PMID- 14699170
TI  - Editorial comment-- finding landmarks for understanding white matter stroke.

PMID- 14699171
TI  - Diffusion-weighted imaging of intravascular clots in cerebral venous thrombosis.
AB  - BACKGROUND AND PURPOSE: Hyperintensities on diffusion-weighted MRI at the site of
      venous occlusion have previously been reported in cerebral venous thrombosis
      (CVT). The frequency of these signal changes according to late venous
      recanalization was not determined yet. METHODS: In a series of 28 patients with
      recent CVT, the frequency of hyperintense signals as seen on diffusion-weighted
      MRI in vein(s) or sinus(es) (HSVdwi) was assessed at the time of diagnosis, as
      was rate of recanalization 2 to 3 months after anticoagulation. RESULTS: HSVdwi
      was detected in 20 occluded vein(s) or sinus(es) in 12 patients (41%) with recent
      CVT. The mean apparent diffusion coefficient measured in 5 patients within HSVdwi
      in the superior sagittal sinus was 4.88+/-1.49x10-4mm2/s. The delay since
      clinical onset was larger in the presence than in the absence of HSVdwi as
      detected at the time of diagnosis. No HSVdwi was visible at the second MRI
      although some vessels remained occluded. Complete recanalization of the vessel
      was less frequent when HSVdwi was observed on the first MRI (35% versus 88%,
      P=0.005). CONCLUSIONS: Results of this study suggest that the movements of water
      molecules are more or less restricted within the venous clot according to the
      stage of thrombus formation in CVT. The presence of HSVdwi in occluded veins at
      the time of diagnosis might be predictive of a low rate of vessel recanalization
      2 or 3 months later.

PMID- 14699175
TI  - Superiority of pentobarbital versus chloral hydrate for sedation in infants
      during imaging.
AB  - PURPOSE: To compare the effectiveness and safety of oral pentobarbital and oral
      chloral hydrate for sedation in infants younger than 1 year during magnetic
      resonance (MR) imaging and computed tomography (CT). MATERIALS AND METHODS: A
      computerized database was used to collect information about all cases in which
      sedation was used. Outcomes of all infants who received oral pentobarbital or
      oral chloral hydrate for sedation between 1997 and 2002 were reviewed. Two study
      groups were compared for sedation and discharge times by using Student t test and
      for adverse events by using Fisher exact test and multiple logistic regression
      analysis. RESULTS: Infants (n = 1,316) received an oral medication for sedation.
      Mean doses were 50 mg/kg chloral hydrate and 4 mg/kg pentobarbital. Student t
      test demonstrated no difference in mean time to sedation and in time to discharge
      between groups. Overall adverse event rate during sedation was lower with
      pentobarbital (0.5%) than with chloral hydrate (2.7%) (P <.001). There were fewer
      episodes of oxygen desaturation with pentobarbital (0.2%) than with chloral
      hydrate (1.6%) (P <.01). Both medications were equally effective in providing
      successful sedation. CONCLUSION: Although oral pentobarbital and oral chloral
      hydrate are equally effective, the incidence of adverse events with pentobarbital
      was significantly reduced.

PMID- 14699176
TI  - Detection of clinically unexpected malignant and premalignant tumors with whole
      body FDG PET: histopathologic comparison.
AB  - PURPOSE: To determine the clinical importance and malignant potential of
      unexpected abnormal foci of hypermetabolism at fluorodeoxyglucose (FDG) positron
      emission tomography (PET) performed for evaluation of malignancy. MATERIALS AND
      METHODS: A total of 1,750 FDG PET scans were obtained to evaluate a variety of
      known or suspected malignancies. Each scan was evaluated for abnormal unexpected
      hypermetabolism based on unusual location (ie, foci that did not conform to the
      usual distribution of metastases given the primary tumor for which the PET scan
      was requested) and discrete focal nature of an abnormality. Unexpected findings
      were followed by pathologic confirmation and were considered clinically important
      if the final pathologic diagnosis was cancerous, precancerous, or noncancerous
      but had the potential for local destruction or systemic physiologic effects.
      RESULTS: On the basis of the normal spread pattern of the primary lesion, 58
      abnormal unexpected foci of hypermetabolism were identified in 53 patients. Forty
      five of these abnormalities were followed up with computed tomography (CT),
      magnetic resonance imaging, and/or mammography, and 42 had subsequent tissue
      confirmation at endoscopic, CT-guided, or surgical biopsy. Of 42
      histopathologically confirmed abnormalities, 30 (71%) were either malignant or
      premalignant tumors that differed from the cancer for which the patient was
      originally scanned. Nine other suspicious abnormal foci proved benign and three
      represented false-positive findings, with no abnormal findings at endoscopy.
      Three of nine nonmalignant lesions were considered clinically important because
      of the potential for local destruction and/or systemic effects. CONCLUSION: The
      identification of unexpected foci of hypermetabolism at whole-body FDG PET may
      signal the presence of tumors that are unrelated to the neoplasm for which the
      patient was scanned. Findings of this study emphasize the need for follow-up of
      these abnormalities because the majority represent either malignant or
      premalignant neoplasms, which were not clinically apparent.

PMID- 14699177
TI  - Detection of intracranial aneurysms: multi-detector row CT angiography compared
      with DSA.
AB  - PURPOSE: To prospectively compare the effectiveness of multi-detector row
      computed tomographic (CT) angiography with that of conventional intraarterial
      digital subtraction angiography (DSA) used to detect intracranial aneurysms in
      patients with nontraumatic acute subarachnoid hemorrhage. MATERIALS AND METHODS:
      Thirty-five consecutive adult patients with acute subarachnoid hemorrhage were
      recruited into the institutional review board-approved study and gave informed
      consent. All patients underwent both multi-detector row CT angiography and DSA no
      more than 12 hours apart. CT angiography was performed with a multi-detector row
      scanner (four detector rows) by using collimation of 1.25 mm and pitch of 3.
      Images were interpreted at computer workstations in a blinded fashion. Two
      radiologists independently reviewed the CT images, and two other radiologists
      independently reviewed the DSA images. The presence and location of aneurysms
      were rated on a five-point scale for certainty. Sensitivity and specificity were
      calculated independently for image interpretation performed by the two CT image
      readers and the second DSA image reader by using the first DSA reader's
      interpretation as the reference standard. RESULTS: A total of 26 aneurysms were
      detected at DSA in 21 patients, and no aneurysms were detected in 14 patients.
      Sensitivity and specificity for CT angiography were, respectively, 90% and 93%
      for reader 1 and 81% and 93% for reader 2. The mean diameter of aneurysms
      detected on CT angiographic images was 4.4 mm, and the smallest aneurysm detected
      was 2.2 mm in diameter. Aneurysms that were missed at initial interpretation of
      CT angiographic images were identified at retrospective reading. CONCLUSION:
      Multi-detector row CT angiography has high sensitivity and specificity for
      detection of intracranial aneurysms, including small aneurysms, in patients with
      nontraumatic acute subarachnoid hemorrhage.

PMID- 14699178
TI  - Breast sentinel lymph node mapping at CT lymphography with iopamidol: preliminary
      experience.
AB  - PURPOSE: To evaluate sentinel lymph node (SLN) mapping with interstitial computed
      tomographic (CT) lymphography with small volumes of iopamidol for direction of
      SLN biopsy in breast cancer. MATERIALS AND METHODS: Thin-section transverse and
      three-dimensional CT images that included the breast and axilla were acquired at
      multi-detector row helical CT in 17 patients with operable breast cancer before
      subcutaneous injection of 2 mL of undiluted iopamidol into peritumoral and
      periareolar areas and 1-5 minutes after massage of injection sites. Location and
      size of SLNs were assessed at CT lymphography and were compared with SLNs at
      standard axillary lymph node dissection with blue dye staining. RESULTS: CT
      lymphography allowed localization of SLNs in all patients by means of
      visualization of a direct connection between an SLN and its afferent lymphatic
      vessels draining from the injection sites. Afferent vessels were joined and
      drained into a single axillary SLN, except in four patients with two or three
      SLNs, including a parasternal one. SLNs did not enhance because of rerouting of
      lymph flow in four patients. At surgery, SLNs that were stained or not stained
      with blue dye were easily found with CT lymphographic guidance. Tumoral
      infiltration was not evident in any resected nodes, except for infiltration in
      one patient with micrometastasis in SLN alone and infiltration in four patients
      with massive metastasis in both SLN and distant nodes. CONCLUSION: Because
      preoperative CT lymphography-guided SLN mapping provides SLN position with
      detailed lymphatic anatomy, it may be useful for the direction of breast SLN
      biopsy.

PMID- 14699179
TI  - Bell palsy: quantitative analysis of MR imaging data as a method of predicting
      outcome.
AB  - PURPOSE: To assess the prognostic value of quantitative analyses of region-of
      interest (ROI) magnetic resonance (MR) imaging data in patients with acute facial
      nerve palsy. MATERIALS AND METHODS: In a single-blinded study, MR images were
      obtained in 39 patients (32 men and seven women; age range, 18-75 years; average
      age, 37.9 years) with acute facial nerve palsy. MR images were obtained before
      the 6th day of illness, on the first day of standard inpatient treatment with
      high-dose steroids. Signal intensity (SI) was measured at ROIs in each of five
      segments (internal auditory canal [IAC]; geniculate ganglion; and labyrinth,
      tympanic, and mastoid segments) of the intratemporal portion of the facial nerve
      and quantitatively analyzed. The SI measurements in the five segments were summed
      and divided by 100 to provide a basis for establishing an MR imaging index. SI
      increases and MR imaging indexes were compared with available clinical findings
      and electrophysiologic data. RESULTS: Data for all 39 patients could be analyzed.
      The MR imaging index was significantly higher in patients with poor outcomes than
      in patients with favorable outcomes (specificity, 97%; sensitivity, 75%; P <.01).
      The SI increases in the IAC were significantly different between patients who
      progressed to full recovery (mean increase, 45.7%) and patients who developed
      chronic facial paralysis (mean increase, 156.5%) (sensitivity, 100%; specificity,
      97%; P <.001). The results of differentiating between patients with good and
      those with poor outcomes on the basis of SI measurements in the IAC were found to
      be in complete agreement with electrophysiologic data. CONCLUSION: Quantitative
      analysis of ROI MR imaging data is a valid method of predicting the outcome of
      acute facial nerve palsy during the first days after onset of symptoms and thus
      at a time when it is not yet possible to obtain valuable prognostic information
      by using electrophysiologic methods.

PMID- 14699180
TI  - Living donor liver transplantation: complications in donors and interventional
      management.
AB  - PURPOSE: To evaluate the incidence of postoperative complications in liver donors
      and the efficacy of interventional management for treating these complications.
      MATERIALS AND METHODS: The study included 386 consecutive donors: 219 donors
      underwent right lobectomy or segmentectomy and 167 donors underwent left
      lobectomy or segmentectomy. Postoperative status, laboratory data, and radiologic
      images were reviewed for postoperative complications. Interventional management
      consisted of percutaneous drainage, ultrasonographic (US)-guided aspiration,
      percutaneous transhepatic biliary drainage (PTBD) and balloon dilation,
      transcatheter arterial embolization, or portal vein stent placement. Technical
      success, clinical improvement, and complications were documented following
      intervention. RESULTS: In 52 (13.5%) donors, 56 postoperative complications were
      encountered, including pleural effusion (n = 9), biliary leakage (n = 6), biliary
      obstruction (n = 5), intraperitoneal abscess (n = 5), active bleeding (n = 5),
      portal vein stenosis or kink (n = 3), biloma (n = 2), and other complications (n
      = 21). Complications occurred in 41 (18.9%) right lobe and 11 (7.0%) left lobe
      donors (P <.001). Twenty-seven (48%) complications were treated with
      interventional management (percutaneous drainage, n = 10; US-guided aspiration, n
      = 6; PTBD and balloon dilation, n = 4; transcatheter arterial embolization, n =
      4; and stent placement, n = 3) and resolved completely. No procedure-related
      complications occurred. In one donor with venous oozing, arteriographic images
      did not show an active bleeding focus; thus, bleeding control with interventional
      management failed. The remaining 29 complications were treated using medical (n =
      27) or surgical (n = 2) management. One donor with acute renal failure has thus
      far been treated with hemodialysis. CONCLUSION: Although complications from liver
      donation are not uncommon, most are minor and, with medical or interventional
      management, have no long-term sequelae. Interventional management seems useful in
      the treatment of postoperative complications of liver donation.

PMID- 14699181
TI  - Brain abscesses: etiologic categorization with in vivo proton MR spectroscopy.
AB  - PURPOSE: To compare the metabolite patterns observed at in vivo proton magnetic
      resonance (MR) spectroscopy of brain abscesses in patients for whom bacteriologic
      information was obtained from cultures and to categorize the MR spectral patterns
      with respect to the underlying etiologic agents. MATERIALS AND METHODS: MR
      imaging and in vivo single-voxel proton MR spectroscopic data obtained from 75
      patients with brain abscesses were retrospectively analyzed. Ex vivo
      spectroscopic experiments with the pus from 45 of these patients also were
      performed, and the data were further categorized on the basis of bacteriologic
      information. Quantification of various metabolites and metabolite ratios and
      statistical analyses of lactate and lactate/amino acid (AA) ratio levels were
      performed by using one-way analysis of variance. RESULTS: On the basis of in vivo
      proton MR spectroscopic and bacteriologic analysis findings, data were classified
      into three categories: Group 1 data showed resonances of lactate, AAs, and
      acetate, with or without succinate at proton MR spectroscopy; cultures for this
      group showed obligate anaerobes or a mixture of obligate and facultative
      anaerobes. The metabolite patterns in the group 2 and group 3 data were similar
      to the pattern of the group 1 data, with the exception that acetate and succinate
      resonances were absent. Culture was positive for either obligate aerobes or
      facultative anaerobes in group 2 and was sterile in group 3. At analysis of
      variance, in vivo data showed significant differences in lactate/AA ratios (P
      =.008), and ex vivo data showed significant differences in lactate levels (P
      =.001) among the three groups. CONCLUSION: It is possible to differentiate
      anaerobic from aerobic or sterile brain abscesses on the basis of metabolite
      patterns observed at in vivo proton MR spectroscopy. This information may be
      useful in facilitating prompt and appropriate treatment of patients with these
      abscesses.

PMID- 14699182
TI  - Accurate quantification of right ventricular mass at MR imaging by using cine
      true fast imaging with steady-state precession: study in dogs.
AB  - PURPOSE: To assess the accuracy of cine magnetic resonance (MR) imaging with a
      segmented true fast imaging with steady-state precession (FISP) technique for
      right ventricular (RV) mass quantification. MATERIALS AND METHODS: Fourteen dogs
      were imaged with a 1.5-T clinical MR imaging unit by using an
      electrocardiographically gated true FISP sequence. Contiguous segmented k-space
      cine images were acquired from the base of the RV to the apex during suspended
      respiration (repetition time msec/echo time msec, 3.2/1.6; section thickness, 5
      mm; in-plane resolution, 1.0 x 1.3 mm2). After imaging, each dog was sacrificed,
      and the RV free wall was isolated and weighed. Each MR imaging data set was
      analyzed twice by each of two independent observers who were blinded to the
      results of RV mass measurement at autopsy, and the mass measurements at MR
      imaging were compared with the autopsy results by using linear regression and
      Bland-Altman analysis. RESULTS: RV mass measurements calculated by using the true
      FISP cine MR images were nearly identical to those at autopsy (R = 0.82, standard
      error of the estimate = 1.7 g, P >.05), with a mean difference between the
      autopsy and MR imaging measurements of 0.3 g +/- 1.7 (1.9% +/- 8.2) (P >.05).
      Inter- and intraobserver variations were small, with a mean interobserver
      variability of -0.1 g +/- 2.3 and a mean intraobserver variability of 0.2 g +/-
      1.6 at every-section analysis. CONCLUSION: In this animal model, true FISP cine
      MR imaging enabled accurate quantification of RV mass.

PMID- 14699183
TI  - MR image-based grading of lumbar nerve root compromise due to disk herniation:
      reliability study with surgical correlation.
AB  - A system for grading lumbar nerve root compromise (no compromise, contact of disk
      material with nerve root, deviation of nerve root, and compression of nerve root)
      was tested in the interpretation of routine magnetic resonance images of 500
      lumbar nerve roots in 250 symptomatic patients. Intra- and interobserver
      reliability was assessed for three independent observers. In the 94 nerve roots
      evaluated at surgery, surgical grading was correlated with image-based grading.
      kappa statistics indicated substantial agreement between different readings by
      the same observer and between different observers (for intraobserver agreement,
      kappa = 0.72-0.77; for interobserver agreement, kappa = 0.62-0.67). Correlation
      of image-based grading with surgical grading was high (r = 0.86). The image-based
      grading system enabled reliable evaluation and reporting of nerve root
      compromise.

PMID- 14699184
TI  - Shortening MR image acquisition time for volumetric interpolated breath-hold
      examination with a recently developed parallel imaging reconstruction technique:
      clinical feasibility.
AB  - A recently developed parallel magnetic resonance (MR) imaging technique, parallel
      imaging with an augmented radius in k space, was used to accelerate the
      volumetric interpolated breath-hold examination (VIBE) performed in 20 patients
      referred for clinical liver imaging. Nonaccelerated MR images were also acquired
      in these patients. A five-point scale was used to score the quality of the
      images. The acceleration resulted in reduced image quality: The nonaccelerated
      images had a significantly higher (P <.05) mean score--3.8 +/- 0.3 (SD),
      indicating good quality--than the accelerated images--3.0 +/- 0.3, indicating
      acceptable quality. However, for three patients who could not hold their breath
      for the duration necessary for nonaccelerated imaging, less severe breathing
      artifacts on the accelerated images resulted in improved quality compared with
      the quality of the nonaccelerated images. Parallel MR imaging-accelerated VIBE
      may be beneficial for patients who have difficulty sustaining a breath hold for
      the duration necessary to perform nonaccelerated imaging.

PMID- 14699185
TI  - Fetal sheep with tracheal occlusion: monitoring lung development with MR imaging
      and B-mode US.
AB  - PURPOSE: To assess the accuracy of magnetic resonance (MR) imaging in determining
      fetal lung volume (FLV) and to observe fetal lung development with B-mode
      ultrasonography (US) and MR imaging. MATERIALS AND METHODS: Seven sheep fetuses
      between 92 and 141 gestational days (term, 145 days) with and without tracheal
      occlusion (controls) underwent serial MR imaging and US. FLV at MR imaging was
      measured with true fast imaging with steady-state precession in coronal and
      transverse planes. The combined cross-sectional left- and right-lung area was
      measured with US at three transverse levels. FLV was measured at autopsy.
      Statistical evaluations included linear regression analysis and calculation of
      the mean and 95% CI. RESULTS: No differences in FLV were observed on coronal or
      transverse MR images (r2 = 0.98; slope = 0.91; 95% CI: 0.82, 1.01). FLV at MR
      imaging at termination of the experiment was significantly related to FLV at
      autopsy (r2 = 0.96; slope = 1.27; 95% CI: 0.97, 1.57; n = 6). FLV at MR imaging
      increased more rapidly with gestational age in fetuses with tracheal occlusion
      (21.0 mL/d; 95% CI: 10.7, 31.3) than in controls (4.7 mL/d; 95% CI: 1.7, 7.7).
      Increase in left- and right-lung area at US was accelerated in fetuses with
      tracheal occlusion (1.60 cm2/d; 95% CI: 1.3, 1.9) compared with controls (0.38
      cm2/d; 95% CI: 0.23, 0.53). Left- and right-lung area at US and FLV at MR imaging
      were significantly correlated (r2 = 0.82). CONCLUSION: FLV can be measured with
      moderate accuracy at MR imaging on both coronal and transverse images. MR imaging
      and B-mode US are useful tools for monitoring and quantifying tracheal occlusion
      stimulated fetal lung growth in sheep fetuses.

PMID- 14699186
TI  - Left ventricular mass: manual and automatic segmentation of true FISP and FLASH
      cine MR images in dogs and pigs.
AB  - PURPOSE: To evaluate the accuracy of manually and automatically segmented true
      fast imaging with steady-state precession (FISP) and fast low-angle shot (FLASH)
      cine magnetic resonance (MR) imaging in the determination of left ventricular
      (LV) mass. MATERIALS AND METHODS: Nine dogs and five pigs underwent cine MR
      imaging of the entire LV from base to apex. Manual and automatic segmentation
      times were recorded, and LV masses determined with each were compared with each
      other and with the true LV mass at autopsy. Estimated mass and true mass at
      autopsy were compared by calculating the correlation coefficient and the mean
      difference between the two for each MR sequence and segmentation method. RESULTS:
      True LV mass at autopsy correlated well with masses determined with manual and
      automatic contours on true FISP MR images. Mean differences between true LV mass
      and masses determined from manual contours on true FISP and FLASH images were 
      0.8 g +/- 2.6 and 3.7 g +/- 6.8, respectively. When manually drawn end-diastolic
      contours were automatically propagated to end systole, mean differences were 2.0
      g +/- 3.6 (P =.05) and 9.1 g +/- 6.5 (P <.05) for true FISP and FLASH images,
      respectively. For automatic contours, mean differences were 10.6 g +/- 8.5 (P
      <.05) and 27.7 g +/- 13.4 (P <.05) for true FISP and FLASH images, respectively.
      Mean automatic segmentation time was six times less than mean manual segmentation
      time. CONCLUSION: LV mass was determined most accurately by using manual contours
      on true FISP images. In these animal models, fully automatic segmentation of true
      FISP images was performed in one-sixth of the time of manual segmentation and
      yielded LV masses with a mean error of approximately 5% of true LV mass.

PMID- 14699187
TI  - In-stent restenosis limitation with stent-based controlled-release nitric oxide:
      initial results in rabbits.
AB  - PURPOSE: To evaluate effect of controlled stent-based release of an NO donor to
      limit in-stent restenosis in rabbits. MATERIALS AND METHODS: Bioerodable
      microspheres containing NO donor or biodegradable polymer (polylactide-co
      glycolide-polyethylene glycol) were prepared and loaded in channeled stents.
      Daily concentrations of NO release from NO-containing microspheres were assayed
      in vitro. NO- and polymer-containing (control) microsphere-loaded stents were
      deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were
      harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine
      monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear
      antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with
      statistical significance evaluated by using one-way analysis of variance.
      RESULTS: NO-containing microspheres released NO with an initial bolus in the 1st
      week, followed by sustained release for the remaining 3 weeks. Significant
      increase in cGMP levels and decrease in proliferating cell nuclear antigen
      positive cells were found at 7 days for the NO-treated group relative to controls
      (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and
      32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01
      [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/-
      0.08 at 28 days, P <.01). CONCLUSION: Stent-based controlled release of NO donor
      significantly reduces in-stent restenosis and is associated with increase in
      vascular cGMP and suppression of proliferation.

PMID- 14699189
TI  - What is normal? What is sick?

PMID- 14699188
TI  - Carotid arteries: contrast-enhanced US angiography--preliminary clinical
      experience.
AB  - B-mode ultrasonographic (US) angiography enhanced with a microbubble-based US
      contrast agent (FS069) was evaluated in human subjects with carotid artery
      disease. Results at contrast material-enhanced US angiography and duplex US were
      compared with those at conventional angiography. Both US angiography and duplex
      US accurately depicted stenoses of 70% or more compared with those depicted at
      conventional angiography. The percentage diameter stenosis of the internal
      carotid artery measured at US angiography strongly correlated with that measured
      at conventional angiography (r = 0.988). The percentage area stenosis measured at
      US angiography strongly correlated with ex vivo measurements of the resected
      carotid plaque at magnetic resonance imaging (r = 0.979). US angiography depicted
      unsuspected wall irregularities, ulceration, and dissection.

PMID- 14699191
TI  - Datapoints: depression and leaving employment among older adult americans.

PMID- 14699193
TI  - Law & psychiatry: mental illness, police interrogations, and the potential for
      false confession.

PMID- 14699194
TI  - Managed care: improving psychiatric drug benefit management: III. The VA's
      approach to atypical antipsychotics.

PMID- 14699195
TI  - Child & adolescent psychiatry: obtaining child mental health services through
      medicaid: the experience of parents in two states.

PMID- 14699196
TI  - Rehab rounds: enhancing treatment adherence among persons with schizophrenia by
      teaching community reintegration skills.

PMID- 14699197
TI  - Depression and the ability to work.
AB  - OBJECTIVE: Depression can have a serious impact on a person's ability to work.
      The purpose of this study was to describe depressed persons who work and
      depressed persons who do not work and to identify factors related to depressed
      persons' working. METHODS: The combined 1994 and 1995 National Health Interview
      Survey Disability Supplement was used to identify persons aged 18 to 69 with
      depression. Sociodemographic, health, functional, and disability characteristics
      of working depressed persons and nonworking depressed persons were compared with
      use of a chi square test of significance. After adjustment for sociodemographic
      variables, multiple logistic regression analysis was used to identify factors
      associated with work among depressed persons. RESULTS: Approximately half of the
      persons who reported major depression were in the labor force. Compared with
      nonworking depressed persons, working depressed persons tended to be younger, to
      be male, to be better educated, to have a higher income, to live alone or with a
      nonrelative, and to live in an urban or suburban location. They less often
      perceived themselves as unable to work or as disabled and were healthier and less
      impaired by social, cognitive, and physical limitations than their nonworking
      counterparts. After sociodemographic factors were controlled for, health and
      functional characteristics were strongly associated with depressed persons'
      working. CONCLUSIONS: Depressed persons who work and who do not work differed
      across sociodemographic, health, functional, and disability factors.
      Understanding the factors associated with depressed persons' working and not
      working may help policy makers, employers, and clinicians shape health care
      benefits packages, employee assistance programs, disability programs, and
      treatment programs appropriately. In particular, it may be important to focus on
      individuals with depression and comorbid general health conditions.

PMID- 14699198
TI  - Impact of multiple-family groups for outpatients with schizophrenia on
      caregivers' distress and resources.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of multiple
      family group treatment on distress and psychosocial resources among family
      caregivers of persons with schizophrenia. METHODS: A total of 97 consumers with
      schizophrenia or another psychotic disorder and their caregivers were randomly
      assigned to receive multiple-family group treatment (N=53) or standard
      psychiatric outpatient care (N=44). Reliable and valid measures were used to
      assess caregivers' distress, caregivers' resources, and consumers' clinical
      status. RESULTS: After consumers' clinical status and baseline rates of
      caregivers' distress and caregivers' resources were controlled for, the
      caregivers of consumers who received multiple-family group treatment experienced
      greater reductions in distress but no increases in resources compared with
      caregivers of consumers who received standard psychiatric care. CONCLUSIONS:
      Multiple-family group treatment reduced caregivers' distress but did not increase
      caregivers' resources relative to standard psychiatric care.

PMID- 14699199
TI  - Criminal history as a prognostic indicator in the treatment of homeless people
      with severe mental illness.
AB  - OBJECTIVE: This study examined the clinical problems and treatment outcomes of
      homeless people with severe mental illness and a history of incarceration.
      METHODS: Between May 1994 and June 1998, a total of 5,774 people entered
      assertive community treatment case management services in the Access to Community
      Care and Effective Services and Supports (ACCESS) demonstration program at 18
      sites in nine states. This study used data from reassessments at 12 months after
      program entry. Analysis of variance was used to compare baseline status and 12
      month outcomes for clients with a lifetime incarceration history of less than six
      months, of six months or more, and no incarceration history. The outcomes
      assessed were housing status, employment status, psychiatric problems, alcohol
      problems, drug problems, and criminal justice involvement. RESULTS: Two-thirds of
      the ACCESS clients had a history of incarceration, with about one-third having
      less than six months of incarceration and about one-third having six months or
      more of incarceration. Clients with a long-term incarceration history had higher
      psychiatric symptom scores, higher drug use and alcohol use scores, and higher
      levels of dual diagnosis than those with a short-term incarceration history or
      those with no history of incarceration. The same order of differences was found
      on measures of childhood abuse, family-of-origin stability, and childhood conduct
      disorder. Clients with an incarceration history of six months or more reported
      higher levels of long-term homelessness than the group without an incarceration
      history. The group with an incarceration history of less than six months showed
      less improvement at the 12-month follow-up evaluation than the group with no
      incarceration history on only one outcome measure, psychiatric problems. The
      group with an incarceration history of six months or more had poorer outcomes
      than the group with no incarceration history on only two of six outcomes,
      psychiatric problems and number of days in jail. CONCLUSIONS: This study found
      that among homeless clients with severe mental illness, clients with a history of
      incarceration have more serious problems and show somewhat less improvement in
      some community adjustment domains.

PMID- 14699200
TI  - Police officers' attitudes toward and decisions about persons with mental
      illness.
AB  - OBJECTIVE: A significant portion of police work involves contact with persons who
      have mental illness. This study examined how knowledge that a person has a mental
      illness influences police officers' perceptions, attitudes, and responses.
      METHODS: A total of 382 police officers who were taking a variety of in-service
      training courses were randomly assigned one of eight hypothetical vignettes
      describing a person in need of assistance, a victim, a witness, or a suspect who
      either was labeled as having schizophrenia or for whom no information about
      mental was provided. These officers completed measures that evaluated their
      perceptions and attitudes about the person described in the vignette. RESULTS: A
      4 x 2 multivariate analysis of variance (vignette role by label) examining main
      and interaction effects on all subscales of the Attribution Questionnaire (AQ)
      indicated significant main effects for schizophrenia label, vignette role, and
      the interaction between the two. Subsequent univariate analyses of variance
      indicated significant main effects for role on all seven subscales of the AQ and
      for label on all but the anger and credibility subscales. Significant role-by
      label interaction effects were found for the responsibility, pity, and
      credibility subscales. CONCLUSION: Police officers viewed persons with
      schizophrenia as being less responsible for their situation, more worthy of help,
      and more dangerous than persons for whom no mental illness information was
      provided.

PMID- 14699201
TI  - Association between cognitive functioning and employment status of persons with
      bipolar disorder.
AB  - OBJECTIVE: The purpose of this study was to identify variables associated with
      employment status among persons with bipolar disorder, including cognitive
      functioning, severity of symptoms, demographic variables, and variables related
      to course of illness. METHODS: The authors assessed the current employment status
      of 117 persons with bipolar disorder. Study participants' cognitive functioning
      was evaluated with the Repeatable Battery for the Assessment of
      Neuropsychological Status, the information and letter-number sequencing subtests
      of the Wechsler Adult Intelligence Scale III, and part A of the Trail Making
      Test. Symptoms were rated by using the Brief Psychiatric Rating Scale, the
      Hamilton Depression Scale, and the Young Mania Rating Scale. A stepwise
      multivariate logistic regression analysis was used to predict employment status.
      RESULTS: Fifty-one percent of the study participants had no current work
      activity, 21 percent worked part-time or as volunteers, and 27 percent had full
      time competitive employment. Current employment status was significantly
      associated with cognitive performance, especially immediate verbal memory, total
      symptom severity, history of psychiatric hospitalization, and maternal education.
      No association was found between employment status and history of psychotic
      symptoms, number of years of education, or age at onset of illness. CONCLUSIONS:
      Vocational programs for persons with bipolar disorder would benefit from
      inclusion of a formal cognitive assessment to better assess work potential and to
      study the predictors of work-related outcomes.

PMID- 14699202
TI  - Response to vocational rehabilitation during treatment with first- or second
      generation antipsychotics.
AB  - OBJECTIVE: Second-generation antipsychotics may enhance the rehabilitation of
      individuals with schizophrenia. The authors hypothesized that clients receiving
      second-generation antipsychotics would use vocational rehabilitation services
      more effectively and would have better employment outcomes than those receiving
      first-generation antipsychotics. METHODS: Ninety unemployed clients with
      schizophrenia and related disorders who were beginning a vocational
      rehabilitation program were followed for nine months. Three groups were defined
      according to the medication in use at study entry: olanzapine (N=39), risperidone
      (N=27), or first-generation antipsychotics only (N=24). Participants were
      interviewed monthly. RESULTS: The olanzapine and risperidone groups did not
      differ on any employment outcomes. On most vocational indicators, clients
      receiving second-generation agents did not differ from those receiving first
      generation agents. However, at nine months the second-generation group had a
      significantly higher rate of participation in vocational training; a trend was
      found toward a higher rate of paid employment. All groups showed substantial
      improvement in employment outcomes after entering a vocational program.
      CONCLUSIONS: The hypothesis that second-generation antipsychotics promote better
      employment outcomes than first-generation antipsychotics was not upheld. However,
      second-generation agents appear to be associated with increased participation in
      vocational rehabilitation.

PMID- 14699203
TI  - A study of long-stay patients resettled in the community after closure of a
      psychiatric hospital in Italy.
AB  - OBJECTIVE: This study examined the outcomes of all patients who were discharged
      from an Italian psychiatric hospital into community residences three to four
      years after discharge. METHODS: The total population of Antonini Mental Hospital
      near Milan on January 1996 (N=337) was assessed by using the expanded Brief
      Psychiatric Rating Scale and the overall social behavior and social role
      functioning sections of the Disability Assessment Schedule. The hospital closed
      in 1999, and all patients who were resettled in the community were reassessed in
      September 2002. Residential stability, use of inpatient services, and mortality
      were also investigated. RESULTS: Of the 337 patients, 64 died before discharge,
      110 were transferred to nursing homes, and 163 were discharged to the community.
      The follow-up of patients who moved to the community showed no differences in
      psychopathology or social role functioning. In terms of overall social behavior,
      a significant increase was observed in the number of patients with mild or no
      disability, and a corresponding decrease was observed in the number with moderate
      disability. Most patients showed residential stability. The rate of postdischarge
      mortality was low, and there were no deaths due to accident or suicide. The
      number of admissions to acute psychiatric wards was limited. CONCLUSIONS: A
      population characterized by a long history of illness and severe disability
      underwent a radical change in care setting and living arrangement with favorable
      outcomes, as indicated by the absence of adverse events or clinical deterioration
      and by some improvement in social behavior. The results confirm that most long
      stay patients can successfully leave psychiatric hospitals and live in community
      residences.

PMID- 14699204
TI  - Use of mental health services in Chile.
AB  - OBJECTIVE: S: To address the growing burden of mental illness in Latin America, a
      better understanding of mental health service use and barriers to care is needed.
      Although many Latin American countries have nationalized health care systems that
      could potentially improve access to care, significant barriers to care remain.
      The authors report the results of a study examining mental health service
      utilization in the general population of Chile. METHODS: The data were drawn from
      the Chile Psychiatric Prevalence Study, a national household survey of 2,987
      persons aged 15 years and older conducted in 1992-1999. As part of the survey,
      psychiatric diagnoses were obtained by using the Composite International
      Diagnostic Interview, and respondents were asked about their use of general and
      mental health care services in the past six months and about their experience of
      barriers to treatment. RESULTS: More than 44 percent of respondents reported use
      of any health care services in the past six months, and 20 percent reported use
      of mental health services. Of the respondents who met criteria for a psychiatric
      disorder, a large proportion (62 percent) did not receive mental health care.
      Increasing severity of the psychiatric disorder correlated with increasing
      frequency of overall help seeking, but only a small proportion of the respondents
      with a psychiatric disorder sought specialized mental health services. Regional
      disparities and inequities in access to care were found. In addition, indirect
      barriers to mental health care, such as stigma and misconceptions about the
      course of psychiatric disorders, were important deterrents to service
      utilization, particularly among persons with lower socioeconomic status.
      CONCLUSIONS: To reduce the burden of mental illness in Chile, additional efforts
      are needed to address both the direct and the indirect barriers to mental health
      care, including regional inequities in access to care.

PMID- 14699205
TI  - Predicting inpatient length of stay with the expanded version of the Brief
      Psychiatric Rating Scale (version 4.0).
AB  - This study examined whether assessment data from administration of the extended
      version of the Brief Psychiatric Rating Scale (BPRS-E) to state hospital patients
      within 72 hours of their admission could be used to predict length of hospital
      stay. BPRS-E data for 222 first-admission patients, for whom the mean length of
      stay was 118.4+/-88.6 days, were factor analyzed, yielding a model with four
      factors: patient's resistance to treatment, positive symptoms, mood, and negative
      symptoms. Discriminant analysis showed that the negative symptoms factor (blunted
      affect, emotional withdrawal, motor retardation, self-neglect, and
      disorientation) correctly predicted whether length of stay would exceed the mean
      in 94 percent of cases. The findings suggest that the severity of negative
      symptoms can be a useful predictor of length of stay among patients with severe
      and persistent mental illness.

PMID- 14699206
TI  - Correlates of health insurance among persons with schizophrenia in a statewide
      behavioral health care system.
AB  - This study explored the demographic and service use correlates of insurance
      status among 539 persons with schizophrenia-spectrum disorders by using the
      administrative data set of a statewide behavioral health care system. Lack of
      health insurance was prevalent in the sample (20 percent) and was associated with
      younger age, Latino ethnicity, and male sex. Persons who did not have insurance
      were less likely to use a community-based service and more likely to use only
      crisis or emergency services than persons who had public or private insurance.
      The findings are consistent with the results of previous research demonstrating
      that lack of insurance is associated with decreased use of community-based
      services among persons with severe mental illness.

PMID- 14699208
TI  - The role of diagnostic systems in the continued stigmatization of patients with
      opioid dependence.

PMID- 14699207
TI  - Comparison of comorbid physical illnesses among veterans with PTSD and veterans
      with alcohol dependence.
AB  - Posttraumatic stress disorder (PTSD) is associated with high rates of medical
      service use and with self-reported poor health. Male veterans admitted to a
      rehabilitation unit for PTSD (N=55) or alcohol dependence (N=38) were evaluated
      for comorbid psychiatric and medical conditions and health risk factors. Patients
      with PTSD were more likely to have osteoarthritis, diabetes, heart disease,
      comorbid depression, obesity, and elevated lipid levels. These findings suggest
      that there may be a relationship between specific medical conditions, possibly
      mediated by behavioral risk factors, among the aging population of veterans with
      PTSD.

PMID- 14699209
TI  - A role development intervention for persons with schizophrenia.

PMID- 14699210
TI  - The comprehensive Asian preschool services program.

PMID- 14699212
TI  - Inferior ST-segment elevation following transseptal puncture for balloon mitral
      valvuloplasty is atropine-responsive.
AB  - ST-segment elevation in the inferior leads has been previously described
      following transseptal puncture for balloon mitral valvuloplasty. The mechanism,
      however, is obscure, and immediate left and right coronary angiography has not
      suggested that embolism or vascular spasm is the cause. We hypothesized that a
      neurally-mediated mechanism was responsible and have since treated 3 further
      patients with inferior ST-segment elevation following transseptal puncture for
      balloon valvuloplasty with intravenous atropine, with rapid resolution of ST
      segment elevation in each case.

PMID- 14699213
TI  - Puncturing the septum: resurgent technique with inherent risk.

PMID- 14699214
TI  - Immediate and medium-term outcomes following the treatment of very long (> or =50
      mm) chronic total coronary artery occlusions.
AB  - OBJECTIVE: The follow-up patency rates and associated clinical and angiographic
      variables following stenting of very long (> or =50 mm) and chronic (>6 months)
      total coronary artery occlusive lesions are not well documented. The aim of the
      present study was to evaluate the early results and mid-term outcomes following
      angioplasty of such lesions. METHODS: Between January 2000 and June 2002, we
      treated 278 chronic coronary occlusions. Of these, eighty-nine occlusions (89
      patients) were with lesions > or =50 mm long; these patients constituted the
      study population. RESULTS: Mean duration of occlusion was 7 +/- 2 months (range,
      6-13 months). Procedural success was obtained in 81 patients. A total of 211
      coronary stents (2.6 +/- 1.1 stents/patient) were implanted, and mean stent
      length was 59 +/- 9 mm. In 3 patients, TIMI flow 1-2 was observed after stent
      implantation. Thus, the angiographic success was considered to be 78/89 patients
      (87.6%). Periprocedural major adverse cardiac events occurred in 6 patients
      (6.7%). Clinical success was obtained in 74 patients (83%). During a 9.6 +/- 2
      month follow-up, forty-three patients (55.1%) remained angina free, thirty-two
      (41%) had recurrence of angina, three patients (3.9%) had a new myocardial
      infarction and no deaths were reported. Target vessel revascularization was
      required in 34 patients (43.6%). Angiographic follow-up was obtained in 70
      patients (90%) at a mean of 7.4 +/- 2 months. Restenosis was observed in 36
      patients (51%), six of whom had reocclusion. A significant correlation was
      observed between the need for reintervention and stent length (R 0.52), residual
      stenosis (R 0.73) and diabetes mellitus (0.68). CONCLUSION: Although coronary
      artery stenting for very long (> or =50 mm) chronically occlusive lesions is
      feasible, safe and associated with a low incidence of periprocedural adverse
      clinical events, these complex and expensive procedures still have a high 6-month
      restenosis rate. These results might be significantly improved with the advent of
      drug-eluting stents.

PMID- 14699215
TI  - Clinical and angiographic predictors of restenosis following renal artery
      stenting.
AB  - Percutaneous stenting has become the procedure of choice for treatment of
      obstructive atherosclerotic renal artery (RA) disease. Restenosis, however,
      continues to be in the range of 15-25% of treated vessels. In this study,
      clinical and angiographic predictors of restenosis were assessed. Of 132 vessels
      included, fifty-eight were followed for restenosis using duplex Doppler (n=15),
      conventional angiogram (n=33) or multislice computed tomography (CT) angiogram
      (n=10). Fifteen vessels (26%) met the criteria for restenosis (lesion > or =50%
      by conventional or CT angiography or >60% by Doppler) at a follow-up range of 2
      20 months (5% <2 months; 68% 3-12 months; 27% 13-20 months). Cox Regression
      analyses were performed for selected variables. A p-value <0.05 was considered
      statistically significant. History of smoking [odds ratio (OR), 6.6:1; p=0.005]
      and time to evaluate for restenosis were independent predictors of the occurrence
      of restenosis. Also, a high restenosis rate (40%) was seen in vessels < or =4 mm
      in diameter (n=20) in contrast to larger vessels (n=38) >4 mm (18.4%). Although
      statistical significance was not reached (possibly because of the small sample
      size), clinically this is a significant finding. A significant drop in systolic (
      15.6 mmHg) and diastolic (-6.2 mmHg) blood pressures was seen following RA
      stenting with no significant change in the total number of antihypertensives used
      (2.4 versus 2.5 for pre- and post-renal stenting, respectively). CONCLUSION:
      Restenosis occurred in 26% of successfully stented RAs. History of smoking, time
      to evaluate for restenosis and small vessels (< or =4 mm) were predictors of its
      occurrence. Clinically, a significant drop in blood pressure was seen with RA
      stenting without a change in the total number of antihypertensives on follow-up.

PMID- 14699216
TI  - Renal artery intervention: better and worse than you thought!

PMID- 14699217
TI  - Impact of barotrauma on acute and late angiographic and clinical outcomes
      following angioplasty and beta-irradiation of coronary in-stent restenotic
      lesions.
AB  - INTRODUCTION: The aim of this study was to prospectively evaluate the impact of
      different degrees of vessel barotrauma on the acute and 1-year clinical and
      angiographic outcomes of percutaneous coronary intervention (PCI) and adjunctive
      vascular brachytherapy (VBT) with 90Sr/90Y for in-stent restenotic lesions (ISR)
      in 118 patients. METHODS AND RESULTS: Sixty consecutive patients were treated
      according to an aggressive PCI strategy (group 1); fifty-eight were treated non
      aggressively (group 2). Irradiation was performed with a manual afterloader.
      Clinical and angiographic baseline characteristics did not differ between groups.
      Group 1 yielded a higher acute lumen gain (2.3 +/- 1.2 mm versus 1.7 +/- 1.3 mm;
      p=0.005) and a higher prevalence of additional stent implantation (48.3% versus
      22.4%; p=0.003). At follow-up, net gain (1.8 +/- 0.7 mm versus 1.4 +/- 0.8 mm;
      p=0.102) was equalized by a higher late loss in group 1 (0.6 +/- 0.8 mm versus
      0.3 +/- 0.7 mm; p=0.036). Remaining target vessel late loss, due to edge effects,
      was considerably higher in group 1 than in group 2 (0.5 +/- 0.8 mm versus 0.2 +/-
      0.5 mm; p<0.001), leading to a higher rate of binary angiographic restenosis
      (23.3% versus 6.9%; p=0.013) and target vessel revascularization (16.7% versus
      5.2%; p=0.046). After excluding patients who received additional stents, the
      angiographic differences between groups were attenuated. CONCLUSION: Our study
      does not support the use of oversized balloons and high inflation pressures for
      the treatment of ISR when combined with VBT. Additional stent implantation
      combined with VBT carries a high risk of repeat revascularization in the setting
      of ISR and should be avoided.

PMID- 14699219
TI  - Angioplasty in the diabetic patient.
AB  - Patients with diabetes have an increased risk of coronary artery disease, and are
      at an increased risk of mortality and morbidity with coronary revascularization
      procedures. This article provides a review of the currently available information
      on percutaneous coronary intervention (PCI) in the diabetic patient. The
      effectiveness of PCI in diabetes is discussed, and the factors that may influence
      outcomes are explored. Recent developments in PCI procedures, such as stents and
      drug-eluting stents, glycoprotein IIb/IIIa inhibitors and brachytherapy, are
      evaluated in terms of their ability to improve the prognosis in this patient
      group.

PMID- 14699218
TI  - Eptifibatide and risk of bleeding after failed thrombolysis.
AB  - The safety of adjunct eptifibatide in the setting of rescue angioplasty (PTCA)
      with or without stenting after full-dose thrombolytic therapy is not well
      defined. Our study was undertaken to assess the risk of hemorrhagic complications
      following use of eptifibatide in patients undergoing rescue PTCA/stenting
      following failed thrombolysis. Clinical records of 43 consecutive patients (53%
      males) who received eptifibatide during rescue PTCA/stenting following full-dose
      fibrinolytic therapy were reviewed. Data were collected for: timing of rescue
      PTCA following fibrinolytic use; concomitant use of other antiplatelet agents;
      hospital length of stay; in-hospital mortality; and incidence of bleeding
      complications. Bleeding complications were categorized as major or minor
      according to Thrombolysis in Myocardial Infarction (TIMI) study group criteria.
      Overall bleeding complications developed in 13 patients (30%), with 4 patients
      (9%) experiencing major bleeding. Univariate predictors of major bleeding
      complications were: older age; female sex; lower baseline platelet count; and
      time to initiation of eptifibatide following failed thrombolysis. On multivariate
      analysis, the only predictors of bleeding were gender (27% in females versus 3%
      in males; odds ratio, 1.7; 95% confidence interval, 0.1-0.9) and time to
      initiation of eptifibatide following failed thrombolysis (4.6 +/- 2 hours versus
      11 +/- 9 hours; p<0.04; 95% confidence interval, 2.1-11.4). Use of potent
      antiplatelet agents during rescue PTCA/stenting results in an increased risk of
      bleeding. Careful attention to predictors of bleeding and, in particular,
      delaying eptifibatide administration following full-dose fibrinolytic use may
      result in the reduction of major and minor bleeding complications.

PMID- 14699220
TI  - Successful placement of a stent in a previously treated un-stentable vessel
      segment, made possible by the ACS Hi-Torque Wiggle Wire: a case report.

PMID- 14699221
TI  - Should the initiation of antiarrhythmic therapy for atrial fibrillation occur in
      the hospital or out of the hospital?: a review of the literature.
AB  - BACKGROUND: Initiation of antiarrhythmic therapy for atrial fibrillation is a key
      step in the treatment of this disorder. Much controversy remains as to the risks
      and benefits of initiating therapy as an inpatient versus an outpatient.
      OBJECTIVE: To explore the various issues of debate and to determine the
      importance and validity of these various issues when it comes to the evaluation
      of patients for in- versus out-of-hospital initiation of antiarrhythmic therapy
      for atrial fibrillation. METHODS: A MEDLINE search of English language journal
      articles since 1966 and a hand search of bibliographies included in pertinent
      retrieved articles was undertaken. Articles used included review articles,
      retrospective studies, and meta-analyses. RESULTS: The literature is full of
      articles for and against outpatient initiation of antiarrhythmic therapy. One
      side feels that the risks of antiarrhythmic therapy initiation are serious enough
      in all patients and easy enough to reverse or ameliorate if the patient is in the
      safety of the monitored hospital setting. The other side argues that these
      complications are infrequent enough except in certain commonly identifiable
      patients, that not all need hospitalization during antiarrhythmic initiation. The
      issues at the heart of the dispute include: the presence or absence of underlying
      heart disease; the period of monitoring after initiation of therapy; the choice
      of antiarrhythmic agent used; and even the seriousness and prevalence of the
      arrhythmia which can be induced. CONCLUSIONS: The issue of in versus out-of
      hospital initiation of antiarrhythmic therapy for atrial fibrillation remains a
      widely disputed topic. Many factors come under consideration when this topic is
      studied. At present, we recommend that patients with significant structural heart
      disease, conduction disease, and/or QT prolongation be strongly considered for in
      hospital initiation of antiarrhythmic medications. Further prospective studies
      are necessary to assess the magnitude of the difference of initiating
      antiarrhythmic therapy as an inpatient versus as an outpatient.

PMID- 14699222
TI  - Successful thrombolysis of acute left atrial thrombi in two pediatric patients
      following interventional cardiac catheterization.
AB  - Acute left atrial intracardiac thrombi require aggressive therapy due to the risk
      of embolization and cerebrovascular accidents. Current treatment includes the use
      of high-dose recombinant tissue plasminogen activator (rTPA), which is associated
      with significant bleeding complications. We report the successful treatment of
      two pediatric patients with acute left atrial thrombi following interventional
      cardiac catheterizations using low-dose rTPA. Echocardiography was used to
      document the presence of the thrombi and monitor treatment with rTPA infusion at
      0.03 mg/kg/hour and heparin. Both patients experienced complete resolution of
      left atrial thrombi without hemodynamically significant side effects. Low-dose
      (0.03 mg/kg/hour) rTPA with heparin is an acceptable and safe alternative to high
      dose rTPA infusion for intracardiac thrombi in children.

PMID- 14699223
TI  - Single coronary artery: a reappraisal.

PMID- 14699224
TI  - A pulmonary embolism treated with the Angiojet technique in a patient with double
      outlet right ventricle.
AB  - A 24-year-old man known to have a double outlet right ventricle, status post
      modified Fontan procedure at age 10, taking coumadin after having a stroke one
      year prior, presented with a massive pulmonary embolism and hemodynamic
      instability. Locally delivered tPA was unsuccessful, and the pulmonary artery
      thrombus was finally removed with a thrombectomy catheter (Angiojet
      thrombectomy); the patient recovered soon thereafter. This is the first report of
      the successful use of a thrombectomy catheter in a patient with pulmonary emboli
      and an occluded Fontan conduit.

PMID- 14699225
TI  - The glucose paradox of cerebral ischaemia.

PMID- 14699226
TI  - Postoperative nausea and vomiting in diagnostic gynaecological laparoscopic
      procedures: comparison of the efficacy of the combination of dexamethasone and
      metoclopramide with that of dexamethasone and ondansetron.
AB  - BACKGROUND AND OBJECTIVE: This study was conducted in a tertiary hospital with
      the aim of comparing the efficacy of a combination of dexamethasone and
      metoclopramide with dexamethasone and ondansetron for the prophylaxis of
      postoperative nausea and vomiting [PONV] after diagnostic gynaecological
      laparoscopic procedures. SUBJECTS AND METHODS: In this prospective, randomised,
      double-blind study, 120 women received either saline I.V. [Group I, n=40]; a
      combination of dexamethasone [8 mg] with metoclopramide [10 mg] [Group II, n=40];
      or a combination of dexamethasone [8 mg] with ondansetron [4 mg] [Group III,
      n=40] prior to induction of general anaesthesia. PONV was evaluated at regular
      intervals. The results were analysed using one-way ANOVA, post-hoc, Chi-square,
      Kruskal-Wallace tests and Z test for proportions where appropriate through a SPSS
      V.9 package. RESULTS: The 3 groups were well matched for demographic
      characteristics. The incidence of nausea and emesis was significantly lower in
      Group III [[17.5%, P <0.02] and [10%, P <0.01] respectively]. Nausea scores were
      also lower in Group III [P <0.02]. Rescue anti-emetic requirements were higher in
      Group I [P <0.05] as compared to Groups II and III. CONCLUSIONS: A combination of
      dexamethasone and ondansetron was more efficacious as compared to that of
      metoclopramide and dexamethasone. The combination of metoclopramide and
      dexamethasone seems to offer no additional benefit as compared to saline placebo.

PMID- 14699227
TI  - The impact of diabetes mellitus on in-hospital stroke mortality.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus is a strong risk factor for stroke.
      However, the prognosis in terms of mortality after a stroke is still unclear,
      especially in diabetic patients. The main purpose of this study was to compare
      and evaluate the features of stroke in patients having diabetes mellitus with
      those without diabetes mellitus and to identify factors that influence survival
      following a stroke. SUBJECTS AND METHODS: In a prospective hospital-based study
      consecutive patients with acute ischaemic stroke were enrolled. A single
      observer, using predefined diagnostic criteria recorded the demographics, risk
      factors and the type of stroke and deaths that occurred during the in-patient
      period. RESULTS: One hundred and sixty-three patients with acute ischaemic stroke
      were enrolled in the study. Type 2 diabetes mellitus was present in 90 (55.2%)
      patients. Diabetes was a significant independent predictor of mortality (OR 4.88;
      95%CI 1.25-19.1). Among the diabetic patients middle cerebral artery (MCA)
      territory infarct (OR 34.8, 95%CI 4.5-269.4) and Glasgow coma score (GCS) less
      than 9 (OR 12.3, 95%CI 3.7-198.1) were independent predictors of mortality.
      CONCLUSIONS: MCA infarcts and poor conscious level increase the mortality in
      diabetic patients with stroke. Mortality is also significantly related to a high
      level of blood glucose at admission.

PMID- 14699228
TI  - The effect of use of pyridostigmine and requirement of vecuronium in patients
      with myasthenia gravis.
AB  - CONTEXT: Patients with myasthenia gravis receive pyridostigmine, an
      anticholinesterase agent, as a part of therapy. These patients demonstrate a
      heightened sensitivity towards non-depolarising muscle relaxants. Continuing
      pyridostigmine till the day of the surgery or omitting it on the night before
      surgery could provide variable results with regards to the effect of vecuronium.
      AIMS: Myographic evaluation of a dose of vecuronium in patients with myasthenia
      gravis on pyridostigmine therapy. SETTING AND DESIGN: A randomised, double-blind,
      clinical study conducted in a teaching hospital. SUBJECTS AND METHODS: Medically
      (oral pyridostigmine) well-controlled adult patients with myasthenia gravis who
      were posted for thymectomy, were randomly divided into two groups. Patients in
      Group 1 received their last dose of pyridostigmine on the night before surgery
      while those in Group 2 received even the morning dose of the drug on the day of
      surgery. Neostigmine (1-2 mg) intravenously was used as rescue medication.
      Vecuronium (0.01 mg/kg) was used for intubation and muscle relaxation during
      trans-sternal thymectomy and its effect was reversed using neostigmine and
      atropine. RESULTS: Fourteen patients (7 in each group) belonging to both sexes
      were enrolled in the study. The intubating dose of vecuronium showed quicker
      onset time (155 sec or 2.7 min approx.) and peak effect (99% T1 suppression) in
      patients belonging to Group 1, and 3/7 (43%) complained of respiratory discomfort
      while waiting for surgery. By giving the morning dose of pyridostigmine (Group
      2), an identical intubating dose of vecuronium showed relative resistance (peak
      effect-97% T1 suppression) and delayed onset time (198 sec approx.). However, the
      reversal was complete at the end of surgery in both the regimens. CONCLUSIONS:
      Omission of the pyridostigmine dose on the day of surgery predisposed patients
      with myasthenia gravis to the possibility of respiratory discomfort and
      sensitivity to vecuronium. Continued administration significantly prolonged the
      onset time of vecuronium and the patients required a higher dose of vecuronium.

PMID- 14699229
TI  - Evaluation of single photon emission computerised tomography (SPECT) using Tc99m
      tetrofosmin as a diagnostic modality for recurrent posterior fossa tumours.
AB  - BACKGROUND: Brain Single Photon Emission Computerised Tomography (SPECT) has been
      established as a potentially useful tool for the assessment of recurrent brain
      tumours. Though brain SPECT is exquisitely sensitive in detecting viable tumour
      tissue in the supratentorial region, its efficacy has not been evaluated till
      date in case of infratentorial posterior fossa tumours. AIM OF THE STUDY: To
      evaluate the diagnostic utility of brain SPECT in differentiating recurrence of
      tumour from post-radiation gliosis in the posterior fossa of the brain. SUBJECTS
      AND METHODS: Twenty-one patients with primary malignant posterior fossa brain
      tumour were evaluated by brain SPECT with Tc99m-Tetrofosmin as the tumour-seeking
      agent. Clinical behaviour of the tumour observed for a minimum period of one year
      after the SPECT study was taken as the gold standard. STATISTICAL ANALYSIS: The
      Chi-square test has been used to note the significance of the association between
      the clinical outcome and the SPECT finding. In addition, the sensitivity and
      specificity of brain SPECT were also calculated. RESULT: Brain SPECT in 4
      patients revealed increased tracer concentration over the primary tumour bed,
      which was consistent with recurrent tumour. The clinical course was consistent
      with tumour recurrence in 13 of the 21 patients, which included 3 patients with
      positive SPECT study and 10 patients with negative SPECT study. Brain SPECT
      revealed recurrent tumour in 4 patients whereas clinical follow-up suggested
      recurrence in 13 patients. The clinical course was consistent with radiation
      necrosis in the remaining 8 patients. In 1 brain SPECT positive patient the
      clinical course was consistent with post-radiation gliosis. CONCLUSION: This
      study demonstrates that brain SPECT is not a sensitive diagnostic modality to
      differentiate recurrent tumour from post-radiation gliosis in the posterior fossa
      of the brain.

PMID- 14699230
TI  - Mycetoma caused by a new red grain mycetoma agent in two members of a family.
AB  - An 18-year-old woman from rural West Bengal was affected with mycetoma involving
      her neck, back, and chest. After an interval of eight years, her younger brother
      developed mycetoma on his left arm. No history of trauma or immune deficiency was
      present in either case. By microscopic examination of sinus-discharged materials
      from both the cases, identical rusty red, hard grains were demonstrated. Soluble
      red pigment-producing colonies grew in Sabouraud dextrose-agar medium. Isolates
      were positive for casein hydrolysis and negative for hydrolysis test of xanthine,
      hypoxanthine, tyrosine, and nitrate reduction. Thus it differed from the only
      known red grain mycetoma agent, Actinomadura pelletieri and was provisionally
      identified as Actinomadura vinacea. Familial affection in mycetoma, that too
      caused by a new agent, is reported here for its uniqueness.

PMID- 14699231
TI  - Buried bumper syndrome with a fatal outcome, presenting early as gastrointestinal
      bleeding after percutaneous endoscopic gastrostomy placement.
AB  - Percutaneous Endoscopic Gastrostomy (PEG) has gained wide acceptance among
      patients who require prolonged tube-feeding support. A rather unusual
      complication of PEG placement is migration of the internal bumper through or into
      the abdominal wall. This was first described in 1988 and is called the buried
      bumper syndrome (BBS). The syndrome is a late complication of PEG tube placement.
      The manifestations of the syndrome must be recognised and the patient referred
      for emergency endoscopy and removal of the bumper. Failure to recognise this
      syndrome may result in serious complications including gastrointestinal bleeding,
      perforation of the stomach, peritonitis and death. We describe a case where a
      patient developed the buried bumper syndrome quite early after PEG placement. The
      syndrome manifested with gastrointestinal bleeding. Although we removed the
      buried bumper endoscopically, and placed another PEG tube, the patient developed
      peritonitis and died 16 hours after the removal of the migrated bumper.

PMID- 14699233
TI  - Digital photography in medicine.

PMID- 14699232
TI  - Olfactory reference syndrome: diagnostic criteria and differential diagnosis.
AB  - Olfactory reference syndrome (ORS) has been defined as a psychiatric condition
      characterized by persistent preoccupation about body odour accompanied by shame,
      embarrassment, significant distress, avoidance behaviour and social isolation.
      ORS has however not been included in the Diagnostic and Statistical Manual of
      Mental Disorders (4th edition) (DSM-IV) and, given that its primary symptoms may
      be found in various other disorders, differential diagnosis can be problematic.
      Using an illustrative case of ORS, we propose diagnostic criteria for ORS. We
      also argue that ORS represents a unique cluster of symptoms that can be
      delineated as a separate diagnostic entity, and that ORS falls on a spectrum of
      social anxiety disorders that includes social anxiety disorder, taijin kyofusho,
      and body dysmorphic disorder.

PMID- 14699234
TI  - Open access to peer-reviewed research through author/institution self-archiving:
      maximizing research impact by maximizing online access.

PMID- 14699235
TI  - Multiple pulmonary infarcts and reversible left ventricular dysfunction in a
      patient with chronic heart disease.

PMID- 14699236
TI  - Images in medicine. Double gibbus due to spinal tuberculosis.

PMID- 14699237
TI  - Images in pathology. Castleman's disease of the parotid.

PMID- 14699238
TI  - Images in radiology. Vein of Galen aneurysmal malformation: antenatal MRI.

PMID- 14699239
TI  - Under-nutrition in older people: a serious and growing global problem!
AB  - Everyone agrees that adequate nutrient intake is important to all living things.
      Without food or water, life on earth would cease to exist. In the field of
      medical health, some gains have been made in meeting maternal and child
      nutritional needs. There is great community awareness regarding the importance of
      meeting the nutritional needs of the developing foetus and child. Malnutrition
      secondary to decreased intake in older people and weight loss is also a serious
      problem with unfortunately, very little notice from the community at large. As
      one ages, several physiological processes may contribute towards the development
      of protein energy malnutrition. Under-nutrition in older people is sadly far too
      common, even in developed countries. It is very likely that the same concerted
      effort used to address child malnutrition is required to combat under-nutrition
      in our elders. Protein energy malnutrition in older people comes at a significant
      cost to the individual, families, communities and the healthcare system. Failure
      to address this syndrome is not only unethical and unhealthy, but also costly.
      Vigilance and community awareness is important in ensuring that this important
      syndrome is detected and managed appropriately. This review mainly attempts to
      describe the pathophysiology, prevalence and consequences of under-nutrition and
      aims to highlight the importance of this clinical syndrome and the recent growth
      in our understanding of the processes behind its development. Some management
      strategies are also briefly described.

PMID- 14699240
TI  - Vulnerable plaques, inflammation and newer imaging modalities.
AB  - Currently, inflammation is considered to be the central player in the
      pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in
      the arterial beds including coronary vasculature. Recent studies using the latest
      imaging techniques have shown that in patients with acute coronary syndromes
      (ACS) multiple plaques are ruptured and have thrombus formation on them. Various
      factors make these plaques unstable, these include structural components of
      plaque like thin fibrous cap, high lipid content of the plaque core and
      inflammation, both localized and generalized. It has been shown that most of the
      ACS are caused by plaques causing non-critical stenosis as seen on traditional X
      ray angiography. Also, the phenomenon of remodelling makes angiography a poor
      technique for plaque visualization. Hence newer modalities are required to
      identify these "vulnerable plaques". Intravascular ultrasound (IVUS),
      thermography and Magnetic Resonance Imaging (MRI) are a few such promising
      techniques. Here we review the invasive and non-invasive modalities that can be
      helpful in the identification of these plaques before they become unstable and
      cause ACS, and also the available therapies to stabilize these plaques.

PMID- 14699241
TI  - Congenital aortic regurgitation due to aortic valvar fenestration with associated
      aortic dissection.

PMID- 14699242
TI  - Cryptococcal lymphadenitis diagnosed by FNAC in a HIV positive individual.

PMID- 14699243
TI  - Theodor E. Kocher (1841-1917): Nobel surgeon of the last century.

PMID- 14699244
TI  - Reboxetine: a novel antidepressant.

PMID- 14699245
TI  - Quantitative stereology: the use of camera lucida for counting neurons by
      physical dissector method in chick brainstem auditory nuclei.

PMID- 14699246
TI  - [The effect of endoscopic sinus surgery on quality of life].
AB  - OBJECTIVES: We assessed the effects of endoscopic sinus surgery on quality of
      life of patients with nasal polyposis or chronic sinusitis. PATIENTS AND METHODS:
      Thirty patients (5 females, 25 males; mean age 36 years; range 17 to 58 years)
      who underwent endoscopic sinus surgery were prospectively evaluated. The
      diagnoses were nasal polyposis in 15 patients and chronic sinusitis in 15
      patients. Primary and revision operations were performed in 23 patients and seven
      patients, respectively. The quality of life was evaluated before and six months
      after surgery with the use of the Chronic Sinusitis Survey (CSS), and Medical
      Outcomes Study Short Form-12 (SF-12). Prior to administration, the two
      questionnaires were translated and adapted to Turkish. Computed tomography (CT)
      findings were scored before and six months after surgery according to the Lund
      Mackay system. The results of the surveys were compared with CT scores. RESULTS:
      The postoperative SF-12 and CSS scores of all the patients improved
      significantly. Computed tomography scores were not found in correlation with
      improvements in the SF-12 and CSS scores. CONCLUSION: Endoscopic sinus surgery
      results in significant improvement in the quality of life of patients with nasal
      polyposis and chronic sinusitis, which may not be reflected by CT scores.

PMID- 14699247
TI  - [Quality of life assessment with the use of the SF-36 in patients with nasal
      polyposis: correlations with clinical and laboratory findings].
AB  - OBJECTIVES: We evaluated the quality of life of patients with nasal polyposis and
      sought correlations between clinical and laboratory parameters and quality of
      life. PATIENTS AND METHODS: Thirty-two patients (8 females, 24 males; mean age 43
      years; range 15 to 68 years) with nasal polyposis were evaluated by history,
      physical examination, endoscopy, computed tomography (CT), nasal smear, and skin
      prick tests. Quality of life was assessed using the Medical Outcomes Study Short
      Form 36 (SF-36). RESULTS: The mean CT score showed a weak correlation with
      symptom and endoscopic scores (p<0.05), whereas the latter two scores were not
      correlated. All the SF-36 scales were adversely influenced, particularly
      including the scores for role limitation caused by emotional problems, general
      perception of health, vitality, and role limitation caused by physical problems.
      An inverse correlation was found between increasing age and complaints of pain
      (p<0.05). Symptom scores were correlated only with role limitation caused by
      emotional problems (p<0.05). Duration of nasal symptoms was correlated with
      increased scores for role limitation caused by physical problems, mental health,
      social functioning, and pain (p<0.05). Computed tomography stage was correlated
      with role limitation caused by emotional problems, pain, and social functioning,
      whereas CT scores showed correlation only with pain (p<0.05). The presence of
      asthma adversely influenced general perception of health scores (p<0.05).
      CONCLUSION: Nasal polyposis adversely affects the quality of life of patients,
      the extent of deterioration being more prominent in certain subscales.

PMID- 14699248
TI  - [The evaluation of thyroid nodules: is routine use of frozen-section examination
      necessary following preoperative fine-needle aspiration biopsy? ].
AB  - OBJECTIVES: We evaluated the role of fine-needle aspiration biopsy as a single
      parameter in determining the extent of thyroidectomy and the necessity of routine
      use of frozen-section examination in patients with nodular thyroid disease.
      PATIENTS AND METHODS: We reviewed 67 patients (40 females, 27 males; mean age 44
      years; range 17 to 78 years) who underwent thyroidectomy for nodular thyroid
      disease. Preoperative fine-needle aspiration biopsy and intraoperative frozen
      section examination were performed in 46 patients and 40 patients, respectively.
      The results were compared with histopathologic diagnoses. RESULTS:
      Histopathologically, 25 patients (37.3%) had malignant and 42 patients (62.7%)
      had benign disease. The sensitivity, specificity, and diagnostic accuracy were
      50%, 95%, and 77% for fine-needle aspiration biopsy, and 100%, 87%, and 91% for
      frozen-section examination, respectively. CONCLUSION: In view of lower
      sensitivity and accuracy rates for fine-needle aspiration biopsy, the routine use
      of frozen-section examination seems to be necessary especially in cases with
      highly suggestive clinical findings of malignancy.

PMID- 14699249
TI  - [Family history, clinical features, and molecular characterization of a patient
      with autosomal recessive non-syndromic hearing loss].
AB  - Autosomal recessive non-syndromic hearing loss is the most common form of
      inherited childhood deafness. Identification of the responsible gene in this type
      of hearing loss presents difficulties because of marked genetic heterogenicity
      and limited clinical presentation. A two-year-old girl was referred to our clinic
      because of congenital hearing loss. Family history showed that her brother and
      six relatives of her parents were also affected by unilateral or bilateral
      hearing loss. There was no consanguinity between the parents, though they were
      from close villages. Audiometric studies revealed severe bilateral sensorineural
      hearing loss. Molecular analysis of the index patient documented that autosomal
      recessive non-syndromic hearing loss resulted from the homozygous 35delG mutation
      in the connexin 26 gene.

PMID- 14699250
TI  - [The value of endoscopy in the diagnosis of rhinolithiasis: a case report].
AB  - Diagnosis of rhinolithiasis may be difficult because of the possibility of
      varying clinical presentations. Complaints of a 34-year-old male patient had been
      misdiagnosed as sinusitis and several plain radiographs had missed the event.
      Endoscopic examination enabled a hard intranasal mass to be seen, resembling a
      rhinolith. The patient's complaints disappeared after endoscopic removal of the
      mass. Failure in the diagnosis was attributed to the presence of superimposed
      adjacent structures on plain films and inadequate exposure of the posteriorly
      located mass by routine anterior rhinoscopy.

PMID- 14699251
TI  - [Current issues on sport SCUBA diving following otosclerosis surgery].

PMID- 14699252
TI  - [Microbiology of the external auditory canal in patients with asteatosis and
      itching].
AB  - OBJECTIVES: We examined the microbiology of the external auditory canal in
      patients with asteatosis and itching and evaluated the efficacy of topical 2%
      alcohol and boric acid solution in patients with normal flora. PATIENTS AND
      METHODS: Bacteriological and mycological cultures were obtained from 76 ears of
      45 patients (36 females, 9 males; mean age 41.8 years; range 17 to 66 years)
      presenting with normal otoscopic findings and no history of ear diseases.
      Treatment protocols were planned according to the culture results. Patients with
      normal flora were administered topical 2% alcohol and boric acid solution to
      relieve itching. RESULTS: Cultures yielded normal flora in 65 ears (85.5%),
      bacterial pathogenic flora in 10 ears (13.1%), and mycosis in one ear (1.3%).
      Complaints of itching decreased significantly following treatment with alcohol
      and boric acid solution in patients with normal flora (p<0.05). No correlation
      was detected between age and the severity of itching (p>0.05). CONCLUSION:
      Despite normal otoscopic findings, external auditory canal cultures may show
      pathogenic colonization in patients with asteatosis. Topical administration of
      alcohol and boric acid solution seems to relieve itching in patients with normal
      flora.

PMID- 14699253
TI  - [The correlation between computed tomography findings of the paranasal sinuses
      and the symptoms of acute sinusitis].
AB  - OBJECTIVES: We investigated the relationship between symptoms, coronal paranasal
      computed tomography (CT) findings and anatomic variations in patients with acute
      sinusitis. PATIENTS AND METHODS: The study included 44 patients (23 females, 21
      males; mean age 35 years; range 21 to 74 years) whose diagnosis was acute
      sinusitis by history and physical examination. A comprehensive inquiry into the
      symptoms was made and coronal paranasal CT scans were obtained in all the
      patients. Correlations were sought between symptom scores, CT scores, and
      anatomic variations. RESULTS: No correlations were found between anatomic
      variations and CT scores. Total symptom scores did not correlate with CT scores.
      A statistically significant correlation existed only between headache and CT
      scores. The most commonly affected sinuses were maxillary sinuses (73%), followed
      by posterior ethmoidal sinuses (60%). CONCLUSION: Our data suggest that routine
      CT evaluations are superfluous in acute sinusitis.

PMID- 14699254
TI  - [Approach to the recurrent laryngeal nerve in thyroid surgery].
AB  - OBJECTIVES: We evaluated our surgical approach to the identification of the
      recurrent laryngeal nerve (RLN) under the guidance of operation microscope and
      RLN dissections during thyroidectomy. PATIENTS AND METHODS: Twenty-three patients
      (20 females, 3 males; mean age 37 years) undergoing thyroidectomy were included
      in the study. Thirty RLN dissections were performed, being unilateral in 16
      patients, and bilateral in seven patients. The recurrent laryngeal nerves were
      identified at the inferior thoracic inlet with the use of the operation
      microscope having an ocular lens of 250 mm, followed by a total dissection up to
      the laryngeal entrance. Endoscopic laryngeal examinations were performed for
      vocal cord movements one day before surgery and postoperatively on days 1, 3, and
      7. RESULTS: No abnormal vocal cord movements were detected preoperatively.
      Following surgery, none of the patients developed persistent RLN paralysis. Two
      patients exhibited transient vocal cord paralysis (limitation in vocal cord
      movements). The use of the operation microscope for RLN dissections resulted in
      prolongation of the operation time ranging from 15 to 40 minutes for each side,
      which tended to decrease with enhanced experience of the surgeon. CONCLUSION: The
      use of the operation microscope enables safe RLN dissections during thyroidectomy
      operations.

PMID- 14699255
TI  - [Palatal pleomorphic adenoma of an unusual size].
AB  - A sixty-year-old male patient presented with complaints of an intraoral mass,
      dysphonia, dysphagia, and snoring. Physical examination revealed a mass of 4 x 4
      cm extending from the hard palate to the oropharynx. Fine needle aspiration
      biopsy showed a benign epithelial lesion. The mass was removed through a
      transoral approach. Histopathologic diagnosis was pleomorphic adenoma. No
      recurrences or surgery-associated complications were observed during a follow-up
      period of a year.

PMID- 14699256
TI  - [The adverse effect of gas formation on prognosis in a patient with deep neck
      infection].
AB  - A seventy-one-year-old woman was hospitalized with a suspicion of deep neck
      infection and poor general health. She had been receiving treatment for
      hepatitis, diabetes mellitus, and cardiac failure and had a history of tooth ache
      and severe neck pain lasting for the past 10 days. She had been admitted to
      another center where she had received antibiotic treatment for five days for
      widespread swelling in the neck and lower extremities, fatigue, and difficulty in
      breathing and swallowing. Upon admission, computed tomography showed gas
      formation in the neck and facial regions. Prompt abscess drainage was performed
      and intense treatment with antibiotics was continued. Despite all efforts, the
      patient died on the second day of hospitalization from cardiopulmonary arrest.
      This case emphasizes how urgent drainage is when gas formation is detected in
      deep neck infections, with inevitable poor prognosis with antibiotic treatment
      alone.

PMID- 14699257
TI  - [The role of inflammation in the etiopathogenesis of nasal polyposis].

PMID- 14699258
TI  - Acanthamoeba sohi, n. sp., a pathogenic Korean isolate YM-4 from a freshwater
      fish.
AB  - A new species of Acanthamoeba was isolated from a freshwater fish in Korea and
      tentatively named Acanthamoeba sp. YM-4 (Korean isolate YM-4). The trophozoites
      were 11.0-23.0 micrometer in length and had hyaline filamentous projections.
      Cysts were similar to those of A. culbertsoni and A. royreba, which were
      previously designated as Acanthamoeba group III. Acanthamoeba YM-4 can survive at
      40 degrees C, and its generation time was 19.6 hr, which was longer than that of
      A. culbertsoni. In terms of the in vitro cytotoxicity of lysates, Acanthamoeba YM
      4 was weaker than A. culbertsoni, but stronger than A. polyphaga. On the basis of
      the mortality of experimentally infected mice, Acanthamoeba YM-4 was found to be
      highly virulent. The isoenzymes profile of Acanthamoeba YM-4 was similar to that
      of A. royreba. An anti-Acanthamoeba YM-4 monoclonal antibody, McAY7, was found to
      react only with Acanthamoeba YM-4, and not with A. culbertsoni. Random amplified
      polymorphic DNA marker analysis and RFLP analysis of mitochondrial DNA and of 18S
      small subunit ribosomal RNA, placed Acanthamoeba YM-4 in a separate cluster on
      the basis of phylogenetic distances. Thus the Acanthamoeba Korean isolate YM-4
      was identified as a new species, and assigned as Acanthamoeba sohi.

PMID- 14699259
TI  - Purification and characterization of a 33 kDa serine protease from Acanthamoeba
      lugdunensis KA/E2 isolated from a Korean keratitis patient.
AB  - In order to evaluate the possible roles of secretory proteases in the
      pathogenesis of amoebic keratitis, we purified and characterized a serine
      protease secreted by Acanthamoeba lugdunensis KA/E2, isolated from a Korean
      keratitis patient. The ammonium sulfate-precipitated culture supernatant of the
      isolate was purified by sequential chromatography on CM-Sepharose, Sephacryl S
      200, and mono Q-anion exchange column. The purified 33 kDa protease had a pH
      optimum of 8.5 and a temperature optimum of 55 degrees C.
      Phenylmethylsulfonylfluoride and 4-(2- Aminoethyl)-benzenesulfonyl-fluoride, both
      serine protease specific inhibitors, inhibited almost completely the activity of
      the 33 kDa protease whereas other classes of inhibitors did not affect its
      activity. The 33 kDa enzyme degraded various extracellular matrix proteins and
      serum proteins. Our results strongly suggest that the 33 kDa serine protease
      secreted from this keratopathogenic Acanthamoeba play important roles in the
      pathogenesis of amoebic keratitis, such as in corneal tissue invasion, immune
      evasion and nutrient uptake.

PMID- 14699260
TI  - Viability of preserved Cryptosporidium baileyi oocysts.
AB  - The present study was undertaken to determine the viability and infectivity of
      oocysts of Cryptosporidium baileyi that had been stored from 1 to 40 months at 4
      degrees C preserved in 2.5% potassium dichromate solution. Oocysts of C. baileyi
      were purified from the feces of experimentally infected chickens using
      discontinuous sucrose gradients. Subsequently, the purified oocysts were
      suspended in 2.5% potassium dichromate solution at a concentration of 1 x 10(7)
      organism/ml, and their viabilities were assessed by nucleic acid staining,
      histologic examination, and infectivity to 2-day-old chickens. All chickens
      inoculated with oocysts that had been stored for 1-18 months developed patent
      infections, while chickens infected with older oocysts remained uninfected.
      Between 5.8% and 82.2% of the oocysts, stored at 4 degrees C in 2.5% potassium
      dichromate solution, were found to be viable, as determined by nucleic acid
      staining. Parasite colonization in the bursa of Fabricius was detected in the
      microvillus border of bursal epithelium. The finding that C. baileyi oocysts
      remain infective to chickens for at least 18 months offers important time-saving
      advantages to investigators who frequently require large numbers of oocysts.

PMID- 14699261
TI  - ELISA detection of vivax malaria with recombinant multiple stage-specific
      antigens and its application to survey of residents in endemic areas.
AB  - An ELISA was developed for the diagnosis of vivax malaria using multiple stage
      specific recombinant antigens of Plasmodium vivax. The DNA from the whole blood
      of a malaria patient was used as template to amplify the coding regions for the
      antigenic domains of circumsporozoite protein (CSP-1), merozoite surface protein
      (MSP-1), apical merozoite antigen (AMA-1), serine repeat antigen (SERA), and
      exported antigen (EXP-1). Each amplified DNA fragment was inserted into pQE30
      plasmid to induce the expression of His-tagged protein in Escherichia coli (M15
      strain) by IPTG. His-tagged proteins were purified by Ni-NTA metal-affinity
      chromatography and used as antigens for ELISA with patient sera that were
      confirmed previously by blood smear examinations. When applied to patient sera,
      122 (80.3%) out of 152 vivax malaria cases reacted to at least one antigen, while
      no reactions were observed with 128 uninfected serum samples. We applied this
      ELISA to the screening of 3,262 civilian residents in endemic regions near the
      DMZ, which resulted in 236 positively detected (7.2%) cases. This method can be
      applied to serological diagnosis and mass screening in endemic regions, or can be
      used as a safety test for transfusion blood in endemic areas.

PMID- 14699262
TI  - Evolutionary course of CsRn1 long-terminal-repeat retrotransposon and its
      heterogeneous integrations into the genome of the liver fluke, Clonorchis
      sinensis.
AB  - The evolutionary course of the CsRn1 long-terminal-repeat (LTR) retrotransposon
      was predicted by conducting a phylogenetic analysis with its paralog LTR
      sequences. Based on the clustering patterns in the phylogenetic tree, multiple
      CsRn1 copies could be grouped into four subsets, which were shown to have
      different integration times. Their differential sequence divergences and
      heterogeneous integration patterns strongly suggested that these subsets appeared
      sequentially in the genome of C. sinensis. Members of recently expanding subset
      showed the lowest level of divergence in their LTR and reverse transcriptase gene
      sequences. They were also shown to be highly polymorphic among individual genomes
      of the trematode. The CsRn1 element exhibited a preference for repetitive, agenic
      chromosomal regions in terms of selecting integration targets. Our results
      suggested that CsRn1 might induce a considerable degree of intergenomic variation
      and, thereby, have influenced the evolution of the C. sinensis genome.

PMID- 14699263
TI  - Divergent long-terminal-repeat retrotransposon families in the genome of
      Paragonimus westermani.
AB  - To gain information on retrotransposons in the genome of Paragonimus westermani,
      PCR was carried out with degenerate primers, specific to protease and reverse
      transcriptase (rt) genes of long-terminal-repeat (LTR) retrotransposons. The PCR
      products were cloned and sequenced, after which 12 different retrotransposon
      related sequences were isolated from the trematode genome. These showed various
      degrees of identity to the polyprotein of divergent retrotransposon families. A
      phylogenetic analysis demonstrated that these sequences could be classified into
      three different families of LTR retrotransposons, namely, Xena, Bel, and Gypsy
      families. Of these, two mRNA transcripts were detected by reverse transcriptase
      PCR, showing that these two elements preserved their mobile activities. The
      genomic distributions of these two sequences were found to be highly repetitive.
      These results suggest that there are diverse retrotransposons including the
      ancient Xena family in the genome of P. westermani, which may have been involved
      in the evolution of the host genome.

PMID- 14699264
TI  - A serologically diagnosed human case of cutaneous larva migrans caused by
      Ancylostoma caninum.
AB  - A 15-year-old boy, who had recently arrived back from a trip to Cambodia for a
      missionary camp, presented with several serpiginous thread-like skin lesions that
      began as small papules on the left upper extremities 2 weeks before his visit to
      Hospital. The skin lesions were pruritic and erythematous, and had migrated to
      the chest and abdomen. The histopathological findings showed only lymphocytic and
      eosinophilic infiltrations in the dermis of the biopsied skin lesion. The
      patient's serum reacted strongly to the Ancylostoma caninum antigen by an ELISA
      method. Therefore, he was diagnosed with cutaneous larva migrans by A. caninum.
      After the oral administration of albendazole and ivermectin, the skin lesions
      resolved without recurrence. This is the first reported case of a cutaneous larva
      migrans caused by Ancylostoma canimum diagnosed serologically using ELISA in
      Korea.

PMID- 14699265
TI  - Strongyloidiasis associated with amebiasis and giardiaisis in an immunocompetent
      boy presented with acute abdomen.
AB  - Strongyloides stercoralis (SS) is an intestinal nematode that is mainly endemic
      in tropical and subtropical regions and sporadic in temperate zones. SS infection
      frequently occurs in people who have hematologic malignancies, HIV infection and
      in individuals undergoing immunosuppressive therapy. In this study, we report a
      12- year-old immunocompetent boy who was admitted to our hospital with acute
      abdomen. Laboratory evaluation showed strongyloidiasis, amebiasis and giardiasis.
      Clinical and laboratory findings immediately improved with albendazole therapy.
      Therefore, when diarrhea with signs of acute abdomen is observed, stool
      examinations should be done for enteroparasitosis. This approach will prevent
      misdiagnosis as acute abdomen. Complete clinical improvement is possible by
      medical therapy without surgical intervention.

PMID- 14699266
TI  - Seroprevalence of antibodies to Neospora caninum in dogs and raccoon dogs in
      Korea.
AB  - Neospora caninum is an important cause of abortion in cattle, and dogs are its
      only known definitive host. Its seroprevalence among domestic urban and rural
      dogs and feral raccoon dogs (Nyctereutes procyonoides koreensis) in Korea was
      studied by indirect fluorescent antibody test (IFAT) and by the neospora
      agglutination test (NAT), respectively. Antibodies to N. caninum were found in
      8.3% of urban dogs and in 21.6% of dogs at dairy farms. Antibody titers ranged
      from 1:50 to 1:400. Antibodies to N. caninum were found in six (23%) of 26
      raccoon dogs. However, the potential role of raccoon dogs as a source of
      horizontal transmission of bovine neosporosis needs further investigation. The
      results of this study suggest that there is a close relationship between N.
      caninum infection among dairy farm dogs and cattle in Korea. This study reports
      for the first time upon the seroprevalence of N. caninum infection in raccoon
      dogs in Korea.

PMID- 14699267
TI  - "I and thou" or "us and them".

PMID- 14699268
TI  - Trunk muscle strength, cross-sectional area, and density in patients with chronic
      low back pain randomized to lumbar fusion or cognitive intervention and
      exercises.
AB  - STUDY DESIGN: A randomized study. OBJECTIVES: To compare muscle strength, cross
      sectional area, and density of the back muscles in two categories of patients
      with chronic low back pain, randomized to either lumbar fusion or cognitive
      intervention and exercises. SUMMARY OF BACKGROUND DATA: In two clinical trials,
      patients with chronic low back pain plus disc degeneration and postlaminectomy
      syndrome, respectively, were randomized to either lumbar fusion or cognitive
      intervention and exercises. We have previously reported that results for the
      primary outcome were similar at the 1-year follow-up examination. METHODS: As the
      treatment alternatives and test procedures were identical, the two trials were
      merged into one. A total of 124 patients 25 to 60 years of age were included.
      Muscle strength, measured by isokinetic test device and by the Biering-Sorensen
      Test, was measured in 112 patients, and the cross-sectional area and density of
      the back muscles were measured in 61 patients at the inclusion and at the 1-year
      follow-up examination. RESULTS: The exercise group performed significantly better
      in muscle strength than did the lumbar fusion group, with the mean difference at
      184 Nm (95% confidence interval, 64-303 Nm; P = 0.003) and for the Biering
      Sorensen Test 21 seconds (95% confidence interval, 6-36 seconds; P = 0.006). The
      density at L3-L4 decreased in the lumbar fusion group but remained unchanged in
      the exercise group. The mean difference was 5.3 HU (95% confidence interval, 1.1
      9.5 HU; P = 0.01). The cross-sectional area was unchanged in both groups.
      CONCLUSIONS: Patients with chronic low back pain who followed cognitive
      intervention and exercise programs improved significantly in muscle strength
      compared with patients who underwent lumbar fusion. In the lumbar fusion group,
      density decreased significantly at L3-L4 compared with the exercise group.

PMID- 14699269
TI  - Prolotherapy injections, saline injections, and exercises for chronic low-back
      pain: a randomized trial.
AB  - OBJECTIVES: To assess the efficacy of a prolotherapy injection and exercise
      protocol in the treatment of chronic nonspecific low back pain. DESIGN:
      Randomized controlled trial with two-by-two factorial design, triple-blinded for
      injection status, and single-blinded for exercise status. SETTING: General
      practice. PARTICIPANTS: One hundred ten participants with nonspecific low-back
      pain of average 14 years duration were randomized to have repeated prolotherapy
      (20% glucose/0.2% lignocaine) or normal saline injections into tender lumbo
      pelvic ligaments and randomized to perform either flexion/extension exercises or
      normal activity over 6 months. MAIN OUTCOME MEASURES: Pain intensity (VAS) and
      disability scores (Roland-Morris) at 2.5, 4, 6, 12, and 24 months. RESULTS:
      Follow-up was achieved in 96% at 12 months and 80% at 2 years. Ligament
      injections, with exercises and with normal activity, resulted in significant and
      sustained reductions in pain and disability throughout the trial, but no
      attributable effect was found for prolotherapy injections over saline injections
      or for exercises over normal activity. At 12 months, the proportions achieving
      more than 50% reduction in pain from baseline by injection group were glucose
      lignocaine: 0.46 versus saline: 0.36. By activity group these proportions were
      exercise: 0.41 versus normal activity: 0.39. Corresponding proportions for >50%
      reduction in disability were glucose-lignocaine: 0.42 versus saline 0.36 and
      exercise: 0.36 versus normal activity: 0.38. There were no between group
      differences in any of the above measures. CONCLUSIONS: In chronic nonspecific low
      back pain, significant and sustained reductions in pain and disability occur with
      ligament injections, irrespective of the solution injected or the concurrent use
      of exercises.

PMID- 14699271
TI  - Effects of nucleus pulposus on nerve root neural activity, mechanosensitivity,
      axonal morphology, and sodium channel expression.
AB  - STUDY DESIGN: This study analyzed the effects of autografted nucleus pulposus on
      nerve root axon morphology, neurophysiologic function, and sodium channel
      expression. OBJECTIVES: To investigate the chronic effects of the epidural
      implantation of nucleus pulposus on nerve root morphology, neural activity,
      ectopic discharge, mechanosensitivity, and sodium channel expression. SUMMARY OF
      BACKGROUND DATA: It has been reported that ectopic discharges were recorded
      antidromically from sural nerve on compressing nucleus pulposus exposed spinal
      nerves. However, it is not clear what the effects of nucleus pulposus are on
      ectopic discharges recorded directly from the spinal nerve roots. It is also not
      clear what the effects of nucleus pulposus are on the threshold pressure to
      provoke ectopic discharges in the spinal nerves. Sodium channel content increases
      in remodeling axons after nerve injury, but it is not clear what the effects of
      nucleus pulposus are on sodium channel expression in spinal nerve. METHODS: Forty
      six male Sprague-Dawley rats were used, 20 in a nucleus pulposus-implanted group,
      18 in a fat-implanted group, and 8 in a normal group. Fresh autografted nucleus
      pulposus or fat tissue was implanted into the dorsal epidural space at the L4-L5
      disc level. On the 7th, 21st, or 42nd day, neurophysiologic recordings were made
      to determine nerve root response to compression. Nerve roots were then harvested
      to determine sodium channel protein concentration and histologic changes in the
      nerve root. The correlations between sodium channel density and neural activity
      and mechanosensitivity of dorsal root were analyzed statistically. RESULTS:
      Ectopic discharge rate was higher in nucleus pulposus 7-day group. Threshold
      pressure to evoke ectopic discharges was lower in the nucleus pulposus 7-day
      group, and higher in the nucleus pulposus 42-day group compared to the normal
      group. Sodium channel protein density increased in the nucleus pulposus 7-day and
      nucleus pulposus 21-day group compared to normal nerve. Sodium channel density
      changes were not correlated to threshold pressure. Ectopic discharge rate
      increased with increase of sodium channel density in the nerve roots. The number
      of axons with neuropathy increased in the nucleus pulposus 7-day and 21-day
      groups. CONCLUSIONS: Acute exposure of nerve root to nucleus pulposus resulted in
      increased number of axons with neuropathy, higher intensity of ectopic discharges
      on compression, and nerve mechanosensitization. Chronic exposure resulted in
      mechanical desensitization. Changes of sodium channel density were correlated to
      ectopic discharge rate.

PMID- 14699272
TI  - Biomechanical evaluation of the Boston brace system for the treatment of
      adolescent idiopathic scoliosis: relationship between strap tension and brace
      interface forces.
AB  - STUDY DESIGN: Prospective study to evaluate the association between strap tension
      and brace interface forces in the treatment of adolescent idiopathic scoliosis
      using the Boston brace system. OBJECTIVES: To determine the strap tension
      associated with optimal brace interface forces. SUMMARY OF BACKGROUND DATA: Trim
      lines, pad placement, and areas of relief for the brace are guided by
      radiographic studies. However, optimal adjustment of strap tension is unclear and
      remains mostly empirical. METHODS: Brace interface forces in all regions of the
      trunk were measured for 41 patients with adolescent idiopathic scoliosis at three
      standardized strap tensions (20 N, 40 N, and 60 N). The brace interface forces
      were assessed using a mat made of force-sensing transducers. Equivalent interface
      pressure for each trunk region was also calculated to estimate the distribution
      of the interface forces. RESULTS: The brace interface forces and the
      corresponding effective areas increased along with the strap tension for all
      patients. For patients with a single right thoracic curve, the interface pressure
      tended to increase with increasing strap tension. This increase was significant
      in the left axillary, right thoracic, right pelvic, and sternal regions. For
      double right thoracic-left lumbar curves, the increase in interface pressure was
      significant in the left axillary, right pelvic, and sternal regions. However,
      most of this increase occurred between 20 N and 40 N of strap tension, with only
      slight increase or even a decrease in interface pressures between 40 N and 60 N.
      CONCLUSIONS: The strap tension should be set as high as possible (up to 60 N) for
      right thoracic curves. For right thoracic-left lumbar curves, the optimal strap
      tension was approximately 40 N. However, clinicians should ensure that the
      prescribed strap tension does not cause excessive skin pressure or affect the
      compliance with the brace. A side opening in the right lumbar area may improve
      the effectiveness of the brace for double right thoracic-left lumbar curves, but
      care must be taken to avoid skin problems at the opening.

PMID- 14699273
TI  - Cervical range of motion associations with subclinical neck pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate associations
      between subclinical neck pain/discomfort, and range of motion and physical
      dimensions of the cervicothoracic spine. SUMMARY OF BACKGROUND DATA: Despite the
      high prevalence of neck problems, few studies are available indicating any
      physical associations with the development of neck pain, or information regarding
      early signs of pathology from neck pain for subjects not in treatment. METHODS:
      Forty healthy volunteers, between 19 and 42 years of age (mean age 28 years),
      were recruited. The dimensions of the cervicothoracic spine measured were as
      follows: spinal posture, active cervical range of motion, and segment length of
      the neck. All measurements were taken twice from each subject by different
      testers, on the same occasion. Cervical muscle endurance was measured by a
      modified Biering-Sorensen Test. Finally, subjects were questioned about any
      recurrent neck pain/discomfort. RESULTS: Fourteen subjects reported experiencing
      low-level neck pain/discomfort on a recurrent basis. Neck muscle endurance time
      (F1,38 = 6.75, P = 0.01) and left rotation end-of-range (F1,38 = 4.56, P = 0.04)
      were found to be significantly lower for subjects with neck pain. Extension end
      of-range showed a group-specific change at retest, increasing for subjects
      without pain, but decreasing for those with neck pain (F1,38 = 4.67, P = 0.04).
      This same group had a greater range of retraction than the asymptomatic group
      (F1,38 = 4.56, P = 0.04). Subjects overall, irrespective of pain classification,
      demonstrated greater left rotation than right rotation (F1,38 = 4.34, P = 0.04)
      and also showed reduced side flexion on the left (F1,38 = 5.10, P = 0.03) and
      right (F1,38 = 5.27, P = 0.03) with repeated measurement. CONCLUSIONS: Between
      groups differences were observed as lower neck muscle endurance time, reduced
      left rotation, relatively reduced extension at second test, but greater range of
      retraction, when the subclinical and normal groups were compared. These data
      suggest that there are early range changes associated with the development of
      neck pain.

PMID- 14699274
TI  - Posterior lumbar interbody fusion using local facet joint autograft and pedicle
      screw fixation.
AB  - STUDY DESIGN: This is a retrospective study of 42 patients having lumbar
      degenerative disease or spondylolytic spondylolisthesis treated by posterior
      lumbar interbody fusion (PLIF) using local autogenous facet joint graft and
      pedicle screw fixation with an average follow-up time of 8.5 years. OBJECTIVES:
      To evaluate the radiographic and clinical results of patients treated with PLIF
      using adjacent facet joint autograft and pedicle screw internal fixation. SUMMARY
      OF BACKGROUND DATA: Some goals of spinal surgery have been achieved by interbody
      arthrodesis using a posterior approach popularized by Cloward. However,
      significant problems including bone graft collapse, resorption, nonunion,
      persistent neurologic compression, and iliac crest donor complication using the
      classic PLIF remain. There are few reports describing the results of a PLIF by
      total facet joint excision. METHODS: Forty-two patients (average, 53.2 years)
      treated at our institution with PLIF by total facetectomy were followed for an
      average period of 8.5 years. The changes in the Japanese Orthopedic Association
      score, the recovery rate, complications, and radiographic findings were
      evaluated. RESULTS: Good radiographic fusion (92.9%) and clinical results
      (postoperative recovery rate of 76% in the Japanese Orthopedic Association score)
      were achieved by PLIF using local facet joint autograft and pedicle screw
      fixation in treating patients with debilitating lumbar degenerative disease. The
      complications related to the operative procedure occurred in three patients of
      delayed union. CONCLUSIONS: For lumbar degenerative diseases with osteophytic
      changes of facet joints, PLIF using pedicle screw fixation and local autogenous
      bones obtained from facet excision may be justified as a treatment opinion. The
      procedure as described offers advantages for spinal surgery when PLIF is
      warranted.

PMID- 14699275
TI  - The rib epiphysis and other growth centers as indicators of the end of spinal
      growth.
AB  - STUDY DESIGN: The association of capping and fusion of the iliac apophysis, and
      closure of the proximal humerus and rib epiphyseal growth plates to the end of
      spinal growth, was evaluated in a cohort of patients with juvenile and adolescent
      idiopathic scoliosis. OBJECTIVES: To determine the association of closure of the
      proximal rib epiphysis growth plate, the proximal humeral epiphyseal growth
      plate, and capping (Risser 4), and fusion (Risser 5) of the iliac apophysis to
      growth cessation in patients with idiopathic scoliosis. SUMMARY OF BACKGROUND
      DATA: Accurate evaluation of remaining spinal growth is the basis of decision
      making in skeletally immature patients with scoliosis. The ossification of the
      iliac apophysis (Risser sign) has been the main indicator used for making this
      determination. The accuracy of this sign has been called into question and may be
      supplemented with data from other growth centers. METHODS: A total of 101
      patients with juvenile or adolescent idiopathic scoliosis undergoing brace
      treatment were followed for a minimum of 2 years following termination of
      bracing. Serial height measurements and evaluation of iliac apophysis
      ossification, proximal humerus, and rib epiphysis growth center closure were
      performed for each patient. RESULTS: The iliac apophysis capped (Risser 4) at a
      mean age of 14.9 years for girls and 16.0 years in boys. Seventy-six of the 101
      patients (75.2%) had further growth after Risser 4 status. The mean growth was
      1.75 cm in the girls and 2.46 cm in the boys. No growth occurred after iliac
      apophysis fusion (Risser 5) or closure of either the rib epiphysis or proximal
      humerus growth plates. CONCLUSIONS: Capping of the iliac apophysis is not the
      final indicator for the end of spinal growth. Other growth centers should be
      evaluated in conjunction with serial height measurements when making decisions on
      the management of the scoliosis patient.

PMID- 14699276
TI  - A prognostic model for the presence of neurogenic lesions in atypical idiopathic
      scoliosis.
AB  - STUDY DESIGN: Consecutive series of patients with idiopathic scoliosis with
      atypical features. OBJECTIVES: The purpose of this study is to define a specific
      yet sensitive set of signs and symptoms to indicate the use of MRI in patients
      with atypical idiopathic scoliosis. Specifically, this study empirically defines
      a new diagnostic test for the presence of neurogenic lesions based on clinical
      and radiologic data and then reports the properties of this test in relation to
      MRI as the gold standard. SUMMARY OF BACKGROUND DATA: The reported prevalence of
      brain stem and spinal cord abnormalities in patients with idiopathic scoliosis
      associated with atypical features varies from 0% to 60%. This wide range most
      likely results from the fact that the samples studied are either not well defined
      or are heterogeneous across studies. Because of these issues, the likelihood of
      neurogenic lesions in atypical idiopathic scoliosis is not known; consequently,
      the decision to order an MRI is controversial.METHODS A total of 1,206 patients
      coded as having idiopathic scoliosis were identified from our institutional
      database. Of these, 72 patients had one or more atypical features: early-onset
      scoliosis, atypical curve, severe curve despite immaturity (>45 degrees ),
      rapidly progressive curve (>1 degrees per month), back pain, headache, or
      neurologic abnormalities on clinical examination. All 72 patients underwent brain
      and spinal cord MRI. Logistic regression was used to determine significant
      predictors of positive MRI and to define the prognostic model. RESULTS: Eleven
      patients (15%) had abnormal findings on MRI. Eight had an Arnold-Chiari type I
      malformation associated with a syrinx; 1 had an Arnold-Chiari type I
      malformation; 1 a syrinx; and 1 a cervical syrinx with a conus lipoma. MRI was
      positive in 5 of 9 patients (55%) with severe curves despite immaturity. Twenty
      patients had one or more abnormal neurologic signs. Of these, 8 (40%) had a
      positive MRI, while only 3 of the 52 patients (6%) with a normal neurologic
      examination (but other atypical features) had a positive MRI. The most predictive
      model included the variables neurologic abnormalities (yes or no) and severe
      curve despite immaturity (yes or no). Using this model, patients with atypical
      characteristics other than severe curvatures or abnormal neurologic
      abnormalities(s) had a 3% probability (95% confidence interval [CI], 1-12%) of
      having a positive MRI; patients with abnormal neurologic change(s), but a
      nonsevere curve, had a 29% probability of a positive MRI (95% CI, 12-53%) and
      patients with severe curves and no neurologic change(s) had a 32% probability of
      positive MRI (95% CI, 8-71%). Patients with both a severe curve and abnormal
      neurologic change(s) had an 86% probability of positive MRI (95% CI, 46-98%).
      Agreement between this test and the MRI was 75%, with a sensitivity of 82% (95%
      CI, 48-97%) and a specificity of 74% (95% CI, 61-83%). CONCLUSIONS: The model
      derived in this study indicates that the probability of neurogenic lesions is
      extremely low in most patients with idiopathic scoliosis with atypical features.
      However, patients with severe curves despite skeletal immaturity and an abnormal
      neurologic examination have a significant probability of neurogenic lesions.
      Therefore, clinical efficiency will be enhanced by narrowing the indications for
      MRI to those patients with these risk factors.

PMID- 14699277
TI  - Protein S-100b for individual prediction of functional outcome in spinal epidural
      empyema.
AB  - STUDY DESIGN: A study correlating protein S-100b serum levels with postoperative
      functional outcome in patients with spinal cord compression resulting from
      epidural empyema. OBJECTIVES: To evaluate the potential value of protein S-100b
      for prediction of individual functional outcome in medullary lesions resulting
      from spinal epidural empyema. SUMMARY OF BACKGROUND DATA: Despite modern medical
      advances, a reliable individual prediction of functional outcome in case of
      spinal epidural empyema is still not possible. METHODS: Forming two outcome
      groups, clinical outcome following surgery was considered to be favorable in case
      of neurologic improvement with preservation or retrieval of walking ability,
      whereas nonimprovement without restoration of gait function was regarded to be
      unfavorable. Venous blood samples for protein S-100b were taken from all patients
      immediately after admission and regularly after operative decompression. Initial
      levels of S-100b were correlated with preoperative degree and duration of
      paresis, and the individual time course of S-100b measurements was correlated
      with clinical outcome. RESULTS: The initial level of protein S-100b is not
      correlated with preoperative degree and duration of paresis or with functional
      outcome. The individual time course of S-100b measurements, however, is different
      in both outcome groups. Levels of protein S-100b that were either always normal
      or that were initially increased but normalized rapidly within 3 days were
      invariably associated with retrieval of gait function, whereas none of those
      patients recovered in whom increased levels of S-100b persisted beyond the third
      postoperative day (P < 0.003). CONCLUSIONS: Protein S-100b might be a promising
      serum marker with prognostic significance in the event of spinal cord compression
      resulting from epidural empyema.

PMID- 14699278
TI  - Volumetric spinal canal intrusion: a comparison between thoracic pedicle screws
      and thoracic hooks.
AB  - STUDY DESIGN: A computer-aided design analysis. OBJECTIVES: To introduce the
      concept of volumetric spinal canal intrusion and report the relative intrusion
      volumes for thoracic pedicle screws compared to thoracic laminar and pedicle
      hooks. SUMMARY OF BACKGROUND DATA: Thoracic pedicle screws are being used more
      frequently; however, there is concern about neurologic risk from medial
      misplacement. The accepted alternative to screws is hooks. Laminar and pedicle
      hooks also have significant obligatory spinal canal intrusion. To date, there
      have been no comparison studies. METHODS: Volumetric analysis of canal intrusion
      of pedicle screws and hooks was performed by computer-aided design CAM. All
      implants were of a single product line by a single manufacturer (CD Horizon M8,
      Medtronic Sofamor Danek). Intrusion of pedicle screws with medial positioning was
      analyzed in 0.5-mm increments, including a calculation of the "screw shadow,"
      representing additional space not available for the spinal cord between screw
      threads and lateral to a medially positioned screw with intrusion greater than
      the screw radius. The length of screw intrusion was determined from postoperative
      CT scans in patients with thoracic pedicle screw instrumentation. All hook styles
      were analyzed. The volume of the footplate in line with the dorsal surface of the
      footplate was considered the intruding volume for laminar hooks, with increasing
      offset in 0.25-mm increments to represent imperfect fit. Half of the volume of
      the footplate was considered to be the intruding volume for pedicle hooks since a
      properly positioned pedicle hook straddles the pedicle. RESULTS: Volumetric
      intrusion for a 4.5-mm screw ranged from 2.2 mm3 (0.5 mm medial perforation) to
      83.4 mm3 (3.0 mm perforation). For a 5.5-mm screw, intrusion volume range was
      from 1.3 mm3 to 83.2 mm3. Accounting for the "screw shadow," the volumetric
      intrusion was 9.83 mm3 to 116.3 mm3 and 10.88 mm3 to 134.89 mm3, respectively.
      Hook volumetric intrusion ranged from 21.15 mm3 for a pediatric narrow-blade
      ramped pedicle hook to 113.9 mm3 for a wide-blade laminar hook with 1.0 mm of
      step-off. CONCLUSIONS: A 4.5-mm or 5.5-mm thoracic pedicle screw must have a
      medial perforation of >or=1.5 mm to have the same volumetric spinal canal
      intrusion as a pediatric narrow-blade pedicle hook, the smallest hook footplate.
      Further, the medial violation must be >3 mm to approach the same volumetric
      intrusion as the largest hook. Accounting for the "screw shadow," a thoracic
      pedicle screw must have a medial perforation of >2 mm to approach the same
      intrusion volume as a standard pedicle hook. In the absence of direct neural
      injury, this explains the clinical finding of medial perforation of up to 4 mm
      without neurologic compromise.

PMID- 14699279
TI  - Predictors of back pain in a general population cohort.
AB  - STUDY DESIGN: The study used longitudinal data from the first and second cycles
      (1994-1995 and 1996-1997) of the Canadian National Population Health Survey.
      OBJECTIVE: Our objective was to derive prediction models for back pain in the
      general male and female household populations. SUMMARY OF BACKGROUND DATA: Little
      is known about the predictors of back pain in the general population. Most
      previous studies focused on specific occupational groups and used a cross
      sectional or case-control design. METHODS: The study cohort consisted of all
      respondents aged 18+ years who reported no back problems in the 1994-1995
      National Population Health Survey cycle (N = 11,063). Potential predictors of
      chronic back pain were classified into nine groups and entered into stepwise
      logistic regression models. Bootstrap methods were used to derive the final
      models and assess their predictive power. RESULTS: The overall incidence of back
      pain was 44.7 per 1,000 person-years and was higher in women (47.0 per 1,000
      person-years) compared with men (42.2 per 1,000 person-years). In men,
      significant predictors of back pain were age (peak effect in 45-64 years),
      height, self-rated health, usual pattern of activity (especially heavy work),
      yard work or gardening (negative association), and general chronic stress. In
      women, significant factors were self-reported restrictions in activity, being
      diagnosed with arthritis, personal stress, and history of psychological trauma in
      childhood or adolescence. CONCLUSIONS: Overall health and psychosocial factors
      are important predictors of back pain in both men and women. Other risk factors
      differ between the two sexes.

PMID- 14699281
TI  - Estimates and patterns of direct health care expenditures among individuals with
      back pain in the United States.
AB  - STUDY DESIGN: Secondary analysis of the 1998 Medical Expenditure Panel Survey.
      OBJECTIVE: To estimate total health care expenditures incurred by individuals
      with back pain in the United States, calculate the incremental expenditures
      attributable to back pain among these individuals, and describe health care
      expenditure patterns of individuals with back pain. SUMMARY OF BACKGROUND DATA:
      There is a lack of updated information on health care expenditures and
      expenditure patterns for individuals with back pain in the United States.
      METHODS: This study used data from the 1998 Medical Expenditure Panel Survey, a
      national survey on health care utilization and expenditures. Total health care
      expenditures and per-capita expenditures among individuals with back pain were
      calculated. Multivariate regression models were used to estimate the incremental
      expenditures attributable to back pain. The expenditure patterns were examined by
      stratifying individuals with back pain by sociodemographic characteristics and
      medical diagnosis, and calculating per-capita expenditures for each stratum.
      RESULTS: In 1998, total health care expenditures incurred by individuals with
      back pain in the United States reached 90.7 billion dollars and total incremental
      expenditures attributable to back pain among these persons were approximately
      26.3 billion dollars. On average, individuals with back pain incurred health care
      expenditures about 60% higher than individuals without back pain (3,498 dollars
      vs. 2,178 dollars). Among back pain individuals, at least 75% of service
      expenditures were attributed to those with top 25% expenditure, and per-capita
      expenditures were generally higher for those who were older, female, white,
      medically insured, or suffered from disc disorders. CONCLUSIONS: Health care
      expenditures for back pain in the United States in 1998 were substantial. The
      expenditures demonstrated wide variations among individuals with different
      clinical, demographic, and socioeconomic characteristics.

PMID- 14699282
TI  - Performance problems of patients with chronic low-back pain and the measurement
      of patient-centered outcome.
AB  - STUDY DESIGN: In a prospective interventional study, problems with performance
      were evaluated in 101 consecutive patients with chronic low-back pain for more
      than 12 months, before and after participation in an outpatient-based
      multidisciplinary pain management program in Mansfield, United Kingdom.
      OBJECTIVES: To describe problems identified as most important by patients with
      chronic low-back pain and to evaluate the Canadian Occupational Performance
      Measure (COPM) as a tool for measuring problem-specific outcomes. SUMMARY OF
      BACKGROUND DATA: Patients with chronic low-back pain report difficulties with a
      variety of activities. The COPM permits the identification and measurement of
      problems of particular concern to the patient. MATERIALS AND METHODS: COPM,
      likert-modified Roland and Morris Disability Questionnaire, Pain Self-Efficacy
      Questionnaire, and 5-minute walk test were administered at baseline, immediately
      after, and 9 months after intervention. Differences and statistical interactions
      were determined by nonparametric tests. RESULTS: Participants identified 60
      different types of problem activity, 45 of which were identified by nine or fewer
      participants. Decreased walking tolerance was the most frequently identified
      problem (56% of participants). Improvements were observed in all outcomes
      following intervention. Approximately one third of participants reported
      improvements two or more COPM units in overall performance and satisfaction with
      their performance at 9 months. Higher reported performance and satisfaction were
      associated with greater self-efficacy. Increased reported walking performance was
      associated with increased observed 5-minute walk distance (R = 0.35, P = 0.02).
      CONCLUSIONS: Patients with chronic low-back pain report problems with diverse
      activities. The COPM provides a patient-centered outcome measure that displays
      good external validity and responsiveness to change when addressing the
      individual's goals.

PMID- 14699283
TI  - Fast development of high intra-abdominal pressure when a trained participant is
      exposed to heavy, sudden trunk loads.
AB  - STUDY DESIGN: This study focused on intra-abdominal pressure (IAP) during sudden
      trunk loads. Ten participants were exposed to heavy, sudden trunk loads as they
      might occur during patient handling. OBJECTIVES: The aim was to study the
      development of intra-abdominal pressure when well-trained participants cope with
      heavy, sudden trunk loads. It is hypothesized that high IAP develops sufficiently
      fast to be present when the large torques act on the low-back structures. SUMMARY
      OF BACKGROUND DATA: Well-trained sportsmen expose themselves to heavy sudden
      loads of the trunk without getting injured, but it is unknown how they cope with
      these loads. Do they use IAP? IAP is believed to play a significant role in spine
      stability, but this has only been documented in experimental studies with light
      trunk loads. MATERIALS AND METHODS: Ten well-trained judo and jujitsu fighters
      were exposed to heavy sudden trunk loads through imitated patient handling
      situations in which the patient fell, and the fighters were to hold the patient
      and prevent the fall. IAP was measured with a catheter in the stomach. Along with
      the IAP measurement, the load on the low back during the patient falls was
      quantified by a three-dimensional dynamic biomechanical calculation of the
      torques and the compression at the L4/L5 joint. RESULTS: High IAP developed
      quickly and timed in relation to the external torque when the fighters were
      exposed to a sudden patient fall. When the trunk load was heavy and sudden, IAP
      was developed to be present at the time when low-back structures had to cope with
      the large load. CONCLUSIONS: High IAP was developed sufficiently fast to be
      present when the low-back structures had to cope with the large torques released
      from the sudden trunk loading.

PMID- 14699284
TI  - Lumbar spine stabilization with a thoracolumbosacral orthosis: evaluation with
      video fluoroscopy.
AB  - STUDY DESIGN: L3-L5 vertebral body motion was tracked fluoroscopically as
      individuals performed flexion-extension movements wearing different
      thoracolumbosacral orthoses (TLSOs). OBJECTIVE: To assess the effect of custom
      fitted TLSOs on lumbar vertebral body motion. SUMMARY OF BACKGROUND DATA: Several
      methods have been used to evaluate dynamic vertebral motion in vivo. Controversy
      remains regarding the utility of a TLSO in decreasing intervertebral motion in
      the lumbar spine. METHODS: Dynamic motion of the vertebral bodies was assessed
      fluoroscopically under four conditions: without a brace, with a custom fitted
      TLSO, with the TLSO and thigh extender at 0 degrees or 15 degrees. Intervertebral
      motion, i.e., the rotation of one vertebral body with respect to the adjacent
      body in the sagittal plane, throughout the flexion-extension cycle was used to
      assess the effect of each condition. RESULTS: The TSLO reduced both the total L3
      L5 range of motion and the intervertebral motion at each individual level. Total
      rotation at L3 with respect to horizontal was reduced from 70 degrees without a
      brace to 50 degrees with a TLSO. Use of the thigh extender provided an additional
      reduction to 10 degrees. There was no difference between the 0 degrees and 15
      degrees settings. Intervertebral motion was reduced by 40% at both L3-L4 and L4
      L5 when comparing no brace to TLSO and an additional 15% when a thigh extender
      was added. CONCLUSIONS: A custom molded TLSO reduces both total L3-L5 motion and
      intervertebral motion in the lower lumbar spine. These effects are enhanced if a
      thigh extender is used.

PMID- 14699285
TI  - Redefining the magnetic resonance imaging reference level for the cerebellar
      tonsil: a study of 170 adolescents with normal versus idiopathic scoliosis.

PMID- 14699286
TI  - Retrograde ejaculation after anterior lumbar interbody fusion.

PMID- 14699287
TI  - Manual therapy and exercise therapy in patients with chronic low back pain: a
      randomized, controlled trial with 1-year follow-up.

PMID- 14699288
TI  - Radiographic changes in the lumbar intervertebral discs and lumbar vertebrae with
      age.

PMID- 14699289
TI  - Congenital formation of an intraspinal osseous vertebral ring causing spinal cord
      compression.
AB  - STUDY DESIGN: A unique case of the congenital formation of an intraspinal osseous
      vertebral ring causing spinal cord compression is reported. OBJECTIVES: To our
      knowledge, such an osseous ring has not yet been described. The authors detail
      the clinical presentation, imaging, and treatment of the intraspinal osseous
      ring. SUMMARY OF BACKGROUND DATA: There are two traditional categories of
      congenital vertebral anomalies, that of failure of formation and of segmentation.
      The authors propose that this ring may not fit into either of these categories
      and may represent a new category of failure of migration. METHODS AND RESULTS:
      Surgical decompression using a costotransversectomy approach was performed.
      Adequate decompression the spinal cord was achieved. Anterior and posterior
      fusions with instrumentation were used to stabilize the spinal cord. CONCLUSIONS:
      An intraspinal osseous vertebral ring is a unique anomaly that, to our knowledge,
      has not been reported to date. The authors discuss the pathology, imaging, and
      treatment of this unique condition.

PMID- 14699290
TI  - Rapid improvement of paraplegia caused by epidural involvements of Burkitt's
      lymphoma with chemotherapy.
AB  - STUDY DESIGN: Case report. OBJECTIVE: The authors present a case of atypical
      Burkitt's lymphoma with multiple epidural involvements. SUMMARY OF BACKGROUND
      DATA: Spinal cord compression in children is an emergency that requires urgent
      attention to minimize neurologic dysfunction. Although it is not life-threatening
      in most patients, cord compression can cause severe neurologic morbidity.
      MATERIALS AND METHODS: Because the patient showed rapid neurologic deterioration,
      we started chemotherapy and high-dose steroids without laminectomy or
      radiotherapy immediately after a tumor biopsy from the left mandible. RESULT: The
      combined therapies were very effective and his neurologic symptoms improved
      immediately. The epidural involved masses disappeared in imaging studies after
      the first course of chemotherapy including methylprednisolone (20 mg/kg per day
      for 3 consecutive days and gradually tapered off over 2 weeks), vincristine (1.5
      mg/m2 per day), cyclophosphamide (2 g/m2 per day for 2 days) and pirarubicin (40
      mg/m2 per day). After completing seven courses of chemotherapy, the patient is
      now fully ambulant. CONCLUSION: Considering the severe late effects of
      laminectomy and radiotherapy, chemotherapy should be considered as a first choice
      of treatment for spinal cord compression caused by malignant lymphoma.

PMID- 14699291
TI  - Cervical epidural abscess after epidural steroid injection.
AB  - STUDY DESIGN: This is a case report of a cervical epidural abscess presenting
      with neurologic deficits after cervical epidural steroid injection. OBJECTIVE: To
      describe the presentation, diagnosis, treatment, and outcome of a rare
      complication of cervical epidural steroid injection. SUMMARY OF BACKGROUND DATA:
      Cervical epidural steroid injections are a commonly used modality in the
      treatment of cervical spine disease. Serious complications from the procedure are
      rare. There is only one previously reported case of cervical epidural abscess
      after cervical epidural injection in the literature. MATERIALS AND METHODS: A
      case of cervical epidural abscess after epidural steroid injection is presented
      and the relevant literature is reviewed. RESULTS: The patient had partial
      recovery of neurologic function within the first 24 hours after decompressive
      laminectomy, irrigation, and debridement. There were no perioperative
      complications. Intraoperative cultures permitted positive identification of the
      infecting organism and appropriate antibiotic selection. At 7-month follow-up,
      there was no recurrence of infection and the patient had recovered baseline
      neurologic function and neck pain status. CONCLUSIONS: Cervical epidural abscess
      is a rare but potentially devastating complication after epidural steroid
      injection. Neurologic compromise may occur. Timely diagnosis and appropriate
      treatment may result in good clinical outcomes.

PMID- 14699292
TI  - Surgical strategy for cervical dumbbell tumors based on a three-dimensional
      classification.
AB  - STUDY DESIGN: Forty-two patients with cervical dumbbell tumors were analyzed
      retrospectively using a new three-dimensional classification. OBJECTIVES: To
      establish optimal surgical strategies, we considered shapes and three-dimensional
      locations of cervical dumbbell tumors based on diagnostic images and
      intraoperative findings. SUMMARY OF BACKGROUND DATA: Eden's classification for
      dumbbell tumors of the spine, long considered a "gold standard," no longer is
      sufficient to determine surgical strategy in view of recent advances in computed
      tomography and magnetic resonance imaging. METHODS: Forty-two cervical dumbbell
      tumors were characterized according to transverse-section images (Toyama
      classification; nine types) and craniocaudal extent of intervertebral and
      transverse foraminal involvement (IF and TF staging; three stages each). RESULTS:
      Type IIIa tumors, involving dura plus an intervertebral foramen, accounted for
      50% of cases. A posterior approach was used in 35 patients; 7 others underwent a
      combined anterior and posterior approach. A posterior approach was used for all
      type IIa and IIIa tumors, and for some type IIIb (upper cervical), IV, and VI
      tumors; a combined posterior and anterior approach was used for type IIb and the
      remainder of type IV and VI. Reconstruction was performed using spinal
      instrumentation in 4 patients (9.5%). Resection was subtotal in 6 patients
      (14.3%) and total in 36 (85.7%). CONCLUSIONS: Systematic, imaging-based three
      dimensional characterization of shape and location of cervical dumbbell tumors is
      essential for planning optimal surgery. The classification used here fulfills
      this need.

PMID- 14699293
TI  - Iatrogenic intraspinal epidermoid tumor: two cases and a review of the
      literature.
AB  - STUDY DESIGN: Two cases of patients whom intraspinal epidermoid tumors presented
      and were successfully removed 6 years after neonatal lumbar puncture are
      reported. OBJECTIVE: To describe the presentation of this type of spinal tumor
      and strategies for diagnosis and treatment. SUMMARY OF BACKGROUND DATA: Cells
      iatrogenically implanted into the spinal canal during lumbar puncture can slowly
      grow until symptomatic. Diagnosis can be difficult and is often delayed. MRI
      appears to offer some advantages in diagnosis provided that gadolinium is used.
      Treatment is by surgical excision. METHODS: The first patient, a 6-year-old boy,
      presented with severe episodic hip pain of unknown etiology. MRI of the lumbar
      spine revealed a 1-cm epidermoid at L1-L2. The second child, a 6-year-old girl,
      presented with low back pain and dragging of the feet. MRI revealed a mass at L3.
      RESULTS: In both cases, complete excision via lumbar laminectomy was performed.
      Both patients were asymptomatic at the 1-year follow-up with resolution of
      preoperative weakness. CONCLUSIONS: This study highlights an uncommon but not
      rare tumor that may present to the spine specialist in a variety of ways. The
      diagnosis is often delayed. The advent of MRI has improved the ease and accuracy
      of diagnosis. Complete excision is usually possible and is curative.

PMID- 14699294
TI  - [Lung cancer and pollution].
AB  - Active smoking remains the main cause of lung cancer. However, one must not
      neglect the role of occupational exposure, mainly in males and also the role of
      pollution. In non-smoking females of countries like China, pollution due to the
      use of charcoal for cooking may represent the main cause for lung cancer. Outside
      pollution is mainly due to combustion of fossil fuels and to diesel exhaust.
      Inside pollution is mainly due to environmental tobacco exposure and radon in
      western countries whereas in developing countries it is mainly due to cooking
      methods.

PMID- 14699295
TI  - [Cystic adenoid carcinoma of the trachea].
AB  - Cystic adenoid carcinoma (CAC) of the trachea, also called cylindroma, is a rare
      malignant tumor accounting for 1 per thousand of all respiratory tract cancers.
      We report three cases of cylindroma in patients hospitalized for inspiratory
      dyspnea due to a tracheal tumor. Bronchoscopy using a rigid tube revealed a
      smooth tumor of the trachea. Pathology analysis of the biopsy specimen diagnosed
      CAC. The three patients underwent resection with end-to-end anastomosis. Adjuvant
      radiotherapy was given in one patient. The short-term outcome was good but one
      patient developed local recurrence and lung metastasis at six years.

PMID- 14699296
TI  - [Miliary pulmonary tuberculosis following intravesical BCG-therapy].
AB  - A patient given intravesical BCG immunotherapy developed miliary pulmonary
      tuberculosis. After resection of a superficial bladder tumor, the patient was
      given weekly intravesical BCG infusions. After the 4th session, the patient
      developed fever (40 degrees C), shivers, dry cough, profuse sweating, and weight
      loss. Initially, the chest x-ray was normal. The patient was given isoniazid (5
      mg/kg) in a single-drug regimen. Rapid degradation of the general status led to a
      new chest x-ray, 10 days later, which demonstrated a reticulonodular syndrome.
      High-resolution thoracic CT confirmed the diagnosis of miliary pulmonary
      tuberculosis. A three-drug antituberculosis regimen associated with
      corticosteroids was followed by restoration of the general status.
      Antituberculosis therapy was continued for 9 months. The 9-month thoracic CT
      revealed a smaller number of micronodules in the pulmonary parenchyma. This case
      illustrates the discussion concerning the appropriate treatment for patients who
      develop a systemic infection after intravesical BCG-therapy.

PMID- 14699297
TI  - [A rare complication of chronic pancreatitis: pancreatico-pleural fistula].
AB  - Pleural effusion is a rare complication of chronic pancreatitis. We report a case
      observed in a 39-year-old patient hospitalized for dyspnea and pain in the lower
      left thorax. Chest x-ray revealed left pleural effusion. The exudative pleural
      fluid contained a very high amylase level. CT-scan revealed a pseudo-cyst of the
      tail of the pancreas extending into contact with the diaphragm and the chronic
      pancreatitis lesions. Medical treatment associating thoracic drainage,
      somatostatin analog, and antibiotics was unsuccessful. Thoracoscopic pleural
      decortication was performed. The patient then developed pneumonia involving the
      left base. A new antibiotic regimen was delivered and the pseudocyst was drained
      percutaneously under CT guidance. The clinical course was favorable at six months
      with partial involution of the pseudocyst and regression of the pulmonary images.

PMID- 14699298
TI  - [Streptococcus pneumoniae purulent pleurisy and hemolytic uremic syndrome. A case
      report].
AB  - A 22-month-old infant developed purulent pleurisy caused by Streptococcus
      pneumoniae and a hemolytic uremic syndrome. The diagnosis was suggested by the
      classical triad: hemolytic anemia, renal failure and thrombocytemia confirmed by
      renal biopsy which demonstrated extensive cortical necrosis. Renal involvement
      was severe, justifying an indication for renal transplantation.

PMID- 14699299
TI  - [Thymoma and autoimmune thyroiditis. A case report].
AB  - We report an association between a thymus tumor and autoimmune thyroiditis. This
      association is probably related to loss of immune control secondary to loss of
      thymus integrity. A 48-year-old woman was hospitalized for thoracic pain. Her
      past history included thyroiditis treated by L-thyroxin for two years. The chest
      x-ray demonstrated a mediastinal opacity which was confirmed by computed
      tomography. Surgical resection was performed and histological analysis of the
      surgical specimen confirmed the diagnosis of lympho-epithelial thymoma. Thyroid
      immunity tests demonstrated the presence of anti-peroxidase antibodies confirming
      the diagnosis of Hashimoto's thyroiditis. Chest x-ray and CT-scan are indicated
      in patients with autoimmune thyroiditis to search for a thymic mass. Conversely,
      search for autoimmune thyroiditis is warranted in patients with an identified
      thymic mass.

PMID- 14699300
TI  - [Acute infiltrative pneumonia].

PMID- 14699302
TI  - [Limitation and cessation of active treatment in resuscitation for adults.
      Recommendations of the French Language Resuscitation Society (SRLF)].

PMID- 14699303
TI  - [Shoulder arthroplasty for osteoarthritis after prior surgery for anterior
      instability: a report of 27 cases].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to analyze the natural
      history of shoulder osteoarthritis secondary to prior surgery for anterior
      instability, to evaluate clinical and radiological results of shoulder
      prosthesis, and to compare results with reports in the literature. MATERIAL AND
      METHODS: Twenty-seven shoulder prostheses (Aequalis) were implanted in patients
      with osteoarthritis of the shoulder after prior instability surgery. These
      shoulders were reviewed retrospectively at a mean follow-up of 46 months (range
      24-48). Prior surgery had been performed with coracoid block in two-thirds of the
      shoulders and with soft-tissue procedures in one-third. Twenty-four shoulders had
      had one instability procedure, several procedures had been performed in three.
      The Constant score was used to assess clinical status preoperatively and at last
      follow-up. Male gender predominated (16/27), and mean age at first dislocation
      was 31.6 years (4 patients experienced their first dislocation after the age of
      60 years). The patients had a mean 18.2 dislocations. The natural history of
      osteoarthritis was long: 24.2 years on the average. Mean age at arthroplasty was
      55.8 years. The preoperative images demonstrated an iatrogenic factor in 5
      shoulders and constructive osteoarthitis in 24. Posterior glenoid wear was
      observed in 24% of the cases, fatty degeneration of the subscapularis in 45% and
      full-thickness tears of the supraspinatus in 4 cases. The anterior scar tissue
      was released and implants were positioned anatomically in 26 cases. Total
      arthroplasty was used for 21 shoulders and a humeral prosthesis for 6. RESULTS:
      There were five complications including three anterior prosthetic instability,
      all three in patients who were over 60 years of age at their first instability
      surgery (one of these three patients required revision arthroplasty). Outcome was
      good or excellent in 56% of the shoulder with a mean weighted Constant score of
      83%: mean gain in pain score=8.3 points, in anterior elevation=51 degrees, in
      external rotation=33.5 degrees. The type of prior instability surgery and
      preoperative active external rotation had no determining effect on outcome.
      Factors correlated significantly with outcome were fatty degeneration of the
      rotator cuff muscles, particularly the subscapularis. DISCUSSION: Osteoarthritis
      of the shoulder has a long natural history, 26 years in our patients excepting
      those whose first dislocation occurred after the age of 60 years. Posterior
      glenoid wear, described by others, was only found in 24% of the shoulders in this
      series. Surgical dissection and release of anterior scar tissue was difficult.
      The overall results of arthroplasty were good and were correlated with fatty
      degeneration of the rotator cuff muscles, particularly the subscapularis, but not
      with the type of instability surgery. These results were less satisfactory than
      reported in series of arthroplasty for primary centred osteoarthritis:
      complications occurred in 18% of the shoulders with three cases of anterior
      dislocation. Unlike reports of arthroplasty after instability surgery where many
      of the patients had several operations, overall results in our series were not
      compromised by a large number of multiple interventions.

PMID- 14699304
TI  - [Effect of alendronate on periprosthetic bone loss after cemented primary total
      hip arthroplasty: a prospective randomized study].
AB  - PURPOSE OF THE STUDY: Bone remodeling and osteolysis around total hip prostheses,
      with its inevitable corollary, prosthesis loosening, remains a difficult problem
      in orthopedic surgery. Alendronate (bisphosphonate) has proven its efficacy for
      the treatment of osteoporosis of the lumbar spine and femoral neck. A few in
      vitro studies have pointed out its inhibiting effect on particle-induced
      osteolysis. In vivo, one study has demonstrated its usefulness in preventing
      osteolysis around non-cemented total hip arthroplasties (THA). The purpose of
      this work was to study the efficacy of this agent for the prevention of changes
      in peri-prosthetic bone mineral density (BMD) after primary THA. MATERIAL AND
      METHODS: The study series included 38 patients with degenerative hip disease who
      underwent THA. The patients were randomized in double-blind fashion to two
      treatment arms: 10 alendronate and 600 mg calcium per day for 2 years (20
      patients) or placebo and 600 mg calcium per day for 2 years (18 patients).
      Conventional x-rays and x-ray biphotonic absorptiometry (DPX) was performed on
      day four postop and at 3, 6, 12, and 24 months postop. The periprosthetic zones
      described by Gruen were used for analysis. RESULTS: DPX demonstrated a
      significant reduction in BMD in all patients included in the study. The bone loss
      was the same in both groups during the early postoperative period reaching
      maximum loss at 3 months. Differences were observed after this time. In the
      placebo group, bone loss reached a plateau at 6 months then BMD started to
      increase progressively, reaching 12.7% bone loss at 2 years follow-up (p<0.002).
      In the alendronate group, there was no plateau, BMD increased continuously
      starting from three months and reached 6.857% bone loss at 2 years (p<0.003).
      DISCUSSION: Administration of alendronate led to a significant reduction in peri
      prosthetic bone loss at 2 years follow-up. These results are the first to our
      knowledge demonstrating the beneficial effect in vivo of alendronate on bone
      behavior around cemented THAs. CONCLUSION: This beneficial effect observed in
      vivo should be confirmed in further studies including a larger number of patients
      and longer follow-up. The action of alendronate could facilitate and even retard
      revision surgery by preserving bone stock.

PMID- 14699305
TI  - [Femoral shaft fracture in children: treatment with early spica cast].
AB  - PURPOSE OF THE STUDY: Fractures of the femoral shaft are frequent in children and
      prognosis is good. For children aged less than 7 years, most authors propose
      orthopedic treatment using prolonged traction then cast immobilization, or
      orthopedic reduction under general anesthesia and early cast immobilization. The
      purpose of the present work was to analyze results of orthopedic treatment using
      a spica early for children aged less than 7 years in comparison with other
      published series with similar age or management. MATERIAL AND METHOD: Forty-seven
      unselected children aged less than 7 years with a closed fracture of the femoral
      shaft were treated by orthopedic reduction under general anesthesia and
      immobilization with a spica cast after a short period (<48 hr) of traction in the
      plane of the bed. Hip immobilization was set in flexion and minimal abduction,
      knee in flexion. The children were discharged the day the cast was installed or
      the next day. Follow-up examinations (tolerance) with x-rays cast in place were
      scheduled for day 8 and day 15. Clinical and radiological assessment was also
      recorded at removal of the cast, at 3 months, at 1 year, and at maximum follow
      up. RESULTS: Mean age was 37 months (range 2-83 months). Boys predominated (n=34,
      73%). Mean duration of traction was 1.13 days (range 0-5 days). Mean duration of
      cast immobilization was 45.4 days (range 28-78 days). Mean hospital stay was 2.8
      days (range 1-10 days). Four patients (8%) were rehospitalized for secondary
      displacement under the cast. Weight bearing was effective at day 49 (range 33
      78). Mean follow-up was 12.1 months (range 3 months-6 years). Five children
      (10.5%) developed leg length discrepancy greater than 10 mm. The anatomic axis of
      the femur in the saggital and frontal planes exhibited deviation in 7 children
      measuring less than 8 degrees in all cases. DISCUSSION: The localization and type
      of fracture observed in this series of children was similar to that reported in
      epidemiological studies. There were no treatment-related complications. In
      respect to healing time, deviation, and residual leg length discrepancy, results
      in this series were equivalent to those reported by others, irrespective of the
      treatment method employed. The major advantage of early spica is a short hospital
      stay allowing cost containment and rapid return to the child's everyday
      environment.

PMID- 14699306
TI  - [Study of the patellar apex in objective patellar dislocation].
AB  - PURPOSE OF THE STUDY: The purpose of this work was to study the morphology of the
      patella in search of dysplasia typical of objective patellar dislocation.
      MATERIAL AND METHODS: One hundred forty patients (190 knees), 80 women and 60
      men, who underwent surgery between 1988 and 1999 were included in this study.
      Mean age was 22.6 years (range 13-47). Patellar morphology was analyzed on the
      preoperative lateral x-rays (n=190) taken at 30 degrees flexion. The apex of the
      patella was measured as well as the length of the patellar tendon. The width of
      the patella was measured on the computed tomography scan (n=158). For 64 knees,
      magnetic resonance images of the patella were available on which the length and
      width of the patella, the articular surface, and the patellar tendon were
      measured. Ninety contralateral knees were symptom free and x-rays were available
      for 67. RESULTS: According to the Grelsamer classification, 80% of the patellae
      presented a normal apex. The length of the patellar apex was significantly
      shorter when the patellar ligament was longer. Using the Wiberg classification,
      men had more dysplasic patellae (grade C) (p=0.007). There was also a correlation
      between the Wiberg classification and the Maldague classification. The length of
      the medial border of the patella and the patellar angle were 2 factors directly
      related to the Wiberg classification. Mean width of the patella was 39.1 mm
      (computed tomography measurements). The mean length of the patellar tendon was
      53.8 on the magnetic resonance images with a mean articular surface measuring
      30.8 mm, a mean patellar length measuring 40.6 mm, and a mean width measuring
      38.7 mm. There was no correlation between trochlear dysplasia and patellar
      morphology. DISCUSSION: There is little data in the literature concerning
      patellar morphology since Wiberg's work in 1941. The hypothesis of patellar
      dysplasia rather than trochlear dyplasia, the principal factor involved in
      objective patellar dislocation, has not been explored extensively. The presence
      of a hypoplasic medial border, Wiberg grade C, or a short patellar apex suggests
      that a particular patellar morphotype would be involved in objective patellar
      dislocation.

PMID- 14699307
TI  - [Patellar reconstruction during total knee arthroplasty after previous
      patellectomy].
AB  - PURPOSE OF THE STUDY: In order to limit the consequences of prior total
      patellectomy on knee function after total knee arthroplasty, we propose an
      original technique using an en bloc patellar graft to reconstruct the quadriceps
      lever arm. The purpose of this work was to describe the technique and present
      preliminary results obtained in seven patients. PATIENTS AND METHODS: Seven en
      bloc patellar grafts were performed in seven patients (6 women and 1 man) during
      total knee arthroplasty procedures for femorotibial degenerative joint disease
      after prior patellectectomy (mean 13 years before arthroplasty, range 5-20
      years). We implanted three posterior stabilized prostheses, one ultracongruent
      prosthesis, two prostheses preserving the posterior cruciate ligament, and one bi
      cruciate prosthesis. The patella was reconstructed with an autologous bone graft
      fashioned from the tibial plateau in six cases, and with a homologous graft
      fashioned from a bone-bank femoral head in one. Transosseous sutures were used to
      fix the graft to the extensor system. A polyethylene button was cemented on five
      of the grafts. RESULTS: Active extension was defective in five knees prior to the
      patellar graft and in only one knee after patellar reconstruction. The IKS knee
      score improved from 41 points (range 35-45) before surgery to 78 points (range 55
      95) after grafting and the IKS function score from 35 (range 5-50) to 72 (range
      40-100). Four of the seven grafts were removed (eight weeks to five years after
      implantation, mean two years) mainly due to failure of fixation leading to
      progressive migration. Follow-up varied from eight weeks to six years. Mean
      follow-up for the three grafts still in place was 4.6 years (4-6 years). After
      removing the patellar graft (4 knees) the IKS knee score decreased to 68 points
      (20-95) and the IKS function score to 62 points (30-100). Lack of active
      extension reappeared in three of the knees after removing the patellar graft but
      was not observed in the three knees with the patellar graft in place (and flexion
      was at least 110 degrees ). Microradiography of the patellar graft explanted
      after two years revealed peripheral corticalization with areas of living bone
      tissue seen on the pathology specimens. Inversely, the autografts explanted at
      eight weeks and at five years exhibited bone necrosis. CONCLUSION: This
      preliminary study shows that patellar autograft can improve the performance of
      total knee arthroplasty on patellectomized knees. The fixation technique must be
      improved using transosseous transverse sutures in addition to peripheral sutures
      in order to limit secondary migration of the graft. A patellar autograft fixed
      into the extensor system can remain viable two years after implantation. This
      technique can be proposed when total knee arthroplasty is indicated for a
      patellectomized knee, particularly in patients with lack of active extension.

PMID- 14699308
TI  - [Long-term results of surgical treatment of lumbar spinal stenosis].
AB  - PURPOSE OF THE STUDY: Some discussion remains concerning the quality of the long
      term functional outcome after surgical treatment of lumbar spinal stenosis. The
      purpose of this retrospective observational study was to evaluate outcome ten
      years after surgical treatment of lumbar spinal stenosis and to determine the
      rate of reoperation as well as to identify factors influencing outcome at last
      follow-up. MATERIAL AND METHODS: Between January 1990 and December 1992, 141
      patients underwent surgery for lumbar stenosis all were included in present
      study. Mean follow-up was ten years. At last follow-up, functional signs were
      assessed with a designated self-administered questionnaire with items for lumbar
      and radicular pain, signs of radicular ischemia, and patient satisfaction and two
      visual analog scales for lumbar and radicular pain. Other data recorded included:
      epidemiological and morphological features of the study population,
      comorbidities, presence or not of objective neurological signs, anatomy of the
      stenosis, and results of two self-administered questionnaires on quality of life
      (SF36) and anxiety-depression (GHA28). Two data analysis methods were applied.
      The first was a descriptive analysis to quantify the importance of functional
      signs observed at last follow-up, patient satisfaction, and rate of recurrence as
      well as reasons for reoperation. The second was a multivariate analysis designed
      to identify factors influencing the score obtained on the designated stenosis
      self-administered questionnaire. RESULTS: Fifteen patients had undergone a
      revision procedure on the lumbar spine. At last follow-up overall satisfaction
      was 71%. The best results were obtained for radiculalgia and intermittent
      neurogenic claudication. Residual lumbalgia was the main complaint at last follow
      up. The patient's psychological profile was found to be the predominant factor
      influencing functional outcome. Other factors having an effect in this population
      were: reoperation, persistence of objective neurological disorders, degree of
      comorbidity. CONCLUSION: For the majority of patients, surgical treatment of
      lumbar spinal stenosis provides good long-term results and patient satisfaction.
      At ten years, the risk of reoperation was 10% in this population. Compared with
      data in the literature, these results are better than with medical treatment.
      Surgery enables these patients to have a quality of life similar to an age
      matched control population.

PMID- 14699309
TI  - [Geometrical and mechanical analysis of lumbar lordosis in an asymptomatic
      population: proposed classification].
AB  - PURPOSE OF THE STUDY: The main objective of this study was to describe the
      morphology and the mechanism underlying the organization of lumbar lordosis in
      terms of position and shape of the pelvis. A classification of lumbar lordosis
      was proposed based on the orientation of the sacral plane. MATERIAL AND METHODS:
      One hundred sixty asymptomatic young adult volunteers were x-rayed in a
      standardized standing position. A dedicated software was used for analysis of the
      spine and pelvis. The pelvic parameters were: pelvic incidence, sacral slope,
      pelvic tilt. The point separating thoracic kyphosis and lumbar lordosis was
      called the inflexion point. Lumbar lordosis was bounded by the sacral plate and
      the inflexion point. At the apex, the lumbar curve was divided into two tangent
      arcs of circle, quantified by an angle and the number of included vertebrae. The
      lower arc was geometrically equal to the sacral slope. Regarding the vertical
      line, a lordosis tilt angle was drawn between the inflexion point and the frontal
      limit of the sacral plate. RESULTS: The value of the lumbar lordosis was very
      variable. The best correlation was between lumbar lordosis and sacral slope, then
      between sacral slope and pelvic incidence. The upper arc of a circle remained
      constant while the lower arc changed with sacral slope. Good correlations were
      found between the sacral slope and the position of the apex and between sacral
      slope and lordosis tilt angle. DISCUSSION AND CONCLUSION: Regarding sacral slope,
      lumbar lordosis can be classified into four types. When the sacral slope is low,
      lumbar lordosis can either be both short and curved with a low apex and a
      backward tilt (type 1) or both long and flat with a higher position of the apex
      (type 2). When the sacral slope increases, lumbar lordosis increases in angle and
      number of vertebrae with an upper apex, with a progressively forward tilt (types
      3 and 4). Depending on the shape and position of the pelvis, and because of the
      relation between sacral slope and pelvic tilt, the morphology of lumbar lordosis
      could be the main mechanical cause of degenerative diseases of the lumbar spine.

PMID- 14699310
TI  - [Gluteus medius tendon tear and degenerative hip disease].
AB  - We report three cases of gluteus medius tendon tears discovered fortuitously in
      patients undergoing total hip arthroplasty. The tears were not suspected from the
      initial clinical presentation. Sutures were possible in only one patient. Outcome
      of the hip arthroplasty was very good in all three patients despite lack of
      tendon repair in two.

PMID- 14699311
TI  - [Surgical treatment of a femoral agenesis: a case report].
AB  - We report a case of severe femoral agenesia in an adult and propose a new
      surgical approach facilitating prosthesis fitting. The procedure involves
      insertion of a total hip arthroplasty, arthrodesis of the knee and amputation of
      the foot. The final prosthesis fits on the crural area with weight bearing on the
      ischiatic region, the lesser pelvis, and the articulated knee. Outcome was
      satisfactory at one year in our patient. Other surgical alternatives are
      presented.

PMID- 14699312
TI  - [Talo-crural migration of a Kuntscher tibial nail: a case report].
AB  - Centromedullary nailing without locking using a Kuntscher nail remains a routine
      practice in developing countries for the treatment of leg fractures. We observed
      a distal transplantar migration of this type of nail which had not been removed
      and report here the etiopathogenic factors involved as well as the clinical
      evolution. In our patient, transplantar migration was favored by mechanical
      phenomena related to microtrauma caused by the tip of the nail which eroded bony
      structures of a limb highly solicited for nearly 16 years.

PMID- 14699313
TI  - [Guidelines for clinical practice: Ectopic pregnancy management].

PMID- 14699315
TI  - [Epidemiology of ectopic pregnancy: incidence, risk factors and outcomes].
AB  - Two entities must be differentiated in ectopic pregnancy (EP) epidemiology: EP
      occurring in women without contraception (reproductive failure) and with
      contraception (contraceptive failure). These two entities differ on almost all
      issues. After a great increase between 1970 and 1990, incidence of EP has
      decreased over the next 10 years. At the present time, the incidence of EP with
      contraception goes on decreasing while the incidence of EP without contraception
      is increasing. Three quarters of EP are ampullary, and 4.5% are extra-tubal. The
      two main risk factors for EP without contraception are a history of infection or
      tubal surgery and smoking. Quantitatively, their relationships with EP risk are
      similar. The other risk factors are age, prior spontaneous abortion, prior
      induced abortion, previous use of an intra-uterine device, and history of
      infertility. The total attributable risk of all these factor is 76%. Maternal
      mortality following EP is quite uncommon in developed countries. Immediate
      morbidity is not sufficiently documented, however long-term psychological
      consequences may be important.

PMID- 14699316
TI  - [Ectopic pregnancy: interest and value of clinical examination in management
      policy].
AB  - Clinical examination (history and physical examination) is not considered to be a
      useful tool in the diagnosis of ectopic pregnancy (EP). In this systematic review
      we aimed to evaluate its value when ancillary tests are not readily available or
      when they are equivocal. Suspicion of EP is based on the presence of one or more
      of the following signs: vaginal bleeding, acute pelvic pain, or any risk factors
      for EP occurring in a pregnant woman. Detection of early pregnancy by urinary or
      serum hCG testing must be systematic because neither medical history nor physical
      examination can rule out early pregnancy with a high level of confidence. No
      isolated sign has sufficient diagnostic accuracy to rule out EP. In presence of
      vaginal bleeding without pain and if abdominal and pelvic examination are normal
      the risk of EP is very low. The presence of spontaneous pain moderate to severe,
      peritoneal signs, or definite pain during digital cervical mobilization increase
      the probability of EP. Absence of these signs does not rule out EP but tend to
      eliminate tubal rupture. In the presence of these signs one may consider an
      emergency transfer in a specialized center. In their absence, suspicion of EP may
      have outpatient diagnosis procedures.

PMID- 14699317
TI  - [Contribution of ultrasonography in the diagnosis of ectopic pregnancy].
AB  - High-resolution endovaginal sonography has considerably improved ectopic
      pregnancy imaging. In conjunction with serum hCG measurements, it allows early
      detection of ectopic pregnancy (EP) and has significantly reduced the morbidity
      and the mortality of this disease. The major sonographic finding is the uterine
      vacuity, the diagnosis of ectopic pregnancy is quite sure in case of absence of
      intra-uterine pregnancy (IUP) associated with serum hCG above 1500 mUi/ml.
      Conversely, the presence of IUP excludes practically the diagnosis of EP, but IUP
      must be distinguished from a pseudosac. The visualization of an ectopic sac that
      contains an embryo or a yolk sac clearly allows the diagnosis of EP, but its
      sensitivity is only 25%. The most common sonographic finding is a hematosalpinx,
      which looks like an echogenic adnexal mass, next to the ovary containing the
      corpus luteum. Color Doppler is useful to enhance ectopic trophoblastic flow, but
      it is only a complementary technique of endovaginal sonography. Finally, if the
      first sonography is inconclusive, a follow-up examination must be performed 2 or
      4 days later.

PMID- 14699318
TI  - [Ectopic pregnancy: contribution of paraclinical investigations, ultrasonography
      excluded].
AB  - Because a misdiagnosis of ectopic pregnancy (EP) exposes patients to a vital
      risk, paraclinical exams have to be highly specific and as sensitive as possible.
      As the accuracy of diagnostic tools depends on the prevalence of the disease in
      different patient groups, clinical signs have to be considered when analyzing the
      literature (symptom-free women, complaints, risk factors...). In the first part
      of this review, various diagnostic tools are reviewed and the particular features
      of EP after assisted reproduction techniques are taken into account. The
      evaluation of serum quantitative betahCG level is primordial. In difficult cases
      when transvaginal ultrasound does not detect an intrauterine gestational sac,
      repeated betahCG measurements and determination of serum progesterone levels
      allow to evaluate the viability of an early pregnancy. If ultrasound diagnosis
      cannot be obtained without significant delay, culdocentesis is easy to perform
      and has a good positive predictive value. However, the detection of intrauterine
      chorionic villi is only of limited diagnostic value, whereas hysteroscopy may be
      of interest in some cases. In the second part an analysis of algorithms in the
      diagnostic management of EP is carried out. Currently, a standard protocol should
      not be applied for all patients and specific algorithms have to be defined
      according to the prevalence of EP in the treated population.

PMID- 14699319
TI  - [Ectopic pregnancy: criteria to decide between medical and conservative surgical
      treatment?].
AB  - OBJECTIVE: To search for criteria which should be used to decide between medical
      treatment and conservative laparoscopic treatment of ectopic pregnancy. METHOD: A
      Medline search was conducted via Pubmed and in the Cochrane Library. Other
      studies were selected from the references used in recent randomized trials.
      RESULTS: Results of medical and of conservative laparoscopic treatment have been
      similar in patients selected for prospective randomized trials. The criteria used
      to include patients in these studies were determined arbitrarily. Two scores were
      evaluated prospectively, they included criteria which may be difficult to use in
      clinical practice. CONCLUSION: The treatment should performed surgically if the
      patient is hemodynamically unstable, ss-hCG is >10,000 mUI/mL, the ectopic
      pregnancy is > or =4 cm in diameter, if there is a medical contraindication to
      methotrexate, and if the patient may not be followed adequately after treatment.
      Medical treatment should be preferred if the patient has undergone surgery many
      times previously, has extensive pelvic adhesion, a contraindication for general
      anesthesia, a cornual pregnancy, and after failure of a conservative laparoscopic
      treatment. Medical treatment is possible: if ss-hCG is below 5,000 or 10,000
      mUI/mL, if the ectopic pregnancy is less than 4 cm in diameter or if the score is
      adequate when a scoring system prospectively evaluated can be used. Medical
      treatment should be preferred: if ss-hCG<1000 mUI/mL, if the patient has no pain
      and if the ectopic pregnancy cannot be visualized at ultrasound.

PMID- 14699320
TI  - [Management of non-surgical treatment of ectopic pregnancy].
AB  - OBJECTIVE: To define non-surgical management of ectopic pregnancy using expectant
      management or medical treatment. METHODS: We reviewed French and English reports
      on Pubmed using to the following key words: "ectopic pregnancy, medical
      treatment, methotrexate, expectant management". RESULTS: Expectant management is
      possible for patients if they are selected according to precise criteria. It
      avoids therapeutic escalation, if there is a doubt as to whether it is a
      miscarriage or an ectopic pregnancy or for asymptomatic patients with spontaneous
      decreased hCG levels. Methotrexate is the medical treatment of choice. Side
      effects appear more rarely after one injection than multiple injections.
      Therefore, after multiple injections, it seems to be good to associate folinic
      acid. Local administration under sonographic control and mifepritone seem to be
      more efficient than intramuscular injection in case of active ectopic pregnancy
      (progesterone level and hCG level high). Two treatment protocols, the single dose
      and the multidose, have been reported and results are comparable when the success
      rate is defined as a negative hCG level associated with non-surgical
      intervention. This management can be handled on an outpatient basis but the
      patient's acceptance must be complete. Decreased hCG level is controlled in
      comparison with a standard curve. An additional dose of methotrexate is necessary
      when hCG levels are above the value of the curve on day 2, day 4, day 7 or day
      10. Surgical management is necessary in case of tubal rupture. The occurrence of
      pain following methotrexate therapy should not be the sole indication for
      surgical intervention.

PMID- 14699321
TI  - [Surgical treatment of ectopic pregnancy].
AB  - Recent advances in therapeutics have considerably modified the management of
      ectopic pregnancy. However, surgical management is still indicated in some
      patients. Laparoscopic procedure is the reference surgical approach for the
      management of ectopic pregnancy. It reduces length of hospital stay, analgesic
      requirement, hospital cost, the risk of post-surgical adherence and is also
      associated with lower morbidity and better esthetic appearance. Laparotomy is now
      only performed in individuals for whom laparoscopy is contra-indicated. Patients
      can be treated conservatively, tubotomy with removal of the products of
      conception or radically, salpingectomy. In order to lower the failure rate and
      the risk of re-occurrence, some operative procedures are required including
      regular washing of the abdominal cavity, adhesiolysis and extraction in a
      protective bag. The choice of treatment is generally guided by the patient's past
      medical history and the wish to bear future children.

PMID- 14699322
TI  - [Fertility after ectopic pregnancy and indications of ART].
AB  - There is no simple answer to the problem of fertility after one ectopic
      pregnancy. Results reported in the literature have been satisfactory with rate of
      subsequent pregnancy about 60% and the risk of new ectopic pregnancy (EP) around
      28%. We have deliberately excluded studies before 1990 except when the
      methodology was particularly good or the treatment particularly interesting.
      Strict and exhaustive criteria were lacking in most of these studies due to
      widely varying aims, the prospective or retrospective nature of the data, the
      number of patients included, and varying therapeutic decision-making schemes.
      Many patients were lost to and no mention is given concerning the proportion of
      patients who desired a subsequent pregnancy. Infertility factors were not
      considered in most cases. We were looking for fertility results according to
      treatment used. Among the 50 studies we retained, pregnancy rates after ectopic
      pregnancy were satisfactory whatever treatment was used, with laparoscopy being
      the gold standard. Medical treatment was at least as effective as surgical
      treatment. Associated infertility factors appeared to be the most important for
      fertility outcome. It is unfortunate that so few study have analyzed outcome in
      these patients without considering risks factors of EP, infertility factors and
      the proportion of women who attempted to conceive again.

PMID- 14699323
TI  - [Management of other ectopic pregnancies (cornual, interstitial, angular,
      ovarian)].
AB  - OBJECTIVES: To provide recommendations for management of interstitial and ovarian
      pregnancies. MATERIALS AND METHODS: A Medline search was conducted and discussed
      by a study group of experts. RESULTS: Ovarian and interstitial pregnancies are
      rare forms of ectopic pregnancy. Diagnostic criteria and methods are described on
      the basis of a review of the literature. Surgery is the usual management of
      interstitial pregnancy. Conservative treatment has replaced hysterectomy.
      Laparoscopy is an attractive way to manage interstitial pregnancies but
      laparotomy may still be used. Cornual resection is required. Medical treatment
      with methotrexate is another alternative. Local MTX seems to be more efficient
      than systemic administration. Management of interstitial pregnancy under
      laparoscopic control is an attractive way if feasible. Strong recommendations
      cannot be established due to the small number of reported cases reports. The pre
      therapeutic score cannot be used as doses are still not clear for interstitial
      pregnancies. For ovarian pregnancy, management is often surgical. Laparoscopy is
      more and more used for small gestational sacs. Methotrexate has also been used
      for ovarian pregnancies. Laparoscopic treatment associated with systemic MTX
      seems to be the more efficient way. CONCLUSION: Because of limited data it is
      very hard to establish recommendations from low power studies (NP 5).

PMID- 14699324
TI  - [Ectopic pregnancy management: cervical and abdominal pregnancies].
AB  - Cervical or abdominal pregnancies are rare forms of ectopic pregnancy and their
      management differs for different authors. Besides, the literature is mainly made
      of case-reports. The aim is to propose one or more management possibilities,
      keeping in mind that the level of proof obtained from the references used is
      insufficient to be affirmative. For cervical pregnancy, although hysterectomy is
      the reference treatment (especially in advanced pregnancy or hemorrhagic life
      threatening forms), technical improvements in ultrasonography make feasible the
      diagnosis of non or weakly symptomatic forms, which could be treated
      conservatively in order to preserve fertility of these women. In this diagnostic
      situation the present treatment standard is methotrexate combined with intra
      amniotic feticide in case of viable cervical pregnancy. Diagnosis of abdominal
      pregnancy is often made late. Treatment consists in laparotomy which enables
      better vascular control. Placental ablation remains as often as not dangerous and
      in most cases, it is better to abandon the attempt.

PMID- 14699325
TI  - [Ectopic pregnancy management. Guidelines].

PMID- 14699327
TI  - [Conclusions of the National Childbirth Conference (Paris, June 6, 2003)].

PMID- 14699328
TI  - [Delivery and birth in France: proposition for changing childbirth. Communication
      from the National Childbirth Conference (Paris, June 6, 2003)].

PMID- 14699329
TI  - [Action for improving perinatal health: insight from the AUDIPOG sentinel
      network].

PMID- 14699330
TI  - [Home delivery: myth or model?].

PMID- 14699331
TI  - [Gynecologic laparoscopy and abdominal scars: what approach for the peritoneal
      cavity?].
AB  - To identify and discuss the advantages of the different methods of entry into the
      peritoneal cavity during gynecological laparascopy in patients who have
      previously undergone abdominal surgical procedures. Literature review comparing
      the strengths of each method of entering the peritoneal cavity during
      gynecological laparoscopic procedures. Adhesions increase the risks of access
      into peritoneal cavity during laparoscopy. Many techniques or safety rules have
      recently been described or re-evaluated as an alternative to using the
      traditional combination "Veress needle and blind introduction of the first
      trocar". The most relevant were the "open laparoscopy", the use of optical
      trocar, the double laparoscopy and the use of microlaparoscope. There remains no
      clear conclusion regarding the optimal form of laparoscopic entry in high risk
      patients. Relevant data emphasizes that critical to the surgeon's choice of
      technique is the immediate ability to recognize accidental injury and the
      capacity to avoid the scarred area. According to the literature review on the
      procedures used for entering the peritoneal cavity in high risk patients, we
      conclude that double laparoscopy may indeed be an underused procedure in such
      cases.

PMID- 14699332
TI  - [Verrucous carcinoma of the vulva: a tailored treatment].
AB  - OBJECTIVE: Verrucous carcinoma is a rare form of vulvar squamous carcinoma, with
      particular clinical presentation and histological description. We analyze the
      specificity of the treatment of this form. MATERIALS AND METHODS: We analyzed the
      records of 8 patients treated in our hospital between 1995 and 2001. In the
      absence of an associated lesion, the treatment was partial vulvectomy without
      lymph node dissection. A close follow-up was then organized. RESULTS: Mean age
      was 76 years (range 54 to 92). In 7 out of the 8 cases we found an associated
      lesion: invasive squamous carcinoma, VIN III or lichen. Two patients later
      developed a squamous carcinoma. Two others died because of intercurrent diseases.
      The last four patients are doing well. CONCLUSION: We confirm the efficacy of the
      treatment generally proposed: partial vulvectomy, without lymph node dissection
      and without complementary treatment but with a close follow-up. The coexistence
      of other vulvar lesions such as lichen is remarkable in our series.

PMID- 14699333
TI  - [Survey of the practice of cervical ripening and labor induction in France].
AB  - OBJECTIVES: Labor induction is a widespread medical practice in France. The
      medical or obstetric indications for induction as well as the protocols used
      probably vary from one maternity to another. The objective of this national
      survey was to describe current medical practices and procedures in France,
      regarding labor induction and cervical ripening, eight years after the national
      consensus on labor induction management. A second objective was to assess
      mothers' opinion on the induction of their labor/level of satisfaction on their
      childbirth experience. MATERIALS AND METHODS: The sample of maternities was
      randomly extracted from a list published by the French Ministry of Health.
      Sampling was performed according to maternity size, geography, and private vs
      public. Medical information was collected on consecutive labor induction cases in
      each maternity. Mother's opinions were estimated through a score based on the
      validated Labour Agentry Scale. RESULTS: Within the 38 maternities included, 21
      (55.3%) were public, and 17 (44.7%) private. 1192 women were included in this
      study and 1090 (91.4%) answered the questionnaire on level of satisfaction.
      Global rate of elective induction (no medical or obstetric indication) was 24.8%
      (n=295). Prostaglandins are almost as widely used as oxytocin (45.8% and 47.7% of
      total labor inductions, respectively). Mostly used methods of delivering
      prostaglandin are intravaginal (27.1%), controlled-release pessaries (10.2%) and
      intracervical (8.1%). Among the elective inductions, an important rate of
      unfavorable cervix was found (n=81, 27.5%) as well as a quite high level of use
      of prostaglandins (n=51, 17.3%). The statistically independent criteria linked to
      a high satisfaction score are an older age (OR=1.58; CI 95% [1.80-3.33]), an
      elective induction (OR=2.44; IC 95% [1.80-3.33]) and a favorable cervix (OR=1.47;
      [1.08-1.98]). CONCLUSION: The use of prostaglandins in labor induction and
      cervical ripening is now widespread in France. This technique is not always used
      in accordance with available scientific data. These results should lead health
      professionals to set up an evaluation process for their practices, when these are
      not based on clear scientific evidence.

PMID- 14699334
TI  - [Anemia prevalence in pregnant and breast-feeding women in Lubumbashi (Democratic
      Republic of the Congo). Impact of malaria and intestinal helminthiasis].
AB  - OBJECTIVE: To determine the prevalence of anemia and associated factors (malaria
      and intestinal helminthiasis) in high risk groups of Lubumbashi, Congo,
      particularly in pregnant and breast-feeding women and children aged 1-2 years.
      MATERIAL AND METHODS: From March to May 2002, 632 pregnant women, 570 breast
      feeding women, and 570 infants (1-2 years) were examined in three medical centers
      in Lubumbashi, Congo. Some of the subjects lived in deprived semi-urban areas
      (Bongonga and Sendwe), others in urban areas with a satisfactory socio-economic
      situation (University Clinic). RESULTS: Overall frequency of anemia was estimated
      between 50 and 80% in the study populations. The proportion of anemic cases was
      clearly higher in the Sendwe and Bongonga populations (70-80%) than in the other
      urban populations (50%) (P<0.01). For the three categories of examined subjects,
      anemia was found to be most prevalent among pregnant women (P<0.05). Anemia was
      found to be associated with malaria in 40% of the patients and with intestinal
      parasitism (ascaris / ankylostoma) in 9%. CONCLUSION: Considering these results,
      systematic screening and treatment of anemia and associated factors such as
      malaria and intestinal helminthiasis is needed for the Lubumbashi population.

PMID- 14699335
TI  - [Myasthenia gravis and pregnancy. Report on 13 cases].
AB  - OBJECTIVES: To evaluate our experience of myasthenia during pregnancy. MATERIALS
      AND METHODS: Retrospective study in a tertiary care university hospital including
      pregnant women affected by myasthenia gravis and who delivered in the obstetrical
      tertiary center. Medical and delivery reports were analyzed. RESULTS: Between
      1994 and 2002, 12 women, age 31 (25-36), delivered 14 children. One women
      delivered twice, and there was one twin pregnancy. Clinical symptoms of
      myasthenia worsened in five. One was admitted twice to the intensive care unit
      during her pregnancy. Two were admitted to intensive care unit during the first
      month of post-partum. Gestational age at birth was 39.3 weeks (38-40.6), all
      birth weights were normal: 3329 g (2660-4520). Six women delivered vaginally, two
      by instrumental extraction and five by cesarean section. Apgar score was normal
      for all infants: 9/10. The level of anti-acetylcholine receptor antibodies (anti
      AchR) was high: 36.4 nM/L (0-46.8) (normal below 0.6 nM/L), but was not related
      to neonatal outcome. Three children presented neonatal myasthenia. CONCLUSION: We
      recommend obstetrical monitoring in tertiary centers for pregnant women with
      myasthenia gravis because of the risk of neonatal myasthenia. Measurement of anti
      acetylcholine receptor antibodies may be useful. Pediatric and maternal
      observation is necessary in the first days of post partum.

PMID- 14699336
TI  - [Severe neonatal myasthenia with arthrogryposis].
AB  - Maternal myasthenia gravis has been associated with the presence of neonatal
      myasthania and sometimes fetal congenital anomalies. The purpose of this paper is
      to present an infant with multiple deformations born to a mother with myasthenia
      gravis. The infant presented with arthrogryposis multiplex and pulmonary
      hypoplasia. The new born died within the first day of life. Twenty-seven other
      cases of neonatal myasthenia with arthrogryposis have been reported. Twenty-two
      of them were stillborn or died. The surviving children needed ventilatory
      assistance for a long period.

PMID- 14699337
TI  - [Peritoneal gliomatosis. A case report and review of the literature].
AB  - OBJECTIVE: We report the case of a 14-year-old patient referred for right mature
      ovarian teratoma; recurrent gliomatosis peritonei developed. MATERIAL AND
      METHODS: The diagnosis of peritoneal recurrence was suspected due to pelvic pain
      and abnormal findings at ultrasound. Two operations were performed, 18 and 30
      months after the initial treatment, to resect peritoneal implants. Histological
      examination revealed mature and benign gliomatosis peritonei. RESULTS: Eighty-six
      cases have been published in the literature. Although potential for recurrence is
      high, the risk of malignancy is very low. CONCLUSION: Gliomatosis peritonei is a
      rare situation, characterized by the recurrence of peritoneal implants after the
      surgical treatment of ovarian teratoma. This entity does not modify the good
      prognosis of mature teratomas, but we recommend regular follow-up.

PMID- 14699341
TI  - Innovations from hell's fury.

PMID- 14699342
TI  - Patching things up: humorizing your schnoz.

PMID- 14699344
TI  - Caring for our own.

PMID- 14699346
TI  - Build your own bariatric unit: Southwest Ambulance creates a better way to
      transport obese patients.

PMID- 14699347
TI  - Autonomic dysreflexia: one more way EMS can positively affect patient survival.
AB  - Autonomic dysreflexia is a life-threatening medical condition that affects people
      with spinal cord injuries above T6. Caused by the division of the autonomic
      nervous system, it can result in disastrous hypertension. Although complicated in
      nature, AD can be quickly treated and reversed by prehospital providers. The
      prompt emptying of a patient's bladder and/or bowels will resolve most
      occurrences. Other factors that can't be resolved in the prehospital setting may
      cause AD. In these situations, quickly transport the patient to a definitive care
      facility and consider the use of antihypertensive agents. Bladder catheterization
      and digital bowel emptying are not everyday EMS skills. They are, however, skills
      within the range of EMS abilities. Providers should contact their medical
      directors or training supervisors to obtain the training necessary to carry out
      both techniques. Having these skills will arm you with the necessary abilities to
      mitigate an episode of autonomic dysreflexia.

PMID- 14699348
TI  - Nasal drug delivery in EMS: reducing needlestick risk.

PMID- 14699349
TI  - 5-Step asthma approach: managing acute asthma in 5 steps or less.
AB  - Asthma requires immediate and expert care. Definitive therapy can begin in the
      field with most patients, who will significantly improve by the time they arrive
      at the ED. Paramedics become expert caregivers when they provide oxygen,
      administer combined continuous nebulization of beta agonists and
      anticholinergics, and consider magnesium and epinephrine for asthmatics with
      severe symptoms.

PMID- 14699350
TI  - Mechanical ventilation: understanding respiratory physiology & the basics of
      ventilator management.

PMID- 14699351
TI  - The unique patient identifier for EMS: it's simple, but it works.

PMID- 14699354
TI  - Jingle bells, the pager wails!

PMID- 14699355
TI  - EMS needs a few more cowboys.

PMID- 14699358
TI  - Pediculosis.
AB  - The 3 major lice that infest humans are Pediculus humanus capitis (head louse),
      Pthirus pubis (crab louse), and Pediculus humanus humanus (body louse). Patients
      with louse infestation present with scalp pruritus, excoriations, cervical
      lymphadenopathy, and conjunctivitis. A hypersensitivity rash, or pediculid, may
      mimic a viral exanthem. Head lice infestation crosses all economic and social
      boundaries, whereas body lice infestation preferentially affects the homeless and
      displaced. Body lice are major vectors of diseases such as typhus, trench fever,
      and relapsing fever. Pubic lice infestation often is acquired as a sexually
      transmitted disease and may be a marker to screen for other sexually transmitted
      diseases. Treatment of louse infestation can be challenging. Mechanical measures,
      such as combing, are helpful as adjunctive measures, but most studies suggest
      they are not as effective as chemical agents. Resistance to chemical agents is a
      growing problem. Major types of resistance include knock-down resistance,
      glutathione-S-transferase-based resistance, and monooxygenase-based resistance.
      Research is needed to identify new effective treatments.

PMID- 14699359
TI  - Detection of melanomas in patients followed up with total cutaneous examinations,
      total cutaneous photography, and dermoscopy.
AB  - BACKGROUND: Many factors have been identified as important determinants that
      increase the risk of malignant melanoma (MM) developing. Patients with classic
      atypical mole syndrome (CAMS) have multiple such factors and are known to be at
      high risk for MMs developing. OBJECTIVE: We sought to evaluate the risk for newly
      diagnosed MMs developing in patients with CAMS and in a heterogeneous group of
      patients at high risk (ie, those with high-risk non-CAMS [HRNCAMS]) who had 1 or
      more risk factors: personal history of nonmelanoma skin cancers; family history
      of melanoma; biopsy specimen-confirmed dysplastic nevi; and meeting 1 or 2 of the
      3 CAMS criteria. We also aimed to report our experience treating these patients
      at high risk with annual total cutaneous examination, total cutaneous
      photography, and dermoscopy. METHODS: Consecutive medical records from a private
      dermatology practice were reviewed. A total of 258 patients were selected who
      fulfilled the criteria of having: (1) total cutaneous photography as an aid for
      follow-up; (2) total cutaneous examination at least once per year; (3) at least 6
      months of clinical follow-up; and (4) no personal history of melanomas. A total
      of 160 patients with CAMS and 98 with HRNCAMS were included in this study. The 10
      year risk for MM developing in these 2 cohorts was computed using the Kaplan
      Meier method. RESULTS: In the CAMS cohort, 28 new MMs developed in 19 patients
      resulting in a cumulative 10-year risk of 14% (95% confidence interval: 7-20). In
      the HRNCAMS cohort, 10 new MMs developed in 9 patients, and the cumulative 10
      year risk was 10% (95% confidence interval: 2-17). The difference between the 2
      groups was not statistically significant (P=.91). The MMs diagnosed in both
      cohorts were either in situ or less than 1 mm in Breslow thickness. There were no
      MM metastases or MM-related deaths in either cohort during a mean follow-up
      period of 120 months for the CAMS and 98 months for the HRNCAMS group.
      CONCLUSION: Both the patients with CAMS and HRNCAMS were at very high risk for
      MMs developing. The combination of total cutaneous photography, total cutaneous
      examination, and dermoscopy were used in treating our patients. No MM 1 mm or
      greater in thickness developed during follow-up in either group.

PMID- 14699360
TI  - Advanced presentation of melanoma in African Americans.
AB  - BACKGROUND: Melanoma in African Americans is rare, and the diagnosis is often
      delayed, leading to advanced presentation and poor prognosis. OBJECTIVE: The
      purpose of this retrospective study is to determine whether African American
      patients diagnosed with melanoma at the Washington Hospital Center were initially
      seen with more advanced disease than white patients. METHODS: A retrospective
      chart review was performed on 36 African American patients who were diagnosed
      and/or treated for melanoma at the Washington Hospital Center between 1981 and
      2000. Data obtained included patient age at presentation, sex, Breslow's depth
      and histologic subtype, stage at presentation, and tumor location. These data
      were compared with information obtained from white patients with melanoma during
      this period. RESULTS: A total of 649 African American and white patients were
      treated for melanoma at the Washington Hospital Center between 1981 and 2000. Of
      these, 36 (6.1%) patients were African American. African American patients were
      more likely to initially be seen with stage III/IV disease (32.1%) compared with
      (12.7%) the white patients initially seen with these disease stages. Of the white
      patients 60.4% were initially seen with melanoma in situ/stage I disease compared
      with 39.3% of the African American patients. The 5-year survival rate was 58.8%
      in African Americans compared with 84.8% in whites. CONCLUSIONS: In our series,
      African Americans are more likely than whites to be initially seen with advanced
      disease and have a subsequent worse prognosis. Physician training and patient
      education campaigns are crucial to improving the poor prognosis associated with
      melanoma in the African American community.

PMID- 14699361
TI  - Primary cicatricial alopecias: clinicopathology of 112 cases.
AB  - BACKGROUND: Cicatricial alopecias represent a diverse group of diseases
      characterized by a lack of follicular ostia and irreversible alopecia. There is
      limited literature on the epidemiology and therapeutics of cicatricial alopecias.
      OBJECTIVE: The aim of this study was to review the epidemiology, clinical
      characteristics, and treatment of inflammatory cicatricial alopecias in a mixed
      ethnic population referred to a university hair clinic. METHODS: The study
      population consisted of 112 patients seen during a 5-year period with acquired
      primary cicatricial alopecias. This represented 3.2% of the total number of
      trichologic consultations seen at the University of British Columbia Hair Clinic,
      Vancouver, British Columbia, Canada. RESULTS: The ratio of lymphocytic to
      neutrophilic cicatricial alopecias was 4:1. Lymphocytic cicatricial alopecias had
      a tendency to affect middle-aged women, whereas neutrophilic cicatricial
      alopecias had a predilection for middle-aged men. CONCLUSIONS: An accurate
      diagnosis of cicatricial alopecia is achieved through careful clinicopathologic
      evaluation. We suggest that a scalp biopsy is mandatory in all cases. Multiple
      biopsies may be necessary for some affected individuals to achieve a definitive
      diagnosis as a result of a highly variable clinical course. An aggressive
      multiple modality therapeutic approach is often necessary to prevent further
      irreversible follicular destruction, implying cicatrical alopecia should be
      considered a trichologic emergency. Current therapeutic options for lymphocytic
      cicatricial alopecia include corticosteroids, antimalarials, and isotretinoin
      versus antibiotics, corticosteroids, and isotretinoin for neutrophilic
      cicatricial alopecias.

PMID- 14699362
TI  - The development of an objective method for measuring scratch in children with
      atopic dermatitis suitable for clinical use.
AB  - Itch is a major symptom of skin disease and remains poorly studied. We have used
      limb-worn digital accelerometers, and infrared video of patients as a gold
      standard, on children with atopic dermatitis and control subjects in their own
      homes at night. Video analysis shows that nocturnal scratching and restlessness
      are more complex than we first thought, with many movements that potentially
      damage the skin not conforming to stereotypical scratch movements. Children with
      atopic dermatitis spent a mean of 46 minutes less time motionless or sleeping at
      night than control subjects (468 +/- 3 [SEM] vs 422 +/- 37 [SEM], P<.001).
      Children with atopic dermatitis showed 2 to 3 times as much scratching or
      restlessness activity as control subjects, with little overlap between groups
      (P<.01). Scratching and restlessness were highly correlated with each other
      (0.94, P<.01). Accelerometer scores were highly correlated with video results
      (rho>0.02, P<.01, for scratching, restlessness, and sleeping time). Individual
      limb scores were highly correlated with each other (rho approximately 0.87-0.98),
      suggesting that little information would be lost if only 1 limb was measured.
      There was little relation between parental assessment of scratch and objective
      measured scratch. Accelerometers provide a useful and practical way of assessing
      scratching at night in the patient's own home and could be used as an objective
      measure of disease activity both in clinical trials and in everyday clinical
      practice.

PMID- 14699364
TI  - The dermatology workforce shortage.
AB  - BACKGROUND: While many dermatology workforce projections over the past two
      decades forecasted an impending oversupply, more recent reports have begun to
      suggest a shortage of dermatologic services. METHODS: Anonymous surveys
      administered to practicing dermatologists and to recent training graduates were
      examined for surrogate indicators of the supply and demand for dermatologic
      services. RESULTS: The mean wait time for new patient appointments with
      dermatologists was 36 calendar days, but ranged widely based on location (means
      ranged from 9-120 days by state). About half (49%) of practicing dermatologists
      feel that they need more dermatologists in their communities, while only 20%
      describe the local supply as too high. The reported need for medical and general
      dermatologists is far more acute than for dermatologic subspecialists. Many
      practices (33%) are looking for new associates, and not surprisingly, most new
      graduates entering the workforce over the past 4 years (86-93%) do not describe
      any difficulty finding desirable positions. Fewer than 10% of recent graduates
      are dissatisfied with their current jobs. CONCLUSION: Based on survey data
      examining wait times, physician perception, use of physician extenders, searches
      for new employees, and experience of recent graduates entering the workforce, it
      appears there is an inadequate supply of dermatologists to meet the demand for
      services.

PMID- 14699363
TI  - Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced
      phototoxicity, pigmentation, and damage of human skin.
AB  - BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II
      is limited by side effects of acute phototoxicity and possible long-term
      carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL)
      extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and
      histologic level. METHODS: A total of 10 healthy patients with skin phototypes II
      to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to
      PUVA with 7.5 mg/kg of oral PL. RESULTS: Clinically, phototoxicity was always
      lower in PL-treated skin after 48 to 72 hours (P<.005), and pigmentation was also
      reduced 4 months later. Histologically, PL-treated skin showed a significant
      numeric reduction of sunburn cells (P=.05), preservation of Langerhans cells (P<
      or =.01), decrease of tryptase-positive mast cell infiltration (P<.05), and
      decrease of vasodilation (P< or =.01). No differences were found in Ki-67+
      proliferating cells. CONCLUSIONS: PL is an effective chemophotoprotector against
      PUVA-induced skin phototoxicity and leads to substantial benefits of skin
      protection against damaging effects of PUVA as evidenced by histology.

PMID- 14699365
TI  - Photoinduced pompholyx: a report of 5 cases.
AB  - We describe 5 patients whose histories and investigation findings point toward a
      diagnosis of photo-induced hand pompholyx, a previously unreported condition.
      Several factors have been associated with the exacerbation of pompholyx, but no
      direct relationship with sunlight exposure has been reported.

PMID- 14699366
TI  - Does wrist nerve block influence the result of botulinum toxin A treatment in
      palmar hyperhidrosis?
AB  - Treatment of palmar hyperhidrosis with intracutaneous injections of botulinum
      toxin type A is painful, making anesthesia desirable. However, nerve blocks may
      be associated with reduced efficacy. In 20 patients with idiopathic palmar
      hyperhidrosis both palms were treated with intracutaneous injections of botulinum
      toxin type A after having randomly chosen one hand for anesthesia by median und
      ulnar nerve block and the other hand for cooling. There was no difference in
      efficacy of botulinum toxin A treatment between both palms but significantly
      greater injection pain after cooling compared with nerve block.

PMID- 14699367
TI  - Clinical study of repigmentation patterns with different treatment modalities and
      their correlation with speed and stability of repigmentation in 352 vitiliginous
      patches.
AB  - Because the etiopathogenesis of depigmentation in vitiligo is still obscure, the
      source of pigmentation in the repigmentating lesion and its stability is also not
      fully known. Several authors have shown on histopathology and electron microscopy
      predominantly a perifollicular spread of pigment. The aim of this study was to
      clinically assess the types of repigmentation patterns obtained with different
      treatment modalities and their correlation with speed and stability of
      repigmentation. A total of 125 patients with vitiligo on treatment with psoralens
      (topical and systemic psoralen-UVA [PUVA]), steroids (both topical and systemic),
      and topical calcipotriol, alone or in combination were enrolled. Representative
      lesions of vitiligo excluding mucosal sites were selected in each patient and
      photographed at baseline. Repigmentation was assessed and labeled as marginal,
      perifollicular, diffuse, or combined. The preselected patches were evaluated at 3
      months to assess the speed of repigmentation. Retention of pigment (stability)
      was noted at 6 months, after the stoppage of active treatment. Of the 352
      vitiligo patches selected, 194 (55%) showed predominant perifollicular
      repigmentation, of which a majority (127; 65.5%) were on systemic PUVA and 35
      (18%) were on topical PUVA. Diffuse pigmentation was observed in 98 patches
      (27.8%) of which 66 (67.3%) were on topical steroids. Marginal repigmentation was
      seen in 15, of which the majority (80%) were on systemic PUVA and topical
      calcipotriol. Of the 28 total lesions showing marked repigmentation at 3 months,
      22 lesions pigmented in a diffuse manner, 2 in a perifollicular pattern, and 4
      showed a combined type of repigmentation. On follow-up, marginal repigmentation
      was the most stable (93.3%), followed by perifollicular (91.7%) and combined type
      (84.4%). Diffuse repigmentation was the least stable (78.5%). Psoralens
      predominantly exhibit a perifollicular pattern of repigmentation and steroids
      (topical/systemic), a diffuse type. The speed of repigmentation is much faster
      when initial repigmentation is of the diffuse type as compared with follicular
      repigmentation. The marginal and perifollicular repigmentation is more stable
      than the diffuse type of repigmentation.

PMID- 14699368
TI  - Comparison of localized high-dose UVA1 irradiation versus topical cream psoralen
      UVA for treatment of chronic vesicular dyshidrotic eczema.
AB  - BACKGROUND: Vesicular dyshidrotic palmoplantar eczema is a common disorder but
      treatment is difficult. Localized photochemotherapy (cream psoralen-UVA [PUVA])
      has widely been used for therapy. Although the efficacy of cream PUVA therapy is
      well known, potential side effects may occur. Therefore, a more standardized safe
      and effective UV therapy should be carried out. OBJECTIVE: This study compared
      the effects of localized high-dose UVA1 irradiation versus topical cream PUVA for
      treatment of chronic vesicular dyshidrotic eczema. METHODS: On the basis of the
      assessment of the Dyshidrotic Area and Severity Index, the decrease of score
      points on the UVA1-treated side was compared with the decrease on the cream PUVA
      treated side in 27 patients. In addition, analysis of serum markers was
      performed. RESULTS: Of 27 patients, 24 showed a good response to localized UVA1
      irradiation or cream PUVA. Dyshidrotic Area and Severity Index scores
      significantly decreased on both sides and were reduced to half of the
      pretreatment values. No statistically significant differences between localized
      UVA1 irradiation or cream PUVA could be detected. CONCLUSION: This study
      demonstrates that localized UVA1 phototherapy is easy to perform and appears to
      be an effective and safe treatment for vesicular dyshidrotic eczema.

PMID- 14699369
TI  - Utility of fully buried horizontal mattress sutures.
AB  - BACKGROUND: Deep absorbable stitches should provide a firm closure, hemostasis,
      and good wound-edge eversion, but this is not always achieved with standard
      techniques. OBJECTIVE: We sought to investigate alternative techniques that can
      rapidly and reliably achieve these results. METHODS: We evaluated the fully
      buried horizontal mattress suture. We compared this technique with the previously
      described fully buried vertical mattress, partially buried mattresses, and
      standard reticular dermal and subcutaneous sutures. RESULTS: The fully buried
      horizontal mattress can provide excellent wound-edge approximation and eversion.
      It is particularly useful for shallow defects and narrow spaces where a deep
      stitch is required but technically difficult to insert. Overall, this method
      offers excellent final cosmesis, and individual sutures can be quickly and
      reproducibly placed with minimal practice. For very deep defects that require
      dead-space closure, the fully buried vertical mattress may be preferable.
      CONCLUSIONS: The buried horizontal mattress suture has wide applicability as the
      buried stitch in a bilayer repair.

PMID- 14699370
TI  - Parakeratosis.
AB  - The diagnostic value of parakeratosis is reviewed, with special emphasis on
      associated inflammatory tissue reaction patterns and the geometric pattern of the
      scale. Parakeratosis may also occur in disorders not primarily inflammatory in
      nature and those associations are addressed. Topics are divided into 6
      categories: parakeratosis in the settings of spongiotic and interface dermatitis,
      disorders in which neutrophils are a prominent feature, "patterned"
      parakeratosis, parapsoriasis, and disorders of keratinization. The entities
      considered are diverse and major diagnostic features of each are reviewed.

PMID- 14699371
TI  - Medicare, Medicaid, and access to dermatologists: the effect of patient insurance
      on appointment access and wait times.
AB  - BACKGROUND: In 2002, the Centers for Medicare and Medicaid Services implemented a
      5.4% cut in Medicare physician payments, and further reductions are expected in
      2004. These cuts have raised concerns that beneficiaries of Medicare will face
      significant problems obtaining needed physician services. Although there is clear
      evidence of poor access to care for patients with Medicaid, data measuring access
      to physicians for patients with Medicare are sparse. Given current lengthy
      appointment wait times resulting from a relative shortage of dermatologists, we
      hypothesized that patients with lower-paying coverage might be more likely to
      experience appointment refusals, longer wait times, or both. METHODS: Because the
      ability to obtain timely appointments is a key measure of access, we surveyed
      dermatologists in 12 medium- and large-sized communities to assess wait times for
      routine new-patient visits. Dermatologists in these areas (or their staff)
      received a telephone call asking about the next available appointment for a
      hypothetical patient with a randomly assigned insurance type (ie, Medicaid,
      Medicare, or fee-for-service private insurance). RESULTS: Of 631 physicians (or
      staff members) contacted, 612 (97%) agreed to participate. Overall acceptance
      rates were similar for patients with Medicare (85%) and private insurance (87%),
      but were much lower for those with Medicaid (32%). Among patients whose insurance
      was accepted, mean wait times for patients with Medicare and private insurance
      were 37 days, but patients with Medicaid experienced significant queuing (50
      days). There was dramatic geographic variation. In areas where Medicare payments
      are low relative to commercial payers, there were increases in Medicare rejection
      rates and wait times. In communities with relatively low Medicaid payment rates,
      patients with Medicaid faced higher rejection rates and longer wait times. There
      were also longer overall wait times for female dermatologists and in communities
      where the concentration of dermatologists was low. CONCLUSION: Although overall
      access to dermatologists appears comparable for patients with Medicare and
      private insurance, some access limitations in "hot spots" where Medicare payments
      are low relative to commercial insurers suggest that patients in these areas may
      be most sensitive to further payment reductions. Significant access problems for
      beneficiaries of Medicaid, particularly in areas where Medicaid payments are
      relatively low, may be a harbinger of the potential consequences of sustained
      declines in Medicare physician reimbursement.

PMID- 14699372
TI  - Tickle.
AB  - Tickle is a familiar sensation that may have two components: a light or feather
      type noxious sensation termed by Hall and Allin as knismesis, and a heavy or
      laughter-associated sensation termed gargalesis. Studies on the sensation of
      tickle have generally been on one sensation or the other, but not on both. In
      pleasurable, laughter-associated tickle there are elements of touch and pleasure,
      but the sensation may be a synthesis of touch and itch, with receptors, neural
      pathways or central receptors different from knismesis. It is unclear why some
      skin sites are more ticklish than other sites. Laughter-associated tickle might
      best be considered a social behavior rather than a reflex. This behavior provides
      interaction between mother and child, helps to integrate a child with peers and
      adults in play, and may become part of the mating ritual or sexual foreplay. In
      tickle play there are elements of dominance and submission, with accompanying
      laughter and withdrawal developed as the signals of submission. In this scenario,
      ticklish areas of skin might be considered those areas most vital to the ticklee
      and allowed to be invaded in the dominance submission play.

PMID- 14699373
TI  - Surgical Pearl: immobilization of the helical rim for postauricular procedures.

PMID- 14699374
TI  - Surgical Pearl: full-thickness punch grafting in chronic nonhealing ulcers.

PMID- 14699375
TI  - Treatment of lentigo maligna with tazarotene 0.1% gel.
AB  - We report 2 elderly patients with facial lentigo maligna who experienced complete
      regression, both clinically and histopathologically, after once-daily topical
      treatment with tazarotene 0.1% gel for 6 to 8 months. After a follow-up period of
      18 and 30 months, no recurrence was observed. We believe that tazarotene might be
      considered as an alternative medical approach in selected patients with lentigo
      maligna.

PMID- 14699376
TI  - Increased incidence of hypercoagulability in patients with leg ulcers caused by
      leukocytoclastic vasculitis.
AB  - Vasculitis is a rare cause of leg ulceration. It is unclear why severe skin
      infarction develops in some patients with vasculitis, whereas others have only
      mild symptoms such as purpura, erythema, or urticaria. A coincidence of
      vasculitis and hypercoagulability may lead to more extensive thrombotic occlusion
      and hence explain the occurrence of large ulcers in a subset of patients. Our aim
      was to investigate whether patients with vasculitis ulcers have an increased
      incidence of hypercoagulability. Thirteen consecutive patients admitted to the
      hospital with necrotic ulcers caused by histologically confirmed vasculitis were
      screened for clotting disorders. In 7 of 13 patients (53%), hypercoagulable
      conditions were found. Five patients had factor V Leiden (38%), and 2 had lupus
      anticoagulant (15%). The normal frequency of these conditions is 5% to 6% and
      3.6%, respectively. These data indicate that there is an increased incidence of
      hypercoagulable disorders in patients with vasculitis ulcers. We recommend
      screening these patients routinely for hypercoagulability.

PMID- 14699377
TI  - Tacrolimus effect on rosacea.
AB  - Twenty-four patients with erythrotelangiectatic or papulopustular rosacea were
      treated with 0.1% tacrolimus topical ointment in a 12-week open-label trial.
      Erythema was significantly improved in both rosacea subtypes (P<.05). There was
      no decrease in the number of papulopustular lesions. Side effects were consistent
      with those on the tacrolimus topical ointment labeling.

PMID- 14699378
TI  - UV light-induced linear IgA dermatosis.
AB  - Various exogenous factors (eg, drugs, dietary antigens, trauma, infections,
      radiographs, and UV radiation) are known to induce or aggravate skin diseases. UV
      radiation in particular is known to induce or aggravate the autoimmune bullous
      diseases of pemphigus foliaceus, pemphigus vulgaris, and bullous pemphigoid. Its
      role in linear IgA dermatosis, however, is not well recognized. We report the
      second case of linear IgA dermatosis induced by intense sun exposure in which
      blistering was induced by UVA radiation. Furthermore, a review of the literature
      on photoinduced autoimmune bullous diseases and the wavelengths responsible for
      the induction of blistering is presented and several proposed mechanisms of
      action for the blister induction, including release or unmasking of antigens,
      promotion of antibody fixation by UV radiation, and launching of an inflammatory
      process, are discussed. We conclude that linear IgA dermatosis should be added to
      the list of autoimmune bullous diseases induced and/or aggravated by UV
      radiation.

PMID- 14699379
TI  - Generalized eruptive histiocytosis.
AB  - The histiocytic disorders can be broadly categorized into histiocytosis X
      (Langerhans cell-derived) and non-X types. There are several variants of non-X
      histiocytoses that tend to occur in a generalized distribution on the body; these
      include xanthoma disseminatum, generalized eruptive histiocytosis (GEH),
      progressive nodular histiocytosis, and multicentric reticulohistiocytosis.
      Clinical and pathologic correlation are required for differentiating among these
      4 disorders. We report a case of a middle-aged man in whom small, scattered,
      symmetrical lesions on the trunk and proximal extremities developed that, after
      correlating with biopsy specimen and laboratory results, were best classified as
      a non-X histiocytosis with features of GEH. GEH is a rare generalized non-X
      histiocytosis that occurs mainly in adults. It is characterized by multiple,
      scattered, symmetric lesions on the trunk and proximal extremities that are
      benign in nature and tend to resolve spontaneously. Recent literature has
      suggested that GEH may be a part of a continuous spectrum of non-X histiocytic
      disorders.

PMID- 14699380
TI  - Self-healing papular mucinosis in an adult.
AB  - Papular mucinosis is a rare, idiopathic cutaneous mucinosis that is typically
      chronic and progressively severe. We present a case of a 59-year-old woman with a
      6-month history of a dramatic papular eruption on her face and neck, with no
      associated internal organ involvement. A biopsy specimen demonstrated increased
      dermal mucin with associated plump fibroblasts, consistent with a diagnosis of
      papular mucinosis. Multiple therapeutic interventions were unsuccessful, and
      after 2 years the lesions resolved spontaneously without treatment. During the
      following 3 years, the patient has had no recurrence of disease.

PMID- 14699381
TI  - A rapidly growing eccrine poroma in a pregnant woman.
AB  - A variety of tumors develop or exacerbate during pregnancy and it is well known
      that a noticeable increase of eccrine activity occurs in this period. Eccrine
      poroma is a benign neoplasm that originates from the eccrine sweat gland. The
      development of this tumor during pregnancy is extremely infrequent. We report a
      rare case of rapidly growing eccrine poroma in an unusual location (the nose) in
      a pregnant woman.

PMID- 14699382
TI  - Multiple elastofibromas.
AB  - Elastofibroma is an uncommon fibroelastic tumor or tumorlike process that usually
      occurs between the scapula and the chest wall of elderly patients. This condition
      is rarely reported in the dermatologic literature, because it infrequently arises
      in the skin or within the subcutaneous tissue. We present a 78-year-old man with
      15 separate subcutaneous nodules on the buttocks and upper extremities together
      with bilateral subscapular nodules. All specimens taken from different lesions
      were histologically confirmed as elastofibromas. As far as we know, this case
      with 17 distinct elastofibromas demonstrates the largest number ever reported in
      a single patient. Although the pathomechanism of the occurrence of multiple
      elastofibromas is unknown, it should be included in the differential diagnosis of
      multiple subcutaneous nodules.

PMID- 14699383
TI  - Neurothekeoma: report of a case in an infant and review of the literature.
AB  - Neurothekeomas (nerve sheath myxomas) are uncommon benign tumors of nerve sheath
      origin. We describe an infant with a neurothekeoma and review the literature of
      neurothekeomas in children and adults. Neurothekeomas have been reported in 292
      patients whose ages have ranged from 15 months to 84 years. They occur twice as
      often in women as in men. Neurothekeomas were most commonly located on the upper
      extremities and the head and neck. They also occurred on the trunk, the lower
      extremities, and mucosa. Histologic variants of neurothekeomas include classical,
      cellular, and mixed tumors. Surgical excision was the most common treatment.
      Recurrences were attributed to an incomplete excision; treatment of these tumors
      is by complete excision. Neurothekeomas should be included in the differential
      diagnosis of dermal nodules in infants and children.

PMID- 14699384
TI  - Superficial acral fibromyxoma of the index finger.
AB  - We describe a patient with a superficial acral fibromyxoma, the first such case
      in the dermatology literature, and review its clinical and histopathologic
      characteristics.

PMID- 14699385
TI  - Oral pemphigus vulgaris after anthrax vaccine administration: association or
      coincidence?
AB  - Pemphigus vulgaris is an autoimmune blistering disorder of the skin and mucous
      membranes. Numerous medications, ultraviolet light, and radiation have all been
      implicated in the etiology of the disease. We present a patient with pemphigus
      vulgaris whose disease developed after administration of anthrax vaccine. The
      histologic and immunofluorescence findings were characteristic of pemphigus
      vulgaris. Adverse systemic events associated with the anthrax vaccine consist
      primarily of flu-like symptoms. Previous cases of pemphigus vulgaris associated
      with anthrax vaccine administration have not been reported. Considering the
      recent deliberate outbreaks of anthrax and continued threats of bioterrorism, the
      potential exists for widespread administration of the anthrax vaccine.
      Accordingly, continued observation and documentation of true adverse events is
      needed.

PMID- 14699386
TI  - Autoinoculation vaccinia.

PMID- 14699388
TI  - Medical and dermatology dictionaries: an examination of unstructured definitions
      and a proposal for the future.
AB  - Medical dictionaries serve to describe and clarify the term set used by medical
      professionals. In this commentary, we analyze a representative set of skin
      disease definitions from 2 prominent medical dictionaries, Stedman's Medical
      Dictionary and Dorland's Illustrated Medical Dictionary. We find that there is an
      apparent lack of stylistic standards with regard to content and form. We advocate
      a new standard form for the definition of medical terminology, a standard to
      complement the easy-to-read yet unstructured style of the traditional dictionary
      entry. This new form offers a reproducible structure, paving the way for the
      development of a computer readable "dictionary" of medical terminology. Such a
      dictionary offers immediate update capability and a fundamental improvement in
      the ability to search for relationships between terms.

PMID- 14699390
TI  - Development of Kaposi's sarcoma in an AIDS patient after treatment with topical
      tacrolimus.

PMID- 14699391
TI  - Contact dermatitis from Rhus toxicodendron in a homeopathic remedy.

PMID- 14699392
TI  - Fungus-free versus disease-free nails.

PMID- 14699393
TI  - Treatment of dyshidrotic hand dermatitis with intradermal botulinum toxin.

PMID- 14699394
TI  - Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.
AB  - BACKGROUND: IL-5 is a cytokine critically involved in regulating several aspects
      of eosinophils including their production, activation, and tissue recruitment. As
      such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a
      group of poorly treated diverse disorders characterized by sustained peripheral
      blood and/or tissue eosinophilia. OBJECTIVE: We aimed to assess the safety and
      efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab)
      in patients with several forms of hyper-eosinophilic syndromes. METHODS: We
      performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10
      mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with
      hypereosinophilic syndromes (defined by peripheral blood and/or tissue
      eosinophilia). The effects of treatment on safety, eosinophil levels (in
      peripheral blood and/or diseased tissue), pulmonary function, and quality of life
      were measured over a 28-week period. RESULTS: Anti-IL-5 was well tolerated in all
      patients and lowered peripheral blood eosinophil counts despite ongoing systemic
      glucocorticoid therapy. The decline in circulating eosinophil counts was
      sustained for at least 12 weeks after the last dose of anti-IL-5. In addition,
      anti-IL-5 improved clinical and quality of life measurements. In one patient with
      striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a
      10-fold reduction in tissue eosinophil levels. CONCLUSIONS: These results suggest
      that anti-IL-5 is safe, effective in lowering eosinophil levels, and has
      potential glucocorticoid-sparing effects in patients with a variety of hyper
      eosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic
      potential for hypereosinophilic syndromes.

PMID- 14699395
TI  - Incorporating the Internet.

PMID- 14699396
TI  - A cancer immunosurveillance controversy.

PMID- 14699398
TI  - Dendritic cells: a journey from laboratory to clinic.

PMID- 14699399
TI  - Genes tell lymphatics to sprout or not.

PMID- 14699400
TI  - Lymphoid organogenesis: getting the green light from RORgamma(t).

PMID- 14699401
TI  - ComPPARtmentalizing NF-kappaB in the gut.

PMID- 14699402
TI  - Mindin the fort.

PMID- 14699403
TI  - How resting T cells deMURR HIV infection.

PMID- 14699405
TI  - Human primary immunodeficiency diseases: a perspective.
AB  - Primary immunodeficiency diseases consist of a group of more than 100 inherited
      conditions, mostly monogenic, predisposing individuals to different sets of
      infections, allergy, autoimmunity and cancer. Primary immunodeficiencies
      therefore represent exquisite models of various immunopathological settings. The
      identification of the associated genes, 100 so far, has generated a plethora of
      information about the immune system and spurred the analysis of many aspects of
      the development, function and regulation of both innate and adaptive immunity.
      These findings can potentially contribute to improved care of affected
      individuals by providing new diagnostic and/or therapeutic tools.

PMID- 14699407
TI  - Better reading through brain research.

PMID- 14699409
TI  - Beyond simulation? Neural mechanisms for predicting the actions of others.

PMID- 14699410
TI  - Developing neurons make the switch.

PMID- 14699411
TI  - Adaptation and attentional selection.

PMID- 14699412
TI  - How does practice makes perfect?

PMID- 14699413
TI  - The site of saccadic suppression.
AB  - During rapid eye movements, or saccades, stable vision is maintained by active
      reduction of visual sensitivity. The site of this saccadic suppression remains
      uncertain. Here we show that phosphenes--small illusory visual perceptions-
      induced by transcranial magnetic stimulation (TMS) to the human occipital cortex
      are immune to saccadic suppression, whereas phosphenes induced by retinal
      stimulation are not, thus providing direct physiological evidence that saccadic
      suppression occurs between the retina and the occipital visual cortex.

PMID- 14699414
TI  - Binding personal and extrapersonal space through body shadows.
AB  - Shadows in visual scenes can have profound effects on visual perception. Here we
      have found that visual distracters distant from the body interfere with human
      spatial discrimination of tactile targets at a hand, particularly when the shadow
      of the stimulated hand stretches toward them in extrapersonal space. These
      findings suggest that shadows cast by a person's own body parts can bridge the
      gap between personal and extrapersonal space.

PMID- 14699415
TI  - Developmental switch from GABA to glycine release in single central synaptic
      terminals.
AB  - Early in postnatal development, inhibitory inputs to rat lateral superior olive
      (LSO) neurons change from releasing predominantly GABA to releasing predominantly
      glycine into the synapse. Here we show that spontaneous miniature inhibitory
      postsynaptic currents (mIPSCs) also change from GABAergic to glycinergic over the
      first two postnatal weeks. Many 'mixed' mIPSCs, resulting from co-release of
      glycine and GABA from the same vesicles, are seen during this transition.
      Immunohistochemistry showed that a large number of terminals contained both GABA
      and glycine at postnatal day 8 (P8). By P14, both the content of GABA in these
      mixed terminals and the contribution of GABA to the mixed mIPSCs had decreased.
      The content of glycine in terminals increased over the same period. Our results
      indicate that switching from GABAergic to glycinergic inputs to the LSO may occur
      at the level of a single presynaptic terminal. This demonstrates a new form of
      developmental plasticity at the level of a single central synapse.

PMID- 14699416
TI  - Hippocampal plasticity requires postsynaptic ephrinBs.
AB  - Chemical synapses contain specialized pre- and postsynaptic structures that
      regulate synaptic transmission and plasticity. EphB receptor tyrosine kinases are
      important molecular components in this process. Previously, EphB receptors were
      shown to act postsynaptically, whereas their transmembrane ligands, the ephrinBs,
      were presumed to act presynaptically. Here we show that in mouse hippocampal CA1
      neurons, the Eph/ephrin system is used in an inverted manner: ephrinBs are
      predominantly localized postsynaptically and are required for synaptic
      plasticity. We further demonstrate that EphA4, a candidate receptor, is also
      critically involved in long-term plasticity independent of its cytoplasmic
      domain, suggesting that ephrinBs are the active signaling partner. This work
      raises the intriguing possibility that depending on the type of synapse,
      Eph/ephrins can be involved in activity-dependent plasticity in converse ways,
      with ephrinBs on the pre- or the postsynaptic side.

PMID- 14699417
TI  - BDNF is necessary and sufficient for spinal respiratory plasticity following
      intermittent hypoxia.
AB  - Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in
      the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that
      increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal
      cord is necessary and sufficient for pLTF in adult rats. We found that
      intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in
      ventral spinal segments containing the phrenic nucleus, and the magnitude of
      these BDNF increases correlated with pLTF magnitude. We used RNA interference
      (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition
      to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal
      injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate
      new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new
      therapeutic strategies for treating breathing disorders such as respiratory
      insufficiency after spinal injury. These experiments also illustrate the
      potential use of RNAi to investigate functional consequences of gene expression
      in the mammalian nervous system in vivo.

PMID- 14699418
TI  - Neuron-specific contribution of the superior colliculus to overt and covert
      shifts of attention.
AB  - The analysis of a peripheral visual location can be improved in two ways: either
      by orienting one's gaze (usually by making a foveating saccade) or by 'covertly'
      shifting one's attention to the peripheral location without making an eye
      movement. The premotor theory of attention holds that saccades and spatial shifts
      of attention share a common functional module with a distinct neuronal basis.
      Using single-unit recording from the brains of trained rhesus monkeys, we
      investigated whether the superior colliculus, the major subcortical center for
      the control of saccades, is part of this shared network for attention and
      saccades. Here we show that a distinct type of neuron in the intermediate layer
      of the superior colliculus, the visuomotor neuron, which is known to be centrally
      involved in the preparation of saccades, is also active during covert shifts of
      attention.

PMID- 14699419
TI  - Increased prefrontal and parietal activity after training of working memory.
AB  - Working memory capacity has traditionally been thought to be constant. Recent
      studies, however, suggest that working memory can be improved by training. In
      this study, we have investigated the changes in brain activity that are induced
      by working memory training. Two experiments were carried out in which healthy,
      adult human subjects practiced working memory tasks for 5 weeks. Brain activity
      was measured with functional magnetic resonance imaging (fMRI) before, during and
      after training. After training, brain activity that was related to working memory
      increased in the middle frontal gyrus and superior and inferior parietal
      cortices. The changes in cortical activity could be evidence of training-induced
      plasticity in the neural systems that underlie working memory.

PMID- 14699420
TI  - A system in the human brain for predicting the actions of others.
AB  - The ability to attribute mental states to others, and therefore to predict
      others' behavior, is particularly advanced in humans. A controversial but
      untested idea is that this is achieved by simulating the other person's mental
      processes in one's own mind. If this is the case, then the same neural systems
      activated by a mental function should re-activate when one thinks about that
      function performed by another. Here, using functional magnetic resonance imaging
      (fMRI), we tested whether the neural processes involved in preparing one's own
      actions are also used for predicting the future actions of others. We provide
      compelling evidence that areas within the action control system of the human
      brain are indeed activated when predicting others' actions, but a different
      action sub-system is activated when preparing one's own actions.

PMID- 14699422
TI  - Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a
      susceptibility locus for schizophrenia and psychosis.
AB  - Schizophrenia is a common psychiatric disorder with a complex genetic etiology.
      To understand the genetic basis of this syndrome in Portuguese Island
      populations, we performed a genome-wide scan of 29 families with schizophrenia,
      which identified a single region on 5q31-5q35 with strong linkage (NPL=3.09,
      P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of
      NPL=3.10 for significant linkage. Additional support for this locus in
      schizophrenia comes from higher-density mapping and mapping of 11 additional
      families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at
      markers D5S2112-D5S820. These data and previous linkage findings from other
      investigators provide strong and consistent evidence for this genomic region as a
      susceptibility locus for schizophrenia. Exploratory analyses of a novel
      phenotype, psychosis, in families with schizophrenia and bipolar disorder
      detected evidence for linkage to the same markers as found in schizophrenia (peak
      NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for
      the psychotic symptoms observed in both diseases. Molecular Psychiatry (2004) 9,
      213-218. doi:10.1038/sj.mp.4001418 Published online 30 December 2003

PMID- 14699423
TI  - Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a
      positional candidate for attention-deficit/hyperactivity disorder in the 16p13
      region.
AB  - The glutamate system may be involved in the development of attention
      deficit/hyperactivity disorder (ADHD) based on animal models and the role of N
      methyl-D-aspartate receptors (NMDAR) in cognition and motor processes. A follow
      up study of the first genome scan for ADHD identified significant evidence for
      linkage to the 16p13 region. The glutamate receptor, ionotropic, N-methyl D
      aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor,
      resides in this region and a recent study has reported an association between
      this gene and ADHD. We tested for linkage between the alleles and haplotypes of
      four polymorphisms at the GRIN2A locus and ADHD in our sample of 183 nuclear
      families with 229 affected children. In contrast to previous findings, we did not
      identify any evidence for a relationship of these markers and ADHD. Owing to the
      role of GRIN2A in aspects of cognition, we investigated the relationship of this
      gene to the cognitive phenotypes of inhibitory control, verbal short-term memory
      and verbal working memory. There was no significant evidence of linkage between
      GRIN2A and these phenotypes. While the results were not significant in our
      sample, the previous association finding suggests that further study of this gene
      is warranted.

PMID- 14699424
TI  - No association with the neuregulin 1 haplotype to Japanese schizophrenia.

PMID- 14699425
TI  - Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association
      between IMPA2 promoter polymorphisms and bipolar disorder.
AB  - Manic-depressive (bipolar) illness is a serious psychiatric disorder with a
      strong genetic predisposition. The disorder is likely to be multifactorial and
      etiologically complex, and the causes of genetic susceptibility have been
      difficult to unveil. Lithium therapy is a widely used pharmacological treatment
      of manic-depressive illness, which both stabilizes the ongoing episodes and
      prevents relapses. A putative target of lithium treatment has been the inhibition
      of the myo-inositol monophosphatase (IMPase) enzyme, which dephosphorylates myo
      inositol monophosphate in the phosphatidylinositol signaling system. Two genes
      encoding human IMPases have so far been isolated, namely myo-inositol
      monophosphatase 1 (IMPA1) on chromosome 8q21.13-21.3 and myo-inositol
      monophosphatase 2 (IMPA2) on chromosome 18p11.2. In the present study, we have
      scanned for DNA variants in the human IMPA1 and IMPA2 genes in a pilot sample of
      Norwegian manic-depressive patients, followed by examination of selected
      polymorphisms and haplotypes in a family-based bipolar sample of Palestinian Arab
      proband-parent trios. Intriguingly, two frequent single-nucleotide polymorphisms
      (-461C>T and -207T>C) in the IMPA2 promoter sequence and their corresponding
      haplotypes showed transmission disequilibrium in the Palestinian Arab trios. No
      association was found between the IMPA1 polymorphisms and bipolar disorder,
      neither with respect to disease susceptibility nor with variation in lithium
      treatment response. The association between manic-depressive illness and IMPA2
      variants supports several reports on the linkage of bipolar disorder to
      chromosome 18p11.2, and sustains the possible role of IMPA2 as a susceptibility
      gene in bipolar disorder.

PMID- 14699426
TI  - Association of SNPs and haplotypes in GABAA receptor beta2 gene with
      schizophrenia.
AB  - Disturbances in GABAergic system have been observed in schizophrenics. In the
      present study, population association analysis was performed on 19 SNPs in the
      alpha(1), beta(2), gamma(2), epsilon and pi subunit genes of GABA(A) receptor.
      Five SNPs in GABRB2, namely B2I7G1584T, rs1816071, rs194072, rs252944 and
      rs187269, were found to be significantly associated, and their haplotypes in
      linkage disequilibrium, with schizophrenia. This represents the first report on
      any disease association of SNPs in the human GABA(A) receptor genes, and focuses
      attention on the GABAergic hypothesis of schizophrenia etiology.

PMID- 14699427
TI  - Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory
      impairment induced by central administration of interleukin-1beta in rats.
AB  - Central or peripheral administration of the proinflammatory cytokine interleukin
      (IL)-1beta can impair performance on spatial memory tasks and also elevate
      circulating concentration of corticosterone. The present experiment provides
      independent confirmation that intracerebroventricular administration of 10 ng IL
      1beta in the rat can have a selective effect on the retrieval of trial unique
      information about the location of food on an eight-arm radial maze. The probable
      involvement of corticosterone in IL-1beta-induced memory impairment was indicated
      by elevated corticosterone levels after IL-1beta administration. Further evidence
      comes from the blockade of the associated impairment in working memory by
      coadministration of the glucocorticoid receptor antagonist RU486. Ingestion of
      diet containing omega-3 fatty acid eicosapentaenoic acid (EPA) is known to
      antagonize the synthesis of prostaglandin (PG) E2 from aracadonic acid, and the
      present study confirmed that ethyl EPA (1%) reduced IL-1beta-elevated
      concentrations of PGE2 and corticosterone. Furthermore, rats given the ethyl-EPA
      diet for 8 weeks were unaffected by the disruptive effects of IL-1beta on working
      memory. IL-1beta-induced suppression of mitogen-stimulated release of the anti
      inflammatory cytokine IL-10 was also blocked by treatment with ethyl-EPA.
      Collectively, these data demonstrate that IL-1beta can impair memory function by
      elevating the concentration of corticosterone and that prior consumption of 1%
      ethyl-EPA can block both the neuroendocrine and cognitive effects of IL-1beta.
      These findings in turn may indicate beneficial effects of ethyl-EPA in the
      treatment of cognitive and affective disorders in which inflammation and stress
      play a critical role.

PMID- 14699428
TI  - Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of
      neurogenesis in a mouse model of depression.
AB  - Repeated exposure to stress is known to induce structural remodelling and
      reduction of neurogenesis in the dentate gyrus. Corticotrophin-releasing factor
      (CRF) and vasopressin (AVP) are key regulators of the stress response via
      activation of CRF(1) and V(1b) receptors, respectively. The blockade of these
      receptors has been proposed as an innovative approach for the treatment of
      affective disorders. The present study aimed at determining whether the CRF(1)
      receptor antagonist SSR125543A, the V(1b) receptor antagonist SSR149415, and the
      clinically effective antidepressant fluoxetine may influence newborn cell
      proliferation and differentiation in the dentate gyrus of mice subjected to the
      chronic mild stress (CMS) procedure, a model of depression with predictive
      validity. Repeated administration of SSR125543A (30 mg/kg i.p.), SSR149415 (30
      mg/kg i.p.), and fluoxetine (10 mg/kg i.p.) for 28 days, starting 3 weeks after
      the beginning of the stress procedure, significantly reversed the reduction of
      cell proliferation produced by CMS, an effect which was paralleled by a marked
      improvement of the physical state of the coat of stressed mice. Moreover, mice
      subjected to stress exhibited a 53% reduction of granule cell neurogenesis 30
      days after the end of the 7-week stress period, an effect which was prevented by
      all drug treatments. Collectively, these results point to an important role of
      CRF and AVP in the regulation of dentate neurogenesis, and suggest that CRF(1)
      and V(1b) receptor antagonists may affect plasticity changes in the hippocampal
      formation, as do clinically effective antidepressants.

PMID- 14699429
TI  - Linkage analysis for autism in a subset families with obsessive-compulsive
      behaviors: evidence for an autism susceptibility gene on chromosome 1 and further
      support for susceptibility genes on chromosome 6 and 19.
AB  - Although there is considerable evidence for a strong genetic component to
      idiopathic autism, several genome-wide screens for susceptibility genes have been
      carried out with limited concordance of linked loci, reflecting numerous genes of
      weak effect and/or sample heterogeneity. In the current study, linkage analysis
      was carried out in a sample of 62 autism-affected relative pairs with more severe
      obsessive-compulsive behaviors, selected from a larger (n=115) set of autism
      affected relative pairs as a means of reducing sample heterogeneity. Obsessive
      compulsive behaviors were assessed using the Autism Diagnostic Interview-Revised
      (ADI-R). In the sample with more severe obsessive-compulsive behaviors,
      multipoint NPL scores above 2 were observed on chromosomes 1, 4, 5, 6, 10, 11 and
      19, with the strongest evidence for linkage on chromosome 1 at the marker
      D1S1656, where the multipoint NPL score was 3.06, and the two-point NPL score was
      3.21. In follow-up analyses, analyzing the subset of families (n=35) where the
      patients had the most severe obsessive-compulsive behaviors generated a
      multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that
      the bulk of evidence for linkage was derived from the families most severely
      affected with obsessive-compulsive behaviors. The data suggest that there is an
      autism susceptibility gene on chromosome 1 and provide further support for the
      presence of autism susceptibility genes on chromosomes 6 and 19.

PMID- 14699430
TI  - Transmission disequilibrium testing of dopamine-related candidate gene
      polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5.
AB  - Attention-deficit hyperactivity disorder (ADHD) is one of the most common
      childhood behavioral disorders. Genetic factors contribute to the underlying
      liability to develop ADHD. Reports implicate variants of genes important for the
      synthesis, uptake, transport and receptor binding of dopamine in the etiology of
      ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a
      large multiplex sample of ADHD affected children and their parents for
      polymorphisms in genes previously reported to be associated with ADHD.
      Associations were tested by the transmission disequilibrium test (TDT). The
      sample is sufficient to detect genotype relative risks (GRRs) for putative risk
      alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed
      a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as
      suggested by an analysis of a subset of these families. The seven repeat allele
      of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated
      with ADHD in the large sample in contrast to our earlier findings in a smaller
      subset. We replicate an association of a dinucleotide repeat polymorphism near
      the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele
      (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053).
      No evidence for an association was found for polymorphisms in DRD2 or DAT1 in
      this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240)
      allele of the promoter polymorphism emerge as the two DNA variants showing a
      significant association in this large sample of predominantly multiplex families
      with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.

PMID- 14699431
TI  - Functional but not structural subgenual prefrontal cortex abnormalities in
      melancholia.
AB  - Major depression is a heterogeneous condition, and the search for neural
      correlates specific to clinically defined subtypes has been inconclusive.
      Theoretical considerations implicate frontostriatal, particularly subgenual
      prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a
      subtype of depression characterized by anhedonia--but no empirical evidence has
      been found yet for such a link. To test the hypothesis that melancholic, but not
      nonmelancholic depression, is associated with the subgenual PFC impairment,
      concurrent measurement of brain electrical (electroencephalogram, EEG) and
      metabolic (positron emission tomography, PET) activity were obtained in 38
      unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18
      nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with
      a tomographic source localization method that computed the cortical three
      dimensional distribution of current density for standard frequency bands,
      allowing voxelwise correlations between the EEG and PET data. Voxel-based
      morphometry analyses of structural magnetic resonance imaging (MRI) data were
      performed to assess potential structural abnormalities in melancholia.
      Melancholia was associated with reduced activity in the subgenual PFC (Brodmann
      area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and
      decreased glucose metabolism, which themselves were inversely correlated.
      Following antidepressant treatment, depressed subjects with the largest
      reductions in depression severity showed the lowest post-treatment subgenual PFC
      delta activity. Analyses of structural MRI revealed no group differences in the
      subgenual PFC, but in melancholic subjects, a negative correlation between gray
      matter density and age emerged. Based on preclinical evidence, we suggest that
      subgenual PFC dysfunction in melancholia may be associated with blunted hedonic
      response and exaggerated stress responsiveness.

PMID- 14699432
TI  - Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in
      patients with mild cognitive impairment.
AB  - Subjects with mild cognitive impairment (MCI) are at a high risk of developing
      clinical Alzheimer's disease (AD). We asked to what extent the core biomarker
      candidates cerebro-spinal fluid (CSF) beta-amyloid(1-42) (Abeta(1-42)) and CSF
      tau protein concentrations predict conversion from MCI to AD. We studied 52
      patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group
      was composed of 29 patients who had converted to AD during follow-up, and of 23
      patients who showed no cognitive decline. CSF Abeta(1-42) and tau protein levels
      were assessed at baseline in all subjects, using enzyme-linked immunosorbent
      assays. For assessment of sensitivity and specificity, we used independently
      established reference values for CSF Abeta(1-42) and CSF tau. The levels of CSF
      tau were increased, whereas levels of Abeta(1-42) were decreased in MCI subjects.
      Abeta(1-42) predicted AD in converted MCI with a sensitivity of 59% and a
      specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and
      a specificity of 90%. In a multiple Cox regression analysis within the MCI group,
      low baseline levels of Abeta(1-42), but not other predictor variables (tau
      protein, gender, age, apolipoprotein E epsilon4 carrier status, Mini Mental
      Status Examination score, observation time, antidementia therapy), correlated
      with conversion status (P<0.05). Our findings support the notion that CSF tau and
      Abeta(1-42) may be useful biomarkers in the early identification of AD in MCI
      subjects.

PMID- 14699433
TI  - The dopamine D4 receptor is essential for hyperactivity and impaired behavioral
      inhibition in a mouse model of attention deficit/hyperactivity disorder.
AB  - The dopamine D4 receptor (D4R) is a candidate gene for attention
      deficit/hyperactivity disorder (ADHD) based on genetic studies reporting that
      particular polymorphisms are present at a higher frequency in affected children.
      However, the direct participation of the D4R in the onset or progression of ADHD
      has not been tested. Here, we generated a mouse model with high face value to
      screen candidate genes for the clinical disorder by neonatal disruption of
      central dopaminergic pathways with 6-hydroxydopamine (6-OHDA). The lesioned mice
      exhibited hyperactivity that waned after puberty, paradoxical hypolocomotor
      responses to amphetamine and methylphenidate, poor behavioral inhibition in
      approach/avoidance conflict tests and deficits in continuously performed motor
      coordination tasks. To determine whether the D4R plays a role in these behavioral
      phenotypes, we performed 6-OHDA lesions in neonatal mice lacking D4Rs (Drd4(-/
      )). Although striatal dopamine contents and tyrosine hydroxylase-positive
      midbrain neurons were reduced to the same extent in both genotypes, Drd4(-/-)
      mice lesioned with 6-OHDA did not develop hyperactivity. Similarly, the D4R
      antagonist PNU-101387G prevented hyperactivity in wild-type 6-OHDA-lesioned mice.
      Furthermore, wild-type mice lesioned with 6-OHDA showed an absence of behavioral
      inhibition when tested in the open field or the elevated plus maze, while their
      Drd4(-/-) siblings exhibited normal avoidance for the unprotected areas of these
      mazes. Together, our results from a combination of genetic and pharmacological
      approaches demonstrate that D4R signaling is essential for the expression of
      juvenile hyperactivity and impaired behavioral inhibition, relevant features
      present in this ADHD-like mouse model.

PMID- 14699434
TI  - 22q11 deletion syndrome in childhood onset schizophrenia: an update.

PMID- 14699435
TI  - A leadership crisis in American psychiatry.

PMID- 14699438
TI  - Putting a PARKINg brake on neurodegeneration.

PMID- 14699439
TI  - Association of estrogen receptor beta gene polymorphisms with bulimic disease in
      women.
AB  - In this study, we explored the potential association between estrogen receptor
      beta (ERbeta) and disease in a group of bulimic women. Eating disorders are much
      more common in females than in males, suggesting a possible role for female sex
      hormone signalling in the pathogenesis of these diseases. Furthermore, estrogen
      has been implicated in appetite regulation. The occurrence of menstrual
      disturbances is also increased in bulimic women. We studied 76 bulimic women and
      60 controls, and found an association between two common polymorphisms in the
      ERbeta gene with disease in this group of bulimic women. More detailed
      characterisation of the ERbeta gene identified a novel variant changing the
      primary structure of ERbeta protein in one bulimic patient. An initial functional
      characterization of this variant did not reveal any differences compared to the
      wild-type protein. Our findings point towards a possible role of ERbeta and/or
      neighboring genes in the etiology of disease in bulimic patients.

PMID- 14699440
TI  - Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5
      receptors.
AB  - The glutamate hypothesis of schizophrenia derived from evidence that
      phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces
      schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by
      prepulse inhibition (PPI), is a fundamental form of information processing that
      is deficient in schizophrenia patients and rodents treated with NMDA antagonists.
      Hence, PPI is widely used to study the neurobiology of schizophrenia. As the use
      of PPI as a model of gating deficits in schizophrenia has become more widespread,
      it has become increasingly important to assess such deficits accurately. Here we
      identify a possible role of mGluR5 in PPI by using wild type (WT) and mGluR5
      knockout (KO) mice of two different background strains, 129SvPasIco and C57BL/6.
      In both strains, PPI was disrupted dramatically in the mGluR5 KO mice throughout
      a range of interstimulus intervals and sensory modalities. The present findings
      further support the glutamate hypothesis of schizophrenia and identify a
      functional role for mGluR5 in sensorimotor gating.

PMID- 14699441
TI  - Modification of human 5-HT(2C) receptor function by Cys23Ser, an abundant,
      naturally occurring amino-acid substitution.
AB  - A human serotonin (5-HT)(2C) receptor gene polymorphism leads to the substitution
      of cysteine for serine at codon 23 (Cys23Ser); the frequency of the Ser23 allele
      in unrelated Caucasians is approximately 0.13. In the present study, we assessed
      whether Cys23Ser could affect receptor function. The two alleles were
      functionally compared following expression in COS-7 cells. The constitutive
      activity of the receptor in an in situ reconstitution system was also evaluated
      following expression of each allele in Sf9 cells. Using radioligands, Ser23
      expressed membranes showed reduced high-affinity binding to meta
      chlorophenylpiperazine (m-CPP) and 5-HT. Although the amplitude of the 5-HT
      induced intracellular Ca(2+) peak did not differ between the alleles, Ser23
      required higher 5-HT concentrations to elicit the same response. These
      differences might be due to more extensive desensitization in the Ser23 form. In
      the in situ reconstitution system, the 5-HT(2C) receptor displayed considerable
      constitutive activity, with the Ser23 allele being significantly higher in this
      regard than the Cys23 form. After prolonged serum deprivation in order to
      resensitize the receptor, four of the 15 cells expressing Ser23 showed abnormally
      higher m-CPP-induced sensitivity of the Ca(2+) response. These results indicate
      that the Ser23 allele may be constitutively more active than Cys23. Thus, Ser23
      appears to be an abundant candidate allele capable of directly influencing inter
      individual variation in behavior, susceptibility to mental disorder, and response
      to drugs including atypical antipsychotic and some antidepressant drugs that are
      potent 5-HT(2C) inverse agonists or antagonists.

PMID- 14699442
TI  - Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated
      protein kinase inhibits glucocorticoid receptor function.
AB  - Previous studies have demonstrated that interleukinalpha (IL-1alpha) inhibits
      glucocorticoid receptor (GR) nuclear translocation and dexamethasone (Dex)
      induced gene transcription. Given that IL-1alpha is a potent activator of the p38
      mitogen-activated protein kinase (MAPK) signal transduction pathway and p38 MAPK
      has been associated with reduced GR function, we examined the role of p38 MAPK in
      IL-1alpha-mediated inhibition of GR function in mouse fibroblast cells stably
      transfected with a GR-mediated reporter gene construct (LMCAT cells). Treatment
      of LMCAT cells with IL-1alpha (1000 U/ml) for 24 h inhibited Dex (50 nM)-induced
      GRE-CAT activity by approximately 35%. When cells were cotreated for 24 h with IL
      1alpha plus SB-203580 (0.5-1 microM), a selective p38 inhibitor, IL-1alpha's
      inhibitory effect on GR function as determined by Dex-induced GRE-CAT activity
      was reversed. Using gel mobility shift assay, SB-203580 was also found to reverse
      IL-1alpha inhibition of GR-GRE binding. Further confirming the role of p38
      pathways, pretreatment of LMCAT cells with antisense oligonucleotides targeted to
      p38 MAPK completely abrogated IL-1alpha inhibition of Dex-induced GRE-CAT
      activity. Taken together, these results demonstrate that activation of p38 MAPK
      pathways are involved in IL-1alpha-mediated inhibition of GR function. In
      addition, these findings extend the intracellular targets of p38 to include the
      GR and indicate that p38 inhibitors may have special utility in immunologic
      and/or neuropsychiatric disorders associated with impaired GR-mediated feedback
      inhibition.

PMID- 14699443
TI  - Intestinal permeability is decreased in anorexia nervosa.
AB  - Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal
      tract affect intestinal permeability (IP) leading to an increased penetration of
      substances that passively cross intestinal epithelium via intercellular pathways.
      We hypothesised that an increase in IP could occur in patients with anorexia
      nervosa because of their prolonged fasting and chronic malnutrition. Therefore,
      we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched
      healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose,
      after an overnight fast, subjects ingested an oral solution containing 5 g
      lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected
      immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of
      the sugar solution. Urinary lactulose and mannitol were determined by high
      performance anion exchange chromatography coupled with pulsed amperometric
      detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was
      significantly decreased in anorexic women because of a lower urinary recovery of
      lactulose. Moreover, in patients, the time course of lactulose excretion
      significantly differs from healthy controls. These results do not confirm our
      hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo
      functional status of intestinal mucosa, the present findings support the idea
      that changes in the anatomo-physiology of intestinal mucosa occur in anorexia
      nervosa.

PMID- 14699444
TI  - A genome-wide screen for genes influencing conduct disorder.
AB  - While behavioral genetic studies have suggested that childhood conduct disorder
      is under genetic influence, studies aimed at gene identification are lacking.
      This study represents the first genome-wide linkage analysis directed toward
      identifying genes contributing to conduct disorder. Genome screens of
      retrospectively reported childhood conduct disorder and conduct disorder
      symptomatology were carried out in the genetically informative adult sample
      collected as part of the Collaborative Study on the Genetics of Alcoholism
      (COGA). The results suggest that regions on chromosomes 19 and 2 may contain
      genes conferring risk to conduct disorder. Interestingly, the same region on
      chromosome 2 has also been linked to alcohol dependence in this sample. Childhood
      conduct disorder is known to be associated with the susceptibility for future
      alcohol problems. Taken together, these findings suggest that some of the genes
      contributing to alcohol dependence in adulthood may also contribute to conduct
      disorder in childhood.

PMID- 14699445
TI  - Findings in an independent sample support an association between bipolar
      affective disorder and the G72/G30 locus on chromosome 13q33.
AB  - Markers near the nested genes G72 and G30 on chromosome 13q33 have been
      implicated in the etiology of schizophrenia and, recently, bipolar affective
      disorder (BPAD). Hattori et al (2003) reported that single-nucleotide
      polymorphisms (SNPs) near the G72/G30 locus were associated with BPAD in a sample
      of 22 pedigrees, and that SNP haplotypes were associated in a second, larger
      sample of triads. The present study attempts to replicate this finding in an
      independent case-control sample. Six SNPs near the G72/G30 locus, including the
      most strongly associated markers in the previous study, were tested in 139 cases
      and 113 ethnically matched controls. Significant association was detected between
      BPAD and two adjacent SNPs (smallest P=0.007; global P=0.024). Haplotype analysis
      produced additional support for association (smallest P=0.004; global P=0.004).
      Analysis of 31 unlinked microsatellite markers detected no population
      stratification in the cases or controls studied. Although the associated alleles
      and haplotypes differ from those previously reported, these new results provide
      further evidence, in an independent sample, for an association between BPAD and
      genetic variation in the vicinity of the genes G72 and G30.

PMID- 14699446
TI  - Possible evidence for a common risk locus for bipolar affective disorder and
      schizophrenia on chromosome 4p16 in patients from the Faroe Islands.
AB  - Patients with schizophrenia (n=11) and bipolar affective disorder (n=17) from the
      relatively isolated population of the Faroe Islands were genotyped for 34
      polymorphic markers on chromosome 4 in a search for allelic association and
      haplotype sharing among distantly related patients. When considering bipolar
      patients only, there was no clearcut support for any region on chromosome 4. The
      two-marker segment D4S394-D4S2983 at 4p16.1 was, however, supported by a P-value
      of 0.0162. For patients with schizophrenia, there was reasonable support for
      4p16.1 as marker D4S2281 (P=0.0019), a two-marker segment (D4S2281-D4S1605,
      P=0.0009) and a three-marker segment (D4S2923-D4S2928-D4S1582, P-0.0005) appeared
      to be associated with schizophrenia, with some alleles/haplotypes occurring with
      different frequencies in patients compared to controls. When combining both
      psychiatric disorders, chromosome 4p16.1 received further support from five
      partially overlapping two- and three-marker segments (D4S394-D4S2983, P=0.0039;
      D4S2281-D4S1605, P=0.0027 and D4S394-D4S2983-D4S2923, P=0.006; D4S2923-D4S2928
      D4S1582, P=0.00007; D4S1582-D4S1599-D4S2281, P=0.005). Increased haplotype
      sharing in patients with schizophrenia and in the combined data set was partly
      supported by Fisher's exact test and tests based on the genealogy. Our study
      yields support for a common risk gene for schizophrenia and bipolar affective
      disorder on the short arm of chromosome 4, as suggested by previous findings in
      the neighbouring Scottish population.

PMID- 14699447
TI  - A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association
      with stress response and aggression.
AB  - Variations in the human mu-opioid receptor gene have driven exploration of their
      biochemical, physiological and pathological relevance. We investigated the
      existence of variations in the nonhuman primate mu-opioid receptor gene to
      determine whether nonhuman primates can model genotype/phenotype associations of
      relevance to humans. Similar to the A118G single nucleotide polymorphism (SNP) in
      the human mu-opioid receptor gene, a SNP discovered in the rhesus monkey mu
      opioid receptor gene (C77G) alters an amino acid in the N-terminal arm of the
      receptor (arginine for proline at position 26). Two mu-opioid receptor coding
      regions isolated from a single heterozygous (C77/G77) rhesus monkey brain were
      expressed in HEK-293 cells and characterized in radioreceptor assays. Paralleling
      the findings of increased affinity of beta-endorphin by the A118G allele in the
      human, the rhesus monkey mu-opioid receptor protein derived from the G77
      containing clone demonstrated a 3.5-fold greater affinity for beta-endorphin than
      the receptor derived from the C77-containing clone. An assay developed to assess
      the incidence of the C77G SNP in a behaviorally and physiologically characterized
      cohort of rhesus monkeys (n=32) indicated that 44% were homozygous for C77
      containing alleles, 50% were heterozygous and 6% were homozygous for G77
      containing alleles. The presence of G77-containing alleles was associated with
      significantly lower basal and ACTH-stimulated plasma cortisol levels (P<0.03-0.05
      and P<0.02, respectively) and a significantly higher aggressive threat score
      (P<0.05) in vivo. In a cohort of 20 monkeys, a trend towards an inverse
      correlation between aggressive threat and plasma cortisol levels was observed.
      The findings suggest that mu-opioid receptor haplotypes in monkeys can contribute
      to individual variability in stress response and related aggression. The data
      support the use of nonhuman primates to investigate mu-opioid receptor
      genotype/phenotype relations of relevance to humans.

PMID- 14699448
TI  - The serotonin-2A receptor gene locus does not contain common polymorphism
      affecting mRNA levels in adult brain.
AB  - The serotonin-2A (HTR2A) receptor is a molecule of particular interest in
      biological psychiatry, as it is an important target for psychotropic drugs, and
      altered HTR2A expression has been found in several neuropsychiatric conditions,
      including depression and schizophrenia. Genetic association has been reported
      between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number
      of clinical phenotypes, including schizophrenia, clozapine response, psychotic
      symptoms in Alzheimer's disease and certain features of depression. Given that
      there are no known effects of the 102T/C polymorphism on the structure of the
      receptor, attention has switched to the possibility that the observations of both
      altered expression and genetic association point to functional sequence variants
      that alter expression of the HTR2A gene. Moreover, data have been presented
      recently suggesting that mRNAs containing the 102T- and C-alleles are
      differentially expressed. This suggests a direct effect of the variant itself on
      mRNA levels, or the influence of a distinct regulatory variant, such as the 
      1438A/G promoter polymorphism, with which it is in perfect linkage
      disequilibrium. The present study tested this hypothesis by employing a highly
      accurate quantitative allele- specific primer extension assay to measure the
      relative expression of brain mRNAs carrying each allele in 23 individuals
      heterozygous for the 102T/C polymorphism. Comparison between allele ratios
      derived from genomic DNA and mRNA from several cortical regions revealed that the
      102C- and T-alleles are expressed identically. Furthermore, the absence of any
      interindividual variability in relative mRNA allele ratio suggests that the HTR2A
      locus is unlikely to contain common polymorphisms or epigenetic modification that
      alter HTR2A mRNA levels in adult brain, and essentially exclude such phenomena as
      a potential explanation for the altered expression and genetic associations that
      have been reported to date.

PMID- 14699449
TI  - Guidelines for treatment of candidiasis.

PMID- 14699450
TI  - Outbreak of Shiga toxin-producing Escherichia coli O111:H8 infections among
      attendees of a high school cheerleading camp.
AB  - Few US clinical laboratories screen stool specimens for Shiga toxin-producing
      Escherichia coli (STEC) other than E. coli O157. An outbreak of STEC O111:H8
      infections indistinguishable from E. coli O157:H7 at a youth camp highlights the
      need to improve non-O157 STEC surveillance. Interviews of 521 (80%) of 650
      attendees revealed 55 (11%) were ill; 2 developed hemolytic-uremic syndrome.
      Illness was associated with consuming salad during the camp's first lunch meal
      (hazard ratio [HR], 4.68; P<.01), consuming ice provided in barrels on the camp's
      final day (HR, 3.41; P<.01), eating cob corn (HR, 3.22; P<.01), and eating a
      dinner roll (HR, 2.82; P<.01). Cultures of 2 of 11 stools yielded E. coli
      O111:H8. Results of serologic testing and additional stool cultures demonstrated
      no evidence of infection with other bacterial pathogens, including E. coli O157,
      and supported infection with E. coli O111. Clinical laboratories should routinely
      screen suspect specimens for non-O157 STEC and should serotype and report Shiga
      positive isolates.

PMID- 14699451
TI  - Identification of risk factors for extrapulmonary tuberculosis.
AB  - The proportion of extrapulmonary tuberculosis cases in the United States has
      increased from 16% of tuberculosis cases, in 1991, to 20%, in 2001. To determine
      associations between the demographic, clinical, and life style characteristics of
      patients with tuberculosis and the occurrence of extrapulmonary tuberculosis, a
      retrospective case-control study was conducted. This study included 705 patients
      with tuberculosis, representing 98% of the culture-proven cases of tuberculosis
      in Arkansas from 1 January 1996 through 31 December 2000. A comparison between 85
      patients with extrapulmonary tuberculosis (case patients) and 620 patients with
      pulmonary tuberculosis (control patients) showed women (OR, 1.98; 95% CI, 1.25
      3.13), non-Hispanic blacks (OR, 2.38; 95% CI, 1.42-3.97), and HIV-positive
      persons (OR, 4.93; 95% CI, 1.95-12.46) to have a significantly higher risk for
      extrapulmonary tuberculosis than men, non-Hispanic whites, and HIV-negative
      persons. This study expands the knowledge base regarding the epidemiology of
      extrapulmonary tuberculosis and enhances our understanding of the relative
      contribution of host-related factors to the pathogenesis of tuberculosis.

PMID- 14699452
TI  - Primary central nervous system phaeohyphomycosis: a review of 101 cases.
AB  - Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These
      fungi rarely cause life-threatening disease. We reviewed 101 cases of culture
      proven primary central nervous system phaeohyphomycosis reported in the English
      language literature from 1966 to 2002. The most frequently isolated species was
      Cladophialophora bantiana. The next most frequent isolate was Ramichloridium
      mackenziei, seen exclusively in patients from the Middle East. More than one-half
      of the cases occurred in patients with no known underlying immunodeficiency.
      Mortality rates were high regardless of immune status. Therapy is not
      standardized, although the combination of amphotericin B, flucytosine, and
      itraconazole may improve survival rates. Newer azoles, such as voriconazole, also
      have a broad spectrum of activity against these fungi, although clinical
      experience is limited. Complete excision of brain lesions may provide better
      results than simple aspiration. An aggressive medical and surgical approach is
      warranted in treating these infections to optimize outcomes.

PMID- 14699453
TI  - Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis in
      India.
AB  - Miltefosine has previously been shown to cure 97% of cases of visceral
      leishmaniasis (VL) in Indian adults. Because approximately one-half of cases of
      VL occur in children, we evaluated use of the adult dosage of miltefosin (2.5
      mg/kg per day for 28 days) in 80 Indian children (age, 2-11 years) with
      parasitologically confirmed infection in an open-label clinical trial. Clinical
      and parasitological parameters were reassessed at the end of treatment and 6
      months later. One patient died of intercurrent pneumonia on day 6. The other 79
      patients demonstrated no parasites after treatment, had marked clinical
      improvement, and were deemed initially cured. Three patients had relapse, and 1
      patient was lost to follow-up. The final cure rate was 94% for all enrolled
      patients and 95% for evaluable patients. Side effects included mild-to-moderate
      vomiting or diarrhea (each in approximately 25% of patients) and mild-to
      moderate, transient elevations in the aspartate aminotransferase level during the
      early treatment phase (in 55%). This trial indicates that miltefosine is as
      effective and well tolerated in Indian children with VL as in adults and that it
      can be recommended as the first choice for treatment of childhood VL in India.

PMID- 14699454
TI  - Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of
      pneumococcal pneumonia.
AB  - We evaluated the usefulness of a rapid urinary antigen test (Binax NOW; Binax) to
      detect Streptococcus pneumoniae for the early diagnosis of community-acquired
      pneumococcal pneumonia (PP) in 220 nonseverely immunosuppressed adults. We
      compared results of this test with those of sputum Gram staining. The rapid
      urinary antigen test showed limited sensitivity (65.9%; 95% confidence interval
      [CI], 51.4-80.4) but high specificity (100%; 95% CI, 99.7-100) for diagnosing PP.
      The test was more sensitive for patients with versus those without high-risk
      pneumonia (94% vs. 63%; P<.001) and for patients without versus those with
      demonstrative results of a sputum Gram stain (97% vs. 55%; P<.001), and it tended
      to be more sensitive for patients with versus those without bacteremic PP (92%
      vs. 74%; P=NS). Rapid urinary antigen testing permitted early diagnosis of PP in
      26% more patients than did Gram staining but missed 22% of the rapid diagnoses
      initially identified by Gram staining. On the basis of our results, a sequential
      approach is proposed, with reservation of urinary antigen testing for high-risk
      patients for whom demonstrative results of a sputum Gram stain are unavailable.

PMID- 14699455
TI  - Acute community-acquired bacterial sinusitis: the value of antimicrobial
      treatment and the natural history.
AB  - Two areas of investigation were reviewed: (1) placebo-controlled trials of
      antimicrobial treatment involving patients with a clinical diagnosis of acute
      community-acquired bacterial sinusitis (ACABS) for whom pre- and posttherapy
      sinus aspirate cultures were not performed, and (2) uncontrolled trials of
      antimicrobial treatment involving patients with ACABS for whom pre- and
      posttherapy sinus aspirate cultures were performed. The clinical diagnostic
      criteria in the controlled trials were not correlated with sinus aspirate culture
      results and, thus, were of questionable validity. Most of the populations
      probably included patients with viral rhinosinusitis. In 10 uncontrolled studies,
      the posttreatment, weighted, pooled mean bacterial resolution rate (+/- standard
      error) at 7-10 days, based on sinus aspirate culture results, was 91%+/-10%. In 9
      controlled trials, the weighted pooled mean rate of clinical improvement (+/-
      standard deviation) at 7-14 days for placebo recipients was 52%+/-18%. In 1
      controlled trial in which diagnosis was based on duration of unimproved illness,
      57% of placebo recipients and 85.5% of treated patients were healthy or had
      improved by day 10. Additional studies of ACABS are needed.

PMID- 14699456
TI  - Association of clinical signs and symptoms with bacterial findings in acute
      otitis media.
AB  - In acute otitis media (AOM), a means of prediction of the bacterial pathogen
      based on symptoms and signs would be valuable in selecting appropriate
      antimicrobial treatment. Children in the control arm (n=831) in the Finnish
      Otitis Media Vaccine Trial were prospectively observed in a study clinic setting
      from the age of 2 to 24 months. In patients with AOM, myringotomy with aspiration
      was performed, and middle ear fluid samples were cultured for bacterial
      pathogens. Symptoms and signs of respiratory infections were thoroughly recorded.
      Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were
      the most common bacterial pathogens. Pneumococcal AOM was associated with more
      severe AOM characterized by fever and earache. AOM due to H. influenzae was
      associated with eye symptoms and findings. Accurate prediction of a bacterial
      cause of infection based on symptoms and signs of AOM was not possible, but a
      specific cause was predicted in some situations, with a high probability of
      applicability to clinical practice.

PMID- 14699457
TI  - Bacteremia due to Klebsiella pneumoniae isolates producing the TEM-52 extended
      spectrum beta-lactamase: treatment outcome of patients receiving imipenem or
      ciprofloxacin.
AB  - The treatment outcome of 35 cases of bacteremia due to Klebsiella pneumoniae
      isolates producing TEM-52 extended-spectrum beta-lactamase was studied. Twenty
      eight cases, classified as "nonfatal disease" using the McCabe and Jackson
      classification, were investigated with regard to ciprofloxacin and imipenem
      response. Because ciprofloxacin was active in vitro against 21 of 28 isolates,
      only the treatment outcome of the ciprofloxacin-susceptible subgroup was
      evaluated. Eight of 10 cases occurred in patients who experienced a complete
      response to imipenem; 2 of 10 failed to respond. In contrast, only 2 of 7 cases
      had a partial response to ciprofloxacin, and, in 5 of 7 cases, the treatment
      failed. Statistical analysis revealed a significant difference in the treatment
      outcome of the 2 groups (P=.03). Because the isolates had minimum inhibitory
      concentrations of ciprofloxacin close to the susceptibility breakpoint, treatment
      failure could be ascribed to the inability of the drug to reach therapeutic
      concentrations at infected sites.

PMID- 14699458
TI  - A review of natural-rubber latex allergy in health care workers.
AB  - This brief review of natural-rubber latex (NRL) allergy in health care workers
      (HCWs) includes the definition of NRL allergy and data on its epidemiology,
      pathogenesis, diagnostic algorithm, management, long-term outcomes, economic
      impact, cost-effectiveness of changing facilities to a latex-free environment,
      and prevention. The data presented suggest that an individual with type I or type
      IV hypersensitivity to NRL should be able to continue to work in the workplace
      with careful evaluation and reasonable accommodations. Reducing exposure to latex
      is a safe and more economical alternative to complete removal of the individual
      from the place of employment. The use of low-allergen, nonpowdered NRL gloves
      substantially reduces airborne exposure to latex in most health care settings.

PMID- 14699459
TI  - Use of total lymphocyte count for monitoring response to antiretroviral therapy.
AB  - The CD4 cell count has become a key laboratory measurement in the management of
      human immunodeficiency virus (HIV) disease. In ideal situations, HIV-infected
      persons are followed up longitudinally with serial CD4 cell counts to determine
      disease progression, risk for opportunistic infection, and the need for
      prophylactic or therapeutic intervention. However, the use of the CD4 cell count
      in resource-limited settings is often not possible because of lack of
      availability and high cost. Thus, other laboratory markers have been proposed as
      substitutes for the CD4 cell count. The data regarding the clinical utility of
      the total lymphocyte count (TLC) as a potential surrogate marker of immune
      function in patients with HIV disease are examined. The role of the TLC in the
      initiation of antiretroviral therapy and opportunistic infection prophylaxis, as
      well as the role of the TLC in monitoring the response to antiretroviral therapy,
      are also addressed.

PMID- 14699460
TI  - Improvement in lipoatrophy associated with highly active antiretroviral therapy
      in human immunodeficiency virus-infected patients switched from stavudine to
      abacavir or zidovudine: the results of the TARHEEL study.
AB  - Stavudine use is a contributing factor for lipoatrophy, whereas use of abacavir
      or zidovudine is less likely to cause this complication. The TARHEEL study was a
      48-week, open-label study that assessed changes in lipoatrophy after abacavir (86
      patients [73%]) or zidovudine (32 patients [27%]), 300 mg twice daily, was
      substituted for stavudine for 118 human immunodeficiency virus (HIV)-infected
      patients (HIV type 1 RNA level, <400 copies/mL) with virological suppression who
      had developed lipoatrophy after > or =6 months of stavudine-based treatment. At
      week 48, full-body dual-energy x-ray absorptiometry demonstrated a median
      increase in arm fat of 35%, leg fat of 12%, and trunk fat of 18%, compared with
      the baseline level. These improvements coincided with fat gain in lipoatrophic
      areas that was documented by computerized tomography. Results of a "body image"
      questionnaire showed that a substantial percentage of patients reported some or a
      lot of fat gain in the arms (22%), legs (18%), buttocks (19%), and face (27%).
      HIV suppression was maintained over the study period. In conclusion, replacing
      stavudine with abacavir or zidovudine resulted in improvement in stavudine
      induced lipoatrophy.

PMID- 14699461
TI  - Clinical stability in human immunodeficiency virus-infected patients with
      community-acquired pneumonia.
AB  - Clinical stability (CS), defined as normalization of vital signs, is often used
      to manage inpatients with community-acquired pneumonia (CAP). The main objective
      of our study was to identify a reliable definition of CS for human
      immunodeficiency virus (HIV)-positive patients with CAP. During an 18-month
      period, 437 HIV-positive Italian inpatients with CAP were enrolled in the study.
      We used 3 definitions of CS (from a less conservative [definition 1] to a more
      conservative [definition 3] definition) based on combinations of different
      thresholds for vital signs. Assessments were performed at admission and daily
      during the hospital stay. For the 3 definitions, 14.9%, 8.0%, and 4.8% of
      patients were stable at baseline, with deterioration after reaching CS in 7.16%,
      4.76%, and 2.05%, respectively. The 8 patients whose conditions deteriorated
      after reaching CS definition 3 (systolic blood pressure, >90 mm Hg; pulse, <90
      beats/min; respiratory rate, <20 breaths/min; oxygen saturation, >90%;
      temperature, <37 degrees C; ability to eat; and normal mental status) survived
      and were discharged from the hospital. The more conservative definition of CS
      appears to be reliable for the management of HIV-infected patients with CAP.

PMID- 14699462
TI  - Malabsorption of rifampin and isoniazid in HIV-infected patients with and without
      tuberculosis.
AB  - The absorption of rifampin, isoniazid, and D-xylose in patients with human
      immunodeficiency virus (HIV) infection and diarrhea, in patients with HIV
      infection and tuberculosis (TB), in patients with pulmonary TB alone, and in
      healthy subjects was studied. Percentage of dose of the drugs, their metabolites,
      and D-xylose excreted in urine were calculated. A significant reduction in the
      absorption of drugs and D-xylose in both the HIV infection/diarrhea and HIV
      infection/TB groups was observed (P<.05), and the correlation between them was
      significant. Our results indicate that patients with HIV infection and diarrhea
      and those with HIV infection and TB have malabsorption of rifampin and isoniazid.

PMID- 14699463
TI  - Adequacy of early empiric antibiotic treatment and survival in severe sepsis:
      experience from the MONARCS trial.
AB  - As part of the Monoclonal Anti-TNF: A Randomized Controlled Sepsis (MONARCS)
      trial, which enrolled patients with suspected sepsis, we sought to determine
      whether adequate antibiotic therapy was associated with a decreased mortality
      rate. The study enrolled 2634 patients, 91% of whom received adequate antibiotic
      therapy. The mortality rate among patients given adequate antibiotic treatment
      was 33%, versus 43% among patients given inadequate treatment (P<.001). We
      conclude that adequate antibiotic therapy results in a significant decrease in
      the crude mortality rate among patients suspected of sepsis.

PMID- 14699464
TI  - Severe West Nile virus disease in healthy adults.
AB  - The inpatient records of 44 case patients with West Nile virus infection
      hospitalized in 2002 were reviewed. Sixty-five percent of the case patients had
      encephalitis, and 35% had aseptic meningitis. There was no significant difference
      in the distribution of aseptic meningitis versus encephalitis among adults aged <
      or =50 years compared with adults aged > or =65 years. Focal weakness, likely due
      to anterior horn cell involvement, was present in 10 case patients (overall rate,
      23%; rate among patients with encephalitis, 34%). Case patients with focal
      weakness who were aged < or =50 years had monoparesis, whereas those aged > or
      =65 years had paraparesis or quadriparesis. The overall mortality rate was 14%,
      and the mortality rate in patients aged > or =65 years was 35%. Increased age was
      associated with an increased mortality rate. The presence of paraparesis or
      quadriparesis was not independently predictive of mortality.

PMID- 14699465
TI  - Sensitive and quantitative detection of severe acute respiratory syndrome
      coronavirus infection by real-time nested polymerase chain reaction.
AB  - A quantitative, real-time, nested polymerase chain reaction (PCR) method,
      combining the high sensitivity of nested PCR with time-saving real-time
      instrumentation, was developed for large-scale screening for severe acute
      coronavirus (SARS) coronavirus. Forty-six clinical specimens were analyzed by
      this method, and results were compared with those obtained by conventional,
      single-round, real-time reverse-transcriptase PCR (RT-PCR) performed in parallel.
      Of the 17 positive results, 2 identified by our method were not detected by
      single-round, real-time RT-PCR, which suggests that real-time nested PCR has the
      potential for increased sensitivity, leading to earlier detection of SARS.

PMID- 14699466
TI  - Crouching tiger, hidden dragon: the laboratory diagnosis of severe acute
      respiratory syndrome.

PMID- 14699467
TI  - Etiology of clinical proctitis among men who have sex with men.
AB  - In this retrospective review of cases of clinical proctitis, we identified the
      frequency of common sexually transmitted diseases (STDs) among men who have sex
      with men on the basis of reports from the municipal STD clinic in San Francisco.
      Of note, gonorrhea and chlamydia were the most common STDs, followed by herpes
      and syphilis. Current STD treatment guidelines recommend empiric treatment for
      gonorrhea and chlamydia, but treatment for herpes should also be considered. The
      implications for human immunodeficiency virus (HIV) transmission are also
      discussed.

PMID- 14699468
TI  - Continuous infusion of amphotericin B deoxycholate: a cost-effective gold
      standard for therapy of invasive fungal infections?

PMID- 14699469
TI  - Reduction of nephrotoxicity associated with amphotericin B deoxycholate.

PMID- 14699470
TI  - Amphotericin B: is a lipid-formulation gold standard feasible?

PMID- 14699471
TI  - Lipid amphotericin B formulations as comparators in clinical trials.

PMID- 14699475
TI  - Gastroenterology in the Netherlands.

PMID- 14699480
TI  - The national obesity crisis: a call for action.

PMID- 14699481
TI  - Image of the month.

PMID- 14699482
TI  - Pressure activates colon cancer cell adhesion by inside-out focal adhesion
      complex and actin cytoskeletal signaling.
AB  - BACKGROUND AND AIMS: Few circulating tumor cells implant or cause metastasis. We
      hypothesized that venous or lymphatic pressure or iatrogenic pressure during
      resection activates signals governing malignant colonocyte adhesion. METHODS: We
      studied the effect of 15 mm Hg increased pressure for 30 minutes on adhesion of
      primary human colon cancer cells and SW620 colonocytes to collagen and
      endothelial cells. We modulated integrin affinity with extracellular cations. We
      assessed binding affinity by detachment assay; integrin surface expression by
      flow cytometry; and focal adhesion kinase (FAK), Src, and extracellular signal
      regulated kinase (ERK) activation by Western analysis and Src in vitro kinase
      assay. We inhibited Src (PP2), FAK (small RNA interference, SiRNA, or FRNK
      transfection), MEK (PD98059), PKC (calphostin C), and actin destabilization
      (phalloidin). RESULTS: Pressure and manganese stimulated primary and SW620
      colonocyte adhesion to collagen. Pressure also stimulated SW620 adhesion to
      endothelial monolayers. Pressure strengthened SW620 binding force to matrix
      without changing integrin surface expression. Pressure activated SW620 FAK and
      Src, but not ERK. Manganese did not. Calcium-inhibited adhesion but stimulated
      FAK (but not Src). PP2 prevented pressure activation of Src, Src phosphorylation
      of FAK576, and pressure-stimulated adhesion but not FAK397 autophosphorylation.
      FRNK transfection or FAK SiRNA also prevented pressure-stimulated adhesion. FAK
      SiRNA ablated pressure-activated FAK397, Src, and FAK576 phosphorylation. Neither
      Src nor FAK inhibition blocked cation effects. Phalloidin prevented pressure
      stimulated adhesion. PD98059 or calphostin C did not. CONCLUSIONS: In contrast to
      divalent cations, extracellular pressure may increase integrin affinity and
      promote colon cancer adhesion via actin dependent inside-out FAK and Src signals.
      This mechanotransduced pathway may regulate metastasizing tumor cell adhesion.

PMID- 14699483
TI  - The safety profile of infliximab in patients with Crohn's disease: the Mayo
      clinic experience in 500 patients.
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate the short- and long
      term safety of infliximab in patients with Crohn's disease in clinical practice.
      METHODS: The medical records of 500 consecutive patients treated with infliximab
      at the Mayo Clinic were reviewed and abstracted for demographic features and
      adverse events. The likelihood of a causal relationship to infliximab for each
      adverse event was determined by calculating an intrinsic likelihood
      (imputability) score. RESULTS: The 500 patients received a median of 3 infusions
      and had a median follow-up of 17 months. Forty-three patients (8.6%) experienced
      a serious adverse event, of which 30 (6%) were related to infliximab. Acute
      infusion reactions occurred in 19 of 500 patients (3.8%). Serum sickness-like
      disease occurred in 19 of 500 patients and was attributed to infliximab in 14
      (2.8%). Three patients developed drug-induced lupus. One patient developed a new
      demyelination disorder. Forty-eight patients had an infectious event, of which 41
      (8.2%) were attributed to infliximab. Twenty patients had a serious infection: 2
      had fatal sepsis, 8 had pneumonia (of which 2 cases were fatal), 6 had viral
      infections, 2 had abdominal abscesses requiring surgery, one had arm cellulitis,
      and one had histoplasmosis. Nine patients had a malignant disorder, 3 of which
      were possibly related to infliximab. A total of 10 deaths were observed. For 5 of
      these patients (1%), the events leading to death were possibly related to
      infliximab. CONCLUSIONS: Short- and long-term infliximab therapy is generally
      well tolerated. However, clinicians must be vigilant for the occurrence of
      infrequent but serious events, including serum sickness-like reaction,
      opportunistic infection and sepsis, and autoimmune disorders.

PMID- 14699484
TI  - The DeltaF508 mutation results in loss of CFTR function and mature protein in
      native human colon.
AB  - BACKGROUND AND AIMS: Deletion of the codon for phenylalanine at position 508
      (DeltaF508) is the most frequent disease-causing mutation in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. In heterologous cells, defective
      processing of the DeltaF508 protein results in endoplasmic reticulum retention,
      proteolytic degradation, and absence of adenosine 3',5'-cyclic monophosphate
      (cAMP)-dependent plasma membrane Cl(-) conductance. However, data with respect to
      the processing block of DeltaF508 protein in native epithelia are limited and
      conflicting. METHODS: To characterize both the fate and function of DeltaF508
      protein in a native epithelium, we measured CFTR-mediated Cl(-) secretion,
      localization of the CFTR protein, and CFTR maturation in rectal biopsy specimens
      from normal individuals and DeltaF508 homozygous patients with cystic fibrosis
      (CF). RESULTS: Ussing chamber studies showed that cAMP-dependent and cholinergic
      Cl(-) secretion was absent from rectal tissues freshly excised from DeltaF508
      homozygous patients with CF. By immunohistochemistry, we detected wild-type but
      not DeltaF508 CFTR at the luminal membrane of crypt colonocytes. By sequential
      immunoprecipitation and immunoblotting analyses, mature CFTR protein was detected
      in normal but not in DeltaF508 homozygous tissues. CONCLUSIONS: Collectively,
      these data show that there is insufficient maturation and transport of DeltaF508
      CFTR from the endoplasmic reticulum to the apical membrane to support CFTR
      mediated Cl(-) secretion in the CF colon.

PMID- 14699485
TI  - The role of mismatch repair gene defects in the development of adenomas in
      patients with HNPCC.
AB  - BACKGROUND AND AIMS: The adenoma-carcinoma sequence in hereditary nonpolyposis
      colorectal cancer (HNPCC) is accelerated. It remains unknown whether the mismatch
      repair (MMR) defect also promotes the development of adenomas. The aim of this
      study was to compare the risk of developing colorectal adenoma and carcinoma in
      HNPCC carriers and noncarriers (controls) and to compare the features of adenomas
      in both groups. METHODS: Eighty-six families with a known MMR gene mutation from
      the Dutch HNPCC Registry were analyzed. Subjects with known mutation status with
      colonoscopies performed for the purpose of surveillance were selected for this
      study. Information on the surveillance examinations was obtained from medical
      reports. The histology of all adenomas was confirmed. Immunohistochemistry was
      performed in a subgroup of adenomas. RESULTS: We identified 249 carriers and 247
      controls. The proportion of subjects free of an adenoma at the age of 60 years
      was 29.7% for carriers and 70.8% for controls (P < 0.05). The adenomas in
      carriers were larger, and a higher proportion had villous components and/or high
      grade dysplasia (P < 0.05, all analyses). The adenomas and carcinomas of the
      carriers were located predominantly in the proximal colon. Most adenomas showed
      absent staining of the MMR proteins. CONCLUSIONS: This study indicates that the
      MMR defect is involved in the early stages of development of adenomas. We
      recommend immunohistochemical staining of large adenomas with high-grade
      dysplasia in young patients (younger than 50 years) to identify patients with
      suspected HNPCC.

PMID- 14699486
TI  - Mechanoreceptors of the proximal stomach: Role in triggering transient lower
      esophageal sphincter relaxation.
AB  - BACKGROUND AND AIMS: The role of fundic tension and stretch mechanoreceptors in
      triggering transient lower esophageal sphincter (LES) relaxation is still
      unknown. This information would be useful for the development of effective
      pharmacologic strategies. To elucidate this topic, gastric contractile activity
      was modified during isovolumetric gastric distention at 2 different volumes.
      METHODS: LES (Dentsleeve) and gastric (barostat) motility were recorded in 21
      healthy subjects during studies comprising two 30-minute isovolumetric gastric
      distentions (placebo and glucagon or erythromycin). Glucagon (bolus of 4.8
      microg/kg plus infusion of 9.6 microg x kg(-1) x h(-1)) was administered at high
      intragastric volume (i.e., 75% of the threshold volume for discomfort; n = 7) and
      erythromycin (3 mg/kg) at high (n = 7) and low intragastric volume (i.e., at
      perception threshold; n = 7). RESULTS: Glucagon decreased (P < 0.05) baseline
      intragastric pressure and abolished gastric contractions (0 vs. 16.7 +/- 2.3),
      whereas erythromycin increased (P < 0.05) baseline pressure and doubled (P <
      0.05) the rate of gastric contractions at both volumes. Neither drug affected the
      rate of transient LES relaxations. Low intragastric volume induced a lower rate
      of transient LES relaxations (1.7 +/- 0.3 vs. 5.7 +/- 1.1; P < 0.01) and gastric
      contractions (11.8 +/- 2.5 vs. 20.5 +/- 3.1; P < 0.05) compared with high volume
      but similar baseline intragastric pressure (10.6 +/- 0.6 vs. 11.9 +/- 0.9 mm Hg).
      CONCLUSIONS: Stretch receptors (gastric volume) seem to be more relevant than
      tension receptors in triggering transient LES relaxation.

PMID- 14699487
TI  - Finney of the Finney pyloroplasty.

PMID- 14699488
TI  - Predictive value of the balloon expulsion test for excluding the diagnosis of
      pelvic floor dyssynergia in constipation.
AB  - BACKGROUND AND AIMS: The aim of this study was to establish a simple method to
      exclude the possibility of pelvic floor dyssynergia (PFD) in constipated patients
      and thus avoid unnecessary expensive physiologic studies. METHODS: Patients with
      suspicion of functional constipation (FC) were studied prospectively between 1994
      and 2002, excluding those with severe systemic, psychological, or symptomatic
      anorectal/colonic disorders or taking medications that might modify symptoms or
      results of studies. Diagnosis of PFD was established retrospectively by
      manometric plus defecographic findings according to Rome II criteria. Two groups
      of patients were identified: FC without PFD (FC group) and PFD group. A 30-day
      symptom diary and balloon expulsion test results were evaluated in all patients.
      Clinical differences and results of the expulsion test were statistically
      compared between groups. RESULTS: Of 359 patients evaluated, 130 were included
      (FC group, 106; PFD group, 24). According to data from the diary, only anal pain
      was more frequent in the PFD group compared with the FC group (anal pain in >25%
      of defecations, 70.8% vs. 40.6%; P < 0.05, chi(2) test). The expulsion test was
      pathologic in 21 of 24 patients with PFD and 12 of 106 without PFD. The
      specificity and negative predictive value of the test for excluding PFD were 89%
      and 97%, respectively. CONCLUSIONS: The balloon expulsion test is a simple and
      useful screening procedure to identify constipated patients who do not have PFD.
      Symptoms are not enough to differentiate between subtypes of constipation.

PMID- 14699489
TI  - CD40-mediated immune-nonimmune cell interactions induce mucosal fibroblast
      chemokines leading to T-cell transmigration.
AB  - BACKGROUND AND AIMS: The CD40 pathway is a key mediator of inflammation and
      autoimmunity. We investigated cell adhesion molecule (CAM) up-regulation and
      chemokine production by CD40-positive human intestinal fibroblasts (HIF) and
      microvascular endothelial cells (HIMEC) induced by CD40 ligand (CD40L)-positive T
      cells and soluble CD40L and their effect on T-cell adhesion and transmigration.
      METHODS: Expression of CD40, CD40L, and CAM was assessed by immunohistochemistry,
      confocal microscopy and flow cytometric analysis, and chemokine production using
      enzyme-linked immunosorbent assay. Calcein-labeled T cells were used to assay HIF
      adhesion and Transwell HIMEC transmigration. RESULTS: Ligation of CD40-positive
      HIF and HIMEC by CD40L-positive T cells or soluble CD40L induced up-regulation of
      CAM expression as well as interleukin-8 and RANTES production. The specificity of
      these responses was shown by inhibition with a CD40L blocking antibody and by
      CD40 signaling-dependent p38 mitogen-activated protein kinase phosphorylation. On
      CD40 ligation, HIF increased their T-cell binding capacity and generated
      chemoattractants able to induce T-cell migration through HIMEC monolayers.
      CONCLUSIONS: Activation of the CD40/CD40L system in the gut mucosa may trigger a
      self-sustaining loop of immune-nonimmune cell interactions leading to an antigen
      independent influx of T cells that contributes to chronic inflammation.

PMID- 14699490
TI  - Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD
      mutant hepatitis B virus.
AB  - BACKGROUND AND AIMS: Prolonged lamivudine therapy is associated with treatment
      resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and
      safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic
      hepatitis B (CHB) and YMDD mutant HBV. METHODS: Ninety-five patients with
      compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or
      placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty
      patients with decompensated hepatitis B or post-liver transplantation (group B)
      received adefovir and lamivudine. The primary end point was a decline in serum
      HBV DNA level to 10(5) copies/mL or a >2 log(10) reduction from baseline at weeks
      48 and 52. RESULTS: HBV DNA response occurred in 85% of patients (39 of 46) in
      group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P
      < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001)
      between treatment groups (median, -4.6 vs. +0.3 log(10) copies/mL, respectively).
      Normalization of alanine aminotransferase levels occurred in 31% of patients (14
      of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone
      (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA
      response (median change of -4.6 log(10) copies/mL) and improved liver chemistries
      (P < or = 0.001). Both treatment regimens were well tolerated, and renal function
      abnormalities were not observed in either group. CONCLUSIONS: The addition of
      adefovir dipivoxil to lamivudine in patients with CHB with compensated or
      decompensated liver disease due to YMDD mutant HBV is associated with virologic
      and biochemical improvement during 52 weeks of treatment and is well tolerated.

PMID- 14699491
TI  - Adefovir dipivoxil alone or in combination with lamivudine in patients with
      lamivudine-resistant chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Adefovir dipivoxil possesses potent in vitro and in vivo
      antiviral activity in wild-type hepatitis B. This study assessed the safety and
      efficacy of adefovir dipivoxil alone and in combination with lamivudine compared
      with ongoing lamivudine therapy in patients with chronic hepatitis B with
      compensated liver disease and lamivudine-resistant hepatitis B virus (HBV).
      METHODS: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with
      genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase
      (ALT) level > or =1.2 times the upper limit of normal, and serum HBV DNA level >
      or =6 log(10) copies/mL despite ongoing treatment with lamivudine were randomized
      to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil
      to ongoing lamivudine daily. The primary end point was the time-weighted average
      change from baseline in serum HBV DNA level (DAVG) up to week 16. RESULTS: Rapid
      reductions in serum HBV DNA level were seen by 4 weeks in all recipients of
      adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine group compared with 
      2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and
      adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change
      from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log(10)
      copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir
      dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of
      18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil,
      respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients
      receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving
      lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B
      surface antigen negative. CONCLUSIONS: These data, limited to patients with
      compensated liver disease, indicate that adefovir dipivoxil alone or in
      combination with ongoing lamivudine therapy provides effective antiviral therapy
      in patients with lamivudine-resistant HBV.

PMID- 14699492
TI  - Hepatitis B virus maintains its pro-oncogenic properties in the case of occult
      HBV infection.
AB  - BACKGROUND AND AIMS: Occult hepatitis B virus (HBV) infection is characterized by
      persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative
      individuals. The clinical relevance of this peculiar infection is still under
      debate. In particular, the impact of occult HBV infection in cases of
      hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and
      molecular status of occult HBV in patients with HCC. METHODS: We tested tumor
      tissues from 107 patients with HCC and the corresponding nontumor liver tissue
      from 72 of these patients for HBV DNA. We also examined liver specimens from 192
      patients with chronic hepatitis. All cases were hepatitis B surface antigen
      negative. Covalently closed circular HBV genomes, HBV transcripts, and viral
      integrated forms were investigated in cases of HCC found positive for occult HBV.
      RESULTS: Viral DNA was detected in 68 of 107 cases of HCC (63.5%) and in 63 of
      192 cases of chronic hepatitis (32.8%) (P < 0.0001; odds ratio, 3.6; 95%
      confidence interval, 2.2-5.9). The significant association of occult HBV with HCC
      was irrespective of age, sex, and contemporary hepatitis C virus infection. Both
      integrated viral DNA and covalently closed circular HBV genomes were detected in
      patients with occult HBV. Moreover, the presence of free HBV genomes was
      associated with persistence of viral transcription and replication. CONCLUSIONS:
      Our findings provide clear evidence that occult HBV is a risk factor for
      development of HCC and show that the potential mechanisms whereby overt HBV might
      induce tumor formation are mostly maintained in cases of occult infection.

PMID- 14699493
TI  - Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial
      cells in the colon.
AB  - BACKGROUND AND AIMS: The recent findings of bone morphogenetic protein (BMP)
      receptor Ia mutations in juvenile polyposis and frequent Smad4 mutations in colon
      cancer suggest a role for BMPs in the colonic epithelium and colon cancer. We
      investigated the role of BMP2 in the colon. METHODS: We assessed BMP receptor
      expression in cell lines using the reverse-transcribed polymerase chain reaction
      and immunoblotting. We investigated the effect of BMP2 on cell lines using the
      MTT assay and by immunoblotting for markers of differentiation, proliferation,
      and apoptosis. We assessed the expression of BMP2, its receptors, and signal
      transduction elements in mouse and human colon tissue using immunohistochemistry.
      We also investigated the effect of the BMP antagonist noggin in vivo in mice by
      assessing colon tissue with immunohistochemistry and immunoblotting. Finally, we
      investigated the expression of BMP2 in microadenomas from familial adenomatous
      polyposis patients. RESULTS: BMP receptors (BMPR) Ia, BMPR Ib, and BMPR II are
      all expressed in colonic epithelial cell lines. BMP2 inhibits colonic epithelial
      cell growth in vitro, promoting apoptosis and differentiation and inhibiting
      proliferation. BMP2, BMPRIa, BMPRIb, BMPRII, phosphorylated Smad1, and Smad4 are
      expressed predominantly in mature colonocytes at the epithelial surface in normal
      adult human and mouse colon. Noggin inhibits apoptosis and proliferation in mouse
      colonic epithelium in vivo. BMP2 expression is lost in the microadenomas of
      familial adenomatous polyposis patients. CONCLUSIONS: These data suggest that
      BMP2 acts as a tumor suppressor promoting apoptosis in mature colonic epithelial
      cells.

PMID- 14699494
TI  - Akt2, phosphatidylinositol 3-kinase, and PTEN are in lipid rafts of intestinal
      cells: role in absorption and differentiation.
AB  - BACKGROUND AND AIMS: In intestinal Na absorptive cells, phosphatidylinositol 3
      kinase (PI 3-K) is involved in rapid epidermal growth factor (EGF) stimulation of
      Na absorption by the brush border membrane (BBM) Na(+)/H(+) exchanger NHE3.
      However, how NHE3 is regulated by the PI 3-K pathway and the role of Akt2 are
      poorly defined. METHODS: The localization of Akt, PI 3-K, and NHE3 was determined
      by either immunocytochemistry and/or membrane fractionation using OptiPrep
      density gradient centrifugation. RESULTS: In ileum, active total Akt was present
      most in the villi and basal layer of the crypts, and Akt2 was mostly in villi. In
      villus cells, PI 3-K and Akt2 were mostly at the apical surface at which they
      were present partially in lipid rafts (LR). EGF increased PI 3-K and active Akt2
      in ileal BBM at the same time that it increased PI 3-K-dependent trafficking of
      NHE3 to BBM and stimulation of Na absorption. However, Akt2 was only active in
      the detergent soluble (DS) pool and not LR of ileal BBM, which correlated with
      the presence of PTEN in LR. In Caco-2 cells, while EGF stimulated BB NHE3, Akt2
      was active in both LR and DS pools. This correlated with the lack of PTEN in the
      LR of Caco-2 membranes. Akt2 also correlated with epithelial cell
      differentiation. Akt2 amount and activity were greater in differentiated than
      undifferentiated Caco-2 cells. CONCLUSIONS: These results suggest that LR may
      play an important role in determining the function of PI 3-K/Akt2 signaling,
      including stimulation of intestinal Na absorption. These results also suggest
      that LR-associated Akt2 may be involved in enterocyte differentiation.

PMID- 14699495
TI  - Cyclooxygenase-2 inhibitor (SC-236) suppresses activator protein-1 through c-Jun
      NH2-terminal kinase.
AB  - BACKGROUND AND AIMS: Aspirin exerts antitumor effect partly through blocking
      tumor promoter-induced activator protein-1 (AP-1) activation. The aim of this
      study is to determine how specific COX-2 inhibitor SC-236 mediates antitumor
      effect by modulation of AP-1-signaling pathway. METHODS: AP-1 transcriptional
      activity and DNA-binding activity were detected by luciferase reporter assay and
      gel shift assay, separately. Mitogen-activated protein kinase (MAPK) activation
      was determined by Western blot and in vitro kinase assay. Antisense
      oligonucleotide against c-Jun-N-terminal kinase (JNK) was used to suppress JNK
      expression. RESULTS: We showed that SC-236 inhibited 12-O-tetradecanoylphorbol-13
      acetate (PMA)-induced cell transformation in a dose-dependent manner in JB6
      cells. At a dose range (12.5-50 micromol/L) that inhibited cell transformation,
      SC-236 also inhibited anchorage-independent cell growth and AP-1-activation in 3
      gastric cancer cells, independent of COX-prostaglandin synthesis. SC-236 down
      regulated c-Jun-NH2-terminal kinase phosphorylation and activity. Suppression of
      JNK activity reversed the inhibitory effect on AP-1 activity by SC-236 and
      suppressed gastric cancer cell growth, indicating that the inhibitory effect of
      SC-236 on AP-1 activation and cell growth was through interaction with JNK.
      CONCLUSIONS: The inhibitory effect on JNK-c-Jun/AP-1 activation contributes to
      the antitumor effect of COX-2-specific inhibitor, and inhibition of JNK
      activation may have a therapeutic benefit against gastric cancer.

PMID- 14699496
TI  - Extracellular polyamines regulate fluid secretion in rat colonic crypts via the
      extracellular calcium-sensing receptor.
AB  - BACKGROUND AND AIMS: Polyamines are essential for the normal postnatal
      development, maintenance, and function of gastrointestinal epithelia. The
      extracellular Ca(2+) (Ca(2+)(o)/nutrient)-sensing receptor is expressed on both
      luminal and basolateral membranes of colonocytes, and, in other cell systems,
      this receptor has been shown to respond to polyamines. Thus, the Ca(2+)-sensing
      receptor could provide a mechanism for modulation of colonocyte function by
      dietary and systemic extracellular polyamines. In the present study, we
      investigated the interaction of polyamines, particularly spermine, and
      extracellular Ca(2+) on second messenger generation by, and on function of, rat
      distal colonic crypts. METHODS: Calcium-sensing receptor activation was assessed
      in colonic epithelial cells and intact crypts freshly isolated from distal colon
      by monitoring intracellular IP(3) and Ca(2+) accumulation using radioimmunoassay
      and Fluo-3 fluorometry, respectively. Interactions of extracellular Ca(2+) and
      spermine on regulation of both basal and forskolin-stimulated fluid transport
      were measured in crypts microperfused in vitro. RESULTS: Polyamine (spermine >
      spermidine > putrescine)-mediated enhancement of intracellular D-myo-inositol
      1,4,5-trisphosphate (IP(3)) and Ca(2+) accumulation required extracellular
      Ca(2+), and the EC(50) for extracellular Ca(2+)-mediated activation of the
      calcium-sensing receptor was reduced by polyamines. Extracellular spermine
      modulated both basal and forskolin-stimulated fluid secretion in perfused colonic
      crypts, and the EC(50) for spermine-induced reduction in forskolin-stimulated
      fluid secretion was inversely dependent on extracellular Ca(2+) (Ca(2+)(o)).
      CONCLUSIONS: The interactions of extracellular Ca(2+) and polyamines on second
      messenger accumulation and fluid secretion support a role for the luminal and
      basolateral calcium-sensing receptors in mediating some of the effects of
      polyamines on distal colonic epithelial cells.

PMID- 14699497
TI  - Selective jejunal manipulation causes postoperative pan-enteric inflammation and
      dysmotility.
AB  - BACKGROUND AND AIMS: Small bowel manipulation initiates an intense molecular and
      cellular inflammatory response within the jejunal muscularis, which causes ileus.
      The current objective was to investigate pan-enteric inflammatory molecular and
      functional motility alterations of the muscularis from the unmanipulated stomach
      and colon initiated by selective jejunal manipulation. METHODS: Rat jejunum was
      manipulated, and animals sacrificed between 0-24 hours. In vivo gastric emptying,
      gastrointestinal transit, and in vitro colonic circular muscle recordings were
      measured. Reverse-transcriptase polymerase chain reaction (RT-PCR) and
      electromobility shift assay (EMSA) of gastric, jejunal, and colonic muscularis
      extracts were performed. Whole mounts were histochemically stained for
      myeloperoxidase leukocytes. RESULTS: Surgical manipulation suppressed jejunal
      contractions that were significantly prevented by dexamethasone pretreatment.
      Selective jejunal manipulation also suppressed in vivo gastric emptying,
      gastrointestinal transit, and in vitro colonic circular muscle contractility.
      Nuclear factor interleukin-6 (NF-IL-6) was activated within the gastric and
      colonic muscularis. RT-PCR showed a 14.9-, 8.1-, and 11.4-fold up-regulation of
      IL-6 messenger RNA within the jejunal, gastric, and colonic muscularis,
      respectively. EMSA showed a 30.6-, 14.2-, and 20.8-fold increased activation of
      signal transducer and activator of transcription (STAT) proteins in jejunal,
      gastric, and colonic muscularis extracts, respectively. Tumor necrosis factor
      alpha, cyclooxygenase-2, and inducible nitric oxide synthase showed a significant
      up-regulation in the manipulated jejunum, as well as the unmanipulated gastric
      and colonic muscularis. Neutrophils were significantly recruited into all
      gastrointestinal regions. CONCLUSION: Selective small bowel manipulation leads to
      a molecular, cellular, and functional pan-enteric "field effect" phenomenon in
      the unmanipulated gastric and colonic muscularis.

PMID- 14699498
TI  - Exacerbated colitis associated with elevated levels of activated CD4+ T cells in
      TCRalpha chain transgenic mice.
AB  - BACKGROUND AND AIMS: An unconventional CD4+ TCRalpha(-)beta(+) cell population
      mediates the development of colitis resembling ulcerative colitis in T-cell
      receptor alpha mutant (TCRalpha(-/-)) mice. However, the significance of such T
      cells in individuals with an intact TCRalpha locus remains unclear. Because a
      substantial proportion of naturally rearranged TCRalpha chains fails to pair with
      TCRbeta chains, the aim of this study was to analyze the development of CD4+
      TCRalpha(-)beta(+) cells and the course of colitis in the presence of such a
      TCRalpha chain. METHODS: TCR chain transgenic TCRalpha(-/-) mice were generated
      and compared with wild-type and TCRalpha(-/-) mice by flow cytometric analysis of
      T lymphocytes with respect to their TCR expression and activation status and by
      histological analysis of colon tissue. The colitogenic potential of the
      unconventional CD4+ TCRalpha(-)beta(+) cells was assessed by adoptive transfer
      experiments. Furthermore, the half-life of TCRbeta chains was determined by pulse
      chase labeling and immunoprecipitation. RESULTS: Transgenic expression of a TCR
      Valpha7.2 chain led to increased frequencies of CD4+ TCRalpha(-)beta(+) cells
      that caused rapid onset of colitis, reminiscent of, but even more severe than,
      that in TCRalpha(-/-) mice. This unconventional T-cell population displayed a
      constitutively activated phenotype in normal and transgenic TCRalpha(-/-) mice.
      An extended half-life of newly synthesized TCRbeta chains suggests a chaperone
      function of the TCR Valpha7.2 chain in TCRalpha(-/-) mice. CONCLUSIONS:
      Physiological TCRalpha rearrangement can promote the formation of chronically
      activated CD4+ TCRalpha(-)beta(+) T cells and may play a role in the etiology of
      UC.

PMID- 14699499
TI  - Divalent cations regulate acidity within the lumen and tubulovesicle compartment
      of gastric parietal cells.
AB  - BACKGROUND & AIMS: Until recently, it has not been possible to evaluate factors
      that regulate the acidity of the microenvironment within the tubulovesicles and
      luminal (TV/L) spaces of the gastric gland. The goal of this study was to develop
      a method for monitoring the mechanisms that regulate acidity in the TV/L
      compartment. METHODS: Isolated rabbit gastric glands (intact or permeabilized
      with S. aureus alpha-toxin) were loaded with a recently characterized fluorescent
      dye, LysoSensor Yellow-Blue DND 160 (Molecular Probes, Eugene, OR), which
      localizes to highly acidic compartments and can be used to monitor acidity
      ratiometrically. RESULTS: In resting glands, the pH of the TV/L compartment was
      approximately 3.4. Moderate alkalizations ( approximately 0.5 to 1.0 pH unit
      alkalization) were observed during exposure to inhibitors of the apical H(+)/K(+)
      ATPase (omeprazole and SCH28080), thereby unmasking a stable, low-level leak of
      H(+) ions from the TV/L compartment. Similar changes were observed in alpha-toxin
      permeabilized glands following depletion of ATP in the cytoplasm. In intact and
      permeabilized glands, we used the cell-permeant, divalent cation chelator,
      tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) to probe the effects of lowering
      divalent cation content of the TV/L compartment. Exposure to relatively low
      concentrations (20 micromol/L, 50 micromol/L) of TPEN reversibly promoted H(+)
      leakage. At these concentrations, simultaneous inhibition using SCH28080 led to
      marked enhancement of the rate of alkalization. CONCLUSIONS: The effects of low
      dose TPEN suggests that acidity within the TV/L compartment of the gastric gland
      may be regulated, at least in part, by its content of divalent cations such as
      Zn(2+), for which TPEN has high affinity.

PMID- 14699500
TI  - Gastric cancer development in mice lacking the SHP2 binding site on the IL-6
      family co-receptor gp130.
AB  - BACKGROUND AND AIMS: We have developed a mouse model of gastric cancer that
      resembles human intestinal-type adenocarcinoma. The aim of this study was to
      determine the identity and temporal changes in mediators of IL-6 signaling
      regulating tumor development. METHODS: gp130(757F/F) Mice that lack the SHP2
      binding site on the IL-6 family receptor gp130 and have increased STAT 3 activity
      and wild-type littermates were used. Cohorts were assessed by quantitative
      histology and immunohistochemistry for gastric cell phenotype and proliferation
      markers from 4 to 40 weeks of tumor development. Northern blotting and in situ
      hybridization were used to quantify expression of the tumor suppressor TFF1 and
      the mitogens gastrin and Reg I. Expression of epidermal growth factor receptor
      (EGFr) and its ligands was measured by RT-PCR analysis. Age-matched differences
      in gene expression profiles were tested by ANOVA. RESULTS: Hyperplastic antral
      tumors with inflammation and ulceration were evident in gp130(757F/F) mice at 4
      weeks of age and reached maximum size by 20 weeks. Tumor progression was marked
      by gastritis, atrophy, intestinal metaplasia, dysplasia, and submucosal invasion
      after 30 weeks. Both TFF1 and gastrin expression were progressively inhibited
      during tumorigenesis, whereas Reg I was stimulated. The EGFr and its ligands
      transforming growth factor (TGF)-alpha and heparin-binding EGF had increased
      expression corresponding to maximal tumor growth. CONCLUSIONS: gp130(757F/F) Mice
      rapidly develop distal stomach tumors, with loss of SHP2/Erk/AP-1 transcriptional
      regulation exemplified by decreased TFF1 expression and increased STAT1/3
      regulated genes such as Reg I. Tumor development occurs in a hypogastrinemic
      environment. Balanced IL-6 signaling is required for maintaining gastric
      homeostasis.

PMID- 14699501
TI  - A protective role of protease-activated receptor 1 in rat gastric mucosa.
AB  - BACKGROUND AND AIMS: On activation, protease-activated receptor (PAR)-2 modulates
      multiple gastric functions and exerts mucosal protection via activation of
      sensory neurons. The role of PAR-1, a thrombin receptor, in the stomach remains
      unknown. We thus examined if the PAR-1 agonist could protect against gastric
      mucosal injury in rats. METHODS: Gastric mucosal injury was created by oral
      administration of ethanol/HCl or absolute ethanol in conscious rats. Gastric
      mucosal blood flow and acid secretion were determined in anesthetized rats.
      Immunohistochemical analyses of PAR-1 and cyclooxygenase (COX)-1 were also
      performed in rat and human stomach. RESULTS: The PAR-1 agonist TFLLR-NH(2),
      administered intravenously in combination with amastatin, protected against the
      gastric mucosal injury induced by ethanol/HCl or absolute ethanol. The protective
      effect of TFLLR-NH(2) was abolished by indomethacin or a COX-1 inhibitor but not
      by ablation of sensory neurons with capsaicin. TFLLR-NH(2) produced an NO
      independent increase in gastric mucosal blood flow that was partially inhibited
      by blockade of the endothelium-derived hyperpolarizing factor pathway. This
      inhibitory effect was promoted by indomethacin. TFLLR-NH(2) suppressed carbachol
      evoked acid secretion in an indomethacin-reversible manner. Immunoreactive PAR-1
      and COX-1 were expressed abundantly in rat gastric muscularis mucosae and smooth
      muscle, and the former protein was also detectable in blood vessels. Similar
      staining was observed in human gastric muscularis mucosae. CONCLUSIONS: The PAR-1
      agonist, given systemically, protects against gastric mucosal injury via COX-1
      dependent formation of prostanoids, modulating multiple gastric functions. Our
      data identify a novel protective role for PAR-1 in gastric mucosa, and the
      underlying mechanism is entirely different from that for PAR-2.

PMID- 14699502
TI  - Bax is required for resection-induced changes in apoptosis, proliferation, and
      members of the extrinsic cell death pathways.
AB  - BACKGROUND AND AIMS: To define better the homeostatic mechanisms contributing to
      small intestinal adaptation following partial resection, the relative
      contributions of apoptosis, cell proliferation, and enterocyte migration and the
      comparative roles of the intrinsic (mitochondrial) and extrinsic (death receptor
      mediated) apoptotic pathways were assessed. METHODS: After 50% jejunoileal
      resections or transections, adaptation was analyzed in duodenal-jejunal and ileal
      segments from C57BL/6 Bax(+/+) (16, 48, and 168 hours postoperative) and Bax(-/-)
      mice (168 hours). RESULTS: Basal apoptotic rates were equivalent in all mice. By
      1-week postresection, villus heights and crypt depths were increased in the
      duodenal-jejunal and ileal remnants of both genotypes. In Bax(+/+) mice,
      adaptation occurred in concert with increased crypt proliferative and apoptotic
      indices. Bax(-/-) mice did not show increases in proliferation or apoptosis, yet
      adaptive increases in villus height were enhanced relative to Bax(+/+) mice.
      Enterocyte migration increased in both genotypes. Postresection, the expression
      of caspases and genes involved in death receptor-mediated apoptosis was decreased
      in Bax(-/-) compared with Bax(+/+) mice. CONCLUSIONS: Postresection adaptation
      involves parallel changes in crypt proliferation and apoptosis, but, as observed
      in Bax(-/-) mice, it can occur without increased proliferation. These studies
      demonstrate that spontaneous gut apoptosis is Bax independent, whereas adaptation
      related apoptosis is Bax-dependent. Differences between resected Bax(+/+) and
      Bax(-/-) mice suggest that apoptosis in the adapting gut utilizes the extrinsic
      pathway, but this requires linkage to the mitochondrial pathway via Bax. The
      increased adaptive response in Bax(-/-) mice indicates that modulation of
      apoptosis may be useful for enhancing adaptation.

PMID- 14699503
TI  - hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing
      heparin-binding growth factor signaling.
AB  - BACKGROUND AND AIMS: The heparin-binding growth factors fibroblast growth factor
      (FGF) and hepatocyte growth factor (HGF) are potent mitogens for hepatocellular
      carcinomas (HCCs). Heparin-binding growth factor signaling is regulated by
      sulfation of cell-surface heparan sulfate proteoglycans (HSPGs). We hypothesized
      that hSulf1, a recently described sulfatase, regulates growth signaling in HCCs.
      METHODS: Expression of hSulf1 in human HCC tumors was determined by real-time
      PCR. Down-regulation of hSulf1 expression was investigated by analyzing loss of
      heterozygosity (LOH) at the hSulf1 locus and the effect of the DNA methylation
      inhibitor 5-aza-deoxycytidine on hSulf1 expression. The subcellular location of
      hSulf1 and sulfation state of cell-surface HSPGs were assessed by
      immunocytochemistry. FGF and HGF signaling was examined by phospho-specific
      immunoblot analysis. Cell growth was measured by trypan blue exclusion, and the
      MTT assay and apoptosis were quantitated by fluorescence microscopy. RESULTS:
      hSulf1 expression was decreased in 29% of HCCs and 82% of HCC cell lines. There
      was LOH at the hSulf1 locus in 42% of HCCs. Treatment with 5-aza-deoxycytidine
      reactivated hSulf1 expression in hSulf1-negative cell lines. Low hSulf1
      expressing cells showed increased sulfation of cell-surface HSPGs, enhanced FGF
      and HGF-mediated signaling, and increased HCC cell growth. Conversely, forced
      expression of hSulf1 decreased sulfation of cell-surface HSPGs and abrogated
      growth signaling. HCC cells with high-level hSulf1 expression were sensitive to
      staurosporine- or cisplatin-induced apoptosis, whereas low expressing cells were
      resistant. Transfection of hSulf1 into hSulf1-negative cells restored
      staurosporine and cisplatin sensitivity. CONCLUSIONS: Down-regulation of hSulf1
      contributes to hepatocarcinogenesis by enhancing heparin-binding growth factor
      signaling and resistance to apoptosis.

PMID- 14699504
TI  - Inhibition of bile salt-induced apoptosis by cyclic AMP involves serine/threonine
      phosphorylation of CD95.
AB  - BACKGROUND AND AIMS: Cyclic AMP (cAMP) inhibits bile salt-induced hepatocyte
      apoptosis; the underlying mechanisms are unclear. METHODS: The effects of cAMP on
      taurolithocholate-3-sulfate-(TLCS)- or glycochenodesoxycholate (GCDC)-induced
      CD95 (Fas/APO-1) activation and apoptosis were studied in 24-hour cultured rat
      hepatocytes and in perfused rat liver. RESULTS: TLCS induced a rapid oxidative
      stress response, c-Jun-N-terminal kinase (JNK) and epidermal growth factor (EGF)
      receptor (EGF-R) activation, subsequent EGF-R/CD95 association and CD95 tyrosine
      phosphorylation, CD95 membrane targeting, death-inducing signal complex (DISC)
      formation and hepatocyte apoptosis. None of these responses was triggered by
      cAMP; however, cAMP induced H89-sensitive serine/threonine phosphorylation of
      CD95. Similar data were obtained with GCDC, another proapoptotic bile acid. cAMP
      did not prevent the TLCS-induced oxidative stress response, JNK activation and
      EGF-R/CD95 association, however abolished EGF-R activation and subsequent CD95
      tyrosine phosphorylation, CD95 membrane trafficking, and DISC formation in a H89
      sensitive way. Also in presence of TLCS, cAMP induced rapid Ser/Thr
      phosphorylation of CD95 within 10 min. The effects of cAMP on the various steps
      of CD95 activation were also found in the intact perfused rat liver. Evidence is
      given that a cAMP-induced Ser/Thr phosphorylation favors internalization of CD95.
      CONCLUSIONS: Inhibition of bile salt-induced apoptosis by cAMP involves both PKA
      dependent Ser/Thr phosphorylation of the CD95 and inhibition of EGF-R activation,
      which results in an inhibition of CD95 tyrosine phosphorylation, CD95 membrane
      targeting, and DISC formation. CD95 regulation involves complex phosphorylations
      with CD95-tyrosine phosphorylation favoring CD95 membrane trafficking and DISC
      formation, whereas CD95 Ser/Thr phosphorylation inhibits these processes.

PMID- 14699505
TI  - Hepatitis C virus inhibits interferon signaling through up-regulation of protein
      phosphatase 2A.
AB  - BACKGROUND AND AIMS: To establish a chronic infection, hepatitis C virus (HCV)
      has to evade the host defense. Expression of HCV proteins in cultured cells and
      in hepatocytes of transgenic mice inhibits interferon-alpha-induced intracellular
      signaling through the Jak-STAT (signal transducer and activator of transcription)
      pathway. It is not known if interferon-alpha signaling is inhibited in patients
      with chronic hepatitis C as well, and the molecular mechanisms are not well
      defined. METHODS: Interferon-alpha-induced signaling was investigated in liver
      biopsies from patients with chronic hepatitis C. The molecular mechanisms of HCV
      interference with Jak-STAT signaling were analyzed in cultured cells, HCV
      transgenic mice, and liver biopsies. RESULTS: Interferon-alpha-induced DNA
      binding of STAT1 was significantly impaired in liver biopsies from patients with
      chronic hepatitis C compared with controls. Tyrosine and serine phosphorylation
      of STAT1 were intact, but methylation of STAT1 on arginine 31 was reduced.
      Hypomethylated STAT1 associated with PIAS1, an inhibitor of STAT DNA binding.
      Increased expression levels of Protein Phosphatase 2A were found in liver
      extracts from HCV transgenic mice and in liver biopsies of patients with chronic
      hepatitis C. Overexpression of PP2Ac in Huh7 cells resulted in hypomethylation of
      STAT1, increased binding to PIAS1, and reduced interferon-alpha-induced DNA
      binding of STAT1. CONCLUSIONS: We conclude that HCV interferes with interferon
      alpha signaling via up-regulation of PP2Ac, hypomethylation of STAT1, and
      increased STAT1-PIAS1 association, resulting in reduced transcriptional
      activation of interferon-alpha-stimulated genes.

PMID- 14699506
TI  - Prolonged and inducible transgene expression in the liver using gutless
      adenovirus: a potential therapy for liver cancer.
AB  - BACKGROUND AND AIMS: Gene therapy of liver diseases would benefit from systems
      allowing prolonged, regulable, and tissue-specific transgene expression. We
      attempted to produce a vector fulfilling these requirements. METHODS: We
      generated gutless adenoviral vectors containing a mifepristone (RU486)-inducible
      system for controlled and liver-specific expression of human interleukin-12 (hIL
      12) (GL-Ad/RUhIL-12) and mouse IL-12 (mIL-12) (GL-Ad/RUmIL-12). The properties of
      these vectors were tested both in vitro and in vivo. RESULTS: Infection of cells
      with GL-Ad/RUhIL-12 resulted in high level of hIL-12 expression in the presence
      of RU486 only in hepatocytic cells. In animals injected with GL-Ad/RUhIL-12, the
      administration of RU486 induced a transient rise of serum hIL-12 that peaked at
      10 hours and completely disappeared by 72 hours. The peak value of hIL-12 was
      dependent on the doses of the vector and the inducer. High and sustained serum
      levels of hIL-12 could be attained by continuing administration of RU486 every 12
      or 24 hours. Repetitive induction of hIL-12 could be obtained over, at least, a
      period of 48 weeks after a single injection of GL-Ad/RUhIL-12. Although the
      vector was detected in many tissues after systemic injection, transcription of
      the transgene was only found in the liver. Treatment of liver metastases with 5 x
      10(8) infectious units of GL-Ad/RUmIL-12 plus RU846 resulted in complete tumor
      regression in all animals. CONCLUSION: Gutless adenoviral vectors allow liver
      specific and regulable transgene expression for prolonged periods of time. These
      vectors are promising tools for gene therapy of liver cancer and could also be
      useful for other forms of hepatic disease.

PMID- 14699507
TI  - Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation
      of the liver-X receptor.
AB  - BACKGROUND AND AIMS: Mutations in either adenosine triphosphate- binding cassette
      (ABC) half-transporter G5 or G8 cause sitosterolemia. It has been proposed that
      ABCG5/ABCG8 heterodimers mediate secretion of plant sterols and cholesterol by
      hepatocytes into bile and their efflux from enterocytes into the intestinal
      lumen. METHODS: To test whether deficiency of ABCG5 alone is sufficient to induce
      sitosterolemia, Abcg5-null mice were generated and characterized with respect to
      sterol metabolism. RESULTS: Abcg5 deficiency was associated with strongly
      elevated plasma levels of beta-sitosterol (37-fold) and campesterol (7.7-fold) as
      well as reduced plasma cholesterol concentrations (-40%). Retention of orally
      administered [(3)H]beta-sitosterol in the intestinal wall (+550%) and plasma
      (+640%) was higher in Abcg5-null mice than in wild-type controls. Surprisingly,
      high plasma beta-sitosterol and campesterol concentrations were even further
      elevated in Abcg5-null mice on treatment with the synthetic LXR agonist T0901317
      (0.015% dietary supplementation, 10 days), whereas these concentrations were
      reduced by approximately 75% in wild-type mice. Both cholesterol and phospholipid
      concentrations in gallbladder bile were decreased, but, unexpectedly,
      cholesterol/phospholipid ratios were unchanged in the absence of Abcg5 and
      increased in both genotypes on LXR activation. Hepatic expression of Abcg8 was
      reduced by about 35% in Abcg5-deficient mice when compared with controls. No
      compensatory overexpression of other ABC transporters potentially involved in
      hepatic cholesterol trafficking was observed on messenger RNA level. CONCLUSIONS:
      Our data show that disruption of the Abcg5 gene alone is sufficient to cause
      hyperabsorption of dietary plant sterols and sitosterolemia in mice, whereas the
      ability to secrete cholesterol into bile is maintained.

PMID- 14699508
TI  - The incidental upper gastrointestinal subepithelial mass.

PMID- 14699509
TI  - Hereditary persistence of alpha-fetoprotein is due to both proximal and distal
      hepatocyte nuclear factor-1 site mutations.
AB  - BACKGROUND AND AIMS: The molecular mechanism of hereditary persistence of alpha
      fetoprotein (HPAFP) has been previously described in a large Scottish family,
      consisting of a -119G>A substitution in the distal hepatocyte nuclear factor 1
      (HNF-1) binding site of the alpha-fetoprotein (AFP) gene promoter. We report here
      the molecular mechanisms of HPAFP in 2 new unrelated families. METHODS: Family 1
      was of Bengali origin, and family 2 was Italian. Four of 5 subjects (family 1)
      and 3 of 9 (family 2) showed HPAFP. The AFP gene promoter was studied in all
      available family members. RESULTS: All subjects with high AFP levels had mutated
      promoter sequences. Family 1 showed the reported -119G>A substitution. Family 2
      showed -55C>A and -65C>T substitutions in the proximal putative HNF-1 binding
      region of the promoter. The -55C>A mutation increased the similarity of the
      proximal HNF-1 binding region to a consensus binding region. Gel shift assays
      confirmed its increased affinity toward HNF-1, and transfection experiments
      revealed an increased level of gene transcription. The -65C>T substitution
      theoretically created a CCAAT box. However, gel shift and transfection
      experiments failed to show any biological effect of this substitution that is
      associated with the -55C>A mutation. CONCLUSIONS: Two different mutations
      localized in either HNF-1 binding sites of the AFP gene promoter may result in
      HPAFP. This highlights the importance of HNF-1 in AFP gene expression.
      Unexplained persistent AFP should lead to family study and/or AFP gene promoter
      sequencing to avoid inappropriate explorations and treatment decisions.

PMID- 14699510
TI  - PDGFRA germline mutation in a family with multiple cases of gastrointestinal
      stromal tumor.
AB  - Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant
      genetic disorder associated with KIT germline mutations. In sporadic forms of the
      disease, somatic mutations target either KIT or PDGFRA genes. In a kindred in
      which 5 individuals had GIST, no germline mutation in KIT coding sequence has
      been detected. We hypothesized that the PDGFRA gene could be a predisposing gene
      in familial GIST. We sequenced PDGFRA exons 12 and 18 because several somatic
      mutations were identified within this region. We detected a germline PDGFRA
      missense mutation, 2675G > T, resulting in a tyrosine substitution for the highly
      conserved aspartic acid at codon 846. This mutation showed perfect cosegregation
      with the GIST phenotype among the 7 family members tested. Interestingly, PDGFRA
      Asp846 is homologous to codon 820, which is located in the KIT tyrosine kinase II
      domain. In a previous study, a KIT germline Asp820Tyr mutation was detected in a
      Japanese kindred in which 6 individuals had GIST. Transfection of a KIT820Tyr
      complementary DNA in nude mice was found to be tumorigenic confirming the
      oncogenic potential of this mutation. The present study shows that PDGFRA is a
      second familial GIST predisposing gene. These results indicate a further example
      of involvement of structurally related genes in familial cancer syndromes.

PMID- 14699511
TI  - Enterohepatic bile salt transporters in normal physiology and liver disease.
AB  - The vectorial transport of bile salts from blood into bile is essential for the
      generation of bile flow, solubilization of cholesterol in bile, and
      emulsification of lipids in the intestine. Major transport proteins involved in
      the enterohepatic circulation of bile salts include the hepatocellular bile salt
      export pump (BSEP, ABCB11), the apical sodium-dependent bile salt transporter
      (ASBT, SLC10A2) in cholangiocytes and enterocytes, the sodium-dependent
      hepatocyte bile salt uptake system NTCP (SLC10A1), the organic anion transporting
      polypeptides OATP-C (SLC21A6), OATP8 (SLC21A8) and OATP-A (SLC21A3), and the
      multidrug resistance protein MRP3 (ABCC3). Synthesis and transport of bile salts
      are intricately linked processes that undergo extensive feedback and feed-forward
      regulation by transcriptional and posttranscriptional mechanisms. A key regulator
      of hepatocellular bile salt homeostasis is the bile acid receptor/farnesoid X
      receptor FXR, which activates transcription of the BSEP and OATP8 genes and of
      the small heterodimer partner 1 (SHP). SHP is a transcriptional repressor that
      mediates bile acid-induced repression of the bile salt uptake systems rat Ntcp
      and human OATP-C. A nuclear receptor that activates rodent Oatp2 (Slc21a5) and
      human MRP2 (ABCC2) is the pregnane X receptor/steroid X receptor PXR/SXR.
      Intracellular trafficking and membrane insertion of bile salt transporters is
      regulated by lipid, protein, and extracellular signal-related kinases in response
      to physiologic stimuli such as cyclic adenosine monophosphate or taurocholate.
      Finally, dysfunction of individual bile salt transporters such as BSEP, on
      account of genetic mutations, steric inhibition, suppression of gene expression,
      or disturbed signaling, is an important cause of cholestatic liver disease.

PMID- 14699512
TI  - Rescue therapy for drug resistant hepatitis B: another argument for combination
      chemotherapy?

PMID- 14699513
TI  - Occult hepatitis B virus infection in patients with hepatocellular carcinoma:
      Innocent bystander, cofactor, or culprit?

PMID- 14699514
TI  - The impact of antireflux surgery on Barrett's esophagus.

PMID- 14699516
TI  - Preventing colitis through alteration of the intestinal biota.

PMID- 14699517
TI  - What's the point of analgesia?

PMID- 14699519
TI  - Intrahepatic gene silencing by RNA interference.

PMID- 14699521
TI  - The iceberg cometh: establishing the prevalence of celiac disease in the United
      States and Finland.

PMID- 14699539
TI  - What about tomorrow? The need for scientifically based long-range planning for
      the future of oral and maxillofacial surgery.

PMID- 14699540
TI  - Postoperative prophylactic antibiotic treatment in third molar surgery--a
      necessity?
AB  - PURPOSE: We evaluated the need for prophylactic postoperative oral antibiotic
      treatment in the removal of asymptomatic third molars. MATERIALS AND METHODS: In
      a prospective study of more than 30 months, a total of 528 impacted lower third
      molars were surgically removed in 288 patients. All patients were referred to our
      department by a dentist or a general practitioner. No patient showed any sign of
      pain, inflammation, or swelling at the time of removal. Three groups were
      established. In the first group, antibiotic treatment with amoxicillin/clavulanic
      acid as an oral medication was carried out for 5 days postoperatively. In the
      second group, we used clindamycin. In the third group, the patients received no
      antibiotic treatment. Clinical and radiologic factors were recorded for each
      case, and the rationale for assigning the patients to the groups was strictly
      random. The surgical technique was the same in all cases, and the follow-up
      period was 4 weeks. Parameters that were evaluated were pain, differences in
      mouth opening, infection, the occurrence of dry socket, and adverse postoperative
      side effects. RESULTS: We could not find any significant difference between the 3
      groups regarding the evaluated parameters, but in 69.6% of the patients with dry
      socket, the teeth were partially erupted, which showed a significant difference.
      CONCLUSIONS: The results of our study show that specific postoperative oral
      prophylactic antibiotic treatment after the removal of lower third molars does
      not contribute to a better wound healing, less pain, or increased mouth opening
      and could not prevent the cases of inflammatory problems after surgery,
      respectively, and therefore is not recommended for routine use.

PMID- 14699542
TI  - The relationship of "shisha" (water pipe) smoking to postextraction dry socket.
AB  - PURPOSE: This study was undertaken to determine whether "shisha" (water pipe)
      smokers (SS) were at a different risk of developing dry socket (DS) than were
      cigarette smokers (CS) or nonsmokers (NS) and to assess the effect of
      preoperative and postoperative smoking habits on the incidence of DS. MATERIALS
      AND METHODS: One hundred NS, 100 CS, and 100 SS were enrolled. Surgery for
      removal of mandibular third molars was performed under local anesthesia with no
      incision or bone removal. At 1, 4, and 7 days after surgery, postoperative
      evaluation and postoperative smoking were recorded by the same examiner. The
      chi(2) test was used for statistical analysis of results. Statistical
      significance was defined as a value of P <.05. RESULTS: Smokers had 2 to 3 times
      the risk of NS for developing DS. Although SS had a greater incidence of DS than
      did CS, the difference was not significant (P =.083). The incidence of DS was not
      age dependent. Smokers who smoked the day of surgery had a significantly higher
      incidence of DS than did smokers who smoked the second day after surgery.
      Compared with NS, CS who smoked the day of surgery and SS who smoked the day of
      surgery or the first day after surgery had a significantly increased incidence of
      DS (CS/NS, day 0, P =.001; SS/NS, day 0, P =.001; day 1, P =.005). CONCLUSION: SS
      had 3 times the risk of NS for developing DS, but there was no statistically
      significant difference between SS and CS. Increased frequency of smoking and
      smoking during the day of surgery significantly increased the incidence of DS.

PMID- 14699543
TI  - The impact of intravenous antibiotics on health-related quality of life outcomes
      and clinical recovery after third molar surgery.
AB  - PURPOSE: We sought to compare recovery for clinical and health-related quality of
      life (HRQOL) outcomes after third molar surgery in patients treated with or
      without intravenous antibiotics at surgery. PATIENTS AND METHODS: Fifty-six
      patients at least 18 years of age and with all 4 third molars below the occlusal
      plane, treated at 3 clinical centers, were given intravenous antibiotics just
      before third molar surgery. Clinical and HRQOL outcomes of these patients were
      compared with those of a nonconcurrent control group (n = 60 patients) who did
      not receive antibiotics. The control group was selected using the same criteria
      and treated under the same surgical protocol as the antibiotic group. Differences
      between the groups were assessed with Cochran-Mantel-Haenszel row mean score
      statistics. RESULTS: The incidence of delayed clinical recovery defined as a
      postsurgery visit with treatment was higher in the control group compared with
      the antibiotic group. In the antibiotic group, 4% had 1 postsurgery visit with
      treatment; no patient had 2 visits. In the control group without antibiotics, 28%
      had at least 1 postsurgery visit with treatment (P <.0001) and 13% had at least 2
      postsurgery visits with treatment. No statistically significant differences in
      HRQOL outcomes were found between the 2 groups. CONCLUSIONS: Administration of
      intravenous antibiotics before third molar surgery may improve clinical recovery
      in healthy adult patients with all 4 third molars below the occlusal plane, a
      presenting characteristic that has been suggested as a risk factor for delayed
      recovery. The findings from this exploratory trial indicate that evaluation of
      the effectiveness of systemic antibiotic administration with third molar surgery
      in a randomized, multi-intervention, explanatory clinical trial is warranted.

PMID- 14699544
TI  - Proximal segment positioning in bilateral sagittal split osteotomy:
      intraoperative dynamic positioning and monitoring by sonography.
AB  - PURPOSE: Most methods of condylar positioning merely maintain the preoperative
      condyle-fossa relationship and therefore produce similar prevalences of
      postoperative dysfunction. This study evaluates dynamic proximal segment
      positioning by intraoperative sonography versus the splint and plate technique
      discussed in a previous issue. PATIENTS AND METHODS: Condylar positioning was
      monitored by sonography alone in 30 bimaxillary operated patients (14 Angle Class
      II, 16 Class III), the control group had a splint and plate positioning in 23
      patients (9 Angle Class II, 14 Class III). The clinical dysfunction index,
      prevalence of condylar translation, and disc dislocation were compared
      preoperatively and at 1, 6, and 12 months postoperatively. RESULTS: The
      postoperative range of motion did not disclose statistically significant
      differences between study and control group (Pearson's proportionality index r =
      0.78, 2-way analysis of variance: P <.4, F = 4.4, alpha =.05 significance level).
      Sonographic placement allowed dynamic intraoperative monitoring of the condylar
      position and required an average of 5 minutes compared with 25 minutes for
      conventional positioning. Postoperative dysfunction prevalence was reduced 89%
      for Class II and 100% in Class III in the study group versus 50% for Class II and
      100% for Class III in the control group (r = 0.45, P <.3, F = 9.3). Prevalence of
      disc dislocation was reduced 76% in Class II and 80% in Class III patients in the
      study group and 50% of Class II and 100% of Class III in the control group (r =
      0.7, P <.48, F = 9.2). CONCLUSIONS: Comparable postoperative reduction of
      condylar translation and recovery, dysfunction, and disc dislocation was seen
      with use of both methods in a 1-year follow-up. The new technique allowed
      intraoperative real-time monitoring and dynamic correction and was safe, easier,
      and faster than conventional plate positioning.

PMID- 14699545
TI  - Reconstruction of skull bone defects using the hydroxyapatite cement with
      calvarial split transplants.
AB  - PURPOSE: We sought to present a new method for primary reconstruction of
      traumatic or tumor calvarial defects. PATIENTS AND METHODS: Forty-one patients
      underwent reconstruction of calvarial bone defects between October 1998 and
      December 2001. Among them were 19 patients who needed reconstruction of the
      calvaria due to traumatic bone loss. Five of these trauma cases had insufficient
      primary reconstruction of the calvaria. Tumor resection caused calvarial defects
      in 22 patients. For primary reconstruction of the skull bone defects, calvarial
      split grafts were used to cover the defect as accurately as possible. The
      monocortical layers of the calvaria were fixed with titanium miniplates.
      Irregular defects surrounding the transplanted regions were filled with
      hydroxyapatite cement. In one case of posttraumatic bone loss, hydroxyapatite
      cement alone was sufficient to reconstruct the defect. RESULTS: The follow-up of
      each patient was at least 6 months; the longest period was 38 months. Evaluated
      clinical and radiologic results are stable, showing no measurable side effects.
      CONCLUSION: Hydroxyapatite cement alone or in combination with calvarial split
      grafts gave clinically and aesthetically stable results in the reconstruction of
      skull bone defects. The cement can be used for many reconstruction possibilities
      in craniofacial surgery.

PMID- 14699546
TI  - Trauma from tire and rim explosions: A retrospective analysis.
AB  - PURPOSE: The purpose of this study is to review injuries occurring as a result of
      tire and rim explosions treated at a level I trauma center. MATERIALS AND
      METHODS: The retrospective audit evaluated the university hospital trauma
      database based on ICD-9 code to isolate patients sustaining tire and rim
      explosion injuries. A total of 12 complete patient records were derived from this
      search to allow determination of injuries and outcome assessments. RESULTS:
      Injury patterns from tire and rim explosions were categorized in terms of
      anatomic region, treatment and hospitalization, disposition, and outcome
      assessment. Maxillofacial injuries were further subdivided into specific injuries
      involving a total of 7 patients from this case series. CONCLUSIONS: Significant
      blast injuries can result from tire and rim explosions, which can often involve
      the maxillofacial region due to proximity to the source. Reductions in injuries
      have been seen since the implementation of physical safety measures by the
      Occupational Safety and Health Administration and the National Highway
      Transportation Safety Board.

PMID- 14699547
TI  - A comparative assessment of mandibular condylar position in patients with
      anterior disc displacement of the temporomandibular joint.
AB  - PURPOSE: The purpose of this study was to determine whether the position of the
      mandibular condyle in patients with anterior disc displacement (ADD) is different
      from that of a control group with normal joints using a novel method to quantify
      the irregular shape of the temporomandibular joint (TMJ). MATERIALS AND METHODS:
      Twenty-six magnetic resonance images of TMJs with ADD were evaluated and compared
      with 14 normal joints. The position of the condyle was determined by using 2
      different methods: 1) measuring the horizontal and vertical normalized distances
      in millimeters between the geometric centers of the glenoid fossa and the condyle
      and 2) calculating the anteroposterior joint space ratio. RESULTS: Using the
      first method, the horizontal distance between the centers of the condyle and the
      glenoid fossa was 14.0 +/- 11.1 in the ADD group and 5.3 +/- 10.9 in the control
      group (P <.001). The vertical distance was 64.7 +/- 22.7 in the ADD group and
      68.3 +/- 32.9 in the control group (P =.015). The ratio of the horizontal and the
      vertical condylar displacement in the ADD group was 2.4. Using the second method,
      the anteroposterior joint space ratios in the ADD group and in the control group
      were 1.7 +/- 0.5 and 1.2 +/- 0.4, respectively (P =.001). CONCLUSION: This study
      found that condyles of patients with ADD were situated more posterior and
      superior in the fossa than those in the control group. Moreover, in the ADD
      group, the posterior condylar displacement was noted to be 2.4 times greater than
      the superior condylar displacement.

PMID- 14699548
TI  - Effects of transitory lingual nerve impairment on speech: an acoustic study of
      diphthong sounds.
AB  - PURPOSE: The effects of lingual nerve impairment on the phonetic quality of
      diphthongs were studied by analyzing changes in their main acoustic features when
      anesthetic was injected into the lingual nerve to partly block the normal neural
      feedback mechanisms in speech. PATIENTS AND METHODS: The speech material
      consisted of 8 diphthongs in word context produced by 7 male speakers. Every
      utterance was repeated 10 times using normal speech rate and intonation with and
      without the anesthesia (Ultracain D-Suprarenin, 0.8 mL; Aventis Pharma Deutscland
      GmpH, Frankfurt am Main, Germany). In addition, 1 male speaker with permanent
      nerve impairment was studied. The acoustic features (F1, F2, F0, and duration)
      were analyzed using Computerized Speech Laboratory (CSL 4300B; Kay Elemetrics,
      Lincoln Park, NJ). RESULTS: At the group level, no general significant acoustic
      changes were found between the 2 conditions. The changes were highly individual
      and variable across the subjects. Significant changes were observed for all the
      subjects, most prominently for the subject with permanent nerve impairment.
      CONCLUSIONS: According to the results, lingual nerve impairment has effects on
      the production of diphthongs. A comparison between monophthongs and diphthongs
      showed that the alterations are more significant for the diphthongs than for
      other vowels indicating the more demanding, complicated, and complex manner of
      articulation of diphthongs.

PMID- 14699549
TI  - Patient-controlled sedation with propofol in minor oral surgery.
AB  - PURPOSE: We sought to evaluate the benefits of patient-controlled sedation with
      propofol for minor oral surgery. PATIENTS AND METHODS: After instructions were
      given on how to use the technique, 28 male and 24 female patients sedated
      themselves during minor oral surgery with titrating 18-mg bolus doses of propofol
      with a lockout period of 1 minute. RESULTS: Surgery lasted from 5 to 29 minutes;
      28 patients were moderately and 17 were deeply sedated. Seven patients were
      oversedated. All of those who were oversedated responded to commands within 1
      minute of being unresponsive and continued to obtain increments of propofol.
      Vital signs were stable in all patients even during oversedation. Eighteen
      patients were talkative, and 17 complained of pain along the vein. Operating
      conditions were good in 38, fair in 12, and poor in 2. The majority, 48 patients,
      were relaxed, and 47 were willing to undergo the sedation technique again. Ten
      had total, 22 had partial, and 20 had no amnesia. CONCLUSIONS: Relaxed patients,
      good operating conditions, and quick recovery of oversedated patients without
      unstable vital signs provide evidence that propofol has favorable pharmacokinetic
      and pharmacodynamic properties for patient-controlled sedation. This study also
      highlights the importance of close monitoring of patients during patient
      controlled sedation.

PMID- 14699550
TI  - Comparative study of the effect of a tube drain in impacted lower third molar
      surgery.
AB  - PURPOSE: Postoperative variables such as pain, swelling, and trismus after
      surgery of the impacted lower third molars are the main concerns of dental
      clinicians and surgeons. Many authors claim that the use of a drain could help
      control these variables. The purpose of this study was to evaluate the effect of
      the use of a tube drain in impacted lower third molar surgery. MATERIALS AND
      METHODS: Fifty-three patients of both genders with bilateral impacted lower third
      molars comprised our comparative study. The patients were divided into 2 groups:
      in the first the suture procedure was accomplished using a drain, and in the
      second the suture procedure was accomplished without a drain. The postoperative
      pain, swelling, and trismus were evaluated at 24 hours, 72 hours, 7 days, and 15
      days. RESULTS: In the group in which the drain was used, the control of the
      swelling variable was statistically significant at 24 and 72 hours (P <.001) in
      comparison with the group in which the drain was not used. However, pain and
      trismus were not statistically significant at the evaluation period. CONCLUSION:
      The use of the drain helps to control swelling. However, it had no effect on pain
      or trismus.

PMID- 14699551
TI  - Massachusetts General Hospital/Harvard Medical School MD oral and maxillofacial
      surgery program: a 30-year review.
AB  - PURPOSE: The first resident enrolled in the Massachusetts General
      Hospital/Harvard MD Oral and Maxillofacial Surgery (MD/OMFS) program graduated
      from Harvard Medical School (HMS) in 1972. The purpose of this report is to
      provide a summary of the first 30 years of the program and to outline plans for
      its future. MATERIALS AND METHODS: This was a retrospective cohort study and the
      sample was composed of the residents enrolled in the MD/OMFS program between 1971
      and 2000. Study variables included the dental school from which the resident
      graduated, successful completion of the MD/OMFS program, performance on parts I
      and II of the United States Medical Licensing Examination/National Board of
      Medical Examinations (USMLE/NBME), HMS grades, and career trajectories (full- or
      part-time academic or private practice). Appropriate descriptive and bivariate
      statistics were computed for all study variables. RESULTS: During the study
      interval, 56 residents entered the MD/OMFS program and graduated from HMS. All
      members of the cohort, regardless of the dental school from which they graduated,
      performed well as evidenced by USMLE/NBME scores and medical school grades.
      Ninety-four percent of eligible graduates have completed the American Board of
      Oral and Maxillofacial Surgery examination. The pass rate was 100%. Thirty-four
      graduates are involved in full- or part-time academic practice. Four trainees
      completed medical school but did not complete the OMFS program. CONCLUSION: The
      overwhelming majority of trainees completed the program, became board certified,
      and currently practice OMFS or a related specialty. A disproportionate number
      entered academic careers.

PMID- 14699552
TI  - Healing of maxillary alveolus in transport distraction osteogenesis for partial
      maxillectomy.
AB  - PURPOSE: This study aims to evaluate histologic healing of the new bone and soft
      tissue in the distraction gap of maxillary alveolus after transport distraction
      at different consolidation intervals. MATERIALS AND METHODS: In a monkey model,
      dentoalveolar segment was distracted backward to a surgical defect in the
      posterior maxilla with an internal distractor at a rate of 1 mm/day for 2 weeks.
      The distracted dentoalveolar processes were harvested at 1, 2, and 3 months of
      consolidation after the completion of distraction. Histologic examination
      included the new bone, gingiva of the distraction gap, and teeth carrying the
      transport segments. Tartrate-resistant acid phosphatase was used to assess the
      presence of osteoclasts in the new bone. The collagen type and expression of bone
      morphogenetic proteins (BMPs) in the new bone were assessed by
      immunohistochemistry. RESULTS: The histology confirmed new bone bridging the
      distraction gap at 1 month of consolidation. Woven bone was progressively
      replaced by mature lamellar bone at the second and third months. The gingiva
      covering the distraction gap was of normal appearance. There were no pathologic
      pulpal changes noted in the transport segment. Tartrate-resistant acid
      phosphatase-positive osteoclasts were minimal in the new bone. The mode of
      ossification was confirmed as intramembranous, and the fibrous stroma consisted
      mainly of collagen type I. At 1 month of consolidation, the BMPs were expressed
      profusely in the fibrous matrix and also inside the fibroblasts and osteoblasts.
      At 2 and 3 months of consolidation, the BMP expression intensity was reduced
      significantly in the fibrous stroma. CONCLUSIONS: The study confirmed that the
      bone regenerate in maxillary transport distraction was formed by intramembranous
      ossification and teeth in the transport segment remain viable after maxillary
      transport distraction osteogenesis.

PMID- 14699553
TI  - Accelerating effects of basic fibroblast growth factor on wound healing of rat
      palatal mucosa.
AB  - PURPOSE: In this study, basic fibroblast growth factor (bFGF) was examined for
      its ability to accelerate tissue repair in a rat oral mucosal wound. MATERIALS
      AND METHODS: A 4-mm mucosal defect was surgically made to the depth of the
      periosteum in a rat palate. bFGF was injected along the edge of the mucosal
      defect immediately after surgery. A control group received only phosphate
      buffered saline vehicle. RESULTS: bFGF significantly accelerated granular tissue
      formation and reepithelialization. From the histologic analysis, the bFGF-treated
      group showed relatively faster collagen maturation. Starting 3 days after
      surgery, fibroblast growth factor receptor 1 (FGFR1)-positive cells appeared in
      the granular and spinous cell layers of the reepithelializing mucosa in the bFGF
      treated group, whereas almost none was observed in the intact oral mucosa. By day
      5, FGFR1-positive cells were seen below the stratum corneum, even in the control
      group. However, the number and intensity of FGFR1-positive cells in the bFGF
      treated group were greater than in the control group. Results of immunostaining
      against proliferating cell nuclear antigen showed that bFGF stimulated cell
      proliferation of the basal cell layer in the regenerating epithelium. At a higher
      dose of bFGF, proliferating cell nuclear antigen-positive cells were also
      observed in the submucosal connective tissue. CONCLUSION: By the induction of its
      ligand protein concomitant with direct effects such as increased granular tissue
      formation and reepithelialization, a single topical application of bFGF
      facilitated wound healing in rat oral mucosa. The results of this study support
      the consideration for bFGF application for patients with impaired healing of oral
      mucosal injury.

PMID- 14699554
TI  - Sarcoma of mandible.

PMID- 14699555
TI  - Management of the obese patient undergoing office-based oral and maxillofacial
      surgery procedures.

PMID- 14699556
TI  - Cervical tuberculosis (scrofula): a case report.

PMID- 14699557
TI  - Temporomandibular joint osteoarthritis: a cause of a serous otitis media? A case
      report.

PMID- 14699558
TI  - Excessive hemorrhage after dental extractions using low-molecular-weight heparin
      (Lovenox) anticoagulation therapy.

PMID- 14699559
TI  - The tubed walking radial forearm flap for salvaging the flap- and vessel-depleted
      head and neck cancer patient.

PMID- 14699560
TI  - Gas phenomenon in the superior space of the temporomandibular joint: report of a
      case.

PMID- 14699561
TI  - A modified leverage technique to simplify the Le Fort I downfracture.

PMID- 14699572
TI  - James A. Weston and the JAWsfest: a celebration of his contributions to our
      understanding of the neural crest.

PMID- 14699573
TI  - Significance of the cranial neural crest.
AB  - The cranial neural crest has long been viewed as being of particular
      significance. First, it has been held that the cranial neural crest has a
      morphogenetic role, acting to coordinate the development of the pharyngeal
      arches. By contrast, the trunk crest seems to play a more subservient role in
      terms of embryonic patterning. Second, the cranial crest not only generates
      neurons, glia, and melanocytes, but additionally forms skeletal derivatives
      (bones, cartilage, and teeth, as well as smooth muscle and connective tissue),
      and this potential was thought to be a unique feature of the cranial crest.
      Recently, however, several studies have suggested that the cranial neural crest
      may not be so influential in terms of patterning, nor so exceptional in the
      derivatives that it makes. It is now becoming clear that the morphogenesis of the
      pharyngeal arches is largely driven by the pharyngeal endoderm. Furthermore, it
      is now apparent that trunk neural crest cells have skeletal potential. However,
      it has now been demonstrated that a key role for the cranial neural crest streams
      is to organise the innervation of the hindbrain by the cranial sensory ganglia.
      Thus, in the past few years, our views of the significance of the cranial neural
      crest for head development have been altered. Developmental Dynamics 229:5-13,
      2004.

PMID- 14699574
TI  - Comparative analysis of neural crest cell death, migration, and function during
      vertebrate embryogenesis.
AB  - Cranial neural crest cells are a multipotent, migratory population that generates
      most of the cartilage, bone, connective tissue and peripheral nervous system in
      the vertebrate head. Proper neural crest cell patterning is essential for normal
      craniofacial morphogenesis and is highly conserved among vertebrates. Neural
      crest cell patterning is intimately connected to the early segmentation of the
      neural tube, such that neural crest cells migrate in discrete segregated streams.
      Recent advances in live embryo imaging have begun to reveal the complex behaviour
      of neural crest cells which involve intricate cell-cell and cell-environment
      interactions. Despite the overall similarity in neural crest cell migration
      between distinct vertebrates species there are important mechanistic differences.
      Apoptosis for example, is important for neural crest cell patterning in chick
      embryos but not in mouse, frog or fish embryos. In this paper we highlight the
      potential evolutionary significance of such interspecies differences in jaw
      development and evolution. Developmental Dynamics 229:14-29, 2004.

PMID- 14699575
TI  - Slow degeneration of zebrafish Rohon-Beard neurons during programmed cell death.
AB  - Rohon-Beard cells are large, mechanosensory neurons located in the dorsal spinal
      cord of anamniote vertebrates. In most species studied to date, these cells die
      during development. We followed labeled Rohon-Beard cells in living zebrafish
      embryos and found that they degenerate slowly, over many days. During
      degeneration, the soma shrinks and finally disappears, and the processes become
      beady in appearance and finally break apart, but they do not retract. Zebrafish
      Rohon-Beard cells apparently fragment their DNA, as revealed by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling,
      before undergoing degenerative morphologic changes. We also followed the
      development of labeled dorsal root ganglion neurons, as they are developing at
      the same stages that Rohon-Beard cells are degenerating. We found that, although
      axons of both cell types extend into similar regions, Rohon-Beard cells
      degenerate normally in mutants lacking dorsal root ganglia, providing evidence
      that interactions between the two cell types are not responsible for Rohon-Beard
      cell degeneration. Developmental Dynamics 229:30-41,2004.

PMID- 14699576
TI  - MMP-2 plays an essential role in producing epithelial-mesenchymal transformations
      in the avian embryo.
AB  - To investigate the roles that matrix-degrading proteases may have in development
      of the chicken embryo, we documented the expression pattern of matrix
      metalloprotease-2 (MMP-2, 72-kDa type IV collagenase or gelatinase A) and
      perturbed its function in vitro and in vivo. MMP-2 is expressed as neural crest
      cells detach from the neural epithelium during an epithelial-mesenchymal
      transformation (EMT) but is rapidly extinguished as they disperse. It is also
      expressed in the sclerotome and in the dermis at the time that the EMT is
      initiated, and also as these cells migrate, and is down-regulated once motility
      has ceased. These patterns suggest that MMP-2 plays a role in cell motility
      during the EMT and during later morphogenesis. Inhibitors of MMPs, including BB
      94 and TIMP-2 (tissue inhibitor of metalloprotease-2), prevent the EMT that
      generates neural crest cells, both in tissue culture and in vivo, but do not
      affect migration of the cells that have already detached from the neural tube.
      Similarly, knockdown of MMP-2 expression in the dorsal neural tube using
      antisense morpholino oligos perturbs the EMT, but also does not affect migration
      of neural crest cells after they have detached from the neural tube. On the other
      hand, when somites in culture are treated with TIMP-2, some mesenchymal cells are
      produced, suggesting that they undergo the EMT, but show greatly reduced
      migration through the collagen gel. MMP-2 is also expressed in mesenchyme where
      tissue remodeling is in progress, such as in the developing feather germs, in the
      head mesenchyme, in the lateral plate mesoderm, and in the limb dermis,
      especially in the regions where tendons are developing. Comparisons of these
      expression patterns in multiple embryonic tissues suggest a probable role for MMP
      2 in the migration phase of the EMT, in addition to mesenchyme dispersion and
      tissue remodeling. Developmental Dynamics 229:42-53, 2004.

PMID- 14699577
TI  - Complementation of melanocyte development in SOX10 mutant neural crest using
      lineage-directed gene transfer.
AB  - An in vitro gene complementation approach has been developed to dissect gene
      function and regulation in neural crest (NC) development and disease. The
      approach uses the avian RCAS virus to express genes in NC cells derived from
      transgenic mice expressing the RCAS receptor TVA, under the control of defined
      promoter elements. Constructs for creating TVA transgenic mice were developed
      using site-specific recombination GATEWAY (GW), compatible vectors that can also
      be used to facilitate analysis of genomic fragments for transcriptional
      regulatory elements. By using these GW vectors to facilitate cloning, transgenic
      mouse lines were generated that express TVA in SOX10-expressing NC stem cells
      under the control of the Pax3 promoter. The Pax3-tv-a transgene was bred onto a
      Sox10-deficient background, and the feasibility of complementing genetic NC
      defects was demonstrated by infecting the Pax3-tv-a cells with an RCAS-Sox10
      expression virus, thereby rescuing melanocyte development of Sox10-deficient NC
      cells. This system will be useful for assessing genetic hierarchies in NC
      development. Developmental Dynamics 229:54-62, 2004.

PMID- 14699578
TI  - Homocysteine inhibits cardiac neural crest cell formation and morphogenesis in
      vivo.
AB  - Elevated homocysteine increases the risk of neurocristopathies. Here, we
      determined whether elevating homocysteine altered the proliferation or number of
      chick neural crest cells that form between the midotic and third somite in vivo.
      Homocysteine increased the number of neural tube cells but decreased neural crest
      cell number. However, the sum total of cells was not different from controls. In
      controls, the 5-bromo-2'-deoxyuridine-labeling index was higher in newly formed
      neural crest cells than in their progenitors, paralleling reports showing these
      progenitors must pass the restriction point before undergoing epithelial
      mesenchymal transition. Homocysteine decreased the labeling index of newly formed
      neural crest cells, suggesting that it inhibited cell cycle progression of neural
      crest progenitors or the S-phase entry of newly formed neural crest cells.
      Homocysteine also inhibited neural crest dispersal and decreased the distance
      they migrated from the neural tube. These results show neural crest morphogenesis
      is directly altered by elevated homocysteine in vivo. Developmental Dynamics
      229:63-73, 2004.

PMID- 14699579
TI  - Multiple roles of Sox2, an HMG-box transcription factor in avian neural crest
      development.
AB  - Expression of Sox2, which encodes an HMG-box-type transcription factor, is down
      regulated in the neural plate when neural crest segregates from dorsal neural
      tube and remains low during crest cell migration. Sox2 expression is subsequently
      up-regulated in some crest-derived cells in the developing peripheral nervous
      system and is later restricted to glial sublineages. Misexpression of Sox2 and
      mutant forms of Sox2 both in neural plate explants and in embryonic ectoderm
      reveals that Sox2 inhibits neural crest formation as a transcriptional activator.
      Similar manipulation of Sox2 function in migratory and postmigratory neural crest
      derived cells indicates that Sox2 regulates proliferation and differentiation in
      developing peripheral nervous system. Developmental Dynamics 229:74-86, 2004.

PMID- 14699580
TI  - Skeletal and pigment cell defects in the lockjaw mutant reveal multiple roles for
      zebrafish tfap2a in neural crest development.
AB  - Members of the AP-2 transcription factor family have critical roles in many
      aspects of embryonic development. The zebrafish tfap2a mutant lockjaw (low)
      displays defects in skeletal and pigment cell derivatives of the neural crest.
      Here we show essential roles for tfap2a in subsets of embryonic cartilages and
      pigment cells. Defects in cartilage of the hyoid arch in low correlate with a
      loss of Hox group 2 gene expression and are suggestive of a transformation to a
      mandibular fate. In contrast, loss of joints in the mandibular arch and defects
      in certain types of pigment cells suggest a requirement for tfap2a independent of
      Hox regulation. Early melanophores do not develop in low mutants, and we propose
      that this results in part from a loss of kit function, leading to defects in
      migration, as well as kit-independent defects in melanophore specification.
      Iridophores are also reduced in low, in contrast to xanthophores, revealing a
      role for tfap2a in the development of pigment subpopulations. We propose a model
      of tfap2a function in the neural crest in which there are independent functions
      for tfap2a in specification of subpopulations of pigment cells and segmental
      patterning of the pharyngeal skeleton through the regulation of Hox genes.
      Developmental Dynamics 229:87-98, 2004.

PMID- 14699581
TI  - Long-distance cue from emerging dermis stimulates neural crest melanoblast
      migration.
AB  - Neural crest melanoblasts display unique navigational abilities enabling them to
      colonize the dorsal path between ectoderm and somite. One signal shown here to
      elicit melanoblast migration is a chemotactic cue supplied by the emerging
      dermis. Until dermis emerges, melanoblasts fail to enter the dorsal path. The
      dermis emerges from a site that is too distant to stimulate migration by cell
      contact. Instead, surgeries show that dermis elicits migration from a distance.
      When dermis is grafted distally, neural crest cells enter the path precociously.
      Moreover, large grafts recruit melanoblasts from the control sides (without
      increasing crest cell numbers) as well as a few crest cells from ventral somite.
      Because other grafted tissues fail to stimulate migration, the dermis stimulus is
      specific. This report is the first documentation that trunk neural crest cells
      can be guided chemotactically. It also extends evidence that migration is
      exquisitely sensitive to temporal-spatial patterns of somite morphogenesis.
      Developmental Dynamics 229:99-108, 2004.

PMID- 14699582
TI  - Identification of neural crest competence territory: role of Wnt signaling.
AB  - In recent years, research on neural crest induction has allowed the
      identification of several molecules as candidates for neural crest inducers.
      Although many of these molecules have the ability to induce neural crest in
      different assays, a general mechanism of neural crest induction that includes a
      description of the tissues that produce the inductive signals and the time and
      steps in which this process takes place remains elusive. To better understand the
      mechanism of neural crest induction, we developed an assay that has been used
      previously by Nieuwkoop to study anterior-posterior pattern of the neural plate.
      Folds of competent ectoderm were implanted in different positions of a young
      neurula embryo, and the induction of neural crest was analyzed using the
      expression of the neural crest marker Xslug. We identified a very localized
      region of the early neurula where it is possible to get neural crest induction,
      whereas all of the regions tested showed a clear induction of the neural plate
      marker Xsox2. These results indicate that there is a region in the embryo with
      the appropriate combination of signals needed to induce neural crest cells; we
      called this region the neural crest competence territory. In addition, our
      results show that neural crest induction is always accompanied by neural plate
      induction, but there are many cases where neural plate was induced without neural
      crest. These results support the model in which the neural crest is induced by an
      interaction between neural plate and epidermis, but they also suggest that
      additional signals are required. By making grafts of different sizes and
      implanting them in the epidermis or the neural plate, we concluded that one of
      the inductive signals is produced in the dorsal region of the embryo and travels
      into the ectoderm. Finally, by performing gain- and loss-of-function of Wnt
      signaling experiments, we show that this pathway plays an important role not only
      in neural crest induction but also in the specification of the neural crest
      competence territory. Developmental Dynamics 229:109-117, 2004.

PMID- 14699583
TI  - Neural crest and the origin of ectomesenchyme: neural fold heterogeneity suggests
      an alternative hypothesis.
AB  - The striking similarity between mesodermally derived fibroblasts and
      ectomesenchyme cells, which are thought to be derivatives of the neural crest,
      has long been a source of interest and controversy. In mice, the gene encoding
      the alpha subunit of the platelet-derived growth factor receptor (PDGFRalpha) is
      expressed both by mesodermally derived mesenchymal cells and by ectomesenchyme.
      Whole-mount immunostaining previously revealed that PDGFRalpha is present in the
      cephalic neural fold epithelium of early murine embryos (Takakura et al. [1997] J
      Histochem Cytochem 45:883-893). We now show that, within the neural fold, a sharp
      boundary exists between E-cadherin-expressing non-neural epithelium and the
      neural epithelium of the dorsal ridge. In addition, we found that cells
      coexpressing E-cadherin and PDGFRalpha are present in the non-neural epithelium
      of the neural folds. These observations raise the possibility that at least some
      PDGFRalpha(+) ectomesenchyme originates from the lateral non-neural domain of
      neural fold epithelium. This inference is consistent with previous reports
      (Nichols [ 1981] J Embryol Exp Morphol 64:105-120; Nichols [ 1986] Am J Anat
      176:221-231) that mesenchymal cells emerge precociously from an epithelial neural
      fold domain resembling the primitive streak in the early embryonic epiblast.
      Therefore, we propose the name "metablast" for this non-neural epithelial domain
      to indicate that it is the site of a delayed local delamination of mesenchyme
      similar to involution of mesoderm during gastrulation. We further propose the
      testable hypothesis that neural crest and ectomesenchyme are developmentally
      distinct progenitor populations and that at least some ectomesenchyme is
      metablast-derived rather than neural crest-derived tissue. Developmental Dynamics
      229:118-130, 2004.

PMID- 14699584
TI  - Traf6 is essential for murine tooth cusp morphogenesis.
AB  - Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in
      patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been
      established that mutations in the tumor necrosis factor (TNF) superfamily of
      molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated
      death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for
      several forms of HED in humans and mice. We show here by in situ hybridisation
      that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha,
      TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel
      knot signalling centres that are believe to regulate cuspal morphogenesis during
      murine tooth development. Traf6 is known to function as an intracellular adaptor
      protein for Troy and examination of Traf6 mutant mice revealed abnormalities in
      molar teeth that are similar but more severe than those produced by mutations in
      Eda signalling molecules. This finding suggests that, in additional to
      ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar
      tooth cusp formation and identifies an essential role for a Traf in tooth
      development. Developmental Dynamics 229:131-135, 2004.

PMID- 14699585
TI  - Relative expression of Slug, RhoB, and HNK-1 in the cranial neural crest of the
      early chicken embryo.
AB  - The neural crest constitutes a complex population of cells that originates at the
      edges of the neural plate of vertebrate embryos and gives rise to a high
      diversity of tissues and cell types. Molecular markers are very useful to
      identify cell populations, and in the case of the neural crest at early stages,
      many of them have been described. Here, we show a series of chicken embryos
      double labeled for several of the most commonly used crest markers that evidence
      the existence of different subpopulations. Slug is a very good marker for
      premigratory and early migratory cranial neural crest, RhoB labels delaminating
      cells and the very early migratory population, and the HNK-1 epitope is acquired
      in the migratory crest cells at a distance from the neural tube, with a
      significant proportion of the Slug-expressing migratory cells negative for HNK-1.
      The existence of these crest subpopulations should be considered when analyzing
      both wild-type embryos and the phenotype of experimentally manipulated chick
      embryos. Developmental Dynamics 229:136-139, 2004.

PMID- 14699586
TI  - Neural crest as a way of knowing: new perspectives on lineage and morphogenesis.

PMID- 14699588
TI  - Signal integration during development: insights from the Drosophila eye.
AB  - The Drosophila eye is a highly ordered epithelial tissue composed of
      approximately 750 subunits called ommatidia arranged in a reiterated hexagonal
      pattern. At higher resolution, observation of the constituent photoreceptors,
      cone cells, and pigment cells of the eye reveals a highly ordered mosaic of
      amazing regularity. This relatively simple organization belies the repeated
      requirement for spatially and temporally coordinated inputs from the Hedgehog
      (Hh), Wingless (Wg), Decapentaplegic (Dpp), JAK-STAT, Notch, and receptor
      tyrosine kinase (RTK) signaling pathways. This review will discuss how signaling
      inputs from the Notch and RTK pathways, superimposed on the developmental history
      of a cell, facilitate context-specific and appropriate cell fate specification
      decisions in the developing fly eye. Lessons learned from investigating the
      combinatorial signal integration strategies underlying Drosophila eye development
      will likely reveal cell-cell communication paradigms relevant to many aspects of
      invertebrate and mammalian development. Developmental Dynamics 229:162-175, 2004.

PMID- 14699587
TI  - Turning heads: development of vertebrate branchiomotor neurons.
AB  - The cranial motor neurons innervate muscles that control eye, jaw, and facial
      movements of the vertebrate head and parasympathetic neurons that innervate
      certain glands and organs. These efferent neurons develop at characteristic
      locations in the brainstem, and their axons exit the neural tube in well-defined
      trajectories to innervate target tissues. This review is focused on a subset of
      cranial motor neurons called the branchiomotor neurons, which innervate muscles
      derived from the branchial (pharyngeal) arches. First, the organization of the
      branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared,
      and the underlying axon guidance mechanisms will be addressed. Next, the
      molecular mechanisms that generate branchiomotor neurons and specify their
      identities will be discussed. Finally, the caudally directed or tangential
      migration of facial branchiomotor neurons will be examined. Given the advances in
      the characterization and analysis of vertebrate genomes, we can expect rapid
      progress in elucidating the cellular and molecular mechanisms underlying the
      development of these vital neuronal networks. Developmental Dynamics 229:143-161,
      2004.

PMID- 14699589
TI  - Gene regulatory factors in pancreatic development.
AB  - The intensity of research on pancreatic development has increased markedly in the
      past 5 years, primarily for two reasons: we now know that the insulin-producing
      beta-cells normally arise from an endodermally derived, pancreas-specified
      precursor cell, and successful transplants of islet cells have been performed,
      relieving patients with type I diabetes of symptoms for extended periods after
      transplantation. Combining in vitro beta-cell formation from a pancreatic biopsy
      of a diabetic patient or from other stem-cell sources followed by endocrine cell
      transplantation may be the most beneficial route for a future diabetes therapy.
      However, to achieve this, a thorough understanding of the genetic components
      regulating the development of beta-cells is required. The following review
      discusses our current understanding of the transcription factor networks
      necessary for pancreatic development and how several genetic interactions coming
      into play at the earliest stages of endodermal development gradually help to
      build the pancreatic organ. Developmental Dynamics 229:176-200, 2004.

PMID- 14699591
TI  - Efficacy and safety of DALI LDL-apheresis at high blood flow rates: a prospective
      multicenter study.
AB  - Direct adsorption of lipids (DALI) is the first LDL-apheresis method compatible
      with whole blood. Usually, the blood flow rate is adjusted at 60-80 ml/min, which
      results in session times of about 2 hr. The present study was performed to test
      the safety and efficacy of low-density lipoprotein cholesterol (LDL-C) and
      lipoprotein (a) [Lp(a)] removal by DALI at high blood flow rates in order to
      reduce treatment time. Thirteen chronic DALI patients in seven centers suffering
      from hypercholesterolemia (LDL-C 162 +/- 42 mg/dl at baseline) and coronary
      artery disease were treated on a weekly or biweekly basis by DALI apheresis. The
      blood flow rate QB was held constant for at least two sessions, respectively, and
      was increased from 60 to 80, 120, 160, 200, and 240 ml/min. All patients had pre
      existing av-fistulas. The anticoagulation was performed by a heparin bolus plus
      ACD-A at a ratio of citrate:blood ranging from 1:20 to 1:90. Clinically, the
      sessions were well tolerated and only 26/201 sessions (12%) of the treatments
      were fraught with minor adverse events. Acute LDL-C reductions (derived from LDL
      C levels determined by lipoprotein electrophoresis) averaged 72/66/60/53/50/48%
      for QB=60/80/120/160/200/240 ml/min. Lp(a) reductions were 68/67/62/60/58/56%,
      whereas HDL-C losses were < or =10%. Routine blood chemistries and blood cell
      counts remained in the normal range. Treatment times averaged 142/83/45 min at
      Qb=60/120/240 ml/min. On average, DALI LDL-apheresis could be performed safely
      and effectively at high blood flow rates up to at least 120 ml/min in patients
      with good blood access, which significantly reduced treatment time from 142 to 83
      min (-42%).

PMID- 14699592
TI  - Extracorporeal double filtration plasmapheresis in acute atherothrombotic brain
      infarction caused by major artery occlusive lesion.
AB  - Extracorporeal double filtration plasmapheresis (EDFP) can quickly lower plasma
      viscosity and fibrinogen concentration. EDFP has the potential to improve
      cerebral microcirculation in acute ischemic stroke and ultimately to salvage
      penumbral tissue. However, no evidence is available to show that EDFP can
      increase cerebra blood flow (CBF). Therefore, we investigated whether EDFP could
      increase CBF by quantitative CBF measurements and documented the clinical effects
      of EDFP in acute ischemic stroke. EDFP was performed ten times in seven patients
      diagnosed as having acute atherothrombotic brain infarction caused by major
      artery occlusive lesion. They also fulfilled one of the following entry criteria:
      1) diffusion/perfusion mismatch demonstrated by MRI on admission; 2) a
      hemispheric syndrome, but only a small lesion on diffusion weighted MRI (<25% of
      MCA territory); or 3) progressing stroke. Exclusion criteria were 1)
      contraindication of heparin or 2) spontaneous improvement of symptoms. Time from
      stroke onset to EDFP varied from 5 hr to 7 days. Plasma viscosity was quickly
      lowered by EDFP without affecting RBC counts, Hb, or Hct in all patients.
      Positron emission tomography (PET) with 15-O labeled H2O measurements revealed a
      significant CBF increase from 36.4 +/- 8.3 ml/100 g/min to 40.7 +/- 6.8 ml/100
      g/min in the affected hemisphere (P=0.048). Definite CBF improvement was also
      demonstrated by single photon emission computed tomography (SPECT) in one of two
      patients who had severe stenosis of the middle cerebral artery. Furthermore, this
      patient showed remarkable improvement of hemiplegia immediately following EDFP
      (NIHSS score: 18 to 13). In conclusion, EDFP can increase CBF in ischemic brain
      tissue in acute atherothrombotic brain infarction. Further clinical studies
      should focus on the efficacy of EDFP on outcome of patients with this stroke
      subtype.

PMID- 14699590
TI  - T-box genes in early embryogenesis.
AB  - The T-box gene family, encoding related DNA-binding transcriptional regulators,
      plays an essential role in controlling many aspects of embryogenesis in a wide
      variety of organisms. The T-box genes exhibit diverse patterns of spatial and
      temporal expression in the developing embryo, and both genetic and molecular
      embryological studies have demonstrated their importance in regulating cell fate
      decisions that establish the early body plan, and in later processes underlying
      organogenesis. Despite these studies, little is known of either the regulation of
      the T-box genes or the identities of their transcriptional targets. The aim of
      this review is to examine the diverse yet conserved roles of several T-box genes
      in regulating early patterning in chordates and to discuss possible mechanisms
      through which this functional diversity might arise. Developmental Dynamics
      229:201-218, 2004.

PMID- 14699593
TI  - Long-term prognosis for Guillain-Barre syndrome: evaluation of prognostic factors
      and clinical experience of automated double filtration plasmapheresis.
AB  - Sixty patients with Guillain-Barre syndrome (GBS), aged 16-83 years, have been
      identified over a period of 7 years. Of 60 patients, 30 received the double
      filtration plasmapheresis (DFP), 4 received intravenous immunoglobulin, and the
      other 26 received supportive care only. Therapeutic outcomes at 1 year were
      determined using a modified Barthel index. At a follow-up of 1 year or longer, 31
      patients (52%) had recovered, 24 (40%) had residua, and 5 (8%) had died.
      According to the statistical analysis, disability at the nadir and
      electrophysiological signs significantly influenced the long-term outcomes.
      Complications associated with DFP procedures included physiologic change,
      technique-related complications, and vascular access-related complications. None
      of our patients had fatal complications related to DFP treatment. Contrary to the
      established belief that the disease has a favorable outcome, several hospital
      treated patients may still die or present residua even several months after the
      onset of symptoms. Because disability at the nadir influences the outcomes, early
      diagnosis and choice of appropriate treatment, which might include DFP, to
      prevent further neurological deficits, are essential to maximize the potential
      for survival.

PMID- 14699594
TI  - Plasmapheresis for hyperlipidemic pancreatitis.
AB  - Patients with triglyceride levels over 1,000 mg/dl are at high risk of developing
      acute pancreatitis. This study aimed to determine the effectiveness of plasma
      exchange (PE) in reducing triglyceride levels during an acute attack of
      hyperlipidemic pancreatitis (HLP). A total of 17 hypertriglyceridemic patients
      with the complication of acute pancreatitis received one course of PE treatment
      for one or two consecutive sessions. The respective mean removal rates during a
      single PE for triglyceride, cholesterol, amylase, and lipase were 66.3, 62.1,
      70.0, and 84.8%, respectively. An additional one exchange increased the removal
      rate to 83.3, 66.2, 85.5, and 87.0%, respectively. For the two-sessions of
      treatment, the removal rates were higher for triglyceride (P=0.0015) and amylase
      with a borderline statistical significance (P=0.0641). Better triglyceride
      clearance correlated well with lower levels of transmembrane pressure (TMP) at 90
      minutes after PE (r2=0.5782, P=0.0010) and shorter plasmapheresis duration
      (r2=0.2241, P=0.0427). Thirteen of seventeen patients (76.5%) recovered
      completely, eight patients in a single-session, and five in two-sessions. Two
      patients developed intra-abdominal abscess, necessitating surgical drainage and
      two patients died due to both septic shock and multi-organ failure. No
      significant predictor of clinical outcome was identified. In summary, PE
      treatment is an effective method to clear lipids and enzymes from plasma in a
      single session for most HLP patients. A greater extraction of triglyceride would
      result in a reduced TMP and a shorter duration of PE treatment.

PMID- 14699595
TI  - Harvesting peripheral blood stem cells from healthy donors on 4th day of cytokine
      mobilization.
AB  - A pilot study was conducted to evaluate the efficacy of harvesting peripheral
      blood stem cells from normal healthy donors on day 4 after mobilization with G
      CSF at 10 microg/kg for 4 days or a sequential combination of GM-CSF at 10
      microg/kg for 2 days and G-CSF at 10 microg/kg for 2 more days. Harvesting over
      the target dose (>4 x 10(6) kg) of CD34+ cells based on the lst leukapheresis
      performed on day 4 was possible from 7 (53.8%) out of 13 donors. The 7 matched
      recipients all exhibited early engraftment, except for one who experienced
      transplant-related mortality, and no differences were observed with the
      recipients transplanted with stem cells harvested after a 5-6-day growth-factor
      (GF) treatment. Accordingly, harvesting from normal healthy donors on day 4 after
      mobilization treatment with a GF was found to be feasible for allogeneic
      peripheral blood stem cell transplantation and more economical in terms of the
      cost of the GF and the donor's commitment.

PMID- 14699596
TI  - Heat insoluble cryoglobulin associated with gangrene in multiple myeloma.
AB  - Cryoglobulins are immunoglobulins that have tendency to precipitate in
      temperatures below 37 degrees C and dissolve with rewarming. Monoclonal
      cryoglobulins are usually associated with a distinct hematological disorder and
      often are asymptomatic. Heat insoluble cryoglobulin has been described with
      Sjogren's syndrome and glomerulonephritis but, not with multiple myeloma. Severe
      sensitivity to cold occurs with high thermal insolubility of the cryoprotein,
      with dramatic symptoms when exposed to minimal lowering of the temperature. We
      report a case of a 49 year old man with multiple myeloma and an unusual type I
      cryoglobulin that caused occlusive gangrene. The cryoglobulin appeared as a milky
      white precipitate that was resistant to re-suspension and did not dissolve at 37
      degrees C. Immunoelectrophoresis of the cryoglobulin, which dissolved at 56
      degrees C, showed it to be composed of a monoclonal IgG kappa protein (3.5 g/dl).
      Unlike most high thermal insoluble cryoglobulin, cold associated symptoms were
      not seen. In addition to steroids, plasmapheresis was initiated thrice a week
      with albumin fluid replacement. Plasmapheresis caused a marked decline in
      cryocrit levels from 21% to less than 0.5% in 9 days after 4 procedures with
      resolution of the gangrene of the feet and after 6 treatments, vasculitic
      symptoms improved dramatically. The cryoglobulin test was negative 2 weeks after
      initiation of treatment. The patient was treated for the myeloma and there was no
      recurrence of occlusive symptoms. Proper laboratory procedure and careful
      examination and handling of cryoglobulinemic samples facilitate detection of
      unusual cryoglobulins. This is a unique report of multiple myeloma with gangrene
      of lower extremities that has a heat insoluble cryoglobulin.

PMID- 14699597
TI  - Extracorporeal removal of antimicrobials during plasmapheresis.

PMID- 14699600
TI  - Direct neural network application for automated cell recognition.
AB  - BACKGROUND: Automated cell recognition from histologic images is a very complex
      task. Traditionally, the image is segmented by some methods chosen to suit the
      image type, the objects are measured, and then a classifier is used to determine
      cell type from the object's measurements. Different classifiers have been used
      with reasonable success, including neural networks working with data from
      morphometric analysis. METHODS: Image data of cells were input directly into
      neural networks to determine the feasibility of direct classification by using
      pixel intensity information. Several types of neural network and their ability to
      work with cells in a complex patterned background were assessed for a variety of
      images and cell types and for the accuracy of classification. RESULTS:
      Inflammatory cells from animal biomaterial implants in rabbit paravertebral
      muscle were imaged in histologic sections. Simple, three-layer, fully connected,
      back-propagation neural networks and four-layer networks with two layers of a
      shared-weights neural network were most successful at classifying the cells from
      the images, with 97% and 98% correct recognition rates, respectively.
      CONCLUSIONS: The high accuracy recognition rate shows the potential for direct
      classification of visual image pixel data by neural networks.

PMID- 14699601
TI  - Fourier transformed spectral bio-imaging for studying the intracellular fate of
      liposomes.
AB  - BACKGROUND: To improve the efficiency of liposomal drug targeting systems, it is
      necessary to understand the mechanism of liposome uptake by the cell and to
      follow the intracellular fate of internalized liposomes and their contents.
      METHODS: We applied multiple-color fluorescence imaging spectroscopy, using a
      combination of five fluorescent dyes with a significant spectral overlap. pH
      sensitive liposomes were labeled with the hydrophilic dye fluorescein
      isothiocyanate-dextran (FITC-dextran) or the lipophilic membrane marker rhodamine
      B-phosphoethanolamine (Rh-PE) and incubated with COS-7 cells. Further, the cells
      were stained with specific markers: the cell membrane was fluorescently labeled
      with Vybrant DiO, lysosomes were stained with LysoTracker Red, and 4',6 diamidino
      2-phenylindole dihydrochloride was used for counterstaining the nucleus. RESULTS:
      All five dyes were used simultaneously and were spectrally distinguished by the
      system. FITC-dextran-labeled liposomes showed a distribution pattern different
      from identically composed liposomes labeled with Rh-PE: the highly lipophilic Rh
      PE was colocalized with the lysosomotropic dye LysoTracker Red, whereas liposomal
      FITC-dextran was not accompanied by LysoTracker Red in all cases. CONCLUSIONS:
      (a) Spectral (bio-) imaging is a powerful method for studying the intracellular
      fate of liposomal compounds. (b) We assume that the liposome membrane marker Rh
      PE influences the uptake of particles due to its surface-modifying properties. We
      propose that this head-group-labeled phospholipid acts as a ligand for cellular
      receptors and triggers receptor-mediated (clathrin-dependent) endocytosis.

PMID- 14699602
TI  - Image analysis for automatic segmentation of cytoplasms and classification of
      Rac1 activation.
AB  - BACKGROUND: Rac1 is a GTP-binding molecule involved in a wide range of cellular
      processes. Using digital image analysis, agonist-induced translocation of green
      fluorescent protein (GFP) Rac1 to the cellular membrane can be estimated
      quantitatively for individual cells. METHODS: A fully automatic image analysis
      method for cell segmentation, feature extraction, and classification of cells
      according to their activation, i.e., GFP-Rac1 translocation and ruffle formation
      at stimuli, is described. Based on training data produced by visual annotation of
      four image series, a statistical classifier was created. RESULTS: The results of
      the automatic classification were compared with results from visual inspection of
      the same time sequences. The automatic classification differed from the visual
      classification at about the same level as visual classifications performed by two
      different skilled professionals differed from each other. Classification of a
      second image set, consisting of seven image series with different concentrations
      of agonist, showed that the classifier could detect an increased proportion of
      activated cells at increased agonist concentration. CONCLUSIONS: Intracellular
      activities, such as ruffle formation, can be quantified by fully automatic image
      analysis, with an accuracy comparable to that achieved by visual inspection. This
      analysis can be done at a speed of hundreds of cells per second and without the
      subjectivity introduced by manual judgments.

PMID- 14699603
TI  - Double staining of Plasmodium falciparum nucleic acids with hydroethidine and
      thiazole orange for cell cycle stage analysis by flow cytometry.
AB  - BACKGROUND: Microarray analyses of stage-specific gene expression of Plasmodium
      falciparum require purification of RNAs from highly synchronized cultures. To
      date, no reliable method to control the quality of synchronization of P.
      falciparum cultures is available. METHODS: A double-staining method using
      hydroethidine and thiazole orange for nucleic acid staining was carried out to
      compare by flow cytometric analysis the nucleic acid labeling of synchronized P.
      falciparum in cultures at different time points of the 48-h intraerythrocytic
      cycle. RESULTS: With this method, we determined the quality of culture
      synchronization in schizont and ring stages. Nucleic acid analysis, based on
      thiazole orange fluorescence, clearly showed that low levels of schizonts in ring
      cultures results in a high contamination of ring nucleic acids by schizonts.
      Conversely, nucleic acids from trophozoite or schizont cultures containing ring
      stages did not present a significant contamination by ring nucleic acids.
      CONCLUSION: The results demonstrated a very low nucleic acid content in the ring
      stage when compared with the high nucleic acid content of schizont-stage
      parasites. The rapid and reliable flow cytometric strategy using hydroethidine-
      and thiazole orange-stained parasite nucleic acids allows monitoring of the
      purity of the preparation, thus greatly improving the quality assessment of
      parasite cultures, a critical step to study gene expression patterns.

PMID- 14699604
TI  - Hollow-fiber assay for ligand-mediated cell adhesion.
AB  - BACKGROUND: The investigation of receptor-ligand interactions in the cellular
      context presents significant technical challenges, first, to immobilize the
      ligand in a manner that preserves functional properties and, second, to relate
      ligand properties to cell adhesion and other cellular processes. METHODS: Ligand
      mediated cell adhesion was characterized by the development of a cellulose hollow
      fiber adhesion assay in which ligand (protein A) was immobilized onto the
      cellulose membrane as a recombinant fusion protein containing a cellulose-binding
      domain affinity tag. Modules containing single cellulose hollow fibers were
      connected to a micro-flow system for cell deposition and detachment with fluid
      shear stress. The cell adhesion process that occurred inside a segment of hollow
      fiber was observed in real time by using an inverted microscope equipped with a
      CCD camera and digital frame grabber. Image analysis software was developed to
      count cells and record digital images. RESULTS: Cell adhesion strength was
      characterized by counting the number of cells that were detached by application
      of fluid shear stress with values that ranged from 2.3 to 185 dyne/cm2. The
      median shear stress of detachment of KG1a cells was directly related to the
      duration of membrane contact and the amount of immobilized monoclonal antibody
      (anti-CD34). CONCLUSIONS: The hollow-fiber assay provides a general method to
      determine functional properties of molecular domains that interact with cell
      surface receptors and markers.

PMID- 14699605
TI  - Discrimination of the Hoechst side population in mouse bone marrow with violet
      and near-ultraviolet laser diodes.
AB  - BACKGROUND: Discrimination of stem cells with flow cytometric analysis of Hoechst
      33342 efflux by the ABCG2 transporter (termed the Hoechst side population, or SP
      technique) is a valuable methodology for identifying bone marrow progenitors
      enriched with stem cells. Unfortunately, it requires a ultraviolet (UV) laser
      source, usually necessitating an expensive and maintenance-intensive argon- or
      krypton-ion gas laser on a large-scale cell sorter. In this study, we evaluated
      the ability of recently available violet and near-UV laser diodes to discriminate
      Hoechst SP on smaller cuvette-based flow cytometers. METHODS: Violet laser diodes
      (emitting at 408 and 401 nm) and a near-UV laser diode (emitting at 370 nm) were
      mounted on a BD Biosciences LSR II and evaluated for their ability to
      discriminate Hoechst SP in murine bone marrow. RESULTS: The violet laser diodes
      discriminated the Hoechst SP, but with poorer resolution than with the standard
      UV gas laser on a large-scale cell sorter. The near-UV laser diode, in contrast,
      gave excellent Hoechst SP resolution. CONCLUSIONS: These evaluations indicated
      that near-UV laser diodes give excellent Hoechst SP resolution on cuvette-based
      instruments. As the next generation of cell sorters integrate cuvette-based cell
      interrogation into conventional jet-in-air cell separation, these laser sources
      should become applicable for analysis and physical separation of Hoechst SP
      cells.

PMID- 14699606
TI  - Cytokine upregulation of surface antigens correlates to the priming of the
      neutrophil oxidative burst response.
AB  - BACKGROUND: Neutrophil activation is strongly related to organ dysfunction that
      occurs during systemic inflammatory responses. The aim of our study was to
      analyze the oxidative burst response in correlation to the up- and downregulation
      of N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) receptors and the surface
      antigens CD11b, CD62L, and CD66b as potential surrogate markers of the degree of
      neutrophil priming for an increased oxidative burst response induced by
      proinflammatory cytokines. METHODS: Blood was taken from healthy donors.
      Neutrophils were pretreated with cytokines (interleukin [IL]-1beta, IL-6, IL-8,
      granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis
      factor alpha [TNFalpha]; 0.01-10 ng/ml) and stimulated with fMLP (100 nM) in
      vitro. Functional and phenotypical parameters were quantified flow
      cytometrically. RESULTS: The oxidative burst response increased after priming
      with 0.1 ng/ml TNFalpha, 1 ng/ml GM-CSF, or 10 ng/ml IL-8. Upregulation of fMLP
      receptors, CD11b, and CD66b and downregulation of CD62L showed a close
      correlation to the oxidative burst response. Altered expression of these
      parameters partly reached significance at lower cytokine concentrations in
      comparison with the oxidative burst. IL-1beta and IL-6 had no effect.
      CONCLUSIONS: Our results showed that the expression of phenotypical parameters
      closely correlates with functional parameters in human neutrophils. Thus an up-
      or downregulation of antigens such as CD11b or CD62L reflects cytokine-induced
      functional changes.

PMID- 14699607
TI  - Cosegregation of C-insertion at position 961 with the A1555G mutation of the
      mitochondrial 12S rRNA gene in a large Chinese family with maternally inherited
      hearing loss.
AB  - Mutations in the mitochondrial DNA have been shown to be one of the most
      important causes of sensorineural hearing loss. Here, we report the
      characterization of a large Chinese family (507 members in six generations) with
      maternally inherited non-syndromic hearing loss. Members of this family showed
      variable severity and age-of-onset of hearing impairment. In particular, the
      average age at onset of hearing loss in this family changed from 49 years
      (generation III) to 3 years (generation VI). Sequence analysis of the complete
      mitochondrial genome in this pedigree revealed the presence of a homoplasmic
      A1555G mutation in the 12S rRNA gene and other nucleotide changes. Of these
      changes, a C insertion at position 961 in the 12S rRNA gene is of special
      interest as mutations at this position have been found to be associated with
      aminoglycoside induced deafness in several genetically unrelated families. These
      data imply that the C insertion at position 961 in the 12S rRNA gene, acting as a
      secondary factor, could play a role in the phenotypic expression of the deafness
      associated A1555G mutation.

PMID- 14699608
TI  - Segregation of a t(1;3) translocation in multiple affected family members with
      both types of adjacent-1 segregants.
AB  - A subtle balanced translocation involving the terminal regions of 1q and 3p was
      identified in a large family by high-resolution karyotype analysis and confirmed
      by fluorescence in situ hybridization (FISH) analysis. In this family,
      segregation of a balanced t(1:3)(q42.3;p25) chromosome translocation led to two
      types of viable unbalanced complements. The proband inherited the derivative
      chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A
      paternal uncle and cousin had the reciprocal rearrangement with a derivative of
      chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p.
      While profound mental and physical retardation and congenital heart defects were
      characteristics for both rearrangements, facial dysmorphism was quite distinct
      for each imbalance. Individuals who had the derivative chromosome 3 had a long
      face, wide eyebrows, small palpebral fissures, hypertelorism, prominent glabella,
      a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In
      contrast, family members with the derivative of chromosome 1 had a tall forehead
      with bifrontal narrowing, full and large cheeks, and large simple ears. Since the
      translocated segments are small and approximately equal in size in this family,
      it is not surprising that viability was seen in individuals with both types of
      adjacent-1 segregation. In this kindred, the ratio of normal to abnormal
      individuals born to balanced carriers is believed to be about 1:1.5. This
      suggests that the recurrence risk for carriers is 50%.

PMID- 14699609
TI  - Immunohistochemical FMRP studies in a full mutated female fetus.
AB  - Fragile X syndrome (FXS) is the most common form of inherited mental retardation.
      Clinical manifestations are due to the absence of the FMRP protein. Affected
      patients have widely variable phenotypes which are more variable in females than
      males, presumable due to X inactivation. We report the expression pattern of FMRP
      in cerebral cortex and ovary in a control and a full-mutated female fetus. FMRP
      was expressed in mutated and control fetal tissues, although at different levels
      and patterns. Control fetal cerebral cortex showed FMRP expression in almost all
      cells, whereas the full mutation carrier showed FMRP positivity in roughly 50% of
      cortical cells without any specific pattern. In the ovary samples, FMRP
      expression was seen in all germ cells surrounded by FMRP-negative paragranulosa
      and interstitial cells. The Mullerian epithelium of the fetal Fallopian tube was
      continuously positive in the control case, whereas the full mutation carrier
      showed a discontinuous patchy pattern. Expression of homologue proteins FXR1P and
      FXR2P showed no differences between control and full mutation fetuses. The
      pattern of FMRP expression in full mutation carrier females is in agreement with
      a random X-inactivation in maturing fetal tissues. Immunohistochemical results on
      cerebral tissues provide a clue for the variation of mental affection among
      female carriers, depending not only on the number of cells devoid of FMRP, but
      also on the ultimate destination of those cells in sensitive or more silent
      location for a proper cerebral development.

PMID- 14699610
TI  - Results of a genome-wide linkage scan for stuttering.
AB  - We performed a linkage study of stuttering using 392 markers distributed across
      the genome in a series of 68 families identified in the general outbred
      population of North America and Europe. Standardized diagnosis was performed
      using recorded samples of both conversation and reading, in which stuttering
      dysfluencies were scored as percentage of dysfluent words and syllables. Analysis
      was first performed using non-parametric methods implemented in GENEHUNTER, where
      we obtained maximum statistical support for markers of chromosome 18, with a
      maximum NPL (Sall) of 1.51 at D18S976. The single largest pedigree within our
      sample (pedigree 0006) alone gave an NPL of 4.72 at D18S976. For fine mapping, we
      analyzed 18 markers on chromosome 18 across all families using ALLEGRO. Overall
      NPL (Srobdom) scores >5 were obtained with markers on 18p, and Z(lr) scores
      >/=2.5 on 18p and proximal 18q. Furthermore, pedigree 0006 alone gave an NPL
      (Srobdom) of 5.35. Overall our results suggest chromosome 18 may harbor a
      predisposing locus for this disorder, and additional genes may exist.

PMID- 14699611
TI  - The 10q24-linked split hand/split foot syndrome (SHFM3): narrowing of the
      critical region and confirmation of the clinical phenotype.
AB  - In this communication we describe the clinical and molecular genetic findings in
      a family with a variable ectrodactyly linked to SHFM3. This is only the second
      detailed report of the clinical features of the SHFM3 linked syndrome in a large
      pedigree. Within this family the expressivity of the condition ranges from the
      classical ectrodactyly deformity to partial absence of the thumb and agenesis of
      the distal tip of the index finger. There is discordant limb severity, with the
      feet more severely affected than the hands. Two individuals have a nail dysplasia
      indicating the presence of a minor ectodermal component. A cleft palate was
      present in one individual. Radiological features of family members include short
      metacarpals with rounded proximal heads, agenesis of the radial ray, epiphysial
      coning, and an unusual supernumerary ossicle opposed to the distal phalanx of the
      left thumb. Genetic mapping studies in this family exclude p63 involvement and
      demonstrate that ectrodactyly in this pedigree is linked to the SHFM3 region on
      chromosome 10q24. A meiotic recombination event enabled exclusion of a maximum of
      1.9 Mb of DNA from the previously known critical region thereby narrowing the
      critical interval to between D10S1265 and D10S222, with the minimal critical
      region being between D10S1240 and D10S1267. Further investigations are in
      progress to identify the gene within the SHFM3 critical region responsible for
      ectrodactyly.

PMID- 14699612
TI  - Canavan disease: carrier-frequency determination in the Ashkenazi Jewish
      population and development of a novel molecular diagnostic assay.
AB  - Canavan disease (CD) is an autosomal recessive progressive neurodegenerative
      disorder prevalent in the Ashkenazi Jewish (AJ) population. The carrier rate for
      the most common mutations that cause CD in the AJ population is often quoted as
      1:37-1:40. This is not supported by our finding of only two diagnosed cases of CD
      in the last 20 years in the Toronto AJ population of 160,000 and an estimated
      birth rate of 1,500-2,000 per year. Therefore, we embarked on a prevalence cross
      sectional screening study to determine the carrier rate of CD in this population.
      In order to perform low-cost, high-throughput population testing for CD using
      molecular techniques, we first developed a novel molecular assay using multiplex
      fluorescent allele specific polymerase chain reaction (PCR) to test for the three
      most common mutations causing CD in the AJ population (A854C, C693A, C914A) and a
      neutral polymorphism at the site of the C693A mutation. During testing it was
      noted that individuals who were carriers of the A854C mutation also had a T
      polymorphism at the site of the C693A mutation (Y231X). We confirmed that in all
      A854C carriers the 854C mutation was in disequilibrium with the 693T
      polymorphism, indicating a founder chromosome for the A854C mutation in the AJ
      population. Twenty-five carriers were found from 1,423 samples yielding a carrier
      rate of 1:57, differing from the widely quoted frequency of 1:40 and supporting
      our observed frequency of disease.

PMID- 14699613
TI  - Longterm follow-up in chondrodysplasia punctata, tibia-metacarpal type,
      demonstrating natural history.
AB  - We report the longterm clinical and radiological progression in three unrelated
      patients with the tibia-metacarpal form of chondrodysplasia punctata (CDP-TM).
      The patients were followed for 37, 25, and 32 years, respectively. At follow-up
      intellectual function was normal, and physical function was well preserved. There
      was also marked resolution of several significant early radiographic features.
      The patients attained adult heights of 152, 138, and 148 cm. Two patients had
      chronic serous otitis media requiring tympanostomy tubes during childhood. One
      patient suffered persisting back pain related to spinal stenosis and required
      lumbar laminectomy at the age of 26 years. One patient had hip dysplasia
      requiring orthopedic surgical intervention. All patients had recurrent patella
      dislocation. Sterol and very long chain fatty acid profiles, FISH analysis for
      SHOX gene deletions, blood lymphocyte karyotype, and phytanic acid levels were
      normal in those tested, and no mutations in arylsulfatase D and E genes were
      detected. These data suggest that the longterm clinical and functional prognosis
      in this condition appears to be better than that expected based on initial
      clinical and radiological findings.

PMID- 14699614
TI  - Unexpected death and critical illness in Prader-Willi syndrome: report of ten
      individuals.
AB  - Individuals with Prader-Willi syndrome (PWS) generally survive into adulthood.
      Common causes of death are obesity related cor pulmonale and respiratory failure.
      We report on a case series of eight children and two adults with unexpected death
      or critical illness. Our data show age-specific characteristics of PWS patients
      with fatal or life-threatening illnesses. Under the age of 2 years, childhood
      illnesses in general were associated with high fever and rapid demise or near
      demise. Hypothalamic dysfunction likely plays a role in exaggerated fever
      response, but also perhaps in central regulation of adrenal function. Below
      average sized adrenal glands were found in three children, which raises the
      possibility of unrecognized adrenal insufficiency in a subset of individuals with
      PWS and emphasizes the vital role of autopsy. The tub drowning death of an adult
      patient could be related to central hypersomnia, which has been reported in PWS.
      We suggest that increased risk for critical illness be considered in the
      discussion of anticipatory guidance for the care of infants with PWS. Since a
      number of children died while hospitalized, particularly close observation of PWS
      children who are ill enough to warrant hospital admission is recommended.

PMID- 14699615
TI  - Search for somatic 22q11.2 deletions in patients with conotruncal heart defects.
AB  - A wide range of clinical variability in patients with 22q11.2 deletions has been
      demonstrated in numerous studies. Nevertheless, it is still an open question if
      major genetic factors contribute to clinical expression. Therefore one aim of
      this study was to investigate, if patients with 22q11.2 deletion and conotruncal
      heart defects show a "second hit" somatic 22q11.2 deletion in tissue from the
      conotruncus, heart vessels or thymus. The second aim was to analyse patients with
      conotruncal heart defects without 22q11.2 deletion in blood cells for somatic
      deletion mosaicism. We were able to study tissue samples from heart surgery from
      23 patients, 9 of whom had 22q11 deletions by FISH analysis on metaphase spreads
      from peripheral lymphocytes. Analysis of 18 polymorphic markers from the 22q11.2
      region in DNA prepared from thymus and/or heart vessels and/or conotruncus tissue
      and peripheral lymphocytes in each patient did not show any allelic loss. Thus
      somatic 22q11.2 deletions apparently do not play a major role in conotruncal
      heart defects in patients with or without germ line 22q11.2 deletion.

PMID- 14699616
TI  - Partial duplication 2p as the sole abnormality in two cases with anencephaly.
AB  - Anencephaly/NTD has been observed in aneuploid and non-aneuploid individuals. We
      present two cases of anencephaly diagnosed prenatally with partial duplication of
      the short arm of chromosome 2 as the sole abnormality. The absence of aneuploidy
      involving other regions of the genome in these cases, further substantiates
      suggestions of the existence of a gene or genes on the short arm of chromosome 2
      critical in the development of the central nervous system.

PMID- 14699617
TI  - A girl with duplication 17p10-p12 associated with a dicentric chromosome.
AB  - We report a 7 1/2-year-old girl with an approximately 9.5 Mb duplication of
      proximal 17p. Her clinical features include moderately severe developmental
      delay, absence of speech, talipes, congenital dislocation of the hips, premature
      adrenarche, dysmorphic facial features, deep palmar creases, and signs and
      symptoms of peripheral neuropathy consistent with Charcot-Marie-Tooth disease
      type 1A (CMT1A). Chromosome analysis revealed a partially duplicated 17p with two
      centromeres on the derivative chromosome. Fluorescence in situ hybridization
      (FISH) analysis demonstrated the tandemly duplicated segment spans 17p10-p12,
      including the entire Smith-Magenis syndrome (SMS) critical region and a portion
      of the CMT1A critical region. One breakpoint mapped within the centromere and the
      second breakpoint mapped within the CMT1A critical region, distal to the PMP22
      gene. Microsatellite polymorphism studies showed that the duplicated chromosome
      is of maternal origin. We compare the clinical features of our patient to those
      of individuals with partial trisomy of proximal 17p to further delineate the
      genotype-phenotype correlation associated with segmental duplication of this
      chromosomal region.

PMID- 14699618
TI  - Interstitial deletion 9q22.32-q33.2 associated with additional familial
      translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and
      features of Nail-Patella syndrome.
AB  - The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS,
      #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a
      few cases of interstitial deletion of chromosome 9q. We present an 11-year-old
      girl with clinical features consistent with BCNS including bridging of sella
      turcica, biparietal bossing, downward slanting palpebral fissures, mandible
      prognathism, pectus excavatum, thumb abnormalities, occult spina bifida at L5-S4,
      numerous basal cell nevi, and single basal cell carcinoma. Cytogenetic analysis
      using high-resolution banding techniques and fluorescence in situ hybridization
      (FISH) revealed interstitial chromosome deletion 9q22.32-q33.2 involving the PTCH
      gene as a secondary breakage event to a chromosome translocation
      t(9;17)(q34.1;p11.2)mat. Further FISH studies showed the translocation breakpoint
      on 9q34.11 maps proximal to ABL, between the BAC clone RP11-88G17 and the LMX1B
      gene. The latter gene encodes a transcription factor, in which loss of function
      mutations are responsible for the nail-patella syndrome (NPS, #161200 OMIM).
      Interestingly, some features of our proband (e.g., bilateral patellar dysplasia
      and abnormal clavicular shape), as well as her healthy sister who carries the
      same translocation, are also found in patients with NPS. The chromosome 17p11.2
      breakpoint maps in the Smith-Magenis syndrome common deletion region, within two
      overlapping BAC clones, CTD-2354J3 and RP11-311F12.

PMID- 14699619
TI  - Facial hemangioma and malformation of the cortical development: a broadening of
      the PHACE spectrum or a new entity?
AB  - Facial hemangioma is usually isolated but its association with craniocervical
      arterial anomalies and structural brain malformations is well known. The acronym
      PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial
      anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to
      indicate that disorder in which brain anomalies are mainly represented by the
      Dandy-Walker malformation. We report on a 10-month-old boy affected by facial
      hemangioma and a complex cortical dysplasia located in the left frontal region.
      The lesion was characterized by a deeply infolding pachygyric cortex and a band
      of gray matter lining the wall of the lateral ventricle. The entire left cerebral
      hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures
      or cardiac/aortic malformations were present. An overlapping
      clinical/pathological pattern was previously reported in another patient with
      facial hemangioma and cerebrovascular anomalies. These observations seem to
      indicate that the facial hemangiomas may be associated with disorders of the
      cortical development.

PMID- 14699620
TI  - A case of Costello with parathyroid adenoma and hyperprolactinemia.
AB  - A 23-year-old female with Costello syndrome is presented. She had mental
      retardation, macrocephalia, "coarse" facial features, deep palmar and plantar
      creases, hyperkeratosis in palms and soles, hyperpigmentation, curly hair, and
      cutis laxa, which are among the diagnostic features of the syndrome, and a
      history of hyperprolactinemia since the age of 16. Her present complaint was
      weakness and widespread bone-pain. In routine biochemistry, she had an elevated
      calcium level of 11.1 (8.6-10.2) mg/dl and her DEXA evaluation was consistent
      with osteoporosis (vertebra and femur T score <-2.5). High PTH levels, 103 (8-78)
      pg/ml, suggested presence of a parathyroid adenoma. Tc-MIBI scintigraphy revealed
      two focuses of pathological uptake, one located inferior to left lobe of thyroid
      and the other in the superior left lobe of thyroid gland. After parathyroid
      adenomectomy, her serum calcium and PTH levels returned to normal values. This is
      the first case of parathyroid adenoma and hyperprolactinemia in the literature,
      reported in a patient with Costello syndrome.

PMID- 14699621
TI  - A newly recognized syndrome with double upper and lower lip, hypertelorism,
      eyelid ptosis, blepharophimosis, and third finger clinodactyly.
AB  - Congenital double lip is an uncommon developmental abnormality usually affecting
      the upper lip. We report a 21-year-old male with double upper and lower lip,
      hypertelorism, unilateral ptosis, blepharophimosis, and broad nose with broad
      nasal tip, highly arched palate, and bilateral third finger clinodactyly. The
      disorder differs from Ascher syndrome and appears to represent a newly recognized
      syndrome.

PMID- 14699622
TI  - New syndrome: focal dermal hypoplasia, morning glory anomaly, and polymicrogyria.
AB  - Regional skin hypoplasia has been described in several genetic syndromes,
      including focal dermal hypoplasia (FDH), microphthalmia with linear skin defects
      (MLS), oculocerebrocutaneous syndrome (OCCS), and terminal osseous dysplasia and
      pigmentary defects (TODP). All but OCCS have been reported to follow an X-linked
      inheritance pattern. We describe a 14-year-old girl with clinical features
      overlapping with these disorders. She had mild mental retardation, macrocephaly,
      microphthalmia, right-sided morning glory optic disc anomaly, palmar and lip
      pits, and polysyndactyly. A swirling pattern of skin hypopigmentation, papular
      hypopigmented and herniated skin lesions reminiscent of FDH most prominent over
      her face, head, hands, and feet was evident. Brain magnetic resonance imaging
      (MRI) showed polymicrogyria (most severely in the perisylvian and mesial frontal
      regions), enlarged left lateral ventricle, partial agenesis of the corpus
      callosum, and optic nerve tumor on the right. Dermatopathologic examination of
      the skin lesions was consistent with basaloid follicular hamartomas. The skin and
      digit anomalies observed overlap with FDH, but polymicrogyria, basaloid
      follicular hamartomas, optic nerve tumor, and morning glory anomaly have not
      previously been described in FDH. Skin defects in MLS are linear and the eyes
      typically have sclerocornea. Polymicrogyria has been described in OCCS, but not
      in any of the other three syndromes. The limb anomalies in TODP are reductions
      rather than polysyndactyly. Skin defects are localized to the face, and digital
      fibromas usually occur. While significant overlap exists between all four of the
      syndromes discussed, we believe that the constellation of anomalies observed in
      this girl most likely comprises a newly recognized syndrome.

PMID- 14699623
TI  - Hepatic fibrosis in Kabuki syndrome.
AB  - Kabuki (Niikawa-Kuroki) syndrome (KS) is characterized by a distinctive face,
      mental retardation, growth deficiency, skeletal anomalies, dermatoglyphic
      abnormalities, palatal anomalies, congenital heart defects, and urogenital
      malformations. Congenital hepatic abnormalities have been sporadically described
      in patients with KS from the literature, consisting of extrahepatic biliary
      atresia, neonatal sclerosing cholangitis, and severe neonatal jaundice. We report
      here on an additional patient with a congenital abnormality of the liver
      consisting of hepatic fibrosis. To our knowledge, idiopathic congenital hepatic
      fibrosis has not been reported in KS. Thus, our observation expands the spectrum
      of liver malformations found in KS with the inclusion of hepatic fibrosis and
      supports the evidence that hepatic abnormalities may not be uncommon in KS.
      Clinician should be advised to search for the specific facial anomalies of KS in
      patients with syndromic congenital hepatic diseases, and KS should be added to
      the list of previously recognized multiple congenital anomaly syndromes with
      hepatic involvement. Due to the frequent association with congenital heart
      malformations, KS should be considered in the evaluation of patients with
      neonatal liver disease and cardiac malformation. Due to the expression patterns
      of Notch genes, involvement of the Notch signaling pathway in the development of
      heart and liver anomalies in KS should be considered.

PMID- 14699624
TI  - Fragile X and mosaic 45,X/46,XY mixed gonadal dysgenesis in a girl with ambiguous
      genitalia.

PMID- 14699625
TI  - Response to Moirand et al.-"HFE based re-evaluation of heterozygous
      hemochromatosis".

PMID- 14699626
TI  - Re: Article by Kamath et al.-"Facial features in Alagille Syndrome".

PMID- 14699630
TI  - Hemangioblasts, angioblasts, and adult endothelial cell progenitors.
AB  - After decades of speculation, proof of embryonic hemangioblasts finally emerged a
      few years ago. Surprisingly, at about the same time, evidence for adult
      hemangioblasts began to appear, and recent single-cell bone marrow transplants
      have confirmed their existence. Embryonic and adult hemangioblasts appear to
      share antigenic determinants, including CD34, ACC133, and VEGFR2, although their
      phenotype may be plastic. They also respond to similar factors, prominent among
      them vascular endothelial growth factor (VEGF). In the adult, hemangioblasts
      reside principally in the bone marrow, although they may subsequently leave that
      niche to reside in nonhematopoietic tissues. A number of studies indicate that
      these cells or their progeny may be a significant source of endothelial cells in
      adult pathologic and nonpathologic vascularization, and may participate in
      vascular repair. In addition to hemangioblasts, a more differentiated source of
      endothelial cell progenitors may be present in the blood, namely, monocytes or
      monocytic-like cells. The relative importance of the two cell types in vivo is
      not clear, though endothelial cells derived from the two sources may not be
      identical, and hemangioblasts seem to provide a stimulus for differentiation of
      the monocytes. Treatment with exogenous bone marrow-derived cells can promote
      neovascularization, accelerate restoration of blood flow to ischemic tissues, and
      improve cardiac function after infarct. Hence, there is great hope that either
      alone, in combination with angiogenic factors, or as gene therapy vectors, we can
      harness these cells to treat ischemic and vascular diseases in the relatively
      near future.

PMID- 14699629
TI  - Stem cells and the formation of the myocardium in the vertebrate embryo.
AB  - A major goal in cardiovascular biology is to repair diseased or damaged hearts
      with newly generated myocardial tissue. Stem cells offer a potential source of
      replacement myocytes for restoring cardiac function. Yet little is known about
      the nature of the cells that are able to generate myocardium and the conditions
      they require to form heart tissue. A source of information that may be pertinent
      to addressing these issues is the study of how the myocardium arises from
      progenitor cells in the early vertebrate embryo. Accordingly, this review will
      examine the initial events of cardiac developmental biology for insights into the
      identity and characteristics of the stem cells that can be used to generate
      myocardial tissue for therapeutic purposes.

PMID- 14699631
TI  - Smooth muscle stem cells.
AB  - Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor
      cells. In the embryo, the most well studied SMC progenitor is the cardiac neural
      crest stem cell. Smooth muscle differentiation in the neural crest lineage is
      controlled by a combination of cell intrinsic factors, including Pax3, Tbx1,
      FoxC1, and serum response factor, interacting with various extrinsic factors in
      the local environment such as bone morphogenetic proteins (BMPs), Wnts,
      endothelin (ET)-1, and FGF8. Additional sources of multipotential cells that give
      rise to vascular SMCs in the embryo include proepicardial cells and possibly
      endothelial progenitor cells. In the adult, vascular SMCs must continually repair
      arterial injuries and maintain functional mass in response to changing demands
      upon the vessel wall. Recent evidence suggests that this is accomplished, in
      part, by recruiting multipotential vascular progenitors from bone marrow-derived
      stem cells as well as from less well defined sources within adult tissues
      themselves. This article will review our current understanding of the origins of
      vascular SMCs from multipotential stem and progenitor cells in developing as well
      as adult vasculature.

PMID- 14699632
TI  - Cardiac neural crest stem cells.
AB  - Whereas the heart itself is of mesodermal origin, components of the cardiac
      outflow tract are formed by the neural crest, an ectodermal derivative that gives
      rise to the peripheral nervous system, endocrine cells, melanocytes of the skin
      and internal organs, and connective tissue, bone, and cartilage of the face and
      ventral neck, among other tissues. Cardiac neural crest cells participate in the
      septation of the cardiac outflow tract into aorta and pulmonary artery. The
      migratory cardiac neural crest consists of stem cells, fate-restricted cells, and
      cells that are committed to the smooth muscle cell lineage. During their
      migration within the posterior branchial arches, the developmental potentials of
      pluripotent neural crest cells become restricted. Conversely, neural crest stem
      cells persist at many locations, including in the cardiac outflow tract. Many
      aspects of neural crest cell differentiation are driven by growth factor action.
      Neurotrophin-3 (NT-3) and its preferred receptor, TrkC, play important roles not
      only in nervous system development and function, but also in cardiac development
      as deletion of these genes causes outflow tract malformations. In vitro clonal
      analysis has shown a premature commitment of cardiac neural crest stem cells in
      TrkC null mice and a perturbed morphology of the endothelial tube. Norepinephrine
      transporter (NET) function promotes the differentiation of neural crest stem
      cells into noradrenergic neurons. Surprisingly, many diverse nonneuronal
      embryonic tissues, in particular in the cardiovascular system, express NET also.
      It will be of interest to determine whether norepinephrine transport plays a role
      also in cardiovascular development.

PMID- 14699633
TI  - The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells.
AB  - After its initial formation the epicardium forms the outermost cell layer of the
      heart. As a result of an epithelial-to-mesenchymal transformation (EMT)
      individual cells delaminate from this primitive epicardial epithelium and migrate
      into the subepicardial space (Perez-Pomares et al., Dev Dyn 1997; 210:96-105;
      Histochem J 1998a;30:627-634). Several studies have demonstrated that these
      epicardially derived cells (EPDCs) subsequently invade myocardial and
      valvuloseptal tissues (Mikawa and Fischman, Proc Natl Acad Sci USA 1992;89:9504
      9508; Mikawa and Gourdie, Dev Biol 1996;174:221-232; Dettman et al., Dev Biol
      1998;193:169-181; Gittenberger de Groot et al., Circ Res 1998;82:1043-1052;
      Manner, Anat Rec 1999;255:212-226; Perez-Pomares et al., Dev. Biol. 2002b;247:307
      326). A subset of EPDCs continue to differentiate in a variety of different cell
      types (including coronary endothelium, coronary smooth muscle cells (CoSMCs),
      interstitial fibroblasts, and atrioventricular cushion mesenchymal cells),
      whereas other EPDCs remain in a more or less undifferentiated state. Based on its
      specific characteristics, we consider the EPDC as the ultimate 'cardiac stem
      cell'. In this review we briefly summarize what is known about events that relate
      to EPDC development and differentiation while at the same time identifying some
      of the directions where EPDC-related research might lead us in the near future.

PMID- 14699634
TI  - Cardiovascular potential of embryonic stem cells.
AB  - Initial events involved in the process of heart formation consist of myocardial
      differentiation as well as development of endothelial and endocardial tissues. As
      only limited means are allocated to the studying of cardiovascular system
      development, embryonic stem cells (ESCs) isolated from the inner cell mass (ICM)
      of developing mice or human blastocysts offer the first step toward the
      understanding of these complex and intriguing events. ESCs are able to
      differentiate into a wide range of cell types, including various vascular cells
      and cardiomyocytes, and their self-renewal capability renders them a unique,
      homogeneous, and unlimited preliminary population of cells for the investigation
      of early developmental events of cardiovascular system and lineage commitment.
      This review summarizes the accumulated knowledge of the cellular and molecular
      mechanisms involved in the development of the cardiovascular system.

PMID- 14699635
TI  - Blood cell progenitors: insights into the properties of stem cells.
AB  - Hematopoiesis is a dynamic process in which eight lineages of mature blood cells
      are derived from a common stem cell. Great progress has been made in identifying
      the functionally disparate progenitors that emerge from the stem cell and in
      elucidating the molecules required for their growth and survival. Further work
      will be required to understand the molecular mechanisms that regulate commitment
      of stem and progenitor cells to each stage of progenitor cell development and
      ultimately into the mature blood cells.

PMID- 14699636
TI  - Adult stem cells.
AB  - Development of a multicellular organism is accomplished through a series of
      events that are preprogrammed in the genome. These events encompass cellular
      proliferation, lineage commitment, lineage progression, lineage expression,
      cellular inhibition, and regulated apoptosis. The sequential progression of cells
      through these events results in the formation of the differentiated cells,
      tissues, and organs that constitute an individual. Although most cells progress
      through this sequence during development, a few cells leave the developmental
      continuum to become reserve precursor cells. The reserve precursor cells are
      involved in the continual maintenance and repair of the tissues and organs
      throughout the life span of the individual. Until recently it was generally
      assumed that the precursor cells in postnatal individuals were limited to lineage
      committed progenitor cells specific for various tissues. However, studies by
      Young, his colleagues, and others have demonstrated the presence of two
      categories of precursor cells that reside within the organs and tissues of
      postnatal animals. These two categories of precursor cells are lineage-committed
      (multipotent, tripotent, bipotent, and unipotent) progenitor cells and lineage
      uncommitted pluripotent (epiblastic-like, ectodermal, mesodermal, and endodermal)
      stem cells. These reserve precursor cells provide for the continual maintenance
      and repair of the organism after birth.

PMID- 14699637
TI  - Adult stem cells and their cardiac potential.
AB  - Adult cardiac muscle is unable to repair itself following severe disease or
      injury. Because of this fundamental property of the myocardium, it was long
      believed that the adult myocardium is a postmitotic tissue. Yet, recent studies
      have indicated that new cardiac myocytes are generated throughout the life span
      of an adult and that extracardiac cells can contribute to the renewal of
      individual cells within the myocardium. In addition, investigations of the
      phenotypic capacity of adult stem cells have suggested that their potential is
      not solely restricted to the differentiated cell phenotypes of the source tissue.
      These observations have great implications for cardiac biology, as stem cells
      obtained from the bone marrow and other readily accessible adult tissues may
      serve as a source of replacement cardiac myocytes. In this review, we describe
      the evidence for these new findings and discuss their implications in context of
      the continuing controversy over stem cell plasticity.

PMID- 14699638
TI  - ADAP squeaks by...again.

PMID- 14699639
TI  - The AIDS Survival Project story: 15 years of advocacy, self-empowerment,
      partnership.

PMID- 14699640
TI  - 8 simple rules for managing those holiday blues.

PMID- 14699641
TI  - Is bio2010 the right blueprint for the biology of the future?

PMID- 14699642
TI  - Scientific Psychiatry?

PMID- 14699643
TI  - Revisiting Amazonia circa 1492.

PMID- 14699644
TI  - Chronic renal failure after transplantation of a nonrenal organ.

PMID- 14699645
TI  - Chronic renal failure after transplantation of a nonrenal organ.

PMID- 14699646
TI  - Chronic renal failure after transplantation of a nonrenal organ.

PMID- 14699647
TI  - Withdrawal of mechanical ventilation.

PMID- 14699648
TI  - Withdrawal of mechanical ventilation.

PMID- 14699649
TI  - Withdrawal of mechanical ventilation.

PMID- 14699650
TI  - Warfarin prophylaxis in the antiphospholipid antibody syndrome.

PMID- 14699651
TI  - Warfarin prophylaxis in the antiphospholipid antibody syndrome.

PMID- 14699652
TI  - Warfarin prophylaxis in the antiphospholipid antibody syndrome.

PMID- 14699654
TI  - Self-reported therapeutic errors to a poison control center.
AB  - BACKGROUND: The techniques for avoiding medication errors in healthcare settings
      can be extrapolated to improving pharmaceutical care and medication safety in the
      patient's home. Understanding patient self-dosing errors in self dosing is
      important in the development of prevention strategies. OBJECTIVE: To examine
      cases of therapeutic errors in patient self dosing as reported to the Oklahoma
      Poison Control Center, with the goal of proposing prevention strategies and
      education. METHODS: A retrospective study of self-dosing errors was performed
      examining root cause, patient age, and pharmaceutical agent. RESULTS: Patient
      self-dosing errors accounted for 8.75% of all poison control exposures as
      compiled by the Oklahoma Poison Control Center in 2001. The most common reasons
      for therapeutic errors in all age groups involved taking or giving the wrong
      formulation or concentration, inadvertently taking/giving medication twice and
      another incorrect dose. CONCLUSION: Patient education is the key to preventing
      therapeutic errors in the home.

PMID- 14699653
TI  - Primary aortoenteric fistula to jejunum: a case report.
AB  - Primary aortoenteric fistula (PAEF) is a well-known but rare cause of
      gastrointestinal bleeding. The diagnosis can be difficult since the majority of
      patients do not have classical symptoms. "Herald bleed" is usually followed by a
      massive hemorrhage. Endoscopy and radiographic studies can assist in diagnosis.
      We present the case of 56-year-old male with PAEF who presented with obscure
      gastrointestinal bleeding. Endoscopic studies were unremarkable. Computed
      tomography (CT) in this stable but symptomatic patient helped in establishing
      diagnosis of PAEF. Patient underwent laparotomy with aortobifemoral graft
      placement. A high index of suspicion, early diagnosis and prompt appropriate
      surgical intervention are crucial for survival of these patients.

PMID- 14699655
TI  - Psychological issues associated with terrorism: a guide for physicians.

PMID- 14699656
TI  - Oklahoma Medical Board history: Part I.

PMID- 14699657
TI  - You're the boss: understanding your responsibilities as an employer.

PMID- 14699659
TI  - Patient page #43. Smoking cessation.

PMID- 14699658
TI  - Smoke-Free Beginnings.
AB  - Because of the high prevalence of smoking in pregnant women in Oklahoma, the
      Oklahoma State Medical Association has received a grant funded by the Robert Wood
      Johnson Foundation to conduct a project aimed at system-level changes that
      promote smoking cessation. The Smoke-Free Beginnings project is emphasizing
      practical strategies that can be easily integrated into routine practice. Join
      colleagues statewide in thirty two different practices offering prenatal care in
      assisting pregnant women to live free of tobacco addiction. To participate, or
      for more information, please contact Sarah Jane Carlson at the Oklahoma State
      Medical Association at 405.843.9521 or 800.522.9452 or email at
      Carlson@osmaonline.org. Our newborns and mothers will benefit greatly from this
      project, and the state of Oklahoma will be a leader in the development of a
      system-wide intervention to aid in the dissemination of the Best Practice
      Guidelines.

PMID- 14699661
TI  - [Professor Teresa Wyszynska: great nephrologist--my master].

PMID- 14699662
TI  - [Monogenic hereditary congenital nephrotic syndrome].

PMID- 14699663
TI  - [Professor Franciszek Kokot-50 years in the field of research].

PMID- 14699664
TI  - [Studies on the renin-angiotensin-aldosterone system as an example of scientific
      achievements of professor Franciszek Kokot].

PMID- 14699665
TI  - [Scientific career--happy coincidence or ambitious aspiration for exciting
      adventure].

PMID- 14699666
TI  - [Hormonal system in the physiology and pathology of the kidneys].

PMID- 14699667
TI  - [Laboratory tests of endocrine system in chronic renal failure: benefits and
      risks].

PMID- 14699668
TI  - [Reproductive dysfunction in women of reproductive age undergoing hemodialysis].

PMID- 14699669
TI  - [Advances in research on pathogenesis and management of renal osteodystrophy].

PMID- 14699670
TI  - [Prevention of diabetic nephropathy--perspectives].

PMID- 14699671
TI  - [Advances in the diagnosis and treatment of diabetic nephropathy].

PMID- 14699672
TI  - [Erythropoietin in treatment of anemia of non-renal origin].

PMID- 14699673
TI  - [Some issues of acid base disorders in renal diseases].

PMID- 14699674
TI  - [The role of diagnostic tests in renal diseases].

PMID- 14699675
TI  - [Pathogenetic and epidemiological aspects of hypertensive nephropathy].

PMID- 14699676
TI  - [Some aspects of pleiotropic effects of statins in internal medicine].

PMID- 14699677
TI  - [Pleiotropic effect of statins in preventing progression of chronic renal
      disease].

PMID- 14699678
TI  - [Malnutrition in patients with chronic renal failure--how to treat?].

PMID- 14699679
TI  - [Hypertension in predialysis chronic renal insufficiency-- when and how to
      treat?].

PMID- 14699680
TI  - [Anaemia treatment with recombinant human erythropoietin in predialysis patients
      with chronic renal failure--own experience].

PMID- 14699681
TI  - [Monitoring and treatment of dyslipidemia in predialysis patients with chronic
      renal failure].

PMID- 14699682
TI  - [Prophylaxis of renal osteodystrophy].

PMID- 14699683
TI  - [Pre-emptive kidney transplantation].

PMID- 14699684
TI  - [Surgical access for hemodialysis and peritoneal dialysis].

PMID- 14699685
TI  - [Renal replacement therapy in chronic renal failure: when to start?].

PMID- 14699686
TI  - [Skeletal scintigraph and some bone turnover markers in the diagnosis of renal
      osteodystrophy in hemodialysis patients].
AB  - Real osteodystrophy is a spectrum of bone disorders that developing in patients
      (pts) with chronic renal failure. In the recent years several new biochemical
      markers of bone turnover have been proposed for the non-invasive evaluation of
      bone remodeling in hemodialysis (HD) pts The aim of our study was to examine
      serum concentrations (conc.) of some biochemical parameters of bone turnover and
      compare them with the results of bone scintigraphy. We measured serum levels of
      the aminoterminal propeptide of type I procollagen (PINP) as a marker of bone
      formation, and the serum levels of the pyridinoline cross-linked telopeptide
      domain of type I collagen (ICTP) as a marker of bone resorption in a group of 71
      HD pts (35 male, 36 female) with a mean age 56 years. The mean duration of
      treatment was 87 months (range 2-302). We have compared these two collagen
      related peptides with more classical humoral parameters of renal osteodystrophy.
      For that purpose we measured serum concentrations of: intact PTH (iPTH),
      osteocalcin (BGP) and hydroxyproline (Hyd). The control group (CG) consisted of
      22 healthy subjects, mean age 41 years. Whole-body bone scintigraphy was
      performed 2.5 hours after injection of 740 MBq MDP99mTc. The quantification of
      bone images was performed using bone to soft tissue ratio K. The mean conc. of
      PINP were significantly higher in HD pts than in CG (170.0 +/- 125.4 vs 32.3 +/-
      9.3 micrograms/L, p < 0.001). Likewise and mean conc. of ICTP were significantly
      higher in pts than in CG (53.3 +/- 14.2 vs 2.9 +/- 0.7 micrograms/L, p < 0.001).
      We observed that mean conc. of iPTH were significantly higher in pts than in CG
      (575.7 +/- 569.6 vs 32.3 +/- 9.4 pg/ml; p < 0.001). Also the mean conc. of Hyd
      and BCG were higher than in CG (305.3 +/- 95.3 vs 281.5 +/- 53.9 mumoL, p < 0.05
      and respectively 58.6 +/- 27.2 vs 7.4 +/- 2.7 ng/ml, p < 0.001). K ratio was
      significantly higher in patients than in control group (GK) (3.7 +/- 1.2 vs 2.2
      +/- 0.5, p < 0.01). Some significant positive correlations were observed between:
      PINP and ICTP (r = 0.71, p < 0.000001); between: PTH and PINP (r = 0.83, p <
      0.000001) and between: PTH and ICTP (r = 0.49, p < 0.00002). We found significant
      positive correlation between: BGP and PINP (r = 0.83, p < 0.000001) and between:
      BGP and ICTP (r = 0.57, p < 0.0001). No correlation was found between serum Hyd
      levels and other examined biochemical markers of bone turnover in our group of
      pts. Significant correlations were found also between K ratio on one hand and
      PINP (p < 0.01, r = 0.575) and BGP (p < 0.01, r = 0.535) levels on the other. The
      correlation between K ratio and iPTH was slightly significant (p = 0.05, r =
      0.462). We did not find any relationship between other parameters. CONCLUSION: We
      concluded that PINP, ICTP and semiquantative bone scan evaluation are good
      diagnostic tools in the process of bone turnover in hemodialysis patients. The
      long duration of hemodialysis therapy is connected with higher plasma levels of
      ICTP--marker of bone resorption.

PMID- 14699687
TI  - [Risk factors for ischemic heart disease and glycosaminoglycans (GAG's) in plasma
      in atherosclerosis obliterans].
AB  - GAGs (glycosoaminoglycans) derive from damaged artery endothelium cells.
      Theoretically their concentration could be used to measure the level of
      atherosclerosis process. The aim of the study was to estimate the concentration
      of glucosamine and galactosamine in plasma in patients with AO in comparison to
      the main risk factors of CHD: smoking, hyperlipidemia, hypertension. INVESTIGATED
      GROUP: the subject of the study were 35 men and 26 women suffering from AO. The
      control group comprised 20 men and 28 women. People from both groups were 36-65
      years old. The concentration of glucosamine and galactosamine were determined by
      automatic amino acid analyzer LC 6001 Biotronic. The lipids in plasma were
      determined by conventional methods. Results 100% of men and 81% of women with AO
      were smokers to compare 70% and 17% in the control group. Systolic blood pressure
      in men with AO was 134 +/- 13 mm Hg and in women 136 +/- 16 mm Hg. In the control
      groups they were respectively 122 +/- 10 mm Hg and 124 +/- 10 mm Hg. The
      difference between the groups is statistically significant. Diastolic and
      systolic pressures in women with AO were higher then in the control group. In men
      with AO systolic pressure, but not diastolic pressure, was higher than in the
      control group. It was observed that in women with AO the concentration of total
      cholesterol, LDL-chol, apo B in serum, apo B in LDL, TG, TC-HDL-chol/HDL-chol,
      LDL/HDL were higher, HDL-chol was lower in comparison with the control group. In
      men with AO total cholesterol, LDL-chol/HDL-chol and TC-HDL-chol/HDL-chol were
      higher then in the control group, HDL-chol was lower. 80% of women and 74% of men
      with AO suffered from hyperlipidemia compared with 36% and 60% in the control
      group respectively. Mixed hyperlipidemia was the most important factor
      differentiating patients with AO and the control group, when compared to other
      types of hyperlipidemia. The coexistence of risk factors was more frequently
      observed in patient with AO then in the control group. Differences in
      concentrations of glucosamine and galactosamine between the patients with AO and
      the control group were not statistically significant in women and only slightly
      statistically significant in men. CONCLUSIONS: Classical risk factors of CHD
      differentiate patients with AO from the healthy people. The concentrations of
      glucosamine and galactosamine in plasma cannot be used to determine the
      atherosclerosis process.

PMID- 14699688
TI  - [Analysis of serum testosterone, estradiol, dehydroepiandrosterone sulfate and
      gonadotropin concentration and lipid parameters in 50- and 60-year-old men from
      urban population].
AB  - As aging proceeds many different changes occur in endocrine system, particularly
      in the sexual system. In this paper were presented results of studies on 142
      healthy men living in Poznan aged 50 and 60 (group I consisted of 69 persons and
      group II consisted of 72 persons). The following studies were performed: BMI,
      serum lipids parameters and hormones estimation including gonadotropins, free and
      total testosterone, estradiol and dehydroepiandrosterone sulfate (DHEAS). A lower
      mean concentration of DHEAS, free and total testosterone and a higher frequency
      of increased gonadotropins concentrations were found in men aged 60 than aged 50.
      Moreover, positive correlation between BMI and serum total cholesterol and LDL
      level in the studied group was observed. To conclude, we can say that in men over
      50 years of age hormones examination should be performed and in case of
      insufficient hormones level adequate replacement should be instituted.

PMID- 14699689
TI  - [Bone metabolism in dialysis patient assessed by biochemical markers and
      densitometry].
AB  - A decrease in bone mineral density is common in patients with chronic renal
      failure. It is also a risk factor for fractures in this population. The aim of
      the study was to evaluate bone mineral density-BMD and some biochemical markers
      of bone metabolism in regard to the method of renal replacement therapy:
      hemodialysis or peritoneal dialysis. The studies were performed in two groups of
      patients: 2 patients maintained on chronic hemodialyses (HD) and 21 patients
      treated with chronic ambulatory peritoneal dialysis (CAPD). Bone mineral density
      was measured using dual energy X-ray absorptiometry (DEXA) in L2-L4 segments of
      lumbar spine and femoral neck. Concentrations of parathormon, osteocalcin, bone
      specific alkaline phosphatase, serum CrossLaps (degradation products of C
      terminal telopeptides of type I collagen) vitamin D3 were studied using
      commercially available kits. In femoral neck bone mineral density was
      significantly higher in CAPD patients when compared to HD, without significant
      differences in bone mineral density in lumbar spine. There was statistically
      significant correlation between BMD of the lumbar spine and time of hemodialysis
      (r = 0.39, p < 0.05). In CAPD patients BMD of lumbar spine correlated negatively
      with vitamin D3 (r = -0.54, p < 0.05), osteocalcin (r = -0.54, p < 0.05), and
      positively with body mass index-BMI (r = 0.63, p < 0.01). BMD of femoral neck
      correlated positively with BMI (r = 0.59, p < 0.01), and negatively with
      osteocalcin (r = -0.63, p < 0.05) and time on CAPD (r = -0.52, p < 0.05). On the
      basis of our finding we conclude that BMD depends on time of renal replacement
      therapy. Biochemical markers of bone metabolism poorly correlate with bone
      mineral density in dialyzed patients.

PMID- 14699690
TI  - [Role of cytogenetics in the prognosis of patients with multiple myeloma].
AB  - The aim of the study was to evaluate the clinical and prognostic significance of
      cytogenetic abnormalities in multiple myeloma patients. Cytogenetic studies were
      performed in 95 myeloma patients aged 31-82 (median 64) prior to chemotherapy.
      The GTG and CBG chromosome banding were performed and chromosomal abnormalities
      were described according to International System for Human Cytogenetic
      Nomenclature ISCN (1995). An abnormal karyotype was observed in 29% myeloma
      patients. Patients with an abnormal karyotypes showed various numerical and
      structural aberrations with hyperdiploidy in 39%, hypodiploidy in 39% and
      pseudodiploidy in 18% of patients. Monosomy of chromosome 13 was present in 29%
      of patients with an abnormal karyotype. Multiple myeloma patients with
      chromosomal abnormalities had more advanced disease than those with normal
      karyotype (82% vs 57% had stage III myeloma). beta 2-microglobulin and LDH levels
      were higher and hemoglobin level was significantly lower in patients with an
      abnormal karyotype. The plasma cell involvement of bone marrow was significantly
      higher in these patients. Overall survival was significantly shorter of patients
      with abnormal karyotypes (median 24 months vs 18 months), particularly of
      patients with monosomy of chromosome 13 (median 14 months). Cytogenetic studies
      are helpful to evaluate the prognosis and treatment options in multiple myeloma
      patients.

PMID- 14699691
TI  - [The influence of the development of diabetes mellitus in patients with chronic
      pancreatitis on exocrine pancreatic function measured by secretin-caerulein
      test].
AB  - Diabetes occurs in 20-30% of patients above forty years old with chronic
      pancreatitis (CP). The aim of the present study was to determine the relationship
      between development of diabetes mellitus in CP patients and insufficiency of
      pancreatic exocrine secretion as well as changes in composition of pancreatic
      juice. Ninety CP patients with diagnosis confirmed by endoscopic retrograde
      pancreatography (ERP) were studied. They were divided into 3 groups in dependency
      on ERP changes (according to Cambridge classification) and oral glucose tolerance
      test (OGTT): group A--equivocal or mild changes in ERP and normal OGTT (control
      group); group B--moderate or marked changes in ERP and normal OGTT: group C-
      moderate or marked changes in ERP and diabetes mellitus. The exocrine pancreatic
      function was determined by the secretin-caerulein test; volume of duodenal
      content and bicarbonate, protein, alpha-amylase activity outputs were measured.
      RESULTS: All exocrine pancreatic function parameters were diminished in B and C
      groups compared with A group--differences were statistically significant. However
      in group C values of volume and bicarbonate, protein and amylase activity were
      especially low. CONCLUSION: Exocrine pancreatic insufficiency is strongly
      associated with anatomical changes of the pancreas but also depends on endocrine
      function.

PMID- 14699692
TI  - [Treatment of heart failure: guidelines compared to clinical practice].
AB  - Last decade brought great development in the treatment of patients with heart
      failure (HF). General use of angiotensin-converting-enzyme inhibitors (ACE-I) in
      patients with asymptomatic left ventricular dysfunction or with HF significantly
      reduced morbidity and mortality. The aim of this study was to assess how the
      specialists from Cardiology Department and Gastroenterology Department think that
      heart failure should be managed, how they implement their knowledge and if it is
      consistent with the recommendation of European Society of Cardiology (ESC) and
      whether differences exists in practice between specialists. In the first phase
      the specialists, cardiologists and diabetologists, answered the questions about
      the management of different stages of HF. In second phase we analysed medical
      documentation of 345 patients aged between 38 and 98 years, hospitalised in
      Cardiology and Gastroenterology Departments from October 2000 to February 2002 by
      reason of coronary artery disease, hypertension and dilated cardiomyopathy. In
      the third phase we compared the knowledge of heart failure management from
      questionnaire and its implementation, the compliance with ESC recommendation and
      finally whether differences in clinical practice exist between cardiologist and
      diabetologists. RESULTS: ACE-I were prescribed in all NYHA classes of HF. In over
      50% patients in II NYHA class to 94% in IV NYHA class in Cardiology Department.
      Differences between the Departments in prescribing of ACE-I were observed. Beta
      blockers (BB) were used with the same frequency in all NYHA classes, more often
      in Cardiology Department. Frequency of the administration of digoxin, diuretics,
      aldosterone receptor blocker was increasing starting with II NYHA class. The
      highest compliance between declarations from questionnaire and clinical practice
      concerned the use of BB and ACE-I combination.

PMID- 14699693
TI  - [Somatostatin analogs in the treatment of carcinoid syndrome: a case report and
      review of literature].
AB  - We report the case of 48-year old patient with carcinoid syndrome successfully
      treated with somatostatin analogues. We also present the review of published
      literature about the use of somatostatin analogues in the treatment of carcinoid
      syndrome. In addition, reported case shows difficulties in access to this
      treatment, caused by economical reasons.

PMID- 14699694
TI  - [Hypopituitarism and hematological abnormalities mimicking myelodysplastic
      syndrome. Report of four cases].
AB  - Insufficiency of the pituitary gland and hematological abnormalities may coexist
      in the context of two syndromes. In the course of some hematopoietic neoplasms,
      particularly acute leukemias, the pituitary insufficiency may be caused by
      destruction of the gland either by direct neoplastic infiltration or occlusion of
      vessels. Alternatively, thy pituitary dysfunction may be associated with but not
      caused by hematological abnormalities, usually mild peripheral cytopenias. We
      present four cases of the latter type (1. M/33, pituitary tumor, hypogonadism,
      hyperprolactinemia, anemia, mild leukopenia with leukocytosis, 2. F/54, pituitary
      tumor, hyperprolactinemia, thyreotropic and corticotropic insufficiency, anemia,
      thrombocytopenia, mild neutropenia, 3. F/27, pituitary tumor, diabetes insipidus,
      hypogonadism, sideropenic anemia, leukopenia, thrombocytopenia, 4. M/24, primary
      multihormonal insufficiency of the anterior portion of the pituitary gland,
      neutropenia, microcytosis). Trephine and aspiration bone marrow biopsies revealed
      topographic and cytological abnormalities partially resembling these found in
      myelodysplastic syndromes (MDS). Bone marrow cellularity varied markedly between
      and within the cases, and in three patients abnormal aplastic areas were found.
      The percentage of hematopoietic stem cells (CD34+) was low in three cases and
      normal in one case. Pituitary dysfunction may be associated with hematological
      abnormalities simulating MDS, but showing different, less aggressive clinical
      course. The proliferative potential of hematopoietic cells is low, the peripheral
      blood abnormalities are stable, and no patient developed acute leukemia. Detailed
      bone marrow examination, including the trephine bone marrow biopsy, is useful in
      differentiation with true MDS, which was also reported in the literature in the
      patients with pituitary insufficiency.

PMID- 14699695
TI  - [A case of primary non-Hodgkin brain lymphoma].
AB  - The paper presents a rare case of primary, non-Hodgkin brain lymphoma discovered
      in 64 years old woman. Non specific symptoms conducted to misdiagnoses of
      dementia and syderopenic anaemia. The proper identification has been made after
      10 months by post-mortem histopathological analysis.

PMID- 14699696
TI  - [The role of calcium-sensing receptors in physiology, pathology and therapy].

PMID- 14699697
TI  - [Liver transplantation for hepatocellular carcinoma].

PMID- 14699698
TI  - [Liver transplantation in Budd-Chiari syndrome].

PMID- 14699699
TI  - [Diagnosis and treatment of ischemic heart disease in patients with chronic renal
      failure].

PMID- 14699700
TI  - [Angiogenesis in atherosclerosis obliterans. New therapeutic possibilities].

PMID- 14699701
TI  - [The role of mast cells in pathogenesis of selected lymphatic disease].

PMID- 14699702
TI  - Readmissions for coronary artery bypass graft surgery: an important supplementary
      outcome.

PMID- 14699703
TI  - Physical activity for cardiovascular disease prevention.

PMID- 14699704
TI  - Non-pharmacological treatment of atrial fibrillation.
AB  - In the last decade various non-pharmacological treatments for the cure of atrial
      fibrillation (AF) have been proposed. These may be divided into only palliative
      (i.e. pacing therapy or atrioventricular node ablation)--since it does not
      influence the factors favoring AF persistence--or radical with the aim to
      eliminate the factors causing AF with the goal of preventing its recurrences.
      This can be achieved either by eliminating the trigger responsible for the
      initiation or by modifying the substrate that permits the maintenance of the
      arrhythmia or both. Surgical results clearly show how, in a higher percentage of
      cases, it is possible to cure AF by modifying the substrate. Nowadays, this
      should be performed in almost every patient with permanent or paroxysmal AF who
      is submitted to heart surgery, while it is not yet time to extend this technique
      to patients with idiopathic AF. Percutaneous catheter ablation has not yet
      reached optimal results. The elimination of triggers seems to be the first step
      in patients with idiopathic lone AF; this may be accomplished by electrically
      isolating the pulmonary veins and when possible by directly eliminating
      extrapulmonary foci if present. The results of this technique were relatively
      good but still need to be improved. In case of permanent AF or in the presence of
      atrial enlargement, the removal of the triggers alone is not enough to eliminate
      the arrhythmia since the substrate anomalies seem to play a more important role
      in its maintenance than the trigger itself. Ablative therapy of AF is a technique
      that still needs further improvement before it may be considered a definite
      approach and it is still to be proposed only to selected patients with drug
      resistant and poorly tolerated AF.

PMID- 14699705
TI  - Oral anticoagulant therapy in the primary and secondary prophylaxis of stroke.
AB  - Stroke is the first cause of disability and the second cause of mortality in the
      world. Oral anticoagulants have been proved to be effective in the primary and
      secondary prophylaxis of stroke not only in cardiac conditions but also in other
      pathologies such as the antiphospholipid syndrome. Though the efficacy of oral
      anticoagulants in the prevention of stroke has been consolidated in several
      conditions such as mechanical prosthesis, atrial fibrillation, and the
      antiphospholipid syndrome, their role is less clear in patent foramen ovale,
      interatrial septal aneurysm, dilated cardiomyopathy, and aortic plaques.
      Nevertheless, oral anticoagulants have recently been re-evaluated in large
      clinical trials and have been shown to be effective in the secondary prevention
      of myocardial infarction and stroke. This review considers both the established
      and controversial aspects and the role of anticoagulation clinics in the
      practical approach to these patients, as well as their education and quality of
      life.

PMID- 14699706
TI  - Cerebral vasoconstriction in neurally mediated syncope: relationship with type of
      head-up tilt test response.
AB  - BACKGROUND: The pathophysiology of neurally mediated syncope (NMS) is unclear.
      Cerebral vasoconstriction has been observed in NMS patients during tilt testing.
      To shed light on the pathophysiology of NMS, we attempted to establish whether
      the degree of cerebral vasoconstriction changes with the tilt test positivity
      type, scored in accordance with Sutton's classification. METHODS: Twenty-one
      patients (12 males and 9 females, mean age 41 +/- 15 years) consecutively
      admitted to tilt test evaluation were studied through simultaneous recordings of
      their electrocardiogram, blood pressure, electroencephalogram and transcranial
      Doppler sonography (TCD) of the middle cerebral artery. TCD allowed computation
      of the Gosling's pulsatility index [PI = (systolic velocity--diastolic
      velocity)/mean velocity], as an index of cerebrovascular resistance. RESULTS: In
      the 13 tilt-positive patients (62%), TCD revealed a significant PI increase at
      the onset of prodromic symptoms in comparison with baseline (2.01 +/- 0.94 vs
      0.77 +/- 0.20, p < 0.001, paired-sample Student's t-test). No significant TCD
      alterations were seen in tilt-negative patients. Furthermore, the percentage
      change in the PI from baseline was significantly higher in cardioinhibitory types
      (254 +/- 51%, 5 patients) than in mixed and vasodepressor types (101 +/- 22%, 8
      patients, p < 0.001, independent-sample Student's t-test). CONCLUSIONS: Our data
      show that the degree of cerebral vasoconstriction at the onset of prodromic
      symptoms changes with the tilt test positivity type. We suggest that in NMS
      patients the degree of cerebral vasoconstriction may depend on the amount of
      sympathetic activation. The sympathetic modulation of cerebral vasoconstriction
      may therefore be a turning point in the explanation of the pathophysiology of
      NMS.

PMID- 14699707
TI  - Non-invasive assessment of the composite radial artery and in situ left internal
      thoracic artery Y-graft for myocardial revascularization.
AB  - BACKGROUND: It is controversial whether composite arterial grafts can provide
      adequate blood flow for myocardial revascularization. We assessed at
      transthoracic echography and myocardial scintigraphy the composite radial artery
      in situ left internal thoracic artery Y-graft. METHODS: In 32 of 36 consecutive
      patients who underwent myocardial revascularization using this composite arterial
      graft, successful postoperative transthoracic images of the main stem of the Y
      graft were obtained at rest and early after standard exercise. The main stem
      diameter, cross-sectional area and blood flow velocity and volume were measured.
      The coronary flow reserve (CFR) was calculated. The patients were divided into
      three groups according to the number of coronary artery systems bypassed with the
      Y-graft: group I included 11 patients with one coronary system bypassed, group II
      18 patients with two, and group III 3 patients with three coronary systems
      bypassed. In 14 patients myocardial scintigraphy was performed at rest and after
      stress. RESULTS: After exercise, the diameter, cross-sectional area, and blood
      flow velocity and volume increased. The mean CFR in group III was greater than in
      group I (p = 0.00045) and in group II (p = 0.049). In 2 patients, the nuclear
      stress test was positive (reversible ischemia in the distribution area of the Y
      graft) and the mean CFR was lower than in the patients with a negative nuclear
      stress test (p = 0.046). CONCLUSIONS: This composite arterial graft is a
      compliant conduit, able to regulate its flow capacity to myocardial demand. Non
      invasive assessment of this Y-graft using transthoracic echography is possible,
      and correlates with the results of myocardial scintigraphy.

PMID- 14699708
TI  - Treatment modalities of non-ST-elevation acute coronary syndromes in the real
      world. Results of the prospective R.OS.A.I.-2 registry.
AB  - BACKGROUND: Despite advances in the treatment of non-ST-elevation acute coronary
      syndromes (ACS) based on randomized studies and published guidelines, the extent
      to which such treatments are applied in daily clinical practice remains elusive.
      The R.OS.A.I.-2 registry was undertaken to assess the modalities of the treatment
      of non-ST-elevation ACS, both in terms of the use of drugs, with particular
      attention to glycoprotein IIb/IIIa inhibitors and clopidogrel, as well as type of
      strategy, aggressive versus conservative, in a consecutive series of patients
      admitted to 76 coronary care units (CCU) in Italy. METHODS: The R.OS.A.I.-2 study
      group consisted of 76 hospitals in 7 regions of Northern and Central Italy: 38
      centers had a CCU without cath lab facilities (type 1), whereas 38 type 2 centers
      had a CCU with an on-site interventional cath lab. Globally, 1581 patients with a
      diagnosis of non-ST-elevation ACS entered the registry during an 8-week period
      and had a 30-day follow-up. Patients were considered as being aggressively
      treated if they had coronary arteriography within 96 hours of admission, whereas
      all other patients were considered as being conservatively treated even if they
      underwent coronary arteriography after the first 96 hours of hospitalization.
      RESULTS: An aggressive approach was employed in 789 patients (50%), whereas of
      the 792 (50%) conservatively treated patients 363 had a late coronary
      arteriography at a mean of 10.5 +/- 13 days after admission. Aggressively treated
      patients were younger (p < 0.0001), had less frequently ST-segment depression (p
      = 0.04), troponin positivity (p = 0.02), elevated creatine kinase (CK) and/or CK
      MB levels within 24 hours of admission (p = 0.01), and had been more often
      admitted to type 2 hospitals (p < 0.0001) than those treated conservatively.
      Glycoprotein IIb/IIIa blockers (predominantly "small molecules") were more
      frequently used in younger patients (p = 0.04), in those treated aggressively (p
      < 0.0001), with ST-segment depression (p = 0.01), and in those with a high TIMI
      risk score (p = 0.001), whereas the use of clopidogrel did not differ in any
      patient subgroup except in patients < 70 years (p = 0.01) and in those treated
      aggressively (p < 0.0001). Percutaneous coronary interventions were performed in
      656 patients (481 in the aggressively treated group and 175 in the conservatively
      treated group). At 30 days, the death rate was 3.4% and the myocardial infarction
      rate was 5.8%. Age, ST-segment depression, elevated CK and/or CK-MB levels within
      24 hours of admission and a conservative approach were significant predictors of
      an unfavorable outcome. CONCLUSIONS: The R.OS.A.I.-2 registry confirms that the
      population admitted to the CCU with non-ST-elevation ACS has a higher risk
      profile than that included in recent clinical trials. The aggressive approach is
      still more dependent on the cath lab availability than on a risk stratification
      process. Conservatively treated patients have worse clinical features and short
      term prognosis. Applying an invasive approach to higher risk groups might further
      improve the global outcome of non-ST-elevation ACS.

PMID- 14699709
TI  - Contribution of the type 1 plasminogen activator inhibitor 4G/5G gene
      polymorphism to impaired fibrinolysis in vital exhaustion.
AB  - BACKGROUND: Inappropriate coping with chronic stress may result in a state of
      "vital exhaustion" that has been associated with coronary artery disease.
      Impaired fibrinolysis due to an increase in type 1 plasminogen activator
      inhibitor (PAI-1) might mediate this link. Genetic and environmental factors both
      regulate the plasma PAI-1 levels. We investigated the contribution of the PAI-1
      4G/5G gene polymorphism to the plasma levels of PAI-1 in exhaustion. METHODS: The
      study participants were 258 (mean age 40.9 +/- 9.1 years) apparently healthy
      subjects of an airplane manufacturing plant in Germany who completed the
      Shortened 9-item Maastricht Vital Exhaustion Questionnaire. A median split was
      performed on exhaustion scores rendering two groups of exhausted and non
      exhausted subjects. The PAI-1 4G/5G polymorphism in the promoter region of the
      PAI-1 gene and several variables related to the insulin resistance syndrome known
      to affect plasma PAI-1 levels were assessed. RESULTS: Across all subjects,
      exhausted individuals had higher PAI-1 antigen levels than non-exhausted subjects
      (46.6 +/- 20.7 vs 38.3 +/- 21.4 ng/ml, p = 0.002). There were no significant
      differences in the PAI-1 antigen levels between exhausted and non-exhausted
      individuals with both the 4G/4G and the 4G/5G polymorphism. With the 5G/5G
      polymorphism, however, exhausted subjects had higher PAI-1 antigen levels than
      non-exhausted subjects (44.9 +/- 22.9 vs 31.2 +/- 13.1 ng/ml, p = 0.017). These
      results did not change when controlling for the variables of insulin resistance.
      CONCLUSIONS: The findings suggest that the PAI-1 4G/5G gene polymorphism might
      affect the plasma PAI-1 levels related to exhaustion severity. With the 5G/5G
      polymorphism, exhausted subjects might have less fibrinolytic capacity than non
      exhausted subjects.

PMID- 14699710
TI  - Usefulness of multiplane transesophageal echocardiography in the recognition of
      artifacts and normal anatomical variants that may mimic left atrial thrombi in
      patients with atrial fibrillation.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is the method of choice for
      the evaluation of the left atrium and of left atrial appendage (LAA) thrombosis.
      However, the anatomy of the left appendage is complex and reverberations from
      anatomical structures may create images and ghosting which mimic left atrial
      thrombosis. The purpose of this study was to investigate whether a systematic
      approach through TEE may facilitate the recognition of LAA anatomical variants
      and artifacts. METHODS: One hundred and sixty-four consecutive patients scheduled
      for cardioversion of atrial fibrillation (study population) and 30 patients
      (control group) undergoing mitral valve surgery were submitted to TEE using a
      multiplane probe in order to obtain a systematic evaluation of the LAA. The
      number of LAA lobes and the presence of thrombi and artifacts were evaluated.
      RESULTS: The majority of the study patients had a bilobed (53.1%) or single-lobed
      (34.1%) LAA. Thrombi were identified in 6%. Artifacts were found in 38 cases
      (23.2%) and their position was localized precisely at a distance from the
      transducer which was twice that from the partition-bend between the left upper
      pulmonary vein and left appendage, suggesting a reverberation. No differences in
      echocardiographic parameters were found in patients with (group 1) or without
      (group 2) artifacts. Cardioversion was successful in a similar percentage of
      cases in the two groups (group 1 68%, group 2 76%) without complications. In
      controls, the percentages of a single-(33%) and bilobed (40%) left appendage were
      similar to those found in the study population. Artifacts were identified in 11
      controls (37%); no thrombi were detected during surgical left appendage
      inspection in these cases. CONCLUSIONS: A systematic approach with multiplane TEE
      facilitates the evaluation of the LAA anatomy and the recognition of artifacts,
      thus reducing the likelihood of false positive or negative diagnoses of left
      appendage thrombi.

PMID- 14699711
TI  - The San Daniele 2 Project: protocol description and population characteristics.
AB  - In 1990 we studied the prevalence and determinants of carotid atherosclerosis in
      an Italian general asymptomatic population (630 males and 718 females aged 18-99
      years) living in the San Daniele district of the Friuli-Venezia Giulia Region.
      The global prevalence of subclinical carotid atherosclerosis was 25.4% in men and
      26.4% in women. We considered intima-media thickness, non-stenotic plaque (<
      40%), and stenotic plaque (> 40%). In the multiple logistic regression, the cross
      sectional analysis of subjects aged 40 years showed a positive significant
      association between plaques/stenosis and age (p < 0.001), systolic blood pressure
      (p < 0.01), cigarette smoking (p < 0.0001), and the protective effect of high
      density lipoprotein cholesterol (p < 0.037). In 2002 we decided to re-examine the
      initial cohort with the following objectives: prospectively evaluating the
      modifications of the previous carotid findings, their relationship with known and
      less documented cardiovascular risk factors and the predictive power of those
      variations on incident coronary and cerebrovascular events. We plan to evaluate
      the association of carotid plaque and carotid intima-media thickness with the
      genetic polymorphisms involved in atherosclerosis in survivors and finally to
      study the incidence and the determinants of atrial fibrillation in a general
      population. In this paper, we will describe the methodology of the screening and
      the cohort population characteristics. We have compared the San Daniele Project
      survivor cohort's characteristics to the current general population of the same
      age living in the Friuli-Venezia Giulia Region so as to extend the study's
      conclusions to the whole regional population.

PMID- 14699712
TI  - Aortic valve: do its nervous and contractile elements have any role?
AB  - Recent knowledge on aortic valve physiology and its cellular and ultrastructural
      characteristics lead us to believe that the opening and closing mechanism is not
      only the result of the different pressures between the aorta and left ventricle
      but it is also a function of the interaction between elastic forces acting on a
      complex structure such as the valve. The latter consists of cells with muscular
      properties and of some elements capable of dynamically modifying their
      properties. These cells, which can regenerate themselves, seem to be closely
      related to nerve endings whose exact function at the valvular level is yet to be
      defined. The aim of this paper was to review the most recent literature on the
      aortic valve nervous and ultrastructural properties as they are related to the
      physiological and pathophysiological patterns.

PMID- 14699713
TI  - Single coronary artery associated with perimembranous ventricular septal defect.
AB  - The authors report the case of an adult male patient with a congenital
      ventricular septal defect who underwent an invasive assessment of his heart
      disease. Here, the septal defect was identified in the perimembranous area and a
      pulmonary-to-systemic flow ratio of 1.4:1 was calculated. At coronary
      angiography, a single coronary artery was found. This particular anomaly
      consisted of a proximal right coronary artery originating from a septal branch of
      the left anterior descending coronary artery and a distal right coronary artery
      arising from the distal left circumflex artery. Such an association constitutes
      an exceedingly rare congenital condition.

PMID- 14699714
TI  - Vasculitis mimicking bacterial endocarditis.
AB  - Fever of unknown origin is one of the most intriguing issues in clinical
      practice. One of the most feared diagnoses, especially in patients with known
      valvular disease, is endocarditis. The differential diagnosis of fever is often
      complicated by the clinical-pathological overlap between the systemic
      inflammatory response in different types of pathologies such as infectious,
      autoimmune or neoplastic disorders. We report a case of a patient presenting with
      fever, cutaneous nodules and malaise, with a known mitral valve prolapse and
      moderate regurgitation, in which the diagnosis of Wegener's granulomatosis was
      finally made.

PMID- 14699715
TI  - Parallel hierarchy of scientific studies in cardiovascular medicine.

PMID- 14699716
TI  - [Structure and functional organization of cardiology].

PMID- 14699717
TI  - ANA/UAN defend charge nurses' right to organize.

PMID- 14699719
TI  - Why aren't school nurses caring for all of Michigan's children?

PMID- 14699721
TI  - Software program designed to help hospitals control infection.

PMID- 14699720
TI  - Public health and the tobacco settlement dollars.

PMID- 14699722
TI  - How the information highway can help manage medical equipment.

PMID- 14699723
TI  - Taking the intranet plunge: create it ... maintain it ... and use it....

PMID- 14699724
TI  - An endangered species? Electronic data storage threatens the filing cabinet.

PMID- 14699725
TI  - Blurring the lines: the shifting relationship between IT and biomedical
      departments.

PMID- 14699726
TI  - Surviving the clinical-IT merger: seven tips help pave the way.

PMID- 14699727
TI  - PACS ... what is it really?

PMID- 14699728
TI  - Real-time decision support systems.

PMID- 14699729
TI  - Switching IT: troubleshooting 201.

PMID- 14699730
TI  - Information technology standards drive health care solutions.

PMID- 14699731
TI  - Take two aspirin and e-mail me in the morning.... Online communication offers
      promise to reduce cost and improve care.

PMID- 14699732
TI  - Striving for "end-to-end" knowledge to support networked medical systems.

PMID- 14699733
TI  - Seeing both worlds ... from CE to IT.

PMID- 14699734
TI  - Salary survey: benchmarking your employment information.

PMID- 14699735
TI  - Measured effects of user and clinical engineer training using a queuing model.
AB  - This article puts forward a new proposal to calculate count, turnaround,
      response, and service time of work orders in a clinical engineering (CE)
      department. These are calculated by means of a queuing model as a measurement
      tool. This proposal was tested in a 600-bed hospital with an inventory of 1094
      medical devices and with 6 full-time clinical engineers. In April 1999, a
      simulation (with ARENA 3.01 developed by System Modeling Corporation) of the
      working of this proposal was performed with desired values being applied to the
      queuing model. At the end of 2002, real work order data from the database was
      recorded. As predicted, the results showed that all the indicators of
      nonscheduled work orders decreased. Response and turnaround time were reduced
      from 27 to 0.56 hours and 27.48 to 1.13 hours, respectively. From a backlog of 22
      outstanding repair orders per month between April 1999 and January 2000, the
      number was reduced to 4 in December 2002. The queuing model also helped to
      measure the positive effects on arrival and service rates when users and CE were
      trained. The difference between simulated and real values was under 5%.

PMID- 14699736
TI  - An electrophoretic method to deliver topical drugs to the eye.
AB  - It is possible that many patients avoid complete ophthalmic exams because pupil
      dilation is slow, reversal sluggish, and vision blurred. Others experience
      incomplete dilation during exams or prior to surgery when good dilation is
      essential to successful outcome. Iontophoresis, the application of low-level
      electrical current to promote traversal of desired molecules across a boundary,
      has been used for many years and has recently become common in transdermal drug
      delivery. We now investigate iontophoresis as a method of accelerating drug
      absorption into the ocular anterior segment. In vivo rabbit studies assessed
      iontophoresis effects on the performance of dilators and constrictors. 1-mA and 4
      mA direct current levels applied for 2-minute durations yielded dilation time
      history measurements. Subsequent in vitro tests at a wide range of current
      densities showed minimal chemical modifications in ocular pharmaceuticals. Drug
      samples processed through high-performance liquid chromatography (HPLC)
      pinpointed minimal structural changes. Detailed in vivo rabbit testing is under
      way. Using 2 dilators and constrictors in crossed testing with 0.5-mA to 1.25-mA
      current levels and 20-sec to 60-sec durations, we recorded dilation progress by
      digital photography. Initial studies showed faster, larger dilations and quicker
      reversal using iontophoresis. Drug testing showed chemical structures remaining
      constant for clinically useful current levels, < or = 1 mA (< or = 1.25 mA/cm2
      current density). Drug pH and HPLC retention times were constant within this
      range, and resistivity varied linearly as expected for increasing current. Rabbit
      testing will quantify improved drug speed and efficacy, validate the charge
      delivery electrode design, and indicate iontophoretic current and duration for
      further use. Tested ocular drugs showed no degradation when exposed to clinically
      useful iontophoretic currents. Preliminary results indicate significant time
      reductions for dilation and reversal, plus increases in maximum dilation. This
      procedure may aid clinicians by allowing more rapid complete examinations and
      surgical preparations for patients. Making dilation more convenient will also
      improve patient acceptance of exams, aiding earlier detection and treatment of
      ocular disease.

PMID- 14699737
TI  - A simple method of equipment replacement planning.

PMID- 14699738
TI  - Ban or bandwidth? Has your hospital changed its cell phone policy?

PMID- 14699739
TI  - The fundamentals of ... positron emission tomography (PET).

PMID- 14699740
TI  - POTS to broadband ... cable modems.
AB  - There have been 3 columns talking about broadband communications and now at the
      very end when it's time to compare using a telco or cableco, I'm asking does it
      really matter? So what if I can actually get the whole 30 Mbps with a cable
      network when the website I'm connecting to is running on an ISDN line at 128
      Kbps? Broadband offers a lot more bandwidth than the connections many Internet
      servers have today. Except for the biggest websites, many servers connect to the
      Internet with a switched 56-Kbps, ISDN, or fractional T1 line. Even with the big
      websites, my home network only runs a 10 Mbps Ethernet connection to my cable
      modem. Maybe it doesn't matter that the cable lines are shared or that I can only
      get 8 Mbps from an ADSL line. Maybe the ISP that I use has a T1 line connection
      to the Internet so my new ADSL modem has a fatter pipe than my provider! (See
      table 1). It all makes me wonder what's in store for us in the future. PC
      technology has increased exponentially in the last 10 years with super fast
      processor speeds, hard disks of hundreds of gigabytes, and amazing video and
      audio. Internet connection speeds have failed to keep the same pace. Instead of
      hundreds of times better or faster--modem speeds are barely 10 times faster.
      Broadband connections offer some additional speed but still not comparable growth
      as broadband connections are still in their infancy. Rather than trying to make
      use of existing communication paths, maybe we need a massive infrastructure
      makeover of something new. How about national wireless access points so we can
      connect anywhere, anytime? To use the latest and fastest wireless technology you
      will simply need to buy another $9.95 WLAN card or download the latest super
      slick WLAN compression/encryption software. Perhaps it is time for a massive
      infra-restructuring. Consider the past massive infrastructure efforts. The telcos
      needed to put in their wiring infrastructure starting in the 1870s before
      telephones were useful to the masses. CATV was a minor player in the TV broadcast
      business before they installed their cabling infrastructure and went national.
      Even automobiles were fairly useless until roads were paved and the highway
      infrastructure was built!

PMID- 14699742
TI  - Microbial lethality: when it is log-linear and when it is not.

PMID- 14699741
TI  - Engineers and technologists can aid in improving device design.

PMID- 14699743
TI  - Sharing the knowledge ... tips on preparing continuing practice journals.

PMID- 14699744
TI  - Paving a smooth road to relocation: tips on how to make the transition to a job
      out-of-state.

PMID- 14699745
TI  - [Developing a sustainability network for the implementation of National
      Curricular Guidelines of the Graduation Course in Nursing].

PMID- 14699746
TI  - [Curricular guidelines and pedagogical projects: starting a reflection].
AB  - This text presents some reflections which we intend to use as subsidies for
      discussions stemming from the need to implement the current Curricular Guidelines
      in undergraduate Nursing programs in Brazil. Having as a reference authors who
      write from a post-critic perspective in Education, the text proposes a change in
      focus to address these reflections, namely, answers to questions, from certainty
      to doubt, from prescription to problematization. Following this line, we suggest
      that curricular guidelines should aim at providing references for the creation of
      political-pedagogical projects which articulate both with the political and
      social demands of the broad-based society as to local needs and interests,
      without attaching to or submitting to them.

PMID- 14699747
TI  - [Curricular guidelines and pedagogical projects: starting a reflection --comments
      on the text].
AB  - This text dwells on ideas stemming from reflections found in the base article of
      the debate section about national curricular guidelines, namely,
      interdisciplinary ideas, ideas of a curriculum taken as a product and producer of
      culture and identity and the emergence of the notion of competence. As a result
      of this discussion, it signals that there is no way to deny that learning is
      coded by discipline and curriculum, that it organizes itself within time and
      space, and that it becomes a cultural basis for an area of knowledge. Its
      conclusion suggests that nurses/teachers should ask themselves which abilities
      they need to acquire as teachers, in order to meet the requirements of this
      pedagogical praxis.

PMID- 14699748
TI  - [Paths to nursing education: continuity or rupture?].
AB  - Some reflections are presented about the current trends in Nursing Education in
      face of Curricular Guidelines for Undergraduate Programs in Nursing, aiming at
      providing subsidies for changes in Higher Education. It is primarily geared to
      discussing nurse education, focusing on the development of the competencies
      needed to change the present health care delivery model and to working in
      multiprofessional teams, aiming at the consolidation of the Public Health System
      (SUS--Servico Unico de Saude) in Brazil.

PMID- 14699749
TI  - [Curricular guidelines and promotion of conditions for change in nursing
      training].
AB  - This text analyzes the article "Curricular Guidelines and Pedagogical Projects",
      an object for discussion in this REBEn's (Brazilian Review of Nursing) section.
      The authors expose their opinion as to the complexity of this theme and highlight
      two points coming out of this debate--the issue of the reproduction-
      problematization opposition in respect to curricular reform, and the content of
      curricular projects aiming at changes in nurse education. The author concentrates
      her analysis on the curricular guidelines and changes, beyond the text, by
      highlighting the great importance of national policies of investment to guarantee
      favorable conditions for the necessary curricular changes. She parallels the
      educational to the health sector in order to assess the creation of curricular
      guidelines, and outlines strategies for their implementation. She stresses the
      notion of competencies as possibilities to give rise to a new kind of worker, by
      strengthening the issue of social responsibility placed upon education for the
      constitution of citizens. The importance placed on educators qualification is
      discussed when talking about competencies development, besides the investment on
      a new professional ethics, as well as our difficulty for going beyond
      preestablished notions, in such a way that favorable strategies are generated for
      developing self-criticism and professional responsibility.

PMID- 14699750
TI  - [Curricular guidelines and pedagogical projects: it is time for action!].
AB  - This text points out the analytical content of the article "Curricular Guidelines
      and pedagogical projects", which opens the debate section at REBEn (Brazilian
      Review of Nursing). It criticizes its provisional character and the fact that it
      is not propositional. It provides comments from the authors regarding the design
      of guidelines and their context, giving opinions about their content when it
      comes to health professionals education. Throughout their text, the authors
      express their agreement with the manner in which the National Curricular
      Guidelines have been built in Brazil, stressing the political context they are to
      be included in when being interpreted and inside which they are supposedly going
      to be implemented.

PMID- 14699751
TI  - [New graduate program at UNISINOS: sharing the experience of a pedagogical act].
AB  - In this article we present the process of creation of an innovative proposal for
      undergraduate teaching, developed by an interdisciplinary group at "Universidade
      do Vale do Rio dos Sinos--UNISINOS". Besides pointing out the theoretical
      epistemological referential supporting this proposal, we will also be discussing
      the implications some paradigm ruptures have brought to the educational process
      presently being used at this University. We would like to introduce the reader to
      the process behind this way of understanding and living the educational practice,
      as well as to follow the account of an experience a group of teachers has had,
      when confronted with the task of pondering a new undergraduate program.

PMID- 14699752
TI  - [Reflections on a pedagogical praxis based on educational references and
      guidelines for nursing training].
AB  - This text aims at supplying elements for reflection on Nursing education,
      considering the introduction of national curricular guidelines and the need for
      the creation of political-pedagogical projects in undergraduate programs. By
      taking as a reference some constituent factors of the pedagogical praxis, it
      searches to raise critical thinking on this field, on the bases and the plan for
      pedagogical action, as well as the relationship between theory and practice and
      the roles of the individuals involved in a teaching-learning process.

PMID- 14699753
TI  - [Nursing curricula in Brazil and guidelines -- new perspectives].
AB  - This bibliographic clipping is aimed at presenting the history of current
      undergraduate nursing curricula, starting with the first school that came into
      existence in Brazil--"Escola de Enfermelros e enfermeiras do Rio de Janeiro", in
      1890, until the Administrative Act CNE/CES, from March/2001, a document that
      established a new curriculum for nursing education in our country. I have noticed
      that the changes in the curricula were obligatory, and now I notice that
      participation of nurses and a stronger collective interest has evolved, and they
      seem to be engaged in educating more humanized, reflexive, and critical nurses
      for the future.

PMID- 14699754
TI  - [Nursing teaching in times of change].
AB  - This paper is a reflection on the teaching of nursing in Brazil. Our main goal is
      to trace it from 1923 to 2003, trying to identify any changes occurred and the
      direction the nursing education process has taken over this time frame. Our
      analysis concentrates mainly on recent decades (eighties and nineties), a period
      when the country's redemocratization process was undertaken and a wide debate on
      the health and educational fields was initiated. It focuses on the Sanitation
      Reform Movement in Brazil and on its contribution to the training or health
      professionals and nursing teachers. As of that period, a wide discussion has been
      going on among professors, students, service nurses, and other individuals, in an
      effort to build a political-pedagogical project that would stand out as a
      political accomplishment for the nurse profession. The collective efforts seen
      during this process surpass all the changes in the history of nursing teaching,
      because of the social relevance of its conceptual frameworks, as well as due to
      the effective participation of all actors involved in the educational process.

PMID- 14699755
TI  - [Evaluation and design of a political-pedagogical project for nursing
      undergraduate programs].
AB  - This work presents the results of an experience which aimed primarily at the
      evaluation of the Political-Pedagogical Project--PPP of the nursing undergraduate
      program from UNIOESTE (Cascavel town Campus) and at pondering on a new curricular
      proposal for that program. Thus, a research project was designed to be used by
      all professors teaching that program, with the participation of students, former
      students, and professionals working on the health care delivery network, where
      field work can be carried out through practical activities and training periods
      for the students. The data gathered by them have been used as subsidies for a
      proposal to build a new political-pedagogical project, that was took effect in
      the year 2003. Besides designing a new pedagogical proposal, strategies for a
      continued evaluation of the PPP implantation process have been defined. This
      evaluation is to be performed at the end of each term.

PMID- 14699756
TI  - [Design of a pedagogical project: collective experience].
AB  - This study describes the ongoing experience to reform the pedagogical project of
      the undergraduate nursing program from Federal University of Ceara, based on the
      curricular guidelines approved by CNE/CE,S in 2001. It exposes the process of
      compliance the professors and students had to go through in order to abide by the
      proposal introduced by LDB/96 (Basic Guidelines Law/95), as well as the different
      stages needed to build referential, conceptual, and philosophical landmarks. The
      difficulties experienced relate to a poor commitment of professors to this
      process, due to the peculiar situation of the program: many professors retiring;
      a high number of substitute professors under provisional circumstances, which
      refrained them from long-term commitment. The adoption of a political-pedagogical
      project aimed at a reform of nursing teaching cannot occur in this situation.

PMID- 14699757
TI  - [Building sensitive knowledge in mental health].
AB  - This is a report of an experience presented by the faculty of the subarea
      Promoting and Recovering Mental Health, by the Nursing School, from State
      University of Rio de Janeiro, Brazil. This subarea is offered in eight of the
      total nine terms of the undergraduate program, integrating into the themes of
      other subareas at each term. Based on students' experiences regarding those
      themes, and connecting them to theory later on, we hope they will grow on
      sensitiveness and empathy, thus strengthening their role of carers for clients in
      different fields. The evaluation of this subarea points out to the qualitative
      change in the teaching/learning process.

PMID- 14699758
TI  - [Integrated curriculum of the State University of Rio de Janeiro (UERJ) Nursing
      School: reflection on human resource training for the Brazilian public health
      system (SUS)].
AB  - This work is an exploratory study, with a qualitative approach, based on a case
      study systematics, whose object is to analyze nursing professionals education
      taking into account the curriculum from FENF/UERJ. The site chosen for the
      research was the Nursing School from State University of Rio of Janeiro. The
      objectives outlined were: (a) investigate the history of creation of the
      integrated curriculum from FENF/UERJ; (b) compare the innovative proposal from
      FENF/UERJ and the proposal for human resources education made by the Public
      Health Care System in Brazil (SUS). Given the analysis of documents and the
      bibliographic review, an integrated teaching proposal was elicited, which meets
      the demands of the professional profile desired by SUS, besides being committed
      to educate a critical student, who is politically active and able to spot
      problematic situations and to strive and resolve them, according to strict
      technical and scientific patterns.

PMID- 14699759
TI  - [Nursing course of the State University of Ceara -- history and current political
      pedagogical project].
AB  - This paper describes important moments along the route of the Nursing Program at
      State University of Ceara and their influences on their current process of
      professional education. It outlines their program, their professors and students,
      as well as their political-pedagogical project. Finally, it highlights the
      importance of this instrument to warrant professional qualification.

PMID- 14699760
TI  - [Nursing for indigenous people: applying curricular guidelines].
AB  - Report on the Curricular Internship II in a Rural Indian Community, performed by
      students of the Nursing program from Manaus Nursing School--Federal University of
      Amazonas, carried out from October through December, 2002. It provided students
      with an opportunity to understand the health-disease process in Indian areas and
      to make nursing interventions. The training period was divided into three phases:
      a preparatory week, including meetings and lectures with the team delivering
      health care to Indian populations, and a seminar/report on the activities
      performed. Students reported that nurses need to have anthropological,
      ecological, and social knowledge in order to understand the health-disease
      process. This internship period provides emancipatory education, centered around
      a kind of regional reality, and follows recommendations established in current
      curricular guidelines, by favoring a teaching practice focused on local
      realities.

PMID- 14699761
TI  - [Strategies for the implementation of a new pedagogical proposal at the Nursing
      School of the Federal University of Bahia].
AB  - This article reflects on the process of designing the Pedagogical Project for the
      Nursing School from Federal University of Bahia. The socialization of this
      experience intends to contribute with other nursing institutions which, in order
      to meet new curricular requirements (DCENF--National Curricular Guidelines for
      Nursing, Medicine, and Nutrition Undergraduate Programs), are going to experience
      similar processes or which are presently going through the same process. This
      article includes some historical features and the legal basis for changes, by
      presenting the reasons for the current proposal, as well as its curricular
      organization, the main challenges and some strategies for overcoming them.
      Although some aspects which still need further attention from the faculty are
      presented, such as interdisciplinary program contents, academic management, the
      evaluation process and the implementation of the proposal, the authors come to
      the conclusion that this debate is to be continued. As this process is a dynamic
      one and is still under construction, other challenges might come up that demand
      the use of new strategies for their (re)orientation.

PMID- 14699762
TI  - [Nursing training and the strategy of integrated management of childhood
      prevalent illnesses].
AB  - The Integrated Management of Childhood Illnesses (IMCI) strategy aims at
      improving the quality of care delivered and children's health conditions. This
      article presents a description and reflection on the introduction of the
      Integrated Management of Childhood Illnesses in the Nursing undergraduate
      curriculum, based on the literature and on the experience of the authors teaching
      at the Nursing program on Children's Health from University of Sao Paulo (Nursing
      School and Nursing School from Ribeirao Preto). The authors mention historical
      aspects regarding the IMCI in Brazil and the principles that guide it. In the
      end, they indicate the potentials regarding the application of this strategy at
      the health care units for children, focusing on nurses' performance.

PMID- 14699763
TI  - [Curricular integration in nursing undergraduate programs].
AB  - This paper discusses a few lessons drawn from the curricular reform process, in
      which integration is a major challenge. The main transformations and problems
      arising from the concept of an integrated education system are approached. We
      have noticed that coping with daily problems, recognizing the existing diversity
      among individuals and power sharing are the main challenges to be conquered for
      the adoption of an integrated curriculum.

PMID- 14699764
TI  - [Participation in the design of a political pedagogical project in nursing].
AB  - This paper reports an experience tracing the route of the academic community
      pursuing a Nursing Degree at Federal University of Santa Maria, while designing
      their Political-Pedegogical Project. The methodology used for creating this
      project was the promotion of seminars, which brought together professors,
      students, civil servants, and nurses who work in practice classes and supervised
      internships. For the organization of the project, referential, conceptual, and
      structural landmarks have been used, adapted from Saupe and Alves. This nursing
      undergraduate program is on the process of designing its framework, and is
      planning on seminars to discuss teaching methodology, besides designing a follow
      up and evaluation plan for the implementation of their Political Pedagogic
      Project, as well as for the improvement of faculty competency.

PMID- 14699765
TI  - [Research at the nursing undergraduate level: requirement for completion of the
      course].
AB  - This text presents guidelines for the implementation of an Undergraduate Final
      Year Project (UFYP) in the Nursing undergraduate program from Federal University
      Center of Alfenas--MG, presenting the hardships and the results of the first four
      years, using registers found in the proceedings of the Nursing Department and
      School and the authors' experience as coordinators of this process. There were
      reports considering some features as facilitators: incentive to multidisciplinary
      work, increased number of partnerships with professionals in the field; better
      use of IT resources, of the library and database; increased participation in
      research events. And, on the difficult side we found: the establishment of norms
      for the presentation of scientific papers, since at the time the School had no
      norms for that. We came to the conclusion that, in spite of the difficulties
      found, research might take place, and it constitutes a dynamic process where
      there is a learning to learn situation, either for students or for the faculty.

PMID- 14699766
TI  - [The changing process in nursing education at the uni settings: potentials and
      challenges].
AB  - This study analyzes changes occurred in the nursing teaching and learning process
      from Brazilian Schools which pursue the UNI Project, by describing a movement
      toward change, besides resistance, conflicts, and current challenges involved. It
      is a qualitative study whose data were gathered by using Focal Groups and
      documents available in these institutions. Its results show there is a gradual,
      dynamic and continuous movement toward change, through the search for teaching
      models that might replace technical rationality with a critical-reflexive
      proposal. In spite of challenges related to evaluation and individual
      competencies to overcome resistance and conflicts, we have found that the change
      process was supported by the creation of participative spaces and horizontal
      relationships, allowing for a renewed valorization of nursing education.

PMID- 14699767
TI  - [Rethinking the teaching major in nursing under current curricular guidelines].
AB  - This is a report about the design of a curricular proposal for the Teaching Major
      in Nursing from Federal University of Rio Grande do Sul (UFRGS). In this article,
      we present a brief history line of this undergraduate program, its current
      curricular structure at UFRGS, as well as existing legislation both at its
      educational and nursing levels. Finally, the results of studies carried out by
      the Teaching Majors Coordination (COORLICEN) at UFRGS are reported, besides a
      proposal for curricular changes to the nursing major, according to the National
      Curricular Guidelines for Teacher Education and legislation pertaining to this
      profession.

PMID- 14699768
TI  - [Mental health as interdisciplinary topic in the nursing curriculum].
AB  - Our aim in this study was to check if the contents of the mental health subject
      area may permeate the courses forming the Undergraduate program in nursing, by
      describing the experience developed in a public university and by getting to know
      what the academics' perception of that practice was. Twenty-seven students took
      part in the research. A questionnaire was used. Concerning the introduction of
      the mental health subject area in other disciplines, 18.5% of the respondents
      claimed it was great, 70.5% said it was good, and 11% considered it as regular.
      As to its applicability, 7.5% got to use what they had learned, 81.5% used it
      sometimes, but they believe it is of use, and 11% of the respondents didn't get
      to use it, but believe it can be used. The application of the mental health
      subject area contents to several courses in the nursing program is perceived by
      students as a basis for a global health care to be supplied to customers, family,
      and community.

PMID- 14699769
TI  - [Interdisciplinary education for health: planning nurse undergraduate programs].
AB  - Interdisciplinary teaching as an educational alternative which allows for global
      education of individuals who are also professionals is shown in this article as
      an educational planning report organized by the undergraduate Nursing program
      from Regional University of Blumenau (FURB), located in the city of Blumenau, in
      the state of Santa Catarina, Brazil. We show this didactic-pedagogical
      perspective from a theoretical perspective that presents ethics as an alternative
      for an education process aimed at the global community. This is a didactic
      proceeding supported by the methodology of "culture circles", proposed by Paulo
      Freire. Through them one searches for the integration of relevant contents to a
      nurse training centered on essential principles, cognitive bases, and relevant
      themes.

PMID- 14699770
TI  - [Citizenship and ethics as guidelines in nurse education].
AB  - Based on our experience as Nursing Professors, we wish, by means of this
      reflection, to urge a discussion on nursing professional training, following
      guidelines as Ethics, Human Rights, and Citizenship. We understand health is a
      human value which elicits further values, and the challenges we face in this area
      are not of a moral kind, like choosing between good and evil--they are ethical
      dilemmas, stemming from the wide range of contradictory imperatives that are at
      stake within this scenario. It is paramount, therefore, to promote the
      professional training of competent nurses so that they can think critically about
      fundamental issues arising in their daily practice, and act according to ethics
      and citizenship values.

PMID- 14699771
TI  - [Health professional competencies in relation to essential public health
      functions: contribution to the design of pedagogical projects in nursing].
AB  - The development of competencies among health professionals in relation to the
      Essential Public Health Functions (EPHF) is part of a number of initiatives that
      are meant to face the need for services that can lead to the resolution of health
      problems, considering the transformations occurred in the health sector and in
      the workplace. This article's objective is to make a theoretical reflection on
      the theme of professional competencies, so that we can contribute to the
      development of political-pedagogical projects for health training and primarily
      for nursing training. For that matter, we introduce the competency-based model.
      These competencies are in accordance with the EPHF and with the competencies
      proposed so far, and are aimed at contributing to the development of
      interdisciplinary, critical, and reflexive education models.

PMID- 14699772
TI  - [Creativity and the pedagogical relationship: in search of new paths to the
      training of creative and critical professionals].
AB  - This study is a philosophical reflection and stresses the importance of freedom
      spaces inside the pedagogical relationship as a tool for the constitution of a
      critical and creative professional. We view the teaching "art" in the educational
      work as a possibility for freedom, with projects arising from the objectives
      established within his/her contextualized reality. It is paramount to value the
      intersection space as a privileged space for freedom and autonomy to be
      expressed, where the pedagogical relationship favors a practical and though
      provoking learning, rescuing the creative potential of individuals and their self
      guidance.

PMID- 14699773
TI  - [Distance education: use of the WebCT as a support tool for teaching intravenous
      therapy in nursing undergraduate programs].
AB  - This investigation focused on a learning environment via internet, through which
      Intravenous Therapy (IVT) was taught. Due to its complexity, Intravenous Therapy
      was chosen against numerous subjects to be taught through an e-learning
      environment, by comprising both technical procedures and conceptual aspects that
      can be discussed through a virtual learning environment. The objectives of this
      study were to develop educational material about Intravenous Therapy to guide
      students through the learning related to intravenous therapy, to have the related
      educational material evaluated by experts, and to evaluate the students' use of
      this material, considering difficulties and/or advantages,
      participation/interaction in this environment, and usability of its tools. The
      interface used for the internet-based training program was WebCT.

PMID- 14699774
TI  - [Competency-based training for nurses: alternation between theory and practice,
      professionalization, and complex thought].
AB  - This study aims at eliciting a reflection on a competency-based education for
      nurses by understanding alternation as a necessary condition for an articulation
      between theory and practice, as well as at discussing some issues related to
      competency-based education and professionalization. We have searched to widen up
      our understanding of what competencies are and of an articulation between theory
      and practice. We have discussed the notion of professionalization and some ways
      of working on competencies by following different approaches and distinctive
      objectives, and we have reached an understanding about competencies, how to act
      in some situations, what leads to educational commitment, and what calls for
      contextualized and complex thought. Finally, we suggest alternation as a device
      for professional nurse education.

PMID- 14699775
TI  - [What will our future look like? Answer, if you can! Perspectives from nursing
      students about their professional future].
AB  - This is a qualitative study aimed at: identifying significant factors in nurse
      education; presenting a nurse profile as perceived by an undergraduate student;
      getting to know the perspectives nursing students have for their future
      professional lives. The interviewees were twelve students in nursing
      undergraduate programs from three universities located in the state of
      Pernambuco, Brazil. Recorded interviews and non-systematic observation were
      carried out between March and April, 2003. The following categories were
      identified: choice of the nurse profession; involvement in professional
      education; reflections on academic education and perspectives for future
      professional lives.

PMID- 14699776
TI  - [Multiple sclerosis. Current aspects of the disease and treatment].

PMID- 14699777
TI  - [Bisphosphonates in oncology].

PMID- 14699778
TI  - [New therapeutic options for smoking cessation. Nicotine polacrilex tablets for
      tobacco cessation].

PMID- 14699779
TI  - [Nutrition therapy for cancer].

PMID- 14699780
TI  - [Who should get an influenza vaccination?].

PMID- 14699781
TI  - [Rational diagnostic approach in hypertension].
AB  - The list of causes of hypertension is quite long. However, the diagnostic
      procedure for detection of such forms should take in account the fact that the
      cause of nearly 95% of the cases with high blood pressure is unknown, i.e.
      primary or essential. The most often form of secondary hypertension is seen in
      patients with chronic renal disease, whereas renovascular, endocrine,
      cardiovascular or neurologic disorders all show a prevalence of less than 1%.
      Careful anamnestic evaluation and clinical examination combined with few simple
      laboratory tests allow the detection of most cases with secondary hypertension.
      Diagnosis of renovascular hypertension may require a more expended work up which,
      however, should only be performed in case of clinical suspect. Furthermore, the
      procedure in case of suspected endocrine disorders is of high clinical relevance,
      since hormonal analysis and/or radiologic examinations may be very expensive.

PMID- 14699782
TI  - [Nutritional issues in hypertension: useful or useless?].
AB  - In view of the very efficient pharmacological therapy of hypertension the
      nonpharmacological strategies are nearly forgotten. Many nutritional strategies
      are known to reduce blood pressure. In the past single strategies have been
      implemented with variable success. Salt restriction leads to lowering of blood
      pressure in salt sensitive individuals. In daily practice the restriction of salt
      is still the top priority. However, salt restriction alone is often not
      successful. A change in the whole dietary pattern, i.e. a reasonable restriction
      of salt intake in combination with an increased potassium intake from food as
      well as control of body weight has a much higher potential for blood pressure
      reduction. Potassium rich food is usually low in sodium, in addition potassium
      has favorable effects on sodium handling (e.g. natriuretic effect of potassium).
      In addition it is easier to implement a moderate sodium restriction in
      combination with a higher potassium intake (i.e. a diet rich in fruits and
      vegetables). Future strategies should focus on a global moderate change in the
      diet and life style pattern.

PMID- 14699783
TI  - [Sports and hypertension].

PMID- 14699784
TI  - [Dysphagia and odynophagia in a young adult].

PMID- 14699785
TI  - [Dilemma of early drug intervention in prepsychotic illnesses of adolescence].
AB  - It will be largely supposed that early intervention in schizophrenia improves the
      outcome of the illness. The paper summarizes the up today significant knowledge
      about the early recognition and treatment of schizophrenic psychosis in the
      adolescence. It will be pointed at the diagnostic difficulties and peculiarities
      in this age group. A comprehensive repeated assessment is necessary if prodromal
      symptoms of schizophrenia respectively psychotic states have to be taken in
      account. It will be pleaded for a early low dosis therapy with atypical
      neuroleptics to prevent the "psychotic catastrophe", that means the full outbreak
      of the disease. The pharmacotherapy should be a part of an intensive multimodal
      treatment program. The longstanding continuity of the relations to one and the
      same treatment setting and therapist responsible for it seems to influence the
      outcome positively.

PMID- 14699786
TI  - [Involving parents in child psychoanalytic psychotherapy].
AB  - Contacts with parents or other care giving persons accompanying child
      psychotherapy necessarily result from the emotional and material dependency of
      the child or adolescent. The professional guidelines for the therapeutic work
      with parents are contradictory and confusing. Experts' concepts are complex and
      inconsistent. Considering the immense impact of environmental influences on the
      development of children and adolescents a precise conceptualisation of this
      elementary part of therapy is needed in order to be able to influence the
      parental involvement in the disorder of the child. Three different kinds of
      parental involvement may be differentiated: 1. parental misunderstanding about
      what is beneficial for the development of the child, 2. parental involvement
      resulting from unconscious conflicts and 3. disturbances resulting from
      structural immaturity of the care giving persons. In regard of these different
      forms of parental involvement therapeutic aims and options for interventions are
      delineated.

PMID- 14699787
TI  - [Reflections on enuresis nocturna from the systematic perspective].
AB  - The aim of this paper is to develop a few ideas on the etiology of enuresis
      nocturna from a systemic point of view. Based on twenty single case studies a
      typology of the function of enuresis will be described by a detailed analysis of
      two case studies. The presentation is preceded by a brief summary of the present
      research situation concerning the etiology of enuresis.

PMID- 14699788
TI  - [Child psychiatric documentation in child visitation and custody disputes-
      results of a survey].
AB  - In the last decade, increasing divorce rates, a joint custodial concept, and a
      deficient legal situation of non-married fathers have been involuntarily
      provoking cases of a parent with child custody alienating that child in order to
      exclude the other parent from visitations and educational participation. Medical
      certificates are frequently of fateful importance in child custody litigation. In
      an mail survey conduced in six German cities, N = 133 child psychiatrists were
      asked about the frequency in which they issue such certificates, what
      certificates contained, what recommendations were made, and where possible the
      reasons why the other parent was not included in the diagnostic process.
      According to the results 74.4% of those surveyed were asked to issue such medical
      certificates at least once in the year prior to the survey; 42% of the
      psychiatrists stating that the other parent never or only sometimes participated.
      The symptoms most frequently certified were behavioural disorders (46%),
      aggression (34%), problems in school/ADD (28%), anxiety (26%), bed-wetting (23%),
      depression (21%), and psychosomatic reactions (20%). Outlining the
      characteristics of alienated children and of alienating parents, of "natural" and
      of "induced" stress-symptoms in children after parental separation, the article
      provides physicians and institutions of the health system with support to prevent
      medical certificates being abused in child custody litigation. Some fundamental
      guidelines are presented as to what aspects and should be explored and which
      persons referred to before certificates are issued to parents, social workers or
      judges of family law courts.

PMID- 14699789
TI  - Chemokine roles in immunoregulation and disease. Workshop proceedings, 2002.

PMID- 14699790
TI  - Introduction to chemokines and chemokine antagonists.

PMID- 14699791
TI  - Chemokine influences on adaptive immunity and malignancies of the immune system.

PMID- 14699792
TI  - Chemokines as plurifunctional mediators in the CNS: implications for the
      pathogenesis of stroke.

PMID- 14699793
TI  - Chemokines and cancer.

PMID- 14699794
TI  - Preliminary observations on CC chemokine receptor expression by mononuclear
      phagocytes in multiple sclerosis lesions: effect of lesion heterogeneity.

PMID- 14699795
TI  - Chemokines and inflammatory skin diseases.
AB  - Accumulating evidence indicates that chronically relapsing inflammatory skin
      diseases such as atopic dermatitis and psoriasis are T cell-mediated diseases.
      Thus, understanding the underlying mechanisms of memory T-cell homing to the skin
      may provide promising targets for the development of novel therapeutics to
      interfere with inflammatory processes of the skin. Chemokines, a superfamily of
      small cytokine-like, chemotactic proteins, have recently been shown to critically
      regulate leukocyte trafficking. Here we summarize results of recent studies
      associating chemokines with a psoriatic or atopic dermatitis phenotype and
      delineating their role in the recruitment of memory T cells to the skin.

PMID- 14699796
TI  - Regulation of eosinophil trafficking in asthma and allergy.

PMID- 14699797
TI  - Chemokine structure and receptor interactions.

PMID- 14699799
TI  - [To improve quality of life through early diagnosis and patient education. Your
      patient has COPD -- experts].

PMID- 14699798
TI  - Functional expression of CXCR4 in S. cerevisiae: development of tools for
      mechanistic and pharmacologic studies.

PMID- 14699800
TI  - [Can it be myocardial infarct? Atrial fibrillation in an 18-year-old patient].

PMID- 14699801
TI  - [When social contacts become a challenge. Simply, only shy or already sick?].

PMID- 14699802
TI  - [Vaccination needed by over 50-year-old persons].
AB  - Adults also need to be vaccinated against infectious diseases. Standard
      vaccinations in adulthood include those against diphtheria, tetanus and polio --
      but also catch-up vaccinations against measles, mumps and rubella are necessary.
      Special vaccinations are restricted to certain groups of persons. For the
      elderly, vaccinations against influenza and pneumococcal infections are of
      particular importance.

PMID- 14699803
TI  - [Relevant vaccination for travellers].

PMID- 14699804
TI  - [Special forms of depression: "endogenous" and "reactive"].

PMID- 14699805
TI  - [Early death of the stronger sex. Could behavior change influence men's fate].
AB  - Life expectancy in men is approximately 6.5 years shorter than in women. As an
      explanation for this difference, isolated consideration of the higher prevalence
      of coronary heart disease and cancer in men is inadequate. But it would also
      appear erroneous to postulate that differences in male and female thinking and
      behavior patterns in regard to health-risk behavior are subject to controllable
      socialization processes and "rational" realizations. The interaction of genetic
      and environmental risk factors and socialization is largely unknown. A sex
      specific consideration of risk behavior and quality of life suggest that a
      healthy lifestyle, relevant information and preventive measures - in particular
      in males - must be initiated before puberty if they are to have a positive effect
      on mortality and morbidity during the course of a person's life.

PMID- 14699806
TI  - [Emergencies seminar: acute pulmonary edema].

PMID- 14699807
TI  - [Classification and risk stratification in hypertension Recommendations of the
      European Society for Hypertension (ESH)].

PMID- 14699808
TI  - ["Harmless influenza infection". Suddenly skin and mucosa changes appear].

PMID- 14699809
TI  - [Tinnitus].

PMID- 14699810
TI  - Update-surveillance of health care workers exposed to blood, body fluids and
      bloodborne pathogens in Canadian hospital settings: 1 April, 2000, to 31 March,
      2002.

PMID- 14699812
TI  - Walking away.

PMID- 14699811
TI  - Rebirth of the St. John's Clinic: a successful case study.

PMID- 14699813
TI  - Semen quality in relation to pesticide exposure in Missouri males.

PMID- 14699814
TI  - Initial evaluation and management of the critically burned patient.
AB  - This article is intended to provide treating physicians with a simple evaluation
      and treatment protocol for major burn cases prior to transferring them to a burn
      care facility.

PMID- 14699815
TI  - Saving lives and conserving blood: changing blood transfusion practices at St.
      John's Hospital, Springfield, Missouri.
AB  - We measured mean transfusion rates for 11 conditions accounting for the majority
      of inpatient blood transfusions and the pre-transfusion hemoglobin threshold
      triggering the transfusion. We then developed evidence-based recommendations for
      lower blood hemoglobin transfusion 'triggers.' Implementation of the transfusion
      guidelines and consensus building has decreased blood transfusion for the eleven
      conditions at St. John's Regional Health System (SJRHS) by 11.3% year to date
      (July 2002-March 2003).

PMID- 14699816
TI  - The impact of IMPACT on St. John's Regional Health Center.
AB  - St. John's Regional Health Center (SJRHC) is participating in the Institute for
      Healthcare Improvement's (IHI) IMPACT collaborative, a new IMProvement ACTion
      network of health care organizations that have joined together to improve patient
      care. By utilizing the network for sharing ideas, continuous quality improvement
      tools and support staff and physician involvement, we have achieved three
      important breakthrough improvements in patient flow in the hospital setting. The
      areas highlighted in this article are Perioperative Services, Emergency
      Department Admission, and Transfers to Cardiac Intensive Care Units.

PMID- 14699817
TI  - A comprehensive community breast center--it really can work!
AB  - Can breast care be dramatically improved and positively received? St. John's
      Hospital made the decision to try to develop a comprehensive Breast Cancer Center
      with improved patient care and flow. The goals included more efficiency in
      timeliness, services provided, follow-up, cost, and quality. Additional targets
      were to have happy patients, physicians, and administrators. St. John's Breast
      Center has accomplished all of the goals and more. This article describes how
      this project was accomplished.

PMID- 14699818
TI  - Mapping the primrose patch--a practical approach to herbal therapies in the
      menopause.
AB  - Women suffering post-menopausal symptoms will often seek alternative therapies.
      No alternative therapies have been shown to be more effective for hot flashes
      than estrogen replacement; nonetheless, there are more than 40 products on the
      alternative medicine shelf, which claim to bring relief to women in the
      climacteric. Patients will benefit from physician knowledge of the herbal
      remedies that are now heavily marketed, and apparently widely used, without FDA
      oversight.

PMID- 14699819
TI  - Alcohol and liver disease.

PMID- 14699820
TI  - Carotid dissection presenting as demyelinating disease on magnetic resonance
      imaging.
AB  - Carotid artery dissection carries significant morbidity and mortality if not
      detected early. Carotid artery dissections can produce lesions on Magnetic
      Resonance Imaging (MRI) that may be confused with the characteristic findings in
      Multiple Sclerosis. We present a case of carotid artery dissection presenting
      with signs, symptoms, and MRI findings consistent with Multiple Sclerosis.

PMID- 14699821
TI  - [Treatment with estrogens and Co. in menopause. Farewell to hormone cornucopia].

PMID- 14699823
TI  - [Estrogen plus gestagen especially risky. Breast cancer risk doubled].

PMID- 14699822
TI  - [Indications critically evaluated: hormone-domain hot flashes].

PMID- 14699824
TI  - [Home remedies against common cold. What do the colleagues advise to their
      patients].

PMID- 14699825
TI  - [Post-traumatic stress disorder. What therapy does really help?].

PMID- 14699826
TI  - [First clinical study in Germany. Vaccination against HIV coming soon?].

PMID- 14699827
TI  - [Asthma prevention. Speaking harms the health].

PMID- 14699828
TI  - [Your patient has a sex problem? Talk to him about it].

PMID- 14699829
TI  - [Premature orgasm in the male].
AB  - To date, we have no uniform definition of ejaculatio praecox. In a qualitative
      approach, premature ejaculation is ascribed to a failure to control excitement.
      As causes, organic disorders and erectile dysfunction must be excluded. The
      majority of cases, however, are due to psychological or partnership problems. The
      history-taking should aim, in particular, to uncover possible anxiety in
      conjunction with premature orgasm, and also to establish the reactions of the
      partner. As therapy, medication (local anesthetics, antidepressive agents, PDE-5
      inhibitors) and sexual-therapeutic measures are available. Since few sufferers
      take the initiative in seeking treatment, particular importance attaches to
      providing the public with information about the therapeutic options for treating
      this common disorder.

PMID- 14699830
TI  - [Female sexuality].

PMID- 14699831
TI  - [Pleasure and pain in sexual relations. The basis and reasons for sex counseling
      by the general practitioner].
AB  - An essential factor for successful sex counseling by the family doctor is an
      atmosphere of openness and trust between physician and patient. However, few
      patients will begin to talk about their sexual problems of their own accord. The
      physician should therefore allow himself sufficient time for such counseling, be
      aware of his own limitations, and develop an ear attuned to involuntary remarks
      by the patient. During talks, only sparse use should be made of technical terms,
      the better to encourage the patient. The problems most commonly described in the
      doctor's office are functional disorders with a psychosomatic cause, and
      triggering factors may vary considerably (a high level of stress at the
      workplace, social or financial crises, monotonous leisure activities). In view of
      this, a somatic investigation should always be preceded by careful history
      taking.

PMID- 14699832
TI  - [Sudden anisocoria. An ornamental plant causes irritation].

PMID- 14699833
TI  - [Bronchial asthma -- to set the measuring rod higher. Combination therapy defines
      asthma control anew].

PMID- 14699834
TI  - [Salmeterol + fluticasone in COPD. Complementary treatment principles hold true
      in the COPD management, too].

PMID- 14699835
TI  - [Remedy in age-related vertigo. Seniors with equilibrium].

PMID- 14699836
TI  - [Pouchitis, chronic inflammatory bowel diseases, irritable colon. To prevent with
      a bacteria-cocktail?].

PMID- 14699838
TI  - [Not a subject. Speech and swallowing disorders in dementia].

PMID- 14699839
TI  - [Sudden shadow in the right eye].

PMID- 14699837
TI  - [Secondary prevention after stroke. Doubled performs better].

PMID- 14699840
TI  - [Anorexia nervosa].

PMID- 14699841
TI  - [Structure and functions of cytoplasmic peptide: N-glycanases in eukaryotic
      cells].

PMID- 14699842
TI  - [So-called "green odor" as plant origin--chemistry and biochemistry].

PMID- 14699843
TI  - [Physiological role and mechanism of phagocytic clearance of apoptotic cells].

PMID- 14699844
TI  - [Molecular recognition and cleavage of presequence by mitochondrial processing
      peptidase].

PMID- 14699845
TI  - [Regulatory network of transcription factor MITF in pigment cells].

PMID- 14699846
TI  - [Regulatory mechanism of endocytosis by inositol phospholipids].

PMID- 14699847
TI  - [GA signal transduction via protein degradation].

PMID- 14699848
TI  - [Multiplicity of long-chain acyl-CoA hydrolase and its roles in lipid
      metabolism].

PMID- 14699849
TI  - [Role of SCL/Tall on endothelial and hematopoietic development].

PMID- 14699850
TI  - [Whole genome approach of drug exporter genes and their regulatory networks].

PMID- 14699851
TI  - [Studies on biological activity of antimicrobial peptides, defensins, and the
      inducible mechanism in mammalian cells].

PMID- 14699852
TI  - [Chronic bacterial infections and cancer--from the viewpoint of the epidemiology
      and biological evidences].

PMID- 14699853
TI  - [Life of Shibasaburo Kitasato related to pupils of Ogata Koan].

PMID- 14699854
TI  - [Shibasaburo Kitasato: a pioneer of bacteriology in the world].

PMID- 14699855
TI  - [Great Japanese bacteriologists in the Meiji, Taisho and Showa era].

PMID- 14699856
TI  - [Civilization and infectious diseases--historical review of their relationship].

PMID- 14699857
TI  - [Shifting of emphasis in the world health sector strategy; from political
      concerns to economic ones].
AB  - Primary Health Care, proclaimed by WHO in 1978, is a health strategy that aims to
      achieve the ultimate objective "Health For All", with underlying political
      concerns for ideals such as social justice, equity and human rights. Meanwhile,
      "globalization", urged by the U.S.A., other developed countries and multinational
      corporations, has since promoted liberalization of trade, capital and finance,
      which has in the past few decades been sweeping all over the world. With this
      "new economic liberalism", values that put much emphasis on economic efficiency
      are now at the forefront. The World Bank, which supports the tendency along with
      the International Monetary Fund and the World Trade Organization, has become an
      influential actor in helping developing countries to prosper economically. The
      World Bank, whose basic idea is that investment in health is basic for economic
      growth, has in the 1990s also exerted considerable influence on the international
      health sector with its overwhelming provision of financial assistance. Instead of
      political concerns like equity and human rights, 'economic concerns' such as
      fairer budget allocation, cost-effectiveness, cost reduction and efficiency have
      now become main points for discussion in the international health field. This
      shift in emphasis poses fundamental questions for the core goal of the World
      Health Organization; "Health For All".

PMID- 14699858
TI  - [Body mass index and subsequent risk of hypertension, diabetes and
      hypercholesterolemia in a population-based sample of Japanese].
AB  - OBJECTIVE: To clarify relationships between BMI (body mass index) and the
      incidence of hypertension, diabetes and hypercholesterolemia among a community
      based sample. METHOD: A 4.3-year follow-up study was conducted of 1,427 men and
      women aged 40-69 to examine the relationships between BMI (kg/m2) and the
      incidence of hypertension, diabetes and hypercholesterolemia. RESULTS: During the
      follow-up, there were 118 cases of incident hypertension diagnosed, 56 of
      diabetes and 136 of hypercholesterolemia. After adjusting for sex, age, cognitive
      physical activity, food intake, alcohol intake, smoking, and blood pressure
      level, blood glucose level and serum total cholesterol level at the baseline,
      excess risks with the BMI category of > or = 27.0 versus 21.0-22.9 were found for
      hypertension [relative risk (95% CI) = 1.9(1.0-3.6)] and diabetes [2.9(1.2-7.4)].
      However, no excess risk was evident for the 23.0-24.9 or 25.0-26.9 categories.
      Multivariate relative risks (95%CI) of hypercholesterolemia compared with the BMI
      category of 21.0-22.9 were 1.5 (0.9-2.6) for 23.0-24.9, 1.7(0.9-3.2) for 25.0
      26.9 and 1.6 (0.8-3.1) for > or = 27.0, none of which reached statistical
      significance. When we combined all three diseases, the relative risks (95%CI)
      compared with the BMI category of 21.0-22.9 were 0.9(0.6-1.5) for 23.0-24.9,
      1.2(0.7-2.1) for 25.0-26.9 and 1.8 (1.0-3.3) for > or = 27.0. CONCLUSIONS:
      Increased risks of hypertension, diabetes and lifestyle-related disease were only
      evident with the BMI category > or = 27.0. Education for weight reduction should
      be less emphasized for persons with a BMI of 25.0-26.9 than for these with a
      value of > or = 27.0.

PMID- 14699859
TI  - [Cystic hydatidosis--its occurrence and prevention in Japan].
AB  - The history of cystic hydatidosis (CH) in Japan is reviewed on the basis of case
      reports and other references during the period from 1881 to 2003. A total of 76
      cases were identified as CH patients in Japan of which 47 were reported prior to
      1945 and 29 thereafter. The occurrence was divided into 2 stages before and after
      the Slaughterhouse Act that was brought into force in 1906. The presence of
      endemic foci of CH was suggested before the Act was introduced in Japan,
      especially in southwestern prefectures, and the development of cattle breeding
      and unsanitary small slaughterhouses in the areas were thought to be cause. Japan
      emphasized cattle as a dietary protein source and also for various military
      accouterments such as shoes and rucksacks for soldiers. China was a transit port
      to Japan from Europe and also a big endemic area of CH. Japan had sent a huge
      number of soldiers and citizens to China in the Japanese-Sino and Japanese
      Russian War and a number of cattle, pet dogs and people have also came to Japan
      from China. After enforcement of the Slaughterhouse Act in 1906, the number of CH
      cases decreased dramatically, and only 2 cases were reported for the 30 years
      between 1920 and 1950 in Japan. The situation regarding CH in Japan thus
      suggested the existence of endemic foci in southwestern prefectures, although
      direct evidence was lacking because no one had found E. granulosus in dogs of the
      area. Almost all of the patients recently presenting with CH appear to have been
      infected in overseas endemic countries. The available information strongly
      suggest that sanitary control of slaughterhouses is essential for preventing CH
      in endemic areas. Diagnostic laboratory examinations and appropriate medical
      intervention are clearly important. An animal quarantine system against
      echinococcal infestation of pet dogs should also be established urgently in
      Japan, because hundreds of pet dogs are being imported annually from endemic
      countries in Europe and Asia.

PMID- 14699860
TI  - [Algorithm for application of the "ethical guidelines for epidemiological
      research" and taxonomy of public health research].
AB  - BACKGROUND: "Ethical Guidelines for Epidemiological Research" took effect in July
      2002, with a moral duty of all researchers to comply when conducting
      epidemiological studies although it is not legally binding. Public health
      research entails various forms of studies including not only epidemiological
      studies but also attention to psychological, societal and economic aspects, which
      are outside of the jurisdiction of the guidelines. Hence, confusion may arise
      among members of Japanese Society of Public Health as to whether the study they
      conduct falls within the definition of epidemiological research. The author
      discusses legal interpretations of the guidelines arising in the course of
      translation work as part of government-funded project, "Dissemination of the
      'Ethical Guidelines for Epidemiological Research' via Internet (principal
      investigator: Toru Doi)" and argues that a case-method approach would be best
      suited to enhance understanding by researchers with diverse, non-legal
      backgrounds. METHODS: The author proposes an algorithm for classification of
      studies as to whether the guideline applies, and applies it to all original
      articles published in the Japanese Journal of Public Health (JJPH) in one year
      (March 2002 thru February 2003). The rationale for classification is discussed
      from the strict legal viewpoint in each case. RESULTS: Sixteen out of 46 original
      articles published in JJPH for one year were classified as epidemiological
      studies to which the guidelines apply. Those classified otherwise were
      psychological studies (10), epidemiological studies not targeting specific
      diseases and are exempt form the guidelines (3), purely methodological studies
      (4), economics studies (3), fact-finding or opinion surveys with no hypothesis
      testing (2), as well as studies authorized by law (4) or using unlinkable
      anonymous data only (4), all of which are exempt from the guidelines. Reference
      to ethical considerations in the methodology section as required by the
      instructions for authors was generally well performed in epidemiological studies
      although some shortcomings were noted. DISCUSSIONS: The guidelines affect
      approximately a third of original articles published in the JJPH. The ratio of
      applicable to non-applicable articles was roughly 1 to 2. This gives both authors
      and reviewers confusion as to whether articles are subject to the guidelines and
      would require ethical approval. This case-method approach using actual articles
      readily available to members should help unnecessary confusion and enhance
      appropriate application of the guidelines. (366 words).

PMID- 14699861
TI  - [Radiation therapy in the treatment of lung cancer].
AB  - Although non-small cell lung cancer (NSCLC) has the potential for cure with
      surgical resection, unfortunately less than 15% of all patients and less than 25%
      of those who present with intrathoracic localized disease are candidates for
      curative surgical resection. Elderly patients, even if they have resectable
      disease, often have medical contraindications to surgery, such as cardiovascular
      disease or pulmonary dysfunction. Radiation therapy (RT) for lung cancer has been
      practiced as (1) curative thoracic irradiation for inoperable or unresectable
      NSCLC, (2) preoperative and postoperative irradiation, (3) thoracic irradiation
      for limited-stage small cell lung cancer(SCLC), (4) prophylactic cranial
      irradiation (PCI) for SCLC, and (5) palliative irradiation for more advanced
      disease. Recent evidence indicates that RT with high equivalent doses of 60 Gy or
      more using conventional once daily fractionation may improve the survival rate
      for patients with locally advanced unresectable NSCLC when combined with
      cisplatin-based chemotherapy or administered by altered fractionation. In limited
      stage SCLC, the additions of thoracic RT and prophylactic cranial irradiation to
      systemic chemotherapy have also improved disease control. In patients with more
      advanced disease, RT has provided relief of symptoms. Newer radiotherapeutic
      methods are expected to hold promise in increasing the dose to tumor while
      sparing normal tissue. Recently, heavy ion charged particle therapy,
      brachytherapy, stereotactic irradiation, and multi-daily fractionation have shown
      promise in the treatment of lung cancer. Furthermore, there have been advances in
      the technology for treatment delivery, especially three-dimensional treatment
      planning systems, patient fixation tools, and respiration synchronous systems for
      RT.

PMID- 14699862
TI  - [Dose investigation of superparamagnetic iron oxide (SPIO) SH U 555 A in liver MR
      imaging].
AB  - SH U 555 A, a new superparamagnetic iron oxide (SPIO) contrast agent for liver MR
      imaging, was investigated in terms of safety and efficacy. Eighty-four patients
      with suspected malignant liver tumor were randomly allocated to two groups: the L
      dose group (8 mumol Fe/kg) and H dose group (12 mumol Fe/kg). Efficacy was
      qualitatively evaluated through blinded reading of the MR images. Assessment of
      the images revealed no consistent differences between the L and H dose groups.
      During the 3- to 4-day observation period, a total of 16 adverse events were
      observed in 11 patients: 8 patients in the L dose group and 3 patients in the H
      dose group. Nasal bleeding occurred in 2 of these cases in the H dose group 2 and
      4 days, respectively, after injection. Although patients in the H dose group
      showed a significantly larger transient decrease in Coagulation Factor XI at 4-6
      hr post-injection (p.i.) than patients in the L dose group, analysis of
      covariance revealed an estimated 6.5% difference. There was no prolongation of
      APTT or change in Factor XI at 72-96 hr p.i. Because there were no clinically
      significant differences between the L and H doses, both were considered to be
      safe and effective.

PMID- 14699863
TI  - [Optimal technique of virtual cystoscopy on single-detector helical CT, and
      clinical application].
AB  - The optimal technique of virtual cystoscopy (VC) was determined on single
      detector helical CT using a bladder phantom, and its clinical utility was
      evaluated. A phantom simulating the urinary bladder with 2 dome-shaped polyps
      (diameters 5 and 10 mm) was constructed. Imaging specifications were as follows:
      collimation, 3 and 5 mm; pitch 1; reconstruction interval, 1 and 2 mm. The polyps
      were positioned parallel and perpendicular to the scanning direction. Using these
      data sets, virtual cystoscopic images were generated by a voxel transmission
      technique. The threshold values were changed from -950 HU to -250 HU. Three
      radiologists evaluated visualization of the polyps in terms of proportion and
      shape on different collimations, threshold values, and location, for each size of
      polyp. Results indicated that the optimal technique of VC was as follows:
      collimation 3 mm, pitch 1:1, reconstruction interval 1 mm, and threshold value
      from -550 HU to -500 HU. VC depicted 13 (81.3%) of 16 lesions on the urinary
      bladder and prostate diseases noted on conventional cystoscopy using the optimal
      scanning technique. VC enabled evaluation of the accurate shape of lesions and
      their relation to adjacent mucosa.

PMID- 14699864
TI  - [Infusion MR arteriography during hepatic arterial infusion chemotherapy:
      evaluation of clinical usefulness].
AB  - PURPOSE: We developed a new method of infusion MR arteriography (IMRA) via an
      implantable port system using an infusion pump for the evaluation of drug
      distribution during hepatic arterial infusion chemotherapy. The purposes of this
      study were to optimize the method and evaluate its clinical usefulness. MATERIALS
      AND METHODS: We used 3D-T1 TFE as the most suitable sequence for IMRA according
      to the results of a phantom model experiment. We examined 33 cases of liver
      cancer that had been treated by arterial infusion chemotherapy via the port
      system. The following investigations were performed: degree of tumor enhancement,
      intra- and extrahepatic perfusion abnormality, and related toxicity. The
      evaluation of images was performed separately by two radiologists. RESULTS: IMRA
      provided good images of contrast enhancement, to reveal the perfusion patterns.
      The treatment response rate in the tumor group with well enhancement was higher
      than that of the group with poor enhancement (p < 0.0001). Extrahepatic perfusion
      was well visualized and was correlated with toxicity (p < 0.0001). CONCLUSION:
      IMRA is a useful method to evaluate drug perfusion for the optimization of
      arterial infusion chemotherapy.

PMID- 14699865
TI  - [Creation and evaluation of a concave dose distribution by combining multiple arc
      fields].
AB  - To create a concave dose distribution, a partial shielding radiation technique or
      intensity-modulated radiation therapy (IMRT) is usually required. However, in the
      present study we focused on how to create a concave dose distribution using
      conventional irradiation techniques. A treatment plan was experimentally created
      using planning CT scans of the neck. Two target volumes were predefined: planning
      target volume (PTV) 1, which included macroscopic tumor volume, tonsil, and
      bilateral retropharyngeal node, and PTV2, which included macroscopic and
      microscopic tumor volume. The prescribed doses for PTV1 and PTV2 were 66 Gy and
      50 Gy, respectively. Nine isocenters, 7 in PTV2 and 2 on the sides of PTV2 were
      arranged equally spaced. Seven of the 9 arcs were divided in two arcs in order to
      avoid irradiating the spinal cord and salivary glands. Thus, 9 arcs were used in
      combination with a field size of 4-5 cm x 9-13 fields. Sixteen Gy was given to
      each isocenter with 10 MV photons. The plan was compared with a conventional plan
      (lateral opposing fields with electron boost) by analyzing the dose-volume
      histogram and dose distributions. The horseshoe-like distribution exceeding 66 Gy
      becomes conformal to PTV1, and the V95 of PTV1 (volume receiving 95% of the
      prescribed dose) was compatible with the conventional plan. On the other hand,
      maximum spinal cord dose decreased from 51 Gy with the conventional plan to 40 Gy
      with the 9-arc plan, and parotid gland volume (%) irradiated with > 32 Gy was
      reduced from 99% with the conventional plan to 72% with the 9-arc therapy. Lower
      normal tissue doses to the spinal cord and salivary gland, while maintaining the
      target dose, are achieved using the multiple arc plan, and the technique
      presented may be convenient and useful for facilities that do not yet have full
      access to IMRT.

PMID- 14699866
TI  - [Laryngeal preservation with definitive radiotherapy in radiosensitive
      hypopharyngeal cancer].
AB  - Fifty-seven patients with hypopharyngeal cancer treated by irradiation at Kyushu
      University Hospital between 1985 and 1992 were analyzed retrospectively. They
      included 53 men and 4 women, and their ages ranged from 39 to 83 years (mean, 63
      years). Two patients had stage I, 7 had stage II, 13 had stage III, and 35 had
      stage IV disease according to the UICC (1997) classification. Initially, they
      were irradiated in the conventional way with a dose of 30 Gy, and 17 patients
      with good response were irradiated to curative dose (more than 60 Gy), and 32
      patients with poor response were operated immediately. Medically inoperable or
      unresectable patients were treated in a semiradical way (n = 8). The 5-year
      overall and cause-specific survival rates were 46% and 51%, respectively. Five
      year cause-specific survival rates were 88% for stages I and II (n = 9), 67% for
      stage III(n = 13), and 35% for stage IV (n = 35). Five-year cause-specific
      survival according to treatment method was 58% for surgery and 51% for curative
      radiotherapy. There was no statistically significant difference between the two
      rates. These results suggest that initial radiation response is an important
      factor in deciding on the following treatment method. Curative radiotherapy for
      hypopharyngeal cancer according to initial radiation response is a desirable
      treatment strategy.

PMID- 14699867
TI  - [Comparison of imaging modalities for image-guided radiation therapy (IGRT)].
AB  - The use of a new integrated CT/LINAC combination, in which the CT scanner is
      inside the treatment room, and the same patient couch is used for CT scanning and
      treatment, should allow for accurate and precise correction of interfractional
      set-up errors. Comparison of intentional shifts in phantom position as detected
      by the CT system with shifts detected by an ultrasound localization device
      commonly used for prostate localization, and by an electronic portal imaging
      device, showed the standard deviation of set-up uncertainties to be within 1 mm
      in all directions for each modality. The agreement between the modalities was
      within 2.6 mm, 1.6 mm and 1.7 mm in the superior-inferior (SI), anterior
      posterior (AP) and right-left (RL) directions, respectively. All these modalities
      are, therefore, suitable for image-guided radiation therapy applications. The
      choice of modality can be made based of factors such as anatomical site, inter
      user variations, and patient set-up.

PMID- 14699868
TI  - [Screening chest X-ray examination with kinetic analysis using flat-panel
      detector].
AB  - We are developing dynamic screening radiography to provide kinetic information
      for lung respiratory examination using a flat-panel-detector (FPD) system. We
      modified the FPD system (CANON CXDI-22) to take sequential images for a short
      period of time (10 seconds, 3 frames/sec). Sequential chest radiographs from full
      inspiration to expiration were taken and analyzed for diaphragm movement and
      density changes in local lung areas to objectively detect respiratory anomalies.
      Our methods derived some respiratory functions such as regional air passage and
      lung structure movement, and suggested that the degree of chronic obstructive
      pulmonary disease and interstitial pneumonia could be evaluated quantitatively.

PMID- 14699869
TI  - [Basi-parallel anatomical scanning (BPAS) MRI: a simple MRI technique for
      demonstrating the surface appearance of the intracranial vertebrobasilar artery].
AB  - We modified surface anatomy scanning (SAS) MRI to reveal the surface appearance
      of the vertebrobasilar artery in the cistern. Two-cm-thick heavily T2-weighted
      coronal imaging using the fast spin-echo sequence with gray-scale reversal in
      post-processing was best for our purposes. Basi-parallel anatomical scanning
      (BPAS) MRI could clearly demonstrate fusiform aneurysm and its disappearance at
      the acutely occluded segment of the dissected vertebral artery. This simple MRI
      scanning technique can provide useful information on vertebrobasilar vascular
      lesions especially in patients with arterial dissection.

PMID- 14699870
TI  - [Evaluation of clinical usefulness of Web-based results on distribution of brain
      MRI].
AB  - We evaluated clinical usefulness of MD online Image Match with the clinical
      images of 70 intracranial lesions. Total diagnostic accuracy and image similarity
      between the clinical image and search results was better with enhanced-T1WI. In
      all sequence, localization was matched precisely in more than 90% of cases. MDOL
      Image Match was thought to be useful for enhancing the quality of brain MRI
      diagnosis.

PMID- 14699871
TI  - [Evaluation of ultra-low-dose thoracic multi-detector-row CT using different
      reconstruction kernels and new reconstruction algorithms].
AB  - CT has great advantages in detecting early-stage small lung cancer and is
      becoming common in lung cancer screening. Multi-detector-row CT (MDCT) can
      provide thin-slice images with low radiation exposure. In this study, ultra-low
      dose (5 mAs: 10 mAs, 0.5 sec/rot) thoracic MDCT images were evaluated. We
      describe the differences in image quality and quantity between the different
      reconstruction kernels. We also propose a new reconstruction algorithm (ultra-low
      dose reconstruction algorithm: ULR) for ultra-low-dose thoracic CT, to reduce
      noise and streak artifacts. We are convinced of the usefulness and possibility of
      ultra-low-dose thoracic MDCT with ULR algorithms for lung cancer screening.

PMID- 14699872
TI  - [Secretin-stimulating MRCP: the diagnosis of pancreaticobiliary reflux].
AB  - Pancreaticobiliary malfunction is a clinically important condition that may cause
      the occurrence of biliary malignancies. It is widely accepted that continuous
      reflux of the pancreatic juice into the common bile duct (CBD) and/or gallbladder
      is essential as an etiology of biliary malignancies. It has been also mentioned
      that reflux of the pancreatic juice into the CBD/gallbladder is observed
      regardless of the presence of pancreaticobiliary malfunction. Secretin
      stimulating MRCP may demonstrate not only outflow of the pancreatic juice to the
      duodenum but also the phenomenon of reflux of the pancreatic juice into the
      CBD/gallbladder as enlargement of the CBD/gallbladder. We investigated whether
      secretin-stimulating MRCP can diagnose pancreaticobiliary reflux.

PMID- 14699873
TI  - [Implantation of Palmaz stent for limb stenosis of Y-graft: a case report].
AB  - An 81-year-old woman complained of severe right leg claudication in 2000. She had
      undergone inverted Y-graft placement for infrarenal abdominal aortic aneurysm in
      1998. Magnetic resonance angiography (MRA) revealed severe stenosis at the right
      common iliac graft. Digital subtraction angiography (DSA) demonstrated a rare
      form of stenosis due to organized thrombus. Stent placement was successfully
      performed, utilizing a Palmaz stent. The stent has been patent for three years.
      The patient is asymptomatic and is being followed at our institute.

PMID- 14699874
TI  - What is it about the uterus anyway?
AB  - More fetuses die or are left damaged by preterm delivery than any other cause.
      This is not only a devastating problem for the family, but a very expensive
      problem as well. The drugs physicians currently have available to treat women in
      labor are largely ineffective and in some cases, given their toxicity, may
      violate the sacred goal of treatment, "Primum Non Nocere". At the present time,
      we do not understand the regulation of the uterine smooth muscle that leads to
      birth. If we knew more, particularly how best to induce relaxation of a uterus
      undergoing preterm labor, we could revolutionize the treatment of this problem
      and potentially save thousands of lives and reduce morbidity greatly. The ability
      of nitric oxide to relax smooth muscle has led to an interest in employing nitric
      oxide-donors in the treatment of preterm labor. However, fundamental differences
      exist in the regulation of uterine and other smooth muscles. While some are
      treating preterm labor using nitric oxide, this approach exposes mother and fetus
      to unwanted effects of nitrovasodilators. With more detailed knowledge of uterine
      smooth muscle signaling, an opportunity exists to develop new therapeutics. We
      discuss the current treatment for preterm labor and consider the evidence that
      nitric oxide-mediated relaxation of myometrial smooth muscle is cyclic nucleotide
      independent. Knowledge of the regulation of myometrium that is disparate from
      that of other smooth muscles may reveal molecular targets that are unique to the
      myometrium and can there for be pursued as tocolytic targets.

PMID- 14699875
TI  - Fetal origins of adult disease.

PMID- 14699876
TI  - Brain angiotensinergic activity: the state of our current knowledge.

PMID- 14699877
TI  - The cardiovascular system in microgravity: symposium summary.

PMID- 14699878
TI  - Cygnets: spatial and temporal analysis of intracellular cGMP.

PMID- 14699879
TI  - Dynamic regulation of cAMP signaling by cGMP in the cardiovascular system: roles
      of phosphodiesterase 2 and phosphodiesterase 3 enzymes.

PMID- 14699880
TI  - Vascular actions of the polyphenolic catechin gallate EGCG: endothelium-dependent
      contraction and relaxation.

PMID- 14699881
TI  - Aminopeptidase A, generating one of the main effector peptides of the brain renin
      angiotensin system, angiotensin III, plays a key role in central control of blood
      pressure.

PMID- 14699882
TI  - Increase of human plasma antioxidant capacity with a novel formulation of
      antioxidants.

PMID- 14699883
TI  - Effect of valproic acid on levels of GABA and glutamic acid in pentylenetetrazole
      damaged rat brain.

PMID- 14699884
TI  - Changes in the ionotropic glutamate receptors in the mouse cerebral cortex during
      development and aging.

PMID- 14699885
TI  - Opposite gender-specific increases in peripheral benzodiazepine receptor (PBR)
      expression in rat brain after single administration of the GABA antagonists
      heptachlor and heptachlor epoxide.

PMID- 14699886
TI  - Time course of COX and eNOS renal expression during rat pregnancy.

PMID- 14699887
TI  - Phospholipase C inhibitor U73122 attenuates the dipsogenic response induced by
      angiotensin II.

PMID- 14699888
TI  - 125I-angiotensin I binding in the rat forebrain.

PMID- 14699889
TI  - Comparative effect of chronic administration of two 17 beta-aminoestrogens,
      butolame and pentolame, on the reproductive system, fertility and progeny outcome
      of the male rat.

PMID- 14699890
TI  - Effect of chronic administration of two aminoestrogens (butolame and pentolame)
      on epididymal protein patterns of the rat.

PMID- 14699891
TI  - Changes in small conductance potassium channel expression in human myometrium
      during pregnancy measured by RT-PCR.

PMID- 14699892
TI  - Differential antinociceptive effects of L-arginine and 3-morpholinosydoimine.

PMID- 14699893
TI  - Correlation of inbred mouse responsiveness to nitrous oxide (N2O) with brain
      nitric oxide synthase (NOS) activity.

PMID- 14699894
TI  - Comparative bioavailability of two oral formulations manufactured in Mexico
      containing glyburide and metformin in diabetic patients.

PMID- 14699895
TI  - Possible antitumoral effect of the crude venom of Cassiopea xamachana (Cnidaria:
      Scyphozoa) on tumors of the central nervous system induced by N-ethyl-N
      nitrosourea (ENU) in rats.

PMID- 14699896
TI  - Combination of diclofenac plus B vitamins in acute pain after tonsillectomy: a
      pilot study.

PMID- 14699897
TI  - Synergistic interaction between spinal gabapentin and oral B vitamins in a
      neuropathic pain model.

PMID- 14699898
TI  - Analysis of the criteria used to assign grades in two Mexican medical schools as
      indicators of quality in the assessment of student learning.

PMID- 14699899
TI  - A Web-based virtual dog lab aimed at teaching ideas, not techniques.

PMID- 14699900
TI  - Can adrenal insufficiency be diagnosed on clinical and laboratory data basis in
      patients with AIDS?

PMID- 14699901
TI  - Pharmacokinetics of stavudine by oral administration to healthy Mexican
      volunteers.

PMID- 14699902
TI  - Effects of local infusion of methylmercury on the rat brain: GFAP
      immunohistochemistry and water maze learning.

PMID- 14699903
TI  - The role of nitric oxide in locomotor regulation in mice and its interaction with
      nitrous oxide.

PMID- 14699904
TI  - The role of the dorsal raphe in the sleep disruptions produced by ozone exposure.

PMID- 14699905
TI  - In vitro antibacterial activity of Germisol on bacterial strains isolated from
      dental patients.

PMID- 14699906
TI  - Clinical manifestations of hyperthyroidism after treatment with selective beta 1
      adrenoceptor blocking agents.

PMID- 14699907
TI  - The effect of propranolol, atenolol and metoprolol on the serum levels of
      thyroxin (T4) and triiodothyronine (T3).

PMID- 14699908
TI  - Enzymatic and binding activities of 5 alpha-reductase and androgen receptors in
      hamster prostate.

PMID- 14699909
TI  - Additive effect of midazolam and progesterone on the EEG in rats.

PMID- 14699910
TI  - Comparative bioavailability of two oral formulations of ciprofloxacin.

PMID- 14699911
TI  - Synthesis and hepatoprotective activity of 3,4 diacetyl; 3,4 dibenzyl caffeic and
      4-(dimethylamino) cinnamic acids.

PMID- 14699912
TI  - Hypoglycemic activity of two polysaccharides isolated from Opuntia ficus-indica
      and O. streptacantha.

PMID- 14699914
TI  - Study of the anti-hyperglycemic effect of anti-diabetic plants in rabbits with
      impaired glucose tolerance.

PMID- 14699913
TI  - Crossover and double blind study with metformin and rosiglitazone in impaired
      glucose tolerance subjects.

PMID- 14699915
TI  - Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate.

PMID- 14699916
TI  - Investigation of the effects of a sapogenin-rich preparation from a Jamaican yam
      (Dioscorea sp.) on blood cholesterol levels in rats.

PMID- 14699917
TI  - Effect of hepatic encephalopathy on ligand binding to metabotropic glutamate
      receptors in brain synaptic membranes.

PMID- 14699918
TI  - Evaluation of morphine analgesic activity in rats submitted to repetitive intra
      articular injections of uric acid.

PMID- 14699919
TI  - Participation of the NO-cyclic GMP pathway in rofecoxib-induced antinociception.

PMID- 14699920
TI  - Pharmacokinetics of the commonly used NSAID: nimesulide by oral administration to
      healthy Mexican volunteers.

PMID- 14699921
TI  - Failure of standardized psychophysical tests for DWI to distinguish between blood
      alcohol levels of 0.000 and 0.080 to 0.125 g/dl.

PMID- 14699922
TI  - The HIPAA transactions standards deadline: reprieve, no reprieve or state of
      confusion?

PMID- 14699923
TI  - Managing change within the healthcare environment.
AB  - In the healthcare environment, there are many catalysts for change, including
      federal and state regulations, increased utilization, patients' expectations,
      competition, declining reimbursement and the technologist shortage. Regardless of
      what organization you work in, change creates pressure internally. This is
      especially true of organizations that have not had to deal with much change. The
      three most common responses are: 1) senior managers tend to isolate themselves
      from the effects of change on staff members; 2) middle managers tend to feel
      squeezed between the need to implement change and the need to support staff
      members; and 3) employees tend to feel attacked and betrayed by change. The
      following five steps will help you work with your staff as you introduce and
      implement change: prepare your employees, plan thoroughly, develop a transitional
      line of authority, stay flexible during implementation, and encourage self
      management, acknowledging those who helped make the change work. When change is
      implemented, it is important to understand that people will move through four
      stages of reaction: denial, resistance, exploration and commitment. As a general
      rule, individuals will go through all four stages, but the speed at which they
      move through them will be different. Managers need to assist employees who get
      stuck in certain stages. To implement change as successfully as possible, follow
      these four steps: communicate about change, deal with resistance, increase team
      involvement, and use visionary leadership.

PMID- 14699924
TI  - Storage options for the healthcare enterprise.
AB  - The storage objectives for the healthcare enterprise (HE) are to ensure that
      information (images and data) are readily available anywhere and at anytime,
      images and data are secure, and the storage fulfills legal requirements and the
      Health Insurance Portability and Accountability Act (HIPAA). These objectives
      must be satisfied at a minimum economic cost with respect to personnel, hardware,
      software, space and telecommunications. Many approaches and storage
      configurations meet these objectives. Which approach is chosen will depend on the
      size of the institution, patient population, geographic distribution of the
      institutions (if more than one), type of facility (such as a hospital, outpatient
      clinic or private imaging center), and financial investment objectives. The
      quantity of storage required depends on the characteristics of the modalities,
      the number of imaging devices and databases, the number and location of imaging
      sites that make up the HE, the size of the data and image, and the projected
      procedure volume growth. The only certainty with respect to storage requirements
      is that they will increase significantly with time. The types of storage required
      in the HE can be described by their functions: Active storage includes both
      online and long-term storage. Backup images are temporarily backed up on the
      limited storage capacity of the modality for several days or longer. Additional
      copies of the study are made on different media (e.g., disk, DVD or tape), in
      different locations. The process of backing up data and images must be automated.
      Effective April 21, 2005, HIPAA requires that all healthcare entities have a
      disaster recovery plan in effect. This requires that a copy of all medical data
      be secure, retrievable and maintained in a second location, such that if the
      primary copy of the data is destroyed or made unavailable, the disaster recovery
      copy would be available. Planning for the HE archive is critical if the HE is to
      work productively in an integrated digital environment. The information
      technology department must be an integral part of planning for the HE archive,
      which must be located in a secure data center and not under the management of any
      single clinical department. After the technologies currently available are
      evaluated, it is imperative that the chosen solution is cost-effective and
      scalable, and that it will allow the HE to take advantage of future storage and
      storage management technology.

PMID- 14699925
TI  - Transforming the patient experience in radiation therapy.
AB  - Healthcare providers are paying more attention to behavioral neuroscience
      research that confirms what patients intuitively know: physical environments
      deeply influence one's sense of well being. Recognizing the importance of
      comforting environments, healthcare providers have been working with architects
      to design new facilities around the patient's experience. This doesn't mean that
      functional and technical considerations are unimportant; it's just that the
      patient's experience comes first. The patient is the most important user of a
      healthcare facility, and yet is the only user not sitting at the table during
      design meetings. For this reason, some healthcare providers work with their
      architects to develop the conceptual design from the patient's standpoint before
      seeking detailed staff input. Many indignities experienced by patients may be
      unwittingly imposed by caring and dedicated professional staff. Medical clutter,
      waste containers, water coolers, coffee makers, personal displays and decorations
      add up to create a distressing level of visual chaos. Departments are required to
      eliminate clutter and maintain a calm, pleasing environment. Employees appreciate
      a well-designed physical environment, too. Facilities that reduce stress for
      patients have the same impact on staff, alleviating tension as they care for
      patients. Putting the patient's experience first need not add capital
      construction cost to a project. Rearranging spaces for the sake of the patient
      adds no more to floor area. Added windows, skylights and interior finishes can
      add cost, but the incremental cost of these amenities is small in proportion to
      the total project cost. Facilities project powerful visual dues about an
      institution's values. Providers who carefully plan for a positive patient
      experience traditionally enjoy strong reputations and exceptional customer
      loyalty. These providers know that good design is not simply wrapping a pretty
      facade around a building or decorating the lobby. Good design is the careful
      orchestration of uplifting and encouraging experiences for patients throughout
      their entire visit. For providers who achieve this, architecture becomes evidence
      that they put their patients first.

PMID- 14699926
TI  - A comparison of film-screen, CR and DR: a community hospital time-motion study.
AB  - The purpose of this study was to compare technologist efficiency for conventional
      radiography, computed radiography (CR) and direct radiography (DR) for two types
      of general x-ray examinations. The study was performed at St. Joseph's Health
      Centre, in Toronto, Canada. The study spanned eight calendar months. Two views of
      the chest and three views of the ankle were chosen as representative examinations
      for analysis. Patient examination times were recorded on the radiology
      information system for both types of studies for conventional radiography, CR and
      DR. There was a significant difference in average time of examination for all
      three types of imaging formats for chest studies and between conventional
      radiography and CR or DR for ankle radiographs. There was no significant
      difference between examination times for ankle studies when CR and DR were
      compared. The median time of examination of the chest was 18 minutes, eight
      minutes and six minutes for conventional radiography, CR and DR respectively. The
      median time of examination for ankle radiographs were 22 minutes, seven minutes
      and five minutes for conventional radiography, CR and DR respectively.
      Technologists efficiency is significantly improved with the implementation of a
      DR system and CR system when compared to conventional radiography. DR may not
      deliver significant improvements in efficiencies for certain types of
      examinations.

PMID- 14699927
TI  - Volumetric CT: creating a new paradigm for image acquisition and review.
AB  - With the advent of fast, thin-slice CT, volumetric imaging is a practical and
      dose-efficient reality. However, the acquisition of many image slices at 0.5 mm
      thickness requires a new paradigm in image review. This article describes a
      hierarchical approach to handling the vast data set. The use of volume rendering
      and multiplanar reformatting techniques are critical in the process.
      Implementation of this approach at Long Beach Memorial Medical Center has
      resulted in greater clinical use of CT and improved diagnostic accuracy, while
      maintaining an acceptable throughput.

PMID- 14699928
TI  - Patience with patients.

PMID- 14699929
TI  - Simulating reality with Immersion Medical. Interview by Semahat S. Demir.

PMID- 14699930
TI  - Estimating cost in health economic analyses.

PMID- 14699931
TI  - Repair and restore with tissue engineering.

PMID- 14699932
TI  - Novel polyphosphazene-hydroxyapatite composites as biomaterials.

PMID- 14699933
TI  - Osteoblast and chondrocyte interactions during coculture on scaffolds.

PMID- 14699934
TI  - Association polymers for modulated release of bioactive proteins.

PMID- 14699936
TI  - Tissue engineering with mesenchymal stem cells.

PMID- 14699935
TI  - Scaffold-based articular cartilage repair.

PMID- 14699937
TI  - Genetically modified mesodermal-derived cells for bone tissue engineering.

PMID- 14699938
TI  - Addressing cell-sourcing limitations with gene therapy.

PMID- 14699939
TI  - An extracellular matrix extract for tissue-engineered cartilage.

PMID- 14699940
TI  - Analyzing bone, blood vessels, and biomaterials with microcomputed tomography.

PMID- 14699941
TI  - Minimally invasive tissue engineering composites and cell printing.

PMID- 14699942
TI  - PC-based gamma knife radiosurgery dose calculation.

PMID- 14699943
TI  - Cardiac cell networks on elastic microgrooved scaffolds.

PMID- 14699944
TI  - Quantification of S. aureus binding to extracellular matrix molecules using
      optical tweezers.

PMID- 14699945
TI  - Nanoengineered polyelectrolyte micro- and nano-capsules as fluorescent potassium
      ion sensors.

PMID- 14699946
TI  - Quantitative measurements of active and passive mechanical properties of adult
      cardiac myocytes.

PMID- 14699947
TI  - Astray amongst multiple universes.

PMID- 14699948
TI  - Marketing a medical device without a 510(k).

PMID- 14699949
TI  - [Influence of the buffer capacity of amine fluoride-containing toothpastes and
      gels in enamel erosion].
AB  - The aim of the study was to evaluate the abrasion resistance of eroded enamel
      brushed with experimental toothpastes and fluoride gels of varying buffering
      capacities. 50 Specimens were prepared from extracted human molars and cycled
      through three alternating de- and remineralizations including brushing abrasion
      in a brushing machine. Demineralization was accomplished by immersing the samples
      in 1% citric acid (5 min), remineralization occurred during immersing the samples
      in artificial saliva (1 min). Groups of ten samples were brushed with either one
      of the toothpaste (A-C) or one of the fluoridated gels (D-E). Toothpastes and
      gels were produced on the basis of elmex toothpaste or elmex-gelee (GABA
      International AG, Switzerland). Amount of titrable acid was defined as amount
      (mg) of 1 N KOH needed for neutralization of 1 g toothpaste or gel (A: 6 mg, B:
      12 mg, C: 24 mg, D: 3.1 mg, E: 10 mg KOH). The following abrasion values (mean +
      S.D. [micron]) were obtained profilometrically: A: 6.76 +/- 2.05, B: 6.84 +/-
      1.19, C: 8.28 +/- 2.89, D: 4.19 +/- 1.09 and E: 0.83 +/- 0.61. No significant
      difference in abrasion between the toothpastes was found. The fluoride gel with
      the higher buffering capacity (E) exhibited significantly less abrasion than the
      gel with the lower buffering capacity (D). It is concluded that in eroded enamel
      buffering capacity of the tested fluoridated toothpastes has no effect on
      abrasion, whereas use of fluoride gel with a higher buffering capacity leads to
      reduced abrasion values.

PMID- 14699950
TI  - [Characterization of three light sources. Study of their efficiency].
AB  - Light-emitting sources are currently used to activate the setting reaction of
      restorative composite resins. It is well known that the polymerization extent of
      the resins will highly influence their clinical behavior. The monomer-polymer
      transformation will mostly depend on the chemical nature of the photo-initiators
      used and on the luminous energy given by the curing device. The aims of this
      study were to characterize three light curing devices and to compare their
      efficiency to polymerize a composite resin (SureFil). For that purpose, the
      emission spectra and the irradiance of a plasma arc (Flipo), a QTH visible light
      (Elipar Trilight), and a LEDs curing device (Elipar Freelight) were measured.
      Then, the depth of cure and the Vickers hardness of composite samples were
      evaluated, for each curing device, as a function of the exposure time. The
      emission spectra obtained showed the irradiance of the visible light emitted as a
      function of the wavelength, which was different for each light-curing device. The
      maximum cured depth (approximately 4 mm) give only a qualitative indication of
      the extent of the polymerization, as the hardness of the composite samples
      diminished as a function of the depth. Moreover, it strongly depended on the
      exposure time. Hence, to obtain a hardness of approximately 100 HV 0.5 at 2 mm
      depth, the illumination time must be at least of 3 s with the plasma arc Flipo,
      10 s with the LEDs Elipar Freelight and 20 s with the QTH Elipar Trilight. In
      order to efficiently polymerize a composite resin, the emission spectra of the
      luminous source shall correspond with the absorption spectra of the photo
      initiators. The present study showed that the LEDs Elipar Freelight is the most
      efficient curing device when the camphorquinone is used, as 92% of the emitted
      energy will be absorbed by the initiator. However, the power of this source is
      relatively low, hence higher exposure time shall be used.

PMID- 14699951
TI  - [Tooth transplantation].
AB  - Tooth transplantations provide the option of replacing lost or missing teeth in a
      biological fashion. On account of their high success rates and primarily in
      Scandinavian countries, they are a popular alternative to orthodontic or
      prosthetic treatment--particularly in case of children or young people losing
      teeth in accidents. Success of the treatment is ensured by corresponding
      diagnosis and good preoperative planning. Tissue-conserving transplant collection
      and the corresponding conditioning of the transplant bed are of decisive
      importance for the regeneration of the pulp and the periodontium. The success of
      the therapy is also influenced by the type and duration of splinting. Depending
      on the surgical technique and the transplanted tooth, the success rates are
      between 78% and 96%. The success criteria of a transplantation are defined
      clinically and radiologically. The diagnosis for transplantation is made from an
      orthodontic, endodontic, traumatologic, periodontologic and cardiologic
      perspective. The present article provides an overview of literature and shows
      current plantation techniques.

PMID- 14699952
TI  - [Outcome of 500 cases of transcortical anesthesia carried out as the first
      choice].
AB  - Transcortical anesthesia, like all anesthetic techniques, is founded on
      anatomical, physiological and histological principles. Its fundamental principle
      and clinical data that support it indicate that it could advantageously replace
      most other techniques. Indeed, a study carried out by 3 dental surgeons involving
      500 transcortical procedures as the first choice for anesthesia confirms this
      possibility and emphasizes the principal advantages: Immediate anesthesia of
      several (2 to 6) maxillary or mandibular teeth with a single vestibular injection
      (without additional palatine or lingual injection); elimination of cheek and lip
      numbness; use of concentrated vasoconstrictor with no risk of necrosis to solve
      the problem of immediate anesthesia of teeth with pulpitis.

PMID- 14699953
TI  - Trafficking the NGF signal: implications for normal and degenerating neurons.
AB  - Nerve growth factor (NGF) activates TrkA to trigger signaling events that promote
      the survival, differentiation and maintenance of neurons. The mechanism(s) that
      controls the retrograde transport of the NGF signal from axon terminals to neuron
      cell bodies is not known. The 'signaling endosome' hypothesis stipulates that
      NGF, TrkA and signaling proteins are retrogradely transported on endocytic
      vesicles. Here, we provide evidence for the existence of signaling endosomes.
      Following NGF treatment, clathrin-coated vesicles (CCVs) contain NGF bound to
      TrkA together with activated signaling proteins of the Ras/pErk1/2 pathway. NGF
      signals from isolated CCVs through the Erk1/2 pathway. Early endosomes appear to
      represent a second type of signaling endosomes. We found that NGF induced a
      sustained activation of Rap1, a small monomeric GTP-binding protein of the Ras
      family, and that this activation occurred in early endosomes that contain key
      elements of Rap1/pErk1/2 pathway. We discuss the possibility that the failure of
      retrograde NGF signaling in a mouse model of Down syndrome (Ts65Dn) may be due to
      the failure to retrograde transport signaling endosomes. It is important to
      define further the significance of signaling endosomes in the biology of both
      normal and degenerating neurons.

PMID- 14699954
TI  - The p75 neurotrophin receptor: multiple interactors and numerous functions.
AB  - The neurotrophin receptor p75 (p75NTR), is involved in a diverse array of
      cellular responses, including apoptosis, neurite outgrowth and myelination.
      Stimulation of p75NTR with neurotrophin can activate multiple downstream signals,
      including the small GTP binding protein Rac, the transcription factor NF-kappa B
      and the stress activated kinase, JNK. How these signals are generated and
      regulated to produce a specific cellular effect has yet to be fully elucidated. A
      number of proteins have recently been shown to interact with the intracellular
      domain of p75NTR. Here, we review these p75NTR interacting factors and the
      current evidence as to how they contribute to the functional effects of p75NTR
      activation.

PMID- 14699955
TI  - The role of neurotransmission and the Chopper domain in p75 neurotrophin receptor
      death signaling.
AB  - The role of p75 neurotrophin receptor (p75NTR) in mediating cell death is now
      well characterized, however, it is only recently that details of the death
      signaling pathway have become clearer. This review focuses on the importance of
      the juxtamembrane Chopper domain region of p75NTR in this process. Evidence
      supporting the involvement of K+ efflux, the apoptosome (caspase-9, apoptosis
      activating factor-1, APAF-1, and Bcl-xL), caspase-3, c-jun kinase, and p53 in the
      p75NTR cell death pathway is discussed and regulatory roles for the p75NTR
      ectodomain and death domain are proposed. The role of synaptic activity is also
      discussed, in particular the importance of neutrotransmitter-activated K+
      channels acting as the gatekeepers of cell survival decisions during development
      and in neurodegenerative conditions.

PMID- 14699956
TI  - The role of NT-3 signaling in Merkel cell development.
AB  - Merkel cells originate from the neural crest. They are located in hairy and
      glabrous skin and have neuroendocrine characteristics. Together with A beta
      afferents, Merkel cells form a slowly adapting mechanoreceptor, the Merkel nerve
      ending, which transduces steady skin indentation. Neurotphin-3 (NT-3) plays
      important roles in neural crest cell development. We thus sought to determine
      whether neurotrophin signaling is essential for Merkel cell development in the
      whisker pad of the mouse. Our data indicate that at embryonic day 16.5 (E 16.5),
      NT-3 and its receptors, p75 neurotrophin receptor (p75NTR) and tyrosine kinase
      receptor, TrkC are not expressed at detectable levels in Merkel cells. After a
      perinatal switch, however, Merkel cells in whiskers of newborn mice are
      immunoreactive for p75NTR, TrkC and NT-3. Immunoreactivity of all three markers
      persists into adulthood. By contrast, innervating fibers are intensely p75NTR
      immunoreactive in E16.5 whiskers, but no TrkC immunoreactivity is detected. At
      birth, and at 6 weeks of age, afferent fibers are intensely immunoreactive for
      both p75NTR and TrkC. In TrkC null whiskers, numerous Merkel cells are present at
      E16.5, and they are innervated. We draw three major conclusions from these
      observations: (i) NT-3 signaling through p75NTR or TrkC is not required for the
      development and prenatal survival of either a major subset or of all Merkel
      cells, (ii) the postnatal survival of Merkel cells is supported by autocrine or
      paracrine NT-3, rather than by neuron-derived NT-3, and (iii) Merkel cell-derived
      NT-3 is not a chemoattractant for innervating A beta fibers, but is likely to be
      involved in maintaining Merkel cell innervation postnatally.

PMID- 14699957
TI  - Stem cells and nervous tissue repair: from in vitro to in vivo.
AB  - Recent development in stem cell biology has indicated a new possible approach for
      the treatment of neurological diseases. However, in spite of tremendous hope
      generated, we are still on the way to understand if the use of stem cells to
      repair mature brain and spinal cord is a reliable possibility. In particular, we
      know very little on the in situ regulation of adult neural stem, and this also
      negatively impact on cell transplant possibilities. In this chapter we will
      discuss issues concerning the role and function of stem cells in neurological
      diseases, with regard to the impact of features of degenerating neurons and glial
      cells on in situ stem cells. Stem cell location and biology in the adult brain,
      brain host reaction to transplantation, neural stem cell reaction to experimental
      injuries and possibilities for exogenous regulation are the main topics
      discussed.

PMID- 14699958
TI  - Pathways of survival induced by NGF and extracellular ATP after growth factor
      deprivation.
AB  - In a previous work we demonstrated that extracellular adenosine-5'-triphosphate
      (ATP), acting on P2 receptors, exerts neuritogenic and trophic effects on the
      phaeochromocytoma PC12 cell line. These actions are comparable to those sustained
      by nerve growth factor (NGF) and involve several overlapping pathways. In this
      work, we describe some of the mechanisms recruited by ATP and NGF in maintaining
      PC12 cell survival after serum deprivation. We show that both ATP and NGF
      upregulate the expression of the stress-induced heat shock protein HSP70 and
      HSP90, whilst glucose-response protein GRP75 and GRP78 are not affected. In
      parallel with NGF, ATP prevents the cleavage and activation of caspase-2 and
      inhibits the release of cytochrome c from mitochondria into the cytoplasm.
      Finally, neither NGF, nor ATP directly modulate the expression of P2 receptors in
      the induction of cell survival. Our data contribute to dissect the biological
      mechanisms activated by extracellular purines exerting trophic actions and to
      establish that survival and neurite outgrowth lie on different mechanistic
      pathways.

PMID- 14699959
TI  - ProNGF: a neurotrophic or an apoptotic molecule?
AB  - Nerve growth factor (NGF) acts on various classes of central and peripheral
      neurons to promote cell survival, stimulate neurite outgrowth and modulate
      differentiation. NGF is synthesized as a precursor, proNGF, which undergoes
      processing to generate mature NGF. It has been assumed, based on studies in the
      mouse submandibular gland, that NGF in vivo is largely mature NGF, and that
      mature NGF accounts for the molecule's biological activity. However, recently we
      have shown that proNGF is abundant in central nervous system tissues whereas
      mature NGF is undetectable, suggesting that proNGF may have a function distinct
      from its role as a precursor. A recent report that proNGF has apoptotic activity
      contrasts with other data demonstrating that proNGF has neurotrophic activity.
      This chapter will review the structure and processing of NGF and what is known
      about the biological activity of proNGF. Possible reasons for the discrepancies
      in recent reports are discussed.

PMID- 14699961
TI  - Neural stem and progenitor cells: choosing the right Shc.
AB  - Neural stem cell (NSCs) are self-renewing, multipotent cells able to generate
      neurons, astrocytes and oligodendrocytes. Since their identification, these
      properties have made NSCs an attractive subject for therapeutic applications to
      the damaged brain. In this context, understanding the mechanisms and the
      molecules regulating their biological properties is important and it is focused
      to gain control over their proliferative and differentiative potential. Here we
      will discuss values and unsolved aspects of the system and the employment of
      potentially key molecular targets for proper control of NSCs fate.

PMID- 14699960
TI  - NGF deprivation-induced gene expression: after ten years, where do we stand?
AB  - Nerve growth factor (NGF) is required for the survival of developing sympathetic
      and sensory neurons. In the absence of NGF, these neurons undergo protein
      synthesis-dependent apoptosis. Ten years have gone by since the first reports of
      specific genes being upregulated during NGF deprivation-induced cell death. Over
      the last decade, a few additional genes (DP5, Bim, SM-20) have been added to a
      list that began with cyclin D1 and c-jun. In this chapter, we discuss the
      evidence that these genes act as regulators of neuronal cell death. We also
      suggest a hypothesis for how one gene, SM-20, may function to suppress a self
      protection mechanism in NGF-deprived neurons.

PMID- 14699962
TI  - Acute and long-term synaptic modulation by neurotrophins.
AB  - While it has now been well accepted that neurotrophins play an important role in
      synapse development and plasticity, the specific effects of each neurotrophin on
      different populations of neurons at different developmental stages have just
      begun to be worked out. Moreover, the cellular and molecular mechanisms
      underlying the synaptic function of neurotrophins remain poorly understood. In
      general, synaptic effects of neurotrophins could be divided into two categories:
      acute effect on synaptic transmission and plasticity occurring within seconds or
      minutes after cells are exposed to a neurotrophin, and long-term effect on
      synaptic structures and function that takes days to accomplish. In this review I
      have considered the previous findings on neurotrophic regulation of synapses in
      view of these two categories. Acute and long-term effects of neurotrophins are
      reexamined in detail in three model systems: the neuromuscular junction, the
      hippocampus and the visual cortex. Potential molecular mechanisms that mediate
      the acute or long-term neurotrophic regulation are discussed. Efforts are made to
      understand the mechanistic differences between the two effects and their
      relationships. Further study of these mechanisms will help us better understand
      how neurotrophins can achieve diverse and synapse-specific modulation.

PMID- 14699963
TI  - Neurotrophic factors and CNS disorders: findings in rodent models of depression
      and schizophrenia.
AB  - Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are
      proteins involved in neuronal survival and plasticity of dopaminergic,
      cholinergic and serotonergic neurons in the central nervous system (CNS). Loss of
      neurons in specific brain regions has been found in depression and schizophrenia,
      and this chapter summarizes the findings of altered neurotrophins in animal
      models of those two disorders under baseline condition and following
      antidepressive and antipsychotic treatments. In a model of depression (Flinders
      sensitive line/Flinders resistant line; FSL/FRL rats), increased NGF and BDNF
      concentrations were found in frontal cortex of female, and in occipital cortex of
      male 'depressed' FSL compared to FRL control rats. Using the same model, the
      effects of electroconvulsive stimuli (ECS) and chronic lithium treatment on brain
      NGF, BDNF and glial cell line-derived neurotrophic factors were investigated. ECS
      and lithium altered the brain concentrations of neurotrophic factors in the
      hippocampus, frontal cortex, occipital cortex and striatum. ECS mimic the effects
      of electroconvulsive therapy (ECT) that is an effective treatment for depression
      and also schizophrenia. Since NGF and BDNF may also be changed in the CNS of
      animal models of schizophrenia, we investigated whether treatment with
      antipsychotic drugs (haloperidol, risperidone, and olanzapine) affects the
      constitutive levels of NGF and BDNF in the CNS. Both typical and atypical
      antipsychotic drugs altered the regional brain levels of NGF and BDNF. Other
      studies also demonstrated that these drugs differentially altered neurotrophin
      mRNAs. Overall, these studies indicate that alteration of brain level of NGF and
      BDNF could constitute part of the biochemical alterations induced by
      antipsychotic drugs.

PMID- 14699964
TI  - Discovering novel phenotype-selective neurotrophic factors to treat
      neurodegenerative diseases.
AB  - Astrocytes and neurons in the central nervous system (CNS) interact functionally
      to mediate processes as diverse as neuroprotection, neurogenesis and
      synaptogenesis. Moreover, the interaction can be homotypic, implying that
      astrocyte-derived secreted molecules affect their adjacent neurons optimally vs
      remote neurons. Astrocytes produce neurotrophic and extracellular matrix
      molecules that affect neuronal growth, development and survival, synaptic
      development, stabilization and functioning, and neurogenesis. This new knowledge
      offers the opportunity of developing astrocyte-derived, secreted proteins as a
      new class of therapeutics specifically to treat diseases of the CNS. However,
      primary astrocytes proliferate slowly in vitro, and when induced to immortalize
      by genetic manipulation, tend to lose their phenotype. These problems have
      limited the development of astrocytes as sources of potential drug candidates. We
      have successfully developed a method to induce spontaneous immortalization of
      astrocytes. Gene expression analysis, karyotyping and activity profiling data
      show that these spontaneously immortalized type-1 astrocyte cell lines retain the
      properties of their primary parents. The method is generic, such that cell lines
      can be prepared from any region of the CNS. To date, a library of 70 cell lines
      from four regions of the CNS: ventral mesencephalon, striatum, cerebral cortex
      and hippocampus, has been created. A phenotype-selective neurotrophic factor for
      dopaminergic neurons has been discovered from one of the cell lines (VMCL1). This
      mesencephalic astrocyte-derived neurotrophic factor (MANF) is a 20 kD,
      glycosylated, human secreted protein. Homologs of this protein have been
      identified in 16 other species including C. elegans. These new developments offer
      the opportunity of creating a library of astrocyte-derived molecules, and
      developing the ones with the best therapeutic indices for clinical use.

PMID- 14699965
TI  - Neurobehavioral coping to altered gravity: endogenous responses of neurotrophins.
AB  - An altered gravitational environment represents a unique challenge for biological
      systems that have evolved against gravitational background. Ground-based and
      space research indicates that the developing nervous system is potentially
      affected by exposure to hyper/microgravity. With the construction of the orbiting
      International Space Station long-term research on the nervous system will be
      possible. With this perspective, we started ground-based studies to characterize
      mouse behavioral responses to rotation-induced 2 g hypergravity, using a custom
      made centrifuge device. Brain levels of nerve growth factor (NGF) and brain
      derived neurotrophic factor (BDNF) as well as NGF and BDNF expression and mast
      cell distribution in heart and lung, were evaluated and correlated with the
      changes in mouse behavior upon hypergravity exposure. Hypergravity strongly
      affected the spontaneous activity of the animals, selectively modifying mouse
      behavioral repertoire. Such changes were mainly related to variations in brain
      levels of NGF, while BDNF was slightly affected, thus confirming a role for these
      neurotrophins in neuronal plasticity underlying experience-induced
      neurobehavioral changes. Moreover, gender differences were observed in both
      behavioral and neurobiological responses to hypergravity. These results indicate
      that changes in the gravitational environment might represent a useful tool to
      investigate the neurobiological and behavioral responses to stressors and may
      provide insights into the mechanisms underlying development and plasticity of
      nervous system in brain, heart, and lung.

PMID- 14699966
TI  - Neurotrophic factors in Huntington's disease.
AB  - Huntington's disease is a neurodegenerative disorder characterized by the
      selective loss of striatal neurons and, to a lesser extent, cortical neurons. The
      neurodegenerative process is caused by the mutation of huntingtin gene. Recent
      studies have established a link between mutant huntingtin, excitotoxicity and
      neurotrophic factors. Neurotrophic factors prevent cell death in degenerative
      processes but they can also enhance growth and function of neurons that are
      affected in Huntington's disease. The endogenous regulation of the expression of
      neurotrophic factors and their receptors in the striatum and its connections can
      be important to protect striatal cells and maintains basal ganglia connectivity.
      The administration of exogenous neurotrophic factors, in animal models of
      Huntington's disease, has been used to characterize the trophic requirements of
      striatal and cortical neurons. Neurotrophins, glial cell line-derived
      neurotrophic factor family members and ciliary neurotrophic factor have shown a
      potent neuroprotective effects on different neuronal populations of the striatum.
      Furthermore, they are also useful to maintain the integrity of the
      corticostriatal pathway. Thus, these neurotrophic factors may be suitable for the
      development of a neuroprotective therapy for neurodegenerative disorders of the
      basal ganglia.

PMID- 14699967
TI  - Neural crest development and neuroblastoma: the genetic and biological link.
AB  - Neuroblastoma is one of the most common pediatric solid tumors originating from
      the sympathoadrenal lineage of neural crest. The tumor shows extremely different
      clinical phenotypes such as spontaneous regression on one hand and aggressive
      growth on the other hand. The different biological behavior of neuroblastoma
      appears to be determined by the genetic abnormalities including amplification of
      MYCN oncogene, DNA ploidy and some allelic imbalances. However, the spontaneous
      regression of neuroblastoma mimics the programmed cell death normally occurring
      in developing sympathetic cells expressing both TrkA tyrosine kinase A and p75NTR
      neurotrophin receptor. Indeed, TrkA expression is the most important factor
      related to the induction of tumor cell differentiation and/or programmed cell
      death because without its expression spontaneous regression of neuroblastoma
      never occurs. Thus, the enigmatic clinical behaviors of neuroblastoma are
      strictly linked to the molecular mechanism of neural crest development.

PMID- 14699968
TI  - Neurotrophin-3 in the development of the enteric nervous system.
AB  - To date, the only neurotrophin that has been shown to influence the development
      of the enteric nervous system (ENS) is neurotrophin-3 (NT-3). NT-3 plays an
      essential role in the development of both the neural-crest-derived peripheral
      nervous system and the central nervous system (i.e., Chalazonitis, 1996, Mol.
      Neurobiol., 12: 39-53; Sieber-Blum, 1999, Neurotrophins and the Neural Crest, CRC
      Press, Boca Raton). This review integrates data obtained from our laboratory and
      from our collaboration with other investigators that demonstrate a late-acting
      role for NT-3 in the development of enteric neurons in vitro and in vivo. Studies
      of the biological actions of NT-3 on enteric neuronal precursors in vitro
      demonstrate that NT-3 acts directly on the precursor cells and that it also acts
      in combination with other neurotrophic factors such as glial cell line-derived
      neurotrophic factor and a ciliary neurotrophic factor-like molecule, to promote
      the survival and differentiation of enteric neurons and glia. Importantly, bone
      morphogenetic protein-2 (BMP-2) and BMP-4, members of the transforming growth
      factor-beta (TGF-beta) superfamily, regulate the onset of action of NT-3 during
      fetal gut development. Analyzes performed on mice deficient in the genes encoding
      NT-3 or its transducing tyrosine kinase receptor, TrkC, and conversely on
      transgenic mice that overexpress NT-3 substantiate a physiological role for NT-3
      in the development and maintenance of a subset of enteric neurons. There is loss
      of neurons in both the myenteric and submucosal plexuses of mice lacking NT
      3/TrkC signaling and selective hyperplasia in the myenteric plexus of mice
      overexpressing NT-3. Analyzes performed on transgenic mice that overexpress
      noggin, a specific BMP-4 antagonist, show significant decreases in the density of
      TrkC-expressing neurons but significant increase in overall neuronal density of
      both plexuses. Conversely, overexpression of BMP-4 is sufficient to produce, an
      increase in the proportion of TrkC-expressing neurons in both plexuses. Overall,
      our data point to a regulatory role of BMP-4 in the responses of subsets of
      myenteric and submucosal neurons to NT-3. NT-3 is required for the
      differentiation, maintenance and proper physiological function of late-developing
      enteric neurons that are important for the control of gut peristalsis.

PMID- 14699969
TI  - Neurotrophins in the ear: their roles in sensory neuron survival and fiber
      guidance.
AB  - We review the history of neurotrophins in the ear and the current understanding
      of the function of neurotrophins in ear innervation, development and maintenance.
      Only two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin
      3 (NT-3), and their receptors, tyrosine kinase B (TrkB) and TrkC, appear to
      provide trophic support for inner ear sensory neuron afferents. Mice lacking
      either both receptors or both ligands lose essentially all sensory innervation of
      targets in the vestibular and auditory systems of the ear. Analyzes of single
      mutants show less complete and differential effects on innervation of the
      different sensory organs within the ear. BDNF and TrkB are most important for
      survival of vestibular sensory neurons whereas NT-3 and TrkC are most important
      for survival of cochlear sensory neurons. The largely complementary roles of BDNF
      to TrkB and NT-3 to TrkC signaling do not reflect specific requirements for
      innervation of different classes of hair cells. Most neurons express both
      receptors. Instead, the losses observed in single mutants are related to the
      spatio-temporal expression pattern of the two neurotrophins. In an area where
      only one neurotrophin is expressed at a particular time in development, the other
      neurotrophin is not present to compensate for this absence, resulting in death of
      neurons innervating that region. Decisive evidence for this suggestion is
      provided by transgenic mice in which the BDNF coding region has been inserted
      into the NT-3 gene, resulting in expression of BDNF instead of NT-3. The
      expression of BDNF in the spatio-temporal pattern of NT-3 results in survival of
      almost all neurons that are normally lost in the NT-3 mutant. Thus, BDNF and NT-3
      have a high level of functional equivalence for inner ear sensory neuron
      survival. Further analysis of the patterns of afferent fiber losses in mutations
      that do not develop differentiated hair cells shows that the expression of
      neurotrophins is remarkably strong and can support afferent innervation. Indeed,
      BDNF may be one of the earliest genes expressed selectively in hair cells and it
      appears to be regulated somewhat independently of the genes needed for hair cell
      differentiation.

PMID- 14699970
TI  - Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a
      role for NGF and BDNF in cardiovascular disease?
AB  - The development of atherosclerotic cardiovascular disease is a common comorbidity
      in patients with the metabolic syndrome, a concurrence of cardiovascular risk
      factors in one individual. While multiple growth factors and adipokines are
      identified in atherosclerotic lesions, as well as neurotrophins implicated in
      both cardiac ischemia and lipid and glucose metabolism, the potential role of
      neurotrophins in human coronary atherosclerosis and in the metabolic syndrome
      still remains to be elucidated. Here we describe and discuss our results that
      represent a novel attempt to study the cardiovascular and metabolic biology of
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast
      cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin
      receptor (p75NTR) and the number of MC were correlatively examined in coronary
      vascular wall and in the surrounding subepicardial adipose tissue, obtained from
      autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed
      the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from
      abdominal subcutaneous adipose tissue in patients with a severe form of the
      metabolic syndrome. The results demonstrate that NGF levels are decreased in
      atherosclerotic coronary vascular tissue but increased in the subepicardial
      adipose tissue, whereas both tissues express a greater number of MC and a
      stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome
      patients display a significant hyponeurotrophinemia and an increased number of
      adipose MC; the later correlates with elevated plasma leptin levels. In effect,
      we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC
      in both coronary vascular and subepicardial adipose tissue in human coronary
      atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels
      and an elevated amount of plasma leptin and adipose MC in metabolic syndrome
      patients. Together our findings suggest that neuroimmune mediators such as NGF,
      BDNF, leptin and MC may be involved in the development of cardiovascular disease
      and related disorders.

PMID- 14699971
TI  - Neurotrophins in spinal cord nociceptive pathways.
AB  - Neurotrophins are a well-known family of growth factors for the central and
      peripheral nervous systems. In the course of the last years, several lines of
      evidence converged to indicate that some members of the family, particularly NGF
      and BDNF, also participate in structural and functional plasticity of nociceptive
      pathways within the dorsal root ganglia and spinal cord. A subpopulation of small
      sized dorsal root ganglion neurons is sensitive to NGF and responds to peripheral
      NGF stimulation with upregulation of BDNF synthesis and increased anterograde
      transport to the dorsal horn. In the latter, release of BDNF appears to modulate
      or even mediate nociceptive sensory inputs and pain hypersensitivity. We
      summarize here the status of the art on the role of neurotrophins in nociceptive
      pathways, with special emphasis on short-term synaptic and intracellular events
      that are mediated by this novel class of neuromessengers in the dorsal horn.
      Under this perspective we review the findings obtained through an array of
      techniques in naive and transgenic animals that provide insight into the
      modulatory mechanisms of BDNF at central synapses. We also report on the results
      obtained after immunocytochemistry, in situ hybridization, and monitoring
      intracellular calcium levels by confocal microscopy, that led to hypothesize that
      also NGF might have a direct central effect in pain modulation. Although it is
      unclear whether or not NGF may be released at dorsal horn endings of certain
      nociceptors in vivo, we believe that these findings offer a clue for further
      studies aiming to elucidate the putative central effects of NGF and other
      neurotrophins in nociceptive pathways.

PMID- 14699972
TI  - The role of neurotrophins in bronchial asthma: contribution of the pan
      neurotrophin receptor p75.
AB  - Allergic bronchial asthma is characterized by chronic inflammation of the
      airways, development of airway hyperreactivity and recurrent reversible airway
      obstruction. Target and effector cells responsible for airway hyperresponsiveness
      and airway obstruction include sensory and motor neurons as well as epithelial
      and smooth muscle cells. Although it is well established that the inflammatory
      process is controlled by T-helper-2 (Th2) cells, the mechanisms by which immune
      cells interact with neurons, epithelial cells or smooth muscle cells still remain
      uncertain. Due to growing evidence for extensive communication between neurons
      and immune cells, the mechanisms of this neuroimmune crosstalk in lung and
      airways of asthmatic patients are becoming the focus of asthma research.
      Neurotrophins represent molecules potentially responsible for regulating and
      controlling the crosstalk between the immune and peripheral nervous system. They
      are constitutively expressed by resident lung cells and produced in increasing
      concentrations by immune cells invading the airways under pathological
      conditions. Neurotrophins modify the functional activity of sensory and motor
      neurons, leading to enhanced and altered neuropeptide and tachykinin production.
      These effects are defined as neuronal plasticity. The consequences are the
      development of neurogenic inflammation.

PMID- 14699973
TI  - Neurotrophins and neurotrophin receptors in allergic asthma.
AB  - The neurotrophins nerve growth factor, brain-derived neurotrophic factor,
      neurotrophin-3 (NT-3) and NT-4 play a pivotal role in the development of the
      nervous system. Despite their well-known effects on neurons, elevated
      neurotrophin concentrations have been observed under pathological conditions in
      sera of patients with inflammatory disorders. Patients with asthma feature both
      airway inflammation and an abnormal airway reactivity to many unspecific stimuli,
      referred to as airway hyperresponsiveness, which is, at least partly, neuronally
      controlled. Interestingly, these patients show increased levels of neurotrophins
      in the blood as well as locally in the lung. It has been demonstrated that
      neurotrophin release from immune cells is triggered by allergen contact. The
      presence of neurotrophins and the neurotrophin receptors p75 (p75NTR), tyrosine
      kinase A (TrkA), TrkB and TrkC have been described in several immune cells. There
      is strong evidence for an involvement of neurotrophins in regulation of
      hematopoiesis and, in addition, in modulation of immune cell function in mature
      cells circulating in blood or resting in lymphatic organs and peripheral tissues.
      The aim of this review is to demonstrate possible roles of neurotrophins during
      an allergic reaction in consideration of the temporospatial
      compartimentalization.

PMID- 14699974
TI  - Nerve growth factor and wound healing.
AB  - The wound healing process following tissue injury consists of a highly regulated
      sequence of events. Besides many biological activities on both neuronal and
      nonneuronal cells, nerve growth factor (NGF) has been proposed as an important
      component of wound healing and tissue repair process in vivo and in vitro. For
      example, NGF accelerates the rate of wound healing both in normal mice and
      healing-impaired diabetic mice, and has a potent pharmacological effect in the
      treatment for ulcer of the skin and cornea in humans. This review summarizes the
      evidence for the role of NGF in wound healing and tissue repair, and introduces
      its clinical utility as a therapeutic agent for various diseases.

PMID- 14699975
TI  - Interactions between the cells of the immune and nervous system: neurotrophins as
      neuroprotection mediators in CNS injury.
AB  - Inflammatory processes in the central nervous system (CNS) are considered
      neurotoxic, although recent studies suggest that they also can be beneficial and
      confer neuroprotection (neuroprotective autoimmunity). Cells from the immune
      system have been detected in CNS injury and found to produce and secrete a
      variety of neurotrophins such as NGF, BDNF, NT-3 and NT-4/5, and to express
      (similarly to neuronal cells), members of the tyrosine kinase (Trk) receptor
      family such as TrkA, TrkB and TrkC. Indeed, autocrine and paracrine interactions
      are observed at the site of CNS injury, resulting in a variety of homologic
      heterologic modulations of immune and neuronal cell function. The end result of
      the inflammatory process, neurotoxicity and/or neuroprotection, is a function of
      the fine balance between the two cellular systems, i.e., of the complex signaling
      relationships between anti-inflammatory neuroprotective factors (neurotrophins
      and other chemical mediators) and proinflammatory neurotoxic factors (TNF, free
      radicals, certain cytokines, etc.). Autoimmune neuroprotection is a novel
      therapeutic approach aimed at shifting the balance between the immune and
      neuronal cells towards survival pathways in a variety of CNS injuries. This
      review focuses on data supporting this concept and its future therapeutical
      implications for optic nerve injury and multiple sclerosis.

PMID- 14699976
TI  - Role of nerve growth factor and other trophic factors in brain inflammation.
AB  - Inflammation in the brain is a double-edged process that may be beneficial in
      promoting homeostasis and repair, but can also result in tissue injury through
      the damaging potential of inflammatory mediators. Thus, control mechanisms that
      minimize the extent of the inflammatory reaction are necessary in order to help
      preserve brain architecture and restore function. The expression of neurotrophic
      factors such as nerve growth factor (NGF) is increased after brain injury, in
      part mediated by effects on astrocytes of pro-inflammatory mediators and
      cytokines produced by immune cells. Conversely, cells of the immune system
      express NGF receptors, and NGF signaling modulates immune function. Multiple
      sclerosis (MS) and the disease model experimental autoimmune encephalomyelitis
      are neurodegenerative disorders whereby chronic destruction of the brain
      parenchyma results from an autoaggressive, immune-mediated inflammatory process
      and insufficient tissue regeneration. Here, we review evidence indicating that
      the increased production of NGF and other trophic factors in central nervous
      system (CNS) during these diseases can suppress inflammation by switching the
      immune response to an anti-inflammatory, suppressive mode in a brain-specific
      environment. Thus, trophic factors networks in the adult CNS not only protects
      axons and myelin but appear to also actively contribute to the maintenance of the
      brain immune privilege. These agents may represent good targets for therapeutic
      intervention in MS and other chronic CNS inflammatory diseases.

PMID- 14699978
TI  - Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis.
AB  - A contributing role of neurogenic inflammation has provided a new dimension in
      understanding the pathogenesis of various cutaneous and systemic inflammatory
      diseases such as atopic dermatitis, urticaria, rheumatoid arthritis, ulcerative
      colitis and bronchial asthma. Several critical observations, such as (i)
      psoriasis resolves at sites of anaesthesia, (ii) neuropeptides are upregulated,
      and (iii) there is a marked proliferation of terminal cutaneous nerves in
      psoriatic plaques, encouraged us to search for a mechanism of neural influence in
      inflammation and inflammatory diseases. In immunohistochemical studies, we found
      that keratinocytes in lesional and nonlesional psoriatic tissue express high
      levels of nerve growth factor (NGF) and that there is a marked upregulation of
      NGF receptors, p75 neurotrophin receptor (p75NTR) and tyrosine kinase A (TrkA),
      in the terminal cutaneous nerves of psoriatic lesions. As keratinocytes of
      psoriatic plaques express increased levels of NGF, it is likely that murine
      nerves will promptly proliferate into the transplanted plaques on a severe
      combined immunodeficient mouse. Indeed, we have noted marked proliferation of
      nerve fibers in transplanted psoriatic plaques compared with the few nerves in
      transplanted normal human skin. By double label immunofluorescence staining, we
      have further demonstrated that in these terminal cutaneous nerves there is a
      marked upregulation of neuropeptides, such as substance P and calcitonin gene
      related protein. These observations, as well as recent findings about NGF-induced
      chemokine expression in keratinocytes, further substantiate a role of the NGF
      p75NTR-TrkA system in the inflammatory process of psoriasis. Currently, we are
      evaluating antagonists to selected neuropeptides and NGF/receptors, with the
      expectation of identifying pharmacological agents to counter neurogenic
      inflammation in psoriasis.

PMID- 14699977
TI  - Remyelination in multiple sclerosis: a new role for neurotrophins?
AB  - Multiple sclerosis (MS) is a common neurological disease, which affects young
      adults. Its course is unpredictable and runs over decades. It is considered as an
      autoimmune disease, and is neuropathologically characterized by demyelination,
      variable loss of oligodendroglial cells, and axonal degeneration. Demyelination
      provides a permitting condition for axonal degeneration, which seems to be
      causative of permanent neurological deficits. Hence, the current treatment, which
      works preferentially immunmodulatory, should be complemented by therapeutics,
      which improves remyelination not only for restoring conduction velocity but also
      for preventing an irreversible axonal damage. One strategy to achieve this aim
      would be to promote remyelination by stimulating oligodendroglial cells remaining
      in MS lesions. While central nervous system neurons were already known to respond
      to neurotrophins (NT), interactions with glial cells became apparent more
      recently. In vitro and in vivo studies have shown that NT influence
      proliferation, differentiation, survival, and regeneration of mature
      oligodendrocytes and oligodendroglial precursors in favor of a myelin repair. Two
      in vivo models provided direct evidence that NT can improve remyelination. In
      addition, their neuroprotective and anti-inflammatory role would support a
      repair. Hence, a wealth of data point to NT as promising therapeutical
      candidates.

PMID- 14699979
TI  - Nerve growth factor: from animal models of cholinergic neuronal degeneration to
      gene therapy in Alzheimer's disease.
AB  - Over the last 20 years it has been recognized that neurotrophic factors
      profoundly influence the development of the nervous system and have the potential
      to modify disease processes in the adult nervous system. The ability of nervous
      system growth factors to prevent or reduce neuronal degeneration in animal models
      of neurodegenerative diseases has led to several clinical trials. One of the main
      obstacles to the success of these trials has been the method of growth factor
      delivery: sufficiently high doses of neurotrophic factors must be achieved in the
      target region of the brain to efficiently modify disease processes, but delivery
      must be restricted to specific brain regions to prevent adverse effects. Recent
      advances in molecular medicine have made gene therapy in the nervous system a
      potentially realistic approach for the delivery of therapeutic molecules such as
      growth factors. As an alternative to conventional drug delivery, several gene
      therapy trials for the treatment of central nervous system diseases have started
      or will start in the near future. This chapter reviews the development of
      neurotrophic factor gene therapy for neurodegenerative diseases focusing on the
      therapeutic potential of nerve growth factor in Alzheimer's disease, currently
      the subject of a phase I clinical trial.

PMID- 14699980
TI  - Viral vector-mediated gene transfer of neurotrophins to promote regeneration of
      the injured spinal cord.
AB  - Injuries to the adult mammalian spinal cord often lead to severe damage to both
      ascending (sensory) pathways and descending (motor) nerve pathways without the
      perspective of complete functional recovery. Future spinal cord repair strategies
      should comprise a multi-factorial approach addressing several issues, including
      optimalization of survival and function of spared central nervous system neurons
      in partial lesions and the modulation of trophic and inhibitory influences to
      promote and guide axonal regrowth. Neurotrophins have emerged as promising
      molecules to augment neuroprotection and neuronal regeneration. Although
      intracerebroventricular, intrathecal and local protein delivery of neurotrophins
      to the injured spinal cord has resulted in enhanced survival and regeneration of
      injured neurons, there are a number of drawbacks to these methods. Viral vector
      mediated transfer of neurotrophin genes to the injured spinal cord is emerging as
      a novel and effective strategy to express neurotrophins in the injured nervous
      system. Ex vivo transfer of neurotrophic factor genes is explored as a way to
      bridge lesions cavities for axonal regeneration. Several viral vector systems,
      based on herpes simplex virus, adenovirus, adeno-associated virus, lentivirus,
      and moloney leukaemia virus, have been employed. The genetic modification of
      fibroblasts, Schwann cells, olfactory ensheathing glia cells, and stem cells,
      prior to implantation to the injured spinal cord has resulted in improved
      cellular nerve guides. So far, neurotrophic factor gene transfer to the injured
      spinal cord has led to results comparable to those obtained with direct protein
      delivery, but has a number of advantages. The steady advances that have been made
      in combining new viral vector systems with a range of promising cellular
      platforms for ex vivo gene transfer (e.g., primary embryonic neurons, Schwann
      cells, olfactory ensheating glia cells and neural stem cells) holds promising
      perspectives for the development of new neurotrophic factor-based therapies to
      repair the injured nervous system.

PMID- 14699981
TI  - Neurotrophic factors and their receptors in human sensory neuropathies.
AB  - Neurotrophic factors may play key roles in pathophysiological mechanisms of human
      neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory
      fibers and regulates nociception. This review focuses on sensory dysfunction and
      the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the
      NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in
      congenital insensitivity to pain and anhidrosis; these are likely to be partial
      loss-of-function mutations, as axon-reflex vasodilatation and sweating can be
      elicited albeit reduced, suggesting rhNGF could restore nociception in some
      patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous
      hypoalgesia even with inflammation and rhNGF may restore sensation, as spared
      nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early
      human diabetic neuropathy skin, in correlation with dysfunction of nociceptor
      fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration.
      Clinical trials have been disappointed, probably related to difficulty delivering
      adequate doses and need for multiple trophic factors. NGF and glial cell line
      derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and
      neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was
      significantly lower in early diabetic neuropathy skin compared to controls, for
      NGF (P < 0.02), BDNF (P < 0.05), NT-3 (P < 0.05), GDNF (< 0.02), but not NT4/5,
      Trk A or p75 neurotrophin receptor (all P > 0.05). Posttranslational
      modifications of mature and pro-NGF may also affect bioactivity and
      immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like
      molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF
      levels are acutely reduced in injured nerve trunks, neuropathic patients with
      chronic skin hyperalgesia and allodynia show marked local increases of NGF
      levels; here anti-NGF agents may provide analgesia. Physiological combinations of
      NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel
      'homeostatic' approach to prevent the development and ameliorate intractable
      neuropathic pain (e.g., at painful amputation stumps).

PMID- 14699982
TI  - Epithelial growth control by neurotrophins: leads and lessons from the hair
      follicle.
AB  - Neurotrophins (NTs) exert many growth-regulatory functions beyond the nervous
      system. For example, murine hair follicles (HF) show developmentally and spatio
      temporally stringently controlled expression of NTs, including nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3),
      and NT-4, and their cognate receptors, tyrosine kinase A-C (TrkA-C) and p75
      neurotrophin receptor (p75NTR). Follicular NT and NT receptor expression exhibit
      significant, hair cycle-dependent fluctuations on the gene and protein level,
      which are mirrored by changes in nerve fiber density and
      neurotransmitter/neuropeptide content in the perifollicular neural networks. NT
      3/TrkC and NGF/TrkA signaling stimulate HF development, while NT-3, NT-4 and BDNF
      inhibit the growth (anagen) of mature HF by the induction of apoptosis-driven HF
      regression (catagen). p75NTR stimulation inhibits HF development and stimulates
      catagen. Since the HF is thus both a prominent target and key peripheral source
      of NT, dissecting the role of NTs in the control of HF morphogenesis and cyclic
      remodeling provides a uniquely accessible, and easily manipulated, clinically
      relevant experimental model, which has many lessons to teach. Given that our most
      recent data also implicate NTs in human hair growth control, selective NT
      receptor agonists and antagonists may become innovative therapeutic tools for the
      management of hair growth disorders (alopecia, effluvium, hirsutism). Since,
      however, the same NT receptor agonists that inhibit hair growth (e.g., BDNF, NT
      4) can actually stimulate epidermal keratinocyte proliferation, NT may exert
      differential effects on defined keratinocyte subpopulations. The studies reviewed
      here provide new clues to understanding the complex roles of NT in epithelial
      tissue biology and remodeling in vivo, and invite new applications for synthetic
      NT receptor ligands for the treatment of epithelial growth disorders, exploiting
      the HF as a lead model.

PMID- 14699983
TI  - Nerve growth factor, human skin ulcers and vascularization. Our experience.
AB  - Cutaneous wound is known to elicit a series of typical cellular responses that
      include clotting, inflammatory infiltration, reepithelialization, the formation
      of granulation tissue, including new blood vessel, followed by tissue remodeling
      and wound contraction. The regulatory molecules implicated in these events are
      not well known. Neurotrophins and their receptors are trophic factors that are
      known to play important roles in cutaneous tissues, nerve development and
      reconstruction after injury. Among the neurotrophins, the nerve growth factor
      (NGF) was one of the earliest used for clinical studies. NGF has been tested for
      potential therapeutic application in neuropathies of the central and peripheral
      nervous system and more recently in human corneal and cutaneous ulcers. Here, I
      present and discuss data obtained in the last few years on the healing action of
      NGF in human and domestic animal skin ulcers.

PMID- 14699984
TI  - The nerve growth factor and the neuroscience chess board.

PMID- 14699985
TI  - Perspectives. Health care in forefront of security needs, say analysts.

PMID- 14699986
TI  - Reducing major vascular events among VA primary care patients: an extraordinary
      opportunity.
AB  - Data from randomized trials document that the frequency of major vascular events
      can be significantly reduced by lowering serum cholesterol and systolic blood
      pressure in high-risk patients. The recent publication of the Heart Protection
      Study (HPS) provided randomized trial evidence to support the recommendation of
      the National Cholesterol Education Program Adult Treatment Panel III to broaden
      statin use to include patients whose risk for a coronary event is equivalent to
      that among patients with manifest coronary artery disease, such as those with
      diabetes or cerebral, aortic, or peripheral vascular disease. Similarly, recent
      meta-analyses of hypertension trials provide us precise estimates of the benefits
      of lowering blood pressure. Risk and risk reduction data from these trials were
      applied to 153,305 Veterans Health Administration primary care patients to assess
      the health impact and costs of lowering cholesterol and blood pressure more
      aggressively in this population. Based on the results, it was estimated that
      98,598 major vascular events might be prevented and $302,074,587 saved over 5
      years if all patients were treated according to the HPS criteria and the
      recommendations of the Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. It is
      anticipated that achieving these goals will not be possible without significant,
      innovative system changes, such as disease management programs with electronic
      chart abstraction to identify patients who do not meet these recommendations.

PMID- 14699987
TI  - Lessons learned from recent lipid-lowering trials: why physicians should change
      clinical practice.
AB  - In the past decade there has been an explosion of data on the beneficial role of
      cholesterol reduction in the prevention and treatment of cardiovascular disease
      (CVD). While earlier clinical trials focused primarily on patient populations
      with very high cholesterol levels, more recent studies have also included
      individuals with somewhat lower, or "average," cholesterol levels. What is
      becoming clearer is that many patients with so-called "average" cholesterol
      levels may benefit from cholesterol reduction therapy to reduce the risk of
      cardiovascular events. Recent studies, such as the Heart Protection Study,
      provide further evidence for cholesterol reduction in the prevention and
      treatment of CVD and offer valuable lessons about cardiovascular risk reduction.

PMID- 14699988
TI  - Specialized tests for hemostasis.

PMID- 14699989
TI  - George E. Steares keeps an eye on Olympus' Scientific Equipment Group. Interview
      by Dottie Dunham.

PMID- 14699990
TI  - Doing more with less in the lab.
AB  - Automation offers laboratories the ability to improve patient care, enhance
      client and employee satisfaction, and increase workload capacity while
      maintaining a cost-effective department. "The overall objective of any
      organization's automation project is simple--to do more with less, better,"
      states Davis. "We know our future is on the information systems side," Clarke
      states. "Vendors' investment in the development and creativity of automation is
      what is going to drive the future of the laboratory." "Implementing the
      automation solution was absolutely the right thing to do for Sacred Heart
      Health," says Wright. "With the transition complete, we are pleased with the
      results. All we want now is more automation that will enable us to do even more
      with what we have."

PMID- 14699991
TI  - Where the heroes are: a tribute to military MLTs.

PMID- 14699992
TI  - Stick to OSHA rules.

PMID- 14699993
TI  - Long distance PCR in detection of inversion mutations of F8C gene in hemophilia A
      patients.
AB  - In the present paper, the experience with detection of intron 22 inversion of F8C
      gene in severe hemophilia A patients using a recently described long-distance PCR
      (LD-PCR) method was reported. To test the sensitivity and the specifity of the LD
      PCR, analysis of 46 DNA samples of patients and their family members, previously
      tested by Southern hybridization, was performed. In addition, 16 DNA samples of
      severe hemophilia A patients in which causative mutation was unknown, were
      included in analysis. Four-primers, P, Q, A&B, which are able to differentiate
      between the affected males with or without the inversion, and in female carriers,
      were used in LD-PCR. Two primers, P&Q, are located within the F8C gene flanking
      int22h1. Two further primers, A&B, flank int22h2 and int22h3, extragene homologs
      of int22h1. Nine combinations of four primers were used to identify the optimal
      one. Four-primers (P, Q, A&B), three-primers (P,Q & B;P, A & B; A, B & Q;P, Q &
      A) and two-primers (A & B; P & Q; A & Q; P & B) PCR amplifications were performed
      in the hemophilia A patients as well as in obligate carriers DNA samples.
      Successful amplification required introduction of some modifications of the
      original protocol. The most reproducible and uniform results were obtained using
      two-primers PCR, performed in four single reactions. Thus, a total of 46 DNA
      samples, 22 were hemizygous for inversion, 6 without the inversion, 14 carriers
      and 4 non-carriers of inversion. Perfect correlation between genotypes determined
      using Southern hybridization and LD-PCR was achieved. The optimalized two-primers
      LD-PCR protocol was used for analysis of 16 DNA samples of severe hemophilia A
      patients with unknown mutation. Ten cases of inversions and six cases without
      them were detected. Thus in additional 10 severe hemophilic patients DNA
      diagnosis was completed. The most successful and reproducible results were
      obtained performing four single LD-PCR reactions with combinations of two-primers
      A & B; P & Q; A&Q, and P&B in each DNA sample and this approach is recommended
      for routine using in clinical practice.

PMID- 14699994
TI  - The unrealized potential of prenatal care. A population health approach.
AB  - To review the scientific evidence behind the traditional view that prenatal care
      improves pregnancy outcomes. The literature published in English between 1965 and
      2002 was searched for relevant studies and opinions on prenatal care outcomes. As
      search engine we used the MEDLINE bibliographic database, employing a combination
      of keywords, including pregnancy, prenatal care and outcomes. Editorials,
      proceedings of meetings and reviews, were included in the analysis. This review
      was not intended to be a systematic or exhaustive review of the literature on
      prenatal care. The significant heterogeneity of the retrieved papers made any
      aggregation impossible. In each of the reviewed studies we assessed the
      methodologic aspects and validity of conclusions, using established criteria for
      the evaluation of prenatal interventions. Our processing of editorials and other
      personal opinions was conducted with the intention to draw the line between
      statements based on scientific evidence and speculative, emotional or traditional
      concepts. Outcomes research related to prenatal care is marred by methodologic
      flaws and conceptual problems. While traditional prenatal protocols are based on
      an individual-centered medical care system, the outcomes are measured using
      population-based parameters. Interventions capable of improving maternal and
      neonatal outcomes at the population level are more likely to be social and
      economic rather than health interventions case by case.

PMID- 14699995
TI  - Prevalence of birth defects and rubella infection in pregnant women in Gansu,
      west China. A survey.
AB  - OBJECTIVE: To determine the incidence, disease types, sequence of birth defects
      and prevalence of IgG and IgM in rubella infection in prepregnancy and pregnancy
      within 3 months in Gansu, People's Republic of China, and to determine a baseline
      of birth defects for an intervention project on birth defects in Gansu. STUDY
      DESIGN: Liveborn and stillborn infants from January 1, 2001, to January 1, 2002,
      and 518 prepregnant and 373 pregnant women in 3 months in 4 counties, including
      42 communities selected random by stratification cluster sampling for a survey on
      the economic and geographic features in the province in October 2001 were
      investigated. Every infant born in the study period was surveyed. The types of
      birth defects were classed by standard diagnostic codes (ICD-9). Five-milliliter
      blood samples were obtained from every prepregnant and pregnant women. Rubella
      IgG and IgM were measured by enzyme-linked immunosorbent assay. RESULTS: The
      overall number of birth defects in Gansu was 102 (16.35%). The incidence of birth
      defects by sex was 62 males (18.55%) and 40 females (13.9%). The types of birth
      defects were neural tube defect, 44 cases (7.07%); limb defects, 13 (2.09%);
      cleft lip and palate, 5 (0.8%); and Down syndrome, 3 (0.48%). Low birth weight
      occurred in 31 cases (4.98%). The seasonal incidence birth defects was spring, 24
      cases (23.52%); summer, 31 (30.39%); autumn, 26 (25.49%); and winter, 21
      (20.59%). There were significant differences between 4 counties. The death rate
      from birth defects was 48 cases (47.06%). The positive rates of IgM and IgG of
      rubella infection of prepregnant women were, respectively, 5.02% and 83.78%; in
      pregnant women they were, respectively, 2.41% and 86.33%. The seropositive rate
      of rubella infection of prepregnancy was 88.80%; that of pregnancy was 88.74%.
      CONCLUSION: The rate of rubella infection in prepregnant and pregnant women
      within 3 months in Gansu was one of the highest in the People's Republic of
      China. The rate of birth defects in Gansu was one of much higher than in the
      People's Republic of China as a whole.

PMID- 14699996
TI  - [Pelvic absymmetry. 1949].

PMID- 14699997
TI  - Development of processes for environmental protection based on self-propagating
      reactions.
AB  - The possibility of exploiting self-propagating reactions for environmental
      protection is discussed in this paper. In particular, results obtained at the
      laboratory scale and related to the fixation and consolidation of high level
      radioactive wastes, the recycling of silicon sludge and aluminum dross produced
      by semiconductor industries and aluminum foundries, the treating and recycling of
      a highly toxic solid waste from electrolytic zinc plants, and the degradation of
      chlorinated aromatics, are examined with particular emphasis on the latter case.
      Specifically, the self-propagating destruction of hexachlorobenzene and 2-(2-4
      dichlorophenoxy)-propanoic acid with calcium hydride as reductive substrate is
      demonstrated. In fact, the heat liberated by the reactions involved is large
      enough to guarantee the self-sustaining character of the process within a wide
      range of reactants compositions. Moreover, no residual chlorinated organic
      compounds were found in the final solid product. Some reactor engineering
      aspects, as well as other significant future scientific and technological issues,
      are also addressed in view of large-scale applicability of processes based on
      self-propagating reactions. To date, the batch reactor technology seems to be
      more easily applicable, although the use of continuous reactors is not excluded
      in the next future.

PMID- 14699998
TI  - Chemical recycling of poly(ethylene terephthalate) (PET) by hydrolysis and
      glycolysis.
AB  - In this paper we review an interesting method of PET recycling, i.e. chemical
      recycling; it is based on the concept of depolymerizing the condensation polymer
      through solvolytic chain cleavage into low molecular products which can be
      purified and reused as raw materials for the production of high-quality chemical
      products. In this work our attention is confined to the hydrolysis (neutral, acid
      and alkaline) and glycolysis processes of PET chemical recycling; operating
      conditions and mechanism of each method are reported and described. The neutral
      hydrolysis has an auto accelerating character; two kinetic models have been
      proposed: an half-order and a second order kinetic model. The acid hydrolysis
      could be explained by a modified shrinking core model under chemical reaction
      control and the alkaline hydrolysis by a first-order model with respect to
      hydroxide ion concentration. To describe glycolysis, two different kinetic models
      have been proposed where EG can act or not as internal catalyst. Further
      experimental and theoretical investigations are required to shed light on the
      promising processes of PET chemical recycling reviewed in this work.

PMID- 14699999
TI  - Influence of light polarization on dynamics of continuous-wave-pumped Raman fiber
      lasers.
AB  - The dynamical behavior of cw-pumped Raman fiber lasers is studied experimentally.
      Lasers made of standard single-mode fibers are found to present unstable
      behaviors depending on the states of polarization of the Stokes and pump fields.
      On the contrary, lasers made of polarization-maintaining fibers are found to be
      always stable. The observed behaviors suggest that birefringence- and Kerr
      induced changes in polarization states dramatically affect Raman fiber lasers
      dynamics.

PMID- 14700000
TI  - [Inpatient and ambulatory prevention of thromboembolism in surgery and
      perioperative medicine].

PMID- 14700002
TI  - [Techniques and complementary techniques. Endotracheal aspiration, bronchial
      brushing and bronchoalveolar lavage].
AB  - The aim of endotracheal aspiration is to eliminate secretions in patients with an
      artificial airway. All children with mechanical ventilation must undergo this
      procedure periodically. The frequency of aspiration depends on the type and
      quantity of the respiratory secretions and on the patient's clinical status.
      Aspiration should be performed by two people to maintain a greater degree of
      asepsis and to optimize stability of the airway and ventilation. Closed
      aspiration systems are available that allow aspiration without the need to
      disconnect the patient through a single probe that is constantly protected by a
      plastic sleeve and isolated from external environment. The most important risks
      of endotracheal aspiration are hypoxemia, mucosal injury, bronchospasm,
      arrhythmias, perforation of the airway with development of pneumothorax,
      accidental extubation, and infections. Bronchial brushing with a protected
      catheter and brochoalveolar lavage are used to analyze pulmonary infections.
      These techniques can be performed blind or through fibrobronchoscopy. They can
      also be used for the diagnosis of noninfectious pulmonary diseases such as
      alveolar proteinosis, alveolar hemorrhage or histiocytosis. Their adverse effects
      are similar to those of endotracheal aspiration.

PMID- 14700003
TI  - [Techniques and complementary techniques. Fiberoptic bronchoscopy in mechanically
      ventilated children].
AB  - Fiberoptic bronchoscopy can be performed at the patient's bedside. This technique
      allows direct visualization of the upper and lower airways up to the segmental
      and subsegmental bronchi. Its most frequent indications are airway examination ot
      evaluate damage produced by toxins or the endotracheal tube, patency of the
      endotracheal tube and extubation failure. It is also used to obtain
      microbiological samples, facilitate intubation when difficult, aspirate airway
      sections or mucus plugs, perform bronchoalveolar lavage and administer drugs.
      With prior preparation, adequate monitoring and sedation, material according to
      the size of the patient and correct techniques, there are few complications.
      However, the procedure can produce trauma and obstruction of the airway,
      bronchial hemorrhage, barotrauma, loss of alveolar recruitment, bronchospasm,
      hypoxemia, bradycardia, and bronchopulmonary infection.

PMID- 14700004
TI  - [Techniques and complementary techniques. Complementary treatments: nitric oxide,
      prone positioning and surfactant].
AB  - The management of hypoxic respiratory failure is based on oxygen delivery and
      ventilatory support with lung-protective ventilation strategies. Better
      understanding of acute lung injury have led to new therapeutic approaches that
      can modify the outcome of these patients. These adjunctive oxygenation strategies
      include inhaled nitric oxide and surfactant delivery, and the use of prone
      positioning. Nitric oxide is a selective pulmonary vasodilator that when inhaled,
      improves oxygenation in clinical situations such as persistent pulmonary
      hypertension of the newborn, pulmonary hypertension associated with congenital
      heart disease, and acute respiratory distress syndrome (ARDS). When applied early
      in ARDS, prone positioning improves distribution of ventilation and reduces the
      intrapulmonary shunt. The surfactant has dramatically decreased mortality caused
      by hyaline membrane disease in premature newborns, although the results have been
      less successful in ARDS. Greater experience is required to determine whether the
      combination of these treatments will improve the prognosis of these patients.

PMID- 14700005
TI  - Role of hepatic hemodynamic study in the evaluation of patients with cirrhosis.
AB  - BACKGROUND/AIMS: To evaluate the levels of hepatic venous pressure gradient
      (HVPG) in a population of cirrhotic patients, checking if the 12 mmHg level
      discriminates those who bleed by rupture of gastroesophageal varices and
      assessing the prognostic role of hepatic venous pressure gradient in the progress
      of these patients. METHODOLOGY: Eighty-three cirrhotic patients (mean age 52.9 +/
      10.1 years) were studied, 71.1% of whom were males. All patients performed a
      hepatic hemodynamic study to determine the hepatic venous pressure gradient.
      Patients were followed 16.6 +/- 16.02 months on average. RESULTS: Mean hepatic
      venous pressure gradient was 15.26 +/- 6.46 mmHg. The risk of bleeding was 50%
      for patients with hepatic venous pressure gradient below 12 mmHg and 76% (rr =
      1.52, p = 0.045) for those with hepatic venous pressure gradient above 12 mmHg.
      When patients were grouped according to outcome (death, shunt surgery,
      transplantation, or rebleeding), the mean hepatic venous pressure gradient (16.65
      +/- 6.71) was found to be significantly higher in these patients than in living
      patients without rebleeding (12.75 +/- 4.96), p = 0.014. However, the cutoff
      point of 16 mmHg failed to discriminate those patients with a worse prognosis.
      CONCLUSIONS: Hepatic venous pressure gradient determination can be used to
      identify those individuals with a higher risk of bleeding due to rupture of
      gastroesophageal varices, as well as those with a more reserved prognosis, even
      though the discriminative critical levels used suggest that its clinical
      usefulness is relative.

PMID- 14700006
TI  - The impact of diabetes on wound healing: implications of microcirculatory
      changes.
AB  - Diabetes is a well known cause of delayed wound healing yet the impact of
      diabetes on wound healing is not widely appreciated. This article examines the
      potential impact of diabetes-related microvascular disease on wound healing
      processes. The article reviews the available evidence and examines the practical
      consequences for nurses concerned with maintaining tissue viability.

PMID- 14700007
TI  - The use of honey for the treatment of two patients with pressure ulcers.
AB  - Chronic wounds such as pressure ulcers, leg ulcers and diabetic wounds are a
      common problem among older people and alternative methods to the current time
      consuming and costly practices of wound management in the nursing home need to be
      identified. To this end, we trialled the use of a honey alginate on two elderly
      males in our nursing home who were suffering from pressure ulcers (one on the
      ankle and one on the sacral region), to evaluate its effectiveness as a viable
      alternative to the current wound management practices in nursing homes. The use
      of honey resulted in a rapid and complete healing of both wounds. In addition,
      the antibacterial activity of honey had a deodorizing effect on the wounds and
      its anti-inflammatory actions helped reduce the level of pain. Similar healing
      results are also being observed in other patients with pressure-induced ulcers
      and as a result honey alginates are now being used as the 'standard' treatment
      for chronic wounds in our nursing home.

PMID- 14700008
TI  - Nicotine, CO and HCN: the detrimental effects  of smoking on wound healing.
AB  - During the 1960s, the Royal College of Physicians published its first report on
      smoking and health, concentrating on the association between smoking and long
      cancer, chronic obstructive pulmonary disease and heart disease (RCP, 2000). It
      was not until a decade later that the effects of smoking on wound healing were
      first reported (Mosely and Finseth, 1977). Although it is now widely accepted
      that smoking impairs wound healing, extensive studies have yet to be performed.
      Clinical practitioners have a role to deliver evidence-based care and provide
      smoking cessation programmes for patients with wounds. This article discusses
      three key toxins in cigarette smoke and research studies that have examined the
      effect of smoking on healing of acute wounds.

PMID- 14700009
TI  - Acute and maintenance treatment of bipolar mania: the role of atypical
      antipsychotics.
AB  - Bipolar disorder is a complex condition including depression, mania, and in many
      cases associated with comorbid anxiety symptoms and substance abuse. Mood
      stabilizers including lithium and divalproex have been considered standard
      therapy for the treatment of patients with bipolar disorder, but remission rates
      remain inadequate. Conventional antipsychotics have demonstrated efficacy for
      acute mania, but they appear to have little role in the maintenance treatment of
      bipolar disorder. Despite substantial evidence of efficacy and recent guideline
      recommendations, atypical antipsychotics remain underused for the treatment of
      bipolar disorder. Data from double-blind, controlled trials are available for a
      number of clinically meaningful efficacy measures, including improvement in manic
      symptoms, onset of action, response rates, remission rates, improvement in
      comorbid depressive symptoms, and induction/worsening of mania or depression.
      Atypical antipsychotics are effective both as alternatives to lithium or
      divalproex as monotherapy, or in combination with these mood stabilizers, in the
      acute and likely the maintenance treatment of mania. The atypical antipsychotics
      represent an effective and relatively safe addition to our armamentarium for the
      treatment of bipolar disorder.

PMID- 14700010
TI  - The role of atypical antipsychotics in bipolar depression and anxiety disorders.
AB  - Bipolar disorder is a complex condition that includes symptoms of mania,
      depression, and often anxiety. Diagnosing and treating bipolar depression is
      challenging, with the disorder often being diagnosed as unipolar depression. In
      addition, comorbid anxiety can be a significant detractor to successful outcomes,
      increasing symptom severity, frequency of episodes and suicide rates, and
      decreasing response to antidepressant therapy. Anxiety often precedes and hastens
      the onset of bipolar disorder, and a shared genetic etiology has been suggested.
      Studies have demonstrated the efficacy of atypical antipsychotics for the acute
      and maintenance treatment of mania. Evidence from studies in patients with
      treatment-resistant major depressive disorder and bipolar depression indicate
      that these agents may also have antidepressant effects. In open trials in
      patients with bipolar mania, risperidone therapy has led to significant
      reductions in depression scores compared with baseline. Reductions in depression
      scores in patients with bipolar mania have been significantly greater with
      olanzapine compared with placebo. In patients with bipolar depression, the
      combination of olanzapine and fluoxetine resulted in significant improvement in
      depression compared with olanzapine alone or placebo. Although little data are
      available on the effects of these agents on comorbid anxiety in patients with
      bipolar disorder, some atypical antipsychotics have demonstrated efficacy in
      patients with anxiety disorders, including obsessive-compulsive disorder, post
      traumatic stress disorder, and generalized anxiety disorder. Thus, atypical
      antipsychotics represent an important therapeutic option for the treatment of
      bipolar disorder, providing improvements in manic, depressive, and anxiety
      symptoms.

PMID- 14700011
TI  - Enhancing outcomes in the management of treatment resistant depression: a focus
      on atypical antipsychotics.
AB  - Clinical trials indicate that over 50% of depressed patients show an inadequate
      response to antidepressant therapy, and that incomplete recovery from major
      depressive disorder (MDD) increases the risk of chronicity and recurrence.
      Recovery, complete remission of symptoms, and a return to baseline psychosocial
      function, should be the goal of therapy. Poor response to adequate antidepressant
      treatment has been termed treatment resistant depression (TRD). Issues such as
      adherence, missed diagnosis of psychotic depression, bipolar disorder, or
      comorbid anxiety must be investigated as reasons why patients have not responded
      to initial therapeutic strategies. Beyond ensuring optimal use of the index
      antidepressant, treatment strategies for TRD include switching to another
      antidepressant, and augmentation or combination with two or more agents. Since
      little comparative data exist it is important to consider side-effect burden,
      partial response, and previous medication history when deciding between
      strategies. In patients with TRD, adding or augmenting with lithium, tri
      iodothyronine or atypical antipsychotics have demonstrated benefits. Augmentation
      with atypical antipsychotics, including risperidone, olanzapine, ziprasidone, and
      quetiapine, show promising results in terms of improving remission rates. Other
      interventions, including non-pharmacologic strategies and investigational
      physical treatments, have demonstrated some benefits, but availability and
      patient preference should also be considered. With today's therapeutic
      alternatives, full remission of depression is an attainable goal. For some
      patients, combination and augmentation strategies earlier in treatment may
      increase the likelihood of remission.

PMID- 14700012
TI  - Atypical antipsychotics and suicide in mood and anxiety disorders.
AB  - Globally, a million people commit suicide every year, and 10-20 million attempt
      it. Mood disorders, especially major depressive disorder (MDD) and bipolar
      disorder, are the most common psychiatric conditions associated with suicide.
      Primary (psychiatric and physical illness), secondary (psychosocial), and
      tertiary (demographic) risk factors for suicide have been identified. Comorbid
      psychiatric illness, particularly anxiety symptoms or disorders, significantly
      increase the risk of suicidal behavior. Current standard risk assessments and
      precautions may be of limited value, while assessing the severity of anxiety and
      agitation may be more effective in identifying patients at risk. Lithium is the
      medication that has most consistently demonstrated an antisuicidal effect. The
      effects of antidepressants and conventional antipsychotics on suicide risk are
      uncertain, but atypical antipsychotics appear promising. Atypical antipsychotics
      have beneficial effects on depressed mood both in patients with MDD and in
      patients with bipolar disorder. In addition, data in patients with schizophrenia
      have demonstrated a significant improvement in the incidence of suicidal behavior
      with clozapine compared with olanzapine. Electroconvulsive therapy appears to
      have an acute benefit on suicidality.

PMID- 14700013
TI  - Cognitive effects of atypical antipsychotics: focus on bipolar spectrum
      disorders.
AB  - Studies examining cognitive dysfunction in bipolar disorder have documented
      neuropsychologic impairment in some patients. Recollection memory, attention, and
      visual information processing may be particularly impaired in patients with
      bipolar illness. Cognitive impairment appears to worsen with illness progression,
      and may have a significant impact on function. Pharmacotherapy to treat bipolar
      disorder including lithium, anticonvulsants, antidepressants, and atypical
      antipsychotics may have varying effects on cognitive functioning. Treatment with
      atypical antipsychotics has been associated with improvement in various cognitive
      measures in patients with schizophrenia, and the little data available in
      patients with bipolar disorder suggest the potential for similar benefits.
      Studies to determine if current treatments for bipolar disorder can prevent,
      delay, or even improve cognitive dysfunction are needed.

PMID- 14700014
TI  - Clinical ethics case consultation.

PMID- 14700015
TI  - Safety and tolerability of atypical antipsychotics in patients with bipolar
      disorder: prevalence, monitoring and management.
AB  - Atypical antipsychotics are associated with fewer movement disorders and a lower
      risk of tardive dyskinesia than conventional antipsychotics, but are not without
      side-effects. Metabolic side-effects associated with some of the atypical
      antipsychotics are a concern for both clinicians and patients. Adverse events
      related to central nervous system effects, weight gain, and alterations in
      glucose, lipid, and prolactin levels in patients with depression, bipolar, and
      anxiety disorders have been reported. Balancing the significant benefits of
      treatment with these agents against the potential risks of metabolic disturbances
      and other adverse effects is crucial. Emerging data are making it possible to
      determine the risk-benefit analysis for specific atypical antipsychotics in
      individual patients and allow for targeted selection of treatment. A new concept
      of effectiveness is emerging that attempts to balance adverse effects of
      treatment with patient quality of life. Patients treated with atypical
      antipsychotics should have their weight, waist circumference, glucose, and lipids
      monitored on a regular basis. Monitoring of prolactin levels is not suggested;
      however, a baseline measurement before initiating treatment can be useful, with
      subsequent assessment only if a patient demonstrates symptoms. Prevention of
      weight gain is important. Diet and exercise should be considered for prevention
      and management, with the use of pharmacologic strategies approached with caution
      in patients with mood disorders. If a patient is at high risk of developing
      diabetes, certain pharmacologic agents have been shown to delay the onset of
      overt diabetes. Once diabetes or dyslipidemia are diagnosed, management should
      proceed in accordance with approved guidelines for these conditions.

PMID- 14700016
TI  - The advance directive: an expression of autonomy, but also of care.

PMID- 14700017
TI  - Targeted psychosocial interventions for bipolar disorder.
AB  - Pharmacotherapy is the foundation of treatment for bipolar disorder, but research
      suggests that adjunctive psychosocial interventions that are manualized,
      reproducible, time-limited, empirically supported, and strategically target a
      number of critical domains, can efficiently provide additional benefits.
      Psychoeducation as an adjunct of pharmacotherapy may be beneficial, but questions
      remain about the utility of this treatment for patients who are already compliant
      with medication treatment. Family educational interventions have demonstrated
      encouraging results in relapse prevention, but follow-up data are limited and
      application to patients who have limited social networks may be problematic.
      Reports on interpersonal and social rhythm therapy in patients with bipolar
      disorder are scarce, and what is available shows no differential effect on time
      to remission or relapse, but a significant impact on subsyndromal symptoms.
      Follow-up data suggest that patients receiving cognitive behavior therapy have
      significantly fewer bipolar episodes, shorter episodes, fewer hospitalizations,
      and less subsyndromal mood symptoms. It is unclear, however, if cognitive
      behavior therapy is superior to other active psychosocial treatments and whether
      its mechanism in patients with bipolar disorder is through changing dysfunctional
      cognitions or simply enhancing early symptom detection. Psychotherapies should be
      considered early in the course of illness to improve medication compliance and to
      help patients identify prodromes of relapse in order to take steps for
      prevention. In addition, some strategies may have a beneficial effect on residual
      symptoms, particularly symptoms of depression, and thus help move patients toward
      a more comprehensive functional recovery.

PMID- 14700018
TI  - 'Euthanasia' in the Third Reich: lessons for today?

PMID- 14700019
TI  - Suicide, physician-assisted suicide and euthanasia in men versus women around the
      world: the degree of physician control.

PMID- 14700020
TI  - Autonomy, gender, and preference for paternalistic or informative physicians: a
      study of the doctor-patient relation.

PMID- 14700021
TI  - Clinical ethics case consultation.
AB  - QUESTION: Nurses in the Pediatric ICU requested an ethics consultation asking "Is
      it fair to this child to continue painful experimental surgical procedures?"

PMID- 14700023
TI  - The institutional review board: a critical revisit to the protection of human
      subjects.

PMID- 14700024
TI  - Norwalk virus: a need for more awareness.

PMID- 14700025
TI  - Affective and evaluative descriptors of pain in the McGill pain questionnaire:
      reduction and reorganization.
AB  - Recent reports indicate that several descriptors of pain sensations in the McGill
      Pain Questionnaire (MPQ) are difficult to classify within MPQ sensory
      subcategories because of incomprehension, underuse, or ambiguity of usage.
      Adopting the same methodology of recent studies, the rule revealed that only 6 to
      18 words met criteria for the affective category and 5 of 11 words met criteria
      for the evaluative category, thus warranting a reduced list of words in these
      categories. This classification, the intensity ratings of the retained words
      correlated very highly with those originally reported for the MPQ. In conclusion,
      although the intensity ratings of MPQ affective and evaluative descriptors need
      no revision, selective reduction and reorganization of these descriptors can
      enhance the efficiency of this approach to pain assessment.

PMID- 14700026
TI  - Revisiting reproductive technology's slippery slope in the light of the concepts
      of Imago Dei, co-creation, and stewardship.

PMID- 14700027
TI  - Why not give Hippocrates a place at the table?

PMID- 14700028
TI  - Views of humanity and nursing practice: an analysis of nursing.

PMID- 14700029
TI  - Breakthrough of the year. The runners-up.

PMID- 14700030
TI  - Ways of approaching nursing ethics: some comparisons and contrasts.

PMID- 14700031
TI  - Practice guidelines should be endorsed.

PMID- 14700032
TI  - Practice guidelines should be endorsed.

PMID- 14700033
TI  - Hurtling toward eugenics...again.

PMID- 14700034
TI  - There needs to be equity within teams.

PMID- 14700035
TI  - The oral contraceptive pill and the principle of double effect.

PMID- 14700036
TI  - A defense of the neglected rhetorical strategy (NRS).

PMID- 14700037
TI  - Cardiac coping style, heartbeat detection, and the interpretation of cardiac
      events.
AB  - OBJECTIVES: Vigilance to, and avoidance of, cardiac sensations and symptoms were
      explored in three studies. DESIGN AND METHODS: In the first study, a self-report
      measure of cardiac vigilance and cardiac avoidance, the Cardiac Coping Inventory
      (CCI), was administered to 453 students, and its factor structure, internal
      consistency, and test-retest reliability were established. In the second, 31
      undergraduates completed the CCI, and their cardioceptive sensitivity was
      measured on a heartbeat detection task. In a third study of 91 patients with
      suspected myocardial infarction, the role of coping styles in symptom
      interpretations was analysed. RESULTS: Cardiac avoidance and vigilance were
      independent of general symptom reporting tendencies. Cardiac vigilance was
      negatively correlated with heartbeat detection. Among the patients, delay in
      seeking treatment was predicted by the perceived importance of chest pain, which
      was influenced by the intensity of chest pain and cardiac vigilance. CONCLUSIONS:
      Although individuals high in cardiac vigilance do not seem to be good detectors
      of their heartbeats in the laboratory, they appear to attach importance to heart
      symptoms in real life, resulting in a health-protective behaviour.

PMID- 14700038
TI  - Clinical ethics case consultation.
AB  - QUESTION: Should we seek a court order to use blood products and/or extra
      corporeal membrane oxygenation (ECMO) on this critically ill child of Jehovah's
      Witness parents?

PMID- 14700039
TI  - Thinking twice: cloning and in vitro fertilization.

PMID- 14700040
TI  - Evangelical engagements with eugenics, 1900-1940.

PMID- 14700041
TI  - Ethical considerations concerning South Africa's approval of a blood substitute.

PMID- 14700042
TI  - Alone no more: pain in premature children.
AB  - It is only recently that newborns have been recognised to feel pain. To avoid the
      drawbacks of common analgesics, alternative analgesic methods (e.g. sucking
      and/or oral sugar) have been proposed. We showed that these methods are of little
      effect without the relaxing, distracting, comforting presence of a person at the
      cribside who talks to and massages the baby. This is a further demonstration that
      newborns, including premature babies, look for a reassuring presence when
      experiencing pain. This is surprising as premature babies are relatively
      unreactive, often completely isolated in an incubator and considered incapable of
      social behavior. To the attentive observer, however, they reveal an unsuspected
      emotional world. Not only do they feel pain, but they are also capable of
      suffering, distress, anxiety and fear. This needs to be considered in neonatal
      analgesic treatment, even for extremely premature children. It is mandatory for
      caregivers to be a reassuring presence during painful procedures: premature
      babies are exacting patients. They not only feel pain, they even suffer; they
      request not only drugs, but a human presence nearby.

PMID- 14700043
TI  - The conception view of personhood: a review.

PMID- 14700044
TI  - The fiduciary covenantal relationship: a model for physician-patient
      relationships.

PMID- 14700045
TI  - Notice of duplicate publication.

PMID- 14700046
TI  - Your diagnosis, please. Neonate with hydrocephalus.

PMID- 14700047
TI  - Curing, caring and beyond: reflections for a clinical ethic.

PMID- 14700048
TI  - Xenotransplantation: animal rights and human wrongs.
AB  - The first successful human-to-human organ transplant was performed in 1954 when a
      kidney was transferred between two identical twins. In the years since this
      groundbreaking operation improvements in transplant surgery and an increasing
      ability to control organ rejection using imunosupressive medication has made
      transplantation the treatment of choice for a new generation. Unfortunately,
      these advancements have resulted in transplantation becoming a victim of its own
      success, as waiting lists have increased along with the waiting time for donor
      organs. For these reasons the use of animal organs for human transplantation is
      seriously being considered. Two groups of animals have been considered as donors:
      non-human primates and large non-primates such as pigs. Whilst many researchers
      in this field are very optimistic about the future, many opponents are concerned
      about the effects on public health and the environment. The primary barrier to
      transplantation is immunological rejection. With xenotransplantation an
      additional mechanism of rejection called hyperacute rejection occurs.
      Immunosuppressive drugs cannot control hyperacute rejection. For this reason, the
      majority of xenotransplantation trials attempted to date in humans have used
      chimpanzee or baboon organs. However, the problem will occur with
      xenotransplantation into humans of organs from more distantly related species
      such a pigs. This article highlights the ethical issues associated with the use
      of animal organs, and the impact of xenotransplantation on animal communities.

PMID- 14700049
TI  - Some Christian responses to the genetic revolution.

PMID- 14700050
TI  - Twigs of Terebinth: the ethical origins of the hospital in Judeo-Christian
      tradition.

PMID- 14700051
TI  - The ethics of advertising strategies in the pharmaceutical industry.

PMID- 14700052
TI  - Poliomyelitis vaccination campaign to recommence in Nigeria.

PMID- 14700053
TI  - Post-polio syndrome recognised by European parliament.

PMID- 14700054
TI  - Antiprogesterone hope for inherited neuropathy.

PMID- 14700055
TI  - NSAIDS and Alzheimer's disease: it's only Rock and Rho.

PMID- 14700056
TI  - Naturally occurring amino acid causes neurodegeneration.

PMID- 14700057
TI  - First disease model created by RNA interference.

PMID- 14700058
TI  - Copper may have a positive effect on Alzheimer's disease.

PMID- 14700059
TI  - Prion protein found outside the CNS.

PMID- 14700060
TI  - Names of viruses and virus species - an editorial note.

PMID- 14700061
TI  - Back to Latin tradition: a proposal for an official nomenclature of virus
      species.

PMID- 14700062
TI  - International naming of viruses - a digest of recent developments.

PMID- 14700063
TI  - Cardiotoxicity associated with intentional Ziprasidone and bupropion overdose.

PMID- 14700064
TI  - Ethiopia faces severe malaria epidemic. WHO predicts 15 million people could be
      infected.

PMID- 14700065
TI  - Health-care divide widens in North Korea. Rising prices and falling wages have
      left many urban workers reliant on international aid.

PMID- 14700066
TI  - GSK and Boehringer agree to generic AIDS drugs deal.

PMID- 14700067
TI  - Influenza vaccine shortage hits the USA.

PMID- 14700068
TI  - EU rushes through reduced cell and tissues legislation.

PMID- 14700069
TI  - NIH told to provide records in conflict of interest probe.

PMID- 14700070
TI  - Italy approves controversial legislation on fertility treatment.

PMID- 14700071
TI  - Fears grow for Brazil's youth. Increased life-expectancy estimates mask deep
      rooted problems with health care.

PMID- 14700072
TI  - Hospitals want to be heard in GPO debate.

PMID- 14700073
TI  - Fewer EDs, fewer poor at specialty facilities.

PMID- 14700074
TI  - Detection of characteristic signals from as-doped (<1 at.%) regions of silicon by
      transmission electron microscopy and convergent-beam electron diffraction.
AB  - Characteristic signals were detected from As-doped (< 1 at.%) regions of silicon
      by dark-field transmission electron microscopy and convergent-beam electron
      diffraction. A slight intensity increase was observed in 220 dark-field images,
      which may be explained by an increase of scattering amplitude due to the As
      doping. The doped region showed a much higher intensity in 004 dark-field images.
      The characteristic high intensity was observed for specimens with As
      concentrations of about 0.09-0.8 at.%. Convergent-beam electron diffraction
      patterns obtained from the As-doped region showed a characteristic rocking curve
      for 004 reflection. These characteristics should originate from incoherent
      elastically scattered electrons due to a static lattice distortion around the
      doped As atoms. The observed characteristics in dark-field images and rocking
      curves of the 004 reflection should be a good probe not only for investigating
      the concentration of doped atoms in Si lattice, but also for the amount of
      impurity and/or point defects in other crystalline materials.

PMID- 14700075
TI  - Nano-scale phase transformation in Ti-implanted austenitic 301 stainless steel.
AB  - Phase-transformation behaviours were investigated for austenitic 301 stainless
      steel during implantation at room temperature with 300 keV Ti ions to fluences of
      8 x 10(19) to approximately 3 x 10(21) ions m(-2) by means of transmission
      electron microscopy. The cross-sectional specimen was prepared using a focused
      ion beam. Plan observation of the implanted specimen showed that phase
      transformation from gamma-phase to alpha-phase was induced by implantation to a
      fluence of 3 x 10(20) Ti ions m(-2). The nucleation of the irradiation
      (implantation)-induced phase increased with the increase of the dose. The
      orientation relationship between the gamma matrix and the induced alpha
      martensitic phase was identified as (011)alpha//(111)gamma and [11-1]alpha//[10
      1], close to the Kurdjumov-Sachs relationship. Cross-sectional observation after
      implantation to a fluence of 5 x 10(20) ions m(-2) showed that phase
      transformation mostly nucleated near the surface and occurred in the higher the
      concentration gradient of the implanted ion, i.e. a higher stress concentration
      takes place and this stress introduced by the implanted ions acts as a driving
      force for the transformation.

PMID- 14700076
TI  - Quantitative analysis of static capacitance contrast in scanning electron
      microscopy.
AB  - A one-dimensional model is proposed for analysing static capacitance contrast
      (SCC) in scanning electron microscopy. For the large-scale integrated specimen
      covered by an insulating thin film, the imaging signal is calculated considering
      the redistribution of secondary electrons (SEs) and the charging process of the
      equivalent effective capacitance between the irradiation point and substrate. The
      calculated SCC as a function of the irradiation charge density is in good
      agreement with the experimental SCC. It is confirmed that the SCC arises from the
      redistribution of SEs and the difference in the effective capacitance of
      irradiation points under the condition of positive charging.

PMID- 14700077
TI  - Interface observation in Au/Ni/p-GaN studied by HREM and energy-filtering TEM.
AB  - The contact resistance of Au/Ni/p-GaN ohmic contacts for different annealing
      conditions was measured. This was then correlated with microstructure, including
      phase distribution, observed by high-resolution electron microscopy combined with
      energy-filtering imaging. A contact resistance of 2.22 x 10(-4) ohms cm2 for
      Au/Ni contacts to p-GaN after annealing at 500 degrees C for 5 min in air ambient
      was obtained. NiO layers were identified at the interface and upper area of
      annealed Ni/Au/p-GaN for air ambient. In addition, an Au layer was found at the
      interface of p-GaN due to a reversal reaction during annealing. Identification of
      the observed phases is discussed, along with possible formation mechanisms for
      the ohmic contacts in the Au/Ni/p-GaN system.

PMID- 14700078
TI  - Effect of surface lipopolysaccharide on the nature of membrane vesicles liberated
      from the Gram-negative bacterium Pseudomonas aeruginosa.
AB  - Membrane vesicles (MVs) were isolated from three isogenic lipopolysaccharide
      (LPS) mutants derived from the Gram-negative bacterium Pseudomonas aeruginosa
      PAO1 and compared with the parent strain. Parent cells possessed serotype 05
      (A+B+) LPS whereas the three mutants contained A+B-, A-B+ and A-B-. The MVs from
      the mutants contained their expected phenotypic LPS and varied in size,
      especially A-B- MVs. Mass and total protein differences were also noted. When the
      parent and mutant cells were treated with the outer membrane-perturbing
      antibiotic gentamicin, all cells produced 3-5 times more MVs and these had great
      variation in size, mass and total protein. It is concluded that the type of
      cellular LPS affects both the natural and gentamicin-induced development of MVs.

PMID- 14700079
TI  - Remineralization effects of xylitol on demineralized enamel.
AB  - We morphologically determined the effects of xylitol on the remineralization of
      artificially demineralized enamel. The samples were demineralized and then
      immersed in a remineralizing solution with or without 20% xylitol at 37 degrees C
      for 2 weeks. Samples were observed using contact microradiography, a multipurpose
      image processor (MIP) and a high-resolution electron microscope (HRTEM). Contact
      microradiography indicated that remineralization occurred in the surface and deep
      layers of samples immersed in a non-xylitol solution. Samples immersed in a
      xylitol solution demonstrated less mineralization in the outer 10 microm of the
      outermost surface layers, but more mineralization in the middle and deep layers,
      than was observed in the non-xylitol samples. The MIP evaluation indicated that
      remineralization was more prominent in layers at depths of 50-60 microm in the
      xylitol samples than in the non-xylitol samples. Observation of the xylitol
      samples by HRTEM revealed crystals of various sizes and irregular shapes with
      unclear crystal angles in the outermost surface layers. In the middle layers,
      they had thickened and angles of crystals are clear. These results indicate that
      xylitol can induce remineralization of deeper layers of demineralized enamel by
      facilitating Ca2+ movement and accessibility.

PMID- 14700080
TI  - SEM observation of the insect prepared by microwave irradiation.
AB  - The ptilinum of the fly and the compound eye are among the most fragile organs
      encountered during conventional procedures of morphological sample fixation. In
      order to identify a fixative suitable for preparing such samples for scanning
      electron microscopy, we examined various fixation conditions using microwave
      irradiation (MWI). The conditions examined were: (i) fixatives; (ii) temperature;
      (iii) concentration; (iv) duration; (v) dehydration; and (vi) substitution. The
      identified optimal conditions were 5% glutaraldehyde with MWI (350 W, 5 min). The
      MWI was continued until the maximal temperature of 75 degrees C was attained,
      followed by intermittent irradiation to maintain a temperature of 75 degrees C.
      After irradiation, the sample was left at room temperature for 24 h in the
      fixative and then dehydrated in increasing concentrations of ethanol. Each step
      in the ethanol series lasted for 24 h. The final absolute ethanol step included
      three solution changes, with each incubation lasting 1 h. A subsequent stepwise
      substitution of t-butyl alcohol for ethanol was conducted by reducing the ratio
      of 100% ethanol to t-butyl alcohol from 2:1 to 1:1 and then 1:2 (24 h each). The
      substitution was completed by three solution changes using 100% t-butyl alcohol,
      30 min each. The best results were obtained by freeze-drying samples using t
      butyl alcohol. The use of MWI improved fixative permeation, which occurred at a
      uniform rate throughout the sample. Comparison with temperature in a water bath
      at 75 degrees C indicated that the fixation effect of MWI was due to its heat
      generation in addition to some unknown mechanism.

PMID- 14700081
TI  - Entry of Bombyx mori cypovirus 1 into midgut cells in vivo.
AB  - In vivo entry of Bombyx mori cypovirus 1 into the silkworm midgut was studied by
      electron microscopy of ultrathin sections of midguts from silkworm larvae that
      had been administered virus-contaminated leaves. In 3 h, virions were observed
      outside and inside midgut cells, including columnar cells, goblet cells and
      muscle cells. Virions were seen adhering to the plasma membrane of microvilli,
      embedding in the membrane and settling themselves intact inside the microvilli of
      the columnar cells. These results suggested that intact virions entered columnar
      cells by means of direct penetration through the cell membrane. In 12, 24 and 48
      h, virogenic stromata and progeny virions were observed in columnar cells, but
      not in other midgut cells.

PMID- 14700082
TI  - The place of qualitative research in public health dentistry.

PMID- 14700083
TI  - Is depressive symptomatology associated with worse oral functioning and well
      being among older adults?
AB  - OBJECTIVES: Although depression negatively affects individuals' physical
      functioning and well-being, its association with oral functioning and well-being
      has not been examined previously. The objective of this study was to examine the
      association between depressive symptomatology and oral quality of life. METHODS:
      We utilized data from two samples of older adults: community-dwelling
      participants who used community primary care physicians in Los Angeles (n=1,653)
      and individuals who sought ambulatory care through four Department of Veterans
      Affairs facilities in the Boston metropolitan area (n=212). Depressive
      symptomatology was measured with the CES-D scale; Oral Quality of Life was
      measured with the Geriatric Oral Health Assessment Instrument and the Oral Health
      related Quality of Life measure. We conducted hierarchical regression analyses to
      examine the effects of depression on oral quality of life, controlling for self
      reported oral health, age, education, income, and marital status. RESULTS:
      Individuals with more depressive symptoms reported worse oral quality of life,
      controlling for sociodemographic factors and self-reported oral health. This
      finding persisted across multiple samples and both sexes, and using two measures
      of oral quality of life. CONCLUSION: These findings further emphasize the
      importance of treating depression among older adults, and suggest that both
      dentists and physicians have a role in recognizing and referring patients for
      such treatment.

PMID- 14700084
TI  - Developing short-form measures of oral health-related quality of life.
AB  - OBJECTIVES: Using the item-impact method, we developed an alternative short-form
      Oral Health Impact Profile (OHIP) that has good psychometric properties and
      minimal floor effects. METHODS: OHIP data were collected from a sample of older
      Canadians at two points in time. Data from the first administration were used to
      develop a 14-item short-form measure; data from the second compare the latter's
      psychometric properties with those of the original short form developed by Slade
      (1997), who used a controlled regression procedure. RESULTS: The short form based
      on the item-impact method had only two items in common with the short form
      derived from the regression approach and contained more high-prevalence items.
      The regression short form was subject to marked floor effects, while the impact
      short form had floor effects comparable to those of the full 49-item OHIP. The
      former discriminated between dentate and edentulous subjects, while the latter
      did not. Both discriminated between dentate subjects who did and did not wear
      dentures, those with and without dry mouth, and those with and without chewing
      problems. Both were also significantly associated with self-ratings of oral
      health, satisfaction with oral health, and self-perceived need for dental
      treatment. The strength of the associations was somewhat stronger with the
      regression short form, indicating that it performed better as a discriminatory
      instrument. However, because of its floor effects, it was markedly less sensitive
      to change than the impact short form. There was an indication that item-impact
      methods of shortening oral health-related quality of life measures produced more
      stable results across samples than the statistical approach. CONCLUSIONS: Because
      the content validity of short-form measures is always compromised, different
      short forms are required for different purposes and different patient
      populations. The regression short form developed by Slade (1997) is likely to be
      better when the aim is to discriminate, while the impact short form developed
      here may be preferable when the aim is to describe the oral health-related
      quality of life of populations or to detect change.

PMID- 14700085
TI  - Determinants of dropout in a community intervention trial on the caries
      preventive effect of chewing gums.
AB  - OBJECTIVES: This study describes determinants of dropout in a three-year
      community intervention trial of the effects of sugar-substituted chewing gums on
      caries progression rates. METHODS: A total of 602 children aged 9-14 years from
      28 school classes in five secondary schools in Kaunas, Lithuania, were given a
      clinical and radiographic baseline caries examination. The schools were assigned
      randomly to one of the following interventions: sorbitol/carbamide gum, sorbitol
      gum, xylitol gum, placebo gum, or no gum. Children in the four intervention
      schools were asked to chew at least five pieces of chewing gum per day,
      preferably after meals. The children were reexamined clinically after one, two,
      and three years of study, and radiographically after three years. RESULTS: A
      total of 33 children (6%) had dropped out before the one-year clinical
      examination, an additional 29 children (5%) dropped out before the two-year
      examination, and a further 108 children (18%) dropped out before the final three
      year clinical examination. A total of 230 children (39%) were not available or
      refused to participate in the three-year radiographic examination. Analyses using
      random effect logit models showed that, irrespective of time of follow-up, most
      of the cluster variation in dropout was related to school classes within the
      primary randomization units, the schools. The most important predictors of
      individual dropout were age and baseline caries experience, whereas sex was not
      associated with dropout. CONCLUSIONS: The results show that a community
      intervention trial of chewing gums carried out among schoolchildren is subject to
      cluster effects. Dropout was not primarily related to the randomization units
      themselves, i.e. the schools, but rather to subclusters of classes within the
      schools. These findings should be considered when designing community
      intervention trials and practical preventive programs among schoolchildren.

PMID- 14700086
TI  - A scoring system for the early detection of oral submucous fibrosis based on a
      self-administered questionnaire.
AB  - OBJECTIVES: The aims of the present study were to evaluate the frequent clinical
      complaints of oral submucous fibrosis (OSF) and to develop a scoring system for
      early detection of the disease by a self-administered questionnaire. METHODS: A
      total of 296 subjects were recruited, including 123 OSF patients without oral
      cancer and 173 betel quid chewers without OSF or oral cancer. A self-administered
      questionnaire was used to collect the symptom profile from study subjects. Their
      maximal mouth opening (MMO) between upper and lower incisor edges was measured
      and recorded by well-trained nurses. A binary logistic regression model examining
      the likelihood of OSF based on the eight symptoms of interest was used to develop
      the scoring system. RESULTS: Among 79 OSF subjects with an MMO < 35 mm, the most
      frequent complaint was trismus (87.3%), followed by burning sensation (76.0%) and
      xerostomia (72.2%). Among 44 OSF subjects with an MMO > or = 35 mm, burning
      sensation (68.2%) was the most frequent complaint, followed by trismus (54.5%)
      and xerostomia (54.5%). Six frequent complaints including trismus, burning
      sensation, xerostomia, sore throat, numbness, and oral ulceration were utilized
      to develop a scoring system for the early detection of OSF. The scoring system
      had an area under the receiver operating characteristic curve of 0.90.
      CONCLUSION: This study suggests a screening questionnaire of frequent complaints
      for the early detection of OSF.

PMID- 14700087
TI  - On adding a dental practice component to an ongoing longitudinal population-based
      study of oral health.
AB  - OBJECTIVE: To determine the feasibility and effectiveness of adding a dental
      practice component to the Florida Dental Care Study (FDCS). METHODS: The FDCS was
      a study of dental health in which no treatment was provided. In-person interviews
      and clinical examinations were conducted at baseline, 24 months, and 48 months,
      with six-month telephone interviews between those times. Participants reported
      any dentists visited and treatment received. All but four of the 764 participants
      at the 24-month session gave written permission to review their dental records.
      Dental hygienist research assistants abstracted information on treatment that was
      received during the 48-month interval. RESULTS: Of the 286 practices named by
      FDCS subjects, all but 10 (of whom five refused) practices participated. Eight
      practices allowed access to records, but did not allow us to record fees. Fees
      were unavailable at another 13 practices. Of the 764 persons who participated for
      the 24-month interview, 677 ultimately reported at least one dental visit during
      the first 48 months of the study. Of those 677, we located dental records on 619.
      We also found records on four of the 111 persons who reported no dental visits,
      by querying practices while recording information on other participants. Charts
      varied in comprehensiveness; nevertheless, in conjunction with office staff
      consultation, all practices had adequate record of what procedures were
      performed. CONCLUSIONS: Although time intensive, this method of collecting data
      substantially increased information about dental treatment received, compared to
      relying on participant self-report and clinical examination.

PMID- 14700088
TI  - Comparison of children's medical and dental insurance coverage by
      sociodemographic characteristics, United States, 1995.
AB  - BACKGROUND: Insurance coverage can reduce financial barriers that constitute a
      significant deterrent to obtaining medical and dental care, especially for
      children who reside in low-income households. We present baseline information on
      the codistribution of medical and dental coverage among US children according to
      sociodemographic characteristics before the enactment of the State Children's
      Health Insurance Program (SCHIP). METHODS: Data for 27,059 children 0-17 years
      old from the 1995 National Health Interview Survey (NHIS) were analyzed to
      examine the distribution of medical and dental insurance coverage by
      sociodemographic characteristics. Prevalence estimates and adjusted odds ratios
      with 95 percent confidence intervals were calculated using SUDAAN. RESULTS:
      Overall, 14.1 percent children were uninsured for medical care and 36.4 were
      uninsured for dental care; thus, there were 2.6 times as many children uninsured
      for dental than for medical care. Near-poor and Hispanic children were most
      likely to be without medical or dental coverage. Near-poor children were more
      likely to be uninsured for dental care than for medical care (43.8% vs 22.5%).
      CONCLUSION: Our findings, coupled with previous reports, suggest that the most
      serious problem concerning lack of dental insurance is among near-poor children.
      SCHIP has the potential to address dental coverage among near-poor children.

PMID- 14700090
TI  - Risk indicators for periodontal disease in a remote Canadian community--a dental
      practice-based study.
AB  - OBJECTIVES: The purpose of this cross-sectional study was to identify risk
      markers and risk indicators for periodontal attachment loss in a remote Canadian
      community. Of special interest was the association between smoking and
      periodontal disease experience. METHODS: Data were collected from a convenience
      sample of 187 adult patients attending a dental office in a rural community
      located in Northern Ontario. Information was obtained via a questionnaire and a
      periodontal examination. The questionnaire included the use of dental services,
      self-care behaviors, general health status, smoking, and personal
      characteristics. Periodontal health was assessed using the mean periodontal
      attachment loss (MPAL), measured at two sites on all remaining teeth and the
      proportions of sites examined with loss of 2 mm or more and 5 mm or more. Plaque
      scores and measures of the number of missing teeth also were obtained. The
      relationships between mean periodontal attachment loss, the proportion of sites
      with 5 mm or more of loss and independent variables such as age, sex, current
      smoking status, mean tooth plaque scores, flossing frequency, and regularity of
      preventive dental visits were examined in bivariate and multivariate analyses.
      RESULTS: The data revealed a mean periodontal attachment loss of 3.9 mm (SD=1.5).
      The mean proportion of sites examined with loss of 2 mm or more was 0.89 and the
      mean proportion with loss of 5 mm or more was 0.35. In linear regression
      analysis, plaque scores, the number of missing teeth, age, current smoking
      status, regularity of dental visits, and flossing frequency had statistically
      significant independent effects and explained 60.0 percent of the variance in
      mean periodontal attachment loss. Just over 30 percent of subjects had severe
      periodontal disease, defined as 50 percent or more of sites examined with loss of
      5 mm or more. In logistic regression analysis, missing teeth, dental visiting,
      smoking status, age, and flossing frequency had significant independent effects.
      The strongest association observed was with smoking, which had an odds ratio of
      6.3. The logistic regression model correctly predicted 64.3 percent of cases with
      severe disease. CONCLUSIONS: The data indicate that the periodontal health of
      these patients is poor. Risk indicators or markers of poor periodontal health in
      the population studied included missing teeth, plaque scores, age, current
      smoking status, regularity of dental visits, and flossing frequency. This
      supports previous findings that behavioral factors play an important role in
      periodontal disease.

PMID- 14700089
TI  - An ABCD program to increase access to dental care for children enrolled in
      Medicaid in a rural county.
AB  - OBJECTIVES: The Access to Baby and Child Dentistry (ABCD) Program addresses the
      needs of families in obtaining dental care. In this study, the program was
      evaluated in rural Stevens County, Washington. Aims were to assess utilization of
      dental services, average dental expenditures per child, and oral health status.
      METHODS: Medicaid-enrolled children aged 1-4 years were randomly assigned to the
      ABCD program (n=216) or to regular benefits (n=221). An outreach worker contacted
      each ABCD family and provided an orientation. Dental care utilization and
      expenditures were calculated from claims. A posttest-only design was used to
      evaluate oral health status. RESULTS: An enrollment effect was seen in ABCD, but
      the difference between groups was not sustained. There was a doubling of
      utilization between groups for the youngest cohort, while the others showed no
      differences. In the first year the rate was higher for the entire ABCD group than
      for the children not in ABCD (34.0% vs 24.7%). Thirty-three percent of ABCD
      children (70/212) who had visited the dentist had >1 appointment compared to 21.5
      percent (47/219) for the children not in ABCD who had visited the dentist. There
      was no overall difference in expenditures, while expenditures for preventive
      services were greater for ABCD. ABCD children had fewer teeth with initial
      caries. The average incremental cost per child per initial lesion prevented was
      31.44 dollars. CONCLUSION: ABCD most benefited the youngest cohort of children
      and improved health.

PMID- 14700091
TI  - Dental caries experience of female inmates.
AB  - OBJECTIVES: The purpose of this study was to determine the extent of dental
      caries and level of unmet dental need among female offenders in a federal prison
      in Connecticut. METHODS: All inmates admitted into the Federal Correctional
      Institution at Danbury, Connecticut, from May 31, 1997, to May 21, 1998, were
      given oral screening examinations (n=500; age range=20-65 years). The data were
      analyzed in terms of race/ethnicity and age groupings. DMF and D/DF scores were
      determined. RESULTS: The mean DMFT and DMFS scores were 16.8 and 57.0,
      respectively; the scores were higher for non-Hispanic whites and Hispanics than
      non-Hispanic blacks, and increased with age. The mean DT/DFT and DS/DFS scores
      were 36.8 percent and 36.0 percent, respectively. These scores were higher for
      non-Hispanic blacks than non-Hispanic whites and Hispanics, and decreased with
      age. CONCLUSIONS: Female prisoners had high levels of dental caries and racial
      disparities persisted in the prison.

PMID- 14700092
TI  - Distribution of axial, corneal, and combined ametropia in a refractive surgery
      unit.
AB  - PURPOSE: To group eyes in our refractive surgery unit on the basis of the origin
      of their ametropia and to assess the percentage of eyes in the different groups.
      METHODS: Refractive parameters and the axial eye length (AL) of 131 eyes of 131
      persons with different refraction were measured. The eyes were initially
      classified into five groups on the basis of the grade of their ametropia:
      hypermetropic (> +0.5 D, n = 35), emmetropic (between +/- 0.5 D, n = 24), low
      myopic (between -0.75 and -4.0 D, n = 24), medium myopic (between -4.25 and -8.0
      D, n = 24), and high myopic (over -8.0 D, n = 24). Then a classification scheme
      was made to group the origin of the ametropia on the basis of AL and corneal
      refractive power. RESULTS: In the hypermetropic group pure corneal origin was
      found in 8.6%, pure axial origin in 62.8%, and combined origin in 28.6% of the
      eyes. In the low myopic group these values were 20.9%, 29.2%, and 45.8%,
      respectively. In the medium and high myopic groups no pure corneal myopia was
      found, while axial myopia was found in 16.7% and combined myopia in 83.3% of the
      eyes. CONCLUSIONS: With the help of the classification scheme, an objective
      decision could be made as to whether the ametropia of a particular eye had axial,
      corneal, or mixed origin. The most interesting result was that in 83% of medium
      and high myopic eyes not only AL but also corneal refractive power contributed to
      the refractive error instead of the eyes being purely axially myopic.

PMID- 14700093
TI  - Improvement of human corneal endothelium in culture after prolonged hypothermic
      storage.
AB  - PURPOSE: To evaluate whether the organ culture method for human cornea
      preservation may be applied to corneas stored for several days at 4 degrees C.
      METHODS: The cell density, viability, and morphology of corneal endothelium were
      examined in 140 human corneas stored at 4 degrees C for the minimal time required
      for transport to the bank and for the preliminary controls of cornea status (1.6
      +/- 1.1 days) and in 46 corneas preserved at 4 degrees C for 6.1 +/- 1.9 days in
      Optisol-GS. The evaluation was repeated after 19.7 +/- 9.1 days of incubation at
      31 degrees C in a culture medium containing 2% newborn calf serum. RESULTS: After
      the hypothermic storage the corneal endothelium had a mean density of 2475 +/-
      159 cells/mm2 without significant difference between the short and the long-term
      incubation. Several corneas of the two groups showed signs of endothelium
      degeneration and were positive to trypan blue test. After the incubation at 31
      degrees C, the corneas with endothelial degeneration decreased by 52.2% and those
      positive to trypan blue decreased by 21.7%. Polymorphism (enlarged endothelial
      cells) increased from 9.6% to 14.5% of the corneas. The remodeling of the
      endothelium led to a 6.7% decrease in cell density. These results were similar
      after short-term and long-term storage at 4 degrees C. CONCLUSIONS: Organ culture
      was effective in improving corneal endothelium when the hypothermic storage was
      prolonged to the upper temporal limit for this procedure (7-10 days). These
      results may encourage the possibility of an eye bank to allocate the available
      cornea pool, thus decreasing the risk of discarding precious material.

PMID- 14700094
TI  - Analysis of autoantibody repertoires in sera of patients with glaucoma.
AB  - PURPOSE: Glaucoma is the second cause of blindness worldwide. It is usually
      considered a neurodegenerative disease. There is evidence that an autoimmune
      mechanism is involved in the development of glaucoma in some patients. The aim of
      this study was to analyze the IgG autoantibody repertoires in sera of glaucoma
      patients and healthy subjects. METHODS: A total of 82 patients were divided into
      four groups: healthy volunteers without any ocular disorders (CO, n = 30),
      patients with primary open-angle glaucoma (POAG, n = 19), ocular hypertension
      (OHT, n = 16), and normal tension glaucoma (NTG, n = 17). All groups were matched
      for age and gender. The sera of these patients were tested against Western blots
      of retinal antigens. Immunodetection was done using 4-chloro-1-naphthol staining.
      The autoantibody patterns were digitized and subsequently analyzed by
      multivariate statistical techniques. RESULTS: All patients showed different,
      complex staining patterns of autoantibodies against retinal antigens. There was
      an increase in the number of peaks in sera of patients with primary open-angle
      glaucoma (POAG) compared to healthy subjects (CO). Including all peaks the
      analysis of discriminance revealed a statistically significant difference between
      the patterns of POAG compared to all other groups (p < 0.01). Sera of normal
      tension glaucoma (NTG) had no statistically different autoantibody pattern
      compared to those of control subjects. CONCLUSIONS: In this study, we
      demonstrated a difference in the IgG autoantibody patterns of primary open-angle
      glaucoma patients compared to healthy subjects. However, the patterns were not
      significantly different in normal tension glaucoma compared to control subjects.

PMID- 14700095
TI  - In vitro analysis of AcrySof intraocular lens glistening.
AB  - PURPOSE: The authors studied the effects of changes in packaging solution
      temperature on the development of glistening in acrylic intraocular lenses
      (AcrySof, Alcon). METHODS: Glistening was examined by slit lamp at each
      condition. In Experiment 1, AcrySof lenses were soaked in physiologic saline
      adjusted to 15 degrees C and 37 degrees C in an incubator. In Experiment 2,
      AcrySof lenses were soaked in physiologic saline adjusted to 37 degrees C and 60
      degrees C for 5 min, then stored in physiologic saline adjusted to 15 degrees C.
      In Experiment 3, glistening formation was induced in AcrySof lenses by soaking
      them in warm water (37 degrees C). The lenses were allowed to dry at 15 degrees C
      and then soaked in physiologic saline adjusted to 15 degrees C. After storage of
      dry AcrySof lenses at 37 degrees C in an incubator for 10 months followed by
      soaking in physiologic saline adjusted to 15 degrees C, glistening formation was
      evaluated in Experiment 4. RESULTS: Glistening became observable after 1 month,
      despite the temperature having been lowered to 15 degrees C. No glistening was
      observed in the lenses soaked in physiologic saline adjusted to 37 degrees C
      after 5 min, but glistening was observed 1 month after soaking. When allowed to
      dry at 15 degrees C, the glistening decreased. After 1 month of soaking at 15
      degrees C, glistening was again observable. CONCLUSIONS: AcrySof lenses soaked in
      warm water for a short time may change characteristics, and therefore, close
      monitoring of the temperature and time of soaking is necessary to prevent
      glistening formation.

PMID- 14700096
TI  - Open-sky capsulorrhexis in triple procedure: with or without trypan blue?
AB  - PURPOSE: To establish the beneficial effects of trypan blue 0.1% capsule staining
      in open-sky capsulorrhexis during triple procedure. METHODS: Patients who
      underwent penetrating keratoplasty (PK) with phacoemulsification and intraocular
      lens (IOL) implantation were divided into two groups. Group 1 consisted of 31
      eyes of 26 patients with a mean age 64.4 +/- 6.9 years and anterior lens capsule
      was stained with trypan blue 0.1% to perform open-sky capsulorrhexis. In Group 2,
      capsulorhexis was performed without staining of the anterior capsule in 19 eyes
      of 17 patients with a mean age 60.6 +/- 5.3 years. The rates of complete
      capsulorrhexis and intra- and postoperative capsule-related complications were
      compared between the groups. RESULTS: The most common diagnosis before PK was
      corneal opacification in both groups. Open-sky capsulorrhexis was not completed
      in 3 eyes (9.6%) in Group 1 and in 9 eyes (47.3%) in Group 2. The rates of
      incomplete capsulorrhexis, posterior capsule tear, and transscleral fixation IOL
      implantation were higher in Group 2 (for each, p < 0.05). The diameters of
      capsulorrhexis were smaller than 4.5 mm in one eye in Group 1 and in two eyes in
      Group 2, and larger than 6.5 mm in two eyes in Group 1 and in three eyes in Group
      2. Malposition of IOL, zonular dialysis, retinal detachment, and pupil capture
      were only observed in eyes in Group 2. In the follow-up period, there were no
      adverse reactions due to application of trypan blue in Group 1. CONCLUSIONS:
      Trypan blue staining of the anterior capsule during triple procedure helps the
      surgeon perform open-sky capsulorrhexis more easily and safely and in proper
      dimensions, provides positive effects on the other steps of the surgery, and
      decreases the rate of posterior capsule tear formation.

PMID- 14700097
TI  - The effect of anterior chamber maintainer on anterior chamber contamination.
AB  - PURPOSE: To evaluate the effect of anterior chamber continuous infusion
      maintainer system on the contamination of anterior chamber in phacoemulsification
      surgery. METHODS: Clear corneal phacoemulsification surgery was performed in 132
      eyes of 132 randomly selected patients with cataract who were divided into two
      groups of 66 eyes according to the use of an anterior chamber maintainer (ACM)
      system. The fluid specimens were taken from anterior chamber in the beginning and
      at the end of the surgery. They were transferred under anaerobic conditions and
      investigated by culturing onto blood agar and thiogluconate broth media.
      Differences between the two groups with respect to contamination of the specimens
      were investigated. RESULTS: The mean age of the group undergoing surgery without
      a maintainer system (Group A) was 63 +/- 10 years (min = 41, max = 80) versus 59
      +/- 10 years (min = 33, max = 80) in the other group (Group B) in which the
      maintainer was used during surgery. In the postoperative specimen, Micrococcus
      species were isolated from one eye (1.5%) in Group A and S. pyogenes in one eye
      (1.5%) from Group B. Mean follow-up interval was 12 +/- 6 (min = 4, max = 28)
      months. CONCLUSIONS: The use of ACM system in clear corneal phacoemulsification
      surgery carries no additional risks as far as contamination is concerned.

PMID- 14700098
TI  - The effect of intraoperative antibiotics in irrigating solutions on aqueous humor
      contamination and endophthalmitis after phacoemulsification surgery.
AB  - PURPOSE: To determine the efficacy of intraoperative antibiotic use in irrigating
      solutions on aqueous humor contamination during phacoemulsification surgery and
      to evaluate the corresponding risk of postoperative endophthalmitis. METHODS: 644
      eyes of 640 patients who underwent phacoemulsification surgery with foldable
      intraocular lens (IOL) implantation were included in this study. Preoperative
      conjunctival smears were taken and eyes were allocated to receive irrigating
      infusion fluid containing either balanced salt solution (BSS)-only (group 1; 322
      eyes) or BSS with antibiotics (vancomycin and gentamycin) during surgery (group
      2; 322 eyes). Bacterial contamination rates of aqueous humor samples taken in the
      beginning and at the end of operation were compared. Predictive factors for the
      development of postoperative endophthalmitis were determined by clinical and
      microbiologic analyses. RESULTS: The rates of culture-positivity were similar
      between group 1 and group 2 for both preoperative conjunctival smears and aqueous
      samples (p > 0.05). Aqueous samples taken at the end of operation were found to
      be contaminated in 68 (21.1%) eyes in group 1 and 22 (6.8%) eyes in group 2, and
      the difference was significant (p = 0.0001; OR = 3.65 (2.1-6.0)). Capsular
      rupture was associated with higher rate of contamination in both groups (p =
      0.0001; OR = 7.7 and p = 0.0001; OR = 8.1). Two eyes in the BSS-only group
      developed postoperative endophthalmitis and these cases had posterior capsular
      rupture during the surgery and culture-positivity for staphylococcus epidermidis
      throughout the study. CONCLUSIONS: Intraoperative antibiotic irrigation decreases
      aqueous humor contamination during phacoemulsification. Further studies are
      warranted to determine the interrelationship between aqueous humor contamination
      and endophthalmitis in eyes with posterior capsular rupture.

PMID- 14700099
TI  - Malondialdehyde and antioxidant enzyme levels in the aqueous humor of rabbits in
      endotoxin-induced uveitis.
AB  - PURPOSE: To investigate the role of oxidative stress in endotoxin-induced
      uveitis. METHODS: Lipopolysaccharide was injected intravitreally into the right
      eyes of rabbits. Sterile saline was injected intravitreally into the left eyes as
      a control. Inflammation was assessed according to clinical score, aqueous humor
      cell count, and protein levels. Malondialdehyde, superoxide dismutase,
      glutathione peroxidase, catalase, and nitrite levels were measured in the aqueous
      humor. RESULTS: The clinical grade (p < 0.01), inflammatory cell count (p <
      0.001), and protein content (p < 0.001) were significantly higher in the aqueous
      humor of eyes with uveitis than in that of controls. Malondialdehyde (p < 0.01)
      and nitrite (p < 0.001) levels in the aqueous humor of eyes with uveitis were
      significantly higher than in the control group. Superoxide dismutase (p < 0.001),
      glutathione peroxidase (p < 0.001), and catalase (p < 0.001) levels were
      significantly lower in the aqueous humor of eyes with uveitis than in that of the
      controls. CONCLUSIONS: Oxygen free radicals may be implicated as a mediator of
      inflammation in endotoxin-induced uveitis. The increase in free radicals in the
      aqueous humor may play a role in the pathogenesis of endotoxin-induced uveitis.

PMID- 14700100
TI  - Retinopathy of prematurity: any difference in risk factors between a high and low
      risk population?
AB  - PURPOSE: To document incidence of and risk factors for development of retinopathy
      of prematurity (ROP) in a population of low birthweight infants (< 1500 g).
      METHODS: The authors registered clinical characteristics (birthweight,
      gestational age (GA), Clinical Risk Index for Babies (CRIB), Apgar score,
      respiratory characteristics (intubation, ventilation, respiratory support,
      supplemental oxygen, oxygenation index), prescription of dopamine, and maximal
      creatinemia) by retrospective chart review in two consecutive CRIB score-based (<
      851 g, 851-1350 g) categories. Chi square and Mann-Whitney U tests were used to
      compare clinical characteristics in both categories and a stepwise logistic
      regression was done to document independent risk factors for either stage 3 (<
      851 g) or any grade of ROP (851-1350 g). RESULTS: Incidence of ROP was 65/157
      (41%; 76% in < 851 g and 22% in 851-1350 g). Incidence of stage 3 ROP was 25/46
      (54%) in the < 851 g and 4/84 (5%) in the 851-1350 g group. Among other risk
      factors, maximal creatinemia was a risk factor in the 851-1350 g cohort (p <
      0.03). In a logistic regression model, only GA (OR 0.42) remained significant in
      the lowest birthweight category; in the 851-1350 g cohort, GA (OR 0.53) and CRIB
      score (OR 1.7) were independent risk factors for ROP. CONCLUSIONS: In relatively
      more mature infants (851-1350 g), the risk to develop ROP is based on GA and on
      neonatal severity of disease (CRIB score); in the tiniest infants, GA is the most
      important risk factor. Microangiopathy might explain the association of maximal
      creatinemia and the risk of developing ROP.

PMID- 14700101
TI  - Two-stage procedure for management of large exposure defects of hydroxyapatite
      orbital implant.
AB  - PURPOSE: To report the results of a newly devised two-stage surgical technique
      for management of large hydroxyapatite exposure defects. METHODS: Eight patients
      with exposed hydroxyapatite orbital implant were treated in two stages. The
      exposed hydroxyapatite anterior surface was burred down and the defect was
      directly closed 3 to 13 months after the primary procedure. Then a mucous
      membrane or dermis-fat graft was added for socket reconstruction. RESULTS: Trauma
      was the primary cause of enucleation in all patients. Hydroxyapatite exposures
      occurred 1 to 2 weeks after implantation. Mean defect size was 15 mm in the
      greatest dimension (range 10-21 mm). Socket reconstruction was done in seven
      patients with mucous membrane graft and in one patient with dermis fat graft 3 to
      13 months after direct repair of the defects. All eight patients maintained
      closure of the defects during a mean follow-up of 13 months (range 9-19 months).
      CONCLUSIONS: Management of hydroxyapatite exposures, especially those with large
      defects, can be difficult. Based on our experience, optimal results can be
      obtained after direct closure of the defect under minimal tension at the expense
      of foreshortening the fornices after which the socket can be reconstructed with a
      mucous membrane or dermis fat graft as a secondary procedure.

PMID- 14700103
TI  - Ocular complication of intralesional corticosteroid injection of a chalazion.
AB  - PURPOSE: To report a major complication of intralesional corticosteroid injection
      for the treatment of a chalazion. METHODS: A 28-year-old woman presented with a 4
      day history of decreased vision in her left eye that developed after
      corticosteroid injection to her upper eyelid for the treatment of chalazion. The
      visual acuity was 20/20 in her right and finger counting in her left eye.
      Anterior segment examination showed an inferior corneal opacity with positive
      Seidel test and cataract. RESULTS: A soft contact lens was applied to cornea and
      antibiotic therapy was given to prevent endophthalmitis. Cataract was removed by
      lens aspiration and a posterior chamber intraocular lens was implanted. After
      surgery, the visual acuity increased to 20/20 in her left eye. CONCLUSIONS:
      Inadvertent corneal penetration and traumatic cataract are possible and serious
      complications of intralesional corticosteroid injection.

PMID- 14700102
TI  - Intraocular pressure, quality of block, and degree of pain associated with
      ropivacaine in peribulbar block: a comparative randomized study with bupivacaine
      lidocaine mixture.
AB  - PURPOSE: To compare the effects of ropivacaine and bupivacaine-lidocaine
      combination on intraocular pressure, quality of block, and degree of
      postoperative pain in peribulbar block. METHODS: The study group involved 32
      patients undergoing elective cataract surgery under peribulbar block. Patients
      were divided into two groups according to the local anesthetic used: Group 1 (n =
      16), ropivacaine 0.75%; and Group 2 (n = 16), bupivacaine 0.5%-lidocaine 2%
      mixture. Intraocular pressure was measured at four time points: before block
      (control), 1 min after block, 5 min after block, and 15 min after block with
      Tonopen. Quality of block was evaluated using a three-point scoring system based
      on the reduction of globe motility. Patients were asked their degree of
      intraoperative pain by using a five-point verbal rating score after the surgery.
      RESULTS: Mean values of intraocular pressure after block were significantly lower
      in Group 1 in comparison to Group 2 (p < 0.05, Mann Whitney test). The quality of
      block was better in Group 2, and the degree of postoperative pain was lower in
      Group 1 (p < 0.05, Mann-Whitney test). CONCLUSIONS: Ropivacaine used in
      peribulbar block is better than bupivacaine-lidocaine mixture under the same
      standard conditions in terms of reducing intraocular pressure and postoperative
      pain in intraocular surgery.

PMID- 14700104
TI  - Endophthalmitis caused by Mycobacterium abscessus.
AB  - PURPOSE: To describe the clinical and laboratory features of a case of
      endophthalmitis caused by Mycobacterium abscessus in a patient immunocompetent.
      METHODS: case report. A 65-year-old woman with bilateral cataracts was treated by
      surgery with phacoemulsification and posterior chamber lens implantation.
      RESULTS: The funduscopic examination showed vitreous cells over the optic nerve
      head, chorioretinal infiltrates, and focal vasculitis. Vitreous humor aspirate
      disclosed acid-fast bacilli. In the culture on Lowenstein-Jensen medium grew
      colonies identified as M. abscessus. CONCLUSIONS: M. abscessus is cause of
      endophthalmitis and crystalline keratopathy. Risk factor include surgical
      intervention or exogenous contamination. Our patient has no systemic pathology
      predisposing to the development of endophthalmitis.

PMID- 14700105
TI  - Bilateral Parry-Romberg syndrome associated with retinal vasculitis.
AB  - PURPOSE: To describe an unusual case of bilateral progressive facial hemiatrophy
      (Parry-Romberg syndrome (PRS)) associated with retinal vasculitis. METHODS: In a
      37-year-old man with bilateral PRS, retinal vasculitis of the right eye was
      evident on fundus examination and fluorescein angiography. Right temporalis
      muscle biopsy and needle electromyography of the masseter muscles were performed.
      The patient underwent immunosuppressive therapy and retinal laser
      photocoagulation. RESULTS: Biopsy specimens showed large fibrosis with focal
      lymphohistiocytic infiltration of the muscle fibers. Electromyographic findings
      are consistent with a primary muscle disease. Visual acuity improved from 20/25
      to 20/20 in the right eye with a follow-up of one year. CONCLUSIONS: The evidence
      of retinal vasculitis and the histologic findings of facial changes observed in
      this PRS case could support the pathogenetic model of a chronic inflammatory
      process as a plausible explanation for progressive facial hemiatrophy.

PMID- 14700106
TI  - Retinal periphlebitis resembling frosted branch angiitis with nonperfused central
      retinal vein occlusion.
AB  - PURPOSE: To report the unusual association between severe retinal periphlebitis
      resembling frosted branch angiitis and nonperfused central retinal vein occlusion
      (CRVO). METHODS: Observational case reports. RESULTS: Patient 1 was a 28-year-old
      man who presented with extensive sheathing involving all retinal veins in one eye
      followed by nonperfused CRVO. Twenty-seven months after initial presentation, he
      developed perfused CRVO in the other eye followed by periphlebitis that
      progressed into nonperfused CRVO. Patient 2 was a 47-year-old man who presented
      with unilateral severe retinal periphlebitis associated with nonperfused CRVO.
      Despite systemic administration of corticosteroid therapy, rubeosis iridis
      developed in both patients and neovascular glaucoma developed in Patient 1
      despite full panretinal photocoagulation. Extensive systemic workup and
      coagulation studies were unremarkable except for the presence of antiphospholipid
      antibodies in both patients and elevated plasma homocysteine level in Patient 2.
      CONCLUSIONS: Severe retinal periphlebitis complicated by nonperfused CRVO is
      associated with poor visual outcome despite appropriate medical and surgical
      treatment.

PMID- 14700107
TI  - Clonazepam associated retinopathy.
AB  - PURPOSE: To report a case of retinopathy associated with the longterm intake of
      the antiepileptic drug clonazepam. METHODS: Case report. RESULTS: A 36-year-old
      woman, with a history of long-term use of the antiepileptic drug clonazepam
      developed subtle visual disturbances. Funduscopy revealed areas of mild
      depigmentation of the retinal pigment epithelium throughout the posterior pole
      bilaterally corresponding to transmission hyperfluorescence on fluorescein
      angiography. There was no history of any inherited retinal degenerative disease
      and no other known agent responsible for retinal toxicity had been used.
      CONCLUSIONS: The longstanding intake of the antiepileptic drug clonazepam may be
      associated with the development of toxic retinopathy.

PMID- 14700108
TI  - Acute commotio retinae determined by cross-sectional optical coherence
      tomography.
AB  - PURPOSE: To demonstrate the cross-sectional anatomy in acute commotio retinae.
      METHODS: A 27-year-old male with unilateral decreased vision after acute blunt
      ocular trauma, was examined by optical coherence tomography (OCT). RESULTS:
      Visual acuity was 20/20 OD and 20/50 OS. Fundus examination OS demonstrated a
      mild edema in the papillomacular and foveal area. OCT confirmed a separation of
      the neurosensory retina and the retinal pigment epithelium (RPE). The thickness
      of the retina was normal and the contour of the foveola intact. The uncommon
      hyperreflective band at the outer retina may present the traumatic disruption of
      photoreceptors. CONCLUSIONS: In vivo investigations by OCT confirmed previous
      histological studies, a commotio retinae consists a disruption and fragmentation
      at the level of the foveal photoreceptor segments and RPE.

PMID- 14700109
TI  - Hypo-estrogenemia in retinal vasculopathy due to primary antiphospholipid
      antibody syndrome.
AB  - PURPOSE: To report hypo-estrogenemic state in a case of recurrent vitreous
      hemorrhages due to primary antiphospholipid antibody syndrome. METHODS:
      Interventional case report. A 40-year-old woman presented with recurrent vitreous
      hemorrhages. Treated initially with laser photocoagulation followed by hormone
      replacement therapy. RESULTS: Cessation of vitreous hemorrhage since starting
      hormone replacement therapy (twenty months ago). CONCLUSIONS: This is the first
      documented case of hypo-estrogenemia in lupus anticoagulant retinopathy. The
      response of this condition to estrogen is worth exploring.

PMID- 14700110
TI  - Parasuicide and suicide in the south-west of Ireland.
AB  - BACKGROUND: Suicidal behaviour has become recognised as a major public health
      problem. AIM: To examine hospital-treated parasuicide and suicide in the Southern
      and Mid-Western Health Boards. METHODS: Parasuicide data were derived from
      independent data collection in general and psychiatric hospitals and prisons
      between 1995 and 1997. The corresponding suicide data were obtained
      electronically from the Central Statistics Office. RESULTS: Respectively, the
      annual person-based male, female and total European age-standardised rates were
      128.9, 154.3 and 141.3 per 100,000 for parasuicide compared to 22.7, 5.5 and 14.1
      per 100,000 for suicide. The parasuicide/suicide ratio varied markedly by age,
      gender, area and marital status. The majority of suicides were by hanging or
      drowning whereas drug overdose made up the vast majority of parasuicide acts.
      Parasuicide was largely a city phenomenon confined to the young of both genders
      whereas suicide was a significant problem for city and county men, especially
      young adult men. CONCLUSION: There are striking differences between the patterns
      of fatal and non-fatal suicidal behaviour in Ireland, which should be considered
      in prevention initiatives.

PMID- 14700111
TI  - A prospective, randomised trial of preoperative rectal diclofenac: are we closing
      the gate after the horse has gone?
AB  - BACKGROUND: Diclofenac sodium is a non-steroidal anti-inflammatory agent commonly
      used to provide analgesia post-surgery. It is common clinical practice to
      administer a diclofenac suppository at induction to contribute to pre-emptive
      analgesia (PEA). Diclofenac takes up to 30 minutes to attain maximal plasma level
      after rectal administration. AIM: To compare post-operative analgesia in patients
      who received diclofenac 30-45 minutes preoperatively, or at induction of
      anaesthesia. METHODS: A prospective, randomised, double-blind controlled trial in
      157 patients undergoing varicose vein surgery. Group A (control) received a
      rectal placebo 30-45 minutes preoperatively, group B received diclofenac 100 mg
      30-45 minutes preoperatively and group C received placebo 30-45 minutes
      preoperatively and diclofenac 100 mg at induction. Outcome measures were Visual
      Analogue Scores (VAS) and requirement for rescue analgesia. RESULTS: Patients in
      group A had significantly poorer analgesia than patients in groups B and C. There
      were no significant differences in VAS values and requirements for rescue
      analgesia between groups B and C 3-4 hours and 18-22 hours postoperatively.
      CONCLUSION: For patients undergoing varicose vein surgery preoperative
      administration of rectal diclofenac significantly improves post-operative
      analgesia and this effect is independent of whether it is given at induction or
      30-45 minutes preoperatively.

PMID- 14700112
TI  - Appropriateness of gastric antisecretory therapy in hospital practice.
AB  - BACKGROUND: Recent data indicate an exponential increase in proton pump inhibitor
      (PPI) prescribing, and concerns are raised regarding the appropriateness of these
      prescriptions and the financial implications. AIM: To survey the appropriateness
      of PPI prescription in a cohort of patients in a tertiary referral hospital.
      METHODS: Prescription records of all inpatients on a randomly selected day were
      reviewed. The appropriateness of prescription and relevant investigations were
      identified by interview of patients, review of patient records and of a
      computerised endoscopy records system. RESULTS: Thirty-two per cent (87 of 272)
      of all patients were on PPIs. A valid indication for therapy was not apparent in
      63% of the patients on PPIs with the only predictive factor for inappropriate
      prescription being increasing age. Only 36 of the 87 patients on PPIs had
      undergone appropriate investigations for their gastrointestinal symptoms. Gender,
      age, speciality of admission or duration of hospital stay did not influence the
      appropriateness of prescription or performance of relevant investigations.
      CONCLUSION: There appears to be a widespread and inappropriate use of PPIs in
      hospital practice.

PMID- 14700113
TI  - Folic acid knowledge and use among relatives in Irish families with neural tube
      defects: an intervention study.
AB  - BACKGROUND: Relatives in families where a child has a neural tube defect (NTD)
      may be at higher risk of having an affected child. Little is known of their level
      of knowledge and use of folic acid. AIM: To carry out an intervention study
      intended to increase knowledge and use of folic acid among relatives. METHODS:
      One hundred aunts and female first cousins (relatives of the proband) were
      interviewed by telephone before and after receiving an information pack. RESULTS:
      At baseline, although knowledge of the benefits of folic acid was high (73%), use
      of folic acid was low (8.8%). After the intervention, knowledge increased and use
      went up to 19% (p < 0.05). CONCLUSIONS: This study suggests that relatives in
      Irish NTD families have a high level of information about folic acid benefits.
      This awareness may not translate into action since the intervention produced only
      a modest increase in folic acid use overall. Future studies focussing on women
      who are planning a pregnancy may show larger benefits from intervention.

PMID- 14700114
TI  - Hepatitis C infection among drug users attending general practice.
AB  - BACKGROUND: The prevalence of hepatitis C (HCV) infection among injection drug
      users is high and addiction-related care is increasingly being provided by GPs in
      Ireland. AIMS: To determine the prevalence and associated factors of HCV
      infection among injecting drug users attending general practice. METHODS: The
      records of 571 patients attending 42 general practices in the Eastern Regional
      Health Authority (ERHA) area for methadone maintenance treatment were reviewed.
      RESULTS: The HCV status was recorded in 380 cases (67%). Of these, 193 had a test
      performed by their GP, 74 had been tested by another service and 113 had no
      evidence of being tested, but HCV status was recorded based on information
      provided by the patient himself. A total of 276 cases were identified as being
      HCV positive (prevalence 73%), with no difference in prevalence between the three
      sources of information (p = 0.12). A history of injecting drug use was the major
      determinant of testing for HCV. CONCLUSIONS: While a large proportion of drug
      users attending GPs for methadone maintenance treatment are known to be HCV
      positive, a considerable number have not been tested. Barriers to testing need to
      be explored to facilitate comprehensive screening.

PMID- 14700115
TI  - Timing of laparoscopic cholecystectomy in acute cholecystitis.
AB  - BACKGROUND: Laparoscopic cholecystectomy is associated with an increased
      conversion rate in acute cholecystitis. AIM: To review the operative management
      of symptomatic cholelithiasis with particular reference to conversion rates and
      morbidity for laparoscopic cholecystectomy for acute cholecystitis. METHODS:
      Patients undergoing cholecystectomy between January 1994 and December 1998 were
      recruited. Demographic details, diagnosis, duration of symptoms, treatment,
      outcome, post-operative stay and complications were recorded. RESULTS: Complete
      data were available on 482 patients (84%). Laparoscopic cholecystectomy was
      attempted in 120 of 132 patients (91%) with acute cholecystitis and 329 of 350
      patients (94%) with non-acute gallbladder disease. Conversion rates were 27%
      (33/120) and 6.7% (22/329) for acute and non-acute gallbladder disease,
      respectively (p < 0.001 chi2 test). Relating the interval from onset of symptoms
      to surgery, conversion rates for acute cholecystitis were: < 3 days, 5/17 (29%);
      4 to 42 days, 14/59 (23%) and > 42 days, 14/44 (31%). There were three bile duct
      injuries, two in the delayed (> 45 days) acute group and one in the non-acute
      group. CONCLUSION: Early laparoscopic cholecystectomy is the treatment of choice
      for acute cholecystitis, but is associated with a high conversion rate
      independent of the timing of surgery.

PMID- 14700116
TI  - D2 lymphadenectomy in the management of gastric cancer.
AB  - BACKGROUND: Gastric carcinoma is a significant cause of death in Ireland. Surgery
      offers the best option of cure, but the five-year survival following resection
      remains dismal at 10-15%. Experience from Japan and from some Western units
      suggest that an extended (D2) lymphadenectomy in association with gastrectomy
      increases the prospect of cure, but concern about the morbidity and mortality of
      this operation and lack of evidence from randomised studies has limited its
      acceptance. AIMS: This study reports the experience of a specialist upper
      gastrointestinal unit with D2 gastrectomy in a four-year audit. METHODS: Sixty
      two resections were performed for gastric cancer. RESULTS: Nineteen patients were
      deemed unsuitable for the D2 procedure and underwent a more limited
      lymphadenectomy (D0 or D1). Forty-three patients underwent D2 resection, 12 with
      an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total
      distal resection. Eight patients undergoing D2 resection had extended resections,
      five with splenectomy and three with a distal pancreatectomy. Post-operative
      complications occurred in 31% of patients. Thirty-day and 90-day mortality were
      zero. Median survival was 822 days in the D2 group (range 120-1,320).
      CONCLUSIONS: These results show that a D2 gastrectomy can be performed with a low
      morbidity and mortality and a median survival of greater than two years.

PMID- 14700117
TI  - A comparison of the functional durability of the AMS 800 artificial urinary
      sphincter between cases with and without an underlying neurogenic aetiology.
AB  - AIM: To compare the efficacy and functional durability of the American Medical
      Systems 800 (AMS 800) artificial urinary sphincter (AUS) device for patients with
      neurogenic and non-neurogenic incontinence. METHODS: From 1985 to 2000, 38
      patients underwent implantation of an AMS 800 AUS at our institution. Thirty of
      these patients had complete records and follow-up data available. The mean follow
      up for these two groups of patients was six years. Seventeen devices (57%) were
      implanted for non-neurogenic indications including incontinence after
      prostatectomy or hysterectomy. Thirteen devices (43%) were implanted for
      neurogenic conditions including spina bifida, spinal cord injury or severe pelvic
      trauma. The primary end point measured was continence. Secondary end points
      included mechanical and non-mechanical device failure, re-operation and
      complication rates between the two groups. RESULTS: In the neurogenic group, only
      two patients (15%) have their original device in situ without revisions. Only
      three patients (23%) in this group are entirely dry. In contrast, seven patients
      (41%) in the non-neurogenic group are completely dry with their original device
      in situ. A further four (23%) are entirely dry after device revision or
      replacement surgery. The rates of mechanical failure were not statistically
      different between the two groups. The rate of non-mechanical failure (NMF) was
      statistically greater in the neurogenic group in comparison to that in the non
      neurogenic group (p < 0.05). CONCLUSIONS: Insertion of an AMS 800 artificial
      sphincter remains a durable means of regaining urinary continence. Patients who
      are incontinent as a result of an underlying neurological deficit should be
      counselled that they might have a higher risk of non-mechanical device failure,
      requirement for re-operation and that their overall long-term continence rates
      may be poor.

PMID- 14700118
TI  - Cryptorchidism: a general surgical perspective.
AB  - BACKGROUND: The treatment of cryptorchidism has changed, with surgery now
      advocated before the age of two years. Delayed treatment affects fertility,
      malignant potential and psychological stress. AIMS: To assess the pattern of
      referral of cryptorchid patients to a surgical clinic, management and follow-up.
      METHODS: A four-year review of 114 cryptorchid patients examined age at
      presentation, waiting time, timing of surgery and length of follow-up. RESULTS:
      The mean age at presentation to the surgical clinic was 6.7 years (neonatal to
      71). The mean age at orchidopexy was 5.6 years. Seventy per cent had a surgical
      procedure within eight weeks of presentation to a surgeon. Seven per cent were
      kept under surveillance until a maximum age of three years before orchidopexy was
      considered. Only 29% proceeded to surgery before the age of two. Seventeen were
      referred to a paediatric urology unit for further management. CONCLUSIONS:
      Orchidopexy seems prudent between one and two years of age. Only one-quarter of
      patients underwent early orchidopexy. It is vital that it is detected early, by
      paediatricians at birth or the general practitioners (GPs) at the six-week check
      up. Prompt referral to a surgeon with a paediatric interest is essential in order
      to permit surveillance or surgery.

PMID- 14700119
TI  - Tibial shaft fractures treated with the AO unreamed tibial nail.
AB  - BACKGROUND: The AO unreamed tibial nail (UTN) has been used for both open and
      closed tibial fractures. The reported results have been mixed. We evaluated its
      outcome in our unit. AIM: To assess the outcome of tibial shaft fractures treated
      with the AO UTN. METHODS: Forty-eight patients underwent intramedullary nailing
      between 1995 and 2000 using the AO UTN. Follow-up details were available for 45
      patients. RESULTS: Forty-four fractures united (97%). Complications included one
      non-union (2.2%), 15 delayed unions (33%), nine had either broken or bent
      interlocking screws (20%), six malunions (13%) and three patients underwent
      fasciotomy for compartment syndrome (7%). Twenty-one patients underwent at least
      one additional operation to obtain union (47%). Of these, five underwent exchange
      nailing (11%). CONCLUSIONS: The AO UTN does have a high complication rate and,
      should it be used, we feel that early dynamisation or exchange nailing be
      considered to hasten union and prevent screw breakage.

PMID- 14700120
TI  - Botulism as a cause of respiratory failure in injecting drug users.
AB  - BACKGROUND: Wound botulism occurs as a consequence of inoculation of Clostridium
      botulinum spores into a wound. AIM: To describe such a case of wound botulism.
      RESULTS: A 23-year-old drug-injecting user presented with bulbar symptoms and
      progressive signs over a three-day period. The diagnosis of botulism was
      suspected and was treated with large doses of penicillin and botulinum antitoxin.
      The diagnosis was confirmed by the presence of serum botulinum toxin A.
      CONCLUSION: Physicians should be aware of the association of botulism in
      injecting drug users, particularly in Ireland.

PMID- 14700121
TI  - Laparoscopic repair of a strangulated Bochdalek hernia.
AB  - BACKGROUND: Bochdalek herniae are rare. They are usually repaired by open
      abdominal surgery or by a thoracic video-assisted approach. When strangulated and
      in a compromised patient the options are fewer. AIM: To describe a case treated
      by a laparoscopic approach. RESULTS: The procedure was technically difficult, but
      the patient recovered without recurrence. CONCLUSION: Laparoscopic repair is
      possible even with strangulation.

PMID- 14700122
TI  - Laurence Stephen Lowry and Asperger's syndrome.

PMID- 14700124
TI  - Irish neonatal mortality statistics for 2000.

PMID- 14700123
TI  - An Irish statistician's analysis of the national tuberculosis problem--Robert
      Charles Geary (1896-1983).

PMID- 14700125
TI  - Medical and non-medical personnel in public health.

PMID- 14700126
TI  - Reactive airway dysfunction syndrome in Ireland.

PMID- 14700127
TI  - A case of pancreatic carcinoma with a favourable response to treatment.

PMID- 14700128
TI  - Ankle injuries and orthopaedic workload.

PMID- 14700129
TI  - Oral-activated charcoal in the diagnosis of enterovesical fistulae.

PMID- 14700130
TI  - Emission and fate assessment of methyl tertiary butyl ether in the Boston area
      airshed using a simple multimedia box model: comparison with urban air
      measurements.
AB  - Expected urban air concentrations of the gasoline additive methyl tertiary butyl
      ether (MTBE) were calculated using volatile emissions estimates and screening
      transport models, and these predictions were compared with Boston, MA, area urban
      air measurements. The total volatile flux of MTBE into the Boston primary
      metropolitan statistical area (PMSA) airshed was calculated based on estimated
      automobile nontailpipe emissions and the Universal Quasi-Chemical Functional
      Group Activity Coefficient computed abundance of MTBE in gasoline vapor. The fate
      of MTBE in the Boston PMSA was assessed using both the European Union System for
      the Evaluation of Substances, which is a steady-state multimedia box model, and a
      simple airshed box model. Both models were parameterized based on the
      meteorological conditions observed during air sampling in the Boston area.
      Measured average urban air concentrations of 0.1 and 1 microg/m3 MTBE during
      February and September of 2000, respectively, were comparable to corresponding
      model predictions of 0.3 and 1 microg/m3 and could be essentially explained from
      estimated temperature-dependent volatile emissions rates, observed average wind
      speed (the airshed flushing rate), and reaction with ambient tropospheric
      hydroxyl radical (*OH), within model uncertainty. These findings support the
      proposition that one can estimate gasoline component source fluxes and use simple
      multimedia models to screen the potential impact of future proposed gasoline
      additives on urban airsheds.

PMID- 14700131
TI  - Methods for quantifying variability and uncertainty in AP-42 emission factors:
      case studies for natural gas-fueled engines.
AB  - Quantitative methods for characterizing variability and uncertainty were applied
      to case studies of oxides of nitrogen and total organic carbon emission factors
      for lean-burn natural gas-fueled internal combustion engines. Parametric
      probability distributions were fit to represent inter-engine variability in
      specific emission factors. Bootstrap simulation was used to quantify uncertainty
      in the fitted cumulative distribution function and in the mean emission factor.
      Some methodological challenges were encountered in analyzing the data. For
      example, in one instance, five data points were available, with each data point
      representing a different market share. Therefore, an approach was developed in
      which parametric distributions were fitted to population-weighted data. The
      uncertainty in mean emission factors ranges from as little as approximately +/
      10% to as much as -90 to +180%. The wide range of uncertainty in some emission
      factors emphasizes the importance of recognizing and accounting for uncertainty
      in emissions estimates. The skewness in some uncertainty estimates illustrates
      the importance of using numerical simulation approaches that do not impose
      restrictive symmetry assumptions on the confidence interval for the mean. In this
      paper, the quantitative method, the analysis results, and key findings are
      presented.

PMID- 14700132
TI  - An environmental decision-making tool for evaluating ground-level ozone-related
      health effects.
AB  - A computer model called the Ozone Risk Assessment Model (ORAM) was developed to
      evaluate the health effects caused by ground-level ozone (O3) exposure. ORAM was
      coupled with the U.S. Environmental Protection Agency's (EPA) Third-Generation
      Community Multiscale Air Quality model (Models-3/CMAQ), the state-of-the-art air
      quality model that predicts O3 concentration and allows the examination of
      various scenarios in which emission rates of O3 precursors (basically, oxides of
      nitrogen [NOx] and volatile organic compounds) are varied. The principal analyses
      in ORAM are exposure model performance evaluation, health-effects calculations
      (expected number of respiratory hospital admissions), economic valuation, and
      sensitivity and uncertainty analysis through a Monte Carlo simulation. As a
      demonstration of the system, ORAM was applied to the eastern Tennessee region,
      and the entire O3 season was simulated for a base case (typical emissions) and
      three different emission scenarios. The results indicated that a synergism occurs
      when reductions in NOx emissions from mobile and point sources were applied
      simultaneously. A 12.9% reduction in asthma hospital admissions is expected when
      both mobile and point source NOx emissions are reduced (50 and 70%, respectively)
      versus a 5.8% reduction caused by mobile source and a 3.5% reduction caused by
      point sources when these emission sources are reduced individually.

PMID- 14700133
TI  - The Southeastern Aerosol Research and Characterization Study: part 1--Overview.
AB  - This paper presents an overview of a major, long-term program for tropospheric
      gas and aerosol research in the southeastern United States. Building on three
      existing ozone (O3)-focused research sites begun in mid-1992, the Southeastern
      Aerosol Research and Characterization Study (SEARCH) was initiated in mid-1998 as
      a 7-year observation and research program with a broader focus including aerosols
      and an expanded geographical coverage in the Southeast. The monitoring network
      comprises four urban-rural (or urban-suburban) site pairs at locations along the
      coast of the Gulf of Mexico and inland, including two moderately sized and two
      major urban areas (Pensacola, FL; Gulfport, MS; Atlanta, GA; and Birmingham, AL).
      The sites are equipped with an extensive suite of instruments for measuring
      particulate matter (PM), gases relevant to secondary O3 and the production of
      secondary aerosol particles, and surface meteorology. The measurements taken to
      date have added substantially to the knowledge about the temporal behavior and
      geographic variability of tropospheric aerosols in the Southeast. Details are
      presented in four papers to follow.

PMID- 14700134
TI  - Forecasting peak daily ozone levels: part 2--A regression with time series errors
      model having a principal component trigger to forecast 1999 and 2002 ozone
      levels.
AB  - A modified time series approach, a Box-Jenkins regression with time series errors
      (RTSE) model plus a principal component (PC) trigger, has been developed to
      forecast peak daily 1-hr ozone (O3) in real time at the University of Wisconsin
      Milwaukee North (UWM-N) during 1999 and 2002. The PC trigger acts as a predictor
      variable in the RTSE model. It tries to answer the question: will the next day be
      a possible high O3 day? To answer this question, three PC trigger rules were
      developed: (1) Hi-Low Checklist, (2) Discriminant Function Approach I, and (3)
      Discriminant Function Approach II. Also, a pure RTSE model without including the
      PC trigger and a persistence approach were tested for comparison. The RTSE model
      with DFA I successfully forecast the only two 1-hr federal exceedances (124 ppb),
      one in 1999 and one in 2002. In terms of the O3 100-ppb exceedances, 60-80% of
      the incorrect forecasts occurred with incorrect PC decisions. A few others may
      have been caused by unexpected O3-weather relations. When the three approaches
      used UWM-N data to forecast a 100-ppb exceedance somewhere in the Milwaukee, WI,
      metropolitan area, their performance was dramatically improved: the false alarm
      rate was reduced from 0.89 to 0.44, and the probability of detection was
      increased from 0.71 to 0.88.

PMID- 14700135
TI  - Atmospheric particulate matter and polycyclic aromatic hydrocarbons for PM10 and
      size-segregated samples in Bangkok.
AB  - Air samples of particulate matter (PM) with an aerodynamic diameter less than 10
      microm (PM10) were collected from six sites in Bangkok, Thailand, using high
      volume air samplers. Daily samples were taken at intervals of 12 days from
      November 1999 to November 2000. Size-selected sampling using a multislit Andersen
      size-fractionated cascade impactor was undertaken at one site in central Bangkok
      to identify particulate size distribution. The annual average PM10 concentration
      at all six sites exceeded the Thailand National Ambient Air Quality Standard
      (NAAQS) of 50 microg/m3. The daily PM10 concentrations at heavy traffic roadside
      areas ranged between 30 and 160 microg/m3. The highest PM10 level occurred during
      the winter period (November-February), which is the dry season. From our results,
      which are based on a 1-yr survey, it can be observed that the particulate
      concentrations are associated with traffic volumes and seasonal factors
      (temperature and rainfall). The relative importance of size fractions in
      contributing to PM load is presented and discussed. Twenty polycyclic aromatic
      hydrocarbons (PAHs) associated with PM have been identified and quantified. The
      summed PAHs based on the 20 species had an average concentration of 60 ng/m3.
      Benzo(e)pyrene, indeno(123cd)pyrene, and benzo(ghi)perylene were the major
      compounds with average concentrations of 8, 10, and 13 ng/m3, respectively.
      Results indicate that more than 97% of PAHs were found in the small particulate
      size range of <0.95 microm.

PMID- 14700136
TI  - Determination of atmospheric nitrogen input to Lake Greenwood, South Carolina:
      part 2--Gaseous measurements and modeling.
AB  - The Reedy River branch of Lake Greenwood, SC, has repeatedly experienced
      summertime algal blooms, upsetting the natural system. A series of experiments
      were carried out to investigate atmospheric nitrogen (N) input into the lake. N
      was examined because of the insignificant phosphorus dry atmospheric flux and the
      unique nutrient demands of the dominant algae (Pithophora oedogonia) contributing
      to the blooms. Episodic atmospheric measurements during January and March 2001
      have shown that the dry N flux onto the lake ranged from 0.9 to 17.4 kg N/ha-yr,
      and on average is caused by nitric acid (HNO3; 31%), followed by nitrogen dioxide
      (NO2; 23%), fine ammonium (NH4+; 20%), coarse nitrate (NO3-; 16%), fine NO3 (5%),
      and coarse NH4+ (5%). Similar measurements in Greenville, SC (the upper watershed
      of the Reedy River), showed that the dry N deposition flux there ranged from 1.4
      to 9.7 kg N/ha-yr and was mostly caused by gaseous deposition (40% NO2 and 40%
      HNO3). The magnitude of this dry N deposition flux is comparable to wet N flux as
      well as other point sources in the area. Thermodynamic modeling showed low
      concentrations of ammonia, relative to the particulate NH4+ concentrations.

PMID- 14700137
TI  - Particulate matter in California: part 1--Intercomparison of several PM2.5, PM10
      2.5, and PM10 monitoring networks.
AB  - It will be many years before the recently deployed network of fine particulate
      matter with an aerodynamic diameter less than 2.5 microm (PM2.5) Federal
      Reference Method (FRM) samplers produces information on nonattainment areas,
      trends, and source impacts. However, data on PM2.5 and its major constituents
      have been routinely collected in California for the past 20 years. The California
      Air Resources Board operated as many as 20 dichotomous (dichot) samplers for
      PM2.5 and coarse PM (PM10-2.5). The California Acid Deposition Monitoring Program
      (CADMP) collected 12-h-average PM2.5 and PM10 from 1988 to 1995 at ten urban and
      rural sites and 24-h-average PM2.5 at five urban sites since 1995. Beginning in
      1994, the Children's Health Study collected 2-week averages of PM2.5 in 12
      communities in southern California using the Two-Week Sampler (TWS). Comparisons
      of collocated samples establish relationships between the dichot, CADMP, and TWS
      samplers and the 82-site network of PM2.5 FRM samplers deployed since 1999 in
      California. PM mass data from the different monitoring programs have modest to
      high correlation to FRM mass data, fairly small systematic biases and negative
      proportional biases ranging from 7 to 22%. If the biases are taken into account,
      all of the programs should be considered comparable with the FRM program. Thus,
      historical data can be used to develop long-term PM trends in California.

PMID- 14700138
TI  - Particulate matter in California: part 2--Spatial, temporal, and compositional
      patterns of PM2.5, PM10-2.5, and PM10.
AB  - Geographic and temporal variations in the concentration and composition of
      particulate matter (PM) provide important insights into particle sources,
      atmospheric processes that influence particle formation, and PM management
      strategies. In the nonurban areas of California, annual-average PM2.5 and PM10
      concentrations range from 3 to 10 microg/m3 and from 5 to 18 microg/m3,
      respectively. In the urban areas of California, annual-averages for PM2.5 range
      from 7 to 30 microg/m3, with observed 24-hr peaks reaching levels as high as 160
      microg/m3. Within each air basin, exceedances are a mixture of isolated events as
      well as periods of elevated PM2.5 concentrations that are more prolonged and
      regional in nature. PM2.5 concentrations are generally highest during the winter
      months. The exception is the South Coast Air Basin, where fairly high values
      occur throughout the year. Annual-average PM2.5 mass, as well as the
      concentrations of major components, declined from 1988 to 2000. The declines are
      especially pronounced for the sulfate (SO4(2-)) and nitrate (NO3-) components of
      PM2.5 and PM10) and correlate with reductions in ambient levels of oxides of
      sulfur (SOx) and oxides of nitrogen (NOx). Annual averages for PM10-2.5 and PM10
      exhibited similar downwind trends from 1994 to 1999, with a slightly less
      pronounced decrease in the coarse fraction.

PMID- 14700139
TI  - Comparison of the 1-hr and 8-hr National Ambient Air Quality Standards for ozone
      using Models-3.
AB  - In 1997, the U.S. Environmental Protection Agency revised the National Ambient
      Air Quality Standard governing ozone (O3), adding an 8-hr standard of 0.08 ppm
      and phasing out the 1-hr requirement of 0.12 ppm. The 8-hr standard is intended
      to provide greater protection for human health. This research examines spatial
      and temporal patterns of exceedances of the standards using monitoring data and
      modeled estimates. The Penn State/National Center for Atmospheric Research
      Mesoscale Model and Models-3 framework were used to estimate hourly O3
      concentrations for 4-km resolution in the Maryland/Virginia/Delaware/Washington,
      DC, and northern Georgia domains. Results reveal that the spatial and temporal
      nature of compliance is considerably different under the 8-hr standard. In the
      modeling simulations, the 8-hr standard was exceeded 2-5.2 times more often and
      in a 1.8-16.2 times larger area than the 1-hr standard. The 8-hr standard was
      exceeded in areas that generally comply with the 1-hr standard and are not well
      covered by the monitoring network. These results imply that a larger population
      resides in areas with unhealthy O3 levels than noncompliance with the original 1
      hr standard suggests. For the MD/VA/DE/DC domains, 80 and 98% of the total
      population live in areas with 8-hr National Ambient Air Quality Standards (NAAQS)
      exceedances for the 1990 and 1995 episodes, respectively.

PMID- 14700140
TI  - Predicting outcome in pediatric near-drowning.
AB  - BACKGROUND: Near-drowning is common in children and has a high mortality rate.
      Some survivors remain in a vegetative state after the accident and are a great
      burden to their family and society. OBJECTIVES: To find out whether outcomes on
      near drowning can be reliably identified early in the course of illness. METHOD:
      Medical records of 72 children admitted to Queen Sirikit National Institute of
      Child Health, Bangkok, Thailand, for treatment of near drowning from January 1993
      to December 2001 were retrospectively studied. Stepwise multivariate discriminant
      analysis was used to identify the power of variables achieving highest overall
      accuracy in minimizing errors for predicting poor outcome in intact survivors.
      RESULTS: The patients were identified into three groups: functionally intact,
      vegetative and dead groups, it was found that a combination of physical
      examination in the emergency department (ED), the need for cardiopulmonary (CPR)
      in the ED, amount of adrenaline given during CPR, and high blood sugar achieved
      an overall accuracy of 83 per cent. When categorizing patients into good outcome
      versus poor outcome (the combination of the vegetative and dead group were the
      poor outcome group). The variables mentioned above achieved an overall accuracy
      of 98 per cent. Good outcome survivors could be correctly predicted with no
      error, but error occurred when poor outcome survivors were predicted to be good
      outcome in 3 per cent. Glasgow coma score > or = 5, the need for CPR in the ED
      and blood sugar > 300 mg/dl were selected clinical variables found to have
      optimum predictive abilities with an overall accuracy of 96 per cent, but showed
      an error of 6 per cent in predicting poor outcome from functional intact
      survivors (unpredicted good outcome). CONCLUSION: From the present study
      discrimination analysis cannot accurately separate all intact survivors from the
      vegetative groups, but can prospectively differentiate unpredicted good outcome
      from vegetative or dead groups. When using only simple clinical classification
      systems, unpredicted good outcome patients are detected. Since outcome cannot be
      accurately predicted in the ED, all near drowning victims should receive vigorous
      and aggressive treatment in the early course of illness and need close monitoring
      for respiratory complications and neurological signs.

PMID- 14700141
TI  - Molecular diagnosis of Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia
      and feeding problems in infancy, developmental delay, hyperphagia with obesity,
      short stature, hypogonadism, characteristic facial appearance, and behavior
      problems. The diagnosis of PWS is based on clinical findings that change with
      age. PWS has proved to be a difficult condition to recognize with the diagnosis
      often being delayed until later childhood or even adulthood. Therefore, a
      molecular testing for PWS is needed to confirm the diagnosis. OBJECTIVE: To study
      the clinical features of Prader-Willi syndrome patients and confirm diagnosis by
      molecular testing. MATERIAL AND METHOD: Eighteen Prader-Willi syndrome patients
      who were diagnosed between March, 1997 and February, 2002 at the Genetic Unit,
      Queen Sirikit National Institute of Child Health, Bangkok. Peripheral blood
      lymphocytes were obtained and cultured using the standard technique for
      chromosome analysis. For fluorescence in situ hybridization (FISH) studies, the
      specific DNA probes for loci small nuclear ribonucleoprotein polypeptide N
      (SNRPN) were used to detect deletion. Non-deleted cases were confirmed to have
      PWS by methylation analysis. RESULTS: The diagnosis of eighteen PWS patients was
      confirmed by FISH using DNA probes for loci SNRPN demonstrating a deletion of
      chromosome 15q11-q13 in fourteen cases (77%). Four cases (23%) were confirmed to
      have PWS resulting from maternal uniparental disomy by demonstrating exclusively
      maternal specific DNA methylation patterns. CONCLUSION: The clinical diagnosis of
      PWS should be confirmed by molecular testing especially in the infancy period to
      avoid needless invasive diagnostic testing.

PMID- 14700142
TI  - Balloon atrial septostomy at Queen Sirikit National Institute of Child Health in
      the year 2001.
AB  - BACKGROUND: Balloon atrial septostomy (BAS) is a safe and effective palliative
      procedure for patients with cyanotic congenital heart disease. The first BAS in
      Thailand was performed in 1987 at our institute and there have been many changes
      since that time. OBJECTIVE: To evaluate the immediate and intermediate outcomes
      of BAS in the new century. PATIENTS AND METHOD: Thirty patients who underwent BAS
      from January to December 2001 were included in this study. Epidemiologic data,
      echocardiographic diagnosis, changing techniques from the previous report and the
      clinical course for patients were reviewed. The end point of follow-up for this
      study was December 2002. RESULTS: Thirty patients underwent BAS from January to
      December 2001 with an age range from 1 to 213 days (mean 30.40 +/- 41.97 days).
      BAS was selectively tried via the umbilical vein in 6 cases. This was successful
      in 4 cases. Others were performed successfully via the femoral vein. The most
      common diagnoses were complete transposition of the great arteries (TGA),
      pulmonary atresia (PA) with intact ventricular septumand transposition of the
      great arteries with ventricular septal defect (TGA, VSD) respectively. No
      immediate complications were found in the present study. There were 5 deaths
      prior to surgery and 2 post-operative deaths accounting for a total mortality of
      23.3 per cent. CONCLUSION: BAS is a safe and effective palliative procedure for
      patients with various types of cyanotic congenital heart disease even in infants
      up to 7 months of age. The umbilical venous route can be used effectively without
      significant problems. Although the overall mortality is high, it is not related
      to BAS.

PMID- 14700143
TI  - Tubularized, incised plate urethroplasty in hypospadias repair: experience at
      Queen Sirikit National Institute of Child Health.
AB  - BACKGROUND: Hypospadias is the most common penile anomaly. Many techniques have
      evolved during the past 150 years to address chordee and construct a neourethra.
      The current concept of understanding of chordee and emphasis upon preserving the
      urethral plate have brought hypospadias surgery over the last decade near its
      ultimate goal of a reconstructed penis that is functional and cosmetically
      normal. Warren T Snodgrass primarily reported successful urethral plate
      preservation urethroplasty in 1994. The urethral plate can be primarily
      tubularized without an additional skin flap after a dorsal midline relaxing
      incision is made known as tubularized incised plate urethroplasty. It is
      currently used worldwide by pediatric urologists due to its advantages. The
      authors also performed this technique and initial experience at Queen Sirikit
      National Institute of Child Health, Bangkok, Thailand is reported. MATERIAL AND
      METHOD: 88 of 180 hypospadias boys were treated with tubularized incised plate
      urethroplasty for primary repair of hypospadias over a 24 month period. All had
      moderate to severe chordee. Urethral plate preservation is the principle concept
      of this technique and the entire length of the urethral plate was incised along
      the midline and the neourethra was tubulized over a 6 or 8 Fr. catheter. The
      chordee usually disappeared after the penis was degloved. Dorsal plication was
      performed in mild residual chordee. A subdartos flap was created to cover the
      neourethra and pressure dressing applied with bactracin gauze for 7 days. The
      urethral stent was removed on the 7th post-operative day. RESULTS: The
      tubularized, incised plate urethroplasty was performed in 88 boys, age range from
      6 months to 12 years. The operative time was 60 to 100 minutes. Follow-up was up
      to 18 months. There were 13 distal penile, 60 midshaft and 15 penoscrotal types.
      All penes had excellent cosmetic appearance, even in complicated cases. The
      pinhole and large fistulas were noticed in 10 and 3 penes respectively (14%). All
      fistulas were repaired successfully at a later date. Twenty cases had a mild
      degree of meatal stenosis of which 18 had good response to self meatal dilatation
      by their parents and 2 underwent a meatotomy procedure. No urethral diverticulum
      or stricture was noticed during follow-up. CONCLUSION: Even though high
      percentages of fistula complications were noticed in the authors' experience,
      they seemed to be acceptable and easy to correct. This technique seems to be
      suitable for both distal and proximal hypospadias. The advantages of this
      technique include its simplicity, low complication rate, very good appearance of
      the glans penis and normal meatus in most boys. Tubularized incised plate
      urethroplasty is now the procedure of choice for distal and proximal hypospadias
      repair.

PMID- 14700144
TI  - A comparative study between 10 per cent sulfur ointment and 0.3 per cent gamma
      benzene hexachloride gel in the treatment of scabies in children.
AB  - BACKGROUND: Scabies is a common contagious skin disease in children. Treatment of
      scabies in infants and children is the subject of worldwide concern because of
      risk and benefit of the variety of scabicides. OBJECTIVE: To compare the efficacy
      of 10 per cent sulfur ointment and 0.3 per cent gamma benzene hexachloride gel
      for the treatment of scabies in children. METHOD: A randomized investigator blind
      study was conducted to compare the efficacy of 10 per cent sulfur ointment and
      0.3 per cent gamma benzene hexachloride (GBH) for the treatment of scabies in
      children at Queen Sirikit National Institute of Child Health from December 1999
      to May 2000. Diagnosis was made by the clinical signs of excoriated papules in
      the classic distribution with nocturnal pruritus and family history of similar
      symptoms. Diagnosis for all patients was confirmed by positive skin scrapings for
      eggs, larva, mites or fecal pellets by light microscopy. Patients were followed
      up at intervals of 2 and 4 weeks. RESULTS: One hundred children with an age range
      from 6 months to 13 years were randomized into 2 groups, 10 per cent sulfur group
      (50 cases) and 0.3 per cent GBH (50 cases). Age, sex, history of contact cases
      and clinical manifestations were not statistically different between the two
      groups. After 4 weeks of treatment, there were no statistical differences between
      the two groups in patients assessed cured (92% vs 94%), clinical cure (92% vs
      91%) and parasitic cure (83% vs 84%). The adverse effect of foul odor in the
      sulfur group was more common than in the GBH group (p < 0.05). CONCLUSION: 10 per
      cent sulfur ointment is as safe and efficacious as 0.3 per cent GBH for the
      treatment of scabies in children.

PMID- 14700145
TI  - Effects of multivitamin and folic acid supplementation in malnourished children.
AB  - OBJECTIVE: To study the effect of multivitamin and folic acid supplementation on
      serum folate level and weight gain. MATERIAL AND METHOD: A prospective randomized
      controlled study was conducted in malnourished children at the Nutrition Clinic,
      Queen Sirikit National Institute of Child Health from February to June 2000.
      History taking, weight-height measurement, and blood testing for complete blood
      count (CBC) and serum folate level were done. Patients were randomly by assigned
      into 2 groups. The study group was supplemented daily with multivitamins (MVD)
      along with a folic acid tablet while the control group was supplemented daily
      with MVD only, for 6 weeks. RESULTS: Twenty-nine malnourished children were
      enrolled in the present study. They were randomly by assigned into 2 groups, 14
      children in the study group and 15 children in the control group. There were 11
      boys (38%) and 18 girls (62%). Mean age was 36.3 months. Anemia and low serum
      folate level were found in 24 per cent and 21 per cent respectively. There was no
      significant difference in the data of both groups, except that anemia was more
      common in the study group (p = 0.018). After 6 weeks of supplementation,
      increases in weight and serum folate level were significantly higher in the study
      group, but there was no significant difference in weight increased between both
      groups. CONCLUSION: Folate deficiency may be found in malnourished children.
      Efficacy of folic acid supplement is good. Folic acid needs to be supplemented in
      malnourished children.

PMID- 14700146
TI  - Out-patient antibiotics switch therapy in pediatric urinary tract infection.
AB  - OBJECTIVE: To compare the outcomes of out-patient antibiotics switch therapy with
      the treatment provided in the hospital among pediatric urinary tract infection
      (UTI) cases. MATERIAL AND METHOD: A comparative study was carried out using the
      febrile UTI patients of age 1 month-15 years in the observation room (OPD), Queen
      Sirikit National Institute of Child Health, Bangkok, Thailand, from 1st January
      2000 to 31st December 2000 and the admitted pediatric UTI cases during the same
      period. The treatment at the OPD was started with parenteral antibiotics, then
      switched to oral form when the patients were clinically improved and defervesence
      occurred. RESULTS: There were 95 cases of pediatric UTI of which 29 cases were
      treated in the observation room as out-patient, 66 cases were treated as in
      patients after admitting them. The success rate of treatment was the same in both
      groups. The patients in the observation room were fit enough to be discharged but
      continued oral treatment within 1.93 +/- 0.65 days, compared with 6.24 +/- 2.72
      days of the admitted group. Gentamicin and ceftriazone were the two most common
      parenteral antibiotics and norfloxacin was the most commonly prescribed oral
      antibiotics in both group. Mean age of the OPD group (6.24 +/- 2.72 years) was
      higher than the admitted group (0.97 +/- 1.7 year). Escherichia coli (E. coli)
      was the most commonly found organism in the urine culture and the sensitivity
      pattern was the same in both groups. CONCLUSION: The study revealed that some
      pediatric UTI patients can be treated as out-patients using antibiotics switch
      therapy in the observation room instead of being admitted.

PMID- 14700148
TI  - Successful amblyopia therapy by using synoptophore.
AB  - BACKGROUND: Amblyopia is the most common cause of monocular visual impairment in
      children. Even though occlusion therapy is the treatment of choice, the success
      rate has not been well achieved due to poor compliance. Other alternative
      treatments have been tried for a better outcome. OBJECTIVE: To report successful
      therapy for amblyopia using synoptophore. METHOD: A retrospective study of 25
      amblyopic children enrolled in the amblyopic treatment program, from September
      18, 1996 to October 14, 2002. The program included patching of the good eye,
      stimulating the amblyopic eye with synoptophore, and recording the visual acuity
      of both eyes each time. All children were regularly examined every 3 months by
      the same ophthalmologist. The compliance of each individual was reassessed and
      adjusted. At the end of the training program, visual acuity of the amblyopic and
      the good eyes were measured, plus the binocularity of both eyes were recorded as
      the main outcome measurement. RESULT: Final (best) visual acuities were between
      20/20 and 20/30 for 19 cases of 21 cases (90%). Final best binocularity was
      maintained in 15 of 25 patients (60%), including 4 anisometropic patients (100%),
      2 ptosis patients (50%), 4 pseudophakic patients (80%), 2 strabismic patients
      (40%), and 3 combined group patients (100%) CONCLUSION: By using synoptophore to
      stimulate the amblyopic eye, while occluding the good eye, it improved the level
      of vision to a certain acceptable degree. Thus, compliance of the treatment can
      be well achieved. However, the understanding and good cooperation of the parents
      were also a must for successful amblyopia therapy.

PMID- 14700147
TI  - Aortic valve prolapse in subpulmonic ventricular septal defect.
AB  - BACKGROUND: Ventricular septal defect (VSD) is the most common congenital heart
      disease worldwide. Subpulmonic type VSD is an interesting subtype due to the
      aortic valve complications rate, which can change the prognosis of the VSD.
      Higher prevalence rates have been reported with this subtype in Eastern countries
      but there has been no report from Thailand so far. OBJECTIVE: 1. To determine the
      prevalence of subpulmonic VSD. 2. To determine the prevalence and demographic
      data of aortic valve prolapse (AVP) and aortic regurgitation (AR) in subpulmonic
      VSD. METHOD: A retrospective study of 1,977 patients with isolated VSD, diagnosed
      from January 1995 to June 2002 at the Cardiology Unit, Queen Sirikit National
      Institute of Child Health was reviewed to differentiate types of VSD. Color flow
      doppler echocardiogram was performed in all cases to confirm the diagnosis and
      differentiate the types of VSD. Patients with subpulmonic VSD were studied to
      find out the presence of the aortic valve prolapse and aortic regurgitation.
      Those who had subpulmonic VSD were called for reevaluation of aortic valve
      complications, from January 2000 to June 2002. MAIN OUTCOME MEASURE: Subpulmonic
      VSD, aortic valve prolapse (AVP) and aortic regurgitation (AR). RESULTS:
      Subpulmonic VSD was diagnosed in 312 cases (17.5%). At the mean age of 3.47 yr,
      AVP was found in 101 cases (32.4%) and AR was found in 54 cases (17.3%) at the
      first echocardiogram. Subsequent echocardiography follow-up showed that the
      overall number of AVP cases was 153 (49%) and AR was 84 (26.9%) at the mean age
      of 5.5 and 6.3 year respectively. CONCLUSION: The prevalence of subpulmonic VSD
      was high among Thai children. Aortic valve complication is common in this group
      and can occur from early infancy. The present findings support the progressive
      increase in this complication with age.

PMID- 14700149
TI  - A comparison of oral ibuprofen and intravenous indomethacin for closure of patent
      ductus arteriosus in preterm infants.
AB  - BACKGROUND: Indomethacin is widely accepted as the treatment for patent ductus
      arteriosus (PDA) in preterm infants but it has various side effects. Ibuprofen is
      the alternative treatment and believed to be less likely to induce side effects.
      OBJECTIVE: To compare efficacy and side effects of ibuprofen versus indomethacin
      treatment for symptomatic patent ductus arteriosus (PDA) in preterm infants.
      METHOD: The authors studied 30 infants (gestational age < or = 35 weeks, aged <
      or = 10 days) who were diagnosed as having symptomatic PDA confirmed by
      echocardiogram. The infants were randomly assigned to receive three intravenous
      doses of indomethacin given at 12-hour intervals or three doses of ibuprofen
      given at 24-hour intervals, starting within ten days of life. The demographic
      data, rate of clinical closure, need for additional treatment, side effects,
      complications and the infants' clinical course were recorded within 28 days.
      RESULTS: The rate of ductal closure was similar with the two treatment regimes.
      Ductal closure occurred in 7 of 15 infants given ibuprofen (46.67%) and 10 of 15
      infants given indomethacin (66.67%). (Relative risk 0.669; 95% confidence
      interval, 0.328 to 1.364; p = 0.462) The number of infants who needed a second
      pharmacologic treatment was not significantly different between the two groups,
      (6 cases in the ibuprofen group, 5 cases in the indomethacin group) but surgical
      ligation was performed in two cases in the indomethacin group. There was a
      significant difference in using the diuretic drug (furosemide) in the
      indomethacin group (11 cases), compared to the ibuprofen group (3 cases), (p =
      0.009). More cases of necrotizing enterocolitis were seen in the indomethacin
      group (66.67% compared to 40% in the ibuprofen group) but there was no
      statistically significant difference. CONCLUSION: Ibuprofen has the same
      efficiency as indomethacin for the treatment of symptomatic patent ductus
      arteriosus in preterm infants and less likely to induce necrotizing enterocolitis
      and renal toxicity than indomethacin.

PMID- 14700150
TI  - Medication errors at Queen Sirikit National Institute of Child Health.
AB  - BACKGROUND: In the past two years, medication errors have been recognized as
      having been unacceptably high among hospitalized patients. OBJECTIVE: To
      determine the incidence and type of medication errors, severity of events,
      patient outcomes and categories of drugs involved in the largest pediatric
      hospital in Thailand over a fifteen-month-period. PATIENTS AND METHOD:
      Retrospective review of in-patient medication errors documented in standard
      reporting forms from September 2001 to November 2002. Main outcome measure was
      the incidence of errors reported. RESULTS: Medication errors occurred in 1 per
      cent of admissions (322 errors of 32,105 admissions). The most common error type
      was prescription error (35.40%). The majority of errors were detected and
      prevented before the drugs were administered (76.71%). There was only one case of
      permanent brain damage; no deaths occurred in the study period. The most common
      group of drugs involved in medication errors was antibiotics and the most common
      route of administration was oral. CONCLUSION: Medication errors are not uncommon.
      There is a need to change the behaviors of recognizing and acknowledging clinical
      errors, including drug errors. Careful review of errors highlights the many
      opportunities to change how drug errors are addressed and to make them less
      likely.

PMID- 14700151
TI  - A community-based thalassemia prevention and control model in northern Thailand.
AB  - OBJECTIVE: To describe a community-based model for prevention and control of
      thalassemias and haemoglobinopathies in northern Thailand. DESIGN: Operational
      research composed of two components. First, a model to test whether thalassemic
      cases and carriers could be retrospectively detected from school children.
      Second, a model for prevention of prospective cases of thalassemic babies among
      pregnant women. SETTING: Phan District of Chiang Rai Province in northern
      Thailand. SUBJECTS: Component one: 5,617 preschool children and 21,123 school
      children were screened during May and July 1997. Component two: 256 pregnant
      women, 16 weeks or less gestation were screened during January and December 1997.
      MATERIAL AND METHOD: Component one: Sub-district public health officers and
      school teachers were trained to use pictures and simple clinical examination to
      detect suspected thalassemics among preschool and school children. Suspected
      cases were then referred for further clinical examination and blood testing.
      Blood smear examination was done at the Phan Community Hospital but Hb typing
      lusing on electrophoresis was done at the provincial hospital. The cellulose
      acetate was sent for re-reading at the Department of Medical Sciences. Component
      two: Osmotic fragility (OF) and dichlorophenol-indolephenol (DCIP) tests were
      abol in pregnant women (< or = 16 weeks of gestation) in the Phan Community
      Hospital. If OF test was positive, Hb typing was done at a regional medical
      sciences center. Their spouses were also located and tested for Hb typing.
      Prenatal diagnosis was done and therapeutic abortion was offered, if indicated.
      MAIN OUTCOME MEASURES: Cases, carriers, suspected cases, Hb typing, OF and DCIP
      tests. RESULTS: In Component one: 26,740 children were screened of whom 893 cases
      were suspected. Out of those suspected, 296 (33.2%) were normal, 140 (15.6%) were
      diseased, and 457 (51.2%) were carriers. 56 cases had major thalassemia diseases.
      Their parents were counseled. Forty couples were determined to need some form of
      family planning and 39 (97.5%) accepted. In Component two: 256 pregnant women
      were screened and 56 were found to be carriers. Only 45 husbands could be located
      and Hb typed. Five couples were determined to require prenatal diagnosis (PND).
      One happened to undergo therapeutic abortion because of HIV infection in the
      mother without PND. Of the four who underwent PND, one was found to have a fetus
      with major thalassemia. However, this couple refused therapeutic abortion because
      of religious reasons. CONCLUSION: This study combined both prospective and
      retrospective approaches and can be considered successful. However, as the only
      available option for pregnant women with affected fetuses is therapeutic
      abortion, this makes it difficult to expand the program because abortion may not
      be acceptable in certain communities. In addition, this model requires PND and
      other laboratory and clinical facilities as backups. Such backups may not be
      available in certain settings.

PMID- 14700152
TI  - The nutritional status of outpatients at Queen Sirikit National Institute of
      Child Health.
AB  - OBJECTIVE: To study the nutritional status and prevalence of malnutrition in
      outpatients at Queen Sirikit National Institute of Child Health (QSNICH).
      MATERIAL AND METHOD: A cross-sectional study was done in outpatients at the Well
      baby Clinic (WBC) and Outpatient Department (OPD), in May 1999. Patient sex, age,
      weight and length or height were recorded. Per cent weight for age (%W/A), per
      cent height for age (%H/A) and per cent weight for height (%W/H) were determined,
      using Thai standard growth data (1999). RESULT: A total of 3,667 children were
      included in the study including 1,903 well children from the WBC and 1,764 sick
      children from the OPD. The gender distribution was 49 per cent girls and 51 per
      cent boys. Their ages ranged from 10 days to 16 years. Nutritional status was
      classified as normal in 49.4 per cent, underweight in 19.8 per cent, wasting in
      12.4 per cent, stunting in 12.8 per cent, overweight in 15.4 per cent and obesity
      in 10.4 per cent. The prevalence of normal, underweight and wasting status at the
      OPD were significantly higher; whereas, the prevalence of stunting, overweight
      and obesity status were significantly higher at WBC. There were no gender
      differences, except for a higher prevalence of stunting in males (p < 0.05).
      CONCLUSION: Malnutrition is still a health problem in Thai children, both
      undernutrition and overnutrition. Good nutrition must be promoted to prevent
      malnutrition and early detection of malnutrition should be a major concern of
      health care personal with introduction of early intervention.

PMID- 14700153
TI  - Effect of cisapride on corrected QT interval in neonates.
AB  - OBJECTIVE: To evaluate the effect of cisapride on corrected QT (QTc) interval in
      neonates at the Queen Sirikit National Institute of Child Health. METHOD: A
      prospective study was performed to see the effects of cisapride on QTc interval
      in 20 neonates between 1st July 2001 and 31st January 2002. QTc interval was
      determined just before, 48 hours, 7 days and 15 days after the start of treatment
      with cisapride. QTc interval was calculated by averaging QT/square root(RR)
      values obtained from 5 consecutive beats in lead II of the EKG. Baseline
      electrolyte and calcium levels were drawn on all infants before treatment of
      cisapride. Drug dose ranged from 0.1-0.2 mg/kg every 6 to 8 hours. RESULTS:
      Twenty infants were enrolled in the survey but complete data was obtained on 18
      infants only. QTc interval of > 0.45 seconds was not found in any neonate. There
      was no significant difference of QTc interval before and 48 hours, 7 days and 15
      days after cisapride administration (p = 0.861). There were also no statistically
      significant effects of age at starting cisapride, weight, gestational age and
      dose on QTc interval (p = 0.581, 0.65, 0.8, and 0.497). There were no adverse
      effects such as diarrhea or jaundice during the study. CONCLUSION: Term and
      preterm infants using cisapride at the doses of 0.4-0.8 mg/kg/day did not develop
      QTc prolongation, arrhythmias or adverse effects. In the absence of risk factors,
      cisapride may be safe for use in neonates.

PMID- 14700154
TI  - Intussusception associated with a relapsing nephrotic patient: a case report.
AB  - BACKGROUND: Gastrointestinal disturbances are encountered frequently in the
      course of the nephrotic syndrome but intussusception is a rare association. It
      may be the result of incoordinate motility and bowel wall edema. OBJECTIVE: To
      report a case of intussusception associated with relapsing nephrotic syndrome.
      CASE REPORT: The authors reviewed the case of a 5-year-old boy who had been
      diagnosed as having nephrotic syndrome at Queen Sirikit National Institute of
      Child Health for 1 year, who later presented with nephrotic symptoms and an acute
      abdomen. Abdominal ultrasonography and barium enema were performed which
      diagnosed ileo-colic intussusception. Resection of the ileum and appendectomy
      were performed while the relapsing nephrotic syndrome was treated by
      prednisolone. The patient's recovery was excellent. Percutaneous renal biopsy was
      done because of the frequent relapsing condition and showed mesangial
      proliferative glomerulonephritis consistent with IgM nephropathy. Intussusception
      should be included in the differential diagnosis of relapsing nephrotic syndrome
      presenting with acute abdominal pain. Abdominal ultrasonography is helpful in
      confirming this condition.

PMID- 14700155
TI  - Childhood Helicobacter pylori infection, clinical presentations, endoscopic,
      histologic features and results of treatment.
AB  - OBJECTIVE: To study childhood Helicobacter pylori infection concerning the
      clinical presentations, endoscopic, histologic features and results of treatment.
      MATERIAL AND METHOD: A retrospective study conducted at the Gastroenterology and
      Nutrition Unit, Queen Sirikit National Institute of Child Health (QSNICH) was
      done from January 1993 to December 2002. All patients presented with recurrent
      abdominal pain, upper GI bleeding (non-variceal bleeding) chronic vomiting and
      dyspeptic symptoms who underwent upper GI endoscopy were included in this study.
      Positive urease test verified by biopsied specimens from the gastric antrum and
      body and/or finding the organisms from the specimens were the criteria for
      diagnosis of H. pylori infection. Clinical presentations, endoscopic, histologic
      features and results of treatment in H. pylori infected cases were described.
      RESULT: A total of 144 patients who underwent upper GI endoscopy were included in
      the study. 22 out of 144 cases proved to be infected by H. pylori. Ages ranged
      from 2.6 to 14 years (mean age 9 years). The male/female ratio was 1:1.2.
      Vomiting and epigastric pain were the leading symptoms. Endoscopic findings were
      divided into inflammation in the stomach 12 cases, both stomach and duodenum 6
      cases and duodenal ulcer 4 cases. Nodular hyperplasia of gastric antrum was found
      in 8 out of 22 cases. Histologic evidence of chronic gastritis was present in 12
      cases, chronic gastroduodenitis 6 cases and chronic duodenitis in duodenal ulcer
      cases. Treatment regimen consisted of one H2 blocker (ranitidine) initially which
      was changed to omeprazole in 2001 combined with 2 antibiotics (amoxycillin and
      metronidazole) for 14 days. CONCLUSION: This study group represented middle and
      low income groups from around Bangkok and many parts of Thailand. The prevalence
      of H. pylori infection in the present study was 15.3 per cent which reflects that
      H. pylori infection is a common health problem in Thailand. However, because this
      was only a descriptive study, the authors cannot specify the association between
      symptoms, endoscopic findings, histologic features and disease.

PMID- 14700156
TI  - Epigastric heteropagus twins: a report of four cases.
AB  - Epigastric heteropagus twins (EHT) is a rare form of conjoined twins. It refers
      to unequal and asymmetric conjoined twins in which the dependent part (parasite)
      is attached to the epigastrium of the dominant part (autosite). The authors
      herein report four cases of EHT. Omphalocele was present in 3 patients. Surgical
      excision of the parasite and repair of the abdominal wall defect were successful
      in three cases. Three infants had associated cardiac anomalies and one of them
      died during surgery from cardiopulmonary failure.

PMID- 14700157
TI  - Human figure drawing test: validity in assessing intelligence in children aged 3
      10 years.
AB  - BACKGROUND: Human-figure-drawing abilities are related with cognitive development
      in children. As cognitive skills progress, drawing abilities also improve in
      details and sex differentiation. The Goodenough-Harris (G-H) drawing test was
      developed to score human figure drawing with separate norms for males and
      females. OBJECTIVES: To evaluate whether the Goodenough-Harris human drawing test
      is valid to classify intelligence in children aged 3-10 years. MATERIAL AND
      METHOD: Record files of 528 children aged between 3-10 years who had attended the
      Child and Adolescent Unit at Queen Sirikit National Institute of Child Health
      (Children's Hospital), Bangkok, Thailand from January 1999 to December 2001 were
      retrospectively reviewed. Inclusion criteria included: 1) performing the human
      figure drawing test and standard intelligence tests on the same day and 2)
      diagnoses were addressed. RESULTS: The ages of the children ranged from 3 10/12
      years to 10 11/12 years with a mean age of 7 9/12 years, 49.5 per cent were males
      and 50.5 per cent were female. The study group was diagnosed as pervasive
      development disorder 17 per cent, attention deficit hyperactivity disorder 13 per
      cent, and mental retardation 11.3 per cent. Overall correlation of full scale
      intellectual quotient (FSIQ) from the standard intelligence test and standard
      scores on the Goodenough-Harris system was 0.813 (p < 0.01). The overall validity
      of the human figure drawing test in classified correct intellectual level was
      60.8 per cent but in children with an intellectual quotient (IQ) less than 70,
      the correct classification was 69.2 per cent. After stratification by age, it was
      found that the human figure drawing test had validity in predicting IQ below 70
      in 88.7 per cent and 68.8 per cent of children aged < 6 years and aged > 6 years
      respectively. CONCLUSION: The human figure drawing test can be used as an
      additional measure of assessing intelligence in young children but it should not
      be substituted for standard tests. The test is not complicated, therefore,
      trained personnel can use it in combination with other screening tests for
      cognitive development in children.

PMID- 14700158
TI  - Factors effecting the outcome of acute respiratory distress syndrome in pediatric
      patients treated with high frequency oscillatory ventilation.
AB  - OBJECTIVES: To evaluate the survival rate and factors affecting the outcome of
      pediatric patients treated with high-frequency oscillatory ventilation (HFOV) for
      diffuse alveolar disease (DAD) compatible with acute respiratory distress
      syndrome (ARDS). METHOD: A cohort study was conducted at the pediatric intensive
      care unit of Queen Siritkit National Institute of Child Health from 1st January
      1999 to 31st December 2001. Children who suffered from DAD compatible with ARDS
      were enrolled. Inclusion criteria were PaO2/FiO2 < 200 and oxygenation index (OI)
      > 10. High-frequency oscillatory ventilator (3100A Sensor Medics Corp, Yorba
      Linda, Calif) was used applying high volume strategy of treatment. Patients were
      weaned to conventional ventilation (CV) once clinical improvement occurred.
      Demographic data, duration of CV mode before changing to HFOV, duration of HFOV,
      ventilator parameters and gas exchange variables from beginning and during the
      course of HFOV were recorded, so patient data could be compared between surviving
      and non-surviving groups. RESULTS: A total of 21 children were enrolled during
      the 3 year period. There were 4 patients with simultaneous air leak syndrome and
      a total of 10 male patients. The average age was 3.58 +/- 3.9 years. There were
      11 surviving patients (52.4%). Data of ventilator parameters and gas exchange
      variables after changing to HFOV for 4-6 hours for the two groups, FiO2 was
      higher (0.99 +/- 0.32 vs 0.84 +/- 0.18; p = 0.02) and alveolar arterial oxygen
      gradient [P(A-a)O2] was lower (448.5 +/- 140.8 vs 562.7 +/- 99.9 mmHg; p = 0.047)
      in the surviving group than in the non-surviving group. Concerning mean airway
      pressure (Paw), oxygenation index (OI), P(A-a)O2 and PaO2/FiO2 at initiation and
      during the course of HFOV with comparison of the surviving and non-surviving
      groups: Paw and OI decreased in the surviving group and was significantly
      different at 36 and 24 hours respectively. P(A-a)O2 was statistically
      significantly lower at 6 hours after HFOV initiation in the surviving group.
      PaO2/FiO2 was statistically significantly increased at 24 hours in the surviving
      group. CONCLUSION: Implement of HFOV is useful in patients with DAD, ARDS and air
      leak syndrome from the initial phase of illness which fulfill criteria for
      decreasing ventilator induced lung injury and thus decrease the mortality rate
      from ARDS. Predisposing survival factor showing statistically significant
      differences was lower Paw during CV before changing to HFOV, lower Paw at 36
      hours, lower OI at 24 hours, lower P(A-a)O2 at 6 hours and higher PaO2/FiO2 at 24
      hours. These parameters are good indicators for the prognosis of ARDS for
      patients responding or not responding to HFOV.

PMID- 14700159
TI  - Vertical transmission of dengue infection in Thai infants: two case reports.
AB  - Dengue infection is hyperendemic in tropical countries especially in Thailand.
      Most dengue infections occur during childhood but some adults may remain
      susceptible to infection. About 30 per cent of dengue infection are reported in
      patients > 15 years old. Some pregnant women may also be susceptible to dengue
      and if they experience dengue infection, they can transmit the dengue viruses to
      their babies. The authors report two babies who developed mild dengue illness,
      dengue hemorrhagic fever (DHF) grade II, beginning on their 6th day of life. Both
      of them had low grade fever, hepatomegaly and generalized petechial rash. The
      first baby had Hct ranging from 46 to 40 per cent with minimal right pleural
      effusion. The lowest platelet count was 19,000 cells/mm3. His mother had dengue
      shock syndrome with masssive post partum bleeding. The second baby had dengue 2
      infection while his mother had dengue fever. His Hct had also risen from 52 per
      cent to 61 per cent with right pleural effusion. His lowest platelet count was
      7,000 cells/mm3. Both mothers and their babies had a complete recovery although
      the first baby had prolonged thrombocytopenia for two months.

PMID- 14700160
TI  - Conjoined twins: surgical separation in 11 cases.
AB  - Eleven pairs of symmetrically conjoined twins underwent surgical separation at
      the Queen Sirikit National Institute of Child Health. Six were omphalopagus, 4
      were thoracopagus and 1 was pygopagus. Eight were female and 3 were male. Three
      pairs were separated on emergency or semi-emergency bases, and the remaining 8
      pairs were separated electively at an older age. Of the 3 pairs who had early
      emergency separations, one pair, whose combined birth weight was only 2,500 g,
      underwent emergency separation at the age of 44 days after the death of one twin.
      The second twin also expired one hour after the separation. In the remaining 2
      pairs, early separation was done because of the deterioration of one twin due to
      complex cardiac anomalies. In both cases, the infants with cardiac anomalies
      expired but the others survived the separation satisfactorily. In one pair of
      thoracopagus conjoined twins, one twin had cyanotic cardiac anomalies. They were
      electively separated at the age of 2 years and 9 months. The twin with cardiac
      anomalies expired 2 hours after surgery, but the other survived the separation
      satisfactorily. In the remaining 7 pairs who underwent elective separations, both
      twins of each pair survived the separation satisfactorily. However, one twin
      expired unexpectedly 10 days after the separation.

PMID- 14700161
TI  - Splenic lymphangioma and presentation with frequent urination: a case report.
AB  - Lymphangioma of the spleen is a rare disorder with a clinical manifestation
      ranging from incidental findings of an abdominal mass to symptomatic abdominal
      pain. The authors reported a case of splenic lymphangioma with the presenting
      symptom of frequent urination in a 9-year-old boy. A large firm mass was found at
      the left upper quadrant, 12 cm in diameter. The diagnosis was confirmed by
      ultrasonography and computerized tomographic (CT) scan. The symptoms of frequent
      urination disappeared after operative splenectomy. No evidence of recurrence
      occurred over a 3-year follow-up.

PMID- 14700162
TI  - Childhood asthma: proper managements do reduce severity.
AB  - RATIONALE: Asthma is an increasing problem, both in children and adults which is
      due to an increase in environmental pollution. The current management of
      asthmatic patients is different from the previous decade as more understanding of
      the mechanism of asthma pathology is known. OBJECTIVES: To study the prevalence
      of hospitalized asthmatic patients of different age groups in the past decade and
      to compare the results of different treatments during each 5-year period, 1986
      1990, 1991-1995 and 1997-2001. MATERIAL AND METHOD: A retrospective review of the
      Out-patient Department (OPD) and In-patient Department (IPD) cases of asthma
      patients, sorted by International Classification of Diseases (ICD 9 & 10) at the
      Queen Sirikit National Institute of Child Health (QSNICH), previously known as
      Children's Hospital was carried out. The patients were divided into 3 groups
      according to the 5-year period of admissions: 1986-1990, 1991-1995 and 1997-2001.
      Comparison of the prevalence, age distribution, management, severity and outcomes
      of the patients in different groups using the standard statistical package SPSS
      for windows. RESULTS: The prevalence of asthma increased from 7,476 OPD visits in
      1986 to the peak of 15,576 visits in 1997 and about 13,000-14,000 stable visits
      from 1998 through 2001. About 2-3 per cent of these OPD cases were admitted to
      the hospital. After the hospital charts had been reviewed, 2,927 cases of true
      asthma cases (81.9%) were studied and they were divided into 3 groups, group 1, 2
      and 3 consisting of 1,140, 716 and 1,071 patients, respectively. About 60-80 per
      cent of the admitted cases were children under 5 years old. With the different
      management of hospitalized cases between the 3 periods, a significant reduction
      in the readmission rate was outstanding from 14 per cent to 5 per cent and the
      maximum number of readmissions was reduced from 8 times to 5 times (the majority
      was 2 times). The length of stay and the percentage of complicated respiratory
      failure cases were not different. CONCLUSION: The asthma prevalence is
      increasing. Young children 0-2 years of age tend to have more severe diseases
      that need hospitalization. Current management, inhaled beta 2 agonists, together
      with anti-inflammatory drugs do reduce asthma severity to a certain degree. Early
      intervention of controller medications and regular follow-up care do reduce the
      readmissions. Further newer treatment of asthma is required for better outcomes
      of these asthmatic patients.

PMID- 14700163
TI  - Treatment of Kawasaki disease using locally product intravenous immunoglobulin.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute febrile illness of unknown origin.
      Several kinds of IVIG have been shown to be effective in the decrease of the
      incidence of coronary artery abnormalities (CAA) which is the most serious
      complication. Nowadays, the National Blood Centre, Thai Red Cross Society can
      manufacture IVIG from the plasma of Thai blood donors which is much cheaper than
      the imported intravenous immunoglobulin (IVIG's). The effectiveness of this Thai
      Red-Cross IVIG in Kawasaki disease has never been documented. OBJECTIVE: To
      determine the initial treatment response and prevalence of CAA in KD treated with
      a high dose (2 g/kg) of Thai Red-Cross IVIG. PATIENTS AND METHOD: All patients
      with a diagnosis of KD who had initial treatment with 2 g/kg of Thai Red-Cross
      IVIG at Queen Sirikit National Institute of Child Health from December 2001 to
      February 2003 were reviewed retrospectively. RESULTS: All 22 cases (100%) had
      good response to a single treatment with a high dose of IVIG. The only patient
      who did not complete the IVIG treatment had a severe reaction following the
      administration of the drug and needed discontinuation and intervention. During
      the convalescent phase, there were only 2 cases (9.09%) with CAA in the first
      month and 1 case (4.55%) at the 3-month follow-up. This only case with CAA at 3
      months had multiple aneurysms at the left main and left anterior descending
      coronary arteries. No giant aneurysms were found in the present study.
      CONCLUSION: The efficacy of a high dose (2 g/kg) of Thai Red-Cross IVIG in
      Kawasaki disease is excellent. However, the severe reaction in one patient needs
      further surveillance.

PMID- 14700164
TI  - Causes of femoral shaft fracture in children under five years of age.
AB  - OBJECTIVE: To study the causes of femoral shaft fracture in children younger than
      5 years of age. STUDY DESIGN: Retrospective, descriptive study. PATIENTS AND
      METHOD: Medical records and radiographs of 39 children younger than 5 years of
      age with femoral shaft fractures treated in Queen Sirikit National Institute of
      Child Health during the years 1996-2001 were reviewed. The responsible causes for
      the femoral shaft fracture given by caretakers by interview were collected.
      RESULTS: The most common history was falling or jumping from a height (36%)
      followed by traffic accidents (26%) and object or person falling on top of them
      (23%) respectively. Only one case presented with a history of abuse. Nine cases
      were suspected of abuse, but, without further investigations it was not possible
      to identify the exact cause of fracture. CONCLUSION: Histories given by
      caretakers for the cause of femoral shaft fracture in children younger than 5
      years of age are varied. The orthopedists should find out the exact cause of
      fracture to prevent missed or delayed diagnosis of abuse that may have occurred.

PMID- 14700165
TI  - Bilateral asynchronous humeral shaft fractures in a patient with autosomal
      dominant osteopetrosis type II (Albers-Schonberg disease).
AB  - Osteopetrosis is a rare metabolic disease which presents with fragile
      osteosclerotic bone. A thirteen-year-old girl with an underlying autosomal
      dominant osteopetrosis (ADO) type II who sustained a left oblique humeral shaft
      fracture after trivial trauma is presented. Radiographic results showed many
      characteristic features of osteopetrosis, including incomplete remodeling of a
      previous fracture of the contralateral humeral shaft. The authors obtained good
      healing and alignment of the left humeral shaft fracture by sugar tong slab.

PMID- 14700166
TI  - Clinical presentations of dengue hemorrhagic fever in infants compared to
      children.
AB  - BACKGROUND: Dengue infections are endemic in Thailand. Infants are at risk of
      developing dengue fever (DF) and dengue hemorrhagic fever (DHF). Many infants
      have severe DHF with unusual manifestations and may suffer from complications and
      even death because of difficulties in early diagnosis and improper management.
      OBJECTIVE: To study the incidence of infants DHF and to compare clinical and
      laboratory findings of DHF between infants and children in order to improve
      diagnosis and management of infants with DHF. MATERIAL AND METHOD: A
      retrospective review of hospital charts of DHF patients who were admitted to the
      Children's Hospital between 1995-1999 was carried out. Only confirmed DHF cases,
      either by serologic or virologic studies were included. Clinical and laboratory
      findings were compared using the standard software package SPSS. RESULTS: There
      were 4,595 confirmed dengue patients admitted to the Children's Hospital during
      this 5-year period and among these 245 infants were under one year old (5.3%).
      Unusual presentations of DHF including upper respiratory tract infection (URI)
      symptoms, diarrhea, convulsions and encephalopathy were found more in the infants
      (4.5%, 13.1%, 12.7% and 4.1%) than in the children (1.7%, 2.0%, 2.0% and 0.6%)
      but shock was found less in the infants (25%) than in the children (30.9%). The
      percentages of Tourniquet test positive and low WBC (< or = 5,000 cells/mm3)
      which help in the early diagnosis of dengue were less in the infants (50.2% and
      26.8%) than in the children (92.2% and 71.9%). Liver involvement and/or
      dysfunction were found more in the infants as shown by mean aspartate
      aminotransferase/alanine aminotransferase (AST/ALT) elevation and prolonged
      prothrombin time. Duration of i.v. fluid was shorter in the infants than in the
      children (21.9 vs 38.2 hours). Complications of fluid overload were found more
      often in the infants than in the children (9% vs 3.6%). The case fatality rate
      was 1.2 in the infants and 0.3 in the children. CONCLUSION: Management of infants
      with DHF is critical because early diagnosis is rather difficult and they
      sometimes present with unusual manifestations (convulsions, encephalopathy and
      associated infections). Complications such as hepatic dysfunction and fluid
      overload are more commonly found in infants than in children and adults and also
      the case fatality rate is higher. Judicious i.v. fluid resuscitation and
      replacement is critical to the outcome of infants with DHF. It seems that the
      degree of plasma leakage is less in infants and the duration of plasma leakage is
      shorter in infants than in children.

PMID- 14700167
TI  - Immunobullous diseases in Thai children: report of 24 cases.
AB  - BACKGROUND: Acquired immunobullous diseases in children are very rare and
      difficult to distinguish clinically. OBJECTIVE: To study the clinical
      manifestations, immunopathologic features, treatment and outcome of immunobullous
      diseases in Thai children. MATERIAL AND METHOD: The authors reviewed 24 cases of
      immunobullous diseases in children under 18 years at Queen Sirikit National
      Institute of Child Health from 1983 to 2000. Diagnosis of all cases was made by
      clinical presentations of chronic blistering diseases and confirmed by
      histopathology and immunofluorescent studies. RESULTS: There were 18 cases of
      chronic bullous diseases of childhood (CBDC), 4 cases of bullous pemphigoid (BP)
      and 2 cases of pemphigus vulgaris (PV). The mean age of onset of CBDC and BP were
      4 years and 2 years respectively. There was an equal male to female ratio in both
      CBDC and BP. Both cases of pemphigus (neonate and 4 years old) were female. Most
      CBDC patients (18 cases) responded well to dapsone therapy although 2 cases had
      to be treated with prednisolone simultaneously. All cases with BP were treated
      successfully with prednisolone and dapsone. Neonatal pemphigus was treated
      symptomatically without steroid therapy. The second case of oral pemphigus was
      controlled with low dose prednisolone. CONCLUSION: Immunobullous diseases are
      very rare in children. All patients improved with corticosteroid and/or dapsone
      therapy.

PMID- 14700168
TI  - Congenital tuberculosis.
AB  - This is a retrospective study of congenital tuberculosis in Queen Sirikit
      National Institute of Child Health from 1979 to 1998. There were 9 patients with
      a mean birth weight of 2,500 grams (range 1,800-3,300). The onset of symptoms and
      age of diagnosis ranged from 7 to 42 (mean, 21) days and 14 to 75 (mean, 54) days
      after birth, respectively. The presenting signs and symptoms were fever (100%),
      poor feeding (100%), irritability (100%), failure to gain weight (100%),
      hepatomegaly (100%), splenomegaly (77.8%), cough (88.9%), respiratory distress
      (66.7%) and abdominal distension (77.8%). The tuberculin skin test reaction with
      > or = 10 mm induration was found in 2 of 8 patients. Their abnormal chest
      radiographs revealed bronchopneumonia 66.7 per cent, miliary pattern 33.3 per
      cent and multiple cystic lesion 11.1 per cent. The bacteriological study from
      gastric aspirate content for acid-fast bacilli (AFB) staining and culture were
      positive in 62.5 and 71.4 per cent respectively. Fatality rate was 33.3 per cent
      with no sequele found in the survivors. Congenital tuberculosis is a rare entity
      and difficult to give an early diagnosis. There should be a high index of
      suspicion for tuberculosis in those who had pneumonia and were unresponsive to
      aggressive antibiotics or had unexplained etiology.

PMID- 14700169
TI  - Subacute infective endocarditis caused by Corynebacterium diphtheriae: a case
      report.
AB  - The authors report an 11-year-old boy with septicemia and subacute infective
      endocarditis due to toxigenic-Corynebacterium diphtheriae. The patient had
      underlying congenital heart disease and incomplete immunization. He presented
      with fever, epistaxis and congestive heart failure. He received high-dose
      penicillin therapy and diphtheria antitoxin with clinical improvement. While he
      was receiving a high dose of penicillin for 1 month he developed a generalized
      tonic clonic seizure. A computerized tomogram revealed intracerebral and
      ventricular hemorrhage. Craniotomy with blood clot removal and ventriculostomy
      drainage were done. He died 2 days later from brain death and cardiovascular
      failure.

PMID- 14700170
TI  - Antibody response after measles immunization.
AB  - RATIONALE: Measles is still an important public health problem in Thailand
      despite measles vaccination being practiced since 1984. Vaccine failure is one of
      the suspected reasons for the high incidence of measles. OBJECTIVE: To study the
      seroconversion rate of 9-month-old infants and to study the antibody level in 18
      month-old and 4 year-old children who had measles vaccination at 9 months of age.
      MATERIAL AND METHOD: Enrolled infants and children who attended the child health
      clinic for routine immunization at the Queen Sirikit National Institute of Child
      Health from March 1, 1994 to May 31, 1995. They were divided into 3 groups. Group
      A, 9 month-old infants who came for measles vaccination. Blood samples were drawn
      twice from these infants, before measles vaccination and 3 months later for
      measles antibody level. Group B and C were 18 month-old and 4-year-old children
      who came for their first and second DTP (Diphtheria, Tetanus, Pertussis vaccine)
      booster. One blood sample for measles antibody was drawn from the latter group of
      children. Measles antibody was determined by micro-neutralization technic at the
      National Institute of Health (NIH). The geometric mean antibody titer before and
      after measles vaccination was compared by using the paired t-test. RESULTS: There
      were 30, 31 and 34 infants/children in group A, B and C respectively. No
      significant measles antibody (NT antibody was less than 1:4) was detected in 93.5
      per cent of 9-month-old infants. The seroconversion rate at 3 months after
      vaccination in group A children was 68.75 per cent while in group B, 9 months
      after vaccination it was 53.3 per cent. Ninety seven per cent of children in
      group C had NT antibody above 1:4. The geometric mean titer (GMT) of measles
      antibody in 9-month (before vaccination), 12-month, 18-month infants and 4 year
      old children was 1:2.5; 1:14.8, 1:8.2 and 1:73.8, respectively (p < 0.05).
      CONCLUSION: Almost 70 per cent of vaccinees at 9 months of age had seroconversion
      to measles vaccine with GMT of 1:14.8 while fifty three per cent of 18 month old
      children had an average GMT of 1:8.2. The GMT of the two groups was significantly
      different (p < 0.05). At 4 years of age almost all the children had NT antibody
      to measles with a GMT of 1:73.8 (p < 0.05) Vaccine failure is likely to be one
      factor responsible for the high incidence of measles after the introduction of
      measles vaccine into the Expanded Program of Immunization (EPI). The authors
      suggest giving a booster dose of measles at 15 months of age to boost the
      antibody level before waning of measles antibody at 18 months old, in order to
      protect this group of children from contracting measles.

PMID- 14700171
TI  - Trend of measles morbidity in Thailand.
AB  - RATIONALE: Measles is still an important public health problem in Thailand
      despite the high coverage of measles vaccination since 1984, and the second dose
      of measles vaccination in primary school children in 1991. OBJECTIVE: To study
      the trend of measles morbidity in Thai children. MATERIAL AND METHOD: Review of
      the Annual Epidemiological Surveillance Report of the Epidemiology Section,
      Department of Communicable Disease Control, Ministry of Public Health (MOPH), and
      hospital records of measle cases at the Queen Sirikit National Institute of Child
      Health (QSNICH) (Bangkok Children's Hospital). Paired t-test and analysis of
      variance (ANOVA) were used for data analysis in the present study. RESULTS:
      Before 1984, measles morbidity was very high, at the level of 52.3 to 93.67 per
      100,000 population. After measles vaccine was included in the EPI (Expanded
      Program on Immunization), the morbidity fluctuated for some years, and the group
      of children infected with measles changed from under 5 years to the age group of
      5-9 years old. So a second dose of measles vaccine was added to the EPI given to
      children in Prathom 1 (first year in primary school, 6 years old and over). After
      4 years of adding the second dose of measles in the EPI, measles cases was still
      present in a significant number in both the under 5 and 5-9 age groups. From the
      statistics of measles cases at the QSNICH, with an average of 736 measles cases
      per year, the number of measles cases is now decreasing, but the incidence of
      measles is still high in both the under 5 and 5-9 age groups. CONCLUSION:
      According to the EPI in Thailand, children were given measles vaccine at the age
      of 9 months which is when seroconversion was significantly lower than
      immunization after one year of age. The trend of measles morbidity is decreasing,
      but is still high in children in the under 5 and 5-9 age groups. Vaccine failure
      may be one of the contributing factors of measles cases in children in these age
      groups. A booster dose of measles vaccine at 15-18 months old is suggested in
      order to increase the seroprotection in children in the under 5 and 5-9 age
      groups.

PMID- 14700172
TI  - Medical and non-medical expenses for treating babies born to HIV-infected and non
      HIV-infected mothers.
AB  - BACKGROUND: Most human immunodeficiency virus (HIV) infections among children
      under 5 years are transmitted perinatally. These children require more medical
      attention and hospitalization than non HIV-infected children. The expenses of HIV
      infected children are mostly related to opportunistic infections. OBJECTIVE: To
      compare the medical and non-medical expenses of treating babies born to HIV
      infected and non-HIV-infected mothers at the Queen Sirikit National Institute of
      Child Health (QSNICH). METHODOLOGY: Consecutive children of HIV-infected and non
      HIV-infected mothers born at Rajavithi Hospital, Bangkok, were recruited from
      1993 to 1995. All of them were followed at QSNICH for free medical services. The
      demographic and pregnancy data of mothers and the characteristics of the babies
      of the two groups were compared as well as the number of the hospital visits and
      reported medical and non-medical expenses. RESULTS: 58 children of HIV-infected
      mothers and 119 children of non-HIV-infected mother were recruited during this
      period. Only 30 (51.7%) children of HIV-infected mothers could complete the 18
      month requirement, while 90 (75.6%) of the babies born to non-HIV-infected
      mothers finished the 18 months follow-up period. The two groups did not differ
      much in terms of demographic characteristics, except that the infant fathers were
      younger and serology for syphilis was higher in the HIV-infected mothers. This
      indicated that the HIV-infected mothers had earlier sexual activity. Babies born
      to the HIV-infected mothers tended to have a lower birth weight and were small
      for gestational age (SGA). Nine out of 30 babies (30%) born to the HIV-infected
      mothers were found to be HIV positive at the 18th month of follow-up. The mean
      medical, non-medical, and total expenses of the babies of the infected group were
      2,525.90 +/- 4,328.75, 1,323.07 +/- 1,452.41, 3,848.97 +/- 5,308.90 baht
      respectively, or were 2.4, 2.0, and 2.2 times those of the non-infected group.
      These expenses did not include antiretroviral therapy. CONCLUSION: The total
      medical and non-medical expenses excluding antiretroviral therapy of the children
      of the infected group were 2.2 times those of the non-infected group. Under the
      limitation of financial resource and fast growing health care expenditures, the
      preventive measure for HIV infections including public information, education,
      communication, and condom promotion should be emphasized.

PMID- 14700173
TI  - Technology assessment for management of congenital diaphragmatic hernia:
      immediate versus delayed surgery.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is one of the high-risk
      diseases in pediatric surgery, especially in neonates with symptom presentation
      within 6 hours after birth. Opinion regarding the time of surgery has gradually
      shifted from immediate repair to a policy of stabilization and delayed repair.
      Whether delayed surgery is beneficial remains controversial. OBJECTIVE: To
      evaluate the outcomes regarding whether delayed surgical repair improves survival
      in CDH neonates, who are symptomatic immediately after delivery, is more
      beneficial than immediate surgery. MATERIAL AND METHOD: Data were obtained by
      searching MEDLINE (1966-2002) and the Cochrane Database, Issue 2, 2003 using the
      term "congenital diaphragmatic hernia" and "surgery". Inclusion criteria were
      randomized controlled trial (RCT), prospective trial (PT), retrospective analysis
      (RA) and meta-analysis (MA). Information from the literature was analyzed by the
      computer program of Epi Info Version 3. Statistical significance was reliable at
      the level of p < 0.05. RESULTS: Twenty-five studies were obtained and RCT:RA was
      2:23. Analysis of results of CDH management revealed that pre-operative
      stabilization and delayed surgery improved the survival rate in 14 of 25 in the
      literature (p < 0.05), while the remaining 11 articles showed no statistical
      difference of survival between immediate and delayed surgery (p > 0.05).
      CONCLUSION: From the evidence-based analysis, the results of CDH management
      between immediate versus delayed surgery were unclear. From the reviewer's
      experience at the Queen Sirikit National Institute of Child Health, the strategy
      of pre-operative stabilization and delayed surgery had better improved survival
      of CDH than immediate surgery.

PMID- 14700174
TI  - Scurvy in pediatric patients: a review of 28 cases.
AB  - OBJECTIVE: To study the dietary factors, clinical findings, plasma vitamin C
      level and post-treatment outcome of scurvy in pediatric patients at Queen Sirikit
      National Institute of Child Health. STUDY DESIGN: A retrospective study. METHOD:
      The medical and radiographic records of pediatric patients, diagnosed with scurvy
      at Queen Sirikit National Institute of Child Health from 1995 to 2002 were
      reviewed. RESULTS: Twenty-eight pediatric patients were diagnosed with scurvy.
      Their ages ranged between 10 months-9 years 7 months (median age of 29 months).
      93 per cent of the cases were between 1-4 years of age. All were fed with well
      cooked foods and small amounts or no vegetables and fruits. Supplementation with
      ultra heat temperature (UHT) milk was found in 89 per cent, average 5.8 boxes/day
      and 14.3 months in duration. Eighty-six per cent of cases were misdiagnosed
      previously. Clinical manifestations involved limp or inability to walk (96%),
      tenderness of lower limbs (86%), bleeding per gum (36%), fever (18%), and
      petechial hemorrhage (3.6%). All cases had abnormal radiographic findings
      compatible with scurvy and 2 cases had epiphyseal separation. All had clinical
      improvement within the first week after vitamin C supplementation. CONCLUSION:
      Vitamin C deficiency was found in the children's intake of small amounts or no
      vegetables and fruits together with UHT-milk. Frequent manifestations were
      limping and inability to walk and pain in the lower limbs. Response to vitamin C
      treatment was dramatic.

PMID- 14700175
TI  - Can octreotide be the first line treatment for chylothorax?
AB  - BACKGROUND: Chylothorax is a rare but serious condition with a high rate of
      morbidity that may lead to death. It may be spontaneous or a complication of
      cardiac surgery. Treatment of this potentially harmful condition is not well
      established and may comprise dietary interventions. In order to avoid surgery,
      somatostatin and octreotide have been recently suggested as new modalities for
      the treatment of chylothorax. OBJECTIVE: To study the efficacy of octreotide for
      the treatment of chylothorax. METHOD: Cases reports. RESULT: The authors report
      two cases of chylothorax successfully treated with intravenous infusion of
      octreotide as an adjunct to conventional treatment. Furthermore, the authors
      report their last case who were treated successfully with octreotide as the first
      line drug without diet modification. CONCLUSION: It seems that octreotide is
      effective, noninvasive and safe. It can be used as an optional or first line
      treatment for chylothorax.

PMID- 14700176
TI  - Evidence-based practice for neonatal nursing.

PMID- 14700177
TI  - Physiologic effects of CPAP: application and monitoring.
AB  - Although a wide array of respiratory care modalities has been employed to manage
      neonatal respiratory distress syndrome (RDS), the recent focus has emphasized
      strategies that correct lung pathophysiology while protecting the lung from
      further insult. Continuous positive airway pressure (CPAP) has remained a viable
      option for NICU infants since its introduction in 1971. Current methods of
      monitoring allow clinicians to troubleshoot and better understand the physiologic
      and clinical impact of administering CPAP to neonates with RDS. This article
      highlights the renewed interest in CPAP therapy and current methods of
      monitoring.

PMID- 14700178
TI  - Outcomes of developmental care in an Australian neonatal intensive care nursery.
AB  - OBJECTIVE: To evaluate the outcomes of implementation of a developmental care
      model in an Australian tertiary NICU. STUDY DESIGN: A retrospective chart audit
      was used to determine the differences between predevelopmental and developmental
      care outcomes for infants, parents, the unit, and nursing. SAMPLE: Two subsets of
      infants were selected for comparison: one of infants receiving predevelopmental
      care (n = 42) and another of infants receiving developmental care (n = 42).
      RESULTS: Infants receiving developmental care required less time on total
      parenteral nutrition, required less exogenous surfactant, and had less documented
      feeding intolerance. Changes were observed in ambience and in the use of space
      for providing parent-infant care. Also observed was the individualized expertise
      of nursing staff and of parents.

PMID- 14700179
TI  - Swedish men's experiences of becoming fathers to their preterm infants.
AB  - PURPOSE: To describe Swedish men's experiences of becoming fathers to their
      preterm infants. DESIGN: A cross-sectional descriptive study. SAMPLE AND METHOD:
      Eight men participated in semistructured interviews with open-ended questions.
      The interviews were analyzed using manifest and latent content analysis. MAIN
      OUTCOME VARIABLES: The concepts of control and noncontrol. RESULT: The manifest
      analysis of the interview text produced six categories: concern, stress,
      helplessness, security, support, and happiness. The latent content interpretation
      indicated that the concepts of control and noncontrol were relevant to the
      fathers' experiences. The men's experiences of early fatherhood were influenced
      by their ability to experience control. When concern, stress, and helplessness
      dominated the fathers' experiences and coincided with low levels of happiness,
      support, and security, they experienced noncontrol. Conversely, when they
      experienced support, security, and happiness, they felt that they were in control
      and able to handle the situation.

PMID- 14700180
TI  - Kangaroo (skin-to-skin) care with a preterm infant before, during, and after
      mechanical ventilation.
AB  - Using kangaroo care (KC) with unstable and/or ventilated infants remains
      controversial. In this article, potential advantages for ventilated infants and
      their mothers are discussed. The 33-week-gestation infant in this case study
      presented with mild respiratory distress at birth, requiring supplemental oxygen
      at hour 2. With no improvement by hour 18, KC was also begun, first for 1.25
      hours and then, 2 hours later, for 3.5 hours. The infant was intubated at hour 45
      for increasing respiratory distress, and KC resumed 24 hours later for 1 hour and
      3 hours after that for an additional 3 hours. Extubation occurred at hour 90.
      Kangaroo care resumed 2 hours later for periods of 1.5, 1.5, and 1 hour over the
      next 8 hours, 2.5 hours more later that day (day 5, the last day of data
      collection). Thereafter, KC was done intermittently until discharge on day 9.
      Total KC times for pre-vent, vent, and immediate post-vent periods were 4.75, 4,
      and 6.5 hours, respectively. The data from this study suggest that KC may assist
      in, rather than retard, recovery from respiratory distress. KC may also foster
      maternal relaxation and minimize maternal stress.

PMID- 14700181
TI  - Antibiotic resistance: is the end of an era near?

PMID- 14700182
TI  - Neonatal malignancies.

PMID- 14700183
TI  - Legal issues in neonatal nursing.

PMID- 14700184
TI  - Myths and facts about pain in neonates.

PMID- 14700185
TI  - A Christmas story.

PMID- 14700186
TI  - RAPD method useful for distinguishing Leishmania species: design of specific
      primers for L. braziliensis.
AB  - The technique of Random Amplification Polymorphic DNA allows fragments of the
      genome to be amplified by means of polymerase chain reaction (PCR) without
      previous knowledge of their sequences. The protozoa of the genus Leishmania
      present great genetic variability, making it difficult to characterize the
      different species. A method is developed with a single 10-mers long primer, which
      allows the species L. braziliensis, L. mexicana, L. infantum, L. tropica, L.
      chagasi, L. amazonensis and L. major to be differentiated. These products
      amplified by RAPD have also facilitated the design of some primers that amplify
      L. braziliensis DNA exclusively.

PMID- 14700187
TI  - P19: a female and tissue specifically expressed gene in Schistosoma mansoni,
      regulated by pairing with the male.
AB  - A female-specific sequence was isolated from a cDNA library of Schistosoma
      mansoni and further characterized. Expression of the corresponding gene (p19)
      depends on pairing with a male. In situ hybridization and immunohistology
      experiments revealed exclusive expression of the gene in the cells of the
      vitellarium, suggesting a function in egg formation. In addition, experimental
      evidence for cross-linking of the protein under oxidative conditions supports the
      assumption that the p19 gene may code for an egg-shell precursor protein.

PMID- 14700188
TI  - The influence of sampling effort and the performance of the Kato-Katz technique
      in diagnosing Schistosoma mansoni and hookworm co-infections in rural Cote
      d'Ivoire.
AB  - The Klato-Katz method is widely used for diagnosing helminth infections in
      epidemiological surveys, but is known to have a low sensitivity. In the case of
      Schistosoma mansoni, statistical methods have been developed to compensate for
      the poor sensitivity, but the same is not true of any other helminth parasite, or
      infections with multiple-helminth species. We screened 101 schoolchildren from a
      rural area of Cote d'Ivoire over 5 consecutive days and made 5 Kato-Katz readings
      from each stool specimen. We estimated single and dual-species infections with S.
      mansoni and hookworm based on raw egg count data and after developing a latent
      class model. The cumulative prevalence of co-infections was estimated at 9.9%
      after reading slides on the first day, and 57.0% after reading all 25 slides per
      person. The latent class model yielded a co-infection prevalence estimate of
      79.6%, with marginal prevalence estimates for hookworm and S. mansoni infections
      of 83.9% and 91.6% respectively. The sensitivities of a single Kato-Katz thick
      smear for detection of S. mansoni alone, hookworms alone, or S. mansoni plus
      hookworms were 22.4%, 8.0% and 17.7%, respectively. In the current setting this
      could be attributable to low infection intensities of both parasites, combined
      with intra-specimen and day-to-day variation in egg output. If confirmed in other
      settings, these findings have implications for estimating the prevalence of
      multiple species helminth infections, and hence the design and implementation of
      efficacious and cost-effective control programmes.

PMID- 14700189
TI  - Schistosoma mansoni and Echinostoma caproni excretory-secretory products
      differentially affect gene expression in Biomphalaria glabrata embryonic cells.
AB  - Biomphalaria glabrata embryonic (Bge) cells have been shown to be a valuable in
      vitro cellular model for the study of snail host-parasite interactions. They both
      promote the growth and differentiation of various trematode species including
      Schistosoma mansoni, and Echinostoma caproni and share some morphological and
      functional features with circulating haemocytes. As an approach to investigate
      snail genes potentially regulated following exposure to trematode excretory
      secretory (ES) products, we compared gene expression profiles of Bge cells
      exposed to saline solution, or saline solution containing ES products from S.
      mansoni or E. caproni, two trematode species parasitizing B. glabrata. Following
      differential display RT-PCR analysis we characterized 23 differentially displayed
      cDNAs and we focussed on the 5 cDNAs showing sequence similarity to known genes
      for expression validation. Using RT-PCR, we confirmed that ES products from S.
      mansoni and E. caproni differentially affect the expression levels of 4 out of
      the 5 transcripts. These partial transcripts corresponded to novel B. glabrata
      sequences, and showed significant sequence similarity to genes coding for (i)
      cytochrome C, (ii) methyl-binding proteins, (iii) glutamine synthetases, and (iv)
      protease inhibitors from the Kunitz family. The possible significance of these
      gene expression changes in host-parasite molecular interactions is discussed.

PMID- 14700190
TI  - Changes in adenosine transport associated with melaminophenyl arsenical (Mel CY)
      resistance in Trypanosoma evansi: down-regulation and affinity changes of the P2
      transporter.
AB  - Studies of the kinetics of adenosine transport were carried out on the P1 and P2
      transporters of drug-sensitive Trypanosoma evansi and its cloned derivative,
      resistant to the melaminophenyl arsenical Mel CY. Characterization of adenosine
      uptake was made by estimation of the maximum concentration taken up at time
      infinity (Amax). Amax on the P2 transporter of sensitive T. evansi was greater
      than Amax on the P1 transporter. Amax of the P2 transporter was significantly
      decreased in drug-resistant trypanosomes. The effect of adenosine concentration
      and inhibitors, on the rate of adenosine uptake, was described by Michaelis
      Menten equations. In sensitive T. evansi, the maximum velocity of adenosine
      uptake (Vmax) of the P2 transporter was 2-fold greater than Vmax of the P1
      transporter. The Vmax of the P2 transporter in resistant parasites was reduced 9
      fold. The binding constants Km and Ki on the P2 transporter of resistant T.
      evansi, showed that resistance was associated with an increased affinity for
      adenosine, and a decreased affinity for adenine and Berenil. We suggest that
      resistance to melaminophenyl arsenicals in T. evansi, occurs via 2 mechanisms:
      (1) a reduction in the number of expressed P2 transporter molecules resulting in
      decreased uptake of melaminophenyl arsenicals; (2) a change in the binding
      properties of the P2 transporter.

PMID- 14700191
TI  - Cortisol influences the host-parasite interaction between the rainbow trout
      (Oncorhynchus mykiss) and the crustacean ectoparasite Argulus japonicus.
AB  - The host-parasite interaction between the rainbow trout Oncorhynchus mykiss and
      the fish louse Argulus japonicus was investigated by administering low levels of
      dietary cortisol before infecting the fish with low numbers of the parasite.
      After 24 h, the dietary cortisol treatment elevated blood cortisol and glucose
      levels and stimulated the synthesis of secretory granules in the upper layer of
      skin cells. Infection with 6 lice per fish caused skin infiltration by
      lymphocytes, also in areas without parasites. The lymphocyte numbers in the blood
      at 48 h post-parasite infection were reduced. Other changes, typical for exposure
      to many stressors and mediated by cortisol, were also found in the epidermis of
      parasitized fish, although neither plasma cortisol nor glucose levels were
      noticeably affected. Glucocorticoid receptors were localized
      immunohistochemically and found in the upper epidermal layer of pavement and
      filament cells, and in the leucocytes migrating in these layers. Cortisol-fed
      fish had reduced numbers of parasites and the changes in the host skin are likely
      involved in this reduction. Thus a mild cortisol stress response might be
      adaptive in rejecting these parasites. Further, the data suggest that this effect
      of cortisol is mediated by the glucocorticoid receptor in the skin epidermis, as
      these are located directly at the site of parasite attachment and feeding in the
      upper skin cells that produce more secretory granules in response to cortisol
      feeding.

PMID- 14700192
TI  - Invasion of the shovelnose ray (Rhinobatos typus) by Neoheterocotyle rhinobatidis
      and Merizocotyle icopae (Monogenea: Monocotylidae).
AB  - This study examined the route of infection by free-swimming larvae of 2
      monocotylid monogeneans that inhabit the gills (Neoheterocotyle rhinobatidis) and
      the nasal tissue (Merizocotyle icopae) of the shovelnose ray, Rhinobatos typus,
      from Heron Island on the Great Barrier Reef, Australia. Larvae of N. rhinobatidis
      and M. icopae attached directly to the gills and the nasal tissue of the ray,
      respectively, and did not first settle on the skin. Initial development of the
      post-oncomiracidium of N. rhinobatidis was rapid and hamuli formed between 6 and
      24 h p.i. at a mean temperature of 26 degrees C. However, growth then slowed
      markedly and was variable; only 2 fully mature individuals were found 20 days
      p.i. at a mean temperature of 24.5 degrees C. Development of M. icopae was slow
      and variable throughout; hamuli did not appear until 10 days p.i. and no mature
      individuals were obtained even 22 days p.i. at a mean temperature of 24.5 degrees
      C. No character could be found as an indicator of parasite age for N.
      rhinobatidis or M. icopae due to the high variability in development in both
      species.

PMID- 14700193
TI  - Differential phenoloxidase activity between native and invasive gammarids
      infected by local acanthocephalans: differential immunosuppression?
AB  - Manipulative endoparasites can alter the behaviour and the physiology of their
      intermediate hosts in ways that increase the probability of successful
      transmission to the final host. This requires that the parasite is able to
      circumvent its host's immune defence. Successful immune evasion may depend on
      host-parasite coevolutionary history and the appearance of new hosts invading the
      local host population may promote local parasite maladaptation. To test this
      hypothesis, we examined the effect of 2 acanthocephalan parasites, Pomphorhynchus
      laevis and Polymorphus minutus, on the immunity of their local and new invasive
      gammarid intermediate hosts, respectively Gammarus pulex and Gammarus roeseli. We
      found that infection by each parasite was correlated with a decrease, at
      different degrees, of the standing level of immune defence in local hosts-
      measured as the phenoloxidase (PO) enzyme activity--whereas invasive hosts
      infected by P. laevis had their PO-enzyme activity enhanced. These results
      suggest that these acanthocephalans evade their local host immune response
      through immunosuppression but cannot evade the immune response of their new
      invasive host. The potential role of this maladaptation on the success of
      invasive species is discussed.

PMID- 14700194
TI  - Cloning two full-length beta-tubulin isotype cDNAs from Cooperia oncophora, and
      screening for benzimidazole resistance-associated mutations in two isolates.
AB  - Two full-length beta-tubulin cDNAs, representing isotypes 1 and 2, were cloned
      from the cattle nematode Cooperia oncophora. The predicted protein sequences span
      448 amino acids, and show a high degree of identity to beta-tubulins from other
      nematodes. While C. oncophora isotype 1 sequence had the highest identity to
      Haemonchus contortus isotype 1 and Teladorsagia circumcincta sequences (95%
      identity), the C. oncophora isotype 2 sequence was most similar to H. contortus
      isotype 2 and Trichostrongylus colubriformis (92% identity). Alignment of the two
      C. oncophora sequences with other trichostrongylid beta-tubulins deposited in
      GenBank showed a clear distinction between isotype 1 and 2 beta-tubulin classes.
      The two classes differed at 19 amino acid positions, most notably at the carboxy
      terminus. These isotype-defining residues were conserved among different
      trichostrongylid species within a class. Analysis of fragments of both genes
      revealed a high degree of genetic variability in coding and non-coding regions.
      However, all nucleotide differences detected in the coding region were silent, as
      they did not result in any amino acid substitution. Analysis of 2 groups of worms
      for the codon 200 polymorphism associated with benzimidazole resistance revealed
      a proportion of worms in 1 of the groups bearing a tyrosine at this position.

PMID- 14700195
TI  - Fossil evidence of phorid parasitism (Diptera: Phoridae) by allantonematid
      nematodes (Tylenchida: Allantonematidae).
AB  - Howardula helenoschini sp. n. (Tylenchida: Allantonematidae) is described from 40
      million year-old Baltic amber. The nematodes are parasitic in the body cavity of
      an adult fly of the genus Triphleba (Phoridae: Diptera). Characteristics of the
      fossil species are the large size of the pre-adult juveniles and a small number
      of progeny compared with extant Howardula parasites of flies. Reasons are given
      why these features suggest that this species was at an early stage of adapting,
      evolutionarily, to its insect host.

PMID- 14700196
TI  - Population dynamics of Toxocara canis in pigs receiving a single or multiple
      infection.
AB  - The population dynamics of Toxocara canis in pigs, and their immune response to a
      primary and a challenge infection, were studied by parasitological,
      haematological and serological parameters. Seventy pigs were divided into 4
      groups; 35 pigs received a primary infection (group A), 15 pigs received both a
      primary and a challenge infection (group B), 15 pigs received the challenge
      infection only (group C), and 5 pigs served as helminth-free controls (group NC).
      A dose of 50,000 eggs was administered for the primary infection (day 0) and a
      dose of 10,000 eggs was given for the challenge infection (day 28). On days 7,
      14, 21 and 28 p.i., 5 pigs of group A, and on days 35, 42 and 49 p.i., 5 pigs
      from each of groups A, B and C were necropsied. Numbers of recovered larvae
      varied widely among the 5 pigs of each group on all days of necropsy. Toxocara
      canis larvae were recovered predominantly from the lungs; migration of larvae to
      other organs or tissues from the lungs was restricted. In group A, the larval
      burden in the lungs peaked on day 14 p.i., and the larval densities decreased
      significantly over time. Thereafter, the majority of larvae were recovered from
      the lungs until the end of the experiment (day 49 p.i.). A few larvae were found
      in the muscles and brain until day 42 p.i., and 2 larvae were found in the eyes
      of 2 pigs on day 35 p.i. There was little evidence of protective immunity to a
      challenge infection in this experiment. The eosinophil levels tended not to
      increase in pigs receiving a challenge infection, in contrast to the challenge
      control pigs. The fact that T. canis larvae migrate and persist in the tissues of
      pigs for more than 1 month suggests a zoonotic risk in infected pigs. The
      relevance of these data to the population biology and immunology of porcine and
      human toxocarosis is discussed.

PMID- 14700197
TI  - Molecular phylogenetic analysis of the genus Gyrodactylus (Platyhelminthes:
      Monogenea) inferred from rDNA ITS region: subgenera versus species groups.
AB  - Analyses of small subunit ribosomal RNA gene sequences of representatives of
      major taxa of Monopisthocotylea were performed to identify the sister group of
      Gyrodactylus. Nuclear ribosomal DNA sequences from the complete internal
      transcribed spacer (ITS) region were used to infer phylogeny of 37 Gyrodactylus
      species and Gyrodactyloides bychowskii, Macrogyrodactylus polypteri and
      Gyrdicotylus gallieni, using maximum likelihood, parsimony and Bayesian
      inference. The genus Gyrodactylus appeared to be a monophyletic group in all
      analyses, based on the present data set. Within the genus, there were 3 major
      groups recognized by high bootstrap values and posterior probabilities. None of
      the 6 subgenera appeared to be monophyletic, and the most basal subgenus G.
      (Gyrodactylus) was paraphyletic. Characteristics of the excretory system of
      Gyrodactylus do not seem to be conservative enough to reveal subgenera within
      Gyrodactylus and we suggest abandoning existing subgenera as indicators of
      phylogeny. The grouping of species based on the morphology of the ventral bar and
      marginal hooks seems to have sufficient power to infer relationships between the
      Gyrodactylus species.

PMID- 14700198
TI  - Antimycobacterial natural products.
AB  - This review covers the literature published between January 1990 and December
      2002 (inclusive) for natural products with reported antimycobacterial activity,
      with 248 citations to 352 compounds isolated from both terrestrial and marine
      sources The compounds are presented in order of chemical type, namely
      lipids/fatty acids and simple aromatics phenolics and acetogenic quinones,
      peptides, alkaloids, terpenes (monoterpenoids, diterpenes, sesquiterpenes,
      sesterterpenes and triterpenes) and steroids.

PMID- 14700199
TI  - Combretastatins: from natural products to drug discovery.
AB  - The combretastatins are a group of anti-mitotic agents isolated from the bark of
      the South African tree Combretum caffrum. The most potent member is
      combretastatin A-4, and this compound together with a phosphate pro-drug form
      have already progressed through into clinical trails for the treatment of solid
      tumours. What makes this class of compounds rather more interesting than other
      anti-mitotic agents is that they are also angiogenesis inhibitors, and are being
      evaluated for their efficacy in the treatment of diabetic retinopathy which is
      the biggest single cause of blindness They are thus of considerable contemporary
      interest.

PMID- 14700200
TI  - Naturally occurring aristolactams, aristolochic acids and dioxoaporphines and
      their biological activities.
AB  - Aristolactams, having a phenanthrene chromophore are a small group of compounds
      mainly found in the Aristolochiaceae together with the aristolochic acids and 4,5
      dioxoaporphines. In this report, these three important classes of natural
      products are reviewed and classified on the basis of their oxygenation pattern.
      In addition the biological activities of these compounds and their general
      chemistry are discussed.

PMID- 14700201
TI  - Muscarine, imidazole, oxazole, and thiazole alkaloids.
AB  - The occurrence, structure determination, biological activities, as well as total
      syntheses of muscarine, imidazole, oxazole and thiazole alkaloids have been
      reviewed. The literature covers from the middle of 2001 to the end of 2002, and
      149 references are cited.

PMID- 14700202
TI  - Amaryllidaceae and Sceletium alkaloids.
AB  - This review covers the isolation, biological activity and chemical synthesis of
      Amaryllidaceae alkaloids and the structurally related Sceletium alkaloids. The
      literature from July 2001 to the end of 2002 is reviewed, and 61 references are
      cited.

PMID- 14700203
TI  - Pigments of fungi (Macromycetes).
AB  - This review summarises progress reported in the chemical, biological and
      mycological literature dealing with the isolation, characterisation and chemistry
      of pigments manufactured by those fungi that produce conspicuous fruit bodies
      (Macromycetes). Work that has appeared in the primary literature between
      September 1998 and May 2003 is covered, and 99 references are cited.

PMID- 14700204
TI  - Triterpenoids.
AB  - This review covers the isolation and structure determination of triterpenoids
      including squalene derivatives, lanostanes, cycloartanes, dammaranes, euphanes,
      tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleananes,
      friedelanes, ursanes, hopanes, fernanes, sipholanes, isomalabaricanes, serratanes
      and saponins The literature from January to December 2001 is reviewed and 242
      references are cited.

PMID- 14700205
TI  - How to improve hospital-physician relationships.
AB  - For healthcare organizations (HCOs), successfully partnering with physicians is
      the strategic imperative. A number of misperceptions and limiting beliefs
      compromise partnering initiatives. To pursue a more successful approach to
      partnering, it is important to understand some of the forces that are affecting
      the healthcare industry. The accelerating pace of change demands that healthcare
      leaders serve as change agents, evoking resentment from the majority of
      healthcare stakeholders. Demands for measured accountability and the shift of
      control from provider to consumer threaten the physician perception as "captain
      of the ship." Cultural differences between the expert culture of physicians and
      the affiliative culture of the HCO perpetuate feelings of distrust and compromise
      efforts to actualize interdependencies. Economic pressures and an unwillingness
      to make time to engage in dialog prevent the provider community from serving as a
      creative force in shaping its own future and restrict the ability to build the
      mutual trust that is necessary for the establishment of successful relationships.
      Measures that would enhance the likelihood of forming successful and lasting
      relationships include the following. Adopting an orchestration model would allow
      a flexible way to bring services to a community. It may be the only way to
      simultaneously integrate and specialize. Budgeting to reflect service-line
      functioning would allow the systematic integration of patient care throughput and
      provide a necessary metric for assessing clinical and operational performance.
      Segmenting the medical staff would allow the establishment of pluralistic
      relationships based on shared goals and values and allow change agents to lead to
      critical mass rather than consensus. Focusing on the customer would ensure
      relevance in the changing medical marketplace. Adopting a complexity science
      metaphor rather than continuing in a command-and-control, top-down organizational
      structure would enhance adaptability and help maximize human capital. Most
      importantly, forming relationships that center around shared purpose and values
      will lay the foundation for excellence and sustainability while restoring a sense
      of meaning, pride, and joy to the healthcare professions.

PMID- 14700206
TI  - Restructuring hospital-physician relationships for future success.
AB  - Integrating physicians into the Healthfirst administration through employment
      sowed seeds of mutual understanding among these two groups that would benefit the
      system immeasurably over the next several years. The immediate future, however,
      saw only cultural upheaval between our hospitals and newly employed physicians,
      hospitals and nonemployed physicians, employed and nonemployed physicians, as
      well as specialists and primary care providers. Traditional physician
      relationship-building efforts became difficult, if not impossible, to maintain.
      Essentially, administration was forced to scrap ten years of physician
      development plans in order to reconfigure a relations effort that would maintain
      hospital support from all sides while restructuring the employed medical group.
      This article describes the evolution of Healthfirst's approach to maintaining
      effective physician relationships within our healthcare system and its affiliated
      entities over the past decade. Specifically, the article details the manner in
      which our system has evolved physician-relations activity to maintain an
      effective strategy during times of significant change in the healthcare industry.

PMID- 14700207
TI  - Hospital-physician relations--a response.

PMID- 14700208
TI  - Hospital-physician relationships: a synergy that must work.

PMID- 14700209
TI  - Building hospital-physician relationships through servant leadership.

PMID- 14700210
TI  - Human currency, Part II: Defining the problem.

PMID- 14700211
TI  - What is your diagnosis? Monilethrix.

PMID- 14700212
TI  - Crohn's disease of the penis masquerading as pyoderma gangrenosum: a case report
      and review of the literature.
AB  - Both pyoderma gangrenosum (PG) and cutaneous (metastatic) Crohn's disease (CCD)
      may occur in the setting of inflammatory bowel disease (IBD). Clinical
      distinction between PG and CCD may be difficult because clinical and pathologic
      features often are similar. Although surgical debridement is therapeutic in CCD,
      it may lead to increased tissue loss and disease progression (pathergy) in PG.
      Thus, it is important to determine a definitive diagnosis before surgical
      debridement, especially in tissue-sensitive sites. We present a patient with
      chronic ulceration of the penis who ultimately was diagnosed with CCD following
      an initial misdiagnosis of PG.

PMID- 14700213
TI  - Cutaneous histoplasmosis in patients with acquired immunodeficiency syndrome.
AB  - Since 1987, the US Centers for Disease Control and Prevention has considered
      disseminated histoplasmosis an acquired immunodeficiency syndrome (AIDS)-defining
      illness. Cutaneous manifestations of disseminated disease are diverse and often
      present as a nondescript rash with systemic complaints. Diagnosis is best
      established by histopathologic examination with appropriate stains for fungal
      organisms. Skin lesions often resolve within weeks of initiating treatment. We
      detail a case of cutaneous histoplasmosis and review its epidemiology, common
      presentations, diagnosis, and treatment options.

PMID- 14700214
TI  - The nature of solar keratosis.

PMID- 14700215
TI  - The nature of solar keratosis.

PMID- 14700216
TI  - Keratosis punctata of the instep.
AB  - We present a case of keratosis punctata involving the instep of both feet in
      addition to palmar and plantar creases, a finding not previously reported to our
      knowledge. We also discuss a closely related entity, keratosis punctata palmaris
      et plantaris (KPPP), and why we believe our case does not simply represent a
      variant of keratosis punctata of the palmar creases (KPPC).

PMID- 14700217
TI  - Cumulative irritancy potential of adapalene cream 0.1% compared with adapalene
      gel 0.1% and several tretinoin formulations.
AB  - Thirty-one subjects (8 males and 23 females; mean age, 49.8 years) were enrolled
      in a single-center study to assess the irritancy potential of adapalene (Differin
      cream 0.1% and Differin gel 0.1%) and tretinoin (Avita cream 0.025%, Retin-A
      cream 0.025%, Retin-A cream 0.05%, Retin-A Micro gel 0.1%, and generic cream
      0.025%) as compared with white petrolatum when applied under occlusive
      conditions. All test materials were applied randomly under occlusion to sites
      located on the upper area of the subject's back under protective patches. All
      patches were applied to the same sites unless the degree of reaction to a test
      product or the adhesive necessitated removal (grade 3). Each test material was
      applied daily, Monday through Friday, for approximately 24 hours, with the Friday
      patches left in place over the weekend. Twenty-six of the 31 subjects (84%)
      completed the study. No subject discontinued because of an adverse event. Five
      subjects voluntarily discontinued the study early for reasons unrelated to study
      treatment (4 subject request and 1 lost to follow-up). In the statistical
      comparison of the 7 test products, the mean cumulative irritancy index of both
      adapalene cream 0.1% and gel 0.1% was statistically significantly (P<.05) lower
      than for all of the tretinoin products used and was not significantly higher than
      the negative control product (white petrolatum).

PMID- 14700218
TI  - Use of the word rash.

PMID- 14700219
TI  - Meteorites, Mars and Beagle 2--from novel analysis in the laboratory to
      pioneering experiments in space.
AB  - On 25 December 2003, the British-built Beagle 2 probe will land on the surface of
      Mars to carry out one of the most potentially important pieces of analytical
      science ever conceived: to search for evidence of extra terrestrial life. Dr Ian
      Wright of the Open University talks us through the difficulties of performing
      measurements in such a harsh environment.

PMID- 14700220
TI  - Fuzzy logic applications.
AB  - Fuzzy logic is a modeling method well suited for the control of complex and non
      linear systems. This paper illustrates some of the power of fuzzy logic through a
      simple control example. For the analytical chemist, fuzzy logic incorporates
      imprecision from measurement noise as well as from linguistic process
      descriptions to produce operational control systems.

PMID- 14700221
TI  - Stellan Hjerten, Uppsala University.

PMID- 14700222
TI  - Optimisation of partial least squares regression calibration models in near
      infrared spectroscopy: a novel algorithm for wavelength selection.
AB  - A novel optimisation algorithm is presented for full spectrum calibration models
      in near-infrared (NIR) spectroscopy. The algorithm is used to investigate the
      affect of removing continuous spectral regions on parameters critical to the
      validity of the model (e.g. explained variance, bias etc.) and ultimately
      identify and remove problem areas of the spectrum. As an example of its
      application, this paper shows how to optimise partial least squares regression
      (PLSR) calibration models for predicting moisture content within an intact
      pharmaceutical product and how problems due to changes in the nature of samples
      since setting up the original model may be eliminated. On application of two
      validated calibration models to a new set of samples unacceptable results were
      obtained for bias (-0.26 and -0.21% m/m moisture content) between the NIR
      predicted values and the true values (Karl Fischer analysis). The optimisation
      algorithm identified small regions of the spectrum, which if included in
      development of the models contributed significant bias to the final prediction.
      On removal of these problem regions the calibration models were found to be
      equally accurate and precise, but with the added advantage of robustness to a
      variable region of the sample spectrum (bias reduced to -0.05 and -0.09% m/m).

PMID- 14700223
TI  - Chemometric resolution of ATR-IR spectra data for polycondensation reaction of
      bis(hydroxyethylterephthalate) with a combination of self-modeling curve
      resolution (SMCR) and local rank analysis.
AB  - Self-modeling curve resolution (SMCR) methods, simple-to-use interactive self
      modeling mixture analysis (SIMPLISMA) and alternating least squares (ALS) were
      used to calculate pure concentration profiles and pure spectra for the two-way
      spectral data collected during the on-line polycondensation reaction of
      bis(hydroxyethylterephthalate) with an ATR-FT-IR spectrometer. In order to
      improve the resolution results, SIMPLISMA was combined with local rank analysis
      method, fixed size moving window evolving factor analysis (FSMWEFA) to search for
      selective regions of various components and then look for the purest wavenumber
      variables in the selective regions. Such combination allows more accurate
      determination of the number of chemical components in the reaction system and the
      calculations of more accurate concentration profiles and spectra.

PMID- 14700224
TI  - Measurement of the percentage volume particle size distribution of powdered
      microcrystalline cellulose using reflectance near-infrared spectroscopy.
AB  - This is the first reported method for determining the percentage volume particle
      size distribution of a powder (microcrystalline cellulose) by near-infrared (NIR)
      reflectance spectroscopy. A total of 113 samples of powdered microcrystalline
      cellulose were used from six different commercially available grades, with
      different moisture contents (range: 0.9-4.8% m/m). NIR reflectance measurements
      of these samples were made in narrow soda glass vials. Reference particle size
      data for the samples were acquired by laser diffraction. The NIR data were then
      calibrated to measure particle size by partial least squares regression. The
      effects of a range of different NIR data pre-treatments on calibration and
      prediction precision were investigated. Overall, simple absorbance data were
      found to produce regression models with the best predictive ability (root mean
      square error of prediction = 0.90%). The method was also found to be insensitive
      to moisture content.

PMID- 14700225
TI  - Tracking the distribution of "ecstasy" tablets by Raman composition profiling: a
      large scale feasibility study.
AB  - Here we report the results of the largest study yet carried out on composition
      profiling of seized "ecstasy" tablets by Raman spectroscopy. Approximately 1500
      tablets from different seizures in N. Ireland were analysed and even though
      practically all the tablets contained MDMA as active constituent, there were very
      significant differences in their Raman spectra, which were due to variations in
      both the nature and concentration of the excipients used and/or the degree of
      hydration of the MDMA. The ratios of the peak heights of the prominent drug bands
      at 810 cm(-1) and 716 cm(-1) (which vary with hydration state of the drug), and
      the drug band at 810 cm(-1) against the largest clearly discernible excipient
      band in the spectrum were measured for all the samples. It was found that there
      was sufficient variation in composition in the general sample population to make
      any matches between batches of tablets taken from different seizures significant,
      rather than the result of random chance. Despite the large number of different
      batches of tablets examined in this study, only two examples of indistinguishable
      sets of tablets were found and in only one of these had the two batches of
      tablets been seized at different times. Finally, the fact that there are many
      examples of batches of tablets (particularly in different batches taken from
      single seizures) in which the differences between each set are sufficiently small
      that they appear to arise only from random variations within a standard
      manufacturing method implies that, with more extensive data, it may be possible
      to recognize the "signature" of tablets prepared by major manufacturers.

PMID- 14700226
TI  - A non-invasive analysis method for on-chip spectrophotometric detection using
      liquid-core waveguiding within a 3D architecture.
AB  - The on-chip measurement of absorbing species has proven to be challenging,
      particularly with respect to the sample pathlengths available in a miniaturised
      system. This paper demonstrates how the principles of total internal reflection
      can be utilised to form a liquid-core waveguide along a single microfluidic
      channel, increasing the sampling pathlength to 5 mm while maintaining a detection
      volume of < or = 1 microL. This was achieved using the Teflon fluoropolymers
      PTFE, FEP and AF as cladding for the liquid-core waveguide. In conjunction with a
      3D chip architecture, the use of the liquid-core waveguide enables more efficient
      use of the probing light beam along with easy and effective coupling of the
      source, microfluidic chip and the detection system. The confirmation that
      waveguiding was occurring was successfully demonstrated and the subsequent
      spectrophotometric analysis of crystal violet provided a linear calibration with
      reproducibility (< 2.4% RSD) and limits of detection (< 1.3 microM), comparable
      to absorbance measurements made with a standard UV-Vis spectrophotometer.

PMID- 14700227
TI  - The impact of column inner diameter on chromatographic performance in temperature
      gradient liquid chromatography.
AB  - The impact of column inner diameter on chromatographic performance in temperature
      gradient liquid chromatography has been investigated in the present study.
      Columns with inner diameters of 0.32, 0.53, 3.2 and 4.6 mm were compared with
      respect to retention and efficiency characteristics using temperature gradients
      from 30 to 90 degrees C with temperature ramps of 1, 5, 10 and 20 degrees C min(
      1). The columns were all of 15 cm length and were packed with 3 microm Hypersil
      ODS particles. Alkylbenzenes served as model compounds, and the mobile phase
      consisted of acetonitrile-water (50:50, v/v). The study revealed that the column
      ID is not a critical limiting factor when performing temperature programming in
      LC, at least for columns narrower than 4.6 mm inner diameter in the temperature
      interval 30-90 degrees C. The retention times for all components on all columns
      were highly comparable, with similar peak profiles without any signs of peak
      splitting. The use of mobile phase pre-heating when using the larger bore columns
      was avoided by starting the temperature gradients close to ambient. However, the
      relative apparent efficiency was inversely proportional to column inner diameter,
      making the capillary columns generally more functional towards temperature
      gradients than the larger bore columns with respect to chromatographic
      efficiency. In addition, the capillary columns possessed higher robustness
      towards temperature programming than the conventional columns.

PMID- 14700228
TI  - An automatic method for the determination of carcinogenic 1-nitropyrene in
      extracts from automobile exhaust particulate matter.
AB  - An automatic method for the determination of carcinogenic 1-nitropyrene in
      extracts from automobile exhaust particulate matter has been developed. Organic
      matter was extracted from particulate matter and the extract was concentrated.
      Then the extract was injected into a two-dimensional (2D) high-performance liquid
      chromatograph (HPLC) with a fluorescence detection system. To improve the
      sensitivity a large sample volume (300 microl) was applied to the HPLC system
      using the double on-column focusing technique. To achieve full automation and
      high selectivity a reduction column packed with platinum black was introduced
      after the 2D HPLC system using a C18 column as the primary column and a
      pentabromobenzyl column as the secondary column. This HPLC system could determine
      0.01-3,000 ng ml(-1) of 1-nitropyrene in an extract from diesel and gasoline
      exhaust particulate matter at 40 min intervals.

PMID- 14700229
TI  - Complexation of silver and co-recovered metals with novel aza-crown ether
      macrocycles by electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is used to evaluate the metal
      binding selectivities of an array of novel caged macrocycles for silver, gold,
      copper, nickel, zinc, iron, lead, manganese and alkali metal ions. It is found
      that five of the new compounds display silver selectivity, and their relative
      affinities for various metals depend on the type, number, and arrangement of
      heteroatoms (N, O), the cavity size, and the presence of aromatic substituents.
      Alkali metal cation binding studies are used to evaluate the size-selectivities
      of the cavities of the macrocycles. Electronic structure calculation by B3LYP
      density function theory methods were used to model the metal complexes. The
      presence of nitrogen atoms in the macrocyclic ring is essential for silver
      selectivity over other transition metals and alkali metal ions, and the presence
      of aromatic groups also enhances silver avidity. Macrocycle 3, a triaza-18-crown
      6 analog modified with two phenyl groups and a cage group, is capable of
      selective extraction of Ag+ from aqueous solutions in the presence of other
      transition metal ions and the most common alkali and alkaline earth metal ions.

PMID- 14700230
TI  - Identification of Shiga toxins in Shiga toxin-producing Escherichia coli using
      immunoprecipitation and high-performance liquid chromatography-electrospray
      ionization mass spectrometry.
AB  - We developed a rapid and reliable identification method for Shiga toxins in Shiga
      toxin-producing Escherichia coli (STEC) using immunoprecipitation and high
      performance liquid chromatography-electrospray ionization mass spectrometry (HPLC
      ESI-MS). Polyclonal antisera specific for Shiga toxin 1 (Stx1) and Shiga toxin 2
      (Stx2) were raised in rabbits so as to be used for the immunoprecipitation. The
      immunoprecipitaion was carried out by mixing sample solutions with 50 microl each
      of the antisera to Stx1 and Stx2 followed by allowing the mixed solutions to
      stand for 30 min. The quantity required to obtain the immunoprecipitate was more
      than 0.5 microg of Shiga toxins. HPLC-ESI-MS analysis of the resulting
      immunoprecipitates provided accurate molecular weight information on Shiga
      toxins, leading to direct evidence for the presence of these toxins. It requires
      at most two days to perform our procedure from toxin extraction to measurement of
      HPLC-ESI-MS whereas the previous method using isolation procedures required about
      two weeks to complete. The usefulness of the present method has been demonstrated
      by identifying Stx1, Stx2 and a variant of Stx2 (Stx2e) in the immunoprecipitates
      prepared from STEC strains.

PMID- 14700231
TI  - LC-electron capture-APCI(-)-MS determination of nitrobenzoxadiazole derivatives.
AB  - Nitrobenzoxadiazole (NBD) derivatives are determined with limits of detection
      ranging down to 20 nmol l(-1) using liquid chromatography-mass spectrometry (LC
      MS) with electron capture (EC) ionisation. An atmospheric pressure chemical
      ionisation (APCI) interface operated in the negative ion mode is used as
      ionisation source. Amine derivatives of 4-chloro-7-nitro-2,1,3-benzoxadiazole
      (NBDCl) as well as the isocyanate derivatives of 4-nitro-7-piperazino-2,1,3
      nitrobenzoxadiazole (NBDPZ) have been analysed using this technique. The
      parameters favouring electron capture mechanisms have been investigated
      thoroughly under consideration of the competing mechanism of deprotonation to
      allow a better understanding of the electron capture process and to improve
      selectivity of the analysis.

PMID- 14700232
TI  - Detection of hormonal anabolic compounds in calf urine and unverified growth
      promoting preparations: application of the AR-LUX bioassay for screening and
      determination of androgenic activity.
AB  - Despite a ban by the European Union, the use of anabolic steroids and
      repartitioning agents in cattle is still occasionally observed. Due to continuing
      improvements in analytical techniques, very low detection limits for individual
      compounds have been achieved. In response to these developments, cocktails
      composed of several steroids have been applied, thus hampering detection due to
      lower levels of the individual compounds. Bioassays capable of measuring the
      integrated effect of cocktails might therefore provide valuable additional tools
      in controlling the use of illegal anabolics. We investigated the feasibility of
      using the AR-LUX assay to detect the presence in cattle urine of growth promoters
      that exert their effects via androgen response elements (AREs). The AR-LUX assay
      is based on a human cell line featuring a luciferase reporter gene under
      transcriptional control of an authenticated ARE. Several column purification and
      liquid/liquid extraction methods were investigated to optimize the efficiency of
      anabolic compounds extraction and minimize cytotoxic effects of the urine matrix.
      The AR-LUX assay was found to be applicable to the detection of anabolic steroids
      excreted in urine samples with a discriminatory power similar to that of GC-MS
      analysis. Finally, some liquid products probably destined for growth-promoting
      purposes confiscated outside the Netherlands were analyzed. Although common
      chemical-analytical methods did not detect any anabolic steroids in these
      samples, the presence of compounds activating ARE-mediated gene expression was
      clearly established.

PMID- 14700233
TI  - Enzyme-dispersed carbon-nanotube electrodes: a needle microsensor for monitoring
      glucose.
AB  - The preparation of an enzyme-dispersed carbon-nanotube (CNT) electrode, based on
      mixing glucose oxidase (GOx) within CNT, is described. The new binderless
      biocomposite was packed within a 21-gauge needle and used for amperometric
      monitoring of glucose. The resulting microsensor offers a low-potential highly
      selective and sensitive detection of glucose. The high sensitivity and
      selectivity are coupled to a wide linear range, prolonged lifetime and oxygen
      independence. About 80% of the GOx activity is retained during a 24 h thermal
      stress at 90 degrees C, reflecting the enzyme-stabilization action of CNT. The
      marked electrocatalytic action towards hydrogen peroxide allows highly selective
      detection of the glucose substrate at -0.1 V (vs. Ag/AgCl) with no interferences
      from coexisting ascorbic acid, acetaminophen or uric acid. Linearity prevails up
      to 40 mM glucose (with analytically useful signals observed up to 0.1 M). Factors
      affecting the performance of the CNT-based glucose biosensor were assessed and
      optimized. The attractive performance of the new needle electrode offers great
      promise for continuous monitoring of glucose in connection to the management of
      diabetes, and for the biosensing of other metabolites.

PMID- 14700234
TI  - Ion selectivity obtained under voltammetric conditions when a TCNQ chemically
      modified electrode is presented with aqueous solutions containing
      tetraalkylammonium cations.
AB  - The voltammetry of 7,7,8,8-tetracyanoquinodimethane (TCNQ) at an electrode
      microparticle-aqueous (electrolye) interface has been proposed as a cation sensor
      on the basis that changes in electrolyte cation (analyte) concentrations result
      in reproducible shifts in the TCNQ0/- reversible potential. In order to probe the
      ion selective nature of the TCNQ sensor, the voltammetric response towards a
      series of tetraalkylammonium cations of variable size and hydrophobicity were
      studied. Both the thermodynamics (reversible potential) and kinetics
      (voltammetric peak separation) of the TCNQ0/- system were strongly dependant on
      the identity of the R4N+ cation. The reversible potential responded in a
      Nernstian manner to changes in cation concentration. When presented with mixed
      analyte solutions, the TCNQ system exhibited Nicolsky type (or competitive) form
      of selectivity. However, the selectivity coefficients found in the present study
      were far greater than previously reported with group I cations. The order
      obtained for the tetraalkylammonium series indicates that ion selectivity is
      predominantly based on analyte solvation thermodyanics rather than a specific
      ionophore mechanism.

PMID- 14700235
TI  - Measurement uncertainty from physical sample preparation: estimation including
      systematic error.
AB  - A methodology is proposed, which employs duplicated primary sampling and
      subsequent duplicated physical preparation coupled with duplicated chemical
      analyses. Sample preparation duplicates should be prepared under conditions that
      represent normal variability in routine laboratory practice. The proposed
      methodology requires duplicated chemical analysis on a minimum of two of the
      sample preparation duplicates. Data produced from the hierarchical design is
      treated with robust analysis of variance (ANOVA) to generate uncertainty
      estimates, as standard uncertainties ('u' expressed as standard deviation), for
      primary sampling (ssamp), physical sample preparation (sprep) and chemical
      analysis (sanal). The ANOVA results allow the contribution of the sample
      preparation process to the overall uncertainty to be assessed. This methodology
      has been applied for the first time to a case study of pesticide residues in
      retail strawberry samples. Duplicated sample preparation was performed under
      ambient conditions on two consecutive days. Multi-residue analysis
      (quantification by GC-MS) was undertaken for a range of incurred pesticide
      residues including those suspected of being susceptible to loss during sample
      preparation procedures. Sampling and analytical uncertainties dominated at low
      analyte concentrations. The sample preparation process contributed up to 20% to
      the total variability and had a relative uncertainty (Uprep%) of up to 66% (for
      bupirimate at 95% confidence). Estimates of systematic errors during physical
      sample preparation were also made using spike recovery experiments. Four options
      for the estimation of measurement uncertainty are discussed, which both include
      and exclude systematic error arising from sample preparation and chemical
      analysis. A holistic approach to the combination and subsequent expression of
      uncertainty is advised.

PMID- 14700236
TI  - Literacy and health in Canada: is it really a problem?

PMID- 14700237
TI  - Literacy in primary care populations: is it a problem?
AB  - BACKGROUND: Almost half of Canadians experience difficulty using print media,
      according to the 1994 International Adult Literacy Survey. Our objectives were to
      estimate the prevalence of low-literacy patients in our practice, to determine
      whether reading grade level is associated with self-perceived health status in
      primary care, and to evaluate the reading difficulty of commonly used patient
      education pamphlets. METHODS: We surveyed a random sample of 229 patients aged 18
      to 85 years presenting for scheduled and walk-in care. Main outcome measures were
      reading ability as estimated by word decoding skill with the validated Rapid
      Estimate of Adult Literacy in Medicine (REALM) and self-perceived health status
      using COOP/WONCA functional health measures. We assessed the reading difficulty
      of 120 commonly used patient education pamphlets using the Simple Measure of
      Gobbledygook (SMOG) formula. RESULTS: The prevalence of low-literate patients was
      9%. Poor reading ability in English was most likely among patients under 45 years
      of age not having completed high school, and among those whose maternal language
      was neither English nor French (immigrants). REALM scores and self-perceived
      health were weakly correlated but not significant statistically. The mean reading
      grade level of pamphlets was grade 11.5 (SD: 1.5). Seventy-eight percent of
      pamphlets required at least a high school reading level. CONCLUSION: Literacy
      levels were higher than expected in our patient population; this finding may be
      due to the rapid assessment tool used, which may have underestimated the
      difficulty of using print media. Clearly, the vast majority of commonly used
      patient education materials would not meet the needs of low-literate patients,
      who may be more likely to experience poorer health. Providers need to be
      sensitive to the reading limitations of patients and patient education materials
      should be written at a lower reading level.

PMID- 14700238
TI  - Canadian health care and child rights--what are the links?

PMID- 14700239
TI  - The status of drinking water in Ontario, Canada (1992-1999).
AB  - OBJECTIVE: This study was conducted to investigate the characteristics of public
      water works (PWW) in southern Ontario with respect to their water sources and
      treatment regimes. METHODS: Data from 481 PWW covering the period 1992-1999 were
      collected and cartographic manipulations as well as descriptive analyses of the
      PWW attributes were performed. Tests of associations between different PWW
      attributes were done using Fisher's Exact test and Cochran-Mantel-Haenszel
      statistics. RESULTS: Water sources for the PWW included surface water (SW) (21%
      lakes; 13% rivers), ground water (GW) (64%) and mixed sources (2%). Most (81%) of
      the population was supplied with SW. Filtration was performed by 84% and 8% of
      the PWW using SW and GW, respectively. Similarly, disinfection was performed by
      99% and 91% of the PWW using SW and GW respectively. There was no significant
      difference in treatment regimes between PWW in urban and those in rural areas but
      treatment regime was a function of water source. Overall, most PWW (87.8%) met
      the minimum treatment requirements of the then Ontario Drinking Water Objectives
      (ODWO). DISCUSSION: The study shows that most PWW complied with the minimum
      treatment requirements of the then ODWO. The minimum treatment required by the
      ODWO was disinfection for GW and both disinfection and filtration for SW. The non
      compliant PWW will need to comply for continued provision of safe drinking water.
      Suffice it to say that both watershed protection and improved water treatment
      will be imperative for the continued provision of safe drinking water and control
      of waterborne diseases.

PMID- 14700240
TI  - Women's perceptions of breast cancer risk: are they accurate?
AB  - BACKGROUND: The objective was to compare women's personal estimates of their risk
      with objective breast cancer risk estimates and to describe the risk factors for
      breast cancer identified by women. METHODS: Telephone survey of a random sample
      of 761 rural and urban women with no history of breast cancer. Survey instrument
      included measures of perceptions of lifetime risk for breast cancer for
      themselves and for the average woman, perceptions of risk factors that influenced
      their risk and the average woman's risk for breast cancer. Objective estimates of
      breast cancer risk were calculated using the Gail et al. algorithm. Descriptive
      statistics and multiple linear regression were used to analyze the data. RESULTS:
      Women's estimates of their own lifetime risk for breast cancer were significantly
      higher than their Gail model risk estimates (mean difference = 19%, p < 0.001).
      The women's personal breast cancer risk estimates were lower than estimates of
      risk for a hypothetical average woman (mean difference = -8%, p < 0.001). Fifty
      percent of the sample reported a perceived risk estimate at least 15% above their
      Gail risk estimate. The risk factors for breast cancer most frequently identified
      included family history, nutrition/diet, smoking, lifestyle, environment, stress
      and age. Although the risk factors used to calculate the Gail model risk
      estimates were reported by some study participants, these women consistently
      identified only family history as their personal risk factor. CONCLUSION: Women
      have difficulty accurately estimating their breast cancer risk and identifying
      known risk factors for breast cancer. Individual risk information may be more
      useful in enhancing accurate risk perceptions than the "1 in 9" message.

PMID- 14700241
TI  - Breaking--bad news: women's experiences of fractures at midlife.
AB  - OBJECTIVE: To gain understanding of the experiences and sequelae of fractures in
      women aged 40-65 years and to assess whether it is linked to overall bone health
      assessment. METHOD: A qualitative study using face-to-face indepth interviews.
      FINDINGS: Contrary to the common belief that fractures are benign, for middle
      aged women, fractures have a significant impact on their well-being in both the
      short and long-term. Women report significant pain as well as an immediate need
      for help from family and professional caregivers. They experience interruptions
      to daily and leisure activities, employment, daily life and mobility. Only a
      minority of women and/or their family physicians initiated follow up to
      investigate bone health subsequent to the fracture. CONCLUSIONS: Bone health is
      often examined in the context of already established bone disease. This study
      suggests a need for a closer examination of fracture treatment in the context of
      preventive care, and early detection of osteoporosis.

PMID- 14700242
TI  - Regional variation in HIV prevalence and risk behaviours in Ontario injection
      drug users (IDU).
AB  - OBJECTIVES: To measure HIV prevalence, risk behaviours, and further service needs
      in needle exchange programs throughout Ontario, and to conduct regional
      comparisons. METHODS: Injection drug users (IDU) recruited through the efforts of
      needle exchange programme (NEP) staff in 9 Ontario cities during 1997-98
      completed questionnaires about their drug use and behaviours and provided saliva
      and/or dried blood samples for anonymous unlinked HIV testing. RESULTS:
      Demographic and drug use characteristics of participants showed great regional
      variation. HIV prevalence by region ranged from 1.4% to 14.7%. In addition to
      region, HIV positivity was associated with injecting for more than 5 years, use
      of (powder) cocaine, use of crack, binge injection (10 or more times per day at
      least once in the previous 6 months), and being a longer-term NEP user. Sharing
      of injection equipment, and especially of other drug injection materials such as
      water and cookers, remain important issues, although much of the sharing reported
      is with only one other person. Unmet demand for methadone treatment was
      identified despite changes in regulation of methadone provision designed to make
      it more accessible. CONCLUSIONS: This study suggested significant further HIV
      prevention needs among IDU throughout Ontario. There is also evidence of
      potential to provide additional services such as methadone at NEPs if the
      required resources are invested. NEPs that have succeeded in gaining the trust of
      high-risk IDU offer a means to provide access to needed services.

PMID- 14700243
TI  - The relationship between housing conditions and health status of rooming house
      residents in Toronto.
AB  - BACKGROUND: Rooming houses are an important source of housing for low-income
      Canadians. Little information is available on the relationship between housing
      conditions and health status in this vulnerable population. METHODS: Interviews
      were conducted with a representative sample of 295 residents in 171 rooming
      houses in Toronto. Health status was assessed using the SF-36. The physical
      attractiveness of each rooming house was rated using the Multiphasic
      Environmental Assessment Procedure. Associations between the health status of
      residents and the physical attractiveness and organizational characteristics of
      rooming houses were examined. RESULTS: Rooming house residents aged 35 years and
      older had significantly poorer health status than their counterparts in the
      Canadian general population. Eight of the ten dimensions of individual health
      status assessed by the SF-36 were significantly correlated with the physical
      attractiveness of the rooming house in which the individual lived. However, there
      was no significant association between residents' health status and the rooming
      house's non-profit status, provision of meals, or the presence of an on-site
      landlord. CONCLUSIONS: Rooming house residents suffer from a high prevalence of
      ill health. Residents reporting worst health are concentrated in rooming houses
      in the poorest physical condition. This relationship may be mediated by selection
      processes that place the sickest individuals in the lowest-quality rooming
      houses, and/or by a direct effect of adverse housing conditions on health status.
      Further research is needed to elucidate these processes and to improve the health
      of this vulnerable population.

PMID- 14700244
TI  - Association of socio-economic factors with health risk behaviours among high
      school students in rural Nova Scotia.
AB  - OBJECTIVE: To determine the association of socio-economic (SES) factors with risk
      behaviours among adolescents. METHODS: A cross-sectional survey was carried out
      on students in four high schools in northern Nova Scotia, Canada. Associations
      between SES variables and substance use behaviours, having early intercourse and
      suicide attempt in the past year were examined using multivariate analysis (logit
      regression). Negative binomial regression was performed for associations of SES
      with a total risk score summing risk behaviours. RESULTS: Participants included
      2,198 students (48% males; 52% females) ranging in age from 14 to 20 years.
      Almost 25% of youth smoked regularly, 19% of males smoked marijuana > or = 10
      times monthly, more than 40% of males regularly drank excessively, and 10% of
      students > 14 years old had had intercourse before age 15. Smoking was the
      behaviour most often associated with lower SES in both genders. Mother's not
      being employed was protective against all substance use variables except driving
      after drinking. Living both with lone mother and in any family arrangement other
      than with both parents was associated with smoking, using marijuana, and early
      sex. Higher risk score was associated with living with a lone mother or other
      family arrangement. Lower risk score was associated with father having more than
      high school education and mother not working. INTERPRETATION: Lower socio
      economic status is associated with adolescent risk behaviours. These findings
      point to the importance of these factors to risk-taking in youth, their relevance
      to social policy, and also their importance as factors to consider in targeted
      interventions.

PMID- 14700245
TI  - Teachers' perspective on barriers to implementing physical activity curriculum
      guidelines for school children in Toronto.
AB  - BACKGROUND: Teachers in Ontario are expected to implement the physical activity
      guidelines in the health and physical education (HPE) curriculum document that
      was introduced in 1998. This study examined Toronto teachers' perspective on
      barriers to implementing these guidelines. METHODS: Forty-five teachers from five
      Toronto elementary schools in which generalist classroom teachers provide
      physical education classes participated in focus groups. An experienced moderator
      facilitated each session. Themes were inductively generated from the data.
      RESULTS: Participants reported that children were not engaged in moderate or
      vigorous physical activity daily and for the expected duration. Participants
      identified three categories of barriers to implementing the curriculum
      guidelines: lower priority for HPE, lack of performance measures for physical
      activity, and lack of sufficient infrastructure. First, they reported that the
      new curriculum expectations for other subjects were demanding, which left little
      time to focus on physical education. They felt that resource support for the HPE
      curriculum was not sufficient and that physical education specialists were
      necessary but unavailable to implement the curriculum. Second, participants felt
      accountable to both government and parents for high student performance on
      standardized tests in subjects deemed to be of higher priority. Third,
      participants reported inadequate facilities and equipment, use of portables for
      classrooms, cancelling physical education to have events in the gymnasium, and
      unavailability of teachers to supervise off-school physical activity. CONCLUSION:
      The study suggests that participating teachers perceive physical education to be
      a low priority in the educational system, making it difficult for them to meet
      the HPE curriculum expectations.

PMID- 14700246
TI  - The seasonality of total hospitalizations in Ontario by age and gender: a time
      series analysis.
AB  - BACKGROUND: Consistent and predictable seasonal fluctuations in hospitalizations
      have been demonstrated for diverse communicable and non-communicable health
      conditions. The objective of this study was to examine the seasonal patterns of
      all hospitalizations by age and gender in order to determine whether the hospital
      system for a large geographical area was subject to consistent, predictable
      temporal variations. METHODS: A retrospective population-based study of
      approximately 14 million residents of Ontario was conducted to assess temporal
      patterns in all hospitalizations from April 1, 1988 to March 31, 2000. Time
      series analysis, using spectral analysis, was conducted to assess seasonal
      variations and trends over time and to account for autocorrelation. RESULTS:
      Conspicuous seasonality in hospitalizations was found in every age group for both
      sexes with the exception of males between the ages of 20 and 39. The average
      monthly variability ranged from lows of 15% for the age group 20-29 for both
      sexes, to highs of 34% in males between 5 and 9 years. For the total population,
      this represents a 12-year average variability of approximately 20% or 20,000 out
      of 97,000 hospitalizations. For both sexes, peak hospitalizations typically
      occurred in the spring and autumn for the youngest and oldest age groups, and in
      January for the middle age groups. CONCLUSION: Seasonal factors play an important
      role in the utilization of hospital services in Ontario. The determinants of this
      seasonality, which include environmental and social/behavioural factors, are not
      well understood.

PMID- 14700247
TI  - Trends in emergency department reported head and neck injuries among skiers and
      snowboarders.
AB  - BACKGROUND: Reports from the U.S. suggest increases in the proportion and rate of
      head and neck injuries in skiers and snowboarders. It is important to determine
      if the same is true in Canada. METHODS: Skiers and snowboarders (< 18 years)
      presenting to 16 selected emergency departments from 1991 to 1999 were assigned
      one body region of injury in the following order: i) brain and spine-spinal cord,
      ii) head and neck, iii) face, iv) other body region (i.e., controls). Crude and
      adjusted (age, gender, helmet use and hospital admission) odds ratios indicating
      the proportion of head, brain, face, and neck injury relative to controls by
      calendar year were estimated. Injury rates were examined for 12 to 17 year olds
      over the last 4 years of the study. RESULTS: Compared with 1997-1999, there was a
      lower proportion of skier head injuries from 1991-93 (adjusted odds ratio (AOR) =
      0.16; 95% Confidence Interval (CI) = 0.09-0.30) and from 1995-97 (AOR = 0.71; 95%
      CI = 0.49-1.04). The proportion of skier brain injuries was lower from 1993-95
      (AOR = 0.69; 95% CI = 0.44-1.07) and from 1995-97 (AOR = 0.56; 95% CI: 0.35
      0.91). In snowboarders, however, compared with 1997-99, there was evidence that
      although the proportion of head injuries was lower from 1991-93 (AOR = 0.19; 95%
      CI = 0.05-0.80), the opposite was true for facial injuries. For 12 to 17 year
      olds, skier brain and snowboarder head and neck injury rates increased from 1995
      99. CONCLUSIONS: The results suggest that head and brain injuries in skiers and
      head and neck injuries in snowboarders may be increasing, particularly in
      adolescents.

PMID- 14700248
TI  - Under-reporting of live births in Ontario: 1991-1997.
AB  - OBJECTIVE: To examine unregistered births in Ontario and consider related
      factors, including adoption of administrative fees for birth registration.
      METHODS: Documents from both the parents and the attending physician are required
      for births to be entered into Ontario's live birth database. Our study used data
      from the Ontario Registrar General to look at the prevalence and characteristics
      of unregistered births, and a survey of municipal clerks to identify
      municipalities charging fees for parental documentation. RESULTS: The percentage
      of births going unrecorded increased threefold from 1991 to 1997. The odds of an
      unregistered birth were higher for teenage mothers, low birthweight babies, and
      mothers residing in a municipality that charged birth registration fees.
      CONCLUSION: The introduction of registration fees by some municipalities appears
      to account for an increase in unregistered births. It is recommended that the
      Ontario Registrar General work to remove financial and administrative barriers
      that compromise birth statistics.

PMID- 14700250
TI  - Functional seeing.

PMID- 14700249
TI  - Integrating knowledge generation with knowledge diffusion and utilization: a case
      study analysis of the Consortium for Applied Research and Evaluation in Mental
      Health.
AB  - OBJECTIVE: Knowledge diffusion and utilization (KDU) have become a key focus in
      the health research community because of the limited success to date of research
      findings to inform health policies, programs and services. Yet, evidence
      indicates that successful KDU is often predicated on the early involvement of
      potential knowledge users in the conceptualization and conduct of the research
      and on the development of a "partnership culture". This study describes the
      integration of KDU theory with practice via a case study analysis of the
      Consortium for Applied Research and Evaluation in Mental Health (CAREMH).
      METHODS: This qualitative study, using a single-case design, included a number of
      data sources: proposals, meeting minutes, presentations, publications, reports
      and curricula vitae of CAREMH members. RESULTS: CAREMH has adopted the following
      operational strategies to increase KDU capacity: 1) viewing research as a means
      and not as an end; 2) bringing the university and researcher to the community; 3)
      using participatory research methods; 4) embracing transdisciplinary research and
      interactions; and 5) using connectors. Examples of the iterative process between
      researchers and potential knowledge users in their contribution to knowledge
      generation, diffusion and utilization are provided. CONCLUSIONS: This case study
      supports the importance of early and ongoing involvement of relevant potential
      knowledge users in research to enhance its utilization potential. It also
      highlights the need for re-thinking research funding approaches.

PMID- 14700251
TI  - Meet The Simpsons: top-down effects in face learning.
AB  - We examined whether prior knowledge of a person affects the visual processes
      involved in learning a face. In two experiments, subjects were taught to
      associate human faces with characters they knew (from the TV show The Simpsons)
      or characters they did not (novel names). In each experiment, knowledge of the
      character predicted performance in a recognition memory test, relying only on
      old/new confidence ratings. In experiment 1, we established the technique and
      showed that there is a face-learning advantage for known people, even when face
      items are counterbalanced for familiarity across the experiment. In experiment 2
      we replicated the effect in a setting which discouraged subjects from attending
      more to known than unknown people, and eliminated any visual association between
      face stimuli and a character from The Simpsons. We conclude that prior knowledge
      about a person can enhance learning of a new face.

PMID- 14700252
TI  - The effects of different aperture-viewing conditions on the recognition of novel
      objects.
AB  - The process of learning the structure of novel objects involves the selective use
      of information available in the distal stimulus. By allowing participants to
      explore the object within a limited field of view, we were able to examine more
      rigorously what regions of the object are actually selected in the learning
      process. Participants explored objects either by moving a circular aperture over
      a stationary novel object (the aperture-movement condition), or by moving the
      object behind a stationary aperture (the object-movement condition). Given the
      differences in how the spatial layout of object parts is revealed in the two
      study conditions, we expected that exploration would be more systematic in the
      aperture-movement condition than it would be in the object-movement condition,
      and would lead to better object recognition. We show evidence that in the
      aperture-movement condition exploration patterns were more related to the
      structure of the object and, as a consequence, the aperture-movement condition
      resulted in more accurate recognition in a later old--new discrimination test.

PMID- 14700253
TI  - Configural processing in the perception of eye-gaze direction.
AB  - Traditional accounts of gaze perception emphasise the geometric or configural
      cues present in the eye; the position of the iris in relation to the corner of
      the eye, for example. This kind of geometric account has been supported, in part,
      by findings that gaze judgments are impaired in faces rotated through 180
      degrees, a manipulation known to disrupt the processing of relations between
      facial elements. However, studies involving this manipulation have confounded
      inversion of the face context with inversion of the eye region. The effects of
      inversion might therefore have been caused by a disruption of the computation of
      gaze direction from the eye region itself and/or a disruption of the influence
      that face context might exert on gaze processing. In the experiment reported here
      we independently manipulated eye orientation and the orientation of the face
      context, and measured participants' sensitivity to gaze direction. Performance
      was severely affected by inversion of the eyes, regardless of the orientation of
      the face, whereas face inversion had no significant effect on gaze sensitivity.
      Previous reports of a face-inversion effect on gaze perception can therefore be
      attributed to inversion of the eye region itself which, we suggest, disrupts some
      form of configural or relational processing that is normally involved in the
      computation of eye-gaze direction.

PMID- 14700254
TI  - Effects of partial occlusion on perceived surface segregation.
AB  - Tests are reported of the possibility that local information from contour
      junctions and from corners of intersecting surfaces is used for perceived surface
      segregation. Stimuli were two intersecting squares with small disks occluding
      different parts of the squares. The perceived segregation of the squares from one
      another decreased as the amount of occlusion of parts of the squares increased.
      This segregation was less when disks occluded parts of contours than when disks
      occluded parts entirely inside the squares. Occlusion of parts of contours
      reduced segregation independently of whether contour junctions or corners were
      visible or invisible, both where the intersecting surfaces were transparent
      squares and when they were outlined squares. The present findings show that local
      information from contour junctions or from corners is not used for surface
      segregation, and confirm that this segregation is determined by global processes
      of grouping of areas and of extrapolation of contours.

PMID- 14700255
TI  - Orientation-selective adaptation to crowded illusory lines.
AB  - Visual adaptation has been successfully used as a psychophysical tool for
      studying the functional organisation of visual awareness. It has been shown that
      orientation-selective adaptation to a grating pattern occurs in crowded
      conditions. In such conditions, simultaneous presentation of flanking distractors
      pushes the target stimulus out of conscious perception and severely impairs
      orientation discrimination in the periphery of the visual field. In the present
      study, orientation-selective adaptation to illusory lines induced by two line
      gratings abutting each other with a phase shift was examined in crowded and non
      crowded conditions. To rule out the effects of lower level adaptations we used an
      animation paradigm in which the orientations of the two line gratings were
      altered repeatedly during adaptation phase without any change in the orientation
      of the resulting illusory line. Although performance of subjects in reporting the
      orientation of crowded illusory lines was at chance level, orientation-selective
      adaptation was preserved for crowded as well as non-crowded adapting targets. Two
      control experiments demonstrated that adaptation to endpoints of real lines at
      the location of abutting grating lines had minimal effect on the adaptation to
      illusory lines; and changes in the configuration of endpoints could not be
      responsible for better performance when adapting and test stimuli were different.
      We conclude that a crowding effect occurs after illusory lines have been
      processed in the visual stream. Since illusory lines seem to be represented at
      relatively early stages of visual processing (e.g. area V2), adaptation to
      crowded illusory stimuli suggests that neuronal activation in those early stages
      is not necessarily correlated with conscious perception.

PMID- 14700256
TI  - Spatial integration in Glass patterns.
AB  - The extraction of a global orientation structure presumably has a different
      neural mechanism from that of the analysis of its local features. We investigated
      spatial integration within these two mechanisms using stimulus patterns composed
      of dot pairs (dipoles). The stimuli targeted local feature detection, contained
      no global configuration, but rather contained randomly oriented dipoles of a
      fixed length (the distance between the dots in a pair). For the detection of a
      global orientation structure, local dipole orientations were arranged in a
      concentric Glass pattern. Thresholds as a function of a stimulus area were
      determined by measuring the minimum proportion of dipoles among random-dot noise
      (signal-to-noise ratio) required for the detection of dipoles (features), as well
      as for the detection of an orientation structure. Thresholds for feature
      detection were significantly higher than those for the detection of the global
      structure--regardless of the stimulus size. Spatial integration, however, did not
      differ between the two tasks: the exponents of the power functions fitted to data
      for six observers were -0.48 +/- 0.07 for random dipole orientations and -0.62 +/
      0.1 for Glass patterns.

PMID- 14700257
TI  - Motion, flash, and flicker: a unified spatiotemporal model of perceived edge
      sharpening.
AB  - Blurred edges appear sharper in motion than when they are stationary. We proposed
      a model of this motion sharpening that invokes a local, nonlinear contrast
      transducer function (Hammett et al, 1998 Vision Research 38 2099-2108). Response
      saturation in the transducer compresses or 'clips' the input spatial waveform,
      rendering the edges as sharper. To explain the increasing distortion of drifting
      edges at higher speeds, the degree of nonlinearity must increase with speed or
      temporal frequency. A dynamic contrast gain control before the transducer can
      account for both the speed dependence and approximate contrast invariance of
      motion sharpening (Hammett et al, 2003 Vision Research, in press). We show here
      that this model also predicts perceived sharpening of briefly flashed and
      flickering edges, and we show that the model can account fairly well for
      experimental data from all three modes of presentation (motion, flash, and
      flicker). At moderate durations and lower temporal frequencies the gain control
      attenuates the input signal, thus protecting it from later compression by the
      transducer. The gain control is somewhat sluggish, and so it suffers both a slow
      onset, and loss of power at high temporal frequencies. Consequently, brief
      presentations and high temporal frequencies of drift and flicker are less
      protected from distortion, and show greater perceptual sharpening.

PMID- 14700258
TI  - Spatial variations of visual-auditory fusion areas.
AB  - The tolerance to spatial disparity between two synchronous visual and auditory
      components of a bimodal stimulus has been investigated in order to assess their
      respective contributions to perceptual fusion. The visual and auditory systems
      each have specific information-processing mechanisms, and provide different cues
      for scene perception, with the respective dominance of space for vision and of
      time for hearing. A broadband noise burst and a spot of light, 500 ms in
      duration, have been simultaneously presented to participants who had to judge
      whether these cues referred to a single spatial event. We examined the influence
      of (i) the range and the direction of spatial disparity between the visual and
      auditory components of a stimulation and (ii) the eccentricity of the bimodal
      stimulus in the observer's perceptual field. Size and shape properties of visual
      auditory fusion areas have been determined in two dimensions. The greater the
      eccentricity within the perceptual field, the greater the dimension of these
      areas; however, this increase in size also depends on whether the direction of
      the disparity is vertical or horizontal. Furthermore, the relative location of
      visual and auditory signals significantly modifies the perception of unity in the
      vertical plane. The shape of the fusion areas, their variation in the field, and
      the perceptual result associated with the relative location of the visual and
      auditory components of the stimulus, concur towards a strong contribution of
      audition to visual-auditory fusion. The spatial ambiguity of the localisation
      capabilities of the auditory system may play a more essential role than accurate
      visual resolution in determining fusion.

PMID- 14700259
TI  - Visual processing of coherent rotation in the central visual field: an fMRI
      study.
AB  - Functional magnetic resonance imaging was used to determine the brain areas that
      process coherent motion. To reduce the activity related to eye-movement planning
      and self-motion perception, rotation was used as coherent motion and the stimulus
      was restricted to the central visual field. Coherent rotation relative to
      incoherent random-dot motion resulted in consistent activation in the superior
      parietal lobule (SPL), in the lateral occipital gyrus (presumptive kinetic
      occipital region, KO), and in the fusiform gyrus (FG). The main novel finding in
      present study is the bilateral SPL activation, which has not been found in any
      previous study contrasting coherent and incoherent motion. It is suggested that
      the SPL activation is related to form-from-motion processing. The stimulus
      modification that prevented abrupt appearances of dots at the borders of the
      stimulus field increased the strength of rolling disk-like percept of the
      coherent stimulus. This perception of form may also be at least partly
      responsible for the activation in KO and FG. With this explanation, our three
      consistent activation areas are in line with previous findings. Furthermore,
      these results demonstrate that even delicate changes in some stimulus aspects can
      lead to significant changes in the activation of the brain.

PMID- 14700260
TI  - Detection of amplitude modulation and frequency modulation in tactual gratings: a
      critical bandwidth for active touch.
AB  - Since most natural surfaces are complex and vary in amplitude and spatial
      frequency, it might be interesting to consider gratings not in the spatial
      domain, but in the spatial-frequency domain. Detection thresholds for amplitude
      modulation (AM) and frequency modulation (FM) in sinusoidal gratings were
      measured for seven participants. Participants moved their fingers actively across
      the gratings. Although the two types of modulation are quite different in the
      spatial domain, they have many features in common in the frequency domain. In
      previous research (Nefs et al 2001 Perception 30 1263-1274) we measured the
      discrimination thresholds for amplitude and frequency for sinusoidal gratings. We
      hypothesised then that these thresholds could be used to predict the
      discriminability of other types of gratings. In the present study, we did indeed
      find that the FM and AM detection thresholds can be understood quite well by
      these discrimination thresholds. The results indicate that the tactual system
      contains parallel psychophysical channels that filter and integrate the power of
      stimuli within critical bands. With these results, we are also able to calculate
      the critical bandwidth for active dynamic touch. We estimated the critical
      bandwidth surrounding the spatial frequency of 2 cycles cm(-1) to be about 125%
      of that spatial frequency. This value for the critical band for spatial frequency
      is incompatible with previous findings for temporal frequencies in vibrotactile
      research. This indicates that dynamic spatial-frequency discrimination is not
      likely to be done by temporal frequency.

PMID- 14700261
TI  - Motion induction from biological motion.
AB  - A new type of motion illusion is described in which ambiguous motion becomes
      unidirectional on superimposition of a human figure walking on a treadmill. A
      point-light walker in profile was superimposed on a vertical counterphase grating
      backdrop. Eleven naive observers judged the apparent direction of motion against
      the grating as left or right in a two-alternative forced-choice task and found
      that the grating appeared to drift in a direction opposite to the walking. The
      illusion disappeared when the point lights moved in scrambled configurations.
      This indicates that the illusion is caused by biological motion that provides
      recognition of gaits. A human figure walking backwards produced no illusion
      because of the difficulty in identifying the gait. This indicates that the
      illusion is determined by translational motion rather than form represented from
      biological motion.

PMID- 14700262
TI  - Experimental and numerical determination of initial tooth mobility and material
      properties of the periodontal ligament in rat molar specimens.
AB  - The mechanical parameters of the periodontal ligament (PDL) in rat specimens were
      investigated in a combined experimental and numerical approach. Tooth mobility of
      the rat mandibular first molar was measured in vitro using a high precision
      experimental set-up. Finite element models (FEM) were developed, based on
      histological sections of the measured specimens, to simulate tooth mobility
      numerically under the same force systems as used in the experiment.
      Force/deflection curves from the measurements showed a significant non-linear
      behaviour of elastic stiffness of the PDL. A bilinear material parameter set was
      assumed to simulate tooth deflections. The numerical force/deflection curves were
      fitted to the experimental curves by repeatedly calculating theoretical tooth
      deflections and varying the parameters describing the non-linearity. Mean values
      of E1 = 0.15 MPa, E2 = 0.60 MPa and an ultimate strain of epsilon12 = 6.3 per
      cent were derived for the elastic behaviour of the rat PDL. Comparing fresh
      specimens and those frozen in a 0.9 per cent saline solution, differences between
      the measurements were significant. Using the agent, Periston, for freezing
      significantly reduced the deviation. The results indicated that strains in the
      PDL with a maximum of 14 per cent at the furcation were 10(4) times higher than
      strains in the bone, while the variability of stress values in both PDL and bone
      was not significant.

PMID- 14700263
TI  - Periodontal status following surgical-orthodontic alignment of impacted central
      incisors with an open-eruption technique.
AB  - Several factors may affect the outcome of the orthodontic/surgical modality for
      the resolution of impacted central incisors, but particularly the manner in which
      the impacted tooth is exposed. The present study aimed to evaluate the post
      retention clinical appearance and periodontal status of impacted maxillary
      central incisors which were exposed and aligned with an open-eruption surgical
      orthodontic technique. Twelve subjects (four males, eight females), aged 22 years
      (range 15-38 years), previously treated for a unilateral impacted central incisor
      (ICI), were examined 10 years (range 3-25 years) post-retention. A split-mouth
      method was used for the comparison with the unaffected side. One treated central
      incisor exfoliated 10 years post-retention, thus the results were based on the
      remaining 11 patients. Statistically significant differences were found between
      the affected and control incisors in most of the periodontal parameters measured,
      although some were small and of minimal clinical importance. The increase in the
      mesio-labial pocket depth was associated with a highly significant 10 per cent
      reduction in bone level at this site (P = 0.007). A highly statistically
      significant increase in crown length (P < 0.001) and a reduction in the width of
      the attached gingiva (P = 0.005) were seen in these previously impacted teeth. An
      abnormal gingival contour was present in eight treated incisors and positional
      relapse in five cases. It is concluded that the convenience of the open-eruption
      technique must be weighed against the long-term negative aesthetic and
      periodontal effects on the treated tooth, although the findings of this study
      should be viewed with caution due to the limited sample size.

PMID- 14700264
TI  - Localizing ectopic maxillary canines--horizontal or vertical parallax?
AB  - This study compared the use of horizontal parallax (HP) and vertical parallax
      (VP) radiography for localizing ectopic maxillary canines (EMCs). The true
      positions of 43 EMCs were determined using the operative notes and subsequent
      study models following exposure and eruption. Thirty-four palatal and nine buccal
      EMCs were included in the study. Six experienced orthodontists examined the
      radiographs of the EMCs and were asked to localize each EMC using VP and HP on
      separate occasions. The examiners recorded a diagnosis of 'unsure' in 12 per cent
      of cases using VP and in 5 per cent of cases using HP. The level of agreement of
      the diagnoses with the true position of the EMCs was significantly greater for
      HP. Eighty-three per cent of EMCs were correctly located with HP while only 68
      per cent were correctly located with VP (P < 0.05). The diagnostic sensitivity
      for palatally placed canines was significantly greater for HP (88 per cent) than
      for VP (69 per cent). Both techniques performed poorly when used to localize
      buccal EMCs, with HP and VP each having a sensitivity of only 63 per cent. It is
      concluded that HP is superior to VP in diagnostic accuracy, and that two peri
      apical radiographs or one peri-apical and one anterior occlusal radiograph are
      the radiographs of choice for localizing EMCs.

PMID- 14700265
TI  - Changes in occupational health problems and adverse patient reactions in
      orthodontics from 1987 to 2000.
AB  - The purpose of the present investigation was to assess the reasons for changes in
      occupational health problems and patient reactions to orthodontic treatment after
      a survey carried out in 1987. Questionnaire data on occupation-related health
      complaints and patient reactions over the preceding 2 years were obtained from
      121 of 170 Norwegian orthodontists (71 per cent). Most health complaints were
      dermatoses of the hands and fingers related to the processing of acrylic
      removable appliances, to composite bonding materials, or gloves. A few reactions
      were of a respiratory or systemic nature. In total, occupation-related dermatoses
      were reported by 17.4 per cent (21/121) compared with 40 per cent previously. Non
      dermal complaints comprised 9 per cent compared with 18.2 per cent in 1987.
      Patient reactions were distributed equally between intra-oral reactions affecting
      lips, gingiva, oral mucosa, and tongue, and dermal reactions affecting the corner
      of the mouth, the dorsal part of the neck, the peri-oral area, cheeks, chin or
      skin elsewhere. A few patients had systemic reactions. The assumed eliciting
      agents of intra-oral reactions were fixed metallic appliances, acrylic removable
      appliances, polymer brackets or composite bonding materials, or were related to
      elastics. Extra-oral (dermal) reactions were attributed to metallic, elastic or
      textile parts of the extra-oral appliances. Some reactions were verified as
      allergies. The percentage of patient reactions in total was estimated to be 0.3
      0.4 per cent compared with 0.8-0.9 per cent in 1987. The reduction in occupation
      related health complaints among orthodontists was explained by changes in
      previously important hygiene factors such as soaps, detergents, etc., whereas the
      biomaterials-related reactions persisted. The reduction in the 2 year incidence
      of patient reactions was associated with a marked reduction in extra-oral
      reactions following preventive measures such as coating metallic devices, whereas
      the intra-oral reactions persisted at the same level as previously.

PMID- 14700266
TI  - Growth prediction in Class III patients using cluster and discriminant function
      analysis.
AB  - This longitudinal retrospective cephalometric study was undertaken in an attempt
      to identify subgroups of subjects with Class III malocclusions and to find
      discriminant functions which would help to differentiate between favourable and
      unfavourable growers. The material consisted of cephalometric films of 115 Class
      III untreated patients (59 females and 56 males, with a mean age of 11.6 +/- 1.7
      and 12.7 +/- 1.3 years, respectively) who were observed for a minimum period of 1
      year. All subjects were Caucasian and none could achieve an edge to edge
      occlusion. Hierarchical cluster analysis was used to identify Class III
      subgroups. Discriminant function analysis (DFA) was first applied to the whole
      sample and later to each of the clusters produced. Good and poor growers were
      identified on the basis of the change in Wits measurements with projection on the
      maxillary/mandibular planes bisector. The cut-off point between good and bad
      growers was a Wits value of 2.5 mm which was the upper limit of the 95 per cent
      confidence interval of measurement reproducibility. Three clinically
      distinguishable clusters were produced, namely long, short and intermediate
      facial types. The discrimination percentage (80 per cent) achieved when the DFA
      was performed on the whole sample was satisfactory. However, when the analysis
      was used on each of the clusters separately, the equation successfully predicted
      a good or poor outcome in 92 per cent of cluster I, in 85 per cent of cluster II
      and in 100 per cent of cluster III.

PMID- 14700267
TI  - Resin-modified glass ionomer, modified composite or conventional glass ionomer
      for band cementation?--an in vitro evaluation.
AB  - The aims of this study were to compare the mean shear-peel bond strength and
      predominant site of bond failure of micro-etched orthodontic bands cemented with
      resin-modified glass ionomer cement (RMGIC; Fuji Ortho LC or 3M Multi-Cure), a
      modified composite or a conventional GIC. The survival time of bands was also
      assessed following simulated mechanical stress in a ball mill. One hundred and
      twenty molar bands were cemented to extracted human third molars. Eighty bands
      (20 cemented with each cement) were used to assess the debonding force and 40
      bands (10 cemented with each cement) were used to determine survival time. The
      specimens were prepared in accordance with the manufacturers' instructions for
      each cement. After storage in a humidor at 37 degrees C for 24 hours, the shear
      debonding force was assessed for each specimen using a Nene M3000 testing machine
      with a crosshead speed of 1 mm/minute. The predominant site of band failure was
      recorded visually for all specimens as either at the band/cement or cement/enamel
      interface. Survival time was assessed following application of mechanical stress
      in a ball mill. There was no significant difference in mean shear-peel bond
      strength between the cement groups (P = 0.816). The proportion of specimens
      failing at each interface differed significantly between cement groups (P <
      0.001). The predominant site of bond failure for bands cemented with the RMGIC
      (Fuji Ortho LC) or the modified composite was at the enamel/cement interface,
      whereas bands cemented with 3M Multi-Cure failed predominantly at the cement/band
      interface. Conventional GIC specimens failed mostly at the enamel/cement
      interface. The mean survival time of bands cemented with either of the RMGICs or
      with the modified composite was significantly longer than for those cemented with
      the conventional GIC. The findings indicate that although there appears to be
      equivalence in the mean shear-peel bond strength of the band cements assessed,
      the fatigue properties of the conventional GIC when subjected to simulated
      mechanical stress seem inferior to those of the other cements for band
      cementation.

PMID- 14700268
TI  - An in vitro study into the corrosion of intra-oral magnets in the presence of
      dental amalgam.
AB  - The aim of this investigation was to study the corrosion behaviour and products
      of uncoated neodymium-iron-boron magnets in the presence of dental amalgam.
      Microcosm plaques were grown on discs of neodymium-iron-boron magnets or amalgam
      in a constant depth film fermentor. The biofilms were supplied with artificial
      saliva and growth was determined by viable counting. The results showed that the
      neodymium-iron-boron magnets corroded with an average daily weight loss of 0.115
      +/- 0.032 per cent. However, when the magnets were in close proximity to the
      amalgam the amount of corrosion was reduced to a daily loss of 0.066 +/- 0.023
      per cent. The highest loss of constituent elements from the corrosion products of
      the magnets was observed for iron. The composition of the microcosm plaques
      altered markedly between the two materials with less streptococci and more
      Veillonella spp. present in the biofilms grown on magnets in the presence of
      amalgam. The corrosion of neodymium-iron-boron magnets is limited and in the
      presence of amalgam is reduced further. This suggests that amalgam present in the
      mouth will not cause an increased clinical risk in terms of biocompatibility with
      neodymium-iron-boron magnets.

PMID- 14700269
TI  - Decontamination of tried-in orthodontic molar bands.
AB  - Molar bands are commonly used to retain orthodontic attachments on posterior
      teeth and due to the variation in the size of such teeth, it is usually necessary
      to 'try in' several bands before the correct one is selected. A possible concern
      with re-using such bands is the lack of cross-infection control, even following
      autoclaving, due to the presence of one or more small bore lumen (the archwire
      and headgear tubes). The aim of this experiment was, therefore, to determine
      whether such bands could be successfully decontaminated so that they could be re
      used without a cross-infection risk. Two hundred orthodontic molar bands that had
      previously been tried in patients' mouths, but not cemented into place, were
      tested. Each band was decontaminated using an enzymatic cleaner/disinfectant and
      then sterilized using either a downward displacement (n = 100) or a vacuum cycle
      autoclave (n = 100). Following autoclaving each band was inoculated into brain
      heart infusion culture broth and incubated at 37 degrees C for 5 days. None of
      the decontaminated bands exhibited growth after 5 days. It would appear that,
      using this methodology, there is little risk of a cross-infection hazard
      occurring with the re-use of previously tried-in and decontaminated molar bands.

PMID- 14700270
TI  - Acquisition of MHC-specific receptors on murine natural killer cells.
AB  - NK cells in adult mice express two families of MHC class I-specific receptors,
      namely, Ly49 and CD94/NKG2. Co-expression of these receptors in various
      combinations generates diverse receptor repertoires. The expression of individual
      receptors is mostly stochastic and independent of each other. NK cells acquire
      the receptors as they develop from progenitors in the bone marrow in adult mice.
      In vivo as well as in vitro studies have shown that the acquisition of the
      receptors is ordered and regulated by the host MHC class I. Developing NK cells
      first acquire CD94/NKG2 and subsequently various Ly49 receptors in an ordered
      manner. Unlike adult NK cells, most fetal and neonatal NK cells express CD94/NKG2
      but not Ly49. During the first several weeks after birth, NK cells expressing
      various Ly49 receptors slowly accumulate, while CD94/NKG2+ NK cells decrease to
      approximately 50% of the population. The acquisition of NK receptors following
      hematopoietic stem cell transplantation is also a slow and apparently
      preprogrammed process, mimicking the ontogeny, regardless of whether stem cells
      from fetal liver or adult bone marrow are used as donors. The regulation of the
      transcription of individual receptor genes is rather complex, since two promoters
      have been identified for the genes encoding Ly49 and CD94.

PMID- 14700271
TI  - Endothelial responses to bacterial toxins in sepsis.
AB  - The virulence of pathogenic bacteria is critically dependent on their ability to
      produce toxins that attack eukaryotic target cells. Microbial toxins are either
      structural components of the bacterial cell wall (endotoxins) or actively
      secreted proteins (exotoxins). Sepsis and septic shock, which represent major
      causes of mortality in modern intensive care medicine, are caused by an
      inadequate inflammatory and immunological host response to bacterial infection.
      Emerging evidence suggests that the systemic spread of microbial toxins, rather
      than bacteremia itself, is the crucial event in the pathogenesis of this dramatic
      dysregulation. The endothelium, with its diversity of physiological functions is
      a main target of bacterial toxins. The resulting endothelial dysfunction is
      believed to contribute to the underlying pathomechanisms and the collapse of
      homeostasis of organ function. In vitro, bacterial toxins induce subtle
      alterations of endothelial cell function rather than massive cell damage.
      Furthermore, bacterial toxins targeting endothelial cells severely alter the
      behavior of extravascular cells and circulating leukocytes via excessive
      formation of vasoactive mediators and overexpression of adhesion molecules.
      Research on the effects of microbial toxins on vascular endothelium has broadened
      our general understanding of microbial strategies to induce organ damage, even in
      the absence of viable bacteria. Combining antitoxin strategies with antibiotic
      therapy may prove to be of benefit to patients suffering from bacterial sepsis in
      the future.

PMID- 14700272
TI  - Tuning the rheostat of the myelopoietic system via Fas and TRAIL.
AB  - During the last decade, the concerted effort of numerous scientific groups has
      expanded our understanding of the finely tuned network present within bone marrow
      for the regulation of the hematopoietic system. This network, comprising humoral
      and cellular cross talk, is responsible for the adaptation of hematopoietic
      populations to demands as they arise. Major components of this control system are
      death receptors and their specific ligands, which eliminate superfluous cells
      once they have fulfilled their respective functions. The important role of Fas
      (CD95/Apo-1), one member of this death receptor family, in the regulation of T-
      and B-cell functions has been established. Alteration of Fas expression and/or
      function in lymphoid cells may contribute to the development of autoimmunity
      and/or neoplastic diseases. In addition to controlling lymphoid compartments, Fas
      is also involved in the regulation of myeloid cell functions. More recently,
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its specific
      receptors (TRAIL-R) have been identified as further members of this death
      receptor/ligand family. The TRAIL-R/TRAIL system is of vital importance for the
      maturation and functioning of immune effector cells of lymphoid, as well as
      myeloid, origin. In the present review, we have summarized current knowledge
      about both death receptor/ligand systems in the expansion and functioning of
      cells from the myeloid compartments, highlighted their role in normal
      hematopoiesis, and assessed their alterations in pathologic or neoplastic
      conditions.

PMID- 14700273
TI  - Is an improved measles-mumps-rubella vaccine necessary or feasible?
AB  - The measles-mumps-rubella (MMR) vaccine has been very effective in the
      elimination of disease and has high biosafety. However, it has been associated
      with several adverse effects and has recently caused controversy with regard to
      its possible association with inflammatory bowel disease and autism. This has
      been postulated to be a property of the measles component of the vaccine, and a
      "new variant" autism has recently been described and suggested to be associated
      with vaccine virus. Although one study has reported the presence of measles RNA
      in inflammatory bowel disease associated with autism, this has not been
      independently confirmed. This and most of the other demonstrated or perceived
      adverse effects of the MMR vaccine could theoretically be ascribed to its
      composition as a mixture of three live replicating viruses, one of which
      (measles) can induce immunosuppression, although this hypothesis is speculative.
      It may nonetheless be desirable to improve the biosafety of the MMR vaccine by
      the development of a nonreplicating vaccine that will stimulate efficient
      immunity and protection. DNA vaccines for measles, mumps, and rubella viruses
      have been constructed and tested in animal models but are poorly immunogenic.
      Several other prototype candidate vaccines are possible, including those based on
      the rubella virus component of the vaccine as a vector.

PMID- 14700274
TI  - Lanopylins A1, B1, A2 and B2, novel lanosterol synthase inhibitors from
      Streptomyces sp. K99-5041.
AB  - From an actinomycete strain, Streptomyces sp. K99-5041, lanopylins A1, B1, A2 and
      B2 were isolated as new natural products that inhibited the reaction of
      recombinant human lanosterol synthase. The crude extract from the whole broth of
      this strain was fractionated by silica gel column chromatography to afford an
      active fraction that showed a single spot on TLC. Detailed analyses of this
      fraction with liquid chromatography-atmospheric pressure chemical ionization mass
      spectrometry revealed that it contained 20 homologous compounds with differing
      side chain lengths. The fraction was separated by preparative HPLC to afford four
      of these homologues, lanopylins A1, B1, A2 and B2. Detailed spectroscopic
      analyses of these isolated compounds led to the identification of their
      structures. Lanopylins A1 and B1 were (3E)-isohexadecylmethylidene-2-methyl-1
      pyrroline and (3E)-hexadecylmethylidene-2-methyl-1-pyrroline, respectively, and
      lanopylins A2 and B2 were homologues with the insertion of one cis-ethylenylidene
      in the side chain of lanopylins A1 and B1, respectively. These compounds
      inhibited recombinant human lanosterol synthase with IC50 values of 15, 18, 33,
      and 41 microM, respectively.

PMID- 14700275
TI  - Cyrmenins, new beta-methoxyacrylate inhibitors of the electron transport.
      Production, isolation, physico-chemical and biological properties.
AB  - New antibiotic compounds, named cyrmenins, were isolated from the culture broth
      of strains of the myxobacteria Cystobacter armeniaca and Archangium gephyra. The
      compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are
      the first naturally occuring nitrogen-linked MOAs. The cyrmenins show nearly the
      same antifungal activity as strobilurin A, but are less toxic in a growth
      inhibition assay with L929 mouse cells. Cyrmenins inhibit NADH oxidation by
      submitochondrial particles from beef heart. Investigations by difference
      spectroscopy showed that cyrmenin B1 blocks the electron transport within the
      cytochrome bc1-segment (complex III) of the respiratory chain.

PMID- 14700276
TI  - SMTP-4D, -5D, -6D, -7D and -8D, a new series of the non-lysine-analog plasminogen
      modulators with a D-amino acid moiety.
AB  - Staplabin and SMTPs, triprenyl phenol metabolites of the fungus Stachybotrys
      microspora, are a family of non-lysine-analog plasminogen modulators that enhance
      both activation and fibrin binding of plasminogen by modulating plasminogen
      conformation. These compounds, including SMTP-4, -5, -6, -7 and -8, have an amino
      acid or an amino alcohol moiety in their structure, and precursor amine feeding
      greatly increases the biosynthesis of a metabolite of interest. In the present
      study, we have isolated five novel SMTPs (designated SMTP-4D, -5D, -6D, -7D and 
      8D) from precursor D-amino acid-fed cultures. Physico-chemical properties as well
      as chromatographic behavior were distinct from those of the corresponding L-amino
      acid analogs, which are selectively accumulated in L-amino acid-fed cultures and
      share common properties with corresponding natural products. The D-series SMTPs
      enhanced urokinase-catalyzed plasminogen activation by 10-fold at 80
      approximately 180 microM.

PMID- 14700277
TI  - Synthesis and biological activity of AM-112 and related oxapenem analogues.
AB  - Thirty five oxapenem analogues substituted with a range of tertiary groups at C-2
      have been synthesised and evaluated as broad-spectrum beta-lactamase inhibitors.
      All analogues enhanced the activity of ceftazidime against bacterial isolates
      producing Class A and Class C beta-lactamases. Compounds with cyclic substituents
      at C-1' (attached to C-6) were associated with enhanced antibacterial activity
      against Staphylococcus aureus. (R) Stereochemistry at C-1' led to synergistic
      activity against beta-lactamase negative enterococci. (S) Stereochemistry at C-1'
      was associated with enhanced inhibition of Class A beta-lactamases and lack of
      synergistic activity against enterococci. AM-113 was unstable in serum and not
      detectable following subcutaneous or oral dosing in mice. AM-112 and AM-115
      achieved good serum levels following subcutaneous dosing. AM-114 exhibited 30%
      bioavailability following oral dosing. AM-112 [(1'R,5R,6R)-2-(4-ammonio-1,1
      dimethylbutyl)-6-(1'-hydroxyethyl)oxapenem-3-carboxylate] achieved the greatest
      protection of ceftazidime against Gram-negatives producing Class A or C beta
      lactamases.

PMID- 14700278
TI  - Milbemycin alpha17 and related compounds synthesized from milbemycin A4:
      synthetic procedure and acaricidal activities.
AB  - Milbemycin alpha17, a 14-demethyl congener of milbemycin A4, has been reported as
      a natural product. In this paper, we report the successful development of a
      chemical derivation method to synthesize milbemycin alpha17 from milbemycin A4,
      as well as our use of a similar method to prepare 24-demethylmilbemycin A4 from
      the same precursor. The acaricidal activities of these compounds were assessed
      against the organophosphorus-sensitive two-spotted spider mites (Tetranychus
      urticae) on the primary leaves of cowpea plants (Vigna sinesis Savi species) by
      spraying.

PMID- 14700279
TI  - New cytotoxic bafilomycin C1-amide produced by Kitasatospora cheerisanensis.

PMID- 14700280
TI  - Isolation and identification of cissetin--a setin-like antibiotic with a novel
      cis-octalin ring fusion.

PMID- 14700281
TI  - Planar structure and antibacterial activity of korormicin derivatives isolated
      from Pseudoalteromonas sp. F-420.

PMID- 14700282
TI  - Pseudoalterobactin A and B, new siderophores excreted by marine bacterium
      Pseudoalteromonas sp. KP20-4.

PMID- 14700283
TI  - Enhanced production of fattiviracins by bacitracin-resistant strains of
      Streptomyces microflavus strain No. 2445.

PMID- 14700284
TI  - Early versus delayed fixation of pelvic ring fractures.
AB  - This retrospective study reports outcomes, after early and delayed surgical
      stabilization of fractures of the pelvic ring, in terms of pulmonary
      complications, length of hospital stay, and cost of hospitalization. The hospital
      course of 151 patients admitted to an academic teaching hospital who sustained
      acute fractures of the pelvic ring between June 1996 and December 2000 was
      reviewed. Patient demographics, Injury Severity Score (ISS), timing of operative
      fixation, and the incidence of pulmonary complications were analyzed. Radiographs
      were reviewed and fractures classified according to the modified Tile system.
      Tile fracture types B and C patients who underwent fixation within 1 week of
      injury (n = 71) were compared to those in whom surgery was delayed (n = 28).
      Adjusting for the ISS, early-repair patients had a lower risk of pulmonary
      complications (RR = 0.49, 95% CI = 0.25-0.96), a reduced length of hospital stay
      (12.2 vs. 20.5 days; P = 0.0005), and overall reduced cost of care (57,084
      dollars vs. 158,625 dollars; P = 0.0317). Pelvic ring fixation within the first
      week of injury results in significantly reduced incidence of pulmonary
      complication, hospital stay, and cost of care regardless of injury severity. The
      coordinated team approach to insure prompt resuscitation, stabilization, and
      operative fixation results in more optimal patient outcomes.

PMID- 14700285
TI  - Early one-stage closure in patients with abdominal compartment syndrome: fascial
      replacement with human acellular dermis and bipedicle flaps.
AB  - Decompressive celiotomy for the treatment of abdominal compartment syndrome (ACS)
      often results in wounds that are difficult to close. These complicated wounds are
      frequently managed with a 3-staged surgical approach employing a planned ventral
      hernia. The authors describe an alternative closure with a single operation using
      a commercially available human acellular dermis (HACD) as a fascial substitute.
      Soft tissue coverage is obtained at the same operation by means of bilateral
      bipedicle flaps. The cohort consisted of 9 patients, ages 19 to 77 years old. On
      average patients were closed on the ninth postoperative day (range, 3 to 30 days)
      and were discharged from the trauma center on average 8 days (range, 5 to 29
      days) after the abdominal closure. Complications developed in 3 (33%) patients.
      These complications included a flap hematoma, wound infection, and recurrent
      hernia. There were no postoperative fistulas. This procedure allows for early,
      single-staged closure of the abdomen after abdominal compartment syndrome. Once
      closed, patients were able to be discharged from the hospital early and without
      need for specialized wound care. Further investigation on the usefulness of this
      technique is required.

PMID- 14700286
TI  - Use of a vacuum-assisted device to facilitate abdominal closure.
AB  - The inability for abdominal closure in critically ill surgical patients provides
      a complex problem. Often, these patients are left with a large ventral hernia,
      which requires readmission for abdominal wall repair. We are reporting on the use
      of a vacuum-assisted device (VAD) to facilitate abdominal wall closure. Fifteen
      patients were enrolled for placement of a VAD. Selection was based on the
      diagnosis of abdominal compartment syndrome, the inability for abdominal closure
      at the initial operation, or the inability to close the abdomen upon re
      exploration. Ten (67%) patients were successfully closed within 11 days using the
      VAD. Predictors of successful closure were the duration of VAD placement (< 12
      days, P < 0.001), the total amount of VAD output (< 3 L, P < 0.04), the patient's
      cumulative fluid balance within the first 2 weeks (< 2 L, P < 0.002), or the
      presence of a systemic infection at the time of attempted closure (P < 0.001).
      After 6 months, there have been no complications in patients successfully closed
      with this device. There have been a few recent reports describing VAD abdominal
      closures. While not successful for every case, the majority of our patients were
      able to have their abdominal wall closed primarily. We plan to use this technique
      to help shorten hospital stay and prevent readmission for hernia repair.

PMID- 14700287
TI  - Air following splenic embolization: infection or incidental finding?
AB  - The use of splenic embolization for nonoperative management has increased. With
      increased use of this adjunct, a new and frequent finding has been air within the
      areas of infarction in patients with or without clinical signs of infection. The
      purpose of this study was to determine if air within areas of splenic infarction
      is pathologic of infection or rather an incidental finding. A retrospective
      review over the past 3 years of inpatients undergoing splenic embolization and
      having pre- and postembolization abdominal computed tomography scans were
      reviewed for the findings of free air as well as any clinical signs of infection.
      A total of 96 consecutive patients were included. Of these, 12 had evidence of
      infarction with air. Six of these patients had undergone distal embolization with
      intraparenchymal air, but no symptoms. These were successfully observed. Two
      patients demonstrated subcapsular air/fluid levels, which underwent drainage with
      splenic preservation. Cultures were negative for infection. The remaining 4
      underwent splenectomy. Of these, all had large collections of air. Two of these 4
      spleens were infected: 1 with alpha-hemolytic Streptococcus and one with
      Clostridia perfringens. The remainder was sterile. This gave an overall infection
      rate of 17 per cent of patients with evidence of air. This yield increased to 33
      per cent if the patient had symptoms and 50 per cent in those with large amounts
      of air and symptoms. Overall, we feel that air following embolization is a
      concern, but does not constitute infection. Patients with large amounts of air
      and signs and symptoms of infection will have a far higher infectious rate, 50
      per cent in this limited series. In these patients, evaluation for infection is
      indicated; that being percutaneous sampling versus splenectomy.

PMID- 14700288
TI  - Outcome after lateral pancreaticojejunostomy in patients with chronic
      pancreatitis associated with pancreas divisum.
AB  - In order to evaluate surgical outcome after lateral pancreaticojejunostomy (LPJ)
      in patients with pancreas divisum (PD), we compared the operative results in
      patients who underwent LPJ for PD with those who underwent LPJ for other causes
      of chronic pancreatitis. The records of 129 patients who underwent LPJ for
      chronic pain associated with chronic pancreatitis from 1995 through 2001 were
      retrospectively reviewed and analyzed. There were 21 patients (11 men, 10 women,
      mean age 40 years) who had PD as a cause of chronic pancreatitis. The remaining
      108 patients (58 men, 50 women, mean age 48 years) had chronic pancreatitis of
      other etiologies. The two groups had a similar stage of disease progress measured
      by incidence of pancreatic duct strictures, terminal biliary stenosis,
      pseudocysts, insulin dependency, need for pancreatic enzymes, and symptom
      duration. There was no difference in operative time (200 +/- 13.3 vs. 206 +/- 6.1
      minutes) or intraoperative blood loss (200 vs. 300 mL) comparing the PD to the
      other group. The overall postoperative morbidity (14% vs. 23%) and mortality (0%
      vs. 2%) were not significantly different in PD versus other group comparison.
      Hospital length of stay was similar in both groups (7.0 +/- 2.4 vs. 8.0 +/- 1.3
      days). In the PD group 10 per cent required reoperation with pancreatic resection
      for failure of LPJ to improve chronic pain versus 9 per cent in the other group.
      Comparison of patients who undergo LPJ for PD with those who undergo LPJ for
      other etiologies showed no significant difference in failure rates as measured by
      the need for reoperation. Postoperative morbidity and mortality were similar in
      both groups. Failure of LPJ in patients with PD may be related to factors
      associated with failure of LPJ in management of chronic pancreatitis of other
      causes. This includes inadequate drainage of the head of gland, failure to drain
      small ducts, and perineural inflammation.

PMID- 14700289
TI  - The presence of colorectal hepatic metastases does not preclude pulmonary
      metastasectomy.
AB  - Hepatic metastases due to colorectal carcinoma have often been felt to preclude
      pulmonary metastasectomy. With the recent advances in surgical options, should
      patients with both liver and lung metastases be considered for surgical
      resection? The current study reviews the impact of such aggressive management on
      disease-free and overall survival (OS). The clinical course of 63 patients
      presenting with colorectal metastasis to the lung alone (group 1, n = 45) or
      combined hepatic and lung metastases (group 2, n = 18) were reviewed. All
      patients underwent complete resection of their lung metastases. Surgical control
      of hepatic tumor burden was achieved by tumor ablation, intra-arterial therapy,
      and/or resection. All patients in group 1 and group 2 were available for a mean
      follow-up of 27 and 24 months, respectively. The presence of hepatic metastases,
      the resectability of hepatic tumor burden, and the disease-free interval after
      pulmonary metastasectomy did not significantly influence survival. These findings
      demonstrate that aggressive surgical management of pulmonary metastases in the
      presence of liver metastases offers a similar benefit as compared to patients
      with pulmonary metastases alone. Therefore, hepatic metastatic disease does not
      preclude an attempt at pulmonary metastasectomy if hepatic metastases can be
      resected or remains responsive to therapy. Such an approach achieves comparable
      OS and mean survival when compared to pulmonary metastasectomy alone.

PMID- 14700290
TI  - Comparison of wound-healing characteristics with feedback circuit electrosurgical
      generators in a porcine model.
AB  - The type of incisional instrument used to create a surgical wound can influence
      the rate of wound healing and overall wound strength. The purpose of this study
      was to evaluate several facets of wound healing within incisions created in the
      small intestine, uterus, and skin in a porcine model by using feedback circuit
      electrosurgical generators and a standard steel scalpel blade in a porcine model.
      Eighteen pigs were evaluated by creating surgical incisions in the skin, uterus,
      and small intestine utilizing 2 computerized electrosurgical generators (FX,
      ValleyLab, Boulder, CO, and PEGASYS, Ethicon Endo-Surgery, Inc., Cincinnati, OH)
      and a scalpel blade. All incisions were reapproximated with absorbable suture.
      Incision sites were evaluated histologically at 3, 7, or 14 days postincision
      according to randomization. The skin and small intestine samples were tested for
      wound tensile strength at 7 and 14 days. There were no statistically significant
      differences demonstrated with tensile strength testing comparing the
      electrosurgical devices to the scalpel-blade incisions for skin or small
      intestine at all time points. The only significant difference detected with
      respect to wound tensile strength was when different organ types were compared,
      regardless of device used (i.e., skin, 19.5 N/cm2 vs. small intestine, 5.78
      N/cm2). Histologic evaluation demonstrated that the wounds created by the
      electrosurgical generators displayed decreased overall wound healing at 3, 7, and
      14 days compared to the scalpel group. These findings indicate that the
      electrosurgical devices tested delay wound healing at the surgical site, but fail
      to demonstrate any significant difference in overall wound tensile strength.
      Wound healing may occur at a more rapid rate when a traditional scalpel blade is
      used to create the surgical incision, but no difference in global wound dynamics
      could be detected.

PMID- 14700291
TI  - Hand-assisted surgery improves outcomes for laparoscopic nephrectomy.
AB  - Laparoscopy has become the preferred method for nephrectomy in many medical
      centers. We compared our experience with hand-assisted laparoscopic nephrectomy
      (HALN) and standard laparoscopic nephrectomy (LN). Data were prospectively
      collected on 119 consecutive patients undergoing laparoscopic nephrectomy between
      August 2000 and November 2002. Outcomes were compared for LN versus HALN using
      Wilcoxon rank sum test for quantitative outcomes and Fisher exact test and chi2
      for qualitative outcomes. Thirty-nine patients underwent LN: 16 live donor, 16
      radical, and 7 simple nephrectomies. Eighty patients were treated with HALN: 47
      live donor, 32 radical, and 1 simple nephrectomy. There were no differences in
      mean age (49.2 years LN vs. 47.7 years HALN, P = 0.60) or weight (192.2 lb LN,
      179.2 lb HALN, P = 0.12). Mean tumor size (4.77 cm LN vs. 7.12 cm HALN, P = 0.07)
      and length of extraction incision (8.37 cm LN vs. 7.87 cm HALN, P = 0.08) were
      similar. Total hospital charges (19,352 dollars vs. 18,505 dollars, P = 0.29) and
      length of stay (3.68 days vs. 3.72 days, P = 0.15) were equivalent for LN and
      HALN. Average operative time for HALN was significantly shorter (202 minutes vs.
      258 minutes, P = 0.0001), and blood loss was less for HALN (71.7 cc vs. 113.1 cc,
      P = 0.007). Wound complications rates were similar (6.5% HALN vs. 13% LN, P =
      0.34), but overall morbidity rates were higher after LN (28.2% vs. 6.3%, P =
      0.001). Compared with pure laparoscopic nephrectomy, the hand-assisted approach
      reduces operative time and blood loss without increasing total hospital charges
      or length of stay. In our patients, HALN was also associated with fewer
      postoperative complications than standard laparoscopic nephrectomy. Hand-assisted
      laparoscopy may allow for the performance of increasingly complex procedures
      while maintaining the benefits of minimally invasive surgery.

PMID- 14700292
TI  - Radio-frequency ablation in cirrhotic patients with hepatocellular carcinoma.
AB  - Current surgical treatments for hepatocellular carcinoma (HCC) include radio
      frequency ablation (RFA), resection, and orthotropic liver transplant (OLT). RFA
      is particularly attractive in these high-risk patients because surgery is
      associated with high mortality and there is a relative scarcity of organs
      available for those in need of transplants. This study was performed to evaluate
      the management of cirrhotic patients with HCC undergoing RFA at a single Western
      institution. A retrospective study from March 1999 to June 2002 was performed to
      evaluate the clinicopathologic and treatment-related variables in cirrhotic
      patients with HCC. Forty-nine lesions in 26 patients with HCC and cirrhosis
      underwent RFA. Data was analyzed for safety and overall survival as the main
      endpoints. The mean age was 60.4 +/- 11 years, 19 patients were male, 5 had
      hepatitis B virus, and 19 had hepatitis C virus. The Child classification was 26
      per cent, 39 per cent, and 35 per cent for A, B, and C; the number of lesions was
      1 in 62 per cent, 2 in 23 per cent, and more than 2 in 15 per cent. The approach
      was laparoscopic in 58 per cent, percutaneous in 15 per cent, and open in 27 per
      cent. There were no mortalities and only 1 complication. Average hospital stay
      was 2.7 +/- 2 days. Subsequent to RFA, 9 patients underwent an OLT within a
      median of 4.1 months. The median follow-up of the whole group was 13 months and
      the disease-free survival 9.3 months. Tumor recurrence was identified in 3
      previously ablated lesions, nonablated liver in 11, and as pulmonary metastases
      in 3. Overall survival (P = 0.03) was prolonged for those treated with RFA + OLT
      over RFA alone. We conclude that RFA is a safe ablative technique in high-risk
      cirrhotic patients with HCC. This technique may provide a bridge to OLT; however,
      it remains to be proven whether it prolongs survival in those who do not undergo
      OLT.

PMID- 14700293
TI  - Laparoscopic omental harvest for flap coverage in complex mediastinitis.
AB  - Mediastinitis is one of the most serious complications of cardiac surgery. The
      standard of care in mediastinitis includes thorough sequential debridement, flap
      coverage, and culture-directed antibiotics. The most frequently utilized muscles
      for flap reconstruction include the rectus abdominus and the pectoralis major.
      However, in some instances these flaps may be inadequate, unavailable, or fail,
      thus requiring an alternative choice or adjuvant. Most coronary graft procedures
      utilize the left internal mammary artery, frequently eliminating the left rectus
      muscles, while prior open cholecystectomy patients frequently lose availability
      of their right rectus muscle. In addition, radiation therapy or prior flap
      failure may exclude other muscle transfer procedures. The omentum offers
      excellent coverage due to mobility and superb arterial and lymphatic flow.
      Unfortunately, in the past, this has required a celiotomy in an already
      critically ill patient. We present a series of 5 patients where the omentum was
      mobilized laparoscopically and passed through an anterior diaphragmatic incision.
      This option spares a celiotomy, seals the wound, and hastens recovery in very ill
      patients. We also present a complete review of literature on the topic and
      provide an algorithm for complex sternal wound reconstruction.

PMID- 14700294
TI  - Malignant duodenal somatostatinoma presenting in association with von
      Recklinghausen disease.
AB  - Somatostatinomas are extremely rare periampullary malignant neuroendocrine tumors
      that may be associated with von Recklinghausen disease or type-I
      neurofibromatosis. Duodenal somatostatinomas are distinguished from pancreatic
      somatostatinomas by their frequent association with type-I neurofibromatosis and
      typically absence of somatostatinoma syndrome. We report a very rare and atypical
      case of malignant duodenal somatostatinoma presenting with somatostatinoma
      syndrome in association with type-I neurofibromatosis.

PMID- 14700295
TI  - Primary insertion of a silastic spring-loaded silo for gastroschisis.
AB  - Gastroschisis is traditionally managed by emergency primary closure, with a
      temporary silo reserved for large defects unable to be closed primarily. We
      recently have begun primary Silastic (Dow Coming, Midland, MI) spring-loaded silo
      (SLS) closure followed by elective closure and report our preliminary experience.
      A total of 15 infants (weight range, 2.1-13.5 kg) at 2 different institutions
      were treated by SC by 3 different surgeons between 1998 and 2002. A 3-, 4-, or 5
      cm (ring diameter) silo was used depending on size of abdominal wall defect.
      Elective closure was performed in the operating room or at the bedside. Surgical
      parameters assessed included success of SLS, peak inspiratory pressures (PIPs)
      pre- and post-SLS closure, total time of staged closure with SLS, time to full
      feedings, and intra- and postoperative complications. Fifteen of 15 infants were
      successfully treated by SLS closure followed by elective closure. Two of 15
      (13.3%) experienced temporary dislodgement of the silo prior to permanent
      closure. In both cases, the silo was safely reinserted at the bedside. Comparison
      of PIP values measured at various stages of SLS closure revealed no significant
      difference (P > 0.05). Mean times to final fascial closure (3.7 days) and full
      enteral feedings (22 days) were similar to historical controls obtained from the
      surgical literature. In 1 case where there was associated intestinal atresia, SLS
      closure was effective in permitting concomitant elective closure and re
      establishment of bowel continuity. All children are alive and well at the time of
      this report. SLS closure permits safe, gentle, and gradual reduction of the
      exposed viscera leading to successful permanent abdominal wall closure.
      Respiratory embarrassment and hemodynamic instability associated with emergent
      (primary) closure of large abdominal wall defects can thus be avoided.

PMID- 14700296
TI  - Thoracoscopic thymectomy in children with myasthenia gravis.
AB  - Although conservative medical management is the mainstay in the treatment of
      myasthenia gravis (MG), severest forms of the disease often require surgical
      thymectomy. Thoracoscopic thymectomy (TT) represents a minimally invasive
      alternative to traditional thymectomy via sternotomy. We present our preliminary
      experience with TT as definitive treatment for severe forms of MG. The charts of
      5 children (4 girls and 1 boy; age range, 11-17 years) who underwent TT for MG
      were retrospectively reviewed. TT was typically performed via left thoracoscopy
      using 4- or 5-mm ports with 1 of the ports enlarged at the end of the procedure
      for specimen retrieval. Thymic veins were identified and ligated with surgical
      clips in all cases. Surgical parameters assessed were the following: operating
      time, intra- and postoperative complications, length of postoperative stay, and
      resolution of symptoms. Follow-up ranged from 6 months to 2 years. All 5 TTs were
      successfully completed. In 1 case, right-sided thoracoscopy was added to ensure
      complete gland excision. Surgical pathology in all cases demonstrated complete
      excision. Mean operating time was 121 minutes (range 88 minutes to 188 minutes).
      There were no intra- or postoperative complications. Length of postoperative stay
      averaged 1.6 days (range, 1 to 3 days). Four of 5 (80%) had clear resolution of
      symptoms with 1 showing minimal resolution at 6 months. Thoracoscopic thymectomy
      is a safe and potentially attractive alternative to traditional thymectomy via
      median sternotomy in severe forms of myasthenia gravis. Complete thymectomy, the
      goal of traditional surgical treatment for myasthenia gravis, can effectively by
      achieved via this minimally invasive technique.

PMID- 14700297
TI  - Minimally invasive parathyroidectomy: how effective is preoperative sestamibi
      scanning?
AB  - Minimally invasive parathyroidectomy (MIP) guided by preoperative sestamibi
      scanning has been shown to reduce operative time, hospital stay, and cost in
      treating primary hyperparathyroidism. However, controversy exists over routine
      preoperative sestamibi scanning. The purpose of this study was to determine the
      utility of sestamibi scanning at our institution as part of the MIP protocol and
      to analyze calcium and parathyroid hormone levels as possible predictors of
      successful sestamibi scanning. Charts of 37 consecutive patients undergoing MIP
      at our institution were reviewed, and age, sex, preoperative calcium, and
      parathyroid (PTH) levels, invasiveness of procedure, and pathologic diagnosis
      were recorded. Sestamibi scans were reviewed and scored by 4 nuclear medicine
      faculty based on the level of suspicion for parathyroid adenoma. Neither calcium
      nor PTH correlated significantly with sestamibi scan score (Spearman coefficient,
      r = 0.075, P = 0.67 and r = 0.277, P = 0.10, respectively). Receiver-operating
      characteristic (ROC) analysis showed sestamibi scanning to have sensitivity and
      specificity in predicting MIP completion (87% and 68%). Logistic regression
      showed only sestamibi scan (P = 0.038), not calcium or PTH (P = 0.977 and P =
      0.767) to be predictive of MIP completion. In conclusion, sestamibi scanning
      effectively predicted the ability to perform MIP. However, preoperative calcium
      and PTH predicted neither sestamibi scan results nor completion of MIP.

PMID- 14700298
TI  - Injuries in pediatric patients with seatbelt contusions.
AB  - Children restrained with lap belts may sustain severe injuries. We investigated
      the frequency of each type of injury associated with seatbelt contusions. The
      medical records of all trauma patients with ICD-9 codes for abdominal wall
      contusions from January 1, 1999, to December 31, 2001, were reviewed. All
      patients with seatbelt contusions were included in the study. Age, seat position,
      weight, restraint-type, sex, and mechanism of injury were noted. There were 1447
      admissions for trauma over the 3-year period. Forty-six patients (ages 4-13) had
      a seatbelt contusion. Thirty-three wore lap belts, and 13 wore lap and shoulder
      harnesses. Twenty-two children required abdominal exploration. Small bowel
      injuries were the most common intra-abdominal injuries. Facial injuries were the
      most common associated injuries. Forty-eight per cent of children with seatbelt
      contusions in our institution required surgery. The smaller patients tend to have
      higher frequency of abdominal injuries. The presence of seatbelt contusion
      indicates the possibility of severe internal injuries.

PMID- 14700299
TI  - HER2 expression in thyroid tumors.
AB  - Similarities exist in hormone receptors of breast, prostate, and thyroid tumors.
      HER2 oncogene expression is known to be present in breast and prostate tumors,
      but conflicting data have been published about its presence in thyroid tumors.
      This uncertainty prompted us to examine the incidence of HER2 overexpression in
      normal and malignant thyroid tissue. Normal and neoplastic thyroid tissue samples
      from 46 female and 9 male patients were assayed for HER2 expression by
      immunohistochemical assay. Of the 55 total samples, 36 were from neoplasms and 19
      were from benign tissues. Significant HER2 overexpression was not found in any
      benign or malignant thyroid tissue. Two of 6 thyroid carcinomas from male
      patients showed 1+ reactivity for HER2 expression on immunohistochemistry assay,
      but remained negative on fluorescene in sito hybridization confirmatory testing.
      No significant expression of HER2 was noted in benign or malignant thyroid
      tissue. These results cast doubt on the value of HER2 as a prognostic factor or
      possible target for specific antitumor therapy for thyroid cancer.

PMID- 14700300
TI  - Improved results using ultrasound guidance for central venous access.
AB  - Central venous cannulation is an essential part of patient management in a
      variety of clinical settings. The complications of cannulation may be as high as
      10 per cent and include arterial puncture, pneumothorax, hemothorax, cardiac
      tamponade, hematoma, malposition of catheter, nerve injury, and death. Standard
      technique for placement of central venous catheters is by use of a blinded,
      external landmark-guided technique. Success rates and complication rates vary
      according to the technique employed. Ultrasound use in general surgery has gained
      popularity and is now readily available in most operating suites. A prospective
      study was conducted to evaluate the feasibility of ultrasound-guided placement of
      central venous access devices. Ultrasound guidance was used to place central
      venous ports for chemotherapy in 29 patients. Catheters were placed using a
      handheld ultrasound (7.5 MHz, linear probe, Aloka, Wallingford, CT) with the
      Seldinger technique. The internal jugular vein was used as the primary site.
      Accurate placement within the superior vena cava was confirmed with fluoroscopy.
      All procedures were performed under local anesthesia with intravenous sedation.
      The data analyzed included length of procedure, complications, and success rates.
      The right internal jugular vein was used in all but 4 of our patients. In 2 of
      those patients, the left internal jugular was chosen initially. In the other 2,
      anatomical variants were discovered requiring a modification of technique to
      cannulate the right internal jugular vein. Overall, ultrasound led to a change in
      management in 14 per cent of patients. The average time for placement was 30
      minutes (range, 22-42 minutes). There were no failures in placement or
      misplacement of the catheters. Detection of anatomy prior to venipuncture and
      direct real-time visualization are the keys to success with ultrasound guidance.
      This study shows that placement of central venous catheters, using ultrasound
      guidance, may be done in a timely manner while minimizing risks and maximizing
      success.

PMID- 14700301
TI  - Thoracotomy for blunt trauma: traditional indications may not apply.
AB  - The indications for performing as urgent thoractomy after trauma are based on the
      criteria used for penetrating injuries. However, few data are available on the
      use of these indications for patients with blunt injuries. In a retrospective
      study (June 1996 to July 2001), we compared the indications of urgent thoracotomy
      after blunt injury and penetrating injury in patients who underwent thoracotomy
      within 24 hours of hospital admission at our institution. Patients with blunt
      aortic injuries or emergency department thoracotomies were excluded from
      evaluation. Fifty-nine patients were identified (37 penetrating injuries, 22
      blunt injuries). Blunt trauma victims had a higher mortality rate than
      penetrating trauma victims (73% vs. 22%). Chest tube output was the indication
      for nontherapuetic thoracotomy in 5 patients with blunt injuries whereas this
      occurred in only 1 penetrating injury victim (P = 0.04). All 5 blunt injury
      patients underwent a prior procedure and were coagulopathic when thoracotomy was
      performed. In conclusion, thoracotomy following blunt trauma is associated with a
      high rate of mortality. The rate of nontherapeutic exploration is increased when
      chest tube output is the indication for thoracotomy after blunt trauma. Since the
      majority of such patients have multicavitary injuries that require prior
      operation and are commonly coagulopathic, caution should be exercised when
      deciding whether to proceed with thoracotomy based solely on chest tube output.

PMID- 14700302
TI  - Assessment of individual hand performance in box trainers compared to virtual
      reality trainers.
AB  - Training residents in laparoscopic skills is ideally initiated in an inanimate
      laboratory with both box trainers and virtual reality trainers. Virtual reality
      trainers have the ability to score individual hand performance although they are
      expensive. Here we compared the ability to assess dominant and nondominant hand
      performance in box trainers with virtual reality trainers. Medical students
      without laparoscopic experience were utilized in this study (n = 16). Each
      student performed tasks on the LTS 2000, an inanimate box trainer (placing pegs
      with both hands and transferring pegs from one hand to another), as well as a
      task on the MIST-VR, a virtual reality trainer (grasping a virtual object and
      placing it in a virtual receptable with alternating hands). A surgeon scored
      students for the inanimate box trainer exercises (time and errors) while the MIST
      VR scored students (time, economy of movements, and errors for each hand).
      Statistical analysis included Pearson correlations. Errors and time for the one
      handed tasks on the box trainer did not correlate with errors, time, or economy
      measured for each hand by the MIST-VR (r = 0.01 to 0.30; P = NS). Total errors on
      the virtual reality trainer did correlate with errors on transferring pege (r =
      0.61; P < 0.05). Economy and time of both dominant and nondominant hand from the
      MIST-VR correlated with time of transferring pegs in the box trainer (r = 0.53 to
      0.77; P < 0.05). While individual hand assessment by the box trainer during 2
      handed tasks was related to assessment by the virtual reality trainer, individual
      hand assessment during 1-handed tasks did not correlate with the virtual reality
      trainer. Virtual reality trainers, such as the MIST-VR, allow assessment of
      individual hand skills which may lead to improved laparoscopic skill acquisition.
      It is difficult to assess individual hand performance with box trainers alone.

PMID- 14700303
TI  - Let the sunshine in.

PMID- 14700304
TI  - GM crops may harm biodiversity.

PMID- 14700305
TI  - Asbestos investigation under way.

PMID- 14700306
TI  - Will fish farms feed the world?

PMID- 14700307
TI  - Biopolymer removes mercury from wastewaters.

PMID- 14700308
TI  - Applying the principles of Green Engineering to cradle-to-cradle design.

PMID- 14700309
TI  - Success through collaboration.

PMID- 14700310
TI  - EcoWorx, Green Engineering principles in practice.
AB  - The 12 Principles of Green Engineering have been proposed as a framework within
      which to examine existing products and guide their redesign as well as to
      evaluate new product designs. The EcoWorx system represents a recyclable carpet
      tile product that is assessed using the 12 Principles of Green Engineering and
      cradle-to-cradle design principles to evaluate environmental, qualitative, and
      economic performance as compared to existing Shaw carpet tile products. The
      product design strategy embodies life cycle considerations of a cradle-to-cradle
      product that puts technical nutrient recovered materials into repeated use.
      EcoWorx offers a unique opportunity for Shaw to utilize the 12 Principles to
      analyze and optimize new products and processes for the additional capacity
      needed to meet rising demand for sustainable carpet products. The analysis of the
      EcoWorx system demonstrated the value of the 12 Principles in verifying and
      formalizing the experience and intuition of product designers. This suggests that
      the mistrial and error reliance on experience could be enhanced with this
      formalized approach and hence lead to more widespread success of design practices
      that result in sustainable products.

PMID- 14700311
TI  - Design of hard water stable emulsifier systems for petroleum- and bio-based semi
      synthetic metalworking fluids.
AB  - Metalworking fluids (MWFs) increase productivity and the quality of manufacturing
      operations by cooling and lubricating during metal forming and cutting processes.
      Despite their widespread use, they pose significant health and environmental
      hazards throughout their life cycle. An obvious environmental improvement to MWF
      technology would be to improve the lifetime of the fluid while utilizing more
      environmentally friendly and less energy-consuming materials without compromising
      existing performance levels. This investigation focuses on the design of mixed
      anionionc:nonionic emulsifier systems for petroleum and bio-based MWFs that
      improve fluid lifetime by providing emulsion stability under hard water
      conditions, a common cause of emulsion destabilization leading to MWF disposal.
      Experimental conditions were designed to evaluate the impact of emulsifier
      structural characteristics (straight chain, branched tail, branched head) and the
      molar ratios of anionic to nonionic surfactant and oil to total surfactant.
      Results from the 2500 formulations generated indicate that the use of a twin
      headed anionic surfactant can provide improved hard water stability for both
      mineral oil- and vegetable oil-based formulations, even in the absence of a
      chelating agent and a coupler. Results also suggest that an oil:total surfactant
      molar ratio of 0.5 or less is necessary for particle size stability in hard water
      conditions for these systems. The newly developed petroleum and bio-based
      formulations with improved hard water stability are competitive with commercially
      available MWFs in performance evaluations for tramp oil rejection, contact angle,
      and tapping torque efficiency. These results can be used to design MWF
      formulations with fewer components and extended lifetime under hard water
      conditions, both of which would lead to a reduction in the life cycle
      environmental impact of MWFs.

PMID- 14700312
TI  - Oxidation reactions in CO2: academic exercise or future green processes?
AB  - Conducting oxidation reactions using CO2 as the solvent is a promising strategy
      for creation of greener chemical processes that are also economical, as CO2 and
      water are probably the only solvents that can be used in oxidation reactions
      without the formation of any solvent byproducts. However, it must be noted that
      the promise of CO2-based oxidation still dwarfs the actual realization of CO2
      based oxidation processes. Nevertheless, there is extensive literature on the use
      of CO2 as the solvent for the oxidation of cyclohexane (adipic acid synthesis),
      cumene oxidation (phenol synthesis), and epoxidation (propylene oxide synthesis).
      In all of these studies, knowledge of the phase behavior is crucial toward
      understanding the effects of pressure and temperature on reaction outcomes. To
      date, much of the research in this field has involved simply using CO2 as a "drop
      in" replacement for a conventional organic solvent; it will be interesting in the
      future to see if the use of CO2 can be combined with innovations in catalyst and
      reactor design to create truly green oxidation processes where the use of CO2 is
      not merely tolerated but truly supports process and chemistry innovation.

PMID- 14700313
TI  - Product self-management: evolution in recycling and reuse.
AB  - This paper explores the potential to make product recycling and reuse easier by
      shifting responsibility for product management toward the product itself.
      Examples range from barcode-enabled Internet sales of used products to RFID
      enabled garbage trucks that identify recyclable items and provide rebates.
      Initial steps toward product self-management have made opportunistic use of
      product bar codes and Internet markets. In the United States, Internet markets
      are driving increased reuse of products. In the European Union, recycling and
      waste management policy is driving the use of radio electronics in waste
      management. Prospects for product self-management are assessed from both a
      technological and an economic perspective. The technological analysis indicates
      that radio-frequency tags offer some advantages over bar codes, but their
      application to product self-management requires considerable investment in the
      waste management infrastructure. This suggests that early applications of
      advanced product tags are most suitable for Germany and other countries where the
      waste management industry has already integrated information technology into its
      operations. The economic analysis indicates that increased reuse of products can
      reduce consumption of new products and materials, although on a less than one-to
      one basis, simultaneously reducing costs for consumers and deriving more value
      from existing products.

PMID- 14700314
TI  - Multi-criteria decision-making for optimization of product disassembly under
      multiple situations.
AB  - With growing interest in recovering materials and subassemblies within consumer
      products at the end of their useful life, there has been an increasing interest
      in developing decision-making methodologies that determine how to maximize the
      environmental benefits of end-of-life (EOL) processing while minimizing costs
      under variable EOL situations. This paper describes a methodology to analyze how
      product designs and situational variables impact the Pareto set of optimal EOL
      strategies with the greatest environmental benefit for a given economic cost or
      profit. Since the determination of this Pareto set via enumeration of all
      disassembly sequences and EOL fates is prohibitively time-consuming even for
      relatively simple products, multi-objective genetic algorithms (GA) are utilized
      to rapidly approximate the Pareto set of optimal EOL trade-offs between cost and
      environmentally conscious actions. Such rapid calculations of the Pareto set are
      critical to better understand the influence of situational variables on how
      disassembly and recycling decisions change under different EOL scenarios (e.g.,
      undervariable regulatory, infrastructure, or market situations). To illustrate
      the methodology, a case study involving the EOL treatment of a coffee maker is
      described. Impacts of situational variables on trade-offs between recovered
      energy and cost in Aachen, Germany, and in Ann Arbor, MI, are elucidated, and a
      means of presenting the results in the form of a multi-situational EOL strategy
      graph is described. The impact of the European Union Directive regarding Waste
      Electric and Electronic Equipment (WEEE) on EOL trade-offs between energy
      recovery and cost was also considered for both locations.

PMID- 14700315
TI  - Sustainability science and engineering: the emergence of a new metadiscipline.
AB  - A case is made for growth of a new metadiscipline of sustainability science and
      engineering. This new field integrates industrial, social, and environmental
      processes in a global context. The skills required for this higher level
      discipline represent a metadisciplinary endeavor, combining information and
      insights across multiple disciplines and perspectives with the common goal of
      achieving a desired balance among economic, environmental, and societal
      objectives. Skills and capabilities that are required to support the new
      metadiscipline are summarized. Examples of integrative projects are discussed in
      the areas of sustainability metrics and integration of industrial, societal, and
      environmental impacts. It is clear that a focus on green engineering that employs
      pollution prevention and industrial ecology alone are not sufficient to achieve
      sustainability, because even systems with efficient material and energy use can
      overwhelm the carrying capacity of a region or lead to other socially
      unacceptable outcomes. To meet the educational and human resource needs required
      for this new discipline, the technological and environmental awareness of society
      must be elevated and a sufficient and diverse pool of human talent must be
      attracted to this discipline.

PMID- 14700316
TI  - Green chemical engineering aspects of reactive distillation.
AB  - Reactive or catalytic distillation technology combines chemical synthesis steps
      with separations by distillation. This combination can lead to intensified, high
      efficiency process systems with significant green engineering attributes. New
      applications and understanding have prompted growth in the use of reactive
      distillation for a variety of chemical syntheses, especially esterifications and
      etherifications involving oxygenated hydrocarbons. We describe several
      applications and the potential and tradeoffs for reactive distillation technology
      in the context of green engineering principles.

PMID- 14700317
TI  - Designing resilient, sustainable systems.
AB  - Pursuit of sustainable development requires a systems approach to the design of
      industrial product and service systems. Although many business enterprises have
      adopted sustainability goals, the actual development of sustainable systems
      remains challenging because of the broad range of economic, environmental and
      social factors that need to be considered across the system life cycle.
      Traditional systems engineering practices try to anticipate and resist
      disruptions but may be vulnerable to unforeseen factors. An alternative is to
      design systems with inherent "resilience" bytaking advantage of fundamental
      properties such as diversity, efficiency, adaptability, and cohesion. Previous
      work on sustainable design has focused largely upon ecological efficiency
      improvements. For example, companies have found that reducing material and energy
      intensity and converting wastes into valuable secondary products creates value
      for shareholders as well as for society at large. To encourage broader systems
      thinking, a design protocol is presented that involves the following steps:
      identifying system function and boundaries, establishing requirements, selecting
      appropriate technologies, developing a system design, evaluating anticipated
      performance, and devising a practical means for system deployment. The approach
      encourages explicit consideration of resilience in both engineered systems and
      the larger systems in which they are embedded.

PMID- 14700318
TI  - Industrial applications using BASF eco-efficiency analysis: perspectives on green
      engineering principles.
AB  - Life without chemicals would be inconceivable, but the potential risks and
      impacts to the environment associated with chemical production and chemical
      products are viewed critically. Eco-efficiency analysis considers the economic
      and life cycle environmental effects of a product or process, giving these equal
      weighting. The major elements of the environmental assessment include primary
      energy use, raw materials utilization, emissions to all media, toxicity, safety
      risk, and land use. The relevance of each environmental category and also for the
      economic versus the environmental impacts is evaluated using national emissions
      and economic data. The eco-efficiency analysis method of BASF is briefly
      presented, and results from three applications to chemical processes and products
      are summarized. Through these applications, the eco-efficiency analyses mostly
      confirm the 12 Principles listed in Anastas and Zimmerman (Environ. Sci. Technol.
      2003, 37(5), 94A), with the exception that, in one application, production
      systems based on bio-based feedstocks were not the most eco-efficient as compared
      to those based on fossil resources. Over 180 eco-efficiency analyses have been
      conducted at BASF, and their results have been used to support strategic decision
      making, marketing, research and development, and communication with external
      parties. Eco-efficiency analysis, as one important strategy and success factor in
      sustainable development, will continue to be a very strong operational tool at
      BASF.

PMID- 14700319
TI  - Promoting green engineering through green chemistry.
AB  - The decisions made by chemists in designing chemical products and processes
      directly impactthe options available to engineers. The physical and chemical
      properties of a material, for example, dictate the type of reactor that must be
      used in a given process. The task of the engineer is simplified when chemists
      design products and processes that reduce or eliminate the use and generation of
      hazardous substances. Green chemistry provides a foundation on which to build
      green engineering. This paper highlights green chemistry technologies that
      minimize the need for engineering safeguards in the areas of feedstocks,
      reagents, solvents, and syntheses.

PMID- 14700320
TI  - Disassembly factories for electrical and electronic products to recover resources
      in product and material cycles.
AB  - Cycle economy as a paradigm for industry in the 21st century depends on the
      economical and ecological treatment of limited resources. The objective is to
      achieve more use with fewer resources to increase the use-productivity of these
      resources. The European Union, aware of the adverse environmental impacts
      associated with electrical and electronic consumer goods in particular, has
      passed legislation regulating their appropriate end-of-life treatment. Adaptation
      processes, including essential disassembly and re-assembly operations, contribute
      significantly toward the economical fulfillment of these new legal requirements.
      Typically, the disassembly of used products is characterized by a high rate of
      manual operations, wide variety of product types, and unknown product properties.
      To cope with such demands, life cycle units or product accompanying information
      systems, are being developed and used for acquiring data about a specific product
      throughout its life cycle to aid in determining the level of product
      deterioration. Modular disassembly processes and tools have been developed and
      realized to enable the handling of multiple productvariants. They are being
      implemented in prototypical hybrid disassembly systemsfor large- and small-size
      electrical and electronic consumer goods.

PMID- 14700321
TI  - Road map and principles for built environment sustainability.
AB  - The built environment, defined by the facilities and civil infrastructure systems
      that people use, is the fundamental foundation upon which a society exists,
      develops, and survives. As the main provider and the life cycle custodian of the
      built environment, the Architecture, Engineering, and Construction (AEC) industry
      plays a critical role in determining the quality, integrity, and longevity of
      this foundation. In the execution of these two roles, provider and custodian, the
      AEC industry has had a major direct and indirect impact on the natural
      environment, contributing both directly and indirectly to natural resource
      depletion and degradation, waste generation and accumulation, and environmental
      impact and degradation. These impacts are not unique to the AEC industry. Other
      industries face similar challenges, and for many years, a wide range of
      constituencies within them have been attempting the implementation of the concept
      of sustainability within what these industries do, how they do it, and with what
      as a possible mechanism to slow, reduce, eliminate these impacts, and even
      restore conditions to a better state. In the pursuit of sustainability, the AEC
      industry faces challenges posed by the unique attributes and characteristics
      nature of facilities and civil infrastructure systems, the complexities of the
      current processes for their delivery and use, and the diverse set of resources
      required for both their delivery and their use. This paper offers a road map and
      an initial set of principles to implement built environment sustainability as a
      starting point for an ongoing, industry-wide dialogue and debate.

PMID- 14700322
TI  - Development of parametric material, energy, and emission inventories for wafer
      fabrication in the semiconductor industry.
AB  - Currently available data suggest that most of the energy and material consumption
      related to the production of an integrated circuit is due to the wafer
      fabrication process. The complexity of wafer manufacturing, requiring hundreds of
      steps that vary from product to product and from facility to facility and which
      change every few years, has discouraged the development of material, energy, and
      emission inventory modules for the purpose of insertion into life cycle
      assessments. To address this difficulty, a flexible, process-based system for
      estimating material requirements, energy requirements, and emissions in wafer
      fabrication has been developed. The method accounts for mass and energy use atthe
      unit operation level. Parametric unit operation modules have been developed that
      can be used to predict changes in inventory as the result of changes in product
      design, equipment selection, or process flow. A case study of the application of
      the modules is given for energy consumption, but a similar methodology can be
      used for materials, individually or aggregated.

PMID- 14700323
TI  - Research issues in sustainable consumption: toward an analytical framework for
      materials and the environment.
AB  - We define key research questions as a stimulus to research in the area of
      industrial ecology. The first group of questions addresses analytical support for
      green engineering and environmental policy. They relate to (i) tools for green
      engineering, (ii) improvements in life cycle assessment, (iii) aggregation of
      environmental impacts, and (iv) effectiveness of a range of innovative policy
      approaches. The second group of questions addresses the dynamics of technology,
      economics, and environmental impacts. They relate to (v) the environmental
      impacts of material and energy consumption, (vi) the potential for material
      efficiency, (vii) the relation of technological and economic development to
      changes in consumption patterns, and (viii) the potential for technology to
      overcome environmental impacts and constraints. Altogether, the questions create
      an intellectual agenda for industrial ecology and integrate the technological and
      social aspects of sustainability.

PMID- 14700324
TI  - Constrained optimization for green engineering decision-making.
AB  - Green engineering requires the designer to consider a very extensive set of
      environmental impacts. To minimize these impacts, the designer must significantly
      expand his or her "toolset" of product design concepts, alternative materials,
      manufacturing systems, and analytic methods for addressing life cycle impacts.
      This can overwhelm a designer, who then resorts to overly simplistic rules or
      checklists out of necessity. The central issue is how to identify all "pollution
      prevention pays" opportunities and then how to deal with the unavoidable
      tradeoffs that arise after all these opportunities have been exhausted. This
      paper presents a framework for employing mathematical decision modeling toward
      this end. A domain-independent constrained optimization formulation is presented.
      A multiattribute utility function reflects the willingness to pay for
      environmental improvement and is the basis of the objective function. The
      feasibility constraints reflect the unavoidable tradeoffs. Several case studies
      are presented, including power systems, floor tile manufacturing, and computer
      systems.

PMID- 14700325
TI  - Development of service-oriented products based on the inverse manufacturing
      concept.
AB  - To achieve sustainability, resource consumption and waste generation must be
      drastically decreased. For societal acceptance, preservation of both quality of
      life and corporate profits are essential. One promising approach is to shift the
      source of value from the amount of product sold to the quality of services the
      product provides. This paper describes the need for redesigning recycling systems
      from a manufacturing perspective and then discusses the possibility of this
      "servicification" of products, describing our experience with prototype
      development. We discuss development of product prototypes and their business,
      using consumer facsimile machines as an example of "service-oriented products".
      Traditional thought presumes that only products comprising new materials and
      components are valuable. Consideration of a service-oriented product can serve as
      a stimulus to revise this mode of thought and to control delivery and quality of
      disposed products. This paper also provides a life cycle simulation of the
      developed service-oriented business. Simulation results indicate that service
      oriented business can potentially reduce environmental impact while extending
      business opportunities from the viewpoint of whole product life cycles.

PMID- 14700326
TI  - Life cycle optimization of automobile replacement: model and application.
AB  - Although recent progress in automotive technology has reduced exhaust emissions
      per mile for new cars, the continuing use of inefficient, higher-polluting old
      cars as well as increasing vehicle miles driven are undermining the benefits of
      this progress. As a way to address the "inefficient old vehicle" contribution to
      this problem, a novel life cycle optimization (LCO) model is introduced and
      applied to the automobile replacement policy question. The LCO model determines
      optimal vehicle lifetimes, accounting for technology improvements of new models
      while considering deteriorating efficiencies of existing models. Life cycle
      inventories for different vehicle models that represent materials production,
      manufacturing, use, maintenance, and end-of-life environmental burdens are
      required as inputs to the LCO model. As a demonstration, the LCO model was
      applied to mid-sized passenger car models between 1985 and 2020. An optimization
      was conducted to minimize cumulative carbon monoxide (CO), non-methane
      hydrocarbon (NMHC), oxides of nitrogen (NOx), carbon dioxide (CO2), and energy
      use over the time horizon (1985-2020). For CO, NMHC, and NOx pollutants with
      12000 mi of annual mileage, automobile lifetimes ranging from 3 to 6 yr are
      optimal for the 1980s and early 1990s model years while the optimal lifetimes are
      expected to be 7-14 yr for model year 2000s and beyond. On the other hand, a
      lifetime of 18 yr minimizes cumulative energy and CO2 based on driving 12000
      miles annually. Optimal lifetimes are inversely correlated to annual vehicle
      mileage, especially for CO, NMHC, and NOx emissions. On the basis of the
      optimization results, policies improving durability of emission controls,
      retiring high-emitting vehicles, and improving fuel economies are discussed.

PMID- 14700327
TI  - Global sustainability and key needs in future automotive design.
AB  - The number of light vehicle registrations is forecast to increase worldwide by a
      factor of 3-5 over the next 50 years. This will dramatically increase
      environmental impacts worldwide of automobiles and light trucks. If light
      vehicles are to be environmentally sustainable globally, the automotive industry
      must implement fundamental changes in future automotive design. Important factors
      in assessing automobile design needs include fuel economy and reduced emissions.
      Many design parameters can impact vehicle air emissions and energy consumption
      including alternative fuel or engine technologies, rolling resistance,
      aerodynamics, drive train design, friction, and vehicle weight. Of these, vehicle
      weight is key and will translate into reduced energy demand across all energy
      distribution elements. A new class of vehicles is needed that combines ultra
      light design with a likely hybrid or fuel cell engine technology. This could
      increase efficiency by a factor of 3-5 and reduce air emissions as well. Advanced
      lightweight materials, such as plastics or composites, will need to overtake the
      present metal-based infrastructure. Incorporating design features to facilitate
      end-of-life recycling and recovery is also important. The trend will be towards
      fewer materials and parts in vehicle design, combined with ease of disassembly.
      Mono-material construction can create vehicle design with improved recyclability
      as well as reduced numbers of parts and weight.

PMID- 14700328
TI  - A symbolic methodology to improve disassembly process design.
AB  - Millions of end-of-life electronic components are retired annually due to the
      proliferation of new models and their rapid obsolescence. The recovery of
      resources such as plastics from these goods requires their disassembly. The time
      required for each disassembly and its associated cost is defined by the
      operator's familiarity with the product design and its complexity. Since model
      proliferation serves to complicate an operator's learning curve, it is worthwhile
      to investigate the benefits to be gained in a disassembly operator's preplanning
      process. Effective disassembly process design demands the application of green
      engineering principles, such as those developed by Anastas and Zimmerman
      (Environ. Sci. Technol. 2003, 37, 94A-101A), which include regard for product
      complexity, structural commonality, separation energy, material value, and waste
      prevention. This paper introduces the concept of design symbolsto help the
      operator more efficiently survey product complexity with respect to location and
      number of fasteners to remove a structure that is common to all electronics: the
      housing. With a sample of 71 different computers, printers, and monitors, we
      demonstrate that appropriate symbols reduce the total disassembly planning time
      by 13.2 min. Such an improvement could well make efficient the separation of
      plastic that would otherwise be destined for waste-to-energy or landfill. The
      symbolic methodology presented may also improve Design for Recycling and Design
      for Maintenance and Support.

PMID- 14700329
TI  - Hydroformylation of 1-hexene in supercritical carbon dioxide: characterization,
      activity, and regioselectivity studies.
AB  - The hydroformylation of alkenes is a major commercial process used for the
      production of oxygenated organic compounds. When the hydroformylation reaction is
      performed using a homogeneous catalyst, an organic or aqueous solvent is
      employed, and a significant effort must be expended to recover the catalyst so it
      can be recycled. Development of a selective heterogeneous catalyst would allow
      simplification of the process design in an integrated system that minimizes waste
      generation. Recent studies have shown that supercritical carbon dioxide (scCO2)
      as a reaction solvent offers optimal environmental performance and presents
      advantages for ease of product separation. In particular, we have considered the
      conversion of 1-hexene to heptanal using rhodium- and platinum-phosphine
      catalysts tethered to supports insoluble in scCO2 to demonstrate the advantages
      and to understand the limitations of a solid-catalyzed process. One of the
      historical limitations of supported catalysts is the inability to control product
      regioselectivity. To address this concern, we have developed tethered catalysts
      with phosphinated silica and controlled pore size MCM-41 and MCM-20 supports that
      provide improved regioselectivity and conversion relative to their nonporous
      equivalents. Platinum catalysts supported on MCM-type supports were the most
      regioselective whereas the analogous rhodium catalysts were the most active for
      hydroformylation of 1-hexene in scCO2.

PMID- 14700330
TI  - Greener by design.
AB  - Process simulation models and other design tools allow engineers to design,
      simulate, and optimize chemical processes. However, there is a critical need to
      incorporate green engineering into the design of these processes. This calls for
      extending the breadth of the design process. This paper presents an integrated
      framework for greener design. The framework starts the decision-making as early
      as the chemical and material selection stage and also includes management and
      planning decisions. The design goal is not restricted to profitability, but
      environmental and ecological objectives are also added. However, this integration
      poses challenging problem of discrete and continuous decisions, nonlinear models,
      and uncertainties. Furthermore, there are multiple and conflicting objectives to
      be considered. Therefore, the core of this integrated framework is the efficient
      algorithmic framework for multiobjective optimization under uncertainty. Two real
      world case studies are presented that illustrate the promise of such a framework.

PMID- 14700331
TI  - Life cycle assessment of automobile/fuel options.
AB  - We examine the possibilities for a "greener" car that would use less material and
      fuel, be less polluting, and would have a well-managed end-of-life. Light-duty
      vehicles are fundamental to our economy and will continue to be for the
      indefinite future. Any redesign to make these vehicles greener requires consumer
      acceptance. Consumer desires for large, powerful vehicles have been the major
      stumbling block in achieving a "green car". The other major barrier is inherent
      contradictions among social goals such as fuel economy, safety, low emissions of
      pollutants, and low emissions of greenhouse gases, which has led to conflicting
      regulations such as emissions regulations blocking sales of direct injection
      diesels in California, which would save fuel. In evaluating fuel/vehicle options
      with the potential to improve the greenness of cars [diesel (direct injection)
      and ethanol in internal combustion engines, battery-powered, gasoline hybrid
      electric, and hydrogen fuel cells], we find no option dominates the others on all
      dimensions. The principles of green design developed by Anastas and Zimmerman
      (Environ. Sci. Technol. 2003, 37, 94A-101A) and the use of a life cycle approach
      provide insights on the key sustainability issues associated with the various
      options.

PMID- 14700332
TI  - Green engineering education through a U.S. EPA/academia collaboration.
AB  - The need to use resources efficiently and reduce environmental impacts of
      industrial products and processes is becoming increasingly important in
      engineering design; therefore, green engineering principles are gaining
      prominence within engineering education. This paper describes a general framework
      for incorporating green engineering design principles into engineering curricula,
      with specific examples for chemical engineering. The framework for teaching green
      engineering discussed in this paper mirrors the 12 Principles of Green
      Engineering proposed by Anastas and Zimmerman (Environ. Sci. Technol. 2003, 37,
      94A-101A), especially in methods for estimating the hazardous nature of
      chemicals, strategies for pollution prevention, and approaches leading to
      efficient energy and material utilization. The key elements in green engineering
      education, which enlarge the "box" for engineering design, are environmental
      literacy, environmentally conscious design, and beyond-the-plant boundary
      considerations.

PMID- 14700333
TI  - Plastics disassembly versus bulk recycling: engineering design for end-of-life
      electronics resource recovery.
AB  - Annual plastic flows through the business and consumer electronics manufacturing
      supply chain include nearly 3 billion lb of high-value engineering plastics
      derived from petroleum. The recovery of resource value from this stream presents
      critical challenges in areas of materials identification and recycling process
      design that demand new green engineering technologies applied together with life
      cycle assessment and ecological supply chain analysis to create viable plastics
      to-plastics supply cycles. The sustainable recovery of potentially high-value
      engineering plastics streams requires that recyclers either avoid mixing plastic
      parts or purify later by separating smaller plastic pieces created in volume
      reduction (shredding) steps. Identification and separation constitute significant
      barriers in the plastics-to-plastics recycling value proposition. In the present
      work, we develop a model that accepts randomly arriving electronic products to
      study scenarios by which a recycler might identify and separate high-value
      engineering plastics as well as metals. Using discrete eventsimulation,we compare
      current mixed plastics recovery with spectrochemical plastic resin identification
      and subsequent sorting. Our results show that limited disassembly with whole-part
      identification can produce substantial yields in separated streams of recovered
      engineering thermoplastics. We find that disassembly with identification does not
      constitute a bottleneck, but rather, with relatively few workers, can be
      configured to pull the process and thus decrease maximum staging space
      requirements.

PMID- 14700334
TI  - Demineralization demons.

PMID- 14700335
TI  - The marginal seal of a flowable composite, an injectable resin modified glass
      ionomer and a compomer in primary molars--an in vitro study.
AB  - The present study was carried out to compare the marginal microleakage of some
      newer materials viz. a flowable composite, an injectable resin modified glass
      ionomer and a compomer in Class I cavities of 30 non carious primary molars.
      After 0.5% basic fuchsin dye penetration and sectioning, the teeth were studied
      under stereomicroscope. The results obtained revealed that flowable composite
      showed significantly lower microleakage (p<0.05) as compared to injectable resin
      modified glass ionomer and compomer. However, no significant difference was
      observed when injectable resin modified glass-ionomer cement was compared to
      compomer. This concludes that flowable composite materials adhere better to the
      primary teeth than resin modified glass ionomer and compomer.

PMID- 14700336
TI  - Congenital muscular dystrophy--a case report.
AB  - A rare case of congenital muscular dystrophy with unique oro-facial
      manifestations is presented. Dental considerations and successful management
      techniques are discussed.

PMID- 14700337
TI  - Comparison of the effect of topical fluorides on the commercially available
      conventional glass ionomers, resin modified glass ionomers and polyacid modified
      composite resins--an in vitro study.
AB  - This study was undertaken to assess the effect of a single application of three
      professionally applied topical fluoride agents (Sodium fluoride 2%, Stannous
      fluoride 8% and APF 1.23%) on the surfaces of six modern esthetic restorative
      materials used in pediatric dentistry viz., two conventional glass ionomers (Fuji
      II and Shofu-restorative), two resin modified glass ionomers (Vitremer, with and
      without glaze, and Photac-fil Quick) and two Polyacid modified composite resins
      (Luxat and Hytac Aplitip). Mean surface roughness and surface micro hardness
      (SMH) measurements were the parameters employed for comparison. Results showed
      that APF gel applications significantly increased the surface roughness
      measurements and decreased SMH of all tested materials, which was pronounced in
      conventional glass ionomers when compared with resin modified glass ionomers and
      polyacid modified composite resins. NaF and SnF2 produced a statistically
      significant increase in the surface roughness of conventional glass ionomers
      without any significant change in surface roughness and SMH on rest of the
      materials tested, except for NaF on SMH values of Fuji II, which was
      statistically significant.

PMID- 14700338
TI  - Implementation of behaviour management techniques--how well accepted they are
      today.
AB  - Dynamic changes in society with working parents and smaller nuclear families have
      brought about a sea of changes in parental attitudes and anxieties towards their
      children. This has affected the perception and implementation of behaviour
      modification techniques by the dentist. Today, the significance of Tell Show Do
      technique and its efficiency in behaviour modification is questionable.
      Insistence of parents on conscious sedation is seen to be on the rise. This study
      aimed to assess the change in the utilization pattern of behaviour management
      techniques by pediatric dentists of Punjab in the past five years along with
      identification of change in parental attitude towards these techniques.

PMID- 14700339
TI  - EEC syndrome--a case report.
AB  - EEC syndrome is a multiple congenital anomaly syndrome characterized by
      ectodermal dysplasia, distal limb anomaly, cleft lip and palate and ocular
      adnexia anomalies. A case report of a 10 year old female patient with EEC is
      presented and it is emphasised that management of these cases requires a
      multidisciplinary approach. Early diagnosis will allow parents to get accurate
      counseling and in particular obtain reassurance regarding the low risk of mental
      handicap.

PMID- 14700340
TI  - Etching with EDTA--an in vitro study.
AB  - In the present study, 25% EDTA, in gel form, was used to analyse its
      micromorphological effects on tooth surfaces with the objective to see the
      effectiveness of EDTA in etching so as to replace phosphoric acid as an etchant.
      EDTA has neutral pH (6.4 - 7.4) and is known to open & widen the dentinal tubules
      as well as remove the smear layer. An in vitro study was conducted on
      orthodontically extracted premolars with 25% EDTA as an etchant which was applied
      on prepared tooth surfaces for 15 seconds, 1 minute and 3 minutes. The effects of
      EDTA gel was observed under SEM and results tabulated and evaluated. There was
      statistically significant differences between the 3 etching time groups and the
      results indicate that etching with 25% EDTA for 15 seconds is inadequate. The
      best results were obtained in the 3 minute time etch group. The results so
      obtained can be attributed to the fact that EDTA acts selectively and/or requires
      more time for action.

PMID- 14700341
TI  - Familial occurence of mesiodens--a case report.
AB  - Molariform supernumerary teeth in the maxillary central incisor area are
      uncommon. This article reports the presence of a molariform mesiodens in daughter
      and a conical mesiodens in father. Detailed investigation into family history of
      patients with mesiodens is needed. Though the etiology of this dental anomaly
      remains unclear, genetics as a key factor in the development of supernumerary
      teeth is highlighted.

PMID- 14700342
TI  - West Nile virus: the Indian scenario.
AB  - West Nile virus (WNV) is an important arthropod borne flavivirus; usually causes
      a mild infection called West Nile fever (WNF) in human and horses. Mosquitoes are
      the principal vectors of WNV. Various Culex species are found to act as vectors
      in different geographical regions. The virus is maintained in a bird-mosquito
      cycle in nature. In India, Culex mosquitoes are tentatively incriminated as
      vectors of WNV. Experimental studies have shown that Culex tritaeniorhynchus, Cx.
      vishnui, Cx. bitaeniorhynchus and Cx. univittatus, Culex pipiens fatigans and
      Aedes albopictus could act as potential vectors of WNV. Transovarial transmission
      of WNV has been experimentally demonstrated in Culex mosquitoes. Apart from
      mosquitoes, the role of other arthropods is also considered in the maintenance of
      WNV during inter-enzootic periods. The possible role of ardeid birds in the
      maintenance of WNV has been described in India. Though very few clinically overt
      cases of human encephalitis due to WNV are observed, Japanese encephalitis virus
      (JEV) is found to dominate in southern India. WNF in horses has not been
      documented in India. JEV immunized monkeys were protected from WNV challenge and
      the WNV immunization was found to reduce the disease severity due to JEV. Based
      on the limited genome sequence analysis, the Indian isolates are grouped together
      under the genetic lineage-I. WNV infection is diagnosed by IgM antibody capture
      enzyme linked immunosorbant assay, haemagglutination inhibition test,
      neutralization test and reverse transcriptase-polymerase chain reaction (RT-PCR).
      For the effective control of Culex mosquitoes, integrated vector control
      strategies are recommended. Specific methods are not available for the treatment
      of WNV infection. However, in patients with encephalitis supportive therapy is
      recommended. Though a few candidate vaccines are under laboratory trial, no
      vaccine has been available commercially for the control of WNV infection in human
      and animals. In view of the global interest on WNV, this paper describes the
      present status of WNV in India.

PMID- 14700343
TI  - Bioavailability of rifampicin following concomitant administration of ethambutol
      or isoniazid or pyrazinamide or a combination of the three drugs.
AB  - BACKGROUND & OBJECTIVES: Poor bioavailability of rifampicin (R) in combination
      with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and
      ethambutol (E) is a subject of much concern for the last few decades. This could
      be due to an interaction between R and other drugs. An investigation was
      therefore undertaken to examine the bioavailability of R in the presence of H, Z
      and E or a combination of the three drugs. METHODS: The study included eight
      healthy volunteers, each being investigated on four occasions at weekly intervals
      once with R alone and with three of the four combinations on the three remaining
      occasions. A partially balanced incomplete block design was employed and the
      allocation of R or the drug combinations was random. Plasma concentrations of R
      at intervals up to 12 h were determined by microbiological assay using
      Staphylococcus aureus as the test organism. The proportion (%) dose of R as R
      plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also
      determined. Bioavailability was expressed as an index (BI) of area under time
      concentration curve (AUC) calculated from the plasma concentrations or proportion
      of dose of R excreted as R plus DR in urine with the combinations to that with R
      alone. RESULTS: The bioavailability indices based on AUC were 0.96 with RE, 0.76
      with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations
      (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A
      second investigation revealed that the decrease of bioavailability of R with H
      was not due to the excipients present in H tablets. INTERPRETATION & CONCLUSION:
      Isoniazid alone or in combination with E and Z reduces the bioavailability of R.
      Urinary excretion data offer a simple and non invasive method for the assessment
      of bioavailability of R.

PMID- 14700344
TI  - Expression & immunogenicity of malaria merozoite peptides displayed on the small
      coat protein of chimaeric cowpea mosaic virus.
AB  - BACKGROUND & OBJECTIVES: Foreign peptide sequences can be inserted into the betaB
      betaC loop of the cowpea mosaic virus (CPMV) small coat protein (SCP) to yield
      functional chimaeric viruses. Immunisation with chimaeric CPMV elicits immune
      responses that protect against human immunodeficiency and mink enteritis viruses.
      The present study was undertaken to investigate the expression of a B cell
      epitope from the merozoite surface antigen-1 of the malaria parasite Plasmodium
      falciparum (PfMSP1) in CPMV for an epitope based vaccine. METHODS: DNA encoding a
      19 aa sequence (VTHESYQEL VKKLEALEDA, termed P109), the N-terminus of the mature
      PfMSP1, was cloned into SCP gene yielding a chimaeric virus CPMV-P109. CPMV-P109
      was propagated in cowpea plants. The immunogenicity of purified recombinant virus
      in rabbits was investigated. RESULTS: CPMV-P109 developed a systemically
      spreading infection in cowpea, with normal viral morphology. The P109 epitope was
      detected on CPMV-P109 by ELISA with an antiserum produced against homopolymeric
      P109. Immunisation of rabbits with CPMV-P109 yielded antibodies that, although
      were predominantly directed against virus-specific epitopes, also recognized the
      P109 peptide on the recombinant virus and free P109 peptide. These antibodies
      however, did not react with the native antigen on merozoite by
      immunofluorescence. INTERPRETATION & CONCLUSION: The results indicate that
      selecting immunodominant peptide epitopes and presenting them in a near native
      conformation are important for generating biologically relevant antibodies in the
      CPMV expression system. Further, the findings draw attention to the importance of
      measuring immune responses to the viral vector antigens, a preponderance of which
      can result in undesirable effects such as autoimmunity and hypersensitivity in
      immunized hosts.

PMID- 14700345
TI  - Haemolysin test for characterization of immune ABO antibodies.
AB  - BACKGROUND & OBJECTIVES: Antibodies with haemolytic properties are common within
      the ABO system. These lytic antibodies are immunoglobulin G (IgG) and in high
      titres cause haemolysis during blood transfusion. Information on Immunoglobulin
      types and concentration of ABO haemolysins in Indian population is lacking. The
      present study was undertaken to know the usefulness of haemolysin test for
      characterization of immunoglobulin class of ABO antibodies. METHODS: Serum
      samples from 187 O group blood donors were screened for A and B haemolysins.
      Thirty five samples were treated with dithiothretiol (DTT) for characterization
      of Ig class. Antibody titre was compared with grade of haemolysis. RESULTS: Of
      the 51 strongly haemolytic serum samples, 32 (62.8%) had IgG titres of > or = 64
      after treatment with DTT. There was significant association (P<0.05) between
      grade of haemolysin and anti B IgG titre. INTERPRETATION & CONCLUSION: Haemolysin
      test was found to be a useful screening test to identify group O donors with high
      levels of IgG anti A and/or anti B for blood transfusion purposes.

PMID- 14700346
TI  - Urinary levels of nicotine & cotinine in tobacco users.
AB  - BACKGROUND & OBJECTIVES: Of the various biochemical markers used to validate the
      smoking status of a person, nicotine and continine are considered as good markers
      for both active and passive smoking. In the present study an attempt was made to
      estimate urinary levels of nicotine and cotinine in healthy individuals from
      north India using different types of tobacco to identify and validate the smoking
      status. METHODS: Twenty four hour urine sample of 130 healthy volunteers
      (smokers=70, passive smokers=20, tobacco chewers=20, non smokers=20) were
      analyzed by high-pressure liquid chromatography (HPLC) assay. Smokers were
      divided into different groups, viz., cigarette, bidi and hooka smokers. RESULTS:
      The mean values of nicotine (ng/ml) and cotinine (ng/ml) in urine were highest in
      cigarette smokers (nicotine=703.50+/-304.34; cotinine=2736.20+/-983.29), followed
      by hooka smokers (nicotine 548.0+/-103.47 and cotinine 2379.0+/-424.25), and bidi
      smokers (nicotine=268.53+/-97.62, cotinine=562.60+/-249.38). There was no
      correlation of nicotine or cotinine values with smoking index. In passive smokers
      (nicotine=109.75+/-22.33, cotinine=280.75+/-86.30) and in nonsmokers, the values
      were much lower (nicotine=55.00+/-13.71, cotinine=7.30+/-2.47) compared to
      smokers. In tobacco chewers, the values for nicotine and cotinine were 447.75+/
      145.09 and 2178.30+/-334.29 respectively. INTERPRETATION & CONCLUSION: All forms
      of tobacco users had significantly higher values compared to passive smokers and
      nonusers. Thus, cotinine and nicotine levels in urine may be considered as good
      indicators to assess the exposure to tobacco in our population.

PMID- 14700347
TI  - Lipoic acid restores antioxidant system in tissues of hyperinsulinaemic rats.
AB  - BACKGROUND & OBJECTIVES: Feeding rats with high fructose induces insulin
      resistance, hyperinsulinaemia, elevation of blood glucose level and impaired
      glucose tolerance. Oxidative stress plays a vital role in pathology associated
      with insulin resistance. The present study was to investigate the effects of
      alpha-lipoic acid (LA) on the oxidant-antioxidant balance in liver and kidney of
      high fructose-fed rats. METHODS: Male Wistar rats (170-180 g) were divided into
      six groups. The control group received diet containing starch; the fructose group
      was given a high fructose diet (>60% of total calories); the third and fourth
      groups were given fructose diet and administered with two different doses of
      lipoic acid as low dose (35 mg/kg body weight) and high dose (70 mg/kg bw)
      intraperitoneally using olive oil as vehicle; the fifth group received control
      diet and was administered with lipoic acid (70 mg/kg bw); the sixth group
      received the control diet and olive oil. The rats were maintained in their
      respective dietary regimen for 20 days. Lipid peroxidation indices and
      antioxidant status in liver and kidney were quantitated. RESULTS: The rats fed
      fructose showed increased levels of lipid hydroperoxides, thiobarbituric acid
      reactive substances (TBARS), conjugated dienes, and impaired antioxidant defence
      potential as evidenced by a decrease in the levels of non-enzymatic and enzymatic
      antioxidants. Treatment with LA to the fructose-fed rats mitigated these
      alterations and LA was effective uniformly at both the closes. Increased lipid
      peroxidation and inadequate antioxidant system are observed in the high dose
      fructose-fed rats. INTERPRETATION & CONCLUSION: LA administration restored the
      antioxidant potential and lowered lipid peroxidation. These findings strengthen
      the utility of LA in the management of insulin resistance and associated
      pathology.

PMID- 14700348
TI  - Seroprevalence of human immunodeficiency virus (HIV) infection among tuberculosis
      patients in Tamil Nadu.
AB  - BACKGROUND & OBJECTIVES: The dual epidemic of HIV and tuberculosis is a cause for
      concern in those countries where these two infections are prevalent in epidemic
      proportions. We undertook a survey at two sites in North Arcot district of Tamil
      Nadu in 1992-1993, to know the seroprevalence of HIV infection among tuberculosis
      patients. The objective of this study was to re-examine the prevalence of HIV
      infection among tuberculosis patients in a repeat survey. METHODS: The study was
      undertaken in four centres: District Tuberculosis Centre (DTC), Vellore,
      Tuberculosis Sanatorium, Pennathur (Vellore), District TB Centre (DTC),
      Kancheepuram and the Government Thiruvotteswarar Tuberculosis Hospital (GTTH),
      Chennai in the northern part of Tamil Nadu during 1997-1998. A total of 2361
      newly diagnosed TB patients were registered in this study. HIV serology after pre
      test counseling was done along with sputum examination for acid-fast bacillus by
      smear and culture for mycobacteria for all patients. RESULTS: The overall HIV
      seroprevalence among TB patients was 4.7 per cent. The highest HIV seropositivity
      rate was found among patients aged 30-39 yr (10.6%). HIV seroprevalence showed a
      wide variation among the different centres ranging from 0.6. per cent in DTC,
      Kancheepuram to 9.4 per cent in Pennathur Sanatorium, Vellore. Sputum smear
      positivity was 88 per cent among the HIV-negative and 83 per cent among HIV
      positive tuberculosis patients. INTERPRETATION & CONCLUSION: HIV infection is on
      the rise among TB patients in Tamil Nadu. Acid-fast smear microscopy is adequate
      for the diagnosis of pulmonary tuberculosis, and drug resistance among HIV
      positive patients is not a major problem at this point of time; hence
      antituberculosis regimens recommended by the Revised National Tuberculosis
      Control Program (RNTCP) can be used to treat HIV positive patients with
      tuberculosis.

PMID- 14700349
TI  - Need for specific & routine strategy for the diagnosis of genital chlamydial
      infection among patients with sexually transmitted diseases in India.
AB  - BACKGROUND & OBJECTIVES: With increasing burden of human immunodeficiency virus
      (HIV) infection acquired immunodeficiency syndrome (AIDS) in India, documentation
      on the epidemiology of genital chlamydial infections in high-risk patients with
      sexually transmitted diseases (STD) is of significant public health value.
      Specific diagnosis is essential to prevent the morbidity due to the chlamydial
      infection and to reduce the risk of acquiring HIV infection. The present study
      was undertaken to analyse the usefulness of culture and antigen detection by
      direct fluorescent antibody (DFA) test for assessing the rate of Chlamydia
      trachomatis infection in symptomatic patients and feasibility of these tests for
      routine adoption in Indian setting. METHODS: Clinically diagnosed patients of
      both sex (n=143) attending the Institute of Sexually Transmitted Diseases,
      Government General Hospital, Chennai who consented for the study, were enrolled.
      Clinical and demographic details were recorded on a stratified proforma. Genital
      swab specimens collected from them were subjected for culture using McCoy cell
      line and for antigen detection by DFA testing. RESULTS: C. trachomatis was
      isolated in 27 of the total 143 patients (18.9%). Culture positivity was seen in
      11 of the 63 (17.5%) males and in 16 of 80 (20%) females. DFA detected C.
      trachomatis specific antigen in 35 patients (24.5%); 15 (23.8%) males and 20
      (25%) females. The rate of C. trachomatis diagnosis increased to 25.2 per cent by
      adopting both the methods as against 18.9 per cent by culture only and 24.5 per
      cent by DFA only. No association of C. trachomatis infection with any predictable
      genitourinary symptom (s), was seen. INTERPRETATION & CONCLUSION: The findings
      show a high infection rate for C. trachomatis in symptomatic patients with STD.
      Clinical symptoms alone can be unreliable in specifically predicting infections
      with C. trachomatis. Specific diagnostic tests need to be recommended for routine
      inclusion in the STD diagnosis to facilitate risk reduction of HIV infection in
      STD patients.

PMID- 14700350
TI  - Efficacy of insect parasitoid Dirhinus himalayanus (Hymenoptera: Chalcididae) &
      insect growth regulator, triflumuron against house fly, Musca domestica (Diptera:
      Muscidae).
AB  - BACKGROUND & OBJECTIVES: In fly management programme chemicals are extensively
      used. Combined use of insect growth regulator (IGR) and parasitoids would yield a
      better reduction in fly density, as exposure of fly larvae to sub lethal dose of
      IGR enhances pupal duration and thereby increases the exposure time for
      parasitism. The objective of the present study was to explore the additive effect
      of both Dirhinus himalayanus, an insect parasitoid and triflumuron, an IGR in
      controlling house fly, Musca domestica. METHODS: In the field trial the study
      sites were allocated based on two-way ANOVA performed on one year pre-treatment
      survey. Parasitoid release and IGR treatment were initiated when the growth rate
      (lambda) of M. domestica was in an increasing trend. Parasitoids were released at
      a rate of 6 number/m2 for three months (February-April 2000), whereas IGR was
      applied at a dose of 10 mg/m2 at fortnightly interval from February to December
      2000. Control efficacy was assessed using Mulla's formula. RESULTS: Reduction in
      puparia density was 59.29, 48.67 and 69.08 per cent respectively in areas, where
      parasitoids, ICR and combination of both IGR and parasitoids were used.
      Corresponding figures for adult population were 55.69, 49.71 and 77.14 per cent
      respectively. The per cent reduction in puparia and adult density was
      significantly (P<0.05) higher in the experimental areas than in the check. When
      the per cent reduction in adult and puparia density among different experimental
      areas was compared, it was observed that the reduction in fly density was
      significantly higher in the areas, where the combination of both parasitoid-IGR
      (P=0.00102) and IGR (P=0.03175) were used, while in areas where parasitoid
      (P=0.06191) were released the reduction in fly density was not significant.
      Similarly, there was a significant reduction in puparia density in areas where
      both parasitoid-IGR combination (P=0.0001) or IGR (P=0.002) were used, whereas in
      parasitoid (P=0.0612) released areas it was not significant. INTERPRETATION &
      CONCLUSION: The results show that the combined use of parasitoid and IGR is
      effective in reducing puparia and fly density. Therefore, for sustenance of an
      effective fly control programme, both parasitoid and IGR may be used.

PMID- 14700351
TI  - Prevalence & etiology of nutritional anaemia among school children of urban
      slums.
AB  - BACKGROUND & OBJECTIVES: The prevalence of anaemia has been well studied
      particularly on etiology of nutritional anaemia in children of age group 5-10.9
      yr in India. The present study was carried out to find out the prevalence and
      etiology of nutritional anaemia among 5 to 10.9 yr old corporation school
      children from urban slums. METHODS: Urban Delhi slums were divided into four
      areas and one corporation school from each area was randomly selected. A total of
      406 children from 4 each school were randomly selected over a period of one yr
      and prevalence of anaemia was estimated. Another subset of 95 anaemic children
      admitted to the hospital during the same period were evaluated for the etiology
      of nutritional anaemia. RESULTS: Prevalence of anaemia as judged by WHO
      recommended cut-off values of haemoglobin among these children was 41.8 per cent.
      Pure or mixed iron deficiency anaemia was the commonest type of anaemia noted in
      68.42 per cent (65 of 95) children followed by pure or mixed B12 deficiency
      noticed in 28.42 per cent (27 of 95) anaemic children. Of the pure variety, iron
      deficiency was the commonest cause occurring in 41.05 per cent (39 of 95)
      children. INTERPRETATION & CONCLUSION: Childhood anaemia continues to be a
      significant public health problem in school children aged 5 to 10.9 yr and iron
      deficiency either alone or in combination is the commonest nutritional cause of
      anaemia. Pure or mixed vitamin B12 deficiency is an important but yet not
      commonly recognized cause of anaemia among these children.

PMID- 14700352
TI  - Effect of ischaemia & aglycaemia on the synaptic transmission in neonatal rat
      spinal cord in vitro.
AB  - BACKGROUND & OBJECTIVES: In vitro models of anoxia have revealed severe changes
      in neuronal functions after ischaemia but not after aglycaemia, although
      hypoglycaemia produced severe neuronal dysfunctions sometimes leading to coma.
      The present study was therefore undertaken to examine and compare the effects of
      aglycaemia with that of ischaemia on synaptic transmission in vitro. METHODS:
      Spinal cord from the neonatal rat was isolated, hemisected and placed in a
      chamber perfused with standard physiological solution. The stimulation of a
      dorsal root elicited monosynaptic (MSR) and polysynaptic (PSR) reflex potentials
      in the segmental ventral root. The effects of suprefusing glucose free medium
      (aglycaemia) and superfusing glucose free and O2 free medium (ischaemia) were
      examined on these reflexes. RESULTS: Superfusion of aglycaemic solution did not
      alter the magnitude of MSR or PSR in the first 15 min and subsequently there was
      a time-dependent depression of the reflexes (P < 0.05). The ischaemic solution
      depressed the reflexes in a time-dependent manner from the very beginning. The 50
      per cent depression of the reflexes occurred around 25 and 15 min, for aglycaemia
      and ischaemia, respectively. In the presence of Mg2+, the aglycaemia-induced
      depression of MSR was completely blocked but the ischaemic response was
      attenuated partially as the reflex was abolished by 80 min. INTERPRETATION &
      CONCLUSION: The results of the present study indicate that the aglycaemia and
      ischaemia depressed the synaptic transmission to the same extent though there
      were differences in their onset and progress. Aglycaemia involves N-methyl-D
      aspartate (NMDA) receptor-dependent (Mg2+ sensitive) mechanism, while ischaemia
      induced depression involves other mechanisms in addition to NMDA.

PMID- 14700353
TI  - Antioxidant status & lipid peroxidation in patients with rheumatoid arthritis.
AB  - BACKGROUND & OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating, chronic
      multisystem disease with an unknown etiology. Recent findings indicate that
      increased oxidative stress and/or defective antioxidant status contribute to the
      etiology of RA. The present study was undertaken to examine the oxidant and
      antioxidant systems in patients with RA and healthy controls. METHODS: Twenty two
      patients with RA and 20 healthy volunteers were included in the study. Levels of
      malondialdehyde (MDA) and antioxidant vitamins (A, E, C) in serum samples were
      determined by high performance liquid chromatography (HPLC). Spectrophotometric
      methods were used to determine activity levels of antioxidant enzymes, superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px), in erythrocytes. RESULTS:
      MDA levels in patients with RA were found to be significantly (P<0.005) higher
      than controls whereas levels of vitamins A, E, C and activities of GSH-Px, SOD
      were lower in the patients compared to controls (P<0.005 for SOD and antioxidant
      vitamins; P<0.05 for GSH-Px). INTERPRETATION & CONCLUSION: There was an increased
      oxidative stress and a low antioxidant status in patients with RA. These changes
      are probably due to efforts for reducing lipid peroxidation and hence to lower
      tissue damage.

PMID- 14700354
TI  - Genetic and environmental mediation of the relationship between language and
      nonverbal impairment in 4-year-old twins.
AB  - This study of 4-year-old twins investigated the genetic and environmental origins
      of comorbidity between language impairment and nonverbal ability by testing the
      extent to which language impairment in one twin predicted nonverbal ability in
      the co-twin. Impairment of language ability was defined as scores below the 15th
      percentile on a general language scale derived from a battery of diverse language
      tests. Four hundred thirty-six children, members of 160 monozygotic (MZ) and 131
      same-sex dizygotic (DZ) twin pairs, were identified as language impaired.
      Language-impaired probands also suffered significant impairments in nonverbal
      ability. DeFries-Fulker extremes analysis showed evidence for substantial genetic
      mediation of the phenotypic relationship between language impairment and poor
      nonverbal ability in that language problems in one twin predicted poor nonverbal
      ability in the co-twin, much more so for MZ twins than for DZ twins. This finding
      held even when we excluded those children with language impairment whose
      nonverbal score indicated general cognitive delay. These results point to a
      general genetic factor that includes both language and nonverbal problems.

PMID- 14700355
TI  - The stability of primary language disorder: four years after kindergarten
      diagnosis.
AB  - The rates of change in the language status of children with language impairment
      unaccompanied by other developmental or sensory disorders (primary language
      disorder) were studied in a longitudinal sample of 196 children who were followed
      from kindergarten through 4th grade. Previous studies have shown that children
      with such language impairments have moderate rates of improvement during this age
      range. Also, those with the most specific deficits have the greatest likelihood
      of improvement. Cole and colleagues have hypothesized that such results could be
      due to the effect of regression to the mean (K. Cole, I. Schwartz, A. Notari, P.
      Dale, & P. Mills, 1995). This study used a baseline measure of language that was
      independent of the measure used for diagnosis in order to control for factors
      leading to regression to the mean. Patterns of change using the kindergarten
      diagnostic measure were compared to those using the baseline measure. Rates of
      diagnostic change between kindergarten and subsequent observation intervals
      showed patterns of change similar to those of past research. Comparisons using
      the baseline measure revealed no significant change in relative language status
      across the 4-year time period. The results showed that when the conditions for
      regression to the mean were controlled, the poor language of children with
      language impairments was very likely to persist during the primary school years.

PMID- 14700356
TI  - The acquisition of the English plural morpheme by native Mandarin Chinese
      speaking children.
AB  - Although the acquisition of the English plural morpheme by monolingual English
      speaking children (L1 learners) has been studied extensively, little is known
      about the processes through which native speakers of other languages (L2
      speakers) acquire the English plural morpheme. To understand the similarities and
      differences between L1 and L2 English plural morpheme acquisition, 10 native
      Mandarin-speaking children who immigrated to the United States between ages 5 and
      16 years were followed for 5 years. Their proficiency in English plural morpheme
      production was measured by a picture description task and by their spontaneous
      speech. In contrast to L1 learners who master the plural morpheme within 3 years
      of age, only 7 of these 10 L2 learners did so after 5 years of English exposure.
      Age of initial exposure to English and language environment explained individual
      differences to some extent. Participants' speech illustrated all error types made
      by L1 learners; however, L2 learners more frequently marked the same noun
      inconsistently in the same testing session, and more often overgeneralized the
      plural morpheme in singular or mass noun contexts. Differences between L2
      learners and L1 learners with specific language impairment are also discussed.

PMID- 14700357
TI  - Learning new words II: Phonotactic probability in verb learning.
AB  - Phonotactic probability, a measure of the likelihood of occurrence of a sound
      sequence, appears to facilitate noun learning (H. L. Storkel, 2001). Nouns and
      verbs, however, tend to differ in rate of acquisition, indicating that word
      learning mechanisms may differ across grammatical class. The purpose of the
      current study was to examine the effect of phonotactic probability on verb
      learning. Thirty-four typically developing preschool children participated in a
      multitrial word-learning task involving nonwords varying in phonotactic
      probability paired with unfamiliar actions. Multiple measures of word learning
      were obtained at increasing numbers of exposures. Correct responses were analyzed
      to examine rate of word learning. Results paralleled those of the previous noun
      learning study, with common sound sequences being learned more rapidly than rare
      sound sequences. The results are interpreted in relation to the effect of
      distributional regularities on acquisition and the reported discrepancy between
      noun and verb learning in English.

PMID- 14700358
TI  - A comparison of language abilities in adolescents with Down syndrome and children
      with specific language impairment.
AB  - This article compared the language profiles of adolescents with Down syndrome
      (DS) and children with specific language impairment matched for nonverbal
      cognitive ability, and investigated whether similar relationships could be
      established between language measures and other capacities in both groups.
      Language profiles were very similar: Expressive language was more affected than
      language comprehension, and grammar was more affected than vocabulary in both
      domains. Both groups were impaired on tests of grammatical morphology and
      phonological memory. There were some differences between the groups, but these
      could be attributed to other features of development of people with DS.

PMID- 14700359
TI  - Explaining and controlling regression to the mean in longitudinal research
      designs.
AB  - This tutorial is concerned with examining how regression to the mean influences
      research findings in longitudinal studies of clinical populations. In such
      studies participants are often obtained because of performance that deviates
      systematically from the population mean and are then subsequently studied with
      respect to change in the trait used for this selection. It is shown that in such
      research there is a potential for the estimates of change to be erroneous due to
      the effect of regression to the mean. The source of the regression effect is
      shown to arise from measurement error and a sampling bias of this measurement
      error in the process of selecting on extreme scores. It is also shown that
      regression effects are greater with measures that are less reliable and with
      samples that are selected with more extreme scores. Furthermore, it is shown that
      regression effects are particularly prominent when measures of change are based
      on changes in dichotomous states formed from quantitative, normally distributed
      traits. In addition to a formal analysis of the regression to the mean, the
      features of regression to the mean are demonstrated via a simulation.

PMID- 14700360
TI  - Auditory temporal order discrimination and backward recognition masking in adults
      with dyslexia.
AB  - The ability of 20 adult dyslexic readers to extract frequency information from
      successive tone pairs was compared with that of IQ-matched controls using
      temporal order discrimination and auditory backward recognition masking (ABRM)
      tasks. In both paradigms, the interstimulus interval (ISI) between tones in a
      pair was either short (20 ms) or long (200 ms). Temporal order discrimination was
      better for both groups of listeners at long than at short ISIs, but no group
      differences in performance were observed at either ISI. Performance on the ABRM
      task was also better at long than at short ISIs and was influenced by variability
      in masker frequency and by the spectral proximity of target and masker. The only
      significant group difference was found in one condition of the ABRM task when the
      target-masker interval was 200 ms, but this difference was not reliable when the
      measure was of optimal performance. Moderate correlations were observed between
      auditory thresholds and phonological skill for the sample as a whole and within
      the dyslexic and control groups. However, although a small subgroup of dyslexic
      listeners with poor phonology was characterized by elevated thresholds across the
      auditory tasks, evidence for an association between auditory and phonological
      processing skills was weakened by the finding of a subgroup of control listeners
      with poor auditory processing and normal phonological processing skills.

PMID- 14700361
TI  - Contributions of semantic and facial information to perception of nonsibilant
      fricatives.
AB  - Most studies have been unable to identify reliable acoustic cues for the
      recognition of the English nonsibilant fricatives [see text]. The present study
      was designed to test the extent to which the perception of these fricatives by
      normal-hearing adults is based on other sources of information, namely,
      linguistic context and visual information. In Experiment 1, target words
      beginning with /f/, /theta/, /s/, or [see text] were preceded by either a
      semantically congruous or incongruous precursor sentence. Results showed an
      effect of linguistic context on the perception of the distinction between /f/ and
      /theta/ and on the acoustically more robust distinction between /s/ and [see
      text]. In Experiment 2, participants identified syllables consisting of the
      fricatives [see text] paired with the vowels /i, a, u/. Three conditions were
      contrasted: Stimuli were presented with (a) both auditory and visual information,
      (b) auditory information alone, or (c) visual information alone. When errors in
      terms of voicing were ignored in all 3 conditions, results indicated that
      perception of these fricatives is as good with visual information alone as with
      both auditory and visual information combined, and better than for auditory
      information alone. These findings suggest that accurate perception of nonsibilant
      fricatives derives from a combination of acoustic, linguistic, and visual
      information.

PMID- 14700362
TI  - Responses to targets in the visual periphery in deaf and normal-hearing adults.
AB  - The purpose of this study was to compare the response times of deaf and normal
      hearing individuals to the onset of target events in the visual periphery in
      distracting and nondistracting conditions. Visual reaction times to peripheral
      targets placed at 3 eccentricities to the left and right of a center fixation
      point were measured in prelingually deafened adults and normal-hearing adults.
      Deaf participants responded more slowly than normal-hearing participants to
      targets in the near periphery in the nondistracting condition and to targets in
      the near and distant periphery when distracting stimuli were present. One
      interpretation of these findings is that deaf individuals may be more deliberate
      than normal-hearing individuals in responding to near peripheral events and to
      peripheral events that occur in the presence of distracting stimuli.

PMID- 14700363
TI  - Association of orofacial muscle activity and movement during changes in speech
      rate and intensity.
AB  - Understanding how orofacial muscle activity and movement covary across changes in
      speech rate and intensity has implications for the neural control of speech
      production and the use of clinical procedures that manipulate speech prosody. The
      present study involved a correlation analysis relating average lower-lip and jaw
      muscle activity to lip and jaw movement distance, speed, and duration. Recordings
      were obtained on orofacial movement, muscle activity, and the acoustic signal in
      3 normal speakers as they repeated a simple test utterance with targeted speech
      rates varying from 60% to 160% of their habitual rate and at targeted vocal
      intensities of -6 dB and +6 dB relative to their habitual intensity. Surface
      electromyographic (EMG) recordings were obtained with electrodes positioned to
      sample primarily the mentalis, depressor labii inferior, anterior belly of the
      digastric, and masseter muscles. Two-dimensional displacements of the lower lip
      and jaw in the midsagittal plane were recorded with an electromagnetic system.
      All participants produced linear changes in percent utterance duration relative
      to the auditory targets for speech rate variation. Intensity variations ranged
      from -10 dB to +8 dB. Average EMG levels for all 4 muscles were well correlated
      with specific parameters of movement. Across the intensity conditions, EMG level
      was positively correlated with movement speed and distance in all participants.
      Across the rate conditions, EMG level was negatively correlated with movement
      duration in all participants, while greater interparticipant variability was
      noted for correlations relating EMG to speed and distance. For intensity control,
      it is suggested that converging neural input to orofacial motoneurons varies
      monotonically with movement distance and speed. In contrast, rate control appears
      to be more strongly related to the temporal characteristics of neural input than
      activation level.

PMID- 14700364
TI  - Acoustic characteristics of the question-statement contrast in severe dysarthria
      due to cerebral palsy.
AB  - Studies of prosodic control in severe dysarthria (DYS) have focused on
      differences between impaired and nonimpaired speech in terms of the range and
      variation of fundamental frequency (F0), intensity, and duration. Whether
      individuals with severe DYS can adequately signal prosodic contrasts and which
      acoustic cues they use to do so has received far less attention. This article
      focused on the question-statement contrast. In nonimpaired speech, this contrast
      is believed to be cued primarily by F0, although some researchers have argued
      that duration also plays a role. This study examined how 8 speakers with severe
      DYS due to cerebral palsy signaled the question-statement contrast for a set of
      10 short phrases. An additional 8 healthy controls (HCs) produced the same set of
      phrases as questions and statements. To analyze the speech recordings, peak F0
      (F0peak), average F0 (F0ave), slope of F0 (F0slope), peak intensity (INTpeak),
      average intensity (INTave), slope of intensity (INTslope), and duration measures
      were calculated for each syllable (S1, S2, S3) within each phrase. Acoustic
      analyses revealed that speakers with DYS and HCs used F0, duration, and to a
      lesser degree, intensity cues to signal the contrast. Moreover, productions by
      speakers with DYS had longer and louder S3 for questions compared to productions
      by HCs, suggesting that speakers with DYS may have been compensating for their
      reduced ability to control F0 by exploiting their residual control of loudness
      and duration. Data from a previous perceptual study (R. Patel, 2002b) with the
      same speakers with DYS were used to analyze the relationship between acoustic
      characteristics and listener perceptions of their productions. Logistic
      regression analysis revealed that S1_F0ave; S2_duration; and S3_duration,
      S3_F0peak, S3_F0slope, S3_INTave, and S3_ INTslope were significant predictors of
      the perceived prosodic contrast. Identifying acoustic consistencies in prosodic
      control among speakers with DYS provides the impetus to build vocalization
      recognition algorithms that are capable of processing dysarthric speech for use
      in assistive communication aids. These findings suggest that speakers with DYS
      may also benefit from intervention aimed at improving prosodic control such that
      these contrasts may be exploited for communication.

PMID- 14700365
TI  - Oral breathing challenge in participants with vocal attrition.
AB  - Vocal folds undergo osmotic challenge by mouth breathing during singing,
      exercising, and loud speaking. Just 15 min of obligatory oral breathing, to dry
      the vocal folds, increases phonation threshold pressure (Pth) and expiratory
      vocal effort in healthy speakers (M. Sivasankar & K. Fisher, 2002). We questioned
      whether oral breathing is more detrimental to phonation in healthy participants
      with a history of temporary vocal attrition. The effects of a 15-min oral or
      nasal breathing challenge on Pth and perceived expiratory vocal effort were
      compared for participants reporting symptoms of vocal attrition (N = 18, ages 19
      38 years) and normal controls (N = 20, ages 19-33 years). Post-challenge
      prechallenge differences in Pth (deltaPth) and effort (deltaEffort) revealed that
      oral breathing, but not nasal breathing, increased Pth (p < .001 ) and effort (p
      < .001) at low, comfortable, and high pitch. deltaPth was significantly greater
      in participants with vocal attrition than in normal controls (p < .001). Nasal
      breathing reduced Pth for all controls but not for all participants reporting
      vocal attrition. deltaPth was significantly and linearly correlated with
      deltaEffort (rvocal attrition = .81, p < .001; rcontrol = .84, p < .001). We
      speculate that the greater increases in Pth in participants reporting vocal
      attrition may result from delayed or inadequate compensatory response to
      superficial laryngeal dehydration. Obligatory oral breathing may place voice
      users at risk for exacerbating vocal attrition. That sol layer depletion by
      obligatory oral breathing increased Pth and vocal effort provides support for the
      role of superficial hydration in maintaining ease of phonation.

PMID- 14700366
TI  - Phonological priming in picture naming of young children who stutter.
AB  - The purpose of this study was to assess the influence of phonological priming on
      the speech reaction time (SRT) of children who do (CWS) and who do not (CWNS)
      stutter during a picture-naming task. Participants were eighteen 3-5-year-old CWS
      (M = 50.67 months, SD = 11.83 months), matched in age and gender with 18 CWNS (M
      = 49.44 months, SD = 10.22 months). The picture-naming task required each child
      to name, one at a time, computer-presented, white-on-black line drawings of
      common, age-appropriate objects "as quickly as you can" during 3 different
      conditions: (a) no prime, (b) related prime, and (c) unrelated prime, with naming
      latency (alternatively referred to as SRT; in milliseconds) as the main dependent
      variable. Results indicated that all children exhibited faster or shorter SRTs
      during the related condition compared to the no prime condition. Similarly, SRT
      was influenced with advancing age for all children, with 5-year-olds exhibiting
      faster SRTs than 3-year-olds. Furthermore, CWNS, but not CWS, demonstrated a
      negative correlation between articulatory mastery and SRT. Findings were taken to
      suggest that phonological priming is a feasible procedure for studying the speech
      language planning and production of 3-5-year-old children and that preschool
      children who stutter, as a group, may have somewhat less well developed
      articulatory systems than preschool children who do not stutter.

PMID- 14700367
TI  - Comparison of transducers and intraoral placement options for measuring lingua
      palatal contact pressure during speech.
AB  - Two studies were completed that focused on instrumentation and procedural issues
      associated with measurement of lingua-palatal contact pressure (LPCP) during
      speech. In the first experiment, physical features and response characteristics
      of 2 miniature pressure transducers (Entran EPI-BO and Precision Measurement 60S)
      were evaluated to identify a transducer suitable for measuring LPCP during
      speech. The 2 transducers were comparable in terms of physical dimensions and
      most response characteristics. However, the Entran device was less affected by
      air temperature fluctuations, making it the more attractive option for speech
      LPCP measurement. In a second experiment, 3 methods of placing the Entran device
      in the mouth were compared. The 3 adhesion methods evaluated were (a) taping a
      transducer to the hard palate, (b) surface mounting on a mold of the palate, and
      (c) flush mounting on a mold of the palate. Directly taping the transducer to the
      alveolar ridge was the least acceptable option, as it resulted in changes in
      other aspects of speech production (consonant duration and centroid frequency of
      the burst/frication) suggesting that articulation was unduly altered. Direct
      taping was also rated as least acceptable by the speakers. Surface and flush
      mounting resulted in fewer changes in speech aerodynamic and acoustic parameters
      of /t/ and/s/ compared to the tape condition. Listener ratings also indicated
      less articulatory disturbance in the surface and flush mounting conditions
      compared to the tape condition. Surface mounting was technically easier than
      flush mounting and it allows for rapid repositioning of the transducer if needed.

PMID- 14700368
TI  - Development and testing of a portable vocal accumulator.
AB  - This research note describes the design and testing of a device for unobtrusive,
      long-term ambulatory monitoring of voice use, named the Portable Vocal
      Accumulator (PVA). The PVA contains a digital signal processor for analyzing
      input from a neck-placed miniature accelerometer. During its development,
      accelerometer recordings were obtained from 99 participants with normal or
      dysphonic voices. The recordings were used to (a) test the specifications and
      capabilities of the PVA for monitoring normal and dysphonic voices and (b)
      explore potentially useful displays for the large quantity of data generated by
      long-term monitoring. The current prototype PVA is pocket-sized (12 x 8.5 x 2
      cm), lightweight (200 g), and capable of sampling 11 hr of voice-use data,
      including estimates of fundamental frequency, sound pressure level, and phonation
      duration.

PMID- 14700369
TI  - Major problems with a revisit.

PMID- 14700371
TI  - Parent-reported language skills in relation to otitis media during the first 3
      years of life.
AB  - As part of a larger study of the potential impact of early-life otitis media (OM)
      on speech, language, cognition, and behavior, we studied the degree of
      association between parent-reported language scores at ages 1, 2, and 3 years and
      the cumulative duration of middle-ear effusion (MEE) during the first 3 years of
      life in a demographically diverse sample of 621 children. We estimated the
      cumulative percentage of days with MEE from prospective monthly observations of
      middle-ear status and interpolations for periods between visits. For each child,
      parents completed the appropriate inventory of the MacArthur Communicative
      Development Inventories (CDI; L. Fenson et al., 1993) at ages 1, 2, and 3 years.
      We also evaluated the contribution of maternal education, as a proxy for
      socioeconomic status, to scores on the parent reports. Scores on the new CDI-III
      (B. Oliver et al., in press) varied positively with sociodemographic variables
      and were significantly correlated with scores from the CDI used when the children
      were younger. Unadjusted correlations between scores at ages 1 and 2 years and
      the percentages of days with MEE in the respective antecedent periods were
      statistically nonsignificant or of questionable clinical importance. The
      correlations between parent-reported scores at age 3 years and children's
      cumulative percentage of days with MEE in Years 1, 2, and 3 combined ranged from 
      .187 to -.248 (all p values < .001). The percentage of days with MEE and maternal
      education each contributed independently to scores at age 3 years. In the light
      of other findings from the larger study, we think it likely that the negative
      associations between language measures and MEE reflect confounding factors that
      contribute, on the one hand, to the duration of OM in young children and, on the
      other hand, to slow development of their language skills.

PMID- 14700370
TI  - A family aggregation study: the influence of family history and other risk
      factors on language development.
AB  - Substantial evidence continues to accrue for familial transmission of specific
      language impairment (SLI). The incidence in families with a history of SLI is
      estimated at approximately 20%-40%, whereas in the general population the
      estimated incidence is about 4%. Typical aggregation studies compare data on the
      speech and language status of parents and siblings of individuals with SLI (the
      probands) to similar data from family members of control individuals with no
      speech or language disorder history. In the present study, family aggregation of
      SLI was examined for a unique sample of children who were ascertained before 6
      months of age and thus did not have SLI, but were born into a family with a
      positive history of SLI (FH+). No study to date has examined the pattern of
      affectance in families of children ascertained at such a young age. In addition,
      the ratio of boys to girls born into such families was investigated, as previous
      studies have suggested alterations in the expected gender ratios. Consistent with
      prior research, SLI was found to aggregate in families; the average affectance
      rate in FH+ families was 32%, with significantly more boys (41%) reported as
      having SLI than girls (16%). A comparison of FH+ and control families (FH-) on
      sociodemographic factors and medical history revealed differences in the overall
      rate of autoimmune diseases; FH+ families reported a significantly higher
      incidence (35%) compared to FH- families (9%). Finally, the 3-year language
      abilities of a subset of 32 children from FH+ families were compared with those
      of 60 children from FH- families. Children from FH+ families scored significantly
      lower on standardized measures of language and were more likely to fall below the
      16th percentile (28%) than children from FH- families (7%). These results provide
      converging evidence that children from FH+ families are indeed at greater risk of
      developing language delay compared to children from control families.

PMID- 14700373
TI  - The performance of typically developing 2 1/2-year-olds on dynamic display AAC
      technologies with different system layouts and language organizations.
AB  - The current generation of augmentative and alternative communication (AAC)
      technologies is largely based on conceptual models of adults who are not disabled
      (J. Light & P. Lindsay, 1991). As a result, there is a large "cost of learning"
      placed on young children. This paper presents the results of a study designed to
      investigate the learning demands of dynamic display systems that differed in
      system layout and language organization for children approximately 2 1/2 years
      old (2 years 5 months to 2 years 11 months). Thirty typically developing children
      were asked to locate 12 vocabulary items within a play context of a birthday
      party. Ten children were randomly assigned to each of 3 system approaches:
      vocabulary in a grid format organized taxonomically, vocabulary in a grid format
      organized schematically, and vocabulary in an integrated scene organized
      schematically. The children participated in 4 learning and testing sessions and 1
      generalization session. Results indicated that the children performed poorly in
      all conditions but were able to locate more vocabulary items in the schematic
      scene condition than the taxonomic grid or schematic grid conditions. There was
      evidence that the children failed to generalize their knowledge of the vocabulary
      to facilitate learning of novel vocabulary items. The current design of AAC
      dynamic display systems appears to be inappropriate for very young children.
      Rather than relying solely on technology for these young children, early
      intervention should target multiple modes of communication. AAC technologies
      should be redesigned to reduce learning demands. Results are discussed with
      implications for practice and suggestions for future research.

PMID- 14700372
TI  - Agrammatic comprehension of simple active sentences with moved constituents:
      Hebrew OSV and OVS structures.
AB  - This study examines agrammatic comprehension of object-subject-verb (OSV) and
      object-verb-subject (OVS) structures in Hebrew. These structures are
      syntactically identical to the basic order subject-verb-object (SVO) sentence
      except for the movement of the object to the beginning of the sentence, and thus
      enable empirical examination of syntactic movement in agrammatic comprehension.
      Seven individuals with agrammatism, 7 individuals with conduction aphasia, and 7
      individuals without language impairment, all native speakers of Hebrew, performed
      a sentence-picture matching task. The task compared OSV and OVS sentences to SVO
      sentences and to subject and object relatives. Individuals with agrammatism
      performed more poorly than those in either of the other groups. Their
      comprehension of SVO sentences was significantly above chance, but comprehension
      of OSV and OVS sentences was at chance and was poorer than comprehension of SVO
      sentences. These results show that agrammatic comprehension of structures that
      involve movement of a noun phrase is impaired even when the structure is a simple
      active sentence, in line with the Trace Deletion Hypothesis (TDH; Y. Grodzinsky,
      1990, 1995a, 2000). A modification is suggested to accommodate the TDH with the
      VP Internal Subject Hypothesis, according to which individuals with agrammatism
      use an "Avoid Movement" strategy in comprehension.

PMID- 14700374
TI  - Quick incidental verb learning in 4-year-olds: identification and generalization.
AB  - This study examined the abilities of young children to identify and generalize
      new verbs from an indirect teaching context. Forty 4-year-olds were shown a story
      that presented the following manner-of-motion verbs: frolic, saunter, scurry,
      strut, and trudge. The experimental group (N = 20) heard the label of each verb
      13 times while viewing the story, whereas the control group (N = 20) did not hear
      the verbs' labels. The performances of these two groups were compared to each
      other and to a group of adults (N = 22) who did not view the story but presumably
      had prior knowledge of the verbs. The experimental group correctly identified the
      target verbs in their prototypical form significantly more often than the control
      group but less often than the adult group. Generalization measures were evaluated
      for the children in the experimental group who correctly identified more than
      half of the target verbs (N = 6), their age-matched control group peers (N = 9),
      and the adult group. The experimental subgroup and the adults correctly
      generalized the verb labels to actions in which unimportant motion features had
      been altered. However, unlike the adult group, the experimental subgroup
      responded inconsistently to generalization questions in which important movement
      features of the actions had been altered. These results suggest that, even in
      their initial representations of manner-of-motion verbs, young children are
      sensitive to the relative importance of the different movements that make up
      these actions.

PMID- 14700375
TI  - Beginning to communicate after cochlear implantation: oral language development
      in a young child.
AB  - This longitudinal case study examined the emergence of a wide range of oral
      language skills in a deaf child whose cochlear implant was activated at 20
      months. The main purposes of this study were to determine "Hannah's" rate of
      spoken language development during her second to fourth year of implant
      experience and to estimate the efficiency of her progress by comparing her
      performance to that of typically developing children. Mother-child interactions
      were also examined to determine changes in Hannah's communication competence.
      Normal or above-normal rates of development were observed in the following areas:
      (a) decreased production of nonwords, (b) increased receptive vocabulary, (c)
      type-token ratio, (d) regular use of word combinations, and (e) comprehension of
      phrases. Below-normal rates of development were observed in the following areas:
      (a) speech intelligibility, (b) number of word types and tokens, and (c) mean
      length of utterance in morphemes. Analysis of parent-child interactions showed a
      large increase in responses to questions during the third year of implant use.
      Data from Hannah's first post-implantation year (D. J. Ertmer & J. A. Mellon,
      2001) indicated that some early language milestones were attained quite rapidly
      (e.g., canonical vocalizations and emergence of first word combinations). In
      contrast, the current study revealed that progress had slowed for related, but
      more advanced skills (e.g., production of intelligible speech and consistent use
      of word combinations). These changes in rate of development suggest that any
      advantages for language learning due to Hannah's advanced maturity (or other
      unknown factors) decreased with time and increasing linguistic complexity.

PMID- 14700376
TI  - Morphology in picture descriptions provided by persons with Alzheimer's disease.
AB  - The language of persons with Alzheimer's disease (AD) has been characterized by
      semantic-conceptual deterioration versus structural preservation, yet the
      research has not examined possible differentiation between syntactic and
      morphological knowledge. Taking advantage of the rich morphology of Hebrew, the
      current paper looks at these two aspects of grammatical knowledge in descriptions
      of the Cookie Theft picture. Speech samples were collected from 14 persons with
      AD and 48 elderly control participants and analyzed for semantic, syntactic, and
      morphological knowledge or difficulties. Analyses showed that although persons
      with AD conveyed less information and made more semantic errors than did control
      participants, their language remained structurally rich. Persons with AD used the
      same syntactic structures and the same morphological forms as control
      participants and made very few structural errors.

PMID- 14700377
TI  - Effectiveness of communication strategies used by caregivers of persons with
      Alzheimer's disease during activities of daily living.
AB  - Communication difficulties between individuals with Alzheimer's disease (AD) and
      their caregivers are commonly reported. Caregivers carry the burden of managing
      breakdowns in communication because people with AD are often unable to modify
      their communicative behavior. To assist caregivers in this endeavor, clinicians
      and caregiving professionals have offered a variety of strategies aimed at
      accommodating the individual's declining abilities. Many of these strategies are
      intuitively appealing, but they lack empirical support. This study investigated
      the effectiveness of 10 frequently recommended communication strategies when
      employed by family caregivers of persons with AD. In particular, we assessed (a)
      which strategies family caregivers report using and with what degree of success,
      (b) which of these strategies are used by caregivers in actual interactions with
      their spouses, and (c) which strategies contribute to improved communication. The
      study included a self-report questionnaire and wireless audio-recorded
      interactions between 18 persons with AD and their spousal caregivers during
      activities of daily living. The findings validate the effectiveness of certain
      communication strategies (e.g., simple sentences) but not others (e.g., slow
      speech). The results should be of interest to both family members and
      professionals who want to enhance communication and the quality of their
      interactions with persons with Alzheimer's disease.

PMID- 14700378
TI  - Repair behavior in children with intellectual impairments: evidence for
      metalinguistic competence.
AB  - This paper tested the prediction that children with cognitive impairments who can
      use language intentionally will be able to carry out the metalinguistic
      operations involved in speech monitoring and repair. The specific linguistic
      characteristics of responses to requests for clarification given by 4 children
      with lower than normal IQ, ages 3 years 5 months to 6 years 10 months, were
      investigated. The analysis focused on children's ability to locate the specific
      errors that provoked neutral requests for clarification and produce repair. Three
      children could locate their errors and partly succeed in providing repair. It is
      suggested that ability to perform metaprocedures such as are implicated in repair
      behavior may be preserved in children with intellectual disabilities and that
      this ability does not implicate conscious awareness, nor does it depend on mature
      linguistic competence.

PMID- 14700379
TI  - Unified treatment recommendations: a response to Rvachew and Nowak (2001).

PMID- 14700380
TI  - Talker and lexical effects on audiovisual word recognition by adults with
      cochlear implants.
AB  - The present study examined how postlingually deafened adults with cochlear
      implants combine visual information from lipreading with auditory cues in an open
      set word recognition task. Adults with normal hearing served as a comparison
      group. Word recognition performance was assessed using lexically controlled word
      lists presented under auditory-only, visual-only, and combined audiovisual
      presentation formats. Effects of talker variability were studied by manipulating
      the number of talkers producing the stimulus tokens. Lexical competition was
      investigated using sets of lexically easy and lexically hard test words. To
      assess the degree of audiovisual integration, a measure of visual enhancement,
      R(a), was used to assess the gain in performance provided in the audiovisual
      presentation format relative to the maximum possible performance obtainable in
      the auditory-only format. Results showed that word recognition performance was
      highest for audiovisual presentation followed by auditory-only and then visual
      only stimulus presentation. Performance was better for single-talker lists than
      for multiple-talker lists, particularly under the audiovisual presentation
      format. Word recognition performance was better for the lexically easy than for
      the lexically hard words regardless of presentation format. Visual enhancement
      scores were higher for single-talker conditions compared to multiple-talker
      conditions and tended to be somewhat better for lexically easy words than for
      lexically hard words. The pattern of results suggests that information from the
      auditory and visual modalities is used to access common, multimodal lexical
      representations in memory. The findings are discussed in terms of the
      complementary nature of auditory and visual sources of information that specify
      the same underlying gestures and articulatory events in speech.

PMID- 14700381
TI  - Tri-word presentations with phonemic scoring for practical high-reliability
      speech recognition assessment.
AB  - Speech recognition test reliability is optimized with 450 test items, and the
      Computer Assisted Speech Recognition Assessment (CASRA) test is a practical
      approach for achieving this goal by combining 50 presentations of 3 consonant
      vowel nucleus-consonant (CNC) words each with phonemic scoring (S. A. Gelfand,
      1998). However, optimized reliability might not be essential if reliability is as
      high as possible in light of practical constraints and what the clinician is
      trying to do with the results. The CASRA paradigm addresses these compromise
      goals with a reduced number of 3-word sets: 25 sets yield 25 (groups) x 3 (words)
      x 3 (phonemes) = 225 test items, 20 sets give 20 x 3 x 3 = 180 items, and 10 sets
      provide 10 x 3 x 3 = 90 items. This study addressed the empirical reliability of
      such an approach, and the extent to which results on shortened versions predict
      full-test scores. Test and retest scores were obtained for 10-, 20-, and 25-set
      versions of the CASRA for 144 participants with a wide range of hearing ability.
      For group data, first and second scores were highly correlated and not
      significantly different from each other for all 3 test sizes. Performance based
      on 20 and 25 sets accounted for roughly 97% of the variance of full (50-set) test
      scores, and scores based on 10 sets accounted for about 88% of the full-test
      variance. Individual test-retest reliability agreed with theoretical expectations
      based on 95% binomial confidence intervals. Cases outside the 95% confidence
      limits were 7.6% for 10 sets, and 3.5% for 20 and 25 sets with phoneme scoring,
      and 4.9% for 10 and 20 sets and 3.5% for 25 sets with word scoring. The shortened
      CASRA is a practical way to achieve improvements in reliability over traditional
      word tests. The 20-set version may approximate the strongest compromise when
      trying to shorten test size without appreciably reducing reliability for clinical
      purposes. However, the 10-set version is probably a more practical approach for
      routine use because it accounts for 88% of full-test variance, is more reliable
      than a traditional 75-word test, and does not appear to be subject to significant
      short-term learning effects.

PMID- 14700382
TI  - Perceptual normalization for inter- and intratalker variation in Cantonese level
      tones.
AB  - Inter- and intratalker variation in the production of lexical tones may
      contribute to acoustic overlap among tone categories. The present study
      investigated whether such category overlap gives rise to perceptual ambiguity
      and, if so, whether listeners are able to reduce this ambiguity using contextual
      information. In the first experiment, native Cantonese-speaking listeners were
      asked to identify isolated Cantonese level tones produced by 7 talkers.
      Identification accuracy was significantly higher when the presentation of items
      was blocked by talker rather mixed across talkers. In the second experiment,
      listeners identified the final (target) tone of 6-syllable semantically neutral
      sentences with f0 patterns of the context (i.e., the first 5 syllables) altered.
      The same target tone was identified differently depending on the context. In the
      third experiment, the context portions of stimulus sentences from the second
      experiment were divided into 2 halves, and their f0 patterns were altered
      independently. In identifying the target tone, listeners relied more heavily on
      the f0 pattern of the second (last) half of the context. These results are
      discussed in relation to characteristic inter- and intratalker variations of
      lexical tones.

PMID- 14700383
TI  - Do vocal warm-up exercises alleviate vocal fatigue?
AB  - Vocal warm-up (WU) exercises of varying types and durations have been suggested
      as a way of improving vocal function. However, limited research has been
      conducted to assess the effects of vocal WU exercises on normal or disordered
      voices. This study attempted to manipulate vocal function, assessed by phonation
      threshold pressure (PTP) and self-perceived phonatory effort (PPE) at 3 pitches,
      in 8 young women who reported symptoms of chronic vocal fatigue. Predictions were
      that PTP and PPE would decrease after 20 min of vocal WU exercises, increase
      after 1 hr of loud reading, and decrease after 30 min of vocal silence.
      Furthermore, greater increases in PTP and PPE were expected when the loud-reading
      task was preceded by a placebo condition of vocal rest than by vocal WU
      exercises. Results failed to reveal statistically significant changes in PTP or
      PPE after any of the experimental tasks. High between-subject variability
      contributed to this result. Removal of 1 outlier from the sample resulted in a
      statistically significant difference for PTP across tasks, although post hoc
      pairwise comparisons failed to detect specific effects. Informal inspection of
      the data indicated that the most obvious difference was an increase in PTP after
      the loud-reading task at the highest pitch.

PMID- 14700384
TI  - Evidence of motor programming deficits in children diagnosed with DAS.
AB  - In this study the hypothesis of motor programming involvement in developmental
      apraxia of speech (DAS) was investigated by studying articulatory compensation.
      Five children with DAS and 5 normally speaking children (age 5;0 [years;months]
      to 6;10), and 6 adult women produced utterances in a normal speaking condition
      and in a bite-block condition in which the mandible was kept in a fixed position.
      Throughout the utterances, the course of the second formant was used to determine
      articulatory compensation and the effect of the bite block on anticipatory
      coarticulation. Results showed that the bite-block condition in normally speaking
      children, like in adult women, did not affect the extent of anticipatory
      coarticulation. In the speech of children with DAS, the bite block had large
      effects on coarticulatory patterns and on vowel quality, which, contrary to
      expectations, had improved. These results are interpreted as a clear
      demonstration of deficient motor programming in DAS.

PMID- 14700385
TI  - Perception of place of articulation by children with cleft palate and posterior
      placement.
AB  - The aim of this study was to determine if children with repaired cleft palate who
      demonstrate posterior placement of alveolar targets (e.g., /t(h)/ --> [k(h)]),
      known as Group P, differ from children with cleft palate without such an error
      pattern (Group NP) and from normally developing children without cleft palate
      (Group N) in the perception of /t(h)/ and /k(h)/. Ten age-matched children in
      each of these three groups identified 8 synthetic stimuli along an acoustic
      continuum ranging from /t(h)/ to /k(h)/. The children with posterior placement
      performed at random levels, appearing unable to distinguish /t(h)/ from /k(h)/.
      In contrast, both groups of children without posterior placement demonstrated a
      clear identification pattern. These results, which suggest that children with
      cleft palate and posterior placement have a perceptual deficit, contribute to
      discussion of the possible etiology of speech deficits in this population.

PMID- 14700386
TI  - Implementing speech supplementation strategies: effects on intelligibility and
      speech rate of individuals with chronic severe dysarthria.
AB  - A growing body of experimental research suggests that speech supplementation
      strategies can markedly increase speech intelligibility for individuals with
      dysarthria (D. Beukelman & K. Yorkston, 1977; E. Crow & P. Enderby, 1989; L.
      Hunter, T. Pring, & S. Martin, 1991; K. C. Hustad & D. R. Beukelman, 2001).
      However, studies in which speech supplementation strategies were actually
      implemented by speakers with dysarthria are limited, leaving their clinical
      efficacy unknown. The present study compared intelligibility and speech rate
      differences following speaker implementation of 3 strategies (topic, alphabet,
      and combined topic and alphabet supplementation) and a habitual (noncued) speech
      control condition for 5 speakers with severe dysarthria. Results revealed that
      combined cues and alphabet cues yielded significantly higher intelligibility
      scores and slower speech rates than topic cues and noncued speech. Overall, topic
      cues and noncued speech did not differ from one another with regard to
      intelligibility or speech rate. Combined cues and alphabet cues did not differ
      from one another with regard to intelligibility; however, speech rate was
      significantly different between the 2 strategies. Individual differences among
      speakers were generally consistent with group findings. Results were somewhat
      different from previous research in which strategies were experimentally
      superimposed on the habitual speech signal. However, findings provide evidence
      that alphabet cues and combined cues can have an important effect on
      intelligibility for speakers with severe dysarthria.

PMID- 14700387
TI  - Quantitative and graphic acoustic analysis of phonatory modulations: the
      modulogram.
AB  - A method is presented for analyzing phonatory instabilities that occur as
      modulations of fundamental frequency (f0) and sound pressure level (SPL) on the
      order of 0.2 to 20 cycles per second. Such long-term phonatory instabilities,
      including but not limited to traditional notions of tremor, are distinct from
      cycle-to-cycle perturbation such as jitter or shimmer. For each of the 2
      parameters (f0, in Hz, and SPL, in dB), 3 frequency domains are proposed: (a)
      flutter (10-20 Hz), (b) tremor (2-10 Hz), and (c) wow (0.2-2.0 Hz), yielding 6
      types of instability. Analyses were implemented using fast Fourier transforms
      (FFTs) with domain-specific analysis parameters. Outputs include a graphic
      display in the form of a set of low-frequency spectrograms (the "modulogram") and
      quantitative measures of the frequencies, magnitudes, durations, and sinusoidal
      form of the instabilities. An index of a given instability is developed by
      combining its duration and average modulation magnitude into a single quantity.
      Performance of the algorithms was assessed by analyzing test signals with known
      degrees of modulation, and a range of applications was reviewed to provide a
      rationale for use of modulograms in phonatory assessment.

PMID- 14700388
TI  - DNA microarray gene expression analysis of a vocal fold polyp and granuloma.
AB  - Genome-wide transcriptional profiling has important applications in advancing
      knowledge of vocal fold biology. With the use of DNA microarray technology,
      analysis of global patterns of gene expression can reveal unexpected networks of
      coordinated regulation in the extracellular matrix of the lamina propria.
      Transcriptional gene expression patterns for 2 vocal fold pathologies--vocal fold
      polyp (VP; N = 1) and vocal fold granuloma (VG; N = 1) were analyzed by means of
      DNA microarray analysis for 4,632 human genes using another patient's true vocal
      fold (TVF; N = 1) as a control. Twenty-four and 29 genes for VG and VP,
      respectively, were established to be either over- or underexpressed compared to
      that of TVF. Five-way cluster analysis revealed broad patterns that suggest a
      potential degree of organization underlying gene expression in these tissues. For
      the 1 VG, genes involved represent inflammation and wound healing; for the 1 VP,
      involved genes demonstrate a tempered wound repair response and increased
      epithelial manifestations. These results successfully demonstrate the use of DNA
      microarray technology as a new approach for further investigations dissecting
      vocal fold disease. Further investigation is needed on larger sample sizes to
      establish transcriptional gene expression patterns for VP and VG.

PMID- 14700389
TI  - Is listener comfort a viable construct in stuttering research?
AB  - This article reports the development of a tool for measuring how comfortable a
      person feels when communicating with someone who has undergone treatment for
      stuttering. The person rates the speaker on a 9-point Listener Comfort Scale (9 =
      extremely comfortable, 1 = extremely uncomfortable). In a preliminary
      investigation of the reliability and validity of the scale, 15 unsophisticated
      listeners rated video recordings of 10 adults before and after a prolonged-speech
      treatment for stuttering and of 10 matched controls. The results were compared
      with those of another 15 listeners who rated the same recordings with the widely
      used 9-point Speech Naturalness Scale (R. R. Martin, S. K. Haroldson, & K. A.
      Triden, 1984). Results showed that reliability of the Speech Naturalness Scale
      was superior to the Listener Comfort Scale, although users of both scales were
      able to distinguish between pretreatment speech, posttreatment speech, and the
      speech of controls. The results suggest that the Listener Comfort Scale captures
      information that is somewhat different than the information captured by the
      Speech Naturalness Scale. The authors concluded that the concept of listener
      comfort is a potentially useful additional way of investigating the social
      validity of behavioral treatments for stuttering.

PMID- 14700390
TI  - At the feet of the dinosaurs: the early history and radiation of lizards.
AB  - Lizards, snakes and amphisbaenians together constitute the Squamata, the largest
      and most diverse group of living reptiles. Despite their current success, the
      early squamate fossil record is extremely patchy. The last major survey of
      squamate palaeontology and evolution was published 20 years ago. Since then,
      there have been major changes in systematic theory and methodology, as well as a
      steady trickle of new fossil finds. This review examines our current
      understanding of the first 150 million years of squamate evolution in the light
      of the new data and changing ideas. Contrary to previous reports, no squamate
      fossils are currently documented before the Jurassic. Nonetheless, indirect
      evidence predicts that squamates had evolved by at least the middle Triassic, and
      had diversified into existing major lineages before the end of this period. There
      is thus a major gap in the squamate record at a time when key morphological
      features were evolving. With the exception of fragmentary remains from Africa and
      India, Jurassic squamates are known only from localities in northern continents
      (Laurasia). The situation improves in the Early Cretaceous, but the southern
      (Gondwanan) record remains extremely poor. This constrains palaeobiogeographic
      discussion and makes it difficult to predict centres of origin for major squamate
      clades on the basis of fossil evidence alone. Preliminary mapping of
      morphological characters onto a consensus tree demonstrates stages in the
      sequence of acquisition for some characters of the skull and postcranial
      skeleton, but many crucial stages--most notably those relating to the acquisition
      of squamate skull kinesis--remain unclear.

PMID- 14700391
TI  - Potential mechanisms of avian sex manipulation.
AB  - The aim of this review is to consider the potential mechanisms birds may use to
      manipulate the sex of their progeny, and the possible role played by maternal
      hormones. Over the past few years there has been a surge of reports documenting
      the ability of birds to overcome the rigid process of chromosomal sex
      determination. However, while many of these studies leave us in little doubt that
      mechanisms allowing birds to achieve this feat do exist, we are only left with
      tantalizing suggestions as to what the precise mechanism or mechanisms may be.
      The quest to elucidate them is made no easier by the fact that a variety of
      environmental conditions have been invoked in relation to sex manipulation, and
      there is no reason to assume that any particular mechanism is conserved among the
      vast diversity of species that can achieve it. In fact, a number of intriguing
      proposals have been put forward. We begin by briefly reviewing some of the most
      recent examples of this phenomenon before highlighting some of the more plausible
      mechanisms, drawing on recent work from a variety of taxa. In birds, females are
      the heterogametic sex and so non-Mendelian segregation of the sex chromosomes
      could conceivably be under maternal control. Another suggestion is that follicles
      that ultimately give rise to males and females grow at different rates.
      Alternatively, the female might selectively abort embryos or 'dump lay' eggs of a
      particular sex, deny certain ova a chance of ovulation, fertilization or zygote
      formation, or selectively provision eggs so that there is sex-specific embryonic
      mortality. The ideas outlined in this review provide good starting points for
      testing the hypotheses both experimentally (behaviourally and physiologically)
      and theoretically.

PMID- 14700392
TI  - The use of multiple cues in mate choice.
AB  - An increasing number of studies find females to base their mate choice on several
      cues. Why this occurs is debated and many different hypotheses have been
      proposed. Here I review the hypotheses and the evidence in favour of them. At the
      same time I provide a new categorisation based on the adaptiveness of the
      preferences and the information content of the cues. A few comparative and
      empirical studies suggest that most multiple cues are Fisherian attractiveness
      cues or uninformative cues that occur alongside a viability indicator and
      facilitate detection, improve signal reception, or are remnants from past
      selection pressures. However, much evidence exists tor multiple cues providing
      additional information and serving as multiple messages that either indicate
      general mate quality or enable females that differ in mate preferences to choose
      the most suitable male. Less evidence exists for multiple cues serving as back-up
      signals. The importance of receiver psychology, multiple sensory environments and
      signal interaction in the evolution of multiple cues and preferences has received
      surprisingly little attention but may be of crucial importance. Similarly, sexual
      conflict has been proposed to result in maladaptive preferences for manipulative
      cues, and in neutral preferences for threshold cues, but no reliable evidence
      exists so far. An important factor in the evolution of multiple preferences is
      the cost of using additional cues. Most theoretical work assumes that the cost of
      choice increases with the number of cues used, which restricts the conditions
      under which preferences for multiple cues are expected to evolve. I suggest that
      in contrast to this expectation, the use of multiple cues can reduce mate choice
      costs by decreasing the number of mates inspected more closely or the time and
      energy spent inspecting a set of mates. This may be one explanation for why
      multiple cues are more common than usually expected. Finally I discuss the
      consequences that the use of multiple cues may have for the process of sexual
      selection, the maintenance of genetic variation, and speciation.

PMID- 14700393
TI  - The radiation of the Cape flora, southern Africa.
AB  - The flora of the south-western tip of southern Africa, the Cape flora, with some
      9000 species in an area of 90,000 km2 is much more speciose than can be expected
      from its area or latitude, and is comparable to that expected from the most
      diverse equatorial areas. The endemism of almost 70%, on the other hand, is
      comparable to that found on islands. This high endemism is accounted for by the
      ecological and geographical isolation of the Cape Floristic Region, but
      explanations for the high species richness are not so easily found. The high
      species richness is accentuated when its taxonomic distribution is investigated:
      almost half of the total species richness of the area is accounted for by 33
      'Cape floral clades'. These are clades which may have initially diversified in
      the region, and of which at least half the species are still found in the Cape
      Floristic Region. Such a high contribution by a very small number of clades is
      typical of island floras, not of mainland floras. The start of the radiation of
      these clades has been dated by molecular clock techniques to between 18 million
      years ago (Mya) (Pelargonium) and 8 Mya (Phylica), but only six radiations have
      been dated to date. The fossil evidence for the dating of the radiation is shown
      to be largely speculative. The Cenozoic environmental history of southern Africa
      is reviewed in search of possible triggers for the radiations, climatic changes
      emerge as the most likely candidate. Due to a very poor fossil record, the
      climatic history has to be inferred from larger scale patterns, these suggest
      large-scale fluctuations between summer wet (Palaeocene, Early Miocene) and
      summer dry climates (Oligocene, Middle Miocene to present). The massive
      speciation in the Cape flora might be accounted for by the diverse limitations to
      gene flow (dissected landscapes, pollinator specialisation, long flowering times
      allowing much phenological specialisation), as well as a richly complex
      environment providing a diversity of selective forces (geographically variable
      climate, much altitude variation, different soil types, rocky terrain providing
      many micro-niches, and regular fires providing both intermediate disturbances, as
      well as different ways of surviving the fires). However, much of this is based on
      correlation, and there is a great need for (a) experimental testing of the
      proposed speciation mechanisms, (b) more molecular clock estimates of the age and
      pattern of the radiations, and (c) more fossil evidence bearing on the past
      climates.

PMID- 14700394
TI  - Parasitic exploitation as an engine of diversity.
AB  - Parasitic exploitation occurs within and between a wide variety of taxa in a
      plethora of diverse contexts. Theoretical and empirical analyses indicate that
      parasitic exploitation can generate substantial genetic and phenotypic
      polymorphism within species. Under some circumstances, parasitic exploitation may
      also be an important factor causing reproductive isolation and promoting
      speciation. Here we review research relevant to the relationship between
      parasitic exploitation, within species-polymorphism, and speciation in some of
      the major arenas in which such exploitation has been studied. This includes
      research on the vertebrate major histocompatibility loci, plant-pathogen
      interactions, the evolution of sexual reproduction, intragenomic conflict, sexual
      conflict, kin mimicry and social parasitism, tropical forest diversity and the
      evolution of language. We conclude by discussing some of the issues raised by
      comparing the effect of parasitic exploitation on polymorphism and speciation in
      different contexts.

PMID- 14700395
TI  - An experimental study on the vasoconstriction effect of calcium hydroxide using
      rat mesentery.
AB  - Calcium hyroxide has been used for eliminating persistent intracanal exudation.
      In order to address the mechanism behind this action, we investigated whether
      calcium hydroxide solutions cause the constriction of microvessels in the
      mesenteric microcirculation bed of rats. The exteriorised mesentery from
      anaesthetised rats was spread in a chamber, and arterioles, venules and
      capillaries were viewed under a digital microscope. Various concentrations of
      calcium hydroxide solutions were applied for 10 sec, and the diameter of the
      microvessels was recorded. In arterioles, calcium hydroxide solutions caused
      rapid and transient constriction. A statistically significant difference versus
      original diameter was detected 1 min after the application of 4.0 x 10(-3) mol/l
      and 1.0 x 10(-2) mol/l solutions (p < 0.05, one-way analysis of variance and
      Tukey-Kramer test). No statistically significant constriction occurred in
      capillaries and venules. It was concluded that the arteriolar constriction might
      be an explanation for the exudation-controlling effect of intracanal calcium
      hyroxide dressings.

PMID- 14700396
TI  - Contemporary perspectives on post-core systems.
AB  - The challenge of restoring endodontically-treated teeth has spawned a
      considerable diversity in foundation restorations and a plethora of publications
      in the dental literature. Moreover, it seems that an inverse relationship has
      developed between the escalating complexity in selecting a post-core system and
      the volume of reliable scientific data upon which clinicians base their treatment
      decisions. In the quest to restore aesthetics, function, and reduce the risk of
      treatment failure there is now a much greater emphasis on the preservation of
      sound tooth structure, tooth isolation for intracanal procedures, sealing the
      root canal and adapting the advantages and limitations of dental materials to the
      presenting clinical situation. The relatively recent introduction of metal-free
      posts into mainstream prosthodontics has added an aesthetic dimension to
      treatment planning. New adhesive systems and resin-based luting agents have the
      potential to create a genuine adhesive continuum between the tooth and post-core
      complex. While these developments may have significant ramifications with respect
      to treatment prognosis, the long-term clinical performance of contemporary post
      core systems is unclear.

PMID- 14700397
TI  - An in vitro study of coronal microleakage in endodontically-treated teeth
      restored with posts.
AB  - Coronal microleakage has received considerable attention as a factor related to
      failure of endodontic treatment and much emphasis is placed on the quality of the
      final restoration. Posts are frequently used for the retention of coronal
      restorations. These can be custom-made or prefabricated. Many authors have
      examined coronal microleakage with respect to gutta-percha root fillings and
      plastic coronal restorations, but few have investigated the coronal seal afforded
      by various post systems. The seal provided by a cemented post depends on the seal
      of the cement used. The purpose of this study was to compare coronal microleakage
      around cast and prefabricated posts using a dye-penetration method. Sixty
      extracted single-rooted human teeth were chemomechanically prepared. The root
      canals were filled with gutta-percha and sealer and they were then prepared for
      standard posts. Six groups, each of 10 teeth, were restored with either cast post
      or prefrabricated post. The posts were cemented with either glass ionomer cement
      (GIC), Variolink II or Durelon. The teeth were thermocycled and placed in Indian
      ink for one week. They were then demineralised and rendered transparent. Linear
      coronal dye penetration around the post was measured and compared. The least dye
      penetration was observed in roots restored with a cast post and Variolink II.
      Dentatus posts demonstrated the most microleakage. It appears that the dentine
      bonding cements have less microleakage than the traditional, non-dentine-bonding
      cements and adaptation of the post with the canal may be more important than the
      cement used.

PMID- 14700398
TI  - Carious pulpitis: microbiological and histopathological considerations.
AB  - Dental caries is the result of microbial activities that induce the progressive
      localised destruction of teeth. Without treatment, this eventually results in
      infection of the dental pulp and surrounding periapical tissues. Although the
      bacteria responsible for caries initiation and early caries progression have been
      extensively studied, the microbiology of dentine caries reportedly shows
      considerable diversity and the associated microflora has not yet been fully
      identified. A search of the literature shows that few studies have analysed the
      microbiology of deep caries or examined the relationship between this microflora
      and the histopathology of chronic pulpitis in symptomatic teeth. The majority of
      the studies investigating the microbiology of carious dentine have used
      traditional culture methodology that has been reported to be fraught with
      difficulties and to underestimate the microbial populations. However, recent work
      using new technology in the form of Polymerase Chain Reaction (PCR) has shown
      potential by enhancing the identification and quantification of bacteria from
      complex environments. Application of this technology to carious dentine has
      identified an environment dominated by anaerobic organisms and containing
      significant numbers of Gram-negative bacteria that have been strongly implicated
      in endodontic infections subsequent to carious pulpitis. Examination of the
      histopathology of pulp sections from teeth extracted as a result of carious
      pulpitis showed pulpal reactions ranging from minimal inflammation to marked
      inflammatory infiltration of the pulp tissue. Of interest, were hard and soft
      tissue pathologic changes noted in the pulp tissues resulting from the combined
      effects of the carious microorganisms and the host tissue response. Improved
      knowledge of the microbial species associated with pulpitis could create the
      potential for development of diagnostic tools and restorative materials with
      appropriate antimicrobial properties.

PMID- 14700399
TI  - Recent advances in therapeutic exercise for the neck: implications for patients
      with head and neck pain.
AB  - There have been recent advances in the rehabilitation of the muscles that control
      the head and neck. These advances are based on evidence of specific neck muscle
      dysfunction in individuals with persistent head and neck pain. Traditional
      rehabilitation strategies have focused predominantly on muscle strength and
      endurance under high loads. New evidence suggests that in people with neck pain
      there are underlying neuromuscular problems that may require more immediate
      attention and may not be adequately addressed by simple strength and high-load
      endurance retraining. Evidence of altered coordination between the deep and
      superficial neck muscles, greater neck muscle fatigue under sustained low loads,
      and deficits in kinaesthetic sense have been identified in symptomatic
      individuals. There is evidence to indicate that addressing these muscle control
      problems, with specific gentle exercise strategies, results in a reduction in
      neck pain and associated symptoms.

PMID- 14700400
TI  - Should endodontic files be single-use only? A position paper from the Australian
      and New Zealand Academy of Endodontists.

PMID- 14700401
TI  - Studies of bloodstream infection outcomes: reading between the lines.

PMID- 14700402
TI  - Vascular catheters inserted in the trenches versus guideline documents: can the
      discrepancies be resolved?

PMID- 14700403
TI  - Role of comorbidity in mortality related to Staphylococcus aureus bacteremia: a
      prospective study using the Charlson weighted index of comorbidity.
AB  - OBJECTIVE: To demonstrate the effectiveness of the Charlson weighted index of
      comorbidity (WIC) for controlling comorbidity in prospective studies focusing on
      mortality in patients with Staphylococcus aureus bacteremia (SAB). DESIGN: Cohort
      study. SETTING: Two tertiary-care, university-affiliated hospitals in France.
      PATIENTS: One hundred sixty-six inpatients 18 years or older consecutively
      diagnosed with SAB from May 15, 2001, to May 15, 2002. METHODS: Patients were
      prospectively assessed and cases were followed by the infectious diseases consult
      service at least 3 months after effective antibiotic therapy completion. The
      Charlson WIC was computed and dichotomized into scores of fewer than 3 points and
      3 or more points. Bacteremia source, acute complication due to SAB acquisition in
      the ICU, and inappropriate empiric antibiotic therapy were recorded. The endpoint
      was death due to SAB and overall mortality. RESULTS: In univariate analysis, the
      Charlson WIC was able to predict overall mortality and S. aureus-related death.
      The following variables were found to be independently predictive of mortality
      due to SAB using the Cox model: an acute complication due to S. aureus (OR, 8.9;
      CI95, 4 to 19.7; P < .001), a Charlson WIC score of 3 or more (OR, 3; CI95, 1.3
      to 5.5; P = .006), and age (OR, 1.04; CI95, 1.009 to 1.07; P < .01). CONCLUSIONS:
      Comorbidity contributes to death in patients with SAB. The Charlson WIC is a good
      predictor of mortality in this population and may be a useful instrument to
      control comorbidity in studies aiming to investigate risk factors for death due
      to bacteremia.

PMID- 14700404
TI  - Outcomes of Hickman catheter salvage in febrile neutropenic cancer patients with
      Staphylococcus aureus bacteremia.
AB  - OBJECTIVE: To evaluate the outcome of attempted Hickman catheter salvage in
      neutropenic cancer patients with Staphylococcus aureus bacteremia who were not
      using antibiotic lock therapy. DESIGN: Retrospective cohort study. SETTING: A
      university-affiliated, tertiary-care hospital with 1,500 beds for adult patients.
      PATIENTS: All neutropenic cancer patients who had a Hickman catheter and S.
      aureus bacteremia (32 episodes in 29 patients) between January 1998 and March
      2002. METHODS: Salvage attempts were defined as cases where the Hickman catheter
      was not removed until we obtained the results of follow-up blood cultures
      performed 48 to 72 hours after starting treatment with antistaphylococcal
      antibiotics. Salvage was considered to be successful if the Hickman catheter was
      still in place 3 months later without recurrent bacteremia or death. RESULTS:
      Catheter salvage was attempted in 24 (75%) of the 32 episodes. Of the salvage
      attempts, the success rate was 50% (12 of 24). Salvage attempts were successful
      in 14% (1 of 7) of the episodes with positive follow-up blood cultures, and in
      65% (11 of 17) of those with negative follow-up blood cultures (P = .07). If the
      analysis is confined to cases with no external signs of catheter infection,
      salvage attempts were successful in 14% (1 of 7) of the episodes with positive
      follow-up blood cultures and in 80% (8 of 10) of those with negative follow-up
      blood cultures (P = .02). CONCLUSION: In neutropenic cancer patients with S.
      aureus bacteremia, attempted catheter salvage without antibiotic lock therapy was
      successful in 50% of the cases.

PMID- 14700405
TI  - Outcomes of nosocomial bloodstream infections in adult neutropenic patients: a
      prospective cohort and matched case-control study.
AB  - OBJECTIVE: To examine the clinical and epidemiologic features, excess length of
      stay, extra costs, and mortality attributable to bloodstream infection (BSI) in
      neutropenic patients with hematologic malignancies. DESIGN: Prospective cohort
      and matched case-control study. PATIENTS: All adult neutropenic patients with
      hematologic malignancies admitted to Cologne University Hospital between May 1,
      1997, and April 30, 1998, were prospectively observed. Case-patients were defined
      as patients with nosocomial BSI; control-patients were selected among patients
      without BSI. RESULTS: During the study period, the BSI rate in neutropenic
      patients was 14.3 per 100 neutropenic episodes. Eighty-four case-patients were
      included. Matching was successful for 96% of the cohort; 81 matched pairs were
      studied. The mean total length of stay was significantly longer for patients with
      BSI than for control-patients (37 vs 29 days; P = .002). Extra costs attributable
      to the infection averaged 3,200 dollars (U.S.) per patient. The crude mortality
      rates of case-patients and control-patients were 16% and 4%, respectively (P =
      .013), with an attributable mortality of 12% (odds ratio, 11). Eighty-seven
      percent of patients met the criteria for sepsis according to the American College
      of Chest Physicians/Society of Critical Care Medicine. Severe sepsis or septic
      shock occurred in 13% of patients and was correlated with mortality (55% vs 10%
      in patients without severe sepsis or septic shock; P = .01). CONCLUSIONS:
      Nosocomial BSI in neutropenic patients is significantly associated with an excess
      length of hospital stay, extra costs, and excess mortality. Severe sepsis and
      septic shock are closely correlated with an adverse outcome.

PMID- 14700406
TI  - Absence of excess mortality in critically ill patients with nosocomial
      Escherichia coli bacteremia.
AB  - OBJECTIVE: To evaluate excess mortality in critically ill patients with
      Escherichia coli bacteremia after adjustment for severity of illness. DESIGN:
      Retrospective (1992-2000), pairwise-matched (1:2), risk-adjusted cohort study.
      SETTING: Fifty-four-bed ICU in a university hospital including a medical and
      surgical ICU, a unit for care after cardiac surgery, and a burns unit. PATIENTS:
      ICU patients with nosocomial E. coli bacteremia (defined as cases; n = 64) and
      control-patients without nosocomial bloodstream infection (n = 128). METHODS:
      Case-patients were matched with control-patients on the basis of the Acute
      Physiology and Chronic Health Evaluation (APACHE) II system: an equal APACHE II
      score (+/- 2 points) and diagnostic category. In addition, control-patients were
      required to have an ICU stay at least as long as that of the respective case
      patients prior to onset of the bacteremia. RESULTS: The overall rate of
      appropriate antibiotic therapy in patients with E. coli bacteremia was high (93%)
      and such therapy was initiated soon after onset of the bacteremia (0.6 +/- 1.0
      day). ICU patients with E. coli bacteremia had more acute renal failure. No
      differences were noted between case-patients and control-patients in incidence of
      acute respiratory failure, hemodynamic instability, or age. No differences were
      observed in length of mechanical ventilation or length of ICU stay. In-hospital
      mortality rates for cases and controls were not different (43.8% and 45.3%,
      respectively; P = .959). CONCLUSION: After adjustment for disease severity and
      acute illness and in the presence of adequate antibiotic therapy, no excess
      mortality was found in ICU patients with E. coli bacteremia.

PMID- 14700407
TI  - Effect of nurse staffing and antimicrobial-impregnated central venous catheters
      on the risk for bloodstream infections in intensive care units.
AB  - BACKGROUND: Defining risk factors for central venous catheter (CVC)-associated
      bloodstream infections (BSIs) is critical to establishing prevention measures,
      especially for factors such as nurse staffing and antimicrobial-impregnated CVCs.
      METHODS: We prospectively monitored CVCs, nurse staffing, and patient-related
      variables for CVC-associated BSIs among adults admitted to eight ICUs during 2
      years. RESULTS: A total of 240 CVC-associated BSIs (2.8%) were identified among
      4,535 patients, representing 8,593 CVCs. Antimicrobial-impregnated CVCs reduced
      the risk for CVC-associated BSI only among patients whose CVC was used to
      administer total parenteral nutrition (TPN, 2.6 CVC-associated BSIs per 1,000 CVC
      days vs no TPN, 7.5 CVC-associated BSIs per 1,000 CVC-days; P = .006). Among
      patients not receiving TPN, there was an increase in the risk of CVC-associated
      BSI in patients cared for by "float" nurses for more than 60% of the duration of
      the CVC. In multivariable analysis, risk factors for CVC-associated BSIs were the
      use of TPN in non-antimicrobial-impregnated CVCs (P = .0001), patient cared for
      by a float nurse for more than 60% of CVC-days (P = .0019), no antibiotics
      administered to the patient within 48 hours of insertion (P = .0001), and patient
      unarousable for 70% or more of the duration of the CVC (P = .0001). Peripherally
      inserted central catheters (PICCs) were associated with a lower risk for CVC
      associated BSI (P = .0001). CONCLUSIONS: Antimicrobial-impregnated CVCs reduced
      the risk of CVC-associated BSI by 66% in patients receiving TPN. Limiting the use
      of float nurses for ICU patients with CVCs and the use of PICCs may also reduce
      the risk of CVC-associated BSI.

PMID- 14700408
TI  - Preventing central venous catheter-associated primary bloodstream infections:
      characteristics of practices among hospitals participating in the Evaluation of
      Processes and Indicators in Infection Control (EPIC) study.
AB  - OBJECTIVES: To describe the conceptual framework and methodology of the
      Evaluation of Processes and Indicators in Infection Control (EPIC) study and
      present results of CVC insertion characteristics and organizational practices for
      preventing BSIs. The goal of the EPIC study was to evaluate relationships among
      processes of care, organizational characteristics, and the outcome of BSI.
      DESIGN: This was a multicenter prospective observational study of variation in
      hospital practices related to preventing CVC-associated BSIs. Process of care
      information (eg, barrier use during insertions and experience of the inserting
      practitioner) was collected for a random sample of approximately 5 CVC insertions
      per month per hospital during November 1998 to December 1999. Organization
      demographic and practice information (eg, surveillance activities and staff and
      ICU nurse staffing levels) was also collected. SETTING: Medical, surgical, or
      medical-surgical ICUs from 55 hospitals (41 U.S. and 14 international sites).
      PARTICIPANTS: Process information was obtained for 3,320 CVC insertions with an
      average of 58.2 (+/- 16.1) insertions per hospital. Fifty-four hospitals provided
      policy and practice information. RESULTS: Staff spent an average of 13 hours per
      week in study ICU surveillance. Most patients received nontunneled, multiple
      lumen CVCs, of which fewer than 25% were coated with antimicrobial material.
      Regarding barriers, most clinicians wore masks (81.5%) and gowns (76.8%); 58.1%
      used large drapes. Few hospitals (18.1%) used an intravenous team to manage ICU
      CVCs. CONCLUSIONS: Substantial variation exists in CVC insertion practice and BSI
      prevention activities. Understanding which practices have the greatest impact on
      BSI rates can help hospitals better target improvement interventions.

PMID- 14700409
TI  - Bloodstream infections in a community hospital: a 25-year follow-up.
AB  - OBJECTIVE: To examine the current status of bloodstream infections (BSIs) in a
      community hospital as part of a 25-year longitudinal study. DESIGN: Retrospective
      descriptive epidemiologic study. SETTING: Community teaching hospital. PATIENTS:
      All inpatients in 1998 with a positive blood culture who met the CDC NNIS System
      case definition of BSI. METHODS: Cases were stratified by underlying illness
      category using case mix adjustment categories (after McCabe) and reviewed for
      associations among mortality, underlying illness severity, and multiple clinical
      and laboratory parameters. RESULTS: Of 19,289 patients discharged in 1998, 185
      had an episode of infection documented by blood culture (96 cases per 10,000
      inpatients). BSI was twice as frequent in patients 65 years and older compared
      with younger patients. BSIs caused or contributed to the deaths of 22 patients
      for an overall case-fatality rate of 11.9% compared with 20.7% in 1982 (P = .02).
      Striking decreases were noted for in-hospital patient mortality in 1998 for BSIs
      with ultimately and rapidly fatal underlying illnesses (P = .02 and P < .10,
      respectively). Primary bacteremia decreased compared with 1982. Antibiotic use
      was vigorous, but resistance was modest in both nosocomial and community-acquired
      organisms and had changed little from 1982 and 1987. CONCLUSIONS: Compared with
      previous studies, case-fatality rates in patients with BSI were substantially
      lower in rapidly fatal and ultimately fatal underlying illness categories.
      Antibiotic use was extensive but prompt and appropriate. Microorganism resistance
      to antibiotics changed little from the 1980s.

PMID- 14700410
TI  - Prevalence of the use of central venous access devices within and outside of the
      intensive care unit: results of a survey among hospitals in the prevention
      epicenter program of the Centers for Disease Control and Prevention.
AB  - OBJECTIVE: To determine the prevalence of central venous catheter (CVC) use among
      patients both within and outside the ICU setting. DESIGN: A 1-day prevalence
      survey of CVC use among adult inpatients at six medical centers participating in
      the Prevention Epicenter Program of the CDC. Using a standardized form, observers
      at each Epicenter performed a hospital-wide survey, collecting data on CVC use.
      SETTING: Inpatient wards and ICUs of six large urban teaching hospitals. RESULTS:
      At the six medical centers, 2,459 patients were surveyed; 29% had CVCs. Among the
      hospitals, from 43% to 80% (mean, 59.3%) of ICU patients and from 7% to 39%
      (mean, 23.7%) of non-ICU patients had CVCs. Despite the lower rate of CVC use on
      non-ICU wards, the actual number of CVCs outside the ICUs exceeded that of the
      ICUs. Most catheters were inserted in the subclavian (55%) or jugular (22%) site,
      with femoral (6%) and peripheral (15%) sites less commonly used. The jugular
      (33.0% vs 16.6%; P < .001) and femoral (13.8% vs 2.7%; P < .001) sites were more
      frequently used in ICU patients, whereas peripherally inserted (19.9% vs 5.9%; P
      < .001) and subclavian (60.7% vs 47.3%; P < .001) catheters were more commonly
      used in non-ICU patients. CONCLUSIONS: Current surveillance and infection control
      efforts to reduce morbidity and mortality associated with bloodstream infections
      concentrate on the high-risk ICU patients with CVCs. Our survey demonstrated that
      two-thirds of identified CVCs were not in ICU patients and suggests that more
      efforts should be directed to patients with CVCs who are outside the ICU.

PMID- 14700411
TI  - Administrative databases provide inaccurate data for surveillance of long-term
      central venous catheter-associated infections.
AB  - BACKGROUND: Efficient methods are needed to monitor infections associated with
      long-term central venous catheters (CVCs) in both inpatient and outpatient
      settings. Automated medical records and claims data have been used for
      surveillance of these infections without evaluation of their accuracy or
      validity. OBJECTIVE: To determine the feasibility of using electronic records to
      identify CVC placement and design a system for identifying CVC-associated
      infections. DESIGN AND SETTING: Retrospective cohort study at an HMO and two
      teaching hospitals in Boston, one adult (hospital A) and one pediatric (hospital
      B), between January 1991 and December 1997. Tunneled catheters, totally implanted
      catheters, and hemodialysis catheters were examined. Claims databases of both the
      HMO and the hospitals were searched for 10 CPT codes, 2 ICD-9 codes, and internal
      charge codes indicating CVC insertion. Lists were compared with each other and
      with medical records for correlation and accuracy. PATIENTS: All members of the
      HMO who had a CVC inserted at one of the two hospitals during the study period.
      RESULTS: There was wide variation in the CVC insertions identified in each
      database. Although ICD-9 codes at each hospital and CPT/ICD-9 combinations at the
      HMO found similar total numbers of CVCs, there was little overlap between the
      individuals identified (62% for hospital A with HMO and 4% for hospital B).
      CONCLUSION: Claims data from different sources do not identify the same CVC
      insertion procedures. Current administrative databases are not ready to be used
      for electronic surveillance of CVC-associated complications without extensive
      modification and validation.

PMID- 14700412
TI  - Electronic interpretation of chest radiograph reports to detect central venous
      catheters.
AB  - OBJECTIVE: To evaluate whether a natural language processing system, SymText, was
      comparable to human interpretation of chest radiograph reports for identifying
      the mention of a central venous catheter (CVC), and whether use of SymText could
      detect patients who had a CVC. DESIGN: To identify patients who had a CVC, we
      performed two surveys of hospitalized patients. Then, we obtained available
      reports from 104 patients who had a CVC during one of two cross-sectional surveys
      (ie, case-patients) and 104 randomly selected patients who did not have a CVC
      (ie, control-patients). SETTING: A 600-bed public teaching hospital. RESULTS:
      Chest radiograph reports were available from 124 of the 208 participants.
      Compared with human interpretation, SymText had a sensitivity of 95.8% and a
      specificity of 98.7%. The use of SymText to identify case- and control-patients
      resulted in a sensitivity of 43% and a specificity of 98%. Successful application
      of SymText varied significantly by venous insertion site (eg, a sensitivity of
      78% for subclavian and a sensitivity of 3.7% for femoral). Twenty-six percent of
      the case-patients had a femoral CVC. CONCLUSIONS: Compared with human
      interpretation, SymText performed well in interpreting whether a report mentioned
      a CVC. In patient populations with less frequent CVC placement in femoral veins,
      the sensitivity for CVC detection likely would be higher. Applying a natural
      language processing system to chest radiograph reports may be a useful adjunct to
      other data sources to automate detection of patients who had a CVC.

PMID- 14700413
TI  - Improving water quality can reduce pyrogenic reactions associated with reuse of
      cardiac catheters.
AB  - OBJECTIVE: To report the results of our preintervention investigation and
      subsequent 19-month three-phase intervention study designed to reduce pyrogenic
      reactions among patients undergoing cardiac catheterization using reprocessed
      catheters. DESIGN: A case-control study for the preintervention period and a
      prospective cohort study for the intervention period. SETTING: A 400-bed hospital
      in Belo Horizonte, Brazil. PARTICIPANTS: Any patient undergoing cardiac
      catheterization in the hospital. INTERVENTIONS: Three intervention phases were
      implemented to improve the quality of the water supplied to the cardiac catheter
      reprocessing laboratory. Standard operating procedures for reprocessing cardiac
      catheters were established and reprocessing staff were trained and educated.
      RESULTS: The rate of pyrogenic reactions decreased significantly during the
      intervention phases, from 12.8% (159 of 1,239) in phase 1 to 5.3% (38 of 712) in
      phase 2 to 0.5% (4 of 769) in phase 3 (chi-square test for linear trend, 97.5; P
      < .001). CONCLUSION: Improving water quality and using standard operating
      procedures for reprocessing catheters can prevent pyrogenic reactions in
      hospitalized patients.

PMID- 14700414
TI  - Clinical experience with minocycline and rifampin-impregnated central venous
      catheters in bone marrow transplantation recipients: efficacy and low risk of
      developing staphylococcal resistance.
AB  - In this retrospective evaluation of the 4-year clinical use of minocycline and
      rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we
      report low risk of development of staphylococcal resistance to the antibiotics
      coating the catheters and efficacy in preventing primary staphylococcal
      bloodstream infections.

PMID- 14700415
TI  - Roseomonas infection associated with a left ventricular assist device.
AB  - Roseomonas species have been increasingly noted as causes of human infection. We
      present what we believe is the first case of left ventricular assist device
      (LVAD) infection secondary to Roseomonas. The clinical characteristics of
      Roseomonas infection and the pertinent features of LVAD infection are reviewed.

PMID- 14700416
TI  - Ignorance in developmental and behavioural disorders.

PMID- 14700417
TI  - Biostatistics 102: quantitative data--parametric & non-parametric tests.

PMID- 14700418
TI  - General practitioners' knowledge on childhood developmental and behavioural
      disorders.
AB  - INTRODUCTION: Childhood developmental and behavioural disorders are increasingly
      being recognised, with high demands for earlier diagnosis and intervention. In
      Singapore, referrals to the Child Development Unit, KK Women's and Children's
      Hospital, originate mainly from primary health care practitioners, who therefore
      should have adequate baseline knowledge of normal development as well as common
      developmental and behavioural disorders. METHODOLOGY: A pilot study, using a
      questionnaire survey, was conducted, with the aim of assessing existing knowledge
      in childhood developmental and behavioural paediatrics amongst a cohort of
      general practitioners (GPs) in Singapore. True/False questions on normal
      development as well as developmental disorders such as autistic spectrum disorder
      (ASD), attention deficit/hyperactivity disorder (ADHD) and learning disability,
      were structured. These disorders were selected because of their relatively higher
      prevalence. RESULTS: A total of 48 GPs were surveyed, representing 2% of non
      specialists practising in the private sector. The median total score (T-score)
      was 9 (range 6 to 13) of a possible 14. Only just over a-third of the group
      achieved the pass rate (defined arbitrarily as 75%) for T-score, with two-thirds
      replying correctly to all questions on normal development. Scores for factual
      ASD/ADHD questions were also not ideal, with some myths being believed as truths.
      CONCLUSION: The scores reflect knowledge and educational deficits in
      developmental paediatric medicine amongst the study cohort. Expected to provide
      holistic care and counselling, these GPs are currently insufficiently equipped
      with the necessary knowledge and skills to support families of special-needs
      children. Education and training programmes in this aspect of paediatric medicine
      are clearly needed, through the organisation of CME lectures and incorporation of
      various developmental topics into the training curriculum. This will enable early
      identification and diagnosis of childhood developmental and behavioural
      disorders, which will in turn allow greater optimisation of potential and
      functionality in these special-needs children.

PMID- 14700419
TI  - Open reduction and internal fixation of fractures of the acetabulum--local
      experience.
AB  - INTRODUCTION: It is now widely accepted that open reduction and internal fixation
      of displaced acetabular fractures should be the standard of care. This paper
      reports a case series of acetabular fracture fixation performed at the Changi
      General Hospital by a single trauma surgeon. PATIENTS AND METHODS: A
      retrospective study was conducted of 15 consecutive cases of displaced acetabular
      fracture fixation between February 1996 and September 1999. Outcome was assessed
      radiologically and functionally with the use of a hip scoring system used by
      Matta. RESULTS: The patients' age had a mean of 34.9 years. All fractures were a
      result of high energy trauma. The median duration to operation upon admission was
      eight days. The mean hospital stay was 24.9 days and the mean medical
      hospitalisation leave was 159 days. Bony union was achieved in all patients. Two
      patients (13.3%) had a residual displacement of 1 mm. Four patients (26.6%) had a
      residual displacement of 2 mm. Of these four patients with 2 mm displacement, two
      eventually developed osteoarthritis. Subsequently, one of the two with OA
      required revision to a total hip arthroplasty two years post fracture. Other
      complications include 1 (6%) wound infection and 2 (13%) deep vein thrombosis.
      There were no complications of heterotopic ossification or sciatic nerve injury.
      Functional scores with a minimum follow up of one year and a mean of 22.6 months
      follow-up were excellent in 13.3%, good in 66.7%, fair in 13.3% and poor in 6.7%.
      CONCLUSION: The number of cases in this paper is insufficient to produce any
      statisticallly significant outcome predictors but accuracy of reduction is an
      important factor. A good to excellent result was attained in 80% of the patients
      which confirms that open reduction and internal fixation is the treatment of
      choice for displaced and acetabular fractures.

PMID- 14700420
TI  - Concurrent chemoradiotherapy with daily low dose intra-arterial cisplatin plus 5
      fluorouracil for stage IV nasopharyngeal cancer.
AB  - This study aims to treat locally-advanced nasopharyngeal cancer by concurrent
      conventional irradiation at 2.0 Gy/day five days per week up to a total dose of
      68 Gy, and daily intra-arterial infusion of cisplatin 3 mg/m2 plus 24 hours
      intravenous drip infusion of 5-fluorouracil 150 mg/m2 per day, five days per
      week. All of five enrolled patients completed the schedule, and treatment
      compliance was considered to be identical. Of the five patients evaluable for
      response, four with complete response (80%) and one with partial response (20%),
      with an overall response rate of 100% was achieved. The median survival time was
      26 months. Two-year survival of the patients was 80%. This regimen showed
      marginal mucositis but well tolerated. We concluded that this treatment option is
      safe and effective for the locally-advanced nasopharyngeal cancer.

PMID- 14700421
TI  - Acute myocardial infarction in the elderly--the differences compared with the
      young.
AB  - OBJECTIVES: The aim of the study was to determine the differences in
      presentation, complications, management and outcome of elderly patients with
      acute myocardial infarction (AMI) compared to young patients. MATERIALS AND
      METHODS: All case-notes with a discharge or death diagnosis ofAMI between January
      and July 1999 at a restructured hospital in Singapore were reviewed
      retropectively. Patients were categorised into those younger than 65 years
      (young) and those 65 years or older (elderly). Data on the demographic and
      clinical profile of patients were collected. RESULTS: There were 112 young and
      101 elderly AMI patients. Chest pain was the most common presentation in both age
      groups, but more likely in the young than the elderly (89.3% vs 66.3%; p <
      0.001). Atypical presentations were more likely in the elderly, with shortness of
      breath as the most common presentation (20.8% vs 5.4%; p < 0.001). The elderly
      were more likely to have complications of cardiac failure (65.3% vs 25%; p <
      0.001) and cardiogenic shock (8.9% vs 0.9%; p = 0.006). The elderly were less
      likely to receive thrombolytic therapy (35.8% vs 64.8%; p < 0.001) as they were
      more likely to have contraindications (34.5% vs 6.8%; p = 0.002). The elderly
      were also less likely to receive beta-blockers (21.8% vs 60.7%; p < 0.001). In
      hospital mortality was higher in the elderly (20.8% vs 2.7%; p < 0.001).
      Cardiogenic shock complicating AMI was associated with high in-hospital
      mortality. CONCLUSION: In AMI patients, chest pain was the most common
      presentation in both age groups, though less frequently in the elderly. Atypical
      presentations were more likely in the elderly, with shortness of breath as the
      most common atypical presentation. In elderly AMI patients, prevalence of cardiac
      failure was higher, use of beta-blockers was lower and in-hospital mortality was
      higher than young patients.

PMID- 14700422
TI  - SARS--lessons from two Singapore General Hospital cases.
AB  - Two cases of Severe Acute Respiratory Syndrome (SARS) that occurred in Singapore
      General Hospital are described. The lessons learnt are outlined.

PMID- 14700423
TI  - Ulcerative colitis and motor neurone disease: causal or coincidental?
AB  - Neurological involvement associated with inflammatory bowel disease is well
      established though rarely reported in the literature. The coexistence of motor
      neurone disease with ulcerative colitis has never been previously documented. The
      case of a 53-year-old Indian male with distal ulcerative colitis who, two and a
      half years later, developed dysarthria, dysphagia, a wasted fasciculating tongue
      and palatal palsy characteristic of bulbar type motor neurone disease is
      described. Topical and oral steroids together with azathioprine and mesalazine
      suppositories controlled the bowel symptoms but did not improve the neurological
      deficit. Subsequently, the antiglutamate agent riluzole improved the mobility of
      his tongue. The close temporal relationship and relative infrequency of both
      these conditions in a Malaysian population along with the recognised association
      between ulcerative colitis and other neurological conditions deserve careful
      consideration as to whether a common denominator is involved. Documentation of
      coexistence of both disorders in a single patient is important in case similar
      associations are reported in future.

PMID- 14700424
TI  - Psychosis--a need for preemptive intervention?
AB  - With the advent of newer antipsychotic medications with fewer side-effects both
      clinicians and patients may be more willing to take early preemptive measures in
      treating psychotic disorders. We present a case report of use of
      pharmacotherapeutic intervention in an individual with either possible prodromal
      symptoms of schizophrenia or a subthreshold disorder. This case presented to us
      with the ethical dilemma inherent in treating a patient with subthreshold
      disorder. The options were either watchful waiting or preemptive treatment. In
      this case the patient was very distressed by his symptoms and had requested
      treatment with medications. Indeed, treatment has resulted in the remission of
      his symptoms and restored him to his previous level of functioning.

PMID- 14700425
TI  - Who are the residents of a nursing home in Singapore? (SMJ Vol 44 Issue 2
      February 2003).

PMID- 14700426
TI  - The SARS outbreak: how many reminders do we need? (SMJ Vol 44 Issue 3 April
      2003).

PMID- 14700427
TI  - Randomised controlled trials (RCTs)--sample size: the magic number (SMJ Vol 44
      Issue 4 April 2003).

PMID- 14700428
TI  - Clinics in diagnostic imaging (88). Gynaecomastia of the right breast and
      carcinoma of the left breast.
AB  - An 83-year-old man presented with a painless lump in his left breast for one
      year. Mammograms showed an ill-defined uncalcified high-density subareolar mass
      in the left breast and minimal fibroglandular density radiating beneath the
      nipple into the fatty tissue of the right breast. US showed an irregular,
      heterogeneously-hypoechoic mass with mild posterior transmission. The
      differential diagnosis of breast enlargement in men is discussed. Mammographical
      and US features of gynaecomastia and male breast carcinoma are presented.

PMID- 14700429
TI  - Goldenrod.

PMID- 14700430
TI  - A jump start on allergen avoidance for expectant parents.

PMID- 14700431
TI  - Lessons learned from latex allergy.

PMID- 14700432
TI  - Cockroach allergen abatement in inner-city homes.

PMID- 14700433
TI  - Response to "effect of anti-IgE therapy in patients with food allergy".

PMID- 14700434
TI  - Usefulness of specific IgE antibody tests: a progress report.
AB  - LEARNING OBJECTIVES: To enable the readers to recognize some of the history,
      problems, progress, interpretation, and present status of assays for specific IgE
      (s-IgE) antibodies. DATA SOURCES: Peer-reviewed literature in the field. STUDY
      SELECTION: Key articles were selected by the author. RESULTS: Clinical and
      analytical studies have differed widely in their conclusions as to the
      performance of tests for s-IgE. Study conclusions depend on the testing method
      used, the allergen(s) studied, patient selection, and, most importantly, the
      standards used for comparison. Today, only a handful of the once commercially
      developed assays still exist, and some of these still do not compare well to an
      analytical ideal standard. However, with the extent of regulation and economic
      pressures, most of the surviving s-IgE tests are considerably improved over what
      had existed before them. CONCLUSIONS: Allergic diseases with multiple symptom
      patterns seem to be increasing in modern societies. Objective methods are needed
      to differentiate allergic origins from other mechanisms that cause similar
      symptoms. Accurate, quantitative, and objective methods for s-IgE measurement are
      now available and can be used effectively in clarifying allergic diagnoses when
      interpreted in conjunction with the clinical history.

PMID- 14700435
TI  - Recurrent cough and normal sweat chloride test.

PMID- 14700436
TI  - Environmental exposure reduction in high-risk newborns: where do we start?
AB  - BACKGROUND: When analyzing the effect of environmental exposure reduction
      measures on asthma in high-risk children, one must know how far asthmatic
      families already have applied such measures, because this would affect the
      effectiveness and efficiency of interventions aimed at reducing environmental
      exposure. OBJECTIVE: To describe the room for improvement by asthmatic families
      in mite, pet, and food allergen reducing measures and in parental passive smoking
      and to determine the resulting levels of mite and pet allergens by the applied
      sanitation measures. METHODS: Data were sampled by observation, weekly diary
      entries, and questionnaire when the infant was 6 months old and 1 year old. Dust
      samples were collected by vacuuming the living room floor and the parental and
      infant mattresses. Multiple logistic regression analyses were applied with the
      use of mattress encasing, having a smooth floor covering, having pets, exclusive
      breast-feeding and/or hypoallergenic formula during the infant's first 6 months,
      and passive smoking as the dependent variables. RESULTS: Frequencies of applied
      measures were as follows: having a smooth floor covering, 36%; daily house
      cleaning, 27%; use of parental and infant antimite mattress encasings, 13% and
      9%, respectively; keeping no pets, 66%; no cow's milk-based regular formula, 13%;
      no solid foods in the first 6 months of life, 28%; and abstinence of smoking by
      the mother prenatally, 89%; by the mother postnatally, 85%; and by her partner,
      76%. Having a smooth floor covering and daily cleaning but not use of antimite
      mattress encasings resulted in significantly lower mite and pet allergen levels.
      CONCLUSIONS: There is (still) enough room for improvement to reduce exposure to
      inhalant and food allergens, especially by application of mattress encasings,
      exclusive breast-feeding and/or hypoallergenic formula feeding, and postponing
      the time until first solids are given.

PMID- 14700437
TI  - Latex hypersensitivity in Department of Veterans Affairs health care workers:
      glove use, symptoms, and sensitization.
AB  - BACKGROUND: This report of the prevalence of latex glove allergy in 3 Department
      of Veterans Affairs (VA) medical centers was a collaboration of the VA, the
      Centers for Disease Control and Prevention, and the National Institute for
      Occupational Safety and Health. OBJECTIVE: To enroll and evaluate personnel from
      across the entire hospital workforce for latex hypersensitivity and to determine
      the type and extent of latex glove use. METHODS: A questionnaire was administered
      that covered demographics, job category, latex glove use, and current latex glove
      allergic symptoms. Skin testing to aeroallergens was performed to evaluate the
      presence of atopy. Blood was drawn for analyses of serum antilatex IgE antibody
      by CAP assay. RESULTS: Of 1,959 subjects, 158 (8.1%) had latex glove-allergic
      symptoms, a positive latex CAP assay result, or both. In 1,003 subjects who
      reported latex glove use, 915 (91.4%) used nonpowdered gloves. A total of 133
      subjects reported latex glove allergic symptoms, and 36 subjects had positive CAP
      assay results. Latex sensitization was correlated with atopy, race, and latex
      glove exposure. Latex symptoms were correlated with atopy, a positive CAP assay
      result, and latex glove exposure. Of the 133 subjects with latex glove allergic
      symptoms, only 11 had positive CAP assay results, giving a prevalence of
      confirmed latex glove allergy of 0.6%. CONCLUSIONS: Symptoms attributed to latex
      gloves and/or latex sensitization occurred in 8.1% of the employee population,
      with exposure, race, and atopy being the major risk factors. Few symptomatic
      individuals were sensitized to latex (0.6%). This low rate of confirmed latex
      glove allergy may have been related to nonpowdered glove use.

PMID- 14700438
TI  - Cockroach counts and house dust allergen concentrations after professional
      cockroach control and cleaning.
AB  - BACKGROUND: It is known that cockroach allergen exposure is both frequent in
      inner-city homes and associated with asthma severity in children living in those
      homes. However, there have been few studies of interventions to reduce exposures
      in this setting. OBJECTIVE: To evaluate the effect of short-term professional
      cockroach control and intensive cleaning on allergen concentrations. METHODS:
      Families of children from a school-based asthma treatment program who had skin
      test results positive to cockroach allergen were enrolled if the home had
      cockroaches. Forty-nine homes were randomly assigned to receive professional
      cleaning with bait traps containing insecticide, professional cleaning with bait
      traps without insecticide, or no cleaning or bait traps. In all homes, dust was
      collected repeatedly to evaluate cockroach allergen Bla g 2 in the kitchen and
      bedroom, and cockroaches were trapped and counted repeatedly for more than 11
      weeks. RESULTS: Median cockroach counts were reduced in the homes treated with
      insecticide bait traps but not in other groups. There were significant reductions
      in allergen concentration in the kitchen in homes that received professional
      cleaning and had higher initial cockroach counts (54), regardless of whether bait
      traps had insecticide or not. CONCLUSIONS: We conclude that intensive cleaning
      can produce significant reductions in cockroach allergen in homes with heavy
      initial cockroach infestations.

PMID- 14700439
TI  - The relationship of sex to asthma prevalence, health care utilization, and
      medications in a large managed care organization.
AB  - BACKGROUND: Age-related sex differences in asthma hospitalizations and emergency
      department (ED) visits have been reported, but relationships of these differences
      to disease prevalence and outpatient management have not been defined. OBJECTIVE:
      To define the relationships of sex to asthma-related health care utilization and
      medications, accounting for age-related differences in asthma prevalence.
      METHODS: Computerized data from Southern California Kaiser-Permanente were used
      to identify asthmatic patients, aged 2 to 64 years, enrolled continuously during
      1999 and 2000. Age-specific asthma prevalence in 1999 was calculated to identify
      ages of male or female predominance. Males and females were compared with regard
      to asthma-related health care utilization outcomes (outpatient clinic visits, ED
      visits, and hospitalizations) and medication use (beta-agonists, inhaled
      steroids, and oral steroids). Hospitalizations, ED visits, and oral steroid use
      were considered markers of disease severity. RESULTS: Of the 60,694 subjects, the
      female-male prevalence ratio was approximately 35:65 at each age between 2 and 13
      years, it was inverse (65:35) between the ages of 23 and 64 years, and
      prevalences were relatively similar at the ages of 14 to 22 years. In patients
      aged 2 to 13 years, most utilization and medication variables were significantly
      greater in males (P < .01). Females aged 14 to 22 years had more outpatient and
      ED visits and used more oral steroids than males. In patients aged 23 to 64
      years, all utilization variables were significantly greater in females, except
      beta-agonist use and mean inhaled steroid dispensings. CONCLUSIONS: Asthma
      utilization and severity appear greater in males aged 2 to 13 years, somewhat
      greater in females aged 14 to 22 years, and definitely greater in females aged 23
      to 64 years. The mechanisms for these striking sex differences merit further
      investigation.

PMID- 14700440
TI  - Comparison of house dust mites found on different mattress surfaces.
AB  - BACKGROUND: House dust mites have been considered the most important source of
      allergens for humans. These allergens have been encountered at different indoor
      sites, mainly on mattresses and pillows. OBJECTIVE: To evaluate the number and
      different specimens of mites on Brazilian bunk-bed mattresses. METHODS: Dust
      samples were collected once using a standardized method on the upper mattress
      surface (US) and lower mattress surface (LS) (bed frame also included in the
      latter) of 58 mattresses. RESULTS: The total number of mite bodies on the LS was
      3.5-fold higher than on the US, with a mean concentration of 932 mites per gram
      of fine dust (mites/g) on the US (range, 0-3,375 mites/g) and 3,254 mites/g on
      the LS (range, 125-14,500 mites/g) (P < .001). Additionally, the number of house
      dust mite bodies on the LS was 2.4 higher than on the US (P < .001); the mean
      concentration was 750 mites/g on the US (range, 0-2,875 mites/g) and 1,816
      mites/g on the LS (range, 0-10,875 mites/g). Approximately 91% (n = 52) of the US
      and all LS dust samples had more than the limit of 100 mites/g. The most frequent
      family was Pyroglyphidae in both mattress surfaces, with Dermatophagoides
      pteronyssinus the most important species found. Storage mites, including
      Glycyphagidae (P < .001), Acaridae (P < .001), and other families (P < .001),
      also showed significant differences in the number of mites between both sample
      counts. CONCLUSIONS: This study shows a significant difference in US and LS mite
      counts, with higher counts on the LS. Mite allergen avoidance should include the
      LS and bed frame as potential targets.

PMID- 14700441
TI  - Topical pimecrolimus in the treatment of human allergic contact dermatitis.
AB  - BACKGROUND: Contact dermatitis is a common clinical problem, with prevalent
      sensitizers being cosmetics, metals, medicines, and plants. Plants of the
      Toxicodendron species cause allergic contact dermatitis (ACD) in 50% to 70% of
      the population. Pimecrolimus is an ascomycin macrolactam developed for the
      treatment of inflammatory skin diseases and approved by the US Food and Drug
      Administration for atopic dermatitis. There are studies supporting the
      effectiveness of macrolactams when administered before antigen challenge, but
      there are no studies describing the effectiveness of these drugs in the treatment
      of established human ACD. OBJECTIVE: To investigate the effect of topical
      pimecrolimus in the treatment of Toxicodendron-induced ACD once rash is evident.
      METHODS: Poison ivy tincture was applied to the bilateral anterior forearms of 12
      subjects with Finn Chambers (Allerderm Diagnostic Products, Petaluma, CA). After
      dermatitis was evident, volunteers treated each arm twice daily with either 1%
      topical pimecrolimus cream or placebo in a blinded fashion. Outcomes measured
      were a dermatitis grading score and time to rash and itch resolution. RESULTS:
      The median +/- SEM time for rash resolution was 16.55 +/- 1.59 days in the
      treatment group and 16.27 +/- 1.82 days in the placebo group (P = 0.601). The
      median time for itch resolution was 4.73 +/- 1.56 days in the treatment group and
      4.91 +/- 1.59 days in the placebo group (P = 0.167). The average dermatitis score
      was 2.26 +/- 0.17 in the treatment group and 2.32 +/- 0.15 in the placebo group
      (P = 0.62). CONCLUSIONS: The application of topical pimecrolimus is ineffective
      in the treatment of ongoing Toxicodendron-induced ACD.

PMID- 14700442
TI  - Regulation of CD23 in the chronic inflammatory response in asthma: a role for
      interferon-gamma and heat shock protein 70 in the TH2 environment.
AB  - BACKGROUND: Monocytic cells and alveolar macrophages (AMs) are activated in
      patients with asthma, producing inflammatory cytokines. This occurs despite a TH2
      environment that consists of the cytokines interleukin (IL) 4, IL-10, and IL-13.
      The mechanism by which this occurs may involve cross-linking of the low
      alphaffinity IgE receptor CD23. OBJECTIVE: To determine the effect of the TH2
      environment with interferon-gamma (IFN-gamma) and heat shock protein 70 (HSP 70)
      on CD23 receptor expression and tumor necrosis factor alpha (TNF-alpha)
      production. METHODS: We examined the effect of IL-4 and IL-13 in culture with IFN
      gamma and HSP 70 on CD23 expression in both THP-1 cells and AMs from healthy
      controls via flow cytometry. AMs from mild asthmatic patients and THP-1 cells
      were evaluated for TNF-alpha production after cross-linking CD23 with immune
      complexes. RESULTS: Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- +/-
      1.9-fold increase in TNF-alpha protein. AMs from healthy controls increased the
      geometric mean +/- SD of CD23 2.00- +/- 0.50-fold in IL-4 and 2.14- +/- 0.50-fold
      in IL-13. THP-1 cells cultured with IL-4 and IL-13 then stimulated with IFN-gamma
      or HSP 70 increased CD23 expression above baseline as follows: IL-4, 2.16- +/-
      0.31-fold; IL-13, 2.66- +/- 0.43-fold; IFN-gamma, 2.03- +/- 0.34-fold; IL-4/IFN
      gamma, 9.14- to 4.02-fold; IL-13/IFN-gamma, 11.51- +/- 5.51-fold; IL-4/HSP, 5.20-
      +/- 0.61-fold; and IL-13/HSP, 5.60- +/- 0.79-fold. Stimulating the CD23 receptor
      with immune complexes significantly increased TNF-alpha production by THP-1 cells
      stimulated with IFN-gamma, IL-4, IL-13, or a combination of these. CONCLUSIONS:
      Both IFN-gamma and HSP 70, in the TH2 environment, up-regulate CD23 expression
      and thus may play an important role in maintaining the chronic inflammatory state
      in asthma.

PMID- 14700443
TI  - Psychogenic intractable sneezing: case reports and a review of treatment options.
AB  - OBJECTIVE: To report 2 cases of the uncommonly seen diagnosis of psychogenic
      intractable sneezing, to review the clinical presentation, workup, and various
      previous treatment modalities, and to present a unique method of treatment. DATA
      SOURCES: The literature was reviewed using a MEDLINE search of the following
      keywords: psychogenic intractable sneezing, paroxysmal sneezing, factitious
      sneezing, respiratory disorders, conversion disorders, habit cough, and
      psychogenic cough. The search was restricted to articles published from 1966
      onward, although older references were cross-referenced from more recent
      articles. RESULTS: Sneezing alone can be caused by foreign substances, odors,
      chemical irritants, allergies, and other less common factors. Psychogenic
      intractable sneezing, although not a particularly common disease, occurs mainly
      in adolescent girls for which a cause may not be found. Patients are usually
      refractory to various medications and have an otherwise unremarkable extensive
      workup. Treatments have included corticosteroids, antihistamines, hydroxyzine
      hydrochloride, and decongestants among other pharmacologic agents, as well as
      psychotherapy. Based on the presented case reports, a trial of isotonic sodium
      chloride solution with suggestion therapy was able to rid the patients of their
      intractable sneezing. CONCLUSIONS: Psychogenic intractable sneezing is a real
      disease. Although other diseases may be considered, the workup may merely include
      an extensive history and physical examination. Many treatments have been tried
      with varying success, including those that incorporate psychotherapy. A variation
      of suggestiontherapy is offered as a unique treatment modality.

PMID- 14700444
TI  - Psyllium-associated anaphylaxis and death: a case report and review of the
      literature.
AB  - BACKGROUND: Psyllium use has increased significantly in the United States in part
      due to its lipid-lowering property. The increased prevalence of consumption has
      led to its recognition as an emerging food allergen. OBJECTIVES: To report the
      case of a 42-year-old woman who experienced fatal anaphylaxis after ingesting a
      psyllium-based product and to review the literature. METHODS: The MEDLINE
      database was searched for articles from 1966 to 2002 using the keywords psyllium
      or ispaghula and each of the following: allergy, hypersensitivity, anaphylaxis,
      and asthma. Both English and non-English articles were included. RESULTS:
      Psyllium hypersensitivity has been well described in health care workers and
      pharmaceutical plant employees. Clinical manifestations of allergy range from
      upper respiratory tract symptoms on inhalation to anaphylaxis on ingestion. The
      prevalence of sensitization varies between these 2 groups. The allergenic epitope
      is not known. CONCLUSIONS: We present a case of psyllium hypersensitivity that
      resulted in death. There is a clear association between atopy and psyllium
      allergy. The case underscores the fact that even nonprescription "natural"
      products can be harmful to people with allergies.

PMID- 14700445
TI  - Montelukast and fluticasone propionate.

PMID- 14700446
TI  - Levalbuterol.

PMID- 14700448
TI  - Achieving remission and managing relapse in depression.
AB  - Although antidepressants are effective, no more than one third of the depressed
      patients who begin treatment achieve full remission within 8 weeks of therapy.
      Remission, defined as virtually complete relief of symptoms and return to full
      functioning in all areas of life, should be thought of as the optimal goal for
      the initial phase of treatment of depression. This goal is recommended because
      residual symptoms (i.e., response without remission) are associated with a myriad
      of risks, including a higher rate of relapse. When compared with monotherapy,
      selective serotonin reuptake inhibitor (i.e., the current first-line standard of
      care) strategies may improve remission rates. These strategies include using
      maximally tolerated (i.e., higher than usual) doses of medication, switching to
      an antidepressant thought to have more than one mechanism of action, combining
      dissimilar medications (to presumably treat a broader range of symptoms), and
      using a combination of psychotherapy and medication. Ensuring that patients are
      indeed adherent with treatment is also worthwhile before assuming that a
      treatment has failed.

PMID- 14700447
TI  - Tolerability of cyclooxygenase 2 inhibitors and the advisability of oral
      challenge.

PMID- 14700449
TI  - Special issues related to the treatment of depression in women.
AB  - Depressive disorders in women are commonly associated with reproductive events.
      This association may be due in part to the changing balance between estrogen,
      progesterone, and other hormones that affect neurotransmitter function throughout
      a woman's lifecycle. Alternatively, they may be related to psychosocial events
      surrounding these pivotal times or to both sets of conditions. Some data suggest
      that depression in women tends to respond differently to antidepressant treatment
      than depression in men, underscoring the need to examine the risk and treatment
      of depressive disorders in males and females separately. Women have benefited
      considerably from serotonin reuptake inhibitor anti-depressants that are
      currently available. These agents appear to be more effective than the older
      tricyclic antidepressants in treating various depressive disorders that occur
      commonly or exclusively in women. Additionally, serotonin reuptake inhibitors
      have increased tolerability in women, who generally experience more adverse
      effects from tricyclics and monoamine oxidase inhibitors than do men. Estrogen
      appears to enhance antidepressant response in postmenopausal women receiving
      estrogen replacement therapy. More research is needed, however, that examines how
      the balance between estrogen, progesterone, and other hormones affects
      neurotransmitter function.

PMID- 14700451
TI  - Long-term side effects of SSRIs: sexual dysfunction and weight gain.
AB  - Selective serotonin reuptake inhibitors are associated with a variety of side
      effects, many of which are resolved during the first couple of weeks of
      treatment. Side effects that emerge or persist after 1 month of treatment include
      sexual dysfunction and weight gain. Although these adverse events are serious,
      they can be managed successfully if recognized early.

PMID- 14700450
TI  - Immediate-release versus controlled-release formulations: pharmacokinetics of
      newer antidepressants in relation to nausea.
AB  - Newer antidepressants are generally as efficacious as but often have fewer side
      effects than their predecessors such as the tricyclic antidepressants and
      monoamine oxidase inhibitors. These newer antidepressants include the selective
      serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, fluoxetine,
      fluvoxamine, paroxetine, and sertraline; venlafaxine, a serotonin-norepinephrine
      reuptake inhibitor; and bupropion, a selective norepinephrine and dopamine
      reuptake inhibitor. Most of these antidepressants have half-lives that enable
      them to be administered as infrequently as 1 to 3 times per day. To further
      improve upon the ease of use, controlled-release formulations of bupropion,
      fluoxetine, paroxetine, and venlafaxine have been manufactured. Potential
      pharmacokinetic advantages of these formulations include lower peak plasma drug
      concentrations and smaller fluctuations between peak and trough plasma drug
      concentrations, which might influence the tolerability of these medications.
      Tolerability advantages seen with some of these medications include diminished
      nausea. The 3 controlled-release agents that are designed to be taken daily-
      bupropion, paroxetine, and venlafaxine--are associated with lower incidences of
      nausea overall and nausea leading to treatment discontinuation than are their
      immediate-release formulations. However, the rates of nausea are similar with
      both formulations of fluoxetine, despite higher peak plasma drug concentrations
      and greater fluctuation between peak and trough plasma drug concentrations with
      fluoxetine weekly than with fluoxetine daily. Although the connection has not
      been proven, more stable pharmacokinetic profiles might be the cause for the low
      occurrence of nausea with some controlled-release newer antidepressants.

PMID- 14700452
TI  - Improving antidepressant adherence.
AB  - Frequently, patients suffering from depressive disorders discontinue
      antidepressant treatment due to the unpleasant side effects of these medications,
      particularly in the first month of therapy. Good tolerability (particularly in
      the early stages of treatment), patient education, and the quality of the
      relationship between physicians and patients are all common determining factors
      of patient adherence. Controlled-release antidepressant agents have the potential
      to improve tolerability early in the course of therapy, one of the most likely
      periods of dropout from treatment. Side effects for controlled-release
      formulations are often more favorable because controlled-release formulations
      exhibit lower peak plasma drug concentrations when compared with immediate
      release formulations. Venlafaxine extended-release (XR), bupropion sustained
      release (SR), and paroxetine controlled-release (CR) are 3 commonly utilized
      controlled-release antidepressants that have demonstrated improvement over their
      immediate-release predecessors in reducing certain adverse effects.

PMID- 14700453
TI  - Potential new drug delivery systems for antidepressants: an overview.
AB  - Oral administration is probably a nonoptimal delivery system for most
      psychotropics. Scientists are turning to optimizing drug delivery as a method for
      enhancing antidepressant response. Advances in oral drug delivery have come in
      the form of sustained-release formulations of antidepressants, which have
      smoothed the plasma drug concentration maxima and minima, thus decreasing side
      effects and increasing tolerability. The future of pharmacologic treatment for
      psychiatric disorders may be in part dependent on nonoral drug delivery systems
      such as implantable and transdermal delivery systems. Like the available
      sustained-release formulations of antidepressants, these alternative delivery
      systems will have enhanced safety, tolerability, and efficacy because of their
      ability to maintain a more constant circulating drug level. Implantable devices
      that sense, stimulate, deliver to, and record from biological systems are being
      developed through microtechnology and nanotechnology. Transdermal delivery
      techniques, such as passive diffusion, sonophoresis, electroporation, and
      iontophoresis, enhance the skin's permeability to drugs. Iontophoresis appears to
      be a promising and perhaps the most efficient assisted-delivery technique for
      future antidepressant transdermal delivery.

PMID- 14700454
TI  - Safety and insecurity: exploring the moderating effect of organizational safety
      climate.
AB  - This research reconciled disparate findings regarding the relationship between
      job insecurity and safety by examining organizational safety climate as a
      potential moderator. It was predicted that a strong organizational safety climate
      would attenuate the negative effects of job insecurity on self-reported safety
      outcomes such as safety knowledge, safety compliance, accidents, and injuries.
      Data collected from 136 manufacturing employees were consistent with these
      predictions. Results are discussed in light of escalating interest in how
      organizational factors can affect employee safety.

PMID- 14700455
TI  - A longitudinal study of employee adaptation to organizational change: the role of
      change-related information and change-related self-efficacy.
AB  - This study examined the role of information, efficacy, and 3 stressors in
      predicting adjustment to organizational change. Participants were 589 government
      employees undergoing an 18-month process of regionalization. To examine if the
      predictor variables had long-term effects on adjustment, the authors assessed
      psychological well-being, client engagement, and job satisfaction again at a 2
      year follow-up. At Time 1, there was evidence to suggest that information was
      indirectly related to psychological well-being, client engagement, and job
      satisfaction, via its positive relationship to efficacy. There also was evidence
      to suggest that efficacy was related to reduced stress appraisals, thereby
      heightening client engagement. Last, there was consistent support for the stress
      buffering role of Time 1 self-efficacy in the prediction of Time 2 job
      satisfaction.

PMID- 14700456
TI  - Gendered work conditions, health, and work outcomes.
AB  - This cross-sectional study of nonfaculty university employees examined
      associations among gendered work conditions (e.g., sexism and discrimination),
      job demands, and employee job satisfaction and health. Organizational
      responsiveness and social support were examined as effect modifiers. Comparisons
      were made by gender and by the male-female ratio in each job category. The
      relationship of gendered conditions of work to outcomes differed on the basis of
      respondents' sex and the job sex ratio. Although the same predictors were
      hypothesized for job satisfaction, physical health, and psychological distress,
      there were some differing results. The strongest correlate of job satisfaction
      was social support; perceived sexism in the workplace also contributed for both
      men and women. Organizational factors associated with psychological distress
      differed between female- and male-dominated jobs.

PMID- 14700457
TI  - The influence of prior commitment on the reactions of layoff survivors to
      organizational downsizing.
AB  - Nurses (N = 179; Study 1) and managers (N = 154; Study 2) participated in 2 panel
      studies examining the relationship among prior commitment (affective and
      continuance commitment and perceived organizational support), coping strategies,
      and survivors' attitudes and perceptions during and following downsizing. In
      Study 1, perceived organizational support was significantly positively related to
      control-oriented coping, job satisfaction, and intention to remain and negatively
      related to perceived job insecurity and burnout 2 years later. In Study 2, coping
      mediated the relationship between the prior commitment variables and job
      alienation, health symptoms, and burnout following the downsizing. Control
      oriented coping was associated with elevated levels of health symptoms and
      burnout following the downsizing, suggesting that control-oriented coping may
      have positive effects in the short term but potentially harmful effects in the
      long term.

PMID- 14700458
TI  - Customer-related social stressors and burnout.
AB  - Although almost all literature on burnout implicitly assumes that burnout is
      primarily caused by stressful employee-customer interactions, only a few studies
      have addressed this empirically. A principal-components analysis of a newly
      developed instrument assessing various forms of customer-related social stressors
      (CSS) in 3 different service jobs (N = 591) revealed 4 themes of CSS:
      disproportionate customer expectations, customer verbal aggression, disliked
      customers, and ambiguous customer expectations. These 4 CSS predict burnout
      beyond a variety of control variables. Contrary to other predictors of burnout
      analyzed in previous studies, the amount of variance explained in exhaustion
      (14%) by the 4 CSS scales is not higher than for personal accomplishment (14%)
      and is considerably lower than for depersonalization (23%).

PMID- 14700459
TI  - Expanding the psychosocial work environment: workplace norms and work-family
      conflict as correlates of stress and health.
AB  - This study examined the contributions of organizational level norms about work
      requirements and social relations, and work-family conflict, to job stress and
      subjective health symptoms, controlling for Karasek's job demand-control-support
      model of the psychosocial work environment, in a sample of 1,346 employees from
      56 firms in the Norwegian food and beverage industry. Hierarchical linear
      modeling analyses showed that organizational norms governing work performance and
      social relations, and work-to-family and family-to-work conflict, explained
      significant amounts of variance for job stress. The cross-level interaction
      between work performance norms and work-to-family conflict was also significantly
      related to job stress. Work-to-family conflict was significantly related to
      health symptoms, but family-to-work conflict and organizational norms were not.

PMID- 14700460
TI  - The emergence of cultural self-constructs: autobiographical memory and self
      description in European American and Chinese children.
AB  - This study examined the emergence of cultural self-constructs as reflected in
      children's remembered and conceptual aspects of the self. European American and
      Chinese children in preschool through 2nd grade participated (N=180). Children
      each recounted 4 autobiographical events and described themselves in response to
      open-ended questions. American children often provided elaborate and detailed
      memories focusing on their own roles, preferences, and feelings; they also
      frequently described themselves in terms of personal attributes, abstract
      dispositions, and inner traits in a positive light. Chinese children provided
      relatively skeletal accounts of past experiences that centered on social
      interactions and daily routines, and they often described themselves in terms of
      social roles, context-specific characteristics, and oven behaviors in a neutral
      or modest tone. Findings are discussed in light of the self as a constructed
      meaning system of culture that emerges early in life.

PMID- 14700461
TI  - The miniaturization of expression in the development of emotional self
      regulation.
AB  - This study tested an internalization model of emotional development proposing
      that emotional expression decreases during childhood in situations in which
      emotions serve only self-regulation. This model was tested by inducing joy and
      disappointment in solitary versus interpersonal conditions in 3 gender-matched,
      20-member groups of 6-, 7-, and 8-year-olds. Results supported the model:
      Expression--but not self-reported feeling--decreased in solitary conditions as a
      function of increasing age, whereas both expression and feeling remained stable
      in the interpersonal condition. This effect also correlated positively with the
      ability to discriminate between expression and feeling on a conceptual level.
      Results are discussed in relation to the major developmental trend toward
      creating a mental level of self-regulation--first described by Vygotsky.

PMID- 14700463
TI  - Children who question their heterosexuality.
AB  - Many gay, lesbian, and bisexual adults report a period of childhood sexual
      questioning--an uneasy questioning of their heterosexuality brought on by same
      sex attractions and motivating same-sex sexual exploration. This article
      evaluates hypotheses about the correlates, causes, and consequences of childhood
      sexual questioning. Participants were 182 children in the 4th through 8th grades.
      Compared with children more confident in their heterosexuality, sexual
      questioning children reported more impaired self-concepts, fewer same-sex-typed
      attributes (but not more cross-sex-typed attributes), a greater sense of feeling
      different from same-sex others, and lesser satisfaction with their gender
      assignment. Short-term longitudinal analyses indicated that sexual questioning is
      more likely a determinant than a consequence of these correlated variables.
      However, influences of sexual questioning on these outcomes were small.

PMID- 14700462
TI  - Predicting stability and change in toddler behavior problems: contributions of
      maternal behavior and child gender.
AB  - This study examined the stability and continuity of early-identified behavior
      problems and the factors associated with this stability. Children and their
      mothers (N=125) were seen when the children were 2 and 4 years of age. Maternal
      reports of child externalizing behavior and laboratory observations of child
      noncompliance were stable from age 2 to age 4. Early externalizing behaviors
      decreased over time; however, child noncompliance in the laboratory did not.
      Although few associations were found between maternal positive behavior and child
      behavior problems, maternal controlling behavior was related to increases in
      child behavior problems, particularly at high levels of both prior noncompliance
      and prior maternal control. Child noncompliance was predictive of increases in
      maternal controlling behavior over time.

PMID- 14700464
TI  - Object retrieval in the 1st year of life: learning effects of task exposure and
      box transparency.
AB  - Before 12 months of age, infants have difficulties coordinating and sequencing
      their movements to retrieve an object concealed in a box. This study examined (a)
      whether young infants can discover effective retrieval solutions and consolidate
      movement coordination earlier if exposed regularly to such a task and (b) whether
      different environments, indexed by box transparency, would impact the rate of
      learning and time of discovery of these solutions. Infants (N=12) were presented
      with an object retrieval task every week from 6 1/2 months of age until they were
      able to retrieve the toy from the box using coordinated two-handed patterns for 3
      weeks. To reach that criterion, infants tested with an opaque box took 2 1/2
      months and infants tested with a semitransparent box took 1 1/2 months. Both
      groups outperformed age-matched controls who received a one-time exposure to the
      task. Repeated exposure to the task and vision of the toy significantly enhanced
      this process of solution discovery.

PMID- 14700465
TI  - The relation of children's everyday nonsocial peer play behavior to their
      emotionality, regulation, and social functioning.
AB  - The relations of children's nonsocial behavior to their emotionality, regulation,
      and social functioning were examined in a short-term longitudinal study. Parents
      (primarily mothers) and teachers rated children's effortful regulation,
      emotionality, asocial behaviors, problem behaviors, and social acceptance, and
      children's nonsocial play behaviors were observed for two semesters. Peers also
      rated likability. Children's observed reticent activities were related to adults'
      ratings of high regulation, low externalizing problems, and high asocial
      behavior, as well as to low anger and low positive emotion. On the other hand,
      solitary play was associated with low positive emotion and low regulation over
      time and with high asocial behavior and high peer exclusion. Peer rejection
      mediated the relation of internalizing emotions (anxiety, low positive emotion)
      and regulation to solitary play later in the school year, and asocial play
      mediated the relation of internalizing emotions to both solitary and reticent
      play behavior.

PMID- 14700466
TI  - Are there biological programming effects for psychological development? Findings
      from a study of Romanian adoptees.
AB  - Associations between experiences and outcomes could be due to (a) continuation of
      adversity or (b) organismic changes, including experience-expectant and
      experience-adaptive developmental programming. The adoption into British families
      of children who had been reared in profoundly depriving institutions in Romania
      presented an opportunity to test mechanisms. Romanian children reared from
      infancy in very depriving institutions for periods up to 42 months were compared
      with 52 nondeprived UK-born children placed into adoptive families before the age
      of 6 months. The results at 6 years of age showed substantial normal cognitive
      and social functioning after the provision of family rearing but also major
      persistent deficits in a substantial minority. The pattern of findings suggests
      some form of early biological programming or neural damage stemming from
      institutional deprivation, but the heterogeneity in outcome indicates that the
      effects are not deterministic.

PMID- 14700468
TI  - Growth goals, maturity, and well-being.
AB  - In 2 studies (125 college students and 51 adults), 2 forms of growth goals
      (exploratory and intrinsic) were compared with 2 forms of personality development
      (social-cognitive maturity and social-emotional well-being). Participants whose
      narratives of major life goals emphasized conceptual exploration were especially
      likely to have high levels of maturity (measured as ego development; J.
      Loevinger, 1976), whereas those whose goals emphasized intrinsic interests (K. M.
      Sheldon & T. Kasser, 1995) were especially likely to have high levels of well
      being. Participants who had coherent hierarchies of growth goals on the levels of
      major life goals and everyday goals were especially likely to have high levels of
      personality development. Finally, growth goals accounted for some relationships
      between age and personality development. Growth goals are discussed in terms of
      intentional self-development and specific developmental paths.

PMID- 14700467
TI  - Mothers' behavior modifications during pretense and their possible signal value
      for toddlers.
AB  - An important issue for understanding early cognition is why very young children's
      real-world representations do not get confused by pretense events. One possible
      source of information for children is the pretender's behaviors. Pretender
      behaviors may vary systematically across real and pretend scenarios, perhaps
      signaling to toddlers to interpret certain events as not real. Pretender
      behaviors were examined in 2 experiments in which mothers were asked both to
      pretend to have a snack and really to have a snack with their 18-month-olds.
      Episodes were analyzed for condition differences in verbal and nonverbal
      behaviors, including smiling, looking, laughter, and functional movements.
      Reliable differences were found across conditions for several variables. In a 3rd
      experiment, children's apparent understanding of pretense in relation to their
      mothers' behaviors was examined, and significant associations were found with
      some of the mothers' behavioral changes but not others. This work provides a
      first inroad into the issue of how children learn to interpret pretense acts as
      pretense.

PMID- 14700469
TI  - Steady state analysis of metabolic pathways using Petri nets.
AB  - Computer assisted analysis and simulation of biochemical pathways can improve the
      understanding of the structure and the dynamics of cell processes considerably.
      The construction and quantitative analysis of kinetic models is often impeded by
      the lack of reliable data. However, as the topological structure of biochemical
      systems can be regarded to remain constant in time, a qualitative analysis of a
      pathway model was shown to be quite promising as it can render a lot of useful
      knowledge, e. g., about its structural invariants. The topic of this paper are
      pathways whose substances have reached a dynamic concentration equilibrium
      (steady state). It is argued that appreciated tools from biochemistry and also
      low-level Petri nets can yield only part of the desired results, whereas
      executable high-level net models lead to a number of valuable additional insights
      by combining symbolic analysis and simulation.

PMID- 14700470
TI  - The knowledge and expectations of parents about the role of antibiotic treatment
      in upper respiratory tract infection--a survey among parents attending the
      primary physician with their sick child.
AB  - BACKGROUND: Upper respiratory tract infections (URTI) are common. The etiologic
      factor is usually viral, but many physicians prescribe antibiotics. We aimed to
      evaluate parents' expectations of and knowledge about the role of antibiotics in
      childhood URTI. METHODS: The study was conducted in thirteen primary care
      pediatric clinics. Parents of children aged 3 months to 6 years who attended with
      URTI symptoms were included when it was the first attendance in the current
      illness. Questionnaire about the current illness, reasons for attending and
      expectations from the visit, knowledge about URTI was filled before the visit.
      RESULTS: In 122 visits the average age was 2.8 +/- 1.9 years. The main reasons
      for the visit were to avoid complications (81%) and to be examined (78%).
      Expected treatment was: cough suppressants (64%), anti-congestants (57%),
      paracetamol (56%), natural remedies (53%) and antibiotics (25%). In 28% the child
      had received antibiotics in past URTI. Only 37% thought that antibiotics would
      not help in URTI and 27% knew that URTI is a self-limited disease. 61% knew that
      URTI is a viral disease. Younger parental age and higher education were
      associated with lower expectations to receive antibiotics (p = 0.01, p < 0.005
      respectively). While previous antibiotic treatment (p < 0.001), past perceived
      complications (p = 0.05) and the thought that antibiotics help in URTI (p <
      0.001) were associated with a greater expectation for antibiotics. CONCLUSIONS: A
      quarter of the parents attending the physician with URTI are expecting to get
      antibiotics. Predictors were lower education, older parental age, receiving
      antibiotics in the past and the belief that antibiotics help in URTI.

PMID- 14700473
TI  - Phase II and phase III trials: docetaxel/irinotecan versus docetaxel/cisplatin in
      advanced non-small-cell lung cancer (WJTOG 9803).

PMID- 14700472
TI  - 25th European Society for Medical Oncology Congress. Hamburg, Germany. October 13
      17, 2000.

PMID- 14700474
TI  - Irinotecan/cisplatin versus vindesine/cisplatin versus irinotecan alone in
      advanced non-small-cell lung cancer.

PMID- 14700475
TI  - Effectiveness of radiation therapy on non-small-cell lung cancer.
AB  - Radiotherapy is an effective locoregional cancer treatment aimed at achieving
      tumor control. For almost a century, radiation has been used as a curative and/or
      palliative form of treatment alone or in combination with other treatment
      modalities for non-small-cell lung cancer. Trials are ongoing to investigate the
      value of altered fractionation radiation therapy alone or in combination with
      novel chemotherapy agents such as taxanes and gemcitabine, while monitoring for
      related toxicities. Attempts at minimizing the amount of normal tissue irradiated
      with three-dimensional treatment planning and/or protecting normal tissues with a
      radioprotector may allow for therapeutic escalation of radiation dose with
      further success at treating our nation's number one cause of cancer-related
      mortality.

PMID- 14700478
TI  - Radiosurgery and radiotherapy for non-small-cell lung cancer metastatic to brain.
AB  - Non-small-cell lung cancer metastatic to brain represents a common problem in
      oncology. Treatment modalities include stereotactic radiosurgery (SRS), whole
      brain radiotherapy (WBRT), surgical resection, supportive care, or a combination
      of these options. This review outlines therapeutic strategies for treatment with
      particular attention to the use of SRS. Radiosurgical technique, radiobiology,
      dose prescription, patient selection, and results of therapy are discussed. The
      term SRS describes a radiation procedure that utilizes a three-dimensional
      stereotactic localization system to precisely treat small intracranial targets
      with a single, large, highly focal radiation dose. Stereotactic radiosurgery is
      appealing for several reasons; it is minimally invasive, easily tolerated, and
      highly effective, and patients return to normal baseline function within 24
      hours. Stereotactic radiosurgery provides much higher control rates of treated
      lesions than does WBRT. Randomized trials are underway to ascertain the optimal
      role and timing of SRS in relation to WBRT in order to maximize control,
      survival, quality of life, and neuropsychological outcome.

PMID- 14700479
TI  - Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive
      small-cell lung cancer.
AB  - The purpose of this study was to examine the safety and efficacy of
      carboplatin/etoposide/paclitaxel in patients with untreated stage IV non-small
      cell lung cancer (NSCLC) and extensive small-cell lung cancer (SCLC). Carboplatin
      was administered intravenously (i.v.) at an area under the curve (AUC) of 6 with
      etoposide at either 80 or 100 mg/m2 i.v. days 1-3 and paclitaxel at 175 or 200
      mg/m2 i.v. over 3 hours along with 5 g/kg of granulocyte colony-stimulating
      factor subcutaneously on days 4-18, repeated every 3 weeks for 6 courses. Thirty
      one patients (five NSCLC and 26 SCLC) entered into this phase I study. The median
      age was 63 (range, 42 to 74 years), with 24 males and seven females. The
      recommended dose level for phase II testing was carboplatin AUC = 6, etoposide 80
      mg/m2 days 1-3, and paclitaxel 175 mg/m2 over 3 hours. With seven patients at
      this level, 14% had grade 4 neutropenia, 14% had grade 4 thrombocytopenia, none
      had grade 2/3 neurotoxicity, and no toxic deaths occurred. One of five (20%)
      patients with NSCLC responded, and 19 of 22 (86%) evaluable SCLC patients
      experienced a response to therapy. SCLC patients had a median survival of 10
      months. The combination of carboplatin/etoposide/paclitaxel has significant
      activity with acceptable toxicity in patients with extensive SCLC.

PMID- 14700480
TI  - Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as
      maintenance therapy for patients treated with chemotherapy for advanced non-small
      cell lung cancer.
AB  - This study was designed as a multicenter, randomized, double-blind, placebo
      controlled trial. Patients were randomized by center to placebo (16 patients,
      31%), oral bexarotene 300 mg/m2/day (21 patients, 40%), or oral bexarotene 600
      mg/m2/day (15 patients, 29%) following demonstration of stable or responsive
      disease after first-line chemotherapy. The study was prematurely terminated
      because of slow accrual after 54 patients enrolled. Median time to progression
      (TTP) from the beginning of study drug treatment was 56 days for placebo, 82 days
      for moderate-dose bexarotene (300 mg/m2/day), and 128 days for high-dose
      bexarotene (600 mg/m2/day) (P = 0.56, log-rank test). For prior chemotherapy
      responders only, median TTP from the beginning of study drug treatment was 56
      days for placebo, 146 days for moderate-dose bexarotene, and 177 days for high
      dose bexarotene. Of note, there were more chemotherapy responders randomized to
      the placebo group (63%) than the bexarotene treatment arms (48% and 47%), further
      supporting a bexarotene-related improvement in TTP. Bexarotene-related toxicity
      was manageable and consisted primarily of elevated serum triglycerides and
      asthenia, skin toxicity (dryness, peeling, flaking), thyroid dysfunction, and
      headache. Because this study was closed prematurely, it does not have the
      statistical power to detect differences among the treatment groups. This study
      shows that patients can tolerate bexarotene at initial doses up to 600 mg/m2/day
      after platinum-based chemotherapy and that bexarotene may have the potential to
      delay disease progression in patients with advanced non-small-cell lung cancer
      with previously stable or responsive disease following platinum-based
      chemotherapy.

PMID- 14700481
TI  - Effect of HER2/neu expression on survival in non-small-cell lung cancer.
AB  - Major prognostic factors for early-stage non-small-cell lung cancer (NSCLC) are
      tumor size and nodal status. It has been suggested that HER2/neu overexpression
      may be related to poor prognosis in NSCLC. We evaluated the significance of
      HER2/neu overexpression on survival in patients with NSCLC. Data were collected
      on 239 patients treated surgically for stage I/II NSCLC between 1987 and 1996.
      None of the patients received adjuvant chemotherapy or radiation. Formalin-fixed,
      paraffin-embedded tumor tissue samples were stained with p185/HER2 receptor
      antibody. Results were reported as positive (2+, 3+) or negative (0, 1+) (Group
      A). A separate analysis considered only 3+ as positive (Group B). HER2/neu
      overexpression was seen in 18% in Group A (43 of 239) and 6% in Group B (15 of
      239). HER2/neu overexpression was highest in bronchoalveolar cell carcinoma and
      adenocarcinoma. More stage I tumors were positive than stage II in both groups,
      but this was significant only in Group A (21% vs. 7%, P = 0.02). No difference
      was seen with age, gender, or grade for either group. In Group A, the relapse
      rate was 55% for HER2/neu-overexpressing tumors and 31% for HER2/neu-negative
      tumors (P = 0.003). Median time to relapse in patients with HER2/neu-positive
      tumors was 2.9 years; it was not reached in patients with HER2/neu-negative
      tumors. Median survival of patients with HER2/neu-positive tumors was 3.6 years
      compared to 5 years in patients with HER2/neu-negative tumors (P = 0.66). In
      Group B, the relapse rate was 60% for HER2/neu-overexpressing tumors and 33% for
      negative tumors (P = 0.036). Median time to relapse was 3.4 years in HER2/neu
      positive and had not been reached in negative tumors. There was no difference in
      5-year survival rates for both groups (47% for HER2/neu positive and 50% for
      negative, P = 0.66).

PMID- 14700482
TI  - Potential clinical application of antioncogene ribozymes for human lung cancer.
AB  - Non-small-cell lung cancer frequently contains oncogenetic defects (mutations in
      ras, retinoblastoma, and p53 genes) that contribute to disease pathophysiology.
      Recent studies and clinical trials have focused on gene therapy approaches that
      either replace the function of defective tumor-suppressor genes such as p53 or
      inactivate mutant oncogenes such as ras. Ribozymes are RNA molecules with highly
      specific intrinsic enzymatic activity against target RNA sequences, which can
      discriminate mutant sequences that differ by a single base from their wild-type
      counterparts. Following binding to the RNA substrate by base-pair
      complementation, the ribozyme cleaves the target RNA irreversibly, then releases
      itself for new rounds of subsequent cleavage, resulting in significantly improved
      target:effector stoichiometry as compared with antisense oligonucleotides of the
      same specificity. Transcript-specific ribozymes have been used extensively for
      experimental oncogene inactivation. Ribozymes are effective for targeting mutant
      ras, p53, or the multidrug-resistant gene product for lung cancer cells in vitro.
      However, their in vivo effect is not well defined against this malignancy. We
      recently characterized the antitumor properties of an anti-K-ras ribozyme
      specific for the K-ras codon 12 mutation (GGT-->GTT). When delivered as a
      transgene by an adenoviral vector (ADV), the K-ras ribozyme (KRbz) suppressed
      growth of lung tumor xenografts expressing the relevant mutation, whereas the
      corresponding antisense sequence lacking catalytic activity did not. Multiple
      intratumoral (3-5) injections of KRbz-ADV were effective in producing complete
      tumor regressions of preexisting tumor xenografts. Clinical trials are under
      consideration to examine the applicability of this anti-K-ras ribozyme for
      treatment of non-small-cell lung cancers expressing the relevant mutation.

PMID- 14700483
TI  - The role of positron emission tomography in evaluating mediastinal lymph node
      metastases in non-small-cell lung cancer.
AB  - Positron emission tomography (PET) is a modality that differentiates malignant
      from benign processes based upon metabolism rather than anatomy. A number of
      studies have confirmed improved accuracy of PET over computed tomography (CT),
      but until a few recent studies, most had failed to include satisfactory
      histologic confirmation. The objective of this study was to compare PET and CT to
      histologic staging of the mediastinum in patients with non-small-cell lung cancer
      (NSCLC). Histologic examination of mediastinal lymph nodes (MLNs) was performed
      on 40 patients with NSCLC at mediastinoscopy and/or at surgical resection. PET
      scans were interpreted by one of two nuclear medicine physicians, blinded to
      histology, using CT scans for anatomic localization. CT scans were independently
      evaluated for mediastinal lymphadenopathy. The overall accuracy, sensitivity, and
      specificity of PET were 78% (31 of 40), 67% (four of six), and 79% (27 of 34),
      respectively. The overall accuracy, sensitivity, and specificity of CT were 68%
      (27 of 40), 50% (three of six), and 71% (24 of 34), respectively. PET was
      superior to CT at correctly identifying mediastinal nodal metastases; however,
      both modalities were inferior to the gold standard of surgical staging. PET is
      more accurate than CT in staging the mediastinum of patients with NSCLC. PET
      failed to identify lymph node metastasis in 33% of patients with histologically
      proven MLN involvement, and false positives were present in 15%. At present,
      mediastinoscopy should remain the standard of care for preoperative mediastinal
      staging for NSCLC.

PMID- 14700484
TI  - Medical research in Pakistan.

PMID- 14700485
TI  - Itraconazole pulse therapy in the treatment of disto-lateral subungual
      onychomycosis.
AB  - OBJECTIVE: To assess the efficacy of itraconazole pulse therapy in disto-lateral
      subungual onychomycosis. DESIGN: Quasi interventional study. PLACE AND DURATION
      OF STUDY: The study was conducted at the Department of Dermatology, KEMC/Mayo
      Hospital, Lahore, during the period from 1996-1998. SUBJECTS AND METHODS: Sixty
      seven patients, ages ranging from 19 to 55 years, with disto-lateral subungual
      onychomycosis were enrolled in the study period. Therapy was started with short
      pulse doses of itraconazole 200 mg twice daily for one week followed by a
      medicine-free interval of three weeks. Pulses were administered for two
      consecutive months in fingernail and three months for toenail onychomycosis.
      Patients were followed up to six months for fingernail onychomycosis and nine
      months for toenail onychomycosis. RESULTS: Out of 67 cases, there were 62
      evaluable patients. Trichophyton rubrum was the most common pathogen, isolated in
      42 (67.8%) followed by Candida in 11 (17.8%), T. violaceum in 5 (8%), T.
      interdigitale in 3 (4.8%) and Epidermophyton floccosum in one (1.6%). Fingernails
      were affected in 46 cases whereas 16 had toenail infection. Clinical cure in
      finger and toenail onychomycosis was seen in 41 (89%) and 13 (81.2%) patients,
      respectively while mycological cure in 43 (93.5%) and 14 (87.5%) patients,
      respectively with itraconazole pulse therapy. CONCLUSION: Itraconazole was found
      to be effective, well-tolerated and safe therapy for disto-lateral subungual
      onychomycosis.

PMID- 14700486
TI  - Knowledge and attitude of older women towards menopause.
AB  - OBJECTIVE: To determine the knowledge and attitude towards menopause among
      postmenopausal women seeking gynecological treatment. DESIGN: A descriptive cross
      sectional survey based on sample of convenience. PLACE AND DURATION OF STUDY: The
      study was conducted at the Gynecology outpatient department of MCH Center, PIMS,
      Islamabad from 1st June to 31st September, 2002. SUBJECTS AND METHODS: Seventy
      postmenopausal women over 45 years of age were interviewed. RESULTS: The mean age
      of respondents was 54.4 years. Fifty-two (74.3%) women knew about menopause, 39
      (55.7%) were aware of symptomatology while only 7 (10%) knew sequelae of
      menopause. Fifty-three (75.7%) women were satisfied with cessation of
      menstruation and only 17 (24.3%) desired to continue menstruation. Twenty-four
      (34.3%) respondents were unhappy with their menopausal status. Thirty-two (45.7%)
      women were content with their present sexual relations, 18 (25.7%) were
      dissatisfied and 20 (28.6%) had no sexual activity. Fifty-two (74.3%) women felt
      a need for health education on menopause in educational institutions. Thirty
      three (47.1%) considered treatment of menopause necessary. Four (5.7%) were aware
      of any treatment of menopause and 55 (78.6%) desired to learn more about
      menopause. CONCLUSION: Women have different views about menopause, few see it as
      a medical condition requiring treatment, whereas a majority consider it a natural
      transition. There was dearth of knowledge regarding significance of menopause.

PMID- 14700487
TI  - Fine needle aspiration biopsy of soft tissue tumours.
AB  - OBJECTIVE: To determine the usefulness, limitations and diagnostic accuracy of
      fine needle aspiration biopsy (FNAB) in soft tissue tumours. DESIGN: Cross
      sectional analytical (comparative) study. PLACE AND DURATION OF STUDY: Department
      of Histopathology, Armed Forces Institute of Pathology, Rawalpindi. MATERIALS AND
      METHODS: A total of 78 soft tissue tumours were subjected to FNAB from May 2000
      to April 2002. Adequate aspirate was obtained in 69 patients. The smears were
      stained with Haematoxylin and Eosin (HE) and May-Grunwald-Giemsa (MGG) stains.
      FNAB smears were put into three categories i.e. benign, borderline or malignant.
      A definite diagnosis was also given where possible. Tissue biopsies were received
      in 38 of these patients. Routine HE staining was done in each case along with
      special stains and immunohistochemistry where required. RESULTS: Out of 69
      tumours, 30 were categorised as benign, 9 as intermediate and 30 as malignant.
      Lipomas were the most common benign tumour while small round blue cell tumours
      constituting 7 cases (23%) were the commonest malignancy. FNAB-histological
      correlation showed all tumours reported as benign on FNAB to be confirmed as
      such. There was only one false positive diagnosis on FNAB. All cases placed in
      intermediate category were found to be malignant on histopathology. Considering
      intermediate cases alternatively as benign and malignant revealed sensitivity of
      80.6% and 100%, specificity of 85.7% and 85.7% and accuracy of 81.6% and 97.4%
      respectively. CONCLUSION: Majority of soft tissue tumours can be categorized on
      FNAB with high degree of accuracy. The tumours placed in intermediate category
      should be subjected to biopsy or excision as it is more likely that they turn out
      to be malignant.

PMID- 14700488
TI  - Neonatal sepsis in hospital-born babies: bacterial isolates and antibiotic
      susceptibility patterns.
AB  - OBJECTIVE: To determine the frequency of bacterial isolates from neonatal blood
      cultures and their susceptibility patterns in hospital-born babies having sepsis.
      DESIGN: An observational study. PLACE AND DURATION OF STUDY: Obstetrics Unit and
      Special Care Baby Unit of Khyber Teaching Hospital, Peshawar from 1st January to
      31st December 2001. SUBJECTS AND METHODS: This study was carried out on the
      neonates born and admitted in hospital with positive blood culture reports. Early
      onset neonatal sepsis (EONNS) and late onset neonatal sepsis (LONNS) were defined
      as illness appearing from birth to seven days and from eight to twenty-eight days
      postnatal age respectively. The blood culture reports were analyzed by SPSS
      package and cross tabulation was done. RESULTS: One hundred and twelve hospital
      born babies presented with sepsis. Sixty-seven neonates had positive cultures.
      Escherichia coli (E. coli) was the commonest organism causing EONNS (35; 77.1%)
      followed by Pseudomonas (4; 8.9%), Klebsiella (4; 8.9%) and Staphylococcus aureus
      (2; 4.4%) respectively. In the LONNS E. coli (19; 77.3%) was the commonest
      followed by Staphylococcus and Pseudomonas (2; 9% each) and Klebsiella (1; 4.5%).
      The gram-negative organisms showed high degree of resistance to commonly used
      antibiotics, ampicillin (79.3%), amoxicillin (74.6%) and ceftazidime (71.6%),
      cefotaxime (55.2%) and comparatively low resistance to gentamicin (43.2%),
      tobramycin (34.3%), imipinem (23.6%), amikacin (22.3%), ofloxacin and
      ciprofloxacin (11.9%) respectively. Staphylococcus aureus showed almost the same
      resistance to ampicillin, 75%, and comparatively low resistance to the rest of
      the antibiotics as compared to the gram-negative organisms. CONCLUSION: Neonatal
      sepsis is mainly caused by gram-negative organisms, which are developing
      resistance to commonly used antibiotics.

PMID- 14700489
TI  - High dose rate intraluminal brachytherapy in combination with external beam
      radiotherapy for palliative treatment of cancer rectum.
AB  - OBJECTIVE: To evaluate the feasibility, efficacy and toxicity of High Dose Rate
      Intraluminal Brachytherapy (HDRILB) in combination with External Beam
      Radiotherapy (EBR) used in the palliative treatment of selected patients of
      adenocarcinoma rectum. DESIGN: A prospective pilot study. PLACE AND DURATION OF
      STUDY: The study was conducted at the Institute of Radiotherapy and Nuclear
      Medicine (IRNUM), Peshawar. The study started in April 1996 and the patients
      accrual was completed in June 1997. PATIENTS AND METHODS: The patients with
      adenocarcinoma rectum, who refused surgery, had contraindications for surgery or
      had advanced and/or metastatic disease were treated with HDRILB in combination
      with external beam radiotherapy (EBR). The apparatus used for HDRILB was Ralstron
      20B remote afterloading unit with 60Co stepping source. Indigenously designed
      rectal applicators were used. The EBR was delivered through Pheonix 60Co
      teletherapy machine (Theratron AECL). The data for symptom burden and symptomatic
      relief was analyzed by applying Likert's method of summated scales. RESULTS: Data
      was analyzed after one week and at the end of the treatment. After one week of
      treatment, the relief in pain and bleeding per rectum (P/R) was 97%. Excellent
      palliation was achieved at the end of the treatment when perineal pain and
      bleeding P/R were relieved in 100%, discharge P/R in 87% and tenesmus in 93% of
      the cases. CONCLUSION: The use of HDRILB in combination with EBR can provide
      quick relief of symptoms in selected patients of adenocarcinoma rectum. This
      combination has an excellent palliative value because of its effectiveness,
      acceptable toxicity and overall short treatment duration.

PMID- 14700491
TI  - Retained sponge after abdominal surgery.
AB  - OBJECTIVE: To study the cause and clinical presentation along with clinical
      course (cooperative and postoperative) of retained abdominal sponge. DESIGN:
      Observational case series. PLACE AND DURATION OF STUDY: Surgical Department,
      Bahawal Victoria Hospital, Bahawalpur, from April 1, 2000 to August 31, 2002.
      MATERIALS AND METHODS: The study included 12 patients. All the patients, who
      presented to surgical department during the stated period with retained abdominal
      sponge postoperatively, were included in the study. Retained abdominal foreign
      bodies, other than the surgical sponge, were excluded. RESULTS: A total of 12
      patients presented with retained abdominal sponge. Out of these, 33.33% were
      males and 66.66% females. Modes of presentation were intestinal obstruction,
      58.33%, discharging sinus, 41.67%, intraabdominal abscess, 16.67%, peritonitis,
      16.67% and mass abdomen, 8.33%. One death followed despite provision of due care.
      CONCLUSION: Retained surgical sponge is a potentially lethal condition and all
      preventive measures should be taken to avoid this condition.

PMID- 14700490
TI  - Is mechanical bowel preparation really necessary in colorectal surgery?
AB  - OBJECTIVE: To determine the outcome of colorectal surgery without mechanical
      bowel preparation. DESIGN: A descriptive, analytical and observational study.
      PLACE AND DURATION OF STUDY: Combined Military Hospital, Kharian and Pano Aqil,
      from September 1998 to April 2003. SUBJECTS AND METHODS: Forty-seven patients
      underwent debridement/resection and repair/primary anastomosis of colon and upper
      rectum without bowel preparation. Of these, 16 patients were operated in
      emergency. The anastomosis was carried out with polyglactin (vicryl) interrupted,
      full thickness single layer and no patient had defunctioning colostomy. Third
      generation cephalosporin, cefotaxime or ceftazidime and metronidazole were given
      perioperatively, repeated during surgery if lasted for more than 2 hours and
      continued for 3-5 days postoperatively. RESULTS: Anastomoses were ileocolic in
      29.7%, colicocolic in 61.7% and colorectal in 14.8% cases. Anastomotic failure
      was seen in 4.2% and wound infection in 8.5% cases. There was one mortality
      (2.1%) due to unrelated cause. CONCLUSION: Mechanical bowel preparation is not
      necessary for safe colorectal surgery.

PMID- 14700492
TI  - Frequency, presentation and postintervention prognosis of chondroblastoma.
AB  - OBJECTIVE: To evaluate the frequency of clinico-radiological presentation and the
      prognosis after treatment of chondroblastoma. DESIGN: A descriptive,
      observational study. PLACE AND DURATION OF STUDY: The study was carried out at
      the Department of Orthopaedic Surgery, JPMC, Karachi over the period of 16 years,
      January 1986 to June 2002. METHODOLOGY: Patients in teenage, presenting with
      signs and symptoms of a primary bone tumours, were included by retrospectively
      reviewing the tumour registry record. Detailed scrutiny of clinical record was
      carried out to analyze the clinico-radiological presentation and posttreatment
      prognosis criteria of healing was symptom-free centripetal and homogeneous
      ossification. RESULTS: Seven (1.24%) out of 563 primary bone tumour cases were
      chondroblastoma. The clinico-radiological presentation in the 2 out of 7 (28.57%)
      cases was classical, 2 simulated osteomyelitis and other 3 as chondromyxoid
      fibroma, aneurysmal bone cyst and giant cell tumour. Lesions were treated with
      curettage and bone grafting. One patient (14.28%) developed recurrence within 2
      years after curettage and healed after re-curettage and bone grafting. Five out
      of 7 (71.42%) tumours showed good response and 2 out of 7 (28.57%) showed
      satisfactory response. CONCLUSION: Chondroblastoma is very rare benign primary
      bone tumour with high local recurrence rate. The lesions confined to epiphysis of
      weight-bearing bone present early with symptoms of mild arthritis. Lesions in non
      weight-bearing bones often present late and simulates epiphysio-metaphyseal
      tumours. Lesions heals with centripetal healing and need more than 2 years follow
      up to achieve recurrence-free healing.

PMID- 14700493
TI  - Treatment of necrotizing fasciitis with quinolones.
AB  - OBJECTIVE: To evaluate the effect of high dose quinolones therapy in patients
      with necrotizing fasciitis. DESIGN: Descriptive analytical study. PLACE AND
      DURATION OF STUDY: The department of Plastic and reconstructive surgery,
      Hayatabad Medical Complex, Peshawar, from January 2001 to March 2002. SUBJECTS
      AND METHODS: Twenty consecutive patients, diagnosed with necrotizing fasciitis,
      were treated with intravenous quinolones (400 mg 8 hourly). The response was
      evaluated in terms of subsidence of fever and C-reactive proteins levels.
      RESULTS: Majority of the patients was male (60%). Lower limb involvement was most
      commonly involved (70%). The most common initiating cause was injection abscess
      (45%). Majority of the cultures showed polymicrobial infection (90%). The most
      common isolate was Streptococcus pyogenes (65%). Majority of the patients showed
      excellent response with intravenous quinolones (Ciprofloxacin) in high doses in
      24-48 hours. Only two patients (10%) failed to respond to therapy due to severe
      infection and delay in seeking treatment. CONCLUSION: Intravenous quinolones
      (Ciprofloxacin) in high doses are effective in controlling necrotizing soft
      tissue infections.

PMID- 14700494
TI  - Cutis marmorata telangiectatica congenita.
AB  - A case of cutis marmorata telangiectatica congenita (CMTC) is reported. A young
      girl had an unusual presentation with sclerosis in the skin lesions, senile
      features, hypoplasia of the mandible, transverse nail dystrophy, and transverse
      toe defects resembling Adams-Oliver syndrome. These associated abnormalities are
      very rare and some have not been documented before with CMTC. The possible
      relationship of CMTC with Adams-Oliver syndrome is also discussed.

PMID- 14700495
TI  - Situs ambiguous.
AB  - The case of a female child is described who presented with recurrent respiratory
      infections and "recurrent right subphrenic abscess." Detailed radiological work
      up identified situs ambiguous abdominis with bronchiectasis, duodenal
      malrotation, umbilical hernia and spina bifida.

PMID- 14700496
TI  - Angiodysplasia of upper gastrointestinal tract with coagulopathy.
AB  - A combination of duodenal telangiectasia with factor X deficiency presenting as
      recurrent malaena is rarely reported. Pylorus preserving pancreaticoduodenectomy
      done under cover of prothrombin complex resulted in complete recovery.
      Histopathology was consistent with angiomatosis. It is suggested that in managing
      a case of upper gastrointestinal bleeding, besides establishing the source of
      bleeding, it is important to detect underlying coagulopathy.

PMID- 14700497
TI  - Intestinal obstruction due to mesenteric panniculitis.
AB  - This report describes a case of mesenteric panniculitis in a 40-year-old male who
      presented with features of intestinal obstruction. Computed tomography scan
      showed a mass in the mesentery of small bowel. Resection of mass with associated
      small bowel and anastomosis resulted in complete recovery of the patient.

PMID- 14700498
TI  - Brainstem encephalitis with Kikuchi-Fujimoto disease.
AB  - A case of young woman is described who developed clinical and MRI features of
      brainstem encephalitis in the setting of fever and cervical lymphadenopathy.
      Lymph node biopsy revealed histiocytic necrotizing lymphadenitis (Kikuchi
      Fujimoto disease), which may reflect host response to an unspecified immune
      insult.

PMID- 14700499
TI  - Ruptured cornual pregnancy.
AB  - A case of ruptured cornual pregnancy is presented here. The patient presented
      with history of 30 weeks gestational amenorrhoea and pain in the lower abdomen
      and epigastrium for the last seven days. Ultrasound revealed a 29 weeks abdominal
      pregnancy with blood in the pelvic cavity. On laparotomy, there was a ruptured
      right cornual pregnancy, treated cornual resection and uterine repair. An alive
      male baby of one kg weight was delivered from the resected cornua of the uterus.

PMID- 14700500
TI  - Atretic fronto-ethmoidal encephalocele.
AB  - This case report describes a 4 months old infant with a lump on forehead since
      birth. The lump turned out to be an atretic encephalocele. Herniation of brain
      matter through scalp suture lines during intrauterine life is a rare happening.
      Congenital and environmental factors have been implicated.

PMID- 14700501
TI  - Fungal infections in neutropenic cancer patients.
AB  - Invasive fungal infections are important causes of morbidity and mortality in
      cancer patients with prolonged neutropenia following chemotherapy. Recent trends
      indicate a change toward infections by Aspergillus species, non-albicans species
      of Candida, and previously uncommon fungal pathogens. These have decreased
      susceptibility to current antifungal agents. In the last decade there has been
      much effort to find solution for these changing trends. This article reviews
      current approaches to prevention and treatment of opportunistic fungal infections
      in postchemotherapy neutropenic patients and discusses future antifungal
      approaches and supportive methods.

PMID- 14700502
TI  - Communication skills of family physicians in a doctor-patient consultation.

PMID- 14700503
TI  - Increased risk of cervical canal infections with intracervical foley catheter.

PMID- 14700504
TI  - Plasma renin activity levels in hypertensive persons: their wide range and lack
      of suppression in diabetic and in most elderly patients.
AB  - BACKGROUND: The renin-angiotensin system (RAS) maintains hemodynamic integrity by
      modulating both volume and vasoconstriction through a cybernetic feedback control
      mechanism. In addition, angiotensin II, the active component of the RAS, can be
      vasculotoxic and, in hypertensive individuals, is associated with increased
      cardiovascular morbidity and mortality. The objective of this study was to
      determine the distribution and determinants of plasma renin activity (PRA) in a
      representative sample of hypertensive persons. METHODS: We systematically
      measured PRA in 4170 untreated participants in a systematic work site-based,
      hypertension treatment program. RESULTS: In this multiethnic employed population,
      patients were classified as follows: low renin, <0.65 ng/mL/h (30% of the
      sample); medium renin, 0.66 to 4.5 mg/mL/h (60%); or high renin, >4.5 ng/mL/h
      (10%). Low renin patients were more likely to be African American, female, and
      slightly older. However, the majority of women and African American individuals
      were not low renin. The 469 diabetic subjects distributed across renin
      categories, as did the group as a whole. CONCLUSIONS: This systematic study of
      PRA in a large community sample of hypertensive patients reveals a wide
      distribution of activity level, with identifiable differences according to
      ethnicity, age, and sex but not diabetic status. However, these demographic
      differences were more quantitative than qualitative and do not provide a useful
      basis for estimation of the activity of the RAS. Instead, in hypertensive
      subjects, direct measurement of PRA is necessary, both for prognosis and for
      guiding hypertensive therapy.

PMID- 14700505
TI  - Angiotensinogen gene polymorphisms: relationship to blood pressure response to
      antihypertensive treatment. Results from the Swedish Irbesartan Left Ventricular
      Hypertrophy Investigation vs Atenolol (SILVHIA) trial.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is important for the
      development of hypertension, and several antihypertensive drugs target this
      system. Our aim was to determine whether specific single nucleotide polymorphisms
      (SNPs) in RAAS genes were related to the blood pressure (BP) lowering effect of
      antihypertensive treatment. METHODS: Patients with mild to moderate primary
      hypertension and left ventricular hypertrophy were randomized in a double-blind
      fashion to treatment with either the angiotensin II type 1 receptor antagonist
      irbesartan (n = 48) or the beta(1)-adrenergic receptor blocker atenolol (n = 49)
      as monotherapy. A microarray-based minisequencing system was used to genotype 30
      SNPs in seven genes in the RAAS. These polymorphisms were related to the
      antihypertensive response after 12 weeks treatment. RESULTS: The BP reductions
      were similar in the atenolol and the irbesartan groups. Presence of the
      angiotensinogen (AGT) -6A allele or the AGT 235T allele were both associated with
      the most pronounced systolic BP response to atenolol treatment (P =.001 when -6
      AA+AG was compared with GG and P =.008 for presence of the 235T variant compared
      with 235 MM). CONCLUSIONS: We found that SNPs in the angiotensinogen gene were
      associated with the BP lowering response to atenolol. This study is limited by a
      relatively small sample size, and the results should therefore be viewed as
      preliminary. Despite this limitation, these results illustrate the potential of
      using SNP genotyping as a pharmacogenetic tool in antihypertensive treatment.

PMID- 14700506
TI  - Perindopril effects on ambulatory blood pressure: relation to sympathetic nervous
      activity in subjects with diabetic nephropathy.
AB  - BACKGROUND: Few studies have reported the effect of angiotensin-converting enzyme
      inhibitors on 24-h blood pressure (BP) and regulation of sympathetic nervous
      activity in hypertensive patients with diabetic nephropathy. Using ambulatory BP
      monitoring (ABPM) devices equipped with spectral analysis of heart rate
      variability, we assessed the effects of perindopril on 24-h BP and autonomic
      nervous activity in these patients. METHODS: Thirty-four hypertensive patients
      with non-insulin-dependent diabetic nephropathy underwent ABPM before and after
      treatment with perindopril (final dose: 4.9 +/- 1.8 mg/d). Simultaneously,
      spectral analysis was performed to calculate the high frequency components (HF)
      as a marker of parasympathetic nervous activity, and the low frequency components
      (LF)/HF ratios as an index of the sympathovagal balance. RESULTS: Perindopril
      significantly and equally decreased the waking and sleeping BP in the diabetic
      patients. During the sleeping period, the magnitude of change of mean BP induced
      by perindopril correlated inversely with the sleeping/waking ratio of mean BP
      before treatment. However, there was no correlation between these parameters
      during the waking period. Perindopril decreased both waking and sleeping LF/HF
      ratios, although no differences in HF components were observed between before and
      after treatment. CONCLUSIONS: In patients with diabetic nephropathy, perindopril
      decreased 24-h BP. Spectral analysis suggested that this finding was partially
      related to inhibited sympathetic nervous activity. During sleeping periods, the
      BP-lowering effect of perindopril was more pronounced in patients showing no
      nocturnal decrease in BP. Perindopril may be a potent antihypertensive agent to
      reduce increased nocturnal BP, a risk factor of target organ damage in these
      patients.

PMID- 14700507
TI  - Effect of sodium on blood pressure, cardiac hypertrophy, and angiotensin receptor
      expression in rats.
AB  - BACKGROUND: Sodium-induced hypertensive cardiac hypertrophy is related to
      pressure and volume overload. METHODS: Wistar rats were exposed to low and high
      sodium diet for 8 weeks. Angiotensin II receptor mRNA, abundance of p38 mitogen
      activated protein kinase (p38MAPK), vasoconstriction of aortic rings, and
      angiotensin II-induced calcium increase were investigated. RESULTS: Rats on high
      sodium diet showed significantly elevated blood pressure. Heart weight, AT1
      receptor mRNA in cardiac and aortic tissues, and abundance of p38MAPK were
      significantly increased in rats on high sodium diet. CONCLUSIONS: Increased AT1
      receptor expression and angiotensin II-induced calcium increase are compensatory
      effects in sodium-induced hypertension.

PMID- 14700508
TI  - Enhanced heme oxygenase-mediated coronary vasodilation in Dahl salt-sensitive
      hypertension.
AB  - BACKGROUND: Cardiovascular tissues express heme oxygenase (HO), which metabolizes
      heme to form carbon monoxide (CO). Carbon monoxide promotes relaxation of
      coronary vascular smooth muscle. Increased HO-1 expression provides
      cardioprotection during certain pathologic conditions. On a high salt (HS) diet
      Dahl salt-sensitive (DS) rats develop hypertension that is accompanied by left
      ventricular hypertrophy, whereas Dahl salt-resistant rats (DR) do not. This study
      tests the hypothesis that cardiac HO-1 expression is increased in DS rats with
      salt-induced hypertension and provides cardioprotection by promoting coronary
      vasodilation. METHODS: Male DS and DR rats were placed on a HS (8% NaCl) or low
      salt (LS, 0.3% NaCl) diet for 4 weeks. Cardiac HO isoform expression were
      determined by immunohistochemistry. Experiments used isolated paced Langendorff
      hearts perfused at a constant flow. Changes in coronary perfusion pressure and
      left ventricular contractility (dP/dt(max)) were measured in response to an
      inhibitor of HO, chromium mesoporphyrin (CrMP). RESULTS: With respect to the LS
      group, DS rats on HS diet showed elevated mean arterial pressure and increased
      heart weight. Coronary arterial HO-1 immunostaining was enhanced in HS rats, but
      HO-2 staining was similar in both groups. In isolated Langendorff-hearts the HO
      inhibitor CrMP increased coronary perfusion pressure and calculated coronary
      resistance, and decreased left ventricular contractility (dP/dt(max)) in both
      groups, but the response was exaggerated in HS rat hearts. In the DR strain, HS
      diet did not augment CrMP responses and had no effect on any of the parameters
      measured with respect to the LS diet. CONCLUSIONS: These findings suggest that
      coronary HO-1 expression is increased to promote enhanced coronary vasodilation
      in DS rats with salt-induced hypertension.

PMID- 14700509
TI  - The role of oxidative stress in salt-induced hypertension.
AB  - BACKGROUND: Impairment of endothelial function during hypertension is associated
      with increased production of superoxide radicals and reduced antioxidants. We
      investigated the involvement of oxidative stress in Dahl salt-sensitive (SS) and
      salt-resistant (SR) rats. METHODS: For a 2-week period, male rats were fed either
      high salt (HS; 8% sodium chloride) or low salt (LS; 0.3% sodium chloride) diets.
      Before and weekly on the diets, mean arterial pressure (MAP) and heart rate were
      measured by tail-cuff plethysmography. At the end of the experiment, plasma and
      tissue samples were collected for analysis of nitric oxide, prostacyclin,
      glutathione, and isoprostane. RESULTS: The MAP was increased in SS rats on HS
      diet, but not in those on a LS diet or in SR rats on either diet. Plasma levels
      of nitric oxide were reduced in SS rats on HS diet. Plasma prostacyclin levels in
      SS rats on either diet were lower than SR on LS diet. Increased dietary salt
      reduced plasma prostacyclin levels in SR, but not in SS rats. Plasma total 8
      isoprostane was elevated in both SS and SR rats on HS diet compared with either
      strain on LS diet. Plasma levels of total glutathione were reduced in SS compared
      with SR rats, regardless of the level of dietary salt intake. The whole blood
      ratio of reduced-to-oxidized glutathione (GSH/GSSG) as well as the kidney total
      glutathione were lower in SS rats on HS diet. Aortic superoxide production in
      both strains on HS diet was increased compared with the animals on LS diet.
      CONCLUSIONS: These data suggest that HS diet may indirectly induce endothelial
      dysfunction through intermediate mechanisms that are associated with oxidative
      stress.

PMID- 14700510
TI  - Effect of antihypertensive monotherapy and combination therapy on arterial
      distensibility and left ventricular mass.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and calcium channel
      blockers (CCBs) increase arterial compliance and decrease left ventricular mass
      in hypertensive patients. This study examined whether combined therapy has
      greater arterial and cardiac effects than doubled doses of the individual drugs.
      METHODS: This prospective, randomized, open-label study enrolled 106 patients
      aged >/=18 years with mild-to-moderate hypertension. Patients were randomized to
      5 mg of amlodipine or 20 mg of benazepril for 2 weeks; then, depending on
      randomization assignment, they were force-titrated to 10 mg of amlodipine or 40
      mg of benazepril monotherapy, or to combination amlodipine (5 mg) and benazepril
      (20 mg) treatment for 22 weeks. Arterial distensibility was assessed using the
      DynaPulse ambulatory system, and left ventricular mass was assessed by
      echocardiography. RESULTS: Combination therapy (0.71% +/- 0.51% mL/mm Hg)
      increased arterial distensibility more than amlodipine (0.28% +/- 0.69% mL/mm Hg;
      P =.008) or benazepril (0.39% +/- 0.62% mL/mm Hg; P =.03) monotherapies. Left
      ventricular mass decreased more with combination treatment (65 +/- 56 g) than
      with amlodipine (28 +/- 4 g; P <.02); the difference from benazepril (42 +/- 50
      g) was not significant. CONCLUSIONS: Combined ACE inhibitor and CCB treatment was
      more efficacious than high doses of the individual agents in increasing arterial
      compliance and reducing left ventricular mass. These findings indicate that
      appropriately selected combinations of antihypertensive drugs might have enhanced
      cardioprotective effects.

PMID- 14700511
TI  - Ethnic differences in left ventricular structure: relations to hemodynamics and
      diurnal blood pressure variation.
AB  - BACKGROUND: Previous studies have suggested that African Americans have a greater
      left ventricular relative wall thickness than whites with similar levels of blood
      pressure (BP), whereas other investigators have documented an attenuated
      nocturnal decline in BP and early remodeling of the resistance vessels in African
      Americans. METHODS: To further evaluate the contributions of diurnal BP variation
      and vascular remodeling to ethnic differences in left ventricular geometry, we
      measured ambulatory BP, systemic hemodynamics, minimum forearm vascular
      resistance, and left ventricular structure in a biracial sample of 171 men and
      women between the ages of 25 and 45 years. RESULTS: Despite similar resting BPs,
      African Americans had a greater indexed peripheral resistance, a greater minimal
      forearm vascular resistance, and a smaller nocturnal decline in BP than white
      subjects. African Americans also had a greater left ventricular relative wall
      thickness (0.41 +/- 0.07 v 0.38 +/- 0.08, P =.048) and a trend toward a greater
      indexed left ventricular mass (41.1 +/- 8.7 v 38.6 +/- 8.6 g/m(2.7), P =.087).
      Ethnic differences in relative wall thickness were no longer significant when
      adjusted for either indexed peripheral resistance (P =.173) or sleep systolic BP
      (P =.124). CONCLUSIONS: In our cohort of young men and women, African Americans
      had a greater left ventricular relative wall thickness than whites with similar
      levels of resting BP. This early concentric remodeling of the left ventricle in
      African Americans may be mediated, in part, by hemodynamic influences, including
      a greater peripheral vascular resistance and a smaller nocturnal decline in BP.

PMID- 14700512
TI  - Association between different measurements of obesity and the incidence of
      hypertension.
AB  - BACKGROUND: Obesity is a risk factor for the incidence of hypertension, but it is
      still unclear whether this risk can be better estimated by body mass index (BMI)
      or waist circumference (WC). METHODS: In the baseline evaluation of a population
      based cohort, 1089 adults answered a pretested questionnaire and had their
      baseline blood pressure (BP) and anthropometric measurements assessed according
      to standardized recommendations. Excluding the individuals with hypertension at
      baseline, and those deceased or lost during the follow-up, 592 individuals (80.5%
      of those eligible) were visited again. Obesity was defined as BMI >/=30 kg/m(2)
      for both genders, and WC >/=102 cm for men and WC >/=88 cm for women. Incident
      cases of hypertension were characterized by BP >/=140/90 mm Hg or use of BP
      medication in the follow-up visit. RESULTS: After a mean follow-up of 5.6 +/- 1.1
      years, 127 incident cases of hypertension were identified. The hazard ratios (Cox
      model), adjusted for age and baseline systolic BP (95% CI and P), for BMI higher
      than 30 kg/m(2) were 1.08 (0.52-2.24, P =.82) in men and 1.74 (0.93-3.26, P =.08)
      in women. The corresponding figures were 1.78 (0.76-4.09, P =.18) for men with WC
      >/=102, and 1.72 (1.09-2.73, P =.02) for women with WC >/=88 cm. CONCLUSIONS: We
      conclude that the risk for hypertension may be better identified by obesity
      defined by higher WC than higher BMI.

PMID- 14700513
TI  - Comparison of the Omron HEM-637 wrist monitor to the auscultation method with the
      wrist position sensor on or disabled.
AB  - BACKGROUND: To determine whether the Omron HEM637 wrist model with the wrist
      positioning sensor turned on (Son) is more accurate relative to upper arm
      auscultation by trained professionals than when the sensor was manually turned
      off (Soff). METHODS: Forty-four subjects, at least 30 years old, had repeated,
      sequential dual-observer upper arm auscultatory measurements (5 to 6 each) and
      oscillometric Omron HEM637 wrist measurements (4 each). Nineteen subjects were
      assigned to the wrist sensor On group and 25 were assigned to the wrist sensor
      Off group. A total of 425 auscultatory and 164 wrist measurements were analyzed.
      RESULTS: The Omron HEM-637 measured the blood pressure (BP) with equal accuracy
      to the observers using the auscultatory technique (difference -1.37 +/- 8.51/3.47
      +/- 8.07 mm Hg, P =.71/.14). The wrist sensor did improve the accuracy of the
      measurements compared to the subjects that had the sensor deactivated. The sensor
      On group (Son) measured the systolic BP (0.82 +/- 9.83 mm Hg) and diastolic BP (
      0.72 +/- 9.07 mm Hg) statistically the same as by auscultation (P =.86 for
      systolic BP and P =.83 for diastolic BP). The sensor Off (Soff) group measured
      the SBP (-3.03 +/- 7.12 mm Hg) and diastolic BP (-5.56 +/- 6.68 mm Hg)
      statistically different than auscultation (P =.46 for systolic BP and P =.02 for
      diastolic BP). The higher (negative) measurement for both the systolic BP and
      diastolic BP suggests that the average position of the wrist was 1.75 inches (4.4
      cm) below the heart level in this group with the sensor off. CONCLUSIONS: This
      study demonstrated that the Omron HEM-637 monitor with a wrist sensor more
      accurately measured BP compared to the same model with the sensor turned off.

PMID- 14700514
TI  - Increased calcium and decreased magnesium concentrations and an increased
      calcium/magnesium ratio in spontaneously hypertensive rats versus Wistar-Kyoto
      rats: relation to arteriosclerosis.
AB  - Alterations in the metabolism of calcium and magnesium have been implicated in
      the pathogenesis of primary hypertension. Calcium influx across the external
      cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role
      in the control of cellular excitation contraction and impulse propagation.
      Intracellular calcium and magnesium concentrations are controlled by reversible
      binding to specific calcium-binding proteins. The calcium and magnesium flux
      across the external membrane is regulated by a calcium pump (calcium-magnesium
      ATPase), calcium channels, and binding to the membrane. In cell membranes and in
      lymphocytes of essential hypertensives our group showed increased calcium and a
      decreased magnesium and increased calcium/magnesium ratio in hypertensive cells.
      In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive
      rats (SHR) of the Munster strain (systolic blood pressure 188.4 +/- 9.8 mm Hg)
      and 13 normotensive rats (NT, systolic blood pressure 118.5 +/- 7.2 mm Hg) aged 9
      months, the intracellular calcium and magnesium contents were measured under
      nearly in vivo conditions by electron probe microanalysis. Measurements were
      performed in aortic cryosections 3 microm thick; the calcium content was 124.7 +/
      4.5 mmol/kg dry weight in SHR versus 110.3 +/- 4.1 mmol/kg dry weight in NT
      (mean +/- SD, P <.01 for both), the magnesium content was 35.5 +/- 3.9 in SHR
      versus 50.1 +/- 4.9 mmol/kg dry weight in NT (P <.01 for both). The
      calcium/magnesium ratio was significantly increased in SHR versus NT (3.56 +/-
      3.9 versus 2.23 +/- 0.27 [P <.01 for both]). Thus, aortic smooth muscle cells
      from SHR are characterized by a markedly elevated intracellular calcium and
      decreased intracellular magnesium contents compared with normotensive cells.
      Cellular calcium and magnesium handling is disturbed in SHR aortic smooth muscle
      cells as it is in hypertensive blood cells. The increased calcium/magnesium ratio
      in hypertensive cells is a pathogenetic factor for the development of
      arteriosclerosis and hypertension.

PMID- 14700515
TI  - Gene delivery of endothelial nitric oxide synthase into nucleus tractus solitarii
      induces biphasic response in cardiovascular functions of hypertensive rats.
AB  - BACKGROUND: Nitric oxide (NO) plays an important role in central control of blood
      pressure (BP). An intrinsic defect in NO availability in brain nucleus
      contributes to the elevated BP in the spontaneously hypertensive rats (SHR). This
      study was aimed to investigate the effect of endothelial NO synthase (eNOS) gene
      delivery in the nucleus tractus solitarii (NTS) on the cardiovascular functions
      of SHR. METHODS: Adenovirus vectors encoding either eNOS (Ad-eNOS) or green
      fluorescent protein (Ad-GFP) were used for gene transfer study. The
      cardiovascular functions in SHR received NTS gene delivery that were monitored by
      an oscillometric device. RESULTS: Infection of neuronal cells with Ad-eNOS
      increased the nitrite production but decreased the level of superoxide anion
      (O(2)(-)), indicating that eNOS gene delivery increased NO availability. After
      microinjection into NTS, adenovirus-mediated GFP or eNOS expression was confirmed
      by fluorescence microscopy and immunohistochemical analysis. On days 3 to 14
      after injection, a significant decrease in mean BP (MBP and heart rate (HR) was
      observed in Ad-eNOS-treated SHR, but not in Ad-GFP- or saline-treated SHR. Within
      this period, microinjection of the soluble guanylate cyclase inhibitor
      significantly reversed the Ad-eNOS-mediated depressor effect. However, on days 24
      to 40, the MBP of Ad-eNOS-treated animals escalated, then returned to the normal
      range after day 50. The mechanism underlying the rebound of BP in Ad-eNOS
      injected SHR remains to be elucidated. CONCLUSIONS: Intra-NTS eNOS gene delivery
      causes a depressor response in SHR, but a transient increase in MBP was observed
      after the Ad-eNOS-induced hypotension disappeared.

PMID- 14700516
TI  - Allylmercaptocaptopril: a new antihypertensive drug.
AB  - Allylmercaptocaptopril (CPSSA) was synthesized by reacting captopril with pure
      allicin. Fructose-induced hypertensive groups of rats were fed a fructose-rich
      diet for 3 weeks, and then received the diet plus either CPSSA (40 to 56 mg or
      138 to 194 micromol/L/kg/d) or captopril (80 mg or 369 micromol/L/kg/d) for 2
      more weeks. CPSSA (both doses) significantly lowered blood pressure (BP) from
      153.4 to 120.8 mm Hg (P <.005). Captopril gave similar results, lowering BP from
      150.7 to 123 mm Hg (P <.005). CPSSA also decreased the high levels of
      triglycerides to normal. The new stable compound allylmercaptocaptopril combines
      the beneficial properties of captopril and allicin and is a potential candidate
      for antihypertensive drug therapy.

PMID- 14700517
TI  - Plasma adrenomedullin and obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. The
      vasorelaxing peptide adrenomedullin (ADM) may counteract effects of OSA-induced
      release of vasopressor substances. METHODS: Plasma ADM levels were measured at
      9:30 PM, 2:00 AM (after 4 to 5 h of untreated OSA), and 6:00 AM (after 4 h of
      continuous positive airway pressure treatment) in 15 OSA patients and in 10
      controls. RESULTS: Baseline ADM levels were similar in the OSA and control groups
      (28.7 +/- 6.7 v 27.7 +/- 6.4 pg/mL, respectively), did not change overnight in
      either group, and were not affected by continuous positive airway pressure.
      CONCLUSIONS: OSA does not exert any significant acute or chronic effects on
      plasma ADM levels.

PMID- 14700518
TI  - Effect of valsartan and atenolol on sexual behavior in hypertensive
      postmenopausal women.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of valsartan
      compared with atenolol on sexual behavior in hypertensive postmenopausal women.
      METHODS: A total of 120 postmenopausal women, aged 51 to 55 years, with mild to
      moderate hypertension (diastolic blood pressure [DBP] >/=95 and </=105 mm Hg)
      were enrolled. After a 4-week placebo period they were randomized to treatment
      with valsartan 80 mg (n = 60) or atenolol 50 mg (n = 60) once daily for 16 weeks,
      according to a parallel arm design. After 4 weeks of treatment the nonresponder
      patients (DBP >90 mm Hg) were given a double dose of each drug. Patients were
      checked at the end of the placebo period and every 4 weeks thereafter. At each
      visit, sitting blood pressure (BP) was measured by mercury sphygmomanometer
      (Korotkoff I and V). At baseline and after 16 weeks of treatment, patients were
      given a questionnaire that comprised 10 self-evaluations of various aspects of
      sexual desire, orgasmic response, and coital activity. The questions were
      presented in the form of a visual analog scale. RESULTS: Both drugs significantly
      lowered BP without any difference between the two treatments. In the valsartan
      treated women, the scores for three of the items related to libido significantly
      improved: sexual desire (+38%, P <.01), changes in behavior (+45%, P <.001), and
      sexual fantasies (+51%, P <.001) In contrast, in the atenolol-treated group the
      scores for the items "sexual desire" and "sexual fantasies" significantly
      worsened (-18%, P <.01 and -23%, P <.001, respectively). CONCLUSIONS: These
      results suggest that in postmenopausal, sexually active hypertensive women,
      valsartan treatment improved sexual function at least in some respects, whereas
      atenolol worsened it. This may be relevant for quality of life in these patients
      and their compliance with antihypertensive therapy.

PMID- 14700519
TI  - Hypertension in women.
AB  - Essential hypertension presents itself differently in men and women. Before the
      menopause, there are obvious hormonal differences between the sexes and it is now
      known that after the menopause, the arterial tree ages differently. At all ages,
      the shorter stature in women and the obligatory shorter arterial tree induce
      faster heart rates and earlier reflected arterial pulse waves. These factors
      operate to influence systolic blood pressure (BP), pulse pressure (PP), PP
      amplification, diastolic time, and diastolic BP. The circulatory effects of these
      variables in youth and with aging help to explain the time dependent and aging
      differences in cardiovascular risk between men and women. The development of left
      ventricular hypertrophy, isolated systolic hypertension, and the complications
      after acute myocardial infarction are also explicable in part by these gender
      specific hemodynamic factors. Gender differences are also demonstrable in
      epidemiologic studies. Although an increased systolic BP is a cardiovascular risk
      in both sexes, a U-shaped curve describes the diastolic BP risk relationship in
      men but not in women. There is also a difference in the response to
      antihypertensive therapy, with a lesser benefit for women in heart disease
      prevention. These findings raise many remaining unanswered questions. Do some
      antihypertensive agents have gender-specific effects? Are the dose-response
      curves different for individual drugs or drugs in combination? Should therapeutic
      targets for systolic BP, diastolic BP, or PP differ between the sexes? Future
      answers to such questions would reduce the therapeutic trial and error now
      necessary for the selection of an individual patient's antihypertensive regimen.

PMID- 14700520
TI  - Estimated healthcare savings associated with adequate dairy food intake.
AB  - Medical literature that has coalesced during the past two to three decades has
      identified adequate intake of nutrients from dairy foods as a common factor in
      the reduction of the disease burden of several common medical conditions. These
      include obesity, hypertension, type 2 diabetes, osteoporosis, kidney stones,
      certain outcomes of pregnancy, and some cancers. Treatment of these disorders,
      particularly cardiovascular, consumes a significant portion of the United States'
      healthcare budget. Drawing on accumulated data from prospective longitudinal
      studies and randomized controlled trials, this article summarizes the evidence of
      the net benefits of increased dairy food intake on these conditions, their
      outcomes, and their costs. Estimated improvements in outcomes were combined with
      available data on annual costs of the respective disorders. From the calculated
      annual impact, we generated first-year and fifth-year healthcare cost savings
      that would accrue if adult Americans simply increased their intake of dairy foods
      to the currently recommended 3 to 4 servings/d. Using conservative estimates of
      potential benefit, we project first-year savings of approximately 26 billion
      dollars and 5-year cumulative savings in excess of 200 billion dollars.

PMID- 14700521
TI  - Adrenergic receptors in hypertension and heart failure.

PMID- 14700522
TI  - Paroxysmal hypertension during micturition.

PMID- 14700524
TI  - Mixture additives inhibit the dermal permeation of the fatty acid, ricinoleic
      acid.
AB  - Ricinoleic acid (RA) like many of the ingredients in machine cutting fluids and
      other industrial formulations are potential dermal irritants, yet very little is
      known about its permeability in skin. 3H-ricinoleic acid mixtures were formulated
      with three commonly used cutting fluid additives; namely, triazine (TRI), linear
      alkylbenzene sulfonate (LAS), and triethanolamine (TEA) and topically applied to
      inert silastic membranes and porcine skin in vitro as aqueous mineral oil (MO) or
      polyethylene glycol (PEG) mixtures. These additives significantly decreased
      ricinoleic acid partitioning from the formulation into the stratum corneum (SC)
      in PEG-based mixtures. Except for LAS, all other additives produced a more basic
      formulation (pH = 9.3-10.3). In silastic membranes and porcine skin, individual
      additives or combination of additives significantly reduced ricinoleic
      permeability. This trend in ricinoleic acid disposition in both membranes
      suggests that the mixture interaction is more physicochemical in nature and
      probably not related to the chemical-induced changes in the biological membrane
      as may be assumed with topical exposures to potentially irritant formulations.

PMID- 14700523
TI  - Lipopolysaccharide enhancement of 12-o-tetradecanoylphorbol 13-acetate-mediated
      transformation in rat glioma C6, accompanied by induction of inducible nitric
      oxide synthase.
AB  - Lipopolysaccharide (LPS) from Gram-negative bacterial has been identified as an
      important molecule involved in the inflammatory process through inducing nitric
      oxide (NO) production. However, the effect of LPS in carcinogenesis is still
      undefined. In the present study, the biological effect of LPS was examined in 12
      o-tetradecanoylphorbol 13-acetate (TPA)-treated rat glioma cells C6. Results of
      MTT assay showed that LPS and TPA exhibited no significant cytotoxicity in glioma
      C6 cells. Interestingly, transformation foci were found in LPS/TPA-treated glioma
      C6 cells, but not in LPS- or TPA-treated cells. The transformation foci induced
      by LPS/TPA were also observed in the absence of serum. It indicates that
      induction of transformation foci formation by LPS and TPA is independent on the
      serum in glioma C6 cells. Induction of iNOS gene expression and NO production was
      examined in LPS/TPA-treated cells, but not obvious in LPS- or TPA-treated cells.
      NO donor sodium nitroprusside (SNP) induces transformation in glioma C6 cells in
      according with elevating NO production. In addition, LPS/TPA induces
      metalloproteinase 9 (MMP9) activity by gelatin activity assay in gel. Wogonin and
      quercetin but not rutin, inhibitors of iNOS gene expression and NO production
      induced by LPS, showed the significant inhibition on LPS/TPA-induced
      transformation foci formation, accompanied by inhibiting iNOS gene expression, NO
      production and MMP9 activity. Results of the present study provide scientific
      evidences to link the inflammatory responses and carcinogenesis, and suggest that
      NO derived from inflammation may contribute to the progression of carcinogenesis;
      natural products with anti-inflammatory effects such as wogonin and quercetin
      possess the ability to block transformation induced by LPS/TPA.

PMID- 14700525
TI  - Impact of nitrate intake in drinking water on the thyroid gland activity in male
      rat.
AB  - The purpose of this study was to determine the effects of nitrate on both the
      activity of the thyroid gland and other biological parameters. After 5-month
      treatment, nitrate 150 and 500 mg/l induced a significant decrease in the serum
      level of thyroid hormone T3. For T4, the 500 mg/l dose only reduced its plasma
      level. On the other hand, nitrate induced a dose-dependent increase in the weight
      of the thyroid gland. The histological study of the thyroid gland shows
      vacuolisation and an increase in the size of the follicles accompanied by a
      flatness of follicular epithelium with nitrate 150 and 500 mg/l. We concluded
      that the presence of high concentrations of nitrate in drinking water influence
      the growth, induce morpho-functional modifications of the thyroid gland and might
      be considered as a goitrigenic factor.

PMID- 14700526
TI  - Synergistic DNA damage by oxidative stress (induced by H2O2) and nongenotoxic
      environmental chemicals in human fibroblasts.
AB  - Genotoxic combination effects of oxidative stress (induced by H2O2) and eight
      nongenotoxic environmental chemicals (4-chloroaniline, 2,3,4,6-tetrachlorophenol,
      lindane, 2,4-dichloroacetic acid (2,4-D), m-xylene, glyphosate, nitrilotriacetic
      acid and n-hexanol) were determined in human fibroblasts. Genotoxicity was
      measured quantitatively by the single cell gel electrophoresis assay. The
      nongenotoxic chemicals were used in non cytotoxic concentrations. H2O2 was used
      in concentrations producing low (50 microM) and no cytotoxicity (40 microM). All
      environmental chemicals acted in a synergistic way with H2O2 except DMSO which
      effectively inhibited H2O(2)-induced DNA damage. The most effective enhancers
      were 4-chloroaniline, 2,3,4,6-tetrachlorophenol, m-xylene, and n-hexanol.
      Synergistic effects of hexanol/H2O2 were still evident at a concentration of 0.09
      noec (no observed effect concentration). In contrast to synergistic DNA damage in
      the cell antagonism was found measuring DNA breakage in isolated PM2 DNA. From
      the results we concluded that synergisms between H2O2 and nongenotoxic chemicals
      may be a general phenomenon which is not observed on the level of isolated DNA.

PMID- 14700527
TI  - Effects of hydrogen peroxide on sodium current in acutely isolated rat
      hippocampal CA1 neurons.
AB  - The effects of hydrogen peroxide (H2O2) on sodium currents (Na+ currents) in
      freshly dissociated rat hippocampal neurons were studied using the whole-cell
      patch-clamp techniques. H2O2 caused a reversible increase of the voltage
      activated Na+ currents in a concentration- and voltage-dependent manner. The half
      increasing concentration (EC50) of H2O2 on Na+ currents was 10.79 microM. In
      addition, 10 microM H2O2 shifted the steady-state inactivation curve of Na+
      currents toward positive potential (control Vh = -64.58 +/- 1.22 mV, H2O2 Vh = 
      53.55 +/- 0.94 mV, n = 10, P < 0.01 without changing the slope factor). However,
      the steady-state activation curve was not affected. These results indicated that
      H2O2 could increase the amplitudes of Na+ currents and change the inactivation
      properties of Na+ channels even in very low concentration.

PMID- 14700528
TI  - Methyl parathion interaction with human and bovine serum albumin.
AB  - Methyl parathion (MP; O,O-dimethyl O-p-nitrophenyl phosphorothioate) is an
      organophosphorous compound still largely used in agriculture and fish hatcheries.
      This pesticide is not quite selective and is potentially toxic for both
      vertebrates and invertebrates. Its mechanism of acute toxicity is the inhibition
      of the enzyme acetylcholinesterase in nervous tissue. Binding of pesticides to
      plasma proteins is one of many factors that influence their distribution and
      elimination. The free concentration available for toxic action can be effectively
      reduced for pesticides with high binding to plasma proteins, although the
      affinity of pesticides to plasma proteins is often lower than for the enzyme
      targets. Several different transport proteins exist in blood plasma, but albumin
      only is able to bind a wide diversity of xenobiotics reversibly with high
      affinity. It was already known that parathion (ethyl parathion) exhibits a high
      affinity to human and bovine serum albumins. We studied interactions of methyl
      parathion with these albumins by using fluorescence quenching techniques. We
      selectively excited the fluorescence of tryptophan residues with a 290 nm
      wavelength light, and observed quenching by titrating human and bovine serum
      albumin solutions with methyl parathion. Stern-Volmer graphs were plotted and
      quenching constants were estimated. Our results pointed to the formation of
      complexes of methyl parathion with albumins. Association constants at 25 degrees
      C were 3.07 x 10(4) (1.2 x 10(3))M(-1) for human serum albumin, and 1.96 x 10(4)
      (+/- 4.5 x 10(2))M(-1) for bovine serum albumin. At 37 degrees C, they were 1.08
      x 10(4) (+/- 2.0 x 10(2))M(-1) for human serum albumin, and 8.16 x 10(3) (+/- 1.9
      x 10(2))M(-1) for bovine serum albumin. Results also suggest that the primary
      binding site for methyl parathion on albumin is close to tryptophan residues 214
      of human serum albumin and 212 of bovine serum albumin.

PMID- 14700529
TI  - The neurotoxicant trimethyltin induces apoptosis via caspase activation, p38
      protein kinase, and oxidative stress in PC12 cells.
AB  - Acute exposure to trimethyltin (TMT) causes neuronal degeneration in the
      hippocampus, amygdala, pyriform cortex, and neocortex [Am. J. Pathol. 97 (1979)
      59]. Despite extensive efforts elucidating neuropathological changes and
      behavioral deficits following TMT exposure, only a limited amount of work has
      examined the molecular signaling mechanisms that lead to these changes. The
      present paper demonstrates that TMT impairs neurite outgrowth and cell viability
      in an in vitro model of neuronal development. The decrease in cell viability is
      paralleled by a decrease in cell body size, an increase in DNA fragmentation,
      activation of caspase-9, and cleavage of the caspase substrate poly-ADP ribose
      polymerase (PARP). These results suggest that TMT induces apoptosis.
      Pharmacological inhibition of caspase activity, p38 stress-responsive protein
      kinase activity, or oxidative stress prevented TMT-induced cell death. This work
      provides the first evidence for a TMT-initiated apoptotic pathway requiring
      oxidative stress, caspase activation, and p38 protein kinase activity.

PMID- 14700530
TI  - The investigation of the genotoxic effects of fenarimol and propamocarb in mouse
      bone marrow in vivo.
AB  - In this study, we aimed to evaluate the genotoxic effects of fungicides fenarimol
      and propamocarb which are used to protect crops from fungi. For this reason, bone
      marrow micronucleus and chromosome aberration tests were carried out in Swiss
      albino mice. Mice were injected with four different doses of fenarimol and
      propamocarb intraperitoneally; 50, 100, 200 and 400 mg/kg b.w. Fenarimol did not
      induce any significant increase in micronucleated erythrocytes after 24, 36, and
      48 h treatment but it decreased the ratio of polychromatic/normochromatic
      erythrocytes at all dose groups and sampling intervals. Fenarimol did not
      increase the number of chromosome aberrations significantly, but it reduced the
      mitotic index at the higher doses (P < 0.05). Propamocarb did not increase the
      frequency of micronucleated erythrocytes, but decreased the
      polychromatic/normochromatic erythrocytes ratio at all sampling intervals.
      Propamocarb increased only gaps in total chromosome aberrations, but when gaps
      were excluded, there were no significant differences in total aberrations between
      the control and dose groups (P > 0.05). Propamocarb also reduced the mitotic
      index compared with the negative control group (P < 0.001). Contributing these
      results, we can suggest that fenarimol and propamocarb are non-genotoxic in mouse
      bone marrow in vivo but have cytotoxic effects.

PMID- 14700531
TI  - Induction of oxidative stress in murine cell lines by 3-chloro-4-(dichloromethyl)
      5-hydroxy-2(5H)-furanone (MX).
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the potent bacterial
      mutagen produced during chlorination of drinking water, was tested for the
      induction of oxidative stress in two murine cell lines: NIH 3T3 (fibroblasts) and
      L929 (fibrosarcoma cells). Following 1 h MX treatment at concentrations between
      100 and 1000 microM, cellular stress conditions were monitored by measuring
      reactive oxygen species formation (ROS) and reduced glutathione levels (GSH). The
      kinetics of ROS formation and GSH depletion was investigated from 10 min to 1 h.
      MX caused detachment of cells at 1000 microM in L929 cells and at 300 microM in
      NIH 3T3 cells but the viability of the cells, measured by the trypan blue assay,
      decreased only by 20 and 7%, respectively, in 1h. MX increased ROS production in
      L929 cells in a dose-dependent manner, by 120% at 500 microM of MX in 1 h. The
      maximum ROS production was attained already in 10min. In NIH 3T3 cells, the ROS
      production was slightly, but not statistically significantly stimulated at 200
      microM between 20 and 60 min. Concomitantly, MX decreased the intracellular
      content of GSH dose-dependently in both cell lines, by 48% in L929 cells at 500
      microM of MX and 32% in NIH 3T3 cells at 200 microM of MX in one hour. The
      majority of this GSH depletion had occurred in 10 min. These findings indicate
      that MX induces oxidative stress in mammalian cells in vitro though the
      sensitivity of cells may differ for this effect.

PMID- 14700532
TI  - Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain
      neurotransmitter levels without concurrent inhibition of the brain sphingolipid
      biosynthesis in mice.
AB  - Myriocin is a specific serine palmitoyltransferase (SPT) inhibitor whose effect
      on the brain is unknown. Brain amine metabolism and sphingolipid biosynthesis
      were studied in mice treated intraperitoneally with 0, 0.1, 0.3 or 1 mg/kg per
      day of myriocin for 5 days. Regional concentrations of dopamine (DA), 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine
      (5-HT, serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE),
      were determined. Sphinganine (Sa) and sphingosine (So) concentrations and SPT
      activity in brain and liver were used to evaluate the impact of myriocin on
      sphingolipid biosynthesis. Myriocin treatment increased DA in striatum and
      hippocampus and reduced it in cortex. NE concentration decreased in cerebellum
      and 5-HT levels were reduced in cortex and in medulla oblongata. Changes in
      ratios for DOPAC/DA and HVA/DA were observed in hippocampus, cortex and midbrain.
      Brain Sa, So and SPT activity remained unchanged, whereas Sa and SPT activity
      decreased in liver. Results showed that myriocin may alter the levels and
      metabolism of brain amines and this effect is not related with inhibition of
      sphingolipid biosynthesis in the nervous system.

PMID- 14700533
TI  - FDC-B1: a new monoclonal antibody directed against bovine follicular dendritic
      cells.
AB  - Follicular dendritic cells (FDCs) are a unique population of accessory cells
      located in the light zone of the germinal centres of lymphoid follicles. Their
      involvement in the generation of humoral immune responses implies a potential
      role for these cells in many disorders. Indeed, in prion diseases, FDCs seem to
      be the major sites of extraneuronal cellular prion protein expression and the
      principal sites of the infectious agent accumulation in lymphoid organs. The
      identification of FDC is useful for the analysis of their distribution in
      reactive lymphoid tissue as well as in pathological conditions. The production
      and characterisation of a new mouse monoclonal antibody directed against bovine
      follicular dendritic cells (FDC-B1) is reported. The antigen detected by FDC-B1
      is expressed exclusively on the surface of FDCs in ruminant lymphoid organs. The
      antigen has an approximate molecular weight of 28 kDa.

PMID- 14700534
TI  - Development of a new monoclonal antibody to ovine chimeric IgE and its detection
      of systemic and local IgE antibody responses to the intestinal nematode
      Trichostrongylus colubriformis.
AB  - The J558L cell line, previously transfected with the ovine Cepsilon gene, was
      induced to secrete a chimeric IgE protein composed of the ovine heavy chain and a
      mouse light chain with MW of approximately 80 and 26 kDa, respectively. After
      purification, the chimeric protein was used to immunise BALB-c mice and
      monoclonal antibodies (mAbs) were generated. The mAb 2F1, which had greatest anti
      IgE activity in preliminary screens, was chosen for further characterisation and
      an examination of systemic and local IgE responses to the intestinal nematode,
      Trichostrongylus colubriformis. The chimeric IgE protein was not recognised in
      enzyme linked immunosorbent assay (ELISA) by mAbs raised against ovine IgG1,
      IgG2, IgA or IgM. However, 2F1 was highly specific to the chimeric IgE protein,
      and did not cross-react with ovine IgG1, IgG2 or IgA. Western blot analysis also
      showed that 2F1 and secretory IgA (sIgA) did not cross-react, and that 2F1 and
      the anti-IgA mAb identified different MW bands from colostrum (approximately 200
      and 400 kDa, respectively). 2F1 bound to mucosal mast cells (MMC) isolated from
      the intestines of lambs infected with T. colubriformis, but cultured bone marrow
      derived mast cells (BMMC) required prior incubation with the chimeric IgE protein
      for this binding to occur. Distinctive staining of plasma cells and putative mast
      cells were observed using 2F1 on immunohistological sections of mesenteric lymph
      node and jejunum.ELISA incorporating 2F1 was able to detect >0.4 ng chimeric
      protein. Total IgE in ovine colostrum and intestinal homogenates was quantified
      using a capture ELISA, with known amounts of chimeric protein used to produce a
      standard curve. Colostrum from outbred Merino ewes had 0.55-11.05 ng ml(-1) total
      IgE, and their lambs, at necropsy after infection with a total of 18,000 T.
      colubriformis infective larvae over a 9-week period, had 45-620 ng g(-1) total
      IgE in intestinal tissue. Compared to genetically susceptible lambs, antigen
      specific levels of IgE were significantly higher in genetically resistant lambs
      after infection with 4500 T. colubriformis infective larvae (TcL3) per week for 9
      weeks (161.4 versus 44.8 geometric mean titres; P=0.043). In western blots,
      distinctive bands (19-21 and 27 kDa) from T. colubriformis larval antigen were
      differentially recognised by IgE, as identified by 2F1, in intestinal homogenates
      from genetically resistant animals. These results have demonstrated the value of
      2F1 for quantification of IgE responses in samples derived from ovine fluids and
      tissues using ELISA, western blots and immunohistology. In this respect, it
      recognises native ovine IgE and does not require pre-treatment of the sample with
      denaturing agents or ammonium sulphate.

PMID- 14700535
TI  - Apoptosis and proliferative activity in lymph node reaction in postweaning
      multisystemic wasting syndrome (PMWS).
AB  - Postweaning multisystemic wasting syndrome (PMWS) affects nursery and growing
      pigs, and is characterized by wasting, failure to thrive, pale skin, respiratory
      distress, diarrhoea and sometimes jaundice. Macroscopic findings are aspecific,
      but lymphocyte depletion in lymphoid tissues is one of the histological hallmarks
      [Vet. Q. 24 (2002) 109]. Spontaneous cases of PMWS were studied to evaluate
      proliferative activity and apoptosis as mechanisms involved in the pathogenesis
      of cell depletion in lymph nodes. The presence of Porcine Circovirus type 2
      (PCV2) genome in the processed material was confirmed by in situ hybridization
      (ISH). The lymph node pattern of depletion was graded as initial, intermediate or
      final stage according to histological criteria in 10 superficial inguinal nodes
      from piglets with PMWS which died spontaneously or were slaughtered by
      euthanasia. The apoptotic and proliferative fraction were investigated by
      monoclonal antibody MIB1 immunohistochemistry and TUNEL (terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-nick end labeling) methods,
      respectively, and compared to three normal cases. One-way analysis of variance
      (ANOVA) comparison between the MIB1 index (number of positive cells per 100
      nuclei) in controls and PMWS cases revealed a decrease of proliferation in both
      lymphoid and medulla-like tissues in the initial group (respectively, P=0.0017
      and 0.024) but not in the intermediate (respectively, P=0.25 and 0.88) or final
      (respectively, P=0.47 and 0.81) cohorts. The apoptotic index (number of
      apoptosis/apoptotic bodies in 100 cells) revealed a statistically significant
      decrease only in the initial group (one-way ANOVA P=0.05). The
      proliferation/apoptosis ratio (MIB1/APO ratio) assessed to determine cell
      turnover disclosed a significant decrease of cell turnover from initial to final
      PMWS cases (Spearman's rank test: P=0.027). Decreased cell proliferation and not
      increased apoptosis seems to be the most important variable leading to cell
      depletion in PMWS lymphoid tissues.

PMID- 14700536
TI  - Cloning of porcine scFv antibodies by phage display and expression in Escherichia
      coli.
AB  - Oligonucleotide primers were designed for recovery of Ig H, kappa and lambda
      transcripts from porcine splenic cDNA. The products were cloned and scFvs
      constructed in a phage display vector. E. coli HB2151 was transformed with the
      constructs and upon induction, scFvs of the predicted molecular weight could be
      detected in culture supernatants by Western blotting and immunoprecipitation with
      anti-pig IgG. Bacteriophage displaying a swine scFv were diluted into an excess
      of phage carrying a human anti-thyroglobulin scFv and then panned on plastic
      coated with anti-pig IgG. Rapid enrichment of phage carrying the porcine scFv
      through three rounds of selection demonstrated the successful display of an
      authentically folded pig Ig at the viral surface. The data demonstrate that phage
      display techniques can be applied successfully to porcine Igs and that expression
      of recombinant pig scFvs in bacteria can be achieved. These techniques offer the
      opportunity to generate authentic porcine monoclonal reagents for basic and
      applied studies.

PMID- 14700537
TI  - Expression of interleukin 4, interleukin 4 splice variants and interferon gamma
      mRNA in calves experimentally infected with Fasciola hepatica.
AB  - Interleukin 4 (IL-4) is expected to play a dominant role in the development of T
      helper (Th) 2 cells. Th2 immune responses with expression of relatively large
      amounts of interleukin 4 (IL-4) but little interferon gamma (IFN-gamma) are
      characteristic for chronic helminth infections. But no information is available
      about IL4 expression during early Fasciola hepatica (F. hepatica) infections in
      cattle. Therefore, we investigated F. hepatica specific IL-4 and IFN-gamma mRNA
      expression in peripheral blood mononuclear cells (PBMCs) from calves
      experimentally infected with F. hepatica. Cells were collected prior to infection
      and on post-inoculation days (PIDs) 10, 28 and 70. Interestingly, PBMCs responded
      to stimulation with F. hepatica secretory-excretory products (FhSEP) already on
      PID 10 and expressed high amounts of IL-4 but not of IFN-gamma mRNA suggesting
      that F. hepatica induced a Th2 biased early immune response which was not
      restricted to the site of infection. Later in infection IL-4 mRNA expression
      decreased whereas IFN-gamma mRNA expression increased slightly. Isolated lymph
      node cells (LNCs) stimulated with FhSEP and, even more importantly, non
      stimulated LN tissue samples indicated highly polarized Th2 type immune responses
      in the draining (hepatic) lymph node, but not in the retropharyngeal lymph node.
      During preliminary experiments, two splice variants of bovine IL-4 mRNA, boIL
      4delta2 and boIL-4delta3, were detected. Since a human IL-4delta2 was assumed to
      act as competitive inhibitor of IL-4, it was important to know whether expression
      of these splice variants of bovine IL-4 have a regulatory function during an
      immune response to infection with F. hepatica. Indeed, IL-4 splice variants could
      be detected in a number of samples, but quantitative analysis did not yield any
      clue to their function. Therefore, the significance of bovine IL-4 splice
      variants remains to be determined.

PMID- 14700538
TI  - Generation and characterisation of an equine macrophage cell line (e-CAS cells)
      derived from equine bone marrow cells.
AB  - Macrophages play a pivotal role in the pathophysiology of many diseases by
      mediating the host immune response to infections and intoxications. The species
      specific activation of macrophages and the differential response in cytokine
      production impedes the extrapolation of results between species. Therefore, the
      aim of this study was to isolate and immortalise macrophages from equine bone
      marrow (BM) cells in order to study equine-specific signalling pathways. The
      isolated BM-derived macrophages (referred to as e-CAS cells) showed proliferation
      kinetics similar to that of standardised cell lines and were maintained in
      culture for >76 passages. To characterise the cells, a number of typical
      parameters of macrophages were tested. Morphological evaluation (May-Grunwald
      Giemsa staining) and non-specific esterase activity indicated the e-CAS cells to
      be macrophages. The presence of CD14 and their ability to phagocytose Escherichia
      coli bioparticles further confirmed their identity, as did their ability to
      produce cytokines, reactive oxygen and nitrogen intermediates in response to LPS.
      These data show that the established cell line (e-CAS) shows the characteristics
      of equine macrophages and may, therefore, prove to be a unique in vitro model for
      studying the cellular biology of equine inflammation.

PMID- 14700539
TI  - Effect of age on immune parameters and the immune response of dogs to vaccines: a
      cross-sectional study.
AB  - The evaluation of anti-aging intervention strategies in dogs would benefit from
      reliable quantitative biomarkers of aging. In the present study, the expression
      of various immune parameters was measured in young and old dogs to identify
      potential biomarkers of aging. The second goal of the study was to determine the
      effect of age on the immune response to vaccines. The immune function, including
      the antibody response to vaccines, was determined in 32 young adult (3.15+/-0.8
      years of age) and 33 old dogs (12.1+/-1.3 years of age) of various breeds. Old
      dogs had a significantly lower lymphocyte proliferative response and a lower
      percentage of CD4+ T cells and CD45R+/CD4+ T cells, and a higher percentage of
      CD8+ T cells and a higher concentration of serum and salivary IgA. The most
      significant differences (P<0.001) occurred in the lymphocyte proliferative
      responses to ConA and PHA, the CD4:CD8 ratio, and the percentage of CD45R+/CD4+ T
      cells suggesting that these parameters are potential biomarkers of aging. There
      was no difference in the percentage of total T and B lymphocytes and the
      concentration of serum IgM and IgG. Both groups of dogs had protective titers
      against distemper virus, parvovirus and rabies virus before annual revaccination.
      The pre-vaccination titer against rabies virus was higher in the old dogs than in
      the young dogs, and there were no differences in post-vaccination titers against
      any of the viruses. This suggests that annual vaccination protocols provide
      adequate protection for old dogs.

PMID- 14700540
TI  - IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine
      heaves.
AB  - Heaves is a common condition of horses of cold climate that is characterized by
      small airway inflammation and obstruction following exposure of susceptible
      horses to moldy hay and straw. It has been shown that helper T lymphocytes (Th)
      orchestrate the inflammatory response in asthma and in various animal models of
      allergic lung diseases by the release of Th2-type cytokines. Results of previous
      studies indicate that a predominant expression of Th2-type response by airway
      cells may also be present in heaves. To evaluate the temporal mRNA expression of
      Th1 (IFN-gamma) and Th2 (IL-4, IL-5) type cytokines in heaves and their
      relationship to clinical disease, we studied the pulmonary mechanics and cytokine
      mRNA expression (IL-4, IL-5 and IFN-gamma) in bronchoalveolar lavage lymphocytes
      of horses with heaves (n=6) and control (n=6) before and after 24h and 9 days of
      continuous natural inhalation challenge. Starting 24h after challenge horses with
      heaves, but not control horses, had a significant increase in pulmonary elastance
      and the number of lymphocytes expressing mRNA for IL-4 and IL-5. These changes
      were further increased at 9 days, at which time the number of cells positive for
      IFN-gamma mRNA was decreased. In this study we have shown that BAL lymphocytes of
      horses with heaves during clinical exacerbation have a predominant Th2-type
      cytokine response and that this response coincides in time with the presence of
      airway obstruction.

PMID- 14700541
TI  - Immunization of rats against Fasciola hepatica using crude antigens conjugated
      with Freund's adjuvant or oligodeoxynucleotides.
AB  - Chronic Fasciola hepatica infection is correlated with the development of a T
      helper (Th2)-predominant immune response. To determine whether immunostimulatory
      CpG-containing oligodeoxynucleotides (CpG-ODN) or Freund's complete adjuvant
      (FCA), known to promote a Th1 (T helper 1) immune responses, could provide
      protection from F. hepatica infection, total homogenate (TH) of F. hepatica mixed
      with CpG-ODN or FCA were injected subcutaneously (s.c.) into Wistar rats. A F.
      hepatica-specific Th1-predominant immune response was induced with CpG-ODN or FCA
      in lymph nodes of immunized animals. Lymph node cells from TH-CpG-ODN or TH-FCA
      immunized rats showed increased antigen-specific proliferation with high levels
      of INFgamma, compared to lymphocytes from rats injected with TH alone. In
      contrast, these two groups of immunized animals did not modify IL-4 release by
      draining lymph node cells, when they were subsequently stimulated with TH in
      vitro. However, a significant reduction in the burden of flukes (76.7%) was only
      observed in rats immunized with TH-FCA. Conversely, immunization of rats with TH
      CpG-ODN did not promote protection against the parasite. Therefore, even though
      CpG-ODNs and FCA induced Th1 type responses, only FCA provided a significant
      protection to rats infected with F. hepatica.

PMID- 14700542
TI  - Repeatability of flow cytometric and classical measurement of phagocytosis and
      respiratory burst in bovine polymorphonuclear leukocytes.
AB  - Five methods for measurement of phagocytosis and respiratory burst activity of
      bovine blood polymorphonuclear leukocytes (PMNs) were evaluated. Eight cows were
      repeatedly sampled over a two week period and parallel samples tested in all five
      assays to assess the repeatability and stability of the methods. In the flow
      cytometric phagocytosis assay, ingestion of fluorescein labeled bacteria was
      measured, and in the flow cytometric assay for respiratory burst, oxidation of a
      dye by reactive oxygen species was recorded. In the classical assays,
      bactericidal effect on opsonized, live bacteria was quantified by the conversion
      of an indicator substance, superoxide anion production was assayed by the
      reduction of cytochrome c, whereas myeloperoxidase activity was determined with a
      radioactive iodination assay. The results showed that the Phagotest, Bursttest,
      cytochrome c and iodination assays gave repeatable results when samples were run
      in the same setup on the same day. Although day-to-day variability was
      significant in all assays, the described methods comprise a panel of useful tests
      for the evaluation of phagocytosis and respiratory burst activity in bovine PMNs.
      The flow cytometric methods represent a convenient alternative to the classical
      methods for measurement of phagocytosis and respiratory burst in bovine blood
      PMNs.

PMID- 14700543
TI  - Transformation and DNA repair: linkage by DNA recombination.
AB  - The stability of microbial genomes is constantly challenged by horizontal gene
      transfer, recombination and DNA damage. Mechanisms for rapid genome variation,
      adaptation and maintenance are a necessity to ensure microbial fitness and
      survival in changing environments. Indeed, genome sequences reveal that most, if
      not all, bacterial species have numerous gene functions for DNA repair and
      recombination. These important topics were addressed at the Second Genome
      Maintenance Meeting (GMM2).

PMID- 14700544
TI  - Transporter's evolution and carbohydrate metabolic clusters.
AB  - The yiaQRS genes of Escherichia coli K-12 are involved in carbohydrate
      metabolism. Clustering of homologous genes was found throughout several unrelated
      bacteria. Strikingly, all four bacterial transport protein classes were found,
      conserving transport function but not mechanism. It appears that during evolution
      the ability to transport, phosphorylate and metabolize substrates of unknown
      identity have been conserved. However, the transporter classes have been swapped.
      This probably demonstrates the subtlety of transport-protein evolution.

PMID- 14700545
TI  - All things great and small.

PMID- 14700546
TI  - On the conceptual difficulties in rooting the tree of life.
AB  - Rooting the 'tree of life' represents a major challenge for evolutionists.
      Without such a root, many of the first steps in biological evolution cannot be
      reconstructed. However, the nature of the last common ancestor of all living
      beings remains elusive, proof of the difficulty in shedding light on such an
      ancient event. Here, we highlight the practical difficulties and conceptual
      reasons that hinder the placement of a universal root. We discuss how, when
      addressing the question of the root of the tree of life, scientists unconsciously
      risk using the reasoning pattern of ancient skeptics, unfortunately known only to
      lead to further uncertainty. Hence, we argue that the root of the tree of life
      will not be established unless radically new approaches are considered. We
      propose a hypothetical means to overcome several of the conceptual difficulties
      pointed out, and suggest that a so-called 'transition analysis' of the structural
      evolution of the cytoplasmic membrane might be helpful, especially if
      evolutionary steps involving the rooting issue are polarized accounting more for
      physicochemical knowledge rather than hypothetical and controversial selective
      advantages.

PMID- 14700547
TI  - Microbial endocrinology and infectious disease in the 21st century.
AB  - More than 70 years ago, a new age in endocrinology was just beginning with the
      first purification of a hormone, adrenaline. As early as 1930, almost immediately
      following its first use, cases of adrenaline-associated sepsis were reported.
      From this time, there have been reports associating the elaboration of
      neuroendocrine hormones, such as adrenaline, with infectious disease. The most
      widely accepted theory to explain the ability of hormones to influence the course
      of infection involves the suppression of the immune system. The theory that the
      infectious microorganism itself might be equally responsive to the host's
      neuroendocrine environment has not been considered. It is the intent of this
      article to introduce a new perspective to the current understanding of the
      factors that mediate the ability of bacteria to cause disease, and to demonstrate
      that neuroendocrinology and microbiology intersect to form the interdisciplinary
      field of microbial endocrinology.

PMID- 14700548
TI  - Message from a human gut symbiont: sensitivity is a prerequisite for sharing.
AB  - Microbial genome sequencing projects are beginning to provide insights about the
      molecular foundations of human-bacterial symbioses. The intestine contains our
      largest collection of symbionts, where members of Bacteroides comprise
      approximately 25% of the microbiota in adults. The recently defined proteome of a
      prominent human intestinal symbiont, Bacteroides thetaiotaomicron, contains an
      elaborate environmental-sensing apparatus. This apparatus includes an
      unprecedented number of extracytoplasmic function (ECF) sigma-factors, and a
      large collection of novel hybrid two-component systems composed of membrane
      spanning periplasmic proteins with histidine kinase, phosphoacceptor, response
      regulator receiver and DNA-binding domains. These sensors are linked to the
      organism's large repertoire of genes involved in acquiring and processing dietary
      polysaccharides ('the glycobiome'). This arrangement illustrates how a successful
      symbiont has evolved strategies for detecting and responding to conditions in its
      niche so that it can sustain beneficial relationships with its microbial and
      human partners.

PMID- 14700549
TI  - Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis.
AB  - Helicobacter pylori represents a highly successful human microbial pathogen that
      infects the stomach of more than half of the world's population. H. pylori
      induces gastric inflammation, and the diseases that can follow such infection
      include chronic gastritis, peptic ulcers and, more rarely, gastric cancer. The
      reasons why a minority of patients with H. pylori develops gastric cancer could
      be related to differences in host susceptibility, environmental factors and the
      genetic diversity of the organism. This review examines the features of H. pylori
      induced epithelial cell signalling in gastric diseases. Clinical studies and
      animal models, and also evidence for H. pylori strain-related differences in
      gastric epithelial cell proliferation in vivo are discussed. In addition, the
      mechanisms by which H. pylori triggers hyperproliferative processes and takes
      direct command of epithelial cell signalling, including activation of tyrosine
      kinase receptors, cell-cell interactions and cell motility are reviewed.

PMID- 14700550
TI  - Evolution of minimal-gene-sets in host-dependent bacteria.
AB  - Several attempts have been made to identify the minimal set of genes that is
      required for life using computational approaches or studies of deletion mutants.
      These experiments resemble those already performed by nature; a few hundred
      million years ago an ancestor of Escherichia coli was domesticated by aphids,
      which resulted in the elimination of 70-75% of the original bacterial genome.
      Amazingly, the small genomes of these imprisoned bacteria are more stable than
      those of their free-living relatives. Minimal-gene-sets that have evolved
      naturally are largely species-specific, with the exception of a small set of core
      genes that are required for information processing. Comparative genomics of host
      dependent bacteria have shown that minimal-gene-sets can persist in nature for
      tens of millions of years provided that the environment is rich in nutrients,
      that the host population size is large and that there is a strong host-level
      selection for bacterial gene functions.

PMID- 14700551
TI  - Toll-like receptors and innate antifungal responses.
AB  - The mammalian Toll-like receptors (TLRs) are homologues of Drosophila Toll and
      constitute a novel protein family involved in the mediation of innate immunity
      and the activation of adaptive immunity. Analysis of infection with human
      pathogenic fungi Candida albicans and Aspergillus fumigatus implicated TLR2 and
      TLR4 in elicitation of immune responses. Cryptococcus neoformans is recognized by
      a process that uses TLR4. C. albicans induces immunostimulation through causative
      agents, such as mannan or its structural derivatives (e.g. phospholipomannan),
      which are recognized by the immune system as pathogen-associated molecular
      patterns and are located in the cell wall of fungi. Secreted aspartic proteinases
      represent a key virulence factor that contributes to the ability of C. albicans
      to cause mucosal and disseminated infections, and might be a further potential
      stimulator of TLRs. Simultaneous activation of other pattern recognition
      receptors collaborating with TLRs illustrates the cooperation of various chains
      within ligand-specific receptor complexes for the recognition of fungal pathogens
      and their cell wall components.

PMID- 14700552
TI  - Endocrine and metabolic aspects of adult Prader-Willi syndrome with special
      emphasis on the effect of growth hormone treatment.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental
      retardation, short stature, abnormal body composition, muscular hypotonia and
      distinctive behavioural features. Excessive eating causes progressive obesity
      with increased cardiovascular morbidity and mortality. In the PWS genotype loss
      of one or more normally active paternal genes in region q11-13 on chromosome 15
      is seen. It is supposed that the genetic alteration leads to dysfunction of
      several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common.
      PWS is well described in children, in whom GH treatment improves body
      composition, linear growth, physical strength and agility. Few studies have
      focused on adults. We examined a cohort of 19 young adults with clinical PWS (13
      with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the
      GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values,
      low total IGF-I and in relation to the obesity low levels of free IGF-I and non
      suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral
      density (BMD) was low. Four patients had impaired glucose tolerance and nine
      patients high homeostasis model assessment (HOMA) index, indicating insulin
      resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the
      PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and
      8 women), subsequently completed a 12 months GH treatment trial, and GH had
      beneficial effects on body composition without significant adverse effects. The
      effects were more pronounced in the patients with the PWS genotype. Analysis of
      peptides involved in appetite regulation showed that leptin levels were high
      reflecting obesity and as a consequence NPY levels were low. In relation to the
      patients obesity circulating oxytocin levels were abnormally low and ghrelin
      levels abnormally high. Thus, oxytocin and ghrelin might be involved in the
      hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In
      conclusion this pilot study showed that adults with PWS have a partial GH
      deficiency, and GH treatment has beneficial effects on body composition in adult
      PWS without significant side-effects. Larger and longer term studies on the
      effect of GH replacement in adult PWS are encouraged.

PMID- 14700553
TI  - Clinical pharmacological aspects of growth hormone administration.

PMID- 14700554
TI  - Glucose metabolism and visceral fat in GH deficient adults: 1 year of GH
      replacement.
AB  - The aim of the current study is to evaluate the effects of 12-month growth
      hormone (GH) replacement on glucose metabolism and visceral fat in 24 adults with
      GH deficiency (11 men, 13 women, age 41+/-1.9 year, BMI 27+/-1.2 kg/m2. Glucose
      metabolism was measured in the fasting state by the homeostatic model assessment
      (HOMA) insulin resistance index and during a standard oral glucose tolerance test
      (OGTT). Data were analyzed by HOMA and the insulin sensitivity index (ISI)
      composite derived from the OGTT. Visceral fat was evaluated by CT scan. GH
      deficient adults had increased visceral fat (P=0.029) with lower fasting glucose
      levels (P=0.004) than the control group on baseline evaluation. GH replacement
      induced deterioration in glucose metabolism, with progressive increment in
      fasting insulin levels at 6 and 12 months (P=0.024) and in 2-h-OGTT insulin
      levels at 3, 6 and 12 months (P=0.001). Plasma glucose levels did not change
      during the study. There was a deterioration in insulin sensitivity index observed
      by an increase in HOMA-IR (P=0.049) and a reduction in the ISI-composite
      (P=0.028), both at 12 months of replacement. Visceral fat and waist-to-hip-ratio
      (WHR) reduced not only at month 6 but also at month 12 (P=0.0001 and 0.023,
      respectively). In conclusion, 12 months of GH replacement seem to impair glucose
      homeostasis, despite favorable alterations in body composition.

PMID- 14700555
TI  - Multiple signaling pathways are involved in the regulation of IGF-I receptor
      inhibition of PTEN-enhanced apoptosis.
AB  - PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3'
      position, thereby antagonizing PI3-kinase activity. A reduction in PI3' kinase
      activity enhances the susceptibility of cells to apoptosis. By stably
      transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein
      levels were reduced by approximately 50% and etoposide-induced apoptosis was
      markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic
      effect was inhibited by both PI3' kinase and by specific inhibitors of p38 MAP
      kinase. Thus, we show for the first time that p38 MAP kinase is involved in this
      process.

PMID- 14700557
TI  - Placental growth hormone during pregnancy in a growth hormone deficient woman
      with type 1 diabetes compared to a matching diabetic control group.
AB  - In pregnancy, pituitary growth hormone (GH) is gradually replaced by placental
      growth hormone (hPGH). GH deficient pregnant women may take advantage of GH
      substitution during pregnancy, but this issue still remains unresolved. Also, in
      pregnancy diabetes may cause macrosomia. The combination of GH deficiency, GH
      substitution therapy and type 1 diabetes mellitus may influence pregnancy in
      unforeseen ways. We present a case of pregnancy in a GH deficient woman with type
      1 diabetes who continued on GH replacement until week 21. In gestational week 37
      a thin and mildly small-for gestational-age (length 55 cm, +3 SD, 99th centile
      and weight 2445 g., -1.4 SD, 10th centile) but otherwise healthy boy was born.
      The patient had levels of serum hPGH at the lower end of the range of values
      found in a matching group of diabetic women. Serum IGF-I levels were at the upper
      end of the range of values in the control group. A positive correlation between
      serum hPGH and IGF-I values was seen in the control group when using the area
      under-the-curve (r=0.84; p<0.001). The patient's child had lower birth weight and
      ponderal index, but was otherwise healthy. Serum IGF-I, but not hPGH, correlated
      to the absolute birth weight (r=0.63; p=0.015) and the birth weight z-score
      (r=0.55; p=0.039) in the control group. Serum hPGH and IGF-I declined rapidly
      after delivery. In conclusion, hPGH correlated to IGF-I in type 1 diabetes
      mellitus (DM), and IGF-I values correlated to the birth weight. Both type 1
      diabetes mellitus and GH deficiency (with GH substitution therapy) may influence
      fetal growth, and in combination, the net influence may be difficult to predict.

PMID- 14700556
TI  - High levels of 150-kDa insulin-like growth factor binding protein three ternary
      complex in patients with acromegaly and the effect of pegvisomant-induced serum
      IGF-I normalization.
AB  - OBJECTIVE: To assess the effect of pegvisomant-induced serum insulin-like growth
      factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2
      and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated
      IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly.
      DESIGN: The above parameters were measured in 16 patients (median age 57 (range
      27-78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of
      an age-related reference range after washout) in a paired manner on samples
      obtained after washout and the first occurrence of serum IGF-I normalization
      during pegvisomant therapy (median dose 15 mg/day (10-40 mg)). RESULTS: Total
      IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly
      elevated in patients at baseline compared to controls ((mean+/-SEM) 4345+/-194
      vs. 3456+/-159 microg/L, P<0.01 and 3908+/-160 va. 3042+/-149 microg/L, P<0.01,
      respectively), but no significant difference in 45-kDa IGFBP-3 or in vivo IGFBP-3
      proteolysis was observed. Serum IGF-I normalization (699+/-76 to 242+/-28
      microg/L, P<0.0001) was associated with a fall in total IGFBP-3 (4345+/-194 to
      3283+/-160 microg/L, P<0.001) due to a reduction in 150-kDa ternary complex
      associated IGFBP-3 (3908+/-160 to 3008+/-140 microg/L, P<0.0001). 45 kDa IGFBP-3
      and in vivo IGFBP-3 proteolysis were unaffected by GH receptor blockade (326+/-13
      to 330+/-18 microg/L, P=0.86; 30+/-3.5 to 30+/-3.9%, P=0.75, respectively).
      CONCLUSIONS: GH receptor blockade in patients with acromegaly lowers IGF-I and
      150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not
      in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary
      complex-associated IGFBP-3 may provide useful information regarding treatment
      efficacy in patients with acromegaly.

PMID- 14700558
TI  - Binding affinity and biological activity of oxygen and sulfur isosteres at
      melatonin receptors as a function of their hydrogen bonding capability.
AB  - Analogues of melatonin (1) and of N-acetyl 5-ethoxytryptamine (3) in which the
      oxygen atoms are replaced by sulfur have been prepared and tested against human
      and amphibian melatonin receptors. All sulfur analogues show a decreased binding
      affinity at human MT1 and MT2 receptors and a reduced potency as melatonin
      agonists on the Xenopus melanophore assay. The 5-methoxy oxygen of melatonin is
      significantly more important for receptor binding than the amide oxygen. N-Acetyl
      5-ethoxytryptamine shows a decrease in both binding affinity and potency in
      comparison with melatonin. In this series, replacing either the ethoxy or amide
      oxygen by sulfur has a similar but smaller effect on both binding affinity and
      potency. Using K(B)(H) values from Abraham's equations we have assessed the
      possibility of estimating EC50 values for sulfur isosteres from the EC50 values
      of their oxygen analogues.

PMID- 14700559
TI  - A second-generation copper(II)-mediated metallo-DNA-base pair.
AB  - Metal-dependent pairing of nucleobases represents an alternative DNA base pairing
      scheme. Our first-generation copper(II)-mediated pyridine-2,6-dicarboxylate
      (Dipic) and pyridine (Py) metallo-base pair has a stability comparable to the
      natural base pairs dA:dT and dC:dG but does not have the selectivity of the
      Watson Crick base pairs. In order to increase the selectivity of base pair
      formation, a second-generation metallo-base pair was generated consisting of a
      pyridine-2,6-dicarboxamide (Dipam) and a pyridine (Py) nucleobase. This new
      metallo-base pair is more stable than the natural base pairs dA:dT and dC:dG and
      highly selective against mispairing. In addition, incorporation of multiple
      metallo-base pairs into DNA results in the formation of stable duplexes
      demonstrating that hydrogen bonding base pairs can efficiently be replaced by
      metal-dependent base pairs at multiple sites in DNA.

PMID- 14700560
TI  - Predominant role of basicity of leaving group in alpha-effect for nucleophilic
      ester cleavage.
AB  - It has been found that alpha-effects in nucleophilic reactions, unexpectedly
      large nucleophilicity due to adjacent unpaired electrons, are strongly dependent
      on the structure of substrate. The nucleophilic cleavages of 4-nitrobenzoate
      esters and 4-methylbenzoate esters by HOO- have been systematically investigated
      in detail. When the leaving groups of substrates are sufficiently good (aryl,
      2,2,2-trifluoroethyl, and 2,2-dichloroethyl esters), alpha-effect is evident.
      However, this effect drastically decreases as the leaving group gets poorer, and
      is only marginal for the cleavages of 2-fluoroethyl and methyl esters. In the
      nucleophilic cleavages by salicylaldoxime and acetohydroxamic acid, alpha-effect
      is also notable only for the esters having good leaving groups. These enormous
      dependences of alpha-effects on the substrate-structure have been interpreted in
      terms of the difference in the position of transition-state in the reaction
      coordinate.

PMID- 14700561
TI  - 13-Demethyl-13-substituted-13,14-dihydroretinols as potential affinity labels of
      retinol-binding proteins: syntheses and stability studies.
AB  - 13-Demethyl-13-substituted-13,14-dihydroretinols were synthesized and their
      stability under various conditions was measured in order to evaluate whether they
      would be useful as affinity labels of retinol binding proteins and retinol
      metabolizing enzymes. The 13-chloro analog could not be isolated because it
      eliminated HCl under the Wittig reaction conditions of its preparation. The trans
      and cis-13,14-epoxy analogs are stable in non-protic organic solvents, but
      undergo an elimination reaction under various chromatographic conditions and in
      mixtures of organic solvents with water or alcohol. The 13-hydroxy and 13-methoxy
      analogs are stable in aqueous solutions and are therefore suitable for biological
      studies.

PMID- 14700562
TI  - Tartrate dehydrogenase reductive decarboxylation: stereochemical generation of
      diastereotopically deuterated hydroxymethylenes.
AB  - Tartrate dehydrogenase catalyzes the reductive decarboxylation of meso-tartrate
      to glycerate. Concomitant with the ketonization of the intermediate enolate the
      C3 hydroxymethylene of glycerate necessarily acquires a proton from solvent. In
      D2O, the proton is shown to be added stereospecifically to form (2R,3R)-[3
      2H]glycerate. The 1H-NMR assignments of the diastereotopic C3 protons of
      glycerate were confirmed by the enzymatic conversion of [1R-2H]fructose-6
      phosphate to (2R,3R)-[3-2H]glycerate. The decarboxylation-protonation occurs with
      retention of configuration, implying that the general acid is positioned on the
      same face of the intermediate as the departing carboxylate. The stereochemically
      pure (2R,3R)-[3-2H]glycerate is readily synthesized and serves as a chiral
      hydroxymethylene synthon as demonstrated by the synthesis of (2S,3R)-[3
      2H]serine.

PMID- 14700563
TI  - Responding to emotional trauma.

PMID- 14700564
TI  - Improving Door-to-Drug time and ST segment resolution in AMI by moving
      thrombolysis administration to the Emergency Department.
AB  - BACKGROUND: We describe a combination of measures to reduce Door-to-Drug (DTD)
      time and improve the Emergency Department (ED) management of ST elevation MI
      (STEMI): appointment of a Cardiology Nurse Specialist, application of the
      American College of Cardiology and the American Heart Association (ACC/AHA)
      guidelines, changing the site of thrombolysis from the CCU to the ED, the
      introduction of a single bolus thrombolytic agent. METHODS: The 12-month period
      before and after the introduction of the measures were retrospectively reviewed.
      One hundred and sixty patients were discharged from the CCU with the diagnosis of
      myocardial infarction confirmed by ECG and enzyme criteria. Eighty patients had
      STEMI and fulfilled criteria for thrombolytic therapy at the time of presentation
      to hospital. A full data set was available on 35/38 of patients in the 12 months
      prior to the measures (Year 1), and 39/42 in the 12 months subsequent (Year 2).
      RESULTS: Median DTD time fell from 80 to 22 min after institution of the
      measures. Median Pain-to-Drug time also fell from 270 to 140 min. Thrombolytic
      agent given in the ED rose from 3% in Year 1, to 72% in Year 2. IV beta-blocker
      administered in the ED rose from 12% to 79%, resulting in median time to
      receiving IV beta-blocker falling from 63 to 19 min. Elevated ST segments
      resolved by >/=70% in <2 h in 53% of Year 2 patients, compared with 23% of Year 1
      patients. Combined major in-hospital adverse clinical events were reduced from
      49% to 15%. CONCLUSION: This combination of measures reduces DTD time, improves
      speed to delivery of important concomitant medications, and significantly
      improves the time to ST segment resolution and outcome in STEMI.

PMID- 14700565
TI  - Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case
      controlled study.
AB  - INTRODUCTION: Since its introduction in 1977, intravenous N-acetylcysteine has
      become the treatment of choice for paracetamol overdose. The aim of our study was
      to investigate the existence of predictive factors in the likelihood of
      developing anaphylactoid reactions to N-acetylcysteine. METHODS: Prospective case
      controlled study of all patients who presented to our emergency department (ED)
      between January 1997 and June 1999, and who were treated with intravenous N
      acetylcysteine on the short stay observation ward. RESULTS: Sixty-four patients
      received N-acetylcysteine infusions; thirty-one (48.4%) developed an
      anaphylactoid reaction. Nineteen patients who reacted were commenced on N
      acetylcysteine prior to receipt of paracetamol concentrations and fifteen (48.4%)
      were categorised as high-risk. Seventy-one percent of reactions occurred within
      the first 15 min. Thirteen patients who developed a reaction, had levels which
      fell below the treatment lines. The levels of a further nine reactors lay above
      the high-risk but below the normal-risk lines. Only five patients who reacted had
      levels above the normal-risk line. Two of the patients who reacted to intravenous
      N-acetylcysteine presented at a later date with a further paracetamol overdose.
      Both required treatment with intravenous N-acetylcysteine, the first bag being
      infused over one hour. Neither developed a reaction. CONCLUSION: We report a
      substantially higher incidence of anaphylactoid reactions to intravenous N
      acetylcysteine than has previously been documented. It appears that these
      reactions are more likely to occur in high-risk patients, when plasma paracetamol
      concentrations were found to be below the treatment lines and in late presenters.
      Perhaps, giving the loading dose of N-acetylcysteine over 60 min could reduce the
      incidence of adverse reactions.

PMID- 14700566
TI  - The Anaphylaxis Campaign.

PMID- 14700567
TI  - Can nurses, working in the emergency department, independently clear cervical
      spines?: a review of the literature.
AB  - The prompt clearance of a patient's cervical spine is extremely beneficial both
      to the patients and the department however correct guidelines and education must
      be established before this can be undertaken safely. This paper examines whether
      nurses given the appropriate training and education using appropriate diagnostic
      and clinical criteria can safely, effectively clear cervical spines without
      consulting a medical practitioner. The paper explores the use of the Nexus
      Guidelines [J.R. Hoffman, W.R. Mower, A.B. Wolfson, New England Journal of
      Medicine 343 (2) (2000) 94-99] as a clinical prediction tool and presents
      evidence for its use.

PMID- 14700568
TI  - Evaluation of a 'See and Treat' pilot study introduced to an emergency
      department.
AB  - OBJECTIVE: To assess the effectiveness of a 'See and Treat' system on waiting
      times for patients attending an Emergency Department with minor injuries and
      illnesses. METHODS: Retrospective analysis of statistics collected during two
      study periods and compared for evaluation. RESULTS: The percentage of patients
      assessed within 15 min increased from 82% to 98%. The percentage of patients seen
      within 1 h of arrival rose from 63% to 90% using 'See and Treat'. The percentage
      of patients discharged within 1 h rose from 16% to 41%. The average wait to see a
      doctor or emergency nurse practitioner dropped from 56 to 30 min. The total
      average time in the department dropped from 1 h 39 min to 1 h 17 min. During 'See
      and Treat' the waiting times for all patients within the department were also
      reduced. CONCLUSION: 'See and Treat' reduces waiting times for patients with
      minor injuries and illnesses and has a positive effect on waiting times for
      patients elsewhere in the department.

PMID- 14700569
TI  - Adult epiglottitis.
AB  - Epiglottitis is supraglottic inflammation of the oropharynx caused by infective,
      thermal, or caustic insult. Rapid swelling of the epiglottis results in airway
      obstruction and asphyxia. Widespread use of HiB vaccination in children has
      resulted in a reduction in childhood cases of epiglottitis. The majority of
      adults have not received vaccination, and remain susceptible. Peak incidence is
      in the 35- to 39-year-old age group with an annual incidence of 0.97-1.8/100,000,
      approximately 2.5 times the incidence in children (Sack and Brock, 2002; Carey,
      1996; Fontanarosa et al., 1989). We present three cases of adult epiglottitis
      presenting to a District Hospital Accident and Emergency (A&E) department in
      Yorkshire over a six-month period.

PMID- 14700570
TI  - Emergency department mental health triage consultancy service: an evaluation of
      the first year of the service.
AB  - This article presents the findings of a review of the first year of a night
      emergency department (ED) mental health triage and consultancy service. During
      the first 12 months of operation of the service, data on key performance
      indicators were entered into an emergency mental health triage and consultancy
      database. Data were also obtained from pre- and post-satisfaction surveys
      completed by ED staff and from self-appraisal statements generated by the five
      mental health nurses who undertook the position during the review period. The
      findings show the ED mental health triage and consultancy service positively
      impacted on the functioning of the emergency department. This was evidenced by
      staff' perceptions regarding the value of the service and through shorter "seen
      by times", a reduction in the number of patients with psychiatric/psychosocial
      problems who left the department without being seen, and the effective management
      of patients presenting with psychiatric/psychosocial problems, particularly those
      presenting with deliberate self-harm. The review provided evidence regarding the
      value of the emergency mental health triage and consultancy service and
      highlighted the advanced practice role undertaken by mental health nurses in this
      position.

PMID- 14700571
TI  - Nurses' acquisition and retention of knowledge after trauma training.
AB  - The Advanced Trauma Nursing Course (ATNC) aims to equip nurses with the
      appropriate knowledge in order to skilfully care for the trauma patient. In this
      study, knowledge gained from the course, and its subsequent retention, was used
      as a measure of the course's effectiveness. Fourteen nurses participated in the
      study. The ATNC short answer papers were used to assess knowledge levels of the
      participants at four separate stages. Statistical analysis demonstrated a highly
      significant change (p<0.001) in the knowledge levels of ATNC participants
      following attendance on the course. However, three months after the ATNC
      knowledge levels appeared not to be statistically significantly different from
      pre-course levels, which suggested that retention of knowledge was poor. The
      findings of this study highlight the importance of continuous professional
      development and, in particular, the need to implement local initiatives aimed at
      improving the retention of knowledge gained by ATNC participants.

PMID- 14700572
TI  - Consensus statement on crush injury and crush syndrome.
AB  - Crush syndrome remains rare in European practice. It is, however, common in areas
      of civil disorder and where the normal structures of society have given way to
      civil war or natural disaster. Western doctors are becoming increasingly involved
      in such situations and there is no reason to believe that instances due to more
      conventional causes, such as collapse in the elderly or road traffic accidents
      will cease. For all these reasons it is important that clinicians who deal
      infrequently with crush syndrome have access to appropriate guidelines. This
      consensus report seeks to provide such advice.

PMID- 14700573
TI  - Consensus on the pre-hospital approach to burns patient management.
AB  - Burns patients form a large group of trauma patients cared for by first aiders,
      ambulance staff, nurses and doctors before reaching specialist care in hospital.
      Guidance for these important carers is often poor or confused and this engenders
      anxiety and detracts from optimal patient care. This paper outlines nine key
      steps in the initial management of burn patients in the pre-hospital environment
      based on current available evidence and a consensus of specialists from all
      disciplines caring for burns patients. The basis of care should be that simple
      things should always be performed well.

PMID- 14700574
TI  - Traumatic pseudorupture of the diaphragm.

PMID- 14700579
TI  - Population genetics of Cryptosporidium parvum.

PMID- 14700578
TI  - Sulfa drugs strike more than once.

PMID- 14700581
TI  - Cell volume control in the Plasmodium-infected erythrocyte.

PMID- 14700583
TI  - A role for the peripheral blood fibrocyte in leishmaniasis?

PMID- 14700584
TI  - Apicomplexan gliding motility and host cell invasion: overhauling the motor
      model.

PMID- 14700585
TI  - Vaccination: a way to address questions in behavioral and population ecology?

PMID- 14700586
TI  - Parasite and host contributions to the pathogenesis of amebic colitis.

PMID- 14700587
TI  - Arthropod-transmitted diseases of companion animals in Southeast Asia.

PMID- 14700588
TI  - Specific and sensitive diagnosis of schistosome infection: can it be done with
      antibodies?

PMID- 14700589
TI  - Molecular regulation of the life cycle of African trypanosomes.

PMID- 14700590
TI  - Pathogenesis of diseases associated with antineutrophil cytoplasm autoantibodies.
AB  - Little is known about the etiologies of diseases associated with circulating
      antineutrophil cytoplasm autoantibodies (ANCA), such as primary vasculitides and
      inflammatory bowel diseases. However, the understanding of immune mechanisms
      supposedly involved in the pathogenesis of these diseases is still growing. In
      the present review, we first focus on the mechanisms triggering the development
      of ANCA, including the potential role of microbial superantigens and the possible
      defect(s) in the progression of apoptosis or in the removal of apoptotic cells.
      We next concentrate on the contribution of ANCA to the clinical symptoms and on
      the pathogenic role of ANCA, including the accessibility of ANCA antigens as
      targets for circulating antibodies and the mode of action of ANCA. Mechanisms of
      neutrophil activation by ANCA include the engagement of Fcgamma receptors, the
      possible mechanisms of neutrophil-mediated tissue damage, and the neutrophil
      endothelial interaction.

PMID- 14700591
TI  - The HLA-DR phenotype of the responder is predictive of humoral response against
      HLA class I antigens.
AB  - Recent studies suggest that the immunogenicity of an human leukocyte antigen
      (HLA) incompatibility should be considered in the context of the HLA phenotype of
      the recipient. The HLA-DR phenotype of the responder is thought to be predictive
      for the strength of the alloimmune response. In order to analyze the humoral
      response against HLA class I antigens in the context of the HLA-DR phenotype of
      the responder, we selected all HLA-DR homozygous Dutch patients that were present
      on the Eurotransplant waiting list between 1967 and 2000 (n=1,317 patients). By
      logistic regression it was determined whether antibody production against a
      specific HLA class I antigen is associated with a particular HLA-DR antigen in
      the patient. Furthermore, it was analyzed whether a patient, expressing a
      particular HLA-DR antigen, preferentially produces antibodies against particular
      HLA class I antigens. The results demonstrate that patients, homozygous for a
      certain HLA-DR antigen, cannot be considered high or low responders when
      analyzing the antibody response in terms of panel reactive antibody (PRA) value.
      However, a correlation can be found between the HLA-DR phenotype of the patient
      and the specific antibody response against HLA class I antigens. For example,
      antibodies against HLA-A10, -A11, -A19, and -B35 are produced more frequently by
      HLA-DR6 positive individuals, whereas antibodies against HLA-A3, -B5, -B7, -B8,
      and -B12 are produced more frequently by HLA-DR4 positive individuals. These data
      confirm that the HLA-DR phenotype of the responder plays a determinative role in
      the immunogenicity of mismatched HLA antigens. The results indicate that
      selection of HLA class I mismatches of the donor in the context of the HLA-DR
      phenotype of the responder might reduce the incidence of humoral graft rejection
      and minimize the sensitization grade of retransplant candidates.

PMID- 14700592
TI  - Evidence for two independent distributions of serum immunoglobulin E in atopic
      families: cognate and non-cognate IgE.
AB  - Genetic studies of IgE-mediated atopic disease have produced conflicting results,
      due largely to variable phenotype definitions. Total IgE concentrations and 14
      allergen skin prick tests (SPT) were determined in 1099 members of families with
      history of atopy. Log10 [Total IgE] values were normally distributed in both
      atopic (SPT [+]) and non-atopic (SPT [-]) groups. The mean Log10 [Total IgE]
      value was higher in the atopic group, although the standard deviations of the
      distributions were the same. The mean Log10 [Total IgE] value of the non-atopic
      distribution was subtracted from the individual Log10 [Total IgE] values of the
      atopic group giving an allergen-specific fraction. There was a strong positive
      correlation between the specific IgE fraction and the number (#) SPT [+] results,
      defined as Cognate IgE. Among the atopics, subtracting the Cognate IgE value from
      total IgE yielded Non-Cognate IgE. The Cognate and Non-Cognate IgE distributions
      were statistically uncorrelated. Evidence is presented for two serum IgE
      fractions that are statistically and physiologically independent of one another
      in atopic families; a Cognate IgE fraction associated with atopic sensitization
      and a Non-Cognate IgE fraction unrelated to atopic disease. Elevated serum IgE is
      a consequence, not a predisposing cause, of allergen sensitization.

PMID- 14700593
TI  - Investigation of killer cell immunoglobulinlike receptor gene diversity: I.
      KIR2DL4.
AB  - Polymerase chain reaction-sequence-specific oligonucleotide probes typing
      procedures identifying alleles of the killer immunoglobulin-like gene (KIR2DL4)
      have been established. The methods, designed around the specific amplification of
      the D0 and D2 domains of this gene, produce discrimination of KIR2DL4 alleles.
      The methods have been applied to a healthy Northern Irish control group,
      establishing frequencies for this Caucasian population. Additionally, the KIR2DL4
      allele status of cell line DNA and CEPH families, from the 13th International
      Histocompatibility Workshop and local families, have also been investigated.

PMID- 14700594
TI  - HLA-G is associated with pemphigus vulgaris in Jewish patients.
AB  - Pemphigus is a group of life-threatening autoimmune blistering diseases of the
      skin and mucous membranes. The etiology and pathogenesis of this destructive
      autoimmune process remains unknown, but significant association with human
      leukocyte antigen (HLA) factors have been described in pemphigus vulgaris (PV)
      patient cohorts worldwide. We have recently analyzed DNA samples obtained from
      pemphigus patients and matched controls with a set of microsatellite markers, and
      found that markers mapped to HLA class I region are significantly associated with
      the disease. In order to narrow the region that is associated with the disease
      single nucleotide polymorphism (SNP) technology was used. In this study, a set of
      26 SNP markers, which span a chromosomal region of about 600,000 bp, were used to
      screen DNA samples of the patients and their matched controls. Of the 26 SNPs,
      four markers were found informative, all mapped to HLA-G. Typing patients and
      controls for HLA-G polymorphism revealed significant differences in the exon 8
      deletion/insertion variant. The latter is probably associated with the efficiency
      of transcription of this gene. Taken together, the results suggest that HLA-G is
      associated with PV in Jewish patients.

PMID- 14700596
TI  - HLA class II and class I polymorphism in Venezuelan patients with myasthenia
      gravis.
AB  - Oligotyping performed among ethnically mixed Venezuelan patients with myasthenia
      gravis (MG) and controls has revealed positive associations of HLA class I A*31,
      B*08, B*39, B*40, C*15, C*17, and class II DRB1*09 and negative associations of
      DQB1*06 and DQA1*02 with the disease. Sequential removal of human leukocyte
      antigen B (HLA-B) alleles when relative predispositional effects (RPEs) were
      looked for demonstrated that B*08 is the allele group with the largest
      contribution in the overall MG patients followed by B*39 and B*40. Several
      specificities (A*31, B*08, C*17, DRB1*03, DQA1*05, and DQB1*02) indicated
      increased frequencies among patients with thymic hyperplasia versus patients
      without hyperplasia or controls. Tests to identify alleles with the strongest
      association to MG in our patients detected DRB1*13 and B*38 as possible
      predisposing secondarily associated alleles in patients with hyperplasia. The
      associations observed disappear after Bonferoni correction of probability values
      and have been described in patients of Caucasian and/or Oriental ethnic
      background. Thus, our results reflect the heterogeneity of our population and of
      the patients tested and suggest a limited influence of several HLA genes in this
      heterogeneous disease or that these might be only markers of nearby non-HLA genes
      responsible for the susceptibility or resistance effect.

PMID- 14700595
TI  - HLA haplotypes associated with type 1 diabetes mellitus in North Indian children.
AB  - Human leukocyte antigen (HLA) encoded susceptibility to develop type 1 diabetes
      mellitus (T1DM) has been investigated in children from North India. The results
      revealed significantly increased prevalence of HLA-A26, -B8, and -B50 among
      patients and strong positive association of the disease with DRB1*0301 (82.1% vs
      13.9%, chi2=71.3, odds ratio [OR]=28.3) and a negative association with DRB1*02
      (chi2=12.2, PF=38.5). HLA-DQB1*0201 occurred in 96.4% of the patients, whereas
      the heterodimer DQA1*0501-DQB1*0201 was present in 82.1% of patients (60.7% in
      single dose and 21.4% in double dose) and revealed significant deviation from the
      healthy controls (chi2=74.1, pc=6.0E-10). In addition to DRB1*03, positive
      association was also observed with DRB1*09 (14.3% vs 1.3%, chi2=13.4) and DRB1*04
      (39.3% vs 15.6%, chi2=8.39). No HLA association was observed in relation to
      residual pancreatic beta-cell function or associated thyroid autoimmunity. Family
      analysis revealed involvement of multiple DR3+ve haplotypes with T1DM in North
      Indian children with A26-B8-DRB1*03 (25% vs 3.5%, chi2=16.9, p=3.96E-05) and Ax
      B50-DRB1*03 (25% vs 0.7%, chi2=44.7, p=9.88E-11) being the most frequent
      haplotypes encountered among patients. The classical Caucasian haplotype A1-B8
      DRB1*03 was infrequent (7.2%) among the diabetic children. The study highlights
      the race specificity of HLA association and disease associated HLA haplotypes in
      T1DM among North Indian children.

PMID- 14700597
TI  - MHC class I and class II genes in Mexican patients with Chagas disease.
AB  - Chagas' disease contributes significantly to cardiovascular morbidity and
      mortality in several Latin-American countries. Previous studies have reported the
      effect of the human leukocyte antigen (HLA) molecules in the immune response
      regulation of Trypanosoma cruzi infection, and the association of HLA antigens
      with heart damage. We studied the major histocompatibility complex (MHC) class I
      (HLA-A and HLA-B), and class II (HLA-DR) genes in a sample of 66 serologically
      positive individuals with and without cardiomyopathy, and in 127 healthy
      controls. The total group of seropositive individuals revealed increased
      frequencies of HLA-B39 (pc=4.3x10(-5), odds ratio [OR]=3.35) and DR4 (pc=1.8x10(
      5), OR=2.91) when compared to healthy controls. Increased frequencies of HLA-A68
      and HLA-B39 were found in asymptomatic individuals when compared to patients with
      cardiomyopathy (pc=0.014, OR=4.99 and pc=0.001, OR=4.46, respectively). Also,
      patients with cardiomyopathy exhibited increased frequency of HLA-B35 when
      compared to healthy controls (pc=0.048, OR=2.56). The HLA-DR16 frequency was
      increased in patients with cardiomyopathy compared with asymptomatic individuals
      (pc=0.05, OR=No determined) and healthy controls (pc=0.02, OR=5.0). The results
      suggest that MHC alleles might be associated with the development of chronic
      infection and with heart damage in Chagas' disease. HLA-DR4 and HLA-B39 could be
      associated directly with the infection by T. cruzi, whereas, HLA-DR16 could be
      marker of susceptibility to heart damage and HLA-A68 might confer protection to
      develop cardiomyopathy.

PMID- 14700598
TI  - High resolution HLA-DRB1 identification of a Caucasian population.
AB  - Polymerase chain reaction-sequence-specific oligonucleotide probes typing methods
      have been applied to 1000 individuals from the Northern Ireland population to
      give human leukocyte antigen DRB1 (HLA-DRB1) allele assignment. HLA-DRB1 allele
      frequencies and four-locus haplotypes (A/B/C/DR) for this Caucasian population,
      based on HLA class I and class II allele assignment, are now presented. No
      significant deviations from Hardy-Weinberg proportions were observed. The HLA-C
      locus exhibited marginal evidence of selection (p<0.03, uncorrected one-sided
      test) in the direction of balancing selection; the HLA-A, -B, and -DRB1 allele
      frequency distributions were compatible with expectations under a neutral model
      (which does not mean that selection is not operating). Evidence for selection was
      seen on haplotypes HLA-A*010101-B*0801-DRB1*030101 and HLA-A*290201-B*440301
      DRB1*070101 based on their patterns of linkage disequilibrium.

PMID- 14700599
TI  - HLA alleles and haplotypes among the Lakota Sioux: report of the ASHI minority
      workshops, part III.
AB  - Human leukocyte antigen (HLA) class I and II alleles were defined for 302 Lakota
      Sioux American Indians as part of the American Society for Histocompatibility and
      Immunogenetics coordinated studies on minority populations. The study group was
      comprised of adult volunteers from the Cheyenne River and Ogala Sioux tribes
      residing, respectively, on the Cheyenne River and Pine Ridge Reservations in
      South Dakota. Of the participants, 263 (87%) claimed full American Indian
      ancestry through both maternal and paternal grandparents. The study group
      included 25 nuclear families that were informative for genotyping. HLA phenotypes
      from 202 adults with no other known first-degree relative included in the study
      were used for calculation of allele and haplotype frequencies by maximum
      likelihood estimation. HLA-A, -B, and -Cw alleles were found to be in Hardy
      Weinberg equilibrium. Deviation from equilibrium was observed for DRB1 alleles
      (p=0.01), but could be attributed to the sample size and the occurrence of some
      genotypes with low expected frequencies. Polymorphism among the Sioux was limited
      with four to seven alleles comprising >80% of those observed at each locus.
      Several alleles were found at high frequency (0.05-0.30) among the Sioux that are
      also prevalent in other Native Americans and Alaska Natives, including: A*2402,
      *3101, and *0206; B*3501,*3901, *5101, and *2705; Cw*0702, *0404, and *03041;
      DRB1*0407, *0404, *1402, and *16021; and DQB1*0301, *0302, and *0402. DRB1*0811,
      which has been only previously described in Navajo and Tlingit Indians, was found
      to occur at a frequency of 0.119 among the Sioux. Two new alleles were defined
      among the Sioux: Cw*0204 and DRB1*040703, which were found in two and four
      individuals, respectively. In the haplotype analyses, significant linkage
      disequilibrium (p<0.00001) was seen in all pairwise comparisons of loci and
      numerous two and three locus haplotypes were found to have strong, positive
      linkage disequilibrium values. The two most common extended haplotypes among the
      Sioux, determined by maximum likelihood estimation and genotyping were: A*31012,
      B*3501, Cw*0404, DRB1*0407; and A*24021, B*3501, Cw*0404, DRB1*0404.

PMID- 14700600
TI  - Nomenclature for factors of the HLA system, update September 2003.

PMID- 14700601
TI  - Epoetin: for better or for worse?

PMID- 14700602
TI  - Endothelial-cell apoptosis and tumour response to radiotherapy.

PMID- 14700603
TI  - New frontiers or red herrings in radiation oncology?

PMID- 14700604
TI  - Part I: Hodgkin's lymphoma--molecular biology of Hodgkin and Reed-Sternberg
      cells.
AB  - Classic Hodgkin's lymphoma is characterised by Hodgkin and Reed-Sternberg cells
      and in most cases are derived from germinal-centre B cells. Despite progress in
      basic research showing the natural precursor cells of Hodgkin's lymphoma, most
      key questions still remain unanswered. Among these are the basic transforming
      events, the involvement of oncogenic viruses, the mechanisms enabling Hodgkin and
      Reed Sternberg cells to resist apoptosis in the germinal centre, and the
      molecular causes of their characteristic phenotype. Beyond the disclosure of
      these issues, the detection of changes in gene expression, gene mutations, and
      chromosomal imbalances specific of Hodgkin's lymphoma are central to recent
      research that may allow one a better understanding of the natural history of this
      type of lymphoma.

PMID- 14700605
TI  - Part II: Hodgkin's lymphoma--diagnosis and treatment.
AB  - The outcome of patients with all stages of Hodgkin's lymphoma has improved
      dramatically over the past few decades. This is mainly due to the use of risk
      adapted therapies using intensive polychemotherapeutic regimens in combination
      with other modalities. Patients with early favourable or unfavourable
      (intermediate) stage disease receive two or four cycles of chemotherapy,
      respectively, followed by involved-field radiotherapy (20-30Gy). Advanced stage
      Hodgkin's lymphoma is treated more aggressively using six to eight cycles of
      chemotherapy but the effectiveness of consolidative radiotherapy for patients who
      show a complete response after chemotherapy alone is still unknown. The main
      challenge in the near future will be the development of strategies that decrease
      late morbidity and mortality but retain the same efficacy of current regimens. In
      this paper we review current diagnostic techniques and management strategies used
      to treat Hodgkin's lymphoma, and the range of new modalities being used to
      improve long-term outcome and patient quality of life.

PMID- 14700606
TI  - Cell-cycle targeted therapies.
AB  - Eukaryotic organisms depend on an intricate and evolutionary conserved cell cycle
      to control cell division. The cell cycle is regulated by a number of important
      protein families which are common targets for mutational inactivation or
      overexpression in human tumours. The cyclin D and E families and their cyclin
      dependent kinase partners initiate the phosphorylation of the retinoblastoma
      tumour suppressor protein and subsequent transition through the cell cycle.
      Cyclin/cdk activity and therefore control of cell division is restrained by two
      families of cyclin dependent kinase inhibitors. A greater understanding of the
      cell cycle has led to the development of a number of compounds with the potential
      to restore control of cell division in human cancers. This review will introduce
      the protein families that regulate the cell cycle, their aberrations in malignant
      progression and pharmacological strategies targeting this important process.

PMID- 14700607
TI  - Management of Wilms' tumour: current practice and future goals.
AB  - Most patients with Wilms' tumour in Europe and North America can be cured with
      treatment and subsequently lead a normal adulthood. However, for some, therapy as
      applied today results in long-term side-effects and creates a substantial burden
      on quality of life. Therefore, investigators involved in the management of
      patients with Wilms' tumour are increasingly focusing their efforts on curtailing
      the long-term sequelae of therapy. This aim has been achieved by lowering the
      total amount of chemotherapy, radiotherapy, or both administered to patients who
      have characteristics associated with favourable outcome. Although excellent
      survival has been maintained, many patients receive less therapy today than
      patients with similar characteristics did a decade or two ago. Better
      understanding of the biological processes that lead to this childhood cancer will
      allow further improvements in its management.

PMID- 14700608
TI  - Immunobiology of haematological malignant disorders: the basis for novel
      immunotherapy protocols.
AB  - The immune system is a complex arrangement of cellular interactions that preserve
      the integrity of a organism by elimination of all elements judged dangerous.
      However, the development of tumours in immunocompetent patients suggests the
      existence of an imbalance that favours tumour cells against the immune response.
      What are the different possibilities for reversing this process to drive an
      efficient antitumour response? We discuss, focusing on the haematological
      features, classic immunity (ie, antigen-specific and HLA-restricted immunity). We
      address the central issues of tumour antigen presentation and recognition and
      their possible clinical use. Last, we discuss non-HLA-restricted immunity, which
      does not require the recognition of specific antigens and relies on particular
      cell populations such as natural killer cells.

PMID- 14700609
TI  - Sublaryngeal cancer of the trachea.

PMID- 14700610
TI  - Testicular cancer: the challenge for cancer control.
AB  - The effect of the discovery of a curative treatment regimen for testicular cancer
      is apparent in countries with declining national mortality rates. The
      introduction of centralised treatment in Slovakia has been maintained, and the
      decline seen in the former country referred to as East Germany after rapid
      economic change is also clear and continuing. However, mortality remains higher
      in all countries of central and eastern Europe, compared with western European
      countries. Testicular cancer could almost be eliminated as a cause of death
      worldwide if the political will, adequate finance, and the necessary training and
      logistics to deliver appropriate treatment were implemented. The resources
      required to eliminate death from testicular cancer are resource-based, rather
      than dependent on the outcome of further research. The aim of all cancer research
      is to benefit the patient with cancer or those who are at risk of developing the
      disease. Testicular cancer control would be the finest illustration of this
      process and, simultaneously, would be a model for implementation as new,
      successful therapeutic modalities for other cancers are developed.

PMID- 14700611
TI  - Myeloid sarcoma of the prostate as first clinical manifestation of acute myeloid
      leukaemia.

PMID- 14700612
TI  - Treating two concurrent B-cell and T-cell lymphoid neoplasms with alemtuzumab
      monotherapy.

PMID- 14700616
TI  - Uncomfortable statistics.

PMID- 14700617
TI  - Metaphore Pharmaceuticals: mimicking nature's enzyme.

PMID- 14700618
TI  - How to find "missing" genes.
AB  - Assigning function to "new" proteins is frequently the rate-determining step for
      deciphering metabolic pathways and regulatory networks. Osterman and Begley break
      down this barrier by demonstrating that comparative analyses of microbial genomes
      is a powerful strategy for identifying pathway components.

PMID- 14700619
TI  - Summing up ligand binding interactions.
AB  - Artificial molecular recognition systems show negligible positive binding
      cooperativity compared to biological systems, possibly because rigid ligands
      cannot accommodate numerous partly bound states that comprise overall ligand
      binding affinity. This directly correlates with the phenomenon of enthalpy
      entropy compensation.

PMID- 14700620
TI  - CDK versus GSK-3 inhibition: a purple haze no longer?
AB  - The ubiquitous ATP binding site offers a global target for protein kinase
      inhibitors. The corollary is that molecular selectivity with such agents may be
      difficult to achieve and ascertain. A relevant example is discussed in terms of
      design and biomedical rationale.

PMID- 14700621
TI  - RNA as multitude/RNA as one.
AB  - In the configurations formed by RNA and its ions there are structural
      possibilities not yet realized; some are hinted at in new work on the binding of
      an amino acid analog.

PMID- 14700622
TI  - RNA sex.
AB  - Recombination of genetic information is a major driving force in evolution, today
      catalyzed by protein enzymes. In this issue of Chemistry & Biology, a paper by
      Riley and Lehman demonstrates that RNA can perform general recombination of RNA
      strands, thus supporting the scenario of a prebiotic RNA world.

PMID- 14700623
TI  - At the crossroads of chemistry, biology, and materials: structural DNA
      nanotechnology.
AB  - Structural DNA nanotechnology consists of combining unusual DNA motifs by
      specific structurally well-defined cohesive interactions (primarily sticky ends)
      to produce target materials with predictable 3D structures. This effort has
      generated DNA polyhedral catenanes, robust nanomechanical devices, and a variety
      of periodic arrays in two dimensions. The system has been used to produce
      specific patterns on the mesoscale through designing and combining specific DNA
      strands, which are then examined by atomic force microscopy. The combination of
      these constructions with other chemical components is expected to contribute to
      the development of nanoelectronics, nanorobotics, and smart materials. The
      organizational capabilities of structural DNA nanotechnology are just beginning
      to be explored, and the field is expected ultimately to be able to organize a
      variety of species that will lead to exciting and possibly revolutionary
      materials.

PMID- 14700624
TI  - Smart polymeric materials: emerging biochemical applications.
AB  - Smart polymeric materials respond with a considerable change in their properties
      to small changes in their environment. Environmental stimuli include temperature,
      pH, chemicals, and light. "Smart" stimuli-sensitive materials can be either
      synthetic or natural. This review discusses the application of smart materials as
      tools to solve biological problems such as bioseparation, drug delivery,
      biosensor design, tissue engineering, protein folding, and microfluidics. The
      goal for these endeavors is to mimic the "smartness" of biological systems and
      ultimately moderate complex systems such as immune responses at desired levels.
      The versatility and untapped potential of smart polymeric materials makes them
      one of the most exciting interfaces of chemistry and biology.

PMID- 14700625
TI  - Designer gene therapy using an Escherichia coli purine nucleoside
      phosphorylase/prodrug system.
AB  - Activation of prodrugs by Escherichia coli purine nucleoside phosphorylase (PNP)
      provides a method for selectively killing tumor cells expressing a transfected
      PNP gene. This gene therapy approach requires matching a prodrug and a known
      enzymatic activity present only in tumor cells. The specificity of the method
      relies on avoiding prodrug cleavage by enzymes already present in the host cells
      or the intestinal flora. Using crystallographic and computer modeling methods as
      guides, we have redesigned E. coli PNP to cleave new prodrug substrates more
      efficiently than does the wild-type enzyme. In particular, the M64V PNP mutant
      cleaves 9-(6-deoxy-alpha-L-talofuranosyl)-6-methylpurine with a kcat/Km over 100
      times greater than for native E. coli PNP. In a xenograft tumor experiment, this
      compound caused regression of tumors expressing the M64V PNP gene.

PMID- 14700626
TI  - Inhibitor specificity via protein dynamics: insights from the design of
      antibacterial agents targeted against thymidylate synthase.
AB  - Structure-based drug design of species-specific inhibitors generally exploits
      structural differences in proteins from different organisms. Here, we demonstrate
      how achieving specificity can be aided by targeting differences in the dynamics
      of proteins. Thymidylate synthase (TS) is a good target for anticancer agents and
      a potential target for antibacterial agents. Most inhibitors are folate-analogs
      that bind at the folate binding site and are not species specific. In contrast,
      alpha156 is not a folate-analog and is specific for bacterial TS; it has been
      shown crystallographically to bind in a nonconserved binding site. Docking
      calculations and crystal structure-based estimation of the essential dynamics of
      TSs from five different species show that differences in the dynamics of TSs make
      the active site more accessible to alpha156 in the prokaryotic than in the
      eukaryotic TSs and thereby enhance the specificity of alpha156.

PMID- 14700627
TI  - NAD biosynthesis: identification of the tryptophan to quinolinate pathway in
      bacteria.
AB  - Previous studies have demonstrated two different biosynthetic pathways to
      quinolinate, the universal de novo precursor to the pyridine ring of NAD. In
      prokaryotes, quinolinate is formed from aspartate and dihydroxyacetone phosphate;
      in eukaryotes, it is formed from tryptophan. It has been generally believed that
      the tryptophan to quinolinic acid biosynthetic pathway is unique to eukaryotes;
      however, this paper describes the use of comparative genome analysis to identify
      likely candidates for all five genes involved in the tryptophan to quinolinic
      acid pathway in several bacteria. Representative examples of each of these genes
      were overexpressed, and the predicted functions are confirmed in each case using
      unambiguous biochemical assays.

PMID- 14700628
TI  - A new H/D exchange- and mass spectrometry-based method for thermodynamic analysis
      of protein-DNA interactions.
AB  - The application of SUPREX (stability of unpurified proteins from rates of H/D
      exchange) to the thermodynamic analysis of protein-DNA complexes is described. A
      series of five model protein-DNA complexes involving two known DNA binding
      proteins, Arc repressor and CopG, were analyzed in order to determine the
      accuracy, precision, and generality of the SUPREX technique for quantifying the
      strength of protein-DNA interactions. For protein-DNA complexes that reversibly
      unfold in a two-state manner, we demonstrate that reasonably precise Kd values in
      agreement with those determined by conventional techniques can be determined by
      SUPREX. In the case of protein-DNA complexes that are not well modeled by a two
      state unfolding mechanism, we find that relative binding affinities can be
      determined in the SUPREX experiment.

PMID- 14700629
TI  - Biosynthesis of deoxyamphotericins and deoxyamphoteronolides by engineered
      strains of Streptomyces nodosus.
AB  - Amphotericin B is an antifungal antibiotic produced by Streptomyces nodosus.
      During biosynthesis of amphotericin, the macrolactone core undergoes three
      modifications: oxidation of a methyl branch to a carboxyl group,
      mycosaminylation, and hydroxylation. Gene disruption was undertaken to block two
      of these modifications. Initial experiments targeted the amphDIII gene, which
      encodes a GDP-D-mannose 4,6-dehydratase involved in biosynthesis of mycosamine.
      Analysis of products by mass spectrometry and NMR indicated that the amphDIII
      mutant produced 8-deoxyamphoteronolides A and B. This suggests that glycosylation
      with mycosamine normally precedes C-8 hydroxylation and that formation of the
      exocyclic carboxyl group can occur prior to both these modifications.
      Inactivation of the amphL cytochrome P450 gene led to production of novel
      polyenes with masses appropriate for 8-deoxyamphotericins A and B. These
      compounds retained antifungal activity and may be useful new antibiotics.

PMID- 14700630
TI  - Iteration as programmed event during polyketide assembly; molecular analysis of
      the aureothin biosynthesis gene cluster.
AB  - Analysis of the type I modular polyketide synthase (PKS) involved in the
      biosynthesis of the rare nitroaryl polyketide metabolite aureothin (aur) from
      Streptomyces thioluteus HKI-227 has revealed only four modules to catalyze the
      five polyketide chain extensions required. By heterologous expression of the aur
      PKS cluster, direct evidence was obtained that these modules were sufficient to
      support aureothin biosynthesis. It appears that one module catalyzes two
      successive cycles of chain extension, one of the first examples of a PKS in which
      such iteration or "stuttering" is required to produce the normal polyketide
      product. In addition, lack of a specified loading domain implicates a novel PKS
      priming mechanism involving the unique p-nitrobenzoate starter unit. The 27 kb
      aur gene cluster also encodes a novel N-oxidase, which may represent the first
      member of a new family of such enzymes.

PMID- 14700631
TI  - Generalized RNA-directed recombination of RNA.
AB  - RNA strand exchange through phosphor-nucleotidyl transfer reactions is an
      intrinsic chemistry promoted by group I intron ribozymes. We show here that
      Tetrahymena and Azoarcus ribozymes can promote RNA oligonucleotide recombination
      in either two-pot or one-pot schemes. These ribozymes bind one oligonucleotide,
      cleave following a guide sequence, transfer the 3' portion of the oligo to their
      own 3' end, bind a second oligo, and catalyze another transfer reaction to
      generate recombinant oligos. Recombination is most effective with the Azoarcus
      ribozyme in a single reaction vessel in which over 75% of the second oligo can be
      rapidly converted to recombinant product. The Azoarcus ribozyme can also create a
      new functional RNA, a hammerhead ribozyme, which can be constructed via
      recombination and then immediately promote its own catalysis in a homogeneous
      milieu, mimicking events in a prebiotic soup.

PMID- 14700632
TI  - Control of gene expression with small molecules: biotin-mediated acylation of
      targeted lysine residues in recombinant yeast.
AB  - Chemical inducers of dimerization (CIDs) are powerful tools for controlling
      diverse cellular processes. These small molecules typically form strong
      noncovalent interactions with proteins. We report a related approach involving
      covalent acylation of a specific lysine residue of a target protein by the small
      molecule biotin. To control protein-protein interactions with biotin, the biotin
      protein ligase BirA from E. coli was coexpressed in yeast with a streptavidin
      LexA fusion protein and Avitag or BCCP biotin acceptor peptides fused to the B42
      activation domain. The addition of biotin (10 nM) resulted in BirA-mediated
      biotinylation of the biotin acceptor protein, recruitment to LexA DNA sites, and
      maximal activation of reporter gene expression in this yeast tribrid system. The
      high potency, low toxicity, and low molecular weight of biotin as a covalent CID
      are attractive properties for controlling cellular processes.

PMID- 14700633
TI  - GSK-3-selective inhibitors derived from Tyrian purple indirubins.
AB  - Gastropod mollusks have been used for over 2500 years to produce the "Tyrian
      purple" dye made famous by the Phoenicians. This dye is constituted of mixed
      bromine-substituted indigo and indirubin isomers. Among these, the new natural
      product 6-bromoindirubin and its synthetic, cell-permeable derivative, 6
      bromoindirubin-3'-oxime (BIO), display remarkable selective inhibition of
      glycogen synthase kinase-3 (GSK-3). Cocrystal structure of GSK-3beta/BIO and
      CDK5/p25/indirubin-3'-oxime were resolved, providing a detailed view of
      indirubins' interactions within the ATP binding pocket of these kinases. BIO but
      not 1-methyl-BIO, its kinase inactive analog, also inhibited the phosphorylation
      on Tyr276/216, a GSK-3alpha/beta activation site. BIO but not 1-methyl-BIO
      reduced beta-catenin phosphorylation on a GSK-3-specific site in cellular models.
      BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6
      bromoindirubins thus provide a new scaffold for the development of selective and
      potent pharmacological inhibitors of GSK-3.

PMID- 14700634
TI  - Small molecule modulation of the human chromatid decatenation checkpoint.
AB  - After chromosome replication, the intertwined sister chromatids are disentangled
      by topoisomerases. The integrity of this process is monitored by the chromatid
      decatenation checkpoint. Here, we describe small molecule modulators of the human
      chromatid decatenation checkpoint identified using a cell-based, chemical genetic
      modifier screen. Similar to 1,2,7-trimethylyxanthine (caffeine), these small
      molecules suppress the G(2)-phase arrest caused by ICRF-193, a small molecule
      inhibitor of the enzymatic activity of topoisomerase II. Analysis of specific
      suppressors, here named suptopins for suppressor of Topoisomerase II inhibition,
      revealed distinct effects on cell cycle progression, microtubule stability,
      nucleocytoplasmic transport of cyclin B1, and no effect on the chromatin
      deacetylation checkpoint induced by trichostatin A. The suptopins provide new
      molecular tools for dissecting the role of topoisomerases in maintaining genomic
      stability and determining whether inhibiting the chromatid decatenation
      checkpoint sensitizes tumor cells to chemotherapeutics.

PMID- 14700635
TI  - Molecular cloning and analysis of the ergopeptine assembly system in the ergot
      fungus Claviceps purpurea.
AB  - Claviceps purpurea produces the pharmacological important ergopeptines, a class
      of cyclol-structured alkaloid peptides containing D-lysergic acid. These
      compounds are assembled from D-lysergic acid and three different amino acids by
      the nonribosomal peptide synthetase enzymes LPS1 and LPS2. Cloning of alkaloid
      biosynthesis genes from C. purpurea has revealed a gene cluster including two
      NRPS genes, cpps 1 and cpps 2. Protein sequence data had assigned earlier cpps1
      to encode the trimodular LPS1 assembling the tripeptide portion of ergopeptines.
      Here, we show by transcriptional analysis, targeted inactivation, analysis of
      disruption mutants, and heterologous expression that cpps 2 encodes the
      monomodular LPS2 responsible for D-lysergic acid activation and incorporation
      into the ergopeptine backbone. The presence of two distinct NRPS subunits
      catalyzing formation of ergot peptides is the first example of a fungal NRPS
      system consisting of different NRPS subunits.

PMID- 14700636
TI  - Assembly of the covalent linkage between lipoic acid and its cognate enzymes.
AB  - Lipoic acid is synthesized from octanoic acid by insertion of sulfur atoms at
      carbons 6 and 8 and is covalently attached to a pyruvate dehydrogenase (PDH)
      subunit. We show that sulfur atoms can be inserted into octanoyl moieties
      attached to a PDH subunit or a derived domain. Escherichia coli lipB mutants grew
      well when supplemented with octanoate in place of lipoate. Octanoate growth
      required both lipoate protein ligase (LplA) and LipA, the sulfur insertion
      protein, suggesting that LplA attached octanoate to the dehydrogenase and LipA
      then converted the octanoate to lipoate. This pathway was tested by labeling a
      PDH domain with deuterated octanoate in an E. coli strain devoid of LipA
      activity. The labeled octanoyl domain was converted to lipoylated domain upon
      restoration of LipA. Moreover, octanoyl domain and octanoyl-PDH were substrates
      for sulfur insertion in vitro.

PMID- 14700637
TI  - Regulating cell surface glycosylation by small molecule control of enzyme
      localization.
AB  - Cell surface carbohydrates mediate interactions between the cell and its
      environment. Glycosyltransferases responsible for synthesis of cell surface
      oligosaccharides are therefore essential administrators of cellular
      communication. These enzymes often comprise large families. Redundancy of related
      family members and embryonic lethality both complicate genetic methods for
      deconvoluting functions of glycosyltransferases. We report a chemical method in
      which the activity of an individual glycosyltransferase is controlled by a small
      molecule. The approach exploits the requirement of Golgi localization, a common
      feature of glycosyltransferase superfamily members. In our approach, the
      glycosyltransferase is separated into two domains, one that determines
      localization and one responsible for catalysis. Control of enzyme activity is
      achieved using a small molecule to regulate association of the two domains. We
      used this method to regulate production of sialyl Lewis x by alpha1,3
      fucosyltransferase VII in living cells.

PMID- 14700638
TI  - Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and
      management.
AB  - PURPOSE: To update clinical information about ocular toxoplasmosis. Part II
      reviews the spectrum of disease manifestations and factors that influence
      severity of disease. Implications for disease management are discussed. DESIGN:
      Literature review. METHODS: Selected articles from the medical literature,
      information from several recent scientific meetings, and the author's personal
      experiences were reviewed critically in preparation for the LX Edward Jackson
      Memorial Lecture. RESULTS: The appearance of toxoplasmic retinochoroiditis
      lesions varies with duration of active retinal infection and intensity of
      inflammation. Severe ocular disease occurs in immunocompromised hosts. Older
      patients who are recently infected with Toxoplasma gondii may have a higher
      prevalence of ocular involvement and more severe ocular disease because of
      altered host defenses. Most disease-producing isolates of T. gondii belong to one
      of three clonal lineages (types I, II, III); type I has been associated with
      severe disease in both animals and human beings. Many observational studies
      suggest a benefit of short-term antimicrobial therapy for toxoplasmic
      retinochoroiditis in immunocompetent patients, although the efficacy of these
      treatments has not been proven in randomized clinical trials. Intermittent
      trimethoprim/sulfamethoxazole treatment was associated with fewer recurrences
      than placebo during a 20-month randomized clinical trial. CONCLUSIONS: Variations
      in disease characteristics may be related to host, parasite, or environmental
      factors. The genotype of the infecting parasite appears to be an important
      determinant of disease severity in immunocompetent patients. Secondary
      prophylaxis may reduce the rate of recurrences in high-risk patients. A better
      clinical understanding of ocular toxoplasmosis can lead to more effective
      prevention and treatment strategies.

PMID- 14700639
TI  - Preimplantation genetic diagnosis for retinoblastoma: the first reported
      liveborn.
AB  - PURPOSE: To develop an accurate mutation analysis procedure for retinoblastoma
      gene (RB1) mutation, which is sensitive at the single-cell level, and to use in
      vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) to achieve
      pregnancies without retinoblastoma. DESIGN: Case report. METHODS: Twelve day 3
      embryos, obtained by IVF with intracytoplasmic sperm injection, underwent single
      cell DNA testing via polymerase chain reaction and restriction enzyme analysis to
      detect the presence of a paternal RB1 mutation. Embryos were diagnosed as being
      unaffected and were transferred to the uterus on day 5. MAIN OUTCOME MEASURES:
      Achieving a healthy pregnancy and delivery, assessed by clinical presentation,
      fundus photography, and RB1 molecular analysis. RESULTS: A singleton pregnancy
      was achieved, and a child without retinoblastoma was born. The absence of the
      paternal RB1 mutation was confirmed on a sample of peripheral blood from the
      newborn. CONCLUSIONS: We are first to report a successful human liveborn,
      delivered after IVF with preimplantation genetic diagnosis for retinoblastoma.
      The successful result indicates that preimplantation genetic diagnosis exists for
      this genetic disease and may represent a viable alternative to prenatal diagnosis
      with the subsequent option of terminating an affected pregnancy.

PMID- 14700640
TI  - The impact of echography on evaluation and management of posterior segment
      disorders.
AB  - PURPOSE: To investigate the impact on patient management of posterior segment
      echographic evaluation at an academic institution. DESIGN: Retrospective,
      noncomparative, consecutive case series. METHODS: Records were reviewed of all
      patients evaluated for the first time with ocular echography for posterior
      segment evaluation at Bascom Palmer Eye Institute between September 2000 and
      August 2001. Patients with prior posterior segment echography, intraocular
      tumors, or suspected optic nerve or orbital disease were excluded. An "impactful"
      echographic evaluation was defined as an evaluation that confirmed the diagnosis
      and management plan. A "pivotal" evaluation was defined as an evaluation that
      either (1) made or subclassified the diagnosis or (2) established or changed the
      management plan or both. Main outcome measures include proportions of impactful
      and pivotal echographic evaluations and factors associated with pivotal
      evaluations. RESULTS: The study included 154 eyes of 143 patients. The requesting
      physician was a retina fellowship-trained faculty member in 55 cases (36%), a
      nonretina faculty member in 22 (14%), a fellow in 9 (6%), and a resident in 68
      (44%). Reasons for obtaining echography included evaluation for retinal tear or
      detachment in 83 eyes (54%), evaluation for posterior segment disease (for
      example, before cataract extraction) in 40 (26%), evaluation for endophthalmitis
      in 10 (7%), evaluation for intraocular foreign body in 8 (5%), characterization
      of choroidal detachment in 4 (2%), and other in 9 (6%). Echography confirmed the
      suspected diagnosis and pre-echography management plan in 128 eyes (83%).
      Echography made or subclassified the diagnosis in 20 eyes (13%) and established
      or changed the management plan in 12 eyes (8%). Accounting for definitional
      overlaps, echography was pivotal in 22 eyes (14%). Significant predictors of a
      pivotal evaluation or an evaluation that affected the management plan include a
      retina faculty member as the requesting physician (P =.003), lack of a management
      plan before echography (P <.001), and certain reasons for obtaining echography
      (for example, to rule out retinal tear or detachment and to rule out intraocular
      foreign body; P =.032). The final clinical or pathologic diagnosis confirmed the
      echographic diagnosis in 148 eyes (96%). CONCLUSIONS: Posterior segment
      echography may be a very useful diagnostic tool. Its value may be optimized in
      certain subsets of patients. Considerations such as these may contribute to more
      cost-effective allocation of resources.

PMID- 14700641
TI  - Frequency and predictors of glaucoma after pediatric cataract surgery.
AB  - PURPOSE: To determine the frequency of and identify predictors of chronic
      glaucoma after pediatric cataract surgery. DESIGN: Interventional case series.
      METHODS: Retrospective review at an eye hospital identified 570 eyes among 322
      patients who underwent limbal-approach surgery without intraocular lens
      implantation at age <or=16 years for cataract unassociated with other ocular
      anomalies aside from microcornea. Patients had a minimum of 5 years'
      postoperative follow-up, which included intraocular pressure measurement. The
      outcome measure was the presence or absence of postcataract surgery glaucoma,
      defined as intraocular pressure >or=26 mm Hg, as measured on at least two
      occasions. RESULTS: Mean follow-up was 9.0 +/- 3.1 years (median, 8.1 years;
      range, 5.0-18.3 years). Glaucoma developed in 118 of 570 patients' eyes (21%),
      including 101 of 272 (37%) undergoing surgery at <or=9 months of age and 17 of
      298 (6%) undergoing surgery thereafter. Multivariable Cox proportional hazards
      regression analysis with adjustment for potential intrasubject correlation
      identified surgery at <or=9 months of age (hazard ratio [HR], 3.8; 95% confidence
      interval [CI], 1.8-7.7; P <.001), secondary membrane surgery (HR, 2.6; 95% CI,
      1.3-5.3; P =.006), microcornea (HR, 1.9; 95% CI, 1.2-3.1; P =.008), and primary
      posterior capsulotomy/anterior vitrectomy (HR, 10.7; 95% CI, 1.4-80.6; P =.02) as
      predictors of glaucoma. CONCLUSIONS: Chronic glaucoma is common after cataract
      surgery performed at or before, but not after, a certain age in childhood. The
      data suggest that this age threshold is 9 months, but a true threshold occurring
      at a somewhat later age cannot be fully excluded.

PMID- 14700642
TI  - Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture
      proven cases.
AB  - PURPOSE: To investigate the spectrum of organisms causing culture-proven
      endophthalmitis and their sensitivities to commonly used antimicrobial agents.
      DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: Medical
      records were reviewed of all patients with culture-proven endophthalmitis at a
      single institution between January 1, 1996, and December 31, 2001.
      Endophthalmitis categories included postoperative, posttraumatic, endogenous, and
      miscellaneous (for example, keratitis). The outcome measures included
      intravitreal isolates identified, antibiotic sensitivities, and category of
      endophthalmitis. RESULTS: In all, 313 organisms were isolated from 278 patients
      during the study interval. The most common organisms identified were
      Staphylococcus epidermidis in 27.8% (87/313), Streptococcus viridans group in
      12.8% (40/313), other coagulase-negative staphylococci in 9.3% (29/313),
      Staphylococcus aureus in 7.7% (24/313), and Propionibacterium acnes in 7.0%
      (22/313). Overall, 246 of 313 (78.5%) isolates were gram-positive organisms, 37
      (11.8%) were gram-negative organisms, and 27 (8.6%) were fungi. For gram-positive
      organisms, sensitivities were the following: vancomycin 100%, gentamicin 78.4%,
      ciprofloxacin 68.3%, ceftazidime 63.6%, and cefazolin 66.8%. For gram-negative
      organisms, sensitivities were the following: ciprofloxacin 94.2%, amikacin 80.9%,
      ceftazidime 80.0%, and gentamicin 75.0%. Fungal isolates were Candida species
      (9/313), Aspergillus species (9/313), and other molds (9/313). Among the
      endophthalmitis categories, the most frequent organisms were the following: (1)
      acute-onset postoperative: S epidermidis, 46.9%; (2) delayed-onset postoperative:
      S epidermidis, 22.7%; (3) delayed-onset bleb-associated: fastidious gram-negative
      rods, 20.4%; (4) posttraumatic: S epidermidis, 20.8%; (5) endogenous: Aspergillus
      species, 20.8%; and (6) miscellaneous: molds (other), 36.4%. CONCLUSIONS: In
      considering antibiotic treatment of endophthalmitis, it is important to recognize
      that no single antibiotic provided coverage for all of the microbes isolated from
      eyes with endophthalmitis. Combination therapy is recommended as the initial
      empiric treatment of suspected bacterial endophthalmitis. Appropriate history and
      characteristic clinical features may justify the use of initial antifungal
      agents. Knowledge of the most frequent causative organisms in various categories
      will help direct appropriate initial therapy.

PMID- 14700643
TI  - Shifting trends in in vitro antibiotic susceptibilities for common ocular
      isolates during a period of 15 years.
AB  - PURPOSE: To assess the in vitro susceptibility of the most common ocular
      bacterial isolates to several antibiotics and verify changing trends in the
      antibiotic susceptibility in a 15-year period. DESIGN: Experimental study.
      METHODS: All cultures positive for Staphylococcus aureus, coagulase-negative
      Staphylococcus (CNS), Streptococcus sp, and Pseudomonas sp in conjunctival (n =
      4,585) and corneal (n = 3,779) samples from patients seen at the Federal
      University of Sao Paulo from 1985 to 2000 were evaluated. Cultures were performed
      in liquid and solid media, and susceptibility tests were done to amikacin,
      gentamicin, neomycin, tobramycin, ciprofloxacin, norfloxacin, ofloxacin,
      cephalothin, and chloramphenicol. RESULTS: Amikacin and neomycin showed an
      improvement of their sensitivity during the study period (88%-95% and 50%-85%,
      respectively) for corneal and conjunctival samples. Gentamicin and tobramycin
      revealed a decrease of sensitivity in time, from 95% to less than 80% in corneal
      and conjunctival samples. Ciprofloxacin, norfloxacin, and ofloxacin had good
      sensitivity to all evaluated bacteria, better in conjunctiva (95%) than in cornea
      (90%). Sensitivity of S. aureus to cephalothin decreased during the study but was
      still 98% for CNS. Chloramphenicol had good sensitivity to S. aureus (85% in
      corneal and 92%in conjunctival samples), CNS (87% and 88.5%), and Streptococcus
      sp (95% and 96%). CONCLUSIONS: Gentamicin, tobramycin, and cephalothin decreased
      their in vitro susceptibility to all tested pathogens. The fluoroquinolones
      remained a good choice in the treatment of ocular infections, with high suscep
      tibility to all pathogens tested. Chloramphenicol also revealed an increase in
      its susceptibility to all bacteria evaluated.

PMID- 14700644
TI  - The effect of punctal occlusion on wavefront aberrations in dry eye patients
      after laser in situ keratomileusis.
AB  - PURPOSE: To compare the wavefront aberrations in post-laser in situ
      keratomileusis (LASIK) dry eye patients before and after punctal occlusion.
      DESIGN: Prospective, comparative, nonrandomized study. METHODS: Wavefront
      aberrometry was performed on 16 eyes of eight patients with dry eyes after LASIK
      surgery. Wavefront measurements were taken before and 1 month after punctal plug
      placement and compared with 10 eyes of post-LASIK patients without clinically dry
      eyes measured twice 1 month apart. Student t tests were used to assess the
      statistical significance of differences between pre- and post-punctal plug
      measurements. RESULTS: Punctal occlusion in the post-LASIK dry eye patients
      significantly reduced total, lower, and higher order wavefront aberrations by 47%
      to 63% (P <.01). Among higher-order aberrations, there were significant
      reductions in coma and spherical aberration but not in trefoil, after punctal
      occlusion. The reduction of wavefront aberrations by punctal occlusion in post
      LASIK dry eye patients resulted in a significant improvement in quantitative
      visual acuity assessed using an Early Treatment of Diabetic Retinopathy Study
      chart and in subjective qualitative vision, confirmed by convolutional analysis
      using image simulation. No statistically significant differences in any of these
      metrics were found in the post-LASIK control group without clinically dry eyes
      measured twice at a similar time interval. CONCLUSIONS: Wavefront aberrometry
      provides a useful, objective assessment of post-LASIK dry eye patients before and
      after punctal plug placement. Aggressive treatment of dry eyes may be important
      before obtaining wavefront measurements that serve as the basis for planning
      refractive corneal laser treatments and retreatments.

PMID- 14700645
TI  - Oxidative stress markers in aqueous humor of glaucoma patients.
AB  - PURPOSE: Oxidative stress and antioxidant status in eye tissues may be associated
      with glaucomatous damage. The aim of this study was to establish the antioxidant
      status of aqueous humor of patients with primary open-angle glaucoma. For this
      purpose the authors measured the total reactive antioxidant potential (TRAP) and
      the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase,
      and glutathione peroxidase. DESIGN: Case control study. METHODS: Aqueous humor
      was obtained at the time of surgery from 24 patients with glaucoma and 24
      cataract patients; TRAP was measured by chemiluminescence. Activities of the
      antioxidant enzymes were measured spectrophotometrically. Superoxide dismutase
      activity was determined by inhibition of the rate of adrenochrome formation at
      480 nm. Catalase activity was evaluated by decrease of H(2)O(2) absorbance at 240
      nm. Glutathione peroxidase (GPx) activity was determined following nicotinamide
      adenine dinucleotide phosphate oxidation at 340 nm. RESULTS: Total reactive
      antioxidant potential value of the cataract group was 124 +/- 5 micromol/l
      Trolox. This value was significantly decreased, by 64%, in glaucoma patients. An
      increase of 57% in SOD activity was observed in glaucoma patients when compared
      with cataract patients (41.7 +/- 2.7 U SOD/ml). Glutathione activity was
      threefold higher in glaucoma patients than in the cataract group (6.1 +/- 0.6
      U/ml). No significant changes were found in catalase levels. CONCLUSIONS:
      Oxidative stress may lead to an induction of antioxidant enzymes and contribute
      to TRAP decrease. Superoxide dismutase, GPx activities, and TRAP may be useful
      oxidative stress markers in aqueous humor of glaucoma patients.

PMID- 14700646
TI  - Adult-onset acquired oculomotor nerve paresis with cyclic spasms: relationship to
      ocular neuromyotonia.
AB  - PURPOSE: To describe the characteristics and significance of acquired oculomotor
      nerve paresis with cyclic spasm. METHOD: Retrospective case series of two
      patients with a history of previous skull base irradiation for intracranial tumor
      who developed double vision and were found to have oculomotor nerve paresis with
      cyclic spasm. Both patients underwent a complete neuroophthalmologic assessment,
      including testing of eyelid position, pupillary size and reactivity, and ocular
      motility and alignment during both the paretic and spastic phases of the
      condition. RESULTS: Both patients developed unilateral lid retraction and
      ipsilateral esotropia with limitation of abduction during the spastic phase of
      the cycle, with ipsilateral ptosis, exotropia, and variable limitation of
      adduction during the paretic phase. The cycles were continuous and were not
      induced or altered by eccentric gaze. CONCLUSIONS: Cyclic oculomotor nerve
      paresis with spasms may occur years after irradiation of the skull base. This
      condition is different from the more common ocular motor disturbance that occurs
      in this setting-ocular neuromyotonia. However, in view of the similarity between
      these two disorders, it seems likely that they are caused by a similar peripheral
      mechanism.

PMID- 14700647
TI  - Visual function more than 10 years after optic neuritis: experience of the optic
      neuritis treatment trial.
AB  - PURPOSE: To assess visual function more than 10 years after an episode of optic
      neuritis in patients enrolled in the Optic Neuritis Treatment Trial. DESIGN:
      Longitudinal follow-up of a randomized clinical trial. METHODS: Vision testing
      included measures of visual acuity, contrast sensitivity, and visual field.
      Quality of life was assessed with the National Eye Institute Visual Function
      Questionnaire. RESULTS: Examinations were completed on 319 patients. In most
      patients, visual function test results in the eyes that experienced optic
      neuritis at study entry ("affected eyes") were normal or only slightly abnormal
      after 9.9 to 13.7 years. Visual acuity in the affected eyes was >or=20/20 in 74%,
      20/25 to 20/40 in 18%, <20/40 to 20/200 in 5%, and <20/200 in 3%. On average,
      visual function was worse in patients with multiple sclerosis (MS) than in those
      without MS. Recurrent optic neuritis in either eye occurred in 35% of patients.
      Such attacks were more frequent in patients with MS (P <.001). The National Eye
      Institute Visual Function Questionnaire scores were lower when visual acuity was
      abnormal and when MS was present. CONCLUSIONS: Most patients retained good to
      excellent vision more than 10 years after an attack of optic neuritis.
      Recurrences were more frequent in patients with MS.

PMID- 14700648
TI  - Association of neovascular age-related macular degeneration and
      hyperhomocysteinemia.
AB  - PURPOSE: To assess the relationship between plasma homocysteine levels and
      exudative neovascular age-related macular degeneration (AMD). DESIGN: Cross
      sectional study. METHODS: A prospective comparative cross-sectional study was
      conducted in outpatient ophthalmology clinics in a university-affiliated medical
      institution. The cohort consisted of 59 patients (25 male, 34 female) with a mean
      age of 78 years (standard deviation [SD] = 8.4) with neovascular AMD who were
      candidates for photodynamic treatment. Patients were compared for plasma
      homocysteine levels with 58 patients who had dry AMD (24 male, 34 female) with a
      mean age of 76.3 years (SD = 8.4) and with a control group of 56 age-matched
      subjects (27 male, 29 female), with a mean age of 77.3 years (SD = 8.2). A 3-ml
      venous blood sample was obtained from each participant after an 8-hour fast.
      Levels of plasma homocysteine were measured by high performance liquid
      chromatography. The main outcome measure was hyperhomocysteinemia, defined as a
      plasma homocysteine level above 15 micromol/l. RESULTS: Homocysteine levels were
      higher by 27.9% in the neovascular AMD than in the dry AMD group, and by 21.9%
      than in the control group (P <.02). Hyperhomocysteinemia was found in 44.1% of
      the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group
      (P =.011). CONCLUSIONS: This study suggests an association between an elevated
      plasma level of homocysteine and exudative neovascular AMD but not dry AMD.

PMID- 14700649
TI  - Optical coherence tomography in the evaluation of retinal changes associated with
      suspicious choroidal melanocytic tumors.
AB  - PURPOSE: Subretinal fluid (SRF) is a strong risk factor for growth of choroidal
      melanocytic tumors. However, subtle SRF can be difficult to assess clinically and
      to distinguish from chronic retinal changes overlying a dormant lesion. This
      study investigates optical coherence tomography (OCT) in evaluating SRF in
      suspicious choroidal melanocytic tumors. DESIGN: Interventional case series.
      METHODS: Review of 33 patients with untreated choroidal melanocytic tumors who
      underwent OCT for suspicion of subtle SRF. Fluorescein angiography was performed
      in 26 of the patients. The main outcome was tumor growth. RESULTS: No retinal
      separation was found in 12 tumors, of which 1 (8%) grew on follow-up and 3 (25%)
      were treated. Chronic retinal changes (localized retinal separation with retinal
      atrophy or intraretinal cysts) were found in nine tumors: one (11%) grew on
      follow-up and none were treated. Active SRF (localized retinal separation with
      normal retinal appearance) was found in 12 tumors: 6 (50%) grew on follow-up, and
      7 (58%) were treated. The active OCT pattern was associated with fluorescein
      angiography hotspots (P =.041), documented tumor growth (P =.033), and tumor
      treatment (P =.014), and inversely associated with drusen (P =.024), atrophic
      retinal pigment epithelium changes surrounding the tumor (P =.048), and
      intraretinal cysts by OCT (P =.002). CONCLUSIONS: Optical coherence tomography is
      useful in distinguishing active subretinal fluid from chronic retinal changes
      overlying a choroidal melanocytic tumor. Optical coherence tomography findings
      may have predictive value in identifying tumors that are likely to grow and
      require treatment.

PMID- 14700650
TI  - Complications of hydrogel explants used in scleral buckling surgery.
AB  - PURPOSE: To report a group of patients with symptoms of pain, strabismus,
      sensation of orbital fullness, and presence of a subconjunctival mass many years
      after successful scleral buckling surgery using hydrogel explants. DESIGN: We
      present an interventional consecutive case series of patients who underwent
      scleral buckling surgery using hydrogel explants from 4 to 14 years before onset
      of clinical symptoms. SETTING: This is a retrospective, multicenter clinical
      study. PATIENT POPULATION: 17 eyes of 15 patients presented with this disorder.
      All patients were examined; Snellen acuity, ocular motility, tonometry, slit
      lamp, and fundus examination were recorded. Two patients underwent either
      computed tomography or magnetic resonance imaging. Removal of the hydrogel
      explant was attempted in all patients. Removal of the buckle was technically
      difficult; the hydrogel material was fragile and fragmented when handled.
      RESULTS: All patients had prompt relief of pain and discomfort. Ocular motility
      and diplopia were greatly improved. Extraocular muscle surgery was not required
      in any case. Three eyes had intraoperative eye wall perforation. One eye
      developed postoperative bacterial endophthalmitis. Five eyes had recurrence of
      retinal detachment. One eye had additional complications of corneal edema and
      glaucoma. CONCLUSIONS: Patients who develop this clinical condition should be
      considered for removal of the hydrogel scleral buckle. Early recognition of this
      condition may prevent serious complications associated with delayed removal.

PMID- 14700651
TI  - Lacrimal canalicular bypass surgery with the Lester Jones tube.
AB  - PURPOSE: To analyze outcomes of lacrimal bypass surgery with the Lester Jones
      tube and to determine the level of patient satisfaction. DESIGN: Interventional
      case series. METHODS: We retrospectively analyzed the outcomes of 49 patients (42
      patients) who underwent conjunctivodacryocystorhinostomy between 1984 and 2002.
      Data were obtained from medical records, semistructured phone interviews, and
      written questionnaires. RESULTS: The causes of lacrimal obstruction were
      idiopathic and trauma, congenital agenesis, infection, inflammation, herpes,
      basal cell carcinoma, radiation therapy, penicillin-induced Steven-Johnsons
      syndrome, systemic chemotherapy, and facial nerve palsy. Patients had undergone
      previous failed lacrimal surgery in 21% of cases. Complete or significant
      improvement of epiphora was achieved in 94% of cases. Best results were obtained
      for trauma and herpetic obstruction. Complications were frequent and included
      extrusion, recurrent extrusion, malposition, obstruction, discomfort, infection,
      and diplopia. Of the 32 patients who were interviewed, 70% were satisfied with
      the result, 35% reported tube maintenance to be troublesome, and all patients
      were pleased with the esthetics of the Jones tube. CONCLUSIONS:
      Conjunctivodacryocystorhinostomy with the insertion of a Jones tube can be
      expected to improve epiphora significantly in most cases and remains the standard
      treatment for canalicular obstruction. Complications occur in most cases,
      requiring replacement, repositioning, and cleaning of the tube by the
      ophthalmologist over an indefinite period of time. Despite frequent
      complications, patients will usually be satisfied if they obtain a comfortable,
      dry eye. If, however, a completely dry eye is not achieved, frequent
      complications may contribute to patient dissatisfaction.

PMID- 14700652
TI  - Corneal epitheliopathy of dry eye induces hyperesthesia to mechanical air jet
      stimulation.
AB  - PURPOSE: To evaluate corneal sensation in different groups: normal subjects, dry
      eye patients, and patients with and without dry eye after laser in situ
      keratomileusis (LASIK) using the modified Belmonte gas esthesiometer. DESIGN: A
      retrospective, clinic-based, case-control study. METHODS: We evaluated 20 normal
      subjects, 20 dry eye patients, 20 post-LASIK patients without dry eye, and six
      post-LASIK patients with dry eye. The corneal sensation was measured with the
      modified Belmonte gas esthesiometer that uses two different stimuli to assess
      mechanical and polymodal receptors on the corneal surface. Mechanoreceptors were
      assessed by 2-second pulsed air jets of variable intensity. Polymodal receptors
      were measured by stimulating the corneal with 2-second pulsed air jets of varying
      concentrations of CO(2), a gas that is converted to carbonic acid on contact with
      the corneal surface. The main outcome measure was determining corneal sensation.
      RESULTS: The mean +/- standard deviation (+/- SD) age was similar in all groups.
      The mean mechanical threshold was 61.50 +/- 20.07 ml/min in the normal group (n =
      20), 34.60 +/- 21.09 ml/min in the dry group (n = 20, P <.05 vs normal), 99.50 +/
      47.40 ml/min in the post-LASIK group (n = 20, P <.01 vs normal), and 50.00 +/-
      15.49 ml/min in the post-LASIK patients with keratitis sicca (n = 06, P <.05 vs
      post-LASIK). The percentage of CO(2) to elicit discomfort was similar in all
      groups (P >.05). No sex-related differences were noted (P >.05). There was a
      significant inverse correlation between the threshold of mechanical stimulation
      and the severity of corneal fluorescein staining. CONCLUSIONS: The Belmonte
      modified noncontact esthesiometer is a sophisticated instrument that can assess
      different types of corneal sensory receptors. Patients with dry eye were
      hypersensitive to the air jet stimulus of this instrument, and this appears to be
      due to altered corneal epithelial barrier function. Profound hypoesthesia was
      observed after LASIK and similar to dry eye, post-LASIK patients with dry eye
      were sensitized. These findings provide new insight into the hypersensitivity to
      environmental stresses, particularly air drafts experienced by dry eye patients.

PMID- 14700653
TI  - Evaluation of the tear film stability after laser in situ keratomileusis using
      the tear film stability analysis system.
AB  - PURPOSE: To evaluate the tear film stability of patients before and after laser
      in situ keratomileusis (LASIK) using the tear film stability analysis system
      (TSAS). DESIGN: Prospective observational case series. METHODS: New
      videokeratography software for a topographic modeling system (TMS-2N) was
      developed that can automatically capture consecutive corneal surface images every
      second for 10 seconds. Thirty-four subjects (64 eyes) who underwent myopia LASIK
      were enrolled in this study. All subjects were examined with the new system
      before LASIK and at 1 week, 1 month, 3 months, and 6 months after the surgery.
      Corneal topographs were analyzed for tear breakup time (TMS breakup time) and
      breakup area (TMS breakup area). Based on pre-LASIK TSAS analysis, subjects were
      separated into normal and abnormal TSAS value groups. The criteria for the normal
      group were either TMS breakup time more than 5 seconds or TMS breakup area less
      than 0.2. The percentage of the occurrence of superficial punctuate keratitis was
      compared between the two groups with regard to subject's dry eye signs and
      symptoms. RESULTS: Tear film stability decreased significantly during the early
      period after LASIK, as indexed by decreased TMS breakup time and increased TMS
      breakup area. Tear film instability resolved at 6 months after surgery. Before
      LASIK, 22 subjects (43 eyes) had normal TSAS evaluation and 12 subjects (21 eyes)
      were abnormal. After LASIK, among normal TSAS value eyes, 8 of 43 (18.6%) eyes
      developed superficial punctuate keratitis. In sharp contrast, 14 of 21 (66.7%)
      eyes in the abnormal group displayed superficial punctuate keratitis, correlating
      well with the patients' dry eye symptoms. The difference in the presence of
      superficial punctuate keratitis after LASIK between normal and abnormal TSAS
      value groups was statistically significant (P <.001). Subjects with abnormal TSAS
      evaluation also displayed resistance to dry eye treatment and had extended period
      of recovery. CONCLUSIONS: Tear film stability analysis can be a useful means for
      screening LASIK candidates before surgery and for prognosticating dry eye
      symptoms thereafter.

PMID- 14700654
TI  - Muscular bridge between the inferior oblique and inferior rectus muscles.
AB  - PURPOSE: In this study, we aimed to investigate the muscular bridge between the
      inferior oblique (IO) and inferior rectus (IR) muscles of the eye. DESIGN: Cohort
      study. METHODS: The orbits of sixty intact cadavers with no history of eye muscle
      or orbital disorders during life were carefully dissected to expose the muscular
      bridge between the IO and IR muscles. Numbers of the bridges, their length and
      width were recorded. RESULTS: We observed muscular bridge between IO and IR
      muscles in 6.6% of 60 orbits. They originated from the lateral side of the IR
      muscle, and joined to posteromedial side of the IO muscle. Mean length and width
      were 14.2 +/- 6.3 and 1.3 +/- 0.2 mm, respectively. CONCLUSIONS: Muscular bridges
      were found in 6.6% of orbits dissected. We conclude that muscular bridges are
      important due to potential cause of failed IO or IR muscles surgery. In this
      respect, before surgery of the extraocular muscles, the muscular bridges should
      be kept in mind and demonstrated by computed tomography or magnetic resonance
      imaging in transverse, sagittal, and coronal planes.

PMID- 14700655
TI  - Transposition of the anterior superior oblique insertion as a treatment for
      excyclotorsion induced from limited macular translocation.
AB  - PURPOSE: To evaluate the transposition of the anterior superior oblique insertion
      as a treatment for cyclovertical diplopia accompanied by an awareness of tilted
      image perceived with the affected eye induced from limited macular translocation
      (LMT). DESIGN: Observational case series. METHODS: Transposition of the anterior
      part of the superior oblique tendon combined with or without vertical muscle
      surgery on the affected eye was retrospectively studied in seven patients.
      Clinical outcome was assessed for binocular and monocular vision. A successful
      result was defined as restoration of single binocular vision (SBV) at distance
      and near examined with the Bagolini test with disappearance of a tilted image
      perceived in the affected eye. RESULTS: Six of seven patients (86%) became
      unaware of tilted image, and three patients (43%) obtained successful results
      after the strabismus surgery. Of these three patients with successful results,
      one (33%) patient recognized metamorphopsia, whereas two (67%) of the three
      patients with unfavorable results reported metamorphopsia. Patients with
      successful results showed a visual acuity of 20/25 or better in the affected eye
      and a significantly smaller difference in visual acuity between the two eyes than
      those patients with unfavorable surgical results (0.133 logarithm of the minimal
      angle of resolution for SBV(+) vs 0.675 logarithm of the minimal angle of
      resolution for SBV(-); P =.0255). CONCLUSIONS: The relatively low success for
      restoration of SBV indicates that strabismus surgery is recommended for patients
      whose difference in visual acuity between the two eyes is small and who have a
      high level visual acuity of the affected eye.

PMID- 14700656
TI  - The monocular vertical prism dissociation test.
AB  - PURPOSE: To determine if the monocular vertical prism dissociation test can
      differentiate between organic and nonorganic visual loss. DESIGN: A prospective,
      single-masked observational study. METHODS: Three institutional neuro
      ophthalmology practices. Group 1 consisted of 30 normal controls. Group 2
      included 30 patients with known organic visual loss. Group 3 contained 35
      patients with suspected nonorganic monocular visual loss. Participants were asked
      to describe what they saw while viewing a single Snellen letter when a 4-prism
      diopter base-down prism was placed in front of their better eye. Outcome was
      measured by whether the participant sees one or two letters with the prism in
      place. RESULTS: Vision-appropriate results were given by all members of Group 1
      (two images) and by all members of Group 2 (one image). Two images were seen by
      31 of 35 members of Group 3, indicating nonorganic visual loss. The other 4
      subjects in Group 3 saw one image; each was subsequently found to have occult
      pathology. CONCLUSION: The vertical prism test quickly differentiates organic
      from nonorganic monocular visual acuity loss.

PMID- 14700657
TI  - Ocular rosacea in childhood.
AB  - PURPOSE: To describe the clinical characteristics and treatment response of
      ocular rosacea in the pediatric population. DESIGN: Retrospective case series.
      METHODS: The clinic charts of consecutive pediatric cases of ocular rosacea were
      evaluated over a 34-month period. Minimal diagnostic inclusion criteria were the
      presence of posterior eyelid inflammation including meibomian gland inspissation
      and lid margin telangiectasis, in conjunction with conjunctival injection or
      episcleritis. RESULTS: Six patients ranged from 3 to 12 years of age at
      presentation. All shared a long history of ocular irritation and photophobia.
      Five patients (83%) were female and had bilateral involvement. Eyelid
      telangiectases and meibomian gland disease were present in all cases. Three
      patients (50%) had sterile corneal ulcers. Only two patients (33%) had cutaneous
      involvement at the time of diagnosis. All patients experienced significant
      improvement with a combination of oral antibiotics (doxycycline or erythromycin),
      with or without topical antibiotics (erythromycin or bacitracin) or topical
      steroids (fluorometholone). CONCLUSION: Ocular rosacea in children may be
      misdiagnosed as viral or bacterial infections. Unlike in adults, associated
      cutaneous changes are uncommon. Most disease is bilateral, although involvement
      may be asymmetric. Response to conventional treatment is excellent, although long
      term treatment may be necessary to prevent relapses.

PMID- 14700658
TI  - Impact of cataract surgery on the visual ability of the very old.
AB  - PURPOSE: To compare the functional outcome of cataract surgery in terms of visual
      ability between patients ages younger than 84 years, 85 to 89 years, and 90+
      years. Survival time will be estimated at 4 years. DESIGN: Population-based,
      observational case series. METHODS: We prospectively evaluated elderly cataract
      patients' self-assessed visual ability regarding reading, TV viewing, orientation
      ability, activities of daily life, satisfaction, and visual acuity (VA) before
      and approximately 3 months after cataract surgery. All patients operated on
      during a 1-year period from our geographically defined admitting area that
      participated with a questionnaire were included (n = 837). Survival was checked
      after 4 years. RESULTS: Before surgery, the most elderly were significantly more
      dissatisfied with their visual function (P =.007). Seventy-six percent of 85+
      improved their subjective ability to read, and two-thirds of those unable to read
      newspaper print were able to read after surgery. A total of 79% of 90+
      experienced improved postoperative ability to manage their daily lives. Best
      corrected VA (BCVA) improved in 94% (90+ years of age), 90% (85 to 89 years of
      age), and 97% (younger than 84 years of age), respectively. After surgery, VA was
      significantly worse with increasing age, also after adjustment for ocular
      comorbidity (P <.0001). Patients with a BCVA improvement of less than 0.3
      logarithm of the minimal angle of resolution units, patients with comorbidity,
      and patients aged 90+ had approximately 3 times the odds of being dissatisfied
      with vision after surgery. A total of 43% of 90+ years and 62% of 85 to 89 years
      were alive 4 years after surgery. CONCLUSIONS: Most patients aged 85 and older
      had improved visual ability, acuity, and satisfaction after cataract surgery. In
      terms of visual function, surgery of significant cataracts in the very old is
      beneficial also when life expectancy is taken in account.

PMID- 14700659
TI  - Optical coherence tomography to detect and manage retinal disease and glaucoma.
AB  - PURPOSE: To review basic principles of optical coherence tomography, and to
      describe its use in the diagnosis and management of retinal diseases and
      glaucoma. DESIGN: Perspective. METHODS: Literature review. RESULTS: Optical
      coherence tomography is a noninvasive imaging technique that has been used
      increasingly to diagnose and manage a variety of retinal diseases and glaucoma.
      Optical coherence tomography (OCT) is based on the principal of Michelson
      interferometry. Interference patterns produced by low coherence light reflected
      from retinal tissues and a reference mirror are processed into an "A-scan"
      signal. Multiple A-scan signals are aligned to produce a two-dimensional image
      that can be thought of as a form of "in vivo histology." Optical coherence
      tomography has been used to identify macular holes, to differentiate macular
      holes from simulating lesions, to identify lamellar macular holes, macular cysts,
      vitreomacular traction, subretinal fluid, pigment epithelial detachment, and
      choroidal neovascularization. It can be used to identify and quantify macular
      edema, and to measure retinal thickness changes in response to therapy. Macular
      thickness measurements determined by OCT correlate well with visual acuity and
      with leakage observed by fluorescein angiography. Optical coherence tomography is
      an accurate and reproducible method to measure retinal nerve fiber layer
      thickness. Particularly, when used in combination with other optic nerve imaging
      techniques, it can be used to differentiate glaucomatous eyes from normal eyes.
      Despite its usefulness, OCT has its limitations. Optical coherence tomography
      equipment is expensive, and not all insurance companies reimburse this procedure.
      Image quality is dependent on operator technique and can be degraded in the
      presence of media opacity. Change analysis software for glaucoma applications is
      not fully developed, and there is a scarcity of age, gender, and race-specific
      normative data upon which to compare eyes with retinal disease and glaucoma. In
      the next few years, it is likely that the role of OCT as a method to diagnose and
      manage retinal disease and glaucoma will be further defined, and many of the
      current limitations will be overcome. CONCLUSIONS: Optical coherence tomography
      is a useful imaging technique to diagnose and manage a variety of retinal
      diseases and glaucoma. Care is needed to avoid artifacts and image
      misinterpretation.

PMID- 14700660
TI  - Contact lens-related corneal ulcers in compliant patients.
AB  - PURPOSE: To report a case series of contact lens-related corneal ulcers in
      compliant patients with no apparent predisposing factors. DESIGN: Retrospective
      case series. METHODS: Charts of 70 patients with contact lens-related corneal
      ulcers from July 1999 to June 2002 were reviewed. Lens care hygiene and method of
      disinfection, as well as frequency of lens replacement, were recorded. Only
      patients who followed recommended guidelines for contact lens wear were included
      in the study. RESULTS: Of the 70 patients, 21 (30%) developed corneal ulcers
      despite being compliant with the guidelines for contact lens wear. All patients
      used multipurpose solutions for cleaning, disinfecting, and storing daily wear
      soft contact lenses. CONCLUSION: Standard lens care hygiene does not seem to be
      sufficient in preventing the development of corneal ulcers in patients using
      conventional and frequent replacement daily wear soft contact lenses.

PMID- 14700661
TI  - Triamcinolone acetonide-assisted peeling of the internal limiting membrane.
AB  - PURPOSE: We report on a new technique to peel the internal limiting membrane
      (ILM) using triamcinolone acetonide (TA) to facilitate visualization during
      surgery. DESIGN: Interventional case series. METHODS: In four eyes of four
      patients with macular hole, TA was used during vitrectomy to visualize the
      hyaloid. After the posterior hyaloid was surgically separated from the optic
      nerve head and posterior retina, TA suspension was injected over the posterior
      pole. Intraocular forceps was used to peel the ILM in a circumferential manner
      around the macular hole. RESULTS: Numerous particles of TA were dispersed over
      the posterior retina as white specks. Once the ILM was peeled, the peeled area
      was clearly visualized as an area lacking the white specks. In all patients, the
      macular holes closed. No adverse reactions were observed during the 3-month
      follow-up period. CONCLUSIONS: TA-assisted ILM peeling is an effective and safe
      technique for macular hole surgery.

PMID- 14700662
TI  - Resuturing the scleral flap through conjunctiva for treatment of excess
      filtration.
AB  - PURPOSE: To elevate the intraocular pressure (IOP) in eyes with persistent
      hypotony caused by excess filtration after trabeculectomy. DESIGN: Interventional
      case series. METHODS: The scleral flap was sutured directly through the
      conjunctival flap using a round, tapered needle with a 10-0 nylon suture. This
      procedure has been performed in 10 eyes. RESULTS: The IOP elevated from 2.6 (+/-
      1.0) mm Hg to 8.8 (+/- 3.7) mm Hg in 1 week and has been maintained between 6 to
      14 mm Hg during the follow-up. Hypotony maculopathy has disappeared in nine eyes.
      The suture was buried in the conjunctiva spontaneously in 1 week in all cases. No
      complications developed. CONCLUSIONS: Suturing the scleral flap directly through
      the conjunctival flap is a simple and effective modality to treat the hypotony
      caused by excess filtration after trabeculectomy.

PMID- 14700663
TI  - Iatrogenic open globe eye injury following sinus surgery.
AB  - PURPOSE: To report a case of iatrogenic open globe eye injury occurring during
      endoscopic sinus surgery. DESIGN: Case report and literature review. METHODS: A
      10-year-old boy presented with periorbital swelling and subconjunctival
      hemorrhage of the left eye following bilateral nasal adenoidectomy. Funduscopic
      examination showed evidence of a full-thickness open globe injury at the equator
      in the inferior nasal midperiphery. RESULTS: The injury most likely was secondary
      to inadvertent perforation of the lamina papiracea with entrance into the orbit
      and subsequent penetration of the globe. CONCLUSION: Sinus surgery has been
      reported previously in association with severe orbital complications. We are
      unaware of previous reports of open globe injury following sinus surgery.

PMID- 14700664
TI  - Orbital cellulitis, panophthalmitis, and ecthyma gangrenosum in an
      immunocompromised host with pseudomonas septicemia.
AB  - PURPOSE: To describe a case of Pseudomonas aeruginosa septicemia complicated by
      orbital cellulitis, panophthalmitis, and ecthyma gangrenosum. DESIGN:
      Observational case report. METHODS: An immunosuppressed 62-year-old man developed
      an unusual skin rash and a painful, swollen right eye with decreased vision. He
      had myelodysplastic syndrome and P. aeruginosa septicemia. The skin rash
      manifested as ecthyma gangrenosum. Metastatic orbital cellulitis and
      panophthalmitis was diagnosed. RESULTS: Despite intravitreal and topical
      gentamicin, the patient eventually required enucleation. CONCLUSIONS: This case
      represents a rare combination of events: an immunocompromised man developed
      pneumonia, P. aeruginosa septicemia, and endogenous seeding of the Pseudomonas to
      the skin, orbit, and eye. Early recognition of endogenous ophthalmic disease is
      imperative. The prognosis of combined orbital cellulitis and panophthalmitis is
      poor.

PMID- 14700665
TI  - Positioning the obese or large-breasted patient for macular laser
      photocoagulation.
AB  - PURPOSE: To report a positioning method for macular laser photocoagulation in
      obese or large-breasted patients. DESIGN: Report of a laser technique. METHODS:
      Review of clinical experience. SETTING: Private retina practice. RESULTS:
      Standing the patient up, leaning forward, and using the examination chair as
      buttocks support allows easier positioning of the obese or large-breasted patient
      in the slit lamp. The laser surgeon's hand manipulating the slit-lamp joystick
      does not fatigue, which allows more careful examination and treatment in these
      delicate cases. CONCLUSIONS: The technique described may allow more thorough
      diagnostic evaluation and focal laser treatment of obese and large-breasted
      patients with macular diseases.

PMID- 14700666
TI  - Optical coherence tomography findings in familial foveal retinoschisis.
AB  - PURPOSE: To report the optical coherence tomography findings of a 5-year-old boy
      with familial foveal retinoschisis. DESIGN: Observational case report. METHODS:
      Optical coherence tomography findings in familial foveal retinoschisis was
      evaluated. RESULTS: Optical coherence tomography findings demonstrated a wide
      hyporeflective space that split the neurosensory retina into a thin faintly
      reflective outer layer and a thicker more reflective inner retinal layer.
      Anteroposterior or oblique linear columns were seen across this hyporeflective
      space and formed a bridge between the outer and inner retinal layers. Cleavage
      planes were outer plexiform layer and adjacent nuclear layers. CONCLUSION:
      Optical coherence tomography findings in familial foveal retinoschisis in early
      childhood may help us to understand the early stages of pathology.

PMID- 14700667
TI  - Two patients with severe corneal disease in KID syndrome.
AB  - PURPOSE: To report two independent Japanese patients with keratitis, ichthyosis,
      and deafness (KID) syndrome and severe corneal disorder. DESIGN: Observational
      case reports. METHODS: Clinical observation of a 5-year-old boy (Patient 1) and a
      64-year-old man (Patient 2) with KID syndrome, presenting prominent corneal
      diseases. Molecular genetic assessment of the GJB2 gene encoding connexin-26 was
      performed. RESULTS: Patient 1 had bilateral diffuse superficial punctuate
      keratopathy with severe corneal neovascularization. He had a missense mutation of
      the GJB2 gene. Patient 2 had bilateral corneal stromal keratitis and right
      corneal ulceration with rupture of the Descemet membrane. He did not have any
      pathologic mutation of the GJB2 gene. The area of palisades of Vogt was
      diminished and tear production reduced in both patients. Topical eye drops, and
      corticosteroid or antibiotics, respectively, relieved them effectively.
      CONCLUSION: The impaired ocular surface regulating system might be a cause of
      corneal disease in KID syndrome and it can be treated by eye drops.

PMID- 14700668
TI  - In vivo observation of internal limiting membrane in an eye with macular hole.
AB  - PURPOSE: To determine whether an internal limiting membrane (ILM) in the foveal
      area with a full-thickness idiopathic macular hole (MH) was intact. DESIGN:
      Interventional case report. METHODS: The ILM was stained with indocyanine green
      and peeled with forceps during pars plana vitrectomy for a full-thickness MH with
      a cuff. The stained membrane over the MH was carefully examined to determine
      whether a hole was present. RESULTS: The ILM was clearly observed by indocyanine
      green staining during pars plana vitrectomy; no hole was detected in the membrane
      over the MH. CONCLUSIONS: A full-thickness MH with a cuff can occur in the
      absence of a hole in the ILM.

PMID- 14700669
TI  - Descemet membrane detachment with hemorrhage after alkali burn to the cornea.
AB  - PURPOSE: To report two cases of Descemet membrane detachment associated with
      hemorrhage after alkali burn to the cornea. DESIGN: Observational case reports.
      METHODS: We describe two patients with detachment of Descemet membrane associated
      with hemorrhage after alkali burns to the cornea. RESULTS: Patient 1 received a
      splash of caustic soda to the face. Descemet membrane detachment with hemorrhage
      was present. An attempt at reattachment using intraocular gases failed. Patient 2
      sustained a chemical burn secondary to an airbag injury. A thickened, detached
      Descemet membrane associated with a hyphema was evident. CONCLUSIONS: Detachments
      of Descemet membrane associated with alkali burns are often accompanied by
      irreversible endothelial cell damage.

PMID- 14700670
TI  - Bartonella henselae infection associated with neuroretinitis, central retinal
      artery and vein occlusion, neovascular glaucoma, and severe vision loss.
AB  - PURPOSE: To report a case of Bartonella henselae infection. DESIGN: Observational
      case report. METHODS: Review of the clinical, laboratory, photographic, and
      angiographic records of a patient with cat scratch disease associated with
      central retinal artery and vein occlusion, neovascular glaucoma, and severe
      vision loss. RESULTS: A 21-year-old man had no light perception in the left eye
      secondary to concurrent central retinal artery and vein occlusion believed to
      have resulted from infection with Bartonella henselae. Forty days later, he
      developed neovascular glaucoma in the left eye. CONCLUSION: Ocular complications
      associated with Bartonella henselae infection may include central retinal artery
      and vein occlusion, neovascular glaucoma, and severe vision loss.

PMID- 14700671
TI  - Detection of localized retinal dysfunction in a choroideremia carrier.
AB  - PURPOSE: To investigate severe unilateral vision loss in a choroideremia carrier.
      DESIGN: Case report. METHODS: Ocular examination, genetic testing, Humphrey
      visual fields, full-field and multifocal (mf) electroretinogram (ERG) tests were
      used to study a family with choroideremia. RESULTS: In a carrier with unilateral
      central vision loss, mfERG showed severely reduced amplitudes which correlated
      with a band of retinal pigment epithelial and choroidal atrophy in the macula, a
      dense central scotoma on Humphrey visual fields testing, and decreased ERG
      amplitudes. CONCLUSIONS: Multifocal ERG may be a sensitive tool to measure
      functional abnormalities in choroideremia carriers. Mosaic inactivation of the
      normal gene may cause expression of the mutation with severe vision loss in
      choroideremia carriers.

PMID- 14700672
TI  - Pressure alopecia following vitreoretinal surgery.
AB  - PURPOSE: To describe a patient with pressure alopecia following vitreoretinal
      surgery. DESIGN: Case report. METHODS: An 11-year-old boy underwent vitreoretinal
      surgery for left retinal detachment. One week postoperatively, his parents
      noticed a patch of alopecia where his head may have been in contact with the
      wrist-rest assembly placed around the head during the surgical procedure.
      RESULTS: Pressure alopecia on the parieto-occipital region of the scalp was
      observed. Hair regrowth occurred during the follow-up visits. CONCLUSION:
      Pressure alopecia is a rare complication of lengthy surgery and is
      underrecognized in ophthalmic practice. Precautions should be taken to avoid this
      preventable complication.

PMID- 14700673
TI  - Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma.
AB  - DESIGN: Interventional case report. METHODS: In an institutional practice
      setting, two women, aged 25 and 45, developed acute myopia after starting
      topiramate for epilepsy. One patient also developed bilateral angle closure
      glaucoma. RESULTS: Topiramate was discontinued. Anterior chamber shallowing was
      noted in both patients at presentation. Ultrasonography showed ciliochoroidal
      effusion. Baseline measurements of anterior chamber depth and lens thickness were
      obtained. CONCLUSIONS: Topiramate may be associated with ciliochoroidal effusion
      with forward displacement of the lens-iris diaphragm and anterior chamber
      shallowing, resulting in acute myopia and angle-closure glaucoma. Increased lens
      thickness contributes only minimally (9%-16%) to anterior chamber shallowing.

PMID- 14700674
TI  - Intracorneal hematoma with descemet membrane detachment after viscocanalostomy.
AB  - PURPOSE: To describe a case of intracorneal hematoma with Descemet membrane
      detachment after viscocanalostomy. DESIGN: Interventional case report. METHODS: A
      63-year-old with uncontrolled primary open-angle glaucoma underwent
      viscocanalostomy. During the introduction of hyaluronate 2.3% under the
      superficial flap, a limited lysis of Descemet membrane was observed. RESULT: Slit
      lamp biomicroscopy showed an intracorneal hematoma with Descemet membrane
      detachment 1 day after viscocanalostomy. The creation of an intentional break of
      Descemet membrane and descemetopexy using sulfur hexafluoride gas were performed.
      The cornea regained transparency after surgery. CONCLUSIONS: Intracorneal
      hematoma with Descemet membrane detachment is a possible complication of
      viscocanalostomy.

PMID- 14700675
TI  - Neodymium:yttrium-aluminum-garnet laser arteriotomy with embolectomy for central
      retinal artery occlusion.
AB  - PURPOSE: To describe a patient with central retinal artery occlusion successfully
      treated with neodymium:yttrium-aluminum-garnet laser arteriotomy and embolectomy.
      DESIGN: Interventional case report. METHODS: A 77-year-old woman noted sudden
      loss of vision after vigorous coughing. A central retinal artery occlusion was
      diagnosed. Four hours after symptoms appeared, arteriotomy and embolectomy with
      neodymium:yttrium-aluminum-garnet laser was performed. RESULTS: Displacement of
      embolus outside the artery with return of retinal perfusion and recovery of
      vision. Laser treatment also resulted in vitreous hemorrhage and false aneurysm
      formation of the central retinal artery. CONCLUSIONS: Neodymium:yttrium-aluminum
      garnet laser arteriotomy in a patient with central retinal artery occlusion
      resulted in extrusion of the embolus, reopening of the central retinal artery,
      and return of vision. This technique warrants further study as a primary
      treatment for this blinding disorder.

PMID- 14700676
TI  - Intraocular pressure profile of a child on a systemic corticosteroid.
AB  - PURPOSE: To report the ocular hypertensive response to high-dose systemic
      corticosteroid in a pediatric patient. DESIGN: Observational case report.
      METHODS: A 9-year-old patient with leukemia received oral prednisolone at a
      dosage of 2.3 mg/kg/d for 5 weeks, followed by a 4-month break and then a 4-week
      course of oral dexamethasone at 10 mg/d. Detailed ocular examination was
      performed for both eyes before and regularly throughout the two courses of
      treatment. RESULTS: The intraocular pressure in both eyes rose to almost 40 mm Hg
      after only 8 days of oral corticosteroid. On stopping systemic corticosteroid,
      the intraocular pressure rapidly returned to baseline level within 2 days. A
      similar intraocular pressure profile was recorded for both eyes during the course
      of oral dexamethasone. The patient remained largely asymptomatic throughout.
      CONCLUSIONS: Systemic corticosteroid may give rise to significant but
      asymptomatic ocular hypertension in pediatric patients.

PMID- 14700677
TI  - Retinal detachment from inadvertent intraocular injection of botulinum toxin A.
AB  - PURPOSE: To report a case of inadvertent intraocular injection of botulinum toxin
      A (Botox, BTA) resulting in a retinal tear and bullous retinal detachment. The
      retinal detachment resolved spontaneously, and the tear was treated with laser
      demarcation with good visual outcome. DESIGN: Interventional case report.
      METHODS: A 36-year-old woman underwent Botox injections for paralytic esotropia
      and developed ocular perforation. Dilated fundus examination showed a slit-like
      retinal tear infranasally with a bullous retinal detachment nasally. RESULTS: The
      retinal detachment spontaneously resolved, and the patient was treated with laser
      demarcation on the following day. After 2 more days, her vision returned to
      baseline. CONCLUSIONS: Botox did not appear toxic to human intraocular tissues.
      Close observation may be indicated in the event of an inadvertent intraocular
      Botox injection.

PMID- 14700678
TI  - Endogenous endophthalmitis after otitis media.
AB  - PURPOSE: To report a case of bacterial endophthalmitis after otitis media in a
      healthy adult. DESIGN: Interventional case report. METHODS: A healthy 49-year-old
      Caucasian woman developed acute otitis media of the right ear. Three weeks after
      the first onset there was a recurrence of the otitis media, with perforation of
      the tympanic membrane. Two days after this, the woman presented at our clinic
      with endophthalmitis of the right eye. RESULTS: A culture of vitreous material
      grew Streptococcus pyogenes (Streptococcus Lancefield group A). The same strain
      was found in a smear from the perforated ear. Despite aggressive treatment, the
      affected eye had to be eviscerated. CONCLUSIONS: Otitis media can result in a
      bacteremia. This may, even in a healthy adult, lead to a devastating endogenous
      bacterial endophthalmitis.

PMID- 14700679
TI  - Severe visual loss caused by ocular perforation during chalazion removal.
AB  - PURPOSE: To report two cases of ocular perforation during chalazion removal
      procedures leading to severe vision loss. DESIGN: Observational case series.
      METHODS: Two patients presented with unilateral decreased vision after chalazion
      removal procedures. Complete ophthalmologic examinations were performed. RESULTS:
      Examination revealed a cherry red spot and perforation site in the first patient.
      In the second patient, there was an intraocular gas bubble and ischemic retina.
      CONCLUSIONS: Local anesthetic injections for procedures such as chalazia removal
      can result in ocular perforation. We postulate that the intraocular injections
      led to extremely high pressures, compromising the blood supply to the retina and
      optic nerve. Anesthetic injections for all procedures, even chalazia removal,
      should be done with great caution. It is imperative to avoid injection if ocular
      perforation is suspected, as the high pressure may cause the majority of the
      visual morbidity.

PMID- 14700680
TI  - Using the American Journal of Ophthalmology's website for assessing residency
      subcompetencies in practice-based learning.

PMID- 14700681
TI  - Trypan blue has a high affinity to cellular structures such as epiretinal
      membrane.

PMID- 14700683
TI  - Melanocytoma or congenital optic disk pigmentation?

PMID- 14700685
TI  - Comparison of latanoprost, bimatoprost, and travoprost in patients with elevated
      intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study.

PMID- 14700687
TI  - Vitreous surgery in pigmented rabbits using the new, noncontact wide-field
      viewing system.

PMID- 14700705
TI  - Physician and practice factors related to influenza vaccination among the
      elderly.
AB  - BACKGROUND: Influenza vaccination rates among adults, especially in minority
      populations, remain below national goals of 90%. This study investigated in
      diverse settings, facilitators of and barriers to patient influenza vaccination
      from the physician's perspective. METHODS: Two-stage, stratified, random-cluster
      sampling was employed to select 71 clinicians from inner-city, rural, suburban,
      and Veterans Affairs (VA) practices, and a random sample of 925 of their patients
      aged >/=65 years. Questionnaires and interviews based on the PRECEDE-PROCEED
      framework assessed clinician factors. Associations among clinician beliefs,
      practice characteristics, patient beliefs, and self-reported influenza
      vaccination status were determined. RESULTS: The clinician response rate was 85%
      (60/71). Several factors of the PRECEDE-PROCEED framework were associated with
      higher influenza vaccination rates. For instance, patients at practices with
      express vaccination clinics had higher vaccination rates than at clinics without
      such immunization programs (87% v 76%, p =0.01). Using multivariate models,
      influenza vaccination status was related to several patient factors, including
      plans to receive influenza vaccination next year (p <0.001); belief that those
      who are not vaccinated will contract influenza (p =0.049); and history of being
      screened for colon cancer (p =0.023). Influenza vaccination status was also
      related to several physician factors, including awareness of recommendation to
      vaccinate asthmatics (p =0.024); agreement with these recommendations (p =0.004);
      and practice type and setting ("strata"), of which the VA was highest.
      CONCLUSION: Through proactive office systems and education, physicians may
      influence patients' intentions to be vaccinated and thereby increase influenza
      vaccination rates.

PMID- 14700706
TI  - Parental vaccine safety concerns. The experiences of pediatricians and family
      physicians.
AB  - OBJECTIVES: Recently several concerns regarding vaccine safety have received
      significant media attention. Primary care physicians are the most common
      interface for parents with the immunization delivery system and are likely to
      have the greatest opportunity for exposure and experience with parental vaccine
      safety concerns. METHODS: Mail survey study of a national random sample of 750
      pediatricians (PDs) and 750 family physicians (FPs) was conducted in 2000.
      Outcome variables of primary interest included the number of parental vaccine
      refusals in the past year, frequency of specific parent vaccine safety concerns,
      and actions taken by physicians when parents refused a vaccine. Chi-square
      analysis was used to determine the significance of the association of each
      outcome variable of interest with physician specialty, frequency of vaccine
      refusal, and the demographic variables. Multivariate analysis explored the
      potential for independent predictors of physicians who experienced increases in
      vaccine refusal. RESULTS: The response rate was 70%. Overall, 93% of PDs and 60%
      of FPs reported at least one parental vaccine refusal in their practice in the
      past year. PDs also were more likely than FPs to report an increase in the number
      of vaccine refusals over the past year (18% v 8%, p =0.01), while FPs were more
      likely to report a decrease in vaccine refusals over the same time period (18% v
      11%; p <0.5). PDs were more likely than FPs to provide additional information
      regarding vaccines to parents who refused vaccines and/or to discuss the issue at
      later visits. The most common concerns of parents were related to short-term
      reactions and pain from multiple injections. CONCLUSIONS: While almost all PDs
      and most FPs experienced at least one vaccine refusal from parents in the past
      year, far fewer physicians of both specialties observed an increase in their
      occurrence. Physicians must work to be consistently well informed of both the
      benefits of immunization as well as the issues of parental concern regarding
      vaccine safety.

PMID- 14700707
TI  - Impact of vaccine shortages on immunization programs and providers.
AB  - BACKGROUND: During 2001 and the first half of 2002, the United States experienced
      severe shortages of five of the eight universally recommended vaccines for
      children. OBJECTIVES: To evaluate the impact of shortages of diphtheria-tetanus
      acellular pertussis vaccine (DTaP), pneumococcal conjugate vaccine (PCV7), and
      tetanus and diphtheria vaccine (Td) shortages on state and urban area
      immunization programs and immunization providers between September 2001 and
      January 2002. METHODS: (1) Survey of state and urban area immunization program
      managers. Outcome measures included changes in vaccine distribution and
      suspension of daycare/Head Start and school entry immunization requirements for
      Td, DTaP, and PCV7. (2) Interviews with Vaccines for Children Program
      immunization providers scheduled to receive a routine site visit between January
      21 and February 1, 2002. Outcome measures included problems experienced with
      vaccine orders, implementation of Advisory Committee on Immunization Practices
      (ACIP) interim recommendations for DTaP and PCV7, and length of time with no DTaP
      or PCV7 vaccines in stock. RESULTS: Over 85% of immunization programs changed the
      way they distributed PCV7, DTaP, and Td vaccines to providers, including limiting
      the amount of vaccine ordered or distributing partial orders. Additionally, 76%
      of programs experienced problems purchasing or receiving varicella vaccine. Sixty
      eight percent of programs suspended school entry requirements for Td.
      Immunization providers reported problems with orders of Td (56%), PCV7 (45%),
      DTaP (30%), and varicella (29%). Approximately 16% and 29% of providers
      implemented the interim ACIP recommendations for DTaP and PCV7, respectively.
      However, 21% of providers suspended administration of all doses of PCV7 because
      they ran out of vaccine before learning of the shortage. CONCLUSIONS: From
      suspension of school entry requirements to delaying administration of vaccine,
      the recent vaccine shortages affected immunization programs' and providers'
      ability to administer vaccines in a timely manner.

PMID- 14700708
TI  - Adolescent immunizations. are we ready for a new wave?
AB  - CONTEXT: Factors associated with vaccination coverage rates for the 20% of U.S.
      adolescents enrolled in managed care organizations (MCOs) are not known.
      OBJECTIVES: To examine recent trends in receipt of two doses of measles-mumps
      rubella (MMR2) and three doses of hepatitis B (Hep B3) among U.S. adolescents
      enrolled in managed care organizations (MCOs); to determine whether specific
      characteristics of MCOs are associated with higher vaccination rates; and to
      assess the impact of state middle school immunization requirements on these
      rates. DESIGN: Longitudinal (1996-1999) and cross-sectional (1999) analyses of
      National Committee for Quality Assurance (NCQA) data to estimate adolescent
      vaccination coverage rates for MMR2 and Hep B3. In 2002, using 1999 data only, a
      cross-sectional analysis examined the relationship of specific plan
      characteristics and state immunization laws with immunization coverage. MAIN
      OUTCOME MEASURES: Percentage of 13 year olds in MCOs with documented receipt of
      MMR2 and Hep B3. RESULTS: From 1996 to 1999, MMR2 rates increased from 56% to
      64%, and from 1997 to 1999, Hep B3 rates increased from 23% to 38%. By 1999,
      higher rates for both vaccines had been achieved in larger plans (p<0.001 and
      p<0.003 for MMR2 and Hep B3, respectively), those with the highest NCQA
      accreditation status (p<0.003), those in New England (p<0.001), and those in
      states with middle school immunization requirements (p<0.001). CONCLUSIONS:
      Despite encouraging increases, adolescent immunization rates are significantly
      below the Healthy People 2010 goal of 90%. State laws and accreditation
      incentives are effective. Research is needed to identify additional interventions
      to increase vaccination coverage in the adolescent population.

PMID- 14700709
TI  - Underimmunization in Chicago children who dropped out of WIC.
AB  - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) serves a large proportion of Chicago infants, but some discontinue
      participation before age 1 year. To determine if children who remained active at
      WIC immunization-linked sites after their first birthday were more likely to be
      immunized by ages 19 and 25 months than those who dropped out, a retrospective
      cohort study was conducted. METHODS: Four Chicago WIC sites that used monthly
      voucher pick-up were chosen. Children born from July 1, 1997 to September 30,
      1997 who attended these sites were eligible (N=1142). The cohort was divided into
      two groups: (1) active group (46%), who had a WIC visit on or after their first
      birthday; and (2) inactive group (54%), who had their last WIC visit before their
      first birthday. Children were enrolled through home visits. RESULTS: The records
      for 200 children were analyzed. By age 19 months, 65 (84%) of 77 active children
      had received one dose of measles-mumps-rubella vaccine (MMR), compared to 82
      (67%) of 123 inactive children (risk ratio [RR]=1.3; 95% confidence interval
      [CI], 1.1- 1.5). By age 25 months, 64 (83%) active children had received four
      doses of diphtheria-tetanus-pertussis vaccine (DTP), one MMR, and three doses of
      Haemophilus influenzae type b vaccine (Hib), compared with 64 (52%) inactive
      children (RR=1.6; 95% CI, 1.3-2.0). CONCLUSIONS: In this cohort, children active
      in WIC after their first birthday were more likely to be immunized by ages 19 and
      25 months, compared with those who were no longer active. Chicago children who
      drop out of WIC may represent those at highest risk for underimmunization and may
      require special strategies to improve coverage.

PMID- 14700710
TI  - Evaluation of invalid vaccine doses.
AB  - BACKGROUND: The 2002 Recommended Childhood Immunization Schedule clarified the
      definition of an invalid dose of vaccine as any dose administered >/=5 days
      before the minimum age or interval had elapsed. Any invalid dose of vaccine
      should be repeated. OBJECTIVE: Determine the proportion of U.S. children who
      received an invalid dose of vaccine, evaluate the impact on vaccination coverage
      levels if invalid doses were not counted, and determine the vaccine purchase cost
      if at least one invalid dose is repeated. METHODS: Provider-reported vaccination
      histories of children aged 19 to 35 months sampled by the 2000 National
      Immunization Survey were evaluated. Analyses were performed in 2002 after the
      2002 Advisory Committee on Immunization Practices (ACIP) Recommended Immunization
      Schedule was released. Any vaccine dose administered >/=5 days before the
      recommended minimum age or interval was classified as invalid. Change in
      vaccination coverage was determined by subtracting estimated valid-dose coverage
      (based on number of valid doses received) from the estimated up-to-date coverage
      (based on number of doses received regardless of age or spacing). RESULTS:
      Overall, 10.5% (+/-0.6%) of children had received at least one invalid dose of
      vaccine. Of the invalid doses, 51% were hepatitis B, 100% of which were the third
      dose; 19% were diphtheria-tetanus-pertussis (DTP/DTaP), 92% of which were the
      fourth dose; 12% were measles-containing vaccine (MCV); 15% were varicella
      vaccine; and 4% were polio vaccine, 96% of which were the first dose. Excluding
      invalid doses resulted in a small change in vaccination coverage: 2.2% for
      DTP/DTaP, 0.7% for polio, 6.5% for hepatitis B, 1.4% for MCV, and 1.7% for
      varicella. The vaccine purchase cost to repeat at least one invalid dose ranged
      from approximately $10 million (public-purchased) to approximately $18 million
      (private-purchased). CONCLUSIONS: Nationally about 595,000 of children aged 19 to
      35 months, born between February 1997 and May 1999, received at least one invalid
      dose of vaccine. The cost of revaccinating these children is substantial and may
      have a negative impact on parents, physicians, and vaccine purchasers. Educating
      immunization providers regarding proper immunization timing should be conducted
      to reduce the administration of invalid doses of vaccines.

PMID- 14700711
TI  - The price of prevention. cost of recommended activities to improve immunizations.
AB  - PURPOSE: To calculate the cost structure of a suite of immunization improvement
      interventions recommended by the Centers for Disease Control and Prevention
      (CDC). METHODS: A determination was made of the cost to clinics and agencies that
      implement a suite of CDC-recommended practice improvement interventions to fully
      immunize a child for diphtheria-tetanus-attenuated pertussis (DTaP), inactivated
      poliovirus (IPV), and measles-mumps-rubella (MMR) vaccines. Patient data were
      collected through chart analysis of 16-month-old children in clinics
      participating in this study's interventions between May 1997 and August 2000. The
      study began on October 1, 1996, and was funded for 5 years (until September 30,
      2002). RESULTS: Study calculations suggest that an additional $0.013/per patient
      per month would be needed to cover these activities. CONCLUSIONS: Identifiable
      cost structures are associated with the practice improvement strategies
      recommended by the CDC. The method of implementation may be as important as the
      interventions themselves. Present compensation for immunization may not actually
      cover the cost of service provision, and it is unlikely to cover the costs of
      practice improvement, as described in this paper.

PMID- 14700712
TI  - Adherence of mass vaccinators to timing guidelines for influenza vaccination.
AB  - BACKGROUND: With recent delays in influenza vaccine availability, practitioners
      have been encouraged to time vaccination activities to promote vaccination of
      high-priority groups first. This cross-sectional survey of persons vaccinated in
      nontraditional settings (NTS) by mass vaccinators was conducted to assess how
      effectively the mass vaccinators were able to implement these vaccination-timing
      guidelines. METHODS: In Minnesota, the Minnesota Visiting Nurse Agency (MVNA) is
      a major mass vaccinator in NTS. For the 2001-2002 vaccination season, MVNA
      developed several strategies designed to facilitate adherence to vaccination
      timing guidelines adopted by the Minnesota Department of Health. All persons
      vaccinated in the MVNA NTS clinics from October 2001 through December 2001 were
      surveyed in order to evaluate whether they were in a high-priority group and
      whether the timing of their vaccinations coincided with the timing promoted in
      the guidelines. RESULTS: A total of 46,174 of the 145,947 people vaccinated by
      the MVNA were vaccinated between October 14 and October 28, 2001, the time period
      designated for vaccination of high-priority groups. Of these, 41,143 (89%)
      responded to the priority group question and 27,211 (66%) indicated that they
      were in one of the targeted groups, including more than 19,000 Medicare
      recipients. At sites targeting senior citizens, more than 92% of initial vaccine
      recipients were in a targeted group. Overall, 48.4% of persons vaccinated at any
      time during the vaccination season were in a high-priority group. CONCLUSIONS:
      Mass vaccinators can successfully implement influenza vaccination timing
      guidelines in NTS.

PMID- 14700713
TI  - Community trends in the early detection of breast cancer in Wisconsin, 1980-1998.
AB  - BACKGROUND: Early detection of breast cancer is an important public health goal.
      Rates of early detection have increased over the past several decades,
      contributing to recent declines in mortality. Despite these overall trends,
      however, some populations have experienced less progress than others. METHODS:
      The rates of early detection, measured as the percentage of breast cancers
      diagnosed as breast carcinoma in situ, were calculated using data from
      Wisconsin's population-based tumor registry from 1980 to 1998. Trends in breast
      cancer (percent diagnosed in situ) were examined over time by socioeconomic
      characteristics of ZIP code of residence, using census data. RESULTS: The
      percentage of breast cancer cases that were breast carcinoma in situ was more
      than five times greater in the later period (1994-1998) (13.9%), compared with
      the early period (1980-1984) (2.6%). In the middle period (1987-1991), breast
      cancer was diagnosed as breast carcinoma in situ about one-third less frequently
      among women in areas with the lowest urbanization, median family income, and
      percent educated beyond high school, compared with communities with the highest
      levels of these variables. Recently disparities in early detection rates by
      community income and education indicators declined slightly, whereas disparities
      in percent of breast carcinoma in situ by urbanization did not. CONCLUSIONS:
      Communities with lower levels of income, education, and urbanization lagged in
      the early detection of breast cancer during the 1980s and, despite some progress
      during the 1990s, continue to be underserved. Women in these communities should
      be targeted for interventions to improve the early detection of breast cancer.

PMID- 14700714
TI  - Shared decision making about screening and chemoprevention. a suggested approach
      from the U.S. Preventive Services Task Force.
AB  - Shared decision making is a process in which patients are involved as active
      partners with the clinician in clarifying acceptable medical options and in
      choosing a preferred course of clinical care. Shared decision making offers a way
      of individualizing recommendations, according to patients' special needs and
      preferences, when some patients may benefit from an intervention but others may
      not. This paper clarifies how the U.S. Preventive Services Task Force (USPSTF)
      envisions the application of shared decision making in the execution of screening
      and chemoprevention. Unlike conventional USPSTF reports, this paper is neither a
      systematic review nor a formal recommendation. Instead, it is a concept paper
      that includes a commentary on the current thinking and evidence regarding shared
      decision making. Although the USPSTF does not endorse a specific style of
      decision making, it does encourage informed and joint decisions. This means that
      patients should be informed about preventive services before they are performed,
      and that the patient-clinician partnership is central to decision making. The
      USPSTF suggests that clinicians inform patients about preventive services for
      which there is clear evidence of net benefit, and, if time permits, about other
      services with high visibility or special individual importance. Clinicians should
      make sure that balanced, evidence-based information about the service (including
      the potential benefits and harms, alternatives, and uncertainties) is available
      to the patient if needed. For preventive services for which the balance of
      potential benefits and harms is a close call, or for which the evidence is
      insufficient to guide a decision for or against screening, clinicians should
      additionally assist patients in determining whether individual characteristics
      and personal preferences favor performing or not performing the preventive
      service. The USPSTF believes that clinicians generally have no obligation to
      initiate discussion about services that have either no benefit or net harm.
      Nonetheless, clinicians should be prepared to explain why these services are
      discouraged and should consider a proactive discussion for services with high
      visibility or special individual importance or for services for which new
      evidence has prompted withdrawal of previous recommendations.

PMID- 14700715
TI  - Promoting informed decisions about cancer screening in communities and healthcare
      systems.
AB  - Individuals are increasingly involved in decisions about their health care.
      Shared decision making (SDM), an intervention in the clinical setting in which
      patients and providers collaborate in decision making, is an important approach
      for informing patients and involving them in their health care. However, SDM
      cannot bear the entire burden for informing and involving individuals. Population
      oriented interventions to promote informed decision making (IDM) should also be
      explored. This review provides a conceptual background for population-oriented
      interventions to promote informed decisions (IDM interventions), followed by a
      systematic review of studies of IDM interventions to promote cancer screening.
      This review specifically asked whether IDM interventions (1) promote
      understanding of cancer screening, (2) facilitate participation in decision
      making about cancer screening at a level that is comfortable for individuals; or
      (3) encourage individuals to make cancer-screening decisions that are consistent
      with their preferences and values.Fifteen intervention arms met the intervention
      definition. They used small media, counseling, small-group education, provider
      oriented strategies, or combinations of these to promote IDM. The interventions
      were generally consistent in improving individuals' knowledge about the disease,
      accuracy of risk perceptions, or knowledge and beliefs about the pros and cons of
      screening and treatment options. However, few studies evaluated whether these
      interventions resulted in individuals participating in decision making at a
      desirable level, or whether they led to decisions that were consistent with
      individuals' values and preferences. More research is needed on how best to
      promote and facilitate individuals' participation in health care. Work is
      especially needed on how to facilitate participation at a level desired by
      individuals, how to promote decisions by patients that are consistent with their
      preferences and values, how to perform effective and cost-effective IDM
      interventions for healthcare systems and providers and in community settings
      (outside of clinical settings), and how to implement these interventions in
      diverse populations (such as populations that are older, nonwhite, or
      disadvantaged). Finally, work is needed on the presence and magnitude of barriers
      to and harms of IDM interventions and how they might be avoided.

PMID- 14700716
TI  - Shared medical decision making. A new tool for preventive medicine.

PMID- 14700717
TI  - Immunization, equity, and human rights.
AB  - There is much to be proud of with respect to progress in childhood immunization
      in the United States and around the world. However, the good fortune is not yet
      shared by all. There is more to be done in the United States, and much more to be
      done around the world to ensure that all children of the world enjoy the right to
      immunization.

PMID- 14700719
TI  - Concerns continue over mercury and autism.

PMID- 14700725
TI  - Posterior cingulate metabolic changes occur in Parkinson's disease patients
      without dementia.
AB  - The basis for cognitive deficits in Parkinson's disease (PD) is unknown.
      Hippocampal atrophy has been shown in Alzheimer's disease (AD) and PD. N-Acetyl
      aspartate (NAA)/creatine (Cr) ratio in the posterior cingulate gyrus (PCG) is
      decreased in AD, but unknown in PD. Volumetric magnetic resonance (MR) imaging
      (at 1.5 T) determined corrected HC volume and MR spectroscopy (MRS) PCG
      metabolites in 12 non-demented mild to moderately affected PD patients (six male,
      six female) and ten controls (five male, five female). Age (PD=60.6 years,
      control=62.2; P=0.62), education (PD=14.1 years, controls=13.8; P=0.89) and
      global cognition (Mini-Mental State Exam score: PD=28.7, controls=29.6; P=0.14)
      did not differ. Only recall (CVLT-II, P=0.046) and NAA/Cr (PD=1.53,
      controls=1.78; P=0.03) were decreased in PD. Memory correlated with NAA/Cr
      (r=0.65, P=0.02) in PD. In conclusion, cingulate metabolic changes occur in PD.

PMID- 14700726
TI  - Conduction failure of action potentials in sensory sural nerves of undernourished
      rats.
AB  - In order to determine possible functional and morphometrical alterations produced
      by perinatal undernourishment on peripheral nerves, sensory sural nerves from
      control and undernourished rats of 30 and 90 postnatal days of age were dissected
      and divided in two segments, one for recording the compound action potential
      (CAP) and the other for histological examination. Nerves from undernourished
      animals showed maximal CAP responses of smaller amplitude and area, larger trial
      to-trial variability in area, and a significant reduction in axonal myelin sheath
      thickness than nerves from control animals. It is suggested that perinatal
      undernourishment produces changes in axonal myelin sheath structure, resulting in
      severe alterations in the generation and propagation of action potentials (block
      and/or intermittent conduction) in sensory afferent fibers in the rat.

PMID- 14700727
TI  - Effects of phencyclidines on signal transfer from the entorhinal cortex to the
      hippocampus in rats.
AB  - The information transfer from the superficial layers of the entorhinal cortex
      (EC) to the hippocampus is regulated in a frequency dependent manner.
      Phencyclidine and related compounds such as MK-801 produce psychotic symptoms
      that closely resemble schizophrenia. We studied the effects of systemic
      administration of MK-801 on the signal transfer from the EC layer III to the
      hippocampal area CA1. High frequency (above 10 Hz) activation of the bi-synaptic
      entorhinal input in control animals results in a strong suppression of the field
      potentials in the stratum lacunosum-moleculare of the area CA1. In contrast, in
      MK-801 pretreated rats the field response was less reduced. The field potential
      responses evoked in these two groups of animals by high-frequency activation of
      the monosynaptic input were similar suggesting selective alterations in layer III
      of the medial EC. We suggest, that MK-801 causes disinhibition of layer III
      projection cells and, therefore, may cause strong, pathological activation of
      direct layer III-CA1 pathway.

PMID- 14700728
TI  - Neurotrophin receptors in taste buds of adult zebrafish (Danio rerio).
AB  - TrkB plays crucial roles in the development and maintenance of taste buds in
      mammals. In this study we investigated the presence and cell localization of Trks
      (TrkA, TrkB and TrkC) in taste buds of the zebrafish (Danio rerio) using Western
      blot and immunohistochemistry. Proteins of 140 and 145 kDa, identified as full
      length TrkA and TrkB, were detected. Conversely, the anti-TrkC antibody
      recognized a protein lower than expected (100 kDa). In agreement with these
      results the sensory cells of taste buds, displayed TrkA- and TrkB-like, but not
      TrkC-like, immunoreactivity. TrkA and TrkB co-existed in the same taste buds, but
      remains to be clarified whether or not they are co-expressed in the same cells.
      Present results demonstrate that as for mammals neurotrophins might play a role
      in sensory cells of the teleostean taste buds.

PMID- 14700729
TI  - The effect of musical training on the neural correlates of math processing: a
      functional magnetic resonance imaging study in humans.
AB  - The neural correlates of the previously hypothesized link between formal musical
      training and mathematics performance are investigated using functional magnetic
      resonance imaging (fMRI). FMRI was performed on fifteen normal adults, seven with
      musical training since early childhood, and eight without, while they mentally
      added and subtracted fractions. Musical training was associated with increased
      activation in the left fusiform gyrus and prefrontal cortex, and decreased
      activation in visual association areas and the left inferior parietal lobule
      during the mathematical task. We hypothesize that the correlation between musical
      training and math proficiency may be associated with improved working memory
      performance and an increased abstract representation of numerical quantities.

PMID- 14700730
TI  - 5-Aminoimidazole-4-carboxamide-ribonucleoside enhances oxidative stress-induced
      apoptosis through activation of nuclear factor-kappaB in mouse Neuro 2a
      neuroblastoma cells.
AB  - AMP-activated protein kinase (AMPK) was recently suggested to have a pro
      apoptotic effect although its primary function is believed to mediate cellular
      adaptation to metabolic stresses. Here, we investigated the effect of the AMPK
      activator 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) on oxidative
      stress-induced apoptosis using mouse Neuro 2a neuroblastoma cells. H2O2-induced
      apoptosis was increased by AMPK activation, either with AICAR pretreatment or
      with overexpression of active AMPK. AICAR also induced nuclear factor-kappaB (NF
      kappaB) activation along with activation of p38 mitogen-activated protein kinase
      and c-Jun N-terminal kinase. Correlation between NF-kappaB activation and the
      AICAR-enhanced apoptotic cell death was observed. In addition, NF-kappaB
      inhibitor SN50 prevented the augmented cell death by AICAR. Thus, our data
      suggest that NF-kappaB mediates the pro-apoptotic effect of AICAR.

PMID- 14700731
TI  - Expression of Musashi1, a neural RNA-binding protein, in the cochlea of young
      adult mice.
AB  - Musashi1 (Msi1) is an RNA-binding protein expressed in neural stem/progenitor
      cells, astroglial progenitor cells and astrocytes in the vertebrate central
      nervous system. We hypothesized that Msi1 is expressed in only some of the
      supporting cells in the cochlea, which could become hair cell progenitors under
      special circumstances after an injury. To observe this, we investigated Msi1
      expression in young adult mouse cochlea by immunohistochemistry using monoclonal
      antibody against Msi1. Msi1 immunostaining was found in a variety of supporting
      cells but not in outer hair cells in the organ of Corti. Although an
      immunoreactive ring was found around the inner hair cells, it also seemed to
      originate from the supporting cells. We suppose that this wide expression of Msi1
      in supporting cells indicates that those cells might have the potential to become
      hair cell progenitors if injured, but that some other mechanisms strictly inhibit
      this ability.

PMID- 14700732
TI  - Nucleus accumbens and medial prefrontal cortex dopaminergic response to self
      administered cocaine in naive rats.
AB  - Cocaine reinforcement is strongly associated with increased nucleus accumbens
      dopamine (NAcc DA). The involvement of medial prefrontal cortex (mPFC) DA in
      cocaine reward is less defined, but substantial evidence indicates that increased
      mPFC DA may suppress NAcc DA levels. Using in vivo microdialysis, NAcc or mPFC DA
      was determined in cocaine-naive rats after a self-administered cocaine injection
      (3.0 mg/kg). Extracellular levels of NAcc DA were dramatically enhanced 10 min
      post-cocaine injection, but dropped significantly at each subsequent assessment.
      mPFC DA also increased significantly, but to a lesser extent than observed in the
      NAcc. Findings of prominent DA increases in both the NAcc and mPFC terminals
      during the test session indicate that NAcc DA responses do not appear to be
      inhibited by increased mPFC DA during cocaine self-administration.

PMID- 14700733
TI  - Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin
      transporter-mediated dopamine uptake.
AB  - Although studies have suggested that dopamine can be transported by serotonin
      transporters (SERTs), such activity has not been characterized at the cloned
      SERTs. Dopamine and serotonin uptake by human SERT expressed in HEK-293 cells was
      compared at 37 and 40 degrees C. Elevated temperature was found to alter
      serotonin transport, but had no significant effect on dopamine transport. These
      effects led to a 10-fold increase in the serotonin:dopamine transport ratio
      reflecting an increased preference of SERTs for dopamine as opposed to serotonin
      at the higher temperature. The effects of 3,4-methylenedioxymethamphetamine
      (MDMA) on SERT-mediated dopamine transport were also evaluated by pre-incubating
      SERT-expressing cells with MDMA. The presence of intracellular MDMA caused a
      decrease in [3H]dopamine uptake but had no effect on [3H]serotonin transport
      suggesting that intracellular MDMA may be capable of inhibiting transporter
      function.

PMID- 14700734
TI  - p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic
      SH-SY5Y cells.
AB  - Decreased proteasome activity is an important pathology in Parkinson's disease
      (PD), which is related to cell death and Lewy body formation. In this study, we
      show that p53-activity may correlate with neuronal death via the mitochondrial
      pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of
      p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased
      stabilization of p53 upregulated the level of Bax and mitochondrial
      depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha
      (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132
      induced cell death. These results suggest that p53 is a candidate as an
      intermediary between the proteasome system and mitochondria-related neuronal
      death in PD.

PMID- 14700735
TI  - Consumption of high carbohydrate, high fat, and normal chow is equally suppressed
      by a cannabinoid receptor antagonist in non-deprived rats.
AB  - Administration of the CB1 receptor antagonist SR 141716 [N-piperidino-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] suppresses
      intake of highly palatable (high carbohydrate) food. However, the effects of SR
      141716 on intake of foods with varying macronutrient compositions, and in non
      deprived animals have not been well studied. In the present study, non-deprived
      rats were injected intraperitoneally with SR 141716 (0.03-3.0 mg/kg) and
      presented with a high carbohydrate, high fat, or normal chow diet. Food intake
      and locomotor activity were recorded for 120 min. Results showed that SR 141716
      significantly suppressed food intake irrespective of the composition of the test
      food without affecting locomotor activity. These data suggest that food
      deprivation or high palatability of the ingesta are not necessary to observe the
      suppressive effects of SR 141716 on food intake.

PMID- 14700737
TI  - Positive effects of deprenyl and estradiol on spatial memory and oxidant stress
      in aged female rat brains.
AB  - Increasing age decreases spatial learning and memory. Spatial learning is
      coordinated with different brain regions. Since the oxidative damage may play a
      role in the aging process, including the associated cognitive decline, age
      related impairment in spatial learning and memory may be alleviated by
      antioxidant treatment. The present study examined the effects of the monoamine
      oxidase B inhibitor L-deprenyl, alone and in combination with estradiol, on
      spatial memory using the Morris water maze and oxidant stress in aged female rat
      brains. We demonstrated that co-administration of deprenyl and estradiol caused a
      synergistic effect on spatial memory. However, use of either deprenyl or
      estradiol alone increased antioxidant enzyme activities in brain and reduced
      lipid peroxidation. Therefore, positive effects of deprenyl and estradiol on
      spatial memory may occur due not only to their antioxidant activities but also to
      the different actions.

PMID- 14700736
TI  - Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role
      of extracellular and intracellular calcium ions.
AB  - Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10,
      25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical
      characteristics of nuclear shrinkage, condensation, and DNA breakage as well as
      formation of apoptotic bodies observed by fluorescence staining, terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet
      assays. Such effects of alcohol on cerebral VSMCs were time- and concentration
      dependent. The threshold ethanol concentration for induction of the apoptotic
      process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators,
      i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM)
      and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6)
      M), respectively, ameliorated greatly the number of cerebral VSMCs which
      underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral
      VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may
      contribute to alcohol-induced brain-vascular damage and stroke. In addition, our
      findings point to potential caution for humans who imbibe two or more standard
      drinks per day or who undergo 'binge drinking'.

PMID- 14700738
TI  - Stroke-prone rats exhibit prolonged behavioral deficits without increased brain
      injury: an indication of disrupted post-stroke brain recovery of function.
AB  - Stroke-prone rat strains exhibit an increased stroke risk and sensitivity, and
      reduced endogenous mechanisms of ischemic brain tolerance. This experiment
      provides a comparative, serial evaluation of neurological deficits and brain
      injury following middle cerebral artery occlusion/permanent focal stroke in this
      high-risk strain. Stroke-prone spontaneously hypertensive (SHR-SP), spontaneously
      hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated over 28 days using
      magnetic resonance imaging (MRI), histopathology, and neurobehavioral testing. T2
      and diffusion weighted-MRI was performed after 1, 10 and 28 days to measure the
      degree of stroke-induced brain injury. Normotensive WKY rats receiving the same
      stroke and other SHR-SP rats receiving sham surgery were used for control
      comparisons. Functional deficits were scored after 1, 4, 11, 18 and 28 days. The
      degree of brain infarction/injury was practically identical in hypertensive and
      stroke-prone rats. WKY rats exhibited significantly smaller infarcts (P<0.05),
      with neurological function recovering quickly to normal by day 11 in this strain.
      Functional deficits persisted longer in hypertensive rats, with function
      recovering to normal by day 18 (P<0.05). Functional deficits in SHR-SP rats
      persisted the longest, and were observed even after 28 days (P<0.05). This
      increased and prolonged neurologic dysfunction exhibited by SHR-SP compared to
      SHR rats, while exhibiting practically identical degrees of brain
      injury/infarction, reflects the increased stroke risk and sensitivity of this
      strain and suggests a reduced SHR-SP brain plasticity following injury.
      Therefore, the stroke-prone rat provides an enhanced and prolonged functional
      deficit model that can be used to elucidate those mechanisms/novel targets
      critical to longitudinal neurobehavioral recovery post-stroke.

PMID- 14700739
TI  - Chronic intoxication with 3-nitropropionic acid in rats induces the loss of
      striatal dopamine terminals without affecting nigral cell viability.
AB  - 3-Nitropropionic acid (3NP) is a succinate dehydrogenase inhibitor allowing the
      generation of animal models of Huntington's disease. In the present study, we
      found that a 5-day continuous chronic infusion of 3NP produces loss of
      [3H]mazindol binding and tyrosine hydroxylase (TH) immunoreactivity in the
      striatal area of degeneration. This loss of dopamine terminals was not due to a
      loss of nigral neurons since the expression of TH as well as the number of TH
      expressing neurons remained unaltered in the substantia nigra of rats treated by
      3NP. This suggests that the 3NP-induced dopamine terminal loss is secondarily
      related to the striatal degeneration andlor to a direct effect of 3NP on striatal
      terminals and not to a primary effect on nigral cells.

PMID- 14700740
TI  - Effects of gender and gonadal hormones on nociceptive responses to intraplantar
      carrageenan in the rat.
AB  - The effects of gender and gonadal hormones on nociceptive responses to
      intraplantar carrageenan in the rat were investigated. A plantar analgesic meter
      was used to measure carrageenan-induced changes in paw withdrawal latency (PWL)
      values, and von Frey monofilaments were used to assess changes in paw withdrawal
      threshold (PWT) values in response to tactile-evoked (mechanical) stimuli. The
      data revealed that PWL values were significantly greater in gonadally-intact
      females than in gonadally-intact males, and this response was abolished by
      surgical gonadectomies. Gonadally-intact as well as gonadectomized male and
      female rats also exhibited significant carrageenan-induced decreases in PWT, but
      neither sex- nor gonadectomy-related differences were detected in the development
      of mechanical allodynia. These findings demonstrate that intraplantar carrageenan
      induces nociceptive behaviors in rats that are differentially affected by sex and
      gonadal hormones.

PMID- 14700741
TI  - Cortistatin, a modulatory peptide of sleep and memory, induces analgesia in rats.
AB  - Cortistatin is a neuropeptide structurally related to somatostatin that induces
      sleep and interferes with the memory process. Very likely affecting other
      neurotransmission systems, such as: acetylcholine, gamma-aminobutyric acid, and
      noradrenaline. For example, cortistatin inhibits acetylcholine excitatory actions
      in the hippocampus. It is known that acetylcholine is involved in the regulation
      of several processes, such as pain, temperature, sleep, and memory. Since
      cortistatin seems to interact with acetylcholine, we decided to explore whether
      cortistatin participates in the system that modulates the noxious stimulus-evoked
      behavior. The intracerebroventricular administration of cortistatin increased the
      threshold to evoke a defensive behavior by a nociceptive stimulus. These
      observations suggest that cortistatin is part of the system that regulates pain
      perception.

PMID- 14700742
TI  - Temporal lobe pathology of human patients with neurofilament inclusion disease.
AB  - Neurofilament inclusion disease (NID) is a novel neurodegenerative disease
      characterized histologically by the presence of neurofilament positive neuronal
      inclusions (NI) and swollen achromatic neurons (SN). The density and distribution
      of NI and SN were studied in areas of the temporal lobe in four cases of NID. In
      NID, the density of the NI and SN was greater in areas of the cerebral cortex
      compared with the hippocampus and dentate gyrus. Lesion densities were similar in
      the different gyri of the temporal cortex and in the various cornu ammonis
      sectors of the hippocampus. In the cerebral cortex, the density of the NI and SN
      was greater in the lower compared with the upper cortical laminae. There was no
      significant correlation between the densities of the NI and SN. The distribution
      of the temporal lobe pathology of NID has several differences from that reported
      in Pick's disease and corticobasal degeneration supporting the hypothesis that
      NID is a novel and unique type of neurodegenerative disease.

PMID- 14700743
TI  - Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for
      improved glycemic control of type 2 diabetes.
AB  - Exenatide (synthetic exendin-4), glucagon-like peptide-1 (GLP-1), and GLP-1
      analogues have actions with the potential to significantly improve glycemic
      control in patients with diabetes. Evidence suggests that these agents use a
      combination of mechanisms which may include glucose-dependent stimulation of
      insulin secretion, suppression of glucagon secretion, enhancement of beta-cell
      mass, slowing of gastric emptying, inhibition of food intake, and modulation of
      glucose trafficking in peripheral tissues. The short in vivo half-life of GLP-1
      has proven a significant barrier to continued clinical development, and the focus
      of current clinical studies has shifted to agents with longer and more potent in
      vivo activity. This review examines recent exendin-4 pharmacology in the context
      of several known mechanisms of action, and contrasts exendin-4 actions with those
      of GLP-1 and a GLP-1 analogue. One of the most provocative areas of recent
      research is the finding that exendin-4 enhances beta-cell mass, thereby impeding
      or even reversing disease progression. Therefore, a major focus of this is
      article an examination of the data supporting the concept that exendin-4 and GLP
      1 may increase beta-cell mass via stimulation of beta-cell neogenesis,
      stimulation of beta-cell proliferation, and suppression of beta-cell apoptosis.

PMID- 14700745
TI  - The mechanisms of the inhibitory effect of ethanol on gastric emptying involve
      type A CCK receptors.
AB  - The mechanisms involved in the mediation of the inhibitory effects of ethanol on
      gastric emptying were studied in adult male rats. The gastric emptying was
      determined by measuring the amount of phenol red recovered from the stomach after
      intragastric administration. Intragastric administration of a 2.5 g kg(-1) body
      weight dose of ethanol resulted in inhibition of the gastric emptying. Prior
      intraperitoneal treatment with lorglumide (CR-1409), a selective CCK-A receptor
      antagonist, abolished the inhibitory effect of ethanol on the gastric emptying.
      This observation furnishes evidence indicative of the involvement of type A CCK
      receptors in the mediation of the inhibitory effect of large doses of ethanol on
      the gastric emptying.

PMID- 14700744
TI  - Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates
      lipid metabolism to control body fat accrual on a high-fat diet.
AB  - Previous studies have indicated a relationship between cocaine- and amphetamine
      related transcript (CART) and leptin. The present study used quantitative PCR and
      in situ hybridization to examine this CART-leptin relationship in different
      animal models. With CART injection, the function of this pathway was also
      investigated. The results demonstrate that CART mRNA in the arcuate nucleus (ARC)
      was significantly increased in subjects fed a high-fat diet (HFD) compared to low
      fat diet (LFD). It was also elevated in obese vs. lean rats and in normal-weight
      obesity-prone vs. obesity-resistant rats. In each group tested, CART mRNA in the
      ARC was positively correlated specifically with circulating levels of leptin. Its
      close association specifically with leptin was further supported by a stimulatory
      effect of this hormone on CART expression. This leptin-CART relationship in the
      ARC, in contrast, was less consistent or undetectable in the paraventricular
      nucleus and lateral hypothalamus. Central injection of CART peptide (55-102)
      increased circulating non-esterified fatty acid levels and decreased lipoprotein
      lipase activity in adipose tissue. These results suggest that, on a fat-rich
      diet, this leptin-CART pathway originating in the ARC inhibits excessive body fat
      accrual by causing a shift from lipid storage toward lipid mobilization.

PMID- 14700746
TI  - Role of metabolism and receptor responsiveness in the attenuated responses to
      Angiotensin II in mice compared to rats.
AB  - Chronic infusion of Angiotensin II (AngII) to rats is a well-characterized model
      for determining AngII physiology. Genetic manipulations have strengthened
      knowledge of AngII; however, they do not permit an increase in AngII to be
      initiated at a selected age, duration and dose. Therefore, exogenous AngII
      administration remains an important technique to define its biological effect. We
      previously noted that infusion of AngII to mice had minimal effects compared to
      the same dose given to rats. In this study, we compared the effects of chronic
      infusion of the same dose of AngII to C57BL/6 mice and Sprague-Dawley rats, two
      commonly used rodent models. Rats administered AngII exhibited reductions (by
      22%) in body weight, which were not evident in mice. AngII increased blood
      pressure by 54 mm Hg in rats, but had no effect in mice. Vascular histology
      demonstrated that AngII caused medial hypertrophy in rats, with adventitial
      expansion in mice. Plasma concentrations of AngII and its catabolic fragments
      were elevated (twofold) in mice compared to rats. Angiotensin receptor affinity,
      density and distribution were similar in rats and mice. Infusion of AngII
      decreased AngII receptor density in the kidney (by 78%) and spleen (by 29%) of
      mice, but had no effect in rats. AngII produced a sustained contractile response
      in rat aortic strips, but minimal responses in mouse aorta. These results
      demonstrate that differences in circulating angiotensin peptides, AngII receptor
      regulation, and vascular reactivity contribute to diminished responses to AngII
      infusion in mice compared to rats. Results from this study suggest that
      considerably higher doses of AngII may be required to elicit physiologic effects
      of AngII in mice.

PMID- 14700747
TI  - Hypertension induced by nitric oxide synthase inhibition activates the atrial
      natriuretic peptide (ANP) system.
AB  - We assessed the effect of nitric oxide (NO) synthase inhibition on plasma atrial
      natriuretic peptide (ANP) concentration and content in some brain structures
      [neurohypophysis (NH), adenohypophysis (AH), medial basal hypothalamus (MHB) and
      olfactory bulb (OB)] in rats before and after blood volume expansion (BVE). Male
      Wistar rats were injected i.p. with N(pi)-nitro-L-arginine (L-NNA), 25 mg/kg of
      body weight, 40 min before the experiment (acute treatment) or L-NNA at a dose of
      25 mg/kg body weight, twice a day, for 4 days (chronic treatment). The acute
      treatment caused an increase in the blood pressure and plasma ANP concentration
      in rats under basal conditions and after BVE. A decrease in ANP content was
      observed in the OB and NH, whereas no significant changes were found in the AH or
      MBH. In chronically treated rats, we also found an increase in blood pressure and
      in plasma ANP concentration under basal conditions and after BVE. The ANP content
      increased in the OB, NH and AH. These results indicate that systemic NO synthase
      inhibition increases ANP concentration in plasma and in areas of the central
      nervous system. We hypothesize that ANP participates in the hypertension-induced
      by NO synthesis blockade acting by baroreceptors input to the brain to stimulate
      ANP release and synthesis that reduces NO prival hypertension.

PMID- 14700748
TI  - Neurokinin B causes concentration-dependent relaxation of isolated human
      placental resistance vessels.
AB  - Placental neurokinin B (NKB) was recently identified as the causative agent in
      preeclampsia, a condition characterized by increased maternal and feto-placental
      vascular resistance. We hypothesized that NKB should constrict placental
      resistance vessels. Placentas were obtained from normotensive pregnancies.
      Immediately after delivery, stem villous arteries (300 microm diameter, 1.2 mm
      long) were dissected from macroscopically normal tissue in cold HEPES
      physiological salt solution (PSS), mounted on a wire myograph system, and bathed
      in HEPES-PSS at 37 degrees C. After determination of the passive-tension internal
      circumference characteristics, the arteries were set to 90% of the internal
      circumference they would have under a normal physiological transmural pressure.
      Cumulative concentration-response curves were constructed for NKB (1 x 10(-12) to
      1 x 10(-5) mol/l). Since there was no constrictive response to NKB, cumulative
      constrictive concentration-response curves were constructed to the thromboxane
      A(2) mimetic U46619 (1 x 10(-9) to 1 x 10(-5) mol/l). The vessels were then pre
      constricted to 80% of maximal response and exposed to cumulative concentrations
      of NKB (1 x 10(-12) to 1 x 10(-6) mol/l). NKB caused a concentration-dependent
      relaxation (Maximal response NKB, 51+/-5%, n=5; time control, 12+/-6%, n=4;
      P<0.05). Removal of the endothelium did not alter the vasodilatory response to
      NKB. We conclude that, contrary to our hypothesis, NKB causes an endothelium
      independent relaxation of the placental resistance vessels. We propose that NKB
      plays a role in the maintenance of high placental blood flow in normal pregnancy.

PMID- 14700749
TI  - Galanin in pituitary adenomas.
AB  - Tumor galanin content was measured in extracts from human pituitary adenomas
      using a specific RIA method for monitoring human galanin. Twenty-two out of
      twenty-four tumors contained galanin with notably high levels in corticotroph
      adenomas, varying levels in clinically inactive tumors, and low levels in GH
      secreting adenomas. Tumor galanin and ACTH contents were closely correlated in
      all tumors. In four young patients with microadenomas and highly active Mb
      Cushing tumor galanin was inversely related to tumor volume. The molecular form
      of tumor galanin, studied with reverse-phase HPLC, was homogeneous with the
      majority of tumor galanin coeluting with standard human galanin. In the tumors
      analysed with in situ hybridization there was a good correlation between galanin
      peptide levels and galanin mRNA expression. In some tumors galanin mRNA and POMC
      levels coexisted, in others they were essentially in different cell populations.
      Levels of plasma galanin-LI were not related to tumor galanin concentration, and
      galanin levels were in the same range in sinus petrosus close to the pituitary
      venous drainage as in peripheral blood. Corticotrophin releasing hormone
      injections in two patients caused ACTH, but no detectable galanin release into
      sinus petrosus. Our results demonstrate that corticotroph, but not GH adenomas,
      express high levels of galanin, in addition to ACTH, and that in some tumors both
      polypeptides are synthesised in the same cell population. However, galanin levels
      in plasma were not influenced by the tumor galanin content.

PMID- 14700750
TI  - Characterisation and distribution of calcitonin gene-related peptide in a
      primitive teleost, the eel, Anguilla anguilla and comparison with calcitonin.
AB  - Radioimmunoassay (RIA), radioreceptor assay and chromatography were used to study
      the occurrence of calcitonin gene-related peptide (CGRP) in a primitive teleost,
      the eel, Anguilla anguilla. Immunologically and biologically active CGRP-like
      molecules were found in brain, heart, kidney, liver, spleen and ultimobranchial
      body with the higher concentrations in brain, spleen and heart. Gel exclusion
      chromatography of heart and spleen extracts followed by SDS-PAGE showed that the
      eel CGRP-like molecules presented a molecular weight between 3.30 and 3.95 kDa
      similar to that of human CGRP. The wide distribution of CGRP reflects its
      multiple role as brain neuromediator and peripheral paracrine effector as
      described in mammals. In comparison, the distribution of calcitonin (CT) was much
      more restricted, immunologically and biologically active CT-like molecules being
      localised in the ultimobranchial bodies (UBB) that is the site of CT synthesis in
      non-mammalian vertebrates. In plasma, CGRP-like concentrations were 10 to 100
      higher than those of CT. These high concentrations in a primitive teleost
      strengthen the possible endocrine role of CGRP in early vertebrates and emphasise
      the important role of this hormone in evolution.

PMID- 14700752
TI  - [Pediatricians and psychiatrists together beside the hospitalized children:
      between body, feeling and thought].

PMID- 14700751
TI  - A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways
      in vivo.
AB  - Currently, there is no effective pharmacotherapy against exaggerated mobilisation
      of neutrophils in human airway diseases such as chronic obstructive pulmonary
      disease and asthma. We evaluated the effect of two synthetic vasoactive
      intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil
      recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was
      administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague
      Dawley rats. The rats were pretreated either with a VIP synthetic peptide
      analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic
      analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or
      locally. Differential cell counts were performed on bronchoalveolar lavage fluid
      (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in
      separate experiments. Systemic administration of the VIP analogue, the PACAP
      analogue and salbutamol attenuated the cytokine-induced increase in BALf
      neutrophil number. Local administration of the VIP analogue and salbutamol, but
      not the PACAP analogue, also decreased the neutrophil number in BALf. Local
      administration of the VIP analogue and salbutamol caused a transient decrease in
      MAP. Systemic or local administration of a synthetic VIP peptide analogue
      inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action
      is exerted without severe, sustained cardiovascular side effects, and deserves to
      be further evaluated in obstructive pulmonary diseases in human.

PMID- 14700753
TI  - [Child consultation-liaison psychiatry within the hospital: a prospective study].
AB  - The activity of child consultation-liaison psychiatry within the hospital can be
      defined as: the clinical, therapeutic and preventive care given by the staff
      members of the children psychiatric department, and their studies on pedagogy and
      research, in the other departments of the children hospital. MATERIAL AND
      METHODS: Our study focused on the consultation-liaison interventions (N = 215)
      carried out in the Children Hospital of Tours (France) for 1 year (November 1999
      October 2000): it dealt with their characteristics and those of the examined
      population. It aimed at describing qualitatively and quantitatively this activity
      and its evolution, by means of a prospective collection of information, and a
      comparison of some of them with researches carried on previously in the same
      setting. RESULTS: Child consultation-liaison psychiatry plays a major part in
      pediatric hospital today. This activity increased by 33% since 1994. The nature
      of needs for pediatrics care has evolved, and crisis situations are now most
      dominant. Child psychiatry diagnoses are very varied: the most frequent ones
      concern adaptation troubles. The agreement on the suggested medical follow-up
      amounts to more than 50%.

PMID- 14700754
TI  - [High doses of steroids in the management of caustic esophageal burns in
      children].
AB  - Esophageal burns are frequent in some countries. Esophageal stricture is a severe
      complication after caustic ingestion. Its frequency is estimated to 5% and
      reaches 47% in severe esophagitis. AIM OF THE STUDY: To study the influence of
      management of severe esophageal burns with high doses of steroids in the
      occurrence of esophageal stricture through the experience of an endoscopic unit.
      PATIENTS AND METHODS: Twenty-six children with a mean age of 3.5 years (15 months
      8 years) with a second b- (N =22) or a third-degree (N =4) esophageal burns due
      to accidental ingestion of a caustic substance were included between 1993 and
      1999. Corrosive substances ingested were sodium hydroxide (N =17), bleach (N =4),
      alkali (N =3), others (N =2). Upper GI endoscopy was performed in 17 children
      within the 24 hours of caustic ingestion and within the first 48 hours in all
      cases. All patients received methylprednisolone (1 g/1.73 m2/day) plus cimetidine
      and ampicillin plus early oral feeding resumption. RESULTS: Three children (2
      grade II et one grade I) were not controlled on day 30 of the protocol and have
      then been excluded. The remaining 23 children were divided in two groups
      depending on the upper GI endoscopic results: group I of 12 patients completely
      or partially healed and group II of 11 patients who developed an esophageal
      stricture. No difference was observed between the two groups with regard to the
      delay between caustic ingestion and the start of treatment and the number of
      shots of methylprednisolone. Second b- degree esophagitis complicated with an
      esophageal stricture underwent a median of five esophageal dilations (1-12).
      After a median follow-up of three years, four of them have a normal esophagus.
      All children with a third-degree esophagitis developed an esophageal stricture.
      One had a surgical replacement of the esophagus with a segment of colon with good
      outcome. The three others underwent a median of seven esophageal dilations (5
      10). One of them has a normal esophagus after a follow-up of five years while the
      two others were lost to follow-up. CONCLUSION: High dose of corticosteroids seems
      to improve second b-degree esophagitis prognosis and may prevent from esophageal
      stricture.

PMID- 14700755
TI  - [Neonatal lenticulostriate vasculopathy. Mid and longterm outcome (70 cases)].
AB  - OBJECTIVES: If the pattern of neonatal lenticulostriate vasculopathies (NLSV) is
      well-known, the prognosis is unknown except in TORCH syndromes. This study was
      aimed to describe the short, mid and long-term outcome of NLSV of various
      origins. POPULATION AND METHODS: Of 9138 neonates (1981-2000) which were
      submitted to an early brain ultrasound study, 70 presented with a pattern of
      minor (35), moderate (27) or severe (8) NLSV, a single finding in 42 cases and in
      association with minor peri-intraventricular haemorrhage and/or leukomalacias in
      28. The maternal and neonatal charts were reviewed, and the survivors were
      followed according to our usual policy. RESULTS: Of nine deaths, eight cases
      included severe congenital defects (metabolic or malformations or acquired:
      transfused monochorial twins). Of 61 survivors, eight were lost to follow-up
      within the first year, 53 were followed for 21 months to 9 years and 7 months
      (median 4 years 5 months). Of 53 children, 35 (66%) were strictly normal, eight
      had minor deviations, four had moderate and six had major neurodevelopmental
      deficits. Of 34 survivors with isolated NLSV and known follow-up, 27 were normal
      (79%) versus 8/19 (42%) in associated NLSV. CONCLUSIONS: Minor or moderate
      isolated NLSV generally have a good long-term prognosis. Associated forms of any
      severity depend mainly upon the severity of periventricular leukomalacias. Major
      forms of NLSV must be a warning sign of a possible underlying congenital anomaly
      which will rule the vital and functional prognosis.

PMID- 14700756
TI  - [Tachycardia-induced cardiomyopathy in children: a difficult diagnosis but a
      reversible form of left ventricular dysfunction].
AB  - Tachycardia-induced cardiomyopathy is a reversible left ventricular dysfunction
      caused by cardiac arrhythmia. Because of its reversibility, a correct diagnosis
      and treatment are necessary. The aim of our study was to precise the diagnostic
      procedures of the tachycardia-induced cardiomyopathy and to study the left
      ventricular function after the correction of the arrhythmia. PATIENTS AND
      METHODS: A retrospective study done between 1992 and 2001. Children studied were
      followed-up for: an idiopathic form of cardiomyopathy, in which the etiological
      research showed a cardiac arrhythmia; a cardiac arrhythmia associated to a
      cardiomyopathy. An electrocardiogram recorded the cardiac arrhythmia. The left
      ventricular function was evaluated by an echocardiography before and every month
      after the correction of the cardiac arrhythmia. RESULTS: Twelve children were
      included, ages ranged from 2 months to 15 years (median 11 years). Four patients
      presented a cardiac insufficiency associated to arrhythmia; three followed-up for
      an arrhythmia developed a cardiomyopathy; five whose cardiac arrhythmia was not
      easy to demonstrate had an idiopathic form of cardiomyopathy. The Wilcoxon test
      showed a significant amelioration (P < 0.01) of the left ventricular function
      after the correction of the cardiac arrhythmia. CONCLUSIONS: Tachycardia-induced
      cardiomyopathy in children is curable and the diagnosis is quite difficult.
      Pediatricians and family doctors should try to look for specific signs of cardiac
      insufficiency or arrhythmia. Pediatric cardiologists should search a tachycardia
      induced cardiomyopathy in every idiopathic form of cardiomyopathy.

PMID- 14700757
TI  - [Non-Hodgkin's lymphoma with protein S deficiency].
AB  - Venous thrombosis is rare in children. It can be either acquired or of
      constitutional origin. Thrombosis during non-Hodgkin lymphoma remains exceptional
      and is usually locally associated to the tumoral process, raising the issue of
      its tumoral or cruoric nature. The treatment is based on anticoagulation
      concomitantly to chemotherapy. We report on a 4-year-old boy admitted for
      mediastinal non-Hodgkin lymphoma, who developed a thrombosis of the superior vena
      cava associated to protein S-deficiency. The mechanism of thrombosis may have
      been multifactorial: associated protein S-deficiency, vascular compression,
      tumoral process and chemotherapy.

PMID- 14700758
TI  - [Macrocephaly and multiple hamartoma: a very variable entity].
AB  - The Bannayan-Zonana is a dominant autosomal polymalformation syndrome. CASE
      REPORT: We report a case of Bannayan-Zonana syndrome in a 3-year-old girl, who
      presented with macrocephaly and a cervical lipoma. The patient's mother had
      neurofibromatosis I. No mutation in the PTEN gene was found. The slowly
      progressive lipoma increased with age and the surgical reduction was necessary.
      COMMENTARIES: Macrocephaly is constant in different syndromes characterized with
      multiple hamartomas. The multiple hamartomas syndrome represents an entity with a
      high variability of expression.

PMID- 14700759
TI  - [Morganella morganii and early-onset neonatal infection].
AB  - Morganella morganii is an opportunistic gram-negative bacterium, resistant to
      ampicillin, and scarcely involved in early-onset neonatal sepsis. CASE REPORT:
      After a premature rupture of the membranes, a pregnant patient received
      prophylactic amoxicillin per os. She developed chorioamnionitis. Her infant was
      diagnosed with early-onset sepsis. Maternal and baby's blood cultures grew M.
      morganii. Both the mother and the infant were successfully treated with a third
      generation cephalosporin and an aminoglycoside. DISCUSSION: The influence of a
      prior antibiotherapy on the emergence of M. morganii vertical infections is
      discussed.

PMID- 14700760
TI  - [Surgical aspects of intussusception due to lymphoma in children].
AB  - BACKGROUND: Intussusception due to lymphoma is a challenging condition for
      pediatric surgeons. The aim of this study is to report seven cases of this entity
      and to discuss its management. CASE REPORT: Six boys and one girl, 3-15-years
      old, were admitted for intussusception secondary to a lymphoma. All patients
      underwent laparotomy: biopsy of massive abdominal tumor 6 and 8 weeks following
      resection of an intussusception (two cases), ileal resection of non-reductible
      intussusception (one case), right hemicolectomy for tumor of the appendix (one
      case), tumorectomy of localized ileal tumor (two cases), enlarged mesenteric
      lymph node biopsy associated with simple reduction of intussusception (one case).
      All children were successfully treated with protocol chemotherapy with a 15-month
      to 13-year follow-up. No relapse was observed. CONCLUSION: Surgeons should be
      aware of operative sights of ileal lymphomas. Diagnosis of lymphoma may be
      difficult after manual reduction of intussusception. A sample of any abnormality
      (mesenteric lymph node, peritoneal fluid) should be taken. Intestinal resection
      allows to reduce the intensity of chemotherapy but must be as limited as
      possible: ileal resection in cases of complicated intussusception, tumorectomy
      "in sano" in cases of ileal parietal isolated tumor. Reduction of intussusception
      alone (with no resection of ileal tumor) seems to be effective if diagnosis of
      lymphoma is possible from peripheral samples (peritoneal fluid, pleural effusion,
      mesenteric lymph node, bone marrow biopsy...).

PMID- 14700761
TI  - [Pediatric emergency department policy. Implementation and management of the
      resuscitation room].
AB  - The pediatric resuscitation room is the place where children suffering from vital
      distress are cared for in the emergency unit. Recommendations for its
      organization, functioning and evaluation have been ruled on by experts from six
      medical societies involved in these emergencies. They concern all the hospital's
      physicians, nurses and administrative directors.

PMID- 14700762
TI  - [Radiologic case of the month. Pulmonary atresia discovered at age 10].

PMID- 14700763
TI  - [Clinical and biological aspects of severe malaria in childhood in a tropical
      hospital, in Abidjan, (Cote-d'Ivoire)].

PMID- 14700764
TI  - [Medullary sponge kidney 13-year-old boy].

PMID- 14700765
TI  - [May Plasmodium falciparum induce a hemolytic uremic syndrome?].

PMID- 14700766
TI  - [Clinical course (ten years) of sickle cell disease in Martinique after neonatal
      screening].

PMID- 14700767
TI  - [Contribution to the study of the congenital anomalies at the Albert-Royer
      paediatric hospital of Dakar].

PMID- 14700768
TI  - [The newborn foot abnormalities].

PMID- 14700769
TI  - [Medical treatments of hyperactive child].
AB  - Treatment of hyperactive child is multimodal, a combination of behaviour therapy
      and medication. Stimulant drugs are the most often prescribed medications. In
      France, we use methylphenidate (Ritaline); its efficacy was demonstrated with
      mild side effects. New formulations of methylphenidate with prolonged action, and
      non-psychostimulant treatment (atomoxetine) are available in some countries, but
      not yet in France.

PMID- 14700770
TI  - [Analgesia in the pediatric emergency department].
AB  - Pain concerns more than 50% of the children cared in the emergency unit. After
      evaluation, it has to be cured with drugs adapted to its level and its origin.
      Residual pain needs therapeutic adjustment. The goal is to allow the child to
      restart his activities. A preventive sedation analgesia is necessary when a
      painful exam is to be performed, either for diagnosis or therapeutic purpose. For
      this goal ideal analgesics, either for monotherapy or associated, are easily and
      painlessly administered. They have rapid onset of action, brief half-life,
      predictable, effective analgesic properties without side effects and they are
      quickly reversible. These drugs do not exist and every sedation procedure has a
      risk of hypoxemia. With the human and equipment's investment an emergency
      department should be able to ensure that procedures are performed in children
      under sedation with a standard of safety that is similar to general anaesthesia.
      The main drawback in a well-organised system should be a significant children's
      rate for which general anaesthesia is preferred.

PMID- 14700771
TI  - [Raynaud's phenomenon in children].
AB  - Raynaud's phenomenon has been described more than 140 years ago, its prevalence
      in the general population is high, and yet the underlying pathological mechanisms
      are only partly understood. In children, female preponderance has been reported,
      as it is also the case in adults, and the disease usually starts after the age of
      10. Diagnosis and differential diagnosis, in particular with erythromelalgia, are
      usually made through patient's or parent's interrogatory. It is important to
      distinguish primary Raynaud's phenomenon, which is usually benign, from Raynaud's
      phenomenon secondary to connective tissue disease. To this regard, nailfold
      capillaroscopy is of great help, as may be more recently introduced techniques
      such as thermography and digital blood pressure response to cooling. Primary
      Raynaud's phenomenon usually only requires simple physical measures (avoidance of
      exposure to coldness, gloves in winter, ...) plus sometimes oral calcium
      blockers. By contrast, Raynaud's phenomenon secondary to connective tissue
      disease requires systemic investigations, assessment and treatment of the
      underlying disease and, in some cases, more aggressive treatments such as
      intravenous carboprostacyclin (Iloprost).

PMID- 14701664
TI  - Streptozotocin-induced diabetes impairs Mg2+ homeostasis and uptake in rat liver
      cells.
AB  - Male Sprague-Dawley rats rendered diabetic by streptozotocin injection presented
      10 and 20% decreases in total hepatic Mg2+ content at 4 and 8 wk, respectively,
      following diabetes onset. This decrease was associated with a parallel decrease
      in K+ and ATP content and an increase in Na+ level. In diabetic liver cells, the
      Mg2+ extrusion elicited by alpha1-adrenoceptor stimulation was markedly reduced
      compared with nondiabetic livers, whereas that induced by beta-adrenoceptor
      stimulation was unaffected. In addition, diabetic hepatocytes did not accumulate
      Mg2+ following stimulation of protein kinase C pathway by vasopressin,
      diacylglycerol analogs, or phorbol 12-myristate 13-acetate derivates despite the
      reduced basal content in cellular Mg2+. Experiments performed in purified plasma
      membrane from diabetic livers located the defect at the level of the
      bidirectional Na+/Mg2+ exchanger operating in the basolateral domain of the
      hepatocyte cell membrane, which could extrude but not accumulate Mg2+ in exchange
      for Na+. The impairment of Mg2+ uptake mechanism, in addition to the decrease in
      cellular ATP level, can contribute to explaining the decrease in liver Mg2+
      content observed under diabetic conditions.

PMID- 14701665
TI  - Altered expression of nuclear hormone receptors and coactivators in mouse heart
      during the acute-phase response.
AB  - Severe sepsis results in the decreased uptake and oxidation of fatty acids in the
      heart and cardiac failure. Some of the key proteins required for fatty acid
      uptake and oxidation in the heart have been shown to be downregulated after
      endotoxin (LPS) administration. The nuclear hormone receptors, peroxisome
      proliferator-activated receptor (PPAR) and thyroid receptor (TR), which
      heterodimerize with the retinoid X receptor (RXR), are important regulators of
      fatty acid metabolism and decrease in the liver after LPS administration. In the
      present study, we demonstrate that LPS treatment produces a rapid and marked
      decrease in the mRNA levels of all three RXR isoforms, PPARalpha and PPARdelta,
      and TRalpha and TRbeta in the heart. Moreover, LPS administration also decreased
      the expression of the coactivators CREB-binding protein (CBP)/p300, steroid
      receptor coactivator (SRC)-1, SRC-3, TR-associated protein (TRAP)220, and
      PPARgamma coactivator (PGC)-1, all of which are required for the transcriptional
      activity of RXR-PPAR and RXR-TR. In addition, the mRNA levels of the target genes
      malic enzyme, Spot 14, sarcoplasmic reticulum Ca2+-ATPase, or SERCA2, the VLDL
      receptor, fatty acyl-CoA synthetase, fatty acid transporter/CD36, carnitine
      palmitoyltransferase Ibeta, and lipoprotein lipase decrease in the heart after
      LPS treatment. The decrease in expression of RXRalpha, -beta, and -gamma,
      PPARalpha and -delta, and TRalpha and -beta, and of the coactivators CBP/p300,
      SRC-1, SRC-3, TRAP220, and PGC-1 and the genes they regulate, induced by LPS in
      the heart, could account for the decreased expression of key proteins required
      for fatty acid oxidation and thereby play an important role in cardiac
      contractility. These alterations could contribute to the myocardial dysfunction
      that occurs during sepsis.

PMID- 14701669
TI  - Deletion of the Nhlh2 transcription factor decreases the levels of the
      anorexigenic peptides alpha melanocyte-stimulating hormone and thyrotropin
      releasing hormone and implicates prohormone convertases I and II in obesity.
AB  - Body weight is controlled by the activation of signal transduction pathways in
      both the brain and peripheral tissues. Interestingly, although many hypothalamic
      neuropeptides and receptors have been implicated in the regulation of body
      weight, the transcriptional and posttranscriptional mechanisms through which
      these genes are expressed in response to changes in energy balance remain
      unclear. Our laboratory studies a mouse in which targeted deletion of the
      neuronal basic helix-loop-helix (bHLH) transcription factor, nescient helix-loop
      helix 2 protein (Nhlh2), results in adult-onset obesity. The aim of this work was
      to use the phenotype of the Nhlh2 knockout mouse and the expression pattern of
      Nhlh2 to identify genes that are regulated by this transcription factor. In this
      article, we show that Nhlh2 is expressed throughout the adult hypothalamus. Using
      dual-label in situ hybridization, we demonstrate that, in the arcuate nucleus of
      the adult hypothalamus (ARC), Nhlh2 expression can be found in rostral
      proopiomelanocortin (POMC) neurons, whereas in the paraventricular nucleus (PVN),
      Nhlh2 is expressed in TRH neurons. In addition, we find that hypothalamic POMC
      derived alphaMSH in the ARC and TRH in the PVN are regulated
      posttranscriptionally via Nhlh2-mediated control of prohormone convertase I and
      II mRNA levels. This is the first report in which regulation of body weight is
      linked to the action of a neuronal bHLH transcription factor on prohormone
      convertase mRNA levels. Furthermore, this work supports a direct role for
      transcriptional control of neuropeptide processing enzymes in the etiology of
      adult-onset obesity.

PMID- 14701670
TI  - Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and
      cholesterol in rats and primates: selective actions relative to 3,5,3'-triiodo-L
      thyronine.
AB  - Current drug therapies for obesity are ineffective, and existing treatments for
      lipid disorders can be further improved. Thyroid hormones affect both conditions,
      although currently available nonselective thyromimetics are not clinically useful
      for such treatment due to cardiac side effects. Recent studies suggest that
      thyroid hormone receptor subtype beta (TRbeta) selective agonists have a profile
      in which cholesterol can be reduced with minimal tachycardia. The purpose of this
      study was to determine whether modest (5-10%) increases in metabolic rate could
      also be observed with minimal tachycardia after TRbeta stimulation. For these
      studies, the TRbeta selective agonist, GC-1, was used to assess selectivity for
      lipid-lowering and metabolic rate changes relative to tachycardia. Studies in
      cholesterol-fed rats (7 d treatment) showed that GC-1 reduced cholesterol (ED(50)
      = 190 nmol/kg x d) approximately 30 times more potently than it induced
      tachycardia (ED(15) = 5451 nmol/kg x d). T(3) showed no potency difference
      between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold
      selectivity for increasing metabolic rate (ED(5) = 477 nmol/kg x d) relative to
      tachycardia compared with T(3), which showed no selectivity. In cynomolgus
      monkeys treated for 7 d, significant cholesterol-lowering and lipoprotein (a)
      reduction was noted for both T(3) and GC-1, whereas no tachycardia was observed
      for GC-1, unlike T(3). T(3) and GC-1 caused a significant (approximately 4%)
      reduction in body weight in these animals. Therefore, selective TRbeta activation
      may be a potentially usefully treatment for obesity and reduction of low density
      lipoprotein cholesterol and reduction of the atherogenic risk factor lipoprotein
      (a).

PMID- 14701671
TI  - Effect of pituitary adenylate cyclase-activating polypeptide and vasoactive
      intestinal polypeptide on mouse preantral follicle development in vitro.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide
      isolated from ovine hypothalamus. It is transiently expressed in preovulatory
      follicles and positively affects several parameters correlated with the ovulatory
      process. It has also been shown to be expressed in the interstitial tissue around
      primordial and preantral follicles. The aim of the present study was to
      investigate whether PACAP influences preantral follicle growth and
      differentiation. Mouse preantral follicles were cultured for 5 d in the presence
      of FSH and increasing concentrations of PACAP or vasoactive intestinal
      polypeptide (VIP) (10(-12) to 10(-7) m). In the presence of FSH, follicles
      increased in diameter and formed an antrum. At the concentrations tested, neither
      PACAP alone nor VIP alone had any effect on follicle development, but the
      addition of either peptide to FSH-stimulated follicles caused a dose-dependent
      inhibition of follicle growth, antrum formation, granulosa cell proliferation,
      and estradiol production. The effect of PACAP on follicle growth and antrum
      formation was directly correlated with the length of stimulation and was
      reversible. Although exposure of follicles to 10(-7) m PACAP and VIP did not
      affect oocyte growth, it severely impaired completion of meiotic maturation in
      oocytes isolated from the follicles and cultured for 17 h in medium alone. The
      cyclic production of PACAP by preovulatory follicles during the estrous cycle in
      adult rats and its induction by LH in the rat and mouse ovary suggest that this
      peptide may play a role in the local regulation of preantral follicle growth.

PMID- 14701672
TI  - Skeletal abnormalities in Pth-null mice are influenced by dietary calcium.
AB  - We have examined the role of PTH in the postnatal state in a mouse model of PTH
      deficiency generated by targeting the Pth gene in embryonic stem cells. Mice
      homozygous for the ablated allele, when maintained on a normal calcium intake,
      developed hypocalcemia, hyperphosphatemia, and low circulating 1,25
      dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels consistent with primary
      hypoparathyroidism. Bone turnover was reduced, leading to increased trabecular
      and cortical bone volume in PTH-deficient mice. When mutant mice were placed on a
      low-calcium diet, renal 25-hydroxyvitamin D 1 alpha-hydroxylase expression
      increased despite the absence of PTH, leading to a rise in circulating
      1,25(OH)(2)D(3) levels, marked osteoclastogenesis, and profound bone resorption.
      These studies demonstrate the dependence of the skeletal phenotype in animals
      with genetically depleted PTH on the external environment as well as on internal
      hormonal and ionic circulatory factors. They also show that, although PTH action
      is the first defense against hypocalcemia, 1,25(OH)(2)D(3) can be mobilized, even
      in the absence of PTH, to guard against extreme calcium deficiency.

PMID- 14701673
TI  - Inhibition of phosphorylation of a forkhead transcription factor sensitizes human
      ovarian cancer cells to cisplatin.
AB  - The Forkhead family transcription factor FKHRL1 is an inducer of apoptosis in its
      unphosphorylated form and was recently reported to be a substrate of Akt kinase.
      We studied the roles of FKHRL1 in both cisplatin-resistant Caov-3 (a papillary
      adenocarcinoma cell line) and cisplatin-sensitive A2780 human ovarian cancer cell
      lines. Treatment of Caov-3 cells but not A2780 cells with cisplatin transiently
      stimulated the phosphorylation of FKHRL1. Transfection experiments revealed that
      a kinase inactive-mutant of Akt or a triple mutant (TM) of FKHRL1, in which all
      three of the putative Akt phosphorylation sites were converted to alanine, was
      unable to phosphorylate the FKHRL1 protein in cells treated with cisplatin.
      Because the phosphorylated form of FKHRL1 is known to be localized in the
      cytoplasm, we examined whether cisplatin-induced phosphorylation of FKHRL1 might
      have an effect on the subcellular distribution of FKHRL1. Cisplatin induced the
      localization of FKHRL1 in the cytoplasm in Caov-3 cells but not in A2790 cells.
      Moreover, cisplatin induced the association of 14-3-3 protein with phosphorylated
      FKHRL1 in Caov-3 cells but not in A2790 cells. Because the unphosphorylated form
      of FKHRL1 binds the Fas ligand promoter, thereby inducing apoptosis, we further
      examined the effect of the phosphorylation status of FKHRL1 on the activity of
      the Fas ligand promoter in the presence of cisplatin. Transfection with the
      kinase-inactive mutant of Akt or TM of FKHRL1 induced the activity of the Fas
      ligand promoter in Caov-3 cells. Moreover, exogenous expression of TM of FKHRL1
      in Caov-3 cells decreased the cell viability after treatment with cisplatin. Our
      findings suggest that cisplatin causes the phosphorylation of FKHRL1 via a
      phosphatidylinositol 3-kinase/Akt cascade, and inhibition of this cascade
      sensitizes ovarian cancer cells to cisplatin.

PMID- 14701674
TI  - Long-term treatment of anterior pituitary cells with nitric oxide induces
      programmed cell death.
AB  - Nitric oxide (NO) plays a complex role in modulating programmed cell death. It
      can either protect the cell from apoptotic death or mediate apoptosis, depending
      on its concentration and the cell type and/or status. In this study, we
      demonstrate that long-term exposition to NO induces cell death of anterior
      pituitary cells from Wistar female rats. DETA NONOate (Z)-1-[2-(2-aminoethyl)-N
      (2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, 1 mm], a NO donor that releases
      NO for an extended period of time, decreased cellular viability and prolactin
      release from primary cultures of anterior pituitary cells. Morphological studies
      showed an increase in the number of cells with chromatin condensation and nuclear
      fragmentation at 24 and 48 h after DETA/NO exposure. DNA internucleosomal
      fragmentation was also observed at the same time. Reversibility of the NO effect
      on cellular viability and prolactin release was observed only when the cells were
      incubated with DETA/NO for less than 6 h. Most apoptotic cells were
      immunopositive for prolactin, suggesting a high susceptibility of lactotrophs to
      the effect of NO. The cytotoxic effect of NO is dependent of caspase-9 and
      caspase-3, but seems to be independent of oxidative stress or nitrosative stress.
      Our results show that the exposition of anterior pituitary cells to NO for long
      periods induces programmed cell death of anterior pituitary cells.

PMID- 14701675
TI  - A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist
      demonstrates favorable effects on lipid homeostasis.
AB  - Patients with type 2 diabetes mellitus exhibit hyperglycemia and dyslipidemia as
      well as a markedly increased incidence of atherosclerotic cardiovascular disease.
      Here we report the characterization of a novel arylthiazolidinedione capable of
      lowering both glucose and lipid levels in animal models. This compound,
      designated TZD18, is a potent agonist with dual human peroxisome proliferator
      activated receptor (PPAR)-alpha/gamma activities. In keeping with its PPARgamma
      activity, TZD18 caused complete normalization of the elevated glucose in db/db
      mice and Zucker diabetic fatty rats. TZD18 lowered both cholesterol and
      triglycerides in hamsters and dogs. TZD18 inhibited cholesterol biosynthesis at
      steps before mevalonate and reduced hepatic levels of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase activity. Moreover, TZD18 significantly suppressed gene
      expression of fatty acid synthesis and induced expression of genes for fatty acid
      degradation and triglyceride clearance. Studies on 17 additional PPARalpha or
      PPARalpha/gamma agonists showed that lipid lowering in hamsters correlated with
      the magnitude of hepatic gene expression changes. Importantly, the presence of
      PPARgamma agonism did not affect the relationship between hepatic gene expression
      and lipid lowering. Taken together, these data suggest that PPARalpha/gamma
      agonists, such as TZD18, affect lipid homeostasis, leading to an antiatherogenic
      plasma lipid profile. Agents with these properties may provide favorable means
      for treatment of type 2 diabetes and dyslipidemia and the prevention of
      atherosclerotic cardiovascular disease.

PMID- 14701676
TI  - Tissue-type plasminogen activator and its inhibitor plasminogen activator
      inhibitor type 1 are coordinately expressed during ovulation in the rhesus
      monkey.
AB  - Ovulation is a gonadotropin-controlled process that is essential for the
      propagation of all mammalian species. In the present study, we used a pregnant
      mare serum gonodotropin/human chorionic gonadotropin (hCG)-induced, synchronized
      ovulation model in rhesus monkeys and systematically investigated the roles of
      the plasminogen activator (PA) system in the ovulatory process of the primate. At
      different follicular developmental stages throughout the periovulatory period,
      samples of ovaries, granulosa cells, and theca-interstitial cells as well as
      follicular fluid were collected, and levels of PA and PA inhibitor type-1 (PAI-1)
      were evaluated by fibrin overlay, reverse fibrin overlay, Northern blot analysis,
      and in situ hybridization, respectively. We showed that in response to an
      injection of ovulation-triggering hCG, which mimics the preovulatory surge of LH
      in the circulation, granulosa cell-derived tissue-type PA (tPA) was substantially
      elevated in preovulatory follicles and reached its maximum level just before
      ovulation. Although theca-interstitial cell-derived PAI-1 was also stimulated by
      pregnant mare serum gonodotropin and hCG treatments, however, the maximum level
      of PAI-1 appeared 12 h earlier than that of tPA. When ovulation approached,
      accompanying the highest tPA level in the preovulatory follicles, the follicular
      PAI-1 level declined dramatically to its minimum value. Moreover, our data on the
      expression of follicular PA and PAI-1 over the periovulatory period were
      reinforced by results obtained at the mRNA level. Our data suggest that the
      coordinated expression of tPA and PAI-1 may be of importance for the follicular
      rupture process during ovulation in the primate.

PMID- 14701677
TI  - Physiological studies of transgenic mice overexpressing growth hormone (GH)
      secretagogue receptor 1A in GH-releasing hormone neurons.
AB  - The type 1A GH secretagogue (GHS) receptor (GHSR) has been proposed to mediate
      the effects of ghrelin on GH release, food intake, and body composition. We have
      overexpressed GHSR in GH-producing GC cells and GHRH neurons in an attempt to
      enhance signaling via this pathway selectively, in the GH axis. Constitutive
      overexpression of human GHSR in rat GC cell lines resulted in increased basal
      phosphoinositol turnover and rendered them responsive to GHS ligands. We then
      generated transgenic mice overexpressing human GHSR in GHRH neurons using a 38-kb
      rat GHRH cosmid promoter. GHRH-GHSR transgenic mice showed increased hypothalamic
      GHRH expression, pituitary GH contents, and postweaning growth rates. Body
      weights of the transgenic mice became similar in adulthood, whereas adipose mass
      was reduced, particularly so in female GHRH-GHSR mice. Organ and muscle weights
      of transgenic mice were increased despite chronic exposure to a high fat diet.
      These results suggest that constitutive overexpression of GHSR in GHRH neurons up
      regulates basal activity in the GHRH-GH axis. However, GHRH-GHSR mice showed no
      evidence of increased sensitivity to acute or chronic treatment with exogenous
      GHS ligands. Food intake and adipose tissue responses to chronic high fat feeding
      and treatment with GHS ligands were unaffected, as were locomotor and anxiety
      behaviors, although GHRH-GHSR mice remained significantly leaner than wild-type
      littermates. Thus, constitutive overexpression of GHSR can up-regulate basal
      signaling activity in the GHRH/GH axis and reduce adiposity without affecting
      other GHSR-mediated signals.

PMID- 14701678
TI  - Identification of the adrenocorticotropin and ginkgolide B-regulated 90
      kilodalton protein (p90) in adrenocortical cells as a serotransferrin precursor
      protein homolog (adrenotransferrin).
AB  - Two-dimensional electrophoresis (2D-PAGE) of metabolically labeled adrenocortical
      proteins, identified a series of spots at a molecular size of 90 kDa [isoelectric
      point (pI) 6.8-7.1; p90] that was induced by ACTH, but whose intensity was
      reduced in cells obtained from animals treated with an extract of Ginkgo biloba
      (EGb 761) and its purified component ginkgolide B (GKB). We have now identified
      p90. GKB (2 mg/kg x d, i.p.) was administered to rats for 8 d. Adrenocortical
      cells were prepared and stimulated with ACTH for 3 h. Cells obtained from saline
      treated rats responded to ACTH by producing high amounts of corticosterone, an
      effect that was inhibited in cells obtained from GKB-treated animals. Samples
      were fractionated by 2D-PAGE and matrix-assisted laser desorption ionization mass
      spectrometry analysis of the p90 spots isolated from the gels revealed sequences
      sharing identity with the serotransferrin precursor protein. Further PCR
      screening of a rat adrenal cDNA library identified a sequence with a high degree
      of homology (79%) to serotransferrin precursor protein, and a lesser degree to
      rat transferrin (54%) and human melanotransferrin (32.8%). p90, in 2D-PAGE
      immunoblots, was also recognized by a monoclonal antibody raised against human 97
      kDa melanotransferrin. Iron binding assays with rat adrenal cortex extracts
      further identified a 90-kDa melanotransferrin immunoreactive protein binding
      iron, suggesting that the identified protein, which we name "adrenotransferrin,"
      may have iron-binding activity. This is the first report describing the presence
      of a serotransferrin precursor protein homolog belonging to the transferrin
      family and sharing epitopes with melanotransferrin in the adrenal, its induction
      by ACTH, and sensitivity to GKB.

PMID- 14701679
TI  - LRR-containing receptors regulating plant development and defense.
AB  - Despite the presence of more than 400 genes that encode receptor-like kinases
      (RLKs) in the Arabidopsis thaliana genome, very little is known about the range
      of biological processes that they control, or the mechanisms by which they
      function. This review focuses on the most recent findings from studies of several
      leucine-rich-repeat (LRR) class RLKs in A. thaliana, and their implications for
      our understanding of plant receptor function and signaling. We compare the
      biological functions of plant and animal LRR-containing receptors, and the
      potential commonalities in the signaling mechanisms employed.

PMID- 14701680
TI  - Multiple signaling pathways and a selector protein sequentially regulate
      Drosophila wing development.
AB  - Drosophila wing development is a useful model to study organogenesis, which
      requires the input of selector genes that specify the identity of various
      morphogenetic fields (Weatherbee, S. D. and Carroll, S. B. (1999) Cell 97, 283
      286) and cell signaling molecules. In order to understand how the integration of
      multiple signaling pathways and selector proteins can be achieved during wing
      development, we studied the regulatory network that controls the expression of
      Serrate (Ser), a ligand for the Notch (N) signaling pathway, which is essential
      for the development of the Drosophila wing, as well as vertebrate limbs. Here, we
      show that a 794 bp cis-regulatory element located in the 3' region of the Ser
      gene can recapitulate the dynamic patterns of endogenous Ser expression during
      wing development. Using this enhancer element, we demonstrate that Apterous (Ap,
      a selector protein), and the Notch and Wingless (Wg) signaling pathways, can
      sequentially control wing development through direct regulation of Ser expression
      in early, mid and late third instar stages, respectively. In addition, we show
      that later Ser expression in the presumptive vein cells is controlled by the Egfr
      pathway. Thus, a cis-regulatory element is sequentially regulated by multiple
      signaling pathways and a selector protein during Drosophila wing development.
      Such a mechanism is possibly conserved in the appendage outgrowth of other
      arthropods and vertebrates.

PMID- 14701681
TI  - Dd-STATb, a Dictyostelium STAT protein with a highly aberrant SH2 domain,
      functions as a regulator of gene expression during growth and early development.
AB  - Dictyostelium, the only known non-metazoan organism to employ SH2
      domain:phosphotyrosine signaling, possesses STATs (signal transducers and
      activators of transcription) and protein kinases with orthodox SH2 domains. Here,
      however, we describe a novel Dictyostelium STAT containing a remarkably divergent
      SH2 domain. Dd-STATb displays a 15 amino acid insertion in its SH2 domain and the
      conserved and essential arginine residue, which interacts with phosphotyrosine in
      all other known SH2 domains, is substituted by leucine. Despite these
      abnormalities, Dd-STATb is biologically functional. It has a subtle role in
      growth, so that Dd-STATb-null cells are gradually lost from the population when
      they are co-cultured with parental cells, and microarray analysis identified
      several genes that are either underexpressed or overexpressed in the Dd-STATb
      null strain. The best characterised of these, discoidin 1, is a marker of the
      growth-development transition and it is overexpressed during growth and early
      development of Dd-STATb null cells. Dimerisation of STAT proteins occurs by
      mutual SH2 domain:phosphotyrosine interactions and dimerisation triggers STAT
      nuclear accumulation. Despite its aberrant SH2 domain, the Dd-STATb protein
      sediments at the size expected for a homodimer and it is constitutively enriched
      in the nucleus. Moreover, these properties are retained when the predicted site
      of tyrosine phosphorylation is substituted by phenylalanine. These observations
      suggest a non-canonical mode of activation of Dd-STATb that does not rely on
      orthodox SH2 domain:phosphotyrosine interactions.

PMID- 14701682
TI  - Androgen receptor function is required in Sertoli cells for the terminal
      differentiation of haploid spermatids.
AB  - Androgen receptor function is required for male embryonic sexual differentiation,
      pubertal development and the regulation of spermatogenesis in mammals. During
      spermatogenesis, this requirement is thought to be mediated by Sertoli cells and
      its genetic and pharmacological disruption is manifested in spermatocytes as
      meiotic arrest. Through studies of a hypomorphic and conditional allele of the
      androgen receptor (Ar) gene, we have uncovered a dual post-meiotic requirement
      for androgen receptor activity during male germ cell differentiation.
      Observations in Ar hypomorphic animals demonstrate that terminal differentiation
      of spermatids and their release from the seminiferous epithelium is AR dependent
      and maximally sensitive to AR depletion within the testis. Cell-specific
      disruption of Ar in Sertoli cells of hypomorphic animals further shows that
      progression of late-round spermatids to elongating steps is sensitive to loss of
      Sertoli cell AR function, but that progression through meiosis and early-round
      spermatid differentiation are surprisingly unaffected.

PMID- 14701683
TI  - The planar cell polarity protein Strabismus promotes Pins anterior localization
      during asymmetric division of sensory organ precursor cells in Drosophila.
AB  - Cell fate diversity is generated in part by the unequal segregation of cell-fate
      determinants during asymmetric cell division. In the Drosophila bristle lineage,
      the sensory organ precursor (pI) cell is polarized along the anteroposterior (AP)
      axis by Frizzled (Fz) receptor signaling. We show here that Fz localizes at the
      posterior apical cortex of the pI cell prior to mitosis, whereas Strabismus
      (Stbm) and Prickle (Pk), which are also required for AP polarization of the pI
      cell, co-localize at the anterior apical cortex. Thus, asymmetric localization of
      Fz, Stbm and Pk define two opposite cortical domains prior to mitosis of the pI
      cell. At mitosis, Stbm forms an anterior crescent that overlaps with the
      distribution of Partner of Inscuteable (Pins) and Discs-large (Dlg), two
      components of the anterior Dlg-Pins-Galphai complex that regulates the
      localization of cell-fate determinants. At prophase, Stbm promotes the anterior
      localization of Pins. By contrast, Dishevelled (Dsh) acts antagonistically to
      Stbm by excluding Pins from the posterior cortex. We propose that the Stbm
      dependent recruitment of Pins at the anterior cortex of the pI cell is a novel
      read-out of planar cell polarity.

PMID- 14701686
TI  - Neutrophil PRV-1 expression across the chronic myeloproliferative disorders and
      in secondary or spurious polycythemia.
AB  - Recent studies have demonstrated neutrophil overexpression of the polycythemia
      rubra vera-1 (PRV-1) gene in polycythemia vera (PV) but not in secondary or
      spurious polycythemia (SP). To validate as well as expand upon this novel
      observation, we conducted a prospective study of 88 subjects: 30 with PV, 22 with
      SP, 14 with essential thrombocythemia (ET), 12 with myelofibrosis with myeloid
      metaplasia (MMM), and 10 controls. To minimize interstudy methodologic
      differences, we used a published real-time polymerase chain reaction (PCR)-based
      assay. The proportion of patients with increased neutrophil PRV-1 expression was
      83% in PV, 21% in ET, 42% in MMM, 18% in SP, and 0% in controls. All 5 MMM
      patients with PRV-1 up-regulation had an antecedent history of PV. We conclude
      that neutrophil PRV-1 up-regulation is a characteristic feature of PV that may
      not be affected by fibrotic transformation. However, quantifying neutrophil PRV-1
      mRNA, while complementary to other tests, is not in itself sufficient for the
      diagnosis of PV.

PMID- 14701687
TI  - Interleukin-6 deficiency affects bone marrow stromal precursors, resulting in
      defective hematopoietic support.
AB  - Interleukin-6 (IL-6) is a critical factor in the regulation of stromal function
      and hematopoiesis. In vivo bromodeoxyuridine incorporation analysis indicates
      that the percentage of Lin(-)Sca-1(+) hematopoietic progenitors undergoing DNA
      synthesis is diminished in IL-6-deficient (IL-6(-/-)) bone marrow (BM) compared
      with wild-type BM. Reduced proliferation of IL-6(-/-) BM progenitors is also
      observed in IL-6(-/-) long-term BM cultures, which show defective hematopoietic
      support as measured by production of total cells, granulocyte macrophage-colony
      forming units (CFU-GMs), and erythroid burst-forming units (BFU-Es). Seeding
      experiments of wild-type and IL-6(-/-) BM cells on irradiated wild-type or IL-6
      deficient stroma indicate that the hematopoietic defect can be attributed to the
      stromal and not to the hematopoietic component. In IL-6(-/-) BM, stromal
      mesenchymal precursors, fibroblast CFUs (CFU-Fs), and stroma-initiating cells
      (SICs) are reduced to almost 50% of the wild-type BM value. Moreover, IL-6(-/-)
      stromata show increased CD34 and CD49e expression and reduced expression of the
      membrane antigens vascular cell adhesion molecule-1 (VCAM-1), Sca-1, CD49f, and
      Thy1. These data strongly suggest that IL-6 is an in vivo growth factor for
      mesenchymal precursors, which are in part implicated in the reduced longevity of
      the long-term repopulating stem cell compartment of IL-6(-/-) mice.

PMID- 14701690
TI  - Targeting lentiviral vector expression to hepatocytes limits transgene-specific
      immune response and establishes long-term expression of human antihemophilic
      factor IX in mice.
AB  - Stable gene replacement by in vivo administration of lentiviral vectors (LVs) has
      therapeutic potential for metabolic disorders and other systemic diseases. We
      studied the expression of intracellular and secreted proteins by LVs in
      immunocompetent mice. Liver, spleen, and bone marrow cells were efficiently
      transduced. However, transgene expression, driven by a ubiquitous promoter, was
      limited by transgene-specific cellular and humoral immune responses, leading to
      the clearance of transduced cells. After green fluorescent protein (GFP) gene
      transfer, the liver showed infiltration of CD8(+) cytotoxic T cells, and GFP
      specific CD8(+) T cells were isolated from the spleen. After human factor IX
      (hF.IX) gene transfer, anti-hF.IX antibodies were induced. These immune responses
      were not detected in mice injected with heat-inactivated or genome-lacking LVs or
      in GFP-transgenic mice, indicating that they were specifically triggered by
      transgene expression in vivo. Intriguingly, selective targeting of LV expression
      to hepatocytes limited the immune responses to the transgenes. By this approach,
      high levels of hF.IX, potentially in the therapeutic range, were reached and
      maintained long term in immunocompetent mice, without inducing antibody
      formation. These results prompt further studies in relevant animal models to
      explore the potential of in vivo LV administration for the gene therapy of
      hemophilias and other liver-based diseases.

PMID- 14701691
TI  - Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone
      marrow.
AB  - Plasma cells (PCs) represent the final stage of B-cell differentiation and are
      devoted to the production of immunoglobulin (Ig). Perturbations to their
      development can result in human disorders characterized by PC expansion and
      hypergammaglobulinemia. Ig-secreting cells (ISCs) have been identified in
      secondary lymphoid tissues and bone marrow (BM). Most ISCs in lymphoid tissue are
      short-lived; in contrast, ISCs that migrate to the BM become long-lived PCs and
      continue to secrete immunoglobulin for extended periods. However, a small
      population of long-lived PCs has been identified in rodent spleen, suggesting
      that PCs may persist in secondary lymphoid tissue and that the spleen, as well as
      the BM, plays an important role in maintaining long-term humoral immunity. For
      these reasons, we examined ISCs in human spleen and identified a population that
      appears analogous to long-lived rodent splenic PCs. Human splenic ISCs shared
      morphologic, cellular, molecular, and functional characteristics with long-lived
      PCs in BM, demonstrating their commitment to the PC lineage. Furthermore, the
      detection of highly mutated immunoglobulin V region genes in splenic ISCs
      suggested they are likely to be antigen-selected and to secrete high-affinity
      immunoglobulin. Thus, our results suggest that splenic ISCs have an important
      role in humoral immunity and may represent the affected cell type in some B-cell
      dyscrasias.

PMID- 14701701
TI  - Interleukin-10 gene promoter polymorphisms influence the clinical outcome of
      diffuse large B-cell lymphoma.
AB  - The aim of the study was to investigate whether interleukin-10 (IL-10) genetic
      polymorphisms influence this cytokine production as well as the incidence and
      outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10(-1082G)
      allele was found to be higher in 199 patients with DLBCL as compared with 112
      control subjects (0.47 versus 0.39, P =.043). Increased serum levels of IL-10
      were associated with adverse prognostic factors and poor DLBCL outcome. The
      frequencies of IL-10(-819T) and IL-10(-592A) alleles were lower in patients with
      elevated IL-10 serum levels (0.155 versus 0.32, P =.14). As compared with
      patients carrying the IL-10(-1082AA) genotype, patients with the IL-10(-1082G)
      allele (IL-10(-1082GG/GA) genotypes) had higher complete remission rate (78%
      [confidence interval (CI), 71%-85%] versus 65% [CI, 52%-78%], P =.07), 5-year
      freedom from progression (FFP) (60% [CI, 52%-68%] versus 40% [CI, 27%-53%], P
      =.013), and overall survival (OS) (63% [CI, 55%-71%] versus 33% [CI, 20%-45%], P
      =.0009). Among factors of the International Prognostic Index, IL-10(-1082G)
      allele remained an independent variable, predicting longer freedom from
      progression (FFP) (RR [relative risk] =.76, P =.00035) and OS (RR =.78, P
      =.0015). These results indicate that IL-10 production contributes to the clinical
      course of DLBCL and that this phenomenon involves a substantial genetic
      component.

PMID- 14701702
TI  - JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute
      promyelocytic leukemia cells.
AB  - Arsenic trioxide induces c-jun N-terminal kinase (JNK) activation and apoptosis
      in acute promyelocytic leukemia (APL), where it has major clinical activity, but
      whether JNK is necessary to induce apoptosis is unknown. To clarify this
      necessity, we established 2 arsenic trioxide (As(2)O(3))-resistant subclones of
      the APL cell line, NB4. Both resistant lines showed little activation of JNK1
      following treatment with As(2)O(3), even at doses sufficient to elicit robust
      activation in NB4 cells. One mechanism of resistance in these cells is up
      regulated glutathione (GSH) content, and GSH depletion by l-buthionine-[S,R]
      sulfoximine (BSO) restores JNK activation and As(2)O(3) sensitivity. This
      correlation between JNK activation and apoptosis led us to test whether
      inhibition of JNK would protect cells from As(2)O(3)-induced apoptosis. SEK1(-/-)
      mouse embryo fibroblasts (MEFs) showed diminished JNK activation following
      As(2)O(3) treatment and were protected from As(2)O(3)-induced but not doxorubicin
      induced apoptosis. Furthermore, treatment of arsenic trioxide-sensitive APL cells
      with the JNK inhibitor, dicumarol, significantly increased growth and survival in
      response to As(2)O(3) but did not protect cells from doxorubicin. Together, these
      data support an essential role for JNK signaling in the induction of growth
      inhibition and apoptosis by As(2)O(3) and suggest that activating JNK may provide
      a therapeutic advantage in the treatment of cancers that do not respond to
      arsenic alone.

PMID- 14701703
TI  - Essential role of HGF (hepatocyte growth factor) in blood formation in Xenopus.
AB  - In this study, we investigated the role of hepatocyte growth factor (HGF) in
      blood formation during Xenopus development. First, we examined the gene
      expression of HGF and its receptor, c-met, by whole-mount in situ hybridization
      during development. Strong signals of HGF as well as c-met were detected early in
      the developing ventral mesoderm, which later gives rise to the ventral blood
      island. Furthermore, to study the role of HGF, we blocked the HGF signaling
      pathway in Xenopus embryos by using truncated c-met lacking the tyrosine kinase
      domain. Injection of truncated c-met mRNA resulted in a marked decrease in the
      number of circulating blood cells. Similar results were obtained using morpholino
      antisense HGF oligonucleotides. Moreover, we also analyzed the expression of
      several early primitive blood markers in the blood island of these embryos. RNA
      in situ analysis revealed a significant reduction (or absence) of stem cell
      leukemia (SCL), alpha-globin, and GATA-1 expression, but not GATA-2 expression.
      In contrast, no significant difference was observed in the levels of expression
      of early definitive blood markers, SCL, GATA-2, and GATA-3 in the dorsolateral
      plate, as analyzed by in situ hybridization. Overall, the present study
      demonstrated that HGF is necessary for primitive hematopoiesis by regulating the
      expression of SCL.

PMID- 14701704
TI  - Interleukin-10 and tumor necrosis factor alpha region haplotypes predict
      transplant-related mortality after unrelated donor stem cell transplantation.
AB  - Certain cytokine gene polymorphisms have been shown to correlate with outcome of
      human leukocyte antigen (HLA) identical sibling donor stem cell transplantation
      (SCT), but in unrelated donor SCT such information is scarce. We have studied the
      association between cytokine gene polymorphism and transplant-related mortality
      (TRM) in 182 unrelated SCTs performed at a single center. We found association of
      polymorphism in the tumor necrosis factor alpha (TNF alpha) and interleukin-10
      (IL-10) gene and TRM. Both the TNFd4 allele and the TNF alpha -1031C alleles are
      associated with high risk for TRM. Statistical analysis showed that both
      polymorphisms were present on a single haplotype. This haplotype was associated
      with high risk of TRM when present in recipient or donor, 55% (43%-67%) compared
      with 21% (12%-30%) when absent from both (P <.01). A further allele associated
      with this haplotype, TNFa5, is also associated with increased risk of TRM. For IL
      10, presence of the donor R2-G-C-C haplotype was associated with decreased risk
      of TRM, 61% (43%-79%) versus 34% (25%-43%), P =.01. In contrast, possession of
      the R3-G-C-C haplotype by the donor predicted reduced risk of TRM, 30% (19%-41%,
      95% CI) versus 53% (40%-66%, 95% CI), P =.01. No independent associations of
      cytokine polymorphisms with acute graft-versus-host disease were shown.

PMID- 14701705
TI  - Fine particulate matter induces amphiregulin secretion by bronchial epithelial
      cells.
AB  - Particulate matter (PM) is thought to be responsible for respiratory health
      problems. Epithelial cells exposed to particles release pro-inflammatory
      cytokines leading to inflammation of airways. However, the signaling cascades
      triggered by particles are poorly understood. We demonstrate that PM with an
      aerodynamic diameter < 2.5 microm (PM2.5) or diesel exhaust particles upregulate
      the expression of amphiregulin (AR), a ligand of the epidermal growth factor
      receptor (EGFR), in human bronchial epithelial cells. AR secretion was blocked by
      an inhibitor of the EGFR tyrosine kinase (AG1478), or a selective mitogen
      activated protein (MAP) kinase/extracellular regulated kinase (Erk) inhibitor
      (PD98059), but not by the p38 MAP kinase inhibitor (SB203580). Thus, AR secretion
      is mediated through the activation of the EGFR and Erk MAP kinase pathway. In
      addition, AR secretion was inhibited by the antioxidant N-acetyl cysteine, but
      not by a neutralizing anti-EGFR, suggesting an EGFR transactivation via oxidative
      stress. AR may be involved in cytokine secretion, as AR can induce granulocyte
      macrophage-colony-stimulating factor (GM-CSF) release and a neutralizing anti
      EGFR reduces the particle-induced GM-CSF release. This study indicates that PM2.5
      induces the expression and secretion of AR, an EGFR ligand contributing to GM-CSF
      release, which may reflect an important mechanism for sustaining the
      proinflammatory response.

PMID- 14701706
TI  - Augmentation of endogenous dopamine production increases lung liquid clearance.
AB  - We have previously reported that dopamine increased active Na+ transport in rat
      lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether
      alveolar epithelial cells produce dopamine and whether increasing endogenous
      dopamine production by feeding rats a 4% tyrosine diet (TSD) would increase lung
      liquid clearance. Alveolar Type II cells express the enzyme aromatic-L-amino acid
      decarboxylase (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L
      tyrosine (L-dopa), produce dopamine. Rats fed TSD, a precursor of L-dopa and
      dopamine, had increased urinary dopamine levels, which were inhibited by
      benserazide, an inhibitor of AADC. Rats fed TSD for 15, 24, and 48 hours had a
      26, 46, and 45% increase in lung liquid clearance, respectively, as compared with
      controls. Also, dopaminergic D1 receptor antagonist--but not dopaminergic D2
      receptor antagonist--inhibited the TSD-mediated increase in lung liquid
      clearance. Alveolar Type II cells isolated from the lungs of rats after they had
      been fed TSD for 24 hours demonstrated increased protein abundance of Na,K-ATPase
      alpha1 and beta1 subunits. Basolateral membranes isolated from peripheral lung
      tissue of tyrosine-fed rats had increased Na,K-ATPase activity and Na,K-ATPase
      alpha1 subunit. These data provide the first evidence that alveolar epithelial
      cells produce dopamine and that increasing endogenous dopamine increases lung
      liquid clearance.

PMID- 14701707
TI  - Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in
      vivo and in vitro.
AB  - The incidence of hypersensitivity pneumonitis (HP) is lower in smokers than in
      nonsmokers. Because nicotine is immunosuppressive, we hypothesized that it could
      have a protective effect on HP induction in vivo. HP was induced in mice that
      were treated with nicotine either intraperitoneally (IP) (0.5 to 2.0 mg/kg/day)
      or intranasally (IN) (0.025 to 2.0 mg/kg/day). Both IP- and IN-treated animals
      had fewer bronchoalveolar lavage total cells and lymphocytes and a decreased lung
      tissue inflammation. IFN-gamma but not interleukin-10 mRNA expression was reduced
      in lung tissue of 2.0-mg/kg IN-treated animals. To test the effect of nicotine on
      alveolar macrophages, AMJ2-C11 cells were treated with nicotine and stimulated
      with lipopolysaccharide or Saccharopolyspora rectivirgula, a causative agent of
      HP. Nicotine reduced tumor necrosis factor release and tumor necrosis factor,
      interleukin-10, and IFN-gamma mRNA expression after stimulation and decreased
      CD80 expression by 55% in lipopolysaccharide-stimulated cells and by 41% in S.
      rectivirgula-stimulated cells. We conclude that nicotine could be, at least in
      part, responsible for the protection observed in smokers against HP. The
      inhibitory effect of nicotine on alveolar macrophages could be one of the
      mechanisms involved.

PMID- 14701708
TI  - Oxidative stress in severe pulmonary hypertension.
AB  - Severe pulmonary hypertension (PH) occurs in a primary or "unexplained" form and
      in a group of secondary forms associated with a number of diseases. Because the
      lung tissue from patients with severe PH demonstrates complex vascular lesions,
      which contain inflammatory cells, we wondered whether the lung tissue from
      patients with severe PH was "under oxidative stress." We used
      immunohistochemistry to localize nitrotyrosine and 8-hydroxy guanosine in the
      lung tissue sections from patients with primary and secondary PH. In some lung
      tissue extracts, the eicosanoid metabolites 5-oxo-eicosatetraenoic acid,
      leukotriene B4 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE were
      measured using mass spectroscopy, and superoxide dismutase amount and activity
      were measured. Nitrotyrosine expression was ubiquitous in all PH lungs, and 5-oxo
      eicosatetraenoic acid and HETE levels were elevated in the lungs of patients with
      severe PH but not in those lungs that were from the patients with severe PH
      treated chronically with prostacyclin. We conclude that indeed the lungs from
      patients with severe PH are under oxidative stress and that chronic prostacyclin
      infusion has an antiinflammatory effect on the lung tissue.

PMID- 14701709
TI  - Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway
      remodeling in mice.
AB  - The mechanisms underlying airway hyperresponsiveness remain unclear, although
      airway inflammation and remodeling likely play important roles. We have observed
      sustained airway hyperreactivity and airway remodeling occurring in mice after
      chronic allergen exposure and persisting beyond resolution of allergen-induced
      inflammation. The aim of this study was to delineate mechanisms involved in
      allergen-induced airway hyperreactivity and airway remodeling and to examine
      evidence for a causal association between airway remodeling and sustained airway
      hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13
      deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen
      exposure. By measuring airway responsiveness and airway morphometry, we
      demonstrated that WT mice developed sustained airway hyperreactivity and aspects
      of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/
      ) mice were protected from developing sustained airway hyperreactivity and
      aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained
      airway hyperreactivity and aspects of airway remodeling similar to that seen in
      WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for
      the development of sustained airway hyperreactivity and airway remodeling after
      allergen exposure.

PMID- 14701710
TI  - Patients with active tuberculosis often have different strains in the same sputum
      specimen.
AB  - It is generally accepted that tuberculosis results from a single infection with a
      single Mycobacterium tuberculosis strain. Such infections are thought to confer
      protective immunity against exogenous reinfection. In this study, a novel
      polymerase chain reaction method was developed to specifically identify M.
      tuberculosis strains belonging to the Beijing and non-Beijing evolutionary
      lineages in sputum specimens collected from tuberculosis patients resident in an
      epidemiologic field site in Cape Town, South Africa. The sensitivity and
      specificity of the polymerase chain reaction-based strain classification method
      were 100% (95% confidence interval, 85-100%) when compared with DNA
      fingerprinting and spacer oligotyping (spoligotyping). Application of this method
      showed that 19% of all patients were simultaneously infected with Beijing and non
      Beijing strains, and 57% of patients infected with a Beijing strain were also
      infected with a non-Beijing strain. Multiple infections were more frequent in
      retreatment cases (23%) as compared with new cases (17%), but were not associated
      with sex, age, or smear grading. These results suggest that multiple infections
      are frequent, implying high reinfection rates and the absence of efficient
      protective immunity conferred by the initial infection. This finding could
      influence our understanding of the epidemiology of disease in high-incidence
      regions and our understanding for vaccine development.

PMID- 14701711
TI  - Complement activation is critical to airway hyperresponsiveness after acute ozone
      exposure.
AB  - Ozone (O3) can induce airway hyperresponsiveness (AHR) and neutrophilic
      inflammation. We evaluated the role of complement in development of AHR and
      inflammation after acute O3 exposure in mice. Mice were exposed to O3 at 2 ppm
      for 3 hours, and airway responsiveness to methacholine was measured 8 hours after
      O3 exposure. Complement was depleted or inhibited by intraperitoneal injection of
      cobra venom factor (CVF) or complement receptor-related gene y (Crry)-Ig, a
      potent C3 convertase inhibitor; neutrophils were depleted using an antineutrophil
      monoclonal antibody. CVF attenuated the development of AHR by O3. Administration
      of Crry-Ig also prevented the development of AHR. Bronchoalveolar lavage (BAL)
      fluid neutrophilia after O3 exposure was significantly decreased by
      administration of either CVF or Crry-Ig. Increased BAL fluid total protein after
      O3 exposure was lowered by depletion or inhibition of complement. In contrast to
      the effects of complement inhibition or depletion, depletion of BAL neutrophil
      counts by more than 90% with the monoclonal antibody did not affect the
      development of AHR after O3 exposure. These data indicated that activation of the
      complement system follows acute O3 exposure and is important to the development
      of AHR and airway neutrophilia. However, this neutrophil response does not appear
      necessary for the development of AHR.

PMID- 14701712
TI  - Altered pulmonary vascular reactivity in mice with excessive erythrocytosis.
AB  - Pulmonary vascular remodeling during chronic hypoxia may be the result of either
      oxygen deprivation or erythrocytosis. To separate experimentally the effects of
      hypoxia and erythrocytosis, we analyzed transgenic mice that constitutively
      overexpress the human erythropoietin gene in an oxygen-independent manner. These
      mice are characterized by polycythemia but have normal blood pressure, heart
      rate, and cardiac output. In transgenic mice, pulmonary artery pressure (PAP) was
      increased in vivo but was reduced in blood-free perfused lungs. The thromboxane
      receptor agonist U46619 caused a smaller rise in PAP in isolated transgenic lungs
      than in lungs from wild-type mice. The transgenic pulmonary vasculature was
      characterized by elevated prostacyclin production, stronger endothelial nitric
      oxide synthase expression, and reduced pulmonary vascular smooth muscle
      thickness. The fact that transgenic polycythemic mice have marked pulmonary
      hypertension in vivo but not in vitro suggests that their pulmonary hypertension
      is due to the increased blood viscosity, thus supporting an independent role of
      polycythemia in the development of pulmonary hypertension. In addition, our
      findings indicate that the lungs of transgenic animals adapt to the high PAP by
      elevated synthesis of vasodilators and reduced vascular smooth muscle thickness
      that tend to reduce vascular tone and vascular responsiveness.

PMID- 14701713
TI  - The ethical relevance of the standard of care in the design of clinical trials.

PMID- 14701716
TI  - Bed rest attenuates sympathetic and pressor responses to isometric exercise in
      antigravity leg muscles in humans.
AB  - Although spaceflight and bed rest are known to cause muscular atrophy in the
      antigravity muscles of the legs, the changes in sympathetic and cardiovascular
      responses to exercises using the atrophied muscles remain unknown. We
      hypothesized that bed rest would augment sympathetic responses to isometric
      exercise using antigravity leg muscles in humans. Ten healthy male volunteers
      were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest,
      they performed isometric exercises using leg (plantar flexion) and forearm
      (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that
      continues to stimulate the muscle metaboreflex. These exercises were sustained to
      fatigue. We measured muscle sympathetic nerve activity (MSNA) in the
      contralateral resting leg by microneurography. In both pre- and post-bed-rest
      exercise tests, exercise intensities were set at 30 and 70% of the maximum
      voluntary force measured before bed rest. Bed rest attenuated the increase in
      MSNA in response to fatiguing plantar flexion by approximately 70% at both
      exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal
      voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter
      the increase in MSNA response to fatiguing handgrip and had no effects on the
      maximal voluntary force of handgrip. Although PEMI sustained MSNA activation
      before bed rest in all trials, bed rest entirely eliminated the PEMI-induced
      increase in MSNA in leg exercises but partially attenuated it in forearm
      exercises. These results do not support our hypothesis but indicate that bed rest
      causes a reduction in isometric exercise-induced sympathetic activation in
      (probably atrophied) antigravity leg muscles.

PMID- 14701717
TI  - Abdominal vagal mediation of the satiety effects of CCK in rats.
AB  - CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier
      permeability were used to test the hypothesis that satiety is mediated in part by
      CCK action at CCK1 receptors on vagal sensory nerves innervating the small
      intestine. Devazepide penetrates the blood-brain barrier; A-70104, the
      dicyclohexylammonium salt of N alpha-3-quinolinoyl-D-Glu-N,N-dipentylamide, does
      not. At dark onset, non-food-deprived control rats and rats with subdiaphragmatic
      vagotomies received a bolus injection of devazepide (2.5 micromol/kg i.v.) or a 3
      h infusion of A-70104 (3 micromol.kg(-1).h(-1) i.v.) either alone or
      coadministered with a 2-h intragastric infusion of peptone (0.75 or 1 g/h). Food
      intake was determined from continuous computer recordings of changes in food bowl
      weight. In control rats both antagonists stimulated food intake and attenuated
      the anorexic response to intragastric infusion of peptone. In contrast, only
      devazepide was effective in stimulating food intake in vagotomized rats. Thus
      endogenous CCK appears to act both at CCK1 receptors beyond the blood-brain
      barrier and by a CCK1 receptor-mediated mechanism involving abdominal vagal
      nerves to inhibit food intake.

PMID- 14701718
TI  - Tauroursodeoxycholate inhibits human cholangiocarcinoma growth via Ca2+-, PKC-,
      and MAPK-dependent pathways.
AB  - Tauroursodeoxychate (TUDCA) is used for the treatment of cholangiopathies
      including primary sclerosing cholangitis, which is considered the primary risk
      factor for cholangiocarcinoma. The effect of TUDCA on cholangiocarcinoma growth
      is unknown. We evaluated the role of TUDCA in the regulation of growth of the
      cholangiocarcinoma cell line Mz-ChA-1. TUDCA inhibited the growth of Mz-ChA-1
      cells in concentration- and time-dependent manners. TUDCA inhibition of
      cholangiocarcinoma growth was blocked by BAPTA-AM, an intracellular Ca(2+)
      concentration ([Ca(2+)](i)) chelator, and H7, a PKC-alpha inhibitor. TUDCA
      increased [Ca(2+)](i) and membrane translocation of the Ca(2+)-dependent PKC
      alpha in Mz-ChA-1 cells. TUDCA inhibited the activity of MAPK, and this
      inhibitory effect of TUDCA was abrogated by BAPTA-AM and H7. TUDCA did not alter
      the activity of Raf-1 and B-Raf and the phosphorylation of MAPK p38 and
      JNK/stress-activated protein kinase. TUDCA inhibits Mz-ChA-1 growth through a
      signal-transduction pathway involving MAPK p42/44 and PKC-alpha but independent
      from Raf proteins and MAPK p38 and JNK/stress-activated protein kinases. TUDCA
      may be important for the treatment of cholangiocarcinoma.

PMID- 14701719
TI  - Role of primary sensorimotor cortex and supplementary motor area in volitional
      swallowing: a movement-related cortical potential study.
AB  - We investigated the role of the cerebral cortex, particularly the face/tongue
      area of the primary sensorimotor (SMI) cortex (face/tongue) and supplementary
      motor area (SMA), in volitional swallowing by recording movement-related cortical
      potentials (MRCPs). MRCPs with swallowing and tongue protrusion were recorded
      from scalp electrodes in eight normal right-handed subjects and from implanted
      subdural electrodes in six epilepsy patients. The experiment by scalp EEG in
      normal subjects revealed that premovement Bereitschaftspotentials (BP) activity
      for swallowing was largest at the vertex and lateralized to either hemisphere in
      the central area. The experiment by epicortical EEG in patients confirmed that
      face/tongue SMI and SMA were commonly involved in swallowing and tongue
      protrusion with overlapping distribution and interindividual variability. BP
      amplitude showed no difference between swallowing and tongue movements, either at
      face/tongue SMI or at SMA, whereas postmovement potential (PMP) was significantly
      larger in tongue protrusion than in swallowing only at face/tongue SMI. BP
      occurred earlier in swallowing than in tongue protrusion. Comparison between
      face/tongue SMI and SMA did not show any difference with regard to BP and PMP
      amplitude or BP onset time in either task. The preparatory role of the cerebral
      cortex in swallowing was similar to that in tongue movement, except for earlier
      activation in swallowing. Postmovement processing of swallowing was lesser than
      that of tongue movement in face/tongue SMI; probably suggesting that the cerebral
      cortex does not play a significant role in postmovement processing of swallowing.
      SMA plays a supplementary role to face/tongue SMI both in swallowing and tongue
      movements.

PMID- 14701720
TI  - Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the
      absence of functional Mdr2, Abcg5, and Abcg8 transporters.
AB  - The ABC transporters bile salt export pump (BSEP; encoded by the ABCB11 gene),
      MDR3 P-glycoprotein (ABCB4), and sterolin 1 and 2 (ABCG5 and ABCG8) are crucial
      for the excretion of bile salt, phospholipid, and cholesterol, respectively, into
      the bile of mammals. The current paradigm is that phospholipid excretion mainly
      serves to protect membranes of the biliary tree against bile salt micelles. Bile
      salt composition and cytotoxicity, however, differ greatly between species. We
      investigated whether biliary phospholipid and cholesterol excretion occurs in a
      primitive species, the little skate, which almost exclusively excretes the
      sulphated bile alcohol scymnolsulphate. We observed no phospholipid and very
      little cholesterol excretion into bile of these animals. Conversely, when
      scymnolsulphate was added to the perfusate of isolated mouse liver perfusions, it
      was very well capable of driving biliary phospholipid and cholesterol excretion.
      Furthermore, in an erythrocyte cytolysis assay, scymnolsulphate was found to be
      at least as cytotoxic as taurocholate. These results demonstrate that the little
      skate does not have a system for the excretion of phospholipid and cholesterol
      and that both the MDR3 and the two half-transporter genes, ABCG5 and ABCG8, have
      evolved relatively late in evolution to mediate biliary lipid excretion. Little
      skate plasma membranes may be protected against bile salt micelles mainly by
      their high sphingomyelin content.

PMID- 14701721
TI  - Dual role of MEK/ERK signaling in senescence and transformation of intestinal
      epithelial cells.
AB  - The mitogen-activated protein kinase cascade operates downstream of Ras to convey
      cell-surface signals to the nucleus via nuclear translocation of ERK1 and ERK2.
      We and others have recently demonstrated that activation of ERK1/2 by growth
      factors is required for proliferation of intestinal epithelial crypt cells.
      However, it remained to be established whether ERK1/2 activation alone was
      sufficient to trigger intestinal epithelial cell (IEC) proliferation. To this
      aim, retrovirus encoding the hemagglutinin-tagged MAPK/ERK kinase (MEK)1 wild
      type (wtMEK), the upstream activator of ERK1/2, or a constitutively active mutant
      of MEK1 (MEK1-S218D/S222D; caMEK) were used to infect nonimmortalized human
      normal intestinal epithelial crypt cell cultures [human intestinal epithelial
      cells (HIEC)] and rodent immortalized intestinal crypt cells (IEC-6). Stable
      expression of caMEK but not wtMEK in HIEC led to the irreversible arrest of
      cellular proliferation (premature senescence). Concomitant with the onset of cell
      cycle arrest was the induction of the cyclin-dependent kinase inhibitors
      p21(Cip), p53, and p16(INK4A). By contrast, overexpression of caMEK in IEC-6
      cells induced growth factor relaxation for DNA synthesis, promoted morphological
      transformation and growth in soft agar, and did not affect expression of
      p21(Cip), p53, and p16(INK4A). We provided evidences that ERK1b, an alternatively
      spliced isoform of ERK1, is activated and may contribute to the deregulation of
      contact inhibition cell growth and transformation of these cells. Constitutive
      activation of MEK in IECs can produce either premature senescence or forced
      mitogenesis depending on the integrity of a senescence program controlled by the
      cell cycle inhibitors p53, p16(INK4A), and p21(CIP).

PMID- 14701722
TI  - Role of liver-enriched transcription factors and nuclear receptors in regulating
      the human, mouse, and rat NTCP gene.
AB  - Hepatic uptake of bile acids is mediated by the Na(+)-taurocholate cotransporting
      polypeptide (NTCP; SLC10A1) of the basolateral hepatocyte membrane. Several cis
      acting elements in the rat Ntcp gene promoter have been characterized. However,
      little is known about the mechanisms that control the expression of the human or
      mouse NTCP/Ntcp. We, therefore, compared the transcriptional regulation of the
      human and mouse NTCP/Ntcp gene with that of the rat. By computer alignment, a
      sequence in the 5'-regulatory region that is conserved between species was
      identified near the transcription start site. Huh7 cells were transfected with
      luciferase constructs containing the conserved region from each species. The
      hepatocyte nuclear factors (HNF)1alpha and -4alpha and the retinoid X
      receptor/retinoic acid receptor dimer (RXRalpha/RARalpha) bound and
      transactivated the rat but not the human or mouse NTCP/Ntcp promoters. In
      contrast, activation by the CCAAT/enhancer binding protein-beta was specific for
      human and mouse NTCP/Ntcp. The only consensus motif present in all three species
      was HNF3beta. HNF3beta formed a specific DNA-protein complex in electrophoretic
      mobility shift assays and inhibited NTCP/Ntcp promoter activity in cotransfection
      assays. Finally, a minor repressive effect of bile acids was only found for rat
      Ntcp. The transcriptional repressor small heterodimer partner (SHP) did not
      affect NTCP/Ntcp promoter activity. We conclude that 1) the transcriptional
      regulation of the conserved NTCP/Ntcp 5'-regulatory region differs considerably
      among human, mouse, and rat; and 2) the conserved NTCP/Ntcp regulatory region is
      not directly regulated by SHP. Bile acids may regulate NTCP/Ntcp indirectly by
      modulating the capacity of nuclear factors to activate gene expression.

PMID- 14701723
TI  - Distribution and function of the cannabinoid-1 receptor in the modulation of ion
      transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves.
AB  - We investigated the distribution and function of cannabinoid (CB)(1) receptors in
      the submucosal plexus of the guinea pig ileum. CB(1) receptors were found on both
      types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide
      Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively.
      CB(1) receptors colocalized with transient receptor potential vanilloid-1
      receptors on paravascular nerves and fibers in the submucosal plexus. In the
      submucosal ganglia, these nerves were preferentially localized at the periphery
      of the ganglia. In denervated ileal segments, CB(1) receptor immunoreactivity in
      submucosal neurons was not modified, but paravascular and intraganglionic fiber
      staining was absent. Short-circuit current (I(sc)) was measured as an indicator
      of net electrogenic ion transport in Ussing chambers. In the ion-transport
      studies, I(sc) responses to capsaicin, which activates extrinsic primary
      afferents, and to electrical field stimulation (EFS) were reduced by pretreatment
      with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were
      unaffected by VIP receptor desensitization, hexamethonium, alpha-amino-3-hydroxy
      5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor
      antagonists. The responses to capsaicin and EFS were reduced by 47 +/- 12 and 30
      +/- 14%, respectively, by the CB(1) receptor agonist WIN 55,212-2. This
      inhibitory effect was blocked by the CB(1) receptor antagonist, SR 141716A. I(sc)
      responses to forskolin or carbachol, which act directly on the epithelium, were
      not affected by WIN 55,212-2. The inhibitory effect of WIN 55,212-2 on EFS-evoked
      secretion was not observed in extrinsically denervated segments of ileum. Taken
      together, these data show cannabinoids act at CB(1) receptors on extrinsic
      primary afferent nerves, inhibiting the release of transmitters that act on
      cholinergic secretomotor pathways.

PMID- 14701724
TI  - DeltaNp73beta is active in transactivation and growth suppression.
AB  - p73, a p53 family protein, shares significant sequence homolog and functional
      similarity with p53. However, unlike p53, p73 has at least seven alternatively
      spliced isoforms with different carboxyl termini (p73alpha-eta). Moreover, the
      p73 gene can be transcribed from a cryptic promoter located in intron 3,
      producing seven more proteins (DeltaNp73alpha-eta). DeltaNp73, which does not
      contain the N-terminal activation domain in p73, has been thought to be
      transcriptionally inactive and dominant negative over p53 or p73. To systemically
      analyze the activity of the DeltaN variant, we generated stable cell lines, which
      inducibly express DeltaNp73alpha, DeltaNp73beta, and various DeltaNp73beta
      mutants by using the tetracycline-inducible expression system. Surprisingly, we
      found that DeltaNp73beta is indeed active in inducing cell cycle arrest and
      apoptosis. Importantly, we found that, when DeltaNp73beta is expressed at a
      physiologically relevant level, it is capable of suppressing cell growth. We then
      demonstrated that these DeltaNp73beta activities are not cell type specific. We
      showed that the 13 unique residues at the N terminus are required for
      DeltaNp73beta to suppress cell growth. We also found that, among the 13 residues,
      residues 6 to 10 are critical to DeltaNp73beta function. Furthermore, we found
      that DeltaNp73beta is capable of inducing some p53 target genes, albeit to a
      lesser extent than does p73beta. Finally, we found that the 13 unique residues,
      together with the N-terminal PXXP motifs, constitute a novel activation domain.
      Like DeltaNp73beta, DeltaNp73gamma is active in transactivation. However, unlike
      DeltaNp73beta, DeltaNp73alpha is inactive in suppressing cell growth. Our data,
      together with others' previous findings, suggest that DeltaNp73beta may have
      distinct functions under certain cellular circumstances.

PMID- 14701725
TI  - A permissive retinoid X receptor/thyroid hormone receptor heterodimer allows
      stimulation of prolactin gene transcription by thyroid hormone and 9-cis-retinoic
      acid.
AB  - Heterodimers of the retinoid X receptor (RXR) with the thyroid hormone receptor
      (TR) are considered to be nonpermissive. It is believed that within these
      complexes RXR acts as a "silent partner." We demonstrate here that a permissive
      heterodimer mediates stimulation of prolactin expression by the thyroid hormone
      T3 and by 9-cis retinoic acid (9-cis-RA). A response element located in the
      prolactin distal enhancer mediates transactivation by both ligands in pituitary
      cells, and RXR recruits coactivators when bound to this element as a heterodimer
      with TR. Furthermore, transcription by the RXR agonist can be obtained in CV-1
      cells only after overexpression of coactivators, and overexpression of
      corepressors inhibits the response in pituitary cells. Thus, cell type-specific
      differences in coregulator recruitment can determine the cellular response to
      both ligands. Coactivator recruitment by 9-cis-RA requires the ligand-dependent
      transactivation domains (AF-2) of both heterodimeric partners. Interestingly, the
      presence of the RXR ligand can overcome the deleterious effect of the AF-2
      mutation E401Q on association with coactivators and transactivation. These
      results demonstrate an unexpected role for RXR in TR signaling and show that in
      particular cellular environments this receptor can act as a "nonsilent" partner
      of TR, allowing stimulation by RXR agonists.

PMID- 14701726
TI  - Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase
      promoting complex/cyclosome-CDH1-mediated pathway.
AB  - The expression of human thymidine kinase 1 (hTK1) is highly dependent on the
      growth states and cell cycle stages in mammalian cells. The amount of hTK1 is
      significantly increased in the cells during progression to the S and M phases,
      and becomes barely detectable in the early G(1) phase by a proteolytic control
      during mitotic exit. This tight regulation is important for providing the correct
      pool of dTTP for DNA synthesis at the right time in the cell cycle. Here, we
      investigated the mechanism responsible for mitotic degradation of hTK1. We show
      that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and
      that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a
      necessary but also a rate-limiting factor for mitotic degradation of hTK1.
      Furthermore, a KEN box sequence located in the C-terminal region of hTK1 is
      required for its mitotic degradation and interaction capability with Cdh1. By in
      vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for
      degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif.
      Taken together, we concluded that activation of the APC/C-Cdh1 complex during
      mitotic exit controls timing of hTK1 destruction, thus effectively minimizing
      dTTP formation from the salvage pathway in the early G(1) phase of the cell cycle
      in mammalian cells.

PMID- 14701727
TI  - Slc25a13-knockout mice harbor metabolic deficits but fail to display hallmarks of
      adult-onset type II citrullinemia.
AB  - Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive disease
      caused by mutations in SLC25A13, the gene encoding the mitochondrial
      aspartate/glutamate carrier citrin. The absence of citrin leads to a liver
      specific, quantitative decrease of argininosuccinate synthetase (ASS), causing
      hyperammonemia and citrullinemia. To investigate the physiological role of citrin
      and the development of CTLN2, an Slc25a13-knockout (also known as Ctrn-deficient)
      mouse model was created. The resulting Ctrn-/- mice were devoid of Slc25a13 mRNA
      and citrin protein. Liver mitochondrial assays revealed markedly decreased
      activities in aspartate transport and the malate-aspartate shuttle. Liver
      perfusion also demonstrated deficits in ureogenesis from ammonia, gluconeogenesis
      from lactate, and an increase in the lactate-to-pyruvate ratio within
      hepatocytes. Surprisingly, Ctrn-/- mice up to 1 year of age failed to show CTLN2
      like symptoms due to normal hepatic ASS activity. Serological measures of
      glucose, amino acid, and ammonia metabolism also showed no significant
      alterations. Nitrogen-loading treatments produced only minor changes in the
      hepatic ammonia and amino acid levels. These results suggest that citrin
      deficiency alone may not be sufficient to produce a CTLN2-like phenotype in mice.
      These observations are compatible, however, with the variable age of onset,
      incomplete penetrance, and strong ethnic bias seen in CTLN2 where additional
      environmental and/or genetic triggers are now suspected.

PMID- 14701728
TI  - BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein
      WT1.
AB  - The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays
      a key role in the development of the kidneys. The transcriptional activation
      domain of WT1 is subject to regulation by a suppression region within the N
      terminus of WT1. Using a functional assay, we provide direct evidence that this
      requires a transcriptional cosuppressor, which we identify as brain acid soluble
      protein 1 (BASP1). WT1 and BASP1 associate within the nuclei of cells that
      naturally express both proteins. BASP1 can confer WT1 cosuppressor activity in
      transfection assays, and elimination of endogenous BASP1 expression augments
      transcriptional activation by WT1. BASP1 is present in the developing nephron
      structures of the embryonic kidney and, coincident with that of WT1, its
      expression is restricted to the highly specialized podocyte cells of the adult
      kidney. Taken together, our results show that BASP1 is a WT1-associated factor
      that can regulate WT1 transcriptional activity.

PMID- 14701729
TI  - Early glomerular filtration defect and severe renal disease in podocin-deficient
      mice.
AB  - Podocytes are specialized epithelial cells covering the basement membrane of the
      glomerulus in the kidney. The molecular mechanisms underlying the role of
      podocytes in glomerular filtration are still largely unknown. We generated
      podocin-deficient (Nphs2-/-) mice to investigate the function of podocin, a
      protein expressed at the insertion of the slit diaphragm in podocytes and
      defective in a subset of patients with steroid-resistant nephrotic syndrome and
      focal and segmental glomerulosclerosis. Nphs2-/- mice developed proteinuria
      during the antenatal period and died a few days after birth from renal failure
      caused by massive mesangial sclerosis. Electron microscopy revealed the extensive
      fusion of podocyte foot processes and the lack of a slit diaphragm in the
      remaining foot process junctions. Using real-time PCR and immunolabeling, we
      showed that the expression of other slit diaphragm components was modified in
      Nphs2-/- kidneys: the expression of the nephrin gene was downregulated, whereas
      that of the ZO1 and CD2AP genes appeared to be upregulated. Interestingly, the
      progression of the renal disease, as well as the presence or absence of renal
      vascular lesions, depends on the genetic background. Our data demonstrate the
      crucial role of podocin in the establishment of the glomerular filtration barrier
      and provide a suitable model for mapping and identifying modifier genes involved
      in glomerular diseases caused by podocyte injuries.

PMID- 14701730
TI  - Analysis of a mutant histone H3 that perturbs the association of Swi/Snf with
      chromatin.
AB  - We have isolated new histone H3 mutants in Saccharomyces cerevisiae that confer
      phenotypes indicative of transcriptional defects. Here we describe the
      characterization of one such mutant, encoded by the hht2-11 allele, which
      contains the single amino acid change L61W in the globular domain of H3. Whole
      genome expression analyses show that the hht2-11 mutation confers pleiotropic
      transcriptional defects and that many of the genes it affects are normally
      controlled by the Swi/Snf chromatin remodeling complex. Furthermore, we show that
      Swi/Snf occupancy at two promoters, PHO84 and SER3, is reduced in hht2-11
      mutants. Detailed studies of the PHO84 promoter suggest that the hht2-11 mutation
      impairs Swi/Snf association with chromatin in a direct fashion. Taken together,
      our results strongly suggest that the integrity of the globular domain of histone
      H3 is an important determinant in the ability of Swi/Snf to associate with
      chromatin.

PMID- 14701731
TI  - MKP-3 has essential roles as a negative regulator of the Ras/mitogen-activated
      protein kinase pathway during Drosophila development.
AB  - Mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) is a well-known
      negative regulator in the Ras/extracellular signal-regulated kinase (ERK)-MAPK
      signaling pathway responsible for cell fate determination and proliferation
      during development. However, the physiological roles of MKP-3 and the mechanism
      by which MKP-3 regulates Ras/Drosophila ERK (DERK) signaling in vivo have not
      been determined. Here, we demonstrated that Drosophila MKP-3 (DMKP-3) is
      critically involved in cell differentiation, proliferation, and gene expression
      by suppressing the Ras/DERK pathway, specifically binding to DERK via the N
      terminal ERK-binding domain of DMKP-3. Overexpression of DMKP-3 reduced the
      number of photoreceptor cells and inhibited wing vein differentiation.
      Conversely, DMKP-3 hypomorphic mutants exhibited extra photoreceptor cells and
      wing veins, and its null mutants showed striking phenotypes, such as embryonic
      lethality and severe defects in oogenesis. All of these phenotypes were highly
      similar to those of the gain-of-function mutants of DERK/rl. The functional
      interaction between DMKP-3 and the Ras/DERK pathway was further confirmed by
      genetic interactions between DMKP-3 loss-of-function mutants or overexpressing
      transgenic flies and various mutants of the Ras/DERK pathway. Collectively, these
      data provide the direct evidences that DMKP-3 is indispensable to the regulation
      of DERK signaling activity during Drosophila development.

PMID- 14701732
TI  - Direct association between mouse PERIOD and CKIepsilon is critical for a
      functioning circadian clock.
AB  - The mPER1 and mPER2 proteins have important roles in the circadian clock
      mechanism, whereas mPER3 is expendable. Here we examine the posttranslational
      regulation of mPER3 in vivo in mouse liver and compare it to the other mPER
      proteins to define the salient features required for clock function. Like mPER1
      and mPER2, mPER3 is phosphorylated, changes cellular location, and interacts with
      other clock proteins in a time-dependent manner. Consistent with behavioral data
      from mPer2/3 and mPer1/3 double-mutant mice, either mPER1 or mPER2 alone can
      sustain rhythmic posttranslational events. However, mPER3 is unable to sustain
      molecular rhythmicity in mPer1/2 double-mutant mice. Indeed, mPER3 is always
      cytoplasmic and is not phosphorylated in the livers of mPer1-deficient mice,
      suggesting that mPER3 is regulated by mPER1 at a posttranslational level. In
      vitro studies with chimeric proteins suggest that the inability of mPER3 to
      support circadian clock function results in part from lack of direct and stable
      interaction with casein kinase Iepsilon (CKIepsilon). We thus propose that the
      CKIepsilon-binding domain is critical not only for mPER phosphorylation but also
      for a functioning circadian clock.

PMID- 14701733
TI  - Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit.
AB  - In primary mammalian cells, DNA replication initiates in a small number of
      perinucleolar, lamin A/C-associated foci. During S-phase progression in
      proliferating cells, replication foci distribute to hundreds of sites throughout
      the nucleus. In contrast, we find that the limited perinucleolar replication
      sites persist throughout S phase as cells prepare to exit the cell cycle in
      response to contact inhibition, serum starvation, or replicative senescence.
      Proteins known to be involved in DNA synthesis, such as PCNA and DNA polymerase
      delta, are concentrated in perinucleolar foci throughout S phase under these
      conditions. Moreover, chromosomal loci are redirected toward the nucleolus and
      overlap with the perinucleolar replication foci in cells poised to undergo cell
      cycle exit. These same loci remain in the periphery of the nucleus during
      replication under highly proliferative conditions. These results suggest that
      mammalian cells undergo a large-scale reorganization of chromatin during the
      rounds of DNA replication that precede cell cycle exit.

PMID- 14701734
TI  - Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2
      competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin
      gene expression.
AB  - Sim2, a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought
      to be involved in some symptoms of Down's syndrome. In the course of searching
      for hypothetical Sim2 relatives, we isolated another bHLH-PAS factor, NXF. NXF
      was a novel gene and was selectively expressed in neuronal tissues. While no
      striking homolog of NXF was found in vertebrates, a Caenorhabditis elegans
      putative transcription factor, C15C8.2, showed similarity in the bHLH-PAS domain.
      NXF had an activation domain as a transcription activator, and Arnt-type bHLH-PAS
      subfamily members were identified as the heterodimer partners of NXF. The
      NXF/Arnt heterodimer was capable of binding and activating a subset of Sim2/Arnt
      target DNA variants, and Sim2 could compete with the NXF activity on the
      elements. We showed that Drebrin had several such NXF/Arnt binding elements on
      the promoter, which could be direct or indirect cross talking points between NXF
      (activation) and Sim2 (repression) action. Drebrin has been reported to be
      engaged in dendritic-cytoskeleton modulation at synapses, and such a novel NXF
      signaling system on neural gene promoter may be a molecular target of the adverse
      effects of Sim2 in the mental retardation of Down's syndrome.

PMID- 14701735
TI  - Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization.
AB  - MLL fusion proteins are oncogenic transcription factors that are associated with
      aggressive lymphoid and myeloid leukemias. We constructed an inducible MLL
      fusion, MLL-ENL-ERtm, that rendered the transcriptional and transforming
      properties of MLL-ENL strictly dependent on the presence of 4-hydroxy-tamoxifen.
      MLL-ENL-ERtm-immortalized hematopoietic cells required 4-hydroxy-tamoxifen for
      continuous growth and differentiated terminally upon tamoxifen withdrawal.
      Microarray analysis performed on these conditionally transformed cells revealed
      Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets
      upregulated by MLL-ENL-ERtm. Overexpression of the Hox repressor Bmi-1 inhibited
      the growth-transforming activity of MLL-ENL. Moreover, the enforced expression of
      Hoxa9 in combination with Meis1 was sufficient to substitute for MLL-ENL-ERtm
      function and to maintain a state of continuous proliferation and differentiation
      arrest. These results suggest that MLL fusion proteins impose a reversible block
      on myeloid differentiation through aberrant activation of a limited set of
      homeobox genes and Hox coregulators that are consistently expressed in MLL
      associated leukemias.

PMID- 14701736
TI  - MSH2-dependent germinal CTG repeat expansions are produced continuously in
      spermatogonia from DM1 transgenic mice.
AB  - Myotonic dystrophy type 1 is a neuromuscular affection associated with the
      expansion of an unstable CTG repeat in the DM protein kinase gene. The disease is
      characterized by somatic tissue-specific mosaicism and very high
      intergenerational instability with a strong bias towards expansions. We used
      transgenic mice carrying more than 300 unstable CTG repeats within their large
      human genomic environment to investigate the dynamics of CTG repeat germinal
      mosaicism in males. Germinal mosaicism towards expansions was already present in
      spermatozoa at 7 weeks of age and continued to increase with age, suggesting that
      expansions are continuously produced throughout life. To determine the precise
      stage at which germinal expansions occur during spermatogenesis, we sorted and
      collected the different germ cell types produced during spermatogenesis from
      males of different ages and analyzed the CTG repeat mosaicism in each fraction.
      Strong mosaicisms towards expansions were already observed in spermatogonia
      before meiosis. In transgenic Msh2-deficient mice, germinal instability of the
      CTG repeats (only contractions) also occurs premeiotically. No significant
      difference in mosaicism was detected between spermatogonia and spermatozoa,
      arguing against continued expansions during postmeiotic stages. This indicates
      that germinal expansions are produced at the beginning of spermatogenesis, in
      spermatogonia, by a meiosis-independent mechanism involving MSH2.

PMID- 14701737
TI  - EMILIN-1 deficiency induces elastogenesis and vascular cell defects.
AB  - EMILINs constitute a family of genes of the extracellular matrix with high
      structural similarity. Four genes have been identified so far in human and mouse.
      To gain insight into the function of this gene family, EMILIN-1 has been
      inactivated in the mouse by gene targeting. The homozygous animals were fertile
      and did not show obvious abnormalities. However, histological and ultrastructural
      examination revealed alterations of elastic fibers in aorta and skin. Formation
      of elastic fibers by mutant embryonic fibroblasts in culture was also abnormal.
      Additional alterations were observed in cell morphology and anchorage of
      endothelial and smooth muscle cells to elastic lamellae. Considering that EMILIN
      1 is adhesive for cells and that the protein binds to elastin and fibulin-5,
      EMILIN-1 may regulate elastogenesis and vascular cell maintenance by stabilizing
      molecular interactions between elastic fiber components and by endowing elastic
      fibers with specific cell adhesion properties.

PMID- 14701738
TI  - Phosphorylation of critical serine residues in Gem separates cytoskeletal
      reorganization from down-regulation of calcium channel activity.
AB  - Gem is a small GTP-binding protein that has a ras-like core and extended chains
      at each terminus. The primary structure of Gem and other RGK family members (Rad,
      Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem
      functional activity is regulated. Two functions for Gem have been demonstrated,
      including inhibition of voltage-gated calcium channel activity and inhibition of
      Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation
      and neurite retraction. These functions for Gem have been ascribed to its
      interaction with the calcium channel beta subunit and Rho kinase beta,
      respectively. We show here that these functions are separable and regulated by
      distinct structural modifications to Gem. Phosphorylation of serines 261 and 289,
      located in the C-terminal extension, is required for Gem-mediated cytoskeletal
      reorganization, while GTP and possibly calmodulin binding are required for
      calcium channel inhibition. In addition to regulating cytoskeletal
      reorganization, phosphorylation of serine 289 in conjunction with serine 23
      results in bidentate 14-3-3 binding, leading to increased Gem protein half-life.
      Evidence presented shows that phosphorylation of serine 261 is mediated via a
      cdc42/protein kinase Czeta-dependent pathway. These data demonstrate that
      phosphorylation of serines 261 and 289, outside the GTP-binding region of Gem,
      controls its inhibition of Rho kinase beta and associated changes in the
      cytoskeleton.

PMID- 14701739
TI  - Coordination of DNA damage responses via the Smc5/Smc6 complex.
AB  - The detection of DNA damage activates DNA repair pathways and checkpoints to
      allow time for repair. Ultimately, these responses must be coordinated to ensure
      that cell cycle progression is halted until repair is completed. Several
      multiprotein complexes containing members of the structural maintenance of
      chromosomes family of proteins have been described, including the condensin and
      cohesin complexes, that are critical for chromosomal organization. Here we show
      that the Smc5/Smc6 (Smc5/6) complex is required for a coordinated response to DNA
      damage and normal chromosome integrity. Fission yeast cells lacking functional
      Smc6 initiate a normal checkpoint response to DNA damage, culminating in the
      phosphorylation and activation of the Chk1 protein kinase. Despite this, cells
      enter a lethal mitosis, presumably without completion of DNA repair. Another
      subunit of the complex, Nse1, is a conserved member of this complex and is also
      required for this response. We propose that the failure to maintain a checkpoint
      response stems from the lack of ongoing DNA repair or from defective chromosomal
      organization, which is the signal to maintain a checkpoint arrest. The Smc5/6
      complex is fundamental to genome integrity and may function with the condensin
      and cohesin complexes in a coordinated manner.

PMID- 14701741
TI  - Impaired nipple development and parturition in LGR7 knockout mice.
AB  - LGR7 is a G-protein coupled receptor with structural homology to the
      gonadotrophin and thyrotrophin receptors. Recently, LGR7 was deorphanized, and it
      was shown that relaxin is the ligand for LGR7. To further study the function of
      this receptor, mice deficient for LGR7 were generated by replacing part of the
      transmembrane-encoding region with a LacZ reporter cassette. Here we show that
      LGR7 is expressed in various tissues, including the uterus, heart, brain, and
      testis. Fertility studies using female LGR7-/- mice showed normal fertility and
      litter size. However, some females were incapable of delivering their pups, and
      several pups were found dead. Moreover, all offspring died within 24 to 48 h
      after delivery because female LGR7-/- mice were unable to feed their offspring
      due to impaired nipple development. In some male LGR7-/- mice, spermatogenesis
      was impaired, leading to azoospermia and a reduction in fertility. Interestingly,
      these phenomena were absent in mutant mice at older ages or in later generations.
      Taken together, results from LGR7 knockout mice indicate an essential role for
      the LGR7 receptor in nipple development during pregnancy. Moreover, a defect in
      parturition was observed, suggesting a role for LGR7 in the process of cervical
      ripening.

PMID- 14701740
TI  - Phosphorylation of C/EBPalpha inhibits granulopoiesis.
AB  - CCAAT/enhancer-binding protein alpha (C/EBPalpha) is one of the key transcription
      factors that mediate lineage specification and differentiation of multipotent
      myeloid progenitors into mature granulocytes. Although C/EBPalpha is known to
      induce granulopoiesis while suppressing monocyte differentiation, it is unclear
      how C/EBPalpha regulates this cell fate choice at the mechanistic level. Here we
      report that inducers of monocyte differentiation inhibit the alternate cell fate
      choice, that of granulopoiesis, through inhibition of C/EBPalpha. This inhibition
      is mediated by extracellular signal-regulated kinases 1 and/or 2 (ERK1/2), which
      interact with C/EBPalpha through an FXFP docking site and phosphorylate serine
      21. As a consequence of C/EBPalpha phosphorylation, induction of granulocyte
      differentiation by C/EBPalpha or retinoic acid is inhibited. Our analysis of
      C/EBPalpha by fluorescent resonance energy transfer revealed that phosphorylation
      induces conformational changes in C/EBPalpha, increasing the distance between the
      amino termini of C/EBPalpha dimers. Thus, myeloid development is partly regulated
      by an ERK1/2-mediated change in the conformation of C/EBPalpha that favors
      monocyte differentiation by blocking granulopoiesis.

PMID- 14701742
TI  - Structural features of transcription factor IIIA bound to a nucleosome in
      solution.
AB  - Assembly of a DNA fragment containing a Xenopus borealis somatic-type 5S RNA gene
      into a nucleosome greatly restricts binding of the 5S gene-specific transcription
      factor IIIA (TFIIIA) to the 5S internal promoter. However, TFIIIA binds with high
      affinity to 5S nucleosomes lacking the N-terminal tail domains of the core
      histones or to nucleosomes in which these domains are hyperacetylated. The degree
      to which tail acetylation or removal improves TFIIIA binding cannot be simply
      explained by a commensurate change in the general accessibility of nucleosomal
      DNA. In order to investigate the molecular basis of how TFIIIA binds to the
      nucleosome and to ascertain if binding involves all nine zinc fingers and/or
      displacement of histone-DNA interactions, we examined the TFIIIA-nucleosome
      complex by hydroxyl radical footprinting and site-directed protein-DNA cross
      linking. Our data reveal that the first six fingers of TFIIIA bind and displace
      approximately 20 bp of histone-DNA interactions at the periphery of the
      nucleosome, while binding of fingers 7 to 9 appears to overlap with histone-DNA
      interactions. Molecular modeling based on these results and the crystal
      structures of a nucleosome core and a TFIIIA-DNA cocomplex yields a precise
      picture of the ternary complex and a potentially important intermediate in the
      transition from naive chromatin structure to productive polymerase III
      transcription complex.

PMID- 14701744
TI  - Immunological function in mice lacking the Rac-related GTPase RhoG.
AB  - RhoG is a low-molecular-weight GTPase highly expressed in lymphocytes that
      activates gene transcription and promotes cytoskeletal reorganization in vitro.
      To study the in vivo function of RhoG, we generated mice homozygous for a
      targeted disruption of the RhoG gene. Despite the absence of RhoG, the
      development of B and T lymphocytes was unaffected. However, there was an increase
      in the level of serum immunoglobulin G1 (IgG1) and IgG2b as well as a mild
      increase of the humoral immune response to thymus-dependent antigens. In
      addition, B- and T-cell proliferation in response to antigen receptor cross
      linking was slightly increased. Although RhoG deficiency produces a mild
      phenotype, our experiments suggest that RhoG may contribute to the negative
      regulation of immune responses. The lack of a strong phenotype could indicate a
      functional redundancy of RhoG with other Rac proteins in lymphocytes.

PMID- 14701743
TI  - Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair.
AB  - The pathway determining malignant cellular transformation, which depends upon
      mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body of
      evidence suggests that promotion of DNA double-strand break repair by homologous
      recombination (HR) may be the means by which BRCA1 maintains genomic stability,
      while a role of BRCA1 in error-prone nonhomologous recombination (NHR) processes
      has just begun to be elucidated. The BRCA1 protein becomes phosphorylated in
      response to DNA damage, but the effects of phosphorylation on recombinational
      repair are unknown. In this study, we tested the hypothesis that the BRCA1
      mediated regulation of recombination requires the Chk2- and ATM-dependent
      phosphorylation sites. We studied Rad51-dependent HR and random chromosomal
      integration of linearized plasmid DNA, a subtype of NHR, which we demonstrate to
      be dependent on the Mre11-Rad50-Nbs1 complex. Prevention of Chk2-mediated
      phosphorylation via mutation of the serine 988 residue of BRCA1 disrupted both
      the BRCA1-dependent promotion of HR and the suppression of NHR. Similar results
      were obtained when endogenous Chk2 kinase activity was inhibited by expression of
      a dominant-negative Chk2 mutant. Surprisingly, the opposing regulation of HR and
      NHR did not require the ATM phosphorylation sites on serines 1423 and 1524.
      Together, these data suggest a functional link between recombination control and
      breast cancer predisposition in carriers of Chk2 and BRCA1 germ line mutations.
      We propose a dual regulatory role for BRCA1 in maintaining genome integrity,
      whereby BRCA1 phosphorylation status controls the selectivity of repair events
      dictated by HR and error-prone NHR.

PMID- 14701745
TI  - Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent
      mechanism involving mitochondrial hexokinases.
AB  - The serine/threonine kinase Akt/protein kinase B inhibits apoptosis induced by a
      variety of stimuli, including overexpression or activation of proapoptotic Bcl-2
      family members. The precise mechanisms by which Akt prevents apoptosis are not
      completely understood, but Akt may function to maintain mitochondrial integrity,
      thereby preventing cytochrome c release following an apoptotic insult. This
      effect may be mediated, in part, via promotion of physical and functional
      interactions between mitochondria and hexokinases. Here we show that growth
      factor deprivation induced proteolytic cleavage of the proapoptotic Bcl-2 family
      member BID to yield its active truncated form, tBID. Activated Akt inhibited
      mitochondrial cytochrome c release and apoptosis following BID cleavage. Akt also
      antagonized tBID-mediated BAX activation and mitochondrial BAK oligomerization,
      two downstream events thought to be critical for tBID-induced apoptosis. Glucose
      deprivation, which impaired the ability of Akt to maintain mitochondrion
      hexokinase association, prevented Akt from inhibiting BID-mediated apoptosis.
      Interestingly, tBID independently elicited dissociation of hexokinases from
      mitochondria, an effect that was antagonized by activated Akt. Ectopic expression
      of the amino-terminal half of hexokinase II, which is catalytically active and
      contains the mitochondrion-binding domain, consistently antagonized tBID-induced
      apoptosis. These results suggest that Akt inhibits BID-mediated apoptosis
      downstream of BID cleavage via promotion of mitochondrial hexokinase association
      and antagonism of tBID-mediated BAX and BAK activation at the mitochondria.

PMID- 14701746
TI  - Molecular signatures of self-renewal, differentiation, and lineage choice in
      multipotential hemopoietic progenitor cells in vitro.
AB  - The molecular mechanisms governing self-renewal, differentiation, and lineage
      specification remain unknown. Transcriptional profiling is likely to provide
      insight into these processes but, as yet, has been confined to "static" molecular
      profiles of stem and progenitors cells. We now provide a comprehensive,
      statistically robust, and "dynamic" analysis of multipotent hemopoietic
      progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and
      multilineage differentiation in response to lineage-affiliated cytokines. Cells
      undergoing IL-3-dependent proliferative self-renewal displayed striking
      complexity, including expression of genes associated with different lineage
      programs, suggesting a highly responsive compartment poised to rapidly execute
      intrinsically or extrinsically initiated cell fate decisions. A remarkable
      general feature of early differentiation was a resolution of complexity through
      the downregulation of gene expression. Although effector genes characteristic of
      mature cells were upregulated late, coincident with morphological changes,
      lineage-specific changes in gene expression were observed prior to this,
      identifying genes which may provide early harbingers of unilineage commitment. Of
      particular interest were genes that displayed differential behavior irrespective
      of the lineage elaborated, many of which were rapidly downregulated within 4 to 8
      h after exposure to a differentiation cue. These are likely to include genes
      important in self-renewal, the maintenance of multipotentiality, or the negative
      regulation of differentiation per se.

PMID- 14701747
TI  - Eaf3 regulates the global pattern of histone acetylation in Saccharomyces
      cerevisiae.
AB  - Saccharomyces cerevisiae has a global pattern of histone acetylation in which
      histone H3 and H4 acetylation levels are lower at protein-coding sequences than
      at promoter regions. The loss of Eaf3, a subunit of the NuA4 histone acetylase
      and Rpd3 histone deacetylase complexes, greatly alters the genomic profile of
      histone acetylation, with the effects on H4 appearing to be more pronounced than
      those on H3. Specifically, the loss of Eaf3 causes increases in H3 and H4
      acetylation at coding sequences and decreases at promoters, such that histone
      acetylation levels become evenly distributed across the genome. Eaf3 does not
      affect the overall level of H4 acetylation, the recruitment of the NuA4 catalytic
      subunit Esa1 to target promoters, or the level of transcription of the genes
      analyzed for histone acetylation. Whole-genome transcriptional profiling
      indicates that Eaf3 plays a positive, but quantitatively modest, role in the
      transcription of a small subset of genes, whereas it has a negative effect on
      very few genes. We suggest that Eaf3 regulates the genomic profile of histone H3
      and H4 acetylation in a manner that does not involve targeted recruitment and is
      independent of transcriptional activity.

PMID- 14701748
TI  - Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent
      protein kinase A.
AB  - Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl
      groups from lysine residues of histone and nonhistone proteins. Recent studies
      suggest that they are key regulators of many cellular events, including cell
      proliferation and cancer development. Human class I HDACs possess homology to the
      yeast RPD3 protein and include HDAC1, HDAC2, HDAC3, and HDAC8. While HDAC1,
      HDAC2, and HDAC3 have been characterized extensively, almost nothing is known
      about HDAC8. Here we report that HDAC8 is phosphorylated by cyclic AMP-dependent
      protein kinase A (PKA) in vitro and in vivo. The PKA phosphoacceptor site of
      HDAC8 is Ser(39), a nonconserved residue among class I HDACs. Mutation of Ser(39)
      to Ala enhances the deacetylase activity of HDAC8. In contrast, mutation of
      Ser(39) to Glu or induction of HDAC8 phosphorylation by forskolin, a potent
      activator of adenyl cyclase, decreases HDAC8's enzymatic activity. Remarkably,
      inhibition of HDAC8 activity by hyperphosphorylation leads to hyperacetylation of
      histones H3 and H4, suggesting that PKA-mediated phosphorylation of HDAC8 plays a
      central role in the overall acetylation status of histones.

PMID- 14701749
TI  - The origin recognition complex and Sir4 protein recruit Sir1p to yeast silent
      chromatin through independent interactions requiring a common Sir1p domain.
AB  - Sir1p is one of four SIR (silent information regulator) proteins required for
      silencing the cryptic mating-type locus HMRa in the budding yeast Saccharomyces
      cerevisiae. A Sir1p interaction with Orc1p, the largest subunit of the origin
      recognition complex (ORC), is critical for Sir1p's ability to bind HMRa and
      function in the formation of silent chromatin. Here we show that a discrete
      domain within Sir1p, the ORC interaction region (OIR), was necessary and
      sufficient for a Sir1p-ORC interaction. The OIR contains the originally defined
      silencer recognition-defective region as well as additional amino acids. In
      addition, a Sir1p-Sir4p interaction required a larger region of Sir1p that
      included the OIR. Amino acid substitutions causing defects in either a Sir1p
      Orc1p or a Sir1p-Sir4p interaction reduced HMRa silencing and Sir1p binding to
      HMRa in chromatin. These data support a model in which Sir1p's association with
      HMRa is mediated by separable Sir1p-ORC and Sir1p-Sir4p interactions requiring a
      common Sir1p domain, and they indicate that a Sir1p-ORC interaction is restricted
      to silencers, at least in part, through interactions with Sir4p.

PMID- 14701750
TI  - Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD
      and dissociates negative effectors from the transactivation response element.
AB  - The elongation of transcription is a highly regulated process that requires
      negative and positive effectors. By binding the double-stranded stem in the
      transactivation response (TAR) element, RD protein from the negative
      transcription elongation factor (NELF) inhibits basal transcription from the long
      terminal repeat of the human immunodeficiency virus type 1 (HIVLTR). Tat and its
      cellular cofactor, the positive transcription elongation factor b (P-TEFb),
      overcome this negative effect. Cdk9 in P-TEFb also phosphorylates RD at sites
      next to its RNA recognition motif. A mutant RD protein that mimics its
      phosphorylated form no longer binds TAR nor represses HIV transcription. In sharp
      contrast, a mutant RD protein that cannot be phosphorylated by P-TEFb functions
      as a dominant-negative effector and inhibits Tat transactivation. These results
      better define the transition from abortive to productive transcription and thus
      replication of HIV.

PMID- 14701751
TI  - Targeted expression of the class II phosphoinositide 3-kinase in Drosophila
      melanogaster reveals lipid kinase-dependent effects on patterning and
      interactions with receptor signaling pathways.
AB  - Phosphoinositide 3-kinases (PI3Ks) can be divided into three distinct classes (I,
      II, and III) on the basis of their domain structures and the lipid signals that
      they generate. Functions have been assigned to the class I and class III enzymes
      but have not been established for the class II PI3Ks. We have obtained the first
      evidence for a biological function for a class II PI3K by expressing this enzyme
      during Drosophila melanogaster development and by using deficiencies that remove
      the endogenous gene. Wild-type and catalytically inactive PI3K_68D transgenes
      have opposite effects on the number of sensory bristles and on wing venation
      phenotypes induced by modified epidermal growth factor (EGF) receptor signaling.
      These results indicate that the endogenous PI3K_68D may act antagonistically to
      the EGF receptor-stimulated Ras-mitogen-activated protein kinase pathway and
      downstream of, or parallel to, the Notch receptor. A class II polyproline motif
      in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N
      terminal SH3 domain of Drk. Drk may thus be important for the localization of
      PI3K_68D, allowing it to modify signaling pathways downstream of cell surface
      receptors. The phenotypes obtained are markedly distinct from those generated by
      expression of the Drosophila class I PI3K, which affects growth but not pattern
      formation.

PMID- 14701752
TI  - Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by
      heterotypic and homotypic protein interactions.
AB  - Foxp1, Foxp2, and Foxp4 are large multidomain transcriptional regulators
      belonging to the family of winged-helix DNA binding proteins known as the Fox
      family. Foxp1 and Foxp2 have been shown to act as transcriptional repressors,
      while regulatory activity of the recently identified Foxp4 has not been
      determined. Given the importance of this Fox gene subfamily in neural and lung
      development, we sought to elucidate the mechanisms by which Foxp1, Foxp2, and
      Foxp4 repress gene transcription. We show that like Foxp1 and Foxp2, Foxp4
      represses transcription. Analysis of the N-terminal repression domain in Foxp1,
      Foxp2, and Foxp4 shows that this region contains two separate and distinct
      repression subdomains that are highly homologous termed subdomain 1 and subdomain
      2. However, subdomain 2 is not functional in Foxp4. Screening for proteins that
      interact with subdomains 1 and 2 of Foxp2 using yeast two-hybrid analysis
      revealed that subdomain 2 binds to C-terminal binding protein 1, which can
      synergistically repress transcription with Foxp1 and Foxp2, but not Foxp4.
      Subdomain 1 contains a highly conserved leucine zipper similar to that found in N
      myc and confers homo- and heterodimerization to the Foxp1/2/4 family members.
      These interactions are dependent on the conserved leucine zipper motif. Finally,
      we show that the integrity of this subdomain is essential for DNA binding, making
      Foxp1, Foxp2, and Foxp4 the first Fox proteins that require dimerization for DNA
      binding. These data reveal a complex regulatory mechanism underlying Foxp1,
      Foxp2, and Foxp4 activity, demonstrating that Foxp1, Foxp2, and Foxp4 are the
      first Fox proteins reported whose activity is regulated by homo- and
      heterodimerization.

PMID- 14701753
TI  - Distinct domains in the SHP-2 phosphatase differentially regulate epidermal
      growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) plays an important
      role in inflammation and cancer, is activated by a variety of stimuli including
      tumor necrosis factor alpha, interleukin-1, UV irradiation, and viruses, as well
      as receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR).
      Although previous studies suggest that EGFR can induce NF-kappaB, the mechanism
      of this activation remains unknown. In this study, we identify the components of
      the EGFR-induced signalosome in human glioblastoma cells required to regulate NF
      kappaB activation. Immunoprecipitation analyses with ErbB-modulated cells
      indicate that association between SHP-2 and Grb2-associated binder 1 (Gab1) is
      the critical step in the formation of the signalosome linking EGFR to NF-kappaB
      activation. We also show that EGFR-induced NF-kappaB activation is mediated by
      the PI3-kinase/Akt activation loop. Overexpression of SHP-2, Gab1, and
      myristoylated Akt significantly upregulated NF-kappaB transcriptional activity
      and DNA binding activity in glioblastoma cells. Interestingly, overexpression of
      either one of the two SH2 domain mutants of SHP-2, R32E or R138E, slightly
      reduced NF-kappaB activity relative to that of wild-type SHP-2, indicating that
      the SH2 domains of SHP-2 are required for EGFR-induced NF-kappaB activation. On
      the other hand, ectopic overexpression of either a Gab1 mutant incapable of
      binding to SHP-2 (Y627F) or a phosphatase-inactive SHP-2 mutant (C459S) caused a
      significant increase in NF-kappaB activity. Moreover, SHP-2 C459S-expressing
      cells displayed higher Gab1 phosphotyrosine content, suggesting that SHP-2
      regulates Gab1 phosphorylation through its phosphatase domain, which confers a
      negative regulatory effect on NF-kappaB activity. These results indicate that SHP
      2/Gab1 association is critical for linking EGFR to NF-kappaB transcriptional
      activity via the PI3-kinase/Akt signaling axis in glioblastoma cells and that SHP
      2 acts as a dual regulator of NF-kappaB activation.

PMID- 14701754
TI  - Telomere cap components influence the rate of senescence in telomerase-deficient
      yeast cells.
AB  - Cells lacking telomerase undergo senescence, a progressive reduction in cell
      division that involves a cell cycle delay and culminates in "crisis," a period
      when most cells become inviable. In telomerase-deficient Saccharomyces cerevisiae
      cells lacking components of the nonsense-mediated mRNA decay (NMD) pathway
      (Upf1,Upf2, or Upf3 proteins), senescence is delayed, with crisis occurring
      approximately 10 to 25 population doublings later than in Upf+ cells. Delayed
      senescence is seen in upfDelta cells lacking the telomerase holoenzyme components
      Est2p and TLC1 RNA, as well as in cells lacking the telomerase regulators Est1p
      and Est3p. The delay of senescence in upfDelta cells is not due to an increased
      rate of survivor formation. Rather, it is caused by alterations in the telomere
      cap, composed of Cdc13p, Stn1p, and Ten1p. In upfDelta mutants, STN1 and TEN1
      levels are increased. Increasing the levels of Stn1p and Ten1p in Upf+ cells is
      sufficient to delay senescence. In addition, cdc13-2 mutants exhibit delayed
      senescence rates similar to those of upfDelta cells. Thus, changes in the
      telomere cap structure are sufficient to affect the rate of senescence in the
      absence of telomerase. Furthermore, the NMD pathway affects the rate of
      senescence in telomerase-deficient cells by altering the stoichiometry of
      telomere cap components.

PMID- 14701755
TI  - Role of the C-terminal domain of RNA polymerase II in U2 snRNA transcription and
      3' processing.
AB  - U small nuclear RNAs (snRNAs) and mRNAs are both transcribed by RNA polymerase II
      (Pol II), but the snRNAs have unusual TATA-less promoters and are neither spliced
      nor polyadenylated; instead, 3' processing is directed by a highly conserved 3'
      end formation signal that requires initiation from an snRNA promoter. Here we
      show that the C-terminal domain (CTD) of Pol II is required for efficient U2
      snRNA transcription, as it is for mRNA transcription. However, CTD kinase
      inhibitors, such as 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and 1
      (5-isoquinolinesulfonyl)-2-methylpiperazine (H7), that block mRNA elongation do
      not affect U2 transcription, although 3' processing of the U2 primary transcript
      is impaired. We show further that U2 transcription is preferentially inhibited by
      low doses of UV irradiation or actinomycin D, which induce CTD kinase activity,
      and that UV inhibition can be rescued by treatment with DRB or H7. We propose
      that Pol II complexes transcribing snRNAs and mRNAs have distinct CTD
      phosphorylation patterns. mRNA promoters recruit factors including kinases that
      hyperphosphorylate the CTD, and the CTD in turn recruits proteins needed for mRNA
      splicing and polyadenylation. We predict that snRNA promoters recruit factors
      including a CTD kinase(s) whose snRNA-specific phosphorylation pattern recruits
      factors required for promoter-coupled 3' end formation.

PMID- 14701756
TI  - CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced
      transcription.
AB  - Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP)
      family ligands interact with specific membrane receptor complexes that have
      serine/threonine kinase activities. The receptor phosphorylation and activation
      induced by the ligands leads to phosphorylation of the Smad proteins, which
      translocate to the nucleus, controlling gene expression. Thus, regulation of Smad
      proteins is a key step in TGF-beta/BMP-induced signal transduction. Here we
      report a novel mechanism of the regulation of SMAD-mediated signaling, by which
      the Smad1 protein level is controlled through expression of the CHIP protein.
      CHIP is a U-box-dependent E3 ubiquitin ligase, previously identified as a
      cochaperon protein. However, we have isolated CHIP as a Smad-interacting protein
      in a yeast two-hybrid screen using Smad1 as bait. Furthermore we have shown CHIP
      Smad interaction using the (35)S-labeled CHIP protein, which can interact with
      glutathione S-transferase (GST)-Smad1 and GST-Smad4 in an in vitro protein
      binding assay. The CHIP-Smad interaction has been confirmed in vivo in mammalian
      cells through coimmunoprecipitation. Interestingly, we demonstrate that the
      coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation
      of the Smad proteins through a ubiquitin-mediated process. Consistent with the
      observation that CHIP induces Smad1 degradation, we further show that the
      expression of CHIP can inhibit the transcriptional activities of the Smad1/Smad4
      complex induced by BMP signals. Intriguingly, pBS/U6/CHIPi, which diminishes CHIP
      expression, significantly enhanced Smad1/Smad4- or BMPRIB(QD)-induced gene
      transcription. These results suggest that CHIP can interact with the Smad1/Smad4
      proteins and block BMP signal transduction through the ubiquitin-mediated
      degradation of Smad proteins.

PMID- 14701757
TI  - Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta
      secretase, by Sp1.
AB  - Proteolytic processing of the beta-amyloid precursor protein (APP) at the beta
      site is essential to generate Abeta. BACE1, the major beta-secretase involved in
      cleaving APP, has been identified as a type 1 membrane-associated aspartyl
      protease. We have cloned a 2.1-kb fragment upstream of the human BACE1 gene and
      identified key regions necessary for promoter activity. BACE1 gene expression is
      controlled by a TATA-less promoter. The region of bp -619 to +46 is the minimal
      promoter to control the transcription of the BACE1 gene. Several putative cis
      acting elements, such as a GC box, HSF-1, a PU box, AP1, AP2, and lymphokine
      response element, are found in the 5' flanking region of the BACE1 gene.
      Transcriptional activation and gel shift assays demonstrated that the BACE1
      promoter contains a functional Sp1 response element, and overexpression of the
      transcription factor Sp1 potentiates BACE gene expression and APP processing to
      generate Abeta. Furthermore, Sp1 knockout reduced BACE1 expression. These results
      suggest that BACE1 gene expression is tightly regulated at the transcriptional
      level and that the transcription factor Sp1 plays an important role in regulation
      of BACE1 to process APP generating Abeta in Alzheimer's disease.

PMID- 14701758
TI  - GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and
      2 activation by angiotensin II and epidermal growth factor.
AB  - Activation of the mitogen-activated protein kinase pathway represented by
      extracellular signal-regulated kinases (ERK1/2) and activation of the upstream
      kinase (MEK1) are critical events for growth factor signal transduction. c-Src
      has been proposed as a common mediator for these signals in response to both G
      protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs).
      Here we show that the GPCR kinase-interacting protein 1 (GIT1) is a substrate for
      c-Src that associates with MEK1 in vascular smooth-muscle cells and human
      embryonic kidney 293 cells. GIT1 binding via coiled-coil domains and a Spa2
      homology domain is required for sustained activation of MEK1-ERK1/2 after
      stimulation with angiotensin II and epidermal growth factor. We propose that GIT1
      serves as a scaffold protein to facilitate c-Src-dependent activation of MEK1
      ERK1/2 in response to both GPCRs and TKRs.

PMID- 14701759
TI  - Drosophila doubletime mutations which either shorten or lengthen the period of
      circadian rhythms decrease the protein kinase activity of casein kinase I.
AB  - In both mammals and fruit flies, casein kinase I has been shown to regulate the
      circadian phosphorylation of the period protein (PER). This phosphorylation
      regulates the timing of PER's nuclear accumulation and decline, and it is
      necessary for the generation of circadian rhythms. In Drosophila melanogaster,
      mutations affecting a casein kinase I (CKI) ortholog called doubletime (dbt) can
      produce short or long periods. The effects of both a short-period (dbt(S)) and
      long-period (dbt(L)) mutation on DBT expression and biochemistry were analyzed.
      Immunoblot analysis of DBT in fly heads showed that both the dbt(S) and dbt(L)
      mutants express DBT at constant levels throughout the day. Glutathione S
      transferase pull-down assays and coimmunoprecipitation of DBT and PER showed that
      wild-type DBT, DBT(S), and DBT(L) proteins can bind to PER equivalently and that
      these interactions are mediated by the evolutionarily conserved N-terminal part
      of DBT. However, both the dbt(S) and dbt(L) mutations reduced the CKI-7-sensitive
      kinase activity of an orthologous Xenopus laevis CKIdelta expressed in
      Escherichia coli. Moreover, expression of DBT in Drosophila S2 cells produced a
      CKI-7-sensitive kinase activity which was reduced by both the dbt(S) and dbt(L)
      mutations. Thus, lowered enzyme activity is associated with both short-period and
      long-period phenotypes.

PMID- 14701760
TI  - Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3
      deficient mice.
AB  - Heat shock proteins (HSPs) are highly conserved among all organisms from
      prokaryotes to eukaryotes. In mice, the HSP genes Hsp70.1 and Hsp70.3 are induced
      by both endogenous and exogenous stressors, such as heat and toxicants. In order
      to determine whether such proteins specifically influence genomic instability,
      mice deficient for Hsp70.1 and Hsp70.3 (Hsp70.1/3(-/-) mice) were generated by
      gene targeting. Mouse embryonic fibroblasts (MEFs) prepared from Hsp70.1/3(-/-)
      mice did not synthesize Hsp70.1 or Hsp70.3 after heat-induced stress. While the
      Hsp70.1/3(-/-) mutant mice were fertile, their cells displayed genomic
      instability that was enhanced by heat treatment. Cells from Hsp70.1/3(-/-) mice
      also display a higher frequency of chromosome end-to-end associations than do
      control Hsp70.1/3(+/+) cells. To determine whether observed genomic instability
      was related to defective chromosome repair, Hsp70.1/3(-/-) and Hsp70.1/3(+/+)
      fibroblasts were treated with ionizing radiation (IR) alone or heat and IR.
      Exposure to IR led to more residual chromosome aberrations, radioresistant DNA
      synthesis (a hallmark of genomic instability), increased cell killing, and
      enhanced IR-induced oncogenic transformation in Hsp70.1/3(-/-) cells. Heat
      treatment prior to IR exposure enhanced cell killing, S-phase-specific chromosome
      damage, and the frequency of transformants in Hsp70.1/3(-/-) cells in comparison
      to Hsp70.1/3(+/+) cells. Both in vivo and in vitro studies demonstrate for the
      first time that Hsp70.1 and Hsp70.3 have an essential role in maintaining genomic
      stability under stress conditions.

PMID- 14701761
TI  - Template requirements for telomerase translocation in Kluyveromyces lactis.
AB  - Telomeres are synthesized by telomerase, a specialized reverse transcriptase,
      which contains a template in its intrinsic RNA component. In Kluyveromyces
      lactis, the repeats synthesized by the wild-type telomerase are 25 nucleotides
      (nt) in length and uniform in sequence. To determine the role of the 5-nt repeats
      defining the ends of the K. lactis telomerase RNA template in telomerase
      translocation, we have made mutations in and around them and observed their
      effects on telomere length and the sequence of newly made telomeric repeats.
      These template mutations typically result in telomeres that are shorter than
      those of wild-type cells. The mismatches between the telomerase template and the
      telomeric tip that occur after telomerase-mediated incorporation of the mutations
      are normally not removed. Instead, the mutations lead to the synthesis of
      aberrant repeats that range in size from 31 to 13 bp. Therefore, the specificity
      with which the telomeric tip aligns with the telomere is critical for the
      production of the uniform repeats seen in K. lactis. In addition, the region
      immediately 3' of the template may play an important role in translocation of the
      enzyme.

PMID- 14701762
TI  - HOXA5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8.
AB  - HOXA5 is a transcriptional factor whose expression is lost in more than 60% of
      breast carcinomas. Our previous work demonstrated that the overexpression of
      HOXA5 in MCF7 cells resulted in cell death through a p53-dependent apoptotic
      pathway. To determine whether p53-independent apoptotic pathways are involved in
      HOXA5-induced cell death, we engineered a p53-mutant breast cancer cell line,
      Hs578T, to inducibly express HOXA5. Induction of HOXA5 expression led to cell
      death with features typical of apoptosis within 24 h, and the expression levels
      of mutant p53 and its target genes either decreased or remained unchanged. To
      decipher apoptotic pathways, the HOXA5-expressing cells were treated with a
      variety of apoptotic inhibitors. Besides a general caspase inhibitor, caspase 2-
      and 8-specific inhibitors largely abolished HOXA5-induced apoptosis, whereas
      caspase 1-, 3-, 6-, and 9-specific inhibitors had no significant effects. Western
      blot analysis further confirmed that caspases 2 and 8 were activated after the
      induction of HOXA5 expression. Further, several small interfering RNAs which
      specifically silenced caspase 2 and caspase 8 expression significantly blocked
      HOXA5-induced apoptosis. HOXA5 expression could also sensitize cells to tumor
      necrosis factor alpha-induced apoptosis by at least 100-fold. These results
      indicate that expression of HOXA5 can induce apoptosis through an apoptotic
      mechanism mediated by caspases 2 and 8.

PMID- 14701763
TI  - Human DNA polymerase iota utilizes different nucleotide incorporation mechanisms
      dependent upon the template base.
AB  - Human DNA polymerase iota (Poliota) is a member of the Y family of DNA
      polymerases involved in translesion DNA synthesis. Poliota is highly unusual in
      that it possesses a high fidelity on template A, but has an unprecedented low
      fidelity on template T, preferring to misincorporate a G instead of an A. To
      understand the mechanisms of nucleotide incorporation opposite different template
      bases by Poliota, we have carried out pre-steady-state kinetic analyses of
      nucleotide incorporation opposite templates A and T. These analyses have revealed
      that opposite template A, the correct nucleotide is preferred because it is bound
      tighter and is incorporated faster than the incorrect nucleotides. Opposite
      template T, however, the correct and incorrect nucleotides are incorporated at
      very similar rates, and interestingly, the greater efficiency of G
      misincorporation relative to A incorporation opposite T arises predominantly from
      the tighter binding of G. Based on these results, we propose that the incipient
      base pair is accommodated differently in the active site of Poliota dependent
      upon the template base and that when T is the templating base, Poliota
      accommodates the wobble base pair better than the Watson-Crick base pair.

PMID- 14701765
TI  - Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule
      combined with oxaliplatin as first-line treatment of metastatic colorectal
      cancer.
AB  - PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety
      of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and
      folinic acid (FA) as first-line treatment in metastatic colorectal cancer.
      PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85
      mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection
      with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60
      mg/m(2) every second week. The same doses of FU and FA were also given on day 2.
      RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or
      partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to
      72%). Nineteen patients showed stable disease, and 12 patients had progressive
      disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks
      later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median
      time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median
      overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to
      treat population. Neutropenia was the main adverse event, with grade 3 to 4
      toxicity in 58% of patients. Febrile neutropenia developed in seven patients.
      Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients
      and grade 2 in another 27 patients). CONCLUSION: Oxaliplatin combined with the
      bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and
      feasible bolus schedule as first-line treatment of metastatic colorectal cancer
      that yields comparable results compared with more complex schedules.

PMID- 14701766
TI  - Colon cancer screening practices after genetic counseling and testing for
      hereditary nonpolyposis colorectal cancer.
AB  - PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common
      hereditary form of colon cancer. Cancer screening recommendations differ between
      individuals identified to carry an HNPCC mutation and those who do not carry a
      known family mutation. We assessed the impact of genetic counseling and testing
      (GCT) on the use of endoscopic screening procedures and adherence to recommended
      endoscopic screening guidelines in 56 asymptomatic at-risk individuals from
      families known to carry an HNPCC mutation. PATIENTS AND METHODS: We analyzed data
      on colonoscopy and flexible sigmoidoscopy screenings collected before GCT and 6
      months and 12 months post-GCT on 17 mutation-positive and 39 true mutation
      negative individuals. Main outcome measures were use of endoscopic screening and
      adherence to recommended guidelines for the relevant mutation status. Mutation
      status, age, sex, employment, and income were analyzed as predictor variables.
      RESULTS: Among mutation-negative individuals, use of colonoscopy and flexible
      sigmoidoscopy decreased significantly between pre- and post-GCT (P <.00001 and P
      <.0003, respectively). Among mutation-positive individuals, a nonsignificant
      increase (P =.24) in use was noted. Age was also associated with use of
      endoscopic screening after GCT (P =.03). Mutation status (odds ratio [OR], 7.5; P
      =.02) and employment (OR, 8.6; P =.025) were associated with nonadherence to
      endoscopic screening guidelines. More mutation-negative individuals strictly
      adhered to guidelines than did mutation-positive individuals (87% v 65%).
      CONCLUSION: Genetic counseling and testing for HNPCC significantly influences the
      use of colonic endoscopy and adherence to recommendations for colon cancer
      screening.

PMID- 14701767
TI  - Phase I trial of combined-modality therapy for localized esophageal cancer:
      escalating doses of continuous-infusion paclitaxel with cisplatin and concurrent
      radiation therapy.
AB  - PURPOSE: To define the maximum-tolerated dose (MTD) of paclitaxel when given as a
      weekly 96-hour infusion with cisplatin and radiotherapy for patients with
      esophageal cancer. PATIENTS AND METHODS: Thirty-four patients with locally
      advanced esophageal cancer and three patients with local recurrence or positive
      resection margins were treated. Weekly paclitaxel doses of 10, 20, 30, 40, 60,
      and 80 mg/m(2), given as a continuous 96-hour infusion, were administered with
      weekly cisplatin, 30 mg/m(2) on day 1, weeks 1 to 6, and concurrent radiation
      (50.4 Gy). Plasma paclitaxel steady-state levels were measured. RESULTS: Dose
      limiting toxicity, defined as a treatment break longer than 2 weeks for toxicity,
      occurred in one patient in the 80-mg/m(2)/wk dose level. Major causes for any
      (including < or = 2 weeks) treatment breaks were mediport complications and
      neutropenic fever, which occurred mostly at that dose level. At a paclitaxel dose
      of 60 mg/m(2)/wk, myelosuppression, mostly neutropenia, was relatively mild and
      transient; stomatitis, esophagitis, diarrhea. and peripheral neuropathy were
      uncommon and usually of grade 2 or less. Therefore, the MTD was established at 60
      mg/m(2)/wk. The mean steady-state concentration of paclitaxel at the MTD was 17.2
      nmol/L. Complete (R0) resection was possible in 16 (73%) of 22 patients who
      underwent subsequent surgery, and the pathologic complete response rate was 24%.
      CONCLUSION: Weekly, 96-hour infusion of paclitaxel 60 mg/m(2)/wk, given with
      concurrent cisplatin and radiotherapy, is a safe and tolerable regimen for
      patients with localized esophageal cancer. Preliminary efficacy data are
      encouraging. This regimen is the basis of ongoing Radiation Therapy Oncology
      Group phase II randomized trials in esophageal and gastric cancers.

PMID- 14701768
TI  - Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor
      tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell
      cancer of the head and neck.
AB  - PURPOSE: To determine the efficacy and safety profiles of erlotinib in patients
      with advanced recurrent and/or metastatic squamous cell cancer of the head and
      neck (HNSCC). PATIENTS AND METHODS: Patients with locally recurrent and/or
      metastatic HNSCC, regardless of their HER1/EGFR status, were treated with
      erlotinib at an initial dose of 150 mg daily. Dose reductions or escalations were
      allowed based on tolerability of erlotinib. RESULTS: One-hundred fifteen patients
      were enrolled onto this study. Forty-seven percent of patients received erlotinib
      at 150 mg daily throughout the entire study, 6% had dose escalations, and 46%
      required dose reductions and/or interruptions. Five patients achieved partial
      responses on study, for an overall objective response rate of 4.3% (95% CI, 1.4%
      to 9.9%). Disease stabilization was maintained in 44 patients (38.3%) for a
      median duration of 16.1 weeks. The median progression-free survival was 9.6 weeks
      (95% CI, 8.1 to 12.1 weeks), and the median overall survival was 6.0 months (95%
      CI, 4.8 to 7.0 months). Subgroup analyses revealed a significant difference in
      overall survival favoring patients who developed at least grade 2 skin rashes
      versus those who did not (P =.045), whereas no difference was detected based on
      HER1/EGFR expression. Rash and diarrhea were the most common drug-related
      toxicities, encountered in 79% and 37% of patients, respectively, though the
      severity was mild to moderate in most cases. CONCLUSION: Erlotinib was well
      tolerated in this heavily pretreated HNSCC population and produced prolonged
      disease stabilization; hence, further evaluation of its role in this tumor type
      is warranted.

PMID- 14701769
TI  - The combination of p53 mutation and neu/erbB-2 amplification is associated with
      poor survival in node-negative breast cancer.
AB  - PURPOSE: Increases in neu/erbB-2 have been implicated in breast cancer prognosis,
      but do not predict all recurrences. On the basis of evidence that p53 mutation is
      involved in the development of human neoplasia, we examined the prognostic value
      of p53 alterations in combination with neu/erbB-2 amplification. PATIENTS AND
      METHODS: A consecutive series of women were observed for recurrence and death
      (median follow-up of 85 months) and tumors from 543 individuals were analyzed for
      p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53
      gene were analyzed by single-stranded conformational polymorphism and mutations
      were confirmed by DNA sequencing. The association of p53 mutation status and
      neu/erbB-2 amplification with risk of recurrence and death was examined in
      survival analyses with traditional and histologic markers as prognostic factors.
      RESULTS: p53 mutations occurred in 24.5% of the axillary node-negative breast
      carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2
      amplification: 38.9% compared with only 20.9% in those without neu/erbB-2
      amplification. We found elevated risks of disease recurrence and overall
      mortality in patients with both p53 mutation and neu/erbB-2 amplification in
      their tumor compared with patients with neither or only one of the alterations.
      This increase persisted with adjustment for other prognostic factors (relative
      risk, 2.32; P =.002 for recurrence; relative risk, 2.22; P =.004 for death).
      CONCLUSION: Evaluation of tumors for p53 mutations may be beneficial to identify
      women at higher risk of disease recurrence and death when the tumor has neu/erbB
      2 amplification, but in the absence of neu/erbB-2 amplification, the presence of
      p53 mutation may not provide additional independent prognostic information.

PMID- 14701770
TI  - Axillary treatment in conservative management of operable breast cancer:
      dissection or radiotherapy? Results of a randomized study with 15 years of follow
      up.
AB  - PURPOSE: Axillary dissection is the standard management of the axilla in invasive
      breast carcinoma. This surgery is responsible for functional sequelae and some
      options are considered, including axillary radiotherapy. In 1992, we published
      the initial results of a prospective randomized trial comparing lumpectomy plus
      axillary radiotherapy versus lumpectomy plus axillary dissection. We present an
      update of this study with a median follow-up of 180 months (range, 12 to 221
      months). PATIENTS AND METHODS: Between 1982 and 1987, 658 patients with a breast
      carcinoma less than 3 cm in diameter and clinically uninvolved lymph nodes were
      randomly assigned to axillary dissection or axillary radiotherapy. All patients
      underwent wide excision of the tumor and breast irradiation. RESULTS: The two
      groups were similar for age, tumor-node-metastasis system stage, and presence of
      hormonal receptors; 21% of the patients in the axillary dissection group were
      node-positive. Our initial results showed an increased survival rate in the
      axillary dissection group at 5 years (P =.009). At 10 and 15 years, however,
      survival rates were identical in both groups (73.8% v 75.5% at 15 years).
      Recurrences in the axillary node were less frequent in the axillary dissection
      group at 15 years (1% v 3%; P =.04). There was no difference in recurrence rates
      in the breast or supraclavicular and distant metastases between the two groups.
      CONCLUSION: In early breast cancers with clinically uninvolved lymph nodes, our
      findings show that long-term survival does not differ after axillary radiotherapy
      and axillary dissection. The only difference is a better axillary control in the
      group with axillary dissection.

PMID- 14701771
TI  - Menopausal status dependence of early mortality reduction due to diagnosis of
      smaller breast cancers (T1 v T2-T3): relevance to screening.
AB  - PURPOSE: To provide data relevant to the paradoxical mortality excess for women
      age 40 to 49 years observed during the first 6 to 8 years in the invited group in
      all mammography screening studies. PATIENTS AND METHODS: In 1,173 patients
      undergoing mastectomy alone as primary treatment, allocated to subsets according
      to menopausal status and tumor size, hazard rates for death were calculated. The
      ratios between the hazard rate for T2-T3 patients and the corresponding value for
      T1 patients were assessed over time. RESULTS: For postmenopausal patients, the
      ratio appeared to be time-dependent, dropping from the maximum value of
      approximately 5 at the first year after surgery to a near constant value of
      approximately 2 after 5 to 6 years. Premenopausal patients, on the contrary,
      showed a nearly constant ratio of approximately 3. Therefore, although in each T
      category the 10-year survival of premenopausal and postmenopausal patients was
      similar, its time distribution was menopause-dependent. In particular, the
      difference between cumulative survival of premenopausal and postmenopausal T2-T3
      patients attained statistical significance after 3 years. CONCLUSION: The
      mortality reduction due to the diagnosis of smaller tumors is significantly
      higher for postmenopausal women than for premenopausal women during early
      postsurgery time. According to the hypothesis that primary tumor surgical
      removal, occurring sooner in the invited group than in the control arm of
      screening trials, results in some acceleration of metastasis development, a
      greater number of unfavorable events (recurrence and death) should occur in the
      invited group. We suggest that for younger women, the early balance between
      benefit from tumor downsizing and harm from surgery-induced metastasis
      acceleration results in harm. This disadvantage does not occur in postmenopausal
      women.

PMID- 14701772
TI  - Combination chemotherapy with gemcitabine plus oxaliplatin in patients with
      intensively pretreated or refractory germ cell cancer: a study of the German
      Testicular Cancer Study Group.
AB  - PURPOSE: Long-term survival is rarely achieved in patients with cisplatin
      refractory germ cell cancer (GCT). Both single-agent gemcitabine and oxaliplatin
      have shown activity in patients who experience relapse or are refractory to
      cisplatin treatment. This study investigates the activity of a gemcitabine plus
      oxaliplatin regimen in these patients. PATIENTS AND METHODS: Gemcitabine was
      administered at a dose of 1,000 mg/m(2) on days 1 and 8; oxaliplatin was
      administered at a dose of 130 mg/m(2) on day 1. Response was evaluated every 4
      weeks. RESULTS: Thirty-five patients with a median age of 37 years (range, 21 to
      54 years) were enrolled onto the study. Primary tumor localization was gonadal,
      retroperitoneal, or mediastinal in 30, one, and four patients, respectively.
      Patients had been pretreated with a median of six platinum-containing cycles
      (range, four to 13 cycles) and 89% of patients previously had experienced
      treatment failure after high-dose chemotherapy with peripheral-blood stem-cell
      transplantation. Sixty-three percent of patients were considered absolutely
      cisplatin-refractory or cisplatin-refractory. A median of two cycles (range, 1 to
      6 cycles) per patient were applied. Toxicity consisted mainly of
      myelosuppression, with Common Toxicity Criteria grade 3 occurring in 54% of
      patients. Only 9% of patients developed neutropenic fever. Three patients
      attained a complete remission (CR), two patients attained a marker-negative
      partial remission, and 11 patients attained a marker-positive partial remission,
      resulting in an overall response rate of 46% (95% CI, 30% to 64%). All three
      patients with CR and one patient with a marker-negative partial remission
      remained disease free at 16+, 12+, 4+, and 2+ months of follow-up. Seven (44%) of
      these 16 responses, including one CR, occurred in cisplatin-refractory patients.
      CONCLUSION: Gemcitabine plus oxaliplatin demonstrates antitumor activity with
      acceptable toxicity in heavily pretreated patients with relapsed or cisplatin
      refractory GCT, and may offer a chance of long-term survival for selected
      patients.

PMID- 14701773
TI  - Phase II trial of PS-341 in patients with renal cell cancer: a University of
      Chicago phase II consortium study.
AB  - PURPOSE: Determine response rate, time to disease progression, and toxicity of
      the proteasome inhibitor PS-341 in patients with stage IV renal cell cancer.
      PATIENTS AND METHODS: PS-341 1.5 mg/m(2) was administered intravenously twice
      weekly for 2 weeks every 21 days. Dose escalation to 1.7 mg/m(2) ensued in the
      absence of grade 3 to 4 toxicities. Re-evaluation took place after three cycles.
      To assess proteasome inhibition, patients were randomly assigned to tumor core
      biopsy either before the first dose or after the third cycle of PS-341.
      Additionally, whole blood was collected at the same time intervals. RESULTS:
      Twenty-three patients were enrolled; 21 were assessable for response. Two
      patients were never treated (one patient refused treatment and one had
      insufficient tumor for biopsy). Eighteen patients completed at least three cycles
      of therapy; three patients experienced disease progression after two cycles.
      Grade 4 toxicities were arthralgia, diarrhea, and vomiting. Grade 3 toxicities
      included thrombocytopenia with one hemorrhage, anemia, febrile neutropenia,
      gastrointestinal toxicity, pain, fatigue, neuropathy (one sensory, one mixed
      sensorimotor), and electrolyte disturbances. Grade 1 to 2 neuropathy occurred in
      seven patients. One case of thrombosis and one case of pleural effusion occurred.
      Only one objective response was seen. Proteasome activity was measured by
      specific chymotryptic activity (SpA) and chymotryptic/tryptic activity (ChT:T).
      After PS-341, there was a decrease in mean whole blood SpA and ChT:T (P =.07
      and.11, respectively). CONCLUSION: Evidence is lacking for clinically significant
      activity of PS-341 in metastatic renal cell cancer. Insufficient biopsy and whole
      blood sample numbers preclude conclusions regarding proteasome inhibition within
      tumor. Further evaluation in this disease setting is not recommended.

PMID- 14701774
TI  - Biweekly 72-hour 9-aminocamptothecin infusion as second-line therapy for ovarian
      carcinoma: phase II study of the New York Gynecologic Oncology Group and the
      Eastern Cooperative Oncology Group.
AB  - PURPOSE: To determine the antitumor activity of the novel topoisomerase I
      inhibitor 9-aminocamptothecin (9-AC) given over 72 hours every 2 weeks in
      patients with ovarian carcinoma previously treated with one platinum-containing
      regimen. PATIENTS AND METHODS: Patients with ovarian carcinoma who received one
      prior platinum-containing regimen were eligible. Patients were stratified based
      on whether their disease was measurable, or nonmeasurable but assessable. 9-AC 35
      microg/m(2)/h was administered by continuous infusion for 72 hours every 2 weeks
      via ambulatory pump. RESULTS: Sixty patients were entered, 32 with measurable and
      28 with nonmeasurable but assessable disease. Ten (16.7%) of 60 patients
      responded (95% CI, 7.2% to 26.1%), with four complete responses and six partial
      remissions. The response rate for patients with measurable and nonmeasurable but
      assessable disease was 22% (95% CI, 7.6% to 36.2%) and 10.7% (95% CI, 2.3% to
      28.2%), respectively. None of the responders were platinum-resistant. Nineteen
      patients (32%) had stable disease. The major toxicities were hematologic, with
      25% of patients having grade 3 and 35% having grade 4 neutropenia, including five
      episodes of febrile neutropenia, 17% having grade 3 to 4 thrombocytopenia, and
      27% having grade 3 to 4 anemia. Nonhematologic toxicity included grade 3 to 4
      nausea (27%) and grade 3 to 4 vomiting (12%). CONCLUSION: This phase II
      multicenter trial of biweekly 72 hour 9-AC infusion as second-line therapy for
      ovarian cancer demonstrates comparable activity to standard approved agents in
      patients with both measurable and nonmeasurable but assessable disease. Toxicity
      consists mainly of moderate but controllable myelosuppression. Further studies
      combining 9-AC with other agents active in ovarian cancer for use as second-line
      therapy are warranted.

PMID- 14701776
TI  - Group II rhabdomyosarcoma and rhabdomyosarcomalike tumors: is radiotherapy
      necessary?
AB  - PURPOSE: In the prospective Cooperative Soft Tissue Sarcoma Study Group (CWS) 81,
      86, 91, and 96 trials, radiotherapy was omitted in some patients with
      rhabdomyosarcoma and rhabdomyosarcoma-like tumors within Intergroup
      Rhabdomyosarcoma Study (IRS) group II. This analysis evaluates whether subgroups
      can be defined for which radiotherapy is not necessary. PATIENTS AND METHODS: Two
      hundred three patients who were registered between January 1981 and December 1998
      were eligible for evaluation. Radiotherapy was given depending on tumor location,
      histology, and whether a secondary complete resection could be performed. The
      recommended radiation doses ranged from 32 to 54 Gy. RESULTS: One hundred ten
      patients did receive and 93 patients did not receive radiotherapy. The calculated
      local control after 5 years was 83% with and 65% without radiotherapy (P <.004).
      Event-free survival (EFS) at 5 years was 76% and 58%, respectively (P <.005).
      Overall survival (OS) at 5 years was 84% and 77% (P = not significant). The
      differences in local control were significant for the subgroups of irradiated
      patients with favorable histology, favorable site, and initial tumor size of less
      than 5 cm. A trend for improved local control with irradiation was observed for
      patients with unfavorable site, unfavorable histology, and large primary tumors.
      EFS was significantly improved for irradiated patients who had unfavorable
      histology, both favorable and unfavorable tumor sites, and small initial tumors.
      OS was significantly improved for patients with unfavorable histology through
      radiation. CONCLUSION: Local control and EFS in group II patients are improved
      with radiotherapy. No subgroup could be defined for which the omission of
      radiotherapy produced outcome equivalent to that of patients who were irradiated.

PMID- 14701775
TI  - Phase II trial of cisplatin/etoposide and concurrent radiotherapy followed by
      paclitaxel/carboplatin consolidation for limited small-cell lung cancer:
      Southwest Oncology Group 9713.
AB  - PURPOSE: Limited small-cell lung cancer (LSCLC) is characterized by a high
      initial response rate to chemoradiotherapy, but local or systemic relapse occurs
      in the majority of patients. Previous Southwest Oncology Group trials in LSCLC
      have utilized cisplatin and etoposide (PE) delivered concurrently with thoracic
      radiotherapy followed by two consolidation cycles. Newer chemotherapy regimens
      such as paclitaxel and carboplatin are active in small-cell lung cancer and hold
      the promise of improving both local and systemic control. S9713 evaluated the
      substitution of paclitaxel and carboplatin for PE consolidation in LSCLC.
      PATIENTS AND METHODS: Between July 1998 and August 1999, 96 patients were accrued
      from 43 institutions. Eighty-nine patients were eligible; 87 were assessable for
      survival and response. Treatment consisted of cisplatin 50 mg/m(2) on days 1, 8,
      29, and 36, and etoposide 50 mg/m(2) on days 1 to 5 and days 29 to 33, with
      concurrent radiotherapy of 61 Gy beginning on day 1. Consolidation therapy was
      carboplatin (area under the curve = 6) and paclitaxel 200 mg/m(2), both drugs
      administered on day 1 of a 21 day cycle for three cycles. RESULTS: The response
      rate was 86% (complete response, 33%; partial response, 53%). Median overall
      survival was 17 months (95% CI, 12.7 to 19.0). One- and 2-year overall survivals
      were 61% and 33%, respectively. Median progression-free survival (PFS) was 9
      months, 1-year PFS was 40%, and 2-year PFS was 21%. CONCLUSION: Consolidation
      therapy with paclitaxel and carboplatin in LSCLC resulted in an outcome similar
      to that seen in prior Southwest Oncology Group trials. This study and others
      which have tested paclitaxel in small-cell lung cancer dampens enthusiasm for
      this agent in the primary management of LSCLC.

PMID- 14701777
TI  - Pilot study of idarubicin-based intensive-timing induction therapy for children
      with previously untreated acute myeloid leukemia: Children's Cancer Group Study
      2941.
AB  - PURPOSE: Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show
      that in adults with acute myeloid leukemia (AML), IDA achieves higher remission
      rates and longer remission durations. In Children's Cancer Group Pilot Study CCG
      2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg
      of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in
      CCG-2891. PATIENTS AND METHODS: On days 1 through 3 and 10 through 14, patients
      received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and
      IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of
      IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients.
      Outcomes were compared with those of intensive timing in CCG-2891. RESULTS:
      Treatment-related mortality after two courses of induction was not significantly
      different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9%
      with DNR/DNR. In course 1 of CCG-2941 IDA/IDA, 11% of patients withdrew compared
      with 1.5% in CCG-2891 (P <.001) and 5% in CCG-2941 IDA/DNR (P = not significant).
      Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v
      36 days; P =.007), mean duration of course 1 by a week (P =.002), and risk of
      grade 3 or 4 hyperbilirubinemia (18% v 5%; P =.02). Toxicity of IDA/DNR was not
      different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast
      percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P =.004). Remission
      induction, survival, and event-free survival rates were not significantly
      different from those of CCG-2891. CONCLUSION: In CCG-2941, excessive toxicity and
      withdrawals outweighed potential benefits of early response with IDA.

PMID- 14701778
TI  - Neurocognitive function and progression in patients with brain metastases treated
      with whole-brain radiation and motexafin gadolinium: results of a randomized
      phase III trial.
AB  - PURPOSE: To report the neurocognitive findings in a phase III randomized trial
      evaluating survival and neurologic and neurocognitive function in patients with
      brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT)
      with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were
      randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5
      mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine
      motor skill was performed. RESULTS: Four hundred one patients were enrolled (251
      with non-small-cell lung cancer, 75 with breast cancer, and 75 with other
      cancers); 90.5% patients had impairment of one or more neurocognitive tests at
      baseline. Neurocognitive test scores of memory, fine motor speed, executive
      function, and global neurocognitive impairment at baseline were correlated with
      brain tumor volume and predictive of survival. There was no statistically
      significant difference between treatment arms in time to neurocognitive
      progression. Patients with lung cancer (but not other types of cancer) who were
      treated with MGd tended to have improved memory and executive function (P =.062)
      and improved neurologic function as assessed by a blinded events review committee
      (P =.048). CONCLUSION: Neurocognitive tests are a relatively sensitive measure of
      brain functioning; a combination of tumor prognostic variables and brain function
      assessments seems to predict survival better than tumor variables alone. Although
      the addition of MGd to WBRT did not produce a significant overall improvement
      between treatment arms, MGd may improve memory and executive function and prolong
      time to neurocognitive and neurologic progression in patients with brain
      metastases from lung cancer.

PMID- 14701779
TI  - Impact of hospital procedure volume on surgical operation and long-term outcomes
      in high-risk curatively resected rectal cancer: findings from the Intergroup 0114
      Study.
AB  - PURPOSE: Prior studies have demonstrated superior outcomes after a curative
      surgical resection of rectal cancer at hospitals where the volume of such
      surgeries is high. However, because these studies often lack detailed information
      on tumor and treatment characteristics as well as cancer recurrence, the true
      nature of this relation remains uncertain. PATIENTS AND METHODS: We studied a
      nested cohort of 1,330 patients with stage II and stage III rectal cancer
      participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed
      differences in rates of sphincter-preserving operations, overall survival, and
      cancer recurrence by hospital surgical volume. RESULTS: We observed a significant
      difference in the rates of abdominoperineal resections across tertiles of
      hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at
      medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after
      adjustment for tumor distance from the anal verge. However, this higher rate of
      sphincter-sparing operations at high-volume centers was not accompanied by any
      increase in recurrence rates. Hospital surgical volume did not predict overall,
      disease-free, recurrence-free, or local recurrence-free survival. However, among
      patients who did not complete the planned adjuvant chemoradiotherapy (270
      patients), those who underwent surgery at low-volume hospitals had a significant
      increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% CI, 1.01 to 3.72;
      P =.04 for the trend) and a nonsignificant trend toward increased overall
      mortality (P =.08) and local recurrence (P =.10). In contrast, no significant
      volume-outcome relation was noted among patients who did complete postoperative
      therapy. CONCLUSION: Using prospectively recorded data, we found that hospital
      surgical volume had no significant effect on rectal cancer recurrence or survival
      when patients completed standard adjuvant therapy. Sphincter-preserving surgery
      was more commonly performed at high-volume centers.

PMID- 14701780
TI  - Phase I study of the humanized antiepidermal growth factor receptor monoclonal
      antibody EMD72000 in patients with advanced solid tumors that express the
      epidermal growth factor receptor.
AB  - PURPOSE: To investigate the safety and tolerability and to explore the
      pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth
      factor receptor monoclonal antibody EMD72000 in patients with solid tumors that
      express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a
      phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR
      positive, solid malignancies that were not amenable to any established
      chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without
      routine premedication until disease progression or unacceptable toxicity.
      RESULTS: Twenty-two patients were treated with EMD72000 at five different dose
      levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria
      grade 3 headache and fever occurring after the first infusion were dose limiting
      at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe
      side effects, especially no allergic reactions or diarrhea, were observed.
      Acneiform skin reaction was the most common toxicity, but it was mild, with grade
      1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic
      analyses demonstrated a predictable pharmacokinetic profile for EMD72000.
      Pharmacodynamic studies on serial skin biopsies revealed that EMD72000
      effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation
      of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR
      protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization
      (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding
      patients received treatment for up to 18 months without cumulative toxicity.
      CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of
      activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at
      the investigated doses significantly inhibited downstream EGFR-dependent
      processes.

PMID- 14701781
TI  - Methadone versus morphine as a first-line strong opioid for cancer pain: a
      randomized, double-blind study.
AB  - PURPOSE: To compare the effectiveness and side effects of methadone and morphine
      as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS:
      Patients in international palliative care clinics with pain requiring initiation
      of strong opioids were randomly assigned to receive methadone (7.5 mg orally
      every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained
      release every 12 hours and 5 mg every 4 hours as needed). The study duration was
      4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49
      in the methadone group and 54 in the morphine group). The groups had similar
      baseline scores for pain, sedation, nausea, confusion, and constipation. Patients
      receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those
      receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at
      days 14 and 28 was similar between the two groups. More than three fourths of
      patients in each group reported a 20% or more reduction in pain intensity by day
      8. The proportion of patients with a 20% or more improvement in pain at 4 weeks
      in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the
      morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global
      benefit were nearly identical to the pain response rates and did not differ
      between the treatment groups. CONCLUSION: Methadone did not produce superior
      analgesic efficiency or overall tolerability at 4 weeks compared with morphine as
      a first-line strong opioid for the treatment of cancer pain.

PMID- 14701782
TI  - Uncommon presentations of Hodgkin's disease. Case 1. Hodgkin's disease of the
      jejunum.

PMID- 14701783
TI  - Uncommon presentations of Hodgkin's disease. Case 2. Hodgkin's disease of the
      nasopharynx.

PMID- 14701784
TI  - Uncommon presentations of Hodgkin's disease. Case 3. Hodgkin's disease: rectal
      presentation.

PMID- 14701785
TI  - Doctor, does this mean I'm going to starve to death?

PMID- 14701786
TI  - Peritoneal carcinomatosis: what can we do about it?

PMID- 14701788
TI  - Problems with nomenclature and pharmacodynamics in trophoblastic disease.

PMID- 14701790
TI  - Fluoxetine versus placebo in advanced cancer outpatients.

PMID- 14701791
TI  - Prescribing antidepressants to advanced cancer patients with mild depressive
      symptoms is not justified.

PMID- 14701795
TI  - Pleckstrin homology domain-mediated activation of the rho-specific guanine
      nucleotide exchange factor Dbs by Rac1.
AB  - Dbs is a Rho-specific guanine nucleotide exchange factor that was identified in a
      screen for proteins whose expression causes deregulated growth in NIH 3T3 mouse
      fibroblasts. Although Rac1 has not been shown to be a substrate for Dbs in either
      in vitro or in vivo assays, the Rat ortholog of Dbs (Ost) has been shown to bind
      specifically to GTP.Rac1 in vitro. The dependence of the Rac1/Dbs interaction on
      GTP suggests that Dbs may in fact be an effector for Rac1. Here we show that the
      interaction between activated Rac1 and Dbs can be recapitulated in mammalian
      cells and that the Rac1 docking site resides within the pleckstrin homology
      domain of Dbs. This interaction is specific for Rac1 and is not observed between
      Rac1 and several other members of the Rho-specific guanine nucleotide exchange
      factor family. Co-expression of Dbs with activated Rac1 causes enhanced focus
      forming activity and elevated levels of GTP.RhoA in NIH 3T3 cells, indicating
      that Dbs is activated by the interaction. Consistent with this, activated Rac1 co
      localizes with Dbs in NIH 3T3 cells, and natively expressed Rac1 relocalizes in
      response to Dbs expression. To summarize, we have characterized a surprisingly
      direct pleckstrin homology domain-mediated mechanism through which Rho GTPases
      can become functionally linked.

PMID- 14701796
TI  - The Rap GTPases regulate integrin-mediated adhesion, cell spreading, actin
      polymerization, and Pyk2 tyrosine phosphorylation in B lymphocytes.
AB  - Integrin-mediated adhesion plays an important role in B cell development and
      activation. Signaling initiated by antigens, chemokines, or phorbol esters can
      rapidly convert integrins to an activated adhesion-competent state. The binding
      of integrins to their ligands can then induce actin-dependent cell spreading,
      which can facilitate cell-cell adhesion or cell migration on extracellular
      matrices. The signaling pathways involved in integrin activation and post
      adhesion events in B cells are not completely understood. We have previously
      shown that anti-Ig antibodies, the chemokine stromal cell-derived factor-1 (SDF
      1; CXCL12), and phorbol esters activate the Rap1 and Rap2 GTPases in B cells and
      that Rap activation is essential for SDF-1-induced B cell migration (McLeod, S.
      J., Li, A. H. Y., Lee, R. L., Burgess, A. E., and Gold, M. R. (2002) J. Immunol.
      169, 1365-1371; Christian, S. L., Lee, R. L., McLeod, S. J., Burgess, A. E., Li,
      A. H. Y., Dang-Lawson, M., Lin, K. B. L., and Gold, M. R. (2003) J. Biol. Chem.
      278, 41756-41767). We show here that preventing Rap activation by expressing Rap
      specific GTPase-activating protein II (RapGAPII) significantly decreased
      lymphocyte function-associated antigen-1- and alpha(4) integrin-dependent binding
      of murine B cell lines to purified adhesion molecules and to other cells.
      Conversely, augmenting Rap activation by expressing a constitutively active form
      of Rap2 enhanced B cell adhesion, showing for the first time that Rap2 can
      promote integrin activation. We also show that blocking Rap activation inhibited
      anti-Ig-induced cell spreading and phorbol ester-induced actin polymerization as
      well as anti-Ig- and SDF-1-induced phosphorylation of Pyk2, a tyrosine kinase
      involved in morphological changes and chemokine-induced B cell migration. Thus,
      the Rap GTPases regulate integrin-mediated B cell adhesion as well as processes
      that control B cell morphology and migration.

PMID- 14701797
TI  - The C-terminal nonapeptide of mature chemerin activates the chemerin receptor
      with low nanomolar potency.
AB  - Chemerin is a novel protein identified as the natural ligand of ChemR23
      (chemerinR), a previously orphan G protein-coupled receptor expressed in immature
      dendritic cells and macrophages. Chemerin is synthesized as a secreted precursor,
      prochemerin, which is poorly active, but converted into a full agonist of
      chemerinR by proteolytic removal of the last six amino acids. In the present
      work, we have synthesized a number of peptides derived from the C-terminal domain
      of human prochemerin and have investigated their functional properties as
      agonists or antagonists of human chemerinR. We found that the nonapeptide
      (149)YFPGQFAFS(157) (chemerin-9), corresponding to the C terminus of processed
      chemerin, retained most of the activity of the full-size protein, with regard to
      agonism toward the chemerinR. Extension of this peptide at its N terminus did not
      increase the activity, whereas further truncations rapidly resulted in inactive
      compounds. The C-terminal end of the peptide appeared crucial for its activity,
      as addition of a single amino acid or removal of two amino acids modified the
      potency by four orders of magnitude. Alanine-scanning mutagenesis identified
      residues Tyr(149), Phe(150), Gly(152), Phe(154), and Phe(156) as the key
      positions for chemerinR activation. A modified peptide (YHSFFFPGQFAFS) was
      synthesized and iodinated, and a radioligand binding assay was established. It
      was found that the ability of the various peptides to activate the chemerin
      receptor was strictly correlated with their affinity in the binding assay. These
      results confirm that a precise C-terminal processing is required for the
      generation of a chemerinR agonist. The possibility to restrict a medium sized
      protein to a nonapeptide, while keeping a low nanomolar affinity for its receptor
      is unusual among G protein-coupled receptors ligands. The identification of these
      short bioactive peptides will considerably accelerate the pharmacological
      analysis of chemerin-chemerinR interactions.

PMID- 14701798
TI  - Endocytosis of hepatic lipase and lipoprotein lipase into rat liver hepatocytes
      in vivo is mediated by the low density lipoprotein receptor-related protein.
AB  - In isolated cell studies, the internalization and degradation of hepatic lipase
      (HL) has been linked to its binding to the low density lipoprotein receptor
      related protein (LRP). We have utilized the receptor-associated protein (RAP), a
      universal inhibitor of high affinity ligand binding to LRP, to evaluate the
      participation of LRP in the endocytosis of HL and lipoprotein lipase (LPL). We
      isolated a total endosome fraction from rat livers after a 30-min infusion of
      recombinant RAP, administered as a glutathione S-transferase conjugate (GST-RAP).
      GST-RAP infusion had no effect on the concentration of HL in liver homogenates,
      but its concentration in blood plasma increased progressively by 20%, and
      enrichment over homogenate of HL in endosomes was reduced by 50% as compared with
      infusion of GST alone. The concentrations of LPL in liver and plasma were 1.4 and
      0.5%, respectively, those of HL, but endosomal enrichment of the two enzymes was
      similar ( approximately 10-fold). GST-RAP infusion had no effect on the
      concentration of LPL in liver but increased its concentration in blood plasma by
      250% and reduced its endosomal enrichment by 95% or greater. GST-RAP infusion
      also reduced endosomal enrichment of LRP by 40%, but enrichment of several other
      endocytic receptors was unaffected. Endosomal enrichment of several membrane
      trafficking proteins associated with the endocytic pathway in hepatocytes was
      unaffected by GST-RAP with the exception of early endosome endosome antigen 1,
      which was reduced by 85%. We conclude that HL is partially and LPL almost
      exclusively taken up into rat hepatocytes after binding to the endocytic receptor
      LRP.

PMID- 14701799
TI  - Uncoupling of the signaling and caspase-inhibitory properties of X-linked
      inhibitor of apoptosis.
AB  - In addition to its well described function as an enzymatic inhibitor of specific
      caspases, X-linked inhibitor of apoptosis (X-linked IAP or XIAP) can function as
      a cofactor in Smad, NF-kappaB, and JNK signaling pathways. However, caspases
      themselves have been shown to regulate the activity of a number of signaling
      cascades, raising the possibility that the effect of XIAP in these pathways is
      indirect. Here we examine this question by introducing point mutations in XIAP
      predicted to disrupt the ability of the molecule to bind to and inhibit caspases.
      We show that whereas these mutant variants of XIAP lost caspase-inhibitory
      activity, they maintained their ability to activate Smad, NF-kappaB, and JNK
      signaling pathways. Indeed, the signaling properties of the molecule were mapped
      to domains not directly involved in caspase binding and inhibition. The
      activation of NF-kappaB by XIAP was dependent on the E3 ubiquitin ligase activity
      of the RING domain. On the other hand, the ability of XIAP to activate Smad
      dependent signaling was mapped to the third baculoviral IAP repeat (BIR) and loop
      regions of the molecule. Thus, the anti-apoptotic and signaling properties of
      XIAP can be uncoupled.

PMID- 14701800
TI  - Direct evidence for substrate-induced proton release in detergent-solubilized
      EmrE, a multidrug transporter.
AB  - A novel approach to study coupling of substrate and ion fluxes is presented. EmrE
      is an H(+)-coupled multidrug transporter from Escherichia coli. Detergent
      solubilized EmrE binds substrate with high affinity in a pH-dependent mode. Here
      we show, for the first time in an ion-coupled transporter, substrate-induced
      release of protons in a detergent-solubilized preparation. The direct
      measurements allow for an important quantitation of the phenomenon. Thus,
      stoichiometry of the release in the wild type and a mutant with a single carboxyl
      at position 14 is very similar and about 0.8 protons/monomer. The findings
      demonstrate that the only residue involved in proton release is a highly
      conserved membrane-embedded glutamate (Glu-14) and that all the Glu-14 residues
      in the EmrE functional oligomer participate in proton release. Furthermore, from
      the pH dependence of the release we determined the pK of Glu-14 as 8.5 and for an
      aspartate replacement at the same position as 6.7. The high pK of the carboxyl at
      position 14 is essential for coupling of fluxes of protons and substrates.

PMID- 14701801
TI  - Restricted expression and photic induction of a novel mouse regulatory factor X4
      transcript in the suprachiasmatic nucleus.
AB  - The regulatory factor X (RFX) family of transcription factors is characterized by
      a unique and highly conserved 76-amino acid residue DNA-binding domain. Mammals
      have five RFX genes, but the physiological functions of their products are
      unknown, with the exception of RFX5. Here a mouse RFX4 transcript was identified
      that encodes a peptide of 735 amino acids, including the DNA-binding domain. Its
      expression was localized in the suprachiasmatic nucleus, the central pacemaker
      site of the circadian clock. Also, light exposure was found to induce its gene
      expression in a subjective night-specific manner. Polyclonal antibodies were
      prepared, and an 80-kDa band was detected in the suprachiasmatic nucleus by
      Western hybridization. A histochemical study showed a localization of the
      products in the nucleus. This is the first report on mouse RFX4, which contains
      the RFX DNA-binding motif. Our investigation may provide clues to the
      physiological function of RFX4.

PMID- 14701802
TI  - Functional expression of the interleukin-11 receptor alpha-chain and evidence of
      antiapoptotic effects in human colonic epithelial cells.
AB  - A tissue-protective effect of interleukin-11 (IL-11) for the intestinal mucosa
      has been postulated from animal models of inflammatory bowel disease (IBD).
      Despite the fact that the clinical usefulness of the anti-inflammatory effects of
      this cytokine is presently investigated in patients with IBD, there are no data
      available regarding the target cells of IL-11 action and the mechanisms of tissue
      protection within the human colonic mucosa. IL-11 responsiveness is restricted to
      cells that express the interleukin-11 receptor alpha-chain (IL-11Ralpha) and an
      additional signal-transducing subunit (gp130). In this study, we identified the
      target cells for IL-11 within the human colon with a new IL-11Ralpha monoclonal
      antibody and investigated the functional expression of the receptor and
      downstream effects of IL-11-induced signaling. Immunohistochemistry revealed
      expression of the IL-11Ralpha selectively on colonic epithelial cells. HT-29 and
      colonic epithelial cells (CEC) constitutively expressed IL-11Ralpha mRNA and
      protein. Co-expression of the signal-transducing subunit gp130 was also
      demonstrated. IL-11 induced signaling through triggering activation of the Jak
      STAT pathway without inducing anti-inflammatory or proliferative effects in
      colonic epithelial cells. However, IL-11 stimulation resulted in a dose-dependent
      tyrosine phosphorylation of Akt, a decreased activation of caspase-9, and a
      reduced induction of apoptosis in cultured CEC. In HLA-B27 transgenic rats
      treated with IL-11, a reduction of apoptotic cell numbers was found. This study
      demonstrates functional expression of the IL-11Ralpha restricted on CEC within
      the human colonic mucosa. IL-11 induced signaling through triggering activation
      of the Jak-STAT pathway, without inducing anti-inflammatory or proliferative
      effects. The beneficial effects of IL-11 therapy are likely to be mediated by CEC
      via activation of the Akt-survival pathway, mediating antiapoptotic effects to
      support mucosal integrity.

PMID- 14701803
TI  - S-Nitrosation regulates the activation of endogenous procaspase-9 in HT-29 human
      colon carcinoma cells.
AB  - Nitric oxide-mediated signals have been suggested to regulate the activity of
      caspases negatively, yet literature has provided little direct evidence. We show
      in this paper that cytokines and nitric-oxide synthase (NOS) inhibitors regulate
      S-nitrosation of an initiator caspase, procaspase-9, in a human colon
      adenocarcinoma cell line, HT-29. A NOS inhibitor, N(G)-methyl-l-arginine,
      enhanced the tumor necrosis factor-alpha (TNF-alpha)-induced cleavage of
      procaspase-9, procaspase-3, and poly-(ADP-ribose) polymerase, as well as the
      level of apoptosis. N(G)-Methyl-l-arginine, however, did not affect the cleavage
      of procaspase-8. These results suggest that nitric oxide regulates the cleavage
      of procaspase-9 and its downstream proteins and, subsequently, apoptosis in HT-29
      cells. Labeling S-nitrosated cysteines with a biotin tag enabled us to reveal S
      nitrosation of endogenous procaspase-9 that was immunoprecipitated from the HT-29
      cell extracts. Furthermore, the treatment with TNF-alpha, as well as NOS
      inhibitors, decreased interferon-gamma-induced S-nitrosation in procaspase-9. Our
      results show that S-nitrosation of endogenous procaspase-9 occurs in the HT-29
      cells under normal conditions and that denitrosation of procaspase-9 enhances its
      cleavage and consequent apoptosis. We, therefore, suggest that S-nitrosation
      regulates activation of endogenous procaspase-9 in HT-29 cells.

PMID- 14701804
TI  - Control of human PIRH2 protein stability: involvement of TIP60 and the
      proteosome.
AB  - Murine PIRH2 (mPIRH2) was recently identified as a RING finger-containing
      ubiquitin-protein isopeptide ligase that interacts with both p53 and the human
      androgen receptor. mpirh2 is a p53-responsive gene that is up-regulated by UV,
      and mPIRH2 protein has the capacity to polyubiquitylate p53, perhaps leading to
      p53 destruction. mpirh2 therefore has properties similar to those of the oncogene
      mdm2. Here, we have identified human PIRH2 (hPIRH2) as a TIP60-interacting
      protein. To investigate its regulation, we characterized hPIRH2 in parallel with
      hPIRH2 variants possessing mutations of conserved RING finger residues. We
      observed that wild-type hPIRH2 is an unstable protein with a short half-life and
      is a target for RING domain-dependent proteasomal degradation. Accordingly, we
      found that hPIRH2 was ubiquitylated in cells. The TIP60-hPIRH2 association
      appeared to regulate hPIRH2 stability; coexpression of TIP60 enhanced hPIRH2
      protein stability and altered hPIRH2 subcellular localization. These results
      suggest that hPIRH2 activities can be controlled, at the post-translational
      level, in multiple ways.

PMID- 14701805
TI  - Mechanism of proton gating of a urea channel.
AB  - The size and complexity of many pH-gated channels have frustrated the development
      of specific structural models. The small acid-activated six-membrane segment urea
      channel of Helicobacter hepaticus (HhUreI), homologous to the essential UreI of
      the gastric pathogen Helicobacter pylori, enables identification of all the
      periplasmic sites of proton gating by site-directed mutagenesis. Exposure to
      external acidity enhances [(14)C]urea uptake by Xenopus oocytes expressing
      HhUreI, with half-maximal activity (pH(0.5)) at pH 6.8. A downward shift of
      pH(0.5) in single site mutants identified four of six protonatable periplasmic
      residues (His-50 at the boundary of the second transmembrane segment TM2, Glu-56
      in the first periplasmic loop, Asp-59 at the boundary of TM3, and His-170 at the
      boundary of TM6) that affect proton gating. Asp-59 was the only site at which a
      protonatable residue appeared to be essential for pH gating. Mutation of Glu-110
      or Glu-114 in PL2 did not affect the pH(0.5) of gating. A chimera, where the
      entire periplasmic domain of HhUreI was fused to the membrane domain of
      Streptococcus salivarius UreI (SsUreI), retained the pH-independent properties of
      SsUreI. Hence, proton gating of HhUreI likely depends upon the formation of
      hydrogen bonds by periplasmic residues that in turn produce conformational
      changes of the transmembrane domain. Further studies on HhUreI may facilitate
      understanding of other physiologically important pH-responsive channels.

PMID- 14701806
TI  - Characterization of Vta1p, a class E Vps protein in Saccharomyces cerevisiae.
AB  - We identified VTA1 in a screen for mutations that result in altered vacuole
      morphology. Deletion of VTA1 resulted in delayed trafficking of the lipophilic
      dye FM4-64 to the vacuole and altered vacuolar morphology when cells were exposed
      to the dye 5-(and 6)-carboxy-2',7'-dichlorofluorescein diacetate (CDCFDA).
      Deletion of class E vacuolar protein sorting (VPS) genes, which encode proteins
      that affect multivesicular body formation, also showed altered vacuolar
      morphology upon exposure to high concentrations of CDCFDA. These results suggest
      a VPS defect for Deltavta1 cells. Deletion of VTA1 did not affect growth on
      raffinose and only mildly affected carboxypeptidase S sorting. Turnover of the
      surface protein Ste3p, the a-factor receptor, was affected in Deltavta1 cells
      with the protein accumulating on the vacuolar membrane. Likewise the alpha-factor
      receptor Ste2p accumulated on the vacuolar membrane in Deltavta1 cells. We
      demonstrated that many class E VPS deletion strains are hyper-resistant to the
      cell wall disruption agent calcofluor white. Deletion of VTA1 or VPS60, another
      putative class E gene, resulted in calcofluor white hypersensitivity. A Vta1p
      green fluorescent protein fusion protein transiently associated with a Pep12p
      positive compartment. This localization was altered by deletion of many of the
      class E VPS genes, indicating that Vta1p binds to endosomes in a manner dependent
      on the assembly of the endosomal sorting complexes required for transport.
      Membrane-associated Vta1p co-purified with Vps60p, suggesting that Vta1p is a
      class E Vps protein that interacts with Vps60p on a prevacuolar compartment.

PMID- 14701807
TI  - The molecular chaperone, Atp12p, from Homo sapiens. In vitro studies with
      purified wild type and mutant (E240K) proteins.
AB  - Work in Saccharomyces cerevisiae has shown that Atp12p binds to unassembled alpha
      subunits of F(1) and in so doing prevents the alpha subunit from associating with
      itself in non-productive complexes during assembly of the F(1) moiety of the
      mitochondrial ATP synthase. We have developed a method to prepare recombinant
      Atp12p after expression of its human cDNA in bacterial cells. The molecular
      chaperone activity of HuAtp12p was studied using citrate synthase as a model
      substrate. Wild type HuAtp12p suppresses the aggregation of thermally inactivated
      citrate synthase. In contrast, the mutant protein HuAtp12p(E240K), which harbors
      a lysine at the position of the highly conserved Glu-240, fails to prevent
      citrate synthase aggregation at 43 degrees C. No significant differences were
      observed between the wild type and the mutant proteins as judged by sedimentation
      analysis, cysteine titration, tryptophan emission spectra, or limited
      proteolysis, which suggests that the E240K mutation alters the activity of
      HuAtp12p with minimal effects on the physical integrity of the protein. An
      additional important finding of this work is that the equilibrium chemical
      denaturation curve of HuAtp12p shows two components, the first of which is
      associated with protein aggregation. This result is consistent with a model for
      Atp12p structure in which there is a hydrophobic chaperone domain that is buried
      within the protein interior.

PMID- 14701808
TI  - Catalytic activity is required for calcium/calmodulin-dependent protein kinase IV
      to enter the nucleus.
AB  - Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a nuclear protein
      kinase that responds to acute rises in intracellular calcium by phosphorylating
      and activating proteins involved in transcription. Consistent with these roles,
      CaMKIV is found predominantly in the nucleus of cells in which it is expressed.
      Here we evaluate nuclear entry of CaMKIV and demonstrate that the protein kinase
      homology domain is both necessary and sufficient for nuclear localization.
      Unexpectedly, although catalytic activity is required for nuclear translocation,
      it is not required for CaMKIV to interact with the nuclear adaptor protein,
      importin-alpha. Because the catalytically inactive molecules remain in the
      cytoplasm, these data suggest that this interaction is not sufficient for nuclear
      entry. We evaluated a role for other proteins known to interact with CaMKIV in
      regulation of its nuclear entry. Although our data do not support a role for
      calmodulin or protein phosphatase 2A, the catalytically inactive CaMKIV proteins
      interact more avidly with CaM-dependent protein kinase kinase (CaMKK), which is
      restricted to the cytoplasm. We find that the catalytically inactive proteins do
      not inhibit nuclear entry of wild-type CaMKIV but do inhibit the ability of the
      wild-type protein kinase to stimulate cyclic AMP response element-binding protein
      mediated transcription. Because activation loop phosphorylation is required for
      the transcriptional roles of CaMKIV, these data suggest that CaMKK
      phosphorylation of CaMKIV may occur in the cytoplasm. We propose that
      sequestration of CaMKK may be the molecular mechanism by which catalytically
      inactive mutants of CaMKIV exert their "dominant-negative" functions within the
      cell.

PMID- 14701809
TI  - Ddb1 is required for the proteolysis of the Schizosaccharomyces pombe replication
      inhibitor Spd1 during S phase and after DNA damage.
AB  - Recently we showed that the Schizosaccharomyces pombe ddb1 gene plays a role in S
      phase progression. A mutant S. pombe strain lacking expression of the ddb1 gene
      exhibited slow replication through both early and late regions causing a slow S
      phase phenotype. We attributed the phenotypes in the ddb1 strain to an increased
      activity of the replication checkpoint kinase Cds1. However, the basis for a high
      basal Cds1 activity in the ddb1 strain was not clear. It was shown that Ddb1
      associates with the Cop9/signalosome. Moreover, the phenotypes of the Deltaddb1
      strain are remarkably similar to the Deltacsn1 (or Deltacsn2) strain that lacks
      expression of the Csn1 (or Csn2) subunit of the Cop9/signalosome.
      Cop9/signalosome cooperates with Pcu4 to induce proteolysis of Spd1, which
      inhibits DNA replication by inhibiting ribonucleotide reductase. Therefore, we
      investigated whether Ddb1 is required for the proteolysis of Spd1. Here we show
      that a S. pombe strain lacking expression of Ddb1 fails to induce proteolysis of
      Spd1 in S phase and after DNA damage. Moreover, deletion of the spd1 gene
      attenuates the Cds1 kinase activity in cells lacking the expression of ddb1,
      suggesting that an accumulation of Spd1 results in the increase of Cds1 activity
      in the Deltaddb1 strain. In addition, the double mutant lacking spd1 and ddb1 no
      longer exhibits the growth defects and DNA damage sensitivity observed in the
      Deltaddb1 strain. Our results establish an essential role of Ddb1 in the
      proteolysis of Spd1. In addition, the observation provides evidence for a
      functional link between Ddb1 and the Cop9/signalosome.

PMID- 14701810
TI  - Real time analysis of STAT3 nucleocytoplasmic shuttling.
AB  - The transcription factor STAT3 is most important for the signal transduction of
      interleukin-6 and related cytokines. Upon stimulation cytoplasmic STAT3 is
      phosphorylated at tyrosine 705, translocates into the nucleus, and induces target
      genes. Notably, STAT proteins are also detectable in the nuclei of unstimulated
      cells. In this report we introduce a new method for the real time analysis of
      STAT3 nucleocytoplasmic shuttling in living cells which is based on the recently
      established fluorescence localization after photobleaching (FLAP) approach. STAT3
      was C-terminally fused with the cyan (CFP) and yellow (YFP) variants of the green
      fluorescent protein. In the resulting STAT3-CFP-YFP (STAT3-CY) fusion protein the
      YFP can be selectively bleached using the 514-nm laser of a confocal microscope.
      This setting allows studies on the dynamics of STAT3 nucleocytoplasmic transport
      by monitoring the subcellular distribution of fluorescently labeled and
      selectively bleached STAT3-CY. By this means we demonstrate that STAT3-CY
      shuttles continuously between the cytosol and the nucleus in unstimulated cells.
      This constitutive shuttling does not depend on the phosphorylation of tyrosine
      705 because a STAT3(Y705F)-CY mutant shuttles to the same extent as STAT3-CY.
      Experiments with deletion mutants reveal that the N-terminal moiety of STAT3 is
      essential for shuttling. Further studies suggest that a decrease in STAT3 nuclear
      export contributes to the nuclear accumulation of STAT3 in response to cytokine
      stimulation. The new approach presented in this study is generally applicable to
      any protein of interest for analyzing nucleocytoplasmic transport mechanisms in
      real time.

PMID- 14701811
TI  - Schizosaccharomyces pombe carboxyl-terminal domain (CTD) phosphatase Fcp1:
      distributive mechanism, minimal CTD substrate, and active site mapping.
AB  - Schizosaccharomyces pombe Fcp1 is an essential protein serine phosphatase that
      preferentially dephosphorylates Ser(2) of the RNA polymerase II C-terminal domain
      (CTD) heptad repeat Y(1)S(2)P(3)T(4)S(5)P(6)S(7). Here we show that: (i) Fcp1
      acts distributively during the hydrolysis of substrates containing tandem Ser(2)
      PO(4) heptads; (ii) the minimal optimal CTD substrate for Fcp1 is a single heptad
      of phasing S(5)P(6)S(7)Y(1)S(2)P(3)T(4); and (iii) single alanine mutations of
      flanking residues Tyr(1) or Pro(3) result in 6-fold decrements in CTD phosphatase
      activity. Fcp1 belongs to the DXDX(T/V) family of phosphotransferases that act
      via an acyl-phosphoenzyme intermediate. An alanine scan of 11 conserved positions
      of S. pombe Fcp1 identifies Thr(174), Tyr(237), Thr(243), and Tyr(249) as
      important for phosphatase activity. Structure-activity relationships at these
      positions were determined by introducing conservative substitutions. Our results,
      together with previous mutational studies, highlight a constellation of 11 amino
      acids that are conserved in all Fcp1 orthologs and likely comprise the active
      site.

PMID- 14701812
TI  - Depletion of pre-beta-high density lipoprotein by human chymase impairs ATP
      binding cassette transporter A1- but not scavenger receptor class B type I
      mediated lipid efflux to high density lipoprotein.
AB  - The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cellular
      unesterified cholesterol and phospholipid to lipid-poor apolipoprotein A-I.
      Chymase, a protease secreted by mast cells, selectively cleaves pre-beta
      migrating particles from high density lipoprotein (HDL)(3) and reduces the efflux
      of cholesterol from macrophages. To evaluate whether this effect is the result of
      reduction of ABCA1-dependent or -independent pathways of cholesterol efflux, in
      this study we examined the efflux of cholesterol to preparations of chymase
      treated HDL(3) in two types of cell: 1) in J774 murine macrophages endogenously
      expressing low levels of scavenger receptor class B, type I (SR-BI), and high
      levels of ABCA1 upon treatment with cAMP; and 2) in Fu5AH rat hepatoma cells
      endogenously expressing high levels of the SR-BI and low levels of ABCA1.
      Treatment of HDL(3) with the human chymase resulted in rapid depletion of pre
      beta-HDL and a concomitant decrease in the efflux of cholesterol and phospholipid
      (2-fold and 3-fold, respectively) from the ABCA1-expressing J774 cells. In
      contrast, efflux of free cholesterol from Fu5AH to chymase-treated and to
      untreated HDL(3) was similar. Incubation of HDL(3) with phospholipid transfer
      protein led to an increase in pre-beta-HDL contents as well as in ABCA1-mediated
      cholesterol efflux. A decreased cholesterol efflux to untreated HDL(3) but not to
      chymase-treated HDL(3) was observed in ABCA1-expressing J774 with probucol, an
      inhibitor of cholesterol efflux to lipid-poor apoA-I. Similar results were
      obtained using brefeldin and gliburide, two inhibitors of ABCA1-mediated efflux.
      These results indicate that chymase treatment of HDL(3) specifically impairs the
      ABCA1-dependent pathway without influencing either aqueous or SR-BI-facilitated
      diffusion and that this effect is caused by depletion of lipid-poor pre-beta
      migrating particles in HDL(3). Our results are compatible with the view that
      HDL(3) promotes ABCA1-mediated lipid efflux entirely through its lipid-poor
      fraction with pre-beta mobility.

PMID- 14701813
TI  - Tumor necrosis factor-induced nonapoptotic cell death requires receptor
      interacting protein-mediated cellular reactive oxygen species accumulation.
AB  - The mechanism of tumor necrosis factor (TNF)-induced nonapoptotic cell death is
      largely unknown, although the mechanism of TNF-induced apoptosis has been studied
      extensively. In wild-type mouse embryonic fibroblast cells under a caspase
      inhibited condition, TNF effectively induced cell death that morphologically
      resembled necrosis. In this study, we utilized gene knockout mouse embryonic
      fibroblasts cells and found that tumor necrosis factor receptor (TNFR) I mediates
      TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical
      components of the signaling cascade of this TNF-induced necrotic cell death.
      Inhibitors of NF-kappaB facilitated TNF-induced necrotic cell death, suggesting
      that NF-kappaB suppresses the necrotic cell death pathway. JNK, p38, and ERK
      activation seem not to be required for this type of cell death because mitogen
      activated protein kinase inhibitors did not significantly affect TNF-induced
      necrotic cell death. In agreement with the previous reports that the reactive
      oxygen species (ROS) may play an important role in this type of cell death, the
      ROS scavenger butylated hydroxyanisole efficiently blocked TNF-induced necrotic
      cell death. Interestingly, during TNF-induced necrotic cell death, the cellular
      ROS level was significantly elevated in wild type, but not in RIP(-/-), TRAF2(-/
      ), and FADD(-/-) cells. These results suggest that RIP, TRAF2, and FADD are
      crucial in mediating ROS accumulation in TNF-induced necrotic cell death.

PMID- 14701814
TI  - The preferred pathway of glycosaminoglycan-accelerated inactivation of thrombin
      by heparin cofactor II.
AB  - Thrombin (T) inactivation by the serpin, heparin cofactor II (HCII), is
      accelerated by the glycosaminoglycans (GAGs) dermatan sulfate (DS) and heparin
      (H). Equilibrium binding and thrombin inactivation kinetics at pH 7.8 and ionic
      strength (I) 0.125 m demonstrated that DS and heparin bound much tighter to
      thrombin (K(T(DS)) 1-5.8 microm; K(T(H)) 0.02-0.2 microm) than to HCII
      (K(HCII(DS)) 236-291 microm; K(HCII(H)) 25-35 microm), favoring formation of
      T.GAG over HCII.GAG complexes as intermediates for T.GAG.HCII complex assembly.
      At [GAG] << K(HCII(GAG)) the GAG and HCII concentration dependences of the first
      order inactivation rate constants (k(app)) were hyperbolic, reflecting saturation
      of T.GAG complex and formation of the T.GAG.HCII complex from T.GAG and free
      HCII, respectively. At [GAG] >> K(HCII(GAG)), HCII.GAG complex formation caused a
      decrease in k(app). The bell-shaped logarithmic GAG dependences fit an obligatory
      template mechanism in which free HCII binds GAG in the T.GAG complex. DS and
      heparin bound fluorescently labeled meizothrombin(des-fragment 1) (MzT(-F1)) with
      K(MzT(-F1)(GAG)) 10 and 20 microm, respectively, demonstrating a binding site
      outside of exosite II. Exosite II ligands did not attenuate the DS-accelerated
      thrombin inactivation markedly, but DS displaced thrombin from heparin-Sepharose,
      suggesting that DS and heparin share a restricted binding site in or nearby
      exosite II, in addition to binding outside exosite II. Both T.DS and MzT(-F1).DS
      interactions were saturable at DS concentrations substantially below K(HCII(DS)),
      consistent with DS bridging T.DS and free HCII. The results suggest that GAG
      template action facilitates ternary complex formation and accommodates HCII
      binding to GAG and thrombin exosite I in the ternary complex.

PMID- 14701815
TI  - Serpin mechanism of hepatitis C virus nonstructural 3 (NS3) protease inhibition:
      induced fit as a mechanism for narrow specificity.
AB  - Hepatitis C virus (HCV) nonstructural 3 (NS3) serine protease disrupts important
      cellular antiviral signaling pathways and plays a pivotal role in the proteolytic
      maturation of the HCV polyprotein precursor. This recent discovery has fostered
      the search for NS3 protease inhibitors. However, the enzyme's unusual induced fit
      behavior and peculiar molecular architecture have imposed considerable obstacles
      to the development of small molecule inhibitors. In this article, we demonstrate
      that such unique induced fit behavior and the chymotrypsin-like catalytic domain
      can provide the structural plasticity necessary to generate protein-based
      inhibitors of the NS3 protease. We took advantage of the macromolecular scaffold
      of a Drosophila serpin, SP6, which intrinsically supports chymotrypsin-like
      enzyme inhibition, to design a novel class of potent and selective inhibitors. We
      show that altering the SP6 reactive site loop (RSL) resulted in the development
      of the first effective (K(i) of 34 nm) and selective serpin, SP6(EVC/S), directed
      at the NS3 protease. SP6(EVC/S) operates as a suicide substrate inhibitor, and
      its partitioning between the complex-forming and proteolytic pathways for the NS3
      protease is HCV NS4A cofactor-dependent and -specific. Once bound to the protease
      active site, SP6(EVC/S) partitions with equal probability to undergo proteolysis
      by NS3 at the C-terminal site of the engineered RSL, (P(6))Glu-Ile-(P(4))Val-Met
      Thr-(P(1))Cys- downward arrow -(P(1)')Ser, or to form a covalent acyl-enzyme
      complex characteristic of cognate protease-serpin pairs. Our results also reveal
      a novel cofactor-induced serpin mechanism of enzyme inhibition that could be
      explored for developing effective and selective inhibitors of other important
      induced fit viral proteases of the Flaviviridae family such as the West Nile
      virus NS3 endoprotease.

PMID- 14701816
TI  - Recombinant phospholipase Czeta has high Ca2+ sensitivity and induces Ca2+
      oscillations in mouse eggs.
AB  - Sperm-specific phospholipase Czeta (PLCzeta) is known to induce intracellular
      Ca(2+) oscillations and subsequent early embryonic development when expressed in
      mouse eggs by injection of RNA encoding PLCzeta (Saunders, C. M., Larman, M. G.,
      Parrington, J., Cox, L. J., Royse, J., Blayney, L. M., Swann, K., and Lai, F. A.
      (2002) Development 129, 3533-3544). The present study addressed characteristics
      of purified mouse PLCzeta protein that was synthesized using the baculovirus/Sf9
      cell expression system. Microinjection of recombinant PLCzeta protein into mouse
      eggs induced serial Ca(2+) spikes quite similar to those produced by the
      injection of sperm extract, probably because of repetitive Ca(2+) release from
      the endoplasmic reticulum caused by continuously produced inositol 1,4,5
      trisphosphate. Recombinant PLCdelta1 also induced Ca(2+) oscillations, but a 20
      fold higher concentration was required compared with PLCzeta. In the enzymatic
      assay of phosphatidylinositol 4,5-bisphosphate hydrolyzing activity in vitro at
      various calcium ion concentrations ([Ca(2+)]), PLCzeta exhibited a significant
      activity at [Ca(2+)] as low as 10 nm and had 70% maximal activity at 100 nm
      [Ca(2+)] that is usually the basal intracellular calcium ion concentration level
      of cells. On the other hand, the activity of PLCdelta1 increased at a [Ca(2+)]
      between 1 and 30 microm. EC(50) was 52 nm for PLCzeta and 5.7 microm for
      PLCdelta1. Thus, PLCzeta has an approximately 100-fold higher Ca(2+) sensitivity
      than PLCdelta1. The ability of purified PLCzeta protein to induce Ca(2+)
      oscillations qualifies PLCzeta as a proper candidate of the mammalian egg
      activating sperm factor. Furthermore, such a high Ca(2+) sensitivity of PLC
      activity as PLCzeta that can be active in cells at the resting state is thought
      to be an appropriate characteristic of the sperm factor, which is introduced into
      the ooplasm upon sperm-egg fusion, triggers Ca(2+) release first, and maintains
      Ca(2+) oscillations.

PMID- 14701817
TI  - Yeast Coq5 C-methyltransferase is required for stability of other polypeptides
      involved in coenzyme Q biosynthesis.
AB  - Coenzyme Q (Q) functions in the electron transport chain of both prokaryotes and
      eukaryotes. The biosynthesis of Q requires a number of steps involving at least
      eight Coq polypeptides. Coq5p is required for the C-methyltransferase step in Q
      biosynthesis. In this study we demonstrate that Coq5p is peripherally associated
      with the inner mitochondrial membrane on the matrix side. Phenotypic
      characterization of a collection of coq5 mutant yeast strains indicates that
      while each of the coq5 mutant strains are rescued by the Saccharomyces cerevisiae
      COQ5 gene, only the coq5-2 and coq5-5 mutants are rescued by expression of
      Escherichia coli ubiE, a homolog of COQ5. The coq5-2 and coq5-5 mutants contain
      mutations within or adjacent to conserved methyltransferase motifs that would be
      expected to disrupt the catalysis of C-methylation. The steady state levels of
      the Coq5-2 and Coq5-5 mutant polypeptides are not decreased relative to wild type
      Coq5p. Two other polypeptides required for Q biosynthesis, Coq3p and Coq4p, are
      detected in the wild type parent and in the coq5-2 and coq5-5 mutants, but are
      not detected in the coq5-null mutant, or in the coq5-4 or coq5-3 mutants. The
      effect of the coq5-4 mutation is similar to a null, since it results in a stop
      codon at position 93. However, the coq5-3 mutation (G304D) is located just four
      amino acids away from the C terminus. While C-methyltransferase activity is
      detectable in mitochondria isolated from this mutant, the steady state level of
      Coq5p is dramatically decreased. These studies show that at least two functions
      can be attributed to Coq5p; first, it is required to catalyze the C
      methyltransferase step in Q biosynthesis and second, it is involved in
      stabilizing the Coq3 and Coq4 polypeptides required for Q biosynthesis.

PMID- 14701819
TI  - Novel organization and properties of annexin 2-membrane complexes.
AB  - Annexin 2 belongs to the annexin family of proteins that bind to phospholipid
      membranes in a Ca(2+)-dependent manner. Here we show that, under mild acidic
      conditions, annexin 2 binds to and aggregates membranes containing anionic
      phospholipids, a fact that questions the mechanism of its interaction with
      membranes via Ca(2+) bridges only. The H(+) sensitivity of annexin 2-mediated
      aggregation is modulated by lipid composition (i.e. cholesterol content). Cryo
      electron microscopy of aggregated liposomes revealed that both the monomeric and
      the tetrameric forms of the protein form bridges between the liposomes at acidic
      pH. Monomeric annexin 2 induced two different organizations of the membrane
      junctions. The first resembled that obtained at pH 7 in the presence of Ca(2+).
      For the tetramer, the arrangement was different. These bridges seemed more
      flexible than the Ca(2+)-mediated junctions allowing the invagination of
      membranes. Time-resolved fluorescence analysis at mild acidic pH and the
      measurement of Stokes radius revealed that the protein undergoes conformational
      changes similar to those induced by Ca(2+). Labeling with the lipophilic probe 3
      (trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine indicated that the protein
      has access to the hydrophobic part of the membrane at both acidic pH in the
      absence of Ca(2+) and at neutral pH in the presence of Ca(2+). Models for the
      membrane interactions of annexin 2 at neutral pH in the presence of Ca(2+) and at
      acidic pH are discussed.

PMID- 14701818
TI  - Two zebrafish eIF4E family members are differentially expressed and functionally
      divergent.
AB  - Eukaryotic translation initiation factor 4E (eIF4E) is an essential component of
      the translational machinery that binds m(7)GTP and mediates the recruitment of
      capped mRNAs by the small ribosomal subunit. Recently, a number of proteins with
      homology to eIF4E have been reported in plants, invertebrates, and mammals.
      Together with the prototypical translation factor, these constitute a new family
      of structurally related proteins. To distinguish the prototypical translation
      factor eIF4E from other family members, it has been termed eIF4E-1 (Keiper, B.
      D., Lamphear, B. J., Deshpande, A. M., Jankowska-Anyszka, M., Aamodt, E. J.,
      Blumenthal, T., and Rhoads, R. E. (2000) J. Biol. Chem. 275, 10590-10596). We
      describe the characterization of two eIF4E family members in the zebrafish Danio
      rerio. Based on their relative identities with human eIF4E-1, these zebrafish
      proteins are termed eIF4E-1A (82%) and eIF4E-1B (66%). eIF4E-1B, originally
      termed eIF4E(L), has been reported previously as the zebrafish eIF4E-1
      counterpart (Fahrenkrug, S. C., Dahlquist, M. O., Clark, K., and Hackett, P. B.
      (1999) Differentiation 65, 191-201; Fahrenkrug, S. C., Joshi, B., Hackett, P. B.,
      and Jagus, R. (2000) Differentiation 66, 15-22). Sequence comparisons suggest
      that the two genes probably evolved from a duplication event that occurred during
      vertebrate evolution. eIF4E-1A is expressed ubiquitously in zebrafish, whereas
      expression of eIF4E-1B is restricted to early embryonic development and to gonads
      and muscle of the tissues investigated. The ability of these two zebrafish
      proteins to bind m(7)GTP, eIF4G, and 4E-BP, as well as to complement yeast
      conditionally deficient in functional eIF4E, show that eIF4E-1A is a functional
      equivalent of human eIF4E-1. Surprisingly, although eIF4E-1B possesses all known
      residues thought to be required for interaction with the cap structure, eIF4G,
      and 4E-BPs, it fails to interact with any of these components, suggesting that
      this protein serves a role other than that assigned to eIF4E.

PMID- 14701820
TI  - Deletion of a negatively acting sequence in a chimeric GATA-1 enhancer-long
      terminal repeat greatly increases retrovirally mediated erythroid expression.
AB  - The locus control region of the beta-globin gene cluster has been used previously
      to direct erythroid expression of globin genes from retroviral vectors for the
      purpose of gene therapy. Short erythroid regulatory elements represent a
      potentially valuable alternative to the locus control region. Among them, the
      GATA-1 enhancer HS2 was used to replace the retroviral enhancer within the 3'
      long terminal repeat (LTR) of the retroviral vector SFCM, converting it into an
      erythroid-specific regulatory element. In this work, we have functionally studied
      an additional GATA-1 enhancer, HS1. HS1 participates in the transcriptional
      autoregulation of GATA-1 through an essential GATA-binding site that is
      footprinted in vivo. In this work we identified within HS1 a new in vivo
      footprinted region, and we showed that this sequence indeed binds a nuclear
      protein in vitro. Addition of HS1 to HS2 within the LTR of SFCM significantly
      improves the expression of a reporter gene. The deletion of the newly identified
      footprinted sequence in the retroviral construct further increases expression up
      to a level almost equal to that of the wild type retroviral LTR, without loss of
      erythroid specificity, suggesting that this sequence may act as a negative
      regulatory element. An improved vector backbone, MDeltaN, allows even better
      expression from the new GATA cassette. These results suggest that substantial
      improvement of overall expression can be achieved by the combination of multiple
      changes in both regulatory elements and vectors.

PMID- 14701821
TI  - Molecular dissection of the alpha-dystroglycan- and integrin-binding sites within
      the globular domain of human laminin-10.
AB  - The adhesive interactions of cells with laminins are mediated by integrins and
      non-integrin-type receptors such as alpha-dystroglycan and syndecans. Laminins
      bind to these receptors at the C-terminal globular domain of their alpha chains,
      but the regions recognized by these receptors have not been mapped precisely. In
      this study, we sought to locate the binding sites of laminin-10
      (alpha5beta1gamma1) for alpha(3)beta(1) and alpha(6)beta(1) integrins and alpha
      dystroglycan through the production of a series of recombinant laminin-10
      proteins with deletions of the LG (laminin G-like) modules within the globular
      domain. We found that deletion of the LG4-5 modules did not compromise the
      binding of laminin-10 to alpha(3)beta(1) and alpha(6)beta(1) integrins but
      completely abrogated its binding to alpha-dystroglycan. Further deletion up to
      the LG3 module resulted in loss of its binding to the integrins, underlining the
      importance of LG3 for integrin binding by laminin-10. When expressed individually
      as fusion proteins with glutathione S-transferase or the N-terminal 70-kDa region
      of fibronectin, only LG4 was capable of binding to alpha-dystroglycan, whereas
      neither LG3 nor any of the other LG modules retained the ability to bind to the
      integrins. Site-directed mutagenesis of the LG3 and LG4 modules indicated that
      Asp-3198 in the LG3 module is involved in the integrin binding by laminin-10,
      whereas multiple basic amino acid residues in the putative loop regions are
      involved synergistically in the alpha-dystroglycan binding by the LG4 module.

PMID- 14701822
TI  - The Escherichia coli transcriptional regulator MarA directly represses
      transcription of purA and hdeA.
AB  - The Escherichia coli MarA protein mediates a response to multiple environmental
      stresses through the activation or repression in vivo of a large number of
      chromosomal genes. Transcriptional activation for a number of these genes has
      been shown to occur via direct interaction of MarA with a 20-bp degenerate
      asymmetric "marbox" sequence. It was not known whether repression by MarA was
      also direct. We found that purified MarA was sufficient in vitro to repress
      transcription of both purA and hdeA. Transcription and electrophoretic mobility
      shift experiments in vitro using mutant promoters suggested that the marbox
      involved in the repression overlapped the -35 promoter motif and was in the
      "backward" orientation. This organization contrasts with that of the class II
      promoters activated by MarA, in which the marbox also overlaps the -35 motif but
      is in the "forward" orientation. We conclude that MarA, a member of the AraC/XylS
      family, can act directly as a repressor or an activator, depending on the
      position and orientation of the marbox within a promoter.

PMID- 14701823
TI  - pH Dependency and desensitization kinetics of heterologously expressed
      combinations of acid-sensing ion channel subunits.
AB  - The exact subunit combinations of functional native acid-sensing ion channels
      (ASICs) have not been established yet, but both homomeric and heteromeric
      channels are likely to exist. To determine the ability of different subunits to
      assemble into heteromeric channels, a number of ASIC1a-, ASIC1b-, ASIC2a-, ASIC2b
      , and ASIC3-containing homo- and heteromeric channels were studied by whole-cell
      patch clamp recordings with respect to pH sensitivity, desensitization kinetics,
      and level of sustained current normalized to peak current. Analyzing and
      comparing data for these three features demonstrated unique heteromeric channels
      in a number of co-expression experiments. Formation of heteromeric ASIC1a+2a and
      ASIC1b+2a channels was foremost supported by the desensitization characteristics
      that were independent of proton concentration, a feature none of the respective
      homomeric channels has. Several lines of evidence supported formation of
      ASIC1a+3, ASIC1b+3, and ASIC2a+3 heteromeric channels. The most compelling was
      the desensitization characteristics, which, besides being proton-independent,
      were faster than those of any of the respective homomeric channels. ASIC2b, which
      homomerically expressed is not activated by protons per se, did not appear to
      form unique heteromeric combinations with other subunits and in fact appeared to
      suppress the function of ASIC1b. Co-expression of three subunits such as
      ASIC1a+2a+3 and ASIC1b+2a+3 resulted in data that could best be explained by
      coexistence of multiple channel populations within the same cell. This
      observation seems to be in good agreement with the fact that ASIC-expressing
      sensory neurons display a variety of acid-evoked currents.

PMID- 14701824
TI  - Apolipoprotein A-I activates cellular cAMP signaling through the ABCA1
      transporter.
AB  - It has been suggested that the signal transduction pathway initiated by apoA-I
      activates key proteins involved in cellular lipid efflux. We investigated apoA-I
      mediated cAMP signaling in cultured human fibroblasts induced with (22R)
      hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Treatment of
      stimulated fibroblasts with apoA-I for short periods of time (<or=45 min)
      increased ATP binding cassette A1 (ABCA1) phosphorylation in a concentration
      dependent manner. Concomitantly, apoA-I increased the intracellular level of cAMP
      in a concentration- and time-dependent manner. The maximal cAMP level was reached
      within 10 min at 10 microg/ml apoA-I representing a 1-fold increase. The ability
      of apoA-I to mediate cAMP production was only observed in stimulated fibroblasts.
      Furthermore, overexpression of ABCA1 in Chinese hamster ovary cells resulted in a
      1.5-fold increase in apoA-I-mediated cAMP accumulation as compared with
      untransfected cells. In contrast, forskolin increased cAMP production
      significantly in unstimulated fibroblasts as well as in untransfected Chinese
      hamster ovary cells. Pharmacological inhibition of protein kinase A (H89)
      completely blocked apoA-I-mediated ABCA1 phosphorylation. Naturally occurring
      mutations of ABCA1 associated with Tangier disease (C1477R, 2203X, and 2145X)
      severely reduced apoA-I-mediated cAMP production, ABCA1 phosphorylation, (125)I
      apoA-I binding, and lipid efflux, without affecting forskolin-mediated cAMP
      elevation. In contrast, the protein kinase A catalytic subunit was able to
      phosphorylate ABCA1 similarly from mutant and normal cell lines in vitro.
      Together, our results indicate that apoA-I activates ABCA1 phosphorylation
      through the cAMP/protein kinase A-dependent pathway, apoA-I-mediated cAMP
      production required high level expression of functional ABCA1, and Tangier
      disease mutants have defective apoA-I-mediated cAMP signaling. These findings
      suggest that apoA-I may activate cAMP signaling through G protein-coupled ABCA1
      transporter.

PMID- 14701825
TI  - Structural insight into arginine degradation by arginine deiminase, an
      antibacterial and parasite drug target.
AB  - l-Arginine deiminase (ADI) catalyzes the irreversible hydrolysis of arginine to
      citrulline and ammonia. ADI is involved in the first step of the most widespread
      anaerobic route of arginine degradation. ADI, missing in high eukaryotes, is a
      potential antimicrobial and antiparasitic drug target. We have determined the
      crystal structure of ADI from Pseudomonas aeruginosa by the multi-wavelength
      anomalous diffraction method at 2.45 A resolution. The structure exhibits
      similarity to other arginine-modifying or substituted arginine-modifying enzymes
      such as dimethylarginine dimethylaminohydrolase (DDAH), arginine:glycine
      amidinotransferase, and arginine:inosamine-phosphate amidinotransferase, despite
      the lack of significant amino acid sequence homology to these enzymes. The
      similarity spans a core domain comprising five betabetaalphabeta motifs arranged
      in a circle around a 5-fold pseudosymmetry axis. ADI contains an additional alpha
      helical domain of novel topology inserted between the first and the second
      betabetaalphabeta modules. A catalytic triad, Cys-His-Glu/Asp (arranged in a
      different manner from that of the thiol proteases), seen in the other arginine
      modifying enzymes is also conserved in ADI, as well as many other residues
      involved in substrate binding. Based on this conservation pattern and the
      assumption that the substrate binding mode is similar to that of DDAH, an ADI
      catalytic mechanism is proposed. The main players are Cys-406, which mounts the
      nucleophilic attack on the carbon atom of the guanidinium group of arginine, and
      His-278, which serves as a general base.

PMID- 14701826
TI  - Activation of cyclin-dependent kinase 2 by full length and low molecular weight
      forms of cyclin E in breast cancer cells.
AB  - Cyclin E, a positive regulator of the cell cycle, controls the transition of
      cells from G(1) to S phase. Deregulation of the G(1)-S checkpoint contributes to
      uncontrolled cell division, a hallmark of cancer. We have reported previously
      that cyclin E is overexpressed in breast cancer and such overexpression is
      usually accompanied by the appearance of low molecular weight isoforms of cyclin
      E protein, which are not present in normal cells. Furthermore, we have shown that
      the expression of cyclin E low molecular weight isoforms can be used as a
      reliable prognostic marker for breast cancer to predict patient outcome. In this
      study we examined the role of cyclin E in directly activating cyclin-dependent
      kinase (CDK) 2. For this purpose, a series of N-terminal deleted forms of cyclin
      E corresponding to the low molecular weight forms detected only in cancer cells
      were translated in vitro and mixed with cell extracts. These tumor-specific N
      terminal deleted forms of cyclin E are able to activate CDK2. Addition of cyclin
      E into both normal and tumor cell extracts was shown to increase the levels of
      CDK2 activity, along with an increase in the amount of phosphorylated CDK2. The
      increase in CDK2 activity was because of cyclin E binding to endogenous CDK2 in
      complex with endogenous cyclin E, cyclin A, or unbound CDK2. The increase in CDK2
      phosphorylation was through a pathway involving cyclin-activating kinase, but
      addition of cyclin E to an extract containing unphosphorylated CDK2 can still
      lead to increase in CDK2 activity. Our data suggest that the ability of high
      levels of full-length and low molecular weight forms of cyclin E to activate CDK2
      may be one mechanism that leads to the constitutive activation of cyclin E.CDK2
      complexes leading to G(1)/S deregulation and tumor progression.

PMID- 14701827
TI  - Extracellular zinc and ATP restore chloride secretion across cystic fibrosis
      airway epithelia by triggering calcium entry.
AB  - Cystic fibrosis (CF) is caused by defective cyclic AMP-dependent cystic fibrosis
      transmembrane conductance regulator Cl(-) channels. Thus, CF epithelia fail to
      transport Cl(-) and water. A postulated therapeutic avenue in CF is activation of
      alternative Ca(2+)-dependent Cl(-) channels. We hypothesized that stimulation of
      Ca(2+) entry from the extracellular space could trigger a sustained Ca(2+) signal
      to activate Ca(2+)-dependent Cl(-) channels. Cytosolic [Ca(2+)](i) was measured
      in non-polarized human CF (IB3-1) and non-CF (16HBE14o(-)) airway epithelial
      cells. Primary human CF and non-CF airway epithelial monolayers as well as Calu-3
      monolayers were used to assess anion secretion. In vivo nasal potential
      difference measurements were performed in non-CF and two different CF mouse
      (DeltaF508 homozygous and bitransgenic gut-corrected but lung-null) models. Zinc
      and ATP induced a sustained, reversible, and reproducible increase in cytosolic
      Ca(2+) in CF and non-CF cells with chemistry and pharmacology most consistent
      with activation of P2X purinergic receptor channels. P2X purinergic receptor
      channel-mediated Ca(2+) entry stimulated sustained Cl(-) and HCO(3)(-) secretion
      in CF and non-CF epithelial monolayers. In non-CF mice, zinc and ATP induced a
      significant Cl(-) secretory response similar to the effects of agonists that
      increase intracellular cAMP levels. More importantly, in both CF mouse models,
      Cl(-) permeability of nasal epithelia was restored in a sustained manner by zinc
      and ATP. These effects were reversible and reacquirable upon removal and
      readdition of agonists. Our data suggest that activation of P2X calcium entry
      channels may have profound therapeutic benefit for CF that is independent of
      cystic fibrosis transmembrane conductance regulator genotype.

PMID- 14701829
TI  - Cross-talk between Cys34 and lysine residues in human serum albumin revealed by N
      homocysteinylation.
AB  - Protein N-homocysteinylation involves a post-translational modification by
      homocysteine (Hcy)-thiolactone. In humans, about 70% of circulating Hcy is N
      linked to blood proteins, mostly to hemoglobin and albumin. It was unclear what
      protein site(s) were prone to Hcy attachment and how N-linked Hcy affected
      protein function. Here we show that Lys(525) is a predominant site of N
      homocysteinylation in human serum albumin in vitro and in vivo. We also show that
      the reactivity of albumin lysine residues, including Lys(525), is affected by the
      status of Cys(34). The disulfide forms of circulating albumin, albumin-Cys(34)-S
      S-Cys and albumin-Cys(34)-S-S-Hcy, are N-homocysteinylated faster than albumin
      Cys(34)-SH. Although N-homocysteinylations of albumin-Cys(34)-SH and albumin
      Cys(34)-S-S-Cys yield different primary products, subsequent thiol-disulfide
      exchange reactions result in the formation of a single product, N-(Hcy-S-S-Cys)
      albumin-Cys(34)-SH. We also show that N-homocysteinylation affects the
      susceptibility of albumin to oxidation and proteolysis. The data suggest that a
      disulfide at Cys(34) of albumin promotes conversion of N-(Hcy-SH)-albumin-Cys(34)
      SH to a proteolytically sensitive form N-(Hcy-S-S-Cys)-albumin-Cys(34)-SH, which
      would facilitate clearance of the N-homocysteinylated form of mercaptoalbumin.

PMID- 14701828
TI  - Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in
      vivo.
AB  - Bone morphogenetic proteins (BMPs) are required for normal postnatal bone
      formation and osteoblast differentiation. There is evidence from recent studies
      that BMP signaling in osteoblasts is controlled by an ubiquitin-proteasome
      regulatory mechanism involving a cascade of enzymatic reactions. The specificity
      of protein ubiquitination is determined by E3 ubiquitin ligases, which play a
      crucial role in defining substrate specificity and subsequent protein degradation
      by 26S proteasomes. We have examined the role of the E3 ubiquitin ligase Smad
      ubiquitin regulatory factor 1 (Smurf1), a member of the Hect domain family of E3
      ubiquitin ligases in osteoblast function. Smurf1 has been found to interact with
      BMP-activated Smad1 and -5 and to mediate degradation of these Smad proteins.
      Recently we have found that Smurf1 mediates the protein degradation of the
      osteoblast-specific transcription factor Runx2/Cbfa1. To determine the role of
      Smurf1 in osteoblast differentiation, in the present studies we transfected a
      Smurf1 expression plasmid into 2T3 osteoblast precursor cells and found that
      Smurf1 overexpression inhibits BMP signaling and osteoblast differentiation. To
      further investigate the role of Smurf1 in bone formation in vivo, we generated
      transgenic mice in which expression of the epitope-tagged Smurf1 transgene was
      targeted to osteoblasts using the murine 2.3-kb osteoblast-specific type I
      collagen promoter. In these transgenic mice, bone formation was significantly
      reduced during postnatal life. Our results demonstrate for the first time that
      Smurf1 plays a specific role in osteoblast differentiation and bone formation in
      vivo.

PMID- 14701830
TI  - Repression by TTK69 of GAGA-mediated activation occurs in the absence of TTK69
      binding to DNA and solely requires the contribution of the POZ/BTB domain of
      TTK69.
AB  - tramtrack 69 (TTK69) is known to repress GAGA-mediated activation of the eve
      promoter in S2 cells. Here, we show that repression by TTK69 occurs in the
      absence of bona fide TTK69-binding sites on the template, indicating that it does
      not require the binding of TTK69 to DNA. Consistent with this interpretation, the
      POZ/BTB domain of TTK69, which does not bind DNA, is sufficient for repression.
      Moreover, a fusion protein in which the POZ/BTB domain of GAGA is replaced by
      that of TTK69 is not capable of activating the eve promoter but efficiently
      represses GAGA-dependent activation. Repression involves GAGA-TTK69 interaction
      because TTK69 is not capable of repressing basal transcription. Most probably,
      GAGA-TTK69 interaction occurs at the promoter because GAGA.TTK69 complexes are
      fully competent in binding DNA in vitro. Our results also show that repression by
      TTK69 of GAGA-dependent activation of the eve promoter is not mediated by any of
      the co-repressors known to interact with TTK69 (dMi2 or C-terminal binding
      protein) or by trichostatin A-sensitive histone deacetylases. Altogether, these
      observations strongly suggest that the binding of TTK69 prevents the interaction
      of GAGA with the transcription machinery and, therefore, compromises its
      activation potential.

PMID- 14701831
TI  - Dual topology of the Escherichia coli TatA protein.
AB  - The Escherichia coli Tat system has unusual capacity of translocating folded
      proteins across the cytoplasmic membrane. The TatA protein is the most abundant
      known Tat component and consists of a transmembrane segment followed by an
      amphipathic helix and a hydrophilic C terminus. To study the operation mechanism
      of the Tat apparatus, we analyzed the topology of TatA. Intriguingly, alkaline
      phosphatase (PhoA)-positive fusions were obtained at positions Gly-38, Lys-40,
      Asp-51, and Thr-53, which are all located at the cytoplasmic C terminus of the
      TatA protein. Interestingly, replacing phoA with uidA at Thr-53 led to positive
      beta-glucuronidase fusion, implying cytoplasmic location of the TatA C terminus.
      To further determine cellular localization of the TatA C terminus, we deleted the
      phoA gene and left 46 exogenous residues, including the tobacco etch virus (Tev)
      protease cleavage site (Tcs) after Thr-53, yielding TatA(T53)::Tcs. Unlike the
      PhoA and UidA fusions, which abolished the TatA function, the TatA(T53)::Tcs
      construct was able to restore the growth of tatA mutants on the minimal
      trimethlyamine N-oxide media. In vitro and in vivo proteolysis assay showed that
      the Tcs site of TatA(T53)::Tcs was accessible from both the periplasm and
      cytoplasm, indicating a dual topology of the TatA C terminus. Importantly, growth
      conditions seemed to influence the protein level of TatA and the cytoplasmic
      accessibility of the Tcs site of TatA(T53)::Tcs. A function-linked change of the
      TatA topology is suggested, and its implication in protein transport is
      discussed.

PMID- 14701832
TI  - Structural and functional analysis of integrin alpha2I domain interaction with
      echovirus 1.
AB  - Integrins are cell surface receptors for several microbial pathogens including
      echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the
      functional domain (alpha(2)I) of human alpha(2)beta(1) integrin binds to a
      surface depression on the EV1 capsid. This three-dimensional structure of EV1
      bound to alpha(2)I domain provides the first structural details of an integrin
      interacting with a picornavirus. The model indicates that alpha(2)beta(1)
      integrin cannot simultaneously bind both EV1 and the physiological ligand
      collagen. Compared with collagen binding to the alpha(2)I domain, the virus binds
      with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as
      a result of attachment of alpha(2)I. A molecular model, constructed on the basis
      of the EV1-integrin complex, shows that multiple alpha(2)beta(1) heterodimers can
      bind at adjacent sites around the virus 5-fold symmetry axes without steric
      hindrance. In agreement with this, virus attachment to alpha(2)beta(1) integrin
      on the cell surface was found to result in integrin clustering, which can give
      rise to signaling and facilitate the initiation of the viral entry process that
      takes place via caveolae-mediated endocytosis.

PMID- 14701833
TI  - Temporal association of protamine 1 with the inner nuclear membrane protein lamin
      B receptor during spermiogenesis.
AB  - During mammalian spermiogenesis, histones are replaced by transition proteins,
      which are in turn replaced by protamines P1 and P2. P1 protamine contains a short
      arginine/serine-rich (RS) domain that is highly phosphorylated before being
      deposited into sperm chromatin and almost completely dephosphorylated during
      sperm maturation. We now demonstrate that, in elongating spermatids, this
      phosphorylation is required for the temporal association of P1 protamine with
      lamin B receptor (LBR), an inner nuclear membrane protein that also possesses a
      stretch of RS dipeptides at its nucleoplasmic NH(2)-terminal domain. Previous
      studies have shown that the cellular protein p32 also binds tightly to the
      unmodified RS domain of LBR. Extending those findings, we now present evidence
      that p32 prevents phosphorylation of LBR and furthermore that dissociation of
      this protein precedes P1 protamine association. Our data suggest that docking of
      protamine 1 to the nuclear envelope is an important intermediate step in
      spermiogenesis and reveal a novel role for SR protein kinases and p32.

PMID- 14701834
TI  - Electrophysiological characterization of the human Na(+)/nucleoside cotransporter
      1 (hCNT1) and role of adenosine on hCNT1 function.
AB  - We previously reported that the human Na(+)/nucleoside transporter pyrimidine
      preferring 1 (hCNT1) is electrogenic and transports gemcitabine and 5'-deoxy-5
      fluorouridine, a precursor of the active drug 5-fluorouracil. Nevertheless, a
      complete electrophysiological characterization of the basic properties of hCNT1
      mediated translocation has not been performed yet, and the exact role of
      adenosine in hCNT1 function has not been addressed either. In the present work we
      have used the two-electrode voltage clamp technique to investigate hCNT1
      transport mechanism and study the kinetic properties of adenosine as an inhibitor
      of hCNT1. We show that hCNT1 exhibits presteady-state currents that disappear
      upon the addition of adenosine or uridine. Adenosine, a purine nucleoside
      described as a substrate of the pyrimidine-preferring transporters, is not a
      substrate of hCNT1 but a high affinity blocker able to inhibit uridine-induced
      inward currents, the Na(+)-leak currents, and the presteady-state currents, with
      a K(i) of 6.5 microM. The kinetic parameters for uridine, gemcitabine, and 5'
      deoxy-5-fluorouridine were studied as a function of membrane potential; at -50
      mV, K(0.5) was 37, 18, and 245 microM, respectively, and remained voltage
      independent. I(max) for gemcitabine was voltage-independent and accounts for
      approximately 40% that for uridine at -50 mV. Maximal current for 5'-DFUR was
      voltage-dependent and was approximately 150% that for uridine at all membrane
      potentials. K(0.5)(Na(+)) for Na(+) was voltage-independent at hyperpolarized
      membrane potentials (1.2 mM at -50 mV), whereas I(max)(Na(+)) was voltage
      dependent, increasing 2-fold from -50 to -150 mV. Direct measurements of (3)H
      nucleoside or (22)Na fluxes with the charge-associated revealed a ratio of two
      positive inward charges per nucleoside and one Na(+) per positive inward charge,
      suggesting a stoichiometry of two Na(+)/nucleoside.

PMID- 14701835
TI  - Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS
      1 in response to endoplasmic reticulum stress.
AB  - Misfolding of proteins during endoplasmic reticulum (ER) stress results in the
      formation of cytotoxic aggregates. The ER-associated degradation pathway
      counteracts such aggregation through the elimination of misfolded proteins by the
      ubiquitin-proteasome system. We now show that SHP substrate-1 (SHPS-1), a
      transmembrane glycoprotein that regulates cytoskeletal reorganization and cell
      cell communication, is a physiological substrate for the Skp1-Cullin1-NFB42-Rbx1
      (SCF(NFB42)) E3 ubiquitin ligase, a proposed mediator of ER-associated
      degradation. SCF(NFB42) mediated the polyubiquitination of immature SHPS-1 and
      its degradation by the proteasome. Ectopic expression of NFB42 both suppressed
      the formation of aggresome-like structures and the phosphorylation of the
      translational regulator eIF2alpha induced by overproduction of SHPS-1 as well as
      increased the amount of mature SHPS-1 at the cell surface. An NFB42 mutant
      lacking the F box domain had no such effects. Our results suggest that SCF(NFB42)
      regulates SHPS-1 biosynthesis in response to ER stress.

PMID- 14701836
TI  - Aquaporin-1, nothing but a water channel.
AB  - Aquaporin-1 (AQP1) is a membrane channel that allows rapid water movement driven
      by a transmembrane osmotic gradient. It was claimed to have a secondary function
      as a cyclic nucleotide-gated ion channel. However, upon reconstitution into
      planar bilayers, the ion channel exhibited a 10-fold lower single channel
      conductance than in Xenopus oocytes and a 100-fold lower open probability (<10(
      6)) of doubtful physiological significance (Saparov, S. M., Kozono, D., Rothe,
      U., Agre, P., and Pohl, P. (2001) J. Biol. Chem. 276, 31515-31520). Investigating
      AQP1 expressed in human embryonic kidney cells, we now have shown that the
      discrepancy is not due to alterations of AQP1 properties upon reconstitution into
      bilayers but rather to regulatory processes of the oocyte expression system that
      may have been misinterpreted as AQP1 ion channel activity. As confirmed by laser
      scanning reflection microscopy, from 0.8 to 1.4 x 10(6) AQP1 copies/cell
      contributed to osmotic cell swelling. The proper plasma membrane localization was
      confirmed by observing the fluorescence of the N-terminal yellow fluorescent
      protein tag. Whole-cell patch clamp experiments of wild type or tagged AQP1
      expressing cells revealed that neither cGMP nor cAMP mediated ion channel
      activity. The lack of significant CNG ion channel activity rules out a secondary
      role of AQP1 water channels in cellular signal transduction.

PMID- 14701837
TI  - Inhibition of proteasomal function by curcumin induces apoptosis through
      mitochondrial pathway.
AB  - Curcumin is a natural polyphenolic compound having an antiproliferative property,
      which recent evidence suggests is due to its ability to induce apoptosis.
      However, the molecular mechanisms through which curcumin induces apoptosis are
      not fully understood. Here, we report that the curcumin-induced apoptosis is
      mediated through the impairment of the ubiquitin-proteasome system. Exposure of
      curcumin to the mouse neuro 2a cells causes a dose-dependent decrease in
      proteasome activity and an increase in ubiquitinated proteins. Curcumin exposure
      also decreases the turnover of the destabilized enhanced green fluorescence
      protein, a model substrate for proteasome and cellular p53 protein. Like other
      proteasome inhibitors, curcumin targets proliferative cells more efficiently than
      differentiated cells and induces apoptosis via mitochondrial pathways. Addition
      of curcumin to neuro 2a cells induces a rapid decrease in mitochondrial membrane
      potential and the release of cytochrome c into cytosol, followed by activation of
      caspase-9 and caspase-3.

PMID- 14701838
TI  - Role of the POZ zinc finger transcription factor FBI-1 in human and murine
      adipogenesis.
AB  - Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been
      shown to play a role in the control of growth arrest and differentiation in
      several types of mesenchymal cells but not, as yet, adipocytes. We found that a
      POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1),
      was induced during both murine and human preadipocyte differentiation with
      maximal expression levels seen at days 2-4. FBI-1 mRNA was expressed in human
      adipose tissue with the highest levels found in samples from morbidly obese
      subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for
      accelerated adipogenesis with earlier induction of markers of differentiation and
      enhanced lipid accumulation, suggesting that FBI-1 may be an active participant
      in the differentiation process. Consistent with the properties of this family of
      proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed
      reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase
      2, and p107, proteins known to be involved in the regulation of mitotic clonal
      expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin
      A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced
      during the early phases of human and murine preadipocyte differentiation where it
      may contribute to adipogenesis through influencing the switch from cellular
      proliferation to terminal differentiation.

PMID- 14701839
TI  - Identification and characterization of a phosphoinositide phosphate kinase
      homolog.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) plays a central role in
      regulating the actin cytoskeleton as a substrate for phosphoinositide 3-kinase
      and phospholipase C as well as by binding directly to proteins that control the
      processes of actin monomer sequestration, filament severing, capping, nucleation,
      cross-linking, and bundling (Ma, L., Cantley, L. C., Janmey, P. A., and
      Kirschner, M. W. (1998) J. Cell Biol. 140, 1125-1136; Hinchliffe, K. (2000) Curr.
      Biol. 10, R104-R1051). Three related phosphatidylinositol 4-phosphate 5-kinases
      (PI(4)P 5-kinases) have been identified in mammalian cells (types Ialpha, Ibeta,
      and Igamma) and appear to play distinct roles in actin remodeling. Here we have
      identified a fourth member of this family by searching the human genome and EST
      data bases. This new protein, which we have designated phosphatidylinositol
      phosphate kinase homolog (PIPKH), is expressed at relatively high levels in brain
      and testis. Immunoprecipitates of PIPKH expressed in mammalian cells contain
      PI(4)P 5-kinase activity, but this activity is not affected by mutations in
      residues that inactivate other type I PI(4)P 5-kinases. We show that the PI(4)P 5
      kinase activity in PIPKH immunoprecipitates can be explained by the ability of
      PIPKH to heterodimerize with other type I PI(4)P 5-kinases. Transfection of 293t
      cells with PIPKH resulted in >8-fold increase in total phosphatidylinositol 3,4,5
      trisphosphate (PI(3,4,5)P(3)) without a significant net increase in total
      PI(4,5)P(2). When coexpressed with PIPKH, green fluorescent protein (GFP) fusion
      construct of the pleckstrin homology domain from Bruton's tyrosine kinase (GFP
      BTK-PH) localized in intracellular vesicular structures, suggesting an unusual
      intracellular site of PI(3,4,5)P(3) production. Finally, expression of PIPKH
      induced the reorganization of actin from predominantly stress fibers to
      predominantly foci and comets similar to those observed previously in cells
      infected with the intracellular pathogen Listeria or transfected with recombinant
      PIPKIalpha. These results suggest that PIPKH acts as a scaffold to localize and
      regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P(3).

PMID- 14701840
TI  - The A-superfamily of conotoxins: structural and functional divergence.
AB  - The generation of functional novelty in proteins encoded by a gene superfamily is
      seldom well documented. In this report, we define the A-conotoxin superfamily,
      which is widely expressed in venoms of the predatory cone snails (Conus), and
      show how gene products that diverge considerably in structure and function have
      arisen within the same superfamily. A cDNA clone encoding alpha-conotoxin GI, the
      first conotoxin characterized, provided initial data that identified the A
      superfamily. Conotoxin precursors in the A-superfamily were identified from six
      Conus species: most (11/16) encoded alpha-conotoxins, but some (5/16) belong to a
      family of excitatory peptides, the kappaA-conotoxins that target voltage-gated
      ion channels. alpha-Conotoxins are two-disulfide-bridged nicotinic antagonists,
      13-19 amino acids in length; kappaA-conotoxins are larger (31-36 amino acids)
      with three disulfide bridges. Purification and biochemical characterization of
      one peptide, kappaA-conotoxin MIVA is reported; five of the other predicted
      conotoxins were previously venom-purified. A comparative analysis of conotoxins
      purified from venom, and their precursors reveal novel post-translational
      processing, as well as mutational events leading to polymorphism. Patterns of
      sequence divergence and Cys codon usage define the major superfamily branches and
      suggest how these separate branches arose.

PMID- 14701841
TI  - Structural characterization of TSC-36/Flik: analysis of two charge isoforms.
AB  - Recombinant forms of the glycoprotein TSC-36/Flik were expressed in human cells
      and used to compare their structural and functional properties with those
      described for other members of the BM-40/SPARC/osteonectin protein family. TSC-36
      was found to occur in two charge isoforms that differ in the extent of
      sialylation of otherwise identical N-linked, complex type oligosaccharides.
      Conformational analysis with both circular dichroism and intrinsic fluorescence
      spectroscopy showed a lack of significant structural changes upon calcium
      addition or depletion. This finding is in contrast to results obtained for
      several other BM-40 family members and indicates that the extracellular calcium
      binding domain in TSC-36 is non-functional. The lack of conservation of important
      functional features common to several other members of the BM-40 family indicates
      that TSC-36, despite its sequence homology to BM-40, has evolved clearly distinct
      properties.

PMID- 14701842
TI  - Probing the role of metal ions in the catalysis of Helicobacter pylori 3-deoxy-D
      manno-octulosonate-8-phosphate synthase using a transient kinetic analysis.
AB  - 3-Deoxy-d-manno-2-octulosonate-8-phosphate (KDO8P) synthase catalyzes the net
      condensation of phosphoenolpyruvate and d-arabinose 5-phosphate to form KDO8P and
      inorganic phosphate (Pi). Two classes of KDO8P synthases have been identified.
      The Class I KDO8P synthases (e.g. Escherchia coli KDO8P synthase) catalyze the
      condensation reaction in a metal-independent fashion, whereas the Class II
      enzymes (e.g. Aquifex aeolicus) require metal ions for catalysis. Helicobacter
      pylori (H. pylori) KDO8P synthase, a Zn2+-dependent metalloenzyme, has recently
      been found to be a Class II enzyme and has a high degree of clinical significance
      since it is an attractive molecular target for the design of novel antibiotic
      therapy. Although the presence of a divalent metal ion in Class II KDO8P
      synthases is essential for catalysis, there is a paucity of mechanistic
      information on the role of the metal ions and functional differences as compared
      with Class I enzymes. Using H. pylori KDO8P synthase as a prototypical Class II
      enzyme, a steady-state and transient kinetic approach was undertaken to
      understand the role of the metal ion in catalysis and define the kinetic reaction
      pathway. Metal reconstitution experiments examining the reaction kinetics using
      Zn2+, Cd2+, Cu2+, Co2+, Mn2+, and Ni2+ yielded surprising results in that the
      Cd2+ enzyme has the greatest activity. Unlike Class-I KDO8P synthases, the Class
      II metallo-KDO8P synthases containing Zn2+, Cd2+, Cu2+, and Co2+ show
      cooperativity. This study presents the first detailed kinetic characterization of
      a metal-dependent Class II KDO8P synthase and offers mechanistic insight for how
      the divalent metal ions modulate catalysis through effects on chemistry as well
      as quaternary protein structure.

PMID- 14701843
TI  - Molecular fingerprinting of carbohydrate structure phenotypes of three porifera
      proteoglycan-like glyconectins.
AB  - Glyconectins (GNs) represent a new class of proteoglycan-like cell adhesion and
      recognition molecules found in several Porifera species. Physico-chemical
      properties of GN carbohydrate moieties, such as size, composition, and resistance
      to most glycosaminoglycan-degrading enzymes, distinguish them from any other type
      of known glycoproteins. The molecular mechanism of GN-mediated self/non-self
      discrimination function is based on highly species-specific and Ca(2+)-dependent
      GN to GN associations that approach the selectivity of the evolutionarily
      advanced immunoglobulin superfamily. Carbohydrates of glyconectins 1, 2, and 3
      are essential for species-specific auto-aggregation properties in three
      respective Porifera species. To obtain a structural insight into the molecular
      mechanisms, we performed carbohydrate structural analyses of glyconectins
      isolated from the three sponge model systems, Microciona prolifera (GN1),
      Halichondria panicea (GN2), and Cliona celata (GN3). The glycan content of all
      three GNs ranged between 40 and 60% of their total mass. Our approach using
      sequential and selective chemical degradation of GN glycans and subsequent mass
      spectrometric and NMR analyses revealed that each glyconectin presents novel and
      highly species-specific carbohydrate sequences. All three GNs include distinct
      acid-resistant and acid-labile carbohydrate domains, the latter composed of novel
      repetitive units. We have sequenced four short sulfated and one pyruvilated unit
      in GN1, eight larger and branched pyruvilated oligosaccharides in GN2, which
      represent a heterogeneous but related family of structures, and four sulfated
      units in GN3.

PMID- 14701844
TI  - Molecular recognition between glyconectins as an adhesion self-assembly pathway
      to multicellularity.
AB  - The appearance of multicellular forms of life has been tightly coupled to the
      ability of an organism to retain its own anatomical integrity and to distinguish
      self from non-self. Large glycoconjugates, which make up the outermost cell
      surface layer of all Metazoans, are the primary candidates for the primordial
      adhesion and recognition functions in biological self-assembly systems. Atomic
      force microscopy experiments demonstrated that the binding strength between a
      single pair of Porifera cell surface glyconectin 1 glycoconjugates from
      Microciona prolifera can hold the weight of 1600 cells, proving their adhesion
      functions. Here, measurement of molecular self-recognition of glyconectins (GNs)
      purified from three Porifera species was used as an experimental model for
      primordial xenogeneic self/non-self discrimination. Physicochemical and
      biochemical characterization of the three glyconectins, their glycans, and
      peptides using gel electrophoresis, ultracentrifugation, NMR, mass spectrometry,
      glycosaminoglycan-degrading enzyme treatment, amino acid and carbohydrate
      analyses, and peptide mapping showed that GNs define a new family of proteoglycan
      like molecules exhibiting species-specific structures with complex and repetitive
      acidic carbohydrate motives different from the classical proteoglycans and
      mucins. In functional self-assembly color-coded bead, cell, and blotting assays,
      glyconectins displayed species-specific recognition and adhesion. Affinity
      purified monospecific polyclonal antibodies prepared against GN1, -2, and -3
      glycans selectively inhibited cell adhesion of the respective sponge species.
      These results together with species-specific coaggregation of GN carbohydrate
      coated beads with cells showed that GN glycans are functional in cell recognition
      and adhesion. The specificity of carbohydrate-mediated homophilic GN interactions
      in Porifera approaches the binding selectivity of the evolutionarily advanced
      immunoglobulin superfamily. Xenoselectivity of primordial glyconectin to
      glyconectin recognition may be a new paradigm in the self-assembly and non-self
      discrimination pathway of cellular adhesion leading to multicellularity.

PMID- 14701845
TI  - Identification of a conserved sequence motif that promotes Cdc37 and cyclin D1
      binding to Cdk4.
AB  - Cdc37 is a molecular chaperone that is important for the stability and activity
      of several protein kinases, including Cdk4 and Raf1. We first determined, using
      in vitro assays, that Cdc37 binds to the amino-terminal lobe of Cdk4. Subsequent
      mutagenesis revealed that Gly-15 (G15A) and Gly-18 (G18A) were critical for Cdc37
      Cdk4 complex formation. Gly-15 and Gly-18 of Cdk4 are within the conserved Gly-X
      Gly-X-X-Gly motif that is required for ATP binding to the kinase. Mutation of
      either glycine at the equivalent positions of Raf1 (G358A and G361A) also
      inhibited Cdc37 binding to Raf1. Replacing another conserved residue critical for
      ATP binding and kinase activity, Lys-35 (K35A), reduced Cdc37-Cdk4 complex
      formation but to a lesser extent. The interaction of Cdk4 with Cdc37 in vitro was
      not sensitive to changes in ATP levels. Cell-based assays indicated that
      Cdk4(G15A) and Cdk4(G18A) were present at the same level as wild type Cdk4.
      Equivalent amounts of p16 bound to Cdk4(G15A) and Cdk4(G18A) relative to wild
      type Cdk4, suggesting that Cdk4(G15A) and Cdk4(G18A) adopt significant tertiary
      structure. However, in contrast to wild type Cdk4, Cdk4(G15A), and Cdk4(G18A) had
      greatly reduced binding of cyclin D1, Cdc37, and Hsp90. Importantly,
      overexpression of Cdc37 not only stimulated cyclin D1 binding to wild type Cdk4
      but also restored its binding to Cdk4(G15A). Under the same conditions, p16
      binding to wild type Cdk4 was suppressed. Our findings show that the interaction
      of Cdc37 with its client protein kinases requires amino acid residues within a
      motif that is present in many protein kinases.

PMID- 14701847
TI  - Redesigning the folding energetics of a model three-helix bundle protein by site
      directed mutagenesis.
AB  - Because of their limited size and complexity, de novo designed proteins are
      particularly useful for the detailed investigation of folding thermodynamics and
      mechanisms. Here, we describe how subtle changes in the hydrophobic core of a
      model three-helix bundle protein (GM-0) alter its folding energetics. To explore
      the folding tolerance of GM-0 toward amino acid sequence variability, two mutant
      proteins (GM-1 and GM-2) were generated. In the mutants, cavities were created in
      the hydrophobic core of the protein by either singly (GM-1; L35A variant) or
      doubly (GM-2; L35A/I39A variant) replacing large hydrophobic side chains by
      smaller Ala residues. The folding of GM-0 is characterized by two partially
      folded intermediate states exhibiting characteristics of molten globules, as
      evidenced by pressure-unfolding and pressure-assisted cold denaturation
      experiments. In contrast, the folding energetics of both mutants, GM-1 and GM-2,
      exhibit only one folding intermediate. Our results support the view that simple
      but biologically important folding motifs such as the three-helix bundle can
      reveal complex folding plasticity, and they point to the role of hydrophobic
      packing as a determinant of the overall stability and folding thermodynamic of
      the helix bundle.

PMID- 14701846
TI  - Fibrillogenesis and cytotoxic activity of the amyloid-forming apomyoglobin mutant
      W7FW14F.
AB  - The apomyoglobin mutant W7FW14F forms amyloid-like fibrils at physiological pH.
      We examined the kinetics of fibrillogenesis using three techniques: the time
      dependence of the fluorescence emission of thioflavin T and 1-anilino-8
      naphthalenesulfonate, circular dichroism measurements, and electron microscopy.
      We found that in the early stage of fibril formation, non-native apomyoglobin
      molecules containing beta-structure elements aggregate to form a nucleus.
      Subsequently, more molecules aggregate around the nucleus, thereby resulting in
      fibril elongation. We evaluated by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) the cytotoxicity of these aggregates at the early
      stage of fibril elongation versus mature fibrils and the wild-type protein.
      Similar to other amyloid-forming proteins, cell toxicity was not due to insoluble
      mature fibrils but rather to early pre-fibrillar aggregates. Propidium iodide
      uptake showed that cell toxicity is the result of altered membrane permeability.
      Phalloidin staining showed that membrane damage is not associated to an altered
      cell shape caused by changes in the cytoskeleton.

PMID- 14701848
TI  - Acetylation of the BETA2 transcription factor by p300-associated factor is
      important in insulin gene expression.
AB  - The BETA2 transcription factor influences islet beta cell development and
      function. Activation of insulin gene transcription by this member of the basic
      helix-loop-helix gene family is mediated by p300 through the ability of this
      coactivator to form a functional bridge between the basal transcriptional
      apparatus, BETA2, and PDX-1, another key transcription factor. In this report, we
      examined whether BETA2-mediated stimulation was also directly influenced by the
      acetyltransferase activities of p300 or the p300-associated factor. BETA2 was
      specifically and selectively acetylated by p300-associated factor in beta cells.
      Sites of BETA2 acetylation were found within the loop region of the basic helix
      loop-helix DNA binding/dimerization domain and a more C-terminal region involved
      in activation. Insulin gene transcription was decreased by blocking acetylation
      of BETA2 because of effects on DNA binding and activation potential. These
      findings suggest that acetylation of BETA2 plays a role in controlling the
      activation state of this islet regulatory factor.

PMID- 14701849
TI  - Mitochondrial pH monitored by a new engineered green fluorescent protein mutant.
AB  - We here describe a new molecularly engineered green fluorescent protein chimera
      that shows a high sensitivity to pH in the alkaline range. This probe was named
      mtAlpHi, for mitochondrial alkaline pH indicator, and possesses several key
      properties that render it optimal for studying the dynamics of mitochondrial
      matrix pH, e.g. it has an apparent pK(a) (pK(a)') around 8.5, it shows reversible
      and large changes in fluorescence in response to changes in pH (both in vitro and
      in intact cells), and it is selectively targeted to the mitochondrial matrix.
      Using mtAlpHi we could monitor pH changes that occur in the mitochondrial matrix
      in a variety of situations, e.g. treatment with uncouplers or Ca(2+) ionophores,
      addition of drugs that interfere with ATP synthesis or electron flow in the
      respiratory chain, weak bases or acids, and receptor activation. We observed
      heterogeneous pH increases in the mitochondrial matrix during Ca(2+) accumulation
      by this organelle. Finally, we demonstrate that Ca(2+) mobilization from internal
      stores induced by ionomycin and A23187 cause a dramatic acidification of the
      mitochondrial matrix.

PMID- 14701850
TI  - Phosphorylation and stabilization of ATP binding cassette transporter A1 by
      synthetic amphiphilic helical peptides.
AB  - To investigate structural requirement of helical apolipoprotein to phosphorylate
      and stabilize ATP-binding cassette transporter A1 (ABCA1), synthetic peptides
      (Remaley, A. T., Thomas, F., Stonik, J. A., Demosky, S. J., Bark, S. E., Neufeld,
      E. B., Bocharov, A. V., Vishnyakova, T. G., Patterson, A. P., Eggerman, T. L.,
      Santamarina-Fojo, S., and Brewer, H. B. (2003) J. Lipid Res. 44, 828-836) were
      examined for these activities. L37pA, an L amino acid peptide that contains two
      class-A amphiphilic helices, and D37pA, the same peptide with all D amino acids,
      both removed cholesterol and phospholipid from differentiated THP-1 cells more
      than apolipoproteins (apos) A-I, A-II, and E. Both peptides also mediated lipid
      release from human fibroblasts WI-38 similar to apoA-I. L2D37pA, an L-peptide
      whose valine and tyrosine were replaced with D amino acids also promoted lipid
      release from WI-38 but less so with THP-1, whereas L3D37pA, in which alanine,
      lysine, and asparatic acid were replaced with D amino acids was ineffective in
      lipid release for both cell lines. ABCA1 protein in THP-1 and WT-38 was
      stabilized against proteolytic degradation by apoA-I, apoA-II, and apoE and by
      all the peptides tested except for L3D37pA, and ABCA1 phosphorylation closely
      correlated with its stabilization. The analysis of the relationship among these
      parameters indicated that removal of phospholipid triggers signals for
      phosphorylation and stabilization of ABCA1. We thus concluded that an amphiphilic
      helical motif is the minimum structural requirement for a protein to stabilize
      ABCA1 against proteolytic degradation.

PMID- 14701851
TI  - Extracellular histidine residues crucial for Na+ self-inhibition of epithelial
      Na+ channels.
AB  - Epithelial Na(+) channels (ENaC) participate in the regulation of extracellular
      fluid volume homeostasis and blood pressure. Channel activity is regulated by
      both extracellular and intracellular Na(+). The down-regulation of ENaC activity
      by external Na(+) is referred to as Na(+) self-inhibition. We investigated the
      structural determinants of Na(+) self-inhibition by expressing wild-type or
      mutant ENaCs in Xenopus oocytes and analyzing changes in whole-cell Na(+)
      currents following a rapid increase of bath Na(+) concentration. Our results
      indicated that wild-type mouse alphabetagammaENaC has intrinsic Na(+) self
      inhibition similar to that reported for human, rat, and Xenopus ENaCs. Mutations
      at His(239) (gammaH239R, gammaH239D, and gammaH239C) in the extracellular loop of
      the gammaENaC subunit prevented Na(+) self-inhibition whereas mutations of the
      corresponding His(282) in alphaENaC (alphaH282D, alphaH282R, alphaH282W, and
      alphaH282C) significantly enhanced Na(+) self-inhibition. These results suggest
      that these two histidine residues within the extracellular loops are crucial
      structural determinants for Na(+) self-inhibition.

PMID- 14701852
TI  - Regulation of Xenopus Aurora A activation by TPX2.
AB  - The oncogenic protein kinase Aurora A is a critical regulator of meiotic and
      mitotic cell cycles in eukaryotic cells. Aurora A autoactivation by
      autophosphorylation is promoted by specific non-catalytic binding proteins. One
      such protein is TPX2, a required spindle assembly factor in higher eukaryotes
      whose ability to activate Aurora A by direct binding to the kinase catalytic
      domain has been established by biochemical and structural analysis. In this
      report we clarify the autoactivation mechanism of Aurora A by demonstrating that
      of seven amino acids which become autophosphorylated by Aurora A, only Thr-295 is
      required for activity. Association of Aurora A with TPX2 leads to activation of
      the kinase, in parallel with phosphorylation of TPX2. We identify the sites as
      three Ser residues in the N terminus of TPX2; however, mutation of these residues
      does not affect Aurora A activation by TPX2. In contrast, the mutation of a
      putative Aurora A-binding motif in TPX2 abolishes both phosphorylation of TPX2
      and activation of Aurora A. We have also investigated the interaction between
      Xenopus p53 and Xenopus Aurora A. p53 blocks the activity of either full-length
      Aurora A or the isolated catalytic domain. Interestingly, inhibition is blocked
      by TPX2, suggesting that the ability of Aurora A to transform cells could be
      regulated by p53, TPX2, or other binding proteins.

PMID- 14701853
TI  - Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta
      glucuronides.
AB  - klotho mutant mice provide a unique model to analyze mechanisms of aging because
      their phenotypes resemble those of human aging-associated disorders. The klotho
      gene encodes Klotho, a type I membrane protein that shares sequence similarity
      with members of the glycosidase family 1. Because Klotho lacks the glutamic acid
      residues that have been shown to be involved in the catalytic activity of this
      family of enzymes, the function of this protein was unknown. Here, we have
      studied the biochemical characteristics of recombinant Klotho. The purified
      chimeric Klotho-human IgG1 Fc protein (KLFc) was assayed with a series of 4
      methylumbelliferyl (4Mu) beta-glycosides as potential substrates. An enzymatic
      activity of Klotho was observed only with 4-methylumbelliferyl beta-D-glucuronide
      in contrast to bovine liver beta-glucuronidase, which exhibits a rather wide
      substrate specificity. Furthermore, the enzymatic activity of KLFc was reduced by
      the addition of specific inhibitors of beta-glucuronidase. A number of natural
      beta-glucuronides were screened by competitive inhibition for KLFc beta
      glucuronidase. We found that steroid beta-glucuronides such as beta-estradiol 3
      beta-D-glucuronide, estrone 3-beta-D-glucuronide, and estriol 3beta-D-glucuronide
      were hydrolyzed by KLFc. The artificial fluorescent substrate and the steroid
      conjugates share a common phenolic structure. Collectively, these data suggest
      that Klotho functions as a novel beta-glucuronidase and that steroid beta
      glucuronides are potential candidates for the natural substrate(s) of Klotho.

PMID- 14701854
TI  - Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling
      pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases.
AB  - Epidermal growth factor receptor (EGFR) activation is absolutely required for
      cervical cell proliferation. This suggests that EGFR-inhibitory agents may be of
      therapeutic value. In the present study, we investigated the effects of
      epigallocatechin-3-gallate (EGCG), a bioactive green tea polyphenol, on EGFR
      signaling in cervical cells. EGCG inhibits epidermal growth factor-dependent
      activation of EGFR, and EGFR-dependent activation of the mitogen-activated
      protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG
      dependent reduction in ERK and AKT activity is associated with reduced
      phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These
      changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels,
      reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these
      findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase
      mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest.
      Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to
      inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits
      ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to
      inhibit EGF-dependent signaling. Importantly, the EGCG inhibition is selective,
      as EGCG does not effect the EGFR-dependent activation of JNK. These results
      suggest that EGCG acts to selectively inhibit multiple EGF-dependent kinases to
      inhibit cell proliferation.

PMID- 14701855
TI  - Lipoic acid protects efficiently only against a specific form of peroxynitrite
      induced damage.
AB  - The ability of the sulfur-containing compounds glutathione (GSH), glutathione
      disulphide (GSSG), S-methylglutathione (GSMe), lipoic acid (LA), and
      dihydrolipoic acid (DHLA) to protect against hypochlorous acid (HOCl)-mediated
      damage and peroxynitrite (ONOOH)-induced damage has been compared. Protective
      activity was assessed in competition assays by monitoring several detectors, i.e.
      dihydrorhodamine-123 (DHR-123) oxidation, alpha(1)-antiproteinase (alpha(1)-AP)
      inactivation, and glutathione S-transferase P1-1 (GST-P1-1) inactivation. In
      addition, nitration of tyrosine was measured to assess protection of the sulfur
      containing compounds against ONOOH. For protection against HOCl, the efficacy of
      the antioxidant was controlled by the ratio of the reaction rates of the
      antioxidant and the detector molecule with the oxidant. The rank order of the
      activity of the antioxidants (GSH > DHLA approximately LA approximately GSMe >
      GSSG) appeared to be independent of the detector used. However, the rank order of
      the antioxidants against ONOOH-induced damage is strongly dependent on the
      detector. LA was 40 times less active than GSH in the inhibition of ONOOH-induced
      DHR-123 oxidation, whereas LA was 20 times more active than GSH in preventing the
      inhibition of GST-P1-1 by ONOOH. This points to different molecular mechanisms of
      ONOOH damage to DHR-123 compared with ONOOH damage to GST-P1-1. LA is a poor
      antioxidant in protecting against the form of ONOOH damage involved in DHR-123
      oxidation. In the form of ONOOH toxicity involved in GST-P1-1 inhibition, LA is
      the most potent sulfur-containing antioxidant in our series. It is proposed that
      an intermediate product in which both sulfur atoms of LA have reacted is involved
      in the reaction of ONOOH with LA. The high potency of LA to protect GST-P1-1
      against ONOOH might be of therapeutic interest.

PMID- 14701856
TI  - Transcription factors and nuclear receptors interact with the SWI/SNF complex
      through the BAF60c subunit.
AB  - Transcriptional activity relies on coregulators that modify chromatin structure
      or serve as bridging factors between transcription factors and the basal
      transcription machinery. We identified a new coregulator of peroxisome
      proliferator-activated receptor gamma, BRG1/Brm-associated factor of 60 kDa,
      subunit c2 (BAF60c2), in a yeast two-hybrid screen of a human adipose tissue cDNA
      library. BAF60c2 represents a new isoform of BAF60c, a component of the SWI/SNF
      (mating type switching/sucrose non-fermenting) chromatin remodeling complex. This
      new isoform as well as the previously identified protein, renamed BAF60c1, is
      localized primarily in the cell nucleus and is expressed in a wide variety of
      tissues. Both BAF60c isoforms bind to several nuclear receptors and transcription
      factors of various families. BAF60c proteins interact in a ligand-independent
      manner with peroxisome proliferator-activated receptor gamma and enhance its
      transcriptional activity. Both isoforms are enriched in the central nervous
      system and also modulate the transcriptional activity of retinoic acid-related
      orphan receptor alpha1. In conclusion, BAF60c represents a new coregulator that
      constitutes an important anchoring point by which the SWI/SNF complex is
      recruited to nuclear receptors and other transcription factors.

PMID- 14701857
TI  - Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing
      pathway are distinct from those of its prolyl 4-hydroxylases.
AB  - The activity of hypoxia-inducible transcription factor HIF, an alphabeta
      heterodimer that has an essential role in adaptation to low oxygen availability,
      is regulated by two oxygen-dependent hydroxylation events. Hydroxylation of
      specific proline residues by HIF prolyl 4-hydroxylases targets the HIF-alpha
      subunit for proteasomal destruction, whereas hydroxylation of an asparagine in
      the C-terminal transactivation domain prevents its interaction with the
      transcriptional coactivator p300. The HIF asparaginyl hydroxylase is identical to
      a previously known factor inhibiting HIF (FIH). We report here that recombinant
      FIH has unique catalytic and inhibitory properties when compared with those of
      the HIF prolyl 4-hydroxylases. FIH was found to require particularly long peptide
      substrates so that omission of only a few residues from the N or C terminus of a
      35-residue HIF-1alpha sequence markedly reduced its substrate activity.
      Hydroxylation of two HIF-2alpha peptides was far less efficient than that of the
      corresponding HIF-1alpha peptides. The K(m) of FIH for O(2) was about 40% of its
      atmospheric concentration, being about one-third of those of the HIF prolyl 4
      hydroxylases but 2.5 times that of the type I collagen prolyl 4-hydroxylase.
      Several 2-oxoglutarate analogs were found to inhibit FIH but with distinctly
      different potencies from the HIF prolyl 4-hydroxylases. For example, the two most
      potent HIF prolyl 4-hydroxylase inhibitors among the compounds studied were the
      least effective ones for FIH. It should therefore be possible to develop specific
      small molecule inhibitors for the two enzyme classes involved in the hypoxia
      response.

PMID- 14701858
TI  - Rescue of female infertility from the loss of cyclooxygenase-2 by compensatory up
      regulation of cyclooxygenase-1 is a function of genetic makeup.
AB  - Cyclooxygenase-2 (COX-2), an inducible rate-limiting enzyme in prostaglandin
      biosynthesis, is implicated in various physiological and pathological processes
      including female fertility, renal function, angiogenesis, inflammation, and
      tumorigenesis. We showed previously that targeted deletion of Ptgs2 encoding COX
      2, but not Ptgs1 encoding COX-1, in C57BL/6J/129 mice produces complete female
      infertility resulting from multiple reproductive failures spanning ovulation,
      fertilization, and implantation. Here we show that Ptgs2 null mice on a CD1
      background have dramatically improved female fertility including ovulation,
      fertilization, and implantation, giving rise to live births. We provide evidence
      that this improved fertility in CD1 Ptgs2 null mice is the result of a
      compensatory up-regulation of Ptgs1 which does not occur in C57BL/6J/129 mice
      missing Ptgs2. These results clearly demonstrate for the first time that COX-1
      can replace specific functions of COX-2 in vivo in the context of genetic
      disparity. In light of this finding, the therapeutic use and efficacy of COX-2
      specific inhibitors among human populations without regard for genetic and ethnic
      diversities should be revisited.

PMID- 14701859
TI  - Specialized roles of the two pathways for the synthesis of mannosylglycerate in
      osmoadaptation and thermoadaptation of Rhodothermus marinus.
AB  - Rhodothermus marinus responds to fluctuations in the growth temperature and/or
      salinity by accumulating mannosylglycerate (MG). Two alternative pathways for the
      synthesis of MG have been identified in this bacterium: a single-step pathway and
      a two-step pathway. In this work, the genetic and biochemical characterization of
      the two-step pathway was carried out with the goal of understanding the function
      of the two pathways and their regulatory mechanisms. Mannosyl-3-phosphoglycerate
      synthase (MPGS) of the two-step pathway was purified from R. marinus. Sequence
      information led to the isolation of two contiguous genes, mpgs (encoding MPGS)
      and mpgp (encoding mannosyl-3-phosphoglycerate phosphatase). The recombinant MPGS
      had a low specific activity compared with other homologous MPGSs and contained
      approximately 30 additional residues at the C terminus. Truncation of this
      extension produced a protein with a 10-fold higher specific activity. Moreover,
      the activity of the complete MPGS was enhanced upon incubation with R. marinus
      cell extracts, and protease inhibitors abolished activation. Therefore, the C
      terminal peptide of MPGS was identified as a regulatory site for short term
      control of MG synthesis in R. marinus. The control of gene expression by heat and
      osmotic stress was also studied; the level of mannosylglycerate synthase involved
      in the single-step pathway was selectively enhanced by heat stress, whereas MPGS
      was overproduced in response to osmotic stress. The concomitant changes in the
      level of MG were assessed as well. We conclude that the two alternative pathways
      for the synthesis of MG are differently regulated at the level of expression to
      play specific roles in the adaptation of R. marinus to two different types of
      aggression. This is the only example of pathway multiplicity being rationalized
      in terms of the need to respond efficiently to distinct environmental stresses.

PMID- 14701860
TI  - Situational repair of replication forks: roles of RecG and RecA proteins.
AB  - Replication forks often stall or collapse when they encounter a DNA lesion. Fork
      regression is part of several major paths to the repair of stalled forks,
      allowing nonmutagenic bypass of the lesion. We have shown previously that
      Escherichia coli RecA protein can promote extensive regression of a forked DNA
      substrate that mimics a possible structure of a replication fork stalled at a
      leading strand lesion. Using electron microscopy and gel electrophoresis, we
      demonstrate that another protein, E. coli RecG helicase, promotes extensive fork
      regression in the same system. The RecG-catalyzed fork regression is very
      efficient and faster than the RecA-promoted reaction (up to 240 bp s(-1)),
      despite very limited processivity of the RecG protein. The reaction is dependent
      upon ATP hydrolysis and is stimulated by single-stranded binding protein. The
      RecA- and RecG-promoted reactions are not synergistic. In fact, RecG functions
      poorly under the conditions optimal for the RecA reaction, and vice versa. When
      both RecA and RecG proteins are incubated with the DNA substrate, high RecG
      concentrations inhibit the RecA protein-promoted fork regression. The very
      different reaction profiles may reflect a situational application of these
      proteins to the rescue of stalled replication forks in vivo.

PMID- 14701861
TI  - The fusion oncoprotein PML-RARalpha induces endoplasmic reticulum (ER)-associated
      degradation of N-CoR and ER stress.
AB  - PML-RARalpha, a fusion protein of promyelocytic leukemia (PML) and the retinoic
      acid receptor-alpha (RARalpha), causes acute promyelocytic leukemias (APL).
      Although the role of nuclear PML-RARalpha has been extensively studied, a
      significant amount of PML-RARalpha is in the cytoplasm. The role cytoplasmic PML
      RARalpha plays in leukemogenesis is unknown. Here we report that PML-RARalpha
      induces the N-CoR accumulation in the endoplasmic reticulum (ER), leading to the
      induction of ER stress and the processing of activating transcription factor 6
      (ATF6), the unfolded protein response. PML-RARalpha stimulates the ubiquitylation
      of N-CoR via Ubc6 that is involved in the protein quality control. This ER
      associated degradation (ERAD) of N-CoR reduces the soluble N-CoR protein levels
      in the nucleus. The two N-CoR-interacting sites in PML-RARalpha are required for
      the ERAD of N-CoR, suggesting the aberrant binding of PML-RARalpha to N-CoR may
      induce the ERAD of N-CoR. Overexpression of N-CoR induces the differentiation of
      APL-derived NB4 cells, suggesting that the low levels of N-CoR in the nucleus may
      contribute at least partly to PML-RARalpha-mediated leukemogenesis.

PMID- 14701862
TI  - A mutant Stat5b with weaker DNA binding affinity defines a key defective pathway
      in nonobese diabetic mice.
AB  - A number of cytokines that finely regulate immune response have been implicated
      in the pathogenesis or protection of type 1 diabetes and other autoimmune
      diseases. It is, therefore, of pivotal importance to examine a family of proteins
      that serve as signal transducers and activators of transcription (STATs), which
      regulate the transcription of a variety of cytokines. We report here a defective
      gene (Stat5b) located on chromosome 11 within a previously mapped T1D
      susceptibility interval (Idd4) in the nonobese diabetic (NOD) mice. Our
      sequencing analysis revealed a unique mutation C1462A that results in a leucine
      to methionine (L327M) in Stat5b of NOD mice. Leu(327), the first residue in the
      DNA binding domain of STAT proteins, is conserved in all identified mammalian
      STAT proteins. Homology modeling predicted that the mutant Stat5b has a weaker
      DNA binding, which was confirmed by DNA-protein binding assays. The inapt
      transcriptional regulation ability of the mutated Stat5b is proved by decreased
      levels of RNA of Stat5b-regulated genes (IL-2Rbeta and Pim1). Consequently, IL
      2Rbeta and Pim1 proteins were shown by Western blotting to have lower levels in
      NOD compared with normal B6 mice. These proteins have been implicated in immune
      regulation, apoptosis, activation-induced cell death, and control of
      autoimmunity. Therefore, the Stat5b pathway is a key molecular defect in NOD
      mice.

PMID- 14701863
TI  - Notch4 inhibits endothelial apoptosis via RBP-Jkappa-dependent and -independent
      pathways.
AB  - Notch4, a member of the Notch family of transmembrane receptors, is expressed
      primarily on endothelial cells. Activation of Notch in various cell systems has
      been shown to regulate cell fate decisions, partly by regulating the propensity
      of cells to live or die. Various studies have demonstrated a role for Notch1 in
      modulating apoptosis, either in a positive or negative manner. In this study, we
      determined that constitutively active Notch4 (Notch4 intracellular domain)
      inhibited endothelial apoptosis triggered by lipopolysaccharide. Notch signals
      are transmitted by derepression and coactivation of the transcriptional
      repressor, RBP-Jkappa, as well as by less well defined mechanisms that are
      independent of RBP-Jkappa. A Notch mutant lacking the N-terminal RAM domain
      showed only partial antiapoptotic activity relative to Notch4 intracellular
      domain but stimulated equivalent RBP-Jkappa-dependent transcriptional activity.
      Similarly, constitutively active RBP-Jkappa activated a full transcriptional
      response but only demonstrated partial antiapoptotic activity. Additional studies
      suggest that Notch4 provides endothelial protection in two ways: inhibition of
      the JNK-dependent proapoptotic pathway in an RBP-Jkappa-dependent manner and
      induction of an antiapoptotic pathway through an RBP-Jkappa-independent up
      regulation of Bcl-2. Our findings demonstrate that Notch4 activation inhibits
      apoptosis through multiple pathways and provides one mechanism to explain the
      remarkable capacity of endothelial cells to withstand apoptosis.

PMID- 14701864
TI  - ADAMTS4 (aggrecanase-1) activation on the cell surface involves C-terminal
      cleavage by glycosylphosphatidyl inositol-anchored membrane type 4-matrix
      metalloproteinase and binding of the activated proteinase to chondroitin sulfate
      and heparan sulfate on syndecan-1.
AB  - C-terminal truncation of ADAMTS-4 from the p68 form to the p53 form is required
      for activation of its capacity to cleave the Glu(373)-Ala(374) interglobular
      domain bond of aggrecan. In transfected human chondrosarcoma cells, this process
      is not autoproteolytic because the same products form with an inactive mutant of
      ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin-like motif 4)
      and truncation is completely blocked by tissue inhibitor of metalloproteinase-1.
      Instead, activation can be mediated by glycosylphosphatidyl inositol-anchored
      membrane type 4-matrix metalloproteinase (MT4-MMP, MMP-17) because co
      transfection with the active form of MT4-MMP markedly enhanced activation,
      whereas an inactive mutant of MT4-MMP was ineffective. Treatment of co
      transfected cells with phosphatidylinositol-specific phospholipase C liberated
      the complex of MT4-MMP and p68 ADAMTS4 from the cell membrane, but the p53
      ADAMTS4 remained associated. Specific glycosaminoglycan lyase digestions,
      followed by product analyses using fluorescence-assisted carbohydrate
      electrophoresis and immunoprecipitation experiments, showed that the p53 form is
      associated with syndecan-1 through both chondroitin sulfate and heparan sulfate.
      We conclude that ADAMTS-4 activation in this cell system involves the coordinated
      activity of both glycosylphosphatidyl inositol-anchored MT4-MMP and the
      proteoglycan form of syndecan-1 on the cell surface.

PMID- 14701865
TI  - Inhibition of ligand-independent ERK1/2 activity in kidney proximal tubular cells
      deprived of soluble survival factors up-regulates Akt and prevents apoptosis.
AB  - Mouse kidney proximal tubular epithelial (MK-PT) cells die by apoptosis over 7-10
      days when deprived of all survival factors. We show here that withdrawal of all
      survival factors from MK-PT cells is associated with a progressive increase in
      the activity of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and a
      progressive decrease in phosphorylated Akt, a kinase critical to cell survival.
      Pharmacological inhibition of MEK1/2, the immediate upstream kinase for ERK1/2,
      not only prevented the decrease in phosphorylated Akt, but also prolonged MK-PT
      cell survival. Inhibition of ERK1/2, by itself, in the absence of any other known
      survival factors, was as potent as epidermal growth factor in maintaining MK-PT
      cell viability. ERK1/2 co-immunoprecipitated with Akt in a multimolecular
      assembly of signaling molecules, containing at a minimum ERK1/2, Akt, Rsk, and 3
      phosphoinositide dependent kinase 1 (PDK1). We hypothesize that the kinase Rsk,
      whose activation requires phosphorylation by both ERK1/2 and PDK1, acts as a
      bridge bringing ERK1/2 into proximity with PDK1-associated Akt. Although a number
      of interactions between the Raf-MEK-ERK and PI3K-Akt signaling pathways have been
      described, our results are the first to show modulation of Akt activity by
      signaling events originating with ERK1/2. Spontaneous activation of ERK1/2 occurs
      via MEK1/2 and appears to depend on oxidant stress, accompanying induction of the
      default pathway of apoptosis. Together, these data suggest that the spontaneous
      activation of ERK1/2, in the absence of known extracellular stimuli, represents a
      previously unrecognized major regulatory pathway determining the fate of cells
      destined to die by the default pathway of apoptosis.

PMID- 14701866
TI  - Calcium-sensing receptor-mediated ERK1/2 activation requires Galphai2 coupling
      and dynamin-independent receptor internalization.
AB  - The calcium-sensing receptor (CaR) recently has been shown to activate MAP kinase
      (ERK1/2) in various cell types as well as in heterologous expression systems. In
      this study we show that the CaR agonist NPS R-467 (1 microm), which does not
      activate the CaR by itself, robustly activates ERK1/2 in the presence of a low
      concentration of Ca(2+) (0.5 mm CaCl(2)) in human embryonic kidney (HEK) cells
      permanently expressing the human CaR (HEK-hCaR). Ca(2+) (4 mm) also activates
      ERK1/2 but with differing kinetics. CaR-dependent ERK1/2 activation begins to
      desensitize to 4 mm Ca(2+) after 10 min, whereas there is no desensitization to
      NPS R-467/CaCl(2) as late as 4 h. Moreover, recovery from desensitization occurs
      as rapidly as 30 min with 4 mm CaCl(2). Pretreatment of HEK-hCaR cells with
      concanavalin A (250 microg/ml) to block CaR internalization completely eliminated
      the NPS R-467/CaCl(2)-mediated ERK1/2 activation but did not block the 2-min time
      point of 4 mm Ca(2+)-mediated ERK1/2 activation. Neither dominant-negative
      dynamin (K44A) nor dominant-negative beta-arrestin inhibited ERK1/2 activation by
      either CaR agonist treatment, suggesting that CaR-elicited ERK1/2 signaling
      occurs via a dynamin-independent pathway. Pertussis toxin pretreatment partially
      attenuated the 4 mm Ca(2+)-ERK1/2 activation; this attenuated activity was
      completely restored by co-expression of the Galpha(i2) (C351I) but not Galpha(i1)
      (C351I) or Galpha(i3) (C351I) G proteins, PTX-insensitive G protein mutants.
      Taken together, these data suggest that both 4 mm Ca(2+) and NPS R-467/CaCl(2)
      activate ERK1/2 via distinguishable pathways in HEK-hCaR cells and may represent
      a nexus to differentially regulate differentiation versus proliferation via CaR
      activation.

PMID- 14701867
TI  - Physiological characterization of Haemophilus influenzae Rd deficient in its
      glutathione-dependent peroxidase PGdx.
AB  - The chimeric peroxidase PGdx of Haemophilus influenzae Rd belongs to a recently
      identified family of thiol peroxidases capable of reducing hydrogen peroxide as
      well as alkylhydroperoxides by means of glutathione redox cycling. In the present
      study, we constructed a H. influenzae Rd strain, deficient in its PGdx encoding
      gene (open reading frame HI0572). The mutant was shown by disk inhibition and
      liquid culture growth assays to exhibit increased susceptibility to organic
      hydroperoxides. The hampered growth was restored by complementing the interrupted
      gene on the genome with a replicating plasmid bearing an intact copy of the gene,
      hereby rejecting the possible influences of polar effects. Elevated levels of
      hydrogen peroxide scavenging activity, due to the catalase HktE, were measured in
      the absence of a functional pgdx gene rendering the mutant more resilient against
      hydrogen peroxide. On the other hand, after initiation of the stationary phase,
      aerobic cultures of the pgdx mutant were practically devoid of living cells,
      whereas wild-type counterparts retained viability. This observed feature was
      alleviated by complementation with the functional gene or with the addition of
      catalase.

PMID- 14701868
TI  - Identification of physiologically relevant substrates for cloned Gal: 3-O
      sulfotransferases (Gal3STs): distinct high affinity of Gal3ST-2 and LS180
      sulfotransferase for the globo H backbone, Gal3ST-3 for N-glycan multiterminal
      Galbeta1, 4GlcNAcbeta units and 6-sulfoGalbeta1, 4GlcNAcbeta, and Gal3ST-4 for
      the mucin core-2 trisaccharide.
AB  - Sulfated glycoconjugates regulate biological processes such as cell adhesion and
      cancer metastasis. We examined the acceptor specificities and kinetic properties
      of three cloned Gal:3-O-sulfotransferases (Gal3STs) ST-2, ST-3, and ST-4 along
      with a purified Gal3ST from colon carcinoma LS180 cells. Gal3ST-2 was the
      dominant Gal3ST in LS180. While the mucin core-2 structure
      Galbeta1,4GlcNAcbeta1,6(3-O-MeGalbeta1,3)GalNAcalpha-O-Bn (where Bn is benzyl)
      and the disaccharide Galbeta1,4GlcNAc served as high affinity acceptors for
      Gal3ST-2 and Gal3ST-3, 3-O-MeGalbeta1,4GlcNAcbeta1,-6(Galbeta1,3)GalNAcalpha-O-Bn
      and Galbeta1,3GalNAcalpha-O-Al (where Al is allyl) were efficient acceptors for
      Gal3ST-4. The activities of Gal3ST-2 and Gal3ST-3 could be distinguished with the
      Globo H precursor (Galbeta1,3GalNAcbeta1,3Galalpha-O-Me) and fetuin triantennary
      asialoglycopeptide. Gal3ST-2 acted efficiently on the former, while Gal3ST-3
      showed preference for the latter. Gal3ST-4 also acted on the Globo H precursor
      but not the glycopeptide. In support of the specificity, Gal3ST-2 activity toward
      the Galbeta1,4GlcNAcbeta unit on mucin core-2 as well as the Globo H precursor
      could be inhibited competitively by Galbeta1,4GlcNAcbeta1,6(3-O
      sulfoGalbeta1,3)GalNAcalpha-O-Bn but not 3-O-sulfoGalbeta1,
      4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-Bn. Remarkably these sulfotransferases
      were uniquely specific for sulfated substrates: Gal3ST-3 utilized Galbeta1,4(6-O
      sulfo)-GlcNAcbeta-O-Al as acceptor, Gal3ST-2 acted efficiently on Galbeta1,3(6-O
      sulfo)GlcNAcbeta-O-Al, and Gal3ST-4 acted efficiently on Galbeta1,3(6-O
      sulfo)GalNAcalpha-O-Al. Mg(2+), Mn(2+), and Ca(2+) stimulated the activities of
      Gal3ST-2, whereas only Mg(2+) augmented Gal3ST-3 activity. Divalent cations did
      not stimulate Gal3ST-4, although inhibition was noted at high Mn(2+)
      concentrations. The fine substrate specificities of Gal3STs indicate a distinct
      physiological role for each enzyme.

PMID- 14701869
TI  - The X-ray structure of trans-3-chloroacrylic acid dehalogenase reveals a novel
      hydration mechanism in the tautomerase superfamily.
AB  - Isomer-specific 3-chloroacrylic acid dehalogenases function in the bacterial
      degradation of 1,3-dichloropropene, a compound used in agriculture to kill plant
      parasitic nematodes. The crystal structure of the heterohexameric trans-3
      chloroacrylic acid dehalogenase (CaaD) from Pseudomonas pavonaceae 170
      inactivated by 3-bromopropiolate shows that Glu-52 in the alpha-subunit is
      positioned to function as the water-activating base for the addition of a
      hydroxyl group to C-3 of 3-chloroacrylate and 3-bromopropiolate, whereas the
      nearby Pro-1 in the beta-subunit is positioned to provide a proton to C-2. Two
      arginine residues, alphaArg-8 and alphaArg-11, interact with the C-1 carboxylate
      groups, thereby polarizing the alpha,beta-unsaturated acids. The reaction with 3
      chloroacrylate results in the production of an unstable halohydrin, 3-chloro-3
      hydroxypropanoate, which decomposes into the products malonate semialdehyde and
      HCl. In the inactivation mechanism, however, malonyl bromide is produced, which
      irreversibly alkylates the betaPro-1. CaaD is related to 4-oxalocrotonate
      tautomerase, with which it shares an N-terminal proline. However, in 4
      oxalocrotonate tautomerase, Pro-1 functions as a base participating in proton
      transfer within a hydrophobic active site, whereas in CaaD, the acidic proline is
      stabilized in a hydrophilic active site. The altered active site environment of
      CaaD thus facilitates a previously unknown reaction in the tautomerase
      superfamily, the hydration of the alpha,beta-unsaturated bonds of trans-3
      chloroacrylate and 3-bromopropiolate. The mechanism for these hydration reactions
      represents a novel catalytic strategy that results in carbon-halogen bond
      cleavage.

PMID- 14701870
TI  - Integration of Smad and MAPK pathways: a link and a linker revisited.

PMID- 14701871
TI  - Opportunities and challenges in the development of kinase inhibitor therapy for
      cancer.

PMID- 14701872
TI  - Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural
      induction.
AB  - How do very diverse signaling pathways induce neural differentiation in Xenopus?
      Anti-BMP (Chordin), FGF8, and IGF2 signals are integrated in the embryo via the
      regulation of Smad1 phosphorylation. Neural induction results from the combined
      inhibition of BMP receptor serine/threonine kinases and activation of receptor
      tyrosine kinases that signal through MAPK and phosphorylate Smad1 in the linker
      region, further inhibiting Smad1 transcriptional activity. This hard-wired
      molecular mechanism at the level of the Smad1 transcription factor may help
      explain the opposing activities of IGF, FGF, and BMP signals not only in neural
      induction, but also in other aspects of vertebrate development.

PMID- 14701873
TI  - Similar MLL-associated leukemias arising from self-renewing stem cells and short
      lived myeloid progenitors.
AB  - We have used the hematopoietic system as a model to investigate whether acute
      myeloid leukemia arises exclusively from self-renewing stem cells or also from
      short-lived myeloid progenitors. When transduced with a leukemogenic MLL fusion
      gene, prospectively isolated stem cells and myeloid progenitor populations with
      granulocyte/macrophage differentiation potential are efficiently immortalized in
      vitro and result in the rapid onset of acute myeloid leukemia with similar
      latencies following transplantation in vivo. Regardless of initiating cell,
      leukemias displayed immunophenotypes and gene expression profiles characteristic
      of maturation arrest at an identical late stage of myelomonocytic
      differentiation, putatively a monopotent monocytic progenitor stage. Our findings
      unequivocally establish the ability of transient repopulating progenitors to
      initiate myeloid leukemias in response to an MLL oncogene, and support the
      existence of cancer stem cells that do not necessarily overlap with multipotent
      stem cells of the tissue of origin.

PMID- 14701874
TI  - SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin
      mu gene expression.
AB  - Nuclear matrix attachment regions (MARs) are regulatory DNA sequences that are
      important for higher-order chromatin organization, long-range enhancer function,
      and extension of chromatin modifications. Here we characterize a novel cell type
      specific MAR-binding protein, SATB2, which binds to the MARs of the endogenous
      immunoglobulin micro locus in pre-B cells and enhances gene expression. We found
      that SATB2 differs from the closely related thymocyte-specific protein SATB1 by
      modifications of two lysines with the small ubiquitive related modifier (SUMO),
      which are augmented specifically by the SUMO E3 ligase PIAS1. Mutations of the
      SUMO conjugation sites of SATB2 enhance its activation potential and association
      with endogenous MARs in vivo, whereas N-terminal fusions with SUMO1 or SUMO3
      decrease SATB2-mediated gene activation. Sumoylation is also involved in
      targeting SATB2 to the nuclear periphery, raising the possibility that this
      reversible modification of a MAR-binding protein may contribute to the modulation
      of subnuclear DNA localization.

PMID- 14701875
TI  - Tap and NXT promote translation of unspliced mRNA.
AB  - Tap has been proposed to play a role in general mRNA export and also functions in
      expression of RNA with retained introns that contain the MPMV CTE (constitutive
      transport element). Tap forms a functional heterodimer with NXT/p15. We have
      previously demonstrated that unspliced intron-containing CTE RNA is efficiently
      exported to the cytoplasm in mammalian cells. Here we show that Tap and NXT
      proteins function together to enhance translation of proteins from the exported
      CTE RNA. Pulse chase experiments show that Tap/NXT significantly increases the
      rate of protein synthesis. Sucrose gradient analysis demonstrates that Tap and
      NXT efficiently shift the unspliced RNA into polyribosomal fractions.
      Furthermore, Tap, but not NXT is detected in polyribosomes. Taken together, our
      results indicate that Tap and NXT serve a role in translational regulation of RNA
      after export to the cytoplasm. They further suggest that Tap/NXT may play a role
      in remodeling of cytoplasmic RNP complexes, providing a link between export
      pathways and cytoplasmic fate.

PMID- 14701876
TI  - Antagonists of Wnt and BMP signaling promote the formation of vertebrate head
      muscle.
AB  - Recent studies have postulated that distinct regulatory cascades control myogenic
      differentiation in the head and the trunk. However, although the tissues and
      signaling molecules that induce skeletal myogenesis in the trunk have been
      identified, the source of the signals that trigger skeletal muscle formation in
      the head remain obscure. Here we show that although myogenesis in the trunk
      paraxial mesoderm is induced by Wnt signals from the dorsal neural tube,
      myogenesis in the cranial paraxial mesoderm is blocked by these same signals. In
      addition, BMP family members that are expressed in both the dorsal neural tube
      and surface ectoderm are also potent inhibitors of myogenesis in the cranial
      paraxial mesoderm. We provide evidence suggesting that skeletal myogenesis in the
      head is induced by the BMP inhibitors, Noggin and Gremlin, and the Wnt inhibitor,
      Frzb. These molecules are secreted by both cranial neural crest cells and by
      other tissues surrounding the cranial muscle anlagen. Our findings demonstrate
      that head muscle formation is locally repressed by Wnt and BMP signals and
      induced by antagonists of these signaling pathways secreted by adjacent tissues.

PMID- 14701877
TI  - Post-transcriptional regulation of the E/Daughterless ortholog HLH-2, negative
      feedback, and birth order bias during the AC/VU decision in C. elegans.
AB  - The anchor cell/ventral uterine precursor cell (AC/VU) decision in Caenorhabditis
      elegans is a canonical example of lin-12/Notch-mediated lateral specification.
      Two initially equivalent cells interact via the receptor LIN-12 and its ligand
      LAG-2, so that one becomes the AC and the other a VU. During this interaction,
      feedback loops amplify a small difference in lin-12 activity, limiting lin-12
      transcription to the presumptive VU and lag-2 transcription to the presumptive
      AC. Here, we find that hlh-2 appears to be required for the VU fate and directly
      activates lag-2 transcription in the presumptive AC. HLH-2 appears to accumulate
      selectively in the presumptive AC prior to differential transcription of lin-12
      or lag-2, and is therefore the earliest detectable difference between the two
      cells undergoing the AC/VU decision. The restricted accumulation of HLH-2 to the
      presumptive AC reflects post-transcriptional down-regulation of HLH-2 in the
      presumptive VU. Our observations suggest that hlh-2 is regulated as part of the
      negative feedback that down-regulates lag-2 transcription in the presumptive VU.
      Finally, we show that the AC/VU decision in an individual hermaphrodite is biased
      by the relative birth order of the two cells, so that the first-born cell is more
      likely to become the VU. We propose models to suggest how birth order, HLH-2
      accumulation, and transcription of lag-2 may be linked during the AC/VU decision.

PMID- 14701878
TI  - hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the
      perinuclear region.
AB  - Human immunodeficiency virus Rev facilitates the cytoplasmic accumulation of
      viral RNAs that contain a Rev binding site. A human Rev-interacting protein
      (hRIP) was originally identified based on its ability to interact with the Rev
      nuclear export signal (NES) in yeast two-hybrid assays. To date, however, the
      function of hRIP and a role for hRIP in Rev-directed RNA export have remained
      elusive. Here we ablate hRIP activity with a dominant-negative mutant or RNA
      interference and analyze Rev function by RNA in situ hybridization. We find,
      unexpectedly, that in the absence of functional hRIP, Rev-directed RNAs
      mislocalize and aberrantly accumulate at the nuclear periphery, where hRIP is
      localized. In contrast, in the absence of Rev or the Rev cofactor CRM1, Rev
      directed RNAs remain nuclear. We further show that the RNA mislocalization
      pattern resulting from loss of hRIP activity is highly specific to Rev function:
      the intracellular distribution of cellular poly(A)(+) mRNA, nuclear proteins,
      and, most important, NES-containing proteins, are unaffected. Thus, hRIP is an
      essential cellular Rev cofactor, which acts at a previously unanticipated step in
      HIV-1 RNA export: movement of RNAs from the nuclear periphery to the cytoplasm.

PMID- 14701879
TI  - In vivo requirements for rDNA chromosome condensation reveal two cell-cycle
      regulated pathways for mitotic chromosome folding.
AB  - Chromosome condensation plays an essential role in the maintenance of genetic
      integrity. Using genetic, cell biological, and biochemical approaches, we
      distinguish two cell-cycle-regulated pathways for chromosome condensation in
      budding yeast. From G(2) to metaphase, we show that the condensation of the
      approximately 1-Mb rDNA array is a multistep process, and describe condensin
      dependent clustering, alignment, and resolution steps in chromosome folding. We
      functionally define a further postmetaphase chromosome assembly maturation step
      that is required for the maintenance of chromosome structural integrity during
      segregation. This late step in condensation requires the conserved mitotic kinase
      Ipl1/aurora in addition to condensin, but is independent of cohesin. Consistent
      with this, the late condensation pathway is initiated during the metaphase-to
      anaphase transition, supports de novo condensation in cohesin mutants, and
      correlates with the Ipl1/aurora-dependent phosphorylation of condensin. These
      data provide insight into the molecular mechanisms of higher-order chromosome
      folding and suggest that two distinct condensation pathways, one involving
      cohesins and the other Ipl1/aurora, are required to modulate chromosome structure
      during mitosis.

PMID- 14701880
TI  - GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs.
AB  - The conserved RCN family of proteins can bind and directly regulate calcineurin,
      a Ca(2+)-activated protein phosphatase involved in immunity, heart growth, muscle
      development, learning, and other processes. Whereas high levels of RCNs can
      inhibit calcineurin signaling in fungal and animal cells, RCNs can also stimulate
      calcineurin signaling when expressed at endogenous levels. Here we show that the
      stimulatory effect of yeast Rcn1 involves phosphorylation of a conserved serine
      residue by Mck1, a member of the GSK-3 family of protein kinases. Mutations at
      the GSK-3 consensus site of Rcn1 and human DSCR1/MCIP1 abolish the stimulatory
      effects on calcineurin signaling. RCNs may therefore oscillate between
      stimulatory and inhibitory forms in vivo in a manner similar to the Inhibitor-2
      regulators of type 1 protein phosphatase. Computational modeling indicates a
      biphasic response of calcineurin to increasing RCN concentration such that
      protein phosphatase activity is stimulated by low concentrations of phospho-RCN
      and inhibited by high concentrations of phospho- or dephospho-RCN. This
      prediction was verified experimentally in yeast cells expressing Rcn1 or
      DSCR1/MCIP1 at different concentrations. Through the phosphorylation of RCNs, GSK
      3 kinases can potentially contribute to a positive feedback loop involving
      calcineurin-dependent up-regulation of RCN expression. Such feedback may help
      explain the large induction of DSCR1/MCIP1 observed in brain of Down syndrome
      individuals.

PMID- 14701881
TI  - Notch promotes epithelial-mesenchymal transition during cardiac development and
      oncogenic transformation.
AB  - Epithelial-to-mesenchymal transition (EMT) is fundamental to both embryogenesis
      and tumor metastasis. The Notch intercellular signaling pathway regulates cell
      fate determination throughout metazoan evolution, and overexpression of
      activating alleles is oncogenic in mammals. Here we demonstrate that Notch
      activity promotes EMT during both cardiac development and oncogenic
      transformation via transcriptional induction of the Snail repressor, a potent and
      evolutionarily conserved mediator of EMT in many tissues and tumor types. In the
      embryonic heart, Notch functions via lateral induction to promote a selective
      transforming growth factor-beta (TGFbeta)-mediated EMT that leads to
      cellularization of developing cardiac valvular primordia. Embryos that lack Notch
      signaling elements exhibit severely attenuated cardiac snail expression, abnormal
      maintenance of intercellular endocardial adhesion complexes, and abortive
      endocardial EMT in vivo and in vitro. Accordingly, transient ectopic expression
      of activated Notch1 (N1IC) in zebrafish embryos leads to hypercellular cardiac
      valves, whereas Notch inhibition prevents valve development. Overexpression of
      N1IC in immortalized endothelial cells in vitro induces EMT accompanied by
      oncogenic transformation, with corresponding induction of snail and repression of
      VE-cadherin expression. Notch is expressed in embryonic regions where EMT occurs,
      suggesting an intimate and fundamental role for Notch, which may be reactivated
      during tumor metastasis.

PMID- 14701883
TI  - Continuity of care: an essential element of modern general practice?
AB  - For a variety of reasons, GPs are working more and more with unfamiliar patients.
      The proposed new British GP contract stipulates that in future patients will
      register with a practice, rather than with a named GP and a recent new definition
      of general practice did not mention continuing care. There has been persistent
      confusion about the definition of continuity of care. Evidence for the benefit of
      patients usually seeing the same doctor is still limited. In this paper we
      describe some discrete elements of continuity, emphasize the importance of
      interpersonal continuity and suggest how this may work. The contributions of
      informational continuity (especially good records) and of excellent consulting
      skills are put in context. We conclude that further evidence is needed to
      demonstrate the added value of interpersonal continuity in general practice and
      that this needs a clear theoretical basis. We propose that such a theory will
      define the concept of multi-dimensional diagnosis as the key strength of our
      discipline and that continuity, especially interpersonal continuity, is an
      important factor in achieving this economically and in a way which satisfies both
      patients and professionals.

PMID- 14701882
TI  - What determines whether mammalian ribosomes resume scanning after translation of
      a short upstream open reading frame?
AB  - If the 5'-proximal AUG triplet in a mammalian mRNA is followed by a short open
      reading frame (sORF), a significant fraction of ribosomes resume scanning after
      termination of sORF translation, and reinitiate at a downstream AUG. To examine
      the underlying mechanism, we examined reinitiation in vitro using a series of
      mRNAs that differed only in the 5'-untranslated region (UTR). Efficient
      reinitiation was found to occur only if the eIF4F complex, or at a minimum the
      central one-third fragment of eIF4G, participated in the primary initiation event
      at the sORF initiation codon. It did not occur, however, when sORF translation
      was driven by the classical swine fever virus or cricket paralysis virus internal
      ribosome entry sites (IRESs), which do not use eIF4A, 4B, 4E, or 4G. A critical
      test was provided by an mRNA with an unstructured 5'-UTR, which is translated by
      scanning but does not absolutely need eIF4G and eIF4A: There was efficient
      reinitiation in a standard reticulocyte lysate, when initiation would be largely
      driven by eIF4F, but no reinitiation in an eIF4G-depleted lysate. These results
      suggest that resumption of scanning may depend on the interaction between eIF4F
      (or the eIF4G central domain) and the ribosome being maintained while the
      ribosome translates the sORF.

PMID- 14701884
TI  - Breaking up is never easy: GPs' accounts of removing patients from their lists.
AB  - OBJECTIVE: The aim of this study was to understand why GPs choose to end their
      relationship with patients by removing them from their lists. METHODS: Semi
      structured interviews were carried out with 25 GPs from 22 general practices in
      Leicestershire. Qualitative analysis was performed using the constant comparative
      method. The main outcome measures were participants' accounts of removing
      patients from their lists. RESULTS: GPs use removal as a means of ending their
      professional relationships with problematic patients. All of the doctors
      indicated that they wished to retain the right to remove patients and stressed
      that removal is a rare event which they only use as a "last resort". There are
      two distinct but overlapping types of patients who are most likely to become
      eligible for removal: "bad" patients, who break the rules of the doctor-patient
      or practice-patient relationship, and "difficult" patients, with whom the doctor
      patient relationship is so strained that doctors feel they can no longer care for
      them. The doctors may choose to remove a patient without warning or else to write
      a short letter giving "relationship breakdown" as the reason. They find it hard
      to confront the patient openly about the difficulties in the relationship.
      CONCLUSIONS: The ability to remove patients is a right that GPs value. They
      report that it is rare for them to seek to end their relationships with patients
      and, when they do, it is for reasons that are important in the maintenance of
      professional boundaries or fulfilling professional responsibilities.

PMID- 14701885
TI  - A caring partnership: expectations of ageing persons with disabilities for their
      primary care doctors.
AB  - BACKGROUND: The population of individuals who are ageing with a disability is
      growing rapidly, yet we know little about their views of their primary care and
      family physicians. METHOD: In this qualitative study using a modified form of
      life history interviewing, 30 older respondents with a variety of disabilities
      discussed their past and current relationships with physicians. RESULTS: Data
      analysis identified as the primary theme of these interviews the importance of
      establishing a caring partnership between patient and physician. Important
      subthemes included physician avoidance of assumptions and stereotypes about
      persons with disabilities, physician commitment to patient well-being balanced by
      a capacity for keeping the disability in perspective, and the relationship
      between the need for physician specialized knowledge and the necessity of
      acknowledging patient expertise. Certain patient characteristics such as self
      reliance and assertiveness also emerged as significant influences. CONCLUSION: A
      partnership with primary care/family physicians that communicates concern while
      avoiding stereotyping and recognizing patient expertise is important for many
      patients ageing with a disability.

PMID- 14701886
TI  - The effect of an integrated care approach for heart failure on general practice.
AB  - BACKGROUND: Recent studies have investigated specific strategies for heart
      failure management. None has involved collaboration between primary and secondary
      care. Potential gains for patients may result from collaborative strategies.
      OBJECTIVE: To assess the effect of an integrated management approach for patients
      with heart failure on general practice. METHODS: The study design was a cluster
      randomized controlled trial of integrated primary/ secondary care compared with
      usual care for heart failure patients. The study took place at Auckland Hospital,
      New Zealand and involved 197 patients admitted with an episode of heart failure.
      Patients were randomized to management group or control group (who received
      "usual" care). Management group patients received early clinical review,
      education sessions, a personal diary for medications and weight, and regular
      clinical follow-up alternating between GP and hospital clinic. Follow-up was for
      12 months. RESULTS: Patients visited GPs frequently (median 14 visits, range 0
      40), with no statistical difference between the two groups. Heart failure was the
      most common reason for consulting the GP. There was no relationship between GP
      consultations and patients' attendance at the study clinic, or hospital
      admissions. Management group GPs and patients expressed a high level of
      satisfaction. CONCLUSION: GP consultation rates were not affected by the
      programme. Further research will determine if general practice based programmes
      result in further gains.

PMID- 14701887
TI  - Cluster randomized trial of a guideline-based open access urological
      investigation service.
AB  - BACKGROUND: Out-patient services are trying to achieve effective and efficient
      health care in overcrowded, busy clinic settings. "One stop" and "open access"
      clinics have been advocated as a way of improving out-patient services.
      OBJECTIVES: Our aim was to evaluate the effectiveness and efficiency of a
      guideline-based open access urological investigation service. METHODS: General
      practices were randomized to receive either referral guidelines and access to the
      investigation service for lower urinary tract symptoms (LUTS) or referral
      guidelines and access to the investigation service for microscopic haematuria
      (MH). The study population comprised 66 general practices in the Grampian region
      of Scotland referring 959 patients. The outcome measures were compliance with
      guidelines (number of recommended investigations completed), number of general
      practice consultations, the number and case mix of referrals, waiting time to
      initial hospital appointment, and the number of patients with a management
      decision reached at initial appointment and discharged by 12 months after
      referral. RESULTS: GPs' compliance with referral guidelines increased (difference
      in means 0.5; 95% confidence interval 0.2-0.8, P < 0.001). Approximately 50% of
      eligible patients were referred through the new system. The number and case mix
      of referrals were similar. The intervention reduced the waiting time from
      referral to initial out-patient appointment (ratio of means 0.7; 0.5-0.9,
      patients with LUTS only) and increased the number of patients who had a
      management decision reached at initial appointment (odds ratio 5.8; 2.9-11.5, P <
      0.00001, both conditions). Patients were more likely to be discharged within 12
      months (odds ratio 1.7; 0.9-3.3, P = 0.11). There were no significant changes
      detected in patient outcomes. Overall the new service was probably cost saving to
      the NHS. CONCLUSIONS: The guideline-based open access investigation service
      streamlined the process of out-patient referral, resulting in a more efficient
      service with reduced out-patient waiting times, fewer out-patient and
      investigation appointments and release of specialist and clinic time.

PMID- 14701888
TI  - Promoting better use of the PSA test in general practice: randomized controlled
      trial of educational strategies based on outreach visits and mailout.
AB  - BACKGROUND: Prostate-specific antigen (PSA) testing for prostate cancer is
      controversial. Demand for PSA testing is likely to rise in the UK, Australia and
      other western countries. Primary care needs to develop appropriate strategies to
      respond to this demand. OBJECTIVES: Our aim was to compare the effectiveness of
      educational outreach visits (EOVs) and mailout strategies targeting PSA testing
      in Australian primary care. METHODS: A randomized controlled trial was conducted
      in general practices in southern Adelaide. The main outcome measures at baseline,
      6 months and 12 months post-intervention were PSA testing rates and GP knowledge
      in key areas relating to prostate cancer and PSA testing. RESULTS: The
      interventions were able to demonstrate a change in clinical practice. In the 6
      months post-intervention, median PSA testing rate in the EOV group was
      significantly lower than in the postal group, which in turn was significantly
      lower than the control group (P < 0.001). Statistically significant differences
      were not, however, maintained in the 6-12 month post-intervention period. The EOV
      group, at 6 months follow-up, had a significantly greater proportion of "correct"
      responses than the control group to questions about prostate cancer treatment
      effectiveness (P = 0.004) and endorsement of PSA screening by professional bodies
      (P = 0.041). CONCLUSIONS: Primary care has a central role in PSA testing for
      prostate cancer. Clinical practice in this area is receptive to evidence-based
      interventions.

PMID- 14701889
TI  - Randomized osteopathic manipulation study (ROMANS): pragmatic trial for spinal
      pain in primary care.
AB  - BACKGROUND: Spinal pain is common and frequently disabling. Management guidelines
      have encouraged referral from primary care for spinal manipulation. However, the
      evidence base for these recommendations is weak. More pragmatic trials and
      economic evaluations have been recommended. OBJECTIVES: Our aim was to assess the
      effectiveness and health care costs of a practice-based osteopathy clinic for
      subacute spinal pain. METHODS: A pragmatic randomized controlled trial was
      carried out in a primary care osteopathy clinic accepting referrals from 14
      neighbouring practices in North West Wales. A total of 201 patients with neck or
      back pain of 2-12 weeks duration were allocated at random between usual GP care
      and an additional three sessions of osteopathic spinal manipulation. The primary
      outcome measure was the Extended Aberdeen Spine Pain Scale (EASPS). Secondary
      measures included SF-12, EuroQol and Short-form McGill Pain Questionnaire. Health
      care costs were estimated from the records of referring GPs. RESULTS: Outcomes
      improved more in the osteopathy group than the usual care group. At 2 months,
      this improvement was significantly greater in EASPS [95% confidence interval (CI)
      0.7-9.8] and SF-12 mental score (95% CI 2.7-10.7). At 6 months, this difference
      was no longer significant for EASPS (95% CI -1.5 to 10.4), but remained
      significant for SF-12 mental score (95% CI 1.0-9.9). Mean health care costs
      attributed to spinal pain were significantly greater by 65 UK pounds in the
      osteopathy group (95% CI 32-155 UK pounds). Though osteopathy also cost 22 UK
      pounds more in mean total health care cost, this was not significant (95% CI -
      159 to 142 UK pounds). CONCLUSION: A primary care osteopathy clinic improved
      short-term physical and longer term psychological outcomes, at little extra cost.
      Rigorous multicentre studies are now needed to assess the generalizability of
      this approach.

PMID- 14701890
TI  - Family practitioners' attitudes and knowledge about irritable bowel syndrome:
      effect of a trial of physician education.
AB  - BACKGROUND: Primary physicians care for most patients with irritable bowel
      syndrome (IBS), but data on their attitudes and knowledge about the disorder are
      limited to research in the UK. OBJECTIVE: The purpose of the present study was to
      assess US family practitioners' attitudes and knowledge about IBS and determine
      the effect of a single education class on these measures. METHODS: In a large
      health maintenance organization (HMO), a baseline group of family practitioners
      twice completed a questionnaire on attitudes and knowledge about IBS, 3 months
      apart. A class group completed it pre-class, immediately post-class and 3 months
      post-class. RESULT: Thirty-five physicians ranked IBS among five chronic, painful
      syndromes as highest in difficulty satisfying patients, tied with headache for
      highest in difficulty in practice strategy decision, second in time required, and
      fourth in diagnostic confidence and satisfaction in caring for patients. IBS and
      heartburn had widely separated rankings in all five attitudes. The correct answer
      rate on seven of 13 knowledge questions was <50%, and a majority did not identify
      the Rome II symptom criteria as typical and lacked other important knowledge. Of
      the 30 class physicians, the knowledge scores (mean +/- SD; maximum possible, 13)
      of 29 increased from 5.59 +/- 1.84 pre-class to 10.21 +/- 1.76 immediately post
      class (P < 0.0001); 3 months later, the scores were lower (8.93 +/- 0.36) than
      post-class (P < 0.0001), but still higher than pre-class (P < 0.0001). Their
      attitude rankings were nearly identical pre-class and 3 months later (P > 0.05).
      In the 19 baseline physicians, IBS attitude rankings and knowledge scores did not
      change significantly over 3 months (P > 0.05). CONCLUSION: These US family
      practitioners had attitudes about IBS patients and lacked knowledge that could
      interfere with patient care. A single class improved short-term knowledge but had
      little effect on attitudes about IBS.

PMID- 14701891
TI  - A qualitative evaluation of implementing a randomized controlled trial in general
      practice.
AB  - BACKGROUND: For findings of randomized controlled trials in primary care to be
      applicable, both the sample of clinicians implementing the trial and the
      recruited patients should be as representative as possible. The processes of
      conducting trials should be made "user-friendly" to clinician investigators in
      order to maximize their participation in research. Formal evaluations of trial
      implementation are unusual. This study reports clinicians' perspectives on acting
      as a clinician investigator in a randomized controlled trial (the SAVIT study) in
      general practice. OBJECTIVE: Our purpose was to explore clinicians' accounts of
      taking part in a randomized controlled trial in which subjects were recruited
      opportunistically during general practice consultations. METHOD: Individual semi
      structured interviews were conducted with nine GPs and one practice nurse
      practising in the Bro Taf area of South Wales who recruited children into the
      SAVIT study. A structured interview guide was used and data were analysed using
      the qualitative method of pattern coding. RESULTS: Major emerging themes included
      recruitment difficulties and concerns about the safety of the study medication.
      Participants also outlined positive aspects of the study (clarity and simplicity
      of the study, potential benefits to clinicians and patients and study team follow
      up of recruited patients). Recommendations for possible improvements in study
      implementation included the simplification and reduction of patient reading
      materials and improved presentation of study materials. CONCLUSIONS: Difficulty
      in recruiting patients was the most frequently mentioned problem by clinician
      investigators. Insufficient time in the consultation was perceived as the main
      barrier. Ingredients of successful trial implementation include good
      organization, simple documentation and study procedures, and the ability to allay
      concerns about patient safety. Findings from this evaluation may assist
      researchers in the design and implementation of future community-based randomized
      controlled trials.

PMID- 14701892
TI  - Performance of a single screening question for depression in a representative
      sample of 13 670 people aged 75 and over in the UK: results from the MRC trial of
      assessment and management of older people in the community.
AB  - BACKGROUND: A concise, accurate screening question for depression would be an
      important contribution to the Single Assessment Process for Older People.
      OBJECTIVE: To examine the performance of a previously validated screening
      question for depression, in a large community sample. METHODS: Both the single
      screening question, and the Geriatric Depression Scale (GDS-15) were completed by
      13 670 people aged 75 and over in the community. Responses to the question were
      compared with a "standard" of scoring above different thresholds on the Geriatric
      Depression Scale (GDS-15). RESULTS: For more severe GDS-15 depression, the best
      performance of the question was a sensitivity of only 52% and a specificity of
      93%. CONCLUSION: Even at its best, the question therefore misses almost half the
      cases. This highlights the problems of such simple approaches to routine
      screening.

PMID- 14701893
TI  - A 5-year follow-up of general practice patients experiencing depression.
AB  - BACKGROUND: Depression is a common disease in primary care and produces
      significant morbidity in the community. Little is known about the outcomes of
      depression in general practice. OBJECTIVES: This research set out to explore both
      the longitudinal management and outcomes of depression as seen in general
      practice. METHODS: The Medic-GP database is a collection of the medical records
      of >50 000 people seen in nine Australian general practices. It was used to
      follow the management of depressed patients over 4-5 years. Records from 1994
      1995 were searched for depression or similar words. Individual records of
      patients whose notes mentioned depression were randomly selected and examined to
      determine if they were diagnosed with depression. Records of patients who were
      diagnosed as suffering from depression were examined to determine progress over
      the ensuing 5 years. RESULTS: Six hundred of 5889 patients were examined in
      detail. A total of 382 patients (63.7%) were diagnosed with depression; 219 had
      been diagnosed during this time interval. The main findings were 64.7% of
      patients were female; 93.6% of patients received an antidepressant at some time
      during the study; 16% of patients were referred to a psychiatrist; 7.3% were
      hospitalized; 30% of patients who ceased antidepressants without a recurrence had
      courses of antidepressants of 3 months or less; and only 22.5% of patients had a
      single episode of depression. CONCLUSION: Unlike cross-sectional studies, this
      study has shown a high rate of prescription of antidepressants. GPs often
      prescribed short courses of antidepressants, and depression behaves as a chronic,
      recurrent disease.

PMID- 14701894
TI  - Barriers to seeking treatment for sexual problems in primary care: a qualitative
      study with older people.
AB  - BACKGROUND: Although it is known that only a small minority of people
      experiencing sexual problems seek treatment for these, barriers to treatment
      seeking remain relatively unexplored. This is particularly true for older people,
      whose perceived "asexuality" has led to them being excluded from sexual health
      research. OBJECTIVE: The aim of the present study was to identify barriers
      experienced by older people in seeking treatment for sexual problems. METHODS:
      Semi-structured interviews were conducted with 22 women and 23 men aged 50-92
      years recruited from the age/sex register of a Sheffield general practice. A
      central component of the interviews involved exploring participants' attitudes
      towards, and experiences of, seeking help for sexual problems. Interviews were
      analyzed using the "framework" approach. RESULTS: The GP was seen as the main
      source of professional help if sexual problems were experienced. However, several
      barriers were identified as inhibiting help being sought. These included the
      demographic characteristics of the GP, GP attitudes towards later life sexuality,
      the attribution of sexual problems to "normal ageing", shame/embarrassment and
      fear, perceiving sexual problems as "not serious" and lack of knowledge about
      appropriate services. Twenty-five participants had experienced recent sexual
      problems which informed their responses. CONCLUSION: These findings indicate that
      many older people have sexual problems that they would like to discuss with their
      GP, but they feel unable to do so. GPs may need to be more proactive in raising
      sexual health issues in consultations if these needs are to be met.

PMID- 14701895
TI  - The duration of acute cough in pre-school children presenting to primary care: a
      prospective cohort study.
AB  - BACKGROUND: Professional and parental uncertainty about the natural history of
      cough in pre-school children may in part be responsible for the high consultation
      and reconsultation rates and widespread antibiotic use in primary care. A recent
      systematic review of the natural history of cough included studies of
      unrepresentative, selected patients with heterogeneous measures and definitions
      of cough duration. OBJECTIVES: The aim of the present study was to describe the
      post-consultation duration of cough, compare this with clinician and parental
      prediction of cough duration, and to determine the clinical factors associated
      with prolonged cough. METHODS: A prospective cohort study of children aged 0-4
      years with cough < or =28 days without asthma presenting to eight general
      practices in Leicestershire, UK was carried out. Socio-demographic and clinical
      data were collected, and parents and clinicians were asked to predict the
      proportion recovering within 7, 14, 21 and 28 days. Parents used a symptom diary
      to record cough and five other symptoms. Survival analysis was used to describe
      cough duration, and multivariable Cox regression was used to identify the factors
      independently associated with prolonged cough. RESULTS: Fifty percent of the
      children had recovered at 10 days and 90% at 25 days. Cough was associated with
      fever, breathlessness, disrupted sleep and reduced activity in a high proportion
      of children. Longer post-consultation cough was associated with longer pre
      consultation cough and use of day care facilities. Clinicians overestimated how
      quickly children recovered from acute cough. Parents' predictions were accurate
      within 2 weeks, but they underestimated the proportion recovering in weeks 3 and
      4. CONCLUSIONS: Clinicians should be aware that from the parental perspective,
      acute cough is not a trivial illness and that some children remain unwell at 3-4
      weeks. For health professionals negotiating the use of antibiotics, this
      information may enable parental self-care, reduce medicalization and displace the
      need to prescribe.

PMID- 14701896
TI  - Optimal strategies for identifying patients with myocardial infarction in general
      practice.
AB  - BACKGROUND: In order to provide evidence-based secondary prevention of coronary
      heart disease (CHD) in general practice, eligible patients need to be identified.
      The optimal strategy is one in which all appropriate patients are identified with
      the least effort. OBJECTIVE: The purpose of the study was to determine the
      optimal strategy to identify subjects with a myocardial infarction (MI) from
      general practice records using different search criteria. METHODS: The study was
      a cross-sectional survey of 10 general practices in Tayside, Scotland. A random
      sample of all subjects aged over 35 (n = 5061) and registered with the general
      practices was obtained. The main outcome measures were sensitivity, specificity,
      positive predictive value (PPV) and yield (the number of records that need to be
      examined to detect a "true case"). RESULTS: Of the sample of 5061, 207 (4.1%)
      were defined to have had a "gold standard" MI. A Read code for ischaemic heart
      disease (IHD) had the highest sensitivity (95%) but with a poor PPV (52%). All
      searches had high specificities. The addition of a record of hospitalization for
      MI to the Read code for MI gave 100% sensitivity and high yield (1 in 1.11). In
      situations where the Read coding is of poor quality, the alternative search
      strategy of a hospital record of MI or receiving aspirin or nitrates was optimum.
      CONCLUSIONS: Patients who had experienced an MI can be easily identified from a
      combination of a Read code for MI and a record of hospitalization for an MI
      giving 100% sensitivity and specificity with a yield of 1 in 1.11.

PMID- 14701897
TI  - Victim-blaming revisited: a qualitative study of beliefs about illness causation,
      and responses to chest pain.
AB  - BACKGROUND: Health promotion is an established part of the general practice
      consultation. It is widely acknowledged that risk-behaviours are strongly
      affected by socio-economic status and the structural constraints of the
      individual, but little is known about the possible negative effects of lifestyle
      advice. OBJECTIVES: To examine the extent to which self-responsibility, blame for
      ill health and risk behaviours feature in accounts of respondents with chest
      pain, and to ascertain whether perceived victim-blaming influences lay
      interpretations and responses to chest pain, and to ill health in general.
      METHODS: Qualitative interviews were carried out in two socio-economically
      contrasting areas of Glasgow, with 30 respondents (15 men and 15 women) from a
      socio-economically deprived area, and 30 respondents (15 men and 15 women) from
      an affluent area. RESULTS: Respondents recognized the causative links between
      well-established cardiac risk factors and heart disease. Individuals blamed
      themselves for their heart disease and general ill health and many also believed
      that they would be blamed for their behaviour and health problems by doctors. For
      some respondents, self-blame and fear of blame appeared to contribute to a
      reluctance to seek care. Self-blame, experience of blame and fear of blame were
      more common in respondents from the deprived area. CONCLUSION: Emphasis by
      doctors on "unhealthy" behaviours may deter patients from seeking medical care.
      Lifestyle advice should be given taking into account the health beliefs and the
      socio-economic context of individuals. Future studies should focus on the theme
      of blame in order to explore further the possible negative effects of lifestyle
      advice given by health professionals.

PMID- 14701898
TI  - Childhood illnesses and the use of paracetamol (acetaminophen): a qualitative
      study of parents' management of common childhood illnesses.
AB  - OBJECTIVES: Parents frequently give over-the-counter paracetamol (acetaminophen)
      during childhood illness. This study aims at exploring parents' use of this
      medicine in relation to their management of common childhood illnesses and the
      impact on the family. METHODS: Parents of pre-school aged children were asked
      open-ended questions about their perceptions of illness, its impact on the
      family, the use of paracetamol and sources of medical information. The interviews
      were audiotaped. The transcribed text was condensed and different views and
      opinions were identified for each question. The parents were recruited from six
      Norwegian public health centres during a questionnaire study on the use of
      paracetamol among their children. Volunteering parents supplied their name and
      telephone number for further contact. A strategic sample of 24 parents was
      selected for interviews according to their responses to the questionnaire and
      family characteristics. RESULTS: Parents recognized illness among their children
      either intuitively or by taking notice of specific signs or symptoms. Fever was
      considered a definite sign of illness, almost congruent with the disease itself.
      Some parents acknowledged that low or moderate fever reflected a battle between
      the body and the disease-causing organism. High or rapidly increasing fever,
      however, was frequently looked upon as dangerous. Mothers preferred to stay close
      to their child during illness and postponed other duties. Inexperienced parents
      felt particularly anxious and helpless since they often found the severity of the
      illness difficult to judge. Administration of paracetamol gave parents the
      feeling of mastery. The medicine was also used to calm down the child enabling
      sleep and rest for the whole family. Some parents were generally interested in
      information about child diseases, others were only eager to know more about it
      during periods of illness, and some parents were not interested as they felt
      information only caused more anxiety. CONCLUSIONS: Fever was often judged to
      cause discomfort and danger. Thus antipyretics like paracetamol were regarded as
      a medicine counteracting disease. Paracetamol constituted an important tool for
      parents in managing different upsets during childhood illnesses. Information was
      not always wanted. Better knowledge about the significance of fever and how to
      handle children during common illnesses might need to be presented in a context
      familiar to parents, for instance, in relation to general information on
      childcare.

PMID- 14701899
TI  - Who decides about prostate cancer treatment? A qualitative study.
AB  - BACKGROUND: Shared decision-making between patients and health professionals has
      been promoted as ethically and clinically desirable. Patients vary in their
      willingness to participate in decision-making, while clinicians identify
      practical barriers to greater participation, such as time and communication
      skills. A paternalistic approach to treatment decisions remains common even in an
      area of clinical uncertainty. The willingness of patients to participate in
      decision-making varies over time during the course of an illness but patients may
      not be given the opportunity to revisit clinical decisions with their specialists
      after the initial consultation. OBJECTIVES: To gain an in depth understanding of
      the perspectives of men recently diagnosed with localized prostate cancer, and to
      explore the value of decision-making models in the setting of NHS practice.
      METHODS: The study design was a qualitative analysis of semi-structured
      interviews. Nineteen men recently diagnosed with localized prostate cancer were
      included from patients attending a British District General Hospital. RESULTS:
      The interviews suggested that the respondents' treatment plans were mostly
      decided on their behalf by their clinicians. Whilst initially accepting this
      paternalistic approach, the interviewees over time wished to revisit the
      decisions. Patients' barriers to shared decision-making included fear of
      appearing disrespectful to their doctors and of taking responsibility for the
      outcome of treatment. The structure of patient follow-up did not afford the men
      an opportunity to discussion treatment decisions further. CONCLUSIONS: The
      paternalistic decision-making model remains the chosen approach in this
      situation. The patients' willingness to become actively involved in choosing
      their care varies over time. Barriers to shared decision-making can be identified
      both in the nature of the doctor-patient relationship and the structure of the
      clinical follow-up.

PMID- 14701900
TI  - Comparison of blood pressure measurements on the bare arm, below a rolled-up
      sleeve, or over a sleeve.
AB  - BACKGROUND: This study examined the effect of measuring blood pressure below
      subjects' rolled-up sleeves, over the sleeve, or on the bare arm. This is an
      important day-to-day issue for the busy GP. METHODS: The sample consisted of 201
      subjects in family practice clinics and residents of a senior citizens' home. A
      digital device was used in all cases. Each participant underwent three blood
      pressure measurements in each of the following conditions in random order: cuff
      on bare arm; cuff over the sleeve; and cuff below the rolled-up sleeve.
      Differences between measurements were plotted against the mean blood pressure.
      Confounding factors controlled for were age, sex, clothing pressure and skin-fold
      thickness. RESULTS: Differences in mean blood pressure readings between the
      clothed and bare arm were 0.5 mmHg (SD 7.5) for systolic pressure and 1 mmHg (SD
      5) for diastolic pressure; neither difference was significant. However, in
      hypertensive subjects (>140 mmHg systolic), although the mean difference remained
      small (systolic pressure, 2 mmHg, SD 10), the range of difference for individual
      subjects was -32 mmHg to +22 mmHg. CONCLUSION: The degree of clothing under the
      sphygmomanometer cuff does not have a clinically important effect on the blood
      pressure measurement. In patients known or found to be hypertensive, measurement
      on the bare arm is recommended.

PMID- 14701901
TI  - It is not parental choice.

PMID- 14701902
TI  - Hypertension in a primary care setting.

PMID- 14701903
TI  - Phylogenetic evidence for the early evolution of microcystin synthesis.
AB  - Cyanobacteria are a prolific source of secondary metabolites, including compounds
      with toxic and enzyme-inhibiting activities. Microcystins and nodularins are the
      end products of a secondary metabolic pathway comprised of mixed polyketide
      synthases and nonribosomal peptide synthetases. Both peptides are potent natural
      toxins produced by distantly related genera of cyanobacteria. Horizontal gene
      transfer is thought to play a role in the sporadic distribution of microcystin
      producers among cyanobacteria. Our phylogenetic analyses indicate a coevolution
      of housekeeping genes and microcystin synthetase genes for the entire
      evolutionary history of the toxin. Hence they do not corroborate horizontal
      transfer of genes for microcystin biosynthesis between the genera. The sporadic
      distribution of microcystin synthetase genes in modern cyanobacteria suggests
      that the ability to produce the toxin has been lost repeatedly in the more
      derived lineages of cyanobacteria. The data we present here strongly suggest that
      the genes encoding nodularin synthetase are recently derived from those encoding
      microcystin synthetase.

PMID- 14701904
TI  - Monitoring protein stability and aggregation in vivo by real-time fluorescent
      labeling.
AB  - In vivo fluorescent labeling of an expressed protein has enabled the observation
      of its stability and aggregation directly in bacterial cells. Mammalian cellular
      retinoic acid-binding protein I (CRABP I) was mutated to incorporate in a surface
      exposed omega loop the sequence Cys-Cys-Gly-Pro-Cys-Cys, which binds specifically
      to a biarsenical fluorescein dye (FlAsH). Unfolding of labeled tetra-Cys CRABP I
      is accompanied by enhancement of FlAsH fluorescence, which made it possible to
      determine the free energy of unfolding of this protein by urea titration in cells
      and to follow in real time the formation of inclusion bodies by a slow-folding,
      aggregationprone mutant (FlAsH-labeled P39A tetra-Cys CRABP I). Aggregation in
      vivo displayed a concentration-dependent apparent lag time similar to
      observations of protein aggregation in purified in vitro model systems.

PMID- 14701906
TI  - H-bonded N-heterocyclic base-pair phototautomerizational potential barrier and
      mechanism: The 7-azaindole dimer.
AB  - A theoretical analysis of the double proton transfer (PT) in a hydrogen-bonded N
      heterocyclic base pair is presented. The calculated (time-dependent density
      functional theory) double PT barrier calculated for the concerted process of the
      7-azaindole C(2h) dimer in the first excited singlet electronic state S(1)
      conforms well to the kinetic data and the photophysical evidence reported in this
      article. The calculated PT energy barrier of 4.8 kcal/mol height, and the
      corresponding zero point energy value, yield for the S(1) state an activation
      energy barrier of 0.3 kcal/mol. This finding implies that the double PT concerted
      process is almost barrierless, confirming previous experiments. Upon N-H
      deuteration of the 7-azaindole dimer, the theoretical excited-state activation
      energy for the double deuterium transfer is determined to be 1.4 kcal/mol, in
      agreement with experiment, which in low-temperature spectroscopy is shown to
      negate excited-state double-deuteron transfer.

PMID- 14701905
TI  - Identification of calcium- and nitric oxide-regulated genes by differential
      analysis of library expression (DAzLE).
AB  - Using a method of expression profiling called differential analysis of cDNA
      library expression (DAzLE), we report the expression profile of late response
      genes in a model of activity-dependent neuronal survival and neurite outgrowth.
      Using DAzLE, we isolated differentially expressed genes from cultured rat
      embryonic cortical neurons after KCl (50 mM)-mediated membrane depolarization. We
      identified 469 activity-dependent regulated genes, of which 174 are genes of
      unknown function. The regulation of 63 genes was found to be nitric oxide (NO)
      dependent. Identifiable genes fell into several major categories, including
      signal transduction pathways, neuronal development, DNA replication, gene
      transcription, protein metabolism, energy regulatory proteins, and antiapoptotic
      proteins. These genes may be important in activity-dependent neuron survival and
      development. Furthermore, these late response genes provide the tools to begin to
      investigate downstream events in activity-dependent neuronal survival and
      development. The major advantage of DAzLE is that it provides a nearly complete
      and relatively comprehensive differential screening profile that has the
      potential to be a powerful and useful tool in other fields of study.

PMID- 14701907
TI  - Enhanced hippocampal noradrenaline and serotonin release in galanin
      overexpressing mice after repeated forced swimming test.
AB  - Basal and forced swimming (FS) stress-induced release of noradrenaline (NA) and
      serotonin (5-HT) were determined by in vivo microdialysis in the ventral
      hippocampus of mice overexpressing galanin under the platelet-derived growth
      factor B promoter (GalOE/P) or under the dopamine beta-hydroxylase promoter
      (GalOE/D) (only NA). WT mice served as controls. Intraventricular infusion of
      galanin significantly reduced basal extracellular NA in WT mice and in GalOE/P
      mice (albeit less so). Microdialysis sampling during a 10-min FS showed that NA
      and 5-HT release were elevated to 213% and 156%, respectively, in the GalOE/P
      group, whereas in the WT group the increases were only 127% and 119%,
      respectively. The second (repeated) 10-min FS (RFS) caused a marked enhancement
      of NA and 5-HT release in the GalOE/P mice to 344% and 275%, respectively.
      However, the RFS caused only a 192% increase of extracellular NA levels in the
      GalOE/D mice. Pretreatment with the putative peptidergic galanin receptor
      antagonist M35 almost completely blocked the elevation of NA and 5-HT levels in
      the GalOE/P after RFS. These results suggest that the NA and 5-HT hippocampal
      afferents in GalOE/P mice are hypersensitive to both conditioned and
      unconditioned stressful stimuli, such as FS, and that this effect is mediated by
      galanin receptors. The present findings support a role of galanin in the
      regulation of release of NA and 5-HT, two neurotransmitters involved in mood
      control.

PMID- 14701908
TI  - Response of C3 and C4 plants to middle-Holocene climatic variation near the
      prairie-forest ecotone of Minnesota.
AB  - Paleorecords of the middle Holocene (MH) from the North American mid-continent
      can offer insights into ecological responses to pervasive drought that may
      accompany future climatic warming. We analyzed MH sediments from West Olaf Lake
      (WOL) and Steel Lake (SL) in Minnesota to examine the effects of warm/dry
      climatic conditions on prairie-woodland ecosystems. Mineral composition and
      carbonate delta(18)O were used to determine climatic variations, whereas pollen
      assemblages, charcoal delta(13)C, and charcoal accumulation rates were used to
      reconstruct vegetation composition, C(3) and C(4) plant abundance, and fire. The
      ratio of aragonite/calcite at WOL and delta(18)O at SL suggest that pronounced
      droughts occurred during the MH but that drought severity decreased with time.
      From charcoal delta(13)C data we estimated that the MH abundance of C(4) plants
      averaged 50% at WOL and 43% at SL. At WOL C(4) abundance was negatively
      correlated with aragonite/calcite, suggesting that severe moisture deficits
      suppressed C(4) plants in favor of weedy C(3) plants (e.g., Ambrosia). As climate
      ameliorated C(4) abundance increased (from approximately 33 to 66%) at the
      expense of weedy species, enhancing fuel availability and fire occurrence. In
      contrast, farther east at SL where climate was cooler and wetter, C(4) abundance
      showed no correlation with delta(18)O-inferred aridity. Woody C(3) plants (e.g.,
      Quercus) were more abundant, biomass flammability was lower, and fires were less
      important at SL than at WOL. Our results suggest that C(4) plants are adapted to
      warm/dry climatic conditions, but not to extreme droughts, and that the fire
      regime is controlled by biomass-climate interactions.

PMID- 14701909
TI  - Association of beta-catenin with the alpha-subunit of neuronal large-conductance
      Ca2+-activated K+ channels.
AB  - The association of Ca(2+)-activated K(+) channels with voltage-gated Ca(2+)
      channels at the presynaptic active zones of hair cells, photoreceptors, and
      neurons contributes to rapid repolarization of the membrane after excitation.
      Ca(2+) channels have been shown to bind to a large set of synaptic proteins, but
      the proteins interacting with Ca(2+)-activated K(+) channels remain unknown.
      Here, we report that the large-conductance Ca(2+)-activated K(+) channel of the
      chicken's cochlear hair cell interacts with beta-catenin. Yeast two-hybrid assays
      identified the S10 region of the K(+) channel's alpha-subunit and the ninth
      armadillo repeat and carboxyl terminus of beta-catenin as necessary for the
      interaction. An antiserum directed against the alpha-subunit specifically
      coprecipitated beta-catenin from brain synaptic proteins. beta-Catenin is known
      to associate with the synaptic protein Lin7/Velis/MALS, whose interaction partner
      Lin2/CASK also binds voltage-gated Ca(2+) channels. beta-Catenin may therefore
      provide a physical link between the two types of channels at the presynaptic
      active zone.

PMID- 14701910
TI  - Pattern of diversity in the genomic region near the maize domestication gene tb1.
AB  - Domesticated maize and its wild ancestor (teosinte) differ strikingly in
      morphology and afford an opportunity to examine the connection between strong
      selection and diversity in a major crop species. The tb1 gene largely controls
      the increase in apical dominance in maize relative to teosinte, and a region of
      the tb1 locus 5' to the transcript sequence was a target of selection during
      maize domestication. To better characterize the impact of selection at a major
      "domestication" locus, we have sequenced the upstream tb1 genomic region and
      systematically sampled nucleotide diversity for sites located as far as 163 kb
      upstream to tb1. Our analyses define a selective sweep of approximately 60-90 kb
      5' to the tb1 transcribed sequence. The selected region harbors a mixture of
      unique sequences and large repetitive elements, but it contains no predicted
      genes. Diversity at the nearest 5' gene to tb1 is typical of that for neutral
      maize loci, indicating that selection at tb1 has had a minimal impact on the
      surrounding chromosomal region. Our data also show low intergenic linkage
      disequilibrium in the region and suggest that selection has had a minor role in
      shaping the pattern of linkage disequilibrium that is observed. Finally, our data
      raise the possibility that maize-like tb1 haplotypes are present in extant
      teosinte populations, and our findings also suggest a model of tb1 gene
      regulation that differs from traditional views of how plant gene expression is
      controlled.

PMID- 14701911
TI  - Bacillus subtilis RecU protein cleaves Holliday junctions and anneals single
      stranded DNA.
AB  - Bacillus subtilis RecU protein is involved in homologous recombination, DNA
      repair, and chromosome segregation. Purified RecU binds preferentially to three-
      and four-strand junctions when compared to single-stranded DNA (ssDNA) and double
      stranded DNA (dsDNA) ( approximately 10- and approximately 40-fold lower
      efficiency, respectively). RecU cleaves mobile four-way junctions but fails to
      cleave a linear dsDNA with a putative cognate site, a finding consistent with a
      similar genetic defect observed for genes classified within the epsilon epistatic
      group (namely ruvA, recD, and recU). In the presence of Mg(2+), RecU also anneals
      a circular ssDNA and a homologous linear dsDNA with a ssDNA tail and a linear
      ssDNA and a homologous supercoiled dsDNA substrate. These results suggest that
      RecU, which cleaves recombination intermediates with high specificity, might also
      help in their assembly.

PMID- 14701912
TI  - Pseudomonas aeruginosa-plant root interactions. Pathogenicity, biofilm formation,
      and root exudation.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen capable of forming a
      biofilm under physiological conditions that contributes to its persistence
      despite long-term treatment with antibiotics. Here, we report that pathogenic P.
      aeruginosa strains PAO1 and PA14 are capable of infecting the roots of
      Arabidopsis and sweet basil (Ocimum basilicum), in vitro and in the soil, and are
      capable of causing plant mortality 7 d postinoculation. Before plant mortality,
      PAO1 and PA14 colonize the roots of Arabidopsis and sweet basil and form a
      biofilm as observed by scanning electron microscopy, phase contrast microscopy,
      and confocal scanning laser microscopy. Upon P. aeruginosa infection, sweet basil
      roots secrete rosmarinic acid (RA), a multifunctional caffeic acid ester that
      exhibits in vitro antibacterial activity against planktonic cells of both P.
      aeruginosa strains with a minimum inhibitory concentration of 3 microg mL(-1).
      However, in our studies RA did not attain minimum inhibitory concentration levels
      in sweet basil's root exudates before P. aeruginosa formed a biofilm that
      resisted the microbicidal effects of RA and ultimately caused plant mortality. We
      further demonstrated that P. aeruginosa biofilms were resistant to RA treatment
      under in vivo and in vitro conditions. In contrast, induction of RA secretion by
      sweet basil roots and exogenous supplementation of Arabidopsis root exudates with
      RA before infection conferred resistance to P. aeruginosa. Under the latter
      conditions, confocal scanning laser microscopy revealed large clusters of dead P.
      aeruginosa on the root surface of Arabidopsis and sweet basil, and biofilm
      formation was not observed. Studies with quorum-sensing mutants PAO210
      (DeltarhlI), PAO214 (DeltalasI), and PAO216 (DeltalasI DeltarhlI) demonstrated
      that all of the strains were pathogenic to Arabidopsis, which does not naturally
      secrete RA as a root exudate. However, PAO214 was the only pathogenic strain
      toward sweet basil, and PAO214 biofilm appeared comparable with biofilms formed
      by wild-type strains of P. aeruginosa. Our results collectively suggest that upon
      root colonization, P. aeruginosa forms a biofilm that confers resistance against
      root-secreted antibiotics.

PMID- 14701913
TI  - Ethylene-dependent and -independent processes associated with floral organ
      abscission in Arabidopsis.
AB  - Abscission is an important developmental process in the life cycle of the plant,
      regulating the detachment of organs from the main body of the plant. This
      mechanism can be initiated in response to environmental cues such as disease or
      pathogen, or it can be a programmed shedding of organs that no longer provide
      essential functions to the plant. We have identified five novel dab (delayed
      floral organ abscission) mutants (dab1-1, dab2-1, dab3-1, dab3-2, and dab3-3) in
      Arabidopsis. These mutants each display unique anatomical and physiological
      characteristics and are governed by three independent loci. Scanning electron
      microscopy shows delayed development of the flattened fracture plane in some
      mutants and irregular elongation in the cells of the fracture plane in other
      mutants. The anatomical observations are also supported by breakstrength
      measurements that show high breakstrength associated with broken cells, moderate
      levels for the flattened fracture plane, and low levels associated with the
      initial rounding of cells. In addition, observations on the expression patterns
      in the abscission zone of cell wall hydrolytic enzymes, chitinase and cellulose,
      show altered patterns in the mutants. Last, we have compared these mutants with
      the ethylene-insensitive mutants etr1-1 and ein2-1 to determine if ethylene is an
      essential component of the abscission process and find that although ethylene can
      accelerate abscission under many conditions, the perception of ethylene is not
      essential. The role of the dab genes and the ethylene response genes during the
      abscission process is discussed.

PMID- 14701915
TI  - Respiratory oxygen uptake is not decreased by an instantaneous elevation of
      [CO2], but is increased with long-term growth in the field at elevated [CO2].
AB  - Averaged across many previous investigations, doubling the CO2 concentration
      ([CO2]) has frequently been reported to cause an instantaneous reduction of leaf
      dark respiration measured as CO2 efflux. No known mechanism accounts for this
      effect, and four recent studies have shown that the measurement of respiratory
      CO2 efflux is prone to experimental artifacts that could account for the reported
      response. Here, these artifacts are avoided by use of a high-resolution dual
      channel oxygen analyzer within an open gas exchange system to measure respiratory
      O2 uptake in normal air. Leaf O2 uptake was determined in response to
      instantaneous elevation of [CO2] in nine contrasting species and to long-term
      elevation in seven species from four field experiments. Over six hundred separate
      measurements of respiration failed to reveal any decrease in respiratory O2
      uptake with an instantaneous increase in [CO2]. Respiration was found insensitive
      not only to doubling [CO2], but also to a 5-fold increase and to decrease to
      zero. Using a wide range of species and conditions, we confirm earlier reports
      that inhibition of respiration by instantaneous elevation of [CO2] is likely an
      experimental artifact. Instead of the expected decrease in respiration per unit
      leaf area in response to long-term growth in the field at elevated [CO2], there
      was a significant increase of 11% and 7% on an area and mass basis, respectively,
      averaged across all experiments. The findings suggest that leaf dark respiration
      will increase not decrease as atmospheric [CO2] rises.

PMID- 14701914
TI  - Transcriptional regulation of sorghum defense determinants against a phloem
      feeding aphid.
AB  - When attacked by a phloem-feeding greenbug aphid (Schizaphis graminum), sorghum
      (Sorghum bicolor) activates jasmonic acid (JA)- and salicylic acid (SA)-regulated
      genes, as well as genes outside known wounding and SA signaling pathways. A
      collection of 672 cDNAs was obtained by differential subtraction with cDNAs
      prepared from sorghum seedlings infested by greenbug aphids and those from
      uninfested seedlings. Subsequent expression profiling using DNA microarray and
      northern-blot analyses identified 82 transcript types from this collection
      responsive to greenbug feeding, methyl jasmonate (MeJA), or SA application. DNA
      sequencing analyses indicated that these encoded proteins functioning in direct
      defense, defense signaling, oxidative burst, secondary metabolism, abiotic
      stress, cell maintenance, and photosynthesis, as well as proteins of unknown
      function. In response to insect feeding, sorghum increased transcript abundance
      of numerous defense genes, with some SA-dependent pathogenesis-related genes
      responding to greenbug more strongly than to SA. In contrast, only weak induction
      of MeJA-regulated defense genes was observed after greenbug treatment. However,
      infestation tests confirmed that JA-regulated pathways were effective in plant
      defense against greenbugs. Activation of certain transcripts exclusively by
      greenbug infestation was observed, and may represent unique signal transduction
      events independent of JA- and SA-regulated pathways. Results indicate that plants
      coordinately regulate defense gene expression when attacked by phloem-feeding
      aphids, but also suggest that aphids are able to avoid triggering activation of
      some otherwise potentially effective plant defensive machinery, possibly through
      their particular mode of feeding.

PMID- 14701916
TI  - Hypobaric biology: Arabidopsis gene expression at low atmospheric pressure.
AB  - As a step in developing an understanding of plant adaptation to low atmospheric
      pressures, we have identified genes central to the initial response of
      Arabidopsis to hypobaria. Exposure of plants to an atmosphere of 10 kPa compared
      with the sea-level pressure of 101 kPa resulted in the significant differential
      expression of more than 200 genes between the two treatments. Less than one-half
      of the genes induced by hypobaria are similarly affected by hypoxia, suggesting
      that response to hypobaria is unique and is more complex than an adaptation to
      the reduced partial pressure of oxygen inherent to hypobaric environments. In
      addition, the suites of genes induced by hypobaria confirm that water movement is
      a paramount issue at low atmospheric pressures, because many of gene products
      intersect abscisic acid-related, drought-induced pathways. A motivational
      constituent of these experiments is the need to address the National Aeronautics
      and Space Administration's plans to include plants as integral components of
      advanced life support systems. The design of bioregenerative life support systems
      seeks to maximize productivity within structures engineered to minimize mass and
      resource consumption. Currently, there are severe limitations to producing Earth
      orbital, lunar, or Martian plant growth facilities that contain Earth-normal
      atmospheric pressures within light, transparent structures. However, some
      engineering limitations can be offset by growing plants in reduced atmospheric
      pressures. Characterization of the hypobaric response can therefore provide data
      to guide systems engineering development for bioregenerative life support, as
      well as lead to fundamental insights into aspects of desiccation metabolism and
      the means by which plants monitor water relations.

PMID- 14701917
TI  - The CesA gene family of barley. Quantitative analysis of transcripts reveals two
      groups of co-expressed genes.
AB  - Sequence data from cDNA and genomic clones, coupled with analyses of expressed
      sequence tag databases, indicate that the CesA (cellulose synthase) gene family
      from barley (Hordeum vulgare) has at least eight members, which are distributed
      across the genome. Quantitative polymerase chain reaction has been used to
      determine the relative abundance of mRNA transcripts for individual HvCesA genes
      in vegetative and floral tissues, at different stages of development. To ensure
      accurate expression profiling, geometric averaging of multiple internal control
      gene transcripts has been applied for the normalization of transcript abundance.
      Total HvCesA mRNA levels are highest in coleoptiles, roots, and stems and much
      lower in floral tissues, early developing grain, and in the elongation zone of
      leaves. In most tissues, HvCesA1, HvCesA2, and HvCesA6 predominate, and their
      relative abundance is very similar; these genes appear to be coordinately
      transcribed. A second group, comprising HvCesA4, HvCesA7, and HvCesA8, also
      appears to be coordinately transcribed, most obviously in maturing stem and root
      tissues. The HvCesA3 expression pattern does not fall into either of these two
      groups, and HvCesA5 transcript levels are extremely low in all tissues. Thus, the
      HvCesA genes fall into two general groups of three genes with respect to mRNA
      abundance, and the co-expression of the groups identifies their products as
      candidates for the rosettes that are involved in cellulose biosynthesis at the
      plasma membrane. Phylogenetic analysis allows the two groups of genes to be
      linked with orthologous Arabidopsis CesA genes that have been implicated in
      primary and secondary wall synthesis.

PMID- 14701919
TI  - Quantitative trait loci that determine lipoprotein cholesterol levels in an
      intercross of 129S1/SvImJ and CAST/Ei inbred mice.
AB  - To identify genetic determinants of lipoprotein levels, we are performing
      quantitative trait locus (QTL) analysis on a series of mouse intercrosses in a
      "daisy chain" experimental design, to increase the power of detecting QTL and to
      identify common variants that should segregate in multiple intercrosses. In this
      study, we intercrossed strains CAST/Ei and 129S1/SvImJ, determined HDL, total,
      and non-HDL cholesterol levels, and performed QTL mapping using Pseudomarker
      software. For HDL cholesterol, we identified two significant QTL on chromosome
      (Chr) 1 (Hdlq5, 82 cM, 60-100 cM) and Chr 4 (Hdlq10, 20 cM, 10-30 cM). For total
      cholesterol, we identified three significant QTL on Chr 1 (Chol7, 74 cM, 65-80
      cM), Chr 4 (Chol8, 12 cM, 0-30 cM), and Chr 17 (Chol9, 54 cM, 20-60 cM). For non
      HDL cholesterol, we identified significant QTL on Chr 8 (Nhdlq1, 34 cM, 20-60 cM)
      and Chr X (Nhdlq2, 6 cM, 0-18 cM). Hdlq10 was the only QTL detected in two
      intercrosses involving strain CAST/Ei. Hdlq5, Hdlq10, Nhdlq1, and two suggestive
      QTL at D7Mit246 and D15Mit115 coincided with orthologous human lipoprotein QTL.
      Our analysis furthers the knowledge of the genetic control of lipoprotein levels
      and points to the importance of Hdlq10, which was detected repeatedly in multiple
      studies.

PMID- 14701918
TI  - MUCILAGE-MODIFIED4 encodes a putative pectin biosynthetic enzyme developmentally
      regulated by APETALA2, TRANSPARENT TESTA GLABRA1, and GLABRA2 in the Arabidopsis
      seed coat.
AB  - The Arabidopsis seed coat epidermis undergoes a complex process of
      differentiation that includes the biosynthesis and secretion of large quantities
      of pectinaceous mucilage, cytoplasmic rearrangement, and secondary cell wall
      biosynthesis. Mutations in MUM4 (MUCILAGE-MODIFIED4) lead to a decrease in seed
      coat mucilage and incomplete cytoplasmic rearrangement. We show that MUM4 encodes
      a putative NDP-l-rhamnose synthase, an enzyme required for the synthesis of the
      pectin rhamnogalacturonan I, the major component of Arabidopsis mucilage. This
      result suggests that the synthesis of monosaccharide substrates is a limiting
      factor in the biosynthesis of pectinaceous seed coat mucilage. In addition, the
      reduced cytoplasmic rearrangement observed in the absence of a key enzyme in
      pectin biosynthesis in mum4 mutants establishes a causal link between mucilage
      production and cellular morphogenesis. The cellular phenotype seen in mum4
      mutants is similar to that of several transcription factors (AP2 [APETALA2], TTG1
      [TRANSPARENT TESTA GLABRA1], TTG2 MYB61, and GL2 [GLABRA2]). Expression studies
      suggest that MUM4 is developmentally regulated in the seed coat by AP2, TTG1, and
      GL2, whereas TTG2 and MYB61 appear to be regulating mucilage production through
      alternate pathway(s). Our results provide a framework for the regulation of
      mucilage production and secretory cell differentiation.

PMID- 14701920
TI  - Large-scale gene discovery in human airway epithelia reveals novel transcripts.
AB  - The airway epithelium represents an important barrier between the host and the
      environment. It is a first site of contact with pathogens, particulates, and
      other stimuli, and has evolved the means to dynamically respond to these
      challenges. In an effort to define the transcript profile of airway epithelia, we
      created and sequenced cDNA libraries from cystic fibrosis (CF) and non-CF
      epithelia and from human lung tissue. Sequencing of these libraries produced
      approximately 53,000 3'-expressed sequence tags (3'-ESTs). From these, a
      nonredundant UniGene set of more than 19,000 sequences was generated. Despite the
      relatively small contribution of airway epithelia to the total mass of the lung,
      focused gene discovery in this tissue yielded novel results. The ESTs included
      several thousand transcripts (6,416) not previously identified from cDNA
      sequences as expressed in the lung. Among the abundant transcripts were several
      genes involved in host defense. Most importantly, the set also included 879 3'
      ESTs that appear to be novel sequences not previously represented in the National
      Center for Biotechnology Information UniGene collection. This UniGene set should
      be useful for studies of pulmonary diseases involving the airway epithelium
      including cystic fibrosis, respiratory infections and asthma. It also provides a
      reagent for large-scale expression profiling.

PMID- 14701921
TI  - WAP1, a wheat APETALA1 homolog, plays a central role in the phase transition from
      vegetative to reproductive growth.
AB  - Heading time in bread wheat (Triticum aestivum L.) is determined by three
      characters: vernalization requirement, photoperiodic sensitivity and narrow-sense
      earliness, which are involved in the phase transition from vegetative to
      reproductive growth. We identified and characterized the APETALA1 (AP1)-like MADS
      box gene in wheat (WAP1) as an activator of phase transition. Its expression
      starts just before the phase transition and is maintained during the reproductive
      phase. Inhibition of WAP1 expression in the transgenic plants by co-suppression
      affected neither vernalization requirement nor photoperiodic sensitivity, but
      resulted in delayed narrow-sense earliness, indicating that WAP1 accelerates
      autonomous phase transition. Analyses of the WAP1 expression in the near-isogenic
      lines (NILs) for spring habit genes (Vrn) revealed that WAP1 transcripts were
      induced by vernalization strongly in the NILs with Vrn dominant alleles and
      weakly with the recessive alleles. Furthermore, WAP1 expression was up-regulated
      by a long photoperiod in both NILs with and those without a photoperiod
      insensitive gene (Ppd). These results suggest that WAP1 is a key gene in the
      regulatory pathway controlling the phase transition from vegetative to
      reproductive growth in wheat.

PMID- 14701922
TI  - The Arabidopsis-accelerated cell death gene ACD1 is involved in oxygenation of
      pheophorbide a: inhibition of the pheophorbide a oxygenase activity does not lead
      to the "stay-green" phenotype in Arabidopsis.
AB  - Oxygenation of pheophorbide a is a key step in chlorophyll breakdown. Several
      biochemical studies have implicated that this step was catalyzed by an iron
      containing and ferredoxin-dependent monooxygenase, pheophorbide a oxygenase
      (PaO). It has been proposed that inhibition of its activity arrests the
      chlorophyll breakdown and leads to the "stay-green" phenotype. We searched the
      Arabidopsis genome for a possible PaO-encoding gene and hypothesized that it has
      homology to known iron-containing Rieske-type monooxygenase sequences. We
      identified three such open reading frames, Tic55, ACD1 and ACD1-like. We produced
      transgenic Arabidopsis plants which expressed antisense RNA as a method to
      inhibit the expression of these genes. The appearance of these antisense plants
      were indistinguishable from that of the wild type under illumination. However,
      after they were kept under darkness for 5 d and again illuminated, the leaves of
      the antisense ACD1 plants (AsACD1) were bleached. Leaves of AsACD1 accumulated
      387 nmol (g FW)(-1) pheophorbide a which corresponded to 60% of chlorophyll a
      degraded. The rate of decrease in chlorophyll a was not influenced in senesced
      AsACD1 leaves. These results demonstrated that ACD1 is involved in PaO activity,
      and its inhibition led to photooxidative destruction of the cell instead of the
      "stay-green" phenotype.

PMID- 14701923
TI  - Functional differentiation of peroxisomes revealed by expression profiles of
      peroxisomal genes in Arabidopsis thaliana.
AB  - It is well known that peroxisomal matrix proteins contain one of two targeting
      signals, PTS1 and PTS2. We comprehensively surveyed genes related to peroxisomal
      function and biogenesis in the entire Arabidopsis genome sequence. Here, we
      identified 256 gene candidates of PTS1- and PTS2-containing proteins and another
      30 genes of non-PTS-containing proteins. Of these, only 29 proteins have been
      reported to be functionally characterized as peroxisomal proteins in higher
      plants. We extensively investigated expression profiles of genes described above
      in various organs of Arabidopsis: Statistical analyses of these expression
      profiles revealed that peroxisomal genes could be divided into five groups. One
      group showed ubiquitous expression in all organs examined, while the other four
      were classified as showing organ-specific expression in seedlings, cotyledons,
      roots and in both cotyledons and leaves. These data proposed more detailed
      description of differentiation of plant peroxisomes.

PMID- 14701924
TI  - Simultaneous measurement of stomatal conductance, non-photochemical quenching,
      and photochemical yield of photosystem II in intact leaves by thermal and
      chlorophyll fluorescence imaging.
AB  - A new imaging system capable of simultaneously measuring stomatal conductance and
      fluorescence parameters, non-photochemical quenching (NPQ) and photochemical
      yield of photosystem II (Phi(PSII)), in intact leaves under aerobic conditions by
      both thermal imaging and chlorophyll fluorescence imaging was developed. Changes
      in distributions of stomatal conductance and fluorescence parameters across
      Phaseolus vulgaris L. leaves induced by abscisic acid treatment were analyzed. A
      decrease in stomatal conductance expanded in all directions from the treatment
      site, then mainly spread along the lateral vein toward the leaf edge, depending
      on the ABA concentration gradient and the transpiration stream. The relationships
      between stomatal conductance and fluorescence parameters depended on the actinic
      light intensity, i.e. NPQ was greater and Phi(PSII) was lower at high light
      intensity. The fluorescence parameters did not change, regardless of stomatal
      closure levels at a photosynthetically active photon flux (PPF) of 270 micro mol
      m(-2) s(-1); however, they drastically changed at PPF values of 350 and 700 micro
      mol m(-2) s(-1), when the total stomatal conductance decreased to less than 80
      and 200 mmol m(-2) s(-1), respectively. This study has, for the first time,
      quantitatively analyzed relationships between spatiotemporal variations in
      stomatal conductance and fluorescence parameters in intact leaves under aerobic
      conditions.

PMID- 14701925
TI  - Isolation of an ozone-sensitive and jasmonate-semi-insensitive Arabidopsis mutant
      (oji1).
AB  - A novel ozone-sensitive mutant was isolated from Arabidopsis T-DNA tagging lines.
      This mutant revealed severe foliar injury and higher ethylene emission than the
      wild type under ozone exposure. The ozone-induced injury and ethylene emission
      were suppressed by pretreatment with aminoethoxyvinyl glycine, an inhibitor of
      ethylene biosynthesis, both in this mutant and wild-type plants. Pretreatment
      with methyl-jasmonate (MeJA) at 10 micro M, however, suppressed the ozone-induced
      ethylene emission and foliar injury only in the wild-type plants. This mutant was
      less sensitive to jasmonate than the wild type, estimated by the MeJA-induced
      inhibition of root elongation and ozone-induced expression of AtVSP1, a jasmonate
      inducible gene. Thus, this mutant was named oji1 (ozone-sensitive and jasmonate
      insensitive 1). These results suggest that the ozone sensitivity of oji1 is
      caused by the increase in ozone-induced emission of ethylene as a result of low
      sensitivity to jasmonate, which plays defensive roles under stress conditions.

PMID- 14701926
TI  - Partial conservation of LFY function between rice and Arabidopsis.
AB  - The LFY/FLO genes encode plant-specific transcription factors and play major
      roles in the reproductive transition as well as floral development. In this
      study, we reconstructed the phylogenetic tree of the 49 LFY/FLO homologs from
      various plant species. The tree clearly shows that the LFY/FLO genes from the
      eudicots and monocots formed the two monophyletic clusters with very high
      bootstrap probabilities, respectively. Furthermore, grass LFY/FLO genes have
      experienced significant acceleration of amino acid replacement rate compared with
      the eudicot homolog. To test whether grass LFY/FLO genes have a conserved
      function with those of eudicots, we introduced RFL, a rice LFY homolog, into the
      Arabidopsis lfy mutant. The RFL gene driven by LFY promoter partially rescued the
      lfy mutation, suggesting that the functions of LFY and RFL partly overlap.
      Interestingly, the RFL but not LFY, strongly activated the expression of AP1 and
      AG, the downstream targets of LFY, even in the vegetative tissues. The LFY::RFL
      transgenic Arabidopsis plants exhibited abnormal patterns of development such as
      leaf curling, bushy appearance and the transformation of ovules into carpels. All
      of the results indicate that both the partial conservation and divergence of LFY
      function between rice and Arabidopsis.

PMID- 14701927
TI  - Similar stress responses are elicited by copper and ultraviolet radiation in the
      aquatic plant Lemna gibba: implication of reactive oxygen species as common
      signals.
AB  - Metals and ultraviolet (UV) radiation are two environmental stressors that can
      cause damage to plants. These two types of stressors often impact simultaneously
      on plants and both are known to promote reactive oxygen species (ROS) production.
      However, little information is available on the potential parallel stress
      responses elicited by metals and UV radiation. Using the aquatic plant Lemna
      gibba, we found that copper and simulated solar radiation (SSR, a light source
      containing photosynthetically active radiation (PAR) and UV radiation) induced
      similar responses in the plants. Both copper and SSR caused ROS formation. The
      ROS levels were higher when copper was combined with SSR than when applied with
      PAR. Higher concentrations of copper plus PAR caused toxicity as monitored by
      diminished growth and chlorophyll content. This toxicity was more pronounced when
      copper was combined with SSR. Because the generation of ROS was also higher when
      copper was combined with SSR, we attributed this enhanced toxicity to elevated
      levels of ROS. In comparison to PAR-grown plants, SSR treated plants exhibited
      elevated levels of superoxide dismutase (SOD) and glutathione reductase (GR).
      These enzyme levels were further elevated under both PAR and SSR when copper was
      added at concentrations that generated ROS. Interestingly, copper treatment in
      the absence of SSR (i.e. copper plus PAR) induced synthesis of the same
      flavonoids as those observed in SSR without copper. Finally, addition of either
      dimethyl thiourea or GSH (two common ROS scavengers) lowered in vivo ROS
      production, alleviated toxicity and diminished induction of GR as well as
      accumulation of UV absorbing compounds. Thus, the potential of ROS being a common
      signal for acclimation to stress by both copper and UV can be considered.

PMID- 14701928
TI  - Photosynthetic enzyme accumulation during leaf development of Arundinella hirta,
      a C4 grass having Kranz cells not associated with veins.
AB  - The leaf of the NADP-malic enzyme type C(4) grass, Arundinella hirta, has not
      only mesophyll cells (MCs) and bundle sheath cells (BSCs, usual Kranz cells) but
      also another type of Kranz cells (distinctive cells; DCs) that are not associated
      with vascular bundles. We investigated photosynthetic enzyme accumulation along
      the base-to-tip maturation gradient of developing leaves by immunogold electron
      microscopy. In mature leaves, phosphoenolpyruvate carboxylase (PEPC) and ribulose
      1,5-bisphosphate carboxylase/oxygenase (Rubisco) were detected in the MC cytosol
      and in the BSC and DC chloroplasts, respectively. Pyruvate, P(i) dikinase (PPDK)
      was present in the chloroplasts of all photosynthetic cells but with higher
      levels in the MCs. Rubisco was first detected in the basal region of emerging
      leaf blades where the BSCs and DCs became discernable. Subsequently, the
      accumulation of PEPC and PPDK was initiated in the region where the granal
      proliferation in the chloroplasts was conspicuous; and, suberized lamellae were
      formed in the cell walls of the Kranz cells. There was no difference in the
      patterns of cellular development and enzyme accumulation between the BSCs and DCs
      or between the MCs adjacent to each type of Kranz cells. These results
      demonstrate that, although the DCs are not associated with veins, they behaved
      like BSCs with respect to enzyme induction and cellular differentiation.

PMID- 14701929
TI  - Molecular and biochemical analyses of OsRab7, a rice Rab7 homolog.
AB  - Rab7 is a small GTP-binding protein important in early to late endosome/lysosome
      vesicular transport in mammalian cells. We have isolated a Rab7 cDNA clone,
      OsRab7, from a cold-treated rice cDNA library by the subtraction screening
      method. The cDNA encodes a polypeptide of 206 amino acids with a calculated
      molecular mass of about 23 kDa. Its predicted amino acid sequence shows
      significantly high identity with the sequences of other Rab7 proteins. His-tagged
      OsRab7 bound to radiolabeled GTPgammaS in a specific and stoichiometric manner.
      Biochemical and structural properties of the Rab7 wild type (WT) protein were
      compared to those of Q67L and T22N mutants. The detergent 3-([3
      cholamidopropyl]dimethylammonio)-1-propane sulfonate (CHAPS) increased the
      guanine nucleotide binding and hydrolysis activities of Rab7WT. The OsRab7Q67L
      mutant showed much lower GTPase activity compared to the WT protein untreated
      with CHAPS, and the T22N mutant showed no GTP binding activity at all. The
      OsRab7Q67L mutant was constitutively active for guanine nucleotide binding while
      the T22N mutant (dominant negative) showed no guanine nucleotide binding
      activity. When bound to GTP, the Rab7WT and the Q67L mutants were protected from
      tryptic proteolysis. The cleavage pattern of the Rab7T22N mutant, however, was
      not affected by GTP addition. Northern and Western blot analyses suggested that
      OsRab7 is distributed in various tissues of rice. Furthermore, expression of a
      rice Rab7 gene was differentially regulated by various environmental stimuli such
      as cold, NaCl, dehydration, and ABA. In addition, subcellular localization of
      OsRab7 was investigated in the Arabidopsis protoplasts by a double-labeling
      experiment using GFP-fused OsRab7 and FM4-64. GFP-OsRab7 is localized to the
      vacuolar membrane, suggesting that OsRab7 is implicated in a vesicular transport
      to the vacuole in plant cells.

PMID- 14701930
TI  - HD-zip III homeobox genes that include a novel member, ZeHB-13 (Zinnia)/ATHB-15
      (Arabidopsis), are involved in procambium and xylem cell differentiation.
AB  - HD-Zip III homeobox genes are known to be essential transcriptional factors for
      vascular development. To further understand the relation of HD-Zip III genes in
      vascular differentiation, we isolated a new member of the HD-Zip III genes, ZeHB
      13, as a Zinnia homolog of ATHB-15, and then characterized the expression profile
      using a Zinnia xylogenic cell culture and Zinnia plants. We compared the
      accumulation pattern of transcripts for ZeHB-13 and other HD-Zip III genes and
      suggested that the expression of ZeHB-13 was restricted to the procambium and was
      not severely suppressed by brassinazole, an inhibitor of brassinosteroid
      biosynthesis, unlike other HD-Zip III genes. We also characterized its
      Arabidopsis counterpart, ATHB-15. A histochemical promoter analysis using ATHB
      15::GUS transgenic Arabidopsis plants indicated that ATHB-15 was active
      specifically in the procambium. These results strongly suggest that ZeHB-13/ATHB
      15 is a pivotal transcriptional regulator responsible for early vascular
      development. Based on these results, we will discuss the regulation of xylem
      development in light of the functions of HD-Zip III members and brassinosteroids.

PMID- 14701931
TI  - Expression of a bacterial xylose isomerase in potato tubers results in an altered
      hexose composition and a consequent induction of metabolism.
AB  - Here we investigate the role of hexoses in the metabolism of the developing
      potato (Solanum tuberosum) tuber by the expression of a bacterial xylose
      isomerase which catalyzes the interconversion of glucose and fructose.
      Previously, we found that glycolysis was induced in transgenic tubers expressing
      a yeast invertase in the cytosol and postulated that this was due either to the
      decreased levels of sucrose or to effects downstream of the sucrose cleavage. In
      the present study xylose isomerase was expressed under the control of the tuber
      specific patatin promoter. Selected transformants exhibited minor changes in the
      levels of tuber glucose and fructose but not in sucrose. Analysis of the enzyme
      activities of the glycolytic pathway revealed minor yet significant increases in
      the maximal catalytic activities of aldolase and glyceraldehyde 3-phosphate
      dehydrogenase but no increase in the activities of other enzymes of glycolysis.
      These lines were also characterized by an elevated tuber number, glycolytic and
      sucrose synthetic fluxes and in some metabolite levels downstream of glycolysis.
      When considered together these data suggest that the perturbation of hexose
      levels can result in increased glycolytic and sucrose (re)synthetic fluxes in the
      potato tuber even in the absence of changes in the level of sucrose. The
      consequences of altering hexose levels in the tuber are, however, not as severe
      as those observed following perturbation of the level of tuber sucrose.

PMID- 14701932
TI  - Increased stability of LHCII by aggregate formation during dark-induced leaf
      senescence in the Arabidopsis mutant, ore10.
AB  - Leaf senescence in a stay-green mutant of Arabidopsis thaliana, ore10, was
      investigated during dark-incubation of its detached leaves. During this dark
      induced senescence (DIS), Chl loss was delayed in ore10 mutants, as compared with
      wild type, but the rate of decline in the photochemical efficiency of PSII was
      not delayed in mutant leaves. After 2 d of DIS, native green gel electrophoresis
      of ore 10 leaf proteins resulted in a significant amount of pigment remaining as
      aggregates on top of the stacking gel. In addition, the accumulation of
      aggregates coincided with the emergence of a new band near 700 nm (F(699)) in the
      77 K fluorescence emission spectrum of the aggregates. At 4 d, F(699) became a
      major band, both in the isolated aggregates and in intact leaves. Prolonged
      treatment with detergents revealed that light-harvesting complex II (LHCII)
      remaining after 2 d was highly stable, and the accumulation of aggregates
      coincided with the appearance of truncated LHCII in senescing ore10 leaves. These
      results suggest that increased LHCII stability is due to the formation of
      aggregates of trimmed LHCII. Thus, the LHCII protein degradation step that
      follows proteolysis of its terminal peptides is a possible lesion site of the
      ore10 mutant.

PMID- 14701933
TI  - Over-expression of a barley aquaporin increased the shoot/root ratio and raised
      salt sensitivity in transgenic rice plants.
AB  - Barley HvPIP2;1 is a plasma membrane aquaporin and its expression was down
      regulated after salt stress in barley [Katsuhara et al. (2002) Plant Cell
      Physiol. 43: 885]. We produced and analyzed transgenic rice plants over
      expressing barley HvPIP2;1 in the present study. Over-expression of HvPIP2;1
      increased (1) radial hydraulic conductivity of roots (Lp(r)) to 140%, and (2) the
      mass ratio of shoot to root up to 150%. In these transgenic rice plants under
      salt stress of 100 mM NaCl, growth reduction was greater than in non-transgenic
      plants. A decrease in shoot water content (from 79% to 61%) and reduction of root
      mass or shoot mass (both less than 40% of non-stressed plants) were observed in
      transgenic plants under salt stress for 2 weeks. These results indicated that
      over-expression of HvPIP2;1 makes rice plants sensitive to 100 mM NaCl. The
      possible involvement of aquaporins in salt tolerance is discussed.

PMID- 14701934
TI  - Diurnal regulation of water transport and aquaporin gene expression in maize
      roots: contribution of PIP2 proteins.
AB  - In maize (Zea mays) roots, xylem water transfer supported by root pressure occurs
      during the day and is less important at night. Diurnal modifications of osmotic
      pressure gradient between medium and xylem could not explain the oscillation of
      water flux in young maize roots during the day-night cycle. We observed a high
      turgor pressure of root cortical cells associated with a high flux. In maize
      roots, ZmPIP transcripts oscillate during the day-night cycle exhibiting some
      characteristics of genes regulated by a circadian mechanism. The PIP protein
      level profile is different from the mRNA pattern. Moreover, ZmPIP1 and ZmPIP2
      protein levels are differentially regulated during the light and dark period and
      in response to continuous darkness suggesting different roles for both classes of
      PIP. Finally, our results suggest that aquaporins from ZmPIP2 subgroup may
      contribute to root water transfer by cellular pathway that occurs during the
      light and the dark period of the day-night cycle.

PMID- 14701935
TI  - Feedback regulation of the ammonium transporter gene family AMT1 by glutamine in
      rice.
AB  - The three members of the rice OsAMT1 gene family of ammonium transporters show
      distinct expression patterns; constitutive and ammonium-promoted expression in
      shoots and roots for OsAMT1;1; root-specific and ammonium-inducible expression
      for OsAMT1;2; root-specific and nitrogen-repressible expression for OsAMT1;3
      [Sonoda et al. (2003), Plant Cell Physiol. 44: 726]. To clarify the feedback
      mechanisms, and to identify regulatory factors of the OsAMT1 genes, the
      accumulation of the three mRNAs and its dependence on endogenous nitrogen
      compounds (as quantified by capillary electrophoresis) was studied. Ammonium
      application to roots following a period of nitrogen starvation induced
      accumulation of OsAMT1;1 and OsAMT1;2 mRNA, but a decrease of OsAMT1;3 mRNA
      levels. The expression patterns of the three genes showed good correlation
      (positive in OsAMT1;1 and OsAMT1;2, negative in OsAMT1;3) with the root tissue
      contents of glutamine but not of ammonium. The ammonium effects on OsAMT1
      expression were prevented by methionine sulfoximine, an inhibitor of glutamine
      synthetase. Moreover, glutamine had the same effect on transcriptional regulation
      of OsAMT1 genes as ammonium, indicating that glutamine rather than ammonium
      controls the expression of ammonium transporter genes in rice. These results
      imply that rice possesses unique mechanisms of adaptation to variable nitrogen
      sources in the soil.

PMID- 14701936
TI  - Systematic reverse genetic screening of T-DNA tagged genes in rice for functional
      genomic analyses: MADS-box genes as a test case.
AB  - We have generated 47 DNA pools and 235 subpools from 21,049 T-DNA insertion lines
      of rice. DNA pools of 500-1,000 lines were adequate for screening a T-DNA
      insertion within a 2-kb region. To examine the efficacy of the DNA pools, we
      selected MADS-box genes, which play an important role in controlling various
      aspects of plant development. A total of 34 MIKC-type MADS-box genes have now
      been identified from rice sequence databases. Our PCR screening for T-DNA
      insertions within 12 MADS-box genes resulted in the identification of five
      insertions in four different genes. These DNA pools will be valuable when
      isolating T-DNA insertional mutants in various rice genes. The DNA pool screening
      service and the mutant seeds are available upon request to genean@postech.ac.kr.

PMID- 14701937
TI  - Phytosulfokine stimulates somatic embryogenesis in Cryptomeria japonica.
AB  - Phytosulfokine (PSK), which has been identified as a plant growth factor, had a
      dramatic stimulatory effect on the formation of somatic embryos of sugi
      (Cryptomeria japonica) in the presence of polyethylene glycol. The resultant
      somatic embryos germinated with synchronous sprouting of cotyledons, hypocotyls
      and roots, and most of the seedlings grew normally. A cDNA clone for the
      precursor to the PSK peptide of C. japonica was identified in an expressed
      sequence tags database. Our results support the existence of a PSK signaling
      pathway in C. japonica.

PMID- 14701938
TI  - Heat-shock proteins 70 kDa and 19 kDa are not required for induction of
      embryogenesis of Brassica napus L. cv. topas microspores.
AB  - It is currently accepted that 'stress' triggers induction of microspore
      embryogenesis, and for Brassica napus L. cv. Topas it is heat-shock. It has been
      postulated that the heat-shock proteins (HSPs) generated during heat stress have
      a central role in the induction mechanism. To test this hypothesis we developed a
      microspore induction procedure, using colchicine instead of heat treatment. The
      level of HSP70 increased significantly during and following the microspore heat
      treatment while sHSP19 expression was induced at the onset of heat-shock and
      declined after 8 h. In contrast, induction of embryogenesis with colchicine was
      not accompanied by elevation of HSP70 nor by induction of sHSP19, indicating that
      these HSPs are not required for induction of microspore embryogensis in this
      model system. These data refute the current hypothesis that HSPs have an
      essential role in triggering microspore embryogenesis.

PMID- 14701939
TI  - Androgen regulates follicle-stimulating hormone beta gene expression in an
      activin-dependent manner in immortalized gonadotropes.
AB  - Little is known about the molecular mechanisms of androgen regulation of the
      FSHbeta gene; however, studies suggest that it consists of a complex feedback
      loop that involves multiple mechanisms acting at both the level of the
      hypothalamus and the pituitary. In the present study, we address androgen
      regulation of the FSHbeta gene in immortalized gonadotrope cells and investigate
      the roles of activin and GnRH in androgen action. Using transient transfection
      assays in the FSHbeta-expressing mouse gonadotrope cell line, LbetaT2, we
      demonstrate that androgens stimulate expression of an ovine FSHbeta reporter gene
      in a dose-dependent manner. Mutation of either of two conserved androgen response
      elements at -245/-231 and -153/-139 within the proximal region of the ovine
      FSHbeta gene promoter abolishes this stimulation, and androgen receptor binds
      directly to the -244 ARE in vitro. Androgen induction of the FSHbeta reporter
      gene is also dependent upon the activin autocrine loop present in the LbetaT2
      cells, as well as an activin-response element at -138/-124 of the FSHbeta gene.
      However, activin regulation of other genes remains unaffected by androgens. In
      addition, androgens stimulate expression of a mouse GnRH receptor reporter gene,
      and thus may indirectly augment the response of the FSHbeta gene to GnRH. Taken
      together, these data demonstrate that, in mouse gonadotropes, androgens act
      directly on the ovine FSHbeta gene to stimulate expression by a mechanism that is
      dependent upon activin, as well as acting indirectly, potentially through a
      second mechanism that may be dependent upon induction of GnRH receptor.

PMID- 14701940
TI  - Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle
      stimulating hormone beta subunit in mouse gonadotrope cells.
AB  - The activins are pleiotropic members of the TGFbeta superfamily. Within the
      anterior pituitary gland, activins stimulate FSH synthesis in an
      autocrine/paracrine fashion by stimulating transcription of the FSHbeta subunit
      gene. Here, the mechanisms mediating this effect were investigated in the murine
      gonadotrope cell line, LbetaT2. Recombinant activin A and activin B dose- and
      time-dependently stimulated endogenous FSHbeta mRNA expression. FSHbeta primary
      transcript and mRNA levels were increased within 30-60 min, but these effects
      were blocked by preincubation with the transcription inhibitor actinomycin-D,
      suggesting that the FSHbeta gene is a direct target of the activin signal
      transduction cascade. In other systems, activin signals are transduced through a
      heteromeric serine/threonine receptor complex, which includes the signaling
      activin type IB receptor [activin receptor-like kinase 4 (ALK4)]. Transfection of
      a constitutively active form of the receptor, ALK4T206D, stimulated FSHbeta mRNA
      levels. Overexpression of the inhibitory SMAD7 blocked this effect, as well as
      activin-stimulated FSHbeta transcription. Because SMAD7 functions by preventing
      access of SMAD2 and SMAD3 to ALK4, these data suggested that both activins and
      ALK4 require SMAD2 and/or SMAD3 to affect FSHbeta transcription. Consistent with
      this idea, activin A stimulated SMAD2 and SMAD3 phosphorylation and nuclear
      translocation within 5-10 min in LbetaT2 cells. Transient transfection of SMAD3,
      but not SMADs 1, 2, 4, 5, or 8, stimulated endogenous FSHbeta mRNA levels. The
      results of SMAD2 transfection studies were inconclusive, however, because of a
      persistent failure to overexpress the full-length SMAD2 protein specifically in
      LbetaT2 cells. To assess more directly roles for both SMAD2 and SMAD3 in activin
      stimulated FSHbeta expression, RNA interference was used to decrease endogenous
      SMAD protein levels in LbetaT2 cells. Activin A- and ALK4T206D-stimulated
      transcription of the FSHbeta gene were significantly attenuated by the depletion
      of either SMAD2 or SMAD3. Collectively, these data suggest that activins use both
      SMAD2- and SMAD3-dependent mechanisms to stimulate FSHbeta transcription in mouse
      gonadotrope cells.

PMID- 14701941
TI  - Granulosa cell-specific inactivation of follistatin causes female fertility
      defects.
AB  - Follistatin plays an important role in female physiology by regulating FSH levels
      through blocking activin actions. Failure to regulate FSH has been implicated as
      a potential cause of premature ovarian failure. Premature ovarian failure is
      characterized by amenorrhea, infertility, and elevated gonadotropin levels in
      women under the age of 40. Because follistatin is essential for postnatal
      viability, we designed a cre/loxP conditional knockout system to render the
      follistatin gene null specifically in the granulosa cells of the postnatal ovary
      using Amhr2cre transgenic mice. The follistatin conditional knockout females
      develop fertility defects, including reduced litter number and litter sizes and,
      in the most severe case, infertility. Reduced numbers of ovarian follicles,
      ovulation and fertilization defects, elevated levels of serum FSH and LH, and
      reduced levels of testosterone were observed in these mice. These findings
      demonstrate that compromising granulosa cell follistatin function leads to
      findings similar to those characterized in premature ovarian failure. Follistatin
      conditional knockouts may therefore be a useful model with which to further study
      this human syndrome. These studies are the first report of a granulosa cell
      specific deletion of a gene in the postnatal ovary and have important
      implications for future endeavors to generate ovary-specific knockout mouse
      models.

PMID- 14701942
TI  - Conserved transcriptional regulatory domains of the pdx-1 gene.
AB  - The pancreas and duodenum homeobox protein 1 (PDX-1) homeodomain-containing
      transcription factor affects both pancreatic endocrine cell development and adult
      islet beta-cell function. Cell-type-specific expression is controlled by
      sequences 5' flanking the pdx-1 gene transcription start site. One principal
      control region is located roughly between -2800 and -1600 bp and spans three
      conserved, distinct, and functionally important subdomains, termed areas I, II,
      and III. In this study, we found that an upstream control region in the rat pdx-1
      gene located between -6200 and -5670 bp is also present in the mouse, chicken,
      and human genes. This region is capable of independently directing pancreatic
      beta-cell-selective reporter gene expression and potentiating area I/II-driven
      activity. This newly recognized conserved subdomain has been termed area IV. The
      islet-enriched forkhead box A2 (FoxA2), NK2 homeobox 2.2 (Nkx2.2), and pancreas
      and duodenum homeobox protein 1 (PDX-1) transcription factors have been shown to
      activate area IV-driven reporter gene expression as well as bind to this region
      of the endogenous gene in beta-cells. Analysis of the histone H3 and H4
      acetylation level also indicated that areas I-IV are within transcriptionally
      active chromatin in beta-cells. Our data suggests that pdx-1 transcription is
      also regulated by factors acting upon conserved area IV sequences.

PMID- 14701944
TI  - Allergen specific immunotherapy in nasobronchial allergy.
AB  - BACKGROUND: More than one antigen has been used for immunotherapy of allergic
      disorders. So far less than five antigens have been employed with variable
      results. AIM: To evaluate effect of multiple antigens up to six in the
      immunotherapy of nasobronchial allergy. SETTING AND DESIGN: Based on clinical
      history, symptoms present for at least 3 years with set criteria of
      immunomodulation for asthma and rhinitis: documented IgE mediated asthma and
      rhinitis, failure in allergen avoidance and moderate to severe clinical
      manifestations. MATERIAL AND METHODS: Five hundred cases of various allergic
      disorders attending allergy clinic of Bombay hospital were screened. Allergen
      specific immunotherapy was initiated in 131 subjects (56 -rhinitis and 75 asthma)
      with prior consent. Patients suffering from allergic disorders secondary to
      diseases or drug therapy were excluded. Multiple allergen immunotherapy was given
      at specific intervals up to a period of one year. Allergen extracts were prepared
      as per standard technique. For statistical analysis "students't test" was used.
      RESULTS AND CONCLUSIONS: Significant improvement in PEFR, reduction in skin
      sensitivity to allergens used in immunotherapy formulation and symptomatic relief
      without any untoward reaction show that multiple allergen immunotherapy is as
      effective as monoallergen immunotherapy in nasobronchial allergy.

PMID- 14701943
TI  - Resistance of single-positive thymocytes to glucocorticoid-induced apoptosis is
      mediated by CD28 signaling.
AB  - Glucocorticoids administered in pharmacological doses potently induce apoptosis
      in immature double-positive thymocytes. In contrast, single-positive thymocytes
      are completely resistant. We now provide evidence that this difference can be
      attributed to CD28 signaling. When taken into culture, single-positive thymocytes
      also become sensitive to glucocorticoid-induced apoptosis, which can be prevented
      by enforced CD28 engagement using a novel type of antibody. This is achieved, at
      least in part, by transcriptional regulation of apoptosis-related genes such as
      Bcl-X(L) via a calcium- and phosphatidylinositol 3 kinase-dependent pathway.
      Accordingly, deficiency of CD28 in genetically engineered mice leads to an
      increased sensitivity of single-positive thymocytes toward glucocorticoid-induced
      cell death in vivo. Taken together, we have identified CD28 signaling in the
      thymus as a key player in determining the differential sensitivity of double
      positive and single-positive cells to glucocorticoid action.

PMID- 14701945
TI  - Absence of factor V Leiden (G1691A) mutation, FII G20210A allele in coronary
      artery disease in North India.
AB  - BACKGROUND: Interaction between various genetic and environmental factors is
      associated with coronary artery diseases (CADs). Factor V Leiden mutation (FVL)
      and FII G20210A polymorphism are two recently described genetic factors with a
      propensity towards venous thrombosis, however, with a doubtful role in coronary
      artery disease and myocardial infarction. AIM: Present study was conducted to
      assess the relationship of both these factors in coronary artery disease in
      population from North India. SETTING AND DESIGN: Case control study. MATERIAL AND
      METHODS: Two hundred angiographically proven coronary artery disease patients
      were studied to examine the association of Factor V Leiden mutation and FII
      G20210A mutation with coronary artery disease and myocardial infarction. Out of
      200 patients, 51 had myocardial infarction. Two hundred controls were selected
      who were from north India and were also age and sex matched. RESULTS AND
      CONCLUSIONS: Our results indicate that both these polymorphisms were totally
      absent in our population, therefore, these variants cannot be considered as
      independent risk factors or as a predictor for CAD. However, there is a need to
      confirm the above findings on patients from different populations from different
      parts of the country as there are reports which show that the incidence of Factor
      V Leiden varies from 1.3 % to 10%.

PMID- 14701946
TI  - Age dependency of serum insulin - like growth factor (IGF)-1 in healthy Turkish
      adolescents and adults.
AB  - BACKGROUND: Serum levels of insulin-like growth factor-1 (IGF-1) reflect
      endogenous growth hormone (GH) secretion in healthy subjects. Measurements of IGF
      1 are useful for diagnosis and follow-up of patients with acromegaly and the
      diagnosis of GH deficiency in children. AIMS: To assess age dependency and normal
      ranges of serum IGF-1 levels in healthy Turkish population. SETTING AND DESIGN:
      We therefore studied 272 healthy adolescents and adults between 15-75 years of
      age. None had diabetes or other endocrine disease or had received estrogen
      therapy. MATERIAL AND METHODS: Height, weight, body mass index (BMI) and waist
      hip ratio were measured in all subjects. Serum samples were obtained during
      morning hours and IGF-1 was measured by radioimmunoassay. STATISTICAL ANALYSIS:
      The age-dependent reference range for serum IGF-1 concentrations was calculated
      by simple least linear regression analysis: the regression line represents the
      means with 95 percent confidence intervals. Correlation analysis was also done.
      RESULTS: Ageing was negatively related to serum levels of IGF-1 (P= 0.0001, r=
      0.931) with a mean decrease (youngest vs. oldest). IGF-1 levels increased during
      adolescence, with the highest mean values during puberty. After puberty, a
      subsequent decline in serum levels of IGF-1 was apparent. There were also a
      significant difference according to gender; females had significantly higher
      levels (357.909+/-219.167 mg/L) than males (307.962+/-198.41 mg/L) (P=0.012). IGF
      1 levels were correlated with body height (P=0.001, r=0.223), body weight
      (P=0.002,r=-0.188) and BMI (P=0.039, r=0.128). CONCLUSION: IGF-1 serum levels
      increase in adolescents with a peak in puberty, whereafter IGF-1 levels return to
      prepubertal levels.

PMID- 14701947
TI  - Ciprofloxacin-tinidazole combination, fluconazole- azithromicin-secnidazole-kit
      and doxycycline- metronidazole combination therapy in syndromic management of
      pelvic inflammatory disease: a prospective randomized controlled trial.
AB  - BACKGROUND: Pelvic inflammatory disease is a common problem faced by the
      gynecologists in there out patient department. AIM: The aim of the study was to
      evaluate the efficacy of three treatment combinations in the syndromic management
      of pelvic inflammatory disease in the out patient setting. SETTING DESIGN: In the
      medical college hospital patients presenting in gynecology out patient department
      were enrolled. MATERIAL AND METHODS: One hundred and sixty five women with
      diagnosis of pelvic inflammatory disease were randomized into three equal groups
      getting ciprofloxacin (500 mg) and tinidazole (600 mg) combination twice daily
      for 7 days (Group 1), a kit containing fluconazole (150 mg), azithromycin (1 gm)
      and secnidazole (2 mg) as one time dose (Group 2) and Doxycycline 100mg twice
      daily and metronidazole 200 mg thrice daily for seven days (Group 3). Severity
      score was determined on first visit and after 1 week and 4 weeks when patients
      were called for follow up. STATISTICAL ANALYSIS: Chisqare test, Krusker wallis
      test and Mann Whitney test. RESULTS: There was significant reduction in severity
      score after 1 week of treatment, which was further reduced after 4 weeks in all
      the three groups. Cure rate was highest in-group 1 (96%) followed by group 2
      (93.5) and group 3 (91.3%) but the difference was not statistically significant.
      Resolution of inflammatory mass was highest in group 1. The incidence of side
      effects was highest and compliance was lowest in the doxycycline -metronidazole
      group, but the difference was not statistically significant. CONCLUSION: All the
      three treatment combinations were found to be equally effective in the syndromic
      management of pelvic inflammatory disease.

PMID- 14701948
TI  - Necrotizing myelitis in an immunocompetent child: a case report with review of
      literature.
AB  - A few cases of necrotizing myelitis have been reported in adults since its first
      description in 1973. No case has been described in the pediatric age group. A 12
      year-old boy, who presented with acute flaccid paraplegia, loss of sphincter
      control and sensory loss showed features suggestive of necrotizing myelitis on
      magnetic resonance imaging. Investigations carried out could not reveal a
      specific etiological or pre-disposing factor. No clinical improvement occurred
      despite the therapy.

PMID- 14701949
TI  - Venlafaxine withdrawal in organic anxiety disorder.

PMID- 14701950
TI  - What is the best way to implant a lens in an eye without adequate capsular
      support during a corneal transplantation?

PMID- 14701951
TI  - Keratitis due to a coelomycetous fungus: case reports and review of the
      literature.
AB  - PURPOSE: To describe a series of 7 patients with ulcerative keratitis caused by
      species of Colletotrichum, which are coelomycetous fungal pathogens. METHODS: The
      patients presented with keratitis of varying degrees of severity. Multiple
      scrapes from the corneal lesions of 6 of the 7 patients were used for
      microbiological investigations by a standard protocol. In the seventh patient,
      scraping was not performed due to the presence of deep infiltration and a
      descemetocele at presentation. All 7 patients were hospitalized and treatment was
      initiated with topical applications of natamycin (5%) and ciprofloxacin (0.3%)
      every hour and cyclopentolate (1%) drops 3 times daily. An emergency therapeutic
      penetrating keratoplasty was performed after 48 hours in the patient who had
      presented with a descemetocele and for another patient whose keratitis did not
      respond to 10 days of medical therapy. RESULTS: The corneal samples of all 7
      patients yielded significant growth of filamentous fungi in culture. On the basis
      of macroscopic and microscopic characteristics, the fungal isolates were
      identified as Colletotrichum spp. Corneal lesions completely resolved with
      medical therapy alone in 5 patients. In the 2 patients who had undergone
      therapeutic penetrating keratoplasty, the infection was eradicated and the
      corneal graft remained clear even after several months of follow-up. CONCLUSION:
      Colletotrichum spp may be more frequent causes of keratitis than previously
      thought. Keratitis due to Colletotrichum spp frequently responds to medical
      therapy alone, although surgery may be indicated in a small proportion of
      patients.

PMID- 14701952
TI  - Keratoconus--no association with the transforming growth factor beta-induced gene
      in a cohort of American patients.
AB  - PURPOSE: Keratoconus is a noninflammatory, corneal thinning disorder leading to
      mixed myopic and irregular astigmatism and implicated as a major reason for
      cornea transplantations in the Western world. Genetic factors have been suggested
      as a cause of keratoconus. The levels of transforming growth factor beta-induced
      (TGFBI) protein have been reported to be altered in keratoconus tissues.
      Mutations in this gene are responsible for causing various corneal dystrophies.
      Given this strong evidence of the involvement of this gene in corneal
      dystrophies, we investigated possible mutations within this gene in 15 probands
      of families with keratoconus. METHODS: All patients and control individuals had
      complete ophthalmological examination by a corneal specialist to determine their
      affectation status. The entire transcript of the TGFBI gene was analyzed by
      direct sequencing from patient DNA. RESULTS: We found 8 sequence variations
      within the gene, none of which was protein-altering changes. These changes were
      also observed in control individuals, and 4 are previously known polymorphisms.
      CONCLUSIONS: We concluded that the TGFBI gene is not responsible for causing
      keratoconus in these patients.

PMID- 14701953
TI  - Iris-sutured posterior chamber intraocular lens implantation during penetrating
      keratoplasty.
AB  - PURPOSE: To evaluate the clinical indications and postoperative results of iris
      sutured posterior chamber intraocular lens implants performed during penetrating
      keratoplasty. METHODS: Medical records were retrospectively reviewed for
      preoperative indications and postoperative results of 342 consecutive patients
      (366 eyes) who underwent iris suturing of a posterior chamber intraocular lens
      implant during penetrating keratoplasty over a 9-year period. RESULTS: Mean
      follow-up was 36 months. The principal indications for corneal transplantation
      were pseudophakic and aphakic bullous keratopathy. Mean postoperative best
      spectacle-corrected visual acuity was better than preoperatively at all measured
      time points (P < 0.0001) and improved from 20/474 preoperatively to 20/85 at 1
      year. Nine eyes (7.7%) with known preoperative glaucoma required escalation of
      therapy by medication or surgery to control the intraocular pressure. Seventy-two
      eyes (29%) without known preoperative glaucoma required treatment of elevated
      intraocular pressure. Seventy-nine eyes (28%) without known preoperative cystoid
      macular edema were additionally diagnosed. Mean endothelial cell counts declined
      throughout the study time frame. Corneal donor rejection episodes occurred in 36
      (9.8%) eyes, with the majority having a single episode. Overall, 27 (7.4%) eyes
      had known graft failure at last follow-up. Two eyes (0.5%) were enucleated
      following wound disruption. CONCLUSIONS: These long-term results of iris-sutured
      posterior chamber intraocular lens implants performed during penetrating
      keratoplasty suggest acceptable visual acuity, graft survival, and complication
      rates. They are similar to published retrospective and prospective results of
      flexible open-loop anterior chamber and transsclerally-sutured posterior chamber
      intraocular lens implants placed during penetrating keratoplasty.

PMID- 14701954
TI  - Corneal swelling with overnight wear of scleral contact lenses.
AB  - PURPOSE: The management of some ocular surface diseases may be enhanced by the
      overnight wear of a rigid gas-permeable (RGP) scleral contact lens (ScCL). There
      is little information of the hypoxic effect of extended RGP ScCL wear. The
      authors measured the corneal swelling after overnight wear of a rigid gas
      permeable scleral contact lens in normal subjects. METHODS: Four subjects wore an
      RGP ScCL overnight in 1 eye only on 4 occasions. The following morning the lens
      was removed immediately before optical pachymetry, and the corneal thicknesses of
      both eyes were measured by a masked observer. On another four occasions optical
      pachymetry was performed, but the lens was not worn the previous night. For each
      subject the lens was of the same thickness. Specular microscopy was used to
      estimate endothelial cell density. RESULTS: There were no adverse effects, and
      subjects reported no difficulties in handling the lenses. Overnight wear of ScCL
      induced a variable amount of corneal swelling among subjects from 4.9% to 17.5%.
      The overnight swelling correlated strongly with endothelial cell density.
      CONCLUSIONS: Overnight wear of ScCL caused an increased degree of corneal
      swelling compared with daytime wear. This degree of swelling should not rule out
      overnight therapeutic ScCL wear if the disease process is deemed to be more
      damaging than the hypoxic effect of an RGP ScCL worn overnight. However, when
      used for refractive correction, they should not be left in overnight.

PMID- 14701955
TI  - Corneal epithelial barrier function in diabetic patients.
AB  - PURPOSE: To evaluate the corneal epithelial barrier function in diabetic
      patients. METHODS: In 29 eyes of 29 diabetic patients and 55 eyes of 55
      nondiabetic controls, corneal epithelial permeability to fluorescein was measured
      using an anterior fluorophotometer. The average fluorescein concentration in the
      central cornea was compared between diabetic patients and controls. Multiple
      regression analysis was used to assess the factors that affect corneal epithelial
      barrier function in diabetic patients. RESULTS: The average fluorescein
      concentrations in diabetic patients and nondiabetic controls were 44.1 +/- 25.3
      ng/mL and 29.9 +/- 19.8 ng/mL (mean +/- SD), respectively (P = 0.0057, unpaired t
      test). An explanatory variable relevant to the impaired corneal epithelial
      barrier function was the serum hemoglobin A1c (HbA1c) concentration (standardized
      partial regression coefficient = 0.466, P = 0.0163). CONCLUSIONS: The corneal
      epithelial barrier function is impaired in diabetic patients. Diabetic patients
      with higher serum HbA1c levels are more predisposed to impaired barrier function
      in the corneal epithelium.

PMID- 14701956
TI  - Clinical and epidemiological advantages of culturing bacterial keratitis.
AB  - PURPOSE: To examine how the corneal culture result is associated with the
      antibacterial treatment response rate of ulcerative keratitis in a prospective
      cohort study and to determine whether culture confirmation affects the relative
      treatment effect in randomized clinical trials of bacterial keratitis. METHODS:
      The influence of a positive bacterial culture on the rates of antibacterial
      improvement and cure was estimated by proportional hazards regression among 608
      patients with ulcerative keratitis treated with topical ciprofloxacin
      monotherapy. The interaction of culture confirmation on the relative cure rates
      of 735 patients enrolled in 4 clinical trials comparing fluoroquinolone
      monotherapy to combined cephalosporin and aminoglycoside therapy was evaluated by
      metaregression. RESULTS: In a prospective cohort study, bacterial keratitis that
      was culture positive and longer than 4 mm had a 37% (95% confidence interval,
      20%, 51%) slower improvement rate and a 56% (95% confidence interval, 41%, 67%)
      slower cure rate during ciprofloxacin therapy. Among randomized clinical trials,
      the culture result did not modify the relative effect of treatments having
      similar 1-week cure rates. CONCLUSIONS: Culture confirmation affects the
      antibacterial therapeutic response rate of ulcerative keratitis and, while not
      modifying the comparative effect of equivalent antibacterial treatments,
      facilitates generalizability of clinical trials of bacterial keratitis.

PMID- 14701957
TI  - Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA
      treatment.
AB  - PURPOSE: Combined riboflavin/UVA treatment inducing collagen cross-links in the
      cornea has been shown to increase the biomechanical rigidity of the cornea and
      has been used successfully in the treatment of progressive keratoconus. The
      current study was undertaken to investigate the possible cytotoxic effect of
      combined riboflavin/UVA treatment on corneal keratocytes in vivo. METHODS: Thirty
      four New Zealand white rabbits were treated with 0.1% riboflavin solution and
      surface UVA irradiances ranging from 0.75 to 4 mW/cm2 (1.35- 7.2 J/cm2) for 30
      minutes. The animals were euthanized either 4 (n = 6) or 24 (n = 28) hours
      postoperatively. Four additional control eyes underwent epithelial debridement
      alone. The corneas of the enucleated eyes were evaluated in routine histologic
      sections. In addition, the TUNEL technique and transmission electron microscopy
      were used for the detection of keratocyte apoptosis. RESULTS: In the control eyes
      with corneal epithelial debridement only, apoptotic keratocytes were found in the
      anterior 50 microm of the corneal stroma 4 hours postoperatively. However,
      riboflavin/UVA-induced apoptosis was only visible in the rabbit eyes enucleated
      24 hours postoperatively. In these eyes, we found apoptosis of keratocytes down
      to a variable stromal depth depending on the applied UVA irradiance. A cytotoxic
      UVA irradiance for keratocytes in the range of 0.5-0.7 mW/cm2 could be deduced.
      CONCLUSIONS: Riboflavin/UVA treatment leads to a dose-dependent keratocyte damage
      that can be expected in human corneas down to a depth of 300 microm using a
      surface UVA dose of 5.4 J/cm2. Future studies should be done to examine the
      keratocyte repopulation and exclude possible adverse sequelae of keratocyte loss
      like stromal scarring or thinning.

PMID- 14701958
TI  - Q-switched erbium:YAG laser corneal trephination: thermal damage in corneal
      stroma and cut regularity of nonmechanical Q-switched erbium:YAG laser corneal
      trephination for penetrating keratoplasty.
AB  - PURPOSE: To assess stromal thermal damage and cut regularity induced by
      nonmechanical Q-switched Er:YAG laser corneal trephination for penetrating
      keratoplasty. METHODS: Corneal trephination was performed in 80 enucleated
      porcine eyes by Q-switched (2.94-microm) Er:YAG laser, along with donor and
      recipient masks made of metal or ceramic. All combinations of 0.65- or 0.96-mm
      spot diameter and 45- or 50-mJ/pulse energy setting were used with each of the
      masks at a 5-Hz repetition rate. Corneas were processed for histologic
      examinations. Stromal thermal damage was quantified on PAS-stained slides, and
      cut regularity was assessed semiquantitatively on a scale from 0 (regular) to 3
      (highly irregular). Transmission electron microscopy and scanning electron
      microscopy were performed on selected specimens. RESULTS: The least thermal
      damage (mean +/- SD = 6.2 +/- 0.7 microm) was found in the donor ceramic group
      with 50-mJ/pulse energy and 0.65-mm spot diameter, while the best regularity of
      the cut (1.2 +/- 0.4) was found in the donor ceramic group with 45-mJ pulse
      energy and 0.65-mm spot diameter. Thermal damage was less pronounced in donor
      than in recipient corneas (P < 0.01). Smaller spot diameter (0.65 mm) led to less
      thermal damage (P < 0.01) than the use of a 0.96-mm spot diameter. The
      differences in thermal damage between ceramic and metal masks were minimal.
      CONCLUSIONS: After Q-switched Er:YAG laser corneal trephination for nonmechanical
      penetrating keratoplasty, reproducible high cut regularity and low concomitant
      thermal damage were observed. This is an encouraging finding in the search for a
      nonmechanical trephine for penetrating keratoplasty combining high precision and
      low cost.

PMID- 14701959
TI  - Preparation and hydration control of corneal tissue strips for experimental use.
AB  - PURPOSE: The purpose of this study was to develop an experimental protocol to
      maintain corneal tissue strips at normal hydration and avoid swelling or
      dehydration during experimental studies on corneal biomechanics and thermal
      stability. METHODS: The corneal thickness of 9 whole Eye-Bank eyes was brought
      back to normal values by immersion in a 25% dextran solution for 24 hours.
      Corneal buttons were then removed and cut into 2 x 6 mm strips. The 9 strips were
      immersed successively in Dextran solutions at 25%, 22.5%, and 20% concentration
      at 35 degrees C. The thickness of the immersed strip in solution was measured
      every 5 minutes for 1 hour using a modified optical comparator. RESULTS: The mean
      final thickness for the nine corneal strips after one hour in 25%, 22.5%, and 20%
      dextran solution was 508 +/- 38, 563 +/- 56, and 592 +/- 33 microm, respectively.
      Average swelling in 25%, 22.5%, and 20% dextran solutions was 1.06 +/- 0.03, 1.20
      +/- 0.07, and 1.24 +/- 0.07 times the initial thickness, respectively.
      CONCLUSION: The hydration of corneal tissue strips is maintained at normal values
      when the strips are immersed in 25% Dextran solution. Corneal strips swell to
      thicknesses above normal values in solutions with lower molecular weights.

PMID- 14701960
TI  - Expression of p63 in pterygium and normal conjunctiva.
AB  - PURPOSE: The p63 gene has been identified as a marker of epithelial stem cells.
      Because pterygium may arise through an expansion of the proliferative capacity of
      the conjunctiva, we sought to document the expression of p63 in normal
      conjunctiva and pterygium specimens. METHODS: Immunostaining for p63 expression
      was performed on 10 pairs of pterygium and normal conjunctiva using a monoclonal
      antibody directed against human p63. RESULTS: Immunopositive reactions were seen
      in all samples. Levels of p63-positive cells were not statistically different
      between pterygium and normal conjunctivae (P = 0.7). CONCLUSION: These results
      strongly support previous studies that indicate that pterygium arises as a result
      of incorrect control of cellular apoptosis rather than from an increase in
      proliferative capacity.

PMID- 14701961
TI  - Combination of adult inclusion conjunctivitis and mucosa-associated lymphoid
      tissue (MALT) lymphoma in a young adult.
AB  - PURPOSE: To report a patient who was diagnosed with combined adult inclusion
      conjunctivitis (AIC) and mucosa-associated lymphoid tissue (MALT) lymphoma.
      METHODS: This is a case report. RESULTS: An 18-year-old male patient presented
      with chronic conjunctivitis and giant follicles. Evaluation by chlamydial antigen
      assay was positive. Conjunctival biopsy for the immunohistochemical stain and
      polymerase chain reaction of the left eye showed MALT lymphoma. CONCLUSIONS: MALT
      lymphoma can masquerade as other ocular surface diseases. Chlamydial infection
      causes chronic inflammation of the conjunctiva. Both of these diseases should be
      considered as a differential diagnosis of refractory follicular conjunctivitis.
      It is worthy of further study to determine whether chronic inflammation resulting
      from chlamydial infection increases the risk of MALT lymphoma or it is
      coincidental.

PMID- 14701962
TI  - Recurrent scleral abscess after uncomplicated cataract extraction.
AB  - PURPOSE: To report the unusual occurrence of a recurrent scleral abscess after
      uncomplicated cataract extraction. METHODS: Case report of a 77-year-old healthy
      woman. RESULTS: Multiple cultures and antibiotic treatments failed to resolve
      presenting symptoms. Gram stain, Gomori methenamine silver (GMS) stain, and all
      cultures were negative. After drainage of the abscess, the patient's symptoms
      cleared briefly, then returned 6 months later showing a positive GMS stain
      consistent with Candida. The patient was treated with amphotericin, natamycin,
      and fluconazole at this time, and a return in visual acuity occurred along with a
      resolution of symptoms. No re-occurrence has been noted with 2.5 years of follow
      up. CONCLUSIONS: Cataract extraction, although generally a safe procedure, can
      still result in unusual complications such as scleral abscesses. Excellent
      outcomes are possible once the infections are identified and treated.

PMID- 14701963
TI  - Fixed dilated pupil (Urrets-Zavalia syndrome) in corneal dystrophies.
AB  - PURPOSE: To report fixed dilated pupil following penetrating keratoplasty for
      corneal dystrophies. METHODS: Retrospective chart analysis of subjects who
      underwent penetrating keratoplasty for corneal dystrophies between 1998 and 2002
      at our institute. RESULTS: Three of the subjects with fixed dilated pupils after
      penetrating keratoplasty had Macular corneal dystrophy and one subject had Fuchs
      Endothelial dystrophy. Fixed dilated pupils were noticed in the immediate
      postoperative period. None of the subjects had evidence for glaucoma either pre-
      or postoperatively. The follow up period ranged from 5 to 18 months. CONCLUSIONS:
      Fixed dilated pupil (Urrets-Zavalia syndrome) can occur after penetrating
      keratoplasty for corneal dystrophies and may not be limited to eyes with
      keratoconus as previously reported.

PMID- 14701964
TI  - Spheroidal degeneration of the cornea: a clinicopathologic case report.
AB  - PURPOSE: To describe a case with clinicopathologic findings of spheroidal
      degeneration of the cornea in a 78-year-old man. METHODS: Description of the
      clinical features of 1 bilateral case with histopathologic findings from the
      penetrating keratoplasty specimen. RESULTS: Spheroidal degeneration of the cornea
      with histopathologic confirmation of extensive elastotic degeneration in anterior
      corneal stroma. CONCLUSIONS: The spheroidal degeneration in this patient was of
      visual significance. The history of repeated, extreme ultraviolet exposure during
      arc welding is believed to be the proximal cause of these corneal changes.

PMID- 14701965
TI  - A case of conjunctiva-cornea intraepithelial neoplasia successfully treated with
      topical mitomycin C and interferon alfa-2b in cycles.
AB  - PURPOSE: To report a case of conjunctiva-cornea intraepithelial neoplasia (CCIN)
      treated with topical mitomycin C (MMC) and interferon alfa-2b in cycles. METHODS:
      A 52-year-old woman referred for limbal stem cell deficiency and epithelial
      defect was found instead to have CCIN. The diagnosis was confirmed by impression
      cytology and treated in cycles with topical 0.02% MMC for 14 days in the first
      cycle, 12 days in the second cycle, and 3 days in the third cycle followed by
      topical interferon alfa-2b 1 x 106 U/mL for 11 days. RESULT: Topical MMC for 2.5
      cycles resulted in 95% reduction of CCIN and improvement of 2 lines of vision.
      Because of intolerance to MMC, she was switched to topical interferon alfa-2b for
      11 days, resulting in total resolution of CCIN, which lasted for at least 10
      months. CONCLUSIONS: After differentiation from a persistent corneal epithelial
      defect and limbal stem cell deficiency by dye staining and impression cytology,
      the patient in this case of CCIN was successfully treated with topical MMC and
      interferon alfa-2b in cycles.

PMID- 14701966
TI  - Keratoconus associated with hyperimmunoglobulin E syndrome.
AB  - PURPOSE: To report a case of keratoconus in a patient with hyper-IgE syndrome.
      METHODS: A case report of a 28-year-old man with hyperimmunoglobulin E syndrome
      (HIES) who presented with chronic eczematous dermatitis of the eyelids and severe
      eye itching. RESULTS: Best corrected visual acuity was 20/25 in the right eye and
      20/30 in the left eye. There was a scissoring reflex in both eyes with
      retinoscopy. Biomicroscopy of the cornea was normal, but corneal topography
      showed bilateral keratoconus. CONCLUSIONS: It is difficult to establish a direct
      correlation between keratoconus and HIES due to the rarity of the latter
      disorder. It is, however, important to consider this association and obtain a
      corneal topography to rule out corneal ectasia in patients with HIES.

PMID- 14701967
TI  - Ultrasound biomicroscopy in pigmented conjunctival cystic nevi.
AB  - PURPOSE: To report the use of ultrasound biomicroscopy in the clinical diagnosis
      and management of pigmented conjunctival cystic nevi. METHOD: Two patients, aged
      11 and 18 years, with rapidly growing raised conjunctival melanocytic lesions
      suspected to be inflamed juvenile conjunctival nevus underwent ultrasound
      biomicroscopic and histopathologic examinations. RESULTS: Ultrasound
      biomicroscopic examination of the lesions revealed multiple areas of cystic
      tissue, which is compatible with pathologic finding of compound nevus with
      epithelial inclusion cysts formation. Furthermore, clear interface was found
      between the mass and the underlying sclera. CONCLUSION: Pigmented conjunctival
      nevi may obscure cysts under slit-lamp examination. Ultrasound biomicroscopy is a
      useful diagnostic adjunct to distinguish cysts in conjunctival lesions.
      Additionally, this technique may be helpful in delineating the extent of lesions
      prior to excision biopsy.

PMID- 14701968
TI  - Bilateral keratoconjunctivitis associated with lichen planus.
AB  - PURPOSE: To describe a case of bilateral keratoconjunctivitis in a patient with
      lichen planus. METHODS: Case report and review of the English literature.
      RESULTS: To our knowledge, this is the fourth reported case of
      keratoconjunctivitis associated with lichen planus. A 33-year-old Navajo man with
      lichen planus had recurrent and progressive keratoconjunctivitis that failed to
      improve on multiple topical medications. Tapered oral prednisone, 2% topical
      cyclosporin, and amniotic membrane transplantation pacified the acute
      exacerbation. CONCLUSIONS: Our patient with lichen planus developed an ocular
      surface disease with cicatricial conjunctivitis, keratouveitis,
      keratoconjunctivitis sicca, punctate epithelial erosions, and persistent
      epithelial defects leading to noninfectious or infectious corneal ulceration.
      Amniotic membrane transplantation may play an adjunctive role in refractory cases
      of lichen planus-related keratoconjunctivitis. Topical cyclosporin may stabilize
      the ocular surface when combined with systemic immunosuppression in severe cases.

PMID- 14701969
TI  - Oral tetracyclines for ocular rosacea: an evidence-based review of the
      literature.
AB  - PURPOSE: To review the basis for the use of oral tetracyclines in ocular rosacea.
      METHODS: Review of the published literature. RESULTS: Two prospective, masked,
      and placebo-controlled studies of oxytetracycline for ocular rosacea demonstrated
      a modest treatment benefit. Studies performed with tetracycline and doxycycline
      for ocular rosacea were not placebo controlled, and the optimal drug, dose, and
      schedule of administration were not evaluated. CONCLUSIONS: Available evidence
      supports a moderate treatment benefit in ocular rosacea for oxytetracycline, a
      tetracycline derivative not currently available in the United States. The
      efficacies of doxycycline and tetracycline, including treatment effect, optimal
      dose, duration of therapy, and side effects when used for ocular rosacea have not
      been established.

PMID- 14701982
TI  - Comparison of the sensitivities of 5 different computed tomography scanners for
      the assessment of the progression of pulmonary emphysema: a phantom study.
AB  - RATIONALE AND OBJECTIVES: To compare the sensitivities of 5 different computed
      tomography scanners (4 multislice CT [MSCT] and 1 single-slice CT) in the
      assessment of the progression of pulmonary emphysema. METHODS: A Perspex cylinder
      phantom was constructed containing small pieces of polythene foam with densities
      representative of lung. Changing the cylinder's volume simulated subtle lung
      density changes. The sensitivity to density changes was defined by the variation
      in the residual errors from the linear regression line between time and density.
      RESULTS: The single-slice CT scanner was significantly less sensitive to density
      changes than MSCT scanners. Also, among MSCT scanners, small but significant
      differences were found when the standardized acquisition protocol was used.
      CONCLUSIONS: Considering the large sensitivity differences between single- and
      multislice CT scanners, we would recommended using MSCT scanners in clinical
      multicenter trials in emphysema. The protocol standardization of MSCT scanners
      can still be further improved.

PMID- 14701983
TI  - The clinical impact of camera-based positron emission tomography imaging in
      patients with recurrent colorectal cancer.
AB  - RATIONALE AND OBJECTIVES: F18-fluorodeoxyglucose (FDG)-positron emission
      tomography (PET) studies have clinical value in suspected recurrent or metastatic
      colorectal cancer cases. Because this modality is not accessible for many
      patients, a camera-based FDG (CB-FDG) coincidence imaging was suggested as an
      alternative. Although inferior in resolution to a dedicated PET system, it can
      make FDG studies available to more patients. We assessed the clinical value of CB
      FDG in patients with recurrent colorectal cancer. METHODS: The disease stage and
      treatment approach in 83 patients were twice determined by an oncologist and a
      surgeon, first based on the patient's records and blind to CB-FDG findings and
      then with the inclusion of FDG results in the decision-making analysis. RESULTS:
      On a lesion-based analysis, the sensitivity of CB-FDG was 95% and the specificity
      was 81% compared with 88% and 64%, respectively, for computed tomography. Adding
      FDG findings led to disease-stage alteration in 47 patients (57%), upstaging in
      35 (42%), and downstaging in 12 (15%). FDG localized the tumor sites in 21 of 26
      patients (81%) with suspected clinical recurrence and a negative conventional
      imaging workup. In 8 patients, FDG ruled out viable tumor tissue suggested by
      other modalities. The oncologist's suggested treatment approach was altered in
      54% of the patients and the surgeon altered the decision on operability in 28%.
      CONCLUSION: CB-FDG assessment has clinical value for both staging and selecting
      treatment in patients with recurrent colorectal cancer and can be considered an
      alternative to an nonaccessible dedicated PET system.

PMID- 14701984
TI  - Gauging effective spatial resolution in multirow helical cardiac computed
      tomography with a dynamic phantom.
AB  - PURPOSE: To devise a numerical indicator of image quality for multirow helical
      cardiac computed tomography (CT) and its relation to temporal resolution.
      MATERIALS AND METHODS: A pulsatile cardiac assist device was used to simulate
      cardiac wall motion by mechanically transmitting the device dynamics to a piece
      of tungsten wire. Wire motion induced by different device rates was captured with
      an 8-row subsecond helical CT scanner operating with various scanning parameters.
      Image artifacts were visually assessed and compared with the image point spread
      function (PSF) using the full width at half maximum (FWHM) area as a numerical
      estimate of spatial accuracy. RESULTS: At rest, the FWHM area was determined as
      1.3 mm2. At a device rate of 60 bpm, the FWHM area ranged from 1.51 mm2 to 21.62
      mm2, depending on the time of image reconstruction. Mean reproducibility of the
      FWHM area measurements was determined as 0.05, whereas visual estimates of motion
      artifact were highly variable between different readers (kappa = 0.19). Visually
      determined image quality correlated closely with the FWHM area metric (Spearman's
      rank correlation, P = 0.0001, rho = 0.841). At a device rate of 100 bpm, the
      minimum FWHM area was 2.00 mm2 using a single-sector algorithm, 1.41 mm2 using a
      2-segment algorithm, and 1.37 mm2 using a 4-segment algorithm. CONCLUSIONS: Use
      of a pulsatile cardiac assist device could serve as an in vitro test bed for
      cardiac CT imaging methods. Area FWHM of the PSF correlates well with visually
      determined image quality of a dynamic phantom, but provides better
      reproducibility than visual analysis.

PMID- 14701985
TI  - Aortoiliac enhancement during computed tomography angiography with reduced
      contrast material dose and saline solution flush: influence on magnitude and
      uniformity of the contrast column.
AB  - RATIONALE AND OBJECTIVES: To compare the magnitude and uniformity of aortoiliac
      contrast enhancement obtained from uniphasic contrast material injections versus
      contrast material injections with reduced iodine dose followed by a saline flush
      in aortoiliac multislice CT angiography (CTA). METHODS: Twenty-nine patients with
      abdominal aortic aneurysms underwent aortoiliac CTA using protocols A and B. With
      protocol A, 120 mL contrast material (300 mgI/mL), and with protocol B, 100 mL
      contrast material followed by a 40-mL saline solution flush were administered at
      a flow rate of 4 mL/s. Quantitative analysis was performed by calculating mean
      aortoiliac attenuation, mean plateau deviation, and mean difference between
      maximum and minimum attenuation value for both groups. Qualitative analysis was
      performed by visual assessment of vascular enhancement using 2-dimensional and 3
      dimensional postprocessing techniques. RESULTS: The mean aortoiliac attenuation
      with protocol A was 291 +/- 62 HU, and with protocol B it was 285 +/- 61 HU. The
      difference of 6 HU was not statistically significant (P = 0.27). Mean plateau
      deviation was significantly smaller using protocol A than protocol B (16 +/- 9 HU
      vs. 20 +/- 10 HU, P = 0.03). In addition, the mean difference between maximum and
      minimum attenuation value was significantly smaller with protocol A than with
      protocol B (59 +/- 29 HU vs. 72 +/- 32 HU, P = 0.01). Visual analysis showed no
      difference in contrast material magnitude and homogeneity between the protocols.
      CONCLUSIONS: In aortoiliac CTA, a saline solution flush after contrast material
      bolus allows an iodine dose reduction of approximately 20 mL without impairing
      the magnitude of contrast enhancement but degrades the uniformity of the contrast
      column. However, the degradation does not affect visual analysis.

PMID- 14701986
TI  - Coronary artery stents in multislice computed tomography: in vitro artifact
      evaluation.
AB  - RATIONALE AND OBJECTIVE: The aim of this study was to systematically compare the
      ability to assess the coronary artery lumen in the presence of coronary artery
      stents in multislice spiral CT (MSCT). METHODS: Ten different coronary artery
      stents were examined with 4- and 16-detector row MSCT scanners. For image
      reconstruction, a standard and a dedicated convolution kernel for coronary artery
      stent visualization were used. Images were analyzed regarding lumen visibility,
      intraluminal attenuation, and artifacts outside the stent lumen. Results were
      compared using repeated-measure analysis of variance. RESULTS: Depending on stent
      type, scanner hardware, and convolution kernel, artificial lumen narrowing ranged
      from 20% to 100%. The convolution kernel had the most significant influence on
      the visibility of the stent lumen. Artificial lumen narrowing and intraluminal
      attenuation changes decreased significantly using the dedicated convolution
      kernel. In general, most severe artifacts were caused by gold or gold-coated
      stents. CONCLUSIONS: Independent of the scanner hardware or dedicated convolution
      kernels, routine evaluation of most coronary artery stents is not yet feasible
      using MSCT.

PMID- 14701987
TI  - Dynamic magnetic resonance tomography and proton magnetic resonance spectroscopy
      of prostate cancers in rats treated by radiotherapy.
AB  - RATIONALE AND OBJECTIVES: To establish an experimental setting for monitoring
      perfusion and metabolism in orthotopic prostate cancer at 1.5 T using dynamic
      contrast-enhanced magnetic resonance imaging (DCE MRI) and 1H-MR spectroscopy
      (MRS). METHODS: Dunning rat prostate cancer cells were injected into the prostate
      by open surgery. Twelve tumor-bearing rats (5 of these irradiated) and 6 healthy
      controls were followed up using gadolinium-diethylenetriaminepentaacetic acid 
      enhanced dynamic MRI and 1H-MRS. Amplitude and the exchange rate constant kep
      were calculated (2-compartment model). From 1H-MR spectra, ratios of choline
      (Cho) and creatine (tCr) were calculated. All tumors were examined
      histologically. RESULTS: On DCE MRI parameter maps, tumors showed increased
      vascularization. kep and microvessel density were correlated (r = 0.97). Tumors
      showed elevated Cho/tCr and an unexpected lipid fraction (2.0-2.2 parts per
      million). Irradiation slowed tumor growth significantly. Changes of perfusion and
      metabolism could be detected in all tumors during follow up. CONCLUSION: DCE MRI
      and 1H-MRS has potential to characterize orthotopic Dunning prostate cancer in
      rats, which is a promising model similar to human prostate carcinomas.

PMID- 14701988
TI  - Relationship between cerebrospinal fluid and blood dynamics in healthy volunteers
      and patients with communicating hydrocephalus.
AB  - RATIONALE AND OBJECTIVES: Using magnetic resonance imaging (MRI), we investigated
      cerebral blood and cerebrospinal fluid (CSF) flows in patients with communicating
      hydrocephalus (CH) and in healthy volunteers to determine the contribution of CSF
      flow to brain pressure regulation in CH patients. METHODS: Cine phase-contrast
      MRI data from 16 healthy volunteers and 12 patients with CH characterized by
      hyperdynamic aqueductal CSF flow were analyzed using in-house image-processing
      software that automatically measured flow curves. Amplitude and temporal CSF and
      blood flow parameters were compared in the 2 groups. RESULTS: Jugular peak flow
      occurred significantly earlier (P < 0.01) in the CH patients than in the healthy
      volunteers. Cervical CSF oscillations were not significantly different between
      the 2 groups. CONCLUSION: Venous vessel compression and/or changes in
      intracranial subarachnoid CSF flow produce an increase in ventricular CSF flush
      that compensates for vascular brain expansion in patients with CH.

PMID- 14701989
TI  - Macrophage endocytosis of superparamagnetic iron oxide nanoparticles: mechanisms
      and comparison of ferumoxides and ferumoxtran-10.
AB  - RATIONALE AND OBJECTIVES: Superparamagnetic iron oxides (SPIO) used as magnetic
      resonance (MR) contrast agents undergo specific uptake by macrophages. The
      purpose of this study was first to determine the mechanism of macrophage uptake
      for Ferumoxides by using competition experiments with specific ligands of
      scavenger receptors SR-A (I/II) and second, to evaluate and compare the
      internalization of 2 different contrast agents, Ferumoxides (SPIO) and
      Ferumoxtran-10 (USPIO: ultrasmall superparamagnetic iron oxide) using macrophages
      obtained by chemical activation of human monocytic cells. METHODS: Ferumoxides
      and Ferumoxtran-10 are 2 MR contrast agents, composed of dextran-coated iron
      oxide nanoparticles. The endocytosis pathway of Ferumoxides was studied using
      competition experiments on mouse peritoneal macrophages in the presence of
      specific ligands of scavenger receptors SR-A (types I and II): polyinosinic acid
      and fucoidan. In vitro assays using THP-1 (human promonocyte) cells activated
      into macrophages were performed in the presence of the 2 superparamagnetic
      nanoparticles. The cellular uptake was determined by measuring the iron content
      using ICP-AES (inductively coupled plasma-atomic emission spectrometry) and by
      Prussian blue staining. RESULTS: In the presence of polyinosinic acid or
      fucoidan, the endocytosis of Ferumoxides by mouse peritoneal macrophages was
      inhibited. This inhibition was obtained using 10 microg/mL of scavenger receptor
      ligands at a concentration of 62.5 microg Fe/mL of SPIO, and a dose-dependent
      relationship was observed. Without competitors, the percentage of uptake of
      Ferumoxides by mouse peritoneal macrophages ranged between 3 and 8%. On the human
      activated monocyte THP-1 cell assay, Ferumoxides underwent a higher macrophage
      uptake (between 1.1 and 3%) compared with Ferumoxtran-10 (between 0.03 and
      0.12%). This difference is attributed to the larger size of Ferumoxides
      nanoparticles. CONCLUSIONS: Competition experiments indicate that the cellular
      uptake of Ferumoxides involves scavenger receptor SR-A-mediated endocytosis. The
      comparison between Ferumoxides and Ferumoxtran-10 confirms that macrophage uptake
      of iron oxide nanoparticles depends mainly on the size of these contrast agents.

PMID- 14701990
TI  - The necessity for sphenoidal electrodes in the presurgical evaluation of temporal
      lobe epilepsy: pro position.
AB  - Whether sphenoidal electrodes should be used in the presurgical evaluation of
      people with refractory epilepsy has remained controversial. Many studies have
      been published touting their advantages, or conversely, their lack of benefit.
      The present paper reviews the evidence supporting the utility of sphenoidal
      electrodes. In principle, sphenoidal electrodes have an advantage over laterally
      placed scalp electrodes in detecting inferiorly directed mesial temporal
      discharges. Published studies demonstrate that sphenoidal electrodes are more
      sensitive than scalp electrodes and sometimes detect interictal spikes and
      seizures not seen with scalp electrodes. While the net added yield is relatively
      low, perhaps 5 to 10%, those patients in whom sphenoidal electrodes provide
      unique localizing information have much to gain. Sphenoidal electrodes may spare
      some patients unnecessary intracranial electrode investigation and permit surgery
      for others.

PMID- 14701991
TI  - The necessity for sphenoidal electrodes in the presurgical evaluation of temporal
      lobe epilepsy: con position.
AB  - This article reviews several lines of evidence that efface the requirement for
      sphenoidal leads in the EEG investigation of temporal lobe epilepsy. Mandibular
      notch or anterior temporal electrodes, each situated well within the anterior
      temporal spike field, detect interictal and ictal epileptiform phenomena
      virtually as well as do sphenoidal leads, provide consistent recording
      circumstances, do not require physician expertise for their placement, and create
      no discomfort. This article also cites many studies demonstrating the reliability
      of ictal semeiology and of MRI in lateralizing and localizing temporal
      epileptogenesis. Thus, EEG constitutes one element in a matrix of lateralizing
      data.

PMID- 14701992
TI  - Propagation of interictal epileptiform activity can lead to erroneous source
      localizations: a 128-channel EEG mapping study.
AB  - The relationship between interictal epileptiform activity and the epileptogenic
      zone is complex. Despite the fact that intraspike propagation may occur, the peak
      of the spike is often used as indicator of the site of ictal onset. In this
      investigation, spatio-temporal segmentation was used to demonstrate this
      intraspike propagation and to determine at which time point the voltage pattern
      corresponded best to the epileptogenic zone. Sixteen patients with focal epilepsy
      were recorded with 125-channel EEG. Between one and five different map
      topographies were identified during the rising phase of the spike. A distributed
      source model (EPIFOCUS) was used to localize the source of each map, and the
      distance from the EPIFOCUS maximum to the anatomic lesion was calculated. In only
      3 of 16 cases was the entire rising phase of the spike accounted for by one
      single map. In another five patients, several maps were obtained, although all
      were located within the epileptogenic lesion. In the remaining eight patients,
      however, parts of the rising phase had locations outside the epileptogenic
      lesion. On the average, 80% of the rising time had within lesion locations the
      most reliable time period being halfway between onset and peak. The results
      illustrate that intraspike propagation has to be considered in source
      localizations, and they also illustrate the usefulness of spatio-temporal
      segmentation for visualizing this propagation.

PMID- 14701993
TI  - Nearest neighbor phase synchronization as a measure to detect seizure activity
      from scalp EEG recordings.
AB  - The author presents results from the application of a particular measure for
      synchronization between brain areas (i.e., phase synchronization) in its behavior
      to detect epileptic seizure activity from scalp EEG recordings. The primary
      motivation for the current study was to contribute to the development of
      physiologic measures that both transform the EEG to a visual domain that allows a
      more intuitive interpretation of the interictal and ictal EEG and allows
      automated analysis, both relevant for real-time monitoring. EEGs from 16 patients
      experiencing temporal lobe and generalized seizures were analyzed. Nearest
      neighbor phase synchronization (NNPS) values for several frequency bands were
      determined. Additional analysis of the NNPS in the delta band, using different
      thresholds, allows construction of receiver operating characteristics (ROC)
      curves for each EEG analyzed. The common value for the sensitivity and the
      specificity, Q*, was used as a measure for the test accuracy, with values of Q*
      near 1.0, indicating ROC curves with sensitivity and specificity both approaching
      1.0. It was found that Q* = 0.48 to 0.87, depending on the EEG analyzed,
      indicating that the proposed method allows seizure detection in a significant
      portion of the EEGs studied. Nearest neighbor phase synchronization was typically
      increased during seizure activity and seems to be a promising method to detect
      seizure activity from scalp EEG recordings. The proposed visualization allows an
      intuitive interpretation of the EEG and may assist in real-time monitoring.

PMID- 14701994
TI  - Estimation of active cortical current source regions using a vector
      representation scanning approach.
AB  - The objective of this article is to present a framework for cortical current
      source reconstruction that extracts a center and magnitude of electrical brain
      activity from EEG signals. High-resolution EEG recordings, a subject-specific MRI
      based electromagnetic boundary element method (BEM) model, and a channel
      reduction technique are used. This new geometric measure combines the magnitude
      and spatial location of electrical brain activity of each of the identified
      subsets of channels into a three-dimensional resultant vector. The combination of
      the two approaches constitutes a source reconstruction scanning technique that
      provides a real-time estimation of cortical centers that can be tracked over
      time. Simulations demonstrate that the ability of this method to find the best
      fit cortical location is more robust both in terms of accuracy and precision than
      traditional approaches for single-source conditions. Experimental validation
      demonstrates its ability to localize and separate cortical activity in plausible
      sites for two different motor tasks. Finally, this method provides a statistical
      measure to compare electrical brain activity associated with different motor
      tasks.

PMID- 14701995
TI  - Wicket spikes during rapid eye movement sleep.
AB  - Wicket spikes correspond to a normal variant activity. They usually occur in
      adults over 50 years of age during drowsiness and light nonrapid eye movement
      (NREM) sleep. No data exist in the precise distribution of this activity during
      all the different sleep stages, particularly during rapid eye movement (REM)
      sleep. The authors report five observations of persistence of this activity
      during REM sleep. Only one patient was over 50 years of age. The authors found a
      predominant expression on one temporal side, but inconsistently on the left side
      (three on the left side versus two on the right side). Wicket spikes always
      persist in REM sleep. They have an identical morphology as drowsiness or stage 2
      sleep. There were no changes in their location. The authors found no correlation
      with the tonic or phasic phases of REM sleep.

PMID- 14701996
TI  - Event-related potentials in the frontal lobe during performance of a visual
      duration discrimination task.
AB  - An event-related potential (ERP) study was conducted to elucidate the role of the
      prefrontal cortex (PFC) in time estimation. Subjects discriminated between three
      pairs of visual stimuli lasting from 100 ms and 2 seconds by determining whether
      the second stimulus was longer or briefer than the first. Event-related
      potentials were recorded in frontal and prefrontal regions after offset of the
      second stimulus (S2). The results indicated that the accuracy of the performances
      depended on stimulus duration and presentation order. In the brief-long order,
      the number of successful responses was higher as a function of stimulus duration.
      A time-related late positive component (LPCt) was revealed at prefrontal and
      frontal electrodes whose latency and amplitude differed depending on stimulus
      duration and order. The amplitude of this positive wave was higher when
      performance levels increased in the brief-long but not the reverse order. These
      results indicate that the LPCt may reflect successful decision-making or
      retrieval during time estimation as a result of neuronal activity in the PFC.

PMID- 14701997
TI  - The effects of pulse configuration on magnetic stimulation.
AB  - A study is presented in which the authors have examined the effects of pulse
      configuration, stimulation intensity, and coil current direction during magnetic
      stimulation. Using figure-8 and circular coils, the median nerve was stimulated
      at the cubital fossa and at the wrist of 10 healthy volunteers, and the response
      amplitude and site of stimulation were determined. The key findings of this study
      are in agreement with other researchers' findings and confirm that biphasic
      stimulating pulses produce significantly higher M-wave amplitudes than monophasic
      stimulating pulses for the same stimulus intensity. Mean response amplitudes for
      biphasic stimuli applied by both coils at the elbow and wrist are consistently
      higher for the normal current direction. Mean response amplitudes for monophasic
      pulses are almost always higher for reversed currents. The site for effective
      stimulation (the position of the virtual cathode) cannot be defined within a
      fixed distance from the center of the coil (3 to 4 cm), as has been suggested by
      other researchers, but was found to vary depending on the coil current amplitude
      and direction as well as the degree of inhomogeneity of the tissues surrounding
      the nerve. There is a statistically significant relationship between virtual
      cathode shift and stimulus intensity for biphasic and monophasic pulses.
      Reversing the coil current direction has no statistically significant effect on
      the virtual cathode position. Virtual cathode shifts can be measured for biphasic
      and monophasic stimulations using a figure-8 coil at the wrist and the elbow.
      However, such a shift is difficult to determine with a circular coil.

PMID- 14701998
TI  - Paired-pulse transcranial magnetic stimulation: effects of hemispheric
      laterality, gender, and handedness in normal controls.
AB  - This investigation analyzed retrospective normative data from paired-pulse
      transcranial magnetic stimulation (PP TMS) studies to assess the effects of
      hemispheric laterality, gender, and handedness on cortical excitability. There
      were no significant differences between left and right hemisphere responses in
      either men or women. Likewise, there was no significant difference in findings
      between men and women, considering each hemisphere separately. There were no
      significant differences between right-handed individuals and nonright-handed
      individuals for left or right hemispheric responses in either men or women or for
      both genders combined. Nevertheless, large intersubject variance and past
      evidence of cortical excitability modulation by other factors, such as menstrual
      cycle phase and reproductive hormonal changes in women, suggest a need for
      further investigations into other potential factors that may contribute to the
      large variance among healthy individuals.

PMID- 14701999
TI  - Changes in pattern electroretinograms to equiluminant red-green and blue-yellow
      gratings in patients with early Parkinson's disease.
AB  - In Parkinson's disease (PD), the luminance pattern electroretinogram (PERG) is
      reported to be abnormal, indicating dysfunction of retinal ganglion cells (RGCs).
      To determine the vulnerability of different subpopulations of RGCs in PD
      patients, the authors recorded the PERG to stimuli of chromatic (red-green [R-G]
      and blue-yellow [B-Y]) and achromatic (yellow-black [Y-Bk]) contrast, known to
      emphasize the contribution of parvocellular, koniocellular, and magnocellular
      RGCs, respectively. Subjects were early PD patients (n = 12; mean age, 60.1 +/-
      8.3 years; range, 46 to 74 years) not undergoing treatment with levodopa and age
      sex-matched controls (n = 12). Pattern electroretinograms were recorded
      monocularly in response to equiluminant R-G, B-Y, and Y-Bk horizontal gratings of
      0.3 c/deg and 90% contrast, reversed at 1Hz, and presented at a viewing distance
      of 24 cm (59.2 x 59 degree field). In PD patients, the PERG amplitude was
      significantly reduced (by 40 to 50% on average) for both chromatic and luminance
      stimuli. Pattern electroretinogram latency was significantly delayed (by about 15
      ms) for B-Y stimuli only. Data indicate that, in addition to achromatic PERGs,
      chromatic PERGs are altered in PD before levodopa therapy. Overall, chromatic
      PERGs to B-Y equiluminant stimuli exhibited the largest changes. Data are
      consistent with previous findings in PD, showing that visual evoked potentials
      (VEP) to B-Y chromatic stimuli are more delayed than VEPs to R-G and achromatic
      stimuli. The results suggest that the koniocellular subpopulation of RGCs may be
      particularly vulnerable in early stages of Parkinson's disease.

PMID- 14702000
TI  - Single fiber EMG as an outcome measure in myasthenia gravis: results from a
      double-blind, placebo-controlled trial.
AB  - In a placebo-controlled, therapeutic, pilot trial of mycophenolate mofetil (MM)
      in autoimmune myasthenia gravis (MG), the authors compared pretreatment and
      posttreatment single fiber electromyography (SFEMG) jitter measurements performed
      on the same muscle in a total of 11 patients. The mean jitter value decreased
      (improved) by an average of 15.4 micros in patients receiving MM (n = 6),
      compared to an increase (worsening) in mean jitter of 4.0 micros in patients
      receiving placebo (n = 5). This difference was statistically significant (P =
      0.030). In most patients, the change in SFEMG measurements correlated with the
      change in clinical state as measured by quantitative testing of muscle function.
      The authors conclude that immunomodulation by MM improves neuromuscular junction
      function in MG and that SFEMG may be a useful marker of early response in future
      therapeutic trials in autoimmune MG.

PMID- 14702001
TI  - Untangling Alzheimer's disease.

PMID- 14702002
TI  - New findings, new thinking, and new expectations in Alzheimer's disease.

PMID- 14702003
TI  - Emergent oscillations in a mathematical model of the human menstrual cycle.
AB  - BACKGROUND: The aim of this study was to develop a mathematical model of the
      hypothalamo-pituitary-gonadal axis that would reflect available data in humans.
      METHODS: A model of hormonal relationships at the early follicular and midluteal
      phases of the human menstrual cycle is proposed. FINDINGS: Two distinct temporal
      patterns of oscillatory behavior have been demonstrated for both pituitary and
      gonadal steroids in the early follicular phase: first, rapid oscillations in
      gonadotropin releasing hormone, follicle stimulating hormone and luteinizing
      hormone (Q approximate to 1 hour) that were an immediate consequence of the
      programmed equations. Second, there were slower, undulating, emergent rhythms in
      luteinizing hormone and follicle stimulating hormone, and also in estrogen,
      having oscillatory periods of 2-12 hours. There was also a longer-period (Q2-3
      days) emergent rhythm in progesterone. In the mid-luteal phase, estrogen and
      progesterone rhythms were correlated, and all hormones showed an approximately 6
      hour periodicity. CONCLUSIONS: To our knowledge, the oscillatory behavior of
      peripheral sex steroids in the follicular phase has not been previously noted.

PMID- 14702004
TI  - Does diabetes protect or provoke Alzheimer's disease? Insights into the
      pathobiology and future treatment of Alzheimer's disease.
AB  - Diabetes mellitus has long been considered a risk factor for the development of
      vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus
      significantly increases risk for the development of Alzheimer's disease,
      independent of vascular risk factors. As insulin's role as a neuromodulator in
      the brain has been described, its significance for AD has also emerged. Insulin
      dysregulation may contribute to AD pathology through several mechanisms including
      decreased cortical glucose utilization particularly in the hippocampus and
      entorhinal cortex; increased oxidative stress through the formation of advanced
      glycation end-products; increased Tau phosphorylation and neurofibrillary tangle
      formation; increased b-amyloid aggregation through inhibition of insulin
      degrading enzyme. Future treatment of AD might involve pharmacologic and dietary
      manipulations of insulin and glucose regulation.

PMID- 14702005
TI  - The role of cardiovascular risk factors in Alzheimer's disease.
AB  - The distinction between Alzheimer's disease and vascular dementia, the two most
      common types of dementia, has been undermined by recent advances in
      epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular
      risk factors, traditionally regarded as distinguishing criteria between the two
      entities, have been shown to be associated with both AD and vascular dementia. In
      this article, we propose mechanisms of action of cardiovascular risk factors in
      AD, suggest possible explanations for the overlap with vascular dementia and
      discuss the implications this might have on future differential diagnosis,
      research, and treatment strategies.

PMID- 14702006
TI  - Emerging therapeutics for Alzheimer's disease: an avenue of hope.
AB  - Emerging therapies for Alzheimer's disease offer hope to patients and their
      caregivers. Future treatments will probably include combination approaches with
      agents that modify amyloid processing, deposition, and clearance. One example,
      the AD vaccine, reduced amyloid burden and changed behavior in animal models of
      AD, but the human trial was halted when several subjects developed brain
      inflammation. Anti-inflammatory agents have epidemiologic support, but clinical
      trials have been disappointing, possibly related to inadequate study with anti
      inflammatory agents that modify amyloid processing. Agents that target known
      cardiovascular risk factors, such as hypercholesterolemia, hypertension, and
      insulin resistance, have epidemiologic, preclinical, and clinical evidence to
      warrant further investigation. Heavy metal chelators, antioxidants, neurotrophic
      factors, glutaminergic modulators, and agents that modify hyperphosphorylation of
      Tau are other approaches in research and development.

PMID- 14702007
TI  - Current concepts in the prevention of Alzheimer's disease.
AB  - Alzheimer's disease represents a significant challenge to the aging population.
      Since most estimates suggest that AD has a multifactorial etiology, the challenge
      to find preventative approaches is particularly great. With the aging of the
      population and the very high incidence from the eighth decade on, the challenge
      is further enhanced by the need to think of relatively safe interventions given
      the relative frailty of this elderly population. The need to find safe
      treatments, or ones with well-understood safety profiles, has led to the
      examination of known agents for potential dementia-preventing properties. Data
      supporting these interventions comes from observational studies, laboratory
      analyses, and clinical trials. Potential mechanisms for prevention of AD include
      anti-inflammatory and antioxidant approaches. Modulation of risk factors
      associated with cardiac disease may also reduce the risk of AD. Known agents have
      been examined for their potential to modify amyloid pathology. Trial designs to
      address prevention of AD include both primary and secondary prevention studies as
      well designs to assess slowing disease progression. Information can also be
      gathered when dementia evaluation is added to ongoing studies. As results from
      these studies becoming available, we will be able to refine our approach to
      managing this disease.

PMID- 14702011
TI  - FITS: New insights and lessons learned.

PMID- 14702012
TI  - Feeding infants and toddlers study: overview of the study design.
AB  - OBJECTIVE: Describe the design, data collection procedures, and sample
      characteristics of the Feeding Infants and Toddlers Study. DESIGN: We conducted
      up to three telephone interviews with a random sample of parents or caregivers of
      infants and toddlers four to 24 months of age from March to July 2002. The three
      interviews included (a) a recruitment and household interview; (b) a 24-hour
      dietary recall, with supplementary questions on growth, development, and feeding
      patterns; and (c) a second dietary recall for a random subset of the sample. Two
      age subgroups of infants (four to six months and nine to 11 months) were over
      sampled. Sample weights adjusted for over sampling, nonresponse, and under
      coverage of some subgroups in the sample frame. SUBJECTS: A national random
      sample of 3,022 infants and toddlers, with two days of dietary recall available
      for 703 sample members. RESULTS: Of sampled households that could be located and
      had an eligible child in the study age range, the response rate to the
      recruitment interview was 73%. Of recruited households, the response rate for the
      dietary recall interview was 94%. APPLICATIONS/CONCLUSIONS: The Feeding Infants
      and Toddlers Study (FITS) provides a wealth of data on the food and nutrient
      intakes, background characteristics, growth and development milestones, and
      feeding patterns and transitions for a nationally representative sample of
      infants and toddlers. Subsequent papers in this journal issue present study
      findings and conclusions from in-depth analysis of the FITS data.

PMID- 14702013
TI  - Nutrient intakes of infants and toddlers.
AB  - OBJECTIVES: To assess the nutrient adequacy of the diets of US infants and
      toddlers 4 to 24 months of age. DESIGN: Descriptive analysis of the usual
      nutrient intakes of infants and toddlers using 24-hour recall data from the 2002
      Feeding Infants and Toddlers Study. SUBJECTS: A national random sample of 3,022
      infants and toddlers, with 2 days of recall available for 703 sample members.
      Sample sizes by age were: infants 4 to 6 months (n=862), infants 7 to 11 months
      (n=1,162), and toddlers 12 to 24 months (n=998). STATISTICAL ANALYSES PERFORMED:
      Using the personal computer version of the Software for Intake Distribution
      Estimation, we estimated (where applicable) the percentage of infants and
      toddlers with usual intakes below the estimated average requirement, compared the
      means of usual nutrient intake distributions with adequate intake levels, and
      compared the 99th percentile of usual intake distributions with tolerable upper
      intake levels. RESULTS: For infants under 12 months of age, mean usual intakes
      exceeded the adequate intake for all nutrients. For toddlers 12 to 24 months of
      age, the estimated prevalence of inadequacy was low for most nutrients; however,
      58% of toddlers had usual vitamin E intakes less than the estimated average
      requirement. Mean energy intake exceeded the estimated energy requirement by 10%
      for infants 4 to 6 months, 23% for infants 7 to 12 months, and 31% for toddlers
      12 to 24 months of age. The discrepancy between mean energy intake and the
      estimated energy requirement for infants 4 to 6 months of age was larger for
      infants fed solids than for infants consuming only breast milk or formula. Fiber
      intakes of toddlers were below the adequate intake. APPLICATIONS: Studies should
      examine whether parents overreport foods consumed by infants and toddlers, and
      whether infants and toddlers are consuming more energy than required. Additional
      research is indicated to substantiate some of the new Dietary Reference Intakes
      for infants and children 1 to 3 years of age.

PMID- 14702014
TI  - Feeding infants and toddlers study: What foods are infants and toddlers eating?
AB  - OBJECTIVE: To describe the food consumption patterns of US infants and toddlers,
      4 to 24 months of age. DESIGN: Descriptive analysis of data collected in the 2002
      Feeding Infants and Toddlers study based on telephone interviews and 24-hour
      dietary recalls. SUBJECTS: A national random sample of 3,022 infants and toddlers
      age 4 to 24 months. STATISTICAL ANALYSES PERFORMED: The percentage of infants and
      toddlers consuming foods from specific food groups was estimated for six age
      groups, using a single 24-hour recall. RESULTS: Infants as young as 7 months of
      age showed food patterns that have been observed in older children and adults.
      From 18% to 33% of infants and toddlers between ages 7 and 24 months consumed no
      discrete servings of vegetables, and 23% to 33% consumed no fruits. French fries
      were one of the three most common vegetables consumed by infants 9 to 11 months
      of age. By 15 to 18 months, french fries were the most common vegetable. Almost
      half (46%) of 7- to 8-month-olds consumed some type of dessert, sweet, or
      sweetened beverage, and this percentage increased as age increased. By 19 to 24
      months, 62% of toddlers consumed a baked dessert, 20% consumed candy, and 44%
      consumed a sweetened beverage. APPLICATIONS: Parents and caregivers should be
      encouraged to offer a wide variety of vegetables and fruits daily, with emphasis
      on dark green, leafy, and deep yellow vegetables and colorful fruits. They should
      offer desserts, sweets, sweetened beverages, and salty snacks only occasionally,
      offering nutrient-dense, age-appropriate foods as alternatives (eg, fruit,
      cheese, yogurt, and cereals). Water, milk, and 100% fruit juices should be
      offered as alternative beverages. Because family food choices influence what
      foods are offered to children, family-based approaches to developing healthy
      eating habits may be helpful.

PMID- 14702015
TI  - Feeding infants and toddlers study: Improvements needed in meeting infant feeding
      recommendations.
AB  - OBJECTIVE: To assess adherence to infant feeding recommendations among a sample
      of infants and toddlers four to 24 months of age in the United States. DESIGN:
      Descriptive analysis of data collected in the 2002 Feeding Infants and Toddlers
      Study (FITS) based on telephone interviews and 24-hour dietary recalls collected
      with the Nutrition Data System for Research of the University of Minnesota.
      SUBJECTS: A national random sample of 3,022 infants and toddlers age four to 24
      months, including 2,024 infants age four to 11 months. MAIN OUTCOME MEASURES:
      Breastfeeding, timing of introduction of complementary foods, and adherence to
      infant feeding recommendations. STATISTICAL ANALYSES: Means and standard errors,
      percentile distributions, and percentages by age group (four to six months, seven
      to eight months, and nine to 11 months). RESULTS: About 76% of infants and
      toddlers were fully or partly breastfed at birth. This percentage declined to 30%
      at six months and 16% at 12 months-short of Healthy People 2010 goals of 50% and
      25%, respectively. The average duration of breastfeeding was 5.5 months for all
      who initiated breastfeeding. About two-thirds of infants had been introduced to
      complementary foods between four and six months-the period recommended by the
      American Academy of Pediatrics (AAP); 17% consumed juice before the AAP
      recommended age of six months or later. Twenty-two percent of infants nine to 11
      months consumed cow's milk on a daily basis before the recommended age of 12
      months or later, and one in 10 consumed french fries and/or sweetened beverages
      on any given day. APPLICATIONS/CONCLUSIONS: More parents and caregivers can
      benefit from guidance about the introduction of developmentally appropriate,
      micronutrient-rich first solid foods such as iron-rich infant cereals, iron
      fortified grain products, meats, soft fruits, and cooked vegetables and the
      importance of breastfeeding through the first year of life. A smaller proportion
      of parents and caregivers require guidance on delaying the introduction of juices
      until six months of age and cow's milk other than formula until one year of age.

PMID- 14702016
TI  - Toddlers' transition to table foods: Impact on nutrient intakes and food
      patterns.
AB  - OBJECTIVE: To describe the differential changes in average intakes of nutrients
      and food groups among higher versus lower table food consumers during the
      transition from baby foods to table foods. DESIGN: A comparative analysis of food
      and nutrient intakes in the lowest versus highest quartile of energy from table
      foods based on 24-hour dietary recall data. SUBJECTS: A national random sample of
      1,677 US infants and toddlers 9 to 24 months in the 2002 Feeding Infants and
      Toddlers Study (FITS). STATISTICAL ANALYSES: Mean and percentiles of energy
      intake from table foods; comparisons of mean daily nutrient intake and the
      percentages consuming various foods and beverages in the lowest versus highest
      quartile of energy from table foods, by age. RESULTS: The mean percentage of
      energy from table foods increased from 25% at 9 to 11 months to 63% at 19 to 24
      months. Mean intakes of energy, macronutrients, sodium, folate, and fiber were
      significantly higher for children 9 to 11, 12 to 14, and 15 to 18 months in the
      highest table food energy quartiles compared to the lowest. Mean calcium intakes
      were significantly lower among toddlers 15 to 24 months consuming high table food
      energy, and associated with lower milk consumption. A higher percentage of
      children in the lowest quartiles of energy from table food were consuming deep
      yellow vegetables among ages 9 through 14 months. The percentage of children
      consuming popular items such as pizza, carbonated sodas, French fries, candy and
      other sweets was higher among those who consumed more energy from table foods in
      every age group. APPLICATIONS: The epidemic of overweight children mandates
      helping parents teach healthy eating habits early. Messages that educate parents
      and caregivers about toddler feeding include: (1) offer a wide variety of
      nutritious foods, particularly fruits and vegetables, in forms that are
      developmentally appropriate, (2) continue to feed foods that are good sources of
      iron, such as iron-fortified infant cereals, ready-to-eat cereals that are high
      in iron, and meats, (3) to ensure adequate calcium intake, build the habit of
      drinking milk, and (4) teach children to recognize and honor their hunger and
      satiety cues.

PMID- 14702017
TI  - Transitions in infants' and toddlers' beverage patterns.
AB  - OBJECTIVE: To describe transitions and patterns in infants' and toddlers'
      beverage intakes, with focus on nonmilk beverages. DESIGN: A cross-sectional
      study was conducted by telephone to obtain a 24-hour dietary recall of infants'
      and toddlers' food intakes, as reported by mothers or other primary caregivers.
      SUBJECTS: A nationwide sample of infants and toddlers (n=3,022) ages 4 to 24
      months, who participated in the Feeding Infants and Toddlers Study (FITS).
      ANALYSES: Beverages were categorized as total milks (ie, breast milk, infant
      formulas, cow's milk, soy milk, goat's milk), 100% juices, fruit drinks,
      carbonated beverages, water, and "other." Analyses included means +/- standard
      deviations, percentages, frequencies, nutrient densities, and linear regression.
      RESULTS: Beverages provided 84% of total daily food energy for infants 4 to 6
      months of age, decreasing to 36% at ages 19 to 24 months. Apple juice and apple
      flavored fruit drinks were the most frequently consumed beverages in the 100%
      juice and fruit drink categories, respectively. Juices, fruit drinks, and
      carbonated beverages appeared to displace milk in toddlers' diets (P<.0001).
      APPLICATIONS/CONCLUSIONS: This research shows that beverages make important
      contributions to infants' and toddlers' energy and nutrient needs, but they must
      be wisely chosen. Registered dietitians should advise parents and caregivers that
      excessive intakes of any beverage, including milks and 100% juices, may displace
      other foods and beverages in the diet and/or contribute to excess food energy
      (kcal). Further research is needed to define excessive amounts in each beverage
      category, and such guidance could be very useful to parents and caregivers of
      infants and toddlers.

PMID- 14702018
TI  - Developmental milestones and self-feeding behaviors in infants and toddlers.
AB  - OBJECTIVES: To identify ages at which gross motor developmental milestones and
      fine motor skills required for self-feeding were reported by primary caregivers
      and to relate these self-feeding skills to energy and nutrient intakes. DESIGN:
      Cross-sectional survey of households with infants/toddlers, ages 4 to 24 months.
      SUBJECTS/SETTING: Telephone survey using a national random sample of infants and
      toddlers (n=3,022). METHODS: Primary caregivers reported their children's food
      intake (one 24-hour recall), the ages when caregivers reported self-feeding
      skills were shown, and the number of teeth. STATISTICAL ANALYSES PERFORMED:
      Children's reported ages for gross motor developmental milestones, self-feeding
      skills, and the number of erupted teeth were summarized. Using t tests,
      differences in energy and nutrient intake were determined by age groupings and by
      the absence or presence of each self-feeding skill. RESULTS: Self-feeding skills
      achieved in the first 2 years and details about age ranges at which developmental
      readiness to self-feed were evidenced are described. The ages at which children
      were reported to show gross motor developmental milestones and eruption of teeth
      occurred within expected age ranges. A majority of the children who were reported
      to show developmental readiness to self-feed at an earlier age (7 to 14 months)
      had higher intakes of energy and most nutrients than those who did not. By 15 to
      18 months, most of the children were reported to show comparable self-feeding
      skills regardless of whether they self-fed earlier or later.
      APPLICATIONS/CONCLUSIONS: Assuming a variety of nutritious foods are offered to
      infants and toddlers, caregivers may encourage self-feeding without concern for
      jeopardizing energy and nutrient adequacy. In the first year, the addition of
      foods that require chewing should reflect the number of erupted teeth.

PMID- 14702019
TI  - Prevalence of picky eaters among infants and toddlers and their caregivers'
      decisions about offering a new food.
AB  - OBJECTIVES: To determine the prevalence of infants and toddlers who were
      considered picky eaters, the predictors of picky eater status and its association
      with energy and nutrient intakes, food group use, and the number of times that
      caregivers offered a new food before deciding their child disliked it. DESIGN:
      Cross-sectional survey of households with infants and toddlers (ages four to 24
      months) was conducted. SUBJECTS/SETTING: National random sample of 3,022 infants
      and toddlers. METHODS: Data included caregiver's socioeconomic and demographic
      information, infants' and toddlers' food intake (24-hour recall), ethnicity, and
      caregivers' reports of specified times that new foods were offered before
      deciding the child disliked it. STATISTICAL ANALYSES: For picky and nonpicky
      eaters, t tests were used to determine significant mean differences in energy and
      nutrient intakes. Logistic regression was used to predict picky eater status, and
      chi(2) tests were used for differences in the specified number of times that new
      foods were offered. RESULTS: The percentage of children identified as picky
      eaters by their caregivers increased from 19% to 50% from four to 24 months.
      Picky eaters were reported at all ages for both sexes, all ethnicities, and all
      ranges of household incomes. On a day, both picky and nonpicky eaters met or
      exceeded current age-appropriate energy and dietary recommendations. Older
      children were more likely to be picky. Those in the higher weight-for-age
      percentiles were less likely to be picky. The highest number of times that
      caregivers offered a new food before deciding the child disliked it was three to
      five. APPLICATIONS/CONCLUSIONS: Dietetics professionals need to be aware that
      caregivers who perceive their child as a picky eater are evident across gender,
      ethnicity, and household incomes. When offering a new food, mothers need to
      provide many more repeated exposures (eg, eight to 15 times) to enhance
      acceptance of that food than they currently do.

PMID- 14702020
TI  - Meal and snack patterns of infants and toddlers.
AB  - OBJECTIVE: To describe meal and snack patterns of infants and toddlers. DESIGN: A
      cross-sectional telephone survey in which mothers reported their infants' and
      toddlers' food and beverage intakes for a 24-hour period. SUBJECTS: Subjects
      included 3,022 infants and toddlers, ages 4 to 24 months, in the Feeding Infants
      and Toddlers Study. STATISTICAL ANALYSES PERFORMED: Means+/-standard deviations,
      frequencies, percentages, energy and nutrient analyses, nutrient densities.
      RESULTS: On average, infants and toddlers were fed seven times per day. The
      breakfast, lunch, and dinner pattern, plus snacks, emerged at 7 to 8 months and
      was well established by 9 to 11 months. Breakfasts were higher in nutrient
      density for iron, folate, and calcium than other meals. The percentage of
      children reported to be eating snacks increased with age. The afternoon snack was
      consumed by over 80% of toddlers (12 to 24 months), and snacks provided about 25%
      of toddlers' daily energy intakes. Typical snack foods for toddlers were milk,
      water, cookies, crackers, chips, and fruit drinks. APPLICATIONS/CONCLUSIONS:
      Results of this study provide parents and professionals with specific information
      about meal and snack patterns, thereby allowing development of targeted messages
      and/or strategies to improve the dietary patterns of infants and toddlers.
      Although most foods provided to the Feeding Infants and Toddlers Study infants
      and toddlers were nutritionally and developmentally appropriate, snack choices
      could be improved by delaying introduction of and limiting exposures to foods low
      in nutrients and high in calories.

PMID- 14702021
TI  - Nutrient intakes and food choices of infants and toddlers participating in WIC.
AB  - OBJECTIVES: To examine the nutrient intakes, foods consumed, and feeding patterns
      of infants and toddlers participating in the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC). DESIGN: Cross-sectional telephone
      survey, including 24-hour dietary recalls of infants' and toddlers' food and
      nutrient intakes, as reported by parents or other primary caregivers. SUBJECTS:
      National random sample of 3,022 children ages 4 to 24 months who participated in
      the 2002 Feeding Infants and Toddlers study. Sample sizes by age were infants 4
      to 6 months: 265 WIC participants, 597 nonparticipants; infants 7 to 11 months:
      351 WIC participants, 808 nonparticipants; and toddlers 12 to 24 months: 205 WIC
      participants, 791 nonparticipants. STATISTICAL ANALYSES PERFORMED: We used
      Statistical Analysis Software (version 8.2) to examine the breastfeeding status,
      infant feeding patterns, and foods consumed; the personal computer version of the
      Software for Intake Distribution Estimation to estimate mean usual intake of food
      energy and of key nutrients targeted by the WIC program; and methods recommended
      by the Institute of Medicine to assess nutrient adequacy. RESULTS: Infants
      participating in WIC were less likely than nonparticipants to have ever been
      breastfed or to be currently breastfeeding, and they were more likely to be
      consuming formula. Mean usual nutrient intakes exceeded the adequate intake for
      WIC participants, and the percentage with inadequate nutrient intake was less
      than 1%. Reported mean energy intakes exceeded mean energy requirements, with the
      largest discrepancy observed for WIC participants. Sizeable proportions of WIC
      and non-WIC infants and toddlers did not consume fruits and vegetables on the
      recall day. APPLICATIONS: WIC providers should focus nutrition education on
      appropriate infant and toddler feeding patterns, should continue to reinforce
      their message of the importance delaying the use of cow's milk until 1 year of
      age, and should stress the importance of fruit and vegetable consumption.

PMID- 14702022
TI  - Simulated apoptosis/neurogenesis regulates learning and memory capabilities of
      adaptive neural networks.
AB  - Characterization of neuronal death and neurogenesis in the adult brain of birds,
      humans, and other mammals raises the possibility that neuronal turnover
      represents a special form of neuroplasticity associated with stress responses,
      cognition, and the pathophysiology and treatment of psychiatric disorders.
      Multilayer neural network models capable of learning alphabetic character
      representations via incremental synaptic connection strength changes were used to
      assess additional learning and memory effects incurred by simulation of
      coordinated apoptotic and neurogenic events in the middle layer. Using a
      consistent incremental learning capability across all neurons and experimental
      conditions, increasing the number of middle layer neurons undergoing turnover
      increased network learning capacity for new information, and increased forgetting
      of old information. Simulations also showed that specific patterns of neural
      turnover based on individual neuronal connection characteristics, or the temporal
      spatial pattern of neurons chosen for turnover during new learning impacts new
      learning performance. These simulations predict that apoptotic and neurogenic
      events could act together to produce specific learning and memory effects beyond
      those provided by ongoing mechanisms of connection plasticity in neuronal
      populations. Regulation of rates as well as patterns of neuronal turnover may
      serve an important function in tuning the informatic properties of plastic
      networks according to novel informational demands. Analogous regulation in the
      hippocampus may provide for adaptive cognitive and emotional responses to novel
      and stressful contexts, or operate suboptimally as a basis for psychiatric
      disorders. The implications of these elementary simulations for future biological
      and neural modeling research on apoptosis and neurogenesis are discussed.

PMID- 14702023
TI  - Olanzapine penetration into brain is greater in transgenic Abcb1a P-glycoprotein
      deficient mice than FVB1 (wild-type) animals.
AB  - The transmembrane energy-dependent efflux transporter P-glycoprotein (P-gp)
      limits a range of drugs from penetrating cells and deposits them into the
      extracellular space. P-gp is highly expressed in several normal tissues,
      including the luminal surface of capillary endothelial cells in the brain of
      humans. In this study, we tested whether olanzapine distribution to tissues
      highly expressing P-gp or devoid of this transporter was similar in Abcb1a (-/-)
      mice lacking P-gp and control animals. At 1 h following the intraperitoneal
      injection of 2.5 microg olanzapine/g mouse, olanzapine concentrations were
      statistically and significantly higher in brain (three-fold), liver (2.6-fold),
      and kidney (1.8-fold) of Abcb1a (-/-) mice than those of the control FVB Abcb1a
      (+/+) mice, and not statistically different in plasma, spleen, or penile tissue.
      Similar differences were also found for the ratios of organ:plasma and
      organ:spleen between the two groups. This is the first report that the presence
      of the Abcb1a gene is an important factor controlling brain access to olanzapine.
      The finding that the brain penetration of olanzapine is limited by P-gp implies
      that the highly prevalent functional polymorphisms of ABCB1 in humans may be a
      factor contributing to variability in dose requirements for this antipsychotic
      drug.

PMID- 14702024
TI  - Independent evaluator knowledge of treatment in a multicenter comparative
      treatment study of panic disorder.
AB  - The purpose of this study was to examine independent evaluators' (IEs) blindness
      to treatment condition during a Multicenter Comparative Treatment Study of Panic
      Disorder. IEs were 15 doctoral- and masters-level clinicians in psychology,
      social work, and medicine. They conducted three post-treatment assessments with
      each patient. Immediately after each assessment interview, IEs completed a form
      indicating which of the five possible treatments they believed the patient had
      received and any specific information that provided IEs with information about a
      patient's treatment condition. These forms were completed for 170 patients.
      Analyses were conducted to determine the accuracy of guesses about treatment
      condition by IEs during post-treatment assessments, the relationship between
      accuracy of IE guessing and actual treatment assignment, the relationship between
      accurate guessing and outcome ratings, and contributors to the breaking of the
      blind. A significant relationship was found between IE guesses and actual
      treatment at all three assessment points, across individual IEs, treatment sites,
      and IE professional affiliations. IEs were no more accurate in their guessing
      about patients taking medication than those receiving behavior therapy. Patients
      and project staff inadvertently provided information to IEs that enhanced the
      rates of accurate guessing. Implications of these findings on interpretation of
      the treatment study are discussed, and recommendations are made for improving
      blindness procedures.

PMID- 14702025
TI  - Cerebrospinal fluid corticotropin-releasing factor and perceived early-life
      stress in depressed patients and healthy control subjects.
AB  - Previous studies have reported elevated concentrations of cerebrospinal fluid
      (CSF) corticotropin-releasing factor (CRF) in patients with major depression.
      Elevations of CSF CRF have also been reported in adult laboratory animals exposed
      to the stress of brief maternal deprivation or maternal neglect in the neonatal
      or preweaning period. The present study was designed to determine whether major
      depression and a history of perceived early adversity in childhood are
      independently associated with elevated CSF CRF concentrations in adults. In this
      case-control study, 27 medication-free adults with major depression and 25
      matched controls underwent standardized lumbar puncture for collection of a
      single CSF sample at 1200. Subjects provided data about significant adverse early
      life experiences and rated their global perceived level of stress during pre
      school and preteen years on a six-point Likert scale. The mean difference in CSF
      CRF between depressed patients and controls did not reach statistical
      significance. In a regression model, perceived early-life stress was a
      significant predictor of CSF CRF, but depression was not. Perinatal adversity and
      perceived adversity in the preteen adversity years (ages 6-13 years) were both
      independently associated with decreasing CSF CRF concentrations. The relationship
      observed between perceived early-life stress and adult CSF CRF concentrations in
      this study closely parallels recent preclinical findings. More work is needed to
      elucidate the critical nature and timing of early events that may be associated
      with enduring neuroendocrine changes in humans.

PMID- 14702026
TI  - Chance is a necessity.

PMID- 14702027
TI  - A call for accurate phenotype definition in the study of complex disorders.

PMID- 14702030
TI  - Conquering the complexity of p53.

PMID- 14702031
TI  - White meat or dark?

PMID- 14702032
TI  - Two Pax are better than one.

PMID- 14702033
TI  - Marking Xs, together and separately.

PMID- 14702034
TI  - Diverse powerhouses.

PMID- 14702037
TI  - The four Rs of RNA-directed evolution.
AB  - The way we quantify the human genome has changed markedly. The estimated
      percentage of the genome derived from retrotransposition has increased (now 45%;
      refs. 1,2), as have the estimates for alternative splicing (now 41-60% of
      multiexon genes), antisense transcription (now 10-20% of genes) and non-protein
      coding RNA (now approximately 7% of full-length cDNAs). Concomitantly, the
      estimated number of protein-coding genes (now approximately 24,500) has
      decreased. These numbers support an RNA-centric view of evolution in which
      phenotypic diversity arises through extensive RNA processing and widespread RNA
      directed rewriting of DNA enables dissemination of 'selfish' RNAs associated with
      successful outcomes. The numbers also indicate important roles for sense
      antisense transcription units (SATs) and coregulatory RNAs (coRNAs) in directing
      the read-out of genetic information, in reconciling different regulatory inputs
      and in transmitting epigenetic information to progeny. Together, the actions of
      reading, 'riting, 'rithmetic and replication constitute the four Rs of RNA
      directed evolution.

PMID- 14702038
TI  - Growth and specification of the eye are controlled independently by Eyegone and
      Eyeless in Drosophila melanogaster.
AB  - Control of growth determines the size and shape of organs. Localized signals
      known as 'organizers' and members of the Pax family of proto-oncogenes are both
      elements in this control. Pax proteins have a conserved DNA-binding paired
      domain, which is presumed to be essential for their oncogenic activity. We
      present evidence that the organizing signal Notch does not promote growth in eyes
      of D. melanogaster through either Eyeless (Ey) or Twin of eyeless (Toy), the two
      Pax6 transcription factors. Instead, it acts through Eyegone (Eyg), which has a
      truncated paired domain, consisting of only the C-terminal subregion. In humans
      and mice, the sole PAX6 gene produces the isoform PAX6(5a) by alternative
      splicing; like Eyegone, this isoform binds DNA though the C terminus of the
      paired domain. Overexpression of human PAX6(5a) induces strong overgrowth in
      vivo, whereas the canonical PAX6 variant hardly effects growth. These results
      show that growth and eye specification are subject to independent control and
      explain hyperplasia in a new way.

PMID- 14702040
TI  - RPA regulates telomerase action by providing Est1p access to chromosome ends.
AB  - Replication protein A (RPA) is a highly conserved single-stranded DNA-binding
      protein involved in DNA replication, recombination and repair. We show here that
      RPA is present at the telomeres of the budding yeast Saccharomyces cerevisiae,
      with a maximal association in S phase. A truncation of the N-terminal region of
      Rfa2p (associated with the rfa2Delta40 mutated allele) results in severe telomere
      shortening caused by a defect in the in vivo regulation of telomerase activity.
      Cells carrying rfa2Delta40 show impaired binding of the protein Est1p, which is
      required for telomerase action. In addition, normal telomere length can be
      restored by expressing a Cdc13-Est1p hybrid protein. These findings indicate that
      RPA activates telomerase by loading Est1p onto telomeres during S phase. We
      propose a model of in vivo telomerase action that involves synergistic action of
      RPA and Cdc13p at the G-rich 3' overhang of telomeric DNA.

PMID- 14702039
TI  - Complete sequencing and characterization of 21,243 full-length human cDNAs.
AB  - As a base for human transcriptome and functional genomics, we created the "full
      length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the
      entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897
      clusters) were unique to the FLJ collection. About half of them (5,416) seemed to
      be protein-coding. Of those, 1,999 clusters had not been predicted by
      computational methods. The distribution of GC content of nonpredicted cDNAs had a
      peak at approximately 58% compared with a peak at approximately 42%for predicted
      cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in
      current gene prediction procedures. The rest of the cDNAs unique to the FLJ
      collection (5,481) contained no obvious open reading frames (ORFs) and thus are
      candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern
      of splicing. The distribution of GC content of noncoding cDNAs was narrow and had
      a peak at approximately 42%, relatively low compared with that of protein-coding
      cDNAs.

PMID- 14702041
TI  - Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and
      inhibition of p53.
AB  - Aurora kinase A (also called STK15 and BTAK) is overexpressed in many human
      cancers. Ectopic overexpression of aurora kinase A in mammalian cells induces
      centrosome amplification, chromosome instability and oncogenic transformation, a
      phenotype characteristic of loss-of-function mutations of p53. Here we show that
      aurora kinase A phosphorylates p53 at Ser315, leading to its ubiquitination by
      Mdm2 and proteolysis. p53 is not degraded in the presence of inactive aurora
      kinase A or ubiquitination-defective Mdm2. Destabilization of p53 by aurora
      kinase A is abrogated in the presence of mutant Mdm2 that is unable to bind p53
      and after repression of Mdm2 by RNA interference. Silencing of aurora kinase A
      results in less phosphorylation of p53 at Ser315, greater stability of p53 and
      cell-cycle arrest at G2-M. Cells depleted of aurora kinase A are more sensitive
      to cisplatin-induced apoptosis, and elevated expression of aurora kinase A
      abolishes this response. In a sample of bladder tumors with wild-type p53,
      elevated expression of aurora kinase A was correlated with low p53 concentration.
      We conclude that aurora kinase A is a key regulatory component of the p53 pathway
      and that overexpression of aurora kinase A leads to increased degradation of p53,
      causing downregulation of checkpoint-response pathways and facilitating oncogenic
      transformation of cells.

PMID- 14702042
TI  - Chromosome stability, in the absence of apoptosis, is critical for suppression of
      tumorigenesis in Trp53 mutant mice.
AB  - The p53 protein integrates multiple upstream signals and functions as a tumor
      suppressor by activating distinct downstream genes. At the cellular level, p53
      induces apoptosis, cell cycle arrest and senescence. A rare mutant form of p53
      with the amino acid substitution R175P, found in human tumors, is completely
      defective in initiating apoptosis but still induces cell cycle arrest. To
      decipher the functional importance of these pathways in spontaneous
      tumorigenesis, we used homologous recombination to generate mice with mutant p53
      R172P (the mouse equivalent of R175P in humans). Mice inheriting two copies of
      this mutation (Trp53(515C/515C)) escape the early onset of thymic lymphomas that
      characterize Trp53-null mice. At 7 months of age, 90% of Trp53-null mice had
      died, but 85% of Trp53(515C/515C) mice were alive and tumor-free, indicating that
      p53-dependent apoptosis was not required for suppression of early onset of
      spontaneous tumors. The lymphomas and sarcomas that eventually developed in
      Trp53(515C/515C) mice retained a diploid chromosome number, in sharp contrast to
      aneuploidy observed in tumors and cells from Trp53-null mice. The ability of
      mutant p53-R172P to induce a partial cell cycle arrest and retain chromosome
      stability are crucial for suppression of early onset tumorigenesis.

PMID- 14702043
TI  - Conversion of biliary system to pancreatic tissue in Hes1-deficient mice.
AB  - The biliary system, pancreas and liver all develop from the nearby foregut at
      almost the same time in mammals. The molecular mechanisms that determine the
      identity of each organ in this complex area are unknown. Hes1 encodes the basic
      helix-loop-helix protein Hes1 (ref. 1), which represses positive basic helix-loop
      helix genes such as Neurog3 (ref. 3). Expression of Hes1 is controlled by the
      evolutionarily conserved Notch pathway. Hes1 operates as a general negative
      regulator of endodermal endocrine differentiation, and defects in Notch signaling
      lead to accelerated pancreatic endocrine differentiation. Mutations in JAG1,
      encoding a Notch ligand, cause the Alagille syndrome in humans, characterized by
      poor development of the biliary system, suggesting that the Notch pathway is also
      involved in normal biliary development. Here we show that Hes1 is expressed in
      the extrahepatic biliary epithelium throughout development and that Hes1
      deficient mice have gallbladder agenesis and severe hypoplasia of extrahepatic
      bile ducts. Biliary epithelium in Hes1-/- mice ectopically expresses the
      proendocrine gene Neurog3 (refs. 12,13), differentiates into endocrine and
      exocrine cells and forms acini and islet-like structures in the mutant bile
      ducts. Thus, biliary epithelium has the potential for pancreatic differentiation
      and Hes1 determines biliary organogenesis by preventing the pancreatic
      differentiation program, probably by directly repressing transcription of
      Neurog3.

PMID- 14702044
TI  - The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle
      fiber identity in response to Hedgehog signaling.
AB  - Vertebrate skeletal muscles comprise distinct fiber types that differ in their
      morphology, contractile function, mitochondrial content and metabolic properties.
      Recent studies identified the transcriptional coactivator PGC-1alpha as a key
      mediator of the physiological stimuli that modulate fiber-type plasticity in
      postembryonic development. Although myoblasts become fated to differentiate into
      distinct kinds of fibers early in development, the identities of regulatory
      proteins that determine embryonic fiber-type specification are still obscure.
      Here we show that the gene u-boot (ubo), a mutation in which disrupts the
      induction of embryonic slow-twitch fibers, encodes the zebrafish homolog of Blimp
      1, a SET domain-containing transcription factor that promotes the terminal
      differentiation of B lymphocytes in mammals. Expression of ubo is induced by
      Hedgehog (Hh) signaling in prospective slow muscle precursors, and its activity
      alone is sufficient to direct slow-twitch fiber-specific development by naive
      myoblasts. Our data provide the first molecular insight into the mechanism by
      which a specific group of muscle precursors is driven along a distinct pathway of
      fiber-type differentiation in response to positional cues in the vertebrate
      embryo.

PMID- 14702045
TI  - Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and
      Suv39h2 histone methyltransferases.
AB  - Telomeres are capping structures at the ends of eukaryotic chromosomes composed
      of TTAGGG repeats bound to an array of specialized proteins. Telomeres are
      heterochromatic regions. Yeast and flies with defects in activities that modify
      the state of chromatin also have abnormal telomere function, but the putative
      role of chromatin-modifying activities in regulating telomeres in mammals is
      unknown. Here we report on telomere length and function in mice null with respect
      to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called
      SUV39DN mice). Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3
      Lys9) in heterochromatic regions. We show that primary cells derived from SUV39DN
      mice have abnormally long telomeres relative to wild-type controls. Using
      chromatin immunoprecipitation (ChIP) analysis, we found that telomeres were
      enriched in di- and trimethylated H3-Lys9 but that telomeres of SUV39DN cells had
      less dimethylated and trimethylated H3-Lys9 but more monomethylated H3-Lys9.
      Concomitant with the decrease in H3-Lys9 methylation, telomeres in SUV39DN cells
      had reduced binding of the chromobox proteins Cbx1, Cbx3 and Cbx5, homologs of
      Drosophila melanogaster heterochromatin protein 1 (HP1). These findings indicate
      substantial changes in the state of telomeric heterochromatin in SUV39DN cells,
      which are associated with abnormal telomere elongation. Taken together, the
      results indicate epigenetic regulation of telomere length in mammals by Suv39h1
      and Suv39h2.

PMID- 14702049
TI  - Complacency about misconduct.

PMID- 14702046
TI  - Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans.
AB  - The genetic imprinting of individual loci or whole chromosomes, as in imprinted X
      chromosome inactivation in mammals, is established and reset during
      gametogenesis; defects in this process in the parent can result in disease in the
      offspring. We describe a sperm-specific chromatin-based imprinting of the X
      chromosome in the nematode Caenorhabditis elegans that is restricted to histone
      H3 modifications. The epigenetic imprint is established during spermatogenesis
      and its stability in the offspring is affected by the presence of a pairing
      partner during meiosis in the parental germ line. We observed that DNA lacking a
      pairing partner during meiosis, the normal situation for the X chromosome in
      males, is targeted for methylation of histone H3 at Lys9 (H3-Lys9) and can be
      silenced. Targeting unpaired DNA for silencing during meiosis, a potential
      hallmark of genome defense, could therefore have a conserved role in imprinted X
      chromosome inactivation and, ultimately, in sex chromosome evolution.

PMID- 14702050
TI  - Nature's twentieth-century highs.

PMID- 14702051
TI  - Plagiarism in Cambridge physics lab prompts calls for guidelines.

PMID- 14702052
TI  - Primate lab faces closure threat over mistreatment charge.

PMID- 14702054
TI  - Mars satellite flies into hunt for lost Beagle 2.

PMID- 14702053
TI  - Ecologists hit out at plan to export Argentinian parrots.

PMID- 14702055
TI  - Beef blockade greets first mad cow in United States.

PMID- 14702057
TI  - Music and chemistry: organ failure.

PMID- 14702058
TI  - Oceanography: all wired up.

PMID- 14702059
TI  - Joint efforts needed to forecast space weather.

PMID- 14702060
TI  - White House cost-cutting undermines productivity.

PMID- 14702061
TI  - Tough lessons for survival in hard academic times.

PMID- 14702066
TI  - Astrobiology: water, water, everywhere?

PMID- 14702067
TI  - Vision: the need for speed.

PMID- 14702068
TI  - Semiconductor physics: relativity on a chip.

PMID- 14702069
TI  - Palaeontology: Chinese lantern for early primates.

PMID- 14702071
TI  - Oceanography: the southern supplier.

PMID- 14702072
TI  - Cell biology: shape-shifting protein channel.

PMID- 14702073
TI  - Atmospheric pollution: the veil of two cities.

PMID- 14702075
TI  - Secrets of successful stone-skipping.
AB  - Skipping stones across water has been a popular pastime for thousands of years -
      the rules of the game have remained unchanged since the time of the ancient
      Greeks - and the world record, set by J. Coleman-McGhee in 1992, is believed to
      be 38 rebounds. Following earlier attempts to analyse the physics of this
      ancestral human activity, we focus here on the crucial moment in stone skipping:
      when the stone bounces on the water's surface. By monitoring the collision of a
      spinning disc with water, we have discovered that an angle of about 20 degrees
      between the stone and the water's surface is optimal with respect to the throwing
      conditions and yields the maximum possible number of bounces.

PMID- 14702076
TI  - Plant degradation: a nematode expansin acting on plants.
AB  - Expansin proteins, which have so far been identified only in plants, rapidly
      induce extension of plant cell walls by weakening the non-covalent interactions
      that help to maintain their integrity. Here we show that an animal, the plant
      parasitic roundworm Globodera rostochiensis, can also produce a functional
      expansin, which it uses to loosen cell walls when invading its host plant. As
      this nematode is known to be able to disrupt covalent bonds in plant cell walls,
      its accompanying ability to loosen non-covalent bonds challenges the prevailing
      view that animals are genetically poorly equipped to degrade plant cell walls.

PMID- 14702077
TI  - Reconstructing galaxy histories from globular clusters.
AB  - Nearly a century after the true nature of galaxies as distant 'island universes'
      was established, their origin and evolution remain great unsolved problems of
      modern astrophysics. One of the most promising ways to investigate galaxy
      formation is to study the ubiquitous globular star clusters that surround most
      galaxies. Globular clusters are compact groups of up to a few million stars. They
      generally formed early in the history of the Universe, but have survived the
      interactions and mergers that alter substantially their parent galaxies. Recent
      advances in our understanding of the globular cluster systems of the Milky Way
      and other galaxies point to a complex picture of galaxy genesis driven by
      cannibalism, collisions, bursts of star formation and other tumultuous events.

PMID- 14702078
TI  - A correlation between the cosmic microwave background and large-scale structure
      in the Universe.
AB  - Observations of distant supernovae and the fluctuations in the cosmic microwave
      background (CMB) indicate that the expansion of the Universe may be accelerating
      under the action of a 'cosmological constant' or some other form of 'dark
      energy'. This dark energy now appears to dominate the Universe and not only
      alters its expansion rate, but also affects the evolution of fluctuations in the
      density of matter, slowing down the gravitational collapse of material (into, for
      example, clusters of galaxies) in recent times. Additional fluctuations in the
      temperature of CMB photons are induced as they pass through large-scale
      structures and these fluctuations are necessarily correlated with the
      distribution of relatively nearby matter. Here we report the detection of
      correlations between recent CMB data and two probes of large-scale structure: the
      X-ray background and the distribution of radio galaxies. These correlations are
      consistent with those predicted by dark energy, indicating that we are seeing the
      imprint of dark energy on the growth of structure in the Universe.

PMID- 14702079
TI  - A large population of 'Lyman-break' galaxies in a protocluster at redshift z
      approximately 4.1.
AB  - The most massive galaxies and the richest clusters are believed to have emerged
      from regions with the largest enhancements of mass density relative to the
      surrounding space. Distant radio galaxies may pinpoint the locations of the
      ancestors of rich clusters, because they are massive systems associated with
      'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen.
      A powerful technique for detecting high-redshift galaxies is to search for the
      characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just
      shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by
      the intervening intergalactic medium. Here we report multicolour imaging of the
      most distant candidate protocluster, TN J1338-1942 at a redshift z approximately
      4.1. We find a large number of objects with the characteristic colours of
      galaxies at that redshift, and we show that this excess is concentrated around
      the targeted dominant radio galaxy. Our data therefore indicate that TN J1338
      1942 is indeed the most distant cluster progenitor of a rich local cluster, and
      that galaxy clusters began forming when the Universe was only ten per cent of its
      present age.

PMID- 14702080
TI  - Coherent spin manipulation without magnetic fields in strained semiconductors.
AB  - A consequence of relativity is that in the presence of an electric field, the
      spin and momentum states of an electron can be coupled; this is known as spin
      orbit coupling. Such an interaction opens a pathway to the manipulation of
      electron spins within non-magnetic semiconductors, in the absence of applied
      magnetic fields. This interaction has implications for spin-based quantum
      information processing and spintronics, forming the basis of various device
      proposals. For example, the concept of spin field-effect transistors is based on
      spin precession due to the spin-orbit coupling. Most studies, however, focus on
      non-spin-selective electrical measurements in quantum structures. Here we report
      the direct measurement of coherent electron spin precession in zero magnetic
      field as the electrons drift in response to an applied electric field. We use
      ultrafast optical techniques to spatiotemporally resolve spin dynamics in
      strained gallium arsenide and indium gallium arsenide epitaxial layers.
      Unexpectedly, we observe spin splitting in these simple structures arising from
      strain in the semiconductor films. The observed effect provides a flexible
      approach for enabling electrical control over electron spins using strain
      engineering. Moreover, we exploit this strain-induced field to electrically drive
      spin resonance with Rabi frequencies of up to approximately 30 MHz.

PMID- 14702081
TI  - The interface between silicon and a high-k oxide.
AB  - The ability of the semiconductor industry to continue scaling microelectronic
      devices to ever smaller dimensions (a trend known as Moore's Law) is limited by
      quantum mechanical effects: as the thickness of conventional silicon dioxide
      (SiO(2)) gate insulators is reduced to just a few atomic layers, electrons can
      tunnel directly through the films. Continued device scaling will therefore
      probably require the replacement of the insulator with high-dielectric-constant
      (high-k) oxides, to increase its thickness, thus preventing tunnelling currents
      while retaining the electronic properties of an ultrathin SiO(2) film.
      Ultimately, such insulators will require an atomically defined interface with
      silicon without an interfacial SiO(2) layer for optimal performance. Following
      the first reports of epitaxial growth of AO and ABO(3) compounds on silicon, the
      formation of an atomically abrupt crystalline interface between strontium
      titanate and silicon was demonstrated. However, the atomic structure proposed for
      this interface is questionable because it requires silicon atoms that have
      coordinations rarely found elsewhere in nature. Here we describe first-principles
      calculations of the formation of the interface between silicon and strontium
      titanate and its atomic structure. Our study shows that atomic control of the
      interfacial structure by altering the chemical environment can dramatically
      improve the electronic properties of the interface to meet technological
      requirements. The interface structure and its chemistry may provide guidance for
      the selection process of other high-k gate oxides and for controlling their
      growth.

PMID- 14702082
TI  - High-latitude controls of thermocline nutrients and low latitude biological
      productivity.
AB  - The ocean's biological pump strips nutrients out of the surface waters and
      exports them into the thermocline and deep waters. If there were no return path
      of nutrients from deep waters, the biological pump would eventually deplete the
      surface waters and thermocline of nutrients; surface biological productivity
      would plummet. Here we make use of the combined distributions of silicic acid and
      nitrate to trace the main nutrient return path from deep waters by upwelling in
      the Southern Ocean and subsequent entrainment into subantarctic mode water. We
      show that the subantarctic mode water, which spreads throughout the entire
      Southern Hemisphere and North Atlantic Ocean, is the main source of nutrients for
      the thermocline. We also find that an additional return path exists in the
      northwest corner of the Pacific Ocean, where enhanced vertical mixing, perhaps
      driven by tides, brings abyssal nutrients to the surface and supplies them to the
      thermocline of the North Pacific. Our analysis has important implications for our
      understanding of large-scale controls on the nature and magnitude of low-latitude
      biological productivity and its sensitivity to climate change.

PMID- 14702083
TI  - Stability of magnesite and its high-pressure form in the lowermost mantle.
AB  - Carbonates are important constituents of marine sediments and play a fundamental
      role in the recycling of carbon into the Earth's deep interior via subduction of
      oceanic crust and sediments. Study of the stability of carbonates under high
      pressure and temperature is thus important for modelling the carbon budget in the
      entire Earth system. Such studies, however, have rarely been performed under
      appropriate lower-mantle conditions and no experimental data exist at pressures
      greater than 80 GPa (refs 3-6). Here we report an in situ X-ray diffraction study
      of the stability of magnesite (MgCO(3)), which is the major component of
      subducted carbonates, at pressure and temperature conditions approaching those of
      the core-mantle boundary. We found that magnesite transforms to an unknown form
      at pressures above approximately 115 GPa and temperatures of 2,100-2,200 K
      (depths of approximately 2,600 km) without any dissociation, suggesting that
      magnesite and its high-pressure form may be the major hosts for carbon throughout
      most parts of the Earth's lower mantle.

PMID- 14702084
TI  - Unmatched tempo of evolution in Southern African semi-desert ice plants.
AB  - The Succulent Karoo is an arid region, situated along the west coast of southern
      Africa. Floristically this region is part of the Greater Cape Flora and is
      considered one of the Earth's 25 biodiversity hotspots. Of about 5,000 species
      occurring in this region, more than 40% are endemic. Aizoaceae (ice plants)
      dominate the Succulent Karoo both in terms of species numbers (1,750 species in
      127 genera) and density of coverage. Here we show that a well-supported clade
      within the Aizoaceae, representing 1,563 species almost exclusively endemic to
      southern Africa, has diversified very recently and very rapidly. The estimated
      age for this radiation lies between 3.8 and 8.7 million years (Myr) ago, yielding
      a per-lineage diversification rate of 0.77-1.75 per million years. Both the
      number of species involved and the tempo of evolution far surpass those of any
      previously postulated continental or island plant radiation. Diversification of
      the group is closely associated with the origin of several morphological features
      and one anatomical feature. Because species-poor clades lacking these features
      occur over a very similar distribution area, we propose that these
      characteristics are key innovations that facilitated this radiation.

PMID- 14702085
TI  - A euprimate skull from the early Eocene of China.
AB  - The debut of undoubted euprimates (primates of modern aspect) was in the early
      Eocene, about 55 Myr ago. Since their first appearance, the earliest euprimates
      can be distinguished as Cantius, Donrussellia and Teilhardina. Nonetheless, the
      earliest euprimates are primarily known from isolated teeth or fragmentary jaws.
      Here we describe a partially preserved euprimate skull with nearly complete upper
      and lower dentition, which represents a new species of Teilhardina and
      constitutes the first discovery of the genus in Asia. The new species is from the
      upper section of Lingcha Formation, Hunan Province, China, with an estimated age
      of 54.97 Myr ago. Morphology and phylogeny analyses reveal that the new species
      is the most primitive species of Teilhardina, positioned near the root of
      euprimate radiation. This discovery of the earliest euprimate skull known to date
      casts new light on the debate concerning the adaptive origin of euprimates, and
      suggests that the last common ancestor of euprimates was probably a small,
      diurnal, visually oriented predator.

PMID- 14702086
TI  - Unsaturated fatty acid content in seston and tropho-dynamic coupling in lakes.
AB  - Determining the factors that control food web interactions is a key issue in
      ecology. The empirical relationship between nutrient loading (total phosphorus)
      and phytoplankton standing stock (chlorophyll a) in lakes was described about 30
      years ago and is central for managing surface water quality. The efficiency with
      which biomass and energy are transferred through the food web and sustain the
      production of higher trophic levels (such as fish) declines with nutrient loading
      and system productivity, but the underlying mechanisms are poorly understood.
      Here we show that in seston (fine particles in water) during summer, specific
      omega3-polyunsaturated fatty acids (omega3-PUFAs), which are important for
      zooplankton, are significantly correlated to the trophic status of the lake. The
      omega3-PUFAs octadecatetraenoic acid, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid, but not alpha-linolenic acid, decrease on a double
      logarithmic scale with increasing total phosphorus. By combining the empirical
      relationship between EPA-to-carbon content and total phosphorus with functional
      models relating EPA-to-carbon content to the growth and egg production of
      daphnids, we predict secondary production for this key consumer. Thus, the
      decreasing efficiency in energy transfer with increasing lake productivity can be
      explained by differences in omega3-PUFA-associated food quality at the plant
      animal interface.

PMID- 14702087
TI  - Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor
      deactivation.
AB  - The RGS proteins are GTPase activating proteins that accelerate the deactivation
      of G proteins in a variety of signalling pathways in eukaryotes. RGS9 deactivates
      the G proteins (transducins) in the rod and cone phototransduction cascades. It
      is anchored to photoreceptor membranes by the transmembrane protein R9AP (RGS9
      anchor protein), which enhances RGS9 activity up to 70-fold. If RGS9 is absent or
      unable to interact with R9AP, there is a substantial delay in the recovery from
      light responses in mice. We identified five unrelated patients with recessive
      mutations in the genes encoding either RGS9 or R9AP who reported difficulty
      adapting to sudden changes in luminance levels mediated by cones. Standard visual
      acuity was normal to moderately subnormal, but the ability to see moving objects,
      especially with low-contrast, was severely reduced despite full visual fields; we
      have termed this condition bradyopsia. To our knowledge, these patients represent
      the first identified humans with a phenotype associated with reduced RGS activity
      in any organ.

PMID- 14702088
TI  - Expression and function of orphan nuclear receptor TLX in adult neural stem
      cells.
AB  - The finding of neurogenesis in the adult brain led to the discovery of adult
      neural stem cells. TLX was initially identified as an orphan nuclear receptor
      expressed in vertebrate forebrains and is highly expressed in the adult brain.
      The brains of TLX-null mice have been reported to have no obvious defects during
      embryogenesis; however, mature mice suffer from retinopathies, severe limbic
      defects, aggressiveness, reduced copulation and progressively violent behaviour.
      Here we show that TLX maintains adult neural stem cells in an undifferentiated,
      proliferative state. We show that TLX-expressing cells isolated by fluorescence
      activated cell sorting (FACS) from adult brains can proliferate, self-renew and
      differentiate into all neural cell types in vitro. By contrast, TLX-null cells
      isolated from adult mutant brains fail to proliferate. Reintroducing TLX into
      FACS-sorted TLX-null cells rescues their ability to proliferate and to self
      renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced
      labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia
      specific expression of the astrocyte marker GFAP in neural stem cells, suggesting
      that transcriptional repression may be crucial in maintaining the
      undifferentiated state of these cells.

PMID- 14702089
TI  - On the road.

PMID- 14702090
TI  - Short-term lithium treatment promotes neuronal survival and proliferation in rat
      striatum infused with quinolinic acid, an excitotoxic model of Huntington's
      disease.
AB  - We assessed the ability of lithium to reduce neurodegeneration and to stimulate
      cell proliferation in a rat model of Huntington's disease in which quinolinic
      acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was
      injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA
      injection, lithium significantly diminished the loss of neurons immunostained for
      Neuronal Nuclei (NeuN) in the injured striatum, but failed to prevent the
      reduction of NADPH-diaphorase-positive striatal interneurons. Lithium also
      reduced the number of neurons showing DNA damage or activated caspase-3. This
      neuroprotection was associated with an upregulation of Bcl-2 protein levels in
      the striatal tissue and an increase in the number and density of Bcl-2
      immunostaining in striatal neurons. Bromodeoxyuridinie (BrdU) labeling in the
      lithium-treated injured striatum revealed the presence of large numbers of
      proliferating cells near the QA-injection site, with a reduction of BrdU-labeled
      cells in the subventricular zone (SVZ). All BrdU-labeled cells in the SVZ and the
      majority of BrdU-labeled cells near the QA-injection site were negative for
      either NeuN or glial fibrillary acidic protein (GFAP), suggesting that they are
      undifferentiated progenitor cells. However, a small number of BrdU-positive cells
      found in the QA-injected and lithium-treated striatum site were positive for
      either NeuN or GFAP. Our results suggest that lithium is neuroprotective in the
      QA-injection model of Huntington's disease not only due to its ability to inhibit
      apoptosis but also because it can stimulate neuronal and astroglial progenitor
      proliferation in the QA-injected striatum or their migration from the SVZ.

PMID- 14702098
TI  - A Method to Identify p62's UBA Domain Interacting Proteins.
AB  - The UBA domain is a conserved sequence motif among polyubiquitin binding
      proteins. For the first time, we demonstrate a systematic, high throughput
      approach to identification of UBA domain-interacting proteins from a proteome
      wide perspective. Using the rabbit reticulocyte lysate in vitro expression
      cloning system, we have successfully identified eleven proteins that interact
      with p62's UBA domain, and the majority of the eleven proteins are associated
      with neurodegenerative disorders, such as Alzheimer's disease. Therefore, p62 may
      play a novel regulatory role through its UBA domain. Our approach provides an
      easy route to the characterization of UBA domain interacting proteins and its
      application will unfold the important roles that the UBA domain plays.

PMID- 14702099
TI  - Do tumor-suppressive mechanisms contribute to organism aging by inducing stem
      cell senescence?
AB  - Stem/progenitor cells ensure tissue and organism homeostasis and might represent
      a frequent target of transformation. Although these cells are potentially
      immortal, their life span is restrained by signaling pathways (p19-p53; p16-Rb)
      that are activated by DNA damage (telomere dysfunction, environmental stresses)
      and lead to senescence or apoptosis. Execution of these checkpoint programs might
      lead to stem cell depletion and organism aging, while their inactivation
      contributes to tumor formation.

PMID- 14702100
TI  - When cells get stressed: an integrative view of cellular senescence.
AB  - Cells entering a state of senescence undergo a permanent cell cycle arrest,
      accompanied by a set of functional and morphological changes. Senescence of cells
      occurs following an extended period of proliferation in culture or in response to
      various physiologic stresses, yet little is known about the role this phenomenon
      plays in vivo. The study of senescence has focused largely on its hypothesized
      role as a barrier to extended cell division, governed by a division-counting
      mechanism in the form of telomere length. Here, we discuss the biological
      functions of cellular senescence and suggest that it should be viewed in terms of
      its role as a general cellular stress response program, rather than strictly as a
      barrier to unlimited cycles of cell growth and division. We also discuss the
      relative roles played by telomere shortening and telomere uncapping in the
      induction of senescence.

PMID- 14702101
TI  - VEGF: a critical player in neurodegeneration.
AB  - VEGF is a prototype angiogenic factor, but recent evidence indicates that this
      growth factor also has direct effects on neural cells. Abnormal regulation of
      VEGF expression has now been implicated in several neurodegenerative disorders,
      including motoneuron degeneration. This has stimulated an increasing interest in
      assessing the therapeutic potential of VEGF as a neuroprotective agent for such
      neurodegenerative disorders.

PMID- 14702102
TI  - Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of
      the nitrite anion.
AB  - While it has long been known that the reduction of nitrite to nitric oxide (NO)
      forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater
      biological activity of the nitrite anion has only recently been appreciated. In
      the stomach, NO is formed from acidic reduction of nitrite and increases mucous
      barrier thickness and gastric blood flow (see the related study beginning on page
      106). Nitrite levels in blood reflect NO production from endothelial NO synthase
      enzymes, and recent data suggest that nitrite contributes to blood flow
      regulation by reaction with deoxygenated hemoglobin and tissue heme proteins to
      form NO.

PMID- 14702103
TI  - New viruses shake old paradigms.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) can establish latent infection in
      host cells. The latently infected cells can survive and proliferate with a few
      viral genes expressed. However, in some Kaposi sarcoma cells, KSHV undergoes a
      productive life cycle and causes cell lysis. A new study (see the related article
      beginning on page 124) demonstrates that, after KSHV infection or introduction of
      viral plasmids into host cells, viral DNA is rapidly lost. Lytic virus production
      with ensuing infections could balance the loss of the viral plasmids to maintain
      the virus in cancer cells.

PMID- 14702104
TI  - East meets West: an herbal tea finds a receptor.
AB  - Jaundice, which is caused by accumulation of bilirubin, is extremely common in
      newborn infants. Phototherapy is an effective treatment, but a drug therapy would
      also be desirable. A Chinese herbal remedy for jaundice called Yin Zhi Huang is
      now shown to activate a liver receptor that enhances the clearance of bilirubin
      (see the related article beginning on page 137). This discovery could lead to
      improved pharmaceutical treatments for neonatal jaundice.

PMID- 14702105
TI  - The relative roles of growth hormone and IGF-1 in controlling insulin
      sensitivity.
AB  - IGF-1 and growth hormone (GH) interact with insulin to modulate its control of
      carbohydrate metabolism. A new study (see the related article beginning on page
      96) shows that blocking the effect of GH in the presence of low serum IGF-1
      concentrations enhances insulin sensitivity.

PMID- 14702106
TI  - Stat-3 is required for pulmonary homeostasis during hyperoxia.
AB  - Acute lung injury syndromes remain common causes of morbidity and mortality in
      adults and children. Cellular and physiologic mechanisms maintaining pulmonary
      homeostasis during lung injury remain poorly understood. In the present study,
      the Stat-3 gene was selectively deleted in respiratory epithelial cells by
      conditional expression of Cre-recombinase under control of the surfactant protein
      C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial
      cells did not alter prenatal lung morphogenesis or postnatal lung function.
      However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more
      rapidly progressive lung injury associated with alveolar capillary leak and acute
      respiratory distress. Epithelial cell injury and inflammatory responses were
      increased in the Stat-3-deleted mice. Surfactant proteins and lipids were
      decreased or absent in alveolar lavage material. Intratracheal treatment with
      exogenous surfactant protein B improved survival and lung histology in Stat-3
      deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial
      cells is not required for lung formation, but plays a critical role in
      maintenance of surfactant homeostasis and lung function during oxygen injury.

PMID- 14702107
TI  - Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo.
AB  - A central tenet of fibrinolysis is that tissue plasminogen activator-dependent (t
      PA- dependent) conversion of plasminogen to active plasmin requires the presence
      of the cofactor/substrate fibrin. However, previous in vitro studies have
      suggested that the endothelial cell surface protein annexin II can stimulate t-PA
      mediated plasminogen activation in the complete absence of fibrin. Here,
      homozygous annexin II-null mice displayed deposition of fibrin in the
      microvasculature and incomplete clearance of injury-induced arterial thrombi.
      While these animals demonstrated normal lysis of a fibrin-containing plasma clot,
      t-PA-dependent plasmin generation at the endothelial cell surface was markedly
      deficient. Directed migration of annexin II-null endothelial cells through fibrin
      and collagen lattices in vitro was also reduced, and an annexin II peptide
      mimicking sequences necessary for t-PA binding blocked endothelial cell invasion
      of Matrigel implants in wild-type mice. In addition, annexin II-deficient mice
      displayed markedly diminished neovascularization of fibroblast growth factor
      stimulated cornea and of oxygen-primed neonatal retina. Capillary sprouting from
      annexin II-deficient aortic ring explants was markedly reduced in association
      with severe impairment of activation of metalloproteinase-9 and -13. These data
      establish annexin II as a regulator of cell surface plasmin generation and reveal
      that impaired endothelial cell fibrinolytic activity constitutes a barrier to
      effective neoangiogenesis.

PMID- 14702108
TI  - Cytotoxic T lymphocytes form an antigen-independent ring junction.
AB  - Immunological synapses are organized cell-cell junctions between T lymphocytes
      and APCs composed of an adhesion ring, the peripheral supramolecular activation
      cluster (pSMAC), and a central T cell receptor cluster, the central
      supramolecular activation cluster (cSMAC). In CD8(+) cytotoxic T lymphocytes, the
      immunological synapse is thought to facilitate specific killing by confining
      cytotoxic agents to the synaptic cleft. We have investigated the interaction of
      human CTLs and helper T cells with supported planar bilayers containing ICAM-1.
      This artificial substrate provides identical ligands to CD4(+) and CD8(+) T
      cells, allowing a quantitative comparison. We found that cytotoxic T lymphocytes
      form a ring junction similar to a pSMAC in response to high surface densities of
      ICAM-1 in the planar bilayer. MICA, a ligand for NKG2D, facilitated the ring
      junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are
      upregulated in tissues by inflammation- and stress-associated signaling,
      respectively. Activated CD8(+) T cells formed fivefold more ring junctions than
      did activated CD4(+) T cells. The ring junction contained lymphocyte function
      associated antigen-1 and talin, but did not trigger polarization and granule
      translocation to the interface. This result has specific implications for the
      mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this
      process may alter CTL reactivity.

PMID- 14702109
TI  - Critical roles of TRAIL in hepatic cell death and hepatic inflammation.
AB  - The TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor
      cells but not most normal cells. Its role in hepatic cell death and hepatic
      diseases is not clear. In vitro studies suggest that murine hepatocytes are not
      sensitive to TRAIL-induced apoptosis, indicating that TRAIL may not mediate
      hepatic cell death. Using two experimental models of hepatitis, we found that
      hepatic cell death in vivo was dramatically reduced in TRAIL-deficient mice and
      mice treated with a blocking TRAIL receptor. Although both TRAIL and its death
      receptor 5 were constitutively expressed in the liver, TRAIL expression by immune
      cells alone was sufficient to restore the sensitivity of TRAIL-deficient mice to
      hepatitis. Thus, TRAIL plays a crucial role in hepatic cell death and hepatic
      inflammation.

PMID- 14702110
TI  - Triterpenoid electrophiles (avicins) activate the innate stress response by redox
      regulation of a gene battery.
AB  - Avicins are proapoptotic and anti-inflammatory triterpene electrophiles isolated
      from an Australian desert tree, Acacia victoriae. The presence of two alpha,beta
      unsaturated carbonyl groups (Michael reaction sites) in the side chain of the
      avicin molecule prompted us to study its effects on NF-E2-related factor 2
      (Nrf2), a redox-regulated transcription factor that controls the expression of a
      battery of detoxification and antioxidant proteins via its binding to antioxidant
      response element (ARE). Avicin D-treated Hep G2 cells showed translocation of
      Nrf2 into the nucleus and a time-dependent increase in ARE activity. These
      properties were sensitive to DTT, suggesting that avicins affect one or more
      critical cysteine residues, probably on the Keap1 molecule. Downstream of ARE, an
      activation of a battery of stress-induced proteins occurred. The implications of
      these findings were evaluated in vivo in mouse skin exposed to an ancient
      stressor, UV light. Avicins inhibited epidermal hyperplasia, reduced p53
      mutation, enhanced apoptosis, decreased generation of 8-hydroxy-2'
      deoxyguanosine, and enhanced expression of NADPH:quinone oxidoreductase 1 and
      heme oxygenase-1. These data, combined with our earlier published work,
      demonstrate that avicins represent a new class of plant stress metabolites
      capable of activating stress adaptation and suppressing proinflammatory
      components of the innate immune system in human cells by redox regulation. The
      relevance for treatment of clinical diseases in which stress responses are
      dysfunctional or deficient is discussed.

PMID- 14702111
TI  - Cure of prediabetic mice by viral infections involves lymphocyte recruitment
      along an IP-10 gradient.
AB  - Viruses can cause but can also prevent autoimmune disease. This dualism has
      certainly hampered attempts to establish a causal relationship between viral
      infections and type 1 diabetes (T1D). To develop a better mechanistic
      understanding of how viruses can influence the development of autoimmune disease,
      we exposed prediabetic mice to various viral infections. We used the well
      established NOD and transgenic RIP-LCMV models of autoimmune diabetes. In both
      cases, infection with the lymphocytic choriomeningitis virus (LCMV) completely
      abrogated the diabetic process. Interestingly, such therapeutic viral infections
      resulted in a rapid recruitment of T lymphocytes from the islet infiltrate to the
      pancreatic draining lymph node, where increased apoptosis was occurring. In both
      models this was associated with a selective and extensive expression of the
      chemokine IP-10 (CXCL10), which predominantly attracts activated T lymphocytes,
      in the pancreatic draining lymph node, and in RIP-LCMV mice it depended on the
      viral antigenic load. In RIP-LCMV mice, blockade of TNF-alpha or IFN-gamma in
      vivo abolished the prevention of T1D. Thus, virally induced proinflammatory
      cytokines and chemokines can influence the ongoing autoaggressive process
      beneficially at the preclinical stage, if produced at the correct location, time,
      and levels.

PMID- 14702112
TI  - Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in
      normoglycemic but not diabetic female mice.
AB  - Diabetic hyperglycemia increases ischemic brain damage in experimental animals
      and humans. The mechanisms are unclear but may involve enhanced apoptosis in
      penumbral regions. Estrogen is an established neuroprotectant in experimental
      stroke. Our previous study demonstrated that female diabetic db/db mice suffered
      less damage following cerebral hypoxia-ischemia (H/I) than male db/db mice. Here
      we investigated the effects of diabetes and estrogen apoptotic gene expression
      following H/I. Female db/db and nondiabetic (+/?) mice were ovariectomized (OVX)
      and treated with estrogen or vehicle prior to H/I; brains were analyzed for
      damage and bcl-2 family gene expression. OVX increased ischemic damage in +/?
      mice; estrogen reduced tissue injury and enhanced antiapoptotic gene expression
      (bcl-2 and bfl-1). db/db mice demonstrated more damage, without increased bcl-2
      mRNA; bfl-1 expression appeared at 48 hours of recovery associated with
      infarction. To our knowledge, this is the first description of bfl-1 in the brain
      with localization to microglia and macrophages. Early induction of bfl-1
      expression in +/? mouse brain was associated with microglia; delayed bfl-1
      expression in diabetic brain was in macrophages bordering the infarct.
      Furthermore, estrogen replacement stimulated early postischemic expression of bcl
      2 and bfl-1 and reduced damage in normoglycemic animals but failed to protect the
      diabetic brain.

PMID- 14702113
TI  - Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1
      deficient mice.
AB  - Liver IGF-1-deficient (LID) mice have a 75% reduction in circulating IGF-1 levels
      and, as a result, a fourfold increase in growth hormone (GH) secretion. To block
      GH action, LID mice were crossed with GH antagonist (GHa) transgenic mice.
      Inactivation of GH action in the resulting LID + GHa mice led to decreased blood
      glucose and insulin levels and improved peripheral insulin sensitivity.
      Hyperinsulinemic-euglycemic clamp studies showed that LID mice exhibit severe
      insulin resistance. In contrast, expression of the GH antagonist transgene in LID
      + GHa mice led to enhanced insulin sensitivity and increased insulin-stimulated
      glucose uptake in muscle and white adipose tissue. Interestingly, LID + GHa mice
      exhibit a twofold increase in white adipose tissue mass, as well as increased
      levels of serum-free fatty acids and triglycerides, but no increase in the
      triglyceride content of liver and muscle. In conclusion, these results show that
      despite low levels of circulating IGF-1, insulin sensitivity in LID mice could be
      improved by inactivating GH action, suggesting that chronic elevation of GH
      levels plays a major role in insulin resistance. These results suggest that IGF-1
      plays a role in maintaining a fine balance between GH and insulin to promote
      normal carbohydrate and lipid metabolism.

PMID- 14702114
TI  - Nitrite in saliva increases gastric mucosal blood flow and mucus thickness.
AB  - Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral
      bacteria. In the acidic stomach, nitrite is further reduced to NO and related
      compounds, which have potential biological activity. We used an in vivo rat model
      as a bioassay to test effects of human saliva on gastric mucosal blood flow and
      mucus thickness. Gastric mucosal blood flow and mucus thickness were measured
      after topical administration of human saliva in HCl. The saliva was collected
      either after fasting (low in nitrite) or after ingestion of sodium nitrate (high
      in nitrite). In additional experiments, saliva was exchanged for sodium nitrite
      at different doses. Mucosal blood flow was increased after luminal application of
      nitrite-rich saliva, whereas fasting saliva had no effects. Also, mucus thickness
      increased in response to nitrite-rich saliva. The effects of nitrite-rich saliva
      were similar to those of topically applied sodium nitrite. Nitrite-mediated
      effects were associated with generation of NO and S-nitrosothiols. In addition,
      pretreatment with an inhibitor of guanylyl cyclase markedly inhibited nitrite
      mediated effects on blood flow. We conclude that nitrite-containing human saliva
      given luminally increases gastric mucosal blood flow and mucus thickness in the
      rat. These effects are likely mediated through nonenzymatic generation of NO via
      activation of guanylyl cyclase. This supports a gastroprotective role of salivary
      nitrate/nitrite.

PMID- 14702115
TI  - Activation of caspase-3 is an initial step triggering accelerated muscle
      proteolysis in catabolic conditions.
AB  - With trauma, sepsis, cancer, or uremia, animals or patients experience
      accelerated degradation of muscle protein in the ATP-ubiquitin-proteasome (Ub
      P'some) system. The initial step in myofibrillar proteolysis is unknown because
      this proteolytic system does not break down actomyosin complexes or myofibrils,
      even though it degrades monomeric actin or myosin. Since cytokines or insulin
      resistance are common in catabolic states and will activate caspases, we examined
      whether caspase-3 would break down actomyosin. We found that recombinant caspase
      3 cleaves actomyosin, producing a characteristic, approximately 14-kDa actin
      fragment and other proteins that are degraded by the Ub-P'some. In fact, limited
      actomyosin cleavage by caspase-3 yields a 125% increase in protein degradation by
      the Ub-P'some system. Serum deprivation of L6 muscle cells stimulates actin
      cleavage and proteolysis; insulin blocks these responses by a mechanism requiring
      PI3K. Cleaved actin fragments are present in muscles of rats with muscle atrophy
      from diabetes or chronic uremia. Accumulation of actin fragments and the rate of
      proteolysis in muscle stimulated by diabetes are suppressed by a caspase-3
      inhibitor. Thus, in catabolic conditions, an initial step resulting in loss of
      muscle protein is activation of caspase-3, yielding proteins that are degraded by
      the Ub-P'some system. Therapeutic strategies could be designed to prevent these
      events.

PMID- 14702116
TI  - Inefficient establishment of KSHV latency suggests an additional role for
      continued lytic replication in Kaposi sarcoma pathogenesis.
AB  - Kaposi sarcoma-associated (KS-associated) herpesvirus (KSHV) infection is linked
      to the development of both KS and several lymphoproliferative diseases. In all
      cases, the resulting tumor cells predominantly display latent viral infection. KS
      tumorigenesis requires ongoing lytic viral replication as well, however, for
      reasons that are unclear but have been suggested to involve the production of
      angiogenic or mitogenic factors by lytically infected cells. Here we demonstrate
      that proliferating cells infected with KSHV in vitro display a marked propensity
      to segregate latent viral genomes, with only a variable but small subpopulation
      being capable of stable episome maintenance. Stable maintenance is not due to the
      enhanced production of viral or host trans-acting factors, but is associated with
      cis-acting, epigenetic changes in the viral chromosome. These results indicate
      that acquisition of stable KSHV latency is a multistep process that proceeds with
      varying degrees of efficiency in different cell types. They also suggest an
      additional role for lytic replication in sustaining KS tumorigenesis: namely, the
      recruitment of new cells to latency to replace those that have segregated the
      viral episome.

PMID- 14702118
TI  - [Do ketolides have real advantages over macrolides?].

PMID- 14702117
TI  - A traditional herbal medicine enhances bilirubin clearance by activating the
      nuclear receptor CAR.
AB  - Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other
      herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently
      identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator
      of bilirubin clearance in the liver. Here we show that treatment of WT and
      humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the
      clearance of intravenously infused bilirubin. This effect is absent in CAR
      knockout animals. Expression of bilirubin glucuronyl transferase and other
      components of the bilirubin metabolism pathway is induced by Yin Zhi Huang
      treatment of WT mice or mice expressing only human CAR, but not CAR knockout
      animals. 6,7-Dimethylesculetin, a compound present in Yin Chin, activates CAR in
      primary hepatocytes from both WT and humanized CAR mice and accelerates bilirubin
      clearance in vivo. We conclude that CAR mediates the effects of Yin Zhi Huang on
      bilirubin clearance and that 6,7-dimethylesculetin is an active component of this
      herbal medicine. CAR is a potential target for the development of new drugs to
      treat neonatal, genetic, or acquired forms of jaundice.

PMID- 14702119
TI  - [Pharmacology of antimicrobials used in the treatment of serious Gram-positive
      bacteria infections].
AB  - Antimicrobials with specific activity against Gram-positive cocci (glycopeptides,
      oxazolidinones and streptogramins) have pharmacokinetic differences that are
      important to know. Linezolid and teicoplanin can be administered extravascularly
      due to their good bioavailability, allowing their use as sequential therapy in
      patients requiring prolonged treatment. All of these antimicrobials have an
      adequate distribution in extracellular tissues, even teicoplanin, due to the
      balance between the fraction that is bound and unbound to plasma proteins and its
      long terminal half-life. As the elimination of glycopeptides is almost
      exclusively renal, it is necessary to perform a posology adjustment in patients
      with renal failure. Quinupristin/dalfopristin and linezolid are metabolized by
      the liver, but CYP450 is only involved in streptogramin elimination.

PMID- 14702120
TI  - [Influence of consensual protocols on the use of antibiotics and bacterial
      resistance in a general hospital. A prospective study 1995-2000].
AB  - Reasoned and consensual protocols, by means of diversification of the use of
      antibiotics, significantly influence their consumption, preventing and reducing
      the development of bacterial resistance against the Gram-negative microorganisms
      most frequently isolated in general hospitals. The increase in the consumption of
      piperacillin-tazobactam was found to be significantly associated with an
      increased resistance of E. cloacae, but less so in K. pneumoniae and E. coli. Its
      activity against P. aeruginosa and against P. mirabilis was not affected
      throughout the study and it maintained a high sensivity to the end against P.
      aeruginosa and against P. mirabilis and partial recovery of activity against A.
      baumannii. No statistically significant differences were found between the stable
      consumption of cefotaxime, ciprofloxacin, ceftazidime and imipenem and bacterial
      resistance against E. coli, P. aeruginosa, P. mirabilis, K. pneumoniae, E.
      cloacae and A. baumannii. Imipenem presented greater activity against E. coli, K.
      pneumoniae, E. cloacae and A. baumannii. Piperacillin-tazobactam showed greater
      activity against P. aeruginosa, while ciprofloxacin showed the least activity
      against E. coli and P. mirabilis. Cefotaxime had the least activity against E.
      cloacae, P. aeruginosa and A. baumannii. Ceftazidime showed stable activity and
      was similar to piperacillin-tazobactam against E. coli, P. mirabilis, K.
      pneumoniae, E. cloacae and A. baumannii.

PMID- 14702121
TI  - [Pharmacoeconomic analysis of community-acquired pneumonia treatment with
      telithromycin or clarithromycin].
AB  - A pharmacoeconomic analysis was carried out comparing the efficacy of two
      treatment options for community-acquired pneumonia (CAP): telithromycin and
      clarithromycin. It was a retrospective analysis using a decision tree model. The
      efficacy of the two treatment options was estimated from a randomized, double
      blind clinical trial, in which 800 mg/day oral telithromycin for 10 days was
      compared to 1000 mg/day oral clarithromycin for 10 days in patients with CAP (162
      and 156 respectively). The use of resources was estimated based on the clinical
      trial and Spanish sources, and the unit costs from a Spanish health costs
      database. Costs were evaluated for the acquisition of antibiotic treatments,
      change of antibiotic due to therapeutic failure, hospital admissions, adverse
      reactions to treatment, primary care visits, tests and indirect costs (working
      days lost). The model was validated by a panel of Spanish clinical experts. As
      the clinical trial was designed to show equivalence, there were no significant
      differences in efficacy between the treatment options (clinical cure rate 88.3%
      and 88.5%, respectively), and a cost minimization analysis was performed. In the
      base case, the average cost of the disease per patient was 308.29 euros with
      telithromycin and 331.5 euros with clarithromycin (a difference of 23.21 euros).
      The results were stable in the susceptibility analysis, with differences
      favorable to telithromycin ranging between 5.50 and 45.45 euros. Telithromycin
      results in a cost savings of up to 45.45 euros per CAP patient compared to
      clarithromycin.

PMID- 14702122
TI  - [Methicillin resistant Staphylococcus aureus from clinical samples in Cordoba
      (Spain)].
AB  - Increases in methicillin-resistant Staphylococcus aureus (MRSA) strains and in
      isolates with reduced susceptibility to glucopeptides have become an important
      problem in the epidemiology of Gram-positive microorganisms. All the consecutive
      S. aureus collected in our hospital from 1995 to 2001 were studied. Of the 4531
      isolates 24.23% were methicillin resistant in this period. The highest number of
      methicillin-resistant strains were found in wound exudates. In recent years an
      almost 20% increase in MRSA has occurred in our hospital. As MRSA strains are an
      important problem in our area and their prevalence is on the rise, as is
      multiresistance, the monitoring and control of MRSA strains in our hospitals is
      necessary.

PMID- 14702123
TI  - [Resistance of HIV-1 to antiretroviral drugs in Valencia (Spain): mutations and
      susceptibility].
AB  - Resistance of HIV to antiretroviral drugs was studied in 210 samples taken in the
      last two years from patients at the Molecular Biology Unit of the Microbiology
      Department of the Hospital La Fe in Valencia, Spain. Once the viral load in
      plasma was determined, resistance was detected using complete gene sequencing for
      protease until position 3464 of the HIV-1 inverse transcriptase gene. The results
      were analyzed using the programs Omiga 1.2 (Oxford Molecular Group) and HR-ASAP
      1.0 (Stanford University). The protease inhibitors the least affected by the
      presence of mutations leading to resistance were amprenavir (68.96% activity),
      and lopinavir (70.69% activity), and of the inverse transcriptase inhibitors,
      tenofovir (94.02% activity), D4T (74.62% activity) and 3TC (76.12% activity). The
      treatment combination with the greatest activity, based on the different
      mutations, was D4T + 3TC + NNRTI. To justify the persistence of viremia with
      relatively low genotypic resistance to antiretroviral drugs other variables must
      be considered, such as treatment compliance and the pharmacokinetics of the
      drugs.

PMID- 14702124
TI  - [Meta-analysis of clarithromycin compared with other antimicrobial drugs in the
      treatment of upper respiratory tract infections].
AB  - The goal of this meta-analysis was to evaluate the effectiveness of
      clarithromycin versus most commonly used treatments for upper respiratory
      infections. We performed a systematic review of comparative clinical trials found
      in the literature. Regarding effectiveness, no significant differences were found
      in comparisons between clarithromycin and amoxicillin-clavulanic acid for upper
      respiratory infections, nor for cephalosporins, amoxicillin or amoxicillin
      clavulanic acid for otitis media, nor oral penicillin for classic streptococcal
      tonsillitis. Clarithromycin was more effective than betalactam antibiotics for
      sinusitis (OR: 1.27, 95% CI: 1.01-1.61 in intent-to-treat analysis). The
      effectiveness of clarithromycin was better than that for azithromycin, but only
      reached statistical significance in the per-protocol analysis. The global
      analysis including all 33 clinical trials showed a small benefit for
      clarithromycin reaching statistical significance in the fixed-effects model (OR:
      1.12, 95% CI: 1.01-1.25). Regarding safety, the incidence of adverse events was
      significantly lower for clarithromycin compared to amoxicillin and amoxicillin
      clavulanic acid. No differences were found when comparing adverse events due to
      cephalosporins, azithromycin and betalactam antibiotics, but the incidence of
      adverse events for clarithromycin was higher compared to that of oral penicillin
      for streptococcal tonsillitis treatment. Overall, all the compared drugs were
      well tolerated; discontinuations due to adverse events were very low: 2.2% for
      clarithromycin treatment and 2.5% for the other antibiotics. It was concluded
      that clarithromycin is an effective and safe treatment for upper respiratory
      infection, and its new formulation in a single daily dose may improve therapeutic
      compliance.

PMID- 14702125
TI  - [Hepatitis C virus variability and interferon-mediated pathway inhibition].
AB  - The most important aim of this study was to describe the hypothetical
      relationship between the PePHD region variability (related to the synthesis of a
      cellular enzyme pseudosubstrate) of the hepatitis C virus and the response of
      patients to interferon therapy. This interaction could be a determining factor in
      the antiviral effect of interferon. All samples (from 24 patients with chronic
      hepatitis C infection) were analyzed using a previously described method based on
      RT-PCR and nested PCR mediated by single-strand conformation polymorphism assay
      (SSCP). The patients were divided into three groups with respect to the response
      to therapy: 8 patients with sustained response, 8 patients with transient
      response and 8 nonresponders. In all samples a low genetic heterogeneity pattern
      was detected, which was independent of other factors involved in the lack of
      response to treatment, such as age, sex or viral genotype. This genetic
      homogeneity is an indirect indication of the importance of the region on viral
      persistence. However, more studies are needed to evaluate the real role of this
      sequence on the interaction between cells and the virus.

PMID- 14702126
TI  - [Study of the susceptibility of Streptococcus pneumoniae in La Rioja].

PMID- 14702127
TI  - [Prevention of perinatal group B streptococcal infection. Revised Spanish
      guidelines].

PMID- 14702128
TI  - [Treatment of infections related to long-term venous catheters].

PMID- 14702129
TI  - Ocular side effects associated with bisphosphonates.
AB  - Bisphosphonates are used to inhibit bone resorption in postmenopausal women and
      in the management of hypercalcemia of malignancy. Recently, some drugs within
      this class of medicines have been proven to cause scleritis. Prior to this,
      bisphosphonates had been reported to cause a variety of ocular side effects, most
      of which are inflammatory. This review discusses the many different medicines
      called bisphosphonates and highlights the ocular side effect profile of each. In
      cases where information on dechallenge is provided, all the ocular side effects
      resolved after discontinuation of the medication. Recognition of adverse ocular
      events in association with bisphosphonate therapy should alert clinicians to the
      need for ophthalmic evaluation and the consideration of discontinuation of
      therapy in all cases of scleritis.

PMID- 14702130
TI  - Research into molecular and genetic mechanisms underlying prostate carcinogenesis
      would be greatly advanced by in vitro prostate cell models.
AB  - Prostate cancer is the most commonly diagnosed malignancy in the United States,
      as well as in the Western world, and the second leading cause of male cancer
      death in the United States. Despite its high incidence, the molecular and genetic
      events involved in prostate cancer progression remain poorly understood. A hurdle
      in understanding the molecular genetic changes in prostate cancer has been the
      difficulty in establishing premalignant lesions and primary prostate tumors as in
      vitro cell cultures. Primary epithelial cells grow for a finite life span and
      then senesce. Immortalization is defined by continuous growth of otherwise
      senescing cells and is believed to represent an early stage in tumor progression.
      In order to examine these early stages, we and others have developed in vitro
      models of prostate epithelial cell immortalization. Because prostate cancer is a
      multistep, progressive disease with a typical onset later in life and with an
      usually high number of latent cases that do not develop into clinically manifest
      cancer, the steps in the progression to malignancy are of particular interest. To
      understand the many factors that are suspected to contribute to the development
      of this malignancy, there is a need for an in vitro multistep human prostate
      epithelial culture system. These models have been extremely important in
      identifying genetic and molecular changes involved in prostate cancer
      progression. Recently, novel human cell culture models for the study of prostate
      cancer have been developed. Successful establishment of primary prostate cancer
      cell lines from patients' familial and sporadic prostate cancer has been
      accomplished using telomerase, the gene that prevents cellular senescence. The
      novel models will be useful for identification and characterization of prostate
      cancer genes and will provide the new means for testing for chemoprevention and
      chemotherapeutic agents.

PMID- 14702131
TI  - New therapeutic strategies in allergic diseases.
AB  - During the past 10 years, strong evidence has been provided to suggest that type
      2 T herpes (Th2) responses to 'innocuous' environmental antigens (allergens) play
      a critical triggering role in the development of allergic disorders. The
      important role of Th2 cytokines, IL-4, IL-5, IL-9, IL-13, in accounting for most
      pathophysiological manifestations of atopic allergy has been largely clarified by
      a series of studies performed in both human diseases and experimental animal
      models of allergy and asthma. Moreover, the mechanisms responsible for Th2
      polarized responses against allergens in atopic subjects, as well as the nature
      of transcription factors involved in the Th2 polarization, have been identified.
      Likewise, the role of chemoattractants and chemoattractant receptors, as well as
      of adhesion molecules, in favoring and amplifying the allergic inflammation has
      been established. The new insights into the pathophysiology of T cell responses
      in atopic diseases are providing exciting opportunities for the development of
      novel immunotherapeutic strategies. These include either nonallergen-specific or
      allergen-specific regimens. In patients with severe atopic disorders, the
      possibility of nonallergen-specific strategies designed to target Th2 cells;
      molecules involved in Th2 differentiation, such as Th2-selective transcription
      factors, or Th2-dependent effector molecules, such as Th2 cytokines, IL-4, IL-5,
      IL-9, and IL-13; Th2-related chemokines and/or receptors, or IgE antibody, are
      being considered. In the majority of atopic subjects affected by mild or moderate
      allergic diseases, allergen-specific immunotherapies probably would be better. To
      that end, there are presently two main lines of research, one based on the
      induction of immune suppression and the other on the redirection of allergen
      specific Th2 cell responses to a less polarized profile of cytokine production
      (immune deviation).

PMID- 14702132
TI  - Insulin glargine versus NPH insulin in patients with type 1 diabetes.
AB  - Type 1 diabetes is associated with a number of diabetes-related complications
      which may be minimized by maintaining good long-term metabolic control. The
      current guidelines recommend that glycosylated hemoglobin levels should be
      targeted to below 7.0% or 6.5% to reduce the incidence of diabetic complications,
      including micro- and macrovascular disorders. However, this intensive metabolic
      control is hindered by the occurrence of hypoglycemia. The episodes of
      hypoglycemia are problematic for patients taking intermediate-acting insulin
      preparations (i.e., NPH insulin), which have traditionally formed the mainstay
      basal insulin treatment. With NPH insulin, the pharmacokinetic profile is such
      that peak insulin activity occurs 4-6 hours following administration; therefore,
      nocturnal hypoglycemia commonly takes place after bedtime administration of the
      insulin. The development of the long-acting human insulin analogue insulin
      glargine now provides patients with an insulin that offers a longer duration of
      action (up to 24 hours) and a smoother time-action profile compared with those of
      NPH insulin. A number of clinical trials comparing the safety and efficacy of
      insulin glargine and NPH insulin in patients with type 1 diabetes show that, in
      addition to other clinical benefits over NPH insulin, insulin glargine may also
      improve glycemic control and satisfaction in this patient population.

PMID- 14702133
TI  - Ibandronate: new options in the treatment of osteoporosis.
AB  - Bisphosphonates are currently considered the treatment of choice for
      corticosteroid-induced male osteoporosis and represent one of the options for the
      prevention and treatment of postmenopausal osteoporosis. The treatment of
      osteoporosis with antiresorbing agents requires long-lasting or even lifelong
      therapies. Oral bisphosphonates are reasonably well tolerated, but a sizable
      proportion of patients report esophageal symptoms which are occasionally severe.
      In addition, their intestinal absorption is only 0.5-1% and the presence of any
      residual food in the stomach completely blocks absorption. Intravenous
      bisphosphonate administration, which avoids the upper gastrointestinal
      tolerability concerns associated with oral regimens, may be of considerable value
      for many patients such as elderly and institutionalized patients because it
      ensures full treatment compliance, but the intravenous route has to be used with
      caution since acute renal failure has been observed following the intravenous
      administration of several bisphosphonates and prolonged intravenous infusions can
      also be potentially associated with thrombotic complications and infections.
      Bisphosphonate dosing by intravenous injection could provide a convenient
      alternative to intravenous infusion that would be suitable for use in the primary
      care setting and would avoid many of the complications associated with prolonged
      infusions. This option is viable with the highly potent, nitrogen-containing
      bisphosphonates such as ibandronate, which, unlike other lower potency
      bisphosphonates, can be administered as an intravenous injection of only a few
      milligrams in regimens with extended between-dose intervals. In this review, the
      data obtained with ibandronate, using both oral administration and intravenous
      injection, for the treatment and prevention of postmenopausal osteoporosis are
      summarized.

PMID- 14702134
TI  - Treatment of antidepressant-induced sexual dysfunction.
AB  - This article reviews the prevalence of antidepressant-induced sexual dysfunction
      and the strategies available for managing sexual adverse events. A high incidence
      of sexual dysfunction has been observed in patients treated with antidepressants.
      In particular, it has been reported in more than half of the patients treated
      with selective serotonin reuptake inhibitors. There are various
      pharmacotherapeutic strategies that can lead to reversal of sexual dysfunction.
      This article will review clinical studies on pharmacotherapeutic agents used to
      treat antidepressant-induced sexual dysfunction, as well as agents used to treat
      depression with a favorable sexual side-effect profile. Because sexual
      dysfunction can lead to treatment noncompliance and depression relapse, this is
      an issue that should be addressed by clinicians at initiation and throughout the
      course of treatment.

PMID- 14702135
TI  - The role of CCK2 receptors in the homeostasis of the opioid system.
AB  - The overlapping distribution of opioid and cholecystokinin (CCK) peptides and
      their receptors (mu- and delta-opioid receptors, CCK1 and CCK2 receptors) in the
      central nervous system have led to a large number of studies aimed at clarifying
      the functional relationships between these two neuropeptides. The existence of
      regulatory loops between both systems has been proposed, and the physiological
      antagonism between CCK, through activation of CCK2 receptors, and endogenous
      opioid systems has been demonstrated. This is illustrated by the large
      potentiation of the main pharmacological effects of exogenous (morphine) or
      endogenous (enkephalins) opioids. Thus, co-administration of CCK2 antagonists
      with morphine or RB-101, a systemically active inhibitor which fully protects
      enkephalins from their degradation, led to strongly enhanced analgesic responses
      or antidepressant-like effects of the opioids. All these findings have been
      recently confirmed using CCK2 receptor knockout mice, and the role of CCK2
      receptor in the physiological control of the opioid system has been conclusively
      demonstrated. In this article, we review the experimental pharmacology of the
      association of CCK2 antagonists and opioids (exogenous and endogenous),
      emphasizing the clinical interest of such an association.

PMID- 14702136
TI  - Glycogen synthase kinase-3 as drug target: from wallflower to center of
      attention.
AB  - Some 20 years ago, glycogen synthase kinase-3 (GSK-3) was categorized as one of
      several protein kinases that could phosphorylate glycogen synthase and regulate
      the glucose metabolism pathway. Today, GSK-3 is being identified as a ubiquitous
      serine/threonine protein kinase that participates in a multitude of cellular
      processes, ranging from cell membrane-to-nucleus signaling, gene transcription,
      translation, cytoskeletal organization to cell cycle progression and survival.
      Two functional aspects make GSK-3 a peculiar kinase: its activity is constitutive
      and downregulated after cell activation by phosphorylation or interaction with
      inhibitory proteins, and the enzyme prefers substrates that are specifically
      prepared, that is prephosphorylated, by other kinases. Its pleiotropic but unique
      activities have made GSK-3 a much sought-after target for the treatment of
      prevalent human diseases such as type 2 diabetes and Alzheimer's disease. Recent
      drug discovery efforts have identified small-molecule, orally active inhibitors
      of GSK-3. This accomplishment may represent the first step toward the development
      of novel therapeutic agents.

PMID- 14702137
TI  - Smart nanotubes for biomedical and biotechnological applications.
AB  - Nanoparticles are being developed for a host of biomedical and biotechnological
      applications including drug delivery, enzyme immobilization and DNA transfection.
      Spherical nanoparticles are typically used for such applications, but this only
      reflects the fact that spheres are easier to make than other shapes. Micro- and
      nanotubes--structures that resemble tiny drinking straws--are alternatives and
      may offer advantages over spherical nanoparticles for some applications. This
      article discusses four different approaches to making micro- and nanotubes and
      reviews the current status of efforts to develop biomedical and biotechnological
      applications of these tubular structures.

PMID- 14702138
TI  - The role of CD1-mediated presentation of myelin lipids in experimental autoimmune
      encephalomyelitis and multiple sclerosis pathologenesis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system characterized by the destruction of the myelin sheath surrounding axons.
      On the basis of data from the animal model, experimental autoimmune
      encephalomyelitis (EAE) and the detection of myelin-reactive cells in MS
      patients, this destruction is thought to be due to an autoimmune T-cell-mediated
      response to myelin antigens. Until recently, the characterization of T-cell
      recognition of myelin antigens has necessarily focused on the response to myelin
      proteins. However, the discovery of CD1-mediated presentation of lipids and
      glycolipids to a variety of T-cell populations has greatly expanded the
      repertoire of antigens to which T cells can respond. Studies in the EAE model
      suggest a role for myelin lipids in disease pathogenesis. Recent characterization
      of the expression and function of CD1 and the responding T-cell populations does
      support a role for this pathway in the disease process. Furthermore, data suggest
      that it may be possible to modulate the disease course by targeting this pathway.
      Characterization of CD1-mediated presentation of lipids to T cells has only
      recently been investigated in MS, with most attention focusing on the expression
      of group I CD1 proteins in MS lesions. In light of data from the animal model,
      further characterization of the expression and function of group I and group II
      CD1 proteins is warranted, and could lead to the development of effective
      therapies to treat MS.

PMID- 14702139
TI  - GATA transcription factors and fat cell formation.
AB  - GATA transcription factors play important roles in a variety of developmental
      processes. Recently, we discovered that GATA factors also play a key role in
      adipogenesis. Two isoforms, GATA-2 and GATA-3, are specifically expressed in
      murine preadipocytes but not mature adipocytes. Continuous expression of GATA
      factors in preadipocyte cell lines inhibits terminal differentiation into mature
      adipocytes. In contrast, GATA-3-deficient mouse embryonic stem cells possess a
      higher capacity to convert to adipocytes. The inhibitory effect of GATA on
      adipogenesis is mediated in part by suppression of promoters of adipogenic
      factors, including peroxisome proliferator-activated receptor gamma, but
      additional mechanisms are also likely to be in effect. These findings indicate
      that GATA factors function as molecular gatekeepers at the onset of terminal
      adipocyte differentiation. Whether GATA factors are also involved in the
      commitment of multipotent mesenchymal stem cells to progenitors of the adipogenic
      lineage is under investigation.

PMID- 14702140
TI  - The role of bone morphogenetic proteins in sympathetic neuron development.
AB  - The generation of specific neuronal subtypes from neural stem cells is one of the
      dominating themes in developmental neurobiology. In the last years, key signaling
      pathways have been identified that are involved in the generic control of
      neurogenesis. In addition, genes were found that selectively control the
      specification and differentiation of specific types of neurons. The development
      of sympathetic neurons from neural crest-derived precursors has been investigated
      over the years in great detail at molecular and cellular levels and thus
      represents one of the best understood models of neuron generation. The present
      review summarizes results demonstrating the role of the extrinsic signaling
      molecules, bone morphogenetic proteins (BMPs), and of their downstream
      transcription factors in the generation and differentiation of noradrenergic
      sympathetic neurons. How these signaling pathways are modified to generate other
      nonnoradrenergic neuron types of the autonomic nervous system is discussed in the
      context of recent studies of the development of parasympathetic neurons. Finally,
      evidence is reviewed that implicates BMPs at later stages of sympathetic neuron
      differentiation, in the control of dendrite formation.

PMID- 14702141
TI  - The adenosine A(2A) receptor as an attractive target for Parkinson's disease
      treatment.
AB  - Long-term L-dopa treatment of Parkinson's disease can lose its effectiveness and
      cause development of motor complications such as dyskinesia. Furthermore, L-dopa
      therapy does not address the fundamental pathological process of dopaminergic
      neurodegeneration in Parkinson's disease. This prompts a search for an
      alternative or complementary therapy for Parkinson's disease to overcome these
      limitations. During the last 5 years, the adenosine A(2A) receptor has emerged as
      an attractive target for Parkinson's disease therapy, primarily because of its
      localized expression in striatum and motor enhancement function. Recent genetic
      and pharmacological studies indicate that A(2A) receptor antagonists also offer
      neuroprotective effects and may possibly modify chronic L-dopa-induced
      maladaptive responses in animal models of Parkinson's disease. This review
      summarizes multiple potential benefits of the A(2A) receptor blockade in treating
      the motor symptoms as well as the underlying dopaminergic neurodegeneration of
      Parkinson's disease.

PMID- 14702142
TI  - Molecular mechanism of neuropathic pain.
AB  - Pain is the most common clinical symptom for which people seek medical care.
      Although effective therapy for inflammatory pain is possible, current therapy for
      neuropathic pain is still inadequate. Even the strongest painkiller, morphine, is
      reported to be ineffective against neuropathic pain in the clinic. The lack of
      effective therapeutic agents for neuropathic pain is due to the fact that its
      underlying mechanisms are still not fully understood. Recently, pain researchers
      have been trying to identify the cellular and molecular processes that lead to
      neuropathic pain. Understanding the molecular mechanisms of neuropathic pain
      would certainly provide a hope for the future development of effective therapies
      for this intractable painful disease.

PMID- 14702143
TI  - Molecule of the month. Exenatide.

PMID- 14702144
TI  - Pharmacotherapy for neuropathic pain: progress and prospects.
AB  - Neuropathic pain, a persistent chronic pain resulting from damage to the central
      or peripheral pain signaling pathway, has become an area of intense research
      activity--largely because it represents a disorder with high unmet medical need.
      It is not a single disease entity, but rather includes a range of heterogeneous
      conditions that differ in etiology, location and initiating cause. Despite this
      diversity, the clinical presentation is frequently surprisingly similar, which
      suggests a common biological basis. Until recently, little was known of the
      mechanisms underlying the various neuropathic pain conditions, making the
      directed development of novel therapies almost impossible. However, the steady
      increase in our understanding of the anatomical, cellular and molecular basis of
      neuropathic pain, coupled with the advent of a number of experimental models of
      neuropathy, has permitted relatively rapid progress, and the prospects for the
      emergence of new, more effective therapies look very good. Gabapentin (Pfizer),
      which appears to act by blocking calcium channels, is the first drug to acquire
      widespread regulatory approval for the treatment of neuropathic pain. The Society
      for Medicines Research symposium held June 26, 2003, considered this treatment
      modality alongside other approaches to therapy, such as N-methyl-D-aspartate
      receptor antagonists and cannabinoid receptor agonists. The whole meeting
      provided an excellent description of the challenges facing neuropathic pain drug
      discovery--at both the research and the development phases of the value chain.

PMID- 14702145
TI  - Happy birthday to us!! JID reaches 100.

PMID- 14702146
TI  - Hepatitis C virus (HCV) occult infection or occult HCV RNA detection?

PMID- 14702147
TI  - Occult hepatitis C virus infection in patients in whom the etiology of
      persistently abnormal results of liver-function tests is unknown.
AB  - BACKGROUND: There are patients in whom the etiology of long-standing abnormal
      results of liver-function tests is unknown (ALF-EU) after exclusion of all known
      causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA
      in liver-biopsy specimens from 100 patients who were negative for anti-HCV
      antibodies and for serum HCV RNA and who had ALF-EU. METHODS: HCV RNA status was
      tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ
      hybridization, in liver and peripheral-blood mononuclear cells (PBMCs). RESULTS:
      HCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative
      for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV
      infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of
      these 57 patients with occult HCV infection. Nucleotide-sequence analysis
      confirmed the specificity of detection of HCV RNA and that patients were infected
      with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40
      (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with
      occult HCV infection were more likely to have necroinflammatory activity (P=.017)
      and fibrosis (P=.022) than were patients without intrahepatic HCV RNA.
      CONCLUSIONS: Patients with ALF-EU may have intrahepatic HCV RNA in the absence of
      anti-HCV antibodies and of serum HCV RNA.

PMID- 14702148
TI  - Elevated seroprevalence of human herpesvirus 8 among men with prostate cancer.
AB  - Background. To investigate any epidemiological association between human
      herpesvirus (HHV)-8 and prostate cancer, we determined the prevalence of HHV-8
      seropositivity among prostate cancer case and control subjects in the United
      States and Trinidad and Tobago.Methods. Antibodies against HHV-8 were detected in
      2 independent laboratories using either indirect immunofluorescence assay (IFA)
      or a combination of enzyme-linked immunosorbent assay and IFA.Results. Among 138
      Tobago men with prostate cancer, HHV-8 seroprevalence was 39.9%-significantly
      higher than that among 140 age-matched control subjects (22.9%; P=.003; odds
      ratio [OR], 2.24; 95% confidence interval [CI], 1.29-3.90). Among 100 US men with
      prostate cancer, seroprevalence was 20%-significantly higher than that of 177
      blood donors (5.1%; P=.001; OR, 4.67; 95% CI, 1.91-11.65) and higher than that of
      99 men with cancer not related to HHV-8 (13%; P=.253; 95% CI, 0.77
      3.54).Conclusions. HHV-8 seropositivity is elevated among men with prostate
      cancer compared with control subjects, which suggests that HHV-8 plays a role in
      the development of prostate cancer.

PMID- 14702149
TI  - Detection of noroviruses in water--summary of an international workshop.
AB  - Noroviruses (NVs) are the most common cause of acute nonbacterial gastroenteritis
      worldwide. An international workshop of 36 people from 5 countries was held on 20
      22 March 2002, in Voorhees, New Jersey, to identify barriers to the development
      of methods for detection of NVs in water and to develop a multiyear research
      agenda to coordinate efforts to advance the development of methods for detection
      of NVs. The workshop focused on 3 areas: (1) collection, concentration, and
      processing of samples; (2) molecular methods for detection and confirmation of
      NVs; and (3) the detection of infectious NVs through cell culture, infectivity
      surrogates, and human volunteers. Twelve research projects were developed by the
      workshop participants.

PMID- 14702150
TI  - Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration
      in T cell phenotype after interferon-alpha therapy for HTLV-I-associated
      myelopathy/tropical spastic paraparesis.
AB  - To analyze the mechanism by which interferon (IFN)-alpha is effective against
      human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP), we investigated the T cell phenotype and HTLV-I
      provirus load in peripheral blood mononuclear cells from 25 patients with HAM/TSP
      that were obtained before and after administration of IFN-alpha. The frequency of
      memory (CD45RA(-)CD27(+)) T cells that were CD8(high+), CXCR3(+) cell
      populations, and HTLV-I provirus loads were significantly decreased after
      treatment. The proportion of memory T cells in the CD8(high+) cell population
      correlated well with HTLV-I provirus load, whereas the proportion of effector
      (CD45RA(+)CD27(-)) cells in the CD8(high+) cell population was inversely
      correlated with provirus load. Interestingly, the frequency of perforin
      expression in CD8(high+) cells was significantly decreased after treatment in
      patients who experienced clinical improvement, whereas patients who did not
      experience clinical improvement showed an increased frequency of perforin
      expression. Our data suggest that fluctuations in these cell subsets are
      associated with both the immunomodulatory effect of IFN-alpha and the observed
      clinical benefit of IFN-alpha treatment in patients with HAM/TSP.

PMID- 14702151
TI  - Prediagnostic human T lymphotropic virus type I provirus loads were highest in
      Jamaican children who developed seborrheic dermatitis and severe anemia.
AB  - In a recent clinical analysis of 308 Jamaican children, human T lymphotropic
      virus type I (HTLV-I) infection was found to be associated with significantly
      higher incidence rates of seborrheic dermatitis, eczema, and persistent
      hyperreflexia of the lower limbs and with nonsignificantly increased rates of
      severe anemia and abnormal lymphocytes. Results of examination of HTLV-I viral
      markers in the 28 HTLV-I-infected children provided virologic support for the
      epidemiologic associations of HTLV-I with seborrheic dermatitis and severe anemia
      in childhood.

PMID- 14702152
TI  - Epidemiology of human papillomavirus infection and abnormal cytologic test
      results in an urban adolescent population.
AB  - We determined the prevalence of and the risk factors for human papillomavirus
      (HPV) infection and abnormal cytologic test results in 312 adolescent girls (mean
      age, 16.1 years). Subjects had a median of 2 years of sexual activity and 4
      lifetime sex partners. Cervical HPV was detected by use of L1-consensus
      polymerase chain reaction in 64% of subjects; half of those with HPV had >1 type,
      and 77% had >/=1 high-risk type. Independent risk factors for HPV were lifetime
      number of sex partners, age of partner, and douching. Cytologic abnormalities
      were common (20.9% of subjects had atypical squamous cells of uncertain
      significance, and 17.0% had high- or low-grade squamous intraepithelial lesions)
      and were significantly associated with detection of HPV (P=.0001); however, most
      (51.6%) subjects with HPV had normal cytologic test results.

PMID- 14702153
TI  - Incidence of resistance in a double-blind study comparing lopinavir/ritonavir
      plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine.
AB  - Study M98-863 was a double-blind, randomized, phase 3 study that compared
      lopinavir/ritonavir with nelfinavir, each coadministered with stavudine and
      lamivudine, in 653 antiretroviral therapy-naive human immunodeficiency virus
      (HIV) type 1-infected subjects. The incidence of HIV drug resistance was analyzed
      using baseline and rebound virus isolates from subjects with plasma HIV RNA >400
      copies/mL from weeks 24 to 108 of therapy. No evidence of genotypic or phenotypic
      resistance to lopinavir/ritonavir, defined as any active site or primary mutation
      in HIV protease, was detected in virus isolates from 51 lopinavir/ritonavir
      treated subjects with available genotypes. Primary mutations related to
      nelfinavir resistance (D30N and/or L90M) were observed in 43 (45%) of 96
      nelfinavir-treated subjects. Resistance to lamivudine and stavudine was also
      significantly higher in nelfinavir-treated versus lopinavir/ritonavir-treated
      subjects. These differences suggest substantially different genetic and
      pharmacological barriers to resistance for these 2 protease inhibitors and may
      have implications for strategies for initiating antiretroviral therapy.

PMID- 14702154
TI  - Pathogen-specific induction of CD154 is impaired in CD4+ T cells from human
      immunodeficiency virus-infected patients.
AB  - The pathogenesis of immunodeficiency associated with human immunodeficiency virus
      (HIV) infection remains incompletely understood. CD154, a molecule that is
      expressed primarily on activated CD4(+) T cells, is pivotal for regulation of
      cell-mediated and humoral immunity and is crucial for control of many
      opportunistic infections. We investigated whether CD4(+) T cells from HIV
      infected patients exhibit defective induction of CD154 in response to
      opportunistic pathogens. Incubation of purified human CD4(+) T cells with
      monocytes plus antigenic preparations of either Candida albicans,
      cytomegalovirus, or Toxoplasma gondii resulted in induction of CD154. Expression
      of CD154 in response to these pathogens was impaired in CD4(+) T cells from HIV
      infected patients. This defect correlated with decreased production of
      interleukin (IL)-12 and interferon (IFN)-gamma in response to T. gondii.
      Recombinant CD154 partially restored secretion of IL-12 and IFN-gamma in response
      to T. gondii in cells from HIV-infected patients. Together, defective induction
      of CD154 is likely to contribute to impaired cell-mediated immunity against
      opportunistic pathogens in HIV-infected patients.

PMID- 14702155
TI  - Potent cross-group neutralization of primary human immunodeficiency virus
      isolates with monoclonal antibodies--implications for acquired immunodeficiency
      syndrome vaccine.
AB  - Human immunodeficiency virus type 1 (HIV-1) is phylogenetically classified into
      groups and clades (or subtypes). Human neutralizing monoclonal antibodies
      (nMAbs), originally isolated from individuals infected with HIV-1 group M-clade
      B, neutralized not only primary HIV-1 clade B isolates in vitro but also primary
      isolates of other group M clades (A, C, D, E, and F). This corrected the
      previously held notion that primary HIV-1 isolates are resistant to neutralizing
      antibodies. Here we show that anti-HIV-1 group M-clade B nMAbs potently
      neutralized primary isolates of the phylogenetically distant HIV-1 group O. We
      and others have previously shown that passive immunization with human nMAbs
      protected adult or neonatal primates against infection with simian-human
      immunodeficiency virus strains encoding HIV-1 group M-clade B envelope genes. The
      in vitro cross-group neutralization shown here underscores the broad potential of
      these nMAbs against divergent virus variants and the relevance of their epitopes
      in the design of acquired immunodeficiency syndrome vaccines.

PMID- 14702156
TI  - Characterization of pathogenic Escherichia coli in human immunodeficiency virus
      related diarrhea in Senegal.
AB  - Stool samples obtained from 594 Senegalese patients were examined for
      characterization of pathogenic Escherichia coli in human immunodeficiency virus
      (HIV)-related diarrhea. Multiple virulence genes were observed in stool samples
      obtained from HIV-infected patients with diarrhea. Enteroaggregative E. coli and
      enteroinvasive E. coli were present in stool samples obtained from patients with
      diarrhea significantly more often than in stool samples obtained from patients
      without diarrhea (P=.000001). Quinolones may be an effective alternative
      treatment for E. coli-related diarrhea in HIV-infected adults in Senegal.

PMID- 14702157
TI  - Identification of new candidate vaccine antigens made by Streptococcus pyogenes:
      purification and characterization of 16 putative extracellular lipoproteins.
AB  - Putative extracellular lipoproteins made by group A Streptococcus (GAS) are the
      focus of this study, which was designed to identify new candidate vaccine
      antigens. Bioinformatic analysis of a serotype M1 GAS strain identified 30 open
      reading frames encoding putative lipoproteins. The genes encoding the mature form
      of 29 of these proteins were cloned, and 16 recombinant proteins were
      overexpressed in Escherichia coli and purified to apparent homogeneity. The genes
      encoding these 16 proteins were highly conserved in GAS strains for which genome
      sequence data are available (serotypes M1, M3, M5, M12, M18, and M28). Mice
      inoculated subcutaneously with GAS and humans with GAS pharyngitis and invasive
      infections seroconverted to most of the 16 recombinant proteins, which indicates
      that these lipoproteins were produced during infection. The blood of mice
      actively immunized with 5 of the 16 recombinant proteins had significantly
      (P<.05) increased growth-inhibitory activity, compared with the blood of
      unimmunized mice, which identified these proteins as potential new vaccine
      candidates.

PMID- 14702158
TI  - Expression of glycopeptide-resistance gene in response to vancomycin and
      teicoplanin in the cardiac vegetations of rabbits infected with VanB-type
      Enterococcus faecalis.
AB  - VanB-type resistance in enterococci corresponds to resistance to vancomycin but
      not to resistance to the related glycopeptide teicoplanin, because the vanB gene
      cluster is activated by the VanR(B)-VanS(B) 2-component regulatory system in
      response to vancomycin but not to teicoplanin. Mutations in the vanS(B) gene
      allow for constitutive or teicoplanin-inducible expression of the resistance
      genes. To analyze in vivo expression of the van genes in rabbits with
      experimental endocarditis, a VanB-type Enterococcus faecalis with a
      transcriptional fusion between the P(YB) promoter of resistance genes and the
      gfpmut1 gene for the green-fluorescent protein in the chromosome was constructed.
      Rounded heaps containing fluorescent bacteria were detected in vegetation slides
      from rabbits treated with vancomycin but not in those from control rabbits,
      revealing induction of a tightly regulated vanB gene cluster. Teicoplanin
      resistant mutants were detected as fluorescent bacteria in rabbits treated with
      teicoplanin. Thus, the reporter system monitored expression of a glycopeptide
      resistance gene in vivo at a single-cell level.

PMID- 14702159
TI  - Hospital water as a source of Mycobacterium avium complex isolates in respiratory
      specimens.
AB  - The clinical significance of recovery of Mycobacterium avium complex (MAC)
      organisms from respiratory specimens is poorly understood. One hundred sixty-one
      respiratory MAC isolates from 131 patients at Grady Memorial Hospital (Atlanta)
      and 13 MAC isolates from the hospital's hot water system were examined. Of the
      131 patients, 35 (27%) had MAC disease, and 96 (73%) did not; 94 (72%) were human
      immunodeficiency virus infected. Ten different clusters were identified by pulsed
      field gel electrophoresis. Patients without MAC disease were significantly more
      likely to have clustered isolates than were patients with MAC disease. Of 110 MAC
      isolates recovered from patients without MAC disease, 72 (65%) were part of a
      single large cluster that contained isolates recovered from the hospital's hot
      water system; 13 (25%) of 51 isolates from patients with MAC disease were also in
      this cluster. We conclude that acquisition of MAC from institutional water
      systems leads to substantial MAC disease but that most patients with MAC
      recovered from respiratory specimens have only transient colonization by MAC.

PMID- 14702160
TI  - Mycobacterium tuberculosis defective in phthiocerol dimycocerosate translocation
      provides greater protective immunity against tuberculosis than the existing
      bacille Calmette-Guerin vaccine.
AB  - We demonstrate that Mycobacterium tuberculosis that is unable to export the
      complex lipid phthiocerol dimycocerosate has a decreased capacity to replicate in
      mice and affords sustained protective immunity against M. tuberculosis infection
      Protection was significantly better than that provided by the existing vaccine,
      Mycobacterium bovis bacille Calmette-Guerin (BCG), and this improved protective
      efficacy was maintained for at least 24 weeks after vaccination. Protection
      afforded by this attenuated strain coincided with a number of factors that were
      not associated with BCG vaccination: long-term persistence of the strain within
      the host, sustained and potent induction of antimycobacterial interferon-gamma
      secreting cells equal to that induced by virulent M. tuberculosis, and
      elicitation of T cells recognizing dominant M. tuberculosis antigens absent from
      BCG. These results suggest that the BCG vaccine may be too attenuated to afford
      effective protective immunity against tuberculosis, and vaccine strains that can
      provide sustained delivery of mycobacterial antigens are promising
      antituberculosis vaccine candidates.

PMID- 14702161
TI  - Selective induction of matrix metalloproteinases by Borrelia burgdorferi via toll
      like receptor 2 in monocytes.
AB  - Regulation of secretion of matrix metalloproteinase (MMP) underlies the basis of
      numerous physiological and pathological processes in multicellular organisms. The
      Toll receptor family, which is conserved from Drosophila species to humans,
      mediates pattern recognition of a diversity of ligands involved in morphogenesis
      and innate immunity. Here, we show that secretion of MMP-9 is selectively induced
      through Toll-like receptor (TLR) 2 in human and murine monocytic cells stimulated
      with Borrelia burgdorferi. Secretion of MMP-1 was shown to be stimulated through
      a pathway other than TLR2, under identical conditions. Analysis of nuclear
      extracts indicated that activator protein (AP)-1 was reduced in TLR2-neutralized
      monocytic cells, suggesting that AP-1 plays a role in the transcriptional
      activation of MMP-9 through TLR2. The specific induction of MMP-9 through TLR2
      provides direct evidence of a new role for this ancient receptor family in
      regulating secretion of MMPs and demonstrates evolutionary convergence between
      invertebrate morphogenesis and the vertebrate innate immune system.

PMID- 14702162
TI  - Most of the response elicited against Wolbachia surface protein in filarial
      nematode infection is due to the infective larval stage.
AB  - Immune responses to the intracellular Wolbachia bacteria of filarial nematodes
      are thought to contribute to the pathologic process of filarial infection. Here,
      we compare antibody responses of subjects living in an area where lymphatic
      filariasis is endemic with antibody responses elicited in a murine model of
      filarial infection, to provide evidence that the infective larval stage (L3), not
      adult nematodes, are the primary inducer of responses against Wolbachia. In human
      subjects, antibody responses to Brugia malayi Wolbachia surface protein (WSP) are
      most often correlated with antibody responses to the L3 stage of B. malayi.
      Analysis of anti-WSP responses induced in mice by different stages of the rodent
      filariae Litomosoides sigmodontis shows that the strongest anti-WSP response is
      elicited by the L3 stage. Although adult filarial nematode death may play a role
      in the generation of an anti-WSP response, it is the L3 stage that is the major
      source of immunogenic material, and incoming L3 provide a continual boosting of
      the anti-WSP response. Significant exposure to the endosymbiotic bacteria may
      occur earlier in nematode infection than previously thought, and the level of
      exposure to infective insect bites may be a key determinant of disease
      progression.

PMID- 14702163
TI  - Studies in pneumonia and pneumococcus infection. 1904.

PMID- 14702164
TI  - Distributional map of the terminal and sub-terminal sugar residues of the
      glycoconjugates in the prepubertal and postpubertal testis of a subject affected
      by complete androgen insensitivity syndrome (Morris's syndrome): lectin
      histochemical study.
AB  - In the present research we have investigated the distribution of the sugar
      residues of the glycoconjugates in the prepubertal and postpubertal testes of a
      subject with Morris's syndrome (CAIS, Complete Androgen Insensitivity Syndrome).
      For this purpose a battery of six horseradish peroxidase-conjugated lectins was
      used (SBA, PNA, WGA, ConA, LTA and UEAI). We have obtained a complete
      distributional map of the terminal and sub-terminal oligosaccharides in the
      tunica albuginea, interstitial tissue, lamina propria of the seminiferous
      tubules, Leydig cells, Sertoli cells, spermatogonia, mastocytes and endothelial
      cells. Furthermore the present study has shown that a large amount of sugar
      residues were detectable in the prepubertal and postpubertal testes but that some
      differences exist with particular regard to the Sertoli cells. The Sertoli cells
      and the Leydig cells of the retained prepubertal testis of the patient affected
      by Morris's syndrome were characterized by the presence of alpha-L-fucose, which
      was absent in the retained prepubertal testis of the normal subjects. Comparing
      the results on the postpubertal testis with those obtained on the same aged
      testis of healthy subjects we have demonstrated that alpha-L-fucose in the
      Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the Leydig
      cells are a unique feature of the subject affected by Morris's syndrome. D
      galactose (ss1,3)-N-acetyl-D-galactosamine and sialic acid, which are present in
      the Leydig cells of the normal testis were never observed in the same cells of
      the postpubertal testis of the CAIS patient.

PMID- 14702165
TI  - Expression and significance of cell immunohistochemical markers (HHF-35, CD-31,
      Bcl-2, P-53 and apopDETEC) in hypertrophic cardiomyopathy.
AB  - There are several hypotheses concerning the pathogenesis of hypertrophic
      cardiomyopathy (genetic, ischaemic, immune, inflammatory and apoptosis
      induction). We have studied three types of cardiomyopathy in order to observe the
      expression and assess the significance of different immunohistochemical markers
      (muscular actin, CD-31, proliferation cell nuclear antigen -PCNA-, Ki-67, and
      markers related with programmed cell death, bcl-2, p-53 and apopDETEC). We
      studied different microscopic (haematoxylin-eosin and Masson's thrichrome) and
      immunohistochemical parameters (streptavidin-biotin-peroxidase and "in situ"
      hybridisation) of forty cases: ten each of hypertensive hypertrophic
      cardiomyopathy, essential hypertrophic cardiomyopathy, hypertrophic
      cardiomyopathy in patients treated with chemotherapy and morphologically "normal"
      hearts. Our findings point to an absence of structural marker expression (actin
      and CD-31) in cases of hypoxic damage. The distribution and intensity of
      apoptosis markers, a seen by "in situ" hybridisation were irregular, and the rest
      of the markers studied showed negative results, with the exception of acridin
      orange (a marker of hypoxic damage). In our opinion, the above
      immunohistochemical markers, especially actin and CD-31, could be used for
      differentiating hypoxic lesions in these three types of cardiomyopathy. Moreover,
      it is difficult to know the significance of the apoptosis markers, because the
      autolysis process produces cross reactions with false positive results. We think
      that there is a need for new studies on DNA breakdown processes during the post
      mortem interval. To avoid autolysis problems the post-mortem material needs to be
      as fresh as possible.

PMID- 14702166
TI  - Pathological change of articular cartilage in the mandibular head treated with
      immunosuppressant FK 506.
AB  - While several reports have documented immunosuppressant-induced osteoporosis, the
      exact mechanism of the pathological change of the joint remains to be clarified.
      In the present study, we have demonstrated the pathological change of the
      articular cartilage in the mandibular head of five Sprague-Dawley rats
      administered with the immunosuppressant FK 506 for 28 days. Three-dimensional
      micro-computed tomography of the mandibular heads in treated rats showed a
      significant decrease in trabecular bone volume compared to control rats.
      Histological observation revealed atrophic change of the articular cartilage.
      Immunohistological observation using anti-proliferative cell nuclear antibody
      (PCNA), type I, II, and type X collagen antibodies showed significantly decreased
      proliferation and differentiation of chondrocytes in the articular cartilage
      compared with the control group (p<0.05). Tartrate-resistant acid phosphatase
      (TRAP) staining revealed no significant difference in the numbers of osteoclasts
      at the chondro-osseous junction. Thus, FK 506 administration inhibited
      chondrogenic cell proliferation and differentiation and might cause osteoporotic
      change of subcartilage trabecular bone that subsequently forms in the mandibular
      head.

PMID- 14702167
TI  - Immunohistochemical identification of intracytoplasmic lumens by cytokeratin
      typing may differentiate renal oncocytomas from chromophobe renal cell
      carcinomas.
AB  - Renal oncocytomas and chromophobe renal cell carcinomas (RCCs) share a common
      phenotype and both originate from the intercalated cells of the collecting duct.
      This makes it very difficult to differentiate between the two tumors
      immunohistochemically. Therefore, we studied the results of immunohistochemistry
      focusing on certain characteristic structures that are occasionally present in
      renal oncocytomas. We carried out Hale's colloidal iron staining and
      immunohistochemistry for various cytokeratins (cytokeratins 7, 8, 10, 10/13, 14,
      18, 19 and 20, and AE1/AE3) in four oncocytomas and six chromophobe RCCs. In
      addition, one renal oncocytoma and one chromophobe RCC were studied using
      electron microscopy. Two renal oncocytomas and one chromophobe RCC were
      completely unstained by colloidal iron. There was no evident difference between
      the immunohistochemical characteristics of oncocytomas and those of chromophobe
      RCCs. However, in all four renal oncocytomas we identified intracytoplasmic ring
      like positive reactions for some cytokeratins (at least 3 antigens of
      cytokeratins 7, 8 and 19, and AE1/AE3), which corresponded ultrastructurally to
      the intracytoplasmic lumens (ICLs). In contrast, no such structures were found in
      any of the chromophobe RCCs using the antibodies employed. Therefore,
      immunohistochemical identification of ICLs by cytokeratin typing may be useful
      for differentiating between renal oncocytomas and chromophobe RCCs and be more
      sensitive in this respect than colloidal iron staining.

PMID- 14702168
TI  - Immunohistochemical study of the upper surface layer in rat mandibular condylar
      cartilage.
AB  - Both hyaluronic acid and fibronectin localizations were examined in the upper
      surface layer of rat mandibular condylar cartilages by immunohistochemical
      techniques. Their delicate structure was successfully preserved by preparation
      procedures of joint condyles with disks. Paraformaldehyde-fixed cartilaginous
      tissues were cut in a cryostat, and cryosections were analyzed using streptavidin
      peroxidase and indirect immunofluorescence methods. Another immunogold method
      with conventional preparation procedures and a quick-freezing method was
      performed for their ultrastructural analyses. Both hyaluronic acid-binding
      protein and anti-fibronectin antibody were used to localize hyaluronic acid and
      fibronectin in the mandibular condylar cartilage, respectively. Some cryosections
      were pre-treated with hyaluronidase and chondroitinase before such labeling. The
      upper surface layer was composed of double laminar structures. One bordered with
      the cartilage matriceal surface, which was positive for fibronectin. The
      hyaluronic acid was localized over the fibronectin layer. Therefore, the
      hyaluronic acid in vivo was bound with fibronectin in the cartilaginous matrix,
      performing lubrication for the mandibular joint movement.

PMID- 14702169
TI  - Expression of vascular endothelial growth factor (VEGF) and association with
      microvessel density in small-cell and non-small-cell lung carcinomas.
AB  - Recent studies have demonstrated that tumor angiogenesis is a prognostic factor
      for various malignant neoplasms. Specifically, in non-small-cell lung carcinomas
      (NSCLCs) most reports show an association between neovascularization and vascular
      endothelial growth factor (VEGF) expression as well as the presence of metastases
      and survival, although a few reports do not agree with these findings.
      Angiogenesis is not clearly characterized in small-cell lung carcinomas (SCLCs),
      since they are rarely treated by surgery, and thus the available tissue for
      biological characterization is sparse. The aim of the present study was to
      investigate angiogenesis and the expression of VEGF in lung tumors. We examined
      88 non-small-cell and 39 small-cell lung carcinomas. Angiogenesis was estimated
      by determining microvessel counts, with the use of anti-CD31 and anti-factor VIII
      antibodies and expression of VEGF was also evaluated immunohistochemically. Our
      data showed that in NSCLCs angiogenesis was more prominent in poorly
      differentiated neoplasms and correlated with VEGF expression, therefore it is at
      least in part mediated by the latter. Interestingly, in SCLCs a higher
      vascularization was noted. However, there was no strong association with VEGF
      expression. Thus, small-cell lung carcinoma may represent a suitable neoplasm for
      testing antiangiogenic drugs in combination with chemotherapy. Nevertheless,
      antiangiogenic therapy should not be targeted specifically to the VEGF pathway,
      since in SCLCs other mediators of angiogenesis may be important as well.

PMID- 14702170
TI  - The effects of low laser irradiation on angiogenesis in injured rat tibiae.
AB  - The influence of He-Ne laser radiation on the formation of new blood vessels in
      the bone marrow compartment of a regenerating area of the mid-cortical diaphysis
      of the tibiae of young adult rats was studied. A small hole was surgically made
      with a dentistry burr in the tibia and the injured area received a daily laser
      therapy over 7 or 14 days transcutaneously starting 24 h from surgery. Incident
      energy density dosages of 31.5 and 94.5 Jcm(-2) were applied during the period of
      the tibia wound healing investigated. Light microscopic examination of
      histological sections of the injured area and quantification of the newly-formed
      blood vessels were undertaken. Low-level energy treatment accelerated the
      deposition of bone matrix and histological characteristics compatible with an
      active recovery of the injured tissue. He-Ne laser therapy significantly
      increased the number of blood vessels after 7 days irradiation at an energy
      density of 94.5 Jcm(-2), but significantly decreased the number of vessels in the
      14-day irradiated tibiae, independent of the dosage. These effects were
      attributed to laser treatment, since no significant increase in blood vessel
      number was detected between 8 and 15 non-irradiated control tibiae. Molecular
      mechanisms involved in low-level laser therapy of angiogenesis in post-traumatic
      bone regeneration needs further investigation.

PMID- 14702171
TI  - Structural patterns of swine ileal mucosa following L-glutamine and nucleotide
      administration during the weaning period. An histochemical and histometrical
      study.
AB  - Dietary supplementations with L-glutamine and/or nucleotides were screened for
      their effects on intestinal mucosa in 16 female weaning piglets. The animals were
      transported to the university's facilities 24 hours after weaning. They were
      grouped four to a pen in controlled environmental conditions and fed one of the
      following four diets for 28 days: control diet (C); C+0.5% L-glutamine (G);
      C+0.05% "nucleotides" (N); and C+0.5 % L-glutamine+0.05% "nucleotides" (GN).
      Individual body weights and feed intake per group were recorded at the beginning
      and the end of the study as well as weekly during it. There were no significant
      performance differences among the groups. After 28 days the animals were
      slaughtered and the distal ileum and liver were examined histologically. Anti
      proliferating cell nuclear antigen (PCNA) as well as anti-human macrophage
      immunostaining, and a modified TdT-mediated dUTP nick-end labeling technique
      (TUNEL) were performed, and intraepithelial lymphocyte percentage was evaluated
      to assess morpho-functional aspects of the ileum. Histometry was performed by
      assessing cell indices and counts of immuno-reactive structures. Feeding G and/or
      N resulted in an increase in villi (V) height, crypt (C) depth, and a decrease in
      V:C ratio (P<0.01). In addition, feeding G and/or N resulted in an increase in
      mitotic mucosal cells (M), and a decrease in apoptotic mucosal cells (A), thus
      decreasing the A:M index (P<0.01). The percentages of mucosal macrophages were
      greater in G and/or N groups (P<0.001) than in control piglets, and similarly
      among the groups the percentages of intraepithelial lymphocytes varied (P<0.01).
      Our data showed that the diet supplementation with G and/or N had positive
      effects on some morpho-functional characteristics of piglet ileal mucosa. These
      ameliorative effects may potentially be linked to a good responsiveness of
      piglets to a stressful period, like a precocious weaning is in this species.

PMID- 14702172
TI  - The distribution and role of myofibroblasts and CD34-positive stromal cells in
      normal pancreas and various pancreatic lesions.
AB  - To elucidate the distribution and role of myofibroblasts and CD34-positive
      stromal cells in various pancreatic lesions, we performed an immunohistochemical
      study using a streptoavidin-biotin immunoperoxidase technique. We selected 43
      pancreatic lesions from 1 biopsied, 22 surgically resected and 12 autopsied
      specimens: acute pancreatitis (n=3), chronic non-obstructive pancreatitis (n=4),
      obstructive pancreatitis (n=7), islet cell tumor (n=4), serous cystadenoma (n=7),
      mucinous cystadenoma (n=6), and invasive ductal carcinoma (n=12). In normal
      pancreas, myofibroblasts and CD34-positive stromal cells were predominantly
      present in the peridcutal and periacinar areas, respectively. Both myofibroblasts
      and CD34-positive cells were observed in the stroma of chronic pancreatitis. In
      four islet cell tumors, myofibroblasts were present in the stroma of the tumor
      center, but no CD34-positive stromal cells were identified. Additionally,
      myofibroblasts and CD34-positive stromal cells were located in the inner layer
      and the outer layer of the capsule of three islet cell tumors, respectively. In
      nine of the thirteen cystadenomas, only myofibroblasts were recognized in the
      cyst wall. In the remaining four cystadenomas, a small number of CD34-positive
      cells were observed in the cyst wall. In 12 invasive ductal carcinomas, the
      stroma possessed a lot of myofibroblasts, but there were no or few CD34-positive
      stromal cells. In conclusion, it seems that the abundant amount of CD34-stromal
      cells in the main lesions is characteristic of chronic inflammatory lesions.
      Myofibroblasts and CD34-positive stromal cells may play a role in regulating the
      tumor growth in the capsule of islet cell tumors of the pancreas.

PMID- 14702173
TI  - Morphological characterization of renal cell lines (BGM and VERO) exposed to low
      doses of lead nitrate.
AB  - The response to lead nitrate has been assessed in two cell lines of renal origin.
      The range of toxic concentrations was determined by Neutral Red assay after 24-h
      of exposure. Morphological changes in the Buffalo Green Monkey (BGM) and VERO
      cell lines after exposure to subcytotoxic doses (1.38 mM and 1.04 mM,
      respectively) equivalent to EC10 (effective concentrations 10%) of lead nitrate
      were evaluated at the ultrastructural level by transmission microscopy. The most
      notable finding in treated cells was the presence of inclusion bodies in the form
      of irregular granules of varying size in both cytoplasm and lysosomes. Cell
      membrane integrity was not affected. The number of phagolysosomes and myeline
      figures associated to the inclusion bodies was higher than in the control
      cultures. We conclude that the phagolysosomic mechanism fails to digest this
      metal ion and the BGM and VERO renal cell lines can be considered as useful tools
      for toxicological studies involving lead nitrate.

PMID- 14702174
TI  - Apoptosis of thymocytes in experimental African Swine Fever virus infection.
AB  - This paper report on the lesions occurred in the thymus in experimental acute
      African swine fever (ASF). Twenty-one pigs were inoculated with the highly
      virulent ASF virus (ASFV) isolate Spain-70. Animals were slaughtered from 1 to 7
      days post infection (dpi). Three animals with similar features were used as
      controls. Thymus samples were fixed in 10% buffered formalin solution for
      histological and immunohistochemical study and in 2.5% glutaraldehyde for
      ultrastructural examination. For immunohistochemical study, the avidin-biotin
      peroxidase complex (ABC) technique was used to demonstrate viral protein 73 and
      porcine myeloid-histiocyte antigen SWC3 using specific monoclonal antibodies.
      Cell apoptosis was evaluated by the TUNEL assay. Blood samples were taken daily
      from all pigs and were used for leukocyte counts. The results of this study show
      a severe thymocyte apoptosis not related to the direct action of ASFV on these
      cells, but probably to a quantitative increase in macrophages in the thymus and
      their activation. A decrease in the percentage of blood lymphocytes was observed
      at the same time No significant vascular changes were observed in the study. With
      these results we suggest that ASFV infection of the thymus does not seem to play
      a critical role in the acute disease. Although severe apoptosis was observed,
      animals died because of the severe lesions found in the other organs.

PMID- 14702175
TI  - Skeletal muscle regeneration and Trypanosoma cruzi-induced myositis in rats.
AB  - Although Chagas' disease is known to provoke severe acute myositis, information
      on muscle regeneration is missing. The current paper shows that during T. cruzi
      infection in rats, skeletal muscle parasitism and the consequent inflammatory
      process are higher in muscle with a high proportion of type-I myofibres (soleus
      and diaphragm). Immunohistochemistry showed an acute inflammatory process
      characterized by ED1+ and ED2+ macrophages, CD8+ lymphocytes, and NK cells.
      Parasite-nest rupture provoked segmental degeneration of myofibres followed by
      regeneration. These phenomena were observed at both light and transmission
      electron microscopy levels. Myofibre regeneration involved activation of
      satellite cells assessed by the expression of MyoD, a muscle-specific
      transcription factor. Ultrastructural evidence of fusion of myoblast-like cells
      with the intact segment of degenerating fibres has been provided. At the chronic
      phase no signs of fibrosis were found, but sparse and small inflammatory foci
      were found. Our results argue against the relevant participation of autoimmunity
      phenomena in both acute and chronic phases and furnish a new view for explaining
      histopathological findings in human patient muscles.

PMID- 14702176
TI  - Overexpression of iNOS and down-regulation of BMPs-2, 4 and 7 in retinoic acid
      induced cleft palate formation.
AB  - The present work studied the induction of cleft palate formation in embryos
      developed from pregnant BALB/c mice treated orally with retinoic acid (RA).
      Previous studies on mature somatic cell types showed that RA exerted inhibitory
      effects on inducible nitric oxide synthase (iNOS) production. For the first time,
      our study has shown that RA actually stimulates significant expression of iNOS at
      specific zones of the affected embryonic palatal tissues at three consecutive
      stages, from gestation day 13 (GD13) to day 16 (GD16). Enzymatically, iNOS
      facilitates intracellular nitric oxide (NO) synthesis from L-arginine. When NO
      reacts with reactive superoxides it may result in irreparable cell injury. NO was
      also reported to induce apoptosis in some mammalian cell systems. Based on our
      findings, we propose that such an increase in NO production might be associated
      with apoptosis in the embryonic palatal tissues in the RA-treated mice. The
      detrimental effects of NO resulted in a reduction in proliferating palatal cells
      and therefore disturbed the normal plasticity of the palatal shelves. With iNOS
      overexpression, our findings also showed that there was significant concomitant
      down-regulation in the expressions of Bone Morphogenetic Proteins (BMPs) -2, 4,
      and 7 with regional variations particularly in the palatal mesenchymal cells for
      those embryos developing cleft palate. Since specific spatial and temporal
      expressions of BMPs -2, 4, and 7 are critical during normal palatal
      morphogenesis, any deficiency in the epithelial-mesenchymal interaction may
      result in retarding growth at the embryonic palatal shelves. Taken together, our
      study has demonstrated cleft palate formation in the BALB/c embryos involved
      overexpression of iNOS and down-regulation of BMPs-2, 4 and 7.

PMID- 14702177
TI  - Interleukin-1beta-induced expression of the urokinase-type plasminogen activator
      receptor and its co-localization with MMPs in human articular chondrocytes.
AB  - The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in
      cartilage degradation during osteoarthritis as it regulates pericellular
      proteolysis mediated by serine proteinases. Another important family of
      proteinases responsible for ECM destruction in arthritis are the matrix
      metalloproteinases (MMPs). MMPs are regulated by IL-1beta, a cytokine that plays
      a pivotal role in pathogenesis of osteoarthritis. This study was undertaken to
      address two questions: 1. Is uPAR-expression regulated by proinflammatory
      cytokines such as IL-1beta? 2. Does a functional co-localization exist between
      uPAR and MMPs? By immunohistochemical analysis we observed enhanced expression of
      uPAR on chondrocytes derived from osteoarthritic human cartilage compared to non
      osteoarthritic controls. We found an IL-1beta-mediated expression of uPAR by
      immunoelectron microscopy. Western blot analysis demonstrated that IL-1beta
      stimulated expression of uPAR on chondrocytes in vitro increased in a dose
      dependent manner. Furthermore, we found a functional co-localization between uPAR
      and MMP-9 on IL-1beta-stimulated chondrocytes by means of a co
      immunoprecipitation assay. Expression of uPAR in osteoarthritic cartilage but not
      in healthy cartilage suggests that uPAR plays a role in cartilage breakdown. We
      propose that uPAR-mediated effects e.g. pericellular proteolysis are one of other
      cytokine (IL-1beta)-mediated events that contribute to the pathogenesis of
      osteoarthritis. Furthermore, we found that MMPs and uPAR were part of the same
      cell surface complexes in chondrocytes. This finding underlines a functional
      interaction between MMPs and the serine proteinase system in the fine regulation
      of pericellular proteolysis. Interfering with uPAR signaling may present a novel
      target in arthritis therapy to prevent excessive proteolytic degradation.

PMID- 14702178
TI  - Syncytial giant cell component. Review of 55 renal cell carcinomas.
AB  - Different types of multinucleated giant cells (MGC) have been documented in
      tumors with osteoclast-like appearance, with trophoblastic differentiation or as
      tumoral malignant giant cells. A new variety of MGC has been described in renal
      cell carcinoma. In order to study the frequency, nature and significance of this
      cellular type, we have reviewed our files. To assess the presence, nature and
      significance of these MGC in renal cell carcinomas and associated histologic
      subtype. To review all malignant renal tumors diagnosed in the last 5 years in
      our hospital and to carry out a morphologic and immunohistochemical study in
      renal cell carcinomas with syncytial type MGC. 55 renal cell carcinomas were
      reviewed. Clear cell (conventional) renal cell carcinoma was the most common type
      encountered (40 cases); two of these cases showed syncytial type MGC and low
      grade malignancy. Microscopically the MGC contained from 5 to 40 nuclei.
      Immunohistochemically, mononucleated and multinucleated cells were positive for
      cytokeratin CAM 5.2, cytokeratin AE1/AE3 and weakly positive for vimentin.
      Histiocytic, muscular, neural markers, beta-HCG and alpha-fetoprotein were
      negative. The presence of syncytial type MGC in renal cell carcinomas is an
      exceptional event. Among 55 renal cell carcinomas we found two cases, both of
      which were of clear cell subtype and low grade malignancy. The MGC proved
      positive for epithelial markers and probably are the result of mononucleated
      tumoral cell fusion. We are unaware of the impact of this MGC in the outcome of
      patients; such cells appear in low grade carcinomas and do not seem to be of
      dismal prognosis.

PMID- 14702179
TI  - HSP 27 as possible prognostic factor in patients with oral squamous cell
      carcinoma.
AB  - HSP27 belongs to the Heat shock protein (HSP) family, which plays essential
      functions in cells under physiological conditions and prevents stress-induced
      cellular damage. The aim of this study was to investigate the biological role of
      HSP27 in oral tumorigenesis. MATERIALS AND METHODS: Seventy-nine cases of oral
      squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27
      expression by immunohistochemistry. Moreover, the western blot analysis was
      performed on two cases of normal mucosa and five cases of OSCC. RESULTS: Normal
      oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC
      (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead
      a decrease in staining, which was diffuse, homogeneous, or with alternation of
      positive and negative areas in a single tumor ("mosaic" pattern). Only 7 cases of
      OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node
      metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced
      (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II
      had a higher score than stages III and IV (stage I > stage II > stage III > stage
      IV). There was also a statistically significant correlation between HSP27
      expression and grade: HSP27 expression was reduced in poorly differentiated
      tumours (P < 0.05). When analysed for prognostic significance, patients with
      negative/reduced HSP27 expression had poorer survival rates than the group with
      positive HSP27 expression (P < 0.05). The statistical analysis of these findings
      showed no significant correlation between HSP27 expression, sex, and tumour size.
      CONCLUSION: Cases with reduced expression were more aggressive and poorly
      differentiated. These data suggest that HSP27 expression may be useful in order
      to identify cases of oral squamous cell carcinoma with more aggressive and
      invasive phenotype providing novel diagnostic and prognostic information on
      individual patient survival with oral cancers.

PMID- 14702180
TI  - The prognostic significance of thymidine phosphorylase, thymidylate synthase and
      dihydropyrimidine dehydrogenase mRNA expressions in breast carcinomas.
AB  - Thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine
      dehydrogenase (DPD) have been indicated as possible predictive markers for
      epithelial malignancies. All these three enzymes are actively involved in 5-FU
      metabolism. In this report, we investigated mRNA expression of these factors with
      real-time quantitative PCR in a series of 86 micro-selected breast carcinomas and
      8 micro-selected tumour-adjacent normal breast epithelial specimens. Highly
      variable mRNA expressions of these factors were observed in both normal and
      cancerous samples. TP and TS mRNA expressions in breast carcinomas were elevated,
      but only TS mRNA expression showed a trend for statistical difference, compared
      with the expression in normal breast epithelial samples. Although the DPD mRNA
      expression range in tumours was also elevated, the average mean was reduced in
      tumours compared to that in normal samples. No association between mRNA
      expressions of TP, TS and DPD and clinicopathological features such as
      histological grade, tumour size, node status, S-phase fraction, ploidy, and
      clinical stage was found. A negative association between DPD mRNA expression and
      age was, however, revealed. Ten-year follow-up analysis showed no association
      between TP and DPD mRNA expression and clinical outcome. An high level of TS mRNA
      expression, however, was associated with a shorter clinical survival, indicating
      its potential role as a clinical marker in breast carcinoma.

PMID- 14702181
TI  - Time of origin of the rat pineal gland cells. A bromodeoxyuridine
      immunohistochemical study.
AB  - The immunohistochemical detection of bromodeoxyuridine (BrdU) was used to study
      the time of origin of the cells in the pineal gland of the rat. A study was made
      involving 17 groups of 4 rats each, administered with a single dose of
      bromodeoxyuridine (BrdU, 25 mg/kg) in 7 phases of the embryonic period (E15 to
      E21) and in 10 postnatal phases (between P0 and P30), followed by determination
      in each rat of the number of visible immune-labeled cells in the pineal gland 60
      days after birth. The results show that approximately 60% of the pineal cells
      underwent the last division(s) prior to differentiation in the prenatal period
      between E18 and E21. The rest of the pineal cells originated after birth,
      particularly in the first 5 postnatal days.

PMID- 14702182
TI  - The retinal pigment epithelium of the teleost Notopterus notopterus (Pallas):
      appearance of basal infoldings during prolonged dark-adaptation.
AB  - In teleosts, the basal part of the retinal pigment epithelium (RPE) is relatively
      smooth, i. e., it is free of basal membrane infoldings. In the featherback,
      Notopterus notopterus, whereas this is the situation in light adaptation, during
      dark-adaptation, especially when kept for prolonged periods (6-9 hour), numerous
      infoldings appear at the basal region, as found uniquely by transmission electron
      microscopy. In this teleost, during retinomotor movements, the rods move
      vitreally during dark-adaptation, while the cones do not elongate, and remain
      stationary in both light- and dark-adaptation. The significance of the appearance
      of basal infoldings in dark-adapted RPE is explained in terms of the pattern of
      retinomotor responses and the features of RPE and photoreceptors in this species.
      It is suggested that (1) the thick, impervious tapetal layer present in the RPE,
      (2) the unusual position of the photoreceptors in the visual cell layer of dark
      adapted retina, and (3) the presumably high demand for glucose and O2 of the
      outer retina during dark-adaptation might contribute to cause this phenomenon in
      this species. The available evidence tend to associate this phenomenon with the
      involvement of the RPE in nutrient and O2 delivery to the photoreceptors via the
      basal infoldings of the RPE in dark-adapted state in this species. This has not
      been reported for any other teleosts to date.

PMID- 14702183
TI  - Plasticity and regulation of human bone marrow stromal osteoprogenitor cells:
      potential implication in the treatment of age-related bone loss.
AB  - Human bone marrow stroma contains pluripotent mesenchymal progenitor cells that
      can give rise to many mesenchymal lineages, including chondroblasts, adipocytes
      or osteoblasts. The differentiation of these cells towards a specific lineage is
      dependent on hormonal and local factors activating specific transcription
      factors. Attempts have been recently made to identify osteoprogenitor cells in
      the human bone marrow and to identify the molecular mechanisms responsible for
      lineage-specific differentiation of human bone marrow stromal cells. Using a
      clonal pluripotent human bone marrow stromal cell line with tri-potential
      characteristics, we have provided evidence for a controlled reciprocal regulation
      of osteoblast/chondroblast and osteoblast/adipocyte differentiation of human bone
      marrow stromal cells. We have also shown that administration of TGFss that
      regulates the expression of specific osteoblast and adipocyte transcription
      factors can promote osteoblast differentiation and inhibit adipocyte conversion
      of rat marrow stromal cells in vivo. This indicates that the reciprocal
      relationship between osteoblastogenesis and adipogenesis can be manipulated in
      vivo in order to improve bone formation. Future studies will have to identify key
      signals for lineage-specific differentiation of human marrow stromal cells. This
      may result in the development of therapeutic strategies to promote the
      differentiation of these cells towards the osteoblast lineage and to inhibit
      excessive bone marrow adipogenesis associated with aging.

PMID- 14702184
TI  - Lung hysteresis: a morphological view.
AB  - The lung is an imperfect elastic body and for this reason dissipates energy. The
      energy applied to the lung in inspiration is not recovered in expiration. The
      property of dissipating energy receives the name of hysteresis. Lung hysteresis
      can be quantified because it applies to the area between the ascending and
      descending portions of the pressure-volume curve. Lung hysteresis comprises
      parenchymal hysteresis and bronchial hysteresis. Each point on the pressure
      volume applies to a different morphology of the lung parenchyma. The changes that
      take place in the lung architecture during expiration are related to alveolar
      recruitment: in inspiration the lung volume increases by the opening of distal
      air units. In expiration the lung volume decreases due to derecruitment. The
      energy is dissipated mainly in the alveolar recruitment process, in which forces
      of molecular adhesion, such as surface tension, are at work. Bronchial hysteresis
      involves the dead space and the bronchial wall being greater in expiration.

PMID- 14702185
TI  - Angiogenic factors and the endometrium following long term progestin only
      contraception.
AB  - Endometria from long term progestin only contraceptive-treated patients display
      abnormally enlarged blood vessels that are prone to bleeding as well as
      inflammation and possibly local diminution in blood flow. Such bleeding is also
      characterized by focal reductions in the expression of angiopoietin-1, a vessel
      stabilization and maturation agent, and excess production of the potent
      angiogenic agents, vascular endothelial growth factor and angiopoietin-2. In
      addition, tissue factor, the key initiator of hemostasis may play an angiogenic
      role either directly or via the activation of thrombin. This review article
      summarizes current findings related to the endometrial dysregulation of
      angiogenic/hemostatic agents following treatment with long term progestin only
      contraception. Studies in this area offer a promising avenue to alleviate
      abnormal uterine bleeding associated with this otherwise highly effective form of
      contraception

PMID- 14702186
TI  - Transcription factors involved in development and progression of malignant
      melanoma.
AB  - Up to date many genes are known to be deregulated in tumor development and
      progression. Genes important in tumorigenesis belong to families such as
      proteases, kinases and receptors. However, an important family of proteins is
      rarely discussed: the mediators of transcriptional control, the transcription
      factors. Usually, changes in transcription factor expression or activity can lead
      to more than just one downstream modification, as transcription factors are
      higher, thinking in a hierarchical way of expression control. In this review we
      summarize the role of the transcription factors AP-1, AP-2alpha, CREB, CtBP, ETS
      1, HMGB1, LEF/TCF/beta-catenin, MITF, NFkappaB, PAX3, SKI, Snail and STAT in
      carcinogenesis focusing on melanoma development and progression.

PMID- 14702187
TI  - Recent advances in osteoclast biology and pathological bone resorption.
AB  - The osteoclast is a bone-degrading polykaryon. Recent studies have clarified the
      differentiation of this cell and the biochemical mechanisms it uses to resorb
      bone. The osteoclast derives from a monocyte/macrophage precursor. Osteoclast
      formation requires permissive concentrations of M-CSF and is driven by contact
      with mesenchymal cells in bone that bear the TNF-family ligand RANKL. Osteoclast
      precursors express RANK, and the interaction between RANKL and RANK (which is
      inhibited by OPG) is the major determinant of osteoclast formation. Hormones,
      such as PTH/PTHrP, glucocorticoids and 1,25(OH)2D3, and humoral factors,
      including TNFalpha, interleukin-1, TGFss and prostaglandins, influence osteoclast
      formation by altering expression of these molecular factors. TNFalpha, IL-6 and
      IL-11 have also been shown to promote osteoclast formation by RANKL-independent
      processes. RANKL-dependent/independent osteoclast formation is likely to play an
      important role in conditions where there is pathological bone resorption such as
      inflammatory arthritis and malignant bone resorption. Osteoclast functional
      defects cause sclerotic bone disorders, many of which have recently been
      identified as specific genetic defects. Osteoclasts express specialized proteins
      including a vacuolar-type H+-ATPase that drives HCl secretion for dissolution of
      bone mineral. One v-ATPase component, the 116 kD V0 subunit, has several
      isoforms. Only one isoform, TCIRG1, is up-regulated in osteoclasts. Defects in
      TCIRG1 are common causes of osteopetrosis. HCl secretion is dependent on chloride
      channels; a chloride channel homologue, CLCN7, is another common defect in
      osteopetrosis. Humans who are deficient in carbonic anhydrase II or who have
      defects in phagocytosis also have variable defects in bone remodelling. Organic
      bone matrix is degraded by thiol proteinases, principally cathepsin K, and
      abnormalities in cathepsin K cause another sclerotic bone disorder,
      pycnodysostosis. Thus, bone turnover in normal subjects depends on relative
      expression of key cytokines, and defects in osteoclastic turnover usually reflect
      defects in specific ion transporters or enzymes that play essential roles in bone
      degradation.

PMID- 14702188
TI  - Regeneration of heart muscle tissue: quantification of chimeric cardiomyocytes
      and endothelial cells following transplantation.
AB  - Persuasive evidence has been recently provided that adult bone marrow (BM) cells
      exert greater plasticity than previously assumed. This review is focused on the
      quantification of mixed chimerism (mCh) in the hearts (cardiomyocytes and
      endothelial cells) of patients after orthotopic heart to heart transplantation
      (HHT) in comparison to full (unmanipulated) allogeneic BM and peripheral blood
      stem cell (PBSC) transplants. Following a sex-mismatched transplantation
      constellation heart muscle tissue obtained at autopsy was examined. Evaluation of
      mCh was most often performed by immunophenotyping combined with fluorescence in
      situ hybridization (FISH) applying x- and y-chromosome-specific DNA probes. When
      comparing our data with the results of former studies that were regularly based
      on the detection of the y-chromosome alone, the quantity of chimeric
      cardiomyocytes after HHT ranged from 0% to 9%. On the other hand, after full BM
      transplantats (chimeric) cardiomyocytes of donor-type origin appeared at an
      incidence between 0.23% to 6.4%. These disturbing inconsistencies were assumed to
      be related to methodology: the restriction to the y-chromosome, disregard of the
      plane of section (detection sensitivity ranging between 35% and 67%) and state of
      tissue preservation (cadaver hearts). Therefore, when strictly applying dual
      color FISH and limiting the recognition of chimeric cardiomyocytes and
      endothelial cells to the presence of two distinctive signals detection
      sensitivity was significantly enhanced. Contrasting a total congruence with the
      genotyping in control specimens of normal cadaver hearts, a striking disparity in
      the extent of mCh was found depending on the different modes of transplantation.
      After allografting with PBSC a considerably low incidence (1.6%) of chimeric
      cardiomyocytes was determined contrasting with 5.3% of donor-derived cells after
      full BM transplants. Following HHT host-type endothelial cells (16.2%) of the
      intramural and subepicardial vessel walls were more often encountered than
      following BM and PBSC allografting. These findings are in keeping with the
      assumption of a sprouting and migration of vascular structures into the donor
      heart from the site of surgical aligment and injury between retained host and
      donor atrial walls. When considering the other methods of transplantation (BM,
      PBSC) the data on chimeric endothelial cells support the hypothesis of a common
      hemangioblast. Concerning the cardiomyocytes it seems most reasonable to assume
      that primitive mesenchymal stem cells of the BM play a pivotal role in the
      development of mCh. This phenomenon is more extensively expressed than previously
      expected and may be related to an enforced repair of the damaged myocardium
      during the post-transplant period as the sequel of myeloablative (cardiotoxic)
      conditioning.

PMID- 14702189
TI  - Histopathology, pathogenesis and molecular genetics in primary central nervous
      system lymphomas.
AB  - Recent increases in the incidence of primary central nervous system lymphoma
      (PCNSL), a rare non-Hodgkin's lymphoma arising in the brain, have been noted in
      both immunodeficient and immunocompetent patients. Compared with lymphomas
      originating outside the central nervous system, the biology of PCNSL at the
      molecular or cytogenetic level has not been well characterized, yet it is
      important to thoroughly understand the etiology of this rare malignant lymphoma
      if effective therapies are to be developed. This review will focus on the
      epidemiology, clinical aspects, histopathology, pathogenesis, and molecular
      genetics of this aggressive, extranodal lymphoma in immunocompetent patients.

PMID- 14702190
TI  - Promoter methylation status of tumor suppressor and tumor-related genes in
      neoplastic and non-neoplastic gastric epithelia.
AB  - A number of tumor suppressor and tumor-related genes exhibit promoter
      hypermethylation with resulting gene silencing in human cancers. In addition,
      several gene promoters have also been shown to become hypermethylated in non
      neoplastic cells during aging. To assess the physiological consequence and
      clinical significance of gene promoter methylation in gastric epithelia, our
      laboratory has studied the methylation status of tumor suppressor and tumor
      related genes, including APC, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16,
      PTEN, RASSF1A, RUNX3 and TSLC1, in neoplastic and non-neoplastic gastric
      epithelia. The tumor suppressor and tumor-related genes, except APC, were
      generally unmethylated in non-neoplastic gastric epithelia obtained from younger
      individuals. The frequencies of methylation increased with age to varying degrees
      in various genes, although GSTP1 and PTEN methylation was completely absent in
      both neoplastic and non-neoplastic gastric epithelia. The methylation frequencies
      in each gene were found to be comparable in neoplastic and non-neoplastic gastric
      epithelia, except the methylation of RUNX3 and TSLC1, which was mostly cancer
      specific (P<0.01). When methylation frequencies were compared between non
      neoplastic gastric epithelia from cancer-bearing and non-cancer-bearing stomachs,
      hMLH1 and p16 methylation was more frequent in those from cancer-bearing stomachs
      (P<0.01). Promoter methylation in tumor suppressor and tumor-related genes
      initially occurs in non-neoplastic gastric epithelia, increases with age, and
      ultimately silences gene function to constitute a field-defect that may
      predispose tissues to gastric cancer evolution. In clinical applications RUNX3
      and TSLC1 methylation may be utilized as molecular diagnostic markers, and hMLH1
      and p16 methylation as predictors of malignancy in the stomach.

PMID- 14702191
TI  - Multicolor FISH probe sets and their applications.
AB  - Multicolor fluorescence in situ hybridization (FISH) assays are nowadays
      indispensable for a precise description of complex chromosomal rearrangements.
      Routine application of such techniques on human chromosomes started in 1996 with
      the simultaneous use of all 24 human whole chromosome painting probes in
      multiplex-FISH (M-FISH) and spectral karyotyping (SKY). Since then different
      approaches for chromosomal differentiation based on multicolor-FISH (mFISH)
      assays have been described. Predominantly, they have been established to
      characterize marker chromosomes identified in conventional banding analysis.
      Their characterization is of high clinical impact and is the requisite condition
      for further molecular investigations aimed at the identification of disease
      related genes. Here we present a review on the available mFISH methods including
      their advantages, limitations and possible applications.

PMID- 14702192
TI  - Therapy-related changes of the bone marrow in chronic idiopathic myelofibrosis.
AB  - In chronic myeloproliferative disorders (CMPDs) a conflict of opinion exists
      regarding therapy-induced bone marrow (BM) changes and the evolution of
      myelofibrosis during the lengthy course of the disease. For a more elaborate
      study of these features chronic idiopathic myelofibrosis (IMF) seems to be a most
      suitable condition. Therefore this review is focused on this CMPD and amongst
      other findings analyzes data from a series of 340 patients with a long follow-up
      including 893 biopsies (median interval of 32 months). The ensuing results were
      compared with those communicated in the relevant literature. In addition to a
      control group of 153 patients with IMF who received only symptomatic treatment,
      therapy groups included busulfan, hydroxyurea, interferon and various
      combinations. In all groups hypoplasia of a varying degree was a frequent finding
      (6%) and often accompanied by a patchy arrangement of hematopoiesis. Most
      conspicuous was a gelatinous edema showing a tendency to develop a discrete
      reticulin fibrosis (scleredema). Aplasia developed in 7.7% of patients, usually
      at terminal stages of the disease independently of treatment. Minimal to moderate
      maturation defects of hematopoiesis involved especially megakaryocytes and
      erythroid precursors, but overt myelodysplastic features were most prominent
      following hydroxyurea and busulfan therapy. Acceleration and blastic crisis were
      characterized not only by increasing dysplastic changes, but also by the
      appearance of blasts including CD34+ cells. Semiquantitative grading of the fiber
      content revealed that 183 patients (54%) without or with moderate fibrosis at the
      beginning showed a significant progression and therefore contrasted with the 66
      patients with a stable state. Following this calculation no relevant differences
      in the evolution of myelofibrosis were evident in the various therapy groups
      especially not following interferon treatment. In a few patients a regression was
      found which was accompanied by a severe hypoplasia or aplasia compatible with a
      myelo-ablative effect. In conclusion, peculiar BM changes, in particular
      conspicuously expressed myelodysplastic features are consistent with therapy
      related lesions. Development of myelofibrosis in IMF is obviously due to disease
      progression unrelated to stage at diagnosis and not significantly influenced by
      treatment modalities.

PMID- 14702193
TI  - Attachment of the soluble complement regulator factor H to cell and tissue
      surfaces: relevance for pathology.
AB  - Complement is a central element of innate immunity and this vital defense system
      initiates and coordinates immediate immune reactions which attack and eliminate
      microbes, foreign particles and altered self cells. Newly generated activation
      products are extremely toxic and consequently, activation is highly restricted in
      terms of time and space. The initial activation of the alternative complement
      pathway occurs continuously and the early phase acts indiscriminatoryl and forms
      on any surface. However, the system discriminates between self and foreign, and
      therefore allows activation on foreign surfaces e.g. microbes, and restricts
      activation on host cells. Consequently, self cells and tissues are protected from
      the harmful activation products. This protection is mediated by specific
      regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound
      forms. Here we review a novel mechanism, i.e. the attachment of the soluble
      complement regulator factor H to the surface of self cells. This attachment,
      which is demonstrated experimentally by means of immunofluorescense microscopy
      and by flow cytometry, increases the inhibitory potential at the cell surface and
      mediates protection by reducing the local formation of toxic inflammatory
      products. This attachment is highly relevant and has pathophysiological
      consequences in several human diseases, including Factor H-associated hemolytic
      uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II,
      recurrent microbial infections and chronic inflammation, e.g. rheumatoid
      arthritis and immune evasion of tumor cells. Defects of this safeguard activity
      have been recently understood in patients with FH-HUS. Point mutations in the
      Factor H gene occurring in the C-terminus of the protein result in impaired cell
      binding capacity of Factor H and, consequently, during an inflammatory insult
      endothelial cells are not properly protected and are damaged.

PMID- 14702194
TI  - The mast cell: an active participant or an innocent bystander?
AB  - Mast cells (MC) are phylogenetically old cells which are distributed throughout
      the human organism and, on the whole, occupy roughly the volume of the spleen. MC
      have long been recognized as key cells of type I hypersensitivity reactions.
      Several lines of evidence, however, indicate that they not only express critical
      effector functions in classic IgE-associated allergic disorders, but also play
      important roles in host defence against parasites, bacteria and perhaps even
      viruses. Indeed, it is now clear that MC can contribute to host defence in the
      context of either acquired or innate immune responses through the release of a
      myriad of pro-inflammatory and immunoregulatory molecules and the expression of a
      wide spectrum of surface receptors for cytokines and chemokines. Moreover, there
      is growing evidence that MC exert distinct non-immunological functions, playing a
      relevant role in tissue homeostasis, remodeling and fibrosis as well as in the
      processes of tissue angiogenesis. In this review, we provide a small insight into
      the biology of human MC and their potential implications in clinical pathology.

PMID- 14702195
TI  - Neural stem cells and the quest for restorative neurology.
AB  - A great deal of interest has attracted the attention of researchers on the
      potential use of (neural) stem cells in cell replacement or restorative therapies
      for heretofore incurable CNS pathologies such as brain stroke, spinal cord
      injury, Parkinson's disease or multiple sclerosis. This short perspective
      illustrates our view of neural stem cell research with a focus on the stem cell
      concept, on the in situ identity of neural stem cells and on selected aspects of
      embryonic and adult neurogenesis. A brief survey of current stem cell-based
      experimental literature tries to provide a realistic picture of how far we have
      gone in the quest to establish a restorative neurology.

PMID- 14702196
TI  - Ischemic preconditioning: tolerance to hepatic ischemia-reperfusion injury.
AB  - Hepatic ischemia-reperfusion (I/R) injury still remains an unresolved problem in
      both liver resectional surgery and liver transplantation and may be responsible
      for liver failure, lung injury and death. The current review summarizes the
      findings reported to date on the effectiveness of ischemic preconditioning
      against liver and lung damage associated with hepatic I/R injury and the
      underlying protective mechanisms. The effect of ischemic preconditioning on the
      mechanisms potentially involved in hepatic I/R injury, including alterations in
      energy metabolism, neutrophil accumulation, microcirculatory disturbances,
      formation of proinflammatory mediators, such as endothelin and tumor necrosis
      factor-alpha, and reactive oxygen species generation have been evaluated. In this
      review, we address the role of preconditioning in the increased vulnerability of
      fatty livers to hepatic I/R injury. The effectiveness of ischemic preconditioning
      versus pharmacological strategies that could simulate the benefits of liver
      preconditioning has been also discussed.

PMID- 14702197
TI  - Symmetry applied to nuclear microanatomy: a review of gene function and cell
      differentiation.
AB  - The purpose of this paper is to review current knowledge and understandings of
      gene control and cell differentiation, based upon an appreciation of a possible
      role that nuclear microanatomy and considerations of steric symmetry might play.
      Metaphase sister chromatids have identical base codes but show a mirror image
      symmetry of higher order coiling. Chromosomes in the interphase nucleus have
      spatially well defined domains and are anatomically distinct and ordered.
      Chromosomes are known to have interactions i.e. sex chromosome inactivation, PEV,
      etc. An hypothesis of gene activation is made based on steric interactions among
      chromosomes and between chromosomes and activating and repressor proteins. These
      interactions may be influenced by the handedness of higher order chromatid
      coiling, since homologues show mirror-image symmetrical coiling in metaphase,
      which might be retained to a certain degree in interphase. This may result in a
      binary switching of genes. All possible combinations of chromatids in the
      interphase nucleus, would be enabled by a differential segregation of homologous
      chromatids at mitosis. To conserve patterns of interchromatid interactions, there
      must be a programmed segregation of chromatids towards one of the two spindle
      pole attachments. This orientation might be effected by preferential attachment
      of microtubules to kinetochore attachment sites, by steric hindrance of the
      kinetochore by condensed chromatin which initially allows only unidirectional
      tubule attachment, or possibly by a tethering of interacting chromatids which
      would migrate en masse. An attempt to apply this hypothesis to some illustrative
      pathological conditions is made.

PMID- 14702198
TI  - SDF-1 and CXCR4 in normal and malignant hematopoiesis.
AB  - Over recent years it has become apparent that the chemokine SDF-1 and its
      receptor CXCR4 play pivotal roles in normal hematopoiesis. They are essential for
      the normal ontogeny of hematopoiesis during embryogenesis and continue to play a
      key role in retaining hematopoietic progenitors within the bone marrow
      microenvironment in the adult. As a result of this role disruption of SDF-1/CXCR4
      interactions results in mobilization of hematopoietic progenitors and standard
      mobilization protocols disrupt this axis. Similarly SDF-1/CXCR4 interactions are
      required for homing and engraftment of hematopoietic stem cells during
      transplantation. SDF-1 regulates the localisation of leukemic cells and like
      their normal counterparts most leukemic cells respond to SDF-1 with increased
      adhesion, survival and proliferation. However in some instances leukemic cell
      responses to SDF-1 can be disregulated, the impact of which on the progression of
      disease in not known. In this review we discuss the pleiotropic roles of SDF
      1/CXCR4 interactions in human hematopoietic stem cell ontogeny, bone marrow
      homing and engraftment, mobilization and how these interactions impact on
      malignant hematopoiesis.

PMID- 14702199
TI  - The ARF-p53 senescence pathway in mouse and human cells.
AB  - Mouse and human cells have most frequently been used for studies that have led to
      the elucidation of various molecular pathways involved in senescence. The ARF-p53
      pathway has been assigned as one of the major protagonists in these phenomena.
      ARF is an alternative reading frame protein encoded along with p16INK4A by the
      INK4a locus on human chromosome 9p21 and the corresponding locus on mouse
      chromosome 4. Whereas the mouse ARF (p19ARF) consists of 169 amino acids, the
      human ARF (p14ARF) consists of 132 amino acids, truncated at the C-terminus.
      Molecular studies on the regulation of ARF activity by its binding partners have
      revealed that mouse ARF protein, but not human ARF protein, interacts with a
      cytoplasmic protein, Pex19p. This interaction of mouse ARF with Pex19p results in
      its milder p53 activation function in mouse cells as compared to human cells and
      thus accounts, at least in part, for the weaker tumor surveillance and frequent
      immortalization of mouse cells.

PMID- 14702200
TI  - Dendritic cells: sentinels against pathogens.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells, and are
      regarded as "natural adjuvants" for the induction of primary T or T-dependent
      immunity. DCs in the peripheral sites capture and process antigens. Encounter of
      exogenous or endogenous stimuli mature the function of DCs, and they thus acquire
      T-cell stimulatory capacity and distinct chemotactic behavior which enables them
      to migrate to lymphoid tissue. In the secondary lymphoid organs, they present
      antigens to T- and B-cells and stimulate their proliferation. Dendritic cells are
      also involved in tolerance induction, in particular, to self antigens. DCs also
      play a key role in the transmission of many pathogens, and therefore may become
      targets for designing new therapies. DCs have been manipulated in vitro and in
      vivo for cancer immunotherapy. In this article, we provide a concise overview of
      DC biology and its current and future role in clinical settings.

PMID- 14702201
TI  - Post-genomic applications of tissue microarrays: basic research, prognostic
      oncology, clinical genomics and drug discovery.
AB  - Tissue microarrays (TMAs) are an ordered array of tissue cores on a glass slide.
      They permit immunohistochemical analysis of numerous tissue sections under
      identical experimental conditions. The arrays can contain samples of every organ
      in the human body, or a wide variety of common tumors and obscure clinical cases
      alongside normal controls. The arrays can also contain pellets of cultured tumor
      cell lines. These arrays may be used like any histological section for
      immunohistochemistry and in situ hybridization to detect protein and gene
      expression. This new technology will allow investigators to analyze numerous
      biomarkers over essentially identical samples, develop novel prognostic markers
      and validate potential drug targets. The ability to combine TMA technology with
      DNA microarrays and proteomics makes it a very attractive tool for analysis of
      gene expression in clinically stratified tumor specimens and relate expression of
      each particular protein with clinical outcome. Public domain software allows
      researchers to examine digital images of individual histological specimens from
      TMAs, evaluate and score them and store the quantitative data in a relational
      database. TMA technology may be specifically applied to the profiling of proteins
      of interest in other pathophysiological conditions such as congestive heart
      failure, renal disease, hypertension, diabetes, cystic fibrosis and
      neurodegenerative disorders. This review is intended to summarize the strengths
      and weaknesses of TMA technology which will have an increasingly important role
      in the laboratories of the post-genomic era.

PMID- 14702203
TI  - Correlation of motor nerve conduction velocity and number of innervated muscle
      fibers.
AB  - Distal and proximal motor (M) responses were recorded from the "Abductor Pollicis
      Brevis" (APB) muscle by using the collision method; median motor nerve was
      stimulated at distal (elbow) and proximal (wrist) regions in a concurrent manner.
      The delay between two stimuli (ISI: Inter-stimulus Interval), beginning at 9 ms,
      was decreased by 0.1 ms steps, until the proximal potential completely
      disappeared. Areas of M responses recorded for each ISI were calculated. Because
      the area difference between two subsequent ISIs is proportional to the number of
      muscle fibers innervated by the conduction velocity group at that interval, the
      relative numbers of muscle fibers for each velocity group were calculated. The
      results show that the motor nerve conduction velocities belonging to the
      innervating APB muscle vary between 38 m/s and 57 m/s; the conduction velocity of
      the group innervating the greatest number of muscle nerves was found to be 55-57
      m/s, which comprised 10% of all fibers.

PMID- 14702202
TI  - Identification of ambiguities in the 1994 chronic fatigue syndrome research case
      definition and recommendations for resolution.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability,
      has no confirmatory physical signs or characteristic laboratory abnormalities,
      and the etiology and pathophysiology remain unknown. Difficulties with accurate
      case ascertainment contribute to this ignorance. METHODS: Experienced
      investigators from around the world who are involved in CFS research met for a
      series of three day workshops in 2000, 2001 and 2002 intended to identify the
      problems in application of the current CFS case definition. The investigators
      were divided into focus groups and each group was charged with a topic. The
      investigators in each focus group relied on their own clinical and scientific
      knowledge, brainstorming within each group and with all investigators when focus
      group summaries were presented. Relevant literature was selected and reviewed
      independent of the workshops. The relevant literature was circulated via list
      serves and resolved as being relevant by group consensus. Focus group reports
      were analyzed and compiled into the recommendations presented here. RESULTS:
      Ambiguities in the current CFS research definition that contribute to
      inconsistent case identification were identified. Recommendations for use of the
      definition, standardization of classification instruments and study design issues
      are presented that are intended to improve the precision of case ascertainment.
      The International CFS Study Group also identified ambiguities associated with
      exclusionary and comorbid conditions and reviewed the standardized,
      internationally applicable instruments used to measure symptoms, fatigue
      intensity and associated disability. CONCLUSION: This paper provides an approach
      to guide systematic, and hopefully reproducible, application of the current case
      definition, so that case ascertainment would be more uniform across sites.
      Ultimately, an operational CFS case definition will need to be based on empirical
      studies designed to delineate the possibly distinct biological pathways that
      result in chronic fatigue.

PMID- 14702204
TI  - Somatosensory conduction velocity distribution of median nerve middle palmar
      digital component.
AB  - Collision technique is one of the methods used to obtain the relative number of
      fibers in a nerve bundle. In 25 normal subjects, the right median nerve has been
      concurrently stimulated at proximal (elbow) and distal (wrist) locations, and the
      resultant compound action potentials (CAP) were recorded at the middle finger via
      ring electrodes. The delay between the two stimuli (Inter Stimulus Interval;
      ISI), beginning from 7 ms, has been decreased in 0.1 ms steps, until the CAPs,
      elicited by proximal stimulation, totally disappeared. The obtained data have
      been transferred to computer medium for further analysis. In this procedure,
      areas under proximal CAPs have been obtained for each ISI value. Using these
      areas, the relative numbers of fibers (%) belonging to the middle proper palmar
      digital (MPPD) component of sensory median nerve have been derived. The mean
      conduction velocities in MPPD component of sensory median nerve ranged from 40
      m/s to 68 m/s. In the histogram,  a large amount of heaping of the relative
      number of fibers has been observed in 48-59 m/s conduction velocity interval with
      the ratio of 64%, although there has been a 21% group having 43-47 ms conduction
      velocity. These results can be a guide to future studies concerning basic and
      clinical nerve conduction studies.

PMID- 14702205
TI  - Cranial computed tomography in purulent meningitis of childhood.
AB  - The cranial computed tomography (CT) findings of 48 children with purulent
      meningitis were examined, prospectively, to determine the importance of cranial
      CT findings on the prognosis of childhood meningitis, in a developing country.
      The age of children ranged from 2 months to 13 years. Of 48 patients, 29 (60.5%)
      survived without sequelae, 13 (27%) survived with sequelae, and six (12.5%) died.
      Cranial CT was normal in 21 (43%) patients of 48 children with meningitis at
      admission. Abnormal CT findings were detected in 10, 11, and 6 children in the
      groups of survived without sequelae, survived with sequelae, and deaths,
      respectively, at admission (p <.05) We found that CT scan results were correlated
      with neurological signs (p <.05). At least one or more cranial CTs were was re
      taken in children in whom the first CT revealed abnormal findings; we did not
      find a statistically significant difference for the follow-up CT findings between
      the groups (p >.05). Hydrocephalus and subdural effusion were the commonest
      abnormal CT findings. In conclusion, our findings showed that cranial CT may
      safely be used to detect intracranial complications of meningitis in childhood
      and the ratio of sequelae and death were more common in children with abnormal
      cranial CT than those of normal cranial CT findings. Additionally, there was a
      positive correlation between CT scan results and neurological signs.

PMID- 14702206
TI  - Prevalence of Parkinson's disease and parkinsonism in a Colombian population
      using the capture-recapture method.
AB  - Our objective was to estimate the prevalence of Parkinson's disease (PD) and
      Parkinsonism (Ps) in Antioquia (Colombia), using the Capture-Recapture method.
      The two biggest institutions for attending neurological patients in Antioquia
      were selected as sources for the use of the Capture-Recapture method. Prevalences
      of PD (PPD) and Ps (PPs) were estimated according to the following expression:
      PPD (or PPs) = n/Nl105. The number of cases (n) of PD (or Ps), n = a + b + c + d,
      where a = cases identified from the two sources, b = cases identified only in the
      first source, c = cases identified only in the second source, and d = nondetected
      cases from any source = bc/a. The projected Antioquian population for the year
      2000 was used as denominator. Information obtained between January 1, 1996, and
      December 31, 2000, was reviewed in order to identify the clinical records of all
      patients that fulfilled the Ps or PD criteria. General prevalence of PD in
      Antioquia was 30.7/100.000 (C195% = 29.2-32.2), and that of Ps was 42.1/100.000
      (CI95% = 40.3-43.8). Prevalence of PD in people older than 50 years was
      176.4/100.000 (CI95% = 166.6-186.3) and that of Ps was of 339.6/100.000 (C195% =
      326.0-353.2). Ps and PD prevalences in Antioquia were lower than the figures
      reported by the National Neuroepidemiologic Study (470/100.000) and similar to
      the estimated prevalence of these diseases in Caucasian populations (80 to
      270/100.000). These findings evidence the great variability of PD prevalence in
      different regions; therefore, a nationwide study is necessary to determine the
      prevalence of PD and Ps in Colombia.

PMID- 14702207
TI  - The effects of citicoline and lamotrigine alone and in combination following
      permanent middle cerebral artery occlusion in rats.
AB  - The neuroprotective efficacies of citicoline and lamotrigine, alone and in
      combination, were investigated in experimental permanent focal ischemia. Seven
      groups of adult male rats underwent focal cerebral ischemia and were given the
      following treatments: placebo (P), low and high doses of citicoline (C250 and
      C500, 250 and 500 mg/kg/day i.p., respectively), low and high doses of
      lamotrigine (L50 and L100, 50 and 100 mg/kg/day p.o., respectively), and
      combination regimes of both drugs in low (C250 + L50) and high doses (C500 +
      L100). Citicoline, but not lamotrigine, exerted neuroprotective efficacy during
      this acute ischemic stroke model. The citicoline and lamotrigine combination did
      not provide a significant additive neuroprotective effect.

PMID- 14702208
TI  - Astroglial and microglial activation in the wistar rat ventral tegmental area
      after a single striatal injection of 6-hydroxydopamine.
AB  - Astroglial and microglial activation were analyzed in the ventral tegmental area
      (VTA) in adult male Wistar rats, after an unilateral striatal 6-hydroxydopamine
      (6-OHDA) injection. Different doses (8, 4, and 1 microg) of 6-OHDA were injected
      in the left side of the neostriatum; animals were sacrificed 22 days later.
      Control animals received an injection of the same volume of the solvent. The
      tyrosine hydroxylase (TH) positive dopamine cells, the glial fibrillary acidic
      protein (GFAP) immuno -labeled astrocytes, and the OX42 immunoreactive microglia
      were visualized by means of immunohistochemistry and quantified by stereologic
      methods employing the optical dissector and the point intercepts. The number and
      the density of TH immunoreactive cell bodies were decreased by 45% and 46%,
      respectively, in the sampled field of the ipsilateral VTA of 8 microg 6-OHDA
      injected rats. The GFAP immunohistochemistry revealed in the ipsilateral VTA
      increases the number and density of astroglial cells (154% and 166% of control,
      respectively) in the rats with a higher dose of the 6-OHDA, and also in the
      volume fraction of the astroglial processes after 8 microg (41% of control) and 4
      microg (24% of control) of 6-OHDA. Increased number (76% of control) and density
      (77% of control) of OX42 microglial labeled profiles and microglial processes
      (51% of control) were found in the ipsilateral VTA of the 8 microg 6-OHDA
      injected animals. These results suggest that the retrograde degeneration of the
      mesostriatal dopamine pathways, induced by a striatal injection of 6-OHDA, leads
      to astroglial and microglial reactions in the VTA. The interaction between
      activated glial cells may be involved in the wounding and repair events in the
      partial lesioned system, and also in the trophic paracrine responses in the
      surviving VTA dopamine neurons.

PMID- 14702209
TI  - Changes in rat cerebral mitochondrial succinate dehydrogenase activity after
      brain trauma.
AB  - The objective of this study was to evaluate 2,3,5-triphenyltetrazolium chloride
      (TTC) staining in the brain tissue of rats submitted to a closed head traumatic
      injury, in comparison to control rats not submitted to trauma. The closed head,
      weight drop trauma model described by Marmarou et al. (1994) was used. Animals
      were all sacrificed 24 h after trauma. Staining of cerebral coronal slices using
      TTC, coupled to image analysis software, was used to measure the level of
      staining. An ultrastructural study of the brain region underneath the impact
      zone, as well as from the correspondent region of control rats, was also done.
      The TTC image analysis revealed a significant decrease in the percentage of white
      area, in traumatized rats (mean +/- SEM 23.93% +/- 2.26, n = 4 for control,
      12.13% +/- 1.72, n = 9 for traumatized rats, p <.05). The ultrastructural
      analysis revealed that the number of axons showing at least one mitochondrion was
      significantly higher in the trauma group (mean +/- SEM 49.3%, n = 4 rats, 75
      photographs, 2443 axons) than in control groups (23%, n = 3 rats, 30 photographs,
      6220 axons (p <.001). Another difference observed was the larger mitochondrial
      size in the axons of traumatized rats (mean diameter +/- SEM 0.520 +/- 0.003
      microm) compared to the controlled rats (0.368 +/- 0.006 microm; p <.001). The
      ultrastructural observation of the traumatized brain revealed a significantly
      higher number of peroxisomes per photograph (mean number +/- SEM 10.58 +/- 1.18,
      n = 75) compared to the control group (0.19 +/- 0.08, n = 30, p <.001). The
      results indicate an increase of mitochondrial and peroxysomal relative mass, with
      a higher succinate dehydrogenase activity, 24 h after the induction of traumatic
      brain injury.

PMID- 14702212
TI  - Sleep quality and immune functions in rheumatoid arthritis patients with and
      without major depression.
AB  - The purpose of this study was to determine the discriminative factors between
      rheumatoid arthritis (RA) patients with and without major depression (MD). We
      assessed subjective sleep quality, pain, and cell-mediated immune functions in RA
      patients with (n = 20) and without (n = 20) MD by using Pittsburgh Sleep Quality
      Index (PSQI), visual analogue scale (VAS), and fluorescein isothiocyanat (FITC)
      labeled CD3, CD4, CD8, CDI9, CD45, CD56, and HLADR T monoclonal antibodies by
      flow cytometry. We found that the RA patients with MD had significantly higher
      pain level, poorer sleep equality, higher HDRS points, and higher HLADR T cell
      level than those without MD; and that these variables are discriminant factors
      between patient groups. These findings suggest that the RA patients with MD may
      be differentiated from those without MD by using VAS, PSQI, and HLADR levels;
      that these variables correctly classify the depressed and non depressed groups up
      to an accuracy level of 96.8%.

PMID- 14702210
TI  - Venlafaxine-induced depression of wind-up activity in mononeuropathic rats is
      potentiated by inhibition of brain 5-HT1A receptor expression in vivo.
AB  - Antinociceptive effects of inhibiting 5-HT1A receptor expression by
      intracerebroventricular administration of an antisense oligodeoxynucleotide were
      studied in mononeuropathic rats. A 7-day period of treatment with the antisense
      produced: (i) reduction of mechanical hyperalgesia in the neuropathic hindlimb
      starting from day 5 of treatment, (ii) decrease of the hypothermic effect of 8-OH
      DPAT challenge on day 6 of treatment, and (iii) potentiation of the inhibitory
      effect of velafaxine on spinal wind-up activity on day 7 of treatment. Results
      suggest a counteracting role of somatodendritic 5-HT1A receptors of raphe nuclei
      neurons in the antinociceptive efficacy of antidepressants with serotonergic
      spectrum in neuropathic pain.

PMID- 14702214
TI  - Rod and cone signaling transmission in the retina of zebrafish: an erg study.
AB  - It has been suggested that in lower vertebrates, visual signals are propagated in
      the retina using mixed bipolar cell pathways. In this article, we examined rod
      and cone signaling transmission in the retina of teleost zebrafish. Full-field
      electroretinograms (ERGs) were recorded from the cornea of control or 2-amino-4
      phosphonobutyric acid (APB)-treated zebrafish. During dark adaptation following
      bright light adaptation, the intensity-response (V-log I) curve for both the ERG
      b- and d-waves shifted. In control animals, the b-wave response displayed a
      typical visual Purkinje shift and became more sensitive. By contrast, the d-wave 
      became less sensitive. In the early dark adaptation, cone-dominant signals were
      readily recorded in both b- and d-waves. In the late dark adaptation, rod signals
      became dominant. However, no obvious d-wave was recorded. Intraocular injections
      of APB selectively blocked the b-wave, but revealed the d-wave in both early and
      late dark adaptation.

PMID- 14702216
TI  - Attention deficit/hyperactivity disorder and working memory in clinically
      referred adults.
AB  - A current theory of attention deficit/hyperactivity disorder (ADHD) implicates a
      dysfunction in working memory as a significant factor in ADHD. The Working Memory
      Indexes of the Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; The
      Psychological Corporation, 1997a) and the Wechsler Memory Scale--Third Edition
      (WMS-III; The Psychological Corp -oration, 1997b) were used to evaluate this
      theory. Seventy adults clinically diagnosed with ADHD (mean age = 25) and who
      were previously administered the WAIS-III and WMS-III were reviewed to determine
      the association between working memory and ADHD symptomology. The respondent was
      asked to estimate the frequency of occurrence of ADHD symptoms by completing the
      Brown ADD Scales (Brown, 1996). Results indicated no significant relationship
      between working memory and self-reported symptoms, although the Working Memory
      Indexes of the WAIS-III and the WMS-III were significantly correlated.
      Implications for current ADHD theory and suggestions for future research were
      discussed.

PMID- 14702218
TI  - Child psychiatry, mental disorder and the law: is a more specific statutory
      framework necessary?

PMID- 14702219
TI  - Towards integrated health care: a model for assault victims.

PMID- 14702220
TI  - The principle of equivalence and the future of mental health care in prisons.

PMID- 14702221
TI  - ADHD is best understood as a cultural construct.

PMID- 14702222
TI  - Globalisation and mental disorders. Overview with relation to depression.
AB  - BACKGROUND: Globalisation is the process by which traditional boundaries of
      cultures are changing. Industrialisation, urbanisation and influence of the media
      are influencing idioms of distress across cultures. AIMS: To discuss the role of
      globalisation, using the epidemiology, diagnosis, clinical presentation and
      treatment of depression across various cultures as an example. METHOD: Recent
      studies focusing on transcultural aspects of depression were reviewed and
      summarised. RESULTS: Cultural, social and religious mores account for variations
      in the presentation of depression across cultures. Somatic symptoms are common
      presenting features throughout the world and may serve as cultural idioms of
      distress, but psychological symptoms can usually be found when probed. Feelings
      of guilt and suicide rates vary across cultures and depression may be
      underdiagnosed. CONCLUSIONS: Training packages could enhance clinicians'cultural
      competency in multicultural settings. However, globalisation is likely to
      influence idioms of distress and pathways to care in ways that are difficult to
      predict.

PMID- 14702223
TI  - Lone mothers' experience of physical and sexual violence: association with
      psychiatric disorders.
AB  - BACKGROUND: Violence against women is increasingly recognised as an important
      issue in both research and social policy. AIMS: To assess the lifetime experience
      of physical and sexual violence among lone and partnered mothers and the
      association with psychiatric disorders. METHOD: Analysis of the Australian
      National Survey of Mental Health and Wellbeing. The representative sample
      included 2232 women with children who completed the Composite International
      Diagnostic Interview, a scale of psychological distress and sociodemographic
      measures. RESULTS: Lone mothers were more likely to have psychiatric disorders
      (odds ratios between 2.4 and 3.4) and have experienced physical and sexual
      violence (odds ratios between 3.1 and 4.1) than partnered mothers. The measures
      of physical and sexual violence were better predictors of psychiatric disorders
      than either lone parent status or the sociodemographic measures. CONCLUSIONS:
      Experience of physical and sexual violence accounted for much of the greater
      prevalence of psychiatric disorders among lone compared with partnered mothers.

PMID- 14702224
TI  - Birth weight and later risk of depression in a national birth cohort.
AB  - BACKGROUND: Low birth weight increases the risk of childhood behavioural
      problems, but it is not clear whether poor foetal growth has a long-term
      influence on susceptibility to depression. AIMS: To examine the relation between
      birth weight and risk of psychological distress and depression. METHOD: At age 16
      years 5187 participants in the 1970 British Cohort Study completed the 12-item
      General Health Questionnaire to assess psychological distress. At age 26 years
      8292 participants completed the Malaise Inventory to assess depression and
      provided information about a history of depression. RESULTS: Women whose birth
      weight was </=3 kg had an increased risk of depression at age 26 years (OR=1.3;
      95% CI1.0-1.5) compared with those who weighed >3.5 kg. Birth weight was not
      associated with a reported history of depression or with risk of psychological
      distress at age 16 years. In men there were no associations between any
      measurement and the full range of birth weight but, compared with men of normal
      birth weight, those born weighing </=2.5 kg were more likely to be
      psychologically distressed at age 16 years (OR=1.6,95% CI1.1-2.5) and to report a
      history of depression at age 26 years (OR=1.6,95% CI1.1-2.3). CONCLUSIONS:
      Impaired neurodevelopment during foetal life may increase susceptibility to
      depression.

PMID- 14702225
TI  - Ethnoepidemiology of postnatal depression. Prospective multivariate study of
      sociocultural risk factors in a Chinese population in Hong Kong.
AB  - BACKGROUND: Although there have been many studies of the biological and
      psychosocial causations of postnatal depression, studies of sociocultural risk
      factors are rare. AIMS: To investigate the sociocultural risk factors of
      postnatal depression using ethnographically informed epidemiological methods.
      METHOD: A total of 959 women were assessed at their first ante-partum visit
      (baseline), in the third trimester, immediately after delivery, and 3 months
      postpartum. Six domains of risk factors were examined. The dependent variable was
      postnatal depression (as defined by the Edinburgh Postnatal Depression Scale) at
      3 months post-partum. RESULTS: Conflict with mother-in-law, marital
      dissatisfaction, past depression and antenatal depression independently predicted
      the occurrence of postnatal depression. The cultural practice of peiyue - a
      Chinese post-partum custom of mandated family support - was associated with
      better social support and a slightly lower risk of postnatal depression.
      CONCLUSIONS: Sociocultural aspects of the immediate puerperium shape maternal
      emotional well-being. In-law conflict is an important source of household
      distress in many Asian societies. The findings have implications for clinical
      practice and future studies.

PMID- 14702226
TI  - Antidepressant-related deaths and antidepressant prescriptions in England and
      Wales, 1998-2000.
AB  - BACKGROUND: Deaths from antidepressants continue to account for a substantial
      proportion of drug-related deaths. AIMS: To investigate the relative toxicity of
      the major classes of antidepressant drugs, with the specific objective of
      assessing this in relation to the cause of death; and to analyse the deaths where
      there were multiple mentions of antidepressant drugs or other psychoactive drugs
      with antidepressants. METHOD: Mortality data were collected from the National
      Programme of Substance Abuse Deaths, and antidepressant prescription data were
      collected. RESULTS: Most deaths from antidepressant drugs were suicides (80%).
      Tricyclic antidepressants (TCAs) accounted for more drug mentions than did other
      antidepressant drugs (12 per million prescriptions). Selective serotonin reuptake
      inhibitors (SSRIs) were associated with a significantly lower risk of toxicity,
      but 93% of deaths from SSRIs occurred in combination with other drugs, especially
      TCAs (24.5%). In 'combination' deaths patients were significantly more likely to
      have had a history of drug misuse. CONCLUSIONS: The efficacy and safety of
      augmentation therapy with TCAs in SSRI-resistant patients should be monitored
      carefully, and patients prescribed antidepressants should be screened for drug
      use/misuse.

PMID- 14702227
TI  - Heterogeneity of outcomes in schizophrenia. 3-year follow-up of treated prevalent
      cases.
AB  - BACKGROUND: Care for people with schizophrenia should address a wide range of
      outcomes, including professional and consumer perspectives. AIMS: To measure
      changes in psychopathology, functioning, needs for care and quality of life; to
      develop predictive models for each outcome domain; and to assess the frequency of
      'good'and'poor' outcomes, as defined in a series of different definitions that
      use combinations of the four domains measured. METHOD: Three-year follow-up of a
      1-year-treated prevalence cohort of 107 patients with an ICD-10 diagnosis of
      schizophrenia attending the South Verona community-based mental health service.
      RESULTS: Mean symptom severity and some types of needs for care worsen, but
      quality of life shows no change. Functioning shows a non-significant trend to
      deteriorate. Between 32% and 42% of the variance in the four key outcomes was
      explained by our model. Different definitions of 'good'and 'poor' outcome
      included 0-31% of patients, depending on the definition used. CONCLUSIONS: The 3
      year outcome for schizophrenia depends on the domain of outcome used, whether
      staff or patient ratings are used and the stringency of the definitions used for
      good and poor outcome.

PMID- 14702228
TI  - Effects of antipsychotics on fat deposition and changes in leptin and insulin
      levels. Magnetic resonance imaging study of previously untreated people with
      schizophrenia.
AB  - BACKGROUND: Weight gain is a common consequence of antipsychotic drug treatment
      and can lead to further morbidity. AIMS: To assess the effects of antipsychotic
      drug therapy on abdominal fat deposition, on insulin and leptin secretion, and on
      circulating glucose and lipids. METHOD: Abdominal body fat was determined by
      magnetic resonance imaging in a group of previously untreated patients with
      schizophrenia, before and after 10 weeks' antipsychotic drug treatment. Body mass
      and blood concentrations of glucose, insulin, leptin and lipids were also
      measured. RESULTS: Significant increases in both subcutaneous and intra-abdominal
      fat were identified after antipsychotic drug treatment. A three-fold increase in
      leptin secretion as well as significant increases in levels of circulating lipids
      and non-fasting glucose were also identified. CONCLUSIONS: Patients first
      receiving antipsychotic drugs experience substantial deposition of both
      subcutaneous and intra-abdominal fat, reflecting a loss of the normal inhibitory
      control of leptin on body mass. Along with fat deposition, the increase in levels
      of fasting lipids and in non-fasting glucose may provide early signs of drug
      induced progression towards the metabolic syndrome.

PMID- 14702229
TI  - Early cognitive-behavioural therapy for post-traumatic stress symptoms after
      physical injury. Randomised controlled trial.
AB  - BACKGROUND: Early single-session psychological interventions, including
      psychological debriefing following trauma, have not been shown to reduce
      psychological distress. Longer early psychological interventions have shown some
      promise. AIMS: To examine the efficacy of a four-session cognitive-behavioural
      intervention following physical injury. METHOD: A total of 152 patients attending
      an accident and emergency department displaying psychological distress following
      physical injury were randomised 1-3 weeks post-injury to a four-session cognitive
      behavioural intervention that started 5-10 weeks after the injury or to no
      intervention and then followed up for 13 months. RESULTS: At 13 months, the total
      Impact of Event Scale score was significantly more reduced in the intervention
      group (adjusted mean difference=8.4,95% CI 2.4-14.36). Other differences were not
      statistically significant. CONCLUSIONS: A brief cognitive-behavioural
      intervention reduces symptoms of post-traumatic stress disorder in individuals
      with physical injury who display initial distress.

PMID- 14702230
TI  - Mental health survey of the adult population in Iran.
AB  - BACKGROUND: No national data on the prevalence of mental disorders are available
      in Iran. Such information may be a prerequisite for efficient national mental
      health intervention. AIMS: To determine the mental health status of a population
      sample aged 15 years and over. METHOD: Through random cluster sampling, 35 014
      individuals were selected and evaluated using the 28-item version of the General
      Health Questionnaire. A complementary semi-structured clinical interview was also
      undertaken to detect learning disability ('mental retardation'), epilepsy and
      psychosis. RESULTS: About a fifth of the people in the study (25.9% of the women
      and 14.9% of the men) were detected as likely cases. The prevalence of mental
      disorders was 21.3% in rural areas and 20.9% in urban areas. Depression and
      anxiety symptoms were more prevalent than somatisation and social dysfunction.
      The interview of families by general practitioners revealed that the rates of
      learning disability, epilepsy and psychosis were 1.4%, 1.2% and 0.6%,
      respectively. Prevalence increased with age and was higher in the married,
      widowed, divorced, unemployed and retired people. CONCLUSIONS: Prevalence rates
      are comparable with international studies. There is a wide regional difference in
      the country, and women are at greater risk.

PMID- 14702231
TI  - The Child Attention-Deficit Hyperactivity Disorder Teacher Telephone Interview
      (CHATTI): reliability and validity.
AB  - BACKGROUND: The ICD-10 and DSM-IV diagnostic criteria for hyperkinetic disorder
      and attention-deficit hyperactivity disorder (ADHD) require symptoms or
      impairment in two or more settings. Thus, information on children's symptoms in
      school is usually required. This paper presents the Child ADHD Teacher Telephone
      Interview (CHATTI), an instrument aimed at systematically obtaining this
      information. AIMS: To examine the stability, test-retest reliability and
      criterion validity of the CHATTI for children referred with a suspected diagnosis
      of ADHD. METHOD: Data were obtained from 79 teachers, of whom 36 were interviewed
      on two occasions. RESULTS: Overall, the CHATTI shows good stability, test-retest
      reliability and criterion validity for symptom scores. Test-retest reliability
      for some individual items was low. Reliability for the operationalised criteria
      of 'pervasiveness' (i.e. symptoms at school and home) and 'school impairment' was
      excellent (kappa=1). CONCLUSIONS: The CHATTI appears to be a promising tool for
      assessing ADHD symptoms in a school setting and could be useful in clinical as
      well as research settings.

PMID- 14702232
TI  - Evaluation of the Two-Way Communication Checklist as a clinical intervention.
      Results of a multinational, randomised controlled trial.
AB  - BACKGROUND: Patients and doctors often have divergent views on care needs. AIMS:
      To examine whether providing patients with an opportunity to identify and discuss
      their needs would improve communication and induce changes in care. METHOD:
      Patients with schizophrenia (n=134) were randomly allocated to either standard
      care or use of the Two-Way Communication Checklist (2-COM). Before seeing their
      clinician for a routine follow-up, participants in the active intervention group
      were given 2-COM, a list of 20 common needs, and told to indicate those areas
      they wanted to discuss with their doctor. Outcomes were assessed immediately and
      again after 6 weeks. RESULTS: Using 2-COM induced a stable improvement of patient
      reported quality of patient-doctor communication (B=0.33, P=0.031), and induced
      changes in management immediately after the intervention (OR=3.7, P=0.009; number
      needed to treat, 6). Treatment change was more likely inpatients with more
      reported needs, and needs most likely to induce treatment change displayed
      stronger associations with non-medication than with medication changes.
      CONCLUSIONS: A simple intervention to aid people in discussion of their needs
      results in improved communication and changes in management.

PMID- 14702233
TI  - In defence of specialist mental health care trusts.

PMID- 14702234
TI  - Mental incapacity and medical ethics.

PMID- 14702235
TI  - In defence of the case report.

PMID- 14702236
TI  - Cognitive-behavioural therapy for psychosis.

PMID- 14702237
TI  - Debate on neurosurgery.

PMID- 14702238
TI  - Management of post-concussion syndrome.

PMID- 14702239
TI  - Personality assessment.

PMID- 14702241
TI  - Discovering the neural basis of human social anxiety: a diagnostic and
      therapeutic imperative.

PMID- 14702242
TI  - What is a "mood stabilizer"? An evidence-based response.
AB  - OBJECTIVE: The term "mood stabilizer" is widely used in the context of treating
      bipolar disorder, but the U.S. Food and Drug Administration (FDA) does not
      officially recognize the term, and no consensus definition is accepted among
      investigators. The authors propose a "two-by-two" definition by which an agent is
      considered a mood stabilizer if it has efficacy in treating acute manic and
      depressive symptoms and in prophylaxis of manic and depressive symptoms in
      bipolar disorder. They review the literature on the efficacy of agents in any of
      these four roles to determine which if any agents meet this definition of mood
      stabilizer. METHOD: The authors conducted a comprehensive review of English
      language literature describing peer-reviewed, U.S. Agency for Healthcare Research
      and Quality class A controlled trials in order to identify agents with efficacy
      in any of the four roles included in their definition of a mood stabilizer. The
      trials were classified as positive or negative on the basis of primary outcome
      variables. An "FDA-like" criterion of at least two positive placebo-controlled
      trials was required to consider an agent efficacious. The authors also conducted
      a sensitivity analysis by raising and relaxing the criteria for including trials
      in the review. RESULTS: The authors identified 551 candidate articles, yielding
      111 class A trials, including 81 monotherapy trials with 95 independent analyses
      published through June 2002. Lithium, valproate, and olanzapine had unequivocal
      evidence for efficacy in acute manic episodes, lithium in acute depressive
      episodes and in prophylaxis of mania and depression, and lamotrigine in
      prophylaxis (relapse polarity unspecified). Thus, only lithium fulfilled the a
      priori definition of a mood stabilizer. Relaxing the quality criterion did not
      change this finding, while raising the threshold resulted in no agents fulfilling
      the definition. CONCLUSIONS: When all four treatment roles are considered, the
      evidence supported a role for lithium as first-line agent for treatment of
      bipolar disorder. The analysis also highlights unmet needs and promising agents
      and provides a yardstick for evaluating new treatment strategies.

PMID- 14702243
TI  - Maintenance treatment of insomnia: what can we learn from the depression
      literature?
AB  - Insomnia and depression are common problems with profound public health
      consequences. When left untreated, both conditions have high rates of persistence
      and recurrence. Maintenance treatment for depression is fairly well established,
      but there is no evidence-based consensus regarding the safety and efficacy of
      maintenance therapy for insomnia. Consequently, long-term treatment of insomnia
      is driven primarily by the individual choices of patients and their clinicians.
      This article compares and contrasts the current state of research in the
      maintenance therapy of depression and insomnia and highlights gaps in the
      insomnia literature.

PMID- 14702244
TI  - Schizophrenia, IX: Cognition in schizophrenia--the MATRICS initiative.

PMID- 14702245
TI  - Saint Jerome in a dark chamber: Rembrandt's metaphoric portrayal of the depressed
      mind.

PMID- 14702246
TI  - Huntington's disease: phenomenological diversity of a neuropsychiatric condition
      that challenges traditional concepts in neurology and psychiatry.

PMID- 14702248
TI  - The nature of traumatic memories: a 4-T FMRI functional connectivity analysis.
AB  - OBJECTIVE: This study used functional connectivity analyses to assess
      interregional brain activity correlations during the recall of traumatic memories
      in traumatized subjects with and without posttraumatic stress disorder (PTSD).
      METHOD: Both 4-T functional magnetic resonance imaging (fMRI) and functional
      connectivity analyses were used to assess interregional brain activity
      correlations during script-driven symptom provocation in traumatized subjects
      with (N=11) and without (N=13) PTSD. Functional connectivity analyses were
      carried out by using data for brain regions activated in both the PTSD group and
      the comparison group. The use of functional connectivity analyses in addition to
      subtraction analyses allowed assessment of specific brain regions involved in the
      recall of traumatic events and of the neuronal networks underlying the recall of
      such events. RESULTS: Significant between-group differences in functional
      connectivity were found. Comparison of connectivity maps at coordinates x=2,
      y=20, z=36 (right anterior cingulate gyrus) for the two groups showed that the
      subjects without PTSD had greater correlation than the PTSD subjects in the left
      superior frontal gyrus (Brodmann's area 9), left anterior cingulate gyrus
      (Brodmann's area 32), left striatum (caudate), left parietal lobe (Brodmann's
      areas 40 and 43), and left insula (Brodmann's area 13). In contrast, the PTSD
      subjects showed greater correlation than the subjects without PTSD in the right
      posterior cingulate gyrus (Brodmann's area 29), right caudate, right parietal
      lobe (Brodmann's areas 7 and 40), and right occipital lobe (Brodmann's area 19).
      CONCLUSIONS: The differences in brain connectivity between PTSD and comparison
      subjects may account for the nonverbal nature of traumatic memory recall in PTSD
      subjects, compared to a more verbal pattern of traumatic memory recall in
      comparison subjects.

PMID- 14702249
TI  - Posttraumatic stress disorder and health-related quality of life in long-term
      survivors of acute respiratory distress syndrome.
AB  - OBJECTIVE: Intensive care often means exposure to physical and psychological
      stress, with long-lasting emotional sequelae for most patients. Psychiatric
      morbidity and negative effects on health-related quality of life were assessed in
      long-term survivors of acute respiratory distress syndrome. METHOD: Forty-six
      long-term survivors were enrolled in a psychiatric follow-up study. All patients
      had received standard, protocol-driven treatment during intensive care. The
      median follow-up time was 8 years after treatment. DSM-IV was used for
      psychiatric diagnosis. Psychological tests were performed to measure
      posttraumatic stress symptoms; depression; state anxiety; somatization; symptoms
      regarding concentration, attention, and short-term memory; social support; and
      health-related quality of life. RESULTS: At time of discharge, 20 of the patients
      suffered from posttraumatic stress disorder (PTSD) and four from sub-PTSD. At
      follow-up, 11 patients continued to suffer from PTSD and eight from sub-PTSD. The
      patients with PTSD demonstrated a pronounced tendency for somatization and state
      anxiety. Among the groups with PTSD, sub-PTSD, and no PTSD, there were no
      statistically significant differences regarding social support and symptoms of
      cognitive dysfunction. Those with PTSD showed major impairments in some
      dimensions of health-related quality of life, whereas those without PTSD had
      scores that were in the range of the general population. Except for duration of
      stay on the intensive care unit, neither age, gender, sociodemographic variables,
      premorbid psychopathology, nor initial severity of illness discriminated between
      the groups. CONCLUSIONS: Long-term survivors of acute respiratory distress
      syndrome seem to face a major risk of PTSD and major impairments in health
      related quality of life in the long term.

PMID- 14702250
TI  - Social anxiety in outpatients with schizophrenia: a relevant cause of disability.
AB  - OBJECTIVE: Social anxiety is a frequent but often unrecognized feature in
      schizophrenia and is associated with a severe level of disability. To precisely
      define the assessment, impact, clinical correlates, and consequences of social
      anxiety in schizophrenia, the authors conducted a survey of schizophrenia
      patients and a comparison cohort of patients with social anxiety disorder.
      METHOD: A consecutively enrolled group of 80 outpatients with DSM-IV
      schizophrenia and a consecutive comparison group of 27 patients with social
      anxiety disorder were recruited from an institutional psychiatric practice and
      assessed with the Liebowitz Social Anxiety Scale, Scale for the Assessment of
      Negative Symptoms, Scale for the Assessment of Positive Symptoms, Social
      Adjustment Scale, and the Medical Outcomes Study 36-item Short-Form Health
      Survey. RESULTS: Social anxiety scores of schizophrenia patients with comorbid
      social anxiety disorder (N=29, 36.3%) did not differ from those of subjects with
      social anxiety disorder as their primary diagnosis. Schizophrenia patients
      without social anxiety disorder had significantly lower total scores on the
      Liebowitz Social Anxiety Scale and lower social and performance anxiety subscale
      scores than did the other two groups. No differences in negative and positive
      symptom rates were found between schizophrenia patients with and without social
      anxiety disorder. Schizophrenia patients with social anxiety disorder had a
      higher lifetime rate of suicide attempts, greater lethality of suicide attempts,
      more past substance/alcohol abuse disorder, lower social adjustment, and lower
      overall quality of life. CONCLUSIONS: Social anxiety is a highly prevalent,
      disabling condition in outpatients with schizophrenia that is unrelated to
      clinical psychotic symptoms. The Liebowitz Social Anxiety Scale appeared adequate
      and reliable in assessing social anxiety disorder in patients with schizophrenia.
      If these data are confirmed, this study will make a contribution to the search
      for operational guidelines and adequate next-step treatments for social anxiety
      disorder in schizophrenia patients.

PMID- 14702251
TI  - Genome-wide linkage scan for loci predisposing to social phobia: evidence for a
      chromosome 16 risk locus.
AB  - OBJECTIVE: Social phobia is a common, sometimes disabling, fear of situations
      that might entail scrutiny by others. Several anxiety disorders, including social
      phobia, are genetically influenced. Genetic linkage analysis can provide the
      means to identify genomic locations harboring susceptibility loci for genetically
      influenced disorders. Identifying loci for social phobia was the goal of this
      study. METHOD: The authors conducted a genome-wide linkage scan, i.e., tested
      enough genetic markers to query the entire genome, in 17 American pedigrees (163
      subjects) ascertained through probands with panic disorder. Several anxiety
      disorders segregate in these families; diagnoses were based on structured
      interviews. A total of 422 markers (404 autosomal, 18 on the X chromosome) with
      an average spacing of less than 10 centimorgans were genotyped. Multipoint lod
      score and nonparametric (Zlr score) linkage analyses for social phobia were
      completed with Allegro and Genehunter X software. RESULTS: Evidence for linkage
      to social phobia for chromosome 16 markers was identified. A Zlr score of 3.41
      was observed for chromosome 16 near marker D16S415. The maximum observed lod
      score was 2.22, also for chromosome 16, between D16S415 and D16S503 (under a
      model of recessive inheritance). Additional areas of interest were identified on
      chromosomes 9, 14, and 18. CONCLUSIONS: These findings meet conservative criteria
      for "suggestive" linkage. The gene encoding the norepinephrine transporter
      protein (SLC6A2) maps to this broad region, making SLC6A2 both a positional and
      physiological candidate for influencing social phobia risk. To the authors'
      knowledge, this is the first complete linkage genome scan for this disorder.

PMID- 14702252
TI  - Functional magnetic resonance imaging evidence for a lack of striatal dysfunction
      during implicit sequence learning in individuals with animal phobia.
AB  - OBJECTIVE: This study investigated the neural substrates of implicit sequence
      learning in subjects with and without small animal phobia, in a follow-up to
      analogous studies of obsessive-compulsive disorder (OCD). METHOD: Ten subjects
      with specific phobia and 10 healthy comparison subjects were studied by using a
      serial reaction time task paradigm and functional magnetic resonance imaging.
      RESULTS: A main effect of condition (implicit sequence learning versus random
      sequence) was observed across diagnostic groups in the right striatum, as well as
      in other regions. In the striatum, the a priori region of interest, there were no
      significant effects of diagnosis or the interaction of diagnosis and condition.
      CONCLUSIONS: Brain activation in the striatum of subjects with specific phobia
      does not significantly differ from that of normal comparison subjects during
      implicit sequence learning. This suggests different pathophysiological mechanisms
      for specific phobia in contrast to OCD, in which deficient striatal recruitment
      has been reproducibly found with this paradigm. This approach offers promise for
      demonstrating diagnostic specificity across different neuropsychiatric disorders
      based on the presence or absence of deficient striatal activation.

PMID- 14702253
TI  - Left hemisphere dysfunction during verbal dichotic listening tests in patients
      who have social phobia with or without comorbid depressive disorder.
AB  - OBJECTIVE: Behavioral, electrophysiological, and imaging studies have found
      evidence that anxiety disorders are associated with left hemisphere dysfunction
      or higher than normal activation of right hemisphere regions. Few studies,
      however, have examined hemispheric asymmetries of function in social phobia, and
      the influence of comorbidity with depressive disorders is unknown. The present
      study used dichotic listening tests to assess lateralized cognitive processing in
      patients with social phobia, depression, or comorbid social phobia and
      depression. METHOD: The study used a two-by-two factorial design in which one
      factor was social phobia (present versus absent) and the second factor was
      depressive disorder (present versus absent). A total of 125 unmedicated patients
      with social phobia, depressive disorder, or comorbid social phobia and depressive
      disorder and 44 healthy comparison subjects were tested on dichotic fused-words,
      consonant-vowel syllable, and complex tone tests. RESULTS: Patients with social
      phobia with or without a comorbid depressive disorder had a smaller left
      hemisphere advantage for processing words and syllables, compared with subjects
      without social phobia, whereas no difference between groups was found in the
      right hemisphere advantage for processing complex tones. Depressed women had a
      larger left hemisphere advantage for processing words, compared with nondepressed
      women, but this difference was not seen among men. CONCLUSIONS: The results
      support the hypothesis that social phobia is associated with dysfunction of left
      hemisphere regions mediating verbal processing. Given the importance of verbal
      processes in social interactions, this dysfunction may contribute to the stress
      and difficulty experienced by patients with social phobia in social situations.

PMID- 14702254
TI  - Approximate entropy of respiratory patterns in panic disorder.
AB  - OBJECTIVE: Considerable evidence suggests a connection between panic disorder and
      respiration, but the nature of the respiratory abnormalities in panic disorder
      remains unclear. The authors investigated the breath-by-breath complexity of
      respiration dynamics in panic disorder. METHOD: Respiratory physiology was
      assessed in 40 patients with panic disorder and 31 healthy comparison subjects by
      using a breath-by-breath stationary system for testing cardiorespiratory
      function. Irregularity in the breathing pattern was determined by applying the
      approximate entropy index, which is an indicator of the irregularity and the
      "disorder" of the measure. RESULTS: The patients with panic disorder showed
      significantly higher approximate entropy indexes than the healthy subjects for
      the measured respiratory parameters. Sighs contributed to the irregularity of
      breathing patterns but did not account for all the differences in approximate
      entropy between the patients with panic disorder and the comparison subjects.
      Anxiety state, severity of illness, and somatic and individual variables such as
      participation in sports and cigarette smoking did not seem to influence the
      results. CONCLUSIONS: Patients with panic disorder showed greater entropy in
      baseline respiratory patterns, indicating higher levels of irregularity and
      complexity in their respiratory function. Greater respiratory entropy could be a
      factor in vulnerability to panic attacks.

PMID- 14702255
TI  - Panic attacks and psychoticism.
AB  - OBJECTIVE: The authors sought to determine the association between panic attacks
      and psychoticism among young adults in the community. METHOD: Data were drawn
      from a 21-year longitudinal birth cohort study (N=1,265). Negative binomial
      regression models were used to determine the association between panic attacks in
      adolescence (age 15-21) and psychoticism during young adulthood. RESULTS: Having
      a panic attack in the preceding 3 years was associated with elevated rates of
      psychoticism at ages 18 (rate ratio=2.81, 95% CI=1.92-4.13) and 21 (rate
      ratio=3.01, 95% CI=2.10-4.33). These associations were adjusted for differences
      in previous psychoticism, comorbid anxiety, depression, and substance use
      disorders and a range of other potential confounding factors by using a
      generalized estimating equation model. This analysis showed that after adjustment
      for confounding factors, having a panic attack was still associated with an
      increased rate of psychoticism (rate ratio=1.51, 95% CI=1.14-2.02). CONCLUSIONS:
      Panic attacks during adolescence are associated with significantly increased
      levels of psychoticism among young adults in the community compared with young
      persons with no history of panic attacks. Much of the relationship between panic
      attacks and psychoticism appears to be explained by common risk factors and
      psychiatric comorbidity, yet these data provide evidence of an independent
      association between panic attacks in adolescence and psychoticism during young
      adulthood in the community. Replication of these findings is needed, as are
      future studies that further investigate the mechanism of this association.

PMID- 14702256
TI  - Low-field magnetic stimulation in bipolar depression using an MRI-based
      stimulator.
AB  - OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with
      bipolar disorder immediately after they underwent an echo-planar magnetic
      resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within
      clinical MR system limits. This study evaluated possible mood improvement
      associated with this procedure. METHOD: The mood states of subjects in an ongoing
      EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale,
      a structured mood rating scale, immediately before and after an EP-MRSI session.
      Sham EP-MRSI was administered to a comparison group of subjects with bipolar
      disorder, and actual EP-MRSI was administered to a comparison group of healthy
      subjects. The characteristics of the electric fields generated by the EP-MRSI
      scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar
      disorder subjects who received the actual EP-MRSI examination, by three of 10
      bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy
      comparison subjects who received actual EP-MRSI. Significant differences in mood
      improvement were found between the bipolar disorder subjects who received actual
      EP-MRSI and those who received sham EP-MRSI, and, among subjects who received
      actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects
      and to a lesser extent between the unmedicated bipolar disorder subjects and the
      bipolar disorder subjects who were taking medication. The electric fields
      generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in
      repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1
      500 V/m) and also extended uniformly throughout the head, unlike the highly
      nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic
      trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These
      preliminary data suggest that the EP-MRSI scan induces electric fields that are
      associated with reported mood improvement in subjects with bipolar disorder. The
      findings are similar to those for rTMS depression treatments, although the
      waveform used in EP-MRSI differs from that used in rTMS. Further investigation of
      the mechanism of EP-MRSI is warranted.

PMID- 14702257
TI  - Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly
      depressed patients: an MRI-based parcellation of the prefrontal cortex.
AB  - OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal
      cortex in elderly patients with depression, the authors explored differences in
      gray matter, white matter, and CSF volumes by applying a parcellation method
      based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients
      with major depression and 19 group-matched comparison subjects were studied with
      high-resolution MRI. Cortical surface extraction, tissue segmentation, and
      cortical parcellation methods were applied to obtain volume measures of gray
      matter, white matter, and CSF in seven prefrontal subregions: the anterior
      cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal
      cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly
      significant bilateral volume reductions in gray matter were observed in the
      anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed
      patients also exhibited significant bilateral white matter volume reductions and
      significant CSF volume increases in the anterior cingulate and the gyrus rectus.
      Finally, the depressed group showed significant CSF volume reductions in the
      orbitofrontal cortex relative to the comparison subjects. None of the other
      regions examined revealed significant structural abnormalities. CONCLUSIONS: The
      prominent bilateral gray matter deficits in the anterior cingulate and the gyrus
      rectus as well as the orbitofrontal cortex may reflect disease-specific
      modifications of elderly depression. The differential pattern of abnormalities
      detected in the white matter and CSF compartments imply that distinct
      etiopathological mechanisms might underlie the structural cortical changes in
      these regions.

PMID- 14702258
TI  - Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio
      without caspase-3 activation.
AB  - OBJECTIVE: Neuroimaging findings have identified lower cortical gray matter
      volume in schizophrenia. Apoptosis (programmed cell death) has been proposed as a
      contributing pathophysiological mechanism. Levels of antiapoptotic Bcl-2 protein
      are low in the temporal cortex of schizophrenia patients. Bcl-2 interacts with
      the proapoptotic Bax protein at an upstream checkpoint to regulate the activation
      of apoptosis by caspase-3 and other proteolytic caspase proteins. A high Bax/Bcl
      2 ratio is associated with greater vulnerability to apoptotic activation, while a
      high caspase-3 level is often associated with apoptotic activity. It was
      hypothesized that the Bax/Bcl-2 ratio, but not caspase-3, would be high in the
      temporal cortex of patients with chronic schizophrenia. METHOD: Bax, Bcl-2, and
      caspase-3 proteins were measured by semiquantitative Western blot in Brodmann's
      area 21 (middle temporal gyrus) of postmortem tissue from patients with
      schizophrenia (N=15), bipolar disorder (N=15), or major depression (N=15) and
      nonpsychiatric comparison subjects (N=15). RESULTS: The Bax/Bcl-2 ratio was 50%
      higher in the schizophrenia patients than the nonpsychiatric comparison subjects.
      The level of caspase-3 (inactive zymogen and activated subunits) was not
      significantly different. CONCLUSIONS: The higher Bax/Bcl-2 ratio suggests that
      cortical cells are vulnerable to apoptosis in chronic schizophrenia. However, the
      normal caspase-3 level suggests that apoptosis is not active in this illness
      phase. Furthermore, the results appear to distinguish the pathophysiology of
      schizophrenia from most classic neurodegenerative disorders, in which postmortem
      caspase-3 levels are high. Further studies are needed to investigate the
      implications of abnormal apoptotic proteins in schizophrenia.

PMID- 14702259
TI  - Association of anticholinergic load with impairment of complex attention and
      memory in schizophrenia.
AB  - OBJECTIVE: The authors' goals were 1) to establish a clinically useful standard
      index of the relative anticholinergic potency of psychiatric medications; 2) to
      determine which cognitive functions are most affected by the administration of
      anticholinergic medications to patients with schizophrenia; and 3) to compare in
      vitro and clinically derived indexes of anticholinergic load in predicting these
      cognitive impairments. METHOD: One hundred six clinically stable patients with
      schizophrenia were given a brief neuropsychological battery and evaluated on a
      standard symptom rating scale. The anticholinergic load associated with their
      psychiatric medications was estimated by using 1) a pharmacological index,
      calculated from a compilation of published studies reporting in vitro brain
      muscarinic receptor antagonism, and 2) a clinical index, based on clinician
      ratings of the anticholinergic side effects of medications. The authors analyzed
      the correlations of both indexes with the neuropsychological measures and with
      summary neuropsychological factor scores. RESULTS: The clinical and
      pharmacological anticholinergic indexes were highly correlated with each other
      and showed virtually identical associations with neuropsychological measures.
      Anticholinergic load was associated with lower scores on measures of attention
      and declarative memory, including several measures of auditory and visual memory
      and two tests of complex attention, but was unrelated to intelligence, simple
      attention, working memory, executive functions, conceptual fluency, or motor
      speed. CONCLUSIONS: This pattern of cognitive impairment with central cholinergic
      antagonism is consistent with emerging models of the functional anatomy of
      ascending forebrain cholinergic subsystems. Both pharmacological and clinical
      indexes show utility in predicting the effects of anticholinergic load on
      cognition in schizophrenia. Doses of psychiatric medication within the range of
      routine pharmacotherapy practice may have clinically significant effects on
      memory and complex attention in patients with schizophrenia; these effects may
      contribute as much as one-third to two-thirds of the memory deficit typically
      seen in patients with schizophrenia.

PMID- 14702260
TI  - Genetic and neurochemical modulation of prefrontal cognitive functions in
      children.
AB  - OBJECTIVE: The catechol O-methyltransferase (COMT) gene affects how long dopamine
      acts in the prefrontal cortex. The Methionine polymorphism, which results in a
      slower breakdown of prefrontal dopamine, is associated with better adult
      prefrontal cortex function. The authors investigated the relation between the
      COMT gene polymorphism and cognitive performance in children. METHOD: Children
      were tested on cognitive tasks that depend on the dorsolateral prefrontal cortex
      and seem to be sensitive to the level of dopamine there (dots-mixed task), depend
      on that neural region but appear insensitive to its dopamine content (self
      ordered pointing), and depend on other neural systems (recall memory and mental
      rotation). After data collection, cheek swabs were obtained from all children.
      DNA was extracted and genotyped for the COMT gene with polymerase chain reaction.
      RESULTS: Children who were homozygous for the Methionine polymorphism performed
      significantly better on the dots-mixed task but not on others. CONCLUSIONS: The
      findings provide an existence proof that genotypic differences can relate to
      differences in cognitive performance in typically developing children. The
      authors achieved a level of specificity never previously attempted; the COMT
      polymorphism was found to be differentially related to performance on tasks
      linked to the same prefrontal region by whether cognitive requirements of the
      tasks were sensitive to the level of dopamine found. These results challenge
      accepted notions that since dopamine is important for some cognitive functions
      dependent on the prefrontal cortex, it is important for all. The differential
      sensitivity of distinct cognitive abilities to specific neurotransmitters may
      make possible targeted pharmacological interventions.

PMID- 14702261
TI  - Association of the dopamine D4 receptor gene 7-repeat allele with
      neuropsychological test performance of children with ADHD.
AB  - OBJECTIVE: Association between attention deficit hyperactivity disorder (ADHD)
      and the 7-repeat allele of a variant (a 48 bp variable number of tandem repeats)
      in the dopamine D4 receptor gene (DRD4) has been widely documented. A meta
      analysis of 21 studies revealed evidence of significant association. In this
      article the authors examine whether the DRD4 7-repeat allele is associated with
      performance on a variety of neuropsychological tasks in children with ADHD.
      METHOD: The presence or absence of the 7-repeat allele was determined in 133 drug
      naive children 6 to 13 years of age who fulfilled diagnostic criteria for ADHD.
      These children were then assessed on several neuropsychological tests known to be
      associated with attention, impulse control, and response inhibition (the
      Continuous Performance Test, Matching Familiar Figures Test, Go/No Go Task, and
      Stop Task). Activity levels were assessed with an actigraph. Children with and
      without at least one 7-repeat allele were compared with each other and with
      children in a previous population-based study. RESULTS: Children who had the 7
      repeat allele had significantly more incorrect responses on the Matching Familiar
      Figures Test (16.1 versus 14.3) than children who did not have the allele.
      Children with the allele also had shorter mean reaction times for incorrect
      responses on the Matching Familiar Figures Test (846.1 versus 1103.7 msec) and on
      the Stop Task (116.6 versus 134.1 msec) than children without the allele.
      Children with the allele also displayed higher activity levels. The children with
      and without the allele did not differ significantly in number of ADHD symptoms
      when the symptoms were split into the areas of inattention and
      hyperactivity/impulsivity. Both groups of children with ADHD were more
      neuropsychologically impaired than the nonpatient comparison group. CONCLUSIONS:
      In children with ADHD, possession of the DRD4 7-repeat allele appears to be
      associated with an inaccurate, impulsive response style on neuropsychological
      tasks that is not explained by ADHD symptom severity.

PMID- 14702262
TI  - Comparisons of patients with comorbid psychiatric and substance use disorders:
      implications for treatment and service delivery.
AB  - OBJECTIVE: Individuals with co-occurring psychiatric and substance use disorders
      are treated in mental health and substance abuse treatment systems, yet research
      on comorbid disorders rarely includes comparisons across systems. Knowledge about
      patients who share the label "comorbid" but are found in different treatment
      sectors should illuminate service issues and inform policy development.
      Differences across systems should provide support for separate treatments;
      similarities should indicate the value of the integration of services. The
      hypothesis that there are meaningful clinical differences between patients with
      comorbid mental health disorders and patients in drug treatment was tested.
      METHOD: As part of a larger longitudinal study, 106 patients with comorbid
      illness from mental health (N=106) and drug treatment (N=120) settings were
      compared regarding diagnosis, drug use, and problem severity. Data were obtained
      by using the Diagnostic Interview Schedule for DSM-IV and the Addiction Severity
      Index. RESULTS: Few differences between groups emerged. There were no diagnostic
      differences except that schizophrenia spectrum disorders were more common among
      mental health (43%) than drug treatment (31%) patients. Although more drug abuse
      than mental health subjects reported drug use in the 30 days before treatment
      entry, the average number of days of drug use in this period was not different.
      CONCLUSIONS: These findings document the high prevalence of severe mental illness
      in drug treatment clients and of serious drug problems in mental health patients.
      Only minimal differences emerged between the groups and none that indicated need
      for specialized treatments in separate systems of care.

PMID- 14702263
TI  - Quality indicators and monitoring of mental health services: what do frontline
      providers think?
AB  - OBJECTIVE: Many health care organizations are giving feedback to mental health
      care providers about their performance on quality indicators. Mental health care
      providers may be more likely to respond to this feedback if they believe the
      indicators are meaningful and within their "sphere of influence." The authors
      surveyed frontline mental health care providers to elicit their perceptions of
      widely used indicators for quality monitoring in mental health services. METHOD:
      The survey was distributed to a stratified, random sample of 1,094 eligible
      mental health care providers at 52 Department of Veterans Affairs facilities; 684
      (63%) returned the survey. The survey elicited perceptions of 21 widely used
      indicators in five quality domains (access, utilization, satisfaction, process,
      and outcomes). The data were analyzed with descriptive and multivariate methods.
      RESULTS: Most mental health care providers (65%) felt that feedback about these
      widely used indicators would be valuable in efforts to improve care; however,
      only 38% felt able to influence performance related to these monitors and just
      13% were willing to accept incentives/risk for their performance. Providers were
      most positive about satisfaction monitors and preferentially included
      satisfaction, access, and process monitors in performance sets to measure overall
      quality. Despite providers' relatively positive views of monitors, 41% felt that
      monitoring programs did not assist them in improving care. Providers cited
      numerous barriers to improving care processes. CONCLUSIONS: Mental health care
      providers may be more receptive to monitoring efforts if satisfaction, access,
      and process monitors are emphasized. However, providers' views of monitoring
      programs appear to be less affected by concerns about specific monitors than by
      concerns about the accuracy of quality measurement and barriers to changing care
      processes.

PMID- 14702264
TI  - Ventricular enlargement in schizophrenia related to volume reduction of the
      thalamus, striatum, and superior temporal cortex.
AB  - OBJECTIVE: Enlargement of the lateral ventricles is among the most frequently
      reported macroscopic brain structural changes in schizophrenia, although variable
      in extent and localization. The authors investigated whether ventricular
      enlargement is related to regionally specific volume loss. METHOD: High
      resolution magnetic resonance imaging scans from 39 patients with schizophrenia
      were analyzed with deformation-based morphometry, a voxel-wise whole brain
      morphometric technique. RESULTS: Significant negative correlations with the
      ventricle-brain ratio were found for voxels in the left and right thalamus and
      posterior putamen and in the left superior temporal gyrus and insula.
      CONCLUSIONS: Thalamic shrinkage, especially of medial nuclei and the adjacent
      striatum and insular cortex, appear to be important contributors to ventricular
      enlargement in schizophrenia.

PMID- 14702265
TI  - Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological
      deficits.
AB  - OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors
      investigated neuropsychological performance and regional brain volumes in
      schizophrenia patients with high versus low levels of apathy. METHOD:
      Schizophrenia patients with low apathy levels (N=18) and high apathy levels
      (N=20) and 12 healthy comparison subjects completed neuropsychological testing as
      well as magnetic resonance imaging scanning to obtain lobar volumes after total
      intracranial volume was controlled. RESULTS: The high apathy group scored lower
      than comparison subjects on rapid visuomotor sequencing and verbal
      learning/recall. The high apathy group had lower performance IQ scores than the
      low apathy and comparison groups. Only the high apathy group showed significantly
      reduced bilateral frontal lobe volumes relative to comparison subjects; both
      schizophrenia patient groups showed bilateral temporal lobe volume reductions.
      CONCLUSIONS: The present findings are consistent with studies in other disorders
      showing frontal lobe involvement in apathy.

PMID- 14702266
TI  - Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia
      inpatients.
AB  - OBJECTIVE: Since most of the world's schizophrenia patients are treated with
      conventional antipsychotics, the authors evaluated various methods for
      establishing the prevalence of neuroleptic-induced movement disorders in these
      patients. METHOD: DSM-IV criteria and established score thresholds on a movement
      disorder rating scale were used to identify cases of neuroleptic-induced movement
      disorder in a representative Estonian patient sample of 99 chronic
      institutionalized schizophrenia patients, 18-65 years old, treated with
      conventional neuroleptics (79.8%) or clozapine (20.2%). RESULTS: Neuroleptic
      induced movement disorders according to DSM-IV criteria were found in 61.6% of
      the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced
      parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence
      rates for akathisia and tardive dyskinesia were similar when either DSM-IV
      criteria or rating scale scores were used, but the prevalence rate for
      parkinsonism was much lower per DSM-IV criteria than according to rating scale
      score. CONCLUSIONS: Nearly two-thirds of chronic schizophrenia patients suffered
      from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse
      effects still impose a huge burden on the majority of neuroleptic-treated
      individuals with schizophrenia. The discrepancy between the standard
      identification methods for neuroleptic-induced movement disorder indicate the
      need for further research.

PMID- 14702267
TI  - Antidepressant treatment in bipolar versus unipolar depression.
AB  - OBJECTIVE: Antidepressant responses were compared in DSM-IV bipolar and unipolar
      depression. METHOD: The authors analyzed clinical records for outcomes of
      antidepressant trials for 41 patients with bipolar depression and 37 with
      unipolar depression, similar in age and sex distribution. RESULTS: Short-term
      nonresponse was more frequent in bipolar (51.3%) than unipolar (31.6%)
      depression. Manic switching occurred only in bipolar depression but happened less
      in patients taking mood stabilizers (31.6% versus 84.2%). Cycle acceleration
      occurred only in bipolar depression (25.6%), with new rapid cycling in 32.1%.
      Late response loss (tolerance) was 3.4 times as frequent, and withdrawal relapse
      into depression was 4.7 times less frequent, in bipolar as in unipolar
      depression. Mood stabilizers did not prevent cycle acceleration, rapid cycling,
      or response loss. Modern antidepressants, in general, did not have lower rates of
      negative outcomes than tricyclic antidepressants. CONCLUSIONS: The findings
      suggest an unfavorable cost/benefit ratio for antidepressant treatment of bipolar
      depression.

PMID- 14702268
TI  - Normalization of enhanced fear recognition by acute SSRI treatment in subjects
      with a previous history of depression.
AB  - OBJECTIVE: The present study aimed to 1) assess facial expression recognition in
      subjects with a previous history of major depressive disorder relative to
      subjects with no history of depression and 2) characterize the effects of acute
      citalopram infusion on recognition performance for both groups. METHOD:
      Unmedicated euthymic women with a history of major depression and matched
      comparison subjects with no history of depression were given a facial expression
      recognition task following intravenous infusion of saline or citalopram (10 mg)
      in a double-blind, between-group design. RESULTS: Following saline infusion,
      subjects with a previous history of depression showed a selectively greater
      recognition of fear relative to the subjects with no history of depression. The
      abnormal fear processing observed in the subjects with a previous history of
      depression was normalized following citalopram infusion, an effect that was
      opposite to that seen with the subjects with no history of depression.
      CONCLUSIONS: These results suggest that increased recognition of fear is a trait
      vulnerability marker for depression and that this is normalized following a
      single dose of citalopram.

PMID- 14702269
TI  - Double-blind comparison of the continued use of antipsychotic treatment versus
      its discontinuation in remitted manic patients.
AB  - OBJECTIVE: The goal of this study was to determine the benefits of the continued
      use of a typical antipsychotic agent following remission from an acute manic
      episode. METHOD: Immediately following remission of a manic episode treated with
      the combination of a typical antipsychotic (perphenazine) and a mood stabilizer
      (lithium, carbamazepine, or valproate), 37 patients were randomly assigned to 6
      months of double-blind treatment in which in addition to the mood stabilizer they
      received either continued perphenazine treatment or placebo. RESULTS: Patients
      randomly assigned to continue perphenazine treatment, relative to those who
      discontinued it, were more likely to have a shorter time to depressive relapse,
      discontinue the study, and have increased rates of dysphoria, depressive
      symptoms, and extrapyramidal symptoms. CONCLUSIONS: There were no short-term
      benefits with the continued use of a typical antipsychotic after achieving
      remission from an episode of acute mania. In fact, its continued use was
      associated with detrimental effects.

PMID- 14702270
TI  - An open-label trial of riluzole in patients with treatment-resistant major
      depression.
AB  - OBJECTIVE: This study was conducted to determine the efficacy and safety of
      riluzole, a glutamate-modulating agent, in patients with recurrent major
      depression. METHOD: After a 1-week drug-free period, subjects 18 years or older
      with a diagnosis of recurrent major depression and a Montgomery-Asberg Depression
      Rating Scale score > or = 20 received riluzole monotherapy (100-200 mg/day)
      openly for 6 weeks. RESULTS: Nineteen treatment-resistant depressed patients, 53%
      of whom were classified as having stage 2 treatment resistance or greater,
      received riluzole at a mean dose of 169 mg/day. Significant improvement occurred
      during weeks 3 through 6 for all patients and weeks 2 through 6 for completers.
      CONCLUSIONS: Although preliminary, these results indicate that riluzole may have
      antidepressant properties in some patients.

PMID- 14702271
TI  - Clozapine therapy during cancer treatment.

PMID- 14702272
TI  - Ziprasidone-related tardive dyskinesia.

PMID- 14702273
TI  - Higher serum triglyceride levels in early-onset schizophrenia.

PMID- 14702274
TI  - Improvement in PTSD patients who care for their grandchildren.

PMID- 14702288
TI  - Promoter hypermethylation of the cyclin-dependent kinase inhibitor (CDKI) gene
      p21WAF1/CIP1/SDI1 is rare in various lymphomas and carcinomas.

PMID- 14702289
TI  - CD34+ cell dose and the occurrence of GVHD in the presence of in vivo T-cell
      depletion.

PMID- 14702290
TI  - Enough already of the word "robust"!

PMID- 14702291
TI  - Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult
      patients with iron overload: an update.

PMID- 14702292
TI  - Autologous hematopoietic stem cell transplantation for severe/refractory
      intestinal Behcet disease.

PMID- 14702293
TI  - Digging with experimental pick and computational shovel: a new addition to the
      histidine kinase superfamily.

PMID- 14702294
TI  - Isolation and characterization of Burkholderia cenocepacia mutants deficient in
      pyochelin production: pyochelin biosynthesis is sensitive to sulfur availability.
AB  - The opportunistic pathogen Burkholderia cenocepacia produces the yellow-green
      fluorescent siderophore, pyochelin. To isolate mutants which do not produce this
      siderophore, we mutagenized B. cenocepacia with the transposon mini-Tn5Tp. Two
      nonfluorescent mutants were identified which were unable to produce pyochelin. In
      both mutants, the transposon had integrated into a gene encoding an orthologue of
      CysW, a component of the sulfate/thiosulfate transporter. The cysW gene was
      located within a putative operon encoding other components of the transporter and
      a polypeptide exhibiting high homology to the LysR-type regulators CysB and Cbl.
      Sulfate uptake assays confirmed that both mutants were defective in sulfate
      transport. Growth in the presence of cysteine, but not methionine, restored the
      ability of the mutants to produce pyochelin, suggesting that the failure to
      produce the siderophore was the result of a depleted intracellular pool of
      cysteine, a biosynthetic precursor of pyochelin. Consistent with this, the wild
      type strain did not produce pyochelin when grown in the presence of lower
      concentrations of sulfate that still supported efficient growth. We also showed
      that whereas methionine and certain organosulfonates can serve as sole sulfur
      sources for this bacterium, they do not facilitate pyochelin biosynthesis. These
      observations suggest that, under conditions of sulfur depletion, cysteine cannot
      be spared for production of pyochelin even under iron starvation conditions.

PMID- 14702295
TI  - The trp RNA-binding attenuation protein of Bacillus subtilis regulates
      translation of the tryptophan transport gene trpP (yhaG) by blocking ribosome
      binding.
AB  - Expression of the Bacillus subtilis tryptophan biosynthetic genes (trpEDCFBA and
      pabA [trpG]) is regulated in response to tryptophan by TRAP, the trp RNA-binding
      attenuation protein. TRAP-mediated regulation of the tryptophan biosynthetic
      genes includes a transcription attenuation and two distinct translation control
      mechanisms. TRAP also regulates translation of trpP (yhaG), a single-gene operon
      that encodes a putative tryptophan transporter. Its translation initiation region
      contains triplet repeats typical of TRAP-regulated mRNAs. We found that
      regulation of trpP and pabA is unaltered in a rho mutant strain. Results from
      filter binding and gel mobility shift assays demonstrated that TRAP binds
      specifically to a segment of the trpP transcript that includes the untranslated
      leader and translation initiation region. While the affinities of TRAP for the
      trpP and pabA transcripts are similar, TRAP-mediated translation control of trpP
      is much more extensive than for pabA. RNA footprinting revealed that the trpP
      TRAP binding site consists of nine triplet repeats (five GAG, three UAG, and one
      AAG) that surround and overlap the trpP Shine-Dalgarno (S-D) sequence and
      translation start codon. Results from toeprint and RNA-directed cell-free
      translation experiments indicated that tryptophan-activated TRAP inhibits TrpP
      synthesis by preventing binding of a 30S ribosomal subunit. Taken together, our
      results establish that TRAP regulates translation of trpP by blocking ribosome
      binding. Thus, TRAP coordinately regulates tryptophan synthesis and transport by
      three distinct mechanisms: attenuation transcription of the trpEDCFBA operon,
      promoting formation of the trpE S-D blocking hairpin, and blocking ribosome
      binding to the pabA and trpP transcripts.

PMID- 14702296
TI  - The methyltransferase from the LlaDII restriction-modification system influences
      the level of expression of its own gene.
AB  - The type II restriction-modification (R-M) system LlaDII isolated from
      Lactococcus lactis contains two tandemly arranged genes, llaDIIR and llaDIIM,
      encoding a restriction endonuclease (REase) and a methyltransferase (MTase),
      respectively. Interestingly, two LlaDII recognition sites are present in the
      llaDIIM promoter region, suggesting that they may influence the activity of the
      promoter through methylation status. In this study, separate promoters for
      llaDIIR and llaDIIM were identified, and the regulation of the two genes at the
      transcriptional level was investigated. DNA fragments containing the putative
      promoters were cloned in a promoter probe vector and tested for activity in the
      presence and absence of the active MTase. The level of expression of the MTase
      was 5- to 10-fold higher than the level of expression of the REase. The results
      also showed that the presence of M.LlaDII reduced the in vivo expression of the
      llaDIIM promoter (P(llaDIIM)) up to 1,000-fold, whereas the activity of the
      llaDIIR promoter (P(llaDIIR)) was not affected. Based on site-specific mutations
      it was shown that both of the LlaDII recognition sites within P(llaDIIM) are
      required to obtain complete repression of transcriptional activity. No regulation
      was found for llaDIIR, which appears to be constitutively expressed.

PMID- 14702297
TI  - Osmoregulatory systems of Escherichia coli: identification of betaine-carnitine
      choline transporter family member BetU and distributions of betU and trkG among
      pathogenic and nonpathogenic isolates.
AB  - Multiple transporters mediate osmoregulatory solute accumulation in Escherichia
      coli K-12. The larger genomes of naturally occurring strains such as
      pyelonephritis isolates CFT073 and HU734 may encode additional osmoregulatory
      systems. CFT073 is more osmotolerant than HU734 in the absence of organic
      osmoprotectants, yet both strains grew in high osmolality medium at low K(+)
      (micromolar concentrations) and retained locus trkH, which encodes an
      osmoregulatory K(+) transporter. Both lacked the trkH homologue trkG.
      Transporters ProP and ProU account for all glycine-betaine uptake activity in E.
      coli K-12 and CFT073, but not in HU734, yet elimination of ProP and ProU impairs
      the growth of HU734, but not CFT073, in high osmolality human urine. No known
      osmoprotectant stimulated the growth of CFT073 in high osmolality minimal medium,
      but putative transporters YhjE, YiaMNO, and YehWXYZ may mediate uptake of
      additional osmoprotectants. Gene betU was isolated from HU734 by functional
      complementation and shown to encode a betaine uptake system that belongs to the
      betaine-choline-carnitine transporter family. The incidence of trkG and betU
      within the ECOR collection, representatives of the E. coli pathotypes (PATH), and
      additional strains associated with urinary tract infection (UTI) were determined.
      Gene trkG was present in 66% of the ECOR collection but only in 16% of the PATH
      and UTI collections. Gene betU was more frequently detected in ECOR groups B2 and
      D (50% of isolates) than in groups A, B1, and E (20%), but it was similar in
      overall incidence in the ECOR collection and in the combined UTI and PATH
      collections (32 and 34%, respectively). Genes trkG and betU may have been
      acquired by lateral gene transfer, since trkG is part of the rac prophage and
      betU is flanked by putative insertion sequences. Thus, BetU and TrkG contribute,
      with other systems, to the osmoregulatory capacity of the species E. coli, but
      they are not characteristic of a particular phylogenetic group or pathotype.

PMID- 14702298
TI  - atxA controls Bacillus anthracis capsule synthesis via acpA and a newly
      discovered regulator, acpB.
AB  - Two regulatory genes, acpA and atxA, have been reported to control expression of
      the Bacillus anthracis capsule biosynthesis operon capBCAD. The atxA gene is
      located on the virulence plasmid pXO1, while pXO2 carries acpA and the cap genes.
      acpA has been viewed as the major regulator of the cap operon because it is
      essential for capsule gene expression in a pXO1(-) pXO2(+) strain. atxA is
      essential for toxin gene transcription but has also been implicated in control of
      the cap genes. The molecular functions of the regulatory proteins are unknown. We
      examined cap gene expression in a genetically complete pXO1(+) pXO2(+) strain.
      Our results indicate that another pXO2 gene, acpB (previously called pXO2-53;
      accession no. NC002146.1:49418-50866), has a role in cap expression. The
      predicted amino acid sequence of AcpB is 62% similar to that of AcpA and 50%
      similar to that of AtxA. Assessment of cap gene transcription revealed that cap
      expression was not affected in a pXO1(+) pXO2(+) acpB-null mutant and was
      slightly reduced in an isogenic acpA mutant. However, cap gene expression was
      abolished in an acpA acpB double mutant. Microscopic examination of capsule
      synthesis by the mutants corroborated these findings. acpA and acpB expression is
      controlled by atxA; capsule synthesis and transcription of acpA and acpB were
      markedly reduced in an atxA mutant. The data suggest that, in a strain containing
      both virulence plasmids, atxA is the major regulator of capsule synthesis and
      controls capBCAD expression indirectly, via positive regulation of acpA and acpB.

PMID- 14702299
TI  - The alternative sigma factor sigmaB of Bacillus cereus: response to stress and
      role in heat adaptation.
AB  - A gene cluster encoding the alternative sigma factor sigma(B), three predicted
      regulators of sigma(B) (RsbV, RsbW, and RsbY), and one protein whose function is
      not known (Orf4) was identified in the genome sequence of the food pathogen
      Bacillus cereus ATCC 14579. Western blotting with polyclonal antibodies raised
      against sigma(B) revealed that there was 20.1-fold activation of sigma(B) after a
      heat shock from 30 to 42 degrees C. Osmotic upshock and ethanol exposure also
      upregulated sigma(B), albeit less than a heat shock. When the intracellular ATP
      concentration was decreased by exposure to carbonyl cyanide m
      chlorophenylhydrazone (CCCP), only limited increases in sigma(B) levels were
      observed, revealing that stress due to ATP depletion is not an important factor
      in sigma(B) activation in B. cereus. Analysis of transcription of the sigB operon
      by Northern blotting and primer extension revealed the presence of a sigma(B)
      dependent promoter upstream of the first open reading frame (rsbV) of the sigB
      operon, indicating that transcription of sigB is autoregulated. A second sigma(B)
      dependent promoter was identified upstream of the last open reading frame (orf4)
      of the sigB operon. Production of virulence factors and the nonhemolytic
      enterotoxin Nhe in a sigB null mutant was the same as in the parent strain.
      However, sigma(B) was found to play a role in the protective heat shock response
      of B. cereus. The sigB null mutant was less protected against the lethal
      temperature of 50 degrees C by a preadaptation to 42 degrees C than the parent
      strain was, resulting in a more-than-100-fold-reduced survival of the mutant
      after 40 min at 50 degrees C.

PMID- 14702300
TI  - Transcriptional regulation of the Staphylococcus aureus thioredoxin and
      thioredoxin reductase genes in response to oxygen and disulfide stress.
AB  - In this report we describe the cloning, organization, and promoter analysis of
      the Staphylococcus aureus thioredoxin (trxA) and thioredoxin reductase (trxB)
      genes and their transcription in response to changes in oxygen concentration and
      to oxidative stress compounds. Northern analysis showed that the S. aureus trxA
      and trxB genes were transcribed equally well in aerobic and anaerobic conditions.
      Several oxidative stress compounds were found to rapidly induce transcription of
      the trxA and trxB genes. The most pronounced effects were seen with diamide, a
      thiol-specific oxidant that promotes disulfide bond formation; menadione, a redox
      cycling agent; and tau-butyl hydroperoxide, an organic peroxide. In each case the
      induction was independent of the general stress sigma factor sigma(B). These
      studies show that the S. aureus trxA and trxB genes are upregulated following
      exposure to these oxidative stress agents, resulting in increased disulfide bond
      formation. In contrast, no effect of hydrogen peroxide on induction of the trxA
      and trxB genes was seen. We also show that the S. aureus thioredoxin reductase
      appears to be essential for growth. This observation, coupled with structural
      differences between the bacterial and mammalian thioredoxin reductases, suggests
      that it may serve as a target for the development of new antimicrobials.

PMID- 14702301
TI  - Translational coupling to an upstream gene promotes folding of the mycobacterial
      plasmid pAL5000 replication protein RepB and thereby its origin binding activity.
AB  - In the mycobacterial plasmid pAL5000 replication region, the replication genes
      repA and repB are organized in an operon. Earlier, a RepB-dependent origin
      binding activity was detected in Escherichia coli cells expressing the repA-repB
      operon. This activity was maximal when expression of the two genes was coupled
      (A. Basu, M. Chawla-Sarkar, S. Chakrabarti, and S. K. Das Gupta, J. Bacteriol.
      184:2204-2214, 2002). In this study we have shown that translational coupling
      makes a significant difference in the structure and function of RepB. When repB
      expression was coupled to repA, the polypeptide folded into an active structure
      (referred to as RepB*), which possessed higher helical content than RepB
      expressed independently. RepB* could also be distinguished from the less active
      RepB on the basis of sensitivity to OmpT, an outer membrane protease of E. coli:
      RepB* was sensitive to the protease, whereas RepB was resistant. Similar
      conformational differences between RepB* and RepB could be observed when repA was
      replaced with an unrelated gene, malE (encoding maltose binding protein). These
      results show that translational coupling of repB to an upstream gene is necessary
      for better folding and origin binding activity. It is speculated that in coupled
      systems where translation machinery is passed on from the upstream to the
      downstream open reading frame, cotranslational folding of the polypeptide
      expressed from the downstream open reading frame is enhanced due to increased
      folding competence of translationally primed ribosomes.

PMID- 14702302
TI  - Identification of the LIV-I/LS system as the third phenylalanine transporter in
      Escherichia coli K-12.
AB  - In Escherichia coli, the active transport of phenylalanine is considered to be
      performed by two different systems, AroP and PheP. However, a low level of
      accumulation of phenylalanine was observed in an aromatic amino acid transporter
      deficient E. coli strain (DeltaaroP DeltapheP Deltamtr Deltatna DeltatyrP). The
      uptake of phenylalanine by this strain was significantly inhibited in the
      presence of branched-chain amino acids. Genetic analysis and transport studies
      revealed that the LIV-I/LS system, which is a branched-chain amino acid
      transporter consisting of two periplasmic binding proteins, the LIV-binding
      protein (LIV-I system) and LS-binding protein (LS system), and membrane
      components, LivHMGF, is involved in phenylalanine accumulation in E. coli cells.
      The K(m) values for phenylalanine in the LIV-I and LS systems were determined to
      be 19 and 30 micro M, respectively. Competitive inhibition of phenylalanine
      uptake by isoleucine, leucine, and valine was observed for the LIV-I system and,
      surprisingly, also for the LS system, which has been assumed to be leucine
      specific on the basis of the results of binding studies with the purified LS
      binding protein. We found that the LS system is capable of transporting
      isoleucine and valine with affinity comparable to that for leucine and that the
      LIV-I system is able to transport tyrosine with affinity lower than that seen
      with other substrates. The physiological importance of the LIV-I/LS system for
      phenylalanine accumulation was revealed in the growth of phenylalanine
      auxotrophic E. coli strains under various conditions.

PMID- 14702303
TI  - Dihydropteridine reductase as an alternative to dihydrofolate reductase for
      synthesis of tetrahydrofolate in Thermus thermophilus.
AB  - A strategy devised to isolate a gene coding for a dihydrofolate reductase from
      Thermus thermophilus DNA delivered only clones harboring instead a gene (the T.
      thermophilus dehydrogenase [DH(Tt)] gene) coding for a dihydropteridine reductase
      which displays considerable dihydrofolate reductase activity (about 20% of the
      activity detected with 6,7-dimethyl-7,8-dihydropterine in the quinonoid form as a
      substrate). DH(Tt) appears to account for the synthesis of tetrahydrofolate in
      this bacterium, since a classical dihydrofolate reductase gene could not be found
      in the recently determined genome nucleotide sequence (A. Henne, personal
      communication). The derived amino acid sequence displays most of the highly
      conserved cofactor and active-site residues present in enzymes of the short-chain
      dehydrogenase/reductase family. The enzyme has no pteridine-independent
      oxidoreductase activity, in contrast to Escherichia coli dihydropteridine
      reductase, and thus appears more similar to mammalian dihydropteridine
      reductases, which do not contain a flavin prosthetic group. We suggest that
      bifunctional dihydropteridine reductases may be responsible for the synthesis of
      tetrahydrofolate in other bacteria, as well as archaea, that have been reported
      to lack a classical dihydrofolate reductase but for which possible substitutes
      have not yet been identified.

PMID- 14702304
TI  - Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter
      pylori-like gastric pathogen of cheetahs and other big cats.
AB  - Insights into bacterium-host interactions and genome evolution can emerge from
      comparisons among related species. Here we studied Helicobacter acinonychis
      (formerly H. acinonyx), a species closely related to the human gastric pathogen
      Helicobacter pylori. Two groups of strains were identified by randomly amplified
      polymorphic DNA fingerprinting and gene sequencing: one group from six cheetahs
      in a U.S. zoo and two lions in a European circus, and the other group from a
      tiger and a lion-tiger hybrid in the same circus. PCR and DNA sequencing showed
      that each strain lacked the cag pathogenicity island and contained a degenerate
      vacuolating cytotoxin (vacA) gene. Analyses of nine other genes (glmM, recA,
      hp519, glr, cysS, ppa, flaB, flaA, and atpA) revealed a approximately 2% base
      substitution difference, on average, between the two H. acinonychis groups and a
      approximately 8% difference between these genes and their homologs in H. pylori
      reference strains such as 26695. H. acinonychis derivatives that could
      chronically infect mice were selected and were found to be capable of persistent
      mixed infection with certain H. pylori strains. Several variants, due variously
      to recombination or new mutation, were found after 2 months of mixed infection.
      H. acinonychis ' modest genetic distance from H. pylori, its ability to infect
      mice, and its ability to coexist and recombine with certain H. pylori strains in
      vivo should be useful in studies of Helicobacter infection and virulence
      mechanisms and studies of genome evolution.

PMID- 14702305
TI  - Phage shock protein PspA of Escherichia coli relieves saturation of protein
      export via the Tat pathway.
AB  - Overexpression of either heterologous or homologous proteins that are routed to
      the periplasm via the twin-arginine translocation (Tat) pathway results in a
      block of export and concomitant accumulation of the respective protein precursor
      in the cytoplasm. Screening of a plasmid-encoded genomic library for mutants that
      confer enhanced export of a TorA signal sequence (ssTorA)-GFP-SsrA fusion
      protein, and thus result in higher cell fluorescence, yielded the pspA gene
      encoding phage shock protein A. Coexpression of pspA relieved the secretion block
      observed with ssTorA-GFP-SsrA or upon overexpression of the native Tat proteins
      SufI and CueO. A similar effect was observed with the Synechocystis sp. strain
      PCC6803 PspA homologue, VIPP1, indicating that the role of PspA in Tat export may
      be phylogenetically conserved. Mutations in Tat components that completely
      abolish export result in a marked induction of PspA protein synthesis, consistent
      with its proposed role in enhancing protein translocation via Tat.

PMID- 14702306
TI  - Participation of fad and mbt genes in synthesis of mycobactin in Mycobacterium
      smegmatis.
AB  - Colonies of Mycobacterium smegmatis LR222 on iron-limiting (0.1 micro M Fe)
      minimal medium agar fluoresce under UV light due to the accumulation in the cells
      of the deferri form of the siderophore mycobactin. Two mutants with little or no
      fluorescence, designated LUN8 and LUN9, were isolated by screening colonies of
      transposon (Tn611)-mutagenized M. smegmatis. Ferrimycobactin prepared from iron
      restricted cells of the wild type had an R(f) of 0.62 on high-performance thin
      layer chromatography (HPTLC) and a characteristic visible absorption spectrum
      with a peak near 450 nm. Similar extracts from LUN8 cells contained a small
      amount of ferrimycobactin with an R(f) of 0.58 on HPTLC and an absorption
      spectrum with the peak shifted to a wavelength lower than that of the wild-type
      ferrimycobactin. Nuclear magnetic resonance spectroscopy studies suggested that
      the LUN8 mycobactin may have an altered fatty acid side chain. Mutant strain LUN9
      produced no detectable mycobactin. Neither mutant strain produced measurable
      amounts of excreted mycobactin, although both excreted exochelin (the
      mycobacterial peptido-hydroxamate siderophore), and both mutants were more
      sensitive than the wild-type strain to growth inhibition by the iron chelator
      ethylenediamine-di(o-hydroxyphenylacetic acid). The transposon insertion sites
      were identified, and sequence analyses of the cloned flanking chromosome regions
      showed that the mutated gene in LUN9 was an orthologue of the Mycobacterium
      tuberculosis mycobactin biosynthetic gene mbtE. The mutated gene in LUN8 had
      homology with M. tuberculosis fadD33 (Rv1345), a gene that may encode an acyl
      coenzyme A synthase and which previously was not known to participate in
      synthesis of mycobactin.

PMID- 14702307
TI  - Structural and genetic characterization of the Shigella boydii type 13 O antigen.
AB  - Shigella is an important human pathogen. It is generally agreed that Shigella and
      Escherichia coli constitute a single species; the only exception is Shigella
      boydii type 13, which is more distantly related to E. coli and other Shigella
      forms and seems to represent another species. This gives S. boydii type 13 an
      important status in evolution. O antigen is the polysaccharide part of the
      lipopolysaccharide in the outer membrane of gram-negative bacteria and plays an
      important role in pathogenicity. The chemical structure and genetic organization
      of the S. boydii type 13 O antigen were investigated. The O polysaccharide was
      found to be acid labile owing to the presence of a glycosyl phosphate linkage in
      the main chain. The structure of the linear pentasaccharide phosphate repeating
      unit (O unit) was established by nuclear magnetic resonance spectroscopy,
      including two-dimensional COSY, TOCSY, ROESY, and H-detected 1H, 13C and 1H, 31P
      HMQC experiments, along with chemical methods. The O antigen gene cluster of S.
      boydii type 13 was located and sequenced. Genes for synthesis of UDP-2-acetamido
      2,6-dideoxy-L-glucose and genes that encode putative sugar transferases, O unit
      flippase, and O antigen polymerase were identified. Seven genes were found to be
      specific to S. boydii type 13. The S. boydii type 13 O antigen gene cluster has
      higher levels of sequence similarity with Vibrio cholerae gene clusters and may
      be evolutionarily related to these gene clusters.

PMID- 14702308
TI  - The BH1999 protein of Bacillus halodurans C-125 is gentisyl-coenzyme A
      thioesterase.
AB  - In this study, we have shown that recombinant BH1999 from Bacillus halodurans
      catalyzes the hydrolysis of gentisyl coenzyme A (CoA) (2,5-dihydroxybenzoyl
      coenzyme A) at physiological pH with a k(cat)/K(m) of 1.6 x 10(6) M(-1) s(-1) and
      the hydrolysis of 3-hydroxybenzoyl-CoA with a k(cat)/K(m) of 3.0 x 10(5) M(-1) s(
      1). All other acyl-CoA thioesters tested had low or no substrate activity. The
      BH1999 gene is juxtaposed with a gene cluster that contains genes believed to
      function in gentisate oxidative degradation. It is hypothesized that BH1999
      functions as a gentisyl-CoA thioesterase. Gentisyl-CoA thioesterase shares the
      backbone fold and the use of an active site aspartate residue to mediate
      catalysis with the 4-hydroxybenzoyl-CoA thioesterase of the hotdog fold enzyme
      superfamily. A comparative study of these two enzymes showed that they differ
      greatly in the rate contribution made by the catalytic aspartate, in the pH
      dependence of catalysis, and in substrate specificity.

PMID- 14702309
TI  - Complete sequence and evolutionary genomic analysis of the Pseudomonas aeruginosa
      transposable bacteriophage D3112.
AB  - Bacteriophage D3112 represents one of two distinct groups of transposable phage
      found in the clinically relevant, opportunistic pathogen Pseudomonas aeruginosa.
      To further our understanding of transposable phage in P. aeruginosa, we have
      sequenced the complete genome of D3112. The genome is 37,611 bp, with an overall
      G+C content of 65%. We have identified 53 potential open reading frames,
      including three genes (the c repressor gene and early genes A and B) that have
      been previously characterized and sequenced. The organization of the putative
      coding regions corresponds to published genetic and transcriptional maps and is
      very similar to that of enterobacteriophage Mu. In contrast, the International
      Committee on Taxonomy of Viruses has classified D3112 as a lambda-like phage on
      the basis of its morphology. Similarity-based analyses identified 27 open reading
      frames with significant matches to proteins in the NCBI databases. Forty-eight
      percent of these were similar to Mu-like phage and prophage sequences, including
      proteins responsible for transposition, transcriptional regulation, virion
      morphogenesis, and capsid formation. The tail proteins were highly similar to
      prophage sequences in Escherichia coli and phage Phi12 from Staphylococcus
      aureus, while proteins at the right end were highly similar to proteins in
      Xylella fastidiosa. We performed phylogenetic analyses to understand the
      evolutionary relationships of D3112 with respect to Mu-like versus lambda-like
      bacteriophages. Different results were obtained from similarity-based versus
      phylogenetic analyses in some instances. Overall, our findings reveal a highly
      mosaic structure and suggest that extensive horizontal exchange of genetic
      material played an important role in the evolution of D3112.

PMID- 14702310
TI  - Molecular and functional characterization of a unique sucrose hydrolase from
      Xanthomonas axonopodis pv. glycines.
AB  - A novel sucrose hydrolase (SUH) from Xanthomonas axonopodis pv. glycines, a
      causative agent of bacterial pustule disease on soybeans, was studied at the
      functional and molecular levels. SUH was shown to act rather specifically on
      sucrose (K(m) = 2.5 mM) but not on sucrose-6-phosphate. Protein analysis of
      purified SUH revealed that, in this monomeric enzyme with an estimated molecular
      mass of 70,223 +/- 12 Da, amino acid sequences determined for several segments
      have corresponding nucleotide sequences in XAC3490, a protein-coding gene found
      in the genome of X. axonopodis pv. citri. Based on this information, the SUH
      gene, consisting of an open reading frame of 1,935 bp, was cloned by screening a
      genomic library of X. axonopodis pv. glycines 8ra. Database searches and sequence
      comparison revealed that SUH has significant homology to some family 13 enzymes,
      with all of the crucial invariant residues involved in the catalytic mechanism
      conserved, but it shows no similarity to known invertases belonging to family 32.
      suh expression in X. axonopodis pv. glycines requires sucrose induction, and
      insertional mutagenesis resulted in an absence of sucrose-inducible sucrose
      hydrolase activity in crude protein extracts and a sucrose-negative phenotype.
      Recombinant SUH, overproduced in Escherichia coli and purified, was shown to have
      the same enzymatic characteristics in terms of kinetic parameters.

PMID- 14702311
TI  - Identification of NAD+ synthetase from Streptococcus sobrinus as a B-cell
      stimulatory protein.
AB  - Streptococcus sobrinus, one agent of dental caries, secretes a protein that
      induces lymphocyte polyclonal activation of the host as a mechanism of immune
      evasion. We have isolated from culture supernatants of this bacterium a protein
      with murine B-cell-stimulatory properties and subsequently cloned the relevant
      gene. It contains an open reading frame of 825 bp encoding a polypeptide with 275
      amino acid residues and a molecular mass of 30 kDa. The protein displays high
      sequence homology with NAD(+) synthetases from several organisms, including a
      conserved fingerprint sequence (SGGXD) characteristic of ATP pyrophosphatases.
      The polypeptide was expressed in Escherichia coli as a hexahistidine-tagged
      protein and purified in an enzymatically active form. The recombinant NAD(+)
      synthetase stimulates murine B cells after in vitro treatment of spleen cell
      cultures, as demonstrated by its ability to induce up-regulation of the
      expression of CD69, an early marker of lymphocyte activation. Stimulation with
      the recombinant NAD(+) synthetase was also observed with other B-cell markers,
      such as CD19(+), B220(+), and CD21(+). Cell proliferation follows the activation
      induced by the recombinant NAD(+) synthetase.

PMID- 14702312
TI  - Occurrence and characterization of mercury resistance in the hyperthermophilic
      archaeon Sulfolobus solfataricus by use of gene disruption.
AB  - Mercury resistance mediated by mercuric reductase (MerA) is widespread among
      bacteria and operates under the control of MerR. MerR represents a unique class
      of transcription factors that exert both positive and negative regulation on gene
      expression. Archaea and bacteria are prokaryotes, yet little is known about the
      biological role of mercury in archaea or whether a resistance mechanism occurs in
      these organisms. The archaeon Sulfolobus solfataricus was sensitive to mercuric
      chloride, and low-level adaptive resistance could be induced by metal
      preconditioning. Protein phylogenetic analysis of open reading frames SSO2689 and
      SSO2688 clarified their identity as orthologs of MerA and MerR. Northern analysis
      established that merA transcription responded to mercury challenge, since mRNA
      levels were transiently induced and, when normalized to 7S RNA, approximated
      values for other highly expressed transcripts. Primer extension analysis of merA
      mRNA predicted a noncanonical TATA box with nonstandard transcription start site
      spacing. The functional roles of merA and merR were clarified further by gene
      disruption. The merA mutant exhibited mercury sensitivity relative to wild type
      and was defective in elemental mercury volatilization, while the merR mutant was
      mercury resistant. Northern analysis of the merR mutant revealed merA
      transcription was constitutive and that transcript abundance was at maximum
      levels. These findings constitute the first report of an archaeal heavy metal
      resistance system; however, unlike bacteria the level of resistance is much
      lower. The archaeal system employs a divergent MerR protein that acts only as a
      negative transcriptional regulator of merA expression.

PMID- 14702313
TI  - A multicomponent system is required for tetracycline-induced excision of Tn4555.
AB  - Bacteroides spp. are the predominant organisms in the intestinal tract, and they
      also are important opportunistic pathogens. Antibiotic therapy of Bacteroides
      infections often is complicated by the prevalence of drug-resistant organisms
      which acquire resistance genes from a variety of mobile genetic elements
      including conjugative transposons (CTns) and mobilizable transposons (MTns).
      Tn4555 is an MTn that encodes beta-lactam resistance, and it is efficiently
      mobilized by the Bacteroides CTns via a tetracycline (TET)-inducible mechanism.
      In this study a model system with CTn341 and a Tn4555 minielement was used to
      examine Tn4555 excision from the chromosome. Using PCR and mobilization assays it
      was established that excision was stimulated by TET in the presence of CTn341. In
      order to determine which Tn4555 genes were required for excision, int, tnpA,
      tnpC, xis, and mobA mutants were examined. The results indicated that int plus
      two additional genes, tnpC and xis, were required for optimal excision. In
      addition, there was no requirement for the mobA gene, as had been shown for
      another MTn, NBU1. The Xis protein sequence is related to a family of plasmid
      excisionases, but the TnpC gene product did not match anything in the sequence
      databases. Evidence also was obtained that suggested that Xis is involved in the
      control of TET-induced excision and in control of mobilization by CTn341.
      Overall, these results indicate that excision of MTns is a complex process that
      requires multiple gene products.

PMID- 14702314
TI  - The HWE histidine kinases, a new family of bacterial two-component sensor kinases
      with potentially diverse roles in environmental signaling.
AB  - Two-component signal transduction pathways play a major role in the response of
      bacteria to external cues. These pathways are initiated by large collection of
      histidine kinases (HKs) containing a sensor domain that perceives the
      environmental signal followed by an HK domain that triggers a histidine-aspartate
      phosphorelay. Previous phylogenetic analyses identified 11 major families of two
      component HKs by comparing signature motifs within the HK domain. Here we
      describe a new family with homology to Agrobacterium tumefaciens BphP2, an HK
      first discovered by the presence of a phytochrome sensor domain involved in light
      perception. Members of this sensor HK family differ from most others by the
      absence of a recognizable F box and the presence of several uniquely conserved
      residues, including a histidine in the N box and a tryptophan-X-glutamic acid
      sequence in the G1 box, which we have used to define the family (HWE). At least
      81 members were identified in a variety of alpha- and gamma-proteobacteria, with
      a significant enrichment in the Rhizobiaceae family. Several representatives were
      shown to have HK activity in vitro, supporting their proposed participation in
      phosphorelays. One or more domains related to signal transduction were evident N
      terminal to the HK domain, including chemotactic methyltransferase domains,
      suggesting that this family has multiple roles in environmental signaling. The
      discovery of the HWE family further extends the diversity within the HK
      superfamily and expands the importance of two-component signaling in bacteria.

PMID- 14702315
TI  - The acnD genes of Shewenella oneidensis and Vibrio cholerae encode a new Fe/S
      dependent 2-methylcitrate dehydratase enzyme that requires prpF function in vivo.
AB  - The propionate utilization operons of several bacteria differ from each other in
      the occurrence of two genes, acnD and prpF, in place of or in addition to the
      prpD gene encoding an Fe/S-independent 2-methylcitrate dehydratase enzyme. We
      cloned the acnD and prpF genes from two organisms, Shewanella oneidensis and
      Vibrio cholerae, and found that, together, the AcnD and PrpF proteins restored
      the ability of a prpD mutant strain of Salmonella enterica to grow on propionate
      as a source of carbon and energy. However, neither acnD nor prpF alone was able
      to substitute for prpD. The AcnD and PrpF proteins were isolated and
      biochemically analyzed. The AcnD protein required reconstitution of an Fe/S
      cluster for activity. All detectable AcnD activity was lost after incubation with
      iron-chelating agents, and no AcnD activity was observed after attempted
      reconstitution without iron. Nuclear magnetic resonance spectroscopy and in vitro
      activity assay data showed that AcnD dehydrated 2-methylcitrate and citrate to 2
      methyl-cis-aconitate and cis-aconitate, respectively; AcnD also hydrated cis
      aconitate. However, 2-methylisocitrate and isocitrate were not substrates for
      AcnD, indicating that AcnD only catalyzes the first half of the aconitase-like
      dehydration reactions. No aconitase-like activity was found for PrpF. It is
      hypothesized that, in vivo, PrpF is an accessory protein required to prevent
      oxidative damage of the Fe/S center of active AcnD enzyme or that it may be
      involved in synthesis or repair of the Fe/S cluster present in AcnD.

PMID- 14702316
TI  - A phosphoprotein from the archaeon Sulfolobus solfataricus with protein
      serine/threonine kinase activity.
AB  - Sulfolobus solfataricus contains a membrane-associated protein kinase activity
      that displays a strong preference for threonine as the phospho-acceptor amino
      acid residue. When a partially purified detergent extract of the membrane
      fraction from the archaeon S. solfataricus that had been enriched for this
      activity was incubated with [gamma-(32)P]ATP, radiolabeled phosphate was
      incorporated into roughly a dozen polypeptides, several of which contained
      phosphothreonine. One of the phosphothreonine-containing proteins was identified
      by mass peptide profiling as the product of open reading frame [ORF] sso0469.
      Inspection of the DNA-derived amino acid sequence of the predicted protein
      product of ORF sso0469 revealed the presence of sequence characteristics faintly
      reminiscent of the "eukaryotic" protein kinase superfamily. ORF sso0469 therefore
      was cloned, and its polypeptide product was expressed in Escherichia coli. The
      recombinant protein formed insoluble aggregates that could be dispersed using
      urea or detergents. The solubilized polypeptide phosphorylated several exogenous
      proteins in vitro, including casein, myelin basic protein, and bovine serum
      albumin. Mutagenic alteration of amino acids predicted to be essential for
      catalytic activity abolished or severely reduced catalytic activity.
      Phosphorylation of exogenous substrates took place on serine and, occasionally,
      threonine. This new archaeal protein kinase displayed no catalytic activity when
      GTP was substituted for ATP as the phospho-donor substrate, while Mn(2+) was the
      preferred cofactor.

PMID- 14702317
TI  - The sorbitol phosphotransferase system is responsible for transport of 2-C-methyl
      D-erythritol into Salmonella enterica serovar typhimurium.
AB  - 2-C-methyl-D-erythritol 4-phosphate is the first committed intermediate in the
      biosynthesis of the isoprenoid precursors isopentenyl diphosphate and
      dimethylallyl diphosphate. Supplementation of the growth medium with 2-C-methyl-D
      erythritol has been shown to complement disruptions in the Escherichia coli gene
      for 1-deoxy-D-xylulose 5-phosphate synthase, the enzyme that synthesizes the
      immediate precursor of 2-C-methyl-D-erythritol 4-phosphate. In order to be
      utilized in isoprenoid biosynthesis, 2-C-methyl-D-erythritol must be
      phosphorylated. We describe the construction of Salmonella enterica serovar
      Typhimurium strain RMC26, in which the essential gene encoding 1-deoxy-D-xylulose
      5-phosphate synthase has been disrupted by insertion of a synthetic mevalonate
      operon consisting of the yeast ERG8, ERG12, and ERG19 genes, responsible for
      converting mevalonate to isopentenyl diphosphate under the control of an
      arabinose-inducible promoter. Random mutagenesis of RMC26 produced defects in the
      sorbitol phosphotransferase system that prevented the transport of 2-C-methyl-D
      erythritol into the cell. RMC26 and mutant strains of RMC26 unable to grow on 2-C
      methyl-D-erythritol were incubated in buffer containing mevalonate and deuterium
      labeled 2-C-methyl-D-erythritol. Ubiquinone-8 was isolated from these cells and
      analyzed for deuterium content. Efficient incorporation of deuterium was observed
      for RMC26. However, there was no evidence of deuterium incorporation into the
      isoprenoid side chain of ubiquinone Q8 in the RMC26 mutants.

PMID- 14702318
TI  - The Caulobacter crescentus CgtAC protein cosediments with the free 50S ribosomal
      subunit.
AB  - The Obg family of GTPases is widely conserved and predicted to play an as-yet
      unknown role in translation. Recent reports provide circumstantial evidence that
      both eukaryotic and prokaryotic Obg proteins are associated with the large
      ribosomal subunit. Here we provide direct evidence that the Caulobacter
      crescentus CgtA(C) protein is associated with the free large (50S) ribosomal
      subunit but not with 70S monosomes or with translating ribosomes. In contrast to
      the Bacillus subtilis and Escherichia coli proteins, CgtA(C) does not fractionate
      in a large complex by gel filtration, indicating a moderately weak association
      with the 50S subunit. Moreover, binding of CgtA(C) to the 50S particle is
      sensitive to salt concentration and buffer composition but not guanine nucleotide
      occupancy of CgtA(C). Assays of epitope-tagged wild-type and mutant variants of
      CgtA(C) indicate that the C terminus of CgtA(C) is critical for 50S association.
      Interestingly, the addition of a C-terminal epitope tag also affected the ability
      of various cgtA(C) alleles to function in vivo. Depletion of CgtA(C) led to
      perturbations in the polysome profile, raising the possibility that CgtA(C) is
      involved in ribosome assembly or stability.

PMID- 14702319
TI  - Genetic analysis of the cell division protein FtsI (PBP3): amino acid
      substitutions that impair septal localization of FtsI and recruitment of FtsN.
AB  - FtsI (also called PBP3) of Escherichia coli is a transpeptidase required for
      synthesis of peptidoglycan in the division septum and is one of several proteins
      that localize to the septal ring. FtsI comprises a small cytoplasmic domain, a
      transmembrane helix, a noncatalytic domain of unknown function, and a catalytic
      (transpeptidase) domain. The last two domains reside in the periplasm. We used
      PCR to randomly mutagenize ftsI, ligated the products into a green fluorescent
      protein fusion vector, and screened approximately 7,500 transformants for gfp
      ftsI alleles that failed to complement an ftsI null mutant. Western blotting and
      penicillin-binding assays were then used to weed out proteins that were unstable,
      failed to insert into the cytoplasmic membrane, or were defective in catalysis.
      The remaining candidates were tested for septal localization and ability to
      recruit another division protein, FtsN, to the septal ring. Mutant proteins
      severely defective in localization to the septal ring all had lesions in one of
      three amino acids-R23, L39, or Q46-that are in or near the transmembrane helix
      and implicate this region of FtsI in septal localization. Mutant FtsI proteins
      defective in recruitment of FtsN all had lesions in one of eight residues in the
      noncatalytic domain. The most interesting of these mutants had lesions at G57,
      S61, L62, or R210. Although separated by approximately 150 residues in the
      primary sequence, these amino acids are close together in the folded protein and
      might constitute a site of FtsI-FtsN interaction.

PMID- 14702320
TI  - The genome-sequenced variant of Campylobacter jejuni NCTC 11168 and the original
      clonal clinical isolate differ markedly in colonization, gene expression, and
      virulence-associated phenotypes.
AB  - The genome sequence of the enteric bacterial pathogen Campylobacter jejuni NCTC
      11168 (11168-GS) was published in 2000, providing a valuable resource for the
      identification of C. jejuni-specific colonization and virulence factors.
      Surprisingly, the 11168-GS clone was subsequently found to colonize 1-day-old
      chicks following oral challenge very poorly compared to other strains. In
      contrast, we have found that the original clinical isolate from which 11168-GS
      was derived, 11168-O, is an excellent colonizer of chicks. Other marked
      phenotypic differences were also identified: 11168-O invaded and translocated
      through tissue culture cells far more efficiently and rapidly than 11168-GS, was
      significantly more motile, and displayed a different morphology. Serotyping,
      multiple high-resolution molecular genotyping procedures, and subtractive
      hybridization did not yield observable genetic differences between the variants,
      suggesting that they are clonal. However, microarray transcriptional profiling of
      these strains under microaerobic and severely oxygen-limited conditions revealed
      dramatic expression differences for several gene families. Many of the
      differences were in respiration and metabolism genes and operons, suggesting that
      adaptation to different oxygen tensions may influence colonization potential.
      This correlates biologically with our observation that anaerobically priming
      11168-GS or aerobically passaging 11168-O caused an increase or decrease,
      respectively, in colonization compared to the parent strain. Expression
      differences were also observed for several flagellar genes and other less well
      characterized genes that may participate in motility. Targeted sequencing of the
      sigma factors revealed specific DNA differences undetected by the other genomic
      methods [corrected].

PMID- 14702321
TI  - Sequence analysis of the mobile genome island pKLC102 of Pseudomonas aeruginosa
      C.
AB  - The Pseudomonas aeruginosa plasmid pKLC102 coexists as a plasmid and a genome
      island in clone C strains. Whereas the related plasmid pKLK106 reversibly
      recombines with P. aeruginosa clone K chromosomes at one of the two tRNA(Lys)
      genes, pKLC102 is incorporated into the tRNA(Lys) gene only close to the pilA
      locus. Targeting of the other tRNA(Lys) copy in the chromosome is blocked by a
      23,395-bp mosaic of truncated PAO open reading frames, transposons, and pKLC102
      homologs. Annotation and phylogenetic analysis of the large 103,532-bp pKLC102
      sequence revealed that pKLC102 is a hybrid of plasmid and phage origin. The
      plasmid lineage conferred oriV and genes for replication, partitioning, and
      conjugation, including a pil cluster encoding type IV thin sex pili and an 8,524
      bp chvB glucan synthetase gene that is known to be a major determinant for host
      tropism and virulence. The phage lineage conferred integrase, att, and a syntenic
      set of conserved hypothetical genes also observed in the tRNA(Gly)-associated
      genome islands of P. aeruginosa clone C chromosomes. In subgroup C isolates from
      patients with cystic fibrosis, pKLC102 was irreversibly fixed into the chromosome
      by the insertion of the large 23,061-bp class I transposon TNCP23, which is a
      composite of plasmid, integron, and IS6100 elements. Intramolecular transposition
      of a copy of IS6100 led to chromosomal inversions and disruption of plasmid
      synteny. The case of pKLC102 in P. aeruginosa clone C documents the intraclonal
      evolution of a genome island from a mobile ancestor via a reversibly integrated
      state to irreversible incorporation and dissipation in the chromosome.

PMID- 14702322
TI  - An evolutionary hot spot: the pNGR234b replicon of Rhizobium sp. strain NGR234.
AB  - Rhizobium sp. strain NGR234 has an exceptionally broad host range and is able to
      nodulate more than 112 genera of legumes. Since the overall organization of the
      NGR234 genome is strikingly similar to that of the narrow-host-range symbiont
      Rhizobium meliloti strain 1021 (also known as Sinorhizobium meliloti), the
      obvious question is why are the spectra of hosts so different? Study of the early
      symbiotic genes of both bacteria (carried by the SymA plasmids) did not provide
      obvious answers. Yet, both rhizobia also possess second megaplasmids that bear,
      among many other genes, those that are involved in the synthesis of extracellular
      polysaccharides (EPSs). EPSs are involved in fine-tuning symbiotic interactions
      and thus may help answer the broad- versus narrow-host-range question.
      Accordingly, we sequenced two fragments (total, 594 kb) that encode 575 open
      reading frames (ORFs). Comparisons revealed 19 conserved gene clusters with high
      similarity to R. meliloti, suggesting that a minimum of 28% (158 ORFs) of the
      genetic information may have been acquired from a common ancestor. The largest
      conserved cluster carried the exo and exs genes and contained 31 ORFs. In
      addition, nine highly conserved regions with high similarity to Agrobacterium
      tumefaciens C58, Bradyrhizobium japonicum USDA110, and Mesorhizobium loti strain
      MAFF303099, as well as two conserved clusters that are highly homologous to
      similar regions in the plant pathogen Erwinia carotovora, were identified.
      Altogether, these findings suggest that >/==" BORDER="0">40% of the pNGR234b
      genes are not strain specific and were probably acquired from a wide variety of
      other microbes. The presence of 26 ORFs coding for transposases and site-specific
      integrases supports this contention. Surprisingly, several genes involved in the
      degradation of aromatic carbon sources and genes coding for a type IV pilus were
      also found.

PMID- 14702323
TI  - Pseudomonas syringae type III secretion system targeting signals and novel
      effectors studied with a Cya translocation reporter.
AB  - Pseudomonas syringae pv. tomato strain DC3000 is a pathogen of tomato and
      Arabidopsis: The hrp-hrc-encoded type III secretion system (TTSS), which injects
      bacterial effector proteins (primarily called Hop or Avr proteins) into plant
      cells, is required for pathogenicity. In addition to being regulated by the HrpL
      alternative sigma factor, most avr or hop genes encode proteins with N termini
      that have several characteristic features, including (i) a high percentage of Ser
      residues, (ii) an aliphatic amino acid (Ile, Leu, or Val) or Pro at the third or
      fourth position, and (iii) a lack of negatively charged amino acids within the
      first 12 residues. Here, the well-studied effector AvrPto was used to optimize a
      calmodulin-dependent adenylate cyclase (Cya) reporter system for Hrp-mediated
      translocation of P. syringae TTSS effectors into plant cells. This system
      includes a cloned P. syringae hrp gene cluster and the model plant Nicotiana
      benthamiana. Analyses of truncated AvrPto proteins fused to Cya revealed that the
      N-terminal 16 amino acids and/or codons of AvrPto are sufficient to direct weak
      translocation into plant cells and that longer N-terminal fragments direct
      progressively stronger translocation. AvrB, tested because it is poorly secreted
      in cultures by the P. syringae Hrp system, was translocated into plant cells as
      effectively as AvrPto. The translocation of several DC3000 candidate Hop proteins
      was also examined by using Cya as a reporter, which led to identification of
      three new intact Hop proteins, designated HopPtoQ, HopPtoT1, and HopPtoV, as well
      as two truncated Hop proteins encoded by the naturally disrupted genes
      hopPtoS4::tnpA and hopPtoAG::tnpA. We also confirmed that HopPtoK, HopPtoC, and
      AvrPphE(Pto) are translocated into plant cells. These results increased the
      number of Hrp system-secreted proteins in DC3000 to 40. Although most of the
      newly identified Hop proteins possess N termini that have the same features as
      the N termini of previously described Hop proteins, HopPtoV has none of these
      characteristics. Our results indicate that Cya should be a useful reporter for
      exploring multiple aspects of the Hrp system in P. syringae.

PMID- 14702324
TI  - Comparative genomics of Rickettsia prowazekii Madrid E and Breinl strains.
AB  - Rickettsia prowazekii, the causative agent of epidemic typhus, has been
      responsible for millions of human deaths. Madrid E is an attenuated strain of R.
      prowazekii, while Breinl is a virulent strain. The genomic DNA sequence of Madrid
      E has recently been published. To study the genomic variations between Madrid E
      (reference) and Breinl (test) DNAs, cohybridization experiments were performed on
      a DNA microarray containing all 834 protein-coding genes of Madrid E. Of the 834
      genes assessed, 24 genes showed 1.5- to 2.0-fold increases in hybridization
      signals in Breinl DNA compared to Madrid E DNA, indicating the presence of
      genomic variations in approximately 3% of the total genes. Eighteen of these 24
      genes are predicted to be involved in different functions. Southern blot analysis
      of five genes, virB4, ftsK, rfbE, lpxA, and rpoH, suggested the presence of an
      additional paralog(s) in Breinl, which might be related to the observed increase
      in hybridization signals. Studies by real-time reverse transcription-PCR revealed
      an increase in expression of the above-mentioned five genes and five other genes.
      In addition to the elevated hybridization signals of 24 genes observed in the
      Breinl strain, one gene (rp084) showed only 1/10 the hybridization signal of
      Madrid E. Further analysis of this gene by PCR and sequencing revealed a large
      deletion flanking the whole rp084 gene and part of the rp083 gene in the virulent
      Breinl strain. The results of this first rickettsial DNA microarray may provide
      some important information for the elucidation of pathogenic mechanisms of R.
      prowazekii.

PMID- 14702325
TI  - Surface layer protein EA1 is not a component of Bacillus anthracis spores but is
      a persistent contaminant in spore preparations.
AB  - EA1 is an abundant, highly antigenic, surface layer protein of Bacillus anthracis
      vegetative cells. Recent studies indicate that EA1 is also a component of B.
      anthracis spores and a potential marker for spore detection. We show here that
      EA1 is not a spore component but a persistent contaminant in spore preparations.

PMID- 14702326
TI  - Cloning and characterization of acetohydroxyacid synthase from Bacillus
      stearothermophilus.
AB  - Five genes from the ilv-leu operon from Bacillus stearothermophilus have been
      sequenced. Acetohydroxyacid synthase (AHAS) and its subunits were separately
      cloned, purified, and characterized. This thermophilic enzyme resembles AHAS III
      of Escherichia coli, and regulatory subunits of AHAS III complement the catalytic
      subunit of the AHAS of B. stearothermophilus, suggesting that AHAS III is
      functionally and evolutionally related to the single AHAS of gram-positive
      bacteria.

PMID- 14702327
TI  - PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates
      resistance to cationic antimicrobial peptides and addition of aminoarabinose to
      lipid A.
AB  - Spontaneous polymyxin-resistant mutants of Pseudomonas aeruginosa were isolated.
      The mutations responsible for this phenotype were mapped to a two-component
      signal transduction system similar to PmrAB of Salmonella enterica serovar
      Typhimurium. Lipid A of these mutants contained aminoarabinose, an inducible
      modification that is associated with polymyxin resistance. Thus, P. aeruginosa
      possesses a mechanism that induces resistance to cationic antimicrobial peptides
      in response to environmental conditions.

PMID- 14702328
TI  - Expression and regulation of a silent operon, hyf, coding for hydrogenase 4
      isoenzyme in Escherichia coli.
AB  - On the basis of hyf-lacZ fusion studies, the hyf operon of Escherichia coli,
      noted for encoding the fourth hydrogenase isoenzyme (HYD4), is not expressed at a
      significant level in a wild-type strain. However, mutant FhlA proteins
      (constitutive activators of the hyc-encoded hydrogenase 3 isoenzyme) activated
      hyf-lacZ. HyfR, an FhlA homolog encoded by the hyfR gene present at the end of
      the hyf operon, also activated transcription of hyf-lacZ but did so only when
      hyfR was expressed from a heterologous promoter. The HYD4 isoenzyme did not
      substitute for HYD3 in H(2) production. Optimum expression of hyf-lacZ required
      the presence of cyclic AMP receptor protein-cyclic AMP complex and anaerobic
      conditions when HyfR was the activator.

PMID- 14702329
TI  - Biphasic excitation by leucine in Escherichia coli chemotaxis.
AB  - Leucine concentration jumps (applied by photolysis of inert derivatives)
      triggered swim or tumble responses in Escherichia coli mutants lacking Tsr or
      Tar, respectively. Wild-type E. coli bacteria were attracted in spatial assays
      when the initial leucine concentration difference was 5 to 120 micro M but were
      repulsed when it was over 0.5 mM. Their responses to concentration jumps
      confirmed earlier deductions regarding biphasic excitation.

PMID- 14702331
TI  - Modeling interactions between electrical activity and second-messenger cascades
      in Aplysia neuron R15.
AB  - The biophysical properties of neuron R15 in Aplysia endow it with the ability to
      express multiple modes of oscillatory electrical activity, such as beating and
      bursting. Previous modeling studies examined the ways in which membrane
      conductances contribute to the electrical activity of R15 and the ways in which
      extrinsic modulatory inputs alter the membrane conductances by biochemical
      cascades and influence the electrical activity. The goals of the present study
      were to examine the ways in which electrical activity influences the biochemical
      cascades and what dynamical properties emerge from the ongoing interactions
      between electrical activity and these cascades. The model proposed by Butera et
      al. in 1995 was extended to include equations for the binding of Ca(2+) to
      calmodulin (CaM) and the actions of Ca(2+)/CaM on both adenylyl cyclase and
      phosphodiesterase. Simulations indicated that levels of cAMP oscillated during
      bursting and that these oscillations were approximately antiphasic to the
      oscillations of Ca(2+). In the presence of cAMP oscillations, brief perturbations
      could switch the electrical activity between bursting and beating (bistability).
      Compared with a constant-cAMP model, oscillations of cAMP substantially expanded
      the range of bistability. Moreover, the integrated electrical/biochemical model
      simulated some early experimental results such as activity-dependent inactivation
      of the anomalous rectifier. The results of the present study suggest that the
      endogenous activity of R15 depends, in part, on interactions between electrical
      activity and biochemical cascades.

PMID- 14702332
TI  - A model of reverse spike frequency adaptation and repetitive firing of
      subthalamic nucleus neurons.
AB  - Subthalamic nucleus neurons exhibit reverse spike-frequency adaptation. This
      occurs only at firing rates of 20-50 spikes/s and higher. Over this same
      frequency range, there is an increase in the steady-state frequency-intensity (F
      I) curve's slope (the secondary range). Specific blockade of high-voltage
      activated calcium currents reduced the F-I curve slope and reverse adaptation.
      Blockade of calcium-dependent potassium current enhanced secondary range firing.
      A simple model that exhibited these properties used spike-triggered conductances
      similar to those in subthalamic neurons. It showed: 1) Nonaccumulating spike
      afterhyperpolarizations produce positively accelerating F-I curves and spike
      frequency adaptation that is complete after the second spike. 2) Combinations of
      accumulating aftercurrents result in a linear F-I curve, whose slope depends on
      the relative contributions of inward and outward currents. Spike-frequency
      adaptation can be gradual. 3) With both accumulating and nonaccumulating
      aftercurrents, primary and secondary ranges will be present in the F-I curve. The
      slope of the primary range is determined by the nonaccumulating conductance; the
      accumulating conductances govern the secondary range. The transition is
      determined by the relative strengths of accumulating and nonaccumulating
      currents. 4) Spike-threshold accommodation contributes to the secondary range,
      reducing its slope at high firing rates. Threshold accommodation can stabilize
      firing when inward aftercurrents exceed outward ones. 5) Steady-state reverse
      adaptation results when accumulated inward aftercurrents exceed outward ones.
      This requires spike-threshold accommodation. Transient speedup arises when inward
      currents are smaller than outward ones at steady state, but accumulate more
      rapidly. 6) The same mechanisms alter firing in response to irregular patterns of
      synaptic conductances, as cell excitability fluctuates with changes in firing
      rate.

PMID- 14702333
TI  - Forskolin-induced LTP in the CA1 hippocampal region is NMDA receptor dependent.
AB  - Chemically induced long-term potentiation (cLTP) could potentially work by
      directly stimulating the biochemical machinery that underlies synaptic
      plasticity, bypassing the need for synaptic activation. Previous reports
      suggested that agents that raise cAMP concentration might have this capability.
      We examined the cLTP induced in acute slices by application of Sp-cAMPS or a
      combination of the adenylyl cyclase activator, forskolin, and the
      phosphodiesterase inhibitor, rolipram. Under our conditions, cLTP was induced but
      only if inhibition was reduced. We found that this form of cLTP was blocked by a
      N-methyl-d-aspartate receptor (NMDAR) antagonist and required the low-frequency
      test stimulation typically used to monitor the strength of synapses.
      Interestingly, similar LTP could be induced by lowering the Mg(2+) concentration
      of the ACSF during forskolin/rolipram or Sp-cAMPS application or even by just
      lowering Mg(2+) concentration alone. This LTP was also NMDAR dependent and
      required only a few ( approximately 5) low-frequency stimuli for its induction.
      The finding that even low-frequency synaptic stimulation was sufficient for LTP
      induction indicates that a highly sensitized plasticity state was generated. The
      fact that some stimulation was required means that potentiation is probably
      restricted to the stimulated axons, limiting the usefulness of this form of cLTP.
      However, when similar experiments were conducted using slice cultures,
      potentiation occurred without test stimuli, probably because the CA3-CA1
      connections are extensive and because presynaptic spontaneous activity is
      sufficient to fulfill the activity requirement. As in acute slices, the
      potentiation was blocked by an NMDAR antagonist. Our general conclusion is that
      the induction of LTP caused by elevating cAMP requires presynaptic activity and
      NMDA channel opening. The method of inducing cLTP in slice cultures will be
      useful when it is desirable to produce NMDAR-dependent LTP in a large fraction of
      synapses.

PMID- 14702334
TI  - Increased neuronal firing in computer simulations of sodium channel mutations
      that cause generalized epilepsy with febrile seizures plus.
AB  - Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant
      familial syndrome with a complex seizure phenotype. It is caused by mutations in
      one of 3 voltage-gated sodium channel subunit genes (SCN1B, SCN1A, and SCN2A) and
      the GABA(A) receptor gamma2 subunit gene (GBRG2). The biophysical
      characterization of 3 mutations (T875M, W1204R, and R1648H) in SCN1A, the gene
      encoding the CNS voltage-gated sodium channel alpha subunit Na(v)1.1,
      demonstrated a variety of functional effects. The T875M mutation enhanced slow
      inactivation, the W1204R mutation shifted the voltage dependency of activation
      and inactivation in the negative direction, and the R1648H mutation accelerated
      recovery from inactivation. To determine how these changes affect neuronal
      firing, we used the NEURON simulation software to design a computational model
      based on the experimentally determined properties of each GEFS+ mutant sodium
      channel and a delayed rectifier potassium channel. The model predicted that
      W1204R decreased the threshold, T875M increased the threshold, and R1648H did not
      affect the threshold for firing a single action potential. Despite the different
      effects on the threshold for firing a single action potential, all of the
      mutations resulted in an increased propensity to fire repetitive action
      potentials. In addition, each mutation was capable of driving repetitive firing
      in a mixed population of mutant and wild-type channels, consistent with the
      dominant nature of these mutations. These results suggest a common physiological
      mechanism for epileptogenesis resulting from sodium channel mutations that cause
      GEFS+.

PMID- 14702335
TI  - Using auditory and visual stimuli to investigate the behavioral and neuronal
      consequences of reflexive covert orienting.
AB  - Reflexively orienting toward a peripheral cue can influence subsequent responses
      to a target, depending on when and where the cue and target appear relative to
      each other. At short delays between the cue and target [cue-target onset
      asynchrony (CTOA)], subjects are faster to respond when they appear at the same
      location, an effect referred to as reflexive attentional capture. At longer
      CTOAs, subjects are slower to respond when the two appear at the same location,
      an effect referred to as inhibition of return (IOR). Recent evidence suggests
      that these phenomena originate from sensory interactions between the cue- and
      target-related responses. The capture of attention originates from a strong
      target-related response, derived from the overlap of the cue- and target-related
      activities, whereas IOR corresponds to a weaker target-aligned response. If such
      interactions are responsible, then modifying their nature should impact the
      neuronal and behavioral outcome. Monkeys performed a cue-target saccade task
      featuring visual and auditory cues while neural activity was recorded from the
      superior colliculus (SC). Compared with visual stimuli, auditory responses are
      weaker and occur earlier, thereby decreasing the likelihood of interactions
      between these signals. Similar to previous studies, visual stimuli evoked
      reflexive attentional capture at a short CTOA (60 ms) and IOR at longer CTOAs
      (160 and 610 ms) with corresponding changes in the target-aligned activity in the
      SC. Auditory cues used in this study failed to elicit either a behavioral effect
      or modification of SC activity at any CTOA, supporting the hypothesis that
      reflexive orienting is mediated by sensory interactions between the cue and
      target stimuli.

PMID- 14702336
TI  - Spontaneous REM sleep is modulated by the activation of the pedunculopontine
      tegmental GABAB receptors in the freely moving rat.
AB  - Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid
      (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are
      critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and
      its various receptors are normally present in the PPT cholinergic cell
      compartment. The aim of this study was to identify the role of GABA and its
      receptors in the regulation of REM sleep. To achieve this aim, specific receptors
      were activated differentially by local microinjection of selective GABA receptor
      agonists into the PPT while quantifying its effects on REM sleep in freely moving
      chronically instrumented rats (n = 21). The results demonstrated that when GABAB
      receptors were activated by local microinjection of a GABAB receptor selective
      agonist, baclofen, spontaneous REM sleep was suppressed in a dose-dependent
      manner. The optimum dose for REM sleep reduction was 1.5 nmol. In contrast, when
      GABAA and GABAC receptors were activated by microinjecting their receptor
      selective agonists, isoguvacine (ISGV) and cis-4-aminocrotonic acid (CACA),
      respectively, the total percentages of REM sleep did not change compared with the
      control values. In another eight freely moving rats, effects of baclofen
      application was tested on firing rates of REM-on cells (n = 12). Of those 12
      neurons, 11 stopped firing immediately after application of baclofen [latency: 50
      +/- 14 s (SD)] and remained almost silent for 130 +/- 12 min. Findings of the
      present study provide direct evidence that the PPT GABAB receptors and REM-on
      cells are involved in the regulation of REM sleep.

PMID- 14702337
TI  - Frequency-specific effects on cochlear responses during activation of the
      inferior colliculus in the Guinea pig.
AB  - The inferior colliculus (IC) is a major processing center in the ascending
      auditory pathway. The role of the IC in the descending efferent auditory system
      is less clear. Although the IC central nucleus (ICC) is the major relay station
      for the ascending auditory pathways, the IC's cortex receives its main input from
      the neocortex and nonauditory sources. The goal of this study was to determine if
      the IC subdivisions had different functions in the descending efferent auditory
      system. IC subdivisions were identified by their tuning curves evoked by tone
      stimulation, and the effects of localized electrical stimulation on the cochlear
      whole-nerve action potential (CAP). Sharp tuning curves were obtained from ICC in
      contrast to broad tuning curves from the lateral, external cortex. Electrical
      stimulation within the central nucleus had a sharply tuned effect on the CAP. The
      frequency region affected within the cochlea closely matched the best frequency
      of local cells within the central nucleus. The effect of electrical stimulation
      within the lateral, external cortex on the CAP was smaller in comparison to
      central nucleus stimulation. Similar to the broad tuning of cells within the
      lateral cortex, electrical stimulation had a broad frequency effect on CAP
      thresholds.

PMID- 14702338
TI  - Activation of the smooth muscle-specific telokin gene by thyrotroph embryonic
      factor (TEF).
AB  - Transcription of the telokin gene is restricted to smooth muscle cells throughout
      development, making this gene an excellent model for unraveling the mechanisms
      that regulate gene expression in smooth muscle tissues. To identify proteins that
      bind to the telokin promoter, the AT-rich/CArG core of the promoter was used as a
      probe to perform a Southwestern screen of a mouse bladder cDNA library. Four
      clones corresponding to two distinct isoforms of mouse thyrotroph embryonic
      factor (TEFalpha and TEFbeta) were identified from this screen. The two TEF
      isoforms differ from each other at their amino termini and result from
      alternative promoter usage. An RNase protection assay showed that both TEF
      isoforms are expressed at high levels in mouse lung, bladder, kidney, gut, and
      brain. Gel mobility shift assays demonstrated that purified TEF protein can
      specifically bind to an AT-rich region within the core of the telokin promoter.
      Furthermore, when overexpressed in 10T1/2 cells, TEF significantly increased the
      activity of a telokin promoter-reporter gene; this activation was further
      augmented by elevated intracellular calcium levels. In contrast, overexpression
      of TEF had no effect on reporter genes driven by SM22alpha, smooth muscle alpha
      actin, or smooth muscle myosin heavy chain promoters. Consistent with these
      results, overexpression of TEFalpha and TEFbeta in A10 cells, using adenoviral
      vectors, increased expression of endogenous telokin without altering expression
      of myosin light chain 20, SM22alpha, smooth muscle alpha-actin, or calponin.
      These findings suggest that TEF factors contribute to the activation of the
      telokin promoter in smooth muscle cells in a calcium-dependent manner. These data
      also suggest that distinct transcription factors are required to control the
      expression of different smooth muscle genes in a single tissue.

PMID- 14702339
TI  - N-glycosylation is crucial for folding, trafficking, and stability of human
      tripeptidyl-peptidase I.
AB  - Tripeptidyl-peptidase I (TPP I) is a lysosomal serine-carboxyl peptidase that
      sequentially removes tripeptides from polypeptides. Naturally occurring mutations
      in TPP I are associated with the classic late infantile neuronal ceroid
      lipofuscinosis. Human TPP I has five potential N-glycosylation sites at Asn
      residues 210, 222, 286, 313, and 443. To analyze the role of N-glycosylation in
      the function of the enzyme, we obliterated each N- glycosylation consensus
      sequence by substituting Gln for Asn, either individually or in combinations, and
      expressed mutated cDNAs in Chinese hamster ovary and human embryonic kidney 293
      cells. Here, we demonstrate that human TPP I in vivo utilizes all five N
      glycosylation sites. Elimination of one of these sites, at Asn-286, dramatically
      affected the folding of the enzyme. However, in contrast to other misfolded
      proteins that are retained in the endoplasmic reticulum, only a fraction of
      misfolded TPP I mutant expressed in Chinese hamster ovary cells, but not in human
      embryonic kidney 293 cells, was arrested in the ER, whereas its major portion was
      secreted. Secreted proenzyme formed non-native, interchain disulfide bridges and
      displayed only residual TPP I activity upon acidification. A small portion of TPP
      I missing Asn-286-linked glycan reached the lysosome and was processed to an
      active species; however, it showed low thermal and pH stability. N-Glycans at Asn
      210, Asn-222, Asn-313, and Asn-443 contributed slightly to the specific activity
      of the enzyme and its resistance to alkaline pH-induced inactivation.
      Phospholabeling experiments revealed that N-glycans at Asn-210 and Asn-286 of TPP
      I preferentially accept a phosphomannose marker. Thus, a dual role of
      oligosaccharide at Asn-286 in folding and lysosomal targeting could contribute to
      the unusual, but cell type-dependent, fate of misfolded TPP I conformer and
      represent the molecular basis of the disease process in subjects with naturally
      occurring missense mutation at Asn-286.

PMID- 14702340
TI  - Involvement of suppressor for Gal 1 in the ubiquitin/proteasome-mediated
      degradation of estrogen receptors.
AB  - The proteasome-mediated pathway involves the degradation of several nuclear
      receptors. Previously we demonstrated that the interaction between the suppressor
      for Gal 1 (SUG1) and nuclear receptors, the vitamin D receptor, or the pregnane X
      receptor was involved in proteasome-mediated degradation. In our recent
      experiments, we examined the potential role of SUG1 in the proteasome-mediated
      degradation of estrogen receptors (ER)alpha and -beta. Both ERs interacted with
      SUG1 in a ligand-dependent manner. Functionally, the overexpression of SUG1
      inhibited both ERalpha- and ERbeta-mediated transcription in the presence of
      ligands. Transient expression studies demonstrated that the overexpression of
      wild-type SUG1 generated proteolytic fragments of both ERs and that these
      products were blocked by a proteasome inhibitor. The overexpression of SUG1 also
      enhanced the formation of ubiquitinated proteins of both ERs in the presence of
      ligand. On the other hand, bisphenol A (BSA), which activated ER-mediated
      transcription, did not enhance the interaction between ERbeta and SUG1.
      Furthermore, the degradation of ERbeta was much slower in the presence of BSA
      than in the presence of estradiol or phthalate, which is another endocrine
      disrupting chemical. Also, BSA had no effect on the formation of proteolytic
      fragments of ERbeta, and neither did it have any effect on the ubiquitination of
      ERbeta. These findings indicate that the ubiquitin/proteasome-mediated
      degradation of both ER proteins may involve the interaction of SUG1 with both
      ERs. Moreover, BSA strongly blocked the ubiquitination and degradation of ERbeta
      compared with estradiol, suggesting that BSA may affect the ERbeta-mediated
      transcription of target genes by inhibiting ERbeta degradation.

PMID- 14702341
TI  - Vibrio cholerae thiol peroxidase-glutaredoxin fusion is a 2-Cys TSA/AhpC
      subfamily acting as a lipid hydroperoxide reductase.
AB  - Recently, novel hybrid thiol peroxidase (TPx) proteins fused with a glutaredoxin
      (Grx) were found from some pathogenic bacteria, cyanobacteria, and anaerobic
      sulfur-oxidizing phototroph. The phylogenic tree analysis that was constructed
      from the aligned sequences showed two major branches. Haemophilus influenzae
      TPx.Grx was grouped in one branch as a 1-Cys subfamily of the thiol-specific
      antioxident protein/AhpC family. Most TPx.Grx proteins, including Vibrio cholerae
      TPx.Grx, were grouped in the 2-Cys subfamily. To explain the existence of two
      subgroups in novel hybrid TPx proteins, we have compared the kinetics given by V.
      cholerae TPx.Grx, H. influenzae TPx.Grx, their separated TPx domains, and a set
      of mutants devoid of the redox-active cysteines. The kinetic study described here
      demonstrates clearly that V. cholerae TPx.Grx is a 2-Cys TPx subfamily. For the
      first time, we also demonstrate the lipid peroxidase activity of V. cholerae
      TPx.Grx fusion and suggest the in vivo function of 2-Cys TPx.Grx fusion serving
      as a lipid peroxidase.

PMID- 14702342
TI  - Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes.
AB  - Although somatic stem cells have been reported to exist in various adult organs,
      there have been few reports concerning stem cells in the heart. We here
      demonstrate that Sca-1-positive (Sca-1+) cells in adult hearts have some of the
      features of stem cells. Sca-1+ cells were isolated from adult murine hearts by a
      magnetic cell sorting system and cultured on gelatin-coated dishes. A fraction of
      Sca-1+ cells stuck to the culture dish and proliferated slowly. When treated with
      oxytocin, Sca-1+ cells expressed genes of cardiac transcription factors and
      contractile proteins and showed sarcomeric structure and spontaneous beating.
      Isoproterenol treatment increased the beating rate, which was accompanied by the
      intracellular Ca(2+) transients. The cardiac Sca-1+ cells expressed oxytocin
      receptor mRNA, and the expression was up-regulated after oxytocin treatment. Some
      of the Sca-1+ cells expressed alkaline phosphatase after osteogenic induction and
      were stained with Oil-Red O after adipogenic induction. These results suggest
      that Sca-1+ cells in the adult murine heart have potential as stem cells and may
      contribute to the regeneration of injured hearts.

PMID- 14702343
TI  - Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell
      antigen receptor is dependent on phospholipase C-gamma1.
AB  - The small GTPase, Rap1, is a potent activator of leukocyte integrins and enhances
      the adhesive activity of lymphocyte function-associated antigen-1 (LFA-1) when
      stimulated by the T cell receptor (TCR) or chemokines. However, the mechanism by
      which Rap1 is activated remains unclear. Here, we demonstrate that phospholipase
      C (PLC)-gamma1 plays a critical role in the signaling pathway leading to Rap1
      activation triggered by the TCR. In Jurkat T cells, TCR cross-linking triggered
      persistent Rap1 activation, and SDF-1 (CXCL12) activated Rap1 transiently. A
      phospholipase C inhibitor, U73122, abrogated Rap1 activation triggered by both
      the TCR and SDF-1 (CXCL12). PLC-gamma1-deficient Jurkat T cells showed a marked
      reduction of TCR-triggered Rap1 activation and adhesion to intercellular adhesion
      molecule-1 (ICAM-1) mediated by LFA-1. In contrast, SDF-1-triggered Rap1
      activation and adhesion were not affected in these cells. Transfection of these
      cells with an expression plasmid encoding PLC-gamma1 restored Rap1 activation by
      the TCR and the ability to adhere to ICAM-1, accompanied by polarized LFA-1
      surface clustering colocalized with regulator of adhesion and polarization
      enriched in lymphoid tissues (RAPL). Furthermore, when expressed in Jurkat cells,
      CalDAG-GEFI, a calcium and diacylglycerol-responsive Rap1 exchange factor,
      associated with Rap1, and resulted in enhanced Rap1 activation and adhesion
      triggered by the TCR. Our results demonstrate that TCR activation of Rap1 depends
      on PLC-gamma1. This activity is likely to be mediated by CalDAG-GEFI, which is
      required to activate LFA-1.

PMID- 14702344
TI  - Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from
      activated to quiescent hepatic stellate cells.
AB  - Depletion of peroxisome proliferator-activated receptor gamma (PPARgamma)
      accompanies myofibroblastic transdifferentiation of hepatic stellate cells (HSC),
      the primary cellular event underlying liver fibrogenesis. The treatment of
      activated HSC in vitro or in vivo with synthetic PPARgamma ligands suppresses the
      fibrogenic activity of HSC. However, it is uncertain whether PPARgamma is indeed
      a molecular target of this effect, because the ligands are also known to have
      receptor-independent actions. To test this question, the present study examined
      the effects of forced expression of PPARgamma via an adenoviral vector on
      morphologic and biochemical features of culture-activated HSC. The vector
      mediated expression of PPARgamma itself is sufficient to reverse the morphology
      of activated HSC to the quiescent phenotype with retracted cytoplasm, prominent
      dendritic processes, reduced stress fibers, and accumulation of retinyl
      palmitate. These effects are abrogated by concomitant expression of a dominant
      negative mutant of PPARgamma that prevents transactivation of but not binding to
      the PPAR response element. PPARgamma expression also inhibits the activation
      markers such as the expression of alpha-smooth muscle actin, type I collagen, and
      transforming growth factor beta1; DNA synthesis; and JunD binding to the
      activator protein-1 (AP-1) site and AP-1 promoter activity. Inhibited JunD
      activity by PPARgamma is not due to reduced JunD expression or JNK activity or to
      a competition for p300. But it is due to a JunD-PPARgamma interaction as
      demonstrated by co-immunoprecipitation and glutathione S-transferase pull-down
      analysis. Further, the use of deletion constructs reveals that the DNA binding
      region of PPARgamma is the JunD interaction domain. In summary, our results
      demonstrate that the restoration of PPARgamma reverses the activated HSC to the
      quiescent phenotype and suppresses AP-1 activity via a physical interaction
      between PPARgamma and JunD.

PMID- 14702345
TI  - Structure-activity determinants in paneth cell alpha-defensins: loss-of-function
      in mouse cryptdin-4 by charge-reversal at arginine residue positions.
AB  - Paneth cells secrete microbicidal enteric alpha-defensins into the small
      intestinal lumen, and cryptdin-4 (Crp4) is the most bactericidal of the mouse
      alpha-defensin peptides in vitro. Here, site-directed Arg to Asp mutations in
      Crp4 have been shown to attenuate or eliminate microbicidal activity against all
      of the bacterial species tested regardless of the Arg residue position. R31D/R32D
      charge-reversal mutagenesis at the C terminus and mutations at R16D/R18D,
      R16D/R24D, and R18D/R24D in the Crp4 polypeptide chain eliminated in vitro
      bactericidal activity, blocked peptide-membrane interactions, as well as Crp4
      mediated membrane vesicle disruption. Lys for Arg charge-neutral substitutions in
      (R16K/R18K)-Crp4 did not alter the bactericidal activity relative to Crp4,
      showing that bactericidal activity appears not to require the guanidinium side
      chain of Arg at those two positions. Partial restoration of (R31D/R32D)-Crp4
      bactericidal activity occurred when an electropositive Arg for Gly substitution
      was introduced at the peptide N terminus and the (G1R/R31D/R32D)-Crp4 peptide
      exhibited intermediate membrane binding capability. Also, the loss of peptide
      bactericidal activity in (G1D/R31D/R32D)-Crp4 and (R16D/R24D)-Crp4 mutants
      corresponded with diminished phospholipid vesicle disruptive activity.
      Fluorophore leakage from anionic phospholipid vesicles induced by the charge
      reversal variants was negligible relative to Crp4 and lower than that induced by
      pro-Crp4, the inactive Crp4 precursor. Thus, Arg residues function as
      determinants of Crp4 bactericidal activity by facilitating or enabling target
      cell membrane disruption. The role of the Arg residues, however, was surprisingly
      independent of their position in the polypeptide chain.

PMID- 14702346
TI  - Sorting of ligand-activated epidermal growth factor receptor to lysosomes
      requires its actin-binding domain.
AB  - Ligand-induced down-regulation of the epidermal growth factor receptor (EGFR)
      comprises activation of two sequential transport steps. The first involves
      endocytic uptake by clathrin-coated vesicles, the second transfer of endocytosed
      EGFR from endosomes to lysosomes. Here we demonstrate that the second transport
      step requires a domain of the EGFR that encompasses residues 985-996 and was
      previously found to interact with actin. Deletion of domain 989-994 (Delta989-994
      EGFR) did not interfere with EGFR uptake but completely abrogated its
      degradation. In contrast, both uptake and degradation were affected for K721A
      EGFR, a kinase-deficient EGFR mutant. To measure intracellular EGFR sorting, we
      developed a novel cell fractionation assay toward which cells were co-transfected
      for chicken hepatic lectin, a receptor for agialoglycoproteins. These cells were
      incubated with agialofetuin-coupled colloidal gold, which was targeted to
      lysosomes after receptor-mediated endocytosis. Compartments within the lysosomal
      pathway gained buoyant density because of the presence of colloidal gold and
      could be isolated from cell homogenates by ultracentrifugation through a high
      density sucrose cushion. In contrast to endocytosed wild type EGFR, both Delta989
      994 EGFR and K721A EGFR were largely not retrieved in gold-containing endocytic
      compartments. These results are supported with morphological data. We conclude
      that sorting of endocytosed EGFR into the degradation pathway requires both its
      kinase activity and actin-binding domain.

PMID- 14702347
TI  - SREBP-1 dimerization specificity maps to both the helix-loop-helix and leucine
      zipper domains: use of a dominant negative.
AB  - The mammalian SREBP family contains two genes that code for B-HLH-ZIP proteins
      that bind sequence-specific DNA to regulate the expression of genes involved in
      lipid metabolism. We have designed a dominant negative (DN), termed A-SREBP-1,
      that inhibits the DNA binding of either SREBP protein. A-SREBP-1 consists of the
      dimerization domain of B-SREBP-1 and a polyglutamic acid sequence that replaces
      the basic region. A-SREBP-1 heterodimerizes with either B-SREBP-1 or B-SREBP-2,
      and both heterodimers are more stable than B-SREBP-1 bound to DNA. Circular
      dichroism thermal denaturation studies show that the B-SREBP-1.A-SREBP-1
      heterodimer is -9.8 kcal mol(-1) dimer(-1) more stable than the B-SREBP-1
      homodimer. EMSA assays demonstrate that A-SREBP-1 can inhibit the DNA binding of
      either B-SREBP-1 or B-SREBP-2 in an equimolar competition but does not inhibit
      the DNA binding of the three B-HLH-ZIP proteins MAX, USF, or MITF, even at 100
      molar eq. Chimeric proteins containing the HLH domain of SREBP-1 and the leucine
      zipper from either MAX, USF, or MITF indicate that both the HLH and leucine
      zipper regions of SREBP-1 contribute to its dimerization specificity. Transient
      co-transfection studies demonstrate that A-SREBP-1 can inhibit the
      transactivation of SREBP-1 and SREBP-2 but not USF. A-SREBP-1 may be useful in
      metabolic diseases where SREBP family members are overexpressed.

PMID- 14702349
TI  - ZNF143 mediates basal and tissue-specific expression of human transaldolase.
AB  - Transaldolase regulates redox-dependent apoptosis through controlling NADPH and
      ribose 5-phosphate production via the pentose phosphate pathway. The minimal
      promoter sufficient to drive chloramphenicol acetyltransferase reporter gene
      activity was mapped to nucleotides -49 to -1 relative to the transcription start
      site of the human transaldolase gene. DNase I footprinting with nuclear extracts
      of transaldolase-expressing cell lines unveiled protection of nucleotides -29 to 
      16. Electrophoretic mobility shift assays identified a single dominant DNA
      protein complex that was abolished by consensus sequence for transcription factor
      ZNF143/76 or mutation of the ZNF76/143 motif within the transaldolase promoter.
      Mutation of an AP-2alpha recognition sequence, partially overlapping the ZNF143
      motif, increased TAL-H promoter activity in HeLa cells, without significant
      impact on HepG2 cells, which do not express AP-2alpha. Cooperativity of ZNF143
      with AP-2alpha was supported by supershift analysis of HeLa cells where AP-2 may
      act as cell type-specific repressor of TAL promoter activity. However,
      overexpression of full-length ZNF143, ZNF76, or dominant-negative DNA-binding
      domain of ZNF143 enhanced, maintained, or abolished transaldolase promoter
      activity, respectively, in HepG2 and HeLa cells, suggesting that ZNF143 initiates
      transcription from the transaldolase core promoter. ZNF143 overexpression also
      increased transaldolase enzyme activity. ZNF143 and transaldolase expression
      correlated in 21 different human tissues and were coordinately upregulated 14-
      and 34-fold, respectively, in lactating mammary glands compared with nonlactating
      ones. Chromatin immunoprecipitation studies confirm that ZNF143/73 associates
      with the transaldolase promoter in vivo. Thus, ZNF143 plays a key role in basal
      and tissue-specific expression of transaldolase and regulation of the metabolic
      network controlling cell survival and differentiation.

PMID- 14702348
TI  - Clostridium perfringens alpha-toxin activates the sphingomyelin metabolism system
      in sheep erythrocytes.
AB  - Clostridium perfringens alpha-toxin induces hemolysis of rabbit erythrocytes
      through the activation of glycerophospholipid metabolism. Sheep erythrocytes
      contain large amounts of sphingomyelin (SM) but not phosphatidylcholine. We
      investigated the relationship between the toxin-induced hemolysis and SM
      metabolic system in sheep erythrocytes. Alpha-toxin simultaneously induced
      hemolysis and a reduction in the levels of SM and formation of ceramide and
      sphingosine 1-phosphate (S1P). N-Oleoylethanolamine, a ceramidase inhibitor,
      inhibited the toxin-induced hemolysis and caused ceramide to accumulate in the
      toxin-treated cells. Furthermore, dl-threo-dihydrosphingosine and B-5354c,
      isolated from a novel marine bacterium, both sphingosine kinase inhibitors,
      blocked the toxin-induced hemolysis and production of S1P and caused sphingosine
      to accumulate. These observations suggest that the toxin-induced activation of
      the SM metabolic system is closely related to hemolysis. S1P potentiated the
      toxin-induced hemolysis of saponin-permeabilized erythrocytes but had no effect
      on that of intact cells. Preincubation of lysated sheep erythrocytes with
      pertussis toxin blocked the alpha-toxin-induced formation of ceramide from SM. In
      addition, incubation of C. botulinum C3 exoenzyme-treated lysates of sheep
      erythrocytes with alpha-toxin caused an accumulation of sphingosine and
      inhibition of the formation of S1P. These observations suggest that the alpha
      toxin-induced hemolysis of sheep erythrocytes is dependent on the activation of
      the SM metabolic system through GTP-binding proteins, especially the formation of
      S1P.

PMID- 14702350
TI  - SuUR protein binds to the boundary regions separating forum domains in Drosophila
      melanogaster.
AB  - Forum domains are 50-150 kb DNA fragments that are released during spontaneous
      fragmentation of chromosomes. They are separated by islands of putative
      heterochromatin boundary regions. The SuUR protein, which is involved in the
      control of chromosome organization, is localized exclusively in heterochromatin
      and often colocalizes on chromosomes with Polycomb group proteins. To test
      whether the SuUR protein is associated with boundary regions, we used gel
      retardation assays and found that the SuUR protein binds specifically to boundary
      regions and that boundary regions are under-replicated. These results suggest
      that the regular distribution of boundary regions in chromosomes may represent
      the dispersion of sites designed for chromosomal silencing.

PMID- 14702351
TI  - C-terminal and heparin-binding domains of collagenic tail subunit are both
      essential for anchoring acetylcholinesterase at the synapse.
AB  - The collagen-tailed form of acetylcholinesterase (A(12)-AChE) appears to be
      localized at the neuromuscular junction in association with the transmembrane
      dystroglycan complex through binding of its collagenic tail (ColQ) to the
      proteoglycan perlecan. The heparan sulfate binding domains (HSBD) of ColQ are
      thought to be involved in anchoring ColQ to the synaptic basal lamina. The C
      terminal domain (CTD) of ColQ is also likely involved, but there has been no
      direct evidence. Mutations in COLQ cause endplate AChE deficiency in humans. Nine
      previously reported and three novel mutations are in CTD of ColQ, and most CTD
      mutations do not abrogate formation of A(12)-AChE in transfected COS cells.
      Patient endplates, however, are devoid of AChE, suggesting that CTD mutations
      affect anchoring of ColQ to the synaptic basal lamina. Based on our observations
      that purified AChE can be transplanted to the heterologous frog neuromuscular
      junction, we tested insertion competence of nine naturally occurring CTD mutants
      and two artificial HSBD mutants. Wild-type human A(12)-AChE inserted into the
      frog neuromuscular junction, whereas six CTD mutants and two HSBD mutants did
      not. Our studies establish that the CTD mutations indeed compromise anchoring of
      ColQ and that both HSBD and CTD are essential for anchoring ColQ to the synaptic
      basal lamina.

PMID- 14702353
TI  - HIV treatment and eradication in South Africa.

PMID- 14702352
TI  - Hypoxic regulation of angiopoietin-2 expression in endothelial cells.
AB  - Exposure of endothelial cells to hypoxia-induced angiopoietin-2 (Ang2)
      expression. The increase in Ang2 mRNA levels occurred by transcriptional
      regulation and by post-transcriptional increase in mRNA stability. Induction of
      Ang2 mRNA resulted in an increase of intracellular and secreted Ang2 protein
      levels. Since the transcriptional regulation of several genes involved in
      angiogenesis during hypoxia is mediated by hypoxia-inducible factor-1 (HIF-1), it
      was conceivable that Ang2 expression might be regulated by the same oxygen
      dependent mechanism. However, our data showed that pharmacological HIF inducers,
      CoCl(2) and DFO, did not affect Ang2 expression. Moreover, HIF-1-deficient
      hepatoma cell (Hepa1 c4) and its wild-type counterpart (Hepa1 c1c4) up-regulates
      Ang2 during hypoxia. These results indicated that hypoxia-driven Ang2 expression
      may be independent of the HIF pathway. Using neutralizing VEGF antibody or
      pharmacological inhibitors of VEGF receptors, we showed that hypoxia-induced VEGF
      participates but could not account completely for Ang2 expression during hypoxia.
      In addition, hypoxia elicited an increase of cyclooxygenase-2 (COX-2) expression
      and a parallel increase in prostanglandin E(2) (PGE(2)) and prostacyclin (PGI(2))
      production. COX-2 inhibitors decreased the hypoxic induction of Ang2 and the
      hypoxic induction of PGE(2) and PGI(2) in a dose-dependent manner. Similarly, COX
      2 but not COX-1 antisense treatment decreased hypoxic induction of Ang2
      expression, and this effect was reversed by exogenous PGE(2). Finally, exogenous
      PGE(2) and PGI(2) were able to stimulate Ang2 under normoxic conditions. These
      findings suggest that COX-2-dependent prostanoids may play an important role in
      the regulation of hypoxia-induced Ang2 expression.

PMID- 14702354
TI  - Medical schools: are we paying for education or for technical training?

PMID- 14702355
TI  - The deceptive brain.

PMID- 14702356
TI  - The ramifications of HLA-B27.

PMID- 14702357
TI  - When is drug treatment not necessary in epilepsy? Factors that should influence
      the decision to prescribe.

PMID- 14702358
TI  - Smoking rates in the staff of a military field hospital before and after wartime
      deployment.
AB  - In the past, high rates of cigarette smoking have been reported in the British
      Armed Forces. We conducted an anonymous questionnaire survey in the 623 employees
      and attached staff of 34 Field Hospital on their sixth week of deployment to
      Iraq, in the course of Gulf War II. Information was sought on smoking status
      before and during the deployment, and self-declared reasons for smoking. 556
      questionnaires were returned (response rate 89%). The median age of respondents
      was 33.3 SD 7.9 years (range 18-62) and 61% were male. Before deployment the
      number of regular smokers was 160 (29%) but it had now risen by 52 to 212 (38%).
      Of the extra smokers 33 were restarting an old habit but 19 were first-timers.
      Moreover, those who were regular smokers before deployment increased their daily
      consumption from a mean of 15 cigarettes to 21. Smoking rates did not differ
      between clinical and non-clinical staff or between men and women; the rates were
      lower in officers than in non-officers, and in reservists than in regular Army
      personnel. The reasons most commonly cited for starting smoking or increasing
      consumption were boredom, social factors and stress. Few respondents could recall
      having received smoking-related health education during previous service with the
      military. Smoking rates in this medical unit increased substantially during the
      overseas deployment. There were no data on cigarette consumption after return to
      ordinary duties, so we cannot say whether these effects are short-term or long
      term. However, even the pre-existing rate of 42% in regular army personnel is
      high enough to demand urgent action by an employer.

PMID- 14702359
TI  - Recurrent ventricular tachycardia of non-ischaemic origin.

PMID- 14702360
TI  - A rapidly increasing pleural effusion.

PMID- 14702361
TI  - Wandering hemiparesis.

PMID- 14702362
TI  - Pulmonary embolism--or vasculitis?

PMID- 14702363
TI  - Pneumoperitoneum in CAPD peritonitis.

PMID- 14702364
TI  - Enteritis cystica profunda.

PMID- 14702365
TI  - Painful lesions at the fingertips.

PMID- 14702366
TI  - Nerve gas antidotes.

PMID- 14702367
TI  - Art and medicine 1: Health hazards by Dr Jane Jackson.

PMID- 14702368
TI  - Charles Scott Sherrington's Integrative action: a centenary notice.

PMID- 14702369
TI  - Child adoption in the seventeenth century: vignettes from Defoe and Pepys.

PMID- 14702370
TI  - CAM and EBM: arguments for convergence.

PMID- 14702371
TI  - Patient choice and complementary medicine.

PMID- 14702372
TI  - Hardship and empathy.

PMID- 14702373
TI  - The toll of road traffic accidents.

PMID- 14702374
TI  - Biochemical investigations in geophagia.

PMID- 14702375
TI  - Gastro-oesophageal reflux.

PMID- 14702376
TI  - Gastro-oesophageal reflux.

PMID- 14702377
TI  - Guestimates.

PMID- 14702378
TI  - Haemopneumothorax after fine needle aspiration of the breast.

PMID- 14702379
TI  - What should the citizen know about science?

PMID- 14702380
TI  - The first laparoscopic surgeons.

PMID- 14702382
TI  - Joyce Taylor-Papadimitriou. Interview by Fiona Watt.

PMID- 14702383
TI  - The role of the CD44 transmembrane and cytoplasmic domains in co-ordinating
      adhesive and signalling events.
AB  - CD44 is a widely distributed type I transmembrane glycoprotein and functions as
      the major hyaluronan receptor on most cell types. Although alternative splicing
      can produce a large number of different isoforms, they all retain the hyaluronan
      binding Link-homology region and a common transmembrane and cytoplasmic domain,
      which are highly conserved between species. The past decade has seen an extensive
      investigation of this receptor owing to its importance in mediating cell-cell and
      cell-matrix interactions in both normal and disease states. Although roles for
      alternative splicing and variable glycosylation in determining ligand-binding
      interactions are now well established, the mechanisms by which CD44 integrates
      structural and signalling events to elicit cellular responses have been less well
      understood. However, there is now increasing evidence that CD44 is assembled in a
      regulated manner into membrane-cytoskeletal junctional complexes and, through
      both direct and indirect interactions, serves to focus downstream signal
      transduction events.

PMID- 14702384
TI  - Trans-Golgi network delivery of synaptic proteins in synaptogenesis.
AB  - Synapse formation, stabilization and maintenance comprise several remarkably
      precise and rapid stages. The initial steps involve delivery to the site of
      initial contact between axon and dendrite of transport carriers containing
      several sets of synaptic proteins necessary for proper synaptic function. This
      occurs both pre- and postsynaptically and is mediated by apparently distinct
      vesicular carriers that fuse with the synaptic plasma membrane to deliver
      receptors for neurotransmitters, ion channels, transporters and pumps. The
      presynaptic carriers in the developing axon give rise to synaptic vesicles. On
      the postsynaptic side, the so-called spine apparatus may represent a tubular
      reservoir that gives rise to the postsynaptic players in synaptic function.
      Recent evidence indicates that recognition molecules, particularly neural cell
      adhesion molecule (NCAM), are associated with trans-Golgi-network-derived
      structures and thus can provide a signal for accumulation of these transport
      carriers at nascent synapses.

PMID- 14702385
TI  - Forespore membrane assembly in yeast: coordinating SPBs and membrane trafficking.
AB  - In the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae, sporulation
      involves de novo synthesis of forespore membrane (FSM) within the cytoplasm of
      mother cells. The FSM ultimately becomes the plasma membrane of the developing
      ascospores. Several protein components of the FSM have been identified.
      Visualization of these proteins has demonstrated the dynamic nature of the
      genesis and development of the FSM. It begins to develop at the differentiated
      outer plaque of the spindle pole bodies (SPBs) and extends outwards,
      encapsulating each of the haploid nuclei produced by meiosis. Several coiled-coil
      proteins are specifically recruited to the SPBs and play indispensable roles in
      FSM assembly. Temporal and spatial coordination of meiotic nuclear divisions and
      membrane assembly is of special importance. Comparison of the processes of FSM
      assembly in these yeasts shows that the basic mechanism has been conserved, even
      though the individual proteins involved are often different. Understanding these
      dynamic aspects of yeast sporulation will help to elucidate a general mechanism
      for the cellularization of cytoplasm containing multiple nuclei.

PMID- 14702386
TI  - Runx2 deficiency in chondrocytes causes adipogenic changes in vitro.
AB  - Runx2 (runt-related transcription factor 2) is an important transcription factor
      for chondrocyte differentiation as well as for osteoblast differentiation. To
      investigate the function of Runx2 in chondrocytes, we isolated chondrocytes from
      the rib cartilage of Runx2-deficient (Runx2-/-) mice and examined the effect of
      Runx2 deficiency on chondrocyte function and behavior in culture for up to 12
      days. At the beginning of the culture, Runx2-/- chondrocytes actively
      proliferated, had a polygonal shape and expressed type II collagen; these are all
      characteristics of chondrocytes. However, they gradually accumulated lipid
      droplets that stained with oil red O and resembled adipocytes. Northern blot
      analysis revealed that the expression of adipocyte-related differentiation marker
      genes including PPAR gamma (peroxisome proliferator-activated receptor gamma),
      aP2 and Glut4 increased over time in culture, whereas expression of type II
      collagen decreased. Furthermore, the expression of Pref-1, an important
      inhibitory gene of adipogenesis, was remarkably decreased. Adenoviral
      introduction of Runx2 or treatment with transforming growth factor-beta, retinoic
      acid, interleukin-1 beta, basic fibroblast growth factor, platelet-derived growth
      factor or parathyroid hormone inhibited the adipogenic changes in Runx2-/-
      chondrocytes. Runx2 and transforming growth factor-beta synergistically
      upregulated interleukin-11 expression, and the addition of interleukin-11 to the
      culture medium reduced adipogenesis in Runx2-/- chondrocytes. These findings
      indicate that depletion of Runx2 resulted in the loss of the differentiated
      phenotype in chondrocytes and induced adipogenic differentiation in vitro, and
      show that Runx2 plays important roles in maintaining the chondrocyte phenotype
      and in inhibiting adipogenesis. Our findings suggest that these Runx2-dependent
      functions are mediated, at least in part, by interleukin-11.

PMID- 14702387
TI  - Maternally expressed and partially redundant beta-tubulins in Caenorhabditis
      elegans are autoregulated.
AB  - The mitotic spindle, which partitions replicated chromosomes to daughter cells
      during cell division, is composed of microtubule assemblies of alpha/beta-tubulin
      heterodimers. Positioning of the mitotic spindle influences the size and location
      of daughter cells, and can be important for the proper partitioning of
      developmental determinants. We describe two semi-dominant mis-sense mutations in
      tbb-2, one of two C. elegans beta-tubulin genes that are maternally expressed and
      together are required for microtubule-dependent processes in the early embryo.
      These mutations result in a posteriorly displaced and misoriented mitotic spindle
      during the first cell division. In contrast, a probable tbb-2 null allele is
      recessive, and when homozygous results in less severe spindle positioning defects
      and only partially penetrant embryonic lethality. Two of the tbb-2 mutations
      result in reduced levels of TBB-2 protein, and increased levels of a second
      maternally expressed beta-tubulin, TBB-1. However, levels of TBB-1 are not
      increased in a tbb-2 mutant with an allele that does not result in reduced levels
      of TBB-2 protein. We conclude that feedback regulation influences maternal beta
      tubulin expression in C. elegans, but cannot fully restore normal microtubule
      function in the absence of one beta-tubulin isoform.

PMID- 14702389
TI  - Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates
      DNA synthesis in cell-cell contact forming cardiomyocytes.
AB  - Mitogenic stimulation of cardiomyocytes is associated with decreased gap junction
      coupling and protein kinase C (PKC)-mediated phosphorylation of the gap junction
      protein connexin43 (Cx43). Identification of and interference with the amino
      acid(s) that becomes phosphorylated in response to stimulation are important
      steps towards defining the relationship between Cx43 phosphorylation and cell
      cycle. Using immunoblotting and phosphospecific antibodies we were able to show
      that serine-262 (S262) on Cx43 becomes phosphorylated in response to growth
      factor or PKC stimulation of cardiomyocytes. To examine the effect of Cx43, S262
      phosphorylation and cell-cell contact (and/or coupling) on DNA synthesis, we
      overexpressed wild-type (wt) or mutant Cx43, carrying a S262-to-alanine (S262A,
      simulating the unphosphorylated state) or a S262-to-aspartate (S262D, simulating
      constitutive phosphorylation) substitutions in cultures of cell-cell contact
      forming or isolated cardiomyocytes. Overexpression of wt-Cx43 caused a
      significant decrease in DNA synthesis irrespective of the presence of cell-cell
      contact. In cell-cell contact forming cultures, the S262D mutation reversed while
      the S262A mutation increased the inhibitory effect of Cx43. In the absence of
      cell-cell contact, the S262-Cx43 mutations had no significant effect on Cx43
      inhibition of DNA synthesis. Dye-coupling, evaluated by scrape-loading, indicated
      increased gap junction permeability in S262A (compared to wt or S262D)
      overexpressing myocytes. We conclude that Cx43 inhibits cardiomyocyte DNA
      synthesis irrespectively of cell-cell contact or coupling. Cell-cell contact, and
      possibly gap junction-mediated communication is required, however, in order to
      reverse Cx43 inhibition of DNA synthesis by S262 phosphorylation.

PMID- 14702388
TI  - The Yin Yang-1 (YY1) protein undergoes a DNA-replication-associated switch in
      localization from the cytoplasm to the nucleus at the onset of S phase.
AB  - The essential Yin Yang-1 gene (YY1) encodes a ubiquitous, conserved,
      multifunctional zinc-finger transcription factor in animals. The YY1 protein
      regulates initiation, activation, or repression of transcription from a variety
      of genes required for cell growth, development, differentiation, or tumor
      suppression, as well as from genes in some retroviruses and DNA viruses. Among
      the specific functions attributed to YY1 is a role in cell-cycle-specific
      upregulation of the replication-dependent histone genes. The YY1 protein binds to
      the histone alpha element, a regulatory sequence found in all replication
      dependent histone genes. We therefore examined the abundance, DNA-binding
      activity and localization of the YY1 protein throughout the cell cycle in
      unperturbed, shake-off-synchronized Chinese hamster ovary and HeLa cells. We
      found that, whereas the DNA-binding activity of YY1 increased dramatically early
      in S phase, the YY1 mRNA and protein levels did not. YY1 changed subcellular
      distribution patterns during the cell cycle, from mainly cytoplasmic at G1 to
      mainly nuclear at early and middle S phase, then back to primarily cytoplasmic
      later in S phase. Nuclear accumulation of YY1 near the G1/S boundary coincided
      with both an increase in YY1 DNA-binding activity and the coordinate up
      regulation of the replication-dependent histone genes. The DNA synthesis
      inhibitor aphidicolin caused a nearly complete loss of nuclear YY1, whereas
      addition of caffeine or 2-aminopurine to aphidicolin-treated cells restored both
      DNA synthesis and YY1 localization in the nucleus. These findings reveal a
      mechanism by which YY1 localization is coupled to DNA synthesis and responsive to
      cell-cycle signaling pathways. Taken together, our results provide insight into
      how YY1 might participate in the cell-cycle control over a variety of nuclear
      events required for cell division and proliferation.

PMID- 14702390
TI  - The principal chloroquine resistance protein of Plasmodium falciparum is a member
      of the drug/metabolite transporter superfamily.

PMID- 14702391
TI  - Integrons or super integrons?

PMID- 14702392
TI  - Did the loss of two-component systems initiate pseudogene accumulation in
      Mycobacterium leprae?

PMID- 14702393
TI  - Development of an insertional expression vector system for Methylobacterium
      extorquens AM1 and generation of null mutants lacking mtdA and/or fch.
AB  - Over the past few years, the genetic 'toolkit' available for use with
      Methylobacterium extorquens AM1 has expanded significantly. Here a further
      advance is presented and demonstrated, an insertional expression system that
      allows expression of genes from a stable, unmarked chromosomal locus. This system
      has been used to better understand the role of the tetrahydrofolate (H4F) pathway
      in methylotrophy. Previously, it has not been possible to generate null mutants
      lacking either mtdA (encoding an NADP-dependent methylene-H4F/methylene
      tetrahydromethanopterin dehydrogenase) or fch (encoding methenyl-H4F
      cyclohydrolase). An unmarked strain was generated that expressed the analogous
      folD gene (encoding a bifunctional NADP-dependent methylene-H4F
      dehydrogenase/methenyl-H4F cyclohydrolase) from Methylobacterium chloromethanicum
      CM4T. In this strain, null mutants could be obtained that grew normally on
      multicarbon substrates but were defective for growth on C1 substrates.
      Additionally, null mutants of mtdA and/or fch could also be generated in the wild
      type by supplementing the succinate medium with formate. These strains were
      unable to grow on C1 compounds but were not methanol-sensitive. These approaches
      have demonstrated that the apparent essentiality of mtdA and fch is due to the
      need for formyl-H4F for biosynthesis of purines and other compounds, and have
      provided clear genetic evidence that the H4F pathway is required for
      methylotrophy.

PMID- 14702394
TI  - The importance of the Tat-dependent protein secretion pathway in Streptomyces as
      revealed by phenotypic changes in tat deletion mutants and genome analysis.
AB  - Streptomyces are Gram-positive soil bacteria that are used industrially, not only
      as a source of medically important natural compounds, but also as a host for the
      secretory production of a number of heterologous proteins. A good understanding
      of the different secretion processes in this organism is therefore of major
      importance. The functionality of the recently discovered bacterial twin-arginine
      translocation (Tat) pathway has already been shown in Streptomyces lividans.
      Here, the aberrant phenotype of S. lividans DeltatatB and DeltatatC single
      mutants is described. Both mutants are characterized by a dispersed growth in
      liquid medium, an impaired morphological differentiation on solid medium and
      growth retardation. To reveal the extent to which the Tat pathway is used in
      Streptomyces, putative Tat-dependent precursor proteins of Streptomyces
      coelicolor, a very close relative of S. lividans, and of Streptomyces
      avermitilis, of which the genomes have been completely sequenced, were identified
      by a modified version of the TATFIND computer program designed by Rose and
      colleagues [Rose, R. W., Bruser, T., Kissinger, J. C. & Pohlschroder, M. (2002).
      Mol Microbiol 45, 943-950]. A list of 230 precursor proteins was obtained; this
      is the highest number of putative Tat substrates found in any genome so far. In
      addition to the Streptomyces antibioticus tyrosinase, it was also demonstrated
      that the secretion of the S. lividans xylanase C is Tat-dependent. The predicted
      Tat substrates belong to a variety of protein classes, with a high number of
      proteins functioning in degradation of macromolecules, in binding and transport,
      and in secondary metabolism. Only a minor fraction of the proteins seem to bind a
      cofactor. The aberrant phenotype of the DeltatatB and DeltatatC mutants together
      with the high number of putative Tat-dependent substrates suggests that the
      Streptomyces Tat pathway has a distinct and more important role in protein
      secretion than in most other bacteria.

PMID- 14702395
TI  - Metronidazole induces programmed cell death in the protozoan parasite
      Blastocystis hominis.
AB  - Previous studies by the authors have shown that the protozoan parasite
      Blastocystis hominis succumbed to a cytotoxic monoclonal antibody with a number
      of cellular and biochemical features characteristic of apoptosis in higher
      eukaryotes. The present study reports that apoptosis-like features are also
      observed in growing cultures of axenic B. hominis upon exposure to metronidazole,
      a drug commonly used for the treatment of blastocystosis. Upon treatment with the
      drug, B. hominis cells displayed key morphological and biochemical features of
      programmed cell death (PCD), viz. nuclear condensation and nicked DNA in nucleus,
      reduced cytoplasmic volume, externalization of phosphatidylserine and maintenance
      of plasma membrane integrity with increasing permeability. This present study
      also supports the authors' previously postulated novel function for the B.
      hominis central vacuole in PCD; it acts as a repository where apoptotic bodies
      are stored before being released into the extracellular space. The implications
      and possible roles of PCD in B. hominis are discussed.

PMID- 14702396
TI  - Characterization of the Staphylococcus aureus mprF gene, involved in lysinylation
      of phosphatidylglycerol.
AB  - Lysylphosphatidylglycerol (LPG) is a basic phospholipid in which L-lysine from
      lysyl-tRNA is transferred to phosphatidylglycerol (PG). This study examined
      whether the Staphylococcus aureus mprF gene encodes LPG synthetase. A crude
      membrane fraction prepared from wild-type S. aureus cells had LPG synthetase
      activity that depended on PG and lysyl-tRNA, whereas the membrane fraction from
      an mprF deletion mutant did not. When S. aureus MprF protein was trans-expressed
      in wild-type Escherichia coli cells, LPG synthesis was induced, whereas it was
      not observed in E. coli pgsA3 mutant cells in which the amount of PG is
      significantly reduced. In addition, LPG synthetase activity and a 93 kDa protein
      whose molecular size corresponded to that of MprF protein were co-induced in the
      crude membrane fraction prepared from E. coli cells expressing MprF protein. The
      Km values of the LPG synthetase activity for PG and for lysyl-tRNA were 56 microM
      and 6.9 microM, respectively, consistent with those of S. aureus membranes. These
      results suggest that the MprF protein is LPG synthetase.

PMID- 14702397
TI  - Characterization of a glycosylphosphatidylinositol-bound cell-wall protein (GPI
      CWP) in Yarrowia lipolytica.
AB  - The structure and composition of the cell wall of yeast has so far been studied
      mainly in Saccharomyces cerevisiae. It is basically made up of three components:
      beta-glucans, chitin and mannose-containing glycoproteins, also called
      mannoproteins. Most covalently bound cell-wall mannoproteins belong to the so
      called glycosylphosphatidylinositol cell-wall protein (GPI-CWP) family, cell-wall
      proteins that are bound through the remnant of a GPI residue to 1,6-beta-glucan.
      The non-conventional yeast Yarrowia lipolytica shares Generally Regarded As Safe
      (GRAS) status with S. cerevisiae, has some industrial applications and is
      increasingly being proposed as a host for the production of recombinant proteins
      and as a model in the study of dimorphism. However, very little information on
      cell-wall structure and composition is available for this organism. Here is
      described the isolation and characterization of YlCWP1, a homologue of the CWP1
      gene from S. cerevisiae, which encodes a GPI-CWP, and the identification of its
      gene product. YlCWP1 encodes a 221 aa protein that contains a putative signal
      peptide and a putative GPI-attachment site. It shows 28.5 % overall identity with
      Cwp1 of S. cerevisiae and a hydropathy profile characteristic of GPI-CWPs.
      Disruption of YlCWP1, both in the wild-type and in an mnn9 glycosylation
      deficient background, led to the identification of Ylcwp1 as a 60 kDa polypeptide
      present in cell-wall extracts. To the authors' knowledge, this is the first
      report of a GPI-CWP in Y. lipolytica, and it suggests that the cell-wall
      organization of Y. lipolytica is similar to that of S. cerevisiae.

PMID- 14702398
TI  - GadE (YhiE): a novel activator involved in the response to acid environment in
      Escherichia coli.
AB  - In several Gram-positive and Gram-negative bacteria glutamate decarboxylases play
      an important role in the maintenance of cellular homeostasis in acid
      environments. Here, new insight is brought to the regulation of the acid response
      in Escherichia coli. Overexpression of yhiE, similarly to overexpression of gadX,
      a known regulator of glutamate decarboxylase expression, leads to increased
      resistance of E. coli strains under high acid conditions, suggesting that YhiE is
      a regulator of gene expression in the acid response. Target genes of both YhiE
      (renamed GadE) and GadX were identified by a transcriptomic approach. In vitro
      experiments with GadE purified protein provided evidence that this regulator
      binds to the promoter region of these target genes. Several of them are clustered
      together on the chromosome and this chromosomal organization is conserved in many
      E. coli strains. Detailed structural (in silico) analysis of this chromosomal
      region suggests that the promoters of the corresponding genes are preferentially
      denatured. These results, along with the G+C signature of the chromosomal region,
      support the existence of a fitness island for acid adaptation on the E. coli
      chromosome.

PMID- 14702399
TI  - Importance of mycoloyltransferases on the physiology of Corynebacterium
      glutamicum.
AB  - Mycoloyltransferases (Myts) play an essential role in the biogenesis of the cell
      envelope of members of the Corynebacterineae, a group of bacteria that includes
      the mycobacteria and corynebacteria. While the existence of several functional
      myt genes has been demonstrated in both mycobacteria and corynebacteria (cmyt),
      the disruption of any of these genes has at best generated cell-wall-defective
      but always viable strains. To investigate the importance of Myts on the
      physiology of members of the Corynebacterineae, a double mutant of
      Corynebacterium glutamicum was constructed by deleting cmytA and cmytB, and the
      consequences of the deletion on the viability of the mutant, the transfer of
      corynomycoloyl residues onto its cell-wall arabinogalactan and trehalose
      derivatives, and on its cell envelope ultrastructure were determined. The double
      mutant strain failed to grow at 34 degrees C and exhibited a growth defect and
      formed segmentation-defective cells at 30 degrees C. Biochemical analyses showed
      that the double mutant elaborated 60 % less cell-wall-bound corynomycolates and
      produced less crystalline surface layer proteins associated with the cell surface
      than the parent and cmytA-inactivated mutant strains. Freeze-fracture electron
      microscopy showed that the DeltacmytA DeltacmytB double mutant, unlike the wild
      type and cmytA-inactivated single mutant strains, frequently exhibited an
      additional fracture plane that propagated within the plasma membrane and rarely
      exposed the S-layer protein. Ultra-thin sectioning of the double mutant cells
      showed that they were totally devoid of the outermost layer. Complementation of
      the double mutant with the wild-type cmytA or cmytB gene restored completely or
      partially this phenotype. The data indicate that Myts are important for the
      physiology of C. glutamicum and reinforce the concept that these enzymes would
      represent good targets for the discovery of new drugs against the pathogenic
      members of the Corynebacterineae.

PMID- 14702400
TI  - Biosynthesis of the dichloroacetyl component of chloramphenicol in Streptomyces
      venezuelae ISP5230: genes required for halogenation.
AB  - Five ORFs were detected in a fragment from the Streptomyces venezuelae ISP5230
      genomic DNA library by hybridization with a PCR product amplified from primers
      representing a consensus of known halogenase sequences. Sequencing and functional
      analyses demonstrated that ORFs 11 and 12 (but not ORFs 13-15) extended the
      partially characterized gene cluster for chloramphenicol (Cm) biosynthesis in the
      chromosome. Disruption of ORF11 (cmlK) or ORF12 (cmlS) and conjugal transfer of
      the insertionally inactivated genes to S. venezuelae gave mutant strains VS1111
      and VS1112, each producing a similar series of Cm analogues in which
      unhalogenated acyl groups replaced the dichloroacetyl substituent of Cm. 1H-NMR
      established that the principal metabolite in the disrupted strains was the alpha
      N-propionyl analogue. The sequence of CmlK implicated the protein in adenylation,
      and involvement in halogenation was inferred from biosynthesis of analogues by
      the cmlK-disrupted mutant. A role in generating the dichloroacetyl substituent
      was supported by partial restoration of Cm biosynthesis when a cloned copy of
      cmlK was introduced in trans into VS1111. Complementation of the mutant also
      indicated that inactivation of cmlK rather than a polar effect of the disruption
      on cmlS expression had interfered with dichloroacetyl biosynthesis. The deduced
      CmlS sequence resembled sequences of FADH2-dependent halogenases. Conjugal
      transfer of cmlK or cmlS into S. venezuelae cml-2, a chlorination-deficient
      strain with a mutation mapped genetically to the Cm biosynthesis gene cluster,
      did not complement the cml-2 lesion, suggesting that one or more genes in
      addition to cmlK and cmlS is needed to assemble the dichloroacetyl substituent.
      Insertional inactivation of ORF13 did not affect Cm production, and the products
      of ORF14 and ORF15 matched Streptomyces coelicolor A3(2) proteins lacking
      plausible functions in Cm biosynthesis. Thus cmlS appears to mark the downstream
      end of the gene cluster.

PMID- 14702401
TI  - Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus.
AB  - The glycopeptide teicoplanin is used for the treatment of serious infections
      caused by Gram-positive pathogens. The tcp gene cluster, devoted to teicoplanin
      biosynthesis in the actinomycete Actinoplanes teichomyceticus, was isolated and
      characterized. From sequence analysis, the tcp cluster spans approximately 73 kb
      and includes 39 ORFs participating in teicoplanin biosynthesis, regulation,
      resistance and export. Of these, 34 ORFs find a match in at least one of the five
      glycopeptide gene clusters previously characterized. Putative roles could be
      assigned for most of the tcp genes. The two glycosyltransferases responsible for
      attaching amino sugars to amino acids 4 and 6 of the teicoplanin aglycon were
      overexpressed in Escherichia coli and characterized. They both recognize N
      acetylglucosamine as the substrate. tGtfA can add a sugar residue in the presence
      or absence of N-acetylglucosamine at amino acid 4, while tGtfB can only
      glycosylate the teicoplanin aglycon.

PMID- 14702402
TI  - Bovicin HJ50, a novel lantibiotic produced by Streptococcus bovis HJ50.
AB  - A bacteriocin-producing strain was isolated from raw milk and named Streptococcus
      bovis HJ50. Like most bacteriocins produced by lactic acid bacteria, bovicin HJ50
      showed a narrow range of inhibiting activity. It was sensitive to trypsin,
      subtilisin and proteinase K. Bovicin HJ50 was extracted by n-propanol and
      purified by SP Sepharose Fast Flow, followed by Phenyl Superose and Sephadex G
      50. Treatment of Micrococcus flavus NCIB8166 with bovicin HJ50 revealed potassium
      efflux from inside the cell in a concentration-dependent manner. The molecular
      mass of bovicin HJ50 was determined to be 3428.3 Da. MS analysis of DTT-treated
      bovicin HJ50 suggested that bovicin HJ50 contains a disulfide bridge. The
      structural gene of bovicin HJ50 was cloned by nested PCR based on its N-terminal
      amino acid sequence. Sequence analysis showed that it encodes a 58 aa prepeptide
      consisting of an N-terminal leader sequence of 25 aa and a C-terminal propeptide
      domain of 33 aa. Bovicin HJ50 shows similarity to type AII lantibiotics. Chemical
      modification using an ethanethiol-containing reaction mixture showed that two Thr
      residues are modified.

PMID- 14702403
TI  - Aspirin commits yeast cells to apoptosis depending on carbon source.
AB  - The effect of aspirin on the growth of a wild-type Saccharomyces cerevisiae
      strain (EG103), containing both copper,zinc superoxide dismutase (CuZnSOD) and
      manganese superoxide dismutase (MnSOD), a strain deficient in MnSOD (EG110) and a
      strain deficient in CuZnSOD (EG118) was measured in media containing different
      carbon sources. Aspirin inhibited the fermentative growth of all three strains in
      glucose medium. It inhibited the non-fermentative growth of the MnSOD-deficient
      strain very drastically in ethanol medium and had no effect on this strain in
      glycerol or acetate medium. The non-fermentative growth of the other two strains
      was not affected by aspirin. The growth inhibition of strain EG110 was associated
      with early necrosis in glucose medium and late apoptosis in ethanol medium. The
      apoptosis was preceded by a pronounced loss of cell viability. The growth
      inhibitory effect of aspirin was not reversed by the antioxidants N
      acetylcysteine and vitamin E. Furthermore, aspirin itself appeared to act as an
      antioxidant until the onset of overt apoptosis, when a moderate increase in the
      intracellular oxidation level occurred. This suggested that reactive oxygen
      species probably do not play a primary role in the apoptosis of cells exposed to
      aspirin.

PMID- 14702404
TI  - Azorhizobium caulinodans electron-transferring flavoprotein N electrochemically
      couples pyruvate dehydrogenase complex activity to N2 fixation.
AB  - Azorhizobium caulinodans thermolabile point mutants unable to fix N2 at 42
      degrees C were isolated and mapped to three, unlinked loci; from complementation
      tests, several mutants were assigned to the fixABCX locus. Of these, two
      independent fixB mutants carried missense substitutions in the product electron
      transferring flavoprotein N (ETFN) alpha-subunit. Both thermolabile missense
      variants Y238H and D229G mapped to the ETFNalpha interdomain linker. Unlinked
      thermostable suppressors of these two fixB missense mutants were identified and
      mapped to the lpdA gene, encoding dihydrolipoamide dehydrogenase (LpDH),
      immediately distal to the pdhABC genes, which collectively encode the pyruvate
      dehydrogenase (PDH) complex. These two suppressor alleles encoded LpDH NAD
      binding domain missense mutants G187S and E210G. Crude cell extracts of these
      fixB lpdA double mutants showed 60-70% of the wild-type PDH activity; neither
      fixB lpdA double mutant strain exhibited any growth phenotype at the restrictive
      or the permissive temperature. The genetic interaction between two combinations
      of lpdA and fixB missense alleles implies a physical interaction of their
      respective products, LpDH and ETFN. Presumably, this interaction
      electrochemically couples LpDH as the electron donor to ETFN as the electron
      acceptor, allowing PDH complex activity (pyruvate oxidation) to drive soluble
      electron transport via ETFN to N2, which acts as the terminal electron acceptor.
      If so, then, the A. caulinodans PDH complex activity sustains N2 fixation both as
      the driving force for oxidative phosphorylation and as the metabolic electron
      donor.

PMID- 14702405
TI  - The Clostridium perfringens TetA(P) efflux protein contains a functional variant
      of the Motif A region found in major facilitator superfamily transport proteins.
AB  - The Clostridium perfringens tetracycline resistance protein, TetA(P), is an inner
      membrane protein that mediates the active efflux of tetracycline from the
      bacterial cell. This protein comprises 420 aa and is predicted to have 12
      transmembrane domains (TMDs). Comparison of the TetA(P) amino acid sequence to
      that of several members of the major facilitator superfamily (MFS) identified a
      variant copy of the conserved Motif A. This region consists of the sequence
      E59xPxxxxxDxxxRK72 and is located within the putative loop joining TMDs 2 and 3
      in the predicted structural model of the TetA(P) protein. To study the functional
      importance of the conserved residues, site-directed mutagenesis was used to
      construct 17 point mutations that were then analysed for their effect on
      tetracycline resistance and their ability to produce an immunoreactive TetA(P)
      protein. Changes to the conserved Phe-58 residue were tolerated, whereas three
      independent substitutions of Pro-61 abolished tetracycline resistance.
      Examination of the basic residues showed that Arg-71 is required for function,
      whereas tetracycline resistance was retained when Lys-72 was substituted with
      arginine. These results confirm that the region encoding this motif is important
      for tetracycline resistance and represents a distant version of the Motif A
      region found in other efflux proteins and members of the MFS family. In addition,
      it was shown that Glu-117 of the TetA(P) protein, which is predicted to be
      located in TMD4, is important for resistance although a derivative with an
      aspartate residue at this position is also functional.

PMID- 14702407
TI  - Protein kinase A is involved in the control of morphology and branching during
      aerobic growth of Mucor circinelloides.
AB  - The cAMP signal transduction pathway controls many processes in fungi. The Mucor
      circinelloides pkaR and pkaC genes, encoding the regulatory (PKAR) and catalytic
      (PKAC) subunit of the cAMP-dependent protein kinase A (PKA), have been cloned
      recently. Expression analysis during the dimorphic shift and colony morphology
      suggested a role for PKAR in the control of morphology and branching. Here strain
      KFA121, which overexpresses the M. circinelloides pkaR gene, was used to quantify
      growth and branching under different aerobic growth conditions in a flow-through
      cell by computerized image analysis. An inverse relationship between the pkaR
      expression level in KFA121 and the hyphal growth unit length was observed in
      KFA121, suggesting a central role for PKAR in branching. A biochemical analysis
      of PKAR using antibodies and enzyme assay demonstrated that the level of PKAR is
      higher in KFA121 under inducing conditions, i.e. in the presence of high glucose,
      than in the vector control strain KFA89. Measurement of cAMP binding demonstrated
      a significant increase (two- to threefold) in PKAR level for KFA121 at the time
      of germ-tube emission in medium containing 10 g glucose l(-1). The level of PKA
      activity was determined using kemptide in the same crude cell extracts used to
      determine cAMP binding. Strain KFA121 showed a twofold increase in PKA activity.
      An excess of free PKAR subunit over PKA holoenzyme was determined using sucrose
      gradient centrifugation of extracts from KFA89 and KFA121. The data indicate that
      cAMP-dependent PKA in M. circinelloides might be down-regulated during hyphal
      tube emergence and that an increase in PKAR levels results in increased
      branching.

PMID- 14702406
TI  - Secretion of immunodominant membrane protein from onion yellows phytoplasma
      through the Sec protein-translocation system in Escherichia coli.
AB  - A gene that encodes a putative SecE protein, which is a component of the Sec
      protein-translocation system, was cloned from the onion yellows phytoplasma (OY).
      The identification of this gene and the previously reported genes encoding SecA
      and SecY provides evidence that the Sec system exists in phytoplasma. In
      addition, a gene encoding an antigenic membrane protein (Amp) (a type of
      immunodominant membrane protein) of OY was cloned and sequenced. The OY amp gene
      consisted of 702 nt encoding a protein of 233 aa which was highly similar to Amp
      of aster yellows phytoplasma (AY). Part of OY Amp was overexpressed in
      Escherichia coli, purified, and used to raise an anti-Amp polyclonal antibody.
      The anti-Amp antibody reacted specifically with an OY-infected plant extract in
      Western blot analysis and was therefore useful for the detection of OY as well as
      Amp. Amp has a conserved protein motif that is known to be exported by the Sec
      system of E. coli. A partial OY Amp protein expressed in E. coli was localized in
      the periplasm as a shorter, putatively processed form of the protein. It had
      probably been exported from the cytoplasm to the periplasm through the Sec
      system. Moreover, OY Amp protein expressed in OY and detected in OY-infected
      plants was apparently also processed. Because phytoplasmas cannot be cultured or
      transformed, little information is available regarding their protein secretion
      systems. This study suggests that the Sec system operates in this phytoplasma to
      export OY Amp.

PMID- 14702408
TI  - Analysis of geospecific markers for Helicobacter pylori variants in patients from
      Japan and Nigeria by triple-locus nucleotide sequence typing.
AB  - Human migrations and geographical separation over long periods may have resulted
      in ecologically distinct populations of Helicobacter pylori infecting individuals
      in different continents. This study used nucleotide sequence analysis with the
      aim of defining population-specific genomic motifs in isolates from East Asian
      and African dyspeptic patients. Sequences of internal fragments (542-627 bp) of
      three housekeeping genes (ureI, ahpC and atpA) were analysed for 85 isolates from
      individuals in Japan and China (30 isolates), Nigeria and South Africa (14
      isolates), the United Kingdom (32 isolates), and nine miscellaneous reference
      strains. Phylogenetic analyses showed a high degree of intra-set relatedness
      amongst sequences from the Japanese and Nigerian isolates, with each robustly
      segregated as distinct lineages irrespective of cagA presence and vacA allelic
      type. All strains had unique combined sequence types except for identical paired
      (antrum/corpus) isolates. Population-specific polymorphisms were identified
      within each gene which were combined to provide unique motifs defining the
      Japanese and Nigerian regional populations. The alleles were present at variable
      frequencies in UK and South African isolates. The findings provide unique
      evidence of positive selection for conserved nucleotide sites linked to the
      geographical separation in Japan of a strain subpopulation for which we propose
      the designation H. pylori geovar 'orientalis'.

PMID- 14702409
TI  - Functional relationship between SpoVIF and GerE in gene regulation during
      sporulation of Bacillus subtilis.
AB  - The sporulation-specific SpoVIF (YjcC) protein of Bacillus subtilis is essential
      for the development of heat-resistant spores. The GerE protein, the smallest
      member of the LuxR-FixJ family, contains a helix-turn-helix (HTH) motif and is
      involved in the expression of various sporulation-specific genes. In this study,
      the gene expression and protein composition of sporulating spoVIF-negative cells
      were analysed. CgeA, CotG and CotS, which are GerE-dependent coat proteins, were
      not expressed in the spoVIF-negative cells. Northern blotting showed that SpoVIF
      regulated the transcription of cgeA, cotG and cotS in a manner similar to that of
      GerE. In spoVIF-negative cells, gerE mRNA was transcribed normally, but
      immunoblot analysis using anti-GerE antiserum showed that the quantity of GerE
      protein was considerably less than that in wild-type controls. Using GFP (green
      fluorescent protein) fusion proteins, the localization of SpoVIF and GerE was
      observed by fluorescence microscopy. SpoVIF-GFP was detectable in the mother cell
      compartment, as was GerE-GFP. These results suggest that SpoVIF directly or
      indirectly controls the function of the GerE protein, and that SpoVIF is required
      for gene regulation during the latter stages of sporulation.

PMID- 14702410
TI  - Demonstration of antifreeze protein activity in Antarctic lake bacteria.
AB  - Antifreeze proteins (AFPs) are a structurally diverse group of proteins that have
      the ability to modify ice crystal structure and inhibit recrystallization of ice.
      AFPs are well characterized in fish and insects, but very few bacterial species
      have been shown to have AFP activity to date. Thirty eight freshwater to
      hypersaline lakes in the Vestfold Hills and Larsemann Hills of Eastern Antarctica
      were sampled for AFPs during 2000. Eight hundred and sixty six bacterial isolates
      were cultivated. A novel AFP assay, designed for high-throughput analysis in
      Antarctica, demonstrated putative activity in 187 of the cultures. Subsequent
      analysis of the putative positive isolates showed 19 isolates with significant
      recrystallization inhibition (RI) activity. The 19 RI active isolates were
      characterized using ARDRA (amplified rDNA restriction analysis) and 16S rDNA
      sequencing. They belong to genera from the alpha- and gamma-Proteobacteria, with
      genera from the gamma-subdivision being predominant. The 19 AFP-active isolates
      were isolated from four physico-chemically diverse lakes. Ace Lake and Oval Lake
      were both meromictic with correspondingly characteristic chemically stratified
      water columns. Pendant Lake was a saline holomictic lake with different chemical
      properties to the two meromictic lakes. Triple Lake was a hypersaline lake rich
      in dissolved organic carbon and inorganic nutrients. The environments from which
      the AFP-active isolates were isolated are remarkably diverse. It will be of
      interest, therefore, to elucidate the evolutionary forces that have led to the
      acquisition of functional AFP activity in microbes of the Vestfold Hills lakes
      and to discover the role the antifreezes play in these organisms.

PMID- 14702411
TI  - Temperature and growth-phase effects on Aeromonas hydrophila survival in natural
      seawater microcosms: role of protein synthesis and nucleic acid content on viable
      but temporarily nonculturable response.
AB  - The behaviour of Aeromonas hydrophila in nutrient-poor filter-sterilized seawater
      was investigated at 23 and 5 degrees C with respect to its growth phase. At both
      temperatures, the culturable A. hydrophila population declined below the
      detection level (0.1 c.f.u. ml(-1)) after 3-5 weeks, depending on the initial
      physiological state of the cells. During the first week, starved A. hydrophila
      cells appeared more resistant to the seawater stress at 5 degrees C than cells
      initially in the exponential growth phase. This difference was not observed at 23
      degrees C, where de novo protein synthesis seemed to be required for long-term
      adaptation of cells from the exponential growth phase. Over the duration of the
      experiments, intact and total cell concentrations were not significantly
      affected, indicating that bacteria had entered a so-called viable but
      nonculturable state (VBNC). However, the incubated bacteria rapidly became
      heterogeneous with respect to their nucleic acid content, and their cell size
      decreased faster at 23 than at 5 degrees C. Resuscitation of VBNC cells was
      attempted by a temperature shift from 5 to 23 degrees C without exogenous
      nutrient addition. Comparison of the growth rates of the stressed population and
      of the untreated bacteria growing in the same autoclaved initial cell suspension
      showed significantly faster growth for the stressed cells, suggesting that in
      addition to growth of the few culturable stressed cells, a proportion of injured
      cells became culturable.

PMID- 14702412
TI  - The csp operon of Streptococcus salivarius encodes two predicted cell-surface
      proteins, one of which, CspB, is associated with the fimbriae.
AB  - A Tn917 mutant library was generated to identify genes involved in the biogenesis
      of Streptococcus salivarius fimbriae. A fimbria-deficient mutant was isolated by
      negative selection using an immunomagnetic separation technique with specific
      anti-fimbriae polyclonal antibodies (pAbs). The transposon was inserted in an
      ORF, called orf176, which encoded a protein of unknown function. The transposon
      prevented the transcription of orf176 as well as two genes located downstream,
      which are designated cspA and cspB and which form the csp operon. Sequence
      analyses of CspA and CspB revealed that both proteins possessed the classic cell
      wall-anchoring motif (LPXTG) of Gram-positive bacterial surface proteins.
      Recombinant CspA (rCspA) and CspB (rCspB) proteins were generated in Escherichia
      coli and used to produce pAbs. Immunolocalization experiments showed that anti
      rCspB, but not anti-rCspA antibodies specifically recognized S. salivarius
      fimbriae. Our results suggested that the csp operon encoded predicted cell
      surface proteins, one of which, CspB, was associated with the fimbriae.

PMID- 14702413
TI  - A polymorphic tandem repeat potentially useful for typing in the chromosome of
      Yersinia enterocolitica.
AB  - The hexanucleotide CCAGCA was found repeated 15 times in tandem on the 5' side of
      the virginiamycin acetyl transferase gene of Yersinia enterocolitica strain Y56.
      The corresponding region was analysed by PCR from 54 clinical strains belonging
      to the same biotype and serotype, and others from this laboratory collection
      belonging to different biotypes and serotypes. Each strain produced a single
      amplification product whose size was variable among strains, revealing that the
      locus was polymorphic. Nucleotide sequence determination of selected PCR products
      showed that the polymorphism was due to the precise expansion or reduction in the
      number of hexanucleotide repeats. Analysis of this locus in a few strains showing
      the same PFGE pattern showed that it was also polymorphic. These results suggest
      that this method could be valuable to increase the discriminatory power of
      current Y. enterocolitica typing schemes.

PMID- 14702414
TI  - Chlamydia trachomatis sigma28 recognizes the fliC promoter of Escherichia coli
      and responds to heat shock in chlamydiae.
AB  - The rpsD gene of Chlamydia trachomatis encodes the alternative sigma factor
      sigma28, which bears strong homology to many bacterial sigma factors, including
      Escherichia coli sigma8 and Bacillus subtilis sigmaB and sigmaD. Recently, a
      sigma28 promoter was identified upstream of the late-cycle-expressed gene hctB,
      which encodes the Chlamydia-histone-like protein 2 (Yu & Tan, 2003). In this
      study it is shown that the product of chlamydial rpsD is an E. coli sigma28
      homologue. It was found that recombinant chlamydial sigma8, in combination with
      E. coli core RNA polymerase, initiates transcription in vitro from the E. coli
      sigma28-dependent promoter of fliC. It was also demonstrated that the recombinant
      chlamydial sigma28 does not recognize major sigma factor sigma70-consensus-like
      sequences in vitro. In C. trachomatis-infected cells, two rpsD transcripts were
      detected with 5' ends located 18 (transcript I) and 54 bp (transcript II)
      upstream of the translational initiation codon at 16 and 30 h post-infection.
      When the temperature of cultures infected with C. trachomatis was shifted from 35
      to 42 degrees C, the rpsD transcript I increased dramatically. The levels of
      chlamydial sigma28, relative to EF-Tu, were greater throughout the exponential
      growth phase of the reticulate body, but lower late in the developmental cycle.
      These data support the hypothesis that sigma28 plays a role in the regulatory
      network that allows chlamydiae to survive changes in its environment, enabling it
      to complete its unique developmental cycle.

PMID- 14702415
TI  - The role and regulation of the extracellular proteases of Staphylococcus aureus.
AB  - Staphylococcus aureus has several extracellular proteases with proposed roles in
      virulence. SspA (serine protease), SspB (cysteine protease) and Aur
      (metalloprotease) have been characterized previously and SspA and SspB were found
      to be cotranscribed. The coding region for the cysteine protease ScpA has been
      identified and characterized. It is in a probable bi-cistronic operon with scpA
      located immediately upstream of a coding region for a 108 aa protein that is a
      specific inhibitor of ScpA. Using primer extension analysis promoters have been
      mapped and it was found that sigmaA is the only sigma factor involved in the
      transcription of scpA, sspABC and aur. The transcription of all the genes occurs
      maximally at post-exponential phase, being positively regulated by agr (accessory
      gene regulator) and negatively regulated by sarA (staphylococcal accessory
      regulator). Furthermore sigmaB represses transcription from the aur and scp
      operons similarly to the previously shown effect on ssp [Horsburgh, M., Aish, J.,
      White, I., Shaw, L., Lithgow, J. & Foster, S. (2002). J Bacteriol 184, 5457
      5467]. Using mutations in each protease gene the proteolytic cascade of
      activation has been analysed. Aur, SspA, SspB and ScpA are all produced as
      zymogens, activated by proteolytic cleavage. Although the metalloprotease, Aur,
      does catalyse activation of the SspA zymogen, it is not the sole agent capable of
      conducting this process. Site-directed mutagenesis revealed that Aur is not
      capable of undergoing auto-proteolysis to achieve activation. The cysteine
      protease, ScpA, appears to reside outside this cascade of activation, as mature
      ScpA was observed in the aur, sspA and sspB mutant strains. Using a mouse abscess
      model, it has been shown that insertional inactivation of sspA or sspB results in
      significant attenuation of virulence, whilst mutations in aur or scpA do not. It
      is likely the attenuation observed in the sspA strain is due to polarity on the
      sspB gene.

PMID- 14702416
TI  - Deletion of the NOT4 gene impairs hyphal development and pathogenicity in Candida
      albicans.
AB  - The Candida albicans NOT4 gene was disrupted in order to investigate the role of
      Not4p in growth, morphogenesis and pathogenicity. Heterozygote (NOT4/not4), null
      (not4/not4) and reconstructed heterozygote ([NOT4]/not4) strains of C. albicans,
      as well as CAF2-1, the parental strain, were grown under conditions that promote
      hyphal formation. When cultured in liquid medium 199 the heterozygote,
      reconstructed and wild-type strains began the yeast-to-hyphal transition within 3
      h and continued hyphal growth for the duration of experiments. The null mutant
      also began hyphal growth within 3-5 h but hyphae tended to be shorter and
      distorted. Subsequently, hyphal growth was arrested and growth returned
      predominantly to the yeast form. Similar differences were observed when strains
      were grown on solid Spider medium and medium 199. The parental, heterozygote and
      reconstructed strains formed normal filamentous networks emanating from colonies.
      In contrast, the null mutant failed to form hyphae on all solid media tested. The
      ability of the NOT4 null strain to form biofilms was also investigated, and it
      was observed that biofilm development does not readily occur for this strain.
      Virulence of each strain was examined utilizing the mouse model of systemic
      candidiasis. Mice infected with CAF2-1 succumbed to infection within 3-7 days.
      All mice infected with the null strain survived for the duration of experiments,
      while the heterozygote and reconstructed heterozygote strains showed an
      intermediate level of virulence. These findings suggest that NOT4 may play a role
      in affecting strain pathogenicity, possibly by regulating expression of certain
      genes that effect cellular morphogenesis and virulence.

PMID- 14702417
TI  - Intracellular autoregulation of the Mycobacterium tuberculosis PrrA response
      regulator.
AB  - Two-component systems are major regulatory systems for bacterial adaptation to
      environmental changes. During the infectious cycle of Mycobacterium tuberculosis,
      adaptation to an intracellular environment is critical for multiplication and
      survival of the micro-organism within the host. The M. tuberculosis prrA gene,
      encoding the regulator of the two-component system PrrA-PrrB, has been shown to
      be induced upon macrophage phagocytosis and to be transiently required for the
      early stages of macrophage infection. In order to study the mechanisms of
      regulation of the PrrA-PrrB two-component system, PrrA and the cytoplasmic part
      of the PrrB histidine kinase were produced and purified as hexahistidine-tagged
      recombinant proteins. Electrophoretic mobility shift assays indicated that PrrA
      specifically binds to the promoter of its own operon, with increased affinity
      upon phosphorylation. Moreover, induction of fluorescence was observed after
      phagocytosis of a wild-type M. tuberculosis strain containing the gfp reporter
      gene under the control of the prrA-prrB promoter, while this induction was not
      seen in a prrA/B mutant strain containing the same construct. These results
      indicate that the early intracellular induction of prrA depends on the
      autoregulation of this two-component system.

PMID- 14702418
TI  - Aggregation of heat-shock-denatured, endogenous proteins and distribution of the
      IbpA/B and Fda marker-proteins in Escherichia coli WT and grpE280 cells.
AB  - Submission of wild-type Escherichia coli to heat shock causes an aggregation of
      cellular proteins. The aggregates (S fraction) are separable from membrane
      fractions by ultracentrifugation in a sucrose density gradient. In contrast, no
      protein aggregation was detectable in an E. coli grpE280 mutant either by this
      technique or by electron microscopy. In search of an explanation for this
      observation at a molecular level, two kinds of marker proteins were used: Fda
      (fructose-1,6-biphosphate aldolase), the previously identified S fraction
      component, and IbpA/B, small heat-shock proteins abundantly associated with the S
      fraction proteins. Both types of marker proteins, normally never found in the
      outer-membrane (OM) fraction of WT cells, were present in the OM fraction from
      grpE cells after heat shock. This pointed to the presence of aggregates smaller
      than those in WT cells that cosedimented with the OM fraction. The OM fraction
      was enlarged in grpE cells. Although not proven directly, the presence of still
      smaller aggregates, not exceeding the solubility level and containing inactive
      Fda, was noted in the soluble CP fraction containing the cytoplasmic and
      periplasmic proteins. Therefore, aggregation occurred in both strains, but in a
      different way. The autoregulation of the heat-shock response causes a greater
      increase of DnaK/DnaJ and IbpAB levels in grpE cells than in WT after temperature
      elevation. This may explain the prevalence of the small-sized aggregates in the
      grpE cells. Estimation of total Fda protein before and after heat shock did not
      show any loss. This indicated that renaturation rather than proteolysis underlies
      the final disappearance of the aggregates. Though surprising at first, this is
      not contradictory with the participation of heat-shock proteases in removal of
      protein components of the S fraction as shown before, since proteins that are
      irreversibly denatured are probably substrates for the proteases.

PMID- 14702419
TI  - Patency and the pump--the risks and benefits of off-pump CABG.

PMID- 14702420
TI  - From asthma to atherosclerosis--5-lipoxygenase, leukotrienes, and inflammation.

PMID- 14702421
TI  - Advance care planning.

PMID- 14702422
TI  - The new Medicare prescription-drug legislation.

PMID- 14702423
TI  - Once-daily valacyclovir to reduce the risk of transmission of genital herpes.
AB  - BACKGROUND: Nucleoside analogues against herpes simplex virus (HSV) have been
      shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and
      may prevent sexual transmission of HSV. METHODS: We followed 1484
      immunocompetent, heterosexual, monogamous couples: one with clinically
      symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2
      infection were randomly assigned to receive either 500 mg of valacyclovir once
      daily or placebo for eight months. The susceptible partner was evaluated monthly
      for clinical signs and symptoms of genital herpes. Source partners were followed
      for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2
      mucosal shedding. Both partners were counseled on safer sex and were offered
      condoms at each visit. The predefined primary end point was the reduction in
      transmission of symptomatic genital herpes. RESULTS: Clinically symptomatic HSV-2
      infection developed in 4 of 743 susceptible partners who were given valacyclovir,
      as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent
      confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was
      observed in 14 of the susceptible partners who received valacyclovir (1.9
      percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio,
      0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected
      in samples of genital secretions on 2.9 percent of the days among the HSV-2
      infected (source) partners who received valacyclovir, as compared with 10.8
      percent of the days among those who received placebo (P<0.001). The mean rates of
      recurrence were 0.11 per month and 0.40 per month, respectively (P<0.001).
      CONCLUSIONS: Once-daily suppressive therapy with valacyclovir significantly
      reduces the risk of transmission of genital herpes among heterosexual, HSV-2
      discordant couples.

PMID- 14702424
TI  - A randomized comparison of off-pump and on-pump multivessel coronary-artery
      bypass surgery.
AB  - BACKGROUND: The effect of the use of coronary-artery bypass surgery without
      cardiopulmonary bypass and cardiac arrest ("off pump") on graft patency remains
      uncertain. We undertook a prospective, randomized, controlled study to compare
      graft-patency rates and clinical outcomes in off-pump surgery with conventional,
      "on-pump" surgery. METHODS: We randomly assigned 50 patients to undergo on-pump
      coronary-artery bypass grafting and 54 to undergo off-pump surgery. Surgical and
      anesthetic techniques were standardized for both groups. Clinical outcomes and
      troponin T levels were measured. Three months later, the patients underwent
      coronary angiography, including quantitative analysis. RESULTS: The mean age of
      the patients was 63 years, and 87 percent were men. The on-pump group received a
      mean of 3.4 grafts, and the off-pump group 3.1 (P=0.41). There were no deaths.
      There was no significant difference in the median postoperative length of stay
      between the two groups (seven days in each group). The area under the curve of
      troponin T levels was higher during the first 72 hours in the on-pump group than
      in the off-pump group (30.96 hr x microg per liter vs. 19.33 hr x microg per
      liter, P=0.02). At three months, 127 of 130 grafts were patent in the on-pump
      group (98 percent), as compared with 114 of 130 in the off-pump group (88
      percent, P=0.002). The patency rate was higher for all graft territories in the
      on-pump group than in the off-pump group. CONCLUSIONS: In this randomized study,
      off-pump coronary surgery was as safe as on-pump surgery and caused less
      myocardial damage. However, the graft-patency rate was lower at three months in
      the off-pump group than in the on-pump group, and this difference has
      implications with respect to the long-term outcome.

PMID- 14702425
TI  - Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and
      atherosclerosis.
AB  - BACKGROUND: Leukotrienes are inflammatory mediators generated from arachidonic
      acid (polyunsaturated n-6 fatty acid) by the enzyme 5-lipoxygenase. Since
      atherosclerosis involves arterial inflammation, we hypothesized that a
      polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis
      in humans and that this effect could interact with the dietary intake of
      competing 5-lipoxygenase substrates. METHODS: We determined 5-lipoxygenase
      genotypes, carotid-artery intima-media thickness, and markers of inflammation in
      a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los
      Angeles Atherosclerosis Study. Dietary arachidonic acid and marine n-3 fatty
      acids (including a competing 5-lipoxygenase substrate that reduces the production
      of inflammatory leukotrienes) were measured with the use of six 24-hour recalls
      of food intake. RESULTS: Variant 5-lipoxygenase genotypes (lacking the common
      allele) were found in 6.0 percent of the cohort. Mean (+/-SE) intima-media
      thickness adjusted for age, sex, height, and racial or ethnic group was increased
      by 80+/-19 microm (95 percent confidence interval, 43 to 116; P<0.001) among
      carriers of two variant alleles, as compared with carriers of the common (wild
      type) allele. In multivariate analysis, the increase in intima-media thickness
      among carriers of two variant alleles (62 microm, P<0.001) was similar in this
      cohort to that associated with diabetes (64 microm, P=0.01), the strongest common
      cardiovascular risk factor. Increased dietary arachidonic acid significantly
      enhanced the apparent atherogenic effect of genotype, whereas increased dietary
      intake of n-3 fatty acids blunted the effect. Finally, the plasma level of C
      reactive protein, a marker of inflammation, was increased by a factor of 2 among
      carriers of two variant alleles as compared with that among carriers of the
      common allele. CONCLUSIONS: Variant 5-lipoxygenase genotypes identify a
      subpopulation with increased atherosclerosis. The observed diet-gene interactions
      further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas
      marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to
      atherosclerosis in this subpopulation.

PMID- 14702426
TI  - Clinical practice. Acute infectious diarrhea.

PMID- 14702427
TI  - Diabetic retinopathy.

PMID- 14702429
TI  - Clinical problem-solving. True, true, and related.

PMID- 14702430
TI  - Use of antiviral drugs to prevent herpesvirus transmission.

PMID- 14702431
TI  - Dissatisfaction with medical practice.

PMID- 14702432
TI  - Early Alzheimer's disease.

PMID- 14702433
TI  - Suspected pulmonary embolism.

PMID- 14702434
TI  - Pneumococcal conjugate vaccine in children.

PMID- 14702435
TI  - The charitable trust as a model for genomic biobanks.

PMID- 14702436
TI  - Staging of lung cancer with integrated PET-CT.

PMID- 14702437
TI  - More on pseudohypocalcemia and gadolinium-enhanced MRI.

PMID- 14702438
TI  - Multifocal myoclonus induced by trimethoprim-sulfamethoxazole therapy in a
      patient with nocardia infection.

PMID- 14702439
TI  - Using telemedicine to provide pediatric subspecialty care to children with
      special health care needs in an underserved rural community.
AB  - OBJECTIVE: For children with special health care needs (CSHCN) that live in
      rural, medically underserved communities, obtaining subspecialty care is a
      challenge. Telemedicine is a means of improving access to these children by
      addressing rural physician shortages and geographic barriers. This article
      reports a medical-needs assessment of parents/guardians with CSHCN and the status
      of a telemedicine program for CSHCN as well as the results of parent/guardian and
      local provider satisfaction with the telemedicine program. DESIGN: We report the
      results of a pretelemedicine medical-needs survey conducted in March 1999 by
      using a convenience sample of CSHCN living in a rural, medically underserved
      community located 90 miles north of the University of California Davis Children's
      Hospital (Davis, CA). In April 1999, a telemedicine program was initiated to
      provide consultations to CSHCN and has continued since. We also report the
      parent/guardian's perceptions of the appropriateness and quality of telemedicine
      consultations and the local provider's satisfaction with telemedicine
      consultations completed from April 1999 to April 2002. RESULTS: The
      pretelemedicine medical-needs assessment demonstrated several barriers in access
      to subspecialty care including traveling >1 hour for appointments (86% of
      parents/guardians), missing work for appointments (96% of working
      parents/guardians), and frequently relying on emergency department services
      and/or self-regulation of their child's medications. From April 1999 to April
      2002, 130 telemedicine consultations were completed on 55 CSHCN. Overall,
      satisfaction was very high. All the parents/guardians rated satisfaction with
      telemedicine care as either "excellent" or "very good," and all but 2 of the
      rural providers' surveys reported satisfaction with telemedicine as "excellent"
      or "very good." The frequency of telemedicine consultations has increased with
      time. CONCLUSIONS: Pediatric subspecialty telemedicine consultations can be
      provided to CSHCN living in a rural, medically underserved community with high
      satisfaction among local providers and parents/guardians. Telemedicine should be
      considered as a means of facilitating care to CSHCN that, relative to the
      customary delivery of health care, is more accessible, family-centered, and
      coordinated among patients and their health care providers.

PMID- 14702440
TI  - Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in
      children with severe sepsis.
AB  - OBJECTIVE: In a phase 3 trial, recombinant human activated protein C (drotrecogin
      alfa [activated]) significantly reduced mortality in adult patients with severe
      sepsis. We have now performed a preliminary analysis of the safety,
      pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in
      pediatric patients with severe sepsis. DESIGN AND SETTING: Open-label,
      nonrandomized, sequential, 2-part study conducted in 11 medical centers in the
      United States and United Kingdom. PATIENTS: Eighty-three pediatric patients with
      severe sepsis aged term newborn (>or=38 weeks' gestation) to <18 years old.
      INTERVENTION: In part 1, drotrecogin alfa (activated) was administered as
      escalating doses of 6, 12, 24, and 36 micro g/kg per hour for 6 hours for each
      patient (n = 21). In part 2, drotrecogin alfa (activated) was infused at a rate
      of 24 micro g/kg per hour for 96 hours in 62 patients. MAIN OUTCOME MEASURES:
      Plasma clearance, plasma concentration, D-dimer, protein C, and antithrombin
      levels were measured, and adverse events were monitored. RESULTS: The trial
      enrolled 83 pediatric patients with severe sepsis, aged term newborn (>or=38
      weeks' gestation) to <18 years. In part 1, a dose of 24 micro g/kg per hour
      produced steady-state plasma concentrations of activated protein C similar to
      those attained in equivalently dosed adult severe sepsis patients. For all
      pediatric patients dosed at 24 micro g/kg per hour, the median weight-normalized
      clearance was 0.45 L/hour/kg and the median steady-state concentration was 51.3
      ng/mL. The mean plasma half-life was 30 minutes. Weight-normalized clearance in
      pediatric and adult patients did not differ significantly with age or weight. D
      dimer levels decreased 26% from baseline to end of infusion. Baseline levels of
      protein C and antithrombin increased 79% and 24%, respectively, over the 96-hour
      treatment period in part 2. The incidence of serious bleeding during infusion and
      during the entire study period was 2.4% and 4.8%, respectively. CONCLUSIONS:
      Pediatric patients with severe sepsis manifest sepsis-induced coagulopathy
      including protein C deficiency comparable to that seen in adults with severe
      sepsis. The pharmacokinetics, pharmacodynamic effects, and safety profile of
      drotrecogin alfa (activated) in pediatric patients are similar to those
      previously published for adult patients. A large, phase 3, randomized, placebo
      controlled study is ongoing to confirm these results and formally assess the
      safety and efficacy of drotrecogin alfa (activated) in children.

PMID- 14702441
TI  - The effect of hospital volume of pediatric appendectomies on the misdiagnosis of
      appendicitis in children.
AB  - BACKGROUND: Although appendicitis is a common pediatric surgical condition, it is
      often misdiagnosed. Because higher hospital volume has been associated with
      improved outcome for many surgical procedures, the current study investigates
      whether hospital volume of pediatric appendectomies is associated with
      misdiagnosis of appendicitis in children. METHODS: The Kids' Inpatient Database
      is a national sample of pediatric discharges from 2521 hospitals in 22 states in
      1997. In this study, misdiagnosis was defined as a patient with a principal
      International Classification of Diseases, Ninth Revision procedure code for
      nonincidental appendectomy without a corresponding diagnosis code for
      appendicitis. Hospitals were stratified into 5 groups based on the number of
      nonincidental appendectomies performed on children in 1997: lowest (<1 per
      month), low (>or=1 per month but <1 per week), medium (1-2 per week), high (2-3
      per week), and highest (>or=3 per week). Using generalized estimating equations
      to control for clustering within hospitals, we developed a logistic regression
      model of the effect of hospital volume on misdiagnosis while adjusting for
      patient age, gender, race, and insurance status. RESULTS: In the database, 37,109
      nonincidental appendectomies were performed on children 1 to 18 years old in
      1997. Of those, 3103 (8.4%) were misdiagnosed. Of all appendectomies, 24,655
      (66.4%) were performed at lowest- or low-volume hospitals. After adjusting for
      patient characteristics, lowest- (odds ratio [OR]: 1.5; 95% confidence interval
      [CI]: 1.0-2.2) and low- (OR: 1.6; 95% CI: 1.1-2.3) volume hospitals had a
      significantly increased likelihood of misdiagnosis compared with highest-volume
      hospitals. Misdiagnosis at medium- (OR: 1.5; 95% CI: 1.0-2.2) and high- (OR: 1.4;
      95% CI: 0.9-2.2) volume hospitals was similar to misdiagnosis at lower-volume
      hospitals, although not statistically different from highest-volume hospitals.
      CONCLUSIONS: Almost two thirds of pediatric appendectomies are performed at
      hospitals performing <1 pediatric appendectomy per week. Lower hospital volume of
      pediatric appendectomies is associated with a significantly increased likelihood
      of misdiagnosis of appendicitis in children.

PMID- 14702442
TI  - Selective imaging strategies for the diagnosis of appendicitis in children.
AB  - BACKGROUND: We previously reported an appendiceal imaging protocol in which
      children with equivocal clinical presentations for acute appendicitis undergo
      ultrasonography (US) followed by computed tomography (CT). However, risk groups
      of children who would benefit most from imaging studies have not been
      established. OBJECTIVE: To define and test selective imaging guidelines to
      increase diagnostic accuracy and reduce unnecessary testing for children with
      suspected appendicitis. METHODS: We modeled outcomes under 3 different management
      guidelines. Patients were risk-stratified by a recursive partitioning analysis of
      a retrospective cohort. Subjects included children with equivocal presentations
      of acute appendicitis evaluated between January 1996 and December 1999. By using
      recursive partitioning, 3 risk groups were identified: low, medium, and high risk
      for acute appendicitis. Three imaging guidelines were defined. Under the first
      guideline, representing standard clinical practice at Children's Hospital Boston
      at the time of the study, all children with equivocal signs and symptoms for
      acute appendicitis undergo US first. If the US is positive, the child proceeds to
      appendectomy. If the US is negative, the child undergoes CT. Under guideline 2,
      low-risk children undergo US and, if negative, are discharged from the hospital.
      High-risk children undergo CT, and medium-risk children undergo US followed by
      CT. Under the third guideline, low-risk children undergo no imaging and are
      admitted for observation. High-risk children proceed directly to appendectomy
      without imaging studies. Medium-risk children undergo US followed by CT. Clinical
      outcomes and the number of imaging studies performed were modeled under current
      practice and under each guideline. RESULTS: Identified were 1401 cases of
      equivocal appendicitis; 958 (68.4%) with complete data. The mean age was 11 +/-
      4.3 years. Of 958 children, 588 (61.4%) had acute appendicitis. One hundred forty
      three patients were in the low-risk group, defined as neutrophils <or=67%, bands
      <5%, and no guarding on abdominal examination. Fifteen (10%) children had
      appendicitis. Two hundred twenty-five were high-risk for appendicitis defined as
      neutrophils >67%, white blood cell count >10,000/mm(3), guarding, and abdominal
      pain >13 hours. Of these, 202 (90%) had appendicitis. Under guideline 1, there
      were 22 negative appendectomies, 35 missed or delayed diagnoses, and 958 USs and
      673 CT scans performed. Under guideline 2, there would have been 23 negative
      appendectomies, 36 missed or delayed diagnoses, and 733 USs and 637 CT scans
      performed. Under guideline 3, there would have been 36 negative appendectomies,
      37 missed or delayed diagnoses, and 590 USs and 412 CT scans performed.
      CONCLUSIONS: Selective imaging guidelines can reduce the number of radiographic
      studies performed with minimal diminution in accuracy of diagnosis of pediatric
      appendicitis.

PMID- 14702443
TI  - The diagnosis of appendicitis in children: outcomes of a strategy based on
      pediatric surgical evaluation.
AB  - OBJECTIVE: To determine the accuracy of a protocol for diagnosis of appendicitis
      in children based on clinical evaluation by a pediatric surgeon with selective
      use of diagnostic imaging studies. We performed this study because 1) current
      reports in the medical, pediatric, emergency medical, and surgical literature
      advocate imaging, particularly computed tomography (CT), as the gold standard for
      diagnosis of appendicitis, and 2) the value of pediatric surgical evaluation
      early in the management of the child with possible appendicitis has rarely been
      emphasized. METHODS, DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of
      356 children (mean age: 9.6 years; range: 1-18 years) referred to a regional
      pediatric surgical center for possible appendicitis from 1999 through 2001.
      INTERVENTIONS: Initial pediatric surgical evaluation consisted of history,
      physical examination, white blood cell count, differential count, and urinalysis.
      Children diagnosed with appendicitis underwent appendectomy without additional
      studies; those with equivocal findings received intravenous fluids, rest, and
      reevaluation after 4 to 6 hours. Imaging was used selectively by the pediatric
      surgeon. OUTCOME MEASURES: Sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of the protocol based on final diagnoses;
      rate of appendiceal perforation; and rate of negative appendectomy. RESULTS: Of
      356 children evaluated for appendicitis, 220 (62%) had an appendectomy. Two
      hundred nine (95%) had histologically proven appendicitis, and 11 (5%) had a
      normal appendix. Of the 209 children with appendicitis, 139 (66%) had acute
      appendicitis, 34 (16%) had advanced appendicitis without perforation, and 36
      (17%) had advanced appendicitis with perforation. Appendectomy was performed
      after initial evaluation in 195 (89%) of the 220 children and after a period of
      supportive care and observation in 25 (11%) of 220. One hundred thirty-six
      children (38%) did not have an appendectomy and were discharged with other
      diagnoses. The sensitivity of this protocol was 99%, specificity was 92%,
      positive predictive value was 95%, and negative predictive value was 99%. The
      accuracy was 97% compared with an accuracy of 82% for ultrasound alone and 90%
      for CT scan alone. CONCLUSIONS: These data show that a protocol based on clinical
      evaluation by a pediatric surgeon with selective use of imaging was highly
      accurate for the diagnosis of appendicitis in children. Low rates of negative
      appendectomy (5%) and perforation (17%) were achieved without the potential costs
      and radiation exposure of excess imaging.

PMID- 14702444
TI  - The effect of birth hospital type on the outcome of very low birth weight
      infants.
AB  - OBJECTIVE: To test the hypothesis that the likelihood of death or major morbidity
      is reduced for very low birth weight (VLBW; <1500 g) infants who are born at
      hospitals with subspecialty perinatal and neonatal care compared with other
      available birth sites. METHODS: A population-based cohort study was conducted of
      all live births of 500 to 1499 g at the 19 hospitals in the greater Cincinnati
      region from September 1, 1995, through December 31, 1997 (N = 848). Primary
      outcome was the risk-adjusted, predischarge mortality or morbidity, including
      bronchopulmonary dysplasia, severe intracranial hemorrhage, severe retinopathy of
      prematurity, or necrotizing enterocolitis for VLBW infants who were born at
      subspecialty perinatal centers compared with those who were born at
      nonsubspecialty centers. RESULTS: The odds of death or major morbidity for VLBW
      infants who are born at nonsubspecialty perinatal centers is twice that of
      infants who are born at subspecialty centers despite controlling for demographic
      (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 1.7-4.2) and practice
      characteristics (OR: 1.96; 95% CI: 1.2-3.2). The effect of birth hospital type on
      death or major morbidity was greater for infants of 1000 to 1499 g birth weight
      (OR: 3.42; 95% CI: 2.0-6.1) than for infants of 500 to 999 g birth weight (OR:
      2.1; 95% CI: 1.0-4.8). CONCLUSION: The current study lends strong support to
      existing Academy of Pediatrics and American College of Obstetricians and
      Gynecologists recommendations that deliveries at <32 weeks' gestational age occur
      at subspecialty perinatal centers.

PMID- 14702445
TI  - Length-of-stay policies and ascertainment of postdischarge problems in newborns.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of an early
      postpartum discharge program and a subsequent legislative mandate for 48 hours of
      hospital coverage on incidence of newborn jaundice and feeding problems. We
      tested the hypothesis that heightened postdischarge ascertainment (rather than
      short stays) is responsible for apparent increases in these outcomes. METHODS:
      Interrupted time series analysis was conducted on retrospective data from the
      automated medical records of a large Massachusetts health maintenance
      organization (HMO). A population of 20,366 mother-infant pairs with normal
      vaginal deliveries between October 1990 and March 1998 was identified. The
      interventions included a new HMO protocol in 1994 of 1 hospital overnight after
      delivery, plus a nurse home visit, then the Massachusetts' 1996 minimum coverage
      law. Postpartum length of stay, clinical evaluation on day 3 or 4 of life, health
      center visits up to day 21, health center diagnoses of jaundice or feeding
      problems, bilirubin testing and test severity, rehospitalizations, and emergency
      department visits were measured. RESULTS: Postpartum stays <2 nights rose from
      28% of newborns before implementation of the program to 70% immediately after
      implementation. Later, this rate fell from 66% before the mandate to 21% just
      after the law went into effect. Day 3 or 4 evaluation rose from 24.5% to 64%
      after the program, then dropped somewhat to 53% after the mandate. Controlling
      for longer-term trends in health center visits, implementation of the early
      discharge program was associated with approximately 1 extra visit for every 4
      newborns within the first 21 days of life. The state mandate did not affect
      health center visit rates. Jaundice diagnoses were flat at 8% of newborns during
      the baseline, then rose to a constant 11% throughout the program and postmandate
      periods. Bilirubin testing of newborns also rose by 3.4 percentage points at the
      time of program implementation, and the proportion of tested newborns with
      results calling for at least consideration of phototherapy rose by 6 percentage
      points. Phototherapy use rose from a flat 1.8% to 2.4% of newborns after program
      implementation. Feeding problem diagnoses more than doubled at the time of
      program implementation and remained elevated after the mandate.
      Rehospitalizations overall and specifically for jaundice were constant over time,
      whereas more rare emergency department visits for jaundice dropped from 0.3% of
      newborns to 0 on program implementation. CONCLUSIONS: Sudden increases in
      jaundice-related measures and identification of infant feeding problems were not
      associated with changes in length of stay in this setting. Instead, these
      increases seem to be the result of more frequent evaluation of newborns during
      the critical day 3 to 4 period and may also have been elevated by a new climate
      of concern about neonatal vulnerability. "Ascertainment bias" may have confounded
      findings in previous reports that raised concerns about the safety of early
      discharge.

PMID- 14702446
TI  - Gastric residuals and their relationship to necrotizing enterocolitis in very low
      birth weight infants.
AB  - OBJECTIVE: To determine the characteristics of gastric residuals in very low
      birth weight (VLBW; <or=1500 g birth weight) infants with and without necrotizing
      enterocolitis (NEC). METHODS: Case-control study compared 51 VLBW infants who had
      proven NEC (pneumatosis intestinalis, portal venous gas, and/or perforation;
      excluding spontaneous gastrointestinal perforations) with 102 control subjects
      (without suspected or proven NEC) who were matched for birth weight, gestational
      age, race, and sex and were born January 1996 to December 2001. The age in days
      at diagnosis of NEC was identified in infants with NEC, and feeding
      characteristics were recorded for the previous 6 days. Feeding characteristics
      were recorded for control subjects for the corresponding time period. RESULTS:
      The median birth weight was 822 g and median gestational age was 26 weeks in both
      groups. Feeds were started on the fifth day, with a planned increase to full
      feeds over 10 days (median) in both groups. Median time to full feeds was 13 days
      in both groups. Median age of onset of NEC was day 24. The total residuals as a
      percentage of total feed volume (the primary outcome), maximum residual in the
      previous 6 days, maximum residual as a percentage of the feed, maximum residuals
      over the 6 days, and the percentage of feeds with residuals were higher in the
      NEC group. The maximum residual (median [25th-75th centiles]) was as follows:
      control subjects: 2 mL per feed (0.5-3.5) or 14% of a feed (4-33); NEC group: 4.5
      mL per feed (1.5-9.8) or 40% of a feed (24-61). The total residuals as percentage
      of feeds and the average of maximum residuals increased in the NEC group from the
      first 3 days to the 3 days before diagnosis of NEC, but a similar increase was
      not noted for control subjects. CONCLUSIONS: VLBW infants who developed NEC had
      more gastric residuals. However, there was overlap with the normal control
      subjects. Of the gastric residual data, the maximum residual seems to be the best
      predictor for NEC in the subsequent days.

PMID- 14702447
TI  - Influence of Helicobacter pylori eradication on gastroesophageal reflux symptoms
      and epigastric pain in children and adolescents.
AB  - OBJECTIVE: Conflicting reports have noted a possible association linking
      eradication of Helicobacter pylori with aggravation of gastroesophageal reflux
      (GER) disease. We prospectively evaluated the effect of eradication of H pylori
      on GER symptoms and epigastric pain and the association among these 3 parameters
      in a pediatric cohort. METHODS: Patients who were referred for gastroscopy were
      evaluated for frequency, severity, and nocturnal presence of symptoms related to
      GER as well as epigastric pain. Patients who were positive for H pylori received
      triple antibiotic therapy. The patients were followed for at least 6 months after
      therapy. Patients with successful eradication had symptoms compared with their
      pre-eradication state and were compared with a cohort of patients without H
      pylori or those with persistent H pylori. RESULTS: Of 119 children and
      adolescents who were recruited, 95 patients completed the study, with a mean
      follow-up of 11.2 months. The distribution of outcomes for each GER symptom
      (better, worse, unchanged) was similar before and after eradication and did not
      depend on prior H pylori status. Among patients with GER and epigastric pain,
      improvement in epigastric pain was significantly correlated with the improvement
      in GER symptoms but not with eradication of H pylori. CONCLUSIONS: Eradication of
      H pylori is not associated with increased symptoms of GER in children and
      adolescents. Improvement in epigastric pain in children is significantly
      correlated with the improvement in GER symptoms but not with eradication of H
      pylori.

PMID- 14702449
TI  - Computerized physician order entry and medication errors in a pediatric critical
      care unit.
AB  - OBJECTIVE: Medication errors are a major concern of health care professionals and
      medical institutions, especially errors involving children. Studies in adults
      have shown that computerized physician order entry (CPOE) systems reduce
      medication errors and adverse drug events (ADEs). The effect of CPOE
      implementation in a pediatric population has not been reported. The objective of
      this study was to evaluate the impact of CPOE on the frequency of errors in the
      medication ordering process in a pediatric critical care unit (PCCU). METHODS: A
      prospective trial was conducted of 514 pediatric patients who were admitted to a
      20-bed PCCU in a tertiary-care children's hospital before and after
      implementation of CPOE. Medication errors were identified after review of all
      orders during the study period and then further classified as potential ADEs,
      medication prescribing errors (MPE), and rule violations (RV). RESULTS: A total
      of 13 828 medication orders were reviewed. Before implementation, potential ADEs
      occurred at a rate of 2.2 per 100 orders, MPEs at a rate of 30.1 per 100 orders,
      and RVs at a rate of 6.8 per 100 orders. After implementation, the rate of
      potential ADEs was reduced to 1.3 per 100 orders, MPEs to 0.2 per 100 orders, and
      RVs to 0.1 per 100 orders. The overall error reduction was 95.9%. Potential ADEs
      were reduced by 40.9%, and MPEs and RVs were reduced by 99.4% and 97.9%,
      respectively. CONCLUSIONS: The implementation of CPOE resulted in almost a
      complete elimination of MPEs and RVs and a significant but less dramatic effect
      on potential ADEs.

PMID- 14702450
TI  - An evaluation of information-seeking behaviors of general pediatricians.
AB  - OBJECTIVE: Usage of computer resources at the point of care has a positive effect
      on physician decision making. Pediatricians' information-seeking behaviors are
      not well characterized. The goal of this study was to characterize quantitatively
      the information-seeking behaviors of general pediatricians and specifically
      compare their use of computers, including digital libraries, before and after an
      educational intervention. METHODS: General pediatric residents and faculty at a
      US Midwest children's hospital participated. A control (year 1) versus
      intervention group (year 2) research design was implemented. Eligible
      pediatrician pools overlapped, such that some participated first in the control
      group and later as part of the intervention. The intervention group received a 10
      minute individual training session and handout on how to use a pediatric digital
      library to answer professional questions. A general medical digital library was
      also available. Pediatricians in both the control and the intervention groups
      were surveyed using the critical incident technique during 2 6-month time
      periods. Both groups were telephoned for 1- to 2-minute interviews and were
      asked, "What pediatric question(s) did you have that you needed additional
      information to answer?" The main outcome measures were the differences between
      the proportion of pediatricians who use computers and digital libraries and a
      comparison of the number of times that pediatricians use these resources before
      and after intervention. RESULTS: A total of 58 pediatricians were eligible, and
      52 participated (89.6%). Participant demographics between control (N = 41; 89.1%)
      and intervention (N = 31; 70.4%) were not statistically different. Twenty
      pediatricians were in both groups. Pediatricians were slightly less likely to
      pursue answers after the intervention (94.7% vs 89.2%); the primary reason cited
      for both groups was a lack of time. The pediatricians were as successful in
      finding answers in each group (95.7% vs 92.7%), but the intervention group took
      significantly less time (8.3 minutes vs 19.6 minutes). After the intervention,
      pediatricians used computers and digital libraries more to answer their questions
      and spent less time using them. CONCLUSION: This study showed higher rates of
      physician questions pursued and answered and higher rates of computer use at
      baseline and after intervention compared with previous studies. Pediatricians who
      seek answers at the point of care therefore should begin to shift their
      information-seeking behaviors toward computer resources, as they are as effective
      but more time-efficient.

PMID- 14702451
TI  - An evaluation of two procedures for training skills to prevent gun play in
      children.
AB  - OBJECTIVE: Unintentional firearm injuries threaten the safety of children in the
      United States. Despite the occurrence of these injuries, few studies have
      evaluated the effectiveness of child-based programs designed to teach children
      gun-safety skills. This study compared 2 programs that were designed to reduce
      gun play in preschool children. METHODS: A between-groups no-treatment control
      design was used. Children were randomly assigned to either 1 of 2 firearm-injury
      prevention programs or a no-treatment control condition. Participant recruitment,
      training, and data collection occurred in preschools and children's homes located
      in a midwestern city with a population of approximately 80,000. Thirty-one 4- and
      5-year-old children participated in the study. The effectiveness of the National
      Rifle Association's Eddie Eagle GunSafe Program and a behavioral skills training
      program using instruction, modeling, rehearsal, and feedback was evaluated.
      Children were issued 0 to 3 ratings on the basis of their ability to say
      correctly the safety message and similar ratings on the basis of observations of
      their ability to perform correctly the skills in the classroom and when placed in
      a realistic simulation. RESULTS: Both programs were effective for teaching
      children to reproduce verbally the gun-safety message. The behavioral skills
      training program but not the Eddie Eagle GunSafe Program was effective for
      teaching children to perform gun-safety skills during a supervised role play, but
      the skills were not used when the children were assessed via real-life (in situ)
      assessments. CONCLUSIONS: Existing programs are insufficient for teaching gun
      safety skills to children. Programs that use active learning strategies
      (modeling, rehearsal, and feedback) are more effective for teaching gun-safety
      skills as assessed by supervised role plays but still failed to teach the
      children to use the skills outside the context of the training session. More
      research is needed to determine the most effective way to promote the use of the
      skills outside the training session.

PMID- 14702452
TI  - Pediatrician self-efficacy for counseling parents of asthmatic children to quit
      smoking.
AB  - BACKGROUND: Although environmental tobacco smoke is a common trigger for asthma
      exacerbations in children, pediatricians infrequently counsel parents who smoke
      to quit. High physician self-efficacy, or self-confidence, in the ability to
      counsel parents about smoking cessation is associated with increased physician
      screening and counseling on this topic. However, it is not clear which factors
      are associated with high physician self-efficacy for counseling, such as previous
      training in smoking-cessation counseling or number of years in pediatric
      practice. OBJECTIVE: To identify factors associated with high levels of physician
      self-efficacy for 4 skills associated with smoking-cessation counseling. DESIGN:
      Cross-sectional survey. PARTICIPANTS: A national random sample of 829 primary
      care pediatricians. RESULTS: The response rate was 55% (457 of 829). The
      percentage of physicians with high levels of self-efficacy for screening parents
      and screening patients to identify smokers was 87% and 84%, respectively. The
      percentage of physicians with high levels of self-efficacy for counseling parents
      and patients was 59% for both groups. The presence of previous training in
      smoking-cessation counseling was associated with high levels of self-efficacy for
      all 4 skills including inquiring about an asthma patient's smoking status (odds
      ratio [OR]: 3.91; 95% confidence interval [CI]: 1.63, 9.37); inquiring about a
      parent's smoking status (OR: 2.51; 95% CI: 1.09, 5.75); counseling a patient to
      quit smoking (OR: 5.30; 95% CI: 3.02, 9.31); and counseling a parent to quit (OR:
      4.96; 95% CI: 2.85, 8.61). Years since completion of residency were not
      associated with high self-efficacy. CONCLUSIONS: These findings suggest that
      formal training in smoking cessation has a significant impact on physician self
      efficacy related to smoking cessation throughout a physician's career.

PMID- 14702453
TI  - Girls at five are intrinsically more insulin resistant than boys: The Programming
      Hypotheses Revisited--The EarlyBird Study (EarlyBird 6).
AB  - OBJECTIVE: Recent studies of type 2 diabetes in young populations consistently
      show a predominance of affected girls over boys. Girls are more insulin resistant
      than boys. We aimed in the present report to establish how much of the sex
      difference in insulin resistance is intrinsic. METHODS: EarlyBird is a community
      based, nonintervention cohort study of 307 healthy children from school entry at
      age 5 years. It asks the question: which children are insulin resistant and why?
      Anthropometric measures, physical activity, resting energy expenditure, and
      insulin resistance and its metabolic correlates were measured. RESULTS: At 5
      years, insulin resistance was 35% higher in girls than in boys. Girls carried 26%
      more subcutaneous fat despite similar body weights. However, after correcting for
      anthropometric variables and physical activity, girls remained 33% more insulin
      resistant than boys. Triglycerides were significantly higher in girls, and high
      density lipoprotein cholesterol and sex hormone-binding globulin were
      significantly lower. CONCLUSIONS: Sex-linked genes may account for the intrinsic
      sex difference observed. These genes may have an important impact on the
      development of insulin resistance and the metabolic syndrome and may help to
      explain the female preponderance of type 2 diabetes in children. Their
      identification may also help in understanding the pathogenesis of insulin
      resistance.

PMID- 14702454
TI  - Ethical assessment of clinical asthma trials including children subjects.
AB  - BACKGROUND: The inclusion of children with asthma in clinical asthma trials is
      increasing, including their participation in placebo-controlled trials (PCTs).
      The objectives of this study are to assess whether children with asthma have been
      harmed by their participation in PCTs. METHODS: Seventy clinical asthma trials
      involving children published between January 1998 and December 2001 that involved
      distinct US research populations were identified. Studies were reviewed to
      determine whether all subjects with more than mild asthma received daily
      antiinflammatory medication as recommended by national guidelines. Sixty-two
      clinical asthma trials included data about subject withdrawal and were analyzed
      for the frequency of asthma exacerbations. RESULTS: Forty-five studies were
      designed as PCTs and did not require that all subjects with more than mild asthma
      receive antiinflammatory medications. Of 24,953 subjects, 4653 (19%) for whom
      data are available withdrew from research, and 1247 subjects (9.4%) withdrew from
      PCTs due to asthma exacerbations compared with 358 subjects (3.1%) in other
      trials. In PCTs, subjects withdrew more frequently from the placebo arms than the
      active-treatment arms and did so more frequently because of an asthma
      exacerbation (667 or 15% vs 580 or 6.5%). Fifty-two studies enrolled both
      children and adults, although only 1 performed subset analysis of the children.
      CONCLUSIONS: Subjects enrolled in PCTs of asthma have been exposed to unnecessary
      risks and harms. Clinical asthma trials involving children and adults do not
      benefit children as a class because they rarely provide subset analysis of
      children subjects.

PMID- 14702455
TI  - Neonatal cerebral infarction and neuromotor outcome at school age.
AB  - OBJECTIVE: The aim of this study was to assess neuromotor function at school age
      in children who had cerebral infarction on neonatal magnetic resonance imaging
      (MRI). DESIGN: Twenty-two children with evidence of cerebral infarction on
      neonatal brain MRI (18 with arterial infarction and 4 with border-zone lesions)
      were assessed at school age with a structured neurologic examination and the
      Movement Assessment Battery for Children, a battery of tests designed to assess
      motor function. RESULTS: Of the 22 children, 6 (30%) had hemiplegia and a further
      7 (30%) showed some neuromotor abnormality such as asymmetry on the neurologic
      examination (n = 4) or poor scores on the neuromotor test without any sign of
      asymmetry (n = 3). The remaining 9 children had a normal motor outcome.
      Hemiplegia was found only in children who had concomitant involvement of
      hemisphere, internal capsule, and basal ganglia on brain MRI. Children with
      involvement of the internal capsule, associated either with basal ganglia or
      hemispheric lesions, did not show hemiplegia but still had motor difficulties.
      CONCLUSIONS: Our results suggest that although hemiplegia occurs in a relatively
      small proportion of children with neonatal cerebral infarction, other signs of
      neuromotor impairment can be present, and these become more obvious at school age
      when a more specific assessment can be performed. These results also suggest that
      the involvement of the internal capsule on neonatal MRI can predict the presence
      of these abnormalities.

PMID- 14702456
TI  - Health status and health services utilization among US Chinese, Asian Indian,
      Filipino, and other Asian/Pacific Islander Children.
AB  - OBJECTIVE: This study examines the health status and health services access and
      utilization characteristics of US Chinese, Asian Indian, Filipino, other
      Asian/Pacific Islander (API), and non-Hispanic white children by using nationally
      representative data. METHODS: We analyzed the aggregated data file from the
      National Health Interview Survey from 1997 to 2000 including 334 Chinese, 287
      Asian Indian, 292 Filipino, 696 "other API," and 29,016 non-Hispanic white
      children <18 years old. Bivariate and multivariate analyses were conducted to
      examine the relationship between Asian ethnicities and dependent variables
      including components of health status, health services access, and utilization.
      RESULTS: Logistic regression reveals that all Asian American children were less
      likely to miss school because of illness or injury or have learning disabilities
      compared with non-Hispanic whites. Other APIs were less likely to be taking
      prescription medication for at least 3 months, and Asian Indian children were
      half as likely to have chronic conditions. Chinese, Filipino, and other API
      children were more likely to be without contact with a health professional within
      the past 12 months. Citizenship/nativity status, maternal education attainment,
      and poverty status were all significant independent risk factors for health care
      access and utilization. CONCLUSIONS: Asian ethnicities and being foreign-born are
      generally associated with more favorable health status measures such as school
      absence, learning disability, use of prescription medications, and chronic
      conditions. However, these attributes are negatively associated with health care
      access and utilization, suggesting the need for outreach to Asian immigrant
      populations to educate them on accessing the US health care system.

PMID- 14702457
TI  - Use of the Cygnus GlucoWatch biographer at a diabetes camp.
AB  - BACKGROUND: Detection and prevention of nocturnal hypoglycemia is a major medical
      concern at diabetes camps. OBJECTIVE: We conducted an open-label trial of the
      Cygnus GlucoWatch biographer to detect nocturnal hypoglycemia in a diabetes camp,
      a nonclinical environment with multiple activities. METHODS: Forty-five campers
      (7-17 years old) wore a biographer. The biographer was placed on the arm at 6:00
      PM, with the low alarm set to 85 mg/dL (4.7 mmol/L). Overnight glucose monitoring
      occurred per usual camp protocol. Counselors were to check and record blood
      glucose values if the biographer alarmed. RESULTS: Biographers were worn for 154
      nights by 45 campers. After a 3-hour warm-up period, 67% of biographers were
      calibrated, of which 28% were worn the entire night (12 hours). Thirty-four
      percent of readings were skipped because of: "data errors" (65%), sweat (20%),
      and temperature change (16%). Reported biographer values correlated with meter
      glucose values measured 11 to 20 minutes later (r = 0.90). Of 20 low-glucose
      alarms with corresponding meter values measured within 20 minutes, there were 10
      true-positive alarms, 10 false-positive alarms, and no false-negative alarms.
      Campers reported sleep disruption 32% of the nights, and 74% found the biographer
      helpful. Campers reported they would wear the biographer 4 to 5 nights each week.
      CONCLUSIONS: Half of the biographer low-glucose alarms that had corresponding
      blood meter values were true-positive alarms, and the remaining were false
      positive alarms. There was close correlation between the biographer and meter
      glucose values. The majority of campers found the biographer helpful and would
      use it at home.

PMID- 14702458
TI  - Effects of fast-food consumption on energy intake and diet quality among children
      in a national household survey.
AB  - BACKGROUND: Fast food has become a prominent feature of the diet of children in
      the United States and, increasingly, throughout the world. However, few studies
      have examined the effects of fast-food consumption on any nutrition or health
      related outcome. The aim of this study was to test the hypothesis that fast-food
      consumption adversely affects dietary factors linked to obesity risk. METHODS:
      This study included 6212 children and adolescents 4 to 19 years old in the United
      States participating in the nationally representative Continuing Survey of Food
      Intake by Individuals conducted from 1994 to 1996 and the Supplemental Children's
      Survey conducted in 1998. We examined the associations between fast-food
      consumption and measures of dietary quality using between-subject comparisons
      involving the whole cohort and within-subject comparisons involving 2080
      individuals who ate fast food on one but not both survey days. RESULTS: On a
      typical day, 30.3% of the total sample reported consuming fast food. Fast-food
      consumption was highly prevalent in both genders, all racial/ethnic groups, and
      all regions of the country. Controlling for socioeconomic and demographic
      variables, increased fast-food consumption was independently associated with male
      gender, older age, higher household incomes, non-Hispanic black race/ethnicity,
      and residing in the South. Children who ate fast food, compared with those who
      did not, consumed more total energy (187 kcal; 95% confidence interval [CI]: 109
      265), more energy per gram of food (0.29 kcal/g; 95% CI: 0.25-0.33), more total
      fat (9 g; 95% CI: 5.0-13.0), more total carbohydrate (24 g; 95% CI: 12.6-35.4),
      more added sugars (26 g; 95% CI: 18.2-34.6), more sugar-sweetened beverages (228
      g; 95% CI: 184-272), less fiber (-1.1 g; 95% CI: -1.8 to -0.4), less milk (-65 g;
      95% CI: -95 to -30), and fewer fruits and nonstarchy vegetables (-45 g; 95% CI: 
      58.6 to -31.4). Very similar results were observed by using within-subject
      analyses in which subjects served as their own controls: that is, children ate
      more total energy and had poorer diet quality on days with, compared with
      without, fast food. CONCLUSION: Consumption of fast food among children in the
      United States seems to have an adverse effect on dietary quality in ways that
      plausibly could increase risk for obesity.

PMID- 14702459
TI  - A method for interdicting the development of severe jaundice in newborns by
      inhibiting the production of bilirubin.

PMID- 14702460
TI  - Telemedicine and the future of healthcare for our children.

PMID- 14702461
TI  - The diagnosis of appendicitis: an evolving paradigm.

PMID- 14702462
TI  - Fast food and obesity in children.

PMID- 14702463
TI  - Recommendations for management of the child born through meconium-stained
      amniotic fluid.

PMID- 14702464
TI  - Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in
      children with severe sepsis.

PMID- 14702465
TI  - A method for interdicting the development of severe jaundice in newborns by
      inhibiting the production of bilirubin.

PMID- 14702466
TI  - A novel developmental and immunodeficiency syndrome associated with intrauterine
      growth retardation and a lack of natural killer cells.
AB  - OBJECTIVE: To describe a novel syndrome characterized by severe prenatal and
      postnatal growth failure, mild skeletal and facial abnormalities, and primary
      immunodeficiency. DESIGN: The syndrome was observed in 2 sisters. The elder child
      died of cytomegalovirus infection when she was 18 months old, whereas the younger
      sister is doing well at 5 years old. We report here clinical, hematologic, and
      immunologic data for both sisters and compare them with all known inherited
      disorders with similar clinical or immunologic features. RESULTS: The immune
      defect consists of a lack of detectable natural killer cells and small numbers of
      CD8 alphabeta T cells and polymorphonuclear neutrophils. This is the first report
      of prenatal and postnatal growth failure associated with mild skeletal and facial
      abnormalities and primary immunodeficiency. CONCLUSION: This novel syndrome
      probably is caused by an autosomal recessive gene defect impairing both
      intrauterine growth and natural killer cell development. The identification of
      other kindreds with this syndrome would facilitate the search for its genetic
      basis.

PMID- 14702467
TI  - Recommended childhood and adolescent immunization schedule--United States,
      January-June 2004.

PMID- 14702468
TI  - Ethical considerations in research with socially identifiable populations.
AB  - Community-based research raises ethical issues not normally encountered in
      research conducted in academic settings. In particular, conventional risk
      benefits assessments frequently fail to recognize harms that can occur in
      socially identifiable populations as a result of research participation.
      Furthermore, many such communities require more stringent measures of beneficence
      that must be applied directly to the participating communities. In this
      statement, the American Academy of Pediatrics sets forth recommendations for
      minimizing harms that may result from community-based research by emphasizing
      community involvement in the research process.

PMID- 14702469
TI  - Soft drinks in schools.
AB  - This statement is intended to inform pediatricians and other health care
      professionals, parents, superintendents, and school board members about
      nutritional concerns regarding soft drink consumption in schools. Potential
      health problems associated with high intake of sweetened drinks are 1) overweight
      or obesity attributable to additional calories in the diet; 2) displacement of
      milk consumption, resulting in calcium deficiency with an attendant risk of
      osteoporosis and fractures; and 3) dental caries and potential enamel erosion.
      Contracts with school districts for exclusive soft drink rights encourage
      consumption directly and indirectly. School officials and parents need to become
      well informed about the health implications of vended drinks in school before
      making a decision about student access to them. A clearly defined, district-wide
      policy that restricts the sale of soft drinks will safeguard against health
      problems as a result of overconsumption.

PMID- 14702470
TI  - Response to cardiac arrest and selected life-threatening medical emergencies: the
      medical emergency response plan for schools. A statement for healthcare
      providers, policymakers, school administrators, and community leaders.

PMID- 14702471
TI  - O2 saturation and slings.

PMID- 14702472
TI  - Gelatin allergy.

PMID- 14702473
TI  - Is obesity associated with early sexual maturation?

PMID- 14702474
TI  - Traumatic lumbar punctures.

PMID- 14702475
TI  - Scald burns in the bathroom: accidental or inflicted?

PMID- 14702476
TI  - Snoring.

PMID- 14702477
TI  - Usefulness or uselessness of GlucoWatch in monitoring hypoglycemia in children
      and adolescents.

PMID- 14702478
TI  - Zinc pennies in the esophagus.

PMID- 14702479
TI  - Timing of sexual maturation.

PMID- 14702480
TI  - Tubes and ear infections.

PMID- 14702481
TI  - Pediatrician patterns of prescribing vitamin supplementation for infants: do they
      contribute to rickets?

PMID- 14702482
TI  - Toilet training.

PMID- 14702483
TI  - Child abuse or parent abuse?

PMID- 14702484
TI  - Intubation and suction for meconium-stained amniotic fluid according to the
      neonatal resuscitation program: a tricky issue.

PMID- 14702485
TI  - Academic physicians just don't get it!

PMID- 14702487
TI  - Survival and long-term neurodevelopmental outcome of extremely premature infants
      born at 23-26 weeks' gestational age at a tertiary center.
AB  - OBJECTIVE: Long-term outcome, including school-age function, has been
      infrequently reported in infants born at ages as young as 23-26 weeks' gestation.
      The objective of this study is to report outcome on a large cohort of these
      infants to understand better the risks and factors that affect survival and long
      term prognosis. METHODS: Records from 1036 infants who were born between January
      1, 1986, and December 31, 2000, were analyzed retrospectively by logistic
      regression to correlate multiple factors with both survival and long-term
      outcome. A total of 675 surviving infants were analyzed at a mean age of 47.5
      months for developmental outcome. A subset of 147 surviving infants who were born
      before 1991 were followed through school-age years using the University of
      Vermont Achenbach Child Behavioral Checklist and Teachers Report Form.
      Longitudinal follow-up was performed comparing 1-year outcome with school-age
      performance. RESULTS: Gestational age and recent year of birth correlated highly
      with survival. Maternal nonwhite race, female sex, inborn status, surfactant
      therapy, single gestation, and secondary sepsis also correlated positively with
      survival. Normal cranial ultrasound results, absence of chronic lung disease,
      female sex, cesarean delivery, and increased birth weight correlated favorably
      with long-term outcome. Infants who were born at 23 weeks were more likely to
      have severe impairments compared with those who were born at 24-26 weeks. Early
      follow-up identified most subsequent physical impairments but correlated poorly
      with school-age function. CONCLUSIONS: Survival continues to improve for infants
      who are born at extremely early gestational ages, but long-term developmental
      concerns continue to be prevalent. Early outcomes do not reliably predict school
      age performance. Strategies that reduce severe intraventricular hemorrhage and
      chronic lung disease will likely yield the best chances to improve long-term
      outlook.

PMID- 14702488
TI  - Inflammatory cytokine profile in children with severe acute respiratory syndrome.
AB  - OBJECTIVE: To study the inflammatory cytokine profile in children with severe
      acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody
      to tumor necrosis factor-alpha (TNF-alpha) could be considered for treatment of
      these patients. METHODS: Plasma inflammatory cytokine concentrations (interleukin
      [IL]-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha) were monitored
      longitudinally on admission, immediately before corticosteroids, and 1 to 2 days
      and 7 to 10 days after the drug treatment in a cohort of pediatric patients (n =
      8) with virologic confirmed SARS-associated coronavirus infection. None of the
      patients required mechanical ventilation or intensive care treatment. All
      children except 1 (patient 3) received corticosteroids. RESULTS: Plasma IL-1beta
      levels (excluding patient 3) were substantially elevated immediately before
      (range: 7-721 ng/L) and 7 to 10 days after (range: 7-664 ng/L) corticosteroid
      treatment. In contrast, the plasma concentrations of other key proinflammatory
      cytokines, including IL-6 and TNF-alpha, were not overtly increased in any of the
      patients throughout the course of illness. In addition, plasma IL-10
      concentration was significantly lower 1 to 2 days and 7 to 10 days after
      corticosteroid treatment, compared with the immediate pretreatment level.
      Similarly, plasma IL-6 and IL-8 concentrations were significantly decreased 7 to
      10 days after the drug treatment. CONCLUSIONS: Pediatric SARS patients have
      markedly elevated circulating IL-1beta levels, which suggests selective
      activation of the caspase-1-dependent pathway. Other key proinflammatory
      cytokines, IL-6 and TNF-alpha, showed only mildly elevated levels at the initial
      phase of the illness. The current evidence does not support the use of TNF-alpha
      monoclonal antibody in this group of children.

PMID- 14702489
TI  - Paintball injuries in children: more than meets the eye.
AB  - OBJECTIVE: To describe the increasing incidence of ocular injuries in the
      pediatric population caused by paintballs. The awareness of this trend will help
      the physician who treats the child to give appropriate care as well as educate
      physicians, who counsel children, about this growing mechanism of pediatric
      injuries. METHODS: Previously unpublished data from the US Consumer Product
      Safety Commission were analyzed to find the frequency of ocular injuries in
      children. A review of the English-language literature was also conducted to
      describe trends with regard to age, sex, location at the time of injury, use of
      eye protection, types of injuries sustained, and long-term visual outcome.
      RESULTS: The incidence of paintball eye injuries treated in emergency departments
      has risen from an estimated 545 in 1998 to >1200 in 2000. The proportion of these
      injuries that occurred in the pediatric population may be well over 40%. These
      injuries are seen predominantly in boys, a growing proportion of whom are playing
      informally in unsupervised settings and not wearing eye protection. The cases
      previously reported include large numbers of hyphemas, retinal detachments,
      cataracts, corneal abrasions, vitreous hemorrhages, and commotio retina. Many of
      the patients in these cases sustained permanent visual impairment, with 43%
      having best vision at follow-up of 20/200 or worse. CONCLUSIONS: Pediatric eye
      injuries caused by paintballs are an unrecognized cause of severe injury and
      permanent visual loss. The advances in eye protection for participants in "war
      games" have had little if any effect on the youngest population. Children and
      teens are unlikely to wear eye protection voluntarily when playing at
      undesignated or unsupervised locations. Changes should be made to restrict
      availability of these very dangerous but easily acquired guns and ammunition.
      Practitioners must counsel young people and their caregivers to avoid injuries by
      wearing appropriate eye protection. Parents should supervise the use of paintball
      equipment as they would other activities that involve high-speed projectiles.

PMID- 14702490
TI  - Planning adenotonsillectomy in children with obstructive sleep apnea: the role of
      overnight oximetry.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) in children is usually effectively
      treated by adenotonsillectomy (T&A). However, there may be a waiting list for
      T&A, and the procedure is associated with an increased risk of postoperative
      complications in children with OSA. Needed is a simple test that will facilitate
      logical prioritization of the T&A surgical list and help to predict children who
      are at highest risk of postoperative complications. The objective of this study
      was to develop and validate a severity scoring system for overnight oximetry and
      to evaluate the score as a tool to prioritize the T&A surgical list. METHODS:
      This study comprised 3 phases. In phase 1, a severity score was developed by
      review of preoperative overnight oximetry in children who had urgent T&A in 1999
      2000. In phase 2, the score was validated retrospectively in 155 children who had
      polysomnography (PSG) before T&A in 1992-1998. In a phase 3, a 12-month
      prospective evaluation of a protocol based on the score was conducted. RESULTS:
      In phase 1, a 4-level severity score was developed on the basis of the number and
      the depth of desaturation events (normal to severely abnormal, categories 1-4).
      In phase 2, the McGill oximetry score correlated with severity of OSA by PSG
      criteria. In phase 3, a clinical management protocol was developed based on the
      score. Of 230 children tested, 179 (78%) had a normal/inconclusive oximetry
      (category 1) and went on to have PSG. Those with a positive oximetry (categories
      2-4; 22%) had no additional sleep studies before T&A. Timing of T&A was based on
      oximetry score, leading to a significant reduction in waiting time for surgery
      for those with higher oximetry scores. Postoperative respiratory complications
      were more common with increasing oximetry score. CONCLUSIONS: Overnight pulse
      oximetry can be used to estimate the severity of OSA, to shorten the diagnostic
      and treatment process for those with more severe disease, and to aid clinicians
      in prioritization of T&A and planning perioperative care.

PMID- 14702491
TI  - Identification and recall of children with chronic medical conditions for
      influenza vaccination.
AB  - OBJECTIVES: Despite long-standing recommendations to provide annual influenza
      vaccination to children with chronic medical conditions, immunization rates are
      <10% in most primary care settings. Many obstacles impede implementation of these
      recommendations, including the challenge of identifying targeted children and the
      need to immunize yearly in a short time interval. The objective of this study was
      to assess the accuracy of billing data for identifying children who have high
      risk conditions (HRCs) and need influenza vaccination and 2) to evaluate the
      efficacy of reminder/recall for children with HRCs. METHODS: The study was
      conducted in 4 private pediatric practices in metropolitan Denver, Colorado, that
      share a computerized billing system and also participate in an immunization
      registry. For all children aged 6 to 72 months, registry records were linked with
      the billing database. Patients with >or=1 encounters for an HRC in the previous
      24 months were selected, with HRCs identified from International Classification
      of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Using
      medical records as the "gold standard," we reviewed 327 randomly selected records
      to determine the sensitivity, specificity, and accuracy of billing data for
      identifying HRCs. For children with an HRC, we then conducted a randomized,
      controlled trial of reminder/recall for influenza vaccination. The primary
      outcome of the recall trial was receipt of influenza vaccine. RESULTS: Billing
      data had a sensitivity of 72% (95% confidence interval [CI]: 48%-95%),
      specificity of 95% (95% CI: 90%-100%), and overall accuracy of 90% (95% CI: 84%
      96%) in determining which children had an HRC. Of the 17,273 patients aged 6 to
      72 months, 2007 had >or=1 HRCs (12% overall; range: 9%-14% per practice).
      Asthma/reactive airways disease accounted for 87% of all HRCs. Reminder/recall
      significantly increased influenza immunization in children with HRCs, with a
      vaccination rate of 42% in those recalled, compared with 25% in control subjects.
      Recalled subjects were more likely to have an office visit (68% vs 60%) and less
      likely to have a missed opportunity to immunize (28% vs 37%) compared with
      control subjects. CONCLUSIONS: Diagnosis-based billing data accurately identified
      children who had HRCs and needed annual influenza vaccination, and registry
      driven reminder/recall significantly increased influenza immunization in targeted
      children.

PMID- 14702492
TI  - A randomized trial of calcium supplementation for childhood lead poisoning.
AB  - OBJECTIVE: Lead (Pb) poisoning remains a common disease among children despite
      successful public health efforts that have reduced its prevalence. Treatment
      options for children with blood Pb levels (BPbs) <45 micro g/dL are limited
      because chelation therapy is generally not indicated. Calcium (Ca) and Pb
      interactions are well documented. Competition for binding to Ca-binding proteins
      may underlie a mechanism for Pb absorption. The purpose of this study was to
      determine the role, if any, of supplemental Ca at reducing BPbs in moderately
      poisoned children. METHODS: Children aged 1 to 6 years with BPbs 10 to 45 micro
      g/dL were enrolled in a double-blinded, placebo-controlled trial of the effects
      of Ca supplementation on BPbs. Children received either a Ca-containing liquid or
      an indistinguishable placebo. Dosage was adjusted biweekly on the basis of
      responses to a dietary Ca intake questionnaire to reach 1800 mg in the Ca
      supplemented group. Samples for BPbs and measures to assess safety were collected
      before and after 3 months of supplementation and after an additional 3 months of
      follow-up. Bivariate and multiple regression analyses were performed. RESULTS: A
      total of 67 of 88 enrolled children with a mean age of 3.6 years completed 3
      months of supplementation. There were no statistically significant differences
      between groups on hematologic and biochemical measures, including serum and
      urinary Ca, at any time points. The average compliance rate was estimated to be
      80% for each group during the 3-month supplementation period. CONCLUSIONS: At
      enrollment, the average daily Ca intake in this group of inner-city children was
      greater than the recommended daily intake for age. Although BPbs declined during
      a 3-month period in both groups, Ca supplementation aimed at providing 1800 mg of
      Ca/day had no effect on the change in BPbs. Ca supplementation should not be
      routinely prescribed for mild to moderately Pb-poisoned children who are
      dietarily Ca sufficient.

PMID- 14702493
TI  - Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic
      solution in the treatment of children with acute otitis media with otorrhea
      through tympanostomy tubes.
AB  - OBJECTIVE: To determine the efficacy and safety of topical
      ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution
      in the treatment of acute otitis media with otorrhea through tympanostomy tubes
      (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized,
      observer-masked, parallel-group study was conducted at 39 sites in 599 children
      aged >or=6 months to 12 years with an AOMT episode of <or=3 weeks' duration. The
      mean age of patients was 2.5 years (standard deviation: 2.37 years). Patients
      received either ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension 4 drops
      twice daily for 7 days or ofloxacin 0.3% otic solution 5 drops twice daily for 10
      days. Clinical signs and symptoms of AOMT were evaluated at clinic visits on days
      1 (baseline), 3 (on therapy), 11 (end of therapy), and 18 (test of cure). A
      patient diary was used to measure time to cessation of otorrhea. Principal
      pretherapy pathogens included Streptococcus pneumoniae (16.8%), Staphylococcus
      aureus (13.0%), Pseudomonas aeruginosa (12.7%), Haemophilus influenzae (12.4%), S
      epidermidis (10.2%), and Moraxella catarrhalis (4.1%). RESULTS:
      Ciprofloxacin/dexamethasone is superior to ofloxacin for clinical cure (90% vs
      78%) and microbiologic success (92% vs 81.8%) at the test-of-cure visit, produces
      fewer treatment failures (4.4% vs 14.1%), and results in a shorter median time to
      cessation of otorrhea (4 days vs 6 days). Ciprofloxacin/dexamethasone treatment
      is also superior to improvement in clinical response by visit, absence of
      otorrhea by visit, and reduction of otorrhea volume by visit. Both topical otic
      preparations are safe and well tolerated in pediatric patients. No change in
      speech recognition threshold or decrease in hearing from baseline, based on
      audiometric testing, was noted with either regimen. CONCLUSION: Topical
      ciprofloxacin/dexamethasone treatment is superior to topical ofloxacin in the
      treatment of AOMT.

PMID- 14702494
TI  - Reimbursement for pediatric diabetes intensive case management: a model for
      chronic diseases?
AB  - OBJECTIVE: Current reimbursement policies serve as potent disincentives for
      physicians who provide evaluation and management services exclusively. Such
      policies threaten nationwide availability of care for personnel-intensive
      services such as pediatric diabetes. This report describes an approach to
      improving reimbursement for highly specialized, comprehensive pediatric diabetes
      management through prospective contracting for services. The objective of this
      study was to determine whether pediatric diabetes intensive case management
      services are cost-effective to the payer, the patient, and a pediatric diabetes
      program. METHODS: A contract with a third-party payer was created to reimburse
      for 3 key pediatric diabetes intensive case management components: specialty
      education, 24/7 telephone access to an educator (and board-certified pediatric
      endocrinologist as needed), and quarterly educator assessments of self-management
      skills. Data were collected and analyzed for 15 months after signing the
      contract. Within the first 15 months after the contract was signed, 22 hospital
      admissions for diabetic ketoacidosis (DKA) occurred in 16 different patients.
      After hospitalizations for DKA, all 16 patients were offered participation in the
      program. All were followed during the subsequent 1 to 15 months of observation.
      Ten patients elected to participate, and 6 refused participation. Frequency of
      rehospitalization, emergency department visits, and costs were compared between
      the 2 groups. RESULTS: Among the 10 participating patients, there was only 1
      subsequent DKA admission, whereas among the 6 who refused participation, 5 were
      rehospitalized for DKA on at least 1 occasion. The 10 patients who participated
      in the program had greater telephone contact with the team compared with those
      who did not (16 crisis-management calls vs 0). Costs (education, hospitalization,
      and emergency department visits) per participating patient were approximately
      1350 dollars less than those for nonparticipating patients. Differences between
      participating and nonparticipating groups included age (participants were of
      younger age), double-parent households (participants were more likely to be from
      double parent households), and number of medical visits kept (participants kept
      more follow-up visits). No differences in duration of diabetes, months followed
      in the program, sex, or ethnicity were observed. CONCLUSIONS: Contracting with
      third-party payers for pediatric diabetes intensive case management services
      reduces costs by reducing emergency department and inpatient hospital
      utilizations, likely a result of intensive education and immediate access to the
      diabetes health care team for crisis management. Such strategies may prove to be
      cost saving not only for diabetes management but also for managing other costly
      and personnel-intensive chronic diseases.

PMID- 14702495
TI  - Adenoviral infections in children: the impact of rapid diagnosis.
AB  - BACKGROUND: Adenovirus (ADV) infections were difficult to diagnose in the past,
      and many infections were unrecognized. Direct fluorescent assay (DFA) for the
      rapid diagnosis of ADV infection, as part of a viral respiratory panel, became
      available at Primary Children's Medical Center (Salt Lake City, UT) in December
      2000. OBJECTIVE: To describe children with ADV infection diagnosed by DFA and
      viral culture and document the impact of rapid ADV testing on patient care.
      METHODS: DFA testing for respiratory viruses including ADV was performed on nasal
      wash specimens with parallel viral culture. Chart review was performed for all
      ADV-positive patients identified from microbiology records between December 2000
      and May 2002. RESULTS: Of 1901 patients positive for respiratory viruses, 143
      (7.5%) were ADV-positive by DFA or culture. The mean age of ADV-positive children
      was 23 months; 90% were <or=60 months old. Eighty percent were previously
      healthy, and 56% required admission with a mean length of stay of 3.4 days. The
      most common diagnoses included fever (31%), bronchiolitis (24%), and pneumonia
      (14%). Other conditions included suspected Kawasaki disease (KD) and hepatitis.
      Forty-six percent of ADV-positive children were given antibiotics at
      presentation, but only 2 (1.4%) had documented bacterial infection (one had
      Escherichia coli urinary tract infection and one had Moraxella catarrhalis
      bacteremia). Thirty-six percent of children had a change in management based on
      positive ADV DFA. In children with suspected KD (n = 5), 100% had positive ADV
      DFA, and immune globulin was withheld in 4. One immunocompetent patient with
      fulminant liver failure received cidofovir treatment after a positive ADV DFA and
      recovered before liver transplant. CONCLUSIONS: ADV is a common infection in
      young children and often results in admission and unnecessary antibiotic therapy.
      Identifying ADV as the cause of illness can favorably impact care and in some
      instances may be life-saving. DFA testing for ADV should be considered for
      infants and children requiring admission for fever, respiratory illness,
      suspected KD, and hepatitis.

PMID- 14702496
TI  - Deep venous thrombosis in children with diabetic ketoacidosis and femoral central
      venous catheters.
AB  - OBJECTIVE: To describe findings of deep venous thrombosis (DVT) in association
      with femoral central venous catheter (CVC) placement for intensive fluid
      management in children with diabetic ketoacidosis (DKA) secondary to type 1
      diabetes. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care
      unit (PICU) of a children's referral medical center. PATIENTS: DKA patients from
      1998 to 2002 of children with DKA with and without CVC placement. DKA patients
      were also compared with all PICU patients with CVC. CVC DVT was defined as
      ipsilateral leg swelling with CVC placement, confirmed by radiographic study, and
      persisting after CVC removal. MEASUREMENTS AND MAIN RESULTS: Of 113 DKA PICU
      patients, 6 (5.3%) required femoral CVC for initial management. Three of these
      DKA/CVC patients developed ipsilateral DVT within 48 hours of CVC placement. All
      3 patients required long-term therapy with low molecular weight heparin for
      persistent leg swelling. DKA/CVC patients with DVT were younger (median age: 10.5
      months) than DKA/CVC patients without DVT. The number of DKA/CVC patients with
      DVT (1.4%) was significantly greater than for all femoral non-DKA/CVC patients.
      DKA/CVC patients were also significantly more likely to have DVT than age-matched
      shock/CVC patients. They also had significantly higher glucose, corrected sodium
      concentrations, and lower pH and serum bicarbonate than did age-matched shock/CVC
      patients. CONCLUSIONS: Femoral CVC placement is infrequently needed in pediatric
      DKA patients but can be associated with DVT. Femoral CVCs should be avoided in
      DKA patients or removed as soon as possible. DVT prophylaxis should be considered
      if a CVC is required.

PMID- 14702497
TI  - Reference values for amplitude-integrated electroencephalographic activity in
      preterm infants younger than 30 weeks' gestational age.
AB  - OBJECTIVE: To prospectively investigate the development of amplitude-integrated
      electroencephalographic (aEEG) activity during the first 2 weeks of life in
      neurologically normal and clinically stable preterm infants <30 weeks'
      gestational age (GA). PATIENTS AND METHODS: Infants with a GA of <30 weeks
      admitted to the neonatal intensive care unit of the Vienna University Children's
      Hospital (Vienna, Austria) were studied prospectively by using aEEG and cranial
      ultrasound. Clinically stable infants without clinical or sonographic evidence of
      neurologic abnormalities were eligible for inclusion in the reference group. The
      distribution of 3 background aEEG activity patterns (discontinuous low-voltage,
      discontinuous high-voltage, and continuous), presence of sleep-wake cycles, and
      number of bursts per hour in the reference group were determined by visual
      analysis. RESULTS: Seventy-five infants (median GA: 27 weeks; range: 23-29 weeks)
      were eligible for inclusion in the reference group and had aEEG recordings during
      the first 2 weeks of life available. Analysis of aEEG background activity showed
      that with higher GA the relative amount of continuous activity increased while
      discontinuous patterns decreased. The number of bursts per hour decreased with
      increasing GA. Cyclical changes in aEEG background activity resembling early
      sleep-wake cycles were observed in all infants. CONCLUSIONS: Normal values for
      aEEG background activity were determined in preterm infants <30 weeks' GA.
      Clinically stable and neurologically normal preterm infants exhibit at least 2
      different patterns of aEEG activity. There is a correlation between the GA and
      the relative duration of continuous aEEG activity.

PMID- 14702498
TI  - Genital anatomy in pregnant adolescents: "normal" does not mean "nothing
      happened".
AB  - Many clinicians expect that a history of penile-vaginal penetration will be
      associated with examination findings of penetrating trauma. A retrospective case
      review of 36 pregnant adolescent girls who presented for sexual abuse evaluations
      was performed to determine the presence or absence of genital findings that
      indicate penetrating trauma. Historical information and photograph documentation
      were reviewed. Only 2 of the 36 subjects had definitive findings of penetration.
      This study may be helpful in assisting clinicians and juries to understand that
      vaginal penetration generally does not result in observable evidence of healed
      injury to perihymenal tissues.

PMID- 14702499
TI  - Secondary prevention of vitamin D-deficiency rickets.
AB  - Reports of vitamin D-deficiency rickets and its associated morbidity continue
      among inadequately supplemented, dark-skinned breastfed infants. Despite the new
      vitamin D dietary guidelines, there remain significant numbers of unsupplemented
      breastfed infants. Here we report a case of subclinical vitamin D-deficiency
      rickets. This patient had biochemical and radiographic but not clinical evidence
      for rickets. We propose a new step of screening high-risk infants for subclinical
      rickets using wrist films paired with 25-hydroxyvitamin D levels.

PMID- 14702500
TI  - Detection of coronavirus in the central nervous system of a child with acute
      disseminated encephalomyelitis.
AB  - We present a case in which human coronavirus was detected in the cerebrospinal
      fluid of a child presumed to have acute disseminated encephalomyelitis. In murine
      models, coronavirus has been found to cause a chronic demyelinating condition
      that resembles multiple sclerosis. Additionally, there is in vitro evidence of
      human coronavirus's ability to infect neural cells. This case report provides
      additional support for the hypothesis that coronavirus may be an important
      etiologic factor in the pathogenesis of demyelinating disease in humans.

PMID- 14702501
TI  - Measuring the quality of children's health care: a prerequisite to action.
AB  - OBJECTIVE: To assess the availability and use of quality measures for children's
      health care, highlight promising developments, and develop recommendations for
      future action steps by the child health quality measurement and improvement
      fields, pediatrics, and the national quality of care enterprise generally. STUDY
      DESIGN: Two-day invitational expert meeting, informed by 3 commissioned articles.
      RESULTS: Quality of care for children is far less than optimal. A number of
      measures are available for measuring children's health care quality on a regular
      basis, although measures are scarce at least in many areas (eg, pediatric patient
      safety, end-of-life-care, mental health care, oral health care, neonatal care,
      care for school-aged children, and coordination of care). Many of the available
      measures are not being applied regularly to measure the quality of children's
      health care; barriers to implementation include lack of an information
      infrastructure that is child- and quality-friendly and lack of public support for
      improving children's health care quality. To improve the availability and use of
      quality measures for accountability and improvement, meeting participants
      recommended that at least 4 activities be national priorities: 1) build public
      support for quality measurement and improvement in children's health care; 2)
      create the information technology infrastructure that can facilitate collection
      and use of data; 3) improve the reliability, validity, and feasibility of
      existing measures; and 4) create the evidence base for measures development and
      quality improvement. CONCLUSIONS: Although substantial progress has been made in
      the development of quality measures and the implementation of quality-improvement
      strategies for children's health care, interest in quality of care for children
      lags behind that for adult conditions and disorders. Making significant progress
      will require not only sustained attention by those concerned about improving
      children's health and health care but also activities to build a broad base of
      support among the public and key health care decision-makers.

PMID- 14702502
TI  - Quality measures for children's health care.
AB  - BACKGROUND: The ability to measure and improve the quality of children's health
      care is of national importance. Despite the existence of numerous health care
      quality measures, the collective ability of measures to assess children's health
      care quality is unclear. A review of existing health care quality measures for
      children is timely for both assessing the current state of quality measures for
      children and identifying areas requiring additional research and development.
      OBJECTIVES: To identify and collect current health care quality measures for
      child health and then to systematically categorize and classify measures and
      identify gaps in child health care quality measures requiring additional
      development. DESIGN/METHODS: We first identified child health care quality
      instruments with assistance from staff at the Agency for Healthcare Research and
      Quality, experts in the field, the Computerized Needs-oriented Quality
      Measurement Evaluation System, the Child and Adolescent Health Measurement
      Initiative, and a medical literature review. From these instruments, we then
      selected clinical performance measures applicable to children (aged 0-18 years).
      We categorized the individual measures into the Institute of Medicine's framework
      for the National Health Care Quality Report. The framework includes health care
      quality domains (patient safety, effectiveness, patient-centeredness, and
      timeliness) and patient-perspective domains (staying healthy, getting better,
      living with illness, and end-of-life care). We then determined the balance of the
      measures (how well they assess care for all children versus children with special
      health care needs) and their comprehensiveness (how well the measures apply to
      the developmental range of children). Finally, we analyzed the ability of the
      measures to assess equity in care. RESULTS: We identified 19 measure sets, and
      396 individual measures were used to assess children's health care quality. The
      distribution of measures in the health care quality domains was: safety, 14.4%;
      effectiveness, 59.1%; patient-centeredness, 32.1%; and timeliness, 33.3%. The
      distribution of measures in the patient-perspective domains was: staying healthy,
      24%; getting better, 40.2%; living with illness, 17.4%; end of life, 0%; and
      multidimensional, 23.5% (measures were multidimensional if they applied to >1
      domain). Most of the measures were meant for use in the general pediatric
      population (81.1%), with a significant proportion designed for children with
      special health care needs (18.9%). The majority (>or=79%) of the measures could
      be applied to children across all age groups. However, there were relatively few
      measures designed specifically for each developmental stage. Regarding the use of
      measures to study equity in health care, 6 of the measure sets have been used in
      previous studies of equity. All the survey measure sets contain items that
      identify patients at risk for poor outcomes, and 4 are available in languages
      other than English. However, only 1 survey (Consumer Assessment of Health Plans)
      has undergone studies of cross-cultural validation. Among the measure sets based
      on administrative data, 3 included infant mortality, a well-known measure of
      health disparity. CONCLUSIONS: There are several instruments designed to measure
      health care quality for children. Despite this, we found relatively few measures
      for assessing patient safety and living with illness and none for end-of-life
      care. Few measures are designed for specific age categories among children.
      Although equity is an overarching concern in health care quality, the application
      of current measures to assess disparities has been limited. These areas need
      additional research and development for a more complete assessment of health care
      quality for children.

PMID- 14702503
TI  - Risk adjustment for pediatric quality indicators.
AB  - The movement to measure medical care quality has been accelerating, spurred on by
      evidence of poor quality of care and trials of interventions to improve care.
      Appropriate measurement of quality of care is an essential aspect of improving
      the quality of care, yet some quality measures may be influenced by patients'
      attributes unrelated to quality of care. Risk adjustment is the term commonly
      applied to those methods that account for patient-related attributes, making
      measurement of health care quality as comparable as possible across providers or
      organizations seeing different mixes of patients. The measurement of quality of
      care for children poses specific challenges. In addition to these measurement
      challenges, analysts must ensure that quality comparisons among doctors, groups
      of doctors, hospitals, or health plans are not adversely affected by the
      likelihood that different types of patients seek care in different places.
      Although some techniques designed to adjust performance measures for case mix
      were developed for both adults and children, other systems are specific to
      childhood circumstances. The theoretical issues involved in risk-adjusting
      childhood outcomes measures for newborns in the neonatal intensive care unit were
      reviewed recently. Here, we go beyond the neonatal intensive care unit setting to
      consider risk adjustment for pediatric quality measures more broadly. In
      particular, we 1) review the conceptual background for risk-adjusting quality
      measures, 2) present policy issues related to adjusting pediatric quality
      measures, and 3) catalog existing risk-adjustment methodologies for pediatric
      quality measures. We conclude with an overall assessment of the status of risk
      adjustment for pediatric quality measures and recommendations for additional
      research and application.

PMID- 14702505
TI  - Recognizing post-traumatic stress disorder.

PMID- 14702504
TI  - Implementing and using quality measures for children's health care: perspectives
      on the state of the practice.
AB  - OBJECTIVE: The objective of this study was to identify issues, obstacles, and
      priorities related to implementing and using child health care quality measures
      from the perspectives of 4 groups: 1) funders of quality-measurement development
      and implementation; 2) developers of quality measures; 3) users of quality
      measures (including Medicaid and the State Children's Health Insurance Program,
      employer coalitions, and consumer groups); and 4) health plans and providers (in
      their role as both subjects and users of quality measures). METHODS: A series of
      semistructured interviews was conducted with approximately 40 opinion leaders
      drawn from these 4 groups. The interviews were conducted by telephone between
      September and December of 2001. Major topic areas covered in the interviews were
      similar across the groups. Topic areas included 1) strategic vision and/or
      objectives for funding, developing, or using quality measures for children's
      health care; 2) a brief summary of the specific quality measures funded,
      developed, or used; 3) issues and challenges facing funders and developers of
      measures; 4) major successes achieved; 5) obstacles to implementation and use of
      measures; and 6) priority needs for future funding. RESULTS: Leaders from all 4
      groups acknowledge the importance of developing a robust set of quality measures
      that can serve multiple objectives and multiple audiences. Standardization of
      measures is viewed as a critical feature related to all objectives. An assessment
      of specific quality measures funded, developed, or used by strategic objective
      shows a high correlation between the uses intended by funders and developers and
      the actual applications of the various users. The most commonly cited measures
      across all groups are the Consumer Assessment of Health Plans Survey and Health
      Plan Employer Data and Information Set, followed by the Child and Adolescent
      Health Measurement Initiative and special topic studies to support quality
      improvement applications (eg, asthma, diabetes, etc). The major issues and
      challenges cited in common among funders and developers are 1) the lack of
      trained capacity in the field to conduct needed research and development, and 2)
      the difficulty in generating sustained interest and support among funders because
      of the complexity of quality-measurement issues, competing funding priorities in
      the face of limited funds available to allocate, and the lack of clear and
      compelling evidence that quality measurement and improvement actually result in
      better outcomes for children. The 3 most common successes cited across all 4
      groups are 1) the growing consensus and collaboration among diverse stakeholder
      groups involved in measurement development and implementation; 2) the increasing
      collection and use of specific measures; and 3) early documentation of tangible
      results in terms of improved quality of care. Specific measurement tools cited as
      successes by funders and developers include the Medicaid Health Plan Employer
      Data and Information Set, Consumer Assessment of Health Plans Survey, the Child
      and Adolescent Health Measurement Initiative, and Rand QA Tools. The most
      important obstacle reported across all groups is the lack of a strong and
      compelling "business case" that clearly demonstrates the benefits of quality
      measurement relative to the costs of implementation. Strongly related to this
      barrier is the cost of implementing and using measures without a sustainable
      source of financing as well as the absence of strong public awareness and
      political support for children's health care quality measurement. Another major
      barrier cited is the lack of coordination among funders, which prevents the field
      from developing a unified approach to addressing the numerous technical,
      political, and administrative issues also cited at length by the leaders
      interviewed. The 5 top needs for future funding identified across all 4 groups
      follow directly from the major obstacles that they reported: 1) develop the
      business case for children's health care quality measurement and improvement
      based on rigorous cost-bigorous cost-benefit analysis and documentation of
      quantifiable successes; 2) develop new measures to fill the gaps in critical
      areas (including adolescent health care, behavioral health, and chronic
      conditions) that can be applied at the hospital and ambulatory care provider
      levels; 3) invest in building needed research capacity, a trained pool of users
      of quality measures, and the capacity among providers to understand and use
      quality-improvement methods and tools; 4) invest in developing an information
      infrastructure that will support the efficient collection and use of measures for
      multiple purposes, including clinical practice, quality measurement, and quality
      improvement; and 5) develop increased public awareness and support for quality
      measurement based on improved strategies for communicating with consumers,
      purchasers, providers, and policy makers. CONCLUSIONS: Several implications are
      suggested by these perspectives for the future direction of quality measurement
      in children's health care. First, to meet the funding needs identified, many
      funders must improve coordination to reduce the noise and fragmentation generated
      by numerous competing or redundant activities. Improved coordination among
      funders will help assure maximum impact and the efficient use of scarce
      resources. Second, the importance attached to standardization of measures by both
      users and developers may conflict at times with the need for innovation and
      flexibility. Child health quality leaders will need to manage this tension
      between standardization and innovation to maintain an appropriate balance between
      the benefits of both. Finally, many of the obstacles identified are not unique to
      children's health care. Child health quality leaders will need to determine to
      what extent their efforts to overcome these obstacles can be successfully
      undertaken independently as opposed to in concert with groups concerned about
      other populations and sectors in the health care system.

PMID- 14702506
TI  - Predicting late sudden death from ventricular arrhythmia in adults following
      surgical repair of tetralogy of Fallot.
AB  - Tetralogy of Fallot was the first complex congenital cardiac defect to undergo
      open repair. The life expectancy and quality of life of those surviving surgery
      is now good, although late survival is compromised by the occurrence of sudden
      death. The emergence of successful methods for both the prevention of arrhythmias
      (including valve replacements and electrophysiological ablation) and the
      treatment of arrhythmias when they occur (including implantable defibrillators),
      has meant the identification of those at risk is of even greater importance. This
      paper reviews the predictive methods currently available to the practising
      physician caring for these increasingly common patients.

PMID- 14702507
TI  - Maximizing the benefit of treatment in mild hypertension:three simple steps to
      improve diagnostic accuracy.
AB  - BACKGROUND: Most patients only have three measurements of blood pressure before
      being labelled as hypertensive. This may lead to inaccurate classification,
      unnecessary treatment and dilution in treatment benefit for the population. AIM:
      To examine the accuracy of current methods of diagnosing mild hypertension, and
      to explore ways to improving targeting of antihypertensive treatment without
      entailing lengthy observation. DESIGN: Re-analysis of published data. METHODS: We
      tested current diagnostic methods using the data for 3965 individuals who were
      followed for a year in the placebo arm of the MRC Mild Hypertension Trial. We
      calculated the proportion selected for treatment by current methods and the
      diagnostic accuracy, using average blood pressure beyond 6 months as representing
      'true' long-term blood pressure. We examined the benefit of averaging blood
      pressures, of prolonging observation modestly and of estimating within-person
      blood pressure variability. RESULTS: Prolonging observation to 3 months selects a
      smaller (by about 12%) proportion of the sample for treatment, a proportion
      similar to that defined as 'truly' hypertensive. The diagnostic accuracy of
      current methods is poor, with up to 69% discrepancy in classification. This
      discrepancy was improved by up to 18% in absolute terms by prolonging observation
      to 3 months and using average blood pressures. Identifying those individuals with
      low within-person variability allows marked improvement in the prediction of
      'true' hypertension. DISCUSSION: Although some inaccuracy in the diagnosis of
      hypertension is inevitable, observation for 3 months, averaging blood pressures
      and estimating within-person blood pressure variability can markedly improve upon
      current practice.

PMID- 14702508
TI  - Drug treatment of stable angina pectoris and mass dissemination of therapeutic
      guidelines: a randomized controlled trial.
AB  - BACKGROUND: Public agencies responsible for implementing health care policies
      often adapt and disseminate clinical practice guidelines, but the effectiveness
      of mass dissemination of guidelines is unknown. AIM: To study the effects of
      guideline dissemination on physicians' prescribing practices for the treatment of
      stable angina pectoris. DESIGN: Randomized controlled trial. METHODS: A sample of
      3293 Quebec physicians were randomly assigned to receive a one-page summary of
      clinical practice guidelines on the treatment of stable angina (in February
      1999), to receive the summary and a reminder (in February and March 1999,
      respectively), or to receive no intervention (controls). The prescribing profiles
      of participants, as well as sociodemographic characteristics of the physicians
      and their patients, were examined for June-December 1999. RESULTS: The
      intervention had no effect on prescription rates of beta-blockers, antiplatelet
      agents, or hypolipaemic drugs. Compared to 1997 data for the same physicians,
      there was an overall 10% increase in appropriate prescription rates, irrespective
      of the intervention. DISCUSSION: In-house production and dissemination of
      clinical practice guidelines may not improve physicians' practice patterns if
      there is pre-existing substantial scientific consensus on the issue.

PMID- 14702509
TI  - Sodium valproate for painful diabetic neuropathy: a randomized double-blind
      placebo-controlled study.
AB  - BACKGROUND: Various drugs are effective in the management of painful diabetic
      neuropathy, but none is completely satisfactory. We previously found sodium
      valproate to be effective and safe in a short-term study. AIM: To test the
      effectiveness and safety of sodium valproate in the management of painful
      diabetic neuropathy over 3 months. DESIGN: Randomized double-blind placebo
      controlled study. METHODS: Consecutive attending patients with type 2 diabetes
      mellitus with painful neuropathy were asked to participate in the trial: 48
      agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain
      level and one who withdrew consent. The remaining 43 were given either drug
      (group A) or placebo (group B). Each patient was assessed clinically.
      Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual
      Analogue Score and Present Pain Intensity, at the beginning of the study, after 1
      month and after 3 months. Motor and sensory nerve conduction velocities were
      measured initially and after 3 months. Liver function tests and other adverse
      drug-related effects were assessed periodically. RESULTS: Of the 43 patients,
      four dropped out: one in group A and three in group B. There was significant
      improvement in pain score in group A, compared to group B, at 3 months (p <
      0.001). Changes in electrophysiological data were not significant. The drug was
      well-tolerated by all patients, except one, who had raised serum AST and ALT
      levels after 1 month of treatment, and whose treatment was discontinued.
      DISCUSSION: Sodium valproate is well-tolerated, and provides significant
      subjective improvement in painful diabetic neuropathy.

PMID- 14702510
TI  - Validation and comparative evaluation of the osteoporosis self-assessment tool
      (OST) in a Caucasian population from Belgium.
AB  - BACKGROUND: Risk indices have been developed to identify women at risk of low
      bone mineral density (BMD) who should undergo BMD testing. AIM: To compare the
      performance of four risk indices in White ambulatory women in Belgium. DESIGN:
      Epidemiological cross-sectional study. METHODS: Records were analysed for 4035
      postmenopausal White women without Paget's disease or advanced osteoarthritis,
      seen at an out-patient osteoporosis centre between January 1996 and September
      1999. Osteoporosis risk index scores were compared to bone density T-scores. The
      ability of each risk index to identify women with low BMD (T-score < -2.0) or
      osteoporosis (T < -2.5) was evaluated. RESULTS: Using an Osteoporosis Self
      Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from
      85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of <or= 
      2.5, and specificity ranged from 34% at the total hip to 37% at the femoral neck
      and lumbar spine. The negative predictive value was high at all skeletal sites
      (89-99%), demonstrating the usefulness of the OST to identify patients who have
      normal BMD and should not receive DXA testing. All risk indices performed
      similarly, although the OST had somewhat better sensitivity and somewhat lower
      specificity than the other indices at the cut-offs evaluated. Among the 11-12% of
      women who were classified as highest risk using OST or the Osteoporosis Index of
      Risk (OSIRIS), 81-85% had low bone mass and 68-74% had osteoporosis. DISCUSSION:
      The performance of these risk indices among women in Belgium was similar to that
      reported earlier for other samples in Asian countries, the US, and the
      Netherlands. The OST and other risk indices are effective and efficient tools to
      help target high-risk women for DXA testing.

PMID- 14702511
TI  - Interactive learning in medicine: socrates in electronic clothes.
AB  - Traditional lectures have limited ability to maintain attention and to promote
      changes in behaviour. Active learning, which stimulates the audience to think and
      participate, may be more effective. We describe our experience with an
      interactive polling system in lectures to physicians and students. Audience's
      answers to questions are displayed, providing instant feedback to both lecturer
      and audience, and promoting the use of case discussions and problem-solving
      exercises. In our experience, this modality improves the quality of clinical
      learning and deserves further evaluation.

PMID- 14702512
TI  - Do medical students and physicians understand probability?

PMID- 14702513
TI  - Sweet's syndrome associated with norfloxacin in a prostate cancer patient.

PMID- 14702514
TI  - Why?

PMID- 14702515
TI  - Escaping the loop.

PMID- 14702516
TI  - Entering our 25th year.

PMID- 14702517
TI  - Pediatric precursors of adult atherosclerosis.

PMID- 14702518
TI  - Tobacco prevention and cessation in pediatric patients.

PMID- 14702519
TI  - PREP Self-Assessment example.

PMID- 14702520
TI  - Index of suspicion.

PMID- 14702521
TI  - Successful allogeneic leg transplantation in rats in conjunction with intra-bone
      marrow injection of donor bone marrow cells.
AB  - BACKGROUND: We have recently established a new method for bone marrow
      transplantation (BMT) in mice: bone marrow cells are directly injected into the
      intra-bone marrow (IBM) cavity. IBM-BMT induces persistent donor-specific
      tolerance and enhances the rapid recovery or reconstitution of the hematolymphoid
      system of donor origin without any signs of graft-versus-host disease (GVHD) or
      graft failure. Furthermore, the prior injection of fludarabine can reduce the
      irradiation dose to the sublethal level (4.5 Gy x 2). Therefore, we hypothesize
      that IBM-BMT plus fludarabine is applicable to allogeneic leg transplantation in
      rats. METHODS: Brown Norway (BN; RT1An) rats were injected intravenously with 50
      mg/kg of fludarabine phosphate, followed by sublethal fractionated irradiation
      (4.5 Gy x 2) 1 day before IBM-BMT. The hind limbs from Fischer 344 (F344; RT1Al)
      rats were transplanted on day 0, and bone marrow cells (3 x 10(7) cells/50
      microL) obtained from the donor F344 rats were injected into the bone marrow
      cavity of the left tibias of the recipient BN rats. RESULTS: The hematolymphoid
      cells in the recipient BN rats were completely reconstituted by the cells of the
      donor F344 rats. The limbs transplanted from the donor F344 rats were accepted
      for >1 year without any clinical signs of rejection (10 of 10). The lymphocytes
      of the BN rats showed tolerance to both donor-type and recipient-type major
      histocompatibility complex determinants in mixed lymphocyte reaction, but showed
      a significant response to the third-party major histocompatibility complex
      determinants. CONCLUSIONS: Using a combination of the injection of fludarabine,
      low-dose irradiation, and IBM-BMT, we have succeeded in allogeneic limb
      transplantation without using any immunosuppressants after the operation. This
      strategy would be applicable to the transplantation of other vascularized organs
      in humans.

PMID- 14702522
TI  - Composite tissue allotransplantation in chimeric hosts part II. A clinically
      relevant protocol to induce tolerance in a rat model.
AB  - BACKGROUND: We and others have shown that mixed allogeneic chimerism induces
      donor-specific tolerance to composite tissue allografts across major
      histocompatibility complex barriers without the need for immunosuppression.
      However, a delay period between bone marrow transplantation and limb
      allotransplantation is required, making such protocols impractical for clinical
      application. This study eliminates this delay period in a rat hind limb
      allotransplantation model by performing mixed allogeneic chimerism induction and
      transplantation "simultaneously." METHODS: Group 1 included controls in which
      naive Wistar Furth (WF) hosts received ACI hind limbs. Group 2 included (ACI-
      >WF) chimeras that received limbs from third-party donors (Fisher), and group 3
      included chimeras that received irradiated (1,050 cGy) ACI limbs. In group 4, WF
      hosts conditioned with 950 cGy received irradiated (1,050 cGy) ACI limbs followed
      by infusion of 100 x 10(6) ACI T-cell-depleted bone marrow cells and
      immunotherapy (tacrolimus and mycophenolate mofetil) for 28 days. Group 5 animals
      received the same treatment as group 4 animals without immunotherapy. RESULTS:
      The rats in groups 1 and 2 rejected their limbs within 10 days. Only one rat in
      group 4 survived to the end of the study. Groups 3 and 5 demonstrated long-term
      limb survival without rejection or graft-versus-host disease. High levels of
      donor chimerism (>80%) were achieved and maintained throughout the study. Mixed
      lymphocyte reaction assays in both groups revealed donor-specific
      hyporesponsiveness with vigorous third-party reactivity. CONCLUSIONS: This study
      demonstrated that infusion of donor bone marrow cells into conditioned hosts
      immediately after limb transplantation results in stable mixed chimerism, robust
      tolerance, and reliable limb allograft survival.

PMID- 14702523
TI  - Roles of tumor necrosis factor-related apoptosis-inducing ligand in corneal
      transplantation.
AB  - BACKGROUND: Allograft rejection is still a main cause of graft failure in high
      risk keratoplasty. Tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) can selectively induce apoptosis of tumor cells without significant
      toxicity and inhibit autoimmune disease. Therefore, we attempted to determine the
      roles of TRAIL in graft survival. METHODS: Thirty-two BALB/C mice were recipients
      of corneal grafts from C57BL/6 mice. The 32 eyes were equally divided into four
      groups receiving graft without incubation with viral preparations, graft immersed
      in Dulbecco's minimum essential medium containing soluble human death receptor 5
      (sDR5) before transplantation, graft carrying the recombinant adenovirus with
      TRAIL gene (Ad-TRAIL), and graft carrying the recombinant adenovirus with green
      fluorescent protein (Ad-GFP), respectively. Pathologic and immunohistochemical
      examinations were performed, and apoptotic cells were detected. RESULTS: High
      levels of TRAIL expression were detected in the Ad-TRAIL group, which lasted more
      than 2 weeks. The mean graft survival time was 17.7, 12.3, 22.0, and 17.4 days
      for control group, sDR5 group, Ad-TRAIL group, and Ad-GFP group, respectively.
      The degrees of inflammation in tissue sections taken from all groups after the
      onset of rejection were similar. There were more apoptotic cells in the graft of
      the Ad-TRAIL group than in other groups. CONCLUSION: TRAIL appears to play an
      important role in corneal-allograft rejection and may be used to prolong the
      survival of allografts.

PMID- 14702524
TI  - Alterations of the immune response with increasing recipient age are associated
      with reduced long-term organ graft function of rat kidney allografts.
AB  - BACKGROUND: Clinically, an increasing number of older recipients are listed for
      transplantation. We examined recipient age-associated alterations of the immune
      response and their effects on graft function. METHODS: Three- and 18-month-old
      Lewis (LEW) rats received kidneys from 3- and 18-month-old Fischer 344 (F344)
      rats (1.5 mg/kg/d cyclosporine A for 10 days; n=6/group) and were observed for
      180 days. In additional groups, double kidney transplantations were performed to
      determine the impact of nephron mass and recipient age on graft outcome. RESULTS:
      All young recipients but only 66% of old recipients survived the observation
      period. Increasing recipient age resulted in a significant decrease in renal
      allograft function (P<0.001), more advanced morphologic evidence of chronic
      allograft damage (P<0.001), and greater cellular infiltration (P<0.05) and major
      histocompatibility complex expression (P<0.01) within grafts. Additional in vitro
      studies examined age-related changes in the cellular immune response by enzyme
      linked immunosorbent assay, fluorescence-activated cell sorter analysis, and
      alloreactive enzyme-linked immunospot: splenocytes from old LEW rats produced
      significantly more interleukin (IL)-2 (P<0.0001), IL-4 (P<0.05), interferon (IFN)
      gamma (P<0.0001), and tumor necrosis factor-alpha (P<0.05). IFN-gamma-producing
      memory-type T cells were significantly elevated in older rats (P<0.0001).
      Moreover, they revealed significantly more alloreactive T cells directed against
      F344 (146 +/- 64.2 and 512 +/- 277/10(6) T cells; P<0.05). Double renal
      allografts from young donors into old recipients confirmed an independent effect
      of recipient age on the acceleration of chronic graft deterioration. CONCLUSIONS:
      The enhanced cellular immune responsiveness in elderly recipients was associated
      with advanced chronic graft injury. Clinically, older recipients may need a
      modified immunosuppression.

PMID- 14702525
TI  - Dynamics of medial smooth muscle changes after carotid artery transplantation in
      transgenic mice expressing green fluorescent protein.
AB  - BACKGROUND: Recent observations have demonstrated the importance of host cells in
      neointima formation after transplantation. Because little is known regarding the
      dynamics of host-derived cells in the graft media, we investigated this question
      in a mouse carotid artery transplantation model. METHODS: C57BL/6 carotid
      arteries were orthotopically transplanted into BALB/c mice ubiquitously
      expressing enhanced green fluorescent protein. Grafts were harvested at 1, 2, 4,
      and 8 weeks after transplantation for histologic examination. No
      immunosuppression was used. RESULTS: Immunostaining and semiquantitative analysis
      of cross sections showed that donor medial smooth muscle cells decreased over
      time in the graft media, whereas green fluorescent protein-positive/smooth muscle
      alpha-actin-positive cells (i.e., cells of host origin) increased over time.
      Interestingly, host cells were located only in the inner media and the neointima
      at 2 weeks and thereafter also in the outer media, indicating that the host
      derived cells entered the media from the luminal side rather than from the
      adventitia. In longitudinal sections, there were no differences in the
      accumulation of donor- and host-derived cells between the end and middle regions
      of the graft media at 8 weeks. CONCLUSIONS: After transplantation, medial cells
      were replaced by alpha-actin-expressing host cells that were probably derived
      from circulating precursor cells. Our observations differ from the traditional
      view of a major contribution of donor medial smooth muscle cells to the neointima
      formation. Thus, circulating progenitor cells may be important for graft vessel
      disease.

PMID- 14702526
TI  - Successful renal transplantation decreases aortic stiffness and increases
      vascular reactivity in dialysis patients.
AB  - BACKGROUND: Patients with end-stage renal disease on dialysis have among the
      highest cardiovascular event rates documented. Abnormal nitric oxide (NO)
      dependent endothelial reactivity and increased arterial stiffness are commonly
      described in hemodialysis (HD) patients. Measures of aortic stiffness--aortic
      pulse wave velocity (PWV) and augmentation index (AGI)--have been shown to be
      powerful predictors of survival on hemodialysis. It is not known how these
      parameters interfere with successful renal transplantation. METHODS: PWV and
      aortic AGI (difference between the first and second systolic peak on the aortic
      pressure waveform divided by the pulse wave height) were determined from contour
      analysis of arterial waveforms recorded by applanation tonometry using a
      SphygmoCor device in 41 HD patients (20 men; age, 41.8 years) and in a control
      group of 20 patients with essential hypertension (HTA) (10 men; age, 43.6 years).
      Twenty of the HD patients (10 men; age, 39.7 years) received live-related renal
      transplants (RTx) and were restudied (3 months after RTx, normal serum
      creatinine). NO-dependent and NO-independent vascular reactivity were assessed by
      changes in AGI after challenges with inhaled salbutamol (SAL) and sublingual
      nitroglycerin (NTG), respectively. RESULTS: AGI values were significantly lower
      in RTx patients compared with subjects on hemodialysis (15.9 +/- 13.9% vs. 27.9
      +/- 11.9%, P<0.05), but similar to essential HTA controls (16.5 +/- 17%). Serial
      AGI measurements showed that successful renal transplantation is associated with
      a decrease in AGI in all cases, from a mean of 25.1 +/- 7.8% while on dialysis to
      15.9 +/- 7.0% 3 months after transplantation (P<0.0001). The responsiveness to
      both endothelium-dependent stimuli (inhaled SAL) and endothelium-independent
      stimuli (sublingual NTG) was greater in transplant patients than in hemodialysis
      patients (SAL-induced decrease in AGI -82.3 +/- 65.7% vs. 45 +/- 72.3%, P<0.01;
      and NTG-induced decrease in AGI 197 +/- 108 vs. -129.0 +/- 215.5%, P<0.01). PWV
      values in dialysis patients (7.19 +/- 1.88 m/sec) were significantly higher than
      those measured in essential HTA patients (6.34 +/- 1.32 m/sec, P<0.05) with
      normal renal function (despite similar blood pressure levels). PWV after RTx was
      6.59 +/- 1.62 m/sec, significantly different from pretransplantation (dialysis)
      values (P<0.05 for comparison) but similar to the control group of essential HTA
      patients. CONCLUSIONS: Renal transplantation is associated with marked
      improvements in vascular structure and function to a profile comparable to
      essential HTA patients.

PMID- 14702527
TI  - Long-term results of pediatric renal transplantation into a dysfunctional lower
      urinary tract.
AB  - BACKGROUND: The authors reviewed their long-term experience with pediatric renal
      transplantation into a dysfunctional lower urinary tract to evaluate the results
      of contemporary lower urinary tract evaluation and management on graft survival
      and function. METHODS: Between 1990 and 1996, 21 renal transplants were performed
      in 20 children with dysfunctional lower urinary tracts and 61 transplants were
      performed in 61 patients with normal lower urinary tracts. The minimum follow-up
      was 36 months (mean, 62.0 +/- 19.6 months). The cause of lower urinary tract
      dysfunction included posterior urethral valves (n=13), prune belly syndrome
      (n=4), meningomyelocele (n=2), and urogenital sinus abnormality (n=1).
      Urodynamics were performed on all children with dysfunctional lower urinary
      tracts. Using these perioperative assessments, lower tract management strategies
      were devised, including timed voiding alone (n=6), clean intermittent
      catheterization (n=8), bladder augmentation (n=4), and supravesical urinary
      diversion (n=2). RESULTS: Overall 5-year actuarial patient and graft survival
      rates were 100% versus 95% (P=not significant [NS]) and 83% versus 69% in the
      dysfunctional and normal urinary tract groups (P=NS), respectively. Mean serum
      creatinine levels in dysfunctional and normal urinary tract patients with
      functioning grafts at 3 years were 1.3 +/- 0.5 and 1.3 +/- 0.7 mg/dL,
      respectively (P=NS). However, 35% of patients with a dysfunctional lower urinary
      tract experienced urologic complications. CONCLUSIONS: Pediatric renal
      transplantation into a dysfunctional lower urinary tract yields outcomes
      comparable to transplantation into the normal lower urinary tract. Because of the
      high urologic complication rates, careful surveillance of lower urinary tract
      function by urodynamic evaluation is essential to optimize these outcomes.

PMID- 14702528
TI  - The changing clinical presentation of recurrent primary biliary cirrhosis after
      liver transplantation.
AB  - BACKGROUND: Recurrent disease after liver transplant is a significant problem.
      Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical
      data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a
      changing clinical presentation in recent years. MATERIALS AND METHODS: The
      diagnosis of RPBC after liver transplantation was made histologically. Data were
      obtained from our prospectively maintained liver-transplant database and
      evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants
      were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one
      patient received retransplantation, and 13 were excluded). Seventeen (10.9%)
      experienced recurrence. Median posttransplantation follow-up time was 72.1
      months. Median time to recurrence was 49.6 months. Median follow-up time after
      recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3
      use (P=0.36) before diagnosis of recurrence was significant. The combination of
      cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71
      (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without
      mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%)
      patients treated with tacrolimus and prednisolone with or without mycophenolate
      mofetil experienced recurrence. Patients treated with cyclosporine had
      numerically fewer recurrences than those treated with tacrolimus (P=0.11).
      CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors
      did not aid in predicting RPBC. The clinical course of RPBC appears to be
      different than in the earlier years of liver transplantation. Immunosuppression
      may play a role. The use and type of antimetabolite drugs had no affect on
      recurrence. RPBC demonstrated a different clinical course with tacrolimus
      treatment (shorter time to recurrence) and increased incidence when compared with
      cyclosporine treatment. Controlled randomized studies are necessary to determine
      differences between tacrolimus and cyclosporine treatment, if any.

PMID- 14702529
TI  - Late renal allograft failure between 1990 and 1998 in Spain: a changing scenario.
AB  - BACKGROUND: Our aim was to study time-dependent modifications in the
      characteristics of renal transplants in Spain during the 1990s and risk factors
      associated with death-censored graft failure after the first year. METHODS: A
      total of 3,365 adult patients who underwent transplantation in 1990, 1994, and
      1998 with a functioning graft after the first year were included. RESULTS: Ten
      year patient and graft survival rates were 82% and 70%. Major modifications
      between 1990 and 1998 were increases in donor age (32 +/- 15 to 43 +/- 18 years,
      P<0.0001) and number of HLA mismatches (2.8 +/- 1.2 to 3.2 +/- 1.2, P<0.0001).
      Acute rejection decreased from 39% to 25% (P<0.0001), and the prevalence
      recipients with hepatitis C virus decreased from 29% to 10% (P<0.0001). The use
      of lipid-lowering agents during the first year increased from 6% to 41%
      (P<0.0001). Projected renal allograft half-life estimate was 15.4 (range, 14.1
      16.8) years in 1990 and 17.7 (range, 14.0-21.4) in 1998 (P=0.007). Independent
      variables associated with graft survival were as follows: recipient age, last
      panel-reactive antibodies, acute rejection, hepatitis C virus antibodies in the
      recipient, triglycerides, serum creatinine and proteinuria at 3 months, and the
      increase of serum creatinine and proteinuria between the 3rd and 12th month. The
      use of statins during the first year was associated with a decreased risk for
      graft loss. CONCLUSION: Despite worsening of surrogate parameters of renal
      quality and poorer HLA matching, graft survival improved during the 1990s in
      Spain.

PMID- 14702530
TI  - Sirolimus delays recovery of rat kidney transplants after ischemia-reperfusion
      injury.
AB  - BACKGROUND: Sirolimus (SRL) seems to impair renal recovery from ischemic injury
      in animal models and delayed graft function after clinical renal transplantation.
      This study determined the impact of SRL on renal recovery after ischemia
      reperfusion injury in a rat kidney transplant model. METHODS: Syngeneic kidneys
      were preserved in University of Wisconsin solution before transplantation into
      bilaterally nephrectomized rats. Recipients received vehicle or SRL targeting for
      whole-blood trough levels of 10 to 20 ng/mL as measured by high-performance
      liquid chromatography. Renal function was assessed by animal survival or daily
      serum creatinine. Tissue samples were collected for histologic examination.
      RESULTS: Median SRL whole-blood concentrations were 16.6 +/- 1.6 ng/mL on
      postoperative day (POD) 1 and 12.0 +/- 0.9 ng/mL on POD 3. Transplantation of
      kidneys after 39 hr of cold storage resulted in 30% survival in the SRL-treated
      group compared with 100% survival in the control group (P=0.002). Transplantation
      of kidneys after 24 hr of cold storage resulted in no survival differences, but
      there were significant differences in renal function. Daily serum creatinine
      (PODs 1-4) was higher in the SRL-treated group compared with the control group
      (P<0.05 at all time points). Grafts from SRL-treated animals showed more severe
      tubular necrosis compared with control animals. CONCLUSIONS: When given at
      therapeutic immunosuppressive doses, SRL compromises renal function after
      ischemia-reperfusion injury in a rat kidney transplant model. The
      antiproliferative effect of SRL may translate into impairment of tubular repair
      and regeneration necessary for recovery after such injury.

PMID- 14702531
TI  - Cadaveric versus living-donor livers: differences in inflammatory markers after
      transplantation.
AB  - BACKGROUND: Prolonged cold storage of organs for transplantation may lead to
      inflammatory damage upon reperfusion. The aim of this study was to investigate
      whether organs from living donors experience less damage upon reperfusion than
      those retrieved from cadaver donors, where cold ischemia times are significantly
      longer. METHODS: Biopsies were obtained from cadaveric (n=23) and living-related
      donor (LRD) (n=10) liver transplants before and 2 hours after reperfusion.
      Cryosections were stained with antibodies against neutrophils, platelets,
      activated platelets, and endothelium. RESULTS: LRD liver allografts showed
      minimal changes postreperfusion. In contrast, after reperfusion of cadaver
      allografts, neutrophil infiltration was detected in 22% and increased expression
      of von Willebrand factor (vWF), CD41, and P-selectin in 48%, 30%, and 13% of
      allografts, respectively. In cadaver allografts with deposition of activated
      platelets expressing either P-selectin or vWF, the cold ischemia time was
      significantly longer (885 +/- 123 min vs. 608 +/- 214 min, P=0.04; 776.8 +/- 171
      min vs. 559.3 +/- 216 min, P=0.01, respectively). Increases in neutrophils and
      platelets after reperfusion were not significantly associated with clinical
      events posttransplant. However, in cadaver transplants that experienced early
      acute rejection, the mean cold ischemia time was significantly longer than in
      allografts with no rejection (732 +/- 174 min vs. 480 +/- 221 min, P=0.006).
      CONCLUSIONS: This study demonstrates that in the clinical situation, cold
      ischemia causes platelet deposition and neutrophil infiltration after reperfusion
      of cadaveric liver allografts. These early inflammatory events may contribute to
      make the graft more susceptible to acute rejection.

PMID- 14702532
TI  - The Eurotransplant Study on Twin Lung Transplants (ESOTWIN): 90 paired single
      lung transplants from the same donor.
AB  - BACKGROUND: Despite its reduced benefit for a single recipient, the
      transplantation of two single-lung allografts as opposed to one bilateral lung
      transplant has the indisputable advantage of maximizing the number of patients
      that benefit from a single donor. METHODS: In the period 1997 to 1999, 90 paired
      single-lung transplants (SLTx) from 45 donors were performed in 16 lung centers
      in Eurotransplant, with a complete follow-up of 1 year. RESULTS: No significant
      differences between left- and right-lung allograft recipients were observed
      regarding age, sex, primary disease, number of human leukocyte antigen
      mismatches, cold ischemic time, and donor-to-recipient cytomegalovirus match.
      Early posttransplant outcome, as assessed by oxygenation index at 12, 24, and 48
      hr, also did not differ significantly, and there were no differences in time to
      extubation and time spent in the intensive care unit. In the first month, six
      left- and three right-lung allograft recipients died. Bronchiolitis obliterans
      syndrome developed in 5 of 39 left-lung and 10 of 42 right-lung allograft
      recipients. If the retrieval team was different from the transplanting team, a
      significantly worse 1-year posttransplant survival rate was seen in patients who
      underwent left SLTx compared with those who underwent right SLTx (62% vs. 92%,
      respectively; P=0.04). CONCLUSIONS: More fatal posttransplant complications occur
      in patients undergoing left SLTx compared with right SLTx. A less optimistic
      assessment of the left lung by the not-implanting retrieval team is warranted.

PMID- 14702533
TI  - Prolongation of skin graft survival by modulation of the alloimmune response with
      alternatively activated dendritic cells.
AB  - BACKGROUND: Activation of immature dendritic cells (DC) in the presence of the
      glucocorticoid hormone dexamethasone (DEX) results in alternatively matured DC
      that present antigen in the absence of a proper co-stimulatory context. This
      maturation process is irreversible, making these cells an attractive potential
      tool for the induction of antigen-specific T-cell tolerance in vivo. The authors
      explored the possibility of using these DC for the induction of transplantation
      tolerance in a fully allogeneic setting in mice. METHODS: Immature dendritic
      cells (D1, an immature splenic DC line derived from B6 mice) were pretreated with
      DEX for 24 hr, after which lipopolysaccharide or nothing was added to the culture
      for another 48 hr. These cells were analyzed for their in vitro and in vivo
      stimulating or tolerizing capacities. RESULTS: In line with their phenotype,
      including decreased interleukin (IL)-12 production, in vitro co-culture of
      alternatively matured D1 (B6 origin; H-2b) with completely allogeneic T cells of
      BALB/c origin led to a significant decrease in the alloreactive T-cell response.
      A single injection of 1 x 10(6) alternatively matured H-2b DC into BALB/c mice
      induced a different alloimmune response compared with mature DC. The responding T
      cells showed a lower proliferation rate and a lower interferon-gamma production,
      whereas a significantly higher proportion of the cells produced IL-10 as measured
      ex vivo by enzyme-linked immunospot assay. Furthermore, injection with
      alternatively matured DC, followed by transplantation of fully mismatched skin
      grafts (C57BL/6), led to a significantly prolonged survival compared with that of
      mature DC-pretreated mice or untreated mice. The immunomodulatory effect was
      antigen specific, as third-party reactive alloresponses were not affected.
      CONCLUSIONS: The authors' data constitute the first direct demonstration that DC
      alternatively matured in the presence of glucocorticoid hormones can be exploited
      for the specific suppression of the alloreactive Th1 response, resulting in a
      delayed skin graft rejection in a complete major histocompatibility complex
      incompatible strain combination.

PMID- 14702534
TI  - CD8-interaction mutant HLA-Cw3 molecules protect porcine cells from human natural
      killer cell-mediated antibody-dependent cellular cytotoxicity without stimulating
      cytotoxic T lymphocytes.
AB  - BACKGROUND: CD56+ human natural killer (NK) cells are the principal anti-pig
      cytotoxic effectors in vitro. Expression of certain human leukocyte antigen (HLA)
      class I molecules in porcine cells can inhibit NK cell-mediated natural
      cytotoxicity in serum-free medium, but had not been shown to inhibit antibody
      dependent cellular cytotoxicity (ADCC) by CD16+ NK cells in the presence of human
      xenoreactive immunoglobulin G. Moreover, expression of HLA molecules might
      amplify the previously weak CD8+ cytotoxic T-lymphocyte (CTL) response against
      porcine cells. METHODS: A novel porcine B-lymphoblastoid cell line (13271) was
      stably transfected with HLA-Cw*0304 gene constructs encoding wild-type (wt) Cw3
      or genetically modified Cw3 unable to interact with CD8 (Cw3-D227K). The Cw3
      transfectants were used in limiting dilution assays to estimate the CTL precursor
      frequency in CD56-depleted human peripheral blood mononuclear cells (PBMC)
      obtained from eight unrelated donors. The 13271 transfectants were also used as
      targets for clonal and polyclonal NK cells in the presence and absence of human
      serum, to measure inhibition of ADCC. RESULTS: Expression of Cw3-wt in 13271
      cells significantly increased the human CTL response compared with the empty
      vector control transfectant, whereas no significant increase resulted from
      expression of CD8-interaction mutant Cw3-D227K molecules. The Cw3-D227K mutant
      was indistinguishable from Cw3-wt in its ability to inhibit both natural
      cytotoxicity and ADCC mediated by human NK clones that have the appropriate
      CD158b inhibitory receptor. CONCLUSIONS: Transgenic expression of HLA molecules
      in pig cells will likely amplify the CD8+ CTL response against the xenograft.
      Disruption of HLA-CD8 interaction could minimize this amplification without
      compromising NK-cell inhibition.

PMID- 14702535
TI  - Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant
      recipients: local immunosuppression or islet toxicity?
AB  - The recent success of islet transplantation using the Edmonton protocol involved
      the use of sirolimus, tacrolimus, and daclizumab for immunosuppression. Islets
      were infused into the portal circulation after transhepatic access. This protocol
      provided a unique opportunity to measure sirolimus and tacrolimus levels from the
      portal vein and compare them to systemic venous levels. A total of 11 portal
      venous samples with a corresponding peripheral venous sample were obtained from
      patients undergoing a first or second islet infusion and medication levels were
      obtained on both types of specimens. The portal-to-systemic drug level ratio
      ranged from 0.95 to 2.71 for sirolimus and 1.0 to 3.12 for tacrolimus. Given the
      potential toxicity of these agents to islets, the findings in this study may have
      implications for designing the next generation of immunosuppressive protocols for
      islet transplantation.

PMID- 14702536
TI  - Donor origin of de novo hepatocellular carcinoma in hepatic allografts.
AB  - BACKGROUND: Hepatocellular carcinomas (HCC) that originate de novo in liver
      transplants without preceding HCC in the explanted organ have only rarely been
      reported. Because recent data demonstrated a mixed hepatocellular chimerism
      caused by the integration of host-derived stem cells, a study was conducted on
      the origin of tumor cells in de novo HCC. METHODS: From two cases of de novo HCC
      arising in liver transplants after hepatitis B reinfection, tumor cells and
      nonneoplastic liver cells from the patient's own liver and donor liver were
      isolated by laser microdissection and highly polymorphic short tandem DNA repeats
      (STR) were investigated. RESULTS: Isolated tumor cells revealed donor-specific
      STR genotypes that could clearly be discriminated from the genotype of the host.
      CONCLUSIONS: Hepatitis B virus-associated de novo HCC in liver transplants is of
      donor but not host origin. The new technique described here can also discriminate
      between true recurrence of the original tumor and new recipient tumors.

PMID- 14702537
TI  - Immunosuppression with FK778 and mycophenolate mofetil in a rat cardiac
      transplantation model.
AB  - FK778 blocks the dihydro-orotate dehydrogenase, necessary for pyrimidine
      synthesis, and mycophenolate mofetil (MMF) inhibits the inosine monophosphate
      dehydrogenase, a crucial enzyme for purine biosynthesis. Beneficial
      immunosuppressive effects have been suggested for the combination of both drugs.
      The Brown Norway-Lewis rat heterotopic heart transplantation model was used.
      FK778 (5 and 20 mg/kg/day), MMF (10 and 40 mg/kg/day), or a combination of both
      drugs for 10 days was used for prevention of acute graft rejection. Grafts of
      untreated animals were rejected after 6.2 +/- 0.4 days. Low-dose FK778 and low
      dose MMF administration did not result in a significantly prolonged graft
      survival (6.7 +/- 0.8 and 8.7 +/- 1.4 days; P=not significant). Grafts of rats
      treated with high-dose FK778 or high-dose MMF survived significantly longer (17.0
      +/- 2.8 and 20.7 +/- 3.8 days; P<0.01). Concomitant use of low-dose FK778 with
      low-dose MMF produced synergistic interactions (mean survival time 12.3 +/- 2.9
      days; P<0.01; combination index=0.85). High-dose drug combination (mean survival
      time 24.0 +/- 1.4 days) showed antagonistic drug interaction (combination
      index=1.55) with increased toxic side effects.

PMID- 14702538
TI  - Extracorporeal carbon dioxide removal to control arterial pH and PACO2 in a heart
      beating donor with acute lung injury.
AB  - BACKGROUND: Arteriovenous carbon dioxide (AVCO2R) removal is a technique of
      pumpless extracorporeal carbon dioxide removal. This system has been used
      successively to control pH and PaCO2 in patients with acute lung injury who could
      not be adequately ventilated. This report describes the use of this technology in
      an organ donor awaiting harvesting. METHODS: AVCO2R was implanted using a hollow
      fiber oxygenator attached to 12 F and 14 F vascular cannulas that were inserted
      into the femoral artery and vein, respectively. Oxygen was attached to the
      oxygenator to provide the sweep gas. RESULTS: The PaCO2 and arterial pH promptly
      corrected after support was initiated (from 83-42 mm Hg and 7.18-7.38,
      respectively). CONCLUSION: This case describes the successful use of pumpless
      arteriovenous extracorporeal removal of CO2 in a heart-beating donor awaiting
      organ harvest.

PMID- 14702539
TI  - Salvage therapy with voriconazole for invasive fungal infections in patients
      failing or intolerant to standard antifungal therapy.
AB  - BACKGROUND: Invasive fungal infections (IFI), particularly those caused by
      Aspergillus and other angioinvasive molds, are associated with an excessive
      mortality despite therapy. METHODS: Voriconazole was prescribed on a
      compassionate basis to patients with IFI who were intolerant to or who had
      progressed despite standard therapy. Outcome was determined by protocol-based
      criteria as established by the consensus definitions (complete response [CR],
      partial response [PR], stable disease, failure, and intolerance). RESULTS: Forty
      five patients were enrolled in a compassionate release program (29 [64%] because
      of failure of response to standard therapy), between 1998 and 2002. Of the 45
      patients enrolled, 35 (78%) had invasive Aspergillus, 3 (7%) had Fusarium, and 2
      (4%) had Scedosporium infections. Underlying illnesses were as follows: 13 (29%)
      solid-organ transplant (SOT), 11 (24%) BMT, and 7 (13%) hematologic malignancy.
      Site of infection was as follows: 26 (58%) pulmonary, 9 (20%) disseminated, 5
      (11%) central nervous system (CNS), and 3 (7%) sinus. Overall response rates were
      as follows: 9 (20%) CR, 17 (38%) PR, 15 (33%) failure, and 4 (9%) intolerant.
      Seven of the eight (88%) patients with sinus or CNS disease demonstrated
      stabilization of the IFI. The median duration of voriconazole therapy was 79 days
      with 9 (20%) patients receiving over 1 year of therapy. Nine thousand one hundred
      twenty-eight days of therapy were given with only four serious adverse events in
      two cases considered possibly or probably drug related. CONCLUSIONS: In this
      population of severely immunocompromised patients with life-threatening IFI who
      have failed or were intolerant to standard antifungal therapy, voriconazole
      demonstrated substantial efficacy and an acceptable level of toxicity.

PMID- 14702541
TI  - Ambulatory blood pressure monitoring in renal transplantation: should ABPM be
      routinely performed in renal transplant patients?
AB  - In renal transplant recipients, hypertension is common and associated with
      increased cardiovascular and allograft rejection risks. Ambulatory blood pressure
      monitoring is required for its accurate diagnosis and adequate treatment, as it
      clearly offers several advantages over office or casual blood pressure
      measurements. First, it correlates better with target-organ damage and with
      cardiovascular mortality. Second, ambulatory blood pressure monitoring can
      eliminate "white coat" hypertension. Most important is the identification of
      nocturnal hypertension, an independent cardiovascular risk factor. A circadian
      nondipping pattern is often found in renal transplant recipients, most probably
      resulting from cyclosporine A and persistent fluid overload in the early
      posttransplant phase (approximately 70% prevalence), but reflecting an underlying
      renal (parenchymal or vascular) allograft disease when persistent (approximately
      25% prevalence) beyond the first year posttransplant.

PMID- 14702542
TI  - Ambulatory blood pressure measurement in kidney transplantation: an overview.
AB  - Adequate control of hypertension is among the most important aims of medical
      management of the kidney transplant recipient, with the aim of reducing the risk
      of premature cardiovascular disease and preserving graft function.
      Antihypertensive therapy should be adjusted according to the best available
      estimates of usual resting blood pressure. If clinic measurements are used, care
      should be taken to ensure that these measurements are taken under optimal
      conditions. Home blood pressure monitoring is a useful adjunct in many patients.
      Ambulatory blood pressure monitoring gives valuable additional data; mean
      ambulatory blood pressure correlates better with markers of target organ damage
      such as left ventricular hypertrophy. However, current treatment thresholds and
      targets are based on clinic measurements. Ambulatory blood pressure monitoring is
      certainly a useful adjunct to clinic and home blood pressure measurement, but its
      role in routine clinical practice in the transplant clinic remains to be defined.

PMID- 14702543
TI  - Treatment of posttransplant hypertension: too little, too late?

PMID- 14702544
TI  - Solving a severe cutaneous graft-versus-host reaction after bone marrow
      transplantation by allogeneic skin transplantation.

PMID- 14702545
TI  - Rituximab with plasmapheresis and splenectomy in abo-incompatible liver
      transplantation.

PMID- 14702546
TI  - Sirolimus-atorvastatin drug interaction in the pancreatic islet transplant
      recipient.

PMID- 14702548
TI  - Effect of obesity on renal transplant outcomes.

PMID- 14702549
TI  - New-onset diabetes after transplantation.

PMID- 14702551
TI  - Can prescriber profiling happen to you?

PMID- 14702550
TI  - The first case of JC virus allograft nephropathy.

PMID- 14702552
TI  - Medicaid patients bear brunt of budget cuts.

PMID- 14702553
TI  - Noninfectious liver disorders: assessment and diagnosis.
AB  - Infectious hepatitis is often the initial suspect when abnormal serum liver
      function test results are discovered in primary care settings. However,
      noninfectious liver disorders may also present with altered liver function tests.
      Noninfectious liver disorders require careful assessment of patient history,
      physical findings, and serum laboratory tests to distinguish among entities that
      have varying clinical implications and treatments.

PMID- 14702554
TI  - Noninfectious liver disorders: adult autoimmune hepatitis.

PMID- 14702555
TI  - Articulating the value-added dimension of NP care.
AB  - Collecting standardized data to describe advanced nursing practice is imperative
      to define the value-added component of nurse practitioner (NP) care. This article
      describes NPs in a primary care setting who collected standardized nursing data
      using the Omaha System. Key findings include the prevalence of health teaching,
      guidance, and counseling and surveillance as frequent intervention strategies.

PMID- 14702556
TI  - Early diagnosis key to epithelial ovarian cancer detection.
AB  - Ovarian cancer is the fourth leading cause of cancer death for women and the most
      fatal of all gynecologic malignancies. Labeled "the whispering disease," ovarian
      cancer has an insidious onset with vague symptoms such as gastrointestinal upset,
      abdominal bloating and fatigue. Early diagnosis is often delayed and patients
      present with advanced disease. This article provides an overview of ovarian
      cancer, including epidemiology, classification, risk factors, screening and early
      detection.

PMID- 14702558
TI  - The scoop on credentialing.

PMID- 14702557
TI  - First new ADHD treatment in 30 years.

PMID- 14702559
TI  - Tell me a story. Knowing when and how to use nursing stories.

PMID- 14702560
TI  - Research needed for mesothelioma. Financial compensation after death is no
      panacea.

PMID- 14702561
TI  - Making the "hit list".

PMID- 14702562
TI  - 'Think nationally, act locally'. ANA-state legislative agenda address nation's
      staffing crisis.

PMID- 14702563
TI  - Edna and the bedside tables.

PMID- 14702564
TI  - The psychosocial aspects of heart failure.

PMID- 14702565
TI  - Digital photographs in the ED.

PMID- 14702566
TI  - Gaucher disease.

PMID- 14702567
TI  - Children's self-report of pain intensity.

PMID- 14702569
TI  - Changes in sleep patterns in COPD.

PMID- 14702570
TI  - When global health is local health. Infectious diseases travel easily.

PMID- 14702571
TI  - Which heparin is best. When cardiac catheterization is needed, know your
      heparins.

PMID- 14702572
TI  - It takes a team to prevent errors.

PMID- 14702573
TI  - Refuges for refugees and their caregivers.

PMID- 14702574
TI  - Going the distance.

PMID- 14702575
TI  - 'Hierarchy of controls'.

PMID- 14702577
TI  - Dietetics on a global scale.

PMID- 14702578
TI  - The Journal has a new look.

PMID- 14702579
TI  - International dietetics.

PMID- 14702580
TI  - Demographic and health-related correlates of herbal and specialty supplement use.
AB  - BACKGROUND: By broadening the definition of a dietary supplement, the 1994
      Dietary Supplements Health and Education Act opened the market to many herbals,
      botanicals, and other food ingredients that would have otherwise needed safety
      testing before being sold. Information regarding patterns and correlates of
      herbal and specialty supplement use can help nutritionists understand which
      compounds are most commonly used, who are likely to use these supplements, and
      whether the choice of herbal supplements appears motivated by specific health
      concerns. METHODS: Data are from 61,587 participants, aged 50 to 76 years, who
      completed a self-administered mailed questionnaire in 2000-2002 on current
      dietary supplement use (20 herbal/specialty supplements, multivitamins, and 17
      individual vitamins or minerals), demographic and lifestyle characteristics, and
      medical history. RESULTS: When compared with no supplement use, herbal/specialty
      supplement use was significantly higher among respondents who were older, female,
      educated, had a normal body mass index, were nonsmokers, engaged in exercise, and
      ate a diet lower in fat and higher in fruits and vegetables (all P<.001). Similar
      trends were observed when herbal/specialty supplement users were compared with
      vitamin/mineral users. For specific supplements and medical conditions, the
      strongest associations were cranberry pills and multiple bladder infections (odds
      ratio [OR], 4.66; 95% confidence interval [CI], 4.03-5.38), acidophilus pills and
      lactose intolerance (OR, 3.37; 95% CI, 2.96-3.84), and saw palmetto and enlarged
      prostate (OR, 3.33; 95% CI, 3.00-3.72). CONCLUSIONS: Odds of supplement use are
      high for certain demographic and lifestyle characteristics. Additionally, persons
      with specific medical conditions are using supplements promoted to reduce risk
      for their particular conditions.

PMID- 14702581
TI  - Knowledge of dietary restrictions and the medical consequences of noncompliance
      by patients on hemodialysis are not predictive of dietary compliance.
AB  - OBJECTIVE: To investigate whether knowledge of the diet and medical consequences
      of noncompliance influences dietary compliance among patients on hemodialysis.
      DESIGN: An interviewer-administered questionnaire assessed patients' knowledge of
      foods restricted in their diet (four separate scores for knowledge of foods
      restricted for: potassium, phosphorus, sodium, and fluid); overall knowledge of
      restricted foods (one composite knowledge score); and knowledge of medical
      complications of dietary noncompliance (one composite knowledge score). Patients'
      mean monthly serum phosphorus and potassium and weight charts provided an
      estimate of dietary compliance. SUBJECTS/SETTING: Seventy-one of the eligible 82
      patients on hemodialysis at Nottingham City Hospital, Nottingham, UK,
      participated in the study (87% response rate). STATISTICAL ANALYSES: Chi(2) tests
      determined associations between dietary compliance and knowledge scores. RESULTS:
      More than one third of patients were noncompliant with at least one dietary
      restriction. Phosphorus dietary restrictions were the most commonly abused and
      potassium the least. Patients' knowledge of the medical consequences of
      noncompliance was poorer than knowledge of renal dietary restrictions (mean
      scores 29.4%; 74.7%). There was no association between compliance with potassium
      or sodium/fluid restrictions and knowledge of these dietary restrictions.
      However, patients with better knowledge about phosphorus were less likely to be
      compliant (P=.03). Patients with better knowledge about the medical complications
      of noncompliance were less likely to be compliant for phosphorus (P=.002) and
      sodium/fluid (P=.008) restrictions. APPLICATIONS: These findings question the
      value of current dietary education techniques in motivating patients to comply
      with dietary restrictions. Instead of the more traditional approach of
      information-giving, effective educational methods that focus on motivating
      patients to comply with dietary restrictions are needed to improve compliance.

PMID- 14702582
TI  - Convincing patients of the benefits of compliance.

PMID- 14702583
TI  - Family caregivers of older adults on home enteral nutrition have multiple unmet
      task-related training needs and low overall preparedness for caregiving.
AB  - OBJECTIVES: We used stress process theory to identify family caregiving variables
      that are salient to the experience of managing older adults' home enteral
      nutrition. In this article, we describe the specific tasks family caregivers
      performed and their unique training needs in the context of caregiver
      preparedness, competence, effectiveness, and health care use. DESIGN: Hospital
      billing lists from two university-affiliated institutions in Miami, FL, were used
      to identify older adults who had enteral tubes placed over a 6-month period.
      Consent was obtained from those older adults discharged for the first time on
      home enteral nutrition and their family caregivers at the first scheduled
      outpatient visit. SUBJECTS/SETTING: In-home interviews were conducted with a
      diverse sample of 30 family caregivers (14 white, 8 Hispanic, 7 African-American,
      1 Asian) during their first 3 months (mean=1.83+/-0.69 months) of home enteral
      nutrition caregiving. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were
      used to summarize data for all variables; chi(2) analysis was conducted to
      analyze differences in categorical variables. One-way analysis of variance was
      used to analyze mean differences among caregivers grouped by ethnicity for total
      number of hours and tasks performed. Post hoc comparisons were conducted using
      the Tukey HSD test. The Spearman rho correlations were calculated to assess
      bivariate associations between quantitative variables. RESULTS: Caregivers
      reported providing from 6 to 168 hours of care weekly (mean=61.87+/-49.67 hours),
      in which they performed an average of 19.73+/-8.09 caregiving tasks daily.
      Training needs identified were greatest for technical and nutrition-related
      tasks. Preparedness for caregiving scores were low (mean=1.72, maximum=4.0) and
      positively correlated with caregiver competence (P<.001) and self-rated caregiver
      effectiveness (P=.004). Preparedness negatively correlated with health care use
      (P=.03). CONCLUSIONS: Caregivers of older adults on home enteral nutrition need
      training for multiple nutrition-related and caregiving tasks. Multidisciplinary
      interventions, involving dietitian expertise, are needed to better prepare
      caregivers to improve both caregiver effectiveness and enteral nutrition
      outcomes.

PMID- 14702584
TI  - Higher fat intake and lower fruit and vegetables intakes are associated with
      greater acculturation among Mexicans living in Washington State.
AB  - OBJECTIVE: To examine associations of diet with acculturation among Hispanic
      immigrants from Mexico to Washington state and to compare dietary patterns of
      Hispanic with non-Hispanic white residents. DESIGN: Data are part of the baseline
      assessment for a community-randomized cancer prevention trial. The Fat-Related
      Diet Habits questionnaire and the National 5-A-Day for Better Health program
      dietary assessment instruments were used to collect data on fat and fruit and
      vegetable intake, respectively. Data were also collected on demographic
      characteristics and acculturation status. SUBJECTS/SETTING: A total of 1,689
      adult Hispanic and non-Hispanic white residents of 20 communities in the Yakima
      Valley, WA, completed in-person interviews. STATISTICAL ANALYSES PERFORMED: Mixed
      model regression analyses tested associations of acculturation with diet. These
      models compared the fat and the fruit and vegetable intake of Hispanics vs non
      Hispanic white residents. Additional analyses compared the diets of highly
      acculturated Hispanics with low-acculturated Hispanics. All models included age,
      sex, income, and education and were also adjusted for the random effect of
      community. RESULTS: Dietary patterns varied by ethnicity and acculturation
      status. On average, compared with non-Hispanic white residents, Hispanics
      consumed one more serving of fruits and vegetables per day (P<.001). Dietary
      habits changed as Hispanics acculturated to the United States. Highly
      acculturated Hispanics ate fewer servings of fruits and vegetables per day
      compared with those not highly acculturated (P<.05). Highly acculturated
      Hispanics had slightly higher, but not statistically significant, scores on the
      Fat-Related Diet Habits questionnaire, which corresponds to a higher fat intake,
      compared with low-acculturated Hispanics. The early dietary changes made on
      acculturation included adding fat at the table to breads and potatoes.
      APPLICATIONS/CONCLUSIONS: Nutrition professionals should encourage their Hispanic
      clients to maintain their traditional dietary practices, such as a high intake of
      fruits and vegetables and eating bread and potatoes without added fat.

PMID- 14702585
TI  - Evaluation of nutrition education interventions for older adults: a proposed
      framework.
AB  - This study was undertaken to identify nutrition interventions that could provide
      a basis for designing effective and measurable nutrition education programs for
      older adults. The authors conducted a literature search of articles published
      from 1990-2003 using Medline and Agricola. Key words were "elderly," "older
      adults," "nutrition intervention," and "nutrition education." Of 128 references
      identified, 25 studies included intervention and/or evaluation components and
      targeted adults over age 55 years. Although interventions tended to report
      limited success in behavior change, certain features had positive outcomes. These
      included limiting educational messages to one or two; reinforcing and
      personalizing messages; providing hands-on activities, incentives, cues, and
      access to health professionals; and using appropriate theories of behavior
      change. Based on these findings, a theoretical framework that includes these
      features but is set within a social and environmental context is proposed as a
      guideline for designing nutrition interventions for older adults.

PMID- 14702586
TI  - A call for research: what works when teaching older adults to improve their
      nutrition practices?

PMID- 14702587
TI  - Successful recruitment and retention strategies for a randomized weight
      management trial for people with diabetes living in rural, medically underserved
      counties of South Carolina: the POWER study.
AB  - We evaluated the feasibility of recruiting overweight adults with diabetes,
      living in rural, medically underserved communities, to a weight management
      intervention consisting of a 12-month clinical trial of two weight management
      programs and usual care. The sampling frame consisted of adults ages 45 years and
      older with clinically diagnosed diabetes from two community health centers. The
      recruitment process included medical record review, prescreening telephone call,
      two screening visits, and a randomization visit. Over 1,400 medical records were
      reviewed; 78.6% met eligibility criteria; 60.1% were contacted for telephone
      prescreening, and 35.5% remained eligible and were interested in participating.
      Of these, 187 completed visit 1, 164 completed visit 2, and 143 were randomized.
      Forty-six people were randomized who entered the study as walk-ins at screening
      visit 1, resulting in 189 subjects. The final yield was 21.5%. Subject mean age
      was 60.4 years, mean body mass index was 36.4 kg/m(2), 80% were African-American,
      and 46.6% had less than a high school education. Retention at 12 months was
      81.5%. Successful strategies included partnering with community health centers,
      positive reinforcement and social supportiveness, monitoring progress, and free
      transportation. This work provides a useful example of an academic-community
      partnership designed to reach groups previously considered hard to reach.

PMID- 14702588
TI  - Additional self-monitoring tools in the dietary modification component of The
      Women's Health Initiative.
AB  - Self-monitoring promotes behavior changes by promoting awareness of eating habits
      and creates self-efficacy. It is an important component of the Women's Health
      Initiative dietary intervention. During the first year of intervention, 74% of
      the total sample of 19,542 dietary intervention participants self-monitored. As
      the study progressed the self-monitoring rate declined to 59% by spring 2000.
      Participants were challenged by inability to accurately estimate fat content of
      restaurant foods and the inconvenience of carrying bulky self-monitoring tools.
      In 1996, a Self-Monitoring Working Group was organized to develop additional self
      monitoring options that were responsive to participant needs. This article
      describes the original and additional self-monitoring tools and trends in tool
      use over time. Original tools were the Food Diary and Fat Scan. Additional tools
      include the Keeping Track of Goals, Quick Scan, Picture Tracker, and Eating
      Pattern Changes instruments. The additional tools were used by the majority of
      participants (5,353 of 10,260 or 52% of participants who were self-monitoring) by
      spring 2000. Developing self-monitoring tools that are responsive to participant
      needs increases the likelihood that self-monitoring can enhance dietary reporting
      adherence, especially in long-term clinical trials.

PMID- 14702589
TI  - Obesity and the Metabolic Syndrome: implications for dietetics practitioners.
AB  - The Metabolic Syndrome encompasses a set of laboratory and physical findings,
      including central adiposity, insulin resistance, hypertension, high
      triglycerides, and low HDL-cholesterol and several abnormalities in clotting and
      inflammatory markers. Using the definition provided by the Adult Treatment Panel
      III of the National Cholesterol Education Program, 24% of adult Americans have
      the Metabolic Syndrome. Central location of fat and release of fatty acids and
      cytokines from enlarged fat cells located in the intra-abdominal fat tissue
      provide the major agents that incite this syndrome. From a practical point of
      view, identifying dietary and lifestyle factors, including low levels of physical
      activity, are important in designing a diet and exercise program that can help
      individuals with the Metabolic Syndrome to reduce the associated detrimental
      health consequences.

PMID- 14702590
TI  - Effects of promotional materials on vending sales of low-fat items in teachers'
      lounges.
AB  - This study examined the impact of an environmental intervention in the form of
      promotional materials and increased availability of low-fat items on vending
      machine sales. Ten vending machines were selected and randomly assigned to one of
      three conditions: control, or one of two experimental conditions. Vending
      machines in the two intervention conditions received three additional low-fat
      selections. Low-fat items were promoted at two levels: labels (intervention I),
      and labels plus signs (intervention II). The number of individual items sold and
      the total revenue generated was recorded weekly for each machine for 4 weeks. Use
      of promotional materials resulted in a small, but not significant, increase in
      the number of low-fat items sold, although machine sales were not significantly
      impacted by the change in product selection. Results of this study, although not
      statistically significant, suggest that environmental change may be a realistic
      means of positively influencing consumer behavior.

PMID- 14702591
TI  - Using a visual plate waste study to monitor menu performance.
AB  - Two visual plate waste studies were conducted in 1-week phases over a 1-year
      period in an acute care hospital. A total of 383 trays were evaluated in the
      first phase and 467 in the second. Food items were ranked for consumption from a
      low (1) to high (6) score, with a score of 4.0 set as the benchmark denoting a
      minimum level of acceptable consumption. In the first phase two entrees, four
      starches, all of the vegetables, sliced white bread, and skim milk scored below
      the benchmark. As a result six menu items were replaced and one was modified. In
      the second phase all entrees scored at or above 4.0, as did seven vegetables, and
      a dinner roll that replaced sliced white bread. Skim milk continued to score
      below the benchmark. A visual plate waste study assists in benchmarking
      performance, planning menu changes, and assessing effectiveness.

PMID- 14702592
TI  - Providing nutrition services for infants, children, and adults with developmental
      disabilities and special health care needs.

PMID- 14702596
TI  - What do "net carb", "low carb", and "impact carb" really mean on food labels?

PMID- 14702604
TI  - Halted trial renews questions about cancer vaccines.

PMID- 14702605
TI  - AIDS infections, deaths hit record high in 2003.

PMID- 14702606
TI  - China's new AIDS policy faces great wall of skepticism.

PMID- 14702607
TI  - The refrain in Spain is that Barbacid is to blame.

PMID- 14702608
TI  - Legal battle threatens universities' use of patented technologies.

PMID- 14702610
TI  - New vaccines enter fray in fight against tuberculosis.

PMID- 14702611
TI  - List of 'prurient' research stirs fear, anger among US scientists.

PMID- 14702612
TI  - Fatal flaw in baby formula sparks reform in Israeli ministry.

PMID- 14702615
TI  - Marc Tessier-Lavigne.

PMID- 14702617
TI  - Properties of a disease-specific prion probe.

PMID- 14702618
TI  - FasL, leukocytes and vascular modeling.

PMID- 14702622
TI  - The idiotypic network in autoimmunity: antibodies that bind antibodies that bind
      antibodies.

PMID- 14702623
TI  - THC: moderation during implantation.

PMID- 14702624
TI  - HTLV-1 sweet-talks its way into cells.

PMID- 14702625
TI  - No tolerance for depletion.

PMID- 14702626
TI  - Embryonic stem cells: staying plastic on plastic.

PMID- 14702627
TI  - Notch, the new muscle booster.

PMID- 14702628
TI  - Learning to take a deep breath--with BDNF.

PMID- 14702629
TI  - Androgen receptor outwits prostate cancer drugs.

PMID- 14702631
TI  - Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T
      cells.
AB  - Infection with malaria parasites frequently induces total immune suppression,
      which makes it difficult for the host to maintain long-lasting immunity. Here we
      show that depletion of CD4(+)CD25(+) regulatory T cells (T(reg)) protects mice
      from death when infected with a lethal strain of Plasmodium yoelii, and that this
      protection is associated with an increased T-cell responsiveness against parasite
      derived antigens. These results suggest that activation of T(reg) cells
      contributes to immune suppression during malaria infection, and helps malaria
      parasites to escape from host immune responses.

PMID- 14702632
TI  - Molecular determinants of resistance to antiandrogen therapy.
AB  - Using microarray-based profiling of isogenic prostate cancer xenograft models, we
      found that a modest increase in androgen receptor mRNA was the only change
      consistently associated with the development of resistance to antiandrogen
      therapy. This increase in androgen receptor mRNA and protein was both necessary
      and sufficient to convert prostate cancer growth from a hormone-sensitive to a
      hormone-refractory stage, and was dependent on a functional ligand-binding
      domain. Androgen receptor antagonists showed agonistic activity in cells with
      increased androgen receptor levels; this antagonist-agonist conversion was
      associated with alterations in the recruitment of coactivators and corepressors
      to the promoters of androgen receptor target genes. Increased levels of androgen
      receptor confer resistance to antiandrogens by amplifying signal output from low
      levels of residual ligand, and by altering the normal response to antagonists.
      These findings provide insight toward the design of new antiandrogens.

PMID- 14702633
TI  - Suppression of breast cancer by chemical modulation of vulnerable zinc fingers in
      estrogen receptor.
AB  - Current antiestrogen therapy for breast cancer is limited by the mixed estrogenic
      and antiestrogenic activity of selective estrogen receptor modulators. Here we
      show that the function of zinc fingers in the estrogen receptor DNA-binding
      domain (DBD) is susceptible to chemical inhibition by electrophilic disulfide
      benzamide and benzisothiazolone derivatives, which selectively block binding of
      the estrogen receptor to its responsive element and subsequent transcription.
      These compounds also significantly inhibit estrogen-stimulated cell
      proliferation, markedly reduce tumor mass in nude mice bearing human MCF-7 breast
      cancer xenografts, and interfere with cell-cycle and apoptosis regulatory gene
      expression. Functional assays and computational analysis support a molecular
      mechanism whereby electrophilic agents preferentially disrupt the vulnerable C
      terminal zinc finger, thus suppressing estrogen receptor-mediated breast
      carcinoma progression. Our results provide the proof of principle for a new
      strategy to inhibit breast cancer at the level of DNA binding, rather than the
      classical antagonism of estrogen binding.

PMID- 14702634
TI  - Regulation of the innate and adaptive immune responses by Stat-3 signaling in
      tumor cells.
AB  - Although tumor progression involves processes such as tissue invasion that can
      activate inflammatory responses, the immune system largely ignores or tolerates
      disseminated cancers. The mechanisms that block initiation of immune responses
      during cancer development are poorly understood. We report here that constitutive
      activation of Stat-3, a common oncogenic signaling pathway, suppresses tumor
      expression of proinflammatory mediators. Blocking Stat-3 in tumor cells increases
      expression of proinflammatory cytokines and chemokines that activate innate
      immunity and dendritic cells, leading to tumor-specific T-cell responses. In
      addition, constitutive Stat-3 activity induces production of pleiotropic factors
      that inhibit dendritic cell functional maturation. Tumor-derived factors inhibit
      dendritic cell maturation through Stat-3 activation in progenitor cells. Thus,
      inhibition of antitumor immunity involves a cascade of Stat-3 activation
      propagating from tumor to dendritic cells. We propose that tumor Stat-3 activity
      can mediate immune evasion by blocking both the production and sensing of
      inflammatory signals by multiple components of the immune system.

PMID- 14702635
TI  - Maintenance of pluripotency in human and mouse embryonic stem cells through
      activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.
AB  - Human and mouse embryonic stem cells (HESCs and MESCs, respectively) self-renew
      indefinitely while maintaining the ability to generate all three germ-layer
      derivatives. Despite the importance of ESCs in developmental biology and their
      potential impact on tissue replacement therapy, the molecular mechanism
      underlying ESC self-renewal is poorly understood. Here we show that activation of
      the canonical Wnt pathway is sufficient to maintain self-renewal of both HESCs
      and MESCs. Although Stat-3 signaling is involved in MESC self-renewal,
      stimulation of this pathway does not support self-renewal of HESCs. Instead we
      find that Wnt pathway activation by 6-bromoindirubin-3'-oxime (BIO), a specific
      pharmacological inhibitor of glycogen synthase kinase-3 (GSK-3), maintains the
      undifferentiated phenotype in both types of ESCs and sustains expression of the
      pluripotent state-specific transcription factors Oct-3/4, Rex-1 and Nanog. Wnt
      signaling is endogenously activated in undifferentiated MESCs and is
      downregulated upon differentiation. In addition, BIO-mediated Wnt activation is
      functionally reversible, as withdrawal of the compound leads to normal
      multidifferentiation programs in both HESCs and MESCs. These results suggest that
      the use of GSK-3-specific inhibitors such as BIO may have practical applications
      in regenerative medicine.

PMID- 14702636
TI  - Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow
      vascular niche is required for thrombopoiesis.
AB  - The molecular pathways involved in the differentiation of hematopoietic
      progenitors are unknown. Here we report that chemokine-mediated interactions of
      megakaryocyte progenitors with sinusoidal bone marrow endothelial cells (BMECs)
      promote thrombopoietin (TPO)-independent platelet production. Megakaryocyte
      active cytokines, including interleukin-6 (IL-6) and IL-11, did not induce
      platelet production in thrombocytopenic, TPO-deficient (Thpo(-/-)) or TPO
      receptor-deficient (Mpl(-/-)) mice. In contrast, megakaryocyte-active chemokines,
      including stromal-derived factor-1 (SDF-1) and fibroblast growth factor-4 (FGF
      4), restored thrombopoiesis in Thpo(-/-) and Mpl(-/-) mice. FGF-4 and SDF-1
      enhanced vascular cell adhesion molecule-1 (VCAM-1)- and very late antigen-4 (VLA
      4)-mediated localization of CXCR4(+) megakaryocyte progenitors to the vascular
      niche, promoting survival, maturation and platelet release. Disruption of the
      vascular niche or interference with megakaryocyte motility inhibited
      thrombopoiesis under physiological conditions and after myelosuppression. SDF-1
      and FGF-4 diminished thrombocytopenia after myelosuppression. These data suggest
      that TPO supports progenitor cell expansion, whereas chemokine-mediated
      interaction of progenitors with the bone marrow vascular niche allows the
      progenitors to relocate to a microenvironment that is permissive and instructive
      for megakaryocyte maturation and thrombopoiesis. Progenitor-active chemokines
      offer a new strategy to restore hematopoiesis in a clinical setting.

PMID- 14702637
TI  - Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK
      dependent pathway.
AB  - Achondroplasia is the most common genetic form of human dwarfism, for which there
      is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly
      identified molecule that regulates endochondral bone growth through GC-B, a
      subtype of particulate guanylyl cyclase. Here we show that targeted
      overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of
      achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the
      cartilage. CNP prevented the shortening of achondroplastic bones by correcting
      the decreased extracellular matrix synthesis in the growth plate through
      inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1
      pathway of FGF signaling that mediates the decreased proliferation and the
      delayed differentiation of achondroplastic chondrocytes. These results
      demonstrate that activation of the CNP-GC-B system in endochondral bone formation
      constitutes a new therapeutic strategy for human achondroplasia.

PMID- 14702638
TI  - Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the
      congenitally dysmyelinated brain.
AB  - Both late-gestation and adult human forebrain contain large numbers of
      oligodendrocyte progenitor cells (OPCs). These cells may be identified by their
      A2B5(+)PSA-NCAM(-) phenotype (positive for the early oligodendrocyte marker A2B5
      and negative for the polysialylated neural cell adhesion molecule). We used dual
      color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23
      week-old fetal human forebrain, and A2B5 selection to extract these cells from
      adult white matter. When xenografted to the forebrains of newborn shiverer mice,
      fetal OPCs dispersed throughout the white matter and developed into
      oligodendrocytes and astrocytes. By 12 weeks, the host brains showed extensive
      myelin production, compaction and axonal myelination. Isolates of OPCs derived
      from adult human white matter also myelinated shiverer mouse brain, but much more
      rapidly than their fetal counterparts, achieving widespread and dense myelin
      basic protein (MBP) expression by 4 weeks after grafting. Adult OPCs generated
      oligodendrocytes more efficiently than fetal OPCs, and ensheathed more host axons
      per donor cell than fetal cells. Both fetal and adult OPC phenotypes mediated the
      extensive and robust myelination of congenitally dysmyelinated host brain,
      although their differences suggested their use for different disease targets.

PMID- 14702639
TI  - A transgenic mouse model for monitoring endoplasmic reticulum stress.
AB  - Endoplasmic reticulum (ER) stress is caused by the accumulation of unfolded
      proteins in the ER lumen, and is associated with vascular and neurodegenerative
      diseases. Although the connection between ER stress and some disease-related
      proteins has been studied using animal models of these diseases, no in vivo data
      concerning ER stress are available. Here we report a new method for monitoring ER
      stress in vivo, based on XBP-1 mRNA splicing by inositol requiring-1 (IRE-1)
      during ER stress. The stress indicator was constructed by fusing XBP-1 and venus,
      a variant of green fluorescent protein. During stress, the spliced indicator mRNA
      is translated into an XBP-1-venus fusion protein, which can be detected by its
      fluorescence. We used transgenic animals expressing the ER stress indicator to
      show that it can be used to monitor physiological and pathological ER stress in
      vivo.

PMID- 14702644
TI  - Vinculin activation by talin through helical bundle conversion.
AB  - Vinculin is a conserved component and an essential regulator of both cell-cell
      (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions)
      junctions, and it anchors these adhesion complexes to the actin cytoskeleton by
      binding to talin in integrin complexes or to alpha-actinin in cadherin junctions.
      In its resting state, vinculin is held in a closed conformation through
      interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin
      to focal adhesions requires its association with talin. Here we report the
      crystal structures of human vinculin in its inactive and talin-activated states.
      Talin binding induces marked conformational changes in Vh, creating a novel
      helical bundle structure, and this alteration actively displaces Vt from Vh.
      These results, as well as the ability of alpha-actinin to also bind to Vh and
      displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh
      functions as a domain that undergoes marked structural changes that allow
      vinculin to direct cytoskeletal assembly in focal adhesions and adherens
      junctions. Notably, talin's effects on Vh structure establish helical bundle
      conversion as a signalling mechanism by which proteins direct cellular responses.

PMID- 14702645
TI  - Long-term study on the effects of visual biofeedback and muscle training as a
      therapeutic modality in pelvic floor dyssynergia and slow-transit constipation.
AB  - PURPOSE: Biofeedback training has been shown as an effective therapeutic measure
      in patients with pelvic floor dyssynergia, at least in the short term. Long-term
      effects have received less attention. Moreover, its effects in patients with slow
      transit constipation have been scarcely investigated. This study was designed to
      assess in an objective way the medium- and long-term effects of biofeedback and
      muscle training in patients with pelvic floor dyssynergia and slow-transit
      constipation. METHODS: Twenty-four patients (14 with pelvic floor dyssynergia and
      10 with slow transit) meeting the Rome II criteria for constipation, and
      unresponsive to conventional treatments, entered the study. Clinical evaluation
      and anorectal manometry were performed basally and three months after a cycle of
      electromyographic biofeedback and muscle training; moreover, a clinical interview
      was obtained one year after biofeedback. Patients with slow-transit constipation
      also had colonic transit time reassessed at one year. RESULTS: Clinical variables
      (abdominal pain, straining, number of evacuations/week, use of laxatives) all
      significantly improved in both groups at three-month assessment; anorectal
      manometric variables remained unchanged, apart from a significant decrease of
      sensation threshold in the pelvic floor dyssynergia group and of the maximum
      rectal tolerable volume in the slow-transit constipation group. At one-year
      control, 50 percent of patients with pelvic floor dyssynergia still maintained a
      beneficial effect from biofeedback, whereas only 20 percent of those complaining
      of slow-transit constipation did so. Moreover, the latter displayed no
      improvement in colonic transit time. CONCLUSIONS: In our experience, patients
      with pelvic floor dyssynergia are likely to have continued benefit from
      biofeedback training in the time course, whereas its effects on slow-transit
      constipation seems to be maximal in the short-term course.

PMID- 14702646
TI  - Strategy for selection of type of operation for rectal prolapse based on clinical
      criteria.
AB  - PURPOSE: Reports of outcome after surgery for rectal prolapse predominantly
      relate to single operative procedures. A single surgical operation is not
      appropriate for all patients with rectal prolapse. We describe a selective policy
      based on clinical criteria. METHODS: Patients were offered surgery according to
      the following broad clinical protocol. Those who were unfit for abdominal surgery
      had a perineal operation. The remainder had a suture abdominal rectopexy. A
      sigmoid resection was added for patients in whom incontinence was not a
      predominant symptom. RESULTS: Surgery was performed in 159 patients. Of these, 57
      had a perineal operation, 65 had fixation rectopexy, and 37 had resection
      rectopexy. There were no in-hospital deaths, and major complications occurred in
      five patients (3.5 percent). Minimum follow-up was 3 years. Of the 143 patients
      with long-term follow-up, recurrence occurred in 7 (5 percent). Constipation
      increased from 41 to 43 percent (59-61/143) and incontinence decreased from 43 to
      19 percent (61 to 27/143). CONCLUSIONS: A selective policy has improved outcome
      compared with reports of a single operation. Future studies might consider an
      objective method of selecting the type of operation for rectal prolapse.

PMID- 14702647
TI  - Per-anal excision of large, rectal, villous adenomas.
AB  - PURPOSE: Considering the malignant potential of villous adenoma of the rectum,
      complete resection at the first intervention is desirable and yet many series
      suggest that a high recurrence rate must be expected. The experience of one
      colorectal surgeon in the management of this condition is described. METHODS:
      Between 1993 and 2000, 50 patients underwent per-anal resection of villous
      adenoma. The procedure was conducted in the prone jackknife position unless
      contraindicated, with dissection performed using a diathermy blade, with
      particular attention to circumferential and deep margins of excision. RESULTS:
      The mean distance of the proximal margin of the tumor from the dentate line was
      5.6 (range, 0.5-11) cm. The mean length of the tumor was 5.2 (range, 0.5-9) cm.
      Mean anesthetic time was 27 (range, 10-110) minutes, and median hospital stay was
      two (range, 1-14) days. There was no significant perioperative morbidity and no
      mortality. On histology of ten patients, there were foci of adenocarcinoma.
      Excision was complete histologically in 49 patients. The median follow-up was 30
      (range, 6-91) months. The patient with incomplete excision developed a probable
      recurrence after six months, which was ablated with diathermy (residual tumor
      rate, 2.1 percent). Two patients have subsequently developed villous adenoma at
      different sites within the rectum (metachronous tumor rate, 4.3 percent).
      CONCLUSIONS: Many series of this procedure report recurrence in up to 36 percent
      and significant complication in up to 19 percent of patients. Transanal
      endoscopic microsurgery has achieved recurrence rates of 2.8 percent and low
      complication rates but for economic reasons has failed to find a widespread role.
      This article demonstrates that large, villous tumors of the low and mid rectum
      can be simply and effectively treated by per-anal resection with recurrence rates
      equivalent to transanal endoscopic microsurgery.

PMID- 14702649
TI  - Oral exposure to PAH: bioactivation processes in the human gut.

PMID- 14702650
TI  - Inactivation of Bacillus cereus spores in milk by mild pressure and heat
      treatments.

PMID- 14702651
TI  - Bruising mechanism in tomato fruit: concerted biomechanical and enzymatic action.

PMID- 14702652
TI  - Combined discrete and continuous simulation of controlled atmosphere (CA) storage
      systems.

PMID- 14702653
TI  - Characterization of spoilage through heterofermentative lactic acid bacteria and
      Brochotrix spp. on vacuum packaged cooked ham.

PMID- 14702654
TI  - Self-organisation of zeolite nanoslabs in microgravity.

PMID- 14702655
TI  - Biotechnological developments for the assessment of radiobiological impact of
      cosmic radiation during the Belgian soyuz flight to the International Space
      Station.

PMID- 14702656
TI  - The advantages of the use of open source software in geosciences.

PMID- 14702657
TI  - Modelling the dynamic flow of water through young oak and beech trees.

PMID- 14702658
TI  - Enhancing wastewater sludge dewatering by polyelectrolyte conditioning.

PMID- 14702660
TI  - The self-caring nurse. Strategies for avoiding compassion fatigue and burnout.

PMID- 14702661
TI  - [Changes in Staphylococcus aureus susceptibility to bactericidal action of
      teicoplanin in the presence of different prophages in the bacterial genome].
AB  - The influence exerting by lysogeny state on the susceptibility of Staphylococcus
      aureus to bactericidal action of teicoplanin was studied. In this aim the
      standard, non-lysogenic, bacteriophage-free S. aureus NCTC 8325-4 strain was
      lysogenized with 10 different, bacteriophages obtained in our laboratory. All
      bacteriophages were derived from multiresistant S. aureus strains and all were
      able to convert staphylokinase. For all derivatives MBCs and MICs of teicoplanin
      were determined. In the case of four strains the ratio MBC/MIC showed the
      presence of tolerance to teicoplanin (MBC/MIC > or = 32) and was significantly
      higher than in the case of the parent strain NCTC8325-4. In the case of two
      strains this ratio was smaller than for parent strain. Only small correlation
      with our previous results obtained for vancomycin was observed.

PMID- 14702662
TI  - [Searching for Staphylococcus aureus strains with reduced susceptibility to
      glycopeptides among clinical isolates obtained during the year of 2002].
AB  - The methicillin-resistant strains of S. aureus (MRSA) isolated in our laboratory
      were searched for strains with decreased susceptibility to glycopeptides, GISA
      (glycopeptide intermediate Staphylococcus aureus) and hetero-GISA strains. 103
      strains isolated in 2002 were investigated. Five h-VISA and none VISA strain were
      found. There was not observed any increase in the frequency of VISA and h-VISA
      comparing to the former years. In the case of some clinical as well as standard
      strains (susceptible, GISA and especially h-GISA) the start inoculum
      significantly influenced a shape of the growth curve obtained as a result of the
      population analysis.

PMID- 14702663
TI  - [Characteristic of saccharose fermentation by pathogenic Escherichia coli strains
      -phenotypic and genotypic elements].
AB  - The purpose of the study was to characterize fermentation of sucrose by
      Escherichia coli strains and to answer why some of these strains doesn't utilize
      this disaccharide. Investigations included 16 E. coli strains. Only 5 of these
      strains utilized sucrose. Genotypic analysis demonstrated the presence of cscB
      gene (encoding the sucrase permease which catalyzes transport of sucrose through
      the plasma membrane of the cell) in 5 strains of E. coli and cscA gene (encoding
      an enzyme sucrase that catalyzes the utilization of sucrose) in 6 strains of E.
      coli. These 5 of E. coli strains which possessed a chromosomally encoded sucrose
      metabolic pathway utilized sucrose with a different time. 3 of them destroyed
      this disaccharide after 24 h and 2 of them destroyed it after 48 h. Ten of E.
      coli strains hadn't cscA gene and 11 of them had not cscB genes. The lack of
      these genes can be the prove that it is not possible for 11 of E. coli strains to
      synthesize sucrose permease and for 10 of them to synthesize sucrase and it may
      be the reason of not utilize disaccharide sucrose by these bacteria.

PMID- 14702664
TI  - [Selected features determine pathogenicity of Staphylococcus haemolyticus].
AB  - The study have been done on S. haemolyticus strains isolated from patients
      hospitalized an Surgical Unit. Aim of the study was to determine pathogenic
      traits of S. haemolyticus: slime producing, adhesion to biomaterials, antibiotics
      susceptibility and the profiles of surface proteins. Among 44 S. haemolyticus
      strains, in the test-tube method, there have been 38% labeled as slime producing
      and 62% as non-producing. In the plate method at 48% slime production was
      noticed, while 52% strains did not produce slime. It is quite significant that
      all CNS strains which have an ability to produce mucus, that was proved by means
      of two methods (test-tube and plate), show a high level of TTC's reduction to
      formazan. The analysis of resistance to antibiotics in relation to slime
      production demonstrated more frequent antibiotic resistance of the slime
      producing strains.

PMID- 14702665
TI  - [Polymorphism analysis of Haemophilus influenzae strains isolated from healthy
      children with respect to amplification reaction].
AB  - The random-amplified polymorphic DNA (RAPD) assay was used to generate DNA
      fingerprints for 44 isolates H. influenzae obtained from healthy children.
      Problems with reproducibility and discriminatory power, frequently cited in the
      literature, were overcome by optimization procedure allowing to achieve reliable
      conditions for H. influenzae analysed. Particular parameters of RAPD
      fingerprinting were evaluated with respect to selection of best working primer,
      DNA polymerase and DNA concentration for amplification pattern. This study proved
      high sensitivity and efficiency of optimized RAPD profiling applicable for
      searching the epidemiology traces.

PMID- 14702666
TI  - [Phenotype and genotype of Clostridium sp. strains producing botulism
      neurotoxin].
AB  - Neurotoxins produced by strains of Clostridium sp. are belonging to the most
      toxic biological substances. In the study phenotypes and genotypes of C.
      botulinum strains in animal studies in vivo and on the DNA level were evaluated,
      respectively. Additionally, the presence of genes encoding BoNT toxins of A, B,
      and E types among strains of Clostridium sp. were identified. In case of C.
      botulinum DNA was isolated from vegetative bacterial cells and from spores. Two
      different genes encoding two different neurotoxins harboured by three strains of
      Ae biotype/ae genotype, and by two strains of B biotype/be genotype were
      detected. Additionally, above E type C. botulinum strains, the presence of gene
      encoding E type neurotoxin, was found in genome of two C. baratii, two C.
      butyricum, and C. bifidobacterium, and C. oedematicum strains. C. bifidobacterium
      and C. oedematicum strains positive for presence of gene encoding E type
      neurotoxin, were found negative for E neurotoxin production in vivo in TN test.
      The study indicates that genes encoding BoNT/E neurotoxins are very common among
      Clostridium species. Phenotype and genotype analysis indicated co-presence of B
      phenotype together with be genotype and A phenotype together with ae genotype
      among C. botulinum strains.

PMID- 14702667
TI  - [Assessment of susceptibility to metronidazole and vancomycin of Clostridium
      difficile strains isolated between 1998-2002].
AB  - The drugs of choice used to treat C. diffcile associated diarrhoea (CDAD) are
      metronidazole and vancomycin. C. difficile strains isolated in most laboratories
      are susceptible to metronidazole and vancomycin. Communication about emergence of
      antimicrobial resistance among C. difficile strains in some countries to
      metronidazole and intermediate resistance to vancomycin are alarming. This study
      was performed to determine the susceptibility to metronidazole and vancomycin of
      140 C. difficile strains isolated from patients with CDAD hospitalised in
      academic hospital between 1999-2002. Resistance to metronidazole and vancomycin
      was not observed.

PMID- 14702668
TI  - [Bacterial and fungal bloodstream infections in patients at the University
      Hospital of Cracow].
AB  - In presented material evaluation of changes in sepsis and types of bloodstream
      infections of hospitalized patients in Wards of the University Hospital in Cracow
      were examined. Results of 9,138 blood cultures studied in years 1989-1999 were
      analysed. All of the blood samples were recovered from 4,656 infected adults at
      Clinics of the University Hospital in Cracow. Microbiological blood examinations
      were held in system of constant monitoring of isolated cultures applying
      BacT/Alert--colorimetric system (Organon Teknika). Cultured micro--organisms were
      identified using commercial biochemical tests (bio-Merieux). During period of
      research changes of profile of isolated microorganisms was observed. Percentage
      of blood infections of Enterococcus spp. etiology increased from 2.2% in 1989 to
      9.8% in 1997-98 (p = 0.014). Dynamic growth of non-fermentative S. maltophilia
      bacilli to 5.5% (p = 0.036) and Serratia marcescens to 13.8% (p = 0.042) in 1999
      was revealed. Designed according to our research review of fungal flora in years
      1989-1999 revealed tendency of systematic growth of invasive candidemia
      frequency, from 1.1% to 10.4%. Diagnostic and therapeutic profile of Departments
      was in a strict connection with increase of the number and meaning of the
      politiological bacteremias (p = 0.036) in total number of systemic infections
      cases.

PMID- 14702669
TI  - [Analysis of the microorganisms isolated from kidney recipients treated in the
      Department of Clinical Transplantology and General Surgery, Medical University in
      Bydgoszcz in 2001 year].
AB  - One of the most important reasons of complications after organ transplantation
      may be the infections. The aim of the present work was to analyse of
      microorganisms isolated from patients, which were the recipients for kidney
      transplantation in 2001 year. The diagnostic material contained 140 samples from
      53 patients, 40 (22.2%) samples from Euro-Collins fluid used for kidney storage
      before the transplantation and 3 end-pieces of catheter. The positive cultures
      were found in 125 (69.4%) samples. Gram-positive bacteria constituted 58.4%, Gram
      negative bacteria--34.2%, fungi--7.4%. 140 strains of microorganisms were
      isolated from pharyngeal swabs and 55 strains of bacteria were isolated from palm
      swabs. Most of them were considered as a physiological flora. It was found 4-time
      significant bacteriuria among positive cultures from urine samples. In the
      cultures of fluid used for kidney storage 12 (30.0%) positive samples were
      obtained, out of which 16 strains of microorganisms were isolated. Among the
      strains of Staphylococcus 35.3% were MR. Among 18 strains of Gram-negative rods
      one strain was multiresistant to antibiotics. None of analyzed strains was ES
      beta L-producing. A high percentage of positive cultures from fluid used for
      kidney storage suggests the possibility of contamination of the organ with
      bacteria coming from kidney donor or during the storage, transport and actions
      connected with taking the organ to the transplantation.

PMID- 14702670
TI  - [The evaluation of prevalence and the impact of pathological microflora of the
      lower genital tract among women at early pregnancy on the risk of preterm
      delivery].
AB  - The main aim of this prospective study was to determine the prevalence and an
      association between pathological microflora of the lower genital tract diagnosed
      at early pregnancy and the risk of preterm delivery. The study group comprised
      179 randomly selected pregnant women from Lodz region, between 8 and 16 week of
      pregnancy. For the qualitative and quantitative assessment of biocenosis of the
      lower genital tract vaginal and cervical swabs were collected from the pregnant
      women under study. The C. trachomatis antigen was detected by direct
      immunofluorescence assay. The vaginal swabs were tested for aerobic and anaerobic
      bacteria. Bacterial vaginosis was diagnosed by Gram stain according to Spiegel's
      criteria. To evaluate the risk factors odds ratios were calculated using EPI INFO
      software. 21 (11.7%) women delivered before 37th week of pregnancy. Bacterial
      vaginosis was diagnosed among 51 (28.5%) pregnant women while intermediate
      microflora was diagnosed by Gram stain in 62 (34.6%) women. The shortest mean
      gestational age at delivery was noted among women with BV. The rate of preterm
      delivery in BV group was 15.7% comparing to 9.1% among women with normal
      microflora. Among women with preterm delivery BV was diagnosed in 38.1% (OR =
      1.86). Based on culture results only 84 (46.9%) women had normal microflora at
      early pregnancy. The pathological culture was associated with slightly increased
      preterm delivery rate (12.6%) as compare to 10.7% in control group. Positive
      culture for Bacteroides and Mobiluncus was connected with nonstatistical rise in
      the risk of preterm delivery. No association between C. trachomatis infection at
      early pregnancy and elevated risk of preterm delivery was found. Early pregnancy
      diagnosis of bacterial vaginosis and its treatment should lower the rate of
      prematurity in Poland.

PMID- 14702671
TI  - [Susceptibility and frequency of selected groups of bacteria isolated in 2001
      from patients at the Holy Cross Cancer Center].
AB  - The aim of the presented study was the analysis of microbiological data obtained
      from patients hospitalized in The Holly Cross Cancer Center in Kielce in 2001.
      The frequency of important nosocomial pathogens in selected specimens and their
      susceptibility to antibiotics were determined. The strains were identified by
      using commercial tests (bioMerieux) and their antibiotic susceptibility patterns
      were performed by disc diffusion technique. The most prevalent bacteria were Gram
      negative rods of Enterobacteriaceae family (43%), mainly Escherichia coli. Only
      2.7% strains of isolated Escherichia coli isolated from clinical specimens
      collected from hospitalized patients were beta-lactamase--positive (ESBL+). The
      second important group of microorganisms were Staphylococci, followed by
      Enterococcus spp., Pseudomonas aeruginosa and Candida spp. About twenty eight
      percent of Staphylococcus aureus isolates were resistant to methicillin.

PMID- 14702672
TI  - Global situation of the HIV/AIDS pandemic, end 2003. Part II: Estimating ARV
      global treatment needs (2003-2005).

PMID- 14702673
TI  - [Radiological risk factors of bilaterality in unilateral slipped capital femoral
      epiphysis].
AB  - The aim of the study was to determine radiological risk factors of development of
      secondary contralateral slip in patients with primary unilateral slipped capital
      femoral epiphysis (scfe). The material consisted of 115 patients operated because
      of scfe in the Institute of Orthopaedics and Rehabilitation at the University of
      Medical Sciences of Poznan in 1968-1991. There were 75 boys (65%) and 40 girls
      (35%) at the mean age 12.8 years. The retrospective analysis showed that
      contralateral slip developed more often in patients with more vertical
      orientation of subcapital growth plate (with Alsberg angle less than 60 degrees).
      The neck-shaft angle, slip angle, slip direction and negative Klein's sign has no
      prognostic value according to development of secondary contralateral slip. More
      than 1/3 of the patients with unilateral scfe developed silent, subclinical
      contralateral slip. In most of that patients radiological signs of preslip stage
      of contralateral slip can be observed (positive Klein's sign, pathological neck
      epiphyseal angle).

PMID- 14702674
TI  - [Subacute osteomyelitis in children].
AB  - The paper presents diagnostic and therapeutic procedures in subacute
      osteomyelitis in children, basing on Robert's classification. The analyzed
      material consists of 11 children (aged 2 to 14 years) treated between 1990 and
      2000. Particular attention was given to signs and symptoms before full diagnosis,
      the clinical picture and to laboratory findings. Diagnostic difficulties were
      related to radiological similarities in subacute osteomyelitis and certain
      neoplastic processes. The authors stress the fact that non-invasive diagnostics
      are not sensitive enough for a definite diagnosis. Surgical treatment allows a
      histological confirmation and proper treatment.

PMID- 14702675
TI  - [The value of autologous osteochondral paste for in-vitro treatment of damage to
      articular cartilage. Part I. Macroscopic and microscopic assessment of the
      regenerated articular surface].
AB  - The limited ability of articular cartilage to regenerate after trauma has been
      the main reason for research of new repair techniques. The aim of this paper was
      to assess in in-vitro conditions the value of autologous osteochondral of pulp-
      macroscopic analysis of the regenerated articular surface and microscopic
      assessment of the dominant tissue in the regenerate. The experimental model
      consisted of a full-depth cartilage defect of the articular surface of the distal
      femur in rabbits. The animals were subdivided into 3 groups: group A--with defect
      with osteochondral of pulp, group B--with defects filled with osteochondral of
      pulp covered by periosteum, group C--defect untreated. After observation periods
      of 4, 8 and 12 weeks the regenerates were assessed using the Brittberg and
      O'Driscoll scale. In the overall macroscopic assessment group A prevailed because
      of the best defect filling. Microscopic assessment showed that in group A the
      defect had been filled with cartilage very similar to hyaline cartilage (hyaline-
      like cartilage). Basing on the result of the experiment, we assume that
      osteochondral of pulp has chondrogenic properties.

PMID- 14702676
TI  - [Frequency of neurological complications connected with transpedicular spine
      fixation].
AB  - To asses a frequency of neurological complications concerned with transpedicular
      spine fixation 1127 inserted transpedicular screws were reviewed. Penetration of
      pedicle was found in 5.5% of inserted screws. Radicular symptoms accompanied 0.8%
      of screw insertions. Complications were concerned only to medial or subpedicular
      penetrations. Highest number of potentially hazardous medial wall penetrations
      was found in lower lumbar spine. Treatment consisted of removal and repositioning
      of screws but with direct visualisation in cases with self tapping screws
      systems. The results shows that rate of neurological complications during
      transpedicular fixation is small and procedure is relatively safe.

PMID- 14702677
TI  - [Analysis of results of treatment of hallux valgus by Dega osteotomy].
AB  - The evaluation included sixty eight feet (forty one patients) treated with Dega
      osteotomy for hallux valgus deformity. Patient's average age at the time of
      surgery was 47 years (ranging from 11 to 65). The average duration of follow-up
      was 4.5 years (ranging from 2 to 10). The clinical and X-ray examination found
      good results in 29% of cases, fair results in 59% and poor results in 12% of
      cases. Fair results were associated with persistent wide forefoot and shortening
      of first metatarsal bone. Poor results were associated with persistent valgus
      deformity of hallux, jatrogenic hallux varus (2 cases), shortening of first
      metatarsal bone amounting to more than 1.0 cm.

PMID- 14702678
TI  - [Intrathecal baclofen for treatment of spasticity in patient with cerebral palsy-
      a preliminary report].
AB  - Spasticity is a common symptom of upper neuron damage which requires continuous
      research for new treatment strategies. The aim of this paper is to present the
      result of intrathecal baclofen infusion in treatment of spasticity in patients
      with cerebral palsy. Three patients (aged 16 to 21 years) in whom baclofen pumps
      were implanted underwent clinical and neurophysiological assessment both before
      and after pump implantation. Early results of spasticity treatment in cerebral
      palsy with intrathecal baclofen infusions are very promising.

PMID- 14702679
TI  - [Flexible flatfoot in children--a controversial subject].
AB  - In this review article authors present current opinion on flexible flatfeet in
      children. In young generation the incidence of flexible flatfeet is different
      according to investigator and evaluation method and ranges from 3 to 90 percent.
      The high percentage of appearance of flatfeet in healthy population is recognized
      mainly by investigators who are not orthopaedic surgeons. The flexible flat foot
      in children can be divided on developmental and static. The first one is visible
      in children immediately after starting walking and disappears spontaneously. The
      second one is associated with generalized but not pathologic soft tissue laxity.
      It is confirmed, that both do not need treatment. Nevertheless, the tendency for
      over-treatment of deformity by exercises, inserts and special shoes is observed.
      This kind of treatment results in costs and low effectiveness as well as
      psychological problems in patients. Persistent deformity does not cause worse
      quality of life in adulthood. Flexible flatfeet can be associated with shortening
      of the gastrocnemius muscle or even Achilles tendon. It results in valgus
      deformity of the hindfoot as compensation for the lack of dorsal flexion of the
      foot in the ankle joint. This deformity can be treated surgically.

PMID- 14702680
TI  - [The economic impact of hand injury].
AB  - Basing on 170 cases treated at the II Surgery Department of the Medical Faculty
      of Krakow University, the authors have tried to assess the direct and indirect
      costs of treatment of hand injuries. The rates negotiated between the Malopolska
      NHS Provides and the University Hospital were analyzed in order to assess direct
      treatment costs of hand injuries. Indirect cost assessment was based on analysis
      of insurance costs sustained by insurance providers. The analysis showed that
      over 96% of total treatment costs are indirect expenses related to compensation,
      work absence and disability pensions. The costs could probably be extensively
      reduced if hand injuries were referred directly to specialized surgery units.

PMID- 14702681
TI  - [Hyperplastic callus formation in patients with osteogenesis imperfecta].
AB  - The paper present a child with osteogenesis imperfecta in whom hyperplastic
      callus formation after a femur fracture and also after an osteotomy with
      intramedullary nailing of the tibia. An overview of available literature, with
      special attention given to differentiation with a malignant neoplasm is also
      presented.

PMID- 14702682
TI  - [Vertebroplasty in treatment of pathological fractures of the lumbar spine].
AB  - The authors present the results of 6 cases of lumbar vertebroplasty in the
      treatment generalized neoplastic disease. In the analyzed group there were 4
      females and 2 males (average age: 57 years). In all cases vertebroplasty was
      performed because of pathological fracture of vertebral bodies and consequent
      untreatable lumbar pain in. Pain was assessed directly before surgery, 5 days and
      8 weeks post-op. using VAS (Visual Analog Scale) and the Oswestry Back Pain
      Disability Index. In 4 cases major pain relief was noted, while in 1 case
      moderate pain relief was noted and in 1 case pain symptoms remained unchanged
      after the procedure.

PMID- 14702683
TI  - [Letter to the editor].

PMID- 14702684
TI  - [Benefit of microwaves in case of heat-sensitive agglomerate drying].
AB  - The microwave assisted vacuum drying of heat-sensitive materials is increasing in
      the pharmaceutical industry since the eighties. This paper deals with results of
      two experiment series obtained on a laboratory scale single pot dryer (Collette
      Ultima 251). Firstly water was heated up to the boiling point exclusively by
      predetermined microwave energy and then by various wall temperatures in order to
      determine the convection efficiency of the system. The experiments were carried
      out at fixed pressure level (80 mbar) and with optimum bowl load (15 kg).
      According to the demonstrated idea each single pot system efficiency can be
      specified at any type and quantity of load. With the help of the presented
      results the second experiments were designed to compare the microwave and
      convection efficiency of the single pot system during granule drying. A placebo
      granule was dried either by an exclusive convection or microwave method up to the
      determined LOD (< 0.5%). According to the tests extreme high wall temperature (85
      degrees C) had to be used to achieve the same drying time--and efficiency--as
      with the usage of dielectric heating. Based on the results it can be stated that
      the shorter drying time under favourable conditions is the advantage of microwave
      radiation over the conventional technique.

PMID- 14702685
TI  - [Preparation and structural determination of lyotropic lamellar liquid
      crystalline systems of pharmaceutical importance]].
AB  - Lamellar lyotropic liquid crystalline systems are thermodynamically stable,
      optically isotropic continuous compositions composed of particles of a few
      nanometeres in diameter which are formed spontaneously or with a low energy input
      in the definite proportions of the given components [8, 27]. New possibilities
      for the development of controlled drug delivery systems are inherent in these
      systems in consequence of their stability and special, skin friendly structure
      [3]. The present aim was to formulate and study two- or multicomponent
      compositions with a relatively low surfactant content, composed of materials
      official in the pharmacopoeia and suitable for therapeutic purposes. Macroscopic
      examination of the samples was carried out, together with polarizing light
      microscopy [5, 28] and transmission electron microscopic observation of replicas
      produced by the freeze-fractured technique [29-31] for the purpose of
      demonstrating the presence of lamellar liquid crystalline domains. The
      interlamellar repeated distance confirming the existence of a regular structure
      was determined by means of X-ray diffraction [26, 32].

PMID- 14702686
TI  - [Comparison of Echinops species on the basis of the monosaccharide composition of
      polysaccharides].
AB  - The goal of our investigation was to compare the monosaccharide composition of
      polysaccharides of different Echinops species. The determination of monosaccharid
      composition was made after Taylor reduction, acidic hydrolysis, reduction with
      sodium borohydride and acetylation in pyridine/aceticanhydride as alditol
      acetates with gas chromatographic analysis. 4-O-methyl-glucuronic acid was found
      in all studied species. The best similarity was found in the case of the
      monosaccharide composition of E. ruthenicus and E. exaltatus where rhamnose and
      arabinose are the main monosaccharides and 4-O-methyl-glucuronic acid is the
      uronic acid component. The main monosaccharides are glucose in E. orientalis and
      glucose and mannose in E. commutatus. Glucuronic acid is the uronic acid
      component in both species.

PMID- 14702687
TI  - [The effect of surface phenomena on the processing of solid materials. I.
      Theoretical basis of surface phenomena of solid materials].
AB  - The functions of friction and adhesion in the processing of solid materials were
      evaluated in our work. The first part of our study dealt with the theoretical
      basis of these phenomena. The work of Podczek was used as a guideline. The
      negative and positive effects of these parameters were emphasized. The types of
      adhesion were discussed. The different types of forces (capillary, Lifshitz-van
      der Waals, electrical, etc.) and several other parameters (surface free energy,
      roughness, particle size and shape) causing these effects were analysed.
      Different mathematical models which can be used for the determination of surface
      free energy, adhesion force and spreading coefficient were considered.

PMID- 14702688
TI  - [The effect of surface phenomena on the processing of solid materials. II.
      Experimental evaluation of surface phenomena of solid materials].
AB  - The functions of friction and adhesion in the processing of solid materials were
      evaluated in our work. The second part of our study dealt with some practical
      examples from our practice. Indomethacin was used for the examination of
      adhesion, dimenhydrinate for the study of friction, and metronidazole for the
      determination of the spreading coefficient. Several technological methods
      (coating, granulation, pelletization and tableting) were used. The positive
      effects of the processes on the various phenomena (surface free energy, adhesion
      force and spreading coefficient) were emphasized. The influences of alteration in
      the parameters on the flowability, compressibility, compact texture, etc. were
      assessed.

PMID- 14702689
TI  - [Laboratory studies of the antioxidant effect and free radical elimination of CoD
      tea].
AB  - Free radical elimination properties of anticarcinogenic CoD tea were studied in
      vitro in our laboratory. Therefore its antioxidant effect, lipid-hydroperoxide
      elimination property and reductive capacity were measured. The isoenzyme
      composition of CoD tea lipoxygenases was deduced from pH dependence of its
      lipoxygenase activity. It was found that the antioxidant effect and lipid
      hydroperoxide elimination property of CoD tea were comparable with those of
      ascorbic acid and the reductive capacity of a cup of CoD tea and 11-13 mg
      ascorbic acid were the same. In spite of the heat sensibility of lipoxygenases, a
      strong lipoxygenase activity (1102 U/g) of CoD tea was detected in acidic medium
      (pH 4.5). It is supposed that these free radical elimination properties support
      anticarcinogenic effect of CoD tea.

PMID- 14702690
TI  - [Photodynamic inactivation of porphyrin sensitized T7 phages: efficiency and
      mechanism of action].
AB  - We investigated the efficiency and the mechanism of action of two glycoconjugated
      tetraphenyl porphyrins in their photoreaction with T7 bacteriophage. Both types
      of porphyrins sensitized the photoinactivation of T7, but the slopes of
      inactivation kinetics were markedly different. Our result suggests that both type
      I and type II reaction play a role in the virus inactivation. Optical melting
      studies revealed structural changes in the protein part but not in the DNA of the
      photo-chemically treated nucleoprotein complex. Polymerase chain reaction (PCR)
      analysis failed to demonstrate any DNA damage.

PMID- 14702691
TI  - [Biological and chemical properties of alkyl lead derivatives].
AB  - This paper summarizes the chemical properties, analytical, biological and medical
      aspects of alkyl derivatives of lead used as anti-knocking agents in gasoline.
      The metabolism, clinical signs and symptoms are also shown. The possible
      treatments of patients will also be discussed in details.

PMID- 14702692
TI  - [Liposomes in gene therapy].
AB  - The role of liposomes in gene therapy is surveyed. The liposome mediated gene
      transfer is assessed. Details are given on the properties of cathionic lipids,
      and attributes of the cathionic vesicules. Problems and solutions animal
      experiments and human researches are discussed on literature examples.

PMID- 14702693
TI  - [The generic Research and Development possibilities after Hungary accessed th
      European Patent Convention].
AB  - January 1, 2003 Hungary became a member of the Munich Convention on the Grant of
      European Patents (European Patent Convention, EPC). As from January 1, 2003
      European patents may be claimed and obtained also for Hungary and European
      applications may be filed with the Hungarian Patent Office as well. This paper
      focuses on the exceptional generic R&D possibilities which can harmonize in
      harmony with all the claims of the Union in spite of the fact that it does not
      follow general European limitations and practises. Based on the amended Hungarian
      Patent Law (No. XXXIII of 1995 on the Protection of Inventions by Patents;
      Article 19 (6)b)) the exclusive right of exploitation shall not extend to acts
      done for experimental purposes relating to the subject matter of the invention,
      including experiments and tests necessary for the registration of medicines as
      well. The national and international legal history and background of the
      operative Hungarian Patent Law are also presented roughly. The paper deals with
      the divergence of the originator-generic industry and the EU-USA industry and
      with the incoherence within the EU itself on the early testing permissions and
      limitations.

PMID- 14702694
TI  - [Utilization and comparison study of antipsychotics at the Department of
      Psychiatry and Psychotherapy of the Semmelweis University and the Galfi Bela
      Hospital].
AB  - The authors examined the use of antipsychotics at the Department of Psychiatry
      and Psychotherapy of the Semmelweis University and at the Galfi Bela Hospital by
      reviewing retrospectively the drug ordering practice in the period of 1998-2002.
      The aim of the study was to analyse the utilization aspects of the use of
      antipsychotic medication. The study also aimed to identify the main trends of
      prescribing preference and to compare the use of antipsychotics in the two
      institutions. Data showed that in accordance with the latest professional
      guidelines the use of novel antipsychotics is increasing. Based on analysis of
      the antipsychotic use in both clinical practices there were characteristic
      patterns found that show that the conventional antipsychotic use is still
      notable. The purpose of the present study was to follow the temporal development
      trends and present state of antipsychotic use which could result in a cost
      effective drug therapy.

PMID- 14702695
TI  - [Tuberculosis's incidence in Romania in the year 2002].

PMID- 14702696
TI  - [Characteristics of bronchial inflammation in children with chronic non
      productive cough].
AB  - The aim of study was to correlate the bronchoalveolar lavage (BAL) cell
      subpopulations in light microscopy and clinical-functional parameters in 20
      children with chronic nonproductive cough (potentially evolving to asthma) in
      comparison with 20 children with mild and moderate stable asthma. The results
      revealed a different BAL cell profile of chronic coughing children, characterized
      by a lower percent of total cells (0.279 +/- 0.055 x 10(6)/ml), eosinophils (0.97
      +/- 0.80%), lymphocytes (6.02 +/- 0.85%) and epithelial cells (28.52 +/- 5.15%)
      and higher percent of macrophages (46.05 +/- 7.94%) and neutrophils (18.27 +/-
      4.93%). Eosinophilic inflammation in BAL and bronchial hyper-responsiveness (PC20
      methacholine = 1.73 +/- 0.15 mg/ml) were revealed in three cases with chronic
      cough. Based on these reasons, they were included in "cough variant asthma". In
      conclusion, children with nonproductive chronic cough represent a heterogenous
      group, with different underlying causes. Only a minority of these patients has
      "cough variant asthma", with a favorable response to inhaled corticotherapy.

PMID- 14702697
TI  - [Early diagnosis of lung cancer in Constanta county--preliminary results].
AB  - Lung cancer (LC) has an increasing incidence and mortality rate in both sexes in
      Romania. Due to its gravity, early detection of LC (stages 0, I, II) is very
      important. We analyzed a group of 161 patients with LC. Early LC was present in
      22% (36 patients). More than half of them were in stage II. All patients had high
      risk for LC: smokers, man, and age over 50. Suggestive symptomatology of early LC
      included: cough and its change of pattern, hemoptysis and loss of weight. In 95%
      of these patients radiological abnormalities were already present. Bronchoscopy
      (including biopsy brushing, bronchial aspiration and bronchial washing) was the
      main diagnostic procedure for central type LC, but was also useful in peripheral
      type. Sputum analysis was positive in 92% of cases. Early detection of LC needs
      an active diagnosis in all patients with high risk, with all available diagnostic
      procedures (including high resolution computed tomography).

PMID- 14702698
TI  - [Smoking habits: a study of Iasi school staff].
AB  - AIM: To asses the frequency of smoking habits among the school staff from Iasi.
      METHODS: An anonymous questionnaire with 21 items was administrated to 675
      subjects (165 were male and 510 were female) who had performed periodic chest X
      ray control during September 2001. The mean age of the group was 42.5 years.
      RESULTS: 41.8% of the men never smoked, 17.5% were ex-smokers and 40.6% regular
      smokers. The same rate in women as follow: 68.8%, 6.6%, 24.5%. The age for
      beginning smoking in women (18-20 years) was significantly higher than that in
      men (14-15 years). The highest prevalence of tobacco smoke was found among
      auxiliary personnel men (47.5%) and teachers women (28.2%) and the lowest among
      kinder garden teachers men and women (18.2% and 21.3%). Despite of the fact the
      majority of smokers had knowledge about smoking relationship with chronic
      bronchitis (85.4%-85.1% men and 85.6% women), lung cancer (87%-89.2% male and
      85.6% female) and cardiovascular diseases (84.3%-88.1% men and 82.4% women),
      55.2% of all smokers (53.7% male, 56% female) had never tried to quit smoking.
      CONCLUSIONS: It is obvious that the rules on smoking restriction in Romania
      schools are needed.

PMID- 14702699
TI  - [Anaerobic bacteria in lung suppurations. Etiologic and pathogenic aspects].

PMID- 14702700
TI  - [Idiopathic pulmonary hemosiderosis in adults].

PMID- 14702701
TI  - [Induced sputum-- a way to monitor inflammation in bronchial asthma].

PMID- 14702702
TI  - [Multiple primary cancers with different localizations and histologic types.
      Clinical case].
AB  - The authors describe the case of male patient of 46 years old, which was
      diagnosticated with 4 cancers of different localization and histopathological
      types in the course of 6 years. In chronological order these 4 neoplazias were:
      the Hodgkin's disease with mixed cellularity, the malign parieto-frontal right
      meningioma, a Grawitz renal tumor and a lung adenocarcinoma with bilateral lung
      and pleural metastasis. For both cerebral and renal tumors the patient was given
      a surgical treatment and for the Hodgkin's disease and lung cancer given
      chemotherapy and cobalt therapy.

PMID- 14702703
TI  - [Atrial myxoma: a challenge for the pneumologist].
AB  - It presents a 59 years old woman with atypical symptoms, which orientated the
      diagnostic thinking during one year to a reccurrent pneumonitis, bronchial
      asthma, colagenosis, interstitial pulmonary fibrosis and so on. The appearance of
      pulmonary edema determined a couple of cardiologic exams which came to
      obiectivate as the main cause, the existence of a left atrial mixoma who was
      invaginated in left mitral cusp. Surgical intervention permitted not only
      specific determination of histological type of tumor, but lead to healing of the
      patient. It is a discussion over epidemiology, clinical areas of manifestation
      and methods of diagnostic of atrial tumors.

PMID- 14702704
TI  - [Involuntary smoking and the risk for cancer].

PMID- 14702705
TI  - [Law 349/2002-consequences on medical activity].

PMID- 14702706
TI  - [Pulmonary involvement in breast and genital cancers].

PMID- 14702707
TI  - [Current indications of surgical treatment in lung tuberculosis].

PMID- 14702708
TI  - [Rewarded diagnostic perseverance].

PMID- 14702710
TI  - [In focus : pediatric pneumology].

PMID- 14702709
TI  - [Controversies in the treatment of non-small lung cancer].

PMID- 14702711
TI  - [The current situation of extrarespiratory tuberculosis in Romania ].

PMID- 14702712
TI  - Some epidemiological and socio-medical peculiarities of pulmonary tuberculosis
      (pTB) among individuals from war affected areas (WAA)--experiences and results
      from north-west Yugoslavia (NWYU).
AB  - AIM: 1. To find out the differences between patients (pts) from WAA and the
      general population (GP) suffering from pTB. 2. To evaluate the proportion and
      characteristics of pts from WAA in pulmonary TB (pTB) hospital mortality rate. 3.
      To evaluate how many refugees (RE) and displaced persons consider TB as a social
      "stigma". METHODS: 1. Analysis of the medical files of pts with pTB--137 from WAA
      and 212 from the GP. 2. Analysis of clinical data of pts who died of pTB from
      1990 to 1999. 3. A questionnaire about knowledge and social attitude towards TB.
      RESULTS: 1. The main characteristics of pts with pTB from WAA (both those who
      were dismissed from hospital and those with fatal outcome) are: male dominance,
      prolonged hospital treatment, high prevalence of relapses, very extended forms of
      the disease and presence of cavernous lesions on chest X-ray. 2. Deterioration of
      life conditions, impoverishment, demographic changes, shortage of anti-TB drugs
      and supplies for diagnosis led to increase hospital mortality rate of TB between
      1990 and 1999 in NWYU (36% of all pts who died of TB in the mentioned period
      originated from WAA). 4. RE from former Yugoslavia consider TB more as a social
      "stigma" than the GP. CONCLUSION: The prevention, treatment and follow up of pts
      with pTB from WAA must be a priority in the Yugoslav national TB programme.

PMID- 14702713
TI  - [Success rate in patients with lung TB registered in Brasov county between 1990
      and 2001].
AB  - The purpose of the present study was to assess the success rate of TB pulmonary
      cases registered in the district of Brasov between 1 january 1990-31 December
      2001 and followed from 0 to 154 months. The retrospective study for 1990-1994 and
      prospective for 1995-2001 included 4369 pulmonary cases over 14 years in age,
      respectively 3912 new and 587 relapsed cases. To these patients were analysed the
      favorable and unfavorable evolutions, including relapses cases. The evaluation of
      the first treatment after National TB Program's 2001-2005 standards showed 2893
      favorable evolutions, respectively 1612 (42.4%) cured and 1281 (33.7%) completed
      treatment and unfavorable evolutions 795 cases: 284 failures (7.5%), 345
      defaulters (9%) and 166 TB deaths (4.4%). To these were associated 224 (5.9%)
      relapses cases appeared after 12 months from the begining of the treatment.
      Between relapses cases were analysed as favorable evolutions 332 cases
      respectively 207 (36.6%) cured and 125 (22.1%) completed treatment and
      unfavorable evolutions 217 cases: 68 failures (12%), 118 defaulters (20.9%) and
      31 TB deaths (5.5%). To these were associated 38 (6.7%) relapses cases appeared
      after 12 months from begining of the treatment. An age group of new cases with
      the highest percentage of the favorable evolutions, respectively 89% (p < 0.001)
      at women was 15-24 years and for the unfavorable evolutions, respectively 33% at
      men was 35-44 (p < 0.05) and over 65 years. The comparison on the bacteriological
      categories between new and relapses cases showed that the percentage of the
      favorable evolutions was significantly higher at new-cases. At new cases after 12
      years of supervision, the rate of success varied a little and registered the less
      value of 77% at 9 years of monitoring, and finally a level of 78.5%. At relapses
      cases, after a diminution in the first 3 years until 59.2%, the value bring up
      year after year and registered a peak of 72.4% at 8 years of monitoring. After 12
      years, the rate of success of the first retreatment was 58.8% representing the
      less level of the whole interval. For the new cases at the first treatment the
      risk of failure was 8.6%, default 10.3% and tb death 5% and for the relapses
      cases at the first retreatment the risk of failure was 15.8%, default 25.2% and
      TB death 7.2%. The risk of relapse for new cases varied between 2.9% at 2 years
      and 1% at 10 years, and for the relapses cases between 6.1% at 2 years and 1%
      after 8 years of monitoring. The preoccupation for augmentation the level of the
      success of the first treatment might improve the performances on the long time in
      tuberculosis control.

PMID- 14702714
TI  - [Non-invasive ventilation, a revolution in the therapy of chronic respiratory
      failure and sleep apnea syndrome].

PMID- 14702715
TI  - [Etiology, diagnosis, and treatment of pulmonary histiocytosis].
AB  - Langerhans' cell histiocytosis (LCH) encompasses a group of disorders with
      variable clinical features and prognosis that share in common the infiltration of
      involved tissues by numerous Langerhans' cell (LC), often organized in
      granulomas. In adults, pulmonary involvement with LCH is observed predominantly
      in young cigarette smokers. Lung involvement is usually an isolated or a
      predominant manifestation, and is characterized by LC granulomas entered on
      distal bronchioles. HRCT has proved to be very useful in the diagnosis of
      pulmonary LCT, showing in typical asess the association of nodules, cavitary
      nodules and cystic lesions with both thick and thin walls. The definite diagnosis
      of pulmonary LCT generally requires lung biopsy. The pathogenesis of pulmonary
      LCH is not well understood.

PMID- 14702716
TI  - [Fenspiride-a new alternative on the therapy of obstructive lung disease].

PMID- 14702717
TI  - [Early and differential cytologic diagnosis in lung cancer].

PMID- 14702718
TI  - [Wegener granulomatosis--a case report].
AB  - The Wegener's granulomatosis is characterized by the involvement of the upper
      airways, the lower airways and the late involvement of the kidneys. The authors
      are presenting in this article, the case of a 44 years old man, which presented
      the three conditions mentioned above, with an early kidney involvement and who
      died due to a major complication of the disease: the intravascular disiminated
      coagulation and a multivisceral vascular involvement, despite the correct and
      early treatment.

PMID- 14702719
TI  - [Prevalence of bronchial asthma in 7 years -old children in Cluj-Napoca, an ISAAC
      study].
AB  - The authors studied the prevalence of asthma in children of 7 years from Cluj
      Napoca and analyzed the possible risk factors. We used the questionnaire
      elaborated by International Study on Asthma and Allergic Diseases in Children
      (ISAAC) which allowed the comparison of our data with those from other countries.
      Anamnesis, functional tests and allergic skin tests were performed in children
      with positive answers for questionnaire. 1334 children completed the study, 52.5%
      being males. Prevalence of asthma diagnosed previous to the questionnaire was of
      5.7%, and it was higher in males (6.1%). By anamnesis, functional and skin tests
      data the diagnosis of asthma was made in a total of 217 children, so that the
      real prevalence of asthma is of 16.3% in this age group. Maternal smoking during
      the first year of life was significantly higher in children with wheezing. The
      high number of respiratory tract infections in the first year of life could also
      play a role. In conclusion, prevalence of asthma diagnosed in children of 7 years
      of age from Cluj Napoca is of 5.7% with a real prevalence of disease that seems
      to be much higher, of 16.3%. Maternal smoking represents a risk factor correlated
      with wheezing.

PMID- 14702720
TI  - [Recurrent wheezing in infants and small children].

PMID- 14702721
TI  - ["Smoke free hospitals"--an European project for the future].

PMID- 14702722
TI  - [Multiple air-liquid pulmonary images].

PMID- 14702723
TI  - [Treatment of pleural effusions by pleurodesis].

PMID- 14702724
TI  - [Imagery in secondary glaucomas diagnosis].
AB  - The purpose of this study was to present the actual performances of the imagistic
      techniques for the complete investigation of secondary glaucoma. For this aim
      there were selected patients from the Ophthalmologic Clinic Cluj-Napoca. They
      have been submitted to ultrasound investigations, fluorescein angiography and
      magnetic resonance imaging techniques. Ultrasound techniques: A-scan, B-scan and
      Doppler allow to track and discriminate the ocular and orbital diseases which can
      offer the bases of correct diagnosis in secondary glaucoma. The color Doppler
      assures a good visualization of neovascularization, tumoral vascularization,
      arterio-venous abnormalities. Magnetic resonance imaging completes the data
      obtained by ultrasound and fluorescein angiographique techniques. The imagistic
      techniques associated with the clinical features offer the bases of the
      diagnostic and proper therapy in secondary glaucoma.

PMID- 14702725
TI  - [Controversy about the term inflammatory orbital pseudotumor].
AB  - The term of "inflammatory orbital pseudotumor" is met in the inflammatory
      pathology of the orbit and it has been modified through the time both in its
      frequency of usage and in its meaning. The authors make a review of the evolution
      of in the term usage and especially in its importance as a partial diagnosis and
      also as an attitude towards the paraclinical investigations. The goal of this
      work is to present the evolution of the problems implied by the term "orbital
      pseudotumor" that even today rises controversies.

PMID- 14702726
TI  - [Birdshot retinochoroidopathy].
AB  - Birdshot retinochoroidopathy is a rare, chronic, bilateral, posterior uveitis
      with a distinctive clinical presentation and a strong genetic association. Middle
      aged white people of northern European extraction are most commonly. The
      pathogenesis is unknown, but HLA-A29 positivity appears to confer predisposition
      and retinal autoimmunity seems to play a role. Clinically, there are patches of
      postequatorial choroidal and retinal pigment epithelial depigmentation, vitreal
      cells, macular and disc edema, and venous sheathing. This review provides an
      updated summary of the current state of knowledge about birdshot
      retinochoroidopathy. It includes results of visual field and electrophysiological
      tests.

PMID- 14702727
TI  - [Coats disease].
AB  - Coats disease is an idiopathic disorder characterized by an abnormal development
      of retinal vessels (telangiectasia), with a progressive deposition of
      intraretinal or subretinal exudates, leading to exudative retinal detachment.
      Classically is isolated, unilateral and affects mainly boys between 4 to 8 years.
      The diagnostic methods include direct and indirect opthalmoscopy, fluorescein
      angiography, ultrasonography, CT scan, MR imaging, especially in the advanced
      stages of disease, when is difficult to differentiate from retinoblastoma. The
      treatment includes laser therapy of abnormal leaking retinal vessels and
      cryotherapy in early stages, more advanced stages require surgical techniques of
      retinal reattachment. Stabilization of the disease course or clinical improvement
      can be achieved using a carefully selected therapy.

PMID- 14702728
TI  - [Branch retinal arterial occlusions--clinical case].
AB  - Branch retinal arterial occlusion is an ophthalmological emergency, presenting
      with features of sudden and painless loss of vision and visual field defect. Even
      if the diagnosis is easy to make, the ophthalmologist is, most of the times,
      unable to improve the prognosis. We present a clinical case of unilateral branch
      retinal arterial occlusion with unusual evolution.

PMID- 14702729
TI  - Photochemical and photodynamic properties of vitamin B2--riboflavin and
      liposomes.
AB  - Ocular neovascular disease represents an important cause of blindness today. In
      this paper, it was used a model to evaluate the vaso-occlusive potential of
      photodynamic therapy with B2 vitamin. Neovascularization induced in an occular
      cornea consists of an easily accessible monolayer-like neovascular net within a
      transparent matrix. This fact allows studying the efficiency of occlusion in an
      isolated neovascular structure. This study is a requirement for the transport
      evaluation and photodynamic efficiency of this drug. Both riboflavin and the DPBF
      are embedded in the phospholipid bilayer. The quantum yield of DPBF
      photooxidation and riboflavin singlet oxygen generation are higher by comparison
      with water (13-35 s in liposomes and 0.4 s in water), due to the higher lifetime
      of singlet oxygen in liposomes and due to the special transport mechanism of B2
      inside of liposomes. The photochemical behavior of riboflavin (Vitamin B2)
      aqueous solution and in unilamellar liposomes of dipalmitoyl phosphatidylcholine
      (DPPC) during the sensitized photooxidation of 1,3-diphenylisobenzofuran (DPBF)
      are discussed in this paper. Some structural aspects of DPPC liposomes, have been
      studied, too. The first step in the sequence of vesicle shape transformations,
      the spherical to polygonal shape transition, occurs in a very narrow temperature
      range, i.e., during the gel-to-liquid crystalline phase transition. At different
      temperatures (30,37-42 degrees C) could be seen the sequence for the vesicle
      form: spherical-polygonal-ellipsoidal, attributable to the lipid domain
      coexistence on the macroscopic structure of liposomes. The incorporation of B2
      Vitamin eliminates the ellipsoidal form of DPPC, even at high temperature,
      because B2 has a very small molecule able to be encapsulated into DPPC vesicle.
      Also, the incorporation of B2 increase the DPPC diameter, all these observations
      being obtained by optical confocal microscopy.

PMID- 14702730
TI  - [Leukokoria. Diagnosis and treatment].
AB  - PURPOSE: Is to evaluate the importance of the imaging tests when the posterior
      segments of the eye cannot be visualized due the opaque ocular media. MATERIAL
      AND METHODS: The paper presents 50 patients with unilateral or bilateral
      leukokoria treated in the University Eye Hospital from Cluj-Napoca. The
      parameters who had been watched were: the visual acuity, ultrasonography of the
      eye, and the management of the lesions associated with leukokoria. The
      ultrasonography was indicated for the diagnosis of the conditions associated with
      leukokoria, using a transducer of 7.5 MHz. RESULTS: The conditions associated
      with leukokoria were: intraocular tumors in 8% of cases; congenital cataract in
      24% of cases; persistent hyperplastic primary vitreous in 2% of cases; complicate
      or pathologic cataract in 27% of cases; retinopathy of prematurity in 6% of
      cases; vitreous opacities in 33% of cases. In 30% of cases ultrasonography of the
      eye was normal. Echography is also important for the differential diagnosis of
      secondary retinal detachment. We found exudative retinal detachment in 20% of
      cases; in 28% of cases there was a tumor retinal detachment, in 44% a tractional
      retinal detachment, and in 8% a posterior vitreous detachment. The performed
      management was represented by: enucleation in 12% of cases; EEC in 21% of cases;
      EEC + sinechiolisis in 11% of cases; sinechiolisis in 2% of cases; vitrectomy in
      11% of cases; evisceration in 6% of cases; medical treatment in 20% of cases.
      CONCLUSIONS: Ultrasonography is an important imaging test for the diagnosis of
      the conditions associated with leukokoria. Taking into account echographic
      results the adequate treatment of the eye lesions can be established.

PMID- 14702731
TI  - Expanding masses of the posterior orbit.
AB  - The expanding masses of the posterior part of the orbit consist of the
      intraorbital space occupying processes, located posteriorly to the frontal plain,
      crossing the anatomic equator of the eyeball. Modern surgery of this part of the
      orbit is included in the larger field of the anterior skull base surgery.
      Successful orbital surgery is a multidisciplinary team work, based on precise
      preoperative diagnosis, adequate surgical technique and comprehensive anatomical
      knowledge of the operated region. This paper presents the experience of the
      authors on 73 cases of expanding masses of the posterior orbit, admitted and
      treated in the Neurosurgical Clinic from Cluj-Napoca.

PMID- 14702732
TI  - [Visual screening to discover ophthalmologic disorders in children].
AB  - PURPOSE: [corrected] To report the frequency of common childhood ocular disorders
      in a pediatric population. To address the issue of access to care for vision
      screening programs. METHODS: Prospective vision screening for a period of 2 years
      (February 2001-February 2003) which enroll 254 children from 3 villages
      (Ceplenita, Vladeni, Aroneanu) sponsored by World Vision Romania. The study asses
      refractive errors, strabismus, amblyopia and other ocular abnormalities. RESULTS:
      The mean age was 8.09 +/- 2.88 with the following distribution: preschool 19%,
      first grade 56%, second grade (over 10 years of age) 25%. Refractive errors
      requiring correction were observed frequently in this group of children
      (especially mild hyperopia, small myopia, astigmatic refractive errors).
      Strabismus was identified in 7.87% of cases and amblyopia in 11.42% (1/3 of cases
      mild and severe). CONCLUSIONS: The frequency of common visual disorders in this
      population sample was larger than previously published studies. In poor economic
      subgroups the first ophthalmologic examination was performed after school age.
      Access to care is an integral part of any vision screening program. We are trying
      to highlight the importance of effective follow-up programs for all children
      especially those with limited resources for health care.

PMID- 14702733
TI  - [Endothelial dysfunction in patients with open-angle glaucoma and atheromatous
      lesions].
AB  - A number of observations revealed that the haemodynamic alteration may contribute
      to pathogenesis of glaucomatous neuropathy. Endothelial dysfunction associated
      with atherosclerosis impaired the endothelial dependent vasodilatation. PURPOSE:
      To evaluate the relationship between the endothelial dysfunction (assessed by
      plasma NO level) and carotid stenosis degree in primary open angle-glaucoma
      patients. METHODS: Carotid ultrasonography and plasma NOx level (nitrite and
      nitrate) were obtained from 3 groups of patients: group 1-patients with primary
      open angle-glaucoma and carotid stenosis; group 2-patients with carotid stenosis
      and group 3-healthy subjects. RESULTS: A significant lower NO level (compared
      with group 3) and a significant higher carotid stenosis (compared with group 2)
      were found in primary open angle-glaucoma patients. There was a significant
      correlation between the NOx level and carotid stenosis. CONCLUSIONS: Assessing
      the carotid atherosclerotic plaques may be benefical for the patients with
      primary open angle-glaucoma. Pharmacological neuroprotection with NO precursors
      may be useful for the patients with carotid stenosis associated with primary open
      angle-glaucoma.

PMID- 14702734
TI  - [Clinical signs in vascular accidents of the retrochiasmatic pathways].
AB  - The purpose of this study was to determine the neuroophthalmologic signs which
      accompanies ischemic or hemorrhagic cerebral vascular accidents. This study was
      carried out on 110 patients, for three years. Most of the neuropathalmologic
      signs, such as hemianopic deficits, have accompanied the ischemic vascular
      accidents. Hypertension was the most frequent cause of this vascular damages. The
      neuropathalmologic signs were predominant at male, in comparison to female, in
      all the years studied. As the value of the etiological factory rise, rise also
      the incidence of the cerebral vascular damages accompanied whit
      neuropathalmologic signs.

PMID- 14702735
TI  - [Postoperative complications of refractive surgery, Lasik technique].
AB  - PURPOSE: To determine the postoperative complications of laser Excimer surgery,
      LASIK technique. MATERIAL AND METHOD: We studied 142 eyes with different
      refractive defects operated with laser Excimer. RESULTS: The early postoperative
      complications were: DLK stage 11/III--6 eyes, Hase--24 eyes, Epitelial Ingrowth
      in 2 eyes and Central Islands in 2 cases. Late postoperative complications were:
      secondary glaucoma after steroids administration in 1 case and subcorrection in
      19 eyes. CONCLUSION: A quickly treatment of postoperative complications after
      LASIK technique assure the estimated functional results.

PMID- 14702736
TI  - [Study of refractive changes inTimis.county].
AB  - The aim of the study was to assess the prevalence of common refractive errors in
      children investigated at the "Louis Turcanu" Hospital's Ambulatory from
      Timisoara. This was a cross-sectional study done from January to June 2002 in the
      Ophthalmologic Medical Office. The target group was those of children from Timis
      County. We examined 646 children with a mean age of 10.7 years (from 0 to 18
      years). A cycloplegic refraction examination was performed on all the children,
      using a computerized Humphrey-Zeiss autorefractometer. The statistical analysis
      was performed using CDC's Epi Info 2002. in the analysis, we used the Odds Ratio,
      the exact Fisher test and the chi-squared test. Among the 646 children, 407--63%
      (CI95 = 59.1-66.7) had refraction errors, of which 1.5% (CI95 = 0.8-2.9) were
      myopic whereas 49.8% (CI95 = 45.9-53.8) were hyperopic. Astigmatism was found in
      11.8% (CI95 = 9.4-14.6). The study showed higher prevalence for the 14-16 age,
      emphasizing the importance of these examinations.

PMID- 14702737
TI  - [Temporal contrast sensitivity in general population].
AB  - OBJECTIVE: To define the normal range of values for temporal contrast sensitivity
      (TCS) in the general population. MATERIAL AND METHOD: The study group consisted
      of 140 healthy subjects (280 eyes). Measurements were performed using a prototype
      designed to produce a red color flicker test (660 nm) with variable frequency and
      modulation, projected in the central visual field. We conducted test with 10, 20
      and 30 Hz with highest illumination level. Subjects have been grouped according
      to age decades as well as sex. Each group was separately evaluated for
      distribution type, mean and confidence interval. Statistical differences were
      assessed using ANOVA with one variable. RESULTS: No significant differences could
      be found between male and female subjects and the response pattern is very
      similar in all age groups. Temporal contrast sensitivity presents a normal
      distribution, with a limited dispersion of data around mean value for the
      respective decade. TCS slightly decreases with age but correlation parameters do
      not gain statistical significance. Normal range was defined for age decades using
      the S score, which quantifies the distance from the mean and as such compensates
      for the differences generated by the non-linear relationship between age and TCS.
      The test S < 0 defines pathological circumstances with a specificity of 96.5% at
      10 Hz, 99.3% at 20 de Hz and 95.4% at 30 de Hz respectively. CONCLUSIONS: We
      managed to establish normal TCS range of values for the general population using
      a test with a very good specificity. These normal values, obtained within a
      statistically significant group, represent the first step in using TCS in
      ophthalmologic research. Abnormal TCS changes can now be compared with normal
      values for each age group.

PMID- 14702738
TI  - [Refractive changes in concomitant exodeviations].
AB  - The paper represents the analysis of 27 patients with a form of exodeviation
      examined in the Department of Ophthalmology Sibiu (jan. 1999-jan. 2003). METHOD:
      The evaluated parameters were: debut age, sensorial status, refraction, type of
      exodeviation related with refractive errors and treatment. RESULTS: The
      predominant refractive error was hyperopia (low degree)-40.74%, exophoria was the
      most frequent type of exodeviation (44.44%). Amblyopia was present in 11.2% of
      cases, 25.9% of patients had no stereopsis. CONCLUSIONS: In the studied group
      81.48% of cases had refractive errors. Exophoria and intermittent exotropia were
      related with emetropia or minor refractive errors. Mixed astigmatism with
      amblyopia and anizometropia presented constant exodeviation.

PMID- 14702739
TI  - [Central serous chorioretinopathy and serous detachment of the pigmentary
      epithelium. Pathogeny relations].
AB  - A number of 7 cases of association of pigment epithelial serous detachment with
      central serous chorioretinopathy were described. The dye leakages were located at
      the periphery of the serous detachment (6 cases) and on its anterior surface (1
      case). These are due to RPE breaking, as a result of the tension exerted by the
      build up of choroidal exudate in the subretinal space. Given the circumstances,
      central serous chorioretinopathy is an atypical clinical type, subsequent to the
      alterations of the overlying pigment epithelium. This one is differing from the
      classic type, because of the wide area of the serous detachment and the
      peripheral location of the dye leakages.

PMID- 14702740
TI  - [Travatan--preliminary results].
AB  - PURPOSE: The prostaglandin analogues represent the first option for the treatment
      of primary open angle glaucoma. The aim of this paper was to evaluate the
      efficacy and the safety of Travatan in treatment for different type of glaucoma.
      METHODS: It was performed an observational clinical study between November 2002
      and March 2003 on 33 patients (62 eyes), who were divided into treatment with
      Travatan in 4 groups. RESULTS: The reduction of IOP was between 3.80-7.80 mm Hg,
      with 70.94% complete success (IOP < 18 mm Hg) and qualified success (IOP < 22 mm
      Hg) in 88.31% cases. CONCLUSIONS: Travatan was effective as single therapy or
      adjunctive therapy, with important and stable lowering IOP. The product was safe,
      well tolerated and easy for administration.

PMID- 14702741
TI  - [Yag-Nd posterior capsulotomy.When? Where? How?].
AB  - PURPOSE: To answer a few elementary questions raised when confronted with the
      patient with aftercataract: Which are the indications and counter indications of
      the posterior capsulotomy? How can be evaluated the degree of PCO (posterior
      capsule opacification)? Which are the ideal size and location of the capsular
      opening? Is it mandatory to dilate the pupil? What energies are to be used? Which
      would be the recommended follow-up pattern? METHOD: This paper is a retrospective
      analysis of the 956 posterior capsulotomies performed between January 2001 and
      December 2002 at Bucharest Eye Hospital, Ophthalmology III Clinic, Nd:Yag laser
      surgery department. RESULTS: The best outcome is obtained with the fewest
      complications when the following conditions are met: the capsulotomy is performed
      no sooner than 6 months postoperatively; the capsular opening is small--2 mm in
      diameter--but perfectly aligned relative to the pupil and the IOL (sometimes this
      is difficult to achieve and the surgeon must always bare in mind the geometry of
      the posterior chamber and the parallax effect); laser pulses have low energy and
      are posteriorly defocused; when energy higher than 2 mJ is employed, the
      capsulotomy is performed by applying punctures in a circular pattern instead of a
      crosslike rectilinear pattern (in the case of IOL pitting, the visual axis is
      spared). CONCLUSION: The Nd:Yag photodisruptive laser offers a swift, safe and
      elegant method for dealing with a common and disturbing complication of the
      modern cataract surgery, the posterior capsule opacification. The results are
      often spectacular from the patient's point of view, but one should not neglect
      the risks related to the posterior capsulotomy.

PMID- 14702742
TI  - [Modern treatment in venous retinal obstruction].
AB  - This article is a general view of modern methods of treatment in venous retinal
      obstruction. In the last years, medical treatment and LASER therapy have been
      replaced by early surgical approach. The main advantage of the last one is
      removal the cause of the disease not its effects.

PMID- 14702743
TI  - [Utilization patterns of CT and MRI in Israel].
AB  - BACKGROUND: One of the major factors contributing to the escalating increase in
      the costs of the health system is the accelerated utilization of health
      technologies such as Computed Tomography (CT) and Magnetic Resonance Imaging
      (MRI). Prior to this study in Israel, there was no available national database to
      ascertain the scope and utilization patterns of imaging technologies. A number of
      trends combine in the need to assess the utilization patterns in Israel. Firstly,
      imaging examinations constitute a larger and ever-growing predominate role in the
      diagnostic process. Secondly, these technologies can complement or supplement
      each other. Thirdly, the rising costs to the health system resulting from the
      numerous examinations conducted and finally, the importance of protecting public
      health from the damage caused by exposure to radiation during CT examinations.
      OBJECTIVES: 1. To describe the utilization patterns for CT and MRI examinations
      in Israel. 2. To compare the consumption of imaging services with that of other
      Western countries. METHODS: The initial stage was to identify all the
      institutions operating CT or MRI devices. Data was collected by means of a
      questionnaire from these organizations on the extent of use, characteristics of
      the utilization patterns, indications, accessibility, availability, and referents
      etc. during the period 1995-1999. RESULTS: In the year 2000, 38 CT and 9 MRI
      devices were operating in Israel. We observed an increase in the number of CT and
      MRI examinations between the years 1995-1999 and a rise in the level of
      examinations per 1,000 population. The rate of MRI examinations per person in
      Israel was found to be lower in comparison to other Western countries. Upon
      analysis of the distribution of indications it was found that approximately 37%
      of the CT examinations were cranial examinations and 18% were spinal
      examinations. In MRI examinations 38% were cranial and 30% spinal tests.
      CONCLUSION: The rising trends in the rate of CT and MRI examinations during the
      period 1995-1999 and their characteristics, match the comparable rise witnessed
      in most Western countries in recent years. Although the level of CT and MRI
      devices per population in Israel is low in comparison to the Western world, the
      devices operate intensively. In light of the high level of accessibility and
      availability of these imaging devices in Israel, the research findings
      corroborate the claim that the number of devices influences the scope of
      utilization and supports the supposition that these imaging devices are used
      efficiently in Israel.

PMID- 14702744
TI  - [Screening for depression in primary care clinics in Israel--how wide is the
      gap?].
AB  - Depressive disorders are common and cause substantial suffering, loss of
      productivity, and increased morbidity and mortality. Nonetheless, it is
      frequently cited that the disorder is under-diagnosed. In this article we
      examined the utility of a two phase case detection strategy for depression in
      primary care clinics in Israel. We compared screening findings with the medical
      charts diagnoses. A three-question screening test for depression taken from the
      Diagnostic Interview Schedule (DIS) was answered by 551 primary care patients.
      Those who answered positively on one or more questions were asked to answer a
      more specific and detailed questionnaire in order to detect depression: The
      Inventory to Diagnose Depression (IDD). The results were compared with the
      diagnoses on the medical charts, and treatment for depression. In addition the
      number of visits to the primary care physician was compared, between depressed
      and non-depressed patients. The first questionnaire (from the DIS) was completed
      by 551 patients. A total of 222 (40%) of these patients gave at least one
      positive answer. Only 113 (51%) agreed to answer the second questionnaire (IDD).
      According to the IDD, 15 were depressed: 9 fulfilled the criteria for major
      depression (1.6% of the 551) and 6 fulfilled the criteria for minor depression
      (1.1%). Of the 9 that the IDD identified as suffering from major depression only
      one was diagnosed as such according to his medical chart. Two of the patients
      that the IDD found to be suffering from minor depression were diagnosed according
      to their medical chart as depressive. Five patients that were diagnosed by their
      physicians as suffering from depression were not diagnosed by the IDD. In a
      sample of patients who answered positively to one or more questions of the DIS,
      but refused to answer the IDD, it was found that 10 (20% of the sample) were
      diagnosed as depressed and 32% of the sample had some psychiatric diagnosis
      according to their charts. We discovered that patients who suffer from a
      depressive disorder visited their physicians more often than those that were not
      depressed: 12.7 and 7.14 respectively (during 6 months) (p < 0.028). IN SUMMARY:
      The combined two phase screening instrument was found to be impractical and
      problematic for use as a screening tool. There was a difference between the
      diagnoses that appeared in the charts and those resulting from the screening
      tool. Using the 3 questions from the DIS as a case finding tool for depression in
      high risk populations (such as frequent attenders) might prove useful in primary
      care setting.

PMID- 14702745
TI  - [Congenital cervical spondylolisthesis].
AB  - Cervical spondylolysis with spondylolisthesis is a complex abnormality involving
      the posterior elements of the cervical vertebra, and anterolisthesis of the same
      vertebra. Cervical spondylolysis is defined as a corticated cleft between the
      superior and inferior articular facets of the articular "pillar", the cervical
      equivalent of the pars intraarticularis in the lumbar spine. The typical
      radiological features of this condition are as follows: 1. Spondylolysis (a break
      in the "pillar" on one or both sides) 2. Spina bifida of dysplastic vertebra 3.
      Affection of posterior intervertebral joints (abnormal inclination of the
      superior and inferior articular facets of the affected bones may present)
      Recognition of this congenital disorder and its differentiation from traumatic
      injury is extremely important in patients who have a history of recent cervical
      trauma.

PMID- 14702746
TI  - [Knowledge and attitudes among women in the Arab village regarding contraception
      and family planning and the reasons for having numerous children].
AB  - BACKGROUND: Families with numerous children (5 or more) are a common phenomenon
      in the Arab sector in Israel. Whereas the fertility rate of Jewish women is 2.6,
      Muslim women have a rate of 4.6. Research has found that approximately half of
      the children were the result of unplanned pregnancies. Among the risk factors for
      unplanned pregnancies are: low income, the woman's level of education and
      marriage at a young age. In Israel a number of studies have been conducted on the
      use of contraception, in general, and on the status of women in the Arab
      population. However, to the best of our knowledge, there has not yet been a study
      in which Arab women have been asked how they customarily act on the subjects of
      family planning and contraception and what their attitudes are vis-a-vis having
      numerous children. OBJECTIVES: The aim of this study was to examine to what
      extent family planning and use of contraception exist in the Arab population and
      to determine the reasons for having so many children. The reasons examined
      included: the couple's wishes, religious faith, knowledge concerning
      contraception, socio-economic status and education. METHODS: A detailed
      questionnaire was prepared, which included socio-demographic details and
      questions of knowledge and attitudes pertaining to family planning and
      contraception and the reasons for having numerous children. The questionnaire was
      completed by the clinic staff, who interviewed all the women, ages 20-45, who had
      5 or more children. RESULTS: Three hundred and three Arab women were interviewed,
      out of a total of 391 who had 5 children or more (compliance rate of 77.5%).
      Sixty percent of these women were married before the age of 18 and most of them
      are housewives (96.4%). A total of 18.8% of the women had an education of 0-4
      years, 66.5% had an education of 5-8 years and 14.8% received 9 or more years of
      education. Most of them (92%) claimed that the decision regarding the number of
      children was jointly made with their husband; 24.8% thought that breastfeeding
      prevents pregnancy, about half of them became pregnant while breastfeeding. As to
      contraceptives--6.9% are currently taking contraceptive pills; 60.8% use IUD; and
      11.2% had tubal ligation, most of them during a Caesarian section. In a single
      variable analysis, a significant correlation was found between the women with a
      low level of education and more than 7 children. As the educational level rises
      there are fewer children in the family (P < 0.001). A significant correlation was
      also found between the low education of the husband and a number of children
      greater than 7 (P < 0.004). It was found that there is a significant high rate of
      women with 6 or more children that had tubal ligation. In a multi-variable
      analysis of the logistic regression, it was found that independent variables that
      predict a number of children higher than 7 are tubal ligation and the woman's
      level of education. The probability of uneducated women having 7 or more children
      is 15.2 times greater than for women with high education. Similarly, the
      probability that women who underwent tubal ligation have 7 or more children is
      5.8 times greater than women who used no contraception. CONCLUSIONS: This study
      reinforces findings from previous studies that indicate the connection between
      the parents' education, particularly the wife's education, and the number of
      children. Similarly, in the rural Arab sector in Israel, the woman's education is
      the most significant variable determining the number of children. Moreover, we
      have seen that only when the number of children is particularly high and the
      woman's age is high, she is persuaded to have tubal ligation, as opposed to other
      means of contraception. These results reinforce the approach, according to which
      there is great importance to the fact that women in the Arab sector should obtain
      a high school education and more, so as to be able to properly plan the size of
      their family.

PMID- 14702747
TI  - [Improvement of early detection of diabetic retinopathy--a primary care
      intervention study].
AB  - BACKGROUND: Annual screening for diabetic retinopathy is highly recommended. The
      early detection of background retinopathy and laser treatment can prevent most of
      the diabetes related blindness. However patient compliance is relatively low.
      AIM: We aimed to raise the performance of annual fundus examination among
      diabetic patients, and to evaluate the rate of undetected severe diabetic
      retinopathy. METHODS: The study took place in an urban primary care clinic
      located in an average socio-economic neighborhood. The intervention program was
      based on implementation by the clinic staff with no additional external
      resources. The program included: locating the diabetic population, extending
      telephone invitation, and establishing cooperation with ophthalmologists.
      RESULTS: In 2000, the year prior to the intervention, 42% (177/420) of our
      diabetic patients had a fundus examination. In 2001 the rate increased to 76%
      (318/420), an increase of 80%. In 17% (55/318) of the patients the ophthalmologic
      examination was positive, including 33 cases of background retinopathy. Patients
      with retinopathy had a significantly higher HbA1c levels and hypertension was
      more common. Twenty cases had an early diabetic retinopathy, while the other 13
      were immediately sent for laser treatment. In the laser treatment group, the male
      to female ratio was almost double (69% vs. 35%, p = 0.06). Diabetes duration was
      longer (15.6 + 4.9 years vs. 8.4 + 5.6, p < 0.001) and they had a significantly
      higher rate of diabetic foot and peripheral vascular disease. CONCLUSION: An
      intervention that involved primary care clinic staff without external resources
      increased compliance with annual fundus examination and detected diabetic
      retinopathy in a preventable stage.

PMID- 14702748
TI  - [Our experience with rehabilitation of patients with Pott's tuberculous
      paraplegia].
AB  - Spinal tuberculosis with paraplegia is rarely seen in Israel. All the 10 patients
      that were hospitalized in our rehabilitation departments had contracted the
      disease abroad prior to their immigration to Israel. The comprehensive
      rehabilitation process must include close cooperation between pulmonary
      physicians, orthopedic surgeons and rehabilitation medicine specialists. An
      updated review of the relevant literature is presented.

PMID- 14702749
TI  - [Apoptosis: death is part of life].
AB  - Kerr, Wyllie, and Currie who coined the term apoptosis (falling leaves in Greek)
      meant, among other features, to remark on the de-adhesiveness of apoptotic cells
      from their natural surroundings, following programmed cell death. Anoikis
      ("homeless" in Greek) is chronologically an inverse process: de-adhesiveness of
      viable cells from their surroundings inducing programmed cell death. Integrins
      are essential adhesive molecules in this process but additional factors probably
      play a role. Beyond the physiological importance, understanding these patterns
      will be relevant to maintain the vitality of cells used for cell therapy.
      Abnormal apoptosis and clearance of apoptotic cells is a fundamental factor in
      the pathogenesis of numerous diseases including cancer, neuro-degenerative and
      ischemic diseases, AIDS and autoimmunity. In systemic lupus erythematosus (SLE)
      the antigen responsible for most anti-DNA antibodies, exclusively generated in
      this disease, are derived from nucleosomes. As nucleosomes are mainly generated
      during programmed cell death, excess of apoptotic material and altered clearance
      may induce autoreactive immune responses. On the other side of the spectrum,
      failure to die, as exemplified in MRL/1pr mice and human lymphoproliferative
      disorder, may allow persistence of autoreactive cells and prevent the resolution
      of inflammation. When combined, we may conclude that dying properly is essential
      for living properly.

PMID- 14702750
TI  - [Vacuum--a novel method for treating chronic wounds].
AB  - Chronic wounds represent a major health burden and drain on resources. In spite
      of advances in our understanding of chronic wound biology and the development of
      new treatments, there is no one form of treatment suitable for all wounds and
      patients. Many factors can impair healing--local and systemic. The current
      treatments include different ways of debridement, occlusive hydrocolloid
      dressings, topical growth factors, hyperbaric oxygen, bioengineered skin
      equivalents and more. In the last decade there is an increment in the use of
      negative pressure dressing (VAC--vacuum assisted closure system) in the treatment
      of chronic wounds from different etiologies--diabetic, venous and pressure sores.
      Our experience demonstrated good results in the treatment of diabetic and venous
      insufficiency ulcers, and disappointing results in the treatment of pressure
      sores. Promising results were demonstrated in the treatment of acute injuries,
      lowering the need for microvascular reconstruction. Prospective researches
      examining the efficacy and cost effectiveness of this treatment in comparison to
      other methods are crucial for wise and extensive use of the VAC system.

PMID- 14702751
TI  - [Vacuum assisted closure--a new method for wound control and treatment].
AB  - Despite the numerous advances in wound healing research, the treatment of chronic
      non-healing wounds still presents a challenge. Vacuum assisted closure is a new
      technique for wound treatment using negative pressure. The method can be used for
      the treatment of a wide variety of wounds, including pressure sores, diabetic
      ulcers, venous ulcers, surgical traumatic wounds and radiated wounds. With the
      aid of this method pressure is distributed on the wound by using a foam with a
      specific pore size. The foam is placed over the wound and the wound is covered
      with an adherent, occlusive dressing thus converting the open wound to a
      controlled closed wound. The mechanism that stands for the positive effect of the
      negative pressure dressing is obtained by removing the third space fluids from
      the area immediately adjacent to the wounds, thus decreasing the pressure on
      small vessels and improving the blood supply to the wound with positive
      consequences for this increment. CONCLUSIONS AND RECOMMENDATIONS: A new method is
      presented for the treatment of chronic wounds using negative pressure. The
      application of the negative pressure to wounds can promote the healing of a
      variety of chronic non-healing wounds with significant increase in granulation
      tissue formation.

PMID- 14702752
TI  - [Longevity in gerontology and in Judaism--quantity years or quality years?].
AB  - In this day and age, we have been granted longevity--both a blessing and a curse.
      Longevity has resulted in new diseases, illnesses and long-term disabilities due
      to the shift from death caused by acute infectious diseases and by chronic
      diseases such as cancer, cardiac and vascular diseases, to morbidity caused by
      chronic cases of arthritis, Alzheimer's and sensory disabilities--auditory and
      visual. Chronic diseases are characterized by long-term illness and result in
      escalating reduction in functioning, with an increase in the elderly person's
      dependence on his family or society. What do we mean when we say 'longevity'? Do
      we add days to our lives or perhaps life to our days? What can we expect? How do
      we achieve longevity? I have looked into the Torah, into the words of the Sages
      and into the findings of geriatric research. I have found that, both in
      gerontology, and in the words of the Sages, longevity is accompanied by quality
      of life. In gerontology, 'quality of life' is measured as being active and
      independent, including the ability to carry out routine daily activities (ADL).
      Katz and his colleagues have used the terms 'active life expectancy' and
      'dependent life expectancy'. The ability to predict active life expectancy is no
      less important than predicting mortality, and particularly how to achieve active
      life expectancy. The Sages praise longevity, accompanied by wisdom: "In the
      elderly, wisdom, and in wisdom, long life' (Job). In addition, they say: 'For
      longevity and years of life and peace shall be granted to you' (Proverbs), to
      teach the blessing of longevity accompanied by wisdom. To achieve longevity, one
      should maintain regular habits that reduce the risk of illness such as physical
      exercise, a balanced diet, no smoking, and have a relaxed attitude to self
      importance and to financial matters, while emphasizing the routine and stable
      elements of one's daily life.

PMID- 14702753
TI  - [Apoptosis in systemic lupus erythematosus].
AB  - In autoimmune diseases including systemic lupus erythematosus (SLE), the immune
      system attacks various autoantigens and causes damage in target organs. Recently,
      it was found that dead cells serve as a repertoire for autoantigens which can
      stimulate an autoimmune response in sensitive persons. The mechanisms which lead
      to induction and progress of apoptosis include extra-cellular stimuli, intra
      cellular signals, and cleavage of proteins. During apoptosis, several events
      occur including migration of intra-cellular components to the cell membrane,
      removal of apoptotic cells by specific proteins and complement systems, and
      phagocytosis of apoptotic cells by macrophages. In recent years, evidence has
      accumulated that the autoimmune response can be initiated as a result of defects
      in apoptosis and/or removal of apoptotic material. In this article, the
      association of apoptosis to the pathogenesis of systemic lupus erythematosus is
      discussed.

PMID- 14702754
TI  - [The neurological manifestations of celiac disease in children].
AB  - Neurological manifestations are occasionally associated with celiac disease in
      both adults and children. In the past these manifestations were related to
      nutritional deficiencies. However, since neurological manifestations can be
      demonstrated in patients without nutritional deficiencies, the etiology may be
      immune or toxic mediated. We present an update on the neurological manifestations
      of celiac disease, particularly in children.

PMID- 14702755
TI  - [Osler-Weber-Rendu--a life-threatening disease in adults and children].
AB  - Osler-Weber-Rendu Syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is an
      autosomal dominant inherited disease. It is more common than previously
      estimated, with a prevalence of 1:5,000-10,000. It was described mainly in
      adults, however recent studies suggest a similar presentation in children. The
      clinical characteristics include epistaxis, skin and mucosal telangiectases and
      visceral arteriovenous malformations (AVMs), and diagnostic criteria for this
      disease have been established. Epistaxis and telangiectases appear in most
      patients. Epistaxis can be massive and difficult to treat. Pulmonary AVMs are
      present in 30% of patients and can result in right to left shunt, with dyspnea,
      cyanosis and polycythemia. The shunt, bypassing the pulmonary capillary bed, can
      also result in paradoxical emboli to the brain, strokes and brain abscesses.
      Different screening methods have been suggested for pulmonary AVMs, preferably
      high resolution chest CT and bubble echocardiography. Definite diagnosis is made
      by pulmonary angiography. The recommended treatment is pulmonary embolization and
      recent studies show excellent results in adults and children. Cerebral AVMs
      appear in 5% of patients and can result in cerebral hemorrhage. MRI is the
      recommended screening test. There is a debate as to whether to treat asymptomatic
      patients with cerebral AVMs. Mutations in two genes have been shown to cause 2
      types of this disease. Both genes encode proteins, endoglin and ALK-1, which are
      components of the TGF-beta receptor. Mutations in these genes cause HHT1 and
      HHT2, respectively. Screening family members of patients for pulmonary AVMs is
      recommended, and children should probably be included.

PMID- 14702756
TI  - [Anoikis--a specific form of programmed cell death].
AB  - Cell therapy, in particular liver cell transplantation, holds great therapeutic
      potential and is partially hindered by the high rate of apoptosis during cell
      isolation, cryopreservation and engraftment. Apoptosis triggered by cell
      detachment from the extracellular matrix, which occurs during hepatocyte
      isolation, is a phenomenon termed "anoikis". It's importance in the normal
      physiologic development of the human body, as well as in disease states, has been
      described. Cancer cells harbor anoikis resistance allowing spread to occur.
      Activation of the protein Fas associated death domain/MORT1 initiates the
      apoptosis cascade, with further downstream activation of caspase 8, Bid,
      cytochrome c and the executioner caspases. The anti-apoptotic protein family (bcl
      2) and integrins, in particular beta 1 integrin, balance the pro apoptotic
      signals. The family of caspase enzymes, currently including 14 members, is
      subdivided by the prodomain length, specific substrate and phylogenetic analysis,
      and plays a crucial role in the apoptotic cascade. Therefore, understanding the
      molecular biology of apoptosis and specifically the "form" termed anoikis, has
      advanced clinical implications in cancer and cell therapy research.

PMID- 14702758
TI  - [Geriatrics 2000].

PMID- 14702757
TI  - [Oral cancer--nuclear acid and genomic aberrations].
AB  - Squamous cell carcinoma of the oral cavity is the sixth most frequent cancer in
      the world and of the approximately 30,000 new cases diagnosed annually in the
      United States, 60% occur in males and over 90% of the cases occur in patients
      over 45 years of age. The overall 5-year survival rate for patients with oral
      squamous cell carcinoma is among the lowest for major cancers and has not changed
      during the past two decades. Assessing the risk of oral cancer prior to choosing
      the therapeutic strategy administered is of paramount importance. Although
      imperfect but generally available, assays that identify loss of heterozygosity
      and determine ploidy are an improvement over current ways of assessing the risk
      of oral cancer. Molecular probing significantly increases the sensitivity and
      specificity of conventional histopathology. It is now possible to detect a single
      cancer cell in 10,000 cells. In any case oral cancer remains a disfiguring
      disease associated with a high mortality rate. Abstinence from smoking and
      alcohol is the best approach to prevent its occurrence.

PMID- 14702759
TI  - [A rupture of aortic aneurysm].

PMID- 14702760
TI  - Law enhances hygienists' duties, frees dentists for complex cases.

PMID- 14702761
TI  - Tuberculosis.
AB  - Tuberculosis, a chronic bacterial infection, once thought to have been
      eliminated, has re-emerged as a disease threat, causing health care professionals
      to evaluate the treatment of those infected. This article provides information on
      the transmission of the disease, infection and active disease, and
      recommendations for evaluating patients in the dental setting.

PMID- 14702762
TI  - Regional odontodysplasia. A case report.
AB  - Regional odontodysplasia (RO) is an unusual, non-hereditary anomaly of the dental
      hard tissues with characteristic clinical, radiographic and histological
      findings. Etiology is unknown, and treatment, while varied, should be appropriate
      for each individual's clinical findings. In the case reported here, a 2-year-old
      female was diagnosed with RO. Extractions were performed under general
      anesthesia. Clinical, radiographic, and histological findings are described.

PMID- 14702763
TI  - An oral surgeon's evaluation of Emdogain.
AB  - A product developed by researchers in Sweden (Biora AB Malmo, Sweden) has been
      approved by the United States Food and Drug Administration for use in the
      regeneration of periodontal attachment apparatus. Enamel matrix protein
      (Emdogain) has been shown to be effective in animal and human studies. This
      report documents a series of 19 clinical trials to help retain "hopeless" teeth
      referred for extraction. It was offered as an alternative to extraction. The
      techniques used involved a departure from the method specifically recommended by
      the manufacturer. Seventeen of the 19 teeth treated showed significant
      improvement with decreased mobility, improved attachment levels and new bone on
      follow-up radiographic examination.

PMID- 14702764
TI  - A Victorian physician ahead of his time. The story of fluorine advocate Sir James
      Crichton-Browne.
AB  - Sir James Crichton-Browne, one of England's most renowned psychiatrists, whose
      career spanned two centuries, had very strong feelings about the need to secure
      proper dental care for all the children of his country. He translated these
      feelings into action when he advocated that fluorine be added to the diets of
      pregnant women and children. And this was almost a half-century before definitive
      research showed the value of fluorine as a preventive of caries.

PMID- 14702765
TI  - Descriptive epidemiology of limb reduction deformities in Hawaii, 1986-2000.
AB  - The relationship between limb reduction deformities and clinical and demographic
      factors in Hawaii during 1986-2000 were examined using population-based birth
      defects program data. The limb defect rate was highest with maternal age less
      than 20 years, and the defect was more common among males. Among racial/ethnic
      groups, Pacific Islanders and Filipinos had higher rates than whites and Far East
      Asians.

PMID- 14702766
TI  - Spontaneous coronary artery dissection in a patient with systemic lupus
      erythematosis.
AB  - Spontaneous coronary artery dissection (SCAD) is an uncommon condition that may
      lead to sudden coronary artery occlusion resulting in a fatal acute myocardial
      infarction. It usually affects young to middle age women. A Medline search from
      1966 to 2001 (using keywords: coronary artery dissection and systemic lupus
      erythematosis) revealed no prior reports of coronary dissection in a patient with
      systemic lupus erythematosis (SLE). We describe a 48-year old woman with SLE who
      sustained a fatal spontaneous left main coronary artery dissection. Coronary
      angiogram was notable for marked variability in the size of coronary lumen from
      systole to diastole. This case demonstrates the need to consider SCAD in the
      evaluation of chest pain and myocardial infarction in patients with SLE.
      Furthermore, in the absence of classical angiographic findings of coronary
      dissection, a detailed review of phasic changes in coronary lumen during a
      cardiac cycle could help reach this diagnosis.

PMID- 14702767
TI  - The role of program evaluation in medical education at the John A. Burns School
      of Medicine.
AB  - An effective program evaluation process is vital to the management of a medical
      school curriculum. JABSOM's comprehensive program evaluation system helps to
      ensure that the school remains a leader in medical education and provides
      valuable information in its quest to develop outstanding physicians who will
      serve the people of Hawaii and the Pacific.

PMID- 14702769
TI  - HFMA forums. Real-world connections, ideas, and solutions.

PMID- 14702768
TI  - Risk associated with obesity and its related lifestyle factors: what about
      cancer?

PMID- 14702770
TI  - New project provides information, tools to enhance capital access.

PMID- 14702771
TI  - Perspectives on the revenue cycle. Insights and resources for revenue-cycle
      leaders.

PMID- 14702772
TI  - Are you paying your PA staff what they deserve?

PMID- 14702773
TI  - Implementing a proactive rejection strategy.

PMID- 14702774
TI  - Recognizing the human element in the revenue cycle.

PMID- 14702775
TI  - Capitalizing on HIPAA.

PMID- 14702776
TI  - Holding payers accountable for payment practices.

PMID- 14702777
TI  - Assess your personal performance with key performance measures.

PMID- 14702778
TI  - Training in breast reconstruction: a new chapter in breast surgery.

PMID- 14702779
TI  - Developments in understanding and management of inflammatory bowel disease.

PMID- 14702780
TI  - Medical management of ulcerative colitis.
AB  - Patients with ulcerative colitis have no increased mortality compared to
      population controls and the disease can be cured be colectomy. This review
      concentrates on the medical management of ulcerative colitis including the
      management of active colitis, acute severe colitis and first presentation of
      colitis, maintenance of remission and long-term complications.

PMID- 14702781
TI  - Biological therapy in Crohn's disease.
AB  - The discovery of the central role of tumour necrosis factor-alpha in Crohn's
      disease and the subsequent introduction of infliximab into routine clinical
      practice has transformed the treatment of refractory disease. Advances in
      understanding of the immunopathological basis of Crohn's disease are leading to
      the development of new biological therapies which are likely to play an
      increasing role in future.

PMID- 14702782
TI  - Medical management of Crohn's disease.
AB  - Current evidence strongly suggests that Crohn's disease is caused by an abnormal
      response to enteric flora. This review examines the current evidence for medical
      management of Crohn's disease, particularly focusing on alternative therapies to
      corticosteroids in managing disease relapses and preventing long-term
      complications.

PMID- 14702783
TI  - Surgery for inflammatory bowel disease.
AB  - Ulcerative colitis is potentially cured by total excision of the colon and
      rectum. Crohn's disease is an unremitting condition in which operations are
      frequently multiple and in which the minimum amount of bowel possible should be
      excised.

PMID- 14702784
TI  - Laparoscopic surgery for inflammatory bowel disease.
AB  - Laparoscopic surgery for inflammatory bowel disease is an expanding field, which
      has physical benefits to the patient and economic benefits to the trust and
      community.

PMID- 14702785
TI  - Preventing and managing aggression and violence in the NHS.
AB  - Streaming in emergency departments reduces waiting times and stress, and removes
      the causes of most violent attacks against staff. In spite of this some people
      will still attack staff. Staff must be protected by a sound trust policy and
      effective and realistic training, monitored by a good reporting system.

PMID- 14702786
TI  - Where do we stand with chronic prostatitis? An update.
AB  - Chronic prostatitis remains a difficult management problem, which reflects the
      fact that its aetiology remains incompletely understood. It is a common condition
      that is characterized by protracted symptoms and high morbidity. Although lacking
      a reliable diagnostic test, antibiotic therapy remains the mainstay of treatment
      in the majority of cases.

PMID- 14702787
TI  - Radiofrequency ablation of unresectable liver tumours.
AB  - Unresectable liver tumours have a dismal prognosis. Treatment with systemic or
      regional chemotherapy rarely results in a durable complete response.
      Radiofrequency ablation is a novel technique to achieve local destruction, which
      can be repeated and has been shown to be safe and effective.

PMID- 14702788
TI  - Factors influencing teaching and learning in the preregistration year.
AB  - Preregistration training is a transitional period in the career of new medical
      graduates as they complete their final year of basic medical education in
      practice settings. This study gathered the views of both preregistration house
      officers and their educational supervisors on preregistration training in the
      Mersey Deanery between August 2000 and August 2001.

PMID- 14702789
TI  - Parasites and the eye.

PMID- 14702790
TI  - Mistaken identity: calcific tendinitis in the finger.

PMID- 14702791
TI  - A rare presentation of caecal adenocarcinoma.

PMID- 14702792
TI  - In the public's view... vomiting on the high seas.

PMID- 14702793
TI  - A pain in the neck: dissection of the vertebral artery.

PMID- 14702794
TI  - Cardiopulmonary resuscitation: junior doctors' attitudes.

PMID- 14702795
TI  - Non-steroidal anti-inflammatory drugs and the asthmatic child.

PMID- 14702796
TI  - [What is the best way to screen for Down syndrome?].

PMID- 14702797
TI  - [What new about hypertrophic cardiomyopathy?].

PMID- 14702798
TI  - [Psychological advantages and disadvantages of mammography screenings].

PMID- 14702799
TI  - [Black arrhythmias?].

PMID- 14702800
TI  - [An odd creature in the toilet bowl].

PMID- 14702801
TI  - [Interactions of herbal products and drugs].

PMID- 14702802
TI  - [On pheochromocytoma that was treated as a panic disorder].

PMID- 14702803
TI  - [Safe use of anti-inflammatory analgesics].

PMID- 14702804
TI  - [Louis Lagrenee Sr.: Pygmalion and his sculptures].

PMID- 14702805
TI  - [Estrogen therapies--where are we now?].

PMID- 14702806
TI  - [Multiple faces of the actions of estrogen].

PMID- 14702807
TI  - [Bones are breaking without estrogen].

PMID- 14702808
TI  - [Estrogen and cardiovascular diseases].

PMID- 14702809
TI  - [Is estrogen replacement therapy increasing or decreasing the risk of cancer?].

PMID- 14702810
TI  - [Neuropause?].

PMID- 14702811
TI  - [Quality of life from estrogen].

PMID- 14702812
TI  - [How will I treat my patient using estrogen?].

PMID- 14702813
TI  - [Psychiatric emergencies in the homeless: refusal to hospitalize only for
      humanitarian reasons].

PMID- 14702814
TI  - [What do "p" and confidence interval mean?].

PMID- 14702815
TI  - [Treatment of rheumatoid polyarthritis. The revolution of biotherapies].

PMID- 14702816
TI  - [Urinary tract infections. What has changed].

PMID- 14702817
TI  - [Bacteriologic diagnosis and antibiotic therapy of urinary tract infections].
AB  - The laboratory diagnosis and antibiotic treatment of urinary tract infections
      (UTIs) are very different depending on the clinical context. It is critical to
      distinguish between uncomplicated infections and infections complicated by
      abnormalities of the urinary tract or other host factors. Microscopic examination
      combined with urine culture remains the test of reference, excepted for
      uncomplicated cystitis. It requires rigorous method and analysis taking into
      account of clinical data. For empirical therapy, the choice is well codified in
      case of community acquired UTIs since the bacterial species involved are very
      stable over time and space, and since their antibiotic resistances are well known
      (with currently a high prevalence of resistance not only to aminopenicillins but
      also to amoxicillin-clavulanate and trimethoprim-sulfamethoxazole); in contrast,
      the treatment of nosocomial UTIs is difficult because of the diversity of
      causative organisms and of antibiotic resistance profiles.

PMID- 14702818
TI  - [Bacteriologic mechanisms of infections of the urinary tract].

PMID- 14702819
TI  - [Cystitis].
AB  - Bacterial cystitis is a common condition characterised by a high incidence, an
      easy diagnosis and a simple treatment. Three subsets should be distinguished:
      simple cystitis, occurring in young women, requires no bacteriologic work-up and
      is best treated by a single dose or a three-day regimen consisting of a common
      antibiotic, complicated cystitis, occurring in patients with diabetes, an
      urologic history or immunosuppression; it requires a seven-day treatment course,
      the choice of which is guided by antibiotic sensitivity tests; recurrent cystitis
      is defined by, at least, four yearly flares; such recurrences warrant thorough
      vulvo-vaginal examination seeking a local lesion; if none is found, protracted
      treatment using an inhibitory rather than a bactericidal antibiotic dosage is an
      efficient prophylactic regimen.

PMID- 14702820
TI  - [Acute pyelonephritis].
AB  - Acute pyelonephritis is frequent. Its usual signs and symptoms comprise renal
      pain, fever, inflammation, and pyuria. Simple acute E. coli pyelonephritis is
      frequent in the young female and in most cases is a benign condition. A typical
      pyelonephritis may be painless, or without high fever, or lacking bacterial
      growth in the urine due to previous inappropriate treatment. Severe, complicated
      pyelonephritis is mainly observed in diabetic, alcoholic or immunocompromised
      patients. In occasional cases, a common form of pyelonephritis may progress to
      formation of a renal abscess requiring drainage. When secondary to urinary tract
      abnormalities, pyelonephritis may be complicated with septicemia and can induce
      early and severe renal tissue damage. This form warrants emergency urologic
      treatment. Simple pyelonephritis of the young female without febrile UTI history
      requires little imaging. Conversely, extensive imaging workup is mandatory in the
      male, the elderly, when treatment is not rapidly effective or in case of early
      relapse. In some cases, acute pyelonephritis leads to the development of cortical
      scars, the long-term prognosis of which remains to be determined.

PMID- 14702821
TI  - [Prostatitis].
AB  - A very frequent disease, prostatitis is always infectious in the acute form and
      rarely so in the chronic form (less than 10%). The management of acute
      prostatitis requires simplicity and efficiency. Fluoroquinolones taken for 3
      weeks are the treatment of reference. The identification of chronic prostatitis
      requires the Meares and Stamey test, and the use of the 1995 NIH classification.
      Antibiotic treatment when indicated (confirmed or suspected infectious forms) has
      to be very prolonged (4 to 6 weeks). There are neither tests nor diagnostic
      markers for the non-infectious forms (chronic pelvic pain syndrome). From this
      fact, diagnostic explorations and the eventual treatments vary greatly and are
      currently not codified.

PMID- 14702822
TI  - [Urinary tract infections and diabetes mellitus].
AB  - The prevalence of urinary tract infection (UTI) is high in patients with diabetes
      mellitus. They run a distinctly greater risk of complications than non-diabetics.
      Systematic antibiotic treatment is mandatory. Screening of UTI must be carried
      out in diabetics at least annually, and be considered when the metabolic control
      of diabetes becomes increasingly difficult without another clear explanation.
      Complicated forms are common. They comprise severe pyelonephritis and renal
      abscesses, emphysematous pyellitis and pyelonephritis, renal papillary necrosis
      and sepsis. Nosocomial UTI is frequent in such patients. Meticulous preventive
      measures are the best means of reducing the prevalence of UTI in diabetics.

PMID- 14702823
TI  - [Urinary tract infections in pregnancy].
AB  - Lower urinary tract infections (UTI) more readily evolve towards acute
      pyelonephritis (AP) during pregnancy. It should thus be considered as a serious
      situation. UTI screening is not routinely achieved but appears advisable because
      the treatment notably reduces the occurrence AP. The effectiveness of urinary
      testing by dipstick is good even though it can't compete with the sensitivity and
      specificity of urine culture. AP mainly increases the risk of prematurity. Prompt
      therapy should be carried out since renal function could be compromised by
      parenchymal infection. Unfavourable outcome mainly occurs in complicated UTI that
      it may reveal but that can often be drawn out form the patient's medical history.

PMID- 14702824
TI  - [Urinary tract infections in MEDLINE].

PMID- 14702825
TI  - [Patient card. Cystitis: 10 tips to prevent recurrences].

PMID- 14702826
TI  - [Atrial fibrillation].

PMID- 14702827
TI  - [Prescription of a thermal spa].

PMID- 14702828
TI  - [Social protection. Update complement].

PMID- 14702829
TI  - [Antalgic, pharmacologic and non-pharmacologic treatments].

PMID- 14702830
TI  - [Strabismus in children].

PMID- 14702831
TI  - [Behavior disorders in adolescence].

PMID- 14702832
TI  - [The main ethical principles in the 20th century (I). The slow birth of a
      confidential ethics].

PMID- 14702833
TI  - Mycetoma: a thorn in the flesh.
AB  - Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory disease caused
      by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). It occurs in
      the mycetoma belt stretching between the latitudes of 15 degrees South and 30
      degrees North and is endemic in relatively arid areas. The organisms are present
      in the soil and may enter the subcutaneous tissue by traumatic inoculation.
      Mycetoma commonly affects adults aged 20 to 40 years, predominantly males. The
      foot is most commonly affected. Both forms of mycetoma present as a progressive,
      subcutaneous swelling, although actinomycetoma has a more rapid course. Multiple
      nodules develop which may suppurate and drain through sinuses, discharging grains
      during the active phase of the disease. Diagnosis may involve radiology,
      ultrasonic imaging, cytology, culture, histology or immunodiagnosis.
      Actinomycetoma is amenable to treatment by antibiotics, preferably by combined
      drug therapy for long periods. Eumycetoma is usually treated by aggressive
      surgical excision combined with medical treatment.

PMID- 14702834
TI  - PCR as a rapid and sensitive tool in the diagnosis of human and canine
      leishmaniasis using Leishmania donovani s.l.-specific kinetoplastid primers.
AB  - This study was performed in order to test the efficacy of a new polymerase chain
      reaction (PCR) assay for the diagnosis of both human and canine leishmaniasis
      caused by Leishmania infantum. The new primers were developed on the basis of a
      complete DNA sequence of the L. infantum kinetoplast minicircle. Specificity and
      sensitivity were evaluated by testing bone marrow spots on filter paper and skin
      biopsy samples, and the PCR results were compared to data from in vitro cultures.
      Leishmania strains from different foci, as well as other trypanosomatids and
      opportunistic pathogenic micro-organisms, were also included in this study. The
      results show that the primers are highly specific, detecting only L. donovani
      s.l. DNA, and sensitive for the detection of parasite DNA in biological samples
      from three different geographical regions of Portugal (north, centre and south)
      and from Brazil.

PMID- 14702835
TI  - Efficacy and side effects of praziquantel against Schistosoma mansoni in a
      community of western Cote d'Ivoire.
AB  - Praziquantel is efficacious against the adult stages of all human schistosome
      parasites, and has become the drug of choice for morbidity control of
      schistosomiasis. There is concern that resistance to praziquantel might develop
      or already exists, and could be further facilitated through new control
      initiatives relying on large-scale administration of praziquantel. Therefore,
      monitoring praziquantel efficacy in different epidemiological settings is
      required. We assessed the efficacy and side effects of praziquantel against
      Schistosoma mansoni in a rural community of western Cote d'Ivoire. Three
      consecutive stool specimens from 545 children and adults were examined by the
      Kato-Katz technique, revealing an overall prevalence of 40.9%. S. mansoni
      infected individuals were treated with a single oral dose of praziquantel at 40
      mg/kg. The most frequent side effects were abdominal pain, dizziness and
      diarrhoea. The overall cure rate, assessed 6 weeks post-treatment, was 60.9%.
      Moderate or heavy infections were only cleared in half or one-third of the
      individuals, respectively. The total egg count reduction was 61.4%. Infection
      intensity pre-treatment was significantly associated with age, cure rate,
      reported diarrhoea and dizziness. Our findings call for additional studies that
      rigorously evaluate the efficacy of praziquantel against different schistosome
      species in entire communities, using similarly sensitive diagnostic approaches as
      employed here.

PMID- 14702836
TI  - Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites
      in the north eastern Amazon region of Brazil.
AB  - The efficacies of specific Bothrops atrox-Lachesis and standard Bothrops-Lachesis
      antivenoms were compared in the north eastern Amazon region of Brazil. The main
      aim was to investigate whether a specific antivenom raised against the venom of
      B. atrox, the most important Amazon snake species from a medical point of view,
      was necessary for the treatment of patients in this region. Seventy-four patients
      with local and systemic effects of envenoming by Bothrops or Lachesis snakes were
      randomly allocated to receive either specific (n = 38) or standard (n = 36)
      antivenoms. In 46 cases (24 in the standard antivenom group, 22 in the other) the
      snake was identified either by enzyme immunoassay or by examination of the dead
      snake, as B. atrox in 45, L. muta in one. Patients were similar in all clinical
      and epidemiological respects before treatment. Results indicated that both
      antivenoms were equally effective in reversing all signs of envenoming detected
      both clinically and in the laboratory. Venom-induced haemostatic abnormalities
      were resolved within 24 h after the start of antivenom therapy in most patients.
      The extent of local complications, such as local skin necrosis and secondary
      infection, was similar in both groups. There were no deaths. The incidence of
      early anaphylactic reactions was 18% and 19%, respectively for specific and
      standard antivenoms; none was life-threatening. Measurement of serum venom
      concentrations by enzyme immunoassay (EIA) confirmed that both antivenoms cleared
      venom antigenaemia effectively. EIA also revealed that one patient had been
      bitten by Lachesis muta, although the clinical features in this case were not
      distinctive.

PMID- 14702837
TI  - Aedes aegypti in Brazil: genetically differentiated populations with high
      susceptibility to dengue and yellow fever viruses.
AB  - Aedes aegypti was eliminated from Brazil in 1955, but re-infested the country in
      the 1970s. Dengue outbreaks have occurred since 1981 and became endemic in
      several cities in Brazil after 1986. Urban yellow fever has not occurred since
      1942, and only jungle yellow fever cases have been reported. A population genetic
      analysis using isoenzyme variation combined with an evaluation of susceptibility
      to both yellow fever and dengue 2 viruses was conducted among 23 A. aegypti
      samples from 13 Brazilian states. We demonstrated that experimental infection
      rates of A. aegypti for both dengue and yellow fever viruses (YFV) are high and
      heterogeneous, and samples collected in the endemic and transition areas of
      sylvatic yellow fever were highly susceptible to yellow fever virus. Boa Vista, a
      border city between Brazil and Venezuela, and Rio de Janeiro in the Southeast
      region are considered as the most important entry points for dengue
      dissemination. Considering the high densities of A. aegypti, and its high
      susceptibility to dengue and yellow fever viruses, the risk of dengue epidemics
      and yellow fever urbanization in Brazil is more real than ever.

PMID- 14702838
TI  - Risk factors for malaria in UK travellers.
AB  - After observing an apparent increase in severe falciparum malaria among
      travellers returning from The Gambia to the United Kingdom (UK) in the last
      quarter of 2000, we conducted a case-control study to investigate risk factors
      for malaria. The study participants had visited The Gambia between 1 September
      and 31 December 2000, travelling with the largest UK tour operator serving this
      destination. The main outcome measures were risk factors associated with malaria.
      Forty-six cases and 557 controls were studied. Eighty-seven percent of all
      participants reported antimalarial use (41% chloroquine/proguanil, 31%
      mefloquine). On univariate analysis the strongest risk factors for disease were:
      early calendar period of visit, longer duration of stay, non-use of antimalarial
      prophylaxis, non-use of mefloquine, lack of room air-conditioning, less use of
      insect repellent, prior visit to another malarial area and accommodation in
      'hotel X'. After adjustment in multivariate analysis, use of mefloquine remained
      strongly protective (odds ratios, OR 0.13 [95% confidence intervals, 95% CI 0.04
      0.40]), and the strongest independent risk factors for malaria were early
      calendar period (OR 5.19 [2.35-11.45] for 1 September to 9 November 2000 versus
      10 November to 31 December 2000), prior visit to another malarial area (OR 3.27
      [1.41-7.56]), main accommodation in 'hotel X' (OR 3.24 [1.51-6.97]) and duration
      of stay (OR 2.05 per extra week [1.42-2.95]). Neither any use, nor > 90%
      adherence to chloroquine/proguanil were protective (adjusted OR for any use 0.57
      [0.27-1.21], P = 0.14). We concluded mefloquine use was strongly protective
      against malaria (87% protective efficacy), whereas chloroquine/proguanil, which
      is no longer recommended but remains widely used, was less than half as effective
      (43% protective efficacy). Waning efficacy of chloroquine/proguanil may have
      contributed to the observed increase in malaria among travellers to The Gambia in
      2000. Local factors may also influence the risk of malaria. Malaria could be
      prevented among travellers to West Africa if current national guidelines on
      antimalarial prophylaxis were better implemented.

PMID- 14702839
TI  - The isolation of Leishmania tropica and L. aethiopica from Phlebotomus
      (Paraphlebotomus) species (Diptera: Psychodidae) in the Awash Valley,
      northeastern Ethiopia.
AB  - In a survey of Leishmania infections in phlebotomine sandflies in a highly
      suspected focus of leishmaniasis in the Awash Valley (northeastern Ethiopia)
      between January 1994 and August 1997, a total of 3307 females of 11 Phlebotomus
      species (P. orientalis, P. fantalensis, P. saevus, P. sergenti, P. gemetchi, P.
      alexandri, P. bergeroti, P. duboscqi, P. arabicus, P. martini, and P. rodhaini)
      were dissected. Promastigotes were detected in 17 females of three species (11 P.
      saevus, 4 P. sergenti and 2 P. arabicus). Of these, only two P. saevus (one from
      Upper Awash and one from Middle Awash) and three P. sergenti (from Upper Awash)
      positives were successfully isolated in culture and were typed by isoenzyme
      analysis. Four isolates (two each from P. saevus and P. sergenti) were identified
      as new zymodemes (Z) of L. tropica and one isolate from P. sergenti was typed as
      a new zymodeme of L. aethiopica. This is the first finding of natural infections
      of P. saevus and P. arabicus and the first evidence for the former to be a vector
      of L. tropica. This is also the first time P. sergenti has been implicated in L.
      tropica transmission in Ethiopia; the isolation of L. aethiopica from a
      Paraphlebotomus species (P. sergenti) is also a new record. The possible presence
      of human cutaneous leishmaniasis (L. tropica and L. aethiopica), and wild
      reservoir host(s) of the parasites, especially rock hyrax (Procavia capensis) in
      the Upper and Middle Awash Valley remain to be determined.

PMID- 14702840
TI  - Rabies, lassaviruses and bats.

PMID- 14702841
TI  - Landfill sites: is the risk of adverse birth outcomes really different in
      Scotland?

PMID- 14702842
TI  - No excess risk of adverse birth outcomes in populations living near special waste
      landfill sites in Scotland.
AB  - A recent study showed small excess risks of low birth weight, very low birth
      weight and certain congenital anomalies in populations living near landfill sites
      in Great Britain. The objective of the current study was to investigate the risk
      of adverse birth outcomes associated with residence near special waste landfill
      sites in Scotland. We studied risks of adverse birth outcomes in populations
      living within 2 km of 61 Scottish special waste landfill sites operational at
      some time between 1982 and 1997 compared with those living further away. 324,167
      live births, 1,849 stillbirths, and 11,138 congenital anomalies (including
      terminations) were included in the study. Relative risks were computed for all
      congenital anomalies combined, some specific anomalies and prevalence of
      stillbirth and low and very low birth weight (< 2500 g and < 1500 g). For all
      anomalies combined, relative risk of residence near special waste landfill sites
      was 0.96 (99% confidence interval 0.89 to 1.02) adjusted for confounders.
      Adjusted risks were 0.71 (0.36 to 1.42) for neural tube defects, 1.03 (0.85 to
      1.26) for cardiovascular defects, 0.84 (0.58 to 1.22) for hypospadias and
      epispadias (with no excess of surgical corrections), 0.78 (0.27 to 2.23) for
      abdominal wall defects (1.32 (0.42-4.17) for hospital admissions), 1.22 (0.28 to
      5.38) for surgical correction of gastroschisis and exomphalos and 1.01 (0.96 to
      1.07) and 1.01 (0.90 to 1.15) for low and very low birth weight respectively.
      There was no excess risk of stillbirth. In conclusion, we found no statistically
      significant excess risks of congenital anomalies or low birth weight in
      populations living near special waste landfill sites in Scotland.

PMID- 14702843
TI  - Respiratory syncytial virus bronchiolitis in ex-preterm infants in the Scottish
      highlands: review of hospital admissions and an analysis of hospital cost.
AB  - Ex-preterm infants are vulnerable to respiratory syncytial virus (RSV)
      bronchiolitis and their hospital admission is associated with increased
      morbidity. Palivizumab is currently available as prophylaxis against RSV
      infection but its use in ex-preterm infants is controversial. A retrospective
      case review study was, therefore, carried out to determine the rate of
      readmission with RSV bronchiolitis among ex-preterm infants in the Highland
      Region of Scotland and to estimate the hospital cost per admission. Between 1995
      and 1999, a total of 3,046 children under 2 years of age were admitted to
      Raigmore Hospital, 1,691 of whom (60.4%) lived outwith Inverness. 507 children
      had acute bronchiolitis and ex preterm infants with RSV positive bronchiolitis
      accounted for 3.6% of total admissions with acute bronchiolitis. 72% of these
      children lived outwith Inverness. The median length of hospital stay for children
      born at less than 30 weeks and for children who had had bronchopulmonary
      dysplasia (BPD) was 6 and 10.5 days respectively. The average hospital costs per
      admission for children of less than 30 weeks and children of more than 30 weeks
      were 3,376 Pounds and 2,074 Pounds respectively. It was more expensive for
      children with BPD (4,431 Pounds per admission) when compared with those without
      BPD (1,959 Pounds per admission). This study has shown that most of the children
      admitted to hospital lived outwith Inverness, many at some considerable distance,
      and this, as much as severity of illness, may have contributed to hospital
      admission. Further studies are required to determine productivity losses
      associated with RSV infection and justification of use of Palivizumab in ex
      preterm infants of less than 30 weeks gestation and of BPD living in remote areas
      of Scottish Highlands.

PMID- 14702844
TI  - Drug-related deaths in Grampian, Scotland.
AB  - AIMS: To analyse the demographic data from fatalities arising directly from
      illicit drug abuse in the Grampian area and compare the findings with trends in
      drug seizures in Grampian to ascertain if these reflect the recorded deaths, and
      to attempt to identify a subgroup of the abusing population which might be at
      greater danger from overdose of controlled substances. METHODS: Cases in which
      the cause of death was directly attributed to illicit drugs from the beginning of
      January 1995 until the end of December 1999 were identified, and their
      epidemiological and toxicological data were analysed. The information regarding
      drug seizures was gained from Home Office publications for the same time period.
      RESULTS: One hundred and thirteen cases were retrieved consisting of 93 males and
      20 females, aged 16 to 43 years (Median 25). The most commonly isolated substance
      was morphine followed by benzodiazepines. In 97 cases two or more drugs were
      involved with five cases showing positive toxicology for four or more drugs. Of
      the female deaths 75% fell into the 16-25 year age range. Drug seizures rose by
      49% from 1995 to 1998 with both heroin and benzodiazepine seizures increasing by
      more than five fold in the same period. CONCLUSIONS: Deaths directly due to
      illicit drugs showed a significant increase over the study period and were
      concentrated in the young male population. The drug seizures increased but the
      extent of this was not mirrored in the deaths. A shift in emphasis to an older
      age group is also indicated; drug misuse educational programmes should continue
      to be targeted at all populations but information may also be targeted at the
      older age groups and at females under 25 years of age.

PMID- 14702845
TI  - Analysis of alcohol-related admissions in gastroenterology, cardiology and
      respiratory medicine.
AB  - A 4 week study of medical inpatients was performed to look at prevalence of
      alcohol-related problems in three different sub-specialties. Alcohol-related
      conditions accounted for 51% of gastroenterology inpatients, and 65% of these
      patients had alcoholic liver disease. In contrast, the cardiologists and
      respiratory physicians managed for less alcohol-related pathology, accounting for
      only 6% of inpatients in each specialty. Alcohol-related conditions were three
      times commoner in men. Patients admitted due to alcohol had longer lengths of
      stay, and experienced higher morbidity and mortality. These findings have
      important implications for health care planning and provision. They highlight a
      need for specialist training to be given to staff who deal with alcohol-related
      conditions on a daily basis. There is also a significant public health issue
      raised by these results regarding public attitudes in Scotland towards alcohol
      abuse and the increasing burden it is placing on the NHS.

PMID- 14702846
TI  - Epidemiology of permanent childhood hearing loss in Glasgow, 1985-1994.
AB  - This retrospective study was undertaken to document the epidemiology of permanent
      childhood hearing impairment (PCHI) in Glasgow and to make some assessment of the
      current practice to identify these children before universal neonatal hearing
      screening (UNHS) is implemented. Subjects were those with bilateral permanent
      hearing impairments of at least 40 dB in the better hearing ear, born between
      1985 and 1994, in Greater Glasgow. The subjects were identified and data
      extracted from the Educational Audiology database. The case records at the Royal
      Hospital for Sick Children were also reviewed to identify possible aetiology
      groups. The prevalence rate of all permanent hearing impairments was 1.23 per
      thousand live births. Eleven percent of all hearing impairments were acquired or
      progressive. There was no significant effect of sex on aetiology (X2 = 6.509, df
      = 6, p, = 1), age at identification of hearing impairment and hearing aid
      provision (Kruskal Wallis, p = 0.484 and 0.782 respectively). For those
      identified as congenitally hearing impaired, the median ages at diagnosis of
      hearing impairment and hearing aid provision were 18 months and 31 months
      respectively. Age at diagnosis of hearing impairment and hearing aid provision
      were unaffected by aetiology of hearing impairment (Kruskal Wallis, p = 0.782 and
      p = 0.484 respectively). The prevalence rate of PCHI and the ages at
      identification and intervention in Glasgow are typical of the rest of the UK.
      Audiological surveillance measures are falling well below the standard of care
      expected today and the introduction of UNHS is likely to improve outcomes as long
      as the additional health and educational resources are in place to deal with the
      earlier identification of these children.

PMID- 14702847
TI  - Do we practise what we preach?
AB  - There are recommendations regarding many facets of lifestyle. We proposed to look
      at hospital doctors' habits in East Yorkshire. METHOD: A simple questionnaire was
      sent out to 574 doctors in the Hull and East Yorkshire Hospitals NHS Trust. Non
      responders were re-mailed. Age, sex, grade, specialty, number of portions of
      fruit and vegetable per day, alcohol intake, smoking, exercise and hours worked.
      RESULTS: 301 doctors (238 males, 60 females) responded (response rate 58%).
      Approximately half of doctors who responded were consultants. Few respondents
      smoked (6.6%), and the mean alcohol consumption, 8.35 units per week (SE 0.54),
      was less than the recommended limits for men and women. Most doctors fell short
      of the "recommended" 5 portions of fruit and vegetables per day (median 3 per
      day) and nearly half worked more than 56 hours per week. Most respondents took at
      least the recommended amount of exercise per week (112 SE25 minutes) although 26%
      of doctors took no exercise at all.

PMID- 14702848
TI  - A case report of acute gastric volvulus with avulsion of the splenic vessels.
AB  - Gastric volvulus is a rare condition which usually presents with intermittent
      abdominal pain. It is typically associated with a paraoesophageal hiatus hernia
      and may present with acute strangulation or perforation. The mortality associated
      with an acutely obstructed volvulus may be up to 50%. Correspondingly, this
      condition is regarded as a surgical emergency. We present the history of a
      patient with an acute gastric volvulus and unexplained hypotension.

PMID- 14702849
TI  - Time to finally abandon a false trail. All surgical roads lead to John Hunter.

PMID- 14702850
TI  - Year of living dangerously.

PMID- 14702851
TI  - Taken short.

PMID- 14702852
TI  - Clinical management. Where medicine meets management. Under the influence.
AB  - The cost of alcohol-related illness could be as high as 3 Pounds bn a year.
      Charities are pushing for the inclusion of alcohol intervention in the GP
      contract. PCTs in the West Midlands are pioneering a range of initiatives,
      including the employment of specialised alcohol workers.

PMID- 14702853
TI  - Hearing aids. Loud and clear.
AB  - Improvements in hearing aid provision has been hampered by long waiting lists and
      a shortage of staff. Pilots last year showed the potential to increase capacity
      by using private sector capacity. A partnership between the NHS, the voluntary
      sector and two companies provides digital hearing aids free.

PMID- 14702854
TI  - Mental health. No way through.

PMID- 14702855
TI  - Law. It's a wrap.

PMID- 14702856
TI  - HSJ people. Stars and stripes.

PMID- 14702857
TI  - The global epidemic of tobacco and cancer.
AB  - OBJECTIVES: To provide a global context for understanding the epidemic of tobacco
      induced disease, and the need for nursing action. DATA SOURCES: International
      cancer and tobacco statistics; published articles. CONCLUSION: Tobacco use is a
      global problem and a significant issue for cancer control. The efforts of health
      professionals, especially those concerned about cancer, are needed to confront
      this epidemic. IMPLICATIONS FOR NURSING PRACTICE: Worldwide action of nurses, the
      largest group of health professionals, is critical in preventing tobacco use,
      helping with tobacco cessation, and decreasing exposure to second-hand smoke.

PMID- 14702858
TI  - Tobacco-related diseases.
AB  - OBJECTIVE: To provide an overview of the disease risks associated with cigarette
      smoking and the benefits of smoking cessation. DATA SOURCES: Government reports
      and monographs, and research articles. CONCLUSION: Cigarette smoking causes over
      400,000 deaths per year and is a major cause of coronary heart disease, chronic
      obstructive pulmonary disease, and lung cancer. The disease risks associated with
      cigarette smoking are proportional to the intensity and duration of smoking.
      Cessation of cigarette smoking results in a decline in risk in relation to the
      risks of continuing smokers. IMPLICATIONS FOR NURSING PRACTICE: Clinicians must
      be aware of the magnitude of smoking-related risks and the benefits of smoking
      cessation as a critical intervention.

PMID- 14702859
TI  - Tobacco use and dependence.
AB  - OBJECTIVES: To review tobacco use and dependence including nicotine pharmacology
      and addiction, and pharmacologic treatment. DATA SOURCES: Professional journals,
      books, government publications. CONCLUSION: Smoking is addictive and a major
      health problem. Habitual nicotine use is central to sustaining smoking
      dependence. This article provides the necessary basis for understanding nicotine
      addiction and pharmacologic therapies. IMPLICATIONS FOR NURSING PRACTICE: Nurses'
      knowledge about nicotine addiction is important in helping patients to quit
      smoking.

PMID- 14702860
TI  - Preventing cancer by controlling youth tobacco use.
AB  - OBJECTIVES: To review the epidemiology and prevention of teen smoking and the
      risks of smoking among survivors of childhood cancer. DATA SOURCES: Research
      articles, government reports, and surveys. CONCLUSION: Nicotine dependence often
      begins with the first few cigarettes smoked during adolescence. Teen tobacco use
      is fueled by the attractive social images that tobacco companies create for their
      products. Curtailing the sale of tobacco to minors and increasing their price
      decreases availability. Banning smoking in schools and public places reduces
      smoking opportunities. IMPLICATIONS FOR NURSING PRACTICE: Nurses have an
      important role to play in the battle against tobacco-induced malignancies through
      collaboration with community efforts or state initiatives.

PMID- 14702861
TI  - Smoking cessation and cancer.
AB  - OBJECTIVES: To provide an overview of scientifically based smoking cessation
      interventions for delivery to all tobacco-dependent users. DATA SOURCES: Research
      studies, published articles, and government reports. CONCLUSION: Smoking
      cessation interventions for patients with cancer remain poorly described with
      only a few studies investigating the efficacy of smoking cessation among this
      population. However, data suggest that quitting smoking after the diagnosis of
      cancer improves survival and quality of life. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses serve a critical role in tobacco-dependence treatment. Innovative
      interventions for cessation, such as quit lines, telephone counseling, web-based
      information, and computerized cessation materials are now available.

PMID- 14702862
TI  - Populations at risk for tobacco-related diseases.
AB  - OBJECTIVES: To provide an overview of US population groups at particular risk for
      tobacco-related diseases. DATA SOURCES: Surgeon General's reports, other official
      reports, published articles, research studies. CONCLUSION: The burden of tobacco
      related health alterations in known and less known population groups with reduced
      or absent access to primary health care services, infer that epidemiologic
      measures may be underestimated. Underestimations of these persons at risk have
      implications for future resource planning, allocation, and service. IMPLICATIONS
      FOR NURSING PRACTICE: Nurses can assist in the identification of and access to at
      risk populations before morbidities are at a late stage of diagnosis.

PMID- 14702863
TI  - Preventing exposure to second-hand smoke.
AB  - OBJECTIVE: To report the effectiveness of a health education intervention
      provided by nurses to prevent second-hand smoke exposure in sick children in Hong
      Kong. DATA SOURCES: A clinical trial, international and national government
      reports, and research studies. CONCLUSION: Exposure to second-hand smoke is
      associated with significant morbidity and mortality. Nursing interventions to
      reduce exposure are critical and need further study. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses are in a vital position to carry out health education about the
      health risks associated with second-hand smoke exposure and to protect the child
      from such exposure.

PMID- 14702864
TI  - Tobacco control policies.
AB  - OBJECTIVES: To review and summarize tobacco control policies, their impact in
      curbing the tobacco epidemic, and to describe a role for nursing advocacy. DATA
      SOURCES: Published articles and research studies. CONCLUSION: Comprehensive
      tobacco control policy is one of the most effective mechanisms to prevent tobacco
      related cancers and other illnesses. The World Health Organization's Framework
      Convention on Tobacco Control, and the Master Settlement Agreement in the United
      States have provided new opportunities for tobacco control. Nursing participation
      in the policy process can expand and strengthen these policies' activities.
      IMPLICATIONS FOR NURSING PRACTICE: Involvement in tobacco control should be
      integral to oncology nursing efforts to prevent cancer, promote health, and
      quality of life.

PMID- 14702865
TI  - International efforts in tobacco control.
AB  - OBJECTIVES: To review international nursing involvement in tobacco control and
      discuss opportunities and challenges to enhance nurses' participation in
      decreasing tobacco-related morbidity and mortality. DATA SOURCES: Published
      literature and published and unpublished material developed by nurses in their
      tobacco control initiatives. CONCLUSION: Worldwide, nurses have been involved in
      tobacco control. However, many opportunities remain for involvement in the areas
      of education, research, and practice. IMPLICATIONS FOR NURSING PRACTICE: There
      are numerous opportunities for nurses throughout the world to enhance their
      involvement in tobacco control.

PMID- 14702866
TI  - Generation of hair cells: a monumental breakthrough.

PMID- 14702867
TI  - Temporal bone fracture with hemotympanum.

PMID- 14702868
TI  - An asymptomatic foreign body in a maxillary sinus ostium.

PMID- 14702869
TI  - Vocal fold plaque following triamcinolone injection.

PMID- 14702870
TI  - CSF fistula secondary to sphenoid meningoencephalocele.

PMID- 14702871
TI  - Bronchial stricture secondary to pill aspiration.

PMID- 14702872
TI  - Electronystagmography in a woman with dizziness, tinnitus, and headache.

PMID- 14702873
TI  - Basics of practice management information technology.

PMID- 14702874
TI  - Papillary cystadenoma lymphomatosum (Warthin tumor).

PMID- 14702875
TI  - Giant-cell reparative granuloma of the temporal bone: a case report and review of
      the literature.
AB  - Giant-cell reparative granuloma (GCRG) is an unusual, non-neoplastic fibrous
      lesion that most often arises in the mandible and maxilla. GCRG of the temporal
      bone is exceedingly rare. To the best of our knowledge, only 17 cases have been
      previously reported in the international medical literature. Although no case of
      metastasis has been reported, this malignancy can be locally aggressive, and it
      often recurs following incomplete excision. We report the case of a young woman
      with a very large GCRG of the right temporal bone. We discuss the clinical
      picture, differential diagnosis, histologic evaluation, appearance on computed
      tomography and magnetic resonance imaging, and treatment options. We also review
      the cases of temporal bone GCRG that have been reported in the literature so far.

PMID- 14702876
TI  - Mandibular ameloblastoma and maxillary adenoid cystic carcinoma: case report.
AB  - We report the case of a 74-year-old woman who developed a follicular
      ameloblastoma of the right mandible and 22 months later developed a cribriform
      adenoid cystic carcinoma of the soft palate on the right maxilla. The
      ameloblastoma was treated by hemimandibulectomy, and the adenoid cystic carcinoma
      was managed by resection of the soft palate and the surrounding tissue and bone
      followed by a 6-week course of radiotherapy. Our review of the literature
      indicates that only one similar case has been previously reported where an
      odontogenic tumor and a salivary gland tumor involved two different anatomic
      locations in the same patient at nearly the same time.

PMID- 14702877
TI  - An unusual case of external ear inflammation caused by sarcoidosis.
AB  - Inflammation of the pinna can occur in conjunction with polychondritis and otitis
      externa. We describe a case of pinneal inflammation that proved to be
      sarcoidosis, and we discuss the otolaryngologic manifestations of sarcoidosis.

PMID- 14702878
TI  - Hydrodissection for complete removal of a ranula.
AB  - Hydrodissection has been used in various surgical fields to facilitate excision
      in both routine and difficult cases. This procedure involves the injection under
      pressure of saline and lidocaine with 1:100,000 epinephrine into the dissection
      plane. Removing a ranula without rupturing it can be a tedious and time-consuming
      process. Therefore, we used hydrodissection to assist us in performing these
      procedures. To review our experience with the treatment of ranulas, we performed
      a retrospective study of 38 patients who had undergone hydrodissection for ranula
      removal between January 1996 and December 2002 at our academic tertiary care
      hospital. Compared with other removal techniques, we found that hydrodissection
      was associated with less bleeding, fewer incidents of neural and soft-tissue
      damage, and a lower recurrence rate. In addition to reporting our study results,
      we also describe our hydrodissection technique, which is relatively simple,
      effective, and convenient for otolaryngologists.

PMID- 14702879
TI  - Cervical emphysema secondary to pneumomediastinum as a complication of
      childbirth.
AB  - Pneumomediastinum and cervical emphysema usually occur following esophageal or
      chest trauma. Rarely do they occur as a complication of childbirth, and only
      approximately 200 such cases have been reported in the literature worldwide. We
      describe a new case, and we review the clinical picture, pathophysiology, and
      management of these conditions. In view of the head and neck symptoms of
      pneumomediastinum and cervical emphysema during labor--which include dyspnea,
      cough, sore throat, pain on swallowing, and dysphagia--otolaryngologists might be
      consulted and should therefore be aware of these conditions in order to recognize
      and treat them.

PMID- 14702880
TI  - Lumpers versus splitters.

PMID- 14702881
TI  - Pilot study: quality of life assessment of postnatal fatigue and other physical
      morbidity.
AB  - Postnatal morbidity is increasingly recognized, but standard assessments may not
      capture what is most important to the woman with such morbidity in terms of her
      quality of life. The Mother-Generated Index (MGI) is a proposed postnatal quality
      of-life instrument which allows the mother to determine both content and scoring.
      In this pilot study we found that although a degree of psychological and physical
      morbidity (including tiredness) is common, and may be very significant, for most
      women these factors are low-grade, and other aspects of their lives are more
      important. A quality-of-life approach allows the mother to determine her own
      postnatal assessment, and encourages practitioners to view her more holistically.

PMID- 14702882
TI  - Definitions of women's sexual dysfunction reconsidered: advocating expansion and
      revision.
AB  - In light of various shortcomings of the traditional nosology of women's sexual
      disorders for both clinical practice and research, an international multi
      disciplinary group has reviewed the evidence for traditional assumptions about
      women's sexual response. It is apparent that fullfilment of sexual desire is an
      uncommon reason/incentive for sexual activity for many women and, in fact, sexual
      desire is frequently experienced only after sexual stimuli have elicited
      subjective sexual arousal. The latter is often poorly correlated with genital
      vasocongestion. Complaints of lack of subjective arousal despite apparently
      normal genital vasocongestion are common. Based on the review of existing
      evidence-based research, many modifications to the definitions of women's sexual
      dysfunctions are recommended. There is a new definition of sexual interest/desire
      disorder, sexual arousal disorders are separated into genital and subjective
      subtypes and the recently recognized condition of persistent sexual arousal is
      included. The definition of dyspareunia reflects the possibility of the pain
      precluding intercourse. The anticipation and fear of pain characteristic of
      vaginismus is noted while the assumed muscular spasm is omitted given the lack of
      evidence. Finally, a recommendation is made that all diagnoses be accompanied by
      descriptors relating to associated contextual factors and to the degree of
      distress.

PMID- 14702883
TI  - Attitudes toward menstruation in premenstrual dysphoric disorder: a preliminary
      report in an urban Turkish population.
AB  - The manner in which menstruation, femininity and the role of the mother are
      perceived, along with the social influences, are emphasized in the psychosocial
      dimension of premenstrual syndrome. This study attempts to investigate the
      perception of mothers and attitudes toward menstruation of a group of women
      diagnosed with premenstrual dysphoric disorder (PMDD) in a secular Muslim
      country. Thirty women with PMDD and 24 healthy women were studied using a semi
      structured questionnaire. Menstrual attitude and the way the mother was perceived
      in the childhood-to-puberty period by women with PMDD, were significantly
      negative in comparison to the control group. In conclusion, menstrual attitudes
      and premenstrual experiences of women should be investigated cross-culturally and
      prospectively.

PMID- 14702884
TI  - The influence of gestational age on depressive reactions, stress and anxiety of
      pregnant women and their partners in relation to prenatal diagnosis.
AB  - Prenatal diagnosis is usually performed in the early weeks of gestation in order
      to avoid medical and emotional maternal risks in the event of fetal malformation.
      This study examines emotions such as depression, stress and anxiety in pregnant
      women and their partners with regard to the week of gestation in which the
      prenatal diagnosis was made. In total, 452 pregnant women (between 7 and 40
      weeks' gestation) and 274 partners participated in this study. The pregnant women
      were divided into four groups of 113 subjects each according to length of
      pregnancy (group 1 = 7-15 weeks' gestation, group 2 = 16-18 weeks' gestation,
      group 3 = 19-23 weeks' gestation and group 4 = 24-40 weeks' of gestation).
      Depression, stress and Spielberger state-trait anxiety levels were measured
      before the prenatal examination, and stress and state anxiety were assessed after
      prenatal examination. Statistical analysis was performed using analysis of
      variance (ANOVA). After the prenatal examination, the mean values of state
      anxiety (p = 0.032) and stress (p = 0.030) showed statistically significant
      differences in the pregnant women. Their partners only showed statistically
      significant differences in the stress values (p = 0.048) after examination. In
      conclusion, emotional stress related to the prenatal diagnosis seems to be
      largely independent of gestational age. Ultrasound scans give the parents-to-be a
      clearer image of their unborn child, as their perception of the fetus is
      transformed from that of an anonymous object into an individual.

PMID- 14702885
TI  - Self-reported crying during the menstrual cycle: sign of discomfort and emotional
      turmoil or erroneous beliefs?
AB  - Crying is generally associated with distress and discomfort, and is also part of
      the premenstrual syndrome in women. The present studies focussed on crying
      fluctuations during the menstrual cycle. First, a retrospective cross-cultural
      study of women from 33 different countries (n = 2447) was conducted. Crying
      proneness reportedly increased before menstruation, with remarkable cross
      cultural differences. Women who were using oral contraceptives (OC) reported
      largely the same pattern of results as women who were not using OC. In a second
      study, 82 Dutch students kept a crying and mood diary for two consecutive
      menstrual cycles. During no phase of the menstrual cycle did actual crying
      episodes or crying proneness increase, although significant changes in mood were
      reported. Given the large cross-cultural differences on the one hand, and the
      remarkable correspondence between the self-reports of those using OC and those
      who did not use them on the other, it is concluded that the role of female sex
      hormone fluctuations in crying has to be questioned. Rather, it seems more likely
      that fluctuations in self-reported crying are based on implicit theories about
      the relationship between the menstrual cycle, mood and crying.

PMID- 14702886
TI  - Postpartum mood disorders: a review of clinical and epidemiological factors.
AB  - The postpartum period is a time of risk for mood disturbance in women. Postpartum
      blues occurs commonly, but is self-limited. Postpartum depression occurs in 13%
      of postpartum women. However, it is estimated that nearly one-half of all cases
      go undetected. Postpartum psychosis is rare, affecting 1-2 per 1000 women.
      Postpartum mood disorders can have far-reaching consequences and have been shown
      to affect the social and psychological development of children. It is critical
      that healthcare providers understand these disorders and their risk factors to
      increase detection and to educate women about the risks and treatments of
      postpartum mood disorders. This review is intended to provide healthcare
      providers with a better understanding of the descriptive epidemiology, risk
      factors, and treatments of postpartum mood disorders. The utility of specific
      screening instruments is also discussed.

PMID- 14702887
TI  - Psychiatric symptoms in Turkish infertile women.
AB  - The aims of this study were to determine the psychiatric symptoms which may
      develop because of infertility in Turkish women and to find out the precipitating
      factors. Fifty women with primary infertility and 50 health controls were
      evaluated using the Beck Depression Inventory, Spielberger Stait-Trait Anxiety
      Inventory, Rosenberg self-esteem scale and Symptom Checklist scale. They were
      also asked to describe the reactions received from their husband, husbands'
      families and social group because of infertility. Psychiatric symptoms were not
      significantly different between the two groups. However, within the infertile
      group, depression and anxiety were more frequent in the women who received
      negative reactions from their husband, their husbands' families and social group.
      Depression, anxiety and self-esteem were improved in the infertile women as age
      and the duration of infertility increased. In conclusion, our findings indicate
      that the reactions the infertile women are faced with play an important role in
      the development of certain psychiatric symptoms.

PMID- 14702888
TI  - The cook, the thief, his wife and her lover: on the evolution of the human
      reproductive strategy.
AB  - Human reproductive strategy differs from that of most other mammals, including
      Apes such as the closely related chimpanzee (Pan troglodytes) and the bonobo (Pan
      paniscus). For example, humans, although basically polygamic, exhibit a strong
      tendency to (serial) monogamy and--very rare for a mammal--provide biparental
      care. Moreover, humans are (almost) permanently willing to mate but, in contrast
      to other species, do so only in private. Unlike chimpanzees and bonobos, the
      human female exhibits no external signs of ovulation; rather a number of bodily
      features, e.g. permanently swollen milk glands and the quality of skin and hair,
      indicate fitness to breed. Human males also exhibit qualities that are rare among
      mammals: fertile males can be in the company of fertile females without sex being
      an imperative--although the awareness of sexuality is generally omnipresent.
      Moreover, unlike most other Apes, human males can cooperate in large groups, in
      spite of their polygynic inclination and their tendency to compete with each
      other for access to females. This capacity probably evolved in response to the
      necessity to acquire food, in particular meat, which was difficult to obtain by a
      single man. But life in large, complex, multi-male, multi-female groups places
      great demands on the members' social skills and, to be able to meet these
      demands, a large, sophisticated brain (neocortex) is needed. Food (and in its
      wake, cooking) probably forced man to live in ever-larger groups and to evolve
      the capacity to cooperate. This, in its turn, drove man's present-days
      psychosocial (emotional and intellectual) make-up. But for this to evolve, an
      adaptation of reproductive strategy was a conditio sine qua non.

PMID- 14702889
TI  - Fleet feedback.

PMID- 14702890
TI  - Assessing your AED need.

PMID- 14702891
TI  - Six keys to success.

PMID- 14702892
TI  - Will my safety harness save my life?

PMID- 14702893
TI  - Keep your eye on the individual's visual function, Part 2.

PMID- 14702894
TI  - Designing a balanced fire protection plan.

PMID- 14702895
TI  - Do you have an evacuation plan that works?

PMID- 14702896
TI  - Lost in the translation.

PMID- 14702897
TI  - The revised NFPA 30.

PMID- 14702898
TI  - The lowdown on regulatory reporting.

PMID- 14702899
TI  - Putting accident intervention systems into action.

PMID- 14702900
TI  - Where now with clinical computer systems?

PMID- 14702901
TI  - Delayed prescriptions in primary care.

PMID- 14702902
TI  - Automated quality checks on repeat prescribing.
AB  - BACKGROUND: Good clinical practice in primary care includes periodic review of
      repeat prescriptions. Markers of prescriptions that may need review have been
      described, but manually checking all repeat prescriptions against the markers
      would be impractical. AIM: To investigate the feasibility of computerising the
      application of repeat prescribing quality checks to electronic patient records in
      United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test
      against benchmark manual analysis of cross-sectional convenience sample of
      prescribing documentation. SETTING: Three general practices in Greater
      Manchester, in the north west of England, during a 4-month period in 2001.
      METHOD: A machine-readable drug information resource, based on the British
      National Formulary (BNF) as the 'gold standard' for valid drug indications, was
      installed in three practices. Software raised alerts for each repeat prescribed
      item where the electronic patient record contained no valid indication for the
      medication. Alerts raised by the software in two practices were analysed
      manually. Clinical reaction to the software was assessed by semi-structured
      interviews in three practices. RESULTS: There was no valid indication in the
      electronic medical records for 14.8% of repeat prescribed items. Sixty-two per
      cent of all alerts generated were incorrect. Forty-three per cent of all
      incorrect alerts were as a result of errors in the drug information resource, 44%
      to locally idiosyncratic clinical coding, 8% to the use of the BNF without
      adaptation as a gold standard, and 5% to the inability of the system to infer
      diagnoses that, although unrecorded, would be 'obvious' to a clinical reading the
      record. The interviewed clinicians supported the goals of the software.
      CONCLUSION: Using electronic records for secondary decision support purposes will
      benefit from (and may require) both more consistent electronic clinical data
      collection across multiple sites, and reconciling clinicians' willingness to
      infer unstated but 'obvious' diagnoses with the machine's inability to do the
      same.

PMID- 14702903
TI  - Patients' responses to delayed antibiotic prescription for acute upper
      respiratory tract infections.
AB  - BACKGROUND: Upper respiratory tract infections (URTIs) account for approximately
      50% of antibiotic prescriptions in the United Kingdom. General practitioners
      (GPs) frequently issue such prescriptions simply because they believe that the
      patient expects it. Deferred prescribing (issuing a prescription, but with
      instructions to wait for no spontaneous improvement before deciding whether to
      use it) might address patients' expectations, while minimising actual antibiotic
      consumption. Although the technique is quite widely practiced, patients'
      attitudes and responses to it are unclear. AIMS: To establish the proportion of
      recipients who claim to consume their delayed antibiotic prescriptions. To elicit
      factors associated with patients' decisions to consume their antibiotics, and
      patients' confidence in taking this decision. DESIGN OF STUDY: Postal
      questionnaire survey. SETTING: Patients from 13 group practices in the south of
      England. METHODS: Patients who had received a delayed antibiotic prescription for
      URTI from their GP were posted a questionnaire 2 days after their consultation.
      RESULTS: Three hundred and seventy-four subjects were recruited of whom 256
      (68.4%) returned their questionnaires. Just over half (53.1%) of the responders
      claimed to have consumed their antibiotics. The majority of patients (87.1%) were
      confident about taking the decision as to whether to use their antibiotics, and
      92.5% would choose to receive a delayed prescription again. Subjects were more
      likely to take their antibiotics if their presenting symptoms included a fever or
      sinus pain. CONCLUSION: Most patients are confident in making the decision about
      whether or not to take their antibiotics when receiving a delayed prescription
      for URTIs. Antibiotic consumption is associated with presenting symptoms, and
      this has implications for future practice.

PMID- 14702904
TI  - Patients' and physicians' perceptions and experience of hypercholesterolaemia: a
      qualitative study.
AB  - BACKGROUND: A better understanding of patients' and physicians' perceptions and
      experience of hypercholesterolaemia will help to improve cardiovascular disease
      prevention and aid the development of appropriate educational strategies. AIM: To
      identify perceptions, experience, educational needs, and barriers to learning in
      hypercholesterolaemic patients at high risk of cardiovascular disease. DESIGN OF
      STUDY: A qualitative study involving interviews with 27 hypercholesterolaemic
      outpatients and 21 physicians. SETTING: 21 centres in Paris, Bordeaux and Lille.
      METHODS: Semi-structured interviews were conducted by a sociologist with the aid
      of two interview guides focusing on hypercholesterolaemia. Interviews were
      recorded and subsequently transcribed, and qualitative analysis was performed to
      identify emerging themes. RESULTS: Six main themes emerged: understanding
      hypercholesterolaemia--a 'virtual' disease; understanding cardiovascular risk--a
      vague concept; lifestyle measures; long-term effects of medication; medical
      language difficulties; and patients' expectations and needs. Patients and
      physicians disagreed over the terms used to describe hypercholesterolaemia and
      cardiovascular risk, and the complexities of medical language. In contrast,
      patients and physicians agreed on the difficulties associated with implementing
      lifestyle changes and adhering to long-term treatment. CONCLUSIONS: The
      differences in perception and experience between physicians and patients indicate
      that physician-patient communication is sub-optimal and highlights the need to
      improve educational material for cardiovascular disease prevention. This analysis
      helps to identify appropriate educational objectives and methods for patients at
      risk of cardiovascular disease, and develop a structured educational programme.

PMID- 14702905
TI  - Sexual violence against adult women primary care attenders in east London.
AB  - BACKGROUND: Sexual violence against women is common. The prevalence appears to be
      higher in north America than Europe. However, not all surveys have differentiated
      the experience of forced sex by a current or former partner. Few women are
      thought to report these experiences to their general practitioner (GP). AIM: To
      measure the prevalence of rape, sexual assault, and forced sexual intercourse by
      a partner among women attending general practices, to test the association
      between these experiences of sexual violence and demographic factors, and to
      assess the acceptability to women of screening for sexual violence by GPs. DESIGN
      OF STUDY: Cross-sectional survey. METHOD: A self-administered questionnaire
      survey of 1207 women aged over 15 years was carried out in 13 general practices
      in Hackney, east London. RESULTS: Eight per cent (95% confidence interval [CI] =
      6.2 to 9.6) of women have experienced rape, 9% (95% CI = 7.0 to 10.6) another
      type of sexual assault, and 16% (95% CI = 13.6 to 18.1) forced sex by a partner
      in adulthood: 24% (95% CI = 21.2 to 26.5) have experienced one or more of these
      types of sexual violence. Experiences of sexual violence demonstrated high levels
      of lifetime co-occurrence. Women forced to have sex by partners experienced the
      most severe forms of domestic violence. One in five women would object to routine
      questioning about being raped and/or sexually assaulted, and one in nine about
      being forced to have sex by a partner. CONCLUSION: Experiences of sexual violence
      are common in the lives of adult women in east London, and they represent a
      significant public health problem. Those women who have one experience appear to
      be at risk of being victims again. A substantial minority object to routine
      questions about sexual violence.

PMID- 14702906
TI  - Partnership effects in general practice: identification of clustering using intra
      class correlation coefficients.
AB  - Although most United Kingdom general practitioners (GPs) work together in a
      shared professional arrangement termed 'partnership', little is known about the
      nature of such partnerships. We report the results of a survey of 61 general
      practice partners in 15 group practices and their attitudes to prescribing and
      managerial issues related to participation in a commissioning group. Intra-class
      correlation coefficients (ICCs) were used to explore how these individually held
      attitudes clustered within groups. The low ICCs found for attitudes relating to
      prescribing issues suggested that GPs acted individually in this respect, while,
      in contrast, responses to managerial questions clustered strongly in
      partnerships, implying that managerial attitudes were more likely to be shared
      within partnerships. The ICC statistic is a useful tool for exploring homogeneity
      and heterogeneity within general practice partnerships.

PMID- 14702907
TI  - A nationwide adaptive prediction tool for coronary heart disease prevention.
AB  - Standardised electronic recording of cardiovascular risk factor data collected
      during primary care delivery could be used to create a new strategy, using an
      adaptive prediction model, for targeting primary prevention interventions at high
      risk individuals. In the short term, this should progressively improve data
      quality and allow risk modification to be monitored at the population level. In
      the long term, feedback of data on cardiovascular disease development might
      enable the model to tailor the recommended interventions more appropriately to
      the needs of the individual and to adapt to future changes in risk patterns.
      Ultimately, the inclusion of additional cardiovascular risk factors might enable
      a richer, more realistic picture of cardiovascular risk profiles to be uncovered.
      This model may have wider uses in both research and practice, and provides a
      further incentive for the standardisation of record keeping in primary care.

PMID- 14702908
TI  - Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A
      systematic review.
AB  - BACKGROUND: There is concern about the increasing resistance of antibiotics to
      common bacteria. Delayed prescribing for respiratory tract infections is a
      strategy that may reduce the use of antibiotics. AIM: To systematically review
      controlled trials of delayed prescriptions to establish their capacity to reduce
      antibiotic intake. DESIGN OF STUDY: A systematic review of the literature.
      SETTING: Four studies were conducted in the United Kingdom and one in New
      Zealand. METHODS: We searched MEDLINE from 1966 to April 2003, EMBASE, and the
      Cochrane Controlled Trials Register using the following terms: 'delayed',
      'antibiotics', 'prescriptions', and 'back-up' (as in back-up prescription). We
      included controlled trials of studies in which the intervention was a delayed
      prescription compared to an immediate prescription for patients with upper
      respiratory tract infections. The studies were selected independently and the
      results compared. Disagreements were resolved by discussion. The data and quality
      of the studies were extracted and assessed independently by two of the authors.
      RESULTS: Four randomised controlled trials and one before-after controlled trial
      contributed to the review. The relative risk in the randomised trials for lower
      antibiotic usage when a delayed prescription was given ranged from 0.54 for the
      common cold to 0.25 for otitis media. CONCLUSION: The consistent reduction in
      antibiotic usage in the five controlled trials included in this review suggests
      that delayed prescription is an effective means of reducing antibiotic usage for
      acute respiratory infections. The duration of delay for prescriptions ranged
      widely, from 1 to 7 days.

PMID- 14702909
TI  - A systematic review of the effect of primary care-based service innovations on
      quality and patterns of referral to specialist secondary care.
AB  - BACKGROUND: Innovations are proliferating at the primary-secondary care
      interface, affecting referral to secondary care and resource use. Evidence about
      the range of effects and implications for the healthcare system of different
      types of innovation have not previously been summarised. AIM: To review the
      available evidence on initiatives affecting primary care referral to specialist
      secondary care. SETTING: Studies of primary-secondary care interface. METHOD:
      Systematic review of trials, using adapted Cochrane Collaboration (effective
      practice and organisation of care) criteria. Studies from 1980 to 2001 were
      identified from a wide range of sources. Strict inclusion criteria were applied,
      and relevant clinical, service and cost data extracted using an agreed protocol.
      The main outcome measures were referral rates to specialist secondary care.
      RESULTS: Of the 139 studies initially identified. 34 met the review criteria. An
      updated search added a further 10 studies. Two studies provided economic analysis
      only. Referral was not the primary outcome of interest in the majority of
      included studies. Professional interventions generally had an impact on referral
      rates consistent with the intended change in clinician behaviour. Similarly,
      specialist 'outreach' or other primary care-based specialist provider schemes had
      at least a small effect upon referral rates to secondary care with the direction
      of effect being that intended or rational from a clinical and sociological
      perspective. Of the financial interventions, one was aimed primarily at changing
      the numbers or proportion of referrals from primary to specialist secondary care,
      and the direction of change was as expected in all cases. The quality of the
      reporting of the economic components of the 14 studies giving economic data was
      poor in many cases. When grouped by intervention type, no overall pattern of
      change in referral costs or total costs emerged. CONCLUSION: The studies
      identified were extremely diverse in methodology, clinical subject,
      organisational form, and quality of evidence. The number of good quality
      evaluations of innovative schemes to enhance the existing capacity of primary
      care was small, but increasing. Well-evaluated service initiatives in this area
      should be supported. Organisational innovations in the structure of service
      provision need not increase total costs to the National Health Service (NHS),
      even though costs associated with referral may increase. This review provides
      limited, partial, and conditional support for current primary care-oriented NHS
      policy developments in the United Kingdom.

PMID- 14702910
TI  - Barriers between community pharmacists and GPs.

PMID- 14702911
TI  - Barriers to the use of statins.

PMID- 14702912
TI  - Barriers to the use of statins.

PMID- 14702913
TI  - Early complications of circumcisions performed in the community.

PMID- 14702914
TI  - Turning the tide on drugs.

PMID- 14702915
TI  - Managing complications in cancer: identifying and responding to the patient's
      perspective.
AB  - OBJECTIVES: To describe psychosocial problems experienced by cancer patients and
      present assessment tools to evaluate these issues and develop effective
      management programs. DATA SOURCES: Published literature and clinical experience.
      CONCLUSION: A screening program may identify patients needing psychologic
      evaluation and treatment and reduce distress for patients and caregivers.
      IMPLICATIONS FOR NURSING PRACTICE: Use of screening tools allows critical
      decisions to be made regarding treatment for patients with high levels of
      distress, fatigue, and other conditions.

PMID- 14702916
TI  - Recent advances in adjuvant therapy for breast cancer.
AB  - OBJECTIVES: To review recent studies that may influence the adjuvant treatment of
      patients with breast cancer. Studies reviewed evaluate the role of aromatase
      inhibitors, incorporation of taxanes into chemotherapy regimens, novel dosage
      schedules, and supportive care with epoetin alfa. DATA SOURCES: Published
      literature and clinical experience. CONCLUSION: Recent evidence suggests that
      aromatase inhibitors are more effective than tamoxifen as hormonal adjuvant
      therapy and that the addition of taxanes to adjuvant chemotherapy improves
      outcome. Supportive care is also an important component of therapy. IMPLICATIONS
      FOR NURSING PRACTICE: Knowledge of recent advances in adjuvant therapy for breast
      cancer will contribute to greater efficacy in patient care.

PMID- 14702917
TI  - Chemotherapy-related cognitive dysfunction in breast cancer.
AB  - OBJECTIVES: To provide an overview of chemotherapy-related cognitive dysfunction
      in breast cancer survivors, focusing on its pathophysiology, risk factors,
      assessment, and management. DATA SOURCES: Published biomedical literature.
      CONCLUSION: Chemotherapy-related cognitive dysfunction in patients with breast
      cancer is multifactorial and possibly related to anemia or a direct effect of
      chemotherapy on brain function. Clinical observation and subjective reports are
      useful assessments. Therapies directed at alleviating or preventing cognitive
      deficits are being investigated. IMPLICATIONS FOR NURSING PRACTICE: Oncology
      nurses are important in monitoring cognitive function in patients with breast
      cancer receiving chemotherapy. Nurses who are aware of the risks, assessment, and
      management of cognitive impairment are better able to discuss these issues with
      patients and caregivers.

PMID- 14702918
TI  - Chemotherapy for newly diagnosed and relapsed advanced ovarian cancer.
AB  - OBJECTIVES: To review chemotherapy options for patients with newly diagnosed or
      relapsed advanced ovarian cancer. DATA SOURCES: Published literature. CONCLUSION:
      Primary chemotherapy for newly diagnosed, advanced ovarian cancer consisting of a
      platinum compound and a taxane is commonly associated with myelosuppression,
      nausea/vomiting, alopecia, and sensory/motor neuropathy. For recurrent disease,
      numerous chemotherapy agents are effective, including rechallenging the patient
      with a platinum and/or a taxane or using newer agents such as pegylated liposomal
      doxorubicin, topotecan, and gemcitabine. In platinum-resistant disease, selection
      is based mainly on the toxicity profile, because palliation and quality of life
      are important. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses play a valuable
      role in ovarian cancer care by proactively meeting patient information needs.

PMID- 14702919
TI  - Current management of fatigue and anemia in patients with cancer.
AB  - OBJECTIVES: To describe the management of fatigue and anemia in patients with
      cancer. DATA SOURCES: Published literature and clinical experience. CONCLUSION:
      Anemia is a common cause of cancer-related fatigue. Epoetin alfa increases
      hemoglobin, decreases transfusion requirements, and improves energy and quality
      of life in patients with cancer-related anemia. Nonpharmacologic treatment
      options include exercise, nutrition optimization, and psychosocial interventions.
      Effective management of fatigue improves overall cancer treatment, quality of
      life, and functional status. IMPLICATIONS FOR NURSING PRACTICE: Fatigue and
      anemia are commonly undertreated complications of cancer and its treatment.
      Oncology nurses play a key role in identifying and managing these conditions.

PMID- 14702920
TI  - [Follicular lymphoma].
AB  - Follicular lymphoma is one of the most common indolent nodal non-Hodgkin's
      lymphomas. The follicular lymphoma should be differentiated from other nodal non
      germinal centre derived lymphomas. Since bcl-2 gene translocation can be detected
      in 80-90% of the cases, it could be used for the confirmation of the diagnosis,
      measure of the treatment efficacy as well as for the evaluation of the prognosis
      and follow-up of the disease. There is no uniform therapy employed for follicular
      lymphoma patients. The treatment depends on the histological grade, stage, age
      and condition of the patients. Since disease cannot be cured by conventional
      dosage therapy in the vast majority of the cases, a treatment--adjusted to the
      condition of the patients as well as the stage and grade of the disease--ensuring
      the longest period and best quality of life should be selected. The authors
      review the questions of diagnosis and treatment, including the results of
      radiotherapy and chemotherapy and discuss the role of the interferon-alpha,
      purine analogues, monoclonal antibodies and high-dose therapy.

PMID- 14702921
TI  - [Possibilities of investigation and clinical application of adult human stem
      cells].
AB  - Multipotent adult tissue stem cells have high plasticity and transdifferentiation
      ability. The stem cell therapy can be the solution of curing many severe diseases
      such as osteogenesis imperfecta, hepatic failure, heart muscle damage after
      myocardial infarction, I-type diabetes, variety of central nervous system
      disorders such as brain injury, stroke, Parkinson's disease and other
      neurodegenerative disorders. Isolation of certain types of stem cells is solved
      nowadays, but low frequency of these cells and lack of special identification
      markers make their isolation and search more difficult. The more and more
      developed in vitro cell culture technologies, the widespread macromolecule
      amplification and examination techniques of molecular biology and the gene
      technology tools for genetic modification of stem (and other) cells contribute to
      research and therapeutic applications of stem cells. Transfer of new genetic
      material to stem cells and expression of the gene product in daughter cells-
      because missing or damaged genes can be replaced--is an exiting approach of the
      treatment of congenital (enzyme deficiencies) and acquired human diseases
      (cancers).

PMID- 14702922
TI  - [Human positron emission tomography with oral 11C-vinpocetine].
AB  - INTRODUCTION: Positron emission tomography (PET) is a useful tool for the
      investigation of certain physiological changes and for the evaluation of the
      distribution, and receptor binding of drugs labelled with positron emitting
      isotopes. Vinpocetine (ethyl-apovincaminate) is a neuroprotective drug widely
      used in the prevention and treatment of cerebrovascular diseases. In the clinical
      practice vinpocetine is usually administered to the patients in intravenous
      infusion followed by long-term oral treatment. Until presently human data
      describing vinpocetine's kinetics and brain distribution came from ex vivo
      (blood, plasma, liquor) and post mortem (brain autoradiography) measurements.
      AIM: The authors wished to investigate the kinetics and distribution of
      vinpocetine in the brain and body after oral administration with PET in order to
      prove, that PET is useful in the non-invasive in vivo determination of these
      parameters. METHOD: Vinpocetine was labelled with carbon-11 and the radioactivity
      was measured by PET in the stomach, liver, brain, colon and kidneys in healthy
      male volunteers. The radioactivity in the blood and urine was also determined.
      RESULTS: After oral administration, [11C]vinpocetine appeared immediately in the
      stomach and within minutes in the liver and the blood. In the blood the level of
      radioactivity continuously increased until the end of the measurement period,
      whereas the fraction of the unchanged mother compound decreased. Radioactivity
      uptake and distribution in the brain were demonstrable from the tenth minute
      after the oral administration of the labelled drug (average maximum uptake: 0.7%
      of the administered total dose). Brain distribution was heterogeneous (with
      preferences in the thalamus, basal ganglia and occipital cortex), similar to the
      distribution previously reported by the authors after intravenous administration.
      CONCLUSIONS: Vinpocetine, administered orally to human volunteers, readily
      entered the bloodstream from the stomach and the gastrointestinal tract and
      thereafter passed the blood-brain barrier and entered the brain. Radioactivity
      from [11C]vinpocetine was also demonstrated in the kidneys and in urine. The
      study demonstrates that PET might be a useful, direct and non-invasive tool to
      study the distribution and pharmacokinetics of orally administered labelled drugs
      active in the central nervous system in the living human body.

PMID- 14702923
TI  - [Employment and effectiveness of the BITE questionnaire in screening for eating
      disorders].
AB  - OBJECTIVE: The purpose of study was to describe a new briet questionnaire, the
      Bulimic Investigatory Test, Edinburgh (BITE), for detection of binge eating
      disorder and bulimia nervosa. METHOD: Description of the BITE test which was
      developed by Henderson and Freeman in 1987. The scale measures of both symptoms
      and severity by the eating disorders. RESULTS: Data from some Hungarian studies
      demonstrate satisfactory reliability and validity. The BITE test is well suited
      in the national circumstance to demonstrated the control lost status with binges
      and the predisposition to bulimia nervosa. The test alone it isn't enough to
      diagnose of binge eating disorders and bulimia nervosa. The test is well
      sensitive to measure the effectiveness of the therapy and the changes of
      symptoms. CONCLUSION: All items of BITE test are covered the diagnostic criteria
      by Diagnostic and Statistical Manual of Mental Disorders of bulimia nervosa. The
      BITE can be as a screening method for binge eating disorder in obese patients
      too.

PMID- 14702924
TI  - [Agenesis of inferior vena cava combined with multiple genetic predisposition in
      the case of deep venous thrombosis in a young male].
AB  - Deep venous thrombosis in the young age may be a complication of the rare
      congenital abnormality of the vena cava inferior. Genetic factors predisposing to
      thrombophilia in coincidence with vena cava malformation put the patients at much
      higher risk to develop thrombosis. The authors report a case of a 25-year old
      male who suffered from a massive deep venous thrombosis derived from the vena
      poplitea involving the vena iliaca communis. The molecular genetic examination of
      the patient revealed his combined genetic predisposition to venous thrombosis
      (Heterozygosity for Factor V. Leiden, Heterozygosity for prothrombin G20210A).
      Authors conclude that it is essential to perform all the relevant molecular
      genetic examinations to identify the presence of thrombophilic vulnerabilty and
      radiological imaging procedures in all cases of young patients with deep venous
      thrombosis if the suspicion of vascular malformation arises. The review of the
      literature revealed that the vena cava malformation in association with genetic
      factor predisposing to thrombophilia is an infrequent condition. In the authors
      knowledge this is the first report presenting a multiple combined genetic
      predisposition of risk factors in deep venous thrombosis.

PMID- 14702925
TI  - [Therapy in thyroid cancer].

PMID- 14702926
TI  - Overview of chemotherapy-induced diarrhea.
AB  - OBJECTIVES: To provide a general overview of chemotherapy-induced diarrhea (CID)
      that will highlight the pathophysiology, incidence, and impact of this problem,
      as well as describe the oncology nurse's role in the management of CID. DATA
      SOURCES: Primary and tertiary literature, the authors' clinical experience.
      CONCLUSION: CID is a frequent complication of many types of chemotherapy that can
      significantly affect patient quality of life, increase treatment costs, and limit
      the ability to deliver full doses of chemotherapy. Because patients may be
      reluctant to discuss diarrhea with their health care providers, vigilance on the
      part of the health care team is needed. IMPLICATIONS FOR NURSING PRACTICE:
      Through ongoing, regular patient contact, the oncology nurse is uniquely situated
      to monitor patients for the development of CID, assess its severity, and provide
      guidance to the health care team on the patient's status.

PMID- 14702927
TI  - Overview of radiation- and chemoradiation-induced diarrhea.
AB  - OBJECTIVES: To describe the pathophysiology, incidence, and impact of radiation
      induced diarrhea (RID), and to highlight the radiation oncology nurse's role.
      DATA SOURCES: Primary and tertiary literature, and clinical experience.
      CONCLUSION: RID is a frequent complication of pelvic radiation, both when given
      alone and with chemotherapy. RID can significantly affect patient quality of
      life. Since diarrhea may be a difficult topic for patients to discuss, special
      care needs to be taken to avoid underdiagnosis of this problem. IMPLICATIONS FOR
      NURSING PRACTICE: The oncology nurse is uniquely situated to monitor patients for
      the development of RID, assess its severity and provide guidance to the health
      care team on the patient's status.

PMID- 14702928
TI  - Management of acute cancer treatment-induced diarrhea.
AB  - OBJECTIVES: To describe the dietary and pharmacologic management of acute CTID.
      DATA SOURCES: Primary and secondary literature, and clinical experience.
      CONCLUSION: When dietary strategies do not work, or when patients present with
      grade 3/4 diarrhea, pharmacologic intervention is required. First-line therapy
      should be initiated quickly with loperamide or diphenoxylate/atropine in
      recommended doses. Somatostatin analogues are effective as second-line therapy or
      as first-line therapy for patients with grade 3/4 diarrhea. IMPLICATIONS FOR
      NURSING PRACTICE: Oncology nurses should strive to match treatment with the
      severity of symptoms of CTID. Whatever therapy is chosen, the goal must be to
      quickly control this debilitating and potentially life-threatening side effect so
      that primary chemotherapy and/or radiation therapy may be resumed and completed.

PMID- 14702929
TI  - New strategies for the prevention and reduction of cancer treatment-induced
      diarrhea.
AB  - OBJECTIVES: To describe possible new strategies for the prevention of CTID. DATA
      SOURCES: Abstracts presented at oncology meetings, primary and secondary
      literature, trial protocols, and clinical experience. CONCLUSION: Patients who
      have experienced an episode of diarrhea are at high risk for developing diarrhea
      with additional cycles of chemotherapy or radiation. One preventive strategy that
      holds out promise is the use of octreotide LAR as prophylaxis. This strategy
      should be considered for patients with a prior cycle complicated by persistent
      (lasting more than 48 hours) diarrhea of any severity, or by diarrhea of grades 3
      and higher. IMPLICATIONS FOR NURSING PRACTICE: With preventive intervention and
      aggressive management of breakthrough symptoms, CTID may no longer pose a
      significant threat to patient comfort and well-being.

PMID- 14702930
TI  - [Endoscopic sphincterotomy as an out-patient procedure: is it safe?].
AB  - BACKGROUND: Patients have been routinely admitted for observation for potential
      complications after therapeutic ERCP; however, in this era of cost containment it
      may be more cost-effective to perform these procedures on an out-patient basis.
      AIM: The purpose of this study was to determine safety and complication rates of
      endoscopic sphincterotomy in out-patients. MATERIALS AND PATIENTS: Over an 11
      month period, 124 consecutive patient undergoing endoscopic sphincterotomy for
      biliary and pancreatic disease were enrolled in a prospective and randomized
      manner. Sixty patients (Group A) were observed 1-3 h post procedure before
      discharge with follow-up at 5 days. The other 62 patients (Group B) were admitted
      for observation. The statistical method was Fisher test and chi 2. RESULTS:
      Successful endoscopic sphincterotomy was achieved in 98.3% (122/124) of patients.
      Eighty five patients were female and 37 male. There were 60 outpatients and 62 in
      patients; endoscopic sphincterotomy was performed by choledocholithiasis in 59.9%
      (70 cases) and papillary stenoses in 16.4% (20 cases). Complication rates were
      3.27% (four patients): three pancreatitis and one bleeding. There were three in
      patients and one outpatient (p. 313). We reduce costs $324,120.00 M.N. (Mexican
      pesos) without compromising patient safety and outcome. CONCLUSIONS: Endoscopic
      sphincterotomy may be performed safely on an outpatient basis, realizing
      significant savings in costs.

PMID- 14702931
TI  - [Surgical treatment of complete rectal prolapse. Experience at a colon and rectal
      surgery service].
AB  - BACKGROUND: Rectal prolapse is as ancient humanity. Treatment must be surgical in
      adult patients. There is no gold standard procedure to date; thus, this has given
      rise to controversy. OBJECTIVE: One objective was to analyze our results,
      complications, mortality, and recurrence in a Colorectal Surgery Service for
      surgical treatment of complete rectal prolapse. PATIENTS AND METHODS: We reviewed
      records of all patients treated surgically with rectal prolapse at our Service
      from March 1995 to March 2001. RESULTS: 31 patients; 22 were female and nine male
      with age range of 24 to 89 years. Evolution time was 6 months to 40 years; 11
      patients had preoperative incontinence. We carried our four procedures, abdominal
      procedure hospital stay was 4 to 7 days; we had 18% long-term complications with
      no mortality or recurrence. Hospital stay in perineal procedures was 1 to 2 days
      with one procedure associated with death due to AV blockade, with 14% recurrence
      for helicoidal suture procedure, and no complications. Altemeier procedure
      recurred at 1 month of surgery. Continence score of Miller improve
      postoperatively. CONCLUSIONS: Abdominal procedures have less recurrence than
      perineal procedures; abdominal procedures must be considered in young patients
      with low risk, and perineal procedures in older patients with high risk, that are
      coantraindications for a major surgical procedure.

PMID- 14702932
TI  - [Dietetic assessment of patients with gastroenterologic diseases at the out
      patient service of the Institute National of Sciences Medicine and Nutrition
      Salvador Zubiran].
AB  - Assessment of dietetic management is necessary for detection/correction of faults
      and best care of patients. AIM: Our aim was to evaluate dietetic management and
      nutritional status of gastroenterologic patients. METHODS: Anthropometric,
      clinical-nutritional, biochemical, and dietetic parameters were assessed in 110
      patients (150 with liver cirrhosis [LC], 30 with inflammatory bowel disease
      [IBD], and 30 with chronic and skin. In CP, prescribed energy, g and %
      carbohydrates and lipids were less than ideal and proteins were greater; in
      cirrhotics, less proteins and a great % of carbohydrates were prescribed; in IBD
      fewer lipids and more proteins than ideal were prescribed. Cirrhotics usually
      consumed less fat (g) and more proteins than prescribed, and patients with CP and
      IBD a greater amount of carbohydrates than prescribed. Cirrhotics consumed more %
      carbohydrates and < % lipids than ideal; CP patients lipid intake was less and
      protein intake above ideal and in IBD, carbohydrate intake was greater and lipid
      intake lower than ideal. CONCLUSIONS: Anthropometric and biochemical parameters
      were not useful for assessment of these patients. Prescribed diet was too
      restricted regarding proteins in LC and was inadequate in energy/nutrients in
      patients with CP. Fewer lipids and more proteins were prescribed in IBD. The
      inadequacy of prescripted diet, lack of information regarding the person who
      prescribed it, and lack of constant supervision may cause non-adherence to diet
      and thus may affect nutritional status.

PMID- 14702933
TI  - [Bipolar electrocoagulation in patients with persistent hemorrhage secondary to
      second degree postradiation proctopathy].
AB  - OBJECTIVE: Our objective was to evaluate response to bipolar electrocoagulation
      (BICAP) in patients with persistent rectorragia (PR) secondary to PRP (post
      radiation proctitis) degree II (telangiectasias). MATERIAL AND METHODS: We had 64
      cases prospective and conducted study cohort of 257 patients, with cervicouterine
      cancer, radiated, PRP degree II, and PR. DESIGN: We conducted prospective, cross
      sectional and descriptive study. Patients were divided in three groups: (group
      1), with hemodynamical instability; (group 2) with chronic anemia, and (group 3),
      without data of chronic anemia (Table 1). Clinical evaluation was carried out
      before and after the intervention (BICAP). BICAP of radial way at level of
      telangiectasias was applied, of sigmoides up to 2 cm of anal margin. Three
      sessions were average. RESULTS: A total of 55 patients had PR radiation dose
      average, with 49.85 Gy. Time average of appearance of rectorragia was 9 months.
      GROUP 1: A total of 21 patients, age 51.2 years average). Previous to BICAP, week
      by frequency of rectorragia was 2.23 (average). With hemoglobin (Hb) and
      hematocrit (Ht) of 7.1 g (average) and 24.4%, respectively (average). A total of
      18 patients (85.7%) required hemotransfusion. Average hospital stay was 1.3 days.
      Cardiac frequency, arterial, blood and hemoglobin pressure, and hematocrit
      obtained later improvement to intervention with BICAP was statistically
      significant (p > 0.0001). Patients did not require additional blood transfusions.
      GROUP 2: A total of 18 patients with age average 56 years (average). Previous to
      BICAP they had weekly rectorragia of 2.16 (average). Hb was 11.4 g and Ht of
      35.5% (average). Subsequent to BICAP, 100% patients had controlled hemostasis.
      The improvement observed with regard to cardiac frequency and blood pressure
      after application of BICAP did not have statistical significance despite the fact
      that it was demonstrated to laboratory parameters as well as diminution of weekly
      episodes of rectorragia if they were statistically significant (p > 0.0001). No
      blood transfusion was required. GROUP 3: There were 16 patients with average of
      57.1 years of age (average). Previous to BICAP they had weekly 1 rectorragia of
      2.06, Hb of 13.5 g and Ht of 41.2% (average). Subsequent to BICAP, there was 100%
      controlled haemostasis. In this group, diminution of weekly episodes of
      rectorragia, cardiac frequency, and blood pressure did not have statistically
      significant changes; nevertheless, hemoglobin and hematocrit had a statistically
      significant increase (p > 0.0001). No blood transfusion was required.
      CONCLUSIONS: Electrocoagulation (BICAP) is effective in hemostasis of bleeding
      telangiectasias, stabilizing to the patient, and diminishing recurrence, hospital
      stay, and blood requirements.

PMID- 14702934
TI  - [Wegener's granulomatosis of the colon. Case report and review of the
      literature].
AB  - INTRODUCTION: Wegener's granulomatosis is not very common and it is associated
      with colonic affection is extremely rare. It was first described by Klinger, and
      by Wegener in 1936. It is a systemic clinico-pathologic entity to be mediated by
      immune mechanisms. The most common clinical manifestations are of respiratory,
      renal, and vascular origins. Diagnosis is histologic. OBJECTIVE: Presentation of
      a clinical case and literature revision. MATERIAL AND METHODS: The patient was a
      46 year old male who vegan 3 years previously with symmetrical arthralgia in
      ankles and knees, cough, purulent expectoration, intermittend fever, occasional
      moderated hematoquezia, profuse diarrhea, and abdominal pain. The patient was
      subjected to laboratory and cabinet studies, by means of which it was established
      a diagnosis secondary colitis colonic mucosa. Definitive histopathologic study
      confirmed diagnosis of colonic Wegener's granulomatosis.

PMID- 14702935
TI  - [Myofibroblast tumor].
AB  - OBJECTIVE: Our objective was to present a case of inflammatory myofibroblastic
      tumor of the colon. BACKGROUND: Inflammatory myofibroblastic tumors are uncommon.
      They originate from soft tissues, their appearance is more frequent in childhood
      and your adulthood and these tumors are composed of myofibroblastic cells,
      leukocytes, and plasmatic cells. More frequently, these tumors originate in
      lungs, mesentery, liver and spleen; intestinal appearance is uncommon. METHOD: In
      a 42 year-old male with a lump in right iliac fossa, a colonic inflammatory
      myofibroblastic tumor infiltrating ileocecal valve was found. Right hemicolectomy
      was performed. After a 10-month follow-up, no complications were found and no
      adjuvant therapy was needed. CONCLUSIONS: Inflammatory myofibroblastic tumors
      have been well described, but, experience is quite limited; Symptoms are
      consequences of compressed organs in the vicinity. At present, no early detection
      devices are available, but genetical evaluations for the patient's family members
      may contribute to unravel a pattern of transmission of the disease.

PMID- 14702937
TI  - [Mesenteric cyst. A review].
AB  - The mesenteric cyst is a tumor of multiple origins, that undoubtedly presents
      with greater frequency than that referred in published series. Nevertheless, it
      continues to be a rare entity. Due to absence of characteristic signs and
      symptoms, diagnosis is only made once these lesions have reached a size,
      sufficiently large to be palpable or when they cause compression on organs or
      neighboring structures. The cyst can present with chronic manifestations such as
      diffuse abdominal pain imprecisely located but associated with palpable mass, or
      due to complications of the cyst or due to compression of adjacent structures.
      Diagnosis is confirmed by imaging studies, such as the different ultrasound
      modalities, computed tomography (CT) scan, and magnetic resonance imaging (MRI).
      A differential diagnosis must be made to exclude other intra-abdominal or retro
      peritoneal tumors. Optimum treatment is extirpation of the cyst. On occasion it
      is also necessary to remove the adjacent organ due to the impossibility of
      enucleating cyst. marsupialization of the cyst or drainage into peritoneal
      cavity, have high incidence of recurrence. Surgical treatment can be carried out
      by minimal invasion techniques.

PMID- 14702936
TI  - [Medico-surgical consensus for management of children with gastroesophageal
      reflux Acapulco, Mexico 2002].
AB  - Gastroesophageal reflux (GER) is a common disease in children less one year old.
      It is present around 10% of unselected infant population. 40-50% have abnormal 24
      h pH monitoring. An early diagnosis and treatment should be done in order to
      avoid complications. AIM: To establish the consensus for the diagnosis and
      treatment of children with GER, to rule out similar diseases avoid the use of
      unnecessary drugs and the secondary side effects as well as unnecessary surgery.
      METHOD: The consensus was done with the participation of general pediatricians,
      pediatrics gastroenterologist, pediatric surgeons, radiologist and endoscopist.
      An initial paper was done by pediatric surgeon and pediatric gastroenterologist
      who submitted to the rest of participants. Second stage: the paper was review
      through E-mail for all participants who send their suggestions and modifications.
      A new paper was done and discussed by medical and surgery area. During the
      Congress of Pediatric Surgery, in an open session was discuss again with the
      participation of the main authors and all the audience present. Finally, a paper
      was done and review for the main authors.

PMID- 14702938
TI  - [Interferon-alpha and liver fibrosis in patients with chronic damage due to
      hepatitis C virus].
AB  - The present review focuses on the published information published regarding the
      effects of interferon alpha therapy on liver fibrosis in patients with chronic
      liver damage secondary to hepatitis C infection. Data reviewed included results
      of the in vitro effects of interferon on hepatic cell line cultures with regards
      to indirect markers of fibrosis, activation of hepatic stellate cells and
      oxidative stress response. In the clinical arena, there is current clear evidence
      of a favorable histological outcome in patients with sustained viral response to
      interferon therapy. For this reason, the current review focuses more on the
      histological outcomes regarding liver fibrosis in patients who have not attained
      viral response to therapy (non-responders) or who already have biopsy defined
      cirrhosis. Data in these patients were analyzed according to the results of
      objective testing of fibrosis through the assessment of liver biopsy and its
      change during time, specially because the morbidity and mortality of this disease
      is directly related to the complications of liver cirrhosis and not necessarily
      to the persistence of the hepatitis C virus. Lastly, it is concluded that the
      process of liver fibrosis/cirrhosis is a dynamic one and that there is some
      evidence to support the usefulness of interferon alpha therapy as a means to halt
      or retard the progression of hepatic fibrosis. The result of current clinical
      trials in which interferon therapy is being used to modify the progression of
      fibrosis in non-responders or cirrhotic patients is eagerly awaited.

PMID- 14702939
TI  - A simplified approach to implant dentistry with mini dental implants.

PMID- 14702940
TI  - Genetic and molecular regulation of bone regeneration.

PMID- 14702941
TI  - Everything you already know about being the best. So why aren't you?

PMID- 14702942
TI  - The first medical book in Yiddish: its dental writings.

PMID- 14702943
TI  - The use of triclosan in supportive treatment of gingivitis and periodontitis.

PMID- 14702944
TI  - Laser curettage--questionable value.

PMID- 14702945
TI  - A five-year evaluation of implants placed in extraction sockets.
AB  - The aim of this study is to examine extraction socket implant longevity and peri
      implant conditions longitudinally and to compare the outcome with implants placed
      in intact alveolar bone sites (nonextraction sites) after a time period in
      function of five years or more. We hypothesize that implants placed into fresh
      extraction sockets have a long-term rate of success similar to that of
      conventionally placed implants. Eleven extraction socket implants in eight
      patients with a follow-up of at least five years were included in this report.
      The implants were loaded with either single-tooth replacements or three-to-four
      unit fixed partial dentures after healing times of four to six months. Intraoral
      radiographs of the 11 implants were obtained immediately after surgery and upon
      recall five to seven years after surgery. In addition, the following clinical
      parameters were evaluated at each implant site five to seven years postsurgery:
      plaque indices (PT), bleeding indices (BI), probing depths, attachment level
      (AL), and distance from implant shoulder to mucosal margin (DIM). As a control,
      11 implants from a previous long-term study of nonsubmerged implants placed into
      intact alveolar bone sites by the same clinician were matched by implant
      location, sex, and age. Initial and long-term follow-up radiographs of the
      experimental and control groups were scanned into a computer. A computer program
      designed for radiographic implant analysis was utilized to examine the changes in
      radiographic bone levels over time in the two groups. After a period of five to
      seven years, the mean bone loss for the immediate implant group was 0.167 mm,
      while that of the control group was 0.460 mm. An unpaired t-test resulted in a P
      value = 0.0563, indicating that the mean change in bone levels between the two
      groups is not statistically significant. In addition, clinical evaluation
      parameters (PI, BI, AL, DIM) revealed no significant difference between the two
      groups. Therefore, it can be stated that in this study the long-term success rate
      for extraction socket implants is similar to that of conventionally placed
      implants.

PMID- 14702946
TI  - The effect of mobility on tooth prognosis and wound healing.

PMID- 14702947
TI  - Preservative and antibiotic toxicity to the ocular surface.

PMID- 14702948
TI  - Neuromuscular disorders: gene location.

PMID- 14702949
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 14702950
TI  - Congenital myasthenic syndromes: gene mutations.

PMID- 14702951
TI  - [Clinico-pathologic conference. Chronic granuloma of the face and
      sporotrichosis].

PMID- 14702952
TI  - The search for new global health entrepeneurs.

PMID- 14702953
TI  - Taming the double-edged sword.

PMID- 14702954
TI  - European Initiative to provide Africa with control of therapeutic development.

PMID- 14702955
TI  - Canada to allow production of generic AIDS drugs.

PMID- 14702956
TI  - Biologics for psoriasis.

PMID- 14702957
TI  - Atazanavir sulphate.

PMID- 14702958
TI  - Meniere disease patient information and support: which website?
AB  - Management of Meniere's disease remains problematic. Many different therapies are
      available, with variable success. Meniere's patients frequently research the
      Internet for information about the disease and to make contact with other
      patients. Internet websites providing this information have grown in number
      vastly in the past few years. This paper aims to identify the best websites
      available for Meniere's patients. Using Internet search engines the top 50
      websites were evaluated a Website Global Scoring and Evaluation Proforma. From
      the above the top ranking 15 websites were identified.

PMID- 14702959
TI  - Celebrating the physician-scientist.

PMID- 14702960
TI  - Presentation of the Kober Medal to Leon Rosenberg.

PMID- 14702961
TI  - Acceptance of the Kober Medal.

PMID- 14702962
TI  - 1998 ASCI Presidential Address.

PMID- 14702963
TI  - [For better health research: biological banks].

PMID- 14702964
TI  - [Life picture].

PMID- 14702965
TI  - Nerve agent toxicology.

PMID- 14702966
TI  - Giving old goats their due.

PMID- 14702967
TI  - Hand-assisted laparoscopic hepatectomy after partial splenic embolization.
AB  - The case of a patient with hepatocellular carcinoma and thrombocytopenia
      secondary to liver cirrhosis who underwent successful hand-assisted laparoscopic
      hepatectomy after partial splenic embolization is described. A 67-year-old man
      with severe liver cirrhosis was admitted for treatment of hepatocellular
      carcinoma. His early phase of hepatic angiography showed two hypervascular tumors
      in segment 6. The patients liver function was poor, with the indocyanine green
      retention at 15 min of 49.5%, a total serum bilirubin concentration of 2.0 mg/dl,
      an albumin concentration of 2.8 g/dl, and an hyaluronic acid concentration of 649
      ng/ml. The platelet count was 3.0 x 10(4)/microl secondary to hypersplenism.
      Partial splenic embolization decreased the splenic volume by 50% preoperatively.
      At 2 months later, the platelet count was 6.0 x 10(4)/microl, and hand-assisted
      laparoscopic partial hepatectomy was performed uneventfully. The patients
      postoperative course was unremarkable, and he was discharged on postoperative day
      12.

PMID- 14702968
TI  - Laparoscopic cholecystectomy for gallbladder lymphangiomas.
AB  - Intraabdominal lymphangiomas are rare benign tumors that can be difficult to
      diagnose preoperatively. The clinical presentation of these tumors is variable
      and potentially misleading. Therefore, complex imaging studies are required to
      evaluate this condition. Ultrasound and CT scan are important to make the correct
      preoperative diagnosis and also provide important information regarding location,
      size, and adjacent organ involvement. The treatment of choice is complete
      excision. This report describes two patients with cystic lymphangiomas
      originating in the gallbladder. The correct diagnosis was made preoperatively in
      one patient, and both patients were treated successfully by laparoscopy.

PMID- 14702969
TI  - Laparoscopy in the diagnosis and management of a complicated paraovarian cyst.
AB  - Paraovarian cysts account for 10% of adnexal masses and are most common in the
      3rd and 4th decades of life. They vary from small asymptomatic lesions to larger
      cysts, which may undergo hemorrhage or torsion. Children are rarely affected, and
      the diagnosis--particularly if pain presents in the right lower quadrant--may be
      difficult because the differentials diagnosis is wide. We report the case of a
      child who presented with a complicated paraovarian cyst. Laparoscopy enabled
      immediate diagnosis and appropriate management. We discuss the role of
      laparoscopy and the value of the Harmonic Scalpel in the management of these rare
      cysts.

PMID- 14702970
TI  - Penetrating chest gunshot wounds: conservative treatment.
AB  - Gunshot wounds, and in particular chest gunshot wounds, are becoming a growing
      problem in daily practice at many hospitals. Many authors propose a conservative
      attitude in certain cases. We present a patient with a chest gunshot wound
      successfully solved under conservative means and videothoracoscopic removal of
      the bullet.

PMID- 14702971
TI  - Pyogenic cholangitis after inadvertent submucosal contrast injection in the
      papilla of Vater in a patient with cholestatic hepatitis.
AB  - Common bile duct stones and tumors constitute the leading cause of acute biliary
      tract obstruction and cholangitis. Septic complications after diagnostic
      endoscopic retrograde cholangiopancreatography (ERCP) are very unusual in
      unobstructed bile ducts. There are only three reported cases of patients without
      evidence of biliary tract disease who developed cholangitis and liver abscesses
      due to Pseudomonas aeruginosa. Biliary endoscopists believe that the inadvertent
      submucosal injection of contrast into the papilla of Vater is an innocent
      accident that has no serious consequences other than increasing the percentage of
      unsuccessful catheterizations of the common bile duct. Herein we describe a
      patient with drug-induced cholestatic hepatitis who developed pyogenic
      cholangitis after the inadvertent injection of submucosal contrast in the papilla
      of Vater.

PMID- 14702972
TI  - Subcutaneous emphysema after associated colonoscopy and transanal excision of
      rectal adenoma.
AB  - Non-traumatic subcutaneous emphysema (NSE) is a rare complication of procedures
      of the digestive tract. To the best of our knowledge, it has never been reported
      to occur after transanal surgery. Herein we present the first known case of NSE
      accompanied by retropneumoperitoneum and pneumomediastinum to develop after
      colonoscopy and full-thickness transanal removal of a rectal polyp.

PMID- 14702973
TI  - Colonoscopically placed hemoclips as treatment for massive appendiceal stump
      bleeding.
AB  - Massive bleeding from an appendiceal stump is a rare but occasionally seen severe
      complication. The bleeding may drain into the abdominal cavity, the
      retroperitoneum, or the digestive tract. Gastrointestinal hemorrhage may occur
      early or even years after appendectomy. The typical management includes ligation
      of the bleeding vessel or cecal resection done by either emergency laparotomy or
      laparoscopy. An alternative treatment option would be an angiographic
      embolization of the bleeding vessel. We report on a 33-year-old woman with severe
      lower gastrointestinal hemorrhage 1 day after an apparently uncomplicated
      appendectomy for acute phlegmonous appendicitis with ligation and invagination of
      the appendiceal stump. Hemoglobin level dropped to 6.3 g/dl and made blood
      transfusion necessary. The cause of bleeding was a small intramural branch of the
      appendiceal artery at the appendiceal stump, which was diagnosed by emergency
      colonoscopy. The hemorrhage could be controlled endoscopically by placing
      hemoclips on the distinct vessel in combination with a biological tissue
      adhesive. The patient recovered thereafter without further intervention.
      Endoscopic clipping for the treatment of appendiceal stump bleeding is a novel,
      effective, and safe procedure. Thereby, conventional emergency laparotomy or
      laparoscopy or angiographic embolization can be avoided.

PMID- 14702974
TI  - Recurrent small bowel obstruction after laparoscopic surgery for gallstone ileus.
AB  - Gallstone ileus is an uncommon cause of small bowel obstruction. A patient
      presenting with gallstone ileus was managed in our department by laparoscopic
      enterolithotomy. Postoperatively, the patient developed recurrent small bowel
      obstruction due to the presence of a second gallstone. It is therefore important
      to exclude the possibility of multiple gallstones at the initial operation.

PMID- 14702975
TI  - Laparoscopic surgery and ergonomics: it's time to think of ourselves as well.

PMID- 14702976
TI  - Management of peritoneal tear during endoscopic extraperitoneal inguinal
      hernioplasty.

PMID- 14702977
TI  - Diabetologia 1998-2003 changing of the guard.

PMID- 14702978
TI  - Laparoscopic ventral hernia repair.

PMID- 14702979
TI  - Health promoting community design.

PMID- 14702980
TI  - Fracture characteristics of acrylic bone cement-bone composites.
AB  - In this study, the fracture properties of Perspex, acrylic bone cement prepared
      using a commercially available reduced pressure mixing system and a bone cement
      bone composite were compared under different test conditions. The method used was
      the double-torsion (DT) test. The observations made from this investigation are
      as follows. The fracture toughness and critical crack length for Perspex
      significantly increased (ANOVA, p = 0.001) when tested in water compared to air.
      An increase in test temperature from 19 to 37 degrees C resulted in a decrease in
      the fracture properties in water, this reduction being also statistically
      significant (ANOVA, p = 0.02). The mean fracture toughness and standard deviation
      of CMW3 bone cement when mixed under reduced pressure was 2.19 +/- 0.11 MN m(
      3/2) compared to 3.89 +/- 0.10 MN m(-3/2) for the cement-bone composite (ANOVA, p
      = 0.004). The crack length determined for CMW3 bone cement and the cement bone
      composite were 0.323 +/- 0.031 and 1.1434 +/- 0.61 mm respectively. The plateau
      loads of the composite material were higher than measured for the monolithic
      acrylic bone cement, 249.66 +/- 67.75 N compared with 140.83 +/- 6.82 N. The high
      level of variation recorded for the plateau loads of the bone cement bone
      composite is due to the orientation and volume fraction of the cancellous bone.
      It can be concluded from this investigation that acrylic bone cement
      interdigitation into the cancellous bone results in a superior material with
      respect to crack resistance in comparison with the bone cement as a lone entity.
      Therefore it is an advantage if there is sufficient cancellous bone stock
      available within the intermedullary canal to allow bone cement penetration to
      occur, for the transfer of loads during daily activity. Additionally, it is
      paramount that the clinician ensures that adequate pressure is applied and
      maintained for an appropriate time during cement injection and prosthesis
      insertion in order to ensure optimum cement penetration into the pore openings of
      the cancellous bone, thus improving the resistance of the cement mantle to
      fracture and ultimately improving the longevity of the joint replacement.

PMID- 14702981
TI  - Microbubble ultrasound contrast agents: a review.
AB  - The superior scattering properties of gas bubbles compared with blood cells have
      made microbubble ultrasound contrast agents important tools in ultrasound
      diagnosis. Over the past 2 years they have become the focus of a wide and rapidly
      expanding field of research, with their benefits being repeatedly demonstrated,
      both in ultrasound image enhancement, and more recently in drug and gene delivery
      applications. However, despite considerable investigation, their behaviour is by
      no means fully understood and, while no definite evidence of harmful effects has
      been obtained, there remain some concerns as to their safety. In this review the
      existing theoretical and experimental evidence is examined in order to clarify
      the extent to which contrast agents are currently understood and to identify
      areas for future research. In particular the disparity between the conditions
      considered in theoretical models and those encountered both in vitro, and more
      importantly in vivo is discussed, together with the controversy regarding the
      risk of harmful bio-effects.

PMID- 14702982
TI  - A technique for the measurement of patellar tracking during weight-bearing
      activities using ultrasound.
AB  - A new fixation device, the femoral clamp, was developed in this study for the
      ultrasound measurement of patellar medio-lateral motion during sitting and
      squatting knee flexion/extension. Seventeen subjects, 6 males, 11 females, aged
      between 18 and 40 years were recruited for the test. Results showed that the
      patella moved medially then laterally from extension to flexion when sitting.
      Weight-bearing knee motion produced a more laterally tracked patella without the
      presence of the initial medial patellar translation. The tracking patterns of the
      patellae were similar regardless of knee movement direction. The patellar lateral
      position was greatly affected by the movement task (p < 0.0005), and was also
      influenced by gender for maximum medial position (p < 0.05). The reproducibility
      of the measurement was between 0.29 and 0.90 for the intra-rater and 0.34-0.75
      for the inter-rater reliability. The accuracy of the ultrasound measurement was
      validated by interventional magnetic resonance (iMR) imaging of the patella and
      the mean error of the measurement was 1.4 +/- 3.2 mm. Although further research
      is needed to improve the accuracy and reliability of this method, it has
      demonstrated the feasibility of obtaining patellar tracking data during load
      bearing activities.

PMID- 14702983
TI  - Medical device regulation for manufacturers.
AB  - Manufacturers of medical devices are held to a higher standard than manufacturers
      of many other products due to the potential severity of the consequences of
      introducing inferior or unsafe products to the market-place. In Canada, the
      medical device industry is regulated by Health Canada under the Medical Device
      Regulations of the Food and Drug Act. The Medical Device Regulations define
      requirements of medical device design, development and manufacture to ensure that
      products reaching the public are safe and effective. Health Canada also requires
      that medical device manufacturers maintain distribution records to ensure that
      devices can be traced to the source and consumers can be contacted successfully
      in the event that a device is recalled. Medical devices exported from Canada must
      be compliant with the regulations of the country of import. The Canadian Medical
      Device Regulations were based on the Medical Device Directives of the European
      Union thus facilitating approval of Canadian devices for the European market. The
      United States Food and Drug Administration has separate and distinct requirements
      for safety and quality of medical devices. While effort has been made to
      facilitate approval and trade of Canadian medical devices in the United States
      and the European Union, obtaining approval from multiple regulatory bodies can
      result in increased device development time and cost. The Global Harmonization
      Task Force is an organization composed of members from Japanese, Australian,
      European, Canadian and American medical device regulatory bodies. This
      organization was formed with the objective of harmonizing medical device
      regulations in an effort to facilitate international trade and standardize the
      quality of medical devices available to all countries. This paper discusses the
      requirements that must be met by manufacturers when designing and manufacturing
      medical devices.

PMID- 14702984
TI  - Rapid manufacturing techniques in the development of an axial blood pump
      impeller.
AB  - This paper presents a comparison of manufacturing techniques used in the
      development of an axial blood pump impeller. In this development process the
      impeller was designed and its performance was evaluated with the aid of
      computational fluid dynamics (CFD). Prototypes of those designs where the CFD
      results show promise were needed in sufficient quantities at a low cost for
      experimental validation of the CFD results. As the impeller is less than 16 mm in
      diameter with a maximum blade thickness of about 1.5 mm, innovative manufacturing
      techniques are explored in this paper to determine the best process for quick
      fabrication of prototypes that are dimensionally accurate, structurally robust
      and low in cost. Four rapid prototyping techniques were explored. The completed
      parts were compared on the basis of manufacturing time, quality and strength of
      parts obtained, manufacturing cost and also in vitro performances. Based on these
      studies, it was concluded that selective laser sintering (SLS) is the most
      appropriate method for the quick production of prototype parts for evaluation of
      pump performance.

PMID- 14702985
TI  - Microscopic asperity contact and deformation of ultrahigh molecular weight
      polyethylene bearing surfaces.
AB  - The effect of the roughness and topography of ultrahigh molecular weight
      polyethylene (UHMWPE) bearing surfaces on the microscopic contact mechanics with
      a metallic counterface was investigated in the present study. Both simple
      sinusoidal roughness forms, with a wide range of amplitudes and wavelengths, and
      real surface topographies, measured before and after wear testing in a simple pin
      on-plate machine, were considered in the theoretical analysis. The finite
      difference method was used to solve the microscopic contact between the rough
      UHMWPE bearing surface and a smooth hard counterface. The fast Fourier transform
      (FFT) was used to cope with the large number of mesh points required to represent
      the surface topography of the UHMWPE bearing surface. It was found that only
      isolated asperity contacts occurred under physiological loading, and the real
      contact area was only a small fraction of the nominal contact area. Consequently,
      the average contact pressure experienced at the articulating surfaces was
      significantly higher than the nominal contact pressure. Furthermore, it was shown
      that the majority of asperities on the worn UHMWPE pin were deformed in the
      elastic region, and consideration of the plastic deformation only resulted in a
      negligible increase in the predicted asperity contact area. Microscopic asperity
      contact and deformation mechanisms may play an important role in the
      understanding of the wear mechanisms of UHMWPE bearing surfaces.

PMID- 14702986
TI  - Computer simulation of the human leg subjected to impact loading.
AB  - One of the most important tasks in clinical practice is to determine accurately
      the forces and displacements of the various anatomical structural components of
      the human leg, especially when subjected to impact loading. This paper therefore
      develops a computer simulation which describes the biodynamic response of the
      human lower extremity for realistic activities such as kicking by foot etc.
      Firstly, the paper derives the nonlinear equations of motion and nonlinear
      constraint equation governing the sagittal plane response of the human leg
      subjected to impact loading. The equations are then solved using numerical
      techniques and the results are presented. Special attention is given to the
      ligament, contact and muscle group forces, the location of contact points,
      anterior-posterior displacements and the motion trajectories of the femur and the
      tibia.

PMID- 14702987
TI  - Apparatus to test insertion and removal torque of bone screws.
AB  - This paper describes affordable equipment for testing bone screw torque,
      corresponding to ASTM standard F543-00 for testing metallic medical bone screws.
      Correct testing of thin and long bone screws is essential due to screw failures
      during insertion and removal of the screws. Furthermore, insertion torque is an
      important factor in predicting fixation strength, screw pull-out force and
      effects of surface treatment of screws. The capability of the custom-built tester
      was determined using polytetrafluoroethylene and wood disc samples and bone
      screws. Bovine cortical bones allowed testing to the failure limit, i.e. the
      torque increased in long screws to the fracture limit. For 2.7 and 3.5 mm thick
      self-tapping cortical bone screws, the failure torques were 30-50 per cent higher
      than the minimum values required by the standard (1.0 and 2.3 N m respectively).
      The equipment provided reproducible results and fulfilled the ASTM standard very
      well. Preliminary testing with amorphous diamond coated bone screws showed good
      durability of the coating and on average 10-15 per cent lower torque values
      compared with uncoated screws. The equipment can be used to measure insertion and
      removal torques as described in the standard. Furthermore, it also allows testing
      of normal screws and bolts.

PMID- 14702988
TI  - The vigilance decrement reflects limitations in effortful attention, not
      mindlessness.
AB  - Robertson, Manly, Andrade, Baddeley, and Yiend (1997) proposed that the decline
      in performance efficiency over time in vigilance tasks (the vigilance decrement)
      is characterized by "mindlessness" or a withdrawal of attentional effort from the
      monitoring assignment. We assessed that proposal using measures of perceived
      mental workload (NASA-TLX) and stress (Dundee Stress State Questionnaire). Two
      types of vigilance task were employed: a traditional version, wherein observers
      made button-press responses to signify detection of rarely occurring critical
      signals, and a modified version, developed by Robertson et al. to promote
      mindlessness via routinization, wherein button-press responses acknowledged
      frequently occurring neutral stimulus events and response withholding signified
      critical signal detection. The vigilance decrement was observed in both tasks,
      and both tasks generated equally elevated levels of workload and stress, the
      latter including cognitions relating to performance adequacy. Vigilance
      performance seems better characterized by effortful attention (mindfulness) than
      by mindlessness. Actual or potential applications of this research include
      procedures to reduce the information-processing demand imposed by vigilance tasks
      and the stress associated with such tasks.

PMID- 14702989
TI  - Attentional models of multitask pilot performance using advanced display
      technology.
AB  - In the first part of the reported research, 12 instrument-rated pilots flew a
      high-fidelity simulation, in which air traffic control presentation of auditory
      (voice) information regarding traffic and flight parameters was compared with
      advanced display technology presentation of equivalent information regarding
      traffic (cockpit display of traffic information) and flight parameters (data link
      display). Redundant combinations were also examined while pilots flew the
      aircraft simulation, monitored for outside traffic, and read back communications
      messages. The data suggested a modest cost for visual presentation over auditory
      presentation, a cost mediated by head-down visual scanning, and no benefit for
      redundant presentation. The effects in Part 1 were modeled by multiple-resource
      and preemption models of divided attention. In the second part of the research,
      visual scanning in all conditions was fit by an expected value model of selective
      attention derived from a previous experiment. This model accounted for 94% of the
      variance in the scanning data and 90% of the variance in a second validation
      experiment. Actual or potential applications of this research include guidance on
      choosing the appropriate modality for presenting in-cockpit information and
      understanding task strategies induced by introducing new aviation technology.

PMID- 14702990
TI  - Operator functional state classification using multiple psychophysiological
      features in an air traffic control task.
AB  - We studied 2 classifiers to determine their ability to discriminate among 4
      levels of mental workload during a simulated air traffic control task using
      psychophysiological measures. Data from 7 air traffic controllers were used to
      train and test artificial neural network and stepwise discriminant classifiers.
      Very high levels of classification accuracy were achieved by both classifiers.
      When the 2 task difficulty manipulations were tested separately, the percentage
      correct classifications were between 84% and 88%. Feature reduction using
      saliency analysis for the artificial neural networks resulted in a mean of 90%
      correct classification accuracy. Considering the data as a 2-class problem,
      acceptable load versus overload, resulted in almost perfect classification
      accuracies, with mean percentage correct of 98%. In applied situations, the most
      important distinction among operator functional states would be to detect mental
      overload situations. These results suggest that psychophysiological data are
      capable of such discriminations with high levels of accuracy. Potential
      applications of this research include test and evaluation of new and modified
      systems and adaptive aiding.

PMID- 14702991
TI  - Head up versus head down: the costs of imprecision, unreliability, and visual
      clutter on cue effectiveness for display signaling.
AB  - We conducted 2 experiments to investigate the clutter-scan trade-off between the
      cost of increasing clutter by overlaying complex information onto the forward
      field of view using a helmet-mounted display (HMD) and the cost of scanning when
      presenting this information on a handheld display. In the first experiment, this
      trade-off was examined in terms of the spatial accuracy of target cuing data in a
      relatively sparse display; in the second, the spatial accuracy of the cue was
      varied more radically in an information-rich display. Participants were asked to
      detect and identify targets hidden in the far domain while performing a
      monitoring task in the near domain using either an HMD or a handheld display. The
      results revealed that on a sparse display, the reduced scanning from the HMD
      presentation of cuing out-weighed the costs of clutter for cued targets,
      regardless of cue precision, but no benefit was found for uncued targets. When
      the HMD displayed task-irrelevant information, however, target detection was
      hindered by the extraneous clutter in the forward field of view relative to the
      handheld display condition, and this cost of clutter increased as the amount of
      data that needed to be inspected increased. Potential applications of this
      research include the development of design considerations for head-up displays
      for aviation and military applications.

PMID- 14702992
TI  - Comparing statistical and machine learning classifiers: alternatives for
      predictive modeling in human factors research.
AB  - Multivariate classification models play an increasingly important role in human
      factors research. In the past, these models have been based primarily on
      discriminant analysis and logistic regression. Models developed from machine
      learning research offer the human factors professional a viable alternative to
      these traditional statistical classification methods. To illustrate this point,
      two machine learning approaches--genetic programming and decision tree induction-
      were used to construct classification models designed to predict whether or not a
      student truck driver would pass his or her commercial driver license (CDL)
      examination. The models were developed and validated using the curriculum scores
      and CDL exam performances of 37 student truck drivers who had completed a 320-hr
      driver training course. Results indicated that the machine learning
      classification models were superior to discriminant analysis and logistic
      regression in terms of predictive accuracy. Actual or potential applications of
      this research include the creation of models that more accurately predict human
      performance outcomes.

PMID- 14702993
TI  - Spatial orientation in 3-D desktop displays: using rooms for organizing
      information.
AB  - Understanding how spatial knowledge is acquired is important for spatial
      navigation and for improving the design of 3-D perspective interfaces. Configural
      spatial knowledge of object locations inside rooms is learned rapidly and easily
      (Colle & Reid, 1998), possibly because rooms afford local viewing in which
      objects are directly viewed or, alternatively, because of their structural
      features. The local viewing hypothesis predicts that the layout of objects
      outside of rooms also should be rapidly acquired when walls are removed and rooms
      are sufficiently close that participants can directly view and identify objects.
      It was evaluated using pointing and sketch map measures of configural knowledge
      with and without walls by varying distance, lighting levels, and observation
      instructions. Although within-room spatial knowledge was uniformly good, local
      viewing was not sufficient for improving spatial knowledge of objects in
      different rooms. Implications for navigation and 3-D interface design are
      discussed. Actual or potential applications of this research include the design
      of user interfaces, especially interfaces with 3-D displays.

PMID- 14702994
TI  - Effects of deliberate practice on crisis decision performance.
AB  - This study examined the impact of deliberate practice on pilot decision making in
      once-in-a-career crisis decision scenarios. First we explored the impact of
      deliberate practice on pilot decision-making performance for crisis flying
      scenarios that had been practiced in their entirety. Then we looked at the impact
      of deliberate practice in which one aspect of the crisis scenario--the particular
      malfunction--was unpracticed. We analyzed pilot decision-making performance in
      response to 160 airborne mechanical malfunctions. We initially found that
      deliberate practice significantly improves decision-making performance for wholly
      practiced crises but does not improve decision-making performance when the
      specific malfunction has not been practiced. We then split decision making for
      each crisis into two phases: assessment and action selection. For wholly
      practiced crisis scenarios, additional deliberate practice positively impacts
      each decision-making phase. However, for part-practiced scenarios, deliberate
      practice appears to differentially affect phase of error. Specifically, pilots
      with more deliberate practice erred in action selection, whereas less-practiced
      pilots erred in assessment. Actual or potential applications of this research
      include training proscriptions for crisis decision making.

PMID- 14702995
TI  - The effect of gesture on speech production and comprehension.
AB  - Hand gestures are ubiquitous in communication. However, there is considerable
      debate regarding the fundamental role that gesture plays in communication and,
      subsequently, regarding the value of gesture for telecommunications. Controversy
      exists regarding whether gesture has a primarily communicative function
      (enhancing listener comprehension) or a primarily noncommunicative function
      (enhancing speech production). Moreover, some have argued that gesture seems to
      enhance listener comprehension only because of the effect gesture has on speech
      production. The purpose of this study was to examine the extent to which gesture
      enhances listener comprehension and the extent to which the effect of gesture on
      listener comprehension is mediated by the effects of gesture on speech
      production. Results indicated that gesture enhanced both listener comprehension
      and speech production. When the effects of gesture on speech production were
      controlled, the relationship between gesture and listener comprehension was
      reduced but still remained significant. These results suggest that gesture aids
      the listener as well as the speaker and that gesture has a direct effect on
      listener comprehension, independent of the effects gesture has on speech
      production. Implications for understanding the value of gestural information in
      telecommunications are discussed. Potential applications of this research include
      the design of computer-mediated communication systems and displays in which the
      visibility of gestures may be beneficial.

PMID- 14702996
TI  - Determining the effectiveness of the usability problem inspector: a theory-based
      model and tool for finding usability problems.
AB  - Despite the increased focus on usability and on the processes and methods used to
      increase usability, a substantial amount of software is unusable and poorly
      designed. Much of this is attributable to the lack of cost-effective usability
      evaluation tools that provide an interaction-based framework for identifying
      problems. We developed the user action framework and a corresponding evaluation
      tool, the usability problem inspector (UPI), to help organize usability concepts
      and issues into a knowledge base. We conducted a comprehensive comparison study
      to determine if our theory-based framework and tool could be effectively used to
      find important usability problems in an interface design, relative to two other
      established inspection methods (heuristic evaluation and cognitive walkthrough).
      Results showed that the UPI scored higher than heuristic evaluation in terms of
      thoroughness, validity, and effectiveness and was consistent with cognitive
      walkthrough for these same measures. We also discuss other potential advantages
      of the UPI over heuristic evaluation and cognitive walkthrough when applied in
      practice. Potential applications of this work include a cost-effective
      alternative or supplement to lab-based formative usability evaluation during any
      stage of development.

PMID- 14702997
TI  - The impact of mental fatigue on exploration in a complex computer task: rigidity
      and loss of systematic strategies.
AB  - We investigated the impact of mental fatigue on exploration in a complex computer
      task. The exploration behavior of participants who underwent a fatigue
      manipulation (N = 36) was compared with that of a control (nonfatigued) group (N
      = 32). A distinction was also made between participants with high or low levels
      of general computer experience. Results showed that fatigued participants used
      significantly less systematic exploration and made more errors than did
      nonfatigued participants. Fatigued participants with low computer experience also
      showed significantly more rigid behavior than did the other participants. No
      differences were found on the number of subtasks solved. Compared with low
      experience participants, highly experienced participants showed significantly
      more systematic exploration, less unsystematic trial and error, solved more
      subtasks, and made fewer errors (marginally significant p = .056). Findings were
      interpreted as the result of reduced task engagement under fatigue and reduced
      involvement of executive control on behavior. Actual or potential applications of
      this research include guidelines to prevent detrimental effects of mental fatigue
      on exploration behavior.

PMID- 14702998
TI  - Traffic signal color recognition is a problem for both protan and deutan color
      vision deficients.
AB  - We investigated the effect of color-vision deficiency on reaction times and
      accuracy of identification of traffic light signals. Participants were 20 color
      normal and 49 color-deficient males, the latter divided into subgroups of
      different severity and type. Participants performed a tracking task. At random
      intervals, stimuli simulating standard traffic light signals were presented
      against a white background at 5 degrees to right or left. Participants identified
      stimulus color (red/yellow/green) by pressing an appropriate response button.
      Mean response times for color normals were 525, 410, and 450 ms for red, yellow,
      and green lights, respectively. For color deficients, response times to red
      lights increased with increase in severity of color deficiency, with deutans
      performing worse than protans of similar severity: response times of deuteranopes
      and protanopes were 53% and 35% longer than those of color normals. A similar
      pattern occurred for yellow lights, with deuteranopes and protanopes having
      increased response times of 85% and 53%, respectively. For green lights, response
      times of all groups were similar. Error rates showed patterns similar to those of
      response times. Contrary to previous studies, deutans performed much worse than
      protans of similar severity. Actual or potential applications of this research
      include traffic signal design and driver licensing.

PMID- 14702999
TI  - What to expect from immersive virtual environment exposure: influences of gender,
      body mass index, and past experience.
AB  - For those interested in using head-coupled PC-based immersive virtual environment
      (VE) technology to train, entertain, or inform, it is essential to understand the
      effects this technology has on its users. This study investigated potential
      adverse effects, including the sickness associated with exposure and extreme
      responses (emesis, flashbacks). Participants were exposed to a VE for 15 to 60
      min, with either complete or streamlined navigational control and simple or
      complex scenes, after which time measures of sickness were obtained. More than
      80% of participants experienced nausea, oculomotor disturbances, and/or
      disorientation, with disorientation potentially lasting > 24 hr. Of the
      participants, 12.9% prematurely ended their exposure because of adverse effects;
      of these, 9.2% experienced an emetic response, whereas only 1.2% of all
      participants experienced emesis. The results indicate that designers may be able
      to reduce these rates by limiting exposure duration and reducing the degrees of
      freedom of the user's navigational control. Results from gender, body mass, and
      past experience comparisons indicated it may be possible to identify those who
      will experience adverse effects attributable to exposure and warn such
      individuals. Applications for this research include military, entertainment, and
      any other interactive systems for which designers seek to avoid adverse effects
      associated with exposure.

PMID- 14703000
TI  - Aging and osteoarthritis.

PMID- 14703001
TI  - Epidemiology of osteoarthritis: prevalence, risk factors and functional impact.
AB  - Osteoarthritis (OA), the most common form of arthritis, is a major contributor to
      functional impairment and reduced independence in older adults. OA of the hip and
      knee are two of the most important causes of pain and physical disability in
      community-dwelling adults. Symptomatic hand OA is a common disease among the
      elderly, and impairs hand function, this impairment being largely mediated by
      pain. Like other chronic diseases, the etiology of OA is multifactorial, and
      several local and systemic risk factors have been identified. Differences in the
      prevalence of OA may be attributable to both genetic and life-style factors.
      Disease definition may be based upon clinical or radiographic criteria, although
      case definition should rely on radiographic features for epidemiological studies.
      This review focuses on the functional impact of the disease, describes geographic
      differences in prevalence rates, discusses disease definition criteria, and
      summarizes the most common risk factors, including age, associated with the risk
      of OA.

PMID- 14703002
TI  - The pathophysiology of osteoarthritis.
AB  - Osteoarthritis (OA) is a complex disease whose pathogenesis includes the
      contribution of biomechanical and metabolic factors which, altering the tissue
      homeostasis of articular cartilage and subchondral bone, determine the
      predominance of destructive over productive processes. A key role in the
      pathophysiology of articular cartilage is played by cell/extra-cellular matrix
      (ECM) interactions, which are mediated by cell surface integrins. In a
      physiologic setting, integrins modulate cell/ECM signaling, essential for
      regulating growth and differentiation and maintaining cartilage homeostasis.
      During OA, abnormal integrin expression alters cell/ECM signaling and modifies
      chondrocyte synthesis, with the following imbalance of destructive cytokines over
      regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate
      the enzymatic degradation of cartilage matrix and are not counterbalanced by
      adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are
      metalloproteinases (MMPs), which are sequentially activated by an amplifying
      cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs
      (TIMPs), whose synthesis is low compared with MMP production in OA cartilage.
      Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and
      others, which do not simply repair the tissue damage induced by catabolic
      factors, but play an important role in OA pathogenesis.

PMID- 14703003
TI  - Laboratory investigations in osteoarthritis.
AB  - Progress in the knowledge of pathogenic mechanisms and a better definition of the
      disease, together with the availability of new technologies, have recently
      improved the value of laboratory investigations in osteoarthritis (OA). The main
      objectives of these findings are early diagnosis, assessment of disease activity
      and severity, and evaluation of therapeutic effects. In this context, biochemical
      markers are potentially useful, as they are non-invasive and non-expansive.
      However, among the numerous substances increasingly proposed for these purposes,
      very few may be considered as true disease markers in OA; COMP, antigenic keratan
      sulphate, hyaluronic acid, YKL-40, type III collagen N-propeptide and urinary
      glucosyl-galactosyl pyridinoline seem to be the most promising. However, serum or
      urinary determinations of these molecules are difficult to interpret adequately,
      due to their complex metabolism. Careful analysis of synovial fluid, mainly
      directed to leukocyte count and crystal detection, is still essential for
      diagnosis, but also for the evaluation of the levels of important markers of
      local inflammation, such as metalloproteinases and cytokines, which seem to be
      crucial in the pathogenesis of OA.

PMID- 14703004
TI  - Clinical and radiological evaluation of hip, knee and hand osteoarthritis.
AB  - Evaluation of hip, knee and hand osteoarthritis (OA) involves clinical and
      radiological outcome measures. Clinical, mainly visual analog scale (VAS) for
      pain, algofunctional or Lequesne's indices for hip and knee OA, Western Ontario
      and Mac Master Universities OA Index (WOMAC) for hip and knee OA, Dreiser's
      functional index for hand OA and some quality-of-life (QoL) indices are presented
      and discussed. Their utility is considered according to various uses: assessment
      of OA severity and course in therapeutic trials, in daily practice, as a help for
      surgical decision, and with regard to QoL as instruments for establishing the
      place of OA among differing chronic rheumatic conditions. Radiological assessment
      methods, especially for potential structure-modifying drug trials, mainly involve
      either manual measurement of joint space narrowing on radiographs over a period
      of several years, or measurement on X-ray digitized images. Last but not least,
      to conclude this review, we propose a selection of the most rapid and practical
      instruments allowing OA assessment in daily practice, with appropriate comments.

PMID- 14703005
TI  - Radiographic assessment of osteoarthritis: analysis of disease progression.
AB  - Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions
      affecting older adults, and is a significant public health problem among adults
      of working age. The knee is the most frequently involved joint site associated
      with disability in OA. Diagnosis of OA is primarily based on history and physical
      examination, but radiographic findings, including asymmetric joint space
      narrowing (JSN), subchondral sclerosis, osteophyte formation, subluxation, and
      distribution patterns of osteoarthritic changes are all helpful when diagnosis is
      uncertain. Structural morphological changes on X-rays are also considered the
      primary outcome variables for assessing the progression of OA. The development of
      new methods for prevention and treatment of OA requires improved understanding of
      the factors that influence its progression. The ability to assess progression
      quantitatively is a necessary first step in understanding factors that influence
      the disease process. Depending on the joint studied, several indices are
      currently used for assessing radiological progression of OA, including individual
      radiographic features (e.g., marginal osteophytes), composite indices (e.g.,
      Kellgren and Lawrence scoring systems), and quantitative measures (e.g., joint
      space width measurement). Unfortunately, the review of studies evaluating the
      longitudinal rate of JSN indicates that the yearly change may be very small and
      of doubtful clinical significance. This emphasizes the need for further
      refinement in the definition of radiographic outcomes in prospective clinical
      trials. This review focuses on the available scoring methods used for the sites
      most frequently involved in OA (hand, knee, hip) and their various advantages and
      disadvantages.

PMID- 14703006
TI  - The therapeutic approach to osteoarthritis.
AB  - Ideally, treatment is based on etiology, if possible on pathophysiology, and in
      practice on anatomical and clinical findings. A systematic search for the
      etiological factors of osteoarthritis (OA) shows that the various mechanisms are
      frequently associated. Etiological treatments are rare. We may mention acetabular
      tectoplasty in hip dysplasia with minimal joint space narrowing. Valgus osteotomy
      would also be indicated for early medial tibiofemoral OA in genu varum if we had
      definite proof that, if left untreated, this deformity inevitably leads to
      clinically severe OA. This is not the case. One of the limitations of this
      etiological treatment lies in the fact that we do not know which patients are at
      risk of developing painful OA. Instead, certain risk factors for OA are known, so
      that primary and secondary prevention of the disease is possible. While age, sex
      and genetic predisposition are not amenable to preventive action, the same does
      not apply to the following factors: obesity, sports, and occupational activity.
      Thanks to in vitro studies of cultured normal and osteoarthritic chondrocytes and
      to experimental models of OA in animals, the pathophysiological mechanisms of OA
      are beginning to be better known. The prospect thus arises of "therapeutic
      manipulations" of precise pharmacological targets, even if it is still too soon
      to speak of true pathophysiological treatment of this disease. For instance,
      various interventions along the IL-1 pathway can be envisaged and have all been
      tested in animals. In practice, treating OA means taking into consideration its
      various signs: pain which appears to be mechanical and more or less chronic,
      joint stiffness, instability, effusion, and--the consequence of these symptoms-
      the professional, social and personal handicap of the patient. The treatment of
      OA must be approached from a global perspective, associating whenever possible
      symptomatic treatment, disease-modifying treatment, education and rehabilitation.
      In other words, the treatment of OA requires an overall approach, associating
      pharmacological and non-pharmacological modalities.

PMID- 14703007
TI  - Bisphosphonates: potential therapeutic agents for disease modification in
      osteoarthritis.
AB  - Current treatments for osteoarthritis (OA) are mainly targeted towards providing
      short-term symptom relief. The focus in the development of disease-modifying
      drugs has been on therapies that modify cartilage directly. Recent research has
      highlighted the importance of subchondral bone as a target for therapeutic
      intervention and disease modification. At the subchondral level, affected joints
      have decreased bone mineral content and quality. In addition, increased bone
      turnover has been observed at levels similar to those in patients with
      osteoporosis. Consequently, the potential benefits of drugs that alter bone
      metabolism are being examined in this disease, in particular, the antiresorptive
      agents, bisphosphonates. Results from pre-clinical studies have shown promising
      results for these compounds. Although the mechanism of action remains unclear,
      comparative studies indicate that this activity may be unique to the specific
      structure of the bisphosphonate, rather than representative of a class effect.
      Clinical studies are now under way to determine the efficacy and safety of
      bisphosphonates which may offer new therapeutic options in the treatment of OA.

PMID- 14703008
TI  - Use of non-pharmacological therapies among patients with osteoarthritis.
AB  - BACKGROUND AND AIMS: Non-pharmacological therapies are an important component of
      treatment for osteoarthritis (OA), but they may be under-used. This study
      examined the prevalence of self-reported use of common non-pharmacological
      therapies, as well as patient and physician-related predictors of use. METHODS:
      Subjects included 205 veterans who completed a survey regarding OA symptoms and
      treatments. Analyses examined the prevalence of use of three specific non
      pharmacological therapies: exercise, physical therapy (PT), and dietary/herbal
      supplements. We also examined whether patient variables (demographics, clinical
      characteristics, and perceived helpfulness of non-pharmacological therapies) and
      physician characteristics (age, gender, race, and recommendation of non
      pharmacological therapies) were associated with use of each therapy. RESULTS:
      Forty-six percent of subjects reported current use of exercise, 11% reported
      using PT, and 12%, dietary/herbal supplements. Patient demographic and clinical
      characteristics were generally poor predictors of use of non-pharmacological
      therapy. However, females were more likely to report exercising than males
      (p<0.05), and patients with greater disease severity were more likely to report
      current use of PT (p<0.001). Patients' perceived helpfulness of each therapy
      significantly predicted use (p<0.05). Physician demographic characteristics were
      not strong predictors of patients' use of therapy, but physician recommendation
      for exercise and PT predicted patients' use (p<0.05). CONCLUSIONS: Among this
      sample of veterans with OA, there was relatively low use of exercise, PT, and
      dietary/herbal supplements. Patients' perceptions of treatment helpfulness and
      physician recommendations strongly predicted use. These results signal the
      importance of interventions aimed at educating both patients and physicians about
      these therapies.

PMID- 14703009
TI  - Osteoarthritis and osteoporosis: clinical and research evidence of inverse
      relationship.
AB  - The etiology of osteoporosis (OP) and osteoarthritis (OA) is multifactorial: both
      constitutional and environmental factors, ranging from genetic susceptibility,
      endocrine and metabolic status, to mechanical and traumatic injury, are thought
      to be involved. When interpreting research data, one must bear in mind that
      pathophysiologic factors, especially in disorders associated with aging, must be
      regarded as either primary or secondary. Therefore, findings in end-stage
      pathology are not necessarily the evidence or explanation of the primary cause or
      event in the diseased tissue. Both aspects of research are important for
      potentially curative or preventive measures. These considerations, in the case of
      our topic--the inverse relationship of OP and OA--are of particular importance.
      Although the inverse relationship between two frequent diseases associated with
      aging, OA and OP, has been observed and studied for more than 30 years, the topic
      remains controversial for some and stimulating for many. The anthropometric
      differences of patients suffering from OA compared with OP are well established.
      OA cases have stronger body build and are more obese. There is overwhelming
      evidence that OA cases have increased BMD or BMC at all sites. This increased BMD
      is related to high peak bone mass, as shown in mother-daughter and twin studies.
      With aging, the bone loss in OA is lower, except when measured near an affected
      joint (hand, hip, knee). The lower degree of bone loss with aging is explained by
      lower bone turnover as measured by bone resorption-formation parameters. OA cases
      not only have higher apparent and real bone density, but also wider geometrical
      measures of the skeleton, diameters of long bones and trabeculae, both
      contributing positively to better strength and fewer fragility fractures. Not
      only is bone quantity in OA different but also bone quality, compared with
      controls and OP cases, with increased content of growth factors such as IGF and
      TGFbeta, factors required for bone repair. Furthermore, in vitro studies of
      osteoblasts recruited from OA bone have different differentiation patterns and
      phenotypes. These general bone characteristics of OA bone may explain the inverse
      relationship OA-OP and why OA cases have fewer fragility fractures. The role of
      bone, in particular subchondral bone, in the pathophysiology, initiation and
      progression of OA is not fully elucidated and is still controversial. In 1970, it
      was hypothesized that an increased number of microfractures lead to an increase
      in subchondral bone stiffness, which impairs its ability to act as a shock
      absorber, so that cartilage suffers more. Although subchondral bone is slightly
      hypomineralized because of local increased turnover, the increase in trabecular
      number and volume compensates for this, resulting in a stiffer structure. There
      is also some experimental evidence that osteoblasts themselves release factors
      such as metalloproteinases directly or indirectly from the matrix, which
      predispose cartilage to deterioration. Instead, the osteoblast regenerative
      capacity of bone in OP is compromised compared with OA, as suggested by early
      cell adhesion differences. The proposition that drugs which suppress bone
      turnover in OP, such as bisphosphonates, may be beneficial for OA is speculative.
      Although bone turnover in the subchondral region of established OA is increased,
      the general bone turnover is reduced. Further reduction of bone turnover,
      however, may lead to overmineralized (aged) osteons and loss of bone quality,
      resulting in increased fragility.

PMID- 14703010
TI  - The tumor microenvironment: a critical determinant of neoplastic evolution.
AB  - Evolution of neoplastic cells has generally been regarded as a cumulative
      intrinsic process resulting in altered cell characteristics enabling enhanced
      growth properties, evasion of apoptotic signals, unlimited replicative potential
      and gain of properties enabling the ability to thrive in ectopic tissues and in
      some cases, ability to metastasize. Recently however, the role of the neoplastic
      microenvironment has become appreciated largely due to the realization that
      tumors are not merely masses of neoplastic cells, but instead, are complex
      tissues composed of both a non-cellular (matrix proteins) and a cellular
      'diploid' component (tumor-associated fibroblasts, capillary-associated cells and
      inflammatory cells), in addition to the ever-evolving neoplastic cells. With
      these realizations, it has become evident that early and persistent inflammatory
      responses observed in or around many solid tumors, play important roles in
      establishing an environment suitable for neoplastic progression by providing
      diverse factors that alter tissue homeostasis. Using cutaneous melanoma and
      squamous cell carcinoma as tumor models, we review the current literature
      focussing on inflammatory and tumor-associated fibroblast responses as critical
      mediators of neoplastic progression for these malignancies.

PMID- 14703011
TI  - A basement membrane-like matrix formed by cell-released proteins at the
      medium/air interface supports growth of keratinocytes.
AB  - Epithelial cells require adherence to a matrix for regular growth. During
      standard keratinocyte cell culture in serum-free medium, we observed that cell
      colonies formed not only on the bottom of the culture vessels but also at the
      medium/air interface. Coomassie blue staining detected a protein membrane that
      extended up to several centimeters between the colonies of floating cells.
      Ultrastructural investigation of this membrane revealed structures closely
      resembling those of basement membranes, and immunochemical staining confirmed the
      presence of laminins-1 and -5 as well as collagen IV, representative components
      of basement membranes. Cells attached to the floating membrane proliferated and
      could be cultivated for up to six months. When keratinocyte-conditioned medium
      was filtered and transferred to a culture vessel without cells, the protein
      membrane at the liquid/air interface formed within one week suggesting self
      assembly of cell-released proteins. Our findings provide a basis for the
      production of epidermal basement membranes for potential medical uses.

PMID- 14703012
TI  - Functional analysis of the single calmodulin gene in the nematode Caenorhabditis
      elegans by RNA interference and 4-D microscopy.
AB  - Calmodulin (CaM), a small calcium-binding protein, is the key mediator of
      numerous calcium-induced changes in cellular activity. Its ligands include
      enzymes, cytoskeletal proteins and ion channels, identified in large part by
      biochemical and cell biological approaches. Thus far it has been difficult to
      assess the function of CaM genetically, because of the maternal supply in
      Drosophila and the presence of at least three nonallelic genes in vertebrates.
      Here we use the unique possibility offered by the C. elegans model system to
      inactivate the single CaM gene (cmd-1) through RNA interference (RNAi). We show
      that the RNAi microinjection approach results in a severe embryonic lethal
      phenotype. Embryos show disturbed morphogenesis, aberrant cell migration
      patterns, a striking hyperproliferation of cells and multiple defects in
      apoptosis. Finally, we show that RNAi delivery by the feeding protocol does not
      allow the efficient silencing of the CaM gene obtained by microinjection. General
      differences between the two delivery methods are discussed.

PMID- 14703013
TI  - Platelets induce reactive oxygen species-dependent growth of human skin
      fibroblasts.
AB  - A growing amount of evidence suggests that reactive oxygen species (ROS), such as
      hydrogen peroxide and superoxide anion, regulate intracellular signalling and
      have a role in cell proliferation. In the present study, we show that platelets
      increase the mitogenic rate in human fibroblasts and that this effect was
      inhibited by the intracellular antioxidant N-acetyl-L-cysteine (NAC) and the
      NADPH-oxidase inhibitor diphenyleneiodonium chloride (DPI). The mitogenic effects
      of platelets were mimicked by the platelet factors platelet-derived growth factor
      BB-isoform (PDGF-BB), transforming growth factor beta1 (TGF-beta1) and
      sphingosine-1-phosphate (S1P). The sphingosine kinase inhibitor DL-threo
      dihydrosphingosine (DL-dihydro) abrogated the platelet-induced growth, while
      antibodies directed against PDGF or TGF-beta had modest effects. Exposure of
      fibroblasts to platelets, PDGF-BB, TGF-beta1 or S1P caused an extensive
      intracellular ROS production, measured as changes in dichlorofluorescein
      fluorescence. This ROS production was totally inhibited by NAC,
      pyrrolidinethiocarbamate (PDTC), DPI and apocynin. In conclusion, the results
      presented are indicative of a crucial role of ROS in the platelet-mediated
      regulation of fibroblast proliferation.

PMID- 14703014
TI  - Localization of an alkyl-acetyl-glycerol-CDP-choline: cholinephosphotransferase
      activity in submitochondrial fractions of Tetrahymena pyriformis.
AB  - Tetrahymena pyriformis contains platelet-activating factor (PAF) as a minor
      lipid, which is biosynthesized de novo. A dithiothreitol-insensitive CDP
      choline:cholinephosphotransferase (AAG-CPT), which utilizes alkyl-acetyl-glycerol
      as a substrate, had been detected in both the mitochondrial and microsomal
      fractions of the protozoan. In the present report, localization of this enzyme in
      submitochondrial fractions was studied. Cell fractionation was evaluated with
      enzyme and morphological markers. In this respect, succinate dehydrogenase,
      NADPH:cytochrome c reductase, glucose-6-phosphatase, alkaline phosphatase,
      monoaminoxidase, and cytochrome c oxidase activities were investigated. In the
      presence of antimycin A, mitochondrial activity of NADPH-cytochrome c reductase,
      was increased, while the microsomal one was reduced. Cardiolipin was distributed
      in the inner mitochondrial membrane. Alkaline phosphatase was found exclusively
      in the cytosol of the protozoan. The main portion of the dithiothreitol
      insensitive AAG-CPT was localized in the inner mitochondrial membrane. Our data
      indicate that mitochondria are able to produce PAF, which might be associated
      with their function.

PMID- 14703015
TI  - Regulation of corticotropin releasing hormone receptor (CRH-R) in the rat
      anterior pituitary as assessed by radioimmunoassay.
AB  - Since the cloning of corticotropin releasing hormone receptor type 1 (CRH-R1), an
      essential component of the hypothalamo-pituitary-adrenal (HPA) axis, numerous
      studies have been conducted to monitor its changes in transcription levels under
      various conditions. However, the precise dynamics at the protein levels are yet
      to be elucidated. In the present study we aimed at establishing an RIA system for
      CRH-R1 protein, with an antiserum against the C-terminal fragment of human/rat
      CRH-R1. The generated antiserum showed a moderate cross-reactivity with CRH-R2.
      We examined the in vivo effect of adrenalectomy (ADX) on immunoreactive CRH-R
      (irCRH-R) levels in the rat AP, and the in vitro profile of irCRH-R levels in
      cultured rat AP cells after administration of CRH. The irCRH-R in the AP membrane
      of intact rats was 51.8 +/- 6.8 fmol/mg protein, which is comparable to those
      reported in binding studies. ADX elicited a significant decrease of irCRH-R to
      approximately 50% of the control level one day after ADX, which returned to the
      baseline level the following day. Addition of CRH to cultured AP cells resulted
      in a significant decrease of irCRH-R in the membrane fraction to 18% of the
      control level at 4 h, and it returned rapidly to 70% at 8 h. These experiments
      together with our previous study implicate that irCRH-R makes a different
      profile, with an earlier recovery than that of mRNA. Although this system cannot
      precisely discriminate between CRH-R1 and CRH-R2, our findings may serve to
      demonstrate differing CRH receptor regulations at the synthesis level and at the
      protein level in the rat AP.

PMID- 14703016
TI  - G protein mutations in pituitary tumors: a study on Turkish patients.
AB  - Activating mutations of the G proteins, Gsalpha (gsp) and Gi2alpha (gip) have
      been reported in subsets of pituitary tumors. The objective of the study was to
      assess the frequency of gsp and gip mutations in pituitary tumors from Turkish
      patients and to investigate the possibility of mutations of protein kinase A
      catalytic subunit (PKAC) that activates the downstream effectors of adenylyl
      cyclase. PCR-amplified genomic DNA was analyzed for the presence of mutations in
      codons 201 and 227 of Gsalpha, codon 179 and 205 of Gi2alpha and codon 196 of
      PKAC, by single strand conformation polymorphism analysis, allele-specific
      oligonucleotide hybridization and DNA sequencing. Twenty-two patients from
      Turkey, 15 females and 7 males were investigated; 7 somatotroph adenomas, 7
      clinically non-functioning tumors, 7 prolactinomas and 1 corticotroph adenoma. G
      protein mutations were identified in 6 of 22 (27.3%) pituitary tumors. Four
      tumors (3/7 somatotroph adenomas, 43%, 1/7 clinically non-functioning tumor)
      demonstrated gsp mutations at codon 201 arginine to cysteine and one recurrent
      somatotroph adenoma demonstrated a mutation of the Gi2alpha gene at codon 193
      lysine to arginine. One tumor exhibited a C to T variation in the intervening
      sequence between codons 179 and 205 of the Gi2alpha gene. No mutations at codon
      227 of Gsalpha, codons 179 and 205 of Gi2alpha and codon 196 of the PKAC gene
      were identified.

PMID- 14703017
TI  - Quality of life in patients with a pituitary adenoma.
AB  - A validated quality of life (QOL) measure, the SF-36 questionnaire, was used to
      assess patients' perception of the impact of a pituitary adenoma, prior to
      treatment, on his or her physical and mental functioning. Of 270 new patients
      evaluated for pituitary disease at the University of Virginia Pituitary Clinic,
      168 met the criteria for inclusion (pituitary hormone hypersecretion and/or
      pituitary adenoma) into this prospective study. Results of the SF-26
      questionnaire in 36 patients with acromegaly, 42 patients with Cushing's disease,
      39 patients with a prolactinoma and 51 patients with a non functioning
      macroadenoma prior to treatment were compared with those of the normal
      population; a comparison of results among patients with different types of
      pituitary adenomas was also performed. Patients with a pituitary adenoma had a
      significantly decreased QOL compared with the normal population in both physical
      and mental measures (p < 0.05). There were different degrees of perceived
      impairment depending on the type of pituitary adenoma. Patients with acromegaly
      had impairment in measures of physical function while patient with Cushing's
      disease had impairment in all but one measures compared with the normal
      population and with patients with other types of pituitary adenomas. Patients
      with a prolactinoma had impairment in mental measures and patients with a non
      functioning adenoma had impairment in both physical and mental measures compared
      with the normal population. Patients with a pituitary adenoma have an impaired
      quality of life that should be routinely assessed in conjunction with endocrine
      and anatomic studies before and after treatment.

PMID- 14703018
TI  - Development of new prolactin analogs acting as pure prolactin receptor
      antagonists.
AB  - Prolactin (PRL) promotes tumor growth, as recently highlighted by the spontaneous
      appearance of prostate hyperplasia and mammary neoplasia in PRL transgenic mice.
      Increasing experimental evidence argues for the involvement of autocrine PRL in
      this process. Human (h)PRL receptor antagonists have been developed to counteract
      these undesired proliferative actions of PRL. However, all PRL receptor
      antagonists obtained to date exhibit partial agonism, limiting their therapeutic
      use as full antagonists. This is the case for the first generation antagonists
      (the prototype of which is G129R-hPRL) that we developed ten years ago, which
      display antagonistic activity in some, but not all in vitro bioassays, and fail
      to inhibit PRL activity in transgenic mice expressing this analog. We recently
      developed new human PRL antagonists devoid of agonistic properties, and therefore
      able to act as pure antagonists. This was demonstrated using several in vitro
      bioassays, including assays able to detect extremely low levels of receptor
      activation. These new compounds also act as pure antagonists in vivo, as
      demonstrated by their ability to competitively inhibit PRL-triggered signaling
      cascades in various target tissues (liver, mammary gland and prostate). Finally,
      using transgenic mice specifically expressing PRL in the prostate, which have
      constitutively activated signaling cascades and prostate hyperplasia, these new
      PRL analogs are able to completely revert PRL-activated events to basal levels.
      These second generation antagonists are good candidates to be used as inhibitors
      of the growth-promoting actions of hPRL.

PMID- 14703019
TI  - Effects of growth hormone and prolactin on adipose tissue development and
      function.
AB  - GH and PRL are both implicated in adipose tissue development. Whilst direct
      effects of GH have been clearly demonstrated, direct effects of PRL have been
      subject to considerable debate. Recent studies have however provided compelling
      evidence for PRL receptors on adipocytes and in vitro effects on leptin and
      lipoprotein lipase activity have been demonstrated. Quantitatively however these
      effects of PRL are less significant than those of GH and the most pronounced
      effects of PRL on adipose tissue are indirect, for example, during lactation,
      when prolactin drives milk synthesis which results in a homeorhetic shift towards
      lipid mobilization from adipose tissue to support milk production. GH also
      exhibits such homeorhetic effects, most notably in ruminants, but also clearly
      has direct, insulin-antagonistic, metabolic effects. The roles of GH and PRL on
      adipocyte proliferation and differentiation have also been controversial, with GH
      stimulating adipocyte differentiation in vitro in cell lines whilst stimulating
      proliferation and inhibiting differentiation of primary cell cultures.
      Examination of adipose tissue development in PRLRko and GHRko mice has revealed
      roles for both hormones. PRLRko mice show impaired development of both internal
      and subcutaneous adipose tissue due to decreased numbers of adipocytes. In
      contrast, GHRko mice exhibit major decreases in the number of internal
      (parametrial) adipocytes whereas subcutaneous adipocytes develop almost normally.
      This leads to major changes in the sites of adipose tissue accretion and bears
      interesting parallels with the adipose tissue redistribution which occurs in HIV
      induced lipodystrophy. Such individuals exhibit a central obesity which can be
      partially corrected by GH treatment. However, recent studies suggest that this
      may be a physiological response in which adipose tissue sites containing lymphoid
      tissue (such as mesenteric) show preservation of adipose tissue perhaps to
      support augmented immune responses.

PMID- 14703020
TI  - Radiotherapy for non-functioning pituitary tumors--when and under what
      circumstances?
AB  - The role of pituitary radiotherapy (RT) in the management of clinically non
      functioning pituitary tumors (NFTs) remains controversial. Observational studies
      suggest that RT is effective in preventing the regrowth of NFT remnants following
      initial surgical debulking. However, not all tumor remnants will regrow in the
      absence of pituitary RT. Furthermore there are concerns relating to potential
      complications of pituitary RT, particularly hypopituitarism and its associated
      excess mortality. In the absence of any clear consensus guidelines relating to
      the application of pituitary RT in this setting, the following text sets out to
      review the evidence base for the efficacy of RT in preventing NFT regrowth and
      attempts to balance this against the potentially deleterious consequences of
      pituitary RT. A pragmatic approach is adopted with a view to offering clinically
      relevant guidance for managing patients with postoperative NFT remnants.

PMID- 14703021
TI  - Successful management of a pregnant woman with a TSH secreting pituitary adenoma
      with surgical and medical therapy.
AB  - We described a 39-yr-old asian female who was initially diagnosed with
      prolactinoma and presented with increase nervousness and weight loss. Laboratory
      evaluation revealed an inappropriately normal TSH level with elevated free T4,
      total T3, alpha-subunit and prolactin level. The alpha-subunit/TSH molar ratio
      was 4. MRI showed a macroadenoma extending to the suprasellar cistern. Treatment
      was begun with propylthiouracil and bromocriptine. After 5 months of therapy, she
      became pregnant. At 27 weeks of gestation, she developed headache and decreased
      visual acuity in her left eye. MRI showed a slightly increase in tumor size
      compressing the optic chaiasm. Transphenoid macroadenectomy was performed with
      immediate relief of the visual field abnormality. At 39 weeks gestation a baby
      with no malformations was delivered. This is the second case report of TSH
      secreting pituitary adenoma which was exarcerbated during pregnancy. In contrast
      to the first case, our case was managed with both surgical and medical approach.
      The judicious use of both medical and surgical therapy can result in a successful
      outcome to mother and fetus in a patient with TSH secreting pituitary adenoma.

PMID- 14703022
TI  - Working with and for patients.

PMID- 14703023
TI  - Consultant appraisal.

PMID- 14703024
TI  - Medicine, the arts and humanities.

PMID- 14703025
TI  - Management of mild to moderate chronic renal failure.

PMID- 14703027
TI  - Clinical management of polycystic kidney disease.

PMID- 14703026
TI  - Clinical management of anaemia pre-endstage renal failure.

PMID- 14703028
TI  - Indications for renal biopsy in chronic kidney disease.

PMID- 14703029
TI  - Clinical use of diuretics.

PMID- 14703030
TI  - When should atheromatous renal artery stenosis be considered? A guide for the
      general physician.

PMID- 14703031
TI  - Modernising medical careers.
AB  - Modernising medical careers proposes the introduction of Basic Medical Training
      (BMT) programmes to replace senior house officer (SHO) rotations. The current pre
      registration house officer year and a broad-based first SHO year will become
      Foundation Years 1 and 2. This will be followed by a programme with eight
      options. To become a physician would entail doing the Medical Programme (as
      distinct from surgical, general practice, etc), and at the end of this a
      Certificate of Completion of Training in general internal medicine could be
      awarded. Specialty training will follow sequentially. Advantages, disadvantages
      and uncertainties of this proposal are discussed.

PMID- 14703032
TI  - Managing the difficult consultation.
AB  - Patients are more likely to develop psychological problems if their concerns are
      unresolved and their information needs unmet. However, many health professionals
      are uncertain how to elicit patients' concerns or tailor information
      appropriately. These difficulties may also lead to psychological problems for the
      health professional. Feeling inadequately trained in communication skills has
      been linked to burnout amongst senior doctors working in cancer. Clinicians find
      that some consultations are particularly hard to manage; for example, when
      patients are highly distressed, angry, withdrawn or in denial. Barriers to
      effective communication are patient-led as well as doctor- or nurse-led but
      relevant training can help overcome those barriers. The article described one
      training model that is effective in improving health professionals' skills.
      Specific strategies are suggested that can help in the more difficult
      consultations and so enable clinicians to talk to patients about their concerns
      and worries more freely.

PMID- 14703033
TI  - Between two cultures: the expert clinician and the pharmaceutical industry.
AB  - Expert clinicians, valued for their academic status and independence, are used by
      the pharmaceutical industry for advice, for contract research, and as a means of
      conveying their message to other clinicians. Both academics and industry depend
      upon this interaction, but there is a fundamental clash of cultures at the
      interface between the two. Independence cannot be marketed for a fee, opinion too
      easily shades into advocacy, and secrecy and science do not mix. Formal
      guidelines and declarations of interest are inadequate as a means of policing an
      interface where undisclosed amounts of money change hands so freely. In the
      absence of effective sanctions, each of us must seek a personal solution to the
      professional and ethical issues involved.

PMID- 14703034
TI  - An essential 'health check' for all medical devices.
AB  - In order to safeguard patient safety, all new or modified medical devices must be
      assessed for their safety and performance before they are used routinely in
      clinical practice. Most devices will carry a CE (Confirmity European) mark to
      demonstrate their safety, but many devices will require an alternative method of
      assessment. In this article, we discuss the procedures already in place, the
      significant gaps that exist in the system and the risk management issues. We
      consider the impact on research and clinical practice, and describe our
      comprehensive risk management system for objectively assessing the safety of any
      medical device.

PMID- 14703035
TI  - Physicians and foundation hospitals.
AB  - Foundation NHS Trusts will be constituted in the same way as Mutual Societies,
      and local people and patients will be invited to become subscribers. Subscribers
      will elect a board of governors who will appoint the non-executive directors of
      the Trusts. Foundation Trusts will be outside the performance management system,
      but will be subject to a regulator and to inspection. Contracts with
      commissioners will be legally enforceable. Issues discussed in the article
      include: financial borrowing; whether competition is being reintroduced; poaching
      staff; fears of a two-tier health service; fragmentation of the NHS; the impact
      on research and teaching; and the impact on the current 'target culture'. Local
      communities and patient groups may welcome involvement with their local
      hospitals, but special interest groups could be a danger. Foundation Trusts may
      bring back some of the better features of NHS Trusts as originally conceived, and
      offer better opportunities for clinicians to influence local policies and
      priorities. Fears of yet another organisational change are an important issue.
      Only time will tell whether the outcome will justify the effort the changes will
      involve.

PMID- 14703036
TI  - Involving patients and the public in the NHS.
AB  - Involving patients and the public in the NHS is a new strategic initiative by the
      Deparment of Health. Over time it will make a significant change to how services
      are designed and delivered. Doctors need to be aware of this new legislation and
      the change in the patient/clinician dynamic it embraces. In the clinical setting
      a change of culture is required so that doctors move to working in partnerships
      with their patients. Within trusts, hospital or otherwise, structures must be in
      place to ensure appropriate patient/public involvement. Health service workers
      and the public will need to understand the skills required from both sides for a
      constructive partnership to emerge. It is hoped that the prioritising of health
      service resources in the future will be the result of a more democratic process
      involving patients, public and health service workers.

PMID- 14703037
TI  - Prescribing and dispensing in Japan: conflict of interest?

PMID- 14703038
TI  - Clinical decision-making and mechanical ventilation in patients with respiratory
      failure due to an exacerbation of COPD.
AB  - This paper reports a study undertaken to determine whether differences exist in
      practice between respiratory physicians, general physicians and intensivists or
      between individual clinicians in initiating mechanical ventilation in respiratory
      failure due to chronic obstructive pulmonary disease (COPD), the factors
      influencing decision-making and their relation to the evidence base. Of 725
      questionnaires sent to clinicians, 350 (48%) were completed and analysed. Twenty
      five variables were included which clinicians scored 0-3 according to their
      perceived relevance in the decision. The sum of all the responses was calculated
      for each clinician: respiratory 15-68, general 12-65, intensivists 16-64. The
      most important variables in withholding ventilation were lung cancer inoperable
      due to COPD, and nursing home resident. The least important variables were
      treated depression and osteoporosis. No significant differences existed in
      practice between specialties but there were great differences between
      individuals' practices. Clinicians were influenced by similar factors, but these
      did not reflect documented poor outcome predictors. Guidelines are needed.

PMID- 14703039
TI  - Consultant appraisal: pitfalls and how to avoid them.
AB  - Appraisal for consultants offers a unique opportunity to discuss and record
      professional issues, identify constraints to practice and plan personal
      development. Participating in appraisal also offers a painless route to
      revalidation. Making the best use of the process requires preparation and
      planning on the part of the appraiser and the appraisee. This article discusses
      some of the potential pitfalls that might impede a successful appraisal outcome,
      and considers how they might be avoided. Both appraiser and appraisee should
      approach the meeting with a positive view of achievements in the past year, a
      clear focus on the issues that need discussion, and an open mind on potential
      solutions to any problems that have arisen. It is important that the organisation
      supports appraisal by responding to identified constraints, workload issues and
      resource limitations in a planned, constructive manner.

PMID- 14703040
TI  - Never quite there: a tale of resuscitation medicine.

PMID- 14703041
TI  - Ethnicity and renal disease: questions and challenges.
AB  - There are significant ethnic variations in the incidence of end-stage renal
      disease (ESRD). In the UK, the incidence of ESRD in South Asians and African
      Caribbeans is three times higher than in White Caucasians. This is partly
      explained by a high prevalence of diabetic nephropathy, but also by
      susceptibility to a wide range of other renal diseases. The relative
      contributions of genetic and environmental factors to this susceptibility are not
      yet well understood. The age structure of the population indicates that the
      prevalence of ESRD in ethnic minority populations will continue to increase more
      rapidly than in the White Caucasian population. Additional resources are required
      for renal replacement therapy in areas with substantial ethnic minority
      populations, taking into account the increased waiting times for cadaveric renal
      transplantation in these populations. Early intervention programmes to delay or
      prevent renal failure must be targeted to these high-risk populations.

PMID- 14703042
TI  - Treatment in art. Portrait of Dr Fritz Perls by Otto Dix.

PMID- 14703043
TI  - Community care of older people: policies, problems and practice.

PMID- 14703044
TI  - Human rights: the law must be accessible close at hand.

PMID- 14703045
TI  - Medical records and their recorders.

PMID- 14703046
TI  - Medical records and their recorders.

PMID- 14703047
TI  - Investigating older people.

PMID- 14703048
TI  - Melanie Davies' review of the prevention of diabetes.

PMID- 14703049
TI  - Is prolonged use of computer games a risk factor for deep venous thrombosis in
      children? Case study.

PMID- 14703050
TI  - Microbiological infections in HIV positive Bahraini patients with low CD4+ T
      lymphocyte count.
AB  - The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or
      opportunistic microbial infection most commonly found in HIV positive individuals
      differ from one area to the other. The present study reports such findings in 67
      HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T
      lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures
      were performed. Serological diagnosis was performed when indicated. Viral study
      was done serologically. The distribution of CD4+ T-lymphocyte count in the
      studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients
      (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16
      patients (23.9%) with count more than 500 cells/microl. Among patients with low
      CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from
      fungal infections 66%, bacterial infections 57% and viral infections 4.8%.
      Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis
      (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis
      (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%),
      Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection
      included H. simplex to (4.8%). Fungal infections were the highest common
      infection in thus study. The most common microbial infection was Candida
      albicans. P. carinii and Cryptococcus neoformans were less common than found in
      other studies world wide.

PMID- 14703051
TI  - Intestinal helminthic infestations among tribal populations of Kottoor and
      Achankovil areas in Kerala (India).
AB  - The present study was undertaken among 258 subjects belonging to 152 houses of
      two tribal communities (Kani and Malampandaram) settled in Kottoor and Achankovil
      areas, respectively of Thiruvananthapuram and Kollam districts in Kerala, South
      India. The survey covered people of all age groups and both the sexes from the
      study population. Out of the total 258 stool samples examined, 60 showed ova of
      one or more intestinal helminthes, showing the overall prevalence of 23.3% with a
      confidence interval of 18.5-28.45. Among the tribal populations of two areas
      studied, Achankovil area showed an increased overall prevalence rate (26.15%) as
      compared to Kottoor area (22.27%). The difference in prevalence rates of the two
      areas is found to be statistically significant (p-value 0.01). Hookworm
      infestation was found to be predominant (58.82%) in Achankovil and the remaining
      (41.1%) was due to only roundworm. Whereas in Kottoor area, roundworm infestation
      predominated (74.41%) followed by hookworm (18.6%) and other types (6.97%).
      Analysis of haemoglobin (Hb) level of the 190 study population showed that 66.32%
      were anaemic (<11 gm/dl) from both the areas. The proportions of subjects either
      moderately anaemic (7 gm/dl-11 gm/dl) or severely anaemic (<7 gm/dl) were almost
      same in the two study groups, showing a similar pattern in both the areas with no
      statistically significant difference. Haemoglobin level in relation to helminthic
      infestation revealed that in the worm infested group, 81.1% (43/53) was anaemic,
      as compared to only 60% (83/137) of non-worm infested group, showing significant
      difference (p value=0.01). Hb level in relation to helminthic infestation also
      seemed to differ in both the areas. Among the environmental factors studied in
      relation to helminthic infestation, the practice of hand wash alone was found out
      to be statistically significant, showing that habit of proper hand wash
      considerably reduces the risk of helminthic infestation.

PMID- 14703052
TI  - Prevalence of Helicobacter pylori infection among low socio-economic workers.
AB  - Epidemiological studies have shown that the prevalence of Helicobacter pylori
      infection in a community and occupational health are closely related to lifestyle
      and socio-economic status. There is little information on H. pylori profile in
      industrial workers in the literature. The aim of this study was to investigate
      the prevalence rate of H. pylori profiles among low socio-economic workers in the
      United Arab Emirates (UAE). This study was undertaken by determining IgG H.
      pylori antibody profiles among industrial exposed and referent workers, sera.
      Presence of anti-H. pylori antibodies in the frozen stored sera was determined by
      ELISA. Also, data on dietary and lifestyle were obtained. The result was
      considered positive if IgG anti-H. pylori antibody titers was > 300. People with
      seropositive levels of IgG antibodies to H. pylori were assumed to be infected
      with H. pylori. Most of the industrial workers lived in less modern
      accommodation, were less educated, ate their vegetable products unwashed and did
      not have drinking water facilities, when compared to referents. H. pylori
      serology by IgG was positive in 167 industrial workers (78.4%) and 137 in
      referent workers (64.3%) respectively, (p < 0.002). The sensitivity and
      specificity of the IgG serology assay were 94.5%, and 97.2% respectively. There
      was statistically significant difference between the exposed industrial and non
      exposed control groups in respect of their H. pylori profiles.

PMID- 14703053
TI  - Health care seeking pattern of tuberculosis patients attending an urban TB clinic
      in Delhi.
AB  - The study of pattern of health care seeking of tuberculosis patients is important
      for identification of factors which might influence delayed reporting of
      tuberculosis cases, especially the open pulmonary cases. Consecutive 301
      pulmonary TB patients, belonging to any of the categories under RNTCP, diagnosed
      at New Delhi Tuberculosis Centre or its sub-centres over a six-month period were
      assessed for health care seeking pattern. "Delay" was defined as the time over 3
      weeks that a case took to report to the area TB facility. 43.2% patients reported
      to the TB health facility on their own and others were referred by government
      hospitals (34.9%) and general practitioners (21.9%). Median delay over 3 weeks
      was 2.69 weeks for all three categories combined, with a significantly higher
      delay (3.41 weeks) for retreatment cases as compared to new cases (2.13 weeks).
      No significant differences were observed in health seeking delay in relation to
      sex, income, literacy status and source of referral and sputum status. Extensive
      health education activities can reduce this period of delay in health seeking and
      result in reduction of transmission of tuberculosis to healthy members of the
      family and community.

PMID- 14703054
TI  - Population dynamics of Culex quinquefasciatus filaria vector in Raipur City of
      Chhattisgarh State.
AB  - Indoor resting Culex quinquefasciatus were collected from 17 localities of Raipur
      City using aspirator tube between 06.00 and 08.00 hrs. at monthly intervals for
      over a period of 12 months. Mosquitoes were also collected using animal and human
      baits. A total of 4973 C. quinquefasciatus were collected in 176 man hours from
      different locations of Raipur City with a mean density of 28.26 pmh. The vector
      was recorded throughout the year with higher densities during the months of March
      (44.29 pmh), February (41.29 pmh), August (38.58 pmh) and April (37.17 pmh). The
      lower densities were recorded during July (17.05 pmh), September (16.82 pmh) and
      November (16.64 pmh). The Gudhyari and Amanaka localities recorded the highest
      and lowest densities of C. quinquefasciatus respectively. No significant
      relationship was observed between the density variation of the vector and
      variation in temperature and/or humidity in the study region.

PMID- 14703055
TI  - Knowledge and attitude towards tuberculosis in a slum community of Delhi.
AB  - A cross-sectional study was conducted among 208 adults (114 males and 94 females)
      aged 16-70 years, selected by systematic random sampling method in Lok Nayak
      Colony, Delhi to assess the knowledge and attitude towards tuberculosis (TB).
      Literacy rate was 28.4%. Only 174 (83.6%) heard of tuberculosis mainly from
      neighbours (64.9%) and friends (62.1%). Only 2.3% knew that TB was caused by a
      germ. Literates were more aware than illiterates regarding some signs and
      symptoms of TB i.e breathlessness (p=0.002), low grade fever (p=0.02), loss of
      appetite (p<0.001) and factors favouring TB e.g. overcrowding (56.4%) and poor
      diet (45.4%). Only 12.6% knew about the duration of treatment for 6-8 months and
      1.7% knew about preventive role of BCG. Tendency to discriminate TB patients was
      evident from the findings e.g 71% respondents agreed upon isolating TB patients
      from the family, 74.1% on avoiding the patient in food sharing, on quitting job
      by the patient (33%), prohibiting marriage of the patient (27.6%), shunning him
      from attending social functions (18%), etc. Extensive health education directing
      towards attitudinal change by community involvement is needed to create awareness
      and remove myths about TB in such colonies.

PMID- 14703056
TI  - Study of operational aspects of pulse polio booths during Intensified Pulse Polio
      Immunisation Campaign in assembly segments of East Delhi.
AB  - The study was undertaken with the objective of observing operational aspects of
      609 pulse polio booths established during Intensified Pulse Polio Campaign in
      East Delhi on National Immunisation Days (NID) during 2001-2002 through well
      designed format. The average number of persons present on duty at polio booths
      was 3.73 against a recommendation of 4 per booth. All the booths had vaccine
      carriers but some of them were not following the guidelines laid for maintaining
      the cold chain. One sixth "(15.4%)" of the booths needed fresh supplies of
      vaccine carrier. There is need for deployment of motivated trained manpower at
      polio booths to ensure the success of Pulse Polio Campaign. Maintenance of cold
      chain and quality assurance of vaccine administered to children in the field
      remain a challenge. More than half (55.7%) booths did not have any volunteer.
      Absence of volunteers from the community in more than half of the booths warrant
      for strengthening the linkages between the governmental agencies and the
      community.

PMID- 14703057
TI  - Do our medical students have enough knowledge of Hepatitis B ? A Delhi based
      study.
AB  - Hepatitis B virus is the world's most common blood borne viral infection.
      Occupational risk of Hepatitis B infection is well known in medical and dental
      workers especially during the professional training period. The present study was
      conducted among medical students of a Medical College in Delhi to assess their
      knowledge regarding Hepatitis B. A questionnaire was administered to the first,
      third and final year medical students regarding Hepatitis B vaccine, disease, and
      mode of spread, sequel and prevention. The knowledge regarding all aspects was
      maximum amongst the final year students as compared to first and third years.
      Knowledge regarding the booster dose of vaccine, transmission through formites,
      universal precautions for prevention was not good. There is need for
      strengthening in these areas and training in these should be started at the
      earliest.

PMID- 14703058
TI  - Seroprevalence of brucellosis in and around Varanasi.

PMID- 14703059
TI  - Cholera outbreak in rural areas of southern Rajasthan.

PMID- 14703060
TI  - Polio eradication in India--need for a humane approach.

PMID- 14703061
TI  - Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer.
AB  - Angiogenesis is a prognostic indicator in primary breast cancer regulated by
      specific angiogenic factors and their receptors. Vascular endothelial growth
      factor-A (VEGF-A), so far considered the most important, acts through
      dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase
      family of VEGF receptors. In order to study the interplay between VEGF-A and
      VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry
      in 102 breast cancers organized in a tumor tissue array system allowing semi
      quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF
      A165 was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared
      from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic
      staining of VEGF of varying intensity was observed in all samples and correlated
      with the ELISA results of VEGF content (p = 0.007). Interestingly, VEGFR2/KDR
      expression correlated with VEGF expression using immunohistochemistry, indicating
      that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high
      levels of VEGF-A165 in the protein extracts was associated with impaired short
      time survival but not long term survival whereas immunohistochemically assessed
      VEGF and VEGFR2/KDR were not significantly associated with survival. In summary,
      immunohistochemically based analysis of VEGF using a tumor tissue array system
      seems to be a useful method for VEGF quantification in breast cancer here
      validated using an ELISA based method. The tumor tissue array system enables
      opportunities of simultaneous analysis of markers engaged in angiogenesis
      justifying further studies using larger series of tumors.

PMID- 14703062
TI  - Regression of cutaneous tumor lesions in patients intratumorally injected with a
      recombinant single-chain antibody-toxin targeted to ErbB2/HER2.
AB  - ScFv(FRP5)-ETA is a recombinant single-chain antibody-toxin with binding
      specificity for ErbB2/HER2. Previously potent antitumoral activity of the
      molecule against ErbB2 overexpressing tumor cells was demonstrated in vitro and
      in animal models. Here we report on the first application of scFv(FRP5)-ETA in
      human cancer patients summarizing case reports collected in four different
      clinical centers. Eleven patients suffering from metastatic breast and colorectal
      cancers and from malignant melanoma were treated on a compassionate-use basis by
      intratumoral injection of scFv(FRP5)-ETA into cutaneous lesions once daily for 7
      10 days. Total daily doses ranged from 60 to 900 microg, and total doses per
      treatment cycle ranged from 0.6 to 6.0 mg. Treatment caused injected tumors to
      shrink in six of the 10 cases evaluated (60%). Complete regression of injected
      tumor nodules was accomplished in four patients (40%) and partial reduction in
      tumor size in another two patients (20%). Adverse reactions were restricted to
      local symptoms such as pain and inflammation at injection sites which were fully
      reversible. Only in one patient treated at the highest daily doses systemic liver
      toxicity of grade 2 was observed and treatment was discontinued on day 7. No
      hematologic, renal, and/or cardiovascular toxicities were noted. Our results
      demonstrate that local therapy with scFv(FRP5)-ETA can be effective against ErbB2
      expressing tumors justifying further clinical development of this reagent.

PMID- 14703063
TI  - The 870G>A polymorphism of the cyclin D1 gene is not associated with breast
      cancer.
AB  - A common 870G > A polymorphism in the gene for cyclin D1, CCND1, has been linked
      to alternative splicing and cancer susceptibility. To analyze its role for breast
      cancer, we determined the CCND1 genotype in 500 breast cancer patients and 500
      controls. CCND1 genotype frequencies were similar among patients and controls.
      The CCND1 genotype was furthermore not associated with tumor characteristics. We
      conclude that the CCND1 870G > A polymorphism is not associated with breast
      cancer.

PMID- 14703064
TI  - Venezuelan equine encephalitis replicon immunization overcomes intrinsic
      tolerance and elicits effective anti-tumor immunity to the 'self' tumor
      associated antigen, neu in a rat mammary tumor model.
AB  - Many tumor-associated antigens (TAAs) represent 'self' antigens and as such, are
      subject to the constraints of immunologic tolerance. There are significant
      barriers to eliciting anti-tumor immune responses of sufficient magnitude. We
      have taken advantage of a Venezuelan equine encephalitis-derived alphavirus
      replicon vector system with documented in vivo tropism for immune system
      dendritic cells. We have overcome the intrinsic tolerance to the 'self' TAA rat
      neu and elicited an effective anti-tumor immune response using this alphavirus
      replicon vector system and a designed target antigen in a rigorous rat mammary
      tumor model. We have demonstrated the capacity to generate 50% protection in
      tumor challenge experiments (p = 0.004) and we have confirmed the establishment
      of immunologic memory by both second tumor challenge and Winn Assay (p = 0.009).
      Minor antibody responses were identified and supported the establishment of T
      helper type 1 (Th1) anti-tumor immune responses by isotype. Animals surviving in
      excess of 300 days with established effective anti-tumor immunity showed no signs
      of autoimmune phenomena. Together these experiments support the establishment of
      T lymphocyte dependent, Th1-biased anti-tumor immune responses to a non-mutated
      'self' TAA in an aggressive tumor model. Importantly, this tumor model is subject
      to the constraints of immunologic tolerance present in animals with normal
      developmental, temporal, and anatomical expression of a non-mutated TAA. These
      data support the continued development and potential clinical application of this
      alphaviral replicon vector system and the use of appropriately designed target
      antigen sequences for anti-tumor immunotherapy.

PMID- 14703065
TI  - Dose-dense vinorelbine and paclitaxel with granulocyte colony-stimulating factor
      in metastatic breast cancer patients: anti-tumor activity and peripheral blood
      progenitor cell mobilization capability.
AB  - We studied the safety, activity and peripheral blood progenitor cell mobilizing
      capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX)
      as first-line chemotherapy for patients with metastatic breast cancer (MBC).
      Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX
      175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem
      high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5
      microg/kg was administered daily from day +5 to +10 in order to accelerate
      hematopoietic recovery, or 48h after the last VNB-PTX when a leukapheresis was
      planned (after the third or fourth cycle). A total of 172 cycles were
      administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86
      mg/m2/week, respectively (98% of the planned dose-intensity). The main per
      patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation
      (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological
      toxicity was unremarkable, except for anemia with hemoglobin (Hb) values < 10
      g/dl (28%), and lymphopenia with lymphocyte counts < 1000/mm3 (28%). Two complete
      (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients,
      for an overall response rate of 66.6% (95% CI 51.6-80.9). A median of one
      apheretic procedure (range 1-3) was required to achieve the target number of 6 x
      10(6)/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 x
      10(6)/kg (range 6.4-36.5). Four cycles of dose dense VNB and PTX showed a
      favorable toxicity profile, a relevant anti-tumor activity and a high peripheral
      blood progenitor cell mobilizing activity.

PMID- 14703066
TI  - A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human
      breast carcinogenesis.
AB  - PURPOSE: The cytochrome P450 (CYP) enzymes play a critical role in the oxidative
      metabolism of a variety of endogenous and exogenous compounds, including drugs.
      Although intermediate CYP metabolites are believed to play a role in
      carcinogenesis, little is known about tissue-specific CYP expression and the role
      of local activation in breast carcinogenesis. The goals of this study are to
      identify CYPs expressed in breast tissue by measuring mRNA levels and to
      determine whether there are differences in mRNA levels between breast tumors and
      histologically-normal adjacent breast tissue. EXPERIMENTAL DESIGN: Quantitative
      reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was used to
      quantitate mRNA expression levels of 11 CYPs in 29 human breast tumor and non
      tumor adjacent tissue pairs. The CYPs examined included: CYP1A1, CYP1A2, CYPB1,
      CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. RESULTS:
      Only four CYPs were detected in breast tumor or adjacent tissue: CYP1A1, CYPB1,
      CYP2C9, CYP3A4. Each of these CYPs was expressed in at least 75% of the samples.
      Three of these CYPs are involved in estradiol hydroxylation (CYP1A1, 2-OH;
      CYP1B1, 4-OH; CYP3A4, 2- and 16-OH). CYP2C9 is involved in the conversion of
      estrone sulfate to the 16-hydroxy sulfate metabolite. Higher levels of CYP1B1 and
      3A4 were found more often in non-tumor tissue than in tumor tissue (P < 0.04).
      CYP1A1 was elevated in non-tumor tissue only among pairs in which the tumor
      expressed the estrogen receptor (ER+, P < 0.03). All of these results were
      independent of recorded clinical-pathological covariates. CONCLUSIONS: CYPs
      involved in estrogen metabolism are expressed in both tumor and non-tumor breast
      tissue. Local activation of estrogen to potentially reactive metabolites by the
      CYPs in breast tissue may play a role in initiating and promoting the
      carcinogenic process.

PMID- 14703067
TI  - Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma
      cells or late-developing metastases.
AB  - Breast cancer is noted for long periods of tumor dormancy and metastases can
      occur many years after treatment. Adjuvant chemotherapy is used to prevent
      metastatic recurrence but is not always successful. As a model for studying
      mechanisms of dormancy, we have used two murine mammary carcinoma cell lines:
      D2.0R/R cells, which are poorly metastatic but form metastases in some mice after
      long latency times, and D2A1/R cells, which form more numerous metastases much
      earlier. Previously we identified a surprisingly large population of dormant but
      viable solitary cells, which persisted in an undivided state for up to 11 weeks
      after injection of D2.0R/R cells. Dormant cells were also detected for D2A1/R
      cells, in a background of growing metastases. Here we used this model to test the
      hypothesis that dormant tumor cells would not be killed by cytotoxic chemotherapy
      that targets actively dividing cells, and that the late development of metastases
      from D2.0R/R cells would not be inhibited by chemotherapy that effectively
      inhibited D2A1/R metastases. We injected mice with D2A1/R or D2.0R/R cells via a
      mesenteric vein to target liver. We developed a doxorubicin (DXR) treatment
      protocol that effectively reduced the metastatic tumor burden from D2A1/R cells
      at 3 weeks. However, this treatment did not reduce the numbers of solitary
      dormant cells in mice injected with either D2A1/R or D2.0R/R cells. Furthermore,
      DXR did not reduce the metastatic tumor burden after an 11-week latency period in
      mice injected with D2.0R/R cells. Thus, apparently effective chemotherapy may
      spare non-dividing cancer cells, and these cells may give rise to metastases at a
      later date. This study has important clinical implications for patients being
      treated with cytotoxic chemotherapy.

PMID- 14703068
TI  - Influence of neoadjuvant therapy with epirubicin and docetaxel on the expression
      of HER2/neu in patients with breast cancer.
AB  - BACKGROUND: In primary breast cancer, the expression levels of biological markers
      relevant to the progression of the disease may be altered by administration of
      anticancer drugs. Since neoadjuvant chemotherapy with epirubicin and docetaxel is
      increasingly used in advanced breast cancer, our purpose was to assess the
      influence of this neoadjuvant chemotherapy on the expression of the growth factor
      receptor HER2/neu. PATIENTS AND METHODS: We investigated changes of HER2/neu
      status by immunohistochemistry (IHC) and applied additional fluorescence in situ
      hybridization (FISH) in patients with potential modulation of HER2/neu status
      after administration of neoadjuvant chemotherapy with docetaxel and epirubicin in
      97 breast cancer patients. The influence of neoadjuvant chemotherapy on HER2/neu
      expression was calculated by correlation of HER2/neu status before and after
      chemotherapy. RESULTS: The accuracy of HER2/neu assessment before and after
      neoadjuvant chemotherapy by IHC combined with FISH analysis in selected cases was
      100%. The evaluation of HER2/neu status in these patients by IHC alone yielded
      accuracy of 93%. Neoadjuvant chemotherapy with epirubicin and docetaxel caused no
      significant modulation of HER2/neu status (p = 0.66). DISCUSSION: The
      administration of epirubicin and docetaxel in the neoadjuvant setting is not
      associated with significant changes of HER2/neu status in primary breast cancer.
      As a consequence, drug resistance or sensitivity is not induced by modulation of
      HER2/neu expression. Moreover, the time of assessment of the HER2/neu status is
      not a critical factor under neoadjuvant therapy with epirubicin and docetaxel.

PMID- 14703069
TI  - A review of the efficacy of anastrozole in postmenopausal women with advanced
      breast cancer with visceral metastases.
AB  - Tumors that have spread to the liver or lungs (visceral metastases) are
      associated with a worse prognosis than tumors in soft tissue and bone only. Here
      we review available efficacy data to address whether or not anastrozole, a non
      steroidal aromatase inhibitor (AI), is effective in postmenopausal patients with
      advanced breast cancer (ABC) and visceral metastases. We include data from Phase
      III clinical trials, comparing clinical benefit (CB) with anastrozole versus
      tamoxifen as a first-line treatment, and versus megestrol acetate (MA) or
      fulvestrant as a second-line therapy. Patients in these trials had adequate organ
      function and the volume of disease had to be minimal or moderate for them to be
      eligible for inclusion. First-line treatment of patients with or without visceral
      metastases in the overall population resulted in CB rates of 49.5 and 62.3%,
      respectively, for anastrozole and 46.9 and 55.9%, respectively, for tamoxifen. In
      patients with confirmed hormone receptor (HR)-positive tumors, the CB rate was
      51.9 and 65.7%, respectively, for anastrozole and 41.6 and 58.7%, respectively,
      for tamoxifen. In patients with or without visceral metastases, second-line
      treatment with anastrozole resulted in a CB rate of 31.4 and 51.8%, respectively,
      compared with 31.9 and 47.1%, respectively, for those treated with MA. Patients
      in the overall population with and without visceral metastases treated with
      anastrozole obtained a CB rate of 37.4 and 43.8%, respectively, while those
      treated with fulvestrant obtained a CB rate of 38.2 and 47.6%, respectively. In
      patients with confirmed HR-positive tumors, CB was seen in 37.6 and 41.5%,
      respectively, of patients treated with anastrozole and in 37.3 and 47.0%,
      respectively, of patients treated with fulvestrant. The results reveal
      anastrozole to be an effective and valuable first- and second-line therapy in
      postmenopausal women with ABC and visceral metastases, showing similar CB to
      other endocrine therapies.

PMID- 14703070
TI  - Harvesting the genomic promise: recombineering sequences for phenotypes.
AB  - The past decade has witnessed the construction of linkage and physical maps
      defining quantitative trait loci (QTL) in various domesticated species. Targeted
      chromosomal regions are being further characterized through the construction of
      bacterial artificial chromosome (BAC) contigs in order to isolate and
      characterize genes contributing towards phenotypic variation. Whole-genome BAC
      contigs are also being constructed that will serve as the tiling path for genomic
      sequencing. Harvesting this genetic information for biological gain requires
      either genetic selection or the production of genetically modified animals. This
      later approach when coupled with nuclear transfer technology (NT) provides
      "clones" of genetically modified animals. However, to date, the production of
      genetically modified animals has been limited to either microinjection of small
      gene constructs into embryos with random insertion or complex gene constructs
      designed to knock-out targeted gene expression. Neither of these approaches
      provides for introducing directed genetic manipulation allowing for allelic
      substitution [knock-in], subsequent analyses of gene expression, and cloning. An
      alternative approach utilizing genomic sequence information and recombineering to
      direct gene targeting of specific porcine BACs is presented here.

PMID- 14703071
TI  - Microsatellite loci for genetic mapping in the turkey (Meleagris gallopavo).
AB  - New microsatellite loci for the turkey (Meleagris gallopavo) were developed from
      two small insert DNA libraries. Polymorphism at these new loci was examined in
      domestic birds and two resource populations designed for genetic linkage mapping.
      The majority of loci (152 of 168) was polymorphic in domestic turkeys and
      informative in two mapping resource populations and thus will be useful for
      genetic linkage mapping.

PMID- 14703072
TI  - Generation of EST and microarray resources for functional genomic studies on
      chicken intestinal health.
AB  - Expressed sequenced tags (ESTs) and microarray resources have a great impact on
      the ability to study host response in mice and humans. Unfortunately, these
      resources are not yet available for domestic farm animals. The aim of this study
      was to provide genomic resources to study chicken intestinal health, in
      particular malabsorption syndrome (MAS), which affects mainly the intestine.
      Therefore a normalized and subtracted cDNA library containing more than 7000
      clones was prepared. Randomly chosen clones were sequenced for control purposes.
      New ESTs were found and multiple ESTs not identified in the chicken intestine
      before were observed. The number of non-specific ESTs in this cDNA library was
      low. Based on this normalized and subtracted library a cDNA microarray was made.
      In a preliminary hybridization experiment with the microarray, genes were
      identified to be up- or downregulated in MAS infected chickens. This indicates
      that the generated resources are valuable tools to investigate chicken intestinal
      health by whole genome expression analysis approaches.

PMID- 14703073
TI  - Construction and characterization of a novel 13.34-fold chicken bacterial
      artificial chromosome library.
AB  - A chicken bacterial artificial chromosome (BAC) library consisting of 138,240
      clones was constructed in vector pBeloBAC11 with genomic DNA isolated from female
      white-silk chicken. An average insert size of 118 kb was estimated from 452
      randomly isolated clones, which indicate the library to be approximate 13.34-fold
      genome coverage. For the demonstration of the probability to pick out any unique
      genes or DNA markers from the library, 8 single-copy genes were screened out and
      the positive clones were yielded between 2 and 15 with an average of 11.125, in
      agreement with the estimated high genomic coverage of this library. Positive
      superpools were obtained for 40 microsatellite markers selected from different
      regions of chicken genome. The number of positive superpools for each marker
      varies from 1 to 15 with an average of 9.475.

PMID- 14703074
TI  - Association of rabbit sperm cells with exogenous DNA.
AB  - The ability of rabbit spermatozoa to bind exogenous DNA during sperm-mediated
      gene transfer (SMGT) was tested in our study. Fresh collected semen, or fully
      capacitated sperm cells, was co-cultured with plasmid DNA labeled with
      tetramethyrodamine-6-dUTP. Fluorescent spermatozoa were counted before and after
      DNaseI treatment. Results showed that fluorescent-labeled plasmid DNA could be
      taken up by capacitated rabbit sperm cells. 66% spermatozoa carried exogenous DNA
      in the presence of lipofectin. Bovine serum albumin could block this process
      effectively. Associated DNA was mainly located in the posterior area of the sperm
      head. In order to verify whether exogenous DNA was carried into the embryo and
      expressed in the offspring, further SMGT experiments were carried out using the
      pHM-CR plasmid which contains LacZ and Neomycin genes. beta-galactosidase was
      expressed in different stages of embryo development and in the tissues of young
      rabbit as detected by using X-gal staining. Large portion of embryos survived
      under the selection pressure in G418 containing medium, after SMGT. Transgene
      integration was further verified by PCR analysis. These results confirmed the
      ability of rabbit sperm cells to carry transgene into the embryo during in vitro
      fertilization.

PMID- 14703075
TI  - Analysis of 22 heterologous microsatellite markers for genetic variability in
      Indian goats.
AB  - The genetic variability of 22 heterologous microsatellite markers was analyzed in
      two Indian goat breeds, namely Bengal and Chegu. The heterozygosity, polymorphism
      information content (PIC), and probability of identity of two individuals were
      calculated for all microsatellite loci in both the breeds. The observed number of
      alleles varied between 4 and 13 at the studied microsatellite loci. The evaluated
      microsatellite loci exhibited high mean heterozygosity of 0.69 +/- 0.11 and 0.66
      +/- 0.07 in Bengal and Chegu goats, respectively. The mean PIC values of the
      studied loci in these breeds were 0.79 +/- 0.08 and 0.78 +/- 0.05, respectively.
      The probability of identity of two random individuals from different breeds,
      taking into account, all the 22 microsatellite loci was as low as 5.523 x 10(
      40). On the basis of these results, we propose that these microsatellite markers
      may be used with reliability for studying genetic diversity and for
      identification of individuals in Indian goat breeds.

PMID- 14703076
TI  - Organization of porcine platelet-activating factor receptor gene.
AB  - Four exons of porcine platelet-activating factor receptor (PAFr) gene expressing
      transcript 1 and transcript 2 were determined previously. In this study, we
      cloned and sequenced a new exon, which also initiates transcript 2, and
      determined the order of 5 exons in the PAFr gene. In addition, two other variants
      of transcript 2 were found, but no additional variants of transcript 1 were
      found. Transcript 2 has three variants that were detected in porcine tissues
      other than in white blood cells.

PMID- 14703077
TI  - Time to think outside the box.

PMID- 14703078
TI  - Relating to your clients on their turf.

PMID- 14703079
TI  - Ontario Equine Infectious Disease Report now available to equine practitioners
      throughout Canada.

PMID- 14703080
TI  - Fact over opinion.

PMID- 14703081
TI  - An ethicist's commentary on whether veterinarians should support activist groups.

PMID- 14703082
TI  - Feline urethral plugs and bladder uroliths: a review of 5484 submissions 1998
      2003.
AB  - The results of 5484 submissions from cats to the Canadian Veterinary Urolith
      Centre between February 1998 and February 2003 are presented. Of the submissions,
      618 were urethral plugs and 4866 were bladder uroliths. The majority of the
      urethral plugs were from male domestic shorthair and longhair cats. Approximately
      50% of the urolith submissions were oxalate, 44% were struvite. Oxalate uroliths
      were the most common mineral type in males and in Himalayan, Persian, and Siamese
      cats. Struvite uroliths were the most common mineral type in domestic shorthair
      and longhair cats. Females outnumbered males by 1.4:1 in struvite urolith
      submissions. A review of risk factors for urethral plugs and bladder uroliths is
      presented.

PMID- 14703083
TI  - [Evolution of bacterial resistance to certain antibacterial agents in horses in a
      veterinary hospital].
AB  - Evolution of bacterial resistance to certain antibacterial agents in horses in a
      veterinary hospital. A total of 255 antibiograms, conducted according to the
      Kirby-Bauer method from bacterial isolates collected from horses at the Hopital
      Veterinaire d'Enseignement at the Universite de Montreal between 1996 and 1998
      were compared with the results obtained about 10 years ago with corresponding
      bacterial species. A significant increase in the percentage of strains resistant
      to trimethoprim-sulfamethoxazole (TMP-SXT), penicilline, tetracycline, and to
      gentamicin was observed. The percentages of isolates of Actinobacillus spp. and
      coagulase-positive staphylococci resistant to TMP-SXT increased from 0% to 17%
      and from 0% to 33%, respectively, (P < 0.05). The percentage of isolates of
      Actinobacillus spp resistant to penicilline also increased from 33% to 73% (P <
      0.05). Regular monitoring of the evolution of bacterial resistance to
      antibacterial agents is indispensable in a hospital structure. The adoption of
      "good antibiotherapy practices" is essential to guarantee a decrease in the risks
      of selection and dissemination of a resistant bacterial strain.

PMID- 14703084
TI  - Evaluation of deficiencies in labeling of commercial probiotics.
AB  - Labels of 44 human or veterinary probiotics were scrutinized. Organisms were
      improperly identified in 9/21 (43%) human and 8/23 (35%) veterinary products.
      Contents of 5/20 (25%) human and 3/17 (18%) veterinary products were misspelled.
      In only 9 human and 2 veterinary products were the contents adequately
      identified.

PMID- 14703085
TI  - Osteochondrosis of the occipital condyles and atlanto-occipital dysplasia in a
      Belgian horse.
AB  - A lesion in the cervical region of a 14-month-old Belgian gelding with severe
      ataxia was suspected. Necropsy revealed symmetric focal cartilage defects
      compatible with osteochondrosis of the occipital condyles and atlanto-occipital
      dysplasia. To our knowledge this is the first equine report of symmetrical
      osteochondrosis of the occipital condyles causing neurologic signs.

PMID- 14703086
TI  - T-cell lymphoma of the tympanic bulla in a feline leukemia virus-negative cat.
AB  - This report constitutes the first description of a T-cell lymphoma of the
      tympanic bulla in a cat. This feline leukemia virus (FeLV)-negative cat
      originally presented with signs referable to middle ear disease; it deteriorated
      rapidly after definitive diagnosis. Lymphoma of the middle ear is extremely rare
      in all species.

PMID- 14703087
TI  - Temporohyoid osteoarthropathy and unilateral facial nerve paralysis in a horse.
AB  - A 13-year-old broodmare was referred for weight loss and left facial nerve
      paralysis. Bilateral temporohyoid osteoarthropathy was diagnosed based on
      proliferation of the temporohyoid joints and stylohyoid bones on radiographs and
      guttural pouch endoscopy. The left side was more severely affected. Treatment
      resulted in little or no improvement.

PMID- 14703088
TI  - Cricopharyngeal achalasia in a dog.
AB  - A 4-month-old, female terrier-poodle cross was presented with a chronic history
      of dysphagia. Fluoroscopic swallowing studies localized the problem to the upper
      esophageal sphincter. A diagnosis of cricopharyngeal achalasia was made. After
      cricopharyngeal and thyropharyngeal myectomy, the dog was able to eat soft food
      without difficulty.

PMID- 14703089
TI  - Practical bond considerations: acknowledging clients' financial limits.

PMID- 14703090
TI  - How might veterinarians do more for animal welfare?

PMID- 14703091
TI  - Strangulation of the small intestines by a mesodiverticular band in 3 adult
      horses.

PMID- 14703092
TI  - Collegeality.

PMID- 14703093
TI  - External coaptation of distal radius and ulna fractures.

PMID- 14703094
TI  - Effects of FK506 on acute allograft rejection in transplanted rat heart: the role
      of mitogen-activated protein kinases, AP-1 and NF-kappaB.
AB  - To scrutinize the effect of the immunosuppressant on acute allograft rejection as
      related to the intracellular signal transduction, heterotopic cardiac
      transplantation was performed from DA rat to Lewis rat with/without FK506. In the
      experimental group, recipients were given FK506 intramuscularly for 5 days. The
      control group received placebo. Allograft survivals were compared between two
      groups. For the assay of mitogen-activated protein kinase (MAPKs) families,
      activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in the left
      ventricular free wall (LV) and septum (SEP) of the grafts, rats were sacrificed
      on POD 5 (n=5 in each group). Extracellular signal-regulated kinase (ERK) and
      p38MAPK were measured using Western blot analysis. AP-1 and NF-kappaB DNA binding
      activities were measured by electrophoretic mobility shift assay. FK506 prolonged
      allograft survival (6.5 vs 31 days), and suppressed activation of myocardial
      MAPKs (ERK: 66% in LV and 67% in SEP, p38MAPK: 62% in LV and 72% in SEP), AP-1
      (24% in LV and 18% in SEP), and NF-kappaB (41% in LV and 20% in SEP) (the mean
      value of activities in the control group was represented as 100%). These results
      suggest that the signal transduction pathways may play important roles in acute
      allograft rejection in rat cardiac transplantation.

PMID- 14703095
TI  - Effects of prostaglandin E1 infused via the superior mesenteric artery on
      partially resected, dearterialized canine liver.
AB  - This study was performed to determine whether the infusion of prostaglandin E1
      (PGE1) via the superior mesenteric artery (SMA) lessens hypoxic hepatic injury in
      beagle dogs subjected to major hepatectomy and dearterialization. Changes in
      systemic and hepatic hemodynamics by infusion of PGE1 were measured in intact and
      dearterialized dogs. The effects of infusion at 0.02 microg/kg/min were also
      studied in dogs that underwent resection of 55% of the liver and complete
      dearterialization. PGE1 infusion significantly increased portal vein flow and
      hepatic oxygen delivery. Hepatic dearterialization remarkably decreased delivery,
      but infusion at 0.02 microg/kg/min significantly restored it to 88% of the pre
      dearterialized value. In hepatectomized animals, complete dearterialization
      provoked fatal hepatic damage, but infusion remarkably improved hepatic
      parenchymal and non-parenchymal injury. PGE1 through SMA might be useful for
      patients who have undergone major hepatectomy and combined arterial resection
      without reconstruction.

PMID- 14703096
TI  - Post-initiation inhibition of MeIQx hepatocarcinogenesis in rats by cysteine.
AB  - Rats were administered cysteine at a dose of 100 mg/kg b.w. 5 times per week
      after 2-amino-3, 8-dimethylimidazo [4,5-f] quinoxaline (MeIQx) treatment.
      Significant decrease in numbers and areas of glutathione S-transferase placental
      form (GST-P)-positive foci, putative preneoplastic lesions, and silver-stained
      nucleolar organizer regions were evident in the livers of rats treated with
      cysteine after MeIQx treatment. Morever, post-initiation stage cysteine treatment
      resulted in decreased hepatic insulin-like growth factor (IGF)-I mRNA expression.
      Thus post-initiation cysteine treatment may exert chemopreventive effect on MeIQx
      hepatocarcinogenesis.

PMID- 14703097
TI  - Possible use of nasal septum and frontal sinus patterns to radiographic
      identification of unknown human remains.
AB  - The aim of the present study was to examine the combined use of the nasal septum
      and frontal sinus pattern for systemic radiographic identification of unknown
      human remains and the limitations. Postmortem skull radiographs were collected in
      209 forensic autopsy and 163 clinical cases. In total cases, a combined use of
      the nasal septum deviation patterns (straight, left, right, sigmoid, reverse
      sigmoid and rare types) and the frontal sinus patterns (aplasia, symmetry, left
      or right dominant asymmetry in combination with the number of lobulations)
      achieved a classification of at least 204 different types (incidence up to 5%).
      Comparison of the ante- and postmortem films (n=24) gave an identical result in
      about 75%. The cases of inconsistency suggested the influences of the positioning
      in radiographic examination, the quality of radiographs and the complicated
      structures of the nasal septum and frontal sinus as possible causes of missing
      identity.

PMID- 14703098
TI  - Expression and distribution of cyclooxygenase-2 in human ovary during follicular
      development.
AB  - Prostaglandins play important roles for oocyte maturation and follicular rupture.
      Cyclooxygenase-2 (COX-2), an inducible isoform of a prostaglandin metabolic
      enzyme, is essential for the timed production of prostaglandins in the ovary. The
      aim of the present study is to examine expression and distribution of COX-2 in
      human ovarian follicles at each of the maturation stages. Immunohistochemical
      staining shows that COX-2 is expressed in the granulosa cell layer of secondary
      and developing follicles, but is not detected in primary and Graafian follicles.
      Western blotting analysis revealed the existence of COX-2 in periovulatory
      follicular fluid at a mean concentration of 5.6 +/- 0.6 ng/ml. COX-2 might begin
      to be produced at the secondary follicle stage, and once a follicle reaches the
      Graafian follicle stage, the production of this enzyme is stopped. After exposure
      to luteinizing hormone (LH) surge, follicles might resume production of COX-2,
      and this is secreted into the follicular fluid.

PMID- 14703099
TI  - Regulation of CYP2D expression in rat brain by toluene.
AB  - We investigated the expressional regulation of cytochrome P450 (CYP) 2D isoforms
      in rat brain by toluene. Toluene (10 mmol/kg) was injected intraperitoneally into
      male rats daily for 3 days. CYP2D4 level in the brain was determined by Western
      blotting. The level of CYP2D4 in the brain and the catalytic activity specific
      for this isoform were significantly increased by toluene administration. The
      expressions of CYP2D mRNAs in the brain were quantified by real time PCR. The
      mRNA level of CYP2D4 increased similar to the expression of the protein and
      enzymatic activity. These results showed that CYP2D4 was transcriptionally
      induced by toluene administration for 3 days. This is the first report that
      subacute exposure to toluene activated the expression of CYP2D4 mRNA in the
      brain. The response of CYP2D4 expression to toluene is thought to relates to the
      regulation of the physiological and pharmacological functions of CYP2D isoforms
      in the brain.

PMID- 14703100
TI  - How to smother an idea. 1964 [classical article].

PMID- 14703101
TI  - Postlaryngectomy voice restoration using a voice prosthesis: a single
      institution's ten-year experience.
AB  - We describe the speech rehabilitation outcome of patients treated with total
      laryngectomy or total laryngopharyngectomy and insertion of Provox voice
      prostheses (Atos Medical AB, Horby, Sweden) at the Helsinki University Central
      Hospital. We performed a retrospective chart review of 95 patients (88 men and 7
      women; mean age, 63.5 years) who underwent insertion of a voice prosthesis in the
      period 1992 to 2002. Eighty-one percent (77/95) of the patients underwent a
      primary prosthesis insertion at the time of laryngectomy. A head and neck
      surgeon, a laryngologist, and a speech therapist rated the long-term
      tracheoesophageal speech of 78% (74/95) of the patients as good or average. The
      main causes for replacement of the device were obstruction, leakage or inadequate
      size of the prosthesis, and granulation or leakage around the fistula. According
      to our 10-year experience, use of the Provox prosthesis is an effective method of
      postlaryngectomy voice rehabilitation, and it continues to be our preferred
      method of voice restoration in the majority of cases.

PMID- 14703102
TI  - Development of a canine model for recurrent respiratory papillomatosis.
AB  - A canine model for recurrent respiratory papillomatosis (RRP) was developed with
      canine oral papillomavirus (COPV) inoculated into the buccal mucosa and
      supraglottic larynx of 5 beagles. The animals received systemic immunosuppression
      with daily oral prednisone at doses of 0, 1, 2, 3, and 4 mg/kg. Buccal
      papillomata developed at 6 weeks in all animals and regressed by 10 weeks in the
      animals that received 0 and 1 mg/kg. The other animals had continuous growth of
      their buccal papillomata for 26 weeks. The animal that received 2 mg/kg developed
      papillomata on the lingual surface of the epiglottis that continued to grow
      through 26 weeks. Systemic oral prednisone successfully maintained COPV-induced
      oral and laryngeal papillomata in beagles. Thus, COPV-induced oral and laryngeal
      papillomata that are prednisone-maintained may have utility as a model for RRP.

PMID- 14703103
TI  - Spirometric and plethysmographic assessment of upper airway obstruction in
      laryngeal hemiplegia.
AB  - Laryngeal hemiplegia (LH) is the most common disorder of laryngeal motility. It
      is deemed not to cause obstruction of the upper airway; in fact, the main
      symptoms are dysphonia and breathiness, and respiratory impairment is not
      commonly reported. The aim of this study was to objectively assess upper airway
      patency in 41 patients affected by LH (mean age, 54.4 +/- 15.2 years; 27 female)
      and 30 controls (mean age, 50.0 +/- 16.1 years; 19 female) by means of flow
      volume loop spirometry and body plethysmography to measure specific airway
      resistance (sRaw) at increasing respiratory frequencies. The causes of LH were
      cervical surgery (28), tumor infiltration (5), and unexplained (8). None of the
      patients or controls was affected by lower airway disease. Spirometry showed that
      the patients had inspiratory flows (PIF, FIF50) significantly lower than those of
      the controls (p < .0001), whereas the expiratory flows (FEV1, FEF50) were normal,
      with the exception of peak expiratory flow (PEF), which was reduced, especially
      in female patients. The mean FEF50/FIF50 ratio (about unity in the normal
      subjects) was >1, as is typical of variable extrathoracic obstruction.
      Plethysmography showed that the values of sRaw of the LH group were not
      statistically different from those of the controls at 30 +/- 5 breaths per
      minute, but they progressively and significantly increased at 60 +/- 5 (p < .01)
      and 90 +/- 5 breaths per minute (p < .002), whereas no significant sRaw change
      was observed in the controls. These results show that LH causes obstruction of
      the upper airway that can be assessed and quantified by means of spirometry and
      body plethysmography. A dynamic narrowing due to inspiratory medialization of the
      paralytic vocal fold and flow turbulence during hyperventilation seem to be the
      causes of patency impairment. The flow-volume loop is an excellent, inexpensive,
      and easily available means of functionally evaluating upper airway obstruction,
      but some patients have difficulty in performing an inspiratory test that requires
      maximal effort, and the flow reduction during forced ventilation may be partially
      due to the effort dependency of the tests themselves. Plethysmographic assessment
      of airway resistance may be a valid alternative or complement, as it reveals an
      increase in sRaw at increasing respiratory frequencies.

PMID- 14703104
TI  - Shifts in biochemical markers associated with wound healing in laryngeal
      secretions following phonotrauma: a preliminary study.
AB  - The current study sought to determine whether shifts in key components of the
      inflammatory process could be detected from laryngeal secretions sampled before
      and after vocal loading. A healthy 44-year-old woman served as the subject. The
      vocal folds were swabbed to collect baseline secretions. Ten and 20 minutes after
      nearly constant loud phonation for 1 hour, the vocal folds were swabbed again.
      The findings indicated strong shifts in several key inflammatory mediators:
      interleukin-1beta, tumor necrosis factor alpha, and matrix metalloproteinase 8.
      The concentrations of those mediators continued to increase from the 10- to 20
      minute postloading time-points. Transforming growth factor beta and prostaglandin
      E2 did not demonstrate clear shifts. In summary, mediators reflecting the acute
      inflammatory process could be detected from laryngeal secretions in an awake
      human. The upward slope of the curves at the 20-minute time interval indicates
      the need for longer follow-up sampling to determine the full biological response
      of the vocal folds to acute phonotrauma.

PMID- 14703105
TI  - Morphological and functional changes of human vocal fold fibroblasts with
      hepatocyte growth factor.
AB  - Fibroblasts produce extracellular matrix and play an important role in wound
      healing and scarring. Hepatocyte growth factor (HGF) has strong antifibrotic
      activity, and has been suggested to have therapeutic potential for treatment of
      fibrotic diseases. In the present in vitro study, morphological and functional
      changes of human vocal fold fibroblasts with HGF were examined by transmission
      electron microscopy and enzyme-linked immunosorbent assay to help clarify the
      potential use of HGF in the prevention or treatment of vocal fold scarring. The
      HGF stimulated the production of hyaluronic acid (HA) and decreased the
      production of collagen type I from the fibroblasts in Reinke's space (FbRS),
      whereas fibronectin production was not affected. The HGF also changed the shape
      of the FbRS from an oval shape toward a spindle and stellate shape, and developed
      Golgi apparatus (GA) and rough endoplasmic reticulum (rER) in the FbRS. The
      fibroblasts in the macula flava (FbMF) presented with much more production of HA
      and collagen type I than did FbRS, and were more frequently formed in a stellate
      shape with well-developed GA and rER. The HGF decreased the production of
      collagen type I from the FbMF, but barely affected the FbMF in terms of the shape
      of the cells, the development of GA and rER, or the production of HA. These
      results were interpreted to suggest that the FbMF are not as susceptible to HGF
      as are FbRS. On the contrary, HGF appeared to activate the FbRS and modify the
      function. The increased HA and decreased collagen type I production from the FbRS
      suggest that HGF may be useful in the prevention or treatment of fibrotic vocal
      fold scarring.

PMID- 14703106
TI  - Ameloblastoma revisited.
AB  - Ameloblastoma is a benign but locally aggressive neoplasm of the odontogenic
      epithelium, the treatment of which is controversial. A review was made of 22
      patients treated for histologically diagnosed ameloblastoma between January 1975
      and January 2000. We recorded data relating to patient sex, age, site of
      involvement, histologic type, surgical treatment, and number of recurrences. All
      ameloblastomas were located in the mandible. The most common histologic patterns
      were follicular and plexiform lesions. A total of 22.7% of the tumors were
      unicystic ameloblastomas. Unicystic lesions were seen to affect younger patients
      than the rest of the histologic types. Eighteen patients were initially treated
      in our center, and 4 cases were referred to our center for secondary treatment.
      The number of recurrences was significantly lower in patients initially treated
      in our center. Primary treatment comprised enucleation and bone curettage in 10
      cases and radical surgery in 7. Forty percent of the unicystic lesions and 53.3%
      of the non-unicystic ameloblastomas of our study presented at least 1 recurrence.
      Ameloblastoma is a polymorphic neoplasm for which the treatment is conditioned by
      a number of clinical and histologic factors. An individualized preoperative study
      is essential for treatment.

PMID- 14703107
TI  - Involuntary expiratory phonation as a dose-related consequence of L-dopa therapy
      in a patient with Parkinson's disease.
AB  - We report a case of involuntary phonation caused by abnormal vocal cord movements
      during expiration in a patient with Parkinson's disease. A 60-year-old woman had
      been treated for parkinsonism at the outpatient clinic of the Department of
      Neurology since August 1999. She began to groan involuntarily in the daytime in
      September 2001. She could not eat well while groaning. Stridor was not noted
      during sleep at night. Endoscopic examination of the larynx revealed insufficient
      abduction of the bilateral vocal cords, although the glottis was not so small as
      to cause stridor during inspiration. During expiration, however, the vocal cords
      adducted, resulting in the involuntary production of voice. Electromyography
      showed an increase in the activity of the thyroarytenoid and lateral
      cricoarytenoid muscles. This muscle activity was further enhanced during
      inspiration. The involuntary phonation disappeared when the patient's dose of L
      dopa was decreased, although she had a decrease in her systemic mobility as well.
      When the dose of L-dopa was increased to the therapeutic level, involuntary
      phonation recurred, and her voluntary systemic activity improved. In the present
      case, it was considered that excessive dopaminergic denervation occurred in the
      nerve innervating the laryngeal adductors. Involuntary voice appeared to be
      produced by hypertonus of the laryngeal adductors because of a lowering in the
      threshold level for L-dopa, even though the drug was administered at the usual
      dose.

PMID- 14703108
TI  - Carbon dioxide laser vaporization of the inferior turbinate for allergic
      rhinitis: short-term results.
AB  - Carbon dioxide laser vaporization of the turbinate has recently become accepted
      as a common treatment for allergic rhinitis. Usually, only a single procedure is
      applied to minimize trauma. However, repeated procedures on separate days are
      often required to achieve an adequate effect. Therefore, we attempted a new
      method of vaporization and evaluated the outcome, and also tried to determine
      which patients have good indications for laser treatment. To widely and deeply
      vaporize the inferior turbinate, we repeated the procedure 3 times in 1 session
      after removing the carbon coating from the previous vaporization under nasal
      endoscopic observation. After the procedure, most patients experienced complete
      nasal obstruction for 2 or 3 days, but there was no intraoperative or
      postoperative bleeding or severe pain. All patients obtained improvement of their
      chief complaints and were satisfied 2 months after the operation. In particular,
      60% of the patients were completely relieved of refractory nasal obstruction.
      Most patients were more satisfied with the effects than are those treated by the
      usual methods. Completely successful cases (improvement in all symptoms and
      complete satisfaction obtained) were selected and were compared with other cases.
      Favorable prognostic factors are more severe complaints, longer symptomatic
      periods, stronger allergic reactions, and worse nasal resistance and its greater
      improvement with administration of decongestant nasal drops. This method may be
      especially accepted by patients with severe complaints, in particular nasal
      obstruction, who do not experience enough relief with conservative therapies or
      have enough time to make frequent visits to an outpatient clinic over a period of
      several weeks.

PMID- 14703109
TI  - Intraoperative electrically elicited stapedius reflex threshold is related to the
      dosage of hypnotic drugs in general anesthesia.
AB  - Today cochlear implantation is a widely used means of treatment in deafness and
      severe hearing disorders in adults, children, and infants. Postoperative fitting
      of the externally worn speech processor is very important for successful use of
      the cochlear implant. However, especially in infants and young children, this
      fitting process can be difficult because of limited communication capabilities.
      The use of intraoperatively obtained stapedius reflex thresholds has been
      proposed for postoperative speech processor fitting, but the influence of
      anesthetics on threshold values needs to be taken into account. In a
      retrospective study with 20 patients between 3 and 43 years of age, a highly
      significant correlation between the dosage of methohexital and the mean stapedius
      reflex threshold value could be shown (r = 0.65, p = .002). We conclude that more
      reliable threshold values can be obtained by reducing the dosage of hypnotics to
      achieve a lighter level of hypnosis during stapedius reflex measurement. To
      achieve a light, but still sufficient level of hypnosis, electroencephalographic
      monitoring including automatic interpretation of the complex raw signal should be
      used.

PMID- 14703110
TI  - Is there a double innervation of the tensor tympani muscle in humans?
AB  - The middle ear muscles and their function have not yet been fully explored. The
      statement of Lawrence, for example, that the tensor tympani muscle of humans
      might have a dual innervation has never been proven or disproven. The question is
      of great interest; in our opinion, it represents one of the key questions in the
      putative afferent feedback loop of the middle ear muscles in humans. A light
      microscopic study was performed on 16 tensor tympani muscles taken from 11
      cadavers. Six muscles were taken out in toto and stained according to the
      modified method of Sihler. The remaining 10 muscles were dehydrated and embedded
      in paraffin. In 5 of these muscles, complete transverse serial sections were made
      on a microtome at 7 microm and alternately stained by silver impregnation, S-100
      protein immunohistochemistry, and ferric oxide. In the remaining 5 muscles,
      complete longitudinal serial sections were made at 10 microm. These sections were
      alternately stained by the methods of Cason and Maskar. Neither the surgical
      microscopic investigation nor the light microscopic investigation revealed any
      innervation to the human tensor tympani muscle other than the one arising from
      the mandibular branch of the trigeminal nerve. Our findings, apart from the fact
      that they clearly refute an unproven hypothesis, might represent another small
      step toward understanding the innervation of the tensor tympani muscle.

PMID- 14703111
TI  - In vivo visualization of endolymphatic hydrops in guinea pigs: magnetic resonance
      imaging evaluation at 4.7 tesla.
AB  - In order to find out whether it is possible to visualize experimental
      endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7
      T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early
      manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)
      intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5)
      by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd
      DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The
      surface area of 3 partitions of the cochlea was used to quantify endolymphatic
      hydrops. The fine structure of the 3 partitions of the cochlea was visualized
      with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and
      scala vestibuli. As early as 5 days after endolymphatic sac surgery,
      endolymphatic hydrops started to appear as visualized by MRI and also verified
      with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage
      into the scala media was detected with MRI in 1 ES-damaged animal that had a 60
      dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high
      resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent
      of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of
      membranes can be shown with the assistance of Gd-DTPA-BMA.

PMID- 14703112
TI  - Basal cell adenoma of the sublingual gland.
AB  - Salivary gland tumors constitute about 3% to 4% of all head and neck neoplasms.
      Approximately 80% originate in the parotid gland, and they rarely present in the
      sublingual gland; however, a disproportionately large majority of sublingual
      gland tumors are malignant. Basal cell adenoma is a benign epithelial salivary
      gland tumor that appears to have unique histologic characteristics, different
      from those of mixed tumors, and has a predilection for development in the parotid
      and minor salivary glands. No case has ever been reported as arising from the
      sublingual gland in the otolaryngology literature. We report here a case of a
      middle-aged woman with basal cell adenoma of the sublingual gland. The clinical
      presentation, pathological features, differential diagnosis, and treatment
      options for this relatively rare tumor are discussed.

PMID- 14703113
TI  - Tracheal spindle cell tumor in a child.
AB  - Tracheal tumors in the pediatric population are rare neoplasms that have
      devastating consequences if not evaluated and diagnosed in a timely fashion. As
      illustrated by this case, the tumors typically do not become symptomatic until
      marked airway obstruction occurs, and patients may present with acute respiratory
      distress. Radiologic advances, including 3-D CT tracheal reconstruction, are
      invaluable in the diagnosis of and surgical planning for tracheal neoplasms.

PMID- 14703114
TI  - Magnetic beads (Dynabead) toxicity to endothelial cells at high bead
      concentration: implication for tissue engineering of vascular prosthesis.
AB  - Magnetic beads (Dynabeads) have been used for the purification of endothelial
      cells. One application for this procedure may be for single-stage seeding of
      bypass grafts. The number of endothelial cells (EC) isolated is crucial and
      therefore to increase the number of cells extracted, a higher number of Dynabeads
      per cell may need to be used. The effect of large numbers of CD31 Dynabeads on
      cell proliferation/metabolism is unknown. We undertook this study using CD31
      coated Dynabeads and EC from human umbilical vein. EC were coated at
      concentrations of 4, 10, or 50 beads per cell. The cells were cultured for 6 days
      with control being normal EC. Cellular proliferation was assessed by
      trypsinization of cells and metabolism assessed with an Alamar blue viability
      assay. In a further experiment a compliant polyurethane graft was single-stage
      seeded with both coated Dynabeads and normal EC. The results showed that using a
      higher number of beads per cell resulted in a reduction in cell proliferation and
      a reduction in cell metabolism. The total number of Dynabeads-coated cells in
      culture compared to controls (%) by day 6 were 30.7 +/- 2.56, 41.3 +/- 9.8 and
      59.2 +/- 7.3 for 50, 10, and 4 beads per cell, respectively. The corresponding
      results for Alamar blue were 43.7 +/- 1.2, 61.8 +/- 1.4, and 72.1 +/- 4.3. The
      seeded grafts showed reduced metabolism with the Dynabeads-coated EC. In
      conclusion, high numbers of beads per cell have a late detrimental effect on cell
      proliferation and metabolism. Therefore for single-stage seeding lower numbers of
      Dynabeads will need to be used with resultant reduction in the number of
      available EC.

PMID- 14703115
TI  - Inhibitory effect of a naphthazarin derivative, S64, on heat shock factor (Hsf)
      activation and glutathione status following hypoxia.
AB  - The presence of hypoxic cells in solid tumors has long been considered a problem
      in cancer treatment. Resistance of hypoxic cells to ionizing radiation and
      anticancer drugs has in part been attributed to changes in altered gene
      expression by hypoxia. We previously reported an activation of heat shock factor
      (Hsf) in murine tumor RIF cells following hypoxia and suggested that a subsequent
      accumulation of heat shock protein(s) (Hsp) is likely to contribute to the
      malignant progression of hypoxic tumor cells (Baek et al., 2001). In this study,
      we showed that hypoxia induced a DNA-binding activity of Hsf and activation of
      hsp70 gene expression in colon cancer Clone A cells, and that a naphthazarin
      derivative, S64, significantly inhibited the hypoxia-inducible hsp70 gene
      expression in Clone A cells. We also showed that S64 significantly reduced the
      cellular glutathione levels in this cell line. Considering the proposed effects
      of Hsp and glutathione on radiation and chemotherapy sensitivity, we suggest that
      the inhibitory effects of S64 on Hsf activation and cellular glutathione levels
      have potentially important clinical implications. We believe that the previously
      reported in vitro and in vivo anti-tumor effect of S64 (Song et al., 2000a, 2001)
      might be attributed, at least in part, to its effect on Hsf activation and/or
      glutathione depletion. We also believe that the detailed molecular mechanisms
      underlying the effects of S64 on Hsf and glutathione level following hypoxia
      deserve a more rigorous future study, the results of which could offer novel
      strategy to manipulate the resistance mechanisms of solid tumors.

PMID- 14703116
TI  - Preferential elevation of Prx I and Trx expression in lung cancer cells following
      hypoxia and in human lung cancer tissues.
AB  - Transient/chronic microenvironmental hypoxia that exists within a majority of
      solid tumors has been suggested to have a profound influence on tumor growth and
      therapeutic outcome. Since the functions of novel antioxidant proteins,
      peroxiredoxin I (Prx I) and II, have been implicated in regulating cell
      proliferation, differentiation, and apoptosis, it was of our special interest to
      probe a possible role of Prx I and II in the context of hypoxic tumor
      microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron
      donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated
      the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here
      we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and
      an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10
      human lung cancer and paired normal lung tissues also revealed an elevated
      expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical
      analysis of the lung cancer tissues confirmed an augmented Prx I and Trx
      expression in cancer cells with respect to the parenchymal cells in adjacent
      normal lung tissue. Based on these results, we suggest that the redox changes in
      lung tumor microenvironment could have acted as a trigger for the up-regulation
      of Prx I and Trx in lung cancer cells. Although the clinical significance of our
      finding awaits more rigorous future study, preferential augmentation of the Prx I
      and Trx in lung cancer cells may well represent an attempt of cancer cells to
      manipulate a dynamic redox change in tumor microenvironment in a manner that is
      beneficial for their proliferation and malignant progression.

PMID- 14703117
TI  - Subcellular localization of chromium and nickel in root cells of Allium cepa by
      EELS and ESI.
AB  - The ultrastructural investigation of the root cells of Allium cepa L. exposed to
      two different concentrations of chromium + nickel (Cr+Ni) (10 micromol/L and 100
      micromol/L) revealed that toxic symptoms were induced by increasing heavy metal
      concentration and treatment time. Several significant ultrastructural changes
      were caused by 100 micromol/L Cr+Ni - deposition of electron dense material in
      cell walls; larger vacuolar precipitates surrounded by membranes inside vacuoles;
      increment of disintegrated organelles and high vacuolization in cytoplasm. The
      localization of the precipitates in which the metal ions were detected by
      electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI)
      was investigated. Chromium and nickel were localized in the electron dense
      precipitates of the root cells exposed to only 100 micromol/L Cr+Ni. None were
      found in the root cells exposed to 10 micromol/L Cr+Ni. Higher amounts of Cr+Ni
      were mainly accumulated in the cell walls and vacuoles of the fourth or fifth
      cortical layer.

PMID- 14703118
TI  - Use of human reconstructed epidermis to analyze the regulation of beta-defensin
      hBD-1, hBD-2, and hBD-3 expression in response to LPS.
AB  - Defensins have been identified as key elements of innate immunity against
      microbial infections. In the present study, human beta-defensin-2 (hBD-2) mRNA
      and peptide expression were evaluated by RT-PCR and Western blotting in normal
      human keratinocytes, in function of their stage of differentiation. In
      proliferating, non-differentiating keratinocytes generated in serum-free, low
      calcium medium, a very low hBD-2 mRNA expression was found. A significantly
      higher expression was detected in high-calcium cultivated keratinocytes grown
      either as monolayers or as multilayers under submerged conditions. In an air
      liquid interface culture of keratinocytes, allowing epidermis to be
      reconstructed, hBD-2 mRNA expression level was significantly higher than in the
      other conditions and displayed inter-individual variability as observed in native
      epidermis. The peptide was detected only in reconstructed epidermis. These
      results indicate that hBD-2 gene expression in normal human keratinocytes is
      dependent upon their stage of differentiation. The level of expression of hBD-1
      mRNA was lower and that of hBD-3 was higher than that of hBD-2 in reconstructed
      epidermis. Exposure of reconstructed epidermis to bacterial lipopolysaccharide
      (LPS) resulted in an average 4-fold increase in hBD-2 mRNA 18 h after challenge,
      but not of hBD-1 and hBD-3 gene expression. These results show the selective
      regulation of hBD-2-encoding gene in an organotypic epidermal model, in response
      to LPS. They also provide evidence that in vitro reconstructed epidermis
      represents a useful model for studying regulation of expression of beta-defensins
      after skin challenge with pathogenic microorganisms in conditions as close as
      possible to the in vivo situation.

PMID- 14703119
TI  - Protective effects of green tea polyphenol against reactive oxygen species
      induced oxidative stress in cultured rat calvarial osteoblast.
AB  - The injurious effects of reactive oxygen species on osteoblasts and the potential
      protective role played by green tea polyphenols (GtPP) were investigated using
      primarily cultured rat calvarial osteoblasts. Oxidative stress was induced in
      cultured osteoblasts, either by adding 100 mmol/L H2O2 or by the action of 40 U/L
      xanthine oxidase (XO) in the presence of xanthine (250 micromol/L). After
      incubation, the cellular viability, function and morphology were evaluated. Both
      treatments produced a significant reduction in osteoblast viability, as assessed
      by a two-colored fluorescence staining method combined with flow cytometric
      analysis and MTT assay. A significant reduction in the alkaline phosphatase
      activity was observed after H2O2 addition, whereas XO did not have the same
      effect. On the microscopic observations, the morphological changes and
      intracellular ultrastructural damages were remarkably induced by both treatments.
      The H2O2-induced alterations were prevented by pre-incubating the osteoblasts
      with 200 microg/ml GtPP for 1 h. When the oxidative stress was induced by XO, the
      cellular viability and morphology was also maintained at the same polyphenol
      concentration. These results demonstrate that GtPP can act as a biological
      antioxidant in a cell culture experimental model and protect cells from oxidative
      stress-induced toxicity.

PMID- 14703120
TI  - 3D-QSAR and docking studies on 4-anilinoquinazoline and 4-anilinoquinoline
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
AB  - The overexpression and/or mutation of the epidermal growth factor receptor (EGFR)
      tyrosine kinase has been observed in many human solid tumors, and is under
      intense investigation as a novel anticancer molecular target. Comparative 3D-QSAR
      analyses using different alignments were undertaken employing comparative
      molecular field analysis (CoMFA) and comparative molecular similarity analysis
      (CoMSIA) for 122 anilinoquinazoline and 50 anilinoquinoline inhibitors of EGFR
      kinase. The SYBYL multifit alignment rule was applied to three different
      conformational templates, two obtained from a MacroModel Monte Carlo
      conformational search, and one from the bound conformation of erlotinib in
      complex with EGFR in the X-ray crystal structure. In addition, a flexible ligand
      docking alignment obtained with the GOLD docking program, and a novel flexible
      receptor-guided consensus dynamics alignment obtained with the DISCOVER program
      in the INSIGHTII modeling package were also investigated. 3D-QSAR models with q2
      values up to 0.70 and r2 values up to 0.97 were obtained. Among the 4
      anilinoquinazoline set, the q2 values were similar, but the ability of the
      different conformational models to predict the activities of an external test set
      varied considerably. In this regard, the model derived using the X-ray
      crystallographically determined bioactive conformation of erlotinib afforded the
      best predictive model. Electrostatic, hydrophobic and H-bond donor descriptors
      contributed the most to the QSAR models of the 4-anilinoquinazolines, whereas
      electrostatic, hydrophobic and H-bond acceptor descriptors contributed the most
      to the 4-anilinoquinoline QSAR, particularly the H-bond acceptor descriptor. A
      novel receptor-guided consensus dynamics alignment has also been introduced for
      3D-QSAR studies. This new alignment method may incorporate to some extent ligand
      receptor induced fit effects into 3D-QSAR models.

PMID- 14703121
TI  - Structure-based prediction of free energy changes of binding of PTP1B inhibitors.
AB  - The goals were (1) to understand the driving forces in the binding of small
      molecule inhibitors to the active site of PTP1B and (2) to develop a molecular
      mechanics-based empirical free energy function for compound potency prediction. A
      set of compounds with known activities was docked onto the active site. The
      related energy components and molecular surface areas were calculated. The
      bridging water molecules were identified and their contributions were considered.
      Linear relationships were explored between the above terms and the binding free
      energies of compounds derived based on experimental inhibition constants. We
      found that minimally three terms are required to give rise to a good correlation
      (0.86) with predictive power in five-group cross-validation test (q2 = 0.70). The
      dominant terms are the electrostatic energy and non-electrostatic energy stemming
      from the intra- and intermolecular interactions of solutes and from those of
      bridging water molecules in complexes.

PMID- 14703122
TI  - Benzimidazole derivatives. 4. The recognition of the voluminous substituent
      attached to the basic amino group of 5-HT4 receptor antagonists.
AB  - We report a structure-affinity analysis of an important element in the
      pharmacophore model for the recognition of 5-HT4 receptor antagonists: the
      voluminous substituent attached to the basic nitrogen of the ligand. We have
      designed, synthesized and pharmacologically evaluated a series of benzimidazole
      derivatives 1 containing a common molecular skeleton formed by N-[(4
      piperidyl)methyl]-6-chlorobenzimidazole-4-carboxamide and four different
      substituents (R = butyl, 2-[(methylsulfonyl)amino]ethyl, 5
      [(phenylacetyl)amino]pentyl, and 5-[(benzylsulfonyl)amino]pentyl). These
      compounds possess binding affinities in the nM range (Ki = 0.11-1.50 nM).
      Moreover, a ligand that contains a hydrogen atom attached to the basic nitrogen
      (R = H; Ki = 150 nM) is used as a control for structure-affinity relationships.

PMID- 14703123
TI  - Automated docking of ligands to an artificial active site: augmenting
      crystallographic analysis with computer modeling.
AB  - The W191G cavity of cytochrome c peroxidase is useful as a model system for
      introducing small molecule oxidation in an artificially created cavity. A set of
      small, cyclic, organic cations was previously shown to bind in the buried,
      solvent-filled pocket created by the W191G mutation. We docked these ligands and
      a set of non-binders in the W191G cavity using AutoDock 3.0. For the ligands, we
      compared docking predictions with experimentally determined binding energies and
      X-ray crystal structure complexes. For the ligands, predicted binding energies
      differed from measured values by +/- 0.8 kcal/mol. For most ligands, the docking
      simulation clearly predicted a single binding mode that matched the
      crystallographic binding mode within 1.0 A RMSD. For 2 ligands, where the docking
      procedure yielded an ambiguous result, solutions matching the crystallographic
      result could be obtained by including an additional crystallographically observed
      water molecule in the protein model. For the remaining 2 ligands, docking
      indicated multiple binding modes, consistent with the original electron density,
      suggesting disordered binding of these ligands. Visual inspection of the atomic
      affinity grid maps used in docking calculations revealed two patches of high
      affinity for hydrogen bond donating groups. Multiple solutions are predicted as
      these two sites compete for polar hydrogens in the ligand during the docking
      simulation. Ligands could be distinguished, to some extent, from non-binders
      using a combination of two trends: predicted binding energy and level of
      clustering. In summary, AutoDock 3.0 appears to be useful in predicting key
      structural and energetic features of ligand binding in the W191G cavity.

PMID- 14703125
TI  - A new world order--or more of the same?

PMID- 14703124
TI  - Representation, searching and discovery of patterns of bases in complex RNA
      structures.
AB  - We describe a graph theoretic method designed to perform efficient searches for
      substructural patterns in nucleic acid structural coordinate databases using a
      simplified vectorial representation. Two vectors represent each nucleic acid base
      and the relative positions of bases with respect to one another are described in
      terms of distances between the defined start and end points of the vectors on
      each base. These points comprise the nodes and the distances the edges of a
      graph, and a pattern search can then be performed using a subgraph isomorphism
      algorithm. The minimal representation was designed to facilitate searches for
      complex patterns but was first tested on simple, well-characterised arrangements
      of bases such as base pairs and GNRA-tetraloop receptor interactions. The method
      performed very well for these interaction types. A survey of side-by-side base
      interactions, of which the adenosine platform is the best known example, also
      locates examples of similar base rearrangements that we consider to be important
      in structural regulation. A number of examples were found, with GU platforms
      being particularly prevalent. A GC platform in the RNA of the Thermus
      thermophilus small ribosomal subunit is in an analogous position to an adenosine
      platform in other species. An unusual GG platform is also observed close to one
      of the substrate binding sites in Haloarcula marismortui large ribosomal subunit
      RNA.

PMID- 14703126
TI  - Crisis in the United Nations, NATO and the European Union.
AB  - The unilateralist policies of the United States administration have raised the
      question of how the international system should operate. It is suggested that the
      administration is dismissive of institutions such as the United Nations, the
      International Criminal Court and the Kyoto Protocol because they do not permit
      the US to follow its desire to be the world's unchallenged economic, political
      and military force. It is proposed that the Organization for Security and Co
      operation in Europe should be responsible for European security in place of NATO.
      The European Union should not attempt to compete militarily with the US, but
      could act as a counterweight by adopting sustainable economic policies and
      political reforms. The United Nations must be democratized and international
      security enhanced by dealing with poverty and inequality. An emerging global
      public opinion may provide the political will for this to be achieved.

PMID- 14703127
TI  - Seascape with monkeys and guinea-pigs: Britain's biological weapons research
      programme, 1948-54.
AB  - The British biological weapons (BW) research programme based at Porton Down
      continued after the Second World War. Five series of BW experiments with animals
      at sea were undertaken to supplement laboratory work. The causative organisms for
      plague, brucellosis, tularemia and later Venezuelan equine encephalomyelitis and
      Vaccinia viruses were tested in the Caribbean near Antigua in the late 1940s, in
      Hebridean waters (north-west Scotland) in the early 1950s and off Nassau in the
      Bahamas in 1953-54. In September 1952, at the end of Operation 'Cauldron' off the
      Isle of Lewis, a trawler, the Carella, passed through the danger area when a
      toxic cloud had been released and was covertly watched until the incubation
      period had passed in case those on board had come into contact with the plague
      bacillus. Publicity about the trials was avoided, but a press statement was
      issued in March 1954. The last series provoked sustained agitation in Cuba. More
      recently an outline of the sequence has emerged in the UK parliamentary record
      and in Porton's official history, and a fuller account of the Scottish trials has
      awakened some interest locally.

PMID- 14703128
TI  - The Biological Weapons Convention after November 2002.
AB  - The Fifth Review Conference of the Biological Weapons Convention, in November
      2002, was the first to fail to produce a Final Document. It saw heated debate on
      non-compliance with the spirit of the prohibitions that it enshrines and marked
      the collapse of almost ten years of negotiations attempting to create a Protocol
      to strengthen the Convention. What was to emerge was a new process, very
      different from the traditional tools of arms control. This article examines the
      events that culminated in this drastic new approach, details the nature of this
      new process and discusses the possible short-, medium- and long-term impact of
      these events on the norm against the weaponization of disease.

PMID- 14703129
TI  - Bioterrorism in the United States: a balanced assessment of risk and response.
AB  - There are many definitions of terrorism and numerous examples of the use of
      explosives and small arms, especially against civilians and with the objective of
      instilling fear. Although chemical and biological agents have only rarely been
      used by terrorists, there has recently been much concern about the threat of
      bioterrorism and the role of future health personnel in counteracting it.
      Rational setting of priorities requires the balance of risks against benefits in
      prevention and preparedness. Adverse effects of preparedness include
      inappropriate warnings, diversion of resources from other public health measures,
      both in the United States and overseas and constraints on civil rights. It is
      argued that the US should counteract the threat of bioterrorism by dealing with
      its root causes and by strengthening civil rights, international arms control and
      international law rather than by a self-defeating 'war on terrorism'.

PMID- 14703130
TI  - Which bio-weapons might be used by terrorists against the United Kingdom?
AB  - The properties of potential biological weapon agents for bioterrorism include a
      consistent effect at low dosage and short incubation period in a population of
      low immunity, being difficult to treat, able to be produced in bulk, stable in
      storage and readily disseminated. Possible agents include smallpox, haemorrhagic
      fever viruses, anthrax, tularaemia and plague. The example of Severe Acute
      Respiratory Syndrome (SARS) demonstrates the possible consequences of an act of
      bioterrorism, but also the necessary global response. There is scepticism about
      the practicability of surveillance schemes and the global elimination of
      biological weapons though the Biological and Toxin Weapons Convention remains
      urgent.

PMID- 14703131
TI  - Bioterrorism: how should doctors respond to the threat of biological weapons?
AB  - Planning for the threat of a biological weapons attack includes preparations to
      recognize and identify an attack and its scale. Training is the key element of
      any response, but it is not possible for any health service to maintain
      sufficient extra capacity to deal with a massive bioterrorist threat. Training
      must include both first- and second-line responders. Subject to issues of
      confidentiality, information about plans should be as widely available as
      possible. Planning for prevention is also important. This should include stopping
      the production and dispersal of weapons under international humanitarian law and
      establishing the ethical basis on which doctors and scientists would not become
      involved in the production of biological and other weapons.

PMID- 14703132
TI  - Medical network for social reconstruction in the former Yugoslavia.

PMID- 14703133
TI  - Teramo Declaration.

PMID- 14703134
TI  - Urban drainage and highway runoff in cold climates: conference overview.
AB  - This overview of research findings presented at the conference on urban drainage
      and highway runoff in cold climates starts with generation of urban runoff and
      snowmelt, followed by snowmelt and winter runoff quality, best management
      practices for urban snowmelt and winter runoff, and snow management in urban
      areas. Research on the urban hydrological cycle is lagging behind the needs in
      this field, particularly in terms of data availability. The current studies of
      winter urban runoff quality focus on road salts in the urban environment and
      their environmental effects. The needs for better source controls in salt
      applications, improved management of chloride-laden runoff, and selective
      adoption of environmentally safer alternative de-icers were reported. Adaptation
      of the conventional stormwater best management practices (BMPs) for winter
      operation remains a challenge. The first step in refining the existing BMPs for
      winter operation is to advance the understanding of their operation, as reported
      for some cases at the conference. Finally, snow management in urban areas may
      require local storage of fresh (unpolluted) snow and disposal of more polluted
      snow at central snow disposal sites.

PMID- 14703135
TI  - Review of operation of urban drainage systems in cold weather: water quality
      considerations.
AB  - Cold climate imposes special requirements on urban drainage systems, arising from
      extended storage of precipitation and pollutants in the catchment snowpack,
      processes occurring in the snowpack, and changes in catchment surface and
      transport network by snow and ice. Consequently, the resulting catchment response
      and runoff quantity differ from those experienced in snow- and ice-free seasons.
      Sources of pollutants entering urban snowpacks include airborne fallout, pavement
      and roadside deposits, and applications of de-icing and anti-skid agents. In the
      snowpack, snow, water and chemicals are subject to various processes, which
      affect their movement through the pack and eventual release during the melting
      process. Soluble constituents are flushed from the snowpack early during the
      melt; hydrophobic substances generally stay in the pack until the very end of
      melt and coarse solids with adsorbed pollutants stay on the ground after the melt
      is finished. The impacts of snowmelt on receiving waters have been measured
      mostly by the snowmelt chemical composition and inferences about its
      environmental significance. Recently, snowmelt has been tested by standard
      bioassays and often found toxic. Toxicity was attributed mostly to chloride and
      trace metals, and contributed to reduced diversity of benthic and plant
      communities. Thus, snowmelt and winter runoff discharged from urban drainage
      threaten aquatic ecosystems in many locations and require further studies with
      respect to advancing their understanding and development of best management
      practices.

PMID- 14703136
TI  - Cold climate BMPs: solving the management puzzle.
AB  - Snowmelt runoff and rain-on-snow events present some of the highest pollutant
      loading and most difficult management challenges in the course of a year in
      regions with cold climate. Frozen conduits, thick ice layers, low biological
      activity, altered chemistry, and saturated or frozen ground conditions all work
      against effective treatment of melt runoff. Understanding the source, evolution
      and transition that occurs within a melt event, and defining the management
      objectives for specific receiving waters will help focus the search for effective
      management techniques. Solving the management puzzle means putting together a
      strategy for both soluble and solids-associated water pollutants.

PMID- 14703137
TI  - The effects of de-icing in Helsinki urban streams, southern Finland.
AB  - The environmental effects of road salt have been studied in Finland mainly in
      order to monitor and reduce groundwater contamination. In urban areas the road
      salt used for road maintenance in winter ends up in the storm water drains and
      receiving water bodies. We report here on water samples taken in 1998-1999 from
      three urban streams with catchments varying in area 1.7 to 24.4 km2 in different
      parts of the City of Helsinki. Despite efforts to reduce the amount of road salt,
      high concentrations were found in the urban stream water. Sudden variations in
      water quality were very marked during the spring flood period, with sodium and
      chloride concentrations varying over nine-fold within one day. Some 35-50% of the
      salt used on the roads in Helsinki passes into natural streams and from there
      into the sea. The significant positive correlation between NaCl and dissolved
      zinc in stream water was observed. The results show that it is important to
      monitor water quality, especially at the beginning of the spring flood period,
      when road salt and other contaminant levels are markedly high in urban streams.

PMID- 14703138
TI  - Migration of alternative de-icers in unsaturated zone of aquifers--in vitro
      study.
AB  - The migration of organic de-icers in the shallow aquifers typical in Finland is
      not well known and we need to find solutions to minimise the negative impacts of
      de-icing on groundwater quality. The objective of the MIDAS project is to find de
      icers which have the least harmful impacts on groundwater quality. Migration of
      sodium chloride as a tracer and five alternative de-icers in aquifers was
      studied. The alternative de-icers were calcium chloride, magnesium chloride,
      calcium-magnesium-acetate, potassium acetate and potassium formate. The research
      consists of leaching of heavy metals from roadsides in the area of Highway 1 in
      southern Finland; an in vitro study, which represented the full length of winter
      at low temperatures; and the subsequent on-going field research in south-eastern
      Finland. So far, in our studies potassium formate caused fewer changes to the
      quality of the infiltrated water than the chlorides and acetates. After finishing
      the on-going research the results will be used to choose a preferred de-icer from
      the existing chemicals and for the development of new less harmful de-icers. The
      information will be used mainly in Scandinavia and North America where the
      hydrogeological conditions are similar to those in Finland.

PMID- 14703139
TI  - Increased chloride concentration in a lake due to deicing salt application.
AB  - During winter, the Swedish National Road Administration uses on average 250,000
      tonnes of sodium chloride for deicing purposes. Chloride concentration is a
      function of the amount of deicing salt applied during the winter season and the
      amount of water in which the salt can be diluted. An estimation of seasonal
      amount of deicing salt in relation to amount of run-off was used in order to
      identify the effects of deicing salt. The measured chloride concentration in a
      lake used as a municipal water supply was similar to the concentration estimated
      by a simple steady state method accounting for the catchment area. The simplified
      steady state method was a useful tool for estimating steady state concentrations
      on a regional level, including a non-influenced lake as a comparison.

PMID- 14703140
TI  - Road salts in urban stormwater: an emerging issue in stormwater management in
      cold climates.
AB  - Potential impacts of road salting on the environment have increased by the
      introduction of certain stormwater management practices. Specific impacts are
      discussed for four such practices, infiltration facilities, oil and grit
      separators, stormwater ponds and constructed wetlands. The main concerns about
      the hazards of chloride-laden stormwater discharges include contamination of
      groundwater, leaching out of trace metals, densimetric stratification and poor
      vertical mixing in ponds, direct and indirect toxic effects, benthic drift and
      reduced biodiversity. The associated environmental risks need to be reduced by
      chloride source controls, and prevention of excessive chloride accumulations by
      appropriate design and operation of stormwater facilities in winter months.

PMID- 14703141
TI  - Comparison of the effects of using local and central snow deposits: a case study
      in Lulea.
AB  - The aim of the study was to determine if an increased use of local land-based
      snow deposits would be more sustainable than the use of a central snow deposit.
      The study focused on transport related emissions, costs for transporting the
      snow, technical attendance, local effects, public acceptance, land use, effects
      on the recipient environmental control and potential for accidents. General
      information was obtained from an inventory regarding snow handling that was made
      in 14, geographically spread, Swedish municipalities during 2001. The comparison
      of costs for transporting snow and transport-related emissions was based on
      information gathered from the municipality of Lulea. The study showed that using
      local land-based snow deposits would decrease traffic-related emissions such as
      CO2, CO and NO(x) by 40% annually and would decrease the annual cost for
      transporting snow by nearly 80%. On the other hand local snow deposits may lead
      to an increased risk of accidents and to negative local effects such as delayed
      growing season, flooding and drainage problems. Available land for local snow
      deposits in the cities is hard to find, and is usually expensive. Therefore a
      combination of local and central snow deposits is likely to be the most realistic
      option.

PMID- 14703142
TI  - Siting, design and operational controls for snow disposal sites.
AB  - The Municipality of Anchorage (MOA), at 61 degrees north latitude, ploughs and
      hauls snow from urban streets throughout the winter, incorporating grit and
      chloride applied to street surfaces for traffic safety. Hauled snow is stored at
      snow disposal facilities, where it melts at ambient spring temperatures. MOA
      studies performed from 1998 through 2001 show that disposal site melt processes
      can be manipulated, through site design and operation practices, to control
      chloride and turbidity in meltwater. An experimental passive "V-swale" pad
      configuration tested by MOA investigators reduced site meltwater turbidity by an
      order of magnitude (to about 50 NTU from the 500 NTU typical of more conventional
      planar pad geometry). The MOA has developed new siting, design and operational
      criteria for snow disposal facilities to conform to the tested V-swale pad
      configuration.

PMID- 14703143
TI  - Seasonal variations in road runoff quality in Lulea, Sweden.
AB  - In regions with cold climate the urban drainage and highway runoff processes
      become much more complex, compared to temperate regions. Therefore, climatic
      conditions should be taken into account in planning and design of BMPs and snow
      handling strategies. In order to increase the knowledge of road runoff quality
      during melt and rain periods, respectively, measurements were carried out at a
      field site during a two-month period. The field site was situated at Sodra
      Hamnleden, a road with 7,400 vehicles/day, in the central part of Lulea. Runoff
      samples were analysed for suspended solids and heavy metals (Pb, Cu, Cd, Ni and
      Zn). The results showed that the concentrations of suspended solids, lead, copper
      and cadmium were higher for the melt period, compared to rain generated runoff on
      the catchment without snow, and the highest concentrations were found during the
      rain-on-snow events. The results indicate a flow dependent increase in the
      concentration of suspended solids during the melt period. A comparison of the
      total mass of suspended solids over a one-month period showed that the melt
      period produced about 3 times more suspended solids. Metal elements during melt
      period were more particulate bound as compared to the rain period characterised
      by a higher percentage of the dissolved fraction.

PMID- 14703144
TI  - Low temperature biodegradation of airport de-icing fluids.
AB  - The biodegradabilities of glycol- and acetate-based aircraft de-icing fluids on
      airport surfaces have been investigated at three temperatures between 0 degrees C
      and 10 degrees C. The aqueous solubilities of these substances can result in high
      BOD loadings in runoff and pose serious toxicity problems in receiving waters.
      The measured surface biodegradation rates for de-icing products based on
      ethylene/diethylene glycol (Konsin), propylene glycol (Kilfrost) and potassium
      acetate (Clearway) at 4 degrees C were 0.082, 0.073 and 0.033 day(-1). The
      resulting reductions in the potential BOD loadings, of a single application of a
      typical mixture of these products, over a 5 day biodegradation period are
      predicted to be 32.9%, 30.2% and 21.4%, respectively at 8 degrees C, 4 degrees C
      and 1 degrees C. For consecutive daily applications, the comparable cumulative
      reductions over 5 days are 20.8%, 18.9% and 13.3%. The subsequent savings in the
      amount of treatment required for airport runoff prior to safe discharge to
      receiving waters are discussed and hence the relevance of surface biodegradation
      processes to the design of stormwater treatment systems involving the wash-off of
      biodegradable pollutants following retention on urban surfaces.

PMID- 14703145
TI  - Facilities for treatment of stormwater runoff from highways.
AB  - Stormwater is the major water inflow to many water bodies in Stockholm. Stockholm
      City has adopted a strategy, which defines the need to treat different kinds of
      stormwater entering different receiving waters. The Stockholm Water Company has
      tested various ways of treating stormwater. In 2000, the City of Stockholm
      arranged a stormwater treatment technology competition. Prizes were awarded to
      four winning entries. One installation was completed in 2001 and another is now
      under construction.

PMID- 14703146
TI  - Grassed swales for stormwater pollution control during rain and snowmelt.
AB  - The retention of suspended solids, particles and heavy metals in different
      grassed swales during rain events and snowmelt is discussed. The experimental
      results derived from investigations performed in existing grassed swales in the
      Lulea region, Northern Sweden. During high pollutant loading rates, grassed
      swales retain significant amounts of pollutants, mainly due to sedimentation of
      particulate matter. Low to moderate removal efficiencies could be expected for
      heavy metals, especially metals in solution (i.e. the dissolved phase). When
      grassed swales receive urban runoff with low pollutant concentrations, they may
      release rather than retain pollutants. Swales are important snow deposit areas in
      the city and particle bound pollutants do to a large extent remain in the swale
      after snowmelt. However, dissolved pollutants (i.e. dissolved heavy metals) are
      likely to escape the swale with the melt water. Grassed swales may be regarded as
      facilities that even out the peaks in pollutant loads without being capable of
      producing consistent high removal rates. This suggests that swales should be
      considered as primary treatment devices. Possible design parameters for grassed
      swales are mean hydraulic detention time, surface loading rate or specific swale
      area.

PMID- 14703147
TI  - Winter operation of an on-stream stormwater management pond.
AB  - The winter operation of an on-stream stormwater management pond in Kingston,
      Canada is characterised. The pond froze over in late November. Ice thickness
      varied from 0.2 to 0.5 m, and initially, was well described by Stefan's formula.
      The measured and modelled velocity field indicated a fast flow region, a small
      dead zone and a large recirculating zone. During a snowmelt event, near-bottom
      velocities reached 0.05 m x s(-1), but were not sufficient to scour the bottom
      sediment. Pond water temperature increased with depth, from 0.5 degrees C to 3.5
      degrees C. The dissolved oxygen (DO) levels observed in the pond (6-13 mg x L(
      1)) indicated stable aerobic conditions at the sediment-water interface. In one
      brief episode, DO fell to zero after a long cold spell. Reduction in DO readings
      from inlet to outlet indicated an oxygen consumption of about 1.7 kg x day(-1).
      pH ranged from 7.1 to 8.9. Conductivity readings indicated large quantities of
      total dissolved solids, representing mostly chloride from de-icing agents. During
      baseflow, conductivity increased with depth (total dissolved solids
      concentrations up to 1,200 mg x L(-1) near the bottom), indicating density
      stratification. Average trace metal concentrations were mostly below detection
      limits.

PMID- 14703148
TI  - Modelling of temperature effects on removal efficiency and dissolved oxygen
      concentrations in stormwater ponds.
AB  - The performance of stormwater ponds, operated under winter conditions, was
      modelled using the commercial software Mike21 and MOUSE. Direct and indirect
      effects of changing temperature were investigated. The most important effect of
      winter conditions is the changed hydrology, characterised by long periods with no
      runoff followed by snowmelt events with large runoff volumes during several days.
      This gives lower removal efficiencies than during a period with the same
      precipitation but without winter conditions. For the concentration of dissolved
      oxygen, wind is an important factor. Consequently the most important effect of an
      ice cover on the pond is that it prevents the oxygenation effects of the wind.
      The direct temperature effects on the removal processes are negligible compared
      to the indirect effects in changed hydrology and forming of ice cover.

PMID- 14703149
TI  - Estimation of snow covered area for an urban catchment using image processing and
      neural networks.
AB  - This paper presents a method to estimate the snow covered area (SCA) for small
      urban catchments. The method uses images taken with a digital camera positioned
      on top of a tall building. The camera is stationary and takes overview images of
      the same area every fifteen minutes throughout the winter season. The images were
      read into an image-processing program and a three-layered feed-forward perceptron
      artificial neural network (ANN) was used to calculate fractional snow cover
      within three different land cover types (road, park and roofs). The SCA was
      estimated from the number of pixels with snow cover relative to the total number
      of pixels. The method was tested for a small urban catchment, Risvollan in
      Trondheim, Norway. A time series of images taken during spring of 2001 and the
      2001-2002 winter season was used to generate a time series of SCA. Snow covered
      area was also estimated from aerial photos. The results showed a strong
      correlation between SCA estimated from the digital camera and the aerial photos.
      The time series of SCA can be used for verification of urban snowmelt models.

PMID- 14703150
TI  - Response surfaces for climate change impact assessments in urban areas.
AB  - Assessment of the impacts of climate change in real-world water systems, such as
      urban drainage networks, is a research priority for IPCC (Intergovernmental Panel
      of Climate Change). The usual approach is to force a hydrological transformation
      model with a changed climate scenario. To tackle uncertainty, the model should be
      run with at least high, middle and low change scenarios. This paper shows the
      value of response surfaces for displaying multiple simulated responses to
      incremental changes in air temperature and precipitation. The example given is
      inflow, related to sewer infiltration, at the Lycksele waste water treatment
      plant. The range of plausible changes in inflow is displayed for a series of runs
      for eight GCMs (Global Circulation Model; ACACIA; Carter, 2002, pers. comm.).
      These runs are summarised by climate envelopes, one for each prediction time
      slice (2020, 2050, 2080). Together, the climate envelopes and response surfaces
      allow uncertainty to be easily seen. Winter inflows are currently sensitive to
      temperature, but if average temperature rises to above zero, inflow will be most
      sensitive to precipitation. Spring inflows are sensitive to changes in winter
      snow accumulation and melt. Inflow responses are highly dependent on the
      greenhouse gas emission scenario and GCM chosen.

PMID- 14703151
TI  - Are Kuwaitis getting fatter?
AB  - The purpose of the study is to compare temporal changes in BMI, overweight (BMI >
      25 Kg/m2) and obesity (BMI > 30 Kg/m2) of two independent cross-sectional samples
      of Kuwaitis studied in 1980-81 and 1993-94. The earlier sample of 2067 (896 men
      and 1171 women) and the latter sample of 3435 (1730 men and 1705 women) adult
      Kuwaitis (aged > or = 18 years), were drawn from primary health care (PHC)
      clinics and studied for nutritional assessment and for prevalence of obesity in
      1980-81 and 1993-94, respectively. Weight was measured in kilograms and height in
      meters to obtain the body mass index (BMI), which is the weight in kilograms
      divided by the height in meters squared (Kg/m2). BMI > 25 and > 30 Kg/m2 were
      classified as overweight and obesity, respectively. The results of the study show
      that mean BMI (Kg/m2) increased significantly (p < 0.001) by 10.0 and 6.2% (2.5
      and 1.7 Kg/m2) among men and women, respectively. Prevalence of overweight and
      obesity (BMI > 25 and > 30 Kg/m2) increased by 20.6 and 15.4% and by 13.7 and
      8.4% among men and women, respectively. After controlling for sociodemographic
      differences between the two study periods, mean BMI was 2.0 and 1.6 Kg/m2 higher
      in 1993-94 than in 1980-81 among men and women, respectively. Prevalence of
      overweight and obesity (BMI > 25 and > 30 Kg/m2) also increased among both
      genders between the two periods (OR = 2.1 , 95% CI 1.7-2.7 and OR = 1.9, 95% CI
      1.5-2.4, for men and OR = 2.2, 95% CI 1.6-3.0 and OR = 1.4, 95% CI 2.2 CI 1.0
      1.9, for women). It can be concluded that the BMI, prevalence of overweight and
      obesity increased among Kuwaitis between 1980-81 and 1993-94, probably due to the
      effects of modernization, affluence, increased food consumption and the
      concomitant changes to sedentary lifestyles. The rate of temporal changes in BMI
      and obesity were higher, by comparison, in Kuwait than in selected other
      countries.

PMID- 14703152
TI  - School children: their health and the challenge.

PMID- 14703153
TI  - Obesity, diabetes and other problems.

PMID- 14703154
TI  - Nutrition and schizophrenia: an epidemiological and clinical perspective.
AB  - There is well accepted evidence that the long-term outcome of schizophrenia is
      better in developing than in developed countries. Socio-cultural factors, which
      are as yet unidentified, have been postulated to explain this. There is also
      disputed evidence that schizophrenia was rare in indigenous populations and
      increased when they came into contact with Western or industrialised cultures,
      and that there was an increase in the rate of schizophrenia during the Industrial
      Revolution. These epidemiological and historical findings point to diet as a
      possible mediating factor in schizophrenia. Ecological studies have indicated
      that a worse outcome of schizophrenia is associated with higher consumption of
      saturated fat and sugar. It is also known that schizophrenic patients have
      increased insulin resistance and are at increased risk of developing diabetes and
      coronary heart disease. These findings suggest a new paradigm for our
      understanding of the causation and treatment of schizophrenia.

PMID- 14703155
TI  - Antioxidant status of adult Nigerian asthmatics: implications for prognosis.
AB  - Serum antioxidant status of 50 (19M, 31F) adult asthmatic patients, aged 40 to 50
      yr and attending the medical outpatient clinic of the University College
      Hospital, Ibadan, has been assessed, by measurement of serum ascorbic acid,
      copper, zinc, albumin, uric acid and magnesium levels, to determine the
      relationship between antioxidant status and severity of bronchial asthma. Twenty
      five (25) age matched adults (10M, 15F) served as controls. The test subjects
      were classified into two groups (1&2) based on the degree of respiratory
      distress. Questionnaires were also used to obtain data on subjects' fruit and
      vegetable intake. Fruit and vegetable intake was similar in patients and
      controls, 96% and 100% respectively reporting adequate intake. Copper (Cu) level
      was not significantly different between patients and control subjects, but was
      significantly higher in female asthmatics than in males (p < 0.05). Magnesium
      (Mg) level was also lower in asthmatics than in control subject (p < 0.001).
      Plasma Zinc level was not different between patients and control (p > 0.05). The
      levels of the other antioxidants, vitamin C, uric acid and albumin were all lower
      in asthmatics than in controls (p < 0.05, p < 0.001, p < 0.001) respectively. The
      magnesium level of group 2 (severe asthmatics) was lower than in controls (p <
      0.05) unlike moderate asthmatics (group 1) which do not differ significantly from
      controls. These findings support the emerging concept that antioxidants are
      consumed in this inflammatory disease and that a corresponding increase in
      antioxidant supply may improve prognosis for bronchial asthma.

PMID- 14703156
TI  - Mothers' beliefs and attitudes towards child weight, child feeding and related
      practices in Myanmar.
AB  - The aim is to identify mother's attitude and concern regarding child weight and
      feeding practices and also to explore the importance of growth monitoring
      activity in preventing Protein, Energy. Malnutrition (PEM). Trained interviewers
      from the respective State/Division nutrition team interviewed ninety mothers from
      different areas and Divisions. Mothers were categorized into three groups of
      thirty: those with a well-nourished child, a malnourished child or a child who
      had died of infectious disease. 90% of well-nourished children were weighed at
      birth and 100% of them had received regular weighing. 89% of their mothers could
      identify their child birth weight as normal and all of them know the negative
      health consequences of Low Birth Weight. Regarding attitude towards feeding
      during illness, most mothers of a well-nourished child believe that feeding
      during illness is better for recovery. That proportion is high as twice as of the
      remaining groups. Data regarding child feeding practices show mothers of a well
      nourished child have timely and appropriate starting of these practices. It is
      inferred from the recent finding that mothers who had received growth monitoring
      program since delivery have better preventive behavior for PEM and the role of
      basic health staff in these activity is also acknowledged.

PMID- 14703157
TI  - The place of oats in Scottish nutrition.

PMID- 14703158
TI  - Indigestion and coeliac disease.

PMID- 14703159
TI  - Exact helical reconstruction using native cone-beam geometries.
AB  - This paper is about helical cone-beam reconstruction using the exact filtered
      backprojection formula recently suggested by Katsevich (2002a Phys. Med. Biol. 47
      2583-97). We investigate how to efficiently and accurately implement Katsevich's
      formula for direct reconstruction from helical cone-beam data measured in two
      native geometries. The first geometry is the curved detector geometry of third
      generation multi-slice CT scanners, and the second geometry is the flat detector
      geometry of C-arms systems and of most industrial cone-beam CT scanners. For each
      of these two geometries, we determine processing steps to be applied to the
      measured data such that the final outcome is an implementation of the Katsevich
      formula. These steps are first described using continuous-form equations,
      disregarding the finite detector resolution and the source position sampling.
      Next, techniques are presented for implementation of these steps with finite data
      sampling. The performance of these techniques is illustrated for the curved
      detector geometry of third-generation CT scanners, with 32, 64 and 128 detector
      rows. In each case, resolution and noise measurements are given along with
      reconstructions of the FORBILD thorax phantom.

PMID- 14703160
TI  - Rank-shaping regularization of exponential spectral analysis for application to
      functional parametric mapping.
AB  - Compartmental models are widely used for the mathematical modelling of dynamic
      studies acquired with positron emission tomography (PET). The numerical problem
      involves the estimation of a sum of decaying real exponentials convolved with an
      input function. In exponential spectral analysis (SA), the nonlinear estimation
      of the exponential functions is replaced by the linear estimation of the
      coefficients of a predefined set of exponential basis functions. This set-up
      guarantees fast estimation and attainment of the global optimum. SA, however, is
      hampered by high sensitivity to noise and, because of the positivity constraints
      implemented in the algorithm, cannot be extended to reference region modelling.
      In this paper, SA limitations are addressed by a new rank-shaping (RS) estimator
      that defines an appropriate regularization over an unconstrained least-squares
      solution obtained through singular value decomposition of the exponential base.
      Shrinkage parameters are conditioned on the expected signal-to-noise ratio.
      Through application to simulated and real datasets, it is shown that RS
      ameliorates and extends SA properties in the case of the production of functional
      parametric maps from PET studies.

PMID- 14703161
TI  - Is patient size important in dose determination and optimization in cardiology?
AB  - Patient dose determination and optimization have become more topical in recent
      years with the implementation of the Medical Exposures Directive into national
      legislation, the Ionising Radiation (Medical Exposure) Regulations. This
      legislation incorporates a requirement for new equipment to provide a means of
      displaying a measure of patient exposure and introduces the concept of diagnostic
      reference levels. It is normally assumed that patient dose is governed largely by
      patient size; however, in cardiology, where procedures are often very complex,
      the significance of patient size is less well understood. This study considers
      over 9000 cardiology procedures, undertaken throughout the north of England, and
      investigates the relationship between patient size and dose. It uses simple
      linear regression to calculate both correlation coefficients and significance
      levels for data sorted by both room and individual clinician for the four most
      common examinations, left ventrical and/or coronary angiography, single vessel
      stent insertion and single vessel angioplasty. This paper concludes that the
      correlation between patient size and dose is weak for the procedures considered.
      It also illustrates the use of an existing method for removing the effect of
      patient size from dose survey data. This allows typical doses and, therefore,
      reference levels to be defined for the purposes of dose optimization.

PMID- 14703162
TI  - Dual photon absorptiometry using a gadolinium-153 source applied to measure
      equine bone mineral content.
AB  - The application of the dual photon absorptiometry (DPA) technique, using
      gadolinium-153 as the photon source, to evaluate the bone mineral density (BMD)
      of the third metacarpal bone of horses is presented. The radiation detector was
      implemented with a NaI(TI) scintillator coupled to a 14 stage photomultiplier. A
      modular mechanical system allows the position of the prototype to be adjusted in
      relation to the animal. A moveable carrier makes it possible to scan the third
      metacarpal with a velocity adjustable between 1 and 12 mm s(-1), in steps of 1 mm
      s(-1), for a total distance of 250 mm. The prototype was evaluated with a phantom
      of the third metacarpal bone made of perspex and aluminium, and in vitro with a
      transverse slice of the third metacarpal bone of a horse. The tests showed that
      the prototype has an accuracy and precision of, approximately, 10% and 6%,
      respectively, for a 6 s acquisition time. Preliminary studies carried out in
      three foals from birth to one year of age indicated that the prototype is well
      suited to in vivo and in situ analysis of the BMD of the third metacarpal bones
      of horses, making it possible to evaluate the changes of BMD levels on a monthly
      basis. Also, results indicated an exponential behaviour of the BMD curve during
      the first year of life of the studied horses.

PMID- 14703163
TI  - Using Monte Carlo simulations to commission photon beam output factors--a
      feasibility study.
AB  - This study investigates the feasibility of using Monte Carlo methods to assist
      the commissioning of photon beam output factors from a medical accelerator. The
      Monte Carlo code, BEAMnrc, was used to model 6 MV and 18 MV photon beams from a
      Varian linear accelerator. When excellent agreements were obtained between the
      Monte Carlo simulated and measured dose distributions in a water phantom, the
      entire geometry including the accelerator head and the water phantom was
      simulated to calculate the relative output factors. Simulated output factors were
      compared with measured data, which consist of a typical commission dataset for
      the output factors. The measurements were done using an ionization chamber in a
      water phantom at a depth of 10 cm with a source-detector distance of 100 cm.
      Square fields and rectangular fields with widths and lengths ranging from 4 cm to
      40 cm were studied. The result shows a very good agreement (< 1.5%) between the
      Monte Carlo calculated and the measured relative output factors for a typical
      commissioning dataset. The Monte Carlo calculated backscatter factors to the beam
      monitor chamber agree well with measured data in the literature. Monte Carlo
      simulations have also been shown to be able to accurately predict the collimator
      exchange effect and its component for rectangular fields. The information
      obtained is also useful to develop an algorithm for accurate beam modelling. This
      investigation indicates that Monte Carlo methods can be used to assist
      commissioning of output factors for photon beams.

PMID- 14703164
TI  - Multiple-image radiography.
AB  - Conventional radiography produces a single image of an object by measuring the
      attenuation of an x-ray beam passing through it. When imaging weakly absorbing
      tissues, x-ray attenuation may be a suboptimal signature of disease-related
      information. In this paper we describe a new phase-sensitive imaging method,
      called multiple-image radiography (MIR), which is an improvement on a prior
      technique called diffraction-enhanced imaging (DEI). This paper elaborates on our
      initial presentation of the idea in Wernick et al (2002 Proc. Int. Symp. Biomed.
      Imaging pp 129-32). MIR simultaneously produces several images from a set of
      measurements made with a single x-ray beam. Specifically, MIR yields three images
      depicting separately the effects of refraction, ultra-small-angle scatter and
      attenuation by the object. All three images have good contrast, in part because
      they are virtually immune from degradation due to scatter at higher angles. MIR
      also yields a very comprehensive object description, consisting of the angular
      intensity spectrum of a transmitted x-ray beam at every image pixel, within a
      narrow angular range. Our experiments are based on data acquired using a
      synchrotron light source; however, in preparation for more practical
      implementations using conventional x-ray sources, we develop and evaluate
      algorithms designed for Poisson noise, which is characteristic of photon-limited
      imaging. The results suggest that MIR is capable of operating at low photon count
      levels, therefore the method shows promise for use with conventional x-ray
      sources. The results also show that, in addition to producing new types of object
      descriptions, MIR produces substantially more accurate images than its
      predecessor, DEI. MIR results are shown in the form of planar images of a phantom
      and a biological specimen. A preliminary demonstration of the use of MIR for
      computed tomography is also presented.

PMID- 14703165
TI  - Time-series observation of the spreading out of microvessel endothelial cells
      with atomic force microscopy.
AB  - The spreading out of microvessel endothelial cells plays a key role in
      angiogenesis and the post-injury healing of endothelial cells. In our study, a
      physical force applied with an atomic force microscopic (AFM) cantilever tip in
      contact mode partly broke the peripheral adhesion that just-confluent cultured
      rat cerebral microvessel endothelial cells had formed with basal structures and
      resulted in the cells actively withdrawing from the stimulated area. Time-series
      changes in cell extension were imaged using tapping mode AFM, in conjunction with
      total internal reflection fluorescence microscopy, intensified charge-coupled
      device and field emission scanning electron microscopy. We also interpreted phase
      images of living endothelial cells. The results showed that formation of a
      fibronectin molecule monolayer is key to the spreading out of the cells.
      Lamellipods as well as filopods would spread out in temporal and spatial
      distribution following the formation of fibronectin layer. In addition, a lattice
      like meshwork of filopods formed in the regions leading lamellipods, which would
      possibly provide a fulcrum for the filaments of the cytoskeleton within the
      leading cell body periphery.

PMID- 14703166
TI  - Assessment of specific energy absorption rate (SAR) in the head from a TETRA
      handset.
AB  - Finite-difference time-domain (FDTD) calculations of the specific energy
      absorption rate (SAR) from a representative TETRA handset have been performed in
      an anatomically realistic model of the head. TETRA (Terrestrial Trunked Radio) is
      a modern digital private mobile radio system designed to meet the requirements of
      professional users, such as the police and fire brigade. The current frequency
      allocations in the UK are 380-385 MHz and 390-395 MHz for the public sector
      network. A comprehensive set of calculations of SAR in the head was performed for
      positions of the handset in front of the face and at both sides of the head. The
      representative TETRA handset considered. operating at 1 W in normal use, will
      show compliance with both the ICNIRP occupational and public exposure
      restrictions. The handset with a monopole antenna operating at 3 W in normal use
      will show compliance with both the ICNIRP occupational and public exposure
      restrictions. The handset with a helical antenna operating at 3 W in normal use
      will show compliance with the ICNIRP occupational exposure restriction but will
      be over the public exposure restriction by up to approximately 50% if kept in the
      position of maximum SAR for 6 min continuously.

PMID- 14703167
TI  - Conversion of dose-volume constraints to dose limits.
AB  - The purpose of this study is to introduce two techniques for converting dose
      volume constraints to dose limits for treatment planning optimization, and to
      evaluate their performance. The first technique, called dose-sorting, is based on
      the assumption that higher dose limits should be assigned to the constraint
      points receiving higher doses, and vice versa. The second technique, the hybrid
      technique, is a hybrid of the dose-sorting technique and the mixed integer linear
      programming (MILP) technique. Among all constraint points in an organ at risk,
      the dose limits for the points far from a dose-volume constraint are determined
      by dose-sorting, while the dose limits for the points close to a dose-volume
      constraint are determined by MILP. We evaluated the performance of the two new
      techniques for one treatment geometry by comparing them with the MILP technique.
      The dose-sorting technique had a high probability of finding the global optimum
      when no more than three organs at risk have dose-volume constraints. It was much
      faster than the MILP technique. The hybrid technique always found the global
      optimum when the MILP percentage (the percentage of constraint points for which
      the dose limits are determined by the MILP technique) was large enough, but its
      computation time increased dramatically with the MILP percentage. In conclusion,
      the dose-sorting technique and the hybrid technique with a low MILP percentage
      are clinically feasible.

PMID- 14703168
TI  - Computational assessment of improved cell-kill by gadolinium-supplemented boron
      neutron capture therapy.
AB  - Potential improvement in neutron capture therapy (NCT) by utilizing both 157Gd
      and 10B is assessed considering two parameters calculated in transport models in
      MCNP4B, the dose to quiescent cells and the therapeutic ratio. Improved
      sterilization of quiescent or more generally non-uptaking cells is demonstrated
      with the addition of 157Gd to conventional 10B loading. The improved dose
      delivery to non-uptaking cells from concurrent administration of 157Gd and 10B is
      weighed against a second index, degradation in the therapeutic ratio resulting
      from the longer interaction lengths of the 157Gd capture products. Optimal
      concentrations of 157Gd are determined considering varying assumptions for boron
      uptake levels and selectivity. By analysing the dosimetry results of varying
      157Gd concentrations applied concurrently with BPA-delivered boron in NCT, this
      work seeks to determine a balance between the high tumour-specific dose provided
      by BPA and the high dose to quiescent cells provided by potential gadolinium
      agents. Depending upon the assumptions for drug specificity, tumour size and
      fraction of quiescent cells, NCT with low levels of 157Gd (125 microg g(-1))
      supplementing 10B loadings was shown to be superior to treatments applying 10B
      alone.

PMID- 14703169
TI  - Influence of the non-homogeneity of Ir-192 wires in calibration of well chambers.
AB  - All international recommendations point out as necessary the calibration or
      verification of the reference air kerma rate (RAKR) for brachytherapy sources
      (independent of manufacturer established value) prior to their clinical use. The
      most common procedure for RAKR measurement in iridium wires is based on the use
      of well chambers with specific inserts that set the wire in a fixed position;
      previously, the electrometer plus well chamber with insert (EWI) was calibrated
      by using a source obtained from an accredited laboratory for which the RKAR was
      established precisely, called the 'reference' source. The distribution of Ir-192
      material in the wire could be not perfectly homogeneous all along its length, and
      in this case the influence of these inhomogeneities in the calibration process
      should be studied. This paper focuses on the evaluation of this topic and an
      analytical and experimental study is presented taking into account the non
      homogeneity of Ir-192 material along the wire for both the reference source (of
      length 14 cm) and a wire of unknown RAKR. This study is based on measurements
      with a 1 cm iridium wire on a rectilinear insert considering either of the two
      available reference sources (1 or 14 cm length), and has been experimentally
      evaluated using two typical well chambers. The main conclusion of the study is
      that if the non-homogeneity of the wires is lower than 5% the effect of non
      homogeneity on RAKR measurements is negligible for rectilinear inserts even for
      short well chambers.

PMID- 14703170
TI  - Diffusion coefficient for photon transport in turbid media.
AB  - Light propagation in a turbid medium is considered using the linear transport
      equation. The existence of a diffusion length is proved for the Henyey-Greenstein
      scattering kernel for all absorption ratios. Numerical methods are given that
      allow accurate computation of the diffusion coefficient quite easily.

PMID- 14703171
TI  - Source and detector polarization effects on radiographic film dosimetry.
AB  - Kodak X-Omat V radiographic film has been tested for its polarization properties
      when using polarized and non-polarized light sources and detectors. The
      radiographic film has been shown to produce a relatively small but not negligible
      (less than 5%) variation in 90 degrees cycles in measured optical density within
      the visible spectrum when the light source is fully linear polarized and the film
      is rotated through 360 degrees angle. Negligible variations are seen when the
      detector is linearly polarized. If both light source and detector are linearly
      polarized, variations in measured optical density can reach 35% when the film is
      rotated through 360 degrees angle. This seems to be due to variations in the
      degree and axis of rotation in polarized light caused by the radiographic film
      and is independent of exposure level as the intensity of variation in absolute
      optical density is relatively the same for all film exposures. We recommend that
      a polarization test be performed on a densitometry system to establish the extent
      of its polarization properties before accurate dosimetry is performed with
      radiographic film.

PMID- 14703172
TI  - Use of an in-field-of-view shield to improve count rate performance of the single
      crystal layer high-resolution research tomograph PET scanner for small animal
      brain scans.
AB  - The count rate performance of the single LSO crystal layer high-resolution
      research tomograph (HRRT-S) PET scanner is limited by the processing speed of its
      electronics. Therefore, the feasibility of using an in-field-of-view (in-FOV)
      shield to improve the noise equivalent count rates (NECR) for small animal brain
      studies was investigated. The in-FOV shield consists of a lead tube of 12 cm
      length, 6 cm inner diameter and 9 mm wall thickness. It is large enough to shield
      the activity in the body of a rat or mouse. First, the effect of this shield on
      NECR was studied. Secondly, a number of experiments were performed to assess the
      effects of the shield on the accuracy of transmission scan data and, next, on
      reconstructed activity distribution in the brain. For activities below 150 MBq
      NECR improved only by 5-10%. For higher activities NECR maxima of 1.2E4 cps at
      200 MBq and 2.2E4 cps at 370 MBq were found without and with shield,
      respectively. Listmode data taken without shield, however, were corrupted for
      activities above 75 MBq due to data overrun problems (time tag losses) of the
      electronics. When the shield was used data overrun was avoided up to activities
      of 150 MBq. For the unshielded part of the phantom, transmission scan data were
      the same with and without shield. The estimated scatter contribution was
      approximately 8.5% without and 5.5% with shield. Reconstructed emission data
      showed a difference up to 5% in the unshielded part of the phantom at 5 mm or
      more from the edge of the shielding. Of this 5% about 3% results from the
      difference in the uncorrected scatter contribution. In conclusion, an in-FOV
      shield can be used successfully in an HRRT PET scanner to improve NECR and
      accuracy of small animal brain studies. The latter is especially important when
      high activities are required for tracers with low brain uptake or when multiple
      animals are scanned simultaneously.

PMID- 14703173
TI  - Call for more veterinary training in organic systems.

PMID- 14703174
TI  - Disgraceful conduct case dismissed.

PMID- 14703175
TI  - Profession must 'be prepared' for a new Veterinary Surgeons Act.

PMID- 14703177
TI  - Measurements of the degree of development of rigor mortis as an indicator of
      stress in slaughtered pigs.
AB  - The degree of development of rigor mortis in the carcases of slaughter pigs was
      assessed subjectively on a three-point scale 35 minutes after they were
      exsanguinated, and related to the levels of cortisol, lactate and creatine kinase
      in blood collected at exsanguination. Earlier rigor development was associated
      with higher concentrations of these stress indicators in the blood. This
      relationship suggests that the mean rigor score, and the frequency distribution
      of carcases that had or had not entered rigor, could be used as an index of the
      degree of stress to which the pigs had been subjected.

PMID- 14703178
TI  - Pulsed-wave Doppler echocardiography in birds of prey.
AB  - Pulsed-wave spectral Doppler echocardiography was applied to 111 diurnal and
      nocturnal raptors of both sexes weighing between 190 and 4200 g. In the first
      stage, 40 birds were examined without special preparation; in the second stage,
      15 birds were examined first when they were not anaesthetised and then when they
      were anaesthetised; in the third stage, 41 birds were examined after they had
      been fasted for different periods of time; and finally 15 birds, in which
      echocardiography had not been possible by using standard (dorsal) restraint and
      positioning, were examined after being placed in lateral and ventral recumbency.
      Doppler-derived diastolic inflow into the ventricles was detectable in
      approximately 80 per cent of the birds weighing between 190 and 2300 g
      independently of their weight, heart rate and whether they had been anaesthetised
      or fasted, and aortic blood flow was detected in about 50 per cent of them. It
      was possible to apply the technique under standard conditions of dorsal
      recumbency to only one of the birds weighing more than 3000 g and to about 80 per
      cent of those weighing between 190 and 2300 g. In 11 of 15 birds in which the
      technique could not be applied under standard conditions, blood flow could be
      detected in the ventricles and/or the aorta after the birds had been
      repositioned. No systolic blood flow through the pulmonary artery was detectable
      in any of the birds.

PMID- 14703179
TI  - Experimental Corynebacterium pseudotuberculosis mastitis in dairy cows.
AB  - The inoculation of 2000 colony-forming units of Corynebacterium
      pseudotuberculosis into one teat canal of each of three cows resulted in severe,
      chronic, pyogranulomatous mastitis. Within three days the cows had a reduced
      haematocrit, haemoglobin concentration and red cell count. The anaemia was
      initially normocytic, normochromic and non-regenerative, and was associated with
      a brief peak of neutrophilia; a regenerative response became evident two to three
      weeks later. Clinical signs of mastitis appeared seven to 14 days after the
      inoculation, with a peak of high fever, more severe anaemia, a second peak of
      neutrophilia and the complete cessation of milk production from all quarters;
      extensive and severe pyogranulomatous mastitis developed in the inoculated
      quarters. No other lesions were detected postmortem, and C pseudotuberculosis was
      cultured from the affected quarters but not from the supramammary lymph nodes and
      viscera.

PMID- 14703180
TI  - Antigenic type distribution of parvovirus isolated from domestic cats in Japan.

PMID- 14703181
TI  - Investigation and management of necrotising orchitis associated with a scrotal
      haematoma in a Texel ram.

PMID- 14703182
TI  - Polycystic kidney disease in an aged pony.

PMID- 14703183
TI  - Laboratory animal medicine.

PMID- 14703184
TI  - Laboratory animal medicine.

PMID- 14703185
TI  - Laboratory animal medicine.

PMID- 14703186
TI  - Continuing anxiety about BSE.

PMID- 14703187
TI  - Gangrenous mastitis in dairy herds.

PMID- 14703188
TI  - Veterinary surveillance.

PMID- 14703189
TI  - FMD control strategies.

PMID- 14703190
TI  - Cryopreservation of Giardia lamblia.

PMID- 14703191
TI  - Prevention of S enteritidis on commercial laying chicken farms.

PMID- 14703192
TI  - Is medical professionalism still relevant?

PMID- 14703193
TI  - Basic mechanisms and clinical implications of peritoneal fibrosis.
AB  - We have stressed the role of certain growth factors and cytokines in peritoneal
      fibrosis, including TGFbeta, TIMP-1, and inflammatory cytokines, especially IL
      1beta. Recent research highlights the myofibroblast-like transformation of
      mesothelial cells as a central initiating event in peritoneal fibrosis. The
      induction, survival, and apoptosis of the myofibroblast cell population likely
      dictate the nature of the fibrogenic response. The accumulation of collagen
      occurs in a nondegradative environment, and collagenases and their inhibitors
      have a role in the maintenance of fibrosis. Fibrosis appears to be a ubiquitous
      response of peritoneal tissues to the damaging effects of uremia, bioincompatible
      dialysate, recurrent infection, and inflammation. Recent research has focused on
      the induction of angiogenesis, as this appears to correlate with increased solute
      transport and peritoneal membrane ultrafiltration failure. Fibrosis may play an
      integral part in peritoneal membrane dysfunction in several aspects. Angiogenesis
      may be induced as part of the fibrotic response, as many key fibrogenic cytokines
      are also strongly angiogenic. Fibrotic tissue may support and preserve
      angiogenesis. Changes in the interstitium may have a direct effect on the
      hydrodynamic properties of the peritoneum and may directly influence fluid
      movement. In its most extreme form, fibrosis manifests as the rare but
      devastating EPS. Peritoneal biopsy studies have identified a high prevalence of
      peritoneal fibrosis in PD patients. Research into peritoneal fibrosis will be
      enhanced by new animal models where the role of various cytokines and growth
      factors, cellular processes, and matrix interactions can be studied. With these
      models, the role of fibrosis in alteration of peritoneal membrane function can be
      better assessed. Clinical trials to assess the role of prevention of peritoneal
      injury using biocompatible solutions and treatments targeted directly at
      peritoneal fibrosis will be important, but challenging to design and carry out.

PMID- 14703194
TI  - Is the peritoneum a significant transport barrier in peritoneal dialysis?
AB  - OBJECTIVES: The anatomic peritoneum is often considered equivalent to the barrier
      between the dialysate and the blood, and is also called "the peritoneal
      membrane." Our hypothesis is that the normal peritoneum is not a significant
      barrier to solute or water flow. The goal of this study was to explore the
      effects of alteration of the anatomic peritoneum on the transperitoneal transport
      of water and solute. DESIGN: In vivo transport experiments were carried out in
      control and treated rats. Treatments consisted of frequent mixing of the
      peritoneal solution versus no mixing, drying the peritoneum prior to the
      experiment, or selective removal of the entire peritoneum. Transport experiments
      were carried out via a plastic chamber affixed to the parietal peritoneum. After
      measuring solute transport or osmotically induced filtration, the tissue
      underlying the chamber was collected and stained for histology. RESULTS: Mixing
      the chamber solution every 5 minutes versus no mixing over 90 minutes did not
      result in a significant change in the mass transfer coefficient for mannitol
      (MTCmannitol, n = 14, p > 0.25). Drying the peritoneum prior to the transport
      experiment did not significantly alter the MTC of albumin or mannitol (n = 17, p
      > 0.6; n = 19, p > 0.1, respectively). Manual drying did not remove or
      significantly alter the apparent peritoneal coating on the surface of the
      mesothelium. Removal of the entire peritoneum did not significantly alter the
      osmotically induced volume flux from the tissue, nor did it change the
      MTCmannitol (n = 9, p > 0.9; n = 9, p > 0.4, respectively). CONCLUSIONS: Mixing
      of the solution directly over the tissue, manual drying of the peritoneum, or
      removal of the entire peritoneum does not result in significant alterations in
      transport. We conclude that the anatomic peritoneum is relatively unimportant as
      a physical transport barrier in peritoneal dialysis.

PMID- 14703195
TI  - Disturbed appetite patterns and nutrient intake in peritoneal dialysis patients.
AB  - OBJECTIVE: Malnutrition is common among peritoneal dialysis (PD) patients.
      Reduced nutrient intake contributes to this. It has long been assumed that this
      reflects disturbed appetite. We set out to define the appetite profiles of a
      group of PD patients using a novel technique. DESIGN: Prospective, cross
      sectional comparison of PD patients versus controls. SETTING: Teaching hospital
      dialysis unit. PATIENTS: 39 PD patients and 42 healthy controls. INTERVENTION:
      Visual analog ratings were recorded at hourly intervals to generate daily
      profiles for hunger and fullness. Summary statistics were generated to compare
      the groups. Food intake was measured using 3-day dietary records. MAIN OUTCOME
      MEASURES: Hunger and fullness profiles. Derived hunger and fullness scores.
      RESULTS: Controls demonstrated peaks of hunger before mealtimes, with fullness
      scores peaking after meals. The PD profiles had much reduced premeal hunger
      peaks. A postmeal reduction in hunger was evident, but the rest of the trace was
      flat. The PD fullness profile was also flatter than in the controls. Mean scores
      were similar despite the marked discrepancy in the profiles. The PD group had
      lower peak hunger and less diurnal variability in their hunger scores. They also
      demonstrated much less change in fullness rating around mealtimes, while the mean
      and peak fullness scores were little different. The reported nutrient intake was
      significantly lower for PD. CONCLUSION: The data suggest that PD patients
      normalize their mean appetite perception at a lower level of nutrient intake than
      controls, suggesting that patient-reported appetite may be misleading in clinical
      practice. There is a loss of the usual daily variation for the PD group, which
      may contribute to their reduced food intake. The technique described here could
      be used to assess the impact of interventions upon the abnormal PD appetite
      profile.

PMID- 14703196
TI  - Evaluation of nutritional status and factors related to malnutrition in children
      on CAPD.
AB  - OBJECTIVE: The aim of this study was to investigate the nutritional status of
      children on continuous ambulatory peritoneal dialysis (CAPD) and to relate it to
      the dose of dialysis and serum levels of inflammatory cytokines and insulin-like
      growth factor-1 (IGF-1). PATIENTS: 17 CAPD patients (8 girls, 9 boys; mean age
      13.1 +/- 3.5 years, median 15 years) were included in the study. Anthropometric
      measurements and serum albumin levels were used in the evaluation of nutritional
      status. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha, and IGF
      1 levels were determined in all CAPD patients and in a healthy control group.
      Weekly Kt/V and creatinine clearance (CCr) were measured to determine adequacy of
      dialysis. RESULTS: The mean dialysis period was 23.7 +/- 15.2 months (median 23
      months). Anthropometric measurements and serum albumin level were as follows:
      height 130.2 +/- 15.6 cm, height standard deviation score (HtSDS) -4.2 +/- 2.4,
      body mass index (BMI) 16.3 +/- 1.6 kg/m2, body mass index standard deviation
      score (BMISDS) -0.8 +/- 0.9, triceps skinfold thickness (TST) 4.2 +/- 1.4 mm,
      midarm circumference (MAC) 16.21 +/- 2.3 cm, upper arm muscle area (AMA) 1799.1
      +/- 535.7 mm2, upper arm fat area (AFA) 334.5 +/- 143 mm2, and serum albumin 3.1
      +/- 0.7 g/dL. The BMI was above the fifth percentile in all patients; TST and MAC
      were below the fifth percentile in 14 patients (82.4%) and 10 patients (58.8%)
      respectively. The AMA was below the fifth percentile in 8 patients; however, the
      AFA was below the fifth percentile in all patients. Mean serum albumin level was
      under 3.5 g/dL in 70.5% of the children. We found significant positive
      correlations between BMI and Kt/V (r = 0.69, p < 0.01), CCr (r = 0.64, p < 0.05),
      and IL-6 (r = 0.61, p < 0.01). There was an inverse correlation between BMISDS
      and dialysis period (r = -0.58, p < 0.05); and between IL-6 and serum albumin (r
      = -0.49, p < 0.05). A significant positive correlation between BMISDS and serum
      IGF-1 level (r = 0.62, p < 0.01) was noted. We also found a significant positive
      correlation between serum IGF-1 level and both HtSDS (r = 0.57, p < 0.05) and TST
      (r = 0.52, p < 0.05). Significant positive correlations between AFA and CCr and
      IGF-1 were also noted (both r = 0.56, p < 0.05). CONCLUSION: Although many
      factors may be responsible for malnutrition and growth retardation, we found that
      prolonged period of dialysis, inadequate dialysis, and low IGF-1 levels are the
      most important risk factors in CAPD patients.

PMID- 14703197
TI  - Blood pressure control and left ventricular hypertrophy in long-term CAPD and
      hemodialysis patients: a cross-sectional study.
AB  - BACKGROUND: It is still not clear whether hypertension and left ventricular
      hypertrophy (LVH) are more common in continuous ambulatory peritoneal dialysis
      (CAPD) than in hemodialysis (HD) patients. METHODS: To examine this subject, the
      indices of cardiac performance were compared between 50 HD and 34 CAPD patients.
      Patients were further divided into two subgroups [long-term (L) CAPD and L-HD]
      according to dialysis modality and duration of dialysis (more than 60 months'
      duration). RESULTS: The blood pressure and cardiothoracic index of CAPD patients
      did not differ from HD patients. On average, the left atrial index was 2 mm/m2
      higher in HD patients than in CAPD patients. Left ventricular chamber sizes, wall
      thickness, and left ventricular mass index (LVMI) in patients on CAPD were
      similar to those of HD patients. Isovolumic relaxation time (IVRT) of CAPD
      patients was insignificantly less than that of HD patients (101 +/- 22 and 115 +/
      27 msec respectively). There was no significant difference between the two
      subgroups (L-HD and L-CAPD) in blood pressure, left atrial diameter, left
      ventricular chamber size, wall thickness, LVMI, ejection fraction, or IVRT.
      CONCLUSION: If normovolemia and normotension are obtained by strict volume
      control without using antihypertensive drugs, the effects of the two modalities
      of chronic dialysis treatment (HD and CAPD) on cardiac structure and function are
      not different from each other.

PMID- 14703198
TI  - Comparison of the Charlson Comorbidity Index and the Davies score as a predictor
      of outcomes in PD patients.
AB  - BACKGROUND: Comorbidity is a strong predictor and confounds many studies of
      outcomes. Previous studies have shown that the Charlson Comorbidity Index (CCI)
      and the Davies score predict mortality in peritoneal dialysis (PD) patients.
      However, there are few data on the comparison of comorbidity scores. OBJECTIVE:
      To compare the CCI (combines comorbidity and age) and Davies score (comorbidity
      score without age) to see if one score was superior to the other in predicting
      outcomes. DESIGN: Prospective database study. SETTING: Seven dialysis centers in
      Western Pennsylvania. PARTICIPANTS: 415 incident PD patients, starting PD from
      1/1/90 to 2/1/00. MEASUREMENTS: The CCI and Davies score calculated at the start
      of PD; serum albumin levels and demographics at the start of PD; total
      hospitalizations and mortality, collected prospectively. RESULTS: The correlation
      between CCI and Davies was 0.80, p < 0.0001. The CCI was inversely correlated
      with serum albumin (-0.31, p < 0.0001). Davies was significantly correlated with
      age (0.32, p < 0.0001) and inversely correlated with albumin (-0.27, p < 0.0001).
      The CCI alone was a stronger predictor than Davies alone (score by best subsets
      regression 49.6 vs 42.0, p = 0.0058). The CCI and Davies with age appeared to be
      equivalent models of survival (49.61 vs 49.64). The best predictive models were
      CCI and initial albumin, or Davies, age, and initial albumin. Both CCI and Davies
      were predictors of hospitalization rates, but the model with the Davies score was
      better (Akaike information criterion 799.2 vs 850.2). The best predictive model
      was Davies, albumin, age, and race. CONCLUSIONS: Both comorbidity scores were
      significant predictors of outcomes, with CCI the stronger predictor for
      mortality, but the Davies was a stronger predictor of hospitalizations. One or
      both should be done at the start of dialysis to predict outcome.

PMID- 14703199
TI  - Pharmacokinetics of ceftazidime in CAPD-related peritonitis.
AB  - OBJECTIVE: The aim of this study was to measure and evaluate the appropriateness
      of the actual concentrations of serum and dialysate ceftazidime in Thai
      continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective
      and descriptive study of patients treated following the International Society for
      Peritoneal Dialysis (ISPD) 2000 recommendation for the empiric therapy of CAPD
      related peritonitis. SETTING: Institutional level of clinical care. PATIENTS:
      CAPD-related peritonitis patients were diagnosed by dialysate effluent white
      blood cell count of more than 100/mm3 and polymorphonuclear leukocytes of at
      least 50%. There were 10 patients, all at least 18 years of age, entered; all
      completed the study. INTERVENTION: In accordance with the ISPD 2000
      recommendations, the antibiotic regimen comprised continuous intraperitoneal
      (i.p.) cefazolin and once-daily i.p. ceftazidime. Cefazolin was administered as
      loading and continuous maintenance doses of 500 and 125 mg/L dialysate
      respectively. Ceftazidime (20 mg/kg body weight) was given i.p. once daily.
      Duration of treatment was 96 hours. MAIN OUTCOME MEASURES: Serum and dialysate
      effluent samples of the 10 CAPD patients with peritonitis were measured for
      ceftazidime levels, which were used for the development of pharmacokinetic
      equations that could predict drug concentrations at any treatment time. RESULTS:
      Following ceftazidime administration as in the ISPD 2000 recommendation, serum
      ceftazidime levels were above 8 microg/mL, the minimum inhibitory concentration
      (MIC) recommended by NCCLS, throughout 24 hours. Dialysate ceftazidime levels
      were below the MIC for total periods of 4.19 and 6.26 hours in day 1 and day 4
      respectively. The clinical response rate to the empiric regimen was 90%.
      CONCLUSIONS: Once-daily i.p. administration of ceftazidime according to the ISPD
      2000 recommendation could not provide adequately therapeutic levels of
      ceftazidime in dialysate throughout 24 hours. Despite this finding and the poor
      post-antibiotic property of ceftazidime, the empiric regimen including once-daily
      i.p. ceftazidime could yield good clinical outcome.

PMID- 14703200
TI  - Influence of climate on the incidence of peritoneal dialysis-related peritonitis.
AB  - OBJECTIVE: The use of peritoneal dialysis has expanded in many developing
      subtropical countries; however, the role of climatic factors in dialysis-related
      peritonitis has not been studied in detail. DESIGN: Retrospective study. SETTING:
      A single regional dialysis unit in a university teaching hospital. PATIENTS: We
      reviewed all cases of dialysis-related peritonitis treated in our dialysis unit
      from January 1995 to December 2001. Information was collected on demographic
      data, microbiologic etiology, associated catheter exit-site infection, and
      clinical response. RESULTS: In 24,059 patient-months of follow-up, 1344 episodes
      of peritonitis were recorded. There were significantly more peritonitis episodes
      in July and August [odds ratio 1.17, 95% confidence interval (CI) 1.03-1.32], and
      fewer peritonitis episodes in December (odds ratio 0.79, 95% CI 0.61-0.98). There
      was also a trend of more peritonitis in March (odds ratio 1.18, 95% CI 0.97
      1.41), but the difference was not statistically significant. When the incidence
      of peritonitis caused by individual bacterial species was further analyzed, we
      found a significant seasonal variation in the rate of peritonitis caused by gram
      negative bacteria, except Pseudomonas (overall chi-square test, p = 0.002). A
      similar trend of seasonal variation was also observed in gram-positive
      peritonitis, but the result was not statistically significant. There was
      significant seasonal variation in the rate of peritonitis that had coexisting
      exit-site infection (overall chi-square test, p = 0.02), with peak incidence in
      July. However, the proportion of peritonitis that had coexisting exit-site
      infection did not have significant seasonal variation. There was significant
      correlation between monthly peritonitis rate and average humidity (r = -0.346, p
      < 0.002) and temperature (r = -0.264, p = 0.015). CONCLUSIONS: There is
      substantial seasonal variation in the incidence of dialysis-related peritonitis,
      with peak incidence in the months that are hot and humid. Keeping a cool and dry
      living environment may help to reduce peritonitis in peritoneal dialysis patients
      in tropical countries.

PMID- 14703201
TI  - Double guidewire method: a novel technique for correction of migrated Tenckhoff
      peritoneal dialysis catheter.
AB  - Twenty-two consecutive patients with a continuous ambulatory peritoneal dialysis
      (CAPD) catheter malfunctioning due to catheter migration were treated with a
      novel radiological manipulation technique, the "double guidewire method." The
      first guidewire is used to correct the direction of the catheter tip and the
      second wire is used to anchor the CAPD catheter so that an ideal course of the
      catheter can be maintained during removal of the first guidewire. Immediate
      catheter repositioning was achieved in 19 of 22 patients, and durable
      repositioning success was achieved in 13 patients. In conclusion, the "double
      guidewire method" is a simple but effective technique for prolonging CAPD
      catheter life in patients with malfunction due to catheter migration.

PMID- 14703202
TI  - Bioimpedance analysis and assessment of intracellular water in peritoneal
      dialysis patients.

PMID- 14703203
TI  - Comparative study of mupirocin and sodium fucidate in the prophylaxis of exit
      site infections in CAPD patients.

PMID- 14703204
TI  - Effect of oral treatment with the glycosaminoglycan sulodexide on peritoneal
      transport in CAPD patients.

PMID- 14703205
TI  - Treatment of gram-positive peritonitis in peritoneal dialysis patients: cefazolin
      or vancomycin?

PMID- 14703206
TI  - Computed tomography-based assessment of bone mineral density in patients treated
      with peritoneal dialysis.

PMID- 14703207
TI  - Intraperitoneal infusion allows therapeutic plasma levels of cefepime.

PMID- 14703208
TI  - What should plasma bicarbonate levels be in peritoneal dialysis patients?

PMID- 14703209
TI  - Total fluid removal and small solute clearances.

PMID- 14703210
TI  - Delayed colonic perforation caused by an unused CAPD catheter in a patient
      presenting with diarrhea.

PMID- 14703211
TI  - Moraxella and Kluyvera peritonitis in a CAPD patient with human immunodeficiency
      virus.

PMID- 14703212
TI  - Blood blood everywhere !!

PMID- 14703213
TI  - Comparison of shear bond strength of composite, compomer and resin modified glass
      ionomer in primary and permanent teeth: an in vitro study.
AB  - The aim of this study was to determine the difference in shear bond strength
      between Composite, Compomer and Resin modified glass ionomer cement in primary
      and permanent teeth. Thirty extracted primary molars and thirty premolars were
      selected and buccal surfaces of all the teeth were made smooth with the help of
      300 grit silicon carbide paper. These specimens were then divided into 6 groups.
      Restorative materials were placed on the buccal surfaces of respective specimens
      with the help of acrylic template. All the specimens were subjected to
      thermocycling and shear bond strength was tested under the Honsfield testing
      machine and results were recorded in megapascals (MPa). The resultant scores were
      tabulated and statistically analysed. It was observed that in case of primary
      teeth resin modified glass ionomer exhibited significantly higher shear bond
      strength as compared to composite and compomer, where as on permanent teeth
      composite demonstrated a significantly higher shear bond strength than that of
      the resin modified glass ionomer and compomer, where as compomer gave poor shear
      bond strength in both primary and permanent teeth.

PMID- 14703214
TI  - Biologic restoration of primary anterior teeth: a case report.
AB  - Restoration of primary maxillary incisors, severely destroyed by trauma or caries
      is a commonly faced problem in a Pediatric dental clinic. Most cases are observed
      in children with early childhood caries. In the past, the only option would have
      been to extract the affected teeth and replace them with prosthetic substitutes.
      However, the availability of natural crowns and roots would allow the use of
      biologic restorations to preserve the integrity of patient's natural dentition as
      presented in this case report.

PMID- 14703215
TI  - Comparative evaluation of efficacy of sodium fluoride, chlorhexidine and
      triclosan mouth rinses in reducing the mutans streptococci count in saliva : an
      in vivo study.
AB  - The primary objective of this study was to compare the efficacy of sodium
      fluoride (0.05%), chlorhexidine (0.12%) and triclosan (0.3%) mouth rinses in
      reducing the mutans streptococci count in saliva. 60 subjects in the age group of
      12 to 14 years were selected from the schools of Mumbai and were equally divided
      into 4 groups. First 3 groups were test groups and the 4th group was control
      group. The subjects were instructed to rinse one full marked measure of mouth
      rinse for 1 minute, twice daily. Salivary samples were collected at baseline and
      after 2 weeks and cultured on M.S.B.agar. The number of mutans streptococci
      colonies were counted on agar medium. The results of the study confirmed that
      chlorhexidine mouth rinses are more efficient in reducing mutans streptococci
      count in saliva as compared to other mouth rinses.

PMID- 14703216
TI  - Eosinophilic granuloma with oral manifestations: a case report.
AB  - Eosinophilic granuloma is the most benign disorder of the triad commonly known as
      histocytosis X. In this article a case of a 6 year old female child with multiple
      eosinophilic granuloma with additional liver dysfunction and its oral
      manifestation is presented. This case demonstrated that oral findings, may be an
      early manifestation of the disease, definitive diagnosis needs to be determined
      by correlation of the clinical findings with histologic features. For the
      duration of 8 years the case has been followed up, there has been a progressive
      healing of the lesion, the clinical manifestations of the disease resolved with
      only chemotherapy and provided a very good prognosis.

PMID- 14703217
TI  - Microbial contamination of tooth brushes and their decontamination.
AB  - With the dawn of the new century, dentistry has seen a new face in the fields of
      diagnosis, treatment and prevention. Twenty one children were asked to brush
      their teeth for five days. The brushes were put in Robertson's Cooked Meat broth
      and cultured. Growth of Streptococcus Mutans were seen. These brushes were then
      placed in disinfectants such as 0.2% chlorhexidine gluconate (Gp I), 1% sodium
      hypochlorite(Gp II) and water (Gp III) for 24 hrs and then cultured.
      Disappearance of growth of microorganisms was seen in Gp I and Gp II and remnants
      of growth seen in Gp III. It can be concluded that the use of disinfectant is a
      must for every individual at regular intervals.

PMID- 14703218
TI  - Canine ectopia: report of two cases.
AB  - Transmigration of mandibular canine is a rare elusive phenomenon described in
      dental literature. The eruption of such transmigrated canines is even rarer. Two
      rare cases one of midline mandibular canine and the other of transmigrated
      mandibular canine across the midline and erupted distal to the opposite lateral
      incisor are presented. The transmigrated canine maintained its nerve supply from
      the original site. It is suggested that on routine evaluation of
      orthopantomograms when the dentist finds an excessive mesial inclination of the
      unerupted mandibular canine at 8-9 years associated with proclination of lower
      anteriors. increased axial inclination of the unerupted canine and an enlarged
      symphyseal cross section area of the chin, it is best to keep such a patient
      under routine evaluation.

PMID- 14703219
TI  - Tooth fragment reattachment--an esthetic alternative: report of a case.
AB  - Trauma to the anterior teeth is relatively common among children and teenagers.
      Reattachment of a fractured fragment to the remaining tooth can provide better
      and long lasting esthetics, improved function, a positive psychological response
      and is a faster and less complicated procedure. This article discusses fragment
      reattachment technique and presents clinical case of coronal fracture involving
      enamel and dentin.

PMID- 14703220
TI  - Oral habits in school going children of Delhi: a prevalence study.
AB  - This study was conducted on 5554 children aged 5-13 years old with the objectives
      of recording the prevalence of oral habits among North Indian children according
      to sex. These children were selected from the schools of Delhi. The sample
      represented the entire school-going population of Delhi in the age group of 5-13
      years. Statistical analysis was carried out using BMDP software and sex
      differences were calculated by using Fisher's exact test. The results showed that
      the prevalence of oral habits in Delhi school going children was 25.5%. Tongue
      thrust was the commonest habit (18.1%) followed by mouth breathing (6.6%). Thumb
      sucking was relatively less common habit and seen in only 0.7% of children. There
      were no significant differences between boys and girls for the prevalence of oral
      habits. However, for the specific habit types there was a sex difference. Thumb
      sucking was more common in girls (1.0%) when compared with boys (0.4%) and this
      difference was statistically significant (P < 0.001). There was a reverse trend
      for the mouth breathing, which was more common (P < 0.001) in boys (7.8%) than
      girls (5.3%). There were no differences for tongue thrust habit between boys
      (17.5%) and girls (18.6%).

PMID- 14703221
TI  - Glucose-6-phosphate dehydrogenase deficiency in neonates.
AB  - OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited
      deficiency that may be the cause of neonatal hyperbilirubinemia, as has been
      found in several countries and among widely different ethnic groups, especially
      in Mediterranean region. Our aim was to study the prevalence of G6PD deficiency
      in relation to neonatal jaundice. METHODS: From March 1998 to April 2001 we
      studied 705 clinically icteric neonates who were admitted to Al-Zahra and
      Beheshti hospitals, two teaching hospitals in Isfahan, Iran. Laboratory
      investigations included determination of direct and indirect serum bilirubin
      concentrations, blood group typing, direct coomb's test, hemoglobin, blood smear,
      reticulocyte count and G6PD level. RESULTS: In only 53 (7.5%) of cases G6PD
      deficiency was diagnosed. In all G6PD deficient neonates no evidence of other
      factors known to cause hyperbilirubinemia were detected. The sex distribution was
      13 (24.5%) females and 40 (75.5%) males in the G6PD deficient group. The mean
      bilirubin level in G6PD deficient and G6PD normal groups were 22.26 +/- 8.36 and
      18.14 +/- 3.85 mg/dl, respectively (p=0.001). Phototherapy was required in G6PD
      deficient and other icteric neonates with duration of 3.76 +/- 1.93 and 3.13 +/-
      2.14 days, respectively (p=0.045). Twenty-seven of the 53 (50.9%) G6PD deficient
      infants required exchange transfusion. None of them developed kernicterus.
      CONCLUSIONS: Since the prevalence of severe hyperbilirubinemia among our neonates
      was relatively high and about half of them required exchange transfusion, early
      detection of this enzymopathy regardless of sex and close surveillance of the
      affected newborns may be important in reducing the risk of severe
      hyperbilirubinemia and exchange transfusion.

PMID- 14703222
TI  - Ascites in ventriculoperitoneal shunt.
AB  - OBJECTIVE: To fetch out the factors responsible for ascites, following shunt CSF
      diversion in cases of intracarnial lesions. Four children developing
      ascites/abdominal psuedocyst following ventriculoperitoneal shunt were analyzed
      to see the factors responsible for such complication. METHODS: Records of 4 cases
      developing ascites were studied retrospectively. These children developed ascites
      at 8 months, 6 months, 1 year and 1 year 2 months interval following their shunt
      installation. RESULTS: The primary etiology of hydrocephalus was demonstrated as
      thalamic glioblastoma, choroid plexus papillomas of third ventricle, post
      tubercular meningitis hydrocephalus and suprasellar craniopharyngioma.
      CONCLUSION: The proposed etiology of ascites in these cases was peritoneal
      metastasis from thalamic glioblastoma through ventriculoperitoneal shunt in first
      case, excessive production of CSF by choroid plexus papilloma in second,
      infection in the third case and craniopharyngioma causing excessive production of
      CSF in the fourth child. All the children were treated by reasonable laparotomy
      and fenestration of cyst along with the repositioning of shunt tip at another
      site.

PMID- 14703223
TI  - Clinical profile and outcome of acute respiratory failure.
AB  - OBJECTIVE: To examine the etiological factors, clinical features, treatment
      modalities and outcome of acute respiratory failure in children. METHODS: This
      hospital-based prospective observational study was conducted over 15 months.
      Fifty children with acute respiratory failure, diagnosed by serial arterial blood
      gas analysis, were consecutively enrolled. Ventilation therapy was initiated when
      the FiO2 requirement went above 0.6. RESULTS: Pulmonary diseases accounted for
      majority (68%) of cases, followed by nervous system (12%); and cardiovascular and
      skeletal muscle system diseases (10%, each). Bronchopneumonia was the commonest
      cause of acute respiratory failure (11 cases). The majority of cases were in the
      age group 1 month to < 1 year (26 cases). The commonest signs were altered depth
      and pattern of respiration (100%), chest wall retractions (88%), flaring of alae
      nasae (88%), tachypnea (84%), tachycardia (82%), and irritability (64%). Cyanosis
      was noticed in only 26 (52%) cases. Thirty-six (72%) children required
      ventilation therapy. The overall mortality was 58%. The mortality was high (55.9%
      to 66.7%), irrespective of the primary system involved. Significantly higher
      mortality was associated with co-existent malnutrition (p<0.001), Type I failure
      (p=0.039) and ventilation therapy (p<0.0001). CONCLUSION: Acute respiratory
      failure has varied etiology and clinical manifestations, and a high mortality.
      Its outcome is independent of age of the child and the primary system involved.
      Malnutrition and Type I failure are factors associated with a poor outcome.

PMID- 14703224
TI  - Reliability of perception of fever by touch.
AB  - OBJECTIVE: To assess the reliability of touch to predict fever in children.
      METHODS: 200 children who reported with fever formed the study material. Group I
      consisted of 100 children between 0-1 year of age and Group II consisted of 100
      children between 6-12 years of age. Preterm, neonates under warming device,
      tachypnoeic and hypothermic were excluded from the study. The caregiver (CG) and
      the medical staffs (MS) response regarding presence or absence of fever by touch
      was noted in each child. Both were blinded to each other's response. Immediately
      temperature was recorded by calibrated rectal thermometer in Group I and
      calibrated axillary thermometer in Group II. RESULTS: The CG's touch had a
      sensitivity of 70.5% specificity of 40.9%, PPV of 38% NPV of 72.9%, PLR was 1.16
      and NLR was 0.75. The MS's touch had a sensitivity of 78.0%, specificity of
      63.6%, PPV of 38.0% NPV 84.8%, PLR of 2.08 and NLR of 0.36. There is over and
      under diagnosis of fever by both, the former being more by the CG reflecting the
      parental anxiety. The MS's touch is better to affirm or negative fever as
      compared to CG. The best site to palpate for presence of fever was abdomen, neck
      and forehead. CONCLUSION: Touch is not a valid screening test for fever. It is
      recommended that a thermometer must always be used by the MS to record fever and
      CG must be motivated for the same.

PMID- 14703225
TI  - Choanal atresia: transnasal endoscopic technique.
AB  - OBJECTIVE: This article attempts to address the controversy between, endoscopic
      and traditional approaches to neonatal choanal atresia. METHOD: Congenital
      choanal atresia has been recognized for over 200 years, first described by
      Roedere in 1775. This condition is uncommon, occurring in approximately 1 in 7000
      live births. Unfortunately a single ideal procedure for this condition does not
      exist. RESULTS: Stankiewicz is credited with the first description of endoscopic
      techniques for choanal atresia repair. All patients diagnosed to have choanal
      atresia, treated between 1999 and 2000 were reviewed. Out of four patients two
      underwent endoscopic repair. CONCLUSION: Transnasal endoscopic technique is
      followed by stenting with endotracheal portex tubes for 4-6 weeks in the initial
      surgical procedure of choice.

PMID- 14703226
TI  - Disposable diapers: a hygienic alternative.
AB  - The use of disposable diapers has offered improved health care benefits. Urine
      and fecal matter leakage from the cloth nappies and the hand-to-mouth behavior in
      infants leads to many illnesses with a feco-oral mode of transmission. Also, the
      tender skin of the infant is more prone to nappy rash. The modern age disposable
      diapers, when compared to cloth nappy, have displayed a superior ability in
      containment of urine and feces, thereby reducing contamination and transmission
      of infection. Also disposable diapers contain Super Absorbent Material (SAM) that
      successfully reduces the incidence of nappy rash.

PMID- 14703227
TI  - Attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most commonly
      diagnosed behavior disorder of childhood. In recent years, increasing number of
      preschoolers appear to be manifesting the core symptoms of ADHD. Diagnosis of
      ADHD in very young children is difficult as high activity level, impulsivity and
      short attention span are to some extent age appropriate characteristics of normal
      pre-school children. Concerns both about over-diagnosis and under-diagnosis have
      been expressed in the literature. Management emphasizing parental counseling,
      behavior management strategies, and appropriate pharmacotherapy is recommended.

PMID- 14703228
TI  - Directly observed treatment for tuberculosis.
AB  - Directly Observed Treatment-Short Course (DOTS) has been a successful strategy in
      the global control of tuberculosis (TB) in adults. However, reports of
      implementation are scantily available in pediatric context. Present article
      reviews diagnostic uncertainties of TB in children commonly faced by physicians
      on account of the vague clinical presentations, unreliable tuberculin tests or TB
      score charts, non-specific hematological, biochemical or radiological evidence,
      difficulty in sputum expectoration and non-availability or ill-affordability of
      specialised tests. It also describes therapeutic problems arising due to the
      physician's inexpertise, child's incomprehensibility and parental anxiety. DOTS
      was found to be highly effective in 930 Indian children having TB over the 6-year
      study period, during which, a rise in number of cases with adult pattern of
      disease was also noted. The trend change in pediatric TB scenario is thought to
      have taken place due to malnutrition so widely prevalent in this country.
      Irrespective of the changing trend, DOTS strategy was found to be effective for
      all types of pediatric TB. A need, therefore, exists for quick resolution of the
      programme issues related to pediatric drug dispensing, physicians' reservations
      about acceptance of strategy in this age-group, service-utilisation of DOTS
      providers for the selected cases unable to visit DOTS centres and giving
      executional priority to children during ongoing expansion of Revised National TB
      Control Programme (RNTCP) in country.

PMID- 14703229
TI  - Perspectives in hematology.

PMID- 14703230
TI  - Anemia in the newborn.
AB  - In neonatal period anemia is a complex problem owing to the unique blood picture.
      The erythrocytic system undergoes serial adaptation to meet progressively
      changing demands of oxygen in the embryo, the fetus and neonate. This leads to
      rapid change in normal hematological change in post-birth period. Definition of
      anemia is difficult because as described earlier, several important factors
      influence normal blood in the newborn infants. The etiology of neonatal anemia
      can be classified into i) hemorrhage (ii) hemolysis (iii) failure of red cell
      production. Severe fetal hemorrhage may accompany various placental anomalies
      like placenta praevia, abruptio placenta and accidental incision of placenta
      during the caesarian section. It is reported that 10% of all infants born
      following placenta praevia and 4% of infants born following abruptio placenta
      present with severe anemia. The passage of fetal erythrocytes in maternal
      circulation occurs commonly during pregnancy. In 50% of pregnancies some fetal
      cells are passed in maternal circulation sometimes during gestation or during
      birth process. Treatment of a neonate with anemia due to blood depends on the
      degree of hypovolemia or anemia and whether the blood loss has been acute or
      chronic. Newborn with pale skin should be differentiated from an asphyxiated
      baby.

PMID- 14703231
TI  - Neonatal thrombosis.
AB  - Neonatal thrombosis is a serious event that can cause mortality or result in
      severe morbidity and disability. The most important risk factor for the
      development of thrombosis during the neonatal period is the presence of an
      indwelling central line and consequently the vessels involved tend to be those
      most frequently used for catheterization. Other documented risk factors for the
      development of neonatal thrombosis include asphyxia, septicemia, dehydration,
      maternal diabetes and cardiac disease. Main laboratory findings for the diagnosis
      of hypercoagulable states, include shortened aPTT, decreased levels of inhibitors
      (AT III, Protein C and Protein S), increased resistance to activated protein C,
      defective fibrinolysis (basal and after stimuli), increased levels of clotting
      factors (fibrinogen, factor VII, factor VIII, etc.), increased and/or hyperactive
      platelets, increased whole blood and/or plasma viscosity, Antiphospholipid
      antibodies and presence of prothrombotic molecular defects like FV Leiden, P20210
      and MTHFR. Approximately 4% and 2% respectively of Caucasians are heterozygous
      for these gene defects. Their causative role in neonatal thrombosis is unknown
      but they may have a contributory role in the pathogenesis of thrombosis in
      neonates.

PMID- 14703233
TI  - Neonatal adrenal hemorrhage with intraperitoneal spill managed conservatively.
AB  - A neonate presented with anemia, hyperbilirubinemia and bilateral flank fullness
      at 23 days of age. Ultrasound abdomen showed bilateral adrenal hemorrhage with
      intraperitoneal extension on the left side. This was managed nonoperatively and
      the hematoma resolved completely. Literature regarding this rare entity is
      described.

PMID- 14703232
TI  - Blood transfusion in newborn.
AB  - Premature infants are among the most frequently transfused groups of patients,
      usually receiving red cells. The immaturity of the immune system, its lesser
      ability to cope with a metabolic load and the presence of maternal antibodies,
      all complicate the picture. Conservation of blood to minimize losses and the need
      for replacement transfusion is an important strategy that has already been
      successful in reducing the need for transfusion on neonatal units. The advent of
      erythropoietin provides another strategy for reducing the need for transfusion.
      It is unfortunate that the sickest patients who require the most transfusion
      poorly respond to erythropoietin. Main concern is the long-term consequences of
      transfusion. Presently the aim is to minimize transfusion risks and give
      transfusions only when they are indicated.

PMID- 14703234
TI  - Kawasaki disease in India.
AB  - Kawasaki disease was first described 30 years ago. The authors report 5 children
      with Kawasaki disease who presented within 18-month-period and describe their
      clinical presentation and management.

PMID- 14703235
TI  - Losartan induced fetal toxicity.
AB  - Losartan is a specific angiotensin II receptor antagonist. Although the
      teratogenic effects of angiotensin converting enzyme (ACE) inhibitors are well
      documented there are limited reports of losartan induced fetal toxicity. The
      authors report a case of incomplete ossification of skull bones, transient
      oliguria and feed intolerance in a newborn following in-utero exposure to
      losartan.

PMID- 14703236
TI  - Candida tropicalis meningitis in a young infant.
AB  - Candida tropicalis is a rare species of Candida causing meningitis. The authors
      report a young infant who developed Candida tropicalis meningitis following a
      prolonged stay in a neonatal intensive care unit for respiratory distress and
      intra-cranial hemorrhage. The child was successfully treated with recommended
      doses of Amphotericin B and 5-flucytosine for eight weeks.

PMID- 14703238
TI  - Pulse polio immunization: a need for more inputs.

PMID- 14703237
TI  - Large tonsils and adenoids.

PMID- 14703239
TI  - Magnetic resonance imaging of the equine digit with chronic laminitis.
AB  - Chronic laminitis is a severe disease affecting the equine digit. It was
      hypothesized that magnetic resonance (MR) imaging would improve visualization of
      structures within the foot and pathology associated with chronic laminitis. This
      study aimed to describe the MR imaging findings in chronic laminitis, compare
      different pulse sequences for visualization of pathology, and to compare MR
      imaging with standard radiography. Twenty (10 forelimb, 10 hindlimb) cadaver
      limbs from 10 horses clinically diagnosed with chronic laminitis (group L) and 10
      limbs without laminitis (group N) were used. Lateromedial radiographs and
      sagittal and transverse MR images of the foot were obtained. Radiographs and MR
      images were evaluated for anatomic definition and evidence of pathology. Dorsal
      hoof wall thickness and angle of rotation and displacement distance of the distal
      phalanx were measured. Comparisons were made between group L and N, forelimb and
      hindlimb within each horse, and MR imaging and radiography. Features consistently
      noted with MR images in group L, but not detected using radiography, included
      laminar disruption, circumscribed areas of laminar gas, laminar fluid, and bone
      medullary fluid. Other findings seen only on MR images included increased size
      and number of vascular channels, alterations in the corium coronae, and distal
      interphalangeal joint distension. Magnetic resonance imaging allowed better
      definition of laminar gas lines and P3 surface irregularity observed on
      radiographs. Based on measurements, group L had a greater angle of rotation,
      distal displacement, and dorsal hoof wall thickness than group N; forelimb hoof
      wall thickness was greater than hindlimb; and distal displacement and hoof wall
      thickness measurements were smaller using MR imaging than radiography, but had a
      similar pattern. It is concluded that there are features of chronic laminitis
      consistently observed using MR imaging and that these may be additional to
      features observed radiographically.

PMID- 14703240
TI  - Comparison of computed tomography, tangential view radiography, and conventional
      radiography in evaluation of canine pelvic trauma.
AB  - Thirteen dogs with fractures requiring surgical repair were evaluated by standard
      two-view (i.e., lateral and ventrodorsal) radiography, tangential view (ventro 20
      degrees cranial-dorsocaudal [inlet] and ventro 20 degrees caudal-dorsocranial
      [outlet]) radiography, and computed tomography (CT). Radiographic and CT
      examinations were reviewed independently by the three authors, and specific
      anatomic sites were graded for the presence or possibility of lesions. The
      results of radiographic interpretations were compared to CT scan interpretations.
      Eighty-one percent of skeletal lesions detected by CT scans were diagnosed
      definitively radiographically. Differences between the interpretation of CT and
      radiographic examinations included abnormalities associated with soft-tissue
      structures (P < 0.0001), the sacroiliac joints (P = 0.02), and the acetabula (P =
      0.04). Interpretation of the lateral/ventrodorsal and inlet/outlet radiographic
      series were not statistically different, although inlet views may be
      complimentary to the standard radiographic examination. Its use deserves further
      study. Reader variation was less on evaluation of CT examinations than
      radiographic examinations. CT multiplaner reformations and three-dimensional
      reconstructions were useful for surgical planning in seven dogs. CT scanning is
      superior to survey radiography in assessing skeletal and soft-tissue injuries in
      dogs with pelvic trauma, although all clinically significant surgical lesions
      were described accurately radiographically. Based on this small series, the
      routine CT examination of dogs with pelvic trauma may not be justifiable for
      diagnosis but may be advantageous for surgical planning, especially if acetabular
      fractures are suspected on radiographs.

PMID- 14703241
TI  - Computed tomography of the normal lumbosacral intervertebral disc in 22 dogs.
AB  - Computed tomography of the lumbosacral spine was performed on 22 purpose-bred,
      medium-sized hound dogs between 1 and 6 years of age. Images were evaluated to
      determine the degree of disc bulge. All dogs were neurologically normal. Dogs
      were imaged in dorsal recumbency with the pelvic limbs variably extended.
      Sagittal reconstructions were made from transverse images. The mean (+/-SD) width
      of the mid-portion of the L7-S1 intervertebral disc was 0.5 +/- 0.07 cm (range
      0.33-0.62 cm). All L7-S1 intervertebral discs were dorsally convex, with the mean
      bulge measuring 0.25 +/- 0.07 cm (range 0.17-0.50 cm). The height of the
      vertebral canal at L7-S1 was 0.91 +/- 0.11 cm (range 0.68-1.15 cm). The mean
      percentage of the vertebral canal occupied by the bulge was 26.89 +/- 5.05%
      (range 20.74-43.08%). Mild bulging of the L7-S1 intervertebral disc can be
      present without associated neuropathy in medium-sized dogs.

PMID- 14703242
TI  - Use of computed tomography renal angiography for screening feline renal
      transplant donors.
AB  - Preoperative knowledge of the renal vascular anatomy is important for selection
      of the appropriate feline renal donor. Intravenous urograms (IVUs) have been
      performed routinely to screen potential donors at the Veterinary Hospital of the
      University of Pennsylvania (VHUP), but the vascular phase views lack sufficient
      detail of the renal vascular anatomy. Computed tomography angiography (CTA),
      which requires a helical computed tomography (CT) scanner, has been found to
      provide superior renal vascular anatomic information of prospective human renal
      donors. The specific aims of this study were as follows: 1) develop the CTA
      technique for the feline patient; and 2) obtain preliminary information on feline
      renal vessel anatomy in potential renal donors. Ten healthy, potential feline
      renal donors were anesthetized and imaged using a third-generation helical CT
      scanner. The time delay between i.v. contrast medium injection and image
      acquisition, and other parameters of slice collimation, slice interval, pitch,
      exposure settings, and reconstruction algorithms were varied to maximize contrast
      medium opacification of the renal vascular anatomy. Optimal CTA acquisition
      parameters were determined to be: 1) 10-sec delay post-i.v. bolus of iodinated
      contrast medium; 2) two serially acquired (corresponding to arterial and venous
      phases) helical scans through the renal vasculature; 3) pitch of 2 (4 mm/sec
      patient translation, 2 mm slice collimation); and 4) 120-kVp, 160-mA, and 1-sec
      exposure settings. Retrospective reconstructed CTA transverse images obtained at
      a 2-mm slice width and a 1-mm slice interval in combination with two-dimensional
      reformatted images and three-dimensional reconstructed images were qualitatively
      evaluated for vascular anatomy; vascular anatomy was confirmed at surgery. Four
      cats had single renal arteries and veins bilaterally; four cats had double renal
      veins. One cat had a small accessory artery supplying the caudal pole of the left
      kidney. One cat had a left renal artery originating from the aorta at a 90
      degrees angle with the cranial mesenteric artery. CTA of the feline renal
      vascular anatomy is feasible, and reconstruction techniques provide excellent
      anatomic vascular detail. CTA is now used routinely at VHUP to screen all
      potential feline renal donors.

PMID- 14703243
TI  - Effect of methylcellulose on upper gastrointestinal quality in dogs.
AB  - This study was performed to evaluate and optimize a small bowel contrast
      technique using barium and methylcellulose in dogs. Ten healthy dogs underwent
      both a conventional upper gastrointestinal study that used only barium and a
      modified study that used barium and methylcellulose. The control group received
      10 mL/kg of 40% barium suspension. Experimental groups were divided into three
      subgroups given 15 mL/kg of different viscosities (low, moderate, and high
      viscosity) of 0.5% methylcellulose after 4 mL/kg of 40% barium suspension.
      Compared with the control group, dogs receiving methylcellulose had higher
      quality upper gastrointestinal studies. Moderate viscosity of methylcellulose was
      superior to the other methylcellulose groups. In conclusion, the use of
      methylcellulose is a simple and effective method for improving the image quality
      in an upper GI examination.

PMID- 14703244
TI  - Type-4 esophageal hiatal hernia in a Chinese Shar-pei dog.
AB  - Thoracic radiography of a 3-month-old, female Chinese Shar-pei revealed an
      esophageal hiatal hernia with stomach, liver, and small intestine displaced into
      the thorax. Three days after the surgical correction, the dog developed ileal
      intussusception and was reoperated. Recovery was uncomplicated and the dog was
      asymptomatic 16 months after surgery.

PMID- 14703245
TI  - Inflammatory polyp in the middle ear with secondary suppurative
      meningoencephalitis in a cat.
AB  - A 15-month-old male Maine Coon Cat presented with persistent auricular discharge
      and progressive head tilt, ataxia, and loss of blink on the right side. Using
      computed tomography a hyperattenuating, contrast-enhancing material within a
      thickened right tympanic bulla and contrast enhancement of the adjacent
      cerebellum were identified. Marked suppurative inflammation was identified on
      cerebrospinal fluid analysis with no growth on bacterial culture. Ventral bulla
      osteotomy was performed to remove a soft tissue mass, and an inflammatory polyp
      with chronic severe suppurative inflammation was confirmed using histology.
      Staphylococcus auricularis was grown on aerobic culture and Fusobacterium
      necrophorum and Peptostreptococcus anaerobius were grown on anaerobic culture.
      The cat was treated for 10 weeks with amoxicillin/clavulinic acid and
      metronidazole. Dramatic improvement in body weight, appetite, energy level,
      balance, and resolution of right-sided facial paralysis were noted, but the cat
      retained a head tilt.

PMID- 14703246
TI  - Radiographic diagnosis: Intrathoracic gallbladder in a dog.

PMID- 14703247
TI  - Radiology corner: Lumbosacral radiography.

PMID- 14703248
TI  - Imaging diagnosis--Avulsion of the medial collateral ligament of the tarsus in a
      horse.

PMID- 14703249
TI  - Linear osteochondromatosis in a cat.
AB  - A domestic shorthair cat was presented with quadriparesis and lumbar
      hyperesthesia that progressed over 4 months. There were linear and amorphous
      radiopaque masses throughout the soft tissue surrounding the long bones,
      vertebral bodies, ribs, pelvis, and scapula. The diagnosis of osteochondromatosis
      was confirmed by histopathology. Unlike previously reported patients with
      osteochondromatosis, most of the calcified masses in this cat were not connected
      to the periosteum; some were linear and were arranged parallel to the long bones
      involved.

PMID- 14703250
TI  - Endoscopic ultrasound instrumentation, applications in humans, and potential
      veterinary applications.
AB  - Endoluminal scanning under endoscopic guidance, or endoscopic ultrasonography
      (EUS), has become the most significant advance for imaging the gastrointestinal
      (GI) tract wall and contiguous organs in the past 20 years. It was originally
      designed to overcome the limitations in humans to imaging the abdominal organs
      transabdominally, such as large penetration depths and GI air. This imaging
      modality provides detailed images of pathological processes both within and
      outside of the GI wall since a high-frequency transducer can be brought into
      close proximity with the target regions. It has found most success in humans for
      the staging of lung, gastric, and esophageal cancer, the detection of both
      lymphatic and hepatic metastases, and diagnosis of pancreatitis and pancreatic
      cancer, as well as achieving an important role in interventional and therapeutic
      procedures. The EUS examination can be performed to examine both the thorax and
      abdomen in animals when both conventional transthoracic or transabdominal
      ultrasound are inadequate due to intervening air, bone, large penetration depths,
      or obesity. The echoendoscope is similar to a conventional endoscope but has an
      ultrasound transducer at its tip. Both radial and linear multifrequency scanners
      are available. Linear scanners allow fine-needle aspiration (FNA) of the bowel
      wall or extraluminal structures. Transducer coupling is either by direct mucosal
      contact or by inflation of a water-filled balloon surrounding the transducer.
      Current thoracic applications for EUS in veterinary medicine include examination
      of the mediastinum, bronchial lymph nodes, esophagus, and pulmonary lesions as
      well as FNA of pulmonary masses. Abdominal applications include examination of
      both pancreatic limbs and the liver, including portosystemic shunts, detection of
      lymphadenomegaly, and examination of the gastric wall, duodenum, and jejunum.
      Other potential applications in dogs and cats include tumor staging and
      intrapelvic ultrasound.

PMID- 14703251
TI  - Changes in ultrasonographic appearance of adrenal glands in dogs with pituitary
      dependent hyperadrenocorticism treated with trilostane.
AB  - Trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, has been used
      successfully over the last few years for the treatment of canine pituitary
      dependent hyperadrenocorticism. In a prospective study of 19 dogs with pituitary
      dependent hyperadrenocorticism, the adrenal glands were measured before and at
      least 6 months after initiation of trilostane therapy. Right adrenal gland length
      and caudal pole thickness and left adrenal gland caudal pole thickness increased
      significantly (p < or = 0.05); there was no significant change in left adrenal
      gland length. Enlargement of adrenal glands during trilostane therapy may occur
      as a result of suppression of the negative feedback mechanism affecting cortisol
      production.

PMID- 14703252
TI  - Relationship among basilar artery resistance index, degree of ventriculomegaly,
      and clinical signs in hydrocephalic dogs.
AB  - Forty-four transcranial Doppler ultrasound studies were performed in 36 dogs. The
      ratio of the height of the ventricle to the height of the brain (VB ratio) was
      calculated to determine the severity of ventriculomegaly. Resistance index (RI)
      was calculated from Doppler measurements of the blood flow velocity in the
      basilar artery and neurologic signs were scored on a scale of 0 to 3. Based on
      clinical and ultrasonographic findings, dogs were divided into four groups
      (normal controls, asymptomatic hydrocephalus, symptomatic hydrocephalus, and
      other intracranial disease). RI and VB ratio were compared between the groups of
      dogs and compared with neurologic signs in hydrocephalic dogs. RI ranged from
      0.50 to 0.81 (mean, 0.68). Resistance index was significantly higher in dogs with
      symptomatic hydrocephalus and other intracranial disease when compared with the
      other two groups. The degree of ventriculomegaly was significantly higher in dogs
      with symptomatic hydrocephalus than the other groups, but there was substantial
      overlap between asymptomatic and symptomatic hydrocephalus groups. Combining
      measurements of VB ratio and RI allowed detection of symptomatic hydrocephalus
      with a sensitivity of 77% and a specificity of 94%. The severity of neurological
      signs was significantly correlated with RI and with VB ratio in hydrocephalic
      dogs, and in dogs evaluated on more than one occasion, changes in neurologic
      status were accompanied by changes in RI but not in VB ratio. All asymptomatic
      hydrocephalic dogs with a VB ratio of greater than 60% eventually developed
      neurologic signs. Our results suggest that ultrasonographic measurement of VB
      ratio and basilar artery RI may allow identification of dogs with symptomatic
      hydrocephalus or dogs that are at risk of developing symptomatic hydrocephalus.
      Repeated RI measurements are a useful means of monitoring dogs with a variety of
      intracranial diseases.

PMID- 14703253
TI  - Comparison of Doppler-derived peak aortic velocities obtained from subcostal and
      apical transducer sites in healthy dogs.
AB  - The accuracy of Doppler-derived blood flow velocity depends on the angle of
      incidence between the ultrasound beam and the direction of flow. In dogs with
      subaortic stenosis, it is known that the subcostal transducer site provides
      higher left ventricular ejection velocities than does the apical site. Left
      ventricular ejection velocities obtained from the subcostal site in healthy dogs
      have not been reported; accordingly, we examined healthy, random-source dogs to
      test the hypothesis that aortic velocities obtained from the subcostal and apical
      transducer sites differ. In 38 unsedated dogs, high-pulsed repetition frequency
      (HPRF) and continuous-wave (CW) Doppler studies of the proximal aorta and left
      ventricular outflow tract were performed using two-dimensional echocardiographic
      guidance. The effects of Doppler modality, transducer site, and their interaction
      on peak aortic velocity were tested through the use of analysis of variance. P
      values less than 0.05 were considered to indicate significance. The mean (+/-SE)
      peak aortic velocities were as follows: subcostal site (HPRF) = 1.44 +/- 0.03;
      apical site (HPRF) = 1.39 +/- 0.03; subcostal site (CW) = 1.48 +/- 0.03; apical
      site (CW) = 1.39 +/- 0.03. Aortic velocities obtained from the subcostal site
      were significantly greater than those obtained from the cardiac apex (P =
      0.0001). Lower and upper limits of 95% reference intervals for aortic velocities
      by method of measurement and transducer location are proposed. In a population of
      healthy dogs, peak aortic velocities obtained from the subcostal site exceeded
      those obtained from the cardiac apex but did so only to a marginal degree.

PMID- 14703254
TI  - Scintigraphy of the sacroiliac joint region in asymptomatic riding horses:
      scintigraphic appearance and evaluation of method.
AB  - The sacroiliac region in 33 clinically normal riding horses was examined with
      scintigraphy to determine the normal scintigraphic appearance, to evaluate a
      semiquantitative method used to calculate a sacroiliac joint (SI joint) ratio,
      and to identify factors that affect the scintigraphic appearance of the pelvis.
      The scintigraphic examination included dorsal views of each SI joint region and
      one lateral view of the urinary bladder. Two predefined areas (the SI joint and
      the area between the tuber sacrale and the SI joint) were evaluated subjectively
      by comparing the intensity in each area to the intensity in the tuber sacrale,
      and a semiquantitative method was applied on the images to calculate an SI joint
      ratio. The thickness of the muscle mass overlying each SI joint was measured by
      using ultrasound. A corrected ratio was calculated based on a corrected pixel
      count for each SI joint. Of 29 evaluated horses, 28 had normal radiotracer uptake
      in the SI joints and 10 horses had symmetric normal radiotracer uptake in the
      area between the tuber sacrale and the SI joint. The mean SI joint ratio was 0.53
      on both the left and right sides, and the mean corrected SI joint ratio was 2.15
      on the left side and 2.13 on the right side. Factors that affect the
      scintigraphic appearance of the pelvis were identified and included attenuation,
      radioactive urine, and muscle symmetry. The muscle thickness ranged from 8-11 cm,
      causing 71-82% attenuation. Radioactive urine in the urinary bladder was located
      ventral to the SI joint region in 16 horses, and four of these were excluded from
      further evaluation because of risk of misinterpretation. A visual assessment of
      symmetry of the horses' gluteal muscle mass was compared with the ultrasound
      measurements. Fourteen horses (14/33) were regarded symmetric by both techniques.
      Soft tissue attenuation was found to severely compromise the result and indicated
      that only lesions in the SI joint with severely increased radiotracer uptake can
      be detected with scintigraphy. Knowledge about presence of radioactive urine
      ventral to the SI joint region and assessment of muscle symmetry is essential for
      a correct subjective evaluation. Any situation with difference in muscle mass
      between the left and right side of the pelvis will give a false impression of
      increased radiotracer uptake on the side with lesser muscle mass.

PMID- 14703255
TI  - Sonographic and scintigraphic evaluation of acute renal allograft rejection in
      cats.
AB  - The sonographic features of acute renal allograft rejection in humans and dogs
      are manifested by increase in renal cross-sectional area and reduction in renal
      cortical blood flow. These changes have not been investigated in cats. The
      objectives of this study were to evaluate sonographic and scintigraphic changes
      during acute renal allograft rejection in cats. Eight SPF, intact, adult, male
      cats received heterotopic renal allotransplantations. Immunosuppressive doses of
      cyclosporine and prednisolone were administered for 14 days and then discontinued
      to allow acute allograft rejection to occur. Serial measurements of renal cross
      sectional area, resistive index (RI), echogenicity, and glomerular filtration
      rate (GFR) were performed to evaluate changes during acute rejection. Upon
      sonographic confirmation of absent diastolic blood flow or a 20% increase in
      cross-sectional area of the allograft, a nephrectomy and histopathologic
      evaluation were performed. Acute allograft rejection was confirmed histologically
      in all cats. Significant increases in renal cross-sectional area (P < 0.001)
      occurred postoperatively and during rejection. There were no significant changes
      in RI (P = 0.43) at any time. A subjective increase in medullary echogenicity and
      a decrease in corticomedullary demarcation were observed in the rejection period.
      While GFR decreased significantly in the immediate postoperative period (P <
      0.001), no further change occurred during rejection (P = 0.42). Changes in RI and
      GFR do not appear to be sensitive indicators of acute renal allograft rejection
      in cats. Serial measurements of renal cross-sectional area appear to be a
      sensitive method for the early diagnosis of allograft rejection in feline renal
      transplant recipients.

PMID- 14703256
TI  - Accuracy of positioning the cervical spine for radiation therapy and the
      relationship to GTV, CTV and PTV.
AB  - The purpose of the study was to evaluate the accuracy and precision of a rigid
      positioning device for repositioning the cervical spine accurately and precisely
      during conformal radiation therapy of dogs. Fifteen purpose bred research dogs in
      a radiation therapy study were included. The dogs were positioned using a head
      holder and a deflatable pillow attached to the treatment table. Port films were
      reviewed retrospectively, and repositioning precision was recorded by
      measurements in three orthogonal planes of the head, 2nd cervical vertebra and
      1st thoracic spinous process. Mean treatment position was compared to the
      planning position for a measurement of systematic set-up error. Mean
      interfraction position variation of the 2nd cervical vertebra was 0.2, 0.1 and
      0.2 cm for the ventrodorsal, caudocranial and laterolateral directions
      respectively, and the average systematic set up error was 0.2, 0.1 and 0.2 cm for
      the ventrodorsal, caudocranial and laterolateral directions respectively.
      Knowledge of the magnitude of reposition errors should be included when
      determining the margins around the tumor.

PMID- 14703257
TI  - Tribal participatory research: mechanisms of a collaborative model.
AB  - Although much social science research has been conducted within American Indian
      and Alaska Native (AIAN) communities, relatively little research has been
      conducted by or for those communities. We describe an approach that facilitates
      the active involvement of AIAN communities in the research process, from
      conceptualizing the issues to be investigated to developing a research design,
      and from collecting, analyzing, and interpreting the data to disseminating the
      results. The Tribal Participatory Research (TPR) approach is consistent with
      recent developments in psychology that emphasize the inclusion of community
      members and the social construction of knowledge. We describe the foundations of
      the approach and present specific mechanisms that can be employed in
      collaborations between researchers and AIAN communities. We conclude with a
      discussion of the implications of the use of TPR regarding project timelines and
      budgets, interpretation of the data, and ultimately the relationships between
      tribes and researchers.

PMID- 14703258
TI  - The influence of cultural and racial identification on the psychosocial
      adjustment of inner-city African American children in school.
AB  - The purpose of this study was to examine the relationship and combined influence
      of racial identity and Africentric values on African American children's
      psychosocial adjustment. Participants were 104 (53 males, 51 females) African
      American fourth-grade students attending an inner-city public school in a
      northeastern city. Child and teacher ratings were used to assess the relationship
      between racial identity, Africentric values, and several indices of child
      psychosocial adjustment, including child behavior control, school interest, and
      teacher perceptions of child strengths and problems in the classroom. Child self
      esteem and the effects of gender and cohort were used as covariates in several
      analyses in the study. Overall, findings from the study supported the usefulness
      of combining racial identity and Africentric values into a single model of ethnic
      identification for African American children. Implications for risk prevention
      and enhancement of psychosocial functioning among African American children are
      discussed.

PMID- 14703259
TI  - Reconceptualizing quantitative and qualitative methods: a case study dealing with
      place as an exemplar.
AB  - A useful framework for understanding methods is to think of them as being on a
      continuum of holistic and pattern focused to particularistic and specific. This
      paper argues for this conceptualization rather than thinking of quantitative and
      qualitative methods as oppositional and potentially contradictory. A case study
      provides an example of using both quantitative and qualitative methods in a
      holistic and pattern-focused study, while also attending to the values and goals
      of community psychology. The substantive research goal is to understand a child's
      experience of places related to school. Methods include ethnographic long-term
      participation and observation, interviews, multidimensional scaling, and social
      network analysis. Most quantitative method variables are generated from study
      participants; no outside structure is imposed. The quantitative methods extend
      and inform the qualitative methods, just as the qualitative methods extend and
      inform the quantitative methods. The quantitative and qualitative methods work
      reciprocally to extend and inform each other.

PMID- 14703260
TI  - A multilevel contextual model of neighborhood collective efficacy.
AB  - Different data sources were used to examine hypothesized relations among
      neighborhood-, family-, and individual-level variables, and perceptions of
      neighborhood collective efficacy. Data were from 1,105 individuals (56% female,
      42% African American, and 58% White) nested within 55 neighborhoods and 392
      families, analyzed within a multilevel design using a 3-level model. At the
      neighborhood level, the study examined relations between Census, police, and
      neighborhood representative indicators. At the family level, the model examined
      the influence of marital status and family income. At the individual level,
      gender and age were examined. Results indicated that age at the individual level,
      marital status at the family level, and poverty and perceived gang activity at
      the neighborhood level predicted levels of neighborhood collective efficacy. The
      study illustrated significant variation across neighborhoods and families, and
      demonstrates the utility of combining different sources of neighborhood data to
      examine relations of interest within a multilevel framework.

PMID- 14703261
TI  - Moving beyond the individual: examining the effects of domestic violence policies
      on social norms.
AB  - To be effective, criminal justice policies should affect the underlying social
      norms for which the policies were enacted. This study sought to determine whether
      public perceptions of criminal justice policies on domestic violence affected
      social norms. Two waves of data were collected via a telephone survey where a
      random probability sample of 973 residents was drawn from 4 communities. A
      structural equation model was tested and confirmed. Results provided strong
      support for the hypothesis that perceptions of criminal justice policies have
      direct effects on attitudes toward criminal justice response, and indirect
      effects on victim-blaming attitudes, both underlying social norms related to
      domestic violence. The enactment of criminal justice policies, therefore, may
      have an impact beyond victims and perpetrators and lead to a transformation of
      the community through the emergence of new social norms. Public awareness
      campaigns designed to disseminate criminal justice policies may be instrumental
      in provoking social change.

PMID- 14703262
TI  - Social distribution of social support: the mediating role of life events.
AB  - Although the relation of socioeconomic status (SES) to social support has been
      discussed for some time, researchers have rarely systematically examined the
      social patterning of this resource. In addition, potential explanatory mechanisms
      have not been investigated. This study examined both the social distribution of
      social support and the role of life events in the association between SES and
      social support in a nationally representative probability sample of adults from
      the National Cormorbidity Survey. Higher education and income were related to
      more emotional support and fewer negative interactions. Individuals with higher
      incomes were also less likely to report acute and chronic life events. Finally,
      acute (but not chronic) life events mediated the relation between SES and social
      support (both emotional support and negative interactions). These results suggest
      the inability of lower SES individuals to mobilize social support in times of
      need may be explained by their more frequent experience of acute life events.

PMID- 14703263
TI  - Anansi and how the moon got put in the sky.

PMID- 14703264
TI  - Experimental social innovation and dissemination: the promise and its delivery.
AB  - This paper describes the origin of the Experimental Social Innovation and
      Dissemination model and its contribution to and intersection with community
      psychology. It also discusses the challenges presented to ESID by community
      psychology's growing emphasis on cultural diversity and participatory approaches
      to research and intervention. It concludes with an overview of the papers
      presented in the special issue.

PMID- 14703265
TI  - Using the ESID model to reduce intimate male violence against women.
AB  - Described how the Experimental Social Innovation and Dissemination (ESID) model
      was successfully used to reduce intimate male violence against women. Following
      the principles of ESID, the experimental social innovation involved providing
      trained paraprofessional advocates to work one-on-one with women who had been
      assaulted by partners or ex-partners. Advocates worked with women for 10 weeks,
      assisting them in obtaining needed community resources such as legal assistance,
      housing, education, and employment. Two hundred seventy eight women who had
      exited a domestic violence shelter program were randomly assigned to the
      experimental or control condition. Participants were interviewed 6 times over a
      period of 2 years: pre- and postintervention (10 weeks later), and at 6, 12, 18,
      and 24-month follow-up. Women who received the intervention reported less
      violence over time as well as higher social support and perceived quality of
      life. The relevance of the ESID model in addressing this as well as other
      significant social problems is discussed.

PMID- 14703266
TI  - Consumer preference programs for individuals who are homeless and have
      psychiatric disabilities: a drop-in center and a supported housing program.
AB  - We illustrate Fairweather's approach to Experimental Social Innovation and
      Dissemination with two experimental studies of programs to reduce homelessness
      for 168 and 225 people with mental illness and often substance abuse. Literally
      homeless participants were randomly assigned to programs that emphasized consumer
      choice or to the usual continuum of care, in which housing and services are
      contingent on sobriety and progress in treatment. A drop-in center that
      eliminated barriers to access to services was more successful than control
      programs in reducing homelessness, but after 24 months only 38% of participants
      had moved to community housing. A subsequent apartment program, in which
      individuals in the experimental condition moved to subsidized apartments directly
      from the street, with services under their control, had 79% in stable housing
      (compared to 27% in the control group) at the end of 6 months. Groups in this
      study did not differ on substance abuse or psychosocial outcomes.

PMID- 14703267
TI  - A modified ESID approach to studying mental illness and homelessness.
AB  - This paper describes 15 years of research on homelessness using a modified ESID
      approach. The article summarizes the results of several needs assessment studies;
      describes the development and evolution of alternative treatment models to assist
      homeless individuals with severe mental illness; summarizes results of three
      outcome evaluation studies; and discusses issues of treatment implementation,
      treatment diffusion, and dissemination.

PMID- 14703268
TI  - HIV, sex, and social change: applying ESID principles to HIV prevention research.
AB  - The HIV epidemic has been the most significant public health crisis of the last 2
      decades. Although Experimental Social Innovation and Dissemination (ESID)
      principles have been used by many HIV prevention researchers, the clearest
      application is the series of model-building and replication experiments conducted
      by Kelly and colleagues. The model mobilized, trained, and engaged key opinion
      leaders to serve as behavior change and safe-sex endorsers in their social
      networks. This paper illustrates how ESID principles were used to develop, test,
      and disseminate an innovative social model and discusses the challenges of
      applying ESID methodology in the midst of a public health emergency.

PMID- 14703269
TI  - An ESID case study at the federal level.
AB  - The D (dissemination) phase of the ESID model has been often overlooked in our
      efforts to create innovative and widespread social change. The process of
      replicating successful social innovations is both a prerequisite for
      dissemination (in order to assess the consistency of effects) and an obvious
      outcome of a successful dissemination effort. Fidelity, the extent to which a
      replicated program is implemented in a manner consistent with the original
      program model, is an important dimension of replication. This study was designed
      to provide empirical data related to three questions. Can complex social programs
      be implemented with fidelity? How much fidelity is appropriate or desired? What
      are the organizational dynamics of adoption with fidelity? Data were collected
      from grantees of a national replication initiative funded by the Center for
      Substance Abuse Prevention. Data suggest that high fidelity can be achieved, at
      least in the context in which programs are mandated to do so as part of the
      funding agreement and are given technical assistance in achieving fidelity.
      Secondly, programs perceived high fidelity as having positive effects on the
      program and its participants, a finding consistent with a limited assessment of
      the relationship of program outcomes and fidelity. Finally, much was learned
      about the human and organizational dynamics of replicating with fidelity.
      Implications for policy and direction regarding replication are discussed.

PMID- 14703270
TI  - ESID, dissemination, and community psychology: a case of partial implementation?
AB  - Dissemination, the second stage of Experimental Social Innovation and
      Dissemination (ESID) is a critical, if not defining, element of this social
      change model. This paper attempts to assess the extent to which community
      psychology has adopted and implemented ESID's dissemination focus in its training
      and publications. We identify four levels of commitment to dissemination:
      dissemination advocate, dissemination activist, dissemination researcher, and
      experimental dissemination researcher. Content analyses of textbooks, journal
      publications, and conference papers and a brief survey of doctoral training in
      the field were conducted. Findings suggest that the dissemination aspects of ESID
      have been modestly and partially implemented within the field. That is, although
      there is some evidence of a commitment to dissemination practice (advocate,
      activist), there is much less evidence of a commitment to dissemination research.
      The implications of these findings for the effectiveness of the ESID model and
      for training and practice in community psychology are discussed.

PMID- 14703271
TI  - Fairweather and ESID: contemporary impact and a legacy for the twenty-first
      century.
AB  - This paper illustrates how the articles in this special issue demonstrate the
      central values, research, and action principles inherent in Fairweather's ESID
      model. The programs described in these articles address earlier social problems
      in new forms (e.g., previously, institutionalized mentally ill patients and now,
      the homeless mentally ill) and new issues (e.g., HIV prevention). Dissemination
      of innovative programs is abundant, but only recently has research begun in
      earnest to study the critical processes of dissemination. Moreover, Fairweather
      has pointed us in important, but yet unrealized directions for how to pursue a
      theory of social change on the basis of ecological concepts, innovative research
      methods and data analytic techniques, and salient change agent behaviors and
      principles.

PMID- 14703272
TI  - Surgery of intractable temporal lobe epilepsy presented with structural lesions.
AB  - BACKGROUND: Structural lesions are found in about 30% of surgical specimens
      resected for intractable temporal lobe epilepsy (TLE). Detailed presurgical
      evaluations can identify the epileptogenic foci, the structural lesions and their
      correlation. Different surgical approaches have variable seizure control
      outcomes. METHODS: The preoperative investigations for the intractable TLE
      consisted of serial electroencephalogram (EEG) recordings, long-term EEG/video
      monitoring with sphenoidal electrodes, magnetic resonance imaging (MRI), magnetic
      resonance spectroscopy (MRS), positron emission tomography with
      fluorodeoxyglucose (FDG-PET) and neuropsychological assessment. Among the 217
      patients who underwent anterior temporal lobectomy (ATL) for TLE at Taipei
      Veterans General Hospital between 1987 and 1998, 47 (21.7%) had structural
      lesions in the resected specimen. The patients were divided into neoplastic (n =
      35) and vascular (n = 12) groups, based on the pathological findings. RESULTS: In
      the neoplastic group, the interictal scalp-sphenoidal EEG recordings were
      abnormal in all 35 cases and lateralizing in 30 (85.7%). MRI revealed tumor
      growth within the temporal lobe in 26 patients (74.3%). FDG-PET was performed on
      17 patients. Fifteen (88.2%) of them revealed unilateral mesial temporal lobe
      hypometabolism. In the vascular group, the interictal EEG tracings revealed
      unilateral mesial temporal lobe spikes in 11 patients (91.6%). MRI revealed
      abnormal enhanced lesions within the temporal lobes in all 12 patients. FDG-PET
      was available for 7 patients, 6 (86%) of whom had unilateral mesial temporal lobe
      hypometabolism. At the last follow-up (range 2-10 years, with a mean period of
      4.2 years), 25 patients (73%) in the neoplastic group became and remained seizure
      free postoperatively, 3 (9%) had fewer than 3 attacks per year. Among the
      vascular group, all 12 patients became and remained seizure-free after surgery.
      CONCLUSIONS: For intractable TLE with structural lesions, detailed presurgical
      evaluations are mandatory to identify the concordance of the lesions and the
      epileptogenic foci. Standard ATL with removal of the lesion may offer good
      seizure control postoperatively.

PMID- 14703273
TI  - Evaluation of exercise prescription for hypertensive obese men by ventilatory
      threshold.
AB  - BACKGROUND: Prescription of aerobic exercise for obese subjects with mild
      hypertension in clinical practice remains to be investigated. METHODS: Forty-one
      Japanese obese males with hypertension were enrolled and compared with 41 age-and
      sex-matched obese subjects without hypertension and control subjects. In
      addition, 25 obese subjects with or without hypertension participated in a one
      year follow up study. They were instructed to keep their low exercise intensity
      and record their daily walking. Before and after exercise prescription, body
      composition, blood pressure and aerobic exercise level were evaluated.
      Ventilatory threshold (VT) was determined breath by breath during exercise test
      using a ramp protocol and rates of oxygen consumption (VO2), work rate (WR),
      heart rate (HR), deltaHR, %HR max, %HR reserve and rate of perceived exertion
      (RPE) were measured at VT. RESULTS: At VT, obese subjects with hypertension had
      significantly lower VO2 (13.5 +/- 2.1 mL/kg/min) and WR (75.1 +/- 16.5W) than
      control subjects (VO2, 18.1 +/- 5.7; WR, 92.0 +/- 32.4). %HR reserve was also
      significantly lower compared with control subjects, while %HR max, was not
      different. RPE was also similar among the 3 groups. By prescribed low-grade
      exercise during one-year follow-up study, not only body composition but also
      blood pressure at rest was improved in obese subjects with and without
      hypertension. CONCLUSIONS: Our results indicated reduced exercise capacity in
      Japanese obese males. Exercise intensity of 60%HR max, 30%HR reserve and RPE 12
      is recommended in obese subjects with hypertension as well as obese subjects
      without hypertension.

PMID- 14703274
TI  - Risk factors for spontaneous bacterial empyema in cirrhotic patients with
      hydrothorax.
AB  - BACKGROUND: Spontaneous bacterial empyema (SBEM) is a rare complication of portal
      hypertension. The characteristics and risk factors for SBEM are not well known.
      This study was performed to investigate the risk factors for SBEM in cirrhotic
      patients with hydrothorax. METHODS: From July 1996 to December 1998, 862
      cirrhotic patients were studied. All patients underwent chest radiography,
      abdominal sonography or computed tomography after admission to detect the
      existence of pleural effusion. Pleural fluid was obtained after thoracentesis and
      sent for analysis. The clinical and laboratory data from patients with sterile
      hydrothorax and from SBEM at the time of first episode were compared. RESULTS:
      Seventeen patients had 26 episodes of SBEM during the study period, 56% (14 of
      26) of these SBEM episodes were associated with spontaneous bacterial peritonitis
      (SBP) and 31% (8 of 26) were associated with bacteremia. The incidence of SBEM
      was 2% (17 of 862) in cirrhotic patients and 13% (17 of 132) in cirrhotics with
      hydrothorax. Patients with SBEM had a higher Child-Pugh score, lower serum
      albumin, prolonged prothrombin time, lower pleural fluid protein, and higher rate
      of associated SBP than patients with sterile hydrothorax. Multivariate analysis
      revealed that pleural fluid protein level (p = 0.0035) and presence of SBP (p =
      0.0062) were predictive factors of SBEM. The hospitalization mortality rate of
      SBEM was 38%. CONCLUSIONS: Patients with advanced liver disease, low pleural
      fluid protein level, or SBP are predisposed to SBEM. A diagnostic thoracentesis
      should be performed in cirrhotic patients with pleural effusion when infection is
      suspected or clinical deterioration occurs.

PMID- 14703275
TI  - Using electrodiagnostic machine to study movement rhythm variation.
AB  - BACKGROUND: Hand movement constitutes the most common daily activities in our
      life. Hand dexterity is often impaired in patients with neurological disease. We
      developed an adjunct method, based upon the electrodiagnostic software, for study
      of motor control and hand dexterity. METHODS: Thirty-two normal subjects, 2
      stroke patients and 2 Parkinson patients were included in the study. All of them
      were right-handed, and were asked to pace rhythmic finger tapping at a
      comfortable rate without cue or any external stimuli. A trigger kit was designed
      to transform the finger tapping. After using the triggering mode and adjusting
      the sweep speed, 2 tapping signals were simultaneously displayed on the screen.
      The first signal was the triggering potential, and the variation in timing of the
      second signal represented the variation in timing of the inter-response interval.
      Twenty sweeps were recorded, superimposed and measured on the screen. Movement
      rhythm variation (MRV) was defined as b/a x 100 (b = [maximal interval of finger
      tapping - minimal interval of finger tapping]; a = [maximal interval of finger
      tapping + minimal interval of finger tapping]/2). Each subject started with right
      hand and then left hand. RESULTS: MRV measurement showed excellent intrarater (r
      = 0.97) and interrater (r = 0.97) reliability. In normal right-handed subjects,
      the MRV was better in right hand than in left hand (right 16.5 +/- 4.1% and left
      21.0 +/- 7.6%; p < 0.05). The MRV improved in stroke patients along with the
      recovery and improved in Parkinson patients after levodopa treatment.
      CONCLUSIONS: MRV was a good method to provide quantitative data for assessment of
      hand dexterity. Our study also showed the potential role of MRV in motor control
      study.

PMID- 14703276
TI  - Increased serum concentrations of tumor necrosis factor-alpha are associated with
      disease progression and malnutrition in hepatocellular carcinoma.
AB  - BACKGROUND: Increased serum tumor necrosis factor-alpha (TNF-alpha)
      concentrations are associated with disease progression in some cancers. Also, TNF
      alpha is known as an important mediator of cancer cachexia. This study was
      conducted to investigate the relationship between serum TNF-alpha levels and
      disease and nutritional status in patients with hepatocellular carcinoma.
      METHODS: Thirty-one male cirrhotic patients with hepatocellular carcinoma (mean
      age: 65 +/- 2 years), 26 male cirrhotic patients without hepatocellular carcinoma
      (mean age: 59 +/- 3 years), and 25 male control subjects (mean age: 67 +/- 2
      years) were included. Body fat mass was examined by bioelectrical impedance
      analysis. Serum TNF-alpha levels were measured by immunoassay. Hepatocellular
      carcinoma progression was staged by Okuda's classification. RESULTS: Serum TNF
      alpha values in 31 patients with hepatocellular carcinoma and 26 patients with
      cirrhosis were significantly above those of controls (12.3 +/- 0.7 pg/mL vs. 11.3
      +/- 1.2 pg/mL vs. 5.8 +/- 0.7 pg/mL; p < 0.01), but showed no differences between
      hepatocellular carcinoma and cirrhotic patients. When hepatocellular carcinoma
      patients were grouped according to Okuda's classification, the serum TNF-alpha
      levels significantly increased with disease progression (p < 0.05). Only in
      patients at stage III (n = 5), but not at stages I (n = 13) and II (n = 13), was
      the serum TNF-alpha levels greater than those in cirrhotic patients (p < 0.05).
      The serum albumin values and body fat mass in patients with hepatocellular
      carcinoma were both lower than in controls [(34 +/- 1 g/L vs. 42 +/- 1 g/L; p <
      0.01); (15.9 +/- 1.2 kg vs. 18.9 +/- 0.8 kg; p < 0.05), respectively]. Further,
      both decreased significantly with disease progression by Okuda staging [(37 +/- 1
      g/L vs. 32 +/- 2 g/L vs. 30 +/- 1 g/L; p < 0.01); (19.4 +/- 1.6 kg vs. 13.9 +/-
      1.8 kg vs. 11.7 +/- 2.0 kg; p < 0.05); respectively]. Finally, a negative
      correlation was found between serum TNF-alpha and both fat mass (p = -0.40; p <
      0.05) and serum albumin (p = -0.45; p < 0.05). CONCLUSIONS: Our study
      demonstrated that serum TNF-alpha levels were increased in patients with
      hepatocellular carcinoma, and associated with disease severity and nutrition
      status. However, serum TNF-alpha should not be used as a marker to early diagnose
      hepatocelluar carcinoma in cirrhotic patients.

PMID- 14703277
TI  - Weight-for-height reference and the prevalence of obesity for school children and
      adolescents in Taiwan and Fuchien Areas.
AB  - BACKGROUND: Overweight and obesity in childhood and adolescence are recognized as
      public health problems worldwide. Updated growth reference values of weight-for
      height are needed for monitoring physical growth of children and adolescents.
      METHODS: Weight-for-height and the prevalence of obesity for school children and
      adolescents in Taiwan and Fuchien Areas were analyzed based on the data obtained
      in a 2002 nationwide survey of 86,967 subjects, including 44,133 boys and 42,834
      girls, ages 6.5 to 18.5 years. Weight-for-height percentile curves were smoothed
      separately by regression model with polynomials. RESULTS: The growth reference
      values of weight-for-height were updated for monitoring physical growth. The
      prevalence of childhood and adolescent obesity was 18.5% (range: 10.6%-22.8%) in
      boys and 15.0% (range: 10.0%-18.4%) in girls. Boys had a higher prevalence of
      obesity than girls did at all ages. The peak of prevalence of obesity in boys was
      around 10.0-12.0 years old. CONCLUSION: At all ages, the prevalence of childhood
      and adolescent obesity for both sexes is higher in the 2002 than in 1997. This
      evidence strongly suggests an increasing prevalence of obesity during childhood
      and adolescence in recent years, irrespective of sex.

PMID- 14703278
TI  - Retained rectal foreign bodies.
AB  - BACKGROUND: Retained rectal foreign bodies have been encountered more frequently
      and present a dilemma for management. Most of the reports on these cases were
      documented in the form of case report and from Western countries. The present
      study was a review on the authors' experiences in such cases. METHODS: Data from
      January 1979 to January 2000 were extracted from a computerized database of
      Taipei Veterans General Hospital. The clinical features, treatment strategies and
      outcomes were analyzed. RESULTS: Ten male patients (mean age: 57.0 years) with 12
      presentations of retained rectal foreign bodies were collected. Glass bottles and
      vibrators were the most common objects encountered, while anal eroticism was
      reported as the reason for insertion in 50% of the cases. The majority of the
      objects were extracted by non-surgical methods through either anoscope (n = 4),
      rigid sigmoidoscope (n = 2) or colonoscope (n = 1). Obstetric forceps was
      utilized to remove an incarcerated bowling bottle. Emergent laparotomies were
      performed in cases with overt peritonitis (n = 2), pelvic sepsis (n = 1) and an
      impacted high-lying glass bottle. Minor complications, such as mucosal abrasion
      or superficial tear, were found in 62.5% of the non-surgically treated cases.
      Delayed bleeding was found in 2 of them. There was no mortality in our series.
      CONCLUSIONS: Despite its rarity, the retained rectal foreign body had varying
      clinical features. Most of the uncomplicated rectal foreign bodies could be
      simply extracted transanally under adequate anesthesia. Fiberoptic colonoscopic
      extraction provided an alternative choice. Open surgery should be reserved only
      for those patients with overt peritonitis or pelvic sepsis.

PMID- 14703279
TI  - Echocardiographic features of tuberculous pericarditis.
AB  - Echocardiography is a sensitive diagnostic tool for detecting pericardial
      effusion and intrapericardial abnormalities. A-70-year old man was found to have
      tuberculous pericarditis. The history and echocardiographic findings are
      reported, and relevant literature is reviewed.

PMID- 14703280
TI  - Pseudomonas aeruginosa endocarditis associated with endophthalmitis caused by
      arteriovenous fistula and graft infection.
AB  - Bacterial endocarditis due to Pseudomonas aeruginosa arising from arteriovenous
      (AV) fistula and graft infection is unusual. We report an uncommon case of a 55
      year-old woman housewife with chronic glomerulonephritis who had received
      hemodialysis (HD) for 5 years. She was admitted due to frequent episodes of AV
      fistula and graft infections in the past 5 years. She was admitted to our
      hospital because of a fever of unknown origin. During hospitalization, cardiac
      sonography and transesophageal echocardiography (TEE) confirmed a vegetation over
      the mitral valve. Blood culture yielded Pseudomonas aeruginosa. Endophthalmitis
      of the right eye was diagnosed by funduscopy because of painful redness of the
      right eye with exudative discharge. The patient was treated with ceftazidime for
      9 weeks. Since then, she has been well, without any sequale after 1 year of
      following up. Physicians should be aware of the possibility of infective
      endocarditis in an uremic patient who suffers from fever of unknown origin. Early
      diagnosis with an adequate tool such as TEE and appropriate treatment will lead
      to an excellent prognosis.

PMID- 14703281
TI  - Managements of complicated otitic abscess.
AB  - The advent of antibiotics has significantly reduced the incidence and associated
      morbidity of otogenic complications. Its presentation, however, has dramatically
      changed and appears as a masked condition despite the presence of a potentially
      fatal complication. Between 1998 and 2001, 3 cases of otitic abscesses, including
      mastoid subperiosteal abscess, zygomatic abscess, and retropharyngeal abscess,
      were collected retrospectively. Their clinical presentation, results of
      investigations, and response to treatment were reviewed. After admission,
      intravenous antibiotics were prescribed and early surgeries were performed for
      eradication of infection source. The patients exhibited excellent postoperative
      recovery, without facial palsy, vertigo or other complications. To be a
      contemporary otologist, we should not overlook such severe complications of
      otologic diseases. Appropriate intravenous antibiotics and adequate surgeries, as
      soon as possible, are recommended. Advanced magnetic resonance imaging or
      computed tomographic scans of the temporal bone with wider windows are necessary.

PMID- 14703282
TI  - Tubulo-interstitial changes in glomerulopathy. II. Prognostic significance.
AB  - In the first part of this report mechanisms that lead to the development of
      tubulo-interstitial changes in glomerulonephritis (GLN) were presented. This
      issue is of a great practical importance, since explaining renal function in GLN
      solely by glomerular parameters yields to unreliable and inconsistent results.
      When the prognosis is based on the glomerular lesions only, the risk of
      progression to chronic renal failure is often underestimated. In routine biopsy
      material occurs that no glomerular sclerosis is seen, although the clinical signs
      of renal failure are present. On the other hand, one can see advanced glomerular
      lesions, which are not necessarily associated with deteriorated renal function
      when no interstitial fibrosis is noted. Although in the light of the published
      reports these facts are not surprising, they are often neglected in everyday
      nephropathological practice.

PMID- 14703283
TI  - A morphometric insight into glomerular and interstitial lesions in acutely
      rejected renal allografts.
AB  - Twenty-four renal allograft biopsy specimens from patients with acute renal
      transplant rejection (ARTR) for whom both light and electron microscopy as well
      as immunofluorescence microscopy and full clinical data were available were
      examined quantitatively. The specimens had similar histologic Banff 97 (IA and
      IB) scores. As a control 10 biopsy specimens of the kidneys removed because of
      trauma were used. Morphometric investigations were performed by means of a
      computer image analysis system to evaluate glomerular and interstitial lesions in
      ARTR. Another purpose of our study was to ascertain the possible relationships
      between alpha-smooth muscle actin (alpha-SMA) expression and selected
      morphometric parameters as well as monocyte/macrophage count. Our study revealed
      that the mean values of total glomerular cells per total glomerular area,
      mesangium (% of total glomerular area), glomerular and interstitial alpha-SMA
      staining, glomerular and interstitial monocytes/macrophages as well as
      interstitial volume were increased in ARTR in comparison with controls. In ARTR
      group significant positive correlations existed between glomerular expression of
      alpha-SMA and total glomerular cells per total glomerular area, as well as
      glomerular CD68+ cells. Moreover, interstitial expression of alpha-SMA and
      interstitial volume, as well as interstitial CD68+ cells were in ARTR patients
      also positively and significantly correlated. Similarly, in this group positive
      significant correlation between interstitial volume and interstitial CD 68+ cells
      was noted. In conclusion, our study suggests that glomerular hypercellularity and
      mesangial changes are common in ARTR, whereas enhanced interstitial fibrosis
      confirms a risk of early allograft injury in these cases.

PMID- 14703284
TI  - The comparison of the agreement in determining the histological grade of uterine
      endometrial endometrioid carcinoma, using the three-grade FIGO classification and
      the two-grade system.
AB  - The objective of the investigation was to compare the degree of interobserver
      agreement in determining the histological grade of uterine endometrial
      endometrioid adenocarcinoma using the criteria proposed by the three-grade FIGO
      classification (1988) and the new, two-grade system proposed by Lax et al.
      (2000). In the FIGO system, the assessment is focused on the amount of solid, non
      squamous growth pattern and the additional feature is the presence of the so
      called "notable nuclear atypia" (nuclear grade), with the latter criterion not
      having been precisely defined. In the two-grade system, the evaluation
      concentrates on the amount of the solid component, regardless of its character,
      type of neoplastic growth pattern (expansive or diffusely infiltrating) and the
      presence of necrosis within the tumor mass. A total of 133 cases of uterine
      endometrial carcinoma were evaluated, determining the stage according to the FIGO
      classification and assessing the histological grade based on the criteria
      presented by the above two systems. All the cases were separately examined by 5
      pathologists with varying degrees of experience in gynecological pathology. A
      higher degree of interobserver agreement was demonstrated when the two-grade
      system was employed as compared to the FIGO system, regardless whether the
      material was evaluated by experienced pathologists (FIGO k - 0.64 - 0.71, binary 
      0.91 - 0.92), or by individuals with little experience in gynecological
      pathology (FIGO k - 0.23 - 0.48, binary - 0.21 - 0.57). The data point to the
      superior character of the two-grade system as to the agreement of the
      histological grade assessment, but also suggest a considerable effect of
      experience on the precision of the evaluation.

PMID- 14703285
TI  - Benign clear-cell "sugar" tumor of the lung--a case report.
AB  - The authors present a rare case of a surgically treated so-called "sugar" tumor
      of the lung in a 68-year old male patient.

PMID- 14703286
TI  - Adenoma of the iris and ciliary body. Case report.
AB  - A case of rare tumor of the iris and ciliary body in a 24-year old woman is
      presented, which was diagnosed as adenoma of the nonpigmented ciliary body
      epithelium. The diagnosis was confirmed immunohistochemically.

PMID- 14703287
TI  - Telemedical management system of structured clinical documentation--application
      for quality assurance and multicenter clinical trials.
AB  - The paper presents telematic system designed for providing secure medical data
      communication through the Internet. Security is achieved by strong enctription.
      The data transmission between remote hospitals and center can be done in both
      directions. Transmitted data may be of different type especially HTML forms. The
      HTML forms filled in hospitals are automatically loaded to tables of relational
      database in the center. Generated in the system HTML forms meet structured
      clinical documentation needs. The telematic system was applied in project
      financed by government based on WHO standards for quality assurance system in
      obstetrics and neonatology. The system covers 40 hospitals and 13 regional health
      authorities for mother and child. 40 000 records concerning maternal, fetal and
      infant health status during pregnancy, delivery and pospartum period were stored.
      Collected data are used for developing indications for monitoring and evaluating
      perinatal health in Poland.

PMID- 14703288
TI  - Medical video server construction.
AB  - The paper discusses two implementation options for a Digital Video Library, a
      repository used for archiving, accessing, and browsing of video medical records.
      Two crucial issues to be decided on are a video compression format and a video
      streaming platform. The paper presents numerous decision factors that have to be
      taken into account. The compression formats being compared are DICOM as a format
      representative for medical applications, both MPEGs, and several new formats
      targeted for an IP networking. The comparison includes transmission rates
      supported, compression rates, and at least options for controlling a compression
      process. The second part of the paper presents the ISDN technique as a solution
      for provisioning of tele-consultation services between medical parties that are
      accessing resources uploaded to a digital video library. There are several
      backbone techniques (like corporate LANs/WANs, leased lines or even
      radio/satellite links) available, however, the availability of network resources
      for hospitals was the prevailing choice criterion pointing to ISDN solutions.
      Another way to provide access to the Digital Video Library is based on radio
      frequency domain solutions. The paper describes possibilities of both, wireless
      and cellular network's data transmission service to be used as a medical video
      server transport layer. For the cellular net-work based solution two
      communication techniques are used: Circuit Switched Data and Packet Switched
      Data.

PMID- 14703289
TI  - Project of an expert system supporting risk stratification and therapeutic
      decision making in acute coronary syndromes.
AB  - The aim of the project was to create a computer program--expert system, which
      will support a doctor when a management for patients with acute coronary syndrome
      needs to be chosen. The expert system consists of four modules: knowledge base,
      previous cases database, inference engine and explanation module. Knowledge base
      was created with support of clinical experts, based on current management
      standards, guidelines and results of clinical trials according to evidence-based
      medicine rules. Data from new patient are added to the case database. Inference
      engine integrates two types of reasoning rule-based and case-based reasoning.
      Computer expert system gives unambiguous and objective answer. Recommendation
      given by an expert system can be reliable. At present the system is tested in
      clinical practice. Strategies recommended by the system are compared to the
      management applied in patients treated in Cardiology Clinic.

PMID- 14703290
TI  - Security of medical data transfer and storage in Internet. Cryptography,
      antiviral security and electronic signature problems, which must be solved in
      nearest future in practical context.
AB  - The informatical revolution in computer age, which gives significant benefit in
      transfer of medical information requests to pay still more attention for aspect
      of network security. All known advantages of network technologies--first of all
      simplicity of copying, multiplication and sending information to many individuals
      can be also dangerous, if illegal, not permitted persons get access to medical
      data bases. Internet is assumed to be as especially "anarchic" medium, therefore
      in order to use it in professional work any security principles should be
      bewared. In our presentation we will try to find the optimal security solution in
      organisational and technological aspects for any medical network. In our opinion
      the harmonious co-operation between users, medical authorities and network
      administrators is core of the success.

PMID- 14703291
TI  - The Salomon advisory system supports a depressive episode therapy.
AB  - "Salomon" system is Polish computer advisory system for diagnostics of affective
      disorders. The system makes it possible to assess the relative intensity of
      depression measured by the depressive episode characteristic symptoms set based
      on scientific criteria for ICD-10 classification, M. Hamilton's depression rating
      scale and fuzzy logic. After two following consultations the system is able to
      generate the therapeutic index. The index depends on clinical situation. Basing
      on new computer technologies and ICD-10 classification the creation of the rank
      of the most effective therapeutic methods for the specific disorders is possible.
      Applying of neural network simulator makes it possible to find the similar
      depressive episode clinical subtype with its characteristic clinical picture used
      by clinician making a therapeutic decision.

PMID- 14703292
TI  - Telemedicine in the context of different medical specialities. The Polish
      perspective.
AB  - Two types of telemedicine are considered in the paper: pre-recorded and real
      time. The advantages and disadvantages of each type are described.The choice of
      telemedicine type depends on medical speciality. The separate branch of
      telemedicine--teleprevention of civilization diseases is discussed and examples
      of relevant WWW services in Poland are given. The own work examples of the Dept.
      of Medical Informatics, MUW, namely Onco-service of 200 protocols used in
      hematology and oncology and Cardio.net--a distributed teleinformation system for
      cardiology, are presented. IN CONCLUSION: the barriers of the development of
      telemedicine in Poland are caused by the organization of health service--Patients
      Funds using different software, no messaging standards and different
      reimbursement systems.

PMID- 14703293
TI  - Electronic patient record and archive of records in Cardio.net system for
      telecardiology.
AB  - In modern medicine the well structured patient data set, fast access to it and
      reporting capability become an important question. With the dynamic development
      of information technology (IT) such question is solved via building electronic
      patient record (EPR) archives. We then obtain fast access to patient data,
      diagnostic and treatment protocols etc. It results in more efficient, better and
      cheaper treatment. The aim of the work was to design a uniform Electronic Patient
      Record, implemented in cardio.net system for telecardiology allowing the co
      operation among regional hospitals and reference centers. It includes
      questionnaires for demographic data and questionnaires supporting doctor's work
      (initial diagnosis, final diagnosis, history and physical, ECG at the discharge,
      applied treatment, additional tests, drugs, daily and periodical reports). The
      browser is implemented in EPR archive to facilitate data retrieval. Several tools
      for creating EPR and EPR archive were used such as: XML, PHP, Java Script and
      MySQL. The separate question is the security of data on WWW server. The security
      is ensured via Security Socket Layer (SSL) protocols and other tools. EPR in
      Cardio.net system is a module enabling the co-work of many physicians and the
      communication among different medical centers.

PMID- 14703294
TI  - Oedipus and the oedipal.
AB  - Psychoanalysts have assumed that Sophocles can be seen through the lens of Freud,
      and that the Oedipus complex is about the incest taboo, guilt, and aggression.
      However, an examination of Sophocles' Oedipus Rex (as well as other plays)
      suggests that these themes are only a part of the central dynamics of the play,
      perhaps not the most central part. This article describes discrepancies between
      what Freud sees of oedipal dynamics and the oedipal dynamics at work in Sophocles
      and suggests possible explanations. A central theme of my discussion is the shame
      and blindness of Oedipus.

PMID- 14703295
TI  - "Abyss calls out to abyss": oedipal shame, invisibility, and broken identity.
AB  - The article derives from the experience of a double self or double reality. The
      abysses are often those of contradictory values and ideals, and with that
      opposite contents of shame or guilt, or the conflict between the sense of a deep
      inner hell that often is unspeakable and unnamable and that of a hollow and empty
      appearance. Absoluteness of judgment and its correlate, soulblindness toward the
      other, are the opposite to the empathy into the inner reality of the other.
      Soulblindness by the others creates massive shame in us. These dynamics are
      presented in a detailed case study.

PMID- 14703296
TI  - "Error that is anguish to its own nobleness": shame and tragedy in the Mill on
      the Floss.
AB  - In George Eliot's The Mill on the Floss, early unresolved emotional conflicts in
      Maggie set a pattern that leads her to "tragic error" as a young adult. Eliot
      links Maggie's dilemma with Sophocles's Ajax, in which the Greek hero takes his
      life after shame pushes him blindly to an action that results in only deeper
      humiliation and a shattering of his social being. In both works, emotional
      conflict is driven by a desire to transcend shame and ultimately leads to a
      mortifying error that is recognized only after the fact as tragic in its
      consequences.

PMID- 14703297
TI  - "Is there such a thing as happy shame?" He asked".
AB  - A man experienced shame for the first time during the termination phase of a 6
      year analysis. He asked: "Is there such a thing as happy shame?" The experience
      followed the transformation of a negative maternal transference into an
      affectionate one. However, in a moment of rage, he insulted the analyst and felt
      greatly ashamed. Yet, it was a "happy shame." This shame signaled the ability to
      tolerate painful oedipal failure and to integrate newly acquired self-evaluations
      into his sense of self in the presence of the analyst as a transferentially
      respectful and attentive maternal object.

PMID- 14703298
TI  - Oedipal shame, rejection, and adolescent development.
AB  - The definition of oedipal shame, dramatized in Sophocles' tragedy, is the painful
      affect resulting from accepting the reality of one's origins. A clinical example
      focusing on shame arising from adoption links oedipal shame to the theme of
      rejection. Furthermore, in adolescence the revival of the oedipal conflict may
      reactivate oedipal shame in which unconscious idealized fantasies of personal
      perfection and the object carried over from childhood have to be renegotiated.
      This process, illustrated by two clinical vignettes, may reveal entrenched
      masochistic defenses. An examination of a final scene from a film underscores the
      significance of oedipal shame in clinical practice.

PMID- 14703299
TI  - Shame conflicts as dream instigators: wish fulfillment and the ego ideal in dream
      dynamics.
AB  - Understanding of the instigatory dynamics of the dream is essential to the
      understanding of the dream as a fulfilled wish. Both the meaning and the function
      of the dream can be understood only in relation to the instigating disruption
      that drives the dream into being. It is the instigator of the dream that connects
      the working of the inner world with events in the external world. The literature
      on the process of dream instigation is scant, still deriving from Freud's
      metaphor of "capitalist and entrepreneur." Hidden shame conflicts that react to
      the dreamer's anticipation of danger of exposure and shame are significant
      factors in the instigation of the dream. Clinical material in support of this
      view is presented in the form of a verbatim session that included a dream.

PMID- 14703300
TI  - The "incompatible idea" revisited: the oft-invisible ego-ideal and shame
      dynamics.
AB  - The observation that incompatibility with conscience initiates deployment of
      defense goes back to Freud's conceptualization of the "incompatible idea" put
      forward in Studies on Hysteria. In this view, consciousness itself, insofar as it
      gives rise to painful affect resulting from conflict with the conscience, is the
      cornerstone for dynamic thinking, first as regards repression of traumatic memory
      and later for dynamic thinking generally. Subsequent discoveries about the
      conscience tended to give rise to pars pro toto thinking in which the new
      discovery replaced rather than added to the basic notion of conscience. Such pars
      pro toto imbalance exists in full force in psychoanalytic thinking today: Modern
      conflict theory privileges the postoedipal retaliative aspect of the conscience,
      as Kleinian thinking does for the preoedipal projective aspects of retaliation.
      Neither conceptualizes shame adequately. Kohut appreciated the role of shame, but
      discarded the notion of incompatibility with the ego-ideal. The incompatible idea
      model still provides an all-inclusive model for conceptualizing the conscience in
      the context of intrapsychic conflict.

PMID- 14703301
TI  - Hearing voices: the fate of the analyst's identifications.

PMID- 14703302
TI  - How race is lived in the consulting room.

PMID- 14703303
TI  - Effects of vitamin C on high blood pressure induced by salt in spontaneously
      hypertensive rats.
AB  - By breeding and feeding salt to spontaneously hypertensive rats (SHR)
      continuously over a long period (until 60 wk old), rats with systolic blood
      pressures (SBP) of over 270 mmHg were prepared. It was studied whether or not
      supplying large amounts of vitamin C (200 mg/rat/d) over this period might bring
      any beneficial effect to blood pressure. Moreover, physico-chemical studies were
      performed to measure the components and enzymes in the blood and urine at 53 and
      60 wk-old, and biochemical studies on vitamin C were also carried out in this
      experiment. Male (14 rats: 7 wk-old, 100-105 g) and female (15 rats: 7 wk-old, 95
      100 g) SHR were divided into three groups and bred continuously for 53 wk. The A
      group rats were given salt (2.5 g/100 g of diet), the B group rats were given
      salt and vitamin C (500 mg/100 mL of drinking water), and the C group rats were
      controls. The results showed almost the same tendencies between male and female
      rats. The body weights of the SHR in groups A and B were slightly lower than
      group C. The amount of food intake in groups A and B was almost the same as group
      C. The amount of water intake was, in the order from highest to lowest, group A,
      B and C. The SBP of group A rats exhibited the highest value among the three
      groups. The SBP of group B rats given vitamin C simultaneously with the salt
      resulted in a low blood pressure level close to that of the controls (group C).
      Furthermore, the DBP (diastolic blood pressure) also reflected the
      antihypertensive effect of vitamin C as well. The heartbeat of the rats was
      highest in group A, and was comparable to the value in the rats receiving vitamin
      C simultaneously with salt. For the tests on occult blood and protein in the
      urine, group A rats showed strong positive reactions, whereas the group B and C
      rats had decreased results for both tests. The organ weights of the liver,
      stomach, spleen, adrenal gland and kidneys per 100 g rat body weight were not
      different among the three groups. The values for the bilirubin content, and the
      enzyme activities of ALT and AST in the blood showed to be the highest in the
      male rats of group A. The values from the group B rats decreased near to the
      normal value like the control group. Vitamin C was found to decrease the blood
      pressure in SHR, and also to work effectively to protect liver and kidney
      functions even under the condition of very high blood pressure, as high as 250
      mmHg.

PMID- 14703304
TI  - alpha-Tocopheryl succinate activates protein kinase C in cellular and cell-free
      systems.
AB  - The effect of alpha-tocopheryl succinate (TS) on protein kinase C (PKC) activity
      was examined. TS increased the auto-phosphorylation of PKC in vascular smooth
      muscle cells. Furthermore TS activated isolated PKC-like phorbol 12-myristate 13
      acetate (PMA), although it was required at a significantly higher concentration
      than PMA for PKC activation. Molecular superimposition of the TS on PMA by
      computation suggested that TS took an active binding conformation to the PKC-like
      PMA, but that the conformational population was about 1/1.000. Consequently, we
      conclude that TS interacts directly with PKC, and activates it by taking an
      active conformation like PMA.

PMID- 14703305
TI  - The whole structure of the human nonfunctional L-gulono-gamma-lactone oxidase
      gene--the gene responsible for scurvy--and the evolution of repetitive sequences
      thereon.
AB  - L-Gulono-gamma-lactone oxidase (GULO), which catalyzes the last step of ascorbic
      acid biosynthesis, is missing in humans. The whole structure of the human gene
      homologue for this enzyme was disclosed by a computer-assisted search. Only five
      exons, as compared to 12 exons constituting the functional rat GULO gene, remain
      in the human genome. A comparison of these exons with those of their functional
      counterparts in rat showed that there are two single nucleotide deletions, one
      triple nucleotide deletion, and one single nucleotide insertion in the human
      sequence. When compared in terms of codons, the human sequence has a deletion of
      a single amino acid, two stop codons, and two aberrant codons missing one
      nucleotide besides many amino acid substitutions. A comparison of the remaining
      human exon sequences with the corresponding sequences of the guinea pig
      nonfunctional GULO gene revealed that the same substitutions from rats to both
      species occurred at a large number of nucleotide positions. From analyses of the
      molecular evolution of Alu sequences in the human GULO gene homologue, it is
      thought that two Alu sequences were inserted in the vicinity of a presumed
      position of lost exon 11 during the same period as GULO lost its function. It is
      predicted that six LINE-1 sequences located in and near the gene homologue were
      inserted not during that period.

PMID- 14703306
TI  - Effect of dietary fat level and sesamin on the polyunsaturated fatty acid
      metabolism in rats.
AB  - In this study, we examined the effects of sesamin and vegetable oil on the
      concentrations of polyunsaturated fatty acid (PUFA) and lipids (triacylglycerol,
      free cholesterol, and phospholipid), and beta-oxidation enzyme activities in the
      rat liver. Rats were fed a diet containing 5% (low-fat diet) or 20% (high-fat
      diet) salad oil (rapeseed oil: soybean oil, 7:3) with or without sesamin (0.5%
      w/w) for 4 wk. As a result, the concentrations of linoleic acid (LA, n-6), alpha
      linolenic acid (ALA, n-3), and total PUFA in the liver increased significantly as
      the result of the high-fat diet. In the high-fat diet groups, sesamin
      administration decreased the concentrations of LA, ALA, and total PUFA to almost
      the same level as the low-fat diet group, while it increased the concentrations
      of dihomo-gamma-linolenic acid (DGLA, n-6) and arachidonic acid (AA, n-6). The
      activities of carnitine acyltransferase and acyl-CoA dehydrogenase in liver
      mitochondria were enhanced by the intake of the high-fat diet, and were further
      enhanced by the administration of sesamin. Peroxisomal acyl-CoA oxidase activity
      was also enhanced by sesamin, while it was not affected by the dietary fat level.
      These results suggest that sesamin suppressed the increase of hepatic PUFA
      concentration caused by feeding the high-fat diet through enhancing the enzyme
      activities of fatty acid beta-oxidation and PUFA metabolism from LA and ALA.

PMID- 14703307
TI  - A study of the antioxidative and antimutagenic effects of Houttuynia cordata
      Thunb. using an oxidized frying oil-fed model.
AB  - The aims of this study were to evaluate the antioxidative effect of a traditional
      Taiwanese vegetable, Houttuynia cordata Thunb. (H. cordata), by subjecting
      rodents to oxidized frying oil-induced oxidative stress, and to examine the
      antimutagenic effects of H. cordata using the Ames test. Forty-eight Sprague
      Dawley rats were fed a diet of 0, 2, or 5% H. cordata and 15% fresh oil or
      oxidized frying oil (OFO) for 28 d. Levels of polyphenol in the feces, plasma,
      and liver were determined. The LDL lag time, plasma total antioxidant status
      (TAS), and levels of thiobarbituric acid-reactive substances (TBARS) were used as
      antioxidative indices, and the protein carbonyl group was used as an oxidative
      index. The results showed that the polyphenol content decreased in the plasma and
      increased in the feces when administering OFO, and the apparent absorption of
      polyphenol also decreased. The polyphenol content in plasma increased when giving
      H. cordata. There was a higher polyphenol concentration in the water extracts of
      H. cordata than in the methanol extracts. The OFO-fed groups had higher plasma
      TBARS and hepatic protein carbonyl group concentrations and shorter LDL lag times
      than those of the control group. The total TAS was elevated and the LDL lag time
      was prolonged when fed with H. cordata. In addition, both water and methanol
      extracts of H. cordata had an antimutagenic effect on benzo(a)pyrene, aflatoxin
      B1. and OFO, and showed a dose-dependent response using the Ames test. The
      antimutagenic ability of water extracts was higher than that of the methanol
      extracts. In conclusion, the polyphenol in H. cordata is easily absorbed and
      metabolized by rodents. H. cordata showed both antioxidative and antimutagenic
      properties under OFO feeding-induced oxidative stress.

PMID- 14703308
TI  - Antioxidant and anti-cataract effects of Chlorella on rats with streptozotocin
      induced diabetes.
AB  - The antioxidant activities of Chlorella in vitro and in vivo were investigated.
      Chlorella showed a strong antioxidant effect compared to various vegetables in a
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. To evaluate the
      antioxidant and anti-cataract effects in vivo, a 7.3% Chlorella powder was fed to
      rats with streptozotocin-induced diabetes for 11 wk. At the end of the
      experiment, Chlorella had decreased the blood glycated hemoglobin (hemoglobin
      A1c) and serum cholesterol levels significantly, however, it had not affected the
      serum glucose concentration. The serum lipid peroxide value (TBARS value) in the
      rats fed Chlorella was lower than that of the control rats. In the liver and
      kidney, Chlorella also reduced chemiluminescent intensities. In addition, it
      delayed the development of lens opacities. The lens lipid peroxide content of the
      rats fed Chlorella was lower than that of the control rats, however the
      differences were not significant. These results indicate that Chlorella has
      antioxidant activity and may be beneficial for the prevention of diabetic
      complications such as cataracts.

PMID- 14703309
TI  - Inhibition of lipase activities by citrus pectin.
AB  - The oral administration of pectin to rats reduced and delayed the peak plasma
      triacylglycerol concentration. Pectin inhibited the hydrolysis of
      trioleoylglycerol emulsified with soybean phosphatidylcholine by pancreatic,
      carboxylester, and lingual lipases in a concentration-dependent manner. However,
      the effective concentration of pectin for lingual lipase was 100 times lower than
      that for pancreatic lipase. Pectin did not inhibit the tributyrin- and p
      nitrophenylbutyrate-hydrolyzing activities by pancreatic and carboxylester
      lipase. When low molecular weight pectin was assayed, pectin at a molecular
      weight of 90,000 (MW 90) most strongly inhibited three lipase activities. When
      the effect of pH on pectin inhibition was analyzed using pancreatic lipase,
      strong inhibition was observed at an acidic pH (below pH 7.0). In the assay
      system, the pancreatic lipase protein levels in the supernatant and fat layer
      were estimated by Western blotting with an anti-pancreatic lipase antibody.
      Pectin reduced the amount of pancreatic lipase protein in the fat layer in a
      concentration-dependent manner and concomitantly increased that in the
      supernatant. These results suggest that pectin may interact with emulsified
      substrates and inhibit the adsorption of lipase to the surface of substrate
      emulsion.

PMID- 14703310
TI  - Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha
      glucosidase activity and postprandial hyperglycemia.
AB  - It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the
      wild and is a source of natural antioxidants. We previously reported that a
      glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"
      dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D
      glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the
      dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase
      inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in
      rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted
      gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose
      concentration in the serosal compartment were inhibited in the presence of 0.5
      and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in
      serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in
      sucrose- and maltose-loaded mice was significantly suppressed at an early stage,
      within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop
      extracts, respectively. These findings suggest that hyssop extracts inhibited the
      digestion of complex carbohydrates, but not that of absorbable monosaccharide,
      and might be a useful supplemental food for hyperglycemia.

PMID- 14703311
TI  - Inorganic selenite supplementation and protection against hyperoxic injury in
      neonates.
AB  - This study was designed to determine if oral sodium selenite supplementation to
      Se-depleted rat pups furnishes protection against hyperoxic lung injury. Twelve
      female rats were bred and fed a Se-deficient (0.04 ppm Se) diet during pregnancy
      and lactation. Pups were supplemented either with 0 or 3.2 ng Se/g body weight
      daily from days 2 to 7. On day 4, two litters were mixed, with half of the pooled
      litter assigned to an air environment and the other half to an oxygen
      environment. Dams cross-fostered pups for 4 d. Selenite supplementation increased
      pup plasma and liver selenium concentration and the liver activity of glutathione
      peroxidase (GPx). However, lung GPx activity was more affected by oxygen exposure
      than selenite supplementation. While oral Se supplementation of the pups showed a
      tendency for decreased incidence of lung injury with oxygen exposure, this
      apparent effect was not statistically significant. Selenium-supplemented pups
      also showed a trend toward larger internal surface area and lung volume than
      selenium-depleted pups. These data indicate that early postnatal selenium
      repletion via direct oral selenite supplementation may be beneficial to rat pups
      against hyperoxic lung injury.

PMID- 14703312
TI  - DNA-based identification of Brassica vegetable species for the juice industry.
AB  - Since kale (Brassica oleracea var. acephala), a cruciferous vegetable with a high
      level of vitamins and functional compounds beneficial to health and wellness, has
      become widely used in the juice industry, a precise method for quality control of
      vegetable species is necessary. We describe here a DNA-based identification
      method to distinguish kale from cabbage (Brassica oleracea var. capitata), a
      closely related species, which can be inadvertently mixed with kale during the
      manufacturing process. Using genomic DNA from these vegetables and combinatory
      sets of nucleotide primers, we screened for random amplified polymorphic DNA
      (RAPD) fragments and found three cabbage-specific fragments. These RAPD
      fragments, with lengths of 1.4, 0.5, and 1.5 kb, were purified, subcloned, and
      sequenced. Based on sequence-tagged sites (STS), we designed sets of primers to
      detect cabbage-specific identification (CAI) DNA markers. Utilizing the CAI
      markers, we successfully distinguished more than 10 different local cabbage
      accessions from 20 kale accessions, and identified kale juices experimentally
      spiked with different amounts of cabbage.

PMID- 14703313
TI  - Political interference in American science: why Europe should be concerned about
      the actions of the Bush administration.

PMID- 14703314
TI  - Reasons to seek medical attention for a skin check-up: the layman's perspective.
AB  - BACKGROUND: The incidence of cutaneous malignant melanoma has increased rapidly
      in Sweden during the last 20 years. One way of reducing mortality is through
      early diagnosis. The aim of this study was to explore the reasons why different
      people seek medical attention for pigmented skin lesions, using a qualitative
      approach. METHODS: Three groups of laymen (N=90), all with varying experience of
      pigmented skin lesions, were interviewed. RESULTS: Most of the respondents had
      sought medical attention primarily because they were worried about a specific
      skin lesion. Patients with melanoma mentioned concern about very dark skin
      lesions more often than other respondents did. Encouragement by family and
      friends was also important. CONCLUSION: Very dark coloration in pigmented skin
      lesions might be added to public recommendations for early discovery of melanoma.
      No other new nonmedical feature or circumstance was identified when the results
      were compared with two established systems for clinical diagnosis of melanoma
      (the ABCD criteria and the seven-point checklist).

PMID- 14703315
TI  - Predictors of work satisfaction among physicians.
AB  - BACKGROUND: Work satisfaction among physicians is an important concern because it
      is associated with several important aspects of care, such as the continuity of
      care and health care costs. In this study, a brief work satisfaction
      questionnaire was developed, its validity was assessed, and it was used to
      examine the determinants of work-related satisfaction among a sample of Swiss
      physicians. METHODS: Based on the literature, a 17-item work satisfaction
      questionnaire was developed that addressed five dimensions of satisfaction:
      patient care, work-related burden, income-prestige, personal rewards and
      professional relations with colleagues. This questionnaire was administered by
      mail to 1904 doctors practising in Geneva, Switzerland; 1184 (59%) responded.
      Additional data were collected on physicians' personal and work situation.
      RESULTS: In general, physicians were more satisfied with the following aspects of
      their current work situation: patient care, professional relations and personal
      rewards (intellectual stimulation, opportunities for continuing medical
      education, enjoyment at work). The lowest satisfaction scores were found for work
      related burden (workload, time available for family, friends or leisure, work
      related stress, administrative burden) and work-related income and prestige. In
      multivariate models, variables associated with most dimensions of satisfaction
      included type of practice (physician in training were less satisfied), specialty
      (internal medicine specialists and pediatricians were more satisfied), time spent
      on administrative tasks (globally negative effect), time spent on continuing
      medical education (globally positive effect). Age and sex had only a minor
      influence on satisfaction scores. CONCLUSION: Physician work satisfaction is
      multidimensional and can easily be measured using a short self-administered
      questionnaire. This instrument could be useful to monitor changes in the near
      future.

PMID- 14703316
TI  - Increasing prevalence of overweight, obesity and physical inactivity: two
      population-based studies 1986 and 1994.
AB  - INTRODUCTION: The aim of this study was to investigate the 1986-1994 trend in
      obesity, overweight and sedentary leisure-time physical activity status, and the
      educational gradient in overweight and obesity in the city of Malmo, Sweden.
      MATERIAL/METHODS: The public health surveys in Malmo 1986 and 1994 are cross
      sectional studies. A total of 4,800 and 5,600 individuals aged 20-80 years were
      randomly chosen to be interviewed by a postal questionnaire. The participation
      rates were 74% and 71%. Obesity was defined as BMI 30.0 or more and overweight as
      BMI 25.0-29.9. The prevalences of leisure-time physical inactivity, obesity and
      overweight were computed, and the differences between 1986 and 1994 as well as
      educational gradients in overweight and obesity were assessed. RESULTS: The
      prevalence of obesity increased from 4.6% to 11.4% (p<0.001) among men and from
      6.1% to 9.8% (p<0.001) among women. The prevalence of overweight (BMI 25.0-29.9)
      increased from 33.9% to 45.2% (p<0.001) among men, and from 19.6% to 29.1%
      (p<0.001) among women. The prevalence of leisure time physical inactivity
      increased among men from 14.7% to 18.1% (p<0.001) among men and from 19.4% to
      26.7% (p<0.001) among women. The increasing prevalences of obesity, overweight
      and physical inactivity were observed in all age, country of origin and
      educational status groups. The educational differences in BMI 25.0+ observed
      among both men and women in 1986 disappeared among men in 1994. In contrast,
      educational differences in obesity (BMI 30.0+), not seen in 1986, appeared in
      1994 among men. CONCLUSION: The proportions of the population with obesity and
      overweight increased significantly between 1986 and 1994 for both men and women.
      The increasing prevalence of physical inactivity seems to be an important
      explanation.

PMID- 14703317
TI  - Health measures: differentiating associations with gender and socio-economic
      status.
AB  - BACKGROUND: In a cohort survey on health-related lifestyles, four different
      measures of health were analysed with regard to their associations with gender,
      socio-economic and psychosocial factors. METHODS: The survey was carried out in
      Berne, Switzerland. Response rate was 64% in the initial interview and 83% in the
      second interview, from which the data presented were derived, resulting in 923
      participants aged 56 to 66 years. Along with socio-economic and psychosocial
      parameters, four self-report health measures were obtained, namely self-rated
      health, physical fitness, number of medical conditions and restrictions caused by
      medical conditions. Regression analysis was used to investigate and compare their
      associations with gender, socio-economic and psychosocial factors and relevant
      interaction terms. RESULTS: Gender was statistically significantly associated
      with physical fitness, number of medical conditions and subsequent restrictions.
      Education and income showed statistically significant associations with self
      rated health and fitness. Psychological factors were statistically significantly
      associated with all health measures. Gender showed to interact with education,
      income interacted with internal health locus of control. Analyses with separated
      genders showed that the association of socio-economic status with self-rated
      health and fitness was statistically significant in women only. CONCLUSION: The
      different health measures showed considerable variation in strengths of
      association with health-related factors, most noticeably so with gender and socio
      economic status. The choice of health measures in population studies should
      comply with the intention to analyse its associations with any of those related
      factors, or, in reverse, with the wish to prevent their confounding properties.

PMID- 14703318
TI  - Utilization of prenatal care in poorer and wealthier urban neighbourhoods in
      Turkey.
AB  - BACKGROUND: The objectives of this study are to identify the individual- and
      neighbourhood-level determinants of utilization of prenatal care, and to identify
      self-reported reasons for not receiving prenatal care in Turkey. METHODS: A
      household-based cluster sample of 1249 women who had a child less than two years
      old were interviewed in five Turkish cities. Multilevel regression analysis was
      run to predict the influences of individual- and neighbourhood-level
      characteristics on utilization of prenatal care. RESULTS: Utilization of prenatal
      care and the quality of the care received were found to be significantly lower in
      poorer neighbourhoods. Using multilevel regression analysis (two levels),
      educational level, income, parity and having health insurance were found to be
      individual-level determinants, while quality of care offered and stability of the
      local population were found to be neighbourhood-level determinants of utilization
      of prenatal care. The most frequent self-reported reason for receiving no
      prenatal care was 'not having any complaint', and the second was 'insufficient
      financial resources'. CONCLUSION: There was a big difference between poor and
      wealthy neighbourhoods in utilization of prenatal care. This difference was
      partly due to a contextual effect of neighbourhood status; but mostly due to
      individual-level variables. Improving the quality of prenatal care may increase
      not only the benefits of prenatal care, but also its utilization, especially in
      the public sector. Health and social policies have to take into account diversity
      among individuals and neighbourhoods in the course of efforts to improve service
      quality.

PMID- 14703319
TI  - Social gradients in years of potential life lost in Ireland.
AB  - BACKGROUND: The study of mortality differentials by class or socio-economic group
      is underdeveloped in Ireland in comparison to other countries. The work that has
      been done has used a standardized mortality ratio (SMR) methodology to measure
      deaths. There has been no previous work exploring the social gradient in years of
      potential life lost (YPLL) in Ireland. METHODS: The aim is to investigate socio
      economic mortality differentials for men aged between 15 and 69 in Ireland, using
      YPLL as a measure of premature mortality. The design is a mortality trends study.
      The study is based on mortality data supplied by the Central Statistics Office in
      Ireland and population data taken from the Census for the years 1981 and 1991.
      The data covers all male deaths aged 15-69 in the years 1981 and 1991. Social
      position is measured by a 12-category socio-economic group (SEG) framework and by
      a more aggregate four-category occupational classification system. RESULTS: When
      age at death is taken into account through YPLL, injury and poisoning is a major
      cause of premature mortality in Ireland for all socio-economic groups. The
      results also show significant differentials in YPLL by 12-category SEG in
      Ireland. There was a widening of the social gap during the period 1981 to 1991 as
      measured by the YPLL ratio between lower manual/upper non-manual occupational
      groups. The use of YPLL as a measure of premature mortality highlights the
      importance of respiratory disease and injury and poisoning as the major sources
      of health inequality in 1981 and 1991. CONCLUSIONS: YPLL is an important
      indicator of general mortality and for monitoring mortality differentials by
      socio-economic group. Current health inequalities as measured by YPLL are
      unacceptably high in Ireland. A comprehensive government strategy to reduce
      inequalities in mortality is required, having the primary objective of improving
      the economic and social circumstances of people in the lower manual occupational
      category. There is also a need to develop measurable priorities and programmes
      for the reduction of premature mortality in the injury and poisoning category for
      all social groups, and especially for people in the lower manual group. This
      means action now to prevent future deaths from road accidents, accidents at work
      and suicides.

PMID- 14703320
TI  - Unusually strong association between education and mortality in young adults in a
      community with a high rate of injection-drug users.
AB  - BACKGROUND: To examine the association between education and mortality for
      various causes of death in young adults in a community with a high rate of
      injection-drug users. METHODS: Linked mortality study based on mortality records
      for 1996 and 1997 and on 1996 population census data from the Region of Madrid
      (Spain). The association between educational level and mortality was estimated by
      the mortality rate ratio. RESULTS: After adjustment for age and other
      socioeconomic variables the mortality rate in men and women aged 25-44 years with
      no education was, respectively, 4.7 and 3.7 times higher than in men and women
      with the highest educational level. The causes of death with the strongest
      association were chronic liver disease and cirrhosis, AIDS and diseases of the
      heart in both sexes and suicide in men. For these causes of death the mortality
      rate ratio between persons with the lowest and highest educational level ranged
      from 6.8 to 21.8 in men and from 4.1 to 16.9 in women. CONCLUSIONS: These causes
      of death are the leading specific causes of death in persons aged 25-44 years.
      Given that probably a substantial part of deaths from diseases of the heart in
      this age category are drug-related, the common denominator of the excess
      mortality related poor education seems to be drug injection.

PMID- 14703321
TI  - Deprivation and systematic stroke prevention in general practice: an audit among
      general practitioners in the Rotterdam region, The Netherlands.
AB  - BACKGROUND: To investigate differences in quality of preventive care provided by
      general practitioners (GPs) to patients at risk of stroke living in deprived and
      non-deprived neighbourhoods in the Rotterdam region. METHODS: A 'deprivation
      score' was used to categorize neighbourhoods according to their deprivation
      status. Data on the process of patient care were collected by means of chart
      review and interviews with GPs. Cases of stroke (n=188) were retrospectively
      audited by an expert panel with guideline-based review criteria. To measure
      differences in quality of patient care between neighbourhoods, deprivation scores
      were related to scores for sub-optimal care. RESULTS: After adjustment for socio
      demographic characteristics, patients in deprived neighbourhoods had an increased
      risk (OR 1.95 (95% CI: 0.98-3.90)) of having received sub-optimal preventive care
      if compared with patients in non-deprived neighbourhoods. This excess risk was
      limited to women (OR 3.57 (95% CI: 1.39-9.16) vs OR 1.01 (95% CI: 0.41-2.48) in
      men). Adjustment for socio-demographic characteristics and risk factor
      distribution did not change the OR for women to receive sub-optimal care
      significantly (OR 3.21 (95% CI: 1.24-8.31)). Sub-optimal care originated mainly
      from deficiencies in follow-up of treated hypertensive and diabetes patients and
      evaluation of patients' cardiovascular risk profile. Among treated hypertensive
      women in deprived neighbourhoods who received sub-optimal care, the mean number
      of deficiencies related to follow-up was almost double that of the corresponding
      group in non-deprived neighbourhoods. CONCLUSION: Quality of care to prevent
      stroke in general practice differs considerably between deprived and non-deprived
      neighbourhoods. Patients in deprived neighbourhoods, and women in particular,
      have almost twice the risk of receiving sub-optimal preventive care.

PMID- 14703322
TI  - Limited effect of highly active antiretroviral therapy among HIV-positive
      injecting drug users on the population level.
AB  - There is evidence that HIV-positive injecting drug users benefit less than other
      risk groups from highly active antiretroviral therapy that has been available
      since 1996. In this multicentre European study the impact of the availability of
      highly active antiretroviral therapy on the progression rates to AIDS and death
      among injecting drug users with a documented date of HIV seroconversion is
      studied. After highly active antiretroviral therapy became available the risk of
      AIDS and death for injecting drug users decreased by 28% and 36%, which is less
      than has been reported for other risk groups.

PMID- 14703323
TI  - HIV risk behaviour of older persons.
AB  - BACKGROUND: This study investigated social and psychological determinants of
      preventive behaviour in HIV-relevant situations. METHODS: Using computer-assisted
      telephone survey methodology, 2275 male and female were interviewed about their
      sexual habits. RESULTS: For the first time in Switzerland, data concerning HIV
      relevant protection as well as their determinants were systematically collected
      also from persons older than 45. This age group (n=834) showed an increased risk
      with regard to HIV-relevant sexual contacts. CONCLUSIONS: The present findings
      call for more adequate monitoring of sexual behaviour of people older than 40 and
      suggest the development and implementation of respective age-specific prevention
      measures.

PMID- 14703324
TI  - Detecting psychosocial problems among 5-6-year-old children in preventive Child
      Health Care: the validity of a short questionnaire used in an assessment
      procedure for detecting psychosocial problems among children.
AB  - BACKGROUND: An extended re-assessment of the psychometric properties of the
      LSPPK, an instrument aimed at identifying children with emotional and behavioural
      problems. METHODS: Data came from a national sample in The Netherlands of parents
      of 1248 children (aged 5-6 years) interviewed by child health professionals
      (CHP). Data were obtained regarding psychosocial problems, treatment status and
      scores on the LSPPK (Parent and CHP Index), and on the Child Behavior Checklist
      (CBCL). The scale structure, reliability, criterion and content validity and
      added value of the LSPPK were assessed using the CBCL and treatment status as
      criteria. RESULTS: The scale structure corresponded with that found originally;
      the LSPPK improved the prediction of problems according to the CBCL, compared to
      predictions using readily available risk indicators alone. Reliability varied
      between 0.55 and 0.69. For the LSPPK Parent Index, sensitivity varied between
      0.42 and 0.50. For the CHP Index sensitivity varied between 0.60 and 0.96, but
      specificity varied between 0.76 and 0.79. Both indices were very sensitive for
      attention and social problems, but less so for other problems. CONCLUSION: The
      LSPPK Parent Index cannot distinguish sufficiently between children with or
      without serious problems. Either too many children with problems remain unnoticed
      or too many children without problems are labelled as a case. The LSPPK CHP
      Index, reflecting the CHP's interpretation of the Parent Index after interviewing
      the parents does not compensate adequately for the weaknesses of the Parent
      Index. Better assessment procedures and strategies need to be developed.

PMID- 14703325
TI  - The NorVold Abuse Questionnaire (NorAQ): validation of new measures of emotional,
      physical, and sexual abuse, and abuse in the health care system among women.
AB  - BACKGROUND: In the literature about abuse, large variations in prevalence rates
      exist. Validated research instruments are scarce and are needed urgently. Our aim
      was to validate the 13 questions concerning the experiences of abuse among women
      in the NorVold Abuse Questionnaire against an interview and two validated
      questionnaires. METHOD: Data collection was in two parts. i) The NorVold Abuse
      Questionnaire was sent to a random sample of 2000 women in Ostergotland. ii) A
      subsample of 64 women was interviewed, and filled in the Conflict Tactic Scale,
      the Sexual Abuse Questionnaire, and the NorVold Abuse Questionnaire for a second
      time. The interview had open questions about abuse and was considered our gold
      standard. RESULTS: The response rate was 61%. The abuse variables in The NorVold
      Abuse Questionnaire showed good test-retest reliability (84-95%). Specificity was
      98% for all kinds of abuse except physical (85%). Sensitivity ranged from 75%
      (emotional) to 96% (physical). The likelihood ratio ranged from 38 to 43 for all
      kinds of abuse except physical (likelihood ratio 6). NorAQ performed better
      against the interview than against the Sexual Abuse Questionnaire and equally
      against the Conflict Tactic Scale. High lifetime prevalence rates of abuse were
      found: emotional 21.4%; physical 36.4%; sexual 16.9%; abuse in the health care
      15.6%. Prevalence rates of abuse dropped considerably when a criterion of current
      suffering was added. CONCLUSIONS: The abuse variables in NorAQ have good
      reliability and validity.

PMID- 14703326
TI  - Drug distribution and expenditure: the issue of epoetin in Italy.

PMID- 14703327
TI  - Monitoring musculoskeletal complaints.

PMID- 14703328
TI  - Hand-wrist and cervical vertebral maturation indicators: how can these events be
      used to time Class II treatments?
AB  - BACKGROUND: Ossification events in the hand and wrist and in the cervical
      vertebrae have been shown to occur at specific times before, during and after the
      adolescent growth spurt, but there is still debate about the applicability of
      these findings to the clinical management of Class II cases. The aim of this
      study was to relate, on an individual basis, cervical vertebral maturation stages
      and hand-wrist ossification events to the timing of peak statural and mandibular
      growth in a group of indigenous Australians. METHODS: Velocity curves for stature
      and mandibular growth were constructed for 47 boys and 27 girls, and maturation
      events were then plotted on the curves. RESULTS: For the majority of children,
      peak velocity in mandibular growth coincided with peak velocity in stature.
      Particular combinations of hand-wrist and cervical maturation events occurred
      consistently before, during or after the adolescent growth spurt. CONCLUSION: Our
      findings are consistent with those for North American children and we believe
      that assessment by orthodontists of a combination of hand-wrist and cervical
      vertebral maturation stages will enhance prediction of the adolescent growth
      spurt, thereby contributing to a positive, purposeful and more confident approach
      to the management of Class II cases.

PMID- 14703329
TI  - A longitudinal index study of orthodontic stability and relapse.
AB  - BACKGROUND: Previous studies of stability and relapse after orthodontic treatment
      report short-term stability is generally followed by slow relapse to the original
      condition. What these studies do not report is whether this relapse is continuous
      or interspersed with periods of improvement or stability. METHODS: A subjective 0
      10 index of malocclusion was used to record post-treatment stability and relapse
      over 10 to 12 years following fixed appliance orthodontic treatment of 24
      patients. The severity scores were plotted on timelines. RESULTS: Episodes of
      change, both favourable and unfavourable, were interspersed with episodes of
      stability. CONCLUSIONS: Changes in the first 3 and 12 months post-treatment are
      indicative of the 10 to 12 years post-treatment outcomes. This index may provide
      a useful instrument to analyze patients and/or their study models longitudinally.

PMID- 14703330
TI  - Stability of combined Le Fort I maxillary advancement and mandibular reduction.
AB  - BACKGROUND: There have been reports that correction of severe Class III
      abnormality by single jaw surgery may invite relapse in the long-term. The
      purpose of this study was to retrospectively evaluate the stability of combined
      Le Fort I maxillary advancement and bilateral sagittal split osteotomies for
      mandibular reduction. METHODS: Thirty patients with a skeletal Class III
      malocclusion underwent bimaxillary surgery using rigid fixation and
      interpositional bone grafting of the maxilla. The average age was 24.4 years, and
      the mean follow-up period was 20 months (Range: 12-63 months). Post-operative
      changes were measured on lateral cephalometric radiographs using an anatomical
      best-fit technique. RESULTS: The maxilla was advanced, on average, 6.1 mm (SD:
      1.8 mm) and repositioned superiorly at PNS 1.9 mm (SD: 2.1 mm). The mandible was
      repositioned posteriorly 5.6 mm ISD: 4.2 mm) at menton, which also auto-rotated
      superiorly. At follow-up, the maxilla relapsed horizontally 0.6 mm (SD: 1.1 mm, p
      < 0.01) with no significant vertical change. The maxillary central incisors were
      proclined and the interincisal angle was reduced. Menton relapsed anteriorly 1.4
      mm (SD: 2.7 mm, p < 0.01), and gonion rotated superiorly 1.5 mm (SD: 2.3 mm, p <
      0.001). In 67 per cent of cases menton moved anteriorly less than 2.5 mm. The
      overjet and overbite did not change significantly. CONCLUSIONS: The data show
      that 12-months post-operatively, maxillary advancement combined with mandibular
      setback was relatively stable in the horizontal and vertical planes.

PMID- 14703331
TI  - Comparison of radiation levels from computed tomography and conventional dental
      radiographs.
AB  - BACKGROUND: With the increasing use of computed tomography (CT) in oral diagnosis
      and treatment planning, concern has been expressed about the high levels of
      radiation used, and the associated risks. OBJECTIVES: The purpose of this study
      was to compare the radiation doses of facial CT scans with the radiation doses
      taking a lateral cephalometric radiograph, a panoramic radiograph (OPG), an
      occlusal film, and an intra-oral periapical radiograph. METHODS: An Alderson
      Rando anthropomorphic phantom head was used for the analysis. Thirty-six lithium
      fluoride thermoluminescent dosimeters were placed in the phantom head in
      locations representing radiosensitive sites. Standard facial CT scans and
      conventional radiographs (lateral cephalometric, OPG, maxillary occlusal, intra
      oral periapical) were then taken of the phantom head. RESULTS: The following
      radiation doses were measured: maxillo-mandibular CT scan, 2.1 mSv; maxillary CT
      scan, 1.40 mSv; mandibular CT scan, 1.32 mSv; lateral cephalometric radiograph,
      0.005 mSv; OPG, 0.010 mSv; maxillary occlusal, 0.007 mSv; intra-oral periapical
      radiograph, 0.005 mSv. CONCLUSIONS: CT scans produce significantly more ionising
      radiation than conventional radiographs. This factor should be taken into account
      when considering a CT scan as an alternative to a survey with conventional
      radiographs. While CT scans offer many advantages over conventional radiography
      the high radiation dose to patients, and the cost of this procedure should be
      considered.

PMID- 14703332
TI  - Distribution of the epithelial rests of Malassez and their relationship to blood
      vessels of the periodontal ligament during rat tooth development.
AB  - BACKGROUND: There is some evidence that the epithelial cell rests of Malassez
      partition the root surface from the periodontal ligament blood vessels, and may
      protect the root from resorption. OBJECTIVE: The aim of the present study was to
      determine the distributions of the epithelial rests of Malassez (ERM) and blood
      vessels in the periodontal ligament (PDL) of the developing rat first molar
      before, during and after emergence. METHODS: Four Sprague-Dawley rats were
      sacrificed at two days, one week, two weeks, three weeks, four weeks and six
      weeks of age. After processing, the maxillae were embedded in paraffin, and
      sectioned longitudinally and transversely. The sections were stained with a
      double immuno-histochemical technique which utilised a keratin antibody AE1-AE3
      (1:2,000) and an endothelial antibody Factor VIII (1:10,000) to enable
      simultaneous labelling of ERM and blood vessels. ERM and blood vessel counts were
      obtained from the mesio-buccal roots of three week, four week and six week-old
      rats, whilst qualitative observations were made for the earlier developmental
      stages. RESULTS: ERM cells and cell clusters were found in the tooth third of the
      PDL width at the three, four and six week stages. Cells and cell clusters
      increased in number with age, especially in the upper third of the mesio-buccal
      root. The largest numbers of cells and clusters were found on the distal surfaces
      of the roots in all age groups. Cells and clusters in all root surfaces increased
      from three to four weeks, but decreased from four to six weeks. The greatest
      number of blood vessels was found in the bone-side third of the PDL. The distal
      surface had the highest proportion of blood vessels, and the palatal surface the
      least proportion. The number of blood vessels in all surface quadrants did not
      vary much from three to four weeks of age, but increased from four to six weeks
      of age, possibly as a reaction to tooth emergence and occlusal function.
      Physiological root resorption was only observed after tooth emergence, and
      appeared to be related to loss of continuity of the ERM network and the incursion
      of blood vessels. CONCLUSIONS: Orthodontic root resorption can be regarded as an
      exaggerated response to loss of PDL homeostatic control, possibly mediated by the
      epithelial rests of Malassez.

PMID- 14703333
TI  - Extraction treatment using a palatal implant for anchorage.
AB  - AIM: To describe the use of Straumann Orthosystem implants for orthodontic
      anchorage. METHODS: The Straumann Orthosystem consists of a titanium palatal
      implant and connected device, which can be used when absolute anchorage is
      required. In the present study the implant was placed in the midline at the
      junction of the alveolar process and hard palate. The implant was osseointegrated
      13 weeks after placement. A palatal arch attached to the implant and upper first
      molar bands was used to provide stationary anchorage in a 23 year-old female with
      protruding upper anterior teeth and moderate crowding of both arches. CONCLUSION:
      A palatal implant provides stationary anchorage for retraction of anterior
      maxillary teeth.

PMID- 14703334
TI  - Root resorption during orthodontic treatment.

PMID- 14703335
TI  - A brief history of the Australian Society of Orthodontists. The first fifty
      years: 1927 to 1977.

PMID- 14703336
TI  - A new synthesis of lysergic acid.
AB  - [reaction: see text] (+/-)-Lysergic acid has been synthesized via an economical 8
      step route from 4-bromoindole and isocinchomeronic acid without the need to
      protect the indole during the synthesis. Initial efforts to form the simpler 3
      acylindole derivatives first and then cyclize these were unsuccessful in the
      cyclization step.

PMID- 14703337
TI  - Palladium-catalyzed carbonylation of haloindoles: no need for protecting groups.
AB  - [reaction: see text] For the first time, palladium-catalyzed carbonylations of
      unprotected bromoindoles have been performed successfully with different N- and O
      nucleophiles. Various indole carboxylic acid derivatives are accessible in
      excellent yield. For example, aminocarbonylation of 4-, 5-, 6-, or 7-bromoindole
      with arylethylpiperazines provides a direct one-step synthesis for CNS active
      amphetamine derivatives.

PMID- 14703338
TI  - Stoichiometric and catalytic deuterium and tritium labeling of "unactivated"
      organic substrates with cationic Ir(III) complexes.
AB  - [reaction: see text] Ir(III) complex [Cp(PMe(3))IrMe(CH(2)Cl(2))][BAr(f)] (1) was
      used to introduce deuterium stoichiometrically into substituted
      naphthalene/benzene templates and several "drug-like" entities. The exchange
      process is tolerant of a wide array of functional groups. Labeling of warfarin
      using subatmospheric pressures of T(2) led to specific activities and total
      activities rivaling current functional group directed tritium labeling methods.
      When paired with the appropriate deuterium donor, Cp(PMe(3))Ir(H(3))OTf (4) was
      found to deuterate a number of organic compounds catalytically.

PMID- 14703339
TI  - Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O
      protected trans-3,5-bis(hydroxymethyl)morpholines.
AB  - [reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS,
      (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert
      butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)
      symmetric class of chiral reagents, were prepared with excellent optical purity.
      A key step in the synthesis is the coupling of a serinol derivative with 2,3-O
      isopropylideneglycerol triflate or its equivalent. This methodology was extended
      to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert
      butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building
      block.

PMID- 14703340
TI  - Highly functionalized organolithium reagents for enantiomerically pure alpha
      amino acid synthesis.
AB  - [reaction: see text] Highly functionalized l-serine-derived organolithium
      reagents have been generated and reacted with a variety of electrophiles,
      delivering novel enantiomerically pure adducts. These adducts were then converted
      into homochiral amino alcohols and novel nonproteinogenic alpha-amino acids,
      including an aspartic acid mimic that has been synthesized in an enantiomerically
      pure form for the first time.

PMID- 14703341
TI  - Highly selective asymmetric acetate aldol reactions of an N-acetyl
      thiazolidinethione reagent.
AB  - [reaction: see text] A highly diastereoselective acetate aldol reaction that uses
      a tert-leucine-derived thiazolidinethione auxiliary and dichlorophenylborane has
      been developed. The reaction proceeds in excellent yields and with high
      diastereoselectivities (drs range from 9.5:1 to >100:1).

PMID- 14703342
TI  - Copper-mediated synthesis of N-acyl vinylogous carbamic acids and derivatives:
      synthesis of the antibiotic CJ-15,801.
AB  - [reaction: see text] Copper(I)-mediated C-N bond formation has been employed to
      prepare both N-acyl vinylogous carbamic acids and ureas. The novel N-acyl
      vinylogous carbamic acid antibiotic, CJ-15,801, was synthesized using this
      methodology.

PMID- 14703343
TI  - Facile synthesis, aggregation behavior, and cholesterol solubilization ability of
      avicholic acid.
AB  - [reaction: see text] Avicholic acid, a major constituent of the bile of several
      avian species, was synthesized in eight steps from readily available
      chenodeoxycholic acid in 9% overall yield using Breslow's remote
      functionalization strategy in a key step. Micelle formation and equilibrium
      cholesterol solubilization properties were studied for avicholate in aqueous
      solution.

PMID- 14703344
TI  - Arylation of heterocycles via rhodium-catalyzed C-H bond functionalization.
AB  - [reaction: see text] A new method for the rhodium-catalyzed arylation of a
      variety of heterocycles has been developed. The reaction provided moderate to
      good yields of the arylated products. A preliminary mechanistic investigation of
      this reaction revealed the intermediacy of an isolable N-heterocyclic carbene
      complex.

PMID- 14703345
TI  - Highly substituted pyrrolidinones and pyridones by 4-CR/2-CR sequence.
AB  - [reaction: see text] By combining a Ugi four-component reaction of isocyanides,
      phosphonoacetic acids, primary amines, and glyoxals or alternatively 3-keto
      aldehydes with a subsequent Wittig ring-closing reaction (using the
      Horner/Wadsworth/Emmons variant (HWE)), highly substituted 5-oxo-2,5-dihydro-1H
      pyrrole-2-carboxylic acid amides and 6-oxo-1,2,3,6-tetrahydro-pyridine-2
      carboxylic acid amides can be assembled, respectively. The corresponding tandem
      of a Passerini reaction on 3-keto aldehydes and subsequent Wittig ring closure
      does not afford the expected six-membered 6-oxo-3,6-dihydro-2H-pyran-2-carboxylic
      acid amides but instead leads to the formation of 4-oxo-pent-2-enoic acid amides
      via an elimination route.

PMID- 14703346
TI  - Expanded chemistry of formamidine ureas.
AB  - [reaction: see text] Formamidine ureas display a rich manifold of reactivity.
      Thiols induce substitution at the carbonyl carbon to give thiolcarbamates; base
      mediated alkylation and acylation occurs at the terminal urea nitrogen, and a new
      fragmentation/acylation pathway has been uncovered with isocyanates.

PMID- 14703347
TI  - Enhanced two-photon absorption with novel octupolar propeller-shaped fluorophores
      derived from triphenylamine.
AB  - [structure: see text] Novel octupolar fluorophores derived from the symmetrical
      functionalization of a triphenylamine core with strong acceptor peripheral groups
      via phenylene-ethynylene linkers have been synthesized and shown to exhibit high
      fluorescence quantum yields, very large TPA cross-sections in the red-NIR region,
      and suitable photostability.

PMID- 14703348
TI  - Synthesis and stability of oligonucleotides containing acyclic achiral nucleoside
      analogues with two base moieties.
AB  - [structure: see text] Nucleotide building blocks with two base moieties were
      synthesized and incorporated into oligonucleotides. One of the two bases is
      involved in base pairing within the double helix, while the other base is
      sticking out of the minor groove. This system may be used for presenting sequence
      information at the outside of the helix.

PMID- 14703349
TI  - Total synthesis of herbimycin A.
AB  - [structure: see text] Herbimycin A (HA) belongs to a class of antibiotics known
      as the benzoquinoid ansamycins. Members of this class have shown promising
      biological activity as Hsp90 inhibitors. An enantioselective synthesis of HA is
      described, employing asymmetric syn-crotylation methodology to introduce the C10,
      C11, C14, and C15 stereocenters. The C6-C7 stereocenters were introduced using
      Brown's alpha-pinene-derived gamma-methoxy allylborane reagent. The C12
      stereocenter was established by diastereoselective hydroboration.

PMID- 14703350
TI  - (Salen)Mn-catalyzed epoxidation of alkenes: a two-zone process with different
      spin-state channels as suggested by DFT study.
AB  - [structure: see text] A novel (two-zone process with different spin-state
      channels) mechanistic picture for the Jacobsen-Katsuki reaction is presented that
      provides insight into the still elusive understanding of the epoxidation
      mechanism. For the first time, we show that the salen moiety of the catalyst can
      be explicitly involved in the epoxidation process.

PMID- 14703351
TI  - Peptide quinoline conjugates: a new class of RNA-binding molecules.
AB  - [reaction: see text] A synthesis of 4,8-disubstituted 2-phenylquinoline amino
      acids is reported with the incorporation of one example into a peptide by solid
      phase synthesis. The phenylquinoline-containing peptide binds an RNA target with
      nanomolar affinity (K(D) = 208 nM). The strategy can be used to prepare a variety
      of 2-substituted quinoline amino acids for alteration of affinity in intercalator
      peptides. Since quinolones represent an important class of antibacterials, these
      compounds may be useful in the discovery of new antibacterial agents.

PMID- 14703352
TI  - Selective oxidation of zirconocyclopentenes via organoboranes.
AB  - [reaction: see text] A new, convenient, one-pot protocol is described for
      oxidation of zirconocyclopent-2-enes selectively at the sp(3) carbon by efficient
      transfer to electrophilic ((c)Hex)(2)BCl followed by oxidation with H(2)O(2)/NaOH
      to afford 1-alkylidene-2-hydroxymethylcyclopentanes. Results with several
      substrates show that overall reaction efficiencies for the zirconocene-mediated
      enyne cyclization, boron transmetalation, and oxidation sequence are generally
      comparable to yields obtained from protonation of intermediate zirconocycles. The
      formation of E/Z olefin isomers from the cyclization-oxidation sequence and an
      acid-catalyzed pinacol-type rearrangement of a vinylsilane are described.

PMID- 14703353
TI  - Toward the total synthesis of natural peloruside a: stereoselective synthesis of
      the backbone of the core.
AB  - [reaction: see text] An asymmetric synthesis of the backbone of the core of
      natural peloruside A is described. Key elements include reiterative application
      of enantioselective allylation to establish the stereochemistry of the backbone
      and a double asymmetric aldol reaction to successfully couple two fragments.

PMID- 14703354
TI  - Spiculoic acids A and B, new polyketides isolated from the Caribbean marine
      sponge Plakortis angulospiculatus.
AB  - [structure: see text] Two novel polyketides, spiculoic acids A (1) and B (2),
      have been isolated from extracts of the Caribbean marine sponge
      Plakortisangulospiculatus. The structures of 1 and 2 were elucidated by detailed
      analysis of spectroscopic data. Spiculoic acid A (1) showed in vitro cytotoxicity
      against human breast cancer MCF-7 cells. It has a putative polyketide biogenetic
      origin that involves incorporation of four butyrate units and a Diels Alderase
      catalyzed intramolecular [4 + 2] cycloaddition reaction.

PMID- 14703355
TI  - A general synthesis of substituted indoles from cyclic enol ethers and enol
      lactones.
AB  - [reaction: see text] X = CH2, C[double bond]O, R2 = H, alkyl. A general method
      was developed for the one-pot synthesis of highly functionalized indoles from
      simple, commercially available aryl hydrazines and cyclic enol ethers. Enol
      lactones were also used as substrates, affording substituted indole acetic acid
      or indole propionic acid derivatives. This procedure affords 2,3-disubstituted
      indoles as single regioisomers from the appropriately substituted enol ether or
      enol lactone. This method was highlighted in the efficient synthesis of the
      antimigraine drug sumitriptan and the antiinflammatory drug indomethacin.

PMID- 14703356
TI  - Squaric acids: a new motif for designing inhibitors of protein tyrosine
      phosphatases.
AB  - [structure: see text] Protein tyrosine phosphatases (PTPases) are important
      targets in medicinal chemistry. These enzymes play a role in a number of human
      diseases, including type II diabetes and infection by Yersinia pestis, the
      causative agent of bubonic plague. Derivatives of squaric acids such as 2-aryl-1
      hydroxycyclobut-1-ene-3,4-diones represent a new class of monoanionic inhibitors
      for PTPases.

PMID- 14703357
TI  - First diastereoselective chiral synthesis of (-)-securinine.
AB  - [reaction: see text] A diastereoselective total synthesis of securinine in
      optically pure form was achieved by employing ring-closing metathesis of the
      corresponding dienyne compound as a key step.

PMID- 14703358
TI  - Oxidative cyclization of beta-hydroxyenones with palladium(II): a novel entry to
      2,3-dihydro-4H-pyran-4-ones.
AB  - [reaction: see text] A palladium(II)-mediated oxidative cyclization was found to
      be effective for the preparation of structurally diverse 2,3-dihydro-4H-pyran-4
      ones from the corresponding beta-hydroxyenones. Attractive features of this
      transformation include the ready availability of the starting enones, the
      regiocontrol, and the easy access of enantiopure 2,3-dihydro-4H-pyran-4-one from
      the corresponding enantiopure enone.

PMID- 14703359
TI  - Palladium-catalyzed Suzuki-Miyaura cross-couplings of sulfonyl chlorides and
      boronic acids.
AB  - [reaction: see text] R = tolyl, phenyl, 4-halophenyl, 1-naphthyl, 2-nitrophenyl,
      benzyl, methallyl, r1 = aryl, heteroaryl, alkenyl. Arene-, arylmethane, and alk-2
      ene-1-sulfonyl chlorides undergo Suzuki-Miyaura cross-coupling with arene-,
      heteroarene-, and alkeneboronic acids in THF at reflux. The reactivity order is
      ArI > ArSO(2)Cl > ArBr >> ArCl.

PMID- 14703360
TI  - Facile O-arylation of phenols and carboxylic acids.
AB  - [reaction: see text] A facile, transition-metal-free O-arylation procedure for
      phenols and aromatic carboxylic acids has been developed that affords good to
      excellent yields of arylated products under very mild reaction conditions. A
      methoxy-substituted aryl triflate affords O-arylated products in high yields with
      excellent regioselectivity. This chemistry tolerates a variety of functional
      groups.

PMID- 14703361
TI  - Enantioselective preparation of the C1-C11 fragment of apoptolidin.
AB  - [reaction: see text] A novel approach toward the synthesis of the triene portion
      of the biologically active polyketide apoptolidin is described. The use of an
      iterative thionyl chloride rearrangement/oxidation sequence to construct
      trisubstituted olefins is explored.

PMID- 14703362
TI  - Direct copper(I) iodide dimethyl sulfide catalyzed conjugate addition of alkenyl
      groups from vinylzirconocene reagents.
AB  - [reaction: see text] CuI.0.75DMS complex is an excellent catalyst for the direct
      conjugate addition of alkenyl groups from vinylzirconocene reagents to alpha,beta
      unsaturated aldehydes and ketones. The presence of the catalyst with an
      alkenylzirconocene, at +40 degrees C in THF, circumvents the need for making
      discrete alkenylcopper reagents. The catalyst is superior in terms of product
      yields and alkene flexibility in comparison to other copper(I) sources as well as
      the nickel(II)-catalyzed conjugate addition. This simple one-pot procedure shows
      that only 1 equiv of the vinylzirconocene is needed.

PMID- 14703363
TI  - Nucleophilic displacement at benzhydryl centers: asymmetric synthesis of 1,1
      diarylalkyl derivatives.
AB  - [reaction: see text] Activation of substituted 1,1-diarylmethanols as their
      corresponding toluenesulfonates and subsequent displacement with a range of
      carbon, nitrogen, oxygen, and sulfur nucleophiles proceeds in 81-96% yield.
      Enantiomerically enriched diarylmethanols 8a-c were activated and displaced with
      pyridine acetate enolate with complete stereochemical inversion at carbon to
      yield 1,1-diarylalkyl derivatives 10a-c without loss of optical purity.

PMID- 14703364
TI  - Synthesis of polysubstituted 4,5,6,7-tetrahydrofuro[2,3-c]pyridines by a novel
      multicomponent reaction.
AB  - [reaction: see text] A novel three-component synthesis of tetrahydrofuro[2,3
      c]pyridines from readily accessible starting materials is described. Simply
      heating a toluene solution of an aminopentynoate, an aldehyde, and an alpha
      isocyanoacetamide in the presence of ammonium chloride provided the 4,5,6,7
      tetrahydrofuro[2,3-c]pyridines in good to excellent yield. The fused ring system
      is produced in this one-pot process by the concomitant formation of five chemical
      bonds.

PMID- 14703365
TI  - Conversion of D-glucals into L-glycals and mirror-image carbohydrates.
AB  - [reaction: see text] L-Glycals can be prepared in seven steps from readily
      available D-glucals, enabling the facile construction of mirror-image
      carbohydrates such as the L-lactosamine derivative shown above.

PMID- 14703366
TI  - Stereoselective aldol-type cyclization reaction mediated by dibutylboron
      triflate/diisopropylethylamine.
AB  - [reaction: see text] Dibutylboron triflate/diisopropylethylamine mediated aldol
      type cyclization provides an expedient route for the stereoselective synthesis of
      cyclic ethers in a single step. The method is highly efficient for the
      stereoselective synthesis of 4-cis-tetrahydropyranones. The reaction is proposed
      to proceed via an S(N)1-type mechanism through a chair-like transition state, in
      which both substituents occupy equatorial positions.

PMID- 14703367
TI  - Efficient one-step aldol-type reaction of ketones with acetals and ketals
      mediated by dibutylboron triflate/diisopropylethyl amine.
AB  - one-step Mukaiyama aldol type reaction [reaction: see text] A highly efficient
      one-step Mukaiyama aldol-type reaction has been developed for the synthesis of
      beta-alkoxy carbonyl compounds starting from ketones and acetals/ketals. The
      reaction is mediated by a combination of Bu(2)BOTf and i-Pr(2)NEt affording the
      products in high yields. Formation of the two possible diastereoisomers of the
      beta-alkoxy ketones from the chiral acetals shows that the condensation takes
      place by an S(N)1 mechanism, involving prior opening of the acetal to an oxonium
      ion.

PMID- 14703368
TI  - Catalytic asymmetric carbohydroxylation of alkenes by a tandem diboration/Suzuki
      cross-coupling/oxidation reaction.
AB  - [reaction: see text] Chiral nonsymmetric 1,2-diboron adducts are generated by
      catalytic enantioselective diboration. Oxidation of these adducts provides 1,2
      diols in good yield. Alternatively, 1,2-diboron compounds may be reacted, in
      situ, with aryl halides wherein the less hindered C-B bond participates in cross
      coupling. The remaining C-B bond is then oxidized in the reaction workup thereby
      allowing for net asymmetric carbohydroxylation of alkenes in a tandem one-pot
      diboration/Suzuki coupling/oxidation sequence.

PMID- 14703369
TI  - Synthesis of enantiopure 2-C-methyl-D-erythritol 4-phosphate and 2,4
      cyclodiphosphate from D-arabitol.
AB  - [reaction: see text] Two key intermediates of the newly discovered mevalonate
      independent pathway for isoprenoid biosynthesis were prepared. Optically pure 2-C
      methyl-D-erythritol 4-phosphate and 2,4-cyclodiphosphate were chemically
      synthesized from D-arabitol using a convenient benzylidene and tert
      butyldimethylsilyl protection of polyhydroxylated intermediates. The new scheme
      offers a straightforward route to analogues and labeled forms.

PMID- 14703370
TI  - Three-component homo 3 + 2 dipolar cycloaddition. A diversity-oriented synthesis
      of tetrahydro-1,2-oxazines and FR900482 skeletal congeners.
AB  - [reaction: see text] The reaction of nitrones, formed in situ by reaction of
      hydroxylamines with aldehydes, with 1,1-cyclopropanediesters results in the
      formation of tetrahydro-1,2-oxazines via a homo 3 + 2 dipolar cycloaddition. This
      three-component coupling allows for the formation of a diverse array of
      cycloadducts with excellent diastereoselectivity (>95%) and yields (66-96%). The
      procedure has been used in the two-step preparation of congeners of the FR900482
      skeleton.

PMID- 14703372
TI  - Perspective on fluorocarbon chemistry.
AB  - Fluorocarbons, organic molecules with carbon skeletons and fluorine "skins",
      differ fundamentally from their hydrocarbon counterparts in interesting and
      useful ways. A selection of the myriad applications fluorocarbons and their
      derivatives have found in modern life is described and related to molecular
      properties. Salient aspects of the nature and reactivity of fluorocarbon
      compounds are highlighted by comparison with their more familiar hydrocarbon
      analogues.

PMID- 14703373
TI  - Assessing the substrate selectivities and enantioselectivities of eight novel
      Baeyer-Villiger monooxygenases toward alkyl-substituted cyclohexanones.
AB  - Genes encoding eight Baeyer-Villiger monooxygenases have recently been cloned
      from bacteria inhabiting a wastewater treatment plant. We have carried out a
      systematic investigation in which each newly cloned enzyme, as well as the
      cyclohexanone monooxygenase from Acinetobacter sp. NCIB 9871, was used to oxidize
      15 different alkyl-substituted cyclohexanones. The panel of substrates included
      equal numbers of 2-, 3-, and 4-alkyl-substituted compounds to probe each enzyme's
      stereoselectivity toward a homologous series of synthetically important
      compounds. For all 4-alkyl-substituted cyclohexanones tested, enzymes were
      discovered that afforded each of the corresponding (S)-lactones in >/=98% ee.
      This was also true for the 2-alkyl-substituted cyclohexanones examined. The
      situation was more complex for 3-akyl-substituted cyclohexanones. In a few cases,
      single Baeyer-Villiger monooxygenases possessed both high regio- and
      enantioselectivities toward these compounds. More commonly, however, they showed
      only one type of selectivity. Nonetheless, enzymes with such properties might be
      useful as parts of a two-step bioprocess where an initial kinetic resolution is
      followed by a regioselective oxidation on the isolated, optically pure ketone.

PMID- 14703374
TI  - Conformation of the galactose ring adopted in solution and in crystalline form as
      determined by experimental and DFT 1H NMR and single-crystal X-ray analysis.
AB  - The solution-state conformations of various galactose derivatives were determined
      by comparison of the experimental (1)H-(1)H vicinal coupling constants to those
      calculated using density functional theory (DFT) at the B3LYP/cc-pVTZ//B3LYP/6
      31G(d,p) level of theory. The agreement between the experimental and calculated
      vicinal coupling constants for 1,2:3,4-di-O-isopropylidene-alpha-d
      galactopyranose was good, thereby confirming an (O)S(2) skew conformation for it
      and its derivatives on the basis of their similar observed couplings. Single
      crystal X-ray analysis of 1,2:3,4-di-O-isopropylidene-6-O-(3,4,6-tri-O-acetyl-2
      deoxy-2-N-phthalimido-beta-d-glucopyranosyl)-alpha-d-galactopyranose and
      1,2,3,4,6-penta-O-acetyl-alpha-d-galactopyranose provided (O)S(2) and (4)C(1)
      conformations, respectively, for the galactose ring in the solid state. The solid
      state structures proved to be suitable starting structures for further DFT
      structure refinement or for immediate calculation of the coupling constants.

PMID- 14703375
TI  - Conformational flexibility of Corey lactone derivatives indicated by absorption
      and vibrational circular dichroism spectra.
AB  - Infrared absorption and vibrational circular dichroism (VCD) spectra of four
      Corey lactone derivatives (diol, benzoate, p-phenylbenzoate, and bisbenzoate)
      were measured and analyzed on the basis of ab initio computations. The analysis
      interpreted most of the spectral features as well as the differences among
      individual compounds. Despite the common rigid lactone residue, conformational
      behaviors and spectral features of the derivatives were found to be different,
      because of hydrogen bonding and solvent effects. Recognition of common molecular
      parts in the spectra of different molecules increases the potential of using VCD
      for monitoring the purity of intermediates in chiral syntheses. For the
      derivatives, a conserved spectral component corresponding to the lactone skeleton
      could be identified on the basis of theoretical analysis but was relatively weak
      in intensity.

PMID- 14703376
TI  - An approach toward azacycles using photochemical and radical cyclizations of N
      alkenyl substituted 5-thioxopyrrolidin-2-ones.
AB  - The photochemical reactions of a series of cyclic N-alkenyl-substituted
      thioimides have been examined. Irradiation of N-3-methylbut-3-enyl-5-thioxo
      pyrrolidin-2-one (16) results in intramolecular [2 + 2] cycloaddition to give the
      highly strained thietane 17, whose structure was confirmed on the basis of its X
      ray analysis. Treatment of cycloadduct 17 with dimethyl(methylthio)sulfonium
      tetrafluoroborate gave 2,5,6,7-tetrahydropyrrolizin-3-one (20) in good yield.
      Further reduction of 20 with Raney-Ni afforded 5,5-dimethylhexahydro-pyrrolizin-1
      one (21). This sequence of reactions demonstrates the facility with which the 2 +
      2 photoadduct can be converted into the pyrrolizidine alkaloid core skeleton. The
      photochemistry of the closely related N-butenyl thioxopyrrolidin-one (22)
      proceeded in a slightly different fashion and produced 7-mercaptomethyl
      tetrahydropyrrolizin-3-one (24) in 68% yield. In contrast to the above results,
      irradiation of the thioxaphthalimido system containing an N-cycloalkenyl group in
      the side chain gave rise to products derived by gamma-hydrogen abstraction from
      the n-pi triplet excited state. The photobehavior of the related N-3-alkenyl
      pyrrolidine-2,5-dithione system (62) was also studied and found to give products
      derived from both a 2 + 2 cycloaddition (63) and hydrogen atom transfer (64).
      Finally, the reaction of several N-alkenyl substituted thioimides (71-73) with
      tributylstannane in the presence of AIBN gave cyclized products derived from
      transient radical intermediates.

PMID- 14703377
TI  - Synthesis and self-assembly of supramolecular dendritic "Bow-Ties": effect of
      peripheral functionality on association constants.
AB  - Self-assembled polyester dendritic bow-ties with various peripheral groups were
      prepared, and their association constants were measured by (1)H NMR in CDCl(3).
      The two complementary dendrons were prepared by attachment of either a
      bis(adamantylurea) or a glycinylurea to the focal point of the dendron. The
      parent self-assembled system with benzylidene acetals on one periphery and
      isopropylidene acetals on the other had an association constant of 520 M(-)(1).
      Upon deprotection of one dendron, the association constant is increased by more
      than an order of magnitude as the solubility of the hydroxyl-terminated dendron
      in CDCl(3) is decreased. In contrast, attachment of tri(ethylene oxide) units to
      the periphery of one dendron lowers the association constant by almost an order
      of magnitude. The causes of these relatively large changes in complex strength
      are discussed in terms of solubility, steric effects, competitive hydrogen
      bonding, and the structure of the dendritic scaffold.

PMID- 14703378
TI  - 3-Hydroxy-4-oxo-3,4-dihydro-5-azabenzo-1,2,3-triazene.
AB  - The known but long-neglected compound HODhat was shown to be in certain
      situations a useful peptide coupling additive. Uronium and phosphonium salts with
      HODhat built into the system were also useful stand-alone coupling reagents.
      Comparisons with related additives and coupling reagents showed that the new
      systems were sometimes more and sometimes less effective than previously
      described systems in the case of stepwise and segment couplings. Applications to
      assembly of the model decapeptide ACP showed that HDATU was far more effective
      than HDTU and more effective than HATU under some conditions.

PMID- 14703379
TI  - Organophosphorus and nitro-substituted sulfonate esters of 1-hydroxy-7
      azabenzotriazole as highly efficient fast-acting peptide coupling reagents.
AB  - Organophosphorus esters 9, 10, 14, and 15 prepared via reaction of diethyl- and
      diphenylphosphoryl chloride, di(o-tolyl)phosphinyl chloride, and 2,8
      dimethylphenoxaphosphinyl chloride with HOAt are excellent coupling reagents for
      peptide synthesis which are generally superior to their uronium/guanidinium
      analogues and HOBt- or HODhbt-derived phosphate ester counterparts in minimizing
      loss of configuration during segment coupling. The phosphinyl analogues are more
      shelf-stable than the phosphoryl systems. The new reagents have been tested in
      segment couplings leading to two tripeptides (20, 21) and a hexapeptide 22.
      Outstanding utility is also shown for the solid-phase assembly of the ACP
      decapeptide. Similar results were obtained with the 2- and 4-nitro- and 2,4
      dinitrophenylsulfonyl esters derived from HOAt.

PMID- 14703380
TI  - Sulfur extrusion with tin radical: synthesis of 4',5'-didehydro-5'-deoxy-5'
      (tributylstannyl)adenosine, an intermediate for potential inhibitors against S
      adenosyl homocysteine hydrolase.
AB  - A new approach has been developed for the synthesis of potential inhibitors of S
      adenosyl-l-homocysteine (AdoHcy) hydrolase. The key intermediate 9-[2,3-bis-O
      (tert-butyldimethylsilyl)-5-(Z)-(tributylstannyl)-5-deoxy-beta-d-erythro-pent-4
      enofuranosyl]adenine (12) was prepared by sulfur extrusion reaction of 4',5'
      didehydro-5'-deoxy-5'-(phenylthio)adenosine (11) with tributyltin radical. It was
      found that this reaction proceeds stereoselectively, forming 12 irrespective of
      the geometry of 11. Compound 12 readily underwent iodination, bromination, and
      chlorination with retention of configuration, whereas fluorination gave both (Z)-
      and (E)-isomers of vinyl fluoride. Because of the susceptibility of 12 to
      protodestannylation, the (Z)-vinyl iodide (13), prepared in quantitative yield
      from 12, was used as a substrate for C-C bond formation. Various types of carbon
      substituents (phenyl, vinyl, trifluorovinyl, ethynyl, and cyano) were introduced
      to the 5'-position of the 5-deoxy-beta-d-erythro-pent-4-enofuranosyl structure to
      open up a new route to potential inhibitors of AdoHcy hydrolase.

PMID- 14703381
TI  - Total synthesis of (+/-)-alantrypinone by hetero Diels-Alder reaction.
AB  - An efficient total synthesis of (+/-)-alantrypinone 4 by hetero Diels-Alder
      reaction of a novel pyrazine diene 9 with either a functionalized 3
      alkylideneoxindole or 3-methyleneoxindole itself is described. The Diels-Alder
      reactions provide both the desired regiochemistry and exo selectivity. An
      interesting anionic equilibration between alantrypinone 4 and its epimer 31 or
      between its ester analogues 23 and 24 has been demonstrated, and a mechanism has
      been proposed.

PMID- 14703382
TI  - Experimental and theoretical studies of the dimerizations of imidoylketenes.
AB  - Reaction conditions are presented that, for the first time, allow the generation
      and dimerization of N-alkylimidoylketenes, e.g.,1d, while avoiding the
      intramolecular rearrangements observed under conventional conditions. The dimer
      of 1d (22a) is the result of [4 + 2] cycloaddition across the C=C bond of one
      ketene. In contrast, the N-H imidoylketene 1c dimerizes across the C=O bond to
      form 24b. Furthermore, N-methylbenzoimidoylketene (5b), in equilibrium with the
      more stable benzoazetidinone 14b, gives the formal [4 + 4] dimer 8b. B3LYP/6
      31G(d) transition structure calculations on these three modes of dimerization
      reproduce and offer explanations for these divergent regiochemistries. Both [4 +
      2] dimerizations have planar, pseudopericyclic transition structures (25a and
      29b). Five transition structures were found for the formation of 8b. A unique
      pseudopericyclic dimerization of 5b with an orthogonal [4 + 4] geometry (31) has
      a barrier of only 0.7 kcal/mol. However, the overall lowest energy pathway
      involves concerted addition of 5b across a sigma bond in 14b via 35.

PMID- 14703383
TI  - A "classical" tetrahydroxycalix[4]arene adopting the 1,2-alternate conformation.
AB  - The first example of a "classical" tetrahydroxycalixarene, which adopts the 1,2
      alternate conformation both in solution and in the crystal, is described.
      Calixarene derivatives with two distal methylene groups substituted in a trans
      fashion by phenyl (5a) or mesityl (5b) groups were synthesized via addition of
      PhMgBr/CuCN or MesMgBr/CuCN to the bis(spirodiene) derivative 3. Whereas the
      phenyl-substituted calixarene derivative 5a adopts the usual "cone" conformation,
      solution NMR data and X-ray crystallography indicate that the more crowded
      mesityl derivative 5b adopts a 1,2-alternate conformation with the two mesityl
      groups located at isoclinal positions of the macrocycle.

PMID- 14703384
TI  - Macromolecular polyradicals with cyclic triphosphazene as a core. Spectral and
      electrochemical properties.
AB  - Stable cyclotriphosphazenes 5 and 6, with three and four carbon radical centers,
      have been prepared by condensation of (4-hydroxy-2,6-dichlorophenyl)bis(2,4,6
      trichlorophenyl)methyl radical (4) with tetrachloro-2,2'
      dioxybiphenylcyclotriphosphazene (7). EPR studies of both polyradicals in fluid
      solution suggest an electronic communication through the PN multiple bonds of the
      cycle. EPR spectral results in frozen solutions and magnetic susceptibility
      measurements in the solid are consistent with very weak electron-electron dipolar
      interactions. Reductive cyclic voltammetry shows a single three-electron redox
      couple for triradical 5 and a single four-electron redox couple for tetraradical
      6. Both polyradicals 5 and 6 have been chemically oxidized to a stable trication
      5(3+) and a tetracation 6(4+), respectively, by electron-transfer reactions.

PMID- 14703385
TI  - Syntheses and reactions of optically active alpha-aminoallenylstannanes.
AB  - Lithiation/stannylation of optically active N-propargyloxazolidinones produced
      optically active alpha-oxazolidinonylallenylstannanes. Reaction of these with
      aldehydes in the presence of BF(3).OEt(2) produced beta-hydroxypropargylamines
      with high syn diastereoselectivity and ee. These were converted to gamma-hydroxy
      beta-amino acids by oxidative cleavage of the alkyne.

PMID- 14703386
TI  - Total synthesis of pancratistatin relying on the [3,3]-sigmatropic rearrangement.
AB  - A new total synthesis of the antitumor alkaloid, pancratistatin (1), has been
      accomplished from readily available starting materials. Claisen rearrangement of
      the racemic dihydropyranethylene 17 was employed to construct the A and C rings
      with the appropriate stereochemistry. In addition, the Ireland-Claisen
      rearrangement of the enantiomerically pure 9 followed by ring-closing metathesis
      provided the important intermediate 24, thus implying that our approach could
      yield the enantioselective synthesis of (+)-pancratistatin. With the
      appropriately functionalized cyclohexene 24, stereo- and regiocontrolled
      functional group interchanges, such as iodolactonization, dihydroxylations, and a
      cyclic sulfate elimination reaction, facilitated the production of the target
      natural product.

PMID- 14703387
TI  - A versatile stereoselective synthesis of endo,exo-furofuranones: application to
      the enantioselective synthesis of furofuran lignans.
AB  - A new stereoselective route to endo,exo-2,6-diarylfurofuranones has been
      developed using Mn(III)-mediated intramolecular cyclopropanation and C-H
      insertion reactions as key C-C bond-forming steps. Mn(III)-mediated oxidative
      cyclization of acetoacetate derivative 11 afforded 1-acetyl-4-aryl-3
      oxabicyclo[3.1.0]hexan-2-one (12) with excellent diastereocontrol (d.r. 22:1).
      Subsequent Lewis acid-catalyzed opening of the activated cyclopropane ring
      present in 12 with benzylic alcohols then gave alpha-acetyl-gamma-butyrolactones
      16 and 18-20, which reacted efficiently with in situ-generated TfN(3) to secure
      the key alpha-diazo-gamma-butyrolactones 22-25. Highly stereoselective rhodium
      catalyzed C-H insertion reactions of diazolactones 22-25 completed the synthesis
      of endo,exo-2,6-diarylfurofuranones 26-29 in overall yields ranging from 41 to
      48% from 1-phenylallyl alcohol (+/-)-10. The approach developed for the
      furofuranones 26-29 was then applied to the asymmetric syntheses of four
      furofuran lignans, (+)-xanthoxylol (1), (+)-methylxanthoxylol (2), (+)
      epipinoresinol (3), and (+)-epieudesmin (4), starting from enantiomerically
      enriched 1-arylallyl alcohol (S)-31.

PMID- 14703388
TI  - Synthesis of enantiopure 4-hydroxypipecolate and 4-hydroxylysine derivatives from
      a common 4,6-dioxopiperidinecarboxylate precursor.
AB  - tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared
      in good yield starting from Boc-Asp-O(t)Bu and other beta-amino acids. By analogy
      with chiral tetramic acids, their reduction by NaBH(4) in CH(2)Cl(2)/AcOH
      afforded the corresponding cis-4-hydroxy delta-lactams in good yield and
      stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of
      6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still
      obtained as the major product but the de values were consistently lower. 4
      Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp
      O(t)Bu (three steps, 63% overall yield), has proven to be an excellent building
      block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and
      36% overall yield, respectively) and for the synthesis of a protected 4
      hydroxylysine derivative 29 (41% overall yield).

PMID- 14703389
TI  - Self-protection: the advantage of radical oligomeric mixtures in organic
      synthesis.
AB  - Atom-transfer radical oligomers of allyl iodoacetates were converted to 4
      pentenoic acids upon treatment with zinc. Reactions of the radical oligomers of
      various omega-alkenyl iodoacetates with Grignard reagents afforded the
      corresponding substituted tetrahydrofuran derivatives. These results indicated
      that radical oligomeric mixtures not only serve as versatile intermediates in
      organic synthesis, but also exhibit unique advantages in that the oligomeric
      mixtures are self-protected and the deoligomerization functions as the
      simultaneous deprotection.

PMID- 14703390
TI  - Highly enantioselective Friedel-Crafts reaction of aromatic amines with ethyl
      glyoxylate catalyzed by chiral titanium(IV) complexes: practical synthesis of
      aminomandelic acid derivatives.
AB  - The asymmetric Friedel-Crafts reaction of a variety of N,N-dialkylanilines with
      ethyl glyoxylate has been achieved by the catalysis of titanium complexes of
      BINOL derivatives to give corresponding ethyl esters of p-N,N
      dialkylaminomandelic acids in high yields (85-99%) and good to excellent
      enantioselectivities (80-96.6% ee) under the optimized reaction conditions, which
      has added a new catalyst for this class of reactions. The reaction could also be
      carried out at a reduced catalyst loading (1 mol %) in gram scale, which provided
      a practical synthesis of enantiopure aminomandelic acid derivatives.

PMID- 14703391
TI  - A DFT investigation of the addition reaction of monomeric lithium enolate derived
      from propiophenone to propene oxide: examination of the possible transition
      structures.
AB  - The addition reaction of monomeric lithium enolate (Z)-1, derived from
      propiophenone, to propene oxide 2, was examined to clarify the exact geometry of
      the transition state (TS) involved in this type of reaction. The eight possible
      TSs and the corresponding pathways, four leading to syn gamma-hydroxy ketone
      (gamma-HK) 3 and four leading to anti gamma-HK 4, were compared, using the
      B3LYP/6-31+G(d)//B3LYP/6-31+G(d) theory level in vacuo and in the presence of the
      reaction solvent (toluene/hexane). In every case, the favored pathway involves a
      TS where the enolate C=C and the epoxide C-C are in a gauche relationship and
      where the Li(+) is stabilized by some C-C and C-H sigma bonds of epoxide 2.

PMID- 14703392
TI  - Functionalization of OEP-based benzochlorins to develop carbohydrate-conjugated
      photosensitizers. Attempt to target beta-galactoside-recognized proteins.
AB  - meso-(2-Formylvinyl)octaethylporphyrin on reaction with cyanotrimethylsilane in
      the presence of various catalysts [copper triflate [Cu(OTf)(2)], indium triflate
      [In(OTf)(3)], or magnesium bromide diethyl etherate (MgBr(2).Et(2)O)] produced a
      mixture of the intermediate 3-hydroxy-3-cyanopropenoporphyrin, the corresponding
      trimethylsilyl ether derivative, and the unexpected propenochlorins. The yields
      of the reaction products were found to depend on the reaction conditions and the
      catalysts used. The intermediate porphyrins on treatment with concentrated
      sulfuric acid yielded the free-base cyanobenzochlorins in major quantity along
      with several other novel benzochlorins as minor products. Reduction of ethyl-3
      hydroxy-1-pentenoate-porphyrin with DIBAL-H/NaBH(4) and subsequent acid treatment
      provided the corresponding free-base 10(3)-(2-hydroxyethyl)benzochlorin, which
      upon a sequence of reactions gave a free-base benzochlorin bearing a carboxylic
      acid functionality in good yield. It was then condensed with a variety of
      carbohydrates (glucosamine, galactosamine, and lactosamine), and the related
      conjugates were screened using the galectin-binding-ability assay. Among the
      carbohydrate conjugates investigated, the lactose and galactose analogues
      displayed the galectin-binding ability with an enhancement of about 300-400-fold
      compared to lactose. In preliminary studies, all photosensitizers (with or
      without carbohydrate moieties) were found to be active in vitro [radiation
      induced fibrosarcoma (RIF) tumor cells]. However, the cells incubated with
      lactose (known to bind to beta-galactoside-recognized proteins) prior to the
      addition of the photosensitizers containing the beta-galactose moiety (e.g.,
      galactose and lactose) produced a 100% decrease in their photosensitizing
      efficacy. Under similar experimental conditions, benzochlorin without a beta
      galactoside moiety or the related glucose conjugate did not show any inhibition
      in its photosensitizing efficacy. These results in combination with the galectin
      binding data indicate a possible beta-galactoside-recognized protein specificity
      of the galactose- and lactose-benzochlorin conjugates.

PMID- 14703393
TI  - Thermodynamics of the molecular and chiral recognition of cycloalkanols and
      camphor by modified beta-cyclodextrins possessing simple aromatic tethers.
AB  - The complex stability constants (K(S)) and thermodynamic parameters (DeltaG
      degrees, DeltaH degrees, and TDeltaS degrees ) for 1:1 inclusion complexation of
      beta-cyclodextrin (beta-CD) derivatives, 6-O-phenyl-beta-CD (2) 6-O-(4-formyl
      phenyl)-beta-CD (3), 6-O-(4-nitrophenyl)-beta-CD (4), 6-O-(4-bromophenyl)-beta-CD
      (5), 6-O-(4-chlorophenyl)]-beta-CD (6), and 6-O-(4-hydroxybenzoyl)-beta-CD (7)
      with representative guest molecules, cyclic alcohols (cyclopentanol,
      cyclohexanol, cycloheptanol, cyclooctanol), (+/-)-borneol, and (+/-)-camphor,
      have been determined by means of titration microcalorimetry in an aqueous
      phosphate buffer solution (pH = 7.20) at 298.15 K. The results obtained indicate
      that the introduction to beta-CD of an aromatic ring bearing different
      substituent groups significantly enhances the molecular binding ability and
      moderately alters the chiral discrimination ability for the guests examined here,
      displaying the highest enantioselectivity of up to 4.01 for the inclusion
      complexation of 6 with (+/-)-camphor. The enhanced molecular/chiral
      discrimination ability caused by derivatization is attributed solely to increased
      positive entropy changes due to the expanding hydrophobic interaction and
      desolvation effects. The binding modes of host-guest interactions derived from
      ROESY spectroscopy data show that the resulting complex of 4 and (+)-borneol
      possesses better induced-fit interaction as compared to (-)-borneol, which is
      responsible for the enhanced molecular/chiral recognition ability.

PMID- 14703394
TI  - New Hg2+-selective chromo- and fluoroionophore based upon 8-hydroxyquinoline.
AB  - A new 8-hydroxyquinoline derivative having an appended boron-dipyrromethene
      function has been prepared, and its metal ion sensing properties were
      investigated. The designed compound exhibited pronounced Hg(2+)-selective on-off
      type fluoroionophoric properties among the representative transition- and heavy
      metal ions in aqueous dioxane solution. The fluorescence was efficiently quenched
      more than 98% with 5 equiv of Hg(2+) ions, and the detection limit was found to
      be 5 x 10(-)(6) M in a dioxane-water (1:3, v/v) solvent system. The ionophore
      also showed a selective chromogenic behavior toward Hg(2+) ions by changing the
      color of the solution from light amber to red, which can be detected with the
      naked eye.

PMID- 14703395
TI  - Avenues into the synthesis of illusive poly(m-phenylene-alt-squaraine)s:
      polycondensation of m-phenylenediamines with squaric acid intercepted by
      intermediate semisquaraines of exceptionally low reactivity.
AB  - The synthesis and properties of a novel class of ortho-dialkylamino-substituted
      semisquaraines are described. The exceptionally low reactivity of the
      investigated compounds is caused by an intramolecular hydrogen bond as evidenced
      by experimental and computational studies. Although this constitutes the reason
      for our failed attempts to prepare poly(m-phenylene-alt-squaraine)s, the
      discovered influence of hydrogen bonding on the photophysical properties of these
      semisquaraines provides a promising new motif for sensor design.

PMID- 14703396
TI  - One-pot synthesis and conformational features of n,n'-disubstituted ketene
      aminals.
AB  - N,N'-Disubstituted ketene aminals are bioisosteres of thioureas and are useful
      building blocks in many synthetic operations. A convenient one-pot synthesis of
      N,N'-disubstituted ketene aminals from activated methylene compounds and
      isothiocyanates is described. Most of these aminals exist in rotameric
      equilibrium around the central C=C bonds in solution, and the rotamers are
      stabilized by intramolecular hydrogen bonding both in solution and in solid
      states.

PMID- 14703397
TI  - An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331
      and the reassessment of the absolute configuration.
AB  - GT-2331 is a potent histamine H(3) antagonist which has entered clinical trials.
      Efficient multigram syntheses of this compound and its enantiomer are described.
      The literature reports that GT-2331 is the dextrorotatory (+), more potent,
      enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the
      absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory,
      more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole
      has the (1S,2S) absolute configuration. We suggest a reconsideration of the
      absolute configuration of GT-2331.

PMID- 14703398
TI  - Binding of imidazole-derived nucleosides to a CG base pair.
AB  - Novel imidazole nucleosides with substituents of different flexibility were
      studied for their binding to a CG Watson-Crick base pair by (1)H NMR spectroscopy
      in an aprotic solvent. Thermodynamic data as determined by titration experiments
      at different temperatures reveal the influence of the substituent on the enthalpy
      and entropy of complex formation and thus on the strength of binding.

PMID- 14703399
TI  - New and efficient syntheses of alpha-iodo-alpha,alpha-difluoro- and beta-iodo
      alpha,alpha,beta,beta-tetrafluorocarboxylic acid derivatives as useful building
      blocks for making functional fluoro compounds.
AB  - Perfluoroolefins reacted with I-Cl and ClSO(3)H under mild conditions to give
      R(F)CFICF(2)OSO(2)Cl, which could be readily converted into various alpha-iodo
      perfluorocarboxylic acid derivatives or telomerized with tetrafluoroethylene to
      I(CF(2)CF(2))(n)()OSO(2)Cl. Ring-opening reaction of
      perfluoroalkoxypentafluorocyclopropane with iodine at 240 degrees C produced
      ICF(2)CF(2)COF, which was quenched by alcohol, water, or NH(3) to give beta-iodo
      alpha,alpha,beta,beta-tetrafluorocarboxylic acid derivatives. These functional
      fluorinated iodides can be used as building blocks for making selectively
      fluorinated compounds.

PMID- 14703400
TI  - Reactivity of 2-deoxy-2-iodoglycosyl isothiocyanates with O-, S-, and N
      nucleophiles. Synthesis of glycopyranoso-fused thiazoles.
AB  - The reactivity of 2-deoxy-2-iodoglycosyl isothiocyanates toward O- and S
      nucleophiles gives an easy access to 2-deoxy-2-iodoglycopyranosyl thiocarbamates
      and dithiocarbamates. Internal nucleophilic displacement of the iodine by the
      sulfur atom in these compounds allows the preparation of glycopyranoso[1,2-d]-1,3
      thiazoles and glycopyranoso[1,2-d]-1,3-thiazolidin-2-one or -2-thione. Reaction
      with amines or polyamines as N-nucleophiles led directly to 2
      aminoglycopyranoso[1,2-d]-1,3-thiazoles without isolation of the intermediate
      thioureas. Methyl 2-deoxy-2-iodoglycopyranosyl thiocarbamates also allow the
      synthesis of 2-deoxyglycopyranosyl thiocarbamates or 2-deoxy-2-iodoglycopyranosyl
      carbamates.

PMID- 14703401
TI  - Preparation of both antipodes of enantiopure inherently chiral calix[4]crowns.
AB  - Both antipodes of enantiopure inherently chiral calix[4]crown derivatives were
      successfully obtained through separation of their BINOL diastereomeric
      derivatives of corresponding racemates using preparative TLC instead of
      conventional HPLC methods. Such a result provides a basis for future study of
      chiral recognition and asymmetric catalysis with inherently chiral calixrene
      derivatives.

PMID- 14703402
TI  - Transesterification/Acylation of secondary alcohols mediated by N-heterocyclic
      carbene catalysts.
AB  - N-Heterocyclic carbenes (NHC) are efficient catalysts for
      transesterification/acylation reactions involving secondary alcohols. The
      catalytic transformations are carried out employing low catalyst loadings in
      convenient reaction times at room temperature.

PMID- 14703403
TI  - Simple synthesis of substituted pyrroles.
AB  - Simple synthesis of substituted pyrroles using iodine-catalyzed and
      montmorillonite KSF-clay-induced modified Paal-Knorr methods has been
      accomplished with excellent yields. N-Substituted carbazole has also been
      prepared by following this method. If one of the reactants is a liquid, the
      reaction proceeds exceedingly well without a solvent. This method gives pyrroles
      with less nucleophilic multicyclic aromatic amines at room temperature.

PMID- 14703404
TI  - Linear free energy correlation analysis on the electronic effects of Rh(II)
      carbene O-H insertion.
AB  - The relative rate constants for the Rh(II)-catalyzed insertion of diazoacetone
      into the O-H bond have been measured through intermolecular competitions. The
      kinetic data were subjected to Hammett correlation analysis, and mechanistic
      implication of the results with respect to a stepwise vs a concerted O-H
      insertion pathway is discussed.

PMID- 14703405
TI  - Improved yields with added copper(I) salts in carbonylative stille couplings of
      sterically hindered vinylstannanes.
AB  - Stille coupling under standard carbonylative conditions proceeds in poor yield
      when using hindered alkenylstannane and enol triflate partners. The inclusion of
      35 mol % CuI or CuBr significantly improves the efficiency of the coupling,
      providing a variety of complex 1,4-dien-3-ones in good to excellent yield.

PMID- 14703407
TI  - Recent reviews. Number 71.

PMID- 14703408
TI  - [Treatment of head and neck squamous cell carcinoma by recombinant adenovirus-p53
      combined with radiotherapy: a phase II clinical trial of 42 cases].
AB  - OBJECTIVE: To evaluate the efficacy and safety of recombinant adenovirus-p53
      (Adp53, SBN-1) combined with radiotherapy in treatment of head and neck squamous
      cell carcinoma (HNSCC). METHODS: Forty-two patients with HNSCC were randomly
      divided into 2 groups: gene therapy + radiotherapy group (GTRT group. n = 20, SBN
      1 solution 1 x 10(12) VP was injected intratumorally once a week for 8 weeks and
      radiotherapy was begun since the 3rd day of gene therapy 5 fractions a week with
      the with the fraction dosage of 2 Gy and total dosage of 70 GY) and radiotherapy
      group (RT group. n = 22, the above regimen of radiotherapy was conducted). CT was
      conducted 5 weeks and 8 weeks after the beginning of treatment and 2 months after
      the finish of treatment (validation point) to calculate the size of tumor.
      Patients were monitored for adverse event and serum level of anti-adenoviral
      antibody. A comparative study was also performed on the immediate response rate
      by CT at the times when the dosages of 40 Gy and 70 Gy had been given. RESULTS:
      The average tumor reduction rates were (63 +/- 17)%, (82 +/- 18)%, and (90 +/-
      16)% at the 40 Gy time point, 70 Gy time point, and validation point respectively
      in the GTRT group, all higher than those in the RT group (37 +/- 26)%, (62 +/-
      39)%, and (70 +/- 34)% respectively, all P < 0.05. Random control study showed
      that the radio-sensitized enhancement rate was 1.72 at 40 Gy time point and the
      CR rate of the GRTR group at the validation point was 1.68 times higher than that
      of the RT group. Self-controlled study showed that the SBN-1 radio-sensitized
      enhancement ratio in the 4 GTRT group was 1.69 at 40 Gy time point and the CR
      rate of the GTRT group at validation point was 253% that of the RT group (P <
      0.01). No dose-limiting toxicity and adverse events were noted, except transient
      fever after SBN-1 administration. CONCLUSION: A potentially effective gene
      therapeutic agent for HNSCC treatment, intratumoral injection of SBN-1 is safe.

PMID- 14703409
TI  - [Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: phase
      I clinical trial and follow up].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of recombinant adenovirus p53
      injection (SBN-1) in patients with laryngeal cancer. METHODS: Twelve cases with
      laryngeal cancer, 11 males and 1 female, aged 59.5 +/- 12.4 years, were randomly
      divided into three groups of 4 patients. The patients received intratumor
      injection of SBN-1 at the dosage of 1 x 10(10)VP, 1 x 10(11)VP, or 1 x 10(12)VP
      once every other day for 2 courses of treatment with 5 times of injection as one
      course of treatment. Two days after the injection the patients were operated on.
      After the operation SBN-1 of the same doses was injected around the tumor bed.
      The patients were followed up for more than 3 years by correspondence and out
      patient department examinations. ELISA was used to detect the serum anti
      adenoviral IgG and IgM, and interleukin-2 receptor (IL-2R). Immunohistochemistry
      was used to examine the expression of p53 protein in the tumor tissues. Flow
      cytometry was used to examine the T cell subgroup. The symptoms and side effects
      were observed. RESULTS: One patient in the 10(12)VP group presented self-limited
      fever (38.2-38.6 degrees C) and no other abnormality was observed after the SBN-1
      injection. Specific antibody to SBN-1 turned from negative to positive two or
      three weeks after the first injection. P53 protein expression was significantly
      enhanced in tumors after injection of SBN-1. The serum level of IL-2R was 750 +/-
      401 pg/ml before treatment and 552 +/- 203 pg/ml after treatment. The numbers of
      CD3, CD4, and CD8 were 66 +/- 10, 41 +/- 15, and 32 +/- 10 respectively before
      the treatment and were 67 +/- 9, 43 +/- 8, and 34 +/- 16 respectively after
      treatment, and the CD4/CD8 ratio was 1.4 +/- 0.6 before the treatment and was 1.6
      +/- 0.9 after treatment. The abnormality in SIL-2R level and the disorder of T
      cell subgroup were improved in 2 cases. Followed up for over 3 years showed that
      all cases still lived free of cancer. CONCLUSION: Safe and effective on laryngeal
      cancer without obvious adverse events, local injection of SBN-1 is a promising
      treatment.

PMID- 14703410
TI  - [Recombinant adenovirus p53 agent injection combined with radiotherapy in
      treatment of nasopharyngeal carcinoma: a phase II clinical trial].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of recombinant adenovirus p53
      agent (SBN-1) combined with radiotherapy in treatment of nasopharyngeal
      carcinoma. METHODS: Twenty-nine cases with nasopharyngeal carcinoma were randomly
      divided into two groups: gene therapy + radiotherapy group (GTRT group, n = 16,
      SBN-1 was injected intratumorally once a week for 8 weeks, and radiotherapy with
      the dosage of 60-70 Gy was given 3 days after the first injection of SBN-1) and
      radiotherapy group (RT group, n = 213, the same regimen of radiotherapy was given
      only). CT and MRI were conducted 4, 8, and 12 weeks after to evaluate the size of
      tumor. Then the patients were followed-up every month. Toxicity was evaluated by
      physical examination, KPS scoring, blood, urine, and feces routines, serum BUN,
      creatine, AST, ALT, LDH, and AKP, electrocardiography, and X-ray. RESULTS: The
      tumors of the patients group were reduced by 70.9 +/- 18.1% and 49.4 +/- 22.8% in
      the GTRT group and the RT group respectively (P < 0.001) 4 weeks after treatment;
      and were reduced by 94.9 +/- 10.2% and 80.4 +/- 17.0% in the GTRT group and RT
      group respectively (P < 0.001) 8 weeks after treatment. The rates of complete
      regression of tumor 12 weeks after the treatment were 75% and 15% in the GTRT
      group and RT group respectively (P < 0.005). 3 cases presented mild, self-limited
      fever and no other side effects were noted. CONCLUSION: Local injection of SBN-1
      combined with radiotherapy to treat nasopharyngeal carcinoma is safe and
      significantly more effective than single radiotherapy.

PMID- 14703412
TI  - [Design and preliminary clinical application of general spine system].
AB  - OBJECTIVE: To evaluate the efficacy of self-designed General Spine System (GSS)
      through the measurement of the biomechanical characteristics and the outcomes of
      preliminary clinical application. METHODS: The General Spine System implants were
      made of titanium alloy (TC4, Ti6Al4V) and the instruments were made of stainless
      steel after design. Pull-out strength of GSS screw, CCD, SOCON, TSRH and Diapason
      screw were tested in fresh normal cadaveric spine specimens respecting and the
      biomechanical stability analyses of GSS and SOCON were also tested. GSS was
      applied clinically in 16 patients with degenerative lumbar spondylolisthesis
      combined with lumbar canal stenosis. Clinical efficacy, reduction effectiveness,
      and complications were recorded. RESULTS: The pull-out strength of GSS screw was
      more than other control screws. Biomechanical stability of GSS was similar to
      SOCON system. Average postoperative follow-up for all patients was 12.6 months
      (11.5-14.5 months). All patients got satisfied clinical results at the latest
      follow-up. X-ray results showed complete reduction for all spondylolisthesis
      patients, and results remained good in follow-up. Complications related to
      implants or operation were not observed after surgery or in follow-up.
      CONCLUSION: GSS pedicle screws have strong anchoring ability and good
      stabilization for spondylolisthesis. This system can provide good reduction for
      spondylolisthesis. Its clinical efficacy is confirmed.

PMID- 14703411
TI  - [An epidemiological study on the relationship between selenium and thyroid
      function in areas with different iodine intake].
AB  - OBJECTIVE: To investigate the relationship between selenium status and thyroid
      dysfunction in 3 areas with different iodine intake. METHODS: An epidemiological
      research was performed in the rural communities of Panshan County (iodine
      deficient area) and Zhangwu County (iodine-sufficient area), Liaoning Province,
      and Huanghua County, Hebei Province (iodine-excessive area). Serum selenium, TSH,
      FT3 and FT4 levels were examined in 329 patients with thyroid dysfunction
      (including clinical hypothyroidism, subclinical hypothyroidism, clinical
      hyperthyroidism and subclinical hyperthyroidism) and 183 normal inhabitants.
      RESULTS: The median serum selenium concentrations in Panshan, Zhangwu and
      Huanghua were 91.4, 89.1, and 83.2 microg/L respectively. There was no difference
      in serum selenium levels between the patients with subclinical hypothyroidism,
      clinical hypothyroidism, and clinical hyperthyroidism and their normal controls.
      The median serum selenium concentration of the subclinical hyperthyroidism
      patients was 82.6 microg/L, significantly lower than that of the normal controls
      (87.3 microg/L). The FT3/FT4 ratio was decreased, the FT4 level was increased in
      the subclinical hyperthyroidism patients in comparison with the normal controls,
      and no significant difference in FT3 level was found between them. No significant
      effect of sex and age was found on serum selenium level of normal inhabitants. In
      normal controls serum selenium was inversely correlated with serum TSH level, and
      the subjects with serum selenium < or = 80 microg/L had the median TSH level of
      2.10 mU/L, markedly higher than that of the subjects with the serum selenium of
      80-100 microg/L (1.29 mU/L) and that of the subjects with the serum selenium of
      100 approximately 120 micro g/L (1.28 mU/L). For the thyroid dysfunction patients
      with positive thyroid auto-antibody (TPOAb) in Zhangwu County, the serum selenium
      was negatively associated with TPOAb level. The serum selenium level of the TPOAb
      highly positive group (TPOAb > 600 IU/ml) was 83.6 IU/ml, significantly lower
      than those of the TPOAb lowly positive group and TPOAb moderately positive group
      (83.6, 92.9 and 95.6 microg/L respectively). CONCLUSION: No obvious effect of
      selenium status is found on the development of thyroid dysfunction in these three
      areas. But selenium deficiency can impair thyroid function by means of disturbing
      thyroid hormone metabolism and decreasing antioxidant ability of the thyroid.

PMID- 14703413
TI  - [Efficacy of gamma knife radiosurgery in treatment of growth hormone-secreting
      pituitary adenoma].
AB  - OBJECTIVE: To evaluate the efficacy of gamma knife radiosurgery (GKS) in
      treatment of growth hormone (GH)-secreting pituitary adenoma. METHODS: 149
      patients with GH-secreting pituitary adenoma, 97 males and 52 females, aged 42.8
      (12-72 years), with a course of 6-240 months (72.5 months) and with the mean
      volume of tumor of 2.36 cm(3) (0.11-12.7 cm(3)) were treated by GKS. The mean
      dose to tumor margin was 20.87 Gy (10-30 Gy). 124 of them were followed up for 30
      months (6-72 months). RESULTS: The serum GH returned normal in 74 patients
      (64.9%) and declined in comparison with the level before radiosurgery in 23
      patients (18.5%). The tumor volume was reduced in 84 patients (67.7%) and
      remained unchanged in 124 patients (32.4%). Ambiopia appeared in one patient. No
      other complication was found during the follow-up. CONCLUSION: GKS is safe and
      effective on the treatment of GH-secreting pituitary adenoma.

PMID- 14703414
TI  - [Identification of immunological effector cells after autologous cytokine-induced
      killer cells treatment and its clinical implication in hepatocellular carcinoma
      patients].
AB  - OBJECTIVE: To investigate the alteration of the cellular profiles of T lymphocyte
      subsets and dendritic cell subsets in peripheral blood of primary hepatocellular
      carcinoma (HCC) patients after being transfused with autologous cytokine-induced
      killer cells (CIK) in patients, then to evaluate the clinical efficacy of the
      immune therapeutic strategy. METHODS: Peripheral blood mononuclear cells (PBMCs)
      from 13 patients with primary were collected using blood cell separator, and
      expanded in the fresh AIM-V medium in the presence of cytokine cocktail including
      interferon-gamma (IFN-gamma), monoclonal antibody (mAb) against CD3 and
      interleukin-2 (IL-2). The phenotypic patterns of CIK cells were longitudinally
      characterized by flow cytometry on day 0, 4, 7, 10,13 and 15 during the
      incubation period. PBMCs obtained from HCC patients before or after CIK cells
      transfusion into bodies to assay the changes of proportion of DC1 or DC2 in
      peripheral blood. RESULTS: After in vitro incubation for 14 or 15 days, a large
      of CD3(+)CD56(+) cells were produced from their progenitors and the percentages
      of CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells significantly increased from 33.5%
      +/- 10.1%, 7.7% +/- 2.8%, and 12.3% +/- 4.5% at the beginning to 36.6% +/- 9.0%
      (P < 0.05), 18.9% +/- 6.9% (P < 0.01), and 16.4% +/- 5.9% (P < 0.05) at the day
      15, respectively. In contrast, the percentages of CD3(+)CD4(+) and NK cells
      displayed no significant difference. The percentages of CD3(+), CD3(+)CD8(+)
      cells was held at a higher level during the whole incubation period, however
      those of the CD25(+), and CD3(+)CD56(+) cells began decreasing on day 7 and day
      13, respectively. The proportion of type I of dendritic cells (DC1) and type II
      of dendritic cells (DC2) subsets increased from 0.59% +/- 0.23% and 0.26% +/-
      0.12% before CIK cell transfusion to 0.85% +/- 0.27% and 0.43% +/- 0.20% (all P <
      0.01) after CIK cell transfusion. The symptom of HCC patients receiving the CIK
      cell therapy was markedly ameliorated, and not side effect was seen in the
      treatment. CONCLUSION: Our results indicated that autologous CIK cells is able to
      boost the cellular immunological function in HCC patients, which probably provide
      a potent immune therapeutic strategy for HCC patients.

PMID- 14703415
TI  - [Genetic analysis of a Chinese family with inherited afibrinogenemia].
AB  - OBJECTIVE: To identify the mutations of fibrinogen genes in a Chinese family with
      inherited afibrinogenemia. METHODS: Samples of peripheral blood were collected
      from 17 members of 3 generations in a Chinese family with inherited
      afibrinogenemia, including the proband, female, aged 8. All the exons and exon
      intron boundaries of the three fibrinogen genes were analyzed by direct
      sequencing. RESULTS: The sequencing results of the proband revealed compound 2
      heterozygous mutations in fibrinogen FGA gene, one being a splice mutation
      (g.1892-1899delAGTAorGTAA) in the boundary between exon3 and intron3 of the FGA
      gene and traced back to her patriline and the other being a 1,238 bp large
      deletion (g.1978-3215) in the same gene and originating from her matriline.
      CONCLUSION: Inherited afibrinogenemia is caused by the compound heterozygous
      deletion in the fibrinogen FGA gene.

PMID- 14703416
TI  - [Preventive effects of ramosetron and granisetron in prevention of
      gastrointestinal reaction associated with chemotherapeutic agents: a comparative
      study].
AB  - OBJECTIVE: To compare the efficacy and safety of ramosetron and granisetron in
      prevention of gastrointestinal reaction induced by cisplatin or adramycin.
      METHODS: Fifty chemotherapy-naive patients with histological confirmed
      malignancies were randomized divided into 2 groups: AB group (ramosetron 0.3 mg
      was given in first cycle and granisetron 3mg in the second cycle) and BA group
      (these drugs were given in the reverse sequence). The appetite, side effects,
      such as nausea, vomiting, headache, dizziness, etc. were observed. RESULTS: A
      total of 47 patients, 27 receiving cisplatin and 20 receiving adramycin, were
      evaluable. 0-24 hours after the treatment, the inhibition rate of anorexia was
      72.3% in the ramosetron group, significantly lower than that in the granisetron
      group (51.1%, P < 0.05). The inhibition rate of nausea was 66.0% in the
      ramosetron group, significantly lower than that in the granisetron group (44.6%,
      P < 0.05), and the inhibition rate of vomiting was 76.6% in the ramosetron group,
      not significantly different from that in the granisetron group (70.2%). The
      incidence rate of adverse events was similar in these two groups. The most common
      adverse event was headache. CONCLUSION: Ramosetron is a safe and effective
      antiemetic and is more cost-effective than granisetron.

PMID- 14703417
TI  - [Aprotinin reduces myocardial injury in the off-pump coronary artery bypass
      grafting].
AB  - OBJECTIVE: To investigate the effect of aprotinin on the myocardial injury during
      the off-pump coronary artery bypass grafting (OPCAB). METHODS: Twenty-four
      patients undergoing OPCAB randomly were of 12 patients divided into two groups:
      aprotinin group and Control group (n = 12). In the aprotinin group a loading dose
      (2 x 10(6) KIU) was administered within the first 30 minutes after the induction
      followed by continuous infusion of 0.5 x 10(6) KIU/h throughout the operation.
      The plasma myocardial injury markers CK-MB and cTnI were measured at the four
      points: (1) After induction; (2) 1 hour after coronary anastomosis; (3) 6 hours
      and (4) 24 hours after the operation. The blood loss was recorded by
      autotransfusion in the operation, and the drainage immediately, 6 hours, and 24
      hours after the operation. RESULT: Myocardial injury markers CK-MB and cTnI
      increased significantly after the anastomosis in each group; cTnI was lower in
      the aprotinin group than in the control group at the third and forth points (P <
      0.05). The post-operative drainage after 6 hours and 24 hours were lower in the
      aprotinin group than in control group (P < 0.05). CONCLUSIONS: There is the
      myocardial injury during OPCAB. Aprotinin can reduce the myocardial injury during
      OPCAB.

PMID- 14703418
TI  - [Clinical application of posturography with inclinometer and platform with global
      bottom].
AB  - OBJECTIVE: To investigate the efficacy of posturography with inclinometer and
      platform with global bottom to make the subjects contact the ground almost at one
      point in the evaluation of body balance function. METHODS: The body balance
      function of 100 normal persons, 50 males and 50 females, aged 21 approximately
      50, and 87 patients with peripheral vertigo due to semicircular canal palsy, aged
      20 approximately 60, was measured with a new type of posturograph with
      inclinometer and platform with global bottom developed by the authors. The
      subjects with an inclination-sensor being fixed at the waist were asked to adopt
      four postures during the measurement: standing on the ground with eyes opened
      (test 1), standing on the ground with the eyes closed (test 2), standing on the
      platform with the eyes opened (test 3), and standing on the platform with the
      eyes closed (test 4). RESULTS: The measurement of the normal persons showed the
      average values of body sway angle velocity were 0.57 +/- 0.24 d/s in test 1, 0.70
      +/- 0.18 d/s in test 2, 1.16 +/- 0.32 d/s in test 3, and 2.67 +/- 0.70 d/s in
      test 4. Sixty-two out of the 87 patients (71.26%) showed abnormality in one or
      more than one of the 4 tests with a value more than x +/- 2s of the normal value,
      among them 7 showed abnormal value in test 1, 14 in test 2, 16 in test 16, and 56
      in test 4. Two weeks after the onset of vertigo, 55 out of the 87 patients showed
      abnormal values by this examination. CONCLUSION: Posturography with inclinometer
      and platform with global bottom is effective on evaluation of balance function,
      In particular, the test of standing on the platform with the eyes closed
      effectively reflects the vestibulospinal reflex.

PMID- 14703419
TI  - [Peroxisome proliferation-activated receptor-gamma ligands ameliorate autoimmune
      myocarditis associated with inhibition of T cell immunity].
AB  - OBJECTIVE: To investigate the role of peroxisome proliferator-activated receptor
      gamma (PPAR gamma) on autoimmune myocarditis, and to test the hypothesis that
      PPAR-gamma ligands reduce experimental autoimmune myocarditis (EAM) associated
      with inhibition of the expansion and activation of self-sensitive T cells.
      METHODS: EAM was induced in Lewis rats by immunization with porcine cardiac
      myosin. Then the rats were divided into 3 groups of 9 rats: PPAR-gamma ligand 15
      deoxy-(12,14)-PGJ(2) (15d-PGJ(2)) group (15d-PGJ(2) was injected
      intraperitoneally at the dosage of 200 microg.kg(-1).d(-1)), pioglitazone (PIO)
      group (PIO was mixed with the food and than fed at the dosage of 10 mg.kg(-1).d(
      1)), and positive control group (phosphate-buffered saline was injected
      intraperitoneally). Nine normal rats were used as normal controls. Three weeks
      later, the rats underwent thoracotomy to undergo pathologic examination. The
      numbers of CD4(+) cells, CD8(+) cells, and macrophages were calculated by
      microscopy. Immunohistochemistry was used to examine the location and expression
      of PPAR gamma. Western blotting was used to examine the relative amount of PPAR
      gamma protein. The proliferative response and the cytotoxicity of T cell-enriched
      splenocytes and lymph node cells were determined. Another rats were killed 12
      days after immunization. Their spleens and lymph nodes were taken out. T-cell
      rich splenocytes and cells from the lymph nodes were cultured. Cardiac myosin and
      15d-PGJ(2) were added. [(3)H] thymine was added 72 hours after. ELISA was used to
      examine the interferon-gamma (IFN-gamma) in the supernatant. 15d-PGJ(2), PIO, or
      PBS were given to immunize the rats. The rats were killed 12 days after. The
      lymph nodes were taken out to make single cell suspension. (51)Cr was used to
      label the cells so as to calculate the %cytotoxicity. RESULTS: All immunized rats
      showed myocarditis. The numbers of CD4(+) cells, CD8(+) T cells, and macrophages,
      were 18 +/- 5, 7 +/- 2, and 45 +/- 8/six 0.25 mm x 0.25 mm squares. PPAR gamma
      was mainly located in the nuclear and perinuclear regions of infiltrating
      inflammatory cells, such as mononuclear cells and macrophage-like cells. The
      expression of PPAR gamma in the myocardium of EAM rats was 3.7 times higher than
      of the normal rats. The heart weight/body weight ratio, pericardial effusion
      scores, macroscopic scores and microscopic scores of the 15d-PGJ group were
      significantly lower than those of the positive control group. The numbers of
      CD4(+) cells of the 15d-PGJ and PIO groups were 8 +/- 2 and 10 +/- 3, both
      significantly lower than that of the positive control group (both P < 0.01), the
      numbers of CD8(+) cells of the 15d-PGJ and PIO groups were 3 +/- 1 and 4 +/- 2
      respectively, both significantly lower than that of the positive control group (P
      < 0.01 and P < 0.05), and the numbers of macrophages of the 15d-PGJ and PIO
      groups were 22 +/- 4 and 26 +/- 6 respectively, both significantly lower than
      that of the positive control group (both P < 0.01). The myocardiogenicity and the
      severity of myocarditis of the 15d-PGJ(2)- and PIO-groups were at lower degrees
      compared with those of the positive control group. The % cytotoxic activity was
      10.2% +/- 2.6% in the 15d-PGJ(2) group and was 11.6% +/- 3.7% in the PIO group,
      both significantly lower than that of the positive control group (37.7% +/- 8.4%,
      both P < 0.01) Stimulated by cardiac myosin, the T-cell rich splenocytes and
      cells from lymph nodes showed obvious proliferation and production of IFN-gamma.
      The cardiac myosin-stimulated cell proliferation and production of IFN-gamma in
      the 15d-PGJ(2) and PIO groups were significantly reduced in comparison with those
      in the positive control group. CONCLUSION: PPAR-gamma ligands ameliorate EAM
      associated with inhibition of expansion and activation of the self-sensitive T
      cells.

PMID- 14703420
TI  - [Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon
      cancer].
AB  - OBJECTIVE: To investigate the effect of magnetic doxorubicin liposome (MDL) in
      the targeting treatment of nude mice bearing colon cancer. METHODS: Human colon
      cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks
      after the mouse was killed and the tumor was taken out and cut into small pieces
      to be retransplanted into nude mice so as to establish an experimental model. MDL
      was prepared by reverse-phase evaporation method. The particle size and structure
      of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3
      groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to
      the tumor surface), and MDL (+) group (magnetic field with the strength of 4,500
      G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein
      in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence
      spectrophotometry was used to examine the concentrations of DOX in the tissues
      and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of
      6 mice: normal saline group (as controls), DOX group, blank liposome group,
      magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the
      tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The
      body weight, longest diameter of tumor, and short diameter vertical to the
      longest diameter were calculated regularly. The mice were killed 11 days after.
      The tumors were taken out to undergo staining and light microscopy. Flow
      cytometry was used to examine the apoptosis of tumor cells. RESULTS: The particle
      size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly
      distributed within the liposome. The DOX concentration in tumor tissue of the MDL
      (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P
      < 0.05). The DOX concentration in heart and kidney of the DOX group were higher
      than those of the other 2 groups, and the plasma DOX concentrations of the DOX
      group was significantly lower than those of the other groups (all P < 0.05). The
      growth speed of tumor in the MDL (+) group was significantly lower, and the tumor
      weight was significantly less than in other groups. CONCLUSION: Magnetic
      doxorubicin liposome, as a carrier of anticancer drug, has a good targeting
      function toward the magnetite and has a significant anticancer effect.

PMID- 14703421
TI  - [The study of 5-Aza-2'-deoxycytidine on transcription regulation of p16/CDKN2
      gene demethylation in RKO human colorectal cell line].
AB  - OBJECTIVE: To explore the transcription regulation of DNA 5'CpG island
      demethylation on p16/CDKN2 tumor suppressor gene and effects of growth on RKO
      human colorectal cancer cell line. METHODS: RKO cell line was exposed to the
      specific demethylating agent, 5-Aza-2'-deoxycytidine, for seventy-two hours to
      detect whether the silencing of p16/CDKN2 cell cycle regulatory gene could be
      reversed. Methylation-specific PCR (MSP), T-A cloning and sequence analysis were
      evaluated for methylation status. Growth speed, expression of DNA
      methyltransferase mRNA, p16/CDKN2 mRNA and protein were determined by MTT assay,
      reverse transcription polymerase chain reaction (RT-PCR), Real-time PCR,
      immunohistochemistry and western blot. RESULTS: (1) All cytosines in CpG
      dinucleotides in untreated RKO cells with 5-Aza-2'-deoxycytidine remain as C,
      while all cytosines in treated RKO cells have been converted to thymidine. (2)
      RKO cell line after treatment with three different concentration 5-Aza-2'
      deoxycytidine grew slowly and double time increased to 1.49, 1.64, 1.87-times
      respectively. (3) The expression of RKO cell p16/CDNK2 gene mRNA treated with 5
      Aza-2'-deoxycytidine increased to 4.89, 16.91, 19.97-times respectively, but the
      expression of DNA methyltransferase mRNA was inhibited. (4) Immunohistochemistry
      and western blot indicated that 5-Aza-2'-deoxycytidine could increase the
      p16/CDKN2 gene protein expression. CONCLUSION: DNA promoter hypermethylation is
      associated with p16/CDKN2 gene silence in RKO human colorectal cancer cell line.
      5-Aza-2'-deoxycytidine may effectively cause demethylation and inhibit the growth
      of tumor cell by reactivating the gene transcription silenced by aberrant
      hypermethylation.

PMID- 14703422
TI  - [Mechanism of percutaneous myocardial laser revascularization in the treatment of
      experimental cardiac ischemia].
AB  - OBJECTIVE: To evaluate the cardiac angiogenesis after percutaneous myocardial
      laser revascularization (PMR). METHODS: The left anterior descending coronary
      arteries of 10 healthy mongrel dogs weighing 14 - 18 kg were ligated partially so
      as to construct a model of chronic cardiac ischemia. Then the dogs were randomly
      divided into 2 groups of 5 dogs: PMR and control groups. Cardiogenesis Holmium:
      YAG laser system was used to make endomyocardial channels (15 +/- 3 channels/dog)
      in the ischemic ventricular walls in PMR group 2 weeks after the ligation. Sham
      procedure was conducted on the control group. Myocardial perfusion was examined
      by single photon emission computed tomography (SPECT) and left ventricle ejection
      fraction (LVEF) was examined by cardiac ultrasound before the ligation and 1, 4,
      and 12 weeks after PRM in the PMR group and before and 3, 6, and 14 weeks after
      the ligation in the control group. In the PRM group one dog was killed after the
      SPECT and LVEF examination 1 and 4 weeks after the PRM respectively and the
      remaining 3 dogs were killed after the SPECT and LVEF examination 12 weeks after
      the PRM. The dogs in the control group were killed after the SPECT and LVEF
      examination 14 weeks after the ligation. Myocardial pathology and cardiac
      angiogenesis analysis were conducted in both groups. RESULTS: Three months after
      PMR or coronary artery ligation, the SPECT scores of the PMR and control groups
      decreased from 3.2 +/- 0.6 and 3.1 +/- 0.5 to 0.3 +/- 0.2 and 1.2 +/- 0.3
      respectively (both P < 0.05), the LVEF of the 2 groups increased from 42.6 +/-
      6.5 and 43.2 +/- 8.7 to 55.8 +/- 7.6 and 42.6 +/- 6.5 respectively (both P <
      0.05). Microscopy showed that the amount of micrangii was 45.6 +/- 7.4
      vessel/field in the PMR region of the PRM group, significantly much more than
      that in the non-ischemic region of the PRM group (18.2 +/- 4.7), the ischemic
      region of the control group (21.4 +/- 5.6), and the non-ischemic region of the
      control group (17.3 +/- 6.9, all P < 0.05). CONCLUSION: PMR promotes angiogenesis
      in the ischemic myocardial wall, thus improving the blood perfusion of ischemic
      myocardium and global cardiac systolic function.

PMID- 14703423
TI  - [Transdermal fentanyl for the management of cancer pain: a survey of 1,664
      elderly patients].
AB  - OBJECTIVE: To evaluate the effects and side effects of transdermal fentanyl for
      the elderly patients with cancer pain. METHODS: A multicenter clinical test was
      conducted among 1,664 patients with cancer pain, aged 65 - 90 with a median age
      of 71, 879 (52.8%) of which used opioid for the first time, from 136 hospitals in
      23 provinces in China. All patients received transdermal fentanyl to treat cancer
      pain with the mean dose of fentanyl of 31.34 micro g/h (25 - 150 micro g/h)
      initially, and 40.59 micro g/h and 47.50 micro g/h (25 - 200 micro g/h) at day 15
      and day 30. They were asked to record the attacks of pain, quality of life, and
      any side effects of the treatment. RESULTS: The baseline pain intensity score was
      7.34. On days 1, 3, 6, 9, 15, and 30, the mean pain scores were decreased to
      3.82, 2.80, 2.43, 2.11, 1.83, and 1.64 (all P < 0.01) respectively. The effective
      rate was 97.18%. The fine life quality rate was 25.4% before treatment, and was
      71.15% and 73.04% at day 15 and day 30 (both P < 0.01). The commonest side
      effects included constipation (10.70%), nausea (11.96%), dizziness (6.85%),
      vomiting (3.85%), sleepiness (2.40%), and respiratory depression (0.12%). The
      incidence of constipation was related with age, the incidence of vomiting and
      difficulty of urination was related with gender. 86.2% patients preferred to
      receive transdermal fentanyl. CONCLUSION: Safe, convenient, and capable to
      improve the quality of life, transdermal fentanyl is effective and worth
      recommending as a first-line drug for the treatment of elderly patients with
      moderate to severe cancer pain. The initial dose is recommended as 25 micro g/h.

PMID- 14703424
TI  - [Patient-controlled analgesia with tramadol and tramadol/droperidol mixture after
      abdominal hysterectomy: a double-blinded, randomized controlled trial].
AB  - OBJECTIVE: To compare the clinical efficacy and side effects of tramadol and the
      mixture of tramadol and droperidol for postoperative patient-controlled analgesia
      (PCA). METHODS: Sixty female patients, aged 18 - 65, scheduled for elective
      abdominal total hysterectomy with inhalational general anesthesia (induced with
      fentanyl and propofol, maintained with O(2)-N(2)O and enflurane or isoflurane
      supplemented by intermittent iv fentanyl and vercuronium for muscle relaxation)
      were allocated into 2 groups of 30 patients in a random and double blind manner:
      group 1 (20 mg tramadol) and group 2 (20 mg tramadol plus 0.1 mg droperidol),
      both with a lockout time of 10 minutes. The VAS, analgesic doses, and side
      effects were observed 4, 8, 12, 20, 28, and 36 hours after operation
      respectively. RESULTS: Adequate analgesia was achieved with tramadol or the
      mixture of tramadol and droperidol. The nausea rates and vomiting rates at any
      time point in the group 2 were all significantly lower than those in the group 1
      (all P < 0.05). Ten patients in the group 1 needed treatment of metoclopramide,
      and none of patients in the group 2 needed antiemetic (P < 0.01). No significant
      differences were observed in VAS, sedation score or vital signs (all P > 0.05).
      CONCLUSION: Providing a similar quality of analgesia with less nausea and
      vomiting as well as little need for sedative, the combination of tramadol and
      droperidol is superior to tramadol alone for post-operative PCA.

PMID- 14703425
TI  - [Association of small, dense low density lipoprotein with stroke].
AB  - OBJECTIVE: To investigate the relationship between small, dense LDL (sLDL) and
      stroke in Chinese population. METHODS: The plasma level of sLDL was examined by
      2% - 16% nondenatured gradient gel electrophoresis in 204 patients with stroke,
      including 103 cases of ischemic cerebral infarction (ICI), 51 cases of lacunar
      infarction (LI), and 50 cases of subcortical hemorrhage (SH), and in 341 sex- and
      age-matched controls in China. Traditional risk factors for stroke were
      investigated as well. RESULTS: The plasma level of sLDL was significantly higher
      in patients with ICI and LI (54 +/- 8% and 52 +/- 7%) than in the controls (47 +/
      11%, both P < 0.01). However, the plasma sLDL of the CH patients was 50 +/- 9%,
      not significantly different from that of the controls (P > 0.05). Multiple
      stepwise regression analysis showed that sLDL was significantly associated with
      systolic blood pressure, age, and the levels of triglyceride, high-density
      lipoprotein cholesterol, and low-density lipoprotein cholesterol (all P < 0.05).
      Multivariate logistic regression analysis showed that those with sLDL > 50% had
      increase of risk of ischemic cerebral infarction (OR = 3.1, 95% CI 1.649 - 5.691,
      P < 0.001) independent of other risk factors. The relationship between sLDL
      abnormality and LI and between sLDL abnormality and SH had no statistical
      significance (both P > 0.05). CONCLUSION: sLDL is significantly associated with
      ischemic cerebral infarction independent of other risk factors in Chinese
      population. sLDL may be a new marker for stroke at least in this Chinese
      population.

PMID- 14703426
TI  - [Experience in treatment of Raynaud's syndrome by chemical thoracic
      sympathectomy].
AB  - OBJECTIVE: To summarize the experience in treatment of Raynaud's syndrome with
      chemical thoracic sympathectomy (CTS) guided by X ray. METHODS: From March 2001
      to December 2002,35 cases (66 limbs) of Raynaud's syndrome were treated by CTS.
      Guided by X ray, a needle was punctured through the back skin to the second or
      third thoracic sympathetic ganglion beside the thoracic vertebrae and 2 ml of 5%
      phenol was injected. RESULTS: The first CTS treatment produced an excellent
      effect on 32 limbs, good effect on 12 limbs, and no effect on 22 limbs with an
      effective rate of 66.7% (44/66). The same treatment was performed on the limbs
      without effect 1 - 2 days after the first treatment and produce excellent effect
      on 2 limbs, good effect on 6 limbs, and no effect on 14 limbs with an effective
      rate of 36.4% (8/22). The efficiency rate of the first hospitalization was 78.8%.
      The effective rate of treating primary Raynaud's disease by CTS was 88.5% and
      that of treating secondary one was 42.8%. 85% of the patients were followed up
      for 9 months on average with an efficiency rate of 61%. CONCLUSION: CTS is mini
      invasive, cheap, easy to popularize, and a relatively ideal choice in treatment
      of Raynaud's syndrome. Complications can be minimum only if the operation is
      performed carefully.

PMID- 14703427
TI  - [Mastoscopic axillary lymph node dissection for the patients with breast cancer].
AB  - OBJECTIVE: To analyze the clinical effects of mastoscopic axillary lymph node
      dissection for the patients with breast cancer. METHODS: Following the
      liposuction of the axilla, axillary lymph node dissection was performed in 86
      breast cancer patients by mastoscopy. RESULTS: The median duration of operation
      was 55.3 min. The operation time was obviously shorter for the last 76 patients
      than for the first 10 patients (P < 0.001). The bleeding amount in operation was
      little, and no patient was intraoperatively transferred to routine open axillary
      lymph node dissection due to uncontrolled bleeding. A mean number of 15.3 lymph
      nodes were harvested. 37 patients showed involved lymph nodes. The mean number of
      involved lymph nodes in these patients was 3.6. There was no intra- and post
      operation morbidity. After a median follow-up time of 10.4 months, no axillary
      relapse or trocar site implantation had occurred. CONCLUSION: Mastoscopic
      axillary lymph node dissection (MALND) based on the liposuction of axilla is a
      minimally invasive and clinical feasible procedure. It manifests the functional
      and cosmetic effects and satisfies the breast cancer patients to certain extent.

PMID- 14703428
TI  - [Long term follow up of patients with knee osteoarthritis after high tibial
      osteotomy].
AB  - OBJECTIVE: To investigate the clinical result of knee osteoarthritis after high
      tibial osteotomy (HTO) in long term follow-up. METHODS: 107 patients of knee
      joint osteoarthritis performed with high tibial osteoarthritis between 1983 and
      2000 was followed up. Standing anteroposterior radiograph of knee were taken for
      every patient. RESULTS: The clinical results of 137 knees (88%) were rated as
      good at 1 to 5 years follow-up. 21 knees were good at 5 to 10 years follow-up.
      And 5 knees were good at lest 10 years follow-up. Only one patient was done TKA 8
      year after HTO. CONCLUSIONS: The patients done HTO show excellent clinical
      results in short time follow-up. And the results of most patients was maintained
      in intermediate and long-term follow-up. The internal fixition allow patients
      early activity and recover quickly.

PMID- 14703429
TI  - [A study of the degrees of insulin resistance and first-phase insulin secretion
      of beta-cells in metabolic syndrome patients with different glucose tolerance].
AB  - OBJECTIVE: To explore the insulin resistance and first-phase insulin secretion of
      beta-cells in normal persons, obese persons with normal glucose tolerance, obese
      persons with impaired glucose tolerance (IGT) and obese persons with type 2
      diabetes (T2DM). METHODS: 75 g oral glucose tolerance test (OGTT) and Bergman's
      minimal model method of frequently sampled intravenous glucose tolerance test
      (FSIGTT) with reduced sample number (n = 12) were performed on a total of 151
      subjects, 29 normal controls (control group), 44 obese persons with normal
      glucose tolerance (obesity group), 36 obese persons with IGT (IGT group), and 42
      T2DMT patients (T2DM group) to determine the acute insulin response to glucose
      (AIRg), insulin sensitivity index (S(I)), and glucose effectiveness (S(G)). The
      disposition index (DI, AIRg X S(I)) was calculated to determine whether AIRg was
      adequate to compensate for insulin resistance. RESULTS: The S(I) value of the
      control group was significantly higher than those of the obesity, IGT, and T2DM
      groups (all P < 0.01), without significant difference among the latter three
      groups. The S(G) value of the control group was not significantly different from
      that of the obesity group, but significantly higher than those of the IGT and
      T2DM groups (both P < 0.01), without significant difference any 2 groups from the
      latter two groups. The AIRg of the normal group was similar to that of the IGT
      group (2.61 mU x L(-1) x min(-1) +/- 0.13 mU.L(-1) x min(-1) vs 2.56 mU x L(-1) x
      min(-1) +/- 0.25 mU x L(-1) x min(-1)), and significantly lower than that of the
      obesity group (3.02 mU x L(-1) x min(-1) +/- 0.27 mU x L(-1) x min(-1), P < 0.01)
      and higher than that of the T2DM group (1.54 mU x L(-1) x min(-1) +/- 0.55 mU x
      L(-1) x min(-1), P < 0.01). The value of DI was gradually decreased from the
      sequence of the groups of control, obesity, IGT, and T2DM (3.16 +/- 0.31, 2.65 +/
      0.50, 1.67 +/- 0.54), with significant differences between any two groups (all P
      < 0.01). Multiple regression analyses with S(I) and AIRg as dependent variables
      showed that S(I) was negatively correlated with BMI, 2 h glucose level in OGTT, 2
      h insulin, triglyceride, and cholesterol (r(2) = 0.589, P < 0.001), and AIRg was
      positively correlated with BMI, S(G), fasting insulin, and 2 h insulin level and
      negatively correlated with 2 h glucose, and age (r(2) = 0.515, P < 0.001).
      CONCLUSION: Obese patients with different glucose tolerance have similar degrees
      of insulin resistance. Acute insulin response is increased in obesity group to
      compensate for the insulin resistance. Although the acute insulin response in the
      IGT group is similar to that in the control group, however, the compensation of
      islet beta cells in the IGT group is significantly decreased as compared with
      that in the obesity group, leading to glucose intolerance. There is a severe
      deficiency of acute insulin response to glucose in T2DM group.

PMID- 14703430
TI  - [The clinical characteristics and its relationship with metabolic syndrome in
      elderly subjects with impaired glucose regulation].
AB  - OBJECTIVE: To study the clinical characteristics of impaired glucose regulation
      (IGR) in elderly subjects and its relationship with metabolic syndrome (MS).
      METHODS: The exploration of IGR in 2 810 Chongqing citizens over 40 years old was
      done by OGTT in a cross-section study. Normal glucose tolerance (NGT), IGR and
      diabetes (DM) were grouped based on the1999 diagnosis standard of WHO. IGR was
      composed of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and
      both of which. RESULTS: The prevalence of IGR was 18.11%, among which IGT
      (85.27%). Compared with the NGT group, the IGR group had higher age, body mass
      index (BMI), blood pressure, triglyceride (TG), total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-c) and HOMA-IR, lower high density
      lipoprotein cholesterol (HDL-c) and HOMA-B. The IGR group had lower blood
      pressure, TG and HOMA-IR, and higher HOMA-B than the DM group. When each subgroup
      of IGR was compared with each other, both IFG plus IGT subgroup and IFG subgroup
      had higher BMI and HOMA-IR, and lower HOMA-B than IGT subgroup. The prevalences
      of hypertension, lipid disorder, obesity/overweight, and microalbuminuria in each
      subgroup of IGR were statistically higher than that of the NGT group. The
      prevalence of MS in the IFG plus IGT subgroup was higher than that of the IGT
      subgroup. CONCLUSIONS: The incidence of IGR was high in elderly people over 40
      years old in local district of Chongqing city. There were various metabolic
      disorders in the subgroups of IGR. The IFG plus IGT and IFG group had higher BMI,
      hypertension, microalbuminuria and HOMA-IR, but lower HOMA-B than the IGT group.

PMID- 14703431
TI  - [Synergetic role of CD3epsilon and 5-fluorouracil in T Lymphocyte apoptosis and
      P53 expression].
AB  - OBJECTIVE: To investigate the relationship between apoptosis induced by
      CD3epsilon and 5-fluorouracil (5-FU), and study the P53 expression in the
      apoptosis process provide a novel insight and useful information of the apoptosis
      signaling pathway induced by CD3epsilon and/or 5-FU, and an important implication
      for the treatment of T-lymphocyte leukemia. METHODS: The viabilities of Jurkat T
      lymphocytes (JK), TJK [JK with over-expression of the CD8epsilon chimeria
      molecule] and T3JK [JK with over-expression of the CD8epsilon (Y170F/Y181F)
      mutation molecule] cells were cultured and treated with pre-coated anti-CD8 mAb
      (200 micro g/ml) and/or 5-FU (2.5 micro g/ml) were detected with MTS assay and
      the apoptosis percentages were calculated. Western blot was used to detect P53
      expression. To confirm the role of P53 in 5-FU-treated T lymphocytes, pCMV-p53
      plasmid with wild type or mutant p53 were co-transfected transiently with pEGFP
      c1 into TJK and T3JK cells, respectively. RESULTS: CD3epsilon or 5-FU induced
      apoptosis of TJK with increase of P53 expression. Co-treatment with CD3epsilon
      specific antibody and 5-FU elevated the apoptotic rates and P53 expression in TJK
      cells remarkably. The cells transfected with wild-type p53 exhibited more
      sensitivity to 5-FU than that transfected with mutant p53. CONCLUSION: Co
      treatment of CD3epsilon and 5-FU increases the apoptosis and p53 expression,
      suggesting that there is a synergetic role of CD3epsilon and 5-FU on T
      lymphocytes.

PMID- 14703432
TI  - [Adenovirus-mediated CTLA4-FasL gene transfer induces long-term survival of
      cardiac allograft in rats].
AB  - OBJECTIVE: To investigate the potential of exogenously expressed CTLA4-FasL in
      inducing transplantation tolerance using rat cardiac graft model and its related
      mechanisms. METHODS: The heart allograft of DA rat was placed in the abdomen of
      LEW rat, and adenoviruses containing CTLA4-FasL gene (AdCTLA4-FasL) adenovirus
      containing CTLA4Ig, and AdEGPP were infused at a dose of 5 x 10(9) pfu/ml via
      portal vein in different recipients respectively immediately after the operation.
      DA-->LEW cardiac graft controls and syngeneic LEW-LEW cardiac graft controls were
      used. The survival of cardiac allografts was monitored by daily palpation. The
      total cessation of beating was defined as rejection and was confirmed by
      histology. The serum level of CTLA4-FasL was measured via ELISA. The tolerance
      mechanisms were investigated with adoptive transfer, mixed lymphocyte reaction
      (MLR), IL-2 reverse experiment, determinations of frequencies of HTLp and CTLp,
      and analysis of the polarization of TH1/TH2 type cytokines using RT-PCR. RESULTS:
      The survival of DA allografts were prolonged significantly in LEW recipients
      receiving AdCTLA4-FasL with a mean survival time of 71.0 +/- 23.7 d (n = 6),
      significantly longer than those of the untreated recipients (5.7 +/- 0.5 d, n =
      6), AdEGFP-treated recipients (5.2 +/- 0.4 d, n = 6) and AdCTLA4Ig-treated
      recipients (45.7 +/- 12.4 d, n = 6) (call P < 0.05). Prolonged expression of
      serum CTLA4-FasL was shown in AdCTLA4-FasL-treated rats. Splenocytes of LEW
      recipients with long-term surviving cardiac allograft displayed donor-specific
      hyporesponsiveness, which could not be reversed in the presence of exogenous
      added IL-2 in MLR. Frequencies of HTLp and CTLp were significantly reduced. The
      polarization of TH1/TH2 type cytokines was not shown. CONCLUSION: Adenovirus
      mediated CTLA4-FasL gene transfer renders prolonged therapeutic expression of
      CTLA4-FasL in LEW recipient rats, leading to long-term survival of cardiac
      allografts. The induced tolerance is donor-specific, and may result from
      regulatory T cells and the deletion of alloreactive T cells. However, T cell
      anergy and the deviation of TH1/TH2 type cytokines may not be the involved
      mechanism, at least when tested.

PMID- 14703433
TI  - [Proliferation and differentiation of neural stem cells after cerebral
      infarction: an experimental study of adult rats].
AB  - OBJECTIVE: To investigate the proliferation and differentiation of neural stem
      cells after cerebral infarction(CI) in adult rats. METHODS: CI animal model was
      made by ligating the common carotid artery and external carotid artery and
      inserting a piece of nylon thread into the internal carotid artery among 100 male
      Wistar rats. Then the rats were randomly divided into 5 groups: group of I day
      after brain infarction (n = 20), group of 3 days after brain infarction (n = 20),
      group of 7 days after brain infarction (n = 20), group of 14 days after brain
      infarction (n = 20), and group of 28 days after brain infarction (n = 20). Twelve
      rats undergoing sham operation with a piece of nylon thread inserted only into
      the common carotid artery were used as controls. The rats were killed at
      different time points and their brains were taken out. The expression of
      bromodeoxyuridine (BrdU) and Musashil (both used to mark the dividing neural stem
      cells), and of glial fibrillary acidic protein (GFAP) and neuronal nuclear
      antigen (NeuN) (both used to mark the differentiating neural stem cells) were
      determined by immunohistochemistry and immunofluorescence staining. RESULTS: In
      the normal brain tissues, only a small amount of BrdU(+) cells were found in the
      hippocampus. One day after CI the number of BrdU(+) cells began to increase in
      the hippocampus at the CI side (P < 0.05), peaked 7 days after CI with a number 6
      times that at the normal side, began to decrease 14 days after, and almost
      reached normal 28 days after. The number of BrdU(+)/Musashil(+) cells began to
      increase 1 day after CI (P < 0.05), peaked 7 days after, began to decrease 14
      days after, and almost reached normal 28 days after. The number of
      BrdU(+)/GFAP(+) cells at the CI side remained almost unchanged after CI. The
      number of BrdU(+)/NeuN(+) cells began to increase 14 days after CI (P < 0.05) and
      peaked 38 days after. CONCLUSION: Cerebral infarction stimulates the
      proliferation of inherent neural stem cells and most proliferated neural stem
      cells differentiate into neurons.

PMID- 14703434
TI  - [EGF/PI3K signaling pathway regulates the expression of osteopontin in liver
      cancer HepG2 cells].
AB  - OBJECTIVE: To investigate the effect of epidermal growth factor (EGF) on the
      expression of osteopontin (OPN) in liver cancer HepG2 cells. METHODS: Human liver
      caner cells of HepG2 line were cultured in medium without bovine serum. EGF was
      added. Another cells were pretreated with specific phosphatidylinositol 3 (PI3)
      inhibitor Wortmannin and then added with EGF. HepG2 cell were collected. RNase
      prote4ction assay and Western blotting were used to examine the expression of OPN
      in the HepG2 cells. RESULTS: HepG2 cells cultured in the bovine serum free medium
      expressed very low level of OPN. EGF increased the expression of OPN mRNA and
      protein in a dose- and time-dependent manners. Pretreatment of Wortmannin
      significantly reduced the EGF-induced OPN expression. CONCLUSION: EGF increases
      the OPN expression, possibly through PI3 signaling pathway. It is possible to
      block the synthesis of OPN through manipulating several target genes, thus
      inhibiting the metastasis of liver cancer.

PMID- 14703435
TI  - [Induction of apoptosis in prostate cancer cell line PC-3 by BBSKE, a novel
      organoselenium compound, and its effect in vivo].
AB  - OBJECTIVE: To investigate the effects of BBSKE (1,2-[bis (1,2-benzisoselenazolone
      3 (2H)-ketone)]ethane), a novel organoselenium compound, on the proliferation and
      apoptosis of the prostate cancer cell line PC-3, and to study its effect on the
      growth of prostate cancer in vivo. METHODS: Prostate cancer cells of the cell
      line PC-3 was cultivated in media with different concentrations of BBSKE and
      cisplatin. The inhibition of proliferation was measured by colorimetric MTT
      assay. The morphologic changes were observed by fluorescence microscopy, DNA
      fragmentation was visualized by agarose gel electrophoresis, and the DNA
      degradation was determined by flow cytometry. Western blot analysis was used to
      identify the expression of bcl-2 and bax. The activity of caspase-3 was
      determined by a micro-ELISA reader. Mouse prostate cancer cells of the TRAMP-C2
      line were cultured and then injected subcutaneously into 2 male C57BL/6 mice to
      establish the animal model. Then the 2 mice were killed to collect the cancer
      cells. Twenty-four mice were injected intraperitoneally with single cell
      suspension of TRAMP-C2 cell and then divided into 3 groups of 8 mice undergoing
      intraperitoneal injection for 7 days: BBSKE group (BBSKE was administered at the
      dosage of 25mg/kg/day), cisplatin group (cisplatin 2mg/kg/d was injected), and
      control group (pure solvent was injected). Three weeks after the mice were killed
      and the tumors were taken out to calculate the inhibition rate. RESULTS: BBSKE
      inhibited the growth of the PC-3 cells dosage-dependently with a value of IC(50)
      of 17.90 micro mol/L after a 48 h exposure, higher than that in the case of
      cisplatin (15.00 micro mol/L). After exposure of PC-3 cells to BBSKE at the
      dosage of 20 micro mol/L for 48 hours the apoptosis rate was 26.32%,
      significantly higher than that of the control group (1.75%, P < 0.01). The
      expression of bcl-2 was decreased and the expression of bax remained almost
      unchanged along with the increase of BBSKE concentration. The activity of caspase
      3 in the subgroup of BBSKE of the concentration of 5 micro mol/L remained almost
      unchanged, and was increased to 3.65 +/- 0.57 and 4.39 +/- 1.01 respectively in
      the BBSKE 10 micro mol/L and 20 micro mol/L subgroups, both significantly higher
      than that of the control group (both P < 0.05). In the in vivo experiment, the
      growth of tumor was significantly inhibited by BBSKE with an inhibition rate of
      40% and the inhibition rate of the cisplatin group was 48%. CONCLUSION: The novel
      organoselenium BBSKE inhibits the proliferation of PC-3 cell and promote its
      apoptosis, probably through downregulating the expression of bcl-2 and the
      activity of caspase-3. BBSKE also inhibits the growth of prostate cancer in vivo.

PMID- 14703436
TI  - [Downregulation of the pigment epithelium derived factor by hypoxia and elevated
      glucose concentration in cultured human retinal pigment epithelial cells].
AB  - OBJECTIVE: To explore the effect of hypoxia and high glucose concentration on the
      production and secretion of vascular endothelial growth factor (VEGF) and pigment
      epithelium derived factor (PEDF), an antiangiogenesis factor, in the cultured
      human retinal pigment epithelium (RPE) cells. METHODS: Human RPE cells were
      cultured under normoxic or hypoxic (1% O(2)) condition with or without (25
      mmol/L) glucose. RT-PCR and real-time quantificaton analysis were used to examine
      the expression of VEGF and of PEDF mRNAs. Western blot analysis was used to
      measure the levels of VEGF and PEDF proteins. RESULTS: The expression of VEGF
      mRNA in RPE cells under hypoxic condition for 12 hours was 2.6 times that under
      the normoxic condition (P = 0.001), and the expression of PEDF mRNA was only 0.77
      time that of the controls (P = 0.251). Under hypoxic condition with high
      concentration of glucose the expression of VEGF mRNA in RPE cells was 3.8 times
      that under the normoxic condition (P < 0.001), and the expression of PEDF mRNA
      was further decreased (only 0.23 time that of the controls, P = 0.02). The
      expression levels of VEGF protein under hypoxic condition with and without
      glucose were 1.69 and 1.27 times respectively those under the normoxic condition
      (P < 0.0001 and P = 0.004). The expression level of PEDF protein under hypoxic
      condition with glucose was 0.49 time that under the normoxic condition (P <
      0.0001) and the expression level of PEDF protein under hypoxic condition without
      glucose was 0.92 time that under the normoxic condition (P = 0.114). CONCLUSION:
      Hypoxia indirectly influence the downregulation of PEDF and high concentration of
      glucose directly downregulates the expression of PEDF and increases the
      expression of VEGF simultaneously, thus supporting the concept that hyperglycemia
      is one of the most dangerous consequences of diabetes-associated "glucose
      toxicity" in vivo.

PMID- 14703437
TI  - [Observation of bone marrow mesenchymal stem cells after subretinally
      transplanted into laser-injured rat retina].
AB  - OBJECTIVE: Bone marrow mesenchymal stem cells (MSCs) develop into hematopoietic
      and mesenchymal lineages but have not been known to participate in production of
      retina. Eye was known as an immunologically privileged organ. Because of its
      special structure, it's difficult for blood cells to enter retina. This article
      is to trace bone marrow mesenchymal stem cell (MSCs) after subretinally
      transplanted into Nd: YAG laser-injured rat retinal without in vitro
      differentiation induction. METHOD: 4', 6-diamidino-2-phenylindole (DAPI)-labeled
      MSCs were used to trace the change of MSCs after transplantation on day 10, 20,
      35 and 50. The sequenced sections were used for Immunohistochemistry
      identification for neuronal nuclei (NeuN), neuron specific enolase (NSE), glial
      fibrillary acidic protein (GFAP) and pancytokeratin (CK). Electroretinogram (ERG)
      b waves were recorded for each eye of the laser injured group, the laser injured
      transplanted group and the laser injured with saline injection control group
      before, right after or at every end of 1 to 7 weeks. RESULTS: On day 10, the DAPI
      positive cells were mainly crowded around the transplanted site. On day 20 the
      positive area enlarged and scattered into RPE layer, photoreceptor layer, bipolar
      layer and ganglion cell layer. Then the positive area enlarged more widely on day
      35 and more cells could be found migrate to the lesion site. The positive area
      didn't enlarge much on day 50 than on day 35. No formation of rosettes was found
      during the observation. But the expression of NeuN, NSE, GFAP and CK was not
      uniform as the normal retina. Cell proliferation was still found. But HE staining
      showed that the lesion in the transplanted group was better than that of the
      control group. Correspondingly ERG b-wave value at week 5 was higher than the
      control group. CONCLUSION: From these cells, a proportion of the cells
      regenerated from bone marrow can be differentiated into retina in vivo. Although
      the MSCs-derived cells could not precisely express neuro-like proteins, they
      could help recover lesion and ERG b-wave value.

PMID- 14703438
TI  - [Changes of interleukin-6 and Janus kinases in rats with hypoxic pulmonary
      hypertension].
AB  - OBJECTIVE: To investigate the expressions of interleukin 6 (IL-6) and Janus
      kinases (JAKs) in rats with hypoxia induced pulmonary hypertension (HPH).
      METHODS: Sixty male Wistar rats were randomized into 5 groups with 12 animals in
      each: a one-week hypoxic group (H(1) group), a two-week hypoxic group (H(2)
      group), a three-week hypoxic group (H(3) group), a four-week hypoxic group (H(4)
      group), a normal oxygen group (N group). The rat model of HPH was replicated in
      normal baric hypoxic cabin. The levels of IL-6 and JAKs mRNA were measured by
      using reverse transcription-polymerase chain reaction (RT-PCR); The expression of
      JAKs protein and cell morphologic changes were observed by immunohistochemistry.
      RESULTS: (1) The levels of IL-6 mRNA in H(1) (1.67 +/- 0.09), H(2) (2.26 +/-
      0.12) and H(3) (1.55 +/- 0.11) groups were significantly higher than that in N
      group (1.20 +/- 0.11, all P < 0.01). The levels of JAK1 mRNA in H(1) (2.11 +/-
      0.09), H(2) (2.85 +/- 0.12) and H(3) (2.36 +/- 0.13) groups were significantly
      higher than that in N group (1.62 +/- 0.10, all P < 0.01); The levels of JAK2
      mRNA in H(1) (1.41 +/- 0.07), H(2) (2.02 +/- 0.13) and H(3) (1.36 +/- 0.09)
      groups were significantly higher than that in N group (1.01 +/- 0.09, all P <
      0.01); The levels of JAK3 mRNA in H(1) (0.86 +/- 0.11), H(2) (1.45 +/- 0.10) and
      H(3) (0.91 +/- 0.13) groups were significantly higher than that in N group (0.55
      +/- 0.08, all P < 0.01). The levels of TYK2 mRNA in H(1) (1.36 +/- 0.10), H(2)
      (1.76 +/- 0.11) groups were significantly higher than that in N group (0.57 +/-
      0.07, all P < 0.01). The levels of IL-6 and JAKs mRNA in H(2) group were
      significantly higher than those in H(1) and H(3) groups (all P < 0.01). (2)
      Histochemical staining of JAK1 and JAK3 in H(3) group showed yellow cytoplasm of
      alveolar wall cells, bronchial wall cells and small blood wall cells; The active
      protein contents of JAK1 (5.36 +/- 0.32) and JAK3 (4.88 +/- 0.29) were markedly
      increased as compared with N group (1.52 +/- 0.18, 1.22 +/- 0.09, respectively;
      all P < 0.01) by TIGER image analysis method. CONCLUSIONS: The levels of IL-6,
      JAKs mRNA and protein can increase in pulmonary tissues of rats with HPH. It
      suggests that IL-6/JAKs pathway may take part in the pathogenesis of HPH.

PMID- 14703439
TI  - [Effect of tumor necrosis factor-alpha and interleukin-1beta on bovine pulmonary
      arterial endothelial cell apoptosis].
AB  - OBJECTIVE: To investigate the effect of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta) on apoptosis of bovine pulmonary arterial
      endothelial cells (BPEC). METHODS: BPECs were incubated with TNF-alpha, IL-1beta
      or the combination of TNF-alpha and IL-1beta. BEPCs were also pretreated with TNF
      alpha monoclonal antibody or Ac-DEVD-CHO (caspase-3 inhibitor), and followed by
      incubation with TNF-alpha. The apoptotic rate was measured by flow cytometry
      (Annexin V-FITC and PI staining). RESULTS: (1) TNF-alpha induced apoptosis in a
      dose-dependent manner after a 24 h incubation. With the increase of the TNF-alpha
      (500, 1,000, 2,000 U/ml respectively), the BPEC apoptotic rate [(8.21 +/- 0.70)%,
      (9.63 +/- 0.71)%, (17.43 +/- 1.99)%, respectively] was significantly higher than
      that of the control group [(3.09 +/- 0.08)%, P < 0.05]. (2) TNF-alpha induced
      apoptosis was time dependent. After incubated with TNF-alpha 2,000 U/ml, the BPEC
      apoptotic rate [(6.72 +/- 0.38)%, (7.72 +/- 1.66)%, (12.95 +/- 0.32)%, (17.70 +/-
      1.79)%, P < 0.05] increased significantly with time [6, 12, 24, 36 h,
      respectively] of TNF-alpha incubation. (3) The BPEC apoptotic rate of anti-TNF
      alpha monoclonal antibody group [(7.78 +/- 0.21)%] or the Ac-DEVD-CHO group
      [(7.32 +/- 0.11)%] was significantly higher than the TNF-alpha group alone
      [(10.59 +/- 0.49)%, P < 0.01], but the combination of TNF-alpha and IL-1beta
      group had no such significant effect (P > 0.05). CONCLUSIONS: It is TNF-alpha but
      not IL-1beta that induces pulmonary arterial endothelial cell apoptosis in acute
      lung injury (ALI). There is no synergistic effect between IL-1beta and TNF-alpha
      in the induction of BPEC apoptosis.

PMID- 14703440
TI  - [A study on the role of vascular endothelial growth factor in emphysema of rat
      caused by smog exposure].
AB  - OBJECTIVE: To explore the role of vascular endothelial growth factor (VEGF) in
      emphysema of rat caused by smog exposure. METHODS: Thirty-six 12-week male rats
      were randomly divided into 2 groups: a smog exposure group (S group), and a
      normal control group (N group). S group rats were randomly subdivided into 3
      groups: S(1) group, S(2) group, S(3) group, which were exposed to smog for 2
      weeks, 4 weeks, 8 weeks, respectively; N group rats were randomly subdivided into
      3 groups: N(1) group, N(2) group, N(3) group, which were raised in normal oxygen
      condition for 0 week, 4 weeks, 8 weeks, respectively. The expressions of VEGF
      mRNA and VEGF protein and kinase-insert domain containing receptor (KDR) protein
      were determined by reverse transcription-polymerase chain reaction (RT-PCR) and
      modified SABC immunohistochemistry assay separately. The pathological change in
      smog exposure rat lung was determined by HE staining. MLI and MAN were determined
      as an index of emphysema. Variance analysis, nonparametric analysis and correlate
      analysis were conducted in SPSS 10.0. RESULTS: (1) There were airway inflammation
      in S group rat lungs, and an early-emphysema-like change in S(3) group rat lungs:
      MAN in S(3) group was significantly decreased compared with N(3) group, MLI in
      S(3) group was significantly increased compared with N(3) group (P < 0.05). (2)
      VEGF189 mRNA in lung and VEGF protein in alveolar and bronchial epithelium of
      rats in S(1) group were significantly lower than those in N(1) group (P < 0.01);
      VEGF189 mRNA, VEGF165 mRNA and VEGF121 mRNA of lung tissue and VEGF protein in
      alveolar and bronchial epithelium of rats in S(2) group were significantly lower
      than those in N(2) group (P < 0.01), too; VEGF protein in alveolar and bronchial
      epithelium and KDR expression in pulmonary vascular endothelium of rats in S(3)
      group was lower than that in N(3) group (P < 0.01, P < 0.01, P < 0.05), but VEGF
      mRNA have no difference (P > 0.05). (3) VEGF protein expression in alveolar
      epithelium and bronchial epithelium had a positive correlation with MAN (r =
      0.43, r = 0.37, P < 0.05) and an inverse correlation with MLI (r = -0.42, r = 
      0.37, P < 0.05). CONCLUSIONS: Smog exposure decrease the expression of VEGF and
      KDR in rat lung. VEGF might involve in the pathology of emphysema caused by smog
      exposure.

PMID- 14703441
TI  - [Etiological diagnosis of chronic cough with unknown causes].
AB  - OBJECTIVE: To explore the spectrum and frequency of causes for chronic cough in
      Chinese patients. METHODS: 86 patients with chronic cough were enrolled in the
      study. The diagnostic procedure was based on the anatomical protocol for
      diagnosing chronic cough designed by Irwin, and additional cytological assay was
      performed for sputum induced by hypertonic saline aerosol inhalation. The
      efficacy of therapy specific to the diagnosis was evaluated. RESULTS: Definite
      diagnosis was made in 77 (89.5%) out of the 86 patients with chronic cough. The
      most common causes included cough variant asthma (CVA) (24/86, 27.9%), postnasal
      drip syndrome (PNDs) (22/86, 25.6%), eosinophilic bronchitis (EB) (13/86, 15.1%),
      and gastroesophageal reflux (GER) (12/86, 14.0%). After active management based
      on the diagnosis, cough improved in 72 patients (93.5%). CONCLUSIONS: In addition
      to CVA, PNDs and GER, eosinophilic bronchitis is also an important cause of
      chronic cough. A positive response to the specific therapy is essential to a
      definite diagnosis.

PMID- 14703442
TI  - [Relationships between melatonin and cortisol and the status of disease in
      patients with bronchial asthma].
AB  - OBJECTIVE: The aim of the study was to elucidate the interaction and clinical
      significance between melatonin and cortisol and the status of disease in patients
      with bronchial asthma. METHODS: Ten mild persistent and 10 moderate-to-severe
      persistent asthma patients were recruited to participate in the study. Fifteen
      normal subjects served as contrds Salivary free melatonin and cortisol were
      measured simultaneously by radioimmunoassay in all subjects, and 8 salivary
      samples were collected in a series during a 24-hour period in each subject. The
      intensity of light was restricted to natural light at room during the daytime and
      less than 50 lux at night. RESULTS: The results showed that salivary free
      melatonin levels were significantly lower in mild (15.5 +/- 5.3) micro g/L and
      moderate-to-severe (7.1 +/- 2.5) micro g/L persistent asthma patients as compared
      to control subjects (28.9 +/- 8.7) micro g/L (F = 4.47, P < 0.05; F = 7.61, P <
      0.01, respectively). The results also showed that salivary free cortisol levels
      were significantly lower in mild (3.1 +/- 0.5) micro g/L and moderate-to-severe
      (4.2 +/- 0.5) micro g/L persistent asthma patients as compared to control
      subjects (5.9 +/- 0.7) micro g/L (F = 10.45, P < 0.01; F = 5.21, P < 0.05,
      respectively). The amplitude of salivary free cortisol level was reduced in mild
      and moderate-to-severe persistent asthma patients, and salivary cortisol peak
      level was significantly delayed in mild and moderate-to-severe persistent asthma
      patients (P < 0.05, P < 0.01, respectively). There were no significant
      correlations between the salivary free melatonin and cortisol levels in control
      and mild persistent asthma patients (r = 0.174, P = 0.057; r = -0.138, P = 0.221,
      respectively). However, a significant negative correlation was found between the
      salivary free melatonin and cortisol levels in moderate-to-severe persistent
      asthma patients (r = -0.275, P = 0.013). CONCLUSIONS: There were lower salivary
      free melatonin and cortisol levels in asthmatic patients. A significant negative
      correlation was found between melatonin and cortisol levels in moderate-to-severe
      persistent asthma patients. Furthermore, the reciprocal inhibition of melatonin
      and cortisol was closely associated with the status of disease in asthmatic
      patients.

PMID- 14703443
TI  - [Clinical analysis of patients with severe acute respiratory syndrome in Beijing
      area].
AB  - OBJECTIVE: To study the epidemiological, clinical and laboratory characteristics,
      treatment and prognosis of patients with severe acute respiratory syndrome
      (SARS). METHODS: Clinical data from 250 patients with SARS were retrospectively
      analyzed. RESULTS: The age of the patients were 36 +/- 16, 44.0% (n = 110) were
      male, and 56.0% (n = 140) were female. The incubation period was 8 +/- 7 days.
      The most common symptom were fever (100. 0%), cough (72.8%), and fatigue (70.0%).
      27.2% of the patients had decreased white blood cell counts. 64.2% of the
      patients had decreased lymphocytes. 91.4% and 80.6% of the patients had decreased
      CD(4)(+) and CD(8)(+) cell counts, respectively. 162 patients (64.8%) had
      decreased SaO(2). Serum ALT, AST, LDH and CK were elevated in 45.2%, 29.4%,
      42.1%, and 18.3% of the patients respectively. Serum IgG to SARS virus was
      positive in 69.9% of the patients at recovery stage. General combination therapy
      including antibiotics, anti-viral agents, glucocorticoids and immunity-enhancing
      agents, was used. Artificial ventilation was used in 196 patients including 8 for
      whom invasive mechanical ventilation was used Eighty-one (32.4%) were diagnosed
      as having severe type of SARS. 25 patients died of SARS. CONCLUSIONS: SARS is a
      highly communicable disease and mostly affects youth and people in their prime of
      life. It has characteristic clinical manifestations. Combination therapy can be
      very effective for most patients.

PMID- 14703444
TI  - [Evaluation of interleukin-13 in the serum and bronchoalveolar lavage fluid of
      patients with idiopathic pulmonary fibrosis].
AB  - OBJECTIVE: To study the significance of interleukin-13 (IL-13) in peripheral
      blood and bronchoalveolar lavage fluid (BALF) from patients with idiopathic
      pulmonary fibrosis (IPF). METHODS: The level of IL-13 was determined with ELISA
      in the serum and BALF of 17 patients with IPF and 8 subjects with non
      interstitial lung diseases (non-smokers). RESULTS: The level of IL-13 in the BALF
      of the patients with IPF was significantly higher than that in non-interstitial
      lung disease group [(301 +/- 86) ng/L vs. (103 +/- 24) ng/L (P < 0.01)] and was
      higher than that in serum [(178 +/- 36) ng/L vs. (55 +/- 15) ng/L, P < 0.01]. The
      level of IL-13 in the BALF of the patients with IPF was positively correlated
      with the percentage of neutrophils (r = 0.786, P < 0.01). The analysis of
      Spearman correlation showed that the level of IL-13 in the BALF was correlated
      with lung function, PaO(2), and D(LCO) (Spearman correlation coefficient r = 
      0.898, -0.878, -0.874, -0.890, respectively, P < 0.01). CONCLUSION: IL-13 may
      play an important role in the pathogenesis of IPF and be a potential marker of
      IPF activity.

PMID- 14703445
TI  - [Effect and mechanism of arsenic trioxide on chemosensitivity of human lung
      adenocarcinoma cells].
AB  - OBJECTIVE: To study the apoptosis and chemosensitive effect of As(2)O(3) on human
      lung adenocarcinoma cell line A549. METHODS: MTT colorimetric assay,
      immunohistochemical method, flow cytometry and RT-PCR were applied to observe the
      different effects induced by As(2)O(3) with different concentrations on A549
      cells. RESULTS: 1, 2 micro mol/L As(2)O(3) increased Fas expression and inhibited
      the expression of bcl-2, MRP and LRP; G(1) arrest was observed and the cells were
      more sensitive to cisplatin. A549 cells in the presence of 5 micro mol/L
      As(2)O(3) showed growth inhibition and up-regulation of bcl-2, MRP and LRP
      expressions; but their chemosensitivity to cisplatin did not change. CONCLUSION:
      As(2)O(3) in low concentrations can increase the chemosensitivity of A549 cells
      by regulating the expression of apoptosis genes, anti-apoptosis genes and drug
      resistant genes and affecting the cell cycle progress.

PMID- 14703446
TI  - [Application of vascular surgery in the treatment of thoracic neoplasm].
AB  - OBJECTIVE: To investigate superior vena cava (SVC) and anonymous vein resection
      with prosthesis replacement for lung carcinoma and mediastinal tumor, and to
      assess the surgical procedure and prognosis. METHODS: Experimental research:
      Eighteen adult dogs were divided randomly into two groups. Group A (n = 9)
      underwent blocking of the SVC system, and Group B (n = 9) underwent SVC resection
      with prosthesis replacement. The SVC pressure and histological changes of brain
      tissue were measured and evaluated for group A. The histological changes of
      prosthesis were studied in group B. Clinical research: Fifty-six patients with
      thoracic neoplasm were studied, of which 42 were lung carcinoma and 14 were
      mediastinal tumor. Resection of primary lesions and metastatic lymph nodes with
      replacement of SVC system were performed for all patients. Long-term follow-up
      was performed. RESULTS: Experimental research: In Group A, the pressure of SVC
      was higher when both SVC and the azygous vein were blocked as compared to SVC
      blocking only (P < 0.05); hyperemia and edema of brain tissue were not observed
      in two-hour obstruction. The inner face of vascular prosthesis was covered with
      fibrin two months after operation in group B. Vascular endothelial cells were
      found to grow in it, and there was no thrombosis without anticoagulation.
      Clinical research revealed that there was no death associated with the operation
      and there was no early or late obstruction of SVC. The survival rates of the
      patients with lung carcinoma in 1, 3 and 5 years were 84.2% 40.9% and 38.9%
      respectively. The patients with mediastinal tumor were all alive except 1 patient
      who died of metastasis. CONCLUSIONS: Radical resection combined with prosthesis
      replacement of SVC system extends the indications of thoracic neoplasm resection
      and improve the long-term survival rate and living qualities of the patients. It
      may be recommended in the surgical treatment of thoracic tumor.

PMID- 14703447
TI  - [Study of susceptibility and genotype characterization of plasmid-mediated class
      I cephalosporinase in gram-negative bacteria].
AB  - OBJECTIVE: To investigate the susceptibility and genotype characteristics of gram
      negative bacteria producing plasmid-mediated class I cephalosporinase (AmpC beta
      lactamase) epidemic in Southern China. METHODS: A total of 1,187 clinical
      isolates of nonrepetive gram-negative bacteria were collected from different
      cities in Southern China. AmpC beta lactamase producing isolates were identified
      by cefoxitin three-dimensional test, and antimicrobial susceptibility test was
      identified by Kirby-Bauer agar diffusion test; plasmid conjugation, plasmid
      extraction, universal PCR for gene amplication of corresponding group was done,
      and the PCR products were sequenced subsequently. RESULTS: The positive rate of
      cefoxitin three-dimensional test in gram-negative bacteria was 5.9% (70/1,187),
      and the prevalence of plasmid-mediated AmpC beta lactamase was: E. coli: 4.2%
      (19/451), Klebsiella: 4.7% (16/339), Enterobacter: 2.1% (4/190), Alcaligenes:
      5.3% (1/19), Acinetobacter: 2.2% (1/45) and the total positive rate was: 3.5%
      (41/1,187). The susceptibility test showed that compared with the clinical
      isolates, the transconjugations remained resistance to cephamycins and
      ampicillin, and susceptible to cefepime and imipenem. PCR amplication and
      sequencing confirmed them to be bla(DHA-1) gene and bla(ACT-1) gene, and they
      were mainly distributed in Klebsiella and Escherichia. CONCLUSIONS: DHA-1 and ACT
      1 were the most common genotypes in plasmid-mediated AmpC beta-lactamase produced
      by clinical isolates in Southern China. Fourth-generation cephalosporins and
      carbapenems could be better choices for the treatment of infection caused by AmpC
      betalactamase producers.

PMID- 14703448
TI  - [Application of multiplex polymerase chain reaction in rapid identification of
      Mycobacterium bovis BCG].
AB  - OBJECTIVE: To establish a method for the rapid identification of Mycobacterium
      bovis BCG. METHODS: A genomic region designated RD1 was found to be deleted from
      BCG strains, but present in other strains of Mycobacterium bovis and other
      members of the Mycobacterium tuberculosis complex (MTC) including Mycobacterium
      tuberculosis, Mycobacterium africanum, and Mycobacterium microti. With this
      information, a multiplex PCR method, developed to detect the deletion of RD1, was
      used to differentiate BCG strains from other strains of Mycobacterium bovis and
      other members of MTC. RESULTS: RD1 was shown to be absent in 5 BCG vaccine
      strains and 2 BCG strains isolated from an infant who died of systemic
      disseminated infection induced by BCG vaccination, but it was present in 3
      Mycobacterium bovis standard strains, 6 Mycobacterium bovis strains isolated from
      diseased cows, deer or patients with pulmonary tuberculosis and other MTC strains
      including Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains, 48
      Mycobacterium tuberculosis strains isolated from patients with pulmonary
      tuberculosis, and 3 Mycobacterium africanum standard strains. CONCLUSION: The
      multiplex PCR method is simple, rapid, and specific for the identification of BCG
      among strains of MTC, and is applicable in clinical laboratories.

PMID- 14703449
TI  - [A study of the psychological and social factors in patients with pulmonary
      tuberculosis].
AB  - OBJECTIVE: To investigate the mental health and social support in patients with
      tuberculosis. METHODS: Questionnaires were performed in 132 patients with
      tuberculosis and 71 healthy volunteers using Symptom Checklist 90 (SCL-90) and
      Social Support Rating Scale (SSRS). Statistical analyses were processed using
      Student's t test and ANOVA test. RESULTS: Somatization, obsessive-compulsiveness,
      anxiety, phobic anxiety and paranoid ideation, psychotism and the mean of
      positive factors of SCL-90 of the tuberculosis group (1.77 +/- 0.51, 1.63 +/-
      0.50, 1.53 +/- 0.51, 1.33 +/- 0.41, 1.40 +/- 0.45, 1.41 +/- 0.40 and 36.07 +/-
      20.84, respectively) were significantly higher than those of the control group
      (1.30 +/- 0.49, 1.43 +/- 0.49, 1.38 +/- 0.65, 1.24 +/- 0.48, 1.49 +/- 0.69, 1.30
      +/- 0.44 and 24.92 +/- 18.22, respectively) (all P < 0.01). The result of symptom
      self-check differed among patients with different educational levels. The SSRS
      results of subjective and objective supports and total score of social supports
      of the tuberculosis group were 6.90 +/- 2.81, 19.25 +/- 5.62 and 32.96 +/- 7.86,
      respectively, much lower than those of the control group (7.92 +/- 2.57, 21.54 +/
      5.82 and 36.51 +/- 9.01, respectively) (all P < 0.01). Subjective support of
      patients with smear positive tuberculosis was much lower than that of patients
      with smear negative disease (18.15 +/- 5.72 vs. 20.75 +/- 5.78, P < 0.05);
      Subjective support, objective support and total score of social support of the
      unmarried patients (17.19 +/- 4.20, 6.17 +/- 2.18, 30.35 +/- 5.96, respectively)
      were lower than those of the married (20.72 +/- 5.96, 7.66 +/- 3.03, 35.19 +/-
      8.74, respectively) (all P < 0.01). The results of SCL-90 and SSRS had no
      statistical relationship. CONCLUSION: Our results suggest that the disordered
      mental conditions and lower social support in patients with tuberculosis need
      psychosocial interventions in addition to medical care.

PMID- 14703450
TI  - [Comparison of the results and therapies for hepatocellular carcinoma with tumor
      thrombosis in portal vein].
AB  - OBJECTIVE: To compare the clinical effects of different therapies on
      hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT), and to
      study the factors that affected the prognosis. METHODS: One hundred and thirty
      eight HCC with PVTT patients, whose liver function was compensatory and both
      tumor and PVTT could probably be resected together as evaluated by preoperative
      examinations, were divided into four groups: 1. conservative treatment group (n =
      14); 2. chemotherapy group (n = 41); 3. surgical resection group (n = 19); 4.
      surgical resection with postoperative chemotherapy group (n = 64). RESULTS: The
      median survival periods in four groups were 3.5, 7.1, 10.1 and 13.4 months,
      respectively. The half a year-, 1-, 2-, 3-year survival rates in the surgical
      resection with postoperative chemotherapy group were 53.7%, 37.6%, 30.7% and
      14.0%, respectively, which were significantly higher than those of the other
      three groups (P < 0.05). Univariate and multivariate analysis both revealed that
      the number of chemotherapy courses affected the effect of surgical resection.
      CONCLUSIONS: 1. If patients' liver function is compensatory and tumors with PVTT
      can be removed together, exploration should be done. Surgical resection followed
      by postoperative chemotherapy would produce the best clinical result. 2. If
      patients' liver function is permissible, multiple chemotherapeutic courses should
      be given after resection of HCC with PVTT.

PMID- 14703451
TI  - [The causes and prevention of complications of radio frequency ablation treatment
      of primary and secondary liver cancers].
AB  - OBJECTIVE: To sum up causes and the prevention of complications after using the
      radio frequency ablation (RFA) to treat of primary and secondary liver cancers.
      METHODS: The clinical courses of 735 patients, undergoing percutaneous RFA
      treatment for a total of 1780 times were reviewed. The causes of the
      complications occurring after the RFA treatment, and their prevention and
      treatment were evaluated. RESULTS: Eleven complications after RFA treatment were
      found. Postoperative fever, sweating, and local pain were common. Serious
      complications, such as gut perforation, intraabdominal hemorrhage, and
      cardiovascular accident were found in 4 patients, and the mortality was 75%.
      CONCLUSIONS: The RFA treatment is an effective method for the treatment of
      primary and secondary liver tumor. Careful selection of patients, appropriate
      preoperative preparations, proper operative procedures, and suitable
      postoperative care are the key points in preventing the complications.

PMID- 14703452
TI  - [The role of the immunohistochemistry for hMLH1 and hMSH2 with detection of
      microsatellite instability to identify the kindreds with hereditary nonpolyposis
      colorectal cancer].
AB  - OBJECTIVE: To investigate the specificity and sensitivity of the
      immunohistochemistry for hMLH1 and hMSH2 with detection of microsatellite
      instability (MSI) to identify the kindreds with hereditary nonpolyposis
      colorectal cancer and to analyse its value in clinical practice. METHOD:
      Specimens of 16 cases with HNPCC and 16 cases with sporadic colorectal cancer
      were detected by immunostaining with hMLH1 and hMSH2 and MSI was also detected.
      RESULTS: The specificity and sensitivity of the immunohistochemistry for hMLH1
      and hMSH2 were 91.7% and 87.5% respectively. The specificity and sensitivity of
      MSI were 100% and 75.0%. By combining two methods, the specificity and
      sensitivity were 91.7% and 93.8% respectively. CONCLUSIONS: By combination of the
      immunohistochemistry for hMLH1 and hMSH2 and detection of MSI to identify the
      kindreds with HNPCC, the specificity and sensitivity are improved which is better
      than to use either of them alone. And it is very easy and cheap that it can be
      used in clinics.

PMID- 14703453
TI  - [Clinical study of 102 cases of abdominal-anus resection with telescopic
      anastomosis of colon rectal mucosa for lower segment of rectal cancer].
AB  - OBJECTIVE: To investigate the reliability and feasibility of abdominal-anus
      resection with preservation of anal sphincter by telescopic anastomisis of colon
      rectal mucosa for middle-lower segment of rectal cancer. METHODS: A retrospective
      analysis was made for abdominal-anus resection with telescopic anastomosis of
      colon rectal mucosa in 102 cases of middle-lower segment of rectal cancer.
      RESULTS: No anastomotic fistula and anastomotic stenosis occurred in the 102
      cases. The increased defecation was found during early stage of postoperation,
      about 6-12 times per day. But this was easily controlled by antidiarrheal drugs.
      Twelve to 18 weeks later, defecation returned to normal. Follow-up was performed
      in 91 patients, and the follow-up rate was 89.2%. Mean follow-up period was 4.7
      years. Local recurrence rate of the carcinoma was 5.4% (5/91), and hepatic
      metastasis rate was 13.1% (12/91). Three-year survival rate of postoperation was
      86.9% (60/80), and five-year survival rate was 70.7% (29/41). CONCLUSIONS: With
      telescopic anastomosis of colon rectal mucosa, colon stoma can be avoided, and
      anastomotic fistula can be prevented. The operation is safety and effective in
      preservation of anal sphincter for rectal cancer therapy.

PMID- 14703454
TI  - [Treatment of prolapsed hemorrhoids with circular stapler].
AB  - OBJECTIVE: To evaluate the efficacy and safety of circumferential mucosectomy
      procedure for treatment of prolapsed hemorrhoids (PPH). METHODS: From June 2001
      to June 2003, 74 patients (27 men and 47 women) with an average age of 57 years
      (ranging from 31 to 80 years), with prolapsed hemorrhoids III - IV degree
      underwent PPH using a circular stapler. RESULTS: 69 (93.2%) patients were fully
      satisfied with results. Two patients underwent simultaneous rectal polypectomy
      along with PPH hence required analgesic treatment for 5 days. Three patients
      experienced bleeding during or after operation, 1 case bleeding was due to
      ulcerative hemorrhoid, while the bleeding the remaining 2 cases was (bleeding
      about 300 ml) caused by insufficient anastomosis, thus extending operating time
      to 1 hour. The average operation time (70 patients) was 13 minutes (range 10 - 15
      minutes). The mean hospitalization was 3.5 days (2 - 4 days), with exception of 2
      patients lasting 1 week. CONCLUSION: PPH is a safe, effective and rapid method
      for treatment of prolapsed hemorrhoids, The procedure causes minimal pain with
      decreased complications.

PMID- 14703455
TI  - [Expression of matrix metalloproteinase-9 and its complex in the urine of breast
      cancer patients].
AB  - OBJECTIVE: To investigate the expression and clinical significance of matrix
      metalloproteinase-9 and its complex in the urine of the patient with breast
      cancer. METHODS: Using substract gel electrophoresis and western-blot analysis,
      expressions of MMP-9 and MMP-9/NGAL complex in breast cancer (n = 97), breast
      benign (n = 41) and normal (n = 60) were observed. RESULTS: There MMP-9 and MMP
      9/NGAL complex expressions were 76.29% and 64.95% in breast cancer, 46.34% and
      43.90% in breast benign, and 23.33% in normal respectively. The MMP-9 and MMP
      9/NGAL complex expressions were higher in breast cancer than those in breast
      benign and in normal (chi(2) = 7.456, P < 0.01). MMP-9 and MMP-9/NGAL complex
      expressions in urine of breast cancer had not any relationship with tumor size,
      TNM stage, patient age, menopause status as well as ER status, but was correlated
      to lymphatic node status (chi(2) = 5.206, P < 0.05). CONCLUSIONS: MMP-9 and MMP
      9/NGAL complex expressions in urine are significant in estimating lymphatic node
      metastasis in breast cancer and a valuable early prognostic factors and screening
      in breast cancer.

PMID- 14703456
TI  - [Relationship between stenosis of left anterior descending artery and left
      internal mammary artery blood flow].
AB  - OBJECTIVE: To compare the blood flow of left internal mammary artery (LIMA)
      anastomosed to left anterior descending artery (LAD) with variable degree of
      stenosis in off pump coronary artery bypass grafting (OPCAB). METHODS: From
      2000.9 to 2002.12, 167 cases (from a total of 209 OPCAB) were involved in this
      study. According to the degree of stenosis of LAD, all the cases were divided
      into group A (< 75%), group B (75% approximately 95%) and group C (> 95%). Blood
      flow of LIMA, routinely anatomized to LAD was immediately measured after
      anastomosis with transit-time flowmeter (TTFM) and several parameters were
      recorded. RESULTS: The mean blood pressure at measurement was not significantly
      different (P = 0.08). Mean blood flow of group A (11.1 +/- 1.2) ml/min, B (16.3
      +/- 1.6) ml/min and C (28.3 +/- 3.2) ml/min and diastolic flow of group A (26.3
      +/- 2.8) ml/min, group B (34.8 +/- 3.2) ml/min and group C (55.1 +/- 5.3) ml/min,
      were significantly different between every two groups (P < 0.01) and the latter
      was bigger than the former. Systolic blood flow among group A (5.3 +/- 0.7)
      ml/min, group B (4.3 +/- 1.4) ml/min and group C (4.6 +/- 1.3) ml/min were not
      different (P = 0.91). Pulsatility index (PI) of group C (2.75 +/- 0.14) was
      significantly smaller than that of group A (4.36 +/- 0.47) and group B (3.72 +/-
      0.31) (P < 0.01), but PI between groups A and B was of no significant difference
      (P = 0.12). CONCLUSION: Mean and diastolic blood flow of LIMA were closely
      related to the degree of stenosis of LAD. The higher the degree, the bigger the
      blood flow, and the smaller the value of PI. However, systolic blood flow was not
      influenced by the degree of lesion.

PMID- 14703457
TI  - [Clinical analysis of surgical treatment of primary tracheal tumors].
AB  - OBJECTIVE: To summarize the clinical experiences in treating primary tracheal
      tumors by surgery. METHODS: The clinical data concerning 70 surgically treated
      patients between 1968 and 2001 were retrospectively analyzed. RESULTS: There were
      39 sleeve tracheal resections, 13 carinal resections, 10 lateral tracheal wall
      resections, 5 local enucleations, and 1 pneumonectomy. The tumors in 2 patients
      were unresectable. The morbidity rate was 31% (22/70) and operative 30-day
      mortality for resection with primary reconstruction was 8% (4/52). The tumors
      were benign in 14 and malignant in 56 cases. The most common malignant tumors
      were adenoidcystic carcinoma (45%) and squamous cell carcinoma (23%). The cases
      of benign tracheal tumors were followed up for an average of 5.7 years. After
      resection for malignant tumors, the overall 5- and 10-year survival rates were
      64% (21/33) and 54% (14/26), respectively. CONCLUSIONS: Surgical resection is the
      most effective treatment of tracheal tumors. Tracheal resection and
      reconstruction is the treatment of choice for primary tracheal tumors. Benign
      tumors should be resected conservatively with preservation of tracheal
      parenchyma. The reduction of operative complications are key points of good
      surgical results.

PMID- 14703458
TI  - [The surgical management of sacral tumors].
AB  - OBJECTIVE: To investigate the way of sacral tumors surgical treatment. METHODS:
      This retrospective study included 119 cases of sacral tumors surgically treated
      from July, 1996 to December, 2001. The age of patients ranged from 18 to 80 years
      (mean 57 years), including of 72 male and 47 female. Out of the patients, there
      were 52 chordomas, 16 giant cell tumor, 5 neurofibroma, 23 metastases tumors, 9
      myeloma, 2 osteoblastomas, 5 aneurysmal bone cysts, 3 osteosarcomas, 4
      chondrosarcomas. Posterior approach and combined anterior-posterior approach were
      used in 83 and 36 cases respectively. Twenty-nine patients had received surgical
      management at least once and 16 of them had received radiation therapy before
      came to our department. RESULTS: Three patients died on the complication around
      the surgery. Most of the patients with metastases tumor or multiple myeloma died
      1 to 3 years after the surgery. Out of three osteosarcoma patients, 2 died and
      one alive with tumor. Three chondrosarcoma patients died, and one alive with
      tumor. Out of 52 chordoma patients, 3 patients had died of metastatic chordoma, 3
      patients died of many times recurrence. Among the other 46 patients who were stay
      alive, 31 were free from disease with average follow-up time of 42 months. In the
      patients whose sacral nerve roots had been reserved bilaterally at and above S(3)
      level, the sphincter muscle function of bladder and bowl was good. While the
      function of sphincter muscle impaired in 2 patients with nerve roots reserved
      only at and above S(1) level. To manage these 2 patients, indwelling bladder
      catheters were used, but colostomy had not been performed. CONCLUSIONS: Complete
      resection of tumor (radical surgery when possible) is the most effective way to
      manage sacral tumors. Postoperative adjuvant radiation therapy can reduce the
      tumor recurrence rate, but it also can cause troubles that would hinder further
      surgical managements. Even if the tumor is relatively huge and the upper
      resection margin is as high as at S(1) or S(2) level, the tumor can be removed
      successfully by posterior approach and the postoperative complications could be
      accepted. To the patients with aneurysmal cyst or giant cell tumor on sacrum, for
      control bleeding purpose, anterior approach should be performed to ligate the
      bilateral internal iliac artery.

PMID- 14703459
TI  - [Parosteal osteosarcoma: a clinical study of 48 cases].
AB  - OBJECTIVE: To investigate the way of diagnosis and therapy of parosteal
      osteosarcoma. METHODS: A retrospective review was conducted of 48 patients
      treated at our department between June 1964 and December 2001. The average age of
      patients in this study was 29.2 years (13 - 47 years). Thirty-two of the patients
      were female; sixteen were male. The single most common site is the posterior
      aspect of the distal femur (in 36 patients), followed by the femur shaft (in 6
      patients), the proximal tibia (in 2 patients), etc. Nine patients had been
      operated on before referral to our department. RESULTS: The average follow-up
      period from the first operation was 5.2 (0.25 - 24) years. In 36 of the 39
      patients in whom a limb-salvage procedure was performed, a segment of the tumor
      bearing bone was excised along with the tumor, whereas in 3 patients only the
      subadjacent cortex was excised with the tumor. In the limb-sparing group, the
      reconstruction was achieved by means of attenuated tumor bone or allograft in 23
      cases, by endoprosthetic replacement in 9 cases, and by allograft replacement in
      4 cases. The local resections were wide in 35 cases, and marginal in 13 cases.
      After marginal surgery, local recurrence occurred in 5/13 patients, whereas it
      occurred in 3/35 patients treated with wide resection. Pulmonary metastases
      developed in 6 patients, four patients died, and 2 patients are alive with
      disease. There were 4 cases of fractures of bone grafts. Four patients developed
      an infection. Long-term survival rate is 85.8%. For tumors that invaded the
      medullary canal there was no statistical association with local recurrence or
      metastasis. There is statistical significance between surgical margin and local
      recurrence. CONCLUSIONS: Wide surgical excision alone is adequate treatment for
      patients with conventional parosteal osteosarcoma. A tumor-free margin remains
      the critical factor determining overall prognosis. When a marginal excision was
      knowingly done to preserve a major neurovascular bundle, the risk of recurrence
      was less than when it was done to shell-out a presumptively benign lesion.
      Repeated recurrence probably increases the risk of dedifferentiation and thereby
      worsens the prognosis. Recurrent lesions with multiple soft-tissue satellite
      nodules or involvement of the neurovascular structures may however require
      amputation to provide sufficient local control when a wide margin cannot be
      achieved. An individualized resection will be performed in the future probably
      under the help of the advanced technique of image to distinguish the reactive
      zone from the normal tissue precisely.

PMID- 14703460
TI  - [Peri-operative management of fracture in patients with diabetes mellitus].
AB  - OBJECTIVE: To study the characters of the treatment of perioperative period in
      fractures with diabetes mellitus (DM) and the effect of diabetes on the treatment
      of them. METHODS: To retrospectively analyze the clinical data of 97 fracture
      patients with DM (DM group) who accepted operation. Compare the difference of the
      average hospitalized length, medical cost and the incidence of postoperative
      complications with the controls. RESULTS: (1) Insulin dosage was less in
      postoperative period (0.5 +/- 0.2) U.d(-1).kg(-1) than steady period (0.7 +/-
      0.2) U.d(-1).kg(-1) and operative period (0.7 +/- 0.3) U.d(-1).kg(-1), the
      difference is significant (P < 0.05); (2) There were more complications in DM
      group than that in the control group before operation. The fractured patients
      with DM could receive operation after preoperative treatment and improving micro
      circulation; (3) Compared with control group, DM group had longer preoperative
      preparation period of in-hospital duration, and higher in-hospital medical costs;
      (4) There were no significant difference between DM group and control group (P >
      0.05) in postoperative complications and wound healing. CONCLUSIONS: Fractured
      patients with DM should take effective methods to treat complications of DM and
      do adequate preparation for the operation. Rational treatment of preoperative
      complications is very important for preventing postoperative one and guarantee
      operation successful. But the longer of hospitalized length is, the higher of in
      hospital medical costs are.

PMID- 14703461
TI  - [Fluid management and cause of death during shock period in patients with severe
      burns or burns complicated by inhalation injury].
AB  - OBJECTIVE: To explore fluid management and cause of death during shock period in
      severe burns or burns with inhalation injury. METHODS: One hundred and twelve
      patients with severe burns or burn complicated by inhalation injury admitted to
      our hospital from 1991 to 2000 were analyzed. The fluid management and death
      conditions during shock period were discussed. RESULTS: The fluid volume for
      resuscitation could be described as follows: the total fluid volume was 2.2
      ml/(%TBSA.kg) including colloid fluid 0.5 ml/(%TBSA.kg), crystalloid fluid 1
      ml/(%TBSA.kg)and water 0.7 ml/(%TBSA.kg) during first 24 hours. The total fluid
      volume was 1.8 ml/(%TBSA.kg) including colloid fluid 0.4 ml/(%TBSA.kg),
      crystalloid fluid 0.7 ml/(%TBSA.kg) and water 0.7 ml/(%TBSA.kg) during second 24
      hours. There were no difference in fluid management between burns and burns with
      inhalation injury. Seven patients died due to respiratory failure during shock
      period. CONCLUSIONS: Many fluid formula can provide guidance for resuscitation
      and it is very important that early fluid therapy should accord with concrete
      clinical conditions of patients in order to pass smoothly through shock period.
      Early fluid management is not different between burns and burns with inhalation
      injury.

PMID- 14703462
TI  - [Synergistic protective effect of testicular cells expressing Fas ligand and
      cyclosporine A on the survival of islet allografts].
AB  - OBJECTIVE: To explore the synergistic protective effect of co-transplanted
      testicular cells expressing FasL and CsA on survival of islet allografts.
      METHODS: The allogeneic islets and testicular cells were co-transplanted into the
      renal subcapsular space of the diabetic recipients with or without CsA after
      operation. Allografts survival period and the testicular cells or islets function
      were analyzed. RESULTS: The mean survival period of control group was 4.6 +/- 1.1
      days. When CsA was administered after transplantation, the mean survival period
      of islet allografts, (21.8 +/- 4.7) days, was significantly longer than that of
      control group (P < 0.01). When islets were co-transplanted together with 1 x
      10(7) testicular cells (group A), a significant prolongation of graft survival
      was found (more than 57.5 +/- 4.0 days; P < 0.01 vs. control). But if 1 x 10(7)
      testicular cells expressing FasL were cultured with FasL-mAb for 30 minutes
      before co-transplantation (group B), the mean survival period of islet allografts
      (5.8 +/- 2.6 days), was similar to that in control group, but significantly
      shorter than that in group A (P < 0.01). When islets and 1 x 10(5) testicular
      cells were co-transplanted separately into the bilateral renal subcapsular space
      with CsA (group C), the survival of islet allografts was significantly prolonged
      in comparison with control group (more than 55.0 +/- 6.5 days; P < 0.01 vs.
      control), and similar to islets co-transplanted together with 1 x 10(7)
      testicular cells (group A). When islets were co-transplanted separately with 1 x
      10(6) testicular cells without CsA (group D), the mean survival period (11.5 +/-
      3.1 days) was shorter than that in group C, but prolonged in comparison to
      control group (P < 0.05). CONCLUSION: The co-transplanted testicular cells
      expressing FasL with administering CsA post-transplantation can jointly inhibit
      immune rejection of islet allografts by different mechanism and play a systemic
      and synergistic protective role to islet allografts.

PMID- 14703463
TI  - [Experimental study of diode-laser induced thermocoagulation on hepatic tissue
      with scanner fiber tip].
AB  - OBJECTIVE: To seek a safe, efficient, and cost-effective technique for local
      thermo-ablation of hepatic cancer. METHODS: The livers from 16 healthy rabbits
      were thermocoagulated by diode-laser with scanner fiber tip, 6 w for 10 mins. At
      the same time, the temperatures were measured at 0, 5 and 10 mm from laser tip.
      The pre-thermocoagulative liver function was compared with that of 7 days post
      thermocoagulation. The pathologic changes were also observed 1 month after laser
      thermocoagulation. RESULTS: All the rabbits survived and hepatic tissue
      temperatures at 0, 5, 10 mm from laser tip reached 96.39 degrees C +/- 3.97
      degrees C, 60.79 degrees C +/- 6.21 degrees C, 46.10 degrees C +/- 4.58 degrees C
      respectively after 10 minutes of thermocoagulation. There were no significant
      differences in liver function parameters between rabbits of pre-laser
      thermocoagulation and of post-laser thermocoagulation. Thermocoagulated necrosis
      of liver tissue with surrounding fibrosis in a diameter of 26.0 mm was formed.
      Light microscopy revealed coagulative necrosis in the center of the coagulated
      area without surviving hepatic cells. CONCLUSION: The hepatic tissue can be
      coagulated safely and effectively by diode-laser with scanner fibertip, and such
      a technique may provide a new method for the treatment of hepatic carcinoma.

PMID- 14703464
TI  - [Inhibitory effect of dendritic cells induced activated cytotoxicity T lymphocyte
      combined with MAGE-1 nonapeptide on transplanted human hepatocyte carcinoma in
      nude mice].
AB  - OBJECTIVE: To observe the inhibitory effect of dendritic cells (DCs) activated
      cytotoxicity T lymphocyte (CTL) combined with MAGE-1 nonapeptide on transplanted
      human hepatocyte carcinoma (HCC) in nude mice. METHODS: A model of HCC
      transplanted tumor was established by injecting BEL-7402 cell line HCC cells
      subcutaneously on the back of nude mice. Successful transplantation rate was 73%.
      Specific CTLs (1 x 10(6)), which were activated by DCs combined with MAGE-1
      nonapeptide, were injected into the site of transplanted tumor (group A, n = 5).
      Another group of 17 mice were treated with same amounts of different kinds of
      cells, and they were divided into groups B, C, D, E, and F. The growth of tumor
      was observed, and pathological examination was also done. RESULTS: (1) The
      activated lymphocytes induced by DCs combined with MAGE-1 nonapeptide could
      suppress the growth of tumor and reduce the tumor size. In group A, 5/5 mice
      survived for at least two weeks, while the tumors grew rapidly and the majority
      of the mice died within two weeks in other groups (groups B, C, D, E, F) (P <
      0.01). (2) Extensive necrosis and apoptosis were found in transplanted tumors in
      group A. CONCLUSIONS: The DCs combined with MAGE-1 nonapeptide could not only
      inhibit the growth of HCC, but also result in produce death and apoptosis of HCC,
      hence preventing tumor metastasis and recurrence. The mechanism underlying tumor
      immunization resulted from DCs might be enhanced in apoptosis of tumor cells.
      MAGE-1 nonapeptide combined with DCs might be a potential novel tumor vaccine for
      the treatment of HCC.

PMID- 14703465
TI  - [Effects and mechanisms of endotoxin pretreatment on lung of rat in endotoxemia].
AB  - OBJECTIVE: To observe the effects and mechanisms of endotoxin pretreatment on the
      rat lung in endotoxemia. METHODS: Eighty-four male Wistar rats were divided into
      seven groups (each group containing 12 rats): saline control and
      lipopolysaccharide (LPS)-treated 2 h, 4 h, 6 h groups and LPS-pretreated 2 h, 4
      h, 6 h groups. LPS-pretreated rats were administrated with intraperitoneal
      injection of 0.25 mg/kg LPS. After 24 hours, they were injected with 0.5 mg/kg of
      LPS. Saline control and LPS-treated rats received an equivalent amount of saline.
      After 72 hours, LPS-treated and LPS-pretreated rats were intravenously injected
      with 10 mg/kg of LPS. An equivalent amount of saline was injected in the control
      rats. Blood was drawn from the carotid artery in LPS-treated and LPS-pretreated
      rats and sacrificed after intravenous injection of LPS 2, 4, 6 hours. Following
      saline injection of control rats, blood was drawn from the carotid artery after 6
      hours. Arterial blood was drawn for blood gas analysis. The lungs were removed
      for detecting the mRNA levels of intercellular adhesion molecule-1 (ICAM-1) by
      reverse transcription polymerase chain reaction and the protein levels of
      inhibitor kappa B-alpha (I kappa B-alpha) by immunohistochemical staining.
      Bronchoalveolar lavage was performed in the right lung. Cell counts were
      evaluated with a light microscopy. The supernatant of bronchoalveolar lavage
      fluid (BALF) was assayed for the level of protein. The whole lung was weighed and
      the value was used to determine the lung-body index. The tissue was homogenized
      and centrifuged for the determination of myeloperoxidase enzyme (MPO) activity.
      RESULTS: The rats exposed to LPS alone demonstrated an increase in lung-body
      index, protein in BALF, and MPO activity in the lung tissue. In contrast, the
      rats exposed to LPS pretreatment exhibited a significant decrease in lung-body
      index, protein in BALF, and MPO activity. There was a significant decrease in the
      level of arterial bicarbonate in the LPS-treated rats in comparison with saline
      treated and LPS-pretreated animals at 2 hours to 6 hours after LPS
      administration. The decrease of arterial bicarbonate was compensated by alveolar
      hyperventilation in LPS-treated animals, with a significant decrease in partial
      pressure of carbon dioxide. At the same time, partial pressure of oxygen
      decreased significantly compared with saline control animals and LPS-pretreated
      animals. LPS-treated rats showed a significant gradually increase in ICAM-1mRNA
      in the lung in comparison with the saline group. In contrast, ICAM-1mRNA levels
      in rats pretreated with LPS was lower than that in LPS-treated rats. In LPS
      treated animals, LPS caused a decrease of I kappa B-alpha protein expression at 2
      hours, returned to control level at 4 hours, and remained at 6 hours. There was
      no decrease of I kappa B-alpha protein expression in LPS-pretreated animals.
      CONCLUSION: The results in this study showed that administration of a small dose
      of LPS 72 hours before endotoxemia caused a attenuation effect on lung injury,
      which may be correlated to I kappa B-alpha expression induced by LPS
      pretreatment.

PMID- 14703466
TI  - [A preliminary study of maxillary reconstruction using free fibula-flexor
      hallucis longus myofascial flap].
AB  - OBJECTIVE: To analyze the rationale and feasibility of maxillary reconstruction
      using free fibula-flexor hallucis longus myofascial flap. METHODS: Nine
      consecutive cases of maxillary reconstruction using free fibula-flexor hallucis
      longus myofascial flaps from August of 2002 to August of 2003 were reviewed. Data
      concerning the operation included description of maxillary defect, design of the
      fibula flaps, recipient vessel and complications. RESULTS: One flap experienced
      venous thrombosis after operation, and the flap was salvaged after exploration.
      All the flaps survived completely with the overall success rate of 100%, as well
      as the 100% survival of all fibula-flexor hallucis longus myofascial flaps.
      CONCLUSIONS: Maxillary reconstruction using free fibula-flexor hallucis longus
      myofascial flap without skin paddle is feasible and reliable.

PMID- 14703467
TI  - [The effects of smoking on gingival crevicular fluid volume and elastase before
      and after initial periodontal treatment].
AB  - OBJECTIVE: To investigate the relationship between smoking and gingival
      crevicular fluid volume (GCF), level of elastase (EA) in 37 severe periodontitis
      patients before and after 1 month periodontal initial treatment. METHODS: The GCF
      samples were collected from 122 sites in 22 heavy smokers (>or= 20
      cigarettes/day) and 90 sites in 15 non-smokers before and after 1 month
      periodontal initial treatment. There is no difference (P > 0.05) on pocket depth
      between smoking sites (5.6 +/- 1.2) mm and non-smoking sites (5.4 +/- 1.2) mm at
      baseline. The volume of each GCF sample was measured by Periotron 6000 and the
      elastase in GCF were determined by substrate (meosuc-als-als-pro-val-NA) method.
      RESULTS: After non-surgical treatment both GCF volume and elastase level were
      significantly decreased (P < 0.001) in both smokers and non-smokers. But the
      decrease of GCF volume (91 sites, 74.6%) and elastase level (70 sites, 76.1%) in
      smokers were significant lower (P < 0.01) than non-smokers (GCF, 88 sites, 97.8%;
      EA, 56 sites, 93.3%). CONCLUSION: These findings suggest that smoking has effect
      on gingival crevicular fluid volume and elastase level of patients with
      periodontitis.

PMID- 14703468
TI  - [High-resolution electron microscopy of carious dissolution of enamel nano
      crystals].
AB  - OBJECTIVES: To investigate the carious dissolution mechanism of enamel apatite
      nano-crystals at lattice fringe level and the possible correlation between the
      carious dissolution and the appearance of central dark line (CDL) in enamel
      crystals. METHODS: The body of the lesion in incipient enamel caries was observed
      by high resolution transmission electron microscopy (HRTEM, JOEL-2010 operating
      at 200 kv), combined with selected-area argon-ion-beam thinning technique.
      RESULTS: In the body of the lesion, the preferential core dissolution was found
      in most of enamel nano-crystals, whereas the peripheral dissolution of individual
      crystal could be occasionally observed. The initial carious dissolution of
      individual enamel apatite crystal occurred as a number of small electron-lucent
      spots along the central dark line with blurry, bent or disconnected lattice
      fringes. These small electron-lucent spots fused with each other to form large
      electron-lucent areas. Finally the central perforation was frequently seen in the
      crystals. The CDL always appeared in the same place with central perforation in
      carious crystals, which could be seen to extend along the CDL. CONCLUSIONS: The
      initial carious dissolution is directly related to the lattice defects in the
      enamel nano-crystals. The preferential core dissolution can be partly ascribed to
      the CDL, which is presumed to be particularly susceptible area to caries.

PMID- 14703469
TI  - [Speech outcomes in patients of maxillary reconstruction with free fibula
      composite flap].
AB  - OBJECTIVE: To evaluate speech outcomes in patients of maxillary reconstruction
      with free fibula composite flap. METHODS: Speech measurements of 20 patients of
      maxillary reconstruction with free fibula composite flap were collected.
      Palatopharyngeal valve, the symmetry and movement of soft palate, hypernasality
      and nasal emission were examined by nasoendoscopy. At the same time the speech
      intelligibility was measured. RESULTS: No palatopharyngeal valve insufficiency
      was found and all the soft palates had good symmetry and movement. The average
      speech intelligibility was 98.4%. CONCLUSIONS: Free fibula composite flap can
      reconstruct the phonatory structure and support the function of soft palate,
      which can restorate speech function well. It is a good choice for maxillary
      reconstruction.

PMID- 14703470
TI  - [Three dimensional finite element stress analysis on superstructure of the fixed
      bridge supported by tooth-implant].
AB  - OBJECTIVE: To reveal the stress distribution in the superstructure of fixed
      bridge supported by tooth-implant in the process of mastication for improvement
      of denture design. METHODS: The stress distribution and displacement of the
      superstructure were studied and analyzed by means of CT Scan, CAD and three
      dimensional finite element when various loads were applied. RESULTS: (1) The
      stress distribution in abutments under oblique loads at forty-five degrees was
      uneven and the peak value was 4 - 6 times higher than that under vertical loads.
      Stress concentration occurred with significant compressive stress. (2)
      Compressive stress widely distributed in the middle area of occlusal surface of
      pontic, whose peak value under concentrated loads was significantly higher than
      that under disperse loads. The loading direction had no effect on the stress
      concentration. (3) The maximum displacement of implant abutment in medial-distal
      direction was greater than that of the neck of nature tooth. CONCLUSIONS: The
      mechanic complications of superstructure could be prevented by reducing oblique
      loads and concentrated ones. It is certain that the further improvements of curve
      resistance of pontics and press-resistance of abutments are available.

PMID- 14703471
TI  - [Effect of IgY solution on dental plaque].
AB  - OBJECTIVE: To observe the effect of the IgY solution on dental plaque and mutans
      Streptococci in plaque and in saliva. METHODS: A double-blind study was used. 44
      school children at the third grade in test group used the IgY solution for 21
      days; 41 children in control group used the placebo. The plaque index, the plaque
      weight, the level of mutans streptococci in saliva and in plaque were tested for
      all children. RESULTS: The plaque weight in test group was (46.4 +/- 31.2) mg at
      baseline, and (36.6 +/- 25.6) mg at the end of the study (P = 0.007). The IgY
      solution reduced 21.1% plaque weight. Statistically significant differences for
      other indices were not shown in this study. CONCLUSION: The 0.1% IgY solution
      reduces the mass of plaque on the tooth surfaces.

PMID- 14703472
TI  - [Circulating test and analysis of clasp retention].
AB  - OBJECTIVE: To show the trend of the retention change during the circulation of
      the clasp dislodging and inserting, and to discuss the proper depth of the
      undercut for a specific clasp. It is also a basic study for the best designing of
      RPD. METHODS: The Chatillon force measuring instrument was used to record the
      variation of the retention of Co-Cr alloy casting Akers clasp when they were
      dislodging from undercuts of different depths (0.25 mm, 0.50 mm, 0.75 mm) on
      bicuspid and molar. RESULTS: The data was analysed of Correlation and Regression
      by SPSS 10.0 statistic software. The variations of the retention in the
      circulation are obvious from the different teeth and different undercut depths.
      It shows an attenuation trend in circulation (P < 0.01). After 400 times
      dislodging, in bicuspid group, the retention of the clasp used in 0.50 mm
      undercut became less than the one used in 0.25 mm undercut. While the retention
      of the clasp used in 0.75 mm decreases most obviously, it values 0.7670 kg. In
      molar group, the attenuations of the retention at different depths of undercut
      are similar, the retentions of the clasp still rank as, from great to less, 0.75
      mm, 0.50 mm and 0.25 mm, in the depth of undercut. CONCLUSION: the proper depth
      of the undercut for bicuspid is 0.25 mm, and 0.50 mm for molar.

PMID- 14703473
TI  - [Effect of chewing sugar-free gum after sucrose challenge on dental plaque pH in
      situ].
AB  - OBJECTIVE: To evaluate the effect of chewing sugar-free gum after sucrose
      challenge on dental plaque pH in situ. METHODS: 16 healthy volunteers aged 23 -
      32 years were screened as subjects. The pH of 48-hour dental plaque was measured
      using a Beetrode pH microelectrode when subjects chewed Extra sugar-free gum
      after sucrose challenge. RESULTS: Dental plaque pH maintained at resting plaque
      pH when immediately chewed sugar-free gum after sucrose challenge. Chewing sugar
      free gum at 5 min after sucrose challenge, dental plaque pH was raised from 5.59
      (measured at 5 min after sucrose challenge) to 6.98 (measured at 10 min after
      sucrose challenge). CONCLUSIONS: Chewing sugar-free gum after sucrose challenge
      can neutralize organic acid produced by bacteria in dental plaque and rapidly
      rise plaque pH.

PMID- 14703474
TI  - [Infection of human papillomavirus in oral benign epithelial proliferation in
      children].
AB  - OBJECTIVE: To investigate the presence of HPV infection of oral mucosa
      proliferative lesions in children and determine the associations of HPV types
      with oral mucosa lesions in children. METHODS: Immunohistochemical method and in
      situ hybridization techniques were applied to detect human papillomavirus (HPV)
      infection in biopsies taken from clinical lesions in oral mucosa of 30 children.
      RESULTS: The most frequent lesions detected were SCP (66.7%), followed by CA and
      FEH. The HPV viral antigen was present in 73.3% (22/30) of the oral benign
      epithelial proliferative lesions in children. A high frequency HPV was found in
      CA (6/6) and SCP (15/20) by means of IHC. In the ISH positive case, high risk HPV
      16/18 was observed in 77.3% (17/22). CONCLUSION: This study demonstrates a high
      prevalence of HPV infection in children's oral mucosa proliferative lesions, and
      high-risk HPV16/18 are predominant in children's oral mucosa proliferative
      lesions.

PMID- 14703475
TI  - [Expression of homeobox gene Msx-1, Msx-2 and Dlx-2 during murine mandibular
      first molar development].
AB  - OBJECTIVE: To observe the expression of homeobox gene Msx-1, Msx-2 and Dlx-2
      during murine mandibular first molar development. METHODS: The murine heads or
      mandibles on embryonic days 11-18 (E11-18) and postnatal day 1-3 (P1-3) were
      removed, fixed and embedded, 5 micro m serial sections were cut in the coronal
      plane. Msx-1, Msx-2 and Dlx-2 RNA probes were synthesized by in vitro
      transcription and labeled with digoxigenin. Msx-1, Msx-2 and Dlx-2 mRNA
      expression was observed after in situ hybridization. RESULTS: During molar
      development Msx-1 transcripts appeared only in mesenchymal cells, not in
      epithelial cells. Msx-2 and Dlx-2 both expressed in the epithelial and
      mesenchymal cells. At the initiation stage of the molar development Msx-2 and Dlx
      2 had similar expression. At the bud stage (E13-14) Msx-2 mRNA signaling was
      intensive in the enamel organ and slight in the dental mesenchyme; Dlx-2
      signaling was stronger in the dental papilla. At cap stage (E15-16) Msx-2 showed
      prominent mRNA signaling in enamel knot and Dlx-2 was maximal in the dental
      papilla. At the late bell stage (P2-3) Msx-2 transcripts were observed in
      odontoblasts but not labeled in ameloblasts, and Dlx-2 transcripts appeared in
      ameloblasts but no labeling was seen in odontoblasts. CONCLUSIONS: Msx-1, Msx-2
      and Dlx-2 are expressed in various patterns during murine mandibular first molar
      development, suggesting they possibly play a role in the interaction between the
      epithelium and mesenchyme during the molar development.

PMID- 14703476
TI  - [A study of calcitonin gene-related peptide-immunoreactive nerve fibers of rat
      molar pulp during traumatic occlusion and after removal].
AB  - OBJECTIVE: To study the effect of traumatic occlusion on CGRP-immunoreactive
      (CGRP-IR) nerve fibres in rat molar pulp and observe the recovery of CGRP-IR
      nerve fibres after removal of traumatic occlusion. METHODS: To observe
      immunohistochemically the change of CGRP-IR nerve fibres in molar pulp during
      traumatic occlusion and after removal. RESULTS: The increase of number, density
      and morphology of CGRP-IR nerve fibres in traumatic occlusion group was more than
      in control group, however, the changes of CGRP-IR nerve fibres in removal of
      traumatic occlusion group were less than in control group. CONCLUSIONS: The
      changes of CGRP-IR nerve fibres in number, morphology, and density are induced by
      traumatic occlusion in rat molar pulp, however, the nerve fibres recover to
      normal by removal of traumatic occlusion.

PMID- 14703477
TI  - [Colony-stimulating factor-1 receptor in rat dental follicle cells].
AB  - OBJECTIVE: To study localization and expression of CSF-1 receptor protein, in
      order to discover the CSF-1 and IL-1alpha effects on CSF-1 receptor mRNA levels
      and to determine if the autocrine effect is inhibited through the CSF-1 receptor.
      METHODS: Immunolocalization of CSF-1 receptor in the cultured dental follicle
      cells and in mandibles of the post-natal rats from day 1 to 11 were performed.
      The effects of different concentrations of CSF-1, IL-1alpha on CSF-1 receptor
      gene expression were detected by means of RT-PCR. RESULTS: Cultured dental
      follicle cells were immunostained for the CSF-1 receptor. In vivo, immunostaining
      showed that the CSF-1 receptor was present in the dental follicle of the first
      mandibular molar at early post-natally and was either absent or greatly reduced
      by day 11 post-natally. High concentrations of cvCSF-1 reduced the gene
      expression of the CSF-1 receptor. IL-1alpha had no effects on CSF-1 receptor mRNA
      levels. CONCLUSIONS: The expression of CSF-1 receptor reaches a peak early post
      natally in the dental follicle of the first mandibular molar of the rat and then
      subsequently declines. High concentrations of CSF-1 inhibits the expression of
      CSF-1 receptor, IL-1alpha has no effect on the expression of CSF-1 receptor mRNA.

PMID- 14703478
TI  - [The monitoring of cleft lip with or without cleft palate in China: 1996 - 2000].
AB  - OBJECTIVE: To describe the epidemiological features of cleft lip with or without
      cleft palate (CL +/- P) in Chinese perinatals. METHODS: From 1996 through 2000,
      hospital-based cluster sampling method was adopted for collecting data. During
      that period all live or still births with 28 weeks of gestation or more delivered
      in monitoring hospitals were assessed within 7 days after birth. RESULTS: The
      birth prevalence rates of cleft lip (CL) and of cleft lip with cleft palate (CLP)
      were 5.03/10,000, 8.97/10,000 respectively, then the rate of CL +/- P was
      14.0/10,000. The prevalence rates in urban and rural area, in male and female
      births were 13.28/10,000 and 15.57/10,000, 16.06/10,000 and 11.40/10,000
      respectively. Significant difference was found among maternal-age-specific
      prevalence rates, and the highest one was observed in >or= 35 maternal age group.
      87.25% of CL +/- P was isolated forms. No secular trend was found during that
      period. The perinatal fatality rate of CL +/- P was 19.04%, and the rate in
      isolated forms was 12.69%, but the rate in syndromic CL +/- P was as high as
      62.60%. CONCLUSIONS: No decline trend in prevalence rate of CL +/- P was observed
      during 1996 approximately 2000. Compared with prevalence rates of CL +/- P in
      some foreign countries, it was higher in China during same period.

PMID- 14703479
TI  - [Chemosensitivity testing of oral squamous cell carcinomas with teniposide].
AB  - OBJECTIVE: To investigate the antitumor effectiveness of teniposide in oral
      squamous cell carcinomas (OSCC) and to find evidence for using teniposide for
      treatment of patients with OSCC. METHODS: Seventy-five patients with OSCC from
      the School of Stomatology, Shanghai Second medical University during 1999 to 2001
      were evaluated. Tumors were diagnosed pathologically, and drug sensitivity
      tested. The antitumor drugs tested were cisplatin (CDDP) and teniposide (VM-26).
      Fresh drug was diluted in complete medium at fold of five times of peak plasma
      concentration (PPC x 5) achieved by intravenous administration of clinical doses.
      The concentrations were VM-26 60 mg/L, CDDP 15 mg/L. RESULTS: The MTT assay was
      performed in 75 of 81 patients (success rate 92.6%). The clinical stages of the
      75 patients according to the UICC TNM classification of malignant tumors were 28
      with stage IV, 34 with stage III, 11 with stage II and 2 with stage I. The
      pathological grades of the 75 patients according to three step classification
      were 18 with Grade I, 37 with Grade I approximately II and 20 with Grade III. At
      a drug concentration of PPC x 5, the inhibition rates of tumor cells for VM-26
      and CDDP were 63.34% and 24.08%, respectively. The inhibition rates of tumor
      cells for VM-26 were significantly higher than those for CDDP (P < 0.01).
      CONCLUSIONS: The inhibition rates of OSCC cells for VM-26 are significantly
      higher than for CDDP. VM-26 may be the first selected drug for treating patients
      with OSCC.

PMID- 14703480
TI  - [Osteosarcoma of maxillofacial area: a clinicopathological study of 61 cases].
AB  - OBJECTIVE: To study the clinicopathology of osteosarcoma in oral and
      maxillofacial region. METHODS: Clinical, histopathological features of 61 cases
      of osteosarcoma in oral and maxillofacial region were studied. RESULTS: The ratio
      of male to female was 1.26:1, with the mean age 39.8. 32.8% cases were occurred
      in maxilla and 57.4% cases in mandible. Histologically 55.7% were osteoblastic,
      16.4% were chondroblastic and 21.3% were fibroblastic. All tumors presented
      common histological feature that the neoplastic cells produced neoplastic bone.
      The recurrence rate of the tumor was 39.1% and the metastasis rate to lung was
      8.7%. CONCLUSIONS: Oral and maxillofacial osteosarcoma was most frequently
      occurred in mandible. There was no significant difference in patient's gender.
      Patients were about 10 years older than those suffered the tumor in long bone.
      Osteoblastic type was the most commonly occurred histological type. The
      recurrence rate of the tumor was relatively high and the metastasis rate to lung
      was low. It seems that the tumor had good prognosis than osteosarcoma of long
      bone.

PMID- 14703481
TI  - [Effects of L-nitroarginine on the recovery of traumatic facial paralysis].
AB  - OBJECTIVE: To study the effects of constitutive nitric oxide synthase inhibitor L
      nitroarginine on the recovery of traumatic facial paralysis in rats and the
      changes of the expression of cNOS and OX42 in the facial nucleus. METHODS: L
      nitroarginine was intraperitoneally injected into rats and the recovery of facial
      paralysis was observed at different time point. and the changes of cNOS and OX42
      positive neurons were studied in facial nucleus. RESULTS: Treatment of L
      nitroarginine could remarkably inhibit the recovery of traumatic facial
      paralysis. The cNOS immunoactivity was obvious inhibited in facial nucleus, while
      the OX42 immunoactivity was obvious increased. CONCLUSION: Endogenous nitric
      oxide may play an important mediator role on the recovery of traumatic facial
      paralysis.

PMID- 14703482
TI  - [Restoration of deformities caused by complex fracture of the orbit region and
      adjacent cranio-maxillofacial fracture].
AB  - OBJECTIVE: In order to improve the diagnosis and treatment of the complex
      fracture of the orbit region and adjacent cranio-maxillofacial fracture. METHODS:
      73 cases with blowout fracture of the orbit and adjacent cranio-maxillofacial
      fracture in recent years were retrospectively analyzed and comparied with
      different methods of treatment. All cases had undertaken CT examinations.
      RESULTS: The positive rate of the CT examinations with blowout fracture of the
      orbit and adjacent cranio-maxillofacial region were 100%. Operating
      repositioning, rigid fixation and artificial material placement were used to
      treat this kind of deformities. CONCLUSIONS: With the progress of modern
      photographic methods, blowout fracture of the orbit and adjacent cranio
      maxillofacial fracture can be diagnosed clearly and help the operation procedure.
      Operations with reduction, rigid fixation and filling materials can be used to
      restore this kind of fracture and appearance.

PMID- 14703483
TI  - [Mandibular fracture fixed with PDLLA/nano-HA compound plates: an animal study].
AB  - OBJECTIVE: To investigate the applicability of PDLLA/nano-HA compound plates used
      in internal fixation of mandibular fractures. METHODS: Rabbit mandibular fracture
      model was used in this study. Clinical observation, the amount of callus,
      histological observation were studied and compared with PDLLA plates. RESULTS:
      All fractures were fixed rigidly. There was 1 animal experienced local
      inflammation and then forming fistula in the side of PDLLA plate at postoperative
      2 and 3 weeks. No side-effects were found in the side of compound plates. During
      the early stage of bone healing, the quality of callus in the side of compound
      plates was apparently more than that in the other side, and histological study
      showed that the osteoblasts and fibroblasts were more active in the side of
      compound plate in the early healing stage. CONCLUSIONS: PDLLA/nano-HA compound
      plate has a proper degradation time. Compared with PDLLA plates, it is more
      effective and safer when used in mandibular fracture.

PMID- 14703484
TI  - [A factors study of root resorption after orthodontic treatment].
AB  - OBJECTIVE: To investigate the factors relating to root resorption after
      orthodontic treatment. METHODS: 96 cases treated with fixed appliances were
      selected. The panoramic radiographs before and after treatment were examined. The
      relationship between root resorption after treatment (RRAT) and the variables
      including sex, age, extraction or nonextraction approach, tooth location,
      treatment duration and the root resorption before treatment (RRBT) were analyzed
      by multiple variance analysis and stepwise multivariate linear regression
      analyses. RESULTS: (1) There were statistically significant differences in root
      resorption in relation to gender (estimate of RRAT for female: 0.41, that for
      male: 0.34), extraction (estimate of RRAT for the extraction group: 0.43, that
      for non-extraction: 0.31), anterior or posterior teeth (estimate of RRAT for the
      anterior teeth: 0.59, that for the posterior teeth: 0.12). (2) The estimate of
      RRAT for the upper teeth was 0.40, and that for the lower teeth was 0.37. There
      were no statistically significant differences. (3) Using multiple regression
      analysis, age, duration and RRBT were associated with RRAT (R = 0.59, R(2) =
      0.35). CONCLUSIONS: (1) Factors including gender, extraction or not and anterior
      or posterior teeth have influences on the RRAT. More root resorption was found in
      female or extraction cases. Anterior teeth were more susceptible to root
      resorption relative to posterior teeth. (2) Age, treatment duration and RRBT can
      explain approximately 35% of the RRAT. Root resorption aggregated when it was
      present before treatment. The age and treatment duration were lightly related to
      the root resorption.

PMID- 14703485
TI  - [Stress analysis of separators with different specifications].
AB  - OBJECTIVE: To evaluate the shape and structure of different separators affecting
      the mechanical behavior. METHODS: The stress of different separators was analyzed
      by ANSYS software. Various separators were meshed into one-dimensional solid
      elements and the material character parameters were inputted. The loads were
      added gradually. RESULTS: The stress was related to the arm of force and the
      point of force application. CONCLUSIONS: The force applied can be controlled by
      selecting different separators.

PMID- 14703486
TI  - [Rheological properties of photo-polymerized composite resin reinforced with
      retentive filler].
AB  - OBJECTIVE: To determine the rheological properties of the photo-polymerized
      composite resin reinforced with retentive filler (RF) and its rheological
      difference with normal filler (NF) composite resin. METHODS: Rheological
      properties of the composite resins, such as viscosity, shear stress and creep
      compliance, were measured with dynamic stress rheometer at room temperature (25
      degrees C). RESULTS: The viscosity of the composite resin reinforced with RF is
      higher than that of NF composite resin (P < 0.01); at the beginning, the
      viscosity of the former has little change with the rising of shear stress and the
      latter decreases, then the viscosities of the two composite resins increase with
      the rising of shear stress as soon as over 203.18 Pa of shear stress; the creep
      compliance of the composite resin reinforced with RF is significant smaller than
      that of NF composite resin (P < 0.01). CONCLUSIONS: The rheological properties of
      the two composite resins have significant difference, so they have different
      clinical using properties.

PMID- 14703487
TI  - [A pilot study of repair of periodontal bone defects with carbonated phosphate
      bone cement modified with synthesized peptides in dogs].
AB  - OBJECTIVE: To explore the possibility of repairing periodontal defects with
      carbonated calcium phosphate bone cement (CCPBC) modified with synthesized
      peptides. METHODS: Periodontal bone defects in 4 dogs were surgically created and
      then restored directly with hydroxyapatite (HA), Perioglass, CCPBC and CCPBC
      modified with peptides. The results were compared at different levels. RESULTS:
      Bone replacement materials were lost in HA and Perioglass groups. In the HA group
      defects were restored with connective tissue. Perioglass group had only a little
      new bone around materials by alveolar bone. CCPBC could firmly stay in bone
      defects to maintain the space of bone defects even without membrane use. CCPBC
      modified with peptides was superior to HA, Perioglass, and CCPBC, surrounded by a
      great deal of new bone. CONCLUSION: Under limitation of this study, CCPBC
      modified with peptides has some osteoinuctive activity and may have good prospect
      for the clinical application in periodontal defect repair.

PMID- 14703488
TI  - [Bone formation in vitro and in vivo by human bone marrow-derived mesenchymal
      stem cells].
AB  - OBJECTIVE: To culture and study the osteogenic characteristics of human bone
      marrow-derived mesenchymal stem cells (hBMMSCs). METHODS: hBMMSCs were separated
      and cultured from human iliac crest marrow. Growth kinetics of hBMMSCs was
      studied by growth curve. Under the osteoinductive culture, osteogenic
      differentiation of hBMMSCs was tested by alkaline phosphatase (ALP). Osteogenic
      functions of hBMMSCs in vitro and in vivo were also respectively detected by von
      Kossa stain and by transplanting hydroxyapatite/tricalcium phosphate ceramics
      (HA/TCP) with hBMMSCs. RESULTS: hBMMSCs were cultured successfully. The growth
      curve of the second passage of BMMSCs indicated that the time of population
      doublings was about 3.5 days. The results of ALP stain were evident by the
      significant increase in ALP activity after hBMMSCs cultured in osteoinductive
      medium. Some mineralized nodules were detected by von Kossa stain at nineteenth
      day of osteoinductive culture. In vivo assay, histological evalution showed bone
      formation in 3 months after grafts of HA/TCP with hBMMSCs. CONCLUSIONS:
      Osteoinductive solution can induce hBMMSCs to differentiate osteogenetic cell
      lines. Mineralized nodules and bone formation were found in vitro and in vivo
      assay. The results demonstrate that hBMMSCs have the potential for osteogenesis.

PMID- 14703489
TI  - [The apply of Cosmopost ceramic posts in clinic].
AB  - OBJECTIVE: To investigate the manufacture method and the effects of Cosmopost
      ceramic posts, to summarize the indications of Cosmopost ceramic post in clinic.
      METHODS: 228 pieces Cosmopost ceramic posts and cores were made for 96 patients.
      2l7 pieces full ceramic crowns and 8 pieces full ceramic bridgs for Cosmopost
      ceramic posts and cores were made. The fitness of Cosmopost ceramic post were
      checked, and the color of all full ceramic crowns and full ceramic bridgs were
      checked in clinic. The amount of loosening and broken in all restorations were
      checked every year in clinic. follow up 2 - 3 years. RESULTS: 1 Cosmopost ceramic
      post was fracture about 1.5 mm before the full ceramic crown was worn. 227 pieces
      Cosmopost ceramic posts were perfect. All of the full ceramic crowns and bridgs
      for full ceramic posts were excellent in color. No loosening and broken cases
      were checked in 0.5 - 3 years. But the indications of Cosmopost ceramic posts
      were strict in clinic. CONCLUSION: Cosmopost ceramic post has natural aesthetic
      effect and good strength. it can be used in clinic.

PMID- 14703490
TI  - [Effects of environmental estrogens on apoptosis induced by estrogen depletion in
      T47D cells].
AB  - OBJECTIVE: To explore the effects of environmental estrogens (n-4-noniphenol, NP;
      bisphenol, BisA; and dibutylphthalate, DBP) on apoptosis induced by estrogen
      depletion in breast cancer T47D cells. METHODS: Human T47D breast cancer cells
      were grown in DMEM medium containing 10% bovine serum. Four days before adding
      the test compounds, the cells were washed in phosphate-buffered saline, and the
      medium was substituted with a phenol red-free DMEM medium containing 5% dextral
      charcoal-stripped FBS. Respective test compound was added in fresh medium and the
      control cell received only the vehicle (ethanol). Apoptotic features in T47D cell
      were analyzed by light microscope that was commonly used to define apoptosis. DNA
      integrity of T47D cells was examined by agarose gel electrophoresis. Hypodiploid
      population was detected by flow cytometry. RESULTS: The typical characters of
      apoptosis in T47D cells were observed after estrogen deletion and then
      disappeared following exposure to T47D cells at 32 x 10(-7) mol/L Np and 32 x 10(
      7) mol/L BisA respectively. Inhibition of apoptosis at 32 x 10(-6) mol/L DBP was
      not shown in our study. CONCLUSION: N-4-noniphenol and Bisphenol A could inhibit
      apoptosis induced by estrogen deletion in breast cancer T47D cells. This result
      suggests that these environmental estrogens might involve in signal transduction
      connected with apoptosis.

PMID- 14703491
TI  - [Screening genes of differential expression in BALB/C mice thymus: a pilot study
      of effect of salmon milt DNA (SMD) on age-related involutions].
AB  - OBJECTIVE: To investigate the effect and its mechanism of salmon milt DNA (SMD)
      on age-related involutions in mouse thymus. METHODS: Female BALB/C mice aged 10
      months were divided randomly into three groups according to their weights. They
      were high dosage group (333.33 mg.kg(-1).b.w.d(-1)), low dosage group (166.67
      mg.kg(-1).b.w.d(-1)) and control group (0 mg.kg(-1).b.w.d(-1)). After five weeks,
      their thymus indexes were measured and the thymocytes were counted and the thymus
      cortex thicknesses were also measured using Image-Pro Plus (version. 4.0)
      software in the thymus section. All the data were analyzed by SAS statistic
      software. Microarray technique was applied to screen the gene fragments, which
      were differentially expressed between the high dosage group and the control
      group, together with RT-PCR to further confirm some of them. RESULTS: No
      significant differences of the variables including body weight, thymus weight and
      thymus indexes among the three groups were found. The thymocytes quantities of
      thymus cortex and medulla in the high dosage group were significantly higher than
      those of the control group (P < 0.01 and P < 0.05, respectively). The thymus
      cortex thicknesses of both SMD supplement groups were significantly higher than
      that of the control group (P < 0.01 and P < 0.05 respectively). 112 differently
      expressed gene fragments were isolated. Furthermore, we found the fragments with
      the logged number of U23789, X80232 and Aw209102 were highly expressed in the
      high dosage group when RT-PCR technique was used. CONCLUSIONS: SMD may reverse
      the age-related involutions in mouse thymus via up-regulation the expression of
      proliferation related genes and via up-regulation the expression of development
      and differentiation related genes simultaneously.

PMID- 14703492
TI  - [Construction of subtracted cDNA library in human Jurkat T cell line induced by
      arsenic trioxide in vitro].
AB  - OBJECTIVE: To understand the differentially expressed genes in human T
      lymphocytes induced by arsenic trioxide (As(2)O(3)) and to explore mechanism of
      its immunotoxicity and immune suppression. METHODS: Human Jurkat T cell line was
      treated by arsenic trioxide (5 micromol/L, 24 h) in vitro, as a sample model.
      Then, the differentially expressed genes were cloned and the subtractive cDNA
      library from Jurkat T cell line was constructed by suppression subtractive
      hybridization (SSH). Polymerase chain reaction (PCR) and sequencing techniques
      were applied to identify positive clones. RESULTS: The forward subtracted cDNA
      library contained differentially expressed genes from Jurkat T cell line induced
      by arsenic trioxide was constructed, including 29 different gene fragments and
      only replicated one in the subtracted cDNA library identified by PCR and
      sequencing analysis. These gene sequences were 95%-100% analogous to the genes in
      public database (GenBank/EMBL). The cDNA library contained oxidative metabolic
      genes in mitochondria (triose phosphate dehydrogenase, NADH4, pyrophosphate
      synthase, 16S rRNA ribosome, succinate-CoA ligase and ATP synthase 6);
      transcriptional and translation genes poly (A) binding protein, t-RNA-guanine
      transglycoslase, ribosomal protein L23, ribosomal protein S15A, eukaryotic
      translation initiation factor 3, Rab interaction protein 5, splicing factor
      arginine serine rich 5, and ADP-ribosylation factor-like 6 interacting protein),
      oxide stress related genes (ferritin high chain and high-mobility group protein
      2); protein activating and signaling pathway related genes (casein kinase, serine
      kinase 2 and phosphatidylinositol-four-phosphate adaptor protein-1-associated
      protein); cell differentiation and apoptosis associated genes (NB4 cell apoptosis
      related protein and myeloid differentiation primary response protein) and five
      genes with unknown function (KIAA0092, CGI-147protein, GCI-35, nucleolar
      phosphoprotein Nopp34 and Mus muscular partial mRNA for hypothetical protein), as
      well as a novel gene unmatched to the sequence in GenBank. CONCLUSIONS: The
      forward subtracted cDNA library contained differentially expressed genes from
      Jurkat T cell line induced by arsenic trioxide was successfully constructed. And,
      genes not involved in previous research on arsenic were found. Results of
      analysis for these genetic function suggested that there should be many genes
      involved in process of T lymphocytes apoptosis or injury induced by arsenic
      trioxide and that there should still be many genes associated with arsenic that
      were not reported in the past.

PMID- 14703493
TI  - [A case-control study on natural-resistance-associated macrophage protein 1 gene
      polymorphisms and susceptibility to pulmonary tuberculosis].
AB  - OBJECTIVE: To investigate association between the natural-resistance-associated
      macrophage protein 1 (NRAMP1) gene polymorphisms and susceptibility to pulmonary
      tuberculosis (TB) in Chinese Han population. METHODS: Hospital-based case-control
      study design was adopted. Polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP) technique were used to type three NRAMP1
      polymorphisms (INT4, D543N and 3'UTR). Information on related factors of
      tuberculosis was collected using a pre-tested standard questionnaire. Univariate
      and multivariate unconditional logistic analyses were conducted using SPSS for
      window software package. Totally, 110 cases of TB were selected during April 2001
      to June 2002, with an average age of (27.7 +/- 12.7) years. Also, 180 cases of
      healthy control were selected, aged (27.3 +/- 9.2) years in average. Locus of
      NRAMP1 polymorphism was analysed with univariate method. RESULTS: Univariate
      analysis demonstrated that the D543N G/A and 3'UTR TGTG+/del genotype occurred
      more frequently in the cases than in the controls, with crude odds ratios (OR)
      (95% CI) of 2.22 (1.03 - 4.78) and 1.93 (1.14 - 3.26), respectively. No
      significant association was observed between TB and INT4 polymorphisms. In
      multivariate analysis, associations of TB and D543N G/A and 3'UTR TGTG+/del
      genotypes remained, adjusted for exposure history and bacille Camette-Guerin
      immunization. Adjusted OR (95% CI) was 3.04 (1.12 - 8.27) and 2.36 (1.20 - 4.64),
      respectively. Still, no significant association between INT4 polymorphisms and TB
      was found. CONCLUSION: Polymorphisms of D543N and 3'UTR locus in NRAMP1 gene
      might affect their susceptibility to TB in Chinese Han population.

PMID- 14703494
TI  - [Influence of immunization dose schemes on the immune response to anti
      tetrodotoxin vaccine].
AB  - OBJECTIVE: To study the relationship between the immune response of anti
      tetrodotoxin vaccine, including its dose-response, and to select optimal
      immunization dose so as to enhance antitoxic effect of the anti-tetrodotoxin
      vaccine. METHODS: Tetrodotoxin (TTX) was coupled to Tachypleus tridentatus
      hemocyanin (TTH) chemically to form artificial antigen (TTX-TTH), and with which
      Balb/c mice were immunized. Influence of different immunization doses [100 microg
      as the higher (H) and 25 microg as the lower (L) dose group] on the protective
      effects of TTX vaccine was compared. The quality of antisera and effects of
      vaccine in anti-TTX poisoning were observed. RESULTS: The sera antibody quality
      increased more quickly in group L than that in group H after immunization. The
      dose at which the half of immunized mice survived when challenged once with TTX
      were 16 x LD (1 LD = 13.5 microg/kg, i.p.) in group L and 11 x LD in group H.
      When TTX was used time and again, the half of immunized mice could tolerate as
      high as 40 x LD and 22 x LD of accumulated dose, and the maximum tolerable
      cumulated dose was 104 x LD and 90 x LD for group L and H respectively. The
      scheme L was better both in antibody quality and effect of protecting against TTX
      toxicity than that in scheme H. CONCLUSIONS: The experimental vaccine of TTX
      could effectively protect animal from TTX intoxication. The lower immunization
      dose in this study is selected as the optimal immunization scheme.

PMID- 14703495
TI  - [Epidemiological features of registered cases of pulmonary tuberculosis in urban
      Guangzhou from 1994 to 2000].
AB  - OBJECTIVE: To understand epidemiological features of pulmonary tuberculosis in
      urban Giangzhou and tendency of its registered cases. METHODS: Registered data of
      pulmonary tuberculosis cases in urban Guangzhou during 1994 to 2000 were
      collected and analyzed comprehensively with method of descriptive epidemiology.
      RESULTS: Incidence of recently smear-positive registered rate (IRSPRR) increased
      from 16.68 per 100,000 in 1994 to 26.27 per 100,000 in 2000, with an average
      annual increase of 7.86%. The highest standardized IRSPRR was 33.70 per 100,000
      in Fangcun District. Average IRSPRR was 30.50 per 100,000 in males and 11.60 per
      100,000 in females. IRSPRR increased with age, with a peak of 61.22 per 100,000
      at age over 70, double as that at age of 50 - 69. Recently smear-positive
      registered case of pulmonary tuberculosis was highest in unemployment population,
      reaching 2529, accounting for 35.12% of the total. And, smear-positive registered
      rate decreased from 8.37 per 100,000 to 5.34 per 100,000, with an average annual
      reduction of 6.96%. Mortality of pulmonary tuberculosis decreased from 6.84 per
      100,000 to 4.41 per 100,000. CONCLUSIONS: It is necessary to keep in minds that
      highly prevalent area was extended from tuberculous epidemics. It is possible
      that unemployment people would be fallen into high-risk population. Potential
      source of infection should be found out as soon as possible.

PMID- 14703496
TI  - [Prevalence of vitamin A deficiency in children under six years of age in Tibet,
      China].
AB  - OBJECTIVE: To understand the prevalence of vitamin A deficiency (VAD) among
      children under six years of age in Tibet, China. METHODS: Totally, 1 257 children
      under six years of age were selected from two cities, two farming counties, two
      semi-farming counties and two livestock farming counties with stratified cluster
      sampling to asses VAD status in Tibet. Family information, children's feeding and
      disease history in the previous two weeks were collected by questionnaire. Blood
      specimen was collected from each child and serum was separated for detection of
      vitamin A concentration with microfluorescent spectrophotometry. RESULTS:
      Totally, 1 257 children under six years of age were surveyed, with 635 boys, 622
      girls, 862 aged over two years, and 98.5% of Tibet nationality. Six cases of
      night blindness and two cases of xerophthalmia were detected from them, with
      prevalence of clinical VAD of 0.96%. Eighteen of 1071 mothers with children under
      six years of age were found suffering from night blindness, accounting for 1.7%.
      Clinical cases of VAD both in children and mothers came from all four sampling
      strata. Average serum concentration of vitamin A and prevalence of subclinical
      VAD (serum vitamin A lower than or equal to 0.70 micromol/L) was 1.15 micromol/L
      and 5.4% and 1.12 micromol/L and 4.7% in cities and livestock farming counties,
      respectively, significantly higher than those in farming (1.04 micromol/L and
      11.0%) and semi-farming counties (1.05 micromol/L and 12.3%), respectively, as
      compared to average levels of 1.09 micromol/L and 8.4% in the autonomous region
      as a whole. Prevalence of subclinical VAD in children under six months and those
      aged six to eleven months were 22.2% and 13.3%, respectively, significantly
      higher than those in children aged one year (8.5%), two to three years (5.4%) and
      four to five years (7.9%), respectively. There was also significant difference in
      serum level of vitamin A between children at varied ages, but no significant
      difference both in serum level of vitamin A and prevalence of subclinical VAD
      between gender was found. CONCLUSIONS: In general, status of VAD in children of
      Tibet was milder than that at national level. But, moderate subclinical VAD in
      some areas, such as farming and semi-farming counties, did exist, so vitamin A
      supplementation aiming to children, especially those under one year of age, in
      those areas should be urged.

PMID- 14703497
TI  - [Effect of deoxynivalenol on action potentials of cultured cardiomyocytes and the
      protective effects of selenium].
AB  - OBJECTIVE: To study the effect of deoxynivalenol (DON), a mycotoxin produced by
      Fusarium graminearum, on action potentials of cultured cardiomyocytes and the
      possible protective effects of sodium selenite. METHODS: Ventricular myocytes
      from neonatal Wistar rats were cultured, and the transmembrane action potentials
      were recorded with glass microelectrodes before and after addition of DON at
      different concentrations. The cultured cardiomyocytes were pretreated with 0.5
      mg/L selenium (as sodium selenite) to observe the protective effects of selenium
      against the effects of DON. RESULTS: DON at concentrations of 50, 100 and 200
      mg/L decreased the action potential parameters including action potential
      amplitude (APA), overshoot (OS), threshold potential (TP), maximum rate of
      depolarization (Vmax) and action potential discharging frequency (APF), and
      prolonged the action potential duration of 10%, 50% and 90% repolarization
      (APD(10), APD(50) and APD(90)). Some of the parameters, such as APA, Vmax, APD
      and APF, changed in a concentration-dependent manner. The cultured cardiomyocytes
      pretreated with 0.5 mg/L of selenium for about 16 h presented only slight changes
      in action potential parameters induced by 200 mg/L DON. CONCLUSIONS: DON inhibit
      the membrane action potentials of cardiomyocytes, suggesting DON may interfere
      with the transmembrane movement of Ca(2+) and K(+), and sodium selenite may
      decrease the toxic effect of DON on cultured cardiomyocytes.

PMID- 14703498
TI  - [Study on the absorption, distribution and excretion of 3-chloro-1,2-propandiol
      in rats].
AB  - OBJECTIVE: To explore the absorption, distribution and excretion of 3-Chloro-1,2
      propandiol (3-MCPD) in healthy male SD rats after oral administration. METHODS: 3
      MCPD was administrated with a single oral dosage of 75 mg/kg BW to each rat.
      Samples of blood, tissues (including liver, kidney, brain and testicle) and
      excreta were then collected, and analyzed by the GC-MS method to determine 3-MCPD
      concentrations. The reported value is the mean value of three rats. RESULTS: At 2
      h after the administration, 3-MCPD concentrations in blood, testicle and kidney
      were (67.46 +/- 7.72), (78.37 +/- 5.15) and (56.21 +/- 3.64) microg/g,
      respectively. At 24 h, however, the corresponding values changed to (1.07 +/-
      0.97) microg/g, (49.43 +/- 28.18) microg/g and (11.41 +/- 2.55) microg/g. During
      the 24-hour period, 9.74 +/- 3.05% of the given parent compound was excreted in
      urine, whereas 0.56 +/- 0.22% and 0.28 +/- 0.03% were excreted in feces and bile,
      respectively, which implies that kidney is a major organ for excretion 3-MCPD.
      CONCLUSIONS: 3-MCPD was quickly absorbed through the alimentary tract and quickly
      distributed into a number of tissues, and then accumulated in the target organs,
      especially in the testicle. The excretion of the parent compound was largely
      through the kidney. It was inferred that 3-MCPD was mainly metabolized in the
      liver.

PMID- 14703499
TI  - [Study on the level of phthalates in human biological samples].
AB  - OBJECTIVE: To monitor the level of phthalates in human biological samples.
      METHODS: The concentrations of three commonly-used phthalate (di-ethyl phthalate,
      DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) in the human
      biological samples were measured by using reversed-phase HPLC. The blood serum
      samples were collected from 52 women and 8 men, semen specimens from 36 men, and
      fat samples from 6 women and 5 men. All these people were randomly selected, from
      23 to 50 years of age and residing in Shanghai. We also measured hormone levels
      of serum and conventional indices of semen specimens. RESULTS: The three
      phthalates were detected in most of the biological samples, with median levels of
      5.71 mg/L (ND-37.91 mg/L) in blood serum, 0.30 mg/L (0.08 -1.32 mg/L) in semen
      specimens, and 0.72 mg/kg (ND-2.19 mg/kg) in fat samples. The spearman
      correlation coefficients between concentrations of phthalates and levels of
      hormone in serum were 0.442 for DBP and E(2), and -0.486 for DEP and
      testosterone. There was a positive association between liquefied time of semen
      and semen concentrations of phthalates. The correlation coefficients were 0.456
      for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no
      significant difference between semen concentrations of phthalates and sperm
      density. CONCLUSION: These results suggest that people residing in Shanghai area
      are exposed to phthalates (particularly to DBP and DEHP) though the level is
      still relatively low.

PMID- 14703500
TI  - [An epidemiological study on sleep problems in children aged 1 to 23 months in
      Shanghai].
AB  - OBJECTIVE: To understand prevalence of sleep problems and presence of improper
      sleep habit of children aged one to 23 months in Shanghai, and to identify their
      related factors. METHODS: Totally, 1 252 normal children, without severe illness
      and abnormal delivery history, aged one to 23 months were randomly selected from
      five districts of Shanghai. Under strict quality control system, their parents
      were interviewed with questionnaire to look into their familial and social
      environment, as well as sleep-related factors. RESULTS: Fully-completed
      information was obtained in 1 129 of 1 252 children, with a response rate of
      90.18%. Prevalence of sleep problems in children was 65.90% in Shanghai,
      remarkably higher than in the other areas. Prevalence of nightmare, level of
      fright at night, snore and sleep apnea in boys were significantly higher than
      those in girls. Prevalence of improper sleep habit in children was also higher,
      including sleeping with their parents, parental presence at sleep onset and
      irregular sleep time. Main risk factors related to children's sleep problems were
      maternal anxiety, children's irregular sleep time, parental presence at sleep
      onset, difficulty-type temperament and maternal poor sleep during pregnancy.
      CONCLUSIONS: In Shanghai, prevalence of sleep problems in children aged one to 23
      months was relatively higher and main risk factors for them were social, cultural
      and familial environment, especially negligence of cultivating proper sleep habit
      and parental improper response to children's poor sleep behavior.

PMID- 14703501
TI  - [A survey on the dioxin level in breast milk in coastal and inland region].
AB  - OBJECTIVE: To study the dioxin level of breast milk among Chinese mothers, and to
      assess the dioxin intake of new-born babies from mother's milk and compare with
      the Tolerable Daily Intake (TDI) of dioxin. METHODS: The CALUX bioassay was used
      to detect the dioxin concentration of the first time mother's milk among the
      inland samples (Shenyang region; 32 cases) and the coastal city samples (Dalian
      region; 47 cases). RESULTS: The median value of the dioxin Toxic Equivalence
      (TEQ) in breast milk in the Dalian region was 15.84 pg TEQs.g(-1) fat, which was
      significantly higher than that in the Shenyang region 7.21 pg TEQs.g(-1) fat (P <
      0.01). CONCLUSION: The dioxin level in breast milk in Chinese is at the world's
      average level. The dioxin intake of the new-born babies during the period of
      lactation was higher than the lowest limit of the Tolerable Daily Intake (TDI)
      proposed by WHO. This situation should be noticed by the related authorities.

PMID- 14703502
TI  - [Expression and purification of varicella-zoster virus glycoprotein I gene in
      insect cells].
AB  - OBJECTIVE: To express the cloned gene glycoprotein I (gpI) of varicella-zoster
      virus (VZV), Beijing VZV 84-7 strain in insect cells and to purify its expression
      product. METHODS: The gene coding for gpI of VZV was amplified from viral DNA by
      PCR and cloned into baculovirus transfer vector (pBacPAK9), and recombinant
      transfer vector plasmid pBacVZVgpI was obtained. The inserted gpI gene in the
      pBacVZVgpI was sequenced. Insect cells Sf 9 were co-transfected with the
      recombinant transfer vector plasmid pBacVZVgpI and wild type linear baculovirus
      BacPAK6 (digested with Bsu36I) DNA. The recombinant baculoviruses containing the
      VZV 84-7 gpI gene was isolated through several rounds of limited dilution.
      Recombinant protein gpI was expressed in insect cells Sf 9, postinfected with
      recombinant baculoviruses. The expressed recombinant gpI was purified by lectin
      affinity chromatography and its antigenicity and immunogenicity were
      investigated. RESULTS: The gene coding for gpI of VZV was obtained by PCR and the
      gpI gene of pBacPAK9 was confirmed by DNA sequencing. The recombinant gpI was
      expressed in insect cells Sf 9, post-infected with recombinant baculovirus and
      identified by SDS-PAGE and western blotting, with its product in cell culture
      reaching the peak in 72 hours and with a molecular mass of 58 kd and 70 kd, the
      same as theoretical values. Results of immunoassay with cell lysates infected by
      recombinant baculoviruses indicated that recombinant protein expressed in insect
      cells had ability of eliciting specific antibodies against native VZV in mice and
      complement-dependent neutralizing antibodies. The purified recombinant gpI gave a
      product with a purity of more than 80%. ELISA and Western-blot analysis
      demonstrated that purified protein had specific VZV antibody-binding activity.
      This suggested that the recombinant gpI expressed in insect cells had the same
      biological characteristics as its native counterpart. CONCLUSION: Baculovirus
      insect cells could be used to express the gene of VZV gpI, which could provide a
      basis for quantitative analysis of VZV antigen, and preparation of its subunit
      vaccine.

PMID- 14703503
TI  - [Expression of uncoupling protein-2 mRNA in diet-induced obesity-resistant rats].
AB  - OBJECTIVE: To explore the expression of uncoupling protein-2 mRNA in brown
      adipose tissue, white adipose tissue and skeletal muscle of diet-induced obesity
      resistant (DIO-R) rats. METHODS: Fifty male Sprague-Dawley (SD) rats were
      randomly divided into a control group and a high-fat group and fed with basic
      diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were
      selected according to their body weight. The change of body weight and the intake
      of total calorie were observed. Reverse transcription-polymerase chain reaction
      (RT-PCR) was used to measure the expression of UCP2 mRNA in rat. RESULTS: Body
      weight and total calorie intake in DIO-R rats (425.1 +/- 27.1) g, (31,693 +/-
      946) kJ were significantly lower than those in DIO rats (489.7 +/- 20.5) g,
      (34,363 +/- 1465) kJ. The peak area of UCP2 mRNA in white adipose tissue in DIO-R
      rats was 352 +/- 30 and in DIO rats was 101 +/- 12. The peak areas of UCP2 mRNA
      in skeletal muscle in DIO-R and DIO rats were 130 +/- 15 and 170 +/- 12,
      respectively. The peak areas of UCP2 mRNA in brown adipose tissue of DIO and DIO
      R rats were 124 +/- 14 and 147 +/- 19, respectively. CONCLUSION: The expression
      of UCP2 mRNA in white adipose tissue of DIO-R rats increased significantly. These
      results suggest that obesity-resistance was associated with a tissue-specific
      increase in UCP2 expression.

PMID- 14703504
TI  - A novel cholesterol stain reveals early neuronal cholesterol accumulation in the
      Niemann-Pick type C1 mouse brain.
AB  - Niemann-Pick type C (NPC) is a neurodegenerative disorder characterized by
      progressive accumulation of cholesterol, gangliosides, and other lipids in the
      central nervous system and visceral organs. In the NPC1 mouse model,
      neurodegeneration and neuronal cell loss occur before postnatal day 21. Whether
      neuronal cholesterol accumulation occurs in vivo before the first signs of
      neuronal cell loss has not been demonstrated. In this report, we used the NPC1
      mouse model and employed a novel cholesterol binding reagent, BC theta, that
      enabled us to visualize cellular cholesterol accumulation at a level previously
      unattainable. The results demonstrate the superiority of BC theta staining over
      conventional filipin staining in confocal microscopy and highlight several new
      findings. We show that at postnatal day 9, although only mild signs of
      neurodegeneration are detectable, significant neuronal cholesterol accumulation
      has already occurred throughout the NPC1 brain. In addition, although NPC1
      Purkinje neurons exhibit a normal morphology at day 9, significant cholesterol
      accumulation within their extensive dendritic trees has occurred. We also show
      that in the thalamus and cortex of NPC1 mice, activated glial cells first appear
      at postnatal day 9 and heavily populate by day 22, suggesting that in NPC1 mice,
      neuronal cholesterol accumulation precedes neuronal injury and neuronal cell
      loss.

PMID- 14703505
TI  - ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein
      levels before and after treatment with atorvastatin.
AB  - The mechanisms responsible for interindividual variation in response to statin
      therapy remain uncertain. It has been shown that hepatic cholesterol synthesis is
      associated with ATP binding cassette transporter G5 and G8 (ABCG5/8) activities.
      To test the hypothesis that genetic variation in ABCG5/8 might influence the
      plasma lipid response to statin therapy, we examined five nonsynonymous
      polymorphisms at the ABCG5/8 loci (Q604E, D19H, Y54C, T400K, and A632V) in 338
      hypercholesterolemic patients treated with 10 mg atorvastatin. In carriers of the
      D19H variant, means of posttreatment values and adjusted percent reductions in
      LDL cholesterol (LDLC) were significantly lower (P = 0.028) and greater (P =
      0.036) (112 mg/dl, 39.7%) than those of noncarriers (119 mg/dl, 36.2%),
      respectively, while no significant difference was observed in percent reductions
      in total cholesterol. Stepwise multiple regression analysis revealed significant
      and independent associations with absolute or percent reduction between D19H
      genotype and posttreatment LDL cholesterol levels. The other polymorphisms were
      not significantly associated with treatment effects. These results suggest that,
      in patients with hypercholesterolemia, the ABCG8 D19H variant is associated with
      greater LDLC-lowering response to atorvastatin therapy.

PMID- 14703506
TI  - ASP enhances in situ lipoprotein lipase activity by increasing fatty acid
      trapping in adipocytes.
AB  - Acylation-stimulating protein (ASP) increases triglyceride (TG) storage (fatty
      acid trapping) in adipose tissue and plays an important role in postprandial TG
      clearance. We examined the capacity of ASP and insulin to stimulate the activity
      of lipoprotein lipase (LPL) and the trapping of LPL-derived nonesterified fatty
      acid (NEFA) in 3T3-L1 adipocytes. Although insulin increased total LPL activity
      (secreted and cell-associated; P < 0.001) in 3T3-L1 adipocytes, ASP moderately
      stimulated secreted LPL activity (P = 0.04; 5% of total LPL activity). Neither
      hormone increased LPL translocation from adipocytes to endothelial cells in a
      coculture system. However, ASP and insulin increased the V(max) of in situ LPL
      activity ([(3)H]TG synthetic lipoprotein hydrolysis and [(3)H]NEFA incorporation
      into adipocytes) by 60% and 41%, respectively (P </= 0.01) without affecting
      K(m). Tetrahydrolipstatin (LPL inhibitor) diminished baseline, ASP-, and insulin
      stimulated in situ LPL activity, resulting in [(3)H]TG accumulation (P < 0.0001).
      Unbound oleate inhibited in situ LPL activity (P < 0.0001) but did not eliminate
      the ASP stimulatory effect. Therefore, 1) the clearance of TG-rich lipoproteins
      is enhanced by ASP through increasing TG storage and relieving NEFA inhibition of
      LPL; and 2) the effectiveness of adipose tissue trapping of LPL-derived NEFAs
      determines overall LPL activity, which in turn determines the efficiency of
      postprandial TG clearance.

PMID- 14703507
TI  - Liver X receptors are regulators of adipocyte gene expression but not
      differentiation: identification of apoD as a direct target.
AB  - The liver X receptors alpha and beta (LXRalpha and LXRbeta) have been shown to
      play important roles in lipid homeostasis in liver and macrophages, however,
      their function in adipose tissue is not well defined. Both LXRs are highly
      expressed in fat, and the expression of LXRalpha increases during adipogenesis.
      Furthermore, LXRalpha expression is induced by peroxisome proliferator-activated
      receptor gamma (PPARgamma), the master regulator of fat cell differentiation.
      Here we investigate the role of LXRs in adipocyte differentiation and gene
      expression and their potential crosstalk with the PPARgamma pathway. We
      demonstrate that LXR agonists have no significant effect on the differentiation
      of 3T3-F442A or 3T3-L1 preadipocytes in vitro and do not alter the expression of
      differentiation-linked PPARgamma target genes in vivo. Moreover, retroviral
      expression of LXRalpha in NIH-3T3 cells does not alter the adipogenic potential
      of these cells and neither augments nor inhibits the action of PPARgamma.
      However, transcriptional profiling studies reveal that LXRs are important
      regulators of adipocyte gene expression. We identify the multifunction lipid
      carrier protein apolipoprotein D and the lipogenic protein Spot 14 as LXR
      responsive genes both in vitro and in vivo. Thus, although LXRs do not influence
      adipocyte differentiation per se, these receptors are likely to play an important
      role in the modulation of lipid metabolism in adipocytes.

PMID- 14703508
TI  - ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A
      I.
AB  - Prior studies provide data supporting the notion that ATP binding cassette
      transporter A1 (ABCA1) promotes lipid efflux to extracellular acceptors in a two
      step process: first, ABCA1 mediates phospholipid efflux to an apolipoprotein, and
      second, this apolipoprotein-phospholipid complex accepts free cholesterol in an
      ABCA1-independent manner. In the current study using RAW264.7 cells, ABCA1
      mediated free cholesterol and phospholipid efflux to apolipoprotein A-I (apoA-I)
      were tightly coupled to each other both temporally and after treatment with ABCA1
      inhibitors. The time course and temperature dependence of ABCA1-mediated lipid
      efflux to apoA-I support a role for endocytosis in this process. Cyclodextrin
      treatment of RAW264.7 cells partially inhibited 8Br-cAMP-induced efflux of free
      cholesterol and phospholipid to apoA-I. ABCA1-expressing cells are more sensitive
      to cell damage by high-dose cyclodextrin and vanadate, leading to increased
      lactate dehydrogenase leakage and phospholipid release even in the absence of the
      acceptor apoA-I. Finally, we could not reproduce a two-step effect on lipid
      efflux using conditioned medium from ABCA1-expressing cells pretreated with
      cyclodextrin.

PMID- 14703509
TI  - Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and
      impaired lipid metabolism in aged rats.
AB  - The effects of long-term carnitine supplementation on age-related changes in
      tissue carnitine levels and in lipid metabolism were investigated. The total
      carnitine levels in heart, skeletal muscle, cerebral cortex, and hippocampus were
      approximately 20% less in aged rats (22 months old) than in young rats (6 months
      old). On the contrary, plasma carnitine levels were not affected by aging.
      Supplementation of acetyl-l-carnitine (ALCAR; 100 mg/kg body weight/day for 3
      months) significantly increased tissue carnitine levels in aged rats but had
      little effect on tissue carnitine levels in young rats. Plasma lipoprotein
      analyses revealed that triacylglycerol levels in VLDL and cholesterol levels in
      LDL and in HDL were all significantly higher in aged rats than in young rats.
      ALCAR treatment decreased all lipoprotein fractions and consequently the levels
      of triacylglycerol and cholesterol. The reduction in plasma cholesterol contents
      in ALCAR-treated aged rats was attributable mainly to a decrease of cholesteryl
      esters rather than to a decrease of free cholesterol. Another remarkable effect
      of ALCAR was that it decreased the cholesterol content and cholesterol
      phospholipid ratio in the brain tissues of aged rats. These results indicate that
      chronic ALCAR supplementation reverses the age-associated changes in lipid
      metabolism.

PMID- 14703510
TI  - Separation and quantitative recovery of mouse serum arylesterase and
      carboxylesterase activity.
AB  - Paraoxonase-1 (PON1) is known to be associated with high density lipoproteins. We
      optimized buffer conditions to obtain quantitative recovery of PON1
      (arylesterase) activity and analyzed the distribution of PON1 in mice using a
      combination of size-exclusion chromatography and ultracentrifugation. Size
      exclusion chromatography of mouse serum separated the esterase activity into two
      peaks, one overlapping the high density lipoproteins and a second peak of lower
      molecular weight, consistent with serum carboxylesterase, which accounted for
      approximately 20% of the total esterase activity of normal mouse serum. Using
      conditions for the quantitative recovery of arylesterase activity, we
      fractionated serum by ultracentrifugation into d < 1.21 g/ml, d < 1.25 g/ml, d >
      1.21 g/ml, and d > 1.25 g/ml fractions. We observed that PON1 arylesterase
      activity and mass were isolated in the d < 1.21 g/ml fraction and that serum
      carboxylesterase was recovered in the d > 1.25 g/ml fraction. The significance of
      the confounding of PON1 arylesterase activity by serum carboxylesterase was
      demonstrated by studying mice challenged with a high-fat, high-cholate diet for
      14 days. It was shown that all of the decrease in arylesterase activity in
      response to this diet is attributable to the HDL-associated arylesterase activity
      (PON1). We conclude that mouse PON1 is quantitatively associated with high
      density lipoproteins. The contribution of serum carboxylesterase to the total
      esterase activity significantly confounds the interpretation of total
      arylesterase activity in mouse serum.

PMID- 14703511
TI  - Targeted disruption of the murine mucin gene 1 decreases susceptibility to
      cholesterol gallstone formation.
AB  - Gallbladder mucins play a critical role in the pathogenesis of cholesterol
      gallstones because of their ability to bind biliary lipids and accelerate
      cholesterol crystallization. Mucin secretion and accumulation in the gallbladder
      is determined by multiple mucin genes. To study whether mucin gene 1 (Muc1)
      influences susceptibility to cholesterol cholelithiasis, we investigated male
      Muc1-deficient (Muc1(-/-)) and wild-type mice fed a lithogenic diet containing 1%
      cholesterol and 0.5% cholic acid for 56 days. Gene expression of the gallbladder
      Muc1 and Muc5ac was significantly reduced in Muc1(-/-) mice in response to the
      lithogenic diet. Muc3 and Muc4 levels were upregulated and were similar between
      Muc1(-/-) and wild-type mice. Little or no Muc2 and Muc5b mRNAs were detected.
      Muc1(-/-) mice displayed significant decreases in total mucin secretion and
      accumulation in the gallbladder as well as retardation of crystallization,
      growth, and agglomeration of cholesterol monohydrate crystals. At 56 days of
      feeding, gallstone prevalence was decreased by 40% in Muc1(-/-) mice. However,
      cholesterol saturation indices of gallbladder bile, hepatic secretion of biliary
      lipids, and gallbladder size were comparable in Muc1(-/-) and wild-type mice. We
      conclude that decreased gallstone formation in mice with disrupted Muc1 gene
      results from reduced mucin secretion and accumulation in the gallbladder.

PMID- 14703512
TI  - Reciprocal regulation between Slt2 MAPK and isoforms of Msg5 dual-specificity
      protein phosphatase modulates the yeast cell integrity pathway.
AB  - Dual-specificity protein phosphatases (DSPs) are involved in the negative
      regulation of mitogen-activated protein kinases (MAPKs) by dephosphorylating both
      threonine- and tyrosine-conserved residues located at the activation loop. Here
      we show that Msg5 DSP activity is essential for maintaining a low level of
      signaling through the cell integrity pathway in Saccharomyces cerevisiae.
      Consistent with a role of this phosphatase on cell wall physiology, cells lacking
      Msg5 displayed an increased sensitivity to the cell wall-interfering compound
      Congo Red. We have observed that the N-terminal non-catalytic region of this
      phosphatase was responsible for binding to the kinase domain of Slt2, the MAPK
      that operates in this pathway. In vivo and in vitro experiments revealed that
      both proteins act on each other. Msg5 bound and dephosphorylated activated Slt2.
      Reciprocally, Slt2 phosphorylated Msg5 as a consequence of the activation of the
      cell integrity pathway. In addition, alternative use of translation initiation
      sites at MSG5 resulted in two protein forms that are functional on Slt2 and
      became equally phosphorylated following activation of this MAPK. Under activating
      conditions, a decrease in the affinity between Msg5 and Slt2 was observed,
      leading us to suggest that the mechanism by which Slt2 controls the action of
      Msg5 was via the modulation of protein-protein interactions. Our results indicate
      the existence of posttranscriptional mechanisms of regulation of DSPs in yeast
      and provide new insights into the negative control of the cell integrity pathway.

PMID- 14703513
TI  - Identification of Ser-386 of interferon regulatory factor 3 as critical target
      for inducible phosphorylation that determines activation.
AB  - Interferon regulatory factor (IRF)-3 is a critical transcription factor
      regulating innate immune responses against viral and bacterial infections.
      Signals activated by various pathogens are integrated by IRF-3 kinase, resulting
      in the specific phosphorylation of IRF-3 in the cytoplasm. This phosphorylation
      induces dimerization and association with the coactivators CREB-binding
      protein/p300, and the resultant complex activates the target genes in the
      nucleus. However, the phosphorylation sites that determine the active/inactive
      status of IRF-3 have been a source of controversy. In this study, we generated an
      antibody that specifically detects the phosphorylation of Ser-386 and used it as
      a probe. We found: 1) viral infection specifically induces phosphorylation of the
      Ser-386; 2) recently identified IRF-3 kinases (IKK-i/epsilon and TBK-1)
      phosphorylate Ser-386 and induce its dimerization; 3) phosphorylation of Ser-386
      is exclusively observed with the dimer; 4) mutation at Ser-386 abolishes the
      dimerization potential; 5) a constitutively active 5D mutant designed to mimic
      phosphorylation of Ser/Thr residues other than Ser-385 and -386 is secondarily
      phosphorylated at Ser-386, presumably by an irrelevant kinase. These results
      strongly suggest that Ser-386 is the target of the IRF-3 kinase and critical
      determinant for the activation of IRF-3.

PMID- 14703514
TI  - Interaction of an Arabidopsis RNA-binding protein with plant single-stranded
      telomeric DNA modulates telomerase activity.
AB  - Telomeres are the specialized structures at the end of linear chromosomes and
      terminate with a single-stranded 3' overhang of the G-rich strand. The primary
      role of telomeres is to protect chromosome ends from recombination and fusion and
      from being recognized as broken DNA ends. This protective function can be
      achieved through association with specific telomere-binding proteins. Although
      proteins that bind single-stranded G-rich overhang regulate telomere length and
      telomerase activity in mammals and lower eukaryotes, equivalent factors have yet
      to be identified in plants. Here we have identified proteins capable of
      interacting with the G-rich single-stranded telomeric repeat from the Arabidopsis
      extracts by affinity chromatography. Matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry analysis indicates that the isolated protein is
      a chloroplast RNA-binding protein (and a truncated derivative). The truncated
      derivative, which we refer to as STEP1 (single-stranded telomere-binding protein
      1), binds specifically the single-stranded G-rich plant telomeric DNA sequences
      but not double-stranded telomeric DNA. Unlike the chloroplast-localized full
      length RNA-binding protein, STEP1 localizes exclusively to the nucleus,
      suggesting that it plays a role in plant telomere biogenesis. We also
      demonstrated that the specific binding of STEP1 to single-stranded telomeric DNA
      inhibits telomerase-mediated telomere extension. The evidence presented here
      suggests that STEP1 is a telomere-end binding protein that may contribute to
      telomere length regulation by capping the ends of chromosomes and thereby
      repressing telomerase activity in plants.

PMID- 14703515
TI  - A p105-based inhibitor broadly represses NF-kappa B activities.
AB  - An IkappaBalpha-based NF-kappaB super repressor (sr) has been used widely for
      studying genes regulated by NF-kappaB transcription factors. Repression of NF
      kappaB by IkappaBalpha(sr) also facilitates tumor necrosis factor alpha-induced
      apoptosis in the cell. However, IkappaBalpha primarily targets RelA and c-Rel
      containing complexes, leaving other NF-kappaB/Rel protein complexes, such as p50
      and p52 homodimers, and RelB heterodimers uninhibited. Because these atypical NF
      kappaB complexes also contribute to gene regulation and are activated in
      pathological conditions, broad inhibition of all NF-kappaB species is of
      significant pharmacological and clinical interests. We have designed, generated,
      and tested a p105-based NF-kappaB super repressor. We showed that p105(sr), which
      no longer generates p50 and undergoes signal-induced degradation, effectively
      inhibits all NF-kappaB activities. In addition, we also demonstrated that
      p105(sr) significantly enhances tumor necrosis factor alpha-mediated killing of
      MT1/2 skin papilloma cells where p50 homodimer activity is elevated. Our results
      suggest that p105(sr) is a broader range and effective NF-kappaB super repressor
      and can potentially be used in cells where a noncanonical NF-kappaB activity is
      dominant or multiple NF-kappaB activities are activated.

PMID- 14703516
TI  - SC35 and heterogeneous nuclear ribonucleoprotein A/B proteins bind to a
      juxtaposed exonic splicing enhancer/exonic splicing silencer element to regulate
      HIV-1 tat exon 2 splicing.
AB  - Splicing of the human immunodeficiency virus, type 1, primary transcript is
      highly regulated. Maintaining the proper equilibrium among spliced, unspliced,
      and partially spliced isoforms is essential for the replication of the virus.
      Here we characterize a complex cis-acting element located in tat exon 2 that is
      required for the splicing regulation of the upstream intron. An exonic splicing
      enhancer (ESE) and an exonic splicing silencer (ESS) are both located within the
      regulatory element. Heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins
      bind the ESS to repress splicing, whereas the SR protein SC35 binds the ESE to
      activate it. We show that the SC35 and the hnRNP A1 binding sites overlap within
      the juxtaposed ESE/ESS. We propose that hnRNP A1 binding to the ESS inhibits
      splicing of the upstream intron by directly masking the SC35 binding site.

PMID- 14703517
TI  - Inter- and intra-octarepeat Cu(II) site geometries in the prion protein:
      implications in Cu(II) binding cooperativity and Cu(II)-mediated assemblies.
AB  - Cu(II) binding to the alpha prion protein (alphaPrP) can be both intramolecular
      and intermolecular. X-ray absorption spectroscopy at the copper K-edge has been
      used to explore the site geometry under each binding mode using both insoluble
      polymeric Cu(II).alphaBoPrP-(24-242) (bovine PrP) complexes and soluble Cu(II)
      complexes of peptides containing one, two, and four copies of the octarepeat.
      Analysis of the extended region of the spectra using a multiple scattering
      approach revealed two types of sites differing in the number of His residues in
      the first coordination shell of Cu(II). Peptides containing one and two
      octarepeat copies in sub-stoichiometric Cu(II) complexes showed the direct
      binding of a single His in accord with crystallographic intra-repeat geometry.
      Alternatively, the polymeric Cu(II).alphaBoPrP-(24-242) complex and Cu(II) in its
      soluble complex with a four-octarepeat peptide at half-site-occupancy showed
      Cu(II) directly bound to two His residues, consistent with an inter-repeat
      binding mode. Increasing the Cu(II) site occupancy from 0.5 to 0.75 in the
      peptide containing four octarepeats resulted in spectral features that are
      intermediate to those of the inter- and intra-repeat modes. The transition from
      His-Cu-His (inter-repeat) to Cu-His (intra-repeat) on increasing Cu(II)
      saturation offers a structural basis for the positive cooperativity of the cation
      binding process and explains the capacity of alphaPrP to participate in Cu(II)
      mediated intermolecular interactions.

PMID- 14703518
TI  - Molecular determinants responsible for differential cellular distribution of G
      protein-gated inwardly rectifying K+ channels.
AB  - Activation of the heteromeric G protein-gated inwardly rectifying K(+) channel
      (GIRK) GIRK1 and GIRK4 subunits gives rise to I(KACh), which controls
      excitability in atrial tissue. Although homomeric GIRK4 channels localize to the
      plasma membrane and display moderate function, GIRK1 channels fail to localize to
      the cell surface and do not exhibit significant function as homomers. Using
      oocytes to express GFP-tagged GIRK1 and GIRK4 and chimeras between these two
      proteins, we have identified two regions, one in the proximal C terminus and
      another in the distal N terminus that are critical for their subcellular
      localization. Replacement of both of these regions in GIRK1 with corresponding
      regions from GIRK4 was required for efficient expression of GIRK1 on the plasma
      membrane. Replacement of either region by itself was ineffective. The distal N
      terminus and proximal C terminus have been previously suggested to play important
      roles in ER-export and subunit co-assembly respectively in this family of
      channels. Our data indicate for the first time that both of these regions need to
      work in concert to mediate efficient targeting of these channels to the plasma
      membrane.

PMID- 14703519
TI  - Syntaxin 1A regulates ENaC channel activity.
AB  - Na(+) entry across the apical membranes of many absorptive epithelia is
      determined by the number (N) and open probability (P(o)) of epithelial sodium
      channels (ENaC). Previous results showed that the H3 domain of syntaxin-1A (S1A)
      binds to ENaC to reduce N, supporting a role for S1A in the regulation of ENaC
      trafficking. The aim of this study was to determine whether S1A-induced
      reductions in ENaC current also result from interactions between cell surface
      ENaC and S1A that alter ENaC P(o). Injection of a glutathione S-transferase (GST)
      H3 S1A fusion protein into ENaC-expressing Xenopus oocytes inhibited whole cell
      Na(+) current (I(Na)) by 33% within 5 min. This effect was dose-dependent, with a
      K(i) of 7 ng/microl (approximately 200 nm). In contrast, injection of GST alone
      or a H3 domain-deleted GST-S1A fusion protein had no effect on I(Na). In cell
      attached patch clamp experiments, GST-H3 acutely decreased ENaC P(o) by 30%,
      whereas GST-S1A Delta H3 was without effect. Further analysis revealed that ENaC
      mean closed time was significantly prolonged by S1A. Interestingly, GST-H3 had no
      effect on channel activity of an ENaC pore mutant that constitutively gates open
      (P(o) approximately equal 1.0), supporting the idea that S1A alters the closed
      state of ENaC and indicating that the actions of S1A on ENaC trafficking and
      gating can be separated experimentally. This study indicates that, in addition to
      a primary effect on ENaC trafficking, S1A interacts with cell surface ENaC to
      rapidly decrease channel gating. This rapid effect of S1A may modulate Na(+)
      entry rate during rapid increases in ENaC N.

PMID- 14703520
TI  - Structural studies on flavin reductase PheA2 reveal binding of NAD in an unusual
      folded conformation and support novel mechanism of action.
AB  - The catabolism of toxic phenols in the thermophilic organism Bacillus
      thermoglucosidasius A7 is initiated by a two-component enzyme system. The smaller
      flavin reductase PheA2 component catalyzes the NADH-dependent reduction of free
      FAD according to a ping-pong bisubstrate-biproduct mechanism. The reduced FAD is
      then used by the larger oxygenase component PheA1 to hydroxylate phenols to the
      corresponding catechols. We have determined the x-ray structure of PheA2
      containing a bound FAD cofactor (2.2 A), which is the first structure of a member
      of this flavin reductase family. We have also determined the x-ray structure of
      reduced holo-PheA2 in complex with oxidized NAD (2.1 A). PheA2 is a single domain
      homodimeric protein with each FAD-containing subunit being organized around a six
      stranded beta-sheet and a capping alpha-helix. The tightly bound FAD prosthetic
      group (K(d) = 10 nm) binds near the dimer interface, and the re face of the FAD
      isoalloxazine ring is fully exposed to solvent. The addition of NADH to
      crystalline PheA2 reduced the flavin cofactor, and the NAD product was bound in a
      wide solvent-accessible groove adopting an unusual folded conformation with ring
      stacking. This is the first observation of an enzyme that is very likely to react
      with a folded compact pyridine nucleotide. The PheA2 crystallographic models
      strongly suggest that reactive exogenous FAD substrate binds in the NADH cleft
      after release of NAD product. Nanoflow electrospray mass spectrometry data indeed
      showed that PheA2 is able to bind one FAD cofactor and one FAD substrate. In
      conclusion, the structural data provide evidence that PheA2 contains a dual
      binding cleft for NADH and FAD substrate, which alternate during catalysis.

PMID- 14703521
TI  - Open access publishing takes off.

PMID- 14703522
TI  - Treatment of major depressive disorder in children and adolescents.

PMID- 14703523
TI  - Choice and responsiveness for older people in the "patient centred" NHS.

PMID- 14703524
TI  - WHO's World Health Report 2003.

PMID- 14703526
TI  - Survey highlights health risks of overseas travel.

PMID- 14703528
TI  - Widespread flu in United States exposes shortage of vaccine.

PMID- 14703529
TI  - Italy to pass new law on assisted reproduction.

PMID- 14703530
TI  - Meadow faces GMC over evidence given in child death cases.

PMID- 14703531
TI  - Geneticist's sentence reduced in adoption ruling.

PMID- 14703532
TI  - Doctors hail new EU directive on tissues and cells.

PMID- 14703534
TI  - GMC clears head of Alder Hey of professional misconduct.

PMID- 14703535
TI  - WHO report says AIDS offers healthcare opportunity.

PMID- 14703536
TI  - Judge questions use of colposcopy photos in child abuse cases.

PMID- 14703538
TI  - Stable partnership and progression to AIDS or death in HIV infected patients
      receiving highly active antiretroviral therapy: Swiss HIV cohort study.
AB  - OBJECTIVES: To explore the association between a stable partnership and clinical
      outcome in HIV infected patients receiving highly active antiretroviral therapy
      (HAART). DESIGN: Prospective cohort study of adults with HIV (Swiss HIV cohort
      study). SETTING: Seven outpatient clinics throughout Switzerland. PARTICIPANTS:
      The 3736 patients in the cohort who started HAART before 2002 (median age 36
      years, 29% female, median follow up 3.6 years). MAIN OUTCOME MEASURES: Time to
      AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at
      least 50 and 100 above baseline, optimal viral suppression (a viral load below
      400 copies/ml), and viral rebound. RESULTS: During follow up 2985 (80%)
      participants reported a stable partnership on at least one occasion. When
      starting HAART, 52% (545/1042) of participants reported a stable partnership;
      after five years of follow up 46% (190/412) of participants reported a stable
      partnership. In an analysis stratified by previous antiretroviral therapy and
      clinical stage when starting HAART (US Centers for Disease Control and Prevention
      group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was
      0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable
      partnership compared with those without. Adjusted hazards ratios for other
      endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24)
      for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to
      1.14) for optimal viral suppression. CONCLUSIONS: A stable partnership is
      associated with a slower rate of progression to AIDS or death in HIV infected
      patients receiving HAART.

PMID- 14703539
TI  - Effect of low doses of ionising radiation in infancy on cognitive function in
      adulthood: Swedish population based cohort study.
AB  - OBJECTIVE: To determine whether exposure to low doses of ionising radiation in
      infancy affects cognitive function in adulthood. DESIGN: Population based cohort
      study. SETTING: Sweden. PARTICIPANTS: 3094 men who had received radiation for
      cutaneous haemangioma before age 18 months during 1930-59. MAIN OUTCOME MEASURES:
      Radiation dose to frontal and posterior parts of the brain, and association
      between dose and intellectual capacity at age 18 or 19 years based on cognitive
      tests (learning ability, logical reasoning, spatial recognition) and high school
      attendance. RESULTS: The proportion of boys who attended high school decreased
      with increasing doses of radiation to both the frontal and the posterior parts of
      the brain from about 32% among those not exposed to around 17% in those who
      received > 250 mGy. For the frontal dose, the multivariate odds ratio was 0.47
      (95% confidence interval 0.26 to 0.85, P for trend 0.0003) and for the posterior
      dose it was 0.59 (0.23 to 1.47, 0.0005). A negative dose-response relation was
      also evident for the three cognitive tests for learning ability and logical
      reasoning but not for the test of spatial recognition. CONCLUSIONS: Low doses of
      ionising radiation to the brain in infancy influence cognitive abilities in
      adulthood.

PMID- 14703540
TI  - Bad reporting does not mean bad methods for randomised trials: observational
      study of randomised controlled trials performed by the Radiation Therapy Oncology
      Group.
AB  - OBJECTIVE: To determine whether poor reporting of methods in randomised
      controlled trials reflects on poor methods. DESIGN: Observational study. SETTING:
      Reports of randomised controlled trials conducted by the Radiation Therapy
      Oncology Group since its establishment in 1968. PARTICIPANTS: The Radiation
      Therapy Oncology Group. Outcome measures Content of reports compared with the
      design features described in the protocols for all randomised controlled trials.
      RESULTS: The methodological quality of 56 randomised controlled trials was better
      than reported. Adequate allocation concealment was achieved in all trials but
      reported in only 42% of papers. An intention to treat analysis was done in 83% of
      trials but reported in only 69% of papers. The sample size calculation was
      performed in 76% of the studies, but reported in only 16% of papers. End points
      were clearly defined and alpha and beta errors were prespecified in 76% and 74%
      of the trials, respectively, but only reported in 10% of the papers. The one
      exception was the description of drop outs, where the frequency of reporting was
      similar to that contained in the original statistical files of the Radiation
      Therapy Oncology Group. CONCLUSIONS: The reporting of methodological aspects of
      randomised controlled trials does not necessarily reflect the conduct of the
      trial. Reviewing research protocols and contacting trialists for more information
      may improve quality assessment.

PMID- 14703541
TI  - The quality of randomised controlled trials may be better than assumed.

PMID- 14703542
TI  - Rash and acute nephritic syndrome due to candesartan.

PMID- 14703543
TI  - Randomised controlled trial of support from volunteer counsellors for mothers
      considering breast feeding.
AB  - OBJECTIVE: To investigate whether offering volunteer support from counsellors in
      breast feeding would result in more women breast feeding. DESIGN: Randomised
      controlled trial. SETTING: 32 general practices in London and south Essex.
      PARTICIPANTS: 720 women considering breast feeding. MAIN OUTCOME MEASURES:
      Primary outcome was prevalence of any breast feeding at six weeks. Secondary
      outcomes were the proportion of women giving any breast feeds, or bottle feeds at
      four months, duration of any breast feeding, time to introduction of bottle
      feeds, and satisfaction with breast feeding. RESULTS: Offering support in breast
      feeding did not significantly increase the prevalence of any breast feeding to
      six weeks (65% (218/336) in the intervention group and 63% (213/336) in the
      control group; relative risk 1.02, 95% confidence interval 0.84 to 1.24).
      Survival analysis up to four months confirmed that neither duration of breast
      feeding nor time to introduction of formula feeds differed significantly between
      control and intervention groups. Not all women in the intervention group
      contacted counsellors postnatally, but 73% (123/179) of those who did rated them
      as very helpful. More women in the intervention group than in the control group
      said that their most helpful advice came from counsellors rather than from other
      sources. CONCLUSIONS: Women valued the support of a counsellor in breast feeding,
      but the intervention did not significantly increase breastfeeding rates, perhaps
      because some women did not ask for help.

PMID- 14703544
TI  - Omega 3 fatty acids and cardiovascular disease--fishing for a natural treatment.

PMID- 14703545
TI  - Injury to the eye.

PMID- 14703546
TI  - Assessing the quality of research.

PMID- 14703547
TI  - Self poisoning with pesticides.

PMID- 14703548
TI  - Academic medicine: time for reinvention: medical education especially needs help.

PMID- 14703549
TI  - Academic medicine: time for reinvention: medical education, training, and
      research are under threat because academic medicine is undervalued.

PMID- 14703550
TI  - Academic medicine: time for reinvention: wholesale review of research and
      teaching is required.

PMID- 14703551
TI  - Academic medicine: time for reinvention: Hogwarts may be a useful analogy for
      improvement.

PMID- 14703552
TI  - Academic medicine: time for reinvention: academic medicine is failing women.

PMID- 14703553
TI  - Academic medicine: time for reinvention: academic research should wind down, not
      up.

PMID- 14703554
TI  - Academic medicine: time for reinvention: leadership and money are needed.

PMID- 14703555
TI  - Academic medicine: time for reinvention: public health sciences need
      strengthening in developing countries.

PMID- 14703556
TI  - Academic medicine: time for reinvention: encourage overseas based researchers to
      return to improve academic medicine in the developing world.

PMID- 14703557
TI  - Academic medicine: time for reinvention: what really matters?

PMID- 14703558
TI  - Academic medicine: time for reinvention: research needs researching.

PMID- 14703559
TI  - Academic medicine: time for reinvention: shorter training and shortage of doctors
      detrimentally affect research.

PMID- 14703560
TI  - Academic medicine: time for reinvention: teams are crucial for future clinical
      research.

PMID- 14703561
TI  - Academic medicine: time for reinvention: non-clinician scientists are the missing
      clinical links.

PMID- 14703562
TI  - Academic medicine: time for reinvention: MRC aims to give NHS evidence from
      randomised clinical trials.

PMID- 14703563
TI  - United Kingdom research governance strategy: reforming clinical research and
      development in England.

PMID- 14703565
TI  - Review of Hear the Silence: confusion has resulted from conflating two questions
      into one.

PMID- 14703566
TI  - Author's reply to letters on death in heat waves.

PMID- 14703567
TI  - Further nurses' notes on ER.

PMID- 14703568
TI  - Saddam Hussein's medical examination should not have been broadcast: images were
      designed to humiliate.

PMID- 14703569
TI  - Saddam Hussein's medical examination should not have been broadcast: doctors are
      not released from duty of care because of whom their patient is.

PMID- 14703570
TI  - Review of Hear the Silence: public needs to know why adverse reactions to
      vaccines occur.

PMID- 14703571
TI  - Saddam Hussein's medical examination should not have been broadcast: British
      television should not have followed suit.

PMID- 14703572
TI  - Cortical neurons arise in symmetric and asymmetric division zones and migrate
      through specific phases.
AB  - Precise patterns of cell division and migration are crucial to transform the
      neuroepithelium of the embryonic forebrain into the adult cerebral cortex. Using
      time-lapse imaging of clonal cells in rat cortex over several generations, we
      show here that neurons are generated in two proliferative zones by distinct
      patterns of division. Neurons arise directly from radial glial cells in the
      ventricular zone (VZ) and indirectly from intermediate progenitor cells in the
      subventricular zone (SVZ). Furthermore, newborn neurons do not migrate directly
      to the cortex; instead, most exhibit four distinct phases of migration, including
      a phase of retrograde movement toward the ventricle before migration to the
      cortical plate. These findings provide a comprehensive and new view of the
      dynamics of cortical neurogenesis and migration.

PMID- 14703573
TI  - Prefrontal cortical function and anxiety: controlling attention to threat-related
      stimuli.
AB  - Threat-related stimuli are strong competitors for attention, particularly in
      anxious individuals. We used functional magnetic resonance imaging (fMRI) with
      healthy human volunteers to study how the processing of threat-related
      distractors is controlled and whether this alters as anxiety levels increase. Our
      work builds upon prior analyses of the cognitive control functions of lateral
      prefrontal cortex (lateral PFC) and anterior cingulate cortex (ACC). We found
      that rostral ACC was strongly activated by infrequent threat-related distractors,
      consistent with a role for this area in responding to unexpected processing
      conflict caused by salient emotional stimuli. Participants with higher anxiety
      levels showed both less rostral ACC activity overall and reduced recruitment of
      lateral PFC as expectancy of threat-related distractors was established. This
      supports the proposal that anxiety is associated with reduced top-down control
      over threat-related distractors. Our results suggest distinct roles for rostral
      ACC and lateral PFC in governing the processing of task-irrelevant, threat
      related stimuli, and indicate reduced recruitment of this circuitry in anxiety.

PMID- 14703574
TI  - Biochemical and genetic interaction between the fragile X mental retardation
      protein and the microRNA pathway.
AB  - Fragile X syndrome is caused by a loss of expression of the fragile X mental
      retardation protein (FMRP). FMRP is a selective RNA-binding protein which forms a
      messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes.
      Recently, mRNA ligands associated with FMRP have been identified. However, the
      mechanism by which FMRP regulates the translation of its mRNA ligands remains
      unclear. MicroRNAs are small noncoding RNAs involved in translational control.
      Here we show that in vivo mammalian FMRP interacts with microRNAs and the
      components of the microRNA pathways including Dicer and the mammalian ortholog of
      Argonaute 1 (AGO1). Using two different Drosophila melanogaster models, we show
      that AGO1 is critical for FMRP function in neural development and synaptogenesis.
      Our results suggest that FMRP may regulate neuronal translation via microRNAs and
      links microRNAs with human disease.

PMID- 14703575
TI  - [Health economic consequences of the use of irbesartan in patients in Germany
      with type 2 diabetes, nephropathy and hypertension].
AB  - BACKGROUND AND AIMS: The "Irbesartan in Diabetic Nephropathy Trial" (IDNT),
      demonstrated a reduction in the combined endpoint of doubling of serum
      creatinine, end-stage renal disease (ESRD) or death compared to control or
      amlodipine arms in patients with hypertension, type 2 diabetes and overt
      nephropathy when treated with irbesartan. Aim of this study is to compare long
      term consequences in costs and outcomes of IDNT treatment alternatives from the
      German health care system's perspective. METHODS: A Markov model simulated
      progression from overt nephropathy to doubling of serum creatinine, end-stage
      renal disease, and death in patients with hypertension, type 2 diabetes and overt
      nephropathy for the three treatment arms. Treatment-specific probabilities were
      derived from IDNT. German-specific ESRD-related data were retrieved from
      published sources to reflect local management practices, ESRD outcomes and costs.
      A time horizon of 10 years was used. Delay in onset of ESRD and mean costs per
      patient were calculated. Future costs were discounted at 5 % per annum. RESULTS:
      The cumulative incidence of ESRD after 10 years with irbesartan (36 %) is lower
      compared to amlodipine (49 %) or control (45 %). Irbesartan leads to cost savings
      of 14 424 EUR and 8 720 EUR per patient versus amlodipine or control
      respectively. CONCLUSION: Treating patients with hypertension, type 2 diabetes
      and nephropathy using irbesartan lowers the cumulative incidence of ESRD and is
      cost-saving compared to amlodipine or control.

PMID- 14703577
TI  - [Hereditary intestinal cancer. Linking a specialized center with general medical
      practice].

PMID- 14703576
TI  - [Alternating electric heart axis in a patient with small cell lung cancer].
AB  - HISTORY AND ADMISSION FINDINGS: A 62-year-old man was admitted because of
      recurrent abdominal pain 18 months after small cell lung cancer (SCLC) had been
      diagnosed and remission achieved with chemotherapy and radiotherapy. The abdomen
      was soft on palpation, but pressure on the epigastric region was painful.
      Symptomatic treatment brought improvement, but 16 hours after admission the
      patient complained of severe diffuse abdominal pain. Abdominal findings were
      unchanged. He was pale and in a cold sweat. Heart sounds were decreased, while
      auscultation and percussion of the lung were unremarkable. INVESTIGATION: Lactate
      dehydrogenase and aspartate-aminotransferase concentrations were markedly raised
      and the serum creatinine was increased, while the Quick value was decreased. The
      electrocardiogram (ECG) showed low voltage and alternating electrical heart axis.
      Chest radiogram demonstrated a double-contour cardiac silhouette suggesting a
      large pericardial effusion, confirmed on echocardiography, which also showed a
      pendulum-like cardiac motion. The needle aspirate of the pericardial fluid
      contained malignant cells. DIAGNOSIS: These findings indicated malignant,
      hemodynamically significant pericardial effusion due to a recurrence of SCLC,
      with pronounced abdominal symptoms and advanced right heart failure. TREATMENT
      AND COURSE: Pericardiocentesis brought about marked improvement. 30 mg cisplatin
      was injected into the pericardial sac and chemotherapy resumed. The ECG became
      normal. There was no tumor progression over the following 4 months when the
      pericardial effusion recurred, chemotherapy (4 cycles of carboplatin and
      etoposide) was restarted and another infusion of cisplatin undertaken.
      CONCLUSION: This case report illustrates a not uncommon manifestation of lung
      cancer, malignant pericardial effusion, first becoming symptomatic as severe
      abdominal pain. Characteristic changes in the chest radiogram and the ECG
      provided the diagnosis, confirmed histologically.

PMID- 14703578
TI  - [Patent foramen ovale: an underrated risk for divers?].
AB  - The foramen ovale which is the fetal connection between the right and left atrium
      persists in about 30 % of the adult population. In the presence of a persistent
      foramen ovale (PFO) shunting of blood may occur from the right to the left
      atrium, and bubbles can reach the systemic circulation during or after the
      decompression phase of a dive with compressed air. Therefore, divers with PFO may
      have an increased risk to develop ischemic cerebral lesions and neurologic
      decompression sickness (DCS). Significant right-to-left shunting may be diagnosed
      using transcranial doppler ultrasound of the medial cerebral artery and
      echocardiography with echo contrast media and Valsalva provocation. However,
      there are no official guidelines concerning PFO screening in medical fitness
      exams for professional or recreational divers in Germany. Therefore, it remains
      in the diver's choice to be screened for PFO. Divers with a history of DCS should
      be monitored for PFO, especially when diving strictly adhered to decompression
      tables. Divers with PFO who refuse to stop diving after DCS should be advised to
      adhere to very save dive profiles.

PMID- 14703579
TI  - [Heat shock proteins, immune competence and vaccination].

PMID- 14703580
TI  - [Can we afford the costs of progress in intensive care medicine? A plea for a
      candid debate].
AB  - Intensive care medicine is one of the most fast growing segments in medicine. New
      substances that may improve therapy of the critically ill dramatically have
      entered the market. Improvements include therapy of methicilline-resistant
      Staphylococcus aureus (MRSA) infections (linezolid), severe heart failure
      (calcium sensitizer levosimendan), intractable bleeding (recombinant factor VIIa)
      and severe sepsis (recombinant activated protein C (aPC)). The anticipations
      concerning this new strategies of intensive care therapy are high, but use of the
      new substances is associated with extreme costs. In the past, pharmaceutical
      therapy represented only a small aspect of all costs in the intensive care unit
      (ICU). Using this new substances, we are entering a new dimension of costs. One
      case of recombinant factor VIIa or recombinant aPC increases costs by
      approximately 10000,- Euro. At the moment, this costs are not covered by extra
      budgets. It is still unclear whether by using this new therapeutic strategies
      other costs can be reduced and the extreme extra-costs can be balanced. The
      elderly population will increase dramatically in the next years. Looking at this
      development, it is not only the question whether we can afford intensive care
      medicine, but the question has to be enlarged whether we can afford the new
      developments of intensive care medicine. All responsible persons (intensivists,
      pharmaceutical companies, politicians) are urged to define solutions in the near
      future.

PMID- 14703581
TI  - [Treatment of H. pylori infection--always necessary--pro].

PMID- 14703582
TI  - [Helicobacter pylori eradication: always?--contra].

PMID- 14703585
TI  - A Festschrift in Honor of Dr. Peter Auld.

PMID- 14703586
TI  - The young man from Canada.

PMID- 14703587
TI  - The fetus as a patient: an essential concept for the ethics of perinatal
      medicine.
AB  - This article celebrates the professional life and contributions of Dr. Peter
      Auld, a founder of perinatal medicine. To this end we describe the essential
      concept of the fetus as a patient, based on two core ethical principles,
      beneficence and respect for autonomy. We explore the implications of this concept
      for perinatal medicine.

PMID- 14703588
TI  - Antibiotics and other anti-infective agents in pregnancy and lactation.
AB  - Serum levels of many drugs are lower in pregnancy compared with the nonpregnant
      state. Their renal clearance is higher and the maternal intravascular volume is
      expanded. Most antibiotics are safe for use in pregnancy and lactation.
      Tetracyclines cause fetal tooth discoloration and inhibition of bone growth if
      used in the second and third trimesters. Aminoglycosides carry a small risk of
      fetal ototoxicity. Quinolones may cause arthropathies in children, and so are
      currently not recommended for use in pregnancy. Most drugs are secreted into
      breast milk in very small amounts, not enough to have any therapeutic effect. The
      only antibiotics which may be of concern in nursing infants are sulfonamides and
      quinolones, and possibly metronidazole.

PMID- 14703589
TI  - Hyperbilirubinemia in the 2000s: what should we do next?
AB  - Changes in healthcare policy mandating early discharge of healthy, full-term
      infants and the higher prevalence of breast-feeding of newborns have contributed
      to an increased number of term infants being readmitted to the hospital for
      hyperbilirubinemia. At high levels, total serum bilirubin causes kernicterus,
      which is associated with severe neurological sequelae. This article provides a
      review of prior studies that have examined whether and at what levels total serum
      bilirubin affects neurodevelopmental outcome in term infants. In addition, the
      article reviews some approaches in the literature that suggest means of
      preventing high levels of hyperbilirubinemia in term infants.

PMID- 14703590
TI  - Fetal and neonatal cytopenias: what have we learned?
AB  - Rh disease has largely disappeared as a result of prophylaxis with anti-D.
      However, the cases that remain are more complicated with a combination of novel
      challenges with regard to in utero management with transfusion and its effects on
      the course of the neonate, both early and late. Thrombocytopenia in the neonate
      can be severe and recurrent if it is a result of alloimmunization. Newer
      techniques in the laboratory have improved the security of diagnosis. Antenatal
      management of affected fetuses with treatment administered to the mother is now
      well established although studies are ongoing. Neutropenia is a complication of
      pre-eclampsia; the mechanism is still not well understood.

PMID- 14703591
TI  - Neonatology and emerging trends in health insurance.
AB  - As the cost of healthcare rises, the employers who finance health insurance
      benefits plans are demanding increased accountability and effectiveness in the
      management of costly care, such as that delivered in the neonatal intensive care
      unit. Neonatologists are under increased scrutiny by third-party payors. They
      should also expect to see closer case management, downgraded reimbursement
      according to standardized tools for assessing level of care, and closer
      evaluation of reimbursement for novel and expensive drugs and technologies.
      Neonatologists need to become more knowledgeable about how the current crisis in
      cost for employer-funded health plans may affect their practice.

PMID- 14703592
TI  - Trends in the NICU: a review of 25 years' experience.
AB  - A review of 25,448 admissions was performed to evaluate the progress of neonatal
      intensive care at Weill Cornell Medical Center since 1978. Patients were
      identified by a review of admission and discharge data compiled by admitting
      staff. The following data were collected: birth weight, gestational age, place of
      birth (inborn versus outborn), discharge date, disposition. Length of stay was
      computed from these data. Data were organized according to year of admission.
      Admissions remained relatively constant with time. However the percentage of
      inborn infants steadily increased. Survival of the smallest infants (<600 g)
      remained poor, but overall survival of all infants improved over time. Length of
      stay for infants 1000 to 2000 g fell over time while that of other infants
      remained constant. These trends reflect changes in obstetric and neonatal
      practice over time, and include improved methods of antenatal care, neonatal
      pulmonary care, and nutrition, as well as changes in the distribution of neonatal
      and high-risk maternal care.

PMID- 14703593
TI  - End-tidal CO2 as a function of tidal volume in mechanically ventilated infants.
AB  - OBJECTIVE: To test the hypothesis that end-tidal CO(2) (PETCO(2)) varies with
      tidal volume (Vt) in preterm infants. DESIGN: Intervention study, nonrandomized
      trial. SETTING: Neonatal ICU, regional referral center. SUBJECTS: 29 preterm
      infants 790 to 2135 g in weight requiring mechanical ventilation studied on 73
      occasions. INTERVENTION: Measurement of PETCO(2) during variations of Vt.
      MEASUREMENT: Statistical correlation of PETCO(2) to Vt. RESULT: PETCO(2) is
      minimal when Vt is either too low or too high. CONCLUSION: Vt, through its effect
      on dead space/Vt (Vd/Vt) ratios and arterial-alveolar CO(2) differences, has a
      significant effect on PETCO(2). Observation of PETCO(2) across a range of Vt can
      be used to select an appropriate Vt for preterm infants requiring mechanical
      ventilation.

PMID- 14703594
TI  - Low-birth-weight neonates exhibit a physiological set-point to regulate CO2: an
      untapped potential to minimize volutrauma-associated lung injury.
AB  - The objective of this article is to determine whether low-birth-weight (LBW)
      infants have the capacity to modulate minute ventilation to achieve a CO (2) set
      point within ranges acceptable to clinicians during a procedure designed to
      identify the best dynamic compliance loops. By using dynamic flow-loop mechanics,
      we performed a prospective stepwise reduction of tidal volume (by reduction of
      peak inspiratory pressure, keeping end-expiratory pressure constant), in a group
      of LBW infants to identify the steepest slope of the dynamic flow-loop. We used
      flow-synchronized, assist-control mechanical ventilation with termination
      sensitivity set at 5%. Vital signs and blood gases were assessed every 15 minutes
      at each stepped-pressure change during the first hour after enrollment and after
      12 hours, to evaluate oxygenation and ventilation. Peak inspiratory pressure
      (PIP) was selected at the lowest level that achieved target range blood gases.
      The acute reduction of PIP and the resulting lower tidal volume was initially
      associated with an increase in the spontaneous respiratory rate in the first hour
      that also was associated with a significant decrease in patient-selected
      inspiration time. After 12 hours, the spontaneous respiratory rate returned to
      baseline; the peak PaCO(2) was 43.8 +/- 2.03 (mean +/- SEM). LBW infants have the
      capacity to alter respiratory rate to change minute ventilation in response to a
      reduction of tidal volume created by lowering the PIP. Using this model of
      endogenous CO(2) challenge in ventilated infants, we conclude that LBW neonates
      have the capacity to select a CO(2) set-point. This approach suggests an
      important avenue through which a clinician can minimize volutrauma through a
      reduction of PIP and use of expiratory trigger to limit excessive PIP and an
      overall lower mean airway pressure.

PMID- 14703595
TI  - Lymphocyte subpopulations in bronchopulmonary dysplasia.
AB  - A key role for inflammation in the etiology of bronchopulmonary dysplasia (BPD)
      has been proposed. In the present study we have evaluated lymphocyte
      subpopulations in 39 premature infants with respiratory distress syndrome (RDS)
      who did or did not develop BPD. The absolute number of lymphocytes was lower
      among infants with RDS who developed BPD compared with those who did not over the
      first two weeks of life ( p < 0.020) as were percentage and absolute number of
      CD4(+) T cells. By contrast, the proportions of CD3(+)CD8(+) lymphocyte cells
      were not statistically different between non-BPD and BPD infants. B cell
      percentage was significantly decreased in BPD infants only on day 7. NK "bright"
      cells (CD56(+)) were highly enriched in all RDS groups. Interestingly, the
      percentage of CD4(+) T cells expressing CD62L was selectively reduced in BPD
      infants. As a whole these data suggest that reduction of CD4(+) T cells and
      especially those important in tissue migration and immune surveillance may be a
      factor in the pathogenesis of BPD.

PMID- 14703596
TI  - Factors influencing initiation of breast-feeding among urban women.
AB  - The objective of our study was to identify factors associated with the initiation
      of breast-feeding in a poor urban area. One hundred postpartum, nonadolescent,
      non-drug using mothers, 50 breast-feeding and 50 formula feeding, were
      consecutively interviewed. Breast-feeding women were more likely to be born
      outside of the United States (42 versus 14%, p = 0.002), have more years of
      education (12.1 +/- 1.9 versus 10.9 +/- 1.7, p = 0.002), be employed either prior
      to or during pregnancy (38 versus 16%, p = 0.000), be married (46 versus 26%, p =
      0.037), be a nonsmoker (86 versus 64%, p = 0.011), have more prenatal visits (8.4
      +/- 7.3 versus 5.0 +/- 5.9, p = 0.010), or have a breast-feeding mother (48
      versus 26%, p = 0.023). There were no differences in age or ethnicity. The father
      of the breast-feeding baby was more likely to be better educated (12.0 +/- 2.8
      versus 10.5 +/- 3.6 years, p = 0.022) and to work full-time (68 versus 40%, p =
      0.005). Eighty-four percent of formula feeders knew that breast milk was better
      for their babies but decided not to breast-feed due to concerns of pain, smoking,
      and work. Sixty-three percent of women made the choice to breast-feed prior to
      the pregnancy, 26% during the pregnancy, and 11% after delivery. Significantly
      more multiparas decided prior to the pregnancy compared with primaparas. We
      recommend that breast-feeding education should be started prior to the first
      pregnancy and tailored to the concerns of the women.

PMID- 14703597
TI  - Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg.
AB  - We studied babies (22 to 32 weeks gestational age) of mothers wishing to breast
      feed. Group 1 received 1 mg of vitamin K and Group 2 received 0.5 mg of vitamin
      K. The Day 2 plasma levels of vitamin K were 1900 to 2600 times higher on
      average, and the Day 10 vitamin K levels 550 to 600 times higher on average,
      relative to normal adult plasma values, whether an initial prophylaxis dose of
      0.5 mg or 1 mg was used. We conclude that 0.5 mg as the initial dose of vitamin K
      intramuscularly or intravenously would likely be more than adequate to prevent
      hemorrhagic disease of the newborn, and that 0.3 mg/per kg may be used for babies
      with birth weights below 1000 g. To decrease vitamin K intakes in this
      population, new preparations of total parenteral nutrition multivitamins are
      needed.

PMID- 14703599
TI  - "Primum Non Nocere".

PMID- 14703598
TI  - Diagnostic value of cytokines and C-reactive protein in the first 24 hours of
      neonatal sepsis.
AB  - The first objective of this article was to determine the diagnostic accuracy of
      tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in
      differentiating infected from noninfected neonates during the first 24 hours of
      suspected sepsis and to compare them to the currently used laboratory parameters:
      C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and
      platelet count. The secondary objective was to compare the cytokine levels in
      subpopulations of neonates. Seventy-five premature and 30 term infants were
      enrolled. Blood samples for the "currently used laboratory tests" and the
      cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18
      to 30 hours later ("24-hours"). Patients were classified as septic (48) or
      nonseptic (57). Thirty-two septic patients had positive blood cultures and 16
      showed clinical signs of sepsis. Twenty septic patients had early-onset and 28
      had late-onset sepsis. Sensitivity, specificity, and positive and negative
      predictive values (PPV and NPV) were calculated for each test. Receiver-operating
      characteristic curves were analyzed to determine the optimal thresholds. A
      combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%,
      specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP
      (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6
      at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the
      patients infected with coagulase-negative staphylococci then with other bacteria.
      In conclusion, a combination of CRP + IL-6 provided additional diagnostic
      accuracy for differentiation between septic and nonseptic patients during the
      first 24 hours of suspected sepsis.

PMID- 14703600
TI  - Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) describes xeropthalmia and xerostomia due to lymphocytic
      infiltrates of lacrimal and salivary glands. SS may occur alone (primary SS) or
      in association with several other autoimmune diseases (secondary SS). The
      clinical features involve a wide variety of organs, including skin, eyes, oral
      cavity and salivary glands, and systems, including nervous, musculoskeletal,
      genitourinary and vascular. Sicca symptoms can be found in a number of other
      disorders including rheumatoid arthritis, systemic lupus erythematosus,
      scleroderma, primary biliary cirrhosis, and other rheumatic disorders.

PMID- 14703601
TI  - Preventive effects of intracisternal alphatochopherol on cerebral vasospasm in
      experimental subarachnoid haemorrhage.
AB  - Vasospasm is an important cause of morbidity and/or mortality with a subarachnoid
      haemorrhage (SAH). The roles of lipid peroxidation in a vasospasm caused by a SAH
      remain to be investigated. The effect of an intracisternal administration of
      alphatochopherol on a cerebral vasospasm was investigated in an experimental
      model. The authors assessed whether the administration of alphatochopherol
      reduced the vasospasm. By means of an intracisternal blood injection model, a SAH
      was induced in 30 rats, which were randomly divided into three groups, as
      follows: group I (G1), without a SAH and drug, group II (G2), a SAH alone, group
      III (G3), a SAH and alphatochopherol. Following the withdrawal of cerebrospinal
      fluid (CSF), a fresh unheparinized arterial blood was injected into the cisterna
      magna to induce a SAH. In G3, 20 U (0.4ml) alphatochopherol was intracisternally
      injected forty-five hours after induction of the SAH. All rats were sacrificed 72
      hours after the induction. The basilar artery, with surrounding tissue, was
      removed from the cranium. The cross-sectional diameter of the lumen and vessel
      wall of the rat basilar artery was assessed from a planimetric analysis, and
      changes compared with G1 and G2. The reduction in the luminal cross-sectional
      diameter of the vessels exposed to subarachnoid blood was found to be 29.01 %
      (p=0.001). The group treated with alphatochopherol had a 9% reduction (p=0.004).
      The role of lipid peroxidation on a vasospasm caused by SAH is well known to be
      critical. Data from the present study indicated that antioxidant therapy, with
      topical alphatochopherol, may be promising on a vasospasm caused by a SAH.

PMID- 14703602
TI  - Gastrointestinal side effect profile due to the use of alendronate in the
      treatment of osteoporosis.
AB  - The aim of our study was to evaluate the upper gastrointestinal (GI) tract side
      effect profile in 759 female patients that had taken alendronate (10 mg/day), for
      at least 6 months, for the treatment of osteoporosis, in relation to the safety
      of alendronate and the compliance of patients to its absorption rules. This study
      was a multicentered retrospective, clinical, non- placebo controlled, study of
      759 female subjects carried out at 26 centres in 6 different regions of Turkey.
      The mean age of our patients was 62.6 +/- 8.6, with 51.2%in the age range 60 to
      69 years. 158 patients (20.8%) were considered to have upper GI tract complaints
      with nausea as the most often encountered symptom. Of the subjects with upper GI
      tract complaints, 20% reported discontinued drug use, and 30% reported the
      requirement of an additional drug in order to abolish their complaints.
      Approximately 537 (71%) of the patients stated they had been given written
      information about the administration of the drug, and at least 93 patients (12%)
      and 73 patients (18.4%) acknowledged non compliance with the safety and
      absorption rules, respectively. In our study, no significant difference was found
      between the adherence to the safety measures and upper GI tract complaints (p >
      0.05), but that upper GI tract complaints were higher in patients taking
      additional medication to alendronate (p < 0.05).

PMID- 14703603
TI  - Characterization of the pulmonary circulation according to hemodynamic changes by
      computed tomography.
AB  - Increased or decreased pulmonary blood flow (PBF) and an increased pulmonary
      vascular resistance (PVR), represent common and important change in pulmonary
      hemodynamics. In this study, we constructed 3 hemodynamic models in 5 dogs, that
      is, an increased and a decreased PBF model, and an increased PVR model. A CT
      perfusion scan was performed in each hemodynamic model. Perfusion parameters
      including blood flow (BF), blood volume (BV), mean transit time (MTT), and
      maximal slope (MS) were calculated automatically by specialized software and
      analyzed for changes according to hemodynamic status. In terms of the normal
      state, blood flow was affected by gravity and dependent area showed higher BF and
      BV and lower MS and MTT than the non-dependent area. The decreased PBF model
      showed a significant increase in BF and MS (p=0.046, 0.005) but no significant
      change in BV (p > 0.05), and a slight elongation of MTT (p > 0.05) versus the
      normal state. The increased PBF model showed a slightly increased BV and a
      slightly decreased MTT (p > 0.05). The increased PVR model showed significant
      reduction in BF, BV, and MS (p < 0.000, 0.007, 0.000) and a slight increase in
      MTT, but without statistical significance (p > 0.05). However, it was noticeable
      that the distribution of MTT with respect to gravity in the normal lung was
      completely reversed in the increased PVR model. In conclusion, based on our
      understanding of perfusion characteristic in normal state, abnormal regional
      hemodynamic changes in the lung can be detected and evaluated. Predicting changes
      in pulmonary vascular resistance should be possible by a thorough analysis of CT
      perfusion parameters.

PMID- 14703604
TI  - Lipid peroxidation, erythrocyte superoxide-dismutase activity and trace metals in
      young male footballers.
AB  - Physical training is known to induce oxidative stress in individuals subjected to
      intense exercise. In this study, we investigated plasma malondialdehyde (MDA)
      levels and erythrocyte superoxide dismutase (SOD) activity of 25 young male
      footballers and a control group of similar age. Red blood cell (RBC) count,
      haemoglobin (Hb) and haematocrit (Hct) values, and copper (Cu) and zinc (Zn)
      levels were also examined. The maximal oxygen uptake (VO2max) of all subjects was
      determined in order to establish their functional capacity. The main finding of
      the present study was that plasma MDA levels, one of the most commonly used
      markers of lipid peroxidation, of this group of footballers aged under 21
      decreased slightly when compared with those of the control group (p < 0.001). In
      contrast, erythrocyte SOD activity was higher in the footballer group than in the
      controls (p < 0.001). Footballers who are under regular training showed an
      improved antioxidant activity in comparison to sedentary controls. Plasma copper
      concentration, RBC count and Hb concentration of the footballer group were all
      significantly lower than those of the control group, (p < 0.001, p < 0.01, p <
      0.01, respectively). Investigating the footballers' data with Spearman's
      correlation analyses, the correlation coefficients (r) between Zn/Cu ratio and
      SOD was positive (r=0.44; p < 0.05); and between VO2max and SOD (r=0.42; p <
      0.05) were both positive. On the basis of statistical analysis, we suggest that
      regular exercise may be beneficial in cases of oxidative damage by reducing the
      amount of lipid peroxidation and increasing the activity of the antioxidant
      enzyme SOD.

PMID- 14703605
TI  - Oxidant / antioxidant status in patients with psoriasis.
AB  - Psoriasis is a common, chronic inflammatory skin disease with unknown etiology.
      Recently it has been suggested that increased ROS production and deficient
      function of antioxidant systems activities may be involved in the pathogenesis of
      the disease. Although there are several studies investigating oxidant/antioxidant
      systems in psoriatic patients, the data obtained from these studies is not
      concordant. In this study, superoxide dismutase (SOD) enzyme activity, and
      malondialdehyde (MDA) and antioxidant potential (AOP) levels in thirty-five
      patients with psoriasis were investigated and compared with those of twenty-four
      control subjects. Clinical severity of the disease was determined according to
      the Psoriasis Area and Severity Index (PASI) scores in the patients. Plasma SOD
      activity and MDA levels were significantly higher (p=0.012 and p=0.005
      respectively), whereas AOP levels were lower, in patients than controls
      (p=0.001). There was no correlation between PASI scores and plasma SOD, MDA, and
      AOP levels. Our findings may provide some evidence for a potential role of
      increased ROS production and decreased antioxidant activity in psoriasis.

PMID- 14703606
TI  - Corrosive-induced gastric outlet obstruction.
AB  - Ten patients with gastric scarring and an outlet obstruction secondary to
      ingestion of corrosive substances were referred to our department for surgical
      management, between May 1999 and April 2003. Hydrochloric acid was the most
      common corrosive ingested (4 cases), although many were not aware of the nature
      of the ingested substance. An associated esophageal stricture was present in 5
      cases (50%). All the patients initially underwent feeding jejunostomy, with
      definitive surgery performed at a later date. A partial gastrectomy was found to
      be the most satisfactory procedure, and was performed in 90% of the cases (9
      patients).

PMID- 14703607
TI  - Mesopic contrast sensitivity functions in amblyopic children.
AB  - This study both measured and compared the mesopic contrast sensitivity function
      and the visual acuity in both normal and amblyopic eyes from amblyopic children
      using an ACV (visual acuity analyzer). Twenty one amblyopic children (mean age,
      8.48 years; S.D., 1.68 years), 11 strabismic amblyopes and 10 anisometropic
      amblyopes, were tested. Based on a display of the standard optotypes, the minimal
      contrast level, at which the optotypes were correctly read for all sizes of
      displays from a distance of 1m, was measured. The contrast ranged from 1% to 99%
      and the spatial frequencies ranged from 0.6 to- 30cpd using a Landolt ring
      composed of low (0.6- 2.9 c.p.d.), intermediate (3.0 - 12.9 c.p.d.) and high
      level (13.0- 30.0 c.p.d.) frequencies. As the visual acuity decreased, the
      mesopic contrast sensitivity function decreased along the contrast sensitivity
      axis. However, the peak sensitivity was noted at the same spatial frequencies. A
      comparison between the normal eye and the corresponding amblyopic eye showed that
      under mesopic conditions, the contrast sensitivity functions decreased more in
      the intermediate spatial frequencies than in the other spatial frequencies. The
      mesopic contrast sensitivity function decreased in the amblyopic eyes, which
      suggests the possibility of its use an adjunct to an evaluation of amblyopia.

PMID- 14703608
TI  - Detection and typing of HSV-1, HSV-2, CMV and EBV by quadruplex PCR.
AB  - The development of a multiplex polymerase chain reaction (PCR) method for rapid
      and accurate detection and typing of herpes simplex virus type 1 (HSV-1), and
      type-2 (HSV-2), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is very
      important for clinical diagnosis to allow the deliver of therapy as early as
      possible. Large scale amplifications by multiplex PCR of viral DNA can lower the
      cost and time for viral diagnosis. In this study, therefore sensitive quadruplex
      PCR was achieved by optimizing parameters such as primers, and 1.5 mM magnesium
      and 200 uM dNTPs concentrations. The concentrations of HSV-1, HSV-2, CMV and EBV
      primers were 0.5, 0.3, 0.25 and 0.25 pmoles, respectively. Optimal annealing
      temperature was 54 degrees C. Employing these conditions, we could detect 10
      copies of reconstructed template plasmid DNA, which were cloned to vectors
      containing target sequences of viral DNA. PCR products of 271 bp for HSV-1, 231
      bp for HSV-2, 368 bp for CMV, and 326 bp for EBV were separated on 5.0%
      polyacrylamide gel electrophoresis and confirmed by direct sequencing. The
      present study showed that the quadruplex PCR assay described herein has potential
      application in clinical diagnosis, when rapid, accurate detection and typing of
      viruses HSV-1, HSV-2, CMV or EBV are necessary.

PMID- 14703609
TI  - The comparison of VATS ramicotomy and VATS sympathicotomy for treating essential
      hyperhidrosis.
AB  - This study was undertaken to determine if better results could be achieved by
      comparing the results of a thoracic sympathetic ramicotomy (division of rami
      communicantes) with a conventional thoracic sympathicotomy (division of
      sympathetic trunk) for treating essential hyperhidrosis. From August 2001 to
      February 2002, 29 consecutive patients underwent surgery of the sympathetic
      nerves in order to treat severe essential hyperhidrosis. Of these patients, a
      ramicotomy was performed under VATS (VATS-R) in 13 patients, sympathicotomy under
      VATS (VATS-S) in 13, a unilateral ramicotomy and contralateral sympathicotomy
      under VATS (VATS-RS) in 2 and a sympathicotomy via a thoracotomy (T-S) in 1.
      There was no significant difference between the VATS ramicotomy group (VATS-R,
      n=13) and VATS sympathicotomy group (VATS-S, n=13) in terms of gender, pleural
      adhesions or comorbidities. However, the age of the VATS-S group at surgery was
      higher than that of the VATS-R group (p=0.050). The operation times, and hospital
      stays of the groups were 51.5 and 41.9 minutes, and 2.0 and 2.3 days,
      respectively. The recurrence rate of the operated sites according to the surgical
      methods (ramicotomy and sympathicotomy regardless of VATS) was 21.4% (6/28) in
      the ramicotomy group and 6.7% (2/30) in the sympathicotomy group, but there was
      no statistical significance (p=0.101). This study compared the dryness of the
      enervated sites and the severity of compensatory sweating among the ramicotomy
      (n=11, excluded 2 re-operated cases from 13 VATS-R), sympathicotomy (n=14, VATS-S
      13 and T-S 1) and the synchronous or metachronous ramicotomy/sympathicotomy
      groups (n=4, included 2 reoperated cases of VATS-R). The sympathicotomy group had
      an over-dryness of the enervated sites (dryness 1.4, from 1 to 3; 1:over-dried,
      2:humid, 3:persistent sweating) and complained of severe compensatory sweating
      (severity 3.5, from 1 to 4; 1:absent, 2:mild, 3:embarrassing, 4:disabling).
      However, the patients whounderwent a ramicotomy maintained some humidity of the
      enervated sites (dryness 2.0, p=0.012) and showed milder compensatory sweating
      (severity 2.7, p=0.056) than those in the sympathicotomy group. Furthermore, the
      dryness of the ramicotomy side was different from that of the sympathicotomy side
      in 3 out of 4 ramicotomy / sympathicotomy (R+S) patients (the side of the
      ramicotomy was humid and that of the sympathicotomy was over-dried). The average
      dryness and the compensatory sweating at these sites were in the midst of the two
      groups (dryness and severity 1.6 and 3.0, respectively). A ramicotomy can prevent
      over-dryness of the enervated area and decrease the severity of compensatory
      sweating through the selective division of the rami communicantes of the thoracic
      sympathetic ganglia. Postoperatively, almost all ramicotomy patients had no
      functional problems in daily life or in their occupational activity, because they
      could maintain hand humidity. Moreover, they showed no more than a mild degree of
      compensatory sweating and reported high long-term satisfaction rates. Therefore,
      a sympathetic ramicotomy rather than a conventional sympathicotomy is recommended
      as a more selective and physiologic modality for treating essential
      hyperhidrosis.

PMID- 14703610
TI  - Endothelial dysfunction and alteration of nitric oxide/ cyclic GMP pathway in
      patients with exercise-induced hypertension.
AB  - The diagnostic and prognostic implication of exaggerated blood pressure response
      to exercise have been controversial, with opinions ranging from a benign process
      to a harbinger of potential cardiovascular morbidity. Endothelial dysfunction has
      been demonstrated in patients with atherosclerosis and as a risk factor for
      coronary artery disease. However, whether the cause of exercise-induced
      hypertension might be related to endothelial dysfunction has not been well
      elucidated. We evaluated endothelial function in patients who showed a systolic
      blood pressure > or = 210 mmHg in males and > or = 190 mmHg in females during
      treadmill exercise test. We measured the endothelial function of the brachial
      artery in 35 patients with exercise-induced hypertension, and in 35 age- and
      gender-matched normal control subjects, by a high resolution ultrasound
      technique, and the concentration of NO2-/NO3- and cyclic guanosine monophosphate
      (GMP). Endothelial-dependent vasodilation was impaired in patients with
      hypertension compared to normal controls (3.14 +/- 0.61 vs. 6.5 +/- 0.76%, p <
      0.05). The extent of vasodilation was significantly correlated with age (r=-0.28,
      p < 0.05) and systolic blood pressure difference (r=-0.36, p < 0.05). The levels
      of NO2-/NO3- and cyclic GMP at maximal exercise were significantly higher than
      those at rest and recovery in both controls and the hypertensive group (p <
      0.05). Although there was no significant difference in the increment of NO2-/NO3-
      during maximal exercise between the controls and hypertensive group (55 +/- 17
      vs. 56 +/- 12 micro mol/L, p=NS), cyclic GMP level during maximal exercise was
      significantly higher in the control group than the hypertensive group (10 +/- 1.8
      vs. 8.3 +/- 2.5 pmol/ml, p 0.05). Patients with exercise-induced hypertension
      have poor endothelium-dependent vasodilation due to an impaired nitric
      oxide/cyclic GMP pathway, which may play a significant role in increasing blood
      pressure during exercise with inadequate peripheral adjustment to changing
      cardiac output.

PMID- 14703611
TI  - Tumor necrosis factor-alpha levels and promoter polymorphism in patients with
      Kawasaki disease in Korea.
AB  - Tumor necrosis factor (TNF)-alpha plays a major role in the pathogenesis of
      Kawasaki disease (KD), a systemic vasculitis primarily affecting young children.
      We performed this study to examine the serum levels of TNF-alpha and to
      investigate a possible relation to promoter polymorphism at positions -238 and 
      308 in KD patients in Korea. We obtained 48 paired serum samples from 24 patients
      in the acute and subacute stages of KD, and control sera from 12 age-matched
      children who were having routine blood samples taken before elective surgical
      procedures. Our studies showed a significant increase in serum levels of TNF
      alpha measured in the acute stage of KD (24.1 +/- 9.4 pg/mL) compared to those in
      the subacute stage (11.8 +/- 5.8 pg/mL; p < 0.01) and normal controls (10.4 +/-
      4.9 pg/mL; p < 0.01). Previous studies report that the presence of the A allele
      at positions -308 and -238 may be associated with higher TNF-alpha levels.
      However, our results showed that the frequency of the A allele at position -308
      in the KD patients was the same as the controls (2 out of 24, 8.3% vs. 8.3%, odds
      ratio (OR)= 1.00), while the frequency of the A allele at position -238 in the KD
      patients was lower than the controls (0/24, 0% vs. 8.3%, OR=0.00); this
      difference though was not statistically significant. We concluded that although
      TNF-alpha levels were significantly elevated in the acute stage of KD, there was
      no significant difference in the frequency of the A allele at positions -238 and 
      308 between the KD and control groups in Korean patients.

PMID- 14703612
TI  - Testosterone causes simultaneous decrease of [Ca2+]I and tension in rabbit
      coronary arteries: by opening voltage dependent potassium channels.
AB  - The relationship between the level of testosterone and the incidence of coronary
      heart disease is still controversial in the view of the results of clinical and
      epidemiologic studies. This uncertainty might be partly due to relatively small
      number of experimental studies undertaken to investigate the cellular mechanism
      underlying the vascular responses to testosterone. To further investigate the
      cellular mechanisms of testosterone with respect to vascular response, we
      investigated the effect of testosterone on contractility and intracellular Ca2+
      regulation in a rabbit coronary artery and evaluated the underlying mechanism of
      testosterone-induced changes of coronary vascular tone by using various
      pharmacological blockers. Testosterone was found to relax rabbit coronary
      arteries in a dose-dependent manner, and no significant difference was found in
      the relaxation response to testosterone with or without endothelium. Similar
      results were obtained in male and non-pregnant female rabbit coronary arteries.
      The relaxation response of rabbit coronary arteries to testosterone was greater
      for PGF2alpha-contracted rings than for KCl contracted rings, which suggest the
      involvement of K+ channels. Furthermore, the relaxation response to testosterone
      was significantly reduced by 4-aminopyridine, a sensitive blocker of voltage
      dependent K+ channels, but not by low doses of tetraethylammonium or iberiotoxin,
      a Ca2+ activated K+ channel blocker. Testosterone simultaneously reduced the
      intracellular Ca2+ concentration ([Ca2+]i) and tension, and 4-AP effectively
      antagonized the testosterone-induced change of [Ca2+]i and tension. Therefore, it
      may be concluded that the stimulation of voltage dependent K channels is
      responsible, at least in part, for the testosterone-induced relaxation of rabbit
      coronary arteries.

PMID- 14703613
TI  - Vocal analysis after vertical partial laryngectomy.
AB  - It is generally believed that a reconstruction of the glottic region after a
      vertical partial laryngectomy (VPL) can improve the glottic and supraglottic
      function. However, there is a paucity of reports on secondary healing without a
      glottic reconstruction after a VPL. The aim of this study was to obtain objective
      phonatory data after a VPL without a glottic reconstruction. From 1993 to 2001,
      13 patients, who had been treated with VPL without a glottic reconstruction, were
      enrolled in this study. Patients with a postoperative follow up of less than 12
      months were excluded. Seven lesions were classified as T1 glottic cancer and six
      as T2 glottic cancer- standard VPL (11 cases) and frontolateral VPL (2 cases).
      Acoustic ((fundamental frequency, Fo), jitter, shimmer, the noise to harmonic
      ratio (NHR)), aerodynamic (maximal phonation time (MPT), mean flow rate (MFR))
      analysis and videostroboscopy were performed to evaluate the voice. There were
      significant differences in the Fo, jitter, shimmer, NHR, MPT and MFR between the
      VPL group and normal control group. In videostroboscopy, the following tendencies
      were observed in many cases: incomplete glottic closure, a decreased and
      irregular mucosal wave and amplitude, supraglottic voicing, abnormal arytenoid
      movement and anterior commissure blunting. Objective phonatory data after VPL
      without a glottic reconstruction was obtained. The voice quality after a VPL
      without a glottic reconstruction was somewhat unsatisfactory. A further
      comparison with other different surgical techniques of a VPL would help determine
      a better way of improving the voice quality in these patients.

PMID- 14703614
TI  - Diagnosis of occult thyroid carcinoma by ultrasonography.
AB  - The increased sensitivity of many imaging devices has increased the
      identification of asymptomatic nodules in the thyroid gland. In this study we
      investigated the actual incidence of nonpalpable thyroid nodules and occult
      carcinoma in women. Between January and June 2003, among the women who were
      scheduled to undergo breast ultrasonography, 697 without palpable thyroid nodules
      were screened for thyroid nodules. They were classified into four categories
      according to ultrasonographic findings: negative, benign, indeterminate and
      malignant. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was carried out
      for all malignant lesions and for some of the benign and indeterminate ones. The
      nodule detection and malignancy rates were determined and the effectiveness of
      ultrasonography as a diagnostic tool was also investigated. Out of the 697
      subjects, 246 (35.3%) were found to have thyroid nodules. The malignancy
      detection rate based on the FNAB results, including both suspicious and malignant
      groups, was 3.6% (25/697) for all subjects. In addition, 3.0% (21/697) of all the
      women were confirmed to have thyroid cancer by surgery. The sensitivity of
      sonographic classification was increased from 80% to 100% when the indeterminate
      class was added to the malignant one, although this decreased the specificity
      from 91.7% to 33.3%. In conclusion, high-resolution ultrasonography detected a
      high percentage of malignant nodules. Ultrasonography can augment its value by
      guiding FNAB, in addition to providing diagnostic images.

PMID- 14703615
TI  - The use of elastic adhesive tape to promote lymphatic flow in the rabbit hind
      leg.
AB  - Any method that deforms the skin of the extremities may increase lymphatic flow
      rate, and may be applied to treat peripheral lymphedema. This study was
      undertaken to investigate whether or not elastic adhesive tape with passive
      exercise can increase lymph flow in the rabbit hind leg by effective and periodic
      skin deformation. Cannulation into a pre-popliteal afferent lymphatic vessel in
      the lower left leg of 22 male New Zealand White rabbits was performed under a
      stereomicroscope. After stabilization, lymph was collected at rest or during
      passive exercise with an electric motor at 60 r.p.m. for 15 minutes and was then
      measured. Lymph flow rate was calculated and expressed as g/hour. Increase of
      lymph flow rate due to taping was significant only for passive exercise
      (p=0.0317). The lymph flow rate increased linearly as the area of tape was
      increased (p=0.0011), and lymph flow rates were significantly different according
      to site (p=0.0017). Tape on the anterior aspect of the ankle caused salient
      deformation and tended to increase the lymph flow rate more so than tape on the
      dorsum of the foot (p=0.0831). Taping with elastic adhesive tape in passive
      exercise increased the lymph flow rate in the rabbit hind leg by deforming the
      skin, which suggests a novel therapeutic method in cases of peripheral
      lymphedema.

PMID- 14703616
TI  - The role of splenectomy in patients with hepatocellular carcinoma and secondary
      hypersplenism.
AB  - Hypersplenism, secondary to portal hypertension, is common in hepatocellular
      carcinoma (HCC) with liver cirrhosis. Hepatic resection in the patient with
      hypersplenic thrombocytopenia (HSTC) may cause a perioperative bleeding episode
      and sometimes, liver failure. In order to investigate the effect of concomitant
      splenectomy in HCC patients with HSTC, clinical parameters are retrospectively
      reviewed for 18 HCC patients who underwent hepatic resection with or without
      splenectomy. Among 581 HCC patients who underwent hepatic resection during the
      past 17 years, 18 patients with HSTC were investigated. Twelve of them underwent
      hepatic resection for HCC and had a concomitant splenectomy and the remaining 6
      patients underwent hepatic resection for HCC only. The clinical outcomes and
      postoperative changes in platelet count, serum albumin level, serum total
      bilirubin levels, prothrombin time and clinical staging (Child-Pugh
      Classification) were reviewed. The resected spleen mean weight was 350.7 +/-
      102.9 g. Postoperative platelet counts were significantly increased with albumin
      levels and clinical staging scores also improved after the splenectomy. Among the
      12 patients who had a splenectomy, 6 patients had postoperative complications and
      one died of recurrent variceal bleeding. According to this data, it is not
      harmful to perform a concomitant splenectomy and hepatectomy for the HCC patient
      with severe HSTC, it can even be beneficial in improving both the platelet count
      and clinical staging.

PMID- 14703617
TI  - Characterization of the two genes differentially expressed during development in
      human fetal astrocytes.
AB  - Astrocytes are ubiquitous in the brain and have multiple functions. It is
      becoming clear that they play an important role in monitoring the
      neuromicroenvironment, information processing, and signaling in the central
      nervous system (CNS) in normal conditions and that they respond to CNS injuries.
      During the development of the CNS, astrocytes play a key role as a substrate for
      neuronal migration and axonal growth. To identify genes that could participate in
      astrocyte maturation, we used the differential display reverse transcription-PCR
      (DDRT-PCR) method. Human fetal astrocytes were cultured and total RNAs were
      isolated at intervals of 5 days for 50 days. Using 24 primer combinations, we
      identified a set of 18 candidate cDNAs deriving from the excised DDRT-PCR bands.
      DNA sequencing revealed 16 genes that have been described already. We found that
      RTP, TG, hTM-alpha, SPARC, TRIP7, and RPL7 genes were expressed increasingly,
      while HMGCR, RPL27a, NACA, NPM, and TARBP2 genes were expressed decreasingly,
      according to their culture stages. We also found two unidentified genes, A3 and
      C8, which were expressed differently in culture stages; the former was expressed
      decreasingly and the latter increasingly. These two genes were found in the same
      amount in genomic DNA from various human cells such as astrocytes, astrocytoma,
      trophoblasts and lymphocytes. The A3 gene was found only in human genomic DNA,
      but not in rat (ATr5), mouse (RAW264.7), or monkey (Vero) cells, whereas the C8
      gene was found in human genomic DNA and monkey cells, but not in rat or mouse
      cells. We analysed these two genes for identification. There was >92% nucleotide
      sequence identity between the A3 gene (3,626 bp) and the Homo sapiens general
      transcription factor 3 (GTF3), and >96% nucleotide sequence identity between the
      C8 gene (2,401 bp) and the transmembrane receptor Unc5h2. These findings suggest
      that these two genes may participate in some functional roles within the cells.

PMID- 14703618
TI  - Postoperative liver regeneration and complication in live liver donor after
      partial hepatectomy for living donor liver transplantation.
AB  - The safety of donor is the first priority during whole procedure in living donor
      liver transplantation. We evaluated the short-term results of partial living
      donor liver transplantation in the view of donor safety. We prospectively
      evaluated the extent of liver regeneration, the recovery of liver function, and
      the perioperative complications in 41 live liver donors for partial liver
      transplantation at our institution. We developed novel personal computer
      volumetry program for the evaluation of liver regeneration. Serial CAT scan was
      performed preoperatively, at postoperative day (POD) #7 and POD #30 and liver
      volume was measure by using volumetry program. The serum level of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin
      (T.bil.) was serially monitored. There were 34 males and 7 females. The mean
      preoperative liver volume was 1320.6 cm3. The remained mean liver volume was
      687.8 cm3 after harvest, and increased to 954.4 cm3 (144.6%) at POD #7, and
      1169.5 cm3 (81.4%) at POD #30, which was 88.5% of preoperative total liver
      volume. The serum level of ALT/ AST and T.bil. peaked at POD #1 and declined
      thereafter, and finally returned to preoperative level at POD #30. The
      regeneration rate was significantly different by age, type and size of graft
      according to the donors. Six donors experienced postoperative complications and
      they were four pleural effusions, one wound infection and one case of bile duct
      stenosis that was treated by endoscopic nasal biliary drainage. All of them were
      right lobe donors. In conclusion, the donor liver regenerated up to 88.5% of
      preoperative volume with full recovery of liver function at POD #30. Right lobe
      donors suffered more complications and need more meticulous operative and
      postoperative care than left lobe or left lateral segment donors.

PMID- 14703619
TI  - Standardization of flap design for oropharyngeal reconstruction after cancer
      ablation surgery.
AB  - A variety of residual defects containing many sulci and fossae in the
      oropharyngeal cavity make it extremely difficult to achieve an adequate flap
      design as well as the functional reconstruction of the complex defects after
      ablation surgery for oropharyngeal tumors. This study attempted to standardize
      flap design for the different types of defects in order to produce a better
      functional reconstruction of intra-oral defects. The oropharyngeal defects were
      classified into 6 Zones. When the defect involves only the mouth floor, it was
      classified as Zone 1. A hemi tongue was classified as Zone 2. A defect involving
      the mouth floor and a part of the tongue was classified as Zone 3. A defect
      involving the mouth floor, a part of the tongue and the tonsil was classified as
      Zone 4. A defect involving the mouth floor, a part of the tongue, tonsil and soft
      palate was classified as Zone 5. A defect involving the pharyngeal wall was
      classified as Zone 6. The following four types of forearm free flap designs were
      applied to each defective Zone accordingly: Type I flap design - an unilobed
      design for reconstructing Zone 1, 2 and 6 defects, Type II design - bilobed
      design for reconstructing Zone 3 defects, Type III design - trilobed design for
      reconstructing Zone 4 defects and Type IV design for reconstructing Zone 5
      defects. During 1999 to 2002, 91 patients with oropharyngeal defects underwent a
      reconstruction using these standardized forearm free flap designs. The Type I
      design was used in 41 cases, the Type II design in 18 cases, the Type III design
      in 10 cases and the Type IV design in 22 cases. In all patients, the
      decannulation was successful, and the swallowing and deglutination functions were
      within the normal parameters. There was less nasal escape of the voice and the
      regurgitation of food than that observed using the conventional flap design
      method. Effective and functional reconstructions with minimal morbidities are
      possible with the application of the standardized forearm free flap design in
      oropharyngeal defects.

PMID- 14703620
TI  - Difficulty in removal of a femoral intramedullary nail: the geometry of the
      distal end of the nail.
AB  - Different difficulties can be encountered during removal of an intramedullary
      femoral nail depending partly upon the design of the nail but mainly on bone
      ingrowth. This possibility is higher in younger patients and when nail removal is
      attempted long after initial insertion. We present a case of difficult nail
      removal. The nail design appears to be important in this problem.

PMID- 14703621
TI  - Aeromonas hydrophila and aspiration pneumonia: a diverse presentation.
AB  - Although there are ever increasing reports of extraintestinal human infections
      caused by Aeromonads, in both immunocompromised and immunocompetent patients,
      respiratory tract infections remain uncommon. We describe a case of aspiration
      pneumonia in an immunocompetent patient with multiple sclerosis, caused by a
      community acquired, multidrug resistant strain of Aeromonas hydrophila sensitive
      only to meropenem. The case highlights the clinical significance of Aeromonas
      hydrophila as a respiratory pathogen, as well as the community origin of
      multidrug resistance and the utility of newer carbapenems in such cases.

PMID- 14703622
TI  - Palmar divergent dislocation of scaphoid and lunate.
AB  - A 28-year-old man presented with a palmar divergent dislocation of the scaphoid
      and lunate. He was treated with an open reduction and an internal fixation with
      two Kirschner's wires after the 25th day of trauma due to a neurological injury.
      The results were satisfactory after 18 months follow up without any evidence of
      avascular necrosis and traumatic arthritis of the scaphoid and lunate. The
      patient had no limitation in motion or intermittent wrist pain. We reported this
      case with a brief review of relevant literatures.

PMID- 14703623
TI  - Gastric ulcer perforation in heart-lung transplant patient: a successful case of
      early surgical intervention and management.
AB  - Gastrointestinal complications may follow organ transplantation. A patient who
      underwent heart lung transplantation due to patent ductus arteriosus and
      Eisenmenger's syndrome had an episode of acute cardiac rejection and was treated
      with a bolus injection of methylprednisolone followed by a high oral dose of
      prednisone. On the 22nd postoperative day, the patient complained of acute
      abdominal pain with muscular rigidity and a plain chest x-ray showed free air in
      the right subdiaphragmatic area. Under the suspicion of bowel perforation, an
      emergency laparotomy was performed and the perforated stomach had a wedge-shaped
      resection that included the perforation. Following the laparotomy, the
      postoperative course was uneventful and the patient was discharged on post
      laparotomy day 10.

PMID- 14703624
TI  - An anatomic variation of the trapezius muscle in a Korean: the cleido-occipitalis
      cervicalis.
AB  - A variation of the trapezius muscle was observed in a Korean female adult cadaver
      during routine student dissection. The lateral, upper three-fourths of the
      descending portion of the trapezius muscle were separated from the remainder of
      the muscle. This single, isolated bundle fused above the insertion of the
      midpoint of the clavicle, and attached to the clavicle as a separate tendon. The
      remaining descending portion inserted into the clavicle and scapula as usual.
      This abnormal muscle bundle is considered as a variant of the cleido-occipitalis
      cervicalis, and formation of this variation is discussed based on the
      embryological development of the relative muscular structures.

PMID- 14703625
TI  - Homonymous hemianopia after embolization of an aneurysm-associated AVM supplied
      by the anterior choroidal artery.
AB  - The primary objective for the treatment of arteriovenous malformations (AVM) of
      the brain is to reduce the risk of hemorrhage. The risk of hemorrhage is known to
      increase with the presence of an aneurysm associated with AVM. The purpose of
      this report is to describe the development of visual complications after the
      embolization of a hemorrhagic anterior choroidal artery feeding AVM with an
      associated aneurysm and to describe the possible causes.

PMID- 14703626
TI  - Radial nerve paralysis due to Kent retractor during upper abdominal operation.
AB  - After general anesthesia, peripheral nerve paralysis is a rare complication. The
      frequently damaged nerves including: branches of the brachial plexus, the ulnar,
      radial and common peroneal nerves, and sometimes the facial nerve. The radial
      nerve is the most infrequently damaged one, accounting for only 3% of nerve
      damage. We report a case of radial nerve paralysis due to self retractor during
      abdominal operation, its clinical findings, and review of the literature on
      peripheral nerve paralysis.

PMID- 14703627
TI  - A variation of the musculocutaneous nerve absent.
AB  - A variation of the brachial plexus, characterized by the absence of the
      musculocutaneous nerve on the left arm, was found during the dissection of a 28
      year old male cadaver. The whole lateral cord was joined to the median nerve,
      which it met in two points. One was a typical junction of both roots of the
      median nerve at the level of the coracoid process. The other was a junction of
      the remaining lateral cord and the median nerve, which was 92 mm away from the
      typical junction. This case provided some evidence about the absence of the
      musculocutaneous nerve, rather than a complete fusion of the median and
      musculocutaneous nerves. As the nerves are named due to their course or
      innervation, and not from their origin, it is reasonable to assume that the
      combined nerve was actually the median nerve, and that the musculocutaneous nerve
      did not exist.

PMID- 14703628
TI  - Diabetic cervical radiculopathy with adhesive capsulitis of the shoulder.
AB  - The common form of diabetic neuropathy is symmetrical peripheral polyneuropathy,
      which involves the distal part of the lower extremities whereas diabetic
      amyotrophy is seen in the proximal part of the lower extremities. Although other
      regions may also be affected, the presence of upper extremity involvement has
      rarely been emphasized. Diabetic radiculopathy may involve the cervical region
      before, after, or concurrently with lumbosacral radiculopathy. We report 2 rare
      cases of diabetic radiculopathy which involves the cervical region without
      involving the lumbosacral region. To our knowledge, these are the first reported
      cases of diabetic radiculopathy involving the cervical region only. In our cases,
      severe adhesive capsulitis in a shoulder was noticed together with cervical
      radiculopathy. Both diabetic radiculopathy and adhesive capsulitis have a poorly
      understood pathogenesis and their combined presence is presumed to be rare.
      Clinical features and management of cervical radiculopathy with adhesive shoulder
      capsulitis in 2 diabetic patients is described.

PMID- 14703630
TI  - Update on Elan vaccine for Alzheimer's disease.

PMID- 14703629
TI  - Chronic post-thrombotic obstruction of the inferior vena cava: both renal veins
      being the cause of painless gross hematuria from pelviureteral mucosal varices in
      normal functioning kidney.
AB  - A 31-year-old man presented with painless gross hematuria. His serum-creatinine
      level was within the normal range. Abdominopelvic CT showed an infrahepatic
      calcified fibrous cord, which was suggestive of inferior vena cava (IVC) remnant.
      Extensive venous collateralization around both kidneys and venous drainage of the
      extremities via the inferior epigastric and internal thoracic veins were shown.
      We report a case of chronic post-thrombotic obstruction of the IVC, involving
      both renal veins, which was believed to be the cause of painless gross hematuria
      from mucosal varices of the pelviureteral system in normal functioning kidney.

PMID- 14703631
TI  - Video-assisted anatomic mediobasal segmentectomy of lung.
AB  - Although video-assisted thoracic surgery (VATS) is now widely accepted, pulmonary
      segmentectomy is rarely performed. We present a case series of patients
      undergoing this procedure. The first patient had multiple arteriovenous
      malformations of the right mediobasal segment and a leiomyoma in the bronchus of
      the mediobasal segment. The second patient had multiple pulmonary metastases from
      colon cancer, including one in the right mediobasal segment. The third patient
      had metastases in the right ventrobasal and mediobasal segments from a solitary
      fibrous tumor that originated in the contralateral diaphragm. In the first two
      patients, a solitary mediobasal segmentectomy was done. In the third patient, a
      combined ventrobasal and mediobasal bisegmentectomy was performed. There were no
      complications, and visualization was excellent. Because VATS provides such
      excellent exposure, mediobasal segmentectomy of the lung is feasible, even though
      this operation is not done as an open procedure.

PMID- 14703632
TI  - A laparoscopic approach to small bowel obstruction secondary to endometriosis.
AB  - The complications of endometriosis are well recognized and extend beyond the
      pelvis. Gastrointestinal manifestations of this disease have been well described;
      however, reports of small bowel obstruction are rare. We describe the case of a
      44 year-old-woman who presented with high-grade small bowel obstruction secondary
      to an endometrioma. We review the epidemiology and pathology associated with this
      condition and describe a laparoscopic approach to its management.

PMID- 14703634
TI  - [Regarding the article "Dynamic radiographic study of the inferior gleno-humeral
      ligament"].

PMID- 14703633
TI  - Changes in left ventricular size during parabolic flights by two-dimensional
      echocardiography and level set method.
AB  - This study aims to evaluate changes on cardiac chambers size, induced by
      gravitational stresses. During parabolic flight, seven subjects underwent 2-D
      transthoracic echocardiography at three different gravity phases (1 Gz, 1.8 Gz,
      and 0 Gz). LV endocardial borders were detected applying a semi-automatic
      segmentation procedure based on level set methods. LV cavity area was computed
      frame-by-frame for a whole cardiac cycle during each gravity phase. Expected
      modifications in LV area with different gravity were found: at 1.8 Gz, end
      diastolic (ED) and end-systolic (ES) areas were significantly (p<0.05) reduced of
      10.7 +/- 5.4% and 21.6 +/- 11.1% respectively, compared to 1 Gz values, while
      they were increased of 11.2 +/- 5.4% and 11.1 +/- 6% during 0 Gz. Fractional area
      change was augmented of 20.9 +/- 29.1% at 1.8 Gz, while it remained unchanged at
      0 Gz, compared with 1 Gz values. Furthermore, LV filling due to atrial
      contraction was increased at 0 Gz of 39 +/- 35.6%.

PMID- 14703636
TI  - Hidden in plain sight.

PMID- 14703635
TI  - [Free flap for soft tissue loss of the limbs in trauma victims].
AB  - PURPOSE OF STUDY: We report a series of 67 free flaps performed between 1995 and
      2001 for soft tissue loss of the limbs in trauma victims. We searched for
      elements predictive of failure in order to better identify indications. MATERIAL
      AND METHODS: The series was predominantly masculine (52 men, 15 women). Mean age
      was 38.7 years (range 18-63). Thirty-four free flaps were performed on the upper
      limb and 33 on the lower limb. Trauma was caused by: direct crush with or without
      bone injury (n=23), burns (n=10), stripping (n=5), complications of open
      fractures (n=29). The free flaps were performed on day 0 (day of trauma) (n=7),
      on day 1 or 2 (n=5), from day 3 to 7 (n=12), and from day 8 to 31 (n=43).
      RESULTS: There were 19 complications: hematoma (n=2), infection (n=1), vascular
      problem (n=16), and 7 flaps were lost (10.4%). Logistic regression analysis
      demonstrated that the type of trauma and vascular complications were determinant
      factors predictive of failure. Conversely, the limb (upper versus lower), side,
      gender, age, or time from trauma to flap were not found to influence chances of
      success. DISCUSSION: Our series demonstrated that free flap repair performed in a
      trauma context for loss of soft tissues of the limbs is a relatively reliable
      surgical technique since the rate of success is similar to that reported for
      pediculated flaps. The usefulness of free flaps in the trauma setting is thus
      demonstrated, but the most appropriate modality remains to be determined. Many
      authors point out the importance of early cover to limit the risk of
      complications (osteitis, delayed bone healing). Others have not found this factor
      to be determinant. In everyday practice, emergency cover is not always possible
      and the question is whether a flap can be successful if performed late after the
      initial trauma. Our study demonstrates that the chances of success of a free flap
      are equivalent when performed early or late after trauma. CONCLUSION: Free flaps
      play an important role in achieving cover of tissue loss of the limbs. The type
      of trauma appeared to be the only factor predictive of failure.

PMID- 14703637
TI  - Fairness of home health payments for ostomy and wound care supplies questioned.

PMID- 14703639
TI  - Current awareness in prenatal diagnosis.

PMID- 14703638
TI  - GAO wants increases in CMS oversight of nursing homes.

PMID- 14703640
TI  - [Efficacy of intraosseous infusions of 0.03% sodium hypochlorite solution in
      combined therapy of patients with chronic traumatic mandibular osteomyelitis].

PMID- 14703641
TI  - [The strategy with respect for mandibular third molars in mandibular osteotomy in
      patients with combined maxillodental and facial abnormalities].

PMID- 14703643
TI  - [Universal carpal syringe].

PMID- 14703642
TI  - [Influence of the direction of light flow and technology of the composite
      application for the adhesion to hard tissues of a tooth].

PMID- 14703644
TI  - [Some aspects concerning the working conditions of dentists in organizations of
      different forms of property].

PMID- 14703645
TI  - Proceedings of the Abildgaard Symposium: Hypocalcaemia, Acidosis and Calcium
      Homeostasis. August 16-17, 2001, Frederiksberg, Denmark.

PMID- 14703646
TI  - [Veni--Vidi--Sui--Around the Anastomosis. Proceedings of the 14th Bernese
      Symposium on Surgical Technique. November 1, 2002].

PMID- 14703647
TI  - Proceedings of the Conference of the European Society of Veterinary and
      Comparative Nutrition. Sursee, Switzerland, 13-14 September 2001.

PMID- 14703648
TI  - Patient attitudes to the Internet and analysis of the potential role of a
      dedicated colorectal website -a prospective study.
AB  - BACKGROUND: The Internet has become an easily accessible source of information
      for patients and professionals alike. The purpose of this study were to: (i)
      analyse the attitudes of colorectal outpatients with regards the establishment of
      a dedicated, local colorectal website; and (ii) 'market research' the desired
      contents of such a site. METHODS: During a 4-week period, questionnaires were
      circulated among patients attending colorectal out-patient clinics in order to
      establish basic demographic data, Internet usage and investigate those areas of
      information that would be of interest. RESULTS: Over the study period, 118
      replies were received from 538 patients; 49 males (40.6%), 58 females (50.8%) and
      11 unspecified gender (8.4%). The age of respondents conformed to a normal
      distribution, centred on the 61-70-year-old age group. Of all respondents, 38
      patients (32%) used the Internet for general purposes. Nine (8% of all
      respondents, 23% of those with Internet access) had searched for information
      regarding their clinical problem. Forty-one patients (35% of those with access)
      indicated that they would use such a website, should one become available.
      CONCLUSION: Although Internet usage was relatively low amongst our patients and
      there was less interest in a potential website than has been noted in previous
      studies, we were able to identify a group of patients for whom the provision of a
      dedicated colorectal website would be of benefit and whose information
      requirements could easily be met within a website format.

PMID- 14703649
TI  - Proceedings of the Inaugural Conference: Craniofacial Imaging in the 21st
      Century. 6-9 September 2002, Pacific Grove, California, USA.

PMID- 14703650
TI  - Abstracts presented at the XII International HIV Drug Resistance Workshop: Basic
      Principles and Clinical Implications. 10-14 June 2003, Los Cabos, Mexico.

PMID- 14703651
TI  - How can handful of water assess basic laparoscopic skills?

PMID- 14703652
TI  - Fractured neck of femur in the mobile independent elderly patient: should we
      treat with total hip replacement?
AB  - PURPOSE: To report the outcome of displaced sub-capital neck of femur fractures
      in the independent elderly (>70 years) managed with total hip arthroplasty
      through a modified Hardinge approach. METHODS: Between 1998 and 2000, a surgeon
      performed a cemented hip replacement using a modified lateral approach in 36
      consecutive patients in the Hawke's Bay Regional Hospital, Hastings. Medical
      charts and out-patient follow-up clinic records were reviewed with respect to
      outcomes, with particular reference to complications. Independent review of
      functional outcome was completed at one year postsurgery using a questionnaire.
      RESULTS: At an average follow-up of 1.8 years (range, 1-3 years), no patient
      needed further surgery. One patient had died, giving a mortality rate at one year
      of 2.9%. All other medical complications were successfully treated. The overall
      prevalence of early medical complications was 43%. There were no dislocations,
      and 80% of patients had a good clinical outcome at their first follow-up.
      CONCLUSION: The modified lateral approach of Hardinge minimises the incidence of
      postoperative dislocation. However, there was a high incidence of medical
      complications and aggressive treatment of such complications was necessary, both
      preoperatively and postoperatively. The number of pre-existing medical conditions
      was a significant factor influencing patient morbidity.

PMID- 14703653
TI  - Emergency treatment of ankle fracture dislocations - a reliable technique for
      early reduction.

PMID- 14703654
TI  - Prevention of spectacle movement when operating.

PMID- 14703655
TI  - Steroid injection of the knee - is it in yet? Green's sign.

PMID- 14703656
TI  - A new hollow anal dilator.

PMID- 14703657
TI  - Displaced paediatric supracondylar fractures of the humerus - a sticky solution.

PMID- 14703658
TI  - Securing the head during shoulder surgery - a new and cost effective method.

PMID- 14703659
TI  - Proceedings of the 4th International Conference on Ticks and Tick-Borne
      Pathogens. Banff, Alberta, Canada. 21-26 July 2002.

PMID- 14703660
TI  - Abstracts of the 16th Annual Research Meeting of the Kind-Philipp-Foundation for
      Leukemia Research, 2003.

PMID- 14703661
TI  - Proceedings of the 23rd Annual Gravitational Physiology Meeting Stockholm, Sweden
      June 2-7, 2002.

PMID- 14703662
TI  - Adapting to artificial gravity (AG) at high rotational speeds.
AB  - Short-radius centrifugation offers a promising countermeasure to the adverse
      effects of prolonged weightlessness. Head movements made in a rotating
      environment elicit Coriolis effects, which seriously compromise sensory and motor
      processes. We have previously found that, contrary to common belief, participants
      can adapt to the Coriolis effects associated with single-quadrant yaw head turns
      during 23-rpm short-radius centrifugation, while maintaining their adaptation to
      stationary environments. Here, we focus on motion sickness and illusory motion,
      the most problematic subjective side effects. We present encouraging data that
      such context-specific adaptation generalizes immediately to a different
      centrifuge environment. It also generalizes quickly to Coriolis forces in the
      opposite direction. Implications for AG implementation are discussed.

PMID- 14703663
TI  - The health of the human skeletal system for weight bearing against gravity: The
      role of deloading the musculo-skeletal system in the development of
      musculoskeletal injury.
AB  - Musculo-skeletal disease is a major health problem which continues to increase in
      developed countries. A mechanism related hypothesis is presented to explain why
      most musculo-skeletal injury has an insidious onset and is not linked to a single
      traumatic event. The hypothesis predicts a close link between a dysfunction in
      the antigravity muscle system, which protects joints from injury, and the
      development of musculoskeletal disease patterns.

PMID- 14703664
TI  - Low gravity on earth by magnetic levitation of biological material.
AB  - The use of a magnetic field gradient levitation apparatus as a tool for
      investigating gravisensing mechanisms in biological systems and as a low gravity
      simulator for biological systems is described. The basic principles are
      described. Differences between its application to pure materials and the
      heterogeneous materials of biological materials are emphasized.

PMID- 14703665
TI  - Gravity: It's the law.
AB  - Based on experience in microgravity and on centrifuge induced hypergravity,
      exposure to either altered force field causes marked effects in animals and
      humans. It would seem logical that changes from unit gravity would have different
      effects depending on whether gravity is increased or decreased. Examples will be
      presented of responses to altered gravitational fields and changes in human and
      animal musculoskeletal, cardiopulmonary neurovestibular and metabolic responses.

PMID- 14703666
TI  - Influence of imaginary target on "dumping" of vestibulo-ocular reflexes and
      postural control.
AB  - Two studies explored 1) the effect of instruction set upon the well known
      "dumping" of the vestibulo-ocular (VOR) post-rotatory nystagmus long time
      constant (TC) and 2) the effect of imaginary earth-fixed targets on postural
      control. Imaginary targets do not produce dumping and do not improve postural
      stability, with or without pitch head movements.

PMID- 14703667
TI  - Gravitation biology using fish as model systems for understanding motion sickness
      susceptibility.
AB  - During the entire evolution of life on Earth, the development of all organisms
      took place under constant gravity conditions, against which they achieved
      specific countermeasures for compensation and adaptation. On this background, it
      is still an open question to which extent altered gravity such as hyper- or
      microgravity (centrifuge/spaceflight) affects the normal individual development,
      either on the systemic level of the whole organism or on the level of individual
      organs or even single cells. The present short review provides information on
      this topic, focusing on the effects of altered gravity on developing fish as
      model systems even for higher vertebrates including humans, with special emphasis
      on the effect of altered gravity on behaviour and particularly on the developing
      brain and vestibular system.

PMID- 14703668
TI  - The influence of 2.5 g exposure on the morphology of rat vestibular epithelia.
AB  - Several studies have shown that altered gravity causes changes in vestibular
      induced reflexes and behaviour, and in vestibular morphology. How the level of
      gravity affects the morphology of vestibular epithelia, however, is largely
      unknown. Vestibular epithelia of hypergravity (HG) exposed animals and control
      animals were histochemically labeled for actin and tubulin (two characteristic
      proteins for specific cytoskeletal structures in hair cells and supporting
      cells). Cellular organization, cytoskeletal structure and apical cross-sectional
      area were investigated.

PMID- 14703669
TI  - The expression of heat shock protein 70 in rat brain after +Gz exposure.
AB  - To investigate the effect of +Gz exposure on the expression and distribution of
      heat shock protein 70 (HSP70) in rat brain. METHODS: One hundred rats were
      randomly divided into control group, +2 Gz, +6 Gz and +10 Gz exposures groups.
      The +Gz group rats were exposed to +2 Gz, +4 Gz, +6 Gz and +10 Gz for 3 minute
      respectively. The expression of HSP70 in rat brain was measured by
      immunohistochemistry and West blot methods after +Gz exposure. RESULTS: There was
      no HSP70 expression in the brains of control rats. In +2, +4. and +6 Gz groups,
      HSP70 was obviously expressed in cortex, hippocampus and pyriform cortex 6 h
      after exposures, and strongly expressed 1 d after exposure, and then had a
      tendency to decrease 2 d after exposure, and returned to control level 6 d after
      exposure. The expression of HSP70 after +6 Gz exposure was the strongest in all
      +Gz groups. In +10 GZ group, HSP70 protein was only weakly expressed in pyriform
      cortex after exposure. CONCLUSIONS: +Gz exposures may cause time-dependent HSP70
      expression in rat brain.

PMID- 14703671
TI  - The influence of microgravity on the morphology of identified cerebral neurons in
      a cricket (Acheta domesticus).
AB  - Studies in cricket larvae (Acheta domesticus) revealed that descending sulfakinin
      ir-neurons (PDS-neurons) from the sensorimotor area of the brain are insensitive
      to gravity deprivation if they were exposed to microgravity after determination
      of their shape. In the project CRISP-2, we now extent these studies to answer the
      question whether neuronal proliferation or neurogenesis are affected by altered
      gravity. As indicator we use, in 1st instars, the morphology of perisulfakinin
      and CCAP immunoreactive neurons in the central nervous system which project
      towards the last abdominal ganglion, the input site of cercal gravity receptors.
      We have now completed the quantitative analysis of these neurons in 1st instars
      reared exclusively under 1g-conditions.

PMID- 14703670
TI  - Artificial gravity and functional plasticity of nerve system. L-[14C]-glutamate
      uptake by nerve terminals from rat cerebellum and cerebral hemispheres under
      hypergravity stress.
AB  - We have investigated the effects of altered gravity on the kinetic parameters of
      glutamate transport activity. We observed no differences in Km values for
      cerebellum and cerebral hemisphere nerve terminals (synaptosomes) between control
      rats- 18,2 +/- 7,6 micromoles (cerebellum), 10,7 +/- 2,5 micromoles (cerebral
      hemispheres) and animals exposed to hypergravity- 23,3 +/- 6,9 micromoles
      (cerebellum), 6,7 +/- 1,5 micromoles (cerebral hemispheres). The similarity of
      this parameter for the two studied groups of animals showed that affinity of
      glutamate transporter to substrate in cerebellum and cerebral hemispheres was not
      sensitive to hypergravity stress. The maximal velocity of L-[14C]-glutamate
      uptake (Vmax) reduced for cerebellum synaptosomes from 9,6 +/- 3,9 nmol/min/mg of
      protein in control group to 7,4 +/- 2,0 nmol/min/mg of protein in animals,
      exposed to hypergravity stress. For cerebral hemisphere synaptosomes the maximal
      velocity significantly decreased from 12,5 +/- 3,2 nmol/min/mg of protein to 5,6
      +/- 0,9 nmol/min/mg of protein, respectively.

PMID- 14703672
TI  - Susceptibility to motion sickness in fish: a parabolic aircraft flight study.
AB  - Juvenile swordtail fish and larval cichlids were subjected to parabolic aircraft
      flights (PAFs) and individually observed. After the PAFs, inner ear otoliths and
      sensory epithelia were examined on the light microscopical level. Otolith
      asymmetry (differences in otolith size between the left and the right side) was
      especially pronounced in those fish, who exhibited a kinetotic behaviour (e.g.,
      spinning movements) during microgravity. This speaks in favour of a theoretical
      concept according to which susceptibility to space motion sickness in humans may
      be based on asymmetric inner ear stones. The cell density of sensory epithelia
      was lower in kinetotic animals as compared to normally swimming fish. Thus,
      asymmetric otoliths can cause kinetosis in fish during PAFs, but susceptibility
      to kinetosis may also be based on an aberrative inner ear morphology.

PMID- 14703673
TI  - Visual function after prolonged bed rest.
AB  - The present study evaluated the claim of earlier reports, that of bed rest
      induced alterations in visual function. Indices of visual function were studied
      in 10 healthy male subjects, during 35 days of horizontal bed rest. Before and
      after the 35 day bed rest, both eyes of all subjects were examined for visual
      acuity, intraocular pressure, contrast sensitivity, stereopsis and visual field.
      Pre- and post-bed rest values were compared with Student's T-test. There were no
      significant differences in any of the measured indices of visual function.

PMID- 14703674
TI  - Cerebral lateralization for motor tasks in simulated microgravity a transcranial
      Doppler technique for astronauts.
AB  - In Space, central cognitive operations are unaffected but humans are slower in
      perceptual-motor performance. Transcranial Doppler ultrasonography was used to
      monitor blood flow velocity in both middle cerebral arteries during unilateral
      and bilateral fingers' movements before, during and after -6 degrees 24 hours of
      head-down tilt (HDT) in 14 (8 males and 6 females) subjects. Physiologic
      hemisphere dominance was assessed by breath-holding test. There was a significant
      main effect of motor task, F(4, 328) = 16.05, p<0.00000001, MSe = 48.2. There was
      a gender vs head-position interaction F(3,246) = 4.90 p<0.002) MSe = 120. At pre
      HDT females were right lateralized and males were left lateralized. A left shift
      in lateralization pattern was seen during 24hrs-HDT for both genders. There was a
      significant main effect of breath-holding test and a breath-holding test vs head
      position vs motor task interaction. HDT alters cerebral lateralization for motor
      control and this may be responsible for slowing in perceptual-motor performance
      in Space. TCD monitoring may be required for motor performance tasks in Space.

PMID- 14703675
TI  - Histological study of brain in the rats exposed to 93-days' tail-suspension.
AB  - Antiorthostatic position of rats during 93-days' tail suspension induced in the
      brain strongly pronounced edema of nervous tissue, alteration of structure in
      horoid plexus, pointing out the decrease in liquor secretion by exocytosis and
      increase in itraventricular pressure, morphological changes in veins and
      capillaries, reflecting the development of plethora in veins and tendency to
      thrombogenesis, and also the appearance of structural signs of prolonged arterial
      vasoconstriction and narrowing of arterial lumen in surface arteries which be
      considered as an adaptive process lying the obstacles to excessive blood inflow
      to brain and dumping the pulse wave during prolonged antiorthostatic state.

PMID- 14703676
TI  - Neuronal regulation of otolith growth and kinetotic behaviour.
AB  - Inner ear stones (otoliths) of larval cichlid fish were labelled with the calcium
      tracer alizarin-complexone (AC) before animals were subjected to hypergravity
      (hg; 3 g). After the experiment, the otoliths' area between the two AC-labellings
      was measured. Growth of hg-otoliths was significantly slowed down as compared to
      1 g-control specimens. In the course of a second experiment, the vestibular nerve
      was unilaterally transacted in neonate swordtail fish which were subsequently
      incubated in AC. Incorporation of AC was considerably lower in the otoliths of
      the transacted side. The results strongly suggest that otolith growth is
      continuously regulated in dependence of the environmental gravity vector. Since
      the otolithic calcium incorporation ceased on the transected head sides, it is
      concluded that the regulation of otolith growth is based on the central nervous
      efferent vestibular system.

PMID- 14703677
TI  - Neurobehavioural responses to hypergravity environment in the CD-1 mouse.
AB  - Behavioural responses of CD-1 mice exposed to 2 g hypergravity (HG; 60 or 120
      min) were investigated during adolescence and at adulthood. To characterise
      motion sickness (MS), pica behaviour, a reliable MS index measured through kaolin
      consumption, and spontaneous activity were evaluated before, during and after HG
      exposure. Short- and/or long-lasting effects on emotional responses, exploratory
      behaviour and spatial learning performances were also investigated and brain
      levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)
      assessed. An increased pica behaviour during post rotational days and a reduction
      in spontaneous activity during rotation indicated a mild sickness associated with
      HG, and susceptibility to MS was sex and age related. Short- and long-lasting
      effects of exposure were also observed, rotated mice showing altered
      emotional/anxiety behavioural profiles and impaired spatial learning
      performances. Moreover, central NGF levels were markedly increased after
      rotation, while minor changes were observed in BDNF levels.

PMID- 14703678
TI  - Gravity induced postponed potentiation as a result of repeated 2 G influence on
      rats.
AB  - On the base of electron- and light microscopical, immunocytochemical and
      morphometrical studies it was found that repeated 5-days' 2 G influence on the
      rats induced in the cells of the brain, pituitary and thyroid the alteration of
      structure, enzyme and hormone content which differed in quantity or quality from
      the changes arisen under the primary 5-days' 2 G and directed to increase in
      effectiveness of neuronal circuit, facilitation of synaptic transmission and
      elevation of hormone production. These structural and metabolic changes point out
      the animal capability for memorizing the change of gravity level and can be
      considered as an evidence of arise, hypergravity induced postponed potentiation
      that characterized the functional state of studied systems and presumably the
      functional state of whole organism which repeatedly was in the state of increased
      weightness.

PMID- 14703679
TI  - Gravity sensing in the central nervous system.
AB  - For human based space research it is of high importance to understand the
      influence of gravity on the properties of the central nervous system (CNS). Until
      now it is not much known about how neuronal tissue can sense gravity. The aim of
      this study was to find out weather and how the CNS, as a complex system, can
      percept and react to changes in gravity. Neuronal tissue and especially the CNS
      fulfils all the requirements for excitable media. Consequently, self
      organisation, pattern formation and propagating excitation waves as typical
      events of excitable media have been observed in such tissue. The spreading
      depression (SD), an excitation depression wave is the most obvious and best
      described of these phenomena in the CNS. In our experiments we showed that the
      properties of the SD and therefore the CNS in its properties as an excitable
      medium reacts very sensitive to changes in gravity.

PMID- 14703680
TI  - Influence of hypergravity on hypothalamic vasopressin and oxytocin neurons in
      rats.
AB  - This study was aimed to evaluate the reaction of the vasopressin (VP) and
      oxytocin (OT) neurons of the supraoptic nucleus (SON) in rats to single or
      repeated hypergravity (HG). Special attention was paid to the tyrosine
      hydroxylase (TH) expression in VP neurons as a marker of the neuron activation.
      Rats were revolved in a centrifuge with overloading 2G for 5 days or 34 days as
      well as for 34 days plus 5 days with an interval of 39 days between two
      rotations. Control rats were kept in a centrifuge room. Radioimmununoassay,
      quantitative and semi-quantitative immunocytochemistry and in situ hybridization
      were used to evaluate: a) VP concentration in the pituitary posterior lobe (PL)
      and in plasma; b) the number of VP-, OT- and TH-immunoreactive neurons in the
      SON; c) the optic density of VP-, OT- and TH-immunoreactive materials in cell
      bodies (SON) and distal axons (PL), d) the optic density of VP and OT mRNAs
      signals (S35) in the whole SON on microfilms. According to our data, VP neurons
      were strongly activated during HG (5 days or 34 days) that was manifested in the
      functional hypertrophy of the neurons, greatly increased concentrations of VP
      mRNA in the SON and VP in plasma, the onset of the TH expression. The neurons
      showed initially (5 days) the functional insufficiency (VP release > VP
      synthesis) followed by their adaptation (subsequent 29 days) to the increased
      need in VP (VP release < VP synthesis). No reaction of VP neurons was observed to
      repeated HG. In contrast to VP neurons, OT neurons did not react to short-term HG
      or showed functional depression after the long-term treatment.

PMID- 14703681
TI  - Evaluating object distance: implication for space research.

PMID- 14703682
TI  - Effects of gravity and hydrostatic pressure on angular acceleration coding
      sensory neurones in the crab and dogfish.

PMID- 14703683
TI  - The effects of a change in gravity on the dynamics of prehension.
AB  - The objective of this study was to measure the forces applied on an object
      manipulated in different gravitational fields attained during parabolic flights.
      Eight subjects participated flights (ES) and four were inexperienced (NES). They
      had to move continuously an instrumented object up and down in three different
      gravitational conditions (1 g, 1.8 g, 0 g). In 1 g, the grip force precisely
      anticipated the fluctuations of load force which was maximum and minimum at the
      bottom and at the top of the arm trajectory respectively. When the gravity
      changed (0 g and 1.8 g), the grip-load force coupling persisted for all the
      subjects from the first parabola. While the ES immediately exerted a grip force
      appropriate to the gravity, the NES dramatically increased their grip when faced
      with hyper and microgravity for the first time. Then, they progressively released
      their grip until a continuous grip-load force relationship with regard to 1 g was
      established after the fifth parabola. We suggest that each new gravitational
      field is rapidly incorporated into an internal model within the CNS which can
      then be reused as required by the occasion.

PMID- 14703684
TI  - Research in differential adaptations of vessels to microgravity.
AB  - The primary goal of this presentation is to look back to review the work on
      differential adaptation of vessels to microgravity in the past and to look
      forward to the future for research opportunities in this field. The main part is
      devoted to a discussion on the local renin-angiotensin system and ion channel
      mechanisms involved.

PMID- 14703685
TI  - Role of opioid delta1 receptors, mitochondrial K(ATP) channels, and protein
      kinase C during cardiocyte apoptosis.

PMID- 14703686
TI  - B-type natriuretic peptide and multimarker approaches in cardiovascular medicine.

PMID- 14703687
TI  - [Microcirculation in patients with chronic ischemia of the lower limbs].

PMID- 14703688
TI  - Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical
      haemochromatosis initially diagnosed by phenotypic methods.
AB  - AIM: To assess the frequency of the C282Y and H63D mutations on the HFE gene in
      Danish patients with clinical hereditary haemochromatosis initially diagnosed by
      phenotypic methods. METHODS: In the period 1950-1985, an epidemiological survey
      in Denmark identified 179 patients with clinical idiopathic haemochromatosis
      diagnosed by phenotypic methods (serum transferrin saturation, serum ferritin,
      liver biopsy and mobilisable body iron stores). In 32 unrelated patients, frozen
      blood samples were available for genetic analysis. In a subsequent series of 26
      unrelated Danish patients, a phenotypic diagnosis of clinical idiopathic
      haemochromatosis was made before blood samples were taken for HFE genotyping. The
      total series consisted of 58 patients (40 men and 18 women) with a median age of
      60 yrs (range 18-74). HFE genotyping was performed by the polymerase chain
      reaction (PCR) technique. RESULTS: Among the patients, 55 of 58 (94.8%) were
      C282Y/C282Y homozygous. One 63-year-old woman (1.7%) was compound C282Y/H63D
      heterozygous. Two women (3.4%), aged 42 and 43 yrs were negative for both the
      C282Y and the H63D mutation. CONCLUSION: In the Danish population, homozygosity
      for the C282Y mutation appears to be the prevailing cause of clinically overt
      genetic haemochromatosis. This finding has implications both for the evaluation
      of patients with iron overload disorders and for the strategy in future
      population screening surveys.

PMID- 14703689
TI  - Frequency of HFE gene mutations in Iranian beta-thalassaemia minor patients.
AB  - OBJECTIVES: Beta-thalassaemia minor (BTM) alone does not lead to iron overload,
      however, some gene modifiers and acquired causes are reported. When it is
      inherited together with a mutation in the HFE (HLA-H) gene associated with
      hereditary haemochromatosis, iron overload may ensue. To analyse the relationship
      between iron status and HFE mutations in Iranian BTM patients, we compared the
      frequency of the C282Y and H63D HFE mutations and ferritin level in a group of
      BTM patients from the National Thalassaemia Transfusion and Care Centre with that
      of healthy individuals. PATIENTS AND METHODS: Ninety-three (56 females)
      documented BTM cases and 104 (54 females) controls were enrolled in the study.
      Serum ferritin level was measured in all subjects by immuno-radiometric assay and
      HFE genotypes were determined using restriction fragment length polymorphism
      analysis of PCR-amplified HFE gene fragment. RESULTS: Eighteen (19.4%) BTM
      patients vs. 12 (11.5%) controls were H63D heterozygotes, while there were three
      (3.2%) cases and three (2.9%) controls with H63D homozygosity. All three C282Y
      mutations were found in BMT patients with one of them being a compound
      heterozygote. A significant difference was observed in the total number of HFE
      mutations in favour of BTM patients over the controls (P < 0.05, OR = 2.064). The
      H63D and C282Y allele frequencies were 12.9 and 1.61 in patients and 8.65 and 0
      in controls, respectively. The mean ferritin level in cases with HFE mutations
      showed no significant difference from that of the patients without mutations (P >
      0.05). CONCLUSIONS: Our results suggest that HFE mutations C282Y and H63D are
      more frequent in Iranian BTM patients than in the normal population, causing no
      significant changes in serum ferritin level.

PMID- 14703690
TI  - The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced
      apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis.
AB  - Many hematopoietic cells undergo apoptosis when deprived of specific cytokines.
      Lipocalin 24p3, reported to be induced in hematopoietic cells by interleukin 3
      (IL-3) depletion, induces hematopoietic cell apoptosis despite the presence of IL
      3. As granulocyte colony stimulating factor (G-CSF) depletion also induces the
      apoptosis of G-CSF-dependent cell line cells, we examined the effect of 24p3 on
      the apoptotic function induced by G-CSF depletion. 24p3 was induced by the
      depletion of IL-3, but not G-CSF, in cytokine-dependent cell lines. Although 24p3
      suppressed growth induced by IL-3, it did not influence G-CSF-dependent cell
      growth. These observations show that 24p3 is not involved in the G-CSF withdrawal
      induced apoptosis, although it is essential in IL-3 withdrawal-induced apoptosis.

PMID- 14703691
TI  - Analysis of the mechanism of action of the Brazilian type (Agamma-195 C --> G) of
      hereditary persistence of fetal hemoglobin.
AB  - We report an in vitro expression study of the Agamma-globin gene promoter
      containing the Agamma-195 C --> G mutation that causes the Brazilian type of
      hereditary persistence of fetal hemoglobin (HPFH). To demonstrate that this
      mutation results in increased promoter strength, we evaluated the mutant promoter
      linked to the hypersensitive site-2 of the locus control region with the
      luciferase reporter gene system and examined protein interactions by
      eletrophoretic mobility shift assay. The transient expression was studied in
      three cell lines: K562, HEL and 293, and indicated increased promoter activity of
      the promoter containing the Brazilian mutation in all cell lines. The protein-DNA
      interaction showed that, in contrast to the Agamma-198 T --> C mutation which has
      increased affinity for the Sp1 protein and creates a motif that behaves like a
      novel CACCC box in the gamma promoter, the Brazilian HPFH mutation decreases the
      affinity at the Sp1 protein and does not act as a CACCC motif. These results
      suggest that this mutation may act to increase the Agamma-globin chain
      production. In addition, the mechanism by which this increased production occurs
      is different to that of the -198 mutation. Other proteins may be involved in the
      overexpression of the gamma-globin chain and/or may be dependent upon the DNA
      structure.

PMID- 14703692
TI  - Effect of interleukin-15 on anti-CD3/anti-CD28 induced apoptosis of umbilical
      cord blood CD4+ T cells.
AB  - OBJECTIVES: Interleukin-15 (IL-15) has potential therapeutic advantage for
      patients receiving umbilical cord blood (CB) transplantation. The present study
      aims to examine the ability of IL-15 to modulate the survival, maturation, and
      function of anti-CD3/anti-CD28 stimulated CB CD4+ T cells, in comparison with
      responses from adult peripheral blood (APB) CD4+ T cells. METHODS: Enriched CB
      and APB CD4+ T cells were stimulated with anti-CD3 and anti-CD28 (anti-CD3/anti
      CD28) in the presence or absence of IL-15 (10 ng/mL) for 5 d. The percentages of
      apoptotic cells were assessed by propidium iodide/annexin-V flow cytometric
      staining. T-cell activation was analyzed with the expression of surface markers
      (CD45RO/CD69/CD25). Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha) production in culture supernatant was determined by enzyme-linked
      immunosorbent assay. RESULTS: CB CD4+ T cells had a higher survival and lower
      apoptotic response following anti-CD3/anti-CD28 stimulation, compared with APB
      CD4+ T cells. IL-15 enhanced apoptosis and promoted CD45RO conversion of anti
      CD3/anti-CD28 activated CB CD4+ T cells, an effect not observed with APB CD4+ T
      cells. Although activated CB CD4+ T cells expressed comparable level of CD69/CD25
      expression to adults, IFN-gamma production of activated CB CD4+ T cells was
      markedly deficient compared with that of corresponding APB CD4+ T cells.
      Exogenous IL-15 further enhanced the production of IFN-gamma, but not TNF-alpha,
      of activated CB CD4+ T cells. CONCLUSIONS: IL-15 preferentially resulted in an
      activation-enhancing effect on CB CD4+ T cells, accompanied by increased
      apoptosis. Our finding may have therapeutic implications while designing IL-15
      immunotherapy for patients receiving CB transplant.

PMID- 14703693
TI  - Structural aberrations of chromosomes 17 and 12 in chronic B-cell disorders.
AB  - OBJECTIVES: Genomic aberrations can now be identified in approximately 80% of
      chronic lymphocytic leukemia, small lymphocytic lymphoma (CLL/SLL) patients. In
      the present study, four new structural changes involving chromosomes 17 and 12 in
      CLL/SLL patients are described. METHODS: Five patients were selected for
      inclusion in the present report among a total of 92 cases with diagnosis of
      CLL/SLL. Cytogenetic studies and fluorescence in situ hybridization (FISH)
      analysis to detect some of the most frequent cryptic aberrations occurring in
      CLL/SLL patients were performed. Clinical studies are also described. RESULTS:
      Four cases showed structural rearrangements of chromosome 17. A psu
      dic(17;2)(p11.2;p21), leading to p53 deletion, was observed in a patient who
      developed a mixed cellularity Hodgkin's disease coexisting with the CLL/SLL in
      the same lymph node. Epstein Barr virus was detected in the Reed-Sternberg cells.
      Two cases had a balanced translocation t(2;17)(p21;q23). Both patients showed
      trisomy 12 and clonal evolution and one of them also had 11q deletion. In
      addition, a der(17)t(12;17)(q13;q25) as a part of a complex karyotype, and a
      complex translocation t(5;12;19) (q15;p11;q13) were also found. Four patients had
      an adverse clinical outcome and died because of disease progression. CONCLUSIONS:
      Four unreported nonrandom chromosome aberrations in CLL/SLL patients, one of them
      who might represent a new recurrent abnormality, are described. These uncommon
      abnormalities, mostly associated with evolving disease, may have implications for
      the understanding of genetic events associated with disease progression in this
      pathology.

PMID- 14703694
TI  - Interactions between the leukaemia-associated ETO homologues of nuclear repressor
      proteins.
AB  - The eight-twenty-one (ETO) homologues, represented by ETO, myeloid transforming
      gene-related protein 1 (MTGR1) and myeloid transforming gene chromosome 16
      (MTG16), are nuclear repressor proteins. ETO is part of the fusion protein acute
      myeloid leukaemia (AML)1-ETO, resulting from the translocation (8;21). Similarly,
      MTG16 is disrupted to become part of AML1/MTG16 in t(16;21). The aberrant
      expression of these chimeras could affect interplay between ETO homologues and
      contribute to the leukaemogenic process. We investigated possible interactions
      between the ETO homologues. Ectopic co-expression in COS-cells resulted in
      heterodimerisation of the various ETO homologues suggesting that they may co
      operate. Similarly, the chimeric oncoprotein AML1-ETO interacted with both MTGR1
      and MTG16. However, results from cell lines endogenously expressing more than one
      ETO homologue did not demonstrate co-precipitation. Results from IP-Western and
      size determination by gel filtration of deletion mutants expressed in COS-cells,
      indicated an important role of the HHR domain for oligomerisation. A role was
      also suggested for the Nervy domain in the homologue interactions. Our results
      suggest that ETO homologues can interact with each other as well as with AML1
      ETO, although it is unclear as to what extent these interactions occur in vivo.

PMID- 14703695
TI  - Flavones inhibit proliferation and increase mediator content in human leukemic
      mast cells (HMC-1).
AB  - OBJECTIVE: Mast cells are involved in allergic and inflammatory reactions. These
      cells are also increased in the bone marrow, skin, and other organs in systemic
      mastocytosis. Flavonoids are naturally occurring molecules with antioxidant,
      cytoprotective, and anti-inflammatory activities. Some flavonoids, like
      quercetin, inhibit the growth of certain malignant cells in culture. Quercetin
      also inhibits histamine release and induces accumulation of secretory granules in
      rat basophilic leukemia cells. METHOD: We investigated the effect of five
      flavonoids: flavone, kaempferol, morin, myricetin, and quercetin at 1, 10, and
      100 microM on proliferation and secretory mediator content (beta-hexosaminidase,
      histamine, and tryptase) in human leukemic mast cells (HMC-1), the doubling time
      of which was about 2 d. RESULTS: Flavone and kaempferol at 100 microM inhibited
      cell proliferation over 80% on either day 3, 4, or 5 of culture. Quercetin showed
      this level of inhibition only on day 5, myricetin inhibited by 50% at days 3-5,
      whereas morin's inhibition was < 20%. All flavonoids (except morin) at 100 microm
      increased histamine and tryptase content, but not beta-hexosaminidase, equally at
      days 3 and 4 of culture quercetin also increased the development of secretory
      granules. CONCLUSION: These results indicate that certain flavonoids can inhibit
      HMC-1 proliferation, induce secretory granule development and the accumulation of
      mediators.

PMID- 14703696
TI  - First case of immune-mediated haemolytic anaemia associated to imatinib mesylate.
AB  - Imatinib mesylate is a specific inhibitor of protein tyrosine kinase activity
      secondary to bcr-abl, mostly indicated for the treatment of patients with
      Philadelphia chromosome positive chronic myeloid leukaemia (CML). Generally, the
      undesirable effects of imatinib administration observed in clinical trials were
      of mild-to-moderate degree, and no haemolysis has been associated with this drug.
      We report here a case of immune-mediated haemolytic anaemia associated to
      imatinib mesylate successfully treated with prednisone in a patient with CML.
      Laboratory investigation showed anaemia [haemoglobin (Hb) of 59 g/L],
      reticulocyte of 61 x 10(9)/L and a positive direct antiglobulin test. Anti-drug
      in vitro studies revealed a positive result with gel microcolumn assay by an
      adsorption mechanism. Seventy-four days after prednisone therapy, the patient's
      Hb level was of 110 g/L with negative direct antiglobulin test and drug in vitro
      studies. This case demonstrated that patients treated with imatinib mesylate can
      present immune-mediated haemolysis and adequate management of this event can be
      done maintaining the drug and associating corticosteroids.

PMID- 14703697
TI  - Lymphoma complicating common variable immunodeficiency with granulomatous
      disease: report of two cases.
AB  - Common variable immunodeficiency (CVID) is a primary defect that is characterized
      by impaired antibody production. CVID patients may develop recurrent infections,
      autoimmune disorders and/or systemic granulomatosis. It is well documented that
      CVID patients are at risk to develop malignant lymphomas. However, to the best of
      our knowledge, lymphoma complicating the course of CVID associated with systemic
      granulomatosis has never been reported. We describe two CVID patients with
      systemic granulomatosis who developed B-cell lymphomas, one related to Epstein
      Barr virus infection, 5 and 12 yr after CVID had been diagnosed.

PMID- 14703698
TI  - Necrotising dermatitis in refractory acute myeloid leukaemia.
AB  - Severe cutaneous infections in leukaemic patients are difficult to treat and can
      rapidly become fatal. We report on a case of essential thrombocythemia evolved to
      a myelodysplastic syndrome and finally, to an overt myeloid leukaemia, refractory
      to chemotherapy. In the presence of a marked neutropenia, the patients developed
      a wide Staphylococcus epidermidis necrotising dermatitis. The diagnosis was made
      possible only by a skin biopsy culture and the antibiotic treatment, based on
      antimicrobial susceptibility tests, rapidly resolved the infection. In
      neutropenic patients, appropriate laboratory tests and treatment, can lead to
      recovery of life-threatening infections.

PMID- 14703699
TI  - Spontaneous evolution of essential thrombocythaemia into acute megakaryoblastic
      leukaemia with trisomy 8, trisomy 21 and cutaneous involvement.
AB  - Spontaneous transformation of essential thrombocythaemia (ET) into acute
      leukaemia is rare. We describe a case of ET that spontaneously transformed after
      19 yrs uneventful follow-up into acute megakaryoblastic leukaemia. Cytogenetic
      analysis of bone marrow nucleated cells showed trisomy 8 and trisomy 21 at time
      of leukaemic transformation supporting the hypothesis that chromosomal
      abnormalities are part of the mechanism that drives the leukaemic progression
      independently of drug cytotoxicity. In addition, the very rare and intriguing
      finding of M7 FAB subtype evolution of ET was complicated by cutaneous
      involvement in the leukaemic process.

PMID- 14703700
TI  - Is ibandronate effective in multiple myeloma?

PMID- 14703701
TI  - Fatal toxic bone marrow failure associated with clopidogrel.

PMID- 14703702
TI  - Current state of and outlook for organogenesis from undifferentiated cells.
AB  - PURPOSE: The aims of regenerative medicine and artificial internal organ
      development are, respectively, to regenerate and provide for transplant tissue or
      organs. METHODS: We summarize recent research on tissue differentiation and
      organogenesis using stem cells and report our laboratory's research using
      amphibian undifferentiated cells. RESULTS: We have successfully induced
      differentiation in cells from Xenopus laevis and generated structures in vitro
      that function in a similar way to organs when transplanted to Xenopus and newt
      embryos. We are attempting to establish a system to induce sensory organs,
      including eyes. CONCLUSION: Our experimental systems in amphibians are useful for
      organogenetic research, and it is hoped that our techniques can, in the future,
      be applied to mammals.

PMID- 14703703
TI  - Detailed criteria for the assessment of clinical symptoms in a new murine model
      of severe allergic conjunctivitis.
AB  - PURPOSE: The aims of this research were to: (1) generate a rapid protocol for the
      sensitization of rodents to a defined allergen without footpad injections yet
      leading to both acute- and late-phase hypersensitivity reactions in the ocular
      surface; and (2) define detailed criteria for the assessment of clinical symptoms
      in the acute-phase response. METHODS: With the approved methods for the use of
      experimental animals in research and existing sensitization protocols as a
      starting point, we developed and tested a new protocol with respect to its
      ability to generate an acute- and late-phase response on ocular challenge.
      Clinical symptoms were assessed by a trained ophthalmologist under masked
      conditions, and late-phase responses determined by histologic analysis of
      conjunctival tissue sections. RESULTS: A new protocol for the rapid sensitization
      of mice, avoiding footpad injections, yet yielding both acute- and late-phase
      allergic responses, was developed. Detailed criteria for the assessment of
      disease severity were established and tested. CONCLUSION: This protocol
      establishes a murine model of allergic conjunctivitis that will be useful for
      both the study of the molecular and cellular basis of allergic reactions in the
      ocular surface and the testing of new therapies for this disease.

PMID- 14703704
TI  - Dry eye as a major complication associated with chronic graft-versus-host disease
      after hematopoietic stem cell transplantation.
AB  - PURPOSE: To review the condition of dry eye associated with chronic graft-versus
      host disease (GVHD). METHODS: The immunopathogenic processes and therapeutic
      options for lacrimal gland chronic GVHD are discussed. RESULTS: Dry eye is the
      most frequent ocular complication after hematopoietic stem cell transplantation.
      The condition typically occurs around 6 months post-operation and is recognized
      as a complication of chronic GVHD. Lacrimal gland specimens from patients with
      dry eye show prominent fibrosis and an increase in CD34+ stromal fibroblasts in
      the glandular interstitium in addition to infiltration of T cells into the
      periductal areas. In periductal areas, CD4+ and CD8+ T cells colocalize with
      stromal fibroblasts that express the full component of surface molecules
      necessary for antigen presentation. These findings strongly suggest that
      periductal fibroblasts are involved in fibrogenic and immune processes by
      interacting with T cells in the lacrimal gland of patients with chronic GVHD,
      resulting in rapidly progressive dry eye. Current therapies for dry eye related
      to chronic GVHD include tear supplements and nonspecific immunosuppressants.
      CONCLUSION: We report a significant role for stromal fibroblasts in the
      pathogenic processes of dry eye related to chronic GVHD. Although several
      supportive therapies can reduce the symptoms, specific therapies that suppress
      fibrotic and immune processes in the lacrimal glands are necessary to control dry
      eye associated with chronic GVHD.

PMID- 14703705
TI  - Tissue engineering of the cornea.
AB  - Tissue engineering of the cornea represents a paradigm shift in medical treatment
      to overcome the present disadvantages of corneal transplantation, primarily
      immune rejection and the shortage of donor corneas. Transplantation of cultivated
      corneal epithelial cells expanded ex vivo from corneal epithelial stem cells has
      been developed and has already entered the clinical realm. However, there remain
      many hurdles to be overcome. The author and colleagues are developing a method to
      transplant cultivated cell sheets that uses a temperature-responsive culture
      dish. This article reviews the present situation regarding tissue-engineered
      corneal epithelium and introduces the results of this program of research.

PMID- 14703706
TI  - Interaction between injured corneal epithelial cells and stromal cells.
AB  - PURPOSE: To review the effects of injured corneal epithelial cells on
      myofibroblastic cell formation in corneal stroma after excimer laser surgery.
      METHODS: Denudation of epithelium alone, photorefractive keratectomy (PRK), laser
      in situ keratomileusis (LASIK), and LASIK with denudation of epithelium were
      performed in rabbit eyes. Postoperative anterior stromal haze was assessed using
      a standard scale. Immunohistochemical methods were used to detect alpha-smooth
      muscle actin (alpha-SMA), a marker of myofibroblastic cells, and type III
      collagen in subepithelial corneal tissue. Rabbit corneal fibroblasts were
      cultured on collagen gels with or without cocultured corneal epithelial cells, or
      with partially scraped epithelial cells, on a companion plate separated by a
      permeable membrane. Gel thickness was measured daily to evaluate fibroblast
      induced gel contraction. The total number of fibroblasts per gel was determined.
      Myofibroblasts were counted using immunocytochemical identification with alpha
      SMA. Transforming growth factor (TGF)-beta was assayed in media on days 3 and 6;
      these procedures were also carried out in the presence of anti-TGF-beta antibody.
      RESULTS: Three weeks after surgery, the presence of alpha-SMA-positive long
      extended and spindle-shaped stromal cells as well as synthesis of type III
      collagen were observed in the subepithelial stromal layer, corresponding to
      corneal haze, in eyes that underwent PRK and LASIK with denudation of epithelium,
      but not in those that underwent denudation of epithelium alone or LASIK. Gel
      contraction, number of alpha-SMA-positive cells, and total cell number were
      significantly greater on gels with injured epithelial cells than on those without
      epithelial cells or with uninjured epithelial cells, as was TGF-beta
      concentration in media. Anti-TGF-beta antibody eliminated these differences.
      CONCLUSIONS: The intact corneal epithelium might play an important role in
      curbing differentiation of myofibroblasts in corneal wound healing. Injured
      epithelial cells stimulate fibroblast myodifferentiation through one or more
      soluble factors, including TGF-beta.

PMID- 14703707
TI  - Substance P in human tears.
AB  - PURPOSE: To determine the levels and biochemical characteristics of substance P
      like immunoreactivity (SPLI) in human tears and ascertain whether substance P
      (SP) concentrations in tears reflect the condition of the ocular surface.
      METHODS: Unstimulated tears were collected with a micropipette. Tear samples were
      partially purified using C-18 cartridges. Levels of SPLI in purified samples were
      measured using an enzyme immunoassay (EIA). For biochemical characterization of
      SPLI, tear extracts were fractionated using high-performance liquid
      chromatography (HPLC); each fraction was then subjected to EIA. To determine the
      catabolism of SP in tears, synthetic SP was incubated in medium containing pooled
      tears and then analyzed using HPLC. RESULTS: The concentration of SPLI in normal
      human tears was 306.0 +/- 96.5 pg/mL (mean +/- SD, range 148-555 pg/mL). Levels
      of SPLI did not vary significantly by age or gender. Concentrations of SPLI in
      tears from eyes with unilateral corneal hypesthesia were lower than those in
      tears from contralateral healthy eyes. Diclofenac sodium eye drops reduced
      concentrations of prostaglandin E2 and SPLI in tears. Analysis using HPLC
      indicated that five different substances contributed to SPLI in tears and that SP
      was broken down into several fragments, including SP(8-11), by enzymes present in
      tears. CONCLUSIONS: Substance P is a normal component of human tears. Levels of
      SPLI in tears might reflect the denervated status of the ocular surface.
      Substance P is catabolized by degradative enzymes in tears to maintain the ocular
      surface by exerting the trophic effects of SP while avoiding undesirable effects.

PMID- 14703708
TI  - Quantitative analysis of herpes simplex virus genome in tears from patients with
      herpetic keratitis.
AB  - PURPOSE: Herpetic keratitis is manifested in various corneal disorders, for
      example, dendritic keratitis, persistent epithelial defect, disciform keratitis,
      and endotheliitis. In this paper, we report on the quantity of herpes simplex
      virus (HSV) genome in tears from patients with various types of herpetic
      keratitis in an attempt to understand the role of HSV in these conditions.
      METHODS: We collected tear samples from both eyes of 56 consecutive patients with
      herpetic keratitis who visited Kinki University Hospital between June 2000 and
      May 2002. All patients had unilateral herpetic keratitis: epithelial keratitis in
      27 eyes; persistent epithelial defect in 6; active disciform stromal keratitis in
      14; silent stromal keratitis in 6; and endotheliitis in 3. We measured levels of
      HSV genome in these tear samples using a real-time polymerase chain reaction
      (PCR) method. RESULTS: In epithelial keratitis, HSV DNA was detected in all 27
      samples from affected eyes (6.4 +/- 4.4 x 10(5) copies/sample). In persistent
      epithelial defect, HSV DNA was detected in all 6 samples from affected eyes (8.5
      +/- 3.3 x 10(4) copies/sample). In active disciform stromal keratitis, HSV DNA
      was detected in 8 of the 14 affected eyes (1.4 +/- 1.1 x 10(5) copies/sample
      including zero values in negative samples). HSV DNA was not detected in samples
      from unaffected eyes or eyes affected by silent stromal keratitis or
      endotheliitis. CONCLUSION: Real-time PCR is a useful method for quantifying HSV
      DNA in tear samples from patients with herpetic keratitis. Using this method, we
      demonstrate that HSV reproduction occurs in persistent epithelial defect and
      disciform stromal keratitis.

PMID- 14703709
TI  - Role of resident corneal leukocytes and draining cervical lymph nodes in corneal
      allograft rejection.
AB  - We review recently published experimental evidence on corneal transplant
      immunology involving cornea and draining cervical lymph nodes (CLNs) in the
      mouse. In the cornea, major histocompatibility complex (MHC) class II- dendritic
      cells (DCs) are present in the corneal epithelium. These DCs can express MHC
      class II antigen in vivo and in vitro. In the corneal stroma, there are many
      leukocytes of monocyte or macrophage lineage. Normal cornea has been reported to
      contain a significant number of bone marrow-derived resident cells, which may be
      able to act as antigen-presenting cells. Allograft rejection does not occur if
      draining CLNs are removed before corneal transplantation, indicative of an
      essential role of CLNs in promoting corneal allorejection. Moreover, donor cornea
      derived DCs were detected in host draining CLNs in a mouse corneal
      transplantation model. These findings provide direct evidence that MHC class II-
      bone marrow-derived antigen-presenting leukocytes exist in the part of cornea
      used for transplantation and that direct allorecognition of antigen is, at least
      in part, relevant to the occurrence of corneal allograft rejection in which
      draining CLNs play a central role.

PMID- 14703710
TI  - Transplantation of cultured human corneal endothelial cells.
AB  - PURPOSE: To investigate the feasibility of corneal reconstruction utilizing
      cultured human corneal endothelial cells (HCECs). METHODS: We cultivated HCECs
      using culture dishes pre-coated with bovine corneal endothelial extracellular
      matrix. The effect of donor age on HCECs was investigated. We reconstructed
      corneas using cultured HCECs and human corneal stroma, then examined their
      functioning. The possibility of porcine corneal stroma as a carrier of cultured
      HCECs was investigated. RESULTS: The older the donor, the more frequently large
      senescent cells appeared in the passaged HCECs. The density of HCECs on the
      reconstructed cornea reached 2500 cells/mm2. The potential difference in the
      reconstructed and normal corneas was 0.30 mV and 0.40 mV, respectively; this
      indicates that the pump function of the reconstructed corneas is 75% of that of
      normal corneas. Porcine corneal stroma expressing little xenosugar antigen alpha
      gal epitope induced no superacute rejection but mild cellular rejection when
      transplanted into corneas of animals possessing natural antibody to alpha-gal
      epitope. CONCLUSIONS: To reconstruct corneas that are the same as, or superior
      to, normal corneas, innovation is necessary in the methods used for culturing and
      seeding HCECs. Porcine corneal stroma is promising as a carrier of HCECs instead
      of human corneal stroma, the supply of which is limited. The validity of porcine
      corneal stroma, acellularized to prevent retrovirus infection, should be
      evaluated.

PMID- 14703711
TI  - Ocular surface reconstruction using cultivated mucosal epithelial stem cells.
AB  - PURPOSE: To investigate the possibility of using cultivated oral epithelial cells
      in ocular surface reconstruction. METHODS: An ocular surface injury was created
      in adult albino rabbits by a lamellar keratectomy. Oral mucosal biopsy specimens
      taken from both adult albino rabbits and human volunteers were cultivated for 2-3
      weeks on a denuded amniotic membrane (AM) carrier. The cultivated epithelium was
      examined by histologic and immunohistochemical analysis. At 3-4 weeks after the
      ocular surface injury, the rabbit conjunctivalized corneal surfaces were
      surgically reconstructed by transplanting both the rabbit and human cultivated
      oral epithelial cells on the AM carrier. RESULTS: Both the rabbit and human
      cultivated oral epithelial sheets had 5 or 6 layers of stratified, well
      differentiated cells. Histologic examination revealed that the cultivated
      epithelial cells were similar in appearance to those of in vivo normal corneal
      epithelium. Immunohistochemistry confirmed the presence of the keratin pair 4 and
      13 and keratin 3 in the cultivated oral epithelial cells. Corneas that were
      grafted with rabbit and human cultivated oral epithelial cells on an AM carrier
      were clear and were epithelialized 10 and 2 days after surgery, respectively.
      CONCLUSIONS: We have generated confluent cultures of both rabbit and human oral
      epithelial cells on AM expanded ex vivo from biopsy-derived oral mucosal tissues.
      We have successfully carried out xeno- and autologous transplantation of these
      cultivated oral epithelial cells onto the ocular surfaces of keratectomized
      rabbit eyes. We believe that xeno- and autologous transplantation of cultivated
      oral epithelium is a feasible method for ocular surface reconstruction.

PMID- 14703712
TI  - Collagen-poly(N-isopropylacrylamide)-based membranes for corneal stroma
      scaffolds.
AB  - PURPOSE: To investigate the feasibility of using the biocompatibility of collagen
      based blended biomaterials as cell-delivery systems in ocular surface
      reconstruction in vivo. METHODS: Collagen-based composites that were blended with
      synthetic acrylamide-based polymers [poly(N-isopropylacrylamide), pNIPAAm] were
      transplanted into corneal pockets of white rabbits, with a 3-mm epithelial
      window. Epithelial cells were allowed to migrate onto the polymer. Transplanted
      eyes were examined daily for up to 30 days, after which animals were killed for
      histologic examination. Immunohistochemistry was performed for vimentin, alpha
      smooth muscle actin (alpha-SMA), CD4, and CD8. Gold-chloride staining was
      performed to observe neuronal regrowth. Human amniotic membranes (AMs) and sham
      operated corneas served as controls. All animals received topical antibiotics
      (levofloxacin) without the use of steroids or other immunosuppressive agents.
      RESULTS: The pNIPAAm polymer allowed smooth epithelialization of the cornea,
      which was similar to the epithelialization observed in sham controls and AM
      transplanted eyes. Histology revealed that epithelium overlying the polymer was
      bundled into several layers, without the orientation observed with AM and sham
      controls. The polymer gradually thinned and was gradually replaced by host
      tissue. Vimentin- and alpha-SMA-positive cells were found in stromal pockets up
      to 1 month following polymer transplantation. These cells were responsible for
      slight subepithelial haze near the wound edge. CD4- and CD8-positive lymphocytes
      were also observed in the vicinity of the polymer. Gold-chloride staining showed
      nerve regrowth in the wound edge after 1 month and subepithelial branches after 3
      months. CONCLUSION: Collagen-pNIPAAm blended polymers may be effective as
      biomaterials to be used in the early stages of lamellar stromal replacement

PMID- 14703713
TI  - Sequential methods and group sequential designs for comparative clinical trials.
AB  - Comparative clinical trials are performed to assess whether a new treatment has
      superior efficacy than a placebo or a standard treatment (one-sided formulation)
      or whether two active treatments have different efficacies (two-sided
      formulation) in a given population. The reference approach is the single-stage
      design and the statistical test is performed after inclusion and evaluation of a
      predetermined sample size. In practice, the single-stage design is sometimes
      difficult to implement because of ethical concerns and/or economic reasons. Thus,
      specific early termination procedures have been developed to allow repeated
      statistical analyses to be performed on accumulating data and stop the trial as
      soon as the information is sufficient to conclude. Two main different approaches
      can be used. The first one is derived from strictly sequential methods and
      includes the sequential probability ratio test and the triangular test. The
      second one is derived from group sequential designs and includes Peto, Pocock,
      and O'Brien and Fleming methods, alpha and beta spending functions, and one
      parameter boundaries. We review all these methods and describe the bases on which
      they rely as well as their statistical properties. We also compare these methods
      and comment on their advantages and drawbacks. We present software packages which
      are available for the planning, monitoring and analysis of comparative clinical
      trials with these methods and discuss the practical problems encountered when
      using them. The latest versions of all these methods can offer substantial sample
      size reductions when compared with the single-stage design not only in the case
      of clear efficacy but also in the case of complete lack of efficacy of the new
      treatment. The software packages make their use quite simple. However, it has to
      be stressed that using these methods requires efficient logistics with real-time
      data monitoring and, apart from survival studies or long-term clinical trials
      with censored endpoints, is most appropriate when the endpoint is obtained
      quickly when compared with the recruitment rate.

PMID- 14703714
TI  - Metabolic drug interactions with new psychotropic agents.
AB  - New psychotropic drugs introduced in clinical practice in recent years include
      new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and
      'third generation' antidepressants, and atypical antipsychotics, i.e. clozapine,
      risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents
      are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are
      therefore susceptible to metabolically based drug interactions with other
      psychotropic medications or with compounds used for the treatment of concomitant
      somatic illnesses. New antidepressants differ in their potential for metabolic
      drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6,
      fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent
      inhibitor of CYP3A4. These antidepressants may be involved in clinically
      significant interactions when coadministered with substrates of these isoforms,
      especially those with a narrow therapeutic index. Other new antidepressants
      including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are
      weak in vitro inhibitors of the different CYP isoforms and appear to have less
      propensity for important metabolic interactions. The new atypical antipsychotics
      do not affect significantly the activity of CYP isoenzymes and are not expected
      to impair the elimination of other medications. Conversely, coadministration of
      inhibitors or inducers of the CYP isoenzymes involved in metabolism of the
      various antipsychotic compounds may alter their plasma concentrations, possibly
      leading to clinically significant effects. The potential for metabolically based
      drug interactions of any new psychotropic agent may be anticipated on the basis
      of knowledge about the CYP enzymes responsible for its metabolism and about its
      effect on the activity of these enzymes. This information is essential for
      rational prescribing and may guide selection of an appropriate compound which is
      less likely to interact with already taken medication(s).

PMID- 14703715
TI  - Structure and pharmacology of swelling-sensitive chloride channels, I(Cl,swell).
AB  - Since several years, the interest for chloride channels and more particularly for
      the enigmatic swelling-activated chloride channel (I(Cl,swell)) is increasing.
      Despite its well-characterized electrophysiological properties, the I(Cl,swell)
      structure and pharmacology are not totally elucidated. These channels are
      involved in a variety of cell functions, such as cardiac rhythm, cell
      proliferation and differentiation, cell volume regulation and cell death through
      apoptosis. This review will consider different aspects regarding structure,
      electrophysiological properties, pharmacology, modulation and functions of these
      swelling-activated chloride channels.

PMID- 14703716
TI  - Inhibitors of swelling-activated chloride channels increase infarct size and
      apoptosis in rabbit myocardium.
AB  - Apoptosis is a significant contributor to myocardial cell death during ischemia
      reperfusion and swelling-activated chloride channels (I(Cl,swell)) contribute to
      apoptosis. However, the relationship between I(Cl,swell) ischemia-reperfusion and
      apoptosis remains unknown. To further investigate this, New Zealand rabbits
      underwent a 20-min coronary artery occlusion (CAO) followed by 72 h of coronary
      artery reperfusion (CAR). Two I(Cl,swell) blockers, 5-nitro-2-[3
      phenylpropylamino]benzoic acid (NPPB) and indanyloxyacetic acid 94 (IAA-94) (both
      1 mg/kg), were administered prior to CAO and throughout the 72 h CAR. Infarct
      size (IS) was increased with NPPB and IAA-94 compared with control (vehicle)
      rabbits (51 +/- 2% and 48 +/- 3% and vs. 35 +/- 2%, respectively, P < 0.05).
      Similar results were found when NPPB was administered only during the reperfusion
      period. The percentage of TUNEL-positive nuclei in the border zone of the infarct
      was increased with NPPB compared with control (37 +/- 2% vs. 25 +/- 31%, P <
      0.05) as well as the number of cytoplasmic histone-associated DNA fragments (0.45
      +/- 0.06 vs. 0.33 +/- 0.04 absorbance units, P < 0.05). These findings support
      the concept that I(Cl,swell) channels play an important role in the determination
      of myocardial infarct size and apoptosis during ischemia-reperfusion.

PMID- 14703717
TI  - Role of nitric oxide in the CBF autoregulation during acute stage after
      subarachnoid haemorrhage in rat pial artery.
AB  - The present study was aimed to identify whether endogenously produced nitric
      oxide (NO) plays a role in preservation of cerebral blood flow (CBF)
      autoregulation in rat pial artery during the acute stage after subarachnoid
      haemorrhage (SAH). During the acute stage after SAH, the lower limit of CBF
      autoregulation significantly shifted to the higher arterial blood pressure in
      association with suppressed vasodilatation in response to acute hypotension,
      which was accompanied by significantly increased expression of endothelial nitric
      oxide synthase mRNA and increased production of superoxide anion in cerebral
      vessels. SAH-induced increase in superoxide production was further enhanced under
      pretreatment with N-nitro-L-arginine methyl ester in the cerebral vessels.
      Following additional administration of L-arginine (100 mg/kg, i.p.), the
      haemodynamic alterations were significantly restored in association with
      significantly reduced superoxide level in the cerebral vessels. In line with
      these findings, rats that received polyethylene glycol superoxide dismutase and
      catalase or Mn(III) tetrakis (4-benzoic acid) porphyrin chloride showed recovery
      of impaired autoregulatory vasodilation in response to acute hypotension. Thus,
      it is suggested that NO endogenously produced is importantly implicated in the
      preservation of CBF autoregulation during the acute stage after SAH via its
      capability to scavenge superoxide anion.

PMID- 14703718
TI  - A QSAR analysis to explain the analgesic properties of Aconitum alkaloids.
AB  - Aconitum roots are traditionally prescribed for the management of different types
      of painful affections in Asiatic countries. A quantitative structure-activity
      relationship (QSAR) analysis was performed to study the effect of chemical
      substitutes in the analgesic potency of alkaloids available in Chinese Aconitum
      roots. Using the CAChe program package for biomolecules, molecular modelling was
      performed in 12 alkaloids previously tested in a model of acetic acid-induced
      writhing in rats. The ED50 (micromol/kg) was used as the activity parameter.
      Structural parameters were compared between alkaloids with an aroyl/aroyloxy
      group at R14 and alkaloids with the aroyloxy group at R4. Single linear
      regression analyses were performed in order to find the parameters explaining
      activity. Alkaloids with an aroyl/aroyloxy group at R14 exhibited the highest
      potency (significantly less ED50). The stability parameters were different
      between groups, e.g. total energy was -8.0 +/- 0.4 in the potent analgesic
      alkaloids and -6.7 +/- 0.3 in the weak analgesic alkaloids (P = 0.001). The
      reactivity index of C2', C3' and C5' of the aromatic ring was also different
      between groups, e.g. the reactivity index of C5' was 40.8 +/- 0.6 in potent
      analgesic alkaloids and 48.1 +/- 0.6 in weaker analgesic alkaloids (P < 0.001).
      Several structural parameters explained analgesic activity of alkaloids, being
      the reactivity index of C5' on the aromatic group the most important factor (r =
      0.89; P < 0.001).

PMID- 14703719
TI  - Neuroprotection assessment by topographic electroencephalographic analysis:
      effects of a sodium channel blocker to reduce polymorphic delta activity
      following ischaemic brain injury in rats.
AB  - The spatiotemporal electroencephalogram (EEG) pathology associated with brain
      injury was studied using high-resolution, 10-electrode cortical EEG mapping in a
      rat model of middle cerebral artery occlusion (MCAo). Using this model we
      evaluated the ability of the novel sodium channel blocker and neuroprotective
      agent RS100642 to resolve injury-induced EEG abnormalities as a measure of
      neurophysiological recovery from brain injury. The middle cerebral artery (MCA)
      was occluded for 1 h during which a dramatic loss of EEG power was measured over
      the injured cortex with near complete recovery upon reperfusion of blood to the
      MCA region in all rats. The resultant progression of the MCAo/reperfusion injury
      (6-72 h) included the appearance of diffuse polymorphic delta activity (PDA), as
      visually indicated by the presence of high-amplitude slow-waves recorded from
      both brain hemispheres. PDA was associated with large increases in EEG power,
      particularly evident in outer 'peri-infarct' regions of the ipsilateral parietal
      cortex as visualized using topographic EEG mapping. Post-injury treatment with
      RS100642 (1.0 mg/kg, i.v.) significantly reduced the PDA activity and attenuated
      the increase in EEG power throughout the course of the injury. These effects were
      associated with a reduction in brain infarct volume and improved neurological
      function. These methods of EEG analysis may be helpful tools to evaluate the
      physiological recovery of the brain from injury in humans following treatment
      with an experimental neuroprotective compound.

PMID- 14703720
TI  - The preventive effect of captopril or enalapril on reperfusion injury of the
      kidney of rats is independent of angiotensin II AT1 receptors.
AB  - Occlusion of the artery of organs results in ischaemia. The opening of occluded
      artery results in tissue lesion identified as reperfusion injury (RI). Renin
      angiotensin system seems to be involved in the RI. In this study we assessed the
      effects of different doses of two inhibitors of angiotensin converting enzyme
      (captopril or enalapril) and an angiotensin receptor type 1 (AT1) receptor
      blocker (losartan) in the RI of the kidney of rats. Female rats of 200-250 g were
      anaesthetized and used for RI studies. Different doses of captopril (5, 20 and 80
      mg/kg), enalapril (1, 4 and 16 mg/kg) and/or losartan (5, 10 and 20 mg/kg) were
      used (s.c.) 120 min prior to the initiation of RI. Kidneys were removed and
      checked histologically for the presence and the grading of ischaemic injury.
      Appropriate controls were used as well, RI produced lesions comparable with that
      of ischaemia. Different doses of captopril or enalapril prevented these lesions.
      This is suggestive of the involvement of renin-angiotensin system in the RI.
      Different doses of losartan failed to prevent RI lesions which suggest that the
      effect of captopril or enalapril are not mediated through the AT1 receptors.
      Further studies on the involvement of AT2 receptor or other independent
      mechanisms are suggested.

PMID- 14703721
TI  - Activation of DNA biosynthesis in human hepatoblastoma HEPG2 cells by the nitric
      oxide donor, sodium nitroprusside.
AB  - The role of nitric oxide (NO) in carcinogenesis is controversial as it has been
      shown to both stimulate and inhibit tumour growth. Also, there are contradictory
      opinions regarding the effects of NO on the proliferation of normal and tumour
      cells. The aim of our study was to use an in vitro model to determine the
      influence of exogenous NO donors on DNA biosynthesis by measuring [3H] thymidine
      incorporation in human hepatoblastoma cells (HepG2). The studies were conducted
      with the following NO precursors: sodium nitroprusside (SNP), S
      nitrosoglutathione, and nitroglycerine (NTG). Out of all three NO donors, SNP
      increased NO levels and strongly stimulated DNA biosynthesis. A SNP concentration
      of 150 microM induced optimal NO levels necessary for the activation of DNA
      biosynthesis. Lower levels of DNA biosynthesis (118% increase over the control)
      were observed in the presence of NTG, whereas S-nitrosoglutathione had no effect.
      Antioxidants such as thiol-containing drugs, N-acetylcysteine and tocopherol,
      proved to be the most efficient co-activators of SNP-induced DNA synthesis. On
      the other hand, supplementing the SNP-containing medium with compounds that
      induce oxidative stress and lower the level of -SH groups such as hydrogen
      peroxide, doxorubicin, and N-ethylmaleimide, led to the inhibition of DNA
      synthesis. Therefore, our results firmly confirm the hypothesis that biological
      effects of exogenous NO donors depends on the redox status of the cell.

PMID- 14703722
TI  - Inhibition of L-arginine transport by reactive oxygen species in rat anococcygeus
      muscle.
AB  - The effect of L-arginine on nitrergic transmission and its alteration with
      reactive oxygen species (ROS) were investigated. L-arginine potentiated the
      relaxation response induced by electrical field stimulation in rat anococygeus
      muscle. This effect was inhibited by L-lysine, a cationic amino acid using y+ L
      and y+ transport systems in a similar way with L-arginine. The neutral amino acid
      L-leucine, which uses only y+ L system as a transport mechanism, inhibited this
      potentiation at only low frequency stimulation. Electrolysis of the physiological
      solution did not change the responses to electrical field stimulation, but
      inhibited the potentiation elicited by L-arginine that was prevented in the
      presence of mannitol and N-acetyl-L-cysteine. In conclusion, L-arginine is
      transported via y+ system predominantly to potentiate the relaxation response to
      nitrergic nerve stimulation in rat anococcygeus muscle. ROS, primarily hydroxyl
      radicals inhibited L-arginine-induced potentiation probably by interacting with
      the y+ amino acid transport system.

PMID- 14703723
TI  - Assessing immunotoxicity: guidelines.
AB  - Over the last couple of years the assessment of immunotoxic potential of human
      pharmaceuticals has drawn considerable attention worldwide. Regulatory agencies
      entrusted with the registration of pharmaceuticals (or other compounds) found an
      increased need for guidance on this issue. This has resulted in the release of
      guidance documents on immunotoxicity in Europe, USA and Japan in close
      succession. In Europe the CPMP has released their immunotoxicity guidance
      documents that are now in force. The FDA and the Japanese Authorities are in the
      process of doing so, and will shortly enforce them. Immune suppression and
      stimulation, hypersensitivity, photosensitivity, drug-induced autoimmunity and
      developmental immunotoxicity are the focus of regulatory testing. This review
      discusses these kinds of immunotoxicity and their clinical implications. The
      three regional guidelines and screening tools for detection are discussed.
      Additionally, the scientific background on which these guidelines are based is
      briefly highlighted.

PMID- 14703724
TI  - Cough after inhalation of corticosteroids delivered from spacer devices in
      children with asthma.
AB  - Children using a spacer device rather than another device for delivering inhaled
      corticosteroids (ICS) has been identified as a risk factor for cough immediately
      after inhalation. The aim of this study was to point out the different factors
      influencing the occurrence of such lateral side-effects. We studied this local
      side-effect in 402 asthmatic children (55.6 +/- 34.9 months; 65.6% boys) treated
      for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n =
      47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose
      inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used
      with face mask (90.7%). A total of 219 patients (54.5%), treated with either high
      doses of ICS or ICS and long-acting beta2-agonist, were considered as having
      severe asthma. Cough was reported after each inhalation of corticosteroids in 216
      patients (53.7%). Among them, about 30% also complained of cough with beta2
      agonists. Despite different propellants and dispersants, all corticosteroids
      induced cough similarly. Cough was not linked with asthma severity, but was
      significantly related to therapy duration and use of long-acting beta2-agonist.
      Type and volume of the spacer device, use of a face mask or mouthpiece were not
      influencing factors. Cough after inhalation of corticosteroids delivered from
      spacer devices is a frequent local side-effect in children with asthma. This side
      effect can greatly alter compliance. A practitioner must be sought at each visit.

PMID- 14703725
TI  - Increased adrenergic contractility and decreased mRNA expression of NOS III in
      aging rat urinary bladders.
AB  - Our objective was to study age-related changes in adrenergic contractility and
      gene expression profile in the rat urinary bladder. Young (3-month old), adult
      (10-month old) and senescent (30-month old) male WAG/Rij rats were used. Gene
      expression profile in the rat urinary bladder was defined using Atlas microarray
      technology. In vitro contractile responses induced by KCl, phenylephrine (PHE)
      and norepinephrine (NE) were compared in isolated urinary bladders dissected from
      young, adult and senescent rats. Among a total of 1176 genes present on the
      arrays, 15 genes showed an increase in expression and 10 genes a decrease with
      age. Four genes related to nerve growth factor were upregulated whereas NOS type
      III was downregulated in aging rats. Intrinsic contractility of isolated rat
      urinary bladders was not changed between adult and aging rats as judged by the
      response curves to KCl. In contrast, an age-related increase in the maximal
      contractile responses to NE, but not PHE, was noticed (13 +/- 1, 48 +/- 2% and 59
      +/- 2% at 3, 10 and 30 months, respectively). The alpha1D-adrenoceptor antagonist
      BMY7378 antagonized NE-induced contractions with low potency in both groups
      suggesting the involvement of the alpha1A-adrenoceptor subtype. This was
      confirmed by microarray, which demonstrated mRNA expression for the alpha1A
      adrenoceptor subtype only. These results suggest that aging of the urinary
      bladder is associated with an increase in the maximal contractile response to NE
      which could be due to NO shortage resulting from downregulation of urothelial NOS
      III.

PMID- 14703726
TI  - Free and peptide-bound DOPA can inhibit initiation of low density lipoprotein
      oxidation.
AB  - Hydroxyl radicals have been shown to convert free tyrosine to 3,4-dihydroxyphenyl
      alanine (DOPA) which has reducing properties. During protein or peptide oxidation
      such reducing species are also formed from tyrosine residues. Free DOPA or
      peptide-bound DOPA (PB-DOPA) is able to promote radical-generating events,
      facilitating the damage of biomolecules such as nucleic acids. Radical induced
      lipid oxidation in low density lipoprotein (LDL) transforms the lipoprotein into
      an atherogenic particle. As PB-DOPA has been found in atherosclerotic plaques, we
      tested the ability of free and PB-DOPA to influence LDL oxidation. Free DOPA, in
      contrast to tyrosine had strong inhibitory action on both, the copper-ion
      initiated and metal ion independent (AAPH-induced) lipid oxidation. Free DOPA
      also inhibited LDL oxidation induced by the copper transport protein
      ceruloplasmin. To test if PB-DOPA was also able to inhibit LDL oxidation, DOPA
      residues were generated enzymatically in the model peptides insulin and tyr-tyr
      tyr, respectively. PB-DOPA formation substantially increased the ability of both
      molecules to inhibit LDL oxidation by copper or AAPH. We hypothesize that DOPA
      peptides and -proteins may have the potential to act as efficacious antioxidants
      in the atherosclerotic plaque.

PMID- 14703727
TI  - 1-Methyl-3-nitropyridine: an efficient oxidant of NADH in non-enzymatic and
      enzyme-mediated processes.
AB  - It is shown that NADH can be effectively oxidized by 1-methyl-3-nitropyridine in
      non-enzymatic and enzyme-mediated processes. Mechanistic issues of these
      reactions are discussed. These processes seem to contribute to the observed
      cytotoxicity of 1-methyl-3-nitropyridine. A key role of 1-methyl-3-nitropyridinyl
      radical formed in the enzyme-mediated processes is emphasized.

PMID- 14703728
TI  - The ozone tolerance: I) Enhancement of antioxidant enzymes is ozone dose
      dependent in Jurkat cells.
AB  - We have begun to examine the biological and toxic effects of ozone on Jurkat T
      cells incubated thereafter for 24, 48 and 72 h. Tissue culture medium was
      strengthened by adding 20% fetal calf serum with an albumin content of about 6
      mg/ml. Ozonization was performed by exposing for 10 min a volume of cell
      suspension (4 x 10(5)/ml) to an equal volume of a gas mixture composed of oxygen
      ozone with precise ozone concentrations ranging from 1.5 up to 72 microg/ml (31.5
      1512 microM). The proliferation index declined progressively and was ozone dose
      dependent. The response of enzymatic activities varied depending upon the enzyme
      and ozone concentrations: glucose-6-phosphate dehydrogenase begins to increase at
      an ozone dose of 6 microg/ml (126 microM), reached a peak at 12 microg/ml (252
      microM) and rapidly declined thereafter. On the other hand activities of
      superoxide dismutase, glutathione peroxidase and glutathione reductase increased
      progressively from the ozone concentration of 12 microg/ml. Thus, as we have
      observed in blood, the biological response is linked to the ozone dose that must
      reach a threshold to be effective.

PMID- 14703729
TI  - Diabetes-induced activation of nuclear transcriptional factor in the retina, and
      its inhibition by antioxidants.
AB  - Oxidative stress is increased in the retina in diabetes, and long-term
      administration of antioxidants inhibits the development of retinopathy in
      diabetic rats. The purpose of this study is to determine how diabetes affects the
      activation of a redox-sensitive nuclear transcriptional factor in the retina, NF
      kappaB, and its inhibition by antioxidants. Alloxan diabetic rats were assigned
      to receive standard diet or the diet supplemented with multiple antioxidants,
      including ascorbic acid, Trolox, dl alpha-tocopherol acetate, N-acetyl cysteine,
      beta-carotene, and selenium for up to 14 months. NF-kappaB activation, oxidative
      stress and nitric oxides were measured in the retina at 2, 8 and 14 months of
      diabetes. Retinal NF-kappaB was activated by about 60% at two months after
      induction of diabetes, remained activated for up to 14 months of diabetes, and
      the duration of diabetes had no effect on the intensity of NF-kappaB activation.
      Similarly, oxidative stress and nitric oxides were elevated by over 50% in the
      retina of rats diabetic for 14 months, and nitrotyrosine levels were elevated by
      over two folds. Administration of the antioxidants to the rats for the entire
      duration of diabetes inhibited activation of NF-kappaB and elevations in
      oxidative stress, nitric oxides and nitrotyrosine formation without ameliorating
      the severity of hyperglycemia. These in vivo results were confirmed by in vitro
      studies showing that high glucose activates NF-kappaB and elevates NO and lipid
      peroxides in both retinal endothelial cells and pericytes that can be inhibited
      by antioxidants. Thus, the results suggest that the activation of retinal NF-KB
      in diabetes is an early event in the development of retinopathy, and it remains
      active when the retinal capillary cell death is accelerating, and histopathology
      is developing. Beneficial effects of antioxidants on the development of diabetic
      retinopathy might involve inhibition of NF-kappaB activation and its downstream
      pathways in the retina.

PMID- 14703730
TI  - The influence of oxidative bursts of phagocytes on red blood cell oxidation in
      anemic cattle infected with Theileria sergenti.
AB  - The primary clinical symptom of Japanese bovine theileriosis, caused by the
      intraerythrocytic protozoan Theileria sergenti, is anemia, but the underlying
      mechanism of this anemia remains unknown. To elucidate the pathogenesis of anemia
      developing in bovine theileriosis, we investigated the relationship between
      oxidative bursts of peripheral blood phagocytes (neutrophils and monocytes) and
      the oxidation of red blood cells (RBC) to the development of anemia in cattle
      experimentally infected with T. sergenti. The levels of methemoglobin (MetHb) and
      malondialdehyde (MDA), as a parameter of intracellular and membrane oxidative
      damage in RBC and of production of hydrogen peroxide (H2O2) in phagocytes, were
      low before the onset of anemia; these parameters began to increase remarkably
      with decreasing packed cell volume and increasing parasitemia during the course
      of the anemia, which returned to initial levels during convalescence from anemia.
      A positive correlation between H2O2 production of phagocytes and each of the
      oxidative indices of MetHb and MDA was also noted during the onset of anemia. The
      levels of antioxidants, namely reduced glutathione and glucose-6-phosphate
      dehydrogenase, in RBC also decreased during the progression of anemia. These
      results suggest that oxidative damage of RBC has a close relationship with the
      onset of anemia in bovine theileriosis, and that oxidative bursts of phagocytes
      may play a part in the pathogenesis of anemia in infected cattle.

PMID- 14703731
TI  - Amifostine has antiangiogenic properties in vitro by changing the redox status of
      human endothelial cells.
AB  - Amifostine is a broad-spectrum cytoprotective agent, selective for normal
      tissues. It is a pro-drug metabolised to the free thiol WR-1065 that may act as a
      scavenger of free radicals, generated in tissues exposed to chemotherapeutic
      agents or radiation. WR-1065 can be further oxidized to its symmetric disulfide
      WR-33278 or degraded to hydrogen peroxide (H2O2). Both WR-1065 and WR-33278
      resemble endogenous polyamines. Although amifostine is used in some cases in the
      clinic, there are only few studies concerning its actions at the cellular level.
      We have previously shown that amifostine inhibits angiogenesis in vivo, affecting
      the expression of several angiogenic genes. In the present work, we studied the
      effect of amifostine on human umbilical vein endothelial cell (HUVEC) functions
      in vitro, in order to further clarify its mechanism(s) of action. Amifostine
      increased HUVEC proliferation, an effect that was reversed by the intracellular
      H2O2 scavenger sodium pyruvate, agents that increase intracellular cAMP levels
      and L-valine. On the other hand, amifostine decreased HUVEC migration, an effect
      that was reversed by L-valine or L-arginine but not sodium pyrouvate. The
      decrease in migration was in line with decreased tube formation on matrigel and
      decreased amounts of metalloproteinase-2 released into the culture medium of
      HUVEC. Finally, amifostine reduced tyrosine nitration of the cytoskeletal
      proteins actin and alpha-tubulin in a time dependent manner. This last action
      could be due to the reduced production of nitric oxide (NO) or to other not yet
      identified mechanisms. Collectively, our results suggest that amifostine acts on
      endothelial cells through pathways that affect the redox status of the cells,
      either by producing H2O2 or by modulating NO production.

PMID- 14703732
TI  - Deleterious activation of poly(ADP-ribose)polymerase-1 in brain after in vivo
      oxidative stress.
AB  - Oxidative stress has been shown to be implicated in the pathogenesis of central
      nervous system injuries such as cerebral ischemia and trauma, and chronic
      neurodegenerative diseases. In vitro studies show that oxidative stress,
      particularly peroxynitrite, could trigger DNA strand breaks, which lead to the
      activation of repairing enzymes including Poly(ADP-ribose) Polymerase-1 (PARP-1).
      As excessive activation of this enzyme induces cell death, we examined whether
      such a cascade also occurs in vivo in a model of oxidative stress in rat brain.
      For this purpose, the mitochondrial toxin malonate, which promotes free radical
      production, was infused into the left striatum of rats. Immunohistochemistry
      showed that 3-nitrotyrosine, an indicator of nitrosative stress, and poly(ADP
      ribose), a marker of poly(ADP-ribose)polymerase-1 activation, were present as
      early as 1 h after malonate, and that they persisted for 24 h. The PARP
      inhibitor, 3-aminobenzamide, significantly reduced the lesion and inhibited PARP
      1 activation induced by malonate. These results demonstrate that oxidative stress
      induced in vivo in the central nervous system leads to the activation of poly(ADP
      ribose)polymerase-1, which contributes to neuronal cell death.

PMID- 14703733
TI  - Hydrogen peroxide in urine as a potential biomarker of whole body oxidative
      stress.
AB  - The level of hydrogen peroxide (H2O2) in urine has been suggested as a potential
      biomarker of whole body oxidative stress, but issues of stability,
      reproducibility and biological variation have not been investigated to date. In
      this study, we used a refined protocol, which demonstrated improved sensitivity
      and precision, to determine the stability of H2O2 in urine, and to measure its
      concentration in apparently healthy subjects. We also investigated intra
      individual variation within and between days. Results showed that H2O2 in urine
      is stable for up to 48 h at 4 degrees C, however, storage of urine at room
      temperature was associated with up to 50% increase in H2O2 concentration over a
      few hours. Total H2O2 in freshly voided urine from 55 healthy, fasting subjects
      ranged from 0.84 to 5.71 microM, or 90-1164 micromol H2O2/mol creatinine. Intra
      individual variation was wide. Even when concentration corrected and collected at
      the same time of day, 2- to 3-fold variation was seen over 4 consecutive days,
      and over the course of a single day the creatinine-corrected H2O2 also varied
      significantly. We suggest that this large biological variation limits the
      usefulness of urine H2O2 as a biomarker of oxidative stress, the exception being
      when the effects of disease, therapy or diet induce very large changes in its
      concentration.

PMID- 14703734
TI  - Effects of the phenolic contents of Mauritian endemic plant extracts on promoter
      activities of antioxidant enzymes.
AB  - Oxidative stress has been associated with a variety of pathologic conditions in
      humans. Increasing the transcriptional activities of antioxidant enzymes might be
      a strategy to prevent oxidative stress-associated diseases such as
      atherosclerosis and cancer. In the present paper, we studied the effects of
      extracts from 12 Mauritian endemic plants on the promoter activities of
      antioxidant enzymes; Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide
      dismutase (Mn-SOD), catalase, and glutathione dismutase (GPx). The levels of
      total phenolic compounds, total flavonoids, and proanthocyanidins were measured.
      Four luciferase expression vectors (pGL3-Basic) with promoter region of each
      enzyme were constructed, transfected to COS7 cells followed by an exposure to
      each extract (25 microg/ml, 24h, non-toxic dose). Thereafter, luciferase
      activities were evaluated in comparison with a control luciferase vector with a
      herpes simplex virus thymidine kinase promoter. Mauritian endemic plants
      contained high amounts of total phenols, flavonoids and proanthocyanidins. Total
      phenols and flavonoids were proportionally associated with Cu,Zn-SOD promoter
      activity, whereas they were inversely correlated with catalase promoter activity.
      These results suggest that the chemopreventive potentials of the extracts might
      reside in their abilities to modulate the expression of the antioxidant enzyme
      genes.

PMID- 14703735
TI  - gamma-Tocopherol biokinetics and transformation in humans.
AB  - BACKGROUND: The uptake and biotransformation of gamma-tocopherol (gamma-T) in
      humans is largely unknown. Using a stable isotope method we investigated these
      aspects of gamma-T biology in healthy volunteers and their response to gamma-T
      supplementation. METHODS: A single bolus of 100 mg of deuterium labeled gamma-T
      acetate (d(2)-gamma-TAC, 94% isotopic purity) was administered with a standard
      meal to 21 healthy subjects. Blood and urine (first morning void) were collected
      at baseline and a range of time points between 6 and 240 h post-supplemetation.
      The concentrations of d(2) and d(0)-gamma-T in plasma and its major metabolite
      2,7,8-trimethyl-2-(b-carboxyethyl)-6-hydroxychroman (-gamma-CEHC) in plasma and
      urine were measured by GC-MS. In two subjects, the total urine volume was
      collected for 72 h post-supplementation. The effects of gamma-T supplementation
      on alpha-T concentrations in plasma and alpha-T and gamma-T metabolite formation
      were also assessed by HPLC or GC-MS analysis. RESULTS: At baseline, mean plasma
      alpha-T concentration was approximately 15 times higher than gamma-T (28.3 vs.
      1.9 micromol/l). In contrast, plasma gamma-CEHC concentration (0.191 micromol/l)
      was 12 fold greater than alpha-CEHC (0.016 micromol/l) while in urine it was 3.5
      fold lower (0.82 and 2.87 micromol, respectively) suggesting that the clearance
      of alpha-CEHC from plasma was more than 40 times that of gamma-CEHC. After d(2)
      gamma-TAC administration, the d(2) forms of gamma-T and gamma-CEHC in plasma and
      urine increased, but with marked inter-individual variability, while the d(0)
      species were hardly affected. Mean total concentrations of gamma-T and gamma-CEHC
      in plasma and urine peaked, respectively, between 0-9, 6-12 and 9-24 h post
      supplementation with increases over baseline levels of 6-14 fold. All these
      parameters returned to baseline by 72 h. Following challenge, the total urinary
      excretion of d(2)-gamma-T equivalents was approximately 7 mg. Baseline levels of
      gamma-T correlated positively with the post-supplementation rise of (d(0) + d(2))
      - gamma - T and gamma-CEHC levels in plasma, but correlated negatively with
      urinary levels of (d(0) + d(2))-gamma-CEHC. Supplementation with 100 mg gamma-TAC
      had minimal influence on plasma concentrations of alpha-T and alpha-T-related
      metabolite formation and excretion. CONCLUSIONS: Ingestion of 100mg of gamma-TAC
      transiently increases plasma concentrations of gamma-T as it undergoes sustained
      catabolism to CEHC without markedly influencing the pre-existing plasma pool of
      gamma-T nor the concentration and metabolism of alpha-T. These pathways appear
      tightly regulated, most probably to keep high steady-state blood ratios alpha-T
      to gamma-T and gamma-CEHC to alpha-CEHC.

PMID- 14703736
TI  - Oral alpha-tocopherol supplementation inhibits lipid oxidation in established
      human atherosclerotic lesions.
AB  - BACKGROUND: Much experimental evidence suggests that lipid oxidation is important
      in atherogenesis and in epidemiological studies dietary antioxidants appear
      protective against cardiovascular events. However, most large clinical trials
      failed to demonstrate benefit of oral antioxidant vitamin supplementation in high
      risk subjects. This paradox questions whether ingestion of antioxidant vitamins
      significantly affects lipid oxidation within established atherosclerotic lesions.
      METHODS AND RESULTS: This placebo-controlled, double blind study of 104 carotid
      endarterectomy patients determined the effects of short-term alpha-tocopherol
      supplementation (500 IU/day) on lipid oxidation in plasma and advanced
      atherosclerotic lesions. In the 53 patients who received alpha-tocopherol there
      was a significant increase in plasma alpha-tocopherol concentrations (from 32.66
      +/- 13.11 at baseline to 38.31 +/- 13.87 (mean +/- SD) micromol/l, p < 0.01), a
      40% increase (compared with placebo patients) in circulating LDL-associated alpha
      tocopherol (p < 0.0001), and their LDL was less susceptible to ex vivo oxidation
      than that of the placebo group (lag phase 115.3 +/- 28.2 and 104.4 +/- 15.7 min
      respectively, p < 0.02). Although the mean cholesterol-standardised alpha
      tocopherol concentration within lesions did not increase, alpha-tocopherol
      concentrations in lesions correlated significantly with those in plasma,
      suggesting that plasma alpha-tocopherol levels can influence lesion levels. There
      was a significant inverse correlation in lesions between cholesterol-standardised
      levels of alpha-tocopherol and 7beta-hydroxycholesterol, a free radical oxidation
      product of cholesterol. CONCLUSIONS: These results suggest that within plasma and
      lesions alpha-tocopherol can act as an antioxidant. They may also explain why
      studies using < 500 IU alpha-tocopherol/day failed to demonstrate benefit of
      antioxidant therapy. Better understanding of the pharmacodynamics of oral
      antioxidants is required to guide future clinical trials.

PMID- 14703737
TI  - Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin
      a bioflavonoid.
AB  - Cognitive dysfunction, one of the most striking age-related impairments seen in
      human beings, has been correlated to the vulnerability of the brain to increased
      oxidative stress during aging process. Quercetin is a bioflavonoid with strong
      antioxidant properties. Experiments were performed to study the possible effects
      of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice
      (an animal model for cognition dysfunction) using one trail step down type of
      passive avoidance and elevated plus maze tasks, respectively. Aged or chronic
      ethanol-treated mice showed poor retention of memory in step-down passive
      avoidance and in elevated plus-maze task. Chronic administration of quercetin
      (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v,
      2g/kg per orally) for 24 days significantly reversed the age-related or chronic
      ethanol-induced retention deficits in both the test paradigms. However, in both
      memory paradigms chronic administration of quercetin failed to modulate the
      retention performance of young mice. Chronic quercetin administration for 30 days
      also reversed age associated increase in TBARS levels and decline in forebrain
      total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration
      to young mice produced an increase in lipid peroxidation, and a decline in
      forebrain total glutathione (GSH), SOD and catalase levels, which was
      significantly reversed by the co-administration of quercetin (10, 25 and 50
      mg/kg). The results of the present study showed that chronic quercetin treatment
      reverses cognitive deficits in aged and ethanol-intoxicated mice, which is
      associated with its antioxidant property.

PMID- 14703738
TI  - The Sabiston heritage: excellence in surgical education.

PMID- 14703739
TI  - The Duke Surgical Residency under Sabiston: comments.

PMID- 14703740
TI  - David C. Sabiston, "The Man," on the education of medical students: thereby comes
      the future of surgery.

PMID- 14703741
TI  - The Sabiston vision of basic science in a department of surgery.

PMID- 14703742
TI  - Basic science in a department of surgery.

PMID- 14703743
TI  - Surgical textbooks: past, present, and future.
AB  - The Sabiston Textbook of Surgery and other classic textbooks have been invaluable
      resources for generations of surgeons. Although they play an important role in
      medical education, printed textbooks often cannot meet the daily information
      needs of practicing surgeons because they are inaccessible, incomplete,
      unstructured, and out of date. Advances in communication technology have
      radically changed the creation and distribution of medical information. Many
      clinicians now seek evidence to support clinical decisions on the Internet and
      handheld devices. This article describes the evolution of surgical textbooks from
      printed volumes to versatile collections of knowledge that serve as both
      comprehensive resources and question-answering tools.

PMID- 14703744
TI  - Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous
      polyposis: historical development and current status.
AB  - In summary, the history and development of the proctocolectomy and ileal pouch
      anal anastomosis has involved innovative animal and clinical research by several
      surgical investigators. This evolution followed the classic process of academic
      surgical progress: a clinical problem is identified; solutions are studied in the
      laboratory; and these solutions are applied back to the clinical situation with
      success. Dr. Sabiston's disappointment with clinical results in ulcerative
      colitis and familial polyposis patients led to laboratory experiments in which a
      new technique was shown safe in dogs. The further work of his collaborator Dr.
      Ravitch as well as that of Sir Alan Parks and Dr. Utsunoimya proved small-scale
      clinical application of the new technique. Finally, large-scale outcomes work by
      Dr. Fazio at the Cleveland Clinic Foundation and others has allowed further
      refinements to occur and has highlighted other areas to study. The work of these
      investigators and other has allowed lack of a permanent ostomy with satisfactory
      functional results in more than 95% of patients. Continued experience with these
      procedures has and will lead to further improvements in operative times,
      morbidity rates, and functional results. Although research in this area will
      continue, the evolution of this operation has allowed it to become the gold
      standard for the treatment of ulcerative colitis and familial adenomatous
      polyposis.

PMID- 14703745
TI  - Portal hypertension: from Eck's fistula to TIPS.
AB  - The treatment options for portal hypertension have expanded greatly in the past 2
      decades. More selective use of surgical shunts, improvement in pharmacologic
      therapy, development of endoscopic variceal ligation, and the maturing of liver
      transplantation using both cadaveric and living donors has allowed better results
      to be achieved. A multidisciplinary, integrated approach to this clinical problem
      is needed to assure optimal outcomes.

PMID- 14703746
TI  - The changing face of abdominal aortic aneurysm management.
AB  - In summary, endovascular therapy represents a new and exiting paradigm in the
      treatment of abdominal aortic aneurysms. Its detractors have now largely been
      silenced, and a working knowledge of the devices and techniques is essential for
      all surgeons who care for patients with aneurysms. The first 25,000 stent-graft
      procedures have been attended by significant risks of implantation and endoleak,
      but the patients' acceptance of the technique has been heard loud and clear. The
      surgeon's task is not to convince the patient to undergo a more painful and
      invasive open procedure, but to advance the understanding, design, and
      implementation of this new technique such that its long-term results will someday
      rival those of the time-tested traditional operation.

PMID- 14703747
TI  - Pulmonary embolism.

PMID- 14703748
TI  - Organ transplantation: what is the state of the art?

PMID- 14703749
TI  - Gene therapy in cardiovascular disease: state of the art.

PMID- 14703750
TI  - Cerebral protection in infant cardiac surgery.

PMID- 14703751
TI  - Minimally invasive cardiac surgery.

PMID- 14703752
TI  - Minimally invasive cardiac surgery.

PMID- 14703753
TI  - Surgical perspectives on aortic valve endocarditis.

PMID- 14703754
TI  - Commentary on surgical perspectives on aortic valve endocarditis: an interview
      with Dr. W. Glenn Young Jr, Professor Emeritus, Duke University Medical Center,
      Interview by Ashish S. Shah.

PMID- 14703755
TI  - Pancreatic cancer since Halsted: how far have we come and where are we going?

PMID- 14703756
TI  - Inguinal hernia: an old condition with new solutions.
AB  - OBJECTIVE: To review the recent surgical advances in the treatment of inguinal
      hernias. SUMMARY BACKGROUND DATA: Traditional tissue-based techniques (eg,
      Bassini, McVay, Shouldice) characterized the armamentarium of the inguinal hernia
      surgeon during the 1970s and early 1980s. With the need to reduce the rate of
      hernia recurrence, as well as postoperative pain and convalescence, the treatment
      of inguinal hernias underwent a dramatic evolution over the past 15 years. The
      major advances included the introduction of the concept of tension-free hernia
      surgery, the use of prosthetic materials, and the development of laparoscopic
      techniques. RESULTS: The recognition that excessive suture-line tension was
      primarily responsible for high recurrence rates and significant postoperative
      pain following tissue-based repairs led to the introduction of the concept of
      tension-free hernia surgery. The development of prosthetic materials ushered in
      the current era of hernia surgery, allowing a tension-free repair to be performed
      even for the largest defects and the most difficult procedures. Tension-free mesh
      based repairs (eg, Lichtenstein, plug and patch) began to increase in number in
      the late 1980s. More recently, with the advent of laparoscopy for general
      surgery, various laparoscopic techniques have been developed for inguinal hernia
      repair, including the transabdominal preperitoneal repair, the intraperitoneal
      onlay mesh repair, and the totally extraperitoneal repair. CONCLUSIONS: Today,
      open and laparoscopic mesh-based techniques dominate the inguinal hernia repair
      marketplace. The Lichtenstein tension-free mesh onlay repair is the most
      frequently performed inguinal hernia operation, with a recurrence rate of less
      than 1%. Although the use of laparoscopic techniques for bilateral or recurrent
      hernias is now accepted, the application of laparoscopy to unilateral primary
      inguinal hernias remains controversial. Ongoing studies will address the
      questions of long-term recurrence and cost-effectiveness of laparoscopic hernia
      repair.

PMID- 14703757
TI  - Implant-enhanced tooth movement: indirect absolute anchorage.
AB  - Four case reports demonstrate the effectiveness of indirect anchorage in
      orthodontics. These cases demonstrate the variety of situations in which absolute
      anchorage can be applied. A maxillary premolar extraction case illustrates the
      effectiveness of anterior retraction with this technique. A maxillary posterior
      protraction case shows the ease with which space closure can be achieved. Dual
      arch capability is demonstrated through a four-premolar extraction case. Lastly,
      a case of severe dental mutilation devoid of any anchor units under conventional
      methods depicts how effectively distal driving can be accomplished. The technique
      involves the simple placement of a midpalatal endosseous implant that provides
      anchorage by indirect means to various teeth by virtue of a transpalatal arch
      soldered to its abutment. Once stabilized by such means, dramatic movements can
      be achieved in situations that would otherwise overtax anchor units and result in
      loss of anchorage. Teeth that would otherwise require stepwise and sequential
      movements can be mobilized en masse, greatly simplifying mechanotherapy and
      dramatically shortening treatment time. When no longer needed, the palatal
      implant is explanted and leaves no permanent deformation or defect after 2 or 3
      weeks of healing.

PMID- 14703758
TI  - Porcelain versus composite inlays/onlays: effects of mechanical loads on stress
      distribution, adhesion, and crown flexure.
AB  - This study used 2-D finite element modeling to simulate cuspal flexure and
      stresses at the surface and tooth-restoration interface of a restored maxillary
      molar using three restorative materials; the influence of four inlay/onlay
      preparation configurations on stress distribution within the complex was also
      investigated. A buccolingual cross-section of an intact molar was digitized and
      used to create 2-D models restored with different restorative materials
      (feldspathic porcelain, high- and low-elastic modulus composites) and tooth
      preparations (small and large inlays, small and large onlays). Two simulated 25-N
      oblique loads were applied to the cusps. The tangential stress for each finite
      element node located at the tooth surface, interfacial stress, and relative
      cuspal flexure were analyzed. All materials and tooth preparations exhibited
      similar surface tangential stress patterns, with a definite compressive area at
      the external cusp ridges, a tensile zone at the occlusal surface, and compression
      stress peaks at the CEJ. The low-elastic modulus composite showed reduced tensile
      stresses at its surface but increased tension at the dentin-adhesive interface
      when compared to ceramics. All types of onlays demonstrated a majority of
      compressive interfacial stresses, while inlays showed a majority of tensile
      stresses. The interfacial tension at the dentin level increased with the
      flexibility of the restorative material. Only the large ceramic onlay displayed
      almost pure compression at the interface. Composite-restored teeth exhibited
      increased crown flexure, while porcelain-restored teeth showed increased crown
      stiffness. Porcelain inlays/onlays featured more detrimental stresses at the
      occlusal surface but better potential protection against debonding at the dentin
      restoration interface compared to composite inlays/onlays. Ceramic
      onlays/overlays seem to represent an effective answer to restore severely damaged
      posterior teeth.

PMID- 14703759
TI  - Sinus/alveolar crest tenting (SACT): a new technique for implant placement in
      atrophic maxillary ridges without bone grafts or membranes.
AB  - An adequate amount of bone, in both width and height, is required for successful
      implant placement. When alveolar ridges are severely resorbed, the bone volume
      must be increased before implants may be placed. A variety of grafting techniques
      that successfully remedy this limitation have been developed, but they often
      require multiple surgical procedures and a prolonged healing time. This article
      describes the sinus/alveolar crest tenting technique, which permits successful
      implant placement in the severely atrophic posterior maxilla without bone grafts
      or membranes. Clinical healing is complete after 6 months.

PMID- 14703760
TI  - Patient preference for ultrasonic or hand instruments in periodontal maintenance.
AB  - The purpose of this study was to determine if patients prefer ultrasonic or hand
      instruments for periodontal maintenance. A questionnaire of 13 items was answered
      by 469 patients in three periodontal offices. The results showed a strong
      preference (74%) for ultrasonic instruments. The possibility of increased
      compliance because of this preference is discussed.

PMID- 14703761
TI  - Histologic evaluation of connective tissue grafts in humans.
AB  - The goal of this study was to evaluate the histologic composition of connective
      tissue grafts removed from the area palatal of the first molar through the
      premolars. In spite of attempts to remove the epithelium, it remained in 24 of 30
      grafts (80%). The incisal portion of the connective tissue graft was comprised of
      lamina propria. The mean depth of the lamina propria was 3.2 mm (65.2% of the
      graft). Apical to the lamina propria was the submucosa, which was primarily
      composed of adipose tissue. The mean depth of the submucosa was 2.0 mm (34.8% of
      the graft). There was no statistically significant difference in the composition
      of the grafts based on smoking or age. The grafts were successful in producing
      root coverage. There were 27 patients with Class I or II recession defects in
      this study; this group had a mean root coverage of 97.9%. This study demonstrated
      that most connective tissue grafts are not uniform in composition and quite often
      contain some epithelium. However, all of the grafts were clinically usable and
      produced a clinically successful result.

PMID- 14703762
TI  - Buccal and coronal bone augmentation using forced eruption and buccal root
      torque: a case report.
AB  - The following case report describes the buccal and coronal bone augmentation
      around an irretrievable tooth using forced eruption and buccal root torque for
      immediate nonsubmerged implant placement. A mandibular left second premolar with
      degree 2 mobility, severe buccal bone resorption, and interproximal angular bony
      defects was subjected to forced eruption and buccal root torque. Five months
      after this process, the tooth was displaced 15 mm coronally and the root apex
      faced buccally. Buccal and coronal bone augmentation and soft tissue enlargement
      were evident at reentry surgery. This technique enabled proper implant placement
      in a situation where the bone was compromised.

PMID- 14703763
TI  - The "Loma Linda pouch": a technique for repairing the perforated sinus membrane.
AB  - A technique, the "Loma Linda pouch," is introduced for repairing the perforated
      maxillary sinus membrane during sinus grafting procedures. A collagen membrane is
      placed against the perforated site and subsequently covers the internal surface
      of the maxillary sinus. The collagen membrane is then folded along the lateral
      access window to form a pouch that surrounds and isolates the graft material.

PMID- 14703764
TI  - GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 2:
      Clinical results.
AB  - Ninety sites were treated by sinus augmentation therapy using only Bio-Oss (31
      sites) or extraction socket and ridge augmentation therapy using only Bio-Oss
      beneath secured resorbable or titanium-reinforced nonresorbable membranes (59
      sites). The results of core biopsies taken at different intervals were discussed
      in part 1 of this study. A discussion of the use of resorbable versus reinforced
      nonresorbable membranes as a function of defect morphology is undertaken in part
      2. Secured titanium-reinforced membranes were shown to be the most ideal means by
      which to ensure the final morphology of the regenerated hard tissues.

PMID- 14703765
TI  - Surgical treatment of gingival recessions using emdogain gel: clinical procedure
      and case reports.
AB  - This article describes the clinical procedure and outcome of surgical treatment
      of gingival recessions with the adjunctive use of Emdogain gel, an enamel matrix
      derivative bioactive material for periodontal reconstructive surgery. Six cases
      with gingival recession on maxillary canines are presented with 12 months of
      follow-up. Initial gingival recession averaged 4.8 mm, with a mean probing pocket
      depth of 2.2 mm. At the 12-month follow-up, a mean of 3.5 mm of root coverage was
      observed (ie, 73% root coverage, range 60% to 100%). Probing pocket depth
      averaged 1.7 mm, indicating a 4-mm gain of clinical attachment (range 3 to 5 mm).
      On a clinical level, mucogingival surgery in combination with the application of
      Emdogain gel results in predictable root coverage and gain of clinical attachment
      while maintaining shallow pockets.

PMID- 14703766
TI  - Individual skeletal models and preoperative simulation in advanced
      osseointegration: a case report.
AB  - This article presents a new diagnostic and simulative method, PSM LAB-MACHINE,
      with the aim of the anatomic reproduction of skeletal components of the facial
      skeleton. The importance of surgical predetermination with the possibility of
      simulating the planned surgical strategies is here evaluated. The described
      clinical case demonstrates the importance of planning in the reconstructive
      surgery of the maxillofacial district, using solid structures as individual
      skeletal models. The usefulness of a solid structure as skeletal replica for the
      effectiveness of modeling corticocancellous bone grafts from the iliac crest with
      an impressive reduction of the work times is highlighted. The high precision of
      adaptation of grafts to the donor site after modeling is notable.

PMID- 14703767
TI  - Ocular expression of vascular cell adhesion molecule (VCAM-1) in 2-butoxyethanol
      induced hemolysis and thrombosis in female rats.
AB  - We demonstrated previously that exposure of rats to 2-butoxyethanol (BE) was
      associated with morphological changes in red blood cells, hemolytic anemia, and
      disseminated thrombosis and infarction in different organs including the eyes. In
      order to elucidate the mechanism of thrombosis formation, we examined in this
      study the histology and immunohistochemical expression of vascular cell adhesion
      molecule-1 (VCAM-1), endothelial intercellular adhesion molecule-1 (ICAM-1), and
      P-selectin in the eyes of the female F344 rat exposed to 2, 3, or 4 daily doses
      of BE/250 mg/kg body weight. In this BE hemolysis and thrombosis model, positive
      VCAM-1 expression occurred only in eyes of rats exposed to 3 and 4 doses and was
      localized in the iris (epithelium lining the posterior surface, anterior
      mesenchymal epithelium), ciliary processes (lining epithelium, stromal cells),
      and retina (hypertrophic retinal pigment epithelium). Only weak immunolabeling
      was seen in eyes exposed to 2 doses. The appearance of VCAM-1 immunostaining
      correlated with the development of thrombosis located in the same structures. No
      change in ICAM-1 or P-selectin expression was seen. This immunolabeling
      distribution suggests that VCAM-1 functions in the pathogenesis of BE-related
      thrombosis by promoting adhesion of erythrocytes to the endothelium.

PMID- 14703768
TI  - Effects of epithelial growth factor receptor (EGFR) kinase inhibitors on
      genetically reconstituted mouse mammary glands.
AB  - The aim of the study was to determine the effects of a specific epithelial growth
      factor Receptor kinase inhibitor (EGFR-KI) and Taxol on tumor growth in a novel
      tumor model. MATERIAL & METHODS: A genetically engineered tumor model which uses
      "transgenic" organs in immune competent mice was used. NeuT-transfected
      immortalized HC11 epithelial cells and primary mouse mammary epithelial cells
      have been transplanted into the gland-free mammary fat pad of female BALB/c mice.
      Mammary tumors developed after a latency period of three to four weeks. The mice
      were thereafter daily orally treated over a 19 or 22-day period with 0, 38, 75, 2
      x 75 mg/kg body weight (b.w.) EGFR-KI (n: 7-9 per group) or intravenously with 10
      mg/kg b.w. Taxol. After necropsy the histopathological evaluation of the tumors
      was performed in a coded manner. The proliferation activity of tumor cells was
      analyzed by laser scanning cytometry (LSC) using anti-Ki67-antibodies. RESULTS:
      Oral Treatment with EGFR-KI in this transgenic organ model showed clear antitumor
      efficacy in a dose-dependent manner in the range between 38 and 75 mg/kg b.w.
      This antiproliferative effect appears to be minimally increased at 75 mg/kg/day
      twice per day. For all treatments a strong correlation between the biological
      behavior of the tumor, histopathology and cell proliferation could be
      established. In contrast, treatment with Taxol showed no significant reduction of
      tumor growth or cell proliferation in this model. This new transgenic organ model
      comprising histopathological evaluation and cell proliferation analysis appears
      to be a suitable test system for drug candidates that affect specific biochemical
      pathways. It may have greater predictive nature for clinical effects in humans as
      compared to conventional tumor models because of its c-erb B2 gene
      overexpression.

PMID- 14703769
TI  - Antioxidants suppress nitrofurazone-induced proliferation of hepatocytes.
AB  - On administration to rats at a subtoxic dose, the antibiotic nitrofurazone (NF)
      has been shown to increase hepatocyte DNA synthesis and liver weight in a dose
      dependent manner, with no histological or biochemical evidence of cell damage or
      necrosis. Free radicals are implicated in NF metabolism, as well as in the DNA
      synthesis or cell proliferation induced by a number of other chemicals. In the
      present study, NF was given alone or concomitantly with the antioxidants N
      acetylcysteine or cyanidanol. Antioxidants prevent the effects of free radicals.
      Co-administration decreased hepatocyte proliferation to the same level as the
      control. This suppression of NF-induced hepatocyte proliferation by antioxidants
      therefore strongly suggests that free radical production is involved in this
      process.

PMID- 14703770
TI  - Decreased survival of prostate cancer cells in vitro by combined treatment of
      heat and an antioxidant inhibitor diethyldithiocarbamate (DDC).
AB  - The aim of this study was to examine a modulation of thermotolerance by treatment
      with combination of heat and the antioxidant inhibitor diethyldithiocarbamate
      (DDC) of the PC-3 prostate cancer cells. To determine thermotolerance, cells were
      heated once or twice. Two 1 h exposures at 43 degrees C, with a recovery period
      in between, revealed better survival/recovery of cells after the second exposure
      than after the first (fig. 1A + 1B). Additional experiments were performed,
      heating cells twice (fig. 1B + 1C). First, cells were heated at 43 degrees C for
      1 h and, after various recovery times (intervals) at 37 degree C, subsequently
      reheated at 44 degrees C for 1 h. To ensure effective cell killing, efficiency of
      the combined treatments of 1 mM DDC and heating at 43 or 44 degrees C for 1 h was
      estimated by measuring cell survival, reactive oxygen species (ROS) generation,
      superoxide dismutase (SOD) activity and heat shock protein 70 (hsp 70)
      expression. To obtain a more effective method for subsequent heat exposure, cells
      were heated twice after a 24 h interval in the presence or absence of 1 mM DDC.
      ROS generation and SOD activity immediately increased correlating with duration
      of heating, but their levels gently decreased with time after discontinuation of
      heating. On the other hand, hsp 70 levels slowly increased, also correlating with
      duration of heating but continued to increase with time after discontinuation of
      heating for a certain period. DDC administration coupled with heating at 43 or 44
      degrees C significantly decreased cell survival compared to heating alone (p <
      0.05). Furthermore, significant decreases in numbers of viable cells were
      observed for cells after the first heat exposure when combined with DDC as
      compared to heat alone at 43 and 44 degrees C (p < 0.05). These findings suggest
      that heat combined with DDC could have potential benefits in the treatment of
      prostate cancer.

PMID- 14703771
TI  - Evidence for the involvement of TGF-beta and PDGF in the regulation of prolyl 4
      hydroxylase and lysyloxidase in cultured rat lung fibroblasts.
AB  - Lung fibrosis is the end-point of numerous lung disorders induced by a pneumonia
      or by a variety of different noxes, one of which is the cytostatic drug bleomycin
      (BLM). Fibrosis is characterized by excessive extracellular matrix accumulation.
      Macrophage-fibroblast interactions are suggested to play an important role in the
      development of this disease. The present study was addressed to investigate one
      possible pathway of this interaction, the influence of soluble mediators produced
      by BLM-stimulated macrophages on lung fibroblast collagen synthesis and
      modification. Conditioned media (CM) of BLM-exposed macrophages of the cell line
      NR8383 submitted to rat lung fibroblast cultures increased the activity of prolyl
      4-hydroxylase (P4H) in fibroblasts in a dose dependent manner. CM of stimulated
      macrophages increased the collagen concentration in fibroblast culture
      supernatant. The level of mRNAs specific for the alpha-subunit of P4H and that
      for alpha1(I) collagen were found to be increased by about two-fold, that for
      lysyloxidase (LO) by about 2.5-fold in fibroblasts cultured in CM of stimulated
      macrophages. Pre-incubation of CM of BLM-exposed macrophages with neutralizing
      antibodies against TGF-beta or against PDGF resulted in a partial reversal of the
      increasing effect of the CM on P4H- and LO-activities in fibroblasts. Both growth
      factors, TGF-beta and PDGF, added to fibroblast cultures led to significant
      increases of P4H activity in the treated cells. We conclude that TGF-beta and
      PDGF produced by stimulated macrophages are involved in the regulation of the
      expression of alpha1(I) collagen, of P4H-alpha-subunit and LO in lung
      fibroblasts. The results indicate that this is not a direct effect but involves
      the action of a so far unidentified mediator responsible for autocrine
      stimulation of collagen production.

PMID- 14703772
TI  - Lymphocyte migration into different lung compartments during an antigen induced
      inflammation: is the spleen a major reservoir of these lymphocytes?
AB  - The hypothesis was tested whether lymphocytes of immunized and pulmonary
      challenged LEW rats adhere in higher numbers to the lung vascular bed than
      control lymphocytes and whether these immigrating cells come from the spleen. The
      kinetic of a primary immune response to sheep red blood cells (SRBC) was
      characterized in different lung compartments such as the vascular marginal pool,
      the interstitium and the bronchoalveolar space. The adherence of genetically
      labeled splenocytes from SRBC-immunized and challenged rats and from non
      challenged rats was investigated in challenged lungs using the ex vivo system of
      the isolated buffer-perfused lung (IPL). Furthermore, immunized animals were
      splenectomized and challenged with SRBC. It was found that lymphocytes were
      increased with a maximum in the lung interstitium on day 3 and in the
      bronchoalveolar lavage fluid (BALF) on day 4. The adhesion to the pulmonary
      vascular endothelium of splenic T cells from SRBC-immunized rats in the IPL was
      not significantly increased compared to those from control animals. A significant
      transmigration from the vasculature into the BALF was not found. On day 4 after
      challenge the cell numbers in the lung compartments of the splenectomized animals
      were comparable to controls. The spleen alone has no significant role as a source
      of lymphocytes in lung inflammation. Therefore, the pulmonary immune response
      seems to be triggered mainly by the local environment and not by the accompanying
      systemic immune reaction.

PMID- 14703773
TI  - Effects of intrarectal and intraperitoneal N(G)-nitro-L-arginine methyl ester
      treatment in 2,4,6-trinitrobenzenesulfonic acid induced colitis in rats.
AB  - Inflammatory bowel disease (IBD) has been associated with an increased generation
      of nitric oxide (NO). Different authors have shown that NO in IBD can be either
      harmful or protective. The aim of this study was to investigate the efficiency of
      intrarectal (i.r.) and intraperitoneal (i.p.) application of N(G)-nitro-L
      arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor,
      in experimental acute colitis in the rats. Acute colitis was induced in rats by
      2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were
      divided into four groups. L-NAME (50 mg/kg/day) was administered i.p. (Group 1)
      and i.r. (Group 2) for 7 days following the day when colitis was induced. Group 3
      rats were not given any treatment after induction of colitis. Control group rats
      were given saline solution i.r. instead of TNBS. The presence of hyperemia,
      inflammation and ulcer was evaluated to score of macroscopic morphologic damage.
      The severity of colitis was assessed by microscopic criteria including
      ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal
      atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal
      tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were
      measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both
      i.p. and i.r. L-NAME treatment significantly reduced serum and rectal tissue
      nitrite levels, but no effect on MPO activity and histologic damage score was
      observed. Under the present conditions we concluded i.r. and i.p. L-NAME
      treatment, applied at the dosage of 50 mg/kg/day, does not have any protective
      effect on the colonic injury.

PMID- 14703774
TI  - Methimazole prevents stress and chemical induced gastropathy in rats.
AB  - This investigation was undertaken to study the effect of methimazole (MMI) on
      gastric acid secretion and stress and chemically induced gastric ulcer in rats.
      Acid secretion studies were undertaken using pylorus-ligated rats pretreated with
      MMI (10-100 mg/kg, i.p.). The effect of orally administered MMI on water
      immersion restraint (WIR) stress, indomethacin and ethanol-induced gastric ulcers
      was also tested. The level of myeloperoxidase (MPO), non-protein sulfhydryls (NP
      SH) and gastric wall mucus was measured in the glandular stomach of rats
      following ethanol-induced gastric lesions. There was a dose-dependent inhibition
      of gastric acid secretion and ulcerogen induced gastric lesion formation in the
      MMI treated rats. Our morphological and histological studies showed a complete
      prevention of ethanol-induced lesions in the rats treated with high dose (100
      mg/kg) of MMI. A significant attenuation of ethanol-induced increase in gastric
      MPO activity, depletion of NP-SH and reduction of gastric wall mucus was also
      observed in MMI treated rats. These findings clearly suggest the involvement of
      endogenous pro-inflammatory agents and oxidative stress in mediating the
      gastroprotective effect of MMI.

PMID- 14703775
TI  - Strain and colony differences in the neurotoxic sequelae of MK-801 visualized
      with the amino-cupric-silver method.
AB  - The strain and sex of a species under investigation may influence the animal's
      physiological response to a variety of stimuli. Strain and sex differences are
      important considerations when evaluating animal models. In the rodent MK-801
      model of schizophrenia, degenerative changes occur widely in the main olfactory
      system and in a number of cortical brain regions. In the present report, we
      compare the effects of MK-801 neurotoxicity in two strains of female rats and
      also two lines within each strain. The magnitude and regional extent of the
      neurodegeneration detected with the amino-cupric-silver method varied markedly
      both between the Sprague-Dawley and Wistar rat strains and also between two lines
      derived from each strain. For example, terminal degeneration occurred in layer VI
      of somatosensory cortex and the central extended amygdala in Sprague-Dawley but
      not Wistar rats. Moreover, MK-801 treatment led to somatodendritic degeneration
      in the dentate gyrus of the dorsal hippocampus and basolateral amygdala in Wistar
      rats from Charles River Laboratories but not those from Ferreyra Institute. There
      are thus both strain and intrastrain differences in the magnitude of the
      neurodegenerative response to MK-801 treatment. The differing neurotoxicity of MK
      801 between rat strains and between lines within a strain may reflect genetic
      variation and/or differences in hepatic biotransformation and thus the
      bioavailability of the drug between strains and lines within a strain.

PMID- 14703776
TI  - Subcutaneous undifferentiated sarcoma induced by N'-ethyl-N'-nitrosourea in rat:
      radiology, histopathology and mutagenesis.
AB  - The aim of the present study was to investigate high dose and long-term effects
      of a common industrial agent, N'-ethyl-N'-nitrosourea (ENU), on soft tissues in a
      rat model. ENU, which was dissolved in polyethyleneglycol (PEG) was injected
      intra-peritoneally once a week (300 mg/kg) in the first experimental group. The
      second group received only PEG. The control group was free of any agent
      administration. Only rats treated with ENU for a period of 45 weeks developed
      large subcutaneous tumours (approximately 5-9 cm in size). Tumoral tissues were
      examined radiologically, histopathologically and immunohistochemically. There was
      no bone destruction beneath the soft tumoral tissues in direct X radiograms.
      Computed tomographic (CT) images showed heterogeneous soft tissue masses with a
      density ranging from 50 to 65 HU. Macroscopically, all tumors were circumscribed
      with a gray-white surface in the cross-sections. The histopathological and
      immunohistochemical examination of the subcutaneous tumoral tissues showed a
      spindle cell type of sarcoma. Lymphatic and skeletal muscle invasion, atypical
      mitoses and necroses were determined in all tumoral tissues in the experimental
      group. A somatic point mutation was detected in exon 2 of KRAS oncogene in
      sarcoma tissues using the single strand conformational polymorphism (SSCP)
      analysis. In conclusion, the activated KRAS oncogene might contribute to the
      progression of subcutaneous sarcoma in experimentally ENU induced rats due to
      point mutation.

PMID- 14703777
TI  - Effect of estradiol sulfamate (ES-J995) on affinity of hemoglobin for oxygen,
      cardiovascular function and acid-base balance in ovariectomized rats.
AB  - Oral administration of estradiol sulfamate (ES, prodrug of estradiol) leads to
      increased systemic and reduced hepatic effects than estradiol because ES is
      accumulated in erythrocytes. However, possible alterations of erythrocytic oxygen
      transport by intraerythrocytic ES accumulation has not been studied. Therefore,
      ovariectomized adult female rats (n = 58; body wt.) were randomly treated orally
      either with single doses (day 1) or multiple dose (days 1-4) with vehicle, with
      estradiol sulfamate (ES-J995, 1 mg x kg(-1) b.w.) or with estradiol (30 mg x kg(
      1) b.w.). Under general anesthesia arterial blood pressure, heart rate, blood
      gases, and acid-base balance were measured. Hypoxia was performed by lowering the
      inspired fraction of oxygen from 0.35 to 0.12. In addition, individual oxygen
      dissociation curves and ES-J995 distribution in blood and plasma were estimated.
      ES-J995 was accumulated in erythrocytes by approximately 98% (P < 0.01), but
      oxygen transport capacity was not altered (P50: 35.6 +/- 1.0 mm Hg to 37.1 +/-
      1.1 mm Hg). Blood gases and acid-base balance parameters were not altered after
      ES-J995 treatment under normoxic and hypoxic conditions. In conclusion, ES-J995
      accumulation in erythrocytes does not alter the affinity of hemoglobin for oxygen
      nor any function which would indicate an impaired oxygen delivery to the body.

PMID- 14703778
TI  - Experimental cadmium poisoning in sheep.
AB  - Pathomorphological investigations of internal organs were made in sheep given
      sublethal doses of cadmium. Early histological damages in kidneys were
      established by renal biopsy in some experimental animals. The main histological
      changes were characterized by granular degeneration in proximal tubules and
      glomerular endothelial proliferation in kidneys, granular degeneration in
      hepatocytes, pericapillary oedema and activation of capillary endothelium and
      Kupffer cells in liver, oedematous and degenerative changes in cerebrum and in
      the region of Purkinje cells of cerebellum, hyperplasia and proliferation of
      alveolar epithelium and perivascular or peribronchial mononuclear cell
      infiltration in lung, and degenerative changes in the medulla and zona
      glomerulosa of adrenal glands.

PMID- 14703779
TI  - The ESTP Award 2003 including 1,000 EUR is given in equal parts to Dr. Juliette
      Lilbert and Dr. Daniel Robert Roth.

PMID- 14703780
TI  - Completeness of state administrative databases for surveillance of congenital
      heart disease.
AB  - BACKGROUND: Tracking birth prevalence of cardiac defects is essential to
      determining time and space clusters, and identifying potential associated
      factors. Resource limitations on state birth defects surveillance programs
      sometimes require that databases already available be used for ascertaining such
      defects. This study evaluated the data quality of state administrative databases
      for ascertaining congenital heart defects (CHD) and specific diagnoses of CHD.
      METHODS: Children's Hospital of Wisconsin (CHW) medical records for infants born
      1997-1999 and treated for CHD (n = 373) were abstracted and each case assigned
      CHD diagnoses based on definitive diagnostic reports (echocardiograms,
      catheterizations, surgical or autopsy reports). These data were linked to state
      birth and death records, and birth and postnatal (< 1 year of age) hospital
      discharge summaries at the Wisconsin Bureau of Health Information (WBHI).
      Presence of any code/checkbox indicating CHD (generic CHD) and exact matches to
      abstracted diagnoses were evaluated. RESULTS: Fifty-eight percent of cases with
      generic CHD were identified by state databases. Postnatal hospital discharge
      summaries identified 48%, birth hospital discharge summaries 27%, birth
      certificates 9% and death records 4% of these cases. Exact matches were found for
      52% of 633 specific diagnoses. Postnatal hospital discharge summaries provided
      most matches. CONCLUSION: State databases identified 60% of generic CHD and
      exactly matched about half of specific CHD diagnoses. The postnatal hospital
      discharge summaries performed best in both in identifying generic CHD and
      matching specific CHD diagnoses. Vital records had limited value in ascertaining
      CHD.

PMID- 14703781
TI  - Estimating prevalence of fetal alcohol syndrome (FAS): effectiveness of a passive
      birth defects registry system.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) is a preventable birth defect, easiest
      to recognize in children two through eleven years and more difficult to recognize
      in newborns. In New York State, two systems ascertain FAS cases, the statewide
      birth defects registry and the Fetal Alcohol Syndrome Surveillance Network
      (FASSNet) system. The accuracy of FAS reports to the birth defects registry was
      assessed through a comparison with the FASSNet system. METHODS: The birth defects
      registry mandates reporting up to age two, including FAS with an ICD-9 code of
      760.71. FASSNet is a population-based, multi-source surveillance and uses a
      standard definition to determine FAS case status. RESULTS: Among 33 children
      reported to the registry with FAS, 19 (58%) met FASSNet criteria for FAS. FASSNet
      identified 24 additional children with FAS facial features documented before the
      child's second birthday that should have been reported to the birth defects
      registry. FAS prevalence rate for the birth defects registry was 0.28 per 1,000
      live births but would have been 0.37 if all children diagnosed before age two
      were included. CONCLUSIONS: Almost 60% of children reported to a birth defects
      registry with FAS from 1995 to 1998 were confirmed as FAS based on a more
      intensive surveillance. Additional children with FAS were not reported to the
      CMR. FAS prevalence calculated from birth defects registries, relying on the ICD
      9 code 760.71, include false positives and underestimate the true prevalence. Age
      limits for reporting FAS to registries further contribute to under ascertainment.

PMID- 14703782
TI  - Random error and undercounting in birth defects surveillance data: implications
      for inference.
AB  - BACKGROUND: There has been an ongoing debate among birth defects investigators
      about whether or not to publish estimates of rates of birth defects with
      confidence intervals to allow for comparisons of rates across regions and time. A
      major impediment in resolving this debate has been the lack of a framework for
      quantifying uncertainties in the data that can be applied uniformly to birth
      defects surveillance programs. This report presents an overview of random error
      and ascertainment bias in birth defects surveillance data, and of the
      implications of these errors for estimation and comparisons of birth defects
      rates. METHODS: We consider when confidence intervals can be used as part of a
      strategy to make inference on rates, as well as ratios of or differences between
      two rates. Worth noting is that confidence intervals only address random error in
      the data. In the presence of undercounting of cases, estimation of rates and
      confidence intervals requires knowledge or an estimate of the extent of
      underascertainment. Rate estimates and confidence intervals that ignore such bias
      can be misleading. However, if it is reasonable to assume that the ascertainment
      bias is constant over time (or across regions), then it is possible to make valid
      comparisons of rates over time (or across regions) using ratio or difference
      estimators, even when lack of knowledge of the extent of undercounting makes
      estimating the absolute rate and its confidence interval problematic. Finally,
      sensitivity analyses can use confidence limits to determine the difference in
      ascertainment bias necessary to explain an apparent difference in rates.
      CONCLUSION: Because birth defects surveillance systems have evolved in the
      absence of agreed upon standards to guide the process, it is difficult to
      determine the extent to which the variability in rates of birth defects across
      programs or over time is real or due to differences in surveillance methods.
      Efforts to develop standards for birth defects surveillance may help to minimize
      the variability in prevalence of birth defects due to differences in case
      ascertainment methods and allow for evaluations of real temporal and spatial
      variations in environmental effects. In the meantime, if comparisons of rates
      need to be made to address public health concerns, it would be prudent to conduct
      only such comparisons between regions or across time when the degree of case
      ascertainment can be assumed to be relatively constant across regions and time.

PMID- 14703783
TI  - The Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects
      surveillance at the Centers for Disease Control and Prevention.
AB  - BACKGROUND: The Metropolitan Atlanta Congenital Defects Program (MACDP) is a
      population-based birth defects surveillance program administered by the Centers
      for Disease Control and Prevention (CDC) that has been collecting, analyzing, and
      interpreting birth defects surveillance data since 1967. This paper presents an
      overview of MACDP current methods and accomplishments over the past 35 years.
      METHODS: MACDP actively monitors major birth defects among infants born to
      residents of five counties of metropolitan Atlanta, an area with approximately
      50,000 annual births. Cases are ascertained from multiple sources, coded using a
      modified British Pediatric Association six-digit code, and reviewed and
      classified by clinical geneticists. RESULTS: MACDP has monitored trends in birth
      defects rates and has served as a case registry for descriptive, risk factor, and
      prognostic studies of birth defects, including studies of Agent Orange exposure
      among Vietnam War veterans, maternal use of multivitamins, diabetes, febrile
      illnesses, and survival of children with neural tube defects. MACDP has served as
      a data source for one of the centers participating in the National Birth Defects
      Prevention Study, and for developing and evaluating neural tube defects
      prevention strategies related to the periconceptional use of folic acid
      supplements. CONCLUSIONS: Since its inception, MACDP has served as a resource for
      the development of uniform methods and approaches to birth defect surveillance
      across the United States and in many other countries, monitoring birth defects
      rates, and as a case registry for various descriptive, etiologic, and survival
      studies of birth defects. MACDP has also served as a training ground for a large
      number of professionals active in birth defects epidemiology.

PMID- 14703784
TI  - Maternal age-specific Down syndrome rates by maternal race/ethnicity, Hawaii,
      1986-2000.
AB  - BACKGROUND: Published maternal age-specific rates for Down syndrome are based
      mostly on populations of predominately European origin. Down syndrome rates have
      been reported to vary by race/ethnicity. The objective of this study was to
      calculate maternal age-specific Down syndrome rates for various racial/ethnic
      groups and to compare the rates between the racial/ethnic groups. METHODS: Data
      were obtained from a population-based birth defects registry and included all
      Down syndrome cases delivered in Hawaii during 1986-2000 with maternal
      race/ethnicity of white, Far East Asian, Pacific Islander, or Filipino. Maternal
      age-specific Down syndrome rates were calculated for each race/ethnicity, and the
      rates were compared. RESULTS: The pattern of maternal age-specific Down syndrome
      rates among Far East Asians and Filipinos was similar to that among whites--Down
      syndrome rates increased with maternal age, with the increase in rate being most
      obvious for maternal age groups of 35 years or greater. However, for maternal age
      of 35 years or greater, the Down syndrome rate was lower for Pacific Islanders
      than whites, with the difference between the two racial/ethnic groups being
      significant for maternal age of 40 years or greater (rate ratio 0.13, 95%
      confidence interval 0.02-0.48). CONCLUSIONS: All racial/ethnic groups do not
      appear to demonstrate the same maternal age pattern of Down syndrome rates as
      whites. This is important because maternal age-specific Down syndrome rates are
      used to calculate expected Down syndrome rates in a population and to estimate a
      woman's risk of having an infant with Down syndrome given her age.

PMID- 14703785
TI  - Omphalocele and gastroschisis in the State of New York, 1992-1999.
AB  - BACKGROUND: Variations in the temporal distribution and risk factors for
      omphalocele and gastroschisis have been suggested although results have not been
      conclusive. This study examines the trend and risk factors for both conditions
      among live births in New York State. METHODS: Analysis of surveillance data from
      the New York Congenital Malformation Registry for the years 1992-1999. RESULTS:
      Five hundred and ninety-five (595) infants with either omphalocele (287) or
      gastroschisis (308) were identified. It appeared that the prevalence of
      gastroschisis was rising from 1992-1999, while prevalence of omphalocele was
      decreasing. Cases of gastroschisis were clustered among younger mothers while the
      maternal age distribution among omphalocele infants was U-shaped. As compared to
      Whites, Black infants were more likely to present with omphalocele (OR = 1.73;
      95% confidence interval = 1.28-2.33) and Hispanic infants with gastroschisis (OR
      = 1.50; 95% CI = 1.12-2.00). For both anomalies, residents of rural New York were
      significantly at higher risk than those living in urban New York. Twenty-three
      chromosomal aberrations were detected, all among omphalocele babies. Infant
      survival was substantially greater among gastroschisis (92%) as compared to
      omphalocele newborn (81%)[p < 0.0001]. CONCLUSIONS: Prevalence of gastroschisis
      has been on the rise while that of omphalocele has been declining in New York
      State. Geographical and racial/ethnic variations were observed, further
      confirming the notion of different etiologies for the two congenital anomalies.

PMID- 14703786
TI  - Orofacial cleft malformations: associations with maternal and infant
      characteristics in Washington State.
AB  - BACKGROUND: To characterize the prevalence of orofacial cleft malformations and
      investigate variations in prevalence according to maternal and infant
      characteristics, we analyzed a cohort of 298,138 live births delivered between
      1987 and 1990 to residents of Washington State. METHODS: Infants with cleft
      defects were identified using a statewide, population-based birth defects
      registry. Information on infant and maternal characteristics was obtained from
      Washington State birth certificates. Multiple logistic regression analysis was
      used to measure the association between potential risk factors and orofacial
      clefts. Cleft lip with or without cleft palate (CL +/- CP) and cleft palate (CP)
      were analyzed separately, depending on the presence or absence of other defects.
      RESULTS: We identified 608 infants with cleft defects. The prevalences of
      isolated and non-isolated CL +/- CP were 0.87 and 0.30 per 1,000 live births,
      respectively. The prevalences of isolated and non-isolated CP were 0.34 and 0.54
      per 1,000 live births, respectively. Compared with mothers aged 25-29 years,
      mothers aged < 20 years were twice as likely to have an infant with isolated CL
      +/- CP (RR = 2.0; 95% CI 1.3, 2.9). Compared to white mothers, black mothers were
      more likely to have an infant with non-isolated CL +/- CP (RR = 2.8; 95% CI 1.2,
      6.6). CONCLUSIONS: The prevalences of orofacial clefts in Washington State in
      1987-90 were similar to those of other states. This study is among the first to
      report a greater relative risk for isolated CL +/- CP among the infants of
      mothers < 20 years compared to older mothers.

PMID- 14703787
TI  - Treatment of oralfacial clefts by state-affiliated craniofacial centers and cleft
      palate clinics.
AB  - BACKGROUND: Oralfacial clefting (OFC) disorders require expedient evaluation and
      treatment to obtain optimal outcome. In Florida, there is a statewide program
      targeted to the care of infants with OFC. We therefore sought to determine
      statewide referral and treatment patterns of children born with OFC identified
      through the Florida Birth Defects Registry. METHODS: Using data for 1996 and 1997
      and ICD-9 CM codes 749.00 - 749.25, we identified 539 OFC cases. All cases were
      matched with the evaluation and treatment records of the statewide Children's
      Medical Services' (CMS) craniofacial centers (CFC) and cleft palate clinics
      (CPC). The likelihood of CMS contact was examined with respect to demographic and
      other descriptive data characterizing the OFC cases. RESULTS: 42% (227/539) of
      OFC cases were evaluated at or known to the CFC or CPC. Children with cleft lip
      and palate were more likely to have had contact than were those with cleft lip or
      cleft palate alone. The CFC and CPC programs were most likely to provide
      evaluation between age 2 months and 3 years. Of 12 counties with occurrences of
      more than 15 OFC cases, 2 had significantly lower contact rates, suggesting
      possible problems in accessibility or reporting of services. CONCLUSIONS:
      Statewide Birth Defect Registry data can be used in collaboration with statewide
      treatment programs to gain insight into referral patterns and provision of
      services. Factors influencing access to services and quality of care, though not
      addressed by this study, could be prospectively incorporated into such a project.

PMID- 14703788
TI  - Registry to referral: using birth defects registries to refer infants and
      toddlers for early intervention services.
AB  - BACKGROUND: Although many birth defect surveillance systems were developed for
      the primary purpose of monitoring trends and conducting epidemiologic studies, a
      number of programs have recognized the potential of birth defects monitoring
      systems for identifying and referring children who may be eligible for services.
      Because almost all surveillance programs maintain a registry of all children who
      have been diagnosed with birth defects in a particular state or other defined
      geographic region, registries can play an important role in identifying eligible
      children and providing timely referral to specialized services. METHODS: We sent
      electronically an 18-question survey to the Centers for Disease Control and
      Prevention's list of State Birth Defects Surveillance Contacts in all 50 states,
      the District of Columbia, and Puerto Rico. The survey queried states as to
      whether they had or were developing a birth defect surveillance program, the
      extent to which they were currently using or were considering using their program
      as a means of identifying and referring children for services, and if so, the
      manner in which referrals were made. RESULTS: We received completed surveys from
      all 50 states, Washington, DC, and Puerto Rico. Thirty-two of the fifty-two
      respondents stated that their state or entity has an operational birth defect
      surveillance program. Of these, 13 have implemented an identification and
      referral system within the surveillance program. All 16 states that were planning
      a surveillance program are also are planning or beginning to implement a program
      that would include an identification and referral system. Respondents cited lack
      of resources and confidentiality concerns as being the major barriers to
      implementing a referral system for their registry. CONCLUSIONS: For many
      registries, using their surveillance data for program development purposes
      represents a new undertaking. This trend reflects increasing recognition of the
      role that state-based birth defect surveillance systems can play in supporting
      child-find efforts for children with special needs. In the long run, this
      expanded focus may further enhance the public health usefulness of birth defect
      surveillance programs.

PMID- 14703789
TI  - Mortality associated with birth defects: influence of successive disease
      classification revisions.
AB  - INTRODUCTION: The National Vital Statistics System is the fundamental source of
      mortality statistics in the United States. The cause-of-death classification
      which is used to assign medical terms to a standard taxonomy is revised
      periodically, and it is necessary to account for these changes when investigating
      trends. This paper presents birth defects mortality statistics and preliminary
      information on the most recent transition between revisions of the
      classification. METHODS: Descriptive statistics are presented using multiple
      cause and underlying cause counts, rankings of leading causes of death, infant
      mortality rates, and age-adjusted death rates. Comparability results are based
      upon records that have been coded using two separate classifications. RESULTS:
      Birth defects remain the leading cause of death for infants and among the leading
      causes for younger age groups. The trend for birth defect mortality shows that
      the risk of dying from birth defects decreased between 1950 and 2000. The effect
      of implementing successive revisions of the cause-of-death classification was
      relatively minor until the implementation of the most recent revision. Fewer
      records are assigned to birth defects in the latest revision than in the previous
      revision. DISCUSSION: Researchers investigating mortality trends related to birth
      defects need to be aware that the cause-of-death classification changes
      periodically. The effect of the changes between two successive classifications
      can be measured and explained.

PMID- 14703790
TI  - Mortality throughout early childhood for Michigan children born with congenital
      anomalies, 1992-1998.
AB  - BACKGROUND: Congenital anomalies are a leading cause of infant deaths, accounting
      for almost a fifth of all infant deaths. Few studies have researched the survival
      experience of infants born with congenital anomalies past the infant stage.
      METHODS: Using birth and death files routinely linked to the Michigan Birth
      Defects Registry, we identified all singleton infants during calendar years 1992
      through 1998 with reportable congenital anomalies for our study. A comparative
      file of children born without congenital anomalies during the same time period
      was developed using linked birth and death files. The mortality data were
      assessed by age at death (through age six) and race to determine mortality rates,
      relative risks, hazard ratios, and survival trends. RESULTS: Throughout early
      childhood, children born with congenital anomalies had a high risk of mortality
      compared with all other children. The overall 7-year hazard ratio comparing
      children with congenital anomalies with all other children was 7.2. Overall
      mortality rates for black children were significantly higher than white children
      through the age of seven, irrespective of whether they had congenital anomalies.
      Among children with congenital anomalies, this disparity disappeared after
      adjusting for birth weight, sex, mother's age, mother's education, and number of
      organ systems affected. CONCLUSIONS: Compared with children without congenital
      anomalies, children born with congenital anomalies had a higher risk of mortality
      well beyond the infant period. Racial disparities in mortality rates among
      children with congenital anomalies were due to confounding factors.

PMID- 14703791
TI  - First-year survival of infants born with congenital heart defects in Arkansas
      (1993-1998): a survival analysis using registry data.
AB  - BACKGROUND: In the United States and other developed nations, birth defects are
      the leading cause of infant mortality. Congenital heart defects (CHDs) are among
      the most prevalent and fatal of all birth defects. Here we report the survival
      probability of infants born with CHDs in Arkansas and examine the impact of
      multiple malformations on survival. METHODS: Birth and death certificate records
      were linked to birth defects registry data for infants born with CHDs from
      January 1993 through December 1998 in Arkansas. Both neonatal and first-year
      survival probabilities were estimated. These were computed non-parametrically
      using Kaplan-Meier's product limit method. A Cox proportional-hazards model was
      used to evaluate the relative importance of additional malformations on survival.
      RESULTS: A total of 1,983 infants with CHDs were included in this study. The
      neonatal survival probability for this cohort was 94.0% (95% CI: 93.0%, 95.1%),
      and the first-year survival probability was 88.2% (95% CI: 86.8%, 89.6%). The
      presence of hypoplastic left heart syndrome conferred the greatest reduction in
      survival, whereas infants with pulmonic valve stenosis and infants with
      ventricular septal defects had the highest first-year survival. Infants with
      multiple CHDs had decreased survival compared to those with isolated heart
      defects. Survival was also adversely affected by the presence of congenital
      abnormalities in other body systems. CONCLUSIONS: Neonatal and first-year
      survival of infants with CHDs varies by both the type of cardiac malformation and
      the presence of additional cardiac and non-cardiac malformations. Further work
      will focus on the effects of maternal and infant characteristics on survival.

PMID- 14703792
TI  - Birth defects surveillance data from selected states, 1996-2000.

PMID- 14703793
TI  - A comparison of fetal alcohol syndrome surveillance network and birth defects
      surveillance methodology in determining prevalence rates of fetal alcohol
      syndrome.

PMID- 14703794
TI  - To what end does nature produce superoxide? NADPH oxidase as an autocrine
      modifier of membrane phospholipids generating paracrine lipid messengers.
AB  - Production of superoxide anion O2*- by the membrane-bound enzyme NADPH oxidase of
      phagocytes is a long-known phenomenon; it is generally assumed that O2*-helps
      phagocytes kill bacterial intruders. The details and the chemistry of the killing
      process have, however, remained a mystery. Isoforms of NADPH oxidase exist in
      membranes of nearly every cell, suggesting that reactive oxygen species (ROS)
      participate in intra- and intercellular signaling processes. What the nature of
      the signal is exactly, how it is transmitted, and what structural characteristics
      a receptor of a "radical message" must have, have not been addressed
      convincingly. This review discusses how the action of messengers is in agreement
      with radical-specific behavior. In search for the smallest common denominator of
      cellular free radical activity we hypothesize that O2*- and its conjugate acid,
      HO2*, may have evolved under primordial conditions as regulators of membrane
      mechanics and that isoprostanes, widely used markers of "oxidative stress", may
      be an adventitious correlate of this biologic activity of O2*-/HO2*. An overall
      picture is presented that suggests that O2*-/HO2* radicals, by modifying cell
      membranes, help other agents gain access to the hydrophobic region of
      phospholipid bilayers and hence contribute to lipid-dependent signaling cascades.
      With this, O2*-/HO2* are proposed as indispensable adjuvants for the generation
      of cellular signals, for membrane transport, channel gating and hence, in a
      global sense, for cell viability and growth. We also suggest that many of the
      allegedly O2*- dependent bacterial pathologies and carcinogenic derailments are
      due to membrane-modifying activity rather than other chemical reactions of O2*
      /HO2*. A consequence of this picture is the potential evolution of the "radical
      theory of ageing" to a "lipid theory of aging".

PMID- 14703795
TI  - Porphyrin-induced photooxidation of conjugated bilirubin.
AB  - Visible light irradiation of 18 microM bilirubin ditaurate (BR-DT) at pH 7.0 for
      30 min showed a 10% decrease in absorbance at 445 nm. When the reaction was
      carried out in the presence of a trace amount of uroporphyrin (UP), the spectrum
      of BR-DT disappeared without a concomitant formation of biliverdin.
      Photooxidation products were confirmed to be dipyrrole-containing compounds.
      Photo-bleaching of BR-DT was accelerated by the increasing concentration of UP
      and was inhibited, when UP was replaced by Cu2+UP. Formation of 2,2,6,6
      tetramethylpiperidine N-oxyl through the irradiation of UP was diminished by
      sodium azide, a potent scavenger of singlet oxygen. The efficiency of singlet
      oxygen formation through visible light irradiation was in the order UP,
      coproporphyrin > Cu2+UP. Both bilirubin and BR-DT bound to human serum albumin
      (HSA) were photooxidized effectively in the presence of UP. The results indicate
      that irradiation of UP produces singlet oxygen with high efficiency which then
      rapidly oxidizes free and conjugated bilirubin.

PMID- 14703796
TI  - Transferrin modifications and lipid peroxidation: implications in diabetes
      mellitus.
AB  - Free iron is capable of stimulating the production of free radicals which cause
      oxidative damage such as lipid peroxidation. One of the most important mechanisms
      of antioxidant defense is thus the sequestration of iron in a redox-inactive form
      by transferrin. In diabetes mellitus, increased oxidative stress and lipid
      peroxidation contribute to chronic complications but it is not known if this is
      related to abnormalities in transferrin function. In this study we investigated
      the role of transferrin concentration and glycation. The antioxidant capacity of
      apotransferrin to inhibit lipid peroxidation by iron-binding decreased in a
      concentration-dependent manner from 89% at > or = 2 mg/ml to 42% at 0.5 mg/ml.
      Pre-incubation of apotransferrin with glucose for 14 days resulted in a
      concentration-dependent increase of glycation: 1, 5 and 13 micromol
      fructosamine/g transferrin at 0, 5.6 and 33.3 mmol/l glucose respectively, p <
      0.001. This was accompanied by a decrease in the iron-binding antioxidant
      capacity of apotransferrin. In contrast, transferrin glycation by up to 33.3
      mmol/l glucose did not affect chemiluminescence-quenching antioxidant capacity,
      which is iron-independent. Colorimetric evaluation of total iron binding capacity
      in the presence of an excess of iron (iron/transferrin molar ratio = 2.4) also
      decreased from 0.726 to 0.696 and 0.585mg/g transferrin after 0, 5.6 and 33.3
      mmol/l glucose, respectively, p < 0.01. In conclusion, these results suggest that
      lower transferrin concentration and its glycation can, by enhancing the pro
      oxidant effects of iron, contribute to the increased lipid peroxidation observed
      in diabetes.

PMID- 14703797
TI  - The antioxidant effects of ribonuclease inhibitor.
AB  - Ribonuclease inhibitor (RI) is an acidic cytosolic glycoprotein with molecular
      weight of about 50 kDa, which contains 32 cysteine residues. It is possibly that
      RI may have antioxidant effect by thiol-disulfide exchange reaction. We studied
      the effects of RI over-expression on the rat glial cell line C6 injured with
      H2O2. The transfected C6 cells with RI cDNA (C6') had higher viability, less LDH
      leakage and MDA contents, but more GSH contents compare that in the control C6
      cells. In transfected C6 cells, the activities of CAT and GST were higher than
      that in the control C6 cells. Without H202 stress, the activities of CAT and GST
      in the C6' cells were 1.73 and 3.62 times that in the control C6 cells,
      respectively; With 1.00 mmol/L H2O2 stress, the activities of CATand GSTin the
      C6' cells were 3.38 and 2.11 times that in the C6 cells, respectively. These
      results suggest that the over-expression RI has antioxidant activity and it is
      able to protect cells from per-oxidative injuries. Moreover, we investigated
      whether RI has a protective role against mouse hepatic damage in vivo. The mice
      pretreated with different doses of human RI were injected by CC14. The results
      show that the SOD activities of therapy groups were significantly higher than
      that of the control group (p < 0.01), while the contents of MOD and activities of
      ALT and AST in blood were remarkably lower than that of the control group (p <
      0.01). Pathological examination shows that the degree of damage was alleviated
      with RI therapy. These results suggest that RI has the protective role against
      mouse hepatic damage induced by CC14. The anti-oxidative effects of RI may play
      an important role in cell protection from per-oxidative injuries.

PMID- 14703798
TI  - Effects of phenolic compounds on reactions involving various organic radicals.
AB  - Investigation of effects produced by 26 various phenol and diphenol derivatives,
      including industrial and natural antioxidants (ionol, bis-phenol 2246, alpha
      tocopherol), on final product yields of radiation-induced free-radical processes
      involving peroxyl, alkyl, alpha-hydroxyalkyl and alpha,beta-dihydroxyalkyl
      radicals has been performed. Ionol and bis-phenol 2246 have been shown to be more
      effective than alpha-tocopherol or diphenol derivatives in suppressing
      hydrocarbon oxidation processes. At the same time, alpha-tocopherol and its water
      soluble analogues, as well as diphenol-based substances, are more effective than
      phenol derivatives in regulating various homolytic processes involving carbon
      centered radicals. This fact can be accounted for by taking into consideration
      the contribution to formation of the final product set and the respective yields
      made by semiquinone radicals and compounds with quinoid structure arising in the
      course of homolytic transformations in systems containing diphenol derivatives.

PMID- 14703799
TI  - Sensitization of U937 cells to heat shock by oxalomalate, a competitive inhibitor
      of NADP+-dependent isocitrate dehydrogenase.
AB  - Heat shock may increase oxidative stress due to increased production of reactive
      oxygen species (ROS) and/or the promotion of cellular oxidation events. Cytosolic
      NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an
      essential reducing equivalent for the antioxidant system. The protective role of
      ICDH against heat shock in U937 cells was investigated in control and cells
      treated with oxlalomalate, a competitive inhibitor of ICDH. Upon exposure to heat
      shock, the viability was lower and the protein oxidation, lipid peroxidation and
      oxidative DNA damage were higher in oxalomalate-treated cells as compared to
      control cells. We also observed the significant increase in the endogenous
      production of ROS, as measured by the oxidation of 2'7'-dichlorodihydrofluorescin
      in U937 cells treated with oxalomalate. These results suggest that ICDH plays an
      important role as an antioxidant defense enzyme in cellular defense against heat
      shock through the removal of ROS.

PMID- 14703800
TI  - Photogeneration of free radicals (*OH and HB*-) and singlet oxygen (1O2) by
      hypocrellin B in TX-100 micelles microsurroundings.
AB  - To solve the problems faced in clinical use of hypocrellins, a water-soluble
      preparation of Hypocrellin B (HB), HB-Triton X-100 (TX-100) micelles, was
      prepared. To evaluate the photodynamic activity, the free radicals (*OH and HB*-)
      and singlet oxygen (1O2) generated via photosensitization of the preparation in
      aqueous solution were detected by using electron paramagnetic resonance (EPR) and
      spectrophotometric methods. It was observed that 1O2 was formed with a quantum
      yield of 0.72, similar to that for HB in organic solvents, further, hydroxyl
      radicals (*OH) could also be efficiently produced by the new preparation, which
      have never before been detected following HB photoactivities. In addition, the
      semiquinone anion radicals (HB*-) could also be generated via the self-electron
      transfer between an excited triplet state and a ground state molecule. The
      accumulation of HB*- would replace that of *OH or 1O2 with the depletion of
      oxygen in the system. All these findings suggested that the HB-TX-100 micelles
      could play the photodynamic action through not only the type I mechanism by free
      radicals (*OH, O2*- and HB*-) but also the type II mechanism by singlet oxygen
      (1O2). It can be concluded further that the new preparation basically maintains
      the inherent photodynamic activity of HB, or even higher.

PMID- 14703801
TI  - Aminoacetone induces loss of ferritin ferroxidase and iron uptake activities.
AB  - Aminoacetone (AA) is a threonine and glycine metabolite overproduced and recently
      implicated as a contributing source of methylglyoxal (MG) in conditions of
      ketosis. Oxidation of AA to MG, NH4+, and H2O2 has been reported to be catalyzed
      by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by
      copper- and iron ion-catalyzed reactions with oxygen. We previously demonstrated
      that AA-generated O2*-. and enoyl radical (AA*) induce dose-dependent Fe(II)
      release from horse spleen ferritin (HoSF); no reaction occurs under nitrogen. In
      the present study we further explored the mechanism of iron release and the
      effect of AA on the ferritin apoprotein. Iron chelators such as EDTA, ATP and
      citrate, and phosphate accelerated AA-promoted iron release from HoSF, which was
      faster in horse spleen isoferritins containing larger amounts of phosphate in the
      core. Incubation of apoferritin with AA (2.5-50 mM, after 6 h) changes the
      apoprotein electrophoretic behavior, suggesting a structural modification of the
      apoprotein by AA-generated ROS. Superoxide dismutase (SOD) was able to partially
      protect apoferritin from structural modification whereas catalase, ethanol, and
      mannitol were ineffective in protection. Incubation of apoferritin with AA (1-10
      mM) produced a dose-dependent decrease in tryptophan fluorescence (13-30%, after
      5 h), and a partial depletion of protein thiols (29% after 24 h). The AA promoted
      damage to apoferritin produced a 40% decrease in apoprotein ferroxidase activity
      and an 80% decrease in its iron uptake ability. The current findings of changes
      in ferritin and apoferritin may contribute to intracellular iron-induced
      oxidative stress during AA formation in ketosis and diabetes mellitus.

PMID- 14703803
TI  - Dopamine and uric acid act as antioxidants in the repair of DNA radicals:
      implications in Parkinson's disease.
AB  - Dopamine (DA) and uric acid (UA) have been found to undergo a protective reaction
      effecting the fast chemical repair of oxidative free-radical damage to DNA. This
      antioxidant reaction does not occur with normal concentrations of other, more
      abundant, antioxidants and our findings suggest that DA and UA are important for
      the preservation of the DNA in certain brains cells per se. These studies point
      to the need for drugs that undergo a similar antioxidant reaction with DNA
      radicals to prevent or arrest DNA damage associated with Parkinson's disease when
      the levels of DA and UA fall.

PMID- 14703802
TI  - Factors affecting the ascorbate- and phenolic-dependent generation of hydrogen
      peroxide in Dulbecco's Modified Eagles Medium.
AB  - Ascorbate and several polyphenolic compounds have been reported to undergo
      oxidation in cell culture media to generate hydrogen peroxide (H2O2), but the
      mechanism underlying this has not been established. We therefore investigated the
      parameters affecting H2O2 production. H2O2 generation from ascorbate, gallic acid
      and other phenolic compounds in Dulbecco's Modified Eagles' Medium (DMEM) at 37
      degrees C under 95% air - 5% CO2 was not significantly inhibited by high (5-10
      mM) concentration of EGTA, o-phenanthroline or desferriox-amine, but partial
      inhibition by EDTA and diethylene-triaminepentaacetic acid (DTPA) was observed.
      Incubation of DMEM alone at 37 degrees C led to an upward drift of pH, even under
      an atmosphere of 95% air - 5% CO2. Prevention of this pH rise by increasing the
      concentration of N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] (Hepes)
      buffer lowered the levels of H2O2 generated by ascorbate and phenolic compounds,
      but there was still substantial H2O2 generated at pH 7.4. Mixtures of ascorbate
      and phenolic compounds led to less H2O2 generation than would be expected from
      the rates observed with ascorbate or phenolic compounds alone. Ascorbate
      prevented the loss of gallic acid incubated in DMEM. The role of metal ions and
      other constituents of the culture medium in promoting H2O2 generation is
      discussed.

PMID- 14703804
TI  - Damage to human erythrocytes by radiation-generated HO* radicals: molecular
      changes in erythrocyte membranes.
AB  - The effectiveness of radiation-generated HO* radicals in initiating erythrocyte
      hemolysis in the presence of oxygen and under anaerobic conditions and
      prehemolytic structural changes in the plasma-erythrocyte membrane were studied.
      Under anaerobic conditions the efficacy of HO* radicals in induction of hemolysis
      was 16-fold lower than under air. In both conditions, hemolysis was the final
      consequence of changes of the erythrocyte membrane. Preceding hemolysis, the
      dominating process under anaerobic conditions was the aggregation of membrane
      proteins. The aggregates were principally formed by -S-S- bridges. A decrease in
      spectrin and protein of band 3 content suggests their participation in the
      formation of the aggregates. These processes were accompanied by changes in
      protein conformation determined by means of 4-maleimido-2,2,6,6
      tetramethylpiperidine-N-oxyl (MSL) spin label attached to membrane proteins.
      Under anaerobic conditions, in the range of prehemolytical doses, the reaction of
      HO* with lipids caused a slight (10-16%) increase in fluidity of the lipid
      bilayer in its hydrophobic region with a lack of lipid peroxidation. However, in
      the presence of oxygen, hemolysis was preceded by intense lipid peroxidation and
      by profound changes in the conformation of membrane proteins. At the radiation
      dose that normally initiates hemolysis a slight aggregation of proteins was
      observed. Changes were not observed in particular protein fractions. It can be
      suggested the cross-linking induced by HO* radicals under anaerobic conditions
      and a lack of lipid peroxidation are the cause of a decrease in erythrocyte
      sensitivity to hemolysis. Contrary, under aerobic conditions, molecular oxygen
      suppresses cross-linking, catalysing further steps of protein and lipid
      oxidation, which accelerate hemolysis.

PMID- 14703805
TI  - Demystifying the three dimensional structure of G protein-coupled receptors
      (GPCRs) with the aid of molecular modeling.
AB  - We review our recent work on adenosine receptors, a family of GPCRs; focusing our
      attention on A3 adenosine receptor, we have demonstrated that the reciprocal
      integration of different theoretical and experimental disciplines can be very
      useful for the successful protein-based design of new, potent and selective
      receptor ligands.

PMID- 14703806
TI  - Fiber formation in water by a mono-urea dicarboxylic acid.
AB  - Fibers formed by a mono-urea dicarboxylic acid derivative in water were analyzed
      by SEM, IR and XRD. The resulting data were used to develop a model of the
      molecular aggregation leading to fiber formation.

PMID- 14703807
TI  - Fluorescence detection of guanine-adenine transition by a hydrogen bond forming
      small compound.
AB  - In combination with abasic site-containing oligodeoxynucleotides, 2-amino-4
      oxopteridine (pterin) can selectively recognize guanine base over other
      nucleobases accompanied by fluorescence quenching, which allows clear detection
      of a guanine-adenine transition with the naked eye.

PMID- 14703808
TI  - Cruciform pi-systems: hybrid phenylene-ethynylene/phenylene-vinylene oligomers.
AB  - The cruciform pentamers 3a-g were synthesized by a combined Horner-Sonogashira
      approach; their band gaps vary significantly with emission varying from blue to
      red depending upon their substituent pattern.

PMID- 14703809
TI  - High quality CdSeS nanocrystals synthesized by facile single injection process
      and their electroluminescence.
AB  - Highly luminescent CdSeS nanocrystals (quantum efficiency up to 85%), showing
      tunable luminescence properties from red to blue region with narrow band edge
      (FWHM = 34 nm), were synthesized by one-step addition of Se and S source mixture
      into the Cd precursor solution at elevated temperature, and the resulting
      nanocrystals were successfully embedded in a traditional OLED structure to give
      spectrally clean and narrow electroluminescence emission at identical positions
      of the photoluminescence spectrum.

PMID- 14703810
TI  - Excavations in molecular crystals.
AB  - Single crystals built from porous molecular networks can react with agents that
      penetrate the crystals, cleave fragments from the network, and thereby increase
      the volume available for guests, all without loss of crystallinity.

PMID- 14703811
TI  - Dehydropolymerization of arylsilanes catalyzed by a novel silylmolybdenum
      complex.
AB  - A complex [MoH3(Si(Ph)[Ph2PCH2CH2P(Ph)C6H4-o]2)] (1) can act as single-component
      catalyst for dehydrogenative polymerization of ArSiH2R (Ar = Ph, p-tolyl, o
      tolyl; R = H, Me) to (ArSiR)n: p- and o- tolylsilane produced the polymers of
      respectable molecular weights (Mw of 17300 and 6700 respectively) and
      polymerization of secondary silane, methylphenylsilane, gave a substantial
      molecular weight (Mw of 1750).

PMID- 14703812
TI  - Peroxides in ordered nanoporous silicas: clean alternatives to transition metal
      oxidants for the removal of toxic gases.
AB  - Ordered nano-structured MCM-48 silica containing sodium peroxydisulfate is a
      novel, highly effective material for the decomposition of HCN under ambient
      conditions.

PMID- 14703813
TI  - Use and recovery of a homogeneous catalyst with carbon dioxide as a solubility
      switch.
AB  - A method for fluorous biphasic catalysis is described,in which the fluorous
      liquid is replaced by fluorinated silica, the fluorous catalyst is induced to
      dissolve in the organic solvent by the presence of CO2, and the recovery of the
      catalyst after the reaction is achieved by release of the CO2 pressure.

PMID- 14703814
TI  - Multiple active oxidants in competitive epoxidations catalyzed by porphyrins and
      corroles.
AB  - We demonstrate the existence of multiple active oxygenating species in porphyrin
      and corrole-catalyzed competitive epoxidations of styrene and cis-cyclooctene.

PMID- 14703815
TI  - Hydrogen adsorption in the nanoporous metal-benzenedicarboxylate M(OH)(O2C-C6H4
      CO2) (M = Al3+, Cr3+), MIL-53.
AB  - Hydrogen adsorption has been studied in the nanoporous metal-benzenedicarboxylate
      M(OH)(O2C-C6H4-CO2) (M = Al3+, Cr3+); these solids show a hydrogen storage
      capacity of 3.8 and 3.1 wt.% respectively when loaded at 77 K under 1.6 MPa.

PMID- 14703816
TI  - Encapsulation of paramagnetic 3d1-vanadium(IV) in an antiferromagnetically
      coupled dodecanuclear copper(II) cage.
AB  - A mixed metal cluster [Cu12VO5L6] of a pentadentate Schiff base (H3L) containing
      vanadium(IV) in a dodecanuclear copper(I) cage is prepared by vanadyl templated
      self assembly of dicopper(II) precursor and the structurally characterized
      complex shows antiferromagnetic coupling involving copper(II) centers, which
      leads close to diamagnetism for the Cu(II) cage below 40 K in the presence of an
      encapsulated paramagnetic 3d1-V(IV) atom.

PMID- 14703817
TI  - Time dependent size and shape control of germanium nanocrystals.

PMID- 14703818
TI  - Poly(aniline boronic acid)-based conductimetric sensor of dopamine.
AB  - Interdigitated microelectrodes derivatized with poly(aniline boronic acid) show a
      dopamine-sensitive response at pH 7.4.

PMID- 14703819
TI  - mu4-Dicarbyne complex with a dimetallacyclobutatriene core: a new binding mode of
      C2 species.
AB  - Reaction of a permetallated ethene, (mu4-C=C)Fe2R-mu2Cp*2(CO)10, with
      diphenylacetylene affords the adduct with a new C2-binding mode, a mu4-dicarbyne
      complex, (mu4-C-C)Fe2Ru2Cp*2(CO)6(mu-Ph-C[triple bond]C-Ph), containing a
      dimetallacyclobutariene core.

PMID- 14703821
TI  - A novel isocyanide based three component reaction.
AB  - A three component reaction involving an isocyanide, a carboxylic acid and an
      epoxide or aziridine is described.

PMID- 14703820
TI  - STM images of individual porphyrin hexamers; meso-meso singly linked orthogonal
      hexamer and meso-meso, beta-beta, beta-beta triply-linked planar hexamer on
      Cu(100) surface.
AB  - Geometrical structures of chain porphyrin arrays adsorbed on Cu(100) are observed
      by STM: a bridge-like bent structure for meso-meso singly linked orthogonal
      hexamer, whereas a rigid planar and one-dimensionally stacked structure for meso
      meso, beta-beta, beta-beta triply-linked hexamer.

PMID- 14703822
TI  - Exo-metal coordination by a tricyclic [(P(mu-N-2-NC5H4))2(mu-O)]2 dimer in [(P(mu
      N-2-NC5H4))2(mu-O)]2(CuCl x (C5H5N)2)4 (2-NC5H4 = 2-pyridyl, C5H5N = pyridine).
AB  - The in situ reaction of the phosphazane dimer [CIP(mu-N-2-NC5H4)]2 (2) with CuCl
      in the presence of CsH5N/H2O gives the title complex [(P(mu-N-2-NC5H4))2(mu
      O)]2(CuCl x (C5H5N)2)4 (1), containing a tricyclic [(P(mu-N-2-NC5H4))2(mu-O)]2
      ligand which is isoelectronic with species of the type [(P(mu-NR))2NR]2.

PMID- 14703823
TI  - Control of molecular architecture by the degree of deprotonation: self-assembled
      di- and tetranuclear copper(II) complexes of N,N'-bis(2-pyridylmethyl)pyrazine
      2,3-dicarboxamide.
AB  - In the absence of added base, a deep navy-blue dimeric copper complex
      [CuII(H2L)(MeCN)]2(BF4)4 (1) of the non-deprotonated bis-terdentate diamide
      ligand H2L self-assembles whereas in the presence of base a grass-green [2 x 2]
      grid complex [CuII(HL)]4(BF4)4 (2) of the monodeprotonated ligand HL-, a rare
      example of a discrete grid of pyrazine-bridged metal ions, is formed.

PMID- 14703825
TI  - Silica-clay nanocomposites.
AB  - A new class of porous nanocomposite materials have been prepared by reaction of
      alkoxysilanes with alkylammonium-exchanged phyllosilicates (clay minerals), using
      a sol-gel procedure which produces the complete delamination of these layered
      solids.

PMID- 14703824
TI  - Chemical properties of polyamines with relevance to the biomineralization of
      silica.
AB  - Polyamines mimicking substances which occur naturally in biosilicas have been
      synthesized and show an accelerating effect on silica condensation, which depends
      on the chemical nature, the architecture (linear or branched), and the degree of
      polymerization.

PMID- 14703826
TI  - Colloidal stable silica encapsulated nano-magnetic composite as a novel bio
      catalyst carrier.
AB  - A colloidal stable silica-encapsulated magnetic nano-composite of a controlled
      dimension is, for the first time, employed to carry beta-lactamase via chemical
      linkage on the silica overlayer: activity study reflects that this new type of
      immobilisation allows site (enzyme) isolation, accessibility as good as free
      enzyme and recovery & reusability upon application of magnetic separation.

PMID- 14703827
TI  - Unusual enhancement of H2 evolution by Ru on TaON photocatalyst under visible
      light irradiation.
AB  - H2 evolution on TaON photocatalyst under visible light irradiation (420 nm < or =
      lambda < or = 500 nm) in an aqueous methanol solution is found to be remarkably
      enhanced by adding Ru as a noble-metal co-catalyst.

PMID- 14703828
TI  - A ferrocene based palladacyclic precatalyst for the Suzuki cross-coupling of aryl
      chlorides.
AB  - Addition of palladium acetate to 2-(dicyclohexylphosphino)-phenylferrocene gave
      palladacycle 16 that is a very effective precatalyst for the Suzuki cross
      coupling of aryl chlorides at room temperature (1 mol% 16) or 60 degrees C (> or
      = 0.01 mol% 16).

PMID- 14703830
TI  - Electrochemical potential tuned solar water splitting.
AB  - As a fundamental step towards a clean, renewable source of H2, a novel physical
      chemical process within molten NaOH in which an external single, small bad gap
      photosentizer, such as Si, can drive the energetics of water cleavage is
      demonstrated, and is accomplished by tuning (decreasing) the water splitting
      electrochemical potential, EH2O, rather than tuning the photosensitizer band gap;
      this diminished potential is due to (i) a thermodynamic temperature induced
      decrease of EH2O with increasing temperature, and (ii) a partial recombination of
      the cleavage products.

PMID- 14703829
TI  - Pressure-induced formation of a solvate of paracetamol.
AB  - Recrystallisation of paracetamol from a solution in methanol at a pressure of
      0.62 GPa gives a new 1:1 solvate that has been characterised by single crystal X
      ray diffraction.

PMID- 14703831
TI  - Flexible dye sensitised nanocrystalline semiconductor solar cells.
AB  - We report here flexible solid-state solar cells based upon dye-sensitised
      nanocrystalline Al2O3 coated TiO2 films and an I2/NaI doped solid-state polymer
      electrolyte. Such devices show remarkably high solar-light to electrical energy
      conversion efficiencies of approximately 5.3% under 10 mW cm-2 AM1.5
      illumination.

PMID- 14703832
TI  - Ultrafast dynamics of Cu(I)-phenanthrolines in dichloromethane.
AB  - Transient absorption spectrometry of Cu(I)-phenanthrolines in CH2Cl2 reveals
      ligand-independent dynamic processes lasting 15 ps, which are associated with the
      peculiar structural rearrangements occurring for this class of compounds upon
      photoexcitation.

PMID- 14703833
TI  - Structure and electronic properties of an asymmetric thiolate-bridged binuclear
      complex: a model for the active site of acetyl CoA synthase.
AB  - The asymmetric binuclear complex [(dppe)Ni(mu-'S, S')Ni(L)](PF6)2 [L = (N, N'
      diethyl-3,7-diazanonane-1,9-dithiolato)2-] shows a reversible one-electron
      reduction to afford a mixed-valent Ni(II) x Ni(I) species; the reduced complex
      has been characterised by EPR spectroscopy and mimics the redox active Nip site
      in the active A-cluster of acetyl coenzyme A synthase.

PMID- 14703834
TI  - Probe beam deflection study of ion exchange in self-assembled redox
      polyelectrolyte thin films.
AB  - Probe beam deflection during chronoamperometric oxidation-reduction of osmium
      complex in layer-by-layer self-assembled redox active polyelectrolyte multilayers
      has shown that the nature of the charge in the topmost layer determines the ion
      flux that balances the redox charge.

PMID- 14703836
TI  - Living cationic ring-opening polymerization by water-stable initiator: synthesis
      of a well-defined optically active polythiourethane.
AB  - Living cationic ring-opening polymerization under air and water was achieved
      using a well-defined water-resistant cationic initiator in dichloromethane
      without purification at ambient temperature.

PMID- 14703835
TI  - Significant and differential acceleration of dephosphorylation of the
      insecticides, paraoxon and parathion, caused by alkali metal ethoxides.
AB  - In the reaction of paraoxon with alkali metal ethoxides, ion-paired EtO-M+
      species are more reactive than the dissociated EtO- with the reactivity order EtO
      Li+ EtO-Na+ > EtO-K+ > EtO-, while in the reaction of parathion, the reactivity
      follows the order EtO-K+ > EtO- > EtO-Na+ > EtO-Li+.

PMID- 14703837
TI  - A facile synthesis of novel cyclodextrin derivatives incorporating one beta-(1,4)
      glucosidic bond and their unique inclusion ability.
AB  - Novel cyclodextrin derivatives incorporating one (1,4)-glucosidic bond are easily
      synthesized in three steps from permethylated alpha- and beta-cyclodextrins, and
      such host molecules show inclusion selectivity for sodium m-nitrobenzoate over
      the corresponding p-isomer, in contrast to the cases of the parent permethylated
      alpha- and beta-cyclodextrins.

PMID- 14703838
TI  - Novel electrocatalytic activity in layered Ni-Cu nanowire arrays.
AB  - By using template synthesis method, well-defined composite Ni-Cu nanowire
      electrode arrays (CNNEAs) were prepared. Homogeneous nanoparticles of Ni in
      CNNEAs show extraordinary high catalytic activity, which was discussed in terms
      of the size effect of Ni nanoparticles.

PMID- 14703839
TI  - Continuous biphasic catalysis: palladium catalyzed cross coupling reactions.
AB  - The immobilisation of polymer tagged catalysts in a stationary solvent in a
      reactor and the flow of reactants dissolved in another immiscible solvent through
      it, allows the conversion of a continuous feed of reactants into a product
      stream, as exemplified by the Sonogashira coupling of aryl halides and
      acetylenes.

PMID- 14703840
TI  - A fluorescence nanosensor for Cu2+ on silica particles.
AB  - A fluorescence nanosensor for Cu2+ ions has been obtained by surface
      functionalization of silica particles with trialkoxysilane derivatized ligand and
      fluorescent dye.

PMID- 14703841
TI  - A new model of crystal packing.
AB  - A new, conceptually simple model of crystal packing is proposed which uses
      "packing patterns" to describe unit cells in terms of molecular building blocks.

PMID- 14703842
TI  - First observation of highly efficient dehydrogenation of methanol to anhydrous
      formaldehyde over novel Ag-SiO2-MgO-Al2O3 catalyst.
AB  - Novel Ag-SiO2-MgO-Al2O3 catalyst prepared by sol-gel method showed extremely high
      activity and selectivity (both equal to 100%) in the direct dehydrogenation of
      methanol to anhydrous formaldehyde.

PMID- 14703844
TI  - Facile fabrication of 2-dimensional arrays of sub-10 nm single crystalline Si
      nanopillars using nanoparticle masks.
AB  - A simple procedure for the fabrication of sub-10 nm scale Si nanopillars in a 2-D
      array using reactive ion etching with 8 nm Co nanoparticles as etch masks is
      demonstrated. The obtained Si nanopillars are single crystalline tapered pillar
      structures of 5 nm (top) x 8 nm (bottom) with a density of approximately 4 x
      10(10) pillars cm(-2) on the substrate, similar to the density of Co
      nanoparticles distributed before the ion etching process. The uniform spatial
      distribution of the Si nanopillars can also be patterned into desired positions.
      Our fabrication method is straightforward and requires mild process conditions,
      which can be extended to patterned 2-D arrays of various Si nanostructures.

PMID- 14703843
TI  - Hydrogen-ion driven molecular motions in Cu2+-complexes of a ditopic
      phenanthrolinophane ligand.
AB  - One of the first kinetic evaluations of a metal ion interchange between the two
      coordination sites of a ditopic macrocycle is presented.

PMID- 14703845
TI  - Highly-efficient metal-free organic dyes for dye-sensitized solar cells.
AB  - A solar-to-electric conversion efficiency of 6.1% is achieved with this new dye,
      compared to 6.3% for N3 dye under the same experimental conditions. Although
      these indoline dyes are slightly less efficient than N3 dye, the cost of indoline
      dye is much less than for N3 due to ease of preparation. Furthermore, indoline
      dyes are shown to be highly stable to photoredox processes by cyclic
      voltammogram.

PMID- 14703846
TI  - Functional analysis of the biomimetic silica precipitating activity of the R5
      peptide from Cylindrotheca fusiformis.
AB  - A synthetic site-directed mutagenesis study of the non post-translationally
      modified silica precipitating R5 peptide reveals that the RRIL motif is critical
      in the formation of active silica precipitating assemblies.

PMID- 14703847
TI  - Crown-ether functionalised second coordination sphere palladium catalysts by
      molecular imprinting.
AB  - Functionalisation of the second coordination sphere of a molecularly imprinted Pd
      complex was achieved by localising within the polymeric cavity a crown-ether
      receptor capable of altering the catalytic activity of the reactive site.

PMID- 14703848
TI  - A diatropic ring current in a fluorofullerene trannulene.
AB  - Ipsocentric current-density maps for a fluorofullerene derivative, C60F15H3,
      modelling the addition pattern of the experimentally characterised
      C60F15[CBr(CO2Et)2]3 which contains an [18]trans-annulene system, reveal a
      diamagnetic ring current dominated by the contribution of the four HOMO
      electrons, as in a classical (4n + 2) aromatic annulene.

PMID- 14703849
TI  - Domino 'Staudinger-aza-Wittig-1,5-phosphonium-rearrangement-fragmentation'
      reactions of 1-azido-2-hydroxy-4,6-dioxohexanes.
AB  - The domino 'Staudinger-aza-Wittig-1,5-phosphonium-rearrangement-fragmentation'
      reaction of 1-azido-2-hydroxy-4,6-dioxohexanes allows a convenient synthesis of
      functionalized 1-acetamido-2-alkylidenecyclopentanes.

PMID- 14703850
TI  - Synthesis and characterization of luminescent osmium(II) carbonyl complexes based
      on chelating dibenzoylmethanate and halide ligands.
AB  - Octahedral Os(II) complexes 1-5 with formula [Os(CO)3X(dbm)] are prepared through
      utilization of both solid-state pyrolysis and ligand exchange reactions. These
      complexes exhibit prominent 3pi-pi* phosphorescence with unusually long lifetimes
      (29-64 micros) and high quantum yields (0.08-0.13).

PMID- 14703851
TI  - Lanthanide complexes derived from (R)-1,1'-binaphthyl-2,2'-bis(neopentylamine)-
      (Li(THF)4)(Ln[(R)-C20H12N2(C10H22)]2) (Ln = Sm, Yb)--novel catalysts for
      enantioselective intramolecular hydroamination.
AB  - The complexes (Li(THF)4)(Ln[(R)-C20H12N2(C10H22)]2) (Ln = Sm, Yb) have been
      synthesized, fully characterized and found to be efficient and enantioselective
      catalysts for intramolecular hydroamination of 1-(aminomethyl)-1
      allylcyclohexane.

PMID- 14703852
TI  - Synthesis and field emission of carbon nanotubular fibers doped with high
      nitrogen content.
AB  - Nitrogen-doped carbon nanotubular fibers with a very high nitrogen concentration
      (approximately 20 at.%) were synthesized through the aerosol-assisted
      decomposition of dimethylformamide in the presence of catalyst. The synthesized
      fibers process a novel "pearl necklace-like" morphology and exhibit an excellent
      field emission performance.

PMID- 14703853
TI  - A novel diastereoselective route to alpha-hydroxyalkyl dihydropyrans using an
      hetero Diels-Alder/allylboration sequence.
AB  - The development of a new strategy for the synthesis of alpha-hydroxyalkyl
      dihydropyrans is reported. This approach is based on a tandem hetero[4 +
      2]/allylboration reaction.

PMID- 14703854
TI  - Characterisation of fresh and aged terpenic resins by micro-FTIR and GC-MS
      analyses of varnishes in XVI-XVII centuries paintings.
AB  - Resinous materials, generally added to drying oils, were often employed as final
      protective films in paintings, both in tempera and oil techniques. Most of the
      resins used in fine arts come from exudates of plants. Natural resins are mainly
      composed by terpenoids. Among these resins, dammar, rosin, mastic, elemi gum,
      Venice turpentine were frequently employed in easel paintings. The aim of this
      work is the identification of natural resins in samples collected from works of
      art. In this paper we propose to use micro-FTIR spectrometry as a preliminary and
      non destructive technique to detect the presence of resinous materials in
      microsamples collected from paintings, followed by GC-MS analyses to obtain a
      precise identification of the resin. To reach this aim commercial resins,
      employed as standard, were analysed previously by micro-FTIR spectrometry and
      then analysed by GC-MS chromatography, searching characteristic chemical
      compounds used as "markers" of resins. The results obtained on standards allowed
      us to successfully analyse samples collected from two works of art: the "Portrait
      of a Young Gentleman", by Lorenzo Lotto (XVI century), and the "Madonna with the
      Infant Jesus and Saints": by Carlo Maratta (XVII secolo).

PMID- 14703855
TI  - The Assisi Chartula by the hand of Saint Francis: non-destructive
      characterization by spectroscopic spectrometric and optical methods.
AB  - Just two examples of writings by the hand of S. Francesco are known to exist: a
      letter to Brother Leone, kept in the archives of Spoleto cathedral and the
      Chartula, displayed in the Hall of Reliquaries at Assisi's Sacro Convento. For
      the first time in its history the Chartula has undergone a series of non
      destructive analyses, with the object of establishing its current state of
      conservation and the types of inks used in its making. A new display case has
      been designed and built for the improved conservation of this precious document.
      The new housing substitutes an ancient case, which was located inside the
      original reliquary.

PMID- 14703856
TI  - The stucco work of Giacomo Serpotta and the Serpotta School. Constitutive
      materials, degradation and decay.
AB  - Giacomo Serpotta (1656-1732) was the major figure of a school of stucco work
      which was growing and developing in Palermo in the course of several decades
      towards the end of the 17th century. This paper presents some preliminary results
      of a wide and systematic comparative study, aimed at investigation of the
      compositional and textural characteristics of the stucco, and of the techniques
      of the modeling and finishing of its surfaces, by means both of measurements of
      physico-chemical properties of the materials and of their mineralogical and
      petrographic characterization. The opportunity for such a study was made
      available by the launching of the "Progetto Serpotta" by the Soprintendenza dei
      Beni Ambientali e Culturali di Palermo. This project is aimed at the restoration
      and conservation of most of the Serpotta school stucco works. The project offers
      a unique opportunity to extract samplings from the entire cycle of works prior to
      restoration. Moreover, the study of the stucco's material composition serves as
      an aid in better understanding the nature and the causes of degradation and
      decay, which in many cases have seriously damaged the works.

PMID- 14703857
TI  - Correct use of the contact angle in the evaluation of the protective action
      induced from polymer coating on the stone.
AB  - The control of the protective efficacy obtained on the stone by treatments with
      polymers is commonly performed through the measure of the static contact angle as
      it is described by the norm UNI 10921. However this approach does not allow an
      easy interpretation of the results, because of the porosity and of the
      heterogeneity of the stone surface, which represent an obstacle to the analysis.
      Moreover the commonest interpretation of this technique can often bring to
      important errors. The measure of the static contact angle substantially
      corresponds to the measure of the so-called "advancing" contact angle and it
      allows only to verify if on the surface a hydrophobic material is present;
      unfortunately it cannot determine if the stone is effectively protected. Vice
      versa, both, the measure of the "true" equilibrium contact angle obtained through
      a new technique called VIECA, and the measure of the receding contact angle give
      more coherent parameters which better correlate with the data of absorption of
      water by capillarity. The equilibrium contact angle corresponds to an "average"
      description of the surface, the receding angle corresponds, by excess, to the
      condition of maximum penetration of the liquid by capillarity. From the knowledge
      of the equilibrium angle of the protective polymer and from the measure of the
      advancing and receding angles of the protected stone, it is certainly possible to
      determine what is the minimum polymer quantity to obtain an almost homogeneous
      stone protection.

PMID- 14703858
TI  - Fungal colonization on stoneworks. Interaction fungi-powdered stone samples.
AB  - The microbial activity plays an important role in the biodegradative processes
      implied in stonework decay. In natural environments it is not possible to
      separate the damage produced by microorganisms from damage caused by physical and
      chemical agents. In vitro assays carried out with microbes isolated from
      weathered stones are required in order to understand the biological mechanisms
      involved in stone deterioration. We have described, as commented in the text, how
      fungal colonization observed on scaglia may be the result of the fine grain size
      of rock, whereas inhibition of growth on marble may depend on the surface
      characteristics of calcite grains after grinding. The extent of microbial growth
      clearly depends on the quantity of cations released in solution. However, fungal
      growth may, in turn, induce a decrease in pH, thus promoting mineral chemical
      attack. These observation points to selective action of fungal species in
      promoting weathering well evidenced by the presence of different extents of
      cations released in suspension from the same sample. Detailed studies are in
      progress in order to go into this question.

PMID- 14703859
TI  - Thermogravimetric and kinetic methods to date wood finds. First results.
AB  - Fresh (larch and fir, in its white and red varieties) and ancient wood samples
      (dating respectively to the 13th, 15th and 17th centuries) were subjected to
      thermogravimetric analysis (TG and DTG). The resulting thermogravimetric data
      were then used to construct archeometric curves for the wood varieties tested. In
      a preliminary approach, it was attempted to correlate the onset temperature of
      the thermogravimetric step corresponding to cellulose decomposition with the age
      (expressed in centuries) of the samples, although the results obtained were
      anything but brilliant. More encouraging results were obtained by examining the
      relationship between wood sample age and the value of the (percent
      cellulose/percent lignin) ratio computed from the thermogravimetric data. Lastly,
      a procedure for processing data obtained from the TG curves was applied to a
      kinetic analysis of the processes that take place when wood samples are subjected
      to a temperature regime with a constant heating rate, obtaining values for the
      activation energy of the TG step corresponding to the decomposition of cellulose.
      Also using these data it was attempted to construct archeometric curves,
      obtaining results that varied quite significantly according to the wood species
      tested.

PMID- 14703860
TI  - Diagnostics and conservation of a gres work by Zauli placed in the Bucci park of
      Faenza.
AB  - Glazed more or less degraded ceramic works, made by the sculpture artist Carlo
      Zauli from Faenza, were studied. One of them, placed outside in the Bucci park,
      showed a lot of fractures, lacunas and biological decay. Therefore, a diagnostic
      study, a preliminary in situ restoration and a monitoring for over two years were
      carried out in order to verify the stability of the work.

PMID- 14703861
TI  - Conservative restoration of the Augustus Arch of Fano: cleaning methodology as
      derived from preparatory analyses and sampling.
AB  - The original appearance of Augustus Arch of Fano was compromised by a diffuse
      distribution of black scales and other deposits. In order to preserve the stone
      surface the restoration intervention operated with different cleaning techniques
      so that it was possible to use every method with a properly and not dangerous
      intensity. In particular it showed the possibility to use laser cleaning to
      destroy the external hard part of black scales, and complete the intervention
      with light chemical cleaning. In the case of Augustus Arch this way resulted
      useful for preserve signs on surface and cleaning every kind of deposits at the
      same time. Every intervention on such an important monument need to obtain at the
      same time the best result for materials conservation and the aim of image
      restore.

PMID- 14703862
TI  - The restoration of the Sangallo bastion in Fano: researches, surveyings, and
      conservation techniques.
AB  - The restoration plan, still in progress, of the Sangallo bastion in Fano, by
      Antonio da Sangallo the Younger, is the result of a deep research to sketch the
      chronographic complexity of the monument. By direct surveys--such as endoscopic
      tests, georadar profiles, chemical analysis in order to monitor the nature and
      the deterioration of the materials--it was possible to develop an "in itinere"
      conservation plan, explaining the obtained results with the historical research.

PMID- 14703863
TI  - Oxidation of phosphorus compounds by Fenton's reagent.
AB  - In the present work a Fenton's treatment for the oxidation of a phosphorous
      compounds mixture, simulating a match manufacturing industry wastewater, were
      studied. Experimental tests were performed on three sample solutions at a
      phosphorus concentration of 250, 500 and 750 mg/l. In each solution an equal
      amount of sodium phosphite and sodium hypophosphite was dissolved. The
      investigation of pH, temperature and reagents ratio on the oxidation rate led to
      the individuation of the optimal process operating conditions. The results show
      that Fenton's reagent provides a powerful conversion to phosphate of the
      phosphorous solution. In particular at pH=3.5 and 20 degrees C a residual
      concentration of non oxidized phosphorus in compliance with the Italian
      regulation limits for industrial wastewater disposal. Tests performed on sample
      solution of 500 mg/l P and 750 mg/l P by adding hydrogen peroxide and bivalent
      iron in three sequential steps led to similar reaction efficiencies to tests
      carried out adding both Fenton's reagents in one step, but with a remarkably
      lower reagents consumption.

PMID- 14703864
TI  - Epoxy-silica hybrids as stone restoration materials.
AB  - Hybrid organic-inorganic systems based on two epoxy-resins, the aromatic DGEBA
      and the aliphatic Eurostac 2101, and the amine ATS were developed for stone
      conservation. Their efficacy, explored through some preliminary tests such as
      water absorption, mercury porosimetry and appearance, was evaluated on two
      selected lithic typologies, Mistretta quartzite (MIS) and Comiso calcarenite
      (COM). The experiments carried out on MIS showed that none of the employed
      mixtures is able to significantly affect its porosimetric properties, while only
      DGEBA/ATS solutions reduce its water absorption, but cause not negligible
      alterations in appearance. The treatment of COM with DGEBA/ATS solutions does not
      alter significantly the porosimetric features while preventing the water
      migration inside the stone. On the contrary EP/ATS mixtures perform better in
      porosimetric terms, while water absorption tests are not promising.

PMID- 14703865
TI  - Air-monitoring of volatile aromatic compounds in the town of Viterbo.
AB  - Results obtained by using Analyst, a long term diffusive sampler, for monitoring
      volatile aromatic compound in the town of Viterbo are presented. Benzene,
      toluene, ethylbenzene and also the three xylene isomers are evaluated during six
      months of measurements. The obtained values and also the ratios of some
      pollutants are reported and discussed.

PMID- 14703866
TI  - C-reactive protein in monitoring and evaluation of effects of therapy of the MMA
      syndrome of sows.
AB  - The elevated concentration of CRP in sows at the early stage of the MMA reflected
      the inflammation in the reproductive tract and in the mammary gland. Monitoring
      the level of CRP during the first days after parturition may be used to diagnose
      early stages of the MMA and to start therapy. In the treated MMA sows the level
      of CRP steadily decreased, and by the end of the experiment it had returned to
      the normal level. In the non-treated MMA sows CRP persisted at a high level and
      at day 10 of the experiment it was 13 times higher than in the treated animals
      and 16 times higher than in controls. Measurements of serum CRP are valuable in
      monitoring the health status of sows after parturition and should be introduced
      as the diagnostic method of the MMA syndrome in sows. The determination of the
      concentration of serum CRP during the first two days after parturition should be
      used for diagnosis of the early stages of MMA syndrome in sows and to start
      therapy when clinical symptoms of MMA are still absent.

PMID- 14703867
TI  - Influence of zearalenone on reproductive system cell proliferation in gilts.
AB  - Zearalenone (ZEA) is a macrocyclic lactone, estrogenic, diet-depending and
      fusaric micotoxin, which is produced on many kinds of cereals and feeds in the
      favourable conditions of humidity and temperature. The structure of ZEA is
      similar to the structure of estrogens and it enables binding to the estrogenic
      receptors. The stimulation of protein synthesis in the cells of the reproductive
      system, which causes intensification of cell proliferation, is one of the effects
      of ZEA actions. Oedema and vulva reddening are the clinical, external signs of
      ZEA intoxication in pigs. The aim of this study was to designate the degree of
      reproductive cell proliferation after low doses of ZEA were applied per os in
      sexually immature gilts with simultaneous monitoring of zearalenone and alpha
      zearalenol levels in peripheral blood. The following were observed in the gilts
      examined fluctuations of zearalenone and alpha-zearalenol levels in blood, which
      were connected with entero-hepatic circulation and also numerous
      histopathological changes in ovarian follicle structure. These changes were
      present in the reproductive system of sexually immature gilts with a big
      contribution of PCNA-positive cells. The studies show that zearalenone
      application in sexually immature gilts caused ovarian follicle atresia and
      apoptoso-like changes in granule cells. Intensified cell proliferation, which was
      expressed with the growth of PCNA index, was observed in uterus and oviduct.

PMID- 14703868
TI  - The presence of Helicobacter-like microorganisms in the gastric mucosa in dogs.
AB  - The aim of this study was the evaluation of the occurrence of Helicobacter-like
      organisms in the gastric mucosa of dogs. The study was performed on samples of
      gastric mucosa obtained during necropsies from 94 dogs euthanasized for various
      reasons. Histopathological examination and also urease test was performed.
      Helicobacter sp. was found in 85.10% of examined dogs. In 36% cases the presence
      of bacteria was accompanied by chronic inflammation of gastric mucosa localized
      mainly in pyloric region. In 97.59% samples positive results of urease test were
      associated with histopathological confirmation of gastric Helicobacter-like
      organisms.

PMID- 14703869
TI  - The localization and connections of suboviductal lymphatic vessels in the bovine
      uterine broad ligament.
AB  - The distribution of oviductal lymphatic vessels in the bovine mesosalpinx and
      bursa ovarica, and their communications with other lymphatics in the uterine
      broad ligament were examined after exposition of all lymphatic pathways with
      varicoloured microfil and/or ink-gelatin mixture. However, filling of the lumen
      of the oviductal infundibulum lymphatics was difficult or impossible because of
      its slender walls. Lymphatics of the isthmus and ampulla with short precollectors
      formed branches 1.5-2.0 cm long on both sides: dorsal and ventral of the uterine
      broad ligament. Collectors with slender and long lymphangions, visible after
      filling their lumen, encircled the alymphatic area in the parainfundibullar
      mesosalpinx. The greatest number of lymphatic branches, which originated from the
      paraisthmal part of the oviductal ampulla were observed in the subovarian area.
      The characteristic feature was their immediate proximity with uterine and
      oviductal arterial vessels. Subsequent studies have provided convincing evidence
      that there are direct connections of lymphatics leaving the oviduct and ovarian
      sac with lymphatics emerging from the uterus and ovary (after bilateral filling
      of lymphatics pathways in the whole broad liagment of the uterus). The performed
      investigations showed particularly characteristic feature in the cow--mixing
      lymph leaving various reproductive organs in the area of the right and left
      ligament--before two long collector branches reach the nearest lymphatic node/-s.

PMID- 14703870
TI  - Relationships among ecology, demography and diseases of European bison (Bison
      bonasus).
AB  - The bison population in the Bialowieza Forest in Poland has now grown to
      approximately 300, while the herds in the Belarusian part of the forest total
      about 240 bison. The first signs of a health problem in these herds appeared in
      1980, when two cases of balanoposthitis were detected in two bulls (2 and 5 years
      of age). Since 1980 research has been conducted to explain the cause of diseases,
      particularly balanoposthitis, and to monitor the health of bison in Bialowieza
      Forest. A total number of 614 bison (294 male and 320 female) of different ages
      was eliminated between 1980 and 2000. Not all the culled bison were examined
      (postmortem analysis, histopathological, bacteriological, virological and
      toxicological examinations, serological tests, molecular research). Based on the
      increase in numbers, reproduction in this population for the past 21 years is
      generally considered successful. Among 182 male bison eliminated during 1990
      2000, only 85, or 47%, of the animals had balanoposthitis. Thus, the percentage
      of balanoposthitis cases went from 100% during the 1980s down to 47% in the past
      decade. It appears that the culling process has been a major factor leading to
      this decrease. It can be assumed that a set of factors is involved in the
      appearance of the disease (Corynebacterium spp., Bacillus sp., Pseudomonas
      aeruginosa, Escherichia coli, Ureoplasma spp, Fusobacterium necrophorum,
      Streptoccocus spp., Staphyloccocus spp.) while opportunistic infections including
      nematodes (Onchocerca spp.) are responsible for the occurrence of secondary
      lesions.

PMID- 14703871
TI  - Survival of Enterococcus hirae in ripened cheese subjected to ultra high
      pressure.
AB  - The samples of a sliced, hard cheese were placed in commercially used polyamide
      polyethylene bags, inoculated with E. hirae and sealed under vacuum. The samples
      were exposed to high hydrostatic pressure of 300, 400 and 500 MPa for 5, 10 and
      15 min. The number of surviving E. hirae and Aerobic Plate Counts (APC) were
      determined. The bacterial counts were transformed to logarithms and D-values
      (time required for decimal reduction of E. hirae at given pressure) were
      calculated using linear regression method. It was found that numbers of E. hirae
      decreased with the increase of pressure and prolongation of treatment time. D
      values amounted to: D300MPa - 33.67 min, D400MPa - 17.83 min and D500MPa - 16.03
      min. The obtained results indicate that E. hirae is one of the most resistant
      vegetative bacteria to ultra high pressure treatment.

PMID- 14703872
TI  - Ingestion capacity of PMN cells in peripheral blood of rabbits experimentally
      infected with VHD (viral haemorrhagic disease) virus strains originating from
      various biotopes.
AB  - The study presents results of investigations on ingestion capacity in rabbits
      experimentally infected with two French strains (Fr-1 and Fr-2) and four Polish
      strains (KGM, SGM, MAL, Kr-1) of VHD virus. The results proved that the strains
      studied exhibited distinct reactivity even if the VHD virus is thought to be
      uniform in the biological respect.

PMID- 14703873
TI  - Preliminary study of the influence of plasma proteins on immunological and
      production parameters in pigs.
AB  - The health and productivity of pigs is important to farmers worldwide. One
      potential method of improving animal health is by providing functional proteins
      in the diet, for example spray-dried animal plasma (SDAP). These proteins,
      particularly plasma IgG, can improve health in many species, including humans. By
      unspecific activation of the immune system, SDAP can reduce morbidity and
      mortality as well as improve growth and efficiency what results in reduced costs
      of production. In this study, the influence of SDAP on expression of T-lymphocyte
      markers and production parameters in weaned pigs was evaluated. The results
      showed a significant increase in the percentage of T-lymphocytes, especially the
      CD8+ subpopulation, as well as a positive effect on body weight gain.

PMID- 14703874
TI  - Pharmacological and toxicological aspects of combination of beta-lactam and
      aminoglycoside antibiotic, prednisolone and procaine hydrochloride on the example
      of Vetramycin.
AB  - Vetramycin is an injectable veterinary compound for animal use only. In
      veterinary medicine, it has been used for a long time as a bactericidal beta
      lactam and aminglycoside antibiotics combination, extending the bactericidal
      spectrum of these substances. This compound, in addition to bactericidal procaine
      penicillin and dihydrostreptomycin (DHS), contains also prednisolone acetate and
      procaine hydrochloride, two biologically active substances. Prednisolone, a
      glucocorticoide, has an antiinflammatory, antiallergic, antiitchical and
      analgesic effect. Procaine hydrochloride, in turn, has a local anaesthetic effect
      and attenuates pain caused by irritable properties of antibiotics at the
      injection sites. The average dosage of, respectively, procaine benzylpenicillin
      (I.U./kg(-1) b.w.), DHS (microg/kg(-1) b.w.), prednisolone acetate (microg/kg(-1)
      b.w.) and procaine hydrochloride (mg/kg(-1) b.w.) in horses, cattle, pigs is 6000
      15000, 10-11, 0.24-0.6 and 1.2-3.0; s.i.d., in sheep, foals, calves, piglets is
      20000-40000, 10, 0.8-1.6 and 4-8; s.i.d., in dogs and cats is 30000-200000, 10,
      0.8-1.6 and 4-8; s.i.d.. Intramammary injection dose (Vetramycin antimastitis
      ointment in syringe) in cows is 1000000 I.U. of procaine benzylpenicillin +
      1000000 I.U. of dihydrostreptycin sulphate per quarter of udder, s.i.d., during 3
      successive days.

PMID- 14703875
TI  - Troponin--a new marker in the diagnostics of muscle diseases in animals.
AB  - The dysfunction of muscles, especially that of the cardiac muscle, is one of the
      most dangerous for the life pathological states. The determination of biochemical
      indexes such as AST, ALT, CK, LDH, mioglobin, etc., which has been used so far in
      animals is not a sufficient diagnostic method. Therefore, new markers, levels of
      which could reflect the state of a patient more precisely, have been sought.
      Troponin, a protein found in skeletal and cardiac muscles only, has been
      considered a reliable index of myocardial ischemia in animals, especially in
      dogs. Its diagnostic properties have appeared to be a valuable complementation of
      the other diagnostic methods and thus could have gained a lot of veterinary
      practitioners interest.

PMID- 14703876
TI  - Role of the antioxidants in the protection against oxidative stress in cattle-
      nonenzymatic mechanisms (Part 2).
AB  - Antioxidative status consists of two mechanisms: nonenzymatic and enzymatic
      mechanisms. Nonenzymatic mechanisms are composed of antioxidants, scavengers of
      free radicals, transition metal ions, sequester transition metal ions, albumins,
      ceruloplasmin, and metallothioneins. On the other hand, enzymatic mechanisms are
      composed of superoxide dismutase (SOD), peroxidase, catalase and reductase. In
      cattle, characteristics of these mechanisms depend on the nutritional status of
      anti-oxidant minerals, especially copper, zinc, iron, selenium, silicon, and
      manganese. The nutritional status of the cattle in different regions of the world
      and in Poland is often characterised by the lack of these minerals; therefore,
      there is a great potential for changes in the activity of defence mechanisms
      against free radicals.

PMID- 14703877
TI  - Unsolved problems in the management of patients with gastro-oesophageal reflux
      disease.
AB  - Gastro-oesophageal reflux disease is a common problem that brings large numbers
      of patients to physicians every day. It lowers the quality of life of affected
      individuals and exposes them to potentially dangerous complications. An
      increasing awareness exists among patients, doctors and authorities about the
      relevance of this pathological condition. Despite an improved understanding of
      many aspects of gastro-oesophageal reflux disease, clinical management of several
      cases is still unsatisfactory. Atypical cases with extra-oesophageal
      manifestations often defy diagnosis. Even typical symptoms are often
      misunderstood and considered to be part of the poorly defined area of dyspepsia
      by both patients and doctors. As a consequence, management remains uncertain for
      too many cases. If correctly diagnosed, gastro-oesophageal reflux disease can be
      efficaciously treated with proton pump inhibitors (PPIs). Although standard doses
      of PPIs can heal mucosal lesions and provide symptom relief in the vast majority
      of oesophagitis patients, non-oesophagitis symptomatic individuals and those with
      extra-oesophageal manifestations may fail to respond to similar regimens.
      Antireflux surgery is a possible alternative to PPI therapy, but it is hampered
      by complications in a substantial percentage of cases and by sporadic casualties
      even when performed by experienced surgeons. The high prevalence of gastro
      oesophageal reflux disease in the general population and the relatively high
      management costs should prompt any doctor to seek the best possible therapeutic
      approach.

PMID- 14703878
TI  - The burdens imposed by Crohn's disease: messages for clinicians?

PMID- 14703879
TI  - Endoscopic hydrostatic dilatation of intestinal strictures in Crohn' s disease.

PMID- 14703880
TI  - Burden of illness of Crohn's disease in Spain.
AB  - OBJECTIVE: To evaluate the burden of Crohn's disease in Spain. DESIGN:
      Observational, cross-sectional study of patients affected with Crohn's disease
      who were attended to in hospitals in Spain. METHODS: Three structured
      questionnaires were used: one completed by the gastroenterologists to obtain
      demographic, clinical and disease activity data; a phone interview to obtain
      epidemiological and drug utilisation data; and the Spanish version of the Short
      Form Health Survey (SF-36). RESULTS: The annual cost per patient was estimated at
      Euro 6808-Euro 2104 from direct medical costs and Euro 4704 from indirect costs.
      Approximate effect sizes for health-related quality of life were as follows: 0.8
      for general health, social function, role functioning--physical and vitality; 0.5
      for role functioning--emotional, body pain and mental health; and 0.2 for
      physical function. CONCLUSION: Crohn's disease causes a significant decrease in
      health-related quality of life for patients and a considerable economic cost to
      society, mainly due to hospitalisations and loss of productivity. This burden
      indicates the importance of health programmes and interventions in reducing the
      heavy impact of the disease on both patients and society.

PMID- 14703881
TI  - Diagnostic role and clinical correlates of anti-Saccharomyces cerevisiae
      antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (p-ANCA) in Italian
      patients with inflammatory bowel diseases.
AB  - BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti
      neutrophil cytoplasmic antibodies (p-ANCA) are serological markers associated,
      respectively, with Crohn's disease and ulcerative colitis, whose clinical
      significance and possible diagnostic role are still poorly defined. AIMS: (a) To
      evaluate the sensitivity, specificity and predictive values of isolated and
      combined ASCA and p-ANCA assays in a large cohort of Italian patients with
      inflammatory bowel disease (IBD) and (b) to assess whether their presence is
      associated with particular clinical features of the disease. PATIENTS AND
      METHODS: Hundred and forty-six IBD patients (93 with Crohn's disease and 53 with
      ulcerative colitis) and 54 control patients were enrolled in the study. ASCA (IgA
      and IgG) and p-ANCA were determined by means of enzyme-linked immunosorbent assay
      and indirect immunofluorescence, respectively. RESULTS: The specificities were
      excellent for both tests (ASCA in Crohn's disease, 98.1% both for IgA and IgG,
      and p-ANCA in ulcerative colitis, 92.5%); however, the sensitivities of both
      tests were low (59.1% for ASCA IgA, 44.1% for ASCA IgG, 39.6% for p-ANCA). ASCA
      specificity and positive predictive value reached 100% when positivity for both
      IgA and IgG was present. No significant association was found between the
      presence of a specific serological marker and patients' clinical features.
      CONCLUSIONS: This study confirms the low prevalence of p-ANCA observed in
      ulcerative colitis patients from the Mediterranean area. The low sensitivity of
      ASCA and p-ANCA, despite their rather high specificity, renders them of little
      value in the screening of the general population, where the prevalence of IBD is
      low. However, in our series, a double positivity for ASCA IgA and IgG identifies
      with certainty the presence of Crohn's disease.

PMID- 14703882
TI  - Symptom-based approach to colorectal cancer: survey of primary care physicians in
      Italy.
AB  - BACKGROUND: Colorectal cancer is a frequent cause of mortality in Western
      countries, including Italy, where a definite screening policy has not yet been
      adopted. It is likely that most patients with colorectal cancer refer, first of
      all, to their primary care physician at onset of symptoms. AIM: To perform a
      survey on the approach, of primary care physicians, to patients with symptoms
      suggesting the presence of colorectal cancer. METHODS: A total of 280 consecutive
      symptomatic patients without previous diagnosis of organic colon disease or
      recent colon investigation in whom, after consulting, 159 primary care physicians
      in Lazio (Italy) prescribed colonoscopy or double-contrast barium enema. RESULTS:
      Most frequent presenting symptoms were lower abdominal pain (79.6%), bloating
      (59.6%), constipation (47.8%), diarrhoea (30.3%), iron deficiency anaemia
      (24.6%), change in bowel habits (20.3%) and weight loss (15%). Colonoscopy and
      barium enema were equally advised by physicians to rule out the presence of
      cancer (56% versus 44%, P = ns). Cancer was found in 14.6% of patients. Age > 50
      years and iron deficiency anaemia were the only independent variables associated
      with colorectal cancer (Odds ratios 9.0 and 8.8 at multivariate analysis,
      respectively). CONCLUSION: The symptom-based selection criteria used by primary
      care physicians have been shown to be scarcely effective. Colonic investigation
      should be requested, irrespective to the symptoms, in patients aged > 50 years
      with iron deficiency anaemia.

PMID- 14703883
TI  - Sphincter-saving surgery in patients with rectal cancer treated by radiotherapy
      and transanal endoscopic microsurgery: 10 years' experience.
AB  - BACKGROUND/AIMS: Transanal endoscopic microsurgery (TEM) is a technique which
      allows minimally invasive full-thickness local excision of rectal tumours with
      perirectal fat dissection. METHODS: Our study examined a group of 137 selected
      patients with rectal cancer treated by TEM excision combined with preoperative
      radiotherapy. The definitive histology was as follows: 37 patients with pT1 stage
      rectal cancer (27%), 59 with pT2 (43%) and 23 with pT3 (17%). In 18 (13%)
      patients who underwent a full dose of radiotherapy and TEM, the pathologist did
      not find cancer cells in the specimen (pT0). RESULTS: Eleven (8%) patients
      developed minor complications, whereas three (2%) developed major complications.
      The perioperative mortality was nil. At the mean follow-up of 46 months (range 6
      115 months), we observed seven (5%) local recurrences. Of those, three patients
      died from systemic spread of the disease at follow-up. The disease-free survival
      rate in T0 and T1 patients was 100%. The disease-free survival rates in T2 and T3
      patients were 81 and 59%, respectively, at a mean follow-up of 46 months.
      CONCLUSIONS: The application of preoperative radiotherapy and TEM in the
      treatment of rectal tumours appears feasible, safe and effective in the present
      study, with optimal preservation of anal sphincter function.

PMID- 14703884
TI  - Predicting bone mineral density of postmenopausal healthy and cirrhotic Italian
      women using anthropometric variables.
AB  - BACKGROUND: Chronic liver diseases, including cirrhosis of the liver, have been
      shown to cause bone osteometabolic disease giving rise to osteoporosis and
      osteomalacia. AIMS: To develop mathematical prediction equations for the lumbar
      spine, pelvis and total bone mineral density based on the osteoporosis risk
      factors age and body mass index in cirrhotic and healthy postmenopausal women.
      PATIENTS: Twenty-seven postmenopausal women with liver cirrhosis (Child-Pugh
      class A) and well-preserved liver function (Late postmenopausal cirrhotic), 27
      women matched for age and body mass index (Late postmenopausal healthy) and 27
      younger women matched only for body mass index (Early postmenopausal healthy).
      METHODS: Segmental and total fat mass, lean body mass and bone mineral density
      were measured for all participant women using dual X-ray absorptiometry. RESULTS:
      Segmental and total fat mass and bone mineral density were significantly lower
      for Late postmenopausal cirrhotic women as compared with Late and Early
      postmenopausal healthy women. Segmental and total lean body mass were comparable
      among the three study groups. CONCLUSIONS: The mathematical equations based on
      the variables age and body mass index were capable of predicting lumbar-spine
      bone mineral density, pelvis bone mineral density and total bone mineral density
      for the three groups of postmenopausal women with the lowest standard error of
      estimation and root mean square residuals of predictions for equations describing
      the Late postmenopausal healthy group.

PMID- 14703885
TI  - Liver, pancreas and biliary tract enhanced lipoperoxidation products in pure
      pancreatic juice: evidence for organ-specific oxidative stress in chronic
      pancreatitis.
AB  - BACKGROUND: Oxygen-free radicalscan play a role in the development of chronic
      pancreatitis, altering the redox state with damage of cell constituents and
      decrease in antioxidant defences. AIMS: To measure levels of lipoperoxidation
      products, conjugated dienes and lipid hydroperoxides, in pure pancreatic juice
      and serum of chronic pancreatitis patients and compare them to that in controls.
      To investigate a possible correlation with serum indexes of pancreatic
      inflammation (amylase and lipase). PATIENTS: Pancreatic juice was collected
      during ERCP, after secretin stimulation, in 20 patients with chronic pancreatitis
      and 11 controls with biliary diseases. METHODS: Lipid hydroperoxide levels were
      determined with FOX2 method and measured as absorbance at 560 nm. Conjugated
      diene levels were measured using second-derivative spectroscopy. RESULTS: No
      substantial difference was present in serum levels of lipid hydroperoxides,
      conjugated dienes (in both isomeric forms) and isomer-ratio values between those
      of patients with chronic pancreatitis and controls. In pancreatic juice, there
      was a significant increase in lipid hydroperoxides and conjugated dienes levels
      (especially trans-trans isomers) in chronic pancreatitis patients compared with
      controls, with a decrease in cis-trans isomers and a significant difference in
      isomer-ratio values. CONCLUSIONS: Increased levels of lipid hydroperoxides and
      conjugated dienes in the pancreatic juice of chronic pancreatitis patients is
      indicative of an enhanced lipoperoxidation and antioxidants consumption in
      pancreatic tissue, confirmed by the decreased isomer-ratio values as an indirect
      index of decreased antioxidant capacity. The lack of significant difference in
      conjugated diene and lipid hydroperoxide levels in the serum of chronic
      pancreatitis patients versus that of controls suggests an oxidative stress
      limited to pancreatic tissue and indicative of an organ-specific pathology,
      confirmed by the parallel behaviour of oxidative parameters (lipid hydroperoxides
      and conjugated dienes) and indexes of pancreatic inflammation (amylase and
      lipase).

PMID- 14703886
TI  - Long-term outcome of endoscopic pneumatic dilatation in Crohn's disease.
AB  - BACKGROUND: To avoid multiple surgeries in stenosing Crohn's disease, pneumatic
      endoscopic dilatation has been introduced. The present study evaluated the long
      term clinical outcome in Crohn's disease patients after endoscopic dilatation for
      ileal or neoileal strictures. PATIENTS AND METHODS: All Crohn's disease patients
      who underwent pneumatic dilatation of ileal or ileo-colonic strictures between
      January 1988 and December 2001 were invited to return for a clinical check-up in
      June 2002. Clinical, endoscopic and radiological reports were reviewed.
      Symptomatic relief from sub-occlusive symptoms without requiring surgery was
      considered as a positive outcome, whereas the requirement of surgery was regarded
      as an unfavourable outcome. Possible predictors of favourable outcome were
      analysed. RESULTS: Endoscopic dilatation was technically successful in 34/43
      (79%) Crohn's disease patients, with a mean number of dilatations per patient of
      3 +/- 3.13. During a mean follow-up of 63.7 +/- 44.6 months, a positive long-term
      outcome was observed in 18 (52.9%) patients, whereas surgery was necessary in the
      remaining 16 cases. The risk of surgery was distinctly higher within 2 years post
      dilatation than in the next 2 years (26.4% versus 8.3%, respectively; P = 0.078).
      No clear clinical, endoscopic or radiological predictive factors for a successful
      outcome were identified. CONCLUSIONS: Endoscopic pneumatic dilatation is an
      effective and safe procedure to be applied to patients with stenosing Crohn's
      disease, offering a very long-term benefit in a sub-group of patients.

PMID- 14703887
TI  - Endoscopic haemoclip versus heater probe thermocoagulation plus hypertonic saline
      epinephrine injection for peptic ulcer bleeding.
AB  - BACKGROUND: Treating patients of bleeding peptic ulcers with heater probe
      thermocoagulation and haemoclip is considered to be safe and very effective. Yet,
      there is no report comparing the haemostatic effects of endoscopic haemoclip
      versus heater probe thermocoagulation plus hypertonic saline-epinephrine
      injection in these patients. AIM: To compare the clinical outcomes of both
      therapeutic modalities in patients with peptic ulcer bleeding. METHODS: A total
      of 93 patients with active bleeding or non-bleeding visible vessels were
      randomised to receive either endoscopic haemoclip (n = 46) or heater probe
      thermocoagulation plus hypertonic saline-epinephrine injection (n = 47). Five
      patients from the haemoclip group were excluded because of the inability to place
      the haemoclip. RESULTS: Initial haemostasis was achieved in 39 patients (95.1%)
      of the haemoclip group and 47 patients (100%) of the heater probe group (P >
      0.1). Rebleeding occurred in four patients (10.3%) of the haemoclip group and
      three patients (6.4%) of the heater probe group (P > 0.1). The volume of blood
      transfused after entry into the study, duration of hospital stay, number of
      patients requiring urgent surgery and the mortality rates were not statistically
      different between the two groups. CONCLUSIONS: If the haemoclip can be applied
      properly, the clinical outcomes of the haemoclip group would be similar to those
      of the heater probe group in patients with peptic ulcer bleeding. However, if the
      bleeders are located at the difficult-to-approach sites, heater probe plus
      hypertonic saline injection is the first choice therapy.

PMID- 14703888
TI  - A surgical solution to extrahepatic portal thrombosis and portal cavernoma: the
      splanchnic-intrahepatic portal bypass.
AB  - Three cases of prehepatic portal vein thrombosis, complicated by the clinical
      manifestations of portal hypertension, were successfully treated by surgically
      created splanchnic-intrahepatic portal bypass. Two out of three patients had been
      previously submitted to liver transplantation. No significant morbidity was
      observed and long-term Doppler evaluations proved the patency of the venous
      grafts. Together with the technical aspects of the procedures, the possible role
      of this technique, primarily proposed by De Ville de Goyet in 1992, is discussed
      in relation to the available therapies for the extrahepatic portal vein
      thrombosis.

PMID- 14703889
TI  - Endoscopic clipping of a colocutaneous fistula following necrotizing
      pancreatitis: case report.
AB  - The case described here is of a 73-year-old male patient who developed a
      colocutaneous fistula following necrotizing pancreatitis, diagnosed by imaging
      and treated endoscopically by the application of an endoclip. Pancreatic and
      gastrointestinal fistulas, common complications of surgery for necrotizing
      pancreatitis, frequently require surgical treatment. Colonic perforations are the
      most difficult to treat surgically on account of the risk of peritonitis. A
      technique, namely, endoscopic clips application, has recently been developed to
      close anastomotic leakages and perforations of the oesophagus, stomach and colon.
      In the patient described here, endoscopic repair was technically easy and the
      good result was confirmed within a few days. In order to repair colonic fistulas
      following pancreatitis, application of endoclips could, in our opinion, provide a
      useful therapeutic option, feasible in selected patients.

PMID- 14703890
TI  - A rare case of rofecoxib-induced cholestatic hepatitis.

PMID- 14703891
TI  - Nutrient intake and gastric cancer in residents of Zhoushan Islands, China.

PMID- 14703892
TI  - "Ottorino Rossi" Award 2003.

PMID- 14703893
TI  - Stroke and migraine--the spectrum of cause and effect.
AB  - The relationship of migraine and stroke is complex. Stroke may be coincidental
      with migraine but migraine may confer an increased risk of stroke in women under
      45 years of age and possibly in men who have migraine with aura. Stroke may mimic
      migraine but migraine syndromes may be symptomatic of underlying cerebrovascular
      disorders. True migraine-induced stroke is rare. The mechanisms of stroke induced
      during a migraine attack remain to be determined but probably involve an
      interaction between the dynamic shifts in cerebral blood flow and stroke risk
      factors.

PMID- 14703894
TI  - Instrumental investigations in primary headache. An updated review and new
      perspectives.
AB  - While some instrumental techniques are clearly useful for differentiating
      symptomatic forms from primary headache, the usefulness of certain other
      techniques, neurophysiological investigations in particular, in clinical practice
      is still debated. A Task Force of the European Federation of Neurological
      Societies has recently proposed guidelines and recommendations on the use of
      neurophysiological tests and neuroimaging procedures in non-acute headache. This
      article reviews many of the most important literature references relevant to this
      topic and looks at the prospects for future research.

PMID- 14703896
TI  - Anticopper efficacy of captopril and sodium dimercaptosulphonate in patients with
      Wilson's disease.
AB  - The aim of this study was to explore and compare initial treatment effects of
      captopril (Tensiomin) and sodium dimercaptosulphonate (DMPS) on a relatively
      large series of Wilson's disease inpatients. Two important markers of anticopper
      efficacy: serum sulphydryl and 24 h urinary copper levels in the patients were
      evaluated before and after treatment. The patients were randomly subdivided into
      4 groups to allow statistical analysis (ANOVA) of the values recorded. The
      protocol was an open-label study of all the patients treated for 8 weeks (i.e.,
      all the patients except those in the no-drug group), and a further six-month
      follow-up (post hospitalization) of the 14 patients administered captopril.
      Several copper-related variables were studied to evaluate the effect of the drugs
      on copper, and several biochemical and clinical variables were studied to
      evaluate potential toxic effects. Captopril was found to have a significant
      anticopper effect and did not markedly raise serum sulphydryl levels within this
      limited patient sample; the anticopper efficacy of captopril was, however, found
      to be markedly lower than that of DMPS; DMPS was found to raise the patients'
      serum sulphydryl and urinary copper levels. Evaluation of data from individual
      patients revealed evidence of a toxic side effect in only 1 patient, treated with
      DMPS, who exhibited transiently raised serum alanine aminotransferases, while no
      serious adverse events, upstanding syncope, irritating cough and leukopenia
      induced by captopril were noted. The results obtained in this four-group sample
      suggest that captopril might be a mild anticopper agent for Wilson's disease,
      possibly relieving the hepatic portal hypertension, but that DMPS has a greater
      field of anticopper efficiency than captopril. The authors also discuss recent
      experience of the overall treatment in China.

PMID- 14703895
TI  - Alzheimer's disease linking neurodegeneration with neurodevelopment.
AB  - An association has recently been suggested between several of the genes and
      proteins that play a central role in early neuronal development, particularly in
      neuronal migration and axon elongation, and Alzheimer's disease (AD). This paper
      reviews the work of several investigators who have hypothesised the involvement
      of three pathways known to be active participants in neuronal maturation (those
      involving Notch, Reelin, and Wnt intracellular signalling) and also in the
      neurodegenerative events underlying AD. The choice of these intracellular
      pathways is based on the observation that there exist several points of
      convergence among these systems and amyloid precursor protein processing and
      neurofibrillary tangle formation. Pharmacological manipulation of the
      Notch/Wnt/Reelin intracellular signalling pathways may thus represent a novel
      approach to the regulation of neurodegenerative processes in AD.

PMID- 14703897
TI  - Cinnarizine in migraine prophylaxis: efficacy, tolerability and predictive
      factors for therapeutic responsiveness. An open-label pilot trial.
AB  - The efficacy and tolerability of cinnarizine (75 mg, at bedtime) in migraine
      prophylaxis and the presence of possible predictive factors for therapeutic
      responsiveness were evaluated in an open-label pilot trial. Eighty consecutive
      outpatients suffering from migraine with or without aura participated in the
      study. After 12 weeks of therapy, 55 patients experienced a greater than 66%
      reduction in headache frequency and were considered responders. A significant
      reduction in the number of migraine days (mean reduction 58 +/- 8%) and in intake
      of medication to treat acute attacks (mean reduction 55 +/- 11%) was also
      observed. Cinnarizine was well tolerated, as documented by the low number of
      adverse effects. Failure to respond to previous prophylactic treatments was a
      negative predictive factor correlated with a poor prognosis. This study, even
      bearing in mind its limitations as an open-label trial, suggests that cinnarizine
      might be an effective prophylactic anti-migraine agent. The clinical
      characteristics of migraine patients do not help to predict response to
      treatment.

PMID- 14703898
TI  - Behavioural disorders in adolescents with early-treated congenital
      hypothyroidism.
AB  - This study analyses the possible risk factors for the on-set of behavioural
      disorders and psychiatric disturbances in a group of 30 early-treated congenital
      hypothyroidism (CH) subjects (12 children and 18 adolescents) compared with a
      control group of 116 age-matched normal subjects (58 children and 58
      adolescents). The study also allowed us to evaluate the possible age at onset of
      behavioural disorders. Both the sample's and the controls' behaviours were
      assessed using a specific diagnostic instrument: Achenbach's and Edelbrock's
      Child Behaviour Checklist (CBCL). A clinical structured interview, the Diagnostic
      Interview for Children and Adolescents--Revised (DICA-R) was also administered to
      18 adolescents with early-treated CH, in order to determine the presence of
      psychopathological disturbances. In accordance with literature data, the children
      and adolescents with early-treated CH showed more behavioural problems than age
      matched, normal controls. In the children, a statistically significant difference
      versus the controls emerged only in their higher delinquent behaviour score,
      while the adolescents gave, on the CBCL, significantly higher scores compared
      with controls in the withdrawal, anxiety/depression, thought problems, attention
      problems and aggressive behaviour scales. In the DICA-R, 44% of adolescents with
      early-treated CH showed symptoms of anxiety disorder, in particular, separation
      anxiety disorder with phobic components; 16% showed mood disorder and depression
      and 11% showed behavioural disorders with attention deficit.

PMID- 14703899
TI  - Differences in the EMG pattern of leg muscle activation during locomotion in
      Parkinson's disease.
AB  - In this pilot study, EMG patterns of leg muscle activation were studied in five
      parkinsonian patients with (B1) and five without (B2) freezing. Gastrocnemius
      medialis (GM) and tibialis anterior (TA) activity was analysed, by means of
      surface electromyography (EMG), during treadmill walking at two different belt
      speeds. Both groups showed reduced GM activity and an overactive TA at the lower
      speed compared with controls. Upon increasing the speed, the B2 patients showed a
      marked GM response (increment index 100%), while a moderate change was observed
      in the B1 group. Poor recruitment of the GM characterises parkinsonian gait in
      general; this pattern is much more marked in parkinsonian patients with freezing
      of gait, who show a loss of GM adaptation to variation of locomotion speed.

PMID- 14703900
TI  - Organic mercury levels among the Yanomama of the Brazilian Amazon Basin.
AB  - The Catrimani River basin in northern Brazil is the home of the Yanomama and has
      been the site of renegade gold mining since 1980. Gold-mining operations release
      inorganic mercury (Hg) into the environment where it is organified and
      biomagnified in aquatic ecosystems. Ingestion of mercury-contaminated fish poses
      a potential hazard to fish-eating populations such as the Yanomama. We surveyed
      Hg levels in Yanomama villagers living near mined and unmined rivers in 1994 and
      1995, and analyzed Hg levels in piranha caught by villagers. In 1994, 90 Yanomama
      Indians from 5 villages and in 1995, 62 Yanomama Indians from 3 villages
      participated in the studies. Four villages surveyed in 1994 were located directly
      on the Catrimani River, approximately 140-160 km downstream from past gold-mining
      activities. The other village surveyed in 1994 was situated on the unmined
      Ajarani River. In 1995, 2 of the Catrimani River villages were revisited, and a
      third Yanomama village, on the unmined Pacu River, was surveyed. Blood organic
      mercury levels among all villagers surveyed ranged from 0 to 62.6 microg L(-1)
      (mean levels in each village between 21.2 microg L(-1) and 43.1 microg L(-1)).
      Mercury levels in piranha from the mined Catrimani River ranged from 235 to 1084
      parts per billion (ppb). Nine of 13 piranhas, measuring 30 cm or longer had total
      mercury levels which exceeded mercury consumption limits (500 ppb) set by both
      the World Health Organization and the Brazilian Ministry of Health. Unexpectedly,
      high mercury levels were also observed in fish and villagers along the unmined
      Ajarani and Pacu Rivers suggesting that indirect sources may contribute to
      environmental mercury contamination in the Amazon basin.

PMID- 14703901
TI  - Hair element concentrations in females in one acid and one alkaline area in
      southern Sweden.
AB  - Concentrations of 34 trace elements in hair have been determined in 47 females
      from an acid region in southern Sweden, who were compared with 43 females from an
      alkaline area. The concentrations of these elements in hair and drinking water
      were determined by inductively coupled plasma optical emission spectroscopy and
      inductively coupled plasma mass spectrometry. The hair concentrations of boron
      and barium were significantly higher (p < 0.001) in hair samples from the acid
      region, the hair levels of calcium, strontium, molybdenum, iron, and selenium
      were significantly higher (p < 0.001) in the alkaline region. For some metals,
      e.g. calcium, lead, molybdenum, and strontium, there were positive correlations
      between the concentrations in hair and water (rs = 0.34-0.57; p < or = 0.001),
      indicating the importance of intake from minerals in water. The increased ratio
      of selenium/mercury concentrations in hair samples obtained in the alkaline
      district (p < 0.001) indicates that these subjects may have better protection
      against the toxic effects of mercury.

PMID- 14703902
TI  - Loss of plant species richness and habitat connectivity in grasslands associated
      with agricultural change in Finland.
AB  - The drastic loss of seminatural grasslands and the decrease in species diversity
      in Europe during the 20th century are closely linked to social-economic factors.
      Development in agricultural production drives land-use changes, and thus controls
      the capacity of landscapes to maintain biodiversity. In this study, we link
      agricultural production changes to landscape fragmentation and species diversity.
      Our results show that the termination of grazing on seminatural grassland caused
      significant changes in landscape structure and a decline in the number of
      vascular plant species. The decline of grazed grasslands has been driven mainly
      by farm-level economic efficiency and profitability interests, which have been
      connected with agricultural policy measures. Since 1995, when Finland joined the
      European Union, the area of grazed patches in our study area has again increased
      as a result of a support scheme for the management of seminatural grasslands.

PMID- 14703903
TI  - Flooding patterns of the Okavango Wetland in Botswana between 1972 and 2000.
AB  - The inundated area of the Okavango Delta changes annually and interannually. The
      variability relates to regional precipitation over the catchment area in the
      Angolan highlands, and to local rainfall. The patterns of the wetland were
      captured using more than 3000 satellite images for the period 1972 to 2000, near
      daily NOAA AVHRR data for 1985-2000, and less frequent images of the Landsat
      sensors from 1972 onwards. One AVHRR image for every 10-day period was classified
      into land and water using an unsupervised classification method. Evaluation
      against Landsat TM and ERS2-ATSR data indicate an agreement of 89% for the size
      of estimated inundation area. Results show that the wetland area has varied
      between approximately 2450 km2 and 11400 km2 during the last 30 years.

PMID- 14703904
TI  - Effective biological control of Salvinia molesta in the Senegal River by means of
      the weevil Cyrtobagous salviniae.
AB  - The invasion of Salvinia molesta in the Lower Senegal River Delta in Mauritania
      and Senegal in 1999 posed a serious threat to the socioeconomic conditions of the
      local people as well as to wetland biodiversity. Eventually, an effective
      biological control of S. molesta was obtained by means of the weevil Cyrtobagous
      salviniae, which was introduced in the river in Senegal and Mauritania in May
      2000 and in Senegal in April 2001. In October 2001, it became apparent that the
      weevils were doing a magnificent job. The color of the plants was turning from
      green to dark-brown or black, and subsequently the plants started to sink to the
      bottom. Detailed monitoring of the dispersal of C. salviniae in November-December
      2001 confirmed the visual observations of the outcome of biological control. In
      April 2002, it could be concluded that S. molesta was no longer a problem in the
      Senegal River.

PMID- 14703905
TI  - Desert locust control in ecologically sensitive areas: need for guidelines.
AB  - Chemical control of desert locust (DL) is carried out over large areas of land,
      covering a range of different landscapes and ecosystems. There are no real
      restrictions for spraying in or close to environmentally sensitive areas and
      awareness of sensitivity is not always obvious to the people involved in control.
      However, concern about environmental issues in connection with DL control is
      growing and clear guidelines are needed. The objectives were: to identify and
      delineate areas particularly sensitive to pesticide contamination in northeastern
      Africa, e.g. protected areas, wetlands, populated places, oases, and areas with
      concentrations of migratory birds. These areas were matched with actual DL
      control during 1986-1998. The conclusion is that chemical control occurred in
      environmentally sensitive areas especially wetlands, e.g. temporary waters and
      mangroves; close to human settlements; and, to some extent, in or near protected
      areas and areas with numerous migratory birds.

PMID- 14703906
TI  - Forest cover of insular Southeast Asia mapped from recent satellite images of
      coarse spatial resolution.
AB  - The study provides an example of mapping tropical forest cover from SPOT
      Vegetation satellite images of coarse spatial resolution (1 km) for the subregion
      of insular Southeast Asia. A satellite image mosaic has been generated from
      satellite images acquired for the period 1998 to 2000. Forest cover has been
      mapped by unsupervised digital classification. The mapping result has then been
      compared to selected forest maps from the subregion, demonstrating the potential
      to provide basic information on forest area extent and distribution, but also on
      massive forest cover change in the subregional context. Forest area estimates
      derived from the map for the subregion have been found comparable to those
      compiled by FAO. The results indicate that many of the remaining tropical forests
      in Southeast Asia, rich in timber resources and biodiversity, may be lost in the
      near future if deforestation continues at present or previous rates.

PMID- 14703907
TI  - Shifts in winter distribution in birds: effects of global warming and local
      habitat change.
AB  - As global warming intensified toward the end of the 20th century, there was a
      northward shift in winter ranges of bird species in Cape Cod, Massachusetts, USA.
      These poleward shifts were correlated to local increases in minimum winter
      temperatures and global temperature anomalies. This evidence, plus other recent
      results, suggests that during the last two decades global warming has led to
      massive and widespread biogeographic shifts with potentially major ecological and
      human consequences. Local habitat changes associated with urban sprawl affected
      mainly forest birds with more northern winter distributions. In Cape Cod, the
      effects of warming on bird distributions are more substantial at the start of the
      21st century, than those of habitat alteration, but as urban sprawl continues its
      importance may rival that of global warming.

PMID- 14703908
TI  - Marine ecosystem appropriation in the Indo-Pacific: a case study of the live reef
      fish food trade.
AB  - Our ecological footprint analyses of coral reef fish fisheries and, in
      particular, the live reef fish food trade (FT), indicate many countries' current
      consumption exceeds estimated sustainable per capita global, regional and local
      coral reef production levels. Hong Kong appropriates 25% of SE Asia's annual reef
      fish production of 135 260-286 560 tonnes (t) through its FT demand, exceeding
      regional biocapacity by 8.3 times; reef fish fisheries demand out-paces
      sustainable production in the Indo-Pacific and SE Asia by 2.5 and 6 times. In
      contrast, most Pacific islands live within their own reef fisheries means with
      local demand at < 20% of total capacity in Oceania. The FT annually requisitions
      up to 40% of SE Asia's estimated reef fish and virtually all of its estimated
      grouper yields. Our results underscore the unsustainable nature of the FT and the
      urgent need for regional management and conservation of coral reef fisheries in
      the Indo-Pacific.

PMID- 14703909
TI  - Economic values and corporate financial statements.
AB  - Corporate financial statements do not include environmental values. This
      deficiency has contributed to the criticism that company managers do not include
      environmental impacts in the internal decision-making process. The accounting
      profession has not developed effective environmental reporting guidelines. This
      situation contributes to a second problem: the apparent inability of corporate
      reports to provide useful information to external parties. It has been suggested
      that by using nonmarket valuation methodologies, financial statements can be used
      to measure progress toward sustainable development. Nonmarket valuations are not
      generally accepted by the accounting profession. They are too subjective to
      support effective decisions, and too costly to obtain. Furthermore, demand for
      this sort of information appears small. Some of these issues may be resolved over
      time. The most serious challenge, however, concerns how enhanced financial
      reports would be used. Financial statements are supposed to help investors assess
      the amount, timing, and uncertainty of future cash flows. A substantial portion
      of environmental value is based on nonuse benefits, much of which will never be
      realized in company cash flows. In other words, the role of financial statements
      would have to change. Furthermore, since there is no general agreement as to the
      meaning of "sustainable development," efforts to operationalize the term have
      been fraught with difficulty. Moreover, monetization of environmental values
      could jeopardize their preservation, leaving some to question the overall
      objective of this form of reporting. For these reasons, while it is to be hoped
      that better reporting of environmental impacts will be forthcoming, the greatest
      advances will likely be outside the financial statements themselves.

PMID- 14703910
TI  - Allocation of river flows for restoration of floodplain forest ecosystems: a
      review of approaches and their applicability in Europe.
AB  - Floodplain forests are flood-dependent ecosystems. They rely on well-timed,
      periodic floods for the provision of regeneration sites and on tapered flood
      recession curves for the successful establishment of seedlings. These overbank
      flood events are described as "regeneration flows." Once floodplain forest trees
      are established, in order to grow they also require adequate, although variable,
      river stage levels or "maintenance flows" throughout the year. Regeneration flows
      are often synonymous with flood flows and only occur periodically. There is a
      disparity between this need for varied interannual flows over the decadal time
      frame and the usual annual cycle of flow management currently used by most river
      management agencies. Maintenance flows are often closer to established minimum
      flows and much easier to provide by current operational practices.A number of
      environmental flow methodologies, developed in North America, Australia, and
      South Africa are described in this review. They include the needs of the
      floodplain environment in the management and allocation of river flows. In North
      America, these methodologies have been put into practice in a number of river
      basins specifically to restore floodplain forest ecosystems. In Australia and
      South Africa, a series of related "holistic approaches" have been developed that
      include the needs of floodplain ecosystems as well as in-channel ecosystems. In
      most European countries, restoration of floodplain forests takes place at a few
      localized restoration sites, more often as part of a flood-defense scheme and
      usually not coordinated with flow allocation decisions throughout the river
      basin. The potential to apply existing environmental flow methodologies to the
      management of European floodplain forests is discussed.

PMID- 14703911
TI  - Operational indicators for measuring agricultural sustainability in developing
      countries.
AB  - This paper reviews relevant literature on the sustainability indicators
      theoretically proposed and practically applied by scholars over the past 15
      years. Although progress is being made in the development and critical analysis
      of sustainability indicators, in many cases existing or proposed indicators are
      not the most sensitive or useful measures in developing countries. Indicator
      selection needs to meet the following criteria: relative availability of data
      representing the indicators, sensitivity to stresses on the system, existence of
      threshold values and guidelines, predictivity, integratability and known response
      to disturbances, anthropogenic stresses, and changes over time. Based on these
      criteria, this paper proposes a set of operational indicators for measuring
      agricultural sustainability in developing countries. These indicators include
      ecological indicators involving amounts of fertilizers and pesticides used,
      irrigation water used, soil nutrient content, depth to the groundwater table,
      water use efficiency, quality of groundwater for irrigation, and nitrate content
      of both groundwater and crops. Economic indicators include crop productivity, net
      farm income, benefit-cost ratio of production, and per capita food grain
      production. Social indicators encompass food self-sufficiency, equality in food
      and income distribution among farmers, access to resources and support services,
      and farmers' knowledge and awareness of resource conservation. This article
      suggests that the selection of indicators representing each aspect of
      sustainability should be prioritized according to spatial and temporal
      characteristics under consideration.

PMID- 14703912
TI  - Modeling the production and uses of biological resources from the viewpoint of
      energy flow in a rural village in Sichuan, China.
AB  - This study aimed at clarifying the impact of deforestation and afforestation on
      the quality of life in a village in Sichuan Province, China. We devised a
      conceptual model of bioresource production and use based on quantified energy
      flow. The basic structure of the model has three sectors: production, use, and
      externals. We developed comprehensive methodology to quantify the model.
      Bioresource use per person in 1997 was 3.7 GJ for food, 10.2 GJ for fodder, 0.2
      0.4 GJ for building material, 12.8 GJ for fuel, and 1.8 GJ for fertilizer,
      totaling 28.6-28.8 GJ. We used four environmental indicators to evaluate
      bioresource production and use: a biological productivity indicator, a use
      efficiency indicator, a supply-demand balance indicator, and a self-sufficiency
      indicator. Use of these indicators showed that supply-demand balance of fuel was
      dramatically improved from 30% to 85% by afforestation, but 99% of bioresource
      use still depends on domestic products. Thus, it is necessary to improve
      biological productivity and promote the efficient use of bioresources to achieve
      sustainable living in the area. Massive deforestation in the 1950s caused a
      direct shortage of building material and fuel wood. The shortage of wood led to a
      stagnation in the rebuilding of houses, and fuel wood was substituted with crop
      residues. Because crop residues had been used for fertilizer and fodder, their
      use as fuel caused a shortage of fertilizer and fodder. This was an indirect
      impact of deforestation on people's quality of life.

PMID- 14703913
TI  - Impact of fencing on the recovery of the ground flora on heavily eroded slopes of
      a deciduous forest.
AB  - This paper seeks to outline early stages in the recovery of forest ground flora
      on eroded slopes impacted by recreation activities and to suggest how these data
      might be applied in the formulation of management policies for forest recreation
      areas. Based on a fencing experiment in the Sonian Forest near Brussels, we
      investigated whether, over a 6-year period, the vegetation was able to recover
      after having been destroyed by recreation use. Short-term trends in overall
      species composition were already observable during this 6-year study. Species
      recovery on eroded hills was related to slope, aspect, and soil type. During the
      considered time scale, the proportion of hemicryptophytes and the number of
      ancient forest species increased significantly. A downward trend was detected for
      Ellenberg's nitrogen and temperature indexes and for the proportion of
      therophytes and pioneer plants of disturbed places. Changes in species'
      frequencies suggest six recovery strategies: early, late, expanding,
      disappearing, transient, and fluctuating species. Aside from seedling
      reproduction from overstory influences, Luzula sylvatica appeared to be the most
      resilient of the species identified in the study since this species has the
      highest global frequency in our sampling plots and has increased its cover during
      the study period. Study results indicate that (1) protection from recreation has
      initiated the recovery of species in the herb layer, but (2) it may take a long
      time before vegetation previously present in the ground flora may recover in both
      density and species composition.

PMID- 14703914
TI  - Recovery of the benthic macroinvertebrate community in a small stream after long
      term discharges of fly ash.
AB  - Recovery of the benthic macroinvertebrate community in a small east Tennessee
      stream impacted by fly ash discharges from a power plant was investigated over a
      period of 6.5 years. The rate of recovery was greatest in the first 2 years after
      an initial 75% reduction in coal use led to a similar reduction in ash discharges
      and associated contaminants; further recovery followed after all fly ash
      discharges ceased. Recovery of the stream progressed through two phases. In the
      first phase, which lasted for approximately the first 2 years, most density and
      richness metrics increased considerably. In the second phase of recovery, the
      increases in metric values were followed by declines before fluctuating in and
      out of the lower reference ranges for the metrics. Detrended correspondence
      analyses and indicator species analyses showed that changes in species
      composition and community structure were ongoing throughout the second phase.
      Thus, the first phase was characterized by species additions, while the second
      phase involved species replacements and shifts in community dominants. Further
      recovery of the macroinvertebrate community will probably depend on additional
      flushing of fly ash deposits from the streambed and flood plain, because their
      continued presence reduces habitat quality in the stream and serves as a
      potential source of contaminants. Further recovery also may be limited by the
      availability of vagile species in nearby watersheds.

PMID- 14703915
TI  - Agricultural land use effects on sediment loading and fish assemblages in two
      Minnesota (USA) watersheds.
AB  - We examined the relationship between water quality and fish communities within
      two agricultural areas using a computer simulation model. Our analyses focused on
      a coolwater stream, Wells Creek in southeastern Minnesota, and a warmwater
      stream, the Chippewa River in western Minnesota. We used the Agricultural
      Drainage and Pesticide Transport (ADAPT) model in relation to land use to
      calculate instream suspended sediment concentrations using estimates of sediment
      delivery, runoff, baseflow and streambank erosion, and quantified the effects of
      suspended sediment exposure on fish communities. We predicted the effects of
      agricultural practices on stream fish communities under several possible land use
      scenarios, with reference to current conditions. Land use changes led to
      reductions in sediment loading of up to 84% in Wells Creek and 49% in the
      Chippewa River. The reduction in sediment loading across scenarios may be
      directly related to a reduction in runoff by about 35% in both study areas. We
      found a 98% decrease in "lethal" concentrations of suspended sediment on fish in
      Wells Creek with an increase in conservation tillage, riparian buffers, and
      permanent vegetative cover. However, the effects of suspended sediment did not
      significantly decrease in the Chippewa River. This difference between study areas
      was likely due to differences in tolerance to suspended sediment between
      coolwater and warmwater fish communities and differences in topography, runoff
      and bank erosion between the two streams.

PMID- 14703916
TI  - Competitive displacement of trees in response to environmental change or
      introduction of exotics.
AB  - Various global change factors such as natural and anthropogenic climate change,
      tropospheric ozone, CO2, SO2, and nitrogen deposition affect forest growth, but
      in species-specific ways. Since even small differences in growth rates between
      competing species can lead to eventual competitive exclusion, it is important to
      know the rate at which displacement might occur. Similarly, invasive species may
      displace native species and cause their extinction. A simulation study of
      displacement velocity was conducted. Competitive displacement between pairs of
      similar tree species in which one species has a growth advantage produced
      trajectories that fit an exponential decay model, leading to the use of the half
      life as a useful summary statistic. At any given level of growth differential,
      the half-life for shade-tolerant species was found to be much longer than for
      shade-intolerant species due to the ability of shade-tolerant species to survive
      even when their growth is very slow. Trees with longer life-spans also persisted
      longer, but this effect was weaker than the shade-tolerance effect. Disturbances
      speeded up displacement by increasing tumover. For short-lived, intolerant
      species with a 20% disturbance rate and 20% growth suppression, the estimate of
      an approximately 100-year half-life could be considered a precipitous rate of
      decline, with a risk of extinction at about 500 years. In the absence of
      disturbance, and with a 20% growth reduction or differential between competing
      species, half-lives for species replacement ranged from 100+ to nearly 800 years.
      With lesser growth differentials, half-lives are much longer. Such gradual
      competitive displacement processes will be very difficult to detect in the field
      over periods of even decades. Results of this study have implications for exotic
      species invasions. It is predicted that intact forest is not truly resistant to
      invasion, but that invasion of shade-tolerant tree species should be very slow.
      Invasion of shade-intolerant species is predicted to be accelerated by
      disturbance, as has been frequently observed. Results of the simulations were
      supported by data compiled from several parts of the world.

PMID- 14703917
TI  - Analysis of scavengers' activities and recycling in some cities of Nigeria.
AB  - The state of solid waste recycling by scavengers in Onitsha, a heavily commercial
      city in Anambra State, and some other urban areas such as Nsukka, Enugu, and Port
      Harcourt was analyzed. Data were obtained through interviews of scavengers who
      deal with recyclables. Although the activities of scavengers are sub-optimal,
      they can have a great impact on Nigerian economy with respect to resource
      conservation, creation of job opportunities, and reduction of the magnitude of
      waste disposal problems. A cost analysis is presented to compare the different
      forms of recycling utilized by municipal solid waste management. It is shown that
      a well-planned recycling program with recycling and composting would result in
      18.6% savings in waste management costs and 57.7% in landfill avoidance costs.
      However, if the compost materials are not recycled, the corresponding savings in
      cost become 8.6% and 28.6%, respectively. The option with the lowest cost
      involves encouraging individual households to separate at the source their
      recyclables, which are bought by scavengers. This results in 78.0% savings in
      waste management cost and 79.5% landfill avoidance cost. A low-cost approach
      aimed at the integration of scavenging activities into conventional solid waste
      management is presented.

PMID- 14703918
TI  - Applications of numerical sediment quality targets for assessing sediment quality
      conditions in a US Great Lakes Area of Concern.
AB  - Contaminated sediments are receiving increasing recognition around the world,
      leading to the development of various sediment quality indicators for assessment,
      management, remediation, and restoration efforts. Sediment chemistry represents
      an important indicator of ecosystem health, with the concentrations of
      contaminants of potential concern (COPCs) providing measurable characteristics
      for this indicator. The St. Louis River Area of Concern (AOC), located in the
      western arm of Lake Superior, provides a case study for how numerical sediment
      quality targets (SQTs) for the protection of sediment-dwelling organisms can be
      used to support the interpretation of sediment chemistry data. Two types of SQTs
      have been established for 33 COPCs in the St. Louis River AOC. The Level I SQTs
      define the concentrations of contaminants below which sediment toxicity is
      unlikely to occur, whereas the Level II SQTs represent the concentrations that,
      if exceeded, are likely to be associated with sediment toxicity. The numerical
      SQTs provide useful tools for making sediment management decisions, especially
      when considered as part of a weight-of-evidence approach that includes other
      sediment quality indicators, such as sediment contaminant chemistry and
      geochemical characteristics, sediment toxicity, and benthic macroinvertebrate
      community structure. The recommended applications of using the numerical SQTs in
      the St. Louis River AOC include: designing monitoring programs, interpreting
      sediment chemistry data, conducting ecological risk assessments, and developing
      site-specific sediment quality remediation targets for small, simple sites where
      adverse biological effects are likely. Other jurisdictions may benefit from using
      these recommended applications in their own sediment quality programs.

PMID- 14703919
TI  - An evaluation of vernal pool creation projects in New England: project
      documentation from 1991-2000.
AB  - Vernal pools are vulnerable to loss through development and agricultural and
      forestry practices owing to their isolation from open water bodies and their
      small size. Some vernal pool-dependent species are already listed in New England
      as Endangered, Threatened, or Species of Special Concern. Vernal pool creation is
      becoming more common in compensatory mitigation as open water ponds, in general,
      may be easier to create than wooded wetlands. However, research on vernal pool
      creation is limited. A recent National Research Council study (2001) cites vernal
      pools as "challenging to recreate." We reviewed documentation on 15 vernal pool
      creation projects in New England that were required by federal regulatory action.
      Our purpose was to determine whether vernal pool creation for compensatory
      mitigation in New England replaced key vernal pool functions by assessing project
      goals and documentation (including mitigation plans, pool design criteria,
      monitoring protocols, and performance standards). Our results indicate that
      creation attempts often fail to replicate lost pool functions. Pool design
      specifications are often based on conjecture rather than on reference wetlands or
      created pools that function successfully. Project monitoring lacks consistency
      and reliability, and record keeping by regulatory agencies is inadequate.
      Strengthening of protection of isolated wetlands in general, and standardization
      across all aspects of vernal pool creation, is needed to ensure success and to
      promote conservation of the long-term landscape functions of vernal pools.

PMID- 14703920
TI  - Model-based assessment of aspen responses to elk herbivory in Rocky Mountain
      National Park, USA.
AB  - In Rocky Mountain National Park (RMNP), aspen (Populus tremuloides Michx.) has
      been observed to be declining on elk (Cervus elaphus nelsoni) winter range for
      many decades. To support elk management decisions, the SAVANNA ecosystem model
      was adapted to explore interactions between elk herbivory and aspen dynamics. The
      simulated probability of successful vegetative regeneration for senescent aspen
      stands declines sharply when elk densities reach levels of 3-5 elk/km2, depending
      on model assumptions for the seasonal duration of elk foraging activities. For
      aspen stands with a substantial component of younger trees, the simulated
      regeneration probability declines more continuously with increasing elk density,
      dropping below 50% from densities at 8-14 elk/km2. At the landscape scale,
      simulated aspen regeneration probability under a scenario of extensive seasonal
      use was little affected by elk population level, when this level was above 300
      600 elk (25%-50% current population) over the ca. 107 km2 winter range. This was
      because elk distribution was highly aggregated, so that a high density of elk
      occupied certain areas, even at low population levels overall. At approximately
      current elk population levels (1000-1200 elk), only 35%-45% of senescent aspen
      stands are simulated as having at least a 90% probability of regeneration, nearly
      all of them located on the periphery of the winter range. Successful management
      for aspen persistence on core winter range will likely require some combination
      of elk population reduction, management of elk distribution, and fencing to
      protect aspen suckers from elk browsing.

PMID- 14703921
TI  - Predictive factors for early mortality following liver transplantation.
AB  - AIMS: To retrospectively review our liver transplant performance to identify
      factors that influenced early outcomes and to prospectively test their validity
      in predicting outcomes. METHODS: Clinical records from 190 patients with liver
      transplants (LT; n = 200) performed between 1991 and 1997 were reviewed and the
      data evaluated by univariate and multivariate analyses regarding clinical
      outcome. The prognostic model thus obtained was prospectively evaluated in 55
      patients undergoing transplant between 1999 and 2000. RESULTS: Main indication
      for transplant was post-necrotic cirrhosis (61%), mostly HCV(+). The majority of
      patients were Child-Pugh C status (46%). Post-operative mortality at 3 months was
      15.3%. Risk factors predicting death were: Child-Pugh C status (OR 1.3), pre-LT
      renal insufficiency (OR 5.8), malnutrition (OR 2.9) and technically complex
      surgery requiring cross-clamping with or without bypass (OR 4.9). None of the
      donor factors was significant. Prospectively applied to predict outcome in the 55
      patients, the model had a sensitivity of 80% and a specificity of 88.8% with a
      higher-than-anticipated accuracy with a positive predictive value of 61.5% and a
      negative predictive value of 95.3%. CONCLUSIONS: Pre-LT renal insufficiency is
      the most significant risk factor for early mortality and suggests that LT should
      be performed before evidence of irreversible renal insufficiency becomes
      manifest.

PMID- 14703922
TI  - Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of
      tacrolimus in liver transplant recipients with small-for-size grafts.
AB  - In adult-to-adult living donor liver transplantation (LDLT), the graft volume is
      inevitably much smaller than the ideal liver mass (standard liver volume) for the
      recipient's metabolic demand. Patients with small-for-size grafts are treated
      with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver
      support. However, little is known about the influence of CVVHD on the elimination
      of tacrolimus. The objective of this study was to elucidate the effect of CVVHD
      on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size
      grafts. Three liver transplant recipients (one male and two females) and donors
      (two males and one female) were enrolled in this study. Blood samples from inflow
      port and outflow port were obtained on the first day at the start of CVVHD. Whole
      blood concentrations of tacrolimus were measured immediately using the
      microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no
      significant difference between concentrations of tacrolimus in blood sampled at
      inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three
      recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the
      blood tacrolimus concentration. Adjustment to the dose or dosing interval is not
      required for patients treated with tacrolimus during CVVHD.

PMID- 14703923
TI  - Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant
      lymphoproliferative disorder.
AB  - INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLD) is a
      consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia
      with CD-20 positive lymphocytes. The treatment of PTLD includes
      reduction/withdrawal of immunosuppression and chemotherapy. This study reports
      our center experience with humanized monoclonal antibody against CD-20
      (Rituximab) for the treatment of PTLD. MATERIAL AND METHODS: Eight cases of PTLD
      after solid organ transplantation [six kidney, one kidney/pancreas (KP) and one
      liver] occurred between September 1998 and October 2001. The mean time between
      transplant and the diagnosis of PTLD was 57.3 months (range 3 months to 10 yr).
      Five patients underwent cadaveric transplant, five males and six were Caucasians
      with mean age of 48 yr (range 20-67 yr). RESULTS: The clinical presentation was
      as follows: lymphadenopathy--5, gastrointestinal bleeding--2 and tonsillar
      enlargement--1. The diagnosis was made by a lymph node biopsy in five, a gastric
      ulcer biopsy in two and a tonsillar biopsy in one case. Six of them had
      polymorphous, two had monoclonal B-cell lymphoma, and all were positive for CD
      20. Six were related to EBV, documented by latent membrane protein (LMP) or
      Epstein-Barr encoded RNA (EBER) staining. Immunosuppression at the time of PTLD
      diagnosis consisted of tacrolimus in six cases and cyclosporine A (CsA) in two
      with mycophenolate mofetil (MMF) and azathioprine--3 each and sirolimus--1.
      Rituximab was administered at a dose of 375 mg/m2 once a week for 4 wk. There
      were no side effects seen with this therapy. Immunosuppression was reduced in all
      patients. Complete remission was observed in seven cases (one required two
      courses). One patient who did not respond received chemotherapy. Patients were
      followed for a mean period of 22.5 months (range 10-45 months post-PTLD
      diagnosis. At the last follow-up all eight patients were alive, seven with a
      functioning graft and one on maintenance dialysis. Three of these patients had
      been in remission for more than 2.5 yr. CONCLUSION: Rituximab is an effective
      agent in the treatment of PTLD without the morbidity characteristic of
      chemotherapy. Chemotherapy should be reserved only for those refractory to
      Rituximab therapy.

PMID- 14703924
TI  - Monitoring of human cytomegalovirus infections in heart transplant recipients by
      pp65 antigenemia.
AB  - BACKGROUND: Rapid diagnostic techniques offer the opportunity of early diagnosis
      of human cytomegalovirus (CMV) infection in immunocompromized patients at risk of
      developing CMV disease and syndrome. The use of CMV pp65 antigenemia as a
      predictor of CMV syndrome and disease in heart transplant recipient after
      induction therapy was studied retrospectively. METHODS: One hundred and nineteen
      consecutive heart transplant recipients treated with induction therapy who
      survived more then 14 d were monitored for CMV infection. Ninety-four recipients
      were seropositive for CMV. Twenty-five recipients were seronegative for CMV and
      received grafts from seropositive donors. Pre-emptive therapy was used in
      seropositive patients when CMV pp65 antigenemia was greater than 50 antigen
      positive cells per 2 x 10(5) peripheral blood leukocytes (PBL); prophylactic
      therapy was done only in seronegative recipient matched with seropositive donor.
      RESULTS: High-level CMV pp65 antigenemia (50 antigen-positive cells 2 x 10(5)
      PBL) occurred in 34% (41 of 119) of patients at a median of 44 d following
      transplantation. In seropositive recipients, 16% (15 of 94) of patients developed
      CMV invasive disease or syndrome, and in seronegative recipients 20% (5 of 25) of
      patients developed CMV disease or syndrome. Sixty-six per cent (62 of 94) of CMV
      seropositive patients were identified as not requiring pre-emptive therapy. In
      seropositive and seronegative recipients, the sensibility and negative predictive
      value of the cut-off level of 50 antigen positive cell for CMV disease and
      syndrome was 100%. The specificity was 79% and positive predictive value was 49%.
      CONCLUSION: Because of the excellent sensibility and negative predictive value of
      the cut-off level of 50 antigen positive cell per 2 x 10(5) PBL, application of
      pre-emptive therapy guided by high level of CMV pp65 antigenemia in the context
      of induction therapy allow to omit antiviral therapy in many at risk patients. In
      the context of pre-emptive and prophylactic therapy, the cut-off level of 50
      antigen positive cell do not allow to predict with accuracy the development of
      CMV disease or syndrome.

PMID- 14703925
TI  - The use of daclizumab as induction therapy in combination with tacrolimus and
      mycophenolate mofetil in recipients with previous transplants.
AB  - Clinical trials using daclizumab as induction therapy in combination with
      tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the
      incidence of acute rejection episodes in solid organ transplantation. In an
      attempt to obtain a low rejection rate we proceeded with the use of daclizumab as
      induction therapy, in combination with TAC and MMF for recipients with previous
      transplants. In this study, we analyzed patients who received previous
      transplants, treated with the above immunosuppressive regimen. Group A consisted
      of four patients with previous liver transplants, group B consisted of 16
      recipients with previous kidney transplants and group C consisted of three
      patients with previous simultaneous pancreas-kidney transplants. All patients
      underwent cadaveric kidney transplants except one patient in group B, who
      underwent a pancreas transplant. At 12 months, patient and graft survival for all
      groups was 100 and 100%, respectively. Acute rejection rate was 0% for group A,
      12.5% for group B, and 0% for group C. Daclizumab induction therapy is effective
      for patients with previous transplants and does not appear to increase the risk
      of acute rejection.

PMID- 14703926
TI  - Use of kidneys from hepatitis C seropositive donors shortens waitlist time but
      does not alter one-yr outcome.
AB  - Utilization of hepatitis C seropositive kidney donors remains controversial. We
      examined the use of hepatitis C seropositive donors for renal transplantation.
      Data for creatinine, liver function tests, cold ischemia time, and graft and
      patient survival were analyzed from 20 hepatitis C seropositive recipients
      receiving cadaveric renal allografts from seropositive donors and were compared
      with 20 hepatitis C seropositive recipients receiving allografts from
      seronegative donors. Recipients receiving a kidney from a hepatitis C
      seropositive donor were on the waitlist for 9.9 +/- 1.8 months, compared with
      17.8 +/- 3.3 months for those receiving a kidney from a seronegative donor (p <
      0.05). There were no significant differences in graft or patient survival.
      Incidences of acute cellular rejection and acute tubular necrosis were similar.
      There were no significant differences in creatinine, alanine aminotransferase,
      alkaline phosphatase, or bilirubin values. While there was a significant
      difference in aspartate aminotransferase at 2 wk and 6 months, these differences
      were of questionable clinical importance. In conclusion, donor seropositivity for
      hepatitis C should not preclude renal transplantation into a hepatitis C
      seropositive recipient and utilization of these organs decreases waitlist time
      for hepatitis C seropositive recipients.

PMID- 14703927
TI  - Hepatitis B virus vaccination of recipients and donors of allogeneic peripheral
      blood stem cell transplantation.
AB  - BACKGROUND: The aim of this study was to determine the role of hepatitis B virus
      (HBV) vaccination as defined by the seroconversion to hepatitis B surface
      antibody (anti-HBs) positivity in peripheral blood stem cell transplants.
      METHODS: A total of 65 recipients and their donors were enrolled in this study.
      Recipients were divided into four distinct groups. Group 1 consisted of
      individuals who were vaccinated, group 2 consisted of individuals who were
      naturally immunized, group 3 consisted of individuals who were HBs-Ag positive,
      and group 4 consisted of individuals who were HBV naive and not vaccinated.
      RESULTS: Eighty-eight percent of the HBV-vaccinated recipients (14 of 16), who
      had vaccinated-donors, seroconverted to anti-HBs positivity. Eighty-three percent
      of HBV-naive recipients (five of six), who received stem cells from HBV-immune
      donors, seroconverted to anti-HBs positivity. Two of the four HBs-Ag positive
      recipients with HBV-immune donors seroconverted to anti-HBs positivity after
      transplantation. Fifty-seven percent of previously vaccinated-recipients (eight
      of 14) lost detectable anti-HBs antibody following transplantation. Finally, 31%
      of HBV-naive recipients with HBV-naive donors acquired a de novo HBV infection.
      CONCLUSIONS: (i) Hepatitis B virus immunization of recipients of allogeneic
      hematopoietic cell transplantation results in an effective antibody response.
      (ii) The HBV-immune status of the donor plays an important role in post
      transplantation HBs-Ab on seroconversion. (iii) Systematic re-immunization of
      recipients will be necessary to maintain HBV immunity in long-term serving
      recipients.

PMID- 14703929
TI  - Human herpesvirus 8 and Epstein-Barr virus-related monotypic large B-cell
      lymphoproliferative disorder coexisting with mixed variant of Castleman's disease
      in a lymph node of a renal transplant recipient.
AB  - Human herpesvirus 8 (HHV8) has been related to some malignant
      lymphoproliferations, including post-transplant lymphoproliferative disorders
      (PTLD). We describe a case of a HHV8 and Epstein-Barr virus (EBV) positive large
      B-cell lymphoproliferation coexisting with Castleman's disease in the same lymph
      node of a long-term renal transplant recipient. Biopsy revealed mixed type of
      Castleman's disease and anaplastic cells showing IgA restriction, although
      molecular analysis failed to detect monoclonality. Only large cells were co
      infected by both EBV and HHV8. After reduction of immunosuppression, the lesion
      partially regressed. After 1 yr, local evolution required surgery followed by
      irradiation. The present case represents a unique form of localized monotypic but
      polyclonal large cell PTLD associated with Castleman's disease. It can be added
      to PTLD with HHV8 and EBV co-infection.

PMID- 14703928
TI  - Reduced P-selectin expression on circulating platelets after prolonged cold
      preservation in renal transplantation.
AB  - The uremic state in patients with terminal renal insufficiency is accompanied by
      a bleeding tendency connected with platelet dysfunction. Prolonged cold ischemia
      and inflammatory interactions between leukocytes, platelets and endothelial cells
      contribute to ischemia-/reperfusion (I/R) injury and may impair long-term graft
      survival. We evaluated the influence of the duration of cold preservation time on
      the expression of platelet GPIIb/IIIa and P-selectin and on the formation of
      leukocyte-platelet complexes after kidney transplantation. Fourteen patients
      undergoing kidney transplantation were divided into group I with long
      preservation time (26.6 +/- 1.9 h) and group II with short preservation time (8
      +/- 6.1 h). Five venous blood samples (3 ml) were taken before induction of
      anesthesia, 12 h, 2, 7 and 14 d after transplantation. Surface expression of the
      GPIIb/IIIa, P-selectin and the percentage of platelet-granulocyte complexes were
      quantified by flow cytometry. Additionally blood from seven healthy volunteers
      was analyzed. GPIIb/IIIa and P-selectin expression on circulating platelets were
      significantly decreased in the long and the short-term graft preservation group
      compared with healthy volunteers. A significantly reduced P-selectin expression
      was found in the long-term preservation group compared with the short-term group.
      The percentage of platelet-granulocyte complexes also decreased in both
      preservation groups in the first 2 d after reperfusion and remained in this state
      in the long-term preservation group. Reduced expression of P-selectin on
      circulating platelets may be an indicator of I/R injury after prolonged kidney
      graft preservation.

PMID- 14703930
TI  - First human double hand transplantation: efficacy of a conventional
      immunosuppressive protocol.
AB  - Based on the results achieved in single human hand transplantations, we decided
      to perform the first double hand transplantation with a conventional
      immunosuppressive protocol in a patient with a high potential for functional
      recovery. Two years after transplantation the efficacy and the safety of this
      immunosuppressive protocol are evaluated. The recipient was a 33-yr-old man
      suffering from a traumatic amputation of both hands in 1996. Five HLA-A, -B, and 
      DR mismatches were present with the donor; T and B cell cross-match was negative.
      Immunosuppressive protocol included tacrolimus, prednisone, mycophenolate mofetil
      and, for induction, antithymocyte globulins and then anti CD25 monoclonal
      antibody. Reconstitution of lymphocyte populations proceeded normally. Neither
      anti-HLA antibodies nor chimerism in peripheral blood were detected. Two episodes
      of acute rejection characterized by maculopapular lesions occurred on days 53 and
      82 after transplantation. Skin biopsies revealed a dermal lymphocytic infiltrate.
      Both episodes were completely and rapidly reversed by topical clobetasol and
      increased systemic corticosteroid therapy. The only side-effects related to
      treatment were reversible serum sickness and hyperglycemia. No infectious
      complications and malignancies occurred. No signs of graft-versus-host disease
      have been detected. This case of double hand transplantation shows that
      conventional immunosuppression is effective and safe to ensure survival and
      functional recovery of the grafted limb.

PMID- 14703931
TI  - Successful orthotopic liver transplantation after trimethoprim-sulfamethoxazole
      associated fulminant liver failure.
AB  - Trimethoprim-sulfamethoxazole (TMP-SMZ) is one of the most commonly used
      antibiotics. Although many of its adverse effects are well recognized, TMP-SMZ
      related hepatotoxicity is considered rare and is usually characterized by
      cholestasis or mixed hepatocellular-holestatic reactions. In this study, we
      describe the case of a previously healthy young man with acute fulminant liver
      failure caused by TMP-SMZ. The patient presented with complaints of 'flu-like'
      symptoms with myalgia and fever after taking TMP-SMZ for 7 d for otitis externa.
      The patient subsequently developed fever, worsening jaundice, and a rash on his
      neck and chest. Liver enzymes peaked on day 3 with alanine aminotransferase (ALT)
      11,549, aspartate aminotransferase (AST) 23,289, alkaline phosphatase 245, and
      total bilirubin 10.3 mg/dL, with a conjugated bilirubin of 8.3 mg/dL, prothrombin
      time (PT) 60.5 s, partial normalized ratio (PTT) 49 s, and international
      normalized ratio (INR) 7.5. Of note, acetaminophen level on admission was
      undetectable. Serology for hepatitis A, B, C, cytomegalovirus, HIV,
      toxoplasmosis, and blood cultures were all negative. The patient developed
      hepatic encephalopathy with hallucination on day 4. Laboratory tests revealed a
      serum ammonia level of 190 U, serum creatinine kinase (CK) 10,466 (42 on
      admission), serum creatinine 8.2 mg/dL (1.2 on admission), and significant
      metabolic acidosis. Renal ultrasound was unremarkable. The patient was started on
      hemodialysis for acute renal failure. Meanwhile, liver transplantation assessment
      was also initiated. On day 8 post-admission (15 d after taking TMP-SMZ), the
      patient received a successful orthotopic liver transplant.

PMID- 14703932
TI  - Donor intracaval thrombus formation and pulmonary embolism after simultaneous
      piggyback liver transplantation and aortic valve replacement.
AB  - Pulmonary embolism (PE) is a well known and serious complication that may develop
      after abdominal surgery. Liver transplant recipients are not immune to PE and
      tend to share many of the same risk factors with surgical patients who are
      stricken with this potential fatal complication. Liver transplantation using the
      piggyback (PB) technique is widely accepted, although there are reports of
      technique-specific-related vascular complications. We present a case of a 49-yr
      old male liver transplant recipient who received his graft using the PB while
      simultaneously undergoing aortic valve replacement. His post-operative course was
      complicated by a PE 15 d after his surgery and was the result of an intracaval
      thrombus of the graft liver. The current case should alert clinicians to think of
      a donor intracaval thrombus as a complication of PB liver transplantation and a
      possible source of PE.

PMID- 14703933
TI  - Impairment of the blood-brain barrier can result in tacrolimus-induced reversible
      leucoencephalopathy following heart transplantation.
AB  - Fatal leucoencephalopathy is a rare calcineurin inhibitor-related complication,
      especially in kidney and liver transplant recipients. The only means of clinical
      management reported so far is the discontinuation or reduction in the calcineurin
      inhibitor. We herein report a case of a 37-yr-old male who developed
      leucoencephalopathy 12 wk after heart transplantation and recovered after
      stabilization of metabolism and arterial blood pressure. The findings in this
      case support the hypothesis that tacrolimus-associated neurotoxicity is severely
      increased by an impairment of the blood-brain barrier. Withdrawal of tacrolimus
      was not necessary while other causes of endothelial injury were treated
      successfully.

PMID- 14703934
TI  - Transmission of a pancreatic adenocarcinoma to a renal transplant recipient.
AB  - Transmission of donor tumours in solid organ transplant recipients is rare, but
      has been reported with fatal outcome in some cases depending on the original
      tumour type and location. We report a case of a pancreatic adenocarcinoma of
      donor origin presented as lymphangitis carcinomatosa of the lung in a renal
      transplant recipient 9 months after transplantation, which is likely to have
      contributed to the death of the patient 15 months after transplantation. The
      donor tumour was originally diagnosed on adrenal tissue removed from the donor
      kidney during bench preparation. At the time of the diagnosis this kidney and the
      liver of the multi-organ donor had been transplanted. The liver patient was
      urgently retransplanted within 24 h. The renal recipient opted not to have a
      transplant nephrectomy having been made aware of the risk of tumour transmission.
      The contralateral kidney was discarded. Management of recipients with potential
      transmission of initially undiagnosed donor malignancy is difficult. Early
      transplant nephrectomy may be the safest option.

PMID- 14703935
TI  - Transfusion-associated graft vs. host disease after donor-specific leukocyte
      transfusion before kidney transplantation.
AB  - Transfusion-associated graft vs. host disease (TA-GVHD) is a well-known but rare
      complication that follows infusion of histo-incompatible lymphoid cells, often
      seen in individuals with impaired cellular immunity. However, we present here a
      case report of fatal TA-GVHD in a 'presumed' immunocompetent patient after
      transfusion of a freshly isolated buffycoat from a relative as part of our
      protocol to prepare the patient for living-related kidney transplantation. To
      confirm the diagnosis of TA-GVHD, a polymerase chain reaction was used to detect
      donor cells in various affected tissues. Furthermore, the immune reactivity of
      the patient against donor and vice versa was tested on samples taken before
      transfusion using limiting dilution assays. Our patient received a transfusion
      with blood from a donor who was homozygous at the human leukocyte antigen (HLA)
      class I loci. Despite incompatibility for HLA class II, infused donor T
      lymphocytes were not rejected and became engrafted. The patient did not have
      cytotoxic T lymphocytes to reject the donor cells. DNA polymorphism studies on
      several organ biopsies confirmed the presence of infiltrating cells of donor
      origin. This report illustrates the possibility, in the general patient
      population, of developing TA-GVHD from whole blood transfusion. In the case of
      pre-transplant blood transfusion, the patient and donor have to be HLA-typed and
      special care should be taken in the situation of donor homozygosity for HLA class
      I, even in the presence of HLA class II incompatibility. Protocols in which donor
      specific blood or bone marrow transfusions are given in an attempt to modulate
      the immune system should exclude these combinations.

PMID- 14703936
TI  - The upside down transplant kidney.

PMID- 14703937
TI  - Focus on neuroscience: a merging of minds.

PMID- 14703938
TI  - Preventing and managing resistance in the clinical setting.

PMID- 14703939
TI  - Potency and durability of antiretroviral therapy.

PMID- 14703940
TI  - Adherence and potency with antiretroviral therapy: a combination for success.

PMID- 14703941
TI  - HIV, HAART, and hyperlipidemia: balancing the effects.

PMID- 14703942
TI  - Three-dimensional dose distribution for partial irradiation of rat parotid glands
      with 200kV X-rays.
AB  - PURPOSE: To investigate dose distributions in partial-volume irradiation
      experiments in small experimental animals, in particular the parotid gland of
      rat. MATERIALS AND METHODS: High-resolution magnetic resonance imaging images
      were made that provided the outlines of the parotid glands, which were used to
      design collimators with conformal radiation ports for 100 and 50% cranial/caudal
      partial-volume irradiation. A protocol for absolute dosimetry was designed and
      relative dose measurements were performed. From the three-dimensional
      topographical data and the three-dimensional dose distribution, dose-volume
      histograms were determined. RESULTS: The standard uncertainty of absorbed
      entrance dose was within 3%. Radiochromic film, thermoluminescence dosemeters and
      ionization chamber dose measurements revealed that the relative doses measured
      were in good agreement. The 20-80% penumbra of the beam across the 50% field edge
      was only 0.4 mm at a 6 mm depth. The gradient of the percentage depth dose from
      the skin of the rat to a depth of 12 mm was 1.5% mm(-1). The absorbed doses in
      the cranial 50% and the caudal 50% partial volumes were comparable. This finding
      was reflected in the calculated dose-volume histograms of the different regions,
      which were similar. The dose in the shielded area between the left and right
      ports was about 14% of the dose near the centres of the beams. CONCLUSION: The
      designed set-up showed that irradiation of small volumes could be performed with
      high accuracy allowing the study of differences in radiation damage. Similar
      doses were given to the 50% cranial and 50% caudal gland volumes and, therefore,
      a possible difference in radiosensitivity in these volumes was not a dose effect.
      The approach used was also applicable for the irradiation of small volumes of
      other tissues.

PMID- 14703943
TI  - Influence of high-frequency electromagnetic fields on different modes of cell
      death and gene expression.
AB  - PURPOSE: International thresholds for exposure to non-ionizing radiation leading
      to non-thermal effects were conservatively set by the International Commission on
      Non-Ionizing Radiation Protection (ICNIRP). The aim of this study was to examine
      whether biological effects such as different modes of cell death and gene
      expression modifications related to tumorgenesis are detectable above the
      threshold defined. MATERIALS AND METHODS: Human leukaemia cells (HL-60) grown in
      vitro were exposed to electromagnetic fields (EMF; t 1/2(r) about 1 ns; field
      strength about 25 times higher than the ICNIRP reference levels for occupational
      exposure) leading to non-thermal effects using a high-voltage-improved GTEM cell
      5302 (EMCO) connected to a pulse generator NP20 (C = 1 nF, U(Load) = 20kV). HL-60
      cells were harvested at 0, 24, 48 and 72 h after radiation exposure. Micronuclei,
      apoptosis and abnormal cells (e.g. necrosis) were determined using morphological
      criteria. In parallel, the expression of 1176 genes was measured using Atlas
      Human 1.2. Array. Based on high data reproducibility calculated from two
      independent experiments (> 99%), array analysis was performed. RESULTS: No
      significant change in apoptosis, micronucleation, abnormal cells and differential
      gene expression was found. CONCLUSIONS: Exposure of HL-60 cells to EMFs 25 times
      higher than the ICNIRP reference levels for occupational exposure failed to
      induce any changes in apoptosis, micronucleation, abnormal morphologies and gene
      expression. Further experiments using EMFs above the conservatively defined
      reference level set by the ICNIRP may be desirable.

PMID- 14703944
TI  - Fibronectin and laminin increase resistance to ionizing radiation and the
      cytotoxic drug Ukrain in human tumour and normal cells in vitro.
AB  - PURPOSE: Cell-extracellular matrix (ECM) interactions are thought to mediate drug
      and radiation resistance. Dependence of cell survival, beta1-integrin expression
      and cell cycling on the ECM proteins and beta1-integrin ligands fibronectin (FN)
      and laminin (LA) were examined in malignant and normal cells exposed to the
      cytotoxic drug Ukrain plus/minus irradiation. MATERIALS AND METHODS: Human A549
      lung cancer and MDAMB231 (MDA231) breast cancer cells and normal fibroblasts
      (HSF1) grown on FN, LA, bovine serum albumin (BSA) or polystyrene were treated
      with Ukrain (1 microg ml(-1), 24 h) plus/minus irradiation (2-8 Gy) and the
      effects studied using colony formation assays, flow cytometry (beta1-integrin,
      DNA analysis) and adhesion assays. RESULTS: FN and LA reduced the cytotoxic
      effect of single Ukrain treatment compared with polystyrene and BSA. FN and LA
      also abolished Ukrain-dependent radiosensitization in A549 cells and decreased
      the radiosensitivity of MDA231 and HSF1 cells. Single Ukrain exposure on
      polystyrene significantly reduced beta1-integrin expression and promoted G2-phase
      accumulation of A549 cells. In contrast, Ukrain-treated MDA231 and HSF1 cells
      showed elevated beta1-integrin expression and no Ukrain-specific cell cycle
      effect. Under Ukrain-radiation exposure, irradiation, FN or LA abolished Ukrain
      mediated reduction of beta1-integrin expression and G2-phase accumulation in A549
      cells, whereas in MDA231 cells and fibroblasts beta1-integrin expression and cell
      cycle distribution were stabilized. Cell adhesion to FN or LA was significantly
      impaired (A549) or improved (MDA231, HSF1) upon Ukrain treatment. CONCLUSIONS:
      The data corroborate the findings of other groups that cell adhesion-mediated
      resistance to either single or combined drug and radiation exposure is tightly
      correlated to specific ECM proteins. By demonstrating a strong modulatory impact
      of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, the
      set findings are also highly important for the assessment of drug and radiation
      effects within in vitro cytotoxicity studies. The data give the first mechanistic
      insights into specific FN- and LA-modulated cellular resistance mechanisms as
      well as into the important role for beta1-integrins using the unique cytotoxic
      and radiosensitivity-modifying drug Ukrain.

PMID- 14703945
TI  - Ionizing radiation modules of the expression and tyrosine phosphorylation of the
      focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates
      p130cas and paxillin in A549 human lung carcinoma cells in vitro.
AB  - PURPOSE: Focal adhesion kinase (FAK) is involved in the regulation of many
      cellular processes, including cell survival and death, proliferation and
      migration. The same endpoints are influenced by ionizing radiation (IR).
      Therefore, study was performed to determine the effect of IR on the expression
      and phosphorylation of FAK and two of its substrates, p130cas and paxillin, in
      vitro. MATERIALS AND METHODS: Exponentially growing A549 lung carcinoma cells
      were exposed to 6 Gy X-rays. Protein expression and the extent of tyrosine
      phosphorylation were investigated by immunoprecipitation experiments and Western
      blotting analysis using specific or unspecific phosphotyrosine antibodies.
      Immunofluorescence staining in combination with confocal laser scanning
      microscopy was done to localize the proteins within the cell. RESULTS: Tyrosine
      phosphorylation, of Mr 110 000 150 000 and 65 000-75 000 protein bands, was
      induced within 30 min after exposure to IR. Three of these proteins were
      identified as FAK, p130cas and paxillin. IR induced phosphorylation of FAK
      (tyr397 and tyr925) but did not change FAK expression. Additionally, IR induced
      phosphorylation of paxillin (tyr31 and tyr181) within 30 min and an up-regulation
      of paxillin expression 2-6 h after exposure. Furthermore, a higher amount of
      phosphorylated p130cas was found in irradiated cells. Immunofluorescence staining
      demonstrated that in A549 cells, all three proteins colocalize at sites of focal
      adhesions at the cytoplasmic face of the cell membrane and to lamellopodia.
      CONCLUSIONS: The data indicate that these focal adhesion-associated proteins are
      modulated by IR and thus are likely to play a role in the cellular response to
      IR. These proteins might represent attractive targets to modulate FAK-initiated
      signalling pathways, which may be involved in improved radioresistance and,
      furthermore, in important pathological phenomena such as tumour growth and
      metastatic phenotypes.

PMID- 14703946
TI  - Role of Ca2+ in radiation-induced damage in murine splenocytes.
AB  - PURPOSE: To address the links between calcium, peroxidation, cell damage and
      death and the response of the enzymes involved in free radical metabolism, in
      splenocytes of mice irradiated with gamma-rays. MATERIALS AND METHODS:
      Splenocytes of Swiss albino mice were irradiated with various doses (0-7 Gy) of
      gamma-rays (60Co) at a dose-rate of 0.0575 Gy s(-1). Membrane peroxidation and
      fluidity were determined by the thiobarbituric acid-reactive substances (TBARS)
      method, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH),
      respectively. Apoptosis was analysed by nucleosomal ladder formation and activity
      of NF-kappaB by electrophoretic mobility shift assay (EMSA). The specific
      activities of the antioxidant enzymes, lactate dehydrogenase (LDH), levels of
      nitric oxide (NO*) and glutathione were determined spectrophotometrically.
      Modulatory effects of Ca2+ were examined at 3 Gy using different concentrations
      (1, 3 and 5 mM) in the presence or absence of the ionophore A23187. RESULTS:
      Irradiation of splenocytes resulted in enhanced peroxidative damage. membrane
      fluidity, apoptosis and DNA binding activity of NF-kappaB. The specific
      activities of LDH and antioxidant enzymes superoxide dismutase (SOD), DT
      diaphorase (DTD), glutathione S-transferase (GST) and levels of glutathione (GSH)
      and NO* were increased with radiation dose up to 4Gy. Ca2+ augmented the
      radiation-induced responses. The presence of ionophore A23187 potentiated the
      modulatory effects of Ca2+. CONCLUSIONS: These findings show that Ca2+ augments
      radiation damage and is more effective intracellularly. Ca2+, peroxidation,
      cellular damage and apoptosis are possibly interlinked through signals, as is
      evident from the increased activity of NF-kappaB and generation of NO*. The
      enhanced antioxidant status suggests an attempt made by the irradiated cells to
      maintain their normal functions.

PMID- 14703947
TI  - Effect of expression of the Escherichia coli nth gene in Saccharomyces cerevisiae
      on the toxicity of ionizing radiation and hydrogen peroxide.
AB  - PURPOSE: To examine the contribution of endonuclease III (Nth)-repairable lesions
      to the cytotoxicity of ionizing radiation (IR) and hydrogen peroxide (H2O2) in
      the yeast Saccharomyces cerevisiae. MATERIALS AND METHODS: A selectable
      expression vector containing the E. coli nth gene was transformed into two
      different wild-type strains (7799-4B and YNN-27) as well as one rad52 mutant
      strain (C5-6). Nth expression was verified by Western analysis. Colony-forming
      assay was used to determine the sensitivity to IR and H2O2 in both stationary and
      exponentially growing cells. RESULTS: The pADHnth-transformed wild-type (77994B)
      strain was considerably more resistant than vector-only transformants to the
      toxic effects of IR, in both stationary and exponential growth phases, although
      this was not the case in another wild-type strain (YNN-27). In contrast, there
      were no significant effects of nth expression on the sensitivity of the wild-type
      cells to H2O2. Moreover, nth expression caused no effects on the H2O2 sensitivity
      in the rad52 mutant cells, but it led to a slight increase in sensitivity in
      these cells following IR, particularly at the highest dose levels used.
      CONCLUSIONS: Whilst other damage-processing systems may play a role, DNA lesions
      that are substrates for Nth can also make a contribution to the toxic effects of
      IR in certain wild-type yeast. Hence, DNA double-strand breaks should not be
      considered the sole lethal lesions following IR exposure.

PMID- 14703948
TI  - Review of acarbose therapeutic strategies in the long-term treatment and in the
      prevention of type 2 diabetes.
AB  - Acarbose--the most extensively investigated and widely prescribed alpha
      glucosidase inhibitor--reduces postprandial plasma glucose excursions by delaying
      the absorption of carbohydrate from the small intestine. Acarbose is an effective
      first-line therapy for patients with newly diagnosed type 2 diabetes, and induces
      a further improvement in glycemic control when used in combination with other
      antidiabetes agents. By decreasing postprandial hyperglycemia and improving
      insulin sensitivity, acarbose therapy also reduces fasting and postprandial serum
      insulin, fasting plasma glucose, and hemoglobin A1c levels. As the burden of type
      2 diabetes continues to grow, there is a great need for an oral antidiabetes
      agent with a proven ability to prevent the development of micro- and
      macrovascular complications, and maintain long-term glycemic control. More than
      15 years of clinical investigation have confirmed the sustained efficacy,
      tolerability, and excellent safety profile of acarbose in a wide range of patient
      types. Furthermore, the results of the recent Study to Prevent Non-Insulin
      Dependent Diabetes Mellitus (STOP-NIDDM) showed that acarbose therapy
      significantly decreased the risk of cardiovascular events in high-risk
      individuals with glucose intolerance. Acarbose is therefore a convenient and
      effective long-term option for the treatment of type 2 diabetes, with the added
      benefit of reducing cardiovascular risk.

PMID- 14703949
TI  - First clinical trial of a novel caspase inhibitor: anti-apoptotic caspase
      inhibitor, IDN-6556, improves liver enzymes.
AB  - OBJECTIVE: To evaluate the safety of IDN-6556, a novel anti-apoptotic pan-caspase
      inhibitor, administered in single and multiple ascending doses in normal
      volunteers and patients with hepatic dysfunction. MATERIALS AND METHODS: IDN-6556
      was administered as a 30-minute intravenous infusion in rising doses to 3 groups:
      Group A, normal volunteers, given as a single infusion, Group B, normal
      volunteers, given q.i.d. for 7 days, Group C, patients with hepatic impairment
      (elevated transaminases, alanine transaminase, ALT and aspartate transaminase,
      AST), given q.i.d. for 7 days. RESULTS: The drug was well tolerated up to 10
      mg/kg/infusion for a single dose, and 1.5 mg/kg/infusion q.i.d. for 7 days, with
      the dose-limiting adverse event of phlebitis or inflammation at the site of the
      infusion. This toxicity was predicted from animal studies. Clinically and
      statistically meaningful dose-related falls in transaminases were seen in all but
      1 of the hepatic impaired patients. Two-way ANOVA analyses of the changes for all
      the IDN-6556 groups combined versus placebo were: ALT absolute change: p < 0.0001
      and % change: p = 0.012, AST absolute and % changes: p < 0.0001. After
      discontinuation of the drug (after 7 days of dosing), the transaminases rapidly
      returned to the pre-treatment levels. CONCLUSIONS: Following intravenous
      administration of a novel anti-apoptotic caspase inhibitor, adverse events were
      mild-to-moderate in severity, resolved in a few days and did not result in any
      subject terminating treatment prematurely. The effects in hepatic impaired
      patients appear to be consistent with both the administration and subsequent
      abrupt withdrawal of an effective hepatoprotective drug that delays cell death in
      hepatocytes.

PMID- 14703950
TI  - Dose individualization in PharmDIS-e+.
AB  - Individualized dosage regimen calculations require knowledge on the
      pharmacokinetic and pharmacodynamic properties of the drug and the
      characteristics of the patient. A PK-PD-based dosage regimen is not easily and
      generally applicable, mainly because the combination of available PK parameters
      and therapeutic target levels may be inappropriate for the purpose of predicting
      a plausible dosage regimen. Within the project PharmDIS-e+, an alternative
      approach was chosen, and this "PK and standard dose"-based principle is well
      suited for computerized dosing advice. PharmDIS-e+ aims at the development of
      several applications for dosing regimen advice for general practitioners,
      hospital physicians and pharmacists.

PMID- 14703951
TI  - Proinflammatory blood monocytes: main effector and target cells in systemic and
      renal disease; background and therapeutic implications.
AB  - Although peripheral blood monocytes are heterogeneous, they all express the CD14
      molecule, a multifunctional receptor, and part of the toll-like membrane receptor
      complex. In healthy persons, a minor subset (8%) coexpresses CD14 and CD16, a low
      affinity Fc-gamma type III receptor. This subpopulation shows characteristics of
      tissue macrophages and expands greatly in acute and chronic infections, systemic
      inflammatory syndromes, hyperlipidedemia, AIDS and renal failure. CD14+/CD16+
      monocytes (Mo) exhibit higher phagocytosis activity than CD14++/CD16-negative
      monocytes and synthesize high levels of interleukin-1, TNF-alpha and HLA-DR, -DP
      and -DQ antigens. Glucocorticoids (and interleukin-4), and successful therapy in
      patients with inflammatory and septic complications lead to a down-regulation in
      the expression of CD14 and deplete CD14+/CD16+-proinflammatory Mo. Recovery of
      low monocytic HLA-DR expression parallels clinical improvement. Serial analyses
      of Mo phenotypes may be useful tools for monitoring patients receiving
      immunosuppressive and anti-inflammatory therapy respectively.

PMID- 14703952
TI  - Review of the antiproliferative properties of mycophenolate mofetil in non-immune
      cells.
AB  - Mycophenolate mofetil (MMF), the prodrug ofmycophenolic acid (MPA), is a
      selective, non-competitive and reversible inhibitor of inosine monophosphate
      dehydrogenase (IMPDH) and of the type II isoform in particular. IMPDH is the rate
      limiting enzyme in the de novo biosynthesis of guanosine nucleotides. MMF
      strongly inhibits both T- and B lymphocyte proliferation and has been used in the
      prevention of acute and chronic allograft rejection since the mid 1990s. Recent
      evidence, however, suggests that MMF is also capable of inhibiting the
      proliferation of non-immune cells. In various cell lines, i.e. smooth muscle
      cells, renal tubular cells and mesangial cells, MPA reduced or even abrogated
      proliferation in response to proliferative stimuli. Furthermore, data from our
      own laboratory demonstrate a dose-dependent inhibition of dermal fibroblast
      proliferation by MPA. In animal studies, MMF ameliorated renal lesions in immune
      mediated disease, i.e. in the anti-thy 1.1 model and experimental lupus
      nephritis, but was also effective in non-immune-mediated renal damage in the rat
      remnant-kidney model. These observations prompted several investigators to study
      the effects of MMF in proliferating (renal) disease of non-immune origin in
      humans. MMF significantly reduced proteinuria in minimal-change disease and focal
      segmental glomerulosclerosis. In addition, MMF showed beneficial effects in the
      treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity
      through reduction of immune- and non-immune-mediated renal damage. MMF is well
      tolerated and has proven to be a relatively safe drug causing only minor bone
      marrow suppression. Taken together, there is a growing body of evidence pointing
      to therapeutic applications of MMF other than immunosuppression, in particular
      the prevention of fibrosis.

PMID- 14703953
TI  - Effect of mycophenolate mofetil on IMP dehydrogenase after the first dose and
      after long-term treatment in renal transplant recipients.
AB  - OBJECTIVE: Mycophenolate mofetil (MMF) is routinely used as an immunosuppressant
      in a fixed daily dose regimen although it shows marked fluctuations in
      pharmacokinetics, and despite the fact that in regard to the active metabolite,
      mycophenolic acid (MPA), there is a well-known association between the
      pharmacokinetic parameters and clinical outcome. METHOD: In order to determine
      the time course and the variability in cellular target of MPA after renal
      transplantation, we investigated the pharmacodynamic response in 8 patients
      receiving 1 g MMF for the first time prior to renal transplantation and in 8
      stable renal transplant patients maintained on long-term MMF therapy (1 g b.i.d.)
      for more than 1 year. The pharmacodynamic response was measured using inosine 5'
      monophosphate dehydrogenase (IMPDH) activity in peripheral mononuclear cells. MPA
      plasma concentrations were measured in parallel, IMPDH activity in 89 healthy
      blood donors was used as a control. RESULTS: We observed a high interindividual
      variability in IMPDH activity in the 89 untreated healthy volunteers (4.0 - 32.9
      nmol/h/mg protein), in 8 patients on dialysis (5.3 - 18.9 nmol/h/mg protein) and
      in 8 renal transplant patients under long-term MMF treatment (2.3 - 14.4
      nmol/h/mg protein). The mean AUC0-12h for mycophenolic acid was 2-fold higher in
      patients receiving long-term treatment with MMF (62.2 +/- 16.6 mg x h/ml)
      compared to dialysis patients receiving 1 g MMF for the first time (31.5 +/- 15.6
      mg x h/ml). Despite this pharmacokinetic difference there were no statistically
      significant differences in the cellular pharmacodynamic response. Minimal IMPDH
      activity (1.62 +/- 1.23 vs. 1.77 +/- 1.49 nmol/h/mg protein) and maximal IMPDH
      inhibition (87.5 +/- 0.08 vs. 77.4 +/- 18.8%) during the dosing interval were
      similar. CONCLUSIONS: The considerable interindividual variability in the
      pharmacokinetics of MMF as well as in the drug target support the use of
      pharmacodynamic drug monitoring to optimize MMF dosing and to reduce the risk of
      graft rejection and side effects.

PMID- 14703954
TI  - Cyclosporin C2hour monitoring after renal transplantation.
AB  - Therapeutic drug monitoring of cyclosporin A (CsA) is essential because of its
      variable pharmacokinetics in individual patients and its narrow therapeutic
      window. In the past, standard trough level (C0) monitoring has been used, and
      although this method is currently the routine strategy, it has been shown that a
      single blood concentration measurement 2 hours after CsA administration (C2hour)
      is a significantly more accurate predictor of drug exposure and clinical events
      than trough concentrations. The CsA absorption profiling, in particular the
      measurement of C2hour, is a much more sensitive approach to assessing the
      pharmacokinetics and predicting the clinical effect in the individual patient.
      However, there are limited prospective data available examining the risks and
      benefits of C2hour monitoring in renal transplant recipients. Most studies focus
      on the early post-transplant phase, but there is little experience with C2hour
      monitoring in maintenance patients. Our experience in 127 stable long-term renal
      allograft recipients suggests that the therapeutic window for C2hour levels in
      patients during maintenance is lower than previously anticipated. Repeat
      determinations of both C0 and C2hour levels in 46 patients to determine precision
      of C2hour monitoring showed a high intrapatient variability. We observed only a
      slightly better coefficient of variation for C2hour than for C0 in repeat
      determinations. This suggests that drug monitoring using C2hour levels in
      transplant patients may provide a more accurate and reliable measure of drug
      exposure in the individual patient. However, CsA absorption showed only a weak
      correlation with dose during repeated measurements, suggesting high variability
      in absorption in these stable patients. We conclude that an adequate C2hour level
      soon after transplantation is associated with a reduced risk of acute rejection
      in adult renal transplant recipients. It is important to identify slow and poor
      absorbers in the initial phase after transplantation in order to avoid
      inappropriate increases in CsA dose. In maintenance patients, C2hour values
      between 500 and 600 ng/ml are effective and safe for providing effective
      rejection prophylaxis. Although mean C2hour levels do not seem to identify
      patients at risk of rejection, they may help to identify excessive
      immunosuppression and to improve long-term survival by reducing CsA toxicity.

PMID- 14703955
TI  - Pharmacodynamics of FTY720, the first member of a new class of immune-modulating
      therapeutics in transplantation medicine.
AB  - FTY is a novel immunomodulator currently undergoing clinical investigation and
      has the potential of improving immunosuppressive therapy after organ
      transplantation. Previous experimental studies in animals have shown that FTY has
      a unique mechanism of action. We have studied the pharmacodynamic effects of FTY
      in stable renal allograft recipients taking part in a phase I clinical trial. As
      in various animal models including non-human primates, a single oral dose of FTY
      (0.25 - 3.5 mg) significantly reduced peripheral lymphocyte count by 30 - 70%.
      The peripheral lymphocyte count returned to baseline within 24 hours. Only in
      those patients treated with the highest dose of FTY (3.5 mg), did peripheral
      lymphopenia persist for more than 96 hours. FTY reduced all lymphocyte subsets, T
      cells more than B cells and CD4+ cells more than CD8+ cells. The reduction in
      CD3+CD62L+ cell counts was more pronounced, whereas CD3+CCR5+ cell counts were
      less affected in comparison to the total number of CD3+ lymphocytes. We found
      only slightly increased apoptosis rates (< 5%) in peripheral lymphocytes, and
      this change does not explain the marked reduction in lymphocyte count. In
      cultured human lymphocytes only suprapharmacological doses of 10 microM FTY
      induced apoptosis (20.6 +/- 2.8%) after a 4-h incubation. More important,
      clinically relevant doses of 0.1 microM FTY increased lymphocyte mobility 2-fold.
      No effect of FTY on anti-CD3mAb-stimulated lymphocyte proliferation was detected
      and there was no change in phagocytosis rates in whole-blood cultures incubated
      with FTY. Further studies are necessary to investigate the mechanism of action of
      FTY in detail.

PMID- 14703956
TI  - Treating type 2 diabetes in renal insufficiency: the role of pioglitazone.
AB  - The advent of new antidiabetic drugs is of special importance for diabetic
      patients with already impaired renal function since renal insufficiency is a
      relative or absolute contraindication for several of the established hypoglycemic
      drugs. Pioglitazone is a novel oral hypoglycemic agent that increases insulin
      responsiveness in target tissues. Pioglitazone and its active metabolites are
      excreted mainly via the liver. Drug exposure remains almost constant across a
      wide range of renal function since there is no accumulation of the drug or its
      active metabolites during repeated dosing in renal insufficiency. The
      pharmacokinetic properties of pioglitazone are ideally suited for patients with
      renal insufficiency. Although there are possible side effects (mainly fluid
      retention and weight gain and--very rarely--hepatotoxicity). Pioglitazone has a
      good safety profile in diabetic patients with impaired renal function.

PMID- 14703957
TI  - Pharmacokinetics and pharmacodynamics of lispro-insulin in hemodialysis patients
      with diabetes mellitus.
AB  - OBJECTIVE: Lispro-insulin, after subcutaneous injection in patients with normal
      renal function, is absorbed faster and has a faster onset of action when compared
      to regular insulin. However, the pharmacokinetics and pharmacodynamics of lispro
      insulin in renal failure have not yet been investigated. PATIENTS AND METHODS:
      Eight patients with diabetes mellitus on long-term hemodialysis received an
      individualized dose of regular insulin or lispro-insulin in a crossover design.
      Blood glucose and insulin concentrations were measured before and after the
      subcutaneous insulin injections. RESULTS: Plasma insulin concentrations increased
      faster (time of maximum concentration tmax 20 vs 40 minutes, p = 0.01) and were
      higher (standardized maximum concentration Cmax/D 13.6 vs 6.1 microU/ml/U, p =
      0.01) after lispro-insulin compared to regular insulin. The area under the curve,
      clearance and parameters of the hypoglycemic action for the 2 insulin products
      did not differ significantly, but there was a trend to minimum blood glucose
      level (time of the blood glucose minimum, Gtmin) to occur earlier with lispro
      insulin (120 vs 210 minutes, p > 0.05). Differences in elimination half-life and
      volume of distribution were explained by flip-flop pharmacokinetics in the case
      of regular insulin. CONCLUSIONS: In hemodialysis patients with diabetes mellitus,
      lispro-insulin is absorbed faster than regular insulin. Differences in the
      effects of lispro-and regular insulin can be explained by the differences in
      pharmacokinetics.

PMID- 14703958
TI  - About the conformations of alpha,beta-diunsaturated ketones.
AB  - Substituted 1-(cyclohexenyl)-3-phenylpropen-1-ones, 1-(2-furyl)-3-phenylpropen-1
      ones, and 1-(2-thienyl)-3-phenylpropen-1-ones, ketones with 1,4-pentadien-3-one
      structure, prefer in solution, and at room temperature, according to 1H NMR and
      IR investigations the s-trans/s-cis conformation. For some compounds the
      participation of other conformers in the equilibrium could be demonstrated. These
      results were obtained by a qualitative study of 25 derivatives in different
      solvents, and comparison with results from MM+, PM3, AM1 or MMX calculations.

PMID- 14703959
TI  - Structure-activity relationships of novel anti-malarial agents part 8. Effect of
      different central aryls in biarylacryloylaminobenzophenones on antimalarial
      activity.
AB  - Replacement of the 2,5-disubstituted furyl residue present in the known
      antimalarial agents 8 by other aryl residues resulted in a more or less reduced
      antimalarial activity in most cases. The only exemption was the 2,4-thienylene
      compound 11a displaying activity with an IC50 value of 120 nM. In conclusion, the
      2,5-furylene compound 8e remains to represent the most active antimalarial agent
      in this series of farnesyltransferase inhibitors.

PMID- 14703960
TI  - Enzymatic synthesis of N-acetyllactosamine in aqueous-organic reaction media.
AB  - Beta-galactosidase from Bacillus circulans was used for the biocatalytic transfer
      of D-galactose (D-Gal) from o-nitrophenyl-beta-D-galactoside (ONPG) to the O-4
      position of 2-acetamido-2-deoxy-D-glucopyranose (D-GlcNAc) forming the
      disaccharide N-acetyllactosamine (LacNAc, beta-D-Gal-(1 --> 4)-D-GlcNAc). In
      order to investigate the potential of this biocatalytic synthesis, first the
      optimal reactant ratio in an aqueous buffer system was determined. On the basis
      of these standard conditions we then performed reactions in aqueous-organic media
      applying organic cosolvents of different structure and polarity in various
      amounts. In this way we received in some cases appreciably better results than
      without organic cosolvent. The highest obtainable disaccharide yield was 50% in a
      mixture of 20% (v/v) cyclohexane/80% buffer versus 35% in buffer solution alone.

PMID- 14703961
TI  - Reexamination of some reactions of 3-(D-galactosylidenehydrazino)-1,2,4
      triazino[5,6-b]indole.
AB  - Incorrect structures described in the literature for the products of reactions of
      the title compound 6 were reexamined and corrected. Thus, the product of
      acetylation of 6 with acetic anhydride in the presence of pyridine was found to
      be the mono-N-penta-O-acetyl derivative 10 and not the previously described di-N
      penta-O-acetyl derivative 7. Assignment of structure 10 was based on 1H NMR data
      as well as its ability to undergo oxidative cyclization with Br2/AcOH to give 12.
      The previously assigned structure 7 would be incapable of undergoing such
      cyclization. The linear structure 12 rather than the angular regioisomer 3c was
      assigned on the basis of its UV absorption pattern and 1H NMR NOE spectra.
      Attempted preparation of 7 by increasing the duration of the reaction gave only
      compound 10. A di-N-acetyl-penta-O-acetyl derivative, however, was obtained with
      acetyl bromide in the presence of pyridine to which structure 8 rather than
      structure 7 or 9 was assigned on the basis of 1H NMR NOE studies. Acetylation of
      the triazolo-triazino-indole 11 gave a product identical to 12; structure 15
      previously assigned to this product is, therefore, in error. Finally, the angular
      annelated structure 3e previously ascribed to the oxidative cyclization product
      of the 5-methylhydrazone congener of 6 (13) is now rectified to the linear
      annelated structure 14; the latter was found to be identical to the product
      obtained by N-methylation of the unequivocally linear 1,2,4-triazolo[4,3-b]1,2,4
      triazino[5,6-b]indole 11. Compound 8 was found to exist in the preponderantly
      populated sickle (bent) conformation 18 in contrast to compounds 10 and 12 which
      were found to adopt the extended planar zigzag conformations 19 and 20
      respectively.

PMID- 14703962
TI  - [Simultaneous photometric determination of covalently bound fluorine and fluoride
      ion contamination adsorbed on drugs in the low ppm range after alkaline pulping].
AB  - The simultaneous determination of fluorine resulting from inorganic fluoride as
      well as fluorine-containing solvents adsorbed to drugs was achieved in the 0.1-30
      ppm range by a combination of decomposition with magnesium oxide at 800 degrees C
      and steam distillation of the resulting fluoride followed by photometric
      measurement of the aminomethylalizarindiacetic acid-cerium(III) complex at 620
      nm. The inevitable loss of fluoride occurring during the decomposition and
      distillation processes was corrected using factors derived from authorized
      calibrations. The method was validated using glucose contaminated with
      dexamethasone which contains 4.84% fluorine per molecule.

PMID- 14703963
TI  - Voltammetric and HPLC determination of dorzolamide hydrochloride in eye drops.
AB  - The behaviour of dorzolamide hydrochloride (DOR) was investigated at a glassy
      carbon electrode in different buffer systems using cyclic (CV), linear sweep
      (LSV) and differential pulse voltammetry (DPV). The oxidation process was found
      to be irreversible over the pH range studied (2.0-8.0) and was shown to be
      diffusion controlled. An analytical method with adequate precision and accuracy
      was developed for the determination of DOR in Britton-Robinson buffer (BRb) at pH
      = 3.06 containing 10% methanol as supporting electrolyte. The peak current varied
      linearly with DOR concentration in the range 4.0 x 10(-5)-6.0 x 10(-4) M.
      Furthermore, a HPLC method with diode array detection was developed. A
      calibration graph was established for 1.1 x 10(-6)-1.9 x 10(-4) M of DOR. The
      procedures were successfully applied for the determination of the drug in eye
      drops.

PMID- 14703964
TI  - Spectrofluorometric determination of nimodipine in dosage forms and human urine.
AB  - A simple sensitive and specific spectrofluorometric method was developed for the
      determination of nimodipine (NDP) in pharmaceutical preparations and human urine.
      The method is based on reduction of nimodipine with Zn/HCl and measuring the
      obtained fluorescence at 425 nm after excitation at 360 nm. The factors affecting
      the development of the fluorophore and its stability were studied and optimized.
      The effect of some surfactants such as beta-cyclodextrin (betaCD),
      carboxymethylcelullose (CMC), sodium dodecyl sulphate (SDS) and Triton X-100, on
      the fluorescence intensity was studied. The fluorescence intensity-concentration
      plot is rectilinear over the range 0.1-5.0 microg/ml in presence of Triton X-100
      with a minimum detectability limit of 0.06 microg/ml (1.62 x 10(-7) M). The
      proposed method was successfully applied to commercial tablets containing NDP,
      the percentage recovery agreed well with those obtained using the official
      methods. The method was further extended to the in vitro determination of NDP in
      spiked human urine samples. The % recovery was 102.1 +/- 2.54 (n = 4). A proposal
      of the reduction reaction pathway was postulated.

PMID- 14703965
TI  - ICH guideline for photostability testing: aspects and directions for use.
AB  - The ICH guideline Q1B for photostability testing gives guidance on the basic
      testing protocol required to evaluate the light sensitivity and stability of new
      drugs and products. The choice of the irradiation method, although complying with
      the guideline demands, may effect test results. High irradiances may shorten
      testing times, but can lead to enforcement of photodegradation, which was
      demonstrated for molsidomine tablets. The exposure to an artificial light source
      (xenon lamp) was compared and correlated to natural daylight. Suitable testing
      methods for nifedipine and molsidomine tablets were developed. Deviating from the
      guideline recommendations, the presentation of powder samples should be done in
      tiny aluminium pans, facilitating the test procedure, minimising the risk of
      falsified test results due to improper sampling and improving reproducibility.
      When using glass dishes for the presentation of tablets to photostability
      testing, they should be lined by e. g. aluminium foil to avoid influences of
      light reflected from the sample tray.

PMID- 14703966
TI  - Stability testing on typical flavonoid containing herbal drugs.
AB  - The aim of the presented work was to examine possible changes in the flavonoid
      pattern of common flavonoid containing herbal drugs during long term and stress
      testing storage periods. HPLC fingerprint was used to demonstrate the differences
      in stability of individual flavonoid components. In addition, the total flavonoid
      content was determined according to the pharmacopoeial photometrical method. Drug
      material was stored according to the ICH-guidelines at 25 degrees C and 60% rh
      (relative humidity) for long term testing over a 24 months period or at 40
      degrees C and 75% rh under stress conditions for 6 months. Increased temperatures
      of 80 degrees C and 100 degrees C were chosen to elucidate possible instabilities
      of selected flavonoids. As an overall result, during long term testing, no
      significant changes in the flavonoid pattern can be detected. However, some
      flavonoid containing herbal drugs (e.g. birch leaves), showed a decrease of most
      flavonoids when stored at high temperature by an increase in the respective
      aglycones. Similar results were obtained during storage at 40 degrees C/75% rh.

PMID- 14703967
TI  - Influence of methacrylic acid and hydroxypropylmethyl cellulose on the tablet
      properties and in vitro release of dextromethorphan hydrobromide.
AB  - The release of dextromethorphan hydrobromide from matrices containing
      hydroxypropylmethyl cellulose (HPMC K100LV) and methacrylic acid copolymer
      (Eudragit L100-55) has been evaluated at different ratios of the polymers. The
      physicochemical properties (including weight, thickness, crushing strengh,
      friability and disintegration time) were also determined at 1000, 2000 and 4000 p
      compression forces. No significant differences in weight uniformity and thickness
      values were observed between the different formulations. The crushing strength of
      the tablets increased with increasing compression force and it reached a constant
      level at 4000 p. The formulations containing only HPMC K100LV resulted in an
      extended release pattern, however, Eudragit L100-55 alone could not effectively
      prolong the drug release. A combination of HPMC K100LV and Eudragit L100-55 in a
      1:1 ratio at the 40% level provided an almost similar drug release profile than
      the marketed product.

PMID- 14703968
TI  - Effect of some penetration enhancers on the permeation of glibenclamide and
      glipizide through mouse skin.
AB  - The purpose of this investigation was to study the effect of some penetration
      enhancers on in vitro permeation of glibenclamide and glipizide through mouse
      skin. Ethanol in various concentrations, N-methyl-2-pyrrolidinone, transcutol,
      propylene glycol and terpenes like citral, geraniol and eugenol were used as
      penetration enhancers. The in vitro skin permeation experiments were conducted by
      both simultaneous application of drug and enhancer solution and by pretreatment
      of the skin with neat enhancer. At the end of the experiment drug retained in the
      skin was estimated. The flux values (microg/cm2/h) of both drugs significantly (p
      < 0.05) increased in the presence of penetration enhancers, except transcutol and
      propylene glycol. The glibenclamide flux values ranged from 1.42 +/- 0.09 without
      enhancer, to 18.25 +/- 1.21 in a combination of 50% ethanol and 5% eugenol.
      Glipizide flux values ranged from 3.21 +/- 0.51 without enhancer, to 57.21 +/-
      5.25 in a combination of 50% ethanol and 5% eugenol. Skin retention and
      solubility of both drugs increased with all penetration enhancers compared to
      control (except propylene glycol). As the target permeation rates for
      glibenclamide and glipizide were calculated to be 193.8 and 184.8 microg/h
      respectively, the present study showed that the required permeation rates for
      both drugs could be achieved with the aid of enhancers by increasing the area of
      application in an appreciable range.

PMID- 14703969
TI  - Combination strategies to enhance transdermal permeation of zidovudine (AZT).
AB  - The objective of this study was to evaluate the effect of simultaneous
      application of two penetration enhancers of different chemical classes or a
      chemical penetration enhancer and current application on permeation of zidovudine
      (AZT) across rat skin. Ex vivo permeation of AZT using combinations of cineole or
      menthol in vehicle with either oleic acid/linolenic acid or 0.5 mA/cm2 anodal
      current application for 6 h was studied. Penetration enhancers were significantly
      different in enhancing the permeability of AZT across rat skin and are in the
      decreasing order of activity: linolenic acid > menthol > oleic acid > cineole >
      vehicle. The combination of cineole and oleic acid synergistically enhanced
      transdermal flux of AZT in addition to reducing lag time. However, this was not
      observed for combinations of menthol with oleic or linolenic acid. On the other
      hand, the simultaneous application of current with menthol and cineole
      significantly increased cumulative amounts of AZT permeating during the course of
      current application and reduced the lag time but failed to further increase
      steady state flux of AZT. These results suggest that a combination of two
      penetration enhancers of different classes or the simultaneous use of
      iontophoresis and a penetration enhancer may be advantageous to achieve
      permeation enhancement with low risk of skin damage.

PMID- 14703970
TI  - Evaluation of some aroxyethylamine derivatives for hypotensive properties and
      their affinities for adrenergic receptors.
AB  - A series of aroxyethylamines (1-10) was synthesized and evaluated for hypotensive
      activity in rats after intravenous and oral administration. The 4 compounds (4,
      7, 8 and 10) containing a (2-methoxy)phenylpiperazine moiety displayed
      hypotensive activity and their affinities for alpha1-, alpha2- and beta1
      adrenoreceptors were determined by radioligand binding assays. Compounds 4, 7, 8
      and 10 were also tested for their effect on the pressor responses to epinephrine,
      norepinephrine, methoxamine, tyramine and DMPP. The results suggest that the
      hypotensive effect of these compounds is related to their alpha- and beta
      adrenolytic properties.

PMID- 14703971
TI  - Studies on the involvement of bradykinin using enalapril and 2-mercaptoethanol in
      ischemia-reperfusion induced myocardial infarction in albino rats.
AB  - The effects of bradykinin were evaluated using the ACE inhibitor enalapril and
      the APP inhibitor, 2-mercaptoethanol alone and in combination in rats with
      experimental myocardial infarction. Myocardial infarction was produced by
      occlusion of the left anterior descending coronary artery for 30 min followed by
      4 h of reperfusion. Infarct size was measured by the TTC stain method. Lipid
      peroxide levels in serum and heart tissue were estimated by the methods developed
      by Yagi and Ohkawa et al., respectively. A lead II electrocardiogram was
      monitored throughout the experiment. With the combined inhibition of both the
      enzymes ACE and APP, a better cardioprotection was observed when compared to
      individual inhibition of the enzymes, suggesting the involvement of bradykinin
      during experimental myocardial infarction.

PMID- 14703972
TI  - Diadenosine tetraphosphate (Ap4A) induces a diabetogenic situation: its impact on
      blood glucose, plasma insulin, gluconeogenesis, glucose uptake and GLUT-4
      transporters.
AB  - Diadenosine polyphosphates such as Ap4A are physiologically released compounds
      for which both receptors as well as a role as second messengers for influencing
      insulin release have been shown. So far little is known about their
      pathophysiological impact on diabetes with respect to blood glucose and plasma
      insulin, glucose production via gluconeogenesis, glucose uptake and GLUT-4
      expression. Rats given an intravenous bolus of Ap4A (0.75 mg/kg) developed a
      rapid and dramatic increase in blood glucose. Plasma insulin was only transiently
      increased (for 4 min), but did not follow the normally stimulatory effect of the
      elevated blood glucose. A bolus of 25 microg Ap4A quickly increased glucose
      release from perfused rat liver. Glucose uptake was reduced in 3T3 adipocytes.
      Reduced amounts of translocated GLUT-4 were found in 3T3 cell membranes incubated
      with 10 microM Ap4A. Thus, Ap4A itself induces a diabetic situation which is
      likely to be mediated by an increase in gluconeogenesis and/or an insulin
      resistance caused by a decrease in GLUT-4 and an attenuation of glucose uptake.

PMID- 14703973
TI  - Effect of an aqueous extract of Phaseolus vulgaris on plasma insulin and hepatic
      key enzymes of glucose metabolism in experimental diabetes.
AB  - Oral administration of 200 mg/kg of aqueous extract of Phaseolus vulgaris pods
      (PPEt) to diabetic animals for 45 days resulted in a significant decrease in
      blood glucose, glycosylated haemoglobin and significant increase in total
      haemoglobin and plasma insulin. Similarly oral administration of PPEt to normal
      animals resulted in a significant hypoglycemic effect. The activities of hepatic
      hexokinase, glucose 6-phosphatase, fructose-1,6-bisphosphatase and glucose-6
      phosphate dehydrogenase, a lipogenic enzyme, were measured in the liver of normal
      and experimental animals. The activities of the lipogenic enzyme and hexokinase
      were significantly decreased, whereas the activities of gluconeogenic enzymes
      were significantly increased in the diabetic liver. Both PPEt and glibenclamide
      reversed the activities of these enzymes to near normal levels. PPEt was more
      effective than glibenclamide. The results indicate that the administration of
      PPEt to diabetic animals normalizes blood glucose and causes a marked improvement
      of altered carbohydrate metabolic enzymes during diabetes.

PMID- 14703974
TI  - Erythrocyte redox status in streptozotocin diabetic rats: effect of Casearia
      esculenta root extract.
AB  - The present study was aimed to investigate the effect of Casearia esculenta root
      extract on erythrocyte lipid peroxidation and to assess the status of
      antioxidants in red blood cells of streptozotocin (STZ) diabetic rats. The study
      showed a significant elevation (p < 0.05) of erythrocyte thiobarbituric acid
      reactive substances (TBARS), an index of lipid peroxidation and significant
      reduction (p < 0.05) in reduced glutathione (GSH), ascorbic acid (vitamin C),
      alpha-tocopherol (vitamin E), superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx) in the STZ diabetic rats. The study also observed
      significant reduction in membrane cholesterol and phospholipid content in STZ
      diabetic rats. By oral administration of C. esculenta (200 and 300 mg/kg body
      wt.) for 45 days to the diabetic rats these values approached almost normal
      levels. A dose of 300 mg/kg body weight C. esculenta extract showed better
      antioxidant effects than 200 mg/kg body weight.

PMID- 14703975
TI  - Osteoblastic differentiation bioassay and its application to investigating the
      activity of fractions and compounds from Psoralea corylifolia L.
AB  - A cell differentiation bioassay measuring alkaline phosphatase activity was
      developed using osteoblast-like UMR 106 cell line as a model. The effect of
      fractions and compounds of Psoralea corylifolia L. extract on osteoblastic
      differentiation was investigated. The fractions or compounds were co-cultured
      with cells for 48 h, the cellular ALP activity was then measured. The crude
      ethanol extract of Psoralea corylifolia L. increased ALP activity by 39.5% at a
      concentration of 0.1 mg/ml, and the activity was concentrated in the ethyl
      acetate fraction, which produced a maximum ALP activity increase of 38.2%. A
      significant activity was observed for a flavonoid, corylin, providing 30.0%
      increment in ALP. These effects suggest that Psoralea corylifolia L. extract, its
      ethyl acetate fraction and corylin would stimulate bone formation.

PMID- 14703976
TI  - Effectiveness of Aloe vera on the antioxidant status of different tissues in
      irradiated rats.
AB  - This study was performed to evaluate the role of Aloe vera (Aloe barbadensis
      Miller) on the antioxidant status in different tissues of animals whole body
      exposed to 7 Gy gamma radiations, delivered as a shot dose. Aloe vera (leaf juice
      filtrate) was supplemented daily to rats (0.25 ml/kg body weight/day), by gavage,
      5 days before irradiation and 10 days after irradiation. Experimental
      investigations performed 3, 7 and 10 days after exposure to radiation showed that
      Aloe vera treatment has significantly minimized the radiation-induced increase in
      the amount of malondialdehyde in liver, lungs, and kidney tissues of irradiated
      rats. Significant amelioration in superoxide dismutase (SOD) and catalase
      activities was observed from the 3rd up to the 10th days for lungs, on the 7th
      and 10th days for kidneys and at 10 days for liver. Data obtained showed that for
      the different tissues, improvement in the decrease of reduced glutathione (GSH)
      contents was obvious on the 10th day after irradiation. Treatment with Aloe vera
      was also effective in minimizing the radiation-induced increase in plasma glucose
      levels throughout the experimental period, while it has not ameliorated the
      increase in plasma insulin levels. It could be concluded that the synergistic
      relationship between the elements found in the leaf of Aloe vera could be a
      useful adjunct for maintaining the integrity of the antioxidant status.

PMID- 14703977
TI  - A novel naphthanol glycoside from Terminalia arjuna with antioxidant and nitric
      oxide inhibitory activities.
AB  - A novel naphthanol glycoside, arjunaphthanoloside (1), was isolated from the stem
      bark of Terminalia arjuna and its structure was established as 2,3,6,7,8,9
      hexahydroxynaphthalene-2-O-alpha-L(-)-rhamnoside by means of spectroscopic and
      chemical methods. Compound 1 showed potent antioxidant activity and inhibited
      nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated rat
      peritoneal macrophages.

PMID- 14703978
TI  - Galanthamine distribution in Bulgarian Galanthus spp.
AB  - Sixteen populations of Galanthus elwesii Hook.fil and five populations of
      Galanthus nivalis L. growing in Bulgaria were investigated for the presence of
      galanthamine by TLC and GC-MS. Between 3 and 11 alkaloids were detected by TLC in
      the total alkaloid fractions. Galanthamine was found in 2 populations of G.
      elwesii.

PMID- 14703979
TI  - Lupane triterpenoids from Salvia roborowskii Maxim.
AB  - A new lupane type triterpenoid, 3beta, 11alpha-dihydroxy-30-norlupan-20-one and 6
      known lupane triterpenoids were isolated from the petroleum ether (60-90 degrees
      C) extract of the whole plant of Salvia roborowskii Maxim. Their structures were
      elucidated by means of spectral methods including NMR and MS techniques.

PMID- 14703980
TI  - Enzymatic reaction in multiple w/o/w emulsions: effect of the nature of the
      lipophilic phase.

PMID- 14703981
TI  - Three new butyl glycosides from Inula crithmoides L. growing in Egypt.

PMID- 14703982
TI  - Proteolytic sensitivity of a recombinant phospholipase D from cabbage:
      identification of loop regions and conformational changes.
AB  - A recombinant phospholipase D from white cabbage (PLD2) composed of 812 amino
      acid residues was studied by site-directed mutagenesis and limited proteolysis to
      obtain first information on its tertiary structure. Limited proteolysis by
      thermolysin resulted in the formation of some large fragments of PLD2. From mass
      spectrometry and N-terminal sequencing of the peptides, the cleavage sites could
      be identified (1. Thr41-Ile42, 2. Asn323-Leu324 or Gly287-Leu288 and Ser319
      Ile320 in case of the mutant L324S-PLD2). This suggested an exposed loop in the
      C2 domain of PLD2 and a large flexible region close to the N-terminal side of the
      first catalytic (HKD) motif. Calcium ions, the substrate 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine and the competitive inhibitor 1,3-dipalmitoylglycero-2
      phosphocholine influenced the proteolytic cleavage. Calcium ions exerted a
      destabilizing effect on the conformation of PLD2.

PMID- 14703983
TI  - Kinetic analysis of the binding of hemopexin-like domain of gelatinase B cloned
      and expressed in Pichia pastoris to tissue inhibitor of metalloproteinases-1.
AB  - The gelatinases are a subgroup of the matrix metalloproteinase family. The
      interaction of their C-terminal hemopexin-like domain with a tissue inhibitor of
      metalloproteinases (TIMP) is a major part of the regulatory mechanisms of
      gelatinases. To investigate the interaction of the hemopexin-like domain of
      gelatinase B (92-Pex) and TIMP-1, we expressed the individual domain in Pichia
      pastoris. The active refolded domain was purified by ion exchange chromatography
      and gel filtration. We investigated the formation of the 92-Pex/TIMP-1 complex by
      surface plasmon resonance (SPR). The dissociation constant Kd was calculated to
      be 0.86 nM. Analogous to the complex of the hemopexin-like domain of gelatinase A
      and TIMP-2 (Olson, M. W. et al., 1997), the binding curves of the 92-Pex/TIMP-1
      complex were best fitted with a monophasic model.

PMID- 14703984
TI  - Anaerobiospirillum succiniciproducens phosphoenolpyruvate carboxykinase:
      mutagenesis at metal site 2.
AB  - Phosphoenolpyruvate (PEP) carboxykinases harbor two divalent metal-binding sites.
      One cation interacts with the enzyme (metal binding site 1) to elicit activation,
      while a second cation (metal binding site 2) interacts with the nucleotide to
      serve as the metal nucleotide substrate. Mutants of Anaerobiospirillum
      succiniciproducens PEP carboxykinase have been constructed where Thr249 and
      Asp262, two residues of metal binding site 2 of the enzyme, were altered. Binding
      of the 3'(2')-O-(N-methylantraniloyl) derivative of ADP provides a test of the
      structural integrity of these mutants. The conservative mutation (Asp262Glu)
      retains a significant proportion of the wild type enzymatic activity. Meanwhile,
      removal of the OH group of Thr249 in the Thr249Ala mutant causes a decrease in
      V(max) by a factor of 1.1 x 10(4). Molecular modeling of wild type and mutant
      enzymes suggests that the lower catalytic efficiency of the Thr249Ala enzyme
      could be explained by a movement of the lateral chain of Lys248, a critical
      catalytic residue, away from the reaction center.

PMID- 14703985
TI  - Changes in glycation of fibrous type I collagen during long-term in vitro
      incubation with glucose.
AB  - The course of glycation of calf skin fibrous type I collagen was monitored in
      vitro under physiological conditions during an 8-week incubation period in order
      to take into account the long half-life of this protein. The formation of
      glycated compounds was measured by determining fructosamine, pentosidine, and
      carboxymethyllysine content. The incubation conditions were as physiological as
      possible in sterile saline phosphate buffer, except glucose concentration. With
      incubation medium containing 200 mmol glucose, fibrous collagen underwent
      solubilization; in addition an increase in fructosamine, pentosidine, and
      carboxymethyllysine content in both solubilized and remaining insoluble collagen
      was noticed. There was a spontaneous, restricted, and time-dependent native
      glycated state of collagen; high concentration glucose enhanced the formation of
      glycated compounds and induced changes in solubility and glycoxidated products.
      The production of pentosidine during incubation without glucose should be
      considered as an event resulting from the initial fructosamine. Whereas the
      production of carboxymethyllysine during long-term incubation with glucose
      provided indirect proof of an additional oxidative process after early glycated
      product formation. These experimental observations provide insight into the in
      vivo context of advanced glycation end product formation in chronic hyperglycemia
      and aging.

PMID- 14703986
TI  - In vitro glycoxidation of insoluble fibrous type I collagen: solubilization and
      advanced glycation end products.
AB  - The deleterious effects of glycoxidation are dependent on the half-life of
      proteins. Collagen, the main component of extracellular matrices, is a long live
      protein and thus may be sensitive to the glycoxidation process. We incubated calf
      skin fibrous type I collagen in PBS at 37 degrees C with glucose. The fibrous
      type I collagen was solubilized and an increase in the amount of advanced
      glycation end products of the solubilized fraction was observed. As there was no
      bacterial contamination and no proteolytic activities in the incubation medium,
      the solubilization of fibrous type I collagen is probably due to the speculative
      production of the free radicals in our experimental conditions. To test this
      hypothesis, fibrous type I collagen was incubated in PBS with AAPH (2,2'azo-bis 2
      aminodinopropane) a free radicals generator. AAPH induced a dramatic and dose
      dependent solubilization of fibrous type I collagen.

PMID- 14703987
TI  - Mapping of human plasma kallikrein active site by design of peptides based on
      modifications of a Kazal-type inhibitor reactive site.
AB  - Human plasma kallikrein (huPK) is a proteinase that participates in several
      biological processes. Although various inhibitors control its activity, members
      of the Kazal family have not been identified as huPK inhibitors. In order to map
      the enzyme active site, we synthesized peptides based on the reactive site
      (PRILSPV) of a natural Kazal-type inhibitor found in Cayman plasma, which is not
      an huPK inhibitor. As expected, the leader peptide (Abz-SAPRILSPVQ-EDDnp) was not
      cleaved by huPK. Modifications to the leader peptide at P'1, P'3 and P'4
      positions were made according to the sequence of a phage display-generated
      recombinant Kazal inhibitor (PYTLKWV) that presented huPK-binding ability. Novel
      peptides were identified as substrates for huPK and related enzymes. Both porcine
      pancreatic and human plasma kallikreins cleaved peptides at Arg or Lys bonds,
      whereas human pancreatic kallikrein cleaved bonds involving Arg or a pair of
      hydrophobic amino acid residues. Peptide hydrolysis by pancreatic kallikrein was
      not significantly altered by amino acid replacements. The peptide Abz-SAPRILSWVQ
      EDDnp was the best substrate and a competitive inhibitor for huPK, indicating
      that Trp residue at the P'4 position is important for enzyme action.

PMID- 14703988
TI  - Characterization of a proteinase inhibitor from Cajanus cajan (L.).
AB  - A protein proteinase inhibitor (PI) has been purified from pigeonpea Cajanus
      cajan (L.) PUSA 33 variety by acetic-acid precipitation, salt fractionation and
      chromatography on a DEAE-Cellulose column. The content of inhibitor was found to
      be 15 mg/20 g dry weight of pulse. The molecular weight of the inhibitor as
      determined by SDS-PAGE under reducing conditions was found to be about 14,000. It
      showed inhibitory activity toward proteolytic enzymes belonging to the serine
      protease group, namely trypsin and alpha-chymotrypsin. The inhibitory activity
      was stable over a wide range of pH and temperatures. Estimation of sulfhydryl
      groups yielded one free cysteine and at least two disulfide linkages. N-terminal
      sequence homology suggests that it belongs to the Kunitz inhibitor family.
      Structural analysis by circular dichroism shows that the inhibitor possesses a
      largely disordered structure.

PMID- 14703989
TI  - Differences in the average single molecule activities of E. coli beta
      galactosidase: effect of source, enzyme molecule age and temperature of
      induction.
AB  - Using a capillary electrophoresis-based method, single enzyme molecule assays
      were performed on E. coli beta-galactosidase from three different sets of
      samples. The first set consisted of lysates of induced cells from five different
      strains of the bacteria, as well as two different commercial preparations of the
      enzyme. These samples were found to have substantially different distributions of
      single molecule activities. For the second set of samples, beta-galactosidase
      expression was induced for 1.5 hr, followed by further incubation where
      expression was repressed. Assays were performed on the lysates of the
      preinduction and on the lysates from aliquots taken set times postinduction. The
      recently induced enzyme had a 25% higher average single molecule activity than
      the basally expressed enzyme. This average activity returned to the basal value
      3.5 hr postinduction and remained unchanged thereafter. Finally, beta
      galactosidase was induced at 26 and 42 degrees C. The enzyme was assayed before
      and after partial thermal denaturation. The samples were found to be
      indistinguishable with respect to their average single molecule activities.

PMID- 14703990
TI  - Aggregation and folding of recombinant human creatine kinase.
AB  - The processes of aggregation and refolding of recombinant human creatine kinase
      (rHCK) were studied. Most of the rHCK expressed in E. coli was present in the
      insoluble traction and it could be solubilized in 6 M urea solution. Unfolding of
      rHCK in 6 M urea showed biphasic kinetic courses (kappa1 = 6.5 x 10(-3) s(-1);
      kappa2 = 0.54 x 10(-3) s(-1)) as observed by maximum fluorescence wavelength
      change. During refolding of the rHCK dissolved in urea, significant aggregation
      was noticed following first-order kinetics. Aggregation rate constants were
      influenced by the concentration of NaCl, which increased the difference in
      transition-free energy (deltadeltaG), showing that stabilization of folding
      intermediates by NaCl could efficiently reduce the formation of insoluble
      aggregates. Formations of aggregate were also reduced by adjusting temperature,
      pH, and concentration of rHCK. Refolding of rHCK under the optimized condition
      which prevented the aggregation also showed multi-kinetic phases (kappa1 = 3.0 x
      10(-3) s(-1); kappa2 = 0.64 x 10(-3) s(-1)). Under optimized conditions applied
      in this study, rHCK could correctly refold retrieving the high specific enzymatic
      activity.

PMID- 14703991
TI  - Purification and characterization of Mr 43,000 protein similar to Mr 25,000
      protein, a substrate for protein Ser/Thr kinases, identified as a part of Xenopus
      laevis vitellogenin B1.
AB  - Mr 25,000 protein (pp25), a substrate for protein Ser/Thr kinases, was recently
      shown to consist of a portion of the Xenopus laevis vitellogenin B1 protein. By
      Western blot analyses using antibodies against pp25, a minor protein band with Mr
      43,000 (pp43) was detected in purified preparations of pp25. In this study, pp43
      was highly purified through several column chromatography steps and its protein
      structure was analyzed. The amino acid sequence of the amino-terminal region of
      pp43 was the same as that of pp25. pp43 contained about two times more phosphates
      than pp25. These phosphates in pp43 were more resistant to acid phosphatase
      attack than those of pp25. pp43 was able to bind to pNiXa, a binding protein of
      pp25. Alpha-chymotryptic digestion generated a common fragment with molecular
      mass of 23,000 from both pp43 and pp25. These results suggest that pp43 may be a
      precursor of pp25 generated during processing of vitellogenin B1.

PMID- 14703992
TI  - The effects of Ni2+, Co2+, and Mn2+ on human serum butyrylcholinesterase.
AB  - The effects of Ni2+, Co2+, and Mn2+ on human serum butyrylcholinesterase (BChE,
      acylcholine acylhydrolase E.C. 3.1.1.8) were investigated in this study.
      Inhibition kinetics of BChE were studied using butyrylthiocholine (BTCh) as
      substrate. The "1/v" versus "1/[BTCh]" plots in the absence (control plot) and in
      the presence of the metal ions intersected above 1/[BTCh]-axis for all trace
      elements. In addition, when the concentrations of the cations were increased at 4
      mM BTCh, velocities decreased and drove to zero at high concentrations of the
      trace elements. These results demonstrate that Ni2+, Co2+, and Mn2+ are linear
      mixed-type inhibitors of BChE. alphaK(i) values have been determined as 53.20
      mM,152.25 mM, and 190.24 mM for Ni2+, Mn2+, and Co2+, respectively, by using
      nonlinear regression analysis. From the comparison of alphaK(i) values of the
      trace elements, it can be said that BChE has more affinty to binding Ni2+ than
      Co2+ and Mn2+.

PMID- 14703993
TI  - Protein kinase CK1 from Trypanosoma cruzi.
AB  - A protein kinase activity, which uses casein as a substrate, has been purified to
      homogeneity from the epimastigote stage of Trypanosoma cruzi, by sequential
      chromatography on Q sepharose, heparin sepharose, phenyl sepharose, and alpha
      casein agarose. An apparent molecular weight of 36,000 was estimated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Gel filtration chromatography
      and sedimentation analyses demonstrated that the purified native enzyme is a
      monomer with a sedimentation coefficient of 2.9 S. The hydrodynamic parameters
      indicated that the shape of the protein is globular with a frictional ratio
      f/f(o) = 1.36 and a Stokes radius of 27.7 A. When two selective peptide
      substrates for protein kinases CK1 and CK2 were used (RRKDLHDDEEDEAM. SITA and
      RRRADDSDDDDD, respectively), the purified kinase was shown to predominantly
      phosphorylate the CK1-specific peptide. Additionally, the enzyme was inhibited by
      N-(2-amino-ethyl)-5-chloroisoquinoline-8-sulfonamide, a specific inactivator of
      CK1s from mammals. Based on these results, we concluded that the purified kinase
      corresponds to a parasite CK1.

PMID- 14703994
TI  - Immunohistochemical investigations of the autonomous innervation of the cervine
      testis.
AB  - The innervation of the cervine testis was studied in 6 roe deers, 7 red deers and
      14 fallow deers. The results for the three species are rather similar. With anti
      sera to neurofilament (NF) and neuron specific enolase (NSE), all small and large
      nerve fascicles can be demonstrated, but single fibers are incompletely stained.
      Immunoreactions against protein gene product-9.5 (PGP-9.5) and GAP-43 (growth
      associated protein-43) are better suited to depict the complete innervation
      pattern. Bundles of the superior spermatic and inferior spermatic nerves reach
      the testis via three access routes as funicular, mesorchial and caudal nerve
      contributions. We found no morphological evidence that the nerves in the cervine
      testis are directly involved in regulating Leydig cell function or seminiferous
      tubular motility. The majority of the testicular nerves are associated with the
      testicular arteries, but the musculature in the walls of the venous plexus
      pampiniformis is also innervated. All vascular nerve fibers represent
      postjunctional sympathetic axons displaying a strong dopamine-beta-hydroxylase
      (DBH) activity, mostly co-expressed with neuropeptide Y (NPY). The presence of
      cholinergic fibers in the testis of the deer is only sporadic and probably of no
      functional importance. In all three species of deer, a small quantity of
      myelinated nerve fibers is encountered in spermatic cord and tunica albuginea and
      regarded as afferent. The viscerosensory quality in the testicular intrinsic
      innervation is very likely mediated by the CGRP (calcitonin gene-related peptide)
      positive fibers that run independently from the testicular vessels and end in the
      connective tissue of spermatic cord and tunica albuginea. The testis of the red
      deer contains significantly more VIP (vasoactive intestinal polypeptide)-positive
      axons than that of roe and fallow deer. The nerve density in the interior of the
      testicular lobules shows no regional differences, but there are age- and season
      related changes that correlate with the developmental and functional state of the
      seminiferous tubules. Small testes with solid and narrow tubules, as seen in the
      prepuberal phase and during seasonal reproductive quiescence, are better
      innervated than large testes with expanded and spermatogenetically active
      seminiferous tubules.

PMID- 14703995
TI  - The spatial relationship between type I glomus cells and arteriolar myocytes in
      the mouse carotid body.
AB  - The structural relationship between type I glomus cells and the vascular smooth
      muscle was investigated by electron microscopy in the mouse carotid body. A close
      apposition (<0.1 microm) between the glomus parenchyma and the neighbouring
      arterioles was regularly present. Profiles of type I glomus cells were found to
      be exposed to the vascular smooth muscle without any supporting cell investment.
      In circumscribed areas of these profiles, type I glomus cells and the vascular
      smooth muscle cells made contact by fusion of their basal laminae. These glomus
      cell-myocyte junctions structurally resemble vascular neuromuscular junctions of
      sympathetic nerve terminals. In addition to the occurrence of such glomus cell
      myocyte contacts, myoendothelial junctions also appeared frequently. On the basis
      of these observations, it is suggested that type I glomus cells play a role in
      the regulation of the vascular tone in the carotid body and that a physiological
      interaction between the endothelial cells, the vascular smooth muscle cells and
      the type I glomus cells exists.

PMID- 14703996
TI  - Distributional changes of BrdU, PCNA, E2F1 and PAL31 molecules in developing
      murine palatal rugae.
AB  - The distribution of cells incorporating bromodeoxyuridine (BrdU) and the
      expression of molecules involved in the control of cell proliferation
      (proliferating cell nuclear antigen [PCNA], a cellular factor in F9
      teratocarcinoma cells that recognizes an adenovirus E1A inducible promoter 1
      [E2F1] and proliferation-related acidic nuclear protein 31 [PAL31]) during
      morphogenesis of the murine palatine rugae (PR) was examined histochemically.
      Pattern formation of the PR rudiment was initiated with cell cycle related
      molecules in the epithelium of the primary palate. Cells which had incorporated
      BrdU were detected at the outer areas of the presumptive epithelial placode (EP)
      and the EP at 11.5-13.5 days post coitum (dpc) and the outer areas of the PR
      protrusion after 14.5 dpc. The number of PCNA-positive cells at the central area
      of the PR protrusion decreased after 16.5 dpc. E2F-positive cells were detected
      at the outer areas of the PR protrusion at 15.5 and 16.5 dpc. The number of PAL31
      positive cells at the presumptive EP area and the already-formed EP area was
      decreased at 11.5-13.5 dpc. In two dimensional histological reconstructions,
      PAL31 expression approximately corresponded to the distribution of BrdU-positive
      cells at 11.5 and 13.5 dpc. EP placode formation might be regulated by
      spatiotemporal cell proliferation control involving the expression of the PAL31
      molecule. Following EP formation, PR development and growth control involved the
      expression of E2F1 and PCNA molecules.

PMID- 14703997
TI  - Cardiac developmental onomatology: the real heart of the matter.
AB  - There has been much controversy regarding Cardiac Embryology since the 19th
      Century; this has brought up contradictions over many studies on Cardiac
      Development, and stems mainly from semantic differences rather than from
      scientific observations. In 1998, FCAT published the 1st Edition of Terminologia
      Anatomica, which did not include Terminologia Embryologica, and to this day, we
      do not have a thorough compilation of Terminology related to Cardiac Development
      (O'Rahilly and Muller 1996). In the present study we have reviewed the literature
      from the 19th and 20th Centuries gathering the terms proposed by those scientists
      who influenced Prenatal Cardiac Terminology. Our aim is to bring to the attention
      of clinicians and researchers of cardiac morphogenesis the need to undertake a
      reform of the Developmental Cardiac Terminology. We believe an International
      Consensus on the terminology to be used during the developmental stages is
      urgent; it should be meaningful both to the experimental embryologist and to the
      cardiologist, without being ambiguous or controversial. We must not forget that a
      terminology is of value only when it is properly used.

PMID- 14703998
TI  - An anatomical study of the human cardiac veins with special reference to the
      drainage of the great cardiac vein.
AB  - Many case reports in which the main aim was to clarify the development of the
      superior vena cava (SVC) with persistent SVC have so far been published. However,
      there have only been a few systematic studies of the cardiac veins. Therefore, we
      macroscopically investigated the cardiac veins using 337 human adult hearts to
      obtain a detailed understanding of the morphology of the heart. From our study,
      we obtained the following results. 1. The frequency of persistent left SVC
      including one case of bilateral SVC was observed to be higher 7 cases (2.1%) than
      in previous reports. 2. We observed a second case in which the great cardiac vein
      drained directly into the right SVC (the first case being reported by Bergman et
      al. 1988). 3. Variations in the drainage of the great cardiac vein (GV) were
      observed from the right SVC to the left SVC, while the middle cardiac vein (MV)
      showed less variations of the drainage and course. 4. The drainage boundary
      between the GV and MV was classified into 3 types: MV-dominant type in 123 cases
      (36.5%), intermediate type in 182 cases (54.0%), and GV-dominant type in 32 cases
      (9.5%). From our results, we speculated that the MV did not generate any
      variations due to its short course before draining into the right atrium, while
      the GV had many variations due to its long course before draining into the right
      atrium. From the few GV-dominant types, the halfway boundary between the anterior
      (GV) and posterior (MV) route for drainage into the right atrium could be
      considered to be the anterior side rather than the Apex cordis.

PMID- 14703999
TI  - Morphological characteristics of dopaminergic immunoreactive neurons in the
      olfactory bulb of the common marmoset monkey (Callithrix jacchus).
AB  - The present study describes the distribution of tyrosine hydroxylase (TH)
      immunoreactive (IR) elements in the olfactory bulb of the common marmoset monkey
      (Callithrix jacchus), a primate species by immunohistochemistry. We identified
      six layers of the olfactory bulb of the common marmoset monkey in sections
      stained with cresyl violet. The majority of TH-IR cells were found in the
      glomerular layer. A few TH-IR cells were present in the external plexiform and
      granule cell layers. TH-IR fibers were identified in all layers of the olfactory
      bulb. The density of these nerve fibers was high in the internal plexiform and
      granule cell layers. The results in the olfactory bulb of the common marmoset
      monkey are generally similar to previous reports in some mammals. These data
      suggest that TH in the olfactory bulb of the common marmoset monkey may play a
      role in olfactory transmission via the glomeruli like in other mammals.

PMID- 14704000
TI  - Correlated expression of inducible nitric oxide synthase and P53, Bax in benign
      and malignant diseased gallbladder.
AB  - Our goal has been to investigate the expression and correlated significance of
      inducible nitric oxide synthase (iNOS) and P53, Bax in benign and malignant
      gallbladder diseases. We detected the expression of iNOS, P53 and Bax in the
      gallbladder wall by SP immunohistochemistry in 16 cases of chronic cholecystitis,
      11 cases of chronic cholecystitis with adenomyoma and 24 cases of gallbladder
      adenocarcinoma. The percentage of positively marked tumor cells was counted under
      microscope and the intensity of immunoreactivity was graded. SPSS10.0 statistical
      software was applied for statistical analysis. In this study, we found that: (1)
      Both benign and malignant diseased gallbladder wall expressed iNOS and Bax.
      Compared to benign diseased gallbladders, their expression in adenocarcinoma was
      decreased (p < 0.05), P53 was expressed strongly only in nuclei of adenocarcinoma
      cells of some cases. (2) In benign and malignant diseased gallbladders, iNOS
      expression was related positively to Bax (p < 0.01), the expression of P53 and
      Bax had a negative relationship (p < 0.01). The results suggested that both
      chronic cholecystitis and chronic cholecystitis with adenomyoma carry the risk of
      becoming malignant, especially the latter. NO is an important mediated molecule
      in cancer, there are intimate relationships between gallbladder cancer and
      apoptosis.

PMID- 14704001
TI  - Ultracytochemical demonstration of glycoproteins in the canine knee synovium.
AB  - By various ultracytochemical methods, glycoconjugates of the synoviocytes, the
      intercellular matrix and the wall of the small capillaries were studied in the
      synovial intimal tissues of the canine knee joint. Glycoconjugates with vicinal
      diol groups could be visualized in certain elements of the Golgi complex,
      lysosomes, vacuoles, the majority of intracellular cytomembranes, the surface
      coat of the plasma membrane and glycogen particles in type A cells. In type B
      cells, less-developed Golgi complexes, and fewer lysosomes and vacuoles were
      present in the cytoplasm than in that of type A cells. In contrast, a large
      number of cytoplasmic glycogen particles and abundant vicinal diol-containing
      groups in the surface coat of the plasma membrane became especially obvious in
      the B cells. Abundant neutral and acidic glycoproteins were observed in fibrous
      components in the intercellular matrix. In the small capillaries, strongly
      positive staining intensities for neutral and acidic glycoconjugates were
      observed in the basement membrane and perivascular connective tissue, as well as
      in the surface coat of the luminal plasma membrane of the endothelial cells,
      although to a somewhat weaker degree. Sialic acid, particularly, was notable in
      the surface coat of the latter cells. In addition, glycoproteins in the type A
      cells were shown by lectin ultracytochemistry to contain a variety of saccharide
      residues such as alpha-D-mannose, alpha-D-glucose, alpha-L-fucose, N-acetyl-beta
      D-glucosamine, and N-acetyl-neuraminic acid, which were also found in the plasma
      membrane of the B cells. The properties of the glycoconjugates found are
      discussed in relation to the basic functions assigned to the synovial membrane of
      the canine knee joint.

PMID- 14704002
TI  - Nuclear medical PET-study in the causal relationship between mastication and
      brain function in human evolutionary and developmental processes.
AB  - The principal author (Kubote 1995, 1997, 1998, 1999, 2000 a, b) has proposed that
      chewing food well from infancy will lead to a clear-headed and robust person,
      following which the same concept has been presented to the general public by the
      mass media. Unfortunately, however, there does not yet seem to be any direct
      evidence to support this claim. It is thus necessary to review mastication from
      the standpoint of the new concept of evidence-based medicine (EBM) and to create
      a new direction in medicodental research and treatment from the viewpoint of
      human evolution, because the causal relationship between mastication and brain
      function has never been clarified either in fossil science research or in the
      modem scientific bibliography. To confirm the human historical fossil record in
      regard to the causal relationship between the development of mastication and
      brain function in human evolutionary processes, the effect of gum chewing on
      brain reaction was examined in humans by means of a positron-emission tomography
      (PET) camera (Momose et al. 1997) after an antecubital intravenous injection of
      H215O. Powerful activation of the cortical cells was demonstrated in multiple
      cortical areas involving the marginal areas of the bilateral central sulci of the
      cerebral cortex (Fig. 1), and the activated areas coincided with our previous
      results in region of interest (ROI) analysis (Momose et al. 1887). Three
      dimensionally, numerous cortical cells were shown to form nuclei on relief maps
      (Fig. 2). As diets and feeding habits changed in a stepwise manner from
      frugivorous to omnivorous via herbivorous and carnivorous over the lengthy
      progress of evolution, the brain concomitantly grew and the cranial capacity
      gradually increased in volume from 500 cm3, food from plant sources to animal
      sources (700 cm3), and then to both (1500 cm3), during the human evolutionary and
      developmental processes. Gradual increases in the cranial capacity of human
      fossils during the developmental stage have been demonstrated also by PET images
      of the human brain acquired by means of a PET camera and an antecubital
      intravenous injection of H215O during mastication that showed powerful activation
      of cortical cells in multiple areas. It could be concluded that human fossils
      give us concrete information on how to feed our children in the modern human life
      style from infancy to adulthood, so that we should bring children up by adhering
      to images of the principal feeding habits discovered during this research on
      human evolutionary and developmental processes.

PMID- 14704003
TI  - Accessory obturator nerves with bilateral pseudoganglia in man.
AB  - During the routine dissection of the pelvis and anterior thigh of an adult female
      cadaver, accessory obturator nerves were found bilaterally with pseudoganglia. In
      addition, each accessory obturator nerve rejoined the anterior division of the
      normally placed obturator nerves after traveling superficial to the pubic bones.
      Histological sections revealed primarily normal nerve with no neuronal cell
      bodies within these focal areas of enlargement. No inflammatory response was
      noted in these histologically normal peripheral nerve structures. Further gross
      anatomy including other peripheral nerves was found to be normal. Peripheral
      nerve "ganglia" are found in the literature with little focus on histology. Our
      case report represents to our knowledge, the first report of a pseudoganglion in
      association with an accessory obturator nerve.

PMID- 14704004
TI  - Osteometric study of metapodial bones in sheep (Ovis aries, L. 1758).
AB  - This study, based on a sample of 215 individuals, gives detailed insight into
      Sheep metapodial bone main features: their variability and correlations between
      their various parts. This data allowed us to reveal the most relevant
      measurements for study of metapodial bones in sheep (GL, Bp, Dp, SD, DD, Bd, and
      Dd), as well as references used to split up the main population. Those references
      give a great help in placing any sample in relation to the breeds described in
      this work. The main purpose of this tool is to compare unknown populations, such
      as fossil ones, to present sheep breeds, in order to increase our knowledge of
      domesticated Sheep History, from its origins to the present day.

PMID- 14704005
TI  - Anatomical study of human adductor hallucis muscle with respect to its origin and
      insertion.
AB  - The adductor hallucis muscle (ADH) is evolutionally and functionally important,
      but no detailed morphological data about this muscle in the human body is
      available. In the present study, we examined the origin and insertion of the
      oblique and transverse heads of the ADH. Forty-five feet (20 right, 25 left) of
      34 cadavers (13 men, 21 women, average age of 80 years old) were used in the
      present study. The origin, insertion and nerve supplies of the oblique and
      transverse heads of the ADH were macroscopically examined in detail. Most
      commonly, the oblique head of the ADH arose from the bases of the 2nd, 3rd and
      4th metatarsal bones, the plantar metatarsal ligaments spanned between the bases
      of the 2nd, 3rd and 4th metatarsal bones, the lateral cuneiform bone, the fibrous
      sheath of the tendon of the peroneus longus muscle and the long plantar ligament,
      and inserted into the lateral sesamoid bone of the great toe and the capsule of
      the 1st metatarsophalangeal joint. Most commonly, the transverse head of the ADH
      originated from the capsules of the 3rd and 4th (and occasionally 5th)
      metatarsophalangeal joint and the deep transverse metatarsal ligaments, and
      inserted into the lateral sesamoid bone of the great toe, the capsule of the 1st
      metatarsophalangeal joint and lateral surface of the base of the 1st proximal
      phalanx. This muscle was classified into four types based on the origin of its
      oblique head and was classified into three types based on the origin of its
      transverse head. The percent ratio of the weight of the oblique head to the total
      weight of all the intrinsic muscles of the foot was 9.4% +/- 1.5, and the
      transverse head was 1.5% +/- 0.6 (n = 14). The transverse head of ADH tends to be
      reduced in size in the human, but the oblique head is well developed with no sign
      of reduction.

PMID- 14704006
TI  - The role of Austrian physicians and Prof. Joseph Hyrtl (1810-1894) on
      modernization of Ottoman-Turkish medicine.
AB  - Medical schools have a long history in Ottoman-Turkish medical education. At
      Ottoman medical schools (medreses), education has been given to students
      regularly. But because of social dogma and oppression of religion on the science
      of human anatomy they could not get a chance to improve for centuries.
      Traditionally, Ottoman-Turkish medical education was shaped under the influence
      of Galenos (129-200) and Avicenna (980-1037). These influences continued until
      the beginning of the 19th century. In this period, Avicenna's most famous medical
      book "Kanun-i fit-tip" was a main anatomy textbook in medical education of the
      eleventh century. Modernization of educational systems in the Ottoman Empire
      started during the reign of Sultan Selim the 3rd (1789-1807) and modern anatomy
      in Ottoman-Turkish Medicine has flourished following the Austrian physicians.
      Today's Department of Anatomy at Istanbul Medical School of the Istanbul
      University is a continuation of Galatasaray Medical School which was the first
      medical school achieving the western educational level.

PMID- 14704007
TI  - A sin of omission.

PMID- 14704008
TI  - Enhanced biological phosphorus removal from wastewater by biomass with different
      phosphorus contents, Part I: Experimental results and comparison with metabolic
      models.
AB  - Enhanced biological phosphorus removal (EBPR) in waste-water treatment involves
      at least two types of bacterial metabolism: a polyphosphate-accumulating
      metabolism (PAM) and a glycogen-accumulating metabolism (GAM). Laboratory-scale
      sequencing batch reactors operated in an anaerobic-aerobic cycle confirmed that
      low influent phosphorus/chemical oxygen demand (COD) ratio feed favored a GAM
      dominated culture and high influent phosphorus/COD ratio feed favored a PAM
      dominated culture, as indicated by changes in phosphorus, acetate, glycogen, and
      polyhydroxyalkanoate (PHA) concentrations during the anaerobic phase.
      Differential PAM and GAM dominance may explain variance in anaerobic phosphorus
      release, glycogen degradation, and PHA synthesis per acetate uptake ratios
      previously reported in EBPR systems and proposed metabolic models. The
      measurement of the ratios of anaerobic phosphorus release to acetate uptake and
      glycogen degradation to acetate uptake is suggested as an assay to estimate the
      relative dominance of PAM and GAM, respectively, in EBPR cultures.

PMID- 14704009
TI  - Enhanced biological phosphorus removal from wastewater by biomass with different
      phosphorus contents, Part II: Anaerobic adenosine triphosphate utilization and
      acetate uptake rates.
AB  - Data from laboratory-scale sequencing batch reactors operated in an anaerobic
      aerobic cycle showed that a low influent phosphorus/chemical oxygen demand (COD)
      ratio feed favored a glycogen-accumulating metabolism (GAM)-dominated culture and
      that a high influent phosphorus/COD ratio feed favored a polyphosphate
      accumulating metabolism (PAM)-dominated culture. The PAM-dominated culture
      anaerobically took up acetate approximately 7 times faster than the GAM-dominated
      culture. Adenosine triphosphate (ATP) balances were performed assuming eight
      different metabolic scenarios that included the Entner-Doudoroff or the Embden
      Myerhof glycolytic pathway, acetyl-coenzyme A (CoA) synthase or the acetate
      kinase-phospho-transacetylase (AK-PTA) system for acetyl-CoA synthesis, and ATP
      synthesis or no ATP synthesis during fumarate reduction. The ATP available for
      transport of acetate into the cell (2) was calculated using these balances. The
      assumed quantity of ATP produced during fumarate reduction had a relatively small
      effect on alpha, particularly when PAM was dominant. When GAM was dominant,
      little or no ATP was available for acetate transport depending on the assumed
      scenario, and the Embden-Myerhof pathway was more feasible. The value of alpha
      increased with increasing PAM dominance for all eight metabolic pathways. The
      maximum calculated alpha value of 0.5 mol ATP/C-mol acetate uptake occurred at
      maximum PAM dominance and when the Embden-Myerhof pathway was active, when ATP
      was produced during fumarate reduction, and when the AK-PTA system was active.
      This value of alpha was higher than previously calculated values with the same
      metabolic assumptions. An acetate uptake mechanism was suggested that included
      acetyl-CoA synthetase and direct regeneration of the proton motive force by a
      proton-translocating pyrophosphatase. Polyphosphate-accumulating metabolism may
      have a competitive advantage over GAM through a higher anaerobic acetate uptake
      rate made possible by a greater use of energy for acetate uptake, by use of a
      different acetate uptake mechanism, or both.

PMID- 14704010
TI  - Enhanced biological phosphorus removal from wastewater by biomass with different
      phosphorus contents, Part III: Anaerobic sources of reducing equivalents.
AB  - Laboratory-scale sequencing batch reactors exhibiting enhanced biological
      phosphorus removal (EBPR) operated at different influent phosphorus/chemical
      oxygen demand (COD) ratios were analyzed to evaluate possible anaerobic sources
      of reducing equivalents. Assuming anaerobic glycogen degradation was the sole
      anaerobic reducing equivalent source, an anaerobic phase carbon balance showed
      that glycogen-accumulating metabolism (GAM)-dominated systems were nearly carbon
      balanced, but that polyphosphate-accumulating metabolism (PAM)-dominated systems
      had end-anaerobic phase carbon deficits. An anaerobic-phase reducing equivalent
      balance showed a reducing equivalent excess for the GAM-dominated systems and a
      deficit for the PAM-dominated systems, suggesting that glycogen degradation was
      not the sole reducing equivalent source for PAM. Reducing equivalent balances
      showed that metabolic models including complete anaerobic tricarboxylic acid
      (TCA) cycle activity, partial TCA cycle activity, and the glyoxylate bypass could
      provide the reducing equivalents required in PAM. Metabolic precursors produced
      in glycolysis, the TCA cycle, or modified versions of the TCA cycle could allow
      anaerobic growth and account for the PAM carbon deficits. The importance of
      considering both PAM and GAM activity in evaluating EBPR metabolic models was
      illustrated.

PMID- 14704012
TI  - Performance evaluation of a cloth-media disk filter for wastewater reclamation.
AB  - A cloth-media disk filter (CMDF) was evaluated as an alternative to granular
      medium filtration for use in wastewater recycling applications. The CMDF was
      effective for filtration of effluent from an activated-sludge treatment process.
      Effluent turbidity values from the CMDF were consistently less than California's
      wastewater recycling application limit of 2 nephelometric turbidity units (NTU)
      for influent turbidity values of up to 25 NTU at hydraulic loading rates varying
      between 7 and 15 m/h (2.86 and 6.1 gpm/sq ft). The filter produced 154 m/d (3781
      gpd/sq ft) at a hydraulic loading rate of 7 m/h (2.86 gpm/sq ft) with high
      turbidity (6 to 25 NTU) and 330 m/d (8102 gpd/sq ft) at a hydraulic loading rate
      of 15 m/h (6.1 gpm/sq ft) with low influent turbidity (< or = 6 NTU/m2 [6 NTU/sq
      ft] of filter cloth). The backwash water required by the CMDF at HLRs between 7
      and 15 m/h (2.86 and 6.1 gpm/sq ft) and corresponding solids loading rates
      between 5 and 32 kg/(m2 x d) (0.21 and 1.35 lb/d/sq ft) varied from 2 to 10% of
      the total influent flow. Thus, the CMDF could consistently meet the recycling
      requirements of a turbidity less than 2 NTU over a broad range of influent
      turbidity values and hydraulic loading rates.

PMID- 14704011
TI  - Evaluation of odor characteristics of heat-dried biosolids product.
AB  - Because it produces an exceptional quality pellet product, heat drying of
      wastewater solids from municipal wastewater treatment plants is becoming more
      prevalent as biosolids management regulations become more restrictive. The
      product from heat drying is sometimes odorous as dry or wetted pellets. The
      odors, although not regulated, can be important for marketability and public
      acceptance of the product. The reasons for the odors are usually a result of
      upstream processing and management of wastewater solids prior to drying. The
      goals of this study were to determine odor characteristics and to compare the
      odors produced by evaluating odors from four types of heat-dried biosolids
      products: all undigested; primary digested-waste activated sludge (WAS)
      undigested; all digested; and WAS lime stabilized pellets. The results are
      described in this paper.

PMID- 14704013
TI  - Effect of solids retention time on the performance of thermophilic and mesophilic
      digestion of combined municipal wastewater sludges.
AB  - The steady-state performance of thermophilic (55 degrees C) and mesophilic (35
      degrees C) anaerobic digestion as a function of solids retention time (SRT) was
      evaluated in laboratory digesters at SRTs ranging from 4 to 15 days, and in pilot
      plant digesters at a 20-day SRT. All of the digesters were fed the same source of
      municipal combined primary and secondary waste sludge. The destruction efficiency
      of volatile solids increased from 53% to 66% as the SRT was increased from 6 days
      to 20 days. The average destruction efficiency of volatile solids was 3
      percentage points higher for the thermophilic digester at the 6-day SRT and
      approximately 1 percentage point higher for the higher SRTs, but the difference
      was only statistically significant at the 15-day SRT. Based on volatile suspended
      solids measurements, the thermophilic solids destruction efficiency was
      approximately 4 percentage points higher at the 10- and 15-day SRTs. At a 4-day
      SRT, methanogenic activity could only be maintained in the thermophilic digester.
      The pH, alkalinity, ammonia, volatile fatty acid, and soluble chemical oxygen
      demand concentrations were higher for the thermophilic digester at each SRT. At
      SRTs of 10 days and less, the thermophilic digester had a much higher propionate
      and slightly higher butyrate concentration. Carbohydrates were readily degraded
      by both digesters, protein was the major component in the sludge at the long
      SRTs, and lipid degradation increased with increasing SRT.

PMID- 14704014
TI  - Evaluation of different methods for the determination of maximum heterotrophic
      growth rates.
AB  - This work evaluated the most commonly used methods for determining maximum
      heterotrophic specific growth rates (mum) in batch reactors. Parallel batch
      experiments were conducted under various initial substrate-to-biomass (S0/X0)
      ratios and values of the solids retention time (thetac). The maximum specific
      growth rate, mum, was determined simultaneously according to measurements of
      oxygen consumption (i.e., oxygen uptake rate, OUR) and volatile suspended solids
      (VSS) increase. The S0X0 ratio was found to significantly influence mum values.
      Under high S0/X0 ratios (= 20), fast-growing bacteria seemed to gain a
      competitive advantage resulting in higher mum values than those obtained under
      low S0/X0 ratios (= 1.5). The OUR-based estimate of mum (mum(OUR)), under certain
      circumstances, is differentiated from mum that is based on exponential bacterial
      growth (mum(VSS)), and seems to be more a measure of substrate oxidation than a
      measure of bacterial growth. At high S0/X0 ratio and low thetac, mum(OUR) was
      significantly higher than the mum(VSS), indicating that considerable uncoupling
      between anabolism and catabolism was occurring under these conditions. Batch
      experiments conducted at high S0/X0 ratios seemed to be a more sensitive method
      for determining mum values in the presence of an inhibitor than tests conducted
      at low S0/X0 ratios.

PMID- 14704015
TI  - Perceptual implicit memory relies on intentional, load-sensitive processing at
      encoding.
AB  - In two experiments, we examined whether the encoding processes leading to
      perceptual implicit memory satisfied the intentionality and load insensitivity
      criteria for automaticity. Whether participants intended to process words or
      digits, in displays containing both, was manipulated in Experiment 1. Results
      showed an effect of intention on a subsequent perceptual identification task and
      a recognition task. Load (one, two, and four words) and exposure duration (1,000,
      600, and 200 msec) at encoding were manipulated in Experiment 2. Recognition was
      affected by both variables, but performance on the perceptual identification task
      was affected only by load. In both experiments, the results showed that
      controlled (intentional, load-sensitive) processing of words at encoding is
      essential for later perceptual implicit memory. That is, the encoding processes
      leading to perceptual implicit memory fail both criteria of automaticity.

PMID- 14704016
TI  - Repetition priming mediated by task similarity in semantic classification.
AB  - In the present study, the specificity of repetition priming between semantic
      classification tasks was examined using Osgood's (Osgood, Suci, & Tannenbaum,
      1957) semantic space as a heuristic for determining the similarity between
      classifications. The classification tasks involved judging the meaning of words
      on semantic scales, such as pleasant/unpleasant. The amount of priming across
      classifications was hypothesized to decrease with increasing distance (decreasing
      similarity) between semantic scales in connotative semantic space. The results
      showed maximum repetition priming when the study and the test classifications
      were the same, intermediate degrees of priming when the study and the test
      classification scales shared loadings on semantic factors, and little priming
      when the study and the test classification scales loaded primarily on orthogonal
      semantic factors--that is, when the distance between scales was maximized.
      Consistent with the transfer-appropriate processing framework, repetition priming
      in semantic classifications was highly task specific, decreasing with increasing
      distance between classification scales.

PMID- 14704017
TI  - The effects of divided attention at encoding on item and associative memory.
AB  - Divided attention at encoding is well known to have adverse effects on episodic
      memory performance (e.g., Naveh-Benjamin & Greg, 2000). This article attempts to
      determine whether these effects are a result of the interruption of encoding of
      associative information among the components of an episode. Five experiments,
      using different types of episodes and episodes components, were conducted.
      Participants studied information under either full or divided attention and were
      then tested on their memory for both the episodes' components and the
      associations between them. Divided attention did not produce a differential
      deficit in memory for associative information; memory for the components suffered
      to the same degree as memory for the associations among the components. The cause
      of the divided-attention effect at encoding lies somewhere other than in the
      associative processes that are engaged.

PMID- 14704018
TI  - The effects of associations and aging on illusory recollection.
AB  - Younger and older adults (mean years = 20.5 and 75) studied lists of associated
      words for a final recognition test. The length (5, 10, or 15 associates) and
      modality (auditory or visual) of study lists were manipulated within subjects.
      For both groups, increasing the number of associates increased illusory
      recollections of a related lure's presentation (measured by source judgments and
      the Memory Characteristics Questionnaire). This pattern suggests that associative
      activation of the lure influenced illusory recollection, and aging spared this
      process. In contrast, age impaired the recollection of source for studied words
      (auditory or visual) and had identical effects on source attributions for related
      lures. This pattern suggests that the true recollection of source influenced
      illusory recollection of source, and age impaired this process. To account for
      these and other results, we propose that associative activation drives an
      attribution process that binds subjectively detailed features to a false memory.

PMID- 14704019
TI  - Novelty effects on recollection and familiarity in recognition memory.
AB  - Recognition memory is better for novel or distinctive items than for non-novel
      items. However, it is not known whether these effects reflect changes in
      recollection or in familiarity-based recognition judgments. Some previous results
      have indicated that recollection should be more sensitive to novelty than to
      familiarity, whereas other results have suggested the opposite. We used avon
      Restorff paradigm in which a small proportion of studied items were made novel by
      presenting them in a color different from that of the majority of the study
      items. Memory was tested using a remember-know procedure. Across two experiments,
      stimulus novelty was found to benefit both recollection and familiarity. The
      effects on familiarity were observed under intentional and incidental encoding
      conditions, whereas the effects on recollection were significantly reduced, and
      no longer significant, under incidental as compared with intentional encoding
      conditions. Thus, both processes benefit from stimulus novelty, but the extent to
      which recollection benefits from novelty depends on the encoding condition.

PMID- 14704020
TI  - Transferring voice effects in recognition memory from remembering to knowing.
AB  - In five experiments, we investigated the effects of voice congruency (same vs.
      different voices at study and at test) on remembering and knowing in recognition
      memory. With low- and medium-frequency three- or four-syllable words, a voice
      congruency effect occurred only in remembering. With nonwords, voice congruency
      effects occurred both in remembering and in knowing. With nonwords and divided
      attention at study, the voice congruency effect transferred almost completely
      from remembering to knowing. By showing a transfer of effects from remembering to
      knowing as encoding became more impoverished, these findings support a
      distinctiveness/fluency account of remembering and knowing as well as the theory
      that remembering and knowing indicate retrieval of events from episodic and
      semantic memory systems, respectively.

PMID- 14704021
TI  - Subjective measures of awareness and implicit cognition.
AB  - In this article, we examine whether artificial grammar learning is implicit
      according to a subjective criterion of awareness based on confidence ratings. In
      four experiments, participants discriminated between grammatical and
      ungrammatical sequences in both the same (Experiment 1) and a novel (Experiments
      2-4) vocabulary and indicated their confidence in each decision. Replicating
      earlier studies, confidence judgments reported on a continuous scale (50%-100%)
      were only weakly related to accuracy, suggesting that learning was implicit. In
      contrast, confidence judgments reported on a binary scale (high vs. low) revealed
      that confidence was related to accuracy. We show that participants are better
      able to place their phenomenal states on a binary scale, as compared with a
      continuous scale.

PMID- 14704022
TI  - Imagery perspective and source monitoring in imagination inflation.
AB  - The present experiments suggest that imagery perspective--first person (own)
      versus third person (observer's)--influences source-monitoring judgments.
      Imagination inflation (Garry, Manning, Loftus, & Sherman, 1996) occurs when
      imaginary experience with events is mistaken for real experience. In Experiment
      1, the perspective used to visualize real past events depended on memory test
      wording ("remember doing?" vs. "happened to you?"). Experiment 2 manipulated the
      perspective used to visually imagine counterfactual events and showed that the
      effect on imagination inflation depended on memory test wording. Imagination
      inflation was most likely when memory test wording encouraged participants to
      visualize real events from the same perspective as they had used to imagine
      counterfactual ones. Imagination inflation may result not simply from having
      created imaginary representations of events, but also from having created
      representations that match the decision criteria used in source monitoring.

PMID- 14704023
TI  - Redescription disembeds relations: evidence from relational transfer and use in
      problem solving.
AB  - How relational information becomes disembedded from its original context is an
      important issue for theories of cognition. Two experiments tested the hypothesis
      that a process called redescription disembeds relations, resulting in abstract
      and, therefore, more transferable and robust representations. In Experiment 1,
      participants solved simple problems involving an alternating sequence.
      Participants who discovered the alternating-sequence relation through
      redescription transferred the relation to a second type of problem more quickly
      and used it more consistently than did participants who had been directly
      instructed on the alternating-sequence strategy. Experiment 2 showed similar
      effects for participants who discovered the alternating-sequence relation through
      redescription, as compared with participants who had discovered the relation
      through information available in the display. The present results converge with
      previous experimental and correlational evidence that suggests that redescription
      creates abstract representations of relations.

PMID- 14704024
TI  - The roles of the convex hull and the number of potential intersections in
      performance on visually presented traveling salesperson problems.
AB  - The planar Euclidean version of the traveling salesperson problem requires
      finding the shortest tour through a two-dimensional array of points. MacGregor
      and Ormerod (1996) have suggested that people solve such problems by using a
      global-to-local perceptual organizing process based on the convex hull of the
      array. We review evidence for and against this idea, before considering an
      alternative, local-to-global perceptual process, based on the rapid automatic
      identification of nearest neighbors. We compare these approaches in an experiment
      in which the effects of number of convex hull points and number of potential
      intersections on solution performance are measured. Performance worsened with
      more points on the convex hull and with fewer potential intersections. A measure
      of response uncertainty was unaffected by the number of convex hull points but
      increased with fewer potential intersections. We discuss a possible
      interpretation of these results in terms of a hierarchical solution process based
      on linking nearest neighbor clusters.

PMID- 14704025
TI  - Counterexamples in sentential reasoning.
AB  - How do logically naive individuals determine that an inference is invalid? In
      logic, there are two ways to proceed: (1) make an exhaustive search but fail to
      find a proof of the conclusion and (2) use the interpretation of the relevant
      sentences to construct a counterexample--that is, a possibility consistent with
      the premises but inconsistent with the conclusion. We report three experiments in
      which the strategies that individuals use to refute invalid inferences based on
      sentential connectives were examined. In Experiment 1, the participants' task was
      to justify their evaluations, and it showed that they used counterexamples more
      often than any other strategy. Experiment 2 showed that they were more likely to
      use counterexamples to refute invalid conclusions consistent with the premises
      than to refute invalid conclusions inconsistent with the premises. In Experiment
      3, no reliable difference was detected in the results between participants who
      wrote justifications and participants who did not.

PMID- 14704027
TI  - Analysis and analogy in the perception of vowels.
AB  - In two experiments, we investigated the creation of conceptual analogies to a
      contrast between vowels. An ordering procedure was used to determine the
      reliability of simple sensory and abstract analogies to vowel contrasts composed
      by naive volunteers. The results indicate that test subjects compose stable and
      consistent analogies to a meaningless segmental linguistic contrast, some
      invoking simple and complex relational properties. Although in the literature of
      psychophysics such facility has been explained as an effect of sensory analysis,
      the present studies indicate the action of a far subtler and more versatile
      cognitive function akin to the creation of meaning in figurative language.

PMID- 14704026
TI  - Procedural learning in perceptual categorization.
AB  - In two experiments, observers learned two types of category structures: those in
      which perfect accuracy could be achieved via some explicit rule-based strategy
      and those in which perfect accuracy required integrating information from
      separate perceptual dimensions at some predecisional stage. At the end of
      training, some observers were required to switch their hands on the response
      keys, whereas the assignment of categories to response keys was switched for
      other observers. With the rule-based category structures, neither change in
      response instructions interfered with categorization accuracy. However, with the
      information-integration structures, switching response key assignments interfered
      with categorization performance, but switching hands did not. These results are
      consistent with the hypothesis that abstract category labels are learned in rule
      based categorization, whereas response positions are learned in information
      integration categorization. The association to response positions also supports
      the hypothesis of a procedural-learning-based component to information
      integration categorization.

PMID- 14704028
TI  - Does men's advantage in mental rotation persist when real three-dimensional
      objects are either felt or seen?
AB  - In several spatial tasks in which men outperform women in the processing of
      visual input, the sex difference has been eliminated in matching contexts limited
      to haptic input. The present experiment tested whether such contrasting results
      would be reproduced in a mental rotation task. A standard visual condition
      involved two-dimensional illustrations of three-dimensional stimuli; in a haptic
      condition, three-dimensional replicas of these stimuli were only felt; in an
      additional visual condition, these replicas were seen. The results indicated
      that, irrespective of condition, men's response times were shorter than women's,
      although accuracy did not significantly differ according to sex. For both men and
      women, response times were shorter and accuracy was higher in the standard
      condition than in the haptic one, the best performances being recorded when full
      replicas were shown. Self-reported solving strategies also varied as a function
      of sex and condition. The discussion emphasizes the robustness of men's faster
      speed in mental rotation. With respect to both speed and accuracy, the demanding
      sequential processing called for in the haptic setting, relative to the standard
      condition, is underscored, as is the benefit resulting from easier access to
      depth cues in the visual context with real three-dimensional objects.

PMID- 14704029
TI  - Transfer effects of incompatible location-relevant mappings on a subsequent
      visual or auditory simon task.
AB  - Two experiments investigated the influence of practice with an incompatible
      mapping of left and right stimuli to keypress responses on performance of a
      subsequent Simon task, for which stimulus location was irrelevant, after a delay
      of 5 min or 1 week. In Experiment 1, the visual Simon effect was eliminated when
      the practice modality was auditory and reversed to favor noncorresponding
      responses when it was visual, and there was no significant effect of delay
      interval. In Experiment 2, significant auditory Simon effects were obtained that
      did not vary as a function of practice modality, with delay having only a
      marginal effect on the magnitude of the Simon effect. The elimination of the
      visual Simon effect in the transfer session is most likely due to the short-term
      stimulus-response associations defined for the incompatible spatial mapping
      remaining active during the transfer session. Because the auditory Simon effect
      is stronger than the visual one, more practice with the incompatible mapping may
      be necessary to produce reliable transfer effects for it.

PMID- 14704030
TI  - International collaboration on childhood leukemia.
AB  - The current cure rate of childhood acute lymphoblastic leukemia has reached 80%
      in many industrialized countries, but in developing countries the rate is often
      less than 10%. To advance the cure rate, investigators have formed several
      parallel initiatives in both industrialized and developing countries through
      international collaboration and partnership. Among industrialized countries,
      investigators have combined data to conduct in-depth studies of the biology and
      heterogeneity of high-risk or drug-resistant subgroups of leukemia to identify
      optimal or novel treatments. Alliances have been established among government,
      local nongovernmental organizations, health care providers, and international
      groups to improve the survival rate of childhood leukemia in developing
      countries. "Twinning" partnerships between a well-established individual
      institution or study group and a pediatric cancer unit in a developing country
      has proved to be the most successful strategy to date.

PMID- 14704033
TI  - Gene expression profiling in childhood acute leukemia: progress and perspectives.
AB  - Recent advances in treatment have transformed childhood acute leukemias into
      curable diseases. However, 20% to 40% of acute leukemia patients still experience
      a relapse. Microarrays typically contain thousands of oligonucleotides or
      complementary DNAs and are rapidly becoming important research tools for the
      identification of novel classifications of leukemias and lymphomas. Microarray
      based identification of several translocations has been performed in acute
      lymphoblastic leukemia (ALL), leading to the discovery of t(1;19), t(12;21), and
      11q23 translocations, and in acute myeloid leukemia (AML), finding t(8;21),
      inv(16), and t(15;17). Correlations between gene expression profiles and clinical
      features have been reported in ALL and AML. Recently, it was reported that gene
      expression profiling can be used to predict the prognosis of childhood acute
      leukemia. In this report, the recent progress in microarray analysis of childhood
      acute leukemia is reviewed. Gene expression profiling provides new insights into
      the biological mechanisms of leukemogenesis and the prognosis of childhood acute
      leukemia.

PMID- 14704031
TI  - The role of the MLL gene in infant leukemia.
AB  - The MLL gene is a major player in leukemia, particularly in infant leukemia and
      in secondary, therapy-related acute leukemia. The normal MLL gene plays a key
      role in developmental regulation of gene expression (including HOX genes), and in
      leukemia this function is subverted by breakage, recombination, and chimeric
      fusion with one of 40 or more alternative partner genes. In infant leukemias, the
      chromosome translocations involving MLL arise during fetal hematopoiesis,
      possibly in a primitive lymphomyeloid stem cell. In general, these leukemias have
      a very poor prognosis. The malignancy of these leukemias is all the more dramatic
      considering their very short preclinical natural history or latency. These data
      raise fundamental issues of how such divergent MLL chimeric genes transform
      cells, why they so rapidly evolve to a malignant status, and what alternative or
      novel therapeutic strategies might be considered. We review here progress in
      tackling these questions.

PMID- 14704034
TI  - The signaling pathways of erythropoietin and interferon-gamma differ in
      preventing the apoptosis of mature erythroid progenitor cells.
AB  - Interferon (IFN)-gamma is a survival factor for mature erythroid progenitor
      cells. To elucidate related survival mechanisms, we compared the role of
      phosphatidylinositol 3-kinase (PI3-kinase) in the survival signals of IFN-gamma
      and erythropoietin (EPO). Human erythroid colony-forming cells (ECFCs) purified
      from peripheral blood were used, and Ly294002 was used as a PI3-kinase inhibitor.
      Treating ECFCs with a high concentration of Ly294002 (50 micromol/L) in the
      presence of EPO and/or IFN-gamma reduced cell viability by inducing apoptosis.
      However, treating cells with a lower concentration of Ly294002 (10 micromol/L)
      did not affect the antiapoptotic function of IFN-gamma and abolished the
      antiapoptotic effect of EPO. Adding IFN-gamma or EPO induced Bcl-x expression in
      ECFCs, as determined by Western blotting, and expression was suppressed in the
      presence of Ly294002. We also examined the phosphorylation of the protein kinase
      Akt, the downstream target of PI3-kinase. EPO stimulation significantly increased
      the level of Akt phosphorylation, but IFN-gamma did not. These results suggest
      that IFN-gamma plays a role in preventing the apoptosis of erythroid progenitor
      cells by affecting Bcl-x expression, thereby reducing the disruption of the
      mitochondrial transmembrane potential via PI3-kinase pathways that are related to
      but distinct from the EPO pathway.

PMID- 14704035
TI  - Iron deficiency anemia as the only sign of infection with Helicobacter pylori: a
      report of 9 pediatric cases.
AB  - Recently, an association between Helicobacter pylori (HP) and iron deficiency
      anemia (IDA) was proposed. We describe 9 pediatric patients with a history of
      long-standing IDA and HP infection. After HP test results were confirmed to be
      positive, anti-HP therapy consisting of omeprazole, clarithromycin, and
      amoxicillin was administered for 2 weeks. The hematologic profile and iron status
      were assessed before and periodically after the end of the eradication regimen.
      The eradication of HP was associated with stable normalization of iron stores. HP
      infection may be involved in cases of IDA of unknown origin, and the eradication
      of HP is associated with the resolution of anemia.

PMID- 14704032
TI  - Molecular pharmacodynamics in childhood leukemia.

PMID- 14704036
TI  - Molecular cytogenetic analyses of HIG, a novel human cell line carrying
      t(1;3)(p36.3;q25.3) established from a patient with chronic myelogenous leukemia
      in blastic crisis.
AB  - Chromosomal abnormalities involving 1p36, 3q21, and/or 3q26 have been reported in
      a subset of myeloid neoplasms having characteristic dysmegakaryopoiesis, and the
      overexpression of EVI1 on 3q26 or of MEL1 on 1p36 has been implicated in their
      pathogenesis. We describe molecular cytogenetic analyses of a novel human cell
      line, HIG, established from a unique case in which a novel translocation
      t(1;3)(p36;q26) appeared as the sole additional chromosomal abnormality at the
      time of blastic transformation of chronic myelogenous leukemia. The patient
      displayed clinical features resembling those of the 3q21q26 syndrome. The HIG
      cell line retained der(1)t(1;3)(p36;q26) but lost t(9;22)(q34;q11). To identify
      the relevant gene that would be deregulated by this translocation, we molecularly
      cloned the translocation's breakpoints. They were distant from the breakpoint
      cluster regions of the 3q21q26 syndrome or t(1;3)(p36;q21), and neither the EVI1
      nor the MEL1 transcript was detected in the HIG cell line. None of the genes
      located within 150 kilobase pairs of the breakpoints were aberrantly expressed,
      suggesting that in this case other gene(s) more distant from the breakpoints are
      deregulated by possible remote effects. Further analyses of the deregulated genes
      in the HIG cell line should provide important insight into the mechanisms
      involved in these types of leukemias.

PMID- 14704037
TI  - MLL/AF-1p fusion in therapy-related early pre-B acute lymphoblastic leukemia with
      t(1;11)(p32;q23) translocation developing in the relapse phase of acute
      promyelocytic leukemia.
AB  - We report the development of therapy-related early pre-B acute lymphoblastic
      leukemia in a patient administered a topoisomerase II inhibitor, etoposide, a
      consolidation therapy agent for acute promyelocytic leukemia. Our case is of
      interest because of simultaneous relapse of the original leukemia and onset of
      therapy-related leukemia and relatively rare t(1;11)(p32;q23) translocation with
      confirmed MLL/AF-1p fusion. This case suggests that careful monitoring for MLL
      gene rearrangements is necessary after administration of topoisomerase II
      inhibitors.

PMID- 14704038
TI  - The bisphosphonate zoledronic acid induces cytotoxicity in human myeloma cell
      lines with enhancing effects of dexamethasone and thalidomide.
AB  - Bisphosphonates have recently been introduced in the therapeutic armamentarium
      for long-term treatment of patients with multiple myeloma. These pyrophosphate
      analogs not only reduce the occurrence of skeletal events but also provide
      clinical benefit to patients and improve the survival of some of them. The
      existence of these capabilities raises the possibility that these compounds may
      have a direct antiproliferative effect on tumor cells. To investigate whether
      these drugs exert a direct antitumor effect, we exposed human myeloma cell lines
      ARH-77 and RPMI-8226 to increasing concentrations of zoledronic acid (ZOL) in
      vitro. A concentration- but not time-dependent cytotoxic effect was detected with
      drug treatment of ARH-77 and RPMI-8226 cell lines (30% and 60% at 48 hours and
      38% and 62% at 72 hours, respectively, for 50 microM of ZOL). Cytotoxicity was
      not due to ZOL-induced chelation of extracellular calcium as shown by control
      experiments with the calcium chelator ethylene glycol-bis(beta-aminoethylether)
      N,N,N',N'-tetraacetic acid. Addition of the competitive inhibitor of the nitric
      oxide synthase N omega-nitro-L-arginine methyl ester did not modulate ZOL-induced
      cytotoxicity. However, a decrease in the number of apoptotic cells was detected
      when protein kinase C was inhibited by addition of staurosporine to ZOL
      containing cultures. Cytotoxicity also was increased by addition of dexamethasone
      (Dex) and thalidomide (Thal) to ARH-77 and RPMI-8226 cultures. We demonstrated
      that exposing myeloma cell lines ARH-77 and RPMI-8226 to ZOL inhibits cell growth
      in a dose-dependent but not a time-dependent manner and that combination of Dex
      and Thal with ZOL induces apoptotic cell death, providing a rationale for
      potential applications in vivo.

PMID- 14704039
TI  - Hemophagocytic syndrome: an unusual manifestation of acute human immunodeficiency
      virus infection.
AB  - An 18 year-old heterosexual man was hospitalized because of fever, chills, a sore
      throat, and a dry cough for 8 days. He had had sexual intercourse with a new
      partner within the 4 months prior to admission. At admission, the patient
      presented a clinical picture compatible with hemophagocytic syndrome (HPS). The
      presence of hemophagocytosis was subsequently determined pathologically from bone
      marrow and lymph node specimens. An exhaustive diagnostic work-up failed to
      reveal any causative etiology, the symptoms improving after 2 doses of
      intravenous immunoglobulin (IVIG) infusion, given at a dose of 0.5 mg/kg each,
      the 2 doses being administered 1 week apart. Three months subsequent to the
      patient's initial presentation, acute human immunodeficiency virus (HIV)
      infection was diagnosed, and the patient received highly active antiretrovirus
      therapy (HAART) from the time of diagnosis. The patient remained well for the
      following 2 years. HPS in the advanced stages of HIV infection has previously
      been described, but HPS during seroconversion of an acute form of the infection
      is rare. We most definitely suggest, however, that acute HIV infection be
      included in the list of potential causes of HPS. IVIG therapy appears to be an
      appropriate therapeutic modality, and HAART also is effective, for prevention of
      recurrence of HPS in a patient with acute HIV infection.

PMID- 14704040
TI  - Autologous hematopoietic stem cell transplantation for 3 patients with severe
      juvenile rheumatoid arthritis.
AB  - We performed autologous CD34+ stem cell transplantation in 3 patients with
      juvenile rheumatoid arthritis (JRA) refractory to conventional treatment. All
      patients had systemic type JRA. In case 1 (a 3-year-old boy), purified CD34+
      cells from bone marrow were transplanted after a preconditioning regimen
      consisting of cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (40
      mg/kg). However, the disease flared soon after transplantation. In case 2 (a 13
      year-old girl) and case 3 (a 21-year-old woman), a preconditioning regimen
      consisting of etoposide (VP16) (2 g/m2), thiotepa (300 mg/m2), and ATG (40 mg/kg)
      was followed by transplantation of purified CD34+ stem cells harvested from
      peripheral blood mononuclear cells. The patients in cases 2 and 3 attained
      complete remission without any medication. Thus for patients with refractory JRA,
      autologous CD34+ cell transplantation appears to be a safe and feasible choice of
      treatment in terms of good quality of life. However, a greater number of patients
      and a longer observation period are needed before definitive conclusions can be
      drawn.

PMID- 14704041
TI  - Successful unrelated cord blood transplantation in an infant with Wiskott-Aldrich
      syndrome following recurrent cytomegalovirus disease.
AB  - We describe successful unrelated cord blood transplantation in a 14-month-old boy
      with Wiskott-Aldrich syndrome. He had been suffering from recurrent
      cytomegalovirus (CMV) pneumonia. Ganciclovir was given pretransplantation and
      posttransplantation, and CMV antigenemia was monitored as a marker of
      reactivation. The conditioning regimen was cyclophosphamide, busulfan, and
      antithymocyte globulin. The patient received an HLA 1-locus-mismatched cord blood
      unit, and the total number of infused nucleated cells was 9.0 x 10(7)/kg.
      Neutrophil engraftment was achieved on day +20, and a platelet count greater than
      50 x 10(9)/L was achieved on day +51. A normal lymphoproliferative response to
      phytohemagglutinin mitogen was detectable 7 months posttransplantation. Long-term
      use of ganciclovir prevented CMV reactivation and did not compromise engraftment.

PMID- 14704042
TI  - Idiopathic thrombocytopenic purpura: better therapeutic responses of patients
      with B- or T-cell clonality than patients without clonality.
AB  - Results of recent studies of the pathogenesis of idiopathic thrombocytopenic
      purpura (ITP) have suggested activated helper T-cells drive B-lymphocytes to
      produce antibodies. Twenty-eight children and 85 adults with ITP entered this
      study. We performed polymerase chain reaction (PCR) using framework III variable
      region (V(H) FRIII)- and joining region (J(H))-specific primers to analyze
      immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell clonality. We
      used multiplex PCR to analyze T-cell receptor (TCR) gamma-chain gene
      rearrangement (TCRgamma GR) for T-cell clonality. We diagnosed 10 cases as acute
      ITP and 97 cases as chronic ITP. The IgH GR result was positive in 77.8% of the
      acute-form cases and in 58.8% of the chronic-form cases. The TCRgamma GR result
      was positive in 11.1% of the acute cases and in 10.6% of the chronic cases. There
      was no difference in frequency of clonality between the acute and chronic forms.
      After treatment the platelet count normalized in 81.8% (36/44) of the chronic ITP
      cases with B-cell clonality and in 88.9% (8/9) of the chronic ITP cases with T
      cell clonality, compared with a normalized platelet count in 46.2% (12/26) of the
      chronic ITP cases without clonality. The patients with T- or B-cell clonality
      appeared to have better therapeutic responses than patients without clonality. In
      conclusion, T- and B-cell clonality may play a positive role in determining
      therapeutic response.

PMID- 14704043
TI  - Clinical evaluation of a recombinant factor VIII preparation (Kogenate) in
      previously untreated patients with hemophilia A.
AB  - The safety and efficacy of a recombinant factor VIII (rFVIII) preparation
      (Kogenate) for the treatment of bleeding episodes was studied in previously
      untreated patients (PUPs) with severe, moderate, and mild hemophilia A. Patient
      peripheral blood samples taken at baseline and at 3, 6, 9, 12, 18, and 24 months
      after the first infusion were evaluated for FVIII inhibitor antibodies by the
      Bethesda assay, for antibodies formed against trace proteins derived from the
      rFVIII production process, and for general changes in laboratory test results.
      Samples for general laboratory testing were also drawn every 6 months after the
      first 24 months. Hemostatic efficacy was assessed by physicians, and adverse
      events were recorded throughout the study period. Forty-three PUPs (30 with
      FVIII:C <1%; 10 with FVIII:C 1%-5%; and 3 with FVIII:C >5%) aged 3 months to 32
      years were enrolled at 33 centers in Japan. Patients were studied for a mean of
      51 months (range, 11-80 months), and the mean exposure time was 83 days (range, 2
      571 days). The incidence of occurrence of FVIII inhibitors was 34.9% (high
      responders [> or = 10 Bethesda U/mL], 11.6%; low responders [0.5-<10 Bethesda
      U/mL], 23.3%). The median cumulative exposure time of inhibitor detection was 12
      days, indicating inhibitor development at an early stage after the start of
      infusion of this preparation. Hemostasis was achieved with a single dose of
      Kogenate in 94.8% of the 951 bleeding episodes recorded in the study. Transient
      increases in antibodies against baby hamster kidney proteins and antimouse
      immunoglobulin G were observed in 14.0% and 18.6% of patients, respectively. Anti
      rFVIII seroconversion was observed in 18.6% of patients and only in patients with
      inhibitor antibodies. Antibody responses to trace proteins were not correlated
      with drug-related adverse events with the exception of FVIII activity inhibition
      in PUPs with anti-rFVIII seroconversion. These data indicate that Kogenate is
      safe and effective for the treatment of bleeding in PUPs with hemophilia A.

PMID- 14704044
TI  - Third International Symposium on Myelodysplastic Syndromes in Childhood.
AB  - This article summarizes presentations from the Third International Symposium on
      Myelodysplastic Syndromes in Childhood, April 27-29, 2003, in Stresa, Italy.
      Topics included epidemiology, pathology, cytogenetics, molecular biology,
      pathophysiology, and treatment. Dr. Susanna Fenu was the Meeting Chair.

PMID- 14704045
TI  - Formation of multinary intermetallics from reduction of perovskites by aluminum
      flux: M(3)Au(6+)(x)()Al(26)Ti (M = Ca, Sr, Yb), a stuffed variant of the BaHg(11)
      type.
AB  - New intermetallic phases were synthesized by reacting oxidic perovskites and gold
      metal in aluminum flux. The combination of MTiO(3) (M = Ca, Sr, Ba) and Au metal
      in excess molten aluminum produces quaternary compounds M(3)Au(6+)(x)()Al(26)Ti
      with a stuffed BaHg(11) structure type. An analogue with M = Yb was also
      synthesized; it shows mixed valent behavior.

PMID- 14704046
TI  - Synthesis and characterization of a magnetic semiconductor Na(2)RuO(4) containing
      one-dimensional chains of Ru(6+).
AB  - A new ternary ruthenium oxide Na(2)RuO(4) was prepared and shown to crystallize
      with a new structure type. Single crystal X-ray diffraction measurements reveal
      that Na(2)RuO(4) consists of RuO(4) chains made up of RuO(5) trigonal bipyramids
      by sharing axial corners. Na(2)RuO(4) is a magnetic semiconductor with a variable
      range hopping behavior, and its molar magnetic susceptibility chi(mol) has a
      broad maximum at approximately 74 K. The derivative d(chi(mol).T)/dT exhibits a
      peak at 37.7 K which has been confirmed by heat capacity measurement to be due to
      long-range antiferromagnetic ordering.

PMID- 14704047
TI  - Coordinating anions: (phosphino)tetraphenylborate ligands as new reagents for
      synthesis.
AB  - Anionic, electron-releasing phosphines that incorporate a borate counteranion
      within the ligand framework are promising reagents for organometallic catalysis.
      This report describes the synthesis of a new class of monodentate tertiary
      phosphines built upon the commonly employed tetraphenylborate anion. These new
      phosphines are highly stable and strongly electron-releasing and readily
      coordinate transition metals. Moreover, they are promising reagents for
      catalysis, as demonstrated by their ability to promote the Suzuki cross-coupling
      of aryl chloride substrates.

PMID- 14704048
TI  - Synthesis of hybrid framework materials under "dry" hydrothermal conditions:
      crystal structure and magnetic properties of Mn(2)(H(2)PO(4))(2)(C(2)O(4)).
AB  - An exploration of the manganese oxalate-phosphoric acid-water system under
      hydrothermal conditions, and using "reagent" quantities only of water, has led to
      the isolation of a new mixed anion framework material
      Mn(2)(H(2)PO(4))(2)(C(2)O(4)). This material features continuous chains of cis
      edge-sharing MnO(6) octahedra, a motif which is unique among mixed phosphate
      oxalate materials identified so far. These octahedral chains are linked into a
      three-dimensional framework via corner-sharing with H(2)PO(4) tetrahedra, with
      oxalate ions acting as a bis-bidentate ligand in the third direction. Magnetic
      susceptibility studies show that this material may be modeled as an
      antiferromagnetic, S = (5)/(2) Heisenberg chain, with weaker coupling between the
      chains.

PMID- 14704049
TI  - Research on soluble metal sulfides: from polysulfido complexes to functional
      models for the hydrogenases.
AB  - Results from this laboratory are surveyed, emphasizing the synthesis of metal
      sulfides. Four themes are described. Continuing studies exploit the exothermic
      desulfurization of polysulfido complexes as a means to generate new clusters and
      rings. Illustrative inorganic rings prepared in this way include 1,5
      [L(2)M](2)(S(3))(2) and 1,4-[L(2)M](2)(S(2))(2), where L(2)M = CpRu(PPh(3)) and
      Cp(2)Ti. Fundamentally new clusters prepared in this project included the cubanes
      [(C(5)R(5))MS](4) for M = Ti, V, Ru, Ir. Associated redox studies led to the
      discovery of the phenomenon of mobile metal-metal bonds, as manifested in
      [Cp(4)Ir(4)S(4)](2+) wherein the localized Ir-Ir bond migrates over the six Ir- -
      -Ir edges of the cluster. Other desulfurization experiments led to the
      preparation of the reactive species Ir(II)(2)S(2)(PPh(3))(4) from [IrS(16)](3)(-)
      and the synthesis of the first high polymers of ferrocene, [(RC(5)H(3)S)(2)Fe](n)
      (n approximately 500). A second theme uncovered the useful role of donor solvents
      on the reaction of metals with sulfur. It was found that pyridine accelerates the
      low temperature conversion of Cu to crystalline CuS via the intermediacy of the
      cluster Cu(4)(S(5))(2)L(4). Related synthetic methodology led to a family of
      amine-stabilized zinc polysulfides, e.g. ZnS(6)(tmeda), an efficient sulfur
      transfer agent. A third theme explored the organic and organometallic chemistry
      of the tetrathiometalates. The sulfido analogue of OsO(4), ReS(4)(-) was shown to
      be broadly reactive toward unsaturated organic substrates such as alkenes,
      alkynes, nitriles, and isocyanides. The final and still emerging theme focuses on
      the preparation of functional and structural models for bio-organometallic
      reaction centers. Studies on models for the Fe-only hydrogenases began with the
      synthesis of the highly reducing species [Fe(2)(SR)(2)(CN)(2)(CO)(4)](2)(-) where
      (SR)(2) also includes the proposed azadithiolate cofactor HN(CH(2)S(-))(2).
      Systematic studies on the cyanide substitution process led to the preparation of
      [HFe(2)(SR)(2)(CN)(CO)(4)(PMe(3))], which efficiently catalyzes the reduction of
      protons to H(2). Work on the hydrogenases was expanded to include modeling of
      acetyl Co-A synthase, leading to the preparation of mixed valence Ni(2) models
      containing bound CO substrate.

PMID- 14704050
TI  - Exohedral multiple bonding in polyhedra. 2. Skeletal distortions in ring-stacked
      boranes.
AB  - Ring-stacked boranes of the B(10)H(10)(2)(-) and B(12)H(12)(2)(-) type, when
      substituted with lone pair bearing groups such as -O, -NH, and -S at the para
      positions, are theoretically shown to exhibit exopolyhedral multiple bonding on
      oxidation. Successive removal of two and four electrons from the parent B(n)H(n)(
      )(2)X(2) results in highly varied and intriguing skeletal deformations that are
      explained using fragment molecular theory.

PMID- 14704051
TI  - Novel triazole-bridged cadmium coordination polymers varying from zero- to three
      dimensionality.
AB  - Cadmium salts with different triazole ligands have led to a series of novel
      triazole-cadmium compounds varying from zero- to three-dimensionality.
      [Cd(2)(deatrz)(2)(H(2)O)Br(4)] (1) (deatrz = 3,5-diethyl-4-amino-1,2,4-triazole)
      is a zero-dimensional complex which uses a triazole ligand together with micro
      OH(2) as bridges to form a 1D chain via hydrogen-bonding contacts.
      [[Cd(3)(deatrz)(2)Cl(6)(H(2)O)(2)].2H(2)O](n) (2),
      [[Cd(dmtrz)Cl(2)].1.5H(2)O](n)(3) (dmtrz = 3,5-dimethyl-1,2,4-triazole), and
      [[Cd(3)(deatrz)(4)Cl(2)(SCN)(4)].2H(2)O](n)(4) are polymeric 1D chains. 2 and 4
      were constructed via trinuclear cadmium units bridged by triazole ligands and
      chloride atoms, while 3 consists of micro(2)-Cl, micro(3)-Cl, and triazole
      bridges, cross-linked by hydrogen bonding to give a 3D framework.
      [[Cd(3)(dmatrz)(4)(SCN)(6)]](n)(5) (dmatrz = 3,5-dimethyl-4-amino-1,2,4-triazole)
      shows a two-dimensional structure whose fundamental units are trinuclear metal
      cations bridged via triazole ligands. The complex [[Cd(dmtrz)(SCN)(2)]](n)(6) is
      the first three-dimensional example in N1,N2-didentate-bridged triazole-metal
      compounds. Six complexes exhibit six types of bridging modes of N1,N2-triazole in
      combination with single-atom bridges. 2, 4, and 5 are the unprecedented examples
      of polymeric chains and planes constructed via trinuclear metal ion clusters,
      whereas 3 is the first example of the micro(3)-Cl bridging mode in triazole-metal
      complexes. We have briefly discussed the variety of dimensionalities based on the
      tuning of different organic ligands and anions.

PMID- 14704052
TI  - Decomposition of a-type sandwiches. Synthesis and characterization of new
      polyoxometalates incorporating multiple d-electron-centered units.
AB  - The controlled decomposition of the sandwich-type polyoxometalates
      K(12)[(M(OH(2))(2))(3)(A-alpha-PW(9)O(34))(2)] (where M = Mn(II) or Co(II)) in
      0.5 M NaCl yields a new family of transition metal substituted POMs of the
      general formula [((MOH(2))M(2)PW(9)O(34))(2)(PW(6)O(26))](17)(-) (where M =
      Mn(II) (1Mn) or Co(II) (1Co)). The structure of 1Mn, determined by single-crystal
      X-ray diffraction (a = 17.4682(10) A, b = 22.3071(12) A, c = 35.1195(18) A, beta
      = 95.898(1) degrees, monoclinic, P2(1)/c, Z = 4, R(1) = 6.19%, based on 50264
      independent reflections), consists of two B-alpha
      (Mn(II)OH(2))Mn(II)(2)PW(9)O(34)(3)(-) units joined by a B-type hexavacant
      PW(6)O(26)(11)(-) fragment to form a C-shaped polyoxometalate. A low resolution X
      ray structure of the Co(II) analogue, 1Co, was also obtained. The UV-visible
      spectrum of 1Co shows the characteristic charge-transfer bands of
      polyoxometalates as well as a new Co-centered peak (560 nm, epsilon = 416 M(-)(1)
      cm(-)(1)) which appears at a higher wavelength relative to that exhibited by the
      parent A-type sandwich, K(12)[(Co(OH(2))(2))(3)(A-alpha-PW(9)O(34))(2)]. The
      methyltricaprylammonium salt of 1Mn is an effective catalyst for the H(2)O(2)
      based epoxidation of cis-cyclooctene, cyclohexene, and 1-hexene.

PMID- 14704053
TI  - Lead tetrakis(imidazolyl)borate solids: anion exchange, solvent intercalation,
      and self assembly of an organic anion.
AB  - The coordination polymer Pb[B(Im)(4)](NO(3))(xH(2)O), constructed by using sodium
      tetrakis(imidazolyl)borate and lead(II) nitrate solutions, is a layered material
      with the metal centers facing the interlayer spacing. As in naturally occurring
      layered minerals, this compound can readily undergo anion exchange and reversible
      intercalation of solvent water in the solid state with retention of
      crystallinity. We observed changes in solvent intercalation by (207)Pb solid
      state NMR (SSNMR) and thermogravimetric analysis (TGA). Stoichiometric exchange
      of (15)N nitrate for nitrate and iodide for nitrate is monitored by (15)N and
      (207)Pb SSNMR, and single crystals of the iodide-exchanged material Pb[B(Im)(4)]I
      were isolated. While the iodide compound can be obtained through facile exchange
      from the nitrate parent compound, the organic anion benzoate is placed in the
      interlayer spacing for nitrate under self-assembly conditions and forms an
      alternating monolayer in Pb[B(Im)(4)](C(6)H(5)COO)(0.5H(2)O). The ion exchange
      versus self-assembly behavior correlates with the structural differences in the
      three compounds. In both Pb[B(Im)(4)]I and Pb[B(Im)(4)](C(6)H(5)COO)(0.5H(2)O),
      the lead sites act as Lewis acids for the iodide and benzoate, respectively.

PMID- 14704054
TI  - Reactions of the tetrahedral clusters [MCo(3)(CO)(12)](-) (M = Ru, Fe) with
      functional mono- and diynes.
AB  - The tetrahedral cluster [RuCo(3)(CO)(12)](-) reacts with various alkynes,
      including the new PhCtbd1;CC(O)NHCH(2)Ctbd1;CH (L(1)()), to afford the butterfly
      clusters [RuCo(3)(CO)(10)(micro(4)-eta(2)-RC(2)R')](-) (1, R = R' = C(O)OMe; 2, R
      = H, R' = Ph; 3, R = H, R' = MeC=CH(2); 4, R = H, R' = CH(2)OCH(2)Ctbd1;CH; 5, R
      = H, R' = CH(2)NHC(O)Ctbd1;CPh), in which the ruthenium atom occupies a hinge
      position and the alkyne is coordinated in a micro(4)-eta(2) fashion. Reaction of
      the anions 1-3 with [Cu(NCMe)(4)]BF(4) led to selective loss of the 12e fragment
      Co(CO)(-) to form [RuCo(2)(CO)(9)(micro(3)-eta(2)-RC(2)R')] (6, R = R' = C(O)OMe;
      7, R = H, R' = Ph; 8, R = H, R' = MeC=CH(2)). To prepare functionalized RuCo(3)
      or FeCo(3) clusters that could be subsequently condensed with a silica matrix via
      the sol-gel method, we reacted [MCo(3)(CO)(12)](-) (M = Ru, Fe) with the alkyne
      PhCtbd1;CC(O)NH(CH(2))(3)Si(OMe)(3)(L(2)()) and obtained the butterfly clusters
      [MCo(3)(CO)(10)(micro(4)-eta(2)-PhC(2)C(O)NH(CH(2))(3)Si(OMe)(3))](-) 9 and 10,
      respectively. Air-stable [RuCo(3)(CO)(10)(micro(4)-eta(2)
      Me(3)SiC(2)Ctbd1;CSiMe(3))](-) (11) was obtained from 1,4
      bis(trimethylsilyl)butadiyne and reacted with [Cu(NCMe)(4)]BF(4) to give
      [RuCo(2)(CO)(9)(micro(3)-eta(2)-HC(2)Ctbd1;CSiMe(3))] (12), owing to partial
      ligand proto-desilylation, and not the expected [RuCo(2)(CO)(9)(micro(3)-eta(2)
      Me(3)SiC(2)Ctbd1;CSiMe(3))]. Reaction of 11 with [NO]BF(4) afforded, in addition
      to 12, [RuCo(3)(CO)(9)(NO)(micro(4)-eta(2)-Me(3)SiC(2)Ctbd1;CSiMe(3))] (13) owing
      to selective CO substitution on a wing-tip cobalt atom with NO. The thermal
      reaction of 11 with [AuCl(PPh(3))] led to replacement of a CO on Ru by the PPh(3)
      originating from [AuCl(PPh(3))] and afforded [RuCo(3)(CO)(9)(PPh(3))(micro(4)
      eta(2)-Me(3)SiC(2)Ctbd1;CSiMe(3))](-) (14), also obtained directly by reaction of
      11 with one equivalent of PPh(3). Proto-desilylation of 11 using TBAF/THF-H(2)O
      afforded [RuCo(3)(CO)(10)(micro(4)-eta(2)-Me(3)SiC(2)Ctbd1;CH)](-) (15) which, by
      Sonogashira coupling with 1,4-diiodobenzene, yielded the dicluster complex
      [[RuCo(3)(CO)(10)(micro(4)-eta(2)-Me(3)SiC(2)Ctbd1;C)]](2)C(6)H(4)](2)(-) (16).
      The crystal structures of NEt(4).3a, NEt(4).4a, 6, NEt(4).11b, NEt(4).14, and
      [N(n-Bu)(4)].15a have been determined by X-ray diffraction. Preliminary results
      indicate the potential of silica-tethered alkyne mixed-metal clusters, obtained
      by the sol-gel method, as precursors to bimetallic particles.

PMID- 14704055
TI  - Synthesis of Pt(dpk)Cl(4) and the reversible hydration to Pt(dpk-O-OH)Cl(3).H
      phenCl: X-ray, spectroscopic, and electrochemical characterization.
AB  - We report on the synthesis of a platinum(IV) compound containing a di-2-pyridyl
      ketone (dpk) ligand that is stable both in its anhydrous form [Pt(dpk)Cl(4)] (1)
      and in its hydrated form [Pt(dpk-O-OH)Cl(3)].H-phenCl (2). The crystal structure
      of the hydrated form shows that one of the hydroxide groups from the resulting
      gem-diol has undergone a cyclometalation/condensation reaction resulting in an
      oxygen atom directly coordinated to the Pt(IV) center and the formation of H
      phenCl. We correlate our physical data with predictions made by molecular
      modeling, and we propose an explanation for the unusual activity found for this
      dpk ketone. Spectroscopic and solubility studies are presented here, as well.
      Electrochemical studies of 1 indicate that it undergoes a highly irreversible
      reduction at a potential of about -0.45 V vs Ag(+)/Ag in CH(3)CN and that the
      irreversibility is likely due to an EC mechanism, the nature of which is
      currently under further investigation. Another distinct redox pair, apparently
      reversible, appears at a potential of about -1.1 V vs Ag(+)/Ag.

PMID- 14704056
TI  - Monomeric oxovanadium(IV) compounds of the general formula cis
      [V(IV)(=O)(X)(L(NN))(2)](+/0) [X = OH(-), Cl(-), SO(4)(2)(-) and L(NN) = 2,2'
      bipyridine (bipy) or 4,4'-disubstituted bipy].
AB  - Reaction of [V(IV)OCl(2)(THF)(2)] in aqueous solution with 2 equiv of AgBF(4) or
      AgSbF(6) and then with 2 equiv of 2,2'-bipyridine (bipy), 4,4'-di-tert-butyl-2,2'
      bipyridine (4,4'-dtbipy), or 4,4'-di-methyl-2,2'-bipyridine (4,4'-dmbipy) affords
      compounds of the general formula cis-[V(IV)O(OH)(L(NN))(2)]Y [where L(NN) = bipy,
      Y = BF(4)(-) (1), L(NN) = 4,4'-dtbipy, Y = BF(4)(-) (2.1.2H(2)O), L(NN) = 4,4'
      dmbipy, Y = BF(4)(-) (3.2H(2)O), and L(NN) = 4,4'-dtbipy, Y = SbF(6)(-) (4)].
      Sequential addition of 1 equiv of Ba(ClO(4))(2) and then of 2 equiv of bipy to an
      aqueous solution containing 1 equiv of V(IV)OSO(4).5H(2)O yields cis
      [V(IV)O(OH)(bipy)(2)]ClO(4) (5). The monomeric compounds 1-5 contain the cis
      [V(IV)O(OH)](+) structural unit. Reaction of 1 equiv of V(IV)OSO(4).5H(2)O in
      water and of 1 equiv of [V(IV)OCl(2)(THF)(2)] in ethanol with 2 equiv of bipy
      gives the compounds cis-[V(IV)O(OSO(3))(bipy)(2)].CH(3)OH.1.5H(2)O
      (6.CH(3)OH.1.5H(2)O) and cis-[V(IV)OCl(bipy)(2)]Cl (7), respectively, while
      reaction of 1 equiv of [V(IV)OCl(2)(THF)(2)] in CH(2)Cl(2) with 2 equiv of 4,4'
      dtbipy gives the compound cis-[V(IV)OCl(4,4'-dtbipy)(2)]Cl.0.5CH(2)Cl(2)
      (8.0.5CH(2)Cl(2)). Compounds cis-[V(IV)O(BF(4))(4,4'-dtbipy)(2)]BF(4) (9), cis
      [V(IV)O(BF(4))(4,4'-dmbipy)(2)]BF(4) (10), and cis-[V(IV)O(SbF(6))(4,4'
      dtbipy)(2)]SbF(6) (11) were synthesized by sequential addition of 2 equiv of 4,4'
      dtbipy or 4,4'-dmbipy and 2 equiv of AgBF(4) or AgSbF(6) to a dichloromethane
      solution containing 1 equiv of [V(IV)OCl(2)(THF)(2)]. The crystal structures of
      2.1.2H(2)O, 6.CH(3)OH.1.5H(2)O, and 8.0.5CH(2)Cl(2) were demonstrated by X-ray
      diffraction analysis. Crystal data are as follows: Compound 2.1.2H(2)O
      crystallizes in the orthorhombic space group Pbca with (at 298 K) a = 21.62(1) A,
      b = 13.33(1) A, c = 27.25(2) A, V = 7851(2) A(3), Z = 8. Compound
      6.CH(3)OH.1.5H(2)O crystallizes in the monoclinic space group P2(1)/a with (at
      298 K) a = 12.581(4) A, b = 14.204(5) A, c = 14.613(6) A, beta = 114.88(1)
      degrees, V = 2369(1), Z = 4. Compound 8.0.5CH(2)Cl(2) crystallizes in the
      orthorhombic space group Pca2(1) with (at 298 K) a = 23.072(2) A, b = 24.176(2)
      A, c = 13.676(1) A, V = 7628(2) A(3), Z = 8 with two crystallographically
      independent molecules per asymmetric unit. In addition to the synthesis and
      crystallographic studies, we report the optical, infrared, magnetic,
      conductivity, and CW EPR properties of these oxovanadium(IV) compounds as well as
      theoretical studies on [V(IV)O(bipy)(2)](2+) and [V(IV)OX(bipy)(2)](+/0) species
      (X = OH(-), SO(4)(2)(-), Cl(-)).

PMID- 14704057
TI  - Module-based assembly of copper(II) chloranilate compounds: syntheses, crystal
      structures, and magnetic properties of [[Cu(2)(CA)(terpy)(2)][Cu(CA)(2)]](n)()
      and [[Cu(2)(CA)(terpy)(2)(dmso)(2)][Cu(CA)(2)(dmso)(2)](EtOH)](n)(H(2)CA =
      chloranilic acid, terpy = 2,2':6',2' '-terpyridine, dmso = dimethyl sulfoxide).
AB  - Two new copper(II) compounds of chloranilate and 2,2':6',2' '-terpyridine have
      been synthesized, and the structures have been solved by the single-crystal X-ray
      diffraction method. The crystal structure of
      [[Cu(2)(CA)(terpy)(2)][Cu(CA)(2)]](n)(1), where H(2)CA = chloranilic acid and
      terpy = 2,2':6',2' '-terpyridine, consists of two modules, the dimer unit
      [Cu(2)(CA)(terpy)(2)](2+) and the anionic mononuclear unit [Cu(CA)(2)](2)(-),
      forming an alternated chain. The chain is stabilized by semicoordinating and
      additional but efficient secondary bonding interactions. The crystal structure of
      [[Cu(2)(CA)(terpy)(2)(dmso)(2)][Cu(CA)(2)(dmso)(2)](EtOH)](n)(2), where dmso =
      dimethyl sulfoxide, consists of solvent molecules and two discrete modules, the
      dimer unit [Cu(2)(CA)(terpy)(2)(dmso)(2)](2+) and the anionic mononuclear unit
      [Cu(CA)(2)(dmso)(2)](2)(-). The dimer units form a layer by secondary bonding
      interactions, and the monomer units and ethanol molecules are introduced between
      the layers. The magnetic properties of 1 and 2 have been investigated in the
      temperature range 2.0-300 K. A weak ferromagnetic interaction was observed in 1,
      J(a) = 2.36 cm(-)(1) and zJ(b) = -0.68 cm(-)(1) while no exchange coupling was
      observed in 2.

PMID- 14704058
TI  - Polynuclear manganese complexes with the dicarboxylate ligand m
      phenylenedipropionate: a hexanuclear mixed-valence (3Mn(III), 3Mn(IV)) complex.
AB  - The dicarboxylate group m-phenylenedipropionate (mpdp(2)(-)) has been used for
      the synthesis of four new Mn compounds of different nuclearities and oxidation
      states: [Mn(2)O(mpdp)(bpy)(2)(H(2)O)(MeCN)](ClO(4))(2) (3),
      [Mn(3)O(mpdp)(3)(py)(3)](ClO(4)) (4), [Mn(3)O(mpdp)(3)(py)(3)] (5), and
      [Mn(6)O(7)(mpdp)(3)(bpy)(3)](ClO(4)) (6). Compound 3 (2Mn(III)) contains a
      [Mn(2)(micro-O)](4+) core, whereas 5 (Mn(II), 2Mn(III)) and 4 (3Mn(III)) contain
      the [Mn(3)(micro(3)-O)](6+,7+) core, respectively. In all three compounds, the
      mpdp(2)(-) ligand is flexible enough to adopt the sites occupied by two
      monocarboxylates in structurally related compounds, without noticeable distortion
      of the cores. Variable-temperature magnetic susceptibility studies establish that
      3 and 5 have ground-state spin values of S = 0 and S = 1/2, respectively.
      Compound 6 is a highly unusual 3Mn(III), 3Mn(IV) trapped-valent compound, and it
      is also a new structural type, with six Mn atoms disposed in a distorted trigonal
      antiprismatic topology. Its electronic structure has been explored by variable
      temperature measurements of its dc magnetic susceptibility, magnetization vs
      field response, and EPR spectrum. The magnetic data indicate that it possesses an
      S = 3/2 ground state with an axial zero-field splitting parameter of D = -0.79
      cm(-)(1), and this conclusion is supported by the EPR data. The combined results
      demonstrate the ligating flexibility of the mpdp(2)(-) ligand and its usefulness
      in the synthesis of a variety of Mn(x) species.

PMID- 14704059
TI  - Higher order speciation effects on plutonium L(3) X-ray absorption near edge
      spectra.
AB  - Pu L(3) X-ray near edge absorption spectra for Pu(0-VII) are reported for more
      than 60 chalcogenides, chlorides, hydrates, hydroxides, nitrates, carbonates, oxy
      hydroxides, and other compounds both as solids and in solution, and substituted
      in zirconolite, perovskite, and borosilicate glass. This large database extends
      the known correlations between the energy and shape of these spectra from the
      usual association of the XANES with valence and site symmetry to higher order
      chemical effects. Because of the large number of compounds of these different
      types, a number of novel and unexpected behaviors are observed, such as effects
      resulting from the medium and disorder that can be as large as those from
      valence.

PMID- 14704060
TI  - Transient mixed-valence character of Re(I)(4)(CO)(12)(4,4'-bpy)(4)Cl(4).
AB  - This study addresses, in detail, the orbital nature and the extent of metal-metal
      communication in the lowest emitting triplet state of Re(4)(CO)(12)(4,4'
      bpy)(4)Cl(4) (where 4,4'-bpy = 4,4'-bipyridine) as well as the symmetry of the
      lowest (3)MLCT manifold in comparison to that of the ground state. All spectral
      evidence points to (1). a (3)MLCT excited manifold localized between a single
      Re(I) corner and an adjacent bridging ligand, (2). a transient mixed-valence
      state that is completely localized between a single transiently oxidized Re
      center and the adjacent metals, and (3). a second-order charge transfer from a
      localized transiently reduced bridging ligand to the adjacent Re(I) center to
      which it is attached, effectively lowering its oxidation state. The orbital
      nature of the lowest (3)MLCT manifold is fully corroborated by a molecular
      orbital diagram derived from quantum chemical modeling studies, while the
      existence of the localization, localized mixed valency, and second-order charge
      transfer rely on spectral evidence alone. This work makes use of low-temperature
      time-resolved infrared (TRIR) techniques as well as a luminescence study. Many of
      the nuances of the luminescence and TRIR data interpretation are extracted from
      statistical analysis and quantum chemical modeling studies. The relative
      concentrations of the dominant conformers that exist for Re(4)(CO)(12)(4,4'
      bpy)(4)Cl(4) have also been estimated from Boltzmann statistics.

PMID- 14704061
TI  - A reinterpretation of the magnetic properties of the mixed-valence (Nb(V)/Nb(IV))
      Zintl phase, Cs(9)Nb(2)As(6).
AB  - A new mixed-valent (Nb(V)/Nb(IV)) Zintl phase, Cs(9)Nb(2)As(6), has been prepared
      and characterized, recently (Gascoin, F.; Sevov, S. C. Inorg. Chem. 2002, 41,
      5920). Niobium is present in the form of isolated, edge-sharing tetrahedral,
      Nb(2)As(6)(9)(-) dimers. The reported magnetic susceptibility features a broad
      maximum at approximately 36 K which has been interpreted as the onset of long
      range antiferromagnetic order. Such a high transition temperature is difficult to
      understand as the compound is insulating and the interdimer Nb-Nb distance is 7.2
      A. It is shown here that the observed magnetic properties follow
      straightforwardly from a statistical occupation of the equivalent intradimer Nb
      sites by equal concentrations of Nb(IV)(4d(1), S = (1)/(2)) and Nb(V)(4d(0)).
      From this analysis the broad maximum arises from intradimer antiferromagnetic
      exchange with an exchange constant, J/k = -40 K, and there is no long-range
      magnetic order except, possibly, below 5 K.

PMID- 14704062
TI  - Structure and magnetism of the tetra-copper(II)-substituted heteropolyanion
      [Cu(4)K(2)(H(2)O)(8)(alpha-AsW(9)O(33))(2)](8-).
AB  - The novel heteropolyanion [Cu(4)K(2)(H(2)O)(8)(alpha-AsW(9)O(33))(2)](8)(-) (1)
      has been synthesized and characterized by IR spectroscopy, elemental analysis,
      and magnetic studies. Single-crystal X-ray analysis was carried out on
      [K(7)Na[Cu(4)K(2)(H(2)O)(6)(alpha-AsW(9)O(33))(2)].5.5H(2)O](n)(K(7)Na-1), which
      crystallizes in the tetragonal system, space group P42(1)m, with a = 16.705(4) A,
      b = 16.705(4) A, c = 13.956(5) A, and Z = 2. Interaction of the lacunary [alpha
      AsW(9)O(33)](9)(-) with Cu(2+) ions in neutral, aqueous medium leads to the
      formation of the dimeric polyoxoanion 1 in high yield. Polyanion 1 consists of
      two alpha-AsW(9)O(33) units joined by a cyclic arrangement of four Cu(2+) and two
      K(+) ions, resulting in a structure with C(2)(v)() symmetry. All copper ions have
      one terminal water molecule, resulting in square-pyramidal coordination geometry.
      Three of the copper ions are adjacent to each other and connected via two
      micro(3)-oxo bridges. EPR studies on K(7)Na-1 and also on
      Na(9)[Cu(3)Na(3)(H(2)O)(9)(alpha-AsW(9)O(33))(2)].26H(2)O (Na(9)-2) over 2-300 K
      yielded g values that are consistent with a square-pyramidal coordination around
      the copper(II) ions in 1 and 2. No hyperfine structure was observed due to the
      presence of strong spin exchange, but fine structure was observed for the excited
      (S(T) = 3/2) state of Na(9)-2 and the ground state (S(T) = 1) of K(7)Na-1. The
      zero-field (D) parameters have also been determined for these states,
      constituting a rare case wherein one observes EPR from both the ground and the
      excited states. Magnetic susceptibility data show that Na(9)-2 has
      antiferromagnetically coupled Cu(2+) ions, with J = -1.36 +/- 0.01 cm(-)(1),
      while K(7)Na-1 has both ferromagnetically and antiferromagnetically coupled
      Cu(2+) ions (J(1) = 2.78 +/- 0.13 cm(-)(1), J(2) = -1.35 +/- 0.02 cm(-)(1), and
      J(3) = -2.24 +/- 0.06 cm(-)(1)), and the ground-state total spins are S(T) = 1/2
      in Na(9)-2 and S(T) = 1 in K(7)Na-1.

PMID- 14704063
TI  - Structure and physical properties of [micro-tris(1,4-bis(tetrazol-1-yl)butane
      N4,N4')iron(II)] bis(hexafluorophosphate), a new Fe(II) spin-crossover compound
      with a three-dimensional threefold interlocked crystal lattice.
AB  - [micro-Tris(1,4-bis(tetrazol-1-yl)butane-N4,N4')iron(II)]
      bis(hexafluorophosphate), [Fe(btzb)(3)](PF(6))(2), crystallizes in a three
      dimensional 3-fold interlocked structure featuring a sharp two-step spin
      crossover behavior. The spin conversion takes place between 164 and 182 K showing
      a discontinuity at about T(1/2) = 174 K and a hysteresis of about 4 K between
      T(1/2) and the low-spin state. The spin transition has been independently
      followed by magnetic susceptibility measurements, (57)Fe-Mossbauer spectroscopy,
      and variable temperature far and midrange FTIR spectroscopy. The title compound
      crystallizes in the trigonal space group P3 (No. 147) with a unit cell content of
      one formula unit plus a small amount of disordered solvent. The lattice
      parameters were determined by X-ray diffraction at several temperatures between
      100 and 300 K. Complete crystal structures were resolved for 9 of these
      temperatures between 100 (only low spin, LS) and 300 K (only high spin, HS), Z =
      1 [Fe(btzb)(3)](PF(6))(2): 300 K (HS), a = 11.258(6) A, c = 8.948(6) A, V =
      982.2(10) A(3); 100 K (LS), a = 10.989(3) A, c = 8.702(2) A, V = 910.1(4) A(3).
      The molecular structure consists of octahedral coordinated iron(II) centers
      bridged by six N4,N4' coordinating bis(tetrazole) ligands to form three 3
      dimensional networks. Each of these three networks is symmetry related and
      interpenetrates each other within a unit cell to form the interlocked structure.
      The Fe-N bond lengths change between 1.993(1) A at 100 K in the LS state and
      2.193(2) A at 300 K in the HS state. The nearest Fe separation is along the c
      axis and identical with the lattice parameter c.

PMID- 14704064
TI  - Cyclotriphosphazene hydrazides as efficient multisite coordination ligands.
      eta(3)-fac-non-geminal-N(3) coordination of spiro
      N(3)P(3)[O(2)C(12)H(8)][N(Me)NH(2)](4) (L) in L(2)CoCl(3) and L(2)M(NO(3))(2) (M
      = Ni, Zn, Cd).
AB  - The cyclophosphazene tetrahydrazide spiro-N(3)P(3)[O(2)C(12)H(8)][N(Me)NH(2)](4)
      (L) functions as a multisite coordination ligand and affords L(2)CoCl(3).2CH(3)OH
      (4), L(2)Ni(NO(3))(2).2CHCl(3).2.5H(2)O (5), L(2)Zn(NO(3))(2).2CH(3)CN.2H(2)O
      (6), and L(2)Cd(NO(3))(2) (7). Each of the cyclophosphazene ligands that is
      involved in coordination to the metal functions as a non-geminal-N(3) donor
      coordinating through one ring nitrogen atom and two non-geminal-NH(2) nitrogen
      atoms. The coordination geometry around the metal ion in 4-6 is approximately
      octahedral while it is severely distorted in the case of 7.

PMID- 14704065
TI  - Preparation, characterization, and condensation of copper tellurolate clusters in
      the pores of periodic mesoporous silica MCM-41.
AB  - The copper-tellurolate cluster [(Cu(6)(TePh)(6)(PPh(2)Et)(5)] has been loaded
      into the pores of MCM-41 by solid-state impregnation techniques. It was found
      that the best loading conditions are 110 degrees C and 10(-)(3) Torr static
      vacuum. The resulting material was analyzed by powder X-ray diffraction (PXRD),
      nitrogen adsorption isotherms, thermogravimetric analysis (TGA), (31)P CP MAS NMR
      spectroscopy, and TEM. It was observed that loading is accompanied by loss of the
      phosphine shell, with retention of the copper-tellurium core. Condensation of the
      impregnated material may proceed thermally or photochemically. Thermal
      condensation results in the formation of Cu(2)Te nanoparticles as demonstrated by
      PXRD, and TEM data suggests that the process has taken place inside the pores of
      MCM-41. Photochemical condensation yields larger metal-chalcogen clusters in the
      pores as suggested by the result of UV-vis diffuse reflectance spectroscopy and
      TEM measurements.

PMID- 14704066
TI  - New 1- and 2-dimensional polymeric structures of cyanopyridine complexes of Ag(I)
      and Cu(I).
AB  - Polymeric transition metal chalcogenides have attracted much attention because of
      their possible unusual properties directly derived from their extended
      structures. The molecules n-cyanopyridine (n = 2, 3, and 4) and pyridine-3,4
      dicarbonitrile are found to function as bidentate or monodentate (only pyridine
      nitrogen donor atom) ligands in the coordination of silver(I) and copper(I) ions,
      respectively. The mode of coordination depends on the anion and the
      crystallization conditions and has been elucidated in all cases by single-crystal
      X-ray crystallography. We report here the syntheses, structural characterization,
      and electrical properties of six new polymers, [Ag(2)(2
      cyanopyridine)(2)(NO(3))(2)](n)(1), [Ag(4)(3
      cyanopyridine)(8)(SiF(6))(2)(H(2)O)(2)](n) (2), [Ag(3
      cyanopyridine)(2)(NO(3))](n)(3), [Ag(pyridine-3,4
      dicarbonitrile)(2)(NO(3))](n)(4), [Cu(I)(4-cyanopyridine)(2)(SCN)](n)(5), and
      [Cu(I)(pyridine-3,4-dicarbonitrile)(2)(SCN)](n)(6). Compounds 1 and 2 exhibit
      novel two-dimensional networks, while 3-6 have one-dimensional chain structures,
      in which 3 is a single-stranded helix. Room-temperature conductivities of 1, 2,
      4, and 6 have been measured and are 3.1 x 10(-)(7), 2.7 x 10(-)(7), 7.4 x 10(
      )(6), and 4.3 x 10(-)(5) S.cm(-)(1), respectively. The effect of temperature on
      the conductivities has been investigated.

PMID- 14704067
TI  - Anionic platinum complexes with 2-pyridylphosphines as ligands for rhodium:
      synthesis of zwitterionic Pt-Rh organometallic compounds.
AB  - Bimetallic zwitterionic platinum(II)-rhodium(I) complexes of the type
      [(C(6)F(5))(3)Pt(micro-PPy(n)Ph(3)(-)(n)Rh(CO)(2))] and [(C(6)F(5))(3)Pt(micro
      PPy(n)Ph(3)(-)(n)())Rh(diene))] (n = 2, 3; Py = 2-pyridyl) have been prepared.
      The P end of the bridging ligands (micro-PPy(n)Ph(3)(-)(n)) is always coordinated
      to the Pt center, while the N-donor ends chelate the Rh atom, giving
      metallacycles comparable to pyrazolylborate-Rh complexes. These metallacycles can
      adopt two conformations, either with the Pt complex in pseudoaxial position
      approaching the Rh center or with the Pt complex in a remote position. The
      preferred conformation depends on the steric hindrance at the rhodium center. In
      less sterically demanding Rh-carbonyl complexes the Pt moiety gets close to the
      Rh moiety as this brings closer the opposite charges of the zwitterion. For diene
      complexes mixtures of conformers are obtained. The X-ray structures of
      [(C(6)F(5))(3)Pt(micro-PPhPy(2))Rh(COD)] (COD = 1,5-cyclooctadiene) and
      [(C(6)F(5))(3)Pt(micro-PPhPy(2))Rh(CO)(2)] are reported.

PMID- 14704068
TI  - Synthesis and structures of new pyromellitate coordination polymers with
      piperazine as a ligand.
AB  - Two new coordination polymers of the pyromellitic acid,
      [Zn(2)(H(2)O)(C(10)H(2)O(8))(C(4)N(2)H(8))]( infinity ), I, and
      [Cd(4)(H(2)O)(2)(C(10)H(2)O(8))(2)(C(4)N(2)H(8))(3)]( infinity ), II, have been
      prepared employing hydrothermal methods in the presence of piperazine. The
      structures have three-dimensional connectivity involving both the carboxylate and
      the amine molecule. The amine molecule acts as a ligand connecting two different
      metal centers giving rise to a simple dimer in I, and a two-dimensional layer
      structure in II. There are two types of pyromellitates in I and only one type in
      II. Of the two types of acids in I, acid-1 has all the oxygen atoms connected to
      Zn with monodendate connectivity and acid-2 has only four monodendate
      connectivity and possesses four terminal C-O linkage. In II, two of the
      carboxylates have bidendate connectivity and the other two have monodendate
      connectivity and possess one terminal C-O bond. The projection of the bound amine
      molecules, in II, into the large elliptical channels is noteworthy. These amine
      molecules may be amenable for chemical manipulations. Both the coordination
      polymers exhibit photoluminescence at room temperature, the main emission being
      at 380 and 410 nm, respectively, for I and II, which is due to the ligand-to
      metal charger transfer (LMCT).

PMID- 14704070
TI  - A convenient route to lanthanide triiodide THF solvates. Crystal structures of
      LnI(3)(THF)(4) [Ln = Pr] and LnI(3)(THF)(3.5) [Ln = Nd, Gd, Y].
AB  - The reaction between 1.5 equiv of elemental iodine and rare earth metals in
      powder form in THF at room temperature gives the rare earth triiodides
      LnI(3)(THF)(n)() in good yields. Purification by Soxhlet extraction of the crude
      solids with THF reliably gives the THF adducts LnI(3)(THF)(4) [Ln = La, Pr] and
      LnI(3)(THF)(3.5) [Ln = Nd, Sm, Gd, Dy, Er, Tm, Y] as microcrystalline solids. X
      ray crystallography reveals that the early, larger lanthanide iodide
      PrI(3)(THF)(4) crystallizes as discrete molecules having a pentagonal bipyramidal
      structure, whereas the later, smaller lanthanide iodides LnI(3)(THF)(3.5) [Ln =
      Nd, Gd, Y] crystallize as solvent-separated ion pairs
      [LnI(2)(THF)(5)][LnI(4)(THF)(2)] in which the cations adopt a pentagonal
      bipyramidal geometry and the anions adopt an octahedral geometry in the solid
      state.

PMID- 14704069
TI  - Coordination chemistry of the antitumor metallocene molybdocene dichloride with
      biological ligands.
AB  - The relative affinity of molybdocene dichloride (Cp(2)MoCl(2)) for the thiol,
      amino, carboxylate, phosphate(O) and heterocyclic(N) donor ligands present in
      amino acids and nucleotides, has been studied in aqueous solutions at pH 2-7,
      using (1)H, (13)C and (31)P NMR spectroscopy. Molybdocene dichloride forms the
      highly water soluble, air-stable complexes Cp(2)Mo(Cys)(2) and Cp(2)Mo(GS)(2)
      with cysteine and glutathione respectively, via coordination of the deprotonated
      thiol groups. While coordination to the imidazole nitrogen in histidine was
      observed, no evidence for coordination of the amino or carboxylate groups in the
      amino acids cysteine, histidine, alanine or lysine to Cp(2)MoCl(2) was detected.
      Competition experiments with dAMP, ribose monophosphate and histidine showed
      preferential coordination to the cysteine thiol over the phosphate(O) and
      heterocyclic(N) groups. Cp(2)Mo(Cys)(2) is stable in the presence of excess dAMP
      or ribose monophosphate and Cys displaces coordinated histidine, dAMP or ribose
      monophosphate to give Cp(2)Mo(Cys)(2). These results provide further evidence
      against interaction with DNA as the key interaction that is related to the
      antitumor activity of molybdocene dichloride. The implications of these results
      for the biological activity of the antitumor metallocene and the likely species
      formed in vivo are discussed.

PMID- 14704071
TI  - Synthesis and characterization of Mo(6) chalcobromides and cyano-substituted
      compounds built from a novel [(Mo(6)Br(i)(6)Y(i)(2))L(a)(6)](n)()(-) discrete
      cluster unit (Y(i) = S or Se and L(a) = Br or CN).
AB  - The syntheses, crystal structures determined by single-crystal X-ray diffraction,
      and characterizations of new Mo(6) cluster chalcobromides and cyano-substituted
      compounds with 24 valence electrons per Mo(6) cluster (VEC = 24), are presented
      in this work. The structures of Cs(4)Mo(6)Br(12)S(2) and Cs(4)Mo(6)Br(12)Se(2)
      prepared by solid state routes are based on the novel
      [(Mo(6)Br(i)(6)Y(i)(2))Br(a)(6)](4)(-) (Y = S, Se) discrete units in which two
      chalcogen and six bromine ligands randomly occupy the inner positions, while the
      six apical ones are fully occupied by bromine atoms. The interaction of these two
      compounds with aqueous KCN solution results in apical ligand exchange giving the
      two first Mo(6) cyano-chalcohalides:
      Cs(0.4)K(0.6)(Et(4)N)(11)[(Mo(6)Br(6)S(2))(CN)(6)](3).16H(2)O and
      Cs(0.4)K(0.6)(Et(4)N)(11)[(Mo(6)Br(6)Se(2))(CN)(6)](3).16H(2)O. Their crystal
      structures, built from the original [(Mo(6)Br(i)(6)Y(i)(2))(CN)(a)(6)](4)(-)
      discrete units, will be compared to those of the two solid state precursors and
      other previously reported Mo(6) cluster compounds. Their redox properties and
      (77)Se NMR characterizations will be presented. Crystal data:
      Cs(4)Mo(6)Br(12)S(2), orthorhombic, Pbca (No. 61), a = 11.511(5) A, b = 18.772(5)
      A, c = 28.381 A (5), Z = 8; Cs(4)Mo(6)Br(12)Se(2), Pbca (No. 61), a = 11.6237(1)
      A, b = 18.9447(1) A, c = 28.4874(1) A, Z = 8;
      Cs(0.4)K(0.6)(Et(4)N)(11)[(Mo(6)Br(6)S(2))(CN)(6)](3).16H(2)O, Pm-3m (No. 221), a
      = 17.1969(4) A, Z = 1;
      Cs(0.4)K(0.6)(Et(4)N)(11)[(Mo(6)Br(6)Se(2))(CN)(6)](3).16H(2)O, Pm-3m (No. 221),
      a = 17.235(5) A, Z = 1.

PMID- 14704072
TI  - Cooperative spin crossover and order-disorder phenomena in a mononuclear compound
      [Fe(DAPP)(abpt)](ClO(4))(2) [DAPP = [bis(3-aminopropyl)(2-pyridylmethyl)amine],
      abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole].
AB  - The synthesis and detailed characterization of the new spin crossover mononuclear
      complex [Fe(II)(DAPP)(abpt)](ClO(4))(2), where DAPP = [bis(3-aminopropyl)(2
      pyridylmethyl)amine] and abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole, are
      reported. Variable-temperature magnetic susceptibility measurements and Mossbauer
      spectroscopy have revealed the occurrence of an abrupt spin transition with a
      hysteresis loop. The hysteresis width derived from magnetic susceptibility
      measurements is 10 K, the transition being centered at T(c) downward arrow = 171
      K for decreasing and T(c) upward arrow = 181 K for increasing temperatures. The
      crystal structure was resolved in the high-spin (293 and 183 K) and low-spin (123
      K) states. Both spin-state structures belong to the monoclinic space group
      P2(1)/n (Z = 4). The thermal spin transition is accompanied by the shortening of
      the mean Fe-N distances by 0.177 A. The two main structural characteristics of
      [Fe(DAPP)(abpt)](ClO(4))(2) are a branched network of intermolecular links in the
      crystal lattice and the occurrence of two types of order-disorder transitions (in
      the DAPP ligand and in the perchlorate anions) accompanying the thermal spin
      change. These features are discussed relative to the magnetic properties of the
      complex. The electronic structure calculations show that the structural disorder
      in the DAPP ligand modulates the energy gap between the HS and LS states. In line
      with previous studies, the order-disorder phenomena and the spin transition in
      [Fe(DAPP)(abpt)](ClO(4))(2) are found to be interrelated.

PMID- 14704073
TI  - Novel lanthanide coordination polymers with a flexible disulfoxide ligand, 1,2
      bis(ethylsulfinyl)ethane: structures, stereochemistry, and the influences of
      counteranions on the framework formations.
AB  - The reactions of meso-1,2-bis(ethylsulfinyl)ethane (meso-L) with Ln(ClO(4))(3)
      [Ln(NO(3))(3) or Ln(NCS)(3)] in MeOH and CHCl(3) gave a series of new lanthanide
      coordination polymers, [[Ln(micro-meso-L)(rac-L)(2)(CH(3)OH)(2)](ClO(4))(3)](n)
      [Ln: La (1), Nd (2), Eu (3), Gd (4), Tb (5), Dy (6), and Yb (7)], [Yb(micro-meso
      L)(1.5)(NO(3))(3)](n) (8), and [La(micro-meso-L)(2.5)(NCS)(3)](n) (9). All the
      structures were established by single-crystal X-ray diffraction. Complexes 1-7
      are isostructural with infinite single micro-chain structure, in which the L
      ligands take two kinds of coordination modes: bidentate chelating and bis
      monodentate bridging. Six sulfur atoms of the sulfoxide groups around each
      Ln(III) center adopt alternatively the same R or S configuration in the chain. In
      addition, the configuration change of partial ligands occurred from the meso to
      the rac form when reacting with Ln(ClO(4))(3). To our knowledge, this is the
      first example of disulfoxide complexes with two kinds of coordination modes and
      three kinds of configurations (R,R, S,S, and R,S) occurring simultaneously in the
      same complex. 8 exhibits single-double bridging chain structure, in which
      dinuclear macrometallacycles formed through bridging two Yb(III) by two meso-L
      ligands are further linked by another meso-L ligand. In 9 each La(III) ion is
      linked to five other La(III) ions by five meso-L ligands to form a 5-connected 2
      D (3/4,5) network containing two types of macrometallacyclic arrays:
      quadrilateral and triangle grids. The structural differences among 1-7, 8, and 9
      show that counteranions play important roles in the framework formation of such
      coordination polymers. In addition, the luminescent properties of 3 and 5 were
      also investigated.

PMID- 14704074
TI  - Crystal structure and spectroscopic study of novel two- and three-dimensional
      photoluminescent Eu(III)-adipate compounds.
AB  - Two new photoluminescent compounds with the formulas of
      [Eu(2)(adipate)(3)(H(2)O)].H(2)O (1) and [Eu(2)(adipate)(3)(4H(2)O)] (2) were
      synthesized by using Eu(III) chloride and adipic acid under hydrothermal reaction
      conditions in aqueous solution. Compound 1, a 3-D layered framework, possesses
      infinite Eu-O-Eu polyhedral chains and self-assembled adipate ligands between Eu
      O layers. Compound 2 has dimeric Eu(2)O(16) units interconnected by adipate
      ligand, resulting in 2-D open frameworks with a cavity among the ligands. Crystal
      data 1: monoclinic space group C2/c, with a = 14.2486(12) A, b = 8.2733(7) A, c =
      39.298(2) A, beta = 99.530(6) degrees, and Z = 8. 2: monoclinic space group
      P2(1)/c, with a = 11.661(4) A, b = 14.011(3) A, c = 9.013(4) A, beta = 110.87(3)
      degrees, and Z = 2. The ligand conformations of two Eu(III)-adipate (1 and 2)
      compounds present anti/anti/anti, gauche/anti/gauche, and intermediate forms.
      Both compounds 1 and 2 showed strong red luminescence upon excitation, and their
      luminescence decay involves the multiphonon relaxation mechanism.

PMID- 14704075
TI  - Synthesis of new porphyrins with peripheral conjugated chelates and their use for
      the preparation of porphyrin dimers linked by metal ions.
AB  - This article describes the preparation of several new porphyrins bearing
      chelating peripheral groups fully conjugated with the macrocyclic pi-system.
      Treatment of a 2-nitro-meso-tetraarylporphyrin with phosphite gave a cyclic
      enamine, whose formylation gave an enaminoaldehyde. The thio analogue was
      obtained on treatment with Lawesson's reagent. The same reagent was also used to
      obtain the isomeric thioenaminoketone chelates. A enaminoketone ligand was
      prepared from a porphyrinic pyrrolone. All these ligands, as internal nickel
      complexes, could be metalated with palladium to yield porphyrinic dimers. The
      dimers obtained from enaminoketones and thioketones show a trans geometry, while
      in the enaminoaldehyde and -thioaldehyde series the cis isomer is
      thermodynamically favored. The bathochromic shifts of the electronic spectra of
      the aldehyde-derived dimers illustrate the strong electronic effect of peripheral
      metalation and dimerization. However, in the case of the pyrrolone-derived
      ligand, opposite effects were observed, due to partial reconstitution of the
      porphyrin chromophore on complexation. As with the dimers derived from
      enaminoketones, the dimers derived from the new ligands show typical splitting
      (up to 190 mV) of the electrochemical waves confirming large porphyrin-porphyrin
      interactions.

PMID- 14704076
TI  - Oxyl radical required for o-o bond formation in synthetic Mn-catalyst.
AB  - DFT calculations using the B3LYP functional support the suggestion that the
      [(terpy)(H(2)O)Mn(IV)(micro-O)(2)Mn(III)(H(2)O)(terpy)](3+) (terpy=2,2':6,2' '
      terpyridine) complex functions as a synthetic O(2) catalyst. The calculated
      barrier for O-O bond formation with water is 23 kcal/mol. In this complex, as
      well as in models of the oxygen evolving complex in PSII, the active species is a
      Mn(IV)-oxyl radical. From comparisons with inactive Mn(V)-oxo complexes, it is
      proposed that radical formation is actually a requirement for O(2) formation
      activity in Mn-complexes.

PMID- 14704077
TI  - Synthesis and group 4 complexes of tris(pyrrolyl-alpha-methyl)amine.
AB  - The tetradentate, trianionic ligand tris(pyrrolyl-alpha-methyl)amine (H(3)tpa) is
      available in 84% yield in a single step by a triple Mannich reaction involving 3
      equiv of pyrrole, 3 equiv of formaldehyde, and ammonium chloride. The new ligand
      is readily placed on titanium by transamination on Ti(NMe(2))(4), which generates
      Ti(NMe(2))(tpa) (1) in 73% yield. Treating 1 with 1 equiv of 1,3-dimethyl-2
      iminoimidazolidine (H-imd) in toluene provided a rare example of a titanium 2
      iminoimidazolidinide, which displays some interesting structural features. Of
      note is the Ti-N(imd) distance of 1.768(2) A, a typical Ti-N double to triple
      bond distance. Reaction of Zr(NMe(2))(4) with H(3)tpa gave a complex of variable
      composition, probably varying in the amount of labile dimethylamine retained.
      However, stable discreet compounds were available by addition of THF, pyridine,
      or 4,4'-di-tert-butyl-2,2'-bipyridine (Bu(t)bpy) to in situ generated
      Zr(NMe(2))(NHMe(2))(x)(tpa). Three chloro zirconium complexes were generated
      using three different strategies. Treating Zr(tpa)(NMe(2))(Bu(t)bpy) (5) with
      ClSiMe(3) afforded Zr(tpa)(Cl)(Bu(t)bpy) (6) in 92% yield. Reaction of Li(3)tpa
      with ZrCl(4)(THF)(2) in THF gave a 72% yield of ZrCl(tpa)(THF)(2) (7). In
      addition, treatment of ZrCl(NMe(2))(3) with H(3)tpa cleanly generated
      ZrCl(NHMe(2))(2)(tpa) (8) in 95% yield. An organometallic zirconium complex was
      generated on treatment of 6 with LiCtbd1;CPh; alkynyl
      Zr(Ctbd1;CPh)(tpa)(Bu(t)bpy) (9) was isolated in 62% yield. 1, Ti(imd)(tpa) (2),
      6, and 9 were characterized by X-ray diffraction.

PMID- 14704078
TI  - Synthesis and structure of Ca(18)Li(5)In(25.07): a novel intergrowth of Li
      centered in(12) icosahedral clusters and electron-precise Zintl layers.
AB  - A new ternary polar intermetallic, Ca(18)Li(5)In(25.07), was obtained from high
      temperature reactions of the elements in welded Nb tubes. Its crystal structure,
      established by single-crystal X-ray diffraction, was found to crystallize in the
      orthorhombic space group Cmmm (No. 65). Unit cell parameters are a = 9.9151(6) A,
      b = 26.432(2) A, and c = 10.2116(6) A; Z = 2. The structure of
      Ca(18)Li(5)In(25.07) features two distinct types of indium anionic layers. An
      "electron-deficient" layer is made up of Li-centered In(12) icosahedra that are
      interconnected by bridging planar In(4) units and In atoms. A second In(3)(5-)
      layer is an electron-precise Zintl layer formed by fused four-, five-, and six
      membered rings of three- and four-bonded indium atoms. The two distinct layers
      are alternately stacked and linked into a complex three-dimensional network.
      Vacancies are observed to occur only at the In(12) icosahedral and the bridging
      indium units within the "electron-deficient" layers. Magnetic property
      measurements indicate that Ca(18)Li(5)In(25.07) exhibits temperature-independent
      paramagnetism consistent with metallic behavior. Band structure calculations were
      performed to elucidate the role of defects and vacancies in the electronic
      structure of the electron-deficient "metallic" Zintl phase.

PMID- 14704079
TI  - Interaction of palladium(II) and platinum(II) complexes with microperoxidase-11
      studied by electrospray mass spectrometry and MS/MS analysis.
AB  - Interactions of cis-[Pd(en)(H(2)O)(2)](2+) (en, ethylenediamine) and cis
      [Pt(NH(3))(2)(H(2)O)(2)](2+) with microperoxidase-11 (MP-11) in a molar ratio of
      1:1 or 2:1 at pH 1.4 were investigated via electrospray mass spectrometry and
      MS/MS analysis at room temperature and at 40 degrees C with an incubation time of
      2 or 3 days. The composition of the Pd(II)- and Pt(II)-anchored MP-11 was
      confirmed on the basis of the precise molecular mass and the simulated isotope
      distribution pattern. MS/MS analysis revealed that the Pd(II) center anchored to
      the side chain of Cys7 as Pd(II) and MP-11 were mixed in an equimolar ratio and
      to side chains of Cys7 and Cys4 as Pd(II) and MP-11 mixed in a 2:1 molar ratio.
      When Pt(II) and MP-11 were mixed in a 2:1 molar ratio, Pt(II) first anchored to
      the side chain of Cys7, and then to the side chain of Cys4 with time. The initial
      coordination of Pd(II) and Pt(II) to the side chain of Cys7 is the essential step
      for the Pd(II)- and Pt(II)-promoted cleavage of the His8-Thr9 bond in MP-11.
      These results support the hypothesis that the Pd(II)-mediated cleavage of the
      His18-Thr19 bond in cytochorome c is due to the identical binding mode.

PMID- 14704080
TI  - A DFT study of model complexes of zinc hydrolases and their inhibition by
      hydroxamic acids.
AB  - DFT calculations carried out on zinc acetate and zinc hydroxamates using the
      Hartree-Fock and B3LYP methods with the 6-311+G basis set give a series of stable
      pseudotetrahedral chelates (ZnL(2)) (L = OAc, FA, AA, NMeAA, GA, SA). Addition of
      a water molecule to these chelates gives the hydrates, ZnL(2).H(2)O, which in all
      cases are energetically more stable than the corresponding chelate. Hydrates
      formed from O,O coordinated hydroxamate species with a five-membered chelate ring
      contain water molecules occupying vacant coordination sites of the zinc atom. In
      contrast, those formed from zinc chelates with four-membered chelate rings
      contain a water molecule inserted into the chelate ring to give a six-membered
      ring in which one hydrogen of the water molecule is H-bonded to an oxygen atom of
      the zinc chelate with the water oxygen strongly bonded to the zinc. A slight
      lengthening of the H-bonded O-H bond suggests incipient hydroxide activation of
      water by zinc. In contrast, the O,O bonded hydroxamates do not incorporate water
      into the chelate ring nor activate the water in accordance with the ability of
      hydroxamic acids to inhibit zinc containing metalloenzymes.

PMID- 14704081
TI  - Design aspects for the development of mixed-metal supramolecular complexes
      capable of visible light induced photocleavage of DNA.
AB  - Mixed-metal supramolecular complexes that couple ruthenium or osmium based light
      absorbers to a central rhodium(III) core have been designed which photocleave DNA
      upon irradiation with visible light. The complexes
      [[(bpy)(2)Ru(dpp)](2)RhCl(2)](PF(6))(5), [[(bpy)(2)Os(dpp)](2)RhCl(2)](PF(6))(5),
      and [[(tpy)RuCl(dpp)](2)RhCl(2)](PF(6))(3), where bpy = 2,2'-bipyridine, tpy =
      2,2':6',2' '-terpyridine, and dpp = 2,3-bis(2-pyridyl)pyrazine, all exhibit
      intense metal to ligand charge transfer (MLCT) based transitions in the visible
      but possess lower lying metal to metal charge transfer (MMCT) excited states.
      These supramolecular complexes with low lying MMCT states photocleave DNA when
      excited into their intense MLCT transitions. Structurally similar complexes
      without this low lying MMCT state do not exhibit DNA photocleavage, establishing
      the role of this MMCT state in the DNA photocleavage event. Design considerations
      necessary to produce functional DNA photocleavage agents are presented herein.

PMID- 14704082
TI  - Mechanism of the axial ligand substitution reactions on the head-to-tail alpha
      pyridonato-bridged cis-diammineplatinum(III) dinuclear complex with olefins.
AB  - Reactions of the head-to-tail alpha-pyridonato-bridged cis-diammineplatinum(III)
      dinuclear complex having equivalent two platinum atoms, Pt(N(3)O), with p
      styrenesulfonate and 4-penten-1-ol were studied kinetically. Under the pseudo
      first-order reaction conditions in which the concentration of the Pt(III)
      dinuclear complex is much smaller than that of olefin, a consecutive basically
      four-step reaction was observed for the reaction with p-styrenesulfonate, but for
      the reaction with 4-penten-1-ol, the reaction was three step. The olefin pi
      coordinates to one of the two equivalent Pt atoms in the first step (step 1),
      followed by the second pi-coordination of another olefin molecule to the other Pt
      atom (step 2). In the next step (step 3), the nucleophilic attack of water to the
      first pi-coordinated olefin initiates its pi-sigma bond conversion on the Pt
      atom, and the second pi-bonding olefin molecule on the other Pt atom is released.
      Finally, dissociation of the alkyl group on the Pt(N(3)O) and reduction of the
      Pt(III) dinuclear complex to the Pt(II) dinuclear complex occur (step 4). The
      first water substitution with olefin (step 1) consists of two paths, the reaction
      of the diaqua dimer complex (path a) and the reaction of the aquahydroxo dimer
      complex (path b), whereas the second substitution (step 2) proceeds through three
      reaction paths: the normal path of the direct substitution of H(2)O (path c), the
      path of the coordinated OH(-) substitution (path d), and the path via the
      coordinatively unsaturated five-coordinate intermediate (path e). The reaction
      with p-styrenesulfonate proceeds through paths c, d, and e, whereas the reaction
      with 4-penten-1-ol proceeds through paths c and d. The third step (step 3) for
      the reaction with p-styrenesulfonate involves the coordinatively unsaturated
      intermediate, but that for the 4-pentene reaction does not. The reactivities of
      the HH dimer and HT dimer with olefins are compared and discussed.

PMID- 14704083
TI  - A facile route to bimetallic ruthenium dipyridophenazine complexes.
AB  - Using achiral coordinatively unsaturated metal complex building-blocks, the two
      step synthesis of a bimetallic complex containing independent [Ru(II)dppz] units
      tethered together by a linking 4,4'dipyridyl-1,5-pentane ligand is reported.
      Photophysical studies on this prototype system indicate that the characteristic
      luminescence of the [Ru(II)dppz] moieties is perturbed by self-quenching
      processes. Preliminary binding studies on the complex with natural and synthetic
      duplex DNA is reported. Luminescence and calorimetric titrations reveal that the
      complex does not show enhanced binding affinity with respect to analogous
      monometallic complexes. This result is interpreted by a consideration of the
      length and rigidity of the linker employed in the complex.

PMID- 14704084
TI  - Solution structures of chromium(VI) complexes with glutathione and model thiols.
AB  - Chromium(VI) complexes of the most abundant biological reductant, glutathione
      (gamma-Glu-Cys-Gly, I), are among the likely initial reactive intermediates
      formed during the cellular metabolism of carcinogenic and genotoxic Cr(VI).
      Detailed structural characterization of such complexes in solutions has been
      performed by a combination of X-ray absorption fine structure (XAFS) and X-ray
      absorption near-edge structure (XANES) spectroscopies, electrospray mass
      spectrometry (ESMS), UV-vis spectroscopy, and kinetic studies. The Cr(VI)
      complexes of two model thiols, N-acetyl-2-mercaptoethylamine (II) and 4
      bromobenzenethiol (III), were used for comparison. The Cr(VI)-thiolato complexes
      were generated quantitatively in weakly acidic aqueous solutions (for I and II)
      or in DMF solutions (for II) or isolated as a pure solid (for III). Contrary to
      some claims in the literature, no evidence was found for the formation of
      relatively stable Cr(IV) intermediates during the reactions of Cr(VI) with I in
      acidic aqueous solutions. The Cr(VI) complexes of I-III exist as tetrahedral
      [CrO(3)(SR)](-) (IVa) species in the solid state, in solutions of aprotic
      solvents such as DMF, or in the gas phase (under ESMS conditions). In aqueous or
      alcohol solutions, reversible addition of a solvent molecule occurs, with the
      formation of five-coordinate species, [CrO(3)(SR)L](-) (IVb, probably of a
      trigonal bipyramidal structure, L = H(2)O or MeOH), with a Cr-L bond length of
      1.97(1) A (determined by XAFS data modeling). Complex IVb (L = H(2)O) is also
      formed (in an equilibrium mixture with [CrO(4)](2)(-)) at the first stage of
      reduction of Cr(VI) by I in neutral aqueous solutions (as shown by global kinetic
      analysis of time-dependent UV-vis spectra). This is the first observation of a
      reversible ligand addition reaction in Cr(VI) complexes. The formation of IVb
      (rather than IVa, as thought before) during the reactions of Cr(VI) with I in
      aqueous solutions is likely to be important for the reactivity of Cr(VI) in
      cellular media, including DNA and protein damage and inhibition of protein
      tyrosine phosphatases.

PMID- 14704085
TI  - Synthesis, characterization, and crystal structures of three new divalent metal
      carboxylate-sulfonates with a layered and one-dimensional structure.
AB  - Hydrothermal reactions of 5-sulfoisophthalic acid (HO(3)SC(6)H(3)-1,3
      (CO(2)H)(2), H(3)L) with M(II) carbonate (or oxide) and 4,4'-bipyridine (4,4'
      bipy) (or 2,2'-bipyridine, 2,2'-bipy) resulted in three new metal carboxylate
      sulfonate hybrids, namely, [CdL(H-4,4'-bipy)] (1) and [Cd(3)L(2)(2,2
      bipy)(4)(H(2)O)(2)].2H(2)O (2) with layered structures and [ZnL(H-4,4'
      bipy)(H(2)O)].2H(2)O (3), whose structure features a one-dimensional double
      chain. The cadmium(II) ion in complex 1 is seven-coordinated by five carboxylate
      oxygen atoms and one sulfonate oxygen atom from four ligands and a unidentate
      4,4'-bipyridine. The interconnection of the cadmium(II) ions through bridging
      carboxylate-sulfonate ligands resulted in the formation of a <002> double layer
      with the bipyridyl rings orientated toward the interlayer space. Complex 2 has a
      different layered structure. Cd(1) is seven-coordinated by two bidentate
      chelating carboxylate groups from two ligands, a bidentate chelating 2,2'-bipy
      and an aqua ligand, and Cd(2) is octahedrally coordinated by two bidentate
      chelating 2,2'-bipy's, a sulfonate oxygen, and an aqua ligand. The coordination
      geometry around Cd(3) is similar to that of Cd(1) with the aqua ligand being
      replaced by an oxygen atom from the sulfonate group. The carboxylate-sulfonate
      ligand acts as pentadentate ligand, bridging with three cadmium(II) ions. The
      bridging of cadmium(II) ions through the carboxylate-sulfonate ligands resulted
      in the formation of <006> and <003> layers; the 2,2'-bipy molecules and
      [Cd(2)(2,2'-bipy)(2)(H(2)O)] cations are orientated to the interlayer space.
      Complex 3 features a 1D metal carboxylate-sulfonate double chain along the
      diagonal of the a- and b-axes. The zinc(II) ion is octahedrally coordinated by
      four carboxylate O atoms from three ligands, a unidentate 4,4'-bipy, and an aqua
      ligand. Each pair of zinc(II) ions is bridged by two carboxylate groups from two
      ligands to form a dimer, and such dimeric units are interconnected by bridging
      ligands to form a double chain. The sulfonate group of the carboxylate sulfonate
      ligand remains noncoordinated and forms a number of hydrogen bonds with aqua
      ligands as well as lattice water molecules.

PMID- 14704086
TI  - Ab initio calculations and normal coordinate analysis of ruthenium tris-alpha
      diimine complexes.
AB  - For the first time, a full scaled quantum chemical normal coordinate analysis has
      been performed on [Ru(LL')(3)](2+) complexes, where LL' = 2,2'-bipyrazine (bpz)
      or 2,2'-bipyrimidine (bpm). Geometric structures were fully optimized using
      density functional theory and an effective core potential basis set. The infrared
      and Raman spectra were calculated using the optimized geometries. The results of
      the calculations provide a highly satisfactory fit to the experimental infrared
      and Raman spectra, and the potential energy distributions allow a detailed
      understanding of the vibrational bands therein.

PMID- 14704087
TI  - Reactivity of the hydrido/nitrosyl radical MHCl(NO)(CO)(P(i)Pr(3))(2), M = Ru,
      Os.
AB  - The reaction of equimolar NO with the 16 electron molecule RuHCl(CO)L(2) (L =
      P(i)Pr(3)) proceeds, via a radical adduct RuHCl(CO)(NO) L(2), onward to form
      RuCl(NO)(CO)L(2) (X-ray structure determination) and RuHCl(HNO)(CO)L(2), in a 1:1
      mole ratio. The HNO ligand, bound by N and trans to hydride, is rapidly degraded
      by excess NO. The osmium complex behaves analogously, but the adduct has a higher
      formation constant, permitting determination of its IR spectrum; both
      MHCl(CO)(NO)L(2) radicals are characterized by EPR spectroscopy, and DFT
      calculations on the Ru system show it to have a "half-bent" Ru-N-O unit with the
      spin density mainly on nitrogen. DFT (PBE) energies rule out certain possible
      mechanistic steps for forming the two products. A survey of the literature leads
      to the hypothesis that NO should generally be considered as a (neutral) Lewis
      base (2-electron donor) when it binds to a 16 electron complex which is resistant
      to oxidation or reduction, and that the resulting N-centered radical has a M-N-O
      angle of approximately 140 degrees, which distinguishes it from NO(-) (bent at
      <140 degrees ) and from NO(+) (>170 degrees ).

PMID- 14704088
TI  - Low melting N-4-functionalized-1-alkyl or polyfluoroalkyl-1,2,4-triazolium salts.
AB  - Butane sulfobetaines 2a,b, zwitterionic oxo perfluorocarboxylates 3a,b, and
      functionalized triazolium bromides 4b,c and 5a-c have been synthesized and
      subsequently reacted to give a series of hydrophilic and hydrophobic fluorinated
      and nonfluorinated N-1-alkyl-N-4-functionalized-triazolium compounds (6a-11b).
      With the exception of 11b (mp 41 degrees C), all are liquids at room temperature.
      Metathesis of the fluorinated quaternary triazolium halides with other anions led
      to the formation of a new class of compounds, namely, [(R)(R(funct))-Taz](+)Y(-),
      Y = PF(6), (CF(3)SO(2))( 2)N, and CF(3)SO(3), in good isolated yields. All of the
      new compounds were characterized by (1)H, (19)F, and (13)C NMR, and MS spectral
      and elemental analyses. Thermal analyses indicate that high temperatures are
      attainable prior to decomposition. DSC studies show glass transitions for several
      samples, and all functionalized compounds, 5-11, have T(g)s or T(m)s <100 degrees
      C. Densities range between 1.4 and 1.61 g cm(-)(3). 1-Heptyl-4-(butyl-4-sulfonic
      acid) triazolium trifluoromethanesulfonate, 6b, in its role as a Bronsted acid,
      is an effective solvent/catalyst for high yield esterification and hetero-Michael
      addition reactions and may be recycled for repetitive use.

PMID- 14704089
TI  - Anionic ligand exchange on ZrPO(4)Cl(dmso): alkoxide and carboxylate derivatives.
AB  - This paper reports the preparation and characterization of a series of organic
      derivatives of ZrPO(4)Cl(CH(3))(2)SO obtained by topotactic anion exchange of
      chloride ligands with several n-alkoxide (RO) and carboxylate groups (RCOO).
      Exchange with alkoxides, with an alkyl chain length from 2 to 8 carbon atoms,
      gave products of general formula ZrPO(4)RO(CH(3))(2)SO. In these derivatives
      alkoxide groups, covalently bonded to zirconium atoms via Zr-O bonds, point
      toward the interlayer region. Carboxylate derivatives, of general formula
      ZrPO(4)[(RCOO)(CH(3))(2)SO](1)(-)(x)(OH H(2)O)(x), were obtained using benzoate
      (x = 0), nitrobenzoate (x = 0.3), and phenylacetate (x = 0.2) groups. The thermal
      behavior of these organic derivatives is discussed. Due to this reactivity,
      ZrPO(4)Cl(CH(3))(2)SO is an attractive precursor for materials chemistry.

PMID- 14704090
TI  - Synthesis and characterization of new Mg(2)Al-paratungstate layered double
      hydroxides.
AB  - Layered double hydroxides (LDHs, or hydrotalcites) with Mg(2+) and Al(3+) cations
      in the mixed metal hydroxide layer and paratungstate anions in the interlayer
      have been prepared. Different methods have been followed: anion exchange with
      Mg,Al LDHs originally containing nitrate or adipate, reconstruction of the LDH
      structure from a mildly calcined Mg(2)Al-CO(3) LDH, and coprecipitation. In all
      cases, the tungsten precursor salt was (NH(4))(10)H(2)W(12)O(42). The prepared
      solids have been characterized by elemental chemical analysis, powder X-ray
      diffraction (PXRD), FT-IR spectroscopy, thermogravimetric (TG) and differential
      thermal (DTA) analyses, scanning electron microscopy (SEM) with EDX (energy
      dispersive X-ray analysis), and nitrogen adsorption at -196 degrees C for surface
      area and surface texture. Most of the synthesis methods used, especially anion
      exchange starting from a Mg(2)Al-NO(3) precursor at low temperature and short
      reaction times, lead to formation of a hydrotalcite with a gallery height of 9.8
      A; increasing the reaction temperature to 70-100 degrees C and maintaining short
      contact times leads to a solid with a gallery height of 7.8 A. Both phases have
      been identified as a result of the intercalation of W(7)O(24)(6)(-) species in
      different orientations in the interlayer space. If the time of synthesis or the
      temperature is increased, a more stable phase, with a gallery height of 5.2 A
      corresponding to a solid with intercalated W(7)O(24)(6)(-), is formed, probably
      with grafting of the interlayer anion on the brucite-like layers. All systems are
      microporous. Calcination at 300 degrees C leads to amorphous species, and
      crystallized MgWO(4) is observed at 700 degrees C.

PMID- 14704091
TI  - Molten flux synthesis of an analogous series of layered alkali samarium
      selenogermanate compounds.
AB  - In this work, we used the molten chalcogenide flux synthetic method to form an
      analogous series of alkali samarium selenogermanates, with the general formula
      ASmGeSe(4) (A = K, Rb, Cs). Using a constant reactant stoichiometry, we relate
      the monoclinic KLaGeSe(4) structure type to the orthorhombic CsSmGeS(4) structure
      type. KSmGeSe(4) [in space group P2(1) with cell parameters a = 6.774(1) A, b =
      6.994(1) A, c = 8.960(2) A, beta = 108.225(3) degrees, and V = 403.2(1) A(3) (Z =
      2)], RbSmGeSe(4) [in space group P2(1)2(1)2(1) with cell parameters a = 6.7347(8)
      A, b = 7.0185(9) A, c = 17.723(2) A, and V = 837.7(2) A(3) (Z = 4)], and
      CsSmGeSe(4) [in space group P2(1)2(1)2(1) with cell parameters a = 6.707(2) A, b
      = 7.067(2) A, c = 18.334(6) A, and V = 869.1(5) A(3) (Z = 4)] were formed under
      identical synthetic conditions by changing the identity of the alkali ion from K
      to Rb or Cs, respectively. Additionally, with the substitution of sodium into the
      reaction, a triclinic structure with the approximate formula NaSmGeSe(4) was
      found with the cell parameters a = 6.897(2) A, b = 9.919(2) A, c = 11.183(2) A,
      alpha = 84.067(4) degrees, beta = 88.105(4) degrees, gamma = 73.999(4) degrees,
      and V = 731.5(3) A(3). In addition to single-crystal diffraction, Raman and
      diffuse reflectance UV-visible spectroscopic measurements have been used to
      characterize these compounds.

PMID- 14704093
TI  - SAGE is far more sensitive than EST for detecting low-abundance transcripts.
AB  - BACKGROUND: Isolation of low-abundance transcripts expressed in a genome remains
      a serious challenge in transcriptome studies. The sensitivity of the methods used
      for analysis has a direct impact on the efficiency of the detection. We compared
      the EST method and the SAGE method to determine which one is more sensitive and
      to what extent the sensitivity is great for the detection of low-abundance
      transcripts. RESULTS: Using the same low-abundance transcripts detected by both
      methods as the targeted sequences, we observed that the SAGE method is 26 times
      more sensitive than the EST method for the detection of low-abundance
      transcripts. CONCLUSIONS: The SAGE method is more efficient than the EST method
      in detecting the low-abundance transcripts.

PMID- 14704094
TI  - Identifying chironomids (Diptera: Chironomidae) for biological monitoring with
      PCR-RFLP.
AB  - Chironomids are excellent biological indicators for the health of aquatic
      ecosystems, but their use at finer taxonomic levels is hindered by morphological
      similarity of species at each life stage. Molecular markers have the potential to
      overcome these problems by facilitating species identification particularly in
      large-scale surveys. In this study, the potential of the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) approach was tested
      to rapidly distinguish among chironomids within a geographic area, by considering
      chironomid species from Melbourne, Australia. By comparing molecular markers with
      diagnostic morphological traits, RFLP profiles of the cytochrome oxidase I (COI)
      region were identified that were specific to genera and some common species.
      These profiles were used to develop an RFLP-based key, which was validated by
      testing the markers on samples from several wetlands and streams. As well as
      allowing for rapid identification of species that are difficult to separate on
      morphological grounds, this approach also has the potential to resolve current
      taxonomic ambiguities.

PMID- 14704095
TI  - Efficacy of mosquito nets treated with insecticide mixtures or mosaics against
      insecticide resistant Anopheles gambiae and Culex quinquefasciatus (Diptera:
      Culicidae) in Cote d'Ivoire.
AB  - Only pyrethroid insecticides have so far been recommended for the treatment of
      mosquito nets for malaria control. Increasing resistance of malaria vectors to
      pyrethroids threatens to reduce the potency of this important method of vector
      control. Among the strategies proposed for resistance management is to use a
      pyrethroid and a non-pyrethroid insecticide in combination on the same mosquito
      net, either separately or as a mixture. Mixtures are particularly promising if
      there is potentiation between the two insecticides as this would make it possible
      to lower the dosage of each, as has been demonstrated under laboratory conditions
      for a mixture of bifenthrin (pyrethroid) and carbosulfan (carbamate). The effect
      of these types of treatment were compared in experimental huts on wild
      populations of Anopheles gambiae Giles and the nuisance mosquito Culex
      quinquefasciatus Say, both of which are multi-resistant. Four treatments were
      evaluated in experimental huts over six months: the recommended dosage of 50 mg
      m(-2) bifenthrin, 300 mg m(-2) carbosulfan, a mosaic of 300 mg m(-2) carbosulfan
      on the ceiling and 50 mg m(-2) bifenthrin on the sides, and a mixture of 6.25 mg
      m(-2) carbosulfan and 25 mg m(-2) bifenthrin. The mixture and mosaic treatments
      did not differ significantly in effectiveness from carbosulfan and bifenthrin
      alone against anophelines in terms of deterrency, induced exophily, blood feeding
      inhibition and overall mortality, but were more effective than in earlier tests
      with deltamethrin. These results are considered encouraging, as the combination
      of different classes of insecticides might be a potential tool for resistance
      management. The mixture might have an advantage in terms of lower cost and
      toxicity.

PMID- 14704096
TI  - Intraguild predation among ladybeetles and a green lacewing: do the larval spines
      of Curinus coeruleus(Coleoptera: Coccinellidae) serve a defensive function?
AB  - Laboratory experiments examined interspecific interactions between larvae of
      three coccinellid species, Curinus coeruleus Mulsant (Chilocorinae), Harmonia
      axyridis Pallas and Olla v-nigrum (Mulsant) (Coccinellinae), and between these
      and larvae of the green lacewing, Chrysoperla rufilabris (Burmeister). Larvae of
      C. coeruleus, although defended on their dorsal surface with long spines, had the
      smallest mandibles, were the slowest-moving, and the least successful in
      interspecific larval combat. The long spines of third instar C. coeruleusappeared
      to reduce their palatability as food to H. axyridis and O. v-nigrum larvae in
      choice tests with dead larvae, but were not an effective defence against these
      species in Petri dish arenas. Larvae of O. v-nigrum had a smooth dorsal surface,
      were intermediate in terms of mandible size, but were the fastest moving, a trait
      that benefited their survival in intraguild combat. Larvae of H. axyridis were
      intermediate with respect to dorsal spines and speed of movement, but had the
      largest mandibles. This species was the most effective intraguild combatant among
      the coccinellids and the only one to successfully compete against C. rufilabris
      larvae of similar age. The speed, manoeuverability and long mandibles of C.
      rufilabris enabled them to impale coccinellid larvae at a relatively safe
      distance. The spines of C. coeruleus larvae impeded laterally oriented attacks by
      C. rufilabris, but did not provide sustained protection from repeated attacks.
      Success in these interactions appeared largely a function of offensive weaponry
      (mandible size and morphology) and speed of movement, although the role of dorsal
      spines as defensive structures was not ruled out. Rates of larval cannibalism
      were highest for C. rufilabris and largely mirrored the level of aggression
      observed in interspecific combat for each species.

PMID- 14704097
TI  - Discrimination of the closely related biocontrol agents Macrolophus melanotoma
      (Hemiptera: Miridae) and M. pygmaeus using mitochondrial DNA analysis.
AB  - The separation of the closely related predatory species Macrolophus melanotoma
      Costa (= M. caliginosus Wagner) and Macrolophus pygmaeus (Rambur) based
      exclusively on the different colour pattern of the first antennal segment (white
      central band in M. melanotoma and entirely black in M. pygmaeus) is rather
      precarious and their taxonomic status is still in doubt. In the present study
      their taxonomic status was evaluated by DNA confirmatory analysis and
      hybridization experiments between M. pygmaeus and a Macrolophus taxon, resembling
      M. melanotoma, with a first antennal segment entirely black or with a white
      central band collected from Dittrichia viscosa (L.) W. Greuter (Asteraceae) in
      southern Greece. Adult females from Dittrichia plants hybridized with males of M.
      pygmaeus and vice versa did not produce viable eggs. The Macrolophus species from
      Dittrichia irrespective of the first antennal segment coloration differed from M.
      pygmaeusin digestive patterns generated by AseI, XbaI, and MseI on 16S rRNA and
      in RAPD profiles produced by the primers OPA-18 and OPA-20. These results
      demonstrate that on Dittrichia plants there is a distinct dimorphic taxon, M.
      melanotoma, as it is the only species of the genus Macrolophus bearing a first
      antennal segment with a central white band. Given the limitation of the
      coloration pattern, the mtDNA genetic markers are the appropriate method for the
      identification of M. melanotomaand M. pygmaeus.

PMID- 14704098
TI  - A morphological study of the Anopheles punctulatus group (Diptera: Culicidae) in
      the Solomon Islands, with a description of Anopheles (Cellia) irenicus Schmidt,
      sp.n.
AB  - A description of Anopheles (Cellia) irenicus Schmidt, sp.n. (formerly A. farauti
      No. 7) is provided. This species is one of six recorded from the Solomon Islands
      within the A. punctulatus group, which contains the major vectors of the
      causative agents of malaria and lymphatic filariasis in the southwest Pacific.
      Morphological markers are described for adult females, fourth-instar larvae and
      pupae that identify most specimens of A. irenicus. Keys are presented to
      distinguish members of the A. punctulatus group in the Solomon Islands.

PMID- 14704099
TI  - The Anopheles maculipennis complex (Diptera: Culicidae) in Iran: molecular
      characterization and recognition of a new species.
AB  - Mosquitoes of the Anopheles maculipennis complex were collected in nine provinces
      of Iran (Esfahan, Fars, Gilan, Golestan, Kohkiluyeh va Boyerahmad, Mazandaran,
      Tehran, Azarbaijan-e Gharbi and Zanjan) between June 1983 and September 2002. The
      nuclear rDNA ITS2 sequences of 86 specimens were compared with those of seven
      species of the complex available in GenBank. Three genetically distinct species
      of the complex were distinguished: A. maculipennis Meigen, A. sacharovi Favre and
      a previously unrecognized species. The last species is most similar to, but
      clearly distinct from, A. martinius Shingarev and A. sacharovi. The taxonomy of
      A. martinius and A. sacharovi is critically reviewed, and justification is
      provided for formally recognizing the third species as Anopheles persiensis sp.n.
      The new species is the first culicid to be characterized and named principally on
      the basis of DNA evidence. Anopheles persiensis was collected only in the
      northern Caspian Sea littoral provinces of Gilan and Mazandaran, and it seems
      likely that this species could be responsible for malaria transmission in this
      region that was previously attributed to A. maculipennis. A species-specific RFLP
      PCR assay based on ITS2 sequences was developed to facilitate further studies of
      the three species in Iran.

PMID- 14704100
TI  - Changes in genotypic composition of Myzus persicae (Hemiptera: Aphididae) on
      tobacco during the past two decades in Japan.
AB  - Ninety-nine and 476 clones of Myzus persicae (Sulzer) were sampled on tobacco at
      Kyoto (Shimogamo) (1996-2000) and at 23 other localities (1998-1999) in Japan,
      respectively. The clones were classified into colour-esterase forms,
      distinguished by combinations of body colour and electrophoretically detectable
      esterases, to verify the changes in genotypic composition during the past two
      decades. Fifteen and 31 colour-esterase forms were found at Kyoto (Shimogamo) and
      at 23 other localities, respectively. Fourteen (representing c. 95% of the total
      clones sampled) and 24 (c. 44%) colour-esterase forms, respectively, were
      different from those found on tobacco during 1978-1985. The frequency of the
      green form and the very highly insecticide-resistant form increased. More than
      half of the colour-esterase forms found in the present survey were newly
      detected. The factors associated with these changes are discussed.

PMID- 14704101
TI  - Confirmation by DNA analysis that Contarinia maculipennis (Diptera:
      Cecidomyiidae) is a polyphagous pest of orchids and other unrelated cultivated
      plants.
AB  - The cytochrome oxidase subunit I gene in mitochondrial DNA of 53 larvae of
      Contarinia maculipennis Felt from flower buds of various host plants, collected
      from Hawaii, Japan and Thailand was analysed. Monophyly of the clade including C.
      maculipennis from Hawaii, Thailand and Japan was supported. There was no
      sequential variation within the specimens from Hawaii and Japan, which differed
      from one another by 6 bp (1.37%). Three haplotypes were recognized in specimens
      from Thailand but differences from Hawaiian and Japanese specimens were small.
      Overall, there were no differences in the 146 deduced amino acid residues. It is
      therefore concluded that C. maculipennis is a polyphagous species that can
      develop on plant hosts representing at least seven botanical families. This pest
      of Dendrobium flower buds in glasshouses is considered to have entered Hawaii,
      Florida and Japan from Southeast Asia, and was recently intercepted in the
      Netherlands. Infestations have established and spread in orchid glasshouses,
      causing concern about the possibility of more extensive damage to orchids and to
      crops, such as bitter gourd, grown in close proximity to orchid glasshouses in
      Japan. The potential usefulness of DNA analysis in determining host plant ranges
      of morphologically identical cecidomyiid species that are currently identified
      solely on differences of host plant is emphasized.

PMID- 14704102
TI  - Food-plant effects on larval performance do not translate into differences in
      fitness between populations of Panolis flammea (Lepidoptera: Noctuidae).
AB  - In the UK, Panolis flammea (Denis & Schiffermuller) is a pest of monocultures of
      non-native lodgepole pine Pinus contorta Douglas, but not of the indigenous host
      Scots pine P. sylvestrisL. This difference in population dynamics may be due to
      the adaptation of P. flammea populations to the phenology, chemical composition
      and natural enemy complement of lodgepole pine. To ascertain if there was local
      adaptation of P. flammea populations to lodgepole pine, this study tested for
      improved performance of both larvae and adults on the host plant species from
      which they were sourced, compared with their performance on the alternative host
      plant species. No difference was found in the relative mean performance of
      populations sourced from Scots pine or lodgepole pine plantations, when fed on
      Scots or lodgepole pine foliage. Larvae grew faster on Scots pine but this
      difference did not translate into differences in pupal weight, female body weight
      or fecundity. Indeed, those insects that had fed on lodgepole pine had a longer
      lifespan than those that had fed on Scots pine, which, if translated into greater
      probability of mating or higher fecundity, could contribute to the observed
      outbreak dynamics in the field. The prediction that the observed outbreak
      dynamics of P. flammea can be explained by the existence of populations locally
      adapted to lodgepole pine was not supported. These results cast doubt on the use
      of larval growth parameters as surrogates of fitness in Lepidoptera.

PMID- 14704103
TI  - Distribution, host range, and climatic constraints on Centistes gasseni
      (Hymenoptera: Braconidae), a South American parasitoid of cucumber beetles,
      Diabrotica spp. (Coleoptera: Chrysomelidae).
AB  - The genus Diabrotica includes a large number of pest species, including some of
      the most important crop pests of the Americas. The parasitoid Centistes gasseni
      Shaw is the first braconid to be described parasitizing Diabrotica in South
      America, and high natural infestations are reported. Field and experimental
      observations on the host range, distribution and biology of this parasitoid are
      described. Centistes gasseniwas collected in southern Brazil, eastern Paraguay
      and northeastern Argentina, in a region comprising humid lowlands and highlands,
      and cool temperate to warm subtropical climates, with regular rainfall in excess
      of 1300 mm. Three Diabroticaspecies, D. limitata (Sahlberg), D. speciosa (Germar)
      and D. viridula (Fabricius) were found to host the parasitoid, with mean percent
      parasitism of 5.4, 2.0 and 1.0%, respectively. Diabrotica speciosa and D.
      viridula are the two most important pest Diabroticaspecies in South America.
      Laboratory experiments with field-collected beetles and parasitoid cocoons
      indicated that C. gasseni overwinters in adult host beetles, remaining dormant in
      its live host below developmental temperatures. A potential distribution of C.
      gasseni in North America is proposed based on its known climatic range and the
      distribution of the main pest species of adult overwintering North American
      Diabrotica.

PMID- 14704104
TI  - Basic biology and small-scale rearing of Celatoria compressa(Diptera:
      Tachinidae), a parasitoid of Diabrotica virgifera virgifera (Coleoptera:
      Chrysomelidae).
AB  - The tachinid Celatoria compressa Wulp has been evaluated as a candidate
      biological control agent for the western corn rootworm, Diabrotica virgifera
      virgiferaLeConte, in Europe, where it is an invasive alien pest of maize. Special
      emphasis has been placed on understanding aspects of the parasitoid basic biology
      and on developing a rearing technique for a small-scale production of C.
      compressapuparia. The age of C. compressa adults was found to be the most crucial
      factor in achieving mating. Only newly emerged, 1-h-old females, mated
      successfully with 2- to 5-day-old males, achieving a success rate of 74%. After
      mating, a prelarviposition period of 4 days occurred. The 5-day-old C. compressa
      females inserted their eggs containing fully-developed first instars directly
      into adults of D. v. virgifera. Total larval and pupal developmental time,
      including a pre-larviposition period of 4 days, was 29 days under quarantine
      laboratory conditions (25 degrees C daytime, 15 degrees C at night, L:D 14:10,
      50% +/- 10% r.h). Females of C. compressa were capable of producing on average 30
      puparia throughout a female's mean larviposition period of 15 days. A large
      number of host attacks by C. compressa were unsuccessful, resulting in a mean
      larviposition success rate of 24% per female. Parasitoid females appear to have
      difficulties inserting the egg through the intersegmental sutures or membranes
      around leg openings of the host adults. Although the small-scale rearing
      technique of C. compressa presented is both time and labour intensive, C.
      compressa has been reared successfully for at least 20 successive generations
      without shifting the 1 male : 1 female sex ratio using a non-diapause strain of
      D. v. virgifera.

PMID- 14704105
TI  - Reassessing PSA.

PMID- 14704106
TI  - Point: It's never too soon.
AB  - A multidisciplinary approach to prostate cancer has become the rule and not the
      exception. Involving the entire team, which includes a medical oncologist, from
      the time of initial diagnosis is optimal. This facilitates maximal patient
      education regarding treatment options and enhances informed decision making. A
      coordinated approach also promotes enrollment on clinical trials, which are
      often, multimodality, especially in high-risk early stage prostate cancer.
      Integrated therapeutic strategies throughout the patient's disease course can
      improve both patient care and satisfaction

PMID- 14704107
TI  - Counterpoint: Men should be treated for hormone refractory prostate cancer with
      systemic chemotherapy when they are symptomatic, and not before.
AB  - The benefits of chemotherapy in men with symptomatic HRPC include pain relief,
      better physical functioning and improved quality of life. These have been well
      established in randomized trials. A meaningful or statistically significant
      improvement in survival has yet to be demonstrated. In the absence of a survival
      benefit, there is concern that treating men when they are free of symptoms may
      have a negative impact upon quality of life due to drug related toxicity. It will
      also limit or eliminate any therapeutic options when symptoms eventually develop
      and therapy is needed most.

PMID- 14704108
TI  - Prostate specific antigen: an updated review.
AB  - Since its discovery in 1979, serum PSA has revolutionized how physicians manage
      men with prostate cancer. PSA screening, although currently under much debate,
      has been recommended by most North American medical bodies, including the
      Canadian Urological Association, to be performed as a shared-decision making
      process after discussing with patients the pros and cons of treatment. Although
      most commonly thought of as a screening tool, serum PSA has also been used to
      predict tumor volume, stage and prognosis in patients before and after treatment.
      In this review, we examine PSA testing and its effectiveness in the diagnosis and
      management of prostate cancer. Further, we also evaluate recent literature
      regarding the use of PSA derivatives and other prostate cancer markers, such as
      proPSA, bPSA, and hk2

PMID- 14704109
TI  - Safety and efficacy of extracorporeal shock wave lithotripsy in infants.
AB  - PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) in older children appears
      to have comparable results when compared to adults, no study has focused on its
      use in younger children. We reviewed our ESWL experience in children under age
      3.5 years to evaluate its safety, and define optimal treatment parameters.
      METHODS: We retrospectively reviewed consecutive medical and diagnostic imaging
      records from three ESWL centers, pertaining to 34 children under 3.5 years of age
      (36 renal units-RU). The children were from two distinct populations served
      exclusively by the three centers. We analyzed patient presentation, etiology,
      age, weight, stone size, preoperative interventions, energy settings, number of
      shock waves, number of treatments, success (stone fragments < 2 mm), and
      complications. We performed all forty-nine procedures under general anesthesia
      and modified the Dornier MFL 5000 table and the Dornier HM3 gantry to improve
      coupling and localizing of the calculi. RESULTS: In each population, we noted
      similar presentations, etiologies, and treatment parameters. Patient age ranged
      from 6 to 40 months (mean 23.4 months). Stone size ranged from 4 mm to 22 mm
      diameter (average 13 mm). ESWL parameters included an average of 2210 shocks
      (range 900-3400) at average of 20.9 kV (range 19 kV-25 kV). Preoperative ureteral
      stent placement was not shown to be beneficial. Our one and multiple treatment
      ESWL success rates were 66% and 86%, respectively. No major acute or long-term
      complications occurred. CONCLUSIONS: We successfully performed ESWL using
      treatment parameters similar to adults in 86% of children under 3.5 years without
      major complications. Modifications of the positioning device improved coupling
      and localization in smaller patients. Routine preoperative ureteral stenting for
      large stones is not recommended.

PMID- 14704110
TI  - Radiotherapy for muscle-invasive urinary bladder cancer in elderly patients.
AB  - OBJECTIVE: To review retrospectively the outcome and toxicity of Radiotherapy
      (RT) in the cohort of elderly patients (EP) with muscle-invasive urinary bladder
      carcinoma (MIUBC). METHODS: Thirty-six EP were treated with RT with radical
      intent. The age of the cohort ranged from 71 to 89 years with a median of 79
      years. Eighty percent of the patients had Easter Cooperative Oncology Group
      (ECOG) 0 and 1 performance status. Conventional and accelerated fractionation RT
      regimen were utilized. RESULTS: With median follow up of 45.8 months, the median
      survival was 23.9 months. There was a trend toward better survival in patients
      treated with the accelerated fractionation regimen. The median survival for that
      group (12) has not yet been reached, where it is 9.7 months for the group (24)
      treated with conventional fractionation. Treatment related toxicity was low for
      any RT regimens. CONCLUSION: RT is well tolerated by EP with good baseline
      performance status. The role of accelerated fractionation should be tested by
      conducting randomized trials.

PMID- 14704111
TI  - Upper tract imaging after ureteroscopic holmium:YAG laser lithotripsy: when is it
      necessary?
AB  - INTRODUCTION/OBJECTIVE: Advances in ureteroscope design and refinements of
      ancillary instrumentation have resulted in an expanded role for ureteroscopy in
      the management of urinary calculi. Technological enhancements coupled with
      improved endourologic skills have also been associated with a reduction in
      procedural-related complications. Historically, postoperative imaging with
      ultrasound (U/S) or intravenous pyelogram (IVP) had been advocated to rule out
      persistent obstruction due to retained stone fragments or ureteral stricture. The
      purposes of this study were to evaluate the incidence of postoperative ureteral
      obstruction in a contemporary series of patients undergoing ureteroscopic
      holmium:YAG laser lithotripsy without basket extraction of fragments and to
      identify patient, stone and operative factors predictive of which patients will
      benefit from postoperative imaging. MATERIALS AND METHODS: The charts and imaging
      studies of 89 consecutive patients undergoing a total of 94 holmium:YAG
      ureteroscopic lithotripsy procedures between December 1998 and December 2000 were
      retrospectively reviewed. Preoperative, intraoperative and postoperative data
      were collected and analyzed. The primary outcome measure was the incidence of
      postoperative ureteral obstruction documented on upper tract imaging. Secondary
      outcome measures included interventions required for postoperative obstruction
      and other nonobstructive postoperative complications. RESULTS: Twenty-eight
      females and 61 males were studied, with a mean patient age of 54 (range 13-80)
      years. Fifty-five percent of patients underwent related procedures prior to
      referral to our tertiary endourology centre. Complete clinical and radiological
      follow-up is available for 68 of 89 (76.4%) patients, with a mean follow-up
      duration of 24.2 weeks. Overall stone-free rate was 97%. Six patients had
      evidence of urinary tract obstruction on follow-up radiological assessment, two
      from residual stone fragments and four from ureteral stricture. Each of these
      four patients had at least one preoperative risk factor for ureteral stricture.
      CONCLUSIONS: Routine postoperative upper tract imaging is not necessary in all
      patients undergoing uncomplicated ureteroscopic holmium:YAG laser lithotripsy.
      Indications for upper tract imaging include chronic stone impaction, significant
      ureteral trauma, pre-existing renal function impairment, endoscopic evidence of
      stricture and postoperative flank pain or fever.

PMID- 14704112
TI  - Urethral erosion following autologous rectus fascial pubovaginal sling.
AB  - Urethral erosion following pubovaginal sling is a rare occurrence. When synthetic
      sling materials are used urethral erosion often necessitates removal of the sling
      and urethral reconstruction. The literature is sparse with respect to the best
      approach to fascial sling erosion. We report a case of a 73 year-old woman who
      underwent a pubovaginal sling using autologous rectus fascia for treatment of
      stress urinary incontinence (SUI). She developed urethral erosion following 2
      weeks of clean intermittent catheterization (CIC). Visual internal urethrotomy
      (VIU) was performed to incise the sling and the prolene sutures were removed to
      eliminate any tension. The patient subsequently voided spontaneously and had
      resolution of her SUI. This case demonstrates that urethral erosion may occur
      even when fascial slings are used. Unlike synthetic slings, when autologous
      fascia is used, the tissue may be left in-situ. A minimally invasive approach may
      achieve an excellent result without the need for complex surgical repair.

PMID- 14704113
TI  - Feasibility of microsurgical reconstruction of the male reproductive tract after
      percutaneous epididymal sperm aspiration (PESA).
AB  - For obstructive azoospermia, surgical sperm retrieval from the epididymis for
      IVF/ICSI is an established management. However, various recent studies have
      established that surgical reconstruction with vasovasostomy or vasoepididymostomy
      remains a more cost-effective treatment option than upfront assisted
      reproduction. After epididymal sperm retrieval, fibrosis and scarring of the
      punctured epididymal tubule can lead to complete epididymal obstruction. The
      feasibility of surgical reconstruction after surgical epididymal sperm retrieval
      has not been established. We describe two cases of bilateral microsurgical
      vasoepididymostomy, using a new 2-suture longitudinal intussusception technique
      we previously described, after previous successful bilateral percutaneous
      epididymal sperm aspiration (PESA). In both cases, motile sperm were found in
      ejaculate in the first post-operative semen analysis at 6 weeks and 2 months. We
      conclude that even in men with previous epididymal sperm retrieval, surgical
      reconstruction remains a feasible management option for fertility.

PMID- 14704114
TI  - Metastatic Leydig cell tumor of the testicle in a young African American male.
AB  - Malignant Leydig cell tumor (LCT) of the testis are extremely rare and account
      for less than 0.2% of all testicular cancers. Testicular tumors of all
      histological types rarely occur in African American men. The authors describe a
      rare case of an advanced stage malignant LCT arising from the testicle of an
      African American man at the young age of 35, who presented with hemoptysis and a
      productive cough. Clinical features and treatment of Leydig cell tumor of the
      testis are discussed.

PMID- 14704115
TI  - Advances in modeling of biomolecular interactions.
AB  - Modeling of molecular interactions is increasingly used in life science research
      and biotechnology development. Examples are computer aided drug design,
      prediction of protein interactions with other molecules, and simulation of
      networks of biomolecules in a particular process in human body. This article
      reviews recent progress in the related fields and provides a brief overview on
      the methods used in molecular modeling of biological systems.

PMID- 14704116
TI  - Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on
      antinociception of propofol.
AB  - AIM: To study the effects of intrathecal (it) agonists and antagonists of N
      methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptors and NMDAR1 antisense oligodeoxynucleotides (AS
      ODN) on the antinociception of propofol. METHODS: Hot-plate test (HPPT) and
      acetic acid-induced writhing test were used to measure the nociceptive thresholds
      in mice. The effects of intrathecal NMDA, AMPA, MK-801, NBQX, or NMDAR1 AS ODN on
      the antinociception of propofol were observed. RESULTS: Propofol (25, 50 mg/kg,
      ip) displayed an appreciable antinociceptive effect in hot-plate test and acetic
      acid-induced writhing test. NMDA (12.5, 25 ng, it) or AMPA (1.25, 2.5 ng, it)
      exhibited no effects on the behavior but decreased HPPT significantly compared
      with basal HPPT and aCSF group (P<0.05, P<0.01). No effects on behavior and HPPT
      were obtained in NMDA (6.25 ng, it) or AMPA (0.625 ng, it) groups. NMDA (6.25,
      12.5, and 25 ng, it) dose-dependently decreased the HPPT in propofol-treated
      group. AMPA (1.25, 2.5 ng, it) also decreased HPPT significantly. MK-801 (0.25,
      0.5 microg, it) or NBQX (0.25, 0.5 microg, it) groups had no behavioral changes,
      two antagonists 0.5 microg but not 0.25 microg increased HPPT in conscious or
      propofol-treated mice. AS ODN (5, 10, and 20 microg, it) groups exhibited dose
      dependent increased in HPPT in propofol-treated groups compared with aCSF group
      (P<0.05, P<0.01). CONCLUSION: Both agonists NMDA and AMPA reversed the
      antinociception of propofol. MK-801, NBQX, and NMDAR1 AS ODN potentiated the
      antinociceptive effects of propofol. Propofol produced antinociception through an
      interaction with spinal NMDA and AMPA receptors in mice.

PMID- 14704117
TI  - Therapeutic efficacy of charcoal hemoperfusion in patients with acute severe
      dichlorvos poisoning.
AB  - AIM: To assess the efficacy of hemoperfusion (HP) in the treatment of the
      patients with acute severe dichlorvos (DDVP) poisoning. METHODS: One hundred and
      eight patients with acute severe DDVP poisoning in the two teaching hospitals
      were enrolled. Sixty-seven patients were treated with HP (HP group) and forty-one
      patients accepted traditional treatment only as the control. Serum concentration
      of DDVP was determined by gas chromatography. RESULTS: The duration of coma,
      impaired consciousness, ICU stay, and mechanical ventilation was significantly
      shorter in the HP group than that in the control. The cumulative dosages (mg) of
      atropine required either in the first 24 h on admission (442+/-436 vs 899+/-485
      in the control, P<0.01) or within the hospital (568+/-574 vs 1228+/-982 in the
      control, P<0.01) were markedly reduced in the HP patients. The lower incidence of
      mechanical ventilation required (13.4 % vs 36.6 % P<0.01), respiratory muscular
      paralysis (4.5 % vs 17.1 %, P<0.05) and the lower mortality of death (7.5 % vs
      34.1 %, P<0.01) were observed in the HP group. HP could accelerate the recovery
      of suppressed cholinesterase activity. After the procedure, the DDVP level was
      decreased from (11+/-4) to (7+/-3) mg/L in parallel with a decline in APACHE II
      Score or dopamine dose and a rise in Glasgow Coma Scale (P<0.05). In addition,
      the mean values of peak clearance and reduction rate were (87+/-17) mL/min and 44
      %+/-11 %, respectively. CONCLUSION: The rapid fall in blood DDVP level and the
      dramatic clinical response suggest that HP is effective in the treatment of acute
      severe DDVP poisoning.

PMID- 14704118
TI  - Activation of mitochondrial ATP-sensitive potassium channels delays ischemia
      induced cellular uncoupling in rat heart.
AB  - AIM: To test the hypothesis that cellular uncoupling induced by myocardial
      ischemia is mediated by activation of mitochondrial ATP-sensitive potassium
      channels (mitoKATP). METHODS: Rat hearts were perfused on a Langendorff apparatus
      and subjected to 40-min ischemia followed by 30-min reperfusion (I/R). Changes in
      cellular coupling were monitored by measuring whole-tissue resistance. RESULTS:
      (1) In hearts subjected to I/R, the onset of uncoupling started at (13.3+/-1.0)
      min of ischemia; (2) Ischemic preconditioning (IPC) delayed the onset of
      uncoupling until (22.7+/-1.3) min. Blocking mitoKATP channels with 5
      hydroxydecanoate (5-HD) before the IPC abolished the uncoupling delay [(12.6+/
      1.6) min]; (3) Calcium preconditioning (CPC) had the same effect as IPC. And this
      effect was reversed by blocking the mitoKATP channel again. In the CPC group the
      onset of uncoupling occurred after (20.6+/-1.3) min, and this was canceled by 5
      HD [(13.6+/-0.8) min]; (4) In hearts pretreated with the specific mitoKATP
      channel opener diazoxide before sustained ischemia, the onset was delayed to
      (18.4+/-1.4) min; (5) 5-HD canceled the protective effects of diazoxide (12.6+/
      1.0) min; and both the L-type Ca2+ channel inhibitor verapamil and the free
      radical scavenger N-(2-mercaptopropionyl)glycine, reduced the extended onset time
      induced by diazoxide [to (13.3+/-1.8) min and (13.4+/-2.1) min, respectively].
      CONCLUSION: IPC and CPC delay the onset of cellular uncoupling induced by acute
      ischemia in rat heart, and the underlying mechanism involves activation of the
      mitoKATP channels.

PMID- 14704119
TI  - beta-Adrenoceptors potentiate alpha1-adrenoceptor-mediated inotropic response in
      rat left atria.
AB  - AIM: To investigate whether stimulation of beta-adrenoceptor (AR) and its
      subtypes augment alpha1-AR-evoked positive inotropic response and inositol
      phosphate (InsP) accumulation in isolated rat left atria. METHODS: Inotropic
      response was determined by contractile function experiment in isolated
      electrically driven rat left atria. 3H-InsP accumulations were measured by 3H
      inositol incorporation and column chromatography. RESULTS: (1) Stimulation of
      alpha1-AR by phenylephrine (PE) or norepinephrine (NE) in the presence of
      propranolol (Prop) evoked positive inotropic response and 3H-InsP accumulations,
      while stimulation of beta-AR by isoprenaline (ISO) or NE in the presence of
      phentolamine (Phen) only evoked positive inotropic response, but not 3H-InsP
      accumulations. (2) Simultaneous stimulation of alpha1- and beta-AR by NE or ISO
      plus PE significantly shifted the concentration-dependent inotropic response
      curves and 3H-InsP accumulation curves to the left and upward compared with
      individual alpha1-AR stimulation by PE or NE in the presence of Prop. (3) In the
      presence of ICI118551 (selective beta2-AR antagonist) or CGP12177 (selective
      beta1-AR antagonist), stimulation of either beta1- or beta2-AR did not change
      alpha1-AR-evoked inotropic response and 3H-InsP accumulations. CONCLUSION:
      Stimulation of beta1-AR and beta2-AR potentiates alpha1-AR-mediated positive
      inotropic response and InsP accumulation in isolated rat left atria.

PMID- 14704120
TI  - Effects of dl-praeruptorin A on nucleus factor-kappaB and tumor necrosis factor
      alpha expression in ischemia-reperfusion hearts.
AB  - AIM: To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB
      (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression
      in ischemia-reperfusion (I/R) myocardium. METHODS: Langendorff's isolated rat
      heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF
      kappaB activity in nucleus was analyzed by Sandwich Enzyme-Linked Immunosorbent
      Assay (ELISA). TNF-alpha level in cytoplasm was measured by radioimmunoassay.
      Infiltration of neutrophils was observed using Hematoxylin-Eosin staining under
      optical microscope. RESULTS: Pd-Ia 1.0 micromol/L with 30-min preventive
      perfusion decreased NF-kappaB activity from 0.98+/-0.13 to 0.65+/-0.17 (P<0.05 vs
      solvent) and down-regulated TNF-alpha expression from 13.7+/-6.1 microg/L to
      9.4+/-2.7 microg/L (P<0.01 vs solvent) under conditions with increase of coronary
      flow, negative inotropic action, inhibition of creatine kinase and without
      chronotropic action, whereas, infiltration of neutrophils was mild. CONCLUSION:
      Pd-Ia inhibited NF-kappaB activativity in I/R myocardium and led to down
      regulation of TNF-alpha expression, which might be one of molecular mechanisms of
      Pd-Ia in cardioprotection.

PMID- 14704121
TI  - Inhibitory effect of antisense oligodeoxynucleotide to p44/p42 MAPK on
      angiotensin II-induced hypertrophic response in cultured neonatal rat cardiac
      myocyte.
AB  - AIM: To explore the inhibitory effect of antisense oligonucleotide (ODN) to
      mitogen activated protein kinase(MAPK) on cardiomyocyte hypertrophy induced by
      angiotensin II (Ang II). METHODS: A 17-mer phosphorothioate-protected antisense
      ODN directed against the initiation of translation sites of the p42 and p44 MAPK
      isoforms by liposomal transfection was applied to inhibit the translation of
      p44/p42 MAPK mRNA. The sense and random ODNs to p44/p42MAPK were used as sequence
      controls. Neonatal cardiac myocytes were exposed to Ang II (10 nmol/L) for 5 min
      and then harvested in lysis buffer for the measurement of the activity and the
      phosphorylated protein content of p44/p42MAPK that were tested by P-81
      phosphocellulose filter paper method and Western blotting, respectively. The rate
      of protein synthesis by [3H]leucine incorporation and the diameter of cell were
      measured after exposure to Ang II for 24 h and 72 h, respectively. RESULTS: In
      cardiac myocyte Ang II increased p44/p42 MAPK activity and phosphorylated protein
      content by 140 % and 699 %, and also increased [3H]leucine incorporation and cell
      diameter by 40 % and 27 %. c-fos and c-myc mRNAs were induced significantly after
      exposure to Ang II. Antisense ODN to p44/p42MAPK (0.2 micromol/L) reduced Ang II
      induced MAPK activity by 30 %, and phophorylated MAPK protein expression by 59 %
      in cardiac myocyte, and inhibited c-fos and c-myc mRNA expression induced by Ang
      II by 44 % and 43 %, respectively. The diameter and the rate of protein synthesis
      of cardiac myocyte induced by Ang II were decreased by 16 % and 22 % after
      pretreatment with antisense ODN to p44/p42MAPK. CONCLUSION: Antisense ODN to
      p44/p42 MAPK inhibited the increase of rate of protein synthesis, and the
      augmentation of cell diameter and expression of c-fos and c-myc mRNA induced by
      Ang II in cultured cardiac myocytes. p44/p42 MAPK played a critical role in the
      hypertrophic response induced by Ang II in cultured neonatal rat cardiac
      myocytes.

PMID- 14704122
TI  - Effects of 15-deoxy-delta12,14-prostaglandin J2 on cell proliferation and
      apoptosis in ECV304 endothelial cells.
AB  - AIM: To investigate the effects of 15-deoxy-delta12,14-prostaglandin J2 (15d
      PGJ2) on cell proliferation and apoptosis in ECV304 endothelial cells and related
      molecular mechanism. METHODS: MTT, Hoechst33258, TUNEL, Flow cytometry, DNA
      ladder, RT-PCR, Western blot, and electrophoretic mobility shift assay (EMSA)
      analysis were employed. RESULTS: The 15d-PGJ2 induced apoptosis in ECV304
      endothelial cells in a dose-dependent manner (the percentage of apoptosis was
      enhanced from 10.0 %+/-1.3 % to 32.8 %+/-1.6 %), which was accompanied by
      inhibition of NF-?B and AP-1 DNA binding activity, down-regulation of c-myc,
      upregulation of Gadd45 and p53, and activation of p38 kinase. However, the
      expression of p21 was found no significant change. CONCLUSION: peroxisome
      proliferator-activated receptor gamma ligand, 15d-PGJ2, can inhibit proliferation
      and induce apoptosis in ECV304 endothelial cells through different mechanisms.

PMID- 14704124
TI  - Inhibition of epidermal growth factor receptor expression by RNA interference in
      A549 cells.
AB  - AIM: To investigate the biological features of A549 cells in which epidermal
      growth factor (EGF) receptors expression were suppressed by RNA interference
      (RNAi). METHODS: A549 cells were transfected using short small interfering RNAs
      (siRNAs) formulated with Lipofectamine 2000. The EGF receptor numbers were
      determined by Western blotting and flowcytometry. The antiproliferative effects
      of sequence specific double stranded RNA (dsRNA) were assessed using cell count,
      colony assay and scratch assay. The chemosensitivity of transfected cells to
      cisplatin was measured by MTT. RESULTS: Sequence specific dsRNA-EGFR down
      regulated EGF receptor expression dramatically. Compared with the control group,
      dsRNA-EGFR reduced the cell number by 85.0 %, decreased the colonies by 63.3 %,
      inhibited the migration by 87.2 %, and increased the sensitivity of A549 to
      cisplatin by four-fold. CONCLUSION: Sequence specific dsRNA-EGFR were capable of
      suppressing EGF receptor expression, hence significantly inhibiting cellular
      proliferation and motility, and enhancing chemosensitivity of A549 cells to
      cisplatin. The successful application of dsRNA-EGFR for inhibition of
      proliferation in EGF receptor overexpressing cells can help extend the list of
      available therapeutic modalities in the treatment of non-small-cell lung
      carcinoma (NSCLC).

PMID- 14704123
TI  - Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its
      relation with AQP1 water channel.
AB  - AIM: To study the effect of topiramate on tumor metastasis and its relation with
      aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model
      was used to determine the effect of topiramate on tumor growth and metastasis.
      Colorimetric estimation was used to investigate the action of topiramate on
      carbonic anhydrase (CA) activity. Western blotting and immunohistochemical
      analysis were used to study the influence of topiramate on AQP1 water channel
      expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.
      RESULTS: Treatment with topiramate (120 mg/kg/d, ig for 20 d) reduced the growth
      of primary tumor significantly (P<0.05). Its inhibitory rate of metastasis was
      81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent
      manner. Topiramate apparently decreased AQP1 protein expression and
      immunostaining in lungs or in tumor microvessel endothelial cells of mice.
      CONCLUSION: Suppression of AQP1 water channel expression may be an important
      pathway for the inhibitory effect of topiramate on tumor metastasis.

PMID- 14704125
TI  - Effects of GM-CSF, IL-3, and GM-CSF/IL-3 fusion protein on apoptosis of human
      myeloid leukemic cell line Tf-1 induced by irradiation.
AB  - AIM: To observe the effects of three cytokines on the apoptosis of Tf-1 cells
      induced by gamma irradiation and investigate the relationship between apoptosis
      and caspase-3 activity. METHODS: Different cytokines GM-CSF, IL-3 and GM-CS/IL-3
      fusion protein were added into the irradiated Tf-1 cells. MTT assay, morphology,
      flow cytometry, and DNA fragmentation assay were used to observe the effects of
      cytokines on apoptosis. The caspase-3 activity was determined with a
      fluorocytometer. RESULTS: Irradiated Tf-1 cells showed typical morphological
      characteristic of apoptosis demonstrated by transmission electron microscopy and
      were accumulated in G0/G1 phase. In the groups treated with growth factors after
      irradiation, three cytokines significantly increased the viability rate,
      distinctly decreased the apoptosis rate and the proportion of DNA fragmentation.
      When Tf-1 cells were irradiated by gamma irradiation, caspase-3 activity was
      increased at different time points. In comparison with the control group in which
      no growth factor was added after the cells were irradiated, the caspase-3
      activity of irradiated Tf-1 cells was significantly inhibited by addition of the
      above cytokines. Thirty-six hours after irradiation, in the control group, GM
      CSF, IL-3, GM-CSF and IL-3 in combination, and two GM-CSF/IL-3 fusion protein
      groups, the apoptosis rate was 73 %, 11 %, 15 %, 13 %, 12 %, and 13 %. The
      percent of fragmented DNA was 36 %, 19 %, 18 %, 14 %, 13 %, and 14 %. The
      fluorescence intensity was 16923, 5529, 6581, 5322, 5426, and 5485. CONCLUSION:
      GM-CSF, IL-3, and GM-CSF/IL-3 fusion protein could protect Tf-1 cells from
      apoptosis induced by gamma irradiation. After Tf-1 cells were irradiated, the
      caspase-3 activity was significantly increased but was dramatically decreased by
      the above cytokines. The remarkable inhibition of caspase-3 activity may be one
      of the mechanisms of these hematopoietic growth factors exerting their anti
      apoptotic effects.

PMID- 14704126
TI  - Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular
      carcinoma Bel7402/5-FU cells.
AB  - AIM: To study the effect of wild type (wt) p53 gene transfection on drug
      resistant human hepatocellular carcinoma (HCC) cells induced by 5-Fluorouracil (5
      FU). METHODS: The cytotoxicity of anticancer drugs on Bel7402 and Bel7402/5-FU
      cells was assessed using SRB assay. p53 expression was detected at its mRNA level
      by RT-PCR assay and at its protein level Western blot or immunocytochemistry
      assay in Bel7402/5-FU cells transfected with either control vector or wt p53.
      AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The
      chemosensitivity of Bel7402/5-FU cells transfected with wt p53 was assessed using
      SRB assay. RESULTS: Bel7402/5-FU cells exhibited cross-resistance to vincristine,
      doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the
      expression of p53 in Bel7402/5-FU cells. wt p53 was able to greatly inhibit cell
      proliferation and significantly induce apoptosis in Bel7402/5-FU cells. Moreover,
      wt p53 gene transfection increased the chemosensitivity of Bel7402/5-FU cells to
      some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene
      transfection not only induced suppression of cell growth, but also increased the
      sensitivity of Bel7402/5-FU cells to 5-FU, vincristine, and doxorubicin.

PMID- 14704128
TI  - Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA
      injected Xenopus oocyte.
AB  - AIM: To study the effects of acetazolamide and anordiol on osmotic water
      permeability in aquaporin 1 (AQP1)-cRNA injected Xenopus oocyte and their
      mechanisms. METHODS: AQP1 gene constructed in pBluescript was transcripted into
      cRNA in vitro and then the cRNA was injected in Xenopus oocytes. The effects of
      acetazolamide and anordiol on the water transport function of AQP1 were observed
      by assaying the osmotic swelling of oocytes. In addition, their effects on
      protein expression of AQP1 were quantitatively investigated by Western blotting
      method. RESULTS: After incubation for 15 min or 72 h, acetazolamide, a carbonic
      anhydrase inhibitor, equally reduced the water permeability of AQP1-cRNA injected
      oocyte in a dose-dependent manner. After incubation for 72 h, anordiol, an
      antiestrogen with partial estrogenic activity, reduced the osmotic water
      permeability dose dependently as well; however, no discernable action was
      observed after incubation with anordiol for 15 min. The Western blotting analysis
      showed that acetazolamide did not influence the protein expression of AQP1.
      However, after incubation for 72 h with anordiol (10 micromol/L), the quantity of
      AQP1 in the oocyte membrane was decreased dramatically (P<0.05). CONCLUSION: Both
      acetazolamide and anordiol inhibited the osmotic water permeability of AQP1-cRNA
      injected oocyte, but their mechanisms were different. Acetazolamide functionally
      inhibited the osmotic water permeability of AQP1, whereas anordiol primarily
      decreased the amount of AQP1 protein in the oocyte membrane.

PMID- 14704127
TI  - Evodiamine induces tumor cell death through different pathways: apoptosis and
      necrosis.
AB  - AIM: To study the different death pathways in human cervical cancer HeLa and
      melanoma A375-S2 cells initiated by evodiamine. METHODS: Viability of evodiamine
      induced HeLa and A375-S2 cells was measured by MTT assay. Apoptotic cells with
      condensed or fragmented nuclei were visualized by Hoechst 33258 staining.
      Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis.
      Proportion of cell death through apoptotic and necrotic pathways was determined
      by LDH activity-based cytotoxicity assays. Cell cycle distribution was observed
      by flow cytometry. RESULTS: Evodiamine induced HeLa and A375-S2 cell death dose-
      and time-dependently. Caspase-3 and -8 were activated in apoptosis induced by
      evodiamine 15 micromol/L. However, over 24-h incubation of A375-S2 cells,
      evodiamine 15 micromol/L initiated necrosis related to p38 and ERK (extracellular
      signal-regulated kinases) activities. Evodiamine-induced HeLa cell death was
      preceded by an accumulation of cells at the G2/M phase of the cell cycle, but
      there was no significant effect of evodiamine on A375-S2 cell cycle. CONCLUSION:
      Evodiamine induces caspase-3,8-dependent apoptosis in HeLa cells which is related
      to G2/M arrest of the cell cycle. On the other hand, in A375-S2 cells, evodiamine
      initiates caspase-3,8-mediated apoptosis at early stages and the induction of
      MAPK-mediated necrosis at later stages of cell culture.

PMID- 14704129
TI  - Inhibitory effect of tea polyphenols on transforming growth factor-beta1
      expression in rat with cyclosporine A-induced chronic nephrotoxicity.
AB  - AIM: To investigate the inhibitory effect of tea polyphenols (TP) on the
      transforming growth factor-beta1 (TGF-beta1) expression in rat model of
      cyclosporine A (CsA)-induced chronic nephrotoxicity. METHODS: The rat model of
      CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively
      treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc)
      and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of
      treatment, serum and urine are analyzed for creatinine clearance, kidney tissue
      for pathologic analysis. The TGF-beta1 mRNA and its protein expression were
      detected by RT-PCR, immunohistochemistry, and Western blot. RESULTS: CsA-treated
      rats had increased renal expression of TGF-beta1 mRNA and its protein, compared
      with the vehicle- or TP-treated controls. The renal function and interstitial
      fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein
      was decreased in animals treated with CsA plus TP, compared with animals treated
      with CsA alone (P<0.05). CONCLUSION: TP significantly inhibits renal expression
      of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity,
      suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one
      of mechanisms to protect renal function and tissue structure.

PMID- 14704130
TI  - Changes of phospholipase D activity of rat peritoneal mast cells in
      degranulation.
AB  - AIM: To study the changes of phospholipase D (PLD) activity of actively
      sensitized rat peritoneal mast cells (RPMC) in degranulation. METHODS:
      Degranulation of RPMC was determined by measurement of beta-hexosaminidase
      release. PLD activity assay was carried out by measurement of PLD product,
      choline, with chemiluminescent oxidation of luminol. RESULTS: Actively sensitized
      RPMC challenged with ovalbumin (0.5-8 mg/L for 120 s, 4 mg/L for 15-120 s)
      resulted in significant activation of PLD accompanied with the increment of beta
      hexosaminidase release. PLD activity of sensitized RPMC was increased by more
      than 2-fold compared with that of unsensitized RPMC which contained low levels of
      PLD activity [(35+/-13) pmol choline/min in 10(6)cells], but beta-hexosaminidase
      releases of the sensitized cells were as low as spontaneous releases. After
      challenge with ovalbumin 4 mg/L for 120 s, PLD activity of sensitized RPMC was
      increased to (155+/-43) pmol choline/min in 10(6)cells and beta-hexosaminidase
      release was also elevated significantly (4.5-fold of spontaneous release, n=6,
      P<0.05). When unsensitized RPMC were stimulated with antigen, PLD activity and
      beta-hexosaminidase release of the cells were hardly changed. Sensitized RPMC
      were treated with 1 % 1-butanol or 2,3- disphosphoglycerate 10 mmol/L before
      challenge with ovalbumin, these drugs induced an inhibition of PLD activity and a
      reduction of beta-hexosaminidase release to basal level. 1-Butanol 0.1 % also
      worked. CONCLUSION: Phospholipase D plays an important role in the regulation of
      beta-hexosaminidase release in actively sensitized rat peritoneal mast cells.

PMID- 14704131
TI  - Simultaneous determination of quetiapine and three metabolites in human plasma by
      high-performance liquid chromatography-electrospray ionization mass spectrometry.
AB  - AIM: To develop a high performance liquid chromatography-electrospray mass
      spectrometry (HPLC-MS/ESI) method for simultaneous determination of quetiapine
      and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in human plasma.
      METHODS: The HPLC separation of the compounds was performed on a Kromasil C18, (5
      microm, 4.6 mm.150 mm) column, using water (formic acid: 1.70 mmol/L, ammonium
      acetate: 5.8 mmol/L)-acetonitrile (65:35) as mobile phase, with a flow-rate of
      0.95 mL/min. The compounds were ionized in the electrospray ionization (ESI) ion
      source of the mass spectrometer and detected in the selected ion recording (SIR)
      mode. The samples were extracted using solid-phase extraction columns. RESULTS:
      The calibration curves were linear in the ranges of 10-2000 microg/L for
      quetiapine, 1-200 microg/L for its metabolites, respectively. The average
      extraction recoveries for all the four samples were above 85 %. The methodology
      recoveries were much higher than 95 %. The intra-day and inter-day RSD are less
      than 15 %. CONCLUSION: The method is accurate, sensitive, and simple for study of
      pharmacokinetics and metabolic mechanism of quetiapine in patients at therapeutic
      dose.

PMID- 14704132
TI  - Effects of ketamine, midazolam, thiopental, and propofol on brain ischemia injury
      in rat cerebral cortical slices.
AB  - AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on
      brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral
      cortical slices. METHODS: Cerebral cortical slices were incubated in 2 % 2,3,5
      triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects
      of ketamine, midazolam, thiopental, and propofol were quantitatively evaluated by
      ELISA reader of absorbance (A) at 490 nm, which indicated the red formazan
      extracted from slices, lactic dehydrogenase (LDH) releases in the incubated
      supernate were also measured. RESULTS: Progressive prolongation of OGD resulted
      in decreases of TTC staining. The percentage of tissue injury had a positive
      correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation
      aggravated the decrease of TTC staining compared with those slices stained
      immediately after OGD (P<0.01). These four anesthetics had no effects on the TTC
      staining of slices. Ketamine completely inhibited the decrease of A value induced
      by 10 min of OGD injury. High concentrations of midazolam (10 micromol/L) and
      thiopental (400 micromol/L) partly attenuated this decrease. Propofol at high
      concentration (100 micromol/L) enhanced the decrease of A value induced by 10 min
      of OGD injury (P<0.01). CONCLUSION: Ketamine, high concentration of midazolam and
      thiopental have neuroprotective effects against OGD injury in rat cerebral
      cortical slices, while high concentration of propofol augments OGD injury in rat
      cerebral cortical slices.

PMID- 14704133
TI  - In vitro identification of metabolites of verapamil in rat liver microsomes.
AB  - AIM: To investigate the metabolism of verapamil at low concentrations in rat
      liver microsomes. METHODS: Liver microsomes of Wistar rats were prepared using
      ultracentrifuge method. The in vitro metabolism of verapamil was studied with the
      rat liver microsomal incubation at concentration of 1.0 micromol/L and 5.0
      micromol/L. The metabolites were separated and assayed by liquid chromatography
      ion trap mass spectrometry (LC/MSn), and further identified by comparison of
      their mass spectra and chromatographic behaviors with reference substances.
      RESULTS: Eight metabolites, including two novel metabolites (M4 and M8), were
      found in rat liver microsomal incubates. They were identified as O-demethyl
      verapamil isomers (M1-M4), N-dealkylated derivatives of verapamil (M5-M7), and
      N,O-didemethyl-verapamil (M8). CONCLUSION: O-Demethylation and N-dealkylation
      were the main metabolic pathways of verapamil at low concentrations in rat liver
      microsomes, and the relative proportion of them in verapamil metabolism changed
      with different substrate concentrations.

PMID- 14704134
TI  - Assessing variation in the radial profile of sap flux density in Pinus species
      and its effect on daily water use.
AB  - We monitored sap flux density (v) diurnally in nine mature southeastern pine
      (Pinus spp.) trees with a thermal dissipation probe that spanned the sapwood
      radius. We found the expected pattern of high v near the cambium and decreasing v
      with depth toward the center of the tree; however, the pattern was not constant
      within a day or between trees. Radial profiles of trees were steeper earlier in
      the day and became less steep later in the day. As a result, time-dependent
      changes in the shape of the radial profile of v were sometimes correlated with
      daily changes in evaporative demand. As the radial profile became less steep, the
      inner xylem contributed relatively more to total tree sap flow than it did
      earlier in the day. We present a 3-parameter Gaussian function that can be used
      to describe the radial distribution of v in trees. Parameters in the function
      represent depth in the xylem from the cambium, maximum v, depth in the xylem
      where maximum v occurs, and the rate of radial change in v with radial depth
      (beta). Values of beta varied significantly between trees and with time, and were
      sometimes correlated with air vapor pressure deficit (D). We hypothesize that
      this occurred during periods of high transpiration when the water potential
      gradient became great enough to move water in the inner sapwood despite its
      probable high hydraulic resistance. We examined discrepancies among estimates of
      daily water use based on single-point, two-point and multi-point (i.e., every 20
      mm in the sapwood) measurements. When radial distribution of v was not
      considered, a single-point measurement resulted in errors as large as 154% in the
      estimate of daily water use relative to the estimate obtained from a multi-point
      measurement. Measuring v at two close sample points (10 and 30 mm) did not
      improve the estimate; however, estimates derived from v measured at two distant
      sample points (10 and 70 mm) significantly improved the estimate of daily water
      use, although errors were as great as 32% in individual trees. The variability in
      v with depth in the xylem, over time, and between trees indicates that
      measurements of the radial distribution of v are necessary to accurately estimate
      water flow in trees with large sapwood areas.

PMID- 14704135
TI  - Induction of anatomically based defense responses in stems of diverse conifers by
      methyl jasmonate: a phylogenetic perspective.
AB  - Conifers have evolved constitutive and inducible defense mechanisms to help in
      both wound healing and defense against attack by bark beetles and other
      organisms. These defenses include oleoresin, phenolics, and static structures in
      secondary phloem, such as lignified cells and calcium oxalate crystals, that
      create physical barriers. We used a phylogenetic approach to investigate the
      defense anatomy of conifer stems of 13 species from five families following
      treatment with methyl jasmonate (MJ), a compound that induces defense responses
      in stems of several Pinaceae species. Methyl jasmonate induced a response similar
      to wounding except that the response was not accompanied by lesion formation,
      necrosis or a hypersensitive response. In the Pinaceae species studied, MJ
      induced polyphenolic parenchyma (PP) cell activation and xylem traumatic resin
      duct (TD) formation. Members of the Taxodiaceae, which are not known to produce
      large quantities of resin, showed massive xylem TD formation and surface
      resinosis following MJ treatment. Treatment with MJ caused members of the
      Araucariaceae and Cupressaceae to form axial phloem resin ducts but not xylem
      ducts, whereas Podocarpaceae species showed no induction of resin-producing
      structures. All species treated with MJ showed phenolic deposition in PP cells,
      and early lignification of phloem fibers was observed in most of the non-Pinaceae
      species. We conclude that, although evolution of resin-producing structures
      occurred independently in conifer lineages, MJ seems to induce resin production
      regardless of tissue location, as well as inducing deposition of phenolic
      compounds. Co-evolution of conifer defensive strategies and bark beetle pests is
      discussed.

PMID- 14704136
TI  - Transcript identification and profiling during salt stress and recovery of
      Populus euphratica.
AB  - Populus euphratica Oli. is a salt-tolerant species that can cope with up to 450
      mM NaCl under hydroponic conditions and can tolerate high accumulations of Na+
      and Cl- in roots and leaves when grown in 300 mM NaCl. Transcript responses to
      salt stress and recovery were monitored by microarray hybridization of 315 cDNAs
      preselected by suppression subtractive hybridization. Transcripts of a heat-shock
      protein and a hydroxyproline-rich glycoprotein accumulated 1.5 and 3 h,
      respectively, after adding 300 mM NaCl to the culture medium. Transcripts
      significantly up-regulated by salt stress included ionic and osmotic homeostasis
      elements such as magnesium transporter-like protein, syntaxin-like protein, seed
      imbibition protein and plasma membrane intrinsic protein; metabolism regulators
      like cytochrome P450, zinc finger protein, cleavage factor and aminotransferase;
      and the photosynthesis-activating enzyme Rubisco activase and photorespiration
      related glycolate oxidase. Several photosynthesis-related transcripts were down
      regulated in response to 72 h of salt stress but were up-regulated after long
      term recovery (48 h). Sucrose synthase, ABC transporter, calmodulin, Pop3 peptide
      and aquaporin appeared to be actively involved in the process of plant recovery
      from salt stress. Several transcripts encoding proteins of unknown function were
      regulated by salt stress. Selected transcripts exhibiting altered transcript
      profiles in response to salt stress were also analyzed by real-time quantitative
      PCR. Transcript analysis during salt stress and recovery of this woody species
      revealed several genes and corresponding proteins deserving special attention in
      future studies of salt tolerance in woody species.

PMID- 14704137
TI  - Ozone uptake, water loss and carbon exchange dynamics in annually drought
      stressed Pinus ponderosa forests: measured trends and parameters for uptake
      modeling.
AB  - This paper describes 3 years of physiological measurements on ponderosa pine
      (Pinus ponderosa Dougl. ex Laws.) growing along an ozone concentration gradient
      in the Sierra Nevada, California, including variables necessary to parameterize,
      validate and modify photosynthesis and stomatal conductance algorithms used to
      estimate ozone uptake. At all sites, gas exchange was under tight stomatal
      control during the growing season. Stomatal conductance was strongly correlated
      with leaf water potential (R2=0.82), which decreased over the growing season with
      decreasing soil water content (R2=0.60). Ozone uptake, carbon uptake, and
      transpirational water loss closely followed the dynamics of stomatal conductance.
      Peak ozone and CO2 uptake occurred in early summer and declined progressively
      thereafter. As a result, periods of maximum ozone uptake did not correspond to
      periods of peak ozone concentration, underscoring the inappropriateness of using
      current metrics based on concentration (e.g., SUM0, W126 and AOT40) for assessing
      ozone exposure risk to plants in this climate region. Both Jmax (maximum CO2
      saturated photosynthetic rate, limited by electron transport) and Vcmax (maximum
      rate of Rubisco-limited carboxylation) increased toward the middle of the growing
      season, then decreased in September. Intrinsic water-use efficiency rose with
      increasing drought stress, as expected. The ratio of Jmax to Vcmax was similar to
      literature values of 2.0. Nighttime respiration followed a Q10 of 2.0, but was
      significantly higher at the high-ozone site. Respiration rates decreased by the
      end of the summer as a result of decreased metabolic activity and carbon stores.

PMID- 14704138
TI  - Influence of climate on radial growth of Pinus cembra within the alpine
      timberline ecotone.
AB  - Radial growth variability and response to interannual climate variation of
      Cembran pine (Pinus cembra L.) were studied in the timberline ecotone on Mt.
      Patscherkofel (2246 m a.s.l.). The study area, which is in the inner alpine dry
      region of the Central Austrian Alps, is characterized by a continental climate
      with minimum precipitation in winter (about 150 mm during December-February) and
      frequent occurrence of warm dry winds (Fohn) in early spring. The hypothesis that
      spatial and temporal variability of radial growth is caused by site-related
      differences in sensitivity to winter stress (i.e., desiccation) was examined by
      applying dendroclimatological techniques. Ordination methods applied to tree ring
      time series revealed that spatial variability in radial growth is influenced by
      the local site factors elevation and slope aspect. Growth-climate relationships
      were explored using Pearson product-moment correlation coefficients and multiple
      regression analysis. Radial growth at the timberline was positively correlated
      with temperature in July and was also strongly correlated with mild temperatures
      in the previous autumn and high precipitation in winter (January-March). At the
      tree line, temperatures in the previous autumn and precipitation in late winter
      (March) also controlled radial growth, whereas July temperature was not
      significantly correlated with ring width. Because previous autumn temperature and
      winter precipitation were the main growth-determining factors at the timberline
      and the tree line, and both of these climate variables are known to influence
      susceptibility of trees to winter stress, the results support the working
      hypothesis. Analysis of climatic conditions in extreme growth years confirmed the
      high sensitivity of tree ring growth to precipitation in late winter (March) at
      the tree line plots. Furthermore, extent of growth reduction and release varied
      spatially and temporarily, with south- and west-facing stands showing a higher
      sensitivity to climate variation in the most recent decade (1990s) than the north
      facing stand. This aspect-related change in sensitivity to climate may be
      associated with effects of climate warming on cambial activity.

PMID- 14704139
TI  - Effects of regulated deficit irrigation during the pre-harvest period on gas
      exchange, leaf development and crop yield of mature almond trees.
AB  - We investigated the effects of regulated deficit irrigation (RDI) during the pre
      harvest period (kernel-filling stage) on water relations, leaf development and
      crop yield in mature almond (Prunus dulcis (Mill.) D.A. Webb cv. Cartagenera)
      trees during a 2-year field experiment. Trees were either irrigated at full-crop
      evapotranspiration (ETc=100%) (well-irrigated control treatment) or subjected to
      an RDI treatment that consisted of full irrigation for the full season, except
      from early June to early August (kernel-filling stage), when 20% ETc was applied.
      The severity of water stress was characterized by measurements of soil water
      content, predawn leaf water potential (Psipd) and relative water content (RWC).
      Stomatal conductance (gs), net CO2 assimilation rate (A), transpiration rate (E),
      leaf abscission, leaf expansion rate and crop yield were also measured. In both
      years, Psipd and RWC of well-irrigated trees were maintained above -1.0 MPa and
      92%, respectively, whereas the corresponding values for trees in the RDI
      treatment were -2.37 MPa and 82%. Long-term water stress led to a progressive
      decline in gs, A and E, with significant reductions after 21 days in the RDI
      treatment. At the time of maximum stress (48 days after commencement of RDI), A,
      gs and E were 64, 67 and 56% lower than control values, respectively. High
      correlations between A, E and gs were observed. Plant water status recovered
      within 15 days after the resumption of irrigation and was associated with
      recovery of soil water content. A relatively rapid and complete recovery of A and
      gs was also observed, although the recovery was slower than for Psipd and RWC.
      Severe water stress during the kernel-filling stage resulted in premature
      defoliation (caused by increased leaf abscission) and a reduction in leaf growth
      rate, which decreased tree leaf area. Although kernel yield was correlated with
      leaf water potential, RDI caused a nonsignificant 7% reduction in kernel yield
      and had no effect on kernel size. The RDI treatment also improved water-use
      efficiency because about 30% less irrigation water was applied in the RDI
      treatment than in the control treatment. We conclude that high-cropping almonds
      can be successfully grown in semiarid regions in an RDI regime provided that
      Psipd is maintained above a threshold value of -2 MPa.

PMID- 14704140
TI  - Does variability in shoot carbon assimilation within the tree crown explain
      variability in peach fruit growth?
AB  - A three-dimensional model of radiative transfer and leaf gas exchange was used to
      quantify daily carbon (C) assimilation of all fruit-bearing shoots (FBS) in an
      early maturing 6-year-old peach tree (Prunus persica L. Batsch) with a heavy crop
      load. For a sample of FBS (n=36), growth of fruit and leafy shoots was measured
      every 1-2 weeks from 24 days after bloom (DAB) until harvest, between 93-101 DAB.
      The objective was to relate shoot C assimilation with harvested fruit mass for
      each shoot to test the hypothesis that variation in C supply contributes
      significantly to variation in fruit growth within and among FBS. Mean C
      assimilation of the sampled shoots was 0.07 g C fruit(-1) day(-1), but varied
      between 0.014 and 0.32 g C fruit(-1) day(-1). This indicates that C availability
      for fruit growth would have varied significantly among individual FBS if they
      were autonomous. Mean fruit dry mass on each FBS varied between 0.716 and 7.68 g
      C at harvest, and most of the variation originated among, not within, individual
      FBS. However, there were no correlations between the mean and standard deviation
      of fruit mass and fruit relative growth rate when each was plotted against shoot
      C assimilation, indicating that factors such as those regulating C demand of
      fruit, or C transfer among individual FBS, may be more important in controlling
      variability in fruit growth than intra-crown variability in shoot C assimilation.
      Under the study conditions, FBS were non-autonomous for C, because a model of
      fruit and leafy shoot growth was unable to reproduce the observed growth without
      supplementary contribution of C from shoots without fruit.

PMID- 14704141
TI  - Effects of elevated carbon dioxide concentration on growth and N2 fixation of
      young Robinia pseudoacacia.
AB  - Effects of elevated CO2 concentration ([CO2]) on carbon (C) and nitrogen (N)
      uptake and N source partitioning (N2 fixation versus mineral soil N uptake) of 1
      year-old Robinia pseudoacacia were determined in a dual 13C and 15N continuous
      labeling experiment. Seedlings were grown for 16 weeks in ambient (350 ppm) or
      elevated [CO2] (700 ppm) with 15NH4 15NO3 as the only mineral nitrogen source.
      Elevated [CO2] increased the fraction of new C in total C, but it did not alter C
      partitioning among plant compartments. Elevated [CO2] also increased the fraction
      of new N in total N and this was coupled with a shift in N source partitioning
      toward N2 fixation. Soil N uptake was unaffected by elevated [CO2], whereas N2
      fixation was markedly increased by the elevated [CO2] treatment, mainly because
      of increased specific fixation (mg N mg(-1) nodule). As a result of increased N2
      fixation, the C/N ratio of tree biomass tended to decrease in the elevated [CO2]
      treatment. Partitioning of N uptake among plant compartments was unaffected by
      elevated [CO2]. Total dry mass of root nodules doubled in response to elevated
      [CO2], but this effect was not significant because of the great variability of
      root nodule formation. Our results show that, in the N2-fixing R. pseudoacacia,
      increased C uptake in response to increased [CO2] is matched by increased N2
      fixation, indicating that enhanced growth in elevated [CO2] might not be
      restricted by N limitations.

PMID- 14704142
TI  - Frost resistance and ice nucleation in leaves of five woody timberline species
      measured in situ during shoot expansion.
AB  - Frost resistance and ice nucleation temperatures of leaves, from bud swelling
      until after full expansion, were measured in situ for five major woody timberline
      species with recently developed field freezing equipment. Frost resistance
      determined in situ on leaves of attached twigs was significantly higher than
      values determined on detached leaves in laboratory tests (e.g., the temperature
      at which incipient frost damage was observed (LTi) was 1.2 degrees C higher for
      detached leaves than for attached leaves of Picea abies (L.) Karst.). Frost
      resistance of leaves of all species changed significantly during shoot expansion
      (e.g., changes of 7.2 and 11 degrees C for Rhododendron ferrugineum L. and Larix
      decidua Mill., respectively). Expanding leaves (between 0 and 60% of full
      expansion) were the most sensitive to frost, with LTi values ranging from -3.4
      degrees C in R. ferrugineum to -6.3 degrees C in L. decidua. Among the studied
      species, P. abies and R. ferrugineum were the most frost sensitive throughout the
      shoot elongation period. In situ freezing patterns of leaves of attached twigs
      also differed from those of leaves of excised twigs. During leaf expansion, two
      distinct freezing exotherms were always registered in situ. The first freezing
      event (E1, high-temperature exotherm) was recorded at -1.5 +/- 0.2 degrees C and
      reflected extracellular ice formation. Exposure of leaves to temperatures at
      which E1 occurred was, in all cases, noninjurious. The low-temperature exotherm
      (E2) mostly coincided with frost damage, except for some stages of leaf expansion
      in R. ferrugineum and P. abies, indicating that in situ freezing exotherms were
      not accurate estimators of frost damage in these species.

PMID- 14704143
TI  - Distribution and partial characterization of seasonally expressed proteins in
      different aged shoots and roots of 'Loring' peach (Prunus persica).
AB  - During autumnal leaf senescence, leaf nitrogen in deciduous trees is translocated
      to storage sites, especially bark and xylem tissues. Proteins that accumulate in
      large amounts in bark and xylem in winter and are absent from these organs in
      summer are called storage proteins, and are believed to be vehicles for storing
      nitrogen reserves. These reserves are important for spring growth and help trees
      tolerate or recover from both abiotic and biotic stresses. Based on seasonal
      patterns of accumulation, we previously identified three storage proteins with
      molecular masses of 60, 19 and 16 kDa in bark tissues of 'Loring' peach (Prunus
      persica (L.) Batsch). To characterize the distribution of these proteins in
      different-aged tissues and to determine if they have any function other than
      nitrogen storage, we examined their seasonal distribution in bark tissues of
      current-year and 1-year-old shoots, scaffold branches, main trunks and 4-5-year
      old roots of 'Loring' peach. Verification of protein identity was based on
      molecular mass and reactions with antibodies directed against each specific
      protein. Protein distribution was variable. For all three proteins, the greatest
      amount was present in mid-winter in current-year and 1-year-old shoots. These
      tissues also showed the greatest seasonal variation in the amount of protein
      present. The 16 kDa protein was present only in the youngest shoots, whereas the
      19 kDa protein was present in all tissues examined. The 60 kDa protein was absent
      in root tissue. The amino acid composition and sequence of each protein were
      determined. The 60 kDa protein was identified as a dehydrin, and the 19 kDa
      protein appeared to be related to a family of allergen proteins in Rosaceous
      plants, some members of which are associated with pathogenesis-related proteins.
      The amino acid sequence of the 16 kDa protein appeared to have no homology with
      any proteins in the SwissProt database. Therefore, it is likely that the 16 kDa
      protein, in a strict sense, is a bark storage protein. Defining storage proteins
      solely by their pattern of accumulation and the extent to which they accumulate
      may not be a good functional definition. It is possible that storage proteins
      have functional roles in addition to nitrogen storage.

PMID- 14704144
TI  - Variations in dark respiration and mitochondrial numbers within needles of Pinus
      radiata grown in ambient or elevated CO2 partial pressure.
AB  - Within-leaf variations in cell size, mitochondrial numbers and dark respiration
      rates were compared in the most recently expanded tip, the mid-section and base
      of needles of Pinus radiata D. Don trees grown for 4 years in open-top chambers
      at ambient (36 Pa) or elevated (65 Pa) carbon dioxide partial pressure (p(CO2)a).
      Mitochondrial numbers and respiratory activity varied along the length of the
      needle, with the highest number of mitochondria per unit cytoplasm and the
      highest rate of respiration per unit leaf area at the base of the needle.
      Regardless of the location of the cells (tip, middle or basal sections), needles
      collected from trees grown in elevated p(CO2)a had nearly twice the number of
      mitochondria per unit cytoplasm as those grown in ambient p(CO2)a. This
      stimulation of mitochondrial density by growth at elevated p(CO2)a was greater at
      the tip of the needle (2.7 times more mitochondria than in needles grown in
      ambient CO2) than at the base of the needle (1.7 times). The mean size of
      individual mitochondria was unaffected either by growth at elevated p(CO2)a or by
      position along the needle. Tree growth at elevated p(CO2)a had a variable effect
      on respiration per unit leaf area, significantly increasing respiration in the
      tip of the needles (+25%) and decreasing respiration at the mid-section and base
      of the needles (-14% and -25%, respectively). Although a simple relationship
      between respiration per unit leaf area and mitochondrial number per unit
      cytoplasm was found within each CO2 treatment, the variable effect of growth at
      elevated p(CO2)a on respiration along the length of the needles indicates that a
      more complex relationship must determine the association between structure and
      function in these needles.

PMID- 14704145
TI  - Nitrogen mobilization, nitrogen uptake and growth of cuttings obtained from
      poplar stock plants grown in different N regimes and sprayed with urea in autumn.
AB  - Nitrogen mobilization, nitrogen uptake and growth of cuttings obtained from
      poplar stock plants fertigated with different nitrogen (N) treatments and sprayed
      with urea in autumn were studied. Stock plants propagated from poplar cuttings
      were trained to a single shoot and fertigated with 0, 5, 10, 15 or 20 mmol l(-1)
      N during the first growing season. In October, a subset of stock plants from each
      N fertigation treatment was sprayed twice with either 3% urea or water, and
      overwintered outside. In March, total tree biomass and total N concentration and
      content of stems were estimated for stock plants in each treatment, and cuttings
      were taken from the middle of each stock plant and stored in plastic bags at 2
      degrees C. In mid-April, cuttings were planted in 7.5-l pots containing N-free
      medium and grown outdoors with a weekly fertigation with nutrient solution
      containing 0 or 10 mmol l(-1) 15NH4 15NO3. In mid-July, cuttings were harvested,
      and new shoot (new stems and leaves), shank (old cutting stem) and roots were
      analyzed for new biomass growth and total N and 15N content. Growth of stock
      plants was positively related to N supply in the previous growing season. Foliar
      urea application in autumn had no effect on subsequent stock plant growth even
      though urea sprays increased both N concentration and content in stem tissues.
      Biomass growth of cuttings obtained from stock plants was closely related to
      their N content when the cuttings were grown in an N-free medium regardless of
      previous treatments applied to the stock plants. When N was supplied in the
      growth medium, the strength of the relationship between regrowth and N content of
      cuttings was significantly reduced. Cuttings from stock plants treated with
      foliar urea and grown in a N-free medium remobilized between 75 and 82% of their
      total N for new growth, whereas cuttings from plants receiving no urea spray
      remobilized only between 60 and 69% of their total N for new growth. Current N
      fertilization of the cuttings reduced the percentage of N remobilized. We
      conclude that new growth of poplar cuttings in spring was more dependent on
      currently applied N than on reserve N, and urea N applied as a spray in autumn
      was more easily remobilized than N taken up by roots during the previous season.

PMID- 14704146
TI  - Direct binding of neutral endopeptidase 24.11 to ezrin/radixin/moesin (ERM)
      proteins competes with the interaction of CD44 with ERM proteins.
AB  - Neutral endopeptidase 24.11 (NEP) is a cell surface peptidase expressed by
      numerous tissues including prostatic epithelial cells. We reported that NEP
      inhibits prostate cancer cell proliferation and cell migration by enzymatic
      inactivation of neuropeptide substrates and through protein-protein interaction
      independent of catalytic function. The cytoplasmic domain of NEP contains a
      positively charged amino acid cluster, previously identified as a binding site
      for ezrin/radixin/moesin (ERM) proteins. We report here that NEP co
      immunoprecipitates with ERM proteins in NEP-expressing LNCaP prostate cancer
      cells and MeWo melanoma cells. Co-immunoprecipitation showed that ERM proteins
      associate with wild-type NEP protein but not NEP protein containing a truncated
      cytoplasmic domain or point mutations replacing the positively charged amino acid
      cluster. In vitro binding assays showed that NEP binds directly to recombinant N
      terminus fragments of ERM proteins at the positively charged amino acid cluster
      within the NEP cytoplasmic domain. Binding of ERM proteins to NEP results in
      decreased binding of ERM proteins to the hyaluronan receptor CD44, a main binding
      partner of ERM proteins. Moreover, cells expressing wild-type NEP demonstrate
      decreased adhesion to hyaluronic acid and cell migration. These data suggest that
      NEP can affect cell adhesion and migration through direct binding to ERM
      proteins.

PMID- 14704147
TI  - Inhibition of cell proliferation and cell cycle progression by specific
      inhibition of basal JNK activity: evidence that mitotic Bcl-2 phosphorylation is
      JNK-independent.
AB  - The c-Jun NH(2)-terminal kinase (JNK) subgroup of mitogen-activated protein
      kinases has been implicated largely in stress responses, but an increasing body
      of evidence has suggested that JNK also plays a role in cell proliferation and
      survival. We examined the effect of JNK inhibition, using either SP600125 or
      specific antisense oligonucleotides, on cell proliferation and cell cycle
      progression. SP600125 was selective for JNK in vitro and in vivo versus other
      kinases tested including ERK, p38, cyclin-dependent protein kinase 1 (CDK1), and
      CDK2. SP600125 inhibited JNK activity and KB-3 cell proliferation with the same
      dose dependence, suggesting that inhibition of proliferation was a direct
      consequence of JNK inhibition. Inhibition of proliferation by SP600125 was
      associated with an increase in the G(2)-M and apoptotic fractions of cells but
      was not associated with p53 or p21 induction. Antisense oligonucleotides to JNK2
      but not JNK1 caused highly significant inhibition of cell proliferation. Wild
      type mouse fibroblasts responded similarly with proliferation inhibition and
      apoptosis induction, whereas c-jun(-/-) fibroblasts were refractory to the
      effects of SP600125, suggesting that JNK signaling to c-Jun is required for cell
      proliferation. Studies in synchronized KB-3 cells indicated that SP600125 delayed
      transit time through S and G(2)-M phases. Correspondingly, JNK activity increased
      in late S phase and peaked in late G(2) phase. During synchronous mitotic
      progression, cyclin B levels increased concomitant with phosphorylation of c-Jun,
      H1 histone, and Bcl-2. In the presence of SP600125, mitotic progression was
      prolonged, and c-Jun phosphorylation was inhibited, but neither H1 nor Bcl-2
      phosphorylation was inhibited. However, the CDK inhibitor roscovitine inhibited
      mitotic Bcl-2 phosphorylation. These results indicate that JNK, and more
      specifically the JNK2 isoform, plays a key role in cell proliferation and cell
      cycle progression. In addition, conclusive evidence is presented that a kinase
      other than JNK, most likely CDK1 or a CDK1-regulated kinase, is responsible for
      mitotic Bcl-2 phosphorylation.

PMID- 14704148
TI  - The peroxisome proliferator-activated receptor gamma regulates expression of the
      perilipin gene in adipocytes.
AB  - Recent studies have shown that lipid droplets are covered with a proteinaceous
      coat, although the functions and identities of the component proteins have not
      yet been well elucidated. The first identified lipid droplet-specific proteins
      are the perilipins, a family of proteins coating the surfaces of lipid droplets
      of adipocytes. The generation of perilipin-null mice has revealed that although
      they consume more food than control mice, they have normal body weight and are
      resistant to diet-induced obesity. In one study (Martinez-Botas, J., Anderson, J.
      B., Tessier, D., Lapillonne, A., Chang, B. H. J., Quast, M. J., Gorenstein, D.,
      Chen, K. H., and Chan, L. (2000) Nat. Genet. 26, 474-479) it was reported that in
      an animal model obesity was reversible by breeding perilipin -/- alleles into
      Lepr db/db obese mice, ostensibly by increasing the metabolic rate of the mice.
      To understand the exact mechanisms that drive the exclusive expression of the
      perilipin gene in adipocytes, we analyzed the 5'-flanking region of the mouse
      gene. Treatment of differentiating 3T3-L1 adipocytes with an agonist of
      proliferator-activated receptor (PPAR) gamma, the putative "master regulator" of
      adipocyte differentiation, significantly augmented perilipin gene expression.
      Reporter assays using the -2.0-kb promoter revealed that this region contains a
      functional PPARgamma-responsive element. Gel mobility shift and chromatin
      immunoprecipitation assays showed that endogenous PPARgamma protein binds to the
      perilipin promoter. PPARgamma2, an isoform exclusively expressed in adipocytes,
      was found to be the most potent regulator from among the PPAR family members
      including PPARalpha and PPARgamma1. These results make evident the fact that
      perilipin gene expression in differentiating adipocytes is crucially regulated by
      PPARgamma2, providing new insights into the adipogenic action of PPARgamma2 and
      adipose-specific gene expression, as well as potential anti-obesity
      pharmaceutical agents targeted to a reduction of the perilipin gene product.

PMID- 14704149
TI  - Signal peptide peptidase forms a homodimer that is labeled by an active site
      directed gamma-secretase inhibitor.
AB  - Presenilin (PS) is the presumptive catalytic component of the intramembrane
      aspartyl protease gamma-secretase complex. Recently a family of presenilin
      homologs was identified. One member of this family, signal peptide peptidase
      (SPP), has been shown to be a protease, which supports the hypothesis that PS and
      presenilin homologs are related intramembrane-cleaving aspartyl proteases. SPP
      has been reported as a glycoprotein of approximately 45 kDa. Our initial
      characterization of SPP isolated from human brain and cell lines demonstrated
      that SPP is primarily present as an SDS-stable approximately 95-kDa protein on
      Western blots. Upon heating or treatment of this approximately 95-kDa SPP band
      with acid, a approximately 45-kDa band could be resolved. Co-purification of two
      different epitope-tagged forms of SPP from a stably transfected cell line
      expressing both tagged versions demonstrated that the approximately 95-kDa band
      is a homodimer of SPP. Pulse-chase metabolic labeling studies demonstrated that
      the SPP homodimer assembles rapidly and is metabolically stable. In a glycerol
      velocity gradient, SPP sedimented from approximately 100-200 kDa. Significantly
      the SPP homodimer was specifically labeled by an active site-directed
      photoaffinity probe (III-63) for PS, indicating that the active sites of SPP and
      PS/gamma-secretase are similar and providing strong evidence that the homodimer
      is functionally active. Collectively these data suggest that SPP exists in vivo
      as a functional dimer.

PMID- 14704150
TI  - Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen
      activator through c-Src-dependent epidermal growth factor receptor
      transactivation in breast cancer cells.
AB  - We have recently reported that osteopontin (OPN) stimulates cell motility and
      nuclear factor kappaB-mediated secretion of urokinase-type plasminogen activator
      (uPA) through phosphatidylinositol 3-kinase/Akt signaling pathways in breast
      cancer cells (Das, R., Mahabeleshwar, G. H., and Kundu, G. C. (2003) J. Biol.
      Chem. 278, 28593-28606). However, the role(s) of OPN on AP-1-mediated uPA
      secretion and cell motility and the involvement of c-Src/epidermal growth factor
      receptor (EGFR) in these processes in breast cancer cells are not well defined.
      In this study we report that OPN induces alpha(v)beta(3) integrin-mediated c-Src
      kinase activity in both highly invasive (MDA-MB-231) and low invasive (MCF-7)
      breast cancer cells. Ligation of OPN with alpha(v)beta(3) integrin induces kinase
      activity and tyrosine phosphorylation of EGFR in MDA-MB-231 and wild type EGFR
      transfected MCF-7 cells, and this was inhibited by the dominant negative form of
      c-Src (dn c-Src) indicating that c-Src kinase plays a crucial role in this
      process. OPN induces association between alpha(v)beta(3) integrin and EGFR on the
      cell membrane in a macromolecular form with c-Src. Furthermore, OPN induces
      alpha(v)beta(3) integrin/EGFR-mediated ERK1/2 phosphorylation and AP-1
      activation. Moreover, dn c-Src also suppressed the OPN-induced
      phosphatidylinositol (PI) 3-kinase activity in these cells indicating that c-Src
      acts as master switch in regulating MEK/ERK1/2 and phosphatidylinositol 3
      kinase/Akt signaling pathways. OPN-induced ERK phosphorylation, AP-1 activation,
      uPA secretion, and cell motility were suppressed when cells were transfected with
      dn c-Src or pretreated with alpha(v)beta(3) integrin antibody, c-Src kinase
      inhibitor (pp2), EGFR tyrosine kinase inhibitor (PD153035), and MEK-1 inhibitor
      (PD98059). To our knowledge, this is the first report that OPN induces
      alpha(v)beta(3) integrin-mediated AP-1 activity and uPA secretion by activating c
      Src/EGFR/ERK signaling pathways and further demonstrates a functional molecular
      link between OPN-induced integrin/c-Src-dependent EGFR phosphorylation and ERK/AP
      1-mediated uPA secretion, and all of these ultimately control the motility of
      breast cancer cells.

PMID- 14704151
TI  - Nitrosyl-heme complexes are formed in the ischemic heart: evidence of nitrite
      derived nitric oxide formation, storage, and signaling in post-ischemic tissues.
AB  - In addition to the generation from specific nitric-oxide (NO) synthases, NO
      formation from nitrite occurs in ischemic tissues, such as the heart. Although NO
      binding to heme-centers is the basis for NO-mediated signaling as occurs through
      guanylate cyclase, it is not known if this process is triggered with
      physiologically relevant periods of sublethal ischemia and if nitrite serves as a
      critical substrate. Therefore electron paramagnetic resonance studies were
      performed to measure nitrosylheme formation during the time course of myocardial
      ischemia and reperfusion and the role of nitrite in this process. Rat hearts were
      either partially nitrite-depleted by nitrite-free buffer perfusion or nitrite
      enriched by preinfusion with 50 microm nitrite. Ischemic hearts loaded with
      nitrite showed prominent spectra of six-coordinate nitrosyl-heme complexes,
      primarily NO-myoglobin, that increased as a function of ischemic duration,
      whereas in nonischemic-controls these signals were not seen. Total nitrosyl-heme
      concentrations within the heart were 6.6 +/- 0.7 microm after 30 min of ischemia.
      Nitrite-depleted hearts also gave rise to NO-heme signals during ischemia, but
      levels were 8-fold lower. Nitrite-mediated NO-heme complex formation during
      ischemia was associated with activation of guanylate cyclase. Upon reperfusion,
      the levels of NO-heme complexes decreased 3-fold by the first 15 min but remained
      elevated for over 45 min. The decrease in NO-heme complex levels was paralleled
      by the formation of nitrate, suggesting the oxidation of heme-bound NO upon
      reperfusion. Thus, nitrite-mediated NO-heme formation occurs progressively during
      ischemia, with these complexes serving as a store of NO with concordant
      activation of NO signaling pathways.

PMID- 14704152
TI  - Human amylin oligomer growth and fibril elongation define two distinct phases in
      amyloid formation.
AB  - Human amylin (hA), a 37-amino-acid polypeptide, is one of a number of peptides
      with the ability to form amyloid fibrils and cause disease. It is the main
      constituent of the pancreatic amyloid deposits associated with type 2 diabetes.
      Increasing interest in early assembly intermediates rather than the mature
      fibrils as the cytotoxic agent has led to this study in which the smallest hA
      oligomers have been captured by atomic force microscopy. These are 2.3 +/- 1.9 nm
      in height, 23 +/- 14 nm in length, and consist of an estimated 16 hA molecules.
      Oligomers first grow to a height of about 6 nm before they begin to significantly
      elongate into fibrils. Congo red inhibits elongation but not the growth in height
      of hA oligomers. Two distinct phases have thus been identified in hA
      fibrillogenesis: lateral growth of oligomers followed by longitudinal growth into
      mature fibrils. These observations suggest that mature fibrils are assembled
      directly via longitudinal growth of full-width oligomers, making assembly by
      lateral association of protofibrils appear less likely.

PMID- 14704153
TI  - Structural insights into molecular function of the metastasis-associated
      phosphatase PRL-3.
AB  - Phosphatases and kinases are the cellular signal transduction enzymes that
      control protein phosphorylation. PRL phosphatases constitute a novel class of
      small (20 kDa), prenylated phosphatases with oncogenic activity. In particular,
      PRL-3 is consistently overexpressed in liver metastasis in colorectal cancer
      cells and represents a new therapeutic target. Here, we present the solution
      structure of PRL-3, the first structure of a PRL phosphatase. The structure
      places PRL phosphatases in the class of dual specificity phosphatases with
      closest structural homology to the VHR phosphatase. The structure, coupled with
      kinetic studies of site-directed mutants, identifies functionally important
      residues and reveals unique features, differentiating PRLs from other
      phosphatases. These differences include an unusually hydrophobic active site
      without the catalytically important serine/threonine found in most other
      phosphatases. The position of the general acid loop indicates the presence of
      conformational change upon catalysis. The studies also identify a potential
      regulatory role of Cys(49) that forms an intramolecular disulfide bond with the
      catalytic Cys(104) even under mildly reducing conditions. Molecular modeling of
      the highly homologous PRL-1 and PRL-2 phosphatases revealed unique surface
      elements that are potentially important for specificity.

PMID- 14704154
TI  - RNA processing: a postdoc in a great laboratory.

PMID- 14704155
TI  - Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12.
AB  - Although plasmids can provide beneficial functions to their host bacteria, they
      might confer a physiological or energetic cost. This study examines how natural
      selection may reduce the cost of carrying conjugative plasmids with drug
      resistance markers in the absence of antibiotic selection. We studied two
      plasmids, R1 and RP4, both of which carry multiple drug resistance genes and were
      shown to impose an initial fitness cost on Escherichia coli. To determine if and
      how the cost could be reduced, we subjected plasmid-containing bacteria to 1100
      generations of evolution in batch cultures. Analysis of the evolved populations
      revealed that plasmid loss never occurred, but that the cost was reduced through
      genetic changes in both the plasmids and the bacteria. Changes in the plasmids
      were inferred by the demonstration that evolved plasmids no longer imposed a cost
      on their hosts when transferred to a plasmid-free clone of the ancestral E. coli.
      Changes in the bacteria were shown by the lowered cost when the ancestral
      plasmids were introduced into evolved bacteria that had been cured of their
      (evolved) plasmids. Additionally, changes in the bacteria were inferred because
      conjugative transfer rates of evolved R1 plasmids were lower in the evolved host
      than in the ancestral host. Our results suggest that once a conjugative bacterial
      plasmid has invaded a bacterial population it will remain even if the original
      selection is discontinued.

PMID- 14704156
TI  - A conservative test of genetic drift in the endosymbiotic bacterium Buchnera:
      slightly deleterious mutations in the chaperonin groEL.
AB  - The obligate endosymbiotic bacterium Buchnera aphidicola shows elevated rates of
      sequence evolution compared to free-living relatives, particularly at
      nonsynonymous sites. Because Buchnera experiences population bottlenecks during
      transmission to the offspring of its aphid host, it is hypothesized that genetic
      drift and the accumulation of slightly deleterious mutations can explain this
      rate increase. Recent studies of intraspecific variation in Buchnera reveal
      patterns consistent with this hypothesis. In this study, we examine inter- and
      intraspecific nucleotide variation in groEL, a highly conserved chaperonin gene
      that is constitutively overexpressed in Buchnera. Maximum-likelihood estimates of
      nonsynonymous substitution rates across Buchnera species are strikingly low at
      groEL compared to other loci. Despite this evidence for strong purifying
      selection on groEL, our intraspecific analysis of this gene documents reduced
      synonymous polymorphism, elevated nonsynonymous polymorphism, and an excess of
      rare alleles relative to the neutral expectation, as found in recent studies of
      other Buchnera loci. Comparisons with Escherichia coli generally show patterns
      predicted by their differences in N(e). The sum of these observations is not
      expected under relaxed or balancing selection, selective sweeps, or increased
      mutation rate. Rather, they further support the hypothesis that drift is an
      important force driving accelerated protein evolution in this obligate mutualist.

PMID- 14704157
TI  - The Sla2p talin domain plays a role in endocytosis in Saccharomyces cerevisiae.
AB  - Clathrin-binding adaptors play critical roles for endocytosis in multicellular
      organisms, but their roles in budding yeast have remained unclear. To address
      this question, we created a quadruple mutant yeast strain lacking the genes
      encoding the candidate clathrin adaptors Yap1801p, Yap1802p, and Ent2p and
      containing a truncated version of Ent1p, Ent1DeltaCBMp, missing its clathrin
      binding motif. This strain was viable and competent for endocytosis, suggesting
      the existence of other redundant adaptor-like factors. To identify these factors,
      we mutagenized the quadruple clathrin adaptor mutant strain and selected cells
      that were viable in the presence of full-length Ent1p, but inviable with only
      Ent1DeltaCBMp; these strains were named Rcb (requires clathrin binding). One
      mutant strain, rcb432, contained a mutation in SLA2 that resulted in lower levels
      of a truncated protein lacking the F-actin binding talin homology domain.
      Analyses of this sla2 mutant showed that the talin homology domain is required
      for endocytosis at elevated temperature, that SLA2 exhibits genetic interactions
      with both ENT1 and ENT2, and that the clathrin adaptors and Sla2p together
      regulate the actin cytoskeleton and revealed conditions under which Yap1801p and
      Yap1802p contribute to viability. Together, our data support the view that Sla2p
      is an adaptor that links actin to clathrin and endocytosis.

PMID- 14704158
TI  - Destabilizing interactions among [PSI(+)] and [PIN(+)] yeast prion variants.
AB  - The yeast Sup35 and Rnq1 proteins can exist in either the noninfectious soluble
      forms, [psi-] or [pin-], respectively, or the multiple infectious amyloid-like
      forms called [PSI+] or [PIN+] prion variants (or prion strains). It was
      previously shown that [PSI+] and [PIN+] prions enhance one another's de novo
      appearance. Here we show that specific prion variants of [PSI+] and [PIN+]
      disrupt each other's stable inheritance. Acquiring [PSI+] often impedes the
      inheritance of particular [PIN+] variants. Conversely, the presence of some
      [PIN+] variants impairs the inheritance of weak [PSI+] but not strong [PSI+]
      variants. These same [PIN+] variants generate a single-dot fluorescence pattern
      when a fusion of Rnq1 and green fluorescent protein is expressed. Another [PIN+]
      variant, which forms a distinctly different multiple-dot fluorescence pattern,
      does not impair [PSI+] inheritance. Thus, destabilization of prions by
      heterologous prions depends upon the variants involved. These findings may have
      implications for understanding interactions among other amyloid-forming proteins,
      including those associated with certain human diseases.

PMID- 14704159
TI  - The ESS1 prolyl isomerase and its suppressor BYE1 interact with RNA pol II to
      inhibit transcription elongation in Saccharomyces cerevisiae.
AB  - Transcription by RNA polymerase II (pol II) requires the ordered binding of
      distinct protein complexes to catalyze initiation, elongation, termination, and
      coupled mRNA processing events. One or more proteins from each complex are known
      to bind pol II via the carboxy-terminal domain (CTD) of the largest subunit,
      Rpb1. How binding is coordinated is not known, but it might involve
      conformational changes in the CTD induced by the Ess1 peptidyl-prolyl cis/trans
      isomerase. Here, we examined the role of ESS1 in transcription by studying one of
      its multicopy suppressors, BYE1. We found that Bye1 is a negative regulator of
      transcription elongation. This led to the finding that Ess1 also inhibits
      elongation; Ess1 opposes elongation factors Dst1 and Spt4/5, and overexpression
      of ESS1 makes cells more sensitive to the elongation inhibitor 6-AU. In reporter
      gene assays, ess1 mutations reduce the ability of elongation-arrest sites to
      stall polymerase. We also show that Ess1 acts positively in transcription
      termination, independent of its role in elongation. We propose that Ess1-induced
      conformational changes attenuate pol II elongation and help coordinate the
      ordered assembly of protein complexes on the CTD. In this way, Ess1 might
      regulate the transition between multiple steps of transcription.

PMID- 14704160
TI  - The N-terminal DNA-binding domain of Rad52 promotes RAD51-independent
      recombination in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the Rad52 protein plays a role in both RAD51
      dependent and RAD51-independent recombination pathways. We characterized a rad52
      mutant, rad52-329, which lacks the C-terminal Rad51-interacting domain, and
      studied its role in RAD51-independent recombination. The rad52-329 mutant is
      completely defective in mating-type switching, but partially proficient in
      recombination between inverted repeats. We also analyzed the effect of the rad52
      329 mutant on telomere recombination. Yeast cells lacking telomerase maintain
      telomere length by recombination. The rad52-329 mutant is deficient in RAD51
      dependent telomere recombination, but is proficient in RAD51-independent telomere
      recombination. In addition, we examined the roles of other recombination genes in
      the telomere recombination. The RAD51-independent recombination in the rad52-329
      mutant is promoted by a paralogue of Rad52, Rad59. All components of the Rad50
      Mre11-Xrs2 complex are also important, but not essential, for RAD51-independent
      telomere recombination. Interestingly, RAD51 inhibits the RAD51-independent,
      RAD52-dependent telomere recombination. These findings indicate that Rad52
      itself, and more precisely its N-terminal DNA-binding domain, promote an
      essential reaction in recombination in the absence of RAD51.

PMID- 14704161
TI  - Functions of Saccharomyces cerevisiae 14-3-3 proteins in response to DNA damage
      and to DNA replication stress.
AB  - Two members of the 14-3-3 protein family, involved in key biological processes in
      different eukaryotes, are encoded by the functionally redundant Saccharomyces
      cerevisiae BMH1 and BMH2 genes. We produced and characterized 12 independent bmh1
      mutant alleles, whose presence in the cell as the sole 14-3-3 source causes
      hypersensitivity to genotoxic agents, indicating that Bmh proteins are required
      for proper response to DNA damage. In particular, the bmh1-103 and bmh1-266
      mutant alleles cause defects in G1/S and G2/M DNA damage checkpoints, whereas
      only the G2/M checkpoint is altered by the bmh1-169 and bmh1-221 alleles.
      Impaired checkpoint responses correlate with the inability to maintain
      phosphorylated forms of Rad53 and/or Chk1, suggesting that Bmh proteins might
      regulate phosphorylation/dephosphorylation of these checkpoint kinases. Moreover,
      several bmh1 bmh2Delta mutants are defective in resuming DNA replication after
      transient deoxynucleotide depletion, and all display synthetic effects when also
      carrying mutations affecting the polalpha-primase and RPA DNA replication
      complexes, suggesting a role for Bmh proteins in DNA replication stress response.
      Finally, the bmh1-169 bmh2Delta and bmh1-170 bmh2Delta mutants show increased
      rates of spontaneous gross chromosomal rearrangements, indicating that Bmh
      proteins are required to suppress genome instability.

PMID- 14704162
TI  - Role of mismatch repair in the fidelity of RAD51- and RAD59-dependent
      recombination in Saccharomyces cerevisiae.
AB  - To prevent genome instability, recombination between sequences that contain
      mismatches (homeologous recombination) is suppressed by the mismatch repair (MMR)
      pathway. To understand the interactions necessary for this regulation, the
      genetic requirements for the inhibition of homeologous recombination were
      examined using mutants in the RAD52 epistasis group of Saccharomyces cerevisiae.
      The use of a chromosomal inverted-repeat recombination assay to measure
      spontaneous recombination between 91 and 100% identical sequences demonstrated
      differences in the fidelity of recombination in pathways defined by their
      dependence on RAD51 and RAD59. In addition, the regulation of homeologous
      recombination in rad51 and rad59 mutants displayed distinct patterns of
      inhibition by different members of the MMR pathway. Whereas the requirements for
      the MutS homolog, MSH2, and the MutL homolog, MLH1, in the suppression of
      homeologous recombination were similar in rad51 strains, the loss of MSH2 caused
      a greater loss in homeologous recombination suppression than did the loss of MLH1
      in a rad59 strain. The nonequivalence of the regulatory patterns in the wild-type
      and mutant strains suggests an overlap between the roles of the RAD51 and RAD59
      gene products in potential cooperative recombination mechanisms used in wild-type
      cells.

PMID- 14704163
TI  - Genome-wide amplifications caused by chromosomal rearrangements play a major role
      in the adaptive evolution of natural yeast.
AB  - The relative importance of gross chromosomal rearrangements to adaptive evolution
      has not been precisely defined. The Saccharomyces cerevisiae flor yeast strains
      offer significant advantages for the study of molecular evolution since they have
      recently evolved to a high degree of specialization in a very restrictive
      environment. Using DNA microarray technology, we have compared the genomes of two
      prominent variants of S. cerevisiae flor yeast strains. The strains differ from
      one another in the DNA copy number of 116 genomic regions that comprise 38% of
      the genome. In most cases, these regions are amplicons flanked by repeated
      sequences or other recombination hotspots previously described as regions where
      double-strand breaks occur. The presence of genes that confer specific
      characteristics to the flor yeast within the amplicons supports the role of
      chromosomal rearrangements as a major mechanism of adaptive evolution in S.
      cerevisiae. We propose that nonallelic interactions are enhanced by ethanol- and
      acetaldehyde-induced double-strand breaks in the chromosomal DNA, which are
      repaired by pathways that yield gross chromosomal rearrangements. This mechanism
      of chromosomal evolution could also account for the sexual isolation shown among
      the flor yeast.

PMID- 14704164
TI  - Polymorphism, recombination and alternative unscrambling in the DNA polymerase
      alpha gene of the ciliate Stylonychia lemnae (Alveolata; class Spirotrichea).
AB  - DNA polymerase alpha is the most highly scrambled gene known in stichotrichous
      ciliates. In its hereditary micronuclear form, it is broken into >40 pieces on
      two loci at least 3 kb apart. Scrambled genes must be reassembled through
      developmental DNA rearrangements to yield functioning macronuclear genes, but the
      mechanism and accuracy of this process are unknown. We describe the first
      analysis of DNA polymorphism in the macronuclear version of any scrambled gene.
      Six functional haplotypes obtained from five Eurasian strains of Stylonychia
      lemnae were highly polymorphic compared to Drosophila genes. Another incompletely
      unscrambled haplotype was interrupted by frameshift and nonsense mutations but
      contained more silent mutations than expected by allelic inactivation. In our
      sample, nucleotide diversity and recombination signals were unexpectedly high
      within a region encompassing the boundary of the two micronuclear loci. From this
      and other evidence we infer that both members of a long repeat at the ends of the
      loci provide alternative substrates for unscrambling in this region. Incongruent
      genealogies and recombination patterns were also consistent with separation of
      the two loci by a large genetic distance. Our results suggest that ciliate
      developmental DNA rearrangements may be more probabilistic and error prone than
      previously appreciated and constitute a potential source of macronuclear
      variation. From this perspective we introduce the nonsense-suppression hypothesis
      for the evolution of ciliate altered genetic codes. We also introduce methods and
      software to calculate the likelihood of hemizygosity in ciliate haplotype samples
      and to correct for multiple comparisons in sliding-window analyses of Tajima's D.

PMID- 14704165
TI  - The divergent orphan nuclear receptor ODR-7 regulates olfactory neuron gene
      expression via multiple mechanisms in Caenorhabditis elegans.
AB  - Nuclear receptors regulate numerous critical biological processes. The C. elegans
      genome is predicted to encode approximately 270 nuclear receptors of which >250
      are unique to nematodes. ODR-7 is the only member of this large divergent family
      whose functions have been defined genetically. ODR-7 is expressed in the AWA
      olfactory neurons and specifies AWA sensory identity by promoting the expression
      of AWA-specific signaling genes and repressing the expression of an AWC-specific
      olfactory receptor gene. To elucidate the molecular mechanisms of action of a
      divergent nuclear receptor, we have identified residues and domains required for
      different aspects of ODR-7 function in vivo. ODR-7 utilizes an unexpected
      diversity of mechanisms to regulate the expression of different sets of target
      genes. Moreover, these mechanisms are distinct in normal and heterologous
      cellular contexts. The odr-7 ortholog in the closely related nematode C. briggsae
      can fully substitute for all ODR-7-mediated functions, indicating conservation of
      function across 25-120 million years of divergence.

PMID- 14704166
TI  - The structure and early evolution of recently arisen gene duplicates in the
      Caenorhabditis elegans genome.
AB  - The significance of gene duplication in provisioning raw materials for the
      evolution of genomic diversity is widely recognized, but the early evolutionary
      dynamics of duplicate genes remain obscure. To elucidate the structural
      characteristics of newly arisen gene duplicates at infancy and their subsequent
      evolutionary properties, we analyzed gene pairs with < or =10% divergence at
      synonymous sites within the genome of Caenorhabditis elegans. Structural
      heterogeneity between duplicate copies is present very early in their
      evolutionary history and is maintained over longer evolutionary timescales,
      suggesting that duplications across gene boundaries in conjunction with shuffling
      events have at least as much potential to contribute to long-term evolution as do
      fully redundant (complete) duplicates. The median duplication span of 1.4 kb
      falls short of the average gene length in C. elegans (2.5 kb), suggesting that
      partial gene duplications are frequent. Most gene duplicates reside close to the
      parent copy at inception, often as tandem inverted loci, and appear to disperse
      in the genome as they age, as a result of reduced survivorship of duplicates
      located in proximity to the ancestral copy. We propose that illegitimate
      recombination events leading to inverted duplications play a disproportionately
      large role in gene duplication within this genome in comparison with other
      mechanisms.

PMID- 14704167
TI  - Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta
      independent and serotonin-dependent signaling pathway and likely functions both
      in the nervous system and in muscle.
AB  - egl-30 encodes the single C. elegans ortholog of vertebrate Galphaq family
      members. We analyzed the expression pattern of EGL-30 and found that it is
      broadly expressed, with highest expression in the nervous system and in
      pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as
      intragenic revertants of an egl-30 reduction-of-function mutation. Using these
      gain-of-function mutants and existing reduction-of-function mutants, we examined
      the site and mode of action of EGL-30. On the basis of pharmacological analysis,
      it has been determined that egl-30 functions both in the nervous system and in
      the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that
      eliminate detectable levels of serotonin reveals that egl-30 requires serotonin
      to regulate egg laying. Furthermore, pharmacological response assays strongly
      suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg
      laying. We also examined genetic interactions with mutations in the gene that
      encodes the single C. elegans homolog of PLCbeta and mutations in genes that
      encode signaling molecules downstream of PLCbeta. We conclude that PLCbeta
      functions in parallel with egl-30 with respect to egg laying or is not the major
      effector of EGL-30. In contrast, PLCbeta-mediated signaling is likely downstream
      of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that
      there are multiple signaling pathways downstream of EGL-30 and that different
      pathways could predominate with respect to the regulation of different behaviors.

PMID- 14704168
TI  - Characterization of a male-predominant antisense transcript underexpressed in
      hybrids of Drosophila pseudoobscura and D. persimilis.
AB  - Characterizing genes that are misregulated in hybrids may elucidate the genetic
      basis of hybrid sterility or other hybrid dysfunctions that contribute to
      speciation. Previously, a small segment of a male-predominant transcript that is
      underexpressed in adult male hybrids of Drosophila pseudoobscura and D.
      persimilis relative to pure species was identified in a differential display
      screen. Here, we obtained the full sequence of this 1330-bp transcript and
      determined that it is an antisense message with high sequence similarity to the
      D. melanogaster TRAP100 gene, part of the Mediator protein complex that regulates
      transcriptional initiation during development. Both the sense and the antisense
      messages are transcribed in D. pseudoobscura, but only the sense message
      (TRAP100) is transcribed in D. melanogaster complex species. Unlike the antisense
      message, the sense message is transcribed similarly in D. pseudoobscura males and
      females and in hybrids of D. pseudoobscura and D. persimilis. The high sequence
      similarity between distantly related species suggests that the sense message is
      functionally constrained within the genus. We speculate that the antisense
      transcript may have evolved a role in male-specific post-transcriptional
      regulation of TRAP100 in the D. pseudoobscura lineage and that its
      underexpression in sterile hybrid males may cause an overproduction of TRAP100
      protein, possibly yielding deleterious effects.

PMID- 14704169
TI  - The homologous chromosome is an effective template for the repair of mitotic DNA
      double-strand breaks in Drosophila.
AB  - In recombinational DNA double-strand break repair a homologous template for gene
      conversion may be located at several different genomic positions: on the
      homologous chromosome in diploid organisms, on the sister chromatid after DNA
      replication, or at an ectopic position. The use of the homologous chromosome in
      mitotic gene conversion is thought to be limited in the yeast Saccharomyces
      cerevisiae and mammalian cells. In contrast, by studying the repair of double
      strand breaks generated by the I-SceI rare-cutting endonuclease, we find that the
      homologous chromosome is frequently used in Drosophila melanogaster, which we
      suggest is attributable to somatic pairing of homologous chromosomes in mitotic
      cells of Drosophila. We also find that Drosophila mitotic cells of the germ line,
      like yeast, employ the homologous recombinational repair pathway more often than
      imperfect nonhomologous end joining.

PMID- 14704170
TI  - Selective constraints on intron evolution in Drosophila.
AB  - Intron sizes show an asymmetrical distribution in a number of organisms, with a
      large number of "short" introns clustered around a minimal intron length and a
      much broader distribution of longer introns. In Drosophila melanogaster, the
      short intron class is centered around 61 bp. The narrow length distribution
      suggests that natural selection may play a role in maintaining intron size. A
      comparison of 15 orthologous introns among species of the D. melanogaster
      subgroup indicates that, in general, short introns are not under greater DNA
      sequence or length constraints than long introns. There is a bias toward
      deletions in all introns (deletion/insertion ratio is 1.66), and the vast
      majority of indels are of short length (<10 bp). Indels occurring on the internal
      branches of the phylogenetic tree are significantly longer than those occurring
      on the terminal branches. These results are consistent with a compensatory model
      of intron length evolution in which slightly deleterious short deletions are
      frequently fixed within species by genetic drift, and relatively rare larger
      insertions that restore intron length are fixed by positive selection. A
      comparison of paralogous introns shared among duplicated genes suggests that
      length constraints differ between introns within the same gene. The janusA,
      janusB, and ocnus genes share two short introns derived from a common ancestor.
      The first of these introns shows significantly fewer indels than the second
      intron, although the two introns show a comparable number of substitutions. This
      indicates that intron-specific selective constraints have been maintained
      following gene duplication, which preceded the divergence of the D. melanogaster
      species subgroup.

PMID- 14704171
TI  - Alternative genetic foundations for a key social polymorphism in fire ants.
AB  - Little is known about the genetic foundations of colony social organization. One
      rare example in which a single major gene is implicated in the expression of
      alternative social organizations involves the presumed odorant-binding protein
      gene Gp-9 in fire ants. Specific amino acid substitutions in this gene invariably
      are associated with the expression of monogyny (single queen per colony) or
      polygyny (multiple queens per colony) in fire ant species of the Solenopsis
      richteri clade. These substitutions are hypothesized to alter the abilities of
      workers to recognize queens and thereby regulate their numbers in a colony. We
      examined whether these same substitutions underlie the monogyny/polygyny social
      polymorphism in the distantly related fire ant S. geminata. We found that Gp-9
      coding region sequences are identical in the polygyne and monogyne forms of this
      species, disproving our hypothesis that one or a few specific amino acid
      replacements in the protein are necessary to induce transitions in social
      organization in fire ants. On the other hand, polygyne S. geminata differs
      genetically from the monogyne form in ways not mirrored in the two forms of S.
      invicta, a well-studied member of the S. richteri clade, supporting the
      conclusion that polygyny did not evolve via analogous routes in the two lineages.
      Specifically, polygyne S. geminata has lower genetic diversity and different gene
      frequencies than the monogyne form, suggesting that the polygyne form originated
      via a founder event from a local monogyne population. These comparative data
      suggest an alternative route to polygyny in S. geminata in which loss of allelic
      variation at genes encoding recognition cues has led to a breakdown in
      discrimination abilities and the consequent acceptance of multiple queens in
      colonies.

PMID- 14704172
TI  - The pineapple eye gene is required for survival of Drosophila imaginal disc
      cells.
AB  - Each ommatidium of the Drosophila eye is constructed by precisely 19 specified
      precursor cells, generated in part during a second mitotic wave of cell divisions
      that overlaps early stages of ommatidial cell specification. Homozygotes for the
      pineapple eye mutation lack sufficient precursor cells due to apoptosis during
      the period of fate specification. In addition development is delayed by apoptosis
      during earlier imaginal disc growth. Null alleles are recessive lethal and
      allelic to l(2)31Ek; heteroallelic combinations can show developmental delay,
      abnormal eye development, and reduced fertility. Mosaic clones autonomously show
      extensive cell death. The pineapple eye gene was identified and predicted to
      encode a novel 582-amino-acid protein. The protein contains a novel, cysteine
      rich domain of 270 amino acids also found in predicted proteins of unknown
      function from other animals.

PMID- 14704173
TI  - Germline cell death is inhibited by P-element insertions disrupting the dcp
      1/pita nested gene pair in Drosophila.
AB  - Germline cell death in Drosophila oogenesis is controlled by distinct signals.
      The death of nurse cells in late oogenesis is developmentally regulated, whereas
      the death of egg chambers during mid-oogenesis is induced by environmental stress
      or developmental abnormalities. P-element insertions in the caspase gene dcp-1
      disrupt both dcp-1 and the outlying gene, pita, leading to lethality and
      defective nurse cell death in late oogenesis. By isolating single mutations in
      the two genes, we have found that the loss of both genes contributes to this
      ovary phenotype. Mutants of pita, which encodes a C2H2 zinc-finger protein, are
      homozygous lethal and show dumpless egg chambers and premature nurse cell death
      in germline clones. Early nurse cell death is not observed in the dcp-1/pita
      double mutants, suggesting that dcp-1+ activity is required for the mid-oogenesis
      cell death seen in pita mutants. dcp-1 mutants are viable and nurse cell death in
      late oogenesis occurs normally. However, starvation-induced germline cell death
      during mid-oogenesis is blocked, leading to a reduction and inappropriate nuclear
      localization of the active caspase Drice. These findings suggest that the
      combinatorial loss of pita and dcp-1 leads to the increased survival of abnormal
      egg chambers in mutants bearing the P-element alleles and that dcp-1 is essential
      for cell death during mid-oogenesis.

PMID- 14704174
TI  - l(3)malignant brain tumor and three novel genes are required for Drosophila germ
      cell formation.
AB  - To identify genes involved in the process of germ-cell formation in Drosophila, a
      maternal-effect screen using the FLP/FRT-ovoD method was performed on chromosome
      3R. In addition to expected mutations in the germ-cell determinant oskar and in
      other genes known to be involved in the process, several novel mutations caused
      defects in germ-cell formation. Mutations in any of three genes [l(3)malignant
      brain tumor, shackleton, and out of sync] affect the synchronous mitotic
      divisions and nuclear migration of the early embryo. The defects in nuclear
      migration or mitotic synchrony result in a reduction in germ-cell formation.
      Mutations in another gene identified in this screen, bebra, do not cause mitotic
      defects, but appear to act upstream of the localization of oskar. Analysis of our
      mutants demonstrates that two unique and independent processes must occur to form
      germ cells-germ-plasm formation and nuclear division/migration.

PMID- 14704175
TI  - Nucleotide variation of the Est-6 gene region in natural populations of
      Drosophila melanogaster.
AB  - We have investigated nucleotide polymorphism in the Est-6 gene region in four
      samples of Drosophila melanogaster derived from natural populations of East
      Africa (Zimbabwe), Europe (Spain), North America (California), and South America
      (Venezuela). There are two divergent sequence types in the North and South
      American samples, which are not perfectly (North America) or not at all (South
      America) associated with the Est-6 allozyme variation. Less pronounced or no
      sequence dimorphism occurs in the European and African samples, respectively. The
      level of nucleotide diversity is highest in the African sample, lower (and
      similar to each other) in the samples from Europe and North America, and lowest
      in the sample from South America. The extent of linkage disequilibrium is low in
      Africa (1.23% significant associations), but much higher in non-African
      populations (22.59, 21.45, and 37.68% in Europe, North America, and South
      America, respectively). Tests of neutrality with recombination are significant in
      non-African samples but not significant in the African sample. We propose that
      demographic history (bottleneck and admixture of genetically different
      populations) is the major factor shaping the nucleotide patterns in the Est-6
      gene region. However, positive selection modifies the pattern: balanced selection
      creates elevated levels of nucleotide variation around functionally important
      (target) polymorphic sites (RsaI-/RsaI+ in the promoter region and F/S in the
      coding region) in both African and non-African samples; and directional
      selection, acting during the geographic expansion phase of D. melanogaster,
      creates an excess of very similar sequences (RsaI- and S allelic lineages, in the
      promoter and coding regions, respectively) in the non-African samples.

PMID- 14704176
TI  - Hedgehog signaling in the Drosophila eye and head: an analysis of the effects of
      different patched trans-heterozygotes.
AB  - Characterization of different alleles of the Hedgehog receptor patched (ptc)
      indicates that they can be grouped into several classes. Most mutations result in
      complete loss of Ptc function. However, missense mutations located within the
      putative sterol-sensing domain (SSD) or C terminus of ptc encode antimorphic
      proteins that are unable to repress Smo activity and inhibit wild-type Ptc from
      doing so, but retain the ability to bind and sequester Hh. Analysis of the eye
      and head phenotypes of Drosophila melanogaster in various ptc/ptc(tuf1)
      heteroallelic combinations shows that these two classes of ptc allele can be
      easily distinguished by their eye phenotype, but not by their head phenotype.
      Adult eye size is inversely correlated with head vertex size, suggesting an
      alteration of cell fate within the eye-antennal disc. A balance between excess
      cell division and cell death in the mutant eye discs may also contribute to final
      eye size. In addition, contrary to results reported recently, the role of Hh
      signaling in the Drosophila head vertex appears to be primarily in patterning
      rather than in proliferation, with Ptc and Smo having opposing effects on
      formation of medial structures.

PMID- 14704177
TI  - The Drosophila melanogaster DNA Ligase IV gene plays a crucial role in the repair
      of radiation-induced DNA double-strand breaks and acts synergistically with
      Rad54.
AB  - DNA Ligase IV has a crucial role in double-strand break (DSB) repair through
      nonhomologous end joining (NHEJ). Most notably, its inactivation leads to
      embryonic lethality in mammals. To elucidate the role of DNA Ligase IV (Lig4) in
      DSB repair in a multicellular lower eukaryote, we generated viable Lig4-deficient
      Drosophila strains by P-element-mediated mutagenesis. Embryos and larvae of
      mutant lines are hypersensitive to ionizing radiation but hardly so to methyl
      methanesulfonate (MMS) or the crosslinking agent cis-diamminedichloroplatinum
      (cisDDP). To determine the relative contribution of NHEJ and homologous
      recombination (HR) in Drosophila, Lig4; Rad54 double-mutant flies were generated.
      Survival studies demonstrated that both HR and NHEJ have a major role in DSB
      repair. The synergistic increase in sensitivity seen in the double mutant, in
      comparison with both single mutants, indicates that both pathways partially
      overlap. However, during the very first hours after fertilization NHEJ has a
      minor role in DSB repair after exposure to ionizing radiation. Throughout the
      first stages of embryogenesis of the fly, HR is the predominant pathway in DSB
      repair. At late stages of development NHEJ also becomes less important. The
      residual survival of double mutants after irradiation strongly suggests the
      existence of a third pathway for the repair of DSBs in Drosophila.

PMID- 14704178
TI  - The Drosophila melanogaster importin alpha3 locus encodes an essential gene
      required for the development of both larval and adult tissues.
AB  - The nuclear transport of classical nuclear localization signal (cNLS)-containing
      proteins is mediated by the cNLS receptor importin alpha. The conventional
      importin alpha gene family in metazoan animals is composed of three clades that
      are conserved between flies and mammals and are referred to here as alpha1,
      alpha2, and alpha3. In contrast, plants and fungi contain only alpha1 genes. In
      this study we report that Drosophila importin alpha3 is required for the
      development of both larval and adult tissues. Importin alpha3 mutant flies die
      around the transition from first to second instar larvae, and homozygous importin
      alpha3 mutant eyes are defective. The transition to second instar larvae was
      rescued with importin alpha1, alpha2, or alpha3 transgenes, indicating that
      Importin alpha3 is normally required at this stage for an activity shared by all
      three importin alpha's. In contrast, an alpha3-specific biochemical activity(s)
      of Importin alpha3 is probably required for development to adults and
      photoreceptor cell development, since only an importin alpha3 transgene rescued
      these processes. These results are consistent with the view that the importin
      alpha's have both overlapping and distinct functions and that their role in
      animal development involves the spatial and temporal control of their expression.

PMID- 14704180
TI  - Screens for piwi suppressors in Drosophila identify dosage-dependent regulators
      of germline stem cell division.
AB  - The Drosophila piwi gene is the founding member of the only known family of genes
      whose function in stem cell maintenance is highly conserved in both animal and
      plant kingdoms. piwi mutants fail to maintain germline stem cells in both male
      and female gonads. The identification of piwi-interacting genes is essential for
      understanding how stem cell divisions are regulated by piwi-mediated mechanisms.
      To search for such genes, we screened the Drosophila third chromosome (
      approximately 36% of the euchromatic genome) for suppressor mutations of piwi2
      and identified six strong and three weak piwi suppressor genes/sequences. These
      genes/sequences interact negatively with piwi in a dosage-sensitive manner. Two
      of the strong suppressors represent known genes--serendipity-delta and similar,
      both encoding transcription factors. These findings reveal that the genetic
      regulation of germline stem cell division involves dosage-sensitive mechanisms
      and that such mechanisms exist at the transcriptional level. In addition, we
      identified three other types of piwi interactors. The first type consists of
      deficiencies that dominantly interact with piwi2 to cause male sterility,
      implying that dosage-sensitive regulation also exists in the male germline. The
      other two types are deficiencies that cause lethality and female-specific
      lethality in a piwi2 mutant background, revealing the zygotic function of piwi in
      somatic development.

PMID- 14704179
TI  - Influence of two Wolbachia strains on population structure of East African
      Drosophila simulans.
AB  - Drosophila simulans is hypothesized to have originated in continental East Africa
      or Madagascar. In this study, we investigated evolutionary forces operating on
      mitochondrial DNA (mtDNA) in populations of D. simulans from Zimbabwe, Malawi,
      Tanzania, and Kenya. Variation in mtDNA may be affected by positive selection,
      background selection, demographic history, and/or any maternally inherited factor
      such as the bacterial symbiont Wolbachia. In East Africa, the wRi and wMa
      Wolbachia strains associate with the siII or siIII mitochondrial haplogroups,
      respectively. To ask how polymorphism relates to Wolbachia infection status, we
      sequenced 1776 bp of mitochondrial DNA and 1029 bp of the X-linked per locus from
      79 lines. The two southern populations were infected with wRi and exhibited
      significantly reduced mtDNA variation, while Wolbachia-uninfected siII flies from
      Tanzania and Kenya showed high levels of mtDNA polymorphism. These are the first
      known populations of D. simulans that do not exhibit reduced mtDNA variation. We
      observed no mitochondrial variation in the siIII haplogroup regardless of
      Wolbachia infection status, suggesting positive or background selection. These
      populations offer a unique opportunity to monitor evolutionary dynamics in
      ancestral populations that harbor multiple strains of Wolbachia.

PMID- 14704181
TI  - The novel plant homeodomain protein rhinoceros antagonizes Ras signaling in the
      Drosophila eye.
AB  - The sequential specification of cell fates in the Drosophila eye requires
      repeated activation of the epidermal growth factor receptor (EGFR)/Ras/MAP kinase
      (MAPK) pathway. Equally important are the multiple layers of inhibitory
      regulation that prevent excessive or inappropriate signaling. Here we describe
      the molecular and genetic analysis of a previously uncharacterized gene,
      rhinoceros (rno), that we propose functions to restrict EGFR signaling in the
      eye. Loss of rno results in the overproduction of photoreceptors, cone cells, and
      pigment cells and a corresponding reduction in programmed cell death, all
      phenotypes characteristic of hyperactivated EGFR signaling. Genetic interactions
      between rno and multiple EGFR pathway components support this hypothesis. rno
      encodes a novel but evolutionarily conserved nuclear protein with a PHD zinc
      finger domain, a motif commonly found in chromatin-remodeling factors. Future
      analyses of rno will help to elucidate the regulatory strategies that modulate
      EGFR signaling in the fly eye.

PMID- 14704182
TI  - Recruitment of the proneural gene scute to the Drosophila sex-determination
      pathway.
AB  - In flies, scute (sc) works with its paralogs in the achaete-scute-complex (ASC)
      to direct neuronal development. However, in the family Drosophilidae, sc also
      acquired a role in the primary event of sex determination, X chromosome counting,
      by becoming an X chromosome signal element (XSE)-an evolutionary step shown here
      to have occurred after sc diverged from its closest paralog, achaete (ac). Two
      temperature-sensitive alleles, sc(sisB2) and sc(sisB3), which disrupt only sex
      determination, were recovered in a powerful F1 genetic selection and used to
      investigate how sc was recruited to the sex-determination pathway. sc(sisB2)
      revealed 3' nontranscribed regulatory sequences likely to be involved. The
      sc(sisB2) lesion abolished XSE activity when combined with mutations engineered
      in a sequence upstream of all XSEs. In contrast, changes in Sc protein sequence
      seem not to have been important for recruitment. The observation that the other
      new allele, sc(sisB3), eliminates the C-terminal half of Sc without affecting
      neurogenesis and that sc(sisB1), the most XSE-specific allele previously
      available, is a nonsense mutant, would seem to suggest the opposite, but we show
      that housefly Sc can substitute for fruit fly Sc in sex determination, despite
      lacking Drosophilidae-specific conserved residues in its C-terminal half. Lack of
      synergistic lethality among mutations in sc, twist, and dorsal argue against a
      proposed role for sc in mesoderm formation that had seemed potentially relevant
      to sex-pathway recruitment. The screen that yielded new sc alleles also generated
      autosomal duplications that argue against the textbook view that fruit fly sex
      signal evolution recruited a set of autosomal signal elements comparable to the
      XSEs.

PMID- 14704183
TI  - Wolbachia and cytoplasmic incompatibility in the California Culex pipiens
      mosquito species complex: parameter estimates and infection dynamics in natural
      populations.
AB  - Before maternally inherited bacterial symbionts like Wolbachia, which cause
      cytoplasmic incompatibility (CI; reduced hatch rate) when infected males mate
      with uninfected females, can be used in a program to control vector-borne
      diseases it is essential to understand their dynamics of infection in natural
      arthropod vector populations. Our study had four goals: (1) quantify the number
      of Wolbachia strains circulating in the California Culex pipiens species complex,
      (2) investigate Wolbachia infection frequencies and distribution in natural
      California populations, (3) estimate the parameters that govern Wolbachia spread
      among Cx. pipiens under laboratory and field conditions, and (4) use these values
      to estimate equilibrium levels and compare predicted infection prevalence levels
      to those observed in nature. Strain-specific PCR, wsp gene sequencing, and
      crossing experiments indicated that a single Wolbachia strain infects Californian
      Cx. pipiens. Infection frequency was near or at fixation in all populations
      sampled for 2 years along a >1000-km north-south transect. The combined statewide
      infection frequency was 99.4%. Incompatible crosses were 100% sterile under
      laboratory and field conditions. Sterility decreased negligibly with male age in
      the laboratory. Infection had no significant effect on female fecundity under
      laboratory or field conditions. Vertical transmission was >99% in the laboratory
      and approximately 98.6% in the field. Using field data, models predicted that
      Wolbachia will spread to fixation if infection exceeds an unstable equilibrium
      point above 1.4%. Our estimates accurately predicted infection frequencies in
      natural populations. If certain technical hurdles can be overcome, our data
      indicate that Wolbachia can invade vector populations as part of an applied
      transgenic strategy for vector-borne disease reduction.

PMID- 14704184
TI  - Genetics of P-element transposition into Drosophila melanogaster centric
      heterochromatin.
AB  - Heterochromatin is a major component of higher eukaryotic genomes, but progress
      in understanding the molecular structure and composition of heterochromatin has
      lagged behind the production of relatively complete euchromatic genome sequences.
      The introduction of single-copy molecular-genetic entry points can greatly
      facilitate structure and sequence analysis of heterochromatic regions that are
      rich in repeated DNA. In this study, we report the isolation of 502 new P-element
      insertions into Drosophila melanogaster centric heterochromatin, generated in
      nine different genetic screens that relied on mosaic silencing (position-effect
      variegation, or PEV) of the yellow gene present in the transposon. The highest
      frequencies of recovery of variegating insertions were observed when centric
      insertions were used as the source for mobilization. We propose that the
      increased recovery of variegating insertions from heterochromatic starting sites
      may result from the physical proximity of different heterochromatic regions in
      germline nuclei or from the association of mobilizing elements with
      heterochromatin proteins. High frequencies of variegating insertions were also
      recovered when a potent suppressor of PEV (an extra Y chromosome) was present in
      both the mobilization and selection generations, presumably due to the effects of
      chromatin structure on P-element mobilization, insertion, and phenotypic
      selection. Finally, fewer variegating insertions were recovered after
      mobilization in females, in comparison to males, which may reflect differences in
      heterochromatin structure in the female and male germlines. FISH localization of
      a subset of the insertions confirmed that 98% of the variegating lines contain
      heterochromatic insertions and that these schemes produce a broader distribution
      of insertion sites. The results of these schemes have identified the most
      efficient methods for generating centric heterochromatin P insertions. In
      addition, the large collection of insertions produced by these screens provides
      molecular-genetic entry points for mapping, sequencing, and functional analysis
      of Drosophila heterochromatin.

PMID- 14704185
TI  - Age-associated activation of epigenetically repressed genes in the mouse.
AB  - Epigenetic control of gene expression is a consistent feature of differentiated
      mammalian cell types. Epigenetic expression patterns are mitotically heritable
      and are stably maintained in adult cells. However, unlike somatic DNA mutation,
      little is known about the occurrence of epigenetic change, or epimutation, during
      normal adult life. We have monitored the age-associated maintenance of two
      epigenetic systems--X inactivation and genomic imprinting--using the genes Atp7a
      and Igf2, respectively. Quantitative measurements of RNA transcripts from the
      inactive and active alleles were performed in mice from 2 to 24 months of age.
      For both genes, older animal cohorts showed reproducible increases in transcripts
      expressed from the silenced alleles. Loss of X chromosome silencing showed cohort
      mean increases of up to 2.2%, while imprinted-gene activation increased up to
      6.7%. The results support the hypothesis that epigenetic loss of gene repression
      occurs in normal tissues and may be a contributing factor in progressive
      physiological dysfunction seen during mammalian aging. Quantitatively, the loss
      of epigenetic control may be one to two orders of magnitude greater than
      previously determined somatic DNA mutation.

PMID- 14704186
TI  - Evolution of the human ASPM gene, a major determinant of brain size.
AB  - The size of human brain tripled over a period of approximately 2 million years
      (MY) that ended 0.2-0.4 MY ago. This evolutionary expansion is believed to be
      important to the emergence of human language and other high-order cognitive
      functions, yet its genetic basis remains unknown. An evolutionary analysis of
      genes controlling brain development may shed light on it. ASPM (abnormal spindle
      like microcephaly associated) is one of such genes, as nonsense mutations lead to
      primary microcephaly, a human disease characterized by a 70% reduction in brain
      size. Here I provide evidence suggesting that human ASPM went through an episode
      of accelerated sequence evolution by positive Darwinian selection after the split
      of humans and chimpanzees but before the separation of modern non-Africans from
      Africans. Because positive selection acts on a gene only when the gene function
      is altered and the organismal fitness is increased, my results suggest that
      adaptive functional modifications occurred in human ASPM and that it may be a
      major genetic component underlying the evolution of the human brain.

PMID- 14704187
TI  - Sequences associated with human iris pigmentation.
AB  - To determine whether and how common polymorphisms are associated with natural
      distributions of iris colors, we surveyed 851 individuals of mainly European
      descent at 335 SNP loci in 13 pigmentation genes and 419 other SNPs distributed
      throughout the genome and known or thought to be informative for certain elements
      of population structure. We identified numerous SNPs, haplotypes, and diplotypes
      (diploid pairs of haplotypes) within the OCA2, MYO5A, TYRP1, AIM, DCT, and TYR
      genes and the CYP1A2-15q22-ter, CYP1B1-2p21, CYP2C8-10q23, CYP2C9-10q24, and MAOA
      Xp11.4 regions as significantly associated with iris colors. Half of the
      associated SNPs were located on chromosome 15, which corresponds with results
      that others have previously obtained from linkage analysis. We identified 5
      additional genes (ASIP, MC1R, POMC, and SILV) and one additional region (GSTT2
      22q11.23) with haplotype and/or diplotypes, but not individual SNP alleles
      associated with iris colors. For most of the genes, multilocus gene-wise genotype
      sequences were more strongly associated with iris colors than were haplotypes or
      SNP alleles. Diplotypes for these genes explain 15% of iris color variation.
      Apart from representing the first comprehensive candidate gene study for variable
      iris pigmentation and constituting a first step toward developing a
      classification model for the inference of iris color from DNA, our results
      suggest that cryptic population structure might serve as a leverage tool for
      complex trait gene mapping if genomes are screened with the appropriate ancestry
      informative markers.

PMID- 14704188
TI  - Detection of new quantitative trait Loci for susceptibility to transmissible
      spongiform encephalopathies in mice.
AB  - Susceptibility to scrapie is largely controlled by the PRNP gene in mice and in
      several other species. However, individuals with identical scrapie susceptibility
      Prnp alleles may have very different incubation periods, suggesting the influence
      of other environmental and genetic factors. To detect loci influencing
      susceptibility to TSE, two mouse lines carrying the same PRNP genotype (C57BL and
      RIII) were crossed to produce an F2 population inoculated intracerebrally with a
      mouse-adapted scrapie strain. Linkage was studied between 72 markers and the age
      of death of F2 animals. Six QTL were detected, two at a genome-wide significant
      level (chromosomes 5 and 7) and four at a genome-wide suggestive level
      (chromosomes 4, 6, 8, and 17). Our results confirmed the existence of some QTL
      that were detected previously (chromosomes 4, 6, 7, and 8) while others were
      found only in the present study (chromosomes 5 and 17). Furthermore, it seems
      that some QTL (chromosomes 4 and 8) are involved in resistance to scrapie as well
      as to BSE.

PMID- 14704189
TI  - Expression of the Arabidopsis transposable element Tag1 is targeted to developing
      gametophytes.
AB  - The Arabidopsis transposon Tag1 undergoes late excision during vegetative and
      germinal development in plants containing 35S-Tag1-GUS constructs. To determine
      if transcriptional regulation can account for the developmental control of Tag1
      excision, the transcriptional activity of Tag1 promoter-GUS fusion constructs of
      various lengths was examined in transgenic plants. All constructs showed
      expression in the reproductive organs of developing flowers but no expression in
      leaves. Expression was restricted to developing gametophytes in both male and
      female lineages. Quantitative RT-PCR analysis confirmed that Tag1 expression
      predominates in the reproductive organs of flower buds. These results are
      consistent with late germinal excision of Tag1, but they cannot explain the
      vegetative excision activity of Tag1 observed with 35S-Tag1-GUS constructs. To
      resolve this issue, Tag1 excision was reexamined using elements with no adjacent
      35S promoter sequences. Tag1 excision in this context is restricted to germinal
      events with no detectable vegetative excision. If a 35S enhancer sequence is
      placed next to Tag1, vegetative excision is restored. These results indicate that
      the intrinsic activity of Tag1 is restricted to germinal excision due to targeted
      expression of the Tag1 transposase to developing gametophytes and that this
      activity is altered by the presence of adjacent enhancers or promoters.

PMID- 14704190
TI  - Toward a marker-dense meiotic map of the potato genome: lessons from linkage
      group I.
AB  - Segregation data were obtained for 1260 potato linkage group I-specific AFLP loci
      from a heterozygous diploid potato population. Analytical tools that identified
      potential typing errors and/or inconsistencies in the data and that assembled
      cosegregating markers into bins were applied. Bins contain multiple-marker data
      sets with an identical segregation pattern, which is defined as the bin
      signature. The bin signatures were used to construct a skeleton bin map that was
      based solely on observed recombination events. Markers that did not match any of
      the bin signatures exactly (and that were excluded from the calculation of the
      skeleton bin map) were placed on the map by maximum likelihood. The resulting
      maternal and paternal maps consisted of 95 and 101 bins, respectively. Markers
      derived from EcoRI/MseI, PstI/MseI, and SacI/MseI primer combinations showed
      different genetic distributions. Approximately three-fourths of the markers
      placed into a bin were considered to fit well on the basis of an estimated
      residual "error rate" of 0-3%. However, twice as many PstI-based markers fit
      badly, suggesting that parental PstI-site methylation patterns had changed in the
      population. Recombination frequencies were highly variable across the map. Inert,
      presumably centromeric, regions caused extensive marker clustering while
      recombination hotspots (or regions identical by descent) resulted in empty bins,
      despite the level of marker saturation.

PMID- 14704191
TI  - Genetic structure and diversity among maize inbred lines as inferred from DNA
      microsatellites.
AB  - Two hundred and sixty maize inbred lines, representative of the genetic diversity
      among essentially all public lines of importance to temperate breeding and many
      important tropical and subtropical lines, were assayed for polymorphism at 94
      microsatellite loci. The 2039 alleles identified served as raw data for
      estimating genetic structure and diversity. A model-based clustering analysis
      placed the inbred lines in five clusters that correspond to major breeding groups
      plus a set of lines showing evidence of mixed origins. A "phylogenetic" tree was
      constructed to further assess the genetic structure of maize inbreds, showing
      good agreement with the pedigree information and the cluster analysis. Tropical
      and subtropical inbreds possess a greater number of alleles and greater gene
      diversity than their temperate counterparts. The temperate Stiff Stalk lines are
      on average the most divergent from all other inbred groups. Comparison of
      diversity in equivalent samples of inbreds and open-pollinated landraces revealed
      that maize inbreds capture <80% of the alleles in the landraces, suggesting that
      landraces can provide additional genetic diversity for maize breeding. The
      contributions of four different segments of the landrace gene pool to each inbred
      group's gene pool were estimated using a novel likelihood-based model. The
      estimates are largely consistent with known histories of the inbreds and indicate
      that tropical highland germplasm is poorly represented in maize inbreds. Core
      sets of inbreds that capture maximal allelic richness were defined. These or
      similar core sets can be used for a variety of genetic applications in maize.

PMID- 14704192
TI  - Detailed mapping of the species cytoplasm-specific (scs) gene in durum wheat.
AB  - The compatibility-inducing action of the scs(ti) (species cytoplasm-specific gene
      derived from Triticum timopheevii) and Vi (vitality) genes can be observed when a
      durum (T. turgidum) nucleus is placed in T. longissimum cytoplasm. These two
      genes restore compatibility between an otherwise incompatible nucleus and
      cytoplasm. The objective of this study was to localize the scs(ti) gene on a
      linkage map of chromosome 1A, which could eventually be used to clone the gene.
      The mapping population consisted of 110 F2 individuals derived from crossing a
      Langdon-T. dicoccoides chromosome 1A substitution line with a euplasmic (normal
      cytoplasm) line homozygous for the scs(ti) gene. Through a series of testcrosses
      the genotypes of the 110 individuals were determined: 22 had two copies, 59 had
      one copy, and 29 had no copy of the scs(ti) gene. Data from RFLP, AFLP, and
      microsatellite analysis were used to create a linkage map. The flanking marker
      loci found for the scs(ti) gene were Xbcd12 and Xbcd1449-1A.2 with distances of
      2.3 and 0.6 cM, respectively. Nearly 10% of individuals in this population were
      double recombinant for a genetic interval of <3 cM. A blistering phenotype
      reminiscent of the phenotype observed in maize brittle-1 mutable was also evident
      in these individuals. The higher frequency of double recombination within this
      region and seed-blistering phenotype could be an indication of a transposable
      element(s) in this locus.

PMID- 14704193
TI  - Maize ROP2 GTPase provides a competitive advantage to the male gametophyte.
AB  - Rop GTPases have been implicated in the regulation of plant signal transduction
      and cell morphogenesis. To explore ROP2 function in maize, we isolated five
      Mutator transposon insertions (rop2::Mu alleles). Transmission frequency through
      the male gametophyte, but not the female, was lower than expected in three of the
      rop2::Mu mutants. These three alleles formed an allelic series on the basis of
      the relative transmission rate of each when crossed as trans-heterozygotes. A
      dramatic reduction in the level of ROP2-mRNA in pollen was associated with the
      three alleles causing a transmission defect, whereas a rop2::Mu allele that did
      not result in a defect had wild-type transcript levels, thus confirming that
      mutation of rop2 causes the mutant phenotype. These data strongly support a role
      for rop2 in male gametophyte function, perhaps surprisingly, given the expression
      in pollen of the nearly identical duplicate gene rop9. However, the transmission
      defect was apparent only when a rop2::Mu heterozygote was used as the pollen
      donor or when a mixture of wild-type and homozygous mutant pollen was used. Thus,
      mutant pollen is at a competitive disadvantage compared to wild-type pollen,
      although mutant pollen grains lacked an obvious cellular defect. Our data
      demonstrate the importance in vivo of a specific Rop, rop2, in the male
      gametophyte.

PMID- 14704194
TI  - Selection and drift in subdivided populations: a straightforward method for
      deriving diffusion approximations and applications involving dominance, selfing
      and local extinctions.
AB  - Population structure affects the relative influence of selection and drift on the
      change in allele frequencies. Several models have been proposed recently, using
      diffusion approximations to calculate fixation probabilities, fixation times, and
      equilibrium properties of subdivided populations. We propose here a simple method
      to construct diffusion approximations in structured populations; it relies on
      general expressions for the expectation and variance in allele frequency change
      over one generation, in terms of partial derivatives of a "fitness function" and
      probabilities of genetic identity evaluated in a neutral model. In the limit of a
      very large number of demes, these probabilities can be expressed as functions of
      average allele frequencies in the metapopulation, provided that coalescence
      occurs on two different timescales, which is the case in the island model. We
      then use the method to derive expressions for the probability of fixation of new
      mutations, as a function of their dominance coefficient, the rate of partial
      selfing, and the rate of deme extinction. We obtain more precise approximations
      than those derived by recent work, in particular (but not only) when deme sizes
      are small. Comparisons with simulations show that the method gives good results
      as long as migration is stronger than selection.

PMID- 14704195
TI  - On the evolutionary advantage of fitness-associated recombination.
AB  - The adaptive value of recombination remains something of a puzzle. One of the
      basic problems is that recombination not only creates new and advantageous
      genetic combinations, but also breaks down existing good ones. A negative
      correlation between the fitness of an individual and its recombination rate would
      result in prolonged integrity of fitter genetic combinations while enabling less
      fit ones to produce new combinations. Such a correlation could be mediated by
      various factors, including stress responses, age, or direct DNA damage. For
      haploid population models, we show that an allele for such fitness-associated
      recombination (FAR) can spread both in asexual populations and in populations
      reproducing sexually at any uniform recombination rate. FAR also carries an
      advantage for the population as a whole, resulting in a higher average fitness at
      mutation-selection balance. These results are demonstrated in populations
      adapting to new environments as well as in well-adapted populations coping with
      deleterious mutations. Current experimental results providing evidence for the
      existence of FAR in nature are discussed.

PMID- 14704196
TI  - The genetics of adaptation: the roles of pleiotropy, stabilizing selection and
      drift in shaping the distribution of bidirectional fixed mutational effects.
AB  - Pleiotropy allows for the deterministic fixation of bidirectional mutations:
      mutations with effects both in the direction of selection and opposite to
      selection for the same character. Mutations with deleterious effects on some
      characters can fix because of beneficial effects on other characters. This study
      analytically quantifies the expected frequency of mutations that fix with
      negative and positive effects on a character and the average size of a fixed
      effect on a character when a mutation pleiotropically affects from very few to
      many characters. The analysis allows for mutational distributions that vary in
      shape and provides a framework that would allow for varying the frequency at
      which mutations arise with deleterious and positive effects on characters. The
      results show that a large fraction of fixed mutations will have deleterious
      pleiotropic effects even when mutation affects as little as two characters and
      only directional selection is occurring, and, not surprisingly, as the degree of
      pleiotropy increases the frequency of fixed deleterious effects increases. As a
      point of comparison, we show how stabilizing selection and random genetic drift
      affect the bidirectional distribution of fixed mutational effects. The results
      are then applied to QTL studies that seek to find loci that contribute to
      phenotypic differences between populations or species. It is shown that QTL
      studies are biased against detecting chromosome regions that have deleterious
      pleiotropic effects on characters.

PMID- 14704197
TI  - Patterns of inbreeding depression and architecture of the load in subdivided
      populations.
AB  - Inbreeding depression is a general phenomenon that is due mainly to recessive
      deleterious mutations, the so-called mutation load. It has been much studied
      theoretically. However, until very recently, population structure has not been
      taken into account, even though it can be an important factor in the evolution of
      populations. Population subdivision modifies the dynamics of deleterious
      mutations because the outcome of selection depends on processes both within
      populations (selection and drift) and between populations (migration). Here, we
      present a general model that permits us to gain insight into patterns of
      inbreeding depression, heterosis, and the load in subdivided populations. We show
      that they can be interpreted with reference to single-population theory, using an
      appropriate local effective population size that integrates the effects of drift,
      selection, and migration. We term this the "effective population size of
      selection" (NS(e)). For the infinite island model, for example, it is equal to
      NS(e) = N1 + m/hs, where N is the local population size, m the migration rate,
      and h and s the dominance and selection coefficients of deleterious mutation. Our
      results have implications for the estimation and interpretation of inbreeding
      depression in subdivided populations, especially regarding conservation issues.
      We also discuss the possible effects of migration and subdivision on the
      evolution of mating systems.

PMID- 14704198
TI  - Modeling linkage disequilibrium and identifying recombination hotspots using
      single-nucleotide polymorphism data.
AB  - We introduce a new statistical model for patterns of linkage disequilibrium (LD)
      among multiple SNPs in a population sample. The model overcomes limitations of
      existing approaches to understanding, summarizing, and interpreting LD by (i)
      relating patterns of LD directly to the underlying recombination process; (ii)
      considering all loci simultaneously, rather than pairwise; (iii) avoiding the
      assumption that LD necessarily has a "block-like" structure; and (iv) being
      computationally tractable for huge genomic regions (up to complete chromosomes).
      We examine in detail one natural application of the model: estimation of
      underlying recombination rates from population data. Using simulation, we show
      that in the case where recombination is assumed constant across the region of
      interest, recombination rate estimates based on our model are competitive with
      the very best of current available methods. More importantly, we demonstrate, on
      real and simulated data, the potential of the model to help identify and quantify
      fine-scale variation in recombination rate from population data. We also outline
      how the model could be useful in other contexts, such as in the development of
      more efficient haplotype-based methods for LD mapping.

PMID- 14704199
TI  - A graph-theoretic approach to comparing and integrating genetic, physical and
      sequence-based maps.
AB  - For many species, multiple maps are available, often constructed independently by
      different research groups using different sets of markers and different source
      material. Integration of these maps provides a higher density of markers and
      greater genome coverage than is possible using a single study. In this article,
      we describe a novel approach to comparing and integrating maps by using abstract
      graphs. A map is modeled as a directed graph in which nodes represent mapped
      markers and edges define the order of adjacent markers. Independently constructed
      graphs representing corresponding maps from different studies are merged on the
      basis of their common loci. Absence of a path between two nodes indicates that
      their order is undetermined. A cycle indicates inconsistency among the mapping
      studies with regard to the order of the loci involved. The integrated graph thus
      produced represents a complete picture of all of the mapping studies that
      comprise it, including all of the ambiguities and inconsistencies among them. The
      objective of this representation is to guide additional research aimed at
      interpreting these ambiguities and inconsistencies in locus order rather than
      presenting a "consensus order" that ignores these problems.

PMID- 14704200
TI  - Recombination can evolve in large finite populations given selection on
      sufficient loci.
AB  - It is well known that an allele causing increased recombination is expected to
      proliferate as a result of genetic drift in a finite population undergoing
      selection, without requiring other mechanisms. This is supported by recent
      simulations apparently demonstrating that, in small populations, drift is more
      important than epistasis in increasing recombination, with this effect
      disappearing in larger finite populations. However, recent experimental evidence
      finds a greater advantage for recombination in larger populations. These results
      are reconciled by demonstrating through simulation without epistasis that for m
      loci recombination has an appreciable selective advantage over a range of
      population sizes (am, bm). bm increases steadily with m while am remains fairly
      static. Thus, however large the finite population, if selection acts on
      sufficiently many loci, an allele that increases recombination is selected for.
      We show that as selection acts on our finite population, recombination increases
      the variance in expected log fitness, causing indirect selection on a
      recombination-modifying locus. This effect is enhanced in those populations with
      more loci because the variance in phenotypic fitnesses in relation to the
      possible range will be smaller. Thus fixation of a particular haplotype is less
      likely to occur, increasing the advantage of recombination.

PMID- 14704201
TI  - Theoretical basis of the Beavis effect.
AB  - The core of statistical inference is based on both hypothesis testing and
      estimation. The use of inferential statistics for QTL identification thus
      includes estimation of genetic effects and statistical tests. Typically, QTL are
      reported only when the test statistics reach a predetermined critical value.
      Therefore, the estimated effects of detected QTL are actually sampled from a
      truncated distribution. As a result, the expectations of detected QTL effects are
      biased upward. In a simulation study, William D. Beavis showed that the average
      estimates of phenotypic variances associated with correctly identified QTL were
      greatly overestimated if only 100 progeny were evaluated, slightly overestimated
      if 500 progeny were evaluated, and fairly close to the actual magnitude when 1000
      progeny were evaluated. This phenomenon has subsequently been called the Beavis
      effect. Understanding the theoretical basis of the Beavis effect will help
      interpret QTL mapping results and improve success of marker-assisted selection.
      This study provides a statistical explanation for the Beavis effect. The
      theoretical prediction agrees well with the observations reported in Beavis's
      original simulation study. Application of the theory to meta-analysis of QTL
      mapping is discussed.

PMID- 14704202
TI  - Constructing large-scale genetic maps using an evolutionary strategy algorithm.
AB  - This article is devoted to the problem of ordering in linkage groups with many
      dozens or even hundreds of markers. The ordering problem belongs to the field of
      discrete optimization on a set of all possible orders, amounting to n!/2 for n
      loci; hence it is considered an NP-hard problem. Several authors attempted to
      employ the methods developed in the well-known traveling salesman problem (TSP)
      for multilocus ordering, using the assumption that for a set of linked loci the
      true order will be the one that minimizes the total length of the linkage group.
      A novel, fast, and reliable algorithm developed for the TSP and based on
      evolution-strategy discrete optimization was applied in this study for multilocus
      ordering on the basis of pairwise recombination frequencies. The quality of
      derived maps under various complications (dominant vs. codominant markers, marker
      misclassification, negative and positive interference, and missing data) was
      analyzed using simulated data with approximately 50-400 markers. High performance
      of the employed algorithm allows systematic treatment of the problem of
      verification of the obtained multilocus orders on the basis of computing
      intensive bootstrap and/or jackknife approaches for detecting and removing
      questionable marker scores, thereby stabilizing the resulting maps. Parallel
      calculation technology can easily be adopted for further acceleration of the
      proposed algorithm. Real data analysis (on maize chromosome 1 with 230 markers)
      is provided to illustrate the proposed methodology.

PMID- 14704203
TI  - MLH1p and MLH3p localize to precociously induced chiasmata of okadaic-acid
      treated mouse spermatocytes.
AB  - With the phosphatase inhibitor, okadaic acid, we induce the precocious onset of
      the chiasmate stage and under those conditions show that the recombination
      nodules, MLH1 and MLH3 foci, are localized to the chiasmata. It is concluded that
      MLH1/3 foci are appropriate markers for the studies of crossovers/chiasmata
      development and distribution at late meiotic prophase.

PMID- 14704204
TI  - Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic
      crossing over but not for gene conversion.
AB  - Most models of homologous recombination invoke cleavage of Holliday junctions to
      explain crossing over. The Mus81.Eme1 endonuclease from fission yeast and humans
      cleaves Holliday junctions and other branched DNA structures, leaving its
      physiological substrate uncertain. We report here that Schizosaccharomyces pombe
      mus81 mutants have normal or elevated frequencies of gene conversion but 20- to
      100-fold reduced frequencies of crossing over. Thus, gene conversion and crossing
      over can be genetically separated, and Mus81 is required for crossing over,
      supporting the hypothesis that the fission yeast Mus81.Eme1 protein complex
      resolves Holliday junctions in meiotic cells.

PMID- 14704206
TI  - Double-stranded RNA interference of a rice PI/GLO paralog, OsMADS2, uncovers its
      second-whorl-specific function in floral organ patterning.
AB  - Unlike many eudicot species, grasses have duplicated PI/GLO-like genes.
      Functional analysis of one of the rice PI/GLO paralogs, OsMADS2, is reported
      here. Our data demonstrate its essential role in lodicule development and
      implicate the second PI/GLO paralog, OsMADS4, to suffice for stamen
      specification. We provide the first evidence for differential contributions of
      grass PI/GLO paralogs in patterning second- and third-whorl floral organs.

PMID- 14704205
TI  - A Sod2 null mutation confers severely reduced adult life span in Drosophila.
AB  - A null mutation for the Sod2 gene, Sod2n283, was obtained in Drosophila
      melanogaster. Homozygous Sod2 null (Sodn283/Sodn283) adult flies survive up to 24
      hr following eclosion, a phenotype reminiscent of mice, where Sod2-/- progeny
      suffer neonatal lethality. Sodn283/+ heterozygotes are sensitive to oxidative
      stress induced by paraquat treatment.

PMID- 14704207
TI  - Distinguishing the hitchhiking and background selection models.
AB  - A simple method to distinguish hitchhiking and background selection is proposed.
      It is based on the observation that these models make different predictions about
      the average level of nucleotide diversity in regions of low recombination. The
      method is applied to data from Drosophila melanogaster and two highly selfing
      tomato species.

PMID- 14704208
TI  - Random mating with a finite number of matings.
AB  - Random mating is the null model central to population genetics. One assumption
      behind random mating is that individuals mate an infinite number of times. This
      is obviously unrealistic. Here we show that when each female mates a finite
      number of times, the effective size of the population is substantially decreased.

PMID- 14704210
TI  - N170 or N1? Spatiotemporal differences between object and face processing using
      ERPs.
AB  - The ERP component N170 is face-sensitive, yet its specificity for faces is
      controversial. We recorded ERPs while subjects viewed upright and inverted faces
      and seven object categories. Peak, topography and segmentation analyses were
      performed. N170 was earlier and larger to faces than to all objects. The classic
      increase in amplitude and latency was found for inverted faces on N170 but also
      on P1. Segmentation analyses revealed an extra map found only for faces,
      reflecting an extra cluster of activity compared to objects. While the N1 for
      objects seems to reflect the return to baseline from the P1, the N170 for faces
      reflects a supplement activity. The electrophysiological 'specificity' of faces
      could lie in the involvement of extra generators for face processing compared to
      objects and the N170 for faces seems qualitatively different from the N1 for
      objects. Object and face processing also differed as early as 120 ms.

PMID- 14704209
TI  - The role of L1 in axon pathfinding and fasciculation.
AB  - The neural cell adhesion molecule L1 has been found to play important roles in
      axon growth and fasciculation. Our main objective was to determine the role of L1
      during the development of connections between thalamus and cortex. We find that
      thalamocortical and corticothalamic axons in mice lacking L1 are
      hyperfasciculated, a subset of thalamocortical axons make pathfinding errors and
      thalamocortical axon growth cones are abnormally long in the subplate. These
      defects occur despite formation of six cortical layers and formation of
      topographically appropriate thalamocortical connections. The loss of L1 is
      accompanied by loss of expression of ankyrin-B, an intracellular L1 binding
      partner, suggesting that L1 is involved in the regulation of Ank2 stability. We
      postulate that the pathfinding errors, growth cone abnormalities and
      hyperfasciculation of axons following loss of L1 reflect both a shift in binding
      partners among axons and different substrates and a loss of appropriate
      interactions with the cytoskeleton.

PMID- 14704211
TI  - Age-related changes in neural activity during visual target detection measured by
      fMRI.
AB  - We used functional magnetic resonance imaging (fMRI) of a visual target detection
      (oddball) task to investigate age differences in neural activation for the
      detection of two types of infrequent events: visually simple items requiring a
      response shift (targets) and visually complex items that did not entail a
      response shift (novels). Targets activated several prefrontal regions (e.g.
      middle frontal gyrus), as well as deep gray matter regions (caudate, putamen,
      thalamus and insula). Prefrontal activation was similar for younger and older
      adults, whereas deep gray matter activation was relatively greater for the older
      adults. Novels activated occipital regions (fusiform and lateral occipital gyri),
      and this activation was relatively reduced for older adults. The changes in
      behavioral performance across the task conditions were similar for the two age
      groups, although the older adults' responses were slower overall. Regression
      analyses of the relation between neural activation and task performance (response
      time) indicated that whereas performance was mediated most directly by prefrontal
      cortex for younger adults, older adults' performance was influenced to a greater
      extent by deep gray matter structures. Older adults may place relatively greater
      emphasis on the attentional control of response regulation, in compensation for
      the age-related decline in visual processing efficiency.

PMID- 14704212
TI  - Enlarged temporal lobes in Turner syndrome: an X-chromosome effect?
AB  - Gender differences in brain morphology have previously been reported in the
      temporal lobe and an 'X-chromosome dosage effect' has been described in Turner
      syndrome (45,X). To examine this further, we investigated temporal lobe
      morphology, metabolism and function in nine children with non-mosaic Turner
      syndrome using magnetic resonance imaging, (1)H magnetic resonance spectroscopy
      and neuropsychological testing and compared outcomes with results from nine age
      matched control girls (46,XX). Turner subjects were found to have significantly
      larger superior temporal lobes (P = 0.004) and middle temporal lobes (P = 0.047)
      than controls. The size of the temporal lobe was found to correlate negatively
      with temporal lobe choline-containing compounds suggesting that increased
      temporal lobe size is associated with larger cells and/or decreased dendrites.
      This suggests a developmental failure to prune neurons. The degree of enlargement
      correlates negatively with functional performance on temporal-lobe associated
      tasks, suggesting that the enlargement may be a compensatory mechanism, or
      possibly causative in the case of semantic fluency performance. These temporal
      lobe abnormalities are discussed with reference to genes which are absent in
      Turner syndrome and to hormonal differences between Turner syndrome subjects and
      46,XX controls.

PMID- 14704213
TI  - Linking hemodynamic and electrophysiological measures of brain activity: evidence
      from functional MRI and intracranial field potentials.
AB  - We investigated the relation between electrophysiological and hemodynamic
      measures of brain activity through comparison of intracranially recorded event
      related local field potentials (ERPs) and blood-oxygenation level dependent
      functional magnetic resonance imaging (BOLD fMRI). We manipulated the duration of
      visual checkerboard stimuli across trials and measured stimulus-duration-related
      changes in ERP and BOLD activity in three brain regions: peri-calcarine cortex,
      the fusiform gyrus and lateral temporal-occipital (LTO) cortex. ERPs were
      recorded from patients who had indwelling subdural electrodes as part of
      presurgical testing, while BOLD responses were measured in similar brain regions
      in a second set of subjects. Similar BOLD responses were measured in peri
      calcarine and fusiform regions, with both showing monotonic but non-linear
      increases in hemodynamic amplitude with stimulus duration. In sharp contrast,
      very different ERP responses were observed in these same regions, such that
      calcarine electrodes exhibited onset potentials, sustained activity over the
      course of stimulus duration and prominent offset potentials, while fusiform
      electrodes only exhibited onset potentials that did not vary with stimulus
      duration. No duration-related ERP or BOLD changes were observed in LTO.
      Additional analyses revealed no consistent changes in the EEG spectrum across
      different brain sites that correlated with duration-related changes in the BOLD
      response. We conclude that the relation between ERPs and fMRI differs across
      brain regions.

PMID- 14704214
TI  - Functional neuroanatomy of spatial orientation processing in Turner syndrome.
AB  - Turner syndrome (TS), a neurogenetic disorder characterized by the absence of one
      X chromosome in a phenotypic female, is frequently associated with visuospatial
      impairments. We investigated the neural mechanisms underlying deficits in spatial
      orientation processing in TS. Thirteen subjects with TS and 13 age-matched
      typically developing controls underwent neuropsychological assessments and were
      scanned using functional MRI while they performed easy and difficult versions of
      a judgment of line orientation (JLO) task. Controls and subjects with TS
      activated parietal-occipital regions involved in spatial orientation during the
      JLO task. However, activation was significantly less in the TS group. Control
      subjects responded to increased task difficulty by recruiting executive frontal
      areas whereas subjects with TS did not activate alternate brain regions to meet
      increased task demands. Subjects with TS demonstrate activation deficits in
      parietal-occipital and frontal areas during the JLO task. Activation, and
      possibly deactivation, deficits in these areas may be responsible for the
      visuospatial deficits observed in females with TS.

PMID- 14704215
TI  - Dissociable cortical processing of recognizable and non-recognizable biological
      movement: analysing gamma MEG activity.
AB  - Recognition of biological motion is one of the essential ingredients of human
      evolutionary survival. When biological motion is revealed solely by a set of
      light dots on the joints of an invisible human figure, the perceptual system
      reliably distinguishes it from similar configurations. Here, we assessed the
      changes in neuromagnetic cortical responses during visual perception of
      biological motion. Healthy humans saw a randomized set of stimuli consisting of a
      point-light canonical walker and a scrambled configuration in which the spatial
      positions of dots were randomly rearranged on the screen. In separate runs,
      configurations were presented either within an upright or inverted (180 degrees )
      orientation in the image plane. Participants performed a one-back repetition task
      lifting a forefinger in response to the second of two consecutive identical
      stimuli of each type. Both recognizable upright and non-recognizable inverted
      walkers evoke enhancements in oscillatory gamma brain activity (25-30 Hz) over
      the left occipital cortices as early as 100 ms from stimulus onset. Only a
      recognizable upright walker, however, yields further consecutive peaks over the
      parietal (130 ms) and right temporal (170 ms) lobes. Scrambled displays do not
      elicit any increases in the gamma response. The stimulus-specific time course and
      topographic dynamics of cortical oscillatory activity indicate that the brain
      rapidly dissociates spatial coherence and meaning revealed through biological
      movement.

PMID- 14704216
TI  - Regulation by metabotropic glutamate receptor 5 of LTP in the dentate gyrus of
      freely moving rats: relevance for learning and memory formation.
AB  - Group I metabotropic glutamate (mGlu) receptors play a critical role in the
      regulation of hippocampal long-term potentiation (LTP) in vivo. Little is known,
      however, about the contribution of the individual subtypes mGlu1 and mGlu5 to
      learning processes and LTP. We investigated the involvement of mGlu5 in
      hippocampal LTP and spatial learning using the selective antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP). Rats were chronically implanted with recording
      and stimulating electrodes to enable measurement of evoked potentials from the
      medial perforant path - dentate gyrus granule cell synapses. An injection cannula
      was inserted into the ipsilateral cerebral ventricle to enable drug application.
      Experiments were begun 10 days subsequent to the implantation procedure. Robust
      LTP which lasted for over 25 h was generated using 200 Hz tetanization. MPEP,
      applied in concentrations which did not affect basal synaptic transmission, dose
      dependently impaired the induction and expression of LTP. Application of MPEP 5
      min after tetanization inhibited late LTP (>24 h). The effects of daily MPEP
      application on performance in an eight-arm radial maze were evaluated. MPEP
      treated rats showed deficits in reference and working memory performance compared
      to vehicle-treated controls. Rearing, grooming and locomotor activity were
      unaffected in MPEP-treated animals. These data highlight the importance of mGlu5
      for both LTP and spatial learning and emphasize the significance of these
      receptors for information storage on both synaptic and behavioural levels.

PMID- 14704217
TI  - Regional brain activation during concurrent implicit and explicit sequence
      learning.
AB  - We used event-related fMRI to identify the brain regions engaged during explicit
      and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects
      performed a concurrent ESL and ISL task. Behavior showed learning in both
      conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and
      visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL
      there was increased activity in the visual regions on the predictable (i.e.
      learned pattern) trials. With ISL, however, there was a relative decrease in
      activity in visual regions. The opposite patterns in the visual regions highlight
      the different effects of ESL and ISL. The learning process was distinguished from
      the result of learning, by fitting subjects' functional magnetic resonance
      imaging data to their learning curve. This analysis revealed more extensive PFC
      activity during ESL and caudal ACC activity specific for the result of learning
      analysis, when the expected response was violated. Our results suggest a relative
      dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL
      can be viewed as partially distinct but overlapping parallel processes.

PMID- 14704218
TI  - Thinking about actions: the neural substrates of person knowledge.
AB  - Despite an extensive literature on the neural substrates of semantic knowledge,
      how person-related information is represented in the brain has yet to be
      elucidated. Accordingly, in the present study we used functional magnetic
      resonance imaging (fMRI) to investigate the neural correlates of person
      knowledge. Focusing on the neural substrates of action knowledge, participants
      reported whether or not a common set of behaviors could be performed by people or
      dogs. While dogs and people are capable of performing many of the same actions
      (e.g. run, sit, bite), we surmised that the representation of this knowledge
      would be associated with distinct patterns of neural activity. Specifically,
      person judgments were expected to activate cortical areas associated with theory
      of mind (ToM) reasoning. The results supported this prediction. Whereas action
      related judgments about dogs were associated with activity in various regions,
      including the occipital and parahippocampal gyri; identical judgments about
      people yielded activity in areas of prefrontal cortex, notably the right middle
      and medial frontal gyri. These findings suggest that person knowledge may be
      functionally dissociable from comparable information about other animals, with
      action-related judgments about people recruiting neural activity that is
      indicative of ToM reasoning.

PMID- 14704219
TI  - Estrogen replacement increases spinophilin-immunoreactive spine number in the
      prefrontal cortex of female rhesus monkeys.
AB  - While studies have shown that estrogen affects hippocampal spine density and
      function, behavioral studies in humans and nonhuman primates have also implicated
      the prefrontal cortex in the effects of estrogen on cognition. However, the
      potential for similar estrogen-induced increases in spines and synapses in the
      prefrontal cortex has not been investigated in primates. Moreover, it is not
      known if such an estrogen effect would be manifested throughout the neocortex or
      primarily in the regions involved in cognition. Therefore, we investigated the
      effects of estrogen on dendritic spines in the prefrontal and primary visual
      cortices of young rhesus monkeys. Young female monkeys were ovariectomized and
      administered either estradiol cypionate or vehicle by intramuscular injection.
      Using an antibody against the spine-associated protein, spinophilin, spine
      numbers were estimated in layer I of area 46 and in layer I of the opercular
      portion of area V1 (V1o). Spine numbers in layer I of area 46 were significantly
      increased (55%) in the ovariectomy + estrogen group compared to the ovariectomy +
      vehicle group, yet spine numbers in layer I of area V1o were equivalent across
      the two groups. The present results suggest that estrogen's effects on synaptic
      organization influence select neocortical layers and regions in a primate model,
      and provide a morphological basis for enhanced prefrontal cortical functions
      following estrogen replacement.

PMID- 14704220
TI  - Acute stress-induced changes in hippocampal/prefrontal circuits in rats: effects
      of antidepressants.
AB  - Acute stress inhibits long-term potentiation (LTP) at synapses from the
      hippocampus to prefrontal cortex in the rat, a model of the dysfunction in the
      anterior cingulate/orbitofrontal cortices which has been observed in human
      depression. We demonstrate that the antidepressants tianeptine and, to a lesser
      extent, fluoxetine, are able to reverse the impairment in LTP, a measure of
      frontal synaptic plasticity, caused by stress on an elevated platform. LTP was
      induced by stimulation of hippocampal outflow. Beneficial effects on neuronal
      plasticity, defined as a reversal of the effects of stress in this paradigm, can
      be considered as a new animal model for the impact of stress on
      hippocampal/frontal circuits, a key target in psychiatric diseases.

PMID- 14704221
TI  - Tracing surfactant transformation from cellular release to insertion into an air
      liquid interface.
AB  - Pulmonary surfactant is secreted by alveolar type II cells as lipid-rich, densely
      packed lamellar body-like particles (LBPs). The particulate nature of released
      LBPs might be the result of structural and/or thermodynamic forces. Thus
      mechanisms must exist that promote their transformation into functional units. To
      further define these mechanisms, we developed methods to follow LBPs from their
      release by cultured cells to insertion in an air-liquid interface. When released,
      LBPs underwent structural transformation, but did not disperse, and typically
      preserved a spherical appearance for days. Nevertheless, they were able to modify
      surface tension and exhibited high surface activity when measured with a
      capillary surfactometer. When LBPs inserted in an air-liquid interface were
      analyzed by fluorescence imaging microscopy, they showed remarkable structural
      transformations. These events were instantaneous but came to a halt when the
      interface was already occupied by previously transformed material or when surface
      tension was already low. These results suggest that the driving force for LBP
      transformation is determined by cohesive and tensile forces acting on these
      particles. They further suggest that transformation of LBPs is a self-regulated
      interfacial process that most likely does not require structural intermediates or
      enzymatic activation.

PMID- 14704222
TI  - Mechanisms of organophosphate insecticide-induced airway hyperreactivity.
AB  - It has been suggested that pesticide exposure may be a contributing factor
      underlying the increased incidence of asthma in the United States and other
      industrialized nations. To test this hypothesis, airway hyperreactivity was
      measured in guinea pigs exposed to chlorpyrifos, a widely used organophosphate
      pesticide. Electrical stimulation of the vagus nerves caused frequency-dependent
      bronchoconstriction that was significantly potentiated in animals 24 h or 7 days
      after a single subcutaneous injection of either 390 mg/kg or 70 mg/kg of
      chlorpyrifos, respectively. Mechanisms by which chlorpyrifos may cause airway
      hyperreactivity include inhibition of acetylcholinesterase (AChE) or dysfunction
      of M3 muscarinic receptors on airway smooth muscle or of autoinhibitory M2
      muscarinic receptors on parasympathetic nerves in the lung. AChE activity in the
      lung was significantly inhibited 24 h after treatment with 390 mg/kg of
      chlorpyrifos, but not 7 days after injection of 70 mg/kg of chlorpyrifos. Acute
      exposure to eserine (250 microg/ml) also significantly inhibited lung AChE but
      did not potentiate vagally induced bronchoconstriction. Neuronal M2 receptor
      function was tested using the M2 agonist pilocarpine, which inhibits vagally
      induced bronchoconstriction in control animals. In chlorpyrifos-treated animals,
      pilocarpine dose-response curves were shifted significantly to the right,
      demonstrating decreased responsiveness of neuronal M2 receptors. In contrast,
      chlorpyrifos treatment did not alter methacholine-induced bronchoconstriction,
      suggesting that chlorpyrifos does not alter M3 muscarinic receptor function on
      airway smooth muscle. These data demonstrate that organophosphate insecticides
      can cause airway hyperreactivity in the absence of AChE inhibition by decreasing
      neuronal M2 receptor function.

PMID- 14704223
TI  - Endothelial cell P-selectin mediates a proinflammatory and prothrombogenic
      phenotype in cerebral venules of sickle cell transgenic mice.
AB  - Whereas the adhesion of leukocytes and erythrocytes to vascular endothelium has
      been implicated in the vasooclusive events associated with sickle cell disease,
      the role of platelet-vessel wall interactions in this process remains undefined.
      The objectives of this study were to: 1) determine whether the adhesion of
      platelets and leukocytes in cerebral venules differs between sickle cell
      transgenic (betaS) mice and their wild-type (WT) counterparts (C57Bl/6) under
      both resting and posthypoxic conditions, and 2) define the contributions of P
      selectin to these adhesion processes. Animals were anesthetized, and platelet and
      leukocyte interactions with endothelial cells of cerebral postcapillary venules
      were monitored and quantified using intravital fluorescence microscopy in WT,
      betaS, and chimeric mice produced by transplanting bone marrow from WT or betaS
      mice into WT or P-selectin-deficient (P-sel(-/-)) mice. Platelet and leukocyte
      adhesion to endothelial cells in both unstimulated and posthypoxic betaS mice
      were significantly elevated over WT levels. Chimeric mice involving bone marrow
      transfer from betaS mice to P-sel(-/-) mice exhibited a profound attenuation of
      both platelet and leukocyte adhesion compared with betaS bone marrow transfer to
      WT mice. These findings indicate that betaS mice assume both an inflammatory and
      prothrombogenic phenotype, with endothelial cell P-selectin playing a major role
      in mediating these microvascular responses.

PMID- 14704224
TI  - Estradiol-induced expression of N(+)-K(+)-ATPase catalytic isoforms in rat
      arteries: gender differences in activity mediated by nitric oxide donors.
AB  - We tested the hypothesis that previously demonstrated gender differences in ACh
      induced vascular relaxation could involve diverse Na(+)-K(+)-ATPase functions. We
      determined Na(+)-K(+)-ATPase by measuring arterial ouabain-sensitive 86Rb uptake
      in response to ACh. We found a significant increase of Na+ pump activity only in
      aortic rings from female rats (control 206 +/- 11 vs. 367 +/- 29 nmol 86Rb/K.min(
      1).g wt tissue(-1); P < 0.01). Ovariectomy eliminated sex differences in Na(+)
      K(+)-ATPase function, and chronic in vivo hormone replacement with 17beta
      estradiol restored the ACh effect on Na(+)-K(+)-ATPase. Because ACh acts by
      enhancing production of NO, we examined whether the NO donor sodium nitroprusside
      (SNP) mimics the action of ACh on Na(+)-K(+)-ATPase activity. SNP increased
      ouabain-sensitive 86Rb uptake in denuded female arteries (control 123 +/- 7 vs.
      197 +/- 12 nmol 86Rb/K.min(-1).g wt tissue(-1); P < 0.05). Methylene blue (an
      inhibitor of guanylate cyclase) and KT-5823 (a cGMP-dependent kinase inhibitor)
      blocked the stimulatory action of SNP. Exposure of female thoracic aorta to the
      Na+/K+ pump inhibitor ouabain significantly decreased SNP-induced and ACh
      mediated relaxation of aortic rings. At the molecular level, Western blot
      analysis of arterial tissue revealed significant gender differences in the
      relative abundance of catalytic isoforms of Na(+)-K(+)-ATPase. Female-derived
      aortas exhibited a greater proportion of alpha2-isoform (44%) compared with male
      derived aortas. Furthermore, estradiol upregulated the expression of alpha2 mRNA
      in male arterial explants. Our results demonstrate that enhancement of ACh
      induced relaxation observed in female rats may be in part explained by 1) NO
      dependent increased Na(+)-K(+)-ATPase activity in female vascular tissue and 2)
      greater abundance of Na(+)-K(+)-ATPase alpha2-isoform in females.

PMID- 14704225
TI  - Heterogeneous connexin43 expression produces electrophysiological heterogeneities
      across ventricular wall.
AB  - Recently we found that electrophysiological (EP) heterogeneities between
      subepicardial and midmyocardial cells can form a substrate for reentrant
      ventricular arrhythmias. However, cell-to-cell coupling through gap junctions is
      expected to attenuate transmural heterogeneities between cell types spanning the
      ventricular wall. Because connexin43 (Cx43) is the principal ventricular gap
      junction protein, we hypothesized that transmural EP heterogeneities are in part
      produced by heterogeneous Cx43 expression across the ventricular wall. The left
      ventricles of eight dogs were sectioned to expose the transmural surface. To
      determine whether heterogeneous Cx43 expression influenced EP function, high
      resolution transmural optical mapping of the arterially perfused canine wedge
      preparation was used to measure transmural conduction velocity (thetaTM),
      dV/dt(max), transmural space constant (lambdaTM), and transmural gradients of
      action potential duration (APD). Relative Cx43 expression, quantified by confocal
      immunofluorescence, was significantly lower (by 24 +/- 17%; P < 0.05) in
      subepicardial compared with deeper layers. Importantly, reduced subepicardial
      Cx43 was associated with transmural heterogeneities of EP function evidenced by
      selectively reduced subepicardial thetaTM (by 18 +/- 9%; P < 0.05) compared with
      deeper layers. In subepicardial regions, dV/dt(max) was fastest (by 19 +/- 15%)
      and lambdaTM was smallest (by 18.1 +/- 2%), which suggests that conduction
      slowing was attributable to localized uncoupling rather than reduced
      excitability. The maximum transmural APD gradients occurred in the same regions
      where Cx43 expression was lowest; this suggests that Cx43 expression patterns
      served to maintain APD gradients across the transmural wall. These data
      demonstrate that heterogeneous Cx43 expression is closely associated with
      functionally significant EP heterogeneities across the transmural wall.
      Therefore, Cx43 expression patterns can potentially contribute to arrhythmic
      substrates that are dependent on transmural electrophysiological heterogeneities.

PMID- 14704226
TI  - Administration of a CO-releasing molecule at the time of reperfusion reduces
      infarct size in vivo.
AB  - Although carbon monoxide (CO) has traditionally been viewed as a toxic gas,
      increasing evidence suggests that it plays an important homeostatic and
      cytoprotective role. Its therapeutic use, however, is limited by the side effects
      associated with CO inhalation. Recently, transition metal carbonyls have been
      shown to be a safe and effective means of transporting and releasing CO groups in
      vivo. The goal of the present study was to test whether a water-soluble CO
      releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces
      infarct size in vivo when given in a clinically relevant manner, i.e., at the
      time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion
      followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60
      min intravenous infusion starting 5 min before reperfusion) or equivalent doses
      of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial
      blood pressure or heart rate. The region at risk did not differ in control and
      treated mice (44.5 +/- 3.5% vs. 36.5 +/- 1.6% of the left ventricle,
      respectively). However, infarct size was significantly smaller in treated mice
      [25.8 +/- 4.9% of the region at risk (n = 13) vs. 47.7 +/- 3.8% (n = 14), P <
      0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These
      results suggest that a novel class of drugs, CO-releasing molecules, can be
      useful to limit myocardial ischemia-reperfusion injury in vivo.

PMID- 14704227
TI  - Atorvastatin completely inhibits VEGF-induced ACE upregulation in human
      endothelial cells.
AB  - Angiotensin-converting enzyme (ACE) plays an important role in the
      pathophysiology of cardiovascular disease. We investigated whether atorvastatin,
      a powerful agent for the prevention and treatment of cardiovascular disease,
      influences ACE production in endothelial cells. Human umbilical cord vein
      endothelial cells were treated with VEGF (476 pM), which induced ACE
      upregulation. Cotreatment with atorvastatin (0.1-10 microM) dose dependently
      inhibited VEGF-induced ACE upregulation. In the presence of mevalonate (100
      microM), atorvastatin failed to downregulate VEGF-induced ACE production.
      Cotreatment of the cells with either farnesylpyrophosphate (FPP; 5 microM) or
      geranylgeranylpyrophosphate (GGPP; 5 microM) partially inhibited the suppressive
      effect of atorvastatin. Pretreatment of the cells with Rho-associated protein
      kinase inhibitor, Y-27632 (10 microM), partially inhibited VEGF-induced ACE
      upregulation. VEGF (476 pM) caused PKC phosphorylation, which was inhibited by
      cotreatment of the cells with atorvastatin. Atorvastatin inhibited VEGF-induced
      ACE upregulation probably by inhibiting PKC phosphorylation. This effect was
      mediated via inhibition of the mevalonate pathway. ACE downregulation may be an
      additional beneficial effect of statins in the treatment of cardiovascular
      disease.

PMID- 14704228
TI  - Effects of C-type natriuretic peptide on ionic currents in mouse sinoatrial node:
      a role for the NPR-C receptor.
AB  - The effects of C-type natriuretic peptide (CNP) on heart rate and ionic currents
      were demonstrated by recording the ECG from adult mice and performing voltage
      clamp experiments on single sinoatrial (SA) node cells isolated from mouse heart.
      The selective natriuretic peptide type C receptor (NPR-C) agonist cANF (10(-7) M)
      significantly decreased heart rate in the presence of isoproterenol (5 x 10(-9)
      M), as indicated by an increase in the R-R interval of ECGs obtained from
      Langendorff-perfused hearts. Voltage-clamp measurements in enzymatically isolated
      single pacemaker myocytes revealed that CNP (10(-8) M) and cANF (10(-8) M)
      significantly inhibited L-type Ca2+ current [ICa(L)]. These findings suggest that
      the CNP effect on this current is mediated by NPR-C. Further support for an NPR-C
      mediated inhibition of ICa(L) in SA node myocytes was obtained by altering the
      functional coupling between the G protein Gi and NPR-C. In these experiments, a
      "Gi-activator peptide," which consists of a 17-amino acid segment of NPR-C
      containing a specific Gi protein-activator sequence, was dialyzed into SA node
      myocytes. This peptide decreased ICa(L) significantly, suggesting that NPR-C
      activation can result in a reduction in ICa(L) when CNP is bound and the Gi
      protein pathway is activated. This effect of CNP appears to be selective for
      ICa(L), because the hyperpolarization-activated current was unaffected by CNP or
      cANF. These results provide the first demonstration that CNP has a negative
      chronotropic effect on heart rate and suggest that this effect is mediated by
      selectively activating NPR-C and reducing ICa(L) through coupling to Gi protein.

PMID- 14704229
TI  - Inflammation- and ischemia-induced shedding of venular glycocalyx.
AB  - Alterations in the composition of the glycocalyx of venular endothelium in
      postcapillary venules (rat mesentery) were explored in models of inflammation and
      ischemia-reperfusion injury. Lectins were covalently linked to fluorescently
      labeled microspheres (0.1-microm diameter) or directly labeled with FITC.
      Adhesion of lectins specific for glucose and galactose residues of
      glycosaminoglycans (GAGs) and other components of the endothelial glycocalyx
      decreased dramatically after superfusion of the mesentery with the
      chemoattractant N-formylmethionyl-leucyl-phenylalanine and during reperfusion
      after 60-min ischemia. These reductions were significantly attenuated by
      superfusion with pertussis toxin (PTX), suggesting that shedding of glycocalyx
      was mediated by G proteins. Adhesion of microspheres linked with antibody for
      syndecan-1, a major proteoglycan to which GAGs are bound, revealed increased
      labeling as GAGs were lost and permitted greater numbers of spheres to adhere to
      the protein core, which was not shed. Induction of ischemia by occluding proximal
      microvessels for 60 min resulted in a 40% increase in galactosaminoglycans and a
      15% increase in glucosaminoglycans on the endothelium, which was not inhibited by
      PTX. Reperfusion of vessels led to a rapid loss of GAGs that was inhibited by
      pretreatment with PTX, with 40% of galactosaminoglycans and 25% of
      glucosaminoglycans accumulated being removed by G protein-mediated shedding and
      the remainder freely convected away by fluid shear. We conclude that the
      composition of the glycocalyx results from a balance of the rate of biosynthesis
      of GAGs by the endothelial cell and their shedding, which may be mediated by
      intracellular and/or membrane-bound proteases or lyases released or activated by
      G protein signaling.

PMID- 14704230
TI  - Molecular cloning, functional analysis, and RNA expression analysis of
      connexin45.6: a zebrafish cardiovascular connexin.
AB  - In the vertebrate cardiovascular system, gap junctions function in intercellular
      communication essential for both the coordinated propagation of the heartbeat and
      the control of vasomotor responses in the vascular system. Connexins, the protein
      subunits of gap junctions, are coded by a multigene family. In this study, a
      connexin gene (zfCx45.6), which exhibits 53% amino acid identity to chick Cx42,
      was cloned from zebrafish genomic DNA. With the use of the LN54 radiation hybrid
      panel, zfCx45.6 was mapped to zebrafish linkage group 9. Northern blots and RT
      PCR revealed the presence of zfCx45.6 mRNA in the embryo before 2 h
      postfertilization (hpf) and then again beginning at about 12 hpf, after which
      time no major changes in relative expression levels were detected. In the adult,
      zfCx45.6 mRNA continued to be detected in the heart, as well as the brain, liver,
      and ovary, but not the lens. Whole mount in situ hybridization revealed zfCx45.6
      mRNA was expressed at high levels in the major vessels of the entire embryo and
      in both the atrium and ventricle of the adult heart. Expression of zfCx45.6
      channels in paired Xenopus oocytes produced high levels of intercellular coupling
      that was voltage sensitive. With the previous isolation of zebrafish Cx43 and
      Cx43.4, zebrafish orthologues have now been isolated for three of the four
      connexins expressed in the mammalian cardiovascular system.

PMID- 14704231
TI  - Localization of VEGFR-2 and PLD2 in endothelial caveolae is involved in VEGF
      induced phosphorylation of MEK and ERK.
AB  - To clarify the role of caveolae in VEGF/VEGF receptor-2 (VEGFR-2)-mediated
      signaling cascades, primary cultured human umbilical vein endothelial cells
      (HUVECs) were fractionated to isolate caveolae-enriched cell membranes.
      Interestingly, VEGFR-2, phospholipase D2 (PLD2), and Ras were enriched in
      caveolae-enriched fractions. Moreover, VEGF increased PLD activity in a time- and
      dose-dependent manner in HUVECs, whereas a ligand specific for VEGFR-1 placental
      growth factor did not change PLD activity. A PLD inhibitor, 1-butanol, almost
      completely suppressed VEGF-induced ERK phosphorylation and cellular
      proliferation, whereas the negative control for 1-butanol, 3-butanol, did not
      produce significant changes. Addition of phosphatidic acid negated the 1-butanol
      induced suppression. Pharmacological analyses using several inhibitors indicated
      that PKC-delta regulates the VEGF-induced activation of PLD/ERK. Thus PLD2 could
      be involved in MEK/ERK signaling cascades that are induced by the VEGF/VEGFR
      2/PKC-delta pathway in endothelial cells. Pretreatment with the cholesterol
      depletion agent methyl-beta-cyclodextrin (MbetaCD) almost completely disassembled
      caveolar structures, whereas the addition of cholesterol to MbetaCD-treated cells
      restored caveolar structures. Pretreatment with MbetaCD largely abolished
      phosphorylation of MEK/ERK by VEGF, whereas the addition of cholesterol restored
      VEGF-induced MEK/ERK phosphorylations. These results indicate that intact
      caveolae are required for the VEGF/VEGFR-2-mediated MEK/ERK signaling cascade.

PMID- 14704232
TI  - Exercise training improves cardiac function-related gene levels through thyroid
      hormone receptor signaling in aged rats.
AB  - Exercise training improves the aging-induced downregulation of myosin heavy chain
      (MHC) and sarcoplasmic reticulum (SR) Ca(2+)-ATPase, which participate in the
      regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR),
      a transcriptional activator, affected the regulation of gene expression of MHC
      and SR Ca(2+)-ATPase. We hypothesized that myocardial TR signaling contributes to
      a molecular mechanism of exercise training-induced improvement of MHC and SR
      Ca(2+)-ATPase genes with cardiac function in old age. We investigated whether TR
      signaling and gene expression of MHC and SR Ca(2+)-ATPase in the aged heart are
      affected by exercise training, using the hearts of sedentary young rats (4 mo
      old), sedentary aged rats (23 mo old), and trained aged rats (23 mo old, swimming
      training for 8 wk). Trained aged rats showed improvement in cardiac function.
      Expression of TR-alpha1 and TR-beta1 proteins in the heart were significantly
      lower in sedentary aged rats than in sedentary young rats and were significantly
      higher in trained aged rats than in sedentary aged rats. The activity of TR DNA
      binding to the transcriptional regulatory region in the alpha-MHC and SR Ca(2+)
      ATPase genes and the mRNA and protein expression of alpha-MHC and SR Ca(2+)
      ATPase in the heart and plasma 3,3'-triiodothyronine and thyroxine levels were
      altered in association with changes in the myocardial TR protein levels. These
      findings suggest that exercise training improves the aging-induced downregulation
      of myocardial TR signaling-mediated transcription of MHC and SR Ca(2+)-ATPase
      genes, thereby contributing to the improvement of cardiac function in trained
      aged hearts.

PMID- 14704233
TI  - Dynamic changes in expression of myosin phosphatase in a model of portal
      hypertension.
AB  - Myosin phosphatase is a target for signaling pathways that modulate calcium
      sensitivity of force production in smooth muscle. Myosin phosphatase targeting
      subunit 1 (MYPT1) isoforms are generated by cassette-type alternative splicing of
      exons in the central and 3' portion of the transcript. Exclusion of the 3'
      alternative exon, coding for the leucine zipper (LZ)-positive MYPT1 isoform, is
      associated with the ability to desensitize to calcium (relax) in response to
      NO/cGMP-dependent signaling. We examined expression of MYPT1 isoforms and smooth
      muscle phenotype in normal rat vessels and in a prehepatic model of portal
      hypertension characterized by arteriolar dilation. The large capacitance vessels,
      aorta, pulmonary artery, and inferior vena cava expressed predominantly the 3'
      exon-out/LZ-positive MYPT1 isoform. The first-order mesenteric resistance artery
      (MA1) and portal vein (PV) expressed severalfold higher levels of MYPT1 with
      predominance of the 3' exon-included/LZ-negative isoform. There was minor
      variation in the presence of the MYPT1 central alternative exons. Myosin heavy
      and light chain splice variants in part cosegregated with MYPT1 isoforms. In
      response to portal hypertension induced by PV ligature, abundance of MYPT1 in PV
      and MA1 was significantly reduced and switched to the LZ-positive isoform. These
      changes were evident within 1 day of PV ligature and were maintained for up to 10
      days before reverting to control values at day 14. Alteration of MYPT1 expression
      was part of a complex change in protein expression that can be generalized as a
      modulation from a phasic (fast) to a tonic (slow) contractile phenotype.
      Implications of vascular smooth muscle phenotypic diversity and reversible
      phenotypic modulation in portal hypertension with regards to regulation of blood
      flow are discussed.

PMID- 14704234
TI  - Disodium cromoglycate stabilizes mast cell degranulation while reducing the
      number of hemoglobin-induced microvascular leaks in rat mesentery.
AB  - Blood substitutes, such as diaspirin cross-linked Hb (DBBF-Hb), have been
      considered for use during blood transfusions. Unfortunately, bolus injection of
      modified Hb has been shown to rapidly increase the leakage of microvessels to
      plasma albumin. This effect may result from production of excess reactive oxygen
      species (ROS) and could be linked to the observed increase in degranulated mast
      cells (DMC). Disodium cromoglycate (cromolyn) stabilizes mast cells and therefore
      might minimize the venular permeability in the rat mesentery. In 10 anesthetized
      Sprague-Dawley rats, the mesenteric preparation was continuously suffused with
      cromolyn while the microvasculature was filled with DBBF-Hb solution (10 mg/ml)
      for 10 min. Six animals received cromolyn pretreatment [two intravascular
      injections over 30 min (experiment A)] and four animals received pretreatment
      with 2% HEPES-buffered saline (HBS)-BSA (experiment B). Two more animals were
      pretreated with HBS-BSA without DBBF-Hb infusion but with cromolyn suffusion
      (experiment C). Another set of experiments was performed on five animals without
      cromolyn suffusion or any pretreatment but with DBBF-Hb infusion (experiment D).
      All groups then received a 1-min perfusion of FITC-albumin, fixation for 60 min,
      and microscopic examination. Experiments A and B demonstrated a significant
      reduction in the number of venular leaks and DMC compared with experiment D, but
      not in the area of venular leaks. These results suggest mast cell degranulation
      is not a major contributor to microvascular leakage induced by DBBF-Hb.

PMID- 14704236
TI  - Simple gestures.

PMID- 14704235
TI  - Intracellular Ca dynamics in ventricular fibrillation.
AB  - In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are
      bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and
      Cai affects ionic currents regulating action potential duration (APD). Although
      Cai reliably and consistently tracks Vm at normal heart rates, it is possible
      that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit
      intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations
      in APD and refractoriness that influence wavebreak during ventricular
      fibrillation (VF). In this study, we tested this hypothesis by examining the
      extent to which Cai is associated with Vm during VF. Cai transients were mapped
      optically in isolated arterially perfused swine right ventricles using the
      fluorescent dye rhod 2 AM while intracellular membrane potential was
      simultaneously recorded either locally with a microelectrode (5 preparations) or
      globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual
      information (MI) is a quantitative statistical measure of the extent to which
      knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI
      was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/
      0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001).
      Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13)
      compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001).
      Spatially, Cai waves usually bore no relationship to membrane depolarization
      waves during nonreentrant fractionated waves typical of VF, whereas they tracked
      each other closely during pacing and VT. The dominant frequencies of Vm and Cai
      signals analyzed by fast Fourier transform were similar during VT but differed
      significantly during VF. Cai is closely associated with Vm closely during pacing
      and VT but not during VF. These findings suggest that during VF, non-voltage
      gated Cai release events occur and may influence wavebreak by altering Vm and APD
      locally.

PMID- 14704238
TI  - Randomized trial of intracervical versus posterior fornix dinoprostone for
      induction of labor.
AB  - OBJECTIVE: To investigate whether intracervical placement of a sustained-release
      dinoprostone insert decreased the length of time to delivery when compared with
      placement in the posterior fornix. METHODS: Sixty-three patients were randomized
      to intracervical (n = 33) or posterior fornix (n = 30) placement of the initial
      dose. Dinoprostone was placed under direct visualization with a vaginal speculum
      and packing forceps. The patients and staff were blinded to the site of
      placement. Multiple end points were examined throughout labor. Student t test,
      Fisher exact test, Wilcoxon test, Mann-Whitney U test, and chi2 analyses were
      performed when appropriate. A P value of less than.05 was considered significant.
      RESULTS: Forty-six patients who required only a single dose of dinoprostone had a
      reduced time to delivery with intracervical (n = 24; 11.70 hours) compared with
      intravaginal (n = 22; 16.20 hours) placement (P =.025). There was also a reduced
      time to active labor (intracervical = 8.25 hours, posterior fornix = 11.50 hours;
      P =.083), ruptured membranes (intracervical = 10.25 hours, posterior fornix =
      12.00 hours; P =.047), and request for initial pain medications (intracervical =
      5.00 hours, posterior fornix = 11.25 hours; P =.025) with intracervical
      placement. There was no difference in number of patients managed with artificial
      rupture of membranes. There was no difference in maternal age, race, parity,
      maternal height or weight, or indication for induction. There was also no
      difference in cesarean delivery rate, antepartum fever, hyperstimulation, Apgar
      scores, birth weight, or umbilical artery pH. CONCLUSION: In patients who respond
      to a single sustained-release dinoprostone insert, intracervical placement
      decreases time to delivery without increasing the cesarean delivery rate,
      infectious morbidity, or other complications of labor.

PMID- 14704237
TI  - Asthma during pregnancy.
AB  - OBJECTIVE: To determine neonatal and maternal outcomes stratified by asthma
      severity during pregnancy by using the 1993 National Asthma Education Program
      Working Group on Asthma and Pregnancy definitions of asthma severity. The primary
      hypothesis was that moderate or severe asthmatics would have an increased
      incidence of delivery at <32 weeks of gestation compared with nonasthmatic
      controls. METHODS: This was a multicenter, prospective, observational cohort
      study conducted over 4 years at 16 university hospital centers. Asthma severity
      was defined according to the National Asthma Education Program Working Group on
      Asthma and Pregnancy classification and modified to include medication
      requirements. This study had 80% power to detect a 2- to 3-fold increase in
      delivery less than 32 weeks of gestation among the cohort with the moderate or
      severe asthma compared with controls. Secondary outcome measures included
      obstetrical and neonatal outcomes. RESULTS: The final analysis included 881
      nonasthmatic controls, 873 with mild asthma, 814 with moderate, and 52 with
      severe asthma. There were no significant differences in the rates of preterm
      delivery less than 32 weeks (moderate or severe 3.0%, mild 3.4%, controls 3.3%; P
      =.873) or less than 37 weeks of gestation. There were no significant differences
      for neonatal outcomes except discharge diagnosis of neonatal sepsis among the
      mild group compared with controls, adjusted odds ratio 2.9, 95% confidence
      interval 1.2, 6.8. There were no significant differences for maternal
      complications except for an increase in overall cesarean delivery rate among the
      moderate-or-severe group compared with controls (adjusted odds ratio 1.4, 95%
      confidence interval 1.1, 1.8). CONCLUSION: Asthma was not associated with a
      significant increase in preterm delivery or other adverse perinatal outcomes
      other than a discharge diagnosis of neonatal sepsis. Cesarean delivery rate was
      increased among the cohort with moderate or severe asthma. LEVEL OF EVIDENCE: II
      2

PMID- 14704239
TI  - Cervical ripening with transcervical foley catheter and the risk of uterine
      rupture.
AB  - OBJECTIVE: To estimate whether the rate of uterine rupture in patients with a
      previous cesarean delivery is related to labor induction and/or cervical ripening
      using transcervical Foley catheter. METHODS: Charts of all patients who had a
      trial of labor after a previous cesarean delivery in our institution between 1988
      and 2002 were reviewed. The rates of successful vaginal birth after cesarean
      delivery and uterine rupture in patients with spontaneous labor (control group)
      were compared with those of patients who underwent a labor induction by means of
      amniotomy with or without oxytocin and patients who underwent a labor
      induction/cervical ripening using a transcervical Foley catheter. Logistic
      regression analysis was performed to adjust for confounding variables. RESULTS:
      Of 2479 patients, 1807 had a spontaneous labor, 417 had labor induced by
      amniotomy with or without oxytocin, and 255 had labor induced by using
      transcervical Foley catheter. The rate of successful vaginal birth after cesarean
      delivery was significantly different among the groups (78.0% versus 77.9% versus
      55.7%, P <.001), but not the rate of uterine rupture (1.1% versus 1.2% versus
      1.6%, P =.81). After adjusting for confounding variables, the odds ratio (OR) for
      successful vaginal birth after cesarean delivery was 0.68 (95% confidence
      interval [CI] 0.41, 1.15), and the OR for uterine rupture was 0.47 (95% CI 0.06,
      3.59) in patients who underwent an induction of labor using a transcervical Foley
      catheter when compared with patients with spontaneous labor. CONCLUSION: Labor
      induction using a transcervical Foley catheter was not associated with an
      increased risk of uterine rupture.

PMID- 14704240
TI  - Management of pregnancies complicated by anti-c isoimmunization.
AB  - OBJECTIVE: To review cases of anti-c isoimmunization and determine the most
      appropriate management strategies. METHODS: We performed a review of 102
      pregnancies managed at The Ohio State University from 1967 to 2001 for anti-c
      isoimmunization. Of these, 55 had complete data and are included in this report.
      Information collected included serum titers, deltaOD450 values, Liley zones,
      fetal and neonatal hemoglobin levels and antigen typing, neonatal direct
      antiglobulin test, and neonatal outcomes. The appropriateness of traditional
      management was then evaluated. RESULTS: Of the 55 pregnancies, 46 had fetuses
      with positive direct antiglobulin test, and nine pregnancies had unaffected
      fetuses. Of the affected neonates, 12 (26%) had serious hemolytic disease of the
      newborn. Of these 12, 8 required fetal transfusion, and the remaining 4 newborns
      had hemoglobin levels of less than 10 g/dL at the time of delivery. A titer of
      1:32 or greater or the presence of hydrops fetalis identified all such fetuses.
      There were 58 amniocenteses performed for deltaOD450 When plotted on modified
      Liley graphs, deltaOD450 values corresponded to disease severity. There were no
      perinatal deaths attributable to anti-c hemolytic disease of the newborn.
      CONCLUSION: Anti-c isoimmunization might cause significant fetal and newborn
      hemolytic disease. A titer of 1:32 or greater or evidence of hydrops fetalis
      identified all the serious hemolytic disease at our institution. The significance
      of antibody titers and deltaOD450 values was similar to Rh-D sensitized
      pregnancies, and management by the same modalities is appropriate.

PMID- 14704241
TI  - Levator ani muscle stretch induced by simulated vaginal birth.
AB  - OBJECTIVE: To develop a three-dimensional computer model to predict levator ani
      muscle stretch during vaginal birth. METHODS: Serial magnetic resonance images
      from a healthy nulliparous 34-year-old woman, published anatomic data, and
      engineering graphics software were used to construct a structural model of the
      levator ani muscles along with related passive tissues. The model was used to
      quantify pelvic floor muscle stretch induced during the second stage of labor as
      a model fetal head progressively engaged and then stretched the iliococcygeus,
      pubococcygeus, and puborectalis muscles. RESULTS: The largest tissue strain
      reached a stretch ratio (tissue length under stretch/original tissue length) of
      3.26 in medial pubococcygeus muscle, the shortest, most medial and ventral
      levator ani muscle. Regions of the ileococcygeus, pubococcygeus, and puborectalis
      muscles reached maximal stretch ratios of 2.73, 2.50, and 2.28, respectively.
      Tissue stretch ratios were proportional to fetal head size: For example,
      increasing fetal head diameter by 9% increased medial pubococcygeus stretch by
      the same amount. CONCLUSION: The medial pubococcygeus muscles undergo the largest
      stretch of any levator ani muscles during vaginal birth. They are therefore at
      the greatest risk for stretch-related injury.

PMID- 14704242
TI  - Clinical examination and dynamic magnetic resonance imaging in vaginal vault
      prolapse.
AB  - OBJECTIVE: To estimate the role of dynamic magnetic resonance imaging (MRI) as a
      diagnostic tool in the evaluation of vaginal apex prolapse in women with previous
      hysterectomy. METHODS: Clinical examinations were performed on 51 women
      presenting with symptoms of prolapse. A preoperative dynamic MRI assessment was
      performed. The mid pubic line was the reference level used for prolapse grading.
      The parameters of analysis included 1). correlation by compartments of clinical
      and MRI grading of prolapse, 2). assessment of the accuracy of clinical
      examination of the middle compartment, and 3). identification of any additional
      information provided by MRI. All MRI films were analyzed and validated by the
      same two observers. RESULTS: Analysis of each compartment separately revealed
      poor correlation between clinical and MRI assessment. Of the 51 cases with
      clinical vault prolapse, 27 (52.9%) cases were clinically overdiagnosed, 3 (6%)
      were underdiagnosed, and there was agreement in 21 (41.1%) when compared with MRI
      findings. Postoperative follow-up of the 18 (85%) patients who underwent
      colposacropexy after intraoperative assessment revealed the presence of cystocele
      in 4 (26.6%) occasions and rectocele in 3 (20%), which had been detected on MRI
      but not confirmed intraoperatively. CONCLUSION: There is poor correlation between
      clinical and MRI findings when assessing vaginal apex prolapse. Magnetic
      resonance imaging allows the identification of other prolapsing compartments and
      may be a complementary diagnostic tool for the diagnosis of complex vaginal apex
      prolapse.

PMID- 14704243
TI  - Interstitial pregnancy: results generated from the Society of Reproductive
      Surgeons Registry.
AB  - OBJECTIVE: To summarize management of interstitial pregnancy and its outcome
      among 32 reported cases in the world. METHODS: From 1999 to 2002, 32 cases of
      interstitial pregnancy were reported to the registry of the Society of
      Reproductive Surgeons. The participants completed a five-page questionnaire
      regarding when and how diagnosis was made, the characteristics of the pregnancy,
      treatment modalities, and subsequent reproductive outcome. RESULTS: History of
      ipsilateral salpingectomy was encountered in 37.5% of patients, and the diagnosis
      was made by ultrasound in 71.4% of the patients. Eight women were treated with
      methotrexate either systemically (n = 4), locally under ultrasound guidance (n =
      2), or under laparoscopic guidance (n = 2). Eleven patients were treated by
      laparoscopy and 13 by laparotomy. Three patients failed systemic methotrexate
      treatment and subsequently required surgery. Persistently elevated serum beta
      human chorionic gonadotropin levels were found in one patient after laparoscopic
      cornual excision, and she was successfully treated with methotrexate. Fourteen
      cases (43.7%) of rupture of interstitial pregnancy were found. This included five
      cases (15.6%) of heterotopic pregnancy; all were the results of in vitro
      fertilization, and all ruptured at the time of diagnosis. Subsequent pregnancy
      was achieved in ten patients. No uterine rupture was encountered during pregnancy
      or labor. CONCLUSION: Ipsilateral salpingectomy, previous ectopic pregnancy, and
      in vitro fertilization are predisposing factors for interstitial pregnancy.
      Contrary to previous belief, rupture of interstitial pregnancy occurs relatively
      early in pregnancy. In selected patients, laparoscopic cornual excision is a
      viable treatment option.

PMID- 14704244
TI  - Increased infertility with age in men and women.
AB  - OBJECTIVE: To estimate the effects of aging on the percentage of outwardly
      healthy couples who are sterile (completely unable to conceive without assisted
      reproduction) or infertile (unable to conceive within a year of unprotected
      intercourse). METHODS: A prospective fecundability study was conducted in a
      sample of 782 couples recruited from 7 European centers for natural family
      planning. Women aged 18-40 years were eligible. Daily intercourse records were
      used to adjust for timing and frequency of intercourse when estimating the per
      menstrual-cycle probability of conception. The number of menstrual cycles
      required to conceive a clinical pregnancy and the probability of sterility and
      infertility were derived from the estimated fecundability distributions for men
      and women of different ages. RESULTS: Sterility was estimated at about 1%; this
      percent did not change with age. The percentage infertility was estimated at 8%
      for women aged 19-26 years, 13-14% for women aged 27-34 years and 18% for women
      aged 35-39 years. Starting in the late 30s, male age was an important factor,
      with the percentage failing to conceive within 12 cycles increasing from an
      estimated 18-28% between ages 35 and 40 years. The estimated percentage of
      infertile couples that would be able to conceive after an additional 12 cycles of
      trying varied from 43-63% depending on age. CONCLUSION: Increased infertility in
      older couples is attributable primarily to declines in fertility rates rather
      than to absolute sterility. Many infertile couples will conceive if they try for
      an additional year.

PMID- 14704245
TI  - Complications of term pregnancies beyond 37 weeks of gestation.
AB  - OBJECTIVE: To estimate when rates of pregnancy complications increase beyond 37
      weeks of gestation. METHODS: We designed a retrospective, cohort study of all
      women delivered beyond 37 weeks of gestational age from 1992 to 2002 at a single
      community hospital. Rates of perinatal complications by gestational age were
      analyzed with both bivariate and multivariable analyses. Statistical significance
      was designated by P <.05. RESULTS: Among the 45673 women who delivered at 37
      completed weeks and beyond, the rates of meconium and macrosomia increased beyond
      38 weeks of gestation (P <.001), the rates of operative vaginal delivery,
      chorioamnionitis, and endomyometritis all increased beyond 40 weeks of gestation
      (P <.001), and rates of intrauterine fetal death and cesarean delivery increased
      beyond 41 weeks of gestation (P <.001). CONCLUSION: Risks to both mother and
      infant increase as pregnancy progresses beyond 40 weeks of gestation.

PMID- 14704246
TI  - Perinatal mortality in first- and second-born twins in the United States.
AB  - OBJECTIVE: To evaluate the prevailing mortality paradox that second-born twins
      are at higher risk of perinatal mortality than first-born twins. METHODS: We used
      the 1995-1997 United States "matched multiple birth" data files assembled by the
      National Center for Health Statistics, for analysis of risk of perinatal
      mortality in first- and second-born twins (293788 fetuses). Perinatal mortality
      was defined to include stillbirths after 20 weeks of gestation and neonatal
      deaths (deaths within the first 28 days). Gestational age-specific risk of
      perinatal mortality (per 1000 total births), stillbirth (per 1000 total births),
      and neonatal mortality (per 1000 livebirths) by order of twin birth were based on
      the fetuses-at-risk approach. Associations between order of birth and mortality
      indices were evaluated by fitting multivariable logistic regression models based
      on the method of generalized estimating equations. These models were adjusted for
      several potential confounding factors. RESULTS: Perinatal mortality was 37%
      higher in second-born (26.1 per 1000 total births) than in first-born (20.3 per
      1000 total births) twins (adjusted relative risk [RR] 1.37; 95% confidence
      interval [CI] 1.32, 1.42). The increased risk of perinatal mortality in second
      born twins was chiefly driven by a 2.46-fold (95% CI 2.29, 2.63) increase in the
      number of stillbirths. However, the risk of neonatal mortality was very similar
      between first- and second-born twins (RR 0.99, 95% CI 0.95, 1.04). CONCLUSIONS:
      The increased risk of perinatal death in second-born twins is driven chiefly by
      increased rates of stillborn second twins. Thus, the increased mortality in
      second-born over first-born twins probably is an artifact of mortality
      comparisons.

PMID- 14704247
TI  - Is discordant growth in twins an independent risk factor for adverse neonatal
      outcome?
AB  - OBJECTIVE: To estimate whether discordant growth is associated with adverse
      perinatal outcomes in twins after adjusting for growth restriction. METHODS: This
      was a retrospective, hospital-based cohort study of twin gestations with 2 live
      births delivered at 24 weeks or later from 1992 to 2001. Twin gestations were
      classified as small for gestational age (SGA) if one or both infants was less
      than the 10th percentile at birth by singleton Brenner norms and discordant if
      there was a 20% or more weight discordance. RESULTS: Of 1318 twin pairs, 856 were
      appropriate for gestational age (AGA) and concordant, 70 pairs were AGA and
      discordant, 254 pairs were SGA and concordant, and 138 pairs were SGA and
      discordant. The 4 groups had similar maternal demographics and medical
      comorbidity. When adjusting for chorionicity, antenatal steroid use,
      oligohydramnios, preeclampsia, and gestational age at delivery, discordant twins
      were more likely to have a cesarean delivery (odds ratio 1.87; 95% confidence
      interval 1.22, 2.87) and to be associated with some adverse neonatal outcomes
      (low and very low birthweight, neonatal intensive care unit admission, neonatal
      oxygen requirement and hyperbilirubinemia) independent of SGA status. A
      statistically nonsignificant trend (odds ratio 2.4; 95% confidence interval 0.99,
      6.01) toward higher rates of intraventricular hemorrhage was noted in discordant
      twins, and no difference was seen for ventilator requirement, respiratory
      distress syndrome, or necrotizing enterocolitis. CONCLUSION: Discordance places
      twins at increased risk for some adverse perinatal outcomes, whether they are AGA
      or SGA. Discordance was not an independent risk factor for serious neonatal
      morbidity or mortality; however, this study was underpowered to detect those
      differences.

PMID- 14704248
TI  - Second-trimester asynchronous multifetal delivery results in poor perinatal
      outcome.
AB  - OBJECTIVE: The purpose of this study is to estimate the maternal and fetal
      morbidities associated with asynchronous delivery. METHODS: A review of maternal
      and fetal medical records was performed at 2 tertiary care centers over 12 years.
      Charts were identified by the International Classification of Diseases, 9th
      Revision, Clinical Modification codes for twin and triplet gestations.
      Asynchronous delivery was defined as an active attempt (tocolysis and/or emergent
      cerclage placement) to increase latency between delivery of the first fetus and
      subsequent fetuses. RESULTS: Fourteen cases of asynchronous delivery were
      identified out of 96922 deliveries including 1352 pregnancies complicated by
      multifetal gestation. The occurrence rate of asynchronous delivery was 0.14 per
      1000 births. The etiology of preterm birth of the first fetus in 12 (86%) of 14
      cases was second-trimester rupture of membranes. The mean gestational age for
      delivery of the first fetus was 21.+/- 2.0 weeks. All women received tocolysis
      and intravenous antibiotics. Two of 3 attempts at cerclage placement were
      successful. Median latency obtained was 2 days (range less than 1-70 days). There
      was 1 survival of a first born. There were 19 retained fetuses, 2 died in utero,
      10 died between birth and day 57 of life, and 7 survived (37%; 95% confidence
      interval 16%, 62%) until hospital discharge. Six of 7 survivors had major
      sequelae from prematurity. One of 19 fetuses was discharged without major
      sequelae (5%; 95% confidence interval 0%, 25%). Maternal morbidity included 2
      placental abruptions and 8 cases of infectious morbidity including 1 case of
      septic shock. CONCLUSION: Attempts at asynchronous deliveries are uncommon and
      are associated with a high rate of perinatal death. Most fetal survivors have
      significant damage from preterm birth.

PMID- 14704249
TI  - Correlation of platelet count with second-look laparotomy results and disease
      progression in patients with advanced epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the significance of preoperative platelet counts in
      advanced epithelial ovarian cancer with respect to second-look laparotomy results
      and disease progression. METHODS: We prospectively evaluated 37 consecutive
      patients with advanced epithelial ovarian cancer who underwent primary surgical
      treatment. In addition to platelet counts, all patients were evaluated with
      respect to age, gravida, parity, and stage and grade of tumor. Thirty-six
      patients had stage III, and 1 patient had stage IV disease. Optimal debulking
      (diameter of residual tumor, less than 1 cm) was performed in all patients who
      subsequently received adjuvant chemotherapy (platin-paclitaxel). According to
      second-look laparotomy and follow-up results patients were divided into 2 groups.
      The first group had negative second-look laparotomy or no evidence of disease
      during follow-up (n = 20), and the second group had positive second-look
      laparotomy or progressive disease (n = 17). Sensitivity and specificity values
      were calculated for different cutoff values of platelet counts with receiver
      operating characteristic curve analysis. RESULTS: Age, gravida, and parity were
      not significantly different compared with controls (P >.05). Mean platelet counts
      were 371 x 109/L and 446 x 109/L in the first and second groups, respectively (P
      =.03). Different cutoff values of platelet counts for the diagnosis of
      thrombocytosis were evaluated. A cutoff value of 380 x 109/L had sensitivity 77%
      and specificity 60% for recurrence, whereas a cutoff value of 400 x 109/L had
      sensitivity 59% and specificity 65%. Area under the curve (+/- standard error)
      was 0.72 +/- 0.08 (P =.026). CONCLUSION: In patients with progressive disease and
      positive second-look laparotomy, preoperative platelet counts were significantly
      higher compared with patients with no evidence of disease on follow-up.

PMID- 14704250
TI  - Risk factors for febrile morbidity after hysterectomy.
AB  - OBJECTIVE: To identify risk factors for febrile morbidity after hysterectomy for
      nonmalignant indications. METHODS: We performed a retrospective cohort study of
      686 women who had a hysterectomy between January and September 1997 by abdominal
      (n = 408), laparoscopic-assisted vaginal (n = 90), or vaginal (n = 188)
      approaches. Potential risk factors for febrile morbidity were extracted from the
      medical records. By means of multivariable logistic regression, we evaluated
      demographic, reproductive, clinical, and operative risk factors for febrile
      morbidity. RESULTS: The risk of postoperative febrile morbidity in this
      population was 14%. Only 50% of women received prophylactic antibiotics, whereas
      almost 20% received no antibiotics at all, and 30% were administered antibiotics
      after surgical incision. Risk factors for febrile morbidity after hysterectomy,
      after controlling for age, body mass index, operative time, and prophylactic
      antibiotic administration, were abdominal approach (odds ratio 2.7; 95%
      confidence interval 1.6, 4.3) and blood loss at surgery of more than 750 mL (odds
      ratio 3.5; 95% confidence interval 1.8, 6.8). CONCLUSION: Hysterectomy by
      abdominal approach and increased blood loss at the time of surgery significantly
      increase the risk of febrile morbidity. Preventive efforts should focus on
      methods to reduce postoperative febrile morbidity, including meticulous surgical
      technique and routine use and appropriate timing of prophylactic antibiotic
      therapy.

PMID- 14704251
TI  - The quality of community colposcopic practice.
AB  - OBJECTIVE: To estimate the quality of community colposcopic practice in British
      Columbia through an assessment of the degree of correlation between colposcopy,
      cytology, and histology. METHOD: We reviewed all new-patient colposcopies in
      British Columbia during 2001 by 37 gynecologists in 24 hospital-based clinics.
      RESULTS: Colposcopic impression closely mirrored the referral cytology diagnosis
      in 89.8% of cases. As with cytology-biopsy comparisons, discordant cases were
      more likely to be overestimates of disease rather than underestimates, 18.8%
      versus 1.8%. Overestimates were usually biopsy sampling errors rather than false
      positive cytology. The overall correlation between cytology and biopsy was
      considered satisfactory in 79.4% of cases. Satisfactory agreement between the
      colposcopic diagnosis and accompanying biopsies occurred in 86.8% of patients.
      Five colposcopists had performance scores below this standard. Colposcopy with a
      sensitivity of 90.3% and a specificity of 57.3% as practiced in this provincial
      program would appear to be of a satisfactory level. The rate of intraepithelial
      or invasive disease increased from 40.6% in patients with low-grade squamous
      intraepithelial changes to 91.9% in patients with suspicious or malignant
      cytology. The value of the colposcopic impression to identify disease correlated
      best with the higher the grade of disease predicted (64.6% to 92.6%). CONCLUSION:
      A measure of the colposcopic proficiency in the community can be estimated by
      comparing the level of agreement between the presenting cytology, colposcopic
      impression, and corresponding directed biopsies. The results of this study would
      indicate that 5 individuals had practice standards that were below average. An
      integrated cytology-colposcopy program facilitates the assessment and
      identification of below-average practice standards in a community.

PMID- 14704252
TI  - Manual versus electric vacuum aspiration for early first-trimester abortion: a
      controlled study of complication rates.
AB  - OBJECTIVE: Manual vacuum aspiration is an alternative to electric suction
      curettage for first-trimester elective abortion. Although many studies have
      demonstrated that manual vacuum aspiration is safer than sharp curettage for
      abortion, only a few studies have directly compared it with electric suction
      curettage. These studies proved the methods to be equally effective and
      acceptable but were too small to adequately compare safety. We compared immediate
      complication rates for abortions performed by manual and electric vacuum
      aspiration. METHODS: We conducted a retrospective cohort analysis of all women
      undergoing elective abortion at up to 10 weeks' gestation at San Francisco
      General Hospital over a 3.5-year period. A total of 1726 procedures were
      included: 1002 manual and 724 electric vacuum aspirations. Clinical data were
      collected from medical records. Rates of uterine reaspiration and other immediate
      complications occurring at our institution were compared. RESULTS: We found no
      difference in the rate of uterine reaspiration after abortions performed with the
      manual or electric suction device (2.2% versus 1.7%, respectively, P =.43). We
      had 80% statistical power to detect a 2% difference in uterine reaspiration rates
      with an microa error of.05. Overall major complication rates were 2.5% with
      manual and 2.1% with electric suction curettage, P =.56. Multivariable regression
      analyses controlling for potential confounders showed no difference in uterine
      reaspiration rates (electric odds ratio [OR] = 0.71, 95% confidence interval [CI]
      0.32, 1.6) or overall complications (electric OR = 0.81, 95% CI 0.40, 1.7).
      CONCLUSION: Manual vacuum aspiration is as safe as electric suction curettage for
      abortions at up to 10 weeks' gestation. Expanded use in an office setting might
      increase abortion access.

PMID- 14704254
TI  - Episiotomy use among residents and faculty compared with private practitioners.
AB  - OBJECTIVE: To describe trends in episiotomy use among residents, faculty, and
      private practitioners at an academic institution. METHODS: We reviewed data from
      the Magee Obstetric Medical and Infant database, containing details of every
      delivery at Magee-Womens Hospital since 1995. The study population was women who
      had spontaneous or operative vaginal delivery of a singleton, liveborn, vertex
      presenting infant, at 37 weeks or more, from 1995 to 2000 (completed data set
      years). The first delivery recorded for a patient in the database was analyzed.
      Residents and faculty were described as "academic" practitioners. Data were
      analyzed with the Fisher exact test, chi2 test for linear trend, and logistic
      regression models. RESULTS: There were 27702 women with 15190 episiotomies, for
      an episiotomy rate of 54.8%. The rate of episiotomies decreased from 59.7% to
      45.0% during the study period (P <.001). Independent risk factors for episiotomy
      included age 30 years or more, white race, higher educational status, married,
      nulliparity, and history of cesarean delivery. The strongest predictor of
      episiotomy use was practitioner type, with women attending private physicians
      having an adjusted 7-fold increased risk of episiotomy (odds ratio 7.1; 95%
      confidence interval 6.5, 7.7). Patient characteristics related to practitioner
      type included age, race, educational status, marital status, nulliparity, and
      mode of delivery (P <.001). CONCLUSION: High rates of episiotomy use were found
      among private practitioners, despite current evidence-based literature that
      supports restricted use of episiotomy.

PMID- 14704253
TI  - Inhibition of amniotic interleukin-6 and prostaglandin E2 release by ampicillin.
AB  - OBJECTIVE: To test the effect of ampicillin on amniotic interleukin-6 (IL-6) and
      prostaglandin E2 (PGE2) release. METHODS: In an in vitro study, IL-6 and PGE2
      release from amnion-like Wistar Institute Susan Hayflick cells was assayed under
      basal conditions, as well as after incubation with ampicillin. In an in vivo
      study, amniotic fluid IL-6 was assayed in a total of 212 patients submitted to
      genetic amniocentesis during the 17th week of their singleton physiological
      pregnancy. The study population was subdivided as follows: 92 patients sampled
      before ampicillin administration, 70 patients sampled 4 hours after
      administration of 1 g ampicillin, and 50 patients sampled 12 hours after
      administration of 1 g ampicillin. RESULTS: At doses ranging from 10-7 to 10-4 M,
      ampicillin decreased IL-6 release from Wistar Institute Susan Hayflick cells. The
      drug effect was already statistically significant (-30%; P <.05) at the lowest
      concentration tested (10-7 M), reaching the maximum (-50%) at 10-6 M after 4
      hours of incubation. Moreover, ampicillin concentrations ranging from 10-7 to 10
      4 M decreased PGE2 release from Wistar Institute Susan Hayflick cells; maximal
      inhibition was reached at 10-6 M after 4 hours (-40%; P <.05). Finally, IL-6
      levels measured in amniotic fluid of patients sampled 4 hours after ampicillin
      administration proved strongly and significantly reduced when compared with those
      sampled either before or 12 hours after treatment (P <.001). CONCLUSION: The
      capacity of ampicillin to directly decrease amniotic IL-6 and PGE2 release should
      be considered in the management of bacterial and nonbacterial inflammatory
      complications of pregnancy mediated by the cytokine and prostanoid interaction.

PMID- 14704255
TI  - Risk factors and outcomes associated with a short umbilical cord.
AB  - OBJECTIVE: To identify risk factors and outcomes associated with a short
      umbilical cord. METHODS: We conducted a population-based case-control study using
      linked Washington State birth certificate-hospital discharge data for singleton
      live births from 1987 to 1998 to assess the association between maternal,
      pregnancy, delivery, and infant characteristics and short umbilical cord. Cases
      (n = 3565) were infants diagnosed with a short umbilical cord. Controls (n =
      14260) were randomly selected from among births without a diagnosis of short
      umbilical cord. RESULTS: Case mothers were less likely to be overweight (body
      mass index 25 or more, odds ratio [OR] 0.7; 95% confidence interval [CI] 0.6,
      0.8) and more likely to be primiparous (OR 1.4; 95% CI 1.3, 1.6). Case infants
      were more likely to be female (OR 1.3; 95% CI 1.2, 1.4), have a congenital
      malformation (OR 1.6; 95% CI 1.4, 1.8), and be small for their gestational age
      (risk ratio [RR] 1.6; 95% CI 1.4, 1.9). A short cord was associated with
      increased risk for maternal labor and delivery complications, including retained
      placenta (RR 1.6; 95% CI 1.2, 2.3) and operative vaginal delivery (RR 1.4; 95% CI
      1.3, 1.5). Adverse fetal and infant outcomes in cases included fetal distress (RR
      1.8; 95% CI 1.6, 2.1) and death within the first year of life among term infants
      (RR 2.4; 95% CI 1.2, 4.6). CONCLUSION: Modifiable risk factors associated with
      the development of a short cord were not identified. Case mothers and infants are
      more likely to experience labor and delivery complications. Term case infants had
      a 2-fold increased risk of death, which suggests closer postpartum monitoring of
      these infants.

PMID- 14704256
TI  - Institutional factors in cesarean delivery rates: policy and research
      implications.
AB  - OBJECTIVE: To examine the association of health care institutional
      characteristics with cesarean delivery. METHODS: Cross-sectional data from
      Taiwan's National Health Insurance database was used, covering all 270774 women
      admitted for singleton deliveries, in 2000. Bivariate and multiple logistic
      regression analyses were used. RESULTS: The overall cesarean rate was 32.3% of
      all deliveries. Obstetrics and gynecology clinics (with fewer than 10 beds) had a
      very high likelihood of cesarean delivery compared with all categories of
      hospitals (odds ratios 17-25), after adjusting for clinical complications and
      patient, physician, and institutional characteristics. The likelihood of cesarean
      delivery was similar across hospitals, regardless of level and ownership
      category. High cesarean propensity at clinics arose from higher cesarean rates in
      all complication categories, including "No complications." The overall hospital
      cesarean rate, 31.2%, is also higher than that in other developed countries with
      universal health care coverage. CONCLUSION: Taiwan has very high cesarean rates,
      with a particularly high propensity for this procedure at clinics. The cesarean
      delivery profile in the various clinical complication categories suggests a
      significantly lower clinical threshold triggering cesarean delivery decisions in
      Taiwan, especially at obstetrics and gynecology clinics. Countries currently
      having or contemplating large expansions in health insurance coverage should
      document obstetric practice profiles before initiating coverage expansions. There
      is also a need for well designed research on the medical and life-satisfaction
      impacts of cesarean compared with vaginal delivery to enable an informed policy
      stand on this issue.

PMID- 14704257
TI  - The effect of magnesium sulfate on the behavioral activities of fetal goats.
AB  - OBJECTIVES: To investigate fetal heart rate accelerations, fetal breathing
      movements, and fetal electrocortical activities during administration of
      magnesium sulfate to fetal goats. METHODS: The fetal heart rate accelerations,
      fetal breathing movements, and fetal electrocortical activities during 6 hours of
      continuous magnesium sulfate infusion into the fetal jugular vein were examined
      in 8 chronically instrumented fetal goats at 124-131 days of gestation. Fetal
      breathing movements were defined as repetitive negative fluctuations of the fetal
      tracheal pressure. Fetal electrocortical activities were assessed by visual
      analysis of periods of high-voltage and low-voltage electrocortical activities.
      RESULTS: Continuous infusion of magnesium sulfate for 6 hours significantly
      increased the fetal plasma magnesium concentration from 2.8 +/- 1.2 to 8.3 +/-
      2.6 mg/dL without significant changes in fetal arterial blood gases. The
      incidence of fetal heart rate accelerations during magnesium infusion was
      significantly decreased from that found during the control periods. After 2 hours
      of infusion, the incidence of fetal breathing movements significantly decreased
      from 33.9% +/- 20.5% to 1.2% +/- 1.4% and remained at this level during the
      remaining 4 hours of magnesium infusion. The percentage of time that the fetuses
      were found to have low-voltage electrocortical activities decreased from 51.6% +/
      9.0% to 40.4% +/- 8.2% after 2 hours of infusion but recovered to 49.9% +/-
      12.0% by 6 hours of magnesium infusion. CONCLUSION: We concluded that fetal
      magnesium sulfate administration affected fetal heart rate accelerations and
      fetal breathing movements continuously but electrocortical activities only
      temporarily during 6 hours of observations.

PMID- 14704258
TI  - The effect of board-imposed changes on maternal-fetal medicine fellowships.
AB  - OBJECTIVE: A 1996 survey of Maternal-Fetal Medicine fellows revealed that there
      was cause for serious concern over fellow experience. In 1997, Maternal-Fetal
      Medicine fellowships underwent significant changes, including a lengthening of
      the program and more stringent requirements for protected research performance.
      We investigated whether the changes imposed in Maternal-Fetal Medicine
      fellowships in 1997 have improved fellow experience. METHODS: Fellows were
      identified through the Society of Maternal-Fetal Medicine. An identical survey to
      a 1996 survey using the Likert scale, ordinal- and categorical-scale questions
      were used. The results of the 1996 survey were compared with the results of the
      2000 survey. chi2, Mann-Whitney U test, Fisher exact test, and analysis of
      variance were used where appropriate. RESULTS: Sixty-five of 100 fellows returned
      the survey (return rate, 65%). Overall, there has been improvement in many areas
      of fellow experience. Significant changes include an increase in research time (7
      months versus 18 months; P <.001), number of research projects (2.9 versus 4.3
      projects/fellow; P <.001), fellows rating research time as adequate (66.4% versus
      85.6%; P=.003), fellows receiving grant training (20.2% versus 37.1%; P=.012), 2
      or more research presentations (36.2% versus 47.1%; P=.028), pursuit of a
      postgraduate degree (5.7% versus 32.9%; P <.001), presence of a mentor (68.1%
      versus 80.8%; P=.049), and the rating of mentorship as strong (59.4% versus
      77.9%; P=.039). Of concern, 24.3% of current fellows did not believe they would
      receive their full-protected research time. CONCLUSION: The changes imposed in
      Maternal-Fetal Medicine fellowships in 1997 appear to have had a positive impact
      on fellows' experience, especially the ability to perform and present research.

PMID- 14704259
TI  - False-positive 1-hour glucose challenge test and adverse perinatal outcomes.
AB  - OBJECTIVE: To determine whether a false-positive 1-hour glucose challenge test
      (GCT) is associated with perinatal complications. METHODS: We performed a
      retrospective cohort study of 1825 eligible pregnant women among a cohort of 1998
      patients. Patients were screened for gestational diabetes mellitus (GDM) with the
      1-hour 50-g GCT at 24-28 gestational weeks. A false-positive GCT was defined as a
      result greater than or equal to 135 mg/dL followed by a normal 3-hour glucose
      tolerance test (GTT). We compared the negative GCT and false-positive GCT cohorts
      for a composite perinatal outcome variable that included fetal macrosomia,
      antenatal death, shoulder dystocia, chorioamnionitis, preeclampsia, intensive
      care nursery admission, and postpartum endometritis. Secondary outcomes included
      cesarean delivery and each component variable of the composite. Unadjusted,
      stratified, and multiple logistic regression analyses were used to investigate
      the association between a false-positive GCT and the development of perinatal
      complications. RESULTS: We identified 164 patients with a false-positive GCT and
      50 patients with GDM. The false-positive GCT cohort on average was older, of
      higher parity, had a higher body mass index, and more frequently had chronic
      hypertension, sickle cell trait, and elevated midtrimester human chorionic
      gonadotropin levels. The false-positive GCT cohort more frequently had adverse
      perinatal outcomes, including the composite perinatal outcome (odds ratio [OR]
      5.96, 95% confidence interval[CI]1.47,24.16), macrosomia greater than 4500 g (OR
      3.66, 95% CI 1.30, 10.32), antenatal death (OR 4.61, 95% CI 0.77, 27.48),
      shoulder dystocia (OR 2.85, 95% CI 1.25, 6.51), endometritis (OR 2.18, 95% CI
      1.03, 4.63), and cesarean delivery (OR 1.76, 95% CI 0.99, 3.14). CONCLUSION: A
      false-positive GCT is an independent risk factor for adverse perinatal outcomes.

PMID- 14704260
TI  - Clinical applications of cell-free fetal DNA from maternal plasma.
AB  - OBJECTIVE: To describe our clinical experience with detection and analysis of
      cell-free fetal DNA derived from maternal plasma for prenatal sexing and fetal
      rhesus-D typing. METHODS: Real-time quantitative polymerase chain reactions
      (PCRs) of rhesus-D sequences and the SRY gene were validated and offered to
      patients with an enhanced risk for sex-linked fetal pathology and patients with
      rhesus-D antibodies. RESULTS: In the validation group, 72 samples were analyzed.
      Sensitivity of the rhesus-D real-time quantitative PCR in maternal plasma was
      100% (95% confidence interval [CI]91.8%, 100%) and specificity was 96.6% (95% CI
      82.2%, 99.9%). Sensitivity of the SRY real-time quantitative PCR was 97.2% (95%
      CI 85.5%, 99.9%), and specificity was 100% (95% CI 88.1%, 100%). The technique
      was used successfully in a clinical setting in 24 women. Overall, invasive tests
      were avoided in 41.7% of these patients. CONCLUSION: Detection of cell-free fetal
      DNA from maternal plasma is a reliable technique that can substantially reduce
      invasive prenatal tests.

PMID- 14704261
TI  - Women's knowledge about treatment to prevent mother-to-child human
      immunodeficiency virus transmission.
AB  - OBJECTIVE: To provide national estimates of knowledge about treatments available
      to reduce mother-to-infant human immunodeficiency virus (HIV) transmission among
      U.S. women of childbearing age. METHODS: We used data from 55712 women aged 18 to
      44 years who responded to questions on antiretroviral treatment in the 2001
      Behavioral Risk Factor Surveillance System. We obtained the percentage of women
      who correctly answered a question on treatment to prevent mother-to-child
      transmission of HIV and determined factors independently associated with such
      knowledge using a multiple logistic regression model. RESULTS: Overall, the
      percentage of women who correctly stated that treatment existed to help prevent
      mother-to-child transmission of HIV was 58.6% (95% confidence interval 57.9,
      59.3). In the multiple logistic regression model that controlled for
      sociodemographics, having correct knowledge about treatment to prevent mother-to
      child HIV transmission was independently associated with being black, younger age
      (18-34 years), college level education, and having been tested for HIV. Current
      pregnancy was not an independent predictor of having knowledge about the
      availability of treatment to prevent mother-to-child transmission. CONCLUSION:
      Among US women of childbearing age, just over one half had correct knowledge of
      effective perinatal HIV prevention strategies. Increasing the awareness of these
      treatments may lead to greater uptake of HIV testing among pregnant women.

PMID- 14704262
TI  - Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic
      and endothelial effects.
AB  - OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal
      estrogen would be more effective than oral estrogen in reducing blood pressure
      (BP) and vascular and norepinephrine responses to stress and in increasing
      endothelial function and vascular beta2-adrenoceptor responsivity. METHODS: By
      using a randomized, double-blind, placebo-controlled design, 82 healthy
      postmenopausal smokers were tested before and after 6 months of therapy with
      transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral
      conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or
      placebo (n = 21). Dependent measures included resting and stress-induced
      increases in BP, total peripheral resistance, and plasma norepinephrine, as well
      as endothelial function and beta-adrenoceptor responsivity. RESULTS: When
      compared with placebo, the transdermal estrogen group showed more consistent
      reductions in total peripheral resistance at rest and in response to mental
      stress than the oral estrogen group. Only the transdermal group showed treatment
      related reductions in behavioral stress norepinephrine, baseline rest, and
      behavioral stress BP levels, and increases in vascular beta2-adrenoceptor
      responsivity and endothelium-dependent vasodilation. Posttreatment concentrations
      of serum estradiol and estrone were lower and the serum estradiol/estrone ratio
      closer to pre-menopausal values in the group receiving transdermal estrogen
      compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen
      therapy is associated with greater reductions in measures reflecting vascular
      sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers.
      Thus, transdermal estrogen may be associated with a more favorable risk/ benefit
      ratio in postmenopausal smokers, a group at high risk of osteoporosis and
      cardiovascular disease.

PMID- 14704263
TI  - Polycystic ovary syndrome.
AB  - Women with polycystic ovarian syndrome have chronic anovulation and androgen
      excess not attributable to another cause. This condition occurs in approximately
      4% of women. The fundamental pathophysiologic defect is unknown, but important
      characteristics include insulin resistance, hyperandrogenism, and altered
      gonadotropin dynamics. Inadequate follicle-stimulating hormone is hypothesized to
      be a proximate cause of anovulation. Obesity frequently complicates polycystic
      ovarian syndrome but is not a defining characteristic. The diagnostic approach
      should be based largely on history and physical examination, thus avoiding
      numerous laboratory tests that don't contribute to clinical management. Women
      with polycystic ovarian syndrome typically present because of irregular bleeding,
      hirsutism, and/or infertility. These conditions can be treated directly with oral
      contraceptives, oral contraceptives plus spironolactone, and ovulation induction,
      respectively. However, women with polycystic ovarian syndrome also have a
      substantially higher prevalence of diabetes and increased risk factors for
      cardiovascular disease. They should also be screened, therefore, for these
      conditions and followed closely if any risk factors are uncovered. For obese
      women with polycystic ovarian syndrome, behavioral weight management is a central
      component of the overall treatment strategy.

PMID- 14704264
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14704265
TI  - ACOG practice bulletin. Clinical management guidelines for obstetrician
      gynecologists. Number 50, January 2003.

PMID- 14704266
TI  - Single-molecule studies highlight conformational heterogeneity in the early
      folding steps of a large ribozyme.
AB  - The equilibrium folding of the catalytic domain of Bacillus subtilis RNase P RNA
      is investigated by single-molecule fluorescence resonance energy transfer (FRET).
      Previous ensemble studies of this 255-nucleotide ribozyme described the
      equilibrium folding with two transitions, U-to-I(eq)-to-N, and focused on the
      I(eq)-to-N transition. The present study focuses on the U-to-I(eq) transition.
      Comparative ensemble measurements of the ribozyme construct labeled with
      fluorescein at the 5' end and Cy3 at the 3' end show that modifications required
      for labeling do not interfere with folding and help to define the Mg(2+)
      concentration range for the U-to-I(eq) transition. Histogram analysis of the
      Mg(2+)-dependent single-molecule FRET efficiency reveals two previously
      undetermined folding intermediates. The single-molecule FRET trajectories exhibit
      non-two-state and nonergodic behaviors at intermediate Mg(2+) concentrations on
      the time scale of seconds. The trajectories at intermediate Mg(2+) concentrations
      are classified into five classes based on three FRET levels and their dynamics of
      interconversion within the measured time range. This heterogeneity, together with
      the observation of "nonsudden jump" FRET transitions, indicates that the early
      folding steps of this ribozyme involve a series of intermediates with different
      degrees of kinetic isolation and that folding occurs under kinetic control and
      involves many "local" conformational switches. A free energy contour is
      constructed to illustrate the complex folding surface.

PMID- 14704267
TI  - The origin of vibrational mode couplings in various secondary structural motifs
      of polypeptides.
AB  - Electrostatic (through-space) and covalent (through-bond) contributions to
      couplings involving the C[double bond]O and C[bond]N vibrational stretching modes
      of the amide group in the alpha-helix and the parallel and antiparallel beta
      sheet structures of alanine polypeptides are analyzed. Coupling constants
      computed at the density functional theory level are compared with the transition
      dipole coupling model and the complete electrostatic interaction between
      transition densities. We find that the transition densities of C[double bond]O
      modes are localized, and the electrostatic mechanism then holds. In contrast, the
      C[bond]N mode transition densities are delocalized, and covalent contributions to
      the coupling are significant.

PMID- 14704268
TI  - Availability of specific reductases controls the temporal activity of the
      cytochrome P450 complement of Streptomyces coelicolor A3(2).
AB  - The annotated genome of Streptomyces coelicolor A3(2) revealed 18 cytosolic
      cytochromes P450 (CYPs) with six ferredoxin (fdx) proteins and two soluble
      ferredoxin reductases (fpr), their putative electron transport proteins. mRNA
      expression was observed for all 18 CYPs throughout growth and secondary
      metabolism, from 3 h after spore germination, and all CYP proteins examined also
      were present. Expression of members of the fdx complement was detected from the
      same time point, yet both fpr were detected only at 12 h. Six-hour exposure to
      dimethylbenzanthracene and benzo[a]pyrene xenobiotics resulted in the absence of
      some CYP mRNAs and expression of a specific fpr, FR2. This finding and the
      expression pattern during growth suggested that CYP activity may be regulated by
      availability of specific reductases. To test this proposal, we expressed in
      Escherichia coli and purified to homogeneity five CYPs: CYP105D5 (involved in
      xenobiotic metabolism) and CYP154A1, CYP154C1, CYP158A1, and CYP158A2 (putatively
      involved in secondary metabolism). Also the two soluble fpr (FR2 and FR3)
      proposed to shuttle electrons by means of fdx were purified, and specific
      interactions were observed so that FR2 preferentially reduced CYP105D5 (>90%
      reduction) compared with the other CYPs (>20% reduction), whereas FR3
      preferentially reduced the other CYPs (>85% reduction) compared with CYP105D5
      (>10%). Furthermore FR2 was shown to efficiently bind CYP105D5 and drive
      benzo[a]pyrene hydroxylation in contrast to FR3. These data show that control of
      CYP activity in S. coelicolor A3(2) involves specific interactions with fpr and
      their availability during the life cycle and, after xenobiotic exposure,
      represents a unique mechanism for regulating CYP function.

PMID- 14704269
TI  - The second extracellular loop of the dopamine D2 receptor lines the binding-site
      crevice.
AB  - The binding site of the dopamine D(2) receptor (D2R), like those of homologous
      rhodopsin-like G protein-coupled receptors (GPCRs) that bind small molecules, is
      contained within a water-accessible crevice formed among its seven transmembrane
      segments (TMs). The high-resolution structure of bovine rhodopsin, however,
      revealed that the second extracellular loop (E2), which connects TM4 and TM5,
      folds down into the transmembrane domain and forms part of the ligand-binding
      surface for retinal. Whether E2 plays a related role in other rhodopsin-like
      GPCRs is unclear. To address this issue, we have now mutated to cysteine, one at
      a time, 10 consecutive residues in E2 of D2R. The reaction of five of these
      mutants with sulfhydryl reagents inhibited antagonist binding, and bound
      antagonist protected two, I184C and N186C, from reaction. The pattern of
      accessibility in E2 is consistent with a structure similar to that of bovine
      rhodopsin, in which the region C-terminal to the conserved disulfide bond is
      deeper in the binding-site crevice than is the N-terminal part of E2. Thus, E2
      likely contributes to the binding site in the D2R and probably in other aminergic
      GPCRs as well. Knowledge of its detailed positioning and interactions with ligand
      would benefit GPCR molecular modeling and facilitate the design of novel drugs.

PMID- 14704270
TI  - Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses.
AB  - Synaptojanin 1 is a polyphosphoinositide phosphatase concentrated in presynaptic
      nerve terminals, where it dephosphorylates a pool of phosphatidylinositol 4,5
      bisphosphate implicated in synaptic vesicle recycling. Like other proteins with a
      role in endocytosis, synaptojanin 1 undergoes constitutive phosphorylation in
      resting synapses and stimulation-dependent dephosphorylation by calcineurin.
      Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates synaptojanin 1
      and regulates its function both in vitro and in intact synaptosomes. Cdk5
      phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1,
      whereas dephosphorylation by calcineurin stimulated such activity. The activity
      of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its
      major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144,
      which is adjacent to the endophilin binding site. Mutation of serine 1144 to
      aspartic acid to mimic phosphorylation by Cdk5 inhibited the interaction of
      synaptojanin 1 with endophilin 1. These results suggest that Cdk5 and calcineurin
      may have an antagonistic role in the regulation of synaptojanin 1 recruitment and
      activity, and therefore in the regulation of phosphatidylinositol 4,5
      bisphosphate turnover at synapses.

PMID- 14704271
TI  - Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed
      by PSF: effects on steroidogenesis and oncogenesis.
AB  - We describe a mechanism of gene regulation involving formation of a complex
      between PSF protein and mouse VL30 (mVL30) retrotransposon RNA. PSF represses
      transcription of the insulin-like growth factor 1 (IGF1)-inducible gene P450scc
      by binding to an insulin-like growth factor response element (IGFRE) motif in the
      gene. The complex with mVL30 RNA releases PSF, allowing transcription to proceed.
      Retrovirally mediated transmission of mVL30 RNA to human tumor cells induced
      several genes, including oncogenes, which also are induced by IGF1, and promoted
      metastasis. In mice, steroid synthesis is activated in steroidogenic cells by
      pituitary hormones, which concomitantly induce transcription of mVL30 RNA in the
      cells. We showed that steroid synthesis could also be activated in mouse
      steroidogenic adrenal cells by transfection with cDNA encoding either mVL30 RNA
      tracts that form a complex with PSF or a small interfering RNA (siRNA) that
      degrades PSF transcripts. These results suggest that mVL30 RNA regulates
      steroidogenesis, and possibly other physiological processes of mice, by complex
      formation with PSF. Retrotransposons such as mVL30 apparently evolved not only as
      "junk" DNA but also as transcriptionally active noncoding DNA that acquired
      physiological and pathological functions.

PMID- 14704272
TI  - RF2b, a rice bZIP transcription activator, interacts with RF2a and is involved in
      symptom development of rice tungro disease.
AB  - The phloem-specific promoter of rice tungro bacilliform virus (RTBV) is regulated
      in part by sequence-specific DNA-binding proteins that bind to Box II, an
      essential cis element. Previous studies demonstrated that the bZIP protein RF2a
      is involved in transcriptional regulation of the RTBV promoter. Here we report
      the identification and functional characterization of a second bZIP protein,
      RF2b. RF2b, identified by its interaction with RF2a, binds to Box II in in vitro
      assays as a homodimer and as RF2a/RF2b heterodimers. Like RF2a, RF2b activates
      the RTBV promoter in transient assays and in transgenic tobacco plants. Both RF2a
      and RF2b are predominantly expressed in vascular tissues. However, RF2a and RF2b
      have different DNA-binding affinities to Box II, show distinctive expression
      patterns in different rice organs, and exhibit different patterns of subcellular
      localization. Furthermore, transgenic rice plants with reduced levels of RF2b
      exhibit a disease-like phenotype. We propose that the regulation of phloem
      specific expression of the RTBV promoter and potentially the control of RTBV
      replication are mainly achieved via interactions of the Box II cis element with
      multiple host factors, including RF2a and RF2b. We also propose that
      quenching/titration of these and perhaps other transcription factors by RTBV is
      involved in the development of the symptoms of rice tungro disease.

PMID- 14704273
TI  - Functional expression in frog oocytes of human rho 1 receptors produced in
      Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae was engineered to express the rho 1 subunit of
      the human gamma-aminobutyric acid rho 1 (GABA rho 1) receptor. RNA that was
      isolated from several transformed yeast strains produced fully functional GABA
      receptors in Xenopus oocytes. The GABA currents elicited in the oocytes were
      fast, nondesensitizing chloride currents; and the order of agonist potency was
      GABA > beta-alanine > glycine. Moreover, the receptors were resistant to
      bicuculline, strongly antagonized by (1,2,5,6 tetrahydropyridine-4
      yl)methylphosphinic acid, and modulated by zinc and lanthanum. Thus, the GABA
      receptors expressed by the yeast mRNA retained all of the principal
      characteristics of receptors expressed by cRNA or native retina mRNAs. Western
      blot assays showed immunoreactivity in yeast plasma membrane preparations, and a
      rho 1-GFP fusion gene showed mostly intracellular distribution with a faint
      fluorescence toward the plasma membrane. In situ immunodetection of rho 1 in
      yeast demonstrated that some receptors reach the plasma membrane. Furthermore,
      microtransplantation of yeast plasma membranes to frog oocytes resulted in the
      incorporation of a small number of functional yeast rho 1 receptors into the
      oocyte plasma membrane. These results show that yeast may be useful to produce
      complete functional ionotropic receptors suitable for structural analysis.

PMID- 14704274
TI  - Myc-interacting protein 1 target gene profile: a link to microtubules,
      extracellular signal-regulated kinase, and cell growth.
AB  - To study the role of the transcription factor Myc-interacting protein 1 (MIZ-1)
      in activating various target genes after induction with the microtubule
      disrupting agent T113242, we have used small interfering RNA duplexes (siRNAs) to
      knockdown the expression of MIZ-1. As expected, depletion of MIZ-1 resulted in
      the inhibition of T113242-dependent activation of the low-density lipoprotein
      receptor (LDLR) gene in hepatocytes. Cells transfected with MIZ-1 siRNAs also
      exhibited growth arrest. In addition, inhibition of the extracellular signal
      regulated kinase (ERK) pathway inhibited T113242-induced nuclear accumulation of
      MIZ-1 and activation of LDLR. Gene expression microarray analysis under various
      induction conditions identified other T113242-activated genes affected by a
      decrease in MIZ-1 and inhibition of the ERK pathway. We also found that the
      accumulation of MIZ-1 in the nucleus is influenced by cell-cell contact and/or
      growth. Taken together, our studies suggest that MIZ-1 regulates a specific set
      of genes that includes LDLR and that the ERK pathway plays a role in the
      activation of target promoters by MIZ-1.

PMID- 14704275
TI  - NADH augments blood flow in physiologically activated retina and visual cortex.
AB  - The mechanism(s) that increase retinal and visual cortex blood flows in response
      to visual stimulation are poorly understood. We tested the hypothesis that
      increased transfer of electrons and protons from glucose to cytosolic free
      NAD(+), reducing it to NADH, evoked by increased energy metabolism, fuels redox
      signaling pathways that augment flow. The near-equilibrium between free cytosolic
      NADH/NAD(+) and lactate/pyruvate ratios established by lactate dehydrogenase
      predicts that transfer of additional electrons and protons from injected lactate
      to NAD(+) will augment the elevated blood flows in stimulated retina and cortex,
      whereas transfer of electrons and protons from NADH to injected pyruvate will
      attenuate the elevated flows. These predictions were tested and confirmed in
      rats. Increased flows evoked by stimulation also were prevented by inhibition of
      nitric oxide synthase. These findings support an important role for cytosolic
      free NADH in fueling a signaling cascade that increases *NO production, which
      augments blood flow in photostimulated retina and visual cortex.

PMID- 14704276
TI  - Increased lactate/pyruvate ratio augments blood flow in physiologically activated
      human brain.
AB  - The factors regulating cerebral blood flow (CBF) changes in physiological
      activation remain the subject of great interest and debate. Recent experimental
      studies suggest that an increase in cytosolic NADH mediates increased blood flow
      in the working brain. Lactate injection should elevate NADH levels by increasing
      the lactate/pyruvate ratio, which is in near equilibrium with the NADH/NAD(+)
      ratio. We studied CBF responses to bolus lactate injection at rest and in visual
      stimulation by using positron-emission tomography in seven healthy volunteers.
      Bolus lactate injection augmented the CBF response to visual stimulation by 38
      53% in regions of the visual cortex but had no effect on the resting CBF or the
      whole-brain CBF. These lactate-induced CBF increases correlated with elevations
      in plasma lactate/pyruvate ratios and in plasma lactate levels but not with
      plasma pyruvate levels. Our observations support the hypothesis that an increase
      in the NADH/NAD(+) ratio activates signaling pathways to selectively increase CBF
      in the physiologically stimulated brain regions.

PMID- 14704277
TI  - JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a
      mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of
      dopamine-containing neurons, but the molecular pathways underlying its
      pathogenesis remain uncertain. Here, we show that by eliminating c-Jun N-terminal
      kinases (JNKs) we can prevent neurodegeneration and improve motor function in an
      animal model of PD. First, we found that c-Jun is activated in dopaminergic
      neurons from PD patients and in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine
      (MPTP) mouse model of PD. Examination of various JNK-deficient mice shows that
      both JNK2 and JNK3, but not JNK1, are required for MPTP-induced c-Jun activation
      and dopaminergic cell demise. Furthermore, we have identified cyclooxygenase
      (COX) 2 as a molecular target of JNK activation and demonstrated that COX-2 is
      indispensable for MPTP-induced dopaminergic cell death. Our data revealed that
      JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for
      neurodegeneration in PD.

PMID- 14704278
TI  - Conditional targeting of E-cadherin in skin: insights into hyperproliferative and
      degenerative responses.
AB  - Loss of E-cadherin has been associated with human cancers, and yet in the early
      mouse embryo and the lactating mammary gland, the E-cadherin null state results
      in tissue dysfunction and cell death. Here we targeted loss of E-cadherin in skin
      epithelium. The epidermal basal layer responded by elevating P-cadherin, enabling
      these cells to maintain adherens junctions. Suprabasal layers upregulated
      desmosomal cadherins, but without classical cadherins, terminal differentiation
      was impaired. Progressive hyperplasia developed with age, a possible consequence
      of proliferative maintenance in basal cells coupled with defects in terminal
      differentiation. In contrast, hair follicles lost integrity of the inner root
      sheath and hair cuticle without apparent elevation of cadherins. These findings
      suggest that, if no compensatory mechanisms exist, E-cadherin loss may be
      incompatible with epithelial tissue survival, whereas partial compensation can
      result in alterations in differentiation and proliferation.

PMID- 14704279
TI  - Identification of Lhp1p-associated RNAs by microarray analysis in Saccharomyces
      cerevisiae reveals association with coding and noncoding RNAs.
AB  - La is a conserved eukaryotic RNA-binding protein best known for its role in the
      biogenesis of noncoding RNAs transcribed by RNA polymerase III. To broaden our
      understanding of the function of the La homologous protein (Lhp1) in
      Saccharomyces cerevisiae, we have taken a genomics approach. Lhp1
      ribonucleoprotein complexes were immunoprecipitated and bound RNAs were examined
      by hybridization to whole-genome microarrays that include >6,000 ORFs, documented
      noncoding RNAs, and the intervening intergenic regions. Demonstrating the
      validity of this approach, associations with previously known Lhp1p-associated
      RNAs were detected and associations with additional noncoding RNAs, including
      multiple tRNAs and small nucleolar RNAs, were revealed. Indicating that this
      approach provides a robust method for discovering RNAs, the data also identify
      associations between Lhp1p and several intergenic regions, three of which encode
      the recently annotated putative snoRNAs: RUF1, RUF2, and RUF3. Unexpectedly, we
      find that Lhp1p is also associated with a subset of coding mRNAs. These mRNAs
      include many ribosomal protein transcripts as well as the mRNA encoding Hac1p, a
      transcription factor required during the unfolded protein stress response. In
      cells lacking LHP1, Hac1p levels are decreased 2- to 3-fold, whereas no changes
      are detected in the levels of spliced or unspliced HAC1 mRNA or in the stability
      of Hac1p. Finally, although LHP1 is dispensable for growth under standard
      conditions, we find that it is required when the unfolded protein response is
      induced at elevated temperatures. These results suggest that Lhp1p may play a
      novel role in the translation of one or more cellular mRNAs.

PMID- 14704280
TI  - Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation,
      and loss of heterozygosity analyses of 37 cell lines.
AB  - Expression of the homeobox protein CDX1 is lost or reduced in a significant
      proportion of colorectal carcinomas (CRCs) but the underlying mechanism for this
      is unclear. We have demonstrated absence of CDX1 mRNA expression in 7 of 37 CRC
      cell lines and shown that all 7 cell lines have a methylated CDX1 promoter.
      Twenty-five cell lines showed both CDX1 mRNA expression and an unmethylated CDX1
      promoter. The five remaining cell lines had a partially methylated CDX1 promoter
      and all expressed CDX1 mRNA; when treated with the demethylating agent, 5-aza-2'
      deoxycytidine, these five cell lines all showed increased CDX1 expression. No
      mutations were found in the promoter and coding regions of CDX1. One polymorphism
      was demonstrated in each of the promoter, 5' UTR, and coding region of exon 1 of
      CDX1, but there were no associations between CDX1 mRNA expression and different
      polymorphic genotypes. Similarly, there was no association between CDX1 mRNA
      expression and loss of heterozygosity at the CDX1 locus. In conclusion, absence
      or reduction of CDX1 expression in CRC seems to be primarily regulated by
      promoter methylation and is probably selected for because of its impact on the
      differentiation of colonocytes.

PMID- 14704282
TI  - Design of genetic networks with specified functions by evolution in silico.
AB  - Recent studies have provided insights into the modular structure of genetic
      regulatory networks and emphasized the interest of quantitative functional
      descriptions. Here, to provide a priori knowledge of the structure of functional
      modules, we describe an evolutionary procedure in silico that creates small gene
      networks performing basic tasks. We used it to create networks functioning as
      bistable switches or oscillators. The obtained circuits provide a variety of
      functional designs, demonstrate the crucial role of posttranscriptional
      interactions, and highlight design principles also found in known biological
      networks. The procedure should prove helpful as a way to understand and create
      small functional modules with diverse functions as well as to analyze large
      networks.

PMID- 14704281
TI  - Electrocardiographic and other cardiac anomalies in beta-glucuronidase-null mice
      corrected by nonablative neonatal marrow transplantation.
AB  - Cardiovascular manifestations of lysosomal storage disease (LSD) are a
      significant health problem for affected patients. Infantile-onset cardiac
      disease, because of its rapid progression, is usually treated symptomatically.
      Therapy in older patients includes valve replacement and bone marrow (BM)
      transplantation, both of which are life threatening in the already debilitated
      patients. Enzyme replacement therapy has potential benefit but has not yet been
      demonstrated to provide long-term relief for cardiac disease. Here, we
      demonstrate prevention of severe cardiac manifestations in beta-glucuronidase
      (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative
      pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly
      syndrome), develop progressive LSD unless provided with GUSB early in life. The
      BM recipients retained GUSB+ donor cells in the peripheral blood and heart until
      necropsy at > or = 11 months of age. The enzyme beta-hexosamindase increased in
      tissues of GUSB null MPSVII mice was reduced significantly (P = 0.001) in treated
      MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR,
      PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the
      stroma of heart valves, adventitial cells of the aortic root, perivascular and
      interstitial cells of the myocardium, and interstitial cells of the conduction
      tissue. Heart/body weight ratio normalized. The aortic root was still grossly
      distended, and the conductive myocytes retained storage, suggesting neither plays
      a major role in ECG normalization. We conclude that transplantation of MPSVII
      neonates without toxic intervention can prevent many of the cardiovascular
      manifestations of LSD.

PMID- 14704283
TI  - Organic light-emitting diodes formed by soft contact lamination.
AB  - Although tremendous progress has been made in organic light-emitting diodes
      (OLEDs), with few exceptions they are fabricated in the standard way by
      sequentially depositing active layers and electrodes onto a substrate. Here we
      describe a different approach for building OLEDs, which is based on physical
      lamination of thin metal electrodes supported by an elastomeric layer against an
      electroluminescent organic. This method relies only on van der Waals interactions
      to establish spatially homogeneous, intimate contacts between the electrodes and
      the organic. We find that devices fabricated in this manner have better
      performance than those constructed with standard processing techniques. The
      lamination approach avoids forms of disruption that can be introduced at the
      electrode/organic interface by metal evaporation and has a reduced sensitivity to
      pinhole or partial pinhole defects. In addition, because this form of "soft"
      contact lamination is intrinsically compatible with the techniques of soft
      lithography, it is easy to build patterned OLEDs with feature sizes into the
      nanometer regime. This method provides a new route to OLEDs for applications
      ranging from high performance displays to storage and lithography systems that
      rely on subwavelength light sources.

PMID- 14704284
TI  - Hepcidin, the recently identified peptide that appears to regulate iron
      absorption.
AB  - A newly identified iron regulator, hepcidin, appears to communicate body iron
      status and demand for erythropoiesis to the intestine, and in turn, modulates
      intestinal iron absorption. Hepcidin was first purified from human blood and
      urine as an antimicrobial peptide and was found to be predominantly expressed in
      the liver. A lack of hepcidin expression has been associated with iron overload
      and overexpression of hepcidin results in iron-deficiency anemia in mice. In
      addition, hepcidin levels decrease in mice fed a low iron diet and increase in
      mice fed a high iron diet. These observations support the role of hepcidin as a
      signal that limits intestinal iron absorption. Hepcidin expression is also
      affected by hypoxia and inflammation and is decreased in hemochromatosis
      patients. Thus, the relationship between body iron status and hepcidin is altered
      in hemochromatosis patients. In addition, hepcidin is decreased in HFE knockout
      mice, which demonstrates characteristics of iron overload as in hemochromatosis
      patients. Hence, HFE is suggested to act as a regulator of hepcidin expression.
      Transcription factors, such as C/EBPalpha, are also suggested to be involved in
      the regulation of hepcidin gene expression. However, much remains to be
      investigated in the regulation of hepcidin by iron, hypoxia and inflammation.

PMID- 14704285
TI  - Dietary resveratrol does not affect intestinal tumorigenesis in Apc(Min/+) mice.
AB  - To determine its effect on intestinal tumorigenesis and the protumorigenic COX
      pathway in Apc(Min/+) mice, resveratrol was administered as a powdered admixture
      in the diet at 0, 4, 20, or 90 mg/kg body weight for 7 wk. In two separate
      experiments, resveratrol did not affect intestinal tumor load. It was stable in
      the diet under experimental conditions, circulated in the plasma as the
      glucuronide-conjugated form and reached the tumors as evidenced by significant
      decreases in PGE2 levels. However, immunohistochemical staining of intestinal
      tumors revealed no changes in COX-2 expression. This study demonstrates that
      resveratrol consumed ad libitum in the diet, does not modify tumorigenesis in
      Apc(Min/+) mice.

PMID- 14704286
TI  - An energy-rich diet causes rumen papillae proliferation associated with more IGF
      type 1 receptors and increased plasma IGF-1 concentrations in young goats.
AB  - We tested the hypothesis that the dietary energy-dependent alterations of the
      rumen papillae size are accompanied by corresponding changes in systemic insulin
      like growth factor (IGF)-1 concentration and in rumen papillary IGF type 1
      receptors (IGF-1R). Young male goats (n=24) were randomly allocated to two groups
      (n=12) and fed a high level (HL) metabolizable energy [1200 kJ/(kg(0.75).d)] or a
      low level (LL) [500 kJ/(kg(0.75).d)] diet for 42 d. The concentration of ruminal
      total SCFA did not differ between the groups, but the molar proportion of butyric
      acid was enhanced by 70% in the HL group (P<0.05). Both the length and width of
      the papillae were greater (P<0.05) in the HL group, and the surface was 50-100%
      larger (P<0.05) in the tissue sampled from the artrium ruminis, the ventral
      ruminal sac and the ventral blind sac. Transport of Na+ across the rumen
      epithelium, which is amiloride sensitive, was higher (P<0.05) in the HL than in
      the LL group. Furthermore, the plasma IGF-1 concentration was about twofold
      higher in the HL group (P<0.05), and the maximal rumen epithelial IGF-1R binding
      was also higher in the HL (P<0.05) than in the LL group. IGF-1R mRNA and IGF-1
      mRNA were detected in rumen papillae; however, they were unaffected by dietary
      treatments. DNA synthesis and cell proliferation of cultured rumen epithelial
      cells were higher (P<0.05) after IGF-1 treatment (25 or 50 microg/L) compared
      with those in the medium without IGF-1. Thus dietary energy-dependent alterations
      of rumen morphology and function are accompanied by corresponding changes in
      systemic IGF-1 and ruminal IGF-1R.

PMID- 14704287
TI  - Proteins of white lupin seed, a naturally isoflavone-poor legume, reduce
      cholesterolemia in rats and increase LDL receptor activity in HepG2 cells.
AB  - White lupin (Lupinus albus, L.), a widely cultivated crop that has been consumed
      for many years in Western Europe, may provide a useful alternative for
      individuals wishing to substitute animal with plant proteins for cardiovascular
      disease prevention. Lupin seeds have a very low content of isoflavones, and lupin
      protein isolates are essentially isoflavone free. In rats fed a casein-based
      cholesterol + cholic acid diet, a relatively low daily intake (50 mg/d by gavage
      for 2 wk) of total lupin protein extract reduced plasma total and VLDL + LDL
      cholesterol concentrations by 21 and 30%, respectively (both P<0.001). In an
      attempt to elucidate the lipid-lowering mechanism, LDL receptor activity was
      evaluated in a human hepatoma cell line (HepG2). In this model, the lupin total
      protein extract was essentially inactive, whereas one purified minor protein
      component, conglutin gamma, had a remarkable upregulatory effect, with maximal
      increases of 53 and 21% (both P<0.05) for LDL uptake and degradation,
      respectively. This initial study indicates that lupin, although isoflavone free,
      has hypocholesterolemic activity similar to that of other leguminous proteins in
      an established animal model. Further, the cholesterol reduction appears to be
      associated with stimulation of LDL receptors by a well-defined protein component
      of the lupin seeds as demonstrated by in vitro studies.

PMID- 14704288
TI  - Amino acids do not alter the insulin-induced activation of the insulin signaling
      pathway in neonatal pigs.
AB  - Feeding stimulates protein synthesis in skeletal muscle and liver of neonates and
      this response can be reproduced in muscle by the infusion of insulin or amino
      acids and in liver by the infusion of amino acids, but not insulin. Activation of
      insulin signaling components leading to translation initiation is associated with
      the feeding-induced stimulation of muscle protein synthesis in neonates. In this
      study, we examined the individual roles of insulin and amino acids in the
      activation of insulin signaling components leading to translation initiation,
      specifically, the insulin receptor (IR), insulin receptor substrate 1 (IRS-1),
      phosphatidylinositol 3-kinase (PI 3-kinase), protein kinase B (PKB) and ribosomal
      protein S6. Insulin secretion was blocked by somatostatin in food-deprived, 7-d
      old pigs (n=8-12/group); insulin was infused to achieve plasma levels of
      approximately 0, 17, 52, and 255 pmol/L (approximately 0, 2, 6, 30 microU/mL),
      and amino acids were clamped at food-deprived or fed levels. In skeletal muscle,
      insulin increased the activation of IR, IRS-1, PI 3-kinase, PKB and S6 and
      stimulated protein synthesis. In liver, insulin increased the activation of IR,
      IRS-1, PI 3-kinase, PKB and S6, but had no effect on protein synthesis. Raising
      amino acids from the food-deprived to the fed level did not alter the insulin
      induced activation of IR, IRS-1, PI 3-kinase and PKB but increased S6
      phosphorylation and protein synthesis in skeletal muscle and liver. The results
      suggest that the stimulation of protein synthesis in muscle by insulin involves
      activation of insulin signaling components, and the stimulation of protein
      synthesis in muscle and liver by amino acids occurs by mechanisms independent of
      the early steps of this pathway. Furthermore, amino acids do not alter the
      insulin-stimulated activation of early steps in the insulin signaling pathway.

PMID- 14704289
TI  - The binding of folic acid and 5-methyltetrahydrofolate to folate-binding proteins
      during gastric passage differs in a dynamic in vitro gastrointestinal model.
AB  - Despite its low natural folate concentration, milk is responsible for 10-15% of
      the daily folate intake in countries with a high dairy consumption. Milk products
      can be considered as a potential matrix for folate fortification, e.g., with
      synthetic folic acid, to enhance the daily intake of folate. In untreated milk,
      the natural folate, 5-methyltetrahydrofolate (5-CH3-H4folate), is bound to folate
      binding proteins (FBP). In this study, the extent of binding to FBP for folic
      acid and 5-CH3-H4folate was investigated in a dynamic in vitro model simulating
      human gastric passage. Protein binding of folic acid and 5-CH3-H4folate was
      characterized using gel-exclusion chromatography. Before gastric passage, folic
      acid and 5-CH3-H4folate were bound mainly to FBP (76-79%), whereas 7% was free.
      Folic acid remained bound to FBP to a similar extent after gastric passage. For 5
      CH3-H4folate, the FBP-bound fraction gradually decreased from 79 to 5% and the
      free fraction increased from 7 to 93%. Although folic acid enters the proximal
      part of the intestine bound to FBP, 5-CH3-H4folate appears to be present mainly
      as free folate in the duodenal lumen. The stability of FBP was similar in both
      folate/FBP mixtures, i.e., 70% of the initial FBP content was retained after
      gastric passage. This study indicated that FBP are partly stable during gastric
      passage but have different binding characteristics for folic acid and 5-CH3
      H4folate in the duodenal lumen. This could result in different bioavailability
      from folic acid- and 5-CH3-H4folate-fortified milk products.

PMID- 14704290
TI  - Black and green tea polyphenols attenuate blood pressure increases in stroke
      prone spontaneously hypertensive rats.
AB  - Oxidative stress was reported to be involved not only in cardiovascular diseases,
      but also in hypertension. Epidemiologic studies indicated that tea consumption
      slightly reduces blood pressure. We conducted two studies to determine whether
      black and green tea can lower blood pressure (BP) in stroke-prone spontaneously
      hypertensive rats (SHRSP). Male SHRSP (n=15) were allowed to recover for 2 wk
      after a transmitter for measuring BP was implanted in the peritoneal cavity. The
      rats were divided into three groups: the control group consumed tap water (30
      mL/d); the black tea polyphenol group (BTP) consumed water containing 3.5 g/L
      thearubigins, 0.6 g/L theaflavins, 0.5 g/L flavonols and 0.4 g/L catechins; and
      the green tea polyphenol group (GTP) consumed water containing 3.5 g/L catechins,
      0.5 g/L flavonols and 1 g/L polymetric flavonoids. The telemetry system was used
      to measure BP, which were recorded continuously every 5 min for 24 h. During the
      daytime, systolic and diastolic BP were significantly lower in the BTP and GTP
      groups than in the controls. Protein expressions of catalase and phosphorylated
      myosin light chain (MLC-p) were measured in the aorta by Western blotting. GTP
      significantly increased catalase expression, and BTP and GTP significantly
      decreased MLC-p expression in the aorta. These data demonstrate that both black
      and green tea polyphenols attenuate blood pressure increases through their
      antioxidant properties in SHRSP. Furthermore, because the amounts of polyphenols
      used in this experiment correspond to those in approximately 1 L of tea, the
      regular consumption of black and green tea may also provide some protection
      against hypertension in humans.

PMID- 14704291
TI  - Dietary protein-related changes in hepatic transcription correspond to
      modifications in hepatic protein expression in growing pigs.
AB  - In a previous investigation we showed by expression profiling based on
      transcription analysis using differential display RT-PCR (DDRT-PCR) and real-time
      RT-PCR that a soy protein diet (SPI) significantly changes the hepatic
      transcription pattern compared with a casein diet (CAS). The present study was
      conducted to determine whether the transcriptional modulation is translated into
      protein expression. The hepatic mRNA abundance of four genes (EP24.16, LC3,
      NPAP60L, RFC2) that showed diet-related expression in previous DDRT-PCR
      experiments was analyzed by real-time RT-PCR. Two pigs that showed the most
      prominent SPI-related changes of transcription and two casein-fed pigs were
      selected and their hepatic protein pattern was studied comparatively by two
      dimensional gel electrophoresis and peptide mass fingerprinting. The two
      dimensional protein gel electrophoresis revealed a predominant SPI-associated
      upregulation of protein expression that corresponded to the results of the mRNA
      study. Of 380 diet-related protein spots displayed, 215 appeared exclusively or
      enlarged in the two SPI pigs; 10 of 39 diet-related expressed protein spots
      extracted could be identified by peptide mass fingerprinting and database search.
      Compared with the transcriptomics approach, the proteomics approach led in part
      to the identification of the same diet-associated expressed molecules
      (plasminogen, trypsin, phospholipase A2, glutathione-S-transferase alpha, retinal
      binding protein) or at least molecules belonging to the same metabolic pathways
      (protein and amino acid metabolism, oxidative stress response, lipid metabolism).
      The present results at the proteome level confirm SPI-related increased oxidative
      stress response and significant effects on protein biosynthesis already observed
      at the transcriptome level.

PMID- 14704292
TI  - Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin
      are important determinants of genome stability in cultured human lymphocytes.
AB  - We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism, folic acid deficiency and riboflavin deficiency, independently or
      interactively, are important determinants of genomic stability, cell death, cell
      proliferation and homocysteine (Hcy) concentration in 9-d human lymphocyte
      cultures. Lymphocytes of seven wild-type (CC) and seven mutant (TT) homozygotes
      were cultured under the four possible combinations of deficiency and sufficiency
      of riboflavin (0 and 500 nmol/L) and folic acid (20 and 100 nmol/L) at a constant
      L-methionine concentration of 50 micromol/L. Viable cell growth was 25% greater
      in TT than in CC cells (P<0.05) and 32% greater at 100 nmol/L folic acid than at
      20 nmol/L folic acid (P=0.002). The comprehensive cytokinesis-block micronucleus
      assay was used to measure micronuclei (MNi; a marker for chromosome breakage and
      loss), nucleoplasmic bridges (NPB; a marker of chromosome rearrangement) and
      nuclear buds (NBUD, a marker of gene amplification). The MNi levels were 21%
      higher in TT cells than in CC cells (P<0.05) and 42% lower in the high folic acid
      medium than in the low folic acid medium (P<0.0001). The NBUD levels were 27%
      lower in TT cells than in CC cells (P<0.05) and 45% lower in the high folic acid
      medium than in the low folic acid medium (P<0.0001). High riboflavin
      concentration (500 nmol/L) increased NBUD levels by 25% (compared with 0 nmol/L
      riboflavin) in folate-deficient conditions (20 nmol/L folic acid medium; P<0.05),
      and there was an interaction between folic acid and riboflavin that affected NBUD
      levels (P=0.042). This preliminary investigation suggests that MTHFR C677T
      polymorphism and riboflavin affect genome instability; however, the effect is
      relatively small compared with that of folic acid.

PMID- 14704293
TI  - Identification of genes responsive to intracellular zinc depletion in the human
      colon adenocarcinoma cell line HT-29.
AB  - Zinc is essential for the structural and functional integrity of cells and plays
      a pivotal role in the control of gene expression. To identify genes with altered
      mRNA expression level after zinc depletion, we employed oligonucleotide arrays
      with approximately 10,000 targets and used the human colon adenocarcinoma
      epithelial cell line HT-29 as a model. A low intracellular zinc concentration
      caused alterations in the steady-state mRNA levels of 309 genes at a threshold
      factor of 2.0. Northern blot analysis and/or real-time RT-PCR confirmed the array
      results for 12 of 14 selected targets. Genes identified as regulated based on
      microarray data encode mainly proteins involved in central pathways of
      intermediary metabolism (79 genes) including protein metabolism (21). We also
      identified five groups of genes important for basic cellular functions such as
      signaling (30), cell cycle control and growth (15), vesicular trafficking (15),
      cell-cell interaction (13), cytoskeleton (10) and transcription control (19). The
      latter group comprises several zinc finger-containing transcription factors of
      which the Kruppel-like factor 4 showed the most pronounced changes. Western blot
      analysis confirmed the increased expression level of this protein in cells grown
      under low zinc conditions. Our findings in a homogeneous cell population
      demonstrate that the molecular mechanisms by which cellular functions are altered
      at a low zinc status, occur via pleiotropic effects on gene expression. In
      conclusion, the pattern of zinc-affected genes may represent a reference for
      further studies to define the zinc regulon in mammalian cells.

PMID- 14704294
TI  - Decreased insulin secretion in islets from rats fed a low protein diet is
      associated with a reduced PKAalpha expression.
AB  - A low protein diet has been shown to affect the amount and activity of several
      enzymes and to decrease insulin secretion by islets isolated from rats fed such a
      diet. To understand the mechanisms involved in this phenomenon, we investigated
      the effects of forskolin, a stimulator of adenylyl cyclase, on insulin secretion
      by pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein
      diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate
      solution containing 8.3 mmol glucose/L, with or without 10 micromol forskolin/L.
      The forskolin-induced insulin secretion was higher in islets from NP rats than in
      those from LP rats (P<0.05). Western blotting revealed that the amount of the
      alpha catalytic subunit of protein kinase A (PKAalpha) was 35% lower in islets
      from LP rats than in islets from NP rats (P<0.05). Moreover, PKAalpha mRNA
      expression was reduced by 30% in islets from LP rats (P<0.05). Our results
      indicated a possible relationship between a low protein diet and a reduction in
      PKAalpha expression. These alterations in PKAalpha may be responsible in part for
      the decreased insulin secretion by islets from rats fed a low protein diet.

PMID- 14704295
TI  - Conjugated linoleic acid upregulates LDL receptor gene expression in HepG2 cells.
AB  - Conjugated linoleic acid (CLA) exerts anticarcinogenic and antiatherosclerotic
      effects in animals. The present study was conducted to examine the effects of CLA
      on LDL receptor (LDLr) expression in HepG2 cells, and to evaluate whether the
      sterol response element binding protein 1 (SREBP-1) and acyl CoA:cholesterol
      acyltransferase (ACAT) were involved in the regulation of LDLr expression by CLA.
      When HepG2 cells were cultured with serum-free DMEM for 48 h, there was a three-
      to fivefold (P<0.05) increase in LDLr protein and mRNA levels. Incubation of
      HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH, 5
      mg/L) for 24 h decreased LDLr protein and mRNA by 50-70% (P<0.05) and mature
      SREBP-1 by 20-40% (P<0.05). CLA, but not linoleic acid, antagonized the
      depressive effects of 25OH and increased both LDLr protein and mRNA abundance
      twofold (P<0.05). LDLr protein and mRNA abundance were not different when HepG2
      cells were cultured with CLA (0.4 mmol/L) plus 25OH in the presence or absence of
      an ACAT inhibitor (58-035, 1 mg/L). Furthermore, CLA had no effect on SREBP-1
      abundance. These results suggest that CLA upregulates LDLr expression via a
      mechanism that is independent of ACAT and SREBP-1.

PMID- 14704296
TI  - Parenteral and enteral routes of feeding in neonatal piglets require different
      ratios of branched-chain amino acids.
AB  - The requirements for total branched-chain amino acids (BCAA), isoleucine, leucine
      and valine, in neonatal piglets receiving parenteral and enteral nutrition was
      determined recently. The optimum ratio among BCAA during different routes of
      feeding is not yet known. In this study, the ratio of BCAA during parenteral and
      enteral feeding was tested using the indicator amino acid oxidation (IAAO)
      technique. Male Yorkshire piglets (n=24) received amino acid-based diets
      containing adequate nutrients for 5 d. Phenylalanine oxidation and kinetics were
      determined from a 4-h primed, constant infusion of L-[1-14C]-phenylalanine on d 6
      and 8. On d 6, all piglets received a BCAA diet which met 75% of the total BCAA
      requirement, based on our previous research, with a ratio of 1:1.8:1.2 of
      isoleucine/leucine/valine. On d 8, the piglets were randomly assigned to receive
      one of the 3 test diets supplemented with isoleucine (+isoleucine), leucine
      (+leucine) or valine (+valine) to meet 100% of requirement, with the remaining
      two BCAA at 75% of requirement. The difference in phenylalanine oxidation (% of
      dose) between d 6 and 8 was used as an indicator of BCAA adequacy. In enterally
      fed piglets, the change in the percentage of the dose oxidized was minimal for
      all 3 test diets (mean=1.15%). In parenterally fed piglets, the difference in
      phenylalanine oxidation (% of dose) between d 6 and 8 was +isoleucine (12.6%),
      +leucine (2%) and +valine (6.6%). The ratio of 1:1.8:1.2 of
      isoleucine/leucine/valine is appropriate for enteral feeding, but during
      parenteral feeding, isoleucine was first limiting and valine was second limiting.

PMID- 14704297
TI  - Bone loss induced by dietary magnesium reduction to 10% of the nutrient
      requirement in rats is associated with increased release of substance P and tumor
      necrosis factor-alpha.
AB  - Dietary Mg intake has been linked to osteoporosis. Previous studies have
      demonstrated that severe Mg deficiency [0.04% of nutrient requirement (NR)]
      results in osteoporosis in rodent models. We assessed the effects of more
      moderate dietary Mg restriction (10% of NR) on bone and mineral metabolism over a
      6-mo experimental period in rats. At 2, 4 and 6 mo, serum Mg, Ca, parathyroid
      hormone (PTH), 1,25-dihydroxy-vitamin D, alkaline phosphatase, osteocalcin and
      urine pyridinoline were measured. Femurs and tibiae were collected for
      measurement of mineral content, microcomputerized tomography, histomorphometry,
      and immunocytochemical localization. By 2 mo, profound Mg deficiency had
      developed as assessed by marked hypomagnesemia and up to a 51% reduction in bone
      Mg content. These features continued through 6 mo of study. Serum Ca was slightly
      but significantly higher in Mg-deficient rats than in controls at all time
      points. At 2 mo, serum PTH was elevated in Mg-deficient rats but was
      significantly decreased at 6 mo in contrast to control rats in which PTH rose.
      Serum 1,25-dihydroxy-vitamin D was significantly lower than in controls at 4 and
      6 mo. A significant fall in both serum alkaline phosphatase and osteocalcin
      suggested decreased osteoblast activity. Histomorphometry demonstrated decreased
      bone volume and trabecular thickness. This was confirmed by microcomputerized
      tomography analysis, which also showed that trabecular volume, thickness and
      number were significantly lower in Mg-deficient rats. Increased bone resorption
      was suggested by an increase in osteoclast number over time compared with
      controls as well as surface of bone covered by osteoclasts and eroded surface,
      but there was no difference in osteoblast numbers. The increased bone resorption
      may be due to an increase in TNF-alpha because immunocytochemical localization of
      TNF-alpha in osteoclasts was 199% greater than in controls at 2 mo, 75% at 4 mo
      and 194% at 6 mo. The difference in TNF-alpha may be due to substance P, which
      was 250% greater than in controls in mononuclear cells at 2 mo and 266% at 4 mo.
      These data demonstrated that a Mg intake of 10% of NR in rats causes bone loss
      that may be secondary to the increased release of substance P and TNF-alpha.

PMID- 14704298
TI  - Supplementation of sows with L-carnitine during pregnancy and lactation improves
      growth of the piglets during the suckling period through increased milk
      production.
AB  - Recent studies showed that piglets of sows fed diets supplemented with L
      carnitine grow faster during the suckling period than piglets of control sows fed
      diets without L-carnitine. This study was undertaken to investigate the effect of
      L-carnitine supplementation in sows on milk production and milk constituents. An
      experiment was performed in which two groups of 20 gilts each were fed diets with
      or without supplemental L-carnitine during pregnancy (0 vs. 125 mg L-carnitine
      daily/sow) and lactation (0 vs. 250 mg L-carnitine daily/sow). The experiment was
      continued over two reproductive cycles. L-carnitine-treated sows had larger
      litters (P<0.01) and higher litter weights (P<0.05) than control sows. Piglets of
      L-carnitine-treated sows had lower birth weights (P<0.05) but grew faster during
      the suckling period (P<0.01) and were heavier (P<0.05) at weaning than piglets of
      control sows. L-carnitine-treated sows had higher milk yields on d 11 and 18 of
      lactation than control sows (P<0.05). Milk of L-carnitine-treated sows had higher
      concentrations of total and free carnitine than milk of control sows (P<0.001);
      concentrations of fat, protein and lactose and the amounts of gross energy in the
      milk did not differ between the two groups of sows. The amounts of protein
      (P<0.05) and lactose (P<0.05) were higher in L-carnitine-treated sows than in
      control sows; the amount of energy secreted with the milk tended to be higher in
      carnitine-treated sows than in control sows (P<0.10). The study suggests that
      piglets of carnitine-treated sows grow faster during the suckling period than
      those of control sows because they ingest more nutrients and energy with the
      milk.

PMID- 14704299
TI  - A low-molecular-weight factor in human milk whey promotes iron uptake by Caco-2
      cells.
AB  - The iron bioavailability of human milk (HM) is substantially greater than that of
      cow's milk (CM), but the factor responsible for this high bioavailability is
      unknown. This study evaluated the effects of various HM and CM fractions on iron
      bioavailability. Milk was separated into fat, casein and whey fractions by
      ultracentrifugation. Whey was further fractionated by ultrafiltration with a 10
      kDa membrane to produce a 10-kDa retentate (10kR) and a 10-kDa filtrate (10kF).
      Samples were prepared by mixing various combinations of the fractions, bringing
      the samples to prefractionation weight with minimum essential medium (MEM), and
      adding iron (10 micro mol/L) as ferrous sulfate. Samples were divided into two
      aliquots: one was subjected to in vitro digestion, the other was not.
      Bioavailability was assessed by applying the samples to Caco-2 cell monolayers
      and incubating for 24 h. Ferritin formation in the cells was used as an index of
      iron uptake. Removing the fat from undigested HM samples doubled the ferritin
      formation, but removing the whey or casein had no effect. Results with digested
      HM samples were similar, except that removing the whey decreased ferritin
      formation by 48%. Removing the fat from digested CM samples had no effect, but
      removing the casein doubled the ferritin formation. Removing the 10kF from HM
      reduced ferritin formation by 60%, but removing the 10kR had no effect. These
      data suggest that a low-molecular-weight factor (<10 kDa) in human milk enhances
      iron absorption.

PMID- 14704300
TI  - Iron supplementation does not affect the susceptibility of LDL to oxidative
      modification in women with low iron status.
AB  - Elevated iron stores may or may not promote atherogenesis by increasing free
      radical formation and oxidative stress, but controlled diet and supplement trials
      are lacking. We tested the hypothesis that iron supplementation does not increase
      the susceptibility of LDL to undergo oxidative modification in women with low
      iron status. A randomized, double-blind, 2-period crossover study design (n=26)
      was used to examine the effects of the following diets on measures of LDL
      oxidation: average American diet (AAD) [36% of energy as fat; 15% saturated fatty
      acids (SFA)], and a Step 2 diet (26% fat; 7% SFA). In addition, subjects received
      either a supplement containing 160 mg of ferrous sulfate (50 mg elemental iron)
      or a placebo twice daily [supplement group received a total of 320 mg ferrous
      sulfate (100 mg elemental iron) daily]. After supplementation, serum ferritin
      differed between the supplement and placebo groups (P=0.008). Measures of LDL
      oxidation were not affected by supplement intake; however, they were affected by
      diet. Lag time was shorter after the women consumed the AAD diet than after the
      Step 2 diet (P<0.0001). The diets did not affect the rate of oxidation or total
      dienes. Although iron status was improved by aggressive iron supplementation, LDL
      oxidative susceptibility was not affected. As expected, lag time was increased
      after the women consumed the low fat, low SFA diet. Therefore, the results of
      this study do not support a relationship between iron status and LDL oxidation.

PMID- 14704301
TI  - The time of day of food intake influences overall intake in humans.
AB  - Circadian and diurnal rhythms affect food intake, and earlier research has
      suggested that meal sizes increase, whereas the after-meal intervals and satiety
      ratios decrease over the day. We hypothesized that the time of day of food intake
      would be related to total intake such that intake early in the day would tend to
      reduce overall intake, whereas intake later in the day would tend to increase
      intake over the entire day. The intakes of 375 male and 492 female free-living
      individuals, previously obtained via 7-d diet diaries, were reanalyzed. The total
      and meal intakes of food energy, the amounts of the macronutrients ingested and
      the density of intake occurring during five 4-h periods (0600-0959, 1000-1359,
      1400-1759, 1800-2159 and 2200-0159 h) were identified and related to overall and
      meal intakes during the entire day. The proportion of intake in the morning was
      negatively correlated with overall intake (r=-0.13, P<0.01), whereas the
      proportion ingested late in the evening was positively correlated with overall
      intake (r=0.14, P<0.01). The energy densities of intake during all periods of the
      day were positively related to overall intake (range, r=0.13-0.23, P<0.01). The
      results suggest that low energy density intake during any portion of the day can
      reduce overall intake, that intake in the morning is particularly satiating and
      can reduce the total amount ingested for the day, and that intake in the late
      night lacks satiating value and can result in greater overall daily intake.

PMID- 14704302
TI  - Intestinal adaptation occurs independently of parenteral long-chain
      triacylglycerol and with no change in intestinal eicosanoids after mid-small
      bowel resection in rats.
AB  - The role of enteral or parenteral long-chain triacylglycerol (LCT) in the complex
      process of intestinal adaptation is poorly defined and may involve alterations in
      eicosanoid synthesis. Our objective was to determine whether provision of
      parenteral LCT stimulates eicosanoid synthesis and resection-induced intestinal
      adaptation. We assessed small bowel structural adaptation, the fatty acid
      profiles of liver, plasma and jejunal mucosa, and the profile of 11 eicosanoids
      derived from (n-6) PUFA of the jejunal mucosa in rats maintained with total
      parenteral nutrition (TPN) with 0 or 32% of nonprotein energy from Intralipid for
      7 d after mid-small bowel resection or transection control surgery. There was no
      evidence of biochemical essential fatty acid (EFA) deficiency in the absence of
      parenteral fat. Resection-induced gut growth occurred independently of parenteral
      LCT based on significant mucosal hyperplasia in the jejunum and ileum. The
      mucosal profile of linoleic acid in the total lipid extract of jejunum increased
      with the presence of parenteral LCT, but decreased with resection without
      differences in arachidonic acid. There were no differences in the jejunal profile
      of 11 (n-6)-derived eicosanoids among the four TPN groups as determined by tandem
      MS. In summary, small bowel resection-induced adaptation occurs independently of
      parenteral LCT, and fat-free TPN without EFA deficiency does not alter the
      profile of jejunal (n-6)-derived eicosanoids. Thus, parenteral administration of
      LCT does not appear to alter jejunal eicosanoid synthesis nor is it beneficial in
      stimulating intestinal adaptation.

PMID- 14704303
TI  - Dietary lignins are precursors of mammalian lignans in rats.
AB  - The mammalian lignans enterolactone (ENL) and enterodiol, commonly found in human
      plasma and urine, are phytoestrogens that may contribute to the prevention of
      breast cancer and coronary heart disease. They are formed by the conversion of
      dietary precursors such as secoisolariciresinol and matairesinol lignans by the
      colonic microflora. The identification of lignins, cell-wall polymers
      structurally related to lignans, as precursors of mammalian lignans is reported
      here for the first time. In study 1, rats were fed rye or wheat bran (15% diet)
      for 5 d. Untreated brans and brans extracted with solvents to remove lignans were
      compared. ENL was estimated in urine samples collected for 24 h by time-resolved
      fluoroimmunoassay. ENL urinary excretion was reduced from 18.6 to 5.3 nmol/d
      (n=8; P<0.001) when lignans were removed from rye bran and from 30.5 to 6.2
      nmol/d (P<0.001) when they were removed from wheat bran. These results suggest
      that lignins, embedded in the cell wall and retained in the bran during solvent
      extraction, account for 26-32% of the ENL formed from cereal brans. In study 2,
      rats were fed a deuterated synthetic lignin (0.2% diet) together with wheat bran
      (15%) for 3 d. The detection of deuterated ENL by LC-tandem MS in urine (20
      nmol/d) clearly confirms the conversion of lignin into mammalian lignans. More
      research is warranted to determine the bioavailability of lignins in the human
      diet.

PMID- 14704304
TI  - Acute ingestion of dietary proteins improves post-exercise liver glutathione in
      rats in a dose-dependent relationship with their cysteine content.
AB  - Dietary sulfur amino acids affect glutathione synthesis, but their acute effect
      under conditions of oxidative stress is unknown. We assessed the effect of the
      selective ingestion of alpha-lactalbumin, a cysteine-rich protein, on glutathione
      homeostasis before a single bout of exhaustive exercise. One hour before a 2-h
      run on a treadmill, untrained rats ingested a meal enriched with either milk
      protein (TMP), alpha-lactalbumin-enriched milk protein (alpha-LAC), glucose
      (GLUC) or milk protein plus 150 mg N-acetyl-L-cysteine, a pharmacologic cysteine
      donor (NAC). Glutathione status was monitored in the blood and measured
      postexercise in the liver and heart. A group of fed sedentary rats was used as a
      control (CON). Blood total glutathione levels declined over time in all test
      groups. Although postexercise heart glutathione did not differ among groups,
      postexercise liver glutathione was curvilinearly related to prior cysteine intake
      (R2=0.999, P<0.05). In alpha-LAC rats, liver glutathione was 60-80% higher than
      in GLUC or CON rats (P<0.05) and did not differ from that of NAC rats. Cysteine
      from dietary proteins exhibits a considerable, dose-dependent and acute
      stimulatory effect on liver glutathione during exercise but does not immediately
      benefit whole-body glutathione homeostasis, presumably because of an overlap
      between the postprandial and exercise-related states.

PMID- 14704305
TI  - Pancreatic lipase-related protein 2 is the major colipase-dependent pancreatic
      lipase in suckling mice.
AB  - Suckling mice express colipase before the expression of pancreatic triglyceride
      lipase. Yet, efficient fat digestion in newborns requires colipase, suggesting
      that colipase may act as a cofactor for another lipase such as pancreatic lipase
      related protein 2 (PLRP2). We determined whether PLRP2 or another lipase depends
      on colipase for maximal activity in newborn mice by analyzing extracts from the
      pancreas of 4-d-old colipase-deficient and PLRP2-deficient mice. Pancreatic
      extracts from colipase-deficient pups had lipase activity that was stimulated
      onefold by the addition of exogenous colipase (P<0.001). The activity was
      completely inhibited by an antibody against pancreatic triglyceride lipase that
      also recognizes PLRP2. In contrast, pancreatic extracts from PLRP2-deficient pups
      had significantly lower baseline activity and no colipase-dependent activity. The
      baseline activity was not inhibited by the anti-pancreatic triglyceride lipase
      antibody or an antibody against carboxyl ester lipase. We next separated the
      extracts into two fractions, one containing PLRP2 and the other devoid of PLRP2.
      All of the colipase-dependent activity segregated with the PLRP2-containing
      fraction, consistent with the conclusion that PLRP2 is the major colipase
      dependent lipase in the pancreas of newborns.

PMID- 14704307
TI  - Soy protein enhances the cholesterol-lowering effect of plant sterol esters in
      cholesterol-fed hamsters.
AB  - This study aimed to investigate whether the combination of plant sterol esters
      (PSE) with soy protein or soy isoflavones may have extra cholesterol-lowering
      effects. Male hamsters (n=20/group) were fed diets containing (g/100 g diet) (A)
      20 casein (control), (B) 0.24 PSE, (C) 20 intact soy protein (replacing casein),
      (D) 0.02 soy isoflavones, (E) 0.24 PSE plus 20 soy protein (replacing casein), or
      (F) 0.24 PSE plus 0.02 soy isoflavones, for 5 wk. All diets contained 0.08 g
      cholesterol/100 g diet. Compared with the control diet, the PSE and soy protein
      diets significantly lowered the plasma total cholesterol concentration by 13%
      (P<0.05) and 9% (P<0.05), respectively, whereas the isoflavone diet (D) had no
      effect. The combination of PSE and soy protein (diet E) decreased plasma total
      cholesterol by 26% (P<0.05). The decrease in plasma cholesterol concentration was
      mainly in the non-HDL fraction. In addition, the combination of PSE and soy
      protein significantly decreased plasma triacylglycerol concentration (37%,
      P<0.05) and reduced cholesterol accumulation in the liver. The abundance of
      hepatic LDL-receptors was not influenced by any of the test diets. PSE
      selectively increased fecal excretion of neutral sterols by 190% (P<0.05),
      whereas soy protein increased fecal excretion of neutral sterols and bile acids
      by 66% (P<0.05) and 130% (P<0.05), respectively. The combination of PSE and soy
      protein increased the fecal excretion of neutral sterols and bile acids compared
      with PSE and soy protein alone. In conclusion, the combination of PSE and soy
      protein more dramatically lowers plasma lipids than the individual ingredients.

PMID- 14704306
TI  - Some dietary fibers increase elimination of orally administered polychlorinated
      biphenyls but not that of retinol in mice.
AB  - Dietary fiber supplementation can increase the size and nutrient absorption
      capacities of the small intestine in some mammals, but does this increase the
      risk of accumulating environmental contaminants? This study addressed this
      question by feeding mice diets containing various types of fiber at 0 or 100 g/kg
      (cellulose, lactosucrose, polydextrose, indigestible dextrin, soy polysaccharide,
      rice bran and chitosan) for 10 wk. During the final 2 wk, the mice were fed
      retinol and a dose of Arochlor 1254 [polychlorinated biphenyls (PCB)] estimated
      to be 5% of the median lethal dose. Accumulation was determined using whole blood
      samples collected on days 1, 3 and 7 as well as eight tissues (whole blood, small
      and large intestine, liver, gall bladder, mesentery, kidney and brain).
      Elimination of Arochlor 1254 and retinol was determined using daily collections
      of feces and urine. The patterns of accumulation and elimination differed between
      Arochlor 1254 and retinol, among tissues, and among mice fed diets with various
      amounts and types of fiber. Dietary fiber supplementation did not decrease
      accumulation of PCB. However, the diet with chitosan increased fecal excretion of
      Arochlor 1254 compared to the fiber-free diet (P<0.05). The diets with
      fermentable fiber (polydextrose, indigestible dextrin and soy polysaccharides)
      increased urinary excretion of PCB compared to the diets with water-insoluble
      fiber (cellulose, rice bran and chitosan; P<0.05). The most efficacious diets for
      minimizing accumulation of environmental contaminants and accelerating
      elimination likely include a combination of soluble and insoluble fiber, but the
      specific types, proportions and amounts remain to be determined.

PMID- 14704308
TI  - Five cysteine-containing compounds have antioxidative activity in Balb/cA mice.
AB  - Balb/cA mice were used to study the in vivo effect of N-acetyl cysteine, S-allyl
      cysteine, S-ethyl cysteine, S-methyl cysteine and S-propyl cysteine, all derived
      from garlic, on glutathione (GSH) concentration and catalase and glutathione
      peroxidase (GPX) activities in plasma, kidney and liver. Cysteine was used for
      comparison. The effects of these compounds on the levels of fibronectin,
      triglyceride (TG), cholesterol and alpha-tocopherol were also evaluated. Cysteine
      or cysteine-containing compounds were added to drinking water at 1 g/L. After 4
      wk of treatment, GSH levels in kidney and liver were greater (P<0.05) than in
      controls. Cysteine decreased catalase and GPX activities in liver, and enhanced
      both Fe2+- and glucose-induced lipid oxidation in plasma, kidney and liver
      compared with the control group (P<0.05). However, the administration of the five
      cysteine-containing compounds enhanced catalase and GPX activities in kidney and
      liver, and reduced Fe2+- and glucose-induced lipid oxidation in plasma, kidney
      and liver compared with the control and cysteine-treated groups (P<0.05). Intake
      of the five cysteine-containing compounds reduced fibronectin, TG and cholesterol
      concentrations in plasma and liver, and increased the alpha-tocopherol
      concentration in plasma, kidney and liver compared with the control and cysteine
      treated groups (P<0.05). The five cysteine-containing compounds derived from
      garlic had marked effects on antioxidant enzymes and spared alpha-tocopherol in
      mice. Furthermore, these compounds reduced fibronectin, TG and cholesterol
      concentrations in plasma. These data indicate that these compounds have a range
      of protective effects for cardiovascular disease prevention or therapy.

PMID- 14704309
TI  - Prebiotic inulin enriched with oligofructose in combination with the probiotics
      Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune
      functions in rats.
AB  - Probiotics (PRO) modulate systemic immunity in animals and humans. In contrast,
      the effects of prebiotics (PRE) on systemic and intestinal immunity have not been
      investigated. Whether the combined application of PRO and PRE [synbiotics (SYN)]
      has synergistic or additive effects is presently unknown. Therefore, PRO
      (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin
      enriched with oligofructose), and SYN (combination of PRO and PRE) were fed to
      F344 rats for 4 wk as supplements to a high fat diet. Functions of immune cells
      isolated from peripheral blood mononuclear cells (PBMC), spleen, mesenterial
      lymph nodes and Peyer's patches (PP) were investigated. The SYN supplement
      increased secretory immunoglobulin A (sIgA) production in the ileum compared with
      controls fed the high fat diet alone (P<0.05), and decreased the oxidative burst
      activity of blood neutrophils (P<0.05) compared with rats fed PRO. The PRE
      supplement enhanced the production of interleukin-10 (P<0.05) in PP as well as
      the production of sIgA in the cecum (P<0.05), compared with controls. The PRO
      supplement modestly affected immune functions, whereas systemic immunomodulatory
      effects were observed in rats fed SYN. The PRE supplement primarily acted at the
      level of the gut-associated lymphoid tissue. The combined application of PRO and
      PRE has different effects from those of the individual supplements, but does not
      simply result in additive or synergistic effects.

PMID- 14704311
TI  - Folic acid deficiency during late gestation decreases progenitor cell
      proliferation and increases apoptosis in fetal mouse brain.
AB  - In mice and rats, maternal dietary choline intake during late pregnancy modulates
      mitosis and apoptosis in progenitor cells of the fetal hippocampus and septum.
      Because choline and folate are interrelated metabolically, we investigated the
      effects of maternal dietary folate availability on progenitor cells in fetal
      mouse telencephalon. Timed-pregnant mice were fed a folate-supplemented (FS),
      control (FCT) or folate-deficient (FD) AIN-76 diet from d 11-17 of pregnancy. FD
      decreased the number of progenitor cells undergoing cell replication in the
      ventricular zones of the developing mouse brain septum (46.6% of FCT), caudate
      putamen (43.5%), and neocortex (54.4%) as assessed using phosphorylated histone
      H3 (a specific marker of mitotic phase) and confirmed by bromodeoxyuridine (BrdU)
      labeling of the S phase. In addition, 106.2% more apoptotic cells were found in
      FD than in FCT fetal septum. We observed 46.8% more calretinin-positive cells in
      the medial septal-diagonal band region of FD compared with pups from control
      dams. FS mice did not differ significantly from FCT mice in any of these
      measures. These results suggest that progenitor cells in fetal forebrain are
      sensitive to maternal dietary folate during late gestation.

PMID- 14704310
TI  - Neurological dysfunction occurs in mice with targeted deletion of the
      selenoprotein P gene.
AB  - Brain function and selenium concentration are well maintained in rodents under
      conditions of selenium deficiency. Recently, however, targeted deletion of the
      selenoprotein P gene (Sepp) has been associated with a decrease in brain selenium
      concentration and with neurological dysfunction. Studies were conducted with
      Sepp(-/-) and Sepp(+/+) mice to characterize the neurological dysfunction and to
      correlate it with dietary selenium level. When weanling Sepp(-/-) mice were fed
      the basal diet (<0.01 mg/kg selenium) supplemented with 0, 0.05 or 0.10 mg
      selenium/kg, they developed spasticity that progressed and required euthanasia.
      Supplementing the diet with > or =0.25 mg selenium/kg prevented the neurological
      dysfunction. To determine whether neurological dysfunction would occur in more
      mature Sepp(-/-) mice deprived of selenium, Sepp(-/-) mice that had been fed the
      basal diet supplemented with 1.0 mg selenium/kg for 4 wk were switched to a
      selenium-deficient diet. Within 3 wk they had developed neurological dysfunction
      and weight loss. At 3 wk, the 1.0 mg selenium/kg diet was reinstituted.
      Neurological function stabilized but did not return to normal. Brain selenium
      concentration did not increase. Weight gain resumed. This study shows that
      neurological dysfunction occurs when selenium supply to the brain is curtailed
      and that the dysfunction is not readily reversible. Both the absence of
      selenoprotein P and a low dietary selenium supply are necessary for the
      dysfunction to occur, indicating that selenoprotein P and at least one other form
      of selenium supply the element to the brain.

PMID- 14704312
TI  - Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat
      brain.
AB  - Studies with animals support a role for vitamin K (VK) in the biosynthesis of
      sphingolipids, a class of complex lipids present in high concentrations in the
      brain. In mice and rats, VK deficiency decreases levels of brain sulfatides and
      causes behavioral alterations. In light of its heterogeneity and to better
      understand the role of VK in the brain, we characterized the distribution of the
      two main VK vitamers, phylloquinone (K1) and menaquinone-4 (MK-4), in nine
      distinct brain regions. Weaning female Sprague-Dawley rats (n=5/dietary group)
      were fed diets containing either low (L, 80 microg/kg diet), adequate (A, 500
      microg/kg diet) or high (H, 2000 microg/kg diet) levels of K1 for 6 mo. The main
      form of VK in the brain was MK-4, and it was present in significantly higher
      concentrations in myelinated regions (the pons medulla and midbrain) than in
      nonmyelinated regions. Both regional K1 and MK-4 increased with K1 intake
      (P<0.05). Sphingolipid distribution varied across brain regions (P<0.001) but was
      not affected by K1 intake. In the L and A groups but not the H group, brain MK-4
      concentration was positively correlated with the concentrations of sulfatides (L,
      r=0.518; A, r=0.479) and sphingomyelin (L, r=0.515; A, r=0.426), and negatively
      correlated with ganglioside concentration (L, r=-0.398); A, r=-0.353).
      Sphingolipids are involved in major cellular events such as cell proliferation,
      differentiation and survival. The strong associations reported here between brain
      MK-4 and sphingomyelin, sulfatides and gangliosides suggest that this vitamer may
      play an important role in the brain.

PMID- 14704313
TI  - Lifetime alcohol consumption and postmenopausal breast cancer rate in Denmark: a
      prospective cohort study.
AB  - Alcohol intake may be one of the few modifiable risk factors for breast cancer.
      In a prospective cohort of 29,875 women with 423 cases of breast cancer during
      1993-2000, we examined the relationship between postmenopausal breast cancer
      incidence rate and alcohol consumption in different life periods. When alcohol
      intake during four age ranges, twenties, thirties, forties and fifties was
      evaluated, only the intake in the fifties increased the risk of breast cancer
      [rate ratio (RR)=1.12 (95% CI: 1.05-1.19)] per 10 g/d increase in alcohol intake.
      After adjustment for intake at study entry, this association was no longer
      present [RR=1.01 (95% CI: 0.91-1.13)]. The cumulative lifetime alcohol intake,
      adjusted for recent intake, showed no association with postmenopausal breast
      cancer risk. Recent alcohol intake, adjusted for the alcohol intake in the other
      life time periods, showed a significant association of RR=1.09 (95% CI: 1.00
      1.18) per 10 g/d. There was no indication of a higher risk among women with early
      drinking start, nor did women who started to drink before their first birth have
      a higher risk than women who started to drink later in life. Our results suggest
      that baseline intake of alcohol is a more important determinant of postmenopausal
      breast cancer risk than earlier lifetime exposure.

PMID- 14704314
TI  - Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild
      type mice from carcinogen-induced colon cancer.
AB  - Consumption of soy foods has been weakly associated with reduced colon cancer
      risk. Colon cancer risk is influenced by estrogen exposure, although the
      mechanism through which this occurs is not defined. Conversion of estradiol (E2)
      to estrone (E1) may be protective in the colon. We hypothesized that dietary
      phytoestrogens, or E1, would reduce colon tumorigenesis via an estrogen receptor
      (ER)-dependent mechanism. Ovariectomized ERalphaKO or wild-type (WT) female mice
      were fed diets containing casein (Casein), soy protein without isoflavones (Soy
      IF), soy protein + genistein (Soy+Gen), soy protein + NovaSoy (Soy+NSoy) or soy
      protein + estrone (Soy+E1) from weaning. Colon tumors were induced with
      azoxymethane. Tumor incidence was affected by diet but not genotype. Colon tumor
      incidence was lower in ERalphaKO and WT mice fed the Soy+E1 diet compared with
      those fed the casein or Soy-IF diets. Mice fed Soy+NSoy had a lower tumor
      incidence than mice fed casein, but not Soy-IF. Genistein did not affect tumor
      incidence. Soy protein, independently of phytoestrogens or E1, significantly
      reduced relative colon weight, tumor burden and multiplicity. Relative colon
      weight was lower (P=0.008) in mice fed Soy+E1 than in the other soy-fed groups.
      Tumor incidence in this group was lower than in the casein and soy-IF-fed groups
      and tended to be lower than in the others (P=0.020). Hence, soy protein and NSoy
      protect mice from colon cancer, and E1 further reduces colon tumorigenesis in
      mice, independently of ERalpha.

PMID- 14704315
TI  - Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our
      ancient diet, epidemiology and randomized controlled trials.

PMID- 14704316
TI  - Are the current dietary guidelines regarding egg consumption appropriate?

PMID- 14704317
TI  - A critical evaluation of the fetal origins hypothesis and its implications for
      developing countries.

PMID- 14704318
TI  - Modeling fetal adaptation to nutrient restriction: testing the fetal origins
      hypothesis with a supply-demand model.
AB  - The fetal origins hypothesis (FOH) posits that fetal adaptations to nutritional
      insufficiency elevate future risk for cardiovascular disease (CVD). Although
      birth weight (BW) remains the most commonly used index of fetal nutritional
      sufficiency in FOH research, it is a poor index of fetal nutrition because it is
      also influenced by genes, epigenetic effects and other nonnutritional factors.
      This paper uses data from the Cebu Longitudinal Health and Nutrition Survey
      (CLHNS) to explore an alternate strategy--the supply-demand model--as a means to
      model fetal nutritional sufficiency, adaptation and cardiovascular programming.
      Specifically, it is hypothesized that small size should be associated with
      elevated CVD risk, but only when there is corroborating evidence that the
      individual had a higher growth potential, was born to a nutritionally stressed
      mother, or both. Using low density lipoprotein cholesterol (LDL-C) and systolic
      blood pressure (SBP) as markers of CVD risk, the predictions of the model are
      only met for LDL-C and only in males. There is evidence for an association
      between maternal nutritional status and male offspring SBP, but this relationship
      is independent of fetal nutritional sufficiency as defined by the model. Thus,
      although both the LDL-C and SBP findings support the general hypothesis that the
      prenatal milieu has long-term implications for CVD risk in males, only the
      patterns observed for LDL-C are consistent with the prediction that fetal
      nutritional sufficiency is key to CVD programming.

PMID- 14704319
TI  - Modeling postnatal exposures and their interactions with birth size.
AB  - The fetal origins of adult disease hypothesis postulates that the inverse
      association between birth weight and later adverse outcome reflects fetal
      programming that increases the risk of later disease. However, low birth weight
      is associated with catch-up after birth, and weight gain is itself a risk factor
      for later disease. It is difficult to disentangle the effects on outcome of the
      size and growth components of weight change through time. This paper presents the
      life course plot, a device to display both size and growth effects
      simultaneously. It is based on the multiple-regression analysis of the outcome on
      the various weights, expressed as z-scores, and the plot displays the
      coefficients plotted against the corresponding ages of measurement. Examples from
      Brazil (Pelotas) and the Phillippines (Cebu) relate blood pressure in adolescence
      to weight through childhood. They show small inverse weight effects in infancy,
      but early weight is less important than weight and weight gain during
      adolescence. In addition, birth length in the Cebu study affects the strength of
      the relationship between weight and blood pressure in adolescence. This suggests
      a fetal programming effect, with children who were relatively long at birth
      having a more sensitive relationship between blood pressure and weight at age 15.
      Whether this is a good or a bad thing is not immediately clear.

PMID- 14704320
TI  - Early life origins of insulin resistance and type 2 diabetes in India and other
      Asian countries.
AB  - There is a rapidly increasing epidemic of type 2 diabetes in India and other
      Asian countries. The thrifty genotype and the thrifty phenotype are two
      nonexclusive explanations. People in the Indian subcontinent have faced
      undernutrition for many generations, and Indian babies are among the smallest in
      the world. However, the diabetes epidemic is of recent origin, and diabetes is
      more common among urban than rural Indians despite the higher birth weight of
      urban babies. This suggests that postnatal factors must also contribute. Thus, a
      life-course model of evolution of insulin resistance and type 2 diabetes,
      incorporating fetal, postnatal and adult components, seems most appropriate. For
      a given BMI, Indians have a higher percentage of body fat and more visceral fat
      than members of other populations. This thin-fat phenotype is present at birth.
      Neonatal size and body composition are influenced by parental size, maternal food
      intake, physical activity and circulating concentrations of nutrients and
      metabolites (folate, glucose, triglycerides, cholesterol etc.). Maternal insulin
      resistance promotes transfer of nutrients to the fetus. Accelerated childhood
      growth is another risk factor for adiposity and insulin resistance, especially in
      children born small. Childhood growth seems to be more influenced by paternal
      genetic factors, whereas intrauterine growth is more influenced by maternal
      factors (intrauterine environment). Urban lifestyles, including poor diet and
      sedentary habits, promote further obesity, insulin resistance and type 2
      diabetes. These factors may be amenable to correction. Prevention of type 2
      diabetes must begin in utero and continue throughout the life course.

PMID- 14704321
TI  - Historic and early life origins of hypertension in Africans.
AB  - Cardiovascular disease (CVD) causes 12.4 million deaths annually, most (9.6
      million) occurring in developing countries. Hypertension, the most common CVD,
      arises within the context of obesity, but the underlying mechanisms remain
      obscure. Obesity and salt intake are two important risk factors for hypertension
      and are the focus of this paper. Traditional African populations show a low
      prevalence of hypertension, but hypertension is more common in migrant African
      populations in the West than in other ethnic groups. One explanation is genetic,
      but no causative gene has been confidently identified. Nongenetic
      susceptibilities such as fetal programming are an alternative explanation.
      Hypothetically, fetal programming induced by transient stimuli permanently alters
      fetal structure and function at the cellular, organ and whole-body levels. Birth
      weight is inversely related to blood pressure and hypertension risk, suggesting
      that susceptibility to hypertension risk factors such as obesity and salt
      sensitivity are themselves programmed. In support of this hypothesis, obesity
      (especially central obesity) is also inversely related to size at birth.
      Likewise, salt sensitivity might derive from undernutrition in utero, reducing
      the nephron number and resetting the pressure-natriuresis curve rightward.
      However, no robust human data or evidence of enhanced salt sensitivity among
      African-origin populations exist. In the United States, blacks have a greater
      prevalence of low birth weight than whites, suggesting that the higher prevalence
      of hypertension among blacks is related to fetal programming. Nevertheless, we
      need to be scrupulous in ascribing risk to the myriad other confounders of this
      relationship, including environmental and behavioral correlates of ethnicity,
      before concluding that excess risk of hypertension in Africans is programmed in
      utero.

PMID- 14704322
TI  - Functions and actions of retinoids and carotenoids: building on the vision on
      James Allen Olson. Proceedings of a symposium to honor the memory of James Allen
      Olson. June 21-24, 2001, Ames, Iowa, USA.

PMID- 14704323
TI  - Carotenoids in health and disease: recent scientific evaluations, research
      recommendations and the consumer.
AB  - In addition to his many research achievements, James Allen Olson made important
      contributions to evaluations of the role of dietary carotenoids in prevention of
      chronic diseases such as cancer, heart disease and age-related macular
      degeneration in well-nourished populations. This paper reviews recent scientific
      evaluations of the role of carotenoids in disease, recommendations for future
      research, and consumer-related trends of relevance to carotenoids. Authoritative
      scientific evaluations by key leading thinkers have not been able to ascribe a
      disease prevention function to carotenoids because of the absence of definitive
      evidence. These leading thinkers recommend that future research on the role of
      carotenoids in disease focus on the complexities of diet, genetics and
      environment in the disease process. This research is important to make it
      possible for consumers to derive optimal health promoting benefits from fruits
      and vegetables in the context of changing dietary patterns.

PMID- 14704324
TI  - From 1989 to 2001: what have we learned about the "biological actions of beta
      carotene"?
AB  - Dr. James Allen Olson helped us to define the role of beta-carotene in human
      health by categorizing these as "functions, actions and associations." In the
      last decade, significant research has shown that beta-carotene acts as an
      antioxidant in biologically relevant systems, affects several aspects of human
      immune function and higher intake/serum levels are associated with improvements
      in certain physiological functions such as lung function. The unexpected findings
      of increased lung cancer in beta-carotene supplemented smokers in the ATBC and
      CARET intervention studies have resulted in the need for expanded research
      efforts to define the mechanism(s) of action of beta-carotene. Recent survey data
      as well as laboratory animal studies continue to find an inverse association
      between beta-carotene and cancer risk. Because beta-carotene is the major source
      of vitamin A for the majority of the world's population, it is critical to define
      the safe levels of intake from foods and supplements.

PMID- 14704325
TI  - Vitamin A deficiency disorders: international efforts to control a preventable
      "pox".
AB  - Visual symptoms (night blindness) of vitamin A deficiency (VAD) were among the
      earliest diet-related deficiencies documented. Knowledge of vitamin A chemistry,
      metabolism and deficiency consequences accrued rapidly during the first eight
      decades of the 20th century. A series of disorders were described in animals,
      including impaired growth, reproduction, epithelial integrity, and disease
      resistance that were relieved by consumption of both animal and plant sources of
      the vitamin. Identification of the intestinal beta-carotene cleavage enzyme in
      the laboratory of James Allen Olson was seminal to understanding the mechanism
      for formation of vitamin A from ingested carotenoids. WHO's 1990 estimate of
      about 40 million children annually with clinical eye signs of VAD was revised
      upward to 140-250 million at risk of vitamin A deficiency disorders (VADD) when
      epidemiological and clinical trials demonstrated morbidity and mortality risk
      even in the absence of ocular signs. Alternative methods for VAD status
      assessment and more reliable analytical techniques were developed, several in Dr.
      Olson's laboratory. The last decade has seen global progress in VADD control by
      expanding distribution of medicinal supplements, fortification of foods and
      dietary diversification through horticulture and education programs. Experience
      shows that achievements gained through narrowly focused interventions are fragile
      and vulnerable to national political and economic instability. Contextually
      relevant, community-centered strategies that improve household food and nutrition
      security and self-reliance are critical to sustaining international efforts to
      control the VADD "pox."

PMID- 14704327
TI  - Alpha and omega of carotenoid cleavage.
AB  - In early 1900s, based on indirect evidence, Steenbock and Morton independently
      predicted that beta-carotene could be the biological precursor of vitamin A,
      although this notion was contested by others. In the 1930s, Thomas Moore showed
      the in vivo formation of vitamin A from beta-carotene. But it was not until Jim
      Olson and DeWitt Goodman independently showed in 1965 the formation of retinal,
      the aldehyde form of vitamin A from beta-carotene in cell-free extracts of liver
      and intestine, that this vital pathway of beta-carotene was recognized. Despite
      compelling evidence in several experimental systems for the central cleavage of
      beta-carotene to retinal by many investigators, there were some careful
      independent studies by Glover et al., Ganguly et al., Hansen and Meret and
      Krinsky et al. showing the eccentric cleavage of beta-carotene resulting in the
      formation of apocarotenoids both in vivo and in vitro. In an attempt to resolve
      this controversial issue, we revisited this problem in 1989 and showed beyond
      doubt the formation of retinal as the sole enzymatic product of a cytosolic
      enzyme from rabbit and rat intestinal mucosa by mass spectrometry and tracer
      analysis of the crystallized product. This was confirmed in 1996 by Nagao using
      the pig intestinal extract. Yeum et al. confirmed in 2000 that retinal is the
      sole product of beta-carotene cleavage in the presence of alpha-tocopherol, and
      that the observed formation of apocarotenoids occurs only in the absence of an
      antioxidant like alpha-tocopherol. In the same year, Barua and Olson also
      concluded from their in vivo studies in rats that central cleavage is by far the
      major pathway for the formation of vitamin A from beta-carotene. Beta, beta
      carotene 15,15'-dioxygenase (EC 1.13.11.21) is the key enzyme that cleaves beta
      carotene into two molecules of retinal. It is a cytosolic enzyme primarily
      localized in the duodenal mucosa although it has been found in liver. It is a 66
      kDa sulfhydryl protein, requires molecular oxygen and is activated by ferrous
      ions. It is highly specific for 15:15' ethylenic bond of carotenoids although it
      has fairly broad specificity towards a number of carotenoids with at least one
      intact beta-ionone ring. The dioxygenase was recently cloned from Drosophila
      melanogaster and from the chicken intestine. The recombinant protein was found to
      form retinal as the sole cleavage product of beta-carotene. No apo-carotenoids
      were formed. Therefore, it is unequivocally proven that the major, if not the
      sole, pathway of beta-carotene cleavage to vitamin A is by oxidative cleavage of
      the central ethylenic bond of beta-carotene to yield two molecules of retinal.
      Most recently, human dioxygenase has also been cloned. Thus, the wisdom, vision
      and epoch-making mission of Jim Olson in the science of beta-carotene metabolism
      have been accomplished. I have no doubt that the impact of his original discovery
      of the dioxygenase and its importance in vitamin A nutriture should be
      forthcoming in the near future.

PMID- 14704326
TI  - Oxidative conversion of carotenoids to retinoids and other products.
AB  - In vertebrates, provitamin A carotenoids are converted to retinal by beta
      carotene-15,15'-dioxygenase. The enzyme activity is expressed specifically in
      intestinal epithelium and in liver. The intestinal enzyme not only plays an
      important role in providing animals with vitamin A, but also determines whether
      provitamin A carotenoids are converted to vitamin A or circulated in the body as
      intact carotenoids. We have found that a high fat diet enhanced the beta-carotene
      dioxygenase activity together with the cellular retinol binding protein type II
      level in rat intestines. Flavonols with a catechol structure in the B-ring and
      2,6-di-tert-butyl-4-methylphenol inhibited the dioxygenase activity of pig
      intestinal homogenates and the conversion of beta-carotene to retinol in Caco-2
      human intestinal cells. Thus, the bioavailability of dietary provitamin A
      carotenoids might be modulated by the other food components ingested. Regulation
      of the dioxygenase activity and its relation to the retinoid metabolism as well
      as to lipid metabolism deserve further study. In contrast to enzymatic cleavage,
      it is known that both retinal and beta-apocarotenals are formed in vitro from
      beta-carotene by chemical transformation, which cleaves conjugated double bonds
      at random positions under various oxidative conditions. Moreover, recent studies
      have indicated that the oxidation products formed by chemical transformation
      might have specific actions on the proliferation of certain cancer cells. We have
      found that lycopene, a typical nonprovitamin A carotenoid, was cleaved in vitro
      to acycloretinal, acycloretinoic acid and apolycopenals in a nonenzymatic manner,
      and that the mixture of oxidation products of lycopene induced apoptosis of HL-60
      human promyelocytic leukemia cells. Thus, it is worth evaluating the formation of
      oxidation products and their biological actions, in order to elucidate the
      underlying mechanisms of the beneficial effects of carotenoids on human health.

PMID- 14704328
TI  - Carotene oxygenases: a new family of double bond cleavage enzymes.
AB  - Beta,beta-carotene 15,15'-monooxygensae (betaCMOOX) is the key enzyme involved in
      the metabolism of provitamin A carotenoids to retinal. Although the enzyme has
      been known for >40 y, it has been only within the last 2 y that the cloning and
      the molecular characterization of the betaCMOOX from several species was reported
      in literature. New clones of the carotene metabolizing enzyme have emerged, all
      belonging to the family of double bond cleavage enzymes, suggesting common
      ancestry. BetaCMOOX cleaves beta,beta-carotene to retinal in an in vitro activity
      assay; no apo-carotenals were identified. The second enzyme involved in
      carotenoid metabolism, beta,beta-carotene 9',10'-dioxygenase, is responsible for
      the excentric cleavage pathway of carotenoids, cleaving beta,beta-carotene to 10'
      apo-carotenal and beta-ionone. In an expression overview, the betaCMOOX was
      detected in duodenum, liver, kidney and in the lungs of chickens. In mice, the
      mRNA for the central cleavage enzyme was highly expressed in liver, testes, small
      intestine, and kidney. betaCMOOX expression was highest in epithelial and
      endothelial structures in both species. These results suggest that the source of
      vitamin A originates from carotenoids in the corresponding tissues, in addition
      to retinol supplied from liver stores.

PMID- 14704329
TI  - Vitamin A formation in animals: molecular identification and functional
      characterization of carotene cleaving enzymes.
AB  - Vitamin A and its derivatives (retinoids) are essential components in vision;
      they contribute to pattern formation during development and exert multiple
      effects on cell differentiation. It has been known for 70 y that the key step in
      vitamin A biosynthesis is the oxidative cleavage of a carotenoid with provitamin
      A activity. While a detailed biochemical characterization of the respective
      enzymes could be achieved in cell-free homogenates, their molecular nature has
      remained elusive for a long time. Recent research led to the identification of
      genes encoding two different types of carotene oxygenases from animal species.
      The molecular cloning of these different types of animal carotene oxygenases
      establishes the existence of a family of carotenoid metabolizing enzymes in
      animals heretofore described in plants. With these tools in hands, old questions
      in vitamin A research can be definitively addressed on the molecular levels
      contributing to a mechanistic understanding of the regulation of vitamin A
      homeostasis or tissue specificity of vitamin A formation, with impact on animal
      physiology and human health.

PMID- 14704330
TI  - Carotenoid action on the immune response.
AB  - Early studies demonstrating the ability of dietary carotenes to prevent
      infections have left open the possibility that the action of these carotenoids
      may be through their prior conversion to vitamin A. Subsequent studies to
      demonstrate the specific action of dietary carotenoids have used carotenoids
      without provitamin A activity such as lutein, canthaxanthin, lycopene and
      astaxanthin. In fact, these nonprovitamin A carotenoids were as active, and at
      times more active, than beta-carotene in enhancing cell-mediated and humoral
      immune response in animals and humans. Another approach to study the possible
      specific role of dietary carotenoids has used animals that are inefficient
      converters of carotenoids to vitamin A, for example the domestic cat. Results
      have similarly shown immuno-enhancement by nonprovitamin A carotenoids, based
      either on the relative activity or on the type of immune response affected
      compared to beta-carotene. Certain carotenoids, acting as antioxidants, can
      potentially reduce the toxic effects of reactive oxygen species (ROS). These ROS,
      and therefore carotenoids, have been implicated in the etiology of diseases such
      as cancer, cardiovascular and neurodegenerative diseases and aging. Recent
      studies on the role of carotenoids in gene regulation, apoptosis and angiogenesis
      have advanced our knowledge on the possible mechanism by which carotenoids
      regulate immune function and cancer.

PMID- 14704331
TI  - The enigma of beta-carotene in carcinogenesis: what can be learned from animal
      studies.
AB  - Beta-carotene and other carotenoids have been thought to have anti-cancer
      activity, either because of antioxidant activity or because of their ability to
      be converted to vitamin A. Nevertheless, two large scale intervention studies in
      humans using high doses of beta-carotene found that beta-carotene supplementation
      resulted in more lung cancer rather than less lung cancer among smoking and
      asbestos exposed populations. Studies conducted in the ferret have elucidated
      molecular mechanisms behind this observation, in that high-dose beta-carotene and
      smoke exposure in these animals leads to squamous metaplasia, a pre-cancerous
      lesion in the lung. High dose beta-carotene in the smoke exposed animals was
      found to give rise to a number of transient oxidative metabolites, which include
      P450 enzymes that result in the destruction of retinoic acid, and diminished
      retinoid signaling, and enhanced cell proliferation. In addition, eccentric
      cleavage beta-carotene metabolites facilitate the binding of smoke derived
      carcinogens to DNA. In other ferret studies low dose beta-carotene smoke exposure
      provided mild protection against squamous metaplasia. Thus, it appears that the
      explanation of the apparent paradoxical effects of beta-carotene on lung cancer
      is related to dose. The metabolism and breakdown of natural products should be
      thoroughly investigated in animal models before embarking on large scale
      intervention trials, particularly when using unusually high doses that greatly
      exceed normal dietary levels.

PMID- 14704332
TI  - Regulation of hepatic retinol metabolism: perspectives from studies on vitamin A
      status.
AB  - Liver vitamin A (retinol) is obtained from several sources and is subject to
      multiple fates. Lecithin:retinol acyltransferase (LRAT), a microsomal enzyme
      present in liver and several other retinol-metabolizing tissues, esterifies
      retinol that is associated with a cellular retinol-binding protein, CRBP or CRBP
      II. Recent research has shown that LRAT mRNA expression and enzyme activity are
      regulated in a tissue-specific manner. In vitamin A-deficient liver, both LRAT
      mRNA and activity are significantly down-regulated as well as rapidly induced
      after the administration of vitamin A or its principal hormonal metabolite,
      retinoic acid (RA). In long-term feeding studies and the metabolic steady state,
      liver LRAT is expressed dose-dependently across a wide range of dietary vitamin
      A. Additionally, an RA-inducible cytochrome P450, P450RAI or CYP26, is down
      regulated in liver during vitamin A deficiency and up-regulated dose-dependently
      by dietary vitamin A and exogenous RA. Based on these results, we propose that
      LRAT and CYP26 serve as two molecular mechanisms, coordinately regulated by all
      trans-RA, to control the availability of retinol and RA, respectively. The LRAT
      reaction, besides providing a readily retrievable storage form of vitamin A, may
      regulate the availability of retinol to other pathways, while the CYP26 reaction
      may serve to prevent a detrimental "overshoot" of RA concentration. Moreover,
      retinoid metabolism in the liver is likely to be closely integrated with that in
      peripheral tissues through the rapid interorgan transfer and recycling of
      retinoids, affecting the whole-body economy of vitamin A.

PMID- 14704333
TI  - Vitamin A: overlapping delivery pathways to tissues from the circulation.
AB  - Although retinol bound to retinol-binding protein (RBP) is the most abundant
      retinoid form present in the circulations of humans and most mammals, other
      retinoid and proretinoid forms are also present in the blood. We are interested
      in understanding to what extent each of these circulating retinoid forms
      contributes towards retinoid actions within cells and tissues. Here we report two
      studies focused on this question. First, we examined retinoid transport and
      storage in RBP-deficient mice that lack circulating RBP. These mice under normal
      laboratory conditions are phenotypically normal except for a visual impairment
      early in life that is corrected if the mice are maintained on a vitamin A
      sufficient diet throughout life. The RBP-deficient mice take up vitamin A from
      the diet into most tissues at least as well as wild type mice. Compared to wild
      type mice, mice lacking RBP accumulate excess vitamin A in the liver, since there
      is no RBP to facilitate mobilization of stored retinol from hepatic stores. In a
      second study, we explored in vitro the actions of carotene cleavage enzyme (CCE)
      in facilitating beta-carotene cleavage to retinoid in the testis. CCE is most
      highly expressed in the testis. Pull-down experiments coupled with MALDI-MS
      analysis showed that mouse testis CCE is able to interact with the testis
      specific lactate dehydrogenase-C (LDH-C) isoform. This may suggest that CCE and
      LDH-C act in concert to catalyze beta-carotene cleavage.

PMID- 14704334
TI  - Analysis of retinoids and carotenoids: problems resolved and unsolved.
AB  - Progress in nutritional biochemistry has always depended on progress in analysis
      of nutrients. Animal growth assays were fundamentally important in the discovery
      and initial isolation of the fat-soluble vitamins. Chromatography, initially
      introduced by Tswett for separation of plant pigments (including carotenoids),
      quickly became indispensable for separation of carotenoids and vitamin A
      compounds; the early open-column methods were eventually superseded by more
      efficient HPLC techniques, and reversed-phase HPLC has become the current method
      of choice for analysis of retinoids and carotenoids in biological tissues.
      Detection and quantitation of retinoids and carotenoids most often has depended
      on their unparalleled spectral properties; the conjugated polyene structures of
      these compounds give them unique light absorption spectra and high molar
      absorptivities, and hence outstanding lower limits of detection. Other
      techniques, such as gas chromatography (GC) and mass spectroscopy (coupled with
      GC and HPLC), immunoassays, supercritical fluid chromatography, and capillary
      electrophoresis, have proven useful in certain applications. Analysis of retinoid
      binding proteins has been mostly by conventional protein methods, although the
      fluorescence of the retinol ligand has been useful in some instances to provide a
      highly specific assay. Current challenges in retinoid and carotenoid analysis
      include the resolution of stereoisomers, and quantitation of these compounds at
      ultratrace levels in biological tissues. Possible new approaches include
      accelerator mass spectroscopy, and use of gene expression assays to assess
      vitamin A status.

PMID- 14704335
TI  - Retinoyl beta-glucuronide: a biologically active interesting retinoid.
AB  - Numerous reports have indicated that the biological activity of all-trans
      retinoyl beta-glucuronide (RAG) is similar to that of all-trans-retinoic acid
      (RA), but without the toxic side effects of RA. In the present series of studies,
      we report new findings that support the contention that RAG can function as a
      nontoxic substitute for RA in a variety of clinic settings. One study on the
      effects of s.c. injected graded doses of RA and RAG (20-480 micromol/kg BW) into
      pregnant Sprague-Dawley rats showed that any differences between RAG and RA could
      be observed only at the highest dose levels of 360 and 420 micromol/kg BW, with
      RAG being much less toxic than RA. Similarly, daily topical application of RAG
      (0.16-1.6%) and RA (0.1-0.5%) to shaved swine dorsal skin for six mo resulted in
      redness and scabbing in RA-treated patches, and to a lesser extent in 1.6% RAG
      treated, but not in other RAG-treated patches. Histological scores were
      significantly higher in the dermis and epidermis of RA-treated pigs than in RAG
      treated pigs. Studies to document the pharmacokinetics of chronically
      administered RAG in mice indicated that, unlike RA, sustained blood levels of
      parent retinoid (RAG) can be achieved during at least 2 mo of daily
      administration. Another investigation to study the effects of RAG on the
      development and growth in nude mice of tumors derived from the human
      neuroblastoma cell line LA-N-5 showed that s.c. injection of RAG (30 micromol/kg
      BW) reduced tumor formation when the retinoid was first administered 3 d before
      tumor injection and continued daily for 30 d thereafter. In established tumors,
      RAG was shown to inhibit progressive tumor growth, the antitumor effects of RAG
      being comparable with RA. However, with RAG, as opposed to RA, there were no
      significant adverse physical side effects. Based on the results of these series
      of studies along with ample published reports over the last 15 y, we conclude
      that RAG may be a safe and effective alternative to RA and some other retinoids
      that are presently being utilized in the clinic.

PMID- 14704336
TI  - Assessing vitamin A status: past, present and future.
AB  - Xerophthalmia classification was traditionally used to identify populations with
      vitamin A deficiency. Currently, night blindness and dark adaptometry have been
      proposed as population assessment methods. While eye signs and function tests are
      still used in areas where vitamin A deficiency is severe, a subclinical vitamin A
      deficiency is more prevalent. Serum and breast milk retinol concentrations are
      used to identify vitamin A deficiency risk. However, in healthy individuals,
      serum retinol concentrations are homeostatically controlled and do not begin to
      decline until liver reserves of vitamin A are dangerously low. Moreover, serum
      retinol and retinol binding protein (RBP) concentrations fall during times of
      infection. The RBP:transthyretin ratio may help to determine if serum retinol
      concentrations are depressed by infection. Other methods better reflect liver
      reserves of vitamin A, the "gold" standard. The relative dose response and
      modified relative dose response tests involve giving a small dose of retinyl or
      dehydroretinyl ester, respectively, and determining a response in the serum at
      about 5 h. A new response test where retinoyl beta-glucuronide is administered
      and the degree of hydrolysis to retinoic acid is measured has been investigated.
      Unlike isotope dilution tests, the dose response tests lack utility in defining
      the total body reserve of vitamin A. The deuterated retinol isotope dilution test
      has been used in several different groups. Recently, a new isotope assay was
      developed using 13C-retinyl acetate and gas chromatography-combustion-isotope
      ratio mass spectrometry for analysis. Thus, having many choices of vitamin A
      assessment methods, laboratory sophistication and resources available will
      usually dictate which methods are chosen.

PMID- 14704338
TI  - ARAGORN, a program to detect tRNA genes and tmRNA genes in nucleotide sequences.
AB  - A computer program, ARAGORN, identifies tRNA and tmRNA genes. The program employs
      heuristic algorithms to predict tRNA secondary structure, based on homology with
      recognized tRNA consensus sequences and ability to form a base-paired cloverleaf.
      tmRNA genes are identified using a modified version of the BRUCE program. ARAGORN
      achieves a detection sensitivity of 99% from a set of 1290 eubacterial,
      eukaryotic and archaeal tRNA genes and detects all complete tmRNA sequences in
      the tmRNA database, improving on the performance of the BRUCE program. Recently
      discovered tmRNA genes in the chloroplasts of two species from the 'green' algae
      lineage are detected. The output of the program reports the proposed tRNA
      secondary structure and, for tmRNA genes, the secondary structure of the tRNA
      domain, the tmRNA gene sequence, the tag peptide and a list of organisms with
      matching tmRNA peptide tags.

PMID- 14704337
TI  - DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA
      helicase A and hnRNP proteins in an RNA-dependent manner.
AB  - An RNA-dependent association of Ku antigen with nuclear DNA helicase II (NDH II),
      alternatively named RNA helicase A (RHA), was found in nuclear extracts of HeLa
      cells by immunoprecipitation and by gel filtration chromatography. Both Ku
      antigen and NDH II were associated with hnRNP complexes. Two-dimensional gel
      electrophoresis showed that Ku antigen was most abundantly associated with hnRNP
      C, K, J, H and F, but apparently not with others, such as hnRNP A1. Unexpectedly,
      DNA-dependent protein kinase (DNA-PK), which comprises Ku antigen as the DNA
      binding subunit, phosphorylated hnRNP proteins in an RNA-dependent manner. DNA-PK
      also phosphorylated recombinant NDH II in the presence of RNA. RNA binding assays
      displayed a preference of DNA-PK for poly(rG), but not for poly(rA), poly(rC) or
      poly(rU). This RNA binding affinity of DNA-PK can be ascribed to its Ku86
      subunit. Consistently, poly(rG) most strongly stimulated the DNA-PK-catalyzed
      phosphorylation of NDH II. RNA interference studies revealed that a suppressed
      expression of NDH II altered the nuclear distribution of hnRNP C, while silencing
      DNA-PK changed the subnuclear distribution of NDH II and hnRNP C. These results
      support the view that DNA-PK can also function as an RNA-dependent protein kinase
      to regulate some aspects of RNA metabolism, such as RNA processing and transport.

PMID- 14704339
TI  - GenoFrag: software to design primers optimized for whole genome scanning by long
      range PCR amplification.
AB  - Genome sequence data can be used to analyze genome plasticity by whole genome PCR
      scanning. Small sized chromosomes can indeed be fully amplified by long-range PCR
      with a set of primers designed using a reference strain and applied to several
      other strains. Analysis of the resulting patterns can reveal the genome
      plasticity. To facilitate such analysis, we have developed GenoFrag, a software
      package for the design of primers optimized for whole genome scanning by long
      range PCR. GenoFrag was developed for the analysis of Staphylococcus aureus
      genome plasticity by whole genome amplification in approximately 10 kb-long
      fragments. A set of primers was generated from the genome sequence of S.aureus
      N315, employed here as a reference strain. Two subsets of primers were
      successfully used to amplify two portions of the N315 chromosome. This
      experimental validation demonstrates that GenoFrag is a robust and reliable tool
      for primer design and that whole genome PCR scanning can be envisaged for the
      analysis of genome diversity in S.aureus, one of the major public health concerns
      worldwide.

PMID- 14704340
TI  - RB signaling prevents replication-dependent DNA double-strand breaks following
      genotoxic insult.
AB  - Cell cycle checkpoints induced by DNA damage play an integral role in
      preservation of genomic stability by allowing cells to limit the propagation of
      deleterious mutations. The retinoblastoma tumor suppressor (RB) is crucial for
      the maintenance of the DNA damage checkpoint function because it elicits cell
      cycle arrest in response to a variety of genotoxic stresses. Although sporadic
      loss of RB is characteristic of most cancers and results in the bypass of the DNA
      damage checkpoint, the consequence of RB loss upon chemotherapeutic
      responsiveness has been largely uninvestigated. Here, we employed a conditional
      knockout approach to ablate RB in adult fibroblasts. This system enabled us to
      examine the DNA damage response of adult cells following acute RB deletion. Using
      this system, we demonstrated that loss of RB disrupted the DNA damage checkpoint
      elicited by either cisplatin or camptothecin exposure. Strikingly, this bypass
      was not associated with enhanced repair, but rather the accumulation of
      phosphorylated H2AX (gammaH2AX) foci, which indicate DNA double-strand breaks.
      The formation of gammaH2AX foci was due to ongoing replication following
      chemotherapeutic treatment in the RB-deficient cells. Additionally, peak
      gammaH2AX accumulation occurred in S-phase cells undergoing DNA replication in
      the presence of damage, and these gammaH2AX foci co-localized with replication
      foci. These results demonstrate that acute RB loss abrogates DNA damage-induced
      cell cycle arrest to induce gammaH2AX foci formation. Thus, secondary genetic
      lesions induced by RB loss have implications for the chemotherapeutic response
      and the development of genetic instability.

PMID- 14704342
TI  - Interactions between the 2.4 and 4.2 regions of sigmaS, the stress-specific sigma
      factor of Escherichia coli, and the -10 and -35 promoter elements.
AB  - The sigmas subunit of Escherichia coli RNA polymerase holoenzyme (EsigmaS) is a
      key factor of gene expression upon entry into stationary phase and in stressful
      conditions. The selectivity of promoter recognition by EsigmaS and the
      housekeeping Esigma70 is as yet not clearly understood. We used a genetic
      approach to investigate the interaction of sigmaS with its target promoters.
      Starting with down-promoter variants of a sigmaS promoter target, osmEp, altered
      in the -10 or -35 elements, we isolated mutant forms of sigmaS suppressing the
      promoter defects. The activity of these suppressors on variants of osmEp and
      ficp, another target of sigmaS, indicated that sigmaS is able to interact with
      the same key features within a promoter sequence as sigma70. Indeed, (i) sigmaS
      can recognize the -35 element of some but not all its target promoters, through
      interactions with its 4.2 region; and (ii) amino acids within the 2.4 region
      participate in the recognition of the -10 element. More specifically, residues
      Q152 and E155 contribute to the strong preference of sigmaS for a C in position 
      13 and residue R299 can interact with the -31 nucleotide in the -35 element of
      the target promoters.

PMID- 14704341
TI  - The last CTD repeat of the mammalian RNA polymerase II large subunit is important
      for its stability.
AB  - The phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD) has
      been shown to affect the initiation, and transition to elongation of the Pol II
      complex. The differential phosphorylation of serines within this domain coincides
      with the recruitment of factors important for pre-mRNA processing and
      transcriptional elongation. A role for tyrosine and threonine phosphorylation has
      yet to be described. The discovery of kinases that express a preference for
      specific residues within this sequence suggests a mechanism for the controlled
      recruitment and displacement of CTD-interacting partners during the transcription
      cycle. The last CTD repeat (CTD52) contains unique interaction sites for the only
      known CTD tyrosine kinases, Abl1/c-Abl and Abl2/Arg, and the serine/threonine
      kinase casein kinase II (CKII). Here, we show that removal or severe disruption
      of the last CTD repeat, but not point mutation of its CKII sites, results in its
      proteolytic degradation to the Pol IIb form in vivo, but does not appear to
      affect the specific transcription of genes. These results suggest a possible
      mechanism of transcription control through the proteolytic removal of the Pol II
      CTD.

PMID- 14704343
TI  - Role of intrinsic DNA binding specificity in defining target genes of the
      mammalian transcription factor PDX1.
AB  - PDX1 is a homeodomain transcription factor essential for pancreatic development
      and mature beta cell function. Homeodomain proteins typically recognize short
      TAAT DNA motifs in vitro: this binding displays paradoxically low specificity and
      affinity, given the extremely high specificity of action of these proteins in
      vivo. To better understand how PDX1 selects target genes in vivo, we have
      examined the interaction of PDX1 with natural and artificial binding sites.
      Comparison of PDX1 binding sites in several target promoters revealed an
      evolutionarily conserved pattern of nucleotides flanking the TAAT core. Using
      competitive in vitro DNA binding assays, we defined three groups of binding sites
      displaying high, intermediate and low affinity. Transfection experiments revealed
      a striking correlation between the ability of each sequence to activate
      transcription in cultured beta cells, and its ability to bind PDX1 in vitro. Site
      selection from a pool of oligonucleotides (sequence NNNTAATNNN) revealed a non
      random preference for particular nucleotides at the flanking locations,
      resembling natural PDX1 binding sites. Taken together, the data indicate that the
      intrinsic DNA binding specificity of PDX1, in particular the bases adjacent to
      TAAT, plays an important role in determining the spectrum of target genes.

PMID- 14704344
TI  - Echinomycin inhibits chromosomal DNA replication and embryonic development in
      vertebrates.
AB  - Echinomycin, a member of the quinoxaline family of antibiotics, is known to be a
      strong inhibitor of RNA synthesis which has been attributed to its ability to
      bind to double-helical DNA. Here we study the effect of echinomycin upon DNA
      replication using egg extracts and embryos from Xenopus laevis as well as
      cultured human cells. Evidence is presented that echinomycin interferes with
      chromatin decondensation, nuclear assembly and DNA replication. In the absence of
      transcription and translation, the drug specifically blocks DNA replication in
      both Xenopus sperm chromatin and HeLa cell nuclei in vitro. By contrast,
      replication of single-stranded DNA is not inhibited indicating that echinomycin
      acts by interacting with the DNA and not the replication elongation proteins of
      chromatin. The addition of the antibiotic to HeLa cells and X.laevis embryos
      results in anaphase bridges and cell death. Importantly, in X.laevis embryos
      injected with echinomycin at the two-cell stage the drug specifically inhibits
      the cell cycle prior to the onset of transcription, suggesting that quinoxaline
      antibiotics could exert anti- proliferative effects by inhibition of chromosomal
      DNA replication.

PMID- 14704345
TI  - The major human AP endonuclease (Ape1) is involved in the nucleotide incision
      repair pathway.
AB  - In nucleotide incision repair (NIR), an endonuclease nicks oxidatively damaged
      DNA in a DNA glycosylase-independent manner, providing the correct ends for DNA
      synthesis coupled to the repair of the remaining 5'-dangling modified nucleotide.
      This mechanistic feature is distinct from DNA glycosylase-mediated base excision
      repair. Here we report that Ape1, the major apurinic/apyrimidinic endonuclease in
      human cells, is the damage- specific endonuclease involved in NIR. We show that
      Ape1 incises DNA containing 5,6-dihydro-2'-deoxyuridine, 5,6-dihydrothymidine, 5
      hydroxy-2'-deoxyuridine, alpha-2'-deoxyadenosine and alpha-thymidine adducts,
      generating 3'-hydroxyl and 5'-phosphate termini. The kinetic constants indicate
      that Ape1-catalysed NIR activity is highly efficient. The substrate specificity
      and protein conformation of Ape1 is modulated by MgCl2 concentrations, thus
      providing conditions under which NIR becomes a major activity in cell-free
      extracts. While the N-terminal region of Ape1 is not required for AP endonuclease
      function, we show that it regulates the NIR activity. The physiological relevance
      of the mammalian NIR pathway is discussed.

PMID- 14704346
TI  - Structural and biochemical analyses of hemimethylated DNA binding by the SeqA
      protein.
AB  - The Escherichia coli SeqA protein recognizes the 11 hemimethylated G-mA-T-C sites
      in the oriC region of the chromosome, and prevents replication over-initiation
      within one cell cycle. The crystal structure of the SeqA C-terminal domain with
      hemimethylated DNA revealed the N6-methyladenine recognition mechanism; however,
      the mechanism of discrimination between the hemimethylated and fully methylated
      states has remained elusive. In the present study, we performed mutational
      analyses of hemimethylated G-mA-T-C sequences with the minimal DNA-binding domain
      of SeqA (SeqA71-181), and found that SeqA71-181 specifically binds to
      hemimethylated DNA containing a sequence with a mismatched mA:G base pair [G
      mA(:G)-T-C] as efficiently as the normal hemimethylated G-mA(:T)-T-C sequence. We
      determined the crystal structures of SeqA71-181 complexed with the mismatched and
      normal hemimethylated DNAs at 2.5 and 3.0 A resolutions, respectively, and found
      that the mismatched mA:G base pair and the normal mA:T base pair are recognized
      by SeqA in a similar manner. Furthermore, in both crystal structures, an electron
      density is present near the unmethylated adenine, which is only methylated in the
      fully methylated state. This electron density, which may be due to a water
      molecule or a metal ion, can exist in the hemimethylated state, but not in the
      fully methylated state, because of steric clash with the additional methyl group.

PMID- 14704347
TI  - Yeast telomerase is capable of limited repeat addition processivity.
AB  - Telomerase is a ribonucleoprotein reverse transcriptase responsible for the
      maintenance of one strand of telomere terminal repeats. Telomerase-mediated
      sequence addition is dictated by a short 'template' region of the RNA component.
      Despite the short template segment, telomerases from many organisms have been
      shown to mediate the synthesis of long extension products. This synthesis
      presumably depends on two types of translocation events: simultaneous
      translocation of the RNA-DNA duplex relative to the active site after each
      nucleotide incorporation (type I or nucleotide addition processivity), and
      translocation of the RNA relative to the DNA product after each round of repeat
      synthesis (type II or repeat addition processivity). In contrast, telomerases
      from yeasts have been shown to synthesize mostly short products, implying a
      defect in one or both types of translocation. In this report, we analyzed the
      processivity of yeast telomerase in vitro, and identified two position-specific
      elongation barriers within the 5' region of the RNA template that can account for
      the synthesis of incomplete first round products. These barriers respond
      differently to variations in nucleotide concentration, primer sequence and
      mutations in the catalytic protein subunit, consistent with their having distinct
      mechanistic bases. In addition, by using optimal primers and high concentrations
      of dGTP, we were able to detect significant type II translocation by the yeast
      enzyme. Thus, the difference between the elongation property of yeast and other
      telomerases appears to be quantitative rather than qualitative. Our results
      suggest that yeast may be a useful system for investigating the physiologic
      significance of repeat addition processivity.

PMID- 14704348
TI  - The major role of human AP-endonuclease homolog Apn2 in repair of abasic sites in
      Schizosaccharomyces pombe.
AB  - The abasic (AP) sites, the major mutagenic and cytotoxic genomic lesions, induced
      directly by oxidative stress and indirectly after excision of damaged bases by
      DNA glycosylases, are repaired by AP-endonucleases (APEs). Among two APEs in
      Saccharomyces cerevisiae, Apn1 provides the major APE activity, and Apn2, the
      ortholog of the mammalian APE, provides back-up activity. We have cloned apn1 and
      apn2 genes of Schizosaccharomyces pombe, and have shown that inactivation of Apn2
      and not Apn1 sensitizes this fission yeast to alkylation and oxidative damage
      inducing agents, which is further enhanced by Apn1 inactivation. We also show
      that Uve1, present in S.pombe but not in S.cerevisiae, provides the back-up APE
      activity together with Apn1. We confirmed the presence of APE activity in
      recombinant Apn2 and in crude cell extracts. Thus S.pombe is distinct from
      S.cerevisiae, and is similar to mammalian cells in having Apn2 as the major APE.

PMID- 14704349
TI  - Formation of DNA nanoparticles in the presence of novel polyamine analogues: a
      laser light scattering and atomic force microscopic study.
AB  - We synthesized a pentamine (3-3-3-3) and two hexamine (3-3-3-3-3 and 3-4-3-4-3)
      analogues of the natural polyamine, spermine (3-4-3) and studied their
      effectiveness in condensing pGL3 plasmid DNA, using light scattering and atomic
      force microscopic (AFM) techniques. The midpoint concentration of the polyamines
      on pGL3 condensation (EC50) was 11.3, 10.6, 1.5, 0.49 and 0.52 micro M,
      respectively, for 3-4-3, norspermine (3-3-3), 3-3-3-3, 3-3-3-3-3 and 3-4-3-4-3 in
      10 mM Na cacodylate buffer. Dynamic laser light scattering study showed a
      decrease in hydrodynamic radii of plasmid DNA particles as the number of positive
      charges on the polyamines increased. AFM data showed the presence of toroids with
      outer diameter of 117-191 nm for different polyamines, and a mean height of 2.61
      +/- 0.77 nm. AFM results also revealed the presence of intermediate structures,
      including those showing circumferential winding of DNA to toroids. The dependence
      of the EC50 on Na+ concentration suggests different modes of binding of spermine
      and its higher valent analogues with DNA. Our results show a 20-fold increase in
      the efficacy of hexamines for DNA condensation compared to spermine, and provide
      new insights into the mechanism(s) of DNA nanoparticle formation. These studies
      might help to develop novel nonviral gene delivery vehicles.

PMID- 14704350
TI  - Automatic extraction of mutations from Medline and cross-validation with OMIM.
AB  - Mutations help us to understand the molecular origins of diseases. Researchers,
      therefore, both publish and seek disease-relevant mutations in public databases
      and in scientific literature, e.g. Medline. The retrieval tends to be time
      consuming and incomplete. Automated screening of the literature is more
      efficient. We developed extraction methods (called MEMA) that scan Medline
      abstracts for mutations. MEMA identified 24,351 singleton mutations in
      conjunction with a HUGO gene name out of 16,728 abstracts. From a sample of 100
      abstracts we estimated the recall for the identification of mutation-gene pairs
      to 35% at a precision of 93%. Recall for the mutation detection alone was >67%
      with a precision rate of >96%. This shows that our system produces reliable data.
      The subset consisting of protein sequence mutations (PSMs) from MEMA was compared
      to the entries in OMIM (20,503 entries versus 6699, respectively). We found 1826
      PSM-gene pairs to be in common to both datasets (cross-validated). This is 27% of
      all PSM-gene pairs in OMIM and 91% of those pairs from OMIM which co-occur in at
      least one Medline abstract. We conclude that Medline covers a large portion of
      the mutations known to OMIM. Another large portion could be artificially produced
      mutations from mutagenesis experiments. Access to the database of extracted
      mutation-gene pairs is available through the web pages of the EBI (refer to
      http://www.ebi. ac.uk/rebholz/index.html).

PMID- 14704351
TI  - Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes.
AB  - Recent studies have begun to reveal that numerous fundamental metabolic pathways
      in bacteria are regulated by riboswitches residing within certain messenger RNAs.
      These riboswitches selectively bind metabolites and modulate gene expression in
      response to changing ligand concentrations. Previously, we provided evidence that
      the btuB mRNAs of Escherichia coli and Salmonella typhimurium each carry a
      coenzyme B12-dependent riboswitch that causes repressed translation of the
      encoded cobalamin-transport protein at elevated coenzyme concentrations. Herein,
      we use a phylogenetic analysis to define a consensus sequence and secondary
      structure model for the ligand- binding domain of this riboswitch class. RNA
      structures that conform to this model are widespread in both Gram-positive and
      Gram-negative organisms. In addition, we find that the 5'-untranslated region (5'
      UTR) of the cobalamin biosynthesis (cob) operon of S.typhimurium carries an RNA
      motif that matches this consensus sequence. Biochemical and genetic
      characterization of this motif confirms that the RNA directly binds coenzyme B12,
      and that it likely serves as a genetic control element for regulating expression
      of the 25-gene operon for cobalamin production in this pathogen.

PMID- 14704352
TI  - Polyamine derivatives as selective RNaseA mimics.
AB  - Site-selective scission of ribonucleic acids (RNAs) has attracted considerable
      interest, since RNA is an intermediate in gene expression and the genetic
      material of many pathogenic viruses. Polyamine-imidazole conjugates for site
      selective RNA scission, without free imidazole, were synthesized and tested on
      yeast phenylalanine transfer RNA. These molecules catalyze RNA hydrolysis non
      randomly. Within the polyamine chain, the location of the imidazole residue, the
      numbers of nitrogen atoms and their relative distances have notable influence on
      cleavage selectivity. A norspermine derivative reduces the cleavage sites to a
      unique location, in the anticodon loop of the tRNA, in the absence of
      complementary sequence. Experimental results are consistent with a cooperative
      participation of an ammonium group of the polyamine moiety, in addition to it's
      binding to the negatively charged ribose-phosphate backbone, as proton source,
      and the imidazole moiety as a base. There is correlation between the location of
      the magnesium binding sites and the RNA cleavage sites, suggesting that the
      protonated nitrogens of the polycationic chain compete with some of the magnesium
      ions for RNA binding. Therefore, the cleavage pattern is specific of the RNA
      structure. These compounds cleave at physiological pH, representing novel
      reactive groups for antisense oligonucleotide derivatives or to enhance ribozyme
      activity.

PMID- 14704353
TI  - A 21-amino acid peptide from the cysteine cluster II of the family D DNA
      polymerase from Pyrococcus horikoshii stimulates its nuclease activity which is
      Mre11-like and prefers manganese ion as the cofactor.
AB  - Family D DNA polymerase (PolD) is a new type of DNA polymerase possessing
      polymerization and 3'-5' exonuclease activities. Here we report the
      characterization of the nuclease activity of PolD from Pyrococcus horikoshii. By
      site-directed mutagenesis, we verified that the putative Mre11-like nuclease
      domain in the small subunit (DP1), predicted according to computer analysis and
      structure inference reported previously, is the catalytic domain. We show that
      D363, H365 and H454 are the essential residues, while D407, N453, H500, H563 and
      H565 are critical residues for the activity. We provide experimental evidence
      demonstrating that manganese, rather than magnesium, is the preferable metal ion
      for the nuclease activity of PolD. We also show that DP1 alone is insufficient to
      perform full catalysis, which additionally requires the formation of the PolD
      complex and manganese ion. We found that a 21 amino acid, subunit-interacting
      peptide of the sequence from cysteine cluster II of the large subunit (DP2)
      stimulates the exonuclease activity of DP1 and the internal deletion mutants of
      PolD lacking the 21-aa sequence. This indicates that the putative zinc finger
      motif of the cysteine cluster II is deeply involved in the nucleolytic catalysis.

PMID- 14704354
TI  - Domain mapping of the Rad51 paralog protein complexes.
AB  - The five human Rad51 paralogs are suggested to play an important role in the
      maintenance of genome stability through their function in DNA double-strand break
      repair. These proteins have been found to form two distinct complexes in vivo,
      Rad51B-Rad51C-Rad51D-Xrcc2 (BCDX2) and Rad51C-Xrcc3 (CX3). Based on the recent
      Pyrococcus furiosus Rad51 structure, we have used homology modeling to design
      deletion mutants of the Rad51 paralogs. The models of the human Rad51B, Rad51C,
      Xrcc3 and murine Rad51D (mRad51D) proteins reveal distinct N-terminal and C
      terminal domains connected by a linker region. Using yeast two-hybrid and co
      immunoprecipitation techniques, we have demonstrated that a fragment of Rad51B
      containing amino acid residues 1-75 interacts with the C-terminus and linker of
      Rad51C, residues 79-376, and this region of Rad51C also interacts with mRad51D
      and Xrcc3. We have also determined that the N-terminal domain of mRad51D,
      residues 4-77, binds to Xrcc2 while the C-terminal domain of mRad51D, residues 77
      328, binds Rad51C. By this, we have identified the binding domains of the BCDX2
      and CX3 complexes to further characterize the interaction of these proteins and
      propose a scheme for the three-dimensional architecture of the BCDX2 and CX3
      paralog complexes.

PMID- 14704355
TI  - Computational inference of transcriptional regulatory networks from expression
      profiling and transcription factor binding site identification.
AB  - We have developed a computational method for transcriptional regulatory network
      inference, CARRIE (Computational Ascertainment of Regu latory Relationships
      Inferred from Expression), which combines microarray and promoter sequence
      analysis. CARRIE uses sources of data to identify the transcription factors (TFs)
      that regulate gene expression changes in response to a stimulus and generates
      testable hypotheses about the regulatory network connecting these TFs to the
      genes they regulate. The promoter analysis component of CARRIE, ROVER (Relative
      OVER-abundance of cis-elements), is highly accurate at detecting the TFs that
      regulate the response to a stimulus. ROVER also predicts which genes are
      regulated by each of these TFs. CARRIE uses these transcriptional interactions to
      infer a regulatory network. To demonstrate our method, we applied CARRIE to six
      sets of publicly available DNA microarray experiments on Saccharomyces
      cerevisiae. The predicted networks were validated with comparisons to literature
      sources, experimental TF binding data, and gene ontology biological process
      information.

PMID- 14704356
TI  - Finding functional sequence elements by multiple local alignment.
AB  - Algorithms that detect and align locally similar regions of biological sequences
      have the potential to discover a wide variety of functional motifs. Two
      theoretical contributions to this classic but unsolved problem are presented
      here: a method to determine the width of the aligned motif automatically; and a
      technique for calculating the statistical significance of alignments, i.e. an
      assessment of whether the alignments are stronger than those that would be
      expected to occur by chance among random, unrelated sequences. Upon exploring
      variants of the standard Gibbs sampling technique to optimize the alignment, we
      discovered that simulated annealing approaches perform more efficiently. Finally,
      we conduct failure tests by applying the algorithm to increasingly difficult test
      cases, and analyze the manner of and reasons for eventual failure. Detection of
      transcription factor-binding motifs is limited by the motifs' intrinsic subtlety
      rather than by inadequacy of the alignment optimization procedure.

PMID- 14704357
TI  - Domainal organization of the lower eukaryotic homologs of the yeast RNA
      polymerase II core subunit Rpb7 reflects functional conservation.
AB  - The subcomplex of Rpb4 and Rpb7 subunits of RNA pol II in Saccharomyces
      cerevisiae is known to be an important determinant of transcription under a
      variety of physiological stresses. In S.cerevisiae, RPB7 is essential for cell
      viability while rpb4 null strains are temperature sensitive at low and high
      temperatures. The rpb4 null strain also shows defect in sporulation and a
      predisposed state of pseudohyphal growth. We show here that, apart from
      S.cerevisiae Rpb7, the Rpb7 homologs from other lower eukaryotes like
      Schizosaccharomyces pombe, Candida albicans and Dictyostelium discoideum can
      complement for the absence of S.cerevisiae RPB7. This is the first report where
      we have shown that both the C.albicans and D.discoideum homologs are functional
      orthologs of the yeast RPB7. We also show that high expression levels of
      S.cerevisiae RPB7 and its homologs rescue the sporulation defect of rpb4
      homozygous null diploids, but only some of them cause significant enhancement of
      the pseudohyphal phenotype. Structural modeling of Rpb7 and its homologs show a
      high degree of conservation in the overall structure. This study indicates a
      structural and functional conservation of different Rpb7 across species and also
      a conserved role of Rpb7 in the subcomplex with respect to nutritional stress.

PMID- 14704358
TI  - Dual-regulated expression of C/EBP-alpha and BMP-2 enables differential
      differentiation of C2C12 cells into adipocytes and osteoblasts.
AB  - CCAAT/enhancer-binding proteins (C/EBPs) as well as bone morphogenic proteins
      (BMPs) play essential roles in mammalian cell differentiation in shaping
      adipogenic and osteoblastic lineages in particular. Recent evidence suggested
      that adipocytes and osteoblasts share a common mesenchymal precursor cell
      phenotype. Yet, the molecular details underlying the decision of adipocyte versus
      osteoblast differentiation as well as the involvement of C/EBPs and BMPs remains
      elusive. We have engineered C2C12 cells for dual-regulated expression of human
      C/EBP-alpha and BMP-2 to enable independent transcription control of both
      differentiation factors using clinically licensed antibiotics of the
      streptogramin (pristinamycin) and tetracycline (tetracycline) classes.
      Differential as well as coordinated expression of C/EBP-alpha and BMP-2 revealed
      that (i) C/EBP-alpha may differentiate C2C12 myoblasts into adipocytes as well as
      osteoblasts, (ii) BMP-2 prevents myotube differentiation, (iii) is incompetent in
      differentiating C2C12 into osteoblasts and (iv) even decreases C/EBP-alpha's
      osteoblast-specific differentiation potential but (v) cooperates with C/EBP-alpha
      on adipocyte differentiation, (vi) osteoblast formation occurs at low C/EBP-alpha
      levels while adipocyte-specific differentiation requires maximum C/EBP-alpha
      expression and that (vii) BMP-2 may bias the C/EBP-alpha-mediated adipocyte
      versus osteoblast differentiation switch towards fat cell formation. Dual
      regulated expression technology enabled precise insight into combinatorial
      effects of two key differentiation factors involved in adipocyte/osteoblast
      lineage control which could be implemented in rational reprogramming of
      multipotent cells into desired cell phenotypes tailored for gene therapy and
      tissue engineering.

PMID- 14704359
TI  - Ligase-mediated construction of branched DNA strands: a novel DNA joining
      activity catalyzed by T4 DNA ligase.
AB  - Branched nucleic acid strands exist as intermediates in certain biological
      reactions, and bifurcating DNA also presents interesting opportunities in
      biotechnological applications. We describe here how T4 DNA ligase can be used for
      efficient construction of DNA molecules having one 5' end but two distinct 3'
      ends that extend from the 2' and 3' carbons, respectively, of an internal
      nucleotide. The nature of the reaction products is investigated, and optimal
      reaction conditions are reported for the construction of branched
      oligonucleotides. We discuss the utility of these branched DNA nanostructures for
      gene detection.

PMID- 14704360
TI  - Facile methods for generating human somatic cell gene knockouts using recombinant
      adeno-associated viruses.
AB  - Emerging evidence suggests that recombinant adeno-associated viral (rAAV) vectors
      can be used for specific gene targeting in human somatic cells. We have developed
      an rAAV vector construction procedure employing fusion PCR and a single cloning
      step that considerably simplifies the knockout process. We demonstrate its
      utility by disrupting genes at specific positions within human colon cancer cells
      as well as within immortalized normal epithelial cells. This technology should be
      broadly applicable to in vitro studies that require the manipulation of the human
      genome.

PMID- 14704361
TI  - Specific cleavage of DNA molecules at RecA-mediated triple-strand structure.
AB  - A novel procedure to cleave DNA molecules at any desired base sequence is
      presented. This procedure is based upon our finding that double-stranded DNA
      molecules at a site where RecA-mediated triple-stranded DNA structure with a
      complimentary deoxyoligonucleotide is located can be cleaved by a single-strand
      specific nuclease, such as nuclease S1 or BAL31, between the first base at the 5'
      termini of the deoxyoligonucleotides and the nearest base proximal to the 5'
      termini. Accordingly, the sequence as well as the number of the cleavage sites to
      be cleaved can be custom designed by selecting deoxyoligonucleotides with
      specific base sequences for triple-stranded DNA formation. The basic
      characteristics of the cleavage reaction and typical applications of the
      procedure are presented with actual results, including those which involve
      cleavage of complex genomic DNA at the very sites one desires.

PMID- 14704362
TI  - SNP2CAPS: a SNP and INDEL analysis tool for CAPS marker development.
AB  - With the influx of various SNP genotyping assays in recent years, there has been
      a need for an assay that is robust, yet cost effective, and could be performed
      using standard gel-based procedures. In this context, CAPS markers have been
      shown to meet these criteria. However, converting SNPs to CAPS markers can be a
      difficult process if done manually. In order to address this problem, we describe
      a computer program, SNP2CAPS, that facilitates the computational conversion of
      SNP markers into CAPS markers. 413 multiple aligned sequences derived from barley
      ESTs were analysed for the presence of polymorphisms in 235 distinct restriction
      sites. 282 (90%) of 314 alignments that contain sequence variation due to SNPs
      and InDels revealed at least one polymorphic restriction site. After reducing the
      number of restriction enzymes from 235 to 10, 31% of the polymorphic sites could
      still be detected. In order to demonstrate the usefulness of this tool for marker
      development, we experimentally validated some of the results predicted by
      SNP2CAPS.

PMID- 14704363
TI  - Improved full-length cDNA production based on RNA tagging by T4 DNA ligase.
AB  - Second-strand cDNA priming is a central problem for full-length characterization
      of transcripts. A new strategy using bacteriophage T4 DNA ligase and partially
      degenerate adapters is proposed for grafting a sequence tag to the end of
      polyribonucleotides. Based on this RNA tagging system and previously described
      protocols, a new method for full-length cDNA production has been implemented.
      Validation of the method is shown in Arabidopsis thaliana by the construction of
      a full-length cDNA library and the analysis of 154 clones and by 5'-RACE-PCR run
      on a documented experimental system.

PMID- 14704364
TI  - Down-regulation of Hox A7 is required for cell adhesion and migration on
      fibronectin during early HL-60 monocytic differentiation.
AB  - Hox genes, which are key regulators of cell fate and pattern formation during
      embryogenesis, are also important regulators of hematopoiesis, and different
      combinations of Hox gene products are involved in lineage commitment or
      maturation. However, their molecular and cellular modes of action are not yet
      completely understood. Recent studies have indicated that Hox genes are involved
      in the regulation of cell-extracellular matrix (ECM) interactions and cell
      migration. Here, we report that Hox A7, a gene frequently overexpressed in acute
      myeloid leukemia, is down-regulated during HL-60 monocytic differentiation. Using
      a model in which HL-60 cells are induced to differentiate toward the monocytic
      lineage with bone marrow stromal-like cells, we demonstrate that Hox A7-sustained
      expression disturbs the regulation of cell adhesive and migratory capacities on
      fibronectin during early differentiation. We show that this is accompanied by a
      partial blockage of the transcriptional induction of proline-rich tyrosine kinase
      2, a gene coding for a focal adhesion kinase active in monocytes, and of tissue
      transglutaminase, a gene coding for a fibronectin coreceptor in monocytes. This
      is the first report that demonstrates the involvement of a Hox gene in the
      regulation of adhesion and migration of hematopoietic cells and that links it to
      the deregulation of genes involved in cell-ECM interactions and downstream
      signaling pathways.

PMID- 14704365
TI  - GRK6 deficiency is associated with enhanced CXCR4-mediated neutrophil chemotaxis
      in vitro and impaired responsiveness to G-CSF in vivo.
AB  - The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4)
      signaling pathway is thought to play an important role in the induction of
      neutrophil mobilization from the bone marrow in response to granulocyte-colony
      stimulating factor (G-CSF) treatment. CXCR4 belongs to the family of G protein
      coupled receptors. Multiple members of this receptor family are desensitized by
      agonist-induced G protein-coupled receptor kinase (GRK)-mediated phosphorylation.
      Here, we demonstrate that in vitro SDF-1-induced chemotaxis of bone marrow
      derived neutrophils from GRK6-deficient mice is significantly enhanced and that
      desensitization of the calcium response to SDF-1 is impaired in GRK6-/-
      neutrophils. CXCR4 activation by SDF-1 provides a key retention signal for
      hematopoietic cells in the bone marrow. It is interesting that we observed that
      in the absence of GRK6, the G-CSF-induced increase in circulating neutrophils is
      profoundly impaired. Three days after injection of pegylated-G-CSF, significantly
      lower numbers of circulating neutrophils were observed in GRK6-/- as compared
      with wild-type (WT) mice. In addition, early/acute neutrophil mobilization in
      response to G-CSF (3 h after treatment) was also impaired in GRK6-/- mice.
      However, blood neutrophil levels in untreated GRK6-/- and WT mice were not
      different. Moreover, the percentage of neutrophils in the bone marrow after G-CSF
      treatment was increased to the same extent in WT and GRK6-/- mice, indicating
      that neutrophil production is normal in the absence of GRK6. However, the
      increased chemotactic sensitivity of GRK6-/- neutrophils to SDF-1 was retained
      after G-CSF treatment. In view of these data, we suggest that the impaired G-CSF
      induced neutrophil mobilization in the absence of GRK6 may be a result of
      enhanced CXCR4-mediated retention of PMN in the bone marrow.

PMID- 14704366
TI  - Neutrophil chemoattractant genes KC and MIP-2 are expressed in different cell
      populations at sites of surgical injury.
AB  - KC and macrophage-inflammatory protein-2 (MIP-2) are CXC chemokines that exhibit
      distinct temporal patterns of expression in the skin following surgical injury.
      In situ hybridization analysis demonstrates that these two chemokines are
      expressed by distinct cell types at different times following injury. Dermal
      fibroblasts and endothelial cells are primarily responsible for KC expression in
      the skin 6 h following surgery. In contrast, MIP-2 production appears to be
      restricted to infiltrating inflammatory leukocytes including neutrophils and
      monocytes, which appear later in the response. This cell type-specific pattern of
      chemokine expression is recapitulated in vitro using isolated primary- and long
      term-cultured cell types. Primary dermal fibroblasts stimulated with interleukin
      1alpha express predominantly KC and very little MIP-2, and peritoneal exudate
      neutrophils produce as much or more MIP-2 as KC following stimulation in vitro.
      Although a collection of exogenous stimuli can induce expression of KC and MIP-2,
      the quantitative ratio for expression reflects the cell type and not the
      stimulus. The selective expression of KC over MIP-2 in endothelial cells results
      from markedly greater KC gene transcription and not from alterations in the rate
      of mRNA decay. These results demonstrate that distinct CXC chemokines show
      restricted expression in myeloid versus nonmyeloid cell types and that patterns
      of chemokine expression at sites of inflammation in vivo reflect the temporally
      ordered contribution of these distinct cell types.

PMID- 14704367
TI  - Expression and synthesis of fibroblast growth factor-9 in human gammadelta T
      lymphocytes. Response to isopentenyl pyrophosphate and TGF-beta1/IL-15.
AB  - Gammadelta T-lymphocytes are believed to play a role in maintaining the normal
      configuration of epithelial tissue. As little is known about the factors
      mediating this function, we addressed the question of whether gammadelta T
      lymphocytes produce fibroblast growth factor (FGF)-9 as well as two other growth
      factors associated with epithelial tissue reconstitution. Blood gammadelta T
      cells isolated from healthy donors were grown in the presence of isopentenyl
      pyrophosphate (IPP) or transforming growth factor-beta1 (TGF-beta1)/interleukin
      15 (IL-15) for 24 h and were assessed for the expression and synthesis of FGF-9,
      keratinocyte growth factor (KGF), and epidermal growth factor (EGF). Resting
      human gammadelta T cells constitutively expressed KGF and FGF-9 mRNA but no EGF
      mRNA. In the presence of IPP, FGF-9 mRNA expression significantly increased in a
      dose-dependent manner, expression of KGF remained unaltered, and EGF mRNA could
      not be detected. In contrast to IPP, stimulation of the cells with TGF-beta1/IL
      15 did not alter FGF-9 expression. Moreover, stimulation with anti-CD3 does not
      induce FGF-9 expression but triggers a high signal of interferon-gamma mRNA.
      Western blot analysis of gammadelta T cell lysates, prepared 4 days following
      stimulation with IPP, showed an increase of FGF-9 protein as compared with
      control cells. In conclusion, the results demonstrate for the first time that
      human blood and bronchoalveolar lavage gammadelta T-lymphocytes are capable of
      expressing FGF-9. The data also provide novel evidence that immunoregulatory
      cells can synthesize FGF-9.

PMID- 14704369
TI  - Limitations with in vitro production of dendritic cells using cytokines.
AB  - Dendritic cells (DC) are the most effective antigen-presenting cells. Many
      studies now show that DC can be generated in vitro from a number of starting cell
      populations containing hematopoietic precursors. The protocols used involve
      different combinations of cytokines including granulocyte macrophage-colony
      stimulating factor (GM-CSF), which supports myeloid precursors, or interleukin-7,
      which supports lymphoid precursors. DC are commonly generated by in vitro culture
      of bone marrow or monocytes with GM-CSF and other cytokines. However, these
      cultures do not sustain DC production for long periods of time and do not allow
      the identification or study of intermediate stages in cell development. In vitro
      cytokine-dependent cultures of DC precursors do provide a reliable source of DC
      for stimulating immune responses. However, use of cells produced in cytokine
      dependent cultures for the study of DC differentiation is limited, as DC
      development in vivo differs in cytokine dependency.

PMID- 14704368
TI  - The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during
      recognition of apoptotic thymocytes by murine macrophages.
AB  - Apoptotic leukocytes must be cleared efficiently by macrophages (Mo). Apoptotic
      cell phagocytosis by Mo requires the receptor tyrosine kinase (RTK) MerTK (also
      known as c-Mer and Tyro12), the phosphatidylserine receptor (PS-R), and the
      classical protein kinase C (PKC) isoform betaII, which translocates to Mo
      membrane and cytoskeletal fractions in a PS-R-dependent manner. How these
      molecules cooperate to induce phagocytosis is unknown. As the
      phosphatidylinositol-specific phospholipase (PI-PLC) gamma2 is downstream of RTKs
      in some cell types and can activate classical PKCs, we hypothesized that MerTK
      signals via PLC gamma2. To test this hypothesis, we examined the interaction of
      MerTK and PLC gamma2 in resident, murine peritoneal (P)Mo and in the murine Mo
      cell line J774A.1 (J774) following exposure to apoptotic thymocytes. We found
      that as with PMo, J774 phagocytosis of apoptotic thymocytes was inhibited by
      antibody against MerTK. Western blotting and immunoprecipitation showed that
      exposure to apoptotic cells produced three time-dependent changes in PMo and
      J774: tyrosine phosphorylation of MerTK; association of PLC gamma2 with MerTK;
      and tyrosine phosphorylation of PLC gamma2. Cross-linking MerTK using antibody
      also induced phosphorylation of PLC gamma2 and its association with MerTK. A PI
      PLC appears to be required for phagocytosis of apoptotic cells, as the PI-PLC
      inhibitor Et-18-OCH3 and the PLC inhibitor U73122, but not the inactive control
      U73343, blocked phagocytosis without impairing adhesion. On apoptotic cell
      adhesion to Mo, MerTK signals at least in part via PLC gamma2.

PMID- 14704370
TI  - Combined activation of innate and T cell immunity for recognizing
      immunomodulatory properties of therapeutic agents.
AB  - Complex syndromes such as atherosclerosis and type 2 diabetes are disorders that
      are associated with inflammatory processes involving innate and adaptive
      immunity. Emerging knowledge about the pathological consequences of immune
      imbalances in a wide range of disease settings is expected to help to identify
      novel therapeutic targets. However, current test systems for immunomodulatory
      drugs tend to be too simplistic, as they rely only on cells of the innate- or the
      adaptive-immune system, or they are complex, in vivo models, which are not
      suitable for screening purposes. Using a modified mixed lymphocyte culture (MMLC)
      assay for combined analysis of innate and adaptive immunity, we show that this
      assay is very sensitive for the presence of low concentrations of
      immunomodulatory agents. Low-dose lipopolysaccharide stimulation of cells from
      two unrelated donors yields a strong cytokine response including interleukin (IL)
      12 and IL-18, which induce interferon-gamma as a potential analysis parameter. As
      the MMLC assay is based on the mutual interaction of cells of the innate and
      adaptive immunity, it enables the monitoring of cytokine release under almost
      physiological conditions and might be of interest for the characterization of
      known and novel drugs concerning their immunomodulatory potency.

PMID- 14704371
TI  - Why Old McDonald had a farm but no allergies: genes, environments, and the
      hygiene hypothesis.

PMID- 14704373
TI  - Metabolic studies with radioactive carbon, 11C: A. Baird Hastings.

PMID- 14704372
TI  - Effects of cholera toxin on innate and adaptive immunity and its application as
      an immunomodulatory agent.
AB  - Cholera toxin (CT) is a potent vaccine adjuvant when administered via parenteral,
      mucosal, or transcutaneous routes. It also inhibits innate inflammatory responses
      induced by pathogen-derived molecules, such as lipopolysaccharide (LPS). We
      demonstrated previously that CT promotes the induction of regulatory type 1 T
      cells (Tr1) as well as T helper type 2 cells (Th2). T cells from mice immunized
      with antigen in the presence of CT produced high levels of interleukin (IL)-10
      and IL-5 and low levels of IL-4 and interferon-gamma (IFN-gamma). Here, we
      demonstrate that immunization with antigen in the presence of CT induced a
      population of antigen-specific CD4(+) T cells that produced IL-10 in the absence
      of IL-4, in addition to cells that coexpressed IL-4 and IL-10 or produced IL-4
      only. CT-generated Tr1 cells inhibited antigen-specific proliferation as well as
      IFN-gamma production by Th1 cells, and this suppression was cell contact
      independent. It is interesting that coincubation with Th1 cells significantly
      enhanced IL-10 production by the Tr1 cells. As IL-10 can promote the
      differentiation of Tr1 cells, we investigated cytokine production by dendritic
      cells (DC) following exposure to CT. Previous data showed that CT can modulate
      the expression of costimulatory molecules and inhibit the production of
      chemokines and cytokines, including IL-12 and tumor necrosis factor alpha and
      enhance IL-10 production. Here, we show that CT synergizes with LPS to induce IL
      6 and IL-1beta in addition to IL-10 production by immature DC. Therefore, CT may
      promote the induction of Th2 and Tr1 cells in part via selective modulation of DC
      cytokine production and costimulatory molecule expression.

PMID- 14704374
TI  - Effects of gestational and lactational exposure to organochlorine compounds on
      cellular, humoral, and innate immunity in swine.
AB  - Few studies have characterized the immunotoxic potential of complex mixtures of
      organochlorines (OCs) that bear environmental relevance. We monitored immune
      parameters in male piglets exposed in utero and through lactation to an OC
      mixture which was designed to approximate that found in the traditional diet of
      Arctic aboriginal populations. Prepubertal sows were administered orally either
      corn oil (control group) or the OC mixture in increasing doses (low, medium, and
      high). The sows were inseminated with the semen from an untreated boar and OC
      treatment was continued throughout gestation and lactation (21 days). Blood was
      collected from the sows at delivery and monthly from piglets until 8 months of
      age for the determination of plasma OC concentrations and parameters of innate,
      cellular, and humoral immunity. Treatment with the OC mixture had no dose
      dependent effect on the proportion of CD4+ and CD8+ T-cell subsets, and did not
      modulate the functional activity of the complement component C2. The proportion
      of CD4+CD8+ cells, CD8+DR+ cells, and the mitogenic lymphoproliferative response
      increased in OC-treated, 4-month-old piglets. At 6 months, the
      lymphoproliferative response to mitogen and the proportion CD4+CD8+ cells were
      still elevated in the OC-treated piglets, but the proportion of CD8+DR+ cells was
      decreased as compared to the controls. Animals in the high-dose group also
      exhibited a slight increase in polymorphonuclear leukocyte phagocytic activity at
      8 months of age. Furthermore, the high dose decreased the antibody response to
      Mycoplasma hyopneumoniae. Our results indicate that developmental exposure to an
      environmentally relevant OC mixture alters the immune function in swine.

PMID- 14704375
TI  - The effects of perinatal tebuconazole exposure on adult neurological,
      immunological, and reproductive function in rats.

PMID- 14704376
TI  - Self, society, and the "new gerontology".
AB  - The "new gerontology," built on the concept of successful aging, sets forth the
      preconditions for and the end product of the process of aging successfully.
      Focused on health and active participation in life, it vests largely within
      individuals the power to achieve this normatively desirable state. While
      acknowledging the contributions of the scientific base for Rowe and Kahn's
      successful aging model, we emphasize the need for a more careful examination of
      the model itself. Using critical gerontology as a primary filter, we critique
      this normative vision by focusing on its unarticulated (and perhaps unexplored)
      values, assumptions, and consequences. We argue that these unexamined features
      may further harm older people, particularly older women, the poor, and people of
      color who are already marginalized. We conclude by suggesting forms of resistance
      to this univocal standard.

PMID- 14704377
TI  - Case management: effects of improved risk and value information.
AB  - PURPOSE: The purpose of this study was to determine the impact on resource use of
      providing case managers with information on the potential for patients to benefit
      from home care services. DESIGN AND METHODS: Twenty-four case managers working in
      the Arizona Long Term Care System (ALTCS) were randomized into treatment and
      control groups. Members of the treatment group were given patient assessments for
      25 ALTCS clients, estimates of the patients' risks for various adverse outcomes,
      and estimates of the aggregate potential benefit for each patient. Members of the
      control group were given only patient assessments (as is usual practice) for the
      same sample of 25 clients. Both groups were asked to independently write
      nonbinding care plans for each patient. The cost of each case manager's care
      plans was computed by multiplying standard costs per service times the mix and
      volume of services prescribed for each patient. RESULTS: Treatment group care
      plan costs were, on average, lower than control group costs and closely tracked
      variation in estimated patient risks. Comparison group care plan costs were
      unrelated to risks. IMPLICATIONS: Information about risk and potential benefit
      can improve targeting of services to long-term-care clients. A prospective study
      using such an approach is warranted to see if provision of risk and potential
      benefit information would produce better clinical and economic outcomes.

PMID- 14704378
TI  - Verve not ERVs for care planners.

PMID- 14704380
TI  - Two models of caregiver strain and bereavement adjustment: a comparison of
      husband and daughter caregivers of breast cancer hospice patients.
AB  - PURPOSE: Caregiver bereavement adjustment literature suggests opposite models of
      impact of role strain on bereavement adjustment after care-recipient death-a
      Complicated Grief Model and a Relief Model. This study tests these competing
      models for husband and adult-daughter caregivers of breast cancer hospice
      patients. DESIGN AND METHODS: This study used secondary data from the National
      Hospice Study ( Greer & Mor, 1987). Stepwise multiple regression analyses, using
      caregiver's age and two formulations of prebereavement caregiver role strain as
      independent variables, predicted grief and despair bereavement adjustment as
      dependent variables. RESULTS: Data from husbands supported a Complicated Grief
      Model, as greater empirically derived (anxiety and depression symptoms) and
      theoretically derived (psychological and health strain) caregiver role strain
      formulations both predicted more difficult bereavement adjustment for husbands.
      Neither model was supported for adult daughters, as neither formulation of
      caregiver role strain predicted daughters' bereavement adjustment. Older
      caregiver age predicted better bereavement adjustment for both husbands and
      daughters. Adult daughters experienced more caregiver role strain than husbands
      did. IMPLICATIONS: The family role relationship between caregiver and patient
      (husband-wife vs. daughter-mother relationship) affects how caregiving factors
      influence bereavement adjustment.

PMID- 14704381
TI  - Caregiver stress and noncaregiver stress: exploring the pathways of psychiatric
      morbidity.
AB  - PURPOSE: This study examines depressive symptoms among adult children of elderly
      parents; it views the parents' care needs and child's care activities as two
      separate stressors, different combinations of which may affect both caregiving
      and noncaregiving family members. DESIGN AND METHODS: A sample of 4,380 women and
      3,965 men from the first wave of the Health and Retirement Study was analyzed by
      use of four alternative forms of multiple regression analysis. Using the Center
      for Epidemiological Studies Depression scale, respondents reported on their
      depressive symptoms, as well as on parental disability and care provided by
      themselves, their spouses, and siblings. RESULTS: Noncaregivers reporting severe
      parental disability were significantly more likely to experience depression
      symptoms. Evidence of increased manifestations of depression was not found among
      those caring for severely disabled relatives; nor was it found among those
      providing care in the absence of severe parental care needs. Having a caregiving
      sibling was associated with increased CES-D scores among noncaregivers.
      IMPLICATIONS: In the current literature, personal care needs of a close relative
      are named among significant disturbances in the lives of caregivers. By extending
      this approach to members of a family network regardless of caregiver status, this
      study allows us to distinguish the magnitude of negative outcomes of serious
      parental care needs while clarifying the impact uniquely attributable to
      caregiving activities.

PMID- 14704382
TI  - Setting priorities for gerontological social work research: a national Delphi
      study.
AB  - PURPOSE: An increasingly important task for all disciplines involved in aging
      research is to identify and prioritize areas for investigation. This article
      reports the results of a national Delphi study on setting research priorities for
      gerontological social work. DESIGN AND METHODS: Delphi methodology, a structured
      process for eliciting and correlating informed opinions from a panel of experts
      on a specific topic, was used. A national expert panel of 46 gerontological
      social workers completed three successive Web-based questionnaires with
      controlled feedback to delimit a set of high-priority research topics. RESULTS:
      There were 49 independent research topics identified, 16 of which attained high
      or highest priority and high or moderate consensus ratings. The top-priority
      topic was developing and testing psychosocial interventions across specific
      populations and conditions. Three additional topics on intervention research
      achieved similar ratings, as did all four topics on services research.
      IMPLICATIONS: The research priorities identified by expert panelists in this
      study represent critical knowledge needs for the social work profession in aging,
      and they overlap and complement the current research agendas of the National
      Research Council and the National Institute on Aging. They are thus expected to
      help guide the development and prioritization of social work and
      interdisciplinary research to improve practice and policies affecting older
      adults and their families.

PMID- 14704383
TI  - Sentence completion to assess children's views about aging.
AB  - PURPOSE: Sentence completion exercises require students to give open-ended
      responses to prompts. The first purpose of this article is to describe the method
      of sentence completion to assess middle-school children's attitudes and beliefs
      about aging. The second purpose is to describe the patterns of characteristics
      that children associate with aging. DESIGN AND METHODS: Two middle schools in San
      Antonio, TX agreed to have their students participate in the sentence completion
      exercises at the beginning of the 1998-1999 school year. Teachers asked students
      to write responses to the following prompts: "Old is.," "You know you are old
      when.," "You know your parents are old when.," "When I am old, I.," and "Old
      people." We coded the responses for their characteristics and whether they were
      positive, negative, or neutral. RESULTS: Of the 2,476 students, 1,874 (75.6%)
      wrote responses to at least one prompt. Overall, we collected 3,700 responses and
      coded 9,438 characteristics (2.6 characteristics per response). The most common
      characteristics of aging were having wrinkles (21.1%), having gray hair or being
      bald (20.0%), and being less active (17.5%). Students had a much more positive
      view of their future (55.4%) compared with their view of aging elicited by the
      other prompts (range of 4.9-25.7% positive responses). Students infrequently
      associated old age with specific conditions; only 4.6% mentioned diseases, 6.0%
      mentioned being ill or taking medications, and 5.7% mentioned sensory problems.
      IMPLICATIONS: Middle-school students view their futures much more positively than
      the changes they observe in their parents and other elders. Students infrequently
      identified specific diseases or impairments as responsible for the changes they
      observe with aging. These observed responses provide a starting point for
      educators to develop and deliver gerontologically based materials that teach
      about healthful habits to maintain independence across a life span.

PMID- 14704384
TI  - Relating medical students' knowledge, attitudes, and experience to an interest in
      geriatric medicine.
AB  - PURPOSE: This study examined medical students' interest in geriatrics: Are
      knowledge, positive attitudes, and prior experience with older adults associated
      with an interest in geriatric medicine? DESIGN AND METHODS: Entering University
      of Michigan medical students completed three surveys: the Revised Facts on Aging
      Quiz, the University of California at Los Angeles Geriatric Attitudes Scale, and
      the Maxwell-Sullivan Attitudes Scale. The students were also asked questions
      about their prior experience with older adults and their interest in geriatric
      medicine. RESULTS: The results indicate that incoming medical students have
      minimal knowledge about aging, moderately positive attitudes toward older adults,
      and low interest in geriatric medicine. Having more positive attitudes toward
      older adults (ss =.28) and having cared for older persons prior to medical school
      (ss =.14) were associated with greater interest in geriatric medicine.
      IMPLICATIONS: These findings suggest that interventions to increase the number of
      geriatric-oriented physicians should focus on influencing learners' attitudes
      through experiences in the care of older adults.

PMID- 14704385
TI  - Self-reported health among older Bangladeshis: how good a health indicator is it?
AB  - PURPOSE: This study examines the value of self-reported health (SRH) as an
      indicator of underlying health status in a developing country setting. DESIGN AND
      METHODS: Logistic regression methods with adjustments for multistage sampling are
      used to examine the factors associated with SRH in 2,921 men and women aged 50
      and older in rural Bangladesh. RESULTS: SRH incorporates multiple dimensions of
      health status (including physical disability assessed by measured physical
      performance; self-reported limitations in activities of daily living, or ADLs;
      self-reported chronic morbidity; and self-reported acute morbidity), severity,
      comorbidity, and trajectory in a similar fashion for both men and women and for
      different age groups. Older individuals are more likely to report poor SRH than
      their younger counterparts, and women report significantly worse SRH than their
      male peers at each age group. In both cases, this disadvantage can be fully
      accounted for by differences in measured physical performance, ADL limitations,
      and chronic and acute morbidity. IMPLICATIONS: Among older Bangladeshis, SRH is
      an easily recorded, multifaceted, nuanced indicator of underlying health status
      that is significantly associated with measured physical performance. Moreover,
      SRH appears to be independent of age- and gender-related norms.

PMID- 14704386
TI  - Health-seeking behaviors of elderly Chinese Americans: shifts in expectations.
AB  - PURPOSE: This study reported a qualitative analysis of health-seeking behaviors
      of community-dwelling elderly Chinese Americans on the influences of family
      network, cultural values, and immigrant experience in their use of health
      resources. Barriers to health care, pathway of health care, and adaptation of
      health care by use of self-treatment and Eastern and Western medicines were also
      examined. DESIGN AND METHODS: The investigators used content analysis to obtain
      themes and key points of focus group interview data (N = 25) to explore the
      elderly participants' attitudes, values, and practices in their use of health
      resources. Survey questionnaires in Chinese were used to compile demographic
      data. RESULTS: Findings suggested a shift from traditional expectations of filial
      piety to more dependence on neighbors and friends, and a genuine adaptability to
      combining Eastern and Western health care modalities. Immigration was not
      proposed by these Chinese elders as an explanation of shifts in expectations for
      family support or values. IMPLICATIONS: This study has implications for research,
      service delivery, and policy making for health care of ethnic elderly persons,
      particularly in addressing structural and cultural issues in access and
      compliance.

PMID- 14704387
TI  - A national survey of assisted living facilities.
AB  - PURPOSE: Throughout the 1990s, assisted living was the most rapidly growing form
      of senior housing. The purpose of this paper is to describe the existing supply
      of assisted living facilities (ALFs) and examine the extent to which they matched
      the philosophy of assisted living. DESIGN AND METHODS: The study involved a
      multistage sample design to produce nationally representative estimates for the
      ALF industry. Administrators of nearly 1,500 eligible ALFs were interviewed by
      telephone. RESULTS: As of 1998, there were an estimated 11,459 ALFs nationwide,
      with 611,300 beds and 521,500 residents. Nearly 60% offered a combination of low
      services and low or minimal privacy, whereas only 11% offered relatively high
      services and high privacy. Seventy-three percent of the resident rooms or
      apartments were private. Aging-in-place was limited by discharge policies in most
      ALFs for residents who needed help with transfers, had moderate to severe
      cognitive impairment, had any behavioral symptoms, or needed nursing care. The
      industry is largely private pay and unaffordable for low- or moderate-income
      persons aged >/=75 unless they use assets as well as income to pay. IMPLICATIONS:
      ALFs differed widely in ownership, size, policies, and the degree to which they
      manifested the philosophy of assisted living. This diversity represents a
      challenge for consumers in terms of selecting an appropriate facility and for
      policy makers in terms of deciding what role they want assisted living to play in
      long-term care.

PMID- 14704388
TI  - Consumer satisfaction in long-term care: state initiatives in nursing homes and
      assisted living facilities.
AB  - PURPOSE: We report the results of a survey of state initiatives that measure
      resident satisfaction in nursing homes and assisted living facilities, and we
      describe several model programs for legislators and public administrators
      contemplating the initiation of their own state programs. DESIGN AND METHODS:
      Data on state initiatives and programs were collected during March and April 2000
      through a mailed questionnaire and follow-up telephone interviews and were
      current as of September 2002. RESULTS: Of the 50 states surveyed, 50 responses
      were received (response rate = 100%); 12 states (24%) reported the use of
      consumer satisfaction measures, and 7 (Florida, Iowa, Ohio, Oregon, Texas,
      Vermont, and Wisconsin) reported using resident satisfaction data within their
      consumer information systems for nursing homes or assisted living facilities.
      Additionally, 2 states (Iowa and Wisconsin) use resident satisfaction data for
      facility licensing and recertification. The design of the instruments and
      collection methods vary in these states, as do the reported response rates, per
      resident cost, and the purpose for satisfaction data collection. IMPLICATIONS:
      State satisfaction efforts are in an early stage of development. Well-produced,
      easily understandable reports on nursing home and assisted living quality could
      provide information and guidance for patients and families contemplating the
      utilization of long-term care services. Dissemination of quality information may
      also facilitate sustained quality and efficiency improvements in long-term care
      facilities and thus enhance the quality of care for and quality of life of long
      term care residents.

PMID- 14704389
TI  - Economic consequences of retiree concentrations: a review of North American
      studies.
AB  - PURPOSE: The study of patterns of residential mobility among individuals around
      the age of retirement has led to the recognition that for many reasons-climate
      and cost of living being the most frequently cited-settlement patterns of
      comparatively affluent retirees will often differ from those of the working-age
      population. Increasingly, localities may often seek this type of relocation, on
      the theory that the newcomers will provide a boost to the local economy through
      expenditures and tax payments. In addition, there is often the perception that
      such a strategy will not cost the community much in the way of locally provided
      public services. The past several years have witnessed a substantial increase in
      efforts to provide some quantitative estimates on the magnitude of these
      hypothetical effects. DESIGN AND METHODS: This article aims at providing a
      summary assessment of such analyses, incorporating research projects in both the
      United States and Canada. RESULTS: Practically all such studies may be
      characterized as being exclusively short term in nature; that is, they focus more
      or less exclusively on the near-term implications of retiree inmigration, which
      do tend to be overwhelmingly positive from an economic or fiscal perspective.
      IMPLICATIONS: In general, this area of inquiry may be characterized by a paucity
      of knowledge regarding the longer term effects of such population movement. There
      has been no effort to analyze the aging in place of the erstwhile newcomers or
      the failure of the retirement migration process to generate other than a plethora
      of opportunities for comparatively low-skill, low-wage service employment.
      Policies intended to foster amenity migration as an economic development tool
      would greatly benefit from longer term analyses of the economic implications of
      the process.

PMID- 14704390
TI  - A first look at retirement migration trends in 2000.
AB  - PURPOSE: This brief report takes a look at the preliminary estimates of the
      number and proportion of migrants over the age of 60 who moved to and from states
      between 1995 and 2000 and compares these estimates with those who made the same
      kind of move one decade earlier. DESIGN AND METHODS: The 2000 census 1-in-100
      public-use microdata sample, released in the summer of 2003, and the 1-in-20
      sample from the 1990 census, were compared in this analysis. Point estimates of
      100% were created for the inflows and outflows for the top 10 states in these two
      census decades. Net migration was also considered. RESULTS: The total estimated
      number of older interstate migrants increased to over 2 million during the 1995
      2000 migration period. Florida declined slightly in its position as the dominant
      destination for a second decade, indicating a downward trend for the first time.
      Arizona became the second largest receiving state, next to Florida, and
      California approached New York's dominance as a migration origin, or sending,
      state. Nevada entered the top ranking retirement states for the first time.
      IMPLICATIONS: Long-term migration dynamics of the older population may reflect
      perceived shifts in quality of life in destination states. Nonetheless, the next
      two decades will see a substantial rise in the number of older migrants.

PMID- 14704391
TI  - The savvy caregiver program: developing and testing a transportable dementia
      family caregiver training program.
AB  - PURPOSE: This article reports on the development and field testing of the Savvy
      Caregiver Program, the transformation of a successful, academic-based caregiver
      psychoeducational program into a self-contained program that can be adopted in
      other locations. DESIGN AND METHODS: Program development began with a prototype
      of a 12-hr course with the aims of introducing family caregivers to the
      caregiving role, providing them with the knowledge, skills, and attitudes needed
      to carry out that role, and alerting them to self-care issues. Results from
      initial field trials dictated a substantial revision of the workshop materials.
      The next version was field tested in multiple sites in southern rural Minnesota,
      Colorado, and Alaska. In this expanded testing, participants evaluated the
      program, and cross-group comparisons were conducted by use of well-established
      caregiver well-being scales. RESULTS: Virtually all respondents reported
      increased skill, knowledge, and confidence, and all would recommend the program
      to others. A preintervention versus postintervention analysis indicates that
      caregivers' reaction to the overall behavior of the persons for whom they provide
      care (i.e., "total reaction"), their self-reported burden, and their beliefs
      about caregiving (emotional enmeshment) changed significantly in directions
      indicating better caregiver well-being. IMPLICATIONS: Results suggest that it is
      feasible to translate a research-based caregiver intervention into a packaged
      program that can be adopted in other settings without the direct involvement of
      the program initiators.

PMID- 14704392
TI  - Evaluating a practice-oriented service model to increase the use of respite
      services among minorities and rural caregivers.
AB  - PURPOSE: The goal of this study was to evaluate the practice-oriented model of
      service use (Yeatts, Crow, & Folts, 1992) relative to the more widely used
      behavioral model ( Andersen, 1968) in its ability to explain the use of respite
      services by caregivers of Alzheimer's patients. Unlike the behavioral model,
      which focuses primarily on characteristics of the service user, the practice
      oriented model focuses primarily on characteristics of the service. DESIGN AND
      METHODS: Interview data from 1,158 caregivers participating in the Alzheimer's
      Disease Demonstration Grants to States program ( Montgomery, Kosloski, Karner, &
      Schaefer, 2002) were analyzed. Separate regression models were estimated for
      adult day care and in-home respite, using the full information maximum likelihood
      procedure described by Arbuckle (1996), and ordinary least squares regression
      with listwise deletion of missing data. RESULTS: The findings indicate that the
      factors related to respite use tapped by the practice-oriented model add
      significantly to explanatory models of service use over models that use only the
      factors typically represented by the behavioral model. Additional analyses,
      including a set of interactions with ethnicity, indicated that this improvement
      occurs primarily for White and Hispanic caregivers, and less so for African
      Americans. IMPLICATIONS: The findings are discussed in terms of their
      implications for enhancing the timely use of respite services and directions for
      future research.

PMID- 14704393
TI  - Addressing health needs of an aging society through medical-religious
      partnerships: what do clergy and laity think?
AB  - PURPOSE: This article reports on the interest within the religious community in a
      medical-religious partnership model designed to address some of the health
      challenges communities face as the population continues to age and become more
      diverse. DESIGN AND METHODS: A geographically and religiously diverse group of
      183 clergy who were attending a continuing education program on theology and
      preaching were invited to complete a 16-item survey asking about their interest
      in working with hospitals to offer health-related programs and activities in
      their congregations. Another sample, this one consisting of 524 individuals from
      a religiously diverse group of congregations in Florida, was also asked about
      their interest in having health programs offered in their congregations. RESULTS:
      Of the 54% of clergy who completed the surveys, 72% said it was "very important"
      and 28% said it was "somewhat important" to actively address the health needs of
      their congregations. Support for specific programs was also strong, with at least
      80% reporting it was very likely they would support screenings, preventive
      interventions, and health-related classes in their congregations. Strong support
      was also found among the laity surveyed, with 85% expressing interest in faith
      based health programs and 45% reporting they would be interested in helping
      organize and promote such programs. IMPLICATIONS: Health care systems and other
      organizations interested in addressing health needs of older adults can look to
      religious institutions for assistance in providing the information and support
      patients and family members need to prevent or minimize the impact of chronic
      illnesses.

PMID- 14704397
TI  - Disclosure and disinterest.

PMID- 14704398
TI  - ITER. No meeting of the minds on fusion megaproject.

PMID- 14704399
TI  - Cancer research. Drug candidate bolsters cell's tumor defenses.

PMID- 14704400
TI  - European science. Momentum builds for basic research agency.

PMID- 14704401
TI  - Microbiology. The Pfiesteria conundrum: more study, less certainty.

PMID- 14704402
TI  - Infectious diseases. Second lab accident fuels fears about SARS.

PMID- 14704403
TI  - Astrophysics. Are most life-friendly stars older than the sun?

PMID- 14704404
TI  - Neuroscience. Long-term memory: a positive role for a prion?

PMID- 14704405
TI  - Scientific conduct. Charges don't stick to The Skeptical Environmentalist.

PMID- 14704406
TI  - Chemistry. Newcomer heats up the race for practical fuel cells.

PMID- 14704407
TI  - Planet hunting. The search for pale blue dots.

PMID- 14704408
TI  - Archaeology. A surprising survival story in the Siberian Arctic.

PMID- 14704409
TI  - Environment. Uncertain science underlies new mercury standards.

PMID- 14704410
TI  - Climate change. Sea change in the Atlantic.

PMID- 14704411
TI  - Counting whales in the North Atlantic.

PMID- 14704412
TI  - Research and the Bayh-Dole Act.

PMID- 14704414
TI  - Astronomy. Long gamma-ray bursts.

PMID- 14704413
TI  - Beyond the ivory tower. A distant mirror for the brain.

PMID- 14704415
TI  - Astronomy. Short gamma-ray bursts.

PMID- 14704416
TI  - Physiology. Running a-fowl of the law.

PMID- 14704417
TI  - Neuroscience. Sealing cortical cell fate.

PMID- 14704418
TI  - Plant sciences. Promiscuous maize chromosomes.

PMID- 14704419
TI  - The Yana RHS site: humans in the Arctic before the last glacial maximum.
AB  - A newly discovered Paleolithic site on the Yana River, Siberia, at 71 degrees N,
      lies well above the Arctic circle and dates to 27,000 radiocarbon years before
      present, during glacial times. This age is twice that of other known human
      occupations in any Arctic region. Artifacts at the site include a rare rhinoceros
      foreshaft, other mammoth foreshafts, and a wide variety of tools and flakes. This
      site shows that people adapted to this harsh, high-latitude, Late Pleistocene
      environment much earlier than previously thought.

PMID- 14704420
TI  - Foxg1 suppresses early cortical cell fate.
AB  - During mammalian cerebral corticogenesis, progenitor cells become progressively
      restricted in the types of neurons they can produce. The molecular mechanism that
      determines earlier versus later born neuron fate is unknown. We demonstrate here
      that the generation of the earliest born neurons, the Cajal-Retzius cells, is
      suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null
      mutants, we observed an excess of Cajal-Retzius neuron production in the cortex.
      By conditionally inactivating Foxg1 in cortical progenitors that normally produce
      deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required
      to suppress Cajal-Retzius cell fate. Hence, the competence to generate the
      earliest born neurons during later cortical development is actively suppressed
      but not lost.

PMID- 14704421
TI  - The galactic habitable zone and the age distribution of complex life in the Milky
      Way.
AB  - We modeled the evolution of the Milky Way Galaxy to trace the distribution in
      space and time of four prerequisites for complex life: the presence of a host
      star, enough heavy elements to form terrestrial planets, sufficient time for
      biological evolution, and an environment free of life-extinguishing supernovae.
      We identified the Galactic habitable zone (GHZ) as an annular region between 7
      and 9 kiloparsecs from the Galactic center that widens with time and is composed
      of stars that formed between 8 and 4 billion years ago. This GHZ yields an age
      distribution for the complex life that may inhabit our Galaxy. We found that 75%
      of the stars in the GHZ are older than the Sun.

PMID- 14704422
TI  - Supramolecular self-assembly of macroscopic tubes.
AB  - The macroscopic molecular self-assembly of an amphiphilic hyperbranched copolymer
      in acetone generated multiwalled tubes millimeters in diameter and centimeters in
      length. The thickness of the tube walls approaches 400 nanometers, and the walls
      have an inhomogeneous lamella structure that alternates between ordered
      hydrophilic domains and amorphous, partly irregular hydrophilic domains.

PMID- 14704423
TI  - Osmium isotope heterogeneity in the constituent phases of mid-ocean ridge
      basalts.
AB  - Radiogenic isotope variations in mid-ocean ridge basalts (MORB) are commonly
      attributed to compositional variations in Earth's upper mantle. For the
      rheniumosmium isotope system, constituent MORB phases are shown to possess
      exceptionally high Re/Os (parent/daughter) ratios, consequently radiogenic 187Os
      is produced from the decay of 187Re over short periods of time. Thus, in the
      absence of precise age constraints, Os isotope variations cannot be unambiguously
      attributed to their source, although Re-Os isotope data for constituent minerals
      can yield crystallization ages, details of equilibration, and initial Os isotope
      values that relate directly to the mantle source.

PMID- 14704424
TI  - Continental-scale partitioning of fire emissions during the 1997 to 2001 El
      Nino/La Nina period.
AB  - During the 1997 to 1998 El Nino, drought conditions triggered widespread
      increases in fire activity, releasing CH4 and CO2 to the atmosphere. We evaluated
      the contribution of fires from different continents to variability in these
      greenhouse gases from 1997 to 2001, using satellite-based estimates of fire
      activity, biogeochemical modeling, and an inverse analysis of atmospheric CO
      anomalies. During the 1997 to 1998 El Nino, the fire emissions anomaly was 2.1 +/
      0.8 petagrams of carbon, or 66 +/- 24% of the CO2 growth rate anomaly. The main
      contributors were Southeast Asia (60%), Central and South America (30%), and
      boreal regions of Eurasia and North America (10%).

PMID- 14704425
TI  - Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical
      enzyme.
AB  - The crystal structure of biotin synthase from Escherichia coli in complex with S
      adenosyl-L-methionine and dethiobiotin has been determined to 3.4 angstrom
      resolution. This structure addresses how "AdoMet radical" or "radical SAM"
      enzymes use Fe4S4 clusters and S-adenosyl-L-methionine to generate organic
      radicals. Biotin synthase catalyzes the radical-mediated insertion of sulfur into
      dethiobiotin to form biotin. The structure places the substrates between the
      Fe4S4 cluster, essential for radical generation, and the Fe2S2 cluster,
      postulated to be the source of sulfur, with both clusters in unprecedented
      coordination environments.

PMID- 14704426
TI  - Partitioning the energetics of walking and running: swinging the limbs is
      expensive.
AB  - Explaining the energetics of walking and running has been difficult because the
      distribution of energy use among individual muscles has not been known. We
      estimated energy use by measuring blood flow to the hindlimb muscles in guinea
      fowl. Blood flow to skeletal muscles is controlled locally and varies directly
      with metabolic rate. We estimate that the swing-phase muscles consume 26% of the
      energy used by the limbs and the stance-phase muscles consume the remaining 74%,
      independent of speed. Thus, contrary to some previous suggestions, swinging the
      limbs requires an appreciable fraction of the energy used during terrestrial
      legged locomotion. Models integrating the energetics and mechanics of running
      will benefit from more detailed information on the distribution of energy use by
      the muscles.

PMID- 14704427
TI  - A previously unknown maltose transporter essential for starch degradation in
      leaves.
AB  - A previously unknown maltose transporter is essential for the conversion of
      starch to sucrose in Arabidopsis leaves at night. The transporter was identified
      by isolating two allelic mutants with high starch levels and very high maltose,
      an intermediate of starch breakdown. The mutations affect a gene of previously
      unknown function, MEX1. We show that MEX1is a maltose transporter that is
      unrelated to other sugar transporters. The severe mex1 phenotype demonstrates
      that MEX1is the predominant route of carbohydrate export from chloroplasts at
      night. Homologous genes in plants including rice and potato indicate that maltose
      export is of widespread significance.

PMID- 14704428
TI  - Coordination of meiotic recombination, pairing, and synapsis by PHS1.
AB  - Pairing, synapsis, and recombination are prerequisites for accurate chromosome
      segregation in meiosis. The phs1 gene in maize is required for pairing to occur
      between homologous chromosomes. In the phs1 mutant, homologous chromosome
      synapsis is completely replaced by synapsis between nonhomologous partners. The
      phs1 gene is also required for installation of the meiotic recombination
      machinery on chromosomes, as the mutant almost completely lacks chromosomal foci
      of the recombination protein RAD51. Thus, in the phs1 mutant, synapsis is
      uncoupled from recombination and pairing. The protein encoded by the phs1 gene
      likely acts in a multistep process to coordinate pairing, recombination, and
      synapsis.

PMID- 14704429
TI  - Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome
      domains.
AB  - Interactions between ends from different DNA double-strand breaks (DSBs) can
      produce tumorigenic chromosome translocations. Two theories for the juxta
      position of DSBs in translocations, the static "contact-first" and the dynamic
      "breakage-first" theory, differ fundamentally in their requirement for DSB
      mobility. To determine whether or not DSB-containing chromosome domains are
      mobile and can interact, we introduced linear tracks of DSBs in nuclei. We
      observed changes in track morphology within minutes after DSB induction,
      indicating movement of the domains. In a subpopulation of cells, the domains
      clustered. Juxtaposition of different DSB-containing chromosome domains through
      clustering, which was most extensive in G1 phase cells, suggests an adhesion
      process in which we implicate the Mre11 complex. Our results support the breakage
      first theory to explain the origin of chromosomal translocations.

PMID- 14704430
TI  - Coordinated activation of Hsp70 chaperones.
AB  - Hsp70s are a ubiquitous family of molecular chaperones involved in many cellular
      processes. Two Hsp70s, Lhs1p and Kar2p, are required for protein biogenesis in
      the yeast endoplasmic reticulum. Here, we found that Lhs1p and Kar2p specifically
      interacted to couple, and coordinately regulate, their respective activities.
      Lhs1p stimulated Kar2p by providing a specific nucleotide exchange activity,
      whereas Kar2p reciprocally activated the Lhs1p adenosine triphosphatase (ATPase).
      The two ATPase activities are coupled, and their coordinated regulation is
      essential for normal function in vivo.

PMID- 14704431
TI  - A map of the interactome network of the metazoan C. elegans.
AB  - To initiate studies on how protein-protein interaction (or "interactome")
      networks relate to multicellular functions, we have mapped a large fraction of
      the Caenorhabditis elegans interactome network. Starting with a subset of
      metazoan-specific proteins, more than 4000 interactions were identified from high
      throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity
      purification assays experimentally validated the overall quality of this Y2H data
      set. Together with already described Y2H interactions and interologs predicted in
      silico, the current version of the Worm Interactome (WI5) map contains
      approximately 5500 interactions. Topological and biological features of this
      interactome network, as well as its integration with phenome and transcriptome
      data sets, lead to numerous biological hypotheses.

PMID- 14704434
TI  - HPLC of peptides and proteins: basic theory and methodology.

PMID- 14704432
TI  - In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
AB  - MDM2 binds the p53 tumor suppressor protein with high affinity and negatively
      modulates its transcriptional activity and stability. Overexpression of MDM2,
      found in many human tumors, effectively impairs p53 function. Inhibition of MDM2
      p53 interaction can stabilize p53 and may offer a novel strategy for cancer
      therapy. Here, we identify potent and selective small-molecule antagonists of
      MDM2 and confirm their mode of action through the crystal structures of
      complexes. These compounds bind MDM2 in the p53-binding pocket and activate the
      p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth
      inhibition of human tumor xenografts in nude mice.

PMID- 14704435
TI  - Reversed-phase high-performance liquid chromatography.

PMID- 14704433
TI  - RNAi-mediated targeting of heterochromatin by the RITS complex.
AB  - RNA interference (RNAi) is a widespread silencing mechanism that acts at both the
      posttranscriptional and transcriptional levels. Here, we describe the
      purification of an RNAi effector complex termed RITS (RNA-induced initiation of
      transcriptional gene silencing) that is required for heterochromatin assembly in
      fission yeast. The RITS complex contains Ago1 (the fission yeast Argonaute
      homolog), Chp1 (a heterochromatin-associated chromodomain protein), and Tas3 (a
      novel protein). In addition, the complex contains small RNAs that require the
      Dicer ribonuclease for their production. These small RNAs are homologous to
      centromeric repeats and are required for the localization of RITS to
      heterochromatic domains. The results suggest a mechanism for the role of the RNAi
      machinery and small RNAs in targeting of heterochromatin complexes and epigenetic
      gene silencing at specific chromosomal loci.

PMID- 14704436
TI  - Ion-exchange chromatography.

PMID- 14704437
TI  - High-performance hydrophobic interaction chromatography.

PMID- 14704438
TI  - Gel filtration chromatography.

PMID- 14704440
TI  - Immobilized metal ion affinity chromatography of proteins.

PMID- 14704439
TI  - Hydrophilic interaction chromatography.

PMID- 14704441
TI  - Immunoaffinity chromatography of proteins.

PMID- 14704442
TI  - Liquid chromatography-mass spectrometry and tandem mass spectrometry of peptides
      and proteins.

PMID- 14704443
TI  - Capillary separations.

PMID- 14704444
TI  - Micropreparative HPLC of peptides and proteins.

PMID- 14704445
TI  - Multidimensional HPLC purification of proteins.

PMID- 14704446
TI  - Analytical high-performance liquid chromatography.

PMID- 14704447
TI  - Prep/Semiprep separations of peptides.

PMID- 14704448
TI  - Large-scale protein chromatography.

PMID- 14704449
TI  - Proteolytic peptide mapping.

PMID- 14704450
TI  - Mass spectrometric characterization of posttranslationally modified proteins-
      phosphorylation.

PMID- 14704451
TI  - Analyses of glycopeptides and glycoproteins by liquid chromatography-mass
      spectrometry and liquid chromatography-tandem mass spectrometry.

PMID- 14704452
TI  - HPLC in the analysis of peptide metabolism.

PMID- 14704453
TI  - Isolation and characterization of naturally processed MHC-bound peptides from the
      surface of antigen-presenting cells.

PMID- 14704454
TI  - Australian funnel-web spider venom analyzed with on-line RP-HPLC techniques.

PMID- 14704455
TI  - HPLC and mass spectrometry of intrinsic membrane proteins.

PMID- 14704456
TI  - IgG purification.

PMID- 14704457
TI  - DNA-binding proteins: LC-MS to identify key domains in RNA polymerase-promoter
      interactions.

PMID- 14704458
TI  - Sensitive enzymatic analysis of histidine decarboxylase using HPLC.

PMID- 14704459
TI  - Automated vs manual profiling of peptide libraries by mass spectrometry.

PMID- 14704460
TI  - Proteome analysis.

PMID- 14704461
TI  - Role of glucocorticoids in the regulation of dopaminergic neurotransmission.
AB  - Several lines of evidence indicate that exposure to various types of stressors,
      or stress hormones may increase or induce sensitization to psychostimulants or
      enhance susceptibility of experimental animals to the effects of abusing
      substances. In order to find out what is a biological substrate of the above
      phenomenon, we investigate the impact of stress hormones on the dopaminergic
      neurotransmission. It is postulated, first, that corticosterone, an important
      stress hormone, regulates the dopaminergic neurotransmission at the level of
      dopamine D-1 receptors. Secondly, corticosterone may enhance the dopaminergic
      tone by the alterations in the synthesis of tyrosine hydroxylase, however, it is
      also conceivable that, alternatively, corticosterone may evoke translocation of
      that enzyme from the cell bodies of dopaminergic neurons to their terminals.
      Finally, arguments that dopamine D-1 receptors might regulate the release of
      corticosterone by activation of neurons in the paraventricular nucleus of
      hypothalamus are discussed.

PMID- 14704462
TI  - Perspectives of losigamone in epilepsy treatment.
AB  - Patients with drug resistant epilepsy represent about 40% of the whole population
      of epileptic patients. These patients require more than one antiepileptic drug.
      In animal models of epilepsy, it is possible to determine which combinations
      produce supra-additive anticonvulsive effects with minimal or even no adverse
      reactions. The experimental data can be helpful for predicting effective drug
      combinations in patients with refractory epilepsy. Losigamone is a new
      antiepileptic drug with an unknown mechanism of action. The drug belongs to the
      group of beta-methoxy-butenolides, and exists as a racemic mixture of two
      enantiomers (AO-242 and AO-294). The drug is eliminated by oxidation. Cytochrome
      CYP2A6 appears to be the main isoenzyme responsible for the metabolism of
      losigamone. In vitro, losigamone exerts anticonvulsant activity in the picrotoxin
      model in CA1 and CA3 hippocampal areas, the low Ca(2+) model in CA1 area and the
      low Mg(2+) model in the entorhinal cortex and hippocampus. In vivo, the drug
      exhibits significant efficacy against maximal electroshock-induced seizures in
      rodents and pentetrazole-induced clonic convulsions in mice. Potency of
      losigamone varies with the respective seizure test, animal species used in
      experiments and route of drug administration. Toxicity studies do not indicate
      any teratogenic risk of the drug, at least in animals. In clinical trial,
      losigamone proved to have satisfactory effectiveness and good tolerance in the
      treatment of partial and secondary generalized seizures. The enantiomer AO-242
      seems to be more potent than AO-294 or racemate.

PMID- 14704463
TI  - Zonisamide: a new antiepileptic drug.
AB  - Although the significant progress in pharmacotherapy of epilepsy during last
      decade was achieved, about one third of patients are resistant to the current
      treatment. When the monotherapy is not efficient, the polytherapy should be
      applied. Zonisamide (ZNS) is a new antiepileptic drug (AED) efficient in treating
      refractory epilepsy. Its efficacy in different types of seizures was confirmed in
      various animal studies as well as in clinical conditions. ZNS inhibits voltage
      dependent Na(+) channels and Ca(2+) channels of T-type. The drug influences also
      monoamine neurotransmission and exhibits free radical scavenging properties. ZNS
      has a linear and favorable pharmacokinetics with excellent oral bioavailability.
      Furthermore, ZNS treatment, compared to other anticonvulsants, is relatively safe
      and well tolerated. Since ZNS is often used in polytherapy, its interactions with
      other AEDs seem to be of particular importance. However, the experimental data
      are rather inconsistent and further studies are necessary to elucidate exact
      effects of coadministration of ZNS with other AEDs. Recently, the clinical and
      experimental studies have suggested some new indications for ZNS administration,
      as mania, neuropathic pain, Parkinson's disease or migraine prophylaxis.
      Nowadays, it is also well established that ZNS exerts neuroprotective properties.

PMID- 14704464
TI  - Remacemide--a novel potential antiepileptic drug.
AB  - Epilepsy belongs to common diseases of the brain. It affects approximately 1% of
      the population. The aim of epilepsy therapy is to keep the patient free of
      seizures without interfering with normal brain function. Unfortunately, about 30%
      of all epilepsies remain without control. In this situation patients require
      polytherapy which is usually a combination of antiepileptic drugs (AEDs) acting
      via different mechanisms of action. Many potential AEDs have been developed but
      the proportion of patients failing to respond to drug treatment has not been
      fundamentally changed. The aim of this review was to assemble current literature
      data on remacemide, a novel AED, which is suggested for the treatment of
      epilepsy. Remacemide hydrochloride is a low-affinity NMDA receptor blocker as
      well as Na(+) fast-channel blocker. The drug exerts anticonvulsant activity both
      in various animal seizure models and in clinical studies. In addition to its
      antiseizure properties, the drug seems to provide neuroprotection. Remacemide
      holds promise to serve as neuroprotectant not only in seizures but perhaps in
      other neurodegenerative conditions in humans as well.

PMID- 14704465
TI  - Anthocyanins in medicine.
AB  - Anthocyanins belong to water-soluble plant pigments. They are derivatives of 2
      phenylbenzopyrylium. Due to the common occurrence (among others in fruit) they
      are components of human diet. Owing to scientific research they have become not
      only food products but also therapeutic agents. They exhibit, among others,
      antioxidative and anti-inflammatory activity, they also show favorable effect in
      the treatment of some types of neoplasms.

PMID- 14704466
TI  - A competitive antagonist of NMDA receptors CGP 40116 attenuates experimental
      symptoms of schizophrenia evoked by MK-801.
AB  - In the present study, the interaction between a noncompetitive [(+)-MK-801] and a
      competitive (CGP 40116) NMDA receptor antagonists was tested in two different
      behavioral paradigms: locomotor activity test and prepulse inhibition of the
      acoustic startle reflex. Additionally, their effects on working memory and
      selective attention were evaluated in the delayed alternation task. All above
      paradigms served to model the symptoms of schizophrenia. It was found that
      locomotor stimulatory effect of (+)-MK-801 (0.4 mg/kg) was antagonized by prior
      administration of CGP 40116 (5 mg/kg). Lower doses of CGP 40116 (1.25 and 2.5
      mg/kg) were ineffective. CGP 40116 given alone did not influence locomotor
      activity in rats. It was also shown that CGP 40116 antagonized the disruption of
      the process of sensorimotor gating evoked by (+)-MK-801. On the contrary, both
      CGP 40116 and (+)-MK-801 increased a number of errors in the delayed alternation
      test revealing detrimental effect of CGP 40116 on spatial working memory and
      selective attention even at a lower dose than that required to antagonize the
      effects of (+)-MK-801. The presented results indicate that noncompetitive and
      competitive NMDA receptor antagonists, when used at relatively low doses, may
      produce qualitatively different behavioral effects, as evidenced by the
      experiments with locomotor activity and prepulse inhibition. Moreover, the
      competitive NMDA receptor antagonists may even inhibit some psychotomimetic
      effects related to the noncompetitive blockade of this receptor. However,
      therapeutic potential of CGP 40116, a competitive NMDA receptor antagonist,
      should be considered with caution since in the range of doses effective against
      the psychotomimetic effects of (+)-MK-801, it impairs rats' performance in the
      delayed alternation paradigm, i.e. it worsens efficacy of working memory.

PMID- 14704467
TI  - Intravenous self-administration of morphine and cocaine: a comparative study.
AB  - The aim of the present study was to estimate differences between patterns of
      morphine and cocaine use in Sprague-Dawley rats. This was done by first
      developing a set of conditions under which both drugs would be consistently self
      administered over time. Subsequently rats were studied in groups of three, with
      only one rat actively self-administering morphine or cocaine while others two
      receiving yoked injections of either the drug or saline. With the exception of
      the 0.056, 0.1, 0.3 and 1.0 mg/kg/inj. training-dose regimens, intravenous
      (i..v.)self-administration of morphine was acquired at the dose of 0.56
      mg/kg/inj. and subsequently maintained by rats. In contrast to morphine self
      administration, rats rapidly acquired cocaine self-administration behavior at
      either the 0.3 or 0.56 injection dose and showed typical inverted U-shaped dose
      response curves with maximal responding occurring at the injection dose of 0.3
      mg/kg. With the "yoked" pairs of subjects, the rate of responding of the animal
      actually self-administering the drug was significantly higher than that of a
      paired animal which passively received injection whenever the first animal self
      administered the drug. Thus, both morphine and cocaine served as a positive
      reinforcer of self-administration behavior under the fixed ratio 5 schedule of
      reinforcement. However, the 0.56 mg/kg injection dose of morphine resulted in an
      acquisition curve that was markedly, temporally delayed relative to the injection
      dose of cocaine. Finally, cocaine maintained higher rates of responding for its
      delivery than morphine. These differences between self-administration patterns of
      morphine and cocaine may provide significant information about the nature of drug
      reinforcement and dependence.

PMID- 14704468
TI  - Effect of some convulsants on the protective activity of loreclezole and its
      combinations with valproate or clonazepam in amygdala-kindled rats.
AB  - Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled
      rats, reducing both seizure and afterdischarge durations. The combinations of
      loreclezole (2.5 mg/kg) with valproate, clonazepam, or carbamazepine (applied at
      their subprotective doses) also exhibited antiseizure effect in this test.
      However, only two first combinations occurred to be of pharmacodynamic nature.
      Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k
      8644 (the opener of L-type calcium channels) reversed the protective activity of
      loreclezole alone and its combination with valproate. On the other hand,
      bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of
      loreclezole combined with clonazepam. The results support the hypothesis that the
      protective activity of loreclezole and its combinations with other antiepileptics
      may involve potentiation of GABAergic neurotransmission and blockade of L-type of
      calcium channels.

PMID- 14704470
TI  - Deficit of endogenous kynurenic acid in the frontal cortex of rats with a genetic
      form of absence epilepsy.
AB  - The present studies sought to determine the concentrations of endogenous
      kynurenic acid (KYNA) and to measure the activity of kynurenine aminotransferases
      (KAT) I and II in the discrete brain regions of 3- and 6-month old WAG/Rij rats,
      a genetic model of absence epilepsy. Analogues experiments were performed using
      age-matched ACI rats, which served as a non-epileptic control. The age-dependent
      increase in KYNA concentration in the frontal cortex of WAG/Rij rats was
      considerably reduced in comparison to what was found in ACI rats. Consequently,
      the concentration of KYNA in the frontal cortex of epileptic rats was
      significantly lower than in non-epileptic controls. There were no such strain
      differences in other brain regions. The activities of KAT I and II also showed
      age-dependent increase with an exception for KAT II in the frontal cortex. Our
      data suggest that selective deficits of endogenous KYNA may account for increased
      excitability in the frontal cortex, which in turn may lead to the development of
      spontaneous spike-wave discharges in WAG/Rij rats.

PMID- 14704469
TI  - Influence of SIB 1893, a selective mGluR5 receptor antagonist, on the
      anticonvulsant activity of conventional antiepileptic drugs in two models of
      experimental epilepsy.
AB  - SIB 1893, a non-competitive antagonist of group I metabotropic glutamate receptor
      subtype 5, administered at doses ranging from 0.25 to 10 mg/kg, failed to
      influence pentetrazole-induced convulsions in mice. Moreover, SIB 1893 (10 and 20
      mg/kg) did not affect the protective action of valproate, ethosuximide,
      phenobarbital and clonazepam in this test. Similarly, the mGluR5 antagonist did
      not modulate the antiseizure activity of carbamazepine, diphenylhydantoin and
      phenobarbital against maximal electroshock in mice. The combined treatment of SIB
      1893 with conventional antiepileptic drugs did not lead to motor impairment. Long
      term memory disturbances were observed only in the case of the combination of SIB
      1893 with phenobarbital.

PMID- 14704471
TI  - Cyclic AMP formation in chicken brain: effect of vasoactive intestinal peptide,
      peptide histidine-isoleucine (PHI), and some PHI-related peptides.
AB  - Vasoactive intestinal peptide (chicken form; chVIP), peptide histidine-isoleucine
      (porcine and rat forms; pPHI and rPHI), D-Phe(4) derivative of porcine PHI (D
      Phe(4)-pPHI), peptide histidine-methionine (PHM; human PHI), and helodermin, were
      tested for their ability to stimulate cAMP production in [(3)H]adenine-prelabeled
      slices of chick cerebral cortex (CCx) and hypothalamus (HTh). The chVIP (0.1-3
      microM) concentration-dependently and potently stimulated cAMP production in HTh
      and CCx; the responses observed after 3 microM of chVIP were comparable to those
      produced by 0.1 microM PACAP38. Helodermin (5 microM) moderately but
      significantly stimulated cAMP formation in both HTh and CCx, whereas pPHI, rPHI,
      PHM at 5 microM concentration only weakly affected cAMP production in CCx, and
      were inactive in HTh; D-Phe(4)-pPHI was inactive in both tissues. These data
      demonstrate that chVIP, PACAP, and to a lesser extent helodermin were capable of
      potently stimulating cAMP generation in the avian central nervous system. PHI
      related peptides showed only weak or no activity, depending on the tissue.

PMID- 14704472
TI  - Physiological antagonism of angiotensin II and lipopolysaccharides in early
      endotoxemia: pharmacometric analysis.
AB  - The inhibitory effect of lipopolysaccharides (LPS) on alpha-adrenergic
      contraction is quite well known, but molecular mechanism of this inhibition is
      unclear. In the present study, the interaction between alpha-adrenoceptor and
      vasopressin receptor response, and LPS in rat tail artery was investigated using
      chemical stimulation. In the presence of LPS, noradrenaline, phenylephrine and
      arginine-vasopressin, concentration-response curves (CRCs) were shifted to the
      right with the change in maximal responses. The K(A) and K(B) values calculated
      in the presence and absence of LPS did not differ significantly. The results
      strongly suggest that LPS did not change the receptors affinity. The changes in
      the relationship between receptor occupancy and response to an agonist in the
      presence of LPS and reduction of K(A)/ED(50) value suggest reduction of receptor
      reserve. In the presence of angiotensin II (Ang II), CRCs were shifted to the
      right with significant increase in receptor reserve. Moreover, this effect was
      still present in LPS-pretreated arteries. The receptor reserve reduced by LPS
      significantly increased in the presence of Ang II. It suggests that inhibitory
      effect of LPS is partially reversible. The results strongly suggest that in early
      endotoxemia, inhibitory effect of LPS may by partially reverted by an increase in
      activity of renin-angiotensin-aldosterone system.

PMID- 14704473
TI  - Lipid profile in mice fed a high-fat diet after exogenous leptin administration.
AB  - Previous studies suggest a possible link between leptin and decreased lipid
      levels, however, the role of leptin in high-fat diet-induced hyperlipidemia
      remains unclear. The aim of our study was to evaluate the effect of administering
      leptin on plasma and tissue lipids in mice fed a high-fat diet. Feeding a high
      fat diet (2% cholesterol, 0.125% bile salts, 5% peanut oil) to four-week-old
      healthy mice for a period of 45 days, resulted in significantly elevated levels
      of plasma and tissue total cholesterol, phospholipids, free fatty acids and
      triglycerides as compared with those of the control mice. Subsequently after
      thirty days, exogenous leptin (230 microg/kg i.p.) was administered
      simultaneously with the daily dose of high-fat diet every alternate day for
      fifteen days. Leptin administration significantly reduced the levels of total
      cholesterol, phospholipids, free fatty acids and triglycerides in the plasma,
      liver, heart and kidney of both the control and high-fat diet fed mice. Moreover,
      leptin administration markedly reduced the levels of plasma LDL, VLDL and
      elevated plasma HDL and the activity of lipoprotein lipase as compared with the
      untreated control and high-fat diet fed mice. Thus, leptin administration was
      found to have a marked protective effect against hyperlipidemia and thus obesity,
      by virtue of its lipid lowering effects.

PMID- 14704474
TI  - Cardiomyocyte mitochondrial KATP channels participate in the antiarrhythmic and
      antiinfarct effects of KATP activators during ischemia and reperfusion in an
      intact anesthetized rabbit model.
AB  - Recent evidence suggests that the mitochondrial K(ATP) channels may be involved
      as a subcellular mediator in cardioprotection afforded by ischemic and
      pharmacological preconditioning by K(ATP) activators. The present study
      investigated the effects of administration of non-hypotensive doses of ATP
      sensitive K(+) channel (K(ATP)) openers, nicorandil (NIC) and pinacidil (PIN),
      and specific blockers of mitochondrial (5-hydroxydecanoate) and sarcolemmal (1-[5
      [2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methyl-thiourea, HMR
      1883) K(ATP) channels prior to and during coronary occlusion and post-ischemic
      reperfusion on survival rate, ischemia- and reperfusion-induced arrhythmias and
      myocardial infarct size in anesthetized rabbits. In Group I, myocardial ischemia
      induced arrhythmias were provoked by tightening a ligature over the left main
      coronary artery for 30 min. In Group II, arrhythmias were induced by reperfusion
      following a 20 min ligation of the same artery. Both in Group I and Group II,
      early iv administration of NIC (0.47 mg/kg), PIN (0.1 mg/kg), HMR 1883 (3
      mg/kg)/NIC and HMR 1883/PIN just prior to and during ischemia increased survival
      rate (75%, 86%, 75% and 75%, respectively, vs. 55% in the control in Group I;
      75%, 75%, 75% and 67%, respectively, vs. 50% in the control in Group II),
      significantly decreased the incidence and severity of life-threatening
      arrhythmias and significantly decreased myocardial infarct size. However, late iv
      administration of NIC or PIN just prior to reperfusion did not increase survival
      rate nor confer any antiarrhythmic or cardioprotective effects. The
      antiarrhythmic and cardioprotective effects were abolished by pretreating rabbits
      with 5-hydroxy-decanoate (5 mg/kg, iv bolus). In the present study, higher levels
      of malondialdehyde and lower levels of reduced glutathione and superoxide
      dismutase in necrotic zone of myocardium in all subgroups in Group II suggest
      little anti-free radical property of NIC and PIN. Therefore, it may be assumed
      that mitochondrial K(ATP) channel opening leads to mitochondrial generation and
      release of ROS providing for IPC and antiarrhythmic activity. The mitochondrial
      rather than sarcolemmal K(ATP) channel may represent a potential site of
      cardioprotection and antiarrhythmic activity.

PMID- 14704475
TI  - Glucose 6-phosphate dehydrogenase: in vitro and in vivo effects of dantrolene
      sodium.
AB  - In our study, effects of dantrolene sodium on glucose 6-phosphate dehydrogenase
      (G6PD) were examined in the human erythrocytes in vitro and in rat erythrocytes
      in vivo. Human erythrocyte G6PD was purified using ammonium sulfate fractionation
      and 2',5'-ADP Sepharose 4B affinity chromatography. The enzyme activity was
      determined by Beutler's method. The overall purification procedures gave the
      human G6PD having the specific activity of 97.6 EU/mg of protein, which was
      purified 9760-fold with a yield of 39%. Dantrolene sodium inhibited the enzyme
      activity under in vitro conditions and the I(50) value (drug concentration which
      produces 50% inhibition) of this drug was 0.91 mM. In vivo studies were performed
      in rats (Sprague-Dawley). Dantrolene sodium at 10 mg/kg inhibited the enzyme
      activity significantly (p < 0.05) 3 h after dosing. We conclude that dantrolene
      sodium showed inhibitory effect on G6PD activity both in vitro and in vivo.

PMID- 14704476
TI  - Altered cytokeratin expression during chemoprevention of hamster buccal pouch
      carcinogenesis by S-allylcysteine.
AB  - We examined the effect of S-allylcysteine (SAC), a water-soluble garlic
      constituent, on cytokeratin expression, a sensitive and specific marker for
      differentiation status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      hamster buccal pouch (HBP) carcinogenesis in male Syrian hamsters. Hamsters were
      divided into four groups of six animals each. Animals in group 1 were painted
      with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three
      times a week for 14 weeks. Group 2 animals were painted with DMBA as in group I,
      and in addition they received orally 200 mg/kg of SAC on days alternate to DMBA
      application. Group 3 animals received SAC as in group 2. Group 4 animals received
      neither DMBA nor SAC and served as the control. The hamsters were killed after an
      experimental period of 14 weeks. Cytokeratin expression was detected by Western
      blot analysis using monoclonal antibodies AE1 and AE3. In DMBA-induced HBP
      tumors, the decreased expression of high molecular weight cytokeratins of
      molecular mass between 55-70 kDa was observed. Administration of SAC (200 mg/kg)
      to animals painted with DMBA suppressed the incidence of DMBA-induced carcinomas
      and was associated with restoration of normal cytokeratin expression. The results
      of the present study suggest that inhibition of HBP tumorigenesis by SAC may be
      due to its regulatory effects on differentiation, tumor invasiveness, and its
      ability to migrate and form metastases.

PMID- 14704477
TI  - Nicotine diminishes anticonvulsant activity of antiepileptic drugs in mice.
AB  - Nicotine administered acutely at subconvulsive dose of 4 mg/kg, significantly
      decreased the protective activity of valproate, carbamazepine, diphenylhydantoin,
      phenobarbital, topiramate and lamotrigine against maximal electroshock-induced
      tonic convulsions in mice. The obtained data may suggest that interaction between
      nicotine and antiepileptic drugs should be carefully considered as a cause of the
      therapeutic failure in epileptic patients.

PMID- 14704478
TI  - Evaluation of interaction between gabapentin and baclofen in the formalin test in
      mice.
AB  - Gabapentin and baclofen at doses not affecting motor performance, produced dose
      dependent inhibition of both phases in the formalin test in mice. Isobolographic
      analysis revealed an additive interaction between the studied drugs in the second
      phase of the formalin test. Gabapentin given at doses effective in both phases of
      the formalin test significantly potentiated baclofen-induced motor impairment.

PMID- 14704479
TI  - Report on the German-Polish symposium "Thirty years of cooperation between German
      and Polish pharmacologists. New perspectives in the Common Europe", Bialowieza,
      September 18-21, 2003.

PMID- 14704480
TI  - MSRV pol sequence copy number as a potential marker of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a neurological disease in which demyelination in the
      brain and spinal cord is observed. The causal influence of bacterial/viral
      infections and genetic/immune factors in the etiology of multiple sclerosis is
      suggested. Multiple sclerosis-related retrovirus (MSRV) is one of the potential
      agents, which can lead to development of the disease. The aim of cytogenetic
      studies was assessment of MSRV pol sequence copy number in patients with MS
      compared to normal individuals. Cytogenetic slides with interphase nuclei and
      extended chromatin fibers were prepared from peripheral blood of 16 patients with
      MS and 10 healthy individuals. Fluorescence in situ hybridization (FISH) with
      biotinylated product of polymerase chain reaction was used in order to analyze
      MSRV pol sequence copy number in the examined material. Detection of MSRV pol
      probe was carried out by immunological reaction with avidin-fluorescein and
      biotinylated anti-avidin. MSRV pol sequence copy number was significantly greater
      in MS patients than in normal individuals. Using FISH technique to extended
      chromatin fibers, it was observed that MSRV pol exists as tandem repeats on
      various chromosomes. The increased number of MSRV pol sequence has been found on
      chromatin fibers of MS patients as compared to healthy controls.

PMID- 14704482
TI  - Different vulnerability to cytotoxicity and susceptibility to protection of
      progenitors versus mature oligodendrocytes.
AB  - Oligodendrocytes are known to be particularly vulnerable to the cytotoxic effect
      evoked by different neurodegenerative processes, such as ischemic insult,
      hypoxia, hypoglycemia or autoaggressive immunological attack like SM. They are
      the neural cells that undergo sophisticated process of maturation characterized
      by huge changes in cell metabolism and morphology. Small bipolar cells
      differentiate into multiprocessed mature oligodendrocytes capable of myelinating
      CNS. A question arises whether there are any differences in their sensitivity to
      excitotoxic events? To address this problem, the cells of two distinct stages of
      differentiation, i.e. progenitors (O-2A) and mature, myelinating oligodendrocytes
      (MBP+) were selected for investigation of the effects of such apoptogenic factors
      as H(2)O(2) or serum-withdrawal in vitro. Primary cultures obtained from the
      brain hemispheres of 18 days old Wistar rat embryos served after 10 days for the
      establishing pure oligodendrocyte culture (the "shake-off" method by McCarthy and
      de Vellis, 1980). Oligodendrocytes were cultured in DMEM with addition of
      insulin, transferrin and sodium selenite. Cytotoxic influence of selected
      apoptotic factors as well as neuroprotective effects of CsA were estimated by
      immunochemical detection. The obtained data suggest that progenitors and mature
      cells respond to apoptogenic conditions by activation of different molecular
      pathways and specific cytoprotective conditions should be worked out for each
      type of the cells.

PMID- 14704481
TI  - Effect of immunomodulatory treatment of multiple sclerosis on lymphocyte surface
      immunomarkers.
AB  - The aim of this study was to analyze the effect of immunomodulatory treatment of
      multiple sclerosis (MS) on lymphocyte surface immunomarkers. The special
      attention was given to TCR alpha/beta, gamma/delta and alpha/beta HLA-DR markers.
      Peripheral blood was obtained from 39 patients with clinically definite R-R MS,
      fulfilling the criteria of McDonald et al.[5]. The group of 15 patients was
      treated with interferon beta-1a (Avonex) intramuscularly once a week. The blood
      was obtained before and after two years of treatment. The other group of 10
      patients was treated every day with 20 mg of glatiramer acetate (Copaxone)
      intracutaneously. Subsets of lymphocytes were analyzed by the method of flow
      cytometry, using monoclonal antibodies produced by Ortho Diagnostic System. The
      relative results were evaluated using Immuno Count II program. The frequency of
      the studied subsets in MS was markedly different from that in healthy persons.
      The higher number of CD4, TCR alpha/beta positive cells and higher CD4/CD8 ratio
      was observed. In comparison to healthy individuals, in MS patients a decreased
      number of TCR gamma/delta, and alpha/beta HLA-DR was found. After therapy with
      glatiramer acetate, CD3 and CD8 positive lymphocytes were more frequently
      observed than before the drug administration. The CD4/CD8 ratio was markedly
      decreased. The effect of interferon beta-1a treatment was similar as in the
      previous group, i.e. a slight increase in CD3 and CD8 was noticed after therapy.
      Despite the differences in action of both immunomodulatory drugs, which was
      established in several studies, we like to stress some similarity in their effect
      on CD3, CD8, alpha/beta HLA-DR and gamma/delta HLA-DR immunomarkers frequency in
      lymphocyte, and on the CD4/CD8 ratio. This may mean that there are some common
      immunological steps of special importance for the clinical effect in MS.

PMID- 14704483
TI  - Non-genomic effect of estradiol on plasma membrane calcium pump activity in
      vitro.
AB  - The aim of the presented study was to compare the effect of 17-beta-estradiol on
      the hydrolytic activity of plasma membrane calcium pump (PMCA) purified from
      excitable (rat cortical synaptosomes) and non-excitable (human erythrocytes)
      cells. Both types of cell membranes contained different composition of the PMCA
      isoforms. To elucidate if the hormone action could depend on structure of PMCA
      protein, we assayed the hormone effect on Ca(2+)-ATP-ases pretreated for 15 and
      40 min with trypsin. The full length and trypsin-treated Ca(2+)-ATP-ases were
      next incubated with 17-beta-estradiol at a concentration of 10(-9) and 10(-7) M.
      In addition, stimulation of calcium pumps by naturally existing activator,
      calmodulin, was tested. The activity of synaptosomal and erythrocyte Ca(2+)-ATP
      ases was differently altered in the trypsin-treated samples. At physiologically
      relevant concentration of estradiol (10(-9) M), a significant enhancement of the
      activity was observed for synaptosomal Ca(2+)-ATP-ase, and a further increase
      occurred in the enzyme treated with trypsin for 15 min. The highest activity of
      erythrocyte calcium pump was induced after 40 min of incubation with protease.
      Moreover, the potency of the truncated calcium pump to promote ATP hydrolysis was
      approximately 2-fold elevated in the presence of 17-beta-estradiol. Calmodulin
      significantly stimulated the Ca(2+)-ATP-ase, but only the erythrocyte enzyme
      digested with trypsin for 15 min. It may be suggested that PMCA is a target for
      estradiol, that shows different mechanisms of action depending on isoform
      compositions and structural features of the enzyme.

PMID- 14704484
TI  - Dual action of cyclin-dependent kinase inhibitors: induction of cell cycle arrest
      and apoptosis. A comparison of the effects exerted by roscovitine and cisplatin.
AB  - Cyclin-dependent kinases (CDKs) have recently raised considerable interest in
      view of their key role in the regulation of the cell cycle progression. In
      proliferating cells, distinct CDKs associated with specific cyclins coordinate in
      an orchestrated way the appropriate transition between different phases of the
      cell cycle. Mutations and/or aberrant expression of distinct CDKs and their
      regulatory components lead to uncontrolled proliferation and finally to
      carcinogenesis. However, in post-mitotic neurons, all CDKs with the exception of
      CDK5 are silent. CDK5, a proline-directed serine/threonine kinase exhibiting a
      close structural homology to the mitotic CDKs, binds to p35, the neuron-specific
      regulatory subunit of CDK5. CDK5 is very abundant in mature neurons and seems to
      regulate neurotransmitter release through phosphorylation and down-regulation of
      calcium channel activity. Therefore, the inhibition of CDKs in neurons after
      oxidative stress and in neurodegenerative disorders has a protective action.
      Selective CDKs inhibitors were developed as promising drugs for cancer therapy
      due to their ability to arrest cell cycle progression. The aim of this study was
      to compare the anti-proliferative effect of roscovitine (ROSC), a potent CDKs
      inhibitor, with that of cisplatin (CP) on human breast cancer MCF-7 cells. ROSC
      exerted stronger inhibitory effect on proliferation and cell cycle progression of
      MCF-7 than CP. Accumulation of G(2)/M arrested cells starting 6 h after onset of
      ROSC treatment coincided with a strong up-regulation of the p53. Reconstitution
      with caspase-3 sensitized MCF-7 cells to CP action. It implicates that ROSC
      inhibits more selectively and efficaciously the proliferation of human breast
      carcinoma cells.

PMID- 14704485
TI  - Cannabinoids alter recognition memory in rats.
AB  - Cannabinoids are known to attenuate learning and memory in both humans and
      animals. In rodents, disruptive effect of cannabinoids on memory, reversed by SR
      141716, a specific CB(1) receptor antagonist, was shown in behavioral tests based
      on conditioning. There are no data concerning the influence of cannabinoids on
      recognition memory. Recently, the improvement of recognition memory in
      cannabinoid CB(1) receptor knock-out mice was reported. Therefore, the purpose of
      the present study was to determine whether a stable analogue of endogenous
      cannabinoid anandamide, R-(+)-methanandamide (0.25 and 2.5 mg/kg, i.p.) and a
      potent CB(1) receptor agonist, CP 55,940 (0.025 and 0.25 mg/kg i.p.) affect
      recognition memory in rats evaluated in an object recognition test, based on
      discrimination between the familiar and a new object presented at 1h interval.
      Because cannabinoids at the higher doses can produce motor inhibition, the
      influence of both compounds on psychomotor activity was evaluated in an open
      field test. CP 55,940 and R-(+)-methanandamide, at both doses given once, 15 min
      before the learning trial, significantly attenuated recognition memory, measured
      by the difference in exploration of a new object and a duplicate of the familiar
      object. Moreover, CP 55,940 at the higher dose significantly attenuated
      ambulation, and bar approaches, and at both doses also rearings, evaluated in an
      open field, performed immediately after an object recognition test, while R-(+)
      methanandamide at both doses did not alter locomotor and exploratory activity of
      rats. This is the first evidence that cannabinoids impair recognition memory in
      rats.

PMID- 14704486
TI  - Apolipoprotein E4 and A beta peptide 1-42 inhibit polyphosphoinositide
      biosynthesis in rat brain cortex.
AB  - Polyphosphoinositides synthesized by phosphatidylinositol 4-kinase, EC 2.7.1.67
      (PI4K) and phosphatidylinositol 4-phosphate 5-kinase, EC 2.7.1.68 (PIP5K) are
      involved in cell signaling and cytoskeleton function. In this study, the effect
      of apolipoprotein E4 (apoE4) and amyloid beta peptide A beta 1-42 on PI4K and
      PIP5K activity in cortical synaptic plasma membranes from rat brain was
      investigated. The results indicated that 0.25 microM apoE4 inhibited PI4K and
      PIP5K by 40% and 30%, respectively, but 25 microM A beta 1-42 decreased
      exclusively PI4K activity by 20%. Although the mechanism of apoE4 and A beta
      action is unknown and needs future investigation, this study suggests that free
      radical-dependent protein oxidation may be involved in alteration of these
      enzymes.

PMID- 14704488
TI  - [Qualitative research in evaluation of health promotion programs in the context
      of health and disease paradigms].
AB  - The authors analyse selected aspects of evaluation research in relation to the
      changing paradigms of health and disease. The process of change in the biomedical
      paradigm, gradually becoming the biopsychosocial (socioecological), holistic
      model, is discussed. A short description of the two paradigms is given, including
      a critique of the biomedical model of health and disease based on evidence from
      social science research. In particular the wide definition of evaluation and the
      effectiveness of evaluation studies in health promotion are discussed. Selected
      practical consequences of accepting the democratic role of evaluation are
      analysed. The significance of the formative aspects of evaluative procedures for
      creating, modifying and implementing health promotion programmes is discussed.
      Another issue included in this analysis is the problem of objectivity of
      evaluation studies and the status of the evaluator in relation to other persons
      involved in programme implementation. The effectiveness of evaluation studies in
      relation to the biomedical and biopsychosocial paradigms are discussed in the
      context of differences between quantitative and qualitative evaluation methods.
      More detailed discussion concerns qualitative evaluation using selected methods,
      in particular participatory observation and, to a lesser degree, individual and
      group interviews. The reasons for the relatively low popularity of qualitative
      evaluation studies in health promotion programmes, especially in the field, are
      analysed. Moreover, the relation between health promotion and prevention (the so
      called problem prevention) in relation to the biopsychosocial paradigm is
      analysed; also a short reference is made to the issue of the changing status of
      the patient (from "object" to " subject" ) in contacts with medical institutions,
      in context of the changing image of health and disease.

PMID- 14704487
TI  - Transition metal ions significantly decrease phospholipase C activity degrading
      phosphatidylinositol-4,5-bisphosphate in the brain cortex.
AB  - Highly reactive transition metals, such as copper and iron play an obligatory
      role in generating of reactive oxygen species (ROS). Many neurodegenerative
      diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) show
      increased accumulation of these metals. Phosphoinositide metabolism is altered in
      neurodegenerative diseases. In the present study, we examined the effect of
      CuSO(4) and FeCl(2) on phospholipase C (PLC) activity degrading
      phosphatidylinositol-4,5-bisphosphate (PIP(2)) and phosphatidylinositol (PI) in
      synaptic plasma membranes (SPM) from the rat brain cortex. We report that 25
      microM CuSO(4) and FeCl(2) decreased PIP(2)-PLC activity by 60% and 75%,
      respectively. However, both compounds had no effect on PI-PLC activity. These
      data indicated that exclusively PIP(2)-PLC is sensitive to transition metal ions.
      We suggest that chelators of these metals may protect brain against alteration of
      phosphoinositide metabolism and might be beneficial in the treatment of
      neurodegenerative diseases.

PMID- 14704489
TI  - [Health-related quality of life (HRQL) in children and adolescents--concepts,
      study methods and selected applications].
AB  - The importance of subjective health measures has increased over the recent years.
      Prevention of acute and chronic diseases and early intervention in children
      depend upon availability of measures that can be routinely used for monitoring
      purposes. Traditional outcome measures (survival, laboratory tests) have limited
      value when assessing health status of chronically ill persons or screening
      population. Research on quality of life has a solid methodological background.
      High importance is attached to psychometric characteristics of developed
      questionnaires. However, only a few (especially generic) instruments have been
      developed for children and youth. The aim of the study is: 1) to describe the
      main concepts and methods in quality of life research in relation to paediatric
      practice; 2) to present the KIDSCREEN project sponsored by European Commission,
      currently in progress. The KIDSCREEN multicenter project is being developed by 13
      European countries, including Poland, within the 5th Framework Programme Quality
      of Life and Management of Living Resources. The project will provide the
      opportunity to measure the HRQL in children and adolescents across different
      countries and cultures using a standardized multidimensional instrument developed
      at the same time in all participating countries. It is expected that it will
      improve medical, psychological and educational care of children and adolescents
      and will be very useful in changing the system of preventive health care provided
      in Polish schools. Applying the KIDSCREEN questionnaire in selected EU candidate
      countries will anticipate the problems that could affect other countries in the
      same economic situation.

PMID- 14704490
TI  - [Some problems in the cross-cultural adaptation of programs for primary
      prevention of alcohol abuse].
AB  - The subject of this article is a presentation of chosen problems connected with
      cross-cultural adaptation of school-based prevention programmes. These problems
      are described according to an example of the two first parts of the American
      Northland Project. The aim of this project is to delay the onset of alcohol use
      among young adolescents. As the first step, the adaptation required an expert
      opinion on the goals and theoretical background of the Northland Project. The
      second was adjustment of the programme to Polish cultural conditions - however,
      these changes could not modify the prevention strategies, which were used in the
      programme and which determined its effectiveness. The goal of the adaptation was
      creation of the Polish version, which will be accepted by students, their parents
      and teachers. The final step of adaptation, was evaluation of the effectiveness
      of the Polish version of the programme.

PMID- 14704491
TI  - [Parents and children in families with alcohol problems--anthropologic and
      preventive study].
AB  - The paper describes the proposition of solution of a difficult dilemma concerning
      the real role of parents in the development of children in families with alcohol
      problem (alcohol misuse and dependency of parents). From one side drinking
      parents are the cause of serious destruction of child health and development.
      From the other side we have the data about positive influence of strong bonds
      between children and their parents in alcohol use prevention (parenting as
      protective factor). Original philosophical theory of person structure with
      additional theory of parenting supplies the possibility of the solution of the
      dilemma. It is necessary to differentiate the personal relationship and the
      emotions (and behaviours) as two different levels of bonding. Alcohol dependent
      parents have influence on both levels, they protect and make the risk at the same
      time. The proposal is that the protective influence is still more powerful and
      important, so it is necessary to protect bonds between children and their parents
      despite the fact of some lateral destruction. It is also necessary to confront
      parents with the effects of their behaviour (intervention, therapy) to develop
      their possibilities to renovate their parenting functions, which is necessary for
      effective prevention. The theory allows to understand the situation of the child
      in the alcohol family more precisely. It is especially important for social
      workers, teachers and therapists working with such families. Some rules for
      working with the children of alcoholics are formulated.

PMID- 14704492
TI  - [Alcohol drinking and other risk behaviors among adolescents aged 11-15 years].
AB  - The aim of the study was: (1) to assess the prevalence and intensity of alcohol
      drinking among 11 to 15-year-old Polish adolescents in 2002, (2) to show trends
      of drinking between 1998-2002, (3) to identify three groups of alcohol-related
      risk (low, moderate and high intensity of drinking); (4) to test the relationship
      between belonging to those groups and other health compromising behaviours. The
      study is based on the fourth series of - Health Behaviour in School-Aged Children
      (HBSC) A WHO Collaborative Cross-National Study carried out in 2002. A sample was
      selected as representative of general school population at three age groups -
      mean age 11.7; 13.7 and 15.7 (N=6383). An international standard questionnaire
      was used. The results showed that 29% of students, including 51% of 15-years
      olds, had been really drunk at least once in the lifetime. 11% of all
      adolescents, including 21% of 15-year-olds, were identified as the high risk
      group. In 1998-2002 an increase of adolescents drinking vodka and of girls being
      drunk was observed. The girls living in towns formed the main group of
      adolescents with increasing alcohol consumption. In multivariate logistic
      regression models adjusted, if appropriate, for gender, place of residence and
      age, being in the group of high alcohol-related risk was associated with higher
      risk of smoking (odds ratio OR=23.3; 95% confidence interval CI=18.3-30.3),
      illicit drugs use (for marihuana or hashish OR=49.0; 95% CI=21.3-112.7), early
      sexual initiation (OR=9.9; 95% CI=7.1-14.1), participation in a physical fight or
      bullying (OR=5.1; 95% CI=4.2-6.3), and getting injured (OR=1.9; 95% CI=1.6-2.3).
      Being in the group of moderate alcohol-related risk was also associated with
      other risk behaviours, with lower, but still significant odds ratios. Presented
      data can be used in school-based and community-based prevention and intervention
      activities.

PMID- 14704493
TI  - [Adolescents' free time activities and substance use].
AB  - The aim of this study was to test the strength of the relationship between
      adolescents' free time activities and substance use, against a background of
      other factors important for substance use. A survey of 1843 students in grades:
      seven, nine and ten in Ilawa (84% of target population) was conducted in December
      2001. The results of stepwise logistic regression (with Wald statistics) showed
      that some forms of adolescents' free time activities are directly significant for
      substance use, others - are not, when controlling for factors, such as: previous
      usage of other substances, participation in company of peers using illegal drugs
      or drinking alcohol, academic achievement, religious involvement and parental
      alcohol drinking or cigarette smoking. Frequent, individual sport activity was
      found to be associated with less substance use: non-smoking and non-drinking.
      Participation in various organised activities (without sport) was significant
      only for cigarette non-smoking. None of the adolescents' free time activities
      were significant predictors concerning illegal drug use.

PMID- 14704494
TI  - [Trends in cigarette smoking among Warsaw teenagers: the Mokotow study 1984
      2000].
AB  - Since mid 1980s self-report anonymous surveys were repeated in all types of
      secondary schools in Mokotow - the biggest district of Warsaw. The study was
      aimed at trends and patterns in teenagers' substance use including cigarette
      smoking. Between 1984-2000 there were five surveys utilizing the same procedure
      and instruments and targeted at 15 years old students. The number of students
      participating in these five surveys ranged from 2000 to 3900. RESULTS: Between
      1988-2000 total cigarette use had increased from about 26% to 36%. This increase
      was mainly influenced by the shift in daily smoking rates - from about 10% in
      1988 to nearly 18% in 2000. These changes were stronger among girls. In this
      period the rates of female daily smoking had increased nearly three times and
      reached about 18% in 2000. As a result in 2000 smoking rates became similar
      (daily smoking) or were even higher among girls if total smoking was considered.
      Systematic growth in cigarette use among girls observed since 1988 reflects
      general changes in health-related behaviour of teen-age girls. Growing smoking
      rates among 15 year old students were in contrast with decreasing tendencies
      observed among their parents. Between 1984 and 2000 the group of students having
      both nonsmoking parents increased about 10%. Results of multivariable logistic
      regression confirmed that alcohol use and company of drug taking peers are the
      most prominent risk factors for smoking among the 15 year olds. Other significant
      risk factors were connected with school career (poor academic achievement and
      type of secondary school) and family patterns (regularly smoking parents). The
      relationship between these factors and teenager smoking was stable during the
      years covered by the Mokotow study. CONCLUSIONS: Cigarette smoking among Warsaw
      teenagers increased significantly in the past decade, which consistent with the
      general increase in psychoactive substance use among youth in Poland. This
      process can be considered as a real challenge for teachers and physicians working
      with youth.

PMID- 14704495
TI  - [Bullies and victims among Polish school-aged children].
AB  - The objective of the study was to determine the prevalence of bullying in Polish
      schools and to evaluate the relationship between bullying and substances abuse.
      Data obtained through HBSC (Health Behaviour in School-Aged Children. A WHO Cross
      National Study) conducted in Poland in 2002 were used. The representative sample
      comprised 6383 students 11, 13 and 15 years of age. The indicators of total and
      frequent bullying were defined and five main ways of bullying were described.
      Relationship between bullying and substance abuse was evaluated by logistic
      regression models adjusted for age and gender with frequent (at least 2-3 times a
      month) bullying as dependent variable. Results showed that 20% of students were
      involved in frequent bullying; 10% as perpetrator, 8% as victim and 2% as both.
      More boys than girls reported being involved in bullying both as victims and
      perpetrators. The prevalence of victimization decreased with age while the
      prevalence of bullying increased. Verbal bullying was the main way of bullying
      reported by students. 10% of students suffered from physical violence and 16%
      reported bullying others in physical ways. The difference between boys and girls
      was higher for physical bullying. Frequent episodes of drunkenness (more than 10
      times in the lifetime) increased the risk of bullying about 7 times (OR=6.8;
      CI=4.9-9.4). Every day tobacco smoking and frequent marihuana use resulted in
      three fold increase in the risk of bullying. The positive results of the
      Norwegian anti-bullying programme provided by D. Olweus as well as other examples
      of anti-bullying strategies developed recently within the European Community and
      model approaches from Australia are described.

PMID- 14704496
TI  - [Use and abuse of alcohol and other psychoactive substances among Polish
      university students].
AB  - The results of country-wide research on alcohol and psychoactive substances use
      among Polish students are presented. The survey was carried out in the year 2000
      and included 9446 students from 8 major academic centres in Poland. Negative
      events linked with the use of alcohol and drugs were discovered - 40% of students
      (42% of men and 37% of women) during the last two weeks exceeded the limit of
      dangerous drinking. Large range of harmful consequences of binge drinking has
      been found - one in three men and one in four women committed acts under the
      influence of alcohol, which they regretted after. One in four men under influence
      of alcohol was involved in aggressive fights with peers and one in six has had
      serious trouble with studying and bad assessments. The scope of drug use was much
      smaller but also alarming. During the last 30 days 7% of the studied population
      reported use of marijuana and 1.5% amphetamine. Abuse of alcohol was correlated
      with use of drugs. This creates a serious risk of cross addiction and shows an
      important role of alcohol drinking as a gateway to drug use.

PMID- 14704497
TI  - [Evaluation of a school-based intervention method for drug using students].
AB  - The article presents the study results concerning the feasibility of an
      intervention method for drug using students in the school environment. The
      representatives of 11 schools from three towns took part in focus group
      interviews. They shared their experiences related to the use of this method in
      practice. During the research period 34 interventions were conducted. Most of
      them were held according to the basic assumptions of the intervention method. In
      the opinion of the respondents, 15 of the undertaken interventions finished
      successfully. This means, that persistent change in student behaviour was
      achieved or there was no evidence of further breaking school rules by the
      student. The outcome of the study indicates, that the probability of achieving
      desired effects was going up with the increase in the number of implemented
      components of the intervention method. The gathered information allows to
      conclude that this school-based intervention method can be useful for the school
      staff and that for most part, it fits their potential skills.

PMID- 14704498
TI  - [Introduction of a school-based intervention method targeted for drug using
      students. Barriers related to the co-operation between parents and teachers].
AB  - The aim of the study was to analyse the process of implementing a school-based
      intervention method, for drug using students and barriers, related to the parent
      school co-operation, impeding this process. Data were collected during the
      qualitative evaluation of the intervention implementation into 11 schools
      representing various educational levels and local communities. Results indicate
      that in 6 schools at least some of proposed system modifications were implemented
      and in 7 schools teachers used key elements of the intervention method while
      solving problems related to students' conduct or drug use. The teachers' attitude
      and expectations related to the idea of family-school co-operation were important
      from the very beginning of the programme implementation - at the stage of
      establishing a sense of urgency of the change. In proceeding stages, good
      communication and openness in parent-school contacts were crucial for the
      programme effectiveness. These were also a source of positive reinforcement for
      the people involved.

PMID- 14704499
TI  - [Preventive health care for students--the principles and implementation].
AB  - The aim of this article is the presentation of principles in reforming preventive
      health care system for pupils. In this context the goals and tasks of school
      health care policy programme "Implementation of standards in health care for
      school-age population" are shown and discussed. Results of programme realisation
      in 2002 are also discussed.

PMID- 14704500
TI  - [Standards of preventive health care for students].
AB  - The goal of this work is the presentation of the first version of standards in
      preventive health care over pupils in Poland, carried out by school nurses or
      school hygienists and primary health care physicians. Targets, main principles of
      standards and the course of all activities during their preparation are
      discussed. Main elements of this document: standards of requirements concerning
      qualifications, employment of personnel performing preventive health care over
      pupils, prophylactic room in school, equipment and procedures in preventive
      health care of pupils are presented. Standards of procedures and indicators of
      their implementation are also discussed.

PMID- 14704501
TI  - Photodynamic therapy: mechanism of action and ways to improve the efficiency of
      treatment.
AB  - Photodynamic therapy is treatment modality involving the administration of
      photosensitizing compound, which selectively accumulates in the
      hyperproliferative target cells followed by local irradiation with visible light
      of lesion. Eventually target tissue will be damaged by necrosis and apoptosis.
      Action of treatment is described from absorption of light till damage of tissue.
      Several rationale proposals to increase the efficiency of described treatment
      modality are suggested: to evaluate the antiproliferative activity of new coming
      photosensitizers, to combine photosensitization with other treatment modalities
      in molecular level, exploring mechanism of apoptosis, to increase the efficiency
      of treatment by combination with ionizing radiation, hyperthermia or ligation of
      peripheral benzodiazepine receptors.

PMID- 14704502
TI  - [Oxidative stress and endothelial dysfunction].
AB  - Growing numbers of morbidity and mortality due to the Coronary Heart Disease
      (CHD) is recognized as the more increasing challenge in the world. The initial
      stage of atherosclerosis, early diagnosis and treatment of CHD are the main
      objectives of current research. Endothelium dysfunction, the earliest expression
      of the atherosclerotic process is associated with subtle biochemical changes that
      gradually are transformed into the structural changes of the arterial wall. The
      theory of free radicals is the most common among the atherosclerosis
      explanations. Overproduction or impaired neutralization of the free radicals
      accounts for oxidative stress that is causing substantial damage to the low
      density lipoproteins, nitric oxyde (NO), endothelium cells, tissue cells and
      finally leads to the endothelium dysfuction. Pathophysiology of oxidative stress
      and its role in the endothelium dysfunction are discussed in this paper. Positive
      role of various medications (statins, angiotensin converting enzym inhibitors,
      aldosteron antagonists, estrogens, antioxidants, b-blockers with vasodilatative
      properties) to the oxidative stress and consequently to the endothelium
      dysfuction are discussed as well.

PMID- 14704503
TI  - [Low density lipoprotein apheresis].
AB  - Increased blood cholesterol concentration is one of the main factors in ischemic
      heart disease, development of which is determined by atherosclerotic changes in
      coronary vessels. Diet and treatment with 3-hydroxi-3-metilglutaril coenzyme A
      (HMG-CoA) reductase inhibitors helps to reduce low density lipoprotein
      cholesterol (LDL-Ch) blood concentration up to recommended level of 3.0 mmol/l in
      most patients but in some patients particularly with familial dyslipidemias
      cholesterol concentration remains increased even after treatment with maximal
      doses of lipid-regulating agents or their combinations. The most frequently used
      mechanical methods of cholesterol removal from blood include the procedures of
      extracorporeal apheresis. Low density lipoprotein (LDL) apheresis not only
      significantly reduces the blood concentrations of total cholesterol (TCh), and
      LDL-Ch, lipoprotein (a) (Lp(a) and fibrinogen but also stops the progression of
      atherosclerosis in coronary vessels.

PMID- 14704504
TI  - [Role of tissue factor in atherothrombosis].
AB  - Tissue factor is a key enzyme in coagulation process. It is primary known as a
      cofactor for factor VIIa-mediated triggering of blood coagulation, which proceeds
      in a cascade of extracellular reactions. Tissue factor forms a catalytic complex
      with VIIa and intitiates coagulation by activating factor IX and X, ultimately
      resulting in thrombin formation. Being a transmembranic glycoprotein it takes a
      signalling information to another cell activity after endothelium or other tissue
      damage. Tissue factor plays a pivotal role in blood clotting physiology and
      pathology especialy in atherothrombosis. Thrombogenic tissue factor on cell
      derived microparticles is present in the circulating blood of patients with acute
      coronary syndromes. Tissue factor is found in adventitia of blood vessels and the
      lipid core of atherosclerotic plaques (but not in vascular cells contacting
      directly with blood). Although the molecular mechanisms responsible for these
      phenomena remain unclear, it is thought that they are brought about by the action
      of intracellular signaling, resulting in gene transcription and subsequent
      protein synthesis. By expressing on monocyte or macrofage cell membrane surface
      it is involved in proinflammatory action and plaque destabilisation. This shifted
      the emphasis to investigations of what happened on the cell surface, and later to
      the cell biology of tissue factor and its inducibility in monocytes/macrophages
      and endothelial cells. Recent studies have suggested that tissue factor also
      plays non-hemostatic roles in blood vessel development, tumor angiogenesis and
      metastasis, inflamation. Tissue factor upregulates a number of genes involved in
      regulation of growth, transcription, and cellular motility, as well as cytokines,
      makes it possible to suggest a link between the formation of the tissue factor /
      VIIa complex and the cellular processes. Regulation of tissue factor activity by
      natural tissue factor pathway inhibitor (synthesized by vascular endothelial
      cells) or by special drugs is a new insight in thrombosis and vessel reocclusion
      preventive therapy. Tissue factor concentration in circulating blood has a higher
      informativity comparing to troponine and CRB values.

PMID- 14704505
TI  - Factor V Leiden and post thromboembolic pulmonary hypertension.
AB  - Literature review and original data concerning the most common cause of inherited
      thrombophilia - activated protein C resistance have been presented. One hundred
      and three patients with confirmed venous thromboembolism have been investigated
      for activated protein C resistance with 2 ( nd ) generation "Diagnostica Stago"
      test. Activated protein C resistance has been found in 22.3 % cases. In the group
      of 70 healthy unselected men and women, matched by sex and age, this mutation has
      been found in 7.1% cases. Out of 101 patients with pulmonary thromboembolism
      confirmed by pulmoangiography or perfusion lung scan, 78 have been investigated
      by Doppler echocardioscopy in order to detect pulmonary hypertension after 1.5
      months. Statistically significant correlation between age and pulmonary artery
      pressure has been found. No correlation between pulmonary artery pressure and
      activated protein C resistance has been detected.

PMID- 14704507
TI  - From classical epidemiological research to health policy formulation:
      contribution of Kaunas-Rotterdam Intervention Study.
AB  - The aim of the article is to review the contribution of WHO coordinated Kaunas
      Rotterdam Intervention Study (KRIS) to the development of epidemiological
      research in cardiovascular and other noncommunicable diseases at Kaunas
      University of Medicine and in Lithuania at large. KRIS impact on broadening
      international collaboration with and through WHO at Kaunas University of Medicine
      and Lithuania at large is presented. KRIS contribution to the development of
      scientific basis for cardiovascular risk assessment as well as backing-up the
      concept of integrated prevention of noncommunicable diseases is highlighted. Its
      role as a bridging agent between research, education and public health
      development in Lithuania as well as internationally is being discussed. The road
      that KRIS experience based team underwent from executors of classical
      epidemiological studies to generation of new concepts in noncommunicable disease
      prevention as well as contribution to national health policy formulation is
      presented.

PMID- 14704506
TI  - [Correction of corneal astigmatism during phacoemulsification].
AB  - OBJECTIVE: To evaluate the effectiveness of clear corneal incisions and opposite
      clear corneal incisions for correcting corneal astigmatism during
      phacoemulsification. METHODS: Twenty-nine patients (37 eyes) underwent
      phacoemulsification with foldable intraocular lens implantation through a 4.0 mm
      clear corneal tunnel. In the group 1 (28 eyes) the corneal tunnel incisions were
      placed on the steepest axis (pre-operative astigmatism >/ =1.5). In the group 2
      (9 eyes) an additional penetrating incision (3.0 mm) was placed on the opposite
      side to enhance flattening effect (pre-operative astigmatism =1.5). Keratometry
      was done in all eyes on the day prior to surgery and on the first day, 2-3 weeks
      and 6 months post-operatively. RESULTS. After 6 months, the corneal astigmatism
      decreased from 0.96 D+/-0.03 to 0.78 D+/-0.06, p</=0.05 in the first group and
      from 2.23 D+/-0.21 to 1.56 D+/-0.18, p< or = p</0.05 in the second group.
      CONCLUSIONS: Clear corneal incision on the steepest axis has neutralizing effect
      on pre-operative astigmatism. Adding opposite clear corneal incisions can greatly
      enhance this flattening effect [corrected].

PMID- 14704508
TI  - Trends in main cardiovascular risk factors among middle-aged Kaunas population
      between 1983 and 2002.
AB  - OBJECTIVE OF THE STUDY: To evaluate dynamics in prevalence of main risk factors
      of cardiovascular diseases among middle-aged Kaunas population between 1993 and
      2002. MATERIAL AND METHODS: Four independent surveys in 1983-1984, 1986-1987,
      1992-1993, and 2001-2002 were carried out in random samples of men and women aged
      35-64 involving 2413, 1762, 1231 and 1403 persons respectively. The risk factors
      were defined within the framework of the WHO MONICA study (Multinational
      Monitoring of Trends and Determinants in Cardiovascular Disease). RESULTS: During
      the 19 years the mean values of systolic blood pressure decreased among men.
      Among women decreased both mean values of systolic and diastolic blood pressure,
      however the prevalence of hypertension has decreased only among women by 11.9%,
      with no significant changes among men. The prevalence of overweight decreased
      among men, and the prevalence of obesity declined among women. Among women the
      body mass index decreased as well. No changes in the prevalence of
      hypercholesterolemia among men (80.7%) as well as among women (82.7%) have been
      detected, meanwhile the mean of total cholesterol among men increased from 5.9
      mmol/l to 6.1 mmol/l and among women - from 6.09 mmol/l to 6.31 mmol/l (p<0.001).
      The prevalence of smoking has increased by 7.2% among women and didn't change
      among men. IN CONCLUSION: The decreasing trends in the prevalence of some risk
      factors have been estimated in Kaunas middle-aged population during 1983-2002
      years. However the profile of cardiovascular disease risk factors is still rather
      high. Programs or strategies targeted to control levels of main cardiovascular
      disease risk factors are urgently needed.

PMID- 14704509
TI  - Overweight and increased blood pressure in preschool-aged children.
AB  - This paper presents the data on height, weight, body mass index, systolic and
      diastolic blood pressure of 3-7 year old children. A sample of preschoolers
      (n=1441) was drawn from the kindergartens in Kaunas city (Lithuania). The 5 ( th
      ), 10 ( th ), 50 ( th ), 90 ( th ) and 95 ( th ) percentiles were estimated for
      studied variables and the criteria for the overweight and increased blood
      pressure were calculated. It was shown that body mass index could be used as an
      indicator of the child's physical development. Its value 14-18 kg/m ( 2 )
      indicates an optimal child's growing, value < or = 14 kg/m ( 2 ) - the
      underweight, value > or =18 kg/m ( 2 ) - the overweight. According to these
      criteria it was found that 7.4% of 3-7 year old children were underweight, 5.8%
      overweight. Increased blood pressure (over 90 ( th ) percentile of systolic
      or/and diastolic blood pressure) had 21.4% of examined children. The prevalence
      of increased blood pressure was significantly higher in obese than in normal
      weight children. We conclude that the significant prevalence of childhood
      overweight and increased blood pressure emerge in preschool aged children. Thus,
      we recommend investigations of prevention and intervention programs to be used in
      the preschool setting.

PMID- 14704510
TI  - Morbidity and mortality from the major cardiovascular diseases in Kaunas
      population from 1983 to 2002.
AB  - THE AIM of the present study was to evaluate the trends in morbidity and
      mortality from ischemic heart disease and stroke in Kaunas population aged 25-64
      years from 1983 to 2002. MATERIAL AND METHODS: The source of data is the official
      mortality statistics and Kaunas population-based ischemic heart disease and
      stroke registers. The methods used for the data collection were those applied by
      the WHO MONICA project. The object - all permanent residents of Kaunas aged 25-64
      years who died from ischemic heart disease and stroke in 1983-2002 and
      experienced ischemic heart disease or stroke in 1983-2000. The age-standardized
      rates were calculated by the direct method and using the Segi's World and
      European population as a standard. Trends were analyzed using the method of
      linear regression on logarithms of the age-standardized annual rates. RESULTS:
      During 1983 to 2000, the morbidity from acute myocardial infarction among Kaunas
      men aged 25-64 years decreased by 0.8%/yr. (p=0.08), and during 1986-2000, the
      morbidity from stroke among men of the same age was without significant changes (
      0.4%/yr., p=0.5). Among women, both the morbidity from acute myocardial
      infarction (1.6%/yr., p=0.006) and the morbidity from stroke (2.9%/yr.,
      p=0.000002) rates among women increased statistically significantly. During 1983
      to 2002, the mortality rates from acute myocardial infarction and stroke
      decreased statistically significantly among both men and women: among men - by
      2.2%/yr., p=0.003, and by 2.9%/yr., p=0.004, respectively; among women - by
      2.6%/yr., p=0.005, and by 3.2%/yr., p=0.002, respectively. CONCLUSIONS: The
      morbidity of acute myocardial infarction and stroke remained without significant
      changes among Kaunas men aged 25-64 years, while it increased statistically
      significantly among women of the same age during the last two decades. Among both
      men and women the mortality rates from both ischemic heart disease and stroke
      decreased significantly from 1983 to 2002.

PMID- 14704511
TI  - Prevalence of dyslipidemias among Lithuanian rural population (CINDI program).
AB  - The aim of this study is to describe trends in serum total, low and high density
      lipoprotein cholesterol, triglycerides and nutrition habits in Lithuanian rural
      population between 1987 and 1999. The article presents the data of three
      screenings of random samples of the population aged 25-64 of five Lithuanian
      rural regions. Since 1987 the prevalence of hypercholesterolemia has decreased.
      The greatest decrease was observed in the proportion of persons with elevated
      level of low-density lipoprotein cholesterol. The prevalence of low level of high
      density lipoprotein cholesterol decreased more significantly among women compared
      to men. The most remarkable changes in the prevalence of dyslipidemias were
      observed between 1993 and 1999. The increasing age was strongly correlated with
      higher prevalence of hypercholesterolemia in both genders. The prevalence of
      hypercholesterolemia was higher among men with higher education, overweight,
      hypertension and smokers than among those with low education, normal weight,
      normal level of blood pressure and nonsmokers. In women hypercholesterolemia was
      associated only with hypertension. The nutrition habits of Lithuanian rural
      population have changed, especially over the last five years. The consumption of
      animal fat has decreased and the usage of vegetable oil and margarine has
      increased. Women increased consumption of vegetables and fruits. The
      strengthening of favorable trends in nutrition habits in Lithuanian population
      should be one of the most important strategies in the implementation of
      cardiovascular disease prevention programs.

PMID- 14704512
TI  - The prevalence of overweight and obesity in relation to social and behavioral
      factors (Lithuanian health behavior monitoring).
AB  - The aim of the study is to estimate the trends in the prevalence of overweight
      and obesity among Lithuanian adult population and to examine the association of
      social and health behavior factors with overweight and obesity. Since 1994 five
      cross-sectional surveys have been conducted among adult population aged 20-64
      within the international FINBALT HEALTH MONITOR project. An independent national
      random sample of 3000 inhabitants of Lithuania was drawn from National Population
      Register for each survey. The data were collected through mailed questionnaires
      (covering sociodemographic characteristics, health behaviors, and self-reported
      height and weight). Overweight was defined as BMI>25 kg/m ( 2 ) and obesity - as
      BMI>30 kg/m ( 2 ). In 2002 the overall prevalence of obesity was 16% and the
      prevalence of overweight - 49.1%. Since 1994 both indicators have increased in
      men while in women the prevalence of overweight has decreased. The prevalence of
      obesity and overweight increased with age. Obesity and overweight were least
      prevalent among the highly educated women, but most prevalent among the highly
      educated men. Women living in cities were less obese and overweight than those
      living in towns and villages. Obesity and overweight were less prevalent among
      daily smokers and physically active persons. Women drinking beer at least once a
      week were less obese and overweight than those who consumed beer more rarely.
      There was no consistent association between nutrition habits and the prevalence
      of obesity and overweight. The National obesity control program aimed at
      promotion of healthy nutrition and physical activity should be elaborated in
      order to decrease the prevalence of obesity and overweight in Lithuanian
      population.

PMID- 14704513
TI  - Age-related maculopathy and consumption of fresh vegetables and fruits in urban
      elderly.
AB  - The purpose of this study was to investigate the rate of age-related maculopathy
      among elderly males and females in relation to frequency of consumption of fresh
      vegetables and fruit. During ophthalmological investigation of Kaunas city
      inhabitants aged 65-74 years (240 males and 206 females) age-related maculopathy
      (early and late) was determined for 22.1% of males and 20.4% of females.
      Frequency of usage of fresh (uncooked) vegetables and fruits in winter-spring and
      in summer-autumn seasons by investigated persons was determined, using food
      frequency questionnaire. In this work an association between age-related
      maculopathy and usage of vegetables and fruits has been investigated in 170 males
      and 181 females aged 65-74 years without diabetes who never smoked; age-related
      maculopathy was found for 18.8% of males and 17.7% of females. Obtained data have
      demonstrated an inverse association between consumption of vegetables during
      winter-spring season and age-related maculopathy: usage of vegetables two times a
      week or more versus usage less than two times a week decreases prevalence of age
      related maculopathy 2.0 times among males (OR=0.42; 95% CI 0.18-1.0; p=0.05) and
      2.2 times among females (OR=0.37; 95% CI 0.15-0.9; p=0.02). Data have
      demonstrated a tendency that increasing consumption of fresh vegetables and
      fruits during both seasons can reduce risk of age-related maculopathy among
      females. In conclusion, characteristic for Lithuanian urban elderly rare usage of
      fresh vegetables during winter-spring season can increase risk of age-related
      maculopathy independently from other risk factors.

PMID- 14704514
TI  - [Prevalence and risk factors of age-related maculopathy among middle aged
      people].
AB  - OBJECTIVE: To investigate the prevalence of age-related maculopathy and the
      relationships of age-related maculopathy to age, sex, ocular factors, education,
      work exposures. A population-based cohort study included 1357 subjects (35-64
      years of age) living in Kaunas (Lithuania), who were examined during the interval
      from 2001 to 2002. The diagnosis of age-related maculopathy was based on
      ophthalmoscopic findings or on fundus photographs. The prevalence of early age
      related maculopathy was 7.3% in persons 40-64 years of age. No late age-related
      maculopathy (AMD) was found. Prevalence of early age-related maculopathy was
      strongly related to age (P<0.001). No significant prevalence differences were
      between the sexes. The frequency of age-related maculopathy was higher in eyes
      with light iris color but association was not significant. No associations were
      found between cataract or cataract type and ARM. There was no association between
      education and age-related maculopathy. Exposure to harmful work was found to be
      related to the presence of early age-related maculopathy in all. The prevalence
      of age-related maculopathy was significantly higher between men working in high
      temperature.

PMID- 14704515
TI  - [Preeclampsia and eclampsia].
AB  - Preeclampsia is a multisystem disorder after the 20(th) week of gestation, that
      is usually associated with raised blood pressure, proteinuria, and pathologic
      edema. Eclampsia is defined as the occurrence of conculsions in association with
      the syndrome of preeclampsia. In Europe and other developed countries eclampsia
      complicates approximately 1 in 2,000 deliveries, while in developing countries
      estimates vary between 1 in 100 to 1 in 1,700. 44% of seizures occur postnatally,
      the remainder being antepartum (38%) or intrapartum (18%). Although rare,
      eclampsia probably accounts for 50,000 maternal deaths a year world-wide. In this
      review article we discussed conditions, which are associated with a higher
      incidence of preeclampsia, pathophysiology, findings at physical examination,
      principles of treatment (blood pressure control, anticonvulsant therapy, and
      fluid management), post-partum management, complications, maternal morbidity and
      mortality, as well as prevention.

PMID- 14704517
TI  - Laser subepithelial keratomileusis: not just another way to spell PRK.

PMID- 14704518
TI  - Management and prevention of thin, cystic blebs.

PMID- 14704519
TI  - Surgical treatment of submacular hemorrhage in age-related macular degeneration.

PMID- 14704516
TI  - Medical and surgical management of central retinal vein occlusion.

PMID- 14704520
TI  - Selective endothelial transplantation: novel surgical techniques for the
      treatment of endothelial dysfunction.

PMID- 14704521
TI  - Prevention of aniridic glaucoma with goniosurgery.

PMID- 14704522
TI  - Macular translocation with 360-degree retinotomy for treatment of exudative age
      related macular degeneration.

PMID- 14704523
TI  - Lamellar keratoplasty revisited.

PMID- 14704524
TI  - Selective laser trabeculoplasty: stimulating the meshwork to mend its ways.

PMID- 14704525
TI  - Surgical approaches to retinal prosthesis implantation.

PMID- 14704526
TI  - Laser cataract surgery: past, present, and evolving technologies.

PMID- 14704527
TI  - New Ahmed valve designs.

PMID- 14704528
TI  - Surgical and other treatments of diabetic macular edema: an update.

PMID- 14704529
TI  - Conductive keratoplasty.

PMID- 14704530
TI  - The neuroophthalmic manifestations and treatment options of unruptured
      intracranial aneurysms.

PMID- 14704531
TI  - Injectable agents for facial rejuvenation: botulinum toxin and dermal filling
      agents.

PMID- 14704532
TI  - Lens extraction for angle-closure glaucoma.

PMID- 14704533
TI  - Review of current surgical techniques in repair of idiopathic macular holes.

PMID- 14704535
TI  - Extrapolation of animal models of optic nerve injury to clinical trial design.

PMID- 14704536
TI  - Effect of corneal drying on central corneal thickness.
AB  - PURPOSE: To determine the amount of corneal thinning induced by corneal drying,
      and to discuss its possible consequences on applanation pressure. PATIENTS AND
      METHODS: Two sets of central corneal thickness measurement from 100 eyes of 100
      patients were taken by ultrasonic pachymeter at time settings of 0, 15, 30, 45,
      and 60 seconds. During the first set (group 1), patients were asked to blink
      voluntarily between the measurements. During the second set (group 2), the same
      patients were prevented from blinking during the measurements. RESULTS: Mean
      central corneal thickness at 0 second in groups 1 and 2 were 547.0 +/- 37.4
      microm, and 546.7 +/- 37.6 microm, respectively. Corneal thickness did not change
      significantly in group 1, but did significantly decrease in group 2. Rate of
      thinning increased linearly during the first 30 seconds, and then leveled around
      0.3 microm/s up to 60 seconds. Mean corneal thickness decreased 3.0% during the
      60 second drying. The decrease in thickness was significant when each time point
      in group 2 was compared with the preceding one (P < 0.01). Neither age nor 0
      second corneal thickness in group 2 showed a significant correlation with the
      amount of corneal thinning at 60 seconds. CONCLUSION: Corneal thickness may
      significantly decrease during 1 minute of drying. Decreased thickness may result
      in underestimation of applanated pressure as well as central corneal thickness.

PMID- 14704537
TI  - Correlation between a disc hemorrhage and peripapillary atrophy in glaucoma
      patients with a unilateral disc hemorrhage.
AB  - PURPOSE: To investigate the correlation between a disc hemorrhage and
      peripapillary atrophy in glaucoma patients with a unilateral disc hemorrhage.
      METHODS: The 44 glaucoma patients (7 with primary open-angle glaucoma and 37 with
      normal-tension glaucoma) with a unilateral disc hemorrhage from June 1997 to
      November 2002 were selected randomly and included sequentially. The topographic
      measurements were performed using Heidelberg Retina Tomograph (HRT) within 3
      months of detecting the disc hemorrhage. The zone beta parameters of the
      peripapillary atrophy were analyzed by the Atrophy Zone Analysis software. The
      intraocular pressure, refractive error, visual field parameters, and optic disc
      parameters were compared between both eyes. Univariate and multivariate
      regression analysis were performed. RESULTS: The area, angular and radial extent
      of the zone beta, and the ratio of the zone beta area to the disc area were
      significantly greater in the hemorrhagic eyes than in the contralateral eyes (P <
      0.001). The prevalence of peripapillary atrophy was significantly higher in the
      hemorrhagic eyes (84%) than in the contralateral eyes (66%) (P = 0.034, chi2
      test). The rim area and the rim volume of the hemorrhagic eyes were significantly
      smaller than those of the contralateral eyes (P = 0.02, < 0.001, respectively).
      In multivariate regression analysis, the peripapillary atrophy area was the
      independent significant factor associated with disc hemorrhage (P = 0.03, Odds
      Ratio = 1.51). The refractive error, intraocular pressure, Mean Deviation (MD),
      and Corrected Pattern Standard Deviation (CPSD) of the visual fields in both eyes
      were similar. CONCLUSION: The area and extent of the peripapillary atrophy was
      significantly greater and more prevalent in the eyes with a disc hemorrhage than
      in the contralateral control eyes. Peripapillary atrophy is closely associated
      with a disc hemorrhage in glaucoma patients irrespective of small neuroretinal
      rim area and volume.

PMID- 14704538
TI  - Visual field of high-pass resolution perimetry in normal subjects.
AB  - PURPOSE: To investigate the properties of the visual field of high-pass
      resolution perimetry in normal subjects. METHODS: Four centers collected
      normative data for high-pass resolution perimetry. In two of the centers the
      subjects were stratified by age. One eye was tested per subject using high-pass
      resolution perimetry (Ophthimus). We tested 640 normal subjects and describe
      their visual field results by test location. We also analyzed the data by
      concentric zone, age, and by testing center. RESULTS: The individual test
      location averages confirmed a reduction in resolution with eccentricity.
      Resolution thresholds increased with age by 0.025 dB per year (P < 0.001). The
      mean ring size increased by about 1 dB from age 20 to 70. Among centers there
      were significant differences in the means and the change in threshold with age (P
      = 0.009). CONCLUSION: The normal visual field of high-pass resolution perimetry
      is characterized by an increase in threshold with eccentricity. We found
      significant differences among the centers that were likely due to multiple
      factors including differences in subject selection criteria. Whether such
      differences occur with other perimetric techniques is unknown.

PMID- 14704539
TI  - How well does color perimetry isolate responses from individual cone mechanisms?
AB  - PURPOSE: Over the past two decades there has been renewed interest in the use of
      color perimetry as a means of detecting early functional defects resulting from
      glaucomatous optic neuropathy and other forms of ophthalmic and neurologic
      pathology. The most popular form of color perimetry employs a colored background
      that selectively desensitizes two of the cone mechanisms, while the wavelength of
      the test target is selected to favor detection by the remaining, relatively
      unadapted, cone mechanism. While there are data to support the assertion that
      blue on yellow perimetry adequately isolates the short wavelength sensitive (SWS)
      cone mechanism, the only estimates of isolation of the other two cone mechanisms
      are for the region of the visual field corresponding to the fovea. The purpose of
      this experiment was thus to determine the amount of cone mechanism isolation that
      is afforded by automated perimetry when using yellow, blue, and magenta adapting
      backgrounds. METHODS: To estimate cone mechanism isolation, we determined
      spectral sensitivity for a range of narrow-band stimuli using a standard 30-2
      program on a modified Humphrey perimeter. Targets were presented against three
      different backgrounds of different luminance; yellow at 2.1 log cd.m-2, magenta
      at 1.3 log cd.m-2, and blue at 1 log cd.m-2. Sensitivity values for each
      background at each stimulus position were plotted as a function of wavelength,
      normalized, and then fitted with cone sensitivity templates to determine the
      relative sensitivity of the three cone mechanisms. RESULTS: The maximum relative
      isolation of an individual cone mechanism was achieved with a yellow background,
      where there was an average relative isolation of 0.94 for the SWS cone mechanism;
      the blue background provided a relative isolation of 0.89 for the long wavelength
      sensitive (LWS) cone mechanism. The magenta background proved poor at isolating
      the medium wavelength sensitive (MWS) cone mechanism, where a relative isolation
      of only 0.51 was obtained. CONCLUSION: Although color perimetry is capable of
      isolating individual cone mechanisms, the magnitude of isolation in normal
      observers may be small under certain circumstances. Therefore, when the technique
      is used to examine pathologic states, it may be necessary to employ at least two
      target wavelengths to determine the cone mechanism that is performing target
      detection. Furthermore, we suggest that MWS cone mechanism isolation may be
      improved through the combination of the so-called silent substitution technique
      with that of selective adaptation.

PMID- 14704540
TI  - Sensitivity and specificity of new GDx parameters.
AB  - PURPOSE: The GDx is a scanning laser polarimeter that assesses peripapillary
      nerve fiber layer thickness. In addition to the 14 existing outcome parameters,
      four new parameters have been described recently: the Ellipse Standard Deviation
      (ESD), the Normalized Superior Area (NSA), the Normalized Inferior Area (NIA) and
      the Discriminant Analysis (DA). The aim of this study was to investigate the
      sensitivity and specificity of these four new parameters. METHODS: Only one
      randomly selected eye of 263 healthy volunteers and 241 glaucoma patients was
      considered. The healthy group was randomly divided into a reference set (n = 132)
      to calculate the tenth percentile of the normal distribution and a test set (n =
      131) to calculate the specificity against these newly established cut-off points.
      Sensitivity was calculated for all glaucoma patients (n = 241) and again for
      three separate subgroups: early glaucoma (n = 90), moderate glaucoma (n = 93),
      and advanced glaucoma (n = 58). RESULTS: When the tenth percentile of the normal
      distribution was used as a cut-off point, the sensitivity and specificity pairs
      of the new parameters were 61.8% and 87.6%, 61.8% and 89.1%, 50.2% and 92.2% and
      72.6% and 95.3% for the ESD, NSA, NIA, and the DA, respectively. The Area under
      the ROC curve was 0.86, 0.86, 0.87, and 0.90, respectively. Among the existing
      parameters, the Number discriminated best (sensitivity and specificity: 76.8% and
      89.1%, respectively; area under the ROC curve: 0.90). When compared with The
      Number, the DA was equally good, whereas the other three new parameters performed
      statistically significantly worse. In general, the area under the ROC curve
      increased from early to moderate to advanced glaucoma. CONCLUSIONS: The new GDx
      parameters discriminated well between normal subjects and glaucoma patients. None
      of the new parameters discriminated better than The Number.

PMID- 14704541
TI  - Effect of pupillary dilation on retinal nerve fiber layer thickness measurements
      using optical coherence tomography.
AB  - PURPOSE: To evaluate the effect of pupillary dilation on retinal nerve fiber
      layer thickness (RNFL) measurements using optical coherence tomography (OCT-3).
      METHODS: Randomly chosen eyes of healthy individuals were scanned before and
      after pupillary dilation by two trained operators (R.G.O., R.V.) using OCT-3
      (Carl Zeiss Meditec, Inc., Dublin, CA). Fast and regular RNFL (256 A-scans) OCT-3
      protocols (software version A1.1) were used in each scanning session. RNFL
      thickness measurements before and after dilation were compared. RESULTS: Ten eyes
      of 10 subjects (6 females, 4 males) were enrolled. Mean age was 32.0 +/- 11.2
      years (range, 21 to 52 years). Mean pupillary diameter before and after dilation
      was 2.9 +/- 0.6 mm and 7.6 +/- 0.8 mm, respectively (P < 0.0001, paired t-test).
      There was no significant difference in RNFL thickness measurements before and
      after dilation using both fast and regular RNFL protocols (P > or = 0.05 for all
      comparisons, paired t-test). Mean coefficients of variation for mean RNFL
      thickness measurements were 15.3% before and 13.7% after dilation for operator 1;
      and 10.8% before and 12.7% after dilation for operator 2 for the fast RNFL
      protocol and 11.3% versus 10.4% and 12.9 versus 11.1%, respectively, for the
      regular RNFL protocol. CONCLUSION: Pupillary dilation is not necessary in all
      subjects to obtain reproducible RNFL thickness measurements using OCT-3.

PMID- 14704542
TI  - Baerveldt-350 implant versus Ahmed valve for refractory glaucoma: a case
      controlled comparison.
AB  - PURPOSE: To compare the efficacy of intraocular pressure (IOP) control of the
      Baerveldt-350 implant with tube ligature and the Ahmed valve in patients with
      refractory glaucoma. PATIENTS AND METHODS: Four hundred seventy glaucoma drainage
      device procedures from July 1995 to July 2001 (6 years) were reviewed
      retrospectively. Thirty-two cases of Baerveldt-350 implantation performed in
      patients with glaucoma refractory to medical treatment and filtering procedures,
      without previous drainage device or cyclodestructive procedures, and with a
      minimum of 1-year follow-up were identified. Thirty-two cases of Ahmed valve
      implantation were matched case by case with 32 Baerveldt-350 cases for age, race,
      gender, glaucoma subtype, previous ocular history, preoperative IOP, and surgeon
      who performed the implantation. The two groups were compared for IOP control,
      visual outcome, complication rate, and surgical success rate. Surgical success
      rate was defined as an IOP reduction greater than or equal to 30% and final IOP
      more than 5 mm Hg and less than 22 mm Hg, without devastating complications.
      RESULTS: Over a follow-up period of 1 year, no statistically significant
      differences were detected between the Baerveldt-350 implant versus Ahmed valve
      for IOP control (12.1 +/- 5.3 mm Hg vs. 13.6 +/- 5.6 mm Hg respectively, at a
      power of 90% to detect a difference of 3.2 mm Hg between the two groups and P =
      0.05), surgical success rate (65.6% vs. 65.6% respectively, complete and
      qualified combined), postoperative hypotony rate (37.5% vs. 34.4% respectively),
      and visual acuity changes of more than 1 line in Snellen visual acuity (43.3% vs.
      29.0% respectively). CONCLUSION: In a case-controlled comparison, the Baerveldt
      350 implant and the Ahmed valve had similar IOP control and surgical outcomes in
      patients with refractory glaucoma at 1-year follow-up.

PMID- 14704543
TI  - T-Flux implant versus Healon GV in deep sclerectomy.
AB  - PURPOSE: To compare the efficacy and safety of T-Flux implant versus Healon GV in
      deep sclerectomy. METHODS: Randomized prospective trial of 23 eyes of 20 patients
      with medically uncontrolled open angle glaucoma over a period of 24 months, who
      underwent deep sclerectomy with either Healon GV or T-Flux implant. RESULTS: Mean
      postoperative intraocular pressure was 13.2 +/- 3.0 mm Hg with T-Flux implant
      (group 1) and 12.2 +/- 3.5 mm Hg with Healon GV (group 2), with a pressure
      reduction of 53.0% in group 1 (13.2 mm Hg vs. 28.1 mm Hg) and of 48.1% in group 2
      (12.2 mm Hg vs. 23.5 mm Hg). Qualified and complete successes were 100% and 95.4%
      respectively. Pressures equal to or less than 15 mm Hg were 81.8% in group 1 and
      90.9% in group 2 with or without treatment, and 63.6% in group 1 and 81.8% in
      group 2 without treatment. The number of glaucoma treatments dropped from 2.5 +/-
      0.9 to 0.4 +/- 0.7 in group 1 and from 2.2 +/- 1.0 to 0.2 +/- 0.4 in group 2. The
      goniopuncture rate was 63.6% in group 1 and 36.4% in group 2, with a mean
      pressure drop of 6.1 +/- 3.9 mm Hg and 3.25 +/- 1.2 mm Hg respectively. Overall,
      slit-lamp diagnosed surgery-related complications included positive Seidel
      (13.6%), hyphaema (22.7%), choroidal detachment, and iris incarceration (4.5%
      each). At 2 years, ultrasound biomicroscopy showed mainly low reflective (40.1%)
      and flattened (36.4%) blebs. Principally latter ones were associated with the
      need for adjunctive treatment. A hypoechoic area in the suprachoroidal space was
      seen in at least 59.1% of eyes at 2 years and was not associated with lower
      intraocular pressure. CONCLUSION: Deep sclerectomy is an effective and safe
      surgery. However, longer follow up and larger study groups are required to assess
      the additional benefit of nonabsorbable implants.

PMID- 14704544
TI  - Repeated use of transscleral cyclophotocoagulation laser G-probes.
AB  - PURPOSE: To evaluate the energy transmission of transscleral
      cyclophotocoagulation laser G-probes after repeated use. METHODS: In this
      prospective study, eight new laser probes were each used for 30 transscleral
      cyclophotocoagulation (TSCPC) sessions in cadaver human eyes with the laser
      settings of 2000 mW power, 2000 milliseconds duration, and 18 shots. The laser
      power output was measured using a laser energy output meter before and after each
      TSCPC session, after swabbing the laser probe tip with alcohol, and finally after
      thorough cleaning by flushing 70% alcohol inside the plastic footplate tip and
      swabbing with alcohol the fiberoptic tip. Laser probes were inspected for
      deterioration. Statistical analysis was done using Analysis of Covariance
      (ANCOVA). RESULTS: The laser power output increased on average by 1.99 +/- 0.18
      mW after each cycle (P < 0.01, 95% confidence interval: 1.63-2.35 mW, ANCOVA). No
      deterioration of the probes was found after 30 TSCPC and sterilization cycles.
      Laser energy output increased on average 6% (P < 0.01) from the baseline to the
      first TSCPC cycle. Probe number one broke during the tenth cycle and accordingly
      data was recorded for this probe until that cycle. CONCLUSION: G-probes not only
      remain fully functional after repeated use and sterilization with 70% alcohol but
      also slightly increase in energy output.

PMID- 14704545
TI  - Combined viscocanalostomy and cataract surgery compared with cataract surgery in
      Japanese patients with glaucoma.
AB  - PURPOSE: To compare intraocular pressure (IOP) and the incidence of complications
      after combined viscocanalostomy and cataract surgery with cataract surgery alone
      in 206 Japanese eyes with POAG or OH. PATIENTS AND METHODS: In a nonrandomized
      comparative, clinical study, 103 eyes underwent viscocanalostomy and cataract
      surgery (VCS group), and 103 eyes underwent cataract surgery alone (CSA group)
      (follow-up, 6-24 months). Reductions in IOP and medications, the probability of
      successful IOP reduction visual acuity changes, and complications were compared
      between the 2 groups. RESULTS: The reductions in IOP and number of medications in
      the VCS group were significantly greater than in the CSA group (P < or = 0.0038
      and P < or = 0.0259, respectively). The probabilities of achieving IOPs less than
      21, 18, and 15 mm Hg at 24 months in the VCS groups were 85.0%, 53.6%, and 17.2%
      with medications, and 61.1%, 43.9%, and 16.2% without medications, and
      significantly better than in the CSA group (P < 0.0002). The visual outcomes were
      similar in both groups. Postoperative complications such as hyphema and fibrin
      formation, although more frequent in the VCS group, were not vision threatening.
      CONCLUSION: Combined viscocanalostomy and cataract surgery provides good
      postoperative visual acuity with minimal complications and significantly greater
      IOP reduction than cataract surgery alone for Japanese patients with glaucoma.

PMID- 14704546
TI  - A comparison between 90 degrees and 180 degrees selective laser trabeculoplasty.
AB  - PURPOSE: To compare two regimens of SLT, ie, SLT with 25 laser spots on 90
      degrees of trabecular meshwork and SLT with 50 laser spots on 180 degrees of
      trabecular meshwork in patients with open-angle glaucoma. PATIENTS AND METHODS:
      In a prospective clinical study, the authors compared pressure-lowering effect of
      SLT in 2 groups of patients; 1 group (32 patients) received SLT with 25 laser
      spots on 90 degrees of trabecular meshwork, the other group (32 patients) SLT
      with 50 laser spots on 180 degrees of trabecular meshwork. RESULT: There was no
      difference in the pressure reduction between these two treatment regimens.
      Moreover, the pressure reduction was not influenced by previous ALT treatments.
      The pigmentation in the trabecular meshwork is related to a delayed effect on the
      pressure lowering after SLT. CONCLUSION: SLT with 25 laser spots on 90 degrees of
      trabecular meshwork has a similar pressure-lowering effect to SLT with 50 laser
      spots on 180 degrees of trabecular meshwork. The new treatment regimen with less
      laser spots could increase the repeatability of SLT and reduce potential tissue
      damage in the trabecular meshwork.

PMID- 14704547
TI  - Increased expression of matrix metalloproteinases in mononuclear blood cells of
      normal-tension glaucoma patients.
AB  - PURPOSE: Glaucomatous optic neuropathy involves tissue remodeling by matrix
      metalloproteinases (MMPs). In this study we investigated MMP gene expression in
      circulating leukocytes isolated from normal tension glaucoma (NTG) patients in
      comparison to healthy controls. METHODS: Blood samples were collected from 6
      glaucoma patients and 6 age- and sex-matched healthy controls. Leukocytes were
      separated using Ficoll-Hypaque gradient. mRNA pools were used for subtractive
      hybridization to identify genes with altered expression. The subtracted genes
      were sequenced and individual mRNA pools were quantified using semiquantitative
      RT-PCRs. Target PCR products were confirmed using sequence-based restriction
      analysis. In this study we focused on MMPs. RESULTS: MMP-9 and MT1-MMP (MMP-14)
      were subtracted as upregulated genes in the group of NTG patients. Upregulation
      of these genes was confirmed by RT-PCR and Western-blot analysis in all 6
      patients. The expression of the tissue inhibitor of matrix metalloproteinases
      TIMP-1 was slightly enhanced in patients as compared with controls. Expression of
      MMP-2 was not detected in leukocytes either in glaucoma patients or in healthy
      subjects. CONCLUSION: A simultaneous upregulation of both MMP-9 and MT1-MMP gene
      expression and only slightly enhanced expression of TIMP-1 suggest an increased
      enzymatic matrix metalloproteinase activity delivered by mononuclear blood cells
      in these patients.

PMID- 14704548
TI  - Efficacy of bunazosin hydrochloride 0.01% as adjunctive therapy of latanoprost or
      timolol.
AB  - PURPOSE: To evaluate the ocular hypotensive response of bunazosin hydrochloride
      0.01% administered as adjunctive therapy in patients with glaucoma who were
      already receiving latanoprost 0.005% or timolol 0.5%. METHODS: Patients with
      primary open angle glaucoma who had received latanoprost (n = 60) or timolol (n =
      60) for 6 months or longer were enrolled and prospectively randomized to receive
      additional administration of bunazosin or placebo. One hundred twenty eyes of 120
      patients were thus divided into 4 subgroups of 30 patients each. Bunazosin was
      administered twice daily, and timolol or latanoprost was administered per label.
      The patients were followed up for 3 months. Responders were defined as having a
      reduction in intraocular pressure of greater than 2 mm Hg from baseline. RESULTS:
      Mean baseline intraocular pressure was 22.3 +/- 3.0 mm Hg in the bunazosin
      subgroup and 22.3 +/- 3.1 mm Hg in the placebo subgroup of the latanoprost arm,
      and 22.5 +/- 3.5 mm Hg in the bunazosin subgroup and 22.3 +/- 3.0 mm Hg in the
      placebo subgroup of the timolol arm. In the bunazosin subgroups of both arms,
      intraocular pressure was significantly reduced compared with baseline
      measurements (P < 0.05) with mean intraocular pressure measurement reductions of
      2.1 +/- 2.4 mm Hg and 2.8 +/- 2.1 mm Hg in the latanoprost arm and 2.6 +/- 2.1 mm
      Hg and 2.8 +/- 2.1 mm Hg in the timolol arm at 6 and 12 weeks after the start of
      the follow-up, respectively. In the latanoprost group, bunazosin provided a
      further reduction of intraocular pressure (7.7%) at 12 weeks from that initially
      obtained at 2 weeks (P = 0.0377). In the placebo subgroups of the latanoprost and
      timolol arms, no significant change was found between at baseline and at any
      visit after the start of the follow-up. In the latanoprost and timolol arms,
      there was a significant difference in intraocular pressure and its change between
      the bunazosin subgroup and placebo subgroup at any visit after 4 weeks from the
      start of the follow-up (P < 0.01). CONCLUSION: Bunazosin hydrochloride 0.01% may
      provide an additional intraocular pressure reduction in patients already
      receiving latanoprost or timolol. Since adding bunazosin to eyes treated with
      latanoprost caused a relatively small hypotensive response at 2 weeks and
      provided a further reduction from 2 weeks to 12 weeks, longer than 4 weeks may be
      required to evaluate a clinically meaningful response to treatment. Further
      investigation on more cases and longer follow-up are needed.

PMID- 14704549
TI  - Management of ocular hypertension.

PMID- 14704550
TI  - Myopic eyes and glaucoma.

PMID- 14704551
TI  - Generation interaction and the development of cyclical processes.

PMID- 14704552
TI  - Cutaneous distribution of infraorbital nerve.
AB  - The aim of this study is to elucidate precisely the cutaneous distribution of the
      infraorbital nerve. Ten hemifaces of five Korean adult cadavers (2 males and 3
      females) were subjected to the dissection. The cutaneous branches of the
      infraorbital nerve were distributed over the infraorbital area, which bounds on
      superiorly the lower eyelid margin, inferiorly the horizontal line crossing the
      mouth corners, medially 0.5 cm to midline, and laterally 2 cm lateral to the
      temporal canthus of the eyes. The infraorbital nerve had 19.5 branches (range, 15
      24 branches). The mean area supplied by the infraorbital nerve was 25.8 cm2
      (range, 24.0-28.2 cm2). The mean area of the superior labial branch was 13.1 cm2
      (range, 11.2-14.3 cm2) and broader than either the 7.5 cm2 (range, 6.6-8.8 cm2)
      of the lower palpebral branch or the 7.6 cm2 (range, 6.7-9.3 cm2) of the external
      nasal branch. The external nasal branch was overlapped with the lower palpebral
      and superior labial branch, but the last two branches do not overlap each other.
      The nonoverlapped branch of the infraorbital nerve exhibits a restricted
      anesthesia, but the overlapped branch sustains sensory perception to some extent
      when being damaged.

PMID- 14704553
TI  - Surgical treatment of dry eye syndrome: conjunctival graft of the minor salivary
      gland.
AB  - Despite the availability of efficient tear substitutes, many patients with dry
      eye syndrome experience severe corneal injuries and a subsequent loss of vision.
      Surgical techniques using mayor salivary glands to provide a substitute for tears
      have been reported; with this technique the drainage of saliva goes into the
      conjunctival fornix, permitting corneal and conjunctival humidification. The
      authors describe a new surgical approach in which minor salivary glands are
      autotransplanted into the conjunctival fornix by means of a graft of the
      intraoral mucosa-transporting salivary glands. This approach was used in a 56
      year-old woman with a 2-year history of refractory and pharmacologically
      untreatable dry eye syndrome caused by Sjogren's syndrome. The right eye had more
      severe corneal and conjunctival lesions than did the contralateral one, so the
      treatment was planned in the right eye only. A weekly follow-up during the first
      6 months confirmed the significant improvement of dry eye symptoms in the
      surgically treated eye. Three months after surgery, a biopsy was performed in the
      minor salivary gland graft, and the histologic findings revealed the presence of
      glandular acinus, duct with mucin content, and lymphocyte infiltration. The
      significant improvement obtained in this patient suggests that the secretion from
      the grafted salivary minor glands was better in promoting homeostasis of the
      ocular surface than are artificial tears. This may be explained by: (1) The
      lacrimal and salivary secretions contain biologically active constituents that
      may protect from infection and promote normal growth epithelium; (2) The secreted
      mucin is thought to coat the epithelial surface, reducing the high surface
      tension of the eye wetted by aqueous tears; (3) The thick secretions of the minor
      gland might act in reducing the evaporation of the underlying tear layer and form
      a hydrophobic barrier along the lid margin that can retain the lid margin tear
      string and prevent its flow onto the skin. Minor gland salivary autotransplant is
      a new surgical technique with effectiveness demonstrated in one patient, but the
      scientific explanation is not clear; additional experience with more cases could
      confirm the initial success.

PMID- 14704555
TI  - Reconstruction of a large mandibular defect utilizing temporary zygomatic-ramal
      fixation and bilateral Risdon incisions.
AB  - Ameloblastoma is a benign, invasive, odontogenic tumor of the jaws that
      predominantly affects the mandible. Despite the benign nature of these lesions,
      there is a high rate of local recurrence after curettage, which usually requires
      resection. The traditional surgical approach for resection of ameloblastomas, via
      either mandibulotomy or mandibulectomy, has been through lower lip-splitting
      incisions, which are associated with significant functional and esthetic
      sequelae. A case is presented here in which less invasive Risdon and intraoral
      degloving incisions were used in combination with temporary zygomatic-ramal
      fixation to maintain occlusion after resection of a large mandibular
      ameloblastoma. The bilateral Risdon approach provided wide access to the
      mandible, allowing an angle-to-angle resection to be performed. This approach
      also provided adequate exposure for an osteocutaneous fibula free flap
      reconstruction to be performed, with 100% flap survival. At 1 year of follow-up,
      there were minimal functional and esthetic defects. This approach represents a
      less invasive alternative that provides access to the mandible for curative
      resection of benign tumors with minimal postoperative sequelae.

PMID- 14704554
TI  - Repair of bony defect with combination biomaterials.
AB  - BACKGROUND: Numerous possibilities are available for the reconstruction of facial
      bone defects. The materials used to fill such defects must satisfy various
      requirements. One of the most important is that they must undergo transformation
      into autologous bone tissue in the process of remodeling. AIM: A report is given
      of the long-term results of augmentations of large bone defects performed with
      different bone-substitute materials in two patients. PATIENTS AND METHODS: In one
      case, augmentation was carried out with beta-tricalcium phosphate after the
      removal of a fibromyxoma. In the second case, three large cystic lesions in the
      mandible of a patient with Gorlin-Goltz syndrome were filled with beta-tricalcium
      phosphate, with a mixture of beta-tricalcium phosphate and platelet concentrate,
      or with hydroxyapatite of algal origin. The process of ossification was checked
      at 6-month intervals by means of clinical, radiologic (orthopantomograms and two
      dimensional and three-dimensional computer tomograms), and histologic methods.
      RESULTS: At 1 year after the intervention, the site of the augmentation was in
      all cases occupied by hard tissue of good quality. With the given imaging
      procedures, it was difficult to distinguish between the original bone and the
      region filled with bone-substitute material. The three-dimensional computer
      tomogram images indicated that the contours and quality of the new bone
      corresponded with the physiologic and anatomical conditions. The histologic
      examinations show the remodeling of the bone-substitute materials. DISCUSSION:
      The bone-substitute materials applied in these cases fully satisfied the demands
      of transformation into bone (remodeling). The speed of remodeling seemed to be
      the fastest when the mixture of beta-tricalcium phosphate and platelet
      concentrate was used.

PMID- 14704556
TI  - A dynamic method for stabilizing intraoral skin grafts that is simple,
      inexpensive, and effective.

PMID- 14704557
TI  - Vascular iliac crest with inner table of the ilium as an option in maxillary
      reconstruction.
AB  - Reconstruction of large maxillary defects has been a long-standing challenge to
      the reconstructive surgeon. Total maxillary reconstruction is desirable but often
      not possible; ideally, this would provide all the anatomical structural support,
      function, and esthetics missing because of the defect. A case is presented in
      which all the criteria for total maxillary reconstruction have been fulfilled.
      The patient is a 60-year-old man who had wide excision of his maxilla for
      ameloblastoma, followed by temporal bone flap reconstruction, which failed. He
      presented to our institution for further evaluation and possible treatment
      options; these were discussed with the patient and the multidisciplinary team
      that deals with congenital and acquired deformities in the head and neck area. An
      iliac crest free flap that included the inner table of the ilium based on the
      deep circumflex iliac artery was used for the reconstruction. The procedure is
      described, including restoration of a nasal lining. Osseointegrated implants were
      used for dental rehabilitation. Ameloblastoma is briefly discussed. The goals of
      maxillary rehabilitation and obstacles to obtaining those goals are presented.
      Options available for maxillary reconstruction are discussed, along with some of
      their advantages and disadvantages, as is the reason why the iliac crest free
      flap with the inner table of the ilium was chosen. An iliac crest free flap with
      microvascular anastomosis to facial vessels was used to reconstruct a large
      maxillary defect. Osseointegrated implants were used to facilitate dental
      rehabilitation. Our patient has excellent restoration of oronasal function with a
      satisfactory esthetic result.

PMID- 14704558
TI  - Posttraumatic obstruction of lacrimal pathways: a retrospective analysis of 58
      consecutive naso-orbitoethmoid fractures.
AB  - Posttraumatic dacryostenosis represent a troublesome sequela for patients who
      have sustained centrofacial trauma and can determine complexity in diagnosis and
      treatment. This article, based on a retrospective analysis of 58 patients with
      naso-orbitoethmoidal (NOE) trauma, reports the incidence of posttraumatic
      dacryostenosis and the evolution of such impairments in consideration of fracture
      type. Experience in diagnosis and treatment is illustrated, and surgical outcomes
      6 months after external dacryocystorhinostomy (DCR) are reported. Posttraumatic
      epiphora was observed in 27 patients with NOE fractures (46.5%). In 10 cases,
      temporary epiphora was encountered and spontaneous recovery of lacrimal drainage
      within 5 months was observed. In the remaining 17 cases, permanent epiphora was
      registered and a frequent association with delayed treatment of facial fracture
      repair or bone loss in the lacrimal district was found. Surgical reconstruction
      of lacrimal pathways was performed 6 months after primary surgery, with external
      DCRs in all 17 patients with epiphora and the presence of nasolacrimal duct
      obstruction observed with dacryocystorhinography. External DCR with a large
      rhinostomy achieved a success rate of 94% in the reconstruction of lacrimal
      drainage. Such a technique proved to be effective in the treatment of
      posttraumatic dacryostenosis, although patients considered the temporary presence
      of external scars and stenting material to be a major problem.

PMID- 14704559
TI  - Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold.

PMID- 14704560
TI  - Long-term results with different bone substitutes used for sinus floor elevation.
AB  - One of the surgical procedures preceding implantation is elevation of the base of
      the maxillary sinus. Numerous bone substituting materials (grafts) may be used
      for this purpose, including autogenous bone, heterografts, xenogenous bone, and
      synthetic materials alone or in combination or mixed with growth factors and bone
      morphogenetic protein (BMP) preparations. A study of the frequencies of the
      failures (graft material resorption or implant loss) after sinus elevations with
      various graft materials or their combinations was conducted. In the 5-year period
      from 1996 through 2001, a follow-up investigation of 810 maxillary sinus
      augmentations was performed, in which the sinus elevations involved the use of
      autogenous bone, a calcium carbonate-coated polymer, hydroxylapatite of algal
      origin, calcium carbonate gel produced from coral or beta-tricalcium phosphate
      alone, autogenous bone mixed with these bone substitutes, or a combination of
      beta-tricalcium phosphate and platelet-rich plasma. The incidences of graft
      resorption and implant loss after the augmentations with various bone substitutes
      were recorded. Total resorption (disappearance) of the bone substitute material
      was observed in 2.7% of the cases. An essential difference was not experienced
      between the various bone substitutes from this aspect, with the exception of the
      gel-state calcium carbonate, where 40% of the grafts were resorbed. In total,
      5.46% of the implants were lost; the differences between the various materials
      were not significant.

PMID- 14704561
TI  - Masticatory muscle right-left differences in controls and hemifacial microsomia
      patients.
AB  - One aim of this study was to assess right-left differences in the volume of
      masticatory muscles in controls so as to be able to distinguish between normal
      variations and pathological differences. The other aim was to compare the
      masticatory muscle volume of the nonaffected side of hemifacial microsomia
      patients with the smaller side of controls so as to test the compensation
      hypothesis. The study group consisted of 39 children with hemifacial microsomia
      and the control group of 52 children. Computed tomography scans were made using a
      Philips Tomoscan 350 and a Pro Speed S Fast Spiral General Electric scanner. The
      normal right-left differences in volume of the masticatory muscle of the
      controls, calculated as a percentage of the total, demonstrated small mean
      differences of 2.57% to 2.88% (SD:1.98-2.74). For hemifacial microsomia patients,
      the relative difference was about 10 times the difference for controls. For
      controls, the averages of the right-left differences (%) were all below the
      generally accepted SEM of 4%. Testing the compensation hypothesis of all effects,
      only the age effect was multivariately significant (P < 0.001). No
      overcompensation of the masticatory muscles of the nonaffected side of hemifacial
      microsomia patients could be demonstrated.

PMID- 14704562
TI  - Mandibular lengthening by distraction for airway obstruction in treacher-collins
      syndrome: the long-term results.
AB  - Mandibular lengthening by distraction was performed in a 6-year-old severely
      affected Treacher-Collins syndrome patient who was tracheostomy dependent. As
      previously reported, this procedure permitted tracheostomy removal once
      distraction was complete. Now that the patient is skeletally mature, the long
      term results of this intervention are reported with regard to his clinical
      outcome and an assessment of the anatomical changes in the upper airway during
      growth. Although the distraction could be considered a success in that it enabled
      permanent decannulation and improved the minimum cross-sectional area of the
      upper airway, there was no further increase in the minimum cross-sectional area
      of the upper airway during childhood growth. It is significant that the abnormal
      growth pattern of the mandible, which is characteristic of this syndrome, did not
      alter from its preoperative pattern once distraction was completed.

PMID- 14704563
TI  - Composite Z plasty for cicatricial ectropion of Tessier III cleft.
AB  - Tessier III clefts represent one of the most difficult and challenging
      malformations of the face to repair. Ectropion caused by a Tessier III cleft may
      be secondary to a vertical loss of both the anterior and posterior lamellae of
      the lower eyelids.A composite Z plasty to treat recurrence of cicatricial
      ectropion of the lower eyelids in Tessier III cleft is described. This is not
      only a technically easy and effective surgical method but also has a short
      operation time. To the best of the authors' knowledge, this is the first report
      of the application of a composite Z plasty in the successful treatment of
      ectropion.

PMID- 14704564
TI  - Fronto-facial monobloc advancement with rigid external distraction (RED-II)
      system.
AB  - Fronto-facial monobloc advancement is one of the most rewarding procedures for
      upper and mid-face reconstruction in patients with craniosynostosis. However, it
      has challenging aspects. Epidural abscess and frontal bone necrosis after
      retrofrontal dead space is one of the major complications and has led many
      experienced surgeons not to continue with the procedure. Bone distraction can
      play a great role in preventing these problems. The Rigid External Distraction
      (RED-II) system is a external distraction device using the cranium as an
      anchorage point. In two craniosynostosis cases, fronto-facial monobloc
      advancement with the system was performed. Controllability of the monobloc
      segment increased significantly. Operative time and blood loss were lessened. No
      major complications were experienced.

PMID- 14704565
TI  - Reconstruction of congenital absent columella.
AB  - A case of congenital absence of the nasal columella accompanying a facial
      hemangioma is presented. The nose is an important aesthetic unit of the face, and
      its projection is mainly supported by the columella. The etiology of the absent
      columella is unclear, and the clinical feature is rare. Reconstruction of the
      columella remains a challenging problem in plastic surgery, and numerous
      techniques have been described. The authors discuss several techniques aimed at
      the correction of the problem and describe a method of reconstruction of the
      absent nasal columella that was used in the case reported.

PMID- 14704566
TI  - Complications of bicortical screw fixation observed in 482 mandibular sagittal
      osteotomies.
AB  - Bicortical screw fixation after bilateral sagittal split osteotomy (BSSO) of the
      mandible is commonly used in orthognathic surgery and allows many advantages
      compared with osteosynthesis wires and maxillomandibular fixation. Complications
      include early loosening, hardware exposition, skeletal instability or early
      relapses, persistent nerve impairments, infection, and scar formation. This
      article is based on a retrospective analysis of complications of bicortical screw
      fixation observed in 241 consecutive patients with dento-skeletal Class III,
      corresponding to 482 sides, during the immediate postoperative period and at 1,
      3, 6, and 12 months' follow-up. In the immediate postoperative period, poor
      stability of fixation caused by screw loosening was observed in 3 of 482 (0.62%)
      sides; at the 1-month follow-up, infections were encountered in 12 (2.48%) sides
      at mandibular angles. Additional complications were not seen in the series.
      Stability of fixation was found in the 482 sides at 12 months. However,
      complications directly related to bicortical screws were observed in 15 sides or
      3.11%. Age and gender of patients were not correlated with the incidence of
      complications. Assiduous follow-up during the early postoperative period and 1
      and 2 months after surgery is recommended in patients with bicortical screw
      fixation after BSSO to verify adequate oral hygiene and provide early observation
      of the onset of any infections, skeletal instabilities, or relapses.

PMID- 14704567
TI  - Treatment of the unilateral cleft lip nasal deformity.
AB  - The lack of tip projection on the affected side of a unilateral cleft lip nasal
      deformity can be difficult to correct due to lack of adequate structural support.
      A new technique for the correction of the unilateral cleft lip nasal deformity is
      described. The key components of the technique involve the use of a dorsally
      angulated unilateral spreader graft on the cleft side and the use of an L-shaped
      septal graft to provide support to the cleft nasal tip.

PMID- 14704568
TI  - Anesthetic concerns of external maxillary distraction osteogenesis.
AB  - BACKGROUND: External maxillary distractions present additional anesthetic
      concerns to the existing complexity of the patient with craniofacial disorder.
      The distraction hardware is rigidly fixed to the cranium and projects in the
      frontofacial midline, thus limiting oronasal airway access. METHODS: A review of
      16 patients (10 male, 6 female) having external maxillary distraction was done.
      Patients with patent tracheostomies were excluded. In all cases, the same type of
      external distraction device was used (R.E.D., K.L.S. Martin, Jacksonville, FL,
      USA). Perioperative records were reviewed for medical history; operative
      diagnosis, presence of airway disease, tracheostomy, laryngoscopy grade, use of
      fiberoptic bronchoscope, procedure, operative time, use of intraoperative
      steroid, day of postoperative extubation, and need for reintubation were
      documented. RESULTS: The study group was subdivided into two diagnostic
      categories: those with syndromic craniosynostosis (n = 9) and those with cleft
      lip/palate (CLP) (n = 7). Patients in the craniosynostotic group had grade 1
      laryngoscopy views, with the exception of a single patient with Crouzon syndrome
      who had a grade 3 view. This was the only patient who required fiberoptic
      intubation. One patient with Apert syndrome required reintubation (48 hours after
      surgery); successful extubation was done 96 hours later. In the cleft lip/palate
      group, all patients had grade 1 laryngoscopic views, except one with a grade 3
      view; no patient required fiberoptic intubation. Six of the seven patients were
      extubated immediately after surgery, with one patient extubated the next day. No
      patient experienced failure of extubation. CONCLUSIONS: External maxillary
      distraction minimally affects anesthetic management provided certain safeguards
      are observed. The vertical bar can be left attached to the cranial portion of the
      distractor, or it can be removed for extubation or reintubation. Removal of the
      vertical bar allows unobstructed direct laryngoscopy. This emphasizes the
      importance for the emergent availability of the appropriate screwdrivers and wire
      cutters to remove the vertical bar and trained personnel to perform the removal.

PMID- 14704569
TI  - Soft tissue hemangioma formation within a previously excised intraosseous
      hemangioma site.
AB  - Intraosseous hemangiomas are rare benign lesions, occurring often in verbrata and
      skull. These lesions can present in the head and neck region being the next most
      common site with a predominance of the mandible. Herein we report a patient who
      experienced a soft tissue hemangioma occurring at the previous surgical site
      three years after the first operation.

PMID- 14704570
TI  - Treatment of bilateral symptomatic enophthalmos associated with weight loss.

PMID- 14704571
TI  - Communication of infraorbital nerve and facial nerve: anatomic and histologic
      study.
AB  - The maxillary nerve, second division of the trigeminal nerve, is entirely
      sensory. It has been reported that drooling may occur later in the event of
      fracture of the zygoma in which hypesthesia prevails. The aim of the study is to
      elucidate additional detailed anatomy of the infraorbital plexus, consisting of
      the superior labial branch of the infraorbital nerve and facial nerve in the
      cheek. The authors dissected infraorbital nerves and facial nerves in 16
      cadavers. Most terminals of the zygomatic branch of the facial nerve emerged from
      under the levator labii superiors and zygomatic muscle and infraorbital nerve. A
      hazardous zone of infraorbital plexus is found in a circle 36 mm in diameter. Its
      center is located 22 mm below the inferior orbital foramen. This hazardous zone
      of infraorbital plexus should be kept in mind when performing any procedures
      related to zygoma, maxilla, or deep cheek injuries.

PMID- 14704572
TI  - Successful free osteocutaneous scapular flap transfer for mandibular
      reconstruction in a 93-year-old patient.
AB  - With the extension of the average life span and the development of surgical
      technique, anesthesia, and pre- and postoperative management, operations for
      elderly patients have become more widely accepted. In the field of plastic
      surgery, free-flap transfers using microvascular techniques have become a common
      surgical procedure in reconstruction of the head and neck region after surgical
      removal of a cancer. There have been several reports of free-flap transfer in
      patients older than 90 years, but the authors know of no reports of free
      osteocutaneous flap transfer for mandibular reconstruction, which is a very
      invasive free-flap surgery, for such patients. The mandible plays a significant
      role in various kinds of dynamic functions, such as mastication, deglutition, and
      articulation. Disorder of these functions causes a deterioration in the patient's
      quality of life. The authors have performed a mandibular reconstruction using an
      osteocutaneous scapular free flap after resection of a gingival cancer invading
      the mandibular bone in a 93-year-old Japanese woman. In our case, an
      osteocutaneous scapular free flap, which permits the patient rapid rehabilitation
      of the lower leg, is thought to be a good choice because it allows the patient to
      get out of bed as quickly as possible in the postoperative period to minimize
      additional complications.

PMID- 14704573
TI  - Endoscopic assistance in the removal of a foreign body in the condylar process.
AB  - This case report describes the application of the endoscopic technique in the
      removal of a metallic foreign body in the condylar process in an 81-year-old man.
      The patient's history indicated 60 years of pain in the left preauricular region
      as well as complaints of localized headaches. Physical examination revealed
      multiple scars on the patient's left preauricular region. No limitation of
      mandibular movement and no joint clicking were detected. Maximal mouth opening
      was 45 mm. According to the patient, masticatory function was normal. Digital
      palpation of the temporomandibular joint did not produce pain. Radiographic
      diagnosis was performed, which showed a pointed metallic foreign body lodged in
      the left condylar process. The removal of the foreign body was performed under
      endoscopic visualization via an intraoral approach. A 30 degrees-angled 4-mm
      diameter endoscope (Karl Storz, Tuttlingen, Germany) with a xenon light source
      was used.

PMID- 14704574
TI  - Nasal augmentation using calcium phosphate cement.
AB  - This report describes a simple technique for augmentation rhinoplasty using
      calcium phosphate cement paste for postoperative and posttraumatic nasal
      deformities. This biomaterial was used to correct traumatic nasal bone deformity
      in one patient and for augmentation rhinoplasty after removal of the nasal
      implant in two patients. These patients were followed for a minimum 6 months and
      a maximum of 26 months. The esthetic results were satisfactory with no
      complication. Calcium phosphate cement consisting of alpha-tricalcium phosphate,
      dicalcium phosphate dibasic, and tetracalcium phosphate monoxide has been used
      for bone replacement and augmentation because of its good biocompatibility and
      osteoconductivity. This technique is easy and safe. It seems to be a suitable
      material for augmentation rhinoplasty in the Orient. Its long-term safety and
      reliability require proof with longer follow-up periods, however.

PMID- 14704575
TI  - Surgical treatment of recurrent orbital hemangiopericytoma.
AB  - Hemangiopericytoma is a rare vascular tumor featuring the uncontrolled
      proliferation of pericytes. This tumor tends to develop in subcutaneous tissue
      and skeletal muscle. The localization of hemangiopericytoma in the orbit is
      particularly rare. Clinical signs and symptoms are, in order of frequency,
      proptosis, perception of an intraorbital mass, pain, diplopia, reduction of
      visus, tumescence, and ecchymoses of the eyelids. Hemangiopericytomas have higher
      potential of relapse, local invasiveness, and the possibility of producing
      distant metastases. Surgery must be as radical as possible to avoid incomplete
      tumor resection and high frequency of relapse together with increased duration of
      the disease and a higher risk of malignant development. The current report is a
      study of two cases of hemangiopericytoma in the orbital cavity treated at the
      Unit of Maxillo-Facial Surgery of the University of "La Sapienza" in Rome. The
      present data demonstrate that complete en bloc excision of the mass with its
      capsule is important to avoid the risk of relapse. To this end, an appropriate
      first surgical treatment should be chosen so as to obtain a wide "surgical light"
      and complete view of the mass. In the reported cases, the use of a combined
      anterolateral approach was preferred to attack the tumor from different sides.
      Indeed, such an approach allows one to obtain optimal exposition of the orbital
      region and temporal and infratemporal fossae contemporaneously.

PMID- 14704576
TI  - The vascular anatomy of the digastric muscle.
AB  - There are plenty of flaps for the reconstruction of defects of the head and neck
      region. In the literature, local muscle and myocutaneous flaps such as
      sternocleidomastoid, pectoral, and deltopectoral flaps are proposed for
      obliteration of pharyngocutaneous fistulas. Restoration of facial nerve palsies
      in which nerve repair and nerve grafting are not feasible is accomplished by
      means of regional muscle transpositions. The vascular anatomy of the digastric
      muscle to be used in such instances is investigated after latex application to 18
      neck regions of nine cadavers. The dissection continued anteriorly from the
      origin of the facial artery to the end of the submental artery, preserving all
      the branches piercing and nourishing the muscle. The submental artery courses
      over the posterior surface of the anterior belly of the digastric muscle, giving
      off the major pedicle of the muscle 1 cm after exiting behind the submandibular
      gland. The submental artery gives off another branch, the first minor pedicle of
      the muscle distal to the major pedicle at a distance of two thirds of the muscle
      length in a standard fashion in all the cadavers. The artery ends in the distal
      portion of the muscle, the second minor pedicle of the muscle. The artery gives
      off periosteal branches to the mandible after coursing through the insertion
      muscle. The anterior belly of the digastric muscle could be classified as a type
      II muscle, with a major pedicle and two minor pedicles, according to the system
      of Mathes and Nahai. The anterior digastric muscle can be a good alternative in
      obliteration of pharyngocutaneous fistulas, and defects of the mandible,
      including the body and angle of the mandible, can be amended with the split
      mandibular myo-osseous digastric flap.

PMID- 14704577
TI  - Molding helmet therapy in the treatment of brachycephaly and plagiocephaly.
AB  - The purpose of this study was to compare the use of molding helmet therapy in the
      treatment of positional brachycephaly and posterior positional plagiocephaly.
      Four hundred twenty-eight children with positional brachycephaly or plagiocephaly
      were included in this study. In this group of patients, 132 (32%) were treated
      with positioning alone. Of the 292 (68%) patients who were treated with molding
      therapy, 64 (21.9%) were treated for positional brachycephaly and 248 (78.1%)
      were treated for posterior positional plagiocephaly. All children were evaluated
      by a craniofacial surgeon and a pediatric neurosurgeon. Anthropomorphic
      measurements were used to assess the efficacy of treatment. Measurements were
      made before initiation of therapy and at 2-month intervals until the completion
      of therapy. Results showed that statistically significant improvements (P < 0.01)
      were seen in all patients treated with molding helmet therapy. Overall, the
      children with posterior plagiocephaly normalized their head shapes; however, the
      head shapes of the children with positional brachycephaly did not normalize
      despite statistically significant improvements in their Cephalic Index. It is
      concluded that molding helmet therapy is an effective treatment of position
      induced head shape abnormalities. Helmet therapy is more effective in children
      with posterior positional plagiocephaly than in children with positional
      brachycephaly.

PMID- 14704578
TI  - New internal Le Fort I distractor for the treatment of midface hypoplasia.
AB  - A new Le Fort I internal distraction device was developed by one of the authors
      (J. G.) and successfully used on a patient with cleft lip and palate and severe
      maxillary hypoplasia. The device consisted of an upper plate and a lower plate,
      which were installed above and below the Le Fort I osteotomy. The upper plate was
      shaped like a "U," and the lower plate was shaped like an inverted "U." The
      design of the device was unique in that the distraction screws were placed in the
      maxillary sinus and orientated parallel to the sagittal plane. Presurgical
      planning used a stereolithographic (STL) model and the CASSOS software to
      calculate the distraction vector. The distractors were prebent and installed on
      the STL model and activated to advance the maxilla 15.5 mm. Surgery was performed
      in a conventional manner, and distraction was started on the seventh day after
      surgery. At the completion of distraction, a total of 15.5 mm of distraction was
      achieved. The distractors were removed 3 months after surgery. Results showed
      that the patient's severe maxillary hypoplasia was corrected as predicted and
      there was excellent new bone formation between the edges of the osteotomy.

PMID- 14704579
TI  - Perception of symmetry in the face.
AB  - One purpose of this study was to assess the perception of (a)symmetry of the face
      by professionals, lay persons, and sculptors using the ratio estimation scale
      technique. The other purpose was to compare the perceptions of the faces of
      patients with those of the controls. Three groups of examiners were involved in
      this study: lay persons (n = 37), professionals (5 orthodontists and 11 surgeons,
      n = 16), and sculptors (n = 22). The total number of examiners was 75. All groups
      agreed on the ordering of the patients according to the severity of the
      affliction. The stage of asymmetry by group identity interaction effect (lay
      persons, professionals, and sculptors) was significant (P = 0.004). The between
      examiner consensus was high for the original asymmetrical photograph, but the
      groups diverged further and further over the next steps. The subject identity by
      stage of asymmetry interaction effect was significant (P = 0.001), whereas the
      examiner's main effect was not. For all patients, each step resulted in a smaller
      need for treatment. A need for treatment was not found for any of the control
      subjects, with 1.5 being the highest need for treatment score for controls. The
      subject identity effect (patient/control) was significant (P < 0.001). Even at
      step 5 (the reconstructed symmetrical photograph), all patients were perceived to
      have an inferior appearance to that of control subjects. It is possible to obtain
      reliable assessment using the ratio estimation scale technique. Professionals,
      lay persons, and sculptors have different perceptions of the degree of asymmetry
      but not of the need for treatment. All patients were scored as asymmetrical
      compared with controls. Asymmetry of the patients was obvious for all the
      examiners.

PMID- 14704580
TI  - Distraction osteogenesis of the cranial vault for the treatment of craniofacial
      synostosis.
AB  - From January 2000 to December 2001, six patients with craniosynostosis were
      treated. Involved sutures were coronal sutures in three patients, coronal and
      metopic sutures in one patient, multiple sutures (brachycephaly and oxycephaly)
      in one patient, and multiple sutures with a cloverleaf skull deformity in one
      patient. The age distribution of the patients was 4 months to 3 years. Four were
      male, and two were female. A frontal craniotomy was performed in four patients
      with brachycephaly. In one patient with brachycephaly, the osteotomies were made
      across the nasofrontal junction, across the roof of the orbit, and along the
      lateral orbital wall. In one patient with a cloverleaf skull deformity, a frontal
      bone osteotomy was first performed 1 cm above the roof of the orbit. A
      supraorbital frontal bar was then made across the nasofrontal junction, across
      the roof of the orbit, and down to the lateral orbital wall. The frontal bone
      flap was repositioned to the supraorbital bar using absorbable miniplates and
      screws. Distraction was started 3 to 7 days after the operation at a distraction
      rate of 1 mm/d. The real duration of the first operation was 90 to 120 minutes,
      and the second operation to remove the device took 40 to 50 minutes to perform.
      The distracted length was 15 to 25 mm. The consolidation period was 3 to 5 weeks.
      The follow-up period was 6 months to 1 year. Postoperative three-dimensional
      computed tomography demonstrated reossification at the bone flap and advancement
      of the fronto-orbital area. After surgery, the cranial volume increased 22.7% on
      average compared with before surgery. The mean ratio of the anteroposterior
      length to the transverse length of the cranial vault was changed from 0.96 before
      surgery to 1.04 after surgery. In conclusion, the advantages of distraction
      osteogenesis of the cranial vault are that it offers a less invasive technique, a
      shorter operation time, easy care, and postoperative safety as a result of
      minimal dissection of the dura. Disadvantages are the limited possibility of
      initial reshaping and the necessity of one more operation for device removal.

PMID- 14704581
TI  - Surgical timing in orbital fracture treatment: experience with 108 consecutive
      cases.
AB  - Orbital fractures can lead to esthetic deformities and functional impairments,
      and adequate surgical timing is considered important in obtaining good results
      from surgery. By means of chart review, a retrospective analysis was carried out
      in 108 consecutive cases of pure orbital fractures to investigate the differences
      in surgical timing and the correlations with patient age and clinical and
      radiographic findings. In this analysis, surgical timing of pure orbital
      fractures was strongly related to the combination of parameters such as
      anatomical location of the fracture, eventual exposure of the fracture,
      cerebrospinal fluid (CSF) leakage or penetrating wounds, age of patients,
      eventual functional impairments or muscle entrapment, and serious conditions of
      compression or ischemia. As the data confirmed, an urgent approach was considered
      indispensable in severe orbital apex fractures and in orbital fractures with CSF
      leakage, penetrating objects, or exposure. Early surgery was necessary within 3
      days in children with diplopia (type IIIb) and mainly within 7 days in adults
      with double vision (type IIIa). Delayed surgery, within 12 days in all cases, was
      performed orbital wall fractures with no impairments (type II) or in orbital rim
      fractures (type I). Data from this retrospective analysis confirm the need for an
      aggressive approach to all orbital fractures. In our experience, surgery was
      performed within 12 days and most orbital fractures were treated during the first
      week after trauma, which is earlier than previously reported.

PMID- 14704582
TI  - Condition variables in children with craniofacial anomalies: a descriptive study.
AB  - The objective of the study is to describe the prevalence of a number of condition
      variables and their interrelations in children with craniofacial anomalies
      (CFAs). The participants were 217 children with CFAs (125 boys and 92 girls),
      aged 5 to 16 years. The medical files and brain imaging provided information on
      most condition variables except for the variable phenotypical expression, on
      which information was obtained in a rating experiment. Brain anomalies were
      present in 77 subjects (36%), absent in 79 subjects (36%), and undefined in 61
      subjects (28%). Craniosynostosis occurred in 160 children (74%), a syndromic
      diagnosis in 108 (50%), and clinical hypertelorism in 72 (33%). The mean
      phenotypical expression score was 4.8 (SD = 2.1), the mean number of
      hospitalizations was 6.2 (SD = 5.6), and mean age at craniotomy was 10.9 months
      (SD = 9.3). Many of the condition variables were significantly interrelated.
      Brain anomalies occur frequently (36%) in syndromic and nonsyndromic forms of
      CFAs. The most salient condition variables are the presence of brain anomalies, a
      syndromic diagnosis, clinical hypertelorism, a severe phenotypical expression,
      and female gender. Individuals presenting with one or more of these condition
      variables probably form the most severely affected group and require more
      treatment.

PMID- 14704583
TI  - Nasalance measures in German-speaking cleft patients.
AB  - The purpose of this study was to evaluate nasalance measures in German-speaking
      patients with different types of repaired cleft lip and palate and to find out if
      significant nasalance gender differences exist in the different cleft groups. A
      total of 125 German-speaking cleft patients (74 male and 51 female) were included
      in this study: 18 patients with isolated unilateral cleft lip (UCL; mean age:
      13.00 +/- 2.03 years), 66 patients with complete unilateral cleft lip and palate
      (UCLP; mean age: 14.80 +/- 3.45 years), 25 patients with isolated cleft palate
      (CP; mean age: 14.60 +/- 3.48 years), and 16 patients with complete bilateral
      cleft lip and palate (BCLP; mean age: 14.30 +/- 3.61 years). Nasalance data were
      collected and computed using the NasalView hardware/software system (Fa. Tiger
      Electronics, Seattle, WA). Speech stimuli according to a modified Heidelberg
      Rhinophonia Assessment Form (sustained vowels "a," "e," "i," "o," and "u"; oral
      and nasal sentences; and three oral-nasal reading passages) were used to obtain
      nasalance scores. Nasalance distance and ratio were also calculated for the oral
      and nasal sentences and for one of the oral-nasal reading passages. Unpaired t
      tests showed no significant gender nasalance differences in each cleft group.
      Analysis of variance showed no significant differences in mean nasalance distance
      and ratio. For the nasal sentence, a significant difference (P = 0.032) in mean
      nasalance scores was found between the UCL and UCLP groups.

PMID- 14704584
TI  - Bilateral parotid voluminous masses: a case report.
AB  - The case of a 75-year-old woman with voluminous bilateral symmetrical masses of
      the parotid glands is reported, and the literature relevant to the differential
      diagnosis in bilateral neoplastic and nonneoplastic parotid masses is reviewed.
      The presurgical workup was based on clinical evaluations, nuclear magnetic
      resonance imaging findings, and cytologic examination to obtain the differential
      diagnosis. Benign or malignant tumors were excluded. Surgery was performed for
      esthetic reasons and in consideration of progressive enlargement of lesions.
      Histopathologic examination of resected masses revealed benign lymphoepithelial
      cysts with polyclonal infiltration of lymphoid cells. Serological testing for
      tuberculosis, cytomegalovirus, human immunodeficiency virus, and Epstein-Barr
      virus (EBV) and testing using the in situ hybridization technique for the
      presence of cytomegalovirus and EBV were negative for productive infection or
      viral replication. A diagnosis of retention cysts was suspected on the basis of
      presurgical evaluation, histopathological examination, and serologic analysis. In
      this case, bilateral obstruction of the parotid ducts by a mobile denture
      probably played the main role in the pathogenesis and development of bilateral
      parotid retention cysts, because any other specific cause for the pathogenesis
      was not found with diagnostic tools.

PMID- 14704585
TI  - An international surgical exchange program for children with cleft lip/cleft
      palate in Manaus, Brazil: patient and family expectations of outcome.
AB  - Increasingly, surgeons are traveling from the developed to the developing world
      to volunteer their services. They can often make an enormous difference in the
      lives of patients they serve, but they must understand that these patients exist
      in a sociocultural matrix in which the meaning of the condition they have and the
      future they face are determined by a host of factors over and above the specific
      surgery itself. This means that programs in which teams quickly go in and out of
      a country must take into account and plan for longer term follow-up by colleagues
      within that country as well as develop and target rehabilitation services and
      educational messages to ensure maximum benefits from the intervention performed.
      This study examines the long-term implications of a short-term surgical team
      intervention for pediatric patients with cleft lip/cleft palate and their
      families in the Amazon region of Brazil.

PMID- 14704587
TI  - Therapeutics 2004.

PMID- 14704586
TI  - Development of a new three-dimensional cranial imaging system.
AB  - The development of a new three-dimensional (3D) imaging system designed to obtain
      a digital image of an infant's cranium is described. This system is intended to
      replace the manual plaster-casting technique currently used during the process of
      fabricating cranial remodeling bands. The system uses 18 triangulated digital
      cameras and the projection of random infrared patterns to capture a 360 degrees
      image of an infant's cranium instantaneously, including the face and top of the
      head. Accuracy was calculated by comparing models digitized with this system with
      the same models digitized with high-precision inspection equipment. Safety was
      documented under guidelines established by the American Council of Governmental
      Industrial Hygienists. Images were acquired in 0.008 seconds and processed for
      viewing in software within 2.5 minutes. Accuracy was calculated to be +/-0.236
      mm. Hazard analysis confirmed the system to be safe for direct continuous
      exposure. The data acquired may be viewed as a point cloud, wire frame, or
      surface on which a digital photograph (ie, texture) is automatically overlaid.
      Physical models are created by exporting the digital data to a multiaxis milling
      machine or stereolithography machine. Quantitative data (linear and surface
      measurements, curvature, and volumes) can be obtained directly from the digital
      data. The cranial imaging system is a safe and accurate method of obtaining
      digital 3D images of an infant's cranium. Along with the obvious clinical and
      manufacturing benefits, it also has significant potential as a research tool for
      documenting the natural history and evaluating the treatment of plagiocephaly.

PMID- 14704588
TI  - Should statins go OTC.

PMID- 14704589
TI  - A cost analysis of fondaparinux versus enoxaparin in total knee arthroplasty.
AB  - Several hundred thousand total knee replacement (TKR) surgeries are performed in
      the United States each year. The American College of Chest Physicians has
      classified TKR patients in the "highest-risk" category for developing venous
      thromboembolic events. Recommended prophylactic agents following TKR surgery
      include unfractionated heparin and low-molecular weight heparins. Fondaparinux is
      a selective inhibitor of factor Xa and has recently received approval for the
      prophylaxis of venous thromboembolism in TKR patients. In November 2001, an
      efficacy study comparing fondaparinux with enoxaparin as deep vein thrombosis
      prophylaxis in TKR surgery was published by Bauer et al. The purpose of the
      current study was to perform an incremental cost analysis for fondaparinux versus
      enoxaparin using the efficacy and safety data of the Bauer et al study. Specific
      comparisons evaluated included cost per venous thromboembolic event avoided, cost
      per death averted, and cost per life-year gained with fondaparinux and
      enoxaparin. All analyses were performed from an institutional perspective and
      projected to 1000 patients. The incremental cost analysis indicates an USD
      $1081.33 cost savings with fondaparinux over enoxaparin per venous thromboembolic
      event avoided. Cost per death averted in the enoxaparin group is USD $88,943.54;
      cost per death averted in the fondaparinux groups is USD $81,157.94. Cost per
      life-year gained of USD $5437 for enoxaparin and USD $4925 for fondaparinux.

PMID- 14704590
TI  - Economic analysis of sildenafil citrate (Viagra) add-on to treat erectile
      dysfunction associated with selective serotonin reuptake inhibitor use.
AB  - The objective of this study was to compare the economic cost of adding sildenafil
      citrate (Viagra, Pfizer Inc., New York, NY) to treat selective serotonin reuptake
      inhibitor (SSRI)-induced erectile dysfunction with that of discontinuing
      antidepressant pharmacotherapy, switching patients to another SSRI, or adding a
      non-SSRI. Based on our real-world experience in an academic medical center, we
      performed an economic analysis of a hypothetical cohort of 1000 patients taking
      SSRIs on a course of acute and continuation treatment recommended by the American
      Psychiatric Association. We used standard costing of antidepressants, sildenafil,
      and unit costs for physician visits within a managed care environment and cost-of
      illness methodology to calculate the annualized cost of depression for different
      treatment outcomes. After 6 months of SSRI treatment, the sildenafil add-on group
      had the lowest cost estimates compared with groups that discontinued SSRIs,
      substituted another SSRI (switching), or added a non-SSRI to the existing SSRI
      (augmentation). Sensitivity analyses demonstrated that the physician visit was
      the single most important cost component in this hypothetical population and
      relapse/remission the most costly outcome. Sildenafil can be a cost-effective add
      on therapy to control SSRI-induced erectile dysfunction. Healthcare payors should
      consider this when developing optimum treatment strategies for men with
      depression.

PMID- 14704591
TI  - Effect of pefloxacin on the urinary excretion of rifampicin.
AB  - The effect of pefloxacin on the urinary excretion of rifampicin was investigated
      in 5 healthy volunteers between the ages of 20 and 35 years. The investigation
      was carried out in 2 different phases, with a 1-week drug washout separating the
      phases. Each subject received 600 mg rifampicin with 350 mL of water. After 1
      week, the subjects were given 600 mg rifampicin plus 500 mg pefloxacin with 350
      mL of water. Urinary levels of rifampicin were measured spectrophotometrically
      for the 2 phases from 0 to 72 hours. Coadministration of rifampicin with
      pefloxacin led to 20.1% urinary recovery of rifampicin. The increased rifampicin
      excretion rate following pefloxacin coadministration is supported by the
      competitive liver clearance between rifampicin and pefloxacin, which favors
      pefloxacin and causes rifampicin secretion, thus increasing its elimination
      through the kidney. Pefloxacin increases the absorption and urinary excretion of
      rifampicin by decreasing the gastrointestinal motility through chelation
      mechanisms.

PMID- 14704592
TI  - Nonselective nonaspirin nonsteroidal anti-inflammatory drugs and gastrointestinal
      bleeding: relative and absolute risk estimates from recent epidemiologic studies.
AB  - Gastrointestinal bleeding (GIB) is known to be associated with use of
      nonselective nonaspirin nonsteroidal anti-inflammatory drugs (NNANSAIDs), but it
      is less clear whether and to what extent variation in GIB risk exists according
      to the characteristics of exposure. To assess the consistency of data on the
      relative and absolute risks of GIB among NNANSAID users, we reviewed
      epidemiologic studies conducted around the world for data on NNANSAID use
      categorized by dose, timing, and type of exposure. US mortality rates for GIB
      were obtained and used to estimate national rates of GIB death attributable to
      NNANSAID use in the 1990s. The average relative increase in risk of GIB among
      NNANSAID users was found to be fourfold or slightly higher, regardless of the
      demographic characteristics of the studied population. There were approximately
      twofold increases associated with over-the-counter doses and sixfold or higher
      increases at heavy prescription levels. Variation in risk exists by type of
      NNANSAID, although differences by preparation seem at least partly dose-related.
      GIB risk declines following cessation of NNANSAID use, with current rather than
      prior cumulative exposure the key determinant of risk. The baseline rate of GIB
      in all studied populations rises markedly with advancing age. Annual
      hospitalization rates for GIB exceed one per 1000 among the elderly, with the
      large majority of cases occurring among persons age 65 years and older. NNANSAID
      use may account for nearly 34% of all GIB cases in the United States, and may
      have resulted in over 32,000 GIB hospitalizations and 3200 GIB deaths per year in
      the 1990s.

PMID- 14704593
TI  - Patient characteristics and risks factors for development of dependence on
      hydrocodone and oxycodone.
AB  - The purpose of the study was to document the substantial increase in problematic
      use of hydrocodone and oxycodone in an addiction treatment population. Our study
      consisted of a retrospective review of medical records from all patients admitted
      and discharged in 2000 from Sparrow/St. Lawrence Addiction Detoxification Unit (N
      = 534). A literature review was conducted in medical journals, governmental
      groups, and reports including Drug Abuse Warning Network, Pharmacy Times, and
      National Household Survey on Drug Abuse. More than 144 patients (27%) were
      dependent on prescription opiate medications. The most frequently mentioned
      medication was Vicodin (hydrocodone) (53% of the users) followed by OxyContin
      (oxycodone) (19%). Physicians commonly prescribed these medications (75% of the
      cases). Predictors of dependence on opiate medications included substance-related
      diagnoses, positive toxicology for opiates, and other medical diagnoses. Patients
      under the care of physicians who have other drug dependence diagnoses and medical
      complaints appear at risk of developing dependence on prescription opiate
      medications. Proper evaluation and intervention can limit adverse consequences of
      prescription opiate medications.

PMID- 14704594
TI  - Enhancement of myocardial vulnerability by atrial fibrillation.
AB  - Certain groups are known to have an increased risk for sudden cardiac death.
      Epidemiologic studies have suggested that patients with atrial fibrillation may
      be at higher risk. The authors hypothesize that atrial fibrillation may increase
      myocardial vulnerability. To test this hypothesis, 37 dogs were studied using
      programmed electrical stimulation techniques to determine myocardial
      vulnerability as assessed by the ability to provoke ventricular tachycardia.
      Prior to atrial fibrillation, programmed electrical stimulation did not induce
      ventricular tachycardia. Aconitine was then topically applied to the right atrial
      appendage with care taken not to make contact with the ventricle. Application of
      aconitine caused atrial fibrillation with an increase in ventricular rate, but
      did not affect arterial blood pressure. Ventricular tachycardia was induced by
      programmed electrical stimulation studies in 25 of 26 dogs in atrial
      fibrillation. The enhanced vulnerability was noted following atrial fibrillation,
      not after aconitine application to the great veins, which did not cause atrial
      fibrillation. To further exclude the possibility that aconitine application may
      cause changes in ventricular threshold, atrial fibrillation was induced by pacing
      techniques in five dogs. Prior to atrial fibrillation induction, programmed
      electrical stimulation did not induce ventricular tachycardia. Following atrial
      fibrillation, ventricular tachycardia could be repeatedly induced. Mean heart
      rate following atrial fibrillation increased, while pacing animals at this
      increment in rate did not change the noninducibility of dogs in sinus rhythm. Six
      patients with a history of atrial fibrillation and ventricular tachycardia were
      studied to determine if AF lowered myocardial threshold to VT induction.
      Ventricular tachycardia could only be induced by PES techniques in four of five
      patients when the patients' rhythm was AF (P < 0.05). This study suggests that
      atrial fibrillation lowers myocardial threshold for ventricular tachycardia
      induction and thus enhances myocardial vulnerability. The association of AF with
      a higher incidence of sudden death may be due to an enhanced electrical
      instability.

PMID- 14704595
TI  - Renin-angiotensin system as a therapeutic target in managing atherosclerosis.
AB  - Clinical and experimental evidence suggests that the pathways by which
      hypertension and dyslipidemia lead to vascular disease may overlap and that
      angiotensin II (Ang II) is involved in restructuring of the arterial wall in both
      atherosclerosis and hypertension. Ang II represents a potent proinflammatory
      agent promoting recruitment of monocytes into the vascular intima. Ang II also
      indirectly facilitates transformation of macrophages and smooth muscle cells into
      foam cells by promoting superoxide radical formation (via NADP/NADPH oxidase
      stimulation). The oxidative stress produced by Ang II leads to enhanced low
      density lipoprotein oxidation and degradation of nitric oxide, an important
      vascular protective molecule capable of retarding atherosclerosis progression.
      The importance of the renin-angiotensin system (RAS) in atherogenesis is
      highlighted by studies in animal models as well as human beings indicating that
      inhibition of angiotensin-converting enzyme or blockade of type 1 Ang II
      receptors retards the development of atherosclerotic lesions. In light of a
      causal and central role of Ang II in atherogenesis, blockade of the RAS
      represents an important therapeutic consideration in the prevention and treatment
      of atherosclerotic disease.

PMID- 14704596
TI  - Optimizing LDL-C lowering with statins.
AB  - Clinical studies have demonstrated the efficacy of statins in reducing low
      density lipoprotein cholesterol (LDL-C) and lowering coronary heart disease risk.
      However, many patients receiving statin therapy in clinical practice are not
      achieving their LDL-C goals. Generally, statins are initiated at starting doses,
      and doses should be titrated as needed until the goal of therapy is achieved or a
      second lipid-lowering drug is required; titration is required in the majority of
      patients who receive less efficacious agents. Most patients receiving statin
      therapy in clinical practice are maintained on their starting dose, and this
      frequently results in inadequate control of elevated cholesterol levels. A number
      of factors may limit dose titration in clinical practice, including the cost of
      therapy, safety of prescribing statins at high doses and the additional office
      visits required for evaluations and monitoring. There may be several solutions to
      this problem. The choice of statin appears to be one of the important factors
      influencing the success of therapy. Selecting a statin that provides greater LDL
      C lowering enables more patients to achieve LDL-C goals, and the majority of
      patients can be effectively treated with starting doses of the more efficacious
      statins. Another factor influencing the success of therapy is the willingness to
      add other drugs to a statin to enhance LDL-C lowering. Choices here include
      niacin, a bile acid sequestrant, and ezetimibe, a new cholesterol absorption
      inhibitor. Of these approaches, use of a more efficacious statin is preferred to
      combination therapy because of cost, safety, effectiveness, and simplicity
      issues.

PMID- 14704597
TI  - The emerging role of bisphosphonates in prostate cancer.
AB  - Bisphosphonates are a class of therapeutic agents originally designed to treat
      loss of bone density. It has been shown that the primary mechanism of action is
      inhibition of osteoclastic activity. Accumulating data show that these drugs are
      useful in diseases with propensities toward osseous metastases. In particular,
      they are effective in diseases in which there is clear upregulation of
      osteoclastic or osteolytic activity such as breast cancer and multiple myeloma.
      Despite the fact that osseous metastases in prostate cancer manifest as
      osteosclerosis rather than osteolysis, studies now show that bisphosphonates are
      useful in the management of this disease. In particular, they have demonstrated
      an impact on osteoporosis associated with hormonal therapy, bone pain from
      metastases, and skeleton-related events from prostatic adenocarcinoma. This
      review briefly summarizes the available clinical data on the utilization of
      bisphosphonates in the disease of prostate cancer.

PMID- 14704598
TI  - A case of herceptin cardiotoxicity.

PMID- 14704599
TI  - Ciprofloxacin- and hypocalcemia-induced torsade de pointes triggered by
      hemodialysis.
AB  - Torsade de pointes is a polymorphic form of ventricular tachycardia associated
      with prolongation of the QT interval, which may be either congenital or acquired.
      Etiologies for the acquired forms include drug effects, hypokalemia,
      hypomagnesemia, hypocalcemia, starvation, sick sinus syndrome, and
      atrioventricular block. We present a 76-year-old man with acute on chronic renal
      failure, hypocalcemia, on ciprofloxacin, and a prolonged QT interval with torsade
      de pointes triggered by hemodialysis. The QT prolongation was corrected by
      treating the hypocalcemia. Hypocalcemia and ciprofloxacin are known to
      independently cause prolonged QT interval and torsade de pointes; our case
      illustrates that dialysis can trigger torsade on a background of this risk factor
      combination.

PMID- 14704601
TI  - Recipe for change. Transforming your New Year's resolutions into healthy behavior
      change.

PMID- 14704602
TI  - Arthritis medication studied for Alzheimer's disease prevention.

PMID- 14704603
TI  - Experimental vaccine may curb recurrent urinary tract infections.

PMID- 14704604
TI  - Getting to the root of healthy teeth.

PMID- 14704606
TI  - The placebo effect. Harnessing your mind's power to heal.

PMID- 14704605
TI  - Celiac disease. An intolerance to gluten.

PMID- 14704607
TI  - One on one. Taking statins.

PMID- 14704610
TI  - Mayo Clinic office visit. Diabetes. An interview with Robert Rizza, M.D.

PMID- 14704611
TI  - Association between psychological disorders and the presence of Oral lichen
      planus, Burning mouth syndrome and Recurrent aphthous stomatitis.
AB  - OBJECTIVE: The aim of this study was to determine the existing relation between
      the Oral Lichen Planus (OLP), Recurrent Aphthous Stomatitis (RAS), Burning Mouth
      Syndrome (BMS) and psychological alterations of the patient, such as stress,
      anxiety and depression. DESIGN OF THE STUDY: 18 patients with RAS, 9 patients
      with OLP and 7 patients with BMS, that presented the condition at the moment of
      the examination, were studied, as well as a control group of 20 healthy patients.
      Both groups were extracted of hospitals and university centers, where the
      clinical diagnosis was made by a team of oral pathologists. Two measuring
      instruments were applied to them about their psychological condition: the Test of
      Recent Experience, to measure the stress level and scale H.A.D., to determine the
      level of anxiety and depression; the score given by them were statistically
      analyzed through T-test and the ANOVA Tukey test. RESULTS: Our results suggested
      a statistically significant association between these psychological disorders and
      the diseases of the oral mucosa in study. It was observed that the stress level
      is greater in patients with RAS and OLP, depression is particularly high in
      patients with BMS, and levels of anxiety are raised in the three groups, in
      comparison with the group control. CONCLUSIONS: A positive relationship can be
      established between psychological alterations and RAS, OLP and BMS. The RAS and
      the OLP stress and anxiety levels were considered as high, whereas the BMS was
      more related to important levels of anxiety and depression. According to these
      findings it is possible to assume that psychological factors should be taking
      into account when oral health wants to be maintain as normal.

PMID- 14704612
TI  - Burning Mouth Syndrome: open trial of psychotherapy alone, medication with alpha
      lipoic acid (thioctic acid), and combination therapy.
AB  - OBJECTIVE AND STUDY DESIGN: This open study of 192 otherwise healthy persons with
      burning mouth syndrome, examined the efficacy on control of symptoms of
      psychotherapy alone with two hour sessions weekly for two months; alpha lipoic
      acid (ALA, tioctic acid; Tiobec) 600 mg/day alone for two months; or combination
      therapy of psychoanalysis and 600 mg/day ALA for two months. Controls received
      placebo alone. RESULTS: Most benefit was obtained with combination therapy.
      Combination therapy of psychoanalysis and alpha lipoic acid (ALA, tioctic acid;
      Tiobec. 600 mg/day) for two months gave most benefit and significantly more than
      psychoanalysis alone for two 1 hour sessions weekly for two months (p<0.0005), or
      ALA 600 mg/day alone for two months (p<0.0005). CONCLUSION: The present results
      suggest that alpha lipoic acid may complement psychotherapy and can be an
      acceptable alternative to psychoactive agents, but trials to compare the two
      approaches are now warranted.

PMID- 14704613
TI  - Effects of the consumption of alcohol in the oral cavity: relationship with oral
      cancer.
AB  - In an epidemiologic point of view the consumption of alcoholic beverages is found
      to be associated to an increased risk for developing an upper gastrointestinal
      tract cancer. The relation of the studies that establish this connection is
      complicated due to both the confluence of various risk factors within the same
      person such as alcohol and tobacco, and to the lack of data that can be
      verifiable by the clinician. For this reason the exact pathogenic mechanism
      responsible for this increase of risk is not known since ethanol per se was not
      confirmed to be carcinogenic. Different hypotheses have been proposed, explaining
      how ethanol, by oral or systemic route, can act as a risk factor for the
      development of oral cancer. This article serves as a review of the actual
      situation of the potential pathogenic mechanisms, dividing them in local and
      systemic effects. Within the aforementioned special reference is made on the
      alteration of the oral mucosa permeability, the action of acetaldehyde and the
      role of retinoids.

PMID- 14704614
TI  - Alcoholic parotid sialosis: a structural and ultrastructural study.
AB  - OBJECTIVES: The purpose of this study is to demonstrate the histopathological
      differences between the initial and advanced stages of Alcoholic Sialosis, a
      pathology that generally involves parotid hypertrophy and structurally affects,
      to diverse degrees, the other salivary glands. STUDY DESIGN: An analysis and
      comparison was carried out of the structural and ultrastructural modifications of
      the parotid glands from the hepatic biopsies of chronic alcoholics with clinical
      diagnosis of cirrhosis and from autopsies on individuals who had died from
      alcoholic hepatic cirrhosis. Various samples of normal gland obtained from
      surgical material were used as a control. RESULTS: The alterations found in the
      biopsies corresponded to the modifications discovered in the autopsies of
      alcoholics. Notable in both cases was the massive accumulation of secretory
      granules of different size, shape and electrodensity, which occupied the
      cytoplasm of the acinar cells. In both sample types the excretory ducts were
      enlarged and the epithelium of the striate ducts presented cells with nuclei and
      cytoplasm of irregular appearance and arrangement. A moderate adipose
      infiltration in the stroma and slight periacinal edema was also observed. The
      biopsies revealed, both at optical and electron microscopical levels, lipid
      inclusions in the acinar cells and the glandular parenchymal ducts. CONCLUSIONS:
      The structural and ultrastructural findings of the parotid biopsies and
      autopsies, clearly show that alterations are already present in the salivary
      glands of chronic alcoholics before the terminal phase of hepatic cirrhosis. The
      enlargement of the ductal system lumens could be the principal cause of glandular
      hypertrophy.

PMID- 14704615
TI  - Secondary syphilis in an HIV positive patient.
AB  - The incidence of oral manifestations of HIV infection is changing markedly. Oral
      afflictions previously uncommon in HIV condition are now emerging in this
      scenario and may be underestimated. Clinical characteristics of some oral
      diseases could change in the presence of HIV/AIDS infection and health care
      professionals must be made aware of such changes. Oral lesions of secondary
      syphilis are rare, however they can occur and the dentist should be able to
      diagnose them. In some cases the anamnesis and the clinical features of the
      lesions are not enough to diagnose this disease. Histological features and an
      acute knowledge on laboratory exams, as well as its applicability and limitations
      are necessary to diagnose it. The present report describes a case of secondary
      syphilis in an HIV positive patient. The patient showed red spots in the torso of
      skin and abdomen. The spots were also present on the hands but the color was
      darker. The oral mucosa had several ulcers, with variable shapes, sometimes
      recovered by a white and resistant membrane. They were present in the buccal
      mucosa, palate, gingiva, tongue and labial mucosa. Those clinical manifestations
      appeared 6 months earlier. Exams were performed (VDRL, FTA-abs, direct fungal
      exams in the skin and oral mucosa and a biopsy in the oral mucosa) but the
      diagnose remained unclear. Clinical and laboratory features disagreed and
      postponed the final diagnosis and the treatment for more than 6 months.

PMID- 14704616
TI  - Oral manifestations caused by the linear IgA disease.
AB  - The Linear IgA deposit related disease or Linear IgA disease (LAD) is a chronic,
      uncommon and autoimmunological mucocutaneous disease, characterised by linear IgA
      deposits along the basement membrane zone. In mainly cases, moreover cutaneous
      lesions, there are oral mucosal and other mucosal lesions. There are also, some
      cases published of Linear IgA disease limited to oral mucosa. The known of this
      disease is important for the establishment of a correct differential diagnosis in
      cases of blistering mucocutaneous diseases. In this paper, we analyze the most
      important features of this disease, attending specially to the oral
      manifestations.

PMID- 14704617
TI  - Sedation in the geriatric patient.
AB  - A review is made of the utility of iatrosedation and pharmacological sedation in
      the dental treatment of elderly patients. The adoption of such measures is
      required due to the increased prevalence of oral pathology, poorer stress
      tolerance and frequent association of systemic disease in such patients. A
      description is made of the recommended psychoactive drug administration routes
      according to the associated pathology and of the most frequent pharmacological
      interactions with the background disease. Drug sedation should always be
      accompanied by psychological measures to minimize the required drug dose, and by
      correct locoregional anesthesia.

PMID- 14704618
TI  - Chemoprophylaxis of bacterial endocarditis recommended by general dental
      practitioners in Spain.
AB  - The aim of this study was to assess the current practice of antibiotic
      prophylaxis of Bacterial Endocarditis (BE) among General Dental Practitioners
      (GDPs) in Spain. GDPs were asked over the telephone by a fictitious patient what
      antibiotic prophylaxis they would administer to an "at risk" patient for BE
      before a tooth extraction. Four hundred randomly selected Spanish GDPs were
      surveyed, 200 of them were asked about BE prophylaxis in penicillin non-allergic
      patients and the remaining 200 in penicillin allergic patients. Of the GDPs
      surveyed, 182 (45.5%) did not recommend any prophylactic treatment; 74.7% of
      those stated that an oral examination before treatment was needed and 25.3%
      referred the patient to his/her physician or cardiologist for further advice. Of
      the 97 GDPs who recommended antibiotics to penicillin nonallergic patients, only
      30 (30.9%) suggested the prophylactic guidelines proposed by the American Heart
      Association or the British Society for Antimicrobial Chemotherapy. For penicillin
      allergic patients, 68.2% of the GDPs prescribed erythromycin as the antibiotic of
      first choice, while 17.6% of the GDPs prescribed clindamycin. Nonetheless, fewer
      than 30% administered both antibiotics with the adequate dosages. These results
      show important gaps in the knowledge of antibiotic prophylaxis for "at risk"
      patients before dental procedures among Spanish GDPs.

PMID- 14704619
TI  - Intraosseous intraneural perineurioma: report of a case with morphological,
      immunohistochemical and FISH study.
AB  - We report a case of an intramandibular intraneural perineurioma developed in the
      left dentary nerve. This tumour is rare and shows a typical histological,
      immunohistochemical and ultrastructural appearance: concentric whorls of
      perineurial cells EMA+ and PS100- around nerve fibers. This tumour must be
      distinguished from extraneural or soft tissue perineurioma, also composed of
      perineurial cells, with distinct clinical presentation and histological
      appearance, and from localized hypertrophic neuropathy, a reactive process
      frequently identified with intraneural perineurioma. Cytogenetic evidence for the
      neoplastic nature of this tumour is also presented in this report.

PMID- 14704620
TI  - Cemento-ossifying mandibular fibroma: a presentation of two cases and review of
      the literature.
AB  - We present two clinical cases of radiolucent mandibular lesions in young women
      that simulated chronic periapical infectious pathology. The detection of both
      cases was fortuitous since they were totally asymptomatic. Diagnosis was reached
      in one case (upon periapical surgery and anatomo-pathologic study) after
      endodontic treatment and after verifying non-resolution of affected periapical
      area. The other case was an extensive lesion, which involved the periapices of
      the four inferior incisors in which surgery was directly performed upon verifying
      pulp vitality of these teeth. After surgery endodontic treatment was performed on
      the teeth that had lost their vitality. In both cases the histopathologic tests
      revealed the presence of a cemento-ossifying fibroma, the initial clinical and
      radiographic diagnosis of which could easily be overlooked.

PMID- 14704621
TI  - Update on immediate implant loading: a review of the literature.
AB  - The treatment of totally or partially edentulous patients with osseointegrated
      implants is an increasing part of daily dental practice. The greater aesthetic
      and functional demands made by these patients have created a constant pressure to
      reduce the waiting time before implants are loaded. In some cases, however, a
      shortening of the waiting period may compromise the osseointegration of the
      fixtures. The present review aims to inform the clinician about the continuing
      controversy on this issue. Data from the reviewed studies allow comparisons to be
      made between the different success rates obtained after immediate implant
      loading, offering a more objective basis for our advice to patients on this type
      of treatment. According to our review, the type and quality of the bone and the
      surface of the implant are the factors that determine the selection of patients
      who can undergo the premature loading of implants.

PMID- 14704622
TI  - Solitary fibrous tumor of the parotid region. Report of a case and review of the
      literature.
AB  - Solitary fibrous tumor is a well-recognized entity that most commonly involves
      the pleura; however, it has been recently described in other locations including
      the head and neck region, where it occurs as a slowly growing and well
      circumscribed lesion. Due to its low frequency it may be confused with other
      neoplasms, and for this reason microscopic, ultrastructural and
      immunohistochemical features are necessary to establish its diagnosis. Prognosis
      of this tumor depends on its location and size. We present a 20-year-old woman
      with a well circumscribed, rapidly enlarging solitary fibrous tumor located in
      the parotid region, which protruded into the oral cavity, measured 10 x 8.5 x 5.5
      cm and exhibited benign histological features and positive immunoreactivity to
      CD34.

PMID- 14704623
TI  - [Differential diagnosis of submandibular swellings and tumors].

PMID- 14704624
TI  - [B cell lymphoma].

PMID- 14704625
TI  - [Pemphigus vulgaris].

PMID- 14704626
TI  - A new computed-assisted technique for experimental sciatic nerve function
      analysis.
AB  - BACKGROUND: Peripheral nerve injury is a well-known experimental tool to evaluate
      the effect of various neurotrophic substances. Besides histological and
      electrophysiological techniques, nerve functional status has been assessed by
      means of the sciatic function index (SFI) and the static sciatic index (SSI).
      However, these techniques are still based on a complex and old-fashioned
      apparatus requiring a relatively long time of execution. This study aimed to
      assess a novel, rapid, computerized method for assessment of SSI in a rat model
      of sciatic nerve injury. MATERIAL/METHODS: Fourteen rats were used in this study.
      The left sciatic nerve was exposed and compressed for 2 minutes with an aneurysm
      clip. Functional evaluation was performed by analysing the footprints of standing
      rats, comparing the injured to the uninjured limb with the static sciatic index
      (SSI). For this purpose the rats were placed on a digital scanner and the
      resulting images were acquired on a personal computer. Analysis was carried out
      every day after surgery for 21 consecutive days. RESULTS: Two-minute compression
      of the sciatic nerve produced a major reduction in motor function as assessed by
      SSI. Improvement was observed by day 7. By day 20, SSI was completely restored.
      CONCLUSIONS: This technique is simple to use, quick, without expensive technical
      equipment. It provides good accuracy and precise quantification of the extent of
      functional loss and recovery after sciatic nerve injury.

PMID- 14704627
TI  - Protease inhibitor leupeptin attenuates myocardial stunning in rat heart.
AB  - BACKGROUND: In order to test the hypothesis that cardiac protein degradation
      contributes to the pathogenesis of myocardial stunning, the effect of protease
      inhibitor leupeptin on the postischemic hemodynamics and metabolic functioning
      was measured in isolated rat hearts. MATERIAL/METHODS: Isolated rat hearts were
      perfused in Langendorff mode in the presence or absence of leupeptin (10 Kg/ml
      for 10 min.), and then subjected to 20 min. of normothermic ischemia and 30 min.
      of reperfusion. Aortic pressure, cardiac output, coronary flow (CF), global
      oxygen consumption (MVO2), carbon dioxide and [H+] release, and [Ca2+] uptake
      were investigated. RESULTS: Hearts pretreated with leupeptin exhibited better
      postischemic return of systolic, diastolic and developed aortic pressure and
      faster return of CF to preischemic values during reperfusion. MVO2 and CO2
      release were lower in this group in the 10th and 15th min. of reperfusion and
      [Ca2+] uptake higher in the 5th and 15th min. of reperfusion CONCLUSIONS:
      Leupeptin protects the heart from myocardial stunning, which is consistent with
      the idea that proteases contribute to the pathogenesis of this phenomenon.

PMID- 14704628
TI  - The influence of glimepiride on the binding kinetics of insulin with its skeletal
      muscle and liver receptors in rats with short term and prolonged hyperglycemia
      induced by streptozotocin.
AB  - BACKGROUND: The aim of the study was to determine the influence of glimepiride on
      the binding kinetics of insulin with its skeletal muscle receptor in rats with
      transient and prolonged hyperglycemia induced by streptozotocin.
      MATERIAL/METHODS: The studies were performed on healthy male Wistar rats with a
      body mass of 220+/-30 g, fed with LSM-type standard chow, and given water ad
      libitum. Transient or prolonged hyperglycemia was induced by intraperitoneal
      administration of streptozotocin. Blood samples were taken from the right heart
      ventricle to heparinized test tubes and centrifuged for 10 minutes at 700 i. g.
      Plasma was collected and the glucose level was determined. From each animal 1 g
      of skeletal muscle and 1 g of liver were collected as well, placed in liquid
      nitrogen and stored until determination of the affinity and number of receptors.
      RESULTS: We found an increase in affinity and binding capacity of high- and low
      affinity receptors in rats with both transient and prolonged streptozotocin
      induced hyperglycemia. The affinity and binding capacity of receptors increased
      under the influence of glimepiride in transient hyperglycemia caused by
      streptozotocin administration. CONCLUSIONS: The affinity and binding capacity of
      receptors increased under the influence of glimepiride in the course of transient
      hyperglycemia. The lack of changes in the specific insulin binding and binding
      capacity of receptors of both low and high affinity in the group of animals with
      prolonged hyperglycemia requires explanation.

PMID- 14704629
TI  - Comparison of two media for sequential culture after IVF and ICSI shows no
      differences in pregnancy rates: a randomized trial.
AB  - BACKGROUND: Optimal culture conditions are crucial for embryonic development and
      blastocyst formation after in vitro fertilization (IVF) or Intracytoplasmic sperm
      injection (ICSI). A prospective randomized trial was carried out to compare the
      effects of two different sequential media (Vitrolife and MediCult) on embryo
      development and implantation. MATERIAL/METHODS: 176 couples were included in this
      prospective randomized study. All couples undergoing the IVF (n=84) or ICSI
      (n=92) program at the University of Wurzburg were randomly assigned to either
      Vitrolife (n=87) or MediCult (n=89) sequential culture media. RESULTS: The
      overall median fertilization rate (FR) was 84.0% and was similar in the Vitrolife
      (FR=87.5%) and MediCult group (FR=80.0%). A mean of 2.7 embryos were replaced
      into the uterus, not significantly different between both groups. The pronuclear
      development was significantly enhanced in embryos cultured in Vitrolife than in
      those cultured in MediCult media (p=0.035). The embryonic development on day 3
      was also superior in the Vitrolife group, but only in ICSI cycles (p<0.01). After
      5 days of culturing, the blastocyst development was equivalent in both groups.
      The clinical pregnancy rate was 31.0% per transfer in the Vitrolife group and
      28.1% in the MediCult group (not significant). CONCLUSIONS: The results
      demonstrate that implantation and clinical pregnancy rates with both media are
      comparable. Embryonic development until day three seemed to be enhanced when the
      embryos were cultured in Vitrolife media.

PMID- 14704630
TI  - Neuropsychological follow-up into young adulthood of term infants born small for
      gestational age.
AB  - BACKGROUND: The aim of the study was to investigate whether children born small
      for gestational age without other complications nor signs of neurological
      impairment or developmental delay before 18 months of age may display
      neuropsychological impairments later in life. MATERIAL/METHODS:
      Neuropsychological outcome, school achievement, and social adjustment in young
      adulthood (21-28 years of age) were investigated in a prospectively followed
      group of 17 children born small for gestational age (SGA) and compared with 30
      controls born with appropriate weight. A questionnaire including items about
      highest education, present social situation, and self-estimation of health was
      conducted. A comprehensive neuropsychological assessment of the main aspects of
      cognitive function was performed in 12 young adults from the SGA group and
      compared with 18 subjects selected as normal controls. Intelligence, verbal
      functions, visuo-spatial and visuo-constructive functions, learning and memory of
      words and figures, attention, lateral preference, motor functions, and cognitive
      adaptive functions were investigated. RESULTS: The young adults born SGA
      displayed lower intelligence quotients, specifically reduced verbal comprehension
      and deficits in figurative learning and memory functions, compared with normal
      controls. No differences in educational achievement and social adjustment were
      found. Neither were any differences observed in maternal education levels.
      CONCLUSIONS: Infants born SGA display a reduced cognitive capacity at young adult
      age compared with controls. However, this lower capacity is not considered
      sufficiently severe to affect educational level or social adjustment.

PMID- 14704631
TI  - Alcohol involvement in burn, submersion, spinal cord, and brain injuries.
AB  - BACKGROUND: Alcohol is involved in many injuries, but estimates of this
      involvement vary considerably. Most information pertains to deaths although most
      injuries are nonfatal. MATERIAL/METHODS: The portion of fatal and nonfatal
      injuries involving alcohol was determined from a comprehensive Oklahoma
      surveillance system that tracks persons killed or hospitalized due to burns,
      submersions, spinal cord injuries (SCIs), and traumatic brain injuries (TBIs).
      Logistic regression was used to determine factors that explain the percentage of
      alcohol involvement in fatal versus nonfatal cases. RESULTS: The victim was
      alcohol involved in 17% of fire burns, 4% of scald burns, 24% of submersions, 34%
      of SCIs, and 41% of TBIs where involvement was known. Large differences existed
      in total alcohol involvement between age and gender groups and between fatal and
      nonfatal cases of fire burns (31% vs.11%) and submersions (33% vs. 6%). Large
      differences also existed in victim alcohol involvement between fatal and nonfatal
      cases of intentional SCIs (0% vs. 48%) and TBIs (38% vs. 70%). Those who imbibed
      during the day were not at excess risk of scald injury, but they were twice as
      likely to suffer a serious fire burn, 3 times as likely to suffer a spinal cord
      injury, 3.5 times as likely to suffer a submersion injury, and 2 to 4 times as
      likely to suffer a TBI. These excess risks persisted for all age groups between
      15 and 64, with the excess risk especially high for underage drinkers aged 15 to
      20. In contrast, people aged 65 and older did not appear to be at excess risk on
      days that they imbibed. CONCLUSIONS: A large percentage of fatal and nonfatal
      injuries as classified by diagnosis group involve alcohol. People who had been
      drinking were substantially more likely to suffer serious nonfatal and fatal
      injuries other than scald burns.

PMID- 14704632
TI  - Relationship of intercellular adhesion molecule-3 and hepatocyte growth factor
      with amyloidosis A in chronic renal-failure patients.
AB  - BACKGROUND: Patients with chronic renal failure have elevated serum levels of
      intercellular adhesion molecules and hepatocyte growth factor. The aim of this
      study was to investigate immunohistochemically whether these substances are
      associated with amyloidosis A in this patient group. MATERIAL/METHODS: Liver
      needle-biopsy specimens from 40 chronic renal-failure patients, 20 with
      amyloidosis A (Group I) and 20 without this disease (Group II), were
      investigated. Twenty control liver biopsies were obtained from healthy
      individuals (Group III). All specimens were immunohistochemically stained to
      determine the presence and density of hepatocyte growth factor and intercellular
      adhesion molecule-3. RESULTS: The levels of positivity for hepatocyte growth
      factor and intercellular adhesion molecule-3 in Groups I and II were
      significantly higher than the levels in the control group. Also, the Group I
      sections had significantly more cells that were positive for intercellular
      adhesion molecule-3 than the Group II sections (p<0.016). There was no
      significant difference between Groups I and II regarding the level of positivity
      for hepatocyte growth factor. CONCLUSIONS: The fact that there was a higher
      density of intercellular adhesion molecule-3-positive cells in the patients with
      amyloidosis A indicates that this substance may be a microenvironmental factor in
      this disease. If this is true, regulating the serum level of this molecule may
      prevent amyloid A in chronic renal-failure patients.

PMID- 14704633
TI  - The influence of two different doses of L-arginine oral supplementation on nitric
      oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic
      patients.
AB  - BACKGROUND: The purpose of this study was to assess the effect of two different
      doses in 28-day L-arginine oral supplementation on nitric oxide (NO)
      concentration and total antioxidant status (TAS) in patients with atherosclerotic
      peripheral arterial disease at Fontaine's stages II and III. MATERIAL/METHODS: 32
      patients were divided into 2 groups receiving L-arginine at 3i2 g/day (group A)
      or 3i4 g/day (group B). Nitric oxide concentration was determined with the
      testing set provided by Oxis using a Hyperion Micro Reader. Total antioxidant
      status (TAS) in mmol/l was established in serum with the RANDOX NX2332 test.
      RESULTS: Group A showed substantially higher NO levels after 14 and 28 days of
      therapy. In group B, the NO level increase was substantial after 28 days.
      Noticeably higher total antioxidant statuses were noted in both groups: group A
      showed this only after 28 days of treatment, while group B exhibited substantial
      increase in TAS after 7, 14 and 28 days of L-arginine supplementation.
      CONCLUSIONS: Oral supplementation of L-arginine for 28 days leads to substantial
      increases in NO and TAS levels (comparable in both groups of patients) in the
      blood of patients with atherosclerotic peripheral arterial disease at Fontaine's
      stages II and III. The TAS concentration rise points to an antioxidative effect
      of L-arginine oral supplementation.

PMID- 14704634
TI  - Expression of TGF beta1 genes and their receptor types I, II, and III in low- and
      high-grade malignancy non-Hodgkin's lymphomas.
AB  - BACKGROUND: Transforming growth factor beta (TGF ) is involved in a variety of
      important cellular functions. The lack of TGF -dependent cell-growth control
      might be related to oncogenesis, as it has been shown in lung, breast, and colon
      carcinomas. Current observations have revealed that TGF  is rather an inhibiting,
      not a stimulating, factor as far as malignant tumor development is concerned.
      Recently, however, there has been a growing number of reports on increased
      expression of TGF  genes in certain tumors. In patients with a diagnosis of non
      small-cell lung carcinoma, the tumors expressing high levels of TGF  were the
      ones that had a higher proliferation and metastasis capability, whereas more
      promising were the cases with lower levels of TGF  expression. MATERIAL/METHODS:
      A pilot study of 14 patients was conducted comprising 8 patients with a low-grade
      lymphoma and 6 patients with a high-grade lymphoma. The QRT-PCR method was
      employed to assess the activity of TGF 1 and of its receptor types I, II, and
      III. RESULTS: The expression values for TGF 1 and its receptors I, II, and III
      were twice as high in the group of patients with a diagnosis of high-grade
      lymphomas as in the group of patients diagnosed with low-grade lymphomas.
      CONCLUSIONS: Results showed a clear difference in TGF 1 expression in patients
      with NHL depending on the subtype of the lymphoma, suggesting its significant
      role in the pathomechanism of this group of malignant diseases as well as its
      potential value as a prognostic factor.

PMID- 14704635
TI  - Lymphocytic gastritis in pediatric celiac disease -- immunohistochemical study of
      the intraepithelial lymphocytic component.
AB  - BACKGROUND: Lymphocytic gastritis (LG) is defined by the recognition of >25
      intraepithelial lymphocytes (IEL) per 100 surface epithelial cells. Approximately
      50% of children with celiac disease (CD) present LG, which mainly involves the
      gastric antrum and disappears after a gluten-free diet. This intraepithelial
      population of lymphocytes has not been immunophenotypically characterized for
      this age group. MATERIAL/METHODS: We immunohistochemically analyzed 5 formalin
      fixed, paraffin embedded biopsies of LG in children with untreated celiac disease
      using a panel of antibodies. All patients were diagnosed on the bases of
      clinical, laboratory and histopathological data. RESULTS: All showed similar
      results. IEL proved to be CD45RO, CD3, CD7, CD8, and Tia-1 positive, while CD4,
      CD20, CD79a, CD56, CD57, granzyme B, perforin, TCR gamma-delta, TCR beta (V-19),
      CD95 (FAS), CD95-L (FAS-L) and HLA II were negative. Many IEL were in apoptosis.
      CD45RO, CD3 and CD7 presented as membranous staining, while Tia-1 resulted in
      intracytoplasmic granular brown dots. In 3 cases there were rare lymphocytes with
      granzyme B-positive granules localized to the lamina propria. None presented
      Helicobacter pylori -like organisms at the luminal surface. CONCLUSIONS: LG
      associated with CD in children contains a peculiar CD8+ intraepithelial T
      lymphocyte population which immunohistochemically lacks perforin and granzyme B,
      undergoes apoptosis, and is not associated with substantial damage to the
      epithelial cells. Our results fit with those reported in adults except for the
      negative results for granzyme B. The findings appear disparate from the ones
      described in the duodeno-jejunal mucosa in untreated celiac disease.

PMID- 14704636
TI  - Fracture of the clavicle after surgical treatment for congenital pseudarthrosis.
AB  - BACKGROUND: Congenital pseudarthrosis of the clavicle is a rare disease. There
      are about 200 individual cases reported so far in world literature, mainly in the
      form of case reports. The majority of authors recommend surgical. An analysis of
      103 cases published since 1980 shows only a few post-surgical complications. CASE
      REPORT: The authors present a female patient operated at the age of 4.5 years.
      During surgery both cartilaginous ends were resected and internal fixation was
      performed by a one-third semitubular plate fixed by 3.5 mm cortical screws. Ten
      days after hardware removal, a fracture occurred in the screw-hole following a
      minor impact. Surgery to heal the congenital pseudarthrosis was successful, but a
      new fracture occurred, resulting from bone weakening. This simple fracture was
      treated conservatively. At present (5 years after the first surgery) the
      patient's parents are completely satisfied with both the functional result and
      the cosmetic appearance. CONCLUSIONS: The authors have not found in the
      literature any reports of similar complications after surgical treatment of this
      condition. The use of more delicate osteosynthetic material might prevent the
      complication described here.

PMID- 14704638
TI  - Open access publishing -- panacea or Trojan horse?
AB  - There has been a great deal of press material and discussion in recent years
      regarding open access for online professional publishing. The issue has divided
      publishers, authors and readers, leaving almost no one neutral. This new concept
      can potentially affect the majority of publishing businesses, creating new
      leaders and destroying old ones. It may also, if accepted, radically change the
      ways we use to store, deliver, and retrieve information. The article presents
      critical view on the current situation in scientific publishing business
      indicating constantly rising subscription costs as one of the triggers for a
      change. The authors analyze the 'open access publishing' idea, pointing out the
      myths and slogans used by its supporters. The criticism has been expressed on a
      high costs of publishing shifted on to researchers. The authors propose their
      solution based on lower submission fees and micro-payments for article access,
      which might be acceptable to all interested: authors, readers and publishers.

PMID- 14704637
TI  - Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis C.
AB  - BACKGROUND: Recombinant interferon-alpha (IFN-alpha ) is widely used for the
      treatment of chronic hepatitis C. Pulmonary side effects of IFN-alpha therapy
      seem to be rare. So far, only a few cases of sarcoidosis in association with IFN
      alpha treatment of chronic hepatitis C have been CASE REPORT: A 52-year-old woman
      with chronic hepatitis C developed sarcoidosis during treatment with IFN-alpha.
      Diagnosis of sarcoidosis was based on chest imaging studies, the increased serum
      angiotensin converting enzyme levels, and the histology of a biopsied cervical
      lymph node. Spontaneous remission was observed following IFN-alpha withdrawal.
      CONCLUSIONS: Use of recombinant IFN-alpha in patients with chronic hepatitis C
      may trigger or contribute to the development of sarcoidosis in susceptible
      individuals. Patients should be monitored during and following IFN-alpha therapy
      for the occurrence of manifestations suggesting sarcoidosis.

PMID- 14704639
TI  - Aneurysm: prevention and nonsurgical repair.
AB  - The approximately 4000 'normal' mammals that synthesize ascorbic acid produce on
      average circa 50 mg/kg per day routinely. Although humans have the same needs as
      normal mammals, they do not produce ascorbic acid at all and, on average, ingest
      only circa 1 mg/kg per day. The normal mammals' much larger production enables
      them to continually renew structural proteins, including both collagen, a
      flexible but inelastic tissue, and elastin, the elastic connective tissue. As a
      result, many normal mammals maintain a 'youthful' appearance with little gross
      anatomical change from age of maturity (i.e, first estrus) to more than 20 times
      age of maturity. In stark contrast, the extremely small ascorbic acid intake of
      humans does not enable them to maintain a youthful flexibility and elasticity
      beyond possibly 6 times age of maturity (most have died before 8 times). This
      loss of youthful qualities in structural proteins results in susceptibility for
      many forms of deterioration in both appearance and properties of vascular and
      other structural tissues. One such deterioration is aortic aneurysm, a common
      cause of morbidity and mortality. We hypothesize herein that improved dietary
      intake of essential nutrients needed to enhance the renewal of all structural
      proteins can: (1). prevent this deterioration completely; and (2). cure even
      large aortic aneurysms without surgery.

PMID- 14704640
TI  - Diagnosis of symptomatic kala-azar by polymerase chain reaction using patient's
      blood.
AB  - BACKGROUND: Detection of Leishmania parasite in patients by classical methods at
      the early stage of infection is limited. Several studies have shown that
      polymerase chain reaction (PCR) is more effective for the diagnosis of visceral
      Leishmaniasis (VL) in clinical samples. The purpose of this study was to develop
      a simple, specific and sensitive PCR-based assay for detecting VL caused by any
      species of the genus Leishmania. MATERIAL/METHODS: We examined blood samples from
      twenty suspected kala-azar patients by polymerase chain reaction (PCR) using
      Leishmania specific primers. The results of the PCR-based procedure were compared
      with those of the Leishman-Donovan (LD) body test, immunodiffusion assay (IDA),
      and direct agglutination test (DAT). RESULTS: Out of the twenty samples, only
      five were found to be positive using all four tests. However, twelve samples were
      positive using the PCR assay, and among these only ten samples were found to be
      positive by LD body test of bone marrow smears. The results clearly indicated
      that, unlike the LD body test routinely used for diagnosis of kala-azar, the PCR
      assay is 100% sensitive. CONCLUSIONS: This method is very useful for primary
      screening of blood samples of patients suffering from kala-azar-like symptoms,
      especially in endemic areas.

PMID- 14704641
TI  - Suppression of power-line interference by analog notch filtering in the ECG
      signal for heart rate variability analysis: to do or not to do?
AB  - BACKGROUND: Heart rate variability analysis has developed recently to a promising
      field of cardiology. Measures of heart rate variability can be corrupted by
      environmental noise or technical artifacts arising from analog and digital signal
      processing. MATERIAL/METHODS: The present investigation addressed the analysis of
      the effects of AC interference and its filtering on the precision and accuracy of
      heart rate detection. Artificial ECG recordings with predefined parameters were
      simulated by a computer and a data acquisition card, consecutively filtered by an
      analog notch filter (Q=2, 5 and 10) and digitized at 1 kHz by the same card ahead
      of and subsequent to the filter circuit. These latter signals were analyzed: the
      relative time points corresponding to the uncorrupted series at 7 points of the
      ventricular complexes were obtained and their means, standard deviations and
      maxima were computed separately. RESULTS: The filtering of uncorrupted ECG
      signals does not result in heart rate period deviations < or=1 ms. Power-line
      interference contamination proportionally alters the accuracy of representative
      point detection (maximal shift: 5% - 2 ms, 10% - 4 ms, 25% - 8 ms, 50% - 14 ms),
      which is consistently restored by notch filtering with a slight error (L1 ms on
      the ascending slope and at the peak). The descending slope is more distorted at
      filter Q=2 and at lower ventricular complex width; however this is constant,
      which also results in reliable RR-interval detection. CONCLUSIONS: AC notch
      filtering of ECG signals for heart rate variability analysis is considered
      important, and further investigation of this area is encouraged.

PMID- 14704642
TI  - Fractal analysis of tracheal sounds during maximal forced exhalation.
AB  - BACKGROUND: Fractal structures or processes, many of which are found in nature,
      are marked by the presence of a formal pattern that repeats itself even as the
      scale changes, a property termed 'self-similarity'. The bronchial tree is
      structurally a fractal system and inspiration is a fractal process. Our objective
      was to show that the dynamic process of emptying air from the bronchi as measured
      by tracheal sounds should also behave fractally over the period of time during
      which exhalation takes place. MATERIAL/METHODS: Twenty non-smoking patients (9
      males and 11 females) aged 53.6+/-16.3 years with persistent but clinically
      stable moderate to severe asthma and a control group of 11 healthy non-smoking
      subjects (6 males and 5 females) aged 46.0+/-12.5 years were enrolled.
      Respiratory sounds were registered using a microphone held by an elastic band
      directly against the patient's skin at the level of the cricoid cartilage.
      Analysis was done on the average of three forced expirations made after a deep
      inspiration. The Hurst's coefficient was computed by Hurst's rescaled range
      analysis (H) and by analysis of the variance-time relationship of the aggregated
      process (H_v). RESULTS: Values of H and H_v were around 0.75, indicating that the
      sound signals were fractal over time. The responses of controls and patients to
      bronchodilator administration of 1 mg terbutaline were similar (p>0.05). Mean
      intra-subject variation coefficients were less than 15%. CONCLUSIONS: This
      analysis of tracheal sound during forced expiratory maneuvers confirms the
      dynamic fractal behavior of the respiratory system.

PMID- 14704643
TI  - A comparison of suture retention strengths for three biomaterials.
AB  - BACKGROUND: The suture holding capacity, suture retention strength, and burst
      strength of three biomaterials (Marlex), SIS, and PeriGuard) were evaluated to
      compare their performance characteristics in an ex vivo setting representing the
      immediate postoperative period. MATERIAL/METHODS: A circular defect was created
      in the fascial tissue of the abdominal aponeurosis collected from normal dogs.
      Defects were repaired with either Marlex (polypropylene mesh), Periguard (bovine
      pericardium) or small intestinal submucosa (SIS) using 2-0 prolene and a 1.0-cm
      suture bite. The force required to induce failure at the repair site was recorded
      as the suture-holding capacity. Suture retention strength was calculated as the
      load distribution over the specimen cross-section in contact with the suture at
      the time of rupture. Burst strength of the raw materials was also measured.
      RESULTS: The suture-holding capacity was 370.9+/-56.2 N for Marlex; 214.3+/-36.1
      N for Periguard, and 287.9+/-34.3 N for SIS. The suture retention strengths were:
      Marlex, 413.4+/-59.7 N/mm2; Periguard, 97.0+/-20.1 N/mm2; and SIS, 106.9+/-12.7
      N/mm2. The burst strength of Marlex, Periguard and SIS were 476.7+/-50.8 N,
      432.12+/-82.1 N, and 433.6+/-79.5 N respectively. CONCLUSIONS: All three
      materials provide adequate strength and suture-holding capacities to be of use in
      the repair of soft tissue defects.

PMID- 14704644
TI  - Is recombinant follicle-stimulating hormone more effective in IVF poor responders
      than human menopausal gonadotrophins?
AB  - BACKGROUND: The objective of this study was to determine if the recombinant human
      follicle-stimulating hormone (rFSH) is more effective than human menopausal
      gonadotrophin (hMG) in IVF poor responders. MATERIAL/METHODS: A prospective
      comparative study over a 2-year period. The setting was the Tertiary IVF Center,
      King Faisal Specialist Hospital and Research Center. A total of 150 patients were
      selected from 277 patients with poor response in previous hMG-stimulated cycles
      who were willing to undergo another cycle of treatment. Seventy-five patients
      stimulated with rFSH were compared with 75 control subjects (matched for age,
      early follicular phase FSH, and body mass index) stimulated with urinary hMG. The
      number of follicles, number of oocytes retrieved, cycle cancellations, and
      pregnancy rates were the main outcome measures. RESULTS: There were no
      statistical differences in numbers of follicles (6.2 versus 5.7; p=0.97), oocytes
      recovered (4 versus 3.3; p=0.15), cycle characteristics, or pregnancy rates
      between hMG- and rFSH-stimulated cycles (p=0.32). CONCLUSIONS: Recombinant
      follicle-stimulating hormone (rFSH) has no advantage over urinary human
      menopausal gonadotrophin (hMG) on ovarian performance or the outcome of IVF-ET in
      poor responders' IVF cycles.

PMID- 14704645
TI  - Presence of anti-preS1, anti-preS2, and anti-HBs antibodies in newborns immunized
      with Bio-Hep-B vaccine.
AB  - BACKGROUND: An advantage of the third-generation HBV vaccines containing preS1
      and preS2 antigens was suggested by their excellent immunogenicity in humans and
      the rapid onset of antibody response to the S-protein of the vaccine. Sequential
      studies of the antibody responses to the preS1 and preS2 in relation to the anti
      HBs response after immunization with preS-containing vaccines have been made in
      older children only. MATERIAL/METHODS: Twenty-eight randomly selected, healthy
      newborns received either 2.5 microg or 5 microg of Bio-Hep-B (preS1, 2+S)
      vaccine. The children received 3 doses of vaccine according to a 0, 1, 6 months
      scheme. Antibodies were determined at months 6 and 9. RESULTS: The vaccine was
      well tolerated and safe in newborns. Seroconversion and seroprotection were
      achieved in 100% of newborns after the second injection. No dose-related effect
      on the anti-HBs response could be observed; GMTs of anti-HBs antibodies after the
      2.5 microg and 5.0 microg doses were 6703 and 7104 Kg IU/l, respectively. The
      induction of measurable levels of antibodies towards preS1- and/or preS2-antigens
      with 2.5 microg and 5 microg doses of the vaccine was noted in 29% and 50% of the
      newborns, respectively, at 6 and/or 9 months of vaccination. An augmented anti
      HBs response was elicited in the newborns who produced anti-preS2 after
      vaccination with 2.5 microg compared with 5.0 microg of the vaccine. CONCLUSIONS:
      The vaccine Bio-Hep-B can elicit high titers of anti-HBs antibodies in newborns
      after only two injections. The response of newborns was directed against preS1 +
      preS2, or preS2 alone.

PMID- 14704646
TI  - How a test for elastic fiber breakdown products in sputum could speed development
      of a treatment for pulmonary emphysema.
AB  - Pulmonary emphysema is a devastating disease for which there is no effective
      treatment. The development of therapeutic agents for this disorder has been
      hampered by the lack of clinical or biochemical tests which can rapidly evaluate
      drug efficacy. Since emphysema is associated with degradation of elastic fibers,
      the authors propose measuring the content of the elastin-specific amino acids,
      desmosine and isodesmosine, in sputum as a more immediate means of monitoring
      therapeutic interventions. Sputum samples would be chemically degraded to
      separate the component amino acids of elastic fibers, then measured for the total
      quantity of desmosine and isodesmosine, using any one of a number of established
      methods for quantifying these compounds, including radioimmunoassay,
      chromatography, or mass spectrometry. Such techniques allow for detection of
      nanogram quantities of desmosine and isodesmosine, and the procurement of ample
      amounts of induced sputum from the lower respiratory tract should improve the
      chances of detecting these amino acids. If proven valid, such a test could serve
      as a convenient marker for assessing lung injury in pulmonary emphysema, thereby
      facilitating rapid evaluation of new forms of treatment for this disease. The
      test might also prove to be a useful screening procedure for persons who smoke or
      otherwise have a greater than normal risk of developing emphysema.

PMID- 14704647
TI  - Multidrug resistance P-glycoprotein: crucial significance in drug disposition and
      interaction.
AB  - This article reviews recent advances in our understanding of the structure, drug
      interaction mechanism, and substrate molecular requirements of P-glycoprotein (P
      gp) and its emerging crucial role in drug disposition and the modulation of drug
      interaction. In view of its wide localization in normal tissues, the broad
      variety of structurally and functionally unrelated substrates of P-gp, and its
      ATP-dependent outward-oriented transport, P-gp actively participates in
      intestinal secretion, blood-tissue barriers, and biliary and renal excretions for
      many exogenous substrates, and also performs a protective role to prevent entry
      of xenobiotics. Moreover, the importance of P-gp-mediated drug interactions in
      clinical practice can hardly be underestimated, since it may result in severe
      side effects, such as digitalis drug interaction. Polymorphism or single
      nucleotide polymorphism (SNP) associated with P-gp may exert a significant effect
      on the pharmacokinetic behavior of its substrates, a fact which has major
      clinical implications and suggests careful dose adjustment for individual
      treatment. Moreover, dietary components and pharmaceutical excipients may
      modulate P-gp activity, and as a result affect in vivo drug disposition and
      therapeutic efficacy; examples include grapefruit juice, Pluronic P85, PEG 300,
      etc. In summary, it should be emphasized that P-gp is an integral component in
      the process of drug discovery, development strategy,

PMID- 14704648
TI  - Prenatal HIV testing and antiretroviral prophylaxis at an urban hospital-
      Atlanta, Georgia, 1997-2000.
AB  - In 1994, the U.S. Public Health Service (USPHS) recommended the use of zidovudine
      (ZDV) to reduce perinatal human immunodeficiency virus (HIV) transmission; in
      1995, USPHS recommended universal prenatal HIV counseling and voluntary testing.
      Widespread implementation of these recommendations, together with increased use
      of antiretroviral therapy (ART) and scheduled cesarean delivery, has resulted in
      substantial declines in perinatal HIV transmission. However, perinatal HIV
      transmission continues to occur. To identify missed prevention opportunities, CDC
      analyzed the incidence of perinatal HIV infection among a cohort of HIV-exposed
      infants born during 1997-2000 at Grady Memorial Hospital (GMH) in Atlanta,
      Georgia. This report describes the results of that analysis and underscores the
      challenges to universal prevention of infant HIV infections. Efforts to reduce
      perinatal HIV transmission should focus on increasing prenatal care rates,
      promoting adherence to recommended treatment regimens during pregnancy, and
      increasing prenatal HIV testing, particularly in areas where missed opportunities
      for prevention of perinatal HIV transmission persist.

PMID- 14704649
TI  - Implementation of named HIV reporting--New York City, 2001.
AB  - Since 1981, population-based surveillance data on acquired immunodeficiency
      syndrome (AIDS) have been used in New York City (NYC) to monitor the human
      immunodeficiency virus (HIV) epidemic. In June 2000, the NYC Department of Health
      and Mental Hygiene (NYCDOHMH) began tracking diagnoses of HIV (non-AIDS) in
      addition to AIDS diagnoses. This report describes epidemiologic data from the
      first full calendar year of named HIV reporting in NYC. The findings indicate
      that, compared with persons living with AIDS (PLWA), persons who had HIV
      diagnosed during 2001 were more likely to be female, non-Hispanic black, younger
      (i.e., aged <45 years), and residents of the Bronx or Brooklyn. These newly
      available data describe the NYC population with HIV infection more accurately
      than data on PLWA and can be used to redirect HIV-prevention efforts to better
      target persons at highest risk for acquiring HIV infection.

PMID- 14704650
TI  - Incidence of acute hepatitis B--United States, 1990-2002.
AB  - Hepatitis B virus (HBV) is a bloodborne and sexually transmitted virus that is
      acquired by percutaneous and mucosal exposure to blood or other body fluids of an
      infected person. Clinical manifestations of acute hepatitis B can be severe, and
      serious complications (i.e., cirrhosis and liver cancer) are more likely to
      develop in chronically infected persons. In the United States, approximately 1.2
      million persons have chronic hepatitis B virus (HBV) infection and are sources
      for HBV transmission to others. However, since the late 1980s, the incidence of
      acute hepatitis B has declined steadily, especially among vaccinated children. To
      characterize the epidemiology of acute hepatitis B in the United States, CDC
      analyzed national notifiable disease surveillance data for 1990-2002. This report
      summarizes the results of that analysis, which indicated that, during 1990-2002,
      the incidence of reported acute hepatitis B declined 67%. This decline was
      greatest among children and adolescents, indicating the effect of routine
      childhood vaccination. The decline was lowest among adults, who accounted for the
      majority of cases; incidence increased among adults in some age groups. To reduce
      HBV transmission further in the United States, hepatitis B vaccination programs
      are needed that target men who have sex with men (MSM), injection-drug users
      (IDUs), and other adults at high risk.

PMID- 14704651
TI  - Update: influenza-associated deaths reported among children aged <18 years-
      United States, 2003-04 influenza season.
AB  - Since October, 42 influenza-associated deaths among children aged <18 years have
      been reported to CDC. All patients had influenza virus infection detected by
      rapid antigen testing or other laboratory testing methods. This report describes
      preliminary findings based on data provided from multiple states, as of December
      17, 2003. To improve surveillance, CDC has requested that all influenza
      associated deaths of children aged <18 years be reported to CDC through state
      health departments.

PMID- 14704652
TI  - Update: influenza activity--United States, December 14-20, 2003.
AB  - Influenza activity in the United States continued to increase during December 14
      20, 2003. The proportion of patient visits to sentinel providers for influenza
      like illness (ILI) overall was 7.7%, which is above the national baseline of
      2.5%. Influenza activity was reported as widespread by health departments in 45
      states, New York City, and the District of Columbia; four states reported
      regional influenza activity; and one state reported local influenza activity.

PMID- 14704653
TI  - A novel preparative regimen for autologous transplant in non-Hodgkin's lymphoma:
      long-term experience with etoposide and thiotepa.
AB  - The purpose of this study was to evaluate the efficacy and toxicity of the
      preparative regimen of thiotepa and etoposide in patients undergoing autologous
      transplantation for relapsed non-Hodgkin's lymphoma. The study involved 65
      consecutive patients who underwent autologous transplantation using the
      thiotepa/etoposide regimen for relapsed intermediate-grade NHL at the University
      of Wisconsin Hospital and Clinics (UWHC) between 1987 and 2001. The regimen
      consisted of thiotepa 300 mg/m(2)/day and etoposide 700 mg/m(2)/day on days -6, 
      5, and -4. The median age at the time of transplant was 49 years. A total of 50
      patients (76%) had diffuse large-cell lymphoma. A total of 50 (77%) patients had
      chemosensitive disease, and 15 (23%) were chemoresistant. With a median follow-up
      of 34 months (range, 3-163), 28 patients (43%) remain in CR and 33 (51%) have
      developed recurrent or progressive disease. The overall survival and event-free
      survival at 3 years are 40% (95% CI 26-53%) and 32% (95% CI 20-45%),
      respectively. There was one death attributed to regimen-related toxicity (RRT).
      Reversible gastrointestinal toxicity was the major RRT, and there was minimal
      pulmonary and cardiac toxicity. We conclude that the combination of thiotepa and
      etoposide is an effective preparative regimen with acceptable RRT.

PMID- 14704654
TI  - Transplantation of highly purified peripheral-blood CD34+ progenitor cells from
      related and unrelated donors in children with nonmalignant diseases.
AB  - Transplantation of allogeneic stem cells is currently the only curative treatment
      for some nonmalignant pediatric diseases. We investigated whether transplantation
      of purified CD34(+) stem cells prevents acute and chronic GvHD and reduces
      transplant-related mortality. A total of 25 pediatric patients with nonmalignant
      diseases underwent allogeneic transplantation from 26 donors (matched related
      n=4, matched or partially matched unrelated n=14, mismatched related n=8). All
      grafts were purified peripheral-blood CD34(+) stem cells mobilized with G-CSF.
      Patients received a median of 12.9 x 10(6) CD34(+) progenitor cells with a median
      of 6.1 x 10(3) contaminating T-lymphocytes per kilogram of body weight. No post
      transplant immunosuppressive drugs were given for prophylaxis of GvHD.
      Engraftment was seen in 21 patients. Three patients engrafted after a second
      transplant and one patient failed to engraft. Two patients had autologous
      reconstitution 1.5 years post transplant and one of them was successfully
      retransplanted. No acute GvHD >grade II was seen, and only two patients developed
      limited, chronic GvHD. In all, 22 patients (88%) are alive with a median follow
      up of 3.7 years. In total, 19 patients (76%) are free of disease or of
      progression. Transplantation of highly purified peripheral-blood CD34(+) stem
      cells is associated with low toxicity in patients with nonmalignant diseases.

PMID- 14704655
TI  - Umbilical cord blood transplant for adult patients with severe aplastic anemia
      using anti-lymphocyte globulin and cyclophosphamide as conditioning therapy.
AB  - Allo-CBSCT (cord blood stem cell transplant) has been applied in six adult
      patients with severe aplastic anemia (SAA). Anti-lymphocyte globulin (ALG) 40 mg
      kg(-1) d(-1) x 3 days combined with cyclophosphamide (CTX) 20 mg kg(-1) d(-1) x 3
      days constituted a lower intensive conditioning regimen. The prophylaxis of GVHD
      consisted of standard CsA and MTX. Patients are all male having a mean age of
      26.5 years (range 22-38), and a median weight of 55.6 kg (range 52-60 kg). Cord
      blood searches were all conducted at Guangzhou Cord Blood Bank. Three of six
      patients in our study received one unit of cord blood in a procedure, whereas for
      another three patients, two units of cord blood (double units) were infused at
      the same time in a transplant protocol. The nine units of umbilical cord blood
      (UCB) infused contained 1.6-10.7 x 10(7) nucleated cells/kg body weight of the
      recipient after thawing. HLA antigens were identical in one unit, 1 antigen
      mismatched in seven, 2 antigens mismatched in 1. As of February 2003, after a
      median follow up of 20 months (range 7-50), four patients are alive and disease
      free. Five patients engrafted with molecular biology analyses showing donor
      recipient mixed chimerism post transplant which is stable and persistent. One
      patient died of severe infection in the third month from transplant and another
      patient died in the early stage post transplant of serious aspergillus infection
      without evidence of engraftment.

PMID- 14704656
TI  - Poor correlation of kinetics between BCR-ABL and WT1 transcript levels after
      allogeneic stem cell transplantation.
AB  - After allogeneic stem cell transplantation (SCT), we evaluated the use of the
      Wilms' tumor gene (WT1) as a minimal residual disease (MRD) marker in 32 patients
      (28 chronic myeloid leukemia, three acute lymphoblastic leukemia and one acute
      myeloid leukemia). All patients expressed BCR-ABL and the kinetics of WT1 were
      compared with those of BCR-ABL using real-time quantitative PCR. WT1 expression
      was seen in the peripheral blood (PB) of healthy controls with a median
      expression level of 7 x 10(-5) (WT1/ABL ratio). The corresponding values for BCR
      ABL-negative and BCR-ABL-positive patient samples were 1 x 10(-4) and 1.6 x 10(
      4), respectively. Kinetic studies in individual patients showed that WT1 and BCR
      ABL levels usually did not copy each other. In four out of six patients who
      relapsed, an increase in WT1 from the background level (10(-4)) was observed only
      at the time of or after relapse, and in two patients increasing WT1 levels were
      observed before the relapse. In addition, the WT1 values found at the time of
      relapse were only two logs higher than the background level, indicating a
      sensitivity of 10(-2). In conclusion, there is a constitutive low expression of
      WT1 in normal hematopoietic cells. The sensitivity and ability of WT1 to predict
      a relapse were poor in this study.

PMID- 14704657
TI  - High-dose therapy/autologous stem cell transplantation in patients with
      chemosensitive multiple myeloma: predictors of complete remission.
AB  - High-dose therapy (HDT) followed by autologous stem cell support is widely used
      as intensification treatment in patients with multiple myeloma (MM) responsive to
      the initial chemotherapy. However, there is growing evidence that only the subset
      of patients who achieve complete remission (CR) actually benefit from this
      approach. The aim of this study was to identify pretransplant predictors of CR in
      responding myeloma patients intensified with HDT. A total of 59 patients with
      chemosensitive disease received myeloablative therapy. The intensification
      regimen consisted of MEL-200 (23), MEL-140/TBI 12 Gy (21) or busulfan-based
      regimens (15). Serum and urine negative immunofixation were required for CR.
      After HDT, the CR rate increased from 8 to 37%. For the overall series, the
      median event-free survival (EFS) and overall survival (OS) from the initiation of
      therapy were 41 and 68 months, respectively. Patients who achieved CR had an EFS
      (median 47 vs 36 months; P=0.023) as well as an OS (median not reached vs 60
      months; P=0.006) significantly longer than those attaining a lower degree of
      response. Finally, the pretransplant features significantly associated to CR were
      a low M-protein size (serum </=10 g/l and urine <0.5 g/24 h) (P=0.0003) and a
      proportion of bone marrow plasma cells of </=5% (P=0.02).

PMID- 14704658
TI  - Combined standard graft-versus-host disease (GvHD) prophylaxis with mycophenolate
      mofetil (MMF) in allogeneic peripheral blood stem cell transplantation from
      unrelated donors.
AB  - In this open single-centre phase II study, MMF was added on day +10 after
      allogeneic transplantation to standard immunosuppressive prophylaxis consisting
      of cyclosporine and methotrexate to decrease the incidence of GvHD. In all, 30
      patients aged 20-59 years with advanced haematological malignancies received an
      unmanipulated blood-stem-cell graft (median of 8.5 x 10(6) CD34(+) and 349 x
      10(6) CD3(+) cells per bodyweight) from matched unrelated (n=26), or mismatched
      donors (n=4). Prior to transplantation, 13 patients underwent fractionated total
      body irradiation and cyclophosphamide, one patient additional etoposide. In all,
      16 patients received reduced conditioning of fludarabin, busulfan, and
      antithymocyte globulin. All patients engrafted in a median of 12 days, and 19
      developed acute GvHD>/=II, including two patients with GvHD III and three with
      GvHD IV. Subsequently, nine patients developed limited and two patients extensive
      chronic GvHD. With a median follow-up of 28 months, the overall survival is 53.3%
      and disease-free survival 50%, respectively. Only two deaths were due to GvHD IV.
      Out of 13 patients, 10 being CMV IgG positive became positive for pp65. In
      conclusion, this MMF schedule seems to be safe and feasible in the prophylaxis of
      severe acute GvHD for high-risk patients, restricted by an increased risk for
      reactivating CMV in seropositive patients.

PMID- 14704659
TI  - Measurable immune dysfunction and telomere attrition in long-term allogeneic
      transplant recipients.
AB  - This study was conducted to determine if the accelerated telomere attrition that
      occurs as a consequence of allogeneic stem cell transplantation leads to
      measurable functional defects. Telomere lengths in mononuclear leukocytes
      obtained from 15 long-term allogeneic stem cell transplant recipients and their
      respective donors were determined by Southern hybridization and densitometric
      analysis. Functional assays evaluated the ability of these cells to proliferate
      in response to a mitogenic stimulus and to differentiate under appropriate
      cytokine stimulation. Lymphocyte proliferation in response to phytohemagglutinin
      was determined by measurement of (3)[H]thymidine uptake. The ability of
      circulating myeloid cells to differentiate was determined after incubation of
      peripheral blood mononuclear cells with IL-3 and GM-CSF. A total of 13 patients
      demonstrated telomeric loss, ranging from 0.1 to 3.7 kbp. Strikingly, lymphocytes
      from 14 of the 15 patients demonstrated a significant decrease in proliferation
      when compared to their respective donors (68%+/-22, P=0.001). All patients
      demonstrated at least a 50% decrease in the number of myeloid colony-forming
      units when compared to their respective donors (P<0.0001). A decreased ability of
      hematopoietic cells to proliferate and differentiate is phenotypically consistent
      with an aged immune system. This may correlate with diminished clinically
      relevant immune responses to infection or vaccination, as seen in the elderly.

PMID- 14704660
TI  - Viridans streptococcal septicaemia in neutropenic patients: role of
      proinflammatory cytokines.
AB  - The immunostimulatory activity of viridans streptococcal strains isolated from
      neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10)
      was compared. Peripheral blood mononuclear cells from healthy individuals were
      stimulated with heat-killed bacteria or culture supernatants, and cytokine
      production assessed. All strains were potent inducers of IL1beta, IL8, and
      TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and
      TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The
      strains did not induce any proliferative response, nor any significant TNFbeta or
      IFNgamma production. No difference in cytokine-inducing capacity could be
      detected between the cohorts of severe and nonsevere isolates. Comparison of
      strains causing severe and nonsevere episodes in the same patient (n=2) revealed
      a significantly higher induction of IL1beta by the severe episodes associated
      isolates as compared to the nonsevere (P<0.04). The study underscores the
      importance of the host-pathogen interplay in determining the level of
      inflammation, and hence the severity of disease.

PMID- 14704661
TI  - Relationship between circulating cytokine levels and thyroid function following
      bone marrow transplantation.
AB  - The relation between thyroid hormone changes and cytokines in bone marrow
      transplantation (BMT) patients has not been studied. This prospective study was
      designed to determine the relation between thyroid hormones and cytokine levels
      after BMT and their effects on the mortality. We studied 80 patients undergoing
      allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were
      measured before and serially during 6 months after BMT. Serum T(3) decreased to a
      nadir 3 weeks post-BMT and serum T(4) was lowest at 3 months post-BMT. Serum
      thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and
      recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined
      thereafter. Serum tumor necrosis factor-alpha increased for 3 weeks after BMT and
      declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively
      correlated with serum T(3) and T(4) levels. A total of 29 patients died before 1
      year post-BMT and 51 patients survived longer than 1 year. Those patients who
      died before 1 year post-BMT had significantly lower levels of T(4) at 3 weeks, 3
      and 6 months than surviving patients. In conclusion, increased levels of serum IL
      6 and TNF-alpha were negatively correlated with thyroid hormone concentrations in
      BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

PMID- 14704662
TI  - T-cell large granular lymphocytic leukemia occurring after autologous peripheral
      blood stem cell transplantation.
AB  - A 61-year-old man with angioimmunoblastic lymphoma in first complete remission
      underwent autologous peripheral blood stem cell transplantation. At 1 month post
      transplant, asymptomatic large granular lymphocytosis developed. The surface
      marker profile of the cells was CD3+CD8+CD56-CD57+. The disease course was
      chronic and indolent. The patient remains in complete remission from
      angioimmunoblastic lymphoma more than 6 months post transplant with persistent
      large granular lymphocytosis (lymphocyte count, 5-15 x 10(9)/l). Although post
      transplantation T-cell lymphoproliferative disorders have mostly occurred in
      allogeneic transplantation recipients and presented as aggressive
      lymphomas/leukemias, we suggest that chronic indolent T-cell large granular
      lymphocytic leukemia can occur after autologous stem cell transplantation.

PMID- 14704663
TI  - Successful treatment of JMML relapsed after unrelated allogeneic transplant with
      cytoreduction followed by DLI and interferon-alpha: evidence for a graft-versus
      leukemia effect in non-monosomy-7 JMML.
AB  - Relapse is the major cause of treatment failure after allogeneic transplantation
      of children with juvenile myelomonocytic leukemia (JMML), and the role of post
      transplant immunomodulation is poorly understood. We report a 12-month-old child
      with JMML relapsed after unrelated marrow transplantation who received
      cytoreduction followed by donor lymphocyte infusion (DLI) with improvement, and
      after addition of interferon-alpha (IFN) achieved complete donor chimerism. He
      was weaned from IFN and has maintained complete remission for 19 months. This is
      the first published report of a patient with non-monosomy-7 JMML responding to
      post-transplant immunomodulation and suggests a role for DLI plus IFN in these
      patients.

PMID- 14704664
TI  - Strongyloidiasis pre and post autologous peripheral blood stem cell
      transplantation.

PMID- 14704665
TI  - Nonconvulsive status epilepticus associated with cefepime in a patient undergoing
      autologous stem cell transplantation.

PMID- 14704667
TI  - Intense and highly localized gene conversion activity in human meiotic crossover
      hot spots.
AB  - Meiotic gene conversion has an important role in allele diversification and in
      the homogenization of gene and other repeat DNA sequence families, sometimes with
      pathological consequences. But little is known about the dynamics of gene
      conversion in humans and its relationship to meiotic crossover. We therefore
      developed screening and selection methods to characterize sperm conversions in
      two meiotic crossover hot spots in the major histocompatibility complex (MHC) and
      one in the sex chromosomal pseudoautosomal pairing region PAR1 (ref. 9). All
      three hot spots are active in gene conversion and crossover. Conversion tracts
      are short and define a steep bidirectional gradient centered at the peak of
      crossover activity, consistent with crossovers and conversions being produced by
      the same recombination-initiating events. These initiations seem to be spread
      over a narrow zone, rather than occurring at a single site, and seem
      preferentially to yield conversions rather than crossovers. Crossover breakpoints
      are more broadly diffused than conversion breakpoints, suggesting either
      differences between conversion and crossover processing after initiation or the
      existence of a quality control checkpoint at which short interactions between
      homologous chromosomes are preferentially aborted as conversions.

PMID- 14704668
TI  - Restriction enzyme-generated siRNA (REGS) vectors and libraries.
AB  - Small interfering RNA (siRNA) technology facilitates the study of loss of gene
      function in mammalian cells and animal models, but generating multiple siRNA
      vectors using oligonucleotides is slow, inefficient and costly. Here we describe
      a new, enzyme-mediated method for generating numerous functional siRNA constructs
      from any gene of interest or pool of genes. To test our restriction enzyme
      generated siRNA (REGS) system, we silenced a transgene and two endogenous genes
      and obtained the predicted phenotypes. REGS generated on average 34 unique siRNAs
      per kilobase of sequence. REGS enabled us to create enzymatically a complex siRNA
      library (>4 x 10(5) clones) from double-stranded cDNA encompassing known and
      unknown genes with 96% of the clones containing inserts of the appropriate size.

PMID- 14704669
TI  - Enzymatic production of RNAi libraries from cDNAs.
AB  - RNA interference (RNAi) induced by small interfering (siRNA) or short hairpin RNA
      (shRNA) is an important research approach in mammalian genetics. Here we describe
      a technology called enzymatic production of RNAi library (EPRIL) by which cDNAs
      are converted by a sequence of enzymatic treatments into an RNAi library
      consisting of a vast array of different shRNA expression constructs. We applied
      EPRIL to a single cDNA source and prepared an RNAi library consisting of shRNA
      constructs with various RNAi efficiencies. High-throughput screening allowed us
      to rapidly identify the best shRNA constructs from the library. We also describe
      a new selection scheme using the thymidine kinase gene for obtaining efficient
      shRNA constructs. Furthermore, we show that EPRIL can be applied to constructing
      an RNAi library from a cDNA library, providing a basis for future whole-genome
      phenotypic screening of genes.

PMID- 14704670
TI  - Molecule pages live.

PMID- 14704671
TI  - Controlling Abl: auto-inhibition and co-inhibition?
AB  - Auto-inhibition describes the capacity of proteins to adopt a self-imposed latent
      conformation. Recently, a crystal structure of the Abl tyrosine kinase has
      revealed its ability to auto-inhibit. However, a separate body of work suggests
      that other cellular proteins also inhibit Abl. To reconcile the crystal structure
      with Abl inhibitors, I propose that Abl is controlled by cellular 'co-inhibitors'
      that bind Abl, stabilizing the auto-inhibited conformation. The implication of co
      inhibition on Abl function is discussed.

PMID- 14704673
TI  - Sweet control of cell migration, cytokinesis and organogenesis.

PMID- 14704674
TI  - Formin' adherens junctions.

PMID- 14704676
TI  - Lipid pickup and delivery.

PMID- 14704677
TI  - No glial death with NO.

PMID- 14704682
TI  - Discovery of transdermal penetration enhancers by high-throughput screening.
AB  - Although transdermal drug delivery is more attractive than injection, it has not
      been applied to macromolecules because of low skin permeability. Here we describe
      particular mixtures of penetration enhancers that increase skin permeability to
      macromolecules (approximately 1-10 kDa) by up to approximately 100-fold without
      inducing skin irritation. The discovery of these mixtures was enabled by an
      experimental tool, in vitro skin impedance guided high-throughput (INSIGHT)
      screening, which is >100-fold more efficient than current tools. In vitro
      experiments demonstrated that the mixtures delivered macromolecular drugs,
      including heparin, leutinizing hormone releasing hormone (LHRH) and
      oligonucleotides, across the skin. In vivo experiments on hairless rats with
      leuprolide acetate confirmed the potency and safety of one such mixture, sodium
      laureth sulfate (SLA) and phenyl piperazine (PP). These studies show the
      feasibility of using penetration enhancers for systemic delivery of
      macromolecules from a transdermal patch.

PMID- 14704683
TI  - Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal
      transduction.
AB  - The erbB/HER family of transmembrane receptor tyrosine kinases (RTKs) mediate
      cellular responses to epidermal growth factor (EGF) and related ligands. We have
      imaged the early stages of RTK-dependent signaling in living cells using: (i)
      stable expression of erbB1/2/3 fused with visible fluorescent proteins (VFPs),
      (ii) fluorescent quantum dots (QDs) bearing epidermal growth factor (EGF-QD) and
      (iii) continuous confocal laser scanning microscopy and flow cytometry. Here we
      demonstrate that EGF-QDs are highly specific and potent in the binding and
      activation of the EGF receptor (erbB1), being rapidly internalized into endosomes
      that exhibit active trafficking and extensive fusion. EGF-QDs bound to erbB1
      expressed on filopodia revealed a previously unreported mechanism of retrograde
      transport to the cell body. When erbB2-monomeric yellow fluorescent protein
      (mYFP) or erbB3-monomeric Citrine (mCitrine) were coexpressed with erbB1, the
      rates and extent of endocytosis of EGF-QD and the RTK-VFP demonstrated that erbB2
      but not erbB3 heterodimerizes with erbB1 after EGF stimulation, thereby
      modulating EGF-induced signaling. QD-ligands will find widespread use in basic
      research and biotechnological developments.

PMID- 14704684
TI  - The one that got away.

PMID- 14704685
TI  - China approves first gene therapy.

PMID- 14704686
TI  - Vatican debates agbiotech.

PMID- 14704687
TI  - UK to pursue contract clinical trials.

PMID- 14704688
TI  - Cancer trials get set for biomarkers.

PMID- 14704689
TI  - Chile launches policy to boost biotech.

PMID- 14704690
TI  - Nasdaq dilutes its biotech index.

PMID- 14704692
TI  - Signal transduction inhibitors--a work in progress.

PMID- 14704693
TI  - Health impact of nanomaterials?

PMID- 14704694
TI  - Realities for Latin American and Caribbean biotech.

PMID- 14704695
TI  - The emerging role of academia in commercializing innovation.

PMID- 14704696
TI  - Do cloned mammals skip a reprogramming step?

PMID- 14704697
TI  - How do your stocks really perform?

PMID- 14704699
TI  - Old dogma, new tricks--21st Century phage therapy.
AB  - As antibiotic resistant bacteria threaten a public health crisis, biotechnology
      is turning to bacteriophages, nature's tiniest viruses. But can phage therapy
      overcome its historical baggage?

PMID- 14704700
TI  - The biological magic behind the bullets.

PMID- 14704701
TI  - Cancer surgery joins the dots.

PMID- 14704702
TI  - Rain or shine--a phototroph that delivers.

PMID- 14704703
TI  - Unnatural selection of cultured human ES cells?

PMID- 14704704
TI  - Protein interaction maps on the fly.

PMID- 14704706
TI  - The use of nanocrystals in biological detection.
AB  - In the coming decade, the ability to sense and detect the state of biological
      systems and living organisms optically, electrically and magnetically will be
      radically transformed by developments in materials physics and chemistry. The
      emerging ability to control the patterns of matter on the nanometer length scale
      can be expected to lead to entirely new types of biological sensors. These new
      systems will be capable of sensing at the single-molecule level in living cells,
      and capable of parallel integration for detection of multiple signals, enabling a
      diversity of simultaneous experiments, as well as better crosschecks and
      controls.

PMID- 14704707
TI  - Complete genome sequence of the metabolically versatile photosynthetic bacterium
      Rhodopseudomonas palustris.
AB  - Rhodopseudomonas palustris is among the most metabolically versatile bacteria
      known. It uses light, inorganic compounds, or organic compounds, for energy. It
      acquires carbon from many types of green plant-derived compounds or by carbon
      dioxide fixation, and it fixes nitrogen. Here we describe the genome sequence of
      R. palustris, which consists of a 5,459,213-base-pair (bp) circular chromosome
      with 4,836 predicted genes and a plasmid of 8,427 bp. The sequence reveals genes
      that confer a remarkably large number of options within a given type of
      metabolism, including three nitrogenases, five benzene ring cleavage pathways and
      four light harvesting 2 systems. R. palustris encodes 63 signal transduction
      histidine kinases and 79 response regulator receiver domains. Almost 15% of the
      genome is devoted to transport. This genome sequence is a starting point to use
      R. palustris as a model to explore how organisms integrate metabolic modules in
      response to environmental perturbations.

PMID- 14704708
TI  - Gaining confidence in high-throughput protein interaction networks.
AB  - Although genome-scale technologies have benefited from statistical measures of
      data quality, extracting biologically relevant pathways from high-throughput
      proteomics data remains a challenge. Here we develop a quantitative method for
      evaluating proteomics data. We present a logistic regression approach that uses
      statistical and topological descriptors to predict the biological relevance of
      protein-protein interactions obtained from high-throughput screens for yeast.
      Other sources of information, including mRNA expression, genetic interactions and
      database annotations, are subsequently used to validate the model predictions
      without bias or cross-pollution. Novel topological statistics show hierarchical
      organization of the network of high-confidence interactions: protein complex
      interactions extend one to two links, and genetic interactions represent an even
      finer scale of organization. Knowledge of the maximum number of links that
      indicates a significant correlation between protein pairs (correlation distance)
      enables the integrated analysis of proteomics data with data from genetics and
      gene expression. The type of analysis presented will be essential for analyzing
      the growing amount of genomic and proteomics data in model organisms and humans.

PMID- 14704709
TI  - Systematic identification of sense-antisense transcripts in mammalian cells.
AB  - In prokaryotes, a number of endogenous antisense RNAs have been detected and
      found to exert various biological functions. In eukaryotes antisense RNAs have
      been found; however, a lack of experimental methodologies that permit the
      identification of overlapping transcripts in cells presents a barrier to a more
      systematic identification of antisense RNA. Here we have developed an
      experimental strategy that allows systematic identification of endogenous mRNAs
      with long complementary regions to other transcripts. The method was applied to
      human normal mammary epithelial and breast cancer cells. Experimental validation
      of the presence of the sense and antisense transcripts by various techniques
      (e.g., northern blots, RT-PCR) supports the specificity of the method. When the
      antisense RNAs were specifically targeted, their corresponding mRNA levels
      significantly altered, a result consistent with a regulatory role for the
      identified antisense RNAs.

PMID- 14704710
TI  - Patent protection for protein structure analysis.
AB  - Three national patent offices have consulted on patents that cover protein three
      dimensional structural data and pharmacophores, with significant implications for
      the biotechnology industry.

PMID- 14704715
TI  - Does your chairman need to be Superman?
AB  - To find the right chairman for your biotechnology company, brush up on your
      chemistry skills.

PMID- 14704716
TI  - Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and
      occludin in synovial sarcoma: an immunohistochemical study with ultrastructural
      correlation.
AB  - Synovial sarcoma demonstrates epithelial differentiation, either by light
      microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural
      methods only (monophasic) and poorly differentiated synovial sarcoma. Although
      the glands of synovial sarcoma are known to have tight junction-like structures,
      far less is known about junction formation in the spindled component of synovial
      sarcomas. Additionally, it is unknown whether the tight junctions of synovial
      sarcoma are normally constituted. The tight junction is a multiprotein complex
      consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A
      total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight
      poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using
      commercially available antibodies, heat-induced epitope retrieval and standard
      avidin-biotin technique. When available, corresponding electron micrographs were
      reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT
      SSX2 (two cases) gene fusion was known. Positive cases showed particulate
      membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1
      (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal
      glandular epithelia, at the apical portion of the lateral membrane. The spindle
      cells of biphasic synovial sarcomas showed abnormal circumferential membranous
      expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic
      synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less
      often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial
      sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8).
      By electron microscopy, recognizable tight junctions were seen only in glands. No
      correlation was seen between histologic subtype or fusion type and expression of
      tight junction proteins. We conclude that the glands of biphasic synovial
      sarcomas show well-organized, true epithelial tight junctions. In contrast, the
      spindled cells of all synovial sarcomas show significant abnormalities in the
      expression and localization of tight junction proteins, suggesting partial and/or
      aberrant epithelial differentiation.

PMID- 14704717
TI  - Endobronchial variant of sclerosing hemangioma of the lung: histological and
      cytological features on endobronchial material.
AB  - We report two cases of a rare presentation of pulmonary sclerosing hemangioma as
      an endobronchial polyp resulting in clinical symptoms of bronchial obstruction.
      We describe the histological and cytological description of this entity based on
      material obtained during bronchoscopic examination. In both cases, bronchoscopy
      revealed a polypoid mass protruding into the left lower lobar bronchus, with a
      smooth and hemorrhagic surface, reminiscent of a carcinoid tumor. On bronchial
      washing in case 1, numerous small round cells were seen with uniform nuclei and
      inconspicuous nucleoli, arranged in clusters with a pavement-type pattern and
      papillary configuration. The presence of a few reactive pneumocytes gives a dual
      cell proliferation, in a background of numerous foamy macrophages. Although the
      four architectural patterns of sclerosing hemangioma were present in the resected
      tumors, the papillary and solid patterns predominated in the endobronchial
      component of the tumors and these were seen on the bronchial biopsies.
      Recognition of the papillary pattern, the typical round cells coexpressing
      thyroid transcription factor-1 and epithelial membrane antigen without
      cytokeratin immunoreactivity, are helpful clues for the diagnosis on bronchial
      biopsy. Finally, hopefully awareness by clinicians and pathologists that
      sclerosing hemangioma can present as an endobronchial mass will facilitate
      diagnosis when this rare event occurs.

PMID- 14704718
TI  - Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a
      series of four autopsies.
AB  - We have observed an increasing number of autopsies on patients with chemotherapy
      related complications. One complication is toxic leukoencephalopathy, which is
      due to a direct toxic effect of chemotherapeutic agents on the central nervous
      system white matter. Autopsies of four cases of toxic leukoencephalopathy were
      performed following standard protocols. The brain and spinal cord were examined
      routinely, and histological sections were taken for evaluation. We report here
      three patients with hematologic malignancies and one patient with metastatic
      carcinoma with chemotherapy-induced leukoencephalopathy. The first was a 56-year
      old male treated with multiple chemotherapeutics for multiple myeloma. He
      presented with confusion and focal seizures with a rapid progression to coma and
      decerebrate posturing. The second was a 36-year-old male who developed mental
      status changes, ataxia and dysarthria following treatment for lymphoma. The third
      was a 16-year-old male who developed a profound peripheral and central neuropathy
      after chemotherapy treatment for T-cell acute lymphoblastic leukemia. The fourth
      was a 49-year-old female patient who was treated with multiple chemotherapeutics
      for Stage II breast carcinoma and subsequently developed visual acuity and field
      defects. The neuropathologic findings in these cases, although similar, varied in
      severity and distribution. The white matter was affected by severe myelin pallor,
      edema, and a prominent macrophage infiltrate in each of the cases. The location
      and extent of the central nervous system pathology correlated with the type and
      severity of clinical symptoms. These four cases, with their varied presenting
      symptoms, clinical courses, and degree of pathology, emphasize the importance of
      considering toxic leukoencephalopathy as an etiology of acute neurologic
      deterioration following high-dose chemotherapy.

PMID- 14704719
TI  - Prevention of Fas-mediated hepatic failure by transferrin.
AB  - Recent studies in lymphohemopoietic cells show that transferrin (Tf), a pivotal
      component of iron transport and metabolism, also exerts cytoprotective functions.
      We show here in a murine model that Tf interferes with Fas-mediated hepatocyte
      death and liver failure. The mechanism involves the downregulation of apoptosis
      via BID, cytochrome c, caspase-3 and caspase-9, and upregulation of antiapoptotic
      signals via Bcl-xL. The results obtained with iron-saturated Tf, Apo-Tf and the
      iron-chelator salicylaldehyde isonicotinoyl hydrazone indicate that the observed
      antiapoptotic effect of Tf was not mediated by iron alone. In conclusion, the
      data suggest that Tf has broader functions than previously recognized and may
      serve as a cytoprotective agent.

PMID- 14704720
TI  - Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary
      allograft function.
AB  - Roughly 25% of cadaveric, but rarely living donor renal transplant recipients,
      develop postischemic acute renal failure, which is a main risk factor for reduced
      long-term allograft survival. An accurate prediction of recipients at risk for
      ARF is not possible on the basis of donor kidney morphology or donor/recipient
      demographics. We determined the genome-wide gene-expression pattern using cDNA
      microarrays in three groups of 36 donor kidney wedge biopsies: living donor
      kidneys with primary function, cadaveric donor kidneys with primary function and
      cadaveric donor kidneys with biopsy proven acute renal failure. The descriptive
      genes were characterized in gene ontology terms to determine their functional
      role. The validation of microarray experiments was performed by real-time PCR. We
      retrieved 132 genes after maxT adjustment for multiple testing that significantly
      separated living from cadaveric kidneys, and 48 genes that classified the donor
      kidneys according to their post-transplant course. The main functional roles of
      these genes are cell communication, apoptosis and inflammation. In particular,
      members of the complement cascade were activated in cadaveric, but not in living
      donor kidneys. Thus, suppression of inflammation in the cadaveric donor might be
      a cheap and promising intervention for postischemic acute renal failure.

PMID- 14704721
TI  - Ultrasound-guided left-ventricular catheterization: a novel method of whole mouse
      perfusion for microimaging.
AB  - We describe a novel technique to perform whole-body perfusion fixation in mice
      with specific relevance to micro-imaging. With the guidance of high-frequency
      ultrasound imaging, we were able to perfuse fixative and contrast agents via a
      catheter inserted into the left ventricle, and therefore preserved the integrity
      of the chest and abdominal cavity. In this preliminary study, our success rate
      over 15 animals was 73%. We demonstrate applications of this technique for
      magnetic resonance imaging and micro-CT, but we expect that this method can be
      generally applied to whole-body perfusions of other small animals in which the
      intact body is necessary.

PMID- 14704722
TI  - Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in
      actively inflammatory lesions of human chronic gastritis.
AB  - Chronic gastritis is frequently associated with infection of Helicobacter pylori
      and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma
      cells. To address the mechanism of lymphocyte infiltration in chronic gastritis,
      we examined the expression of chemokines and their receptors using frozen
      sections of chronic gastritis, obtained from 23 patients who underwent
      gastrectomy for gastric cancer. By immunohistochemistry, lymphocytes in inflamed
      gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4
      sparsely. The numbers of CCR5(+) cells, which were composed of mainly CD8(+) and
      partly CD4(+) T cells, were positively correlated with the degree of neutrophil
      infiltration, and decreased in areas with intestinal metaplasia or mucosal
      atrophy. RANTES/CCL5, one of the ligands of CCR5, was localized mainly in CD8(+)
      and partly CD4(+) T cells with a characteristic dotted pattern, and such
      lymphocytes were most densely distributed around the neck region of gastric
      glands. In situ hybridization confirmed the expression of CCL5 mRNA in these
      cells, and immunoelectron microscopy revealed localization of CCL5 in the
      membrane-bound granules, which most probably corresponded to the cytolytic
      granules of cytotoxic T cells. The numbers of CCL5(+) lymphocytes showed a close
      correlation with the degree of neutrophil infiltration and markedly decreased in
      intestinal metaplasia. In conclusion, our data suggest that, together with
      neutrophils, CCL5(+) T cells, presumably activated cytotoxic T cells, would play
      important roles in the active inflammatory process of chronic gastritis. Our data
      also suggest a self-recruiting mechanism involving CCR5 and CCL5 for tissue
      accumulation of such T cells.

PMID- 14704723
TI  - White coat hypertension: not so benign after all?

PMID- 14704724
TI  - White coat hypertension is a cardiovascular risk factor: a 10-year follow-up
      study.
AB  - The objective of this paper was to evaluate the cardiovascular risk in white coat
      hypertension (WCH). WCH is a well-known clinical entity defined by persistently
      elevated blood pressure (BP) in the doctor's office, whereas BP in other
      conditions is normal. The prognosis of WCH is unsettled, although two prospective
      studies that include normal control groups imply that the condition is benign.
      This study is a 10-year follow-up study on 420 patients with grade I-II
      hypertension newly diagnosed by their general practitioner and 146 normal
      controls (NTs). Ambulatory blood pressure (ABP) monitoring was performed at
      baseline. With our protocollated cutoff value of daytime-ABP <135/90 mmHg, 76
      (18.1%) of the 420 hypertensives were white coat hypertensives (WCHs) and 344
      were established hypertensives (EHs). With a lower cutoff of 135/85 mmHg, 40
      (9.5%) were WCHs. Complete follow-up data were obtained for all 566 subjects. The
      mean duration of follow-up was 10.2 years (range 9.0-12.5). In the WCH group, 14
      first events were recorded (18.4%) consisting of two cardiovascular deaths and 12
      nonfatal cardiovascular events. In the EH group, the corresponding number of
      events were 56 first events (16.3%), 12 cardiovascular deaths and 44 nonfatal
      cardiovascular events, and in the NT group 10 first events (6.8%), two
      cardiovascular deaths and eight nonfatal cardiovascular events. The event rate
      was similar in the WCH group and the EH group and significantly lower in the NT
      group (P<0.05). When corrected for daytime-ABP, age and other confounders, the
      difference remained statistically significant. When using the lower cutoff of
      135/85 mmHg, WCH was still associated with a significantly higher cardiovascular
      event rate. In conclusion, the main finding of this 10-year follow-up study is an
      increased cardiovascular risk in WCH compared to normotensive controls.

PMID- 14704725
TI  - Terminal digit bias in a specialty hypertension faculty practice.
AB  - Traditional blood pressure (BP) methodology is subject to observer error such as
      terminal digit preference and single number preference leading to inaccuracies in
      measurement. A high percentage (60-90%) of terminal BP readings digit being zero
      has been reported from general medical- and hospital-based clinics. This study
      examined terminal digit preference in a hypertension specialty practice and
      assessed clinical factors that may be associated with zero preference in this
      setting. A retrospective chart review of patients presenting to the hypertension
      clinic at the University of Connecticut Health Center during the month of
      September 2001 was performed. Data were extracted on age, gender, height, weight,
      treatment status, and systolic and diastolic BP measurements taken by nursing
      staff and attending physicians. Terminal digit preference was apparent in BP
      readings taken by both nursing staff and physicians. Zero was the terminal
      systolic BP digit in 40% of readings taken by the nursing staff and 31% of
      readings taken by physicians. For diastolic BP readings, the percentages were 23
      and 36%, respectively. Nurses also recorded 43% of diastolic BP readings with
      terminal digit 2. Age was significantly higher in those persons in whom the
      physician diastolic BP terminal digit was zero than in those with nonzero
      terminal digits (67+/-14 vs 59+/-18 years, P=0.008). Body mass index was lower in
      the patient group with diastolic terminal digit zero bias compared to those with
      nonzero terminal digits (28+/-5 vs 32+/-6 kg/m(2), P=0.02). In conclusion,
      although the frequency of zero digit preference did not reach the 60-80% levels
      found in previous studies, there was evidence of terminal digit preference in the
      systolic and diastolic measurements taken by nursing staff and attending
      physicians in a specialist hypertension clinic. We believe that the lower levels
      of terminal digit preference observed are an effect of increased training in
      proper BP measurement and technique. However, the observed bias in measurement
      even in a hypertension unit argues for regular monitoring and feedback to
      minimize such errors.

PMID- 14704726
TI  - Clinical decision-making in hypertension using an automated (BpTRU) measurement
      device.
AB  - Mercury sphygmomanometers are being removed from clinical practice in the United
      States due to environmental concerns about mercury toxicity. Accurate blood
      pressure measurement is central to high-quality hypertension management. In this
      study of 106 patients, the BpTRU(TM) device was compared to nurse blood pressure
      measurements that complied with all the JNC VII/American Heart Association
      guidelines in evaluation of a random casual blood pressure. The intermethod
      difference in systolic blood pressure was +1.8+/-5.1 mmHg, and for diastolic
      blood pressure it was 4.8+/-5.1 mmHg (both P<0.001). For the primary study end
      point of clinical decision-making, there was 92% (97/106) agreement between the
      hypertension nurse specialist and the BpTRU (kappa 0.8280, 95% confidence
      interval, 0.721-0.9350). The oscillometric blood pressure measurement with the
      BpTRU is recommended as a replacement for poorly performed auscultatory blood
      pressure measurement in clinical practice.

PMID- 14704727
TI  - Cardiovascular haemodynamic response to repeated mental stress in normotensive
      subjects at genetic risk of hypertension: evidence of enhanced reactivity,
      blunted adaptation, and delayed recovery.
AB  - To identify unique cardiovascular responses to stressors in a population at
      genetic risk of hypertension, we studied haemodynamic responses in initial
      reactivity to, subsequent adaptation to, and final recovery from repeated active
      mental stress in young, normotensive individuals stratified by hypertension
      parental history (PH). Two groups (n=21/group) of normotensive white males
      underwent stress testing. One group (N+PH) had a hypertensive parent, while the
      other group (N-PH) did not. Cardiovascular response was measured before, during,
      and after repeated serial-subtraction math. Initial reactivity was measured as
      the difference between baseline and initial stress response, subsequent
      adaptation as the difference in response to repeated trials, and final recovery
      was assessed by the difference between baseline and postbaseline levels. The
      influence of PH on reactivity, adaptation, and recovery was assessed by repeated
      measures ANOVA for stroke volume, cardiac output, pre-ejection period, total
      peripheral resistance, mean successive heartbeat time difference, blood pressure,
      and heart rate. Multivariate analysis of variance (MANOVA) determined the effect
      of PH on overall reactivity, adaptation, and recovery. As compared to the N-PH
      group, initial reactivity was higher in the N+PH group for cardiac index (P<0.05)
      and pre-ejection period (P<0.05). Subsequent adaptation in the N+PH group was
      significantly slower for pre-ejection period (P=0.03). Finally, the N+PH group
      showed delayed recovery in heart rate (P=0.03), diastolic blood pressure
      (P<0.05), and pre-ejection period (P=0.007). In conclusion, the heightened
      reactivity, lack of adaptation, and delayed recovery occur in the sympathetic
      system of normotensive subjects at genetic risk of hypertension, specifically in
      beta-adrenergic responses (pre-ejection period). The parasympathetic response
      (mean successive heartbeat time difference) was not different. Increased cardiac
      output reactivity in the N+PH group (P<0.05) thus precedes any difference in
      blood pressure reactivity (P<0.99). Delayed recovery of diastolic blood pressure
      is also found in the N+PH group (P<0.05), which suggests lower baroreceptor
      sensitivity. Since delayed recovery in heart rate (P=0.03), and diastolic blood
      pressure (P<0.05) occur in N+PH subjects even before the corresponding changes in
      reactivity (P>0.10) or adaptation (P>0.07) are seen, these recovery impairments
      may be among the earliest precursors to the development of essential hypertension
      in this population. Finally, PH group haemodynamic differences suggest that these
      traits (reactivity, adaptation, and recovery) may constitute early 'intermediate'
      phenotypes in the pathogenesis of hypertension.

PMID- 14704728
TI  - Blood pressure and left ventricular geometric pattern determine diastolic
      function in hypertensive myocardial hypertrophy.
AB  - Abnormal left ventricular (LV) diastolic relaxation is an early sign of
      hypertensive heart disease. Whether LV diastolic dysfunction is caused directly
      by raised blood pressure, or by structural changes related to LV hypertrophy
      remains controversial. We examined 115 hypertensive patients with LV hypertrophy,
      and two age- and gender-matched groups (38 hypertensive patients without LV
      hypertrophy and 38 normotensive subjects) by echocardiography to assess
      determinants of LV diastolic function, and the relation between diastolic
      function and LV geometric pattern. Diastolic function was evaluated by the E/A
      ratio, E wave deceleration time (E-dec), isovolumic relaxation time (IVRT), and
      the atrioventricular plane displacement method (AV-LA/AV-mean). A multivariate
      analysis (including gender, age and body mass index) shows diastolic function to
      be inversely related to blood pressure, LV wall thickness and LV mass, but not to
      LV end diastolic diameter. The E/A-ratio generally showed the strongest
      relations. Only the E/A-ratio and AV-LA/AV-mean were related to heart rate. By
      stepwise regression analysis, age was the strongest determinant for the E/A
      ratio, E-dec and AV-LA/AV-mean, followed by systolic blood pressure, heart rate
      and LV wall thickness. For IVRT, however, LV wall thickness appeared strongest,
      followed by systolic blood pressure and age. In conclusion, blood pressure and LV
      wall thickness both have independent influence on LV diastolic function. Age and
      blood pressure are the most important factors to determine the E/A-ratio and E
      dec, whereas LV geometry and blood pressure are most important when IVRT is used.
      AV-LA/AV-mean may not be useful in hypertensive LV hypertrophy.

PMID- 14704729
TI  - Impact of elevated blood pressure on mortality from all causes, cardiovascular
      diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly
      selected population from Japanese -- Nippon data 80.
AB  - The objectives of the study were to clarify the relationship between blood
      pressure and mortality from stroke, heart disease, cardiovascular diseases and
      all causes of death among representative population of Japanese and to estimate
      category-specific excess mortality from stroke due to blood pressure (BP) level.
      The study design comprised a retrospective cohort study using the 1980 National
      Survey on Cardiovascular Diseases and identification of underlying causes of
      death using national vital statistics data. In 1994, a 14-year follow-up cohort
      study was conducted among participants of the National Survey on Cardiovascular
      Diseases in 1980, randomly selected from the Japanese population. With a
      collaboration of 300 public health centres, which had conducted the original
      survey in 1980, 91.4% of the participants of the original survey could be
      followed up. Total observed person-years were 53948 for men and 70932 for women.
      During follow-up, 1327 deaths were observed. BP levels were significantly related
      to mortality from strokes, cardiovascular diseases and all causes of death for
      both sexes (P<0.001). Heart disease mortality was significantly related to BP
      levels among men (P<0.05) while not among women. Estimated excess mortality was
      130% for men and 42% for women and chiefly observed among moderate hypertensives
      (48% for men and 16% for women). In conclusion, high blood pressure was a risk
      factor for mortality from all causes as well as those from cardiovascular
      diseases, stroke and heart disease among Japanese. Since the major part of excess
      mortality was due to mild hypertension, a population strategy to reduce blood
      pressure should be encouraged.

PMID- 14704730
TI  - Aldosterone synthase alleles and cardiovascular phenotype in young adults.
AB  - The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2)
      gene has been associated with hypertension and cardiac hypertrophy, but there
      were contrasting data. We analysed the genotype/phenotype associations between
      this polymorphism and cardiovascular variables in a young adult population, where
      interactions among genes, gene-environment, and acquired ageing-related organ
      damage are reduced. Anthropometric measurements, blood pressure, heart rate, left
      ventricular variables (by echocardiography), and carotid artery wall intimal
      media thickness (by high-resolution sonography and digitalized morphometry) were
      taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years).
      CYP11B2 alleles were detected by genomic polymerase chain reaction followed by
      digestion. Taking into account the three possible models of inheritance, we found
      no differences in the considered variables, except for an independent effect of
      the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5
      (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in
      diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg,
      P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T
      polymorphism appears to have a slight role in the cardiovascular phenotype of
      young healthy adults, even if these genotype/phenotype relationships might change
      with ageing.

PMID- 14704733
TI  - Complications of obesity: the inflammatory link. Proceedings of an international
      symposium. November 15-16, 2002. Quebec City, Quebec, Canada.

PMID- 14704734
TI  - Complications of obesity: the inflammatory link. Introduction.

PMID- 14704735
TI  - Obesity, inflammation and type II diabetes.

PMID- 14704736
TI  - Cellular mechanism of insulin resistance: potential links with inflammation.
AB  - Insulin resistance is a pivotal feature in the pathogenesis of type 2 diabetes,
      and it may be detected 10-20 y before the clinical onset of hyperglycemia.
      Insulin resistance is due to the reduced ability of peripheral target tissues to
      respond properly to insulin stimulation. In particular, impaired insulin
      stimulated muscle glycogen synthesis plays a significant role in insulin
      resistance. Glucose transport (GLUT4), phosphorylation (hexokinase) and storage
      (glycogen synthase) are the three potential rate-controlling steps regulating
      insulin-stimulated muscle glucose metabolism, and all three have been implicated
      as being the major defects responsible for causing insulin resistance in patients
      with type 2 diabetes. Using (13)C/(31)P magnetic resonance spectroscopy (MRS), we
      demonstrate that a defect in insulin-stimulated muscle glucose transport activity
      is the rate-controlling defect. Using a similar (13)C/(31)P MRS approach, we have
      also demonstrated that fatty acids cause insulin resistance in humans due to a
      decrease in insulin-stimulated muscle glucose transport activity, which could be
      attributed to reduced insulin-stimulated IRS-1-associated phosphatidylinositol 3
      kinase activity, a required step in insulin-stimulated glucose transport into
      muscle. Furthermore, we have recently proposed that this defect in insulin
      stimulated muscle glucose transport activity may be due to the activation of a
      serine kinase cascade involving protein kinase C theta and IKK-beta, which are
      key downstream mediators of tissue inflammation. Finally, we propose that any
      perturbation that leads to an increase in intramyocellular lipid (fatty acid
      metabolites) content such as acquired or inherited defects in mitochondrial fatty
      acid oxidation, defects in adipocyte fat metabolism or simply increased fat
      delivery to muscle/liver due to increased energy intake will lead to insulin
      resistance through this final common pathway. Understanding these key cellular
      mechanisms of insulin resistance should help elucidate new targets for treating
      type 2 diabetes.

PMID- 14704737
TI  - Inflammatory mechanisms in diabetes: lessons from the beta-cell.
AB  - Inflammation plays an important role in the destruction of pancreatic islet beta
      cells that leads to type I diabetes. This involves infiltration of T-cells and
      macrophages into the islets and local production of inflammatory cytokines such
      as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and interferon
      (IFN)-gamma. Our laboratory has developed several strategies for protecting beta
      cells against oxidative stress and cytokine-induced cytotoxicity. These include a
      cytokine selection strategy that results in cell lines that are resistant to the
      combined effects of IL-1 beta+IFN-gamma. More recently, we have combined the
      cytokine selection procedure with overexpression of the antiapoptotic gene bcl-2,
      resulting in cell lines with greater resistance to oxidative stress and cytokine
      induced damage than achieved with either procedure alone. This article summarizes
      this work and the remarkably divergent mechanisms by which protection is achieved
      in the different model systems. We also discuss the potential relevance of
      insights gained from these approaches for enhancing islet cell survival and
      function in both major forms of diabetes.

PMID- 14704738
TI  - Role of PPARs in the regulation of obesity-related insulin sensitivity and
      inflammation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor isoforms
      with key roles in the regulation of lipid and glucose metabolism. Synthetic
      ligands for PPAR gamma (and PPAR alpha) have effects of promoting insulin
      sensitization in the context of obesity. Recent evidence suggests that activation
      of PPAR delta might produce similar effects. Both PPAR gamma and PPAR alpha have
      also been shown to produce selected anti-inflammatory effects and to reduce the
      progression of atherosclerosis in animals (alpha and gamma) or in humans (alpha).
      Mechanisms underlying insulin-sensitizing effects are complex. For PPAR gamma,
      direct effects on adipose tissue lipid metabolism with secondary benefits in
      liver and/or muscle (lipid levels and insulin signaling) have been implicated.
      For PPAR alpha, accelerated lipid catabolism may contribute to reduced muscle or
      liver 'steatosis'. Anti-inflammatory mechanisms as contributors to the beneficial
      metabolic effects of PPAR activation are also worth considering for the following
      reasons: (1) obesity and insulin resistance are associated with a proinflammatory
      milieu. (2) PPAR gamma has clear effects to oppose the effects of tumor necrosis
      factor-alpha (TNFalpha) in adipocytes. (3) effects of PPAR ligands on cytokine
      mediated signaling (eg via NF-kappa B) may be expected to enhance insulin action.
      (4) Adipose production of several molecules that are implicated as markers or
      mediators of inflammation is reduced. (5) In humans, treatment with either PPAR
      alpha or PPAR gamma agonists has been shown to reduce circulating levels of
      proteins that serve as markers of inflammation. (6) Adiponectin, a fat-derived
      circulating factor that has been implicated as having anti-inflammatory activity,
      is induced by PPAR gamma agonism.

PMID- 14704739
TI  - Inflammation and cardiovascular disease: is abdominal obesity the missing link?

PMID- 14704740
TI  - Adipose tissue, insulin action and vascular disease: inflammatory signals.
AB  - Insulin resistance, both in nondiabetic and diabetic subjects, is frequently
      associated with obesity, particularly an excess of central fat. Many of the
      features that have been ascribed to the metabolic or insulin-resistance syndrome
      are also more commonly found in obese subjects. These phenotypes include diabetic
      dyslipidaemia, elevation of levels of plasminogen activator inhibitor-1,
      microalbuminuria and endothelial dysfunction. More recently, features of acute
      phase activation and low-grade inflammation, including elevated levels of
      fibrinogen, C-reactive protein and interleukin-6, have been associated with
      (central) obesity. Adipose tissue generation of cytokines has been shown in vitro
      and in vivo, and a number of novel cytokine-like molecules, collectively termed
      adipocytokines, have been identified as adipocyte products. While several of
      these, such as tumour necrosis factor-alpha, may act predominantly in autocrine
      or paracrine fashion, others are released into the systemic circulation, acting
      as signalling molecules to remote tissues, including liver, skeletal muscle and
      endothelium. A clearer understanding of adipose tissue signalling, and its
      contribution to the state of low-grade inflammation of obesity, will require
      physiological, as well as cellular and molecular, studies.

PMID- 14704741
TI  - Emerging relationships of inflammation, cardiovascular disease and chronic
      diseases of aging.
AB  - The last 10 y have seen an enormous surge in research focused on inflammation and
      atherosclerotic heart disease. In parallel, inflammation (used as a term to
      represent a broad array of response systems) has become a topic of interest in a
      number of different areas of chronic disease including type II diabetes,
      cognitive decline and frailty, among others. These discoveries are opening up
      many new opportunities for risk assessment. For example, markers of inflammation
      such as C-reactive protein are becoming established as important additions in
      helping to define those at the greatest risk of progressive vascular disease.
      These discoveries are also important in the area of risk management. Older
      medications now in wide use are being found to have previously unknown anti
      inflammatory effects (eg, statins); these effects are now viewed as being
      important to the overall effectiveness of these compounds. In addition, the many
      different aspects of inflammation provide a wealth of targets for new
      therapeutics, which will be increasingly important as the population continues to
      age. Although daunting in complexity, studies on the relation of inflammation to
      disease have already proven useful, and hold promise for providing fundamental
      advances in both basic biology and clinical medicine.

PMID- 14704742
TI  - Macrophages, inflammation, and atherosclerosis.
AB  - The macrophage plays a diverse array of roles in atherogenesis and lipoprotein
      metabolism. The macrophage functions as a scavenger cell, an immune mediator
      cell, and as a source of chemotactic molecules and cytokines. Chemokines have
      been implicated in promoting migration of monocytes into the arterial intima.
      Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes bearing the
      chemokine receptor CCR-2. Macrophage expression of cyclooxygenase-2, a key enzyme
      in inflammation, promotes atherosclerotic lesion formation in low-density
      lipoprotein receptor (LDLR)-deficient mice. In the arterial intima, monocytes
      differentiate into macrophages, which accumulate cholesterol esters to form lipid
      laden foam cells. Foam cell formation can be viewed as an imbalance in
      cholesterol homeostasis. The uptake of atherogenic lipoproteins is mediated by
      scavenger receptors, including SR-A and CD36. In the macrophage, ACAT-1 is
      responsible for esterifying free cholesterol with fatty acids to form cholesterol
      esters. Surprisingly, deficiency of macrophage ACAT-1 promotes atherosclerosis in
      LDLR-deficient mice. A number of proteins have been implicated in the process of
      promoting the efflux of free cholesterol from the macrophage, including apoE,
      ABCA1, and SRB-1. Macrophage-derived foam cells express the adipocyte fatty acid
      binding protein (FABP), aP2, a cytoplasmic FABP that plays an important role in
      regulating systemic insulin resistance in the setting of obesity. ApoE-deficient
      mice null for macrophage aP2 expression develop significantly less
      atherosclerosis than controls wild type for macrophage aP2 expression. These
      results demonstrate a significant role for macrophage aP2 in the formation of
      atherosclerotic lesions independent of its role in systemic glucose and lipid
      metabolism. Furthermore, macrophages deficient in aP2 display alterations in
      inflammatory cytokine production. Through its distinct actions in adipocytes and
      macrophages, aP2 links features of the metabolic syndrome including insulin
      resistance, obesity, inflammation, and atherosclerosis.

PMID- 14704743
TI  - Peroxisome proliferator-activated receptors and inflammation: from basic science
      to clinical applications.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor family. After activation by specific ligands, they regulate the
      transcription of genes involved in lipid and lipoprotein metabolism, glucose and
      energy homeostasis, as well as cellular differentiation. Recent studies have
      identified expression of the three PPARs in all cells of the arterial wall, where
      they control cholesterol homeostasis as well as the inflammatory response and, as
      a consequence, modulate atherogenesis. More generally, PPARs influence cell
      proliferation as well as the immune and inflammatory response in different
      tissues and cells. In this review, we will summarize the evidence indicating that
      PPARs are modulators of the inflammatory response with potential therapeutic
      applications not only in atherosclerosis, but potentially also in other
      inflammation-related diseases, such as hepatic inflammation and inflammatory
      bowel disease.

PMID- 14704744
TI  - Molecular mechanisms of inflammation in obesity-linked insulin resistance.

PMID- 14704745
TI  - Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet
      induced insulin resistance.
AB  - Antidiabetic effects associated with salicylates have been known for years,
      although the underlying mechanisms were not understood. We have been
      reinvestigating these effects in the light of recent discoveries in the areas of
      signal transduction and insulin resistance. Our findings showed that signaling
      pathways leading to I kappa B kinase beta (IKK beta) and NF-kappa B are activated
      in insulin-responsive tissues of obese and high-fat-fed animals. Since activation
      correlates with the development of insulin resistance, we asked whether signaling
      through this might be involved in the pathogenesis of insulin resistance.
      Heterozygous gene deletion (Ikk beta+/-) or salicylates, working as IKK beta
      inhibitors, improved insulin sensitivity in insulin-resistant rodent models.
      Furthermore, high doses of salicylates (aspirin or salicylate) improved insulin
      sensitivity in patients with type II diabetes. Our studies implicate an
      inflammatory process in the pathogenesis of insulin resistance in obesity and
      type II diabetes mellitus and identify the IKK beta/NF-kappa B pathway as a
      molecular mediator of insulin resistance and pharmacological target for insulin
      sensitization.

PMID- 14704746
TI  - Inflammatory pathways and insulin action.
AB  - Obesity and type 2 diabetes are associated with a state of abnormal inflammatory
      response. While this correlation has also been recognized in the clinical
      setting, its molecular basis and physiological significance are not yet fully
      understood. Studies in recent years have provided important insights into this
      curious phenomenon. The state of chronic inflammation typical of obesity and type
      2 diabetes occurs at metabolically relevant sites, such as the liver, muscle, and
      most interestingly, adipose tissues. The biological relevance of the activation
      of inflammatory pathways became evident upon the demonstration that interference
      with these pathways improve or alleviate insulin resistance. The abnormal
      production of tumor necrosis factor alpha (TNF-alpha) in obesity is a paradigm
      for the metabolic significance of this inflammatory response. When TNF-alpha
      activity is blocked in obesity, either biochemically or genetically, the result
      is improved insulin sensitivity. Studies have since focused on the identification
      of additional inflammatory mediators critical in metabolic control and on
      understanding the molecular mechanisms by which inflammatory pathways are coupled
      to metabolic control. Recent years have seen a critical progress in this respect
      by the identification of several downstream mediators and signaling pathways,
      which provide the crosstalk between inflammatory and metabolic signaling. These
      include the discovery of c-Jun N-terminal kinase (JNK) and I kappa beta kinase (I
      kappa K) as critical regulators of insulin action activated by TNF-alpha and
      other inflammatory and stress signals, and the identification of potential
      targets. Here, the role of the JNK pathway in insulin receptor signaling, the
      impact of blocking this pathway in obesity and the mechanisms underlying JNK
      induced insulin resistance will be discussed.

PMID- 14704747
TI  - Role of Ser/Thr kinases in the uncoupling of insulin signaling.
AB  - Insulin resistance refers to a decreased capacity of circulating insulin to
      regulate nutrient metabolism. It is associated with the development of type II
      diabetes, a 21st century epidemic. Recent studies reveal that agents that induce
      insulin resistance exploit phosphorylation-based negative feedback control
      mechanisms otherwise utilized by insulin itself, to uncouple the insulin receptor
      from its downstream effectors and thereby terminate insulin signal transduction.
      This article focuses on the cardinal role of Ser/Thr protein kinases, which
      phosphorylate insulin receptor substrates, as key players in the uncoupling of
      insulin signaling and the induction of an insulin resistance state.

PMID- 14704748
TI  - Modulators of insulin action and their role in insulin resistance.
AB  - Insulin is a key anabolic hormone that plays a crucial role in growth,
      differentiation and metabolism. Insulin action is initiated by the binding of the
      hormone to its tyrosine kinase cell surface receptor, leading to the multisite
      autophosphorylation of the receptor. This results in the activation of the
      receptor kinase and subsequent tyrosine phosphorylation of insulin receptor
      substrates, most of which are docking proteins for signaling molecules. For the
      last several years, our laboratory has been interested in the mechanisms that
      lead to the modulation of insulin signal transduction, and hence might be
      involved in insulin resistance found in obesity and type II diabetes. For this
      review, we have focused on three 'modulators' of insulin action:
      hyperinsulinemia, suppressor of cytokine signaling proteins and advanced
      glycation end products.

PMID- 14704749
TI  - Ultrasonic localization of anaesthetic fluid using sub-Tenon's cannulae of three
      different lengths.
AB  - PURPOSE: To study the distribution of anaesthetic fluid during sub-Tenon's block
      by B-scan ultrasonography using cannulae of three different lengths. METHODS: A
      total of 30 patients undergoing routine phacoemulsification and lens implantation
      were studied after informed consent had been obtained. Ages ranged from 60 to 92
      years and globe axial lengths from 21.50 to 27.00 mm. All were given a sub
      Tenon's block and the patients were classified into three groups in which either
      a long, intermediate, or short cannula was used. B-scan ultrasonography was
      performed before administration of the anaesthetic agent, during injection, and 2
      min after completion of the injection. RESULTS: In all patients the optic nerve
      was identified. During the injection, anaesthetic fluid could be seen tracking
      behind the globe and opening up the posterior sub-Tenon's space (the previously
      described 'T'-sign). After 2 min very little or no fluid was seen, suggesting
      that it had dispersed into the surrounding tissues. There was no discernible
      difference in the distribution of fluid or in the quality of the block in the
      three groups. CONCLUSIONS: B-scan ultrasonography can reliably identify the
      distribution of anaesthetic fluid during sub-Tenon's block. Anaesthetic agents
      can be successfully delivered into the sub-Tenon's space by long, intermediate,
      or short cannulae.

PMID- 14704750
TI  - Open sky Muller's muscle-conjunctiva resection for ptosis surgery.
AB  - PURPOSE: We describe a surgical technique for ptosis correction in moderate to
      good levator function involving resection of Muller's muscle of the upper eyelid.
      This is a substantial modification of the technique described by Putterman. We
      then present our experience of and the results from this method. METHODS: A
      subtotal resection of Muller's muscle plus underlying conjunctiva is performed
      under direct visualisation. The muscle stump is reattached to the tarsus and the
      sutures passed through to the skin crease. In those cases where the phenylephrine
      test was positive to a level less than the desired lid height, a 1 mm of strip of
      tarsus is included in the tissue resection. The sutures are removed between 5
      days and 3 weeks postoperatively allowing control over lid height and contour. A
      total of 61 eyes of 48 patients underwent this procedure. RESULTS: Of 61 eyelids,
      56 undergoing this procedure were within 0.5 mm of the desired end point, giving
      a success rate of 92%. Of 61 eyelids, 60 were within 1 mm of the desired height.
      Preoperative phenylephrine 10% was highly predictive of postoperative lid height
      (58/61). An excellent lid contour was noted in all cases (61/61). CONCLUSIONS: We
      present a new approach to ptosis correction using Muller's muscle. It has a high
      success rate and good cosmetic outcome. It is technically straightforward and
      easy to learn.

PMID- 14704751
TI  - Unilateral inferior oblique muscle myectomy and recession in the treatment of
      inferior oblique muscle overaction: a longitudinal study.
AB  - BACKGROUND: The comparable long-term outcomes of inferior oblique muscle myectomy
      and recession for the treatment of superior oblique underaction (in primary
      position and straight right and left gaze) have not been well documented in the
      literature. The purpose of this study was to compare longitudinally these two
      procedures in a similar, patient population with binocular single vision, when
      both operations were performed by the same surgeon, with a minimum follow-up
      period of 12 months. METHODS: A total of 24 patients who randomly underwent
      either a unilateral myectomy (at the temporal border of the inferior rectus
      muscle) or a standard recession for inferior oblique muscle overaction associated
      with long-standing superior oblique underaction were evaluated preoperatively at
      2 weeks, 4 months, and 12 months postoperatively by the same orthoptist. RESULTS:
      A total of 23 patients met the study criteria, (12 myectomies and 11 recessions).
      All but one patient had demonstrable binocular single vision. The average
      preoperative hyperdeviation in contralateral gaze was 26.5 prism dioptres (Delta)
      in the myectomies and 20 Delta in the recessions. This was reduced at 12 months
      postoperatively to 1.75 Delta in the myectomies and to 3 Delta in the recessions.
      Both procedures were largely self-grading, so that the larger the preoperative
      hyperdeviation, the greater the effect of surgery. CONCLUSIONS: Single inferior
      oblique muscle-weakening procedures were effective in the vast majority of
      patients, even when the preoperative primary position hyperdeviation was 15 Delta
      or more. An improvement occurred in both groups immediately after surgery and in
      many throughout the follow-up period represented by a continuing drift towards
      orthotropia, but there was a recurrence of the hyperdeviation in some of the
      recession patients.

PMID- 14704752
TI  - Correlation between optic disc atrophy and aetiology: anterior ischaemic optic
      neuropathy vs optic neuritis.
AB  - BACKGROUND: The morphologic features of swollen disc in the acute stage of optic
      neuritis and anterior ischaemic optic neuropathy (AION) have been extensively
      investigated in contrast to the morphologic features of optic disc atrophy after
      these events. OBJECTIVE: : A prospective study to evaluate the morphologic
      features of optic disc atrophy 6 months or more after optic neuritis and
      nonarteritic AION. PATIENTS AND METHODS: A total of 35 optic discs after
      nonarteritic AION (n=27) and 24 after optic neuritis (n=19) in otherwise healthy
      subjects have been evaluated by direct fundoscopic examination with a +90
      diopters lens and optic disc photography. The average age of patients at the
      onset of AION was 57.8 years (range: 38-80) and at the onset of optic neuritis
      was 32.6 (range: 19-46). The female:male ratio was 18 : 17 in the former and 15 :
      9 in the latter. The evaluated parameters included: degree of rim pallor (0 to
      +3), location of rim pallor, height of rim above the retina, depth and width of
      cup, peripapillary retinal artery to vein (A : V) ratio, and peripapillary
      pigment epithelial atrophy. A comparison was made also with 17 age-matched normal
      discs of 17 patients. Statistical significance was calculated with chi(2) and
      Fisher's exact test. RESULTS: Most of the discs after AION were paler (+2: 70%,
      +3: 26%) than after optic neuritis (normal colour: 8%, +1: 58%, P< or =0.007).
      Rim segmental involvement after AION was usually either superior 'altitudinal'
      (53%) or inferior 'altitudinal' (29%), whereas after optic neuritis, it was
      usually either temporal-central (papillomacular) (42%) or diffuse temporal (42%,
      P<0.0001). Discs had lower A : V ratio (1 : 3, 40%) after AION compared with
      optic neuritis (1 : 3, 8%) (P=0.007). There were no significant differences
      between the two groups in height of the rim, cupping, and peripapillary atrophy.
      CONCLUSIONS: : A combination of the degree of rim pallor, location of rim pallor,
      and A : V ratio may be of value in assessing the aetiology of optic disc atrophy
      when no previous clinical data are available and a compressive lesion has been
      ruled out.

PMID- 14704753
TI  - Development and progression of cataract in patients required repeated corneal
      transplantation.
AB  - PURPOSE: To evaluate the incidence of cataract development in patients required
      repeated corneal transplantations, the types of cataract and the effect of
      cataract extraction on the corneal regrafts survival. PATIENTS AND METHODS: The
      charts of all the patients that underwent repeated corneal transplantation
      between 1985 and 1998 were reviewed for the development of cataract after the
      first or subsequent keratoplasties. In all, 80 patients underwent 122 repeated
      corneal transplantations, of which six underwent surgery in both eyes. The
      average follow-up period of all the patients with repeated keratoplasty was 89.5
      months from the first keratoplasty. RESULTS: Of 86 eyes 19 (22%) that underwent
      repeated keratoplasties developed cataract. The cataract developed between 1
      month and 17 years (average 61.3 months) after the first transplantation. The
      incidence of cataract development was independent of the number of repeated
      keratoplasties. In certain patients, such as patients with acute and severe
      regraft immune rejection, the cataract progressed more rapidly. Despite different
      cataract extraction procedures, the grafts in 17 eyes of the 19 (89.5%) failed
      following cataract surgery and 16 of them underwent additional corneal
      regrafting. The regrafts in eight of the 16 regrafted eyes (50%) remained clear
      with improvement in visual acuity. At the end of the follow-up, 10 eyes of the 19
      had clear regraft (53%) comparable with the rate of clear grafts in the entire
      regrafted group (51%, P=NS). CONCLUSION: Corneal transplantation may be a trigger
      for slow development of cataract over years but repeated keratoplasties did not
      increase the risk for cataract development. Although failure of regrafts may
      occur after cataract extraction, subsequent corneal transplantation has a
      comparable survival and visual outcome with the entire regrafted group.

PMID- 14704754
TI  - Orbital invasion by a pituitary macroadenoma without visual loss: case report and
      review of the literature.

PMID- 14704755
TI  - Vitreous cyst and a cataract in a toddler.

PMID- 14704756
TI  - Autosomal dominant retinitis pigmentosa in a five-generation pedigree in People's
      Republic of China.

PMID- 14704757
TI  - A case of inadvertent ocular perforation and intravitreal injection of
      depomedrone during peribulbar injection. Good visual prognosis with delayed
      vitrectomy.

PMID- 14704758
TI  - Dyskinetopsia during light adaptation associated with nefazodone treatment.

PMID- 14704763
TI  - Absence of COCH mutations in patients with Meniere disease.
AB  - Missense mutations in the coagulation factor C homology (COCH) gene (14q12-q13)
      cause the autosomal dominant sensorineural hearing loss and vestibular disorder
      DFNA9 (OMIM 603196), and a high prevalence of symptoms of Meniere disease (MD)
      has been described in families with a mutation in the COCH gene. In this study,
      we search for mutations in the COCH gene in peripheral blood from patients with
      definite MD. DNA was extracted from peripheral blood cells of 30 individuals with
      MD and 30 controls. Exons 4 and 5 of the COCH gene were amplified by PCR
      reaction, using primer pairs flanking both exons. Sequences were analysed by a
      DNA sequencing system and compared with the published COCH cDNA sequence. No
      differences were found in the nucleotide sequences of exons 4 and 5 in the COCH
      gene in patients with definite sporadic MD when they were compared with the
      control group. Patients with definite MD have a low prevalence of mutations in
      exons 4 and 5 of the COCH gene.

PMID- 14704765
TI  - Dendritic cells: emerging pharmacological targets of immunosuppressive drugs.
AB  - Immunosuppressive drugs have revolutionized organ transplantation and improved
      the therapeutic management of autoimmune diseases. The development of
      immunosuppressive drugs and understanding of their action traditionally has been
      focused on lymphocytes, but recent evidence indicates that these agents interfere
      with immune responses at the earliest stage, targeting key functions of dendritic
      cells (DCs). Here, we review our present understanding of how classical and new
      immunosuppressive agents interfere with DC development and function. This
      knowledge might provide a rational basis for the selection of immunosuppressive
      drugs in different clinical settings and for the generation of tolerogenic DCs in
      the laboratory.

PMID- 14704766
TI  - Lymphatic vasculature development.
AB  - Although the process of blood vasculature formation has been well documented,
      little is known about lymphatic vasculature development, despite its importance
      in normal and pathological conditions. The lack of specific lymphatic markers has
      hampered progress in this field. However, the recent identification of genes that
      participate in the formation of the lymphatic vasculature denotes the beginning
      of a new era in which better diagnoses and therapeutic treatment(s) of lymphatic
      disorders could become a reachable goal.

PMID- 14704767
TI  - Prevention of cervical cancer through papillomavirus vaccination.
AB  - A subset of human papillomaviruses (HPVs) promote anogenital malignancy,
      including cervical cancer, and prevention and treatment strategies that reflect
      the causal role of HPV are being developed. Vaccines based on HPV virus-like
      particles induce genotype-specific virus-neutralizing antibody and prevent
      infection with HPV. Persistent papillomavirus infection is required for the
      development of papillomavirus-associated cancer and, therefore, therapeutic
      vaccines are being developed to eliminate established papillomavirus infection.
      Such vaccines test principles for the growing field of tumour-antigen-specific
      immunotherapy. This article reviews progress in the field and draws conclusions
      for the development of future prophylactic and therapeutic viral vaccines.

PMID- 14704768
TI  - The human model: a genetic dissection of immunity to infection in natural
      conditions.
AB  - Tremendous progress has been achieved in developmental, cellular and molecular
      immunology in the past 20 years, largely due to studies using the mouse as a
      model system and the arrival of molecular genetics. Immunology is now faced with
      a difficult challenge. What are the functions of the individual cells and
      molecules in achieving immunity to infection? Renewed interest in animal models
      of disease has provided considerable insight in this area, but such models of
      infection suffer from the inherent limitation of being experimental. In humans,
      the complex host-environment interaction occurs in natural, as opposed to
      experimental, conditions. The human model is therefore an indispensable
      complement to animal models, as it allows an observational genetic dissection of
      immunity to infection.

PMID- 14704769
TI  - T-cell development made simple.
AB  - The thymus is the primary site of T-cell lymphopoiesis. However, the precise
      molecular interactions that enable the thymus to carry out this function are only
      recently being elucidated. Although several important molecular players have been
      identified, including soluble factors, extracellular matrix components, and
      integral membrane receptors and their ligands, the precise role of these
      molecules in thymocyte differentiation has yet to be fully characterized. In this
      regard, the advent of a simple and efficient culture system for the generation of
      T cells from stem cells, as discussed here, should greatly facilitate the study
      of T-cell development.

PMID- 14704770
TI  - Translational research in immunology: Japanese perspectives.
AB  - Japan has a formidable tradition in immunological research, starting with
      Shibasaburo Kitasato (1852-1931), who, after returning to Japan from his studies
      with Robert Koch, went on to build almost single-handedly a research tradition in
      investigative medical research, while engaging himself in the fight against
      infectious diseases. Over the past few decades, Japanese immunologists have been
      involved in many important discoveries at the forefront of immunological
      research, yet, when it comes to the translation of new discoveries into clinical
      innovations and new therapies, Japan's track record seems more modest.

PMID- 14704771
TI  - Wanted: career path for postdocs.

PMID- 14704772
TI  - Electrons in carbon country.

PMID- 14704774
TI  - Hydrogels: Wet or let die.

PMID- 14704775
TI  - Material witness: A matter of taste.

PMID- 14704776
TI  - Microfluidics: Sorting particles with light.

PMID- 14704778
TI  - Nanocrystalline metals: Mapping plasticity.

PMID- 14704779
TI  - Bioceramics: A concrete solution.

PMID- 14704780
TI  - Nanoporous glasses: Controlling crack propagation.

PMID- 14704781
TI  - Advanced anodes for high-temperature fuel cells.
AB  - Fuel cells will undoubtedly find widespread use in this new millennium in the
      conversion of chemical to electrical energy, as they offer very high efficiencies
      and have unique scalability in electricity-generation applications. The solid
      oxide fuel cell (SOFC) is one of the most exciting of these energy technologies;
      it is an all-ceramic device that operates at temperatures in the range 500-1,000
      degrees C. The SOFC offers certain advantages over lower temperature fuel cells,
      notably its ability to use carbon monoxide as a fuel rather than being poisoned
      by it, and the availability of high-grade exhaust heat for combined heat and
      power, or combined cycle gas-turbine applications. Although cost is clearly the
      most important barrier to widespread SOFC implementation, perhaps the most
      important technical barriers currently being addressed relate to the electrodes,
      particularly the fuel electrode or anode. In terms of mitigating global warming,
      the ability of the SOFC to use commonly available fuels at high efficiency,
      promises an effective and early reduction in carbon dioxide emissions, and hence
      is one of the lead new technologies for improving the environment. Here, we
      discuss recent developments of SOFC fuel electrodes that will enable the better
      use of readily available fuels.

PMID- 14704782
TI  - The zwitterion effect in high-conductivity polyelectrolyte materials.
AB  - The future of lithium metal batteries as a widespread, safe and reliable form of
      high-energy-density rechargeable battery depends on a significant advancement in
      the electrolyte material used in these devices. Molecular solvent-based
      electrolytes have been superceded by polymer electrolytes in some prototype
      devices, primarily in a drive to overcome leakage and flammability problems, but
      these often exhibit low ionic conductivity and prohibitively poor lithium-ion
      transport. To overcome this, it is necessary to encourage dissociation of the
      lithium ion from the anionic polymer backbone, ideally without the introduction
      of competing, mobile ionic species. Here we demonstrate the effect of
      zwitterionic compounds, where the cationic and anionic charges are immobilized on
      the same molecule, as extremely effective lithium ion 'dissociation enhancers'.
      The zwitterion produces electrolyte materials with conductivities up to seven
      times larger than the pure polyelectrolyte gels, a phenomenon that appears to be
      common to a number of different copolymer and solvent systems.

PMID- 14704783
TI  - Controlled assembly of dendrimer-like DNA.
AB  - DNA possesses many desirable chemical/physical properties as a polymeric
      material. With the myriad of tools available to manipulate DNA, there is great
      potential for using DNA as a generic instead of a genetic material. Although much
      progress has been made in DNA computing and DNA nanotechnology, the full
      achievement of DNA-based materials has not yet been realized. As almost all DNA
      molecules are either linear or circular, to rationally construct DNA materials
      one must first create additional shapes of DNA as basic building blocks. In
      addition, these DNA building blocks must be readily incorporated into larger
      structures in a controlled manner. Here, we show the controlled assembly of
      dendrimer-like DNA (DL-DNA) from Y-shaped DNA (Y-DNA). The synthesis of Y-DNA and
      controlled assembly of DL-DNA were robust and efficient; the resulting DL-DNA was
      stable and almost monodisperse. The multivalent DNA dendrimers can be either
      isotropic or anisotropic, providing great potential to link other entities.

PMID- 14704784
TI  - Deformation-mechanism map for nanocrystalline metals by molecular-dynamics
      simulation.
AB  - Molecular-dynamics simulations have recently been used to elucidate the
      transition with decreasing grain size from a dislocation-based to a grain
      boundary-based deformation mechanism in nanocrystalline f.c.c. metals. This
      transition in the deformation mechanism results in a maximum yield strength at a
      grain size (the 'strongest size') that depends strongly on the stacking-fault
      energy, the elastic properties of the metal, and the magnitude of the applied
      stress. Here, by exploring the role of the stacking-fault energy in this
      crossover, we elucidate how the size of the extended dislocations nucleated from
      the grain boundaries affects the mechanical behaviour. Building on the
      fundamental physics of deformation as exposed by these simulations, we propose a
      two-dimensional stress-grain size deformation-mechanism map for the mechanical
      behaviour of nanocrystalline f.c.c. metals at low temperature. The map captures
      this transition in both the deformation mechanism and the related mechanical
      behaviour with decreasing grain size, as well as its dependence on the stacking
      fault energy, the elastic properties of the material, and the applied stress
      level.

PMID- 14704785
TI  - Charge, orbital and spin ordering phenomena in the mixed valence manganite
      (NaMn3+(3))(Mn3+(2)Mn4+(2))O12.
AB  - Mixed-valence manganites with the ABO3 perovskite structure display a variety of
      magnetic and structural transitions, dramatic changes of electrical conductivity
      and magnetoresistance effects. The physical properties vary with the relative
      concentration of Mn3+ and Mn4+ in the octahedral corner-sharing network, and the
      proportion of these two cations is usually changed by doping the trivalent large
      A cation (for example, La3+) with divalent cations. As the dopant and the
      original cation have, in general, different sizes, and as they are distributed
      randomly in the structure, such systems are characterized by local distortions
      that make it difficult to obtain direct information about their crystallographic
      and physical properties. On the other hand, the double oxides of formula
      AA'3Mn4O12 contain a perovskite-like network of oxygen octahedra centred on the
      Mn cations, coupled with an ordered arrangement of the A and A' cations, whose
      valences control the proportion of Mn3+ and Mn4+ in the structure. The compound
      investigated in this work, (NaMn3+(3))(Mn3+(2)Mn4+(2))O12, contains an equal
      number of Mn3+ and Mn4+ in the octahedral sites. We show that the absence of
      disorder enables the unambiguous determination of symmetry, the direct
      observation of full, or nearly full, charge ordering of Mn3+ and Mn4+ in distinct
      crystallographic sites, and a nearly perfect orbital ordering of the Mn3+
      octahedra.

PMID- 14704786
TI  - Design and synthesis of self-ordered mesoporous nanocomposite through controlled
      in-situ crystallization.
AB  - Mesoporous materials are of technological interest because of their applications
      ranging from catalysts, molecular sieves, separation technology and gas sensors,
      to batteries and electronics. Here we demonstrate a synthetic methodology that
      allows us to create an ordered mesoporous nanocomposite with a crystalline oxide
      framework. We design a 'nanocrystal-glass' configuration to build a
      nanoarchitecture by means of surfactant-templated self-assembly followed by the
      controlled in-situ crystallization of materials. Functional nanocrystals are used
      as the building blocks of ordered mesopores, and the glass phase can act both as
      the 'glue' between nanocrystals and as a functionalized component in the
      composites. Specifically, we demonstrate this methodology for ordered mesoporous
      nanocomposites consisting of electrochemically active nanocrystals and
      semiconductive glass in the TiO2-P2O5-M(x)O(y) systems (where M is a metal ion).
      This approach could be applied to many other multicomponent oxides to fabricate
      mesoporous nanocomposites for numerous uses.

PMID- 14704788
TI  - Small world, big hopes.

PMID- 14704789
TI  - Expression profiling identifies the cytoskeletal organizer ezrin and the
      developmental homeoprotein Six-1 as key metastatic regulators.
AB  - Patients presenting with metastatic rhabdomyosarcoma (RMS), the most common soft
      tissue sarcoma in children, have a very poor clinical prognosis. This is due, in
      large part, to our rudimentary knowledge of the molecular events that dictate
      metastatic potential. We used cDNA microarray analysis of RMS cell lines, derived
      from Ink4a/Arf-deficient mice transgenic for hepatocyte growth factor/scatter
      factor (HGF/SF), to identify a set of genes whose expression was significantly
      different between highly and poorly metastatic cells. Subsequent in vivo
      functional studies revealed that the actin filament-plasma membrane linker ezrin
      (encoded by Vil2) and the homeodomain-containing transcription factor Six-1 (sine
      oculis-related homeobox-1 homolog) had essential roles in determining the
      metastatic fate of RMS cells. VIL2 and SIX1 expression was enhanced in human RMS
      tissue, significantly correlating with clinical stage. The identification of
      ezrin and Six-1 as critical regulators of metastasis in RMS provides new
      mechanistic and therapeutic insights into this pediatric cancer.

PMID- 14704790
TI  - PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.
AB  - Platelet-activating factor (PAF) induces pulmonary edema and has a key role in
      acute lung injury (ALI). Here we show that PAF induces pulmonary edema through
      two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and
      activation of the cyclooxygenase pathway. Agents that interfere with PAF-induced
      ceramide synthesis, such as steroids or the xanthogenate D609, attenuate
      pulmonary edema formation induced by PAF, endotoxin or acid instillation. Our
      results identify acid sphingomyelinase and ceramide as possible therapeutic
      targets in acute lung injury.

PMID- 14704791
TI  - The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.
AB  - Metastatic cancers, once established, are the primary cause of mortality
      associated with cancer. Previously, we used a genomic approach to identify
      metastasis-associated genes in cancer. From this genomic data, we selected ezrin
      for further study based on its role in physically and functionally connecting the
      actin cytoskeleton to the cell membrane. In a mouse model of osteosarcoma, a
      highly metastatic pediatric cancer, we found ezrin to be necessary for
      metastasis. By imaging metastatic cells in the lungs of mice, we showed that
      ezrin expression provided an early survival advantage for cancer cells that
      reached the lung. AKT and MAPK phosphorylation and activity were reduced when
      ezrin protein was suppressed. Ezrin-mediated early metastatic survival was
      partially dependent on activation of MAPK, but not AKT. To define the relevance
      of ezrin in the biology of metastasis, beyond the founding mouse model, we
      examined ezrin expression in dogs that naturally developed osteosarcoma. High
      ezrin expression in dog tumors was associated with early development of
      metastases. Consistent with this data, we found a significant association between
      high ezrin expression and poor outcome in pediatric osteosarcoma patients.

PMID- 14704793
TI  - N-domain-dependent nonphosphorylated STAT4 dimers required for cytokine-driven
      activation.
AB  - The N-terminal protein interaction domain (N-domain) of the signal transducer and
      activator of transcription-4 (STAT4) is believed to stabilize interactions
      between two phosphorylated STAT4 dimers to form STAT4 tetramers. Here, we show
      that nonphosphorylated STAT4 dimers form in vivo before cytokine receptor-driven
      activation. Mutations in the N-domain dimerization interface abolished assembly
      of nonphosphorylated STAT4 dimers and prevented STAT4 phosphorylation mediated by
      cytokine receptors. In addition, N-domain dimerization occurred for other STAT
      family members but was homotypic in character. This implies a conserved role for
      N-domain dimerization, which might include influencing interactions with cytokine
      receptors, favoring homodimer formation or accelerating formation of the
      phosphorylated STAT dimer.

PMID- 14704792
TI  - Priming of naive T cells inside tumors leads to eradication of established
      tumors.
AB  - The tumor barrier comprised of nonantigenic stromal cells may contribute to the
      failure of tumor rejection. The tumor-necrosis factor superfamily member LIGHT
      (also known as TNFSF-14) is a ligand of stromal cell-expressed lymphotoxin-beta
      receptor and T cell-expressed herpes viral entry mediator (HVEM). Here we show
      that forced expression of LIGHT in the tumor environment induces a massive
      infiltration of naive T lymphocytes that correlates with an upregulation of both
      chemokine production and expression of adhesion molecules. Activation of these
      infiltrating T cells, possibly through HVEM, leads to the rejection of
      established, highly progressive tumors at local and distal sites. Our study
      indicates that targeting the tumor barrier may be an effective strategy for
      cancer immunotherapy.

PMID- 14704794
TI  - IN MEMORIUM: Louis C. Lasagna, M.D., 1923-2003 American Journal of Therapeutics.

PMID- 14704795
TI  - Extracellular Na+ removal attenuates rundown of the epithelial Na+-channel (ENaC)
      by reducing the rate of channel retrieval.
AB  - Regulation of the epithelial sodium channel (ENaC) is important for the long-term
      control of arterial blood pressure as evidenced by gain of function mutations of
      ENaC causing Liddle's syndrome, a rare form of hereditary arterial hypertension.
      In Xenopus laevis oocytes expressing ENaC a spontaneous decline of ENaC currents
      over time, so-called rundown, is commonly observed. Mechanisms involved in
      rundown may be physiologically relevant and may be related to feedback regulation
      of ENaC by intra- or extracellular Na+. We tested the effect of extracellular Na+
      removal on ENaC rundown. Spontaneous rundown of ENaC was largely prevented by
      extracellular Na+ removal and was partially prevented by primaquine suggesting
      that it is due to endocytic channel retrieval. Liddle's syndrome mutation caused
      a reduced rate of rundown, and in oocytes expressing the mutated channel
      extracellular Na+ removal not only prevented rundown but even increased the ENaC
      currents (runup). Acute exposure to high extracellular Na+ drastically reduced
      whole-cell currents and surface expression of wild-type ENaC, while these effects
      were much smaller in ENaC with Liddle's syndrome mutation consistent with a
      stabilization of the mutated channel in the plasma membrane. Interestingly, the
      apparent intracellular Na+ concentration [Na+](i-app) was high (>60 mM) in ENaC
      expressing oocytes but rundown was not associated with a further increase in
      [Na+](i-app). We conclude that the inhibitory effect of extracellular Na+ removal
      on rundown is due to an inhibition of endocytic ENaC retrieval.

PMID- 14704796
TI  - GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre
      type-specific pattern.
AB  - Nine novel sugar transporter-like proteins have been discovered in the past 5
      years. The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11
      and GLUT12, have been detected in human skeletal muscle. In the present study, we
      examined the pattern of expression and localization of the GLUT isoforms 8, 11
      and 12 in human skeletal muscle using an immunohistochemical approach. Biopsies
      of human skeletal muscle from sedentary or trained healthy adults, from fetal
      muscle (24 weeks of gestation), from obese type-2 diabetic subjects, and from
      patients suffering from polymyositis or amyotrophic lateral sclerosis (ALS) were
      studied. GLUT8 and 12 immunoreactivity was below detection level in both
      developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present
      in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast,
      GLUT4 was expressed in all investigated muscle fibres, the pattern of expression
      of GLUT11 differs from that of GLUT4, suggesting a specialized function for
      GLUT11 with a regulation independent from that of GLUT4. Obesity, type-2
      diabetes, training, conditions of de- and reinnervation (ALS) and regeneration
      (polymyositis) failed to induce GLUT8 or -12 expression. Likewise, the fibre type
      dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow
      muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results
      indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed
      exclusively in slow-twitch muscle fibres and is unaffected by physiological and
      pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not
      appear to be of importance in human muscle under physiological and
      pathophysiological conditions.

PMID- 14704797
TI  - Extended left hepatectomy--modified operation planning based on three-dimensional
      visualization of liver anatomy.
AB  - BACKGROUND: Based on the patient history of a 62-year-old man with a centrally
      located hepatocellular carcinoma we describe the potential influence of three
      dimensional computed tomography (3D CT) on operation planning in extended left
      hepatectomy. METHOD AND RESULTS: By 3D reconstruction of the liver, not only
      variations of the intrahepatic vascular structure but also the number and extent
      of portal venous segments, as well as their relation to hepatic veins, can be
      visualized. Thus, areas at risk for either devascularization or venous congestion
      may be identified prior to liver resection. This is particularly important in
      extended hepatectomies with a small liver remnant, where already minor
      complications may have fatal consequences. CONCLUSION: In these resections,
      operation planning may be improved substantially by pre-operative 3D
      reconstruction.

PMID- 14704798
TI  - The influence of circulatory difference on muscle oxygenation and fatigue during
      intermittent static dorsiflexion.
AB  - This study aimed to examine the influences of circulatory difference on the
      utilization of O(2) and the progression of fatigue in the tibialis anterior (TA)
      muscle during dorsiflexion exercise, with reference to different body postures.
      The subjects performed intermittent static dorsiflexion at 50% of maximal
      voluntary contraction (MVC) up to exhaustion with the right leg either up or down
      relative to the heart. These exercises were performed with and without occluding
      muscle blood flow. Simultaneously with the surface electromyogram (EMG)
      measurement, total hemoglobin volume change and tissue oxygenation ( S(t)O(2)) of
      TA were measured using near-infrared spectroscopy (NIRS). When the subjects
      performed an exhaustive intermittent dorsiflexion exercise at 50% MVC, the
      endurance time decreased in the leg up position. Also, the progression of fatigue
      in TA detected using EMG signals (i.e. integrated EMG and mean power frequency of
      EMG) was faster with the leg elevated. The NIRS data indicated a lower blood
      volume and S(t)O(2) with the leg up than with the leg down during the exercise,
      which suggests that the deficit in the O(2) supply to exercising muscle's demand
      was more apparent in the leg up position. However, these differences in EMG and
      NIRS data disappeared when the blood flow was restricted in both positions. From
      these results it is concluded that the difference in exercising muscle
      oxygenation between two different body postures influenced the progression of
      muscle fatigue and caused the difference in endurance performance.

PMID- 14704799
TI  - Depth-related visually evoked potentials by dynamic random-dot stereograms in
      humans: negative correlation between the peaks elicited by convergent and
      divergent disparities.
AB  - Binocular visually evoked potentials (VEP) were recorded from the left and right
      occipital cortices of right-handed subjects in response to convergent and
      divergent stimuli, each having six disparity levels, using dynamic random-dot
      stereograms (DRDS). The VEP recorded consisted of a negative peak (N300) and a
      positive peak (P500) within intervals of 200-400 ms and 400-600 ms, respectively,
      with respect to the stimulus onset. For convergent disparities, the relationships
      between the amplitude of N300 and the degree of disparity showed convexity
      towards the disparity axis, whereas the same relationships displayed concavity
      for P500. For divergent disparities, on the other hand, the amplitude and the
      degree of disparity relationships showed concavity towards the disparity axis for
      N300, in contrast to those obtained by convergent disparities. Although the
      disparity profile of P500 displayed concavity in the left hemisphere, its right
      hemisphere counterpart turned out to be bi-modal in behaviour, indicating a
      relative loss of disparity sensitivity in the mid-disparity range. The
      significant negative correlation between the N300 and P500 behaviour in response
      to both stimulus modalities suggests that the activity of the N300 centre is
      effective in changing the synchronization level of the cell population comprising
      the P500 centre. The significant negative correlations between the profiles of
      the N300 wave in response to convergent DRDS and its divergent DRDS counterpart
      in both hemispheres, and between the profiles of the convergent and divergent
      P500 waves in the left hemisphere imply that the N300 and the P500 foci are
      sensitive to both the magnitude and the direction of the disparity. The latency
      differences between the two response modalities revealed that the N300 wave in
      response to convergent DRDS always led the N300 wave elicited by divergent DRDS,
      indicating that convergent disparities are processed faster than the divergent
      disparities.

PMID- 14704800
TI  - Leptin response to acute prolonged exercise after training in rowers.
AB  - The aim of this study was to determine if there is a training effect on leptin
      levels at rest or after prolonged exercise during an 8-month training season of
      rowers. Eleven trained rowers were evaluated at three sessions (control, early
      and late) during the season. At the early and late sessions, leptin and insulin
      concentrations were measured before and after 90 min of rowing exercise (70-75%
      maximal oxygen consumption, VO(2)max), 120 min and 24 h afterwards.
      Anthropometrics data were collected at each session. Energy balance was
      determined on the days of exercise sessions. Resting leptin levels were not
      modified over the season and were in correlation with weight and body fat
      (P<0.05). At exercise sessions, a delayed reducing effect of acute exercise on
      leptin levels appeared ( P<0.01 compared to pre-exercise). After 24 h of
      recovery, leptin levels remained lower at early (P<0.001) but not at late
      sessions, and a training effect appeared between early and late sessions
      (P<0.001). Leptin levels were correlated with energy balance at early and late
      sessions (P<0.05). At the two training sessions, insulin levels were decreased
      immediately post-exercise and at 120 min of recovery compared to pre-exercise
      (P<0.01 and P<0.001 respectively for the two sessions). A training effect on
      insulin levels appeared at 24 h of recovery (P<0.05 between early and late
      sessions). We concluded that rowing training over a season did not alter resting
      leptin levels but it attenuated the exercise-induced reduction in leptin. This
      could be attributed to an alteration in energy balance, although an influence of
      training on insulin may also be involved in the leptin response to acute
      exercise.

PMID- 14704801
TI  - Strength training effects on physical performance and serum hormones in young
      soccer players.
AB  - To determine the effects of simultaneous explosive strength and soccer training
      in young men, 8 experimental (S) and 11 control (C) players, aged 17.2 (0.6)
      years, were tested before and after an 11-week training period with respect to
      the load-vertical jumping curve [loads of 0-70 kg (counter-movement jump CMJ0
      70)], 5- and 15-m sprint performances, submaximal running endurance and basal
      serum concentrations of testosterone, free testosterone and cortisol. In the S
      group, the 11-week training resulted in significant increases in the low-force
      portion of the load-vertical jumping curve (5-14% in CMJ0-30, P<0.01) and in
      resting serum total testosterone concentrations (7.5%, P<0.05), whereas no
      changes were observed in sprint running performance, blood lactate during
      submaximal running, resting serum cortisol and resting serum free testosterone
      concentrations. In the C group, no changes were observed during the experimental
      period. In the S group, the changes in CMJ0 correlated ( P<0.05-0.01) with the
      changes in the 5-m ( r=0.86) and 15-m ( r=0.92) sprints, whereas the changes in
      CMJ40 correlated negatively with the changes in the testosterone:cortisol ratio (
      r=-0.84, -0.92, respectively, P<0.05). These data indicate that young trained
      soccer players with low initial strength levels can increase explosive strength
      by adding low-frequency, low-intensity explosive-type strength training. The
      inverse correlations observed between changes in CMJ40 and changes in the
      testosterone:cortisol ratio suggest that a transient drop in this ratio below 45%
      cannot always be interpreted as a sign of overstrain or neuroendocrine
      dysfunction.

PMID- 14704802
TI  - Erroneous identification in a mixed population: simulation using Israeli STR
      data.
AB  - Allele distributions of 10 short tandem repeat (STR) polymorphic DNA loci used in
      forensic and paternity testing were determined for a cohort comprising 163
      individuals representing a mixed Jewish Caucasian population. Typing was carried
      out by the commercial AmpF lSTR SGM Plus kit. The polymorphism and the utility of
      three of these markers for forensic studies in Israel were established for the
      first time. Results were compared with data for U.S. Caucasians and African
      Americans. The probability of identity of two persons of different ethnic origins
      for identification purposes is discussed. A lemma is presented to show that the
      chance of erroneous identification of an innocent person who belongs to a
      population that had not committed a crime will, in most cases, be smaller than
      for those who belong to a population that had truly committed the crime.

PMID- 14704804
TI  - Obstructive colitis proximal to partially obstructive colonic carcinoma: a case
      report and review of the literature.
AB  - BACKGROUND: Obstructive colitis refers to ulceroinflammatory lesions that occur
      in the colon proximal to an obstructing lesion. As this condition is not widely
      appreciated by pathologists or clinicians, we describe herein a case of colonic
      polyposis and sigmoid colonic carcinoma with obstructive colitis. PATIENT
      PRESENTATION: A 47-year-old Taiwanese woman presented to Cardinal Tien Hospital
      with a 3-day history of acute onset of abdominal pain, vomiting, and watery
      diarrhea. A lower gastrointestinal series using water-soluble contrast medium
      revealed annular narrowing of the sigmoid colon and showed polyposis at the
      rectosigmoid colon and regional colitis over the proximal descending colon. She
      was treated by total colectomy. Microscopic sections showed poorly differentiated
      adenocarcinoma, tubular adenomas, and a segment of obstructive colitis measuring
      25 cm in length 5 cm proximal to the colon tumor. The tumor was also retrieved
      for simultaneous analyses of replication error and loss of heterozygosity. A
      total of three instances of loss of heterozygosity were demonstrated at the P53,
      MET, and D8S254 gene loci. No examples of replication error were detected.
      CONCLUSION: Obstructive colitis can cause diagnostic and therapeutic problems.
      Colitis areas may be a source for septicemia or may perforate and lead to
      peritonitis. The frequently normal appearance at surgery may lead to involved
      segments of colon being used for anastomoses with consequent complications.
      Awareness of the features and incidence of obstructive colitis should help
      physicians avoid these diagnostic and therapeutic problems.

PMID- 14704805
TI  - Colonic anastomotic disruption in the immediate postoperative period.
AB  - BACKGROUND: Muscle relaxation is administered to patients undergoing laparotomy
      for colonic surgery. At the end of the procedure, relaxation needs to be reversed
      to facilitate extubation. This may be achieved by administering
      anticholinesterases such as neostigmine. PATIENT PRESENTATION: We present a case
      of colonic anastomotic dehiscence in the immediate postoperative period following
      the use of neostigmine to reverse intra-operative muscle relaxation. CONCLUSION:
      Neostigmine is frequently used to reverse muscle relaxation at the end of colonic
      surgery. However, the drug should be used with caution as it has been implicated
      as a cause of early anastomotic disruption.

PMID- 14704806
TI  - Choledochal cyst associated with portal hypertension.
AB  - Portal hypertension is a known complication of delayed presentation of
      choledochal cyst. In the literature, choledochal cyst presenting with portal
      hypertension has not been addressed adequately. The aetiology of portal
      hypertension in these cases has not been well studied, but it may be related to
      compression of the cyst over the portal vein, secondary biliary cirrhosis, or
      even extrahepatic portal venous thrombosis. We present our experience with four
      cases of choledochal cysts with associated portal hypertension over a 10-year
      period (1991-2001). Gastrointestinal bleeding, splenomegaly or incidental
      discovery of oesophageal varices led to the diagnosis of associated portal
      hypertension. Excision of choledochal cyst and bilioenteric bypass may not be
      feasible in those patients with massive collaterals in the region of porta with
      secondary portal hypertension. An initial approach of internal drainage
      (endoscopic/operative) of the cyst may allow regression of collaterals and
      subsequent safe excision of the cyst in this difficult group of patients. The
      liver function and histopathology dictated the final outcome.

PMID- 14704807
TI  - Kothari et al.: "An unusual cause of stridor: retropharyngeal cold abscess".

PMID- 14704809
TI  - Ileal atresia associated with a congenital vascular band anomaly: observations on
      pathogenesis.
AB  - We report the case of a newborn, who developed intestinal obstruction soon after
      birth. Exploratory laparotomy revealed a congenital vascular band anomaly
      extending from the antimesenteric border of the terminal ileum to the gallbladder
      in association with ileal atresia. Surgical intervention was performed for
      correction of the disorder. A review of the embryology and congenital vascular
      bands is presented together with discussion as to possible etiopathogenesis
      leading to small bowel atresia.

PMID- 14704811
TI  - Congenital cavernous angioma exhibits a progressive decrease in size after birth.
AB  - CASE REPORT: We report a case of congenital intracranial cavernous angioma, which
      was initially found at a gestational age of 34 weeks in utero as a mass lesion
      associated with hydrocephalus. After birth, the patient was treated for
      hydrocephalus first by external drainage and then by ventricular peritoneal
      shunt. The natural course of the mass lesion was observed until the age of 8
      months when the histopathological diagnosis confirmed the cavernous angioma after
      tissue was obtained by surgery. CT scans repeated monthly during this period
      demonstrated that the angioma continuously decreased in size. There was no
      evidence of hemorrhage in the angioma on serial CT scans. The histopathology
      revealed thrombosis of cavernous vessels with hyaloid changes in the angioma.
      DISCUSSION: The mechanisms of the decreasing size of the cavernous angioma have
      often been discussed in relation to spontaneous hemorrhages and resolution. The
      present case suggests a mechanism in which the spontaneous formation of a
      thrombus might be the dominant factor for the decrease in size. Thrombus
      formation may result from low perfusion due to the large size of the angioma.

PMID- 14704812
TI  - The prediction of postoperative hydrocephalus in patients with spina bifida.
AB  - OBJECT: The object was to derive a prediction rule for the development of
      postoperative hydrocephalus in patients with spina bifida by the measurement of
      cranial ventricular diameters using ultrasound. METHODS: Eighty-nine patients
      with spina bifida were studied prospectively. Each child had preoperative cranial
      ultrasound with measurement of the bifrontal diameter, bicaudate diameter and
      maximum transverse diameter of the body of the lateral ventricle by a single
      blinded observer. Repair of meningomyelocele was then undertaken and the patients
      followed up for development or progression of hydrocephalus. Logistic regression
      analysis determined the lowest values of the three cranial ventricular diameters
      associated with the maximum sensitivity and specificity for predicting
      postoperative hydrocephalus. These values were-bifrontal diameter >26 mm,
      bicaudate diameter >20 mm and body of lateral ventricle diameter >26 mm.
      CONCLUSIONS: It is possible to predict the development of postoperative
      hydrocephalus in patients with spina bifida by measuring cranial ventricular
      dimensions using preoperative ultrasound.

PMID- 14704813
TI  - Gliosarcoma occurring 8 years after treatment for a medulloblastoma.
AB  - CASE REPORT: We present a rare case of a gliosarcoma occurring 8 years following
      treatment for a medulloblastoma. The patient was diagnosed with a medulloblastoma
      at the age of 13 years. We considered the possibility of a radiation-induced
      tumour and present evidence supporting this view. The second cerebral tumour was
      excised and confirmed to be a gliosarcoma. The tumour bed was re-irradiated with
      three-dimensional conformal radiotherapy (3DCRT). She remained well for 6 months,
      after which there was clinicoradiological progression. CONCLUSIONS: During long
      term follow-up of patients with medulloblastomas, the possibility of radiation
      induced neoplasms must be borne in mind.

PMID- 14704814
TI  - [Tissue typing in perforating corneal transplantation].
AB  - The demand for matched corneal grafts has risen rapidly over the last years. One
      reason for this is the change in the judgement of the value of tissue and
      especially HLA typing for prevention of an immune reaction in perforating corneal
      transplantation. Besides HLA or major antigens, there are other immunologically
      relevant tissue surface molecules such as the non-MHC antigens of which blood
      groups and minor antigens are the most important. With regard to effective cost
      benefit and waiting time-benefit analyses, differentiated matching strategies are
      needed to assure optimized utilization and allocation of the still unsatisfactory
      number of available corneal grafts. With special matching strategies, such as the
      calculation of the individual waiting time, the consideration of split, non-MHC
      and HLA antigens, additional HLA loci as well as so-called "permissible" and
      "taboo" mismatches, much more has to be taken into account in the future than
      just the numerical correspondence of HLA antigens. This will make it possible to
      turn from a pure numerical approach to a functional matching strategy. This
      review summarizes the discussion and different matching strategies, possibilities
      and limitations of HLA and tissue typing in perforating corneal transplantation.

PMID- 14704815
TI  - [Current practice of immune prophylaxis and therapy in perforating keratoplasty.
      A survey of members of the Cornea Section of the German Ophthalmological
      Society].
AB  - PURPOSE: Different strategies are currently used for prophylaxis and therapy of
      immunological transplant reactions. The aim of the present study was to evaluate
      clinical practice in planning and treatment of perforating keratoplasty (KPL) in
      Germany. METHOD: A questionnaire was sent out to 148 members of the cornea
      section of the German Ophthalmological Society. The return consisted of 69 (47%)
      questionnaires representing 69% of institutions, 39% of responses returned from
      institutions performing <50 KPL/year, 15% from institutions operating >100 KPL
      and 4% from centres performing >300 KPL/year. RESULTS: Of the responders 13%
      currently never use HLA-matched grafts, 22% choose matched grafts in every risk
      KPL and 1.5% always use matched grafts. In normal risk situations 1.5% treat less
      than 2 weeks with topical steroids, 66% 3-12 months, 6.5% >1 year, 35%
      additionally treat with systemic steroids. Cyclosporine A (CsA) (92%) is besides
      steroids (80%) the most common systemic immunomodulatory agent in high risk
      situations, while methotrexate is used by only 9.5%. The duration of
      immunosuppressive therapy varies from <3 months (9%) up to >12 months (14%). The
      postoperative therapy after KPL in herpes includes topical (51%) and systemic
      aciclovir <3 (26%) and >3 weeks (67%) and additional systemic immunomodulatory
      agents (37%). The acute immune reaction is treated predominantly with steroids:
      topical (95%), subconjunctival (29%), intracameral (1.5%). Systemic steroids are
      given orally (48%) and intravenously (42%), 12% treat with topical CsA.
      CONCLUSIONS: Besides therapeutic options that are accepted as common practice
      (e.g. systemic CsA) clinical practice varies widely. This may reflect the lack of
      evidence-based clinical observations.

PMID- 14704817
TI  - [Siderosis bulbi. Is it still a problem?].
AB  - BACKGROUND: Siderosis bulbi (SB) is caused by un-removed intraocular iron
      containing foreign bodies. Our retrospective study was designed to establish the
      number of patients treated for SB at our ophthalmology department within the past
      10 years, and to find out why SB occurred. PATIENTS AND METHODS: Retrospectively,
      we analyzed the documentation of every patient treated at our department for
      ocular injury due to an intraocular metal foreign body between 1.1.1992 and
      1.1.2002. Particular attention was focussed on the documentation of patients
      exhibiting symptoms of SB. RESULTS: During this period of time, 48 eyes with an
      intraocular iron-containing foreign body were treated operatively. In 45 cases,
      the foreign body was removed within 3 days after injury without any symptoms of
      SB. Of these, three patients (6.2%) came so late for treatment that various
      clinical signs of SB were already present. CONCLUSIONS: There are three major
      reasons for the development of SB: some patients do not come for an examination
      because there is no discomfort, the second reason is that the medical treatment
      at the first visit was too superficial and thirdly a small foreign body may also
      be overlooked due to deficient or inappropriate methods of examination.
      Therefore, sporadic cases of SB are still to be expected in the future.

PMID- 14704816
TI  - [Immunomodulation in penetrating keratoplasty. Current status and perspectives].
AB  - The immune privileged nature of the cornea contributes to the favourable outcome
      in corneal grafts. However, preventive measures are necessary to reduce allograft
      rejection particular in "high-risk" cases. Although corticosteroids are still a
      major component of our immunopharmacological armentarium, they might be
      supplemented by other more specific immunomodulating agents. The spectrum
      includes agents such as azathioprin, methotrexate or more specific calcineurin
      inhibitors affecting T-cells (cyclosporin A, FK506) and highly selective
      monoclonal antibodies directed against T-cell subpopulations and other targets.
      In order to better evaluate the risks and benefit of these agents, the properties
      of established and forthcoming agents are presented. In addition, this review
      attempts to address some new concepts of tolerance induction following
      penetrating keratoplasty.

PMID- 14704819
TI  - [Quality of life and patient satisfaction after cataract surgery. Results of an
      observational study between 04/2001 and 06/2002].
AB  - BACKGROUND: Assessment of patient satisfaction and quality of life becomes
      increasingly important for the overall evaluation of therapy regimes. However, it
      is not certain whether standard quality of life questionnaires suffice to assess
      immediate changes in patient conditions such as induced by cataract surgery.
      METHODS: The increase in visual acuity was observed in 152 cataract patients as
      an objective efficacy parameter. In addition, subjective patient satisfaction and
      quality of life was obtained from these patients by means of a cataract-specific
      questionnaire 1 day before and 4 weeks after surgery. The questionnaire
      concentrates on the patients' overall flexibility and mobility, their estimation
      of medical and nursing care, changes in ophthalmological conditions and on
      complications after surgery. RESULTS: With an internal consistency of 82% the
      instrument can be regarded as moderately reliable but self-reported quality of
      life before surgery was found to be remarkably biased. None of the above quality
      of life determinants showed a clinically relevant correlation with the objective
      increase in visual acuity (absolute correlations <20%). Significant impact
      factors for overall quality of life satisfaction were the patients' overall
      flexibility ( p=0.049) and their estimation of medical and nursing care (
      p=0.027). CONCLUSIONS: Standard quality of life determinants provide independent
      subjective information in addition to the increase in visual acuity as an
      objective measure of clinical outcome. Overall assessment of patient satisfaction
      cannot be regarded as sufficient for the subjective evaluation of cataract
      surgery, since its estimation primarily depends on the patients' appreciation of
      medical and nursing care. An appropriately extensive means of quality of life
      assessment seems necessary and post-surgical data seems sufficient for the
      estimation of subjective therapy outcome measures in cataract patients.

PMID- 14704818
TI  - [Octreotide scintigraphy for the diagnosis of active Graves' ophthalmopathy].
AB  - PURPOSE: In this study the diagnostic accuracy of orbital octreotide uptake in
      patients with presumed active Grave's ophthalmopathy (GO) was evaluated. PATIENTS
      AND METHODS: A prospective study of 23 patients suffering from GO was carried
      out. Single photon emission computed tomography (SPECT) images were obtained 4 h
      after iv injection of 3 mCi 111 indium octreotide. The results were correlated
      with the patients clinical state during a follow-up of 17.5+/-6 months. RESULTS:
      Octreotide scintigraphy was positive in 15 and negative in 8 cases, 12 patients
      with positive octreotide scintigraphy underwent immunosuppressive treatment and
      showed a clinically positive response with regression of symptoms. In three cases
      the patients refused immunosuppressive treatment. Patients with negative
      pathologic orbital octreotide uptake did not undergo any treatment. CONCLUSION:
      Octreotide scintigraphy is a useful tool to determine the activity state of
      Graves' ophthalmopathy. Since Graves' ophthalmopathy must be treated in the
      active phase, octreotide scintigraphy should be performed in subacute cases to
      facilitate the indications for immunosuppressive treatment.

PMID- 14704820
TI  - [Prophylactic pan-coagulation from ischemic central vein occlusions?
      Practicability of the results from the Central Vein Occlusion Study Group].
AB  - PURPOSE: Central vein occlusions (CVO) with an avascular area of more than 10
      optic-disc areas are classified as ischemic by the Central Vein Occlusion Study
      Group (CVOSG). For patients without neovascularizations (NV) clinical controls
      every 4 weeks during the first 6 months are recommended instead of prophylactic
      pancoagulation (PC). In this study we examined the practicability of this
      recommendation. PATIENTS AND METHODS: We analysed the records of 15 patients with
      ischemic CVO and no clinical signs of NV and no prophylactic PC retrospectively.
      All these patients developed a neovascular glaucoma (NVG) despite using the
      criteria of the CVOSG and were then treated with cyclophotocoagulation (CPC).
      RESULTS: The time between first presentation and CPC was 4.4+/-2.9 months. Of
      these patients 7 developed a NVG within 4 weeks after initial presentation.
      CONCLUSIONS: This study shows that NV and NVG may develop much faster than 4
      weeks and can already be irreversible. Therefore it seems advisable to follow-up
      patients with increased risk factors even more frequently especially during the
      initial phase after CVO.

PMID- 14704821
TI  - [Influence of ciliary-retinal arteries on functional damage in open-angle
      glaucoma].
AB  - PURPOSE: The pattern of functional perimetric loss and morphologic neuroretinal
      rim loss in glaucoma depends on the localization of the central retinal vessel
      trunk in the lamina cribrosa. The purpose of the present study was to determine
      if the pattern of perimetric loss and rim loss are influenced by the presence and
      position of cilioretinal arteries. PATIENTS AND METHODS: Using automated
      perimetry and 15 degrees color stereo optic disc photographs of the optic disc,
      we compared 20 open-angle glaucoma patients exhibiting cilioretinal arteries in
      the temporal horizontal disc region with 70 open-angle glaucoma patients without
      cilioretinal arteries. RESULTS: Eyes with cilioretinal arteries and eyes without
      cilioretinal arteries did not differ significantly in global visual field indices
      nor in the mean defect for the central 10 degrees. No differences were detected
      for the areas of optic disc, neuroretinal rim, ratios of the temporal horizontal
      area-to-total area of rim and ratio of temporal horizontal rim area-to-nasal rim
      area. CONCLUSIONS: In contrast to the position of the central retinal vessel
      trunk, the presence and position of cilioretinal arteries do not markedly
      influence the pattern of glaucomatous damage.

PMID- 14704822
TI  - [Laser in situ keratomileusis for correction of hyperopia and hyperopic
      astigmatism using a scanning spot excimer laser. Results of a prospective
      clinical study after 1 year].
AB  - PURPOSE: The purpose of this investigation was to evaluate the safety, efficacy,
      predictability, stability and complications of LASIK for the treatment of
      hyperopia and hyperopic astigmatism using a scanning spot excimer laser. PATIENTS
      AND METHODS: A total of 64 consecutive LASIK operations (37 patients, mean age 41
      years, range 22-68 years) have been evaluated. The Hansatome microkeratome
      producing a superior hinge (flap diameter 9.5 mm) and a scanning spot excimer
      laser with an optical zone of 6.0 mm were used. Examinations were performed
      preoperatively, after 1 day, 7 days, 1 month, 4 and 12 months. RESULTS: One year
      after the primary procedure only 1 eye lost 2 or more lines of best-corrected
      visual acuity, 91% were within +/-1 line and 4 eyes gained 2 lines. Of these eyes
      50 (86%) reached an uncorrected visual acuity of > or=0.5, 32 (55%) > or=0.8, 16
      (28%) > or=1.0, 24 eyes (41%) needed a refractive correction of +/-0.5 D, 44 eyes
      (76%) of +/-1.0 D and 55 eyes (95%) of +/-2.0 D. The mean spherical equivalent
      after 1 year was +0.17+/-0.85 D. CONCLUSIONS: LASIK is suitable for the
      correction of hyperopia (up to a maximum of +5 D) and for hyperopic astigmatism
      (up to a maximum of -5 D). However, results were better in lower hyperopia (up to
      +3 D) than in the moderate hyperopia. The refractive results showed overall a
      good stability during the 12-month study period, but higher regression occurred
      in a few cases.

PMID- 14704823
TI  - [Long-term follow-up after autologous submandibular gland transplantation in
      scarring keratoconjunctivitis with absolute dry eyes].
AB  - INTRODUCTION: An autologous submandibular gland can be transplanted to the
      temporal fossa and following microvascular anastomosis to the temporal artery and
      vein and implantation of the secretory duct into the superotemporal conjunctival
      fornix to provide continuous substitute lubrication. Here we report our
      experiences with this procedure. PATIENTS AND METHODS: In a prospective,
      controlled clinical cohort study, we investigated the development of the Schirmer
      test, fluorescein-break up time (F-BUT), degree of discomfort, use of
      pharmaceutical tear substitutes, visual acuity, Rose Bengal staining and
      conjunctival hyperemia in 14 eyes with a successful submandibular gland
      transplant and 11 dry eyes without salivary lubrication. RESULTS: Over a mean
      postoperative period of 3.3 years the transplantation group showed significant
      improvements of the Schirmer-Test, FBUT, use of pharmaceutical tear substitutes,
      discomfort and Rose Bengal staining up to the last follow-up when compared to the
      preoperative and control groups. CONCLUSION: Transplantation of an autologous
      submandibular gland can improve the lubrication and discomfort of absolute tear
      deficiency on a long term basis, but the salivary tear film only partially
      stabilises the ocular surface. The procedure is however able to provide
      symptomatic relief in extreme cases of absolute dry eyes.

PMID- 14704824
TI  - [Readaptation time after photo-stress in normal subjects and glaucoma patients].
AB  - PURPOSE: A photo-stress test was conducted at the subjective contrast threshold
      to evaluate whether psychophysical differences could be detected between chronic
      open-angle glaucoma patients and normal subjects. METHODS: The prospective,
      comparative, clinical observational study included 20 patients (29 eyes) with
      chronic open-angle glaucoma and 20 control subjects (29 eyes). The study groups
      did not vary significantly in age and refractive error, but visual acuity showed
      a difference of 0.16. All participants underwent photo-stress using the
      Kontrastometer BA4. RESULTS: In the glaucoma group compared with the control
      group, the mean contrast threshold was significantly higher and the readaptation
      time significantly longer. The latter correlated significantly with the papillo
      morphological glaucoma stage. CONCLUSIONS: In patients with chronic open-angle
      glaucoma, the foveal recovery time after a photo-stress test is significantly
      prolonged compared with normal subjects. It may suggest involvement of the fovea
      in glaucoma even if the visual acuity is 20/20.

PMID- 14704826
TI  - [Acute vision loss].

PMID- 14704825
TI  - [Measuring patient's quality of life in ophthalmology].
AB  - BACKGROUND: The assessment of patient's quality of life is not only of vital
      importance for clinical trials of new therapies but also becomes more and more
      implemented into daily clinical therapeutical decisions. METHODS: Different
      methods for evaluating quality of life are available. A well-known questionnaire
      for measuring global quality of life is the Short Form 36 (SF 36). However, in
      ophthalmology more specific instruments for measuring visual quality of life are
      needed. We review the usefulness of specific questionnaires such as the Visual
      Function 14 (VF-14) or the National Eye Institute Visual Function Questionnaire
      (NEI-VFQ) in their application to common ophthalmologic diseases such as
      cataract, age-related macular degeneration and glaucoma. Studies applying these
      methods were identified by a search in the Medline database. RESULTS: Several
      instruments to measure visual life quality in ophthalmologic patients are
      available. Internal consistency and validity are shown. CONCLUSIONS: Evaluating
      visual quality of life is an important parameter for assessing ophthalmologic
      diseases and the value of different therapies. It is an important outcome
      variable in clinical studies. Furthermore, individual visual quality of life
      should be considered in individual therapeutic decisions and helps to assess the
      economic effect of current and new therapies.

PMID- 14704827
TI  - [Inferior retinal detachment with whitish subretinal lesion].

PMID- 14704828
TI  - [Bilateral uveitis intermedia. A 15-year clinical course].

PMID- 14704829
TI  - Phase II clinical trial of parenteral hydroxyurea in combination with
      fluorouracil, interferon and filgrastim in the treatment of advanced pancreatic,
      gastric and neuroendocrine tumors.
AB  - PURPOSE: Combined inhibition of ribonucleotide reductase (RR) and thymidylate
      synthase (TS), the enzymes responsible for a balanced supply of nucleotides for
      DNA synthesis, has been shown to induce synergistic antiproliferative effects in
      vitro. In the clinic, prolonged infusion of the RR inhibitor, hydroxyurea (HU),
      may be more effective than bolus or oral administration of drug. The purpose of
      the current study was to determine whether dose intensification of parenteral
      hydroxyurea in combination with fluorouracil could enhance the response rates of
      the combination against refractory upper gastrointestinal malignancies. METHODS:
      A clinical trial of parenteral, weekly, high-dose HU in combination with weekly,
      high-dose infusional fluorouracil (5FU) was initiated in patients with advanced
      pancreatic and gastric cancer. Patients received 5FU 1.3 g/m(2) by continuous
      intravenous infusion (CIVI) daily over 48 h weekly in combination with HU 4.3
      g/m(2) CIVI per day over 48 h weekly. Patients also received the biologic agent
      interferon alfa-2a 9 MU subcutaneously (s.c.) three times per week and filgrastim
      480 microg s.c. on days 3 (starting after midday), 4, 5, and 6 each week. Each
      cycle required treatment on days 1 and 8 every 22 days. RESULTS: Enrolled in the
      study were 32 patients, of whom 30 were evaluable. The median age was 56 years.
      Primary sites included pancreas (18), gastric (13) and islet cell (1). Despite
      filgrastim, the major toxicities were hematologic with 15 of 30 patients
      developing grade 3/4 granulocytopenia. Of the 30 patients, 4 developed grade 3/4
      diarrhea. Interferon-mediated fatigue was mild. Of 12 evaluable patients with
      gastric cancer, 1 had a partial response, and there were no responders among
      patients with pancreatic cancer. CONCLUSIONS: Combined inhibition of RR and TS
      using this high-dose, weekly, 48-h infusional regimen is not an improvement over
      single-agent therapy in these tumor types.

PMID- 14704830
TI  - The development of targeted chemotherapy for CNS lymphoma-a pilot study of the
      IDARAM regimen.
AB  - PURPOSE: We have developed and evaluated a CNS-targeted chemotherapy regimen
      based on the pharmacokinetic properties of the individual drugs in the
      combination. PATIENTS AND METHODS: In a twin-track study, 16 patients with
      secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were
      treated with IDARAM which comprised idarubicin 10 mg/m(2) i.v., days 1 and 2;
      dexamethasone 100 mg, 12-h infusion, days 1, 2 and 3; cytosine arabinoside (ARA
      C) 1.0 g/m(2), 1-h infusion, days 1 and 2; methotrexate 2.0 g/m(2), 6-h infusion,
      day 3 (with folinic acid rescue); and cytosine arabinoside 70 mg plus
      methotrexate 12 mg, intrathecally, days 1 and 8. Two cycles were delivered at 3
      weekly intervals. After response assessment, patients received adjuvant cranial
      radiotherapy (40 Gy over 20 fractions). RESULTS: The series comprised 24
      patients, 11 male and 13 female. Their median age was 53 years (range 21 to 73
      years). Grade 4 neutropenia and thrombocytopenia occurred in the majority of
      patients treated. Of the eight PCNSL patients, seven achieved complete remission
      (CR). Four remained in CR at the time of this report with a median duration of
      follow-up of 25 months (range 11 to 42 months). Of the 16 SCNSL patients, 12
      achieved CR. Seven patients remained in CR at the time of this report with a
      median duration of follow-up of 24 months (range 18 to 57 months). CONCLUSION:
      This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL
      and is suitable for further development and evaluation.

PMID- 14704831
TI  - 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine
      (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT)
      by electrophilic species generated by decomposition.
AB  - PURPOSE: To investigate the interaction of the electrophilic species generated by
      the decomposition of the antineoplastic prodrug 1,2-bis(methylsulfonyl)-1-(2
      chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M) on the ability of
      O(6)-alkylguanine-DNA alkyltransferase (AGT) to repair alkylated O(6)
      chloroethylguanine and/or N(1),O(6)-ethanoguanine DNA lesions. MATERIALS AND
      METHODS: The contributions of inhibitory electrophilic species generated from
      VNP40101M towards AGT was assessed using analogues that selectively generated
      either the chloroethylating or the carbamoylating components of VNP40101M. The
      activity of AGT was determined from the inhibition of crosslink formation from
      O(6)-chloroethylguanine and/or N(1),O(6)-ethanoguanine lesions. The half-lives of
      sulfonylhydrazine derivatives and isocyanates were measured using an
      acidification assay which gives a change in absorbance proportional to the
      release or consumption of small quantities of protons. RESULTS: Both of the
      reactive components produced by VNP40101M directly inactivated cloned human AGT;
      the carbamoylating moiety (IC(50) about 13 micro M) was approximately seven- to
      eight-fold more potent than the alkylating component(s) (IC(50) about 100 micro
      M). These inhibitory actions were moderated by the addition of naked T5
      bacteriophage DNA. Thus, AGT bound to DNA was markedly more resistant than free
      AGT to these electrophilic species. DNA also blocked the spontaneous loss of AGT
      activity which occurred upon incubation of this protein under mild conditions.
      CONCLUSIONS: The reaction of AGT with the methyl isocyanate generated from the
      decomposition of VNP40101M increased the net number of crosslinks generated by
      VNP40101M compared to a sulfonylhydrazine prodrug that formed the equivalent
      alkylating species in the absence of the cogeneration of methyl isocyanate. These
      actions may be of significance to the antineoplastic activity of VNP40101M.

PMID- 14704832
TI  - Monitoring tumor antigen specific T-cell responses in cancer patients and phase I
      clinical trials of peptide-based vaccination.
AB  - Numerous phase I and II clinical trials testing the safety and immunogenicity of
      various peptide vaccine formulations based on CTL-defined tumor antigens in
      cancer patients have been reported during the last 7 years. While specific T-cell
      responses can be detected in a variable fraction of immunized patients, an even
      smaller but significant fraction of these patients have objective tumor
      responses. Efficient therapeutic vaccination should aim at boosting naturally
      occurring antitumor T- and B-cell responses and at sustaining a large number of
      tumor antigen specific and fully functional effector T cells at tumor sites.
      Recent progress in our ability to quantitatively and qualitatively monitor tumor
      antigen specific CD8 T-cell responses will greatly help in making rapid progress
      in this field.

PMID- 14704833
TI  - Recombinant immunotoxins and retargeted killer cells: employing engineered
      antibody fragments for tumor-specific targeting of cytotoxic effectors.
AB  - Over the past years, monoclonal antibodies have attracted enormous interest as
      targeted therapeutics, and a number of such reagents are in clinical use.
      However, responses could not be achieved in all patients with tumors expressing
      high levels of the respective target antigens, suggesting that other factors such
      as limited recruitment of endogenous immune effector mechanisms can also
      influence treatment outcome. This justifies the search for alternative,
      potentially more effective reagents. Antibody-toxins and cytolytic effector cells
      genetically modified to carry antibody-based receptors on the surface, represent
      such tailor-made targeting vehicles with the potential of improved tumor
      localization and enhanced efficacy. In this way, advances in recombinant antibody
      technology have made it possible to circumvent problems inherent in chemical
      coupling of antibodies and toxins, and have allowed construction via gene fusion
      of recombinant molecules which combine antibody-mediated recognition of tumor
      cells with specific delivery of potent protein toxins of bacterial or plant
      origin. Likewise, recombinant antibody fragments provide the basis for the
      construction of chimeric antigen receptors that, upon expression in cytotoxic T
      lymphocytes (CTLs) or natural killer (NK) cells, link antibody-mediated
      recognition of tumor antigens with these effector cells' potent cytolytic
      activities, thereby making them promising cellular therapeutics for adoptive
      cancer therapy. Here, general principles for the derivation of cytotoxic proteins
      and effector cells with antibody-dependent tumor specificity are summarized, and
      current strategies to employ these molecules and cells for directed cancer
      therapy are discussed, focusing mainly on the tumor-associated antigens epidermal
      growth factor receptor (EGFR) and the closely related ErbB2 (HER2) as targets.

PMID- 14704835
TI  - Analysis of nitrated polycyclic aromatic hydrocarbons by liquid chromatography
      with fluorescence and mass spectrometry detection: air particulate matter, soot,
      and reaction product studies.
AB  - Polycyclic aromatic hydrocarbons (PAH) and their nitrated derivatives (nitro-PAH)
      are environmental pollutants which pose a threat to human health even at low
      concentration levels. In this study, efficient analytical methods for the
      analysis of nitro-PAH and PAH (extraction, clean-up, chromatographic separation,
      and spectrometric detection) have been developed, characterized, and applied to
      aerosol samples. The separation and quantification of 12 nitro-PAH was carried
      out by reversed-phase high performance liquid chromatography (HPLC), on-line
      reduction, and fluorescence detection. The detection limits were in the range of
      0.03-0.5 microg L(-1) (6-100 pg in the investigated sample aliquots), and the
      recovery rates from soot samples were 70-90%. Nitro-PAH and PAH concentrations
      have been determined for different types of soot and for urban, rural, and alpine
      fine air particulate matter (PM2.5). For the first time, trace amounts of nitro
      PAH have been detected in a high-alpine clean air environment. The on-line
      reduction and fluorescence technique has been complemented by atmospheric
      pressure chemical ionization time-of-flight mass spectrometry (APCI-TOF-MS). The
      MS detection allowed the analysis of partially nitrated and oxygenated PAH in
      laboratory studies of the heterogeneous reaction of PAH on soot and glass fiber
      substrates with gaseous nitrogen oxides and ozone. It led to the tentative
      identification of a previously unknown nitrated derivative of the particularly
      toxic PAH benzo[ a]pyrene (BaP-nitroquinone), and provides the first experimental
      evidence that PAH-nitroquinones can be formed by reaction of PAH with atmospheric
      photooxidants.

PMID- 14704834
TI  - Time course of clinical response to venlafaxine: relevance of plasma level and
      chirality.
AB  - OBJECTIVE: Early clinical response to antidepressant treatment is an important
      therapeutic goal, considering the psychological, social and economic consequences
      of depression. The aim of the present study was to investigate the relationship
      between the time course of response and the concentration of venlafaxine (V), its
      active metabolite O-desmethylvenlafaxine (ODV) and enantiomeric ratios V(+)/V(-)
      and ODV(+)/ODV(-). METHODS: Depressed inpatients ( n=35) received V orally at a
      fixed 300 mg daily dose. Accepted comedication included clorazepate (maximum 60
      mg/day), zopiclone (maximum 15 mg/day) and low-dose trazodone (maximum 200
      mg/day). Severity of depression was assessed on days 0, 4, 7, 11, 14, 21 and 28
      (Montgomery and Asberg Depression Rating Scale). Blood samples were taken on day
      14 and day 28 and submitted to stereoselective determination. All measurements
      reflected trough steady-state values. First, pattern analysis was used to provide
      a categorical perspective of clinical response (50% improvement from baseline
      depression score). Patients displaying non-response, transient response, early
      persistent response and delayed persistent response were compared with respect to
      racemic concentrations and enantiomeric ratios. Second, in a dimensional
      perspective, mixed-effects modelling was used to analyse severity of depression
      versus time curves with respect to the possible influence of concentrations and
      enantiomeric ratios. RESULTS: Comparison of patients with and without persistent
      response did not reveal any significant difference for V, ODV, V+ODV plasma
      levels or enantiomeric ratios. Persistent response was significantly associated
      with less frequent pre-study antidepressant medication and less frequent
      comedication with zopiclone (day 14) and clorazepate (day 28) during the study.
      Focus on patients with persistent response ( n=19, 54.3%) indicated that early
      response, first observed before day 14, was associated with significantly higher
      V+ODV concentration than delayed response (median 725 ng/ml versus 554 ng/ml,
      P=0.023). No difference was found for pre-study medication or comedication during
      the study. Shorter time to onset of response was significantly associated with
      lower V(+)/V(-) enantiomeric ratio (r(s)=0.48, P<0.05). Mixed-effects modelling
      of depression severity versus time curves in patients with persistent response
      confirmed that either higher V+ODV plasma level or lower V(+)/V(-) ratio were
      significantly associated with more rapid decrease of depression score (likelihood
      ratio tests, P=0.012 and P=0.046, respectively). CONCLUSION: Considering its
      modest sample size, naturalistic design and limited observation period, the
      present study provided preliminary indication that earlier clinical response may
      occur with higher V+ODV plasma level, extending previous dose-response studies.
      The hypothesis was also raised that exposure to a more potent noradrenergic
      therapeutic moiety, as reflected by a lower V(+)/V(-) ratio, may be relevant to
      early improvement of depression.

PMID- 14704836
TI  - Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic
      patients: the role of insulin resistance.
AB  - AIMS/HYPOTHESIS: This study was done to measure the effect of Na+ intake on blood
      pressure and albuminuria, in relation with insulin sensitivity and kidney
      haemodynamics, in Type 2 diabetic patients with and without microalbuminuria.
      METHODS: Type 2 diabetic patients, 20 with microalbuminuria, 21 without, spent
      two consecutive 7-day periods, one on a high (250 mmol), the other on a low-Na+
      (20 mmol) diet. Body weight, 24-h blood pressure and albuminuria were measured at
      the end of each period. At the end of high-Na+ diet insulin sensitivity
      (euglycaemic insulin clamp; 2 mU.kg(-1).min(-1)) and kidney haemodynamics were
      measured in nine patients from each group. RESULTS: Switching from low to high
      Na+ diet resulted in an increase in blood pressure (7.4+/-4.7 mmHg; p<0.001),
      body weight (1.9+/-0.4 kg; p<0.05) and albuminuria [from 80 (31-183) microg/min
      to 101 (27-965) microg/min; p<0.01) in patients with microalbuminuria. No changes
      occurred in patients without microalbuminuria. Patients with microalbuminuria
      also had greater intraglomerular pressure (44+/-1 mmHg vs 36+/-1; p<0.001),
      calculated from glomerular filtration rate, renal plasma flow, plasma protein
      concentration and the relationship between pressure and natriuresis. In these
      patients insulin sensitivity was lower (5.16+/-49 vs 7.36+/-0.63 mg.kg(-1).min(
      1); p=0.007). Urinary albumin excretion (r=0.40; p=0.009) and insulin sensitivity
      (r=-0.59; p=0.01) were correlated with intraglomerular pressure.
      CONCLUSION/INTERPRETATION: High salt intake increases blood pressure and
      albuminuria in Type 2 diabetic patients with microalbuminuria. These responses
      are associated with insulin resistance and increased glomerular pressure. Insulin
      resistance could contribute to greater salt sensitivity, increased glomerular
      pressure and albuminuria.

PMID- 14704839
TI  - Outcome of postoperative treatment for rectal cancer UICC stage II and III in day
      to-day clinical practice. Results from a retrospective quality control analysis
      in six institutions in North Bavaria (Germany).
AB  - BACKGROUND AND PURPOSE: Radiochemotherapy (RChT) as adjuvant treatment for rectal
      cancer UICC stage II/III has been recommended by the National Cancer Institute
      (NCI) since 1991 and in Germany since 1994. Quality and results of postoperative
      treatment in day-to-day clinical practice in a complete region are evaluated
      retrospectively in a multi-institutional approach. PATIENTS AND METHODS: 534
      patients from six institutions treated between 1993 and 1998 were evaluated. The
      institutions covered a complete region with radiotherapeutic care. Patients were
      staged as follows: UICC I 1%, II 28%, III 69%, and IV 2%. 92% received RChT, 8%
      radiotherapy (RT) alone. Median follow-up of patients was 47 months (17-91
      months). RESULTS: Only about 37% of expected patients were referred for
      postoperative treatment. The 5-year actuarial rate was as follows: local control
      75% (63-84%), freedom from distant metastases 56% (44-63%), disease-free survival
      (DFS) 53% (42-59%), and overall survival (OS) 53% (45-64%). In multivariate
      analysis, local control was significantly influenced by T- and N-category, tumor
      grading, and RChT instead of RT alone. 6% (2-11%) of patients showed involved
      resection margins, in 33% of patients categorized pN0 less than the required
      twelve lymph nodes were examined, both leading to a significant decrease of local
      control. CONCLUSION: While the quality of adjuvant treatment followed consensus
      guidelines, the number of referred patients which was lower as expected and the
      inferior treatment results as compared to randomized studies indicate that the
      consensus recommendations for adjuvant treatment have not been fully accepted.
      Instead of patient referral according to UICC stage, patient selection by the
      surgeons has been performed according to individual risk factors. Efforts have to
      be made not only to improve treatment results in randomized studies but also to
      transfer and control these standards in daily practice.

PMID- 14704837
TI  - Associations of measures of lung function with insulin resistance and Type 2
      diabetes: findings from the British Women's Heart and Health Study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the associations of lung
      function with insulin resistance and Type 2 diabetes. METHODS: We did a cross
      sectional study of 3911 women who were 60 to 79 years old from 23 British towns,
      assessing the association of measures of lung function with insulin resistance
      (based on fasting insulin and glucose concentrations) and Type 2 diabetes (World
      Health Organisation diagnostic criteria). RESULTS: Forced expiratory volume in 1
      second (FEV1) and forced vital capacity (FVC) were inversely associated with
      insulin resistance and prevalence of Type 2 diabetes. In age-adjusted analyses,
      the homeostasis model assessment (HOMA) score (insulin resistance) decreased by
      5% (95% CI: 2-7%) for a one standard deviation increase in log FEV1 and by 8%
      (95% CI: 6-10%) for a one standard deviation increase in log FVC. With additional
      adjustment for height, smoking, BMI, waist-to-hip ratio, physical activity, white
      cell count, adult social class, childhood social class and respiratory
      medication, these associations attenuated to 3% (95% CI: 1 to 5%) and 5% (95% CI:
      3 to 8%). The fully adjusted odds ratio for diabetes prevalence was 0.85 (95% CI:
      0.74-0.98) for a one standard deviation increase in log FEV1 and 0.80 (95% CI:
      0.70-0.92) for a one standard deviation increase in log FVC. Forced expiratory
      flow in the central period of FVC was not associated with insulin resistance or
      diabetes. CONCLUSIONS/INTERPRETATION: Lung function measures which predominantly
      reflect lung volume are inversely associated with insulin resistance and Type 2
      diabetes. These associations could reflect childhood exposures which affect lung
      growth and also programme insulin resistance.

PMID- 14704840
TI  - Recurrent rectal cancer within the pelvis. A multicenter analysis of 123 patients
      and recommendations for adjuvant radiotherapy.
AB  - BACKGROUND AND PURPOSE: Recommendations for radiation ports in adjuvant radiation
      therapy for rectal cancer are mainly based on analysis of recurrence patterns. To
      evaluate whether changes in surgical technique have influenced this pattern of
      recurrence, a multicenter retrospective analysis was carried out on a patient
      population treated recently. PATIENTS AND METHODS: 123 patients were evaluated
      with the help of a CT-based self-developed 3-D data file system and an extensive
      questionnaire. Major inclusion criteria (one sufficient) for eligibility were:
      histological confirmation, clear bone destruction, and a positive PET scan, or at
      least three minor criteria: progressive soft tissue mass, invasion of adjacent
      organs on follow-up CT or MRI, rising tumor markers, and typical appearance in
      cross-sectional imaging. Clinical or serologic signs of inflammation were
      exclusion criteria. RESULTS: Initially, 54% of the evaluated patients were N0; in
      the remainder, N1 and N2 were distributed evenly. Initial T-category was T1 in
      2%, T2 in 24%, T3 in 60%, and T4 in 13%, the male-to-female ratio was 2:1.
      Recurrent tumors were mainly situated in the posterior part of the bony pelvis as
      displayed in the figures. When abdominoperineal resection was compared to low
      anterior resection as primary operation, there was a significant difference in
      extension of recurrent tumors in the inferior parts of the pelvis (p<0.025 in all
      statistical tests applied), whereas no significant difference was found in the
      superior parts of the pelvis. CONCLUSION: Based on these results, a modest field
      size reduction in adjuvant radiotherapy for rectal cancer seems feasible,
      offering the perspective of a reduction in acute and late side effects.

PMID- 14704841
TI  - [Offsprings of preconceptionally irradiated parents. Final report of a
      longitudinal study 1976-1994 and recommendations for patients' advisory].
AB  - BACKGROUND: Many young adults with cancer of good prognosis seek advice from
      their doctors, because they are concerned about their ability to have children
      and about potential hereditary diseases in the children conceived or fathered
      after cancer therapy. PATIENTS AND METHODS: Results of repeated examinations of
      61 children over a period of 20 years are reported. One of their parents had
      received radiotherapy for malignant disease (only three had additional
      chemotherapy). Radiation doses to the gonads ranged from 0.01 to 2 Gy. The most
      frequent indications for radiotherapy were Hodgkin's disease (n=25), seminomas
      (n=7), thyroid cancer (n=3), and malignant melanomas (n=3) RESULTS: There was a
      trend to premature birth with 52.5% of the babies born before term. Yet, all had
      normal birth weight and delivery was inconspicuous. The skeletal maturation was
      retarded, but development was still in the normal range of German children. There
      were no chromosome aberrations, normal mental and intellectual development, and
      no malignancy among these children. A trend to an increased frequency of
      developmental disturbances and four moderately severe malformations were
      observed; however, no direct association with radiation treatment could be
      demonstrated. One child had a balanced translocation (5;17) which it inherited
      from the unirradiated parent. CONCLUSION: During the first consultation of young
      adult cancer patients, before the start of treatment, the problems of fertility
      and of therapy-induced mutations and hereditary diseases as well as developmental
      damage of the offspring need to be addressed directly by the radiation
      oncologist. Decisions on cryoconservation of sperm, fixation of the ovaries and
      dosimetry of the gonads during radiotherapy have to be made before the start of
      treatment. The rate of radiation-induced hereditary diseases and developmental
      damage in the children conceived or fathered after curative radiotherapy of one
      parent is estimated to increase by <0.1% (after gonadal exposure of 1 Gy).
      However, at present, heritable damage potentially induced by chemotherapy cannot
      be adequately quantified yet.

PMID- 14704842
TI  - Extracapsular extension in positive axillary lymph nodes in female breast cancer
      patients. Patterns of failure and indications for postoperative locoregional
      irradiation.
AB  - BACKGROUND AND PURPOSE: There has been little information regarding lymph node
      positive breast cancer patients with extracapsular extension (ECE). The aim of
      this study was to evaluate the role of ECE in predicting survival and relapse
      rates. PATIENTS AND METHODS: From 1994-2002, 1,078 lymph node-positive women with
      breast carcinoma were treated at our institution, whereas 301 patients (27.9%)
      presented with ECE. 91 patients (30.2%) were identified as having three or less
      lymph nodes involved, 27.9% patients four to six, 15.6% patients seven to nine,
      and 26.2% patients ten or more nodes, respectively. The median age was 58.4 years
      (range: 28-84 years) and the median follow-up 34 months (range: 2-99 months).
      Nodal irradiation was given to patients with four or more positive lymph nodes.
      Chemotherapy was administered to 69.8%, hormonal therapy to 53.2%, and combined
      systemic treatment to 26% of patients. RESULTS: The 1-, 3-, and 5-year overall
      survival (OS) was 98%, 84%, and 73%, the 1-, 3-, and 5-year disease-free survival
      (DFS) 95%, 69%, and 58%, and the 1-, 3-, and 5-year metastasis-free survival
      (MFS) 96%, 73%, and 60%. The relapse rates were 6.6% (local), 0.3%
      (supraclavicular), 0.7% (isolated axillary), 1% (local + axillary), and 0.7%
      (local + supraclavicular), respectively. 81 patients (27%) developed distant
      metastases. In December 2002, 245 patients (81.4%) were alive, 202/245 without
      progression, 32/245 with distant metastases, 5/245 with local/locoregional
      recurrence, and 6/245 patients with local and distant failure. CONCLUSION:
      Isolated axillary nodal failure remains low in lymph node-positive patients with
      ECE. Balancing the risks and benefits of irradiation, we continue to recommend
      that complete axillary irradiation is not routinely indicated after adequate
      axillary dissection.

PMID- 14704843
TI  - Local recurrence rates in breast cancer patients treated with intraoperative
      electron-boost radiotherapy versus postoperative external-beam electron-boost
      irradiation. A sequential intervention study.
AB  - BACKGROUND AND PURPOSE: The purpose of this sequential intervention study was to
      determine the rate of local recurrences and the rate of distant metastases in
      patients with invasive breast cancer who had been treated with breast-conserving
      surgery and postoperative radiation therapy to the whole breast either with
      postoperative electron boost in group 1 or with intraoperative electron boost
      (IORT) in group 2. PATIENTS AND METHODS: After breast-conserving surgery, 378
      women with invasive breast cancer of tumor sizes T1 and T2 received 51-56.1 Gy of
      postoperative radiation therapy to the whole breast in 1.7-Gy fractions. 188 of
      those patients additionally received a postoperative electron boost of 12 Gy in
      group 1 from January 1996 to October 1998. Consecutively, from October 1998 to
      March 2001, 190 patients received intraoperative electron-boost radiotherapy of 9
      Gy to the tumor bed in group 2. The groups were comparable with regard to age,
      menopausal status, tumor size, grading, and nodal status. All statistical tests
      were two-sided. RESULTS: During a median follow-up period of 55.3 months in group
      1 and 25.8 months in group 2, local recurrences were observed in eight of 188
      patients (4.3%) in group 1, and no local recurrence was seen in group 2
      (p=0.082). Distant metastases occurred in 15 of the 188 patients (7.9%) in group
      1 and in two of the 190 patients (1.1%) in group 2 (p=0.09). The 4-year actuarial
      rates of local recurrence were 4.3% (95% confidence interval, 1.8-8.2%) and 0.0%
      (95% confidence interval, 0.0-1.9%) and the 4-year actuarial rates of distant
      metastases were 7.9% (95% confidence interval, 4.5-12.8%) and 1.1% (95%
      confidence interval, 0.1-3.8%). CONCLUSION: Immediate IORT boost yielded
      excellent local control figures in this prospective investigation and appears to
      be superior to conventional postoperative boost in a short-term follow-up.

PMID- 14704844
TI  - Blood hemoglobin level and treatment outcome of early breast cancer.
AB  - BACKGROUND AND PURPOSE: To determine whether the blood hemoglobin concentration
      correlates with the prognosis of patients with early breast cancer and, if so,
      whether this is restricted to treatment modality. PATIENTS AND METHODS: Data were
      collected retrospectively from patients with early breast cancer (T1,2 N0-2 M0)
      who underwent either breast-conserving surgery followed by adjuvant radiotherapy
      (BCS-RT; n=96) or a modified radical mastectomy (MRM; n=194). The effect of
      preoperative blood hemoglobin level, nodal status, histological grading and
      hormone receptor status on disease-free survival was determined for both
      treatment modalities using a Cox regression model and visualized by Kaplan-Meier
      plots. RESULTS: The blood hemoglobin concentration significantly correlated with
      disease-free survival of patients receiving BCS-RT (relative risk [RR]: 0.67 per
      g/dl; p=0.007). This was independent of other known risk factors for breast
      cancer patients, as determined by multivariate analysis. By contrast, the blood
      hemoglobin level had no prognostic significance when patients were treated with
      MRM. CONCLUSION: Blood hemoglobin concentration seems to affect the prognosis of
      patients with early breast cancer when a treatment schedule that includes
      radiotherapy is applied. Reduced radiosensitivity due to diminished tumor
      oxygenation may be the underlying cause. Confirmative trials and studies intended
      to elucidate the underlying mechanism are warranted.

PMID- 14704845
TI  - Abrogation of radiation-inducible telomerase upregulation in HPV16 E6
      transfectants of human lymphoblasts.
AB  - BACKGROUND: Telomerase activity in a human lymphoblastoid cell line with wild
      type p53 status (TK6) was previously shown to be rapidly induced by ionizing
      radiation doses as low as 10 cGy. Since this low-dose response was absent in a
      closely related cell line overexpressing a mutant form of p53 (WTK1), the
      putative involvement of p53 was further investigated using stable human
      papillomavirus 16 (HPV16) E6 transfectants of these cell lines. The E6 product
      mediates rapid degradation of wild-type p53, but has also been found to
      upregulate telomerase. MATERIAL AND METHODS: Telomerase activity in HPV16 E6
      transfectants of the human lymphoblastoid cell lines TK6 and WTK1 was measured by
      PCR/ELISA and was quantified using internal standards (titration by cell number)
      run within each separate assay. Mean telomere length was determined by Southern
      hybridization of terminal restriction fragments with a biotin-labeled telomeric
      DNA probe. RESULTS: The TK6E6 and the WTK1E6 cells exhibited higher baseline
      telomerase activities than the parental cells. This was also accompanied by
      increased telomere lengths. Radiation exposure (up to 10 Gy) was unable to
      significantly further enhance telomerase activities, although the dynamic range
      of the assay would have allowed to record higher signals. CONCLUSION: The lacking
      radiation induction of telomerase activities in the E6 transfectants could
      reflect saturation, if E6 and radiation would share a common pathway of
      telomerase upregulation. Present evidence from the literature, however, suggests
      that E6 mediates telomerase reverse transcriptase (TERT) subunit transcriptional
      activation, whereas radiation signals to posttranscriptional/posttranslational
      control of telomerase activity. Therefore, the present data enforce the previous
      hypothesis of a p53 dependence of telomerase upregulation by low doses of
      radiation and its abrogation, likely due to p53 degradation, in E6-expressing
      cells.

PMID- 14704846
TI  - Study on the tongue and groove effect of the Elekta multileaf collimator using
      Monte Carlo simulation and film dosimetry.
AB  - BACKGROUND: Nowadays, multileaf collimation of the treatment fields from medical
      linear accelerators is a common option. Due to the design of the leaf sides, the
      tongue and groove effect occurs for certain multileaf collimator applications
      such as the abutment of fields where the beam edges are defined by the sides of
      the leaves. MATERIAL AND METHODS: In this study, the tongue and groove effect was
      measured for two pairs of irregular multileaf collimator fields that were matched
      along leaf sides in two steps. Measurements were made at 10 cm depth in a
      polystyrene phantom using Kodak EDR2 films for a photon beam energy of 6 MV on an
      Elekta Sli-plus accelerator. To verify the measurements, full Monte Carlo
      simulations were done. In the simulations, the design of the leaf sides was taken
      into account and one component module of BEAM code was modified to correctly
      simulate the Elekta multileaf collimator. RESULTS AND CONCLUSION: The results of
      measurements and simulations are in good agreement and within the tolerance of
      film dosimetry.

PMID- 14704847
TI  - In vivo verification of electron beam energy by patient exit dose and optical
      density of portal films.
AB  - BACKGROUND AND PURPOSE: The depth-dose curve of electron beams is mainly
      determined by their energy. For accelerators with scatter foils, the electron
      energy can, in principle, be verified by measuring the amount of the
      contaminating photons. This paper investigates whether exit dose measurements and
      evaluations of the optical density of portal films can be used to verify the
      energy of the electron beam in a clinically relevant setting. MATERIAL AND
      METHODS: During irradiation of the head and neck region of an Alderson-Rando
      phantom with 6- to 21-MeV electron beams, the exit dose rates behind the phantom
      and the dose rates at the position of a film cassette were measured. The optical
      density of films (EC film/EC-L Regular and EC-L Fast cassettes, Eastman Kodak
      Comp., Rochester, NY, USA) exposed to beams of different energies was evaluated.
      RESULTS: The exit and the cassette dose rates showed a steep increase with
      increasing electron energy. Due to its density behavior, the film with both types
      of cassettes failed to generate images for lower electron energies (6 and 9 MeV)
      but presented a strong ascent of the optical density-until reaching the
      saturation-with increasing electron energy. CONCLUSION: Measurements of the exit
      dose and evaluations of the optical density of portal films can be used to verify
      and document the energy of electron beams during radiotherapy.

PMID- 14704848
TI  - I was lucky, I was there at the right time.

PMID- 14704849
TI  - Retention of atherogenic lipoproteins in atherogenesis.
AB  - Atherosclerosis is a multifactorial disease whose pathogenesis is still unclear.
      Mounting evidence, however, supports the concept that subendothelial retention of
      apoB100-containing lipoproteins is the initiating event in atherogenesis.
      Subsequently, a series of biological responses to this retained material leads to
      specific molecular and cellular processes that promote lesion formation.

PMID- 14704850
TI  - Molecular neurophysiology of taste in Drosophila.
AB  - The recent identification of candidate receptor genes for sweet, umami and bitter
      taste in mammals has opened a door to elucidate the molecular and neuronal
      mechanisms of taste. Drosophila provides a suitable system to study the
      molecular, physiological and behavioral aspects of taste, as sophisticated
      molecular genetic techniques can be applied. A gene family for putative gustatory
      receptors has been found in the Drosophila genome. We discuss here current
      knowledge of the gustatory physiology of Drosophila. Taste cells in insects are
      primary sensory neurons whereupon each receptor neuron responds to either sugar,
      salt or water. We found that particular tarsal gustatory sensilla respond to
      bitter compounds. Electrophysiological studies indicate that gustatory sensilla
      on the labellum and tarsi are heterogeneous in terms of their taste sensitivity.
      Determination of the molecular bases for this heterogeneity could lead to an
      understanding of how the sensory information is processed in the brain and how
      this in turn is linked to behavior.

PMID- 14704851
TI  - Enzymology of NAD+ homeostasis in man.
AB  - This review describes the enzymes involved in human pyridine nucleotide
      metabolism starting with a detailed consideration of their major kinetic,
      molecular and structural properties. The presentation encompasses all the
      reactions starting from the de novo pyridine ring formation and leading to
      nicotinamide adenine dinucleotide (NAD(+)) synthesis and utilization. The
      regulation of NAD(+) homeostasis with respect to the physiological role played by
      the enzymes both utilizing NAD(+) through the nonredox NAD(+)-dependent reactions
      and catalyzing the recycling of the common product, nicotinamide, is discussed.
      The salient features of other enzymes such as NAD(+) pyrophosphatase,
      nicotinamide mononucleotide 5'-nucleotidase, nicotinamide riboside kinase and
      nicotinamide riboside phosphorylase, described under 'miscellaneous', are
      likewise presented.

PMID- 14704852
TI  - Neurotrophins and their receptors: signaling trios in complex biological systems.
AB  - The neurotrophins, a class of four related growth factors, utilize a dual
      receptor system consisting of Trk receptor tyrosine kinases and the structurally
      unrelated p75(NTR) to modulate diverse and sometimes opposing biological actions.
      The identification of novel ligands for p75(NTR), unconventional mechanisms for
      Trk activation and unique signaling intermediates further underscores the complex
      nature of neurotrophin: receptor interactions, as well as their functions within
      and outside of the nervous systems. This review summarizes recent surprises of
      how ligand-receptor pairing may affect diverse developmental events, regulate
      response to injury and extend their influence on memory and learning.

PMID- 14704853
TI  - Overview of mammalian zinc transporters.
AB  - In recent years, a number of mammalian zinc transporters have been identified,
      and candidate genes are rapidly growing. These transporters are classified into
      two families: ZIP (ZRT, IRT-like protein) and CDF (cation diffusion facilitator).
      ZIP members facilitate zinc influx into the cytosol, while CDF members facilitate
      its efflux from the cytosol. Molecular characterization of the transporters has
      brought about major advances in our understanding of their physiological
      functions. Zinc metabolism is regulated primarily through zinc-dependent control
      of transcription, translation, and intracellular trafficking of transporters.
      Analyses of mice whose zinc transporter genes have been genetically disrupted and
      of the naturally occurring mutant mice with symptoms related to abnormal zinc
      metabolism have provided compelling evidence that some zinc transporters play
      critical roles in zinc homeostasis. In this review, we review the literature of
      mammalian zinc transporters with emphasis on very recent findings and elicit
      integrative knowledge of zinc homeostasis.

PMID- 14704854
TI  - Wnt-frizzled signaling to G-protein-coupled effectors.
AB  - Wnt proteins signal via cell surface receptors termed Frizzleds. Frizzleds
      display many properties characteristic of members of the superfamily of G-protein
      coupled receptors, including heptihelical hydropathy plots; an exofacial N
      terminal region that is glycosylated; a cytoplasmic C-terminal region that
      includes canonical motifs for phosphorylation by protein kinase A, protein kinase
      C and casein kinase II; cytoplasmic domains that couple to heterotrimeric G
      proteins, as evidenced by a GTP-shift in receptor affinity; receptor-mediated
      responses sensitive to depletion of specific G protein subunits and receptor
      mediated responses sensitive to bacterial toxins that target G proteins. Evidence
      from a variety of developmental systems demonstrates Wnt-Frizzled (Fz) signaling
      via pathways other than the Wnt/beta-catenin pathway linked to transcription
      controlled by Lef/Tcf. Prominent among these additional pathways is a Wnt-Fz
      pathway regulating intracellular [Ca(++)] and cyclic GMP levels. The essential
      role of heterotrimeric G proteins in Wnt-Fz signaling is highlighted.

PMID- 14704855
TI  - Hypoxia and estrogen receptor profile influence the responsiveness of human
      breast cancer cells to estradiol and antiestrogens.
AB  - Angiogenesis activation mediated by vascular endothelial growth factor (VEGF) is
      one of the factors that can cause antiestrogen treatment failure in estrogen
      receptor (ER)?positive breast cancer patients. Since VEGF synthesis is modulated
      not only by hypoxia but also by steroid hormones, we investigated the
      relationship between hypoxic and estrogenic/antiestrogenic stimuli in two human
      breast cancer cell lines expressing both ER6alpha and ERbeta (MCF7) or only
      ERbeta (MDA-MB231). In both cell lines, the VEGF level was significantly
      influenced by hypoxic conditions and in antiestrogen-responsive MCF7 cells, this
      effect was not counteracted by tamoxifen or ICI 182780, thus providing an
      experimental explanation for the resistance to endocrine treatment observed in
      patients with ER-positive tumors. In MDA-MB231 cells, estradiol significantly
      reduced the VEGF level, suggesting that through the ERbeta isoform it may
      function as a negative modulator of VEGF synthesis under hypoxia, and providing
      evidence for a complex interplay of the estrogen-dependent and hypoxia-dependent
      pathways.

PMID- 14704856
TI  - Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB
      epithelial cells.
AB  - Betel quid (BQ) chewing shows a strong correlation to the incidence of oral
      submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca
      nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB).
      Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and
      IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell
      cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA
      synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show
      cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC
      induced apoptosis and cell cycle arrest are associated with mitochondrial
      membrane potential (delta Psim) depolarization as revealed by a decrease in
      rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100
      U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH
      depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen
      species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest
      and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10
      phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on
      HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at
      moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM,
      inhibitory effects were noted. These results indicate that HC consumption may be
      associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS
      production, mitochondrial dysfunction, cell cycle disturbance and the induction
      of apoptosis. These events are related to the production of superoxide radicals
      and hydrogen peroxide.

PMID- 14704857
TI  - Horizontal gene transfer from Eukarya to bacteria and domain shuffling: the alpha
      amylase model.
AB  - Alpha-amylases are present in all kingdoms of the living world. Despite strong
      conservation of the tertiary structure, only a few amino acids are conserved in
      interkingdom comparisons. Animal alpha-amylases are characterized by several
      typical motifs and biochemical properties. A few cases of such alpha-amylases
      have been previously reported in some eubacterial species. We screened the
      bacterial genomes available in the sequence databases for new occurrences of
      animal-like alpha-amylases. Three novel cases were found, which belong to
      unrelated bacterial phyla: Chloroflexus aurantiacus, Microbulbifer degradans, and
      Thermobifida fusca. All the animal-like alpha-amylases in Bacteria probably
      result from repeated horizontal gene transfer from animals. The M. degradans
      genome also contains bacterial-type and plant-type alpha-amylases in addition to
      the animal-type one. Thus, this species exhibits alpha-amylases of animal, plant,
      and bacterial origins. Moreover, the similarities in the extra C-terminal domains
      (different from both the alpha-amylase domain C and the starch-binding domain),
      when present, also suggest interkingdom as well as intragenomic shuffling.

PMID- 14704858
TI  - Unique evolution of Bivalvia arginine kinases.
AB  - The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of
      arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain
      structure, a result of gene duplication and subsequent fusion. These AKs also
      lack two functionally important amino acid residues, Asp(62) and Arg(193), which
      are strictly conserved in other 40-kDa AKs and are assumed to be key residues for
      stabilizing the substrate-bound structure. However, these AKs show higher enzyme
      activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam
      Scapharca broughtonii and the oyster Crassostrea gigas were determined. While
      Asp(62) and Arg(193) are conserved in Scapharca AK, these two key residues are
      replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from
      Crassostrea and both of the recombinant enzymes show an enzyme activity similar
      to that of two-domain clam AKs and at least twofold higher than that of other
      molluskan AKs. Although the replacement of Asp(62) or Arg(193) by Gly in normal
      AK causes a considerable decrease in V(max) (6-15% of wild-type enzyme) and a two
      to threefold increase in K(m) for arginine, the same replacement in Scapharca AK
      had no pronounced effect on enzyme activity. Together with the observation that
      bivalve AKs are phylogenetically distinct from other molluskan AKs, these results
      suggest that bivalve AKs have undergone a unique molecular evolution; the
      characteristic stabilizing function of residues 62 and 193 has been lost and,
      consequently, the enzyme shows higher activity than normal.

PMID- 14704859
TI  - The Ets-1 transcription factor is involved in the development and invasion of
      malignant melanoma.
AB  - The Ets-1 transcription factor plays a role in tumor vascularization and invasion
      by regulating expression of matrix-degrading proteases in endothelial cells and
      fibroblasts in the tumor stroma. During early embryogenesis, Ets-1 is expressed
      in migrating neural crest cells from which melanocytes arise. In the present
      study, we analyzed Ets-1 expression in various melanocytic lesions and
      investigated its functional importance in malignant melanomas. We found that Ets
      1 was upregulated both in vivo and in vitro in malignant melanoma, compared to
      benign melanocytic lesions and to primary melanocytes. Assessment of DNA-binding
      and transactivation assays documented a strong Ets activity in melanoma cells.
      Using an antisense strategy, the expression and activity of Ets-1 were reduced in
      the melanoma cell line Mel Im. This correlated with a diminished expression of
      several Ets-1 target genes known to be involved in invasion, such as MMP1, MMP3,
      uPA and integrin beta3. In line with these findings, the invasive potential of
      the melanoma cells measured in a Boyden Chamber model was reduced up to 60% after
      Ets-1 blockade. This can be attributed to the role of Ets-1 in transcriptional
      regulation of factors involved in invasion of melanoma cells. We conclude that
      over-expression of Ets-1 during melanoma development contributes to the malignant
      phenotype.

PMID- 14704862
TI  - Pathogenesis of angiopathy in diabetes.
AB  - Hyperglycaemia as a common feature of diabetes mellitus is a cause of different
      pathogenic mechanisms influencing endothelial function. Oxidative stress is one
      of the main causative factors inducing endothelial dysfunction and changes in
      plasma protein or platelet function. In type 2 diabetes mellitus, a combination
      of hyperglycaemia together with dyslipidaemia, obesity and other factors may
      accelerate the process of glycoxidation and lipid oxidation, causing an early
      impairment of the vessel wall or properties of circulating blood. This induces
      hypercoagulability characterised by impaired fibrinolysis and hyperaggregability.
      The initial functional changes are later substituted by morphologically impaired
      structure of the blood capillaries (microangiopathy) or arteries
      (macroangiopathy). The latter represent advanced atherosclerosis when typical
      plaques are formed. Failure of protective scavenger mechanisms is one possible
      explanation of vessel wall pathology in diabetes.

PMID- 14704860
TI  - Two-staged operation on C2 neoplastic lesions: anterior excision and posterior
      stabilization.
AB  - This retrospective study included eight consecutive cases with C2 vertebral body
      neoplastic lesions. The anterior retropharyngeal approach was used to remove the
      lesions and decompress the spinal cord. Spinal stabilization with
      occipitocervical plating in a second-stage operation makes the treatment more
      tolerable for patients. The object of this study was to determine the
      effectiveness of a two-stage operation strategy for these lesions. Eight patients
      were operated on via anterior retropharyngeal approach and then stabilized with
      occipitocervical plates posteriorly in a second sitting. All neck pain and all
      dysphagia problems resolved. Partial neurologic improvement was achieved in three
      out of four patients. No postoperative infection was seen. The retropharyngeal
      approach to the upper cervical spine and anterior foramen magnum lesions is an
      effective alternative to transoral surgery because of low complication rates.
      Neoplastic lesions in the upper cervical spine can safely and effectively be
      operated with this technique. The general medical status of patients with
      malignancies does not permit too long, time-consuming operations. Stabilization
      of the spine in a separate operation increases patient tolerability without any
      morbidity.

PMID- 14704863
TI  - Genetics of diabetic cardiovascular disease: identification of a major
      susceptibility gene.
AB  - Differential susceptibility to coronary artery disease in the diabetic patient
      cannot be entirely explained by conventional cardiac risk factors or by diabetes
      characteristics such as the degree of glycaemic control or diabetes duration.
      There is a growing awareness that there exist susceptibility genes for the
      development of diabetic vascular complications. In this review, I focus on one
      such genetic susceptibility factor encoded at the haptoglobin locus.

PMID- 14704864
TI  - Features of macrovascular complications in type 2 diabetic patients.
AB  - Macroangiopathy is the most frequent complication in type 2 diabetic patients.
      Coexistence of atherosclerosis and diabetes may cause diagnostic difficulties
      resulting from an asymptomatic course. Alternatively, patients may overexpress
      their symptoms as the result of awareness the consequences of the disease.
      Careful assessment of clinical symptoms followed by preventive diagnosis of high
      risk patients as well as proper patient education allow for significant
      reductions of hazard of the consequences of macrovascular complications in
      diabetic patients

PMID- 14704865
TI  - Pharmacological treatment of diabetic patients with respect to prevention of
      macrovascular disease.
AB  - Prevention of atherosclerosis in type 2 diabetes ideally should start a long time
      before the diagnosis of diabetes since type 2 diabetes and atherosclerosis have a
      common background of metabolic syndrome. Identifying subjects with metabolic
      syndrome and beginning with lifestyle and drug interventions in such subjects
      would most probably delay the development of both diabetes and atherosclerosis.
      After the clinical diagnosis of diabetes, it is necessary to continue with
      multifactorial interventions targeted on risk factors, such as hyperglycaemia,
      dyslipidaemia and hypertension. Some interventions appear to have a benefit
      beyond the effect on risk factors. Effects of these interventions can be
      explained by their influence on some pathogenic mechanisms, such as insulin
      resistance and endothelial dysfunction. Multifactorial interventions decrease the
      incidence of macrovascular disease in diabetes at least by one-half and should be
      routinely used in the majority of patients with type 2 diabetes.

PMID- 14704866
TI  - Intensive treatment of coronary artery disease in diabetic patients in clinical
      practice: results of the MITRA study.
AB  - Patients with diabetes are at high risk for the development of coronary artery
      disease and have a significantly impaired prognosis after ST-elevation myocardial
      infarction (STEMI) as compared with non-diabetic patients. The beneficial effect
      of pharmaceutical treatment for secondary prevention after STEMI is proven also
      for diabetics, but little is known about its use in clinical practice. Between
      June 1994 and December 2000, consecutive patients with STEMI, admitted to
      hospital within 24 h of symptoms onset, were enrolled into the multicenter MITRA
      registry in 61 hospitals in Germany. We examined whether there were differences
      in the frequencies of pharmaceutical secondary prevention after STEMI and in long
      term outcomes between diabetics and nondiabetics in 8206 patients who had been
      discharged alive and followed for a mean period of 17 months. The prevalence of
      diabetes in 8206 patients discharged alive after acute STEMI was 18%. Diabetics
      were older and more often female, and more often already had prior myocardial
      infarction (MI) and stroke than non-diabetics. As chronic discharge medication,
      diabetics received aspirin and betablockers less often, but more often ACE
      inhibitors than non-diabetics. The mortality rate 17 months after STEMI was
      nearly twice as high in diabetics than in non-diabetics (19.1% vs. 10.4%, p<0.01
      at univariate analysis; OR=1.50 and 95% CI 1.27-1.77 at multivariate analysis).
      The combined endpoint of death, MI and stroke occurred in 25.8% of diabetics, but
      only in 15.8% of non-diabetics ( p<0.01). Long-term treatment with aspirin,
      betablockers and ACE inhibitors in diabetics was associated with a significant
      reduction of mortality. Diabetics received intensive pharmaceutical therapy for
      secondary prevention significantly less often than non-diabetics, although the
      beneficial effects of this treatment were similar or even more pronounced as
      compared with non-diabetics. Diabetes was an independent predictor of increased
      mortality in follow-up after acute STEMI. Intensifying secondary prevention by a
      more frequent use of established pharmaceutical regimes might improve the
      prognosis of diabetics after STEMI and prevent cardiovascular and cerebrovascular
      events.

PMID- 14704867
TI  - Interventions in diabetic patients after myocardial infarction.
AB  - Occurrence of a first acute myocardial infarction (AMI) is associated with
      further increase in risk of cardiovascular events. This risk is further increase
      is disproportionate in diabetics, who suffer from very high mortality short and
      long term after AMI. Factors responsible for the increased risk are only
      partially understood. Additional, properly designed, prospective epidemiological
      studies are needed for a better understanding of complicated diabetic
      macrovascular disease after the occurrence of the first event. These studies are
      also needed for designing interventional trials that target factors that carry
      the highest risk of new events. Published studies provide some insight into the
      issue of efficacy of blood pressure, cholesterol and blood glucose lowering
      strategies in the diabetic population. It remains unclear how important is the
      control of triglyceride concentration or other risk factors during various stages
      of recovery after AMI. The main reason is the lack of clinical trials. Evidence
      based approach to patients with diabetes and AMI indicates the importance of
      tight control of cholesterol, blood pressure and blood glucose concentration.
      Although other risk factors have not been extensively studied, it is reasonable
      to assume that other major risk factors, such as hypertriglyceridemia, should be
      targeted as well. In the meantime, more data need to be collected from
      prospective epidemiological and interventional protocols, if better control over
      the cardiovascular risk in this high-risk population is to be achieved.

PMID- 14704868
TI  - Retrospective analysis of cardiovascular outcomes in patients with type 2
      diabetes mellitus after the first acute myocardial infarction.
AB  - We retrospectively analyzed survival in patients with type 2 diabetes mellitus
      (DM) after first acute myocardial infarction (AMI). The study was conducted in 5
      sites in Poland and involved 521 patients who survived more than 30 days after
      AMI. In the 5-year period after the acute event, we investigated the following
      cardiovascular (CV) outcomes: death (overall mortality), next MI, stroke,
      hospitalization due to acute coronary symptoms (HACS), and composite outcomes
      (whichever occurred first). We also assessed: age, smoking habit, obesity,
      hypertension, dyslipidemia and coronary artery disease (CAD) diagnosed before
      AMI, and gender. 269 patients (52%) suffered one of the outcomes from the
      composite CV endpoint. HACS was the first event in 164 cases, MI in 59, death in
      32, and stroke in 14 patients. Analyzing the prevalence of individual CV events,
      we found: HACS in 184 patients (35%), next MI in 79 patients (15%), death in 59
      patients (11%), and stroke in 30 patients (6%). Only dyslipidemia, arterial
      hypertension, and CAD were independent risk factors with an impact on composite
      CV endpoint. Other analyzed risk factors like smoking and obesity did not have
      independent effects on the CV risk. In the retrospective analysis, we found that
      HACS was the most frequent CV event in individuals with type 2 DM after AMI. The
      CV risk in type 2 diabetics who suffered at least one myocardial infarction was
      further increased in those with coexisting dyslipidemia, arterial hypertension or
      CAD. These findings support the current guidelines which recommend aggressive
      management of CV risk factors including hypertension, dyslipidemia and CAD before
      a first myocardial infarction.

PMID- 14704869
TI  - Epidemiology of cardiovascular complications in type 2 diabetes mellitus.
AB  - Type 2 diabetes is increasing in epidemic proportions worldwide, and is strongly
      associated with atherosclerotic cardiovascular disease (CVD). Hyperglycaemia
      increases risk of CVD, but glycaemic control does not substantially reduce CVD
      risk. There are several potential explanations for this apparent paradox,
      including the roles of the metabolic syndrome and post-load hyperglycaemia in the
      association of type 2 diabetes and CVD.

PMID- 14704870
TI  - Hyperglycaemia and cardiovascular risk.
AB  - Cardiovascular diseases represent, today, the principal cause of mortality in the
      general population, especially in subjects with type 2 diabetes mellitus. In
      these patients the risk of death from cardiovascular diseases is equal to that of
      non-diabetic subjects with a previous episode of myocardial infarction. Many
      factors concur to determine such high risk. Hyperglycaemia contributes to the
      increase in morbidity and cardiovascular mortality associated with diabetes
      mellitus. Hyperglycaemia acts as a multiplier of cardiovascular risk due to
      frequent association of multiple risk factors in diabetic patients. Therefore,
      effective treatment requires a more complete assessment of quantitative and
      qualitative aspects of glycemic control as well as all components of the diabetic
      syndrome or, more commonly, metabolic syndrome.

PMID- 14704871
TI  - Clinical consequences of cardiovascular autonomic neuropathy in diabetic
      patients.
AB  - A wide range of clinical consequences of cardiovascular autonomic neuropathy
      (CAN) can be observed in diabetic patients and contributes to the clinical
      picture of the diabetic heart. Resting heart rate and cardiovascular reflexes as
      well as circadian heart rate variability may be altered by CAN in diabetes.
      Moreover, blood pressure is also influenced by sympathovagal imbalance. Postural
      hypotension is a clinical characteristic in diabetic subjects with CAN. Painless
      myocardial infarction, ischaemia and left ventricular dysfunction are also
      observed in some cases. Impairment of cardiac parasympathetic and sympathetic
      innervation as well as QT-interval prolongation may play a partial role in the
      pathogenic mechanism of sudden unexpected death in diabetic patients. The risk of
      surgical intervention and that of anaesthesia are increased due to abnormal
      cardiovascular reactions. Clinical symptoms and signs of CAN should be assessed
      as severe diabetic complication and the therapy is difficult in some cases. Taken
      together, symptoms and signs of CAN carry a poor prognosis in diabetic patients.

PMID- 14704872
TI  - Predisposing genetic factors for diabetic polyneuropathy in patients with type 1
      diabetes: a population-based case-control study.
AB  - Oxidative stress plays a key role in the development of microvascular
      complications of diabetes mellitus (DM). Antioxidant enzymes protect against the
      rapid onset of diabetic polyneuropathy (DPN) by reducing oxidative stress.
      Genetic variations that affect activity or expression levels of the antioxidant
      enzymes may therefore be associated with susceptibility to DPN. We examined
      polymorphic markers Ala(-9)Val in SOD2 gene and Arg213Gly in SOD3 gene for
      possible relation to DPN in Russian type 1 diabetic patients. Four hundred
      Russian white patients with type 1 diabetes were studied using neurological
      examination according to recommendations of the San Antonio Conference on
      Diabetic Neuropathy. Two groups were formed from the general sample. Definition
      of frequency distribution of the polymorphic markers was performed in these
      groups using the polymerase chain reaction. Genes encoding the enzymes Mn-SOD and
      extracellular superoxide dismutase (EC-SOD) were found to be associated with the
      pathogenesis of DPN.

PMID- 14704873
TI  - Hyperglycaemia and its relation to cardiovascular morbidity and mortality: has it
      been resolved?
AB  - Type 2 diabetes is preceded by long-standing asymptomatic hyperglycaemia. This
      prediabetic state is characterised by elevated post-prandial hyperglycaemia and
      yet normal fasting plasma glucose (FPG). The relationship between abnormal
      circulating glucose levels and the development of long-term diabetic
      complications became apparent 70 years ago, soon after the introduction of
      insulin and the prevention of early death due to ketoacidosis. The main issues
      regarding diabetes and the various target organs throughout the cardiovascular
      system, including coronary artery disease (CAD), peripheral vascular disease
      (PVD), increased intima-media thickness (IMT) and stroke, are as follows: CAD
      causes much of the serious morbidity and mortality in patients with diabetes, who
      have a 2- to 4-fold increased risk of CAD; epidemiological evidence confirms an
      association between diabetes and increased prevalence of PVD; and diabetes
      induces increased IMT and stroke by adversely affecting cerebrovascular
      circulation including the carotid artery, akin to its effects in the coronary and
      lower extremity vasculature. In diabetes, FPG and HbA(1C) are the main parameters
      of glucose metabolism used to monitor and control hyperglycaemia. Recently,
      particular emphasis has been placed on post-prandial plasma glucose as a
      parameter in the metabolic assessment of diabetic patients. Therefore, while
      addressing the question of hyperglycaemia and its relation to cardiovascular
      morbidity and mortality, we have to look for the possible mechanisms by which
      diabetic hyperglycaemia causes these complications. Then, we must examine the
      evidence on how the main parameters of glucose metabolism correlate with
      cardiovascular complications. This review addresses these issues.

PMID- 14704874
TI  - Diet and coronary heart disease in diabetes.
AB  - Persons with diabetes mellitus have an increased cardiovascular morbidity and
      mortality and therefore it is imperative to identify and treat aggressively all
      cardiovascular risk factors. The first line of intervention aiming to reduce the
      cardiovascular burden is dietary therapy along with other recommendations for
      lifestyle modification. Compliance with life-long dietary changes is a major
      issue and therefore emphasis should be placed on whole foods and dietary
      consumption habits. Also, dietary changes should be individualised according to
      patient's nutritional needs, lifestyle, cultural eating habits, taking into
      consideration all risk factors and existing comorbidities. Nevertheless, at least
      two main strategies have been proven to be effective in preventing coronary heart
      disease: 1). modification of fat quality through substitution of saturated fat,
      dietary cholesterol and trans- fatty acids with non-hydrogenated mono-and poly
      unsaturated fats and increased consumption of omega-3 fatty acids; 2).
      modification of carbohydrate quality by choosing high-cereal fiber and low
      glycaemic load intakes instead of refined grain products. Although the best diet
      for reducing cardiovascular risk remains uncertain, a combination of dietary
      interventions offers great benefits in preventing coronary events.

PMID- 14704875
TI  - Metabolic syndrome.
AB  - The metabolic syndrome is characterized by diabetes mellitus, obesity,
      hypertension, hyperlipidaemia and polycystic ovary syndrome. The lipid profiles
      of patient with metabolic syndrome is often characterized by the appearance of
      hypertrygliceridaemia and small, dense LDL-cholesterol, together with low HDL
      cholesterol. Patients with these abnormalities are at an increased risk for
      premature coronary artery disease. Treatment is a multifactorial process and
      includes modification of lifestyle factors such as diet and physical activity,
      weight reduction, correction of dyslipidemia, meticulous blood pressure and
      glycemic control. The case of a 36-year-old woman who develops metabolic syndrome
      is discussed.

PMID- 14704876
TI  - Patient with type 2 diabetes and stroke.
AB  - A case is presented of a type 2 diabetic patient who had a stroke. Various
      treatment issues are discussed.

PMID- 14704877
TI  - The patient with unstable angina: no evidence of MI.
AB  - A 53-year-old type 2 diabetic woman with macrovascular complications as well as
      the components of the metabolic syndrome presents with an unstable angina and ST
      depression on electromiogram. The negative impact of female gender, microvascular
      complications, and metabolic parameters on cardiovascular risk and prognosis, are
      emphasized. The lack of evidence for hormone replacement, antioxidant or
      universal folic acid therapy is underscored. Treatment options including PTCA and
      stenting augmented with low molecular weight heparin, clopidrogel and IIb/IIIa
      antagonists as well as optimal metabolic control are discussed.

PMID- 14704878
TI  - Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by
      HSV DNA detection in blood and successfully managed by liver transplantation.
AB  - We report a case of neonatal herpes presenting with liver failure and
      disseminated coagulopathy which followed unrecognised maternal primary genital
      herpes and was diagnosed by herpes simplex virus DNA detection in blood by
      polymerase chain reaction 2 weeks after initiation of empiric intravenous
      aciclovir. The child underwent liver transplantation while receiving suppressive
      antiviral therapy and remains well after 10 months of follow-up. CONCLUSION: our
      case highlights potential pitfalls in the diagnosis of neonatal herpes and
      indicates a role for blood herpes simplex virus polymerase chain reaction as a
      sensitive diagnostic tool in disseminated infection. It is one of very few
      reports where liver transplantation has been successfully carried out in a
      neonate with herpes simplex virus-induced liver failure.

PMID- 14704880
TI  - Forward masking of faces by spatially quantized random and structured masks: on
      the roles of wholistic configuration, local features, and spatial-frequency
      spectra in perceptual identification.
AB  - The forward masking of faces by spatially quantized masking images was studied.
      Masks were used in order to exert different types of degrading effects on the
      early representations in facial information processing. Three types of source
      images for masks were used: Same-face images (with regard to targets), different
      face images, and random Gaussian noise that was spectrally similar to facial
      images. They were all spatially quantized over the same range of quantization
      values. Same-face masks had virtually no masking effect at any of the
      quantization values. Different-face masks had strong masking effects only with
      fine-scale quantization, but led to the same efficiency of recognition as in the
      same-face mask condition with the coarsest quantization. Moreover, compared with
      the noise-mask condition, coarsely quantized different-face masks led to a
      relatively facilitated level of recognition efficiency. The masking effect of the
      noise mask did not vary significantly with the coarseness of quantization. The
      results supported neither a local feature processing account, nor a generalized
      spatial-frequency processing account, but were consistent with the microgenetic
      configuration-processing theory of face recognition. Also, the suitability of a
      spatial quantization technique for image configuration processing research has
      been demonstrated.

PMID- 14704881
TI  - Neuropsychological impairment following traumatic brain injury: a dose-response
      analysis.
AB  - Dikmen, Machamer, Winn, and Temkin (1995) administered the Halstead-Reitan
      Battery (HRB) to a sample of TBI patients. Similar patients were obtained from
      the second author (JEM) for two main purposes. First, we wished to determine if
      there is a dose-response relationship between TBI severity and residual cognitive
      deficit. Second, are Dikmen et al. results generalizable to other TBI samples?
      Analyses of the Meyers sample replicated the analyses of Dikmen sample. A
      significant dose-response relationship between loss of consciousness (LOC) and
      cognitive impairment was found using effect sizes for the Dikmen sample, as well
      as using regression-based normative T scores for the Meyers sample. The two
      methods were highly correlated with one another. Using mean scores for the six
      LOC-severity groups and the two samples resulted in a correlation coefficient
      r=.97, p<.0001. Results are presented for clinicians to use when assessing
      individual patients.

PMID- 14704882
TI  - An evaluation of the clinical utility of the OPIE-3 as an estimate of premorbid
      WAIS-III FSIQ.
AB  - The clinical utility of the Oklahoma Premorbid Intelligence Estimate--3 (OPIE-3;
      Schoenberg, Scott, Duff, & Adams, 2002) in estimating premorbid FSIQ was
      investigated with the WAIS-III standardization sample. The OPIE-3 algorithms
      combine Vocabulary, Information, Matrix Reasoning, and Picture Completion subtest
      raw scores with demographic variables to predict FSIQ. Estimated WAIS-III FSIQ
      scores are presented for patients' diagnosed with dementia, traumatic brain
      injury, Huntington's disease, Korsakoff's disease, chronic alcohol use, temporal
      lobectomy, and schizophrenia. A group of patients with depression was employed as
      a clinical control group. The OPIE-3V and OPIE-3MR algorithms performed well,
      with the average predicted FSIQ of the combined clinical sample approximating the
      mean FSIQ of healthy adults. The OPIE-3(Best), which is a procedure that employs
      either the OPIE-3V, OPIE-3MR, or OPIE-3(2ST) algorithms in a best performance
      method, is presented. Recommendations in the application of the OPIE-3 are made
      and future research is proposed.

PMID- 14704883
TI  - Qualitative analysis of verbal fluency before and after unilateral pallidotomy.
AB  - This study examined qualitative aspects of phonemic and semantic fluency before
      and after unilateral pallidotomy in patients with intractable Parkinson's Disease
      (PD). Specifically, clustering (number of similar words generated sequentially)
      and switching (number of changes or switches from one cluster to another) were
      evaluated for both fluency tasks. Twenty-five PD patients participated and were
      grouped according to whether they improved or declined on each of the fluency
      measures after surgery. Decliners evidenced decreased switching, but not
      clustering, suggesting difficulties with set-shifting and cognitive flexibility
      rather than a diminished semantic store of information or retrieval difficulties.
      Though consistent with hypotheses about difficulties with executive processing
      after pallidotomy, a series of correlational analyses with composite measures of
      neuropsychological functioning (attention, language, executive processing, and
      memory) suggest caution in interpreting these findings. In these analyses,
      clustering was not meaningfully related to any of the composites whereas
      switching was significantly and positively related to the composites; this
      pattern emerged, for the most part, on both fluency measures before and after
      surgery. Switching, but not clustering, was also significantly and positively
      correlated with total words generated on both semantic and phonemic fluency.
      Switching changes across time were also related to DRS changes post-pallidotomy.
      These correlational analyses challenge the specificity of the switching variable
      and, more broadly, the validity of these qualitative measures of verbal fluency.

PMID- 14704884
TI  - Number processing and calculation--normative data from healthy adults.
AB  - Despite the high incidence of numerical deficits in neurological patients, little
      attention has been paid to the development of diagnostic tools. In fact, most of
      the published reports on acquired numerical disorders, whether single case or
      group studies, do not refer to standardised measures of performance providing
      little, if any, control data specifically collected for the examination. In this
      study we present data of 282 healthy controls of different age groups and
      educational levels in a new battery of Number Processing and Calculation (NPC).
      The NPC battery includes a total of 35 tasks, assessing different counting
      abilities, various aspects of number comprehension (such as parity and magnitude
      judgements), numerical transcoding, calculation, arithmetic reasoning and
      conceptual knowledge. Special attention is paid to the assessment of different
      calculation abilities, including simple fact retrieval, rule based processing,
      mental calculation and written calculation in all four operations. Moreover, text
      problem solving is assessed as well as the understanding of arithmetic
      principles. Thus, the NPC battery differs from the EC 301 battery proposed by
      Deloche et al., 1994 (Dellatolas, Deloche, Basso, & Claros-Salinas, 2001) and
      allows a more fine grained diagnosis which is relevant for planning targeted
      interventions. The battery is easy to administer and does not require special
      materials or equipment.

PMID- 14704885
TI  - Age- and education-corrected independent normative data for the RBANS in a
      community dwelling elderly sample.
AB  - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS,
      Randolph, 1998) is likely to become a popular screening instrument for measuring
      cognitive functioning, particularly in elderly patients. As such, the present
      study attempted to extend the original normative data by reporting on RBANS
      performances in a group of 718 community dwelling older adults. Participants were
      recruited from an outpatient primary care setting, and were assessed for
      demographic, medical status, functional status, and quality of life information.
      Utilizing four empirically supported overlapping midpoint age ranges, individual
      subtest raw scores were converted to age-corrected scaled scores based on their
      position within a cumulative frequency distribution. These age-corrected scaled
      scores were also converted into education-corrected scaled scores using the same
      methodology across four education levels. Independent Index and Total scores were
      also calculated based on the data from this large elderly sample. These data may
      considerably advance the clinical utility of the RBANS by allowing clinicians to
      interpret individual subtests and make direct comparisons between subtests.
      Practitioners and researchers who elect to use the current normative data are
      encouraged to consider the similarities and differences between the present
      sample and their individual patients or research participants.

PMID- 14704886
TI  - Self-rated emotional functioning of patients with neurological or asymptomatic
      form of Wilson's disease.
AB  - Psychopathology was assessed in 50 patients with the neurological form of
      Wilson's disease (WD-N) and in 17 asymptomatic patients (WD-A) compared to
      matched healthy controls and to rheumatoid arthritis (RA) control patients using
      The Hopkins Symptom Checklist. As hypothesized, WD-N patients had significantly
      lower interpersonal sensitivity and aggression/hostility scores than had healthy
      controls, but did not differ from them either in depression or anxiety levels.
      Retarded depression and anxiety were higher among RA patients than in WD-N
      patients. This nondistressed response to the chronic disabling disease was even
      more salient in 19 WD patients with lesions in basal ganglia only. WD-A patients
      did not differ from their healthy peers, which suggests a tendency towards
      hypercompensation and denial in the former. WD-N patients' limited awareness of
      their deficits (including impaired control of affective behavior) seems to result
      from their brain damage implicating the basal ganglia.

PMID- 14704887
TI  - Late diagnosis of neurodegenerative disease in children: anosognosia by proxy.
AB  - Anosognosia is a term now generally defined as a failure to recognize the
      existence of disease processes, particularly those with a neurological basis.
      Denial of illness has been recognized in a large number of disorders, and is
      generally thought to have not only a central nervous system basis, but to also be
      influenced by the psychological processes of denial. This disorder has been
      reported in the adult population, and there are initial suggestions that it
      exists in children/adolescents. We propose to extend the concept of anosognosia
      to the caregivers of children who suffer significant dementia, and extended
      degeneration in neuropsychological and neurological functioning. We term this
      syndrome anosognosia by proxy. Three case examples are presented in which
      parents, teachers, and health care professionals observed extended deterioration
      in a child/adolescent's level of functioning prior to seeking appropriate
      diagnostic evaluations. Possible explanations for this process are advanced,
      including a combination of insidious onset coupled with the intimate nature of
      the child/parent relationship. The need for professional, teacher, and parent
      education on the nature of childhood degenerative neurological disorders is
      emphasized.

PMID- 14704888
TI  - Base rate of Hiscock Digit Memory Test failure in HIV-associated neurocognitive
      disorders.
AB  - There is an emergent need for base rate data on symptom validity tests (SVTs) in
      clinical populations that are likely to seek disability benefits. The inclusion
      of HIV under the Americans with Disabilities Act has prompted many persons with
      HIV-1 infection to apply for disability, which raises the concern that a subset
      of these individuals might feign cognitive deficits to obtain benefits. This
      brief report provides base rate data on one SVT, the Hiscock Digit Memory Test
      (HDMT), in a sample of 82 non-compensation-seeking, neuropsychologically impaired
      participants who met diagnostic criteria for an HIV-associated neurocognitive
      disorder. Approximately 98% of individuals with HIV-associated neurocognitive
      disorders performed above an established HDMT cutoff for suboptimal effort (i.e.,
      HDMT> or =90% accuracy), whilst 95% of the sample obtained perfect scores.
      Clinicians can therefore be confident that, in the absence of severe dementia or
      amnesia, HDMT scores below standard cutoffs are unlikely to be solely
      attributable to HIV-associated cognitive impairment.

PMID- 14704889
TI  - Victoria Symptom Validity Test scores of patients with profound memory
      impairment: nonlitigants case studies.
AB  - Victoria Symptom Validity Test (VSVT) scores from six nonlitigants with
      neurological illness accompanied by dense anterograde amnesia or severe memory
      impairment are presented. All of these patients obtained perfect or near perfect
      scores on the VSVT. These data add to the literature suggesting that the VSVT is
      insensitive to genuine neurologically-based memory impairment and provide an
      additional floor-level clinical benchmark against which to compare the
      performance of litigants.

PMID- 14704890
TI  - Exaggerated pain report in litigants with malingered neurocognitive dysfunction.
AB  - Twenty-nine litigants who met criteria for either definite or probable malingered
      neurocognitive dysfunction and reported chronic pain produced scores on the
      McGill Pain Questionnaire (MPQ), Pain Disability Index (PDI), and Modified
      Somatic Perception Questionnaire (MSPQ) that were significantly higher than
      scores produced by large samples of clinical pain patients. At 0.90 specificity,
      the MPQ, PDI, and MSPQ yielded sensitivities of 0.21, 0.59, and 0.90,
      respectively. The MSPQ alone, correlated significantly with the Lees-Haley Fake
      Bad Scale (FBS). Overall, the MSPQ is superior to the MPQ and PDI for detection
      of exaggerated pain symptoms.

PMID- 14704891
TI  - Personality characteristics of patients showing suboptimal cognitive effort.
AB  - This study examined the relationship between performance on the Portland Digit
      Recognition Test (PDRT) and the MMPI-2 in a group of veterans who were suspected
      of having motivation to exaggerate cognitive and/or psychiatric symptoms. Number
      correct on "easy" trials on the PDRT correlated inversely with MMPI-2 measures of
      psychopathology, whereas number correct on "hard" trials positively correlated
      with the same scales. Some individuals performed poorly across both types of PDRT
      trials and had significant MMPI-2 elevations, whereas others performed poorly
      only on "hard" PDRT trials and had less extreme MMPI-2 elevations. This study
      reinforces the need to assess the validity of both cognitive and psychiatric
      symptom complaints.

PMID- 14704892
TI  - Detection of malingering using atypical performance patterns on standard
      neuropsychological tests.
AB  - Cut-off scores defining clinically atypical patterns of performance were
      identified for five standard neuropsychological and psychological tests: Benton
      Visual Form Discrimination (VFD), Fingertapping (FT), WAIS-R Reliable Digit Span
      (RDS), Wisconsin Card Sorting Failure-to-Maintain Set (FMS), and the Lees-Haley
      Fake Bad Scale (FBS) from the MMPI-2. All possible pair-wise combinations of
      scores beyond cut-off (e.g., for VFD and FT; for RDS and FBS), correctly
      identified 21 of 24 subjects (87.5%) meeting criteria for definite malingered
      neurocognitive dysfunction, and 24 of 27 (88.9%) subjects with moderate to severe
      closed head injury. On cross-validation, 15 of 17 subjects (88.2%) meeting
      criteria for probable malingered neurocognitive dysfunction were correctly
      identified, with 13 of 13 nonlitigating neurologic patients, and 14 of 14
      nonlitigating psychiatric patients correctly classified as having motivationally
      preserved performance. Combining the derivation and cross-validation samples
      yielded a sensitivity of 87.8%, specificity of 94.4%, and combined hit rate of
      91.6%.

PMID- 14704893
TI  - Effectiveness of the Rey-Osterrieth Complex Figure Test and the Meyers and Meyers
      recognition trial in the detection of suspect effort.
AB  - The Rey-Osterrieth Complex Figure Test (ROCFT) is a popular measure of
      visuoconstructive skills and visual memory. A recognition memory trial was
      recently developed by Meyers and Meyers (1995) and attached to the standard
      administration of the ROCFT. The addition of this recognition paradigm (comprised
      of 12 small designs from the original ROCFT stimulus interspersed among 12 foils)
      makes ROCFT a potentially useful instrument in capturing suspect effort because
      patients attempting to feign memory difficulties typically operate from the
      misconception that recognition memory is as impaired as free recall in brain
      injury and, as a result, suppress recognition performance. The ROCFT (copy,
      immediate recall [i.e., 3-min recall], and the recognition trial) was
      administered to four sets of participants: 58 patients with suspect effort; 23
      neuropsychology clinic patients with verbal memory impairment, 17 clinic patients
      with visual memory impairment, and 30 clinic patients without memory impairment.
      Group comparisons revealed significant group differences in direct copy,
      immediate recall, and recognition scores of the ROCFT (p<.0001), with the suspect
      effort group displaying significantly lower performance on the copy and immediate
      recall scores than the verbal memory impaired and nonmemory impaired clinic
      patient groups, and significantly lower recognition scores than all three
      clinical groups. Furthermore, qualitative examination of the recognition trial
      revealed the presence of "atypical recognition errors" that were endorsed with
      significantly higher frequency by the suspect effort patients. A combination
      score incorporating the copy, true positive recognition, and atypical recognition
      error scores yielded a sensitivity of 74% while misclassifying only approximately
      4% of verbal memory impaired clinic patients, 12% of visual memory impaired
      clinic patients, and 3% of nonmemory impaired clinic patients. Thus, the
      ROCFT+recognition trial show considerable potential for detecting noncredible
      effort.

PMID- 14704894
TI  - WAIS-III processing speed index scores after TBI: the influence of working
      memory, psychomotor speed and perceptual processing.
AB  - This study investigates the extent to which working memory, motor speed and
      perceptual processing speed influence Wechsler Adult Intelligence Scale-III (WAIS
      III) Processing Speed Index (PSI) scores. Sixty-eight adult outpatients with
      Traumatic Brain Injury (TBI) of varying severity and complete data on all outcome
      measures were identified. Two cases with outlying values on one outcome measure
      were omitted from the final sample. Working memory was measured by the Working
      Memory Index score from the WAIS-III. Motor speed was measured as score on the
      Halstead-Reitan Finger Oscillation Test (finger tapping) and perceptual
      processing as score on the Trail Making Test--Part B. In hierarchical multiple
      regression analyses, working memory accounted for 10% of the variance in PSI
      scores, whereas motor speed only accounted for 3%. An independent measure of
      perceptual processing, Trail Making Test--B, accounted for 26% of the variance in
      WAIS-III PSI scores. The total variance accounted for by the three factors was
      56%. Findings confirm that the WAIS-III PSI scores of individuals who have
      received a TBI reflect perceptual processing speed, with an additional component
      attributable to working memory. Motor speed made only a small contribution to
      WAIS-III PSI scores in the present sample.

PMID- 14704895
TI  - A review of the influence of aqueous humor on immunity.
AB  - Regulation of immunity within the immune-privileged ocular microenvironment is a
      dynamic interaction of anatomical features, factors, and cells that work toward
      suppressing the induction inflammation. Immunosuppressive neuropeptides found in
      aqueous humor are central to this immunoregulation. These neuropeptides are alpha
      melanocyte-stimulating hormone, vasoactive intestinal peptide, calcitonin gene
      related peptide, and somatostatin. Along with transforming growth factor-beta2,
      the neuropeptides target specific cells and pathways in innate and adaptive
      immunity. These aqueous humor factors prevent pathogen-induced inflammation and
      activation of Th1 cells, while promoting induction of regulatory T cells.
      Therefore, the ocular microenvironment, through the constitutive production of
      immunosuppressive factors found in aqueous humor, maintains immune privilege by
      manipulating regional innate and adaptive immunity away from inflammatory
      responses.

PMID- 14704897
TI  - Interactions of olopatadine and selected antihistamines with model and natural
      membranes.
AB  - OBJECTIVE: Olopatadine, an effective topical ocular human conjunctival mast cell
      stabilizer/antihistaminic antiallergic drug, was evaluated and compared to
      selected classical antihistamines for their interaction with model and natural
      membranes to ascertain potential functional consequences of such interactions.
      METHODS: The model membranes examined consisted of the argon-buffer interface and
      monomolecular films of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) at
      the argon-buffer interface. Interactions with the model membranes were detected
      as changes in surface tension, i.e., surface pressure. Functional consequences of
      these interactions were assessed with natural membranes by 6-carboxyfluorescein
      leakage, hemoglobin release, lactate dehydrogenase release, and histamine release
      from appropriate cell types. RESULTS: Measurements at the argon-buffer interface
      revealed intrinsic surface activity for all agents that ranged from highly
      surface-active to weakly surface-active in the order of: desloratadine >
      clemastine > azelastine congruent with ketotifen > diphenhydramine> pyrilamine >
      emedastine > epinastine > or = olopatadine. This order of amphipathic behavior
      was confirmed for most of the compounds by estimates of their dissociation
      constants (K(d,L)) determined from interactions with SOPC monolayers adjusted to
      a surface pressure approximating that of natural membranes. Epinastine was the
      only antihistamine that showed a disproportionately greater increase in surface
      activity toward SOPC in monolayer when compared to other antihistamines.
      Dissociation constants could not be established for olopatadine because of its
      low affinity for both the argon-buffer interface and the SOPC monolayer.
      Functional consequences of these interactions were assessed with natural
      membranes by 6-carboxyfluorescein leakage (erythrocyte ghosts), hemoglobin
      release (erythrocytes), lactate dehydrogenase release (conjunctival mast cells,
      corneal epithelial cells), and histamine release (conjunctival mast cells). Aside
      from olopatadine and emedastine, all antihistamines promoted a concentration
      dependent leakage of hemoglobin from intact erythrocytes. The concentration of
      drug required to cause half-maximal hemoglobin release (H(50)) from erythrocytes
      correlated linearly (r = 0.98) with the SOPC dissociation constants (K( d,L))
      estimated for the different antihistaminic agents interacting with SOPC
      monolayers. A similarly high correlation (r = 0.85) emerged from a plot with a
      slope approaching unity that related drug concentrations required for half
      maximal hemoglobin leakage from erythrocytes to threshold doses of drug that
      caused histamine release from human conjunctival mast cells. Olopatadine was the
      only agent that did not promote membrane perturbation as monitored by either
      hemoglobin release from intact erythrocytes, LDH release from human conjunctival
      mast cells, or 6-carboxyfluorescein release from erythrocyte ghosts. Assessment
      of the lytic potential of marketed concentrations of ketotifen (0.025%),
      azelastine (0.05%), and epinastine (0.05%) revealed significant membrane
      perturbation of human conjunctival mast cells and, importantly, human corneal
      epithelial cells as indexed by LDH release. This was in contrast to marketed
      concentrations of olopatadine (0.1%) which maintained normal mast cell and
      corneal epithelial cell membrane function. CONCLUSIONS: Combined, these results
      support the notion that the disruption of natural cell membranes by surface
      active antihistamines occurs not through a receptor-mediated process, but is the
      consequence of a direct interaction of these agents with the cell membrane. This
      is corroborated by surface pressure-concentration isotherms for adsorption of
      five different antihistaminic agents to SOPC monolayers where 50% lysis occurred
      at a surface pressure of 42.9 +/- 1.1 mN/m. Olopatadine appears to be unique
      among the agents tested by demonstrating low intrinsic surface activity, thus
      limiting its interaction with natural membranes. At concentrations of about half
      maximal compound solubility (, 5.0 mM or a 0.19% drug solution), olopatadine
      generated SOPC monolayer surface pressures (i.e., 39.82 +/- 0.10 mN/m) that were
      below those that promoted membrane perturbation and onset of hemoglobin leakage.
      Olopatadine's restricted interaction with membrane phospholipids limits the
      degree of membrane perturbation and release of intracellular constituents,
      including histamine, LDH, and hemoglobin, which is believed to contribute to
      olopatadine's topical ocular comfort and patient acceptance.

PMID- 14704898
TI  - Clinical features of ocular toxocariasis in Japan.
AB  - PURPOSE: To characterize the clinical features of ocular toxocariasis and to
      describe the unique aspects of the disease in Japan. METHODS: Thirty-six cases
      diagnosed as ocular toxocariasis at the uveitis clinic of Tokyo Medical
      University Hospital were analyzed retrospectively. RESULTS: Thirty-six cases
      comprised 34 adults (average age: 39 +/- 10 years) and two nine-year-old boys.
      All cases were classified into two clinical types: posterior pole type (13 cases)
      and peripheral type (23 cases). Visual acuity was maintained over 20/20 in 50%
      and less than 20/200 in 14% of the cases. The peripheral type had worse outcomes
      than the posterior pole type in all of the endpoints examined: final visual
      outcome, frequency of ocular complications, and effectiveness of vitreous
      surgery. Antibody titers in intraocular fluids led to a diagnosis of ocular
      toxocariasis in eight seronegative cases of 33 cases examined for antibodies in
      both serum and intraocular fluid samples. CONCLUSIONS: The peripheral type had a
      worse prognosis than the posterior pole type. However, in general, ocular
      toxocariasis resulted in fair visual outcomes. The antibody titer in intraocular
      fluid was helpful in the diagnosis.

PMID- 14704899
TI  - Changing patterns of intraocular inflammatory disease in Japan.
AB  - PURPOSE: We investigated the frequencies and clinical characteristics of Japanese
      patients with uveitis. METHODS: Records of 189 patients referred from April 1999
      to March 2001 were retrospectively reviewed. RESULTS: Fifty-six patients (29.6%)
      had anterior uveitis, 13 (6.9%) intermediate uveitis, 59 (31.2%) posterior
      uveitis, 58 (30.7%) panuveitis, and three (1.6%) papillitis. The most common
      diagnoses were Vogt-Koyanagi-Harada (VKH) disease (10.1%), biopsy-proven or
      presumed sarcoidosis (9.5%), acute anterior uveitis (7.9%), tuberculosis (6.9%),
      and Behcet's disease (5.8%). Seventy-three patients (38.6%) were treated with
      local therapy alone, and 95 patients (50.3%) required systemic therapy. Ocular
      complications developed in 19.6% of patients, and systemic complications in 2.1%.
      CONCLUSIONS: These results confirm a continued high frequency of VKH disease and
      sarcoidosis, but suggest a decreased frequency of Behcet's disease and an
      increased frequency of tuberculosis. Roughly one-half of the patients required
      systemic treatment in addition to local therapy, and ocular and/or systemic
      complications developed in one-fifth of the patients.

PMID- 14704900
TI  - Uveitis referral pattern in a Midwest University Eye Center.
AB  - We determined the referral pattern and visual prognosis for patients with uveitis
      at a tertiary university eye center in the Midwestern U.S. over a five-year
      period. A retrospective chart review was conducted on 853 patients seen in the
      Department of Ophthalmology and Visual Sciences (DOVS) at Washington University
      and the Barnes Retina Institute (BRI) from 1990 to 1995. Recorded data on each
      patient included demographic information, anatomic diagnosis, etiologic
      diagnosis, pattern of uveitis, and best-corrected visual acuity (VA). Most
      patients originated from Missouri (65.3% [557/853]) and were Caucasian (88.4%
      [754/853]). There was an equal gender frequency (429 men, 424 women). The most
      frequent anatomic diagnosis was posterior uveitis (48.4% [414/853]), followed by
      anterior uveitis (22.3% [190/853]), panuveitis (18.4% [155/853]), and
      intermediate uveitis (10.9% [94/853]). An etiologic diagnosis was made in 69.3%
      (591/853) of the patients, with the most common diseases being cytomegalovirus
      (CMV) retinopathy, infectious endophthalmitis, pars planitis, multifocal
      choroiditis, and toxoplasmosis. The majority of uveitides presented with sudden
      onset (55.0% [469/853]) and lasted less than three months (51.9% [443/853]). A
      wide spectrum of uveitic disease is seen in a university eye center in the
      Midwest, including many cases with sudden-onset relatively short (<3 months)
      duration. The high frequency of posterior uveitis may be related to the
      appearance of newly recognized uveitic entities, such as multifocal choroiditis,
      birdshot retinochoroidopathy, and acute retinal necrosis.

PMID- 14704902
TI  - Atypical end-stage birdshot retinochoroidopathy.
AB  - PURPOSE: To describe a patient with birdshot retinochoroidopathy with peripheral
      pigmentary changes mimicking a pseudo-retinitis pigmentosa fundus. CASE REPORT: A
      60-year-old female patient was referred for bilateral uveitis. Fundus examination
      showed several creamy lesions in the choroid of both eyes. The patient was HLA
      A29-positive. A diagnosis of birdshot choroidopathy was made and she was treated
      with immunosupressive agents. Six years later, a pigmentation of the retina was
      noted in both eyes, which progressed to a bone-shaped appearance. DISCUSSION:
      Pigmentary reaction is a common feature of retinal lesions, although it rarely
      takes on a retinitis pigmentosa-like appearance. Furthermore, birdshot fundus
      lesions do not usually become highly hyperpigmented even after long-term
      evolution. This pigmentation may represent one type of the end-stage of birdshot
      retinochoroidopathy.

PMID- 14704901
TI  - Effect of a drug combination treatment on ocular perfusion in recurrent
      idiopathic intermediate uveitis.
AB  - PURPOSE: To test the effect of a drug combination therapy on ocular perfusion in
      human eyes affected by idiopathic intermediate uveitis. METHODS: Seven patients
      (12 eyes) showing active signs of intermediate uveitis, with at least two more
      similar episodes reported within the previous 12 months, were enrolled in a
      prospective case series. Two fellow healthy eyes of two of the enrolled patients
      were studied as internal controls. Color Doppler imaging of the central retinal
      artery (CRA), the ophthalmic artery (OA), and the posterior ciliary arteries
      (PCAs) was performed at the time of enrollment, and at 6 and 12 months after
      starting treatment with oral fluorocortolone, cyclosporine, and parenteral
      methotrexate. The best-corrected visual acuity was concurrently measured as a
      second parameter. RESULTS: In the 12 affected eyes, the mean visual acuity (+/
      SD) improved from 0.15(+/-0.12) to 0.04(+/-0.18) LogMAR (paired samples Student's
      t-test: p = 0.015). The resistivity index (RI +/- SD) of the CRA decreased from
      0.81(+/-0.13) to 0.71(+/-0.13)(p = 0.0091). Further, the variation of the RI in
      the PCAs reached a borderline significance (p = 0.062), decreasing from 0.71(+/
      0.12) to 0.61(+/-0.12). No significant changes were observed in the OA. Moreover,
      eyes showing a visual improvement of > or =0.1 (LogMAR) were more likely to show
      a > or =10% improvement of the RI for the CRA (Fisher's exact test: p = 0.018;
      power = 90%; alpha probability = 5%; odds ratio = 2,4). CONCLUSIONS: In eyes
      affected by idiopathic intermediate uveitis, treated with a systemic drug
      combination therapy, the improvement of the visual acuity seems to correlate with
      a proportional improvement of the retrobulbar circulation.

PMID- 14704903
TI  - Paracentral corneal melting in a patient with Vogt-Koyanagi-Harada's syndrome,
      psoriasis, and Hashimoto's thyroiditis.
AB  - The paper describes the occurrence of unilateral paracentral corneal melting in a
      65-year-old woman with ocular and systemic signs of Vogt-Koyanagi-Harada's
      syndrome (VKH), psoriasis, and Hashimoto's thyroiditis. Corneal melting, often
      occurring in association with systemic vasculitis and connective tissue diseases,
      has rarely been reported in relation to diffuse psoriasis and never in
      association with VKH. A possible relationship between corneal melting and VKH is
      suggested.

PMID- 14704904
TI  - Resolution of chicken pox neuroretinitis with oral acyclovir: a case report.
AB  - It is usual to consider chicken pox as a benign infectious disease with a few
      anterior segment ocular complications like conjunctivitis, keratitis,
      episcleritis, scleritis, iridocyclitis, and glaucoma. The retinal manifestations
      are necrotising retinitis, vitritis, neuroretinitis, and retinal detachments. We
      report a case of neuroretinitis following chicken pox in a 23-year-old male. The
      complication was resolved by treatment with oral acyclovir in combination with
      systemic steroids. This report highlights the necessity for fundus examination in
      cases of chickenpox exhibiting visual symptoms.

PMID- 14704907
TI  - In vitro release of mitomycin C from collagen implants.
AB  - PURPOSE: To study Mitomycin C Loaded Collagen Implant (CI) pharmacokinetics
      behaviour in vitro. METHODS: The CI were incubated for 15 minutes in different
      MMC loading solutions with the following concentrations: 0.03 mg/mL (n = 9), 0.3
      mg/mL (n = 10) and 3.0 mg/mL (n = 10). The loaded CI were transferred in 100
      micro L of 0.9% NaCl. Aqueous flow of 5 micro L/min was simulated. The MMC
      concentrations of the samples were determined by high performance liquid
      chromatography (HPLC). Dissolution kinetics were evaluated by a first-order
      process. The half-life of dissolution and the time of 95% dissolution were
      determined. RESULTS: The CI absorbed on average a MMC dose of 0.054, 0.530 and
      6.090 micro g when incubated in the different MMC loading solutions containing
      0.03 mg/mL, 0.3 mg/mL, 3.0 mg/mL of MMC, respectively. In the release
      experiments, the mean total dose delivered by CI was 0.0493, 0.585 and 5.291
      micro g. A linear correlation between loading concentration and the estimated
      total dose released was demonstrated. The kinetic parameters showed a fast MMC
      dissolution. The half-life of the 3 series was 8.8, 10.1 and 10.5 min.
      CONCLUSIONS: Commercially available CI can be loaded with MMC, and could provide
      relatively slower release than sponge delivery of MMC. Clinical implications of
      these results warrants further studies.

PMID- 14704908
TI  - Changes in HNK-1 epitope and collagen type IX in the aqueous humour of patients
      with pseudoexfoliation syndrome.
AB  - PURPOSE: To investigate alterations in the proteoglycan (PG) and
      glycosaminoglycan (GAG) content of the aqueous humour in patients with
      pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: Aqueous humor samples
      were obtained during cataract surgery from nineteen patients bearing PEX features
      and twenty-three age-matched normal controls. Protein and IgG were quantified
      densitometrically after their electrophoretic separation. Collagen type IX, 3
      sulphoglucuronic acid (HNK-1 epitope), biglycan and heparan sulphate
      proteoglycans were detected in Western and dot blots by using specific monoclonal
      antibodies (MAbs). The immunochemical analysis was performed in native aqueous
      humour or after degradation of the glycosaminoglycans with chondroitinases.
      RESULTS: Degradation of the samples with chondroitinases ABC, AC and B revealed
      that, in the aqueous humour from PEX eyes, collagen type IX and biglycan had a
      more dermatan sulphate than did normal eyes. In addition, more HNK-1 epitope was
      observed in PEX eyes, which after similar enzymatic treatment was found to be
      located mainly in dermatan sulphate sequences. 3-sulphoglucuronic acid was a
      constituent of the GAG chains of the collagen type IX. We found that the
      electrophoretic mobility of the bands of collagen type IX and HNK-1 epitope was
      exactly the same in the aqueous humour of normal and PEX samples; both migrated
      as four bands at 120, 113, 92.6 and 56 kDa. The PGs bearing heparan sulphate were
      found only in normal samples. Other PGs were not detected. CONCLUSIONS: Because
      no significant difference was observed in the concentration of albumin and IgG in
      PEX and normal samples, the blood-aqueous barrier was probably not significantly
      compromised in PEX patients with cataract but without open-angle glaucoma. The
      results support the hypothesis that the pathogenesis of PEX can be linked to
      disturbed metabolism of GAGs and PGs.

PMID- 14704909
TI  - Refractive evaluation in children with growth defect.
AB  - PURPOSE: Growth hormone (GH) is considered essential for postnatal somatic
      growth, exerting its effects on growth by hepatic production of IGF-I. IGF and
      other growth factors interact with the developing ocular tissues by influencing
      the synthesis of the extracellular matrix of the sclera and by inducing
      angiogenesis. The association between optic nerve hypoplasia, reduced retinal
      vascularization and GH deficiency (GHD) is well known. The purpose of this study
      is to evaluate the possible influence of congenital GHD on the refraction and on
      the emmetropization process. METHODS: Eighty children with congenital GHD had a
      thorough ophthalmologic examination, including cycloplegic refraction and axial
      length measurement. As a control group we enrolled 483 healthy children. RESULTS:
      In accordance with other epidemiological studies, the control group showed a
      slightly myopic mean defect; on the contrary, in GHD group we found a hyperopic
      defect, related to a shorter axial length, with statistically significant
      differences. CONCLUSIONS: Our findings emphasise the possible role of growth
      hormone in ocular development, and its interaction with the physiological process
      of emmetropization.

PMID- 14704910
TI  - Peroxynitrite-induced apoptosis in photoreceptor cells.
AB  - PURPOSE: To study the mechanisms of peroxynitrite-induced photoreceptor cell
      damage, using retinal cultures and a peroxynitrite donor, 3-morpholinosydnonimine
      (SIN-1). METHODS: Retinal explants obtained from 20-day-old Lewis rat pups, were
      exposed to SIN-1 for varying lengths of time at varying concentrations. Apoptosis
      in the photoreceptor cells was detected using the TdT-mediated dUTP-biotin nick
      end labeling (TUNEL) method and a DNA fragmentation assay. Selected retinal
      samples were processed for an ultrastructural analysis to confirm apoptosis. The
      retinas exposed to SIN-1 were tested for the expression of caspase-3 by
      immunohistochemistry and a Western blot analysis. The retinas were also evaluated
      for the prevention of apoptosis in the presence of the caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk). RESULTS: The
      retinal explants exposed to SIN-1 showed a significant increase in the presence
      of TUNEL-positive photoreceptor cells. Similarly lineal increases in TUNEL
      positive cells were seen in the presence of increasing concentrations of SIN-1.
      DNA ladder formation was seen with the exposure of SIN-1. Ultrastructurally, SIN
      1 exposed retinas revealed typical apoptotic changes in the photoreceptor cell
      nuclei. The retinas preincubated with urate for 6 hours and exposed to SIN-1 for
      16 hours showed significantly fewer TUNEL-positive cells compared to the retinas
      exposed to SIN-1 alone (p < 0.05). Moreover, the retinas exposed to SIN-1 showed
      the expression of caspase-3. This expression, as well as the number of apoptotic
      photoreceptors, significantly decreased in the presence of Z-VAD-fmk.
      CONCLUSIONS: These results show that peroxynitrite induces apoptosis in
      photoreceptor cells and that such retinal damage appears to be mediated by
      caspase-3. The apoptotic process can be minimized by peroxynitrite scavenger
      urate, as well as by the caspase inhibitor Z-VAD-fmk.

PMID- 14704911
TI  - Quantitative and conformational characterization of lysozyme deposited on
      balafilcon and etafilcon contact lens materials.
AB  - PURPOSE: To determine whether differences in lysozyme deposition and/or activity
      exist on worn etafilcon and balafilcon contact lenses following care with a
      polyquaternium-based system (PQ) or a polyhexanide-based system (PHMB). METHODS:
      Following acid-based deposit extraction, lysozyme concentration was determined
      via Western blotting and lysozyme activity was determined by a micrococcyl assay.
      RESULTS: Lysozyme deposition on etafilcon lenses was greater following
      disinfection with the PHMB-based system (1551 +/- 371 micro g/lens vs 935 +/- 271
      micro g/lens; p < 0.001). Deposition on balafilcon lenses was not influenced by
      the care regimen (10 +/- 3.5 micro g/lens vs 10 +/- 5 micro g/lens; p = 0.89).
      For both materials, the percentage of denatured lysozyme was greater when they
      were exposed to the PHMB-based system (28 vs 21%; p = 0.05 (etafilcon) and 57 vs
      40%; p = 0.04 (balafilcon)). CONCLUSIONS: The quantity and conformation of
      lysozyme deposited on hydrogel contact lens materials is significantly influenced
      by both lens material and care regimen.

PMID- 14704912
TI  - Expression and distribution of tissue transglutaminase in normal and injured rat
      cornea.
AB  - PURPOSE: To determine the expression and distribution of tissue transglutaminase
      (TG(C)) and extracellular matrix (ECM) proteins in rat cornea during epithelial
      wound healing. METHODS: Corneal epithelial defects were created in rat corneas,
      and TG(C) expression was examined by Northern blot analysis, in situ
      hybridization, and immunohistochemical staining after the injury. The presence of
      fibrinogen, laminin-1, nidogen/entactin, and type collagen was also determined
      immunohistochemically. RESULTS: TG(C) was expressed in normal corneas. During the
      early wound healing process, TG(C) mRNA expression was up-regulated and TG(C)
      immunoreactivity was predominantly expressed in the migrating epithelial cells.
      ECM proteins were also expressed in a similar pattern as TG(C). CONCLUSIONS: The
      sites and time course of TG(C) expression indicate that TG(C) probably plays a
      role in maintaining the homeostasis of the cornea and in promoting epithelial
      wound healing. The simultaneous expression of TG(C) and ECM proteins suggests
      that the ECM proteins probably operate in concert with TG(C) in corneal wound
      healing.

PMID- 14704913
TI  - Diabetes has an additive effect on neural apoptosis in rat retina with
      chronically elevated intraocular pressure.
AB  - PURPOSE: Diabetes mellitus (DM) is a risk factor for open-angle glaucoma,
      although the mechanistic interrelationship of the two is debatable. The purpose
      of this study is to test whether DM augments neural apoptosis in rat retina with
      chronically elevated intraocular pressure (IOP). METHODS: Sprague-Dawley rats
      were made diabetic by intraperitoneal injection of streptozotocin (STZ). At one
      month after STZ injection, three episcleral veins in one eye were cauterized to
      elevate IOP. Rats without STZ injection were treated likewise as diabetic
      controls. At 2 weeks, 1 month, and 2 months after cauterization, the retina was
      dissected, flat-mounted, and subjected to terminal dUTP nick end labeling (TUNEL)
      staining. TUNEL positive cells per unit area of the whole retina were measured.
      RESULTS: DM did not affect base line IOP or augment IOP elevation due to
      episcleral vein cauterization. TUNEL positive cells, which primarily consisted of
      the neurons and glial cells in the inner retina including retinal ganglion cell
      (RGC), were counted consistently eight times more in the diabetic retina without
      IOP elevation than diabetic controls (n = 9, p < 0.001). The cauterization
      significantly elevated IOP up to 28.9 mmHg (p < 0.001), which was reduced over
      time, and substantially induced apoptosis in a IOP-dependent fashion (p < 0.001).
      Ocular hypertensive retinas with DM had significantly more TUNEL positive cells
      than those without DM despite of the similar time course of IOP changes (p <
      0.001). CONCLUSIONS: DM has an additive effect on apoptosis induction by chronic
      elevation of IOP. Diabetes may act as a risk factor of open-angle glaucoma by
      increasing susceptibility of retinal cells including retinal ganglion cells to
      apoptosis triggered by additional stresses such as elevated IOP.

PMID- 14704915
TI  - The effects of forward light scattering on the multifocal electroretinogram.
AB  - PURPOSE: To study the effects of forward light scattering on the multifocal
      electroretinogram (mfERG). METHODS: Thirty young normal subjects were recruited
      for this study. The mfERG was measured under five conditions. (1) no light
      scattering (stimulus contrast 93%), (2) mild light scattering (stimulus contrast
      80%), (3) moderate light scattering (stimulus contrast 50%), (4) no light
      scattering (stimulus contrast 80%), and (5) no light scattering (stimulus
      contrast 50%). RESULTS: The amplitudes of N1 and P1 from the central retina did
      not change significantly, but the amplitudes of N1 and P1 in the mid peripheral
      retina increased with the increase of forward light scattering. By comparing
      conditions 1, 4 and 5, it was shown that the amplitudes of N1 and P1 decreased at
      all eccentricities when stimulus contrast reduced from 93% to 50%. CONCLUSIONS:
      This study suggests that the topography and waveform of the mfERG could be
      affected by forward light scattering.

PMID- 14704914
TI  - Clinical evaluation of an HP-guar gellable lubricant eye drop for the relief of
      dryness of the eye.
AB  - PURPOSE: To evaluate the efficacy of a new lubricant eye drop containing
      polyethylene glycol 400 and propylene glycol demulcents with hydroxypropyl-guar
      as a gelling agent (Test Product) to a system with carboxymethylcellulose
      (Control Product) for reducing dry eye signs and symptoms. METHODS: Eighty-seven
      dry eye volunteers were enrolled at seven sites for this six-week, concurrently
      controlled, double-masked clinical study. RESULTS: The Test Product significantly
      reduced conjunctival staining (p = 0.025) and temporal corneal staining (p =
      0.024) compared to the Control. The Test Product also significantly reduced
      symptoms of dryness in the morning and evening, compared to the Control (p =
      0.015 and p = 0.023, respectively). Subjects in the Test treatment group reported
      lower frequencies of foreign body sensation and felt their eyes were "refreshed
      longer" compared to those in the Control group (p = 0.033 and p = 0.037,
      respectively). CONCLUSIONS: The Test Product was more effective at reducing both
      the signs and symptoms of dry eye compared to the carboxymethylcellulose
      containing Control.

PMID- 14704917
TI  - An update on retinal circulation assessment technologies.

PMID- 14704918
TI  - Effect of P-glycoprotein on the ocular disposition of a model substrate,
      quinidine.
AB  - PURPOSE: The objective of this study was to determine the effect of the multi
      drug efflux transport protein, P-glycoprotein (P-gp), on the ocular distribution
      of a model substrate, quinidine. METHODS: Male New Zealand albino rabbits (2-2.5
      kg) were employed in these studies. Animals were kept under anesthesia and a
      concentric microdialysis probe was implanted in the vitreous humor and a linear
      probe in the anterior chamber. Isotonic phosphate buffered saline was perfused
      through the probes, and samples were collected every 20 minutes over a period of
      10 hours. Quinidine was administered both systemically (5 mg/kg bodyweight) and
      intravitreally (5.68 microg and 0.568 microg). Inhibition experiments were
      performed in vivo in the presence of verapamil, which is a known P-gp inhibitor.
      RESULTS: Vitreal pharmacokinetic parameters of quinidine in the presence of
      verapamil, i.e., Area under the curve (AUC) (39.27 +/- 6.47 min. microg/ml),
      maximum concentration achieved (Cmax) (0.095 +/- 0.011 microg/ml), vitreal
      elimination half-life (231.96 +/- 10.77 min), vitreal permeation half-life (16.57
      +/- 6.96 min) were significantly different from the control values (19.21 +/-
      3.73 min. microg/ml, 0.05 +/- 0.008 microg/ml, 165.08 +/- 31.5 min, 43.29 +/-
      12.5 min respectively). A significant elevation in anterior chamber Cmax and AUC
      was also observed in the presence of verapamil. Verapamil had no significant
      effect on vitreal kinetics of quinidine following intravitreal dose of 5.68 micro
      g, but a significant difference was observed at a lower dose of quinidine (0.568
      microg). A decrease in vitreal elimination half-life and AUC was observed in the
      presence of verapamil relative to control. Ocular kinetics of fluorescein was
      studied to ascertain ocular barrier integrity in the presence of verapamil.
      Western-blot analysis of retina-choroid sections indicates expression of P-gp on
      rabbit retina-choroid. CONCLUSION: Results suggest the involvement of a multi
      drug efflux transporter on the retinal pigment epithelium and neural retina
      affecting the intraocular kinetics of its substrates following systemic and
      intravitreal administrations.

PMID- 14704919
TI  - Episcleral venous pressure of mouse eye and effect of body position.
AB  - PURPOSE: To measure the episcleral venous pressure (EVP) of the mouse eye and to
      investigate the effect of body position on EVP and intraocular pressure (IOP).
      METHODS: A microneedle connected to a pressure transducer was used to measure IOP
      in NIH Swiss white mice. To measure EVP, a reservoir connected to this transducer
      allowed modulation of the intracameral pressure by changing its height. As
      intracameral pressure was gradually lowered, there was an observable reflux of
      erythrocytes from an episcleral vein into Schlemm's canal. The IOP at which this
      occurred was the endpoint of the EVP measurement. EVP and IOP were measured in a
      horizontal body position (0 degrees ) analogous to an awake mouse and at 30
      degrees and 60 degrees head-down body position from the horizontal position. EVP
      was measured twice in each eye of 6 mice. RESULTS: Mean IOP at 0 degrees, 30
      degrees and 60 degrees of head-down position was 16.5 +/- 0.6, 18.2 +/- 0.6, and
      19.5 +/- 1.8 mmHg, respectively. EVP (horizontal) was 9.6 +/- 1.3 mmHg (N = 6
      eyes). EVP significantly increased with increasing degree of head-down position
      (SNK test, p < 0.05). EVP at 30 degrees and 60 degrees of head-down position was
      11.2 +/- 1.3 and 13.3 +/- 1.5 mmHg, respectively. CONCLUSIONS: Mouse EVP was
      successfully measured based on the detection of erythrocyte reflux from an
      episcleral vein into Schlemm's canal. Both EVP and IOP increased with the degree
      of the head-down body position.

PMID- 14704920
TI  - Refractive error, cognitive demand and nearwork-induced transient myopia.
AB  - PURPOSE: Whereas many previous studies have identified the association between
      sustained near work and myopia, few have assessed the influence of concomitant
      levels of cognitive effort. This study investigates the effect of cognitive
      effort on near-work induced transient myopia (NITM). METHODS: Subjects comprised
      of six early onset myopes (EOM; mean age 23.7 yrs; mean onset 10.8 yrs), six late
      onset myopes (LOM; mean age 23.2 yrs; mean onset 20.0 yrs) and six emmetropes
      (EMM; mean age 23.8 yrs). Dynamic, monocular, ocular accommodation was measured
      with the Shin-Nippon SRW-5000 autorefractor. Subjects engaged passively or
      actively in a 5 minute arithmetic sum checking task presented monocularly on an
      LCD monitor via a Badal optical system. In all conditions the task was initially
      located at near (4.50 D) and immediately following the task instantaneously
      changed to far (0.00 D) for a further 5 minutes. The combinations of active (A)
      and passive (P) cognition were randomly allocated as P:P; A:P; A:A; P:A. RESULTS:
      For the initial near task, LOMs were shown to have a significantly less accurate
      accommodative response than either EOMs or EMMs (p < 0.001). For the far task,
      post hoc analyses for refraction identified EOMs as demonstrating significant
      NITM compared to LOMs (p < 0.05), who in turn showed greater NITM than EMMs (p <
      0.001). The data show that for EOMs the level of cognitive activity operating
      during the near and far tasks determines the persistence of NITM; persistence
      being maximal when active cognition at near is followed by passive cognition at
      far. CONCLUSIONS: Compared with EMMs, EOMs and LOMs are particularly susceptible
      to NITM such that sustained near vision reduces subsequent accommodative accuracy
      for far vision. It is speculated that the marked NITM found in EOM may be a
      consequence of the crystalline lens thinning shown to be a developmental feature
      of EOM. Whereas the role of small amounts of retinal defocus in myopigenesis
      remains equivocal, the results show that account needs to be taken of cognitive
      demand in assessing phenomena such as NITM.

PMID- 14704921
TI  - Neural pathways subserving negative lens-induced emmetropization in chicks-
      insights from selective lesions of the optic nerve and ciliary nerve.
AB  - PURPOSE: Active emmetropization describes the process by which young eyes
      regulate their growth to eliminate refractive errors. The purpose of this study
      was to re-investigate the role of the brain in compensation to imposed hyperopic
      defocus (negative lenses), specifically, to assess whether a retina-brain link
      and/or an intact ciliary nerve are required for this emmetropizing response. Data
      from previous related studies are equivocal. METHODS: Unilateral lesion surgery
      involving either or both optic nerve section (ONS) and ciliary nerve section
      (CNS), was performed on 2-3 day old White-Leghorn chicks to interrupt
      communication between the eye (retina in the case of ONS) and brain. After a
      recovery period of 4 days, lesioned eyes were fitted with either -5 or -15 D
      lenses or diffusers (6-9 per group). An additional lesion group underwent
      unilateral CNS and was fitted with -5 D lenses bilaterally. Finally 3 groups that
      underwent the same unilateral optical treatments but no surgery were included as
      controls for analyzing lesion-induced changes. Complete sets of measurements,
      involving retinoscopy for refractive errors, and high frequency A-scan
      ultrasonography for axial ocular dimensions, were made at the beginning
      (baseline), and end of a 4 day treatment period. Additional ultrasonography data
      were collected after 1 and 2 days of treatment. Optical treatment effects were
      expressed as changes in interocular differences from baseline values. RESULTS:
      All three lesions produced hyperopic shifts in refraction (evident in baseline
      values), although this effect was minimal for the ONS+CNS group. Choroidal
      thickening as well as increased anterior chamber depth and lens thinning were
      observed in all cases but vitreous chamber depth was reduced in only the ONS
      group. In response to the -5 D lens, the control (nonlesioned) group showed
      nearly complete compensation, while full compensation was not achieved to the -15
      D lens over this short treatment period. The diffuser group showed the largest
      change, which was also in the direction of myopia. Both the ONS and CNS groups
      showed near normal compensation, as indexed by the changes in refractive errors
      relative to their respective baseline values. In contrast, the ONS+CNS lens
      groups overcompensated, by 130% and 54% for the -5 D and the -15 D lens groups
      respectively. Form deprivation responses were slightly exaggerated in both ONS
      and ONS+CNS groups, the latter group again showing the largest response. Enhanced
      vitreous chamber growth was evident under all conditions and correlated well with
      the refractive changes across the groups. DISCUSSION: The data imply that an
      intact retina-brain link is not required for compensation to hyperopic defocus
      and thus emmetropization. However, the data also imply interactions between
      higher centers and the eye. The emmetropization set-point appears to be
      recalibrated after ONS surgery. The data also indicate a role of the ciliary
      nerve as an important conduit for signals that exercise a restraining influence
      on eye growth.

PMID- 14704922
TI  - Ocular toxicity of intravitreal trovafloxacin in the pigmented rabbit.
AB  - PURPOSE: Trovafloxacin is an expanded spectrum, newer-generation fluoroquinolone
      antibiotic with improved Gram-positive and anaerobic activity compared with
      existing quinolones, while maintaining Gram-negative activity comparable to
      ciprofloxacin. Given its broad spectrum of activity, trovafloxacin may have
      potential use for treatment of acute bacterial endophthalmitis. This study
      examined the toxicity of intravitreally administered trovafloxacin in the
      pigmented rabbit eye. METHODS: Doses of trovafloxacin ranging from 12.5 microg to
      1000 microg were injected into the mid-vitreous of Dutch Belted rabbit eyes.
      Clinical examination was performed at 1, 3, and 14 days following injection.
      Animals were sacrificed and eyes were enucleated 14 days following injection.
      Light microscopy (LM) and transmission electron microscopy (TEM) studies of the
      optic nerve head, medullary ray, and inferior retina were performed to determine
      toxicity. RESULTS: At intravitreal doses of 500 microg and less, no toxicity was
      observed at the ophthalmoscopic or light microscopic level. By TEM, a dose
      dependent increase in injury to retinal pigment epithelium, photoreceptors, and
      nerve fibers in the optic nerve head and medullary ray was observed from 50
      microg to 500 microg. No toxicity was noted at doses of 12.5 microg and 25
      microg. At doses of 750 microg and above, edema of the medullary ray was noted on
      ophthalmoscopy. Swelling of the peripapillary medullary ray and necrosis of the
      inferior retina were evident on LM. CONCLUSION: Intravitreal trovafloxacin doses
      of 50 microg and higher in the pigmented rabbit eye cause retinal and nerve fiber
      injury. Intravitreal doses 25 microg and lower appear to be safe, with no
      evidence of ocular toxicity.

PMID- 14704923
TI  - Ultrastructure of the vitreoretinal interface following the removal of the
      internal limiting membrane using indocyanine green.
AB  - PURPOSE: To investigate the morphological changes of the vitreoretinal interface
      following the removal of the internal limiting membrane (ILM) using indocyanine
      green (ICG). METHODS: In 10 primate eyes, a pars plana vitrectomy was performed
      followed by ICG-assisted peeling of the ILM. Morphological changes in the exposed
      inner surface of the retina were investigated by electronmicroscopy immediately,
      3, 6 and 12 months after the ILM removal. RESULTS: The excised ILM was associated
      with fragments of glial tissue. The Muller cell processes were damaged and
      removed at the corresponding region of the retina. Regenerative spindle-shaped
      Muller cell processes were observed focally showing a meshwork like configuration
      at 3 and 6 months. Flattened and stretched processes were observed at 12 months;
      however, there was no apparent ILM regeneration. CONCLUSIONS: ICG assisted ILM
      peeling was observed to cause mild damage to the vitreoretinal interface, which
      did not completely recover within 12 months.

PMID- 14704926
TI  - [39th National Psychiatry Congress].

PMID- 14704927
TI  - [Comparison of regional cerebral blood flow in deficit and nondeficit
      schizophrenic patients].
AB  - OBJECTIVE: Brain imaging techniques are commonly used to define changes in the
      structure and functions of the brain in schizophrenic patients. The relationships
      between brain images and the cluster of symptoms provide us with more information
      about heterogeneous forms of schizophrenia. The aim of this study is to compare
      the regional blood flow of deficit and nondeficit syndrome schizophrenic
      patients. METHOD: Forty schizophrenic patients under the age of 65, without
      physical or neurological illness, mental retardation, a history of substance
      abuse, or ECT over the previous six months were included in the study. The Scale
      for the Assessment of Positive Symptoms, Scale for the Assessment of Negative
      Symptoms, UKU Side Effect Rating Scale, Hamilton Rating Scale for Depression and
      The Schedule for the Deficit Syndrome (SDS) were used to evaluate the patients.
      The regional cerebral blood flow was measured semiquantitatively by SPECT imaging
      using radiopharmaceutical Tc 99m-HMPAO. RESULTS: There was a significant
      reduction in the regional blood flow of deficit syndrome patients compared to
      nondeficit ones in the left frontal cortex (p= 0.002), right frontal cortex (p=
      0.006) and right temporal cortex (p= 0.04). CONCLUSION: We suggest that
      dysfunctions in some neuroanatomic structures are related to deficit syndrome and
      the concept of deficit syndrome is important for understanding underlying
      pathophysiologic mechanisms.

PMID- 14704928
TI  - [Reliability and validity of the Cornell Scale for Depression in Dementia in an
      elderly Turkish population].
AB  - OBJECTIVE: The reliability and validity of the Cornell Scale for Depression in
      Dementia were investigated in a Turkish population over 60 years of age. METHOD:
      Forty-six male and 34 female demented elderly people classified as demented
      according to DSM-IV criteria were included in the study. The Structured Clinical
      Interview for DSM-IV Clinical Version (SCID-I) was completed for all subjects to
      establish the diagnosis of major depression. The Cornell Scale for Depression in
      Dementia (CSDD), Geriatric Depression Scale (GDS), Mini Mental State Examination
      (MMSE) and Global Deterioration Scale (GDS) were used. RESULTS: A high test
      retest correlation level (r: 0.93) was obtained for the total scores of the
      scale. The scale also showed high internal consistency (a: 0.86). The validity
      analysis of the scale resulted in a significant difference (p<0.001) between the
      total scores of the group with dementia and depression and the group with
      dementia but without depression. Two items (9-19) showed a low correlation
      (r<.30) in the test-retest analysis. On the other hand, two items (6-19) had a
      low item-total score correlation (r<.30). CONCLUSIONS: The results indicated that
      the scale is reliable and valid for diagnosing depression in dementia in an
      elderly Turkish population. We expect that the Cornell Scale for Depression in
      Dementia will be a useful instrument in pharmacological investigations and in
      studies of the phenomenology and course of depressive symptoms in demented
      patients.

PMID- 14704929
TI  - [The Well-Being Questionnaire-12: an evaluation of its validity and reliability
      in Turkish people with end-stage renal disease].
AB  - OBJECTIVE: The aim of the present investigation was to test the psychometric
      properties of the Turkish version of the Well-Being Questionnaire-12 (WBQ-12) in
      patients with end-stage renal disease. METHOD: The subjects included in the study
      were patients with end-stage renal disease treated in Hemodialysis Unit of
      Baskent University Medical Hospital. The Patient Information Sheet, the Mini
      Mental Test, the WBQ-12, the Hospital Anxiety and Depression Scale (HAD) were
      applied to a total of 60 patients ranging from 19-71 years old. The WBQ-12 was
      applied for test-retest reliability assessment in 3-7 days after first interview.
      RESULTS: The item-total score correlation of the WBQ-12's items was 0.43,
      Cronbach's alpha coefficient was 0.87, and test-retest correlation coefficient
      was 0.80. The optimum cut-off score for the WBQ-12 with respect to detecting
      anxiety and/or depressive disorder was determined to be 10. Using this cut-off
      point, the sensitivity, specificity, positive predictive value, and negative
      predictive value of the WBQ-12 were 0.87, 0.73, 0.50 and 0.92, respectively.
      CONCLUSION: This short instrument is easy to administer and may be considered a
      useful tool for both clinicians and researchers to assess the psychological well
      being of patients with end-stage renal disease which has high psychiatric
      comorbidity, and causes disability in high level.

PMID- 14704930
TI  - [An Experience of a Clubhouse run by Families and Volunteers for Schizophrenia
      Rehabilitation].
AB  - OBJECTIVE: To test the efficacy of a non-governmental psychosocial rehabilitation
      program (Psychosocial Rehabilitation Clubhouse), which was developed by the
      authors and thought to be easy to put into practice for patients with
      schizophrenia. METHOD: Patients with schizophrenia (n: 14) were serviced at
      "Izmit Our Garden Solidarity Foundation of Families of Patients with
      Schizophrenia" for 8 months. Rehabilitation services were conducted wholly by
      families and volunteers, and run by a volunteer psychologist. Program included
      daily activities, cultural, leisure and social activities, one day in a week.
      Patients were assessed by using the Quality of Life Scale (QLS), Social
      Functioning Scale (SFS), Global Assessment Scale (GAS), and Positive and Negative
      Syndrome Scale (PANNS) at baseline and at the end of the study. RESULTS: All
      patients (n:14) completed the program with 73% mean presence in the activities.
      Increase of the social functioning and the good clinical outcome was observed in
      patients. The results of the scales were as follows: SFS at baseline 105.1+/
      20.6, in the end 133.7+/-17.1, (p<0.001); GAS at baseline 53.4+/-10.5, in the end
      66.0+/-8.1, (p<0.001); QLS at baseline 62.8+/-17.4, in the end 93.4+/-19.8,
      (p<0.001); and PANSS in the baseline 70.3+/-16.9, in the end 61.9+/-16.5,
      (p<0.002). CONCLUSION: Psychosocial clubhouse rehabilitation program run by
      patients' families and volunteers in a small foundation environment, which is the
      first trial in Turkey, has been carried out successfully.

PMID- 14704931
TI  - [Clinical drug research from medical ethics and legal perspectives].
AB  - Medical ethics and law in clinical drug research are the two main points that
      have been discussed in public and medical circles. Conducting drug research on
      "easily affected and vulnerable groups", such as psychiatric patients, has always
      been a controversial issue in medicine. How should human subjects be protected,
      especially psychiatric patients, who are defined as "vulnerable subjects and
      groups"; what are the ethically and legally justifiable reasons for basing drug
      research on psychiatric patients; and what can be said about responsibilities in
      the context of medical ethics and law? Patients who are in the mentioned groups
      can not be informed clearly about the characteristics of research which they
      would be involved in. In recent years psychiatric, geriatric, anesthesiology and
      pediatric patients are defined as "patients who do not have the ability for
      consent". In this article answers will be given to questions such as why medical
      ethics is interested in clinical drug research, and what kind of roles should
      ethics play in drug research. The situation worldwide will be analyzed from a
      historical approach with regard to laws and regulations concerning drug research.
      The legal rights of human subjects who have the ability to give informed consent
      and of those who do not will be discussed and the place of psychiatric patients
      as human subjects in drug research will be addressed. Some unethical examples and
      their consequences will be considered and discussed. In this context, a critical
      evaluation will be made of the situation in Turkey.

PMID- 14704932
TI  - [Neurobiological consequences of early life stressors].
AB  - This article reviews the neurobiological effects of psychosocial stress. In the
      first part, the results of childhood traumas, neurobiological models which
      explain the effects of psychosocial stress and animal studies on this subject are
      introduced. In a number of studies, an increase in the adulthood prevalence of
      depression, anxiety disorders and other psychiatric disorders was shown in
      children who were exposed to early life stress. Pre-clinical and clinical studies
      have shown that early life stressors cause endocrine, autonomous and behavioral
      stress responses as a result of permanent sensitivity in corticotropin releasing
      factor and other neurotransmitter systems in the central nervous system. As a
      result of this sensitivity, repeating stressors may play an important role in the
      pathogenesis of depression, anxiety disorders and psychophysiologic disorders. In
      contrast with the numerous studies investigating the long term effects of early
      life stressors on the brain, there are very few studies investigating the acute
      effects of these stressors. In spite of these limitations, it is known that
      psychosocial stressors may cause different neurobiological results in adults and
      children. After reviewing the relationship between psychosocial stressors and the
      neurobiology of affective disorders, it is explained how psychosocial stresses
      cause sensitivities in the central nervous system and how these sensitivities
      cause illness. These interactions have implications for treatment in the light of
      the explained mechanisms. In the last part of the article, new treatment
      strategies developed for correcting the effects of stress on the central nervous
      system are introduced.

PMID- 14704933
TI  - [Difficulties of an approach to an incest case: a case report].
AB  - OBJECTIVE: Incest is one of the most difficult issues to be talked over and
      studied. Experience of sexual harassment is not only hard for the victim, but
      also for the rest of the family. Sexual harassment experienced in a family
      especially in father-daughter relationship is an enormously difficult and
      traumatic event. In this situation, the fundamental needs of trust and protection
      of the child is violated by the parent who is supposed to be responsible for
      establishing them and this is true for all the family. It is essential for the
      therapy of the victim to receive immediate professional help, to be able to
      disclose his/her experiences, and to receive support from his/her environment. It
      is apparent that intensive intervention immediately after trauma is vital in
      decreasing the possible effects of the trauma. This report presents a 16 years
      old female, applied to Crisis Intervention Center of Ankara University, who was
      sexually abused by her father. The patient and other family members, except
      father, were treated by an intense crisis intervention technique and all family
      members benefited from the treatment. Unfortunately, the father who didn't join
      the treatment process, committed suicide. This paper presents how effective and
      functional it can be to utilize crisis intervention, with a multidisciplinary
      group using multiple approaches, when sufficient social support is available.
      Negative consequences of neglecting the abuser due to counter-transference are
      also discussed.

PMID- 14704934
TI  - [100th Congress of the German Society of Ophthalmology 26-9 September 2002].

PMID- 14704935
TI  - [100th Congress of the German Society of Ophthalmology 26-9 September 2002].

PMID- 14704936
TI  - [What's new in ophthalmic anaesthesia?].
AB  - In the past few years, there have been many changes in ophthalmic anaesthesia.
      Application of drugs in general anaesthesia with excellent controllability
      enhances patient safety and allows a more efficient OR-management. Regional
      anaesthesia is gaining widespread use for ophthalmic surgery, especially topical
      anaesthesia for cataract surgery. Patients for ophthalmic surgery concomitantly
      often display high age and a high level of co-morbidity and, therefore, belong to
      the anaesthesiological risk groups ASA III-IV. Life-threatening adverse events
      including cardiovascular depression are associated with general and regional
      anaesthesia. Intervention by anaesthesiologists is frequently required for
      treatment of hypertension or dysrhythmias, and sedation. Thus, monitored
      anaesthesia care ("standby") is justified. Drugs applied for regional and general
      anaesthesia may change intraocular pressure. There are a lot of publications
      about the impact of anaesthesia on intraocular pressure (IOD), however, few on
      the effects of anaesthesia on pulsatile ocular blood flow. it has to be kept in
      mind that the effects of anaesthesia on intra-ocular pressure and pulsatile
      ocular blood flow may diverge. To avoid an increase of the IOD, especially during
      anaesthesia induction, drugs, such as succinylcholin, rocuronium and opiates, in
      particular remifentanil, can be applied. In addition, the use of the laryngeal
      mask may be advantageous compared to general anaesthesia associated with
      laryngoscopic tracheal intubation. The management of patients treated with
      anticoagulants and antiplatelet agents, has to be taken on the balance of risks.
      There are risks not only in continuing therapy, but also in discontinuing it
      perioperatively. Postoperative nausea and vomiting (PONV) remains a distressing
      and common problem after strabismus repair in particular in children. The
      incidence of PONV depends on the type of ophthalmic surgery and drugs applied. To
      reduce PONV in ophthalmic surgery, application of long-lasting opiates should be
      avoided, and non-opiate analgesics and, depending on the kind of operation,
      antiemetic prophylactics are recommended.

PMID- 14704937
TI  - [Optical coherence tomography versus ultrasound biomicroscopy of conjunctival and
      eyelid lesions].
AB  - BACKGROUND: The value of ultrasound biomicroscopy in the diagnosis of
      conjunctival and eyelid lesions is still unknown. METHOD: For the examination of
      conjunctival and eyelid lesions, we used an anterior segment OCT (4optics,
      Lubeck) and an ultrasound biomicroscope (Humphrey, Zeiss, Oberkochen) with high
      frequency transducer (30 MHz). Included in this study were all patients with
      conjunctival and eyelid lesions, which were consecutively operated on between
      December 2002 and January 2003. Histological examination of the excised tissue
      was performed. RESULTS: 38 tumours of 35 patients, aged 8 - 93 years, were
      examined. 13 tumours were conjunctival lesions and 25 tumours were eyelid
      lesions. Histological examination displayed the presence of a pterygium (8/38), a
      seborrhoic keratosis (7/38), a cyst of the eyelid (5/38), a basal cell carcinoma
      of the eyelid (4/38), a compound naevus of the conjunctiva (4/38), a chalazion
      (3/38), a primary acquired melanosis (1/38), an actinic keratosis (1/38), a
      naevus (1/38), a cavernous haemangioma (1/38), a melanoma in situ (1/38), a
      foreign body (1/38), and an epidermoid cyst (1/38). Using both ultrasound
      biomicroscopy and optical coherence tomography (OCT) we were able to demonstrate
      a cystic tumour in the five patients (13 %) with a cyst of the eyelid. With OCT
      and with ultrasoundbiomicroscopy in all patients with pterygium a slit was found
      and in patients with compound naevus very small cystic structures were seen, but
      with OCT the imaging was more reliable. In patients with solid tumours the
      definite diagnosis could not be differentiated by ultrasound biomicroscopy or OCT
      alone. Using OCT, assessment of the margins of the tumours (particularly in
      depth) was impossible or uncertain. CONCLUSION: Compared to ultrasound
      biomicroscopy OCT is able to show very small cystic structures more distinctly.
      For assessing the margins of the tumour ultrasound biomicroscopy is the better
      tool.

PMID- 14704938
TI  - Comparative study of human keratocyte density after corneal grafting by using
      confocal microscopy in vivo.
AB  - PURPOSE: In a case control study we determined keratocyte density and size of
      nuclear area in the central segment of the corneal stroma. METHODS: We compared
      20 corneas after keratoplasty with 24 eyes of normal healthy individuals. Both
      groups were matched according to age. Keratocyte density and nuclear area were
      analyzed using Nidek Confoscan 2 separately for each group. In corneal graft
      recipients we studied how the mentioned variables were influenced by age of
      corneal graft donor (ranged from 4- to 71-years old) and by the time from surgery
      (8 to 77 months). RESULTS: The comparison of healthy controls and patients with
      keratoplasty revealed no changes in keratocyte density and the size of nuclear
      area in central stromal layers. In patients after keratoplasty donor age
      influenced an increase in keratocyte nuclei area only in the posterior stroma
      layer (p = 0.042). No such changes were observed in anterior and midstroma
      layers. Donor age was not found to be significant for keratocyte density in any
      of the layers. Time from surgery neither influenced changes in keratocyte density
      nor in keratocyte nuclei area. CONCLUSIONS: In our study using confocal
      microscopy in vivo we found that corneal grafting does not influence keratocyte
      density and nuclear area in individual layers of the central corneal stroma
      segment (anterior, midstroma and posterior layers). Donor age influenced an
      increase in keratocyte nuclei area only in the posterior stroma layer.

PMID- 14704939
TI  - Intraocular pressure after phacoemulsification with posterior chamber lens
      implantation in open-angle glaucoma.
AB  - BACKGROUND: To evaluate changes in intraocular pressure (IOP) after
      phacoemulsification (Phaco) with posterior chamber lens (PC IOL) implantation in
      eyes with primary open-angle glaucoma (POAG) at least 2 years after surgery.
      PATIENTS AND METHODS: 19 eyes of 13 POAG patients who underwent uneventful clear
      cornea Phaco with PC IOL implantation and with follow-up of at least 2 years
      after surgery were included in this retrospective study. None of them had
      previous intraocular surgery or argon laser trabeculoplasty. RESULTS: The average
      preoperative IOP was 16.9 +/- 2.02 mm Hg. The average follow-up of was 36 +/-
      11.8 months. 1 week after surgery a significant decrease in average IOP was
      observed (13.8 +/- 3.0 mm Hg; P = 0.000). 1 and 4 months after surgery IOP was
      still significantly lower than preoperatively. 8 months after surgery IOP
      significantly increased to 15.9 mm Hg (+/- 2.9 mm Hg; P = 0.022) with respect to
      1 week postoperatively, but then again significantly decreased to 15.5 mm Hg (+/-
      2.6 mm Hg; P = 0.020) 1 year after surgery and stayed approximately the same at 2
      and 3 years after surgery. After 4 years the average IOP was 15.0 mm Hg (+/- 3.1
      mm Hg; P = 0.216), that was statistically insignificant because of the small
      number of patients. In 79% (15 eyes) of our cases medical antiglaucoma treatment
      was unchanged, in 21% (4 eyes) the therapy was reduced. CONCLUSIONS: Uneventful
      Phaco with PC IOL implantation in good medically controlled POAG eyes was
      associated with a statistically significant long-term decrease in IOP, allowing
      the reduction of postoperative antiglaucoma medications in more than 20% of the
      eyes.

PMID- 14704940
TI  - Effect of soft contact lenses on the measurements of intraocular pressure with
      non-contact pneumotonometry.
AB  - PURPOSE: To evaluate the effect of soft contact lenses with different lens power
      on the measured value of the intraocular pressure with non-contact
      pneumotonometry. METHODS: 120 eyes (80 healthy volunteers: 50 women, 30 men, aged
      22 to 61 years) were included in this study. Intraocular pressure was measured
      with a pneumotonometer Canon X-10 before and after insertion of the Ciba Vision
      Focus Night&Day soft contact lens. We used contact lenses with different lens
      power of + 0.25 D, + 1.00 D, + 4.00 D, - 1.00 D, and - 4.00 D. The averages of
      three measurements were taken as representative IOP values that were
      statistically evaluated. RESULTS: IOP measured over myopic lenses of - 1.00 and -
      4.00 D showed lower values within the mean range of 1 mm Hg. The difference
      between the measurements over the myopic lenses was mostly smaller than +/- 2 mm
      Hg (78% when using - 1.00 D and 90% when using - 4.00 D contact lens). All the
      differences using + 0.25 D contact lens were smaller than +/- 2 mm Hg. The
      difference was considerably higher in measurements over + 1.00 and + 4.00
      hyperopic contact lenses and showed strong increase with the lens power.
      CONCLUSIONS: In our study we showed that intraocular pressure can be reliably
      measured with non-contact pneumotonometry over myopic lenses or hypermetropic
      lenses with small lens power. This suggests that non-contact pneumotonometry is a
      useful method in patients wearing therapeutic contact lenses and contact lens
      wearers who, when measuring the eye pressure, would not need to remove the
      contact lenses before the examination.

PMID- 14704941
TI  - Influence of corneal thickness on comparative intraocular pressure measurements
      with Goldmann and non-contact tonometers in keratoconus.
AB  - BACKGROUND: The influence of corneal thickness and curvature on the difference
      between intraocular pressure (IOP) measurements obtained with non-contact (NCT)
      and those with the Goldmann applanation tonometer (GAT) was studied in patients
      with keratoconus. MATERIALS AND METHODS: We examined 113 patients with
      keratoconus. IOP was measured by the Canon TX 10 non-contact tonometer and the
      Goldmann tonometer, corneal curvature and thickness were obtained by Humphrey
      Automatic Refractometer Keratometer and Orbscan Version 3.0 Bausch & Lomb
      Surgical. RESULTS: The IOP measured by NCT was significantly lower than that
      measured by GAT. The mean pachymetry of the thinnest point was 423.15 +/- 98.43
      microm for the right eyes and 426.7 +/- 93.88 microm for the left eyes. The
      difference between NCT-GAT and corneal thickness showed a significant negative
      correlation (r = - 0.427, p < 0.0001; t = - 3.677, p < 0.0001). Values of NCT
      measurements were significantly increasing with corneal thickness (F = 6.505, p <
      0.0001 for right eyes and F = 4.37, p = 0.004 for left eyes), whilst GAT
      measurements did not show a significant influence of the corneal thickness. The
      keratometry had no effect on the difference between NCT-GAT measurements (t =
      1.090, p = 0.278). CONCLUSIONS: The thin cornea has more influence on the
      measurement with NCT than GAT. The relative precision of NCT compared with GAT
      seems to be influenced by the corneal thickness.

PMID- 14704942
TI  - [Efficacy of selective laser trabeculoplasty in the treatment of primary open
      angle glaucoma].
AB  - BACKGROUND: Our aim was to investigate the efficacy of selective laser
      trabeculoplasty (SLT) for the treatment of primary open-angle glaucoma (POAG) in
      a prospective clinical study. PATIENTS AND METHODS: In 36 eyes of 36 patients
      suffering from uncontrolled POAG, treatment was carried out with a frequency
      doubled, Q-switched Nd:YAG laser (532 nm). The intraocular pressure (IOP) was
      measured before the treatment and one day, one week, one month and 3, 6, 12, 18,
      24, 30, 36, 42 and 48 months after. A failure was defined as an IOP reduction of
      less than 20% from pretreatment IOP, or a progression of visual field or optic
      disc damage requiring filtering surgery. The hypotensive medication during the
      study period remained unchanged. RESULTS: The mean follow-up time was 34 months
      (SD 12.9). The mean pretreatment IOP was 22.9 mm Hg (SD 2.1). At one month of
      follow-up, the mean IOP reduction was 5.3 mm Hg (SD 2.1) or 23.1% and at 6 months
      5.6 mm Hg (SD 2.6) or 24.5%. At 12 months of follow-up, the mean IOP reduction
      was 5.6 mm Hg (SD 2.3) or 24.5% and at 24 months 6.2 mm Hg (SD 2.5) or 27%. At 36
      months of follow-up, the mean IOP reduction was 6.4 mm Hg (SD 2.1) or 27.4% and
      at the end of 48 months of follow-up, the mean IOP reduction was 5.9 mm Hg (SD
      2.0) or 25.4%. The success rate after 12 months determined from the Kaplan-Meier
      survival analysis was 97%, after 24 months 88%, after 36 months 76% and after 48
      months 71%. CONCLUSION: SLT is an effective procedure for the treatment of POAG.

PMID- 14704943
TI  - Echographic follow-up of malignant melanoma of the choroid after brachytherapy
      with 106Ru.
AB  - BACKGROUND: The objective of this study was to analyse the dynamics and
      importance of different choroidal melanoma echographic parameters (height, base
      diameter, volume and internal reflectivity) after (106)Ru brachytherapy (BT Ru)
      and to assess at what time after treatment it is most appropriate to evaluate the
      outcome. PATIENTS AND METHODS: A retrospective study was performed in 65
      patients. The mean height of tumours was 4.8 mm. The mean dose to the tumour apex
      was 100 Gy. The patients were followed-up for a period of 22 to 169 months.
      RESULTS: With regard to the treatment outcome, the patients were categorised into
      three groups: successfully treated patients, in whom the tumour regressed with no
      metastatic spread, unsuccessfully treated patients, in whom enucleation was
      required because of the recurrence or further growth, and deceased patients. The
      largest decrease of tumour size was observed within 12 months after
      brachytherapy. The groups of deceased and successfully treated patients did not
      significantly differ as to the extent and rate of tumour decrease. In the local
      failure group, the tumour decrease in the first year after brachytherapy was less
      than in the other two groups. CONCLUSIONS: To follow-up the regression of the
      malignant melanoma of the choroid after brachytherapy with (106)Ru, the most
      reliable measurements were those of the tumour height. In the tumours that
      regressed, it is appropriate to evaluate the efficiency of treatment one year
      after brachytherapy. Recurrent growth may be expected in the tumours that
      regressed poorly.

PMID- 14704944
TI  - Fundus autofluorescence imaging in Best's vitelliform dystrophy.
AB  - BACKGROUND: It is well known that with age lipofuscin accumulates in the retinal
      pigment epithelium (RPE). In many inherited macular dystrophies such as Best's
      disease abnormally high levels of lipofuscin were found by histopathological
      studies. In recent years, it has become possible to detect and image fundus
      autofluorescence in the living eye as an index of lipofuscin accumulation in the
      RPE. The aim of our study was to document the intrinsic fundus autofluorescence
      in patients with different stages of Best's disease and to correlate fundoscopic
      features with visual function in these patients. METHODS: Images of fundus
      autofluorescence were obtained from 10 patients with Best's vitelliform
      dystrophy, using a Heidelberg Retina Angiograph (HRA). Argon laser light (488 nm)
      was used for illumination, and a wide-bandpass filter with a cutoff of 500 nm was
      inserted in front of the detector to obtain the autofluorescence images. Images
      were compared with fundus appearance and fluorescein angiograms as well as with
      visual acuity, colour vision, visual fields and electrophysiological recordings
      in these patients. RESULTS: In initial stages of Best's disease, there were
      localised areas of hyperfluorescence centrally in the fovea, later being replaced
      by central hypofluorescence (atrophic) areas surrounded by hyperfluorescent
      rings. The evolution of autofluorescence pattern showed centrifugal spreading of
      retinal dysfunction from the centre towards periphery. Atrophic regions of the
      RPE were associated with low levels of background autofluorescence, lower visual
      acuity, abnormal colour vision (70% of patients), central scotomas (85% of
      patients) and poorer electrophysiological results (reduced PERG responses in 45%
      of patients with Best's disease). CONCLUSIONS: Fundus autofluorescence imaging
      provides new information regarding the content and spatial distribution of RPE
      lipofuscin in eyes with Best's disease, which appears to correspond to retinal
      function. This may "in vivo" give important clues to the pathogenesis and
      progression of Best's disease in which non-invasive autofluorescence imaging may
      replace fluorescein angiography.

PMID- 14704945
TI  - [Reduction of retinal light sensitivity in diabetic patients].
AB  - BACKGROUND: Visual field loss in diabetic patients has received comparatively
      little attention. The aim of the present study was firstly to assess the
      influence of type 2 diabetes mellitus on retinal light sensitivity in diabetic
      patients without signs of diabetic retinopathy (DR) and secondly to assess the
      association between visual field loss and the severity of nonproliferative DR.
      PATIENTS AND METHODS: 151 eyes of 151 diabetic patients with type 2 diabetes
      mellitus and 30 eyes of 30 healthy volunteers were included in our study. Visual
      acuity was 0.7 or better with correction. DR staging was based on a modified
      Airlie-House classification. The eyes were divided into four groups: no DR, mild
      NPDR, moderate NPDR and severe NPDR. Ophthalmic examination was normal in all
      diabetic patients, except for DR. All participants underwent visual field testing
      with the C 30-2 program of the Humphrey field analyser. RESULTS: Retinal light
      sensitivity was significantly reduced before clinically detectable DR with MD
      (mean deviation) p values less than 10% in 14.3% (8 of 56 eyes). Patients with
      mild NPDR had a significant reduction of retinal sensitivity in 21.1% (8 of 38
      eyes), with moderate NPDR in 45.8% (11 of 24 eyes) and with severe NPDR in 63.6%
      (21 of 33 eyes). PSD (pattern standard deviation) p values less than 10% were
      observed in 7.1% (4 of 56 eyes) in patients without DR, with mild DR in 31.6% (12
      of 38 eyes), with moderate in 50% (12 of 24 eyes) and in patients with severe DR
      in 60.1% (20 of 33 eyes). Using the analytical STATPAC program of the Humphrey
      Field Analyzer, the reduction of retinal sensitivity was significant between
      controls and diabetic patients without DR and between individual groups of
      diabetic patients. CONCLUSIONS: The severity of visual field loss was greater in
      advanced stages of DR. In diabetic patients with severe DR, a significant
      reduction of retinal light sensitivity was observed in more than 60%. In diabetic
      patients without DR, despite no evident capillary closure on fluorescein
      angiography--similar as in the control group, where retinal sensitivity was
      normal in all cases--a significant reduction of retinal sensitivity was found in
      more than 14.3%.

PMID- 14704946
TI  - The - 429 T/C and - 374 T/A gene polymorphisms of the receptor of advanced
      glycation end products gene are not risk factors for diabetic retinopathy in
      Caucasians with type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to look for a relationship between the - 429
      T/C and the - 374 T/A gene polymorphisms of the receptor of advanced glycation
      end products (RAGE) gene and the development of diabetic retinopathy in
      Caucasians with type 2 diabetes. MATERIALS AND METHODS: One hundred and sixteen
      subjects with type 2 diabetes and diabetic retinopathy were compared to 70
      diabetic subjects without diabetic retinopathy. Additionally, 76 subjects with
      proliferative diabetic retinopathy (a subgroup of diabetic retinopathy) were
      compared to 70 diabetic subjects without diabetic retinopathy. RESULTS: The - 429
      T/C and the - 374 T/A RAGE gene distributions in patients with diabetic
      retinopathy (- 429 T/C: CC 0.9%, TC 25.9%, TT 73.2%; - 374 T/A: AA 9.5%, TA
      47.4%, TT 43.1%) were not significantly different from those of diabetic subjects
      without retinopathy (- 429 T/C: CC 0%, TC 25.7%, TT 74.3%; - 374 T/A: AA 15.7%,
      TA 42.9%, TT 41.4%). Moreover, the - 429 T/C and the - 374 T/A RAGE gene
      distributions in patients with proliferative diabetic retinopathy were not
      statistically significantly different from those in diabetic subjects without
      retinopathy. CONCLUSION: Our study failed to demonstrate an association between
      either - 429 T/C or - 374 T/A gene polymorphism of the RAGE gene and diabetic
      retinopathy in Caucasians with type 2 diabetes. Additionally, we failed to
      demonstrate an association between either - 429 T/C or - 374 T/A gene
      polymorphism of the RAGE gene and proliferative diabetic retinopathy in
      Caucasians with type 2 diabetes.

PMID- 14704947
TI  - [Laudatio for Prof. Dr. med. Dr. h. c. mult. Gottfried Otto Helmut Naumann on the
      occasion of the academic ceremony of his retirement].

PMID- 14704948
TI  - Motors, adaptors, and receptors: key elements of neuronal transport.

PMID- 14704949
TI  - Myosin-dependent transport in neurons.
AB  - Axonal transport in neurons has been shown to be microtubule dependent, driven by
      the molecular motor proteins kinesin and dynein. However, organelles undergoing
      fast transport can often pause or rapidly change directions without apparent
      dissociation from their transport tracks. Cytoskeletal polymers such as
      neurofilaments and microtubules have also been shown to make infrequent but rapid
      movements in axons indicating that their transport is likely to involve molecular
      motors. In addition, neurons have multiple compartments that are devoid of
      microtubules where transport of organelles is still seen to occur. These areas
      are rich in other cytoskeletal polymers such as actin filaments. Transported
      organelles have been shown to associate with multiple motor proteins including
      myosins. This suggests that nonmicrotubule-based transport may be myosin driven.
      In this review we will focus our attention on myosin motors known to be present
      in neurons and evaluate the evidence that they contribute to transport or other
      functions in the different compartments of the neuron.

PMID- 14704950
TI  - Short-range axonal/dendritic transport by myosin-V: A model for vesicle delivery
      to the synapse.
AB  - Myosin-V is a versatile motor involved in short-range axonal/dendritic transport
      of vesicles in the actin-rich cortex and synaptic regions of nerve cells. It
      binds to several different kinds of neuronal vesicles by its globular tail domain
      but the mechanism by which it is recruited to these vesicles is not known. In
      this study, we used an in vitro motility assay derived from axoplasm of the squid
      giant axon to study the effects of the globular tail domain on the transport of
      neuronal vesicles. We found that the globular tail fragment of myosin-V inhibited
      actin-based vesicle transport by displacing native myosin-V and binding to
      vesicles. The globular tail domain pulled down kinesin, a known binding partner
      of myosin-V, in affinity isolation experiments. These data confirmed earlier
      evidence that kinesin and myosin-V interact to form a hetero-motor complex. The
      formation of a kinesin/myosin-V hetero-motor complex on vesicles is thought to
      facilitate the coordination of long-range movement on microtubules and short
      range movement on actin filaments. The direct interaction of motors from both
      filament systems may represent the mechanism by which the transition of vesicles
      from microtubules to actin filaments is regulated. These results are the first
      demonstration that the recombinant tail of myosin-V inhibits vesicle transport in
      an in vitro motility assay. Future experiments are designed to determine the
      functional significance of the interaction between myosin-V and kinesin and to
      identify other proteins that bind to the globular tail domain of myosin-V.

PMID- 14704951
TI  - Dynein: An ancient motor protein involved in multiple modes of transport.
AB  - Cytoplasmic dynein has long been thought to be responsible for retrograde axonal
      transport. As the number of cellular roles for this multifunctional protein has
      expanded, the complexity of its contribution to axonal transport has increased.
      In this article the increasing evidence for a role for cytoplasmic dynein in
      anterograde as well as retrograde transport is discussed. The current status of
      the complex dynein cargo-binding mechanism is evaluated. Finally, recent genetic
      evidence supporting a role in axonal transport and revealing a role in
      neurodegenerative conditions is reviewed.

PMID- 14704952
TI  - Axonal transport versus dendritic transport.
AB  - Neurons have polarized processes for information output and input, axons, and
      dendrites. This polarized architecture is essential for the neuronal function. An
      increasing number of molecular components that mediate neuronal polarity
      establishment have been characterized over the past few years. The vast majority
      of these molecules include proteins that act in scaffolding protein complexes to
      sustain the polarized anchoring of molecules. In addition, more signaling and
      cytoskeleton-associated proteins have been proposed for establishment of
      polarity. It has become evident that dendritic and axonal transport of molecules
      depends on scaffolding/adaptor proteins that are recognized by molecular motors.
      Current and future research in the neuronal cell polarity will be focused on how
      different cargo molecules transmit their signals to the cytoskeleton and change
      its dynamic properties to affect the rate and direction of vesicular movement. In
      this review, we discuss recent evidence that scaffolding proteins can regulate
      motor motility and guidance by a mechanism of substrate-cytoskeletal coupling and
      amino acid modifications during polarized transport.

PMID- 14704953
TI  - Signaling endosome hypothesis: A cellular mechanism for long distance
      communication.
AB  - The kinetics of signaling endosome retrograde transport along axons is analyzed
      and offered as evidence that such transport is more efficient than diffusion or
      calcium wave-based signaling systems over even relatively small distances.
      Evidence is provided to support the signaling endosome hypothesis and to expand
      the hypothesis to include signaling in many cell types and many cellular
      dimensions. Finally, a saltatory, regenerating inositol 1,4,5-trisphosphate wave
      model is offered to reconcile current discrepancies in the literature regarding
      endosomal-based retrograde signaling.

PMID- 14704954
TI  - Retrograde transport of neurotrophins: fact and function.
AB  - Retrograde signals generated by nerve growth factor (NGF) and other neurotrophins
      promote the survival of appropriately connected neurons during development, and
      failure to obtain sufficient retrograde signals may contribute to neuronal death
      occurring in many neurodegenerative diseases. The discovery over 25 years ago
      that NGF supplied to the axon terminals is retrogradely transported to the cell
      bodies suggested that NGF must reach the cell body to promote neuronal survival.
      Research during the intervening decades has produced a refinement of this
      hypothesis. The current hypothesis is that NGF bound to TrkA at the axon terminal
      is internalized into signaling endosomes, with NGF in their lumens bound to
      phosphorylated TrkA in their membranes, which are retrogradely transported to the
      cell bodies, where TrkA activates downstream signaling molecules that promote
      neuronal survival and regulate many aspects of neuronal gene expression. This
      model has been extrapolated to retrograde signaling by all neurotrophins. We
      consider the evidence for this model, focusing on results of experiments with
      neurons in compartmented cultures. Results to date indicate that while the
      transport of signaling endosomes containing NGF bound to TrkA may carry
      retrograde signals, retrograde survival signals can be carried by another
      mechanism that is activated by NGF at the axon terminal surface and travels to
      the cell body unaccompanied by the NGF that initiated it. It is hypothesized that
      multiple mechanisms of retrograde signaling exist and function under different
      circumstances. The newly discovered potential for redundancy in retrograde
      signaling mechanisms can complicate the interpretation of experimental results.

PMID- 14704955
TI  - What is the importance of multivesicular bodies in retrograde axonal transport in
      vivo?
AB  - Neurons with long axons have a unique problem in generating signaling cascades
      that are able to reach the nucleus after receptor activation by neurotrophins at
      the nerve terminal. The straightforward concept of receptor binding and local
      generation of 2nd second messenger cascades is too simplistic. In this review we
      will outline a mechanism that would enable the complex signals generated at the
      nerve terminal to be conveyed intact to the cell body. There are three different
      sites in the neuron where 2nd messenger proteins can interact with the signaling
      complex and be activated. Signaling cascades are initiated both at the nerve
      terminal and at the cell body when 2nd messengers are recruited to the plasma
      membrane by activated receptors. After receptor-mediated endocytosis, 2nd
      messenger molecules continue to be recruited to the internalized vesicle;
      however, the mix of proteins differs in the nerve terminal and in the cell body.
      At the nerve terminal the activated pathways result in the formation of the
      neurotrophin signaling endosome, which includes molecules to be retrogradely
      transported to the cell body. When the retrograde neurotrophin signaling endosome
      reaches the cell body, it can recruit additional 2nd messenger molecules to
      finally generate the unique signal derived from the nerve terminal. We propose
      that the multivesicular body observed in vivo functions as an endosome carrier
      vehicle or retrosome. This retrosome enables the mix of signaling molecules
      recruited at the terminal to be transported intact to the cell body. This will
      allow the cell body to receive a snapshot of the events occurring at the nerve
      terminal at the time the retrosome is formed.

PMID- 14704956
TI  - Mechanisms of neurotrophin receptor vesicular transport.
AB  - Accumulating evidence has indicated that neurotrophin receptor trafficking plays
      an important role in neurotrophin-mediated signaling in developing as well as
      mature neurons. However, little is known about the molecular mechanisms and the
      components of neurotrophin receptor vesicular transport. This article will
      describe how neurotrophin receptors, Trk and p75 neurotrophin receptor (p75NTR),
      are intimately involved in the axonal transport process. In particular, the
      molecules that may direct Trk receptor trafficking in the axon will be discussed.
      Finally, potential mechanisms by which receptor-containing vesicles link to
      molecular cytoskeletal motors will be presented.

PMID- 14704957
TI  - Cargo-carrying motor vehicles on the neuronal highway: transport pathways and
      neurodegenerative disease.
AB  - Within axons vital cargoes must be transported over great distances along
      microtubule tracks to maintain neuronal viability. Essential to this system are
      the molecular motors, kinesin and dynein, which transport a variety of neuronal
      cargoes. Elucidating the transport pathways, the identity of the cargoes
      transported, and the regulation of motor-cargo complexes are areas of intense
      investigation. Evidence suggests that essential components, including signaling
      proteins, neuroprotective and repair molecules, and vesicular and cytoskeletal
      components are all transported. In addition newly emerging data indicate that
      defects in axonal transport pathways may contribute to the initiation or
      progression of chronic neuronal dysfunction. In this review we concentrate on
      microtubule-based motor proteins, their linkers, and cargoes and discuss how
      factors in the axonal transport pathway contribute to disease states. As
      additional cargo complexes and transport pathways are identified, an
      understanding of the role these pathways play in the development of human disease
      will hopefully lead to new diagnostic and treatment strategies.

PMID- 14704959
TI  - From snails to sciatic nerve: Retrograde injury signaling from axon to soma in
      lesioned neurons.
AB  - The cell body of a lesioned neuron must receive accurate and timely information
      on the site and extent of axonal damage, in order to mount an appropriate
      response. Specific mechanisms must therefore exist to transmit such information
      along the length of the axon from the lesion site to the cell body. Three
      distinct types of signals have been postulated to underlie this process, starting
      with injury-induced discharge of axon potentials, and continuing with two
      distinct types of retrogradely transported macromolecular signals. The latter
      include, on the one hand, an interruption of the normal supply of retrogradely
      transported trophic factors from the target; and on the other hand activated
      proteins emanating from the injury site. These activated proteins are termed
      "positive injury signals", and are thought to be endogenous axoplasmic proteins
      that undergo post-translational modifications at the lesion site upon axotomy,
      which then target them to the retrograde transport system for trafficking to the
      cell body. Here, we summarize the work to date supporting the positive retrograde
      injury signal hypothesis, and provide some new and emerging proteomic data on the
      system. We propose that the retrograde positive injury signals form part of a
      complex that is assembled by a combination of different processes, including post
      translational modifications such as phosphorylation, regulated and transient
      proteolysis, and local axonal protein synthesis.

PMID- 14704958
TI  - Axonal defects in mouse models of motoneuron disease.
AB  - Human motoneuron disease is characterized by loss of motor endplates, axonal
      degeneration, and cell death of motoneurons. The identification of the underlying
      gene defects for familial ALS, spinal muscular atrophy (SMA), and spinal muscular
      atrophy with respiratory distress (SMARD) has pointed to distinct
      pathophysiological mechanisms that are responsible for the various forms of the
      disease. Accumulating evidence from mouse models suggests that enhanced
      vulnerability and sensitivity to proapoptotic stimuli is only responsible for
      some but not all forms of motoneuron disease. Mechanisms that modulate
      microtubule assembly and the axonal transport machinery are defective in several
      spontaneous and ENU (ethylnitrososurea) mutagenized mouse models but also in
      patients with mutations in the p150 subunit of dynactin. Recent evidence suggests
      that axonal growth defects contribute significantly to the pathophysiology of
      spinal muscular atrophy. Reduced levels of the survival motoneuron protein that
      are responsible for SMA lead to disturbed RNA processing in motoneurons. This
      could also affect axonal transport of mRNAs for beta-actin and other proteins
      that play an essential role in axon growth and synaptic function. The local
      translation of specific proteins might be affected, because developing
      motoneurons contain ribosome-like structures in distal axons and growth cones.
      Altogether, the evidence from these mouse models and the new genetic data from
      patients suggest that axon growth and maintenance involves a variety of
      mechanisms, including microtubule assembly and axonal transport of proteins and
      ribonucleoproteins (RNPs). Thus, defects in axon maintenance could play a leading
      role in the development of several forms of human motoneuron disease.

PMID- 14704960
TI  - Axonal transport and neuronal transcytosis of trophic factors, tracers, and
      pathogens.
AB  - Neurons can specifically internalize macromolecules, such as trophic factors,
      lectins, toxins, and other pathogens. Upon internalization in terminals, proteins
      can move retrogradely along axons, or, upon internalization at somatodendritic
      domains, they can move into an anterograde axonal transport pathway. Release of
      internalized proteins from neurons after either retrograde or anterograde axonal
      transport results in transcytosis and trafficking of proteins across multiple
      synapses. Recent studies of binding properties of several such proteins suggest
      that pathogens and lectins may utilize existing transport machineries designed
      for trafficking of trophic factors. Specific pathways may protect trophic
      factors, pathogens, and toxins from degradation after internalization and may
      target the trophic or pathogenic cargo for transcytosis after either retrograde
      or anterograde transport along axons. Elucidating the molecular mechanisms of
      sorting steps and transport pathways will further our understanding of trophic
      signaling and could be relevant for an understanding and possible treatment of
      neurological diseases such as rabies, Alzheimer's disease, and prion
      encephalopathies. At present, our knowledge is remarkably sparse about the types
      of receptors used by pathogens for trafficking, the signals that sort trophins or
      pathogens into recycling or degradation pathways, and the mechanisms that
      regulate their release from somatodendritic domains or axon terminals. This
      review intends to draw attention to potential convergences and parallels in
      trafficking of trophic and pathogenic proteins. It discusses axonal
      transport/trafficking mechanisms that may help to understand and eventually treat
      neurological diseases by targeted drug delivery.

PMID- 14704961
TI  - Peripheral nerve regeneration using acellular nerve grafts.
AB  - Long gap peripheral nerve injuries usually require a graft to facilitate axonal
      regeneration into the distal nerve stump. The use of autografts is often limited
      because of graft availability and donor-site morbidity. We investigated whether
      acellular nerve allografts would provide an appropriate channel for the promotion
      and induction of sciatic nerve regeneration in rats. Axons sprouted from the
      proximal portion and reached the distal portion in the 1 cm-long grafts by 1
      month. The number of axons in the regenerated nerves was similar to that of
      normal nerves at 1 month. Loading the grafts with betaNGF and VEGF increased the
      number and mean diameter of axons and neovascularization in the regenerated
      nerves at 1 month. The motor conduction velocity increased over time and reached
      63 +/- 10% of that of normal nerves at 6 months. The nerve injuries treated with
      the acellular grafts had a significant improvement in motor, nociception, and
      proprioception function compared to untreated nerves. The results from this study
      suggest that acellular nerve allografts may be a useful biomaterial for
      functional peripheral nerve regeneration.

PMID- 14704962
TI  - Effect of composition of interpenetrating polymer network hydrogels based on
      poly(acrylic acid) and gelatin on tissue response: a quantitative in vivo study.
AB  - The local tissue response of the biomaterial is the most important criteria for
      determination of its biocompatibility. In the present study, full and semi
      interpenetrating polymer networks (IPN) based on polyacrylic acid (AAc) and
      gelatin (Ge) crosslinked with 0.5 mol % N,N'-methylene bisacrylamide (BAm) and 4%
      glutaraldehyde (GA), respectively, were evaluated for tissue response in rats.
      IPNs with varying ratios of AAc and Ge were implanted subcutaneously in rats.
      Gentamicin sulfate (GS)-loaded IPN samples were also studied to evaluate the
      possible therapeutic use of these polymers. The site of implantation was biopsied
      and processed for light microscopy (LM) with image analysis for assessment of
      tissue reaction at 2-, 6-, and 12-week intervals. The tissue reaction was
      evaluated as a function of composition and time. The degree of neutrophil,
      lymphocyte and macrophage infiltration, fibrosis, granuloma formation,
      integration with extracellular matrix, vascular proliferation, and damage of
      adjacent structures were assessed. Polymers with >66% crosslinked Ge (Gx) showed
      persistence of acute inflammatory reaction till 3 months, with marked tissue
      injury and fibrosis. On the other hand, high crosslinked AAc (Ax) content showed
      chronic inflammatory reaction with high macrophage infiltration. Macrophages took
      active part in phagocytosis, degradation, and removal of polymers without
      granuloma formation or significant giant cell reaction. The IPNs with acrylic
      acid and gelatin in the ratio of 1:1 showed least tissue reaction and thus
      appeared to be most biocompatible. The majority of the polymers showed
      integration with extracellular matrix and growth of capillaries in and around the
      polymer. The heamogram, liver and renal function tests, and histology of vital
      organs were all normal. GS loading showed no additional local or systemic
      reaction suggesting the potential usefulness of the hydrogels as carrier for
      drugs such as GS.

PMID- 14704963
TI  - Carboxymethylcellulose-stabilized collagenous rhOP-1 device-a novel carrier
      biomaterial for the repair of mandibular continuity defects.
AB  - Human recombinant osteogenic protein-1 (rhOP-1) is osteoinductive. Efforts are
      made to develop carrier biomaterials with improved space-keeping properties.
      Bovine collagen type I matrix charged with rhOP-1 was suggested to be an
      advantageous device of relative liquid quality. We hypothesized that the addition
      of carboxymethylcellulose (CMC) may stabilize the device and facilitate the
      regeneration of mandibular continuity defects without further addition of
      mineralized carrier materials. To test this hypothesis, the anatomical shape,
      functional remodeling, and mechanical stability of such bony regenerates were
      evaluated in the course of an animal experiment. Mandibular continuity defects of
      5 cm in size were created in five Gottingen minipigs on one side (contralateral
      hemimandible: control) and bridged with titanium plates. Four animals were
      treated with the rhOP-1 device (3000 microg rhOP-1, 2 g collagen, 1 g CMC), and
      one animal was treated with a placebo device omitting rhOP-1. After 12 weeks of
      experimental period, bony continuity was reestablished in rhOP-1-treated
      hemimandibles. The bony regenerates were of good anatomical shape, volume, and
      functional remodeling. Placebo treatment led to insufficient bony regenerates of
      significant lower bone volume (volume in 3D-CT scan 29.81 cm(3) vs 8.85 cm(3)).
      To produce 1 mm of bending, 1972 N were needed for rhOP-1-treated hemimandibles,
      2617 N for control hemimandibles, and 642 N for the placebo treated hemimandible.
      CMC stabilization of collagen carrier biomaterials for rhOP-1 provides good
      plasticity as well as excellent space-keeping properties and may not interfere
      with osteoinduction. The results of this preliminary study suggest that the
      applied rhOP-1 device offers a potential option for further studies on the
      reconstruction of mandibular defects.

PMID- 14704964
TI  - Effects of multigrooved surfaces on osteoblast-like cells in vitro: scanning
      electron microscopic observation and mRNA expression of osteopontin and
      osteocalcin.
AB  - This study evaluated the behavior of osteoblast-like cells on multigrooved
      surfaces consisting of a combination of microgrooves and macrogrooves. A
      polystyrene substrate was fabricated with multigrooves with 90-degree, V-shaped
      microgrooves with a 2-microm pitch cut on trapezoidal macrogrooves, which had a
      50-microm ridge width, a 50-microm wall width, a 50-microm bottom width, and 25
      microm depth. Smooth polystyrene substrates were also prepared as controls. Rat
      bone marrow cells were cultured as osteoblast-like cells on the substrates for
      morphological evaluation using a scanning electron microscope, and for
      biochemical evaluation using the quantitative reverse transcriptase-polymerase
      chain reaction technique for osteopontin and osteocalcin mRNA expression. After 8
      days of incubation, the osteoblast-like cells were aligned parallel to the
      surface grooves on the multigrooved substrates. After 16 days of incubation, a
      dense mineralized extracellular matrix (ECM) was produced along the multigrooves.
      The ECM on the multigrooved surface appeared oriented more in the direction of
      the grooves than on the smooth surface, and trapezoid-shaped macrogrooves of the
      ECM were cast upside down. Although there were not significant differences, the
      osteopontin and osteocalcin mRNA expressions of the osteoblast-like cells on the
      multigrooved surfaces tended to be higher than on smooth surfaces. These results
      suggest that multigrooves could be used to control the orientation of mineralized
      ECM as well as of cells, and also to enhance the production of mineralized ECM.

PMID- 14704965
TI  - Immobilized concentration gradients of nerve growth factor guide neurite
      outgrowth.
AB  - Axons are guided to their targets by a combination of haptotactic and chemotactic
      cues. We previously demonstrated that soluble neurotrophic factor concentration
      gradients guide axons in a model system. In an attempt to translate this model
      system to a device for implantation, our goal was to immobilize a stable
      neurotrophic concentration gradient for axonal (or neurite) guidance. Nerve
      growth factor (NGF) was immobilized within poly(2-hydroxyethylmethacrylate)
      [p(HEMA)] microporous gels using a gradient maker. The NGF was stably
      immobilized, with only approximately 0.05% of the amount originally incorporated
      into the gel released over an 8-day period. Immobilized NGF was bioactive: the
      percent of PC12 cells extending neurites on NGF-immobilized p(HEMA) gels was 16
      +/- 2%, which was statistically the same as those exposed to soluble NGF (22 +/-
      6%). We were able to predict and reproducibly create stable NGF concentration
      gradients in the gel. At an NGF concentration gradient of 357 ng/mL/mm, PC12 cell
      neurites were guided up the gradient. The facile, flexible, and reproducible
      nature of this method allowed us to translate soluble growth factor gradient
      models to stable growth factor gradient devices that may ultimately enhance
      axonal guidance and regeneration in vivo.

PMID- 14704966
TI  - Cytotoxicity evaluation of ceramic particles of different sizes and shapes.
AB  - When artificial hip or knee joints are implanted in the human body, they release
      metallic, ceramic, and polymeric debris into the surrounding tissues. The
      toxicity of the released particles is of two types: chemical, caused by the
      released soluble ions and monomers, and mechanical, a result of mechanical
      stimulation produced by the insoluble particles. In this study, the cytotoxicity
      of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and
      macrophages were examined to evaluate just their mechanical toxicity because
      these particles are not expected to release soluble metal ions. Different sizes
      and shapes of TiO2 particles were used to evaluate the effect of size and shape
      on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic
      particles does not depend on their chemical species. Cytotoxicity levels were
      lower than those of corresponding metal ions, indicating that the mechanical
      toxicity of particles is lower than the chemical toxicity of released soluble
      ions and monomers. The differences in size did not affect the mechanical toxicity
      of these particles. The dendritic particles had a higher cytotoxicity level for
      macrophages than did spindle and spheric particles.

PMID- 14704967
TI  - Gingival organotypic culture and langerhans cells: a tool for immunotoxicologic
      experiments.
AB  - Langerhans cells (LCs) are dendritic cells localized in epidermis and mucosal
      tissues, where they are responsible for triggering the immune response. To study
      LCs in the oral epithelium, organotypic cultures were prepared using gingival
      explants. Immunochemical techniques using anti-CD1a, anti-HLA-DR, and anti
      Langerin antibodies were used to detect and quantify LCs at various times.
      Observations were made by light and confocal microscopy. Quantification studies
      showed that there is a statistically significant drop in LC numbers in the
      epithelial tissue after 96 h of incubation. Gingival organotypic cultures thus
      are a good model for studying the migration of LCs and their involvement in
      contact hypersensitivity and periodontal diseases. The model offers potential
      utility as a tool for the study of periodontal tissue in the presence of
      different stimuli and for conducting immunotoxicologic experiments.

PMID- 14704968
TI  - Osteointegration of bioactive glass-coated and uncoated zirconia in osteopenic
      bone: an in vivo experimental study.
AB  - In elderly and osteoporotic patients an age-related loss of osteoinductivity
      could be the biological cause of implant failure regardless of the high quality
      of the implanted device. yttria stabilized tetragonal zirconia (YSTZ), either
      coated with the bioactive glass named RKKP bioglaze (RKKP) or uncoated, was
      implanted in the distal femurs of sham-operated and ovariectomized female rats.
      Animals were sacrificed at 30 and 60 days. Histomorphometry and microhardness
      tests were performed to assess osteointegration rate as well as bone quality
      around the implants. Significant decreases (p < 0.0005) in trabecular bone
      volume, BV/TV (41%), trabecular bone surface BS/TV (33%), trabecular thickness
      Tb.Th (20%), and trabecular number Tb.N (32%), together with a significant
      increase in trabecular separation Tb.Sp (184%), were found for the osteopenic
      rats compared with the sham-operated rats. At both experimental times the RKKP
      coating ensured a better osteointegration rate with higher AI values than the
      uncoated YSTZ, even when osteopenic rats were used (48% at 30 days and 12% at 60
      days). No differences were observed at the bone-biomaterial interfaces for either
      material when comparing sham-operated with osteopenic rats. The present results
      demonstrate that the RKKP bioactive glass used as a coating ensures a high
      osteointegration rate even in osteoporotic bone, which is already visible from
      postoperative day 30 and is still apparent on day 60.

PMID- 14704969
TI  - Primary human marrow stromal cells and Saos-2 osteosarcoma cells use different
      mechanisms to adhere to hydroxylapatite.
AB  - One important step in bone formation on hard tissue implants is adhesion of
      osteoblast precursors to the implant surface. In this study, we used function
      blocking antibodies against integrin subunits to characterize the mechanisms used
      by human marrow stromal cells and Saos-2 osteosarcoma cells to adhere to protein
      coated hydroxylapatite (HA). We found that Saos-2 use both alpha5- and alphav
      containing integrins, whereas stromal cells use alphav-containing integrins but
      not alpha5-containing integrins, despite the presence of alpha5-containing
      integrins on cell surfaces. On the basis of this difference, we examined binding
      of these cell types to HA coated with fibronectin (FN) or vitronectin (VN), to
      determine whether these ligands for alpha5 and alphav integrins could enhance the
      numbers or morphology of cells adhered to them. We also examined the adhesion of
      cells to HA coated with RGD peptides designed to bind to FN or VN receptors.
      Morphology and number of adherent stromal cells were markedly enhanced on serum
      coated surfaces compared with FN or VN alone, whereas, surprisingly, Saos-2 cells
      failed to spread on serum-coated HA and displayed superior spreading and stress
      fiber formation on FN-coated [corrected] HA. Collectively, these results have
      important implications for the design of protein coatings to enhance the
      performance of HA implants.

PMID- 14704970
TI  - Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide)
      biodegradable polymer fibers.
AB  - Tiny tubes with fiber architecture were developed by a novel method of
      fabrication upon introducing some modification to the microbraiding technique, to
      function as nerve guide conduit and the feasibility of in vivo nerve regeneration
      was investigated through several of these conduits. Poly(L-lactide-co-glycolide)
      (10:90) polymer fibers being biocompatible and biodegradable were used for the
      fabrication of the conduits. The microbraided nerve guide conduits (MNGCs) were
      characterized using scanning electron microscopy to study the surface morphology
      and fiber arrangement. Degradation tests were performed and the micrographs of
      the conduit showed that the degradation of the conduit is by fiber breakage
      indicating bulk hydrolysis of the polymer. Biological performances of the
      conduits were examined in the rat sciatic nerve model with a 12-mm gap. After
      implantation of the MNGC to the right sciatic nerve of the rat, there was no
      inflammatory response. One week after implantation, a thin tissue capsule was
      formed on the outer surface of the conduit, indicating good biological response
      of the conduit. Fibrin matrix cable formation was seen inside the MNGC after 1
      week implantation. One month after implantation, 9 of 10 rats showed successful
      nerve regeneration. None of the implanted tubes showed tube breakage. The MNGCs
      were flexible, permeable, and showed no swelling apart from its other advantages.
      Thus, these new poly(L-lactide-co-glycolide) microbraided conduits can be
      effective aids for nerve regeneration and repair and may lead to clinical
      applications.

PMID- 14704971
TI  - Fibroblast attachment to smooth and microtextured PET and thin cp-Ti films.
AB  - Improving the biological performance of engineered implants apposing interfacing
      tissues is a critical issue in Biomaterials Science and Engineering. Micromotion
      at the soft tissue-implant interface has been shown to sustain an inflammatory
      response. To eliminate micromotion, it is desirable to promote cellular and
      extracellular matrix adhesion to the implant surface. Surfaces are modified
      topographically or chemically to effect cellular adhesion and to influence
      cellular interactions and function. Previous studies have identified the specific
      topographical characteristics that appear to elicit cellular attachment. This in
      vitro study compares the independent effects of surface chemistry and topography
      on fibroblast-test specimen proximity. Titanium (Ti) was sputter-coated in
      stepwise, increasing thickness (20-350 nm) onto a series of either smooth or
      microtextured polyethylene terephthalate (PET), resulting in a stepwise change
      from a PET surface to a Ti surface. The series was evaluated in a 3-day
      fibroblast culture with transmission electron microscopy (TEM) for cell-test
      specimen proximity. Fibroblast proximity to the coverslip surface increases, as
      the Ti thickness increases, on either smooth or textured test specimens.
      Furthermore, fibroblasts were firmly attached to the ridge tops on the coated
      textured test specimens. Therefore, fibroblast apposition is strongly enhanced by
      microtextured surfaces and Ti rather than smooth surfaces and PET.

PMID- 14704972
TI  - Use of an intramedullary in vivo model to study bone formation and maintenance in
      ceramic porous domains.
AB  - Tissue ingrowth, differentiation, and osteogenesis in a porous bioinert
      bioceramic were studied using an intramedullary model. Pure alumina tubes (1.3 mm
      outer diameter, 0.6 mm inner diameter, 15 mm length) were implanted in the
      femoral medullary canal of young female rats for 4, 6, 8, 12, and 16 weeks.
      Tissues present within each tube were characterized by histology and quantified
      by histomorphometry. A tissue front consisting of undifferentiated mesenchymal
      cells, fibrovascular tissue, osteoid, woven bone, and marrow penetrated the tube
      from both ends. Behind the front, woven bone remodeled to produce a thin layer of
      lamellar bone that lined the tube walls the entire distance to the tube ends and
      enclosed a marrow-filled lumen. The front was considered to represent the
      differentiation cascade from mesenchymal cells to fibrovascular tissue to osteoid
      to woven bone and marrow to lamellar bone and marrow. The fronts advanced into
      the tube with time such that, by 16 weeks, they were close to meeting or had met.
      In several instances, the tube was completely lined with a thin layer of mature
      lamellar bone continuous between the two ends and enclosing marrow. This
      configuration was considered to be the final equilibrium of tissues within the
      tube.

PMID- 14704973
TI  - Substrate-dependent cellular behavior of Swiss 3T3 fibroblasts and activation of
      Rho family during adhesion and spreading processes.
AB  - Recent biochemical studies revealed that intracellular Rho guanosine
      triphosphatases (Rho, Rac1, and Cdc42) are key regulatory molecules that link
      surface receptors to cytoskeletal organization and regulation of cell
      shape/morphology/motility. In this study, Swiss 3T3 fibroblasts were cultured on
      three representative substrates [tissue culture polystyrene dishes, nontreated
      polystyrene, and poly(ethylene terephthalate)] for 24 h after plating. Time
      dependent changes in cell shape, morphology, cytoskeletal dynamics, and motility
      as well as Rho family activities were determined on each substrate. The cells on
      tissue culture polystyrene and on poly(ethylene terephthalate), which induced
      rapid and relatively rapid cell spreading, respectively, expressed Rac1 and Cdc42
      activities continuously during the observation period. In contrast, such
      activities were suppressed in cells on polystyrene, which induced slow spreading
      but the highest cell motility compared with the other two substrates. Although a
      clear-cut relationship between cellular behavior and Rho family activation was
      not obtained, substrate-dependent coordinated control of cellular activities by
      Rho family is discussed.

PMID- 14704974
TI  - Growth behavior, matrix production, and gene expression of human osteoblasts in
      defined cylindrical titanium channels.
AB  - The purpose of the current study was to investigate the effect of different
      diameters of cylindrical titanium channels on human osteoblasts. Titanium samples
      having continuous drill channels with diameters of 300, 400, 500, 600, and 1000
      microm were put into osteoblast cell cultures that were isolated from 12 adult
      human trauma patients. Cell migration into the drill channels was investigated by
      transmitted-light microscopy. The DNA content in the drill channels was measured
      photometrically, collagen type I production was analyzed by enzyme-linked
      immunosorbent assay (ELISA) and osteocalcin gene expression by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Formation of mineralized tissue
      was assessed by microradiographs of histological sections. Within 20 days, cells
      grew an average of 838 microm (+/-128 microm) into the drill channels with a
      diameter of 600 microm and were significantly faster (p < 0.05) than in all other
      channels. Cells produced significantly more osteocalcin messenger RNA (mRNA) in
      600-microm channels (p < 0.05) than they did in 1000-microm channels and
      demonstrated the highest osteogenic differentiation. The channel diameter did not
      influence collagen type I production. The highest cell density was found in 300
      microm channels (p < 0.05). The DNA content of the channels linearly decreased
      with increasing channel diameters. After 40 days of culture, the proportion of
      mineralized tissue at the mouth section amounted to 6% in 300-microm channels and
      to 9-11% in 400-600-microm channels. In 1000-microm channels, only traces of
      mineralization were detected. Our data suggest that the diameter of cylindrical
      titanium channels has a significant effect on migration, gene expression, and
      mineralization of human osteoblasts.

PMID- 14704975
TI  - Production of microspheres based on hydrophobically associating alginate
      derivatives by dispersion/gelation in aqueous sodium chloride solutions.
AB  - A new "all aqueous" procedure for the preparation of stable polysaccharide
      microparticles was developed. The method consists of dispersing a water solution
      of an amphiphilic alginate derivative (in the current work, alginate substituted
      with low amounts of dodecyl chains) first fluidified under mechanical stress,
      into an NaCl solution. The procedure exploits the ability of amphiphilic
      associative derivatives to form strong hydrogels in the presence of nonchaotropic
      salts and their shear-thinning/thixotropic properties. Depending on the
      experimental conditions, the size of the microparticles can be varied from 10
      microm to several hundred micrometers. Their mechanical properties can eventually
      be reinforced by addition of low concentrations of calcium chloride. The
      resulting microparticles exhibit a better stability than that of plain Ca(2+)
      alginate particles, as they are not disrupted when nongelling cations or calcium
      sequestering agents are added to the solution. In addition, the particles can be
      easily redispersed after being centrifuged or freeze-dried.

PMID- 14704976
TI  - Ultrastructure and nanomechanical properties of cementum dentin junction.
AB  - The attachment between cementum and dentin has been given several definitions and
      nomenclature, including: interzonal layer, intermediate cementum, collagen
      hiatus, Hopewell-Smith's hyaline layer, and more commonly, cementum-dentin
      junction (CDJ). Understanding the attachment of two structurally dissimilar hard
      tissues such as cementum and dentin defined by a junction may provide information
      necessary to engineer functionally graded materials that can be used for
      efficient tooth restorations in clinical dentistry and other bioengineering
      applications. Hence, in this study, as a first step toward understanding the CDJ
      using a biomechanical approach, it was hypothesized that the CDJ between cementum
      and dentin is a wide zone with mechanical properties significantly lower than the
      neighboring tissues. The structure of the CDJ was studied using an atomic force
      microscope (AFM), and site-specific mechanical response of the three regions;
      cementum, CDJ, and dentin were determined using an AFM-nanoindenter under dry and
      wet conditions. The AFM results of the CDJ demonstrated a valley under dry
      conditions and a peak under wet conditions. The magnitude of the depth of the
      valley was approximately the same as the height of the peak of the CDJ, ranging
      from 10 to 40 microm. The nanomechanical properties under dry conditions
      indicated no significant difference (p > 0.05) in elastic modulus and hardness of
      the CDJ (Er = 17.5 +/- 2.7 GPa, H = 0.6 +/- 0.1 GPa) and cementum (Er = 18.7 +/-
      2.5 GPa, H = 0.6 +/- 0.1 GPa). The mechanical properties of the CDJ were
      significantly lower (p << 0.05) than dentin (Er = 19.9 +/- 2.9 GPa, H = 0.6 +/-
      0.1 GPa) under dry conditions. However, under more relevant hydrated conditions,
      the mechanical properties of CDJ (Er 3.0 +/- 0.7 GPa, H = 0.1 +/- 0.0 GPa) were
      significantly lower (p << 0.05) than those of cementum (Er 6.8 +/- 1.9 GPa, H =
      0.2 +/- 0.1 GPa) and dentin (Er 9.4 +/- 2.3 GPa, H = 0.3 +/- 0.1 GPa). Based on
      the results from this study, it can be concluded that the CDJ can be regarded as
      a wide zone containing large quantities of proteins including collagen that
      contribute to hydration and significantly reduce mechanical properties, compared
      with the adjacent hard tissues, cementum, and dentin. The lower mechanical
      properties of the CDJ may make it possible for it to redistribute occlusal loads
      to the alveolar bone.

PMID- 14704977
TI  - Fibronectin interactions with osteoblasts: identification of a non-integrin
      mediated binding mechanism using a real-time fluorescence binding assay.
AB  - Fibronectin (Fn) is an extracellular matrix protein that interacts with specific
      integrins on the cell surface, initiating signal transduction processes that lead
      to a reorganization of the cytoskeleton and the assembly of focal adhesions. Cell
      surface proteoglycans or glycosaminoglycans (GAGs) such as heparan sulfate are
      also known to participate in the interaction of Fn with the cell surface by
      binding to two different heparin-binding domains. The influence of Fn and GAGs on
      the spreading and differentiation of human osteoblasts was also previously
      described. In the current work, a method developed in our laboratory is
      established to evaluate the interaction between Fn and human osteoblasts and the
      influence of GAGs on such interactions. This technique makes use of
      fluoresceinphosphatidylethanolamine (FPE) such that when inserted into the
      lipidic bilayer, it acts as a fluorescent indicator of membrane interactions. The
      results indicate that the binding profile of Fn with the osteoblast cell surface
      is best represented by a hyperbolic single binding site model with a membrane
      affinity of 120 nM. Removal of cell surface heparan sulfate by treatment with
      heparitinase indicates that the cell surface moiety is directly involved in the
      binding process. Studies directed to assess the influence of heparin on the
      interaction of Fn with osteoblasts reveal that although it does not hamper Fn
      binding to the cell surface, it blocks the initial attachment to Fn-coated
      surfaces, indicating that binding to the integrin receptor alone is not enough to
      promote cell attachment but that the participation of the cell-surface GAGs is
      also a necessary condition.

PMID- 14704978
TI  - Pitfalls in the detection of lipid vectors in neural cell culture and in brain
      tissue.
AB  - Lipid particles (liposomes and lipid-coated microbubbles) are currently studied
      as vectors for drug delivery to the central nervous system. The visualization of
      these particles is usually based on their labeling with a lipophilic fluorescent
      dye (3,3'-dioctadecycloxacarbocyanine perchlorate) or staining with Oil Red O.
      The purpose of this article was to highlight the difficulties and pitfalls
      encountered with the use of these techniques in the detection of lipid particles
      in neural cell cultures and in brain tissue. In vitro and in vivo studies were
      conducted on different neural cell cultures (rat and human tumors, microglial
      cells) and animal models of brain lesion (lipopolysaccharide and quinolinic acid
      induced lesion, induced brain tumor). The cells or brain slices were observed
      with optical microscopy after staining with Oil Red O, fluorescent microscopy, or
      scanning electron microscopy. Intra and extracytoplasmic lipid particles (stained
      with Oil Red O or autofluorescent or visualized by scanning electron microscopy)
      were naturally found in the cells and tissues studied. Intracytoplasmic lipid
      microparticles were present in tumoral and microglial cells. These lipid
      microparticles were also observed with some extracytoplasmic lipid droplets in
      the induced brain lesions. These images could be misinterpreted as lipid vectors
      if the cells or animals would have been treated with such a vector.

PMID- 14704979
TI  - Attachment and spreading of fibroblasts on an RGD peptide-modified injectable
      hyaluronan hydrogel.
AB  - Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts and most
      other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic
      dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp
      (RGD) sequence and then crosslinked with polyethylene glycol (PEG) diacrylate
      (PEGDA) to create a biomaterial that supported cell attachment, spreading, and
      proliferation. The hydrogels were evaluated in vitro and in vivo in three assay
      systems. First, the behavior of human and murine fibroblasts on the surface of
      the hydrogels was evaluated. The concentration and structure of the RGD peptides
      and the length of the PEG spacer influenced cell attachment and spreading.
      Second, murine fibroblasts were seeded into HA-DTPH solutions and encapsulated
      via in situ crosslinking with or without bound RGD peptides. Cells remained
      viable and proliferated within the hydrogel for 15 days in vitro. Although the
      RGD peptides significantly enhanced cell proliferation on the hydrogel surface,
      the cell proliferation inside the hydrogel in vitro was increased only modestly.
      Third, HA-DTPH/PEGDA/peptide hydrogels were evaluated as injectable tissue
      engineering materials in vivo. A suspension of murine fibroblasts in HA-DTPH was
      crosslinked using PEGDA plus PEGDA peptide, and the viscous, gelling mixture was
      injected subcutaneously into the flanks of nude mice; gels formed in vivo
      following injection. After 4 weeks, growth of new fibrous tissue had been
      accelerated by the sense RGD peptides. Thus, attachment, spreading, and
      proliferation of cells is dramatically enhanced on RGD-modified surfaces but only
      modestly accelerated in vivo tissue formation.

PMID- 14704980
TI  - Gene expression changes in BALB/3T3 transformants induced by poly(L-lactic acid)
      or polyurethane films.
AB  - We performed DNA microarray analysis on two BALB/3T3 transformants (A5 and A6)
      induced by polyurethane (PU) film, two (L11 and L21) induced by biodegradable
      poly(L-lactic acid) (PLLA) film, and the parental cells. The transforming ability
      of the cells was in the order A5 < A6 < L21 < L11. In all, 1176 cancer-related
      genes were up- or down-regulated in at least one transformant. Those that were
      markedly up-regulated were c-fos protooncogene, FBJ osteosarcoma oncogene B, and
      Jun oncogene; those markedly down-regulated were pleiotrophin, histidine triad
      nucleotide-binding protein, protein kinase C iota, and large multifunctional
      protease 7. A common function of proteins encoded by genes that underwent marked
      expression changes was bone formation. The genes were c-fos, FBJ osteosarcoma,
      Jun, pleiotrophin, a disintegrin-like and metalloprotease with TS-1 motif protein
      1. This finding was consistent with the tumor formation in the 2-year PLLA or PU
      subcutaneous implantation into rats. The number of genes that underwent marked
      expression change in each transformant was consistent with its malignancy. PLLA
      induced more malignant transformants than PU, especially in relation to
      osteosarcoma-like gene expression.

PMID- 14704981
TI  - Surface analyses of micro-arc oxidized and hydrothermally treated titanium and
      effect on osteoblast behavior.
AB  - Osteoblast adhesion on the implant material surface is essential for the success
      of any implant in which osteointegration is required. Surface properties of
      implant material have a critical role in the cell adhesion progress. Titanium and
      its alloys are widespread and increasingly used as implant material in dentistry
      and orthopedics because of their excellent biocompatibility, which is attributed
      to a passive layer of TiO2 on the surface. In this study, the micro-arc oxidizing
      (MAO) and hydrothermally synthesizing (HS) methods were used to modify the TiO2
      layer on the titanium surface. The surface microstructure was observed by
      scanning electron microscopy. The surface energy was assessed. The mouse
      osteoblastic cell line (MC3T3-E1) was seeded on the treated surfaces to evaluate
      their effect on cell behavior. This included cell adhesion kinetics, cell
      proliferation, cell morphology, and cytoskeletal organization. The surface
      structure of MAO samples exhibited micropores with a diameter of 1-3 microm,
      whereas the MAO-HS-treated samples showed additional multiple crystalline
      microparticles on the microporous surface. The surface energy of MAO and MAO-HS
      was higher than that of titanium. The cell adhesion rate was higher on the MAO-HS
      surface than on the MAO and titanium surface, but without any significant
      difference between them. After 3 days of culture, cells proliferated
      significantly more on the MAO and titanium surface than on the MAO-HS surface.
      The cytoskeletal organization was analyzed by actin and vinculin staining on all
      the samples. We conclude that the MAO and MAO-HS methods change the surface
      energy of TiO2 layer on the titanium surface. This may have an influence on the
      initial cell attachment. Other surface characteristics may be involved in the
      cell proliferation, which is different from cell attachment on the sample
      surface. A longer-duration cell experiment should be conducted to see the effect
      on cell differentiation. Future in vivo evaluation may give further evidence to
      optimize the surface character of this kind of implant material.

PMID- 14704982
TI  - Tissue adhesiveness and host response of in situ photopolymerizable
      interpenetrating networks containing methylprednisolone acetate.
AB  - Interpenetrating networks (IPNs) of varying formulations were investigated as
      candidates for an in situ photopolymerizable drug delivery matrix containing
      poly(ethylene glycol) diacrylate and gelatin. The anti-inflammatory agent
      methylprednisolone acetate was loaded into the IPN. Bond strength between the IPN
      and tissue (i.e., muscle, dermis, skin) was determined by a modified American
      Society for Testing and Materials peel test at constant peel rate. The IPNs
      provided adhesion values of up to 5.7N, which were three- to fivefold lower than
      that of the commercial tissue bioadhesive. The subcutaneous cage implant system
      was utilized to assess material host response and drug efficacy in vivo. IPN
      formulations elicited a more intense acute inflammatory response than the empty
      cage controls. Methylprednisolone acetate loaded within the IPNs lowered the
      level of inflammatory response to levels that were comparable to the empty cage
      baseline controls. In conclusion, a methodology was developed to quantify the
      tissue adhesiveness of an in situ photopolymerized IPN matrix containing anti
      inflammatory agents. The efficacy of drug-loaded IPN in affecting the host
      inflammatory response was demonstrated in vivo.

PMID- 14704983
TI  - Comparative psychology, a new perspective for the 21st century: up the spiral
      staircase.
AB  - This article responds to the continuing obituaries for Comparative Psychology. We
      understand the field to be a general psychology, a way of understanding the
      origins of all behavior of all species. We outline a methodological and
      conceptual foundation for comparative psychology to enter the new millennium-with
      an anagenetic and dynamic systems perspective. We see an important role to be
      played by comparative psychologists in managing resources, increasing our
      activity in social and political issues, and transcending our traditional role as
      the study of animal behavior to one that makes significant contributions to
      psychology and humanity by studying relationships between animals and changing
      environments, and by providing a historical perspective on human evolution.

PMID- 14704984
TI  - Can behavioral evolution be measured on a staircase? A commentary.
AB  - The serious, comparative study of behavioral complexity that Greenberg et al.
      advocate is a progressive direction for the field, but their proposal to separate
      comparative psychology from its roots in evolutionary biology seems regressive.
      Modern evolutionary theory has been broadened within biology to include
      development and paleontology alongside natural selection, making closer
      integration with that discipline particularly timely. Such an integrated
      evolutionary approach in psychology would offer a useful alternative to the
      adaptationism popularized by evolutionary psychology. Although the differences
      between comparative psychologists and biologists may be blurred in the process,
      the behavioral sciences will be better served by a rich biological approach to
      evolution than by a uniquely psychological approach.

PMID- 14704985
TI  - Comparative psychology is still alive but may be losing relevance.
AB  - Greenberg et al., in their perspective on the current state and fate of
      comparative psychology, present convincing data that the field is viable and that
      comparative psychologists are making important contributions to the research
      literature. The central feature of the field is its emphasis upon evolution. This
      is also its weakness since advances in genetic techniques permit researchers to
      create laboratory animals that have no counterpart in the natural world, and thus
      have no evolutionary history. These "unnatural" animals are widely used in
      behavioral, biological, and medical studies, but the findings cannot be
      interpreted within a comparative psychology framework. As the use of these
      preparations expand, the relevance of comparative psychology diminishes.

PMID- 14704986
TI  - The aims and accomplishments of comparative psychology.
AB  - Greenberg, Partridge, Weiss, and Pisula propose a new perspective of comparative
      psychology, based in large part on an anagenetic and dynamic systems approach to
      the development and evolution of behavior. Their view appreciates the
      probabilistic nature of behavioral development and promotes the value of an
      integrative levels concept for generating testable hypothesis regarding the
      complex relationship between biology, context, and developmental history
      underlying behavioral and psychological functioning. However, the authors fail to
      represent the full scope of contemporary comparative psychology by overlooking
      several core aims of the field, including (a) the use of animal models to shed
      light on human behavior and development and (b) understanding the role of
      behavior as a leading edge in the evolutionary process.

PMID- 14704988
TI  - Neonatal behaviors associated with ultrasonic vocalizations in mice (mus
      musculus): A slow-motion analysis.
AB  - Infant rodents emit ultrasonic vocalizations (USVs) when isolated from the mother
      and littermates. While USVs reportedly promote maternal behavior, their
      communicatory role is still controversial. We performed a detailed behavioral
      characterization in 7-day-old CD-1 Swiss mice to describe (a) behavioral patterns
      accompanying or immediately preceding or following the USV and (b) how selected
      USV features are modulated according to the behavioral pattern being performed.
      The present results represent an ethogram of mouse pup behavior in close temporal
      proximity to USV, providing further information to evaluate the functional role
      of USVs in the framework of the mother-offspring relationship. A significant
      increase of head rising behavior immediately prior to the USV and a behavioral
      activation displayed by pups in conjunction with it suggest that pups behave in a
      way that may favor interaction with their mothers.

PMID- 14704989
TI  - Developmental changes in eyeblink conditioning and simple spike activity in the
      cerebellar cortex.
AB  - The activity of neurons in the cerebellum exhibits learning-related changes
      during eyeblink conditioning in adult mammals. The induction and preservation of
      learning-related changes in cerebellar neuronal activity in developing rats may
      be affected by the level of maturity in cerebellar feedback to its brainstem
      afferents, including the inferior olive. Developmental changes in cerebellar
      plasticity were examined by recording the activity of Purkinje cells in eye
      regions of cerebellar cortical lobule HVI (lobulus simplex) in infant rats during
      eyeblink conditioning. The percentage and amplitude of eyeblink conditioned
      responses increased as a function of age. Analyses of Purkinje cell simple spike
      activity revealed developmental increases in the number of units that exhibited
      stimulus-evoked and learning-related changes in activity. Moreover, the magnitude
      of these changes exhibited a substantial age-related increase. The results
      support the view that the emergence of learning-specific cerebellar plasticity
      and the ontogeny of eyeblink conditioning are influenced by developmental changes
      in the synaptic interactions within brainstem-cerebellum circuits.

PMID- 14704990
TI  - Play deprivation without social isolation: housing controls.
AB  - Three experiments were conducted to control for the effects of housing conditions
      during play deprivation on subsequent play rebound in periadolescent rats. To
      address play deprivation without the confound of social isolation, in Experiment
      1, pairs of subjects were housed either in cages divided by wire mesh that
      allowed for olfactory, visual, auditory, and tactile interactions with a same-sex
      age-mate but prevented rough and tumble play or in standard cages. Running wheels
      were provided to similarly housed subjects in Experiment 2 to control for the
      ability to engage in physical activity. In Experiment 3, standard and brooder
      cages were used to control for the effects of housing area. Play-deprived
      subjects in all conditions showed a greatly increased number of play responses
      immediately following deprivation. The results from these experiments more
      clearly indicate that the absence of play is the crucial feature that brings
      about play rebound following deprivation.

PMID- 14704991
TI  - Working memory and inhibitory control in early childhood: Contributions from
      physiology, temperament, and language.
AB  - This study examined the cognitive skills of working memory and inhibitory control
      (WMIC) in relation to physiological functioning, temperament, and language in
      early childhood. WMIC skills were assessed in twenty-five 4 1/2-year-old children
      using the day--night Stroop-like task and the yes--no task; each task required
      the child to remember two rules and to inhibit a dominant response.
      Electroencephalogram (EEG) and heart period (HP) were recorded during baseline
      and WMIC tasks. An increase in 6- to 9-Hz EEG power from baseline to task was
      found for the medial frontal region. In addition, a decrease in HP (i.e., an
      increase in heart rate) was found from baseline to task. Associations were found
      between performance on the WMIC tasks and scales of the Children's Behavioral
      Questionnaire (CBQ) related to the effortful control of behavior. The Peabody
      Picture Vocabulary Test-III (PPVT-III) distinguished between high and low WMIC
      performance. Results of a discriminant function analysis indicated that
      physiology, temperament, and language were able to correctly predict 90% of WMIC
      performance.

PMID- 14704992
TI  - Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition
      memory.
AB  - Brief and transient early-life stimulation via neonatal handling and neonatal
      novelty exposure can lead to differential changes within the right and left
      brains. In rats, these lateralized changes have been demonstrated behaviorally,
      neuroanatomically, and neurophysiologically. Recently, we found that neonatal
      novelty exposure can prolong the duration of social recognition memory from less
      than 2 hr to at least 24 hr among male rats reared in social isolation and that
      this enhancement is associated with an initial right-turn preference in a novel
      testing cage. In contrast to stable forms of asymmetry, such as handedness, we
      show that this turning asymmetry is dynamic-decreasing as the animal adjusts to
      the novel testing environment over a 2-day period. This change in turning
      asymmetry was found only among animals that experienced neonatal novelty exposure
      during the first 3 weeks of their lives. Furthermore, individual differences in
      short-term social recognition memory for a conspecific can be predicted by this
      change in functional asymmetry.

PMID- 14704993
TI  - Molecular definition of predictive indicators of stable protein expression in
      recombinant NS0 myeloma cells.
AB  - We have generated a molecular description of the loci at which
      stability/instability of expression of a monoclonal antibody (MAb) (anti-CD38)
      occurs within the GS-NS0 expression system. Critically, these data show that, in
      the absence of changes to copy number for the recombinant gene sequences, all
      cell lines examined exhibit a progressive loss (instability) in expression of
      mRNA during prolonged culture. However, not all cell lines express instability at
      the level of MAb protein production. The molecular distinction between stable and
      unstable production at the protein level is a reflection of the cellular amount
      of recombinant mRNA encoding MAb. Our data indicate a threshold level, a putative
      saturation point for utilisation of mRNA in translational/secretory events, that
      defines stability or instability of protein production. Above this level of
      recombinant mRNA expression, cell lines are stable, whereas below this level cell
      lines will show instability of protein production. Our studies indicate that
      absolute levels of expression of recombinant mRNA encoding for MAb in the GS-NS0
      expression system offer a potential predictive indicator for the selection of
      stable cell lines for scale-up. These studies identify molecular facets of host
      cell biology of generic interest for gene regulation and expression and define
      techniques and approaches for enhancement of recombinant protein expression and
      process development.

PMID- 14704994
TI  - Efficient production of a bioactive, multiple disulfide-bonded protein using
      modified extracts of Escherichia coli.
AB  - In this report, we demonstrate that a complex mammalian protein containing
      multiple disulfide bonds is successfully expressed in an E.coli-based cell-free
      protein synthesis system. Initially, disulfide-reducing activities in the cell
      extract prevented the formation of disulfide bonds. However, a simple
      pretreatment of the cell extract with iodoacetamide abolished the reducing
      activity. This extract was still active for protein synthesis even under
      oxidizing conditions. The use of a glutathione redox buffer coupled with the DsbC
      disulfide isomerase and pH optimization produced 40 microg/mL of active urokinase
      protease in a simple batch reaction. This result not only demonstrates efficient
      production of complex proteins, it also emphasizes the control and flexibility
      offered by the cell-free approach.

PMID- 14704995
TI  - Optimization of an in vivo plant P450 monooxygenase system in Saccharomyces
      cerevisiae.
AB  - Cytochrome P450s are heme-thiolate oxygenases involved in a wide number of
      reactions such as epoxidation, hydroxylation, and demethylation. Heterologously
      expressed eukaryotic P450s are potentially useful biocatalysts for stereospecific
      oxygenation reactions under mild conditions. Numerous factors, such as
      intracellular pH, cytochrome P450, cytochrome P450 reductase, NADPH, and oxygen
      concentration all influence the in vivo activity. To systematically examine these
      factors, we selected ferulate 5-hydroxylase (F5H), a plant P450, with the
      Saccharomyces cerevisiae WAT11 strain as an expression host. Two media
      compositions and two cultivation procedures were investigated to optimize the in
      vivo activity of F5H. We modified a previously published selective growth medium
      (Pompon et al. [1996] Methods Enzymol 272:51-64) that increased the specific
      growth rate and cell yield of the host strain. A cultivation procedure with
      separate growth and induction stages that each contained selective media resulted
      in a 45% increase of whole cell F5H specific activity. In a medium designed for
      simultaneous growth and induction, we observed a 2.6-fold higher specific F5H
      activity, but substantially lower cell yield. Surprisingly, in this medium the
      higher specific F5H activity did not correlate with a higher P450 concentration.
      The effects of addition of the first committed heme precursor, delta
      aminolevulinic acid, and Fe(III) at the beginning of induction period were also
      studied for our two-stage procedure. A small, but significant (P < 0.05) increase
      in whole cell F5H activity was observed following ALA addition.

PMID- 14704996
TI  - Large-scale expansion of cytomegalovirus-specific cytotoxic T cells in suspension
      culture.
AB  - Clinical trials in recent years involving the adoptive transfer of antigen
      specific cytotoxic T lymphocytes (CTL) have shown promise in restoring immunity
      against viral infection and reducing tumor burden in patients with solid and
      hematological malignancies. However, the large cell number required to achieve
      efficacy, 10(9) to 10(11), makes routine application of adoptive immunotherapy
      impractical. Investigation into new methods of CTL expansion may be useful in
      addressing this problem. Use of stirred suspension bioreactors are one such
      method that may allow large-scale T-cell expansion. Suspension cultures offer
      advantages over conventional static culture methods, including providing a
      homogeneous culture environment, and the potential for optimization and control
      of culture conditions. We generated cytomegalovirus (CMV)-specific CTL and
      investigated the potential of stirred bioreactor systems for expansion of large
      cell numbers. We found that CTL can be readily expanded ( > 200-fold) from
      cryopreserved stocks by nonspecific stimulation in the presence of allogeneic
      feeder cells and interleukin-2 (IL-2). Activated CTL inoculated into either
      suspension or static cultures could be subsequently expanded tenfold, and showed
      similar growth kinetics and metabolism independent of the culture vessel used.
      Furthermore, CTL remained specific for CMVpp65 peptide through the expansion
      phases, as demonstrated by pp65-tetramer staining ( > 95% tetramer(+)) and
      cytotoxicity assays. This study indicates that suspension reactor systems may be
      useful in large-scale expansion of antigen-specific CTL lines or clones, and may
      facilitate the advancement of routine adoptive immunotherapy.

PMID- 14704997
TI  - Identification of various lipolytic enzymes in crude porcine pancreatic lipase
      preparations using covalent fluorescent inhibitors.
AB  - We developed a specific method for determination and discrimination of lipo
      /estero-lytic enzymes in crude lipase preparations. Here we study the composition
      of commercial porcine pancreatic lipase (PPL), since it is widely used for
      bioconversions of synthetic and natural substrates. Our method is based on
      incubation of enzyme samples with fluorescently labeled alkyl- or dialkylglyceryl
      phosphonates in an appropriate solvent followed by protein separation by
      electrophoresis and fluorescence detection with a CCD camera. After incubation
      with short-chain alkylphosphonate solubilized by taurodeoxycholate, crude PPL
      preparations showed a very weak band at 50 kDa, which is indicative of low PPL
      concentrations in these samples. In addition, seven other fluorescent bands were
      detected. The band at the lowest molecular weight corresponded to alpha
      chymotrypsin. Two intensive fluorescent bands were in the molecular weight range
      of chymotrypsinogen (26 kDa) and four weak bands were in the range 20-24 kDa.
      Long-chain dialkylglycerophosphonate labeled two protein bands in crude PPL:
      alpha-chymotrypsin and a very intensive band corresponding to the molecular
      weight of chymotrypsinogen. Detection of cholesterol esterase (98 kDa) in crude
      PPL preparations depended on addition of the protease inhibitor
      phenylmethylsulfonyl fluoride (PMSF) to the incubation mix, as demonstrated by
      spiking with cholesterol esterase. Thus, commercial crude PPL preparations
      contain a variety of estero-/lipo-lytic enzymes in addition to rather low amounts
      of active PPL, which should be considered when using crude PPL for
      bioconversions. Our method can also be used to show whether an isolated
      esterolytic activity corresponds to a single protein or isoenzymes. Here we
      confirm by 2D-electrophoretic separation of "pure" PPL that PPL exists as
      isoenzymes in different glycosylated forms.

PMID- 14704998
TI  - Effect of fermentation broth and biosurfactants on mass transfer during liquid
      liquid extraction.
AB  - Mass transfer rates in liquid-liquid extraction processes can be seriously
      affected by the presence of surface-active contaminants. This is especially true
      of applications of a biotechnological origin, where the microorganism used in the
      process may produce the surface-active contaminants. An investigation into the
      effects of soluble and insoluble fermentation broth components on mass transfer
      using chloramphenicol extraction into octanol as the model system was conducted.
      Soluble components produced during fermentation were found to adsorb to the
      interface, where they reduced the overall mass transfer coefficient by up to 70%.
      After fractionation it was found that components in the weight range from 10-30
      kDa had the greatest effect on mass transfer. Protein and phospholipid compounds
      of similar size were found to reduce the overall mass transfer coefficient to a
      similar extent to the broth components at concentrations around 0.001mg/l. The
      biomass produced during the fermentation also reduced mass transfer
      substantially, and it is likely that this was due to physical blockage of the
      interface.

PMID- 14704999
TI  - Use of protein charge ladders to study electrostatic interactions during protein
      ultrafiltration.
AB  - Recent studies have demonstrated the importance of electrostatic interactions in
      membrane systems, but there is still controversy about the underlying phenomena.
      Protein charge ladders, consisting of a set of chemical derivatives of a given
      protein that differ by single charge groups, were used to quantify the
      electrostatic interactions during protein ultrafiltration. Myoglobin charge
      ladders were generated by acylation, with the different derivatives analyzed
      simultaneously by capillary electrophoresis. Filtration experiments were
      performed using polyethersulfone and composite regenerated cellulose membranes,
      with the membrane charge determined from the streaming potential. As expected,
      the rejection increased as the protein became more heavily charged due to the
      increase in electrostatic repulsion. However, the transmission of the weakly
      charged myoglobin species increased dramatically at very low ionic strength. This
      increase in transmission was attributed to a shift in pH within the pore caused
      by hydrogen ion partitioning into the charged membrane. The sieving data were in
      good agreement with theoretical calculations accounting for the effects of this
      pH shift on the electrostatic interactions.

PMID- 14705000
TI  - Maximizing interferon-gamma production by Chinese hamster ovary cells through
      temperature shift optimization: experimental and modeling.
AB  - The Chinese hamster ovary (CHO) cell line producing interferon-gamma (IFN-gamma)
      exhibits a 2-fold increase in specific productivity when grown at 32 degrees C
      compared to 37 degrees C. Low temperature also causes growth arrest, meaning that
      the cell density is significantly lower at 32 degrees C, nutrients are consumed
      at a slower rate and the batch culture can be run for a longer period of time
      prior to the onset of cell death. At the end of the batch, product concentration
      is doubled at the low temperature. However, the batch time is nearly doubled as
      well, and this causes volumetric productivity to only marginally improve by using
      low temperature. One approach to alleviate the problem of slow growth at low
      temperature is to utilize a biphasic process, wherein cells are cultured at 37
      degrees C for a period of time in order to obtain reasonably high cell density
      and then the temperature is shifted to 32 degrees C to achieve high specific
      productivity. Using this approach, it is hypothesized that IFN-gamma volumetric
      productivity would be maximized. We developed and validated a model for
      predicting the optimal point in time at which to shift the culture temperature
      from 37 degrees C to 32 degrees C. It was found that by shifting the temperature
      after 3 days of growth, the IFN-gamma volumetric productivity is increased by 40%
      compared to growth and production at 32 degrees C and by 90% compared to 37
      degrees C, without any decrease in total production relative to culturing at 32
      degrees C alone. The modeling framework presented here is applicable for
      optimizing controlled proliferation processes in general.

PMID- 14705001
TI  - Recolonization of laser-ablated bacterial biofilm.
AB  - The recolonization of laser-ablated bacterial monoculture biofilm was studied in
      the laboratory by using a flow-cytometer system. The marine biofilm-forming
      bacterium Pseudoalteromonas carrageenovora was used to develop biofilms on
      titanium coupons. Upon exposure to a low-power pulsed irradiation from an Nd:YAG
      laser, the coupons with biofilm were significantly reduced both in terms of total
      viable count (TVC) and area cover. The energy density used for a pulse of 5 ns
      was 0.1 J/cm(2) and the durations of irradiation exposure were 5 and 10 min. When
      placed in a flow of dilute ZoBell marine broth medium (10%) the laser-destructed
      bacterial film in a flow-cytometer showed significant recovery over a period of
      time. The flow of medium was regulated at 3.2 ml/min. The increase in area cover
      and TVC, however, was significantly less than that observed for nonirradiated
      control (t-test, P< 0.05). The coupons were observed for biofilm area cover and
      TVC at different intervals (3, 6, and 9 h) after irradiation. While the biofilm
      in the control coupon at the end of 9 h of exposure showed 95.6 +/- 4.1% cover,
      the 5- and 10-min irradiated samples after 9 h showed 60.3 +/- 6.5 and 37.4 +/-
      12.1% area cover, respectively. The reduced rate of recolonization compared to
      control was thought be due to the lethal and sublethal impacts of laser
      irradiation on bacteria. This observation thus provided data on the online
      recolonization speed of biofilm, which is important when considering pulsed laser
      irradiation as an ablating technique of biofilm formation and removal in natural
      systems.

PMID- 14705002
TI  - Quantitative analysis of membrane fouling by protein mixtures using MALDI-MS.
AB  - Binary aqueous solutions of bovine serum albumin (BSA) and beta-lactoglobulin
      (bLG) were subject to flux-stepping and constant flux ultrafiltration to identify
      the apparent critical flux and to study the mechanisms and factors affecting
      fouling when the membrane is permeable to one protein component. Membranes from
      these filtration experiments were analyzed using matrix-assisted laser desorption
      ionization mass spectrometry (MALDI-MS) to locate and quantify levels of fouling
      below and above the apparent critical flux. Hydrophilic (PLTK) regenerated
      cellulose and hydrophobic (PBTK) polysulfone asymmetric membranes were used, both
      of 30 kDa nominal molecular weight cut-off. For the hydrophilic PLTK membrane,
      protein deposition was shown to depend on electrostatic forces, exhibiting little
      or no fouling when the proteins had the same charge sign as that of the membrane.
      This was found to apply for both dilute equal mass-per-unit-volume and equimolar
      binary mixtures. For the PBTK membrane, hydrophobic protein-membrane attractive
      forces were sufficiently strong to cause deposition of bLG even in the presence
      of repulsive electrostatic forces. For the PBTK membrane deposition exceeded
      monolayer coverage below and above apparent critical flux conditions but for the
      PLTK membrane this generally occurred when the apparent critical flux was
      exceeded. MALDI-MS was shown to be a facile direct analytical technique for
      individually quantifying adsorbed proteins on membrane surfaces at levels as low
      as 50 fmol/mm(2). The high levels of compound specificity inherent to mass
      spectrometry make this approach especially suited to the quantification of
      individual components in mixed deposits. In this study, MALDI-MS was found to be
      successful in identifying and quantifying the protein species responsible for
      fouling.

PMID- 14705003
TI  - Strategies for the cryopreservation of microencapsulated cells.
AB  - The major challenge in developing cryopreservation protocols for
      microencapsulated cells is that the relatively large size (300-400 microm) and
      the fragile semipermeable membrane of microcapsules makes them particularly prone
      to cryodamage. Rapid-cooling cryopreservation protocols with high DMSO
      concentrations (3.5M, 25% v/v) resulted in low post-thaw cell viability (<10%),
      which did not improve with higher concentrations (4.5M, 32% v/v) and longer
      exposure to DMSO, even though the majority of microcapsules (60-80%) remained
      intact. Subsequent investigations of slow cooling with a range of DMSO and EG
      concentrations resulted in a much higher post-thaw cell viability (80-85%), with
      the majority of the microcapsules remaining intact ( approximately 60%) when DMSO
      was used at a concentration of 2.8M (20% v/v) and EG at a concentration of 2.7M
      (15% v/v). The presence of 0.25M sucrose significantly improved post-thaw cell
      viability upon slow cooling with 2.8M (20% v/v) DMSO, although it had no effect
      on microcapsule integrity. Multistep exposure and removal of sucrose did not
      significantly improve either post-thaw cell viability or microcapsule integrity,
      compared to a single-step protocol. Ficoll 20% (w/v) also did not significantly
      improve post-thaw cell viability and microcapsule integrity. Hence, the optimal
      condition for microcapsule cryopreservation developed in this study is slow
      cooling with 2.8M (20% v/v) DMSO and 0.25M sucrose.

PMID- 14705004
TI  - Functional display of foreign protein on surface of Escherichia coli using N
      terminal domain of ice nucleation protein.
AB  - We investigated the ability of the N-terminal domain of InaK, an ice nucleation
      protein from Pseudomonas syringae KCTC1832, to act as an anchoring motif for the
      display of foreign proteins on the Escherichia coli cell surface. Total
      expression level and surface display efficiency of green fluorescent protein
      (GFP) was compared following their fusion with either the N-terminal domain of
      InaK (InaK-N), or with the known truncated InaK containing both N- and C-terminal
      domains (InaK-NC). We report that the InaK-N/GFP fusion protein showed a similar
      cell surface display efficiency ( approximately 50%) as InaK-NC/GFP,
      demonstrating that the InaK N-terminal region alone can direct translocation of
      foreign proteins to the cell surface and can be employed as a potential cell
      surface display motif. Moreover, InaK-N/GFP showed the highest levels of total
      expression and surface display based on unit cell density. InaK-N was also
      successful in directing cell surface display of organophosphorus hydrolase (OPH),
      confirming its ability to act as a display motif.

PMID- 14705005
TI  - Enhancement of apparent substrate selectivity of proteinase K encapsulated in
      liposomes through a cholate-induced alteration of the bilayer permeability.
AB  - Proteinase K-containing liposomes with highly selective membrane permeability
      properties were prepared. The selectivity obtained was with respect to the two
      substrate molecules added to the external aqueous phase of the liposomes: acetyl
      L-Ala-Ala-Ala-p-nitroanilide (Ac-AAA-pNA) and succinyl-L-Ala-Ala-Ala-p
      nitroanilide (Suc-AAA-pNA). The liposome-forming lipid used was POPC (1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine) and modulation of the membrane permeability
      was achieved using the detergent cholate. Proteinase K-containing mixed liposomes
      (PKCL) were prepared by adding cholate to preformed proteinase K-containing POPC
      liposomes (PKL) at a defined effective cholate/POPC molar ratio in the liposomal
      bilayer membrane R(e). Proteinase K was kept inside PKCL with a negligible amount
      of leakage into the bulk aqueous phase at R(e) < or = 0.30. At higher R(e),
      leakage of proteinase K was pronounced, even under conditions where POPC/cholate
      mixed liposomes seemed to be still intact (0.30 < R(e) < or = 0.39). At R(e) < or
      = 0.30, the reactivity of proteinase K in the PKCL measured with the externally
      added substrate Ac-AAA-pNA increased with increasing R(e), while the reactivity
      measured with Suc-AAA-pNA remained low, regardless of the R(e) value. This showed
      that externally added Ac-AAA-pNA molecules permeated the liposomal membrane more
      easily than Suc-AAA-pNA by modulating the membrane with cholate. Consequently, Ac
      AAA-pNA was hydrolyzed in PKCL with considerably higher apparent substrate
      selectivity in comparison with the cases of proteinase K in PKL and free
      proteinase K (without liposomal encapsulation). The results obtained clearly
      demonstrate that the prepared PKCL can be utilized as a kind of nano-scaled
      bioreactor system which can take up a particular target substrate with high
      apparent substrate selectively from the external phase of the liposomes. Inside
      the liposomes, the target substrate is then converted into the corresponding
      products.

PMID- 14705006
TI  - Preparation of nanoparticles by electrocoagulation from soluble exopolysaccharide
      produced by Claviceps viridis.
AB  - Electrocoagulation is an evolving technology that has been effectively applied
      for wastewater treatment but its applications in biotechnology and nanotechnology
      are very limited. This method was applied for the preparation of nanoparticles
      from soluble exopolysaccharide (EPS) produced by Claviceps viridis in a submerged
      batch culture. A cathode/anode pair electrode (Al or Fe) system was used for
      determination of the separation rates of electrocoagulation and the yields of EPS
      nanoparticles production. The separation rates of 0.170 +/- 0.003 mg EPS/sec (Fe
      electrodes) and 0.250 +/- 0.003 mg EPS/sec (Al electrodes) were calculated for
      voltage gradient 1 V/1 cm of electrodes distance and were constant during
      experiments. The specific yield of EPS nanoparticles production based on the
      consumed electric power was dependent on the material of the electrodes and its
      value was determined as 0.71 +/- 0.01 mg EPS/W for Fe electrodes and 0.91 +/-
      0.01 mg EPS/W for Al electrodes, respectively.

PMID- 14705007
TI  - Fundamental Escherichia coli biochemical pathways for biomass and energy
      production: identification of reactions.
AB  - Cells grow by oxidizing nutrients using a complex network of biochemical
      reactions. During this process new biological material is produced along with
      energy used for maintaining cellular organization. Because the metabolic network
      is highly branched, these tasks can be accomplished using a wide variety of
      unique reaction sequences. However, evolutionary pressures under carbon-limited
      growth conditions likely select organisms that utilize highly efficient pathways.
      Using elementary-mode analysis, we demonstrate that the metabolism of the
      bacterium Escherichia coli contains four unique pathways that most efficiently
      convert glucose and oxygen into new cells and maintenance energy under any level
      of oxygen limitation. Observed regulatory patterns and experimental findings
      suggest growing cells use these highly efficient pathways. It is predicted that
      five knockout mutations generate a strain that supports growth using only the
      most efficient reaction sequence. The analysis approach should be generally
      useful for predicting metabolic capabilities and efficient network designs based
      on only genomic information.

PMID- 14705008
TI  - Blocking caspase-3 activity with a U6 SnRNA promoter-driven ribozyme enhances
      survivability of CHO cells cultured in low serum medium and production of
      interferon-beta.
AB  - Apoptosis responding to various insults in bioreactors was observed to reduce
      cell viability and prevent cells from growing to high density. Inhibition of
      apoptosis in different ways has proved to be effective in keeping cells viable in
      high density and result in higher recombinant protein production. In apoptosis,
      death signals activate a family of proteinases, namely caspases, in a cascade and
      ultimately activate the final effector proteinase, caspase-3, which cleaves
      various substrates and drives the cells irreversibly to death. Caspase-3 is the
      executioner of an apoptotic cell and thus plays a central role in apoptosis.
      Therefore inhibition of caspase-3 may provide an effective way for apoptosis
      prevention. In this study, we designed a ribozyme targeted at the 451 nt of
      hamster caspase-3's open reading frame (ORF) and the ribozyme was proved to be
      effective in cleaving caspase-3 mRNA in vitro. Then, the ribozyme was cloned into
      a vector under the control of U6 snRNA promoter, an RNA polymerase III promoter,
      for high rate of transcription in vivo. The vector was transfected into an
      interferon-beta producing recombinant CHO cell line, and some clones were
      screened out that exhibited low caspase-3 production by Western blot analysis.
      One such clone was then further analyzed and it showed good anti-apoptosis
      property with respect to cell viability, cell density, and interferon-beta
      production.

PMID- 14705009
TI  - Construction of high-density bacterial colony arrays and patterns by the ink-jet
      method.
AB  - We have developed a method for fabricating bacterial colony arrays and complex
      patterns using commercially available ink-jet printers. Bacterial colony arrays
      with a density of 100 colonies/cm(2) were obtained by directly ejecting
      Escherichia coli (E. coli) onto agar-coated substrates at a rapid arraying speed
      of 880 spots per second. Adjusting the concentration of bacterial suspensions
      allowed single colonies of viable bacteria to be obtained. In addition, complex
      patterns of viable bacteria as well as bacteria density gradients were
      constructed using desktop printers controlled by a simple software program.

PMID- 14705010
TI  - Fluid mechanics of a spinner-flask bioreactor.
AB  - Spinner-flask bioreactors have been used for the production of articular
      cartilage in vitro. The dynamic environment within bioreactors is known to
      significantly affect the growth and development of the tissue. The present
      research focuses on the experimental and numerical characterization of the flow
      field within a spinner flask operating under conditions used to produce
      cartilage. Laboratory experiments carried out in a scaled-up model bioreactor
      employ particle-image velocimetry (PIV) to determine velocity and shear-rate
      fields in the vicinity of the construct closest to the stir bar, in addition to
      turbulence properties. Numerical computations calculated using FLUENT, a
      commercial software package, simulate the flow field in the same model bioreactor
      under similar operating conditions. In the computations, scaffolds were modeled
      as both solid and porous media with different permeabilities and flow rates
      through various faces of the construct nearest the stir bar were examined.

PMID- 14705011
TI  - Reconsidering the use of photosynthetic bacteria for removal of sulfide from
      wastewater.
AB  - The feasibility of using photosynthetic sulfide-oxidizing bacteria to remove
      sulfide from wastewater in circumstances where axenic cultures are unrealistic
      has been completely reconsidered on the basis of known ecophysiological data, and
      the principles of photobioreactor and chemical reactor engineering. This has
      given rise to the development of two similar treatment concepts relying on
      biofilms dominated by green sulfur bacteria (GSB) that develop on the exterior of
      transparent surfaces suspended in the wastewater. The GSB are sustained and
      selected for by radiant energy in the band 720-780 nm, supplied from within the
      transparent surface. A model of one of these concepts was constructed and with it
      the reactor concept was proven. The dependence of sulfide-removal rate on bulk
      sulfide concentration has been ascertained. The maximum net areal sulfide removal
      rate was 2.23 g m-(2) day-(1) at a bulk sulfide concentration of 16.5 mg L(-1)
      and an incident irradiance of 1.51 W m(-2). The system has a demonstrated
      capacity to mitigate surges in sulfide load, and appears to use much less radiant
      power than comparable systems. The efficacy with which this energy was used for
      sulfide removal was 1.47 g day(-1) W(-1). The biofilm was dominated by GSB, and
      evidence gathered indicated that other types of phototrophs were not present.

PMID- 14705012
TI  - Enhanced biological phosphorus removal in a sequencing batch reactor using
      propionate as the sole carbon source.
AB  - An enhanced biological phosphorus removal (EBPR) system was developed in a
      sequencing batch reactor (SBR) using propionate as the sole carbon source. The
      microbial community was followed using fluorescence in situ hybridization (FISH)
      techniques and Candidatus 'Accumulibacter phosphatis' were quantified from the
      start up of the reactor until steady state. A series of SBR cycle studies was
      performed when 55% of the SBR biomass was Accumulibacter, a confirmed
      polyphosphate accumulating organism (PAO) and when Candidatus 'Competibacter
      phosphatis', a confirmed glycogen-accumulating organism (GAO), was essentially
      undetectable. These experiments evaluated two different carbon sources
      (propionate and acetate), and in every case, two different P-release rates were
      detected. The highest rate took place while there was volatile fatty acid (VFA)
      in the mixed liquor, and after the VFA was depleted a second P-release rate was
      observed. This second rate was very similar to the one detected in experiments
      performed without added VFA.A kinetic and stoichiometric model developed as a
      modification of Activated Sludge Model 2 (ASM2) including glycogen economy, was
      fitted to the experimental profiles. The validation and calibration of this model
      was carried out with the cycle study experiments performed using both VFAs. The
      effect of pH from 6.5 to 8.0 on anaerobic P-release and VFA-uptake and aerobic P
      uptake was also studied using propionate. The optimal overall working pH was
      around 7.5. This is the first study of the microbial community involved in EBPR
      developed with propionate as a sole carbon source along with detailed process
      performance investigations of the propionate-utilizing PAOs.

PMID- 14705013
TI  - Toluene removal from waste air using a flat composite membrane bioreactor.
AB  - In this report, gaseous toluene biodegradation results in a flat composite
      membrane reactor inoculated with Pseudomonas putida TVA8 are presented.
      Preliminary abiotic experiments showed that transport of toluene through the
      membrane was linearly and negatively correlated with the gas residence time
      (tau). During a 339-day biofiltration experiment, the influence of gas residence
      time (2-24 sec) and mass loading rate (B(v); 10-483 g x m(-3) h(-1)) on the
      toluene elimination capacity was investigated. A maximum elimination capacity
      (EC(max)) of 397 g x m(-3) h(-1) was achieved at tau = 24 sec and B(v) = 473 g x
      m(-3) h(-1). Expressed per unit membrane area, the EC(m,max) was 0.793 g x m(-2)
      h(-1), which is five times higher than results obtained with other membrane
      bioreactor experiments in the same range of loading rates. At low gas residence
      times, reactor performance was limited by mass transfer. Toluene concentration
      profiles along the membrane were measured for several biotic and abiotic
      conditions. For inlet concentrations (C(in)) up to 1 g x m(-3), more than 90% was
      eliminated at 15 cm from the reactor inlet. For C(in) > 1.65 g x m(-3), longer
      membranes are necessary to obtain these high removal efficiencies.

PMID- 14705014
TI  - Overcoming shear stress of microalgae cultures in sparged photobioreactors.
AB  - In the present work we identified and quantified the effect of hydrodynamic
      stress on two different microalgae strains, Dunaliella tertiolecta and D. salina,
      cultivated in bench-scale bubble columns. The cell death rate constant increased
      with increasing gas-entrance velocity at the sparger. Dunaliella salina was
      slightly more sensitive than D. tertiolecta. The critical gas-entrance velocities
      were approximately 50 and 30 m s(-1) for D. tertiolecta and D. salina,
      respectively. The effects of gas-flow rate, culture height, and nozzle diameter
      on the death rate constant were also studied. From these results it was concluded
      that bubble rising and bubble bursting are not responsible for cell death.
      Regarding nozzle diameter, small nozzles were more detrimental to cells. The
      bubble formation at the sparger was found to be the main event leading to cell
      death.

PMID- 14705015
TI  - Analysis of size distribution and areal cell density of ammonia-oxidizing
      bacterial microcolonies in relation to substrate microprofiles in biofilms.
AB  - A fine-scale in situ spatial organization of ammonia-oxidizing bacteria (AOB) in
      biofilms was investigated by combining molecular techniques (i.e., fluorescence
      in situ hybridization (FISH) and 16S rDNA-cloning analysis) and microelectrode
      measurements. Important parameters of AOB microcolonies such as size distribution
      and areal cell density of the microcolonies were determined and correlated with
      substrate microprofiles in the biofilms. In situ hybridization with a nested 16S
      rRNA-targeted oligonucleotide probe set revealed two different populations of
      AOB, Nitrosomonas europaea-lineage and Nitrosospira multiformis-lineage,
      coexisting in an autotrophic nitrifying biofilm. Nitrosospira formed looser
      microcolonies, with an areal cell density of 0.51 cells microm(-2), which was
      half of the cell density of Nitrosomonas (1.12 cells microm(-2)). It is
      speculated that the formation of looser microcolonies facilitates substrate
      diffusion into the microcolonies, which might be a survival strategy to low O(2)
      and NH(4) (+) conditions in the biofilm. A long-term experiment (4-week
      cultivation at different substrate C/N ratios) revealed that the size
      distribution of AOB microcolonies was strongly affected by better substrate
      supply due to shorter distance from the surface and the presence of organic
      carbon. The microcolony size was relatively constant throughout the autotrophic
      nitrifying biofilm, while the size increased by approximately 80% toward the
      depth of the biofilm cultured at the substrate C/N = 1. A short-term (
      approximately 3 h) organic carbon addition experiment showed that the addition of
      organic carbon created interspecies competition for O(2) between AOB and
      heterotrophic bacteria, which dramatically decreased the in situ NH(4) (+)-uptake
      activity of AOB in the surface of the biofilms. This result might explain the
      spatial distribution of AOB microcolony size in the biofilms cultured at the
      substrate C/N = 1. These experimental results suggest O(2) and organic carbon
      were the main factors controlling the spatial organization and activity of AOB in
      biofilms. These findings are significantly important to further improve
      mathematical models used to describe how the slow-growing AOB develop their
      niches in biofilms and how that configuration affects nitrification performance
      in the biofilm.

PMID- 14705016
TI  - Cephalosporin C production by immobilized Cephalosporium acremonium cells in a
      repeated batch tower bioreactor.
AB  - The industrial production of antibiotics with filamentous fungi is usually
      carried out in conventional aerated and agitated tank fermentors. Highly viscous
      non-Newtonian broths are produced and a compromise must be found between
      convenient shear stress and adequate oxygen transfer. In this work, cephalosporin
      C production by bioparticles of immobilized cells of Cephalosporium acremonium
      ATCC 48272 was studied in a repeated batch tower bioreactor as an alternative to
      the conventional process. Also, gas-liquid oxygen transfer volumetric
      coefficients, k(L)a, were determined at various air flow-rates and alumina
      contents in the bioparticle. The bioparticles were composed of calcium alginate
      (2.0% w/w), alumina ( < 44 micra), cells, and water. A model describing the cell
      growth, cephalosporin C production, oxygen, glucose, and sucrose consumption was
      proposed. To describe the radial variation of oxygen concentration within the
      pellet, the reaction-diffusion model forecasting a dead core bioparticle was
      adopted. The k(L)a measurements with gel beads prepared with 0.0, 1.0, 1.5, and
      2.0% alumina showed that a higher k(L)a value is attained with 1.5 and 2.0%. An
      expression relating this coefficient to particle density, liquid density, and air
      velocity was obtained and further utilized in the simulation of the proposed
      model. Batch, followed by repeated batch experiments, were accomplished by
      draining the spent medium, washing with saline solution, and pouring fresh medium
      into the bioreactor. Results showed that glucose is consumed very quickly, within
      24 h, followed by sucrose consumption and cephalosporin C production. Higher
      productivities were attained during the second batch, as cell concentration was
      already high, resulting in rapid glucose consumption and an early derepression of
      cephalosporin C synthesizing enzymes. The model incorporated this improvement
      predicting higher cephalosporin C productivity.

PMID- 14705017
TI  - Combined in-fermenter extraction and cross-flow microfiltration for improved
      inclusion body processing.
AB  - In this study we demonstrate a new in-fermenter chemical extraction procedure
      that degrades the cell wall of Escherichia coli and releases inclusion bodies
      (IBs) into the fermentation medium. We then prove that cross-flow microfiltration
      can be used to remove 91% of soluble contaminants from the released IBs. The
      extraction protocol, based on a combination of Triton X-100, EDTA, and
      intracellular T7 lysozyme, effectively released most of the intracellular soluble
      content without solubilising the IBs. Cross-flow microfiltration using a 0.2
      microm ceramic membrane successfully recovered the granulocyte macrophage-colony
      stimulating factor (GM-CSF) IBs with removal of 91% of the soluble contaminants
      and virtually no loss of IBs to the permeate. The filtration efficiency, in terms
      of both flux and transmission, was significantly enhanced by in-fermenter
      Benzonase digestion of nucleic acids following chemical extraction. Both the
      extraction and filtration methods exerted their efficacy directly on a crude
      fermentation broth, eliminating the need for cell recovery and resuspension in
      buffer. The processes demonstrated here can all be performed using just a
      fermenter and a single cross-flow filtration unit, demonstrating a high level of
      process intensification. Furthermore, there is considerable scope to also use the
      microfiltration system to subsequently solubilise the IBs, to separate the
      denatured protein from cell debris, and to refold the protein using
      diafiltration. In this way refolded protein can potentially be obtained, in a
      relatively pure state, using only two unit operations.

PMID- 14705018
TI  - First principles computational study of the active site of arginase.
AB  - Ab initio density functional theory (DFT) methods were used to investigate the
      structural features of the active site of the binuclear enzyme rat liver
      arginase. Special emphasis was placed on the crucial role of the second shell
      ligand interactions. These interactions were systematically studied by performing
      calculations on models of varying size. It was determined that a water molecule,
      and not hydroxide, is the bridging exogenous ligand. The carboxylate ligands
      facilitate the close approach of the Mn (II) ions by attenuating the metal-metal
      electrostatic repulsion. Of the two metals, Mn(A) was shown to carry a larger
      positive charge. Analysis of the electronic properties of the active site
      revealed that orbitals involving the terminal Asp234 residue, as well as the
      flexible micro-1,1 bridging Asp232, lie at high energies, suggesting weaker
      coordination. This is reflected in certain structural variability present in our
      models and is also consistent with recent experimental findings. Finally,
      implications of our findings for the biological function of the enzyme are
      delineated.

PMID- 14705019
TI  - Sequence-based study of two related proteins with different folding behaviors.
AB  - Z(SPA-1) is an engineered protein that binds to its parent, the three-helix
      bundle Z domain of staphylococcal protein A. Uncomplexed Z(SPA-1) shows a reduced
      helix content and a melting behavior that is less cooperative, compared with the
      wild-type Z domain. Here we show that the difference in folding behavior between
      these two sequences can be partly understood in terms of an off-lattice model
      with 5-6 atoms per amino acid and a minimalistic potential, in which folding is
      driven by backbone hydrogen bonding and effective hydrophobic attraction.

PMID- 14705020
TI  - Lipoxygenase interactions with natural flavonoid, quercetin, reveal a complex
      with protocatechuic acid in its X-ray structure at 2.1 A resolution.
AB  - PUFA metabolites have a profound effect on inflammatory diseases and cancer
      progression. Blocking their production by inhibiting PUFA metabolizing enzymes
      (dioxygenases: cyclooxygenases and LOXs) might be a successful way to control and
      relieve such problems, if we learn to better understand their actions at a
      molecular level. Compounds with strong antioxidative and free radical scavenging
      properties, such as polyphenols, could be effective in blocking PUFA activities,
      and natural flavonoids possess such qualities. Quercetin belongs to the group of
      natural catecholic compounds and is known as a potent, competitive inhibitor of
      LOX. Structural analysis reveals that quercetin entrapped within LOX undergoes
      degradation, and the resulting compound has been identified by X-ray analysis as
      protocatechuic acid (3,4-dihydroxybenzoic acid) positioned near the iron site.
      Its C3-OH group points toward His523, C4-OH forms a hydrogen bond with O=C from
      the enzyme's C-terminus, and the carboxylic group is incorporated into the
      hydrogen bonding network of the active-site neighborhood via Gln514. This
      unexpected result, together with our previous observations concerning other
      polyphenols, yields new evidence about the metabolism of natural flavonoids.
      These compounds might be vulnerable to the co-oxidase activity of LOX, leading to
      enzyme-stimulated oxidative degradation, which results in an inhibitor of a lower
      molecular weight.

PMID- 14705021
TI  - Proteomic signatures: amino acid and oligopeptide compositions differentiate
      among phyla.
AB  - Availability of complete genome sequences allows in-depth comparison of single
      residue and oligopeptide compositions of the corresponding proteomes. We have
      used principal component analysis (PCA) to study the landscape of compositional
      motifs across more than 70 genera from all three superkingdoms. Unexpectedly, the
      first two principal components clearly differentiate archaea, eubacteria, and
      eukaryota from each other. In particular, we contrast compositional patterns
      typical of the three superkingdoms and characterize differences between species
      and phyla, as well as among patterns shared by all compositional proteomic
      signatures. These species-specific patterns may even extend to subsets of the
      entire proteome, such as proteins pertaining to individual yeast chromosomes. We
      identify factors that affect compositional signatures, such as living habitat,
      and detect strong eukaryotic preference for homopeptides and palindromic
      tripeptides. We further detect oligopeptides that are either universally over- or
      underabundant across the whole proteomic landscape, as well as oligopeptides
      whose over- or underabundance is phylum- or species-specific. Finally, we report
      that species composition signatures preserve evolutionary memory, providing a new
      method to compare phylogenetic relationships among species that avoids problems
      of sequence alignment and ortholog detection.

PMID- 14705022
TI  - Enriching the sequence substitution matrix by structural information.
AB  - A fundamental step in homology modeling is the comparison of two protein
      sequences: a probe sequence with an unknown structure and function and a template
      sequence for which the structure and function are known. The detection of protein
      similarities relies on a substitution matrix that scores the proximity of the
      aligned amino acids. Sequence-to-sequence alignments use symmetric substitution
      matrices, whereas the threading protocols use asymmetric matrices, testing the
      fitness of the probe sequence into the structure of the template protein. We
      propose a linear combination of threading and sequence-alignment scoring
      function, to produce a single (mixed) scoring table. By fitting a single
      parameter (which is the relative contribution of the BLOSUM 50 matrix and the
      threading energy table of THOM2) we obtain a significant increase in prediction
      capacity in the twilight zone of homology modeling (detecting sequences with <25%
      sequence identity and with very similar structures). For a difficult test of 176
      homologous pairs, with no signal of sequence similarity, the mixed model makes it
      possible to detect between 40 and 100% more protein pairs than the number of
      pairs that are detected by pure threading. Surprisingly, the linear combination
      of the two models is performing better than threading and than sequence alignment
      when the percentage of sequence identity is low. We finally suggest that further
      enrichment of substitution matrices, combing more structural descriptors such as
      exposed surface area, or secondary structure is expected to enhance the signal as
      well.

PMID- 14705023
TI  - Detection of functional modules from protein interaction networks.
AB  - Complex cellular processes are modular and are accomplished by the concerted
      action of functional modules (Ravasz et al., Science 2002;297:1551-1555; Hartwell
      et al., Nature 1999;402:C47-52). These modules encompass groups of genes or
      proteins involved in common elementary biological functions. One important and
      largely unsolved goal of functional genomics is the identification of functional
      modules from genomewide information, such as transcription profiles or protein
      interactions. To cope with the ever-increasing volume and complexity of protein
      interaction data (Bader et al., Nucleic Acids Res 2001;29:242-245; Xenarios et
      al., Nucleic Acids Res 2002;30:303-305), new automated approaches for pattern
      discovery in these densely connected interaction networks are required (Ravasz et
      al., Science 2002;297:1551-1555; Bader and Hogue, Nat Biotechnol 2002;20:991-997;
      Snel et al., Proc Natl Acad Sci USA 2002;99:5890-5895). In this study, we
      successfully isolate 1046 functional modules from the known protein interaction
      network of Saccharomyces cerevisiae involving 8046 individual pair-wise
      interactions by using an entirely automated and unsupervised graph clustering
      algorithm. This systems biology approach is able to detect many well-known
      protein complexes or biological processes, without reference to any additional
      information. We use an extensive statistical validation procedure to establish
      the biological significance of the detected modules and explore this complex,
      hierarchical network of modular interactions from which pathways can be inferred.

PMID- 14705024
TI  - Docking studies and model development of tea polyphenol proteasome inhibitors:
      applications to rational drug design.
AB  - Previously, we demonstrated that natural and synthetic ester bond-containing
      green tea polyphenols were potent and specific non-peptide proteasome inhibitors.
      However, the molecular mechanism of inhibition is currently unknown. Here, we
      report that inhibition of the chymotrypsin activity of the 20S proteasome by (-)
      epigallocatechin-3-gallate (EGCG) is time-dependent and irreversible, implicating
      acylation of the beta5-subunit's catalytic N-terminal threonine (Thr 1). This
      knowledge is used, along with in silico docking experiments, to aid in the
      understanding of binding and inhibition. On the basis of these docking
      experiments, we propose that (-)-EGCG binds the chymotrypsin site in an
      orientation and conformation that is suitable for a nucleophilic attack by Thr 1.
      Consistently, the distance from the electrophilic carbonyl carbon of (-)-EGCG to
      the hydroxyl group of Thr 1 was measured as 3.18 A. Furthermore, the A ring of (
      )-EGCG acts as a tyrosine mimic, binding to the hydrophobic S1 pocket of the
      beta5-subunit. In the process, the (-)-EGCG scissile bond may become strained,
      which could lower the activation energy for attack by the hydroxyl group of Thr
      1. This model is validated by comparison of predicted and actual activities of
      several EGCG analogs, either naturally occurring, previously synthesized, or
      rationally synthesized.

PMID- 14705025
TI  - Gaps in structurally similar proteins: towards improvement of multiple sequence
      alignment.
AB  - An algorithm was developed to locally optimize gaps from the FSSP database. Over
      2 million gaps were identified from all versus all FSSP structure comparisons,
      and datasets of non-identical gaps and flanking regions comprising between 90,000
      and 135,000 sequence fragments were extracted for statistical analysis. Relative
      to background frequencies, gaps were enriched in residue types with small side
      chains and high turn propensity (D, G, N, P, S), and were depleted in residue
      types with hydrophobic side chains (C, F, I, L, V, W, Y). In contrast, regions
      flanking a gap exhibited opposite trends in amino acid frequencies, i.e.,
      enrichment in hydrophobic residues and a high degree of secondary structure. Log
      odds scores of residue type as a function of position in or around a gap were
      derived from the statistics. Three simple experiments demonstrated that these
      scores contained significant predictive information. First, regions where gaps
      were observed in single sequences taken from HOMSTRAD structure-based multiple
      sequence alignments generally scored higher than regions where gaps were not
      observed. Second, given the correct pairwise-aligned cores, the actual positions
      of gaps could be reproduced from sequence more accurately using the structurally
      derived statistics than by using random pairwise alignments. Finally, revision of
      the Clustal-W residue-specific gap opening parameters with this new information
      improved the agreement of Clustal-W alignments with the structure-based
      alignments. At least three applications for these results are envisioned:
      improvement of gap penalties in pairwise (or multiple) sequence alignment,
      prediction of regions of single sequences likely (or unlikely) to contain indels,
      and more accurate placement of gaps in automated pairwise structure alignment.

PMID- 14705026
TI  - Optimizing physical energy functions for protein folding.
AB  - We optimize a physical energy function for proteins with the use of the available
      structural database and perform three benchmark tests of the performance: (1)
      recognition of native structures in the background of predefined decoy sets of
      Levitt, (2) de novo structure prediction using fragment assembly sampling, and
      (3) molecular dynamics simulations. The energy parameter optimization is based on
      the energy landscape theory and uses a Monte Carlo search to find a set of
      parameters that seeks the largest ratio deltaE(s)/DeltaE for all proteins in a
      training set simultaneously. Here, deltaE(s) is the stability gap between the
      native and the average in the denatured states and DeltaE is the energy
      fluctuation among these states. Some of the energy parameters optimized are found
      to show significant correlation with experimentally observed quantities: (1) In
      the recognition test, the optimized function assigns the lowest energy to either
      the native or a near-native structure among many decoy structures for all the
      proteins studied. (2) Structure prediction with the fragment assembly sampling
      gives structure models with root mean square deviation less than 6 A in one of
      the top five cluster centers for five of six proteins studied. (3) Structure
      prediction using molecular dynamics simulation gives poorer performance, implying
      the importance of having a more precise description of local structures. The
      physical energy function solely inferred from a structural database neither
      utilizes sequence information from the family of the target nor the outcome of
      the secondary structure prediction but can produce the correct native fold for
      many small proteins.

PMID- 14705027
TI  - Loss of translational entropy in molecular associations.
AB  - Molecular associations in solution are opposed by the loss of entropy (DeltaS)
      that results from the restriction of motion of each component in the complex.
      Theoretical estimates of DeltaS are essential for rationalizing binding
      affinities, as well as for calculating entropic contribution to enzyme catalysis.
      Recently a statistical-mechanical framework has been proposed for estimating
      efficiently the translational entropy loss (DeltaS(trsl)), while taking
      explicitly into account the complex intermolecular interactions between the
      solute and the solvent. This framework relates the translational entropy of a
      solute in solution to its "free volume," defined as the volume accessible to the
      center of mass of the solute in the presence of the solvent and calculated by
      using an extension of the cell model (CM) for condensed phases. The translational
      entropy of pure water, estimated with the CM algorithm, shows good agreement with
      the experimental information. The free volume of various solutes in water,
      calculated within the CM by using molecular dynamics simulations with explicit
      solvent, displays a strong correlation with the solutes' polar and total surface
      areas. This correlation is used to propose a parameterization that can be used to
      calculate routinely the translational entropy of a solute in water. We also
      applied the CM formalism to calculate the free volume and translational entropy
      loss (DeltaS(trsl)) on binding of benzene to a cavity in a mutant T4-lysozyme.
      Our results agree with previously published estimates of the binding of benzene
      to this mutant T4-lysozyme. These and other considerations suggest that the cell
      model is a simple yet efficient theoretical framework to evaluate the
      translational entropy loss on molecular association in solution.

PMID- 14705028
TI  - Molecular dynamics simulations of peptides containing an unnatural amino acid:
      dimerization, folding, and protein binding.
AB  - We have performed molecular dynamics (MD) simulations to study the dimerization,
      folding, and binding to a protein of peptides containing an unnatural amino acid.
      NMR studies have shown that the substitution of one residue in a tripeptide beta
      strand by the unnatural amino acid Hao (5-HO2CCONH-2-MeO-C6H3-CO-NHNH2) modifies
      the conformational flexibility of the beta-strand and the hydrogen-bonding
      properties of its two edges: The number of hydrogen-bond donors and acceptors
      increases at one edge, whereas at the other, they are sterically hindered. In
      simulations in chloroform, the Hao-containing peptide 9 (i-PrCO-Phe-Hao-Val-NHBu)
      forms a beta-sheet-like hydrogen-bonded dimer, in good agreement with the
      available experimental data. Addition of methanol to the solution induces
      instability of this beta-sheet, as confirmed by the experiments. MD simulations
      also reproduce the folding of the synthetic peptide 1a (i-PrCO-Hao-Ut-Phe-Ile-Leu
      NHMe) into a beta-hairpin-like structure in chloroform. Finally, the Hao
      containing peptide, Ac-Ala-Hao-Ala-NHMe, is shown to form a stable complex with
      the Ras analogue, Rap1 A, in water at room temperature. Together with the
      available experimental data, these simulation studies indicate that Hao
      containing peptides may serve as inhibitors of beta-sheet interactions between
      proteins.

PMID- 14705029
TI  - Improved thermostability of bacillus circulans cyclodextrin glycosyltransferase
      by the introduction of a salt bridge.
AB  - Cyclodextrin glycosyltransferase (CGTase) catalyzes the formation of
      cyclodextrins from starch. Among the CGTases with known three-dimensional
      structure, Thermoanaerobacterium thermosulfurigenes CGTase has the highest
      thermostability. By replacing amino acid residues in the B-domain of Bacillus
      circulans CGTase with those from T. thermosulfurigenes CGTase, we identified a B.
      circulans CGTase mutant (with N188D and K192R mutations), with a strongly
      increased activity half-life at 60 degrees C. Asp188 and Arg192 form a salt
      bridge in T. thermosulfurigenes CGTase. Structural analysis of the B. circulans
      CGTase mutant revealed that this salt bridge is also formed in the mutant. Thus,
      the activity half-life of this enzyme can be enhanced by rational protein
      engineering.

PMID- 14705030
TI  - Molecular basis for redox-Bohr and cooperative effects in cytochrome c3 from
      Desulfovibrio desulfuricans ATCC 27774: crystallographic and modeling studies of
      oxidized and reduced high-resolution structures at pH 7.6.
AB  - The tetraheme cytochrome c3 is a small metalloprotein with ca. 13,000 Da found in
      sulfate-reducing bacteria, which is believed to act as a partner of hydrogenase.
      The three-dimensional structure of the oxidized and reduced forms of cytochrome
      c3 from Desulfovibrio desulfuricans ATCC 27774 at pH 7.6 were determined using
      high-resolution X-ray crystallography and were compared with the previously
      determined oxidized form at pH 4.0. Theoretical calculations were performed with
      both structures, using continuum electrostatic calculations and Monte Carlo
      sampling of protonation and redox states, in order to understand the molecular
      basis of the redox-Bohr and cooperativity effects related to the coupled transfer
      of electrons and protons. We were able to identify groups that showed redox
      linked conformational changes. In particular, Glu61, His76, and propionate D of
      heme II showed important contributions to the redox-cooperativity, whereas His76,
      propionate A of heme I, and propionate D of heme IV were the key residues for the
      redox-Bohr effect. Upon reduction, an important movement of the backbone region
      surrounding hemes I and II was also identified, that, together with a few redox
      linked conformational changes in side-chain residues, results in a significant
      decrease in the solvent accessibility of hemes I and II.

PMID- 14705031
TI  - Cytosolic domain of the human mitochondrial fission protein fis1 adopts a TPR
      fold.

PMID- 14705032
TI  - Crystal structure of gamma-glutamyl phosphate reductase (TM0293) from Thermotoga
      maritima at 2.0 A resolution.

PMID- 14705033
TI  - X-ray crystal structure of CutA from Thermotoga maritima at 1.4 A resolution.

PMID- 14705034
TI  - Crystal structure of chorismate synthase from Aquifex aeolicus reveals a novel
      beta alpha beta sandwich topology.

PMID- 14705035
TI  - Crystal structure of osmotin, a plant antifungal protein.

PMID- 14705036
TI  - Crystal structure of an iron-containing 1,3-propanediol dehydrogenase (TM0920)
      from Thermotoga maritima at 1.3 A resolution.

PMID- 14705037
TI  - On the 2003 Nobel Prize in medicine or physiology awarded to Paul C. Lauterbur
      and Sir Peter Mansfield.

PMID- 14705038
TI  - B0 dependence of the on-resonance longitudinal relaxation time in the rotating
      frame (T1rho) in protein phantoms and rat brain in vivo.
AB  - On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been
      shown to provide unique information during the early minutes of acute stroke. In
      the present study, the contributions of the different relaxation mechanisms to on
      resonance T1rho relaxation were assessed by determining relaxation rates (R1rho)
      in both protein phantoms and in rat brain at 2.35, 4.7, and 9.4 T. Similar to
      transverse relaxation rate (R2), R1rho increased substantially with increasing
      magnetic field strength (B0). The B0 dependence was more pronounced at weak spin
      lock fields. In contrast to R1rho, longitudinal relaxation rate (R1) decreased as
      a function of increasing B0 field. The present data argue that dipole-dipole
      interaction forms only one pathway for T1rho relaxation and the contributions
      from other physicochemical factors need to be considered.

PMID- 14705039
TI  - Multiple acquisitions with global inversion cycling (MAGIC): a multislice
      technique for vascular-space-occupancy dependent fMRI.
AB  - Recently, a new fMRI technique, termed vascular-space-occupancy (VASO), was
      introduced that uses T1-based blood nulling to detect cerebral blood volume (CBV)
      changes during brain activity. However, similar to other T1-preparation methods,
      this technique is hampered by the fact that there is only one zero-crossing on
      the relaxation curve, presently limiting its application to single-slice studies.
      A multislice VASO-fMRI method is presented that employs a series of nonselective
      180 degrees pulses to periodically invert the magnetization and maintain it
      around zero, while acquiring slices in between. The effects of magnetization
      transfer and signal contamination by stimulated echoes are discussed. Solutions
      to reduce the effect of T1-signal decay as a function of slice number are
      provided. Phantom data show excellent agreement between experiments and numerical
      simulations. Multislice VASO-fMRI images of visual stimulation show effective
      blood nulling in all slices and appropriate functional activations in all
      volunteers (n=4).

PMID- 14705040
TI  - Removal of phase artifacts from fMRI data using a Stockwell transform filter
      improves brain activity detection.
AB  - A novel and automated technique is described for removing fMRI image artifacts
      resulting from motion outside of the imaging field of view. The technique is
      based on the Stockwell transform (ST), a mathematical operation that provides the
      frequency content at each time point within a time-varying signal. Using this
      technique, 1D Fourier transforms (FTs) are performed on raw image data to obtain
      phase profiles. The time series of phase magnitude for each and every point in
      the phase profile is then subjected to the ST to obtain a time-frequency
      spectrum. The temporal location of an artifact is identified based on the
      magnitude of a frequency component relative to the median magnitude of that
      frequency's occurrence over all time points. After each artifact frequency is
      removed by replacing its magnitude with the median magnitude, an inverse ST is
      applied to regain the MR signal. Brain activity detection within fMRI datasets is
      improved by significantly reducing image artifacts that overlap anatomical
      regions of interest. The major advantage of ST-filtering is that artifact
      frequencies may be removed within a narrow time-window, while preserving the
      frequency information at all other time points.

PMID- 14705041
TI  - Signal-to-noise ratio and parallel imaging performance of a 16-channel receive
      only brain coil array at 3.0 Tesla.
AB  - The performance of a 16-channel receive-only RF coil for brain imaging at 3.0
      Tesla was investigated using a custom-built 16-channel receiver. Both the image
      signal-to-noise ratio (SNR) and the noise amplification (g-factor) in sensitivity
      encoding (SENSE) parallel imaging applications were quantitatively evaluated.
      Furthermore, the performance was compared with that of hypothetical coils with
      one, two, four, and eight elements (n) by combining channels in software during
      image reconstruction. As expected, both the g-factor and SNR improved
      substantially with n. Compared to an equivalent (simulated) single-element coil,
      the 16-channel coil showed a 1.87-fold average increase in brain SNR. This was
      mainly due to an increase in SNR in the peripheral brain (an up to threefold SNR
      increase), whereas the SNR increase in the center of the brain was 4%. The
      incremental SNR gains became relatively small at large n, with a 9% gain observed
      when n was increased from 8 to 16. Compared to the (larger) product birdcage head
      coil, SNR increased by close to a factor of 2 in the center, and by up to a
      factor of 6 in the periphery of the brain. For low SENSE acceleration (rate-2), g
      factors leveled off for n>4, and improved only slightly (1.4% averaged over
      brain) going from n=8 to n=16. Improvements in g for n>8 were larger for higher
      acceleration rates, with the improvement for rate-3 averaging 12.0%.

PMID- 14705042
TI  - Extracellular biodegradable macromolecular gadolinium(III) complexes for MRI.
AB  - The clinical application of macromolecular gadolinium (Gd) complexes as MRI
      contrast agents is limited by the slow excretion of Gd(III) complexes and
      consequent long-term tissue accumulation of toxic Gd ions. To alleviate the
      problem of slow excretion, biodegradable polydisulfide-based macromolecular
      Gd(III) complexes were designed and prepared based on the disulfide-thiol
      exchange to allow degradation of the macromolecules by endogenous thiols and to
      facilitate excretion of Gd(III) complexes after the MRI examination. The in vitro
      degradation study showed that the polydisulfide agent was readily degraded by
      cysteine at plasma thiol concentrations. No cross-reaction was observed between
      the cysteine-34 on human serum albumin (HSA) with the agent. Concentration
      dependent blood pool contrast enhancement was observed for the polydisulfide
      agents. The agents of both high molecular weight (35,000 Da) and low molecular
      weight (17,700 Da) produced significant contrast enhancement in the heart and
      aorta in rats at relatively high doses. Except for the bladder, the signal
      intensities gradually decreased over time. Significant blood pool contrast
      enhancement was also observed for the high molecular weight agent at a low dose
      (0.03 mmol-Gd/kg), but not for the agent with a lower molecular weight. The
      contrast enhancement in the urinary bladder increased over time for the
      polydisulfide agents and Gd(III)-(DTPA-BMA). Degradation products were identified
      by mass spectrometry in the urine samples from the rats administered with both
      polydisulfide agents, which confirmed that the polydisulfide agents were degraded
      in vivo and excreted through renal filtration. The preliminary results
      demonstrated the in vitro and in vivo degradability, superior blood pool contrast
      enhancement, and rapid clearance through renal filtration of the novel
      biodegradable macromolecular agent. This agent has a great potential for further
      preclinical and clinical development with application in contrast-enhanced blood
      pool and cancer MR imaging.

PMID- 14705043
TI  - Multicoil Dixon chemical species separation with an iterative least-squares
      estimation method.
AB  - This work describes a new approach to multipoint Dixon fat-water separation that
      is amenable to pulse sequences that require short echo time (TE) increments, such
      as steady-state free precession (SSFP) and fast spin-echo (FSE) imaging. Using an
      iterative linear least-squares method that decomposes water and fat images from
      source images acquired at short TE increments, images with a high signal-to-noise
      ratio (SNR) and uniform separation of water and fat are obtained. This algorithm
      extends to multicoil reconstruction with minimal additional complexity. Examples
      of single- and multicoil fat-water decompositions are shown from source images
      acquired at both 1.5T and 3.0T. Examples in the knee, ankle, pelvis, abdomen, and
      heart are shown, using FSE, SSFP, and spoiled gradient-echo (SPGR) pulse
      sequences. The algorithm was applied to systems with multiple chemical species,
      and an example of water-fat-silicone separation is shown. An analysis of the
      noise performance of this method is described, and methods to improve noise
      performance through multicoil acquisition and field map smoothing are discussed.

PMID- 14705044
TI  - TurboFLASH FAIR imaging with optimized inversion and imaging profiles.
AB  - Optimal implementation of pulsed arterial spin labeling (PASL) methods such as
      flow-sensitive alternating inversion recovery (FAIR), require the minimization of
      interactions between the inversion and imaging slabs. For FAIR, the
      inversion:imaging slice thickness ratio (STR) is usually at least 3:1 in order to
      fully contain the extent of the imaging slice. The resulting gap exacerbates the
      transit time. So far, efforts to minimize the STR have concentrated on the
      inversion profile. However, the imaging profile remains a limiting factor
      especially for rapid sequences such as turbo fast low-angle shot (TurboFLASH)
      which uses short pulses. This study reports the implementation of a TurboFLASH
      sequence with optimized inversion and imaging profiles. Slice-selection is
      achieved with a preparation module incorporating a pair of identical adiabatic
      frequency offset corrected inversion (FOCI) pulses. The optimum radiofrequency
      (RF) and gradient scheme for this pulse combination is described, and the
      relaxation characteristics of the slice-selection scheme are investigated.
      Phantom experiments demonstrate a reduction in the STR to approximately 1.13:1.
      Implementation in an animal model is described, and the benefit of the improved
      profile in probing the sensitivity of the flow signal to tagging geometry is
      demonstrated. Sensitivity to transit time effects can be minimized with this
      sequence, and ASL methodologies can be better explored as a result of the
      improved conformance with the ideal of square slice profiles.

PMID- 14705045
TI  - Monitoring angiogenesis in brain using steady-state quantification of DeltaR2
      with MION infusion.
AB  - An MRI method for quantification of cerebral blood volume (CBV) in time-course
      studies of angiogenesis is described. Angiogenesis was stimulated by acclimation
      to hypoxia. The change in relaxation rate, R2, which is relatively sensitive to
      the microvasculature, was quantified before and after infusion of a
      superparamagnetic vascular contrast agent (MION). The DeltaR2 was measured in
      serum and brain parenchyma with a multiecho sequence. In vitro and in vivo
      calibration curves of MION concentration vs. R2 were approximated by a linear
      function. CBV was 3.14 +/- 0.32% (mean +/- SE, n=13) and 6.42 +/- 0.54% (n=4)
      before and after acclimation. A second acclimated group was hemodiluted to
      control for polycythemia. CBV was not significantly different between hemodiluted
      and nonhemodiluted groups. In animals where NMR measurements were taken before
      and after acclimation, there was a 120% increase in CBV. The NMR technique was
      validated using quantitative morphometrics, which showed an increase of 147% in
      CBV with acclimation. We found a linear correlation between MRI and the
      morphometric results for CBV, as well as demonstrating a quantitative equivalence
      for relative changes in CBV. This article describes a simple, repeatable method
      of imaging brain microvascular volume using a plasma-based contrast agent that
      can be applied to longitudinal studies of angiogenesis.

PMID- 14705046
TI  - High-resolution myocardial perfusion mapping in small animals in vivo by spin
      labeling gradient-echo imaging.
AB  - An ECG and respiration-gated spin-labeling gradient-echo imaging technique is
      proposed for the quantitative and completely noninvasive measurement and mapping
      of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH
      imaging, the spatial resolution of the perfusion maps is not limited by the heart
      rate. A significant improvement in image quality is achieved by synchronizing the
      inversion pulse to the respiration movements of the animals, thereby allowing for
      spontaneous respiration. High-resolution myocardial perfusion maps (in-plane
      resolution=234 x 468 microm2) demonstrating the quality of the perfusion
      measurement were obtained at 4.7 T in a group of seven freely breathing Wistar
      Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average
      +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion
      was mapped and measured under cardiac dobutamine stress. Perfusion increased to
      11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the
      study of small rodents at high fields.

PMID- 14705047
TI  - Calculation of flip angles for echo trains with predefined amplitudes with the
      extended phase graph (EPG)-algorithm: principles and applications to hyperecho
      and TRAPS sequences.
AB  - The article presents an algorithm for calculation of flip angles in multiecho
      experiments to generate echoes with predefined amplitudes based on the extended
      phase graph algorithm. The algorithm can be used to optimize the echo envelope
      and thus the point spread function (PSF) in hyperecho and TRAPS (transition into
      the pseudosteady state) experiments while minimizing the total RF power.
      Implementations at 3 T using echo trains with Gaussian and Lorentzian PSF
      demonstrate a reduction in RF power by a factor of 3-5 while maintaining high
      image quality.

PMID- 14705048
TI  - Time-optimal multidimensional gradient waveform design for rapid imaging.
AB  - Magnetic resonance imaging (MRI) is limited in many cases by long scan times and
      low spatial resolution. Recent advances in gradient systems hardware allow very
      rapid imaging sequences, such as steady-state free precession (SSFP), which has
      repetition times (TRs) of 2-5 ms. The design of these rapid sequences demands
      time-optimal preparatory gradient waveforms to provide maximum readout duty
      cycle, and preserve spatial resolution and SNR while keeping TRs low. Time
      optimal gradient waveforms can be synthesized analytically for certain simple
      cases. However, certain problems, such as time-optimal 2D and 3D gradient design
      with moment constraints, either may not have a solution or must be solved
      numerically. We show that time-optimal gradient design is a convex-optimization
      problem, for which very efficient solution methods exist. These methods can be
      applied to solve gradient design problems for oblique gradient design, spiral
      imaging, and flow-encoding using either a constant slew rate or the more exact
      voltage-limited gradient models. Ultimately, these methods provide a time-optimal
      solution to many 2D and 3D gradient design problems in a sufficiently short time
      for interactive imaging.

PMID- 14705049
TI  - Self-gated cardiac cine MRI.
AB  - The need for ECG gating presents many difficulties in cardiac magnetic resonance
      imaging (CMRI). Real-time imaging techniques eliminate the need for ECG gating in
      cine CMRI, but they cannot offer the spatial and temporal resolution provided by
      segmented acquisition techniques. Previous MR signal-based techniques have
      demonstrated an ability to provide cardiac gating information; however, these
      techniques result in decreased imaging efficiency. The purpose of this work was
      to develop a new "self-gated" (SG) acquisition technique that eliminates these
      efficiency deficits by extracting the motion synchronization signal directly from
      the same MR signals used for image reconstruction. Three separate strategies are
      proposed for deriving the SG signal from data acquired using radial k-space
      sampling: echo peak magnitude, kymogram, and 2D correlation. The SG techniques
      were performed on seven normal volunteers. A comparison of the results showed
      that they provided cine image series with no significant differences in image
      quality compared to that obtained with conventional ECG gating techniques. SG
      techniques represent an important practical advance in clinical MRI because they
      enable the acquisition of high temporal and spatial resolution cardiac cine
      images without the need for ECG gating and with no loss in imaging efficiency.

PMID- 14705050
TI  - Comprehensive approach for correction of motion and distortion in diffusion
      weighted MRI.
AB  - Patient motion and image distortion induced by eddy currents cause artifacts in
      maps of diffusion parameters computed from diffusion-weighted (DW) images. A
      novel and comprehensive approach to correct for spatial misalignment of DW
      imaging (DWI) volumes acquired with different strengths and orientations of the
      diffusion sensitizing gradients is presented. This approach uses a mutual
      information-based registration technique and a spatial transformation model
      containing parameters that correct for eddy current-induced image distortion and
      rigid body motion in three dimensions. All parameters are optimized
      simultaneously for an accurate and fast solution to the registration problem. The
      images can also be registered to a normalized template with a single
      interpolation step without additional computational cost. Following registration,
      the signal amplitude of each DWI volume is corrected to account for size
      variations of the object produced by the distortion correction, and the b
      matrices are properly recalculated to account for any rotation applied during
      registration. Both qualitative and quantitative results show that this approach
      produces a significant improvement of diffusion tensor imaging (DTI) data
      acquired in the human brain.

PMID- 14705051
TI  - Flow artifacts in steady-state free precession cine imaging.
AB  - Steady-state free precession (SSFP) cardiac cine images are frequently corrupted
      by dark flow artifacts, which can usually be eliminated by reshimming and
      retuning the scanner. A theoretical explanation for these artifacts is provided
      in terms of spins moving through an off-resonant point in the magnetic field, and
      the theory is validated using phantom experiments. The artifacts can be
      reproduced in vivo by detuning the center frequency by an amount in the range of
      half the inverse repetition time (TR). Since this offset is similar in magnitude
      to the frequency difference between the water and lipid peaks, a likely cause of
      the artifacts in vivo is that the center frequency is tuned incorrectly to the
      lipid peak rather than the water peak.

PMID- 14705052
TI  - On the calculation and interpretation of signal intensity in echo-shifted
      sequences.
AB  - Echo-shifted sequences have been shown to be useful in applications where strong
      T*2-weighting and short repetition times are wanted, such as BOLD-contrast fMRI,
      MR thermometry, and perfusion studies. However, a full understanding of signal
      formation with such methods, which is mandatory to optimize sequence parameters
      for particular applications, has still not been achieved. Here, two methods are
      proposed to calculate the steady-state signal intensity in coherent TR-periodic
      and TR-shifted gradient-echo sequences. The integration method, which consists of
      averaging the steady-state magnetization over all isochromats in a voxel, is
      shown to be a particularly efficient way of obtaining the analytical expression
      of the measurable signal. The partition method, based on a physical decomposition
      of the steady-state magnetization into a sum of contributions from past
      excitation pulses, reveals that the net transverse magnetization results from a
      destructive interference between the wanted component and a series of stimulated
      echoes. The analysis includes off-resonance effects and is illustrated by phantom
      measurements. Relationships with previous publications on this subject are
      discussed.

PMID- 14705053
TI  - Increase in left ventricular torsion-to-shortening ratio in children with
      valvular aortic stenosis.
AB  - Perfusion of left ventricular (LV) subendocardium in valvular aortic stenosis
      (AS) patients is impaired. It was expected that this may lead to a reduction of
      subendocardial fiber contraction and, consequently, to an increase of LV torsion
      per amount of ejection. Using MR tagging (MRT), it was investigated whether the
      torsion-to-shortening ratio (TSR) is elevated in valvular AS patients. Six
      asymptomatic children with valvular AS were investigated using echo Doppler, ECG,
      exercise test, and MRT. LV torsion and natural strain of the inner diameter were
      determined from measured tag displacements in two short-axis slices of the LV. In
      all AS patients TSR was approximately 40% increased (0.62 +/- 0.04 rad; mean +/-
      SD) as compared to pediatric (0.44 +/- 0.08 rad; n=5) and adult controls (0.46 +/
      0.08 rad; n=9), indicating subendocardial contractile dysfunction. With other
      techniques hitherto used this type of dysfunction could not be detected.

PMID- 14705054
TI  - Visualization and analysis of white matter structural asymmetry in diffusion
      tensor MRI data.
AB  - This work presents a method that permits the characterization, quantification,
      and 3D visualization of white matter structural information contained within
      diffusion tensor MR imaging (DT-MRI) data. In this method, regions within the
      brain are defined as possessing linear, planar, or spherical diffusion.
      Visualization of this diffusion metric data is realized by generating streamtube
      and streamsurface models to represent regions of linear and planar diffusion.
      Quantification of differences in diffusion anisotropy between different regions
      of interest (ROIs) is then achieved by analyzing 2D barycentric histograms
      created from the complete distribution of diffusion metric values measured in
      each region. In four healthy volunteers, there was only a small degree of
      asymmetry (epsilon) in the number of linear, planar, or spherical diffusion
      voxels between the right and left hemispheres (epsilon approximately equal to +/-
      2%). However, in a patient with a metastatic brain lesion there was marked
      asymmetry in both linear (epsilon approximately -10%) and planar (epsilon
      approximately equal to 5%) diffusion between comparable ipsilateral and
      contralateral regions, with a significant reduction in the number of linear
      diffusion voxels and an increase in the number of planar diffusion voxels in the
      tumor-bearing hemisphere. These results demonstrate the potential of this
      approach to characterize brain structure in both healthy and diseased subjects.

PMID- 14705055
TI  - Optimizing the sequence parameters for double-quantum CRAZED imaging.
AB  - The evolution of magnetization during repeated application of the double-quantum
      (DQ)-CRAZED sequence is analyzed, with the aim of identifying sequence parameters
      that maximize sensitivity to signal produced by the distant dipole field (DDF).
      Phase cycling schemes that allow cancellation of signals following undesired
      coherence pathways are also described. Simulations and imaging experiments
      carried out at 3 T on phantoms and the human head were used to verify the
      analysis. The results indicate that in the absence of phase cycling, the DDF
      related signal-to-noise ratio (SNR) per unit time is maximized using TR=2.05 T1,
      along with values of the RF flip angles (alpha approximately 90 degrees and beta
      approximately 60 degrees ), and echo time (TE=T2) that have previously been shown
      to maximize the DDF-related signal at long TR. However, with TR=2.05 T1 there can
      also be a significant signal contribution due to stimulated echo effects (up to
      40% of the signal for water at 3 T and TE=70 ms). Using a two-step phase cycle,
      the stimulated echo signal is eliminated and the maximum SNR per unit time occurs
      for TR=2.76 T1. It is also demonstrated that sensitivity to signal changes caused
      by small variations in T2 is maximized by setting TE=2T2.

PMID- 14705056
TI  - Momentum-weighted conjugate gradient descent algorithm for gradient coil
      optimization.
AB  - MRI gradient coil design is a type of nonlinear constrained optimization. A
      practical problem in transverse gradient coil design using the conjugate gradient
      descent (CGD) method is that wire elements move at different rates along
      orthogonal directions (r, phi, z), and tend to cross, breaking the constraints. A
      momentum-weighted conjugate gradient descent (MW-CGD) method is presented to
      overcome this problem. This method takes advantage of the efficiency of the CGD
      method combined with momentum weighting, which is also an intrinsic property of
      the Levenberg-Marquardt algorithm, to adjust step sizes along the three
      orthogonal directions. A water-cooled, 12.8 cm inner diameter, three axis torque
      balanced gradient coil for rat imaging was developed based on this method, with
      an efficiency of 2.13, 2.08, and 4.12 mT.m(-1).A(-1) along X, Y, and Z,
      respectively. Experimental data demonstrate that this method can improve
      efficiency by 40% and field uniformity by 27%. This method has also been applied
      to the design of a gradient coil for the human brain, employing remote current
      return paths. The benefits of this design include improved gradient field
      uniformity and efficiency, with a shorter length than gradient coil designs using
      coaxial return paths.

PMID- 14705057
TI  - Scalable multichannel MRI data acquisition system.
AB  - A scalable multichannel digital MRI receiver system was designed to achieve high
      bandwidth echo-planar imaging (EPI) acquisitions for applications such as BOLD
      fMRI. The modular system design allows for easy extension to an arbitrary number
      of channels. A 16-channel receiver was developed and integrated with a General
      Electric (GE) Signa 3T VH/3 clinical scanner. Receiver performance was evaluated
      on phantoms and human volunteers using a custom-built 16-element receive-only
      brain surface coil array. At an output bandwidth of 1 MHz, a 100% acquisition
      duty cycle was achieved. Overall system noise figure and dynamic range were
      better than 0.85 dB and 84 dB, respectively. During repetitive EPI scanning on
      phantoms, the relative temporal standard deviation of the image intensity time
      course was below 0.2%. As compared to the product birdcage head coil, 16-channel
      reception with the custom array yielded a nearly 6-fold SNR gain in the cerebral
      cortex and a 1.8-fold SNR gain in the center of the brain. The excellent system
      stability combined with the increased sensitivity and SENSE capabilities of 16
      channel coils are expected to significantly benefit and enhance fMRI
      applications.

PMID- 14705058
TI  - Lumped-element planar strip array (LPSA) for parallel MRI.
AB  - The recently introduced planar strip array (PSA) can significantly reduce scan
      times in parallel MRI by enabling the utilization of a large number of RF strip
      detectors that are inherently decoupled, and are tuned by adjusting the strip
      length to integer multiples of a quarter-wavelength (lambda/4) in the presence of
      a ground plane and dielectric substrate. In addition, the more explicit spatial
      information embedded in the phase of the signals from the strip array is
      advantageous (compared to loop arrays) for limiting aliasing artifacts in
      parallel MRI. However, losses in the detector as its natural resonance frequency
      approaches the Larmor frequency (where the wavelength is long at 1.5 T) may limit
      the signal-to-noise ratio (SNR) of the PSA. Moreover, the PSA's inherent lambda/4
      structure severely limits our ability to adjust detector geometry to optimize the
      performance for a specific organ system, as is done with loop coils. In this
      study we replaced the dielectric substrate with discrete capacitors, which
      resulted in both SNR improvement and a tunable lumped-element PSA (LPSA) whose
      dimensions can be optimized within broad constraints, for a given region of
      interest (ROI) and MRI frequency. A detailed theoretical analysis of the LPSA is
      presented, including its equivalent circuit, electromagnetic fields, SNR, and g
      factor maps for parallel MRI. Two different decoupling schemes for the LPSA are
      described. A four-element LPSA prototype was built to test the theory with
      quantitative measurements on images obtained with parallel and conventional
      acquisition schemes.

PMID- 14705059
TI  - Frame-by-frame PRESS 1H-MRS of the brain at 3 T: the effects of physiological
      motion.
AB  - 1H-MRS at high field has been increasingly utilized to study brain metabolism in
      healthy and pathological states. The aim of this work was to determine the
      effects of physiological motion on the results of this exam in the presence of
      the increased susceptibility differences at high field. Single voxel spectra of
      various regions in the human brain were acquired using frame-by-frame PRESS 1H
      MRS at a 0.5 Hz sampling rate. The frame-by-frame variations of the FID phase and
      the frequency and fractional amplitude variations of the residual water-signal
      were analyzed. In the human brain the standard deviations of these variations
      were 3.9 +/- 0.5 degrees, 0.83 +/- 0.32 Hz, and 0.028 +/- 0.013 of the mean
      amplitude (n=15). In a motionless phantom, smaller phase and frequency variations
      were detected in water-suppressed acquisitions. However, the end effects of
      physiological motion on PRESS 1H-MRS of the brain at 3 T were negligible.

PMID- 14705060
TI  - Eddy current correction in diffusion-weighted imaging using pairs of images
      acquired with opposite diffusion gradient polarity.
AB  - In echo-planar-based diffusion-weighted imaging (DWI) and diffusion tensor
      imaging (DTI), the evaluation of diffusion parameters such as apparent diffusion
      coefficients and anisotropy indices is affected by image distortions that arise
      from residual eddy currents produced by the diffusion-sensitizing gradients.
      Correction methods that coregister diffusion-weighted and non-diffusion-weighted
      images suffer from the different contrast properties inherent in these image
      types. Here, a postprocessing correction scheme is introduced that makes use of
      the inverse characteristics of distortions generated by gradients with reversed
      polarity. In this approach, only diffusion-weighted images with identical
      contrast are included for correction. That is, non-diffusion-weighted images are
      not needed as a reference for registration. Furthermore, the acquisition of an
      additional dataset with moderate diffusion-weighting as suggested by Haselgrove
      and Moore (Magn Reson Med 1996;36:960-964) is not required. With phantom data it
      is shown that the theoretically expected symmetry of distortions is preserved in
      the images to a very high degree, demonstrating the practicality of the new
      method. Results from human brain images are also presented.

PMID- 14705061
TI  - Determination of optimal angles for variable nutation proton magnetic spin
      lattice, T1, and spin-spin, T2, relaxation times measurement.
AB  - T1 and T2 can be rapidly determined with a combination of multiangle spoiled
      gradient recalled echo (SPGR) and steady-state free precession (SSFP) imaging.
      Previously, we demonstrated a simple method for determining the set of SPGR and
      SSFP angles that provided greater T1 and T2 precision than a set of uniformly
      spaced angles. In this article a more rigorous approach for determining angles is
      described. Weighted least-squares is also introduced for T1 and T2 estimation and
      a novel weighting function described. This new approach, suited for imaging
      applications where large T1 and T2 ranges are anticipated, provides high and
      uniform precision over a wide range of T1 and T2 values.

PMID- 14705062
TI  - Extended coverage first-pass perfusion imaging using slice-interleaved TSENSE.
AB  - Parallel imaging applied to first-pass, contrast-enhanced cardiac MR can yield
      greater spatial coverage for a fixed temporal resolution. The method combines
      rate R=2 acceleration using TSENSE with shot-to-shot interleaving of two slices.
      The square root R SNR loss is largely compensated for by a longer effective
      repetition time (TR) and increased flip angle associated with slice interleaving.
      In this manner, increased spatial coverage is achieved while comparable or better
      image quality is maintained. Single-heartbeat temporal resolution was
      accomplished with spatial coverage of eight slices at heart rates up to 71 bpm,
      six slices up to 95 bpm, and four slices up to 143 bpm. Experiments in normal
      subjects (N=6) were performed to assess signal-to-noise ratio (SNR) and contrast
      to-noise ratio (CNR) values.

PMID- 14705063
TI  - FASCINATE: a pulse sequence for simultaneous acquisition of T2-weighted and fluid
      attenuated images.
AB  - A pulse sequence that enables simultaneous acquisition of T2-weighted and fluid
      attenuated images is presented. This sequence is referred to as FASCINATE (Fluid
      Attenuated Scan Combined with Interleaved Non-ATtEnuation). In this new
      technique, the inversion pulse of conventional fast fluid-attenuated inversion
      recovery (FLAIR) is replaced with a fast spin echo (FSE) acquisition that has an
      additional 180(y)-90(x) pulse train for driven inversion. By using appropriate
      scan parameters, the first part of the sequence provides T2-weighted images and
      the second part provides fluid-attenuated images, thus allowing simultaneous
      acquisition in a single scan time comparable to that of fast FLAIR. FASCINATE was
      compared with conventional scanning techniques using a normal volunteer and a
      patient. A signal simulation was also conducted. In the human study, both T2
      weighted and fluid-attenuated images from FASCINATE showed the same image quality
      as conventional images, suggesting the potential for this technique to replace
      the combination of fast FLAIR and T2-weighted FSE for scan time reduction.

PMID- 14705064
TI  - Simultaneous acquisition of gradient-echo and asymmetric spin-echo for single
      shot z-shim: Z-SAGA.
AB  - This article describes the Z-SAGA pulse sequence, a technique for recovering
      susceptibility losses in EPI images for neuroimaging applications. The pulse
      sequence is based on an asymmetric spin echo EPI sequence and acquires a gradient
      echo image and an asymmetric spin echo image in a single shot. For one of the
      images, a z-shim gradient pulse is applied to compensate for susceptibility
      related field distortions. The two images are combined to form an image with
      reduced signal loss. This sequence is simple to implement and experimentally
      demonstrated to be effective for BOLD imaging.

PMID- 14705065
TI  - Effects of end-ring/shield configuration on homogeneity and signal-to-noise ratio
      in a birdcage-type coil loaded with a human head.
AB  - We modeled four different end-ring/shield configurations of a birdcage coil to
      examine their effects on field homogeneity and signal-to-noise ratio (SNR) at 64
      MHz and 125 MHz. The configurations are defined as: 1) conventional: a
      conventional cylindrical shield; 2) surrounding shield: a shield with annular
      extensions to closely shield the end rings; 3) solid connection: a shield with
      annular extensions connected to the rungs; and 4) thin wire connection: a shield
      with thin wires connected to the rungs. At both frequencies, the coil with
      conventional end-ring/shield configuration produces the most homogeneous RF
      magnetic (B1) field when the coil is empty, but produces the least homogeneous B1
      field when the coil is loaded with a human head. The surrounding shield
      configuration results in the most homogeneous B1 and highest SNR in the coil
      loaded with the human head at both frequencies, followed closely by the solid
      connection configuration.

PMID- 14705068
TI  - Is it worth it?

PMID- 14705069
TI  - The seventh congress of the Chinese Society of Microsurgery.

PMID- 14705070
TI  - Microsurgical treatment for bilateral thumb defect: five case reports.
AB  - The authors present a new and efficient treatment for reconstruction of bilateral
      defective thumbs by different configured toe-tissues transplantations in a single
      stage, including bilateral second-toe transfer in 2 cases, bilateral hallux wrap
      around flap transfer in 1 case, bilateral modified hallux wrap-around flap
      transfer in 1 case, and combined second toe with island flap with neurovascular
      pedicles from the proximal and dorsal aspect of the index finger transfer in 1
      case. In total, eight transferred tissues survived uneventfully after circulation
      monitor and medicine administration according to the rules of microsurgery, and
      in two other transferred toe tissues, temporary circulation crises occurred. Over
      a 1-year follow-up, the satisfactory appearance and excellent function of the
      reconstructed bilateral thumbs were noted. For ensuring the success of the
      procedure, the authors emphasize the establishment of a double artery supply and
      venous return-flow systems and the modification of the hallux wrap-around flap
      dissection and tendon repair. Meanwhile, three-stage systemically functional
      rehabilitations also improved functional restoration of reconstructed thumbs.

PMID- 14705071
TI  - Comparison of different managements of large superficial veins in distally based
      fasciocutaneous flaps with a veno-neuro-adipofascial pedicle: an experimental
      study using a rabbit model.
AB  - The role of large superficial veins in the survival of a distally based
      fasciocutaneous flap with a veno-neuro-adipofascial pedicle was studied in a
      rabbit model. A sural veno-neuro-fasciocutaneous flap model (6 x 2 cm) with a
      distally based lesser saphenous veno-neuro-adipofascial pedicle (1.5 cm) was
      established. Fifteen rabbits were randomly divided into three groups with 10
      flaps in each group. In group I, the distal lesser saphenous vein was left open
      (venous inflow remained) after the flap was raised. In group II, the lesser
      saphenous vein was ligated in the pedicle (no venous inflow). In group III, the
      venous pedicle was left open in the pedicle, and the proximal end was
      microsurgically anastomosed to the recipient vein (outflow established).
      Intravenous pressure, flap survival, and histology were examined. The results
      showed that the values of intravenous pressure in group I were significantly
      higher than in group II (P < 0.001). The mean flap survival rate of group III
      (94.5%) was significantly higher (P < 0.001) than of groups I (22.7%) and II
      (55.5%). Histology showed that the lesser saphenous vein in group I was extremely
      dilated and filled with thrombosis. This experiment demonstrated that
      establishing a superficial venous outflow channel by anastomosis at the proximal
      end, or interrupting the inflow channel by ligation at the distal pedicle, may
      significantly improve the survival rate of distally based veno-neuro
      fasciocutaneous flaps.

PMID- 14705072
TI  - C1-esterase inhibitor and a novel peptide inhibitor improve contractile function
      in reperfused skeletal muscle.
AB  - To determine the role of inhibition of complement activation in the contractile
      function of skeletal muscle ischemia-reperfusion (I/R) injury, the rat extensor
      digitorum longus (EDL) muscles underwent 3 h ischemia and received human C1
      esterase inhibitor (C1-INH, 100 IU/kg), a synthetic C1q A chain peptide with a
      similar inhibitory effect on activated C1 (peptide, 5 mg/kg), or human serum
      albumin control. Results showed a significant overall increase in tetanic
      contractile forces of the reperfused EDL in both C1-INH and peptide groups
      compared to controls. Maximum improvement occurred with peptide treatment at 120
      Hz stimulation, with an increase in force from 38 +/- 4% of normal in controls to
      52 +/- 4% in peptide-treated rats. There were no significant differences between
      C1-INH and peptide groups. Plasma C3 and C4 activities were significantly
      increased in both treated groups, suggesting inhibition of complement activation.
      Our results suggest that complement activation is involved in I/R injury, and
      inhibition of complement activation may therefore represent a potential
      therapeutic approach to reducing or preventing I/R injury.

PMID- 14705073
TI  - Administration of bone marrow cells into surgically induced fibrocollagenous
      tunnels induces angiogenesis in ischemic rat hindlimb model.
AB  - We established a comparative model of angiogenic induction in previously formed
      fibrocollagenous tunnels in rat inner thigh muscles. A unilateral hindlimb
      chronic ischemia model was performed in male Sprague-Dawley rats. A device was
      then inserted in the central portion of the inner thigh muscles. Vascularity in
      the ischemic limb was determined by means of an angiographic score,
      capillary/fiber ratio, and endothelial proliferation by histochemistry and
      immunohistochemistry. Autologous transplant of bone marrow, vascular endothelial
      growth factor (VEGF), or collagen-polyvinylpyrrolidone plus heparin induced
      significant vascularization of the ischemic hindlimb when compared to saline
      solution. However, the bone marrow group presented a higher angiographic score
      than the other two. No differences among groups were observed in capillary/fiber
      ratio or proliferation, except for the VEGF group, where capillary proliferating
      cells were significantly higher than in controls. Based on these results, bone
      marrow-derived progenitor cells may constitute a safe and viable alternative for
      the induction of therapeutic angiogenesis.

PMID- 14705074
TI  - Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats.
AB  - The purpose of this experimental study was to investigate the effects of topical
      applications of hyaluronic acid on peripheral nerve scarring and regeneration in
      an adult rat model. After the right sciatic nerves of 48 rats were transected and
      immediately repaired, nerves were randomly divided into two groups. Nerves to
      which were applied hyaluronic acid comprised the experimental group, and nerves
      to which were applied saline comprised the control group. Perineural scarring was
      evaluated at 4 and 12 weeks macroscopically and histologically. Nerves treated
      with hyaluronic acid demonstrated significant reduction in perineural scar
      thickness (P < 0.05, Student's t-test). Histomorphologic nerve analysis,
      electrophysiologic studies, muscle mass evaluation, and serial functional walking
      track analysis were performed for evaluation of peripheral nerve regeneration at
      12 weeks. The results showed better conduction velocities, increased axon-fiber
      diameter, and faster functional recovery in hyaluronic acid-treated nerves (P <
      0.05, Student's t-test). In conclusion, hyaluronic acid appears to be effective
      in preventing perineural scar formation, resulting in enhancement of peripheral
      nerve regeneration.

PMID- 14705075
TI  - New experimental composite flap model in rats: gluteus maximus-tensor fascia lata
      osteomuscle flap.
AB  - Experimental animal models need to be developed for studies of composite flaps
      that have often recently been used for defects of both bone and soft tissues. A
      consistent anatomy, simple surgical technique, and reliable blood flow are
      essential for the success of experimental flap studies. Here we propose a gluteus
      maximus-tensor fascia lata osteomuscle flap in rats as a model of these
      qualities. Gluteus maximus and tensor fascia lata muscles and the adjacent iliac
      bone segment were combined as a lateral circumflex femoral artery-based flap. To
      test the reliability of this composite flap, three types of composite tissues
      were harvested and replaced: osteomusculocutaneous flap, osteomuscle flap, and
      osteomuscle composite graft. The osteomusculocutaneous flap was elevated by
      including a skin island over the gluteal region. The osteomuscle graft was formed
      by deliberately dividing the vascular pedicle of the osteomuscle flap. Direct
      observation revealed complete necrosis of the skin islands in all
      osteomusculocutaneous flaps. Microangiography of the flap demonstrated that both
      muscles and the attached bone were supplied by the pedicle. Dye studies with
      nitro blue tetrazolium (NBT) and India ink demonstrated dye uptake in both muscle
      and bone components in osteomuscle flaps. Histological examinations also
      demonstrated the viability of both tissues only in the flap group. Bone
      scintigraphy performed in flaps on postoperative day 7 demonstrated radionuclide
      uptake, confirming perfusion of the bony segment. The gluteus maximus-tensor
      fascia lata osteomuscle flap is a reliable and simple model for composite flap
      studies that offers the following advantages: 1) it is a new composite flap which
      includes bone, 2) it can be dissected easily with the naked eye, without using
      the microscope, 3) it has a long pedicle for flap displacement, and 4) it is a
      small animal model.

PMID- 14705078
TI  - Highly branched macromolecules at the interface of chemistry, biology, physics,
      and medicine.

PMID- 14705079
TI  - Supramolecular drug-delivery systems based on polymeric core-shell architectures.

PMID- 14705080
TI  - Chiral tertiary alcohols made by catalytic enantioselective addition of
      unreactive zinc reagents to poorly electrophilic ketones?

PMID- 14705081
TI  - NMR spectroscopy tools for structure-aided drug design.
AB  - Biomolecular NMR spectroscopy has expanded dramatically in recent years and is
      now a powerful tool for the study of structure, dynamics, and interactions of
      biomolecules. Previous limitations with respect to molecular size are no longer a
      primary barrier, and systems as large as 900 kDa were recently studied. NMR
      spectroscopy is already well-established as an efficient method for ligand
      screening. A number of recently developed techniques show promise as aids in
      structure-based drug design, for example, in the rapid determination of global
      protein folds, the structural characterization of ligand-protein complexes, and
      the derivation of thermodynamic parameters. An advantage of the method is that
      all these interactions can be studied in solution--time-consuming crystallization
      is not necessary. This Review focuses on recent developments in NMR spectroscopy
      and how they might be of value in removing some of the current "bottlenecks" in
      structure-based drug discovery.

PMID- 14705082
TI  - [Ga51(PtBu2)14Br6]3-: an elementoid gallium cluster with metalloid and
      nonmetalloid structural elements.

PMID- 14705083
TI  - Syntheses and crystal structures of the Ag[bond]S cluster compounds
      [Ag70S20(SPh)28(dppm)10] (CF3CO2)2 and [Ag262S100(StBu)62(dppb)6].

PMID- 14705085
TI  - Desymmetrization of metalated cyclohexadienes and application to the synthesis of
      nephrosteranic acid.

PMID- 14705084
TI  - Formation of a unique ansa-metallocene framework by intramolecular photochemical
      [2+2] cycloaddition of bis(2-alkenylindenyl)zirconium complexes.

PMID- 14705086
TI  - Efficient synthesis of chiral alpha- and beta-hydroxy amides: application to the
      synthesis of (R)-fluoxetine.

PMID- 14705087
TI  - Difluorphos, an electron-poor diphosphane: a good match between electronic and
      steric features.

PMID- 14705088
TI  - Regioselective postsynthetic modification of phenylalanine side chains of
      peptides leading to uncommon ortho-iodinated analogues.

PMID- 14705089
TI  - Parallel fragment assembly strategy towards multiple-ether mimicry of anticancer
      annonaceous acetogenins.

PMID- 14705090
TI  - Synthesis, structure, and greatly improved reversible O2 binding in a
      structurally modulated micro-eta 2:eta 2-peroxodicopper(II) complex with room
      temperature stability.

PMID- 14705091
TI  - 2-Dimethylarsinothioyl acetic acid identified in a biological sample: the first
      occurrence of a mammalian arsinothioyl metabolite.

PMID- 14705092
TI  - Chelation-controlled intermolecular hydroacylation: direct addition of alkyl
      aldehydes to functionalized alkenes.

PMID- 14705093
TI  - N-trialkylsilylimines as coupling partners for pd-catalyzed C[bond]N-forming
      reactions: one-step synthesis of imines and azadienes from aryl and alkenyl
      bromides.

PMID- 14705094
TI  - Mixed transition-metal-lanthanide complexes at higher oxidation states:
      heteronuclear CeIV-MnIV clusters.

PMID- 14705095
TI  - Micrometer-sized hexagonal tubes self-assembled by a cyclic peptide in a liquid
      crystal.

PMID- 14705096
TI  - Palladium-catalyzed oxidative kinetic resolution with ambient air as the
      stoichiometric oxidation gas.

PMID- 14705097
TI  - Reversible switching between superhydrophilicity and superhydrophobicity.

PMID- 14705098
TI  - Photoinduced vectorial charge transfer across walls of hollow microcapsules.

PMID- 14705099
TI  - Accelerated diffusion of long-chain alkanes between nanosized cavities.

PMID- 14705100
TI  - Synthesis and light-emitting characteristics of doughnut-shaped pi-electron
      systems.

PMID- 14705101
TI  - Writing patterns of molecules on molecular printboards.

PMID- 14705105
TI  - Spinal cord stimulation for chronic reflex sympathetic dystrophy.

PMID- 14705106
TI  - Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency.
AB  - Glutaryl-CoA dehydrogenase deficiency is an inherited organic aciduria with
      predominantly neurological presentation. Biochemically, it is characterized by an
      accumulation and enhanced urinary excretion of two key organic acids, glutaric
      acid and 3-hydroxyglutaric acid. If untreated, acute striatal degeneration is
      often precipitated by febrile illnesses during a vulnerable period of brain
      development in infancy or early childhood, resulting in a dystonic dyskinetic
      movement disorder. The mechanism underlying these acute encephalopathic crises
      has been partially elucidated using in vitro and in vivo models. 3
      Hydroxyglutaric and glutaric acids share structural similarities with the main
      excitatory amino acid glutamate and are considered to play an important role in
      the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic
      cell damage specifically via activation of N-methyl-D-aspartate receptors.
      Furthermore, glutaric and 3-hydroxyglutaric acids indirectly modulate
      glutamatergic and GABAergic neurotransmission, resulting in an imbalance of
      excitatory and inhibitory neurotransmission. It also has been suggested that
      secondary amplification loops potentiate the neurotoxic properties of these
      organic acids. Probable mechanisms for this effect include cytokine-stimulated
      nitric oxide production, a decrease in energy metabolism, and reduction of
      cellular creatine phosphate levels. Finally, maturation-dependent changes in the
      expression of neuronal glutamate receptors may affect the vulnerability to 3
      hydroxyglutaric and glutaric acid toxicity.

PMID- 14705107
TI  - The effect of spinal cord stimulation in patients with chronic reflex sympathetic
      dystrophy: two years' follow-up of the randomized controlled trial.
AB  - Chronic reflex sympathetic dystrophy is a painful, disabling disorder for which
      no treatment with proven effect is available. We performed a randomized trial in
      a 2 to 1 ratio of patients, in which 36 patients were treated with spinal cord
      stimulation and physical therapy (SCS+PT), and 18 patients received solely PT.
      Twenty-four SCS+PT patients were given a permanent spinal cord stimulation system
      after successful test stimulation; the remaining 12 patients received no
      permanent system. We assessed pain intensity, global perceived effect, functional
      status, and health-related quality of life. Patients were examined before
      randomization, before implantation, and also at 1, 3, 6, 12, and 24 months
      thereafter. At 2 years, three patients were excluded from the analysis. The
      intention-to-treat analysis showed improvements in the SCS+PT group concerning
      pain intensity (-2.1 vs 0.0 cm; p < 0.001) and global perceived effect (43% vs 6%
      "much improved"; p = 0.001). There was no clinically important improvement of
      functional status. Health-related quality of life improved only in the group
      receiving spinal cord stimulation. After careful selection and successful test
      stimulation, spinal cord stimulation results in a long-term pain reduction and
      health-related quality of life improvement in chronic reflex sympathetic
      dystrophy.

PMID- 14705108
TI  - Defeating migraine pain with triptans: a race against the development of
      cutaneous allodynia.
AB  - For many migraine patients, triptan therapy provides complete pain relief in some
      attacks but not in others. Here, we tested whether the success of triptan therapy
      is hindered in the presence of cutaneous allodynia (pain resulting from a
      nonnoxious stimulus to normal skin), a phenomenon we previously described develop
      gradually during the course of the migraine attack in more than 70% of patients.
      We studied migraine patients repeatedly on three visits to the clinic: in the
      absence of migraine (baseline), within the first hour of one attack, or at 4
      hours from onset of another attack. Presence or absence of allodynia was
      determined based on differences between migraine and baseline pain thresholds to
      mechanical and thermal stimulation of periorbital skin. In 31 patients, we
      studied 34 migraine attacks that were associated with allodynia at the time of
      triptan treatment and 27 attacks that were not. Within 2 hours of triptan
      treatment, patients were rendered pain-free in 5 of 34 (15%) of allodynic attacks
      versus 25 of 27 (93%) of nonallodynic attacks. Treating migraine attacks 1 hour
      (early) or 4 hours (late) after the onset of pain was equally ineffective in
      inducing a pain-free state in the presence of allodynia, and equally effective in
      the absence of allodynia. For patients susceptible to allodynia during the
      attack, triptan therapy was by far more likely to provide complete pain relief if
      administered before rather than after the establishment of cutaneous allodynia.
      Patients who never developed allodynia were highly likely to be rendered pain
      free by triptan therapy anytime after the onset of pain. We conclude that the
      probability of consistent pain-free outcome increases drastically if triptan
      therapy is vigilantly timed to precede any signs of cutaneous allodynia.

PMID- 14705109
TI  - Analgesic triptan action in an animal model of intracranial pain: a race against
      the development of central sensitization.
AB  - We have shown that the development of cutaneous allodynia (exaggerated skin
      sensitivity) during migraine is detrimental to the anti-migraine action of the
      5HT(IB/ID) receptor agonists known is triptans. Because cutaneous allodynia is a
      manifestation of sensitization of central trigeminovascular neurons, we examined
      whether triptan treatment can intercept such sensitization before its initiation
      or after its establishment in our rat model for cutaneous allodynia induced by
      intracranial pain. Single-unit recordings were obtained from spinal trigeminal
      neurons that proved to received convergent inputs from the dura and facial skin.
      The effects of sumatriptan (300 microg/kg i.v.) on central sensitization induced
      by topical application of inflammatory soup (IS) on the dura were determined when
      the drug was administered either 2 h after IS (late intervention) or at the same
      time as IS (early intervention). Late sumatriptan intervention counteracted two
      aspects of central sensitization: dural receptive fields, which initially
      expanded by IS, shrunk back after treatment; neuronal response threshold to dural
      indentation, which initially decreased after IS, increased after sumatriptan. On
      the other hand, late sumatriptan intervention did not reverse other aspects of
      central sensitization: spontaneous firing rate and neuronal response magnitude to
      skin brushing which initially increased after IS, remained elevated after
      sumatriptan; response threshold to heating of the skin, which initially dropped
      after IS, remained low after sumatriptan. Early sumatriptan intervention
      effectively blocked the development of all aspects of central sensitization
      expected to be induced 2 h after IS application: dural receptive fields did not
      expand; neuronal response threshold to dural indentation and skin stimulation did
      not decrease; spontaneous firing rate did not increase. The early treatment
      results suggest that triptan action provides a powerful means of preventing the
      initiation of central sensitization triggered by chemical stimulation of
      meningeal nociceptors. The late treatment results suggest that triptan action is
      insufficient to counteract an already established central sensitization. Thus,
      triptan action appears to be exerted directly on peripheral rather than central
      trigeminovascular neurons.

PMID- 14705110
TI  - Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple
      sclerosis with hypothalamic lesions.
AB  - In this postmortem study, we investigated the relationship between multiple
      sclerosis (MS) lesions in the hypothalamus and the state of activity of
      corticotropin-releasing hormone (CRH)-producing neurons that control the
      hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions
      was found in the hypothalamus, of which more than 50% was active, that is,
      contained activated macrophages. MS patients have increased numbers of CRH
      immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of
      chronic activation of CRH neurons and increased CRH mRNA expression. Active MS
      lesions correlated with a low number of hyperactive CRH/VP neurons. High human
      leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and
      microglial activation, correlated with low CRH mRNA expression. The nearer the
      HLA expression was situated to the CRH neurons, the stronger the inhibiting
      effect, suggesting that activated microglial cells or macrophages suppress these
      neurons. The more active MS lesions were present in the hypothalamus, the shorter
      was the disease duration until the moment of death, indicating an unfavorable
      course of the disease. Thus, MS patients have a chronically activated CRH system,
      but, in the subgroup of patients with active MS lesions in the hypothalamus, this
      activation is impaired and the disease course is worse.

PMID- 14705111
TI  - Multiple sclerosis: cytokine receptors on oligodendrocytes predict innate
      regulation.
AB  - Multiple sclerosis (MS) is an immune-mediated demyelinating condition in which
      numerous soluble mediators have been implicated. We have extended the repertoire
      of cytokines studied in MS tissue by examining interleukin (IL-4), IL-6, IL-10,
      IL-12, IL-18, interferon (IFNgamma), and their receptors and have compared
      patterns with those seen in normal subjects and other neurological diseases
      (OND). Expression was evaluated by immunocytochemistry and Western blots.
      Remarkably, oligodendrocytes expressed all the cytokine receptors examined,
      particularly Th2-type, constitutively in normal subjects and upregulated in
      disease. Microglial cells also expressed cytokine receptors at similar levels.
      Cytokine expression was invariably a feature of microglial cells, except for IL
      10, which was exclusively astrocytic. Oligodendrocytes did not display cytokines,
      except for low levels of IL-18. Although no pattern was specific for MS, most
      molecules were upregulated in MS and OND. Downstream JAK/STAT molecules were
      correspondingly upregulated. Cytokine receptors on oligodendrocytes (and
      microglia), and their corresponding ligands on microglia (and astrocytes), may
      implicate paracrine/autocrine regulation and may bespeak innate immunity in the
      central nervous system.

PMID- 14705112
TI  - De novo mutations in the mitochondrial ND3 gene as a cause of infantile
      mitochondrial encephalopathy and complex I deficiency.
AB  - Both nuclear and mitochondrial DNA mutations can cause energy generation
      disorders. Respiratory chain complex I deficiency is the most common energy
      generation disorder and a frequent cause of infantile mitochondrial
      encephalopathies such as Leigh's disease and lethal infantile mitochondrial
      disease. Most such cases have been assumed to be caused by nuclear gene defects,
      but recently an increasing number have been shown to be caused by mutations in
      the mitochondrially encoded complex I subunit genes ND4, ND5, and ND6. We report
      the first four cases of infantile mitochondrial encephalopathies caused by
      mutations in the ND3 subunit gene. Three unrelated children have the same novel
      heteroplasmic mutation (T10158C), only the second mutation reported in ND3, and
      one has the previously identified T10191C mutation. Both mutations cause
      disproportionately greater reductions in enzyme activity than in the amount of
      fully assembled complex I, suggesting the ND3 subunit plays an unknown but
      important role in electron transport, proton pumping, or ubiquinone binding.
      Three cases appear to have a de novo mutation, with no mutation detected in
      maternal relatives. Mitochondrial DNA disease may be considerably more prevalent
      in the pediatric population than currently predicted and should be considered in
      patients with infantile mitochondrial encephalopathies and complex I deficiency.

PMID- 14705113
TI  - Multiple sclerosis in US veterans of the Vietnam era and later military service:
      race, sex, and geography.
AB  - We identified 5345 cases of multiple sclerosis (MS) among US veterans who first
      entered military service between 1960 and 1994, and who were "service-connected"
      for MS by the Department of Veterans Affairs (VA). Two controls per case were
      matched on age, date of service entry, and branch of service. Available for
      service and VA files were demographic and military data for 4951 cases and 9378
      controls. Versus white men, relative risk of MS was significantly higher for all
      women, at 2.99 for whites, 2.86 for blacks, and 3.51 for those of other races.
      This was a significant increase from our prior series of veterans of World War II
      and the Korean Conflict, where white women had a relative risk of 1.79. Risk for
      black men was higher now (0.67 vs 0.44), while other men remained low (0.30 vs
      0.22). Residence at service entry in the northern tier of states had a relative
      risk of 2.02 versus the southern tier, which was significantly less than the 2.64
      for the earlier series. Residence by individual state at birth and service entry
      for white men further supported this decreasing geographic differential. Such
      marked changes in geography, sex, and race in such a short interval strongly
      imply a primary environmental factor in the cause or precipitation of this
      disease.

PMID- 14705114
TI  - Identification of amino-terminally cleaved tau fragments that distinguish
      progressive supranuclear palsy from corticobasal degeneration.
AB  - Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are
      neurodegenerative diseases that are characterized by intracytoplasmic aggregates
      of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP
      and CBD have distinctive pathological features, no biochemical difference in
      aggregated tau has been identified. In this study, we examined the brains of
      eight patients with PSP, six patients with CBD, and one atypical case with
      pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble
      brain extracts, a 33kDa band predominated in the low molecular weight tau
      fragments in PSP, whereas two closely related bands of approximately 37kDa
      predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band
      and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that
      the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with
      different amino termini. These results suggest that, despite the identical
      composition of tau isoforms, different proteolytic processing of abnormal tau
      takes place in these two diseases. Such a biochemical divergence may be related
      to the neuropathological features of these diseases.

PMID- 14705115
TI  - Metabolic and neuropsychological phenotype in women heterozygous for ornithine
      transcarbamylase deficiency.
AB  - We compared neurocognitive indices with clinical status, mutation analysis, and
      urea synthetic capacity in 19 women heterozygous for ornithine transcarbamylase
      deficiency. Although as a group, these women had average IQ scores, they
      displayed a specific neuropsychological phenotype with significant strengths in
      verbal intelligence, verbal learning, verbal memory, and reading, and significant
      weaknesses in fine motor dexterity/speed and nonsignificant weaknesses in
      nonverbal intelligence, visual memory, attention/executive skills, and math. This
      suggests selective vulnerability of white matter and better preservation of gray
      matter. When the group was divided into symptomatic and asymptomatic subgroups,
      based on either clinical history or residual urea synthetic capacity, the
      asymptomatic subgroup outperformed the symptomatic subgroup on all tested domains
      of neuropsychological functioning. Furthermore, the amount of residual urea
      synthetic capacity was predictive of several end point cognitive measures. There
      was no correlation between neonatal versus late-onset mutation or between normal
      or abnormal allopurinol challenge and neuropsychological outcome. In sum, we
      identified a specific metabolic and neurocognitive phenotype in women
      heterozygous for ornithine transcarbamylase deficiency. The findings support the
      importance of maintaining meticulous metabolic control in children with urea
      cycle disorders, because even mildly symptomatic subjects demonstrate cognitive
      deficits.

PMID- 14705116
TI  - The amygdala and sexual drive: insights from temporal lobe epilepsy surgery.
AB  - The aim of this study was to explore the relationship between the amygdala and
      human sex drive. We compared amygdalar volume in groups of patients with or
      without sexual changes after temporal lobe resection and in age-matched
      neurologically normal subjects. Forty-five patients with intractable temporal
      lobe epilepsy who underwent surgical resection in the Comprehensive Epilepsy
      Program at the Austin and Repatriation Medical Centre completed a semistructured
      interview and questionnaire relating to sexual outcome after surgery. Volumetric
      analyses of both amygdalae were conducted on the patients' preoperative T(1)
      weighted magnetic resonance imaging scans and those of 46 neurologically normal
      controls. Patients who reported a postoperative sexual increase had a
      significantly larger amygdalar volume contralateral to the site of their
      resective surgery than patients with a sexual decrease or no change than control
      subjects. There was a significant positive relationship between contralateral
      amygdalar volume and the maximum degree of sexual change. We have demonstrated a
      relationship between contralateral amygdalar volume and sexual outcome in
      patients undergoing temporal lobe resection. This finding provides evidence for
      an important role of the amygdala in regulating human sexual behavior. A larger
      contralateral amygdala may contribute to the expression of increased or improved
      sexuality after temporal lobe resection.

PMID- 14705117
TI  - Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p.
AB  - Autosomal dominant cerebellar ataxias constitute one of the most clinically,
      neuropathologically, and genetically heterogeneous groups of neurodegenerative
      disorders. Approximately 50 to 80% of the families carry mutations in genes known
      to be implicated in spinocerebellar ataxias (SCAs). Numerous loci (SCAn) also
      have been mapped, often in single families, but the responsible genes have not
      yet been identified. This suggests further genetic heterogeneity. We have
      ascertained 18 subjects from a large French family in which cerebellar ataxia and
      prominent sensory neuropathy segregated as a dominant trait. Intrafamilial
      variability was high regarding age at onset (17 months to 39 years), severity,
      and the clinical picture that ranged from pure sensory neuropathy with little
      cerebellar involvement to a Friedreich's ataxia-like phenotype. After excluding
      known genes/loci responsible for SCA and hereditary sensory neuropathies, we
      detected linkage with chromosome 2p markers in a genomewide screen. We designated
      this new locus SCA25 after testing of 16 additional markers. Maximum two-point
      logarithm of odds scores of 3.15 and 3.10 were obtained at D2S2378 and D2S2734,
      respectively. Haplotype analysis defined a critical 12.6cM region of 15Mb between
      D2S2174 and D2S2736. No linkage to this locus was found in four other families.
      This interval contains several genes that could be responsible for the disease.
      One of these genes, CRIPT, encodes a postsynaptic protein, but no mutations were
      found by direct sequencing, excluding its responsibility in the disease. CAG
      repeat expansions often are involved in SCA pathogenesis, but no pathological
      expansions were found at the protein or at the DNA level using the 1C2 antibody
      and the repeat expansion detection method, respectively. The gene responsible for
      SCA25 remains to be identified.

PMID- 14705118
TI  - Early magnetic resonance imaging findings in patients receiving tissue
      plasminogen activator predict outcome: Insights into the pathophysiology of acute
      stroke in the thrombolysis era.
AB  - We measured ischemic brain changes with diffusion and perfusion MRI in 42
      ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5
      hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The
      median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables
      (change in perfusion and/or diffusion weighted lesion volume) were compared
      between those with excellent outcome defined as 3-month modified Rankin score
      (mRS) of 0 to 1 and those with incomplete recovery (mRS >1). In multivariate
      logististic regression analysis, the most powerful independent predictor for
      excellent outcome was improved brain perfusion: hypoperfusion volume on mean
      transit time (MTT) map decrease >30% from baseline to 2-hour post tPA scan
      (p=0.009; odds ratio [95% confidence interval], 20.7 [2.1-203.9]). Except for age
      < 70 years, no other baseline clinical or imaging variable was an independent
      predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours
      after tPA as an early marker of long-term clinical benefit of thrombolytic
      therapy.

PMID- 14705119
TI  - DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia.
AB  - Two novel mutations recently have been identified in the DJ-1 gene that cause a
      new form of autosomal recessive, early-onset parkinsonism. Because the
      pathological role of this protein is unknown, we examined the issue here and
      report the colocalization of DJ-1 protein within a subset of pathological tau
      inclusions in a diverse group of neurodegenerative disorders known as
      tauopathies. Our study extends the view that different neurodegenerative diseases
      may have similar pathological mechanisms, and that these processes likely include
      DJ-1.

PMID- 14705120
TI  - Effect of subthalamic deep brain stimulation on the function of the urinary
      bladder.
AB  - Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from
      Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic
      deep brain stimulation has a significant and urodynamically recordable effect
      leading to a normalization of pathologically increased bladder sensibility.

PMID- 14705121
TI  - Creutzfeldt-Jakob disease and inclusion body myositis: abundant disease
      associated prion protein in muscle.
AB  - Pathologicalprion protein (PrP(Sc)) is the hallmark of prion diseases affecting
      primarily the central nervous system. Using immunohistochemistry, paraffin
      embedded tissue blot, and Western blot, we demonstrated abundant PrP(Sc) in the
      muscle of a patient with sporadic Creutzfeldt-Jakob disease and inclusion body
      myositis. Extraneural PrP(C)-PrP(Sc) conversion in Creutzfeldt-Jakob disease
      appears to become prominent when PrP(C) is abundantly available as substrate, as
      in inclusion body myositis muscle.

PMID- 14705122
TI  - Brain dopamine-stimulated adenylyl cyclase activity in Parkinson's disease,
      multiple system atrophy, and progressive supranuclear palsy.
AB  - The dopamine D(1) receptor is considered to participate in levodopa's
      antiparkinsonian action and levodopa-induced dyskinesias. We examined the
      functional status of the D(1) receptor in brain of patients with Parkinson's
      disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy
      (PSP). Dopamine-stimulated adenylyl cyclase activity was significantly increased
      in putamen (+43%) and frontal cortex (+52%) in PD, normal in PSP, but decreased
      by 47% in putamen in MSA. The supersensitive dopamine D(1) receptors in both
      striatum and cerebral cortex in PD might compensate for dopamine deficiency, but
      could also contribute to long-term complications of levodopa therapy.

PMID- 14705123
TI  - Complex phenotypes in an Indian family with homozygous SCA2 mutations.
AB  - We describe a consanguineous Indian family having spinocerebellar ataxia type 2
      (SCA2) expansions with complex phenotypes (early-onset, dopa-responsive
      parkinsonism, ataxia and retinitis pigmentosa). The two probands having
      homozygous SCA2 mutations presenting with early-onset dopa-responsive
      parkinsonism without ataxia develop dyskinesias within a year of starting
      levodopa. Their siblings, heterozygous for SCA2 mutations, had retinitis
      pigmentosa with or without ataxia. Approximately 38% of family members with SCA2
      mutations were asymptomatic.

PMID- 14705124
TI  - Chromosomal translocation t(18;21)(q23;q22.1) indicates novel susceptibility loci
      for frontotemporal dementia with ALS.
AB  - A chromosomal translocation t(18;21)(q23;q22) is reported in a patient with
      frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We exclude
      the physical involvement and silencing of the ALS-linked gene for copper/zinc
      superoxide dismutase (SOD1) on chromosome 21q22.1. The breakpoints are assigned
      to sequences flanked by the markers ATA1H06, D18S462, D21S1915, and D21S1898.
      These critical regions may contain susceptibility loci for FTD associated with
      ALS.

PMID- 14705125
TI  - Tactile awareness and limb position in neglect: functional magnetic resonance
      imaging.
AB  - We studied a patient with right parietal damage for whom tactile stimuli on the
      right/ipsilesional hand (projecting to the intact left hemisphere) were
      extinguished from awareness during double simultaneous stimulation, when his
      right hand was positioned in the left/contralesional space. This demonstrates the
      role of an egocentric spatial reference frame in attention that can determine
      awareness of stimuli despite intact sensory pathways. Using functional magnetic
      resonance imaging to elucidate the neural correlates of such perceptual
      extinction, we found that limb position modulated neural responses to tactile
      stimuli at early cortical stages (SI) in the intact hemisphere. Activity in
      bilateral middle frontal gyri also was modulated by limb position and may
      contribute to integrate sensory inputs into a supramodal, egocentric
      representation of space.

PMID- 14705126
TI  - Does alcohol cancel static vestibular compensation?

PMID- 14705128
TI  - The R98Q variation in DJ-1 represents a rare polymorphism.

PMID- 14705129
TI  - Calpain 3 deficiency in Quail Eater's disease.

PMID- 14705130
TI  - Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency.

PMID- 14705136
TI  - Neuroprotective functions of prion protein.
AB  - The normal function of prion protein (PrP) is usually disregarded at the expense
      of the more fascinating role of PrP in transmissible prion diseases. However, the
      normal PrP may play an important role in cellular function in the central nervous
      system, since PrP is highly expressed in neurons and motifs in the sequence of
      PrP are conserved in evolution. The finding that prion null mice do not have a
      significant overt phenotype suggests that the normal function of PrP is of minor
      importance. However, the absence of PrP in cells or in vivo contributes to an
      increased susceptibility to oxidative stress or apoptosis-inducing insults. An
      alternative explanation is that the PrP normal function is so important that it
      is redundant. Probing into the characteristics of PrP has revealed a number of
      features that could mediate important cellular functions. The neuroprotective
      actions so far identified with PrP are initiated through cell surface signaling,
      antioxidant activity, or anti-Bax function. Here, we review the characteristics
      of the PrP and the evidence that PrP protects against neurodegeneration and
      neuronal cell death.

PMID- 14705137
TI  - Residues 17-20 and 30-35 of beta-amyloid play critical roles in aggregation.
AB  - We examined the effects of co-incubating nine different Abeta peptide fragments
      with full-length Abeta1-40 (Abeta40) on protein aggregation. Six fragments
      enhanced aggregation of Abeta40 (Abeta1-28, 12-28, 17-28, 10-20, 25-35 and 17
      40), while three others did not (Abeta1-11, 1-16, and 20-29). All of the peptides
      that enhanced aggregation contained either residues 17-20 or 30-35, indicating
      the importance of these regions for promoting aggregation of full-length Abeta.
      Abeta25-35 in particular increased both the rate and extent of aggregation of
      Abeta40 considerably as indicated by fluorescence staining. Atomic force
      microscope imaging (AFM) indicates the increase in fluorescence staining with
      Abeta25-35 is primarily due to increased formation of oligomers and protofibrils
      rather than formation of large amyloid fibrils. AFM images of Abeta25-35 when
      incubated alone also indicate formation of aggregates and long thin filaments.
      The increase in formation of the small toxic oligomeric morphology of Abeta40,
      along with formation of Abeta25-35 oligomers and thin filaments, represent two
      different potential pathways for Abeta25-35 toxicity. The critical roles of
      residues 17-20 and 30-35 of Abeta provide further insight into mechanism that
      underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest
      targets for the design of beta-sheet breakers to modulate the aggregation and
      inhibit toxicity of full-length Abeta.

PMID- 14705138
TI  - Water maze learning and forebrain mRNA expression of the neural cell adhesion
      molecule L1.
AB  - L1 and NCAM, two cell adhesion molecules of the immunoglobulin superfamily, have
      been implicated in the formation of neural circuits, synaptic plasticity, and
      cognitive function. In this study, we sought to investigate whether differences
      in the steady-state levels of L1 and NCAM expression in specific brain regions
      could account for individual differences in learning abilities. Using adult male
      Wistar rats, we evaluated mRNA levels of L1, NCAM, and the NCAM180 isoform in
      different brain regions (hippocampus, thalamus, striatum, prefrontal and frontal
      cortices) immediately after submitting rats to a massed training protocol in the
      water maze. The results showed that untrained and trained rats exhibited similar
      levels of mRNA for these molecules, which supports the view that training did not
      influence their immediate level of expression. However, in most of the brain
      regions we investigated (with the exception of prefrontal and frontal cortices),
      L1 mRNA levels were positively correlated with the latency to find the hidden
      platform in the water maze task and with posttraining plasma corticosterone
      levels. However, no correlations were observed for total NCAM or NCAM180 mRNA in
      the brain regions examined in this study. Given that animals with a slower
      spatial acquisition curve exhibited more anxiety-like responses, including
      thigmotactic behavior in the water maze and increased corticosterone levels, and
      that recent genetic studies indicate a role for L1 in anxiety, the current
      findings suggest a relationship among L1, anxiety, and cognitive processes.

PMID- 14705139
TI  - Expression and functional properties of group I metabotropic glutamate receptors
      in bovine chromaffin cells.
AB  - We demonstrate the presence and functional properties of Group I metabotropic
      glutamate receptors (mGluRs) expressed in chromaffin cells. Immunocytochemical
      techniques revealed that two mGluR subtypes (mGluR1alpha and mGluR5) are
      expressed in chromaffin cells, located in both the cytoplasmic membrane and the
      cytosol surrounding the nucleus. These mGluRs are functionally active on
      catecholamine (CA) secretion in chromaffin cells because both (1S, 3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and the specific agonist of
      Group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), were able to stimulate the
      release of CAs (adrenaline and noradrenaline) in a dose-response manner. These
      effects were specifically reversed by L-(+)-2-amino-3-phosphonopropionic acid (L
      AP3), a selective antagonist of the Group I metabotropic glutamate receptors. t
      ACPD induced an increase in CA secretion in both the presence and absence of
      extracellular calcium, the former effect being accompanied by cell membrane
      depolarization. Noradrenaline (NA) release was higher in the presence of
      extracellular calcium than in its absence, whereas adrenaline release was of the
      same order under both conditions. These results indicate that different subtypes
      of Group I mGluRs are present in noradrenergic and adrenergic cells. Fluorescence
      imaging techniques in single cells showed different t-ACPD-induced increases in
      intracellular calcium in different chromaffin cells: in chromaffin cells, 67%
      expressed functional metabotropic glutamate receptors and with nicotinic
      receptors, whereas the remaining 33% expressed only nicotinic receptors. In the
      absence of external calcium, only about 25% of cells responded to t-ACPD
      increased intracellular calcium by increasing inositol 1,4,5-trisphosphate
      (IP(3)) concentration and subsequent calcium mobilization from intracellular
      stores, whereas the remaining 75% increased intracellular calcium by promoting
      Ca(2+) influx from the extracellular medium through L- and N- but not P/Q voltage
      dependent calcium channels.

PMID- 14705140
TI  - Subpopulations of rat dorsal root ganglion neurons express active vesicular
      acetylcholine transporter.
AB  - The vesicular acetylcholine transporter (VAChT) is a transmembrane protein
      required, in cholinergic neurons, for selective storage of acetylcholine into
      synaptic vesicles. Although dorsal root ganglion (DRG) neurons utilize
      neuropeptides and amino acids for neurotransmission, we have previously
      demonstrated the presence of a cholinergic system. To investigate whether, in
      sensory neurons, the vesicular accumulation of acetylcholine relies on the same
      mechanisms active in classical cholinergic neurons, we investigated VAChT
      presence, subcellular distribution, and activity. RT-PCR and Western blot
      analysis demonstrated the presence of VAChT mRNA and protein product in DRG
      neurons and in the striatum and cortex, used as positive controls. Moreover, in
      situ hybridization and immunocytochemistry showed VAChT staining located mainly
      in the medium/large-sized subpopulation of the sensory neurons. A few small
      neurons were also faintly labeled by immunocytochemistry. In the electron
      microscope, immunolabeling was associated with vesicle-like elements distributed
      in the neuronal cytoplasm and in both myelinated and unmyelinated intraganglionic
      nerve fibers. Finally, [(3)H]acetylcholine active transport, evaluated either in
      the presence or in the absence of ATP, also demonstrated that, as previously
      reported, the uptake of acetylcholine by VAChT is ATP dependent. This study
      suggests that DRG neurons not only are able to synthesize and degrade ACh and to
      convey cholinergic stimuli but also are capable of accumulating and, possibly,
      releasing acetylcholine by the same mechanism used by the better known
      cholinergic neurons.

PMID- 14705141
TI  - Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and
      terminal degeneration in normal and TNF-transgenic mice.
AB  - The inflammatory cytokine tumour necrosis factor (TNF) can both induce
      oligodendrocyte and myelin pathology and promote proliferation of oligodendrocyte
      progenitor cells and remyelination. We have compared the response of the
      oligodendrocyte lineage to anterograde axonal (Wallerian) and terminal
      degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus
      in TNF-transgenic mice with the response in genetically normal mice.
      Transectioning of the entorhino-dentate perforant path axonal projection
      increased hippocampal TNF mRNA expression in both types of mice, but to
      significantly larger levels in the TNF-transgenics. At 5 days after axonal
      transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA
      expression in the denervated dentate gyrus in TNF-transgenic mice had increased
      to the same extent as in nontransgenic littermates. At this time, transgenics
      showed a tendency towards a greater increase in the number of juxtaposed,
      potentially proliferating oligodendrocytes. Noteworthy, at day 5 we also observed
      upregulation of MBP mRNA expression in adjacent hippocampal subregions with
      lesion-induced axonal sprouting, which were devoid of axonal degeneration,
      raising the possibility that sprouting axons provide trophic stimuli to the
      oligodendrocyte lineage. Twenty-eight days after lesioning, oligodendrocyte
      numbers and MBP mRNA expression were reduced to near normal levels. However,
      oligodendrocyte densities in the TNF-transgenic mice were significantly lower
      than in nontransgenics. We conclude that the early response of the
      oligodendrocyte lineage to axonal lesioning and lesion-induced axonal sprouting
      appears unaffected by the supranormal TNF levels in the TNF-transgenic mice. TNF
      may, however, have long-term inhibitory effects on the oligodendrocyte response
      to axonal lesioning.

PMID- 14705142
TI  - High-level expression of Dok-1 in neurons of the primate prefrontal cortex and
      hippocampus.
AB  - The docking protein p62Dok-1 (Dok-1) has a central role in cell signaling
      mediated by a wide range of protein tyrosine kinases, including intrinsic
      membrane kinases, such as the insulin-like growth factor-1 (IGF-1) receptor. To
      elucidate potential IGF signaling mechanisms, we used DNA array technology to
      investigate novel kinase targets expressed in the primate dorsolateral prefrontal
      cortex (DLPFC). Dok-1 transcripts were among the most abundant found in this
      structure. Because Dok-1 expression has not been characterized in brain, we
      evaluated its expression pattern using immunoblotting, in situ hybridization, and
      immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal
      formation. Dok-1 antibodies identified a 62-kDa band in lysates from the DLPFC,
      consistent with the known size for Dok-1. In situ hybridization showed that Dok-1
      mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of
      the hippocampal formation. Immunohistochemical analysis showed Dok-1
      immunoreactivity concentrated in pyramidal neurons of cortical layers IV-V and
      throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok-1
      expression was also identified in endothelial cells of cerebral blood vessels.
      These expression patterns are very similar to those of the IGF-1 receptor and
      suggest that Dok-1 could be among the downstream targets of IGF signaling in
      areas of the primate brain involved in learning and memory.

PMID- 14705143
TI  - Differential effects of zinc on glutamatergic and GABAergic neurotransmitter
      systems in the hippocampus.
AB  - Approximately 10% of total zinc in the brain exists in synaptic vesicles of
      glutamatergic neurons; however, the function of vesicular zinc is poorly
      understood. The presynaptic action of zinc against excitatory and inhibitory
      neurotransmission was studied in rat hippocampus using in vivo microdialysis.
      When the hippocampal CA3 region was perfused with 10-300 microM ZnCl(2), the
      level of glutamate in the perfusate was decreased, whereas the level of gamma
      aminobutyric acid (GABA) was increased. Chelation of endogenous zinc with CaEDTA
      increased the glutamate level in the perfusate but decreased the GABA level,
      suggesting that zinc released into the synaptic cleft acts differentially on
      glutamatergic and GABAergic neurons in the CA3 region. The increase of GABA level
      by zinc was antagonized by 2,3-dioxo-6-nitro-1,2.3,4
      tetrahydrobenzo(f)quinoxaline-7-sulphonamide (NBQX), an antagonist of alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors, but not
      affected by MK801, an antagonist of N-methyl-D-aspartate (NMDA) receptors, and
      verapamil, a blocker of voltage-dependent calcium channels. The present study
      suggests that zinc enhances GABA release via potentiation of AMPA/kainate
      receptors in the CA3 region, followed by a decrease in presynaptic glutamate
      release in the same region. Zinc seems to be an inhibitory neuromodulator of
      glutamate release.

PMID- 14705144
TI  - Functional alterations in immature cultured rat hippocampal neurons after
      sustained exposure to static magnetic fields.
AB  - In cultured rat hippocampal neurons, gradual increases were seen in the
      expression of microtubule-associated protein-2 (MAP-2), neuronal nuclei (NeuN)
      and growth-associated protein-43 (GAP-43), in proportion to increased duration,
      up to 9 days in vitro (DIV). Sustained exposure to static magnetic fields at 100
      mT for up to 9 DIV significantly decreased expression of MAP-2 and NeuN in
      cultured rat hippocampal neurons without markedly affecting GAP-43 expression.
      Although a significant increase was seen in the expression of glial fibrillary
      acidic protein (GFAP) in hippocampal neuronal preparations cultured for 6-9 DIV
      under sustained magnetism, GFAP and proliferating cell nuclear antigen expression
      were not affected markedly in cultured astrocytes prepared from rat hippocampus
      and neocortex, irrespective of cellular maturity. No significant alteration was
      seen in cell survivability of hippocampal neurons or astrocytes cultured under
      sustained magnetism. In hippocampal neurons cultured for 3 DIV under sustained
      magnetism, marked mRNA expression was seen for N-methyl-D-aspartate (NMDA)
      receptor subunits, NR1, NR2A-2C, NR2D, and NR3A. In addition, significant
      potentiation of the ability of NMDA to increase intracellular free Ca(2+) ions
      was observed. Differential display analysis revealed a significant decrease in
      mRNA expression for the transcription factor ALF1 in response to sustained
      magnetism for 3 DIV. These results suggest that sustained exposure to static
      magnetic fields may affect cellular functionality and maturity in immature
      cultured rat hippocampal neurons through modulation of expression of particular
      NMDA receptor subunits.

PMID- 14705145
TI  - Retinoic acid-induced neuritogenesis of human neuroblastoma SH-SY5Y cells is ERK
      independent and PKC dependent.
AB  - Retinoic acid (RA), an active metabolite of vitamin A, is a natural morphogen
      involved in development and differentiation of the nervous system. To elucidate
      signaling mechanisms involved in RA-induced neuritogenesis, we used human
      neuroblastoma SH-SY5Y cells, an established in vitro model for studying RA
      action, to examine the role of extracellular signal-regulated kinase (ERK) 1 and
      2 in RA-induced neuritogenesis and cell survival. From immunoblotting
      experiments, we observed that RA induced delayed but persistent ERK1 and ERK2
      phosphorylation (until 96 hr) that was reduced significantly by the specific
      mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126. For the
      subsequent studies we chose 24 hr as the reference time. Inhibition of ERK
      activation did not affect RA-induced neuritogenesis (percentage of neurite
      bearing cells and neurite length) but significantly reduced cell survival. In
      addition, we analyzed the signaling pathway that mediates ERK activation. Our
      results suggest that RA-induced ERK phosphorylation does not follow the classic
      Raf kinase-dependent pathway. Protein kinase C (PKC) and phosphatidylinositol 3
      kinase (PI 3-K) are possible alternative kinases involved in the ERK signaling
      pathway. In fact, in the presence of the specific PKC inhibitor GF 109203X, or
      the specific PI 3-K inhibitor wortmannin, we observed a significant dose
      dependent reduction in ERK phosphorylation. RA-induced neuritogenesis and cell
      survival were reduced by GF 109203X in a concentration-dependent manner. These
      results suggest that rather than ERK1 and ERK2, it is PKC that plays an important
      role during early phases of RA-induced neuritogenesis.

PMID- 14705146
TI  - Repetitive transcranial magnetic stimulation improves open field locomotor
      recovery after low but not high thoracic spinal cord compression-injury in adult
      rats.
AB  - Electromagnetic fields are able to promote axonal regeneration in vitro and in
      vivo. Repetitive transcranial magnetic stimulation (rTMS) is used routinely in
      neuropsychiatric conditions and as an atraumatic method to activate descending
      motor pathways. After spinal cord injury, these pathways are disconnected from
      the spinal locomotor generator, resulting in most of the functional deficit. We
      have applied daily 10 Hz rTMS for 8 weeks immediately after an incomplete high
      (T4-5; n = 5) or low (T10-11; n = 6) thoracic closed spinal cord compression
      injury in adult rats, using 6 high- and 6 low-lesioned non-stimulated animals as
      controls. Functional recovery of hindlimbs was assessed using the BBB locomotor
      rating scale. In the control group, the BBB score was significantly better from
      the 7th week post-injury in animals lesioned at T4-5 compared to those lesioned
      at T10-11. rTMS significantly improved locomotor recovery in T10-11-injured rats,
      but not in rats with a high thoracic injury. In rTMS-treated rats, there was
      significant positive correlation between final BBB score and grey matter density
      of serotonergic fibres in the spinal segment just caudal to the lesion. We
      propose that low thoracic lesions produce a greater functional deficit because
      they interfere with the locomotor centre and that rTMS is beneficial in such
      lesions because it activates this central pattern generator, presumably via
      descending serotonin pathways. The benefits of rTMS shown here suggest strongly
      that this non-invasive intervention strategy merits consideration for clinical
      trials in human paraplegics with low spinal cord lesions.

PMID- 14705147
TI  - Prevention of gliotic scar formation by NeuroGel allows partial endogenous repair
      of transected cat spinal cord.
AB  - Spinal cords of adult cats were transected and subsequently reconnected with the
      biocompatible porous poly (N-[2-hydroxypropyl] methacrylamide) hydrogel,
      NeuroGel. Tissue repair was examined at various time points from 6-21 months post
      reconstructive surgery. We examined two typical phenomena, astrogliosis and scar
      formation, in spines reconstructed with the gel and compared them to those from
      transected non-reconstructed spines. Confocal examination with double
      immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic
      protein (MBP) showed that the interface formed between the hydrogel and the spine
      stumps did prevent scar formation and only a moderate gliosis was observed. The
      gel implant provided an adequate environment for growth of myelinated fibers and
      we saw angiogenesis within the gel. Electron microscopy showed that regenerating
      axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover,
      the presence of the gel implant lead to a considerable reduction in damage to
      distal caudal portions of the spine as assessed by the presence of more intact
      myelinated fibers and a reduction of myelin degradation. Neurologic assessments
      of hindlimb movement at various times confirmed that spinal cord reconstruction
      was not only structural but also functional. We conclude that NeuroGel lead to
      functional recovery by providing a favorable substrate for regeneration of
      transected spinal cord, reducing glial scar formation and allowing angiogenesis.

PMID- 14705148
TI  - Transient focal ischemia in rat brain differentially regulates mRNA expression of
      protease-activated receptors 1 to 4.
AB  - Degeneration or survival of cerebral tissue after ischemic injury depends on the
      source, intensity, and duration of the insult. In the model of focal ischemia,
      reduced blood flow results in a cascade of pathophysiologic events, including
      inflammation, excitotoxicity, and platelet activation at the site of injury. One
      serine protease that is associated closely with and produced in response to
      central nervous system (CNS) injury is thrombin. Thrombin enters the injury
      cascade in brain either via a compromised blood-brain barrier or possibly from
      endogenous prothrombin. Thrombin mediates its action through the protease
      activated receptor family (PAR-1, -3, and -4). PARs belong to the superfamily of
      G protein-coupled receptors with a 7-transmembrane domain structure and are
      activated by proteolytic cleavage of their N-terminus. We showed that thrombin
      can be neuroprotective or deleterious when present at different concentrations
      before and during oxygen-glucose deprivation, an in vitro model of ischemia. We
      examined the change in mRNA expression levels of PAR-1 to 4 as a result of
      transient focal ischemia in rat brain, induced by microinjection of endothelin
      near the middle cerebral artery. Using semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis, after ischemic insult on the
      ipsilesional side, PAR-1 was found to be downregulated significantly, whereas PAR
      2 mRNA levels decreased only moderately. PAR-3 was upregulated transiently and
      then downregulated, and PAR-4 mRNA levels showed the most striking (2.5-fold)
      increase 12 hr after ischemia, in the injured side. In the contralateral
      hemisphere, mRNA expression was also affected, where decreased mRNA levels were
      observed for PAR-1, -2, and -3, whereas PAR-4 levels were reduced only after 7
      days. Taken together, these data suggest involvement of the thrombin receptors
      PAR-1, PAR-3, and PAR-4 in the pathophysiology of brain ischemia.

PMID- 14705149
TI  - Antioxidant effect of acetylsalicylic and salicylic acid in rat brain slices
      subjected to hypoxia.
AB  - Acetylsalicylic acid (ASA) reduces the incidence of ischemic stroke mainly
      through its antithrombotic action; however, it also has a direct neuroprotective
      effect. The present study was designed to evaluate the effect of ASA on oxidative
      stress and the activity of nitric oxide synthase (NOS) in an in vitro model of
      hypoxia in rat brain slices. Rat brain slices were perfused with nitrogen
      (hypoxia) for a maximum of 120 min, after which we measured lipid peroxidation,
      glutathione levels, glutathione-related enzyme activities, and constitutive
      nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS)
      activities. In brain tissue subjected to hypoxia, ASA reduced oxidative stress
      and iNOS activity (all increased by hypoxia), but only when used at higher
      concentrations. The effects of salicylic acid (SA) were similar but more intense
      than were those of ASA. After oral administration, the effect of SA was much
      greater than that of ASA, and the decrease in cell death with SA was seen much
      more clearly. In view of the greater effect of SA compared to ASA on changes in
      oxidative stress parameters in a model of hypoxia, and higher brain
      concentrations of SA when it is administered alone than when ASA is given
      (undetectable levels), we conclude that SA plays an important role in the
      cytoprotective effect in brain tissue after ASA administration.

PMID- 14705150
TI  - Down-regulation of caveolin-1 in glioma vasculature: modulation by radiotherapy.
AB  - Primary brain tumors, particularly glioblastomas (GB), remain a challenge for
      oncology. An element of the malignant brain tumors' aggressive behavior is the
      fact that GB are among the most densely vascularized tumors. To determine some of
      the molecular regulations occuring at the brain tumor endothelium level during
      tumoral progression would be an asset in understanding brain tumor biology.
      Caveolin-1 is an essential structural constituent of caveolae that has been
      implicated in mitogenic signaling, oncogenesis, and angiogenesis. In this work we
      investigated regulation of caveolin-1 expression in brain endothelial cells (ECs)
      under angiogenic conditions. In vitro, brain EC caveolin-1 is down-regulated by
      angiogenic factors treament and by hypoxia. Coculture of brain ECs with tumoral
      cells induced a similar down-regulation. In addition, activation of the p42/44
      MAP kinase is demonstrated. By using an in vivo brain tumor model, we purified
      ECs from gliomas as well as from normal brain to investigate possible regulation
      of caveolin-1 expression in tumoral brain vasculature. We show that caveolin-1
      expression is strikingly down-regulated in glioma ECs, whereas an increase of
      phosphorylated caveolin-1 is observed. Whole-brain radiation treatment, a
      classical way in which GB is currently being treated, resulted in increased
      caveolin-1 expression in tumor isolated ECs. The level of tumor cells spreading
      around newly formed blood vessels was also elevated. The regulation of caveolin-1
      expression in tumoral ECs may reflect the tumoral vasculature state and
      correlates with angiogenesis kinetics.

PMID- 14705151
TI  - Combining universal and targeted prevention for school-based eating disorder
      programs.
AB  - OBJECTIVE: This study examined a step toward providing a universal prevention
      program to all students while targeting those at risk. METHOD: Seventy-eight 10th
      grade female students were provided an on-line eating disorder prevention program
      and randomized to participate in (1) a higher risk and higher motivated group,
      (2) a lower risk or lower motivated group, or (3) a combined group. RESULTS: The
      students in the first group made significantly fewer negative and more positive
      comments in the on-line group discussion than the higher risk and higher
      motivated participants in the combined group. However, there were no differences
      among groups on outcome measures. DISCUSSION: The results suggest that, because
      it is relatively easy to provide interventions with separate groups, it seems
      appropriate to do so, if for no other reason than to minimize the few very
      negative comments that were posted by students that might have created an adverse
      environment for the higher risk-participants that the intervention specifically
      targets.

PMID- 14705152
TI  - Use of nutritional supplements to increase the efficacy of fluoxetine in the
      treatment of anorexia nervosa.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not
      appear to be effective in ill, malnourished anorexia nervosa (AN) patients.
      However, it may be effective in preventing relapse after weight restoration. The
      purpose of this study was to determine whether nutritional supplements could
      potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty
      six subjects with AN participated in a trial of fluoxetine. In a double-blind,
      placebo-controlled manner, subjects received either nutritional supplements or a
      nutritional placebo. The nutritional supplement included tryptophan (the
      precursor of serotonin), vitamins, minerals, and essential fatty acids believed
      to influence serotonin pathway function. RESULTS: There was no significant
      difference in weight gain between subjects treated with fluoxetine plus
      nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover,
      there were no significant differences between groups on mean changes in anxiety
      or obsessive and compulsive symptoms. DISCUSSION: The results of this study
      suggest that supplement strategies are not a substitute for adequate nutrition
      and are ineffective in increasing the efficacy of fluoxetine in underweight AN
      subjects.

PMID- 14705153
TI  - Clinical trial of sertraline in the treatment of night eating syndrome.
AB  - OBJECTIVE: To test the efficacy of sertraline in the treatment of night eating
      syndrome. METHODS: Seventeen patients meeting criteria for night eating syndrome
      received sertraline in a 12-week open-label, nonblind trial. Outcome was assessed
      by four primary measures, namely, the number of nocturnal awakenings, the number
      of ingestions, total daily caloric intake after the evening meal, and an overall
      rating of change from the Clinical Global Impression of Improvement scale (CGI
      I). RESULTS AND DISCUSSION: An intent-to-treat analysis revealed highly
      significant improvements across all four primary outcome measures for all 17
      subjects. Five subjects achieved full remission of symptoms (CGI-I score of 1 =
      very much improved) and lost a significant amount of weight over the course of
      the study (-4.8 +/- 2.6 kg, p < .05). Sertraline, a selective serotonin reuptake
      inhibitor, may be beneficial in the treatment of night eating syndrome.

PMID- 14705154
TI  - Survey of regional health care providers on selection of treatment for bulimia
      nervosa.
AB  - OBJECTIVE: To determine which treatments clinicians currently recommend for
      patients with bulimia nervosa (BN), to find out if they recommended evidence
      based treatments, and to assess availability and clinician satisfaction with
      treatment options. METHODS: Surveys were sent to 1,263 health care providers in
      Minnesota, Iowa, and Wisconsin who were likely to encounter patients with BN.
      These health care providers comprised all primary care clinicians, physician
      assistants, advanced practice nurses, and all mental health/chemical dependency
      clinicians (MDs, Clinical Nurse Specialist (CNS), social workers, doctoral and
      masters-level therapists, and chemical dependency (CD) counselors) affiliated
      with the Mayo Clinic in Rochester, Minnesota. RESULTS: Evidence-based treatments
      for BN are recommended consistently and are generally perceived to be available,
      at least to practitioners affiliated with a large medical center in the Midwest.
      Clinician satisfaction with treatment options is modest. DISCUSSION: Clinicians
      are recommending evidence-based treatments for BN patients and find them to be
      generally available. Modest satisfaction with available treatments may reflect a
      realistic understanding of treatment options, which need further development.

PMID- 14705155
TI  - Participant recruitment for an anorexia nervosa treatment study.
AB  - OBJECTIVE: To investigate the nature of differing recruitment rates for clinical
      treatment trials for anorexia nervosa and bulimia nervosa. METHODS: Recruitment
      rates from a study recruiting women partially recovered from anorexia nervosa
      were compared with the rates from two studies conducted at the same sites
      recruiting women with bulimia nervosa. RESULTS: At all sites in the anorexia
      study, the total number of contacts per month rose steadily over the first 2
      years of the recruitment phase then decreased to near zero with the number of
      participants randomized to the study practically evaporating. In contrast, the
      bulimia studies screened a larger group of contacts and met monthly randomization
      goals in the time allotted for recruitment. Participants eligible for a study but
      with a barrier to participation occurred at a much higher rate in the anorexia
      study than in the bulimia studies. DISCUSSION: These results reveal a difficulty
      in planning recruitment from a small population such as partially recovered
      anorexics. A small population's total pool size diminishes faster than it is
      replenished, suggesting that future studies of anorexia nervosa may recruit more
      successfully from many sites in a short period rather than at a few sites over a
      long period.

PMID- 14705156
TI  - The recognition of emotion in the faces and voice of anorexia nervosa.
AB  - OBJECTIVE: The aim of this study was to examine emotional recognition (prosodic
      and visual) in anorexia nervosa. METHODS: Thirty people with anorexia nervosa and
      a comparison group of 30 healthy women were tested with facial and vocal stimuli
      that expressed specific emotions and they were given a neutral task. RESULTS: The
      group of women with anorexia nervosa was poor at emotional recognition. This was
      most marked for negative emotions in faces and for both positive and negative
      emotions in voices. This decreased ability to recognize negative affect in faces
      remained even after adjustment for confounding variables such as age, education,
      and depression. DISCUSSION: People with anorexia nervosa have difficulty
      recognizing emotions from facial expression and vocal tone. This may contribute
      to poor interpersonal communication and a lack of empathy, both of which are
      associated with anorexia nervosa patients.

PMID- 14705157
TI  - Thin ideals in music television: a source of social comparison and body
      dissatisfaction.
AB  - OBJECTIVE: The study investigated the impact of thin idealized images of women as
      presented in music television, a popular form of entertainment for young people.
      METHODS: A sample of 84 women viewed a videotape containing either appearance
      music videos (which emphasized appearance and featured thin and attractive women)
      or non-appearance music videos. The instructional set was also manipulated to
      encourage or discourage social comparison. RESULTS: Viewing the appearance music
      videos featuring thin women led to increased social comparison and body
      dissatisfaction. Regression analyses showed that the effect of video condition on
      body dissatisfaction was mediated by the level of comparison processing.
      DISCUSSION: The study demonstrated that the content of television programming can
      have negative consequences for women's body image. In addition, it offered social
      comparison processing as both a theoretic mechanism and a practical target for
      intervention.

PMID- 14705158
TI  - Effect of exposure to a forbidden food on eating in restrained and unrestrained
      women.
AB  - OBJECTIVE: The current study explored the effect of availability of a forbidden
      food on subsequent eating behavior in restrained and unrestrained women. METHOD:
      Thirty restrained and 30 unrestrained, normal-weight women were assigned randomly
      to one of two conditions, an experimental group that was exposed to a forbidden
      food (chocolate) for 24hr or a control group that was given no special
      intervention. At the end of the exposure period, all subjects completed an intake
      test of the forbidden food. RESULTS: Although subjects were instructed not to eat
      the food provided for the exposure period, women in the restrained group consumed
      a small quantity of the chocolate, whereas unrestrained women consumed none.
      Intake at test was greater in the temptation than in the control condition and
      restrained eaters consumed more than unrestrained eaters in both conditions.
      DISCUSSION: The results are discussed in terms of current theories of restrained
      eating and the possible interrelationships between eating regulation and
      cognition.

PMID- 14705159
TI  - Self-oriented and socially prescribed perfectionism in the Eating Disorder
      Inventory Perfectionism subscale.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the existence and the
      importance of the distinction between self-oriented and socially prescribed
      perfectionism in the Eating Disorder Inventory Perfectionism subscale (EDI-P).
      METHOD: Trait perfectionism, measured by the EDI-P, and eating disorder symptoms,
      measured by the 26-item Eating Attitudes Test, were examined in 220 university
      students (110 women and 110 men) belonging to a campus-based fitness facility.
      RESULTS: Confirmatory factor analysis indicated that, for both genders, the EDI-P
      is best represented by a multidimensional factor structure with three self
      oriented perfectionism items (EDI-SOP) and three socially prescribed
      perfectionism items (EDI-SPP). Structural equation modeling demonstrated that,
      for both genders, EDI-SOP and EDI-SPP are related independently to eating
      disorder symptoms. Moderational analysis indicated that, for women, the impact of
      EDI-SOP on eating disorder symptoms is dependent on the level of EDI-SPP.
      DISCUSSION: It is suggested that future research should acknowledge the empirical
      and theoretical implications of having EDI-SOP and EDI-SPP in the EDI-P. It is
      cautioned that EDI-SOP and EDI-SPP are a partial representation of an already
      published multidimensional model of trait perfectionism.

PMID- 14705160
TI  - Reliability of the Eating Disorder Examination in patients with binge eating
      disorder.
AB  - OBJECTIVE: This study examined the interrater and test-retest reliabilities of
      the Eating Disorder Examination (EDE) in patients with binge eating disorder
      (BED). METHOD: Interrater reliability and short-term (6-14 days) test-retest
      reliability of the EDE were examined in two study groups of 18 patients with BED.
      RESULTS: Interrater reliability was excellent for objective bulimic episodes and
      days (correlations above .98) and very good for the EDE scales, albeit somewhat
      variable (correlations range from .65 to .96). Test-retest reliabilities were
      very good for objective bulimic episodes (.70) and days (.71) and were good
      (significant) for the EDE scales, albeit somewhat variable (correlations range
      from .50 to .88). Interrater reliability was excellent for subjective bulimic
      episodes and days but test-retest reliabilities were unacceptable. CONCLUSIONS:
      These findings support the reliability of the EDE for patients with BED. The EDE
      has utility for assessing the number of large binge episodes (objective bulimic
      episodes), as well as the number of days during which large binge episodes
      occurred. The EDE also demonstrates very good interrater and test-retest
      reliabilities for assessing the associated features of eating disorders in
      patients with BED. The results for subjective bulimic episodes are consistent
      with previous studies, suggesting that these eating behaviors may not be reliable
      indicators of eating disorders.

PMID- 14705161
TI  - Comparison of self-report to interview assessment of bulimic behaviors among
      preadolescent and adolescent girls and boys.
AB  - OBJECTIVE: To compare self-report to interview assessment of bulimic behaviors
      among adolescents. METHOD: A sample of children in an ongoing study were
      recruited to complete in-depth telephone interviews in 1998 on bulimic behaviors
      (i.e., binge eating and purging). The sample comprised 449 girls and 50 boys.
      RESULTS: There was some over-reporting of bulimic behaviors on the 1998
      questionnaire (asking about 1997-1998) compared with the interview that may have
      been due to the shorter and nonoverlapping time frame in the interview compared
      with the questionnaire. Despite the overestimation, the questionnaire did an
      excellent job at classifying girls who did not purge (negative predictive values
      [NPV]: 0.99) or binge eat (NPV = 0.98). When purging on the interview was
      compared with purging on either the 1998 or 1999 questionnaires, the sensitivity
      increased substantially from 0.73 to 0.93. DISCUSSION: These findings suggest
      that a short self-report assessment can be used to screen children engaging in,
      or at risk of beginning to engage in, binge eating and purging.

PMID- 14705162
TI  - Body checking and its avoidance in eating disorders.
AB  - OBJECTIVE: One expression of the core psychopathology of eating disorders is the
      repeated checking and avoidance of shape or weight. Two studies are reported. The
      primary purpose of the first was to describe the phenomenology of such body
      checking and avoidance. The aim of the second was to compare body checking and
      avoidance in women with and without a clinical eating disorder. METHOD: In Study
      1, 64 female patients with clinical eating disorders participated in a
      semistructured interview assessing the features of body checking and avoidance.
      In the second study, a self-report questionnaire was used to compare body
      checking and avoidance in women with and without a clinical eating disorder (n =
      110). RESULTS: The majority (92%) of the patients in Study 1 checked their bodies
      to assess their shape or weight and this was associated significantly with eating
      disorder symptoms. In Study 2, the clinical group had significantly more body
      checking and avoidance than the comparison group, and there was a strong
      association between eating disorder psychopathology and body checking and
      avoidance. CONCLUSIONS: These findings support the view that body checking and
      avoidance are direct expressions of the overevaluation of shape and weight.
      Further work is needed to determine whether these expressions contribute to the
      maintenance of eating disorders.

PMID- 14705163
TI  - Body fat perception in eating-disordered men.
AB  - OBJECTIVE: We sought to assess the relative roles of body fat ideals and body fat
      perception in men with eating disorders. METHOD: We compared 27 men meeting
      criteria for a current eating disorder (17 with anorexia nervosa and 10 with
      bulimia nervosa), 21 male mountain climbers, and 21 control men, using a
      computerized test of body image, the "somatomorphic matrix." RESULTS: When asked
      to choose the body that they "ideally would like to have," men with eating
      disorders selected an image with body fat closely comparable to that chosen by
      the control men. On perceived body fat, however, the groups differed
      dramatically. The eating-disordered men perceived themselves to be almost twice
      as fat as they actually were, whereas the control subjects showed virtually no
      such distortion. These findings resemble those of a previous study of women,
      which found that women dieters showed abnormal body fat perception, but not body
      fat ideals, when compared with non-dieters. CONCLUSION: These observations
      suggest that distorted body perception, rather than body ideal, may be central to
      eating disorders in men. This distinction may be important for both research and
      therapy.

PMID- 14705164
TI  - Rating of figures used for body image assessment varies depending on the method
      of figure presentation.
AB  - OBJECTIVE: To determine the effect of method of figure presentation on figure
      rating scales used for body image assessment. METHODS: Ratings of current, ideal,
      and socially acceptable body sizes were elicited from 360 university students.
      Male and female figure drawings ranging from thin to obese were presented to
      subjects using one of three presentation methods. Figures were presented as an
      ordered array, an unordered array, or they were placed individually on cards that
      were fixed in order from thin to obese. RESULTS: Figure ratings were
      significantly different among methods for the selection of current and ideal
      figure and socially acceptable body sizes. DISCUSSION: The method of figure
      presentation had an influence on figure ratings. These findings suggest that the
      manner in which figures are presented to research participants for the evaluation
      of body image constructs may be responsible, in part, for the discordant results
      reported in the body image assessment literature. Future research is required to
      address potential reasons why the method of figure presentation results in
      different figure ratings.

PMID- 14705165
TI  - A young female patient with anorexia nervosa complicated by Mycobacterium szulgai
      pulmonary infection.
AB  - OBJECTIVE: Pulmonary infection with a rare atypical mycobacterium, Mycobacterium
      szulgai, was discovered during the treatment of anorexia nervosa in a 21-year-old
      Japanese woman without preexisting pulmonary disease. She had a long history of
      low body weight below 35 kg. METHODS: On admission, she was examined. She weighed
      23 kg and presented with hypoproteinemia, decreased levels of rapid turnover
      proteins, liver dysfunction, and decreased serum level of insulin-like growth
      factor-I. RESULTS: Although she had had neither clinical symptom specific for
      mycobacterium pulmonary infection nor inflammatory data, a chest roentgenogram
      showed an infiltrative shadow with cavity formation in the right upper lung
      field. Isolated bacteria from sputum was acid-fast bacilli and identified as M.
      szulgai using the DNA-DNA hybridization method. DISCUSSION: In anorexia nervosa
      patients with a long history of severe malnutrition, special attention must be
      paid to the possibility of opportunistic infections, even in the absence of
      symptoms or inflammatory data.

PMID- 14705166
TI  - Dihydropteridine reductase deficiency in man: from biology to treatment.
AB  - In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a
      cause of tetrahydrobiopterin (BH(4)) deficiency, leading to hyperphenylalaninemia
      (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients
      scattered worldwide have been reported and major progresses have been made in the
      understanding of physiopathology, screening, diagnosis, treatment, and molecular
      genetics of this inherited disease. Present knowledge on different aspects of
      DHPR deficiency, largely derived from authors' personal experience, is traced in
      this article.

PMID- 14705167
TI  - New antithrombin-based anticoagulants.
AB  - Clinically used anticoagulants are inhibitors of enzymes involved in the
      coagulation pathway, primarily thrombin and factor Xa. These agents can be either
      direct or indirect inhibitors of clotting enzymes. Heparin-based anticoagulants
      are indirect inhibitors that enhance the proteinase inhibitory activity of a
      natural anticoagulant, antithrombin. Despite its phenomenal success, current
      anticoagulation therapy suffers from the risk of serious bleeding. The need for
      safer and more effective antithrombotic agents clearly exists. The past decade
      has seen enormous effort directed toward discovering and/or designing new
      molecules with anticoagulant activity. These new molecules can be classified into
      (a). antithrombin and its mutants, (b). natural polysaccharides, (c). synthetic
      modified heparins and heparin-mimics, (d). synthetic oligosaccharides, and (e).
      synthetic non-sugar antithrombin activators. This review focuses on these efforts
      in designing or discovering new molecules that act through the antithrombin
      pathway of anticoagulation.

PMID- 14705168
TI  - Recent advances in selective opioid receptor agonists and antagonists.
AB  - Opioid analgesics provide outstanding benefits for relief of severe pain. The
      mechanisms of the analgesia accompanied with some side effects have been
      investigated by many scientists to shed light on the complex biological processes
      at the molecular level. New opioid drugs and therapies with more desirable
      properties can be developed on the bases of accurate insight of the opioid ligand
      receptor interaction and clear knowledge of the pharmacological behavior of
      opioid receptors and the associated proteins. Toward this goal, recent advances
      in selective opioid receptor agonists and antagonists including opioid ligand
      receptor interactions are summarized in this review article.

PMID- 14705169
TI  - KATP channel openers: structure-activity relationships and therapeutic potential.
AB  - ATP-sensitive potassium channels (K(ATP) channels) are heteromeric complexes of
      pore-forming inwardly rectifying potassium channel subunits and regulatory
      sulfonylurea receptor subunits. K(ATP) channels were identified in a variety of
      tissues including muscle cells, pancreatic beta-cells, and various neurons. They
      are regulated by the intracellular ATP/ADP ratio; ATP induces channel inhibition
      and MgADP induces channel opening. Functionally, K(ATP) channels provide a means
      of linking the electrical activity of a cell to its metabolic state. Shortening
      of the cardiac action potential, smooth muscle relaxation, inhibition of both
      insulin secretion, and neurotransmitter release are mediated via K(ATP) channels.
      Given their many physiological functions, K(ATP) channels represent promising
      drug targets. Sulfonylureas like glibenclamide block K(ATP) channels; they are
      used in the therapy of type 2 diabetes. Openers of K(ATP) channels (KCOs), for
      example, relax smooth muscle and induce hypotension. KCOs are chemically
      heterogeneous and include as different classes as the benzopyrans,
      cyanoguanidines, thioformamides, thiadiazines, and pyridyl nitrates. Examples for
      new chemical entities more recently developed as KCOs include cyclobutenediones,
      dihydropyridine related structures, and tertiary carbinols.

PMID- 14705170
TI  - In vitro investigation of detectability of colorectal lymph nodes and diagnosis
      of lymph node metastasis in colorectal cancer using B-mode sonography.
AB  - PURPOSE: The aim of this in vitro study was to assess the feasibility of using
      high-frequency sonography to identify colorectal lymph nodes and to diagnose
      colorectal lymph node metastasis. METHODS: In part 1 of this study, resected
      colorectal tissues from 13 patients with colorectal cancer were scanned in a
      water bath using B-mode sonography performed at high frequency (10 MHz) to
      identify lymph nodes. The colorectal tissues were then carefully dissected to
      remove all lymph nodes. Detectability was calculated as the ratio of the number
      of sonographically detected nodes to the total number of histopathologically
      confirmed nodes. Student's t test was performed to compare sizes between these
      groups; a p value of less than 0.05 was considered significant. In part 2, 4
      features of lymph nodes identified on B-mode sonography--size, shape, border, and
      echogenicity--and their combinations were evaluated for their ability to diagnose
      lymph node metastasis. Discriminant and receiver operating characteristic curve
      analyses were performed. RESULTS: In part 1, B-mode sonography performed in vitro
      detected 79 (48%) of the 165 histopathologically identified lymph nodes and 34
      (87%) of the 39 histopathologically identified metastatic nodes. The mean size,
      or mean longest axis (+/- standard deviation), of the sonographically detected
      nodes (6.4 +/- 2.9 mm) was significantly larger than that of undetected nodes
      (3.6 +/- 1.7 mm; p < 0.01). In part 2, the most effective feature distinguishing
      metastatic from nonmetastatic lymph nodes was echogenicity, followed by size,
      shape, and border. However, a combination of at least 2 features (eg,
      echogenicity and size) provided better distinction of nodes than did any 1
      feature. In the receiver operating characteristic curve of the 4-feature
      combination, an increase in sensitivity is accompanied by a decrease in
      specificity: at a sensitivity of 100%, specificities decreased to 60% or less.
      However, even with the optimal combination of features, the sensitivity and
      specificity did not both reach 85% at any operating point. CONCLUSIONS: The
      results of this node-by-node in vitro study show the current limitations and
      potential of sonography for assessing colorectal lymph nodes. High-frequency
      sonography may be insufficient for identifying lymph node metastasis in
      colorectal cancer.

PMID- 14705171
TI  - Timing of early amniocentesis as a function of membrane fusion.
AB  - PURPOSE: The purpose of this prospective study was to evaluate sonographically
      the timing of membrane fusion and to determine its possible effect on the timing
      of amniocentesis. METHODS: Between May 18, 1998, and January 31, 2002, the status
      of amnion fusion in pregnant patients at 9-15 weeks' menstrual age was identified
      in women who were to undergo obstetric sonography. Amniocentesis was performed if
      even a small area of fused membranes that could be traversed was identified; if
      the membranes were completely unfused, amniocentesis was delayed. The effect of
      membrane fusion in terms of the need to reschedule amniocentesis was evaluated.
      RESULTS: We examined a total of 594 patients. Membrane fusion occurred
      progressively with increasing menstrual age. One hundred six early amniocenteses
      were scheduled, and 70 were performed; the others were delayed because the
      membranes were unfused. Our requirement that an area of membrane fusion be found
      before we would perform amniocentesis resulted in rescheduling the procedure 24
      38% of the time. CONCLUSIONS: Membrane fusion, as seen sonographically, is a
      function of menstrual age. Even by 15 weeks, a portion of the amnion may be
      unfused with the chorion. Amniocenteses scheduled for early in the pregnancy may
      need to be delayed until later, when the membranes are at least partially fused,
      allowing safe passage of a needle. Delaying the procedure may incur higher
      expense but may be important in terms of lessening the risk involved.

PMID- 14705172
TI  - Role of sonographically guided fine-needle aspiration biopsy of adrenal masses in
      patients with lung cancer.
AB  - PURPOSE: The aims of this retrospective study were to determine the accuracy and
      safety of sonographically guided fine-needle aspiration biopsy (FNAB) in
      evaluating enlarged adrenal glands in patients with lung cancer and to correlate
      the metastatic involvement of the adrenal glands with the surgical stage of the
      primary lung tumor. METHODS: During an 11-year period, 64 patients with
      cytologically proven lung cancer had undergone sonographically guided FNABs of an
      adrenal mass. The accuracy of this method was assessed on the basis of cytologic
      findings and the safety, on the number of complications reported after FNAB. The
      location of the adrenal metastasis relative to the primary tumor (ipsilateral,
      contralateral, or bilateral) was correlated with the surgical stage of the
      disease. RESULTS: FNAB results were accurate in 58 of the 64 cases (91%), and the
      procedure was associated with no serious complications. In 6 (9%) of the 64
      patients, the FNAB specimen had been inadequate. Cytologic analysis of the
      aspirates revealed malignancy in 52 (90%) of the 58 patients in whom the FNAB
      specimen had been adequate for an accurate diagnosis. The adrenal metastases were
      ipsilateral in 21 patients, contralateral in 15, and bilateral in 16, for an
      ipsilateral-to-contralateral ratio of 1.4:1. Among patients with operable
      disease, an ipsilateral pattern of metastasis was present in 65%, whereas among
      those with inoperable disease, the ipsilateral pattern was present in only 31%.
      The difference between these 2 groups was statistically significant (p < 0.05).
      CONCLUSIONS: Sonographically guided FNAB is accurate and safe for evaluating
      enlarged adrenal glands in patients with lung cancer. Our results also suggest
      that a solitary ipsilateral adrenal metastasis in a patient with resectable
      primary lung cancer may represent a regional extension of the disease rather than
      systemic spread.

PMID- 14705173
TI  - Sonographic findings of active Clonorchis sinensis infection.
AB  - PURPOSE: The aim of this study was to document the characteristic sonographic
      findings of clonorchiasis for the diagnosis of active infection in an endemic
      area. METHODS: In a village in northeastern China, residents underwent fecal
      examinations for detection of Clonorchis sinensis eggs. Shortly thereafter,
      residents were examined with abdominal sonography. An experienced radiologist
      performed the sonographic examinations and analyzed the findings. Subjects whose
      fecal examinations were positive for eggs were considered to have active
      clonorchiasis; those whose examinations were negative for eggs were used as
      control subjects. The distinguishing sonographic features of active clonorchiasis
      were identified by stepwise logistic regression analysis. RESULTS: The study
      population comprised 457 subjects; fecal examinations revealed C. sinensis eggs
      in 316 and no eggs in 141. Four sonographic findings distinguished subjects with
      active clonorchiasis from control subjects: increased periductal echogenicity (p
      < 0.001; R = 0.11; sensitivity, 35%; specificity, 91%), floating echogenic foci
      in the gallbladder (p < 0.001; R = 0.09; sensitivity, 28%; specificity, 94%),
      diffuse dilatation of the intrahepatic bile ducts (p < 0.01; R = 0.03;
      sensitivity, 67%; specificity, 48%), and gallbladder distention (p < 0.05; R =
      0.02; sensitivity, 3%; specificity, 100%), in decreasing order of significance.
      Among these 4 sonographic findings, increased periductal echogenicity and
      floating echogenic foci in the gallbladder were more significantly associated
      with active infection than were the other 2. CONCLUSIONS: Increased periductal
      echogenicity and floating echogenic foci in the gallbladder were identified as
      the 2 most significant findings for the sonographic diagnosis of active C.
      sinensis infection.

PMID- 14705174
TI  - Doppler evaluation of the thyroid in pediatric goiter.
AB  - PURPOSE: The aim of this study was to identify any changes in Doppler parameters
      in the thyroid arteries of pediatric patients with a clinical diagnosis of goiter
      living in an area where goiter is endemic. PATIENTS AND METHODS: In this
      prospective study, 20 pediatric patients with simple endemic goiter and 20 age
      matched healthy subjects underwent sonographic examination. The resistance index
      (RI) and peak systolic velocity (PSV) on duplex sonography were measured from the
      inferior thyroid arteries, and the thyroid gland volume was recorded. Serum
      thyrotropin, free T3 hormone, and free T4 hormone levels were measured in both
      groups. RESULTS: The mean thyroid volume (+/- standard deviation) was
      significantly higher in the patients than in the healthy subjects (7.2 +/- 1.4 ml
      versus 3.2 +/- 1.1 ml; p < 0.01). The mean RI values for the thyroid arteries
      were significantly lower in the patient than in the control group (0.58 versus
      0.70, respectively; p < 0.05). The mean PSV of the thyroid arteries was
      significantly higher for the patients than for the healthy subjects (mean, 36.7
      cm/second versus 18.3 cm/second, respectively; p < 0.05). There was no
      correlation between the Doppler parameters and any of the hormone levels
      evaluated. CONCLUSIONS: In the arteries supplying the thyroid gland in a
      pediatric population, RIs were lower and PSVs higher in the patients with diffuse
      goiter than in the healthy control group. We discuss iodine deficiency as a
      possible mechanism for these changes.

PMID- 14705175
TI  - Sonographic findings in a patient with cystic hypersecretory duct carcinoma of
      the breast.
AB  - In this report, we describe a case of a rare form of intraductal carcinoma of the
      breast known as cystic hypersecretory duct carcinoma in a 49-year-old woman with
      a palpable mass and no history of breast disease. Mammography showed
      heterogeneous dense breast tissue with no definite abnormally increased density
      or microcalcifications. Gray-scale sonography detected multiple small aggregated,
      anechoic cysts with good through-transmission in the upper outer quadrant of the
      left breast, corresponding to the location of the palpable mass. The patient
      underwent an excision biopsy, and histopathologic examination of the surgical
      specimen revealed multiple cysts of different size containing an eosinophilic
      material resembling thyroid colloid. The locations of the cysts corresponded to
      those of the anechoic cysts detected on sonography. The epithelium lining the
      cysts showed micropapillary growth consistent with a diagnosis of cystic
      hypersecretory duct carcinoma. The mammographic and sonographic findings in this
      case differed somewhat from those reported previously for this rare form of
      breast carcinoma. Because the imaging findings and low-power microscopic
      appearance of the mass in our patient's case closely resembled those of some
      benign breast lesions, we recommend careful differentiation of this type of
      lesion using high-power microscopy during histopathologic evaluation.

PMID- 14705176
TI  - Popliteal artery pseudoaneurysm: a rare complication of brucellosis.
AB  - Brucellosis is still a public health problem, particularly in developing
      countries. After the primary infection subsides, a chronic stage characterized by
      nonspecific manifestations can develop, during which it may not be possible to
      isolate Brucella organisms and agglutination test titers may or may not be high.
      We present the case of a 49-year-old man who had only nonspecific symptoms and a
      2-month history of a pulsatile painful swelling in his right popliteal region. He
      had no history of trauma or surgery in that region, but he did ingest
      unpasteurized milk products. The patient's agglutination test titers were high,
      and Brucella melitensis was isolated from a bone marrow culture. Color Doppler
      sonography, T2-weighted MRI, and digital subtraction angiography were performed.
      Treatment with ultrasound-guided compression of the pseudoaneurysm failed because
      of high blood flow in its neck. Aneurysmectomy was undertaken, and the excised
      material was consistent with that from a mycotic pseudoaneurysm. Although both
      MRI and angiography provided useful information, the color Doppler sonography
      findings were characteristic of a pseudoaneurysm in the popliteal artery, and
      only that modality could detect the flow dynamics within the pseudoaneurysm.

PMID- 14705177
TI  - Doppler sonographic indices in diagnosing the nutcracker phenomenon in a
      hematuric adolescent.
AB  - Compression of the left renal vein between the aorta and the superior mesenteric
      artery, known as the nutcracker phenomenon, may cause gross or microscopic
      hematuria, pain in the flank, proteinuria, or a combination of these symptoms. We
      report the case of a hematuric adolescent diagnosed with a high index of
      suspicion by noninvasive Doppler sonography using the diagnostic indices of
      Doppler sonography established for adults with hematuria. Compression of the
      patient's left renal vein at the aortomesenteric portion and dilatation at the
      hilar portion were visualized by magnetic resonance angiography, which verified
      the diagnosis.

PMID- 14705178
TI  - Successful thrombolysis of a partially obstructed bileaflet prosthetic heart
      valve in the mitral position.
AB  - We describe the case of a woman who presented with dyspnea of abrupt onset and
      who had recently undergone replacement of the mitral valve with a bileaflet
      mechanical prosthesis. Transthoracic echocardiographic examination with spectral
      Doppler recording of transvalvular blood flow revealed a velocity spectrum
      consistent with obstruction. Transesophageal echocardiography demonstrated
      partial obstruction of the prosthetic valve due to immobilization of 1 hemidisc
      in the closed position. This immobilization was apparently caused by a small mass
      whose appearance was consistent with that of a thrombus. The patient was
      successfully treated by intravenous administration of a thrombolytic agent. This
      case demonstrates the value of transesophageal echocardiography in the selection
      of candidates for thrombolytic treatment in cases of thrombosis of a left-sided
      valve prosthesis.

PMID- 14705179
TI  - Protein-losing hypertrophic gastropathy: another cause of gastric wall thickening
      in children.
AB  - Protein-losing hypertrophic gastropathy (PLHG) is an uncommon, self-limited
      disease in young children that can produce generalized edema, hypoproteinemia,
      and nonspecific prodromic symptoms. Recently, Helicobacter pylori and
      cytomegalovirus infections have been reported to be associated with this
      condition. We present the case of an 18-month-old boy with PLHG and positive
      detection of H. pylori on fecal culture. Abdominal sonography demonstrated
      gastric wall thickening with preservation of the mucosal layers. Sonographic
      findings are useful for suggesting a diagnosis of PLHG and is also an effective,
      noninvasive technique for follow-up of children with this condition.

PMID- 14705181
TI  - The future of pharmaceutical engineering.

PMID- 14705182
TI  - High-throughput screening for stability and inhibitory activity of compounds
      toward cytochrome P450-mediated metabolism.
AB  - With the advent of combinatorial chemistry and high-throughput screening
      technology, thousands of molecules can now be rapidly synthesized and screened
      for biological activity against large numbers of protein targets, greatly
      increasing the speed with which lead compounds are identified during the early
      stages of drug discovery. However, rapid optimization of parameters that
      determine whether a high-affinity ligand or a potent inhibitor will become a
      successful drug remains a challenge in improving the efficiency of the drug
      discovery process. Parameters that define absorption, distribution, metabolism,
      and excretion properties of drug candidates are important determinants of
      therapeutic efficacy, and thus should be optimized during early stages of drug
      discovery. Although the speed with which drugs are screened for properties such
      as absorption, cytochrome P450 (CYP) inhibition, and metabolic stability has
      increased over the past several years, the screening rate/capacity is still
      several orders of magnitude lower than those for high-throughput methods used in
      lead identification, resulting in a bottleneck in the drug discovery process.
      This review discusses current methods used in the in vitro screening of drugs for
      their stability toward CYP-mediated oxidative metabolism. This is a critical
      screen in the drug discovery process because metabolism by CYP represents an
      important clearance mechanism for the vast majority of compounds, thus affecting
      their oral bioavailability and/or duration of action.

PMID- 14705183
TI  - Stability of PEGylated salmon calcitonin in nasal mucosa.
AB  - The purpose of this study was to evaluate the stabilization of salmon calcitonin
      (sCT) by PEGylation in nasal mucosa. Degradation of native sCT in the homogenates
      of rat nasal mucosa was investigated by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      initial cleavage of sCT was due to tryptic-like endopeptidase activity, and the
      subsequent degradation followed the sequential pattern of aminopeptidase
      activity. To prepare PEGylated sCT resistant to the proteolytic degradation, the
      lysine residues susceptible to tryptic activity were selectively PEGylated by
      controlling reaction pH. The PEGylated sCT showed strong resistance against
      enzymatic degradation in rat nasal mucosa, with 56-fold prolonged half-life
      compared with that of native sCT. In the MALDI-TOF MS spectrum, the PEGylated sCT
      did not show any degradation peak for incubation of 120 min in the homogenates of
      rat nasal mucosa. The improved stability may be responsible for enhancing nasal
      absorption of PEGylated sCT.

PMID- 14705184
TI  - Transporter-mediated renal handling of nafamostat mesilate.
AB  - Nafamostat mesilate (NM) is a serine-protease inhibitor that is rapidly
      eliminated from the circulation and accumulated in the kidney. This study was
      conducted to characterize the mechanism of NM transport in the kidney because a
      serious side effect of NM-induced hyperkalemia may be related to accumulation of
      NM in the kidney. Measurements of uptake of NM in vivo by the kidney uptake index
      (KUI) method and of transport in an in vitro-cultured LLC-PK1 cell system
      suggested the involvement of an organic cation transporter (OCT). To clarify the
      involvement of OCTs located in the basolateral membrane of proximal tubules, we
      evaluated NM transport by OCTs expressed in Xenopus laevis oocytes. The IC(50)
      values of NM on [(14)C]TEA ([(14)C]tetraethylammonium) uptake by rOCT1, rOCT2,
      and hOCT2 were 50, 0.5, and 20 microM, respectively, and NM was concluded to be a
      substrate of OCTs. To investigate the transport of NM across the brush-border
      membrane, we examined the uptake of NM into brush-border membrane vesicles
      (BBMVs) isolated from rat renal cortex. NM was taken up into the BBMVs, and the
      uptake was decreased by unlabeled NM and temperature, implying that a
      transporter(s) is also involved in NM transport across the apical membrane. NM
      was not a substrate of hOCTN1, hOCTN2, or P-gp, implying the involvement of some
      unknown transporter(s). Thus, renal accumulation of NM can be explained by the
      involvement of the basolateral OCTs, though the influence of the apical membrane
      transporter remains to be clarified.

PMID- 14705185
TI  - Anionic microparticles are a potent delivery system for recombinant antigens from
      Neisseria meningitidis serotype B.
AB  - The adsorption behavior of model proteins onto anionic poly(lactide-co-glycolide)
      (PLG) microparticles was evaluated. PLG microparticles were prepared by a w/o/w
      solvent evaporation process in the presence of the anionic surfactant dioctyl
      sodium sulfosuccinate (DSS). The effect of surfactant concentration and
      adsorption conditions on the adsorption efficiency and release rates in vitro was
      also studied. Subsequently, the microparticle formulation was tested to evaluate
      the efficacy of anionic microparticles as delivery systems for recombinant
      antigens from Neisseria meningitides type B (Men B), with and without CpG
      adjuvant. Protein (antigen) binding to anionic PLG microparticles was influenced
      by both electrostatic interaction and by other mechanisms, including hydrophobic
      attraction. The Men B antigens adsorbed efficiently onto anionic PLG
      microparticles and, following immunization in mice, induced potent enzyme-linked
      immunosorbent assay (ELISA) and serum bactericidal activity in comparison to alum
      adsorbed formulations. These Men B antigens represent an attractive approach for
      vaccine development.

PMID- 14705186
TI  - Pharmacokinetic characterization of dehydroevodiamine in the rat brain.
AB  - The objective of this study was to examine the kinetics of the distribution of
      dehydroevodiamine (DHED) in the rat brain. After an intravenous infusion of 15
      min (dose of 1-10 mg/kg), the temporal profiles of the plasma levels of DHED
      declined in a multiexponential manner. Moment analysis indicated that the
      clearance and steady-state volume of distribution for DHED were not statistically
      different with the dose, indicating that the pharmacokinetics for DHED is linear
      in the range examined. Nonlinear regression analysis of DHED concentrations in
      the plasma and the brain revealed that the linear kinetics into and out from the
      brain reasonably described the data and that the clearances for influx into and
      efflux from the brain were comparable. Transport clearances for DHED across MBEC4
      monolayers, an in vitro model of the blood-brain barrier, were also comparable
      for influx and efflux, and were independent of the medium concentration. The
      concentration of DHED in cerebrospinal fluid was negligible compared with that
      found in plasma, indicating that the drug is not primarily distributed to the
      brain via the blood-cerebrospinal fluid barrier. These observations indicate that
      DHED is transported from the systemic circulation to the brain via the blood
      brain barrier by linear kinetics.

PMID- 14705187
TI  - Release kinetics of catechins from chewing gum.
AB  - Chewing gums containing catechins were prepared by applying a novel solid
      dispersion and hot-melt fluid bed coating method. The effect of varying levels of
      Eudragit coating to the granules on the prolonged release of catechins from
      chewing gum was investigated. In vivo release profiles of catechins from the
      formulations were investigated to determine its release kinetics. Dissolution
      data were used as the primary basis for comparison. The equations with zero
      order, first-order, or square root of time release kinetics were used to fit
      data. The results showed that the releases of catechins from chewing gum were
      well extended with the growing coating level of Eudragit to the granules. The
      statistical analysis using nonlinear regression software suggested that the
      Higuchi equation describes the data better than others. The relatively high
      degree of fit using the Higuchi equation implies that the kinetic process is
      involved in the release of drug from the dosage form. A possible release
      mechanism based on this profile is presented in this report. This approach
      suggested the potential of using chewing gum as a promising controlled-release
      delivery system of drugs. The effect of polyvinyl acetates with different
      crosslinkings on the release profiles of catechins was also studied.

PMID- 14705188
TI  - Structure and generation mechanism of a novel degradation product formed by
      oxidatively induced coupling of miconazole nitrate with butylated hydroxytoluene
      in a topical ointment studied by HPLC-ESI-MS and organic synthesis.
AB  - In a petrolatum based topical ointment formulation containing miconazole nitrate
      (1) as the active ingredient and 2,6-di-t-butyl-4-methylphenol (BHT) as a vehicle
      antioxidant, an oxidatively induced coupling reaction between miconazole nitrate
      and BHT occurred to form a novel adduct 1-(3,5-di-tert-butyl-4-hydroxy-benzyl)-3
      [2-(2,4-dichloro-benzyloxy)-2-(2,4-dichloro-phenyl)-ethyl]-3H-imidazol-1-ium
      nitrate (2). The structure of 2 was established using high-performance liquid
      chromatography coupled with electrospray ionization mass spectrometry and was
      confirmed by comparing with a synthesized reference compound. The reaction
      proceeded through a quinone methide intermediate from BHT. Two synthetic methods
      were established for preparing 2.

PMID- 14705189
TI  - Detection of lipopolysaccharide in hemoglobin-vesicles by Limulus amebocyte
      lysate test with kinetic-turbidimetric gel clotting analysis and pretreatment of
      surfactant.
AB  - A method to quantitatively measure the bacterial endotoxin content
      (lipopolysaccharide, LPS) in phospholipid vesicles or liposomes is necessary
      because the conventional Limulus amebocyte lysate (LAL) test does not provide an
      accurate measurement due to the hydrophobic interaction of LPS and vesicles that
      shields the activity of LPS to clot the LAL coagulant. This interference was
      evident from isothermal titration calorimetry results in our study that clearly
      demonstrated the insertion of the LPS molecule into the phospholipid bilayer
      membrane. Hemoglobin-vesicles (HbVs; particle diameter = 251 +/- 80 nm; [Hb] = 10
      g/dL) are artificial oxygen carriers encapsulating a conc. Hb solution in
      phospholipid vesicles, and their oxygen transporting ability has been extensively
      studied. To accurately measure the LPS content in the HbV suspension, we tested
      the solubilization of HbV with deca(oxyethylene) dodecyl ether (C(12)E(10)), used
      to release the LPS entrapped in the vesicles, as a pretreatment for the
      succeeding LAL assay of the kinetic-turbidimetric gel clotting (detecting
      wavelength, 660 nm). The C(12)E(10) surfactant interferes with the gel clotting
      in a concentration-dependent manner, and the optimal condition was determined in
      terms of minimizing the dilution factor and C(12)E(10) concentration. We
      clarified the condition that allowed the measurement of LPS at >0.1 endotoxin
      units (EU)/mL in the HbV suspension. Moreover, the utilization of histidine
      immobilized agarose gel effectively concentrated the trace amount of LPS from the
      C(12)E(10)-solubilized HbV solution and washed out C(12)E(10) as an inhibitory
      element. The LAL assay with the LPS-adsorbed gel resulted in the detection limit
      of 0.0025 EU/mL. Pretreatment with C(12)E(10) would be applicable not only to
      HbVs but also to other drug delivery systems using phospholipid vesicles
      encapsulating or incorporating functional molecules.

PMID- 14705190
TI  - Determination of water-soluble acid distribution in poly(lactide-co-glycolide).
AB  - Determination of the kinetics of water-soluble degradation products inside
      poly(lactide-co-glycolide) (PLGA) delivery systems during polymer degradation is
      important to evaluate the polymer microclimate conditions, particularly
      microclimate pH changes for optimization of encapsulated drug stability. A pre
      derivatization high-performance liquid chromatography (HPLC) method was developed
      for separation and quantification of water-soluble acid impurities and
      degradation products in PLGA. Thin PLGA films (approximately 200 microm) were
      incubated in PBS/0.02% Tween 80, pH 7.4, for 6 weeks. Water-soluble monomers and
      oligomers were obtained from polymer films after repeated CHCl(3)/H(2)O
      extraction and then derivatized into bromophenacyl esters. With the common
      chromophore, the esters were separated and quantified by HPLC with increased
      ultraviolet (UV) sensitivity at 254 nm. The total amount of water-soluble acids
      in the extract was validated by potentiometric titration with tetrabutyl ammonium
      hydroxide. During the first 3 weeks of incubation of PLGA 50:50 (inherent
      viscosity = 0.63 dL/g), the principal water-soluble acids in the polymer were
      glycolic, lactic, and lactoyllactic acids, and an unknown oligomer. After 4 weeks
      of incubation, a large fraction of higher molecular weight oligomers was
      observed. Pre-derivatization HPLC can be used to accurately measure water-soluble
      acid distribution, and may be invaluable to examine the degradation behavior of
      PLGAs, including the underlying mechanism of polymer microclimate pH development.

PMID- 14705191
TI  - Probing drug solubilization patterns in the gastrointestinal tract after
      administration of lipid-based delivery systems: a phase diagram approach.
AB  - The formation of lyotropic phases resulting from the digestion of formulation
      lipids has a pronounced impact on the intestinal solubilization and resultant
      bioavailability of poorly water-soluble drugs. In this study, phase diagrams were
      produced to determine the phase behavior of the digestion products of common
      formulation lipids (C8:0, C12:0, and C18:1) under model physiological conditions.
      Pseudoternary phase diagrams were constructed using varying proportions of SEIF
      (Simulated Endogenous Intestinal Fluid) and fatty acid (FA) and monoglyceride
      (MG) (as representative exogenous lipid digestion products). A change from liquid
      crystal to colloidal liquid (containing mixed micelles and vesicles) was observed
      with decreasing FA/MG concentrations. The solubilization enhancement ratio (SER)
      afforded by these phases for a series of poorly water-soluble compounds
      (hydrocortisone and hydrocortisone esters, clogP = 1.4 to 5.2) was measured
      relative to the intrinsic solubility in buffer. Large increases in SER were
      observed in both lamellar (10-2000 fold) and cubic (10-30,000 fold) liquid
      crystal phases. Positive correlations were observed between the solubilization
      benefit provided by each phase and drug lipophilicity (r(2) > or = 0.9). These
      phase/solubility trends assist in our understanding of the mechanism by which
      poorly water-soluble drugs are trafficked across the intestinal colloidal species
      that form during the digestion of lipid-based drug delivery systems.

PMID- 14705192
TI  - Evaluation of the Malvern Spraytec with inhalation cell for the measurement of
      particle size distribution from metered dose inhalers.
AB  - The purpose of this study was to evaluate the Malvern Spraytec with inhalation
      cell attachment as a means of analyzing the particle size distribution of
      aerosols from pressurized metered dose inhalers (pMDIs). The aerosol particle
      size distribution of various commercially available, placebo, and experimental
      pMDI formulations was determined using Spraytec under various experimental
      conditions and the relevant data were compared with the Andersen cascade impactor
      data. The Spraytec volume median diameter (Dv 50) values for commercial
      chlorofluorocarbon- and hydrofluoroalkane (HFA)-based pMDIs were respectively
      smaller and higher compared with their reported mass median aerodynamic diameter
      values. It was possible to obtain a close agreement between Spraytec Dv 50 and
      the reported mass median aerodynamic diameter values for a solution-type pMDI
      formulation, Qvar 50, by equilibrating the pMDI to 55 degrees C before the
      measurement and using a 20-cm throat extension. Incorporation of a nonvolatile
      solvent propylene glycol (PG) in placebo pMDIs (15% w/w ethanol, 0.5-20.0% w/w PG
      in HFA 134a) showed an increase in Dv 50 with increasing concentration of PG.
      Furthermore, it was possible to obtain a correlation (R(2) = 0.8037) between
      Spraytec and Andersen cascade impactor data for the experimental nimesulide-pMDI
      formulations containing 0.1% w/w drug, 0.25-10% w/w PG, and 15% ethanol in HFA
      134a.

PMID- 14705193
TI  - Determination of volume of distribution at steady state with complete
      consideration of the kinetics of protein and tissue binding in linear
      pharmacokinetics.
AB  - The assumption of an instant equilibrium between bound and unbound drug fractions
      is commonly applied in pharmacokinetic calculations. The equation for the
      calculation of the steady-state volume of distribution V(ss) from the time curve
      of drug concentration in plasma after intravenous bolus dose administration,
      which does not assume an immediate equilibrium and thus incorporates dissociation
      and association rates of protein and tissue binding, is presented. The equation
      obtained V(ss) = (Dose/AUC)*MRT(u) looks like the traditional equation, but
      instead of mean residence time MRT calculated using the total drug concentration
      in plasma, it contains mean residence time MRT(u) calculated using the plasma
      concentration of the unbound drug. The equation connecting MRT(u) and MRT is
      derived. If an immediate equilibrium between bound and unbound drug fractions
      occurs, MRT(u) and MRT are the same, but in general, MRT(u) is always smaller
      than MRT. For drugs with high protein affinity and slow dissociation rate MRT(u)
      may be of an order of several hours smaller than MRT, so that V(ss) can be
      considerably overestimated in the traditional calculation.

PMID- 14705194
TI  - Fluorescence studies of the transformation of carbamazepine anhydrate form III to
      its dihydrate phase.
AB  - It has been found that both the anhydrous Form III and dihydrate phases of
      carbamazepine exhibit fluorescence in the solid state. The fluorescence intensity
      associated with the dihydrate phase was determined to be significantly more
      intense than that associated with the anhydrate phase, and this difference was
      exploited to develop a method for study of the kinetics of the aqueous solution
      mediated phase transformation between these forms. Studies were conducted at
      temperatures over the range 18-40 degrees C, and it was found that the phase
      transformation was adequately characterized by first-order reaction kinetics. The
      temperature dependence in the calculated rate constants was used to calculate an
      activation energy of 11.2 kcal/mol (47.4 cal/g) for the anhydrate-to-dihydrate
      phase conversion.

PMID- 14705195
TI  - Molecular mobility-based estimation of the crystallization rates of amorphous
      nifedipine and phenobarbital in poly(vinylpyrrolidone) solid dispersions.
AB  - The overall crystallization rates and mean relaxation times of amorphous
      nifedipine and phenobarbital in the presence of poly(vinylpyrrolidone) (PVP) were
      determined at various temperatures to gain further insight into the effect of
      molecular mobility on the crystallization rates of amorphous drugs and the
      possibility of predicting stability from their molecular mobility. Nifedipine-PVP
      (9:1 w/w) and phenobarbital-PVP (95:5 w/w) solid dispersions were prepared by
      melting and rapidly cooling mixtures of each drug and PVP. The amount of
      amorphous nifedipine remaining in the solid dispersion was calculated from the
      heat of crystallization,which was obtained by differential scanning calorimetry.
      The amount of amorphous phenobarbital remaining in the solid dispersion was
      estimated from the change in the heat capacity at its glass transition
      temperature (T(g)). The time required for the amount of amorphous drug remaining
      to fall to 90% (t(90)) was calculated from the profile of time versus the amount
      of amorphous drug remaining. The t(90) values for the solid dispersions studied
      were 100-1000 times longer than those of pure amorphous drugs when compared at
      the same temperature. Enthalpy relaxation of the amorphous drugs in the solid
      dispersions was reduced compared with that in the pure amorphous drugs,
      indicating that the molecular mobility of the amorphous drugs is reduced in the
      presence of PVP. The temperature dependence of mean relaxation time (tau) for the
      nifedipine-PVP solid dispersion was calculated using the Adam-Gibbs-Vogel
      equation. Parameters D and T(0) in this equation were estimated from the heating
      rate dependence of T(g). Similar temperature dependence was observed for t(90)
      and tau values of the solid dispersion, indicating that the information on the
      temperature dependence of the molecular mobility, along with the crystallization
      data obtained at around the T(g), are useful for estimating the t(90) of overall
      crystallization at temperatures below T(g) in the presence of excipients.

PMID- 14705196
TI  - Protection of salmon calcitonin breakdown with serine proteases by various
      ovomucoid species for oral drug delivery.
AB  - The current work compared protective effects of various ovomucoid species against
      salmon calcitonin (sCT) metabolism by serine proteases. sCT solutions (50 microM)
      were incubated at 37 degrees C with trypsin (0.5 microM), alpha-chymotrypsin (0.1
      microM), or elastase (0.48 microM) in 50 mM Tris buffer (pH 8.0) containing or
      lacking different concentrations of turkey ovomucoid (tOVM), duck ovomucoid
      (dOVM), or chicken ovomucoid (cOVM) and aprotinin. Caco-2 cell homogenate was
      also incubated with sCT and the contents of the proteases were assayed by using
      their specific substrates. Metabolites were identified by high-performance liquid
      chromatography, gel electrophoresis, and matrix-assisted laser desorption
      ionization mass spectrometry techniques. In the absence of inhibitors, there was
      a considerable degradation of sCT by the proteases. dOVM and tOVM increased the
      half-life of sCT with trypsin and alpha-chymotrypsin at enzyme-to-inhibitor ratio
      of 1:4 showing similar efficacy. dOVM was found to be superior to tOVM in
      protecting sCT from elastase. cOVM was ineffective in protecting sCT against
      alpha-chymotrypsin. Caco-2 cell homogenate degraded sCT, which was prevented by
      tOVM. sCT was cleaved into different molecular weight fragments with different
      proteases. In general, the metabolite formation decreased when inhibitor
      concentration increased. dOVM and tOVM effectively stabilized sCT against all
      three proteases. However, cOVM could not prevent the degradation by alpha
      chymotrypsin.

PMID- 14705197
TI  - Modeling of adhesion in tablet compression. II. Compaction studies using a
      compaction simulator and an instrumented tablet press.
AB  - Adhesion problems are usually not identified until prolonged compression runs are
      studied near the end of the drug development process. During tablet
      manufacturing, adhesion problems encountered are usually addressed by
      statistically designed experiments based on experience. It would be a significant
      benefit for the pharmaceutical industry if adhesion problems could be identified
      early in drug development based on molecular considerations of the drug substance
      and/or prototype formulations. Drug substance-punch face interactions were
      reported in the first of the articles in this series, and focused on the
      elucidation of adhesion problems in tablet compression. It was hypothesized that
      the intermolecular interactions between drug molecules and the punch face was the
      first step (or criterion) in the adhesion process, and that the rank order of
      adhesion during tablet compression should correspond with the rank order of these
      energies of interaction. That is, the interaction between the molecular structure
      of the drug and the metal surface determines the primary interaction event or
      relative potential for adhesion, while the mechanical processes and/or
      lubrication effects may subsequently impact the extent of adhesion. Molecular
      simulations and atomic force microscopy were used to establish the rank order of
      the work of adhesion of a series of profen compounds. The results predicted that
      the relative degree of drug substance-punch face adhesion should decrease in the
      order of ketoprofen > ibuprofen > flurbiprofen. In this study, the authors
      investigated whether the rank order of the work of adhesion established on the
      molecular level and interparticulate level holds true in the tableting
      environment by measuring tablet take-off force, ejection force, and visual
      observation of the punch surfaces for both pure drug compacts and formulated
      tablets. The compaction simulator was used for pure profen compacts, while the
      instrumented tablet press for formulated tablets. Due to the inability to extract
      the adhesion force component from the total ejection force measurement, tablet
      ejection force was not used as a criterion to judge the adhesion behavior of the
      model compounds. The criteria used for judgement of punch face adhesion were
      tablet take-off force and visual observation of the punch faces. The rank order
      of adhesion for both pure drug and formulated tablets was determined to follow
      the order of ketoprofen > ibuprofen > flurbiprofen. The effect of run time on
      adhesion behavior was also investigated. Therefore, the rank order of the punch
      face adhesion tendencies for the series of profen compounds was determined, and
      found to agree with the data from the predictive methods reported in the first
      article.

PMID- 14705198
TI  - An alternative approach based on artificial neural networks to study controlled
      drug release.
AB  - An alternative methodology based on artificial neural networks is proposed to be
      a complementary tool to other conventional methods to study controlled drug
      release. Two systems are used to test the approach; namely, hydrocortisone in a
      biodegradable matrix and rhodium (II) butyrate complexes in a bioceramic matrix.
      Two well-established mathematical models are used to simulate different release
      profiles as a function of fundamental properties; namely, diffusion coefficient
      (D), saturation solubility (C(s)), drug loading (A), and the height of the device
      (h). The models were tested, and the results show that these fundamental
      properties can be predicted after learning the experimental or model data for
      controlled drug release systems. The neural network results obtained after the
      learning stage can be considered to quantitatively predict ideal experimental
      conditions. Overall, the proposed methodology was shown to be efficient for ideal
      experiments, with a relative average error of <1% in both tests. This approach
      can be useful for the experimental analysis to simulate and design efficient
      controlled drug-release systems.

PMID- 14705199
TI  - Assessment of the effects of sodium dodecyl sulfate on the buccal permeability of
      caffeine and estradiol.
AB  - The concentration-dependent effects of sodium dodecyl sulfate (SDS) on the in
      vitro permeability of the buccal mucosa were assessed using caffeine (CAF) and
      estradiol (E(2)) as model hydrophilic and lipophilic markers, respectively. The
      permeability of CAF and E(2) through porcine buccal mucosa was determined in
      modified Ussing chambers, with and without exposure to different concentrations
      of SDS (0.01, 0.05, 0.1, and 1% w/v in physiological buffer). Permeability
      experiments were complemented with light microscopic evaluation of untreated and
      SDS-treated tissues. Additionally, the critical micellar concentration of SDS in
      the physiological buffer and the effect of SDS pretreatment on drug solubility
      were determined. Pretreatment of buccal mucosa with SDS 0.01% had no effect on
      CAF or E(2) permeability. SDS 0.05, 0.1, and 1% significantly enhanced CAF flux
      by a factor of 1.57, 1.63, and 1.81, respectively, and caused significant removal
      of superficial cells, as observed with light microscopy. Interestingly,
      pretreatment with SDS 0.05% did not affect E(2) flux, whereas SDS at > or =0.1%
      significantly reduced E(2) permeability, possibly as a result of micellar
      solubilization. These results demonstrate that the effect of SDS on buccal
      permeability depends on both the concentration of SDS used and the
      physicochemical properties of the permeant.

PMID- 14705200
TI  - Highly accurate nephelometric titrimetry.
AB  - A method that accurately indicates the end-point of precipitation reactions by
      the measurement of the relative intensity of the scattered light in the titrate
      is presented. A new nephelometric titrator with an internal nephelometric sensor
      has been devised. The work of the titrator including the sensor and change in the
      turbidity of the titrate and intensity of the scattered light are described. The
      accuracy of the nephelometric titrimetry is discussed theoretically. The
      titration of NaCl with AgNO(3) serves as a model. A relative error as well as
      deviation is within 0.2% under the experimental conditions. The applicability of
      the titrimetry in pharmaceutical analyses, for example, phenytoin sodium and
      procaine hydrochloride, is generally illustrated.

PMID- 14705201
TI  - Surfactant-facilitated crystallization of dihydrate carbamazepine during
      dissolution of anhydrous polymorph.
AB  - The influence of two structurally different anionic surfactants on the anhydrous
      to-dihydrate transformation of carbamazepine (CBZ) was investigated. The
      surfactants studied were sodium lauryl sulfate (SLS), a surfactant commonly used
      in compendial dissolution methods, and sodium taurocholate (STC), an important
      surfactant in the solubilization and absorption of drugs and lipids in the
      gastrointestinal tract. Results show that both surfactants promoted the
      crystallization of CBZ dihydrate [CBZ(D)] during dissolution of the anhydrous
      monoclinic polymorph [CBZ(A)]). Examination of crystal surfaces showed that SLS
      facilitated the surface-mediated nucleation of CBZ(D) on CBZ(A) crystals at
      surfactant concentrations below the critical micelle concentration (cmc).
      Solubilization of a dye and related color changes provided visual evidence for
      adsorbed SLS assemblies on CBZ(A) crystal faces below the cmc. Above the cmc,
      both surfactants promoted the transformation by increasing the bulk nucleation of
      CBZ(D). STC changed the crystal morphology of CBZ(D) from acicular to prismatic,
      depending on STC concentration. Such morphology changes originate from
      interactions between STC and molecular structures of CBZ(D) crystal faces that
      interfere with the formation of a hydrogen-bonded chain of water molecules and
      carboxamide dimers.

PMID- 14705202
TI  - The stability of 2-acetoxy-4-trifluoromethylbenzoic acid (Triflusal) in micellar
      pseudophase.
AB  - The new platelet antiaggregant Triflusal or 2-acetoxy-4-trifluoromethylbenzoic
      acid presents a structural analogy to acetylsalicylic acid (ASA). Alkaline
      hydrolysis of triflusal was studied in the presence and absence of cationic
      micelles of N-cetyl-N-ethyl-N,N-dimethylammonium bromide (CDEABr) at different
      KOH concentrations and different temperatures (25, 30, and 37 degrees C) using a
      spectrophotometric method. The influence of potassium bromide concentration upon
      alkaline hydrolysis at 25 degrees C is also discussed. At constant [KOH]
      pseudofirst-rate constant (k(obs)) decreased with increasing [CDEABr] at
      concentrations greater than the CMC and also decreased with increasing [KBr] at
      constant [KOH] and [CDEABr]. To explain the effect of cationic micelles of CDEABr
      upon alkaline hydrolysis, the pseudophase ion exchange model was used. The values
      of the micellar properties such as the critical micelle concentration, the degree
      of micellar ionization and the neutralized fraction of the head group obtained by
      conductivity measurements were determined previously.

PMID- 14705203
TI  - Diffusion modeling of percutaneous absorption kinetics: 3. Variable diffusion and
      partition coefficients, consequences for stratum corneum depth profiles and
      desorption kinetics.
AB  - Stratum corneum (SC) desorption experiments have yielded higher calculated steady
      state fluxes than those obtained by epidermal penetration studies. A possible
      explanation of this result is a variable diffusion or partition coefficient
      across the SC. We therefore developed the diffusion model for percutaneous
      penetration and desorption to study the effects of either a variable diffusion
      coefficient or variable partition coefficient in the SC over the diffusion path
      length. Steady-state flux, lag time, and mean desorption time were obtained from
      Laplace domain solutions. Numerical inversion of the Laplace domain solutions was
      used for simulations of solute concentration-distance and amount penetrated
      (desorbed)-time profiles. Diffusion and partition coefficients heterogeneity were
      examined using six different models. The effect of heterogeneity on predicted
      flux from desorption studies was compared with that obtained in permeation
      studies. Partition coefficient heterogeneity had a more profound effect on
      predicted fluxes than diffusion coefficient heterogeneity. Concentration-distance
      profiles show even larger dependence on heterogeneity, which is consistent with
      experimental tape-stripping data reported for clobetasol propionate and other
      solutes. The clobetasol propionate tape-stripping data were most consistent with
      the partition coefficient decreasing exponentially for half the SC and then
      becoming a constant for the remaining SC.

PMID- 14705204
TI  - Biodegradable nanoparticles containing protein-fatty acid complexes for oral
      delivery of salmon calcitonin.
AB  - Biodegradable nanoparticles containing salmon calcitonin (sCT) were formulated
      using protein-fatty acid complexes, and their in vitro transport against a Caco-2
      cell monolayer and the extent of in vivo oral uptake were assessed. Positively
      charged sCT was hydrophobically ion paired to form physical complexes with fatty
      acid, phospholipid, and surfactant. Among the complexes, sodium oleate was used
      to form sCT-oleate complexes, which were characterized and formulated into
      biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Endocytosis of
      sCT nanoparticles by Caco-2 cells was studied by flow cytometry. Transcytosis of
      sCT across the Caco-2 monolayer was also quantitated by an ELISA method. The sCT
      nanoparticles were orally administered to Sprague-Dawley rats, and serum sCT was
      monitored. Biodegradable polymeric nanoparticles containing a loading amount of
      sCT as high as 2.7% (w/w) were prepared based on the complexation of sCT with
      sodium oleate. A greater amount of sCT nanoparticles could be delivered into Caco
      2 cells compared with free sCT, and sCT could also be transported from the apical
      side to the basolateral side of the Caco-2 monolayer. In vivo experiments using a
      rat animal model showed the possibility of oral uptake of sCT. This study showed
      that physical complexation of sCT with amphiphilic molecules enabled the
      formation of sCT-loaded PLGA nanoparticles at a high loading efficiency and that
      sCT-PLGA nanoparticles were transported across the Caco-2 cell monolayer and were
      readily taken up in vivo following oral admistration.

PMID- 14705205
TI  - Effects of potassium bromide disk formation on the infrared spectra of dried
      model proteins.
AB  - The most common method of sample preparation for Fourier transform infrared
      spectroscopic analysis of proteins in the solid state is compression after mixing
      with potassium bromide (KBr). Recently, questions have arisen as to whether
      proteins are conformationally altered by this process. In this study, the amide I
      Fourier transform infrared spectra of two model proteins, lysozyme and alpha
      chymotrypsinogen, were measured before and after compression in KBr, and the
      effects of moisture exposure and the ratio of KBr to protein were examined.
      Contrary to earlier reports, compaction of the KBr/protein mixtures did not
      foster aggregation, and only minor apparent structural alterations were observed.

PMID- 14705206
TI  - Combined quantitative and mechanistic study of drug-membrane interactions using a
      novel 2H NMR approach.
AB  - Several analytical methods are available for determining the partition
      coefficients of drug compounds in model phospholipid membranes, but such methods
      provide little information at the molecular level about how the membrane affinity
      of drugs relates to their interactions with the lipid molecules. A new (2)H
      nuclear magnetic resonance (NMR) approach has been developed here that quantifies
      the affinity of (2)H-labeled small molecules for different phospholipid membranes
      and, simultaneously, provides information on the mechanism of the drug-membrane
      interaction. In the example given, (2)H NMR analysis of a weakly basic ion pump
      inhibitor found that the drug partitioned preferentially into membranes of
      predominantly unsaturated or short-chain phospholipids. The (2)H NMR analysis
      also suggested that the membrane specificity of the drug was directly correlated
      to the ability of its phenyl moiety to penetrate into the interior of the lipid
      bilayer. The (2)H NMR approach could be of value in guiding medicinal chemistry
      toward or away from structures promoting interactions with specific types of
      biological membranes.

PMID- 14705207
TI  - In vivo evaporation rate of benzyl alcohol from human skin.
AB  - The evaporation rate of benzyl alcohol from the human volar forearm under
      controlled conditions in vivo shows a similar dependence on airflow and time to
      that seen in earlier in vitro studies. After an initial time lag associated with
      the apparatus, evaporation rate over a 2-h time period post-dose was
      satisfactorily described by a single exponential decay with a rate constant
      proportional to airflow over the skin, nu. The cumulative percentage of dose
      evaporated after 2 h ranged from 16% at nu = 20 mL min(-1) to 52% at nu = 100 mL
      min(-1). The absorption rate constant determined by an analysis of the in vivo
      data was equivalent to that determined in vitro, whereas the evaporation rate
      constants were related by the inverse ratio of the headspace volumes. The latter
      finding suggests that a simple laminar flow model can satisfactorily describe
      evaporation in both systems over the range of airflows used.

PMID- 14705208
TI  - Defining remission in rheumatoid arthritis: what is it? Does it matter?

PMID- 14705209
TI  - Pain relief in osteoarthritis: the rationale for combination therapy.

PMID- 14705210
TI  - Are individual patient trials (n-of-1 trials) in rheumatology worth the extra
      effort?

PMID- 14705211
TI  - Rheumatological aspects of dance.

PMID- 14705212
TI  - New insights into prostaglandin biology.

PMID- 14705213
TI  - High diagnostic value of anticalpastatin autoantibodies in rheumatoid arthritis
      detected by ELISA using human erythrocyte calpastatin as antigen.
AB  - OBJECTIVE: To develop a quantitative method of measuring autoantibodies against
      human calpastatin in rheumatoid arthritis (RA) and to determine their diagnostic
      value compared with other autoimmune and articular diseases. METHODS: We
      performed a highly sensitive ELISA for IgG and IgM anticalpastatin autoantibodies
      in human sera using human erythrocyte calpastatin as an antigen. Samples were
      diluted 1:2000 for the measurement of IgG and 1:400 for IgM. RESULTS: IgG
      anticalpastatin antibodies were found in the sera of 48 of 58 patients (82.8%)
      with RA. In contrast, IgG anticalpastatin antibodies were found in the sera of
      only 2 of 11 (8.3%) patients with osteoarthritis (OA). Compared to sera from
      patients with other autoimmune diseases, anticalpastatin antibody sensitivity for
      RA was better than that of systemic lupus erythematosus (5.6%), systemic
      sclerosis (0%), mixed connective tissue disease (0%), and Sjogren's syndrome
      (20%). IgG anticalpastatin antibodies also showed high specificity (96.1%) for
      RA. Almost 90% of patients with RA were positive for IgG or IgM anticalpastatin
      antibodies. CONCLUSION: We have developed a simple, sensitive, specific, and
      quantitative ELISA for anticalpastatin antibodies that may have a high diagnostic
      value for RA.

PMID- 14705214
TI  - Tumor necrosis factor-alpha production is associated with less body cell mass in
      women with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the relationship between inflammatory cytokine production
      and body cell mass (BCM) in women with stable, medically well-controlled
      rheumatoid arthritis (RA). METHODS: Case-control study of 20 women with RA and 20
      healthy women matched for age, race, and body mass index (kg/m2). Tumor necrosis
      factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-6 production were
      measured by specific, non-cross-reacting ELISA of peripheral blood mononuclear
      cells (PBMC) cultured with and without 100 ng/ml of endotoxin. Total BCM was
      assessed by the reference method of whole-body counting of naturally occurring
      radioactive potassium-40. RESULTS: Patients with RA were cachectic, with 14% less
      BCM (p < 0.001) and higher TNF-alpha production (p < 0.05) than controls. TNF
      alpha production was inversely associated with BCM both without (r = -0.51, p =
      0.03) and with (r = -0.57, p = 0.01) endotoxin stimulation in patients but not in
      controls. In multivariate linear regression models, these inverse associations
      remained significant after adjustment for age and physical activity. No
      association was found for IL-1beta or IL-6 production in these models.
      CONCLUSION: Women with stable, medically well-controlled RA have lower than
      normal BCM that is inversely associated with elevated TNF-alpha production.

PMID- 14705215
TI  - Arthritis in mice: allogeneic pregnancy protects more than syngeneic by
      attenuating cellular immune response.
AB  - OBJECTIVE: We tested the hypothesis that collagen induced arthritis benefits more
      from allogeneic pregnancy than syngeneic pregnancy. METHODS: Arthritis was
      induced in female B10.RIII (H-2r) mice by injecting bovine type II collagen.
      Female mice were subsequently paired, one group with q-haplotype males (B10.Q)
      and the other with r-haplotype males (B10.RIII). The effect of q- and r-haplotype
      was measured by determining the acute phase reactant serum amyloid A (m-SAA),
      bovine anti-collagen type II antibodies (a-CBII), and the ratio of CD4/CD8 T
      lymphocytes during pregnancy and after delivery. Clinical assessment of arthritis
      was also performed. RESULTS: The number of mice with maximum severity of clinical
      arthritis was significantly higher in the syngeneic group (11/20 vs 5/21; p =
      0.04). Although we noted that in the allogeneic group the females had had a
      significantly higher level of a-CBII during pregnancy (p = 0.02), we also found
      that the ratio of CD4/CD8 was higher in the syngeneic group even if it was
      measured during (p = 0.04) or after gestation (p = 0.05). Taking into account all
      the cases of arthritis initiated in the post-gestational period there was no
      difference in m-SAA or in a-CBII between the 2 groups, but the ratio of CD4/CD8
      was higher in the syngeneic group measured during (p = 0.03) or post gestation (p
      = 0.02). CONCLUSION: Allogeneic pregnancy benefits more than syngeneic pregnancy
      by attenuating the cellular immune response, and the ratio of CD4/CD8 indicates
      the attenuation of cellular immunity when measured during gestation or post
      partum.

PMID- 14705216
TI  - Enhanced concentrations of interleukin 16 are associated with joint destruction
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the role of interleukin 16 (IL-16) in the development
      of rheumatoid arthritis (RA) and joint destruction. METHODS: We measured systemic
      IL-16 levels longitudinally in 39 patients with recent-onset RA, in 13 patients
      with initially undifferentiated arthritis who will develop RA over time, in 15
      patients with undifferentiated arthritis, and in 12 healthy controls, and
      correlated the levels with joint damage and disease activity. Systemic IL-16
      levels were measured by ELISA. Joint destruction was measured according to the
      Sharp method and the disease activity variables included C-reactive protein (CRP)
      and Disease Activity Score (DAS) measured at disease onset, and after one and 2
      years of followup. RESULTS: A significantly increased IL-16 level in RA patients
      at disease onset [median (25th-75th percentile) 45.2 (37.7-82.4) pg/ml] was
      observed compared to both controls [30.4 (24.4-37.0) pg/ml, p = 0.0008], and to
      patients with undifferentiated arthritis [29.0 (21.5-52.4) pg/ml; p = 0.005]. The
      IL-16 levels of the patients who presented with undifferentiated arthritis but
      who developed RA over time were also increased [47.9 (34.5-108.2) pg/ml] compared
      to the controls (p = 0.004) and to the patients who over time remained diagnosed
      with undifferentiated arthritis (p = 0.01). We found that high IL-16 levels
      correlated positively with joint destruction during the 2-year followup (p =
      0.02) and not with the disease activity variables. CONCLUSION: Our results
      suggest that the cytokine IL-16 plays a role in the disease process underlying RA
      and joint destruction.

PMID- 14705217
TI  - Value of Disease Activity Score 28 (DAS28) and DAS28-3 compared to American
      College of Rheumatology-defined remission in rheumatoid arthritis.
AB  - OBJECTIVE: To assess the criteria for remission based on Disease Activity Score
      28 (DAS28) and DAS28-3 (excluding patients' evaluation of disease activity)
      compared to American College of Rheumatology (ACR) preliminary criteria in
      established rheumatoid arthritis (RA), and to examine the value of each ACR
      criterion individually. METHODS: The EMECAR study was designed to assess the
      burden of comorbidity and inflammatory activity for RA in Spain. A random sample
      of 788 patients with RA from 34 Spanish centers was selected. Remission was
      defined by preliminary ACR criteria applied specifically and the clinical
      activity assessed by the DAS28 and the DAS28-3. A receiver operating
      characteristics curve analysis was performed to identify cutoff values with the
      highest usefulness in defining remission on both DAS indices. RESULTS: Thirty-two
      patients (4.1%) were in ACR-defined remission, 62 (7.9%) if fatigue was excluded
      from the criteria. The frequency of any single criterion that patients in
      remission fulfilled: no fatigue and joint pain by anamnesis in 31 patients
      (96.9%); morning stiffness < 15 min in 26 (81.3%); no swelling in joints in 21
      (65.6%); normal erythrocyte sedimentation rate (ESR) in 29 (90.6%); and no joint
      tenderness in 21 (65.6%) patients. The positive predictive value for remission of
      each criterion: normal ESR 6.5%; morning stiffness < 15 min 8.4%; no fatigue
      8.7%; no joint tenderness 13%; no swelling in joints 15.8%; and no joint pain by
      anamnesis 27.7%. The DAS28 cutoff values with higher discriminatory power for
      remission were 3.14 (sensitivity 87%; specificity 67%) when all the ACR criteria
      were used, and 2.81 (sensitivity 84%; specificity 81%) when fatigue was omitted.
      The equivalent cutoffs for the DAS28-3 were 3.52 (sensitivity 84%; specificity
      66%) and 2.95 (sensitivity 82%; specificity 83%), respectively. CONCLUSION: DAS28
      and DAS28-3 are good tools to define remission in established RA. No joint pain
      by anamnesis is the criterion with the highest value in defining remission, while
      normal ESR, an absence of morning stiffness, and fatigue are the least effective.

PMID- 14705218
TI  - Participation in paid and unpaid work by adults with rheumatoid arthritis.
AB  - OBJECTIVE: To define determinants of participation in paid and unpaid work by
      adults with rheumatoid arthritis (RA). METHODS: A survey was designed in
      consultation with working age (< 65 yrs) adults with RA and sent to 269 patients
      recruited through 5 rheumatology practices. Hours worked "last week" was the
      measure of participation in employment and unpaid work (household, home
      maintenance, caregiving, studying, and volunteering). Potential determinants,
      conceptually organized as attributes of the person, environment, or occupation,
      were ascertained. RESULTS: Recruitment response rate was 40% of patients invited,
      and 89% of those recruited submitted complete surveys. The 239 respondents were
      mostly women (81%), with mean age 50 years and duration of RA 13 years.
      Respondents reported an average of 47 hours of work: 19 paid and 28 unpaid hours.
      Regression analyses indicated more hours of paid work were associated with
      psychologically demanding work, higher social function, less pain, being male,
      managerial job type, and lower ratings of occupational balance. More hours of
      unpaid work were associated with more children in the household, greater
      perceived physical and psychological demand of the work, social support from
      family, and having a post-secondary education. Work limitations, reported by 73
      respondents, were associated with lower functional status, more pain, and less
      psychologically demanding work. CONCLUSION: Factors associated with greater
      participation in paid work differed from those associated with unpaid work. Work
      limitation affects both paid and unpaid workers. Work-related rehabilitation and
      education programs may be enhanced by addressing factors identified by this
      sample of paid and unpaid workers.

PMID- 14705219
TI  - Comorbidity in patients with rheumatoid arthritis: effect on health-related
      quality of life.
AB  - OBJECTIVE: To describe the extent of somatic comorbid conditions in patients with
      rheumatoid arthritis (RA) and to assess the influence of comorbidity on health
      related quality of life (HRQOL). METHODS: A 2-year followup study on health and
      HRQOL was conducted among 679 patients with RA with varying disease duration.
      Data were collected by means of questionnaires and clinical examinations at
      baseline and at 2-year followup. Comorbidity was measured by a self-administered
      questionnaire including 17 chronic diseases. HRQOL was assessed with the RAND-36.
      The effect of incident comorbid conditions on HRQOL was investigated with linear
      regression analyses. RESULTS: At least one comorbid condition was reported at
      baseline by 56% of patients. Significant differences in prevalence rates with the
      Dutch population were found. The effect of comorbidity on HRQOL depended on both
      the type of comorbid condition and the dimension of HRQOL. Gastrointestinal (GI)
      diseases, cancer, dizziness with falling (and less severe chronic pulmonary
      disease and heart complaints) resulted in significant adverse changes in HRQOL.
      For the other conditions under study no influence could be detected. CONCLUSION:
      Our results indicate that measuring comorbidity by a summary count, assuming an
      overall equally large effect of each comorbid condition, may not reveal the real
      effect. With respect to clinical practice, our results emphasize the relevance
      for health care providers to be aware of specific comorbid conditions exposing
      patients with RA at risk for additional impairment of HRQOL, and to be aware of
      interactions with RA that may be unique.

PMID- 14705220
TI  - Ability of foot radiographs to predict rheumatoid arthritis in patients with
      early arthritis.
AB  - OBJECTIVE: In a cohort of patients with early arthritis, to evaluate how well
      foot radiographs at study inclusion predicted a diagnosis of rheumatoid arthritis
      (RA) 2 years later. METHODS: A cohort of patients with arthritis of less than one
      year duration was evaluated in a multicenter study and followed for 30 +/- 11
      months. An observer blinded to patient data read all 149 hand and foot
      radiographs done at study inclusion, using item 7 of the 1987 American College of
      Rheumatology (ACR) criteria for RA and Sharp's method to score erosions and joint
      space narrowing. RESULTS: The kappa coefficient for the 1987 ACR item 7 was 0.52
      for bony decalcification and 0.87 for erosions. Intra and interobserver
      correlation coefficients for Sharp's scores ranged from 0.90 to 0.98. Erosions at
      the feet were significantly associated with RA. The item 7 erosion component at
      the feet was more specific than the full item 7 (97.5% vs 94%; p = 0.01). Sharp's
      erosion score at the feet was not better than the erosion component of item 7
      (sensitivity 18%; specificity 97.5%). Combined use of radiographs of the hands
      and feet improved the diagnostic performance of the item 7 erosion component;
      (sensitivity and specificity of item 7 erosions at the hands combined with the
      feet were 32.5% and 94.5%, respectively). CONCLUSION: The "erosion" criterion at
      the feet had the best diagnostic performance and was significantly associated
      with a diagnosis of RA. Combining hand and foot radiographs improved diagnostic
      performance.

PMID- 14705221
TI  - Nutrient intake and diet quality in patients with systemic lupus erythematosus on
      a culturally sensitive cholesterol lowering dietary program.
AB  - OBJECTIVE: To evaluate the effect of a culturally sensitive cholesterol lowering
      dietary program on energy, protein, fiber, vitamin and mineral intake, diet
      quality, and hemoglobin levels in patients with systemic lupus erythematosus
      (SLE). METHODS: Seventeen patients with SLE were randomized to a Step II diet
      intervention group or a control group for 12 weeks. The diet intervention was
      made up of weekly group sessions during the first 6 weeks followed by telephone
      counseling every 2 weeks for the last 6 weeks. Food intake was assessed by 3-day
      food record at baseline, 6, and 12 weeks. Diet quality was assessed by expressing
      the nutrients as a percentage of the Dietary Reference Intakes of the US National
      Academy of Sciences, or as a percentage of the nutrient guidelines by the
      National Cholesterol Education Program, Adult Treatment Panel III. Between- and
      within-group changes in nutrient intakes were assessed by repeated measures
      ANOVA. RESULTS: The changes in nutrient intakes were not significantly different
      between the groups for any of the nonfat nutrients except vitamin B12 (p = 0.05),
      which decreased in the diet group and increased in the control group. Within
      group analysis showed a significant reduction (p = 0.0003 to 0.02) in the diet
      group in energy and sodium intake at 6 and 12 weeks and B12 intake at 12 weeks
      compared to the respective baseline values (28-32%, 37-41%, and 43%,
      respectively). Sodium intake decreased to 66-71% of the total sodium allowance (<
      2400 mg per day) in the diet group. The intervention was successful in
      maintaining adequate intakes or even increasing intakes of most nutrients except
      B12, dietary fiber, folate, calcium, and iron, which were slightly higher or
      below 67% of the Dietary Reference Intakes or other dietary guidelines. Anemia,
      as assessed by hemoglobin levels, was present throughout the study and did not
      correlate with iron intake. CONCLUSION: This culturally sensitive cholesterol
      reducing diet program was successful in decreasing sodium intake and maintaining
      adequate intakes of most nutrients except B12, dietary fiber, iron, calcium, and
      folate. Future intervention studies in patients with SLE need to pay special
      attention to these nutrients and the presence of anemia.

PMID- 14705222
TI  - N-acetyl transferase genotypes in relation to risk of developing systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine the association between N-acetyl transferase (NAT) genotype
      (NAT1 and NAT2) and risk of developing systemic lupus erythematosus (SLE).
      METHODS: DNA samples were collected from 243 recently diagnosed cases and 298
      controls enrolled in a population based case-control study conducted in 60
      counties in North Carolina and South Carolina, USA. RESULTS: There was no
      association between SLE and NAT1 genotype (OR 0.96, 95% CI 0.65, 1.4 for the
      presence of a *10 allele) or NAT2 genotype (OR 1.1, 95% CI 0.73, 1.6 for the slow
      compared with fast-acetylation genotype). We saw some evidence of interaction
      between NAT genotypes and use of hair dyes (a source of arylamines), with higher
      risk seen among hair dye users who had both the *10 NAT1 allele and the NAT2 slow
      acetylation genotype (OR 2.9, 95% CI 1.2, 6.9 in this subgroup compared with all
      others). CONCLUSION: Our results suggest that although there is little overall
      association between NAT genotypes and risk of developing SLE, the interaction
      between NAT1 and NAT2 and specific exposures such as hair dyes may be important.
      This finding highlights the need to consider exposure when assessing genetic
      susceptibility.

PMID- 14705223
TI  - Interleukin 1alpha single-nucleotide polymorphism associated with systemic
      sclerosis.
AB  - OBJECTIVE: In systemic sclerosis (SSc), constitutive expression of the
      proinflammatory and fibrogenic cytokine interleukin 1alpha (IL-1alpha) by dermal
      fibroblasts from the affected skin has been observed. We investigated the
      association of a single-nucleotide polymorphism at position -889 in the IL-1alpha
      gene in patients with SSc. METHODS: Genotyping of IL-1alpha-889 polymorphism was
      performed in 46 patients with SSc and in 150 healthy controls by polymerase chain
      reaction with sequence-specific primers. All subjects were unrelated Slovak
      Caucasians. RESULTS: In SSc patients, carriers of the IL-1alpha-889 T allele were
      significantly overrepresented in comparison with controls (63.0% vs 42.0%; p =
      0.01, OR 2.3, 95% CI 1.2-4.6). The frequency of the IL-1alpha-889 T allele was
      increased in SSc patients (38.0%) in comparison with controls (25.7%; p = 0.02).
      CONCLUSION: The IL-1alpha-889 polymorphism, previously shown to predispose to
      increased IL-1 protein expression, may be involved in susceptibility to SSc.

PMID- 14705224
TI  - Ethnic differences in cytotoxic T lymphocyte associated antigen 4 genotype
      associations with systemic sclerosis.
AB  - OBJECTIVE: To determine the role of cytotoxic T lymphocyte associated antigen 4
      (CTLA-4) genetic polymorphisms in susceptibility to systemic sclerosis (SSc,
      scleroderma). METHODS: The study population consisted of 293 African American and
      Caucasian patients with SSc and matched controls. Subjects were genotyped for
      allelic determinants at 4 polymorphic sites: 3 in the promoter region (positions 
      318, -1661, -1722) and one in the first exon (position +49) of the CTLA-4 gene,
      using polymerase chain reaction (PCR) restriction fragment length polymorphism
      (RFLP) methods. Genotype frequencies were compared using Pearson's chi-square or
      Fisher's exact test. RESULTS: In African American patients, the frequency of AG
      heterozygotes at position +49 was significantly higher than in controls (71% vs
      36%, p = 0.003; OR = 4.37), while the frequency of AA homozygotes was
      significantly lower in patients than in controls (29% vs 61%, p = 0.007; OR =
      0.26). The distribution of CTLA-4 alleles at other loci did not differ
      significantly between patients and controls. CTLA-4 genotypes were not associated
      with SSc in Caucasians. No differences in CTLA-4 genotype distributions were
      observed between patients with the limited and diffuse forms of the disease.
      CONCLUSION: Our data show that the exon 1 (+49) polymorphism of the CTLA-4 gene
      is associated with systemic sclerosis in African Americans.

PMID- 14705225
TI  - Multiplex reverse transcription polymerase chain reaction assessment of
      sialyltransferase expression in peripheral blood mononuclear cells in systemic
      sclerosis.
AB  - OBJECTIVE: To assess sialyltransferase expression in peripheral blood mononuclear
      cells (PBMC) of patients with systemic sclerosis (SSc) and to correlate this
      expression with the clinical features of the disease. METHODS: Using a multiplex
      reverse transcription polymerase chain reaction (RT-PCR) method, we
      simultaneously measured the expression of 5 sialyltransferases (ST3Gal IV, ST3Gal
      III, ST3Gal I, ST3Gal II, and ST6Gal I) and of one reference housekeeping gene,
      Tata box binding protein (TBP), in PBMC of 28 patients with SSc and 18 healthy
      controls. Expression of each sialyltransferase was defined by the ratio
      sialyltransferase amplification product intensity/TBP amplification product
      intensity, and was evaluated according to the skin sclerosis extension and the
      presence of lung fibrosis and/or of pulmonary hypertension. RESULTS: ST3Gal I and
      ST6Gal I expressions were lower in patients with SSc than in healthy controls
      (median 0.48 vs 1.30, p < 0.0001, and 0.71 vs 1.96, p < 0.01, respectively). No
      difference was observed for ST3Gal III and ST3Gal IV expression. ST3Gal IV/ST6Gal
      I ratio was higher in SSc patients than in controls (0.37 vs 0.28, p = 0.03).
      ST3Gal II was either weakly or more often not expressed in both groups. Ten
      patients had isolated pulmonary hypertension. They had higher ST3Gal IV
      expression than patients without pulmonary hypertension (0.73 vs 0.29, p = 0.04)
      and a higher ST3Gal IV/ST6Gal I ratio than patients without pulmonary
      hypertension (1.03 vs 0.27, p = 0.03) and controls (1.03 vs 0.28, p = 0.02). No
      difference was found in the sialyltransferase expression and soluble E-selectin
      concentration according to the cutaneous sclerosis extension or the presence of
      lung fibrosis. CONCLUSION: Sialyltransferase expression is modified in PBMC of
      patients with SSc compared to healthy subjects. Low ST6Gal I expression
      associated with normal ST3Gal IV expression, resulting in a higher ST3Gal
      IV/ST6Gal I ratio, suggests an enhanced expression of Sialyl-LewisX at the
      surface of PBMC in SSc, and therefore an active interaction between activated
      endothelial cells and PBMC through the binding between E-selectin and Sialyl
      LewisX. This suggested that higher expression of Sialyl-LewisX concerned patients
      with isolated pulmonary hypertension more specifically. Binding between PBMC
      surface Sialyl-LewisX and activated endothelial cell E-selectin might therefore
      play a role in the pathogenesis of SSc-related isolated pulmonary hypertension.

PMID- 14705226
TI  - Etanercept in the treatment of patients with primary Sjogren's syndrome: a pilot
      study.
AB  - OBJECTIVE: This pilot study evaluated the effect of anti-tumor necrosis factor-a
      antiinflammatory treatment with etanercept (Enbrel(R)) on sicca, systemic, and
      histological signs in patients with primary Sjogren's syndrome (SS). METHODS:
      Fifteen patients with well defined primary SS were treated with 25 mg etanercept
      subcutaneously twice per week during 12 weeks, with followup visits at Weeks 18
      and 24. Evaluation measures included a Multidimensional Fatigue Inventory (MFI)
      questionnaire, serological monitoring, salivary flow tests, Schirmer test, rose
      bengal cornea staining, and tear film breakup time. A sublabial minor salivary
      gland biopsy was performed at baseline and at Week 12 and lymphocytic focus score
      and percentage IgA-containing plasma cells (IgA%) were assessed. RESULTS: No
      increase of salivary or lachrymal gland function was observed in any participant.
      In 4 patients a decrease of fatigue complaints was noted, which was also
      reflected by decreased scores in the MFI questionnaire. Reduced erythrocyte
      sedimentation rate was observed in 3 of 4 patients with reduced fatigue. No
      significant change of lymphocyte focus score or IgA% was observed. A repeated
      treatment up to 26 weeks showed the same results. CONCLUSION: A 12-week or
      prolonged treatment of etanercept 25 mg twice weekly did not appear to reduce
      sicca symptoms and signs in SS. However, etanercept treatment may be beneficial
      in a small subgroup of SS patients with severe fatigue. Etanercept 25 mg twice
      weekly did not affect minor salivary gland biopsy results.

PMID- 14705227
TI  - Takayasu's arteritis: vascular interventions and outcomes.
AB  - OBJECTIVE: To provide an analysis of outcomes of vascular interventions in 20
      patients with Takayasu's arteritis (TA) who received care at the Cleveland Clinic
      Foundation between 1979 and 2001. METHODS: We performed a retrospective chart
      review. The primary outcome measure of our review was patency of vessels as
      assessed by repeat invasive angiography or magnetic resonance angiography. The
      secondary outcome measures included periprocedural complications, morbidity, and
      mortality. Interventions included bypass grafts, patch angioplasty,
      endarterectomy, percutaneous transluminal angioplasty (PTA), or stent placement.
      RESULTS: Sixty-two revascularization procedures were performed in 20 patients.
      Followup evaluations were available for 52 procedures. Eleven of 31 bypass grafts
      restenosed or occluded between one day to 168 months after surgery. Three of 7
      PTA and 5 of 7 stents restenosed or became occluded after 1-72 months and 2-45
      months of followup, respectively. There were no deaths associated with
      revascularization procedures. CONCLUSION: Despite providing short term benefit,
      endovascular revascularization procedures are associated with a high failure rate
      in patients with TA.

PMID- 14705228
TI  - Infliximab therapy for rheumatic diseases in patients with chronic hepatitis B or
      C.
AB  - OBJECTIVE: To describe the safety of tumor necrosis factor-a blockade in 2
      patients with inflammatory rheumatic disease with chronic hepatitis B and C.
      METHODS: We used infliximab therapy in 2 patients with chronic inflammatory joint
      disease and chronic hepatitis B or C. We describe the clinical and laboratory
      test data obtained in these patients during the first year of treatment. Disease
      activity, liver function tests, and HCV and HBV status were evaluated before
      infliximab therapy was started and were reevaluated before each infusion. Liver
      biopsy was performed in both patients before infliximab therapy. RESULT: After
      more than one year of treatment, no worsening in liver function or virological
      status was observed, while a dramatic clinical improvement of joint disease was
      observed in both patients. CONCLUSION: These cases suggest that infliximab
      therapy may be safe in some quiescent or controlled chronic HBV or HCV infection.

PMID- 14705229
TI  - Expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in pigmented villonodular synovitis suggests their potential
      role for joint destruction.
AB  - OBJECTIVE: Pigmented villonodular synovitis (PVNS) is an uncommon idiopathic,
      proliferative synovial disease. Since matrix metalloproteinases (MMP) are assumed
      to play an important role in the pathogenesis of PVNS, we examined the expression
      and activity of MMP and tissue inhibitor of metalloproteinases (TIMP) in PVNS.
      METHODS: Synovial tissue samples were obtained from 10 patients with PVNS (knee
      8, ankle 2) and 4 patients each with rheumatoid arthritis (RA) or osteoarthritis
      (OA) for comparison. Protein deposition and mRNA expression were determined by
      conventional immunohistochemical studies and reverse transcription-polymerase
      chain reaction (RT-PCR), respectively. Gelatin zymography was performed for
      detection of gelatin-degrading activity. The quantity of MMP and TIMP was
      measured by ELISA. RESULTS: Intense immunostaining for MMP-1 was detected in both
      the multinucleated giant cells and mononuclear cells, whereas TIMP-1 was weakly
      positive. MMP-9 immunostained predominantly in the multinucleated cells, whereas
      other MMP and TIMP were weakly detected. RT-PCR analysis showed that mRNA
      expression of MMP-9 was stimulated in PVNS, whereas MMP-2 mRNA was not, compared
      to RA or OA. The gelatin zymogram indicated protease activities predominantly at
      92 kDa and 67 kDa. In accord with the immunostaining results, the amount of MMP-1
      and MMP-9 protein was significantly higher than that of TIMP-1 and MMP-2,
      respectively. CONCLUSION: We characterized the expression and activity of MMP in
      PVNS and observed that PVNS tissues predominantly produce MMP-1 and MMP-9. Given
      that PVNS occasionally induces joint destruction, stimulated expression of MMP-1
      and MMP-9 may contribute to the invasive activity and the bone and cartilage loss
      in PVNS.

PMID- 14705230
TI  - Fat suppression magnetic resonance imaging in shoulders of patients with
      polymyalgia rheumatica.
AB  - OBJECTIVE: To evaluate the sites of inflammatory process in the shoulders of
      patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic
      resonance imaging (MRI). METHODS: Six consecutive, untreated new patients with
      PMR were investigated. Five patients with early rheumatoid arthritis (RA) and 4
      patients with early psoriatic arthritis (PsA) with bilateral shoulder symptoms
      served as a control group. Bilateral shoulder fat-suppressed MRI sequences were
      performed in all patients and controls. We evaluated the presence of joint
      synovitis, bursitis, tenosynovitis, and bone and soft tissue edema. RESULTS:
      Bilateral subacromial/subdeltoid bursitis was found in all patients with PMR, in
      1/5 (20%) patients with RA (p < 0.05), and in none with PsA (p < 0.02).
      Glenohumeral synovitis was present in all case and controls. Biceps tenosynovitis
      was observed in 4/6 (67%) patients with PMR, in 4/5 (80%) with RA (not
      significant, NS), and in all 4 patients with PsA (NS). No evidence of bone edema
      adjacent to the joint capsule and entheseal insertions or in the soft tissues was
      present in either cases or controls. CONCLUSION: The absence of extracapsular
      abnormalities in the early shoulder disease of PMR does not confirm the
      hypothesis of a capsular-based disorder.

PMID- 14705231
TI  - Radiological scoring methods in ankylosing spondylitis. Reliability and change
      over 1 and 2 years.
AB  - OBJECTIVE: To compare reliability and change over time of radiological scoring
      methods in ankylosing spondylitis (AS). METHODS: Two trained observers scored 217
      sets of radiographs from baseline and from one and 2 years' followup. Sacroiliac
      (SI) joints were grade 0-4 by the New York method and Stoke Ankylosing
      Spondylitis Spine Score (SASSS). Hips and cervical and lumbar spine were graded 0
      4 by Bath Ankylosing Spondylitis Radiology Index (BASRI). BASRI spinal scores and
      New York SI are combined into BASRI-spine (score 2-12) and with the addition of
      BASRI-hips into BASRI-total (2-16). Cervical and lumbar spine were also scored in
      detail (SASSS, 0-36 each) and were combined into SASSS-total or "modified" SASSS
      (both range 0-72). To assess change a smallest detectable difference (SDD) was
      estimated for data on a quasi-interval scale. RESULTS: The SI scoring methods
      showed intra and interobserver kappa between 0.36 and 0.70. The BASRI-hip reached
      kappa between 0.59 and 0.84. Combined SASSS scores were most reliable, with intra
      and interobserver intraclass correlation coefficients (ICC) between 0.90 and
      0.96. The ICC of the combined BASRI scores were also very good, ranging from 0.85
      to 0.95. For SI New York, SI SASSS, and BASRI-hip, 0.3-1.2% of patients
      deteriorated 1 grade; 7.5% deteriorated 1 grade (6.3% of maximum score) in BASRI
      spine and BASRI-total, and observers agreed in up to 48% of the cases that no
      change occurred. The SDD was lowest (7.5; 10% of maximum score) for "modified"
      SASSS. Only 0.8% of patients deteriorated more than the SDD and observers agreed
      in up to 92% of the cases that no change occurred. CONCLUSION: Radiological
      scoring methods for AS are moderately to excellently reliable. Under the selected
      scoring conditions (concealed time order, average of 2 observers, SDD based on
      interobserver data, unselected patient population) there was too little change
      over 2 years to be detected reliably by the scoring methods.

PMID- 14705232
TI  - Behcet's disease in patients of German and Turkish origin living in Germany: a
      comparative analysis.
AB  - OBJECTIVE: To evaluate the relationship between ethnic origin and manifestations
      of Behcet's disease (BD) in patients of German and Turkish origin living in
      Germany. METHODS: Between 1995 and 2000, 32 patients of German and 33 patients of
      Turkish origin living in Germany were evaluated for the entire spectrum of
      disease manifestations, disease severity, HLA associations, sex, age at disease
      manifestation, and time to diagnosis. RESULTS: There were no statistically
      significant differences between German and Turkish patients. There was no
      association of sex or HLA-B51 with any manifestation of BD. The only significant
      difference between the 2 groups was the median time from the first manifestation
      of the disease to diagnosis, which was 0 years for the Turkish, but 3.5 years for
      the German patients (p = 0.0005). Additionally, 4 patients of German origin had
      been misdiagnosed as having spondyloarthropathy (SpA) before the final diagnosis
      of BD was made (12%). In comparison to Turkish patients living in Turkey (data
      from the literature), only 2 differences were found: one concerned the frequency
      of ocular involvement (lower in the patients in Turkey), and the other the male
      to female ratio, which was reported as 1.03:1 in Turkey, but 3.7:1 in Germany.
      CONCLUSION: Our results do not favor an ethnic influence on the expression of BD.
      Environmental influences may be responsible for the higher frequency of ocular
      manifestations and the higher male to female ratio in patients living in Germany
      compared to those living in Turkey.

PMID- 14705233
TI  - The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to
      standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis.
AB  - OBJECTIVE: To determine whether or not N of 1 trials with diclofenac/misoprostol
      (Arthrotec) are superior and cost-effective compared with standard treatment in
      osteoarthritis (OA). METHODS: We randomized subjects with OA who were "uncertain
      that nonsteroidal antiinflammatory drugs (NSAID) were helpful" to 2 different
      groups. One group received conventional treatment whereby they were told to stop
      their NSAID and to wait and see what happened. If necessary, treatment with other
      NSAID and all other usual OA treatment strategies were used. The other group
      received a series of crossover trials with diclofenac 50 mg and misoprostol 200
      micro g twice a day or an identical placebo for 2 weeks each in a random double
      blinded manner. Every 4 weeks they chose which treatment they preferred. By 3
      months, if there was no clear preference, the N of 1 trials were discontinued.
      All trial participants were seen monthly for 3 months and at 6 months. All costs
      (direct and indirect) were collected for both groups. Costs of research-generated
      visits were not counted in the "conventional treatment" group. RESULTS: Fifty-one
      subjects were randomized (stratified by most symptomatic OA area): 25 with knee,
      7 with hip, and 19 with hand OA. Twenty-four were randomized into the N of 1
      group. There were no differences in the baseline and followup variables including
      age, income, education, past and current NSAID use, global assessment, Health
      Assessment Questionnaire (HAQ), Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), and Medical Outcome Study Short Form-36 (SF-36)
      scores. In the N of 1 group, 11 patients preferred diclofenac in total (of whom 7
      did only one round, 2 did 2 rounds, and 2 did 3 rounds). None of the N of 1
      patients preferred placebo and 11 had no preference (2 dropped out at baseline).
      At 6 months, 15 of 19 in "conventional therapy" and 17 of 21 in N of 1 were
      taking NSAID. That is, NSAID appeared to be effective in 81% of N of 1 subjects
      and 79% of conventionally treated patients, even though subjects were initially
      uncertain that their NSAID were helpful. The total OA-related costs in Canadian
      dollars per patient (in 1996) for N of 1 treated patients at 6 months were:
      551.66 dollars +/- 154.02 dollars (SD) versus 395.62 dollars +/- 226.87 dollars
      for controls, excluding 2 research visits for controls (p < 0.009). The HAQ pain
      and disability, WOMAC scales, and physician global assessments improved more in
      the N of 1 group (at greater cost), but no between-group differences in efficacy
      were seen, possibly due to small numbers. CONCLUSION: N of 1 trials were time
      consuming in these patients and are more expensive, but with slightly better
      outcomes. In addition, NSAID seem to be effective in a majority of subjects with
      OA who have been uncertain of their benefit.

PMID- 14705234
TI  - Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on
      therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal
      antiinflammatory drug: a multicenter, randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of tramadol 37.5 mg/acetaminophen
      325 mg combination tablets (tramadol/APAP) as add-on therapy for subjects with
      osteoarthritis (OA) pain inadequately controlled by COX-2 nonsteroidal
      antiinflammatory drugs (NSAID). METHODS: This 91-day, multicenter, randomized,
      double-blind, placebo-controlled trial enrolled subjects with symptomatic OA for
      >/= 1 year who experienced at least moderate pain [visual analog scale (VAS)
      score >/= 50/100 mm] despite treatment with stable doses of celecoxib (>/= 200
      mg/day) or rofecoxib (>/= 25 mg/day). Tramadol/APAP or matching placebo was
      titrated to 4 tablets/day on Day 10 and thereafter as needed up to 8 tablets/day.
      The primary efficacy measure was final VAS score; secondary measures included
      final pain relief rating scores, subject/investigator overall medication
      assessments, rate and time to discontinuation due to lack of efficacy, and
      selected quality-of-life/physical functioning scores. RESULTS: Of 307 subjects
      randomized, 306 taking celecoxib (56.5%) or rofecoxib (43.5%) were included in
      the intent-to-treat population (n = 153 tramadol/APAP, 153 placebo). Mean final
      VAS scores for tramadol/APAP plus COX-2 NSAID were significantly lower than
      placebo plus COX-2 NSAID (41.5 vs 48.3; p = 0.025) and mean final pain relief
      rating scores were significantly higher (p = 0.002). Subjects taking
      tramadol/APAP showed significant improvements compared with placebo in
      subject/investigator medication assessments, as well as in the WOMAC Physical
      Function and the Medical Outcome Study Short Form-36 Role-Physical measures. The
      most common treatment-related adverse events for tramadol/APAP were somnolence
      (6.5%), nausea (4.6%), and constipation (3.3%). Mean tramadol/APAP dose was 4.1
      tablets (154 mg tramadol/ 1332 mg APAP). CONCLUSION: Tramadol 37.5 mg/APAP 325 mg
      combination tablets were effective and safe as add-on therapy with COX-2 NSAID
      for treatment of OA pain.

PMID- 14705235
TI  - Risk factors for knee osteoarthritis in Japanese women: heavy weight, previous
      joint injuries, and occupational activities.
AB  - OBJECTIVE: Risk of knee osteoarthritis (OA) associated with constitutional
      factors, history of joint injuries, and occupational factors was assessed in a
      case-control study among women in Japan. Results were contrasted with a
      comparable study in Britain. METHODS: The study covered 3 health districts in
      Japan. Cases were women aged >/= 45 years old, diagnosed with knee OA by
      orthopedic physicians utilizing radiography. No cases displayed established
      causes of secondary OA. Controls selected randomly from the general population
      were individually matched to each case for age, sex, and residential district.
      Subjects were interviewed using structured questionnaires to determine medical
      history, including history of joint injury, physical activity, socioeconomic
      factors, and occupation. Height and weight were measured. RESULTS: Interviews
      were obtained from 101 female cases and controls. The highest third of heaviest
      body weight in the past [high (> 62.0 kg) vs low (< 55 kg) odds ratio = 4.42, 95%
      confidence interval 1.17-16.64], previous injury to the knee (OR 7.11, 95% CI
      2.40-21.09), sedentary work during initial employment (OR 0.35, 95% CI 0.15
      0.84), and total working years (OR 1.05, 95% CI 1.01-1.08) represented
      independent factors associated with knee OA, after controlling for other
      potential risk factors. CONCLUSION: Heavy weight in the past appears to represent
      a risk factor for knee OA among women in Japan, as reported in Britain.
      Constitutional factors may represent important determinants for knee OA,
      regardless of race. Previous injury to the knee and occupational factors are also
      associated with knee OA in both Britain and Japan, although characteristic
      activities for work vary.

PMID- 14705236
TI  - Etidronate prevents high dose glucocorticoid induced bone loss in premenopausal
      individuals with systemic autoimmune diseases.
AB  - OBJECTIVE: To assess the efficacy of etidronate and alfacalcidol in preventing
      glucocorticoid induced bone loss in premenopausal women and men starting high
      dose glucocorticoid therapy. METHODS: Premenopausal women (n = 16) and men (n =
      5) who had just developed autoimmune diseases, and who agreed to use high dose
      glucocorticoid therapy for the first time, were randomized to receive
      alfacalcidol (1 micro g/day) alone (alfacalcidol group, n = 11); or alfacalcidol
      (1 micro g/day) and intermittent cyclical etidronate (200 mg/day for 14 days),
      given for 4 cycles (combined group, n = 10). They were treated with these
      medications as well as high dose glucocorticoids for 12 months. RESULTS: In the
      alfacalcidol group the percentage changes in bone mineral density (BMD) of the
      lumbar spine after 6 and 12 mo of therapy were -9.6 +/- 0.6% and -10.3 +/- 1.0%,
      respectively. However, in the combined group the percentage changes in lumbar
      spine BMD after 6 and 12 mo were -3.8 +/- 1.3% and -4.5 +/- 2.1%. The percentage
      lumbar spine bone loss rate in the combined group was significantly lower than in
      the alfacalcidol group at both 6 and 12 mo. After 12 mo the percentage change in
      femoral neck BMD was increased 2.3 +/- 1.5% in the combined group and was
      decreased 2.5 +/- 2.4% in the alfacalcidol group; this difference was also
      statistically significant. There were no significant differences in metabolic
      bone markers between the groups during the study. CONCLUSION: The results suggest
      that etidronate could prevent high dose glucocorticoid induced bone loss in
      premenopausal individuals with systemic autoimmune diseases.

PMID- 14705237
TI  - Hydrocortisone and deflazacort induce different effects on vitamin D receptor
      level increase produced by 1,25-dihydroxyvitamin D3 in rat osteoblast-like UMR
      106 cells.
AB  - OBJECTIVE: The homologous upregulation produced by 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] on vitamin D receptor (VDR) levels, and the effects produced by the
      heterologous agents hydrocortisone or deflazacort, alone or in conjunction with
      this vitamin D metabolite, were studied in rat osteoblastic UMR-106 osteosarcoma
      cells. METHODS: VDR were determined by binding analysis (Bmax and dissociation
      constant). VDR mRNA expression levels were measured by Northern blot analysis.
      RESULTS: Incubation with 10 nM 1,25(OH)2D3 produced a significant increase in
      Bmax with respect to ethanol-treated cells (100.2 +/- 13.2 vs 11.4 +/- 4.8 fmol
      3H-1,25(OH)2D3 bound/mg protein) together with a significant increase in VDR mRNA
      expression (483 +/- 170% vs 100%). The addition of 10 nM hydrocortisone to
      1,25(OH)2D3 produced a significant decrease in Bmax (from 100.2 +/- 13.2 to 44 +/
      5.6), with mRNA levels similar to those of basal conditions (116 +/- 25% vs
      100%). However, the addition of 10 nM deflazacort did not reduce the activation
      in Bmax produced by 1,25(OH)2D3 (92.4 +/- 16 vs 100.2 +/- 13.2), maintaining the
      increase in mRNA levels (430 +/- 10% vs 483 +/- 170%). If 10 nM hydrocortisone or
      10 nM deflazacort was added to UMR-106 cells without 1,25(OH)2D3, a similar
      increase was observed in Bmax with respect to basal conditions (20.4 +/- 1.3 or
      20.9 +/- 1.6 vs 11.4 +/- 4.8 in control cells), but hydrocortisone did not
      produce any significant variation in mRNA VDR levels, while deflazacort itself
      produced an increase in VDR mRNA expression. CONCLUSION: Our findings of
      different actions produced by hydrocortisone and deflazacort on the increase of
      VDR levels produced by 1,25(OH)2D3 could explain some of the different actions
      produced by both antiinflammatory medications on bone metabolism.

PMID- 14705238
TI  - Joint laxity and the benign joint hypermobility syndrome in student and
      professional ballet dancers.
AB  - OBJECTIVE: To ascertain the prevalence of hypermobility and the benign joint
      hypermobility syndrome (BJHS) in male and female student and professional ballet
      dancers, and explore whether BJHS has any effect on a dance career. METHODS:
      Students from the Royal Ballet School and professional dancers from the Royal
      Ballet Company, London, were compared with a control group of teenagers and
      adults from a local secondary school and The Royal Opera House, respectively. The
      data, examined by variance analysis, included anthropometric variables, the
      Beighton score, and clinical features constituting BJHS. Odds ratios for
      hypermobility and BJHS in dancers were calculated, and the prevalence and
      distribution of BJHS was examined. RESULTS: Hypermobility and BJHS were common in
      male and female dancers compared with controls. An OR of 11.0 (95% CI 3.3-31.8)
      was found for hypermobility in dancers for both the ballet school and the
      professional company. The prevalence of BJHS was found to decline both from
      student to professional and within the ballet company from corps de ballet to
      Principal. Odds ratios for BJHS in student dancers were significant, OR = 3.9
      (95% CI 1.3-11.3), but not so in professional dancers: OR = 1.7 (95% CI 0.6-4.7).
      Arthralgia was common in dancers and was reported more often in males than
      females. In females, pain was reported most by dancers with other features of
      BJHS, in particular stretchy skin. CONCLUSION: Hypermobility and BJHS are common
      in both male and female student and professional ballet dancers. The fall in
      prevalence, and the greater reporting of arthralgia with other features of BJHS
      in young female dancers, suggests that BJHS may have an important negative
      influence, and this may have implications for training. The same pattern was not
      observed in males, suggesting that their pain-reporting and injury are related to
      factors other than BJHS.

PMID- 14705239
TI  - The role of subcutaneous administration of methotrexate in children with juvenile
      idiopathic arthritis who have failed oral methotrexate.
AB  - OBJECTIVE: To describe the outcome of patients with juvenile idiopathic arthritis
      (JIA) treated with subcutaneous (Sc) methotrexate (MTX) after failing oral MTX
      (either because of inefficacy or toxicity) in a clinic population. METHODS: The
      study cohort was identified from our clinical database, and consisted of 61
      children with JIA treated with MTX between 1988-2001. All patients fulfilled
      International League Against Rheumatism (ILAR) criteria for JIA and had disease
      duration of >/= 6 months and 3 or more active joints before institution of MTX.
      All patients had a core set of outcome variables assessed at baseline and at 3
      months after achieving both maximum oral and SC MTX. Outcome variables included
      physician global assessment of disease activity, number of active joints, number
      of joints with limited range of motion, duration of early morning stiffness, and
      erythrocyte sedimentation rate (ESR). Improvement was defined as at least 30%
      improvement from baseline in 3 of 5 variables in the core set, with no more than
      one of the remaining variables worsening by more than 30%. RESULTS: A total of 61
      patients, 43 females and 18 males with JIA were studied. The disease subtypes
      were systemic 8, polyarticular 25 (12 rheumatoid factor positive), oligoarticular
      14, enthesitis related arthritis 5, and unclassified 4. Thirty-one patients were
      switched to SC MTX, 13 of whom had not improved, and 18 who had improved, but had
      nausea (11) or insufficient clinical improvement (7). After 3 months of SC MTX
      treatment, 76% of patients were classified as improved and 23% as not improved.
      Toxicity on SC MTX was less than on oral MTX. CONCLUSION: Our results suggest
      that for patients failing oral MTX either because of inefficacy or toxicity, the
      use of SC MTX has a high likelihood of success with more than 70% of patients
      achieving clinically significant improvement, without clinically significant
      toxicity.

PMID- 14705240
TI  - Autoimmune response in mothers of children with congenital and postnatally
      diagnosed isolated heart block: a population based study.
AB  - OBJECTIVE: To study the autoimmune response in mothers of children with isolated
      congenital heart block (CHB) and heart block (HB) diagnosed postnatally. METHODS:
      We reviewed the Finnish hospital registries for patients born between 1950 and
      2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and
      sera for the determination of autoantibodies were available from 67 mothers of
      children with CHB and from 37 mothers of children with postnatally diagnosed HB
      9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal
      antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time
      resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker
      antibodies for connective tissue diseases (CTD) were determined by immunoblot
      and/or by immunofluorescence. The control group comprised 136 mothers with
      primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD
      with healthy children. RESULTS: Sixty of our 67 mothers (90%) of children with
      CHB had antibodies to SSA or SSB by the methods initially used in this study.
      When retests and tests performed previously were taken into account, only 3 (4%)
      of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had
      antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone
      proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%)
      had any autoantibodies. Increased risk of having a child with CHB was indicated
      by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays,
      whereas low risk was indicated by maternal SLE or other CTD and undetectable or
      low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly
      superior to others, but in general, immunoblots were more specific than TR-FIA.
      CONCLUSION: Maternal autoimmune disorder is almost always associated with CHB but
      only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker
      antibodies for mothers of children with CHB, and an increased risk of having an
      affected child is indicated by maternal primary SS and high titer antibodies to
      SSA and SSB.

PMID- 14705241
TI  - Diabetic muscle infarction: case report and review.

PMID- 14705242
TI  - Economic cost and epidemiological characteristics of fibromyalgia.

PMID- 14705244
TI  - Dukes' staging is poorly understood by doctors managing colorectal cancer.

PMID- 14705243
TI  - An unusually complicated case of primary Sjogren's syndrome: development of
      transient "lupus-type" autoantibodies following silicone implant rejection.

PMID- 14705246
TI  - [Emergency services. A new plan for preventing a crisis].

PMID- 14705247
TI  - [America ... I want to see it...].

PMID- 14705248
TI  - [Health status of children 5-6 years old: regional disparities].

PMID- 14705249
TI  - [Urinary incontinence in women].

PMID- 14705250
TI  - [Smoking: finished with dependence].

PMID- 14705251
TI  - [Dreaming your life away. Or managing a relationship with a comatose patient in
      intensive care].

PMID- 14705252
TI  - [Nurse's role in the multidisciplinary consultation for pain].

PMID- 14705253
TI  - [A history of fairies in the hospital].

PMID- 14705254
TI  - [A sick person even in his weakened situation still has rights. Interview by
      Marie-France Guerel].

PMID- 14705255
TI  - [Self monitoring and management of hypertension].

PMID- 14705256
TI  - [Adefovir].

PMID- 14705257
TI  - [Hospitalization of mentally ill persons. II -- Office hospitalization].

PMID- 14705259
TI  - [Primary care in an isolated region: a question of survival].

PMID- 14705260
TI  - Healthy life expectancy: comparison of OECD countries in 2001.
AB  - OBJECTIVES: To compare average levels of population health for Australia and
      other OECD countries in 2001. METHODS: Healthy life expectancies (HALE) for OECD
      countries for 2001 are based on analysis of mortality data for OECD countries,
      country-specific estimates of health state prevalences for 135 causes from the
      Global Burden of Disease 2000 study, and an analysis of 34 health surveys in 28
      OECD countries, using novel methods to improve the comparability of self-report
      data. RESULTS: HALE at birth ranges from a low of 59.8 years for Turkey to a high
      of 73.6 years in Japan in 2001. Australia ranks fourth among OECD countries at
      71.6 years with a 95% uncertainty interval of 70.9 to 72.8 years, ahead of New
      Zealand in 13th place at 70.3 years. The equivalent 'lost' healthy years at birth
      range from around 10 years in OECD countries with lowest life expectancies to
      around eight years in those with high life expectancies at birth. There is a
      statistically significant association between higher levels of health expenditure
      and higher healthy life expectancy across OECD countries, although causal
      inferences require more sophisticated analyses of the health system and non
      health system determinants of levels of health. CONCLUSIONS: The new methods used
      in the WHO Multi-Country Household Survey Study have increased the comparability
      of self-report data across OECD countries, a major step forward in the use of
      self-reported data on health. Building on this experience, WHO is developing
      improved health status measurement techniques for a World Health Survey to be
      carried out in 2002/03.

PMID- 14705261
TI  - Refugee intake: reflections on inequality.
AB  - BACKGROUND: Refugees represent one of the most marginalized populations with
      generally poor health outcomes and requirements often very different from, and in
      excess of, the populations in the countries of asylum. It stands to reason that
      countries that accept refugees should have the resources to support them.
      Although governments in industrialised countries are often vociferous about the
      generosity of their support for refugees, the appearance is that it is the
      poorest nations that bear the greatest burden. This has important implications
      for the allocation of resources to support the health and welfare needs of
      refugees. The distribution of refugees globally and the wealth of the countries
      of asylum are examined in this paper. METHOD: Data on the numbers of refugees
      accepted in each country were obtained from the United Nations High Commissioner
      for Refugees. These were used to analyse the 'fairness' of the distribution of
      refugees according to the economic capacity of the host countries. FINDINGS: A
      similar distribution of refugees prevails in the poorest quintile of countries
      and in the richest. Although there is considerable between-country variation,
      when account is taken of economic capacity, the poorest countries bear the
      greatest burden. INTERPRETATION: The distribution of refugees is in stark
      contrast to the humanitarian rhetoric of the industrialized countries. The
      implications of the inequitable distribution on health cannot be overemphasized.

PMID- 14705262
TI  - Health of mothers with intellectual limitations.
AB  - OBJECTIVE: To investigate the health status of mothers with intellectual
      limitations. METHOD: The health status of 50 mothers with intellectual
      limitations in metropolitan Sydney was assessed during the baseline assessment
      phase of a randomised controlled trial of a parent education program. RESULTS:
      Self-reported maternal health was significantly worse than women's health in the
      Australian population. Controlling for socio-economic status, mothers' health
      remained significantly worse on four of the eight subscales. CONCLUSIONS: The
      findings suggest that mothers with intellectual limitations are particularly at
      risk for poor health status. An urgent need exists for policy and service
      initiatives to address the health status of this group of vulnerable mothers.

PMID- 14705263
TI  - Having a baby in Victoria 1989-2000: women's views of public and private models
      of care.
AB  - OBJECTIVE: To assess and contrast women's views of antenatal, intrapartum and
      postnatal care based on data collected in three state-wide surveys of recent
      mothers conducted in 1989, 1994 and 2000. METHODS: Postal surveys were mailed to
      all women who gave birth in Victoria in one week in 1989, and in two weeks in
      1993 and 1999, excluding those who had a stillbirth or neonatal death.
      Questionnaires were sent to women by hospitals and home birth practitioners 5-8
      months after the birth. RESULTS: 58.6% of women participating in the 1989 survey
      rated their antenatal care as 'very good' compared with 62.4% in 1994 and 66.5%
      in 2000 (chi 2 for trend = 15.01, p < 0.001). In all three surveys, women
      enrolled in public models of care were significantly more likely to rate their
      antenatal care as less than 'very good' than women enrolled in private models of
      care. More than two-thirds of the women in each survey rated their intrapartum
      care as 'very good' (1989-67%, 1994-71%, 2000-72%). Over the time period there
      was an improvement in the proportion of women rating their care as 'very good'
      among women in private care (chi 2 for trend = 33.1, p < 0.001), but no
      improvement was seen in public care. Only 52% (1994) and 51% (2000) of women
      rated their postnatal care as 'very good'. CONCLUSIONS: The conduct of three
      population-based surveys of recent mothers in Victoria over the past 10 years has
      provided valuable information for charting the impact of organisational changes
      on women's views and experiences of maternity care.

PMID- 14705264
TI  - Socio-economic differentials in the health-related quality of life of Australian
      children: results of a national study.
AB  - OBJECTIVE: To examine differences in health-related quality of life (HRQL) of
      children living in different socio-economic contexts in Australia. METHODS:
      Parental reports describing the HRQL and socio-economic status of a random
      national sample of 3,597 school-age children were obtained using the Child Health
      Questionnaire (CHQ) and a standardised socio-economic interview. Response rate
      was 70%. RESULTS: Children in families of higher income, whose parents had more
      years of schooling and were employed and children who lived in two-parent,
      original families had significantly higher HRQL across a range of domains
      assessed by the CHQ. CONCLUSION: Children from lower socio-economic backgrounds
      in Australia have a significantly more negative experience of health and
      wellness. Such differences may well increase unless deliberate political
      attention is given to addressing the widening differences in relative wealth in
      Australia.

PMID- 14705265
TI  - The benefits and costs of tamoxifen for breast cancer prevention.
AB  - OBJECTIVE: To estimate the effects of key uncertainties on the effectiveness and
      cost-effectiveness of breast cancer prevention with tamoxifen. METHODS: The
      incremental cost-effectiveness ratio of tamoxifen therapy relative to placebo was
      estimated using decision analysis with Markov modelling of health states,
      outcomes and costs for a simulated cohort of women at high risk for breast
      cancer. Relative effects of tamoxifen's benefits and harms were estimated from
      meta-analyses of randomised controlled trials. Cost estimates were based on
      Australian treatment patterns and costs. The main outcome measure was cost per
      quality-adjusted life year (QALY) gained with costs and effects discounted at a
      5% annual rate. RESULTS: Tamoxifen therapy over five years reduces the incidence
      of breast cancer by approximately 1.4%, which is offset by an increase in
      endometrial cancer of 0.7% and pulmonary embolism of 0.2%. If the reduction is
      permanent (preventing new breast cancers emerging over five years and no further
      treatment effect thereafter), the model estimates an increase in life expectancy
      of 0.057 QALYs and an extra cost of $2,193; or $38,271/QALY gained. A model
      assuming further treatment effects of tamoxifen preventing new breast cancers
      emerging for up to 10 years results in an incremental cost of $19,354/QALY.
      However, if five years of tamoxifen therapy merely delays when these breast
      cancers appear (such that by 10 years there is no longer a reduced incidence),
      the incremental cost per QALY saved is estimated to be $199,149. CONCLUSIONS:
      Tamoxifen is potentially cost-effective in preventing breast cancer in women at
      high risk. However, its cost-effectiveness as a preventive therapy is highly
      sensitive to whether these cancers are permanently prevented or their clinical
      presentation is only delayed. Long-term follow-up in randomised controlled trials
      is therefore crucial in forming health policy.

PMID- 14705266
TI  - Quality of life and colorectal cancer: a review.
AB  - OBJECTIVES: To describe what is known of quality of life for colorectal cancer
      patients, to review what has been done in the Australian setting and to identify
      emerging directions for future research to address current gaps in knowledge.
      METHOD: A literature search (using Medline, Psychinfo, CINAHL and Sociological
      Abstracts) was conducted and 41 articles identified for review. RESULTS: Three
      key areas relating to quality of life in colorectal cancer patients emerged from
      the literature review: the definition and measurement of quality of life;
      predictors of quality of life; and the relationship of quality of life to
      survival. Results of existing studies are inconsistent in relation to quality of
      life over time and its relationship to survival. Small sample sizes and
      methodological limitations make interpretation difficult. CONCLUSIONS: There is a
      need for large-scale, longitudinal, population-based studies describing the
      quality of life experienced by colorectal cancer patients and its determinants.
      Measurement and simultaneous adjustment for potential confounding factors would
      productively advance knowledge in this area, as would an analysis of the economic
      cost of morbidity to the community and an assessment of the cost effectiveness of
      proposed interventions. IMPLICATIONS: As the Australian population ages, the
      prevalence of colorectal cancer within the community will increase. This burden
      of disease presents as a priority area for public health research. An improved
      understanding of quality of life and its predictors will inform the development
      and design of supportive interventions for those affected by the disease.

PMID- 14705267
TI  - The four Ds deconstructed.
AB  - For decades, pamphlets provided by credible government authorities have
      reproduced tips for quitting smoking, recommended with certainly, but with no
      basis in facts, findings or substantiated outcomes. The 'four Ds' are an example
      of a universally accepted set of instructions to quit smoking that has little
      basis in science. This anomaly is at odds with the era of evidence-based medical
      interventions and should be addressed.

PMID- 14705268
TI  - Validation of self-reported cigarette smoking in a remote Australian Aboriginal
      community.
AB  - OBJECTIVE: To examine the relationship between self-reported tobacco smoking and
      urinary cotinine concentrations in the setting of a remote Aboriginal community.
      METHODS: In a remote Northern Territory (NT) Aboriginal community the
      relationship between self-reported tobacco smoking and urinary cotinine
      concentrations was examined as part of a cross-sectional survey of cardiovascular
      risk factors. Current tobacco smoking was assessed as part of a questionnaire.
      The concentration of cotinine and cotinine/creatinine ratio (CCR) in a spot urine
      sample were used as a biochemical marker of nicotine exposure. RESULTS: A total
      of 237 people took part in the survey, although completed questionnaires and
      urine results were available for 184 people. Current tobacco smoking was reported
      by 161 (69 [95% CI 63 to 75]%) people, with higher rates among males (84/104, 81
      [95% CI 72 to 88]%) than females (77/129, 60 [95% CI 51 to 68]%, p < 0.001).
      There was good agreement of self report with current tobacco smoking using
      categories based on urinary cotinine (agreement 94%, kappa = 0.84) and urinary
      CCR (agreement 94%, kappa = 0.86). Quantitative agreement between cotinine
      measures and self-reported number of cigarettes per day was better for CCR than
      cotinine, but the correlation was relatively weak for both. CONCLUSIONS: Self
      reported cigarette smoking is a valid qualitative measure in this environment.
      The relatively weak correlation between the biomarker and number of reported
      cigarettes smoked illustrates problems both with questionnaire and urinary
      markers of nicotine exposure. IMPLICATIONS: As a qualitative measure of tobacco
      smoking in this setting, self-report appears adequate but the validity of
      quantitative self-report is unclear.

PMID- 14705269
TI  - A group intervention to reduce smoking in individuals with psychiatric disorder:
      brief report of a pilot study.
AB  - OBJECTIVES: To evaluate a group intervention to help individuals with psychiatric
      disorder stop smoking. METHOD: A waitlist-treatment crossover design. Outcome
      measures included smoking cessation, motivation to stop, the Fagerstrom Test for
      Nicotine Dependence (FTND), urinary cotinine and psychiatric symptoms on the
      General Health Questionnaire. RESULTS: 38 subjects participated, of whom 19
      completed the waitlist and intervention phases. There were no significant
      differences between subjects and dropouts. During the waitlist period there were
      no significant changes in tobacco use. At the end of the intervention, almost a
      quarter had stopped smoking, (z = -2.24, p = 0.02). Subjects also showed
      significant improvements on state of change, FTND score and urinary cotinine
      levels. These improvements were maintained at three-month follow-up (n = 10).
      Psychiatric morbidity showed no change. CONCLUSIONS: It is possible to reduce
      smoking in individuals with psychiatric disorder. IMPLICATIONS: Larger randomised
      controlled trials are indicated to determine the relative contributions of
      nicotine replacement, bupropion and group interventions to smoking cessation in
      this population.

PMID- 14705270
TI  - Evaluation of safety training for manual handling of people with disabilities in
      specialised group homes in Australia.
AB  - OBJECTIVE: This paper attempted to examine the question of whether 351 disability
      services workers in an Australian State Government agency given manual handling
      training had significantly lower injury rates from manual handling injuries a
      year post-training than a control group (n = 351) without the training. METHODS:
      Control group members were selected by stratified random sampling to closely
      match the intervention group. The measures employed were the number of reported
      manual handling injuries per 100 full-time equivalents by certain
      characteristics, frequency of incidents, mean workers' compensation cost, and
      mean compensated days. RESULTS: Training in manual handling methods significantly
      reduced the risk by as much as 42%, with an average rate of 49.6 per 100 full
      time equivalents (95% confidence interval 44.4-55.0) among the intervention group
      compared with 84.8 per 100 full-time equivalents (95% confidence interval 76.0
      94.1) among controls. The risk differential was consistent across gender, age
      group, length of service, and job classification. However, in two injury
      categories (client lift/transfer and general manual handling), the intervention
      group had a marginally higher risk. The average workers' compensation cost in the
      control group was 4.2 times that in the intervention group. CONCLUSION: While the
      study has some weaknesses, overall, there is little evidence to suggest that the
      outcome observed was due to threats to internal validity. It is expected that the
      findings can encourage further evaluation studies of workplace safety training
      programs.

PMID- 14705271
TI  - Influenza vaccination of staff in aged care facilities in the ACT: how can we
      improve the uptake of influenza vaccine?
AB  - OBJECTIVE: To examine the self-reported uptake of influenza vaccine by staff in
      residential aged care facilities in the Australian Capital Territory (ACT), and
      the factors influencing vaccine uptake by staff. METHODS: Two confidential cross
      sectional surveys were conducted in all (n = 19) residential aged care facilities
      in the ACT in June 2000. An interview with directors of each facility collected
      information on the institutional policy and practices for influenza vaccination.
      An anonymous postal survey of staff collected information on self-reported
      influenza vaccination status and staff awareness and attitudes to the
      vaccination. RESULTS: All directors were interviewed (n = 19) and 50% of staff
      questionnaires (n = 587) were completed. Of respondents, 28% reported receiving
      influenza vaccine for the 2000 influenza season. Uptake of the vaccine was
      associated with particular policies and practices of facilities such as:
      organisation of vaccination for staff (OR 2.52, CI 1.38-4.59, p < 0.001);
      provision of reminders to staff (OR 2.73, CI 1.70-4.06, p < 0.001); and provision
      of information on the need for vaccination (OR 1.94, CI 1.03-3.67, p < 0.001).
      Other factors significantly associated with influenza vaccine uptake included:
      previous uptake of the vaccine (OR 52.2, CI 35.2-77.4, p < 0.001), vaccination
      arranged by the workplace (OR 4.02, CI 2.66-6.07, p < 0.001), and awareness of
      recommendations for staff employed in aged care facilities (OR 3.66, CI 2.28
      5.85, p < 0.001). The main reasons given for not receiving the vaccine were the
      belief that it had significant side effects (42%, n = 146), and concerns about
      its effectiveness (32%, n = 109). CONCLUSIONS: This study identified a number of
      factors that can be incorporated into strategies and programs to improve uptake
      of influenza vaccine by staff in residential aged care facilities.

PMID- 14705272
TI  - Trends in physical activity participation and the impact of integrated campaigns
      among Australian adults, 1997-99.
AB  - OBJECTIVES: To determine whether awareness of the moderate physical activity
      message and prevalence of participation changed among Australian adults between
      1997 and 1999, and if changes differed across Australia. METHODS: Data were
      compared on awareness of the moderate physical activity message and on physical
      activity participation from identical national physical activity surveys in 1997
      and 1999. RESULTS: In 1999, following integrated public health efforts,
      recognition of the Active Australia campaign was substantially higher in NSW/ACT
      (61.7%) than elsewhere (29.3%). Knowledge about benefits of moderate activity
      increased between 1997 and 1999, more so in States with public health campaigns.
      National participation in 'sufficient physical activity' declined between 1997
      and 1999, from 63% to 57%, but the decline was smaller in NSW/ACT (4.4%) than in
      the other States (6.0%). CONCLUSIONS AND IMPLICATIONS: Declining trends in
      physical activity in Australia require increased public health investments,
      including strategic planning and public education, such as occurred in NSW
      (1997/98).

PMID- 14705273
TI  - Need for screening for genital Chlamydia trachomatis infection in Australia.
AB  - Genital Chlamydia trachomatis is the most common notifiable sexually
      transmissible infection in Australia and is associated with significant
      complications, particularly for women. There is no screening program for
      chlamydia in Australia despite this infection fulfilling the criteria for
      screening--it is easily diagnosed with acceptable self-administered tests and
      early treatment prevents complications. Screening for chlamydia reduces the
      prevalence of infection and the rate of complications and is recommended by
      several Western countries including the United States, England and Canada. If a
      screening program was introduced in Australia, several issues would first need to
      be addressed including who would be screened, how often would they be screened
      and where would screening be offered. We discuss these issues in this paper in an
      effort to advance the debate and the introduction of chlamydia screening in
      Australia.

PMID- 14705274
TI  - Illness in returned travellers presenting at GeoSentinel sites in New Zealand.
AB  - OBJECTIVE: To describe illnesses of returned travellers presenting at GeoSentinel
      sites in New Zealand. METHODS: Record data for all patients presenting for travel
      related illnesses seen at two GeoSentinel sites, operating as commercial travel
      clinics, in Auckland and Hamilton, NZ, were extracted for the period November
      1997 to December 2001. RESULTS: 205 patients were identified with 262 diagnoses.
      Just over half were females (54.21%) and nearly half were in the 25-35 years age
      group (47.3%). About two-fifths of patients reported a pre-travel health
      consultation (41.0%). The commonest diseases diagnosed were diarrhoeal illnesses
      (23%), dermatological diagnoses (16%, excluding animal bites), animal bites
      (10%), and non-specific viral illnesses (8%), many of which manifest as
      respiratory infections. Tropical diseases, such as schistosomiasis (4%) malaria
      (2%) and dengue fever (0.5%), were not common. CONCLUSIONS: Information on travel
      related illnesses, when reported through a global reporting system, can be useful
      for the travel health adviser in identifying issues of current concern. Although
      the frequency of tropical disease is low, it remains important to prevent these
      potentially fatal diseases. IMPLICATIONS: GeoSentinel makes a global contribution
      to the surveillance of emerging and re-emerging infectious diseases through a
      network of individual sites in various countries including New Zealand. This
      information can be used to help provide preventive advice for travellers as well
      as help in assessing illness in post-travel patients and potentially assist in
      preventing the secondary spread of some diseases acquired abroad following
      return.

PMID- 14705275
TI  - Skin surgery on Australian children, adolescents and young adults. Why so much?

PMID- 14705276
TI  - Who does not know that tobacco causes 80% of drug-related deaths?

PMID- 14705277
TI  - Regulation: proactive or reactive?

PMID- 14705278
TI  - Is home screening for bowel cancer a good idea?

PMID- 14705279
TI  - Inequity in Australian health care: how do we progress from here?
AB  - OBJECTIVE: To determine some of the key problems in pursuing equity in Australian
      health care and to identify some of the ways of overcoming these problems,
      particularly in Aboriginal and Torres Strait Islander health care. METHODS: To
      identify and debate the key equity issues particularly related to Aboriginal and
      Torres Strait Islander health care but also with respect to public versus private
      and rural/remote versus metropolitan. RESULTS: Political leadership and political
      will plus a more compassionate, less complacent society are crucial. CONCLUSIONS
      AND IMPLICATIONS: Political leadership is needed that can inspire a more
      compassionate society and which reflects better the informed values of the
      Australian people, adopting a communitarian paradigm. There is a need for a
      'health care constitutional convention' to allow the values of the populace with
      respect to equity to be elicited and to ensure that voices of the disadvantaged
      are heard. In the specific context of Aboriginal and Torres Strait Islander
      health care, there is a need first to recognise and thereafter break down the
      racism that exists in many Australian institutions.

PMID- 14705280
TI  - Big yellow taxi, or, unhealthy terms of trade?
AB  - International trade agreements, including the General Agreement on Trade in
      Services, are central elements of globalization. These agreements are likely to
      have significant implications for population health in rich nations such as
      Australia as well as in the developing world. But the technical language of the
      legal agreements and the comparative secrecy of the negotiations and approval
      procedures make it difficult for most people to be adequately informed about
      them. Australian public health academics and practitioners must become better
      informed and more pro-active in their approach to 'free trade' if Australia's
      public health infrastructure is to be protected from potential legal erosion.

PMID- 14705281
TI  - Randomised trial of intensive academic detailing to promote opportunistic
      recruitment of women to cervical screening by general practitioners.
AB  - OBJECTIVE: To evaluate a multifaceted intervention involving intensive academic
      detailing for general practitioners (GPs) to improve recruitment of women for
      cervical screening. METHODS: We conducted a cluster randomisation trial involving
      39 general practices in inner-metropolitan Sydney. GPs' knowledge, propensity to
      an opportunistic approach, competence and confidence were assessed by self-report
      before and after the intervention. To measure GP behaviour, recall of an
      opportunistic discussion about cervical screening was determined in cross
      sectional samples of female patients at baseline (n = 1,090) and post-test (n =
      1,062). RESULTS: Knowledge improved marginally in both groups but there were no
      changes in other GP self-reported measures. At post-test, women attending GPs in
      the intervention group were no more likely than those in the control group to
      recall an opportunistic inquiry about their cervical screening status (OR 0.65,
      95% CI 0.40-1.08). Women in the intervention group who were overdue for cervical
      screening were no more likely than their control group counterparts at post-test
      to recall advice about cervical screening (OR 2.16, 95% CI 0.75-6.14) or written
      information (OR 0.34, 95% CI 0.04-26.5). CONCLUSIONS: Intensive academic
      detailing does not improve an opportunistic approach to cervical screening in
      general practice. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: In an evidence-based
      climate, implementation of academic detailing as a strategy to improve cervical
      screening rates in general practice would be premature.

PMID- 14705282
TI  - Trusting technology: women aged 40-49 years participating in screening for breast
      cancer--an exploratory study.
AB  - OBJECTIVE: This paper reports key findings from an exploratory study of factors
      associated with women's decision to participate in mass mammography screening in
      Tasmania. In particular, we explored factors that contribute to the choice to
      participate in screening by women who are outside the primary target group, and
      for whom the evidence of benefit remains contentious. METHODS: Semi-structured
      interviews were conducted with a small sample of women aged between 40 and 49
      years in rural Tasmania who had participated in mammography screening. RESULTS:
      Key ideas that appeared to shape participation included the fear of breast
      cancer, trust in technology, and taking responsibility for health. Information
      provision is also an important factor in shaping participation patterns.
      CONCLUSIONS AND IMPLICATIONS: In order to facilitate informed consent,
      information provision in this area should take account of the dominant ideas that
      shape the decision to participate in breast cancer screening.

PMID- 14705283
TI  - Influence of 'framing effect' on women's support for government funding of breast
      cancer screening.
AB  - OBJECTIVES: To explore whether Australian women's support for government funding
      of mammographic screening is influenced by 'framing effect'. METHOD: Self
      administered survey of 701 women in general practice to elicit their support for
      government funding of each of four mammographic screening programs where benefits
      were expressed as a relative risk reduction (RRR); absolute risk reduction (ARR);
      number needed to screen (NNS) and number of cases detected for additional death
      avoided. RESULTS: The proportion of respondents indicating they 'definitely would
      support funding' was significantly greater when benefits were expressed as RRR
      than ARR (chi 2(1) = 148.4, p < 0.0001), NNS (chi 2(1) = 126.4, p < 0.0001) or
      number of cases detected for additional deaths avoided (chi 2(1) = 29.0, p <
      0.0001). 55.8% of women were not influenced by 'framing effect'. Younger women
      and those with higher educational levels were more likely to be susceptible to
      'framing effect'. CONCLUSION: Having demonstrated its influence among these
      women, 'framing effect' should be acknowledged in future research.

PMID- 14705284
TI  - The word 'cancer': reframing the context to reduce anxiety arousal.
AB  - This study investigated reaction to the word 'cancer' versus the phrase 'a
      cancer' in two ways: (1) assessing associations to the spoken words 'cancer' or
      'a cancer'; and (2) presenting participants with a situation where one person
      says to another in print. 'I have cancer' or 'I have a cancer'. The participants
      were a convenience sample of 112 adults (i.e. aged 18 years or over), 55 males
      and 57 females, recruited via a mall intercept survey in the Perth (Western
      Australia) central business district. Participants were randomly assigned to
      either the 'cancer' condition or the 'a cancer' condition. Both methods confirmed
      that cancer arouses primarily negative affective responses in the vast majority
      of people. It was hypothesised that using 'a cancer' might lead to less negative
      affect associations than just the word 'cancer'. This was found to be the case
      for the spoken word association technique, but not for the printed cartoon
      technique.

PMID- 14705285
TI  - A review of tobacco interventions for Indigenous Australians.
AB  - OBJECTIVE: To conduct a review of interventions to reduce the harm resulting from
      tobacco use among Indigenous Australians and to discuss the likely effect of a
      range of tobacco interventions if conducted in this population. METHODS: A
      systematic review of medical literature and an audit of information from 32
      government departments, non-government organisations and indigenous health
      organisations, which was completed in March 2001. RESULTS: A number of small
      tobacco programs had been conducted. Only four tobacco interventions had been
      evaluated in indigenous communities: a trial of training health professionals in
      conducting a brief intervention for smoking cessation; a trial of a CD-ROM on
      tobacco for use with indigenous schoolchildren; a qualitative evaluation of the
      effect of a mainstream advertising campaign on Indigenous people; and a pilot
      study of smoke-free workplaces, evaluated by qualitative methods. None of these
      studies assessed smoking cessation as an outcome. Two of these studies were
      unable to conclusively show any effect of the interventions; training health
      professionals in delivering a brief intervention resulted in some changes to
      practice and the evaluation of the mainstream advertising campaign showed that
      following the campaign, knowledge about tobacco had increased. CONCLUSIONS: There
      was a major lack of research on and evaluation of tobacco interventions for
      Indigenous Australians. IMPLICATIONS: More research and evaluation is required to
      ensure that tobacco interventions are appropriate and effective for Indigenous
      people. It is time to cease chronicling the ill health of Indigenous Australians
      and time to ensure the availability of well-evaluated, effective tobacco
      programs.

PMID- 14705286
TI  - Effectiveness of smoking cessation interventions: review of evidence and
      implications for best practice in Australian health care settings.
AB  - OBJECTIVE: To review the evidence of the effectiveness of various smoking
      cessation methods and appropriateness for use in Australian health care settings.
      METHODS: Cochrane and other existing reviews and meta-analyses of evidence were
      the basis for the review. Systematic literature searches were also conducted to
      identify relevant controlled trials published internationally between January
      1999 and May 2002. The main inclusion criteria for studies were use of a
      controlled evaluation design and an outcome measure of continuous abstinence from
      smoking for at least five months. A three-tiered grading system for strength of
      evidence was used. RESULTS: Clinic and hospital systems to assess and document
      tobacco use and routine provision of cessation advice can double long-term quit
      rates. While brief intervention can achieve a significant effect at population
      level, at individual level there is a strong dose response between the number and
      length of sessions of tobacco cessation counselling and its effectiveness.
      Effective behavioural interventions can increase cessation rates by 50-100%
      compared with no intervention. Some pharmacotherapies are safe and also help to
      substantially increase cessation rates. CONCLUSIONS: Effective behavioural and
      pharmacological methods of tobacco cessation are available. IMPLICATIONS: Every
      smoker should be offered evidence-based advice and treatment to quit smoking.
      This includes pharmacotherapy, unless contra-indicated. Health professionals and
      health care settings can play a significant role in motivating and assisting
      smokers to quit.

PMID- 14705287
TI  - Support for smoking restrictions in bars and gaming areas: review of Australian
      studies.
AB  - OBJECTIVE: To document levels of public support in Australia for smoking
      restrictions in licensed premises, including trends over time, and to examine the
      potential effects of a ban on patronage. METHOD: Systematic review of published
      and unpublished studies of community and staff attitudes towards smoking in bars,
      gaming areas and related venues were identified using Medline, Current Contents,
      PsycINFO and AUSTHealth prior to September 2002. State and Territory health
      departments, cancer organisations and branches of the National Heart Foundation
      were approached. Cross-sectional surveys reporting data on attitudes towards
      smoking restrictions and/or perceptions of effects on patronage were sought. Two
      reviewers assessed studies for inclusion. One extracted data using pre-coded
      categories with checking by the second. RESULTS: Thirty-four community and seven
      staff surveys were synthesised qualitatively, with greater emphasis given to
      surveys using random selection. All surveys conducted since 1993, which included
      the separate smoking area response option, have demonstrated majority support for
      some form of smoking restriction on licensed premises. From 2000, surveys with
      the ban option alone report majority support for prohibiting smoking completely
      in bars (52-68%) and gaming areas (64-76%). Support increased significantly after
      the Sharp damages award. Customer preference data indicate banning smoking is
      most likely to have a neutral or positive effect on patronage. CONCLUSIONS AND
      IMPLICATIONS: Support for a ban on smoking in licensed premises has increased by
      almost 20% in the past decade. State and Territory governments should introduce
      legislation banning smoking in all indoor drinking and gaming areas immediately.

PMID- 14705288
TI  - A cohort study of drink-driving motor vehicle crashes and alcohol-related
      diseases.
AB  - OBJECTIVES: To elicit whether drivers involved in alcohol-related motor vehicle
      crashes are more likely to have future alcohol-related hospital admissions.
      METHOD: A population-based cohort study of 3,286 drivers involved in a motor
      vehicle crash between 1988 and 1992 were followed over an eight to 13-year
      period. RESULTS: The findings from the study suggest a twofold increased risk
      associated with an alcohol-related motor vehicle crash and future alcohol-related
      hospital admission. The average time between an alcohol-related motor vehicle
      crash and future alcohol-related hospital admission was 12 years. Men and
      indigenous Australian drivers were more likely to have a future alcohol-related
      hospital admission. CONCLUSION: It is evident from this study that drink-driving
      resulting in a motor vehicle crash and hospitalisation could be considered an
      indicator of a less overt problem of alcohol dependency. IMPLICATIONS: It is
      important that penalties for drink-driving go beyond merely punitive action and
      provide rehabilitation.

PMID- 14705289
TI  - Agricultural motorcycle injuries in WA adolescents.
AB  - OBJECTIVE: To determine and compare the prevalence, nature and predictors of
      agricultural motorcycle injuries (2, 3 & 4 wheels) in a high-risk cohort of
      Western Australian adolescents. METHODS: A cross-sectional survey of 326 students
      (Years 11 and 12) was drawn from the six designated agricultural colleges, in
      Western Australia. The survey instrument was assessed as reliable and measured
      riding exposure, vehicle type and maintenance, use of protective equipment,
      training and injury experience. RESULTS: For those subjects with access to an
      agricultural motorcycle (n = 240), a total of 53% (n = 127) had incurred an
      injury. Of these, 73% (n = 92) resulted from two wheelers and 24% (n = 31) from
      ATVs, with 3% (n = 4) not specified. No significant differences in the nature of
      injury or body parts injured was observed. Approximately one-third of those
      injured required medical treatment. Predictors of injury were maximum travelling
      speed exceeding 101 km/hour (OR 4.53) and only sometimes wearing a helmet (OR
      4.10). CONCLUSIONS: Agricultural motorcycle injuries are a significant issue in
      rural areas, with potential intervention points relating to improving rider
      training and reducing specific risk-taking behaviours. IMPLICATIONS: Further work
      to investigate the efficacy of rider training interventions for agricultural
      motorcycles are warranted.

PMID- 14705290
TI  - Risky driving behaviour in young people: prevalence, personal characteristics and
      traffic accidents.
AB  - OBJECTIVES: This research aimed to examine the prevalence of risky driving
      behaviour among young people, the characteristics of those who engage in risky
      driving behaviour, and the association between risky driving behaviours and
      accident risk. METHODS: Data were gathered during the course of the Christchurch
      Health and Development Study. As part of this longitudinal study, data were
      gathered on self-reported risky driving behaviours (18-21 years), traffic
      accidents (18-21 years) and a variety of individual characteristics for 907
      participants who reported having driven a motor vehicle. RESULTS: More than 90%
      of drivers engaged in some form of risky driving behaviour. Those most likely to
      engage in frequent risky driving behaviours were: males (p < 0.0001), who
      exhibited alcohol (p < 0.0001) or cannabis abuse (p < 0.001) in adolescence, who
      were involved in violent/property crime (p < 0.01) and who affiliated with
      delinquent or substance-using peers (p < 0.05). There was a strong (p < 0.0001)
      association between the extent of risky driving behaviour and traffic accident
      risk. CONCLUSIONS: Risky driving behaviours are common among young people,
      particularly among young males prone to externalizing behaviours (substance
      abuse, crime and affiliations with deviant peers). Risky driving is strongly
      linked to traffic accident risk. IMPLICATIONS: There is a continued need to
      target risky driving behaviours among young people. Efforts to reduce risky
      driving should be targeted in particular at the high-risk group of young males
      prone to externalizing behaviours. More generally, the results suggest the need
      for a multistrategy approach to the reduction of traffic accidents that focuses
      on the full spectrum of risky driving behaviours.

PMID- 14705291
TI  - A prospective study of the costs of falls in older adults living in the
      community.
AB  - OBJECTIVE: To establish the hospital cost and three-month, post-hospital
      community and personal costs associated with older adults discharged to the
      community after a fall. The timing, incidence and the determinants of these costs
      to the various sectors were also examined. METHODS: Patients who attended the
      Emergency. Department of a teaching hospital in Perth, Western Australia, were
      asked to complete a daily diary for three months of all community and informal
      care they received due to their fall and any associated expenses. Unit costs were
      collected from various sources and used to estimate the cost of community and
      informal care. Hospital inpatient costs were estimated using a patient-based
      costing system. RESULTS: Seventy-nine patients participated with a total
      estimated falls-related cost for the three-month period of $316,155 to $333,648
      (depending on assumptions used) and a mean cost per patient of between $4,291 and
      $4,642. The hospital cost accounted for 80%, community costs 16% and personal
      costs 4% of the total. Of community and personal costs, 60% was spent in the
      first month. Type of injury was the most significant determinant of hospital and
      community costs. Extrapolating these figures to the WA population provided an
      estimate of the total hospital and three-month, post-hospital cost of falls of
      $24.12 million per year, with $12.1 million funded by the Federal Government,
      $10.1 million by State/local government and $1.7 million in out-of pocket
      expenses by patients. CONCLUSION: In the acute and immediate post-discharge
      period, hospital costs accounted for most of the cost of care for older adults
      discharged to the community after a fall. Community and personal costs, however,
      were also incurred. The cost estimates provide useful information for planners of
      hospital and community care for older people who have sustained a fall.

PMID- 14705292
TI  - Work-related injury in NSW hospitalisation and workers' compensation datasets: a
      comparative analysis.
AB  - OBJECTIVE: To undertake a comparative analysis of the New South Wales (NSW)
      Inpatient Statistics Collection (ISC) and Workers' Compensation Scheme Statistics
      (WCSS) for the 1999/2000 financial year in an attempt to evaluate their
      respective roles in the surveillance and monitoring of work-related injuries in
      NSW. METHODS: Work-related injuries in ISC were identified mainly by using the
      ICD-10 activity code and payment status and were compared with injury-related
      claims reported in WCSS. RESULTS: In 1990/2000, the majority of hospital
      separations for work-related injury involved males (86.2%) who came into contact
      with various objects, including machinery and tools, representing the most common
      mechanisms of injury, and open wounds and fractures of the upper and lower limbs
      as the most common injury nature/location. Injuries reported in the WCSS were
      also dominated by males (70%), with muscular stress while handling objects as the
      most common mechanism of injury and sprain and strain of the lower back as the
      leading nature/location of injury. The proportion of workers aged 15-19 years in
      the WCSS (1.2%) was over five times lower than the proportion of the same age
      group recorded in the ISC. CONCLUSIONS AND IMPLICATIONS: The analysis indicates
      that the ISC and WCSS complement each other in characterising the burden of work
      related injuries in NSW. Linking compensation and outcomes data, including
      hospital admissions and emergency presentations, will provide a more
      comprehensive picture of the nature and the factors contributing to work-related
      injuries. Such data will inform policy and program development aimed at reducing
      the burden of this type of injury in the community.

PMID- 14705293
TI  - Blinding of reviewers and authors.

PMID- 14705294
TI  - How many children take up smoking each year in Australia?

PMID- 14705295
TI  - What are underage smokers worth to Australian tobacco companies?

PMID- 14705296
TI  - Smoking in Queensland restaurants--will bans affect patronage?

PMID- 14705297
TI  - Public health disciplinary excellence.

PMID- 14705298
TI  - Detained asylum seekers, health care, and questions of human(e)ness.
AB  - This paper contains some personal observations of life inside Woomera Detention
      Centre and certain aspects of the detained asylum seeker experience. This is from
      my own reference point as a psychiatric nurse who in 2002 undertook a six-week
      contract at Woomera, and from my subsequent sociological reflections on this
      experience. I draw attention to the disintegrative effect of detention on the
      individual and the bleakness of everyday life symbolically expressed in forms of
      self-harm. Then, through the example of medication administration, I show the
      vulnerability of those in detention to bureaucratic procedures that become
      micropolitical sites, providing the machinery for dehumanizing acts. I conclude
      by calling for sociologists, health care workers, and the public health community
      in general to take a more active political stance against a Government and its
      policies that actively erode spirit, the body and, for some, even life.

PMID- 14705299
TI  - The year of the Salmonella seekers--1977.
AB  - In 1977 two major outbreaks of salmonella infection originated in Victoria. The
      first of these, involving Salmonella Bredeney, continued over some seven months
      and was traced to contamination of powdered milk-based infant formulae during
      manufacture. This caused cases of gastroenteritis among young children throughout
      Australia. Another incident led to the discovery that salmonella serovars were
      colonising not one, but a number of dairy factories through the State. The second
      outbreak was of typhoid, stemming from a carrier working in a sandwich bar, and
      occurred during the course of the first, almost overwhelming public health
      resources and delaying investigation of the first outbreak. The background,
      recognition, course, investigation and resolution of these, previously
      unpublished, outbreaks are described, drawing upon the experiences of authors
      involved at the clinical, public health and laboratory levels, and preserved,
      contemporary records. Taken together, these outbreaks directly stimulated radical
      improvements in the construction and management of dairy factories in the State;
      initiated the adoption of risk management concepts in food factories; caused the
      launch of regional regulations compelling notification of salmonellas found in
      food manufacture; and led to the setting-up of an enhanced national, laboratory
      based system for the collection, analysis and dissemination of information on
      enteric pathogens.

PMID- 14705300
TI  - An economic evaluation of increased uptake in Q fever vaccination among meat and
      agricultural industry workers following implementation of the National Q Fever
      Management Program.
AB  - INTRODUCTION: Q fever is a serious but vaccine-preventable infectious disease
      that predominantly affects those working in the meat and agricultural industries.
      In October 2000, the Commonwealth Government introduced the National Q Fever
      Management Program. This economic evaluation assesses the cost-effectiveness and
      cost-utility of improved vaccine uptake among meat and agricultural industry
      workers. METHODS: Separate analyses were conducted for meat and agricultural
      industry workers. Clinical and epidemiological data used to create the models
      were obtained from published sources. Markov modelling was used to estimate the
      impact of Q fever vaccination uptake on the direct costs and outcomes of Q fever
      over a 20-year period. RESULTS: Increasing vaccine uptake from 65% to 100% among
      meat industry workers results in an incremental cost per life year gained of
      $20,002, and a cost per QALY of $6,294. Increasing vaccine uptake from zero to
      20% among agricultural industry workers results in an incremental cost per life
      year gained of $24,950, and a cost per QALY of $7,984. Including some indirect
      costs in the form of Workcover payments results in cost savings for both industry
      groups. CONCLUSION: The results of this evaluation indicate that public health
      strategies to enhance the uptake of Q fever vaccine among high-risk workers
      potentially provides excellent value for the money invested.

PMID- 14705301
TI  - A community-based study of respiratory episodes in Melbourne, Australia.
AB  - OBJECTIVE: To provide recent data regarding the epidemiology of community-based
      respiratory infections in Australia. METHODS: A longitudinal study between 1997
      99 involving collection of a health diary from 600 families in Melbourne.
      RESULTS: More than 80% of study participants reported at least one respiratory
      episode over 15 months. An average of 2.2 respiratory episodes per person per
      year was reported, with a mean episode duration of 6.3 days. On average, subjects
      were symptomatic for 4.2% of the study days. Compared with other age groups,
      children aged less than two years were most likely to have at least one
      respiratory episode, a greater number of episodes per person and the longest
      episode duration (6.8 days). Approximately, one in three (28.7%) respiratory
      episodes were associated with a doctor's visit, and one in four (23%)
      necessitated time off school or work. Exposure to other people with respiratory
      symptoms was commonly reported. CONCLUSIONS: Respiratory infections are common,
      cause a significant amount of morbidity, and are major contributors to the total
      community health burden. IMPLICATIONS: The direct and indirect costs of
      respiratory infections to the community are substantial.

PMID- 14705302
TI  - The pattern of notification and testing for genital Chlamydia trachomatis
      infection in Victoria, 1998-2000: an ecological analysis.
AB  - OBJECTIVE: This ecological study analyses routinely collected chlamydia
      notification and testing data to investigate any patterns. METHODS: Age and sex
      specific chlamydia notification and testing rates for Victoria were calculated
      for the period 1998 to 2000. RESULTS: Chlamydia notification and testing rates
      rose between 1998 and 2000. Notification rates were higher among women aged 15 to
      24 years than men of the same age (p < 0.01) and higher among 25 to 44-year-olds
      living in metropolitan rather than rural/regional Victoria (p < 0.01). Testing
      rates were higher for women than men (p < 0.01) and higher in metropolitan rather
      than rural/regional areas (p < 0.01) in all groups except women aged 15-24 years.
      CONCLUSIONS: These increasing rates highlight that chlamydia infection represents
      a substantial public health problem. IMPLICATIONS: Although these data provide
      useful information showing these rates vary with age and sex, formal
      epidemiological prevalence and risk factor studies are required.

PMID- 14705303
TI  - Establishing thresholds for influenza surveillance in Victoria.
AB  - OBJECTIVE: We aimed to review the proportion of influenza-like illness (ILI) that
      could be attributed to influenza infection over five consecutive influenza
      seasons in Victoria, to compare ILI activity with hospital admissions for
      influenza, and to develop thresholds that would indicate when ILI activity may
      coincide with increases in influenza hospitalizations. METHODS: Combined
      nose/throat swabs from patients with ILI selected from sentinel general practices
      were tested for influenza and other respiratory viruses at the Victorian
      Infectious Diseases Reference Laboratory. The proportion of ILI attributed to
      laboratory-confirmed influenza was evaluated for five consecutive surveillance
      seasons, from 1998 to 2002. The seasonal patterns of ILI and laboratory-confirmed
      influenza were compared for 2000-02. ILI surveillance from sentinel general
      practices between 1997 and 2000 was compared with hospital admissions for
      influenza extracted from the Victorian Admitted Episodes Dataset between 1994 and
      2000. RESULTS: Approximately 41% of all ILI cases from sentinel general practices
      were confirmed to have an influenza infection between 1998 and 2002. The seasonal
      pattern of ILI and confirmed influenza among patients selected from sentinel
      general practices was very similar over three influenza seasons. The trends for
      ILI rates in sentinel general practices appeared to correlate remarkably well
      with those of hospital admissions for influenza. Thresholds for ILI were defined
      as: baseline < 0.25 ILI cases/100 patients/week; normal seasonal activity 0.25
      1.5; above normal seasonal activity > 1.5-3.5; and epidemic activity above 3.5.
      CONCLUSIONS: ILI rates from sentinel general practices correspond with hospital
      admissions coded as influenza and allow the use of threshold levels to describe
      seasonal influenza activity.

PMID- 14705304
TI  - Measles vaccination coverage among five-year-old children: implications for
      disease elimination in Australia.
AB  - OBJECTIVES: To (i) assess under-reporting of measles-mumps-rubella (MMR)
      vaccinations to the Australian Childhood Immunisation Register (ACIR); (ii)
      estimate MMR coverage among five-year-old children and the proportion immune to
      measles infection; (iii) identify factors related to non-uptake of MMR
      vaccination. METHODS: We analysed ACIR data for a birth cohort of approximately
      64,000 children aged five years. The parents of a sample of 506 children with no
      ACIR record for the second MMR vaccination (MMR2), due at four years of age, were
      interviewed by telephone to assess under-reporting to the ACIR and reasons for
      non-uptake of MMR vaccination. RESULTS: Parents reported that 22% (n = 111) of
      the surveyed 506 children had received MMR2 before their fifth birthday, and 42%
      (n = 214) by approximately 5.5 years of age. After correcting for this level of
      under-reporting to the ACIR, MMR2 coverage for the entire cohort at five years of
      age was 52.9% (95% CI 52.3-53.4), and increased to 84.1% (95% CI 83.4-84.8) by
      approximately 5.5 years of age. This was 4.3% and 8.2%, respectively, higher than
      ACIR coverage estimates at the two ages. Based on the corrected MMR coverage
      estimates, 93% of the cohort was immune to measles due to vaccination. The most
      common parent-reported reason for incomplete vaccination was lack of knowledge
      about the MMR vaccination schedule. CONCLUSIONS: Measles elimination in Australia
      will require continued effort in vaccination coverage and timeliness among pre
      school children. School-entry requirements are important for MMR2 uptake.
      Strategies are needed to improve reporting to the ACIR for more accurate
      measurement of coverage.

PMID- 14705305
TI  - Cause of death in patients with end-stage renal disease: assessing concordance of
      death certificates with registry reports.
AB  - OBJECTIVES: To assess concordance in reporting, in two Australian national
      datasets, of cause of death of patients with end-stage renal disease (ESRD).
      METHODS: For deaths in 1997-99, we compared 'cause of death' and 'primary renal
      disease', as coded in the Australian and New Zealand Dialysis and Transplant
      Registry (ANZDATA), with 'underlying' and 'associated' causes of death (based on
      death certificates), as coded by the Australian Bureau of Statistics (ABS). Dates
      of birth and death and sex identified the same individuals in the two datasets.
      Deaths from the three States for which date of birth was not available from death
      certificates were excluded. Cause of death was compared at the ICD-10 chapter
      level. RESULTS: Of 1,728 ANZDATA patients from NSW, SA, WA, NT and ACT who died
      during 1997-99, 1,117 (65%) could be matched to a record in the ABS dataset for
      the corresponding jurisdictions. The death certificates of 219 (20%) of these
      1,117 patients made no mention of chronic renal failure. Overall, agreement on
      cause of death was poor (kappa = 0.22). Using ANZDATA information on cause of
      death and ABS underlying cause of death, only 38% of patients had the same cause
      (at the ICD-10 chapter level) recorded in both datasets. Additional information
      on primary renal disease (ANZDATA) and up to 12 associated causes of death (ABS)
      was required to obtain substantial agreement. CONCLUSION AND IMPLICATIONS: Death
      certificates and ANZDATA records provide differing causes of death for ESRD
      patients. Information from these sources was not directly comparable. Neither
      dataset provided a complete picture of renal disease as a cause of death in
      Australia.

PMID- 14705306
TI  - Can a mortality excess in remote areas of Australia be explained by indigenous
      status? A case study using neonatal mortality in Queensland.
AB  - OBJECTIVE: To assess the extent to which indigenous status confounds the
      association between remoteness and neonatal mortality in Queensland. METHODS: We
      used routine data from the Queensland Perinatal Data Collection. Poisson
      regression modelling was used to assess confounding. RESULTS: Babies born to
      Indigenous mothers have mortality rates 2.42 times those of the rest of the
      population, regardless of whether they live in urban, rural or remote areas (95%
      CI 2.09-2.80). The babies of non-Indigenous women who live in remote areas have a
      low risk of neonatal death, similar to their rural and urban counterparts.
      CONCLUSION: In Queensland, the key demographic variable that determines neonatal
      mortality is indigenous status, not remoteness. IMPLICATIONS: Policymakers should
      not assume that an excess of a particular health problem in remote areas
      necessarily reflects equal disadvantage for all the Australians who live there.

PMID- 14705307
TI  - The test-retest reliability of habitual incidental physical activity.
AB  - OBJECTIVE: To determine the test-retest reliability of items measuring habitual
      incidental physical activity, incidental physical activity behaviour and
      sedentary behaviours. METHODS: Eighty-four subjects aged 18-65 years were
      interviewed from randomly selected households within metropolitan and rural
      Western Australia. Subjects were administered the interview on two separate
      occasions 10 days apart. Subjects were asked about habitual incidental physical
      activity (i.e. bouts performed for 10 minutes or less) performed during the week
      and on weekends. RESULTS: Intraclass correlations performed for items measuring
      incidental physical activity were generally found to be low to moderate. The
      frequency of incidental physical activity was more reliably recalled than the
      average duration spent on short trips (ICC 0.582 to 0.872 compared with 273 to
      0.551). Kappa coefficients for habitual incidental physical activity behaviour
      items were observed to have moderate-to-high (0.478 to 0.939) agreement between
      administrations. Sedentary behaviours overall showed high test-retest reliability
      (ICC 0.646 to 0.925). CONCLUSION: These findings demonstrate that adults can
      reliably recall the frequency, but not the duration, of habitual incidental
      physical activity. Thus, the frequency measured by these items could be used to
      determine the effectiveness of current Australian physical activity guidelines
      and possibly identify shifts in incidental physical activity behaviour over time.
      IMPLICATIONS: Measurement of physical activity in all domains including
      incidental physical activity is required to determine the effectiveness of
      current guidelines and implemented health promotion interventions.

PMID- 14705308
TI  - Association of obesity with anxiety, depression and emotional well-being: a
      community survey.
AB  - OBJECTIVE: To investigate the association of obesity with anxiety, depression and
      emotional well-being (positive and negative affect) in three age groups. METHODS:
      A cross-sectional survey was carried out in Canberra and the neighbouring town of
      Queanbeyan, Australia, with a random sample from the electoral roll of 2,280
      persons aged 20-24, 2,334 aged 40-44, and 2,305 aged 60-64. RESULTS: Self
      reported height and weight were used to classify participants as underweight
      (body mass index of less than 18.5), acceptable weight (18.5 to less than 25),
      overweight (25 to less than 30) or obese (30 and over). Obesity in women was
      associated with more anxiety and depression symptoms and less positive affect,
      but there were only weak and inconsistent associations in men. When factors that
      might mediate any association were controlled (physical ill health, lack of
      physical activity, poorer social support, less education and financial problems),
      a different picture emerged, with the underweight women having more depression
      and negative affect and the obese and overweight women tending to have better
      mental health than the acceptable weight group. Controlling for physical ill
      health alone accounted for the association of obesity with anxiety and depression
      in women. CONCLUSIONS: Obesity has an association with anxiety, depression and
      lower well-being in women, but not in men. The results are consistent with
      physical ill health playing a mediating role. IMPLICATION: Reducing obesity in
      the population is unlikely to have any direct effect on mental health or
      emotional well-being.

PMID- 14705309
TI  - The prevalence of mental disorders among income support recipients: an important
      issue for welfare reform.
AB  - OBJECTIVE: To estimate the prevalence of mental disorders and psychological
      distress among Australian income support recipients. METHODS: Data from the 1997
      National Survey of Mental Health and Wellbeing were used to examine measures of
      mental health, disability and use of mental health services, comparing working
      age people in receipt of government payments to those with other main sources of
      income. RESULTS: One-quarter of all income support recipients had experienced
      substantial levels of psychological distress during the previous four weeks and
      almost one in three had experienced a diagnosable mental disorder during the
      previous 12 months. Around 45% of unpartnered women with children in receipt of
      income support payments were identified with a mental disorder. In contrast,
      around 10% of people not receiving welfare reported substantial psychological
      distress and 19% had a diagnosable mental disorder. The prevalence of physical
      and mental disability was also greater among income support recipients. There was
      no difference in service use between recipients and non-recipients. CONCLUSIONS:
      Mental illness is a significant issue among income support recipients. The
      presence of a mental disorder is a substantial barrier to work and other forms of
      social participation. Mental health is an issue with relevance beyond the health
      portfolio, with implications for many domains of social policy and service
      delivery. Understanding and better assisting income support recipients with
      mental health problems will be important in welfare reform and in the
      introduction of a more active welfare system.

PMID- 14705310
TI  - Evidence-based consumer choice: a case study in colorectal cancer screening.
AB  - OBJECTIVES: To elicit community preferences for colorectal cancer (CRC) screening
      by faecal occult blood test (FOBT) using discrete choice modeling (DCM). To
      provide policymakers with information that would assist them in designing the
      future national screening program. METHODS: 301 participants in central Sydney,
      aged 50 to 70 years, at 'average' risk of CRC, participated in a face-to-face
      discrete choice study interview in which screening profiles were posed to derive
      estimates for preferences for CRC FOBT screening. RESULTS: Three characteristics
      were varied in our screening profiles, namely: benefit (CRC deaths prevented);
      potential harm (false positive induced colonoscopy); and notification policy (of
      test result). Ninety-four respondents (32%) did not trade off CRC deaths
      prevented for any reduction in harms. Twelve per cent always chose no screening.
      The remaining 56% traded benefits and harms. These latter respondents (n = 164)
      were willing to accept 853 (false positive induced) colonoscopies for one CRC
      death prevented. CONCLUSIONS: While survival was all that mattered for just over
      one-third of the sample and 12% would choose no screening, the remaining
      individuals were prepared to trade CRC deaths prevented against other
      characteristics. CRC screening will not receive unqualified community support,
      irrespective of harms. IMPLICATIONS: In any future national CRC screening
      program, consideration of these insights about community assessment of benefits,
      harms, costs and other characteristics of CRC screening is warranted.

PMID- 14705311
TI  - Social norms, social behaviours and health: an empirical examination of a model
      of social capital.
AB  - OBJECTIVE: To explore a model of social capital, specifically the association
      between socially oriented norms and behaviours and the effect that these factors
      have on the gradient between income and self-rated health across three different
      welfare states. METHOD: We used data from the 1995-97 World Values Survey, a
      cross-sectional study conducted in a variety of countries including Australia,
      United States, Sweden and Norway (n = 5,096). RESULTS: We found variation in the
      level of social capital measures across the three different welfare states.
      Socially oriented norms are not strongly correlated with each other, or with
      socially oriented behaviours. The presence of socially oriented norms or
      behaviours did not reduce the likelihood of lower income groups reporting poor
      self-rated health, relative to the highest income groups. CONCLUSIONS AND
      IMPLICATIONS: Many questions still exist regarding the relationship between
      social capital and health, including how to measure the social capital concept
      and whether and how social capital affects health, independent of material and
      economic conditions.

PMID- 14705312
TI  - Homeless young people are a vulnerable group for hepatitis C.

PMID- 14705313
TI  - Low prevalence of STIs among women in prison, but bacterial vaginosis is common.

PMID- 14705314
TI  - Sex in Australia: older Australians do it too!

PMID- 14705316
TI  - Don't push 'bans', just live smoke-free.

PMID- 14705315
TI  - Non-State terrorism: public health implications in Australia.

PMID- 14705317
TI  - Immunohistochemical proliferation markers may overestimate the growth potential
      after ionizing radiation: in vivo study in the rat anterior pituitary gland.
AB  - The effect of ionizing radiation on the expression of immunohistochemical
      proliferation markers was examined in the rat pituitary gland. Rats were
      irradiated in the pituitary region with a dose of 40 Gy, or were sham-irradiated
      as controls. Bromodeoxyuridine (BrdU) was given to the rats after one week,
      either one hour (Br-1 group) or 17 hours (Br-17 group) before perfusion fixation.
      Immunohistochemical staining for BrdU, topoisomerase II-alpha (TopoII), Ki-67
      (MIB-5), p21WAF1/Cip1 (p21), and p27Kip1 (p27) was performed. Apoptotic cells
      were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate-biotin nick end-labeling method. The mean BrdU labeling index (LI)
      and MIB-5 LI were significantly higher in the irradiated rats than in the sham
      rats in the Br-1 group. TopoII LI was higher in the irradiated rats than in the
      sham rats, although not significantly. p27-positive cells decreased in irradiated
      rats, but p21-positive cells increased more than in the sham rats. The number of
      apoptotic cells increased significantly after radiation. BrdU LIs were lower in
      the irradiated rats than in the sham rats in the Br-17 group. A few small BrdU
      positive fragments with apoptotic features were phagocytosed in the anterior lobe
      cells. These results indicate that some "immunohistochemically proliferating
      cells" subsequently undergo apoptosis in the irradiated pituitary gland. The
      values of proliferative indices should be cautiously interpreted after
      irradiation of tissue.

PMID- 14705318
TI  - Evaluation of blood flow in carotid artery stenosis using B-flow sonography.
AB  - B-flow ultrasonography can directly visualize blood streams by reflecting the
      intravascular red blood cells, and so can detect turbulent flow in vessels. B
      flow sonography was used to evaluate flow abnormalities in patients with cervical
      carotid artery stenosis, and to investigate the mechanism of large embolus
      formation that may cause distal arterial occlusion. Twenty-two patients with > or
      = 60% stenosis of the cervical carotid artery excluding cardiovascular embolism
      were examined by B-flow and color Doppler sonography. Two patients had distal
      embolism as revealed by digital subtraction angiography, 16 patients had lacunar
      infarction, and four patients had transient ischemic attacks. B-flow sonography
      demonstrated reverse flow at the poststenotic site in patients with > or = 70%
      stenosis. Increased echogenicity at the site of the stenosis was seen in patients
      with at least 80% stenosis. Prestenotic reverse flow was seen in nine patients
      with > or = 85% stenosis. The two patients with distal embolism had decreased
      echogenicity and flow velocity, and diastolic flow was absent. B-flow sonography
      could detect various turbulent flow patterns and changes in echogenicity
      associated with cervical carotid artery stenosis. Prestenotic reverse flow and
      decreased flow velocity may be potential causes of distal embolism. B-flow
      sonography is a useful method for the evaluation of flow abnormality in patients
      with carotid artery stenosis.

PMID- 14705319
TI  - Ictal onset and spreading of seizures of parietal lobe origin.
AB  - The characteristics of seizures associated with parietal lobe epilepsy were
      investigated in six consecutive patients with medically intractable epilepsy due
      to parietal lobe lesions. Intracranial electrode recordings were retrospectively
      reviewed to investigate the seizure onset symptoms and spreading patterns
      associated with the disorder. All six patients underwent implantation of subdural
      or depth electrodes and subsequent video/electroencephalography monitoring.
      Common symptoms included motionless stare, contralateral eye deviation, and head
      turn. Tonic posturing, contralateral sensory disturbance, and motor weakness were
      also seen. Asymmetrical generalized tonic and clonic seizures were seen in all
      six patients. All seizure activities began in the parietal lobe harboring the
      lesions, and then spread immediately to the adjacent lobes in most seizures,
      where the clinical symptoms were produced. The parietal lobe is a pure generator
      of seizures, whereas most clinical symptoms originate from adjacent lobes
      following seizure onset. No apparent specific symptoms other than sensory
      disturbance arising from the parietal lobe proper were recognized. Regardless of
      clinical symptoms, the seizure onset occurred in the parietal lobe harboring the
      lesion.

PMID- 14705320
TI  - Ruptured infectious aneurysm of the distal middle cerebral artery manifesting as
      intracerebral hemorrhage and acute subdural hematoma--case report.
AB  - A 21-year-old woman with severe mitral valve regurgitation due to infectious
      endocarditis was transferred to our institute in a deep coma with intracerebral
      hemorrhage and acute subdural hematoma. She had no history of head injury. Brain
      computed tomography revealed left frontoparietal intracerebral hematoma and
      adjacent acute subdural hematoma that were evacuated on the day of admission, but
      the distal middle cerebral artery (MCA) aneurysm remained undetected. Follow-up
      cerebral angiography demonstrated the distal MCA aneurysm, which had enlarged by
      25% at 2 weeks following the first operation. The aneurysm originated from a
      branch of the angular artery and was successfully resected on Day 22.
      Histological examination of the aneurysm section showed no infectious nature, but
      the final diagnosis was infectious intracranial aneurysm based on the presence of
      infectious endocarditis.

PMID- 14705321
TI  - Retrograde carotid stenting for isolated stenosis of the proximal common carotid
      artery--case report.
AB  - A 49-year-old female with a history of systemic hypertension and diabetes
      mellitus suffered transient right hemiparesis. Carotid angiography with arch
      aortography detected severe stenosis of the proximal portion of the left common
      carotid artery. The left carotid bifurcation was surgically exposed and
      retrograde catheterization was performed to approach the proximal common carotid
      artery stenosis. The lesion was dilated with a balloon catheter and successfully
      stented without complications. The left internal carotid artery was clamped
      during the procedure to avoid embolism. Retrograde carotid stenting for stenosis
      of the proximal common carotid artery is a safe and effective alternative to
      conventional surgery in selected patients.

PMID- 14705322
TI  - Venous infarction resulting from sacrifice of a bridging vein during clipping of
      a cerebral aneurysm: preoperative evaluation using three-dimensional computed
      tomography angiography--case report.
AB  - A 67-year-old woman presented with a ruptured aneurysm of the left internal
      carotid artery bifurcation. Three-dimensional computed tomography angiography (3D
      CTA) demonstrated the first segment of the basal vein of Rosenthal passing in
      front of the internal carotid artery and the anastomosis with the cavernous
      sinus, the partially hypoplastic second segment, and the superficial sylvian vein
      entering the lateral side of the sphenoparietal sinus. Dissection of the sylvian
      fissure toward the distal direction enabled transfer of the superficial sylvian
      vein to the temporal side, but the bridging vein had to be sacrificed to secure
      adequate operating space. Postoperative CT demonstrated hemorrhagic infarction at
      the left caudate head and surrounding region. Postoperative venous infarction is
      not an uncommon complication of various approaches. 3D-CTA can provide important
      information about the venous anatomy indispensable for avoiding postoperative
      venous infarction.

PMID- 14705323
TI  - Medulloblastoma of the cerebellopontine angle--case report.
AB  - A 21-year-old male patient presented with a rare cerebellopontine angle
      medulloblastoma manifesting as cerebellar and long tract involvement signs and
      symptoms. The clinical and radiological characteristics of the lesion were
      similar to extraaxial lesions of cerebellopontine angle. The histological
      diagnosis of the lesion was medulloblastoma. Surgery achieved partial removal and
      was followed by radiotherapy and chemotherapy. The patient remained well after 18
      months. Medulloblastoma of the cerebellopontine angle is a relatively rare
      clinical entity and may occur as a dural-based extraaxial mass.

PMID- 14705324
TI  - Optic nerve glioma manifesting as intratumoral hemorrhage in a pregnant woman-
      case report.
AB  - A 33-year-old pregnant woman presented with intratumoral hemorrhage in an
      astrocytoma of the left optic nerve and chiasm manifesting as poor vision in her
      left eye. Visual examination found no light perception in the left eye and
      deteriorated acuity with temporal hemianopsia in the right eye. Computed
      tomography demonstrated a round high-density mass in the suprasellar region. T2
      weighted magnetic resonance (MR) imaging showed the center of the mass as mildly
      hypointense and T2-weighted MR imaging as hypointense. Both T1- and T2-weighted
      MR imaging showed the rim of the mass as hyperintense. She delivered a healthy
      baby by cesarean section. A left frontotemporal craniotomy was then performed.
      Incision of the lateral surface of the left optic nerve revealed clotted blood
      from the left optic nerve and the left side of the chiasm. No vascular
      malformation was noted in the hematoma cavity. Histological examination revealed
      a neoplasm composed of well-differentiated astrocytic cells. No Rosenthal fibers
      were identified. The patient made an uneventful postoperative recovery. Her right
      visual acuity returned to normal, but the temporal hemianopsia in the right eye
      and the blindness in the left eye persisted. Gliomas of the anterior visual
      pathways are rare, especially in adults. The hemorrhage may have been caused by
      the hypercoagulable state associated with pregnancy. Optic nerve astrocytic
      glioma with intratumoral hemorrhage should be considered in the differential
      diagnosis of suprasellar hematoma.

PMID- 14705325
TI  - Tumefactive myelinoclastic diffuse sclerosis--case report.
AB  - A 6-year-old boy presented with mental disturbance and progressive left
      hemiparesis. Magnetic resonance imaging demonstrated large intracranial mass
      lesions with ring-like enhancement. His neurological condition deteriorated
      rapidly. Open biopsy via craniotomy was performed under the suspicion of tumor.
      Histological examination showed massive demyelination and axon preservation, but
      no tumor cells. The diagnosis was myelinoclastic diffuse sclerosis (MDS). He was
      treated with high-dose methylprednisolone and improved dramatically. MDS is a
      rare demyelinating disorder of the central nervous system that affects mainly
      children and may mimic a brain tumor. MDS must be included in the differential
      diagnosis in young patients with a brain tumor with atypical radiological
      appearance.

PMID- 14705326
TI  - Spinal intramedullary tuberculoma requiring surgical treatment--case report.
AB  - A 71-year-old male presented with multiple central nervous system tuberculomas
      including spinal intramedullary tuberculoma manifesting as occipitalgia and left
      hemiparesis. He had received medical treatment for lung and testis tuberculosis.
      Magnetic resonance imaging revealed an intramedullary lesion at the C-2 level as
      well as multiple small extramedullary and intracranial lesions. His neurological
      symptoms gradually worsened despite intensive antituberculous therapy. The C-2
      intramedullary lesion responsible for left hemiparesis was surgically extirpated.
      Postoperatively, his neurological symptoms improved gradually, and no recurrence
      was evident at the resected site. Surgical intervention is mandatory in patients
      with intramedullary tuberculoma if neurological symptoms deteriorate or lesions
      enlarge despite continuous antituberculous therapy.

PMID- 14705327
TI  - Report of Brain Tumor Registry of Japan (1969-1996).

PMID- 14705328
TI  - Revisiting the history of the dental profession in Pennsylvania: Victorian-era
      advertising trade cards.

PMID- 14705330
TI  - How to make money--even when you're out of the office!

PMID- 14705329
TI  - Journey through time. The Dr. and Mrs. Edwin F Weaver III. Historical Dental
      Museum. Temple University School of Dentistry.

PMID- 14705331
TI  - Access to front-line care: putting FMGs to the test.

PMID- 14705332
TI  - [Madeleine St-Gelais. Energy to spare. Interview by Karine Fortin].

PMID- 14705333
TI  - [Bone marrow transplantation in children. Constructive evaluation of an
      intervention for parents].
AB  - The goal of this qualitative study was to determine, through a co-construction
      process with the study participants, the needs of parents preparing for their
      child's bone marrow transplantation and to evaluate nursing interventions
      intended to facilitate their adaptation. The study was conducted with the Guba
      and Lincoln research method, in which the intervention is evaluated using a
      construction of knowledge based on different perspectives. Consequently, a
      content analysis was done to determine the aspects to be considered and establish
      specific categories. The study found that being informed rapidly, meeting other
      parents and receiving support from the extended family are all needs experienced
      by parents that help identify appropriate nursing interventions.

PMID- 14705334
TI  - [Control of vancomycin resistant enterococcus and methicillin resistant
      staphylococcus aureus bacteria gaining every day].

PMID- 14705335
TI  - [Caring as a way of life].

PMID- 14705336
TI  - [Renewing the image of the Lebanese nurse].

PMID- 14705337
TI  - [Respiratory tract infections: a critical problem in the elderly in the winter].

PMID- 14705338
TI  - Inquiry turns spotlight on elder abuse.

PMID- 14705339
TI  - Perks of the job.

PMID- 14705340
TI  - Open access transforms care.

PMID- 14705341
TI  - Nurse reporting of adverse events caused by medicines.
AB  - Even though all drugs are extensively tested before marketing, the need for
      continuous postmarketing surveillance is now greater than ever. In 2002, 16,176
      adverse drug reaction reports were received, of which 67 per cent related to
      reactions categorised as 'serious'. Nurse reporting of adverse drug reactions has
      almost doubled in the past year since nurses were officially allowed to
      participate in the yellow-card scheme for identifying adverse drug reactions (NT
      Clinical news, 2 December, p7). Nurses, through their close contact with
      patients, are ideally placed to be a key source of information on adverse drug
      reactions in the UK's yellow-card scheme.

PMID- 14705342
TI  - What you need to know about .... vitiligo.

PMID- 14705343
TI  - An assessment of the clinical effectiveness of surgical drapes.
AB  - Questioning whether a 'sterile' material is actually sterile is something that
      many clinicians may not have considered. The equipment that comprises a sterile
      field for a major surgical or invasive procedure may also be taken for granted as
      the sterile pack would normally include sterile drapes. Under discussion is
      whether using sterile drapes is more effective than not using them. In furthering
      the debate, examination of the literature is centred on the degree of
      effectiveness of sterile drapes.

PMID- 14705344
TI  - Identifying information needs of people with multiple sclerosis.
AB  - This article reports on a survey to identify the information needs of people with
      multiple sclerosis (MS), both at the time of diagnosis and throughout the course
      of the disease. The gap between information required and received was vast. The
      greatest difficulties faced by people with MS were finding information on
      research trials; drug treatments; emotional changes; new and unusual symptoms;
      and balance and walking problems. The expressed a preferred for information
      provision through face-to-face meetings and leaflets. Although provision of
      information has improved greatly, there is still a long way to go before all
      needs are satisfied.

PMID- 14705345
TI  - Hypothermia: risk factors and guidelines for nursing care.
AB  - Hypothermia occurs when heat loss from the body exceeds heat gain and the core
      temperature of the body falls below 35 degrees C. Although death from hypotheRmia
      is rare, 80 per cent of associated mortalities are in older people. There are
      many underlying conditions that increase a person's susceptibility to cold and
      this includes not having the ability to make appropriate environmental
      adjustments to maintain body temperature. The nursing management of a patient
      with hypothermia depends upon the severity of the condition. The nurse's primary
      concern is to treat the symptoms and re-warm the patient appropriately.

PMID- 14705346
TI  - The rewards of neuro-disability nursing.

PMID- 14705347
TI  - Implant exposure techniques with second-stage surgery. Interview.

PMID- 14705348
TI  - Protect and serve.

PMID- 14705349
TI  - But baby look at you now.

PMID- 14705350
TI  - Managing society's difference and diversity.
AB  - The need for nurses to be more culturally sensitive to deliver better health care
      to minority ethnic groups is the subject of this article. The author argues that
      there needs to be better understanding of equality, more value placed on
      diversity, better recognition of racism and active challenging of racism when and
      where it occurs in health care.

PMID- 14705351
TI  - Management of constipation.

PMID- 14705352
TI  - An introduction to anorexia nervosa and bulimia nervosa.
AB  - Nurses may come into contact with patients who have anorexia nervosa and bulimia
      nervosa. The authors discuss the signs and symptoms of these illnesses and
      outline treatment options for patients with eating disorders.

PMID- 14705353
TI  - Central venous access and handwashing: variability in policies and practices.
AB  - This study examined variability in handwashing policy between hospitals,
      variability in handwashing practices in nurses and how practice differed from
      policy in tertiary paediatric hospitals in Australia and New Zealand. Eight of
      the possible nine major paediatric hospitals provided a copy of their handwashing
      and/or central venous access device (CVAD) policies, and 67 nurses completed a
      survey on their handwashing practices associated with CVAD management. A high
      degree of variability was found in relation to all the questions posed in the
      study. There was little consistency between policies and little agreement between
      policies and clinical practice, with many nurses washing for longer than required
      by policy. Rigour of handwashing also varied according to the procedure
      undertaken and the type of CVAD with activities undertaken farther from the
      insertion site of the device more likely to be performed using a clean rather
      than an aseptic handwashing technique. As both patients and nursing staff move
      within and between hospitals, a uniform and evidence-based approach to
      handwashing is highly desirable.

PMID- 14705354
TI  - Why we need ethics committees.

PMID- 14705355
TI  - Skin assessment: improving communication and recording.

PMID- 14705356
TI  - Safeguarding the young.

PMID- 14705357
TI  - Community children's nursing: a student nurse's perspective.

PMID- 14705358
TI  - Screening for retinopathy of prematurity.

PMID- 14705359
TI  - Hospital lunches: giving children choice.

PMID- 14705360
TI  - Careers in child health nursing: the influence of course experiences.
AB  - Findings presented in this paper are drawn from a longitudinal study of nurses'
      careers (Robinson et al 1998, 1999). As part of this study, a large cohort of
      child branch diplomates were asked about their clinical experience while on the
      course and its effects on their initial work plans. For 12 of the 23 specialties
      listed, more than half of the 634 respondents felt that they did not have
      sufficient experience to comment. Findings indicate that there were five
      specialties which more than half of those who had experience during the course
      felt encouraged to work in: general paediatrics (73 per cent), community (63 per
      cent), oncology (60 per cent), PICU (59 per cent), and cardiac (53 per cent).
      Overall, course experiences were more likely to encourage than discourage
      diplomates from wanting to work in a particular specialty; this was the case for
      19 of the 23 specialties. Course experiences were significantly more likely to
      have discouraged than encouraged diplomates from considering working in theatres
      and psychiatry. Seventy-seven per cent of respondents (417) had obtained a first
      job in their preferred clinical specialty. Findings from this study indicate that
      course experiences influence the initial career plans of child branch diplomates.
      Data obtained from further phases of this longitudinal study will indicate to
      what extent course experiences influence later career decisions.

PMID- 14705361
TI  - Critical care education: a collaborative approach.

PMID- 14705362
TI  - The clinical applications of mineral trioxide aggregate.

PMID- 14705363
TI  - The dental health of 5-year-old children from disadvantaged schools in the
      Eastern Regional Health Authority area 2000.
AB  - BACKGROUND: An oral health promotion project targeted at 5-year-old children in
      schools designated as disadvantaged was piloted by the Dental Health Foundation.
      The dental health of some of the children in the project was assessed. RESULTS:
      It was found that in senior infant classes in schools designated as socially
      disadvantaged, fewer children were decay free and the mean dmft was higher
      compared with data from the most recent survey of children at national schools.
      Schools with an additional disadvantaged rating (part of the 'Breaking the Cycle'
      scheme) had even fewer children who were decay free, a higher mean dmft and an
      increased proportion of the dmft was made up of untreated disease. CONCLUSION:
      The Department of Education and Science's designation of a school as
      disadvantaged is a marker for poor dental health.

PMID- 14705364
TI  - The National Dental Nurse Training Programme of Ireland.
AB  - The National Dental Nurse Training Programme of Ireland will commence in January
      2004. This is the first Irish national training programme for dental nurses. It
      has been recognised by the Dental Council of Ireland as being suitable for
      purposes of registration on the Dental Nurse Register. The purpose of this
      article is to bring this training programme to the attention of Irish dental
      practitioners.

PMID- 14705365
TI  - Voluntary health care for children with unrepaired cleft lip and cleft palate in
      developing countries--a personal perspective.

PMID- 14705366
TI  - [Nutritional deficiencies should not happen].

PMID- 14705367
TI  - [Current postural systems omit spastic patients].

PMID- 14705368
TI  - [One who communicates is a nurse].

PMID- 14705369
TI  - [Those who are competent must be reinforced].

PMID- 14705370
TI  - [Nursing assessment for reducing nursing needs].

PMID- 14705371
TI  - [Pilot prospective study of prosthesis needs at the prosthesis service of the
      CCTOS of Abidjan].
AB  - Studies on the dental health in Ivory Coast showed that the specific needs in
      prosthesis are numerous. Are there covered? What are the rates of the prosthetic
      consumption? It is to this question that the authors of the present work wanted
      brought a beginning of answer through a pilot prospective survey on the
      prosthetic demand to the service of prosthesis of the CCTOS of Abidjan. This
      survey was about 150 patients of all sex and all age come specifically for
      prosthetic rehabilitation, during the active period of February to April 1994. It
      takes out again of this survey this following results: from a general
      epidemiological point of view, the women are more numerous than the men, with an
      access frequency of 56%. Most topics are young, with an age between 20 and 30
      years. The "social" rates that convenient the CCTOS attract the patients whose
      economic income is little important gladly or that are deprived of a health
      insurance. The prosthetic antecedents show that more than 65% of the topics never
      carried mainly a prosthesis for lack information or for lace money. Among the
      topics that already underwent a prosthetic treatment, prosthesis associate
      partial resin is the more frequently recovered in spite of an interesting rate of
      fixed prosthesis (37% of carriers). The clinical data reveal that aesthetic
      remains the main motive of the consultation, with 58% of demands and the
      prosthesis associate resin is in more of 70% of the cases the chosen therapeutic
      option.

PMID- 14705372
TI  - Dental radiographic features of impacted third molars and some management
      implications.
AB  - The objective of the study was to determine the principal dental radiographic
      features of impacted third molars and to highlight some management implications,
      255 periapical radiographs belonging to 197 patients with the clinical records
      were examined. The age of the subjects, sex, and degree of impaction,
      inclination, depth, mesiodistal space and associated pathology were documented as
      well as the number of roots and their relationship to the neurovascular bundle.
      The mean age was 23.4 years with more female teeth (152, 59.6%) than male (103,
      40.4%). Majority were partially erupted (223, 91.4%) with vertical impaction most
      commonly seen in 80 teeth (31.4%). Over half of the teeth (135, 52.9%) had no
      obvious relationship with the inferior alveolar neuro-vascular bundle and where
      this existed, darkening of the root was the most common radiographic indicator
      (55 teeth, 21.6%). Most of the teeth (54.9%) had no obvious pathologic changes
      associated. In those with pathologic changes, periodontal bone loss and a wide
      follicle were most commonly observed (44 teeth or 17.3% in both cases). Older
      subjects had significantly more periodontal bone loss (p = 0.001). Periapical
      radiographic examination can reveal vital information for treatment planning of
      impacted teeth and the monitoring of asymptomatic teeth.

PMID- 14705373
TI  - [Alternatives to radiography for determining root canal length].
AB  - Location of the apical foramen using an electronic apex locator to determine
      working length is more accurate than using radiographs alone. The Neosono Co
      pilote is not adversely affected by the presence of sodium hypochlorite and gives
      us acceptable results in dry canals. Hence, it is today possible to realize
      endodontic treatment without X ray determination.

PMID- 14705374
TI  - Oral hygiene, dietary pattern and smoking habits of Bedouin (nomadic Arabs)
      population in Saudi Arabia.
AB  - The estimated population of the Bedouins are up to two million in the Kingdom of
      Saudi Arabia, but relatively little information is available about them. The aim
      of the study was to assess the oral hygiene dietary pattern and smoking habits of
      Saudi Bedouins population around Medina, Qaseen and Khamis Moshayte areas. Five
      hundred and twenty five Bedouins (296 male, 229 female) with the age range 2-90
      years were interviewed and examined clinically over a period of four months (July
      to October 1998). It was found that 25% of the subjects were miswak users, 30%
      used miswak and tooth brush, while 26% never cleaned their teeth. Almost 50% of
      the subjects were regular in their oral hygiene habits. Seventy percent were rice
      eaters while meat and dates were second and third preference. Tea was the most
      common drink with 2-3 teaspoons of sugar per cup. Only ten percent were cigarette
      smokers and less than 5% used shisha (traditional smoking pipe). It is concluded
      from the study that within the surveyed Bedouin population one fourth of them
      never cleaned their teeth while almost the same number used miswak (Chewing
      stick) to clean their teeth. Rice was the most common food item, while tea with
      refined sugar was the most common drink. Only 15% were smoker. Further research
      is needed with a larger and a more representative sample of Bedouins from the
      Kingdom of Saudi Arabia.

PMID- 14705375
TI  - Oral hygiene status and occlusal characteristics of orthodontic patients at
      University College Hospital, Ibadan, Nigeria.
AB  - Patients seeking orthodontic care are expected to maintain good oral hygiene
      status and there is still a debate as to whether occlusal characteristics are
      associated with oral hygiene status and invariably periodontal health. The aims
      of this study were to assess the pattern of oral hygiene status (OHS) of
      orthodontic patients at University College Hospital (UCH), Ibadan, Nigeria and to
      ascertain possible relationship between their OHS and occlusal characteristics. A
      prospective study of 178 consecutive orthodontic patients (44.4% males and 55.6%
      females) with mean age of 16.21 +/- 7.81 years seen in the hospital between
      January 2000 and September 2002 was done. Oral hygiene status was assessed using
      Greene and Vermillion simplified oral hygiene index while occlusal
      characteristics were assessed using Angle's classification of malocclusion and
      Jackson's method for overjet and overbite relationships. In all, 59.6%, 38.2% and
      2.2% had good, fair and poor oral hygiene status respectively. Generally, no
      significant relationship was found between oral hygiene status and various
      occlusal features (P > 0.05). It was concluded that the patients had satisfactory
      oral hygiene status and the various occlusal features did not affect their oral
      hygiene status significantly.

PMID- 14705376
TI  - [Gingival risks of fixed prostheses at the Institute of Odontology and
      Stomatology of Dakar (I.O.S.)].
AB  - The realisation of a bridgework involves a direct action on the gingival marginal
      edge. It is submitted to peremptoriness of execution that one of the objectives
      is to respect the periodontium with a great rigour. In the opposite case it can
      become a greater aggression agent, source of prosthetic failures we carried out
      this report in order to evaluate in the framework of a pedagogic operational
      programme of crown and bridge prosthesis, the superficial periodontal risks
      linked to the preparation of the abutment teeth and to the prosthetic chain. We
      examined a randomised sample of 50 patients chosen from the Dakar LOS prosthetic
      consultation. On the periodontium initially sound we noted inflammatory lesions
      of the superficial periodontium from the beginning to the end of the treatment we
      used the Russel periodontal index. The whole individual scores summarised on a
      collective chart have been submitted to the statistical analysis of the
      independence by using the chi-square test. The population consulting in bridge
      work at the Dakar LOS is relatively young, 33 years in a average with a sex ratio
      of 1.17 and it shows a moderate (60% of the cases) and severe periodontal seizure
      (40% of the cases) dealing significantly with the type of prosthesis and the
      axial and occlusal morphology of the prosthesis pieces. This study shows that
      prosthesis rehabilitation in the frame work of a clinical training at the Dakar
      I.O.S. includes relatively high risks of periodontium aggression that we would
      minimise by setting more correctly the indications of the bridge work and by
      bringing more rigour to the record and the postpone of the patients occlusion in
      the laboratory conception of the prosthesis pieces.

PMID- 14705377
TI  - [Therapeutic possibilities for multiple caries in children].
AB  - The exaggerated consumption of sugars under its various associate shapes to an
      insufficiency of mouth and tooth hygiene could drag some tooth decays. These
      tooth decays, when they demonstrate, leads to a destruction of the temporary
      teeth, with for corollaries of the aesthetic and functional problems. The
      therapeutic are not always apparent especially when there is coexistence of
      coronary destruction to juxtapose to the gum without reaching pulp with some
      precocious a toothlessing. The authors, across some cases clinics treated to the
      breast of service of Paediatric Dentistry shows different types of therapeutic
      possibilities in function of the shapes clinics. He was about conservative
      treatments or of extraction, of prothesis restorations to the aide of the Crown
      order form, of infantile removable prosthesis and of composite prosthesis.

PMID- 14705378
TI  - GERD pathogenesis, pathophysiology, and clinical manifestations.
AB  - Gastroesophageal reflux disease (GERD) is a specific clinical entity defined by
      the occurrence of gastroesophageal reflux through the lower esophageal sphincter
      (LES) into the esophagus or oropharynx to cause symptoms, injury to esophageal
      tissue, or both. The pathophysiology of GERD is complex and not completely
      understood. An abnormal LES pressure and increased reflux during transient LES
      relaxations are believed to be key etiologic factors. Prolonged exposure of the
      esophagus to acid is another. Heartburn and acid regurgitation are the most
      common symptoms of GERD, although pathologic reflux can result in a wide variety
      of clinical presentations. GERD is typically chronic, and while it is generally
      nonprogressive, some cases are associated with development of complications of
      increasing severity and significance.

PMID- 14705379
TI  - Extraesophageal symptoms of GERD.
AB  - Gastroesophageal reflux disease (GERD) can be the primary cause of, or an
      aggravating contributor to, a wide variety of conditions affecting
      extraesophageal structures. As a result, GERD can lead to a number of pulmonary
      symptoms and diseases, otolaryngologic findings and symptoms, and other
      extraesophageal manifestations, including dental erosions. Clinicians must be
      aware of the possibility of these extraesophageal reflux-related conditions, even
      in the absence of classic esophageal symptoms of GERD. While antireflux therapy
      is often helpful, response to treatment is less predictable than it is for
      typical GERD.

PMID- 14705380
TI  - The continuum of GERD complications.
AB  - Complications of chronic gastroesophageal reflux disease (GERD) run the gamut
      from erosive esophagitis to esophageal cancer, but all are linked to repeated
      exposure of the esophagus to caustic gastric and duodenal acid. Progression from
      one complication to another is not clearly established across the GERD continuum,
      although there is a clear progression from the serious complication of Barrett's
      esophagus to esophageal adenocarcinoma. This review examines the range of
      complications that can arise from chronic GERD, underscoring the need to view
      heartburn as a symptom of a potentially serious condition.

PMID- 14705381
TI  - Profile and assessment of GERD pharmacotherapy.
AB  - The choice of a medical therapy to treat gastroesophageal reflux disease (GERD)
      centers around several factors, including the efficacy and safety of the agent
      and the severity of the patient's symptoms and complications. Although the
      efficacy of antacids and alginic acid has not been proven definitively in
      clinical trials, these agents are effective against mild GERD symptoms in
      clinical practice. Along with sucralfate, these agents are also useful in special
      populations, such as pregnant women, for whom acid-suppressive therapy may not be
      the best option. The withdrawal of cisapride from the US market has lessened the
      role of promotility agents for treating GERD, as their efficacy must be weighed
      against their side effects. Acid-suppressive agents have become the drugs of
      choice for GERD. Both proton pump inhibitors (PPIs) and histamine H2-receptor
      antagonists effectively and safely treat GERD. However, PPIs have been shown to
      provide the highest levels of GERD symptom relief and esophageal healing to the
      most patients, in the shortest time, and with the fewest side effects.

PMID- 14705382
TI  - Out of the mouths of babes.

PMID- 14705383
TI  - Lost and found.

PMID- 14705384
TI  - Are you in too deep? Interview by Neil Hamilton.

PMID- 14705385
TI  - In small doses.

PMID- 14705386
TI  - Pressure points.

PMID- 14705387
TI  - Sleep and rest in patients undergoing cardiac surgery.
AB  - Sleep deficit is not uncommon in cardiac surgery patients, but research in this
      area is limited. This article examines the processes involved in sleep and how
      promoting these processes can optimise recovery in cardiac surgery patients. The
      two main parts of sleep, non-rapid eye movement and rapid eye movement, are
      believed to be responsible for the physical and psychological repair of the body.
      The combination of surgical injury, underlying disease and increased stress
      levels during hospitalisation for cardiac surgery increases the need for this
      repair. Nurses with a good understanding of sleep theories and the nursing
      process can use sleep and rest as an intervention to promote healing and prevent
      further injury after surgery.

PMID- 14705388
TI  - Communication and the hearing-impaired patient.
AB  - Hearing impairment affects significant numbers of the people who are most likely
      to use healthcare services. Nursing skills in this area still fall short of
      acceptable standards. Awareness of the scale of the problem, identification of
      those affected and knowledge of how best to communicate with them are crucial to
      providing sensitive and individualized care.

PMID- 14705389
TI  - Effective stoma siting.

PMID- 14705390
TI  - Informed consent.
AB  - It is essential that nurses are familiar with the principles and requirements of
      informed consent. This article examines the rationale and principles behind it
      and encourages nurses to reflect on how it affects their everyday practice.

PMID- 14705391
TI  - A valuable resource.

PMID- 14705392
TI  - Centennial focuses on nursing shortage.

PMID- 14705393
TI  - Early ONA history reflects service, duty to others.

PMID- 14705394
TI  - Why should nurses care about tax reform?

PMID- 14705395
TI  - Addressing workplace retention in the nursing shortage.

PMID- 14705396
TI  - Sensitivity to fragrance a growing concern.

PMID- 14705397
TI  - Developing spirituality in the curriculum: worldviews, intrapersonal
      connectedness, interpersonal connectedness.
AB  - Although many nursing education programs are searching for ways to incorporate
      spirituality into the curriculum, how this should be done remains a point of
      debate. A number of models and teaching strategies have been posed in the
      literature. This article explores how definitions of spirituality can inform the
      integration of this important concept into the curriculum. Three key themes from
      definitions of spirituality in the literature are discussed: worldviews,
      intrapersonal connectedness, and interpersonal connectedness. Strategies are
      presented for facilitating discussions around worldviews and for fostering a
      climate that promotes intra- and interpersonal connectedness for students and
      faculty.

PMID- 14705398
TI  - A pilot study to measure the caring efficacy of baccalaureate nursing students.
AB  - Caring in professional nursing, often described as the essence of nursing, has
      gained increasing attention over the past several decades. Many programs claim to
      be based on a caring philosophy and practice. Despite the expectation that
      graduates of nursing programs will develop relationships with their patients and
      practice within a caring framework, evaluation of caring competencies is not well
      developed. The purpose of this pilot study was to measure the self-reported
      caring competency of baccalaureate nursing students using the Coates Caring
      Efficacy Scale (CES) (1). Students from prenursing courses to final semester
      seniors completed the CES (N = 193). Mean scores in this cross-section of
      students were higher than those reported by Coates for novice student nurses, but
      slightly lower than those Coates reported for comparable baccalaureate seniors.
      Final semester seniors identified their families as making the greatest
      contribution to their development of caring; only a few reported the influence of
      the nursing curriculum. This study, while limited to students in one program,
      provides beginning evaluative data of self-reported caring competencies of
      nursing students.

PMID- 14705399
TI  - Developing personal and community learning in graduate nursing education through
      community engagement.
AB  - Community engagement through service-learning was introduced into a graduate
      program in nursing education to develop student leadership skills, interest in
      learning, and social responsibility. With faculty expertise and guidance,
      students worked in partnership with underserved community agencies. The goal of
      sustainability was accomplished by developing faculty expertise in service
      learning as a method of instruction and integrating community engagement into
      academic assignments within existing courses. Opportunities to reflect on the
      benefits of the experiences were considered crucial to bridging service to
      learning in the community. Evaluation findings indicate that students gained
      insight into community needs and resources as they moved outside traditional
      health care settings. Graduates increased their understanding of their role as a
      resource to the community, and community agencies saw the value of a nurse
      educated at an advanced practice level.

PMID- 14705400
TI  - Organizing and presenting program outcome data.
AB  - This article focuses on the challenging process of collecting, organizing, and
      presenting outcome data for systematic program evaluation. Critical thinking is
      used as an example of outcome criteria. The article indicates how a baccalaureate
      and master's program benefited from the development of a systematic, creative
      method of data collection, analysis, and reporting.

PMID- 14705401
TI  - Instructional tools for nursing education: concept maps.
AB  - Students must deal with vast amounts of information in multiple formats, yet
      their ability to organize and link data in a logical way varies widely. Concept
      mapping offers nurse educators a useful tool to assist nursing students in wading
      through and critically analyzing this information more effectively. This article
      explains concept/cognitive mapping as a teaching strategy for several aspects of
      course work. Types and examples of maps developed by undergraduate and graduate
      students are used as illustrations and points of discussion. Illustrations are
      assessed according to type of map, information presented, aspects of the maps
      that facilitate meaningful learning, and what information is missing. Strategies
      for remediation to help learners assimilate new information are included.
      Finally, implementation of mapping in nursing education and ideas for research in
      concept/cognitive mapping are discussed.

PMID- 14705402
TI  - Annual infection control & safety check-up.

PMID- 14705403
TI  - Type I latex allergy diagnosis ends career of Florida dental assistant.

PMID- 14705404
TI  - SGM Spadaro receives first Strickland Award.

PMID- 14705405
TI  - Cold sore fact sheet--a basic review.

PMID- 14705406
TI  - First one-day, oral antiviral for cold sores is approved.

PMID- 14705407
TI  - Canker sores.

PMID- 14705408
TI  - Myth busters.

PMID- 14705409
TI  - One for the road?

PMID- 14705410
TI  - A & E nursing in Iraq.

PMID- 14705411
TI  - Demystifying the application and interview process.

PMID- 14705413
TI  - Urinary retention: issues of management and care.

PMID- 14705412
TI  - Oxpentifylline: an advance in the treatment of frostbite.

PMID- 14705414
TI  - Developing a nurse led GP referral service.

PMID- 14705415
TI  - Proprioception exercises following ankle sprain.

PMID- 14705416
TI  - The attractions of working at Christmas.

PMID- 14705417
TI  - Research that can really change nursing care.

PMID- 14705418
TI  - Nurses back NT's campaign for action.

PMID- 14705419
TI  - Hepatitis C virus: its prevalence, implications and management.
AB  - The estimated prevalence of hepatitis C in the UK is alarming. Many people are
      unaware of their condition and the associated implications of the disease. The
      aims of this article are to provide an evidence-based update on the implications
      of being HCV positive and the role of the hepatitis nurse specialist in the
      management of patients with this virus. This article also reviews the service
      offered to patients with hepatitis by the Chelsea and Westminster Healthcare NHS
      Trust.

PMID- 14705420
TI  - What are the benefits and the pitfalls of preoperative fasting?
AB  - Preoperative fasting has been a traditional practice for many years to reduce the
      risk of aspiration while the patient is under general anaesthetic and to
      eliminate the risk of postoperative nausea and vomiting. Although it is generally
      accepted that fasting is beneficial, the fasting regimens that patients undergo
      are not dependent on the individual patient or the timing of their operation.

PMID- 14705422
TI  - What you need to know about ... scarlet fever.

PMID- 14705421
TI  - Cognitive behavioural therapy and client-centred counselling.
AB  - This article reviews the potential for combining cognitive behavioural therapy
      (CBT) and client-centred counselling (CCC) in nurse education and practice.
      Currently, CBT and CCC are practiced independently of one another within mental
      health care. This project attempted to bring together the unique qualities of
      each intervention while encouraging a synergistic approach. This was undertaken
      by developing and delivering a three-day pilot study workshop. The experiential
      workshops were evaluated using two sets of structured questionnaires and six semi
      structured interviews with randomly selected participants. A follow-up
      questionnaire was used to review the combined approach in practice.

PMID- 14705424
TI  - Typhoon-resistant dental care.

PMID- 14705423
TI  - The management of patients with spinal cord injury.
AB  - Few diseases or injuries have greater potential for causing death or having a
      devastating impact on a person's quality of life than cervical spine trauma. All
      patients admitted to hospital after significant trauma must therefore be assumed
      to have a potentially unstable spinal fracture until it is proven otherwise, to
      prevent their sustaining further injury owing to inappropriate management. It is
      vital that nurses are familiar with the signs and symptoms of such injuries and
      aware of the appropriate management techniques.

PMID- 14705425
TI  - Enhancing the dental experience. Dental Day Spa: the future is now.

PMID- 14705426
TI  - Common causes of endodontic failure.

PMID- 14705427
TI  - Effect of a dental chew on dental substrates and gingivitis in cats.

PMID- 14705428
TI  - Pulp canal obliteration in a dog.

PMID- 14705429
TI  - Surgical extraction of the maxillary canine.

PMID- 14705430
TI  - Prevalence of dental resorptive lesions in Swedish cats.
AB  - Ninety-six, randomly selected Swedish cats were evaluated for the presence of
      dental resorptive lesions. All cats were examined while receiving general
      anesthesia. Diagnosis was based on oral examination and full-mouth, intraoral
      dental radiographs. Information concerning age, sex, vaccination status, eating
      habits, food type, environment (indoor or outdoor housing), oral, discomfort,
      dental care, and medical treatment was recorded. Hematologic samples included
      analysis for FeLV, FIV, and calcivirus. Of the cats examined in this study, 32%
      had gross or radiographic signs of dental resorptive lesions. There was a
      positive relationship between the occurrence of dental resorptive lesions and
      increasing age.

PMID- 14705431
TI  - Displacement of maxillary premolar teeth in a filly.
AB  - Abnormalities of dental development such as hypoplasia of cementum, oligodontia,
      polydontia, enamel hypoplasia, brachygnathia, and prognathia are quite common in
      the horse. Abnormalities of eruption are less common and often associated with
      trauma. This case report describes the diagnosis and therapy for pre-eruption
      displacement of the maxillary left third and fourth premolar teeth resulting from
      previous facial trauma in a 1.5-year-old filly.

PMID- 14705432
TI  - Pharyngeal--laryngeal blastomycosis in a dog.

PMID- 14705433
TI  - Endodontic treatment of a tiger.

PMID- 14705434
TI  - Professional teeth cleaning.

PMID- 14705435
TI  - Regional anesthesia for dentistry and oral surgery.
AB  - Pain is a perception that results from activation of a specific set of receptors
      by noxious stimuli. Processing by the central nervous system results in the
      stimulus to be perceived as pain. Thermal receptors respond to temperature
      changes, mechanoreceptors respond to pressure, tension, stretch, and
      chemoreceptors respond to substances released during the inflammatory process
      such as prostaglandins, histamine, serotonin, and bradykinin. The current
      standard of veterinary medical practice is adequate pain management for all
      patients. Regional anesthesia is one component of overall pain management of the
      oral surgery/dental patient and is described step-by-step.

PMID- 14705436
TI  - Redefining perioperative advanced practice. Scope of practice: measuring impact
      and sustainability.
AB  - There are increasing demands placed upon the modern NHS, particularly in
      emergency care.  In combating these demands, new approaches to practice will form
      an overall  strategy for improving care delivered to patients.  This is the
      second in a series by authors from the Good Hope Hospital NHS Trust and explains
      their experience of developing an innovative approach to the management of
      surgical emergencies through the specialist nurse role in anaesthesia and
      emergency surgery.  It examines the scope of practice, clinical and operational
      impact of the role, and future developments.

PMID- 14705437
TI  - Theatre staff's knowledge of surgical face masks.
AB  - Surgical face masks have been worn for over a century. Their initial
      implementation was to reduce wound infection by reducing droplet spread from the
      surgical team's mouth and nose. More recently face masks have been worn to
      protect the surgical team from contamination from patients and hazards within the
      operating theatre. To facilitate this, a range of face masks is available. The
      commonest are the standard face mask with a filtration ability of approximately 5
      microns, and the LASER face mask with a filtration ability of 1.1 microns. The
      purpose of this study was to determine staff's knowledge of face masks.

PMID- 14705438
TI  - Advanced practitioners within the operating theatre.
AB  - While the role of the nurse within theatre is yet to be defined (NATN has set up
      a working party to define this), some theatre practitioners are being described
      as advanced practitioners and certain types of theatre practice are being
      labelled as advanced or extended. What constitutes advanced practice has
      implications for theatre practitioners, their professional development, their
      competency-based salaries and how they are viewed by other nurses outside their
      specialism.

PMID- 14705439
TI  - Patient involvement. The Derby Theatre Project experience.
AB  - Patient involvement adds power and value to service redesign. Patient views can
      be extremely powerful when influencing clinical staff. They also provide a strong
      management case for change. Patient choice should be built into any service
      redesign. A model for improvement should form a template that can be amended to
      suit patient need and should take account of patient views. Patient views should
      be objective. Patients can give a better opinion of how services should be shaped
      when given a choice of what could be done. A model should offer different routes
      along a journey so that patients can say what they would prefer to happen.

PMID- 14705440
TI  - Prone positioning made easy.
AB  - Prone positioning of patients may optimise exposure for certain surgical
      procedures. There have been many published works that discuss the advantages of
      prone ventilation and how to nurse a patient who is lying in the prone position.
      However, there are very few empirical studies that describe how to place a
      patient in the prone position. This article outlines the problems and describes a
      safe and efficient manoeuvre that minimises the risks, following moving and
      handling principles (DoH 1992).

PMID- 14705441
TI  - Doctors and nurses working together: a new day is dawning!

PMID- 14705442
TI  - [Influenza vaccination: a winning proposition for everyone].

PMID- 14705443
TI  - [Renal disease or the silent epidemic].

PMID- 14705444
TI  - [Impact of lack of resources in dialysis practice in Quebec].
AB  - The purpose of this descriptive study was to assess the impact of limited
      resources on the practice of dialysis in Quebec and to highlight certain ethical
      issues. Twelve semi-structured interviews were done with nurses in charge of 14
      dialysis centres in Quebec. A survey using self-administered questionnaires was
      also carried out between January 2000 and July 2001, with a convenience sample of
      412 patients and 156 other persons involved, including 116 dialysis nurses. Two
      discussion groups brought together sixteen stakeholders from four dialysis
      centres. The results presented here were obtained by triangulating methods and
      data. They show that access to dialysis is not limited by Quebec nephrologists,
      that patients are increasingly old and sick, that teams are working to the utmost
      of their ability and that it is difficult for nursing staff to provide optimal
      care under these conditions.

PMID- 14705445
TI  - [Transition process in adolescents with renal insufficiency].

PMID- 14705446
TI  - [Evaluation of a renal predialysis program].

PMID- 14705447
TI  - [Caring for the hospitalized hemodialysis patient. Towards a better understanding
      of comprehensive management].

PMID- 14705448
TI  - [Surgical assistance: an enrichment of the nurse's role].

PMID- 14705449
TI  - Advances in orodental research.

PMID- 14705450
TI  - A comparison between radiography and ultrasonography in the diagnosis of
      zygomatic arch fracture.
AB  - A comparison between submentovertex view radiograph and real time ultrasonography
      in the diagnosis of zygomatic arch fractures. The materials are 6 patients with
      zygomatic arch fracture alone and 6 patients with combination of zygomatico
      maxillary complex with arch fracture. In 34% of patients with zygomatico
      maxillary complex with arch fracture. In 34% of patients with zygomatico
      maxillary complex fractures, zygomatic arch fractures were confirmed by
      radiographs, in 66% of the cases the isolated arch fractures were confirmed by
      radiographs. In 100% of the cases ultrasonography confirmed arch fractures in
      both the sets of cases.

PMID- 14705451
TI  - Complications associated with rigid internal fixation of mandibular fractures.
AB  - A clinical evaluation is made in twenty patients with twenty seven mandibular
      fractures, managed with rigid internal compression plate and screw
      osteosynthesis. An analysis regarding complications of this method is made and
      discussed.

PMID- 14705452
TI  - Cytomorphometric analysis of exfoliated normal buccal mucosa cells.
AB  - Interest in the field of oral exfoliative cytology has reemerged following
      advancements in the field of quantitative oral exfoliative cytology as a powerful
      diagnostic tool. However, even though numerous such studies have been conducted
      in malignant and precancerous conditions, there have been relatively few reports
      of similar studies on the normal mucosa, which could be used as a baseline for
      comparison of pathological smears. This study was undertaken to establish the
      average nuclear diameter (ND), cytoplasmic diameter (CD), and the nuclear
      cytoplasmic (NC) ratio in normal subject and to evaluate the differences in these
      parameters, if any, between different age groups and between males and females.
      The mean ND was found to range from 7.8 u to 8.28 mu, the mean CD was found to
      range from 46.19 mu, and the NC ratio was found to range from 0.1609 to 1822. The
      results of this study also showed significant variation in the CD with increasing
      age. All parameters showed variations with age changes in females, probably as a
      result of hormonal influences.

PMID- 14705453
TI  - Antibiotic susceptibility of bacterial isolates in gingivitis and periodontitis.
AB  - The present study was conducted to isolate aerobic as well as anaerobic microbes
      from patients of gingivitis and adult periodontitis and to study the
      susceptibility patterns of these isolates to different antibiotics. In our study
      all the samples belonging to the control as well as the study groups yielded
      microbes. Aerobes and facultative anaerobes were isolated from 100 percent and 96
      percent cases of normal gingiva and orodental infections respectively. Anaerobes
      were isolated from 80 percent of the normal gingival samples and 97 percent of
      the cases of orodental infections. Metronidazole was found to be the best for the
      anaerobes while the aerobes and facultative anaerobes showed good susceptibility
      to cefazolin and cefotaxime.

PMID- 14705454
TI  - Oral melanin pigmentation in smoked and smokeless tobacco users in India. Clinico
      pathological study.
AB  - Tobacco used as smoked and smokeless form induces oral mucosal changes in which
      intra-oral mucosal pigmentation is one of the clinical manifestations. The
      melanocyte activity responsible for pigment changes is not well documented in the
      literature. The present study is undertaken to observe clinical and histological
      changes in oral buccal and labial mucosa of 41 tobacco users and compared with 8
      controls. 95.24% of smokers showed pigmentation of both labial and buccal mucosa.
      Labial mucosa showed a high degree fo pigmentation (81%) than the buccal mucosa
      (33.3%). 93.3% of alcoholics showed a high degree of pigmentation.
      Hypermelanocytosis and melanosis were observed in smokers. Pigmentation at the
      site of quid placement was absent in smokeless tobacco users but mild
      pigmentation was observed away from the site of quid placement with the
      concurrent increase in the number of melanocytes and melanocytic activity.

PMID- 14705455
TI  - Recovery and reusability of some materials used in large amounts in dentistry and
      their significance.

PMID- 14705456
TI  - Juvenile aggressive cemento-ossifying fibroma. A case report.
AB  - Juvenile Aggressive Cemento-Ossifying Fibroma is a benign, fibro osseous neoplasm
      commonly affected 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- 14705457
TI  - Nasopalatine duct cyst--a case report.
AB  - A nasopalatine duct cyst is that which occurs in or near the incisive canal. A
      case of nasopalatine duct cyst in a 14-year-old male is reported here.

PMID- 14705458
TI  - Dens in dente (dens invaginatus). Report of two unilateral and one bilateral
      case.
AB  - Dens invaginatus is a deep surface invagination of the crown or root that is
      lined by enamel. It is one of the developmental anomalies affecting the teeth. It
      commonly affects maxillary lateral incisor, followed by central incisor,
      premolar, canine and molar tooth. Maxillary teeth are more commonly involved than
      mandibular teeth. It usually occurs unilaterally although 43% occur bilaterally.
      The invagination within the tooth can be single, double and even triple has been
      reported. The affected tooth usually is thick, barrel shaped with a small round
      palatal opening to the invagination. It usually traps plaque, food debris and is
      prone for dental caries, which may lead to pulpal and periapical pathology. So if
      detected early the dens invaginatus should be prophylatically restored. Two
      unilateral and one bilateral case of dens invaginatus are reported here.

PMID- 14705459
TI  - Intra-oral hypermelanosis in an HIV sero-positive patient--a case report.
AB  - A 32 year old HIV sero positive male patient reported to the Ragas Dental College
      Annexure at Voluntary Health Services Hospital, Chennai for evaluation of oral
      health status. He had no history of any drug or tobacco usage. Intra oral
      examination revealed pigmentation in the buccal mucosa on both sides, which was
      increasing over the past six months. Histopathologic evaluation of the hyper
      pigmented lesion was done, using routine Haematoxylin & Eosin and Masson-Fontana
      stains. The hyper pigmentation was observed to be as a result of increased
      melanin production in the epithelium. The pathogenesis of hypermelanosis intra
      orally in HIV sero-positive patients is discussed in this article.

PMID- 14705461
TI  - At risk of getting nailed.

PMID- 14705463
TI  - Continuing education for nurses. Hospice 101.

PMID- 14705464
TI  - An 'invisible' workforce.

PMID- 14705467
TI  - Sharing a vision. Building an alliance.

PMID- 14705468
TI  - Perioperative care for patients with sickle cell who are undergoing total hip
      replacement as treatment for osteonecrosis.
AB  - Sickle cell disease, which is characterized by chronic hemolytic anemia, is
      prevalent in the United States. In addition to the profound multisystem effects
      of vasoocclusion associated with sickle cell disease, osteonecrosis of the
      femoral head classically develops at an early age. Because of advanced medical
      technology and new treatment modalities, patients with sickle cell disease are
      living longer. More adults with this genetic disease are becoming candidates for
      total hip arthroplasty. This article describes the pathophysiology of sickle cell
      anemia, explains the process of osteonecrosis, and discusses total hip
      arthroplasty in this unique patient population.

PMID- 14705469
TI  - Effects of coping instruction in reducing young adolescents' pain after major
      spinal surgery.
AB  - BACKGROUND: Enduring pain following major orthopaedic surgery is a major
      challenge for adolescents. PURPOSE: To evaluate the effects of coping instruction
      and concrete-objective information on adolescents' postoperative pain and focus
      on potential applications of these interventions for orthopaedic nursing
      practice. DESIGN/METHOD: A randomized controlled trial of 66 young adolescents
      (age 11-14) undergoing major spinal surgery for idiopathic scoliosis. RESULTS:
      The intervention that focused only on coping instruction was the most effective
      intervention on postoperative Day 2. On postoperative Day 4, adolescents
      receiving coping instruction (coping alone or coping plus information) reported
      less pain than those not receiving coping instruction. DISCUSSION: Interventions
      that direct adolescent patients' attention to learning coping strategies they can
      use during recovery to lessen pain may be more efficacious than others following
      major spinal surgery.

PMID- 14705470
TI  - Strains and sprains.

PMID- 14705471
TI  - Alternative therapies for arthritis treatment. Part 2.
AB  - Although modern medicine has been successful in managing infection and saving
      victims of multiple trauma, healthcare providers have offered little relief to
      individuals with chronic diseases, such as arthritis. Many patients with
      arthritis are seeking help with disease management from alternative therapies.
      When used along with allopathic medicine, these therapies may, in fact, increase
      quality of life for patients with arthritis. This article, second in a two-part
      series on alternative therapies, returns to the seven fields of practice
      identified by the National Institutes of Health (NIH) to explore additional
      treatment options for individuals with arthritis. Part 1 in this series was
      published in the September/October 2003 issue of Orthopaedic Nursing.

PMID- 14705472
TI  - Stimulators of bone healing. Biologic and biomechanical.
AB  - Bone is a dynamic biologic tissue. Metabolically active, the stimuli for bone
      degeneration and regeneration is influenced and modulated by biomechanical and
      biologic (cellular, hormonal, and molecular) physiologic processes. This article
      discusses the biologic and biomechanical stimulators and inhibitors of bone
      healing.

PMID- 14705473
TI  - An investigation of patient satisfaction following discharge after total hip
      replacement surgery.
AB  - PURPOSE: To investigate patient expectations of and satisfaction with in-hospital
      discharge planning after total hip-joint replacement surgery in early and late
      discharge patient groups. DESIGN: A qualitative study describing patients'
      experience of discharge planning. SAMPLE: Thirty-three consecutive patients
      requiring primary total hip-joint replacement from two metropolitan hospitals.
      METHODS: Participants completed in-depth, semistructured interviews on the day of
      discharge from the hospital and again 4 to 8 weeks later. Thematic analysis of
      the transcripts was made after comparing data from early and late discharge
      groups. FINDINGS: Attendance at preassessment clinic was facilitated acceptable
      satisfaction levels for patients in both early and late discharge groups.
      Although that written information provided was timely, restricted opportunity for
      dialogue with health professionals limited patient knowledge and understanding of
      recovery. CONCLUSIONS: Multidisciplinary teams in orthopaedic practice face the
      challenge of finding better ways to coordinate care and ensure people undergoing
      total hip-joint replacement therapy surgery have individualized care. A nurse
      mentor-coach could be one way to ensure patients' education needs in this area
      are met. IMPLICATIONS FOR NURSING RESEARCH: Future studies could investigate
      nurses' work in discharge planning and identify any influence that their holistic
      approach to care could bring to a collaborative discharge process.

PMID- 14705474
TI  - How to start a nurse-managed foot care clinic.
AB  - The goals of a nurse-managed clinic are to prevent illness and encourage an
      active participation in health maintenance by increasing patient knowledge. A
      nurse-managed clinic that focuses on foot care presents an excellent opportunity
      to provide quality care to patients who are at risk by monitoring for
      debilitating foot conditions while teaching proper foot care techniques. It is
      well documented that foot care can prevent serious complications, such as
      amputation, making it essential for patients to be educated and receive
      professional foot care. This article addresses the development of a foot care
      clinic managed and staffed by nurses.

PMID- 14705475
TI  - Caring doesn't end.
AB  - Despite the advances in healthcare technology and the new treatment regimens, all
      patients are not eligible for these treatments. Although some providers might
      indicate that there is nothing more that they can do, other healthcare providers
      do not give up on their patients and families. They continue to provide care,
      regardless of whether treatment options have been exhausted, and help these
      patients to have a "good death." The purpose of this article is to use two case
      examples to show how caring does not end but is rather transformed when intensive
      treatment ends. There is a discussion of the development of the hospice movement,
      upholding dignity and respect, and continuing to care. Recommendations for action
      that inform nursing practice are identified.

PMID- 14705476
TI  - Doing the right thing.

PMID- 14705477
TI  - Advances in radiation treatment of patients with breast cancer.
AB  - Breast cancer is the most commonly diagnosed cancer among women in the United
      States. Approximately half of all patients diagnosed with early-stage breast
      cancer receive conservative breast surgery followed by consolidative radiation
      treatment. A number of technologic advances have been made in radiation therapy
      planning and treatment that minimize early and late toxicities and may improve
      treatment outcomes. Among these are (a) the treatment of patients with large or
      pendulous breasts or cardiopulmonary disease in the prone position, (b) intensity
      modulated radiation treatment, which delivers precise, highly conformal radiation
      dose distributions within the breast by using computerized inverse treatment
      planning and intensity-modulated radiation beams to produce the required dose
      distribution, and (c) brachytherapy, which is the placement of a radioactive
      source within the lumpectomy bed. These advances are gaining national recognition
      and are available at many institutions. Nurses play a vital role in educating
      patients; therefore, nurses must have the information they need to inform their
      patients about these advances. The information in this article will allow nurses
      to help patients understand the anticipated treatment and related side effects
      and make informed decisions.

PMID- 14705478
TI  - Treating hot flashes in breast cancer survivors: a review of alternative
      treatments to hormone replacement therapy.
AB  - As the number of breast cancer survivors continues to grow, factors associated
      with quality of life are receiving increased clinical and research attention.
      This attention is imperative given the aftermath of psychological and physiologic
      side effects that commonly result from a cancer diagnosis and cancer-related
      treatments, including menopausal symptoms. Hot flashes, the most prevalent of
      these symptoms, have been shown to significantly decrease quality of life in
      women. Although manageable with hormone replacement therapy (HRT), hot flashes
      often are especially problematic in breast cancer survivors, a population that
      typically is not treated with HRT because of controversial evidence of a
      relationship among estrogen and/or progesterone and breast cancer recurrence and
      mortality. Furthermore, hot flashes commonly are more severe in premenopausal
      women who experience acute menopause as a result of chemotherapy treatment. In
      recent years, several treatment alternatives to HRT have been investigated. Given
      the significant number of women affected by breast cancer and the negative impact
      that hot flashes can have on their quality of life, this article reviews
      alternatives to HRT for reducing hot flash symptoms in breast cancer survivors.

PMID- 14705479
TI  - Advances in the treatment of bone metastases.
AB  - The skeleton is the third most common site for cancer to spread to after the
      liver and lungs. Malignancies that can cause destruction of skeletal bones
      include multiple myeloma and metastatic disease of the breast, prostate, and
      lung. Bone metastases are problematic for patients with cancer because
      accelerated bone breakdown occurs with many associated complications. One or more
      of the following problems may occur: pain, hypercalcemia, pathologic fractures,
      myelosuppression, and spinal cord compression with subsequent progressive
      immobility. Quality of life is affected negatively, and associated feelings of
      fear, grief, anger, despair, anxiety, and depression can occur. Management of
      malignancies of the bone involves a multimodal approach. Therapies include
      analgesia, hormone therapy, chemotherapy, surgery, radiation therapy, and the use
      of bisphosphonates. Nurses can be instrumental in promoting positive outcomes for
      patients with bone metastases.

PMID- 14705480
TI  - What's old is new again: patients receiving hepatic arterial infusion
      chemotherapy.
AB  - Hepatocellular carcinoma (HCC) ranks as the eighth most common cancer in the
      world. Although uncommon in North America, the incidence of HCC in the United
      States has increased by 70% since the 1980s (Yu, Yuan, Govindarajan, & Ross,
      2000). The most frequent causes of malignant hepatic disease in the United States
      are metastases from melanoma and primary tumors of the gastrointestinal tract,
      breast, and lung. Surgical resection and systemic chemotherapy are the standard
      treatments for this disease. However, surgery is not an option for patients with
      advanced disease, and the response rate from systemic chemotherapy remains low.
      An alternative therapy for patients with HCC or cancers with liver metastases is
      hepatic arterial infusion of chemotherapy directly into the liver. This method
      allows a high total body clearance and hepatic extraction to generate high
      hepatic and low systemic exposures. Nursing care of patients receiving hepatic
      arterial infusion of chemotherapy includes patient education and monitoring for
      complications.

PMID- 14705481
TI  - Palliative sedation.
AB  - Concerns about suffering usually arise as patients contemplate end of life. For
      most, an array of available therapies will alleviate suffering. However, for
      others, these therapies may not be adequate, despite impeccable assessment and
      management. In these circumstances, palliative sedation may be an option for the
      relief of suffering. As patients, families, and clinicians contemplate this
      option, controversies and concerns about hastening death, euthanasia, and
      limiting life-sustaining therapies can arise. This article explores some of these
      concerns.

PMID- 14705482
TI  - Bronchiolitis obliterans organizing pneumonia: a late complication of stem cell
      transplantation.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a late complication of
      hematopoietic stem cell transplantation. Many transplant recipients have returned
      to their community oncologists before BOOP has occurred. The etiology of BOOP in
      transplant recipients is not understood fully, but it may be associated with
      chronic graft-versus-host disease. BOOP presents both vague and common symptoms
      that can progress into respiratory failure but respond to early and appropriate
      treatment. Early recognition and treatment of BOOP are essential to improving
      survival of patients who are post-transplantation. Community oncology nurses are
      in a key position to support initiation of side-effect management. This article
      presents information about the etiology, presentation, diagnostic testing, and
      treatment of BOOP. Two case studies are included that illustrate the typical
      course of BOOP and its treatment.

PMID- 14705484
TI  - Nonmyeloablative bone marrow transplants.

PMID- 14705483
TI  - Internet message board use by patients with cancer and their families.
AB  - The Life After Cancer Care (LACC) Internet Web site and message board were
      created at a comprehensive cancer center to provide up-to-date information about
      different types of cancer, treatments, late effects, and research findings. The
      message board enables patients with cancer to exchange information on a more
      personal basis. During the 16-month period since the creation of the Web site,
      972 people logged on to the message board and 284 people posted 619 messages.
      Most (64%) posted only one message. The posted messages were related most
      frequently to cancers of the breast, gastrointestinal system, lung, gynecologic
      system, head and neck, and colon. Sixty percent of the people posting messages
      were cancer survivors; the remaining 40% were family or friends of survivors. The
      most frequent query themes were concerns about treatment, support, and long-term
      side effects of treatment. Individuals with cancer were significantly more likely
      to post messages about long-term side effects of treatment than family and
      friends. Message boards are a useful tool for sharing information with others who
      have similar experiences. Message board entry data also provide valuable
      information that can be used to refine the boards. Message boards have not been
      used traditionally in healthcare research but hold considerable promise as an
      information resource for people affected by cancer.

PMID- 14705485
TI  - Comprehensive decongestive therapy for lymphedema in patients with a history of
      cerebral vascular accident.

PMID- 14705486
TI  - Immunosuppression and vaccine use.

PMID- 14705487
TI  - Integrated care. Part I: Expanded psychosocial interventions in cancer care: an
      introduction to diversional therapy.

PMID- 14705488
TI  - Integrated care. Part II: Making each moment count: building a diversional
      therapy program.

PMID- 14705489
TI  - Bortezomib.

PMID- 14705490
TI  - Genetics.

PMID- 14705491
TI  - Evidence-based practice: recommendations for the early detection of breast
      cancer.

PMID- 14705492
TI  - Multiple chest nodules on computed tomography scan.

PMID- 14705493
TI  - Lung cancer.

PMID- 14705494
TI  - A changing paradigm for cancer treatment: the advent of new oral chemotherapy
      agents.
AB  - The development of numerous oral chemotherapy agents has led to a new paradigm in
      cancer treatment. Oral chemotherapy can be self-administered conveniently, so
      patients with cancer can receive their treatments in their homes instead of in a
      supervised and controlled healthcare environment. Cancer now is recognized as a
      treatable chronic disease, and new oral chemotherapy agents have been developed
      that offer targeted cancer treatment. Although the newer oral chemotherapy agents
      offer additional treatment options, they also pose challenges for patients and
      healthcare providers. Patient adherence and monitoring can be challenging, and
      reimbursement issues abound. Oncology nurses play a key role in assessing,
      educating, and monitoring patients receiving oral chemotherapy. In addition, they
      may be involved in assisting patients with obtaining reimbursement and, in some
      cases, may be instrumental in locating patient assistance programs. This article
      discusses patient care issues related to treatment with oral chemotherapy agents
      and provides a historical overview of their development and use.

PMID- 14705496
TI  - Patient education: the cornerstone of successful oral chemotherapy treatment.
AB  - Because patients with cancer self-administer oral chemotherapy, they typically do
      not receive the same amount of teaching and monitoring as patients receiving i.v.
      chemotherapy. Patient education is vital to promote patient safety, optimal
      dosing, and adherence to the treatment plan. Oncology nurses need to tailor their
      patient education efforts to the individual needs of each patient and use
      resources such as medication information sheets to reinforce teaching. This
      article reviews the process of teaching patients about oral chemotherapy and
      discusses the unique patient education challenges associated with orally
      administered chemotherapy.

PMID- 14705495
TI  - Pharmacology of oral chemotherapy agents.
AB  - The abundance of orally formulated chemotherapy agents reflects the expanding
      role of oral chemotherapy in the care of patients with cancer. Many oral
      chemotherapy agents have been used for a number of years, and several have been
      developed recently. Newer agents include the prodrugs capecitabine and
      temozolomide, the retinoid bexarotene, the immunomodulatory agent thalidomide,
      the protein kinase inhibitor imatinib, and the epidermal growth factor receptor
      inhibitors gefitinib and erlotinib. Each agent has unique pharmacologic
      properties, dosing, and side-effect profiles. This article reviews these agents
      from a pharmacology perspective.

PMID- 14705497
TI  - Safety considerations and safe handling of oral chemotherapy agents.
AB  - As a class of drugs, chemotherapy agents have two unique features. They have low
      therapeutic indexes, which places patients at an increased risk for medication
      errors, and they are considered hazardous drugs, which places patients and nurses
      at risk for environmental exposure. Policies and procedures for handling and
      administering oral chemotherapy agents are essential to promoting patients' and
      nurses' safety. Risk-reduction measures for administering oral chemotherapy in
      nontraditional healthcare settings, such as the home, require instituting a two
      person dose-verification system, educating everyone who will administer and
      handle these agents, and developing procedures for securely and appropriately
      storing oral chemotherapy agents. Currently, no standardized guidelines exist for
      handling oral chemotherapy agents, and institutions must develop their own
      policies and procedures. This article discusses oral chemotherapy safety
      considerations, including safe handling of these agents, and offers
      recommendations for practice.

PMID- 14705498
TI  - Reimbursement and patient assistance programs for oral chemotherapy agents.
AB  - Oncology nurses increasingly are being asked about medication insurance coverage
      for oral chemotherapy agents and other medications. In small clinic and office
      settings, nurses often are key providers of this information. Nurses need to be
      informed about Medicare's medication reimbursement guidelines and able to
      identify resources for patients. Resources may include pharmaceutical
      manufacturers, patient medication assistance programs, and medication discount
      programs. This article reviews these resources and provides tips to use them
      optimally in busy oncology practices.

PMID- 14705515
TI  - Ambulatory/office setting offers nurses new rewards ... and new challenges.

PMID- 14705499
TI  - Medication sheets for patients. Oral chemotherapy.

PMID- 14705516
TI  - Ambulatory/office nurses: on the move and online.

PMID- 14705517
TI  - Legislation banning genetic discrimination advances in Congress.

PMID- 14705518
TI  - ["High-tech" and "high-touch"].

PMID- 14705519
TI  - [Artwork of patients with premature labor].

PMID- 14705520
TI  - [Infectious endocarditis].

PMID- 14705521
TI  - [Nursing standard. Patient positioning--mobilization--promoting mobility].

PMID- 14705522
TI  - [19th Progress in Allergology, Immunology and Dermatology Congress in Davos.
      Chronic urticaria treatable in a large percentage of cases].

PMID- 14705523
TI  - [Results of the COPD health care costs study. COPD in Germany--unrecognized and
      cost intensive].

PMID- 14705524
TI  - [Influenza in Germany. "Caution! Influenza--danger"].

PMID- 14705525
TI  - ["Flu flies"].

PMID- 14705526
TI  - [Risk of bacterial contamination in parenteral feeding proven. Only 2 stystems
      and free of contamination].

PMID- 14705527
TI  - [Backache--number 1 public health disease. Do not become a patient yourself!].

PMID- 14705528
TI  - [Skin protection and skin care in nursing and geriatric nursing].

PMID- 14705529
TI  - [New: gemzar plus taxan in metastatic breast carcinoma. Optimal combination].

PMID- 14705531
TI  - [Effect of collagen hydrolysate on cartilage metabolism and cartilage
      regeneration. Positive effects].

PMID- 14705530
TI  - [Decreasing the risk of developing colorectal carcinoma. Lactic acid forming
      bacteria].

PMID- 14705532
TI  - [Hamburg 76th Congress of the German Society of Neurology with Continuing
      Education. Pain becomes visible. Imaging methods visualize pain perception and
      individual differences in pain perception].

PMID- 14705533
TI  - [Bamberg Discussions 2003. Diagnosis and therapy of urinary incontinence in
      diabetic patients].

PMID- 14705534
TI  - [Bipolar disorders. Differential therapy for control of mood swings].

PMID- 14705535
TI  - [Alzheimer dementia challenge. DemNet--engagement for better care].

PMID- 14705536
TI  - [At MEDICA 2003 the time has come for an evaluation. 10 years "loop-hole"-
      surgery].

PMID- 14705537
TI  - [Current legal aspects of cost liability. Nursing beds remain the discussion
      point].

PMID- 14705538
TI  - [Washing and nursing everyone can do--but then what?].

PMID- 14705540
TI  - Rise in HIV prompts call for 'sexual MOT'.

PMID- 14705539
TI  - [Intensified living. The meaty heart].

PMID- 14705541
TI  - Nurses highlight funding crisis at care trust.

PMID- 14705542
TI  - Preserving patients' privacy and dignity.

PMID- 14705543
TI  - Changing the perceptions of palliative care.

PMID- 14705544
TI  - A minister's response to equipment shortages.

PMID- 14705545
TI  - Raising awareness of HIV for World AIDS Day.
AB  - HIV still primarily affects two groups in the UK--gay men and black African
      communities. Recent advances have revolutionised the treatment of HIV and many
      people with the virus are able to lead full and healthy lives. Nurses can help
      people with HIV to understand that good health is not just about feeling
      physically well--it is also about emotions, thoughts, relationships, environment
      and many other aspects of life. World Aids Day is the one day a year when we
      remember all those living with and affected by HIV across the world, as well as
      those who have died.

PMID- 14705546
TI  - The nurse's role in helping patients cope with sight loss.
AB  - Patients with sight loss often have additional nursing and care needs. Nursing
      staff should be familiar with the common causes of sight loss and their
      treatment. To help patients come to terms with the distress of losing their
      eyesight, nursing staff should be aware of the implications of sight loss for
      patients and, where appropriate, refer them to the relevant support worker, such
      as an eye clinic liaison officer.

PMID- 14705547
TI  - What you need to know about ... Epstein-Barr virus.

PMID- 14705548
TI  - Implementing a staff nurse development programme.
AB  - A project was undertaken to implement a staff nurse development programme that
      was transferable across the Black Country, and which would assure the development
      of a competent and confident practitioner. This consisted of a core set of
      competencies, supported by effective supervision, performance management and
      personal development planning.

PMID- 14705549
TI  - Communicating with patients who have dementia.
AB  - It was not until the 1980s that significant research was carried out on brain
      disorders. Lack of understanding of dementia has perhaps been the reason for the
      over-emphasis on physical care, and a failure to see these patients as people
      with feelings, beliefs and values. Three therapeutic techniques to help
      practitioners increase and improve communication with people who have dementia
      are described. It may be that communication is the key to understanding and
      resolving behaviour disturbances.

PMID- 14705551
TI  - Invasive fungal infection occurring in low birthweight infants.
AB  - A national surveillance study has been launched to look at the rate of invasive
      fungal infection in low birthweight infants. The survey has been prompted by the
      rise in morbidity and mortality in pre-term infants caused by candida. The rate
      of fungal infection is estimated to be about 2 in 100 babies who are born at a
      weight below 1,500 g (Saiman et al, 2000; Stoll et al, 1996). It is likely that
      the increasing incidence is due to the improved survival rates of these very
      young babies. Fifteen years ago very premature babies would have been of 29-30
      weeks' gestation--currently they are more likely to be aged 25-26 weeks. But
      their extreme prematurity means that they need more invasive and intensive care.

PMID- 14705550
TI  - Aspergillus: the invisible threat.
AB  - Although the media constantly regales the public with stories of 'killer'
      infections, few people are aware of their daily exposure to a fungus that can
      cause fatal infections in a susceptible host. It has been estimated that at least
      as many die from invasive aspergillosis each year as from meningococcal sepsis.

PMID- 14705552
TI  - Update on oral candidosis.
AB  - Oral candidosis, commonly known as oral thrush, is usually caused by the yeast
      fungus Candida albicans (Wenzel and Pfaller, 1991). It affects the mucous
      membranes of the oral cavity, mainly the surface of the tongue, palate, cheeks
      and lips, and is the same organism that causes vaginal yeast infections.

PMID- 14705553
TI  - How to ... manage change.

PMID- 14705554
TI  - Preventive and interceptive prosthodontics: bridging the gap between restorative
      and implant dentistry. Interview.

PMID- 14705555
TI  - Nurse retention: is it worth it?
AB  - Nurse turnover costs thousands of dollars and negatively affects patient
      outcomes. Study results indicate experienced nurses perceive decreased autonomy
      and task orientation, and increased work pressure in their work environments.
      Strategies are presented to help retain RNs, save money, and improve patient
      outcomes.

PMID- 14705556
TI  - Are Chinese nurses a viable source to relieve the U.S. nurse shortage?
AB  - The viability of recruiting Chinese nurses to ease the current U.S. nurse
      shortage is examined by assessing nursing's socioeconomic status and the
      educational preparation of nurses in China. Recruiting Chinese nurses is a win
      win scenario for individual Chinese nurses, the Chinese nursing profession, and
      the two countries involved.

PMID- 14705557
TI  - Nurses as implementers of organizational culture.
AB  - Drawing from both theory and case-study data, the role of nurse leaders in
      implementing constructive organizational cultures is discussed. Constructive
      cultures create high-performance work environments, increasing both employee and
      patient satisfaction, and ultimately affecting economic performance. Nursing
      administrators aspiring to implement a constructive culture should emphasize
      people-centered values through a collective mission, strategic human resource
      management practices, and a patient service-oriented philosophy. Furthermore,
      constructive organizational cultures create successful high-performance work
      environments when nurses have positive colleague interactions and approach tasks
      in a manner that helps them experience self-actualization, while at the same time
      achieving organizational goals.

PMID- 14705558
TI  - A model for economic analysis.
AB  - The production process model is proposed as a way to guide economic evaluation of
      health care projects, programs, technology, or research. The model is illustrated
      with data from the development of a home care computer intervention.

PMID- 14705559
TI  - A balancing act: managing your personal and professional life--Part I.

PMID- 14705560
TI  - Not yet compliant with HIPAA privacy rules?

PMID- 14705561
TI  - Attending to weak signals: the leader's challenge.
AB  - Halverson and Isham (2003) quote sources that report the accidental death rate of
      simply being in a hospital is "...four hundred times more likely than your risk
      of death from traveling by train, forty times higher than driving a car, and
      twenty times higher than flying in a commercial aircraft" (p. 13). High
      reliability organizations such as nuclear power plants and aircraft carriers have
      been pioneers in the business of recognizing weak signals. Weike and Sutcliffe
      (2001) note that high-reliability organizations distinguish themselves from
      others because of their mindfulness which enables them to see the significance of
      weak signals and to give strong interventions to weak signals. To act mindfully,
      these organizations have an underlying mental model of continually updating,
      anticipating, and focusing the possibility of failure using the intelligence that
      weak signals provides. Much of what happens is unexpected in health care.
      However, with a culture that is continually looking for weak signals, and
      intervenes and rescues when these signals are detected, the unexpected happens
      less often. This is the epitome of how leaders can build a culture of safety that
      focuses on recognizing the weak signals to manage the unforeseen.

PMID- 14705562
TI  - The role of nursing leadership in establishing a safety culture.

PMID- 14705563
TI  - Persuasion through the art of storytelling.

PMID- 14705564
TI  - Improving the patient experience with information technology.
AB  - It has been proven in many different studies that information technology
      solutions can improve information transfer, workflow, and communication,
      resulting in marked improvements in patient safety and overall quality of care.
      However, equally important but not often emphasized is the potential for
      information technology to improve the patient experience by making a positive
      impact on the care that matters most to patients and their families.

PMID- 14705565
TI  - Championing change: lessons learned from one unit's struggle.
AB  - In an era that is primarily focused on cost reduction and outpatient facility
      development, justification for inpatient unit expansion projects is an issue that
      plagues most nurse managers. Championing Change encourages nursing leaders to
      develop business plans that highlights their endeavors. This concept was
      developed after witnessing first-hand a futile attempt to expand intermediate
      intensive care beds and telemetry monitoring capabilities on a
      neurology/neurosurgical unit. The experience of one unsuccessful quest of an
      expansion endeavor is discussed.

PMID- 14705566
TI  - Missionary nursing. Dispelling the myths.

PMID- 14705567
TI  - Health mission today. A closer look.

PMID- 14705568
TI  - The global HIV/AIDS crisis. Does the church really care?

PMID- 14705569
TI  - Educating for change. HIV/AIDS & the Zambian church.

PMID- 14705570
TI  - What would Jesus do now? How to prepare for missionary nursing.

PMID- 14705571
TI  - Spiritual care. What's worldview got to do with it?

PMID- 14705572
TI  - Spirituality in Korea. A fog of religion & culture.

PMID- 14705573
TI  - Short-term mission. A family affair!

PMID- 14705574
TI  - Staying healthy overseas. What you need to know.

PMID- 14705575
TI  - When mission hits home.

PMID- 14705576
TI  - Dental Q&A. Good oral hygiene.

PMID- 14705577
TI  - Oral health. Massachusetts versus the United States.
AB  - Results from the National Oral Health Surveillance System (NOHSS) provide an
      overview (at the state and national levels) of the burden of oral disease and the
      use of oral health services. Compared to national averages, Massachusetts
      residents are doing very well in terms of some broad measures, but (1) only
      average in the rate of edentulism, (2) below average in the rank of states with
      regard to its population on public water supply systems with fluoridation, and
      (3) marked by wide variations between the many in-state population groups.

PMID- 14705578
TI  - A pattern of erosive carious lesions from cocaine use.

PMID- 14705579
TI  - Drug-induced gingival overgrowth.

PMID- 14705580
TI  - Dental anatomy: the quest for the perfect restoration.

PMID- 14705581
TI  - The Alliance of the Massachusetts Dental Society celebrates 40 years.

PMID- 14705582
TI  - A portrait of the past.
AB  - Portrait painting of epochal moments changed the way in which people viewed
      events. Prior to this, words gave us our images and our imagination did the rest.
      In the twentieth century, the still photograph began to replace the historical
      painting. Both techniques gave us visual time to analyze the event. As artists,
      both Robert Cutler Hinckley and Warren Prosperi vied to make us their surrogate
      at the first ether operation. By using different methods, they gave us an
      accurate view of the event so that we can reflect on it. In Prosperi's cropped
      version, the older men and their facial expressions seem to have retained their
      joy of learning as they look forward to a better future for medicine. Hinckley's
      work, although more sedate, gives us a narrative of the history. It encompasses
      the search for adequate anesthesia and the final conquering of fear and pain that
      occurs on October 16, 1846. As a portrait of the past, it serves as a complement
      to Prosperi's modern work.

PMID- 14705583
TI  - Mood disorders and dental implications.

PMID- 14705584
TI  - A clinico-pathologic correlation. Kaposi's sarcoma (KS).

PMID- 14705585
TI  - [Motivation is smart will].

PMID- 14705586
TI  - [Surgery in superficial skin lesions (III of III). Procedure: carrying out the
      technique].
AB  - This third article closes a series about surgery in superficial skin lesions. The
      authors describe how to perform the technique of suture, both continuous and
      discontinuous suture, as well as the technique of knotting. The authors also
      describe the follow up procedures for treating a lesion, how to inform a patient
      about this procedure and the removal of the suture. At the end of this article,
      the authors include a bibliography for the entire series.

PMID- 14705587
TI  - [Hand washing. A paradigm shift].
AB  - Washing one's hands is one of the principal methods to control infections. At
      present time, various studies provide evidence that decontaminating one's hands
      with an alcohol based solution is just as effective, quicker to use and easier.
      This fact is an important paradigm change in the control over the transmission of
      infections. The objective of this article is to present and discuss the most
      relevant aspects of these new recommendations.

PMID- 14705588
TI  - [Oocyte donation].
AB  - The author analyzes when conditions warrant the donation of ovules in such cases
      as when ovaries fail to produce ovules and other cases in which a woman maintains
      her ovarian functions but has problems. The author also analyzes the requirements
      for one to be a receptor and a donor of ovules, the legal aspects related to this
      topic, and the procedure to be followed for donation of ovules.

PMID- 14705589
TI  - [Informed consent].
AB  - Once the stage of health paternalism, exercised so many times under the pretext
      of the principle of benevolence, has been overcome, treatment relationships level
      off, they become symmetrical and balanced and in this climate of a "therapeutic
      alliance", both parties, the patient and the health professional, have to merge
      their capabilities and their limitations. The health professional can not impose
      general character operational methods to follow to a patient nor interventions,
      even though clinically correct, against a patient's will; but neither does a
      patient have the right to obtain treatment in accordance with his desires if
      these are found to be in disagreement with concrete clinical recommendations for
      the case dealt with according to the health professional's criteria. We can
      summarize what has just been stated in two basic principles: 1. The health
      professional is not obliged to follow the requests of a patient if he/she does
      not consider these clinically appropriate, but in order to follow a different
      treatment method, the health professional must have the consent of the patient.
      2. In any case, if a patient opposes a treatment being applied to him/her, except
      in the few legally recognized exceptions, the health professional can try to
      persuade a patient to accept recommended treatment, but never can carry out
      treatment against the patient's will.

PMID- 14705590
TI  - [Surgery in children and adolescents].
AB  - The authors explain the second phase in surgery procedure which is known as intra
      operative, developing a standardized model of nursing care for children and
      adolescents during the intra-operative phase. This phase commences in the
      operating room from the moment the child/adolescent arrives after being brought
      from a hospital ward and lasts until the child/adolescent is transferred to the
      recovery room. The authors perform a systematic and holistic evaluation, using
      the Gordon Functional Health Patterns. The authors select the Nursing Diagnoses
      of NANDA, the North American Nursing Diagnosis Association, which most frequently
      appear in this intra-operative phase: risk of lesion, risk of infection, risk of
      hypothermia, and risk of asphyxiation. The authors also mention the potential
      complications which could appear during an operation according to the age of the
      child, the type of anesthesia used, the surgical technique used, and the overall
      health of the patient prior to surgery. Finally, the authors describe the nursing
      treatments related to the potential complications and the outlined nursing
      diagnoses.

PMID- 14705591
TI  - [Air-borne disease].
AB  - Respiratory protection is a factor which worries nursing professionals who take
      care of patients susceptible of transmitting microorganisms through the air more
      as every day passes. This type of protection covers the use of surgical or
      hygienic masks against the transmission of infection by airborne drops to the use
      of highly effective masks or respirators against the transmission of airborne
      diseases such as tuberculosis or SARS, a recently discovered disease. The
      adequate choice of this protective device and its correct use are fundamental in
      order to have an effective protection for exposed personnel. The authors
      summarize the main protective respiratory devices used by health workers, their
      characteristics and degree of effectiveness, as well as the circumstances under
      which each device is indicated for use.

PMID- 14705592
TI  - [Laryngeal mask].
AB  - A laryngeal mask is a very useful instrument to use both in easy as well as
      difficult handling situations related to the air tract. This mask is placed in
      the pharynx and it permits a patient to breathe in different modes, either
      spontaneously or mechanically. Different models are available; some even
      facilitate the tracheal intubation through the mask. The authors highlight that
      this type of mask does not protect nor isolate the air tract. As advantages, the
      authors point out its easy installation; thus, it is an alternative when an air
      tract presents difficulties; therefore, it is necessary that all personnel who
      have to deal with the air tract be aware of this mask and know how to handle it.

PMID- 14705593
TI  - [Occupational disease. Burnout syndrome].
AB  - This theoretical article, which includes a bibliographical summary, analyzes the
      burnout syndrome in all its aspect. The author presents ways to diagnose and
      prevent this syndrome and presents a series of extremely useful and interesting
      recommendations for professionals as well as businesses and organizations where
      these professionals work. This article is written from the viewpoint of
      preventing risks in the workplace.

PMID- 14705595
TI  - [Guide for process implantation].

PMID- 14705594
TI  - [Cocaine].

PMID- 14705596
TI  - [False public-private dilemma in health].

PMID- 14705597
TI  - Petri nets and the simulation of metabolic networks.

PMID- 14705598
TI  - Chemotherapy-induced cognitive dysfunction: a clearer picture.
AB  - Chemotherapy-associated cognitive dysfunction occurs in a subset of patients
      treated with adjuvant chemotherapy. Recent data suggest that development of
      chemotherapy-related anemia predisposes patients to cognitive dysfunction.
      Endogenous erythropoietin (EPO) is well recognized for its central role in
      erythropoiesis, and recombinant human EPO (epoetin alfa) is established as a safe
      and effective treatment for chemotherapy-related anemia. Treatment with epoetin
      alfa also improved health-related quality of life in anemic cancer patients
      undergoing chemotherapy, and several controlled studies have documented increases
      in quality-of-life scores correlated with increases in hemoglobin. Erythropoietin
      also plays a role in neuroprotection, presumably by activation of antiapoptotic
      genes. Erythropoietin and its receptor are expressed in neural cells of the human
      brain, and their expression is upregulated after hypoxic or ischemic injury. In
      animal models, systemic administration of epoetin alfa protects against such
      neural injury. Ongoing and future studies will determine whether epoetin alfa can
      provide neuroprotection with respect to the development of cognitive dysfunction
      in patients undergoing adjuvant chemotherapy treatment for breast cancer.

PMID- 14705599
TI  - Acute colonic diverticulitis: CT or ultrasound?

PMID- 14705600
TI  - A case of "red face": a clue to early detection of malignant melanoma?

PMID- 14705601
TI  - Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital
      cardiac arrest.

PMID- 14705602
TI  - Serum potassium level and dietary potassium intake as risk factors for stroke.

PMID- 14705603
TI  - [Beyond dialysis adequacy: objectives, modality and costs of a haemotochemistry
      tests program for chronic dialysis patients].

PMID- 14705604
TI  - Prognosis for seizure recurrence in patients with newly diagnosed
      neurocysticercosis.

PMID- 14705605
TI  - An interesting hepatic mass: splenosis mimicking a hepatocellular carcinoma
      (2003:9b).
AB  - We report a splenosis mimicking hepatocellular carcinoma in a patient with
      chronic liver disease. Knowledge of these imaging findings, including helical CT,
      angiography, CT hepatic arteriogram, CT arterioportogram, and iodized-oil CT, may
      obviate unnecessary surgery.

PMID- 14705606
TI  - [Bacteriological assessment of fresh artisan cheeses sold in Lima, Peru, and the
      presumed bactericidal action of Lactobacillus spp].

PMID- 14705607
TI  - Psychometric properties of the Impact of Event Scale - Revised.
AB  - This study investigated the psychometric properties of the Impact of Event Scale 
      - Revised (IES-R) in two samples of male Vietnam veterans: a treatment-seeking
      sample with a confirmed posttraumatic stress disorder (PTSD) diagnosis (N = 120)
      and a community sample with varying levels of traumatic stress symptomatolgy (N =
      154). The scale showed high internal consistency (alpha = 0.96). Confirmatory
      factor analysis did not provide support for a three-factor solution corresponding
      to the three subscales of intrusion, avoidance, and hyperarousal. Exploratory
      factor analysis suggested that either a single, or a two-factor solution
      (intrusion/hyperarousal and avoidance), provide the best account of date.
      However, correlations among the subscales were higher in the community sample
      than in the treatment sample, suggesting that the IES-R may be sensitive to a
      more general construct of traumatic stress in those with lower symptom levels.
      The correlation between the IES-R and the PTSD Checklist was high (0.84) and a
      cutoff of 1.5 (equivalent to a total score of 33) was found to provide the best
      diagnostic accuracy.

PMID- 14705608
TI  - 2003: A remarkable year.

PMID- 14705609
TI  - [Cards of information and informed consent. Proposal of 14 information cards for
      plastic and aesthetic surgery].
AB  - Obligation to deliver full information and obtaining enlightened assent are now,
      for the whole French practitioner, a necessary preliminary to each operation.
      Henceforth, in case of suit, the practitioner must prove the reality and the
      quality of preoperatoire information. The National Medical French Council (CNOM)
      called scientific societies attention to propose to their members some index
      standard cards, corresponding to mail medical and surgical records. The National
      Agency for Accreditation and Evaluation in Health (Anaes) defined the main
      characteristics of these documents. The authors propose fourteen information
      cards corresponding to the most currently operations of plastic and aesthetic
      surgery. They will being clear and simple, wtih a large agreement, strictly
      informative and yearly up to date. They have the label and therefore the
      scientific guarantee of French Society of Plastic Reconstructive and Aesthetic
      Surgery.

PMID- 14705610
TI  - [Increasing the dose of inhaled corticoids].

PMID- 14705611
TI  - [An anti-leukotriene combined with inhaled corticosteroids: results of the
      COMPACT study].

PMID- 14705612
TI  - [Adding a prolonged action beta-2-agonist].

PMID- 14705614
TI  - [Anti-leucotriens: for or against? Conclusion].

PMID- 14705613
TI  - [Adding an anti-leukotriene: results of the IMPACT study].

PMID- 14705615
TI  - Cardiothoracic training in the United Kingdom.

PMID- 14705616
TI  - Everything you always wanted to know about whistleblowing but were afraid to ask.

PMID- 14705617
TI  - Blowing the whistle--safely.

PMID- 14705618
TI  - The way forward for non-standard grade (trust) doctors.

PMID- 14705619
TI  - Enemy at the gates!--Tracing the path and tactics of host leukocytes in
      transplant arteriopathy.

PMID- 14705620
TI  - Primum nil nocere.

PMID- 14705621
TI  - Tacrolimus pharmacogenetics: bringing the laboratory into the clinic.

PMID- 14705622
TI  - A commitment to mental health.

PMID- 14705623
TI  - A potentially fatal mistake.

PMID- 14705624
TI  - Combating negativity.

PMID- 14705625
TI  - Chronic kidney disease: the emerging epidemic.

PMID- 14705626
TI  - Proposed PHS changes controversial.

PMID- 14705627
TI  - A nurse onstage and off.

PMID- 14705629
TI  - Current readings in nuclear medicine.

PMID- 14705628
TI  - Bubonic plague and HIV. The delta 32 connection.

PMID- 14705630
TI  - Comparison of allogeneic and xenogeneic in vitro T-cell proliferative responses
      in sensitized patients awaiting kidney transplantation.
AB  - Highly sensitized patients awaiting kidney transplantation may be potential
      candidates for future clinical trials using pig organ donors. Because of
      crossreactivity between human leucocyte antigens (HLA) and swine leucocyte
      antigens (SLA), such patients might have heightened T-cell responses to porcine
      xenoantigens. We determined whether lymphocytes from allo-sensitized patients
      displayed secondary (cyclosporine resistant) T-cell proliferative responses
      against porcine xenoantigens. Lymphocytes from six non-sensitized, seven
      sensitized [immunoglobulin G (IgG) panel reactive antibodies (PRA) 11 to 84%], 14
      highly sensitized patients (IgG PRA > 84%) and 12 healthy individuals were tested
      [in the presence and absence of Cyclosporin A (CsA)] to determine their
      proliferative response to human (allogeneic) and to porcine (xenogeneic)
      stimulator cells. Lymphocytes from all study groups showed a strong proliferative
      response to allogeneic and xenogeneic stimulator cells with no significant
      difference between non-sensitized and sensitized individuals. Addition of CsA
      (100 and 500 ng/ml) inhibited (>90%) proliferation of lymphocytes from all non
      sensitized patients to both allogeneic and xenogeneic stimulators. CsA was less
      effective at inhibiting proliferation of lymphocytes from sensitized patients and
      highly sensitized patients to allogeneic stimulators [29% (n=21) and 50% (n=42)
      respectively were resistant to CsA inhibition (100 ng/ml)]. In contrast,
      cyclosporine inhibited proliferation of lymphocytes from the majority of
      sensitized and highly sensitized patients to xenogeneic stimulator cells [14%
      (n=21) and 14% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)].
      HLA sensitized patients awaiting renal transplantation display cyclosporine
      resistant proliferative T-cell responses to allogeneic stimulators but
      proliferative responses to xenogeneic stimulators are more amenable to
      suppression by CsA. This finding suggests that humoral sensitisation to HLA
      antigens is not necessarily indicative of a heightened in vitro T-cell response
      to SLA antigens.

PMID- 14705631
TI  - "Glimpses into the world of a sick teenager", a series of drawings.

PMID- 14705632
TI  - The effect of immunoglobulin immunadsorptions on delayed xenograft rejection of
      human CD55 transgenic pig kidneys in baboons.
AB  - Delayed xenograft rejection (DXR) remains a major obstacle in discordant
      xenotransplantation. As strategies of complement inhibition and xenogeneic
      natural antibody (Ab) removal have been shown to give prolonged xenograft
      survival, we endeavored to determine whether combining these two strategies would
      lead to an additive effect in terms of graft survival. The study was initiated
      with two groups, A and B, where group A received normal kidneys and group B
      received hCD55 transgenic kidneys. Both groups underwent pre-transplant (day-1)
      total immunoglobulin (Ig) immunoadsorption (IA) and received an immunosuppression
      of cyclophosphamide, cyclosporine A, mycophenolate mofetil and corticosteroids.
      Two subsequent groups (C and D) receiving hCD55 transgenic pig kidneys were then
      performed with an 'optimized' immunosuppression (Cyclophosphamide starting 1 day
      earlier) but only group D recipients were immunoadsorbed. Biopsies taken during
      the post-transplantation period were analyzed for Ab deposition, compliment
      activation and cellular infiltration. No hyperacute rejection was observed. In
      the initial immunoadsorbed groups A and B, all baboons underwent DXR, which
      started surprisingly early (day 5 in most cases. In the subsequent two groups,
      the immunoadsorbed group D baboons also underwent DXR, again as early as day 5.
      In contrast, group C baboons did not show any signs of DXR on their day 6 biopsy
      or at their time of death. Analysis of graft biopsies from the kidneys undergoing
      rejection or with stable function showed strong deposition of anti-Gal IgM in all
      cases whereas strong complement C5b-9 deposits were only observed in biopsies at
      rejection. Cellular infiltration consisted mostly of monocytes/macrophages, was
      more pronounced in biopsies taken at rejection and was associated with a pro
      inflammatory environment involving interleukins 1alpha, 6 and 8. Our findings
      suggest non-specific Ig (anti-Gal and non-Gal Ig of all isotypes) IA or even
      incomplete IA in immunosuppressed baboon recipients of transgenic pig kidneys is
      detrimental to graft survival by being associated with an Ab and compliment
      driven rejection. We speculate that the IA were insufficient in terms of Ig
      depletion or frequency inducing an Ab rebound or that this total Ig depletion
      also removed components facilitating graft survival.

PMID- 14705633
TI  - Novel bacteriochlorine for high tissue-penetration: photodynamic properties in
      human biliary tract cancer cells in vitro and in a mouse tumour model.
AB  - Photodynamic therapy of bile duct cancer using hematoporphyrin derivative (HPD)
      and laser light of 630 nm wavelength is confined to a tumouricidal tissue
      penetration of 4 mm, which might be doubled with laser light between 700 and 800
      nm. Therefore, we investigated the photosensitising properties of a novel
      bacteriochlorine, tetrakis-pyridyl-tetrahydroporphyrin tosylat (THP) with high
      absorption at 763 nm. Two biliary cancer cell lines (BDC, GBC) were incubated
      with HPD or THP to assess cellular uptake kinetics, dark cytotoxicity, and
      photodynamic cytotoxicity (laser light exposure 1-20 J/cm2). Tumours grown from
      BDC cells in subcutaneous tissue of severe combined immunodeficient mice were
      treated with laser light of 30 J/cm2 after injection of THP. The concentrations
      that killed 50% of cells in the dark were 680 microg/ml of HPD, but > 6400
      microg/ml of THP in BDC cells, and 220 microg/ml of HPD, but 6400 microg/ml of
      THP in GBC cells. Both cell lines exhibited uptake and retention of THP and
      photodynamic cytotoxicity (up to 86% cells killed). THP induced tumour-selective
      phototoxicity in the cholangiocarcinoma model. The novel bacteriochlorine THP
      exhibits photosensitiser properties in biliary tract cancer cells in vitro and in
      vivo and could achieve deep tumouricidal tissue penetration due to
      photoactivation at 763 nm.

PMID- 14705634
TI  - Inhibitory effects of silk protein, sericin on UVB-induced acute damage and tumor
      promotion by reducing oxidative stress in the skin of hairless mouse.
AB  - This study was conducted to assess protective effect of an antioxidant protein,
      sericin, on UVB-induced acute damage and tumor promotion in mouse skin. In
      experiment 1, HR-1 hairless mice were treated with 180 mJ/cm2 of ultraviolet B
      light (UVB) once daily for 1 and 7 days. The treatment for 7 days caused red
      sunburn lesions of the skin. The intensity of red color and area of these lesions
      were inhibited by the topical application of sericin at the dose of 5 mg after
      UVB treatment. Immunohistochemical analyses showed that the application of
      sericin significantly suppressed UVB-induced elevations in 4-hydroxynonenal (4
      HNE), expression of cyclooxygenase-2 (COX-2) protein, and proliferating cell
      nuclear antigen (PCNA)-labeling index in the UVB-exposed epidermis. In experiment
      2, HR-1 hairless mice were treated with 200 nmol of 7,12-dimethylbenz [alpha]
      anthracene (DMBA) followed 1 week later by irradiation with 180 mJ/ cm2 of UVB
      twice weekly for 22 weeks. The protective effect of sericin was evident in terms
      of significant reduction in tumor incidence and tumor multiplicity at the dose of
      5 mg. The results suggest that sericin possesses photoprotective effect against
      UVB-induced acute damage and tumor promotion by reducing oxidative stress, COX-2
      and cell proliferation in mouse skin.

PMID- 14705635
TI  - Kinetic study of the riboflavin-sensitised photooxygenation of two
      hydroxyquinolines of biological interest.
AB  - 4-Hydroxyquinoline (4-OHQ) and 8-hydroxyquinoline (8-OHQ), two compounds of
      interest because of their bioactivity and their structural relation with
      bioactive products, are effectively photooxygenated when irradiated with visible
      light in the presence of riboflavin (Rf) (vitamin B2) in solution in air
      saturated water-methanol (9:1). Rf behaves as a dye-sensitiser, since both
      quinolines are transparent to visible light. 8-OHQ degrades about five times
      faster than 4-OHQ. Kinetic data obtained through time-resolved and stationary
      detection of Rf-electronically excited states indicate that a superoxide radical
      anion-mediated mechanism exclusively operates for 4-OHQ, whereas singlet
      molecular oxygen--mainly--plus superoxide radical anion is the species that
      reacts with 8-OHQ. The sensitiser Rf, which is known to photodegrade under
      visible-light aerobic irradiation, is regenerated in the presence of any of the
      quinolines through an electron transfer process that produces superoxide radical
      anion. The overall picture indicates that both quinolines act as sacrificial
      scavengers of the photogenerated oxygen species, thus preventing the
      photodegradation of Rf.

PMID- 14705636
TI  - Changes in plasma membrane protein structure after photodynamic action in freshly
      isolated rat pancreatic acini. An FTIR study.
AB  - Photodynamic action of a plasma membrane-specific photosensitizer sulphonated
      aluminium phthalocyanine (SALPC) has been found to regulate cellular signalling
      pathways. The present study aimed to investigate whether SALPC photodynamic
      action modulates the structure of plasma membrane proteins, and as control, of
      model proteins. To check the photodynamic effect, intrinsic fluorescence of model
      proteins bovine serum albumin (BSA), phospholipase A2 (PLA2), and calmodulin were
      monitored continuously during photodynamic action (SALPC 1 microM, light 14,000
      1x at > 580 nm). Significant decrease in fluorescence intensity was observed in
      BSA and PLA2, whereas the fluorescence of calmodulin was not affected. Confirming
      a major change in protein structure, difference IR spectrum revealed a
      significant downward deflection after photodynamic action in both BSA and in
      pancreatic acinar cells, whereas SALPC alone or light illumination alone resulted
      in no major deflection. Quantitative FTIR analysis indicated that in BSA,
      photodynamic action decreased the content of alpha-helix, increased the content
      of beta-turn and random structures, whereas beta-sheet remained the same; in
      freshly isolated rat pancreatic acini, photodynamic action decreased the content
      of alpha-helix and beta-sheet, increased the content of 1-turn and random
      structures. Taken together the fact that under the present experimental
      conditions SALPC mainly localized at the plasma membrane, it is concluded that
      SALPC photodynamic action directly modulates plasma membrane protein structure.

PMID- 14705637
TI  - Role of white light in reversing UV-B-mediated effects in the N2-fixing
      cyanobacterium Anabaena BT2.
AB  - The effects of various irradiances of artificial UV-B (280-315 nm) in the
      presence or absence of visible light (photosynthetically active radiation) on
      growth, survival, 14CO2 uptake and ribulose 1,5-bisphosphate carboxylase
      (RuBISCO) activity were studied in the N2-fixing cyanobacterium Anabaena BT2. We
      tested the hypothesis whether or not visible radiation offers any protection
      against UV-B-induced deleterious effects on growth and photosynthesis in Anabaena
      BT2. Attempts were also made to determine the irradiances of UV-B where
      inhibitory effects could be mitigated by simultaneous irradiation with visible
      light. Exposure of cultures to 0.2 W m(-2) or higher irradiance of UV-B caused
      inhibition of growth and survival and growth ceased above 1.0 W m(-2). 14CO
      uptake and RuBISCO activity were found to be more sensitive to UV-B and around
      60% reduction in 14CO2 uptake and RuBISCO activity occurred after exposure of
      cultures to 0.4 W m(-2) for 1 h. However, growth, 14CO2 uptake and RuBISCO
      activity were nearly normal when UV-B (0.4 W m(-2)) and visible light (14.4 W m(
      2)) were given simultaneously. Blue radiation (450 nm) was found to be the most
      effective in photoreactivation against UV-B, better than UV-A or any other light
      wavelength band. Our results demonstrate that the studied cyanobacterium
      possesses active photoreactivation mechanism(s) against UV-B-mediated damage
      which in turn probably allow survival under natural conditions in spite of being
      continuously exposed to the UV-B component present in the solar radiation.
      Continued growth of many algae and cyanobacteria in the presence of intense solar
      UV-B radiation under natural conditions seems to be due to the active role of
      photoreactivation.

PMID- 14705638
TI  - Studies on the synthesis of two hydrophilic hypocrellin derivatives with enhanced
      absorption in the red spectral region and on their photogeneration of O2*- and
      O2(1(delta)g).
AB  - To improve hydrophilicity and photoactivity of the new type of photosensitizer,
      hypocrellin, two new derivatives were synthesized through a mild reaction method
      between hypocrellion B (HB) and ethanolamine in tetrahydrofuran (THF) and their
      molecular structures were characterized by IR, NMR, MS and UV-Vis spectrometry.
      In the molecular structures of the two derivatives, the peri-hydroxylated
      perylenquinone structure of the parent HB is preserved and their photoresponses
      at 600-900 nm (the red spectral region) are enhanced markedly (the molar
      absorption coefficients at 650 nm for the two new derivatives are EAHB1 log
      epsilon = 3.72 and EAHB2 log epsilon = 3.91, respectively. In contrast, the
      parent compound HB exhibits little absorption at 650 nm). Electron paramagnetic
      resonance (EPR) spin trapping measurement and a 9,10-diphenylanthracene (DPA)
      bleaching method were employed to investigate the photodynamic action of two
      chemicals in the presence of oxygen. The quantum yields of O2(1(delta)g)
      generation of EAHB1 and EAHB2 are 0.08 and 0.45, respectively; the relative
      quantum yields of (O2*-) generation of EAHB1 and EAHB2 are 0.15 and 0.76,
      respectively, with the parent compound HB as the standard.

PMID- 14705639
TI  - UV-B-induced synthesis of mycosporine-like amino acids in three strains of
      Nodularia (cyanobacteria).
AB  - Three filamentous and heterocystous cyanobacterial strains of Nodularia,
      Nodularia baltica, Nodularia harveyana and Nodularia spumigena, have been tested
      for the presence and induction of ultraviolet-absorbing/screening mycosporine
      like amino acids (MAAs) by simulated solar radiation in combination with 395
      (receiving photosynthetically active radiation (PAR) only), 320 (receiving PAR +
      UV-A) and 295 (receiving PAR + UV-A + UV-B) nm cut-off filters. Absorption
      spectroscopic analyses of the methanolic extracts of samples revealed a typical
      MAA peak at 334 nm in all three cyanobacteria. Specific contents of MAAs had a
      pronounced induction in the samples covered with 295 nm cut-off filters after 72
      h of irradiation. In comparison, there was little induction of MAAs in the
      samples covered by 395 and 320 nm cut-off filters. High performance liquid
      chromatographic (HPLC) studies revealed the presence of two types of MAAs in all
      three cyanobacteria, which were identified as shinorine and porphyra-334, both
      absorbing maximally at 334 nm. The occurrence of porphyra-334 is rare in
      cyanobacteria. Specific content of both shinorine and porphyra-334 were induced
      remarkably only in the samples covered with 295 nm cut-off filters. The results
      indicate that in comparison to UV-A and PAR, UV-B is more effective in eliciting
      MAAs induction in the studied cyanobacteria.

PMID- 14705640
TI  - Antioxidant protection in cultured corneal cells and whole corneas submitted to
      UV-B exposure.
AB  - Several corneal pathologies are characterized by the presence of reactive oxygen
      species (ROS); therefore, we evaluated the protection afforded by pirenoxine and
      melatonin to corneal cell culture and whole rabbit cornea from ultraviolet
      exposure and other oxidant systems. Rabbit cornea cell (SIRC) plates and whole
      corneas were exposed to UV-B (80 or 800 mJ/cm2) or incubated with fMLP-stimulated
      autologous macrophages, in the presence or absence of pirenoxine or melatonin
      (10(-5) M). The protective activity of compounds was assessed by measuring
      superoxide anion formation, inhibition of oxidation and mitochondrial viability.
      Moreover the ex vivo protective effect of pirenoxine and melatonin was verified
      in the whole cornea submitted to UV-B exposure in vitro. Our experimental data
      demonstrate that pirenoxine and melatonin were able to inhibit the superoxide
      formation and oxidative effect in cell culture and whole rabbit corneas submitted
      to UV-B exposure or to incubation with fMLP-stimulated autologous macrophages.
      Mitochondrial viability was restored in epithelial cells of rabbit cornea but not
      in SIRCs. Moreover, both compounds are also able to increase ex vivo epithelial
      corneal cell defences against the in vitro UV-B induced lipid peroxidation.

PMID- 14705641
TI  - Inhibition of sulfur incorporation to transfer RNA by ultraviolet-A radiation in
      Escherichia coli.
AB  - tRNA sulfurtransferase activity was assayed in Escherichia coli cell extracts
      obtained from bacterial suspensions exposed to a sub-lethal dose of ultraviolet-A
      radiation (fluence 148 kJ m(-2)) imparted at a low fluence rate (41 W m(-2)). We
      found that the irradiation reduced the enzymatic activity to one fourth of the
      control value, indicating that ultraviolet-A exposure inhibits the synthesis of 4
      thiouridine, the most abundant thionucleoside in E. coli tRNA. Changes in the
      tRNA content of 4-thiouridine and its derived photoproduct 5-(4'-pyrimidin 2'
      one) cytosine were studied in bacteria growing under ultraviolet-A irradiation.
      In these conditions the accumulation of photoproduct was limited, and the
      kinetics of this process was non-coincident with disappearance of 4-thiouridine.
      The results, which are compatible with the fact that ultraviolet-A induces an
      inhibition of the 4-thiouridine synthesis, suggest that the effect of radiation
      on tRNA modification is relevant to tRNA photo-inactivation in growing bacteria.

PMID- 14705642
TI  - Activation of the stress-activated JNK and p38 MAP kinases in human cells by
      Photofrin-mediated photodynamic therapy.
AB  - We have examined the possible role of the stress-activated JNK and p38 protein
      kinases in cellular sensitivity following Photofrin-mediated photodynamic therapy
      (PDT). Previously we reported that immortalized Li-Fraumeni syndrome (LFS) cells
      are more resistant to Photofrin-mediated PDT compared to normal human fibroblasts
      (NHF) at equivalent cellular Photofrin levels. In the current work we report that
      Photofrin-mediated PDT increased the activity of JNK1 and p38 within 30 min in
      both cell types. However, the increased activity of JNK1 and p38 was transient in
      the sensitive NHF cells and returned back to near basal levels by 3 h after PDT.
      In contrast, the resistant LFS cells exhibited a more prolonged activation of JNK
      and p38, which lasted for at least 11 h and 7 h after PDT, respectively. Blocking
      of the p38 pathway in LFS cells by transient infection with a recombinant
      adenovirus expressing a dominant negative mutant of p38 or in HeLa cells by
      stable transfection with a dominant negative mutant of p38 had no effect on cell
      survival following PDT. These data suggest that although Photofrin-mediated PDT
      is able to induce JNK1 and p38 in human cells, the p38 pathway alone does not
      play a major role in the sensitivity of LFS cells to Photofrin-mediated PDT.

PMID- 14705643
TI  - The role of the methylene blue and toluidine blue monomers and dimers in the
      photoinactivation of bacteria.
AB  - The interactions between the phenothiazine dyes, methylene blue (MB) and
      toluidine blue (TB), and bacteria (Staphylococcus aureus, Streptococcus
      pneumoniae, Enterococcus faecalis, Hemophilus influenzae, Escherichia coli and
      Pseudomonas aeruginosa) were studied spectrophotometrically. This demonstrated
      that a metachromatic reaction took place between the dyes and bacteria.
      Furthermore, bacteria induced additional dimerization of MB and TB. The effective
      dimerization constants of MB and TB were evaluated in the presence of each
      bacterial strain at a concentration of 10(8) CFU/ml. The analysis of the
      effective dimerization constants for MB and TB in the presence of bacteria
      indicated that the ability to form dimers was greater for TB than for MB. Gram
      negative bacteria induced the dye dimerization more intensely than gram-positive
      bacteria. There was a correlation between the ability of each dye to form dimers
      in the presence of bacteria and the relative photobactericidal efficacy of each
      dye against these bacteria. These results provide evidence confirming the
      essential role of the dye dimers in bacterial photodamage.

PMID- 14705644
TI  - Mechanisms of selenium-mediated protection from photocarcinogenesis and cell
      death are not solely p53-dependent.
AB  - Recent studies published in Oncogene and Proc. Natl. Acad. Sci. USA ascribe a
      role for selenium, acting through wild type p53, in protecting skin cells in
      culture from ultraviolet radiation-induced death. While selenium clearly protects
      cells against ultraviolet radiation-induced death, data that we present and
      discuss in this letter shows that wild type p53 is not required for such
      protection. Moreover the non-physiologically high levels of selenium used in some
      studies leads us to question the relevance of such effects for selenium-induced
      photoprotection.

PMID- 14705645
TI  - Fractionation of heavy metals in different particle-size sediments and its
      relationship with heavy metal pollution.

PMID- 14705646
TI  - Phytotoxic effects of antifouling compounds on nontarget plant species.

PMID- 14705647
TI  - PCB residues in a breast cancer patient population.

PMID- 14705648
TI  - Development of site specific empirical formula for minimum stack height
      estimation.

PMID- 14705649
TI  - Effect of ascorbic acid on milk lead and cadmium level on subclinical and
      clinical cases of mastitis.

PMID- 14705650
TI  - Occurrence of nitrate and arsenic in alluvium and bolson aquifers of west Texas,
      USA.

PMID- 14705651
TI  - Concentrations of glyphosate and AMPA in sediment following operational
      applications of Rodeo to control smooth cordgrass in Willapa Bay, Washington,
      USA.

PMID- 14705652
TI  - Environmental behavior of the herbicide acetochlor in soil.

PMID- 14705653
TI  - Biodegradation of the herbicides atrazine, cyanazine, and dicamba by methanogenic
      enrichment cultures from selective soils of China.

PMID- 14705654
TI  - Enhanced mineralization of atrazine in compost-amended soil in laboratory
      studies.

PMID- 14705656
TI  - Characteristics of phosphorous components in drainage water.

PMID- 14705655
TI  - Control and amelioration of phosphorus losses from a clay soil heavily manured
      with animal slurries.

PMID- 14705657
TI  - Preliminary study of the clam Ruditapes decussatus exposed in situ to metal
      contamination and originating from the Gulf of Gabes, Tunisia.

PMID- 14705658
TI  - Dechlorination of PCBs in water under UV irradiation and the relationship between
      the electric charge distribution on the carbon atom and the site of
      dechlorination occurrence.

PMID- 14705659
TI  - Effect of methamidophos on sorption-desorption behavior of copper in soils.

PMID- 14705660
TI  - Response to elevated CO2 of Indian mustard and sunflower growing on copper
      contaminated soil.

PMID- 14705661
TI  - Combined toxic effects of cadmium and acid rain on Vicia faba L.

PMID- 14705662
TI  - Effects of simultaneous exposure to atmospheric sulfur dioxide and heavy metals
      on the yield and metal content of soybean grain (Glycine max [L.] Merr.).

PMID- 14705663
TI  - Effects of sewage irrigation on the growth and scavenging system of activated
      oxygen of crop plants.

PMID- 14705664
TI  - Analysis of zinc phosphide in baits, water, soil, and biological specimens.

PMID- 14705665
TI  - Determination of semivolatile compounds in drinking water by tandem mass
      spectrometric detection.

PMID- 14705666
TI  - Comparison of ambient air levels of PCBs and organochlorine pesticides at two
      sites in Zagreb, Croatia.

PMID- 14705667
TI  - Vapor and particle phase determination of polycyclic aromatic hydrocarbons in
      urban air.

PMID- 14705668
TI  - Isolation and identification of extracts of Eichhornia crassipes and their
      allelopathic effects on algae.

PMID- 14705669
TI  - pH maintenance of Chemi-Thermo-Mechanical Pulp mill effluent by CO2 recycling
      during trout lethality testing.

PMID- 14705670
TI  - Comparative toxicity of contaminated sediment from a mining spill using two
      amphipods species: Corophium volutator (Pallas, 1776) and Ampelisca brevicornis
      (A. Costa, 1853).

PMID- 14705671
TI  - pH-stress and toxicity of nitrophenols to Tetrahymena pyriformis.

PMID- 14705672
TI  - Effect of temperatures on zinc accumulation in the Gill, liver, and kidney of
      Oreochromis niloticus (L. 1758).

PMID- 14705673
TI  - Concentrations of metallothionein-like proteins and heavy metals in the
      freshwater snail Lymnaea stagnalis exposed to different levels of waterborne
      cadmium.

PMID- 14705674
TI  - A moment to reflect.

PMID- 14705675
TI  - Advances in neuroanaesthesia.

PMID- 14705676
TI  - The airway.

PMID- 14705677
TI  - Cardiac anaesthesia: the last 10 years.

PMID- 14705678
TI  - Critical care.

PMID- 14705679
TI  - Drugs in anaesthesia.

PMID- 14705680
TI  - Obstetric anaesthesia and analgesia.

PMID- 14705681
TI  - Orthopaedic anaesthesia.

PMID- 14705682
TI  - Paediatric anaesthesia: past, present and future.

PMID- 14705683
TI  - Pain management.

PMID- 14705684
TI  - Regional anaesthesia.

PMID- 14705685
TI  - Who to report to the coroner? A survey of intensive care unit directors and Her
      Majesty's Coroners in England and Wales.
AB  - We performed a postal survey to assess the ability of intensive care unit
      directors and Her Majesty's Coroners to recognise deaths that should be reported
      to the local coroner. The survey questionnaire consisted of 12 hypothetical case
      scenarios. Coroners were significantly better at identifying reportable deaths
      than intensive care unit directors (median correct recognition scores of 11
      (interquartile range 9.25-11) vs. 8 (interquartile range 7-10), respectively, p <
      0.01). Deaths associated with an accident, medical treatments, industrial
      disease, neglect and substance abuse were significantly under-reported by
      intensive care unit directors (p < 0.01). Results show that significant numbers
      of deaths on intensive care units in England and Wales may not be being referred
      for further investigation, and that wide variation in local coroners' practices
      exists. Improvements in postgraduate medicolegal education about deaths
      reportable to a coroner are required. National regulations need to be more
      detailed and standardised so that regional variation is eliminated.

PMID- 14705686
TI  - Anaesthesia for lung volume reduction surgery.
AB  - Lung volume reduction surgery is a surgical treatment for severe emphysema that
      is increasing in popularity. The aim is to reverse the hyperexpansion of the
      lungs that leads to expiratory airflow limitation, compromises the diaphragm and
      chest wall mechanics, and tamponades the right ventricle. Optimal patient
      selection has not yet been established, but it has become clear that those
      patients with the most severe disease have an unacceptably high surgical
      mortality. The anaesthetic management of patients undergoing lung volume
      reduction surgery requires a good understanding of both the pathophysiology of
      the disease and the surgical procedure. It is important for the anaesthetist and
      the surgeon to work closely, supported by a large multidisciplinary team.
      Excellent analgesia is essential to a successful outcome; whether this is best
      provided by thoracic epidural is as yet unclear.

PMID- 14705687
TI  - The road to success: a review of 1000 axillary brachial plexus blocks.
AB  - The authors present their experience of > 1000 axillary brachial plexus blocks
      performed over 13 years (1990-2002). Using a technique that involves the location
      of individual nerves with a nerve stimulator, the overall success rate was 97.9%,
      ranging from 89.7% in 1990 to 98.4% in 1998. There have been no failures, defined
      as the need for conversion to general anaesthesia, in the last 500 blocks.
      Supplementary nerve blocks at the elbow were performed in 22.2% of patients. The
      first author, trained and supervised by the second author, achieved similar
      success rates in half the time taken by the second author. The authors conclude
      that technique and experience are the keys to success, but that high success
      rates can be achieved in a short time if anaesthetists are trained by experts in
      regional anaesthesia.

PMID- 14705688
TI  - A comparison of deep vs. awake removal of the laryngeal mask airway in paediatric
      dental daycase surgery. A randomised controlled trial.
AB  - Dental anaesthesia provides a potential conflict between anaesthetist and surgeon
      because of the shared airway. The laryngeal mask airway (LMA) has helped to
      improve airway control for these procedures, but there is little evidence for
      best practice on the timing of their removal after airway surgery in the
      paediatric population. We compared 'awake' and 'deep' removal of the LMA in 196
      patients aged from 2 to 15 years in a randomised, controlled study. We found that
      average peripheral oxygen saturation (SpO2) was lower in the deep group and this
      was statistically significant (96.2% vs. 94.9%, p = 0.04). It was also found that
      the deep group had a higher incidence of patients with SpO2 < 95% (p = 0.003) and
      of patients who coughed (p = 0.003). We conclude that the LMA should be taken out
      awake in these patients.

PMID- 14705690
TI  - Consent for anaesthesia.

PMID- 14705689
TI  - Effect of postoperative skin-surface warming on oxygen consumption and the
      shivering threshold.
AB  - Cutaneous warming is reportedly an effective treatment for shivering during
      epidural and after general anaesthesia. We quantified the efficacy of cutaneous
      warming as a treatment for shivering. Unwarmed surgical patients (final intra
      operative core temperatures approximately 35 degrees C) were randomly assigned to
      be covered with a blanket (n = 9) or full-body forced-air cover (n = 9).
      Shivering was evaluated clinically and by oxygen consumption. Forced-air heating
      increased mean-skin temperature (mean (SD) 35.7 degrees C (0.4) vs. 33.2 degrees
      C (0.8); p < 0.0001) and lowered core temperature at the shivering threshold
      (35.7 degrees C (0.2) vs. 36.4 degrees C(0.2); p < 0.0001). Active warming
      improved thermal comfort and significantly reduced oxygen consumption from 9.7
      (4.4) ml x min(-1) x kg(-1) to 5.6 (1.9) ml x min(-1) x kg(-1) (p = 0.038).
      However, the duration of shivering was similar in the unwarmed (37 min (11)) and
      active warming (36 min (10)) groups. Core temperature contributed about four
      times as much as skin temperature to control of shivering. Cutaneous warming
      improved thermal comfort and reduced metabolic stress in postoperative patients,
      but did not quickly obliterate shivering.

PMID- 14705691
TI  - Academic anaesthesia.

PMID- 14705692
TI  - Patient safety.

PMID- 14705693
TI  - Underpowered and overbiased? Potentially unfair to the single-use bougie.

PMID- 14705694
TI  - Sleep deprivation and performance.

PMID- 14705695
TI  - Patients ideas of surgical risk.

PMID- 14705696
TI  - Faulty unidirectional expiratory valve as a cause of rebreathing.

PMID- 14705697
TI  - Six Smiths and safety.

PMID- 14705698
TI  - Capnography detects tracheal placement but is it 'correct'?

PMID- 14705699
TI  - A hidden safety feature in the event of oxygen failure.

PMID- 14705700
TI  - Tracheal ring fracture--dislodgement after Blue Rhino percutaneous tracheostomy.

PMID- 14705701
TI  - Fatal cardiac perforation by central venous catheter dilators: does the length
      matter?

PMID- 14705702
TI  - The Negus slotted laryngoscope.

PMID- 14705703
TI  - Something to chew over?

PMID- 14705704
TI  - The ProSeal laryngeal mask airway: an easier and safer approach to tracheal tube/
      laryngeal mask exchange.

PMID- 14705705
TI  - Contraindications to cricoid pressure.

PMID- 14705706
TI  - Incorrect blood results.

PMID- 14705707
TI  - Thrombosis related to emergency factor VIIa treatment.

PMID- 14705708
TI  - Malignant hyperthermia--patients don't always read the textbook.

PMID- 14705709
TI  - Ionised magnesium concentrations in non-neurosurgical patients undergoing spinal
      anaesthesia.

PMID- 14705710
TI  - A novel role for magnesium?

PMID- 14705711
TI  - Diprifusor--things are not always what they seem.

PMID- 14705712
TI  - Pulmonary mechanics and volatile anaesthesia.

PMID- 14705713
TI  - Fetal distress and the 30-minute rule.

PMID- 14705714
TI  - Syntocinon and 'epidurals' in labour--which comes first?

PMID- 14705715
TI  - Ethical considerations in obtaining consent under anaesthesia.

PMID- 14705716
TI  - Whoosh test 2 and confirmation of lumbar epidural space.

PMID- 14705717
TI  - Diagnostic tattoo in a parturient with 'ecstasy' use.

PMID- 14705718
TI  - Case volume and outcome.

PMID- 14705719
TI  - Outcomes after cerebral aneurysm clip occlusion in the United States: the need
      for evidence-based hospital referral.
AB  - OBJECT: In an age of multimodality and multidisciplinary treatment of cerebral
      aneurysms, patient outcomes have improved significantly. For a number of complex
      surgical procedures, hospitals with high case volumes yield superior outcomes.
      The effect of hospital volume on the mortality rate after emergency and elective
      cerebral aneurysm clip occlusion in a nationally representative sample of
      patients is unknown. METHODS: Using clinical data derived from the Nationwide
      Inpatient Sample for the years from 1995 through 1999, 12,023 patients who
      underwent clip occlusion of a cerebral aneurysm (International Classification of
      Diseases, Ninth Revision, Clinical Modification code 3951) were included. Patient
      age, comorbid conditions, nature of admission, and diagnosis of subarachnoid
      hemorrhage were abstracted. Hospital case volume was grouped into quartiles.
      Unadjusted and case-mix adjusted analyses were performed. The mean patient age
      was 53.2 +/- 13.5 years. The overall crude postoperative mortality rates for
      emergency and elective aneurysm clip occlusion were 12.2 and 6.6%, respectively.
      Very low volume hospitals demonstrated higher mortality rates than very high
      volume hospitals for both emergency (14.7 compared with 8.9%, p < 0.001) and
      elective (9.4 compared with 4.5%, p < 0.001) aneurysm surgery. Patient-specific
      predictors of death in the multivariate model were renal disease (odds ratio [OR]
      3.32, p < 0.042); age (> 60 years, OR 2.36, p < 0.001; 51-60 years, OR 1.63, p <
      0.001; 40-50 years, OR 1.25, p = 0.047); chronic obstructive pulmonary disease
      (present, OR 1.52, p < 0.001); and nature of admission (emergency, OR 1.18, p =
      0.03). Provider-specific predictors of death included very low volume (OR 1.59, p
      < 0.001); low-volume (OR 1.37, p = 0.001); and high-volume (OR 1.45, p < 0.001)
      hospitals compared with very high volume hospitals. CONCLUSIONS: A significant
      volume-outcome effect exists for surgical treatment of cerebral aneurysms in the
      US. Factors influencing this effect should be investigated to guide future
      healthcare policy and evidence-based referral. Whenever possible, healthcare
      practitioners should refer patients to centers in which superior outcomes are
      consistently demonstrated.

PMID- 14705720
TI  - No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a
      randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECT: From the moment an intracranial aneurysm ruptures, cerebral blood flow is
      impaired, and this impairment mainly determines the outcome in patients who
      survive after the initial bleeding. The exact mechanism of impairment is unknown,
      but activation of coagulation and fibrinolysis correlate with clinical condition
      and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this
      study was to determine whether enoxaparin, a low-molecular-weight heparin, which
      is a well-known anticoagulating agent, has any effect on the outcome of
      aneurysmal SAH postoperatively. METHODS: In this randomized, double-blind, single
      center clinical trial, 170 patients (85 per group) with aneurysmal SAH were
      randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily)
      or a placebo, starting within 24 hours after occlusion of the aneurysm and
      continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome
      was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales.
      Patients were eligible for the study if surgery was performed within 48 hours
      post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on
      the first postoperative computerized tomography scan. At 3 months, there were no
      significant differences in outcome by treatment group. Of the 170 patients, 11
      (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable
      outcome were poor initial condition, delayed cerebral ischemia, and surgical
      complications. There were four patients with additional intracranial bleeding in
      the group receiving enoxaparin. The bleeding was not necessarily associated with
      the treatment itself, nor did it require treatment, and there were no such
      patients in the placebo group. CONCLUSIONS: Enoxaparin seemed to have no effect
      on the outcome of aneurysmal SAH in patients who had already received routine
      nimodipine and who had received triple-H therapy when needed. Routine use of low
      molecular-weight heparin should be avoided during the early postoperative period
      in patients with SAH, because this agent seems to increase intracranial bleeding
      complications slightly, with no beneficial effect on neurological outcome.

PMID- 14705721
TI  - Multimodal treatment of ruptured dissecting aneurysms of the vertebral artery
      during the acute stage.
AB  - OBJECT: The goal of this study was to implement an algorithm for and assess the
      multimodal (endovascular and microsurgical) treatment of patients with ruptured
      dissecting aneurysms of the vertebral artery (VA) during the acute stage.
      METHODS: During a 4-year period, the authors treated 19 ruptured dissecting
      aneurysms of the VA during the acute stage, within 3 days after the hemorrhage.
      Factors guiding management decisions were tolerance of the test occlusion and the
      site of the dissection. The algorithm takes into account these factors to select
      among treatment options, that is, trapping of the VA with Guglielmi Detachable
      Coils (GDCs); trapping of the VA and revascularization of the posterior inferior
      cerebellar artery (PICA); trapping of the VA and VA-posterior cerebral artery
      (PCA) anastomosis; and trapping of the VA, VA-PCA anastomosis, and
      revascularization of the PICA. Of the 15 aneurysms without PICA involvement, 14
      were treated by trapping of the VA with GDCs and one by trapping of the VA and a
      VA-PCA bypass. The other four aneurysms with PICA involvement were treated by VA
      trapping and PICA revascularization. There was no episode of recurrent hemorrhage
      or ischemia during the posttreatment follow-up period. Although lateral medullary
      syndrome developed as a permanent complication in one patient, a good recovery
      was made by the other 18 patients by 6 months after the ictus. CONCLUSIONS: The
      factors that determine the appropriate treatment for ruptured dissecting
      aneurysms of the VA are tolerance of a test occlusion and the site of dissection.
      Favorable patient outcomes can be achieved when this algorithm is used.

PMID- 14705722
TI  - Delayed hemorrhage following resection of an arteriovenous malformation in the
      brain.
AB  - OBJECT: Between 1989 and 2002 the authors treated 416 cases of angiographically
      confirmed arteriovenous malformations (AVMs) of the brain. METHODS: Three hundred
      fifty-five patients underwent resection of an AVM; 2% died and 12% experienced a
      permanent morbidity (1.7% experienced a deterioration of modified Rankin Scale
      [mRS] score of 3-5). Patient outcomes in this series were based on the Spetzler
      Martin grade. For patients with Grade I and II AVMs the rate of permanent
      morbidity was 1% and the rate of mortality was 0.5%. For patients with Grade III
      AVMs the morbidity rate was 18.9% (2.7% experienced a deterioration of mRS score
      of 3-5) and the mortality rate was 2.7%. For patients with Grade IV and V AVMs
      the morbidity rate was 25.6% (5.1% experienced a deterioration of mRS score of 3
      5) and the mortality rate was 7.7%. No patient with a Spetzler-Martin Grade I or
      II lesion had a worsened outcome due to delayed hemorrhage, whereas 3.6% of
      patients with a Grade III and 12.8% of patients with Grade IV and V AVMs
      experienced delayed hemorrhage that led to a permanent downgrade in function.
      With the introduction of an aggressive postoperative blood pressure protocol (for
      AVMs with grades > II and sizes > 3.5 cm in diameter) the incidence of delayed
      postoperative hemorrhage leading to mortality or permanent morbidity decreased
      from 4.4 to 1%. This difference was significant. Neither case selection nor
      complications other than delayed hemorrhage changed between these two periods.
      CONCLUSIONS: In selected cases an aggressive postoperative blood pressure
      protocol is likely to reduce delayed hemorrhage following AVM resection.

PMID- 14705723
TI  - Urgent endovascular treatment of acute symptomatic occlusion of the cervical
      internal carotid artery.
AB  - OBJECT: The prognosis of patients with acute symptomatic cervical internal
      carotid artery (ICA) occlusion is generally considered to be poor. Traditionally,
      such patients are not considered eligible for urgent thrombolytic/endovascular
      treatment. Since 1998, an aggressive therapeutic approach with endovascular
      treatment has been adopted at the authors' institution. In this report they
      assess whether aggressive treatment of ICA occlusion is appropriate. METHODS: The
      clinical characteristics and outcome of six consecutive patients treated urgently
      with an endovascular approach between 1998 and 2001 are reviewed and summarized.
      Recanalization was accomplished in all patients. At a mean follow-up period of 8
      months (range 2-14 months), five of six patients had good or excellent outcomes
      (modified Rankin Scale [mRS] Score 0-1) and one had a poor outcome (mRS Score 4).
      CONCLUSIONS: With recent advancements in thrombolytic and endovascular
      treatments, an aggressive endovascular approach in patients with acute
      symptomatic cervical ICA occlusion may be successful. Further clinical data are
      required to determine the optimal endovascular approach in these patients.

PMID- 14705724
TI  - Characterization of perioperative seizures and epilepsy following aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECT: The reported incidence, timing, and predictive factors of perioperative
      seizures and epilepsy after subarachnoid hemorrhage (SAH) have differed
      considerably because of a lack of uniform definitions and variable follow-up
      periods. In this study the authors evaluate the incidence, temporal course, and
      predictive factors of perioperative seizures and epilepsy during long-term follow
      up of patients with SAH who underwent surgical treatment. METHODS: Two hundred
      seventeen patients who survived more than 2 years after surgery for ruptured
      intracranial aneurysms were enrolled and retrospectively studied. Episodes were
      categorized into onset seizures (< or = 12 hours of initial hemorrhage),
      preoperative seizures, postoperative seizures, and late epilepsy, according to
      their timing. The mean follow-up time was 78.7 months (range 24-157 months).
      Forty-six patients (21.2%) had at least one seizure post-SAH. Seventeen patients
      (7.8%) had onset seizures, five (2.3%) had preoperative seizures, four (1.8%) had
      postoperative seizures, 21 (9.7%) had at least one seizure episode after the 1st
      week postoperatively, and late epilepsy developed in 15 (6.9%). One (3.8%) of 26
      patients with perioperative seizures (onset, preoperative, or postoperative
      seizure) had late epilepsy at follow up. The mean latency between the operation
      and the onset of late epilepsy was 8.3 months (range 0.3-19 months). Younger age
      (< 40 years old), loss of consciousness of more than 1 hour at ictus, and Fisher
      Grade 3 or greater on computerized tomography scans proved to be significantly
      related to onset seizures. Onset seizure was also a significant predictor of
      persistent neurological deficits (Glasgow Outcome Scale Scores 2-4) at follow up.
      Factors associated with the development of late epilepsy were loss of
      consciousness of more than 1 hour at ictus and persistent postoperative
      neurological deficit. CONCLUSIONS: Although up to one fifth of patients
      experienced seizure(s) after SAH, more than half had seizure(s) during the
      perioperative period. The frequency of late epilepsy in patients with
      perioperative seizures (7.8%) was not significantly higher than those without
      such seizures (6.8%). Perioperative seizures did not recur frequently and were
      not a significant predictor for late epilepsy.

PMID- 14705725
TI  - Enhanced stability of somatosensory evoked potentials attained in the median
      nerve by using temporal electrodes for intraoperative recording in patients in
      the semisitting position.
AB  - OBJECT: Findings published in case reports indicate that monitoring of median
      nerve somatosensory evoked potentials (MN-SSEPs) is unreliable in patients who
      undergo surgery while in the semisitting position due to the occurrence of
      changes in the potentials that are unrelated to neurological damage. The present
      study was designed to test the hypothesis that in these patients MN-SSEPs are
      more stable when recording electrodes are placed over the temporal region.
      METHODS: In 30 patients who underwent surgery in the semisitting position, MN
      SSEPs were recorded intraoperatively by using electrodes placed over the temporal
      region as well as those placed at conventional recording sites. The authors
      analyzed MN-SSEP amplitudes and latencies at different recording sites and at
      distinct steps of the monitoring procedure. In 10 of the 30 patients a clinically
      significant attenuation (> 50%) of MN-SSEP amplitude was observed at conventional
      recording sites and this was obviously not related to neurological damage. In
      contrast, no significant changes were observed in MN-SSEPs recorded from
      electrodes located over the temporal region. CONCLUSIONS: In patients who undergo
      surgery in the semisitting position, the use of additional recording electrodes
      placed over the temporal region makes intraoperative MN-SSEP monitoring less
      prone to false-positive alarms and thus enhances the reliability of
      intraoperative MN-SSEP monitoring.

PMID- 14705726
TI  - Asymmetry of pressure autoregulation after traumatic brain injury.
AB  - OBJECT: The aim of this study was to assess the asymmetry of autoregulation
      between the left and right sides of the brain by using bilateral transcranial
      Doppler ultrasonography in a cohort of patients with head injuries. METHODS:
      Ninety-six patients with head injuries comprised the study population. All
      significant intracranial mass lesions were promptly removed. The patients were
      given medications to induce sedation and paralysis, and artificial ventilation.
      Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in
      an invasive manner. A strategy based on the patient's cerebral perfusion pressure
      (CPP = ABP - ICP) was applied: CPP was maintained at a level higher than 70 mm Hg
      and ICP at a level lower than 25 mm Hg. The left and right middle cerebral
      arteries were insonated daily, and bilateral flow velocities (FVs) were recorded.
      The correlation coefficient between the CPP and FV, termed Mx, was calculated and
      time-averaged over each recording period on both sides. An Mx close to 1
      signified that slow fluctuations in CPP produced synchronized slow changes in FV,
      indicating a defective autoregulation. An Mx close to 0 indicated preserved
      autoregulation. Computerized tomography scans in all patients were reviewed; the
      side on which the major brain lesion was located was noted and the extent of the
      midline shift was determined. Outcome was measured 6 months after discharge. The
      left-right difference in the Mx between the hemispheres was significantly higher
      in patients who died than in those who survived (0.16 +/- 0.04 compared with 0.08
      +/- 0.01; p = 0.04). The left-right difference in the Mx was correlated with a
      midline shift (r = -0.42; p = 0.03). Autoregulation was worse on the side of the
      brain where the lesion was located (p < 0.035). CONCLUSIONS: The left-right
      difference in autoregulation is significantly associated with a fatal outcome.
      Autoregulation in the brain is worse on the side ipsilateral to the lesion and on
      the side of expansion in cases in which there is a midline shift.

PMID- 14705727
TI  - Analysis of taste disturbance before and after surgery in patients with
      vestibular schwannoma.
AB  - OBJECT: The frequency, nature, and history of subjective taste disturbance before
      and after vestibular schwannoma (VS) surgery was investigated. METHODS: Personal
      interviews were conducted in 108 patients with unilateral VS. Abnormalities in
      taste perception, either a significant reduction or a change in character, were
      experienced by 31 patients (28.7%) before surgery and by 37 (34.3%) after tumor
      removal. Preoperative taste disturbance worsened after surgery in five (16.1%) of
      the 31 patients, remained unchanged in eight (25.8%), improved in two (6.5%), and
      became normal in 16 (51.6%). Taste disturbance occurred postoperatively in 22
      (28.6%) of 77 patients who had experienced no preoperative taste disturbance. The
      mean onset of the abnormality after resection was 1.1 +/- 1.7 months.
      Postoperative taste disturbance resolved in 24 of the 37 patients (64.9%) within
      1 year after onset. CONCLUSIONS: Subjective taste disturbance was common before
      and after VS removal, and the natural history of this condition was very variable
      in the pre- and postoperative periods. All patients who undergo surgery for VS
      should receive appropriate counseling about the likelihood and course of
      postoperative complications, including dysfunction of the sensory component of
      the facial nerve.

PMID- 14705728
TI  - A prospective controlled study of sleep respiratory events in patients with
      craniovertebral junction malformation.
AB  - OBJECT: Craniovertebral junction malformation (CVJM) or Chiari malformation in
      adults, with or without syringomyelia and basilar invagination, produces neuronal
      dysfunction of the brainstem, cerebellum, cranial nerves, and upper spinal cord.
      The respiratory center and some of its afferent and efferent components can be
      altered in these diseases. The authors studied patients with and without CVJM to
      determine whether this physical feature contributed to sleep disturbances.
      METHODS: Respiratory manifestations during sleep were studied prospectively, by
      using whole-night polysomnography, in 32 symptomatic patients (CVJM group) and 16
      healthy volunteers (control group). Patients with CVJM presented with more sleep
      disturbances (reports of snoring and apnea) than those in the control group. The
      apnea/hypopnea index values were higher in patients with CVJMs than in the
      control group (13 +/- 15 compared with 3 +/- 6; p = 0.007) and the rate of
      central sleep apneas was higher in the CVJM than in the control group (22 +/- 30
      compared with 4 +/- 8%; p = 0.009). The apnea/hypopnea index was highest in the
      subgroup with basilar invagination than in the other subgroups. The central
      apneic episodes were more frequent in the patients with basilar invagination (35
      +/- 40%; p = 0.001) and in those with syringomyelia (17.6 +/- 24.6%; p = 0.003)
      than in the control group (4 +/- 8%). Patients with symptomatic CVJM, especially
      those with basilar invagination, presented with more sleep respiratory compromise
      than did those in the control group. CONCLUSIONS: The incidence of sleep
      apnea/hypopnea syndrome is significantly higher in patients with CVJM.

PMID- 14705729
TI  - Cerebral metabolic correlates as potential predictors of response to anterior
      cingulotomy for treatment of major depression.
AB  - OBJECT: Neurosurgical procedures are a viable intervention for severe, treatment
      refractory major depression, although they have been associated with only modest
      rates of efficacy. The purpose of this study was to identify possible
      neuroimaging predictors of treatment response to anterior cingulotomy in patients
      with major depression. METHODS: Thirteen patients underwent stereotactic anterior
      cingulotomy for treatment-refractory major depression. Symptom severity was
      measured using the Beck Depression Inventory (BDI) both before and approximately
      12 months after surgery. The authors performed [18F]fluorodeoxyglucose-positron
      emission tomography (PET) studies in all patients preoperatively. Statistical
      parametric mapping methods were used to test for loci of significant correlation
      between preoperative regional cerebral metabolism and postoperative reduction in
      BDI scores. The mean (+/- standard deviation) change in the BDI score from the
      preoperative period (43.7 +/- 7.8) to the postoperative period (30.5 +/- 21.3)
      was 33.1 +/- 45.4%. Two loci--the left subgenual prefrontal cortex and left
      thalamus--were identified as sites at which preoperative metabolism was
      significantly correlated with subsequent improvement in depressive symptom
      severity following cingulotomy. Specifically, higher preoperative rates of
      metabolism at these loci were associated with better postoperative results.
      CONCLUSIONS: Possible PET scanning predictors of treatment response were
      identified in patients with major depression who had undergone anterior
      cingulotomy. Further research will be necessary to determine the reproducibility
      of this finding. If confirmed, the availability of an index for noninvasively
      predicting a patient's response to cingulotomy for the treatment of major
      depression would be of great clinical value.

PMID- 14705730
TI  - Delineating gray and white matter involvement in brain lesions: three-dimensional
      alignment of functional magnetic resonance and diffusion-tensor imaging.
AB  - OBJECT: The role of functional magnetic resonance (fMR) imaging has become
      increasingly important in the presurgical mapping of gray matter. Neurosurgical
      interventions often involve fiber bundles that connect critical functional areas.
      Recently, diffusion-tensor (DT) imaging has enabled the visualization of fiber
      bundle direction and integrity, thus providing the ability to delineate clearly
      white matter from gray matter tissue. The main objective of this study was to
      improve the presurgical assessment of critical functionality in the vicinity of
      brain lesions by combining DT and fMR imaging methodologies. METHODS: Twenty
      patients with various space-occupying brain lesions underwent imaging for
      presurgical evaluation of motor and/or somatosensory functions. The authors focus
      on five patients with diverse space-occupying brain lesions. Diffusion tensor
      based fiber tracking and fMR imaging activation maps were superimposed in three
      dimensions to visualize pyramidal tracts corresponding to motor and somatosensory
      regional activation. CONCLUSIONS: The combination of DT and fMR imaging for
      presurgical functional brain mapping provides valuable information that cannot be
      extracted using either method alone. The validity and sensitivity of noninvasive
      functional mapping for surgical guidance could be improved by considering results
      obtained with both methods. Furthermore, the use of three-dimensional
      visualization seems crucial and unique for viewing and understanding the
      complicated spatial relationship among the lesion, gray matter activation, and
      white matter fiber bundles.

PMID- 14705731
TI  - Microsurgical anatomy of the great cerebral vein of Galen and its tributaries.
AB  - OBJECT: The deep cerebral veins may pose a major obstacle in operative approaches
      to deep-seated lesions, especially in the pineal region where multiple veins
      converge on the great cerebral vein of Galen. Because undesirable sequelae may
      occur from such surgery, the number of veins and branches to be sacrificed during
      these approaches should kept to a minimum. The purpose of this study was to
      examine venous drainage into the vein of Galen with a view to surgical
      approaches. If a vein hampering surgical access must be sacrificed, it can
      therefore be selected according to the smallest draining territory. METHODS: The
      deep cerebral veins and their surrounding neural structures were examined in 50
      cerebral hemispheres from 25 adult cadavers in which the arteries and veins had
      been perfused with red and blue silicone, respectively. Special consideration was
      given to the size and location of drainage of the vein of Galen and its
      tributaries. CONCLUSIONS: When a surgeon approaches the pineal region, several
      veins may hamper the access route. From posterior to anterior, these include the
      following: the superior vermian and the precentral or superior cerebellar veins,
      which drain into the posteroinferior aspect of the vein of Galen; and the tectal
      and pineal veins, which drain into its anterosuperior aspect. The internal
      occipital vein is the main vessel draining into the lateral aspect of the vein of
      Galen. It may be joined by the posterior pericallosal vein, and in that case has
      an extensive territory. To avoid intraoperative venous infarction, it is
      important to use angiography to determine the venous organization before surgery
      and to estimate the permeability and size of the branches of the deep venous
      system.

PMID- 14705732
TI  - Increased invasive capacity of connexin43-overexpressing malignant glioma cells.
AB  - OBJECT: Malignant glioma cells, similar to astrocytes, express connexin43 (Cx43)
      universally but at widely varied levels. Data from previous studies have
      demonstrated that malignant glioma cells form functional gap junction channels
      among themselves as well as with astrocytes and that such a communication has the
      potential to modulate the phenotypic characteristics of astrocytes. Recently, gap
      junctions have been demonstrated to play a role in the invasive phenotype of
      malignant gliomas. In this study, the authors have further investigated the
      motility and invasion ability of Cx43-overexpressing and Cx43-deficient malignant
      glioma cells. METHODS: Using a standard invasion system of a Matrigel transwell
      invasion chamber, the authors found that the number of Cx43-transfected C6 glioma
      cells (C6-Cx43 cells) migrating through the Matrigel-coated membrane was similar
      to that of mock-transfected control cells (C6-mock cells) during the first 24
      hours, but increased significantly thereafter. When these cells were cocultured
      with astrocytes, the number of invading C6-Cx43 cells was more than threefold
      greater than the number of invading C6-mock cells. Results of an in vitro cell
      motility assay also demonstrated that C6-Cx43 cells were more motile and scatter
      active than C6-mock cells. Furthermore, zymographic analysis of MMPs, an
      important determinant in glioma invasion, demonstrated that the amounts of MMP-2
      and MMP-9 in culture medium collected from C6-Cx43 cells were orders of magnitude
      higher than those from C6-mock cells. In addition, BB-94, a synthetic MMP
      inhibitor, significantly inhibited C6-Cx43 cell invasion. CONCLUSIONS: The
      overexpression of gap junction proteins in glioma cells and the intercellular
      communication between tumor and nontumor glia cells may play important roles in
      the facilitation of glioma cell invasion.

PMID- 14705733
TI  - Inhibition of DNA repair for sensitizing resistant glioma cells to temozolomide.
AB  - OBJECT: Temozolomide (TMZ) is a DNA alkylating agent currently used as adjuvant
      treatment for anaplastic astrocytomas. Its use in managing glioblastoma
      multiforme has been halted because of the lack of therapeutic effects due to cell
      resistance. Note that O6-alkylguanine-DNA alkyltranferase (AGT) is a DNA repair
      enzyme that limits the efficacy of TMZ. In this study the authors investigated
      the ability of O6-benzylguanine (BG), an AGT inhibitor, to sensitize a
      glioblastoma cell line resistant to TMZ. METHODS: The effects of TMZ alone (100
      microg) and after exposure to BG (50 microg) were assessed in two glioblastoma
      cell lines, U373-MG and T98G, respectively, sensitive and resistant to TMZ. Cell
      viability was assessed using trypan blue; cell cycle analysis by fluorescence
      activated cell sorter; and apoptosis and autophagy by terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and
      acridine orange staining, respectively. Furthermore, the involvement of an
      autophagy marker, microtubule-associated light chain 3 (LC3), was assessed.
      Temozolomide suppressed the growth of and caused cell cycle arrest in the G2-M
      phase of U373-MG cells but not T98G cells. Exposure to BG prior to TMZ resulted
      in a significant decrease in cell viability as well as cell cycle arrest in the
      G2-M phase in T98G cells (p < 0.05). Although apoptosis was not detected on TUNEL
      staining, programmed cell death Type II (autophagy) was detected after exposure
      to BG and TMZ in T98G cells. CONCLUSIONS: These results indicate that inhibition
      of AGT by BG can render previously resistant glioma cells sensitive to TMZ
      treatment. The mechanism of cell demise following BG-TMZ treatment seems to be
      autophagy and not apoptosis. Combination therapy involving TMZ and an AGT
      inhibitor may be an effective strategy to treat resistant gliomas.

PMID- 14705734
TI  - Reduction of infarct volume and apoptosis by grafting of encapsulated basic
      fibroblast growth factor-secreting cells in a model of middle cerebral artery
      occlusion in rats.
AB  - OBJECT: This study was conducted to evaluate the effects of grafting encapsulated
      basic fibroblast growth factor (bFGF)-secreting cells in rat brains subjected to
      ischemic injury. METHODS: Two cell lines were used for encapsulated grafting in
      this experiment, namely, a bFGF-secreting cell line established by genetic
      manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty
      seven Sprague-Dawley rats were used in this experiment. The animals were divided
      into the following three groups: those receiving grafts of encapsulated bFGF
      secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK
      cells (naive BHK group); and those with no grafts (control group). The authors
      implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF
      and naive BHK groups. Six days after grafting, the host and control animals
      underwent permanent right middle cerebral artery occlusion (MCAO) with an
      intraluminal suture procedure. The infarct volume was evaluated using 2,3,5
      triphenyltetrazolium chloride staining and computerized image analysis 24 hours
      after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      12 hours after MCAO. The authors found that the infarct volume in the BHK-bFGF
      group was reduced by approximately 30% compared with that in the naive BHK and
      control groups. In the ischemic penumbral area, the number of apoptotic cells in
      the BHK-bFGF group was significantly decreased compared with that in the other
      groups. CONCLUSIONS: The grafting of encapsulated BHK bFGF-secreting cells
      protected the brain from ischemic injury. Encapsulation and grafting of
      genetically engineered cells such as bFGF-secreting cells is thus thought to be a
      useful method for protection against cerebral ischemia.

PMID- 14705735
TI  - Repetitive transcranial magnetic stimulation for protection against delayed
      neuronal death induced by transient ischemia.
AB  - OBJECT: Data in the present study demonstrate that repetitive transcranial
      magnetic stimulation (rTMS) induces ischemic tolerance against delayed neuronal
      death (DND) of hippocampal neurons following an otherwise lethal ischemic insult.
      METHODS: Various regimens of rTMS were delivered to adult gerbils at various
      times prior to an episode of ischemia induced by transient (5-minute) bilateral
      common carotid artery (CCA) occlusion. The extent of DND in the CA1 region of the
      hippocampus was assessed quantitatively 7 days after the transient ischemic
      episode. When rTMS was delivered 2 to 5 days prior to bilateral CCA occlusion,
      DND was substantially attenuated; delivery of rTMS 12 to 24 hours prior to
      occlusion induced partial tolerance. In the group of animals that had received
      stimulation 2 days prior to occlusion, neuron density in the CA1 sector was
      significantly higher (three gerbils, 210.33, 86.01% of normal) than in the group
      that experienced ischemia only (three gerbils, 10.66, 4.36% of normal). A similar
      degree of neuron sparing occurred when stimulation was delivered 3, 4, or 5 days
      prior to occlusion. Note that rTMS was effective when it was delivered at
      frequencies of 25 and 50 Hz. Stimulation at 25 Hz for 128 seconds (3200 pulses)
      was more effective than stimulation at 50 Hz for 64 seconds (3200 pulses) or 128
      seconds (6400 pulses), however. CONCLUSIONS: Noninvasive rTMS represents an
      important tool for exploring the mechanisms of ischemic tolerance and preventing
      ischemic neuronal damage.

PMID- 14705736
TI  - Evaluation of a novel propylene oxide-treated collagen material as a dural
      substitute.
AB  - OBJECT: The authors evaluated a new non-cross-linked, propylene oxide-treated,
      acellular collagen matrix for use as a dural substitute in rabbits. They then
      compared this material to a commonly used dural substitute as well as to native
      dura mater used during primary closure. METHODS: Forty-six rabbits were randomly
      assigned to eight groups of five or six rabbits each. These groups differed
      according to the type of closure material that was used during surgery (native
      dura, control dural substitute, or experimental dural substitute) and the
      duration of convalescence. At the end of the experiment, the tightness of the
      duraplasty was assessed in each live rabbit by continuous infusion of fluid into
      the cistema magna until leakage was detected. The animals were killed and each
      specimen was sectioned and studied histologically. The authors found that the
      experimental dural substitute was safe in animals for this application, that it
      held sutures well, and that a watertight closure was usually achieved. There were
      fewer adhesions between the experimental material and neural tissue was less
      likely to adhere to the cranium than the control graft. Histological examination
      showed that the experimental material had slightly more spindle cells and
      vascularity than the control graft. CONCLUSIONS: The experimental graft material
      has several features that make it an attractive candidate for use as a dural
      substitute.

PMID- 14705737
TI  - Successful stent placement for cervical artery dissection associated with the
      Ehlers-Danlos syndrome. Case report and review of the literature.
AB  - This 44-year-old man with Ehlers-Danlos syndrome (EDS) Type IV presented with
      hemiparesis and the Gerstmann syndrome. Left carotid artery (CA) angiography
      revealed a dissecting aneurysm with severe stenosis located in the common CA; the
      lesion was successfully treated with a stent graft. The patient's clinical course
      after endovascular surgery was uneventful, without occurrence of megacolon. The
      literature for spontaneous CA dissection in EDS Type IV cases is reviewed and
      points for investigation and treatment are discussed.

PMID- 14705738
TI  - Clinical application of robotic telemanipulation system in neurosurgery. Case
      report.
AB  - The NeuRobot is a telecontrolled microscopic micromanipulator system designed for
      neurosurgical procedures. The unit houses a three-dimensional endoscope and three
      robot arms that the surgeon operates without direct contact with the patient. The
      authors have successfully performed robotics-assisted neurosurgical procedures by
      using the NeuRobot in a 54-year-old man who had a recurrent atypical meningioma.
      Following the usual preparation of craniotomy and opening of the dura mater, a
      portion of the tumor was removed using the NeuRobot with the aid of microscopic
      observation. No complication related to the use of the NeuRobot was encountered
      and the patient's postoperative course was uneventful. Although various kinds of
      robots have been developed for use in neurosurgery in recent years, a robotic
      telemanipulation system capable of performing several surgical tasks has not
      previously been introduced to clinical neurosurgery. This is the first case
      report in which neurosurgical manipulation by a robotics system is described.

PMID- 14705739
TI  - Hemangiopericytoma of the confluence of sinuses and the transverse sinuses. Case
      report.
AB  - The authors describe the case of a 38-year-old man with progressive headache and
      blurred vision related to a hemangiopericytoma located exclusively in the
      confluence of sinuses (CoS) and in the transverse sinuses bilaterally. They
      believe this is the first report in which a hemangiopericytoma of the dural
      sinuses has been described without any intradural component. Although the
      diagnosis was not suspected preoperatively, a gross-total resection of the tumor
      with restoration of sinus patency was achieved to relieve the symptoms. This
      diagnosis should be included in the preoperative differential diagnosis of a
      tumor of the CoS. Successful resection can be achieved in these cases.

PMID- 14705740
TI  - Intracranial follicular dendritic cell sarcoma. Case report.
AB  - Intracranial occurrence of follicular dendritic cell (FDC) sarcoma, a rare tumor
      derived from dendritic cells of the lymphoid follicle, has not yet been
      described. Therefore, the case of a 53-year-old man presenting with an
      intracranial mass invading the clivus is reported. The diagnosis of FDC sarcoma
      was confirmed by immunohistochemical staining for dendritic cell markers, that
      is, CD21, CD23, and CD35. Due to some similarities with meningioma, intracranial
      FDC sarcoma might be an underdiagnosed disease.

PMID- 14705741
TI  - Healing of a brain abscess by secondary intention. Case report.
AB  - A cerebral abscess developed in this 33-year-old man after a compound, comminuted
      skull fracture of the left temporoparietal region. This lesion failed to respond
      to standard management, which included subtotal excision and drainage. This case
      presented the unusual opportunity to externalize a cerebral abscess that had
      failed to respond to standard surgical treatment. The cerebral abscess healed
      rapidly by secondary intention. This may be a safe and effective option for an
      abscess that is walled off by granulation tissue and situated close to the
      cortical surface.

PMID- 14705742
TI  - Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable
      Tourette syndrome. Report of three cases.
AB  - Based on the results of thalamotomies described by Hassler in 1970, the authors
      performed bilateral thalamic high-frequency stimulation (HFS) in three patients
      with intractable Tourette syndrome (TS). In this report they describe the long
      term effects. Three male patients (42, 28, and 45 years of age) had manifested
      motor and vocal tics since early childhood. The diagnosis of TS was made
      according to the criteria of the Tourette Syndrome Classification Study Group.
      Any drug or alternative treatment had been either ineffective or only temporarily
      effective in all three patients. There was no serious comorbidity. The target for
      stimulation was chosen at the level of the centromedian nucleus, substantia
      periventricularis, and nucleus ventrooralis internus. After 2 weeks of test
      stimulation, the pulse generators were implanted. After a follow-up period of 5
      years in the patient in Case 1, 1 year in the patient in Case 2, and 8 months in
      the patient in Case 3, all major motor and vocal tics had disappeared and no
      serious complications had occurred. When stimulation was applied at the voltage
      necessary to achieve an optimal result on the tics, a slight sedative effect was
      noted in all three patients. In the patients in Cases 1 and 3 there were
      stimulation-induced changes in sexual behavior. Chronic thalamic HFS may be an
      effective and safe treatment for medically intractable TS in adult patients.
      Unwanted stimulation-induced side effects may occur.

PMID- 14705743
TI  - Anomalous origin of the left A1 segment from the right internal carotid artery.
      Case illustration.

PMID- 14705744
TI  - Treatment of aneurysms with wires and electricity: a historical overview.
AB  - Endovascular treatment of aneurysms has only recently become an accepted
      therapeutic modality. Nonetheless, treatment of aneurysms with the aid of various
      foreign bodies such as needle and wire insertion with or without electrical
      current has been reported since the first half of the 19th century. In 1832
      Phillips induced clot formation in the femoral and carotid arteries of dogs by
      leaving needles in the arteries for variable lengths of time. Simultaneously, in
      France, Velpeau had proposed using "l'acupuncture des arteres dans le traitement
      des anevrismes." Later, Phillips and Pelrequin connected the offending needles to
      a source of electrical current in an attempt to increase thrombus formation and
      aneurysm occlusion. Subsequently, Moore introduced the concept of packing the
      aneurysm with wire inserted through a needle transfixed to the vessel wall. To
      this method, Corradi added electrical current. Widely known as the Moore-Corradi
      technique, it was used in ensuing years with variable success. The early phase of
      endovascular aneurysm treatment culminated when Blakemore and Moore treated a
      case of symptomatic cavernous sinus aneurysm by passing wire through the
      patient's orbit. These pioneering cases combined with technological advances in
      the diagnosis of intracranial aneurysms paved the way for further refinements in
      coil embolization of aneurysms.

PMID- 14705745
TI  - Hyperoxia.

PMID- 14705746
TI  - Hyperoxia.

PMID- 14705747
TI  - Psychosurgery.

PMID- 14705748
TI  - Aneurysm clips.

PMID- 14705749
TI  - Brainstem cavernomas.

PMID- 14705750
TI  - Neurogenic hypertension.

PMID- 14705751
TI  - The ecology of medical care for children in the United States: a new application
      of an old model reveals inequities that can be corrected.

PMID- 14705752
TI  - Maggot debridement therapy for diabetic necrotic foot.

PMID- 14705753
TI  - Decreasing the morbidity, mortality, and cost of stroke through awareness and
      prevention.

PMID- 14705754
TI  - Clinical inquiries from the Family Practice Inquiries Network.

PMID- 14705755
TI  - The growing mandate for clinical preventive medicine.

PMID- 14705756
TI  - Stroke: strategies for primary prevention.
AB  - Stroke is a leading cause of morbidity and mortality in North America. Primary
      prevention of stroke includes lifestyle modifications and measures to control
      blood pressure, cholesterol levels, diabetes mellitus, and atrial fibrillation.
      Lowering blood pressure in patients with hypertension prevents both hemorrhagic
      and ischemic stroke (relative risk reduction, 35 to 45 percent). Observational
      studies suggest that higher cholesterol levels are associated with an increased
      risk of ischemic stroke, and treatment with statins (3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors) may reduce the risk of fatal and nonfatal stroke
      by 25 percent. Although high-quality evidence linking tighter glucose control
      with stroke reduction is lacking, good glucose control and aggressive treatment
      of hypertension and hyperlipidemia in patients with diabetes mellitus are
      recommended. The risk of stroke in patients with atrial fibrillation and the role
      of anticoagulation depend on factors such as age and the presence of comorbid
      conditions. Controversy exists about the roles of angiotensin-converting enzyme
      inhibitors and aspirin in the primary prevention of stroke.

PMID- 14705757
TI  - Information from your family doctor. How to prevent a stroke.

PMID- 14705758
TI  - Orthostatic hypotension.
AB  - Orthostatic hypotension is a physical finding defined by the American Autonomic
      Society and the American Academy of Neurology as a systolic blood pressure
      decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least
      10 mm Hg within three minutes of standing. The condition, which may be
      symptomatic or asymptomatic, is encountered commonly in family medicine. In
      healthy persons, muscle contraction increases venous return of blood to the heart
      through one-way valves that prevent blood from pooling in dependent parts of the
      body. The autonomic nervous system responds to changes in position by
      constricting veins and arteries and increasing heart rate and cardiac
      contractility. When these mechanisms are faulty or if the patient is hypovolemic,
      orthostatic hypotension may occur. In persons with orthostatic hypotension,
      gravitational opposition to venous return causes a decrease in blood pressure and
      threatens cerebral ischemia. Several potential causes of orthostatic hypotension
      include medications; non-neurogenic causes such as impaired venous return,
      hypovolemia, and cardiac insufficiency; and neurogenic causes such as multisystem
      atrophy and diabetic neuropathy. Treatment generally is aimed at the underlying
      cause, and a variety of pharmacologic or nonpharmacologic treatments may relieve
      symptoms.

PMID- 14705759
TI  - Diagnosis and management of post-traumatic stress disorder.
AB  - Although post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder
      that may cause significant distress and increased use of health resources, the
      condition often goes undiagnosed. The lifetime prevalence of PTSD in the United
      States is 8 to 9 percent, and approximately 25 to 30 percent of victims of
      significant trauma develop PTSD. The emotional and physical symptoms of PTSD
      occur in three clusters: re-experiencing the trauma, marked avoidance of usual
      activities, and increased symptoms of arousal. Before a diagnosis of PTSD can be
      made, the patient's symptoms must significantly disrupt normal activities and
      last for more than one month. Approximately 80 percent of patients with PTSD have
      at least one comorbid psychiatric disorder. The most common comorbid disorders
      include depression, alcohol and drug abuse, and other anxiety disorders.
      Treatment relies on a multidimensional approach, including supportive patient
      education, cognitive behavior therapy, and psychopharmacology. Selective
      serotonin reuptake inhibitors are the mainstay of pharmacologic treatment.

PMID- 14705760
TI  - Information from your family doctor. What you should know about post-traumatic
      stress disorder.

PMID- 14705761
TI  - Evaluation and management of toe fractures.
AB  - Fractures of the toe are one of the most common lower extremity fractures
      diagnosed by family physicians. Toe fractures most frequently are caused by a
      crushing injury or axial force such as stubbing a toe. Joint hyperextension and
      stress fractures are less common. Most patients have point tenderness at the
      fracture site or pain with gentle axial loading of the digit. Anteroposterior and
      oblique radiographs generally are most useful for identifying fractures,
      determining displacement, and evaluating adjacent phalanges and digits. Referral
      is indicated in patients with circulatory compromise, open fractures, significant
      soft tissue injury, fracture-dislocations, displaced intra-articular fractures,
      or fractures of the first toe that are unstable or involve more than 25 percent
      of the joint surface. Most children with fractures of the physis should be
      referred, but children with selected nondisplaced Salter-Harris types I and II
      fractures may be treated by family physicians. Stable, nondisplaced toe fractures
      should be treated with buddy taping and a rigid-sole shoe to limit joint
      movement. Displaced fractures of the lesser toes should be treated with reduction
      and buddy taping. Patients with displaced fractures of the first toe often
      require referral for stabilization of the reduction.

PMID- 14705762
TI  - Routine vitamin supplementation to prevent cancer and cardiovascular disease:
      recommendations and rationale.

PMID- 14705763
TI  - Adefovir (Hepsera) for chronic hepatitis B infection.

PMID- 14705764
TI  - Photo quiz. Headache.

PMID- 14705765
TI  - Is fluoxetine an effective therapy for weight loss in obese patients?

PMID- 14705766
TI  - The 2004 Recommended Adult Immunization Schedule.

PMID- 14705767
TI  - Elevated tissue kallikrein activity in airway secretions from patients with
      tracheobronchitis associated with prolonged mechanical ventilation.
AB  - The clinical course of patients undergoing prolonged mechanical ventilation is
      often complicated by the development of purulent tracheobronchitis. The purpose
      of this study was to assess whether ventilator-associated hypersecretion is
      associated with elevated levels of tissue kallikrein (TK) activity. TK can induce
      marked bronchial inflammation in animal models and TK activity is increased in
      the airway secretions of symptomatic asthmatics. It has not been studied in
      conditions with predominantly neutrophilic bronchial secretions, although animal
      data indicate that neutrophil elastase may stimulate TK activity. We measured TK
      activity in airway secretions of patients undergoing mechanical ventilation for
      more than 4 weeks (PMV group) and in two comparator groups: patients with cystic
      fibrosis, who were colonized with Pseudomonas aeruginosa (CF group) and patients
      undergoing mechanical ventilation for less than one week who did not have
      clinical evidence of purulent airway secretions (acute mechanical ventilation,
      AMV group). We also compared the level of neutrophil elastase (NE) activity, an
      index of neutrophil activation, in the three patient groups. TK and NE activity
      in the sol phase were measured by the degradation of chromogenic substrates (DL
      Val-Leu-Arg pNA and N-Methoxy Succinyl Ala-Ala-Pro-Val pNA, respectively).
      Intergroup differences in cell counts were not significant. However, TK activity
      was significantly less in the AMV group than in the PMV and cystic fibrosis
      patients (Kruskal-Wallis ANOVA, p < 0.05). Elastase activity was significantly
      greater in the CF group (p < 0.05) than in the other two groups. Compared to
      patients undergoing short-term mechanical ventilation (AMV group), TK activity
      was elevated in patients with purulent tracheobronchitis associated with
      prolonged mechanical ventilation (PMV group). The elevation in TK activity in
      these patients is comparable to levels in sputum from patients with cystic
      fibrosis (CF group), although the latter had a significantly higher level of NE
      activity. The observation of increased TK activity in patients with neutrophilic
      airway inflammation suggests that TK may play a role in modulating inflammation
      in ventilator-associated tracheobronchitis and may be worthy of further study to
      determine its source and significance.

PMID- 14705768
TI  - Investigation of c-myc and p53 gene alterations in the tumor and surgical
      borderline tissues of NSCLC and effects on clinicopathologic behavior: by the
      FISH technique.
AB  - Genetic alterations on the primary tumoral tissues and surgical borderline
      tissues of 51 patients with NSCLC on which radiotherapy and chemotherapy had not
      been performed were analyzed by using the FISH method with locus-specific probes
      for p53 tumor suppressor gene and c-myc oncogene and centromere-specific probes
      for chromosome 17 and chromosome 8 on which these genes are located. P53
      deletions were detected in 7 patients (13.7%), c-myc amplification in 4 patients
      (7.8%), monosomy 17 in 2 patients (3.9%) and trisomy 8 in 3 patients (5.8%), and
      a high level of polyploidy in tumoral tissues of 6 patients (11.7%). P53 deletion
      and c-myc amplification were found at surgical borderlines of 2 patients and 1
      patient, respectively. Although both p53 deletion and c-myc amplification have
      low frequency at surgical border tissues, not only their detection is important
      for the follow-up of recurrency and metastasis, but it is also important for
      genetical and pathological staging. The results of this study show that c-myc
      amplification in NSCLC is related to the shortening of survival (p < 0.01). C-myc
      amplification and p53 deletion are also effective for the occurrence of
      metastasis (p < 0.05) and the effect of c-myc amplification in this matter is
      much higher than p53 deletion. The gain or loss of copy number of chromosome 8
      and monosomy 17 show parallel effects with c-myc amplification and p53 deletion,
      respectively, on the clinicopathological behavior of tumors.

PMID- 14705769
TI  - Serum vascular endothelial growth factor as a possible prognostic indicator in
      sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disorder of unknown etiology, which
      involves the lung, eye, liver, and other organs. Vascular endothelial growth
      factor (VEGF) is a major regulator of angiogenesis involved in an important role
      in the development of granuloma. However, only a limited number of studies have
      reported on the relationship between serum VEGF values and the clinical status of
      sarcoidosis. Concentrations of serum VEGF were determined in 33 patients with
      sarcoidosis. We investigated the correlation between serum VEGF values and extent
      of disease, prognosis, and radiographic stage compared with serum angiotensin
      converting enzyme (ACE) values as another candidate. Concentrations of serum VEGF
      in patients who received corticosteroid treatment were significantly higher than
      those of patients with spontaneous remission (p < 0.05). In addition, serum VEGF
      values in patients with extrathoracic involvements were significantly higher than
      those of patients with sarcoid lesions limited to the thoracic space (p < 0.05),
      accompanied by a tendency to increase the number of organs involved. The values
      of serum ACE revealed no relationship to the values of serum VEGF, administration
      of corticosteroid, or extrathoracic involvements. We concluded that serum VEGF
      values in patients with sarcoidosis is a predictive factor in determining
      extrathoracic organ involvements and as a parameter for deciding the necessity of
      treatment with corticosteroid. Serum VEGF might be a useful marker as a
      prognostic indicator in sarcoidosis.

PMID- 14705770
TI  - Comparing the relationship of Taxol-based chemotherapy response with P
      glycoprotein and lung resistance-related protein expression in non-small cell
      lung cancer.
AB  - Our aim was to compare Taxol-based chemotherapy response of non-small cell lung
      cancer (NSCLC) with P-glycoprotein (Pgp) or lung resistance protein expression
      (LRP). Immunohistochemical analyses were performed on multiple nonconsecutive
      sections of the biopsy specimens to detect Pgp and LPR expressions in 40 patients
      with advanced NSCLC before Taxol-based chemotherapy. The chemotherapy response
      was evaluated by clinical and radiological methods in the third month after
      completion of treatment. No significant differences of prognostic factors (age,
      sex, body weight loss, performance status, tumor size, tumor stage, and tumor
      cell type) were found between the 20 patients with good and the 20 patients with
      poor responses. The incidence difference of positive Pgp expressions between good
      and poor responses was significant, however, the difference of LRP expression was
      not. We concluded that Taxol-based chemotherapy response of patients with NSCLC
      was related to Pgp but not LPR expression.

PMID- 14705771
TI  - Zonation of ciliated cells on the epithelium of the rat trachea.
AB  - We have used scanning electron microscopy (SEM) to screen the entire epithelial
      surface of the cervical trachea of the adult rat. This scrutiny revealed that the
      density of ciliated cells along this epithelium follows a repetitive pattern:
      circular strips of high density of ciliated cells alternate with areas of low
      density of the same cells. Cilia-poor strips of the tracheal epithelium were seen
      on areas of cartilage rings; here, ciliated cells made up 32% of the total
      surface of the tracheal lining. Cilia-rich areas filled the epithelial surface at
      the tracheal ligaments (i.e., the regions located in-between the rings); here,
      ciliated cells occupied 65% of the tracheal lumen. In the cilia-poor zones, the
      density of ciliated cells decreased from its periphery into its center, where
      cilia were virtually absent. No differences in this pattern of the tracheal
      epithelium were seen between young adult and older rats. We conclude that the
      respiratory epithelium expresses density zonation of ciliated cells on the
      trachea of adult rats. We propose that the high concentration of ciliated cells
      on the regions of epithelium located at the tracheal ligaments suggests that
      these zones are electively committed in the clearance of the respiratory airway.

PMID- 14705772
TI  - Simultaneously evaluating the effects of one-week fluticasone propionate
      inhalation therapy on lung ventilation and permeability in children with asthma.
AB  - This study evaluated the effects of fluticasone propionate inhalation therapy on
      lung ventilation and alveolar permeability by quantitative Tc-99m DTPA
      radioaerosol inhalation lung scintigraphy in 15 children with asthma. Lung
      ventilation was evaluated as the distribution percentage (D%) of Tc-99m DTPA
      radioaerosols in the central, intermediate and peripheral regions of the right
      lung. Alveolar permeability was measured by the rate of Tc-99m DTPA radioaerosol
      clearance curve from the peripheral alveoli of the right lung and represented as
      slope. The D% and slopes were calculated before and after one-week inhalation
      therapy (100 microg fluticasone propionate two times daily for one-week) to
      evaluate the effects of inhalation therapy on lung ventilation and alveolar
      permeability. The preliminary results revealed statistically significantly
      improved lung ventilation but no significant change of alveolar permeability in
      the right lung after one-week fluticasone propionate inhalation therapy in
      children with asthma. We suggest that the widely available and noninvasive Tc-99m
      DTPA radioaerosol inhalation lung scintigraphy can simultaneously evaluate lung
      ventilation and alveolar permeability in one study and should contribute to any
      disorder involving both alveoli and airways.

PMID- 14705773
TI  - Pulmonary function abnormalities associated with exposure to automobile exhaust
      in a diesel bus garage and roads.
AB  - In Kolkata city the road transports are maintained by private and Government
      organization. A major work force belonged to the State Transport Corporation
      (KSTC), Government of West-Bengal. The pollution caused by these vehicles affects
      the workers health and caused different types of respiratory problems. This study
      was undertaken to assess the pulmonary function status of these workers. City
      KSTC garage workers were investigated and categorically divided into two group:
      garage mechanics and the (2) those transporting the passengers (drivers and
      conductors). Vital capacity (VC), forced vital capacity (FVC) and peak expiratory
      flow rate (PEFR) were recorded by Spirovit-SP-10 (Schiller Ltd, Switzerland) and
      Wright's Peak Flow Meter (UK) on 236 workers. The different flow volumes, FEV(1),
      FEV(1%), and flow rates, FEF(02-121), FEF(25-75%), etc. were calculated. The
      administrative people had higher PFT than the other categories. Drivers and
      conductors have almost equal mean PFT values but mechanical workers had slightly
      higher. PFT values according to different age ranges and duration of exposure
      showed gradual decrement as age and duration of exposure increased. Non-smokers
      had higher lung volumes compared to smokers and ex-smokers. Restrictive,
      obstructive and combined types of impairments were noticed in 28.4%, 1.7% and
      2.9%, respectively, workers. The restrictive impairment was found to be 30.4% in
      conductors; 28.9% in drivers, 27.9% in mechanics and 21.7% in administration
      people. Obstructive type of impairment was found to be 2.9% in both drivers and
      conductors. The effect of pollution by dust and fumes may be responsible for
      these pulmonary function impairments, restrictive impairments being greater.

PMID- 14705774
TI  - Quantification of hepatic carbohydrate metabolism in conscious mice using serial
      blood and urine spots.
AB  - In vivo studies of hepatic carbohydrate metabolism in (genetically modified)
      conscious mice are hampered by limitations of blood and urine sample sizes. We
      developed and validated methods to quantify stable isotope dilution and
      incorporation in small blood and urine samples spotted onto filter paper. Blood
      glucose and urinary paracetamol-glucuronic acid were extracted from filter paper
      spots reproducibly and with high yield. Fractional isotopomer distributions of
      glucose and paracetamol-glucuronic acid when extracted from filter paper spots
      were almost identical to those isolated from the original body fluids. Rates of
      infusion of labeled compounds could be adjusted without perturbing hepatic
      glucose metabolism. This approach was used in mice to find the optimal metabolic
      condition for the study of hepatic carbohydrate metabolism. In fed mice, no
      isotopic steady state was observed during a 6-h label-infusion experiment. In 9-h
      fasted mice, isotopic steady state was reached after 3 h of label infusion and
      important parameters in hepatic glucose metabolism could be calculated. The rate
      of de novo glucose-6-phosphate synthesis was 143 +/- 17 micromol kg(-1) min(-1)
      and partitioning to plasma glucose was 79.0 +/- 5.2%. In 24-h-fasted mice, abrupt
      changes were noticed in whole body and in hepatic glucose metabolism at the end
      of the experiment.

PMID- 14705775
TI  - Functionalized self-assembled monolayer on gold for detection of human
      mitochondrial tRNA gene mutations.
AB  - We developed a rapid and simple method to identify single-nucleotide
      polymorphisms (SNPs) in the human mitochondrial tRNA genes. This method is based
      on a universal, functionalized, self-assembled monolayer, XNA on Gold chip
      platform. A set of probes sharing a given allele-specific sequence with a single
      base substitution near the middle of the sequence was immobilized on chips and
      the chips were then hybridized with fluorescence-labeled reference targets
      produced by asymmetric polymerase chain reaction from patient DNA. The ratio of
      the hybridization signals from the reference and test targets with each probe was
      then calculated. A ratio of above 3 indicates the presence of a wild-type
      sequence and a ratio of below 0.3 indicates a mutant sequence. We tested the
      sensitivity of the chip for known mutations in tRNA(Leu(UUR)) and tRNA(Lys) genes
      and found that it can also be used to discriminate multiple mutations and
      heteroplasmy, two typical features of human mitochondrial DNA. The XNA on Gold
      biochip method is a simple and rapid microarray method that can be used to test
      rapidly and reliably any SNP in the mitochondrial genome or elsewhere. It will be
      particularly useful for detecting SNPs associated with human diseases.

PMID- 14705776
TI  - Purification, analysis, and preservation of reduced nicotinamide adenine
      dinucleotide 2'-phosphate.
AB  - Nicotinamide-containing cofactors are ubiquitous in biological systems.
      Consequently, numerous assays have been developed to study such systems that
      involve a variety of derivatives and isotopically labeled forms of these
      cofactors. Often the nicotinamide ring is labeled at the C-4 position which is
      directly involved in the hydride transfer chemistry catalyzed by nicotinamide
      dependent enzymes. A label remote from the reactive center is often also required
      to follow the course of a reaction or the location of the cofactor. Since the
      necessary labeling pattern can be as unique as the designed experiment, these
      cofactors need to be synthesized, analyzed, and, most preferably, preserved. The
      micro-scale preservation of reduced nicotinamides has long been a challenge due
      to the inherent lability of the reduced cofactors. Furthermore, it has been found
      that the reduced 2'-phosphorylated cofactor is even less stable (i.e., reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) is more labile than reduced
      nicotinamide adenine dinucleotide). Presented here are methods that were
      established to purify nicotinamide cofactors via reverse-phase high-performance
      liquid chromatography (HPLC) and, most importantly, to stabilize NADPH under
      optimal conditions for long-term storage. Additionally, an analytical HPLC method
      which achieves 7-min resolution between oxidized and reduced cofactors was
      developed. This method also results in over 4-min resolution of these
      nicotinamide cofactors from various derivatives of folic acid. This analysis
      affords a new analytical assay for the dihydrofolate reductase-catalyzed reaction
      and several dehydrogenases involved in folic acid metabolism.

PMID- 14705777
TI  - A fluorescence-based high-throughput screening assay for inhibitors of human
      immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H
      activity.
AB  - A fluorescence resonance energy transfer assay readily applicable to 96-well and
      384-well microplate formats with robotic operation was developed to enable high
      throughput screening for inhibitors of human immunodeficiency virus-1 (HIV-1)
      reverse transcriptase (RT)-associated RNase H activity, an underexplored target
      for antiretroviral development. The assay substrate is an 18-nucleotide 3'
      fluorescein-labeled RNA annealed to a complementary 18-nucleotide 5'-Dabcyl
      modified DNA. The intact duplex has an extremely low background fluorescent
      signal and provides up to 50-fold fluorescent signal enhancement following
      hydrolysis. The size and sequence of the duplex are such that HIV-1 RT-RNase H
      cuts the RNA strand close to the 3' end. The fluorescein-labeled ribonucleotide
      fragment readily dissociates from the complementary DNA at room temperature with
      immediate generation of a fluorescent signal. This assay is rapid, inexpensive,
      and robust, providing Z' factors of 0.8 and coefficients of variation of about
      5%. The assay can be carried out both in real-time (continuous) and in "quench"
      modes; the latter requires only two addition steps with no washing and is thus
      suitable for robotic operation. Several chemical libraries totaling more than
      106,000 compounds were screened with this assay in approximately 1 month.

PMID- 14705778
TI  - A novel Escherichia coli strain allows functional analysis of guanylate kinase
      drug resistance and sensitivity.
AB  - Guanylate kinase is a critical enzyme in the biosynthesis of guanosine 5'
      triphosphate (GTP) and dGTP and is responsible for the phosphorylation of
      guanosine 5'-monophosphate (GMP) and dGMP to guanosine 5'-diphosphate (GDP) and
      dGDP, respectively. As with many nucleotide-metabolizing enzymes, guanylate
      kinase is involved in antimicrobial and antineoplastic drug activation. This is
      due to the structural similarities of such agents with nucleobases or nucleosides
      that are acted upon by endogenous enzymes. Despite the involvement of guanylate
      kinase in 6-thioguanine, mercaptopurine, and abasic guanosine analog (e.g.,
      ganciclovir) activation, studies have only recently focused on the molecular
      basis of the structure to function relationship of a mammalian guanylate kinase.
      As a means to evaluate the details of amino acid side chain involvement in
      substrate interaction, we have constructed a conditional guanylate-kinase
      deficient Escherichia coli strain that requires the presence of a functional,
      plasmid-borne guanylate kinase for growth under selective conditions. Positive
      genetic selection provides a rapid mechanism to identify not only functional
      guanylate kinase mutants but also those that result in drug resistance. This
      novel strain will be beneficial to assess the role of specific amino acids of
      guanylate kinase in structure, function, drug activation, and drug resistance.

PMID- 14705779
TI  - Fluorometric quantification of RNA and DNA in solutions containing both nucleic
      acids.
AB  - A fluorescence-based method for quantitative determination of RNA and DNA in
      probes containing both nucleic acids has been developed. The total concentration
      of nucleic acids is determined using SYBR Green II dye under conditions providing
      independent binding of the fluorophore with DNA and RNA. The concentration of DNA
      is specifically measured using the Hoechst 33258 dye and the RNA concentration is
      calculated from these data. The procedure allows for accurate determination of
      DNA concentration in the range 10-1000 ng/ml in the presence of 200-fold excess
      of RNA and determination of RNA concentrations in the range 10-1000 ng/ml in the
      presence of large excess of DNA. An absence of the treatment of mixed samples
      with RNase-free DNase I provides rapid, reproducible, and accurate RNA
      quantification.

PMID- 14705780
TI  - Single-sample preparation for simultaneous cellular redox and energy state
      determination.
AB  - A simple and reliable method for the preparation of biological samples for the
      evaluation of biochemical parameters representative of the redox and energy
      states, such as glutathione (GSH), oxidized glutathione (GSSG), oxidized
      nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine
      dinucleotide (NADH), oxidized nicotinamide adenine dinucleotide phosphate
      (NADP+), reduced nicotinamide adenine dinucleotide phosphate (NADPH), coenzyme A
      (CoASH), oxidized CoASH, ascorbate, malondialdehyde, oxypurines, nucleosides, and
      energy metabolites, is presented. Fast deproteinization under nonoxidizing
      conditions is obtained by tissue homogenization in ice-cold, nitrogen-saturated
      CH3CN + 10 mM KH2PO4 (3:1; v:v), pH 7.40. After sample centrifugation to pellet
      precipitated proteins, organic solvent removal is performed on clear supernatants
      by three washings with large volumes of high-performance liquid chromatography
      (HPLC)-grade chloroform. The remaining aqueous phase, free of solvent and any
      lipid-soluble substances that may interfere with the further metabolite analysis,
      is used for the simultaneous ion-pairing HPLC determination of 39 compounds by
      means of a Kromasil C-18, 250 x 4.6-mm, 5-microm-particle-size column with
      tetrabutylammonium hydroxide as the pairing reagent. Results obtained by using
      the present method to prepare different rat tissue extracts demonstrate that it
      is possible to perform a single tissue preparation only for monitoring, in the
      same sample, compounds representative of the redox state (through the direct
      determination of GSH, GSSG, NAD+, NADH, NADP+, NADPH, CoASH, and oxidized CoASH)
      and of the cell energy state (by the analysis of oxypurines, nucleosides, and
      energy metabolites). Applicability of this sample processing procedure to
      quantify variations of the aforementioned compounds under pathological conditions
      was effected in rats subjected to moderate closed-head trauma.

PMID- 14705781
TI  - A continuous fluorimetric assay for aminopeptidase P detailed analysis of product
      inhibition.
AB  - Aminopeptidase P (APP; EC 3.4.11.9) is a proline-specific peptidase hydrolyzing N
      terminal Xaa-Pro peptide bonds. On the basis of its unique substrate specificity
      it is difficult to determine enzyme activity and to estimate potential enzyme
      inhibitors. In this report, we describe the synthesis of a new fluorogenic
      substrate to assay APP. The substrate was characterized using Escherichia coli
      APP and rat intestine APP. The compound contains the fluorogenic 2-aminobenzoyl
      residue and 4-nitroanilide as internal quencher. Both enzymes hydrolyze the
      substrate Lys(N(epsilon)-2-aminobenzoyl)-Pro-Pro-4-nitroanilide at the Lys-Pro
      peptide bond with Km values in the micromolar range. Lys(N(epsilon)-2
      aminobenzoyl)-Pro-Pro-4-nitroanilide is the best substrate of APP from rat
      intestine that is known with a Km value of 3.54 microM and a second-order rate
      constant of 1,142,000 M(-1) s(-1). Unfortunately, product inhibition occurs.
      Inhibition studies using the hydrolysis product Pro-Pro-4-nitroanilide
      demonstrate a linear mixed-type mechanism with a K(i) value of 20.8 microM and an
      alpha value of 5.1 for rat APP and a K(i) value of 76.1 microM and an alpha value
      of 0.4 for E. coli APP, respectively. Furthermore, the hydrolysis of the
      fluorogenic APP substrate catalyzed by prolyl oligopeptidase was investigated.

PMID- 14705782
TI  - Analysis of the stability of amino acids derivatized with naphthalene-2,3
      dicarboxaldehyde using high-performance liquid chromatography and mass
      spectrometry.
AB  - The stability of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde
      (NDA) was investigated using a combination of high-performance liquid
      chromatography, solid-phase extraction, photodiode array spectrophotometric
      detection, and mass spectrometric (MS) characterization. The degradation of amino
      acid derivatives, generated using beta-mercaptoethanol as a nucleophile, was
      characterized under a variety of environmental influences, with a focus on
      understanding the degradation kinetics and identifying the degradation products.
      The predominant degradation product observed under most reaction conditions was
      the nonfluorescent lactam form of the originally fluorescent isoindole
      derivative. First, the time-dependent degradation of the isoindole derivative L
      serine-NDA-beta-mercaptoethanol was found to follow pseudo-first order kinetics
      with a half-life of 2.0 min at pH 9.2 and room temperature. The isoindole
      derivative was observed to react further with methanol to form a more stable
      fluorescent methoxy-isoindole, shedding new light on the basis for enhanced
      stability of these derivatives in methanol. Tandem mass spectrometry (MS/MS)
      experiments were used to demonstrate unimolecular degradation of the protonated
      isoindole in the absence of solvent or atmosphere, suggesting an intramolecular
      reaction mechanism involving the hydroxyethylthio group. Finally, in
      photobleaching studies, NDA derivatives rapidly degraded into a variety of
      products within the first 2 min of photobleaching versus timed controls, with the
      predominant product being the lactam. These results suggest that the degradation
      pathway for NDA derivatives is similar to the previously reported pathway for o
      phthalaldehyde derivatives and clearly identifies the reaction and degradation
      products under a variety of conditions.

PMID- 14705783
TI  - Characterization of DNA adducts from lung tissue of asphalt fume-exposed mice by
      nanoflow liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - A bioanalytical method based on nanoflow liquid chromatography coupled to a
      hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometry was
      developed to characterize selected polyaromatic hydrocarbon (PAH)-DNA adducts.
      The collision-induced dissociation of analytes results in characteristic
      fragmentation patterns that can be utilized to identify the DNA adducts. In the
      experiment, 32 B6C3F1 mice were exposed daily (4h/day) to asphalt fume in a whole
      body inhalation chamber for 10 days; 16 nonexposed mice served as controls. The
      asphalt fume was generated at 180 degrees C and the concentrations of PAHs in the
      animal exposure chamber ranged from 152 to 198 mg/m3. The DNA adducts N2
      deoxyguanosine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N2-dG-BPDE); N6
      deoxyadenosine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N6-dA-BPDE), and N4
      deoxycytidine-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (N4-dC-BPDE) were
      identified. The concentrations of N2-dG-BPDE, N6-dA-BPDE, and N4-dC-BPDE adducts
      were determined to be 1.17, 0.97, and 0.68 pmol/mg DNA, respectively, in the lung
      tissue of exposed mice using the nanoflow technique. The total DNA adducts in
      exposed lung tissue was determined to be 8.35 pmol/mg DNA by 32P-postlabeling
      assay. In total, the results indicated that PAH DNA adducts were significantly
      elevated (p < 0.001) in the lung tissue of asphalt-fume-exposed mice relative to
      tissue from control animals.

PMID- 14705784
TI  - A mathematical model of lateral flow bioreactions applied to sandwich assays.
AB  - Lateral flow (LF) biodetectors facilitate low-cost, rapid identification of
      various analytes at the point of care. The LF cell consists of a porous membrane
      containing immobilized ligands at various locations. Through the action of
      capillary forces, samples and reporter particles are transported to the ligand
      sites. The LF membrane is then scanned or probed, and the concentration of
      reporter particles is measured. A mathematical model for sandwich assays is
      constructed and used to study the performance of the LF device under various
      operating conditions. The model provides insights into certain experimental
      observations including the reduction in the level of the detected signal at high
      target analyte concentrations. Furthermore, the model can be used to test rapidly
      and inexpensively various operating conditions, assist in the device's design,
      and optimize the performance of the LF device.

PMID- 14705785
TI  - Sulfonation of polyvinylidene difluoride resin and its application in extraction
      of restriction enzymes from DNA digestion solutions.
AB  - Sulfonation of polyvinylidene difluoride (PVDF) resin was achieved by incubation
      of the resin with sulfuric acid at a moderately high temperature. The sulfonated
      PVDF (SPVDF) resin was studied for its ability to extract restriction enzymes
      from DNA digestion solutions. The SPVDF resin was effective in adsorbing
      restriction enzymes such as EcoRI and BamHI and the extraction procedure was easy
      and simple to perform. The adsorption depended upon the amount of the resin
      added. We found that 1 mg of the SPVDF resin could completely remove all
      restriction enzyme activity routinely used in DNA digestion within 2 min after
      its addition. Treatment of a digestion solution with the SPVDF resin did not
      change the reaction solution and the same digestion buffer could be used for
      another digestion of the same DNA with other enzymes. We also found that, in
      comparison with normal PVDF, the SPVDF resin adsorbed less DNA, resulting in less
      loss of DNA in the extraction step. The potential application of the SPVDF resin
      in other procedures of molecular cloning and enzyme purification is discussed.

PMID- 14705786
TI  - Separation and quantification of chicken and bovine growth plate cartilage matrix
      vesicle lipids by high-performance liquid chromatography using evaporative light
      scattering detection.
AB  - Matrix vesicles (MV) are lipid bilayer-enclosed nanoscale structures that
      initiate extracellular mineral formation in most vertebrate species. Little
      attention has been given to differences between species in membrane lipid
      composition or to how new mineral is formed in MV. To explore more precisely the
      lipids of MV isolated from avian and bovine species, we developed a new high
      performance liquid chromatography (HPLC) method used in combination with
      evaporative light scattering detection (ELSD) to quantify their lipid
      composition. HPLC analyses were performed on a Lichrosorb silica column using
      separate binary gradient elution systems for analyzing polar and nonpolar lipids.
      Standard mixtures of both phospholipids and nonpolar lipids were used to prepare
      calibration curves for each lipid, which were analyzed mathematically by
      polynomial regression for accurate quantitation. This new methodology provides
      high-resolution separations and quantitation of both the polar and the nonpolar
      lipids typically present in biological membranes, including lyso- (monoacyl-)
      phospholipids. We have applied this method to quantitate the phospholipid and
      nonpolar lipid composition of MV isolated from chicken and bovine growth plate
      cartilage. We also compared the ability of these MV to induce mineral formation.
      While the ability to induce mineralization and the lipid composition were
      generally similar, some significant differences between MV from these two
      disparate species were seen.

PMID- 14705787
TI  - A continuous assay of myristoyl-CoA:protein N-myristoyltransferase for proteomic
      analysis.
AB  - Protein N-myristoylation is an important lipid modification that affects the
      activity and membrane-binding properties of crucial proteins belonging to signal
      transduction cascades. The aim of this work was to develop a rapid and easy
      diagnostic method to check for (i) effective N-myristoylation of any given
      protein and (ii) easy proteome annotation. The N-myristoylation reaction was
      coupled to that of pyruvate dehydrogenase, and NADH was continuously detected
      spectrophotometrically. This method was optimized for and applied to full-length
      Saccharomyces cerevisiae and Arabidopsis thaliana N-myristoyltransferases and two
      A. thaliana enzyme derivatives. The data were validated by comparison with a
      previously described discontinuous assay, modification of the chemical nature of
      the substrates, and use of specific inhibitors. The kinetics of N-myristoylation
      were determined in vitro with various compounds including a full-length
      polypeptide substrate, a small G protein of the RAB family already known to be N
      myristoylated in vivo. This automated assay can be used for proteomic studies to
      determine the N-myristoylation state of any protein.

PMID- 14705788
TI  - Hybridization-responsive fluorescent DNA probes containing the adenine analog 2
      aminopurine.

PMID- 14705789
TI  - Comparison of real-time polymerase chain reaction and hybridization assays for
      the detection of Escherichia coli genomic DNA in process samples and
      pharmaceutical-grade plasmid DNA products.

PMID- 14705790
TI  - Colorectal cancers with mononucleotide microsatellite instability can be
      identified using microfabricated chip technology.

PMID- 14705791
TI  - Simultaneous analysis of amino and nonamino organic acids as methyl chloroformate
      derivatives using gas chromatography-mass spectrometry.

PMID- 14705792
TI  - Molecular genetics of Xeroderma pigmentosum variant.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by sun
      sensitivity, early onset of freckling and subsequent neoplastic changes on sun
      exposed skin. Skin abnormalities result from an inability to repair UV-damaged
      DNA because of defects in the nucleotide excision repair (NER) machinery.
      Xeroderma pigmentosum is genetically heterogeneous and is classified into seven
      complementation groups (XPA-XPG) that correspond to genetic alterations in one of
      seven genes involved in NER. The variant type of XP (XPV), first described in
      1970 by Ernst G. Jung as 'pigmented xerodermoid', is caused by defects in the
      post replication repair machinery while NER is not impaired. Identification of
      the XPV gene was only achieved in 1999 by biochemical purification and sequencing
      of a protein from HeLa cell extracts complementing the PRR defect in XPV cells.
      The XPV protein, polymerase (pol)eta, represents a novel member of the Y family
      of bypass DNA polymerases that facilitate DNA translesion synthesis. The major
      function of (pol)eta is to allow DNA translesion synthesis of UV-induced TT
      dimers in an error-free manner; it also possesses the capability to bypass other
      DNA lesions in an error-prone manner. Xeroderma pigmentosum V is caused by
      molecular alterations in the POLH gene, located on chromosome 6p21.1-6p12.
      Affected individuals are homozygous or compound heterozygous for a spectrum of
      genetic lesions, including nonsense mutations, deletions or insertions,
      confirming the autosomal recessive nature of the condition. Identification of
      POLH as the XPV gene provides an important instrument for improving molecular
      diagnostics in XPV families.

PMID- 14705793
TI  - Carbohydrate expression and modification during keratinocyte differentiation in
      normal human and reconstructed epidermis.
AB  - Using fluorescein isothiocyanate (FITC)-labeled lectins we were able to
      demonstrate the presence of specific carbohydrate moieties in normal human and
      reconstructed epidermis. Evidence is provided that in both cases the strongly
      reduced lectin staining at the level of the stratum corneum is the result of a
      hindered accessibility of the lectins in this lipid-rich hydrophobic environment.
      Isolated corneocytes and purified cornified envelopes (CEs) exhibited clearly
      glycosylated structures reacting with distinct lectins. The presence of
      glycosidase activity, particularly in the upper layers of the epidermis
      characterized by an acidic environment (pH 5.5), indicates that modifications of
      the sugar residues might be important in epidermal homeostasis, barrier behavior
      and desquamation. Absent or strongly reduced glycosidase activity in the stratum
      corneum of reconstructed epidermis with an impaired pH gradient could be in part
      responsible for the reduced barrier function and the lack of desquamation in this
      model.

PMID- 14705794
TI  - Internalization via plasmalemmal vesicles: a route for antidesmoplakin
      autoantibodies into cultured human keratinocytes.
AB  - Recently, autoantibodies to desmoplakin I and II have been identified in a subset
      of patients with a severe form of erythema multiforme. These autoantibodies
      recognize a specific peptide sequence at the carboxy terminal domain of
      desmoplakin I and II responsible for interaction with keratin filaments.
      Desmoplakins are major constitutive proteins of the inner dense desmosomal plaque
      of keratinocytes and are entirely localized within the cells. With the assumption
      of pathogenecity for circulating autoantibodies, the question arose how
      antidesmoplakin autoantibodies enter keratinocytes. Utilizing immunhistochemical
      procedures for cell motility and time kinetic studies at the light- and electron
      microscopic level, we found that autoantibodies are bound at the cell surface of
      cultured human keratinocytes, internalized via plasmalemmal vesicles, and are
      found consecutively within tubulovesicular structures inside the cells. At the
      same time, a fraction of antibodies can be detected at the inner dense desmosomal
      plaques. Immunogold labeling reveals internalization of autoantibodies in small
      non-coated plasmalemmal vesicles positive for caveolin. These observations
      indicate that vesicular transport may represent a relevant biological mechanism
      for antidesmoplakin autoantibodies to enter keratinocytes and allow access to
      their corresponding antigenic target in vivo.

PMID- 14705795
TI  - Naive CD4+ T cells from patients with atopic dermatitis show an aberrant
      maturation towards IL-4-producing skin-homing CLA+ cells.
AB  - Overproduction of interleukin-4 (IL-4) has been reported in lesional and in
      peripheral T cells from patients with atopic dermatitis (AD). It is not clear
      whether the development of IL-4-producing T helper type 2 (Th2) cells from naive
      precursors is an intrinsic phenomenon of T cells or whether other, extrinsic
      factors play a significant role. To analyze these alternatives, we investigated
      the IL-4 production of effector T cells generated in vitro from highly purified
      CD4+ CD45RA+ naive T cells in the absence of signals derived from antigen
      presenting cells. Effector T cells generated from naive precursors from both AD
      and healthy donors produced comparable amounts of IL-4 after restimulation.
      Priming in the presence of exogenous IL-4 enhanced the production of IL-4 while
      neutralizing endogenously produced IL-4 abolished IL-4 production similarly in
      atopic and healthy T cells. A subset of effector T cells acquired the expression
      of the cutaneous lymphocyte antigen (CLA). The frequency of CLA+ T cells was not
      different between atopic and healthy donors. CLA+ T cells, differentiated from
      naive atopic, but not healthy T cells, showed a preferential Th2 cytokine profile
      as assessed by intracellular cytokine staining. Also effector T cells derived
      from atopic patients without dermatitis tended to show this imbalance, although
      it was not significantly different to healthy controls. This Th2 cytokine profile
      did not develop when naive T cells were cultured in the presence of IL-12. In
      conclusion, high IL-4 production in developing T cells from AD patients was
      associated with CLA expression, the net IL-4 production of all effector CD4+ T
      cells, however, was similar to IL-4 production by T cells from healthy donors.

PMID- 14705796
TI  - Differential effects of UV irradiation on nuclear retinoid receptor levels in
      cultured keratinocytes and melanocytes.
AB  - A major risk factor for skin cancer is UV irradiation, which not only damages DNA
      and other photosensitive compounds like vitamin A, but may also perturb cellular
      signaling, e.g. via the retinoid receptor system believed to be important for
      cancer protection. We used cultured normal human keratinocytes and melanocytes to
      examine the effects of UV irradiation on the expression of the predominant
      retinoid receptors in the human skin (RARalpha, RARgamma and RXRalpha) and the AP
      1 protein c-Jun; mRNA levels were studied by real-time PCR and protein levels by
      Western blot. In keratinocytes, a single dose of UVB (50 mJ/cm2) caused a rapid
      drop in the expression of all three receptors (mRNA levels minus 35-50% after 4
      h; protein levels minus 20-45% after 8 h), which was followed over the next 40 h
      by a variable response, leading to full normalization for RARalpha only. In
      contrast, the levels of c-Jun did not change significantly after UV exposure. In
      melanocytes, UVB caused a similar drop of the retinoid receptor levels as in
      keratinocytes but this was soon followed by an increased expression leading to a
      complete normalization of all receptor levels within 1-3 days. The c-Jun levels
      in melanocytes increased 1 day after UV exposure and remained high (plus 50%)
      thereafter. In both cell types, a approximately 3-fold increase in apoptosis
      (measured by DNA fragmentation) was observed 8-48 h after UVB irradiation. In
      conclusion, a depletion of vitamin A and retinoid receptors by UV irradiation,
      together with unchanged or even increased c-Jun levels, might seriously interfere
      with retinoid signaling and thus promote future tumor development, especially in
      keratinocytes.

PMID- 14705797
TI  - Human epidermal energy metabolism is functionally anaerobic.
AB  - We have reported that epidermal Langerhans cells possess an H(+)-extruding
      mechanism signalling their existence in an anaerobic environment. This study
      highlights the energy metabolism of human epidermis. In their habitual state the
      keratinocytes contain more lactate than do most other cell types. Their lactate
      production in vitro is vigorous and independent of oxygen and most of it is
      released to the medium. Autoincubation of the epidermis under starved conditions
      resulted in a 30% increase of lactate, indicating ongoing glycogenolysis.
      Iodoacetate inhibited lactate production by > 90%. Energy charge values were low,
      approximately 0.82, and comparable with those previously reported for smooth
      muscle. Moreover, the overwhelming majority of the keratinocytic mitochondria had
      an appearance markedly deviating from those in the Langerhans cells, melanocytes
      and fibroblasts, and, above all, were characterized by an enormous reduction of
      the inner membrane. This structure is in all probability incompatible with an
      effective oxidative metabolism of glucose. We conclude that epidermal energy
      metabolism is predominantly anaerobic in spite of the formal presence of
      mitochondria. The high production of lactate obviously demands extracellular
      transport pathways for rapid elimination of this organic acid. An extracellular
      space complying with such a demand emerges on electron microscopy when an
      isotonic glutaraldehyde-based fixative is used. The prevailing view regarding the
      size of the extracellular space is based on the common use of hypotonic
      fixatives, such as Karnovski's fixative, which causes gross cellular swelling and
      concomitant near total elimination of the extracellular space, leaving
      interstices with a diameter significantly smaller than that allowing fluid flow.

PMID- 14705798
TI  - Topical minoxidil counteracts stress-induced hair growth inhibition in mice.
AB  - Stress has long been suspected as a possible cause of hair loss in various
      species, even though convincing experimental evidence has not been available.
      Recently, we have shown in a murine model that sonic stress alters hair growth
      and cycling in vivo, and have postulated the existence of a 'brain-hair follicle
      axis' (BHA). In order to study whether a clinically available and widely used
      topically active hair growth stimulator mitigates stress-triggered hair growth
      inhibition in this stress model, we have applied a 5% minoxidil solution. Female
      CBA/J mice were depilated and randomized in to two groups: control (n = 20) and
      sonic stress (n = 20). These groups were further divided and either treated daily
      with 5% minoxidil solution or vehicle alone. The stress group was exposed to
      sonic stress for 24 h starting 14 days after anagen induction by depilation. All
      mice were sacrificed 16 days after the depilation and assessed by quantitative
      histomorphometry. Sonic stress significantly increased the number of hair
      follicles with apoptotic cells and inhibited intrafollicular keratinocyte
      proliferation. In addition, the number of clusters of perifollicular MHC class
      II+ cells and degranulated perifollicular mast cells was significantly enhanced
      in the stressed mice. In accordance with previous findings, all stressed mice
      showed an advanced hair cycle progression towards catagen. All of these stress
      induced hair growth inhibitory changes along the BHA were down-regulated by
      topical minoxidil application. This encourages one to explore clinically whether
      topical minoxidil is a safe and effective pharmacologic tool for the management
      of stress-associated telogen effluvium in humans.

PMID- 14705799
TI  - Ratio of immature cornified envelopes does not correlate with parakeratosis in
      inflammatory skin disorders.
AB  - We have previously established a non-invasive method to evaluate the maturity of
      cornified envelopes (CEs), and have reported the appearance of immature CEs in
      the stratum corneum (SC) with poor barrier function, such as the SC of the face.
      The purpose of the present study was to evaluate CEs in inflammatory skin
      disorders, and to clarify the relationship between the appearance of the immature
      CEs and parakeratosis, which is often used as a marker for defective
      keratinization in inflammatory skin disorders. Cornified envelopes in the
      outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis
      (AD) were strikingly heterogeneous, and consisted of immature CEs stained with
      anti-involucrin and mature CEs stained with Nile red, whereas CEs of the
      uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The
      ratio of immature CEs was significantly higher in the involved areas of PV and AD
      than that in the corresponding uninvolved areas, suggesting that defective CE
      maturation may, at least in part, account for the inflammatory disorders.
      Simultaneous evaluation of CE maturity and parakeratosis was carried out by a
      combination of involucrin immunostaining and nuclear staining of detergent
      dissociated corneocytes. In the involved area of PV, four types of corneocytes in
      regard to the combination of involucrin staining and nuclear remnant were
      observed, while both immature CEs and parakeratosis were more often detected in
      the involved areas of PV than in the uninvolved areas or the upper arm of healthy
      subjects as a normal control. Thus, corneocytes with involucrin-positive immature
      CEs were not always associated with parakeratosis at the cellular level. In the
      involved areas of PV, the ratio of immature CEs and that of parakeratosis were
      heterogeneous, depending on the cases, and no correlation between the ratios was
      observed. Inter-individual and intraindividual variations in CE maturity were
      also suggested by the heterogeneous localization of involucrin in the psoriatic
      epidermis as examined by immunohistochemistry. In addition, in the face of
      healthy subjects, four types of corneocytes were similarly detected, and the
      ratio of immature CEs was significantly higher than that of parakeratosis. These
      results obviously suggest that the maturation of CEs and disappearance of nuclei
      are differentially regulated in the epidermis.

PMID- 14705800
TI  - New mechanism for amino acid influx into human epidermal Langerhans cells: L
      dopa/proton counter-transport system.
AB  - We have characterized a stereospecific transport mechanism for L-dopa into human
      epidermal Langerhans cells (LCs). It is different from any other amino acid
      transport system. It is highly concentrative, largely pH-independent, and
      independent of exogenous Na+, glucose and oxygen, and fuelled by a renewable
      intracellular energy source inhibited by iodoacetate but not by arsenate. We
      propose that the mechanism is a unidirectional L-dopa/proton counter-transport
      system. We have recently demonstrated anaerobic glycolysis in human epidermis,
      which substantiates the need of proton pumps for resident LCs. The findings
      prompt a re-evaluation of the profound changes LCs undergo when exposed to oxygen
      in aerobic culture. L-dopa is not metabolized by LCs but can rapidly be
      dislocated to the intercellular space by certain extracellular amino acids, i.e.
      LCs can profit by L-dopa in a dualistic way, altogether a remarkable biological
      phenomenon.

PMID- 14705801
TI  - High-dose long wave visible light induces perinuclear vacuolization in vivo but
      does not result in early photoageing and apoptosis.
AB  - With the advancing widespread use of photodynamic therapy, questions have arisen
      about the necessity to protect the adjacent healthy skin from high-dose long-wave
      light. The aim of the present study was to investigate the effects of high dose
      visible light on the skin of healthy volunteers with focus on apoptosis, DNA
      damage, inflammation, melanogenesis and induction of matrix metalloproteinases
      (MMP). Fourteen healthy volunteers were included and irradiated daily on their
      buttocks with 1300 kJ/m2 long wave visible light (560-780 nm) on five consecutive
      days with a cumulative dose of 6500 kJ/m2. In each volunteer six biopsies were
      taken before and 24 h after irradiation on days 1, 2, 3 and 5 and on day 8 and
      12. Frozen and paraffin sections were investigated by measuring parameters for
      photodamage (apoptosis, p53, phosphorylated c-Jun), skin ageing (phosphorylated c
      Jun, MMP-1, elastin content) melanogenesis (Melan A). Although no sunburn cells
      were seen, a significant increase in perinuclear vacuolization was noted (P <
      0.0003) from day 5 till 7 days after the last irradiation. There was no
      expression of phosphorylated c-Jun, whereas the expression of p53, Melan A, MMP-1
      and elastin content did not change. High-dose visible light induces a significant
      increase in perinuclear vacuolization, but does not result in apoptosis,
      photodamage or early induction of skin ageing.

PMID- 14705802
TI  - Effect of the lactic acid bacterium Streptococcus thermophilus on stratum corneum
      ceramide levels and signs and symptoms of atopic dermatitis patients.
AB  - A reduced amount of total ceramides could be responsible for functional
      abnormalities of the skin of atopic dermatitis (AD) patients. The ability of an
      experimental cream containing sonicated Streptococcus thermophilus to increase
      skin ceramide levels in healthy subjects has been previously reported. The aim of
      the present work was to investigate the effects of the topical administration of
      a S. thermophilus-containing cream on ceramide levels of stratum corneum from AD
      patients. A 2-week application of the cream, containing a sonicated preparation
      of the lactic acid bacterium S. thermophilus, in the forearm skin of 11 patients
      led to a significant and relevant increase of skin ceramide amounts, which could
      have resulted from the sphingomyelin hydrolysis through the bacterial
      sphingomyelinase. Moreover, in all patients the topical application of our
      experimental cream also resulted in the improvement of the signs and symptoms
      characteristic of AD skin (i.e. erythema, scaling, pruritus).

PMID- 14705803
TI  - Infiltrating cells and related cytokines in lesional skin of patients with
      chronic idiopathic urticaria and positive autologous serum skin test.
AB  - In approximately one-third of patients with chronic idiopathic urticaria (CIU),
      autoantibodies against the high-affinity IgE receptor and/ or against IgE can be
      detected and a wheal-and-flare response can be provoked by the intradermal
      injection of autologous serum (ASST). In this study we aimed to further
      characterize the inflammatory response observed in the subgroup of CIU patients
      with positive ASST and serum-evoked histamine-release in vitro from basophils in
      comparison with unaffected skin and healthy donors. An immunohistochemical
      analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4,
      IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and
      adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected
      patients (four males and three females; median age: 45 years; range: 22-57) and
      five healthy donors. Cytokine evaluation was also performed in five psoriatic
      patients to obtain an additional control. In spontaneous wheals we observed an
      increased number of CD4+ T lymphocytes when compared with the controls, and an
      increased number of neutrophils and eosinophils, whereas mast cells did not show
      a significant variation. A significant expression for IL-4 and IL-5 could only be
      observed in lesional skin, while IFN-gamma showed a slight expression in the same
      site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized
      response in either lesional or unaffected skin. An increased expression of all
      cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals.
      The lack of a significant difference in the expression of tryptase + mast cells,
      T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and
      unaffected skin of CIU patients suggests a wide immunological activation that
      involves not only lesional tissues, but possibly extends to the whole of the
      skin's immune system.

PMID- 14705804
TI  - Long-term growth arrest of PUVA-treated fibroblasts in G2/M in the absence of
      p16(INK4a) p21(CIP1) or p53.
AB  - Premature aging of the skin is a prominent side-effect of psoralen
      photoactivation, a therapy used for different skin disorders. Recently, we
      demonstrated that treatment of fibroblasts with 8-methoxypsoralen and ultraviolet
      A irradiation resulted in growth arrest with morphological and functional changes
      reminiscent of replicative senescence. To further elucidate the underlying
      molecular mechanisms, we analysed the cell-cycle phases of the growth-arrested
      fibroblasts. After PUVA treatment, fibroblasts arrested in G2/M, in contrast to
      spontaneously senesced fibroblasts arresting in a cell-cycle phase with many
      features similar to G1. To address the role of the cell-cycle controlling genes
      p16(INK4a), p21(CIP1) and p53, we analysed the expression of these genes.
      p16(INK4a), p21(CIP1) and p53 protein levels increased substantially with
      different time kinetics in growth-arrested fibroblasts. Because p16(INK4a),
      p21(CIP1) and p53 are involved in replicative senescence, we applied the PUVA
      regimen to fibroblasts deficient in either of these genes. p16(INK4a), p21(CIP1)
      and p53 null mutant fibroblast strains underwent growth arrest with a senescent
      phenotype similar to wild-type human fibroblasts. Based on these results, we
      propose that redundant or alternate pathways are involved in the response of
      dermal fibroblasts to PUVA treatment resulting in a phenocopy of replicative
      senescence in vitro.

PMID- 14705805
TI  - Disruption of the suprabasal keratin network by mutation M150T in the helix
      initiation motif of keratin 10 does not affect cornified cell envelope formation
      in human epidermis.
AB  - Keratin 10 (K10) is known to be tightly bound to the cornified cell envelope
      (CCE) and this binding is thought to play an important role in enhancing the
      structural integrity of the cornified cells. Bullous congenital ichthyosiform
      erythroderma (BCIE) is a genetic disorder of keratinization caused by gene
      mutations in the conserved sequences of keratin 1 (K1) or K10, which leads to
      abnormal suprabasal keratin network assembly. In BCIE patients' skin, the keratin
      network abnormalities make the upper spinous and granular keratinocytes fragile
      and result in blister formation. However, the exact pathomechanism of the
      hyperkeratosis seen in BCIE is still unknown. The involvement of the CCE in the
      pathomechanism of hyperkeratosis in BCIE is controversial. Abnormal CCE assembly
      may cause hyperkeratosis as reported in cases of lamellar ichthyosis. Binding of
      K10 to CCE is thought to be a vital connection between the suprabasal keratin
      filament network and CCE. We hypothesize that abnormal suprabasal keratin
      assembly caused by either K1 or K10 mutations can disrupt CCE formation,
      resulting in the hyperkeratosis observed in BCIE. To clarify whether K10 and
      keratin network defects affect CCE formation in vivo, the ultrastructural and
      immunohistological features of CCE were studied in the epidermis of two Japanese
      BCIE patients from two independent families carrying an identical missense
      mutation M150T in the helix initiation motif of K10. Ultrastructurally, a 15-nm
      thick, dense, normal-appearing CCE was formed at the cell periphery of the
      keratinized epidermal cells. Light and electron microscopic immunolabeling
      revealed that the major CCE precursor proteins, involucrin and loricrin, were
      normally distributed and restricted to CCE of the epidermis. Immunofluorescent
      labeling showed that epidermal TGases, TGase 1, TGase 2 and TGase 3, were
      expressed normally in the epidermis. These findings suggest that a normal CCE is
      formed during the process of human epidermal keratinization, even if the
      suprabasal keratin filament network is disrupted as with this particular K10
      mutation, M150T in BCIE.

PMID- 14705806
TI  - 230-kDa and 190-kDa proteins in addition to desmoglein 1 as immunological targets
      in a subset of pemphigus foliaceus with a combined cell-surface and basement
      membrane zone immune staining pattern.
AB  - Pemphigus erythematosus, initially described as a combination of pemphigus with
      lupus erythematosus, and pemphigus foliaceus are now frequently considered
      localized and generalized variants of superficial pemphigus. Yet diagnostic
      criteria for pemphigus erythematosus remain controversial. Distinct from
      pemphigus foliaceus, pemphigus erythematosus displays immune depositions at the
      dermal-epidermal junction, which suggests additional immunopathological
      mechanisms. We present three patients with clinical and histopathologic signs of
      superficial pemphigus, who all exhibited an immunomorphology characteristic of
      pemphigus erythematosus. Complement depositions in a granular-linear fashion were
      consistently found at the dermal-epidermal junction besides in vivo bound and
      circulating antikeratinocyte cell-surface autoantibodies. Histopathology showed
      subcorneal acantholysis, and all sera contained antidesmoglein 1 but not
      antidesmoglein 3 autoantibodies detected by enzyme-linked immunosorbent assays
      (ELISA). Additional autoantibodies against a 230-kDa protein and against a 190
      kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin,
      respectively, were present in all the patients' sera. As two sera specifically
      reacted with BP230 by ELISA, the presence of BP230-specific autoantibodies could
      be associated with dermal-epidermal immune staining in these patients. In
      pemphigus erythematosus, dermal-epidermal immune staining is generally attributed
      to the deposition of immune complexes, while the presence of BP230-specific
      autoantibodies has not been reported in this disease previously. Perhaps, the
      unique autoantibody profile of the patients in the study permits discrimination
      between patients with superficial pemphigus that display additional dermal
      epidermal immune staining from those with conventional pemphigus foliaceus on a
      molecular basis. Further studies will be required to substantiate the frequency
      of this occurrence and to unravel its pathogenic significance.

PMID- 14705807
TI  - Age-dependent generation of reactive oxygen species in the skin of live hairless
      rats exposed to UVA light.
AB  - Aging proceeds by highly complicated biochemical processes, in which the
      involvement of the reactive oxygen species (ROS) and free radicals has been
      implicated. Although the relationship between UV-induced photoaging and ROS
      generation has been proposed, it has been difficult to establish direct proof of
      the generation of ROS in the skin under UV exposure. Recently, we reported
      finding endogenously generated ROS in the skin of live mice after UVA light
      exposure by a method of in vivo chemiluminescent detection, in which superoxide
      anion radical (*O2-) and singlet oxygen species (1O2) are contributed. In light
      of the results, we tried to understand the age-dependent changes in ROS
      generation in the skin of hairless rats under UVA exposure. Chemiluminescent
      levels due to ROS in the untreated and UVA-exposed skin decreased age
      dependently, and the signal intensities in old rats were significantly lower than
      those in young rats. However, the ratios of chemiluminescent intensities in the
      UVA-exposed skin to those in the untreated skin were significantly enhanced in an
      age-dependent manner. These results suggest that the antioxidative ability
      against ROS generation in the skin, possessed by antioxidant enzymes and low
      molecular weight antioxidants, is lowered age dependently.

PMID- 14705808
TI  - Regulation of PDGF and PDGF receptor in cultured dermal papilla cells and
      follicular keratinocytes of the human hair follicle.
AB  - Platelet-derived growth factor (PDGF) is a potent mitogenic factor for many cell
      types and has been shown to be important in follicular development and
      vasculogenesis. In this study, we examined the expression pattern of both PDGF
      factors and their corresponding receptors in mesenchyme-derived dermal papilla
      cells (DPCs) and epithelial follicular keratinocytes (FKs). Both types of PDGF
      receptors are expressed in FKs, whereas DPCs only express PDGF receptor beta on
      the protein level, a finding also seen in whole organ cultures. By examining the
      expression of PDGF ligands, we were able to show that cultured FKs synthesize
      both PDGF-A and PDGF-B, whereas, DPCs only express PDGF-A. As immunomodulatory
      cytokines were shown to affect hair growth, we investigated the effects of IL
      1beta, IL-4, TNF-alpha, TGF-beta and IFN-gamma on the expression levels of PDGF
      factors in cultured DPCs and FKs. Interestingly, we could show a significant down
      regulatory effect by catagen-inducing cytokines like IL-1beta or IFN-gamma,
      suggesting a possible involvement of PDGF signaling in the induction of catagen.
      The question concerning the latter hypothesis remains to be elucidated in further
      studies on whole organ cultures.

PMID- 14705809
TI  - Cryotherapy modifies synthetic activity and differentiation of keloidal
      fibroblasts in vitro.
AB  - In order to obtain a persuasive explanation for the beneficial clinical effect of
      cryotherapy on keloids, we developed a reproducible model to apply freezing
      temperatures on cell cultures, and investigated their influence on proliferation,
      viability, synthetic activity and differentiation of dermal fibroblasts in vitro.
      Cell cultures were established from 13 untreated keloids and 10 healthy skin
      specimens matched for age and skin localization to the donors. No significant
      influence of cell freezing on the proliferation rates of both keloidal and normal
      fibroblasts was documented, but mechanical cell destruction with a wide variation
      in lethality rates (29% average lethal effect on keloidal fibroblasts and 41% on
      normal ones) was observed. When comparing specimens of keloidal and normal tissue
      derived from the same four donors, the keloidal fibroblasts were similar
      regarding their synthetic activity but presented enhanced tenascin-C expression
      compared with the normal fibroblasts. After cryotherapy, delayed collagen III
      increase was detected in both cell types (P = 0.03). The collagen II/collagen I
      ratio increased from 1.6 to 2.8 in the keloidal and only from 1.9 to 2.2 in the
      normal fibroblasts after subcultivation. Normal fibroblasts exhibited a
      significantly lasting increase in fibronectin synthesis after freezing (P =
      0.03). The intensity of staining against tenascin-C was decreased in five of nine
      keloidal fibroblast cultures after cryotherapy (P < 0.05) but increased in four
      of five normal fibroblast cultures (P = 0.016), so that the intensity of tenascin
      C staining after freezing became identical in both cell types. Immunoblot studies
      in four patients and two controls confirmed a temporary decrease of tenascin-C in
      keloidal but not in normal fibroblasts immediately after freezing. Significantly
      decreased staining with two markers of myogenic differentiation, myosin in
      keloidal fibroblasts (P = 0.002) and desmin (P = 0.007) in normal fibroblasts,
      could also be detected after treatment. In summary, with the help of a model for
      controlled cell freezing in vitro, cryotherapy was found to modify collagen
      synthesis and differentiation of keloidal fibroblasts.

PMID- 14705810
TI  - Comparison of two in vitro dendritic cell maturation models for screening contact
      sensitizers using a panel of methacrylates.
AB  - Allergen-induced emigration and maturation of dendritic cells (DC) are pivotal
      steps in sparking off allergic contact dermatitis. In vitro models, reflecting
      these steps, may provide tools for assessment of sensitizing capacities of
      putative contact allergens. Here, we evaluated the applicability of such models
      for a panel of methacrylate congeners, the sensitizing properties of which were
      established previously in clinical and experimental animal studies. First, using
      interleukin-4 (IL-4)/granulocyte-macrophage colony-stimulating factor (GM-CSF)
      induced, blood monocyte-derived DC, hapten-induced up-regulation of maturation/
      activation markers, including CD80, CD83, CD86, chemokine receptors CXCR4 and
      CCR5, as well as the drug resistance related molecules P-glycoprotein (Pgp) and
      lung resistance protein (LRP), were monitored by flow cytometry. Of note, whereas
      CD86 and CXCR4 were most sensitive in discriminating between the contact
      sensitizers and irritants included in the panel, i.e. sodium dodecyl sulphate
      (SDS) and croton oil (CO), assessment of CD83 and LRP expression reflected the
      relatively lower sensitizing capacity of methyl methacrylate. Second, using ex
      vivo skin explant cultures, allergen-induced LC migration from epidermal to basal
      membranous and dermal skin structures was most reliably monitored by CDla, as
      compared with Pgp, LRP, HLA-DR or CD54 staining. The extent of CD1a+ LC migration
      was found to closely correlate with the sensitizing capacities of the panel of
      test compounds. These results support the view that both in vitro models can
      provide valuable data on contact sensitizing properties, and add chemokine
      receptors and drug resistance related molecules to the list of DC membrane
      markers revealing allergenic signaling.

PMID- 14705811
TI  - The tolerogenic molecule CD95-L is expressed on the plasma membrane of human
      activated, but not resting, Langerhans' cells.
AB  - Although dendritic cells (DC) are well known for their immunogenic capacities,
      they may even induce peripheral T-cell tolerance, and such a tolerogenic
      potential can be exerted in mouse through the expression on the DC plasma
      membrane of the CD95-ligand (CD95-L) molecule, which is able to trigger apoptosis
      of CD95-expressing antigen-specific T cells. We therefore asked whether epidermal
      DC, namely Langerhans' cells (LC), either resting (i.e. within the epidermis, 'in
      situ') or activated (i.e. suspended from the epidermis) or both, could express
      the CD95-L molecule on the plasma membrane. For such a purpose, two colloidal
      gold-immunoelectron microscopy (IEM) double-step procedures were carried out: an
      'in situ' method, able to investigate resting LC, was performed on ultrathin
      frozen sections obtained by ultracryomicrotomy (UCMT) of normal skin biopsies; a
      pre-embedding (P-E) method, able to investigate suspended LC, was performed on
      epidermal cells (EC) suspended from normal skin specimens. In UCMT/IEM sections,
      resting LC showed gold particles within the cytoplasm but very rarely within
      organelles and never along the plasma membrane: resting LC are therefore capable
      of synthesizing CD95-L but not of expressing it in a functional location, thus
      autoreactive phenomena against CD95-expressing EC being avoided in normal
      epidermis. On the other hand, in P-E/IEM preparations, suspended LC showed
      several gold particles along the plasma membrane: activated LC are therefore
      capable of expressing CD95-L in a functional location, thus bearing the potential
      to exert tolerogenic capabilities against CD95-expressing T cells, e.g. to
      prevent inflammatory/autoimmune cutaneous disorders and/or favor the resolution
      thereof.

PMID- 14705812
TI  - CD4 is expressed by epidermal Langerhans' cells predominantly as covalent dimers.
AB  - Langerhans' cells (LC) of skin are CD4 expressing, dendritic, antigen-presenting
      cells, that are essential for activation of primary immune responses and are
      productively infected by HIV. We have shown previously that lymphocytes and
      monocytes express CD4 both as monomers and covalently linked homodimers. In those
      cells the 55-kDa monomer structure predominates. LC in un-fractionated human
      epidermal cell (EC) suspension also expresses both forms of CD4, but in EC the
      dimer form is predominant. Because isolation of LC into single cell suspension by
      trypsin, as is routinely used for LC isolation, degrades CD4, a systematic study
      for an alternate procedure for LC isolation was performed. Thus it was found that
      collagenase blend F treatment can efficiently release LC into suspension, under
      conditions of only minimal degradation of control soluble recombinant CD4 or CEM
      T4 or THP-1 cell CD4, or importantly of LC surface CD4. SDS-PAGE immunoblotting
      of purified LC extracted from EC by collagenase confirmed CD4 structure as
      predominantly 110-kDa dimers, with only minimal 55-kDa monomers. The suitability
      of LC prepared thus for functional studies was demonstrated with binding of
      functional ligand HIV gp120. It remains to be determined, however, why tissue
      embedded LC express mainly CD4 dimers, but single-celled blood lymphocytes and
      monocytes mainly monomers.

PMID- 14705813
TI  - Strategy to assess the efficiency of U1 RNA-hammerhead ribozyme constructs using
      GFP-tagged targets.
AB  - The application of ribozymes for gene therapy of autosomal dominant diseases has
      become popularized in recent years. Further this technology has widespread
      utility in the treatment of any disease, acquired or inherited, by inhibition of
      gene expression. The design of ribozymes is usually accomplished using computer
      assisted design programs, however they are not very useful in predicting the
      behavior of the ribozyme in the in vivo setting. To overcome this technical
      challenge, we developed a simple in vivo strategy to accurately assess the
      efficiency of ribozyme cleavage that significantly enhances the computer based
      design programs.

PMID- 14705814
TI  - Novel and recurrent mutations in the integrin beta 4 subunit gene causing lethal
      junctional epidermolysis bullosa with pyloric atresia.
AB  - In this study we examined two unrelated patients affected with the lethal variant
      of junctional epidermolysis bullosa with pyloric atresia (PA-JEB) who were found
      to carry mutations in the integrin beta4 subunit gene (ITGB4). Although in both
      patients Northern blot analysis showed only a 50% reduction in the level of ITGB4
      transcript, a complete lack (patient 1) or a strong reduction (patient 2) of
      beta4 immunoreactivity was observed in the skin. Using immunoprecipitation
      analysis, integrin beta4 could not be visualized in patient 1 cells while a
      markedly reduced amount (approximately 20%) of normal sized beta4 chains was
      detected in patient 2. These data suggested the presence of ITGB4 mutations that
      interfere with both mRNA and protein stability. Using molecular analysis, patient
      1 was shown to be a compound heterozygous for a single amino acid deletion
      (deltaN318) and a not yet identified mutation that induces a very rapid decay of
      the encoded mRNA transcript. Patient 2 was, instead, a compound heterozygous for
      a novel 4-bp tandem duplication (4298-4299ins4) and a previously described
      missense mutation (R252C). Our data support the notion that PA-JEB lethal
      phenotypes associated with a markedly decreased/absent alpha6beta4 expression can
      be due not only to the presence of null alleles, but also to specific mutations
      leading to protein instability and/or altered function.

PMID- 14705815
TI  - Manifestations of gastroesophageal reflux and response to omeprazole therapy in
      patients with chronic posterior laryngitis: an evaluation based on clinical
      practice.
AB  - Our aims were to describe clinical characteristics of patients with chronic
      posterior laryngitis and to predict the response to omeprazole therapy. Ninety
      one patients with posterior laryngitis were evaluated by a questionnaire,
      esophageal manometry and pH recording, and endoscopy. Patients were treated with
      omeprazole, 20 mg twice daily for 3 months. Therapy was continued another 3
      months if necessary. Clinical manifestations of reflux occurred in 84 (92%)
      patients, abnormal acid reflux in 53 (65%) cases, and esophagitis in 6 of 50
      (12%). After 3 months of therapy significant improvement occurred in 30 of 70
      patients (41%). Continuing therapy for 3 more months increased the response to
      65% (45 of 69 cases). Response to therapy was associated with lower age and lower
      duration of laryngeal symptoms, but a consistent prediction of the response could
      not be made. In conclusion, patients with posterior laryngitis frequently present
      with manifestations of gastroesophageal reflux. Response to therapy can not be
      predicted with certainty.

PMID- 14705816
TI  - Comparison of the esophageal manometric characteristics of idiopathic and reflux
      associated esophageal spasm: evaluation by 24-hour ambulatory esophageal motility
      and pH monitoring.
AB  - Diffuse esophageal spasm (DES) is a typical esophageal dysfunction, but its cause
      is unknown. DES has been classified into reflux-associated esophageal spasm
      (RDES), caused by acid exposure, and idiopathic esophageal spasm (IDES), of
      unknown causes. The differences in esophageal motility pattern between the RDES
      and IDES are clues to elucidating the pathogenesis of DES. Although 24-hr
      ambulatory esophageal motility and pH monitoring is considered a feasible method
      for evaluating gastroesophageal reflux and esophageal function, most researchers
      previously defined the RDES as DES accompanied by esophagitis and heartburn using
      standard manometry over a short time frame. To clarify the pathogenesis of RDES,
      we did this research using 24-hr ambulatory esophageal motility and pH
      monitoring. The investigation included 25 normal controls and 116 patients with
      upper digestive symptoms. Among the 116 patients, 45 had DES (11 RDES, 30 IDES,
      and DES-GERD coexistence). Patients with RDES showed a significantly higher
      frequency of simultaneous contractions than did patients with IDES. Heartburn has
      been said to be peculiar to RDES, but also occurred in 12.5% of IDES. No
      significant differences in the mean pH of the esophagus during acid reflux were
      found between the RDES and IDES patients. Based on the results, we have proposed
      a refined definition of RDES.

PMID- 14705817
TI  - Symptomatic lower esophageal muscular ring: response to botox.

PMID- 14705818
TI  - Utility of [13C] urea breath test for Helicobacter pylori detection in partial
      gastrectomy patients.
AB  - Many reports on the diagnostic efficacy of the [13C] urea breath test ([13C] UBT)
      for the detection of Helicobacter pylori in the residual stomach have shown
      negative results. We previously reported on the utility of [13C] UBT and
      conducted an evaluation to establish a standardized protocol with a shorter
      sampling time for [13C] UBT in partial gastrectomy patients. Sixty-two patients
      who had undergone partial gastrectomy were included. The [13C] UBT protocol
      included ingestion of 100 mg [13C] urea, use of mouthwash, and the body in a
      horizontal position on the left side. The sensitivity of [13C] UBT was 95.7%.
      Thirty minutes and a cutoff of 2.0 per thousand were found to be optimal for the
      test, with the body position horizontal on the left side. In the present protocol
      [13C] UBT appears to be a reliable and convenient tool with the same accuracy
      rate as other routine tests in patients with a remnant stomach.

PMID- 14705820
TI  - Esophagitis impairs esophageal smooth muscle reactivity in the rat model: an in
      vitro study.
AB  - The present study investigated how reflux-induced esophagitis affects the smooth
      muscle reactivity of the esophageal body. Two different esophagitis models were
      used: acid gastric and mixed duodenogastric reflux. All test animals apart from
      the controls developed gross and histologic evidence of esophagitis. Contractile
      (carbachol and KCI) and relaxant (isoproterenol) esophageal smooth muscle
      responses were significantly decreased in the presence of acid- and mixed reflux
      induced esophagitis. Similar relaxant responses to serotonin and papaverine were
      found in the three groups. Our study demonstrated impaired esophageal smooth
      muscle reactivity when esophagitis was induced by acid or mixed reflux. These
      changes may correspond to the functional motor abnormalities of the esophagus
      seen in patients with reflux esophagitis.

PMID- 14705819
TI  - Cyclooxygenase expression during Helicobacter pylori infection in Mongolian
      gerbils.
AB  - We investigated the expression of cyclooxygenase-2 (COX-2) and COX-1 mRNAs during
      longterm Helicobacter pylori infection of the Mongolian gerbil (18 months) as
      well as the effect of eradication therapy and the cag pathogenicity island on COX
      mRNA expression. COX mRNA levels were determined by reverse transcription
      polymerase chain reaction. Pyloric channel ulcers were noted in one of 10 gerbils
      (10%) at 3 months, 33% at 6 months, 50% at 9 months, 17% at 10 months, 40% at 12
      months and 25% at 18 months after inoculation of parental strains. Nineteen of 21
      gerbils had successful H. pylori eradication and showed significant reduction of
      inflammation and no ulcerations. There were no significant differences in COX-1
      mRNA expression between the groups. COX-2 mRNA expression was significantly
      increased 1 and 3 months after inoculation and then decreased to basal levels. In
      control animals, COX-2 mRNA expression was significantly higher at 12 and 18
      months compared to younger animals. cagE knockout mutants did not induce gastric
      inflammation and induced significantly lower COX-2 mRNA expression compared to
      parental strains. COX-2 mRNA was induced early in H. pylori infection and then
      declined. COX-2 mRNA expression was also induced with aging.

PMID- 14705821
TI  - Gastric carcinogenesis by duodenal reflux through gut regenerative cell lineage.
AB  - To elucidate the histogenesis of gastric stump cancer, we performed an operation
      in rats to make all duodenal contents flow back into the glandular stomach. The
      subjects were 41 rats, and sequential morphological changes of the duodenogastric
      stoma and the incidence of stump cancers were studied. Serial sections around the
      stoma were studied with mucin stains such as paradoxical concanavalin A (Con A),
      galactose oxidase Schiff (GOS), and high-iron diamine-Alcian blue (HID-AB). An
      immunohistochemical study on cell proliferation with bromodeoxyuridine (BrdU) was
      also done. At week 30, pyloric gland type cells positive for Con A first appeared
      at the base of the intestinal crypts and the fundic glands adjacent to the
      anastomosis. These glands became large with time, resulting in formation of
      cystically dilated glands. These gland cells were partially stained with GOS, and
      then they retained a proliferative activity. These changes seemed to resemble
      "gastritis cystica profunda" in human remnant stomachs. At 50 and 80 weeks,
      adenocarcinomas were observed in 4 of 10 rats (40.0%) and in 16 of 21 rats
      (76.2%), respectively. We have noted that the early change of cystic
      proliferation of mucous glands resembled the so-called "ulcer associated cell
      lineage (UACL)" described by others, but our characteristic finding was not only
      pyloric but also foveolar metaplasia. This pyloric-foveolar metaplasia
      subsequently led to development of glands with intestinal-type goblet cells,
      which looked like incomplete intestinal metaplasia. This sequence was different
      from UACL, and very recently, we proposed a concept of "gut regenerative cell
      lineage (GRCL); from pyloric-foveolar to with goblet cell metaplasia in
      regeneration," common to all parts of the gut, and the stump cancer appeared to
      arise from GRCL.

PMID- 14705822
TI  - Differential action of growth hormone in irradiated tumoral and nontumoral
      intestinal tissue.
AB  - Growth hormone (GH) protects the intestines from antitumoral therapy, but it is
      not known whether or not the tumor is also protected in vivo. The aim of the
      present work was to determine whether GH administration modifies the response by
      a colonic adenocarcinoma to radiation in vitro and in vivo. BDIX rats were
      implanted with a colonic adenocarcinoma and two weeks later GH treatment was
      started. Animals were then irradiated, and four days later samples from the
      intestines and tumor were taken for analysis. In vitro assays were performed in
      parallel to confirm the effects observed in vivo. GH reduced radiation-induced
      intestinal injury by improving proliferation and reducing apoptosis and p53
      expression. However, tumor proliferation was reduced by GH while apoptosis and
      p53 expression remained unchanged. A similar response was observed in vitro.
      Thus, GH administration before radiotherapy protects the intestines but not the
      implanted adenocarcinoma in the rat.

PMID- 14705823
TI  - Expression of intercellular adhesion molecule-1 (ICAM- 1) during ischemia
      reperfusion in human liver tissue allograft: image analysis by confocal laser
      scanning microscopy.
AB  - We studied and quantified the effect of ischemia-reperfusion on expression of
      intercellular adhesion molecule-1 (ICAM-1) on sinusoidal endothelial cells and
      hepatocyte plasma membranes by means of confocal laser scanning microscopy
      imaging. We found that ischemia induced an increase in ICAM-1 expression on
      sinusoidal endothelial cells and hepatocytes. After reperfusion, ICAM-1
      expression was increased on sinusoidal endothelial cells, whereas it was
      unmodified on hepatocytes. On the other hand, ICAM-1 expression was not
      correlated to ischemia-reperfusion liver injury. Therefore, hepatocellular
      ischemia-reperfusion injury could be induced by other causes than immune-mediated
      damages.

PMID- 14705825
TI  - Combined treatment with ursodeoxycholic acid and pioglitazone in a patient with
      NASH associated with type 2 diabetes and psoriasis.

PMID- 14705824
TI  - Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence
      and correlates.
AB  - Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD)
      were tested for non-organ-specific autoantibodies (NOSA) by indirect
      immunoflorescence. Indices of insulin resistance and biochemical and
      anthropometric parameters were assessed. The overall prevalence of anti-nuclear
      antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial
      antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4
      (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were
      older (P < 0.01) and mostly females (63.3%). No significant difference was found
      in the age-corrected parameters studied, except for copper and ceruloplasmin,
      which was more elevated in NOSA-positive patients. The subset of high titer
      (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin
      resistance than ANA-negative patients. In contrast, SMA-positive patients had
      higher gammaglobulin and significantly lower insulin resistance as compared to
      high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative
      patients, liver biopsy disclosed features of overlapping NASH with autoimmune
      hepatitis, partially responding to diet combined with steroid treatment. In
      conclusion, NOSA positivity in NAFLD is more prevalent than in the general
      population. High-titre ANA but not SMA positivity is associated with insulin
      resistance.

PMID- 14705826
TI  - Intrasphincteric nitric oxide reduces sphincter of Oddi motility in an endoscopic
      porcine model.
AB  - Nitric oxide (NO), a potent nonadrenergic, noncholinergic mediator of
      gastrointestinal smooth muscle, causes relaxation of the category I pump like
      sphincter of Oddi (SO) (eg, opossum, rabbit) and category II resistor like SO
      (eg, pig, human). Topical administration of a NO donor induces SO relaxation in
      humans, and parenteral administration of sodium nitroprusside (SNP) decreases
      sphincter contractility in pig SO. The aim of this study is to evaluate the
      effect of intrasphincteric SNP injection on pig SO. Under general anesthesia, two
      pigs received intrasphincteric saline injection (1 ml) and six pigs received
      intrasphincteric SNP (0.5 microg/ml) injection into the SO. All injections were
      administered into the major papilla using a 5-mm sclerotherapy needle through the
      duodenoscope. Endoscopic biliary manometry was performed using the standard
      station pull-through technique and SO pressures were recorded before and after
      injection. Intrasphincteric saline injection did not significantly change the
      mean SO motility index (MI) (197 vs 198). However, intrasphincteric SNP reduced
      both the mean SO basal pressure (P = 0.002) and the mean SO MI (226 vs 109; P =
      0.002). The effect of intrasphincteric SNP lasted up to 45 min and did not cause
      significant lowering of systemic blood pressure. This is the first study to
      demonstrate that intrasphincteric SNP results in significant reduction in both SO
      basal pressure and SO MI in the porcine model. The endoscopic intrasphincteric
      administration of NO donor drugs is technically feasible and without observed
      systemic side effects.

PMID- 14705827
TI  - Pancreatitis and duodenitis from sarcoidosis: successful therapy with
      mycophenolate mofetil.

PMID- 14705828
TI  - Stimulating effect of glucocorticosteroids on intestinal fructose transport in
      rats is increased by feeding a saturated fatty acid diet.
AB  - Glucocorticosteroids enhance absorptive functions of the intestine. This study
      was undertaken to assess the influence of budesonide (BUD), prednisone (PRED), or
      control vehicle in rats fed either a saturated fatty acid diet (SFA) or a
      polyunsaturated fatty acid diet (PUFA), on the uptake of sugars. Steroids
      increased the uptake of fructose, and these effects were greater with SFA than
      PUFA. No effect on the abundance or the expression of the mRNAs of SGLT1, GLUT5,
      or GLUT2 was observed, and yet immunohistochemistry staining in the jejunum for
      SGLT1 and GLUT5 was greater in SFA than in PUFA. The early response genes and
      proglucagon expression was enhanced in the ileum of animals fed SFA and given
      control vehicle. Steroids increased the ileal proglucagon mRNA. In summary, (1)
      PRED and BUD enhance the uptake of fructose, (2) this enhancement may be
      increased further by feeding SFA, and (3) signaling may involve early response
      genes and proglucagon.

PMID- 14705829
TI  - Benign solitary cecal ulcer: a case report and review of the literature.

PMID- 14705830
TI  - Management of splenic hydatid cysts by percutaneous drainage.

PMID- 14705831
TI  - Eosinophilic gastroenteritis: review of the literature.

PMID- 14705832
TI  - Self-rated quality of life in celiac disease.
AB  - As much as 1% of the gluten-consuming world is gluten-intolerant. New screening
      methods are increasingly identifying gluten intolerance in individuals previously
      free from health problems. The often-abrupt major change in diet may adversely
      affect the patient's quality of life. Our aim was to evaluate self-perceived
      quality of life in a large cohort of adult celiac patients after at least one
      year of a gluten-free diet. In all 581 members (410 females) of five regional
      celiac societies were on a gluten-free regimen for at least one year. In this
      cross-sectional study, a modified version of the Zung Self-Rating Depression
      Scale was administered to the 581 patients from five Italian regions. Most
      patients correctly defined celiac disease, and compliance with the gluten-free
      diet was high, although reporting bias cannot be excluded. Most felt well (83.6%
      "very well" and "well"); consequently, anxiety and depression scores were low.
      Happiness also scored low. Most participants did not feel that a gluten-free life
      differentiated them from the general population. Women and patients diagnosed
      after 20 years of age had better dietary compliance, but more problems in their
      social life. Happiness scores were higher in patients diagnosed before 20 years
      of age. Anxiety and depression were infrequent in this group; however, anxiety
      was frequently related to feeling different from the general population, and
      depression to an unsatisfactory sexual life. In conclusion, celiac disease does
      not appear to be associated to a low level of self-perceived quality of life in
      members of the Italian Celiac Society.

PMID- 14705833
TI  - Extrahepatic biliary schwannoma.
AB  - Schwannoma (neurilemoma or neurinoma) rarely develops in the biliary tract. We
      report here a case of extrahepatic biliary schwannoma found in a 47-yr-old
      Japanese woman presenting with obstructive jaundice. The radiological imaging
      studies were suggestive of nonepithelial tumor involving the common bile duct.
      The patient underwent tumor resection. The tumor extended inward and outward from
      the wall of the common bile duct in the shape of a dumbbell. The extraductal
      tumor was solid with microcystic changes, while the intraductal lesion presented
      cystic changes. Microscopically, the tumor was predominantly composed of spindle
      shaped cells with nuclear palisading, and it contained lymphoid aggregates.
      Immunohistochemically, the tumor cells were positive for S-100 protein. The final
      diagnosis was benign schwannoma of the common bile duct. The tumor differed from
      usual soft tissue schwannoma and closely resembled gastrointestinal schwannoma.

PMID- 14705834
TI  - Guideline for the out-of-hospital management of human exposures to minimally
      toxic substances.
AB  - All substances are capable of producing toxicity, so nothing is completely non
      toxic. Minimally toxic substances are those which produce little toxicity, minor
      self-limited toxicity, or clinically insignificant effects at most doses.
      Examples include silica gel, A&D ointment, chalk, lipstick, and non-camphor lip
      balms, watercolors, hand dishwashing detergents, non-salicylate antacids
      (excluding magnesium or sodium bicarbonate containing products), calamine lotion,
      clay, crayons, diaper rash creams and ointments, fabric softeners/sheets, glow
      products, glue (white, arts, and crafts type), household plant food, oral
      contraceptives, pen ink, pencils, starch/sizing, throat lozenges without local
      anesthetics, topical antibiotics, topical antifungals, topical steroids, topical
      steroids with antibiotics, and water-based paints. Minimally toxic exposures have
      the following characteristics: (1) The information specialist has confidence in
      the accuracy of the history obtained and the ability to communicate effectively
      with the caller. (2) The information specialist has confidence in the identity of
      the product(s) or substance(s) and a reasonable estimation of the maximum amount
      involved in the exposure. (3) The risks of adverse reactions or expected effects
      are acceptable to both the information specialist and the caller based on
      available medical literature and clinical experience. (4) The exposure does not
      require a healthcare referral since the potential effects are benign and self
      limited. However, decisions regarding patient disposition should take into
      account the patient's intent, symptoms, and social environment. In addition,
      individual patient circumstances (e.g., pregnancy, pre-existing medical
      conditions, therapeutic interventions) need to be considered. Minimally toxic
      exposures may vary in route (dermal, inhalation, ingestion, ocular), chronicity
      (acute, chronic), and substance composition (single or multi-ingredient, single
      or multiple product). Future categorization of substances as "minimally toxic"
      should be based on a process involving review of current knowledge, a thorough
      analysis of poisoning experience, and prospective validation.

PMID- 14705835
TI  - Suspected pediatric ingestions: effectiveness of immunoassay screens vs. gas
      chromatography/mass spectroscopy in the detection of drugs and chemicals.
AB  - Rapid and accurate analytical testing can be of great value when determining
      treatment for pediatric patients suspected of ingesting an unknown chemical.
      Though often overlooked, gas chromatography/mass spectroscopy (GC/MS) can be a
      valuable resource in emergency toxicology testing. In a recent 24-month period
      (July 1999-June 2001), the Analytical Toxicology Laboratory at the University of
      Mississippi Medical Center, Jackson, MS, compared the results of GC/MS analysis
      to results obtained by immunoassay testing. The laboratory tested 139 urine
      samples referred for STAT toxicology testing from the hospital's Pediatric
      Emergency Department. All samples were tested in parallel using an immunoassay
      technique (EMIT) and GC/MS. With analysis by immunoassay, 17.3% of the samples
      were positive for a drug of abuse. The number of positive drug classes ranged
      from 0 to 2 per sample (mean 0.17 +/- 0.43) using immunoassay. With analysis by
      GC/MS, drugs were detected in 88.5% of the samples. The number of drugs detected
      ranged from 0 to 11 per sample (mean 2.2 +/- 1.8) with GC/MS. A total of 64
      different pharmaceuticals were identified by GC/MS. This study shows that
      analysis by GC/MS offers the clinician a more comprehensive view into the
      exposure of the pediatric patient presenting with an unknown chemical ingestion.

PMID- 14705836
TI  - Emergence of imported ciguatera in Europe: report of 18 cases at the Poison
      Control Centre of Marseille.
AB  - BACKGROUND: Ciguatera is a disease caused by the ingestion of fish containing the
      toxins of Gambierdiscus toxicus. This dinoflagellate is frequently found in
      damaged coral reef systems. Previously rare in Europe, this disease entity is now
      seen in tourists returning from tropical countries. CASE SERIES: Eighteen
      patients were examined between 1997 and 2002. Nine poisonings occurred in
      Atlantic Ocean islands, eight in Pacific Ocean islands, and one in the Egyptian
      Red Sea coast. Gastrointestinal signs were always present in the Atlantic areas,
      but were less severe or absent in the Pacific areas. All patients had sensory
      disturbances, and two of them had motor disturbances affecting the respiratory
      muscles and leading to the death of a 73-year-old man in Cuba. The 17 surviving
      patients returned to France and for 2 to 18 months suffered from arthralgias,
      myalgias, or pruritus. CONCLUSION: Ciguatera is a newly imported intoxication in
      Europe. As the number of international tourists grows each year, this type of
      poisoning will be seen more frequently. Furthermore, as the condition of coral
      reefs declines around the world and the prevalence of G. toxicus increases,
      physicians in non-tropical countries should be prepared to manage such poisoned
      patients.

PMID- 14705837
TI  - Volatile substance and other drug abuse inhalation in Spain.
AB  - OBJECTIVE: Inhalant misuse is the intentional inhalation of volatile substances
      in order to obtain euphoric, disinhibiting, and exciting effects. Solvents,
      glues, adhesives, paints, varnishes, paint removers, dry cleaning agents, spray
      paints, nail polish removers, typewriter correction fluids, and aerosol
      propellants are common sources of volatile substance abuse. In recent years the
      abuse of inhalant substances, not only among those who abuse other drugs but also
      in teenagers and younger children, has been reported. We reviewed retrospectively
      the cases of inhalant misuse reported to the Spanish Poison Control Center.
      METHODS: Human intoxications from abuse of inhalant substances registered by our
      service from 1991 to 2000 were studied. Data analyzed were relative to age,
      gender, signs and symptoms, drug dependence antecedents, and severity of symptoms
      of the patients. The type of product and composition were also investigated.
      RESULTS: During the study period 109 cases of patients aged from 8 to 50 years
      were collected. A percentage of 36.6% was less or equal to 20 years old. Seventy
      percent corresponded to males. Of the patients, 11% presented dependence
      antecedents to other abuse drugs and 72.5% were symptomatic. In the symptomatic
      exposures clinical features affected the following systems: CNS (62.8%),
      gastrointestinal (8.1%), cardiovascular (8.1%), respiratory (2.9%), peripheral
      nervous system (1.1%), renal (1.1%), haematological (1.1%), hepatic (1.7%), and
      other (13.1%). The commercial products more frequently inhaled were solvents
      (34.9%) and glues/adhesives (22.9%). We noted the use of medicines with ethyl
      chloride-local anaesthetic (8.3%), three cases with aerosol bronchodilator (with
      fluorocarbons as propellants), and one case of xylazine inhalation. The
      composition most often involved was aromatic hydrocarbons (46.9%), halogenated
      hydrocarbons (16.5%), aliphatic hydrocarbons (11.4%), ketones (10.1%), local
      anaesthetic (ethyl chloride) (8.4%), ethers (2.5%), nitrous oxides (2.5%), and
      aliphatic nitrites (1.7%). The calls received were 59.6% from health care units
      and 22% from general public. Only 14% of cases were at home and 48% had moderate
      to severe clinical effects. Acute intoxications occurred in 82% of cases.
      CONCLUSIONS: Inhalation of volatile substance as abuse drugs has been detected in
      different age groups, including very young people. Although the principal source
      was industrial products, the use of drugs such as local anaesthetics and aerosol
      broncodilators was also detected. Based on epidemiological studies in the Spanish
      population (essentially adolescents and childhood) together with the ability of a
      Poison Center to detect sentinel-events, the community and authorities should
      develop strategies to prevent these exposures and the later use of other
      substances of abuse. In fact, recently a Law on Drug Dependences and Other
      Addictive Alterations has been approved in Madrid in order to take precautionary
      measures.

PMID- 14705838
TI  - Scorpion envenomations in young children in central Arizona.
AB  - INTRODUCTION: Centruroides sculpturatus, also known as Centruroides exilicauda or
      bark scorpion, is the only scorpion native to the United States whose venom
      produces a potentially life-threatening illness, particularly in children.
      OBJECTIVES: To describe the distribution of the severity grades following
      scorpion envenomations, the onset of clinical signs and symptoms, the time to
      deterioration, and side effects of antivenom treatment in children < or = 2 yrs
      of age. METHODS: Prospective case-series with the following inclusion criteria of
      presumed scorpion envenomation, witnessed scorpion or signs and symptoms
      consistent with envenomation, patient age < or = 2 yrs, and the call was received
      by the poison center. After data were entered prospectively, a reviewer who was
      blinded as to the purpose of the study reviewed the charts. A second reviewer
      examined 10% of the charts for accuracy in coding. Envenomation severity grades
      were based on a previously described scorpion grading scale and were correlated
      with admission rates, clinical deterioration, and outcomes. Descriptive
      statistics (STATA & EXCEL) were used. RESULTS: Of the 491 charts, 483 (98%) had
      adequate information available. The mean age was 20.8 [range 2-24] months with
      133 patients (27.5%) presenting to an emergency department (ED), 86 patients
      (17.8%) received antivenom, and 25 patients (5.2%) were admitted. The p-value for
      kappa and the 95% confidence interval (CI) for interobserver reliability kappa
      score was 0.69 with CI (0.44-0.95). The grade distributions were Grade I = 343
      cases (71%), Grade II = 8 cases (1.7%), Grade III = 49 cases (10.1%), and Grade
      IV = 83 cases (17.2%). The mean time to advancement of grade was 14 min (95% CI
      [10.97,17.06], 99% CI [10.04,18.03]) and the median time was < 1 min (range 0-140
      min). Twenty-five patients (5.2%) were admitted, of which 13 were Grade III and
      12 were Grade IV. Three patients (0.6% of total), all Grade IV envenomations,
      were intubated (95% CI [0.0021-0.0181] or an upper limit of 8.7 patients).
      Antivenom was administered to 86 patients (17.8%). The mean time of abatement of
      symptoms following antivenom was 31 [95% CI 10-82] min vs. 22.2 h [95% CI 12-46].
      There was one acute reaction (rash) to antivenom administration and 49 cases
      (57%) of serum sickness. CONCLUSIONS: Clinical progression following scorpion
      envenomation in children < or = 2 yrs old occurred on average within 14 min of
      envenomation with onset almost immediately. Serum sickness occurred in 57% of
      toddlers receiving antivenom and typically lasted less than 3 days. Admissions
      were less common among patients receiving antivenom.

PMID- 14705839
TI  - Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation.
AB  - BACKGROUND: Occupational exposure to solvents may be associated with development
      and progression of tubulo-interstitial fibrosis and chronic renal failure.
      However, the cellular mechanisms by which this occurs remain elusive. MATERIALS
      AND METHODS: The cytotoxicity of proximal tubular cells (LLC-PK1) exposed to 106
      mg/mL of p-xylene or 92 mg/mL of toluene was compared with untreated controls
      using cell viability (MTS assay) and caspase-3 activity, with or without caspase
      3 selective inhibitor. RESULTS: Both compounds reduced cell viability and
      increased caspase-3 activation (P < 0.005). Inhibition of caspase-3 by the
      selective inhibitor DEVD-CHO prevented injury (P < 0.001) and inhibited solvent
      induced caspase-3 activation (P < 0.005). CONCLUSION: Inhibition of caspase-3,
      the critical caspase in the apoptosis process, prevents cell injury in LLC-PK1.
      This suggests that caspase-3 may play a pivotal role in solvent-induced proximal
      tubular cell injury.

PMID- 14705840
TI  - Do co-intoxicants increase adverse event rates in the first 24 hours in patients
      resuscitated from acute opioid overdose?
AB  - BACKGROUND: Patients frequently arrive in emergency departments (EDs) after being
      resuscitated from opioid overdose. Autopsy studies suggest that multidrug
      intoxication is a major risk factor for adverse outcomes after acute heroin
      overdose in patients. If this is true, there may be high-risk drug combinations
      that identify patients who require more intensive monitoring and prolonged
      observation. Our objective was to determine the impact of co-intoxication with
      alcohol, cocaine, or CNS depressant drugs on short-term adverse event rates in
      patients resuscitated from acute opioid overdose. METHODS: Data were extracted
      from the database of a prospective opioid overdose cohort study conducted between
      May 1997 and 1999. Patients were prospectively enrolled if they received naloxone
      for presumed opioid overdose. Investigators gathered clinical, demographic, and
      other predictor variables, including co-intoxicants used. Patients were followed
      to identify prespecified adverse outcome events occurring within 24 h, and
      multiple logistic regression was used to determine the association of concomitant
      drug use on short-term adverse event rates. RESULTS: Of 1155 patients studied, 58
      (5%) had pure opioid overdose and 922 (80%) reported co-intoxicants, including
      alcohol, cocaine, and CNS depressants. Overall, out of 1056 patients with known
      outcome status there were 123 major adverse events (11.6%) and 194 minor adverse
      events (18.4%). After adjustment for age, gender, HIV status, cardiovascular
      disease, pulmonary disease and diabetes, we found that coadministration of
      alcohol, cocaine, or CNS depressants, alone or in combination, was not associated
      with increased risk of death or adverse events during the 24 h follow-up period.
      CONCLUSION: In patients resuscitated from acute opioid overdose, short-term
      outcomes are similar for patients with pure opioid overdose and multidrug
      intoxications. A history of cointoxication cannot be used to identify high-risk
      patients who require more intensive ED monitoring or prolonged observation.

PMID- 14705841
TI  - Detection and quantitation of xenobiotics in biological fluids by 1H NMR
      spectroscopy.
AB  - NMR spectroscopic investigation can be applied to a large variety of xenobiotics
      in acute poisoning cases (therapeutic agents, pesticides, solvents, alcohols). In
      a salicylate poisoning case, the three major metabolites of acetylsalicylic acid-
      salicylic, salicyluric, and gentisic acids--have been detected in crude urine.
      Valproic acid as glucuronoconjugated form was identified in urine samples from
      two poisoned patients. Paraquat (Gramoxone) was identified by its two aromatic
      signals at 8.49 and 9.02 ppm and quantitated in urine of two acutely poisoned
      patients (985 and 500 micromol/L). In an intentional poisoning case with
      tetrahydrofuran, this compound was characterized by its resonances at 1.90 and
      3.76 ppm, and quantitated at 11.3 and 11.8 mmol/L in serum and urine samples,
      respectively. Methanol, ethylene glycol, and the corresponding metabolites
      formate and glycolate were detected in the same spectrum of serum samples from
      three poisoned patients. Detection and quantitation of many exogenous and
      endogenous compounds could be achieved by 1H HMR spectroscopy in biological
      fluids without any hypothesis on the chemical species.

PMID- 14705842
TI  - Arsenic toxicity from homeopathic treatment.
AB  - Homeopathic medicine is commonly believed to be relatively harmless. However,
      treatment with improperly used homeopathic preparations may be dangerous. CASE
      REPORTS: Case 1 presented with melanosis and keratosis following short-term use
      of Arsenic Bromide 1-X followed by long-term use of other arsenic-containing
      homeopathic preparations. Case 2 developed melanotic arsenical skin lesions after
      taking Arsenicum Sulfuratum Flavum-1-X (Arsenic S.F. 1-X) in an effort to treat
      his white skin patches. Case 3 consumed Arsenic Bromide 1-X for 6 days in an
      effort to treat his diabetes and developed an acute gastrointestinal illness
      followed by leukopenia, thrombocytopenia, and diffuse dermal melanosis with
      patchy desquamation. Within approximately 2 weeks, he developed a toxic
      polyneuropathy resulting in quadriparesis. Arsenic concentrations in all three
      patients were significantly elevated in integument tissue samples. In all three
      cases, arsenic concentrations in drinking water were normal but arsenic
      concentrations in samples of the homeopathic medications were elevated.
      CONCLUSION: Arsenic used therapeutically in homeopathic medicines can cause
      clinical toxicity if the medications are improperly used.

PMID- 14705843
TI  - An outbreak of food-borne illness due to methomyl contamination.
AB  - BACKGROUND: On December 26, 2002, 124 dinners took ill while eating lunch at a
      seafood restaurant in the town of Chiching in Kaohsiung municipality of Taiwan.
      Sixty-nine people were sent to the emergency departments of the Municipal
      Chiching Hospital and Yuan's General Hospital. METHODS: We analyzed the clinical
      symptoms, detailed food history, and ingested amount of each food from 59
      hospitalized adult patients and identified the source of the outbreak. RESULTS:
      The median latency period from beginning eating to first symptoms was 5 min.
      Twenty-six symptoms and signs were recorded. The most commonly reported clinical
      effects were general weakness (84%), ataxia (82%), dizziness (82%), vomiting
      (80%), sweating (75%), floating sensation (71%), headache (69%), dyspnea (69%),
      and blurred vision (67%). Thirty-one patients had residual symptoms 7 days after
      ingestion. Of the six residual symptoms reported, the most frequent ones were
      dizziness (40%), poor appetite and dry mouth (11%), and gastrointestinal
      disturbance (11%). The presence of residual symptoms correlated with the severity
      of the initial complaints (p < 0.01). Almost all patients ate cooked rice (93%)
      and leaf vegetable stir-fried with crab claw (93%). The amount of each food eaten
      by the patients was not associated with the severity of symptoms (p > 0.05). High
      levels of methomyl in leaf vegetables of "leaf vegetables stir-fried with crab
      claws" (380 ppm) and fried mussels (1113 ppm) were found by the Food Inspection
      Center at the Department of Health. The food history and chemical analysis of the
      poison indicated methomyl was the cause of this outbreak. Twenty-four patients
      recovered completely within 7 days. CONCLUSION: Food-related methomyl
      intoxication produced a rapid onset of significant clinical toxicity in 124
      individuals. Based on the analysis of 55 adult patients, the most common effects
      were gait ataxia, dizziness, generalized weakness, and vomiting.

PMID- 14705844
TI  - Comparison of the fatal toxicity index of zopiclone with benzodiazepines.
AB  - BACKGROUND: Zopiclone is a hypnosedative structurally unrelated to the
      benzodiazepines but operating at the same receptor complex. Although zopiclone
      has been used in clinical practice for many years, relatively little is known of
      its relative toxicity in comparison with other hypnosedatives. METHOD: Deaths,
      where hypnosedatives were implicated, in New Zealand (NZ) in 2001 were identified
      from a chemical injury database. Prescription and aggregate defined daily dose
      (DDD) data forNZ in 2001 were obtained from a national prescribing database.
      Rates of death per prescription and DDD, and relative rates between individual
      hypnosedatives and benzodiazepines, and their respective 95% CI were calculated.
      RESULTS: Of the 200 poisoning deaths in NZ for 2001, 39 involved hypnosedatives,
      and zopiclone was involved in 12. Hypnosedatives were the sole agents in only one
      death and were the primary agents in eight deaths. Zopiclone was the sixth most
      commonly involved agent in poisoning deaths in NZ in 2001. The relative rate of
      death per prescription (95% CI) and DDD (95% CI) of zopiclone compared with
      benzodiazepines were 1.04 (0.49-2.05) and 0.59 (0.28-1.16), respectively. The
      relative rates of death per DDD (95% CI) for alprazolam and chlormethiazole
      compared with the other sedatives/anxiolytics were 6.2 (1.6-17.0) and 20.9 (2.5
      79.8) respectively. CONCLUSIONS: The fatal toxicity for zopiclone was not
      significantly different from that for benzodiazepines as a group when adjusted
      for usage, whereas alprazolam and chlormethiazole had greater toxicity.
      Hypnosedatives are contributory factors rather than primary substances in
      poisoning deaths.

PMID- 14705845
TI  - Crystal methamphetamine-associated cardiomyopathy: tip of the iceberg?
AB  - BACKGROUND: Crystal methamphetamine has become a drug of widespread use. Previous
      reports describe myocardial infarction, pulmonary edema, and aortic dissection
      related to methamphetamine use. Cardiomyopathy due to methamphetamine exposure
      has been rarely described. METHODS: We identified 1640 patients admitted in a 4
      yr period with a primary or secondary diagnosis of cardiomyopathy. We excluded
      patients with known cause of cardiomyopathy other than substance abuse. We found
      120 patients had a diagnosis of substance abuse, including 21 patients with
      methamphetamine use. We retrospectively reviewed the medical records of these 21
      crystal methamphetamine users. RESULTS: Nineteen (84%) underwent echocardiography
      with consistent findings of dilated cardiomyopathy and global ventricular
      dysfunction. Of five who had a nuclear myocardial perfusion study, none had
      evidence of ischemia or infarct. Of six who underwent cardiac catheterization,
      only one had evidence of coronary stenosis. CONCLUSION: Methamphetamine use
      appears to produce cardiomyopathy in some users. The pathogenesis is probably
      similar to that of cocaine and catecholamine-induced cardiomyopathy. Cellular,
      animal, and clinical data support the link between methamphetamine exposure and
      myocardial pathology.

PMID- 14705846
TI  - Acute topiramate toxicity.
AB  - Topiramate (Topamax) is an anti-epileptic medication for which acute toxicity is
      infrequently reported. A 5-yr-old girl, not previously taking topiramate,
      developed neurological symptoms after acute ingestion of this medication. She was
      intermittently agitated, complained of "not being able to feel anything,"
      demonstrated arching movements of the back, and perseverated upon questioning.
      Computerized tomography of the head and electroencephalography were both normal,
      and urine toxicology testing for drugs of abuse was negative. A serum topiramate
      level was 10.5 mcg/mL, confirming the ingestion. The patient was observed for 24
      h, over which time her symptoms completely resolved.

PMID- 14705847
TI  - Status epilepticus from an illegally imported Chinese rodenticide: "tetramine".
AB  - INTRODUCTION: The following case report demonstrates the severe consequences of
      refractory convulsive status epilepticus from an unfamiliar imported toxin,
      tetramethylenedisulfotetramine (TETS), and the difficulties of identifying the
      offending agent. CASE REPORT: A previously healthy 15-month-old girl was found by
      her parents playing with a white rodenticide powder brought from China. Fifteen
      minutes later, the child developed generalized seizures and was brought to an
      Emergency Department (ED). Her initial fingerstick blood glucose was 108 mg/dL.
      In the ED, the child was intubated for status epilepticus. Despite aggressive
      therapy with lorazepam, phenobarbital, and pyridoxine, she had 4 h of
      intermittent generalized seizure activity. She was extubated on the third
      hospital day, but appeared to have absence seizures and cortical blindness.
      Continuous electroencephalogram monitoring, performed weeks later, revealed
      severe diffuse cerebral dysfunction with multiple epileptogenic foci. The child
      remains developmentally delayed and is on valproic acid therapy for seizure
      control. Translation of the Chinese package labeling did not clarify its
      contents. Tetramethylenedisulfotetramine was finally confirmed by gas
      chromatography-mass spectrometry (GC-MS) in this rodenticide product and then
      quantified against a TETS standard that was synthesized in our laboratory.
      CONCLUSION: Tetramethylenedisulfotetramine is grouped with other "cage
      convulsants," such as picrotoxin, since they have a similar intercalating
      cyclical molecular structure and cause seizures through non-competitive gamma
      aminobutyric acid (GABA) antagonism. The oral lethal dose 50% (LD50) in humans is
      estimated to be as low as 100 microg/kg. Our patient has severe diffuse cerebral
      dysfunction likely secondary to prolonged seizure activity after exposure to
      TETS.

PMID- 14705848
TI  - Hydrocortisone-induced convulsions.
AB  - Glucocorticoids may indirectly cause convulsions by the induction of electrolytes
      abnormalities, severe hypertension, or severe hyperglycemia. These agents may
      rarely cause convulsions by a direct toxicity to the central nervous system
      (CNS). We describe a 23-yr-old patient with Crohn's disease in whom generalized
      convulsions developed on two occasions while receiving intravenous
      hydrocortisone.

PMID- 14705849
TI  - Massive venlafaxine overdose resulted in a false positive Abbott AxSYM urine
      immunoassay for phencyclidine.
AB  - CASE REPORT: A 13-yr-old girl overdosed on 48 x 150 mg venlafaxine (Effexor XR).
      She was taking venlafaxine regularly for depression. Her only other medications
      included topical Benzamycin and pyridoxine 50 mg daily for acne. The Abbott AxSYM
      assay was positive only for phencyclidine, but GC/MS did not confirm the presence
      of phencyclidine. Toxilab identified only one substance, confirmed by GC/MS as
      venlafaxine. A serum sample obtained 3 h after her ingestion revealed a
      venlafaxine concentration of 24460 ng/mL and an O-desmethylvenlafaxine
      concentration of 3930 ng/mL, confirming the massive acute overdose (therapeutic
      range of venlafaxine and O-desmethylvenlafaxine together is 250-750 ng/mL). Urine
      spiked with 4.2 mg/mL ofvenlafaxine and 0.7 mg/mL of O-desmethylvenlafaxine was
      interpreted as positive with the Abbott AxSYM fluorescent polarized immunoassay
      for phencyclidine (readout of 28 ng/mL). CONCLUSION: Venlafaxine may cause a
      false positive Abbott AxSYM phencyclidine assay when present in very high
      concentrations. Physicians should be aware of this potential reaction when
      interpreting urine drug immunoassays.

PMID- 14705850
TI  - Massive caffeine overdose requiring vasopressin infusion and hemodialysis.
AB  - INTRODUCTION: Massive caffeine overdose is associated with life-threatening
      hemodynamic complications that present challenges for clinicians. We describe the
      highest-reported serum concentration of caffeine in a patient who survived and
      discuss the first-reported use of vasopressin and hemodialysis in a caffeine
      poisoned patient. CASE REPORT: A 41-yr-old woman presented 3 h after ingesting
      approximately 50 g of caffeine. She subsequently underwent cardiopulmonary
      resuscitation and received multiple medications in an attempt to raise her blood
      pressure and control her heart rate without success. Vasopressin infusion
      increased her blood pressure to the point where hemodialysis could be performed.
      Despite ensuing multisystem organ failure, she survived and has made a complete
      recovery. CONCLUSION: Hemodialysis and vasopressin infusions may be of benefit in
      the management of caffeine-intoxicated patients who fail to respond to standard
      therapies.

PMID- 14705851
TI  - Hornet sting induced systemic allergic reaction and large local reaction with
      bulle formation and rhabdomyolysis.
AB  - A 41-yr-old, previously healthy male was stung once by a hornet. The patient had
      no history of allergy or hornet stings. Physical examination revealed swelling of
      the right side of his body with blister formation on the extremities.
      Rhabdomyolysis developed. Treatment included corticosteroids, antihistamines, and
      cyproheptadine. The patient was discharged without sequellae after being
      hospitalized for 7 days.

PMID- 14705852
TI  - Role of laboratory in the management of phenylbutazone poisoning.
AB  - We report a rare case of intentional overdose of phenylbutazone in a 15-yr-old
      female. The patient exhibited symptoms of phenylbutazone toxicity and the
      presence of the drug was confirmed by gas chromatography mass-spectrometry (GC
      MS) analysis of the initial urine sample. The patient underwent plasmapheresis to
      remove the drug from the circulation. Semiquantitation of sequential serum
      samples by GC-MS revealed elimination of phenylbutazone by day 5 of admission at
      which time the plasmapheresis was discontinued. Elevated blood urea nitrogen
      (BUN) and creatinine returned to normal. Analysis of biomarkers for liver
      necrosis and regeneration in sequential serum samples revealed the restoration of
      normal liver function by day 5. This case further confirms our previous
      observations that biomarkers for liver necrosis and regeneration can predict the
      outcome of patients with liver damage due to toxins.

PMID- 14705853
TI  - Irreversible ischemic hand following intraarterial injection of zolpidem powder.
AB  - Intraarterial injections of crushed oral formulations of drugs may cause acute,
      severe ischemia, and gangrene. A 24-yr-old woman developed severe ischemia of the
      right hand following arterial self-injection of a crushed zolpidem tablet. The
      first four digits of her right hand remained gangrenous even after treatment with
      heparinization, vasodilators, prostacyclin, and hyperbaric oxygen. Zolpidem
      tablets contain microcrystalline cellulose, an approved structural element in
      tablets for humans that has also been found to be a potent embolic agent.
      Microvascular embolization related to the microcrystalline cellulose may have
      contributed to the ischemia of the patient's hand.

PMID- 14705854
TI  - Topical treatments for hydrofluoric acid burns: a blind controlled experimental
      study.

PMID- 14705855
TI  - A fatal case of metformin poisoning.

PMID- 14705856
TI  - Mirtazepine overdose and miosis.

PMID- 14705857
TI  - Comment on "An analysis of glyphosate data from the California Environmental
      Protection Agency Pesticide Illness Surveillance Program".

PMID- 14705858
TI  - Comment on "Baclofen withdrawal following removal of an intrathecal baclofen pump
      despite oral baclofen replacement".

PMID- 14705859
TI  - Pathophysiological factors affecting CAR gene expression.
AB  - The body defends itself against potentially harmful compounds, such as drugs and
      toxic endogenous compounds and their metabolites, by inducing the expression of
      enzymes and transporters involved in their metabolism and elimination. The orphan
      nuclear receptor CAR (NR1I3 controls phase I (CYP2B, CYP2C, CYP3A), phase II
      (UGT1A1), and transporter (SLC21A6, MRP2) genes involved in drug metabolism and
      bilirubin clearance. Constitutive androstane receptor (CAR) is activated by
      xenobiotics, such as phenobarbital, but also by toxic endogenous compounds such
      as bilirubin metabolite(s). To better understand the inter- and intravariability
      in drug detoxification, we studied the molecular mechanisms involved in CAR gene
      expression in human hepatocytes. We clearly identified CAR as a glucocorticoid
      receptor (GR) target gene, and we proposed the hypothesis of a signal
      transduction where the activation of GR plays a critical function in CAR-mediated
      cellular response. According to our model, chemicals or pathophysiological
      factors that affect GR function should decrease CAR function. To test this
      hypothesis, we recently investigated the effect of microtubule disrupting agents
      (MIAs) or proinflammatory cytokines. These compounds are well-known inhibitors of
      GR transactivation property. MIAs activate c-Jun N-terminal kinase (JNK), which
      phosphorylates and inactivates GR, whereas proinflammatory cytokines, such as IL
      6 or IL1beta, induce AP-1 or NF-kB activation, respectively, leading to GR
      inhibition. As expected, we observed that these molecules inhibit both CAR gene
      expression and phenobarbital-mediated CYP gene expression in human hepatocytes.

PMID- 14705860
TI  - Early drug safety evaluation: biomarkers, signatures, and fingerprints.
AB  - When target organ toxicity arises in animal models during routine drug safety
      evaluation, it raises several key questions: Is this target organ toxicity
      related to the pharmacology? What is the mode of action (MOA)? Is the target
      organ toxicity relevant to humans? Pathology or prior knowledge of the compound
      class may provide clues on a possible MOA for toxicity. However, if this
      deductive approach yields no results, the inductive approach offered by new
      technologies can generate novel research leads. For example, toxicogenomics can
      generate a gene expression profile of the toxicity that can be compared with
      reference compounds or with other candidate drugs. Similarly, proteomic analysis
      of the protein profile at the toxic vs. the efficacious dose can provide clues on
      MOA for the toxicity and may allow differentiation of the pathways of the toxic
      response from those required for pharmacological activity.

PMID- 14705861
TI  - Clinical relevance of pharmacogenetics.
AB  - Pharmacogenetics fields of research was initially restricted to drug metabolism
      enzymes. It has recently progressed to drug transporters, receptors, and any kind
      of targets that can modulate drug response. This rapid extension of
      pharmacogenetics to all the different medical specialties is in close relation
      with the recent completion of the draft sequence of the human genome and the
      discovery that about 0.1% of its sequence is polymorphic. The goal of
      pharmacogenetics for the next years is clearly to determine the clinical
      consequences of these 2-3 million single nucleotide polymorphisms (SNPs). Things
      can be schematically divided in two situations. (1) Frequent SNPs (allele
      frequency > 10%) which have a low impact on drug response (odds ratios < 2), even
      combined with other SNPs in haplotype combinations. Such situations, which are by
      far the most frequent, have no clinical relevance for a single patient to predict
      its response to a particular drug. CYP3A and MDR1 allelic variants are good
      examples of such frequent situations. (2) Rare SNPs, which dramatically alter the
      expression or the activity of a target protein, can sometimes have a real
      clinical relevance (odds ratios > 5), usually to predict drug side effects. Only
      few examples, such as TPMT and CYP2C9 genetic polymorphisms, can illustrate this
      rare situation. Unfortunately, less than 1% of the population is concerned by
      these rare SNPs, and genotyping can only explain a small part of the variability
      of the response to a single drug. Beside the impressive mass of data available
      for pharmacogenetics, it is surprising to observe its poor development in routine
      medical practice. This discrepancy relies mainly on educational and
      methodological problems, which might be solved in the decade. To promote
      pharmacogenetics in routine medical practice, large prospective randomized trials
      are needed to demonstrate that pharmacogenetic orientated prescription can
      sometimes predict drug response without dramatic increase in costs.

PMID- 14705862
TI  - The human UDP-glucuronosyltransferases: structural aspects and drug
      glucuronidation.

PMID- 14705863
TI  - Regulation of drug and bile salt transporters in liver and intestine.
AB  - Major determinants of the bioavailability of drugs are the degree of intestinal
      absorption and the hepatic first-pass effect. Drugs need to overcome several
      membrane barriers before reaching the systemic circulation, each of which
      expresses an array of specialized transport proteins for drug uptake or efflux.
      The P-glycoprotein MDR1 (multidrug resistance gene product, ABCB1) is expressed
      at the apical surface of enterocytes, where it mediates the efflux of xenobiotics
      into the intestinal lumen before these can access the portal circulation.
      Increased expression of MDR1 reduces the bioavailability of MDR1 substrates such
      as digoxin, cyclosporin, and taxol. Numerous xenobiotics can induce the MDR1 gene
      through activation of the nuclear pregnane X receptor (PXR). This explains the
      risk for drug interactions that is inherent to pharmacotherapy with PXR ligands
      such as rifampin, phenobarbital, statins, and St. John's wort. Other PXR
      regulated genes include cytochrome P450 3A4, the digoxin and bile salt
      transporter Oatp2 (organic anion transporting polypeptide 2, Slc01a4) of the
      basolateral hepatocyte membrane, and the xenobiotic efflux pump Mrp2 (multidrug
      resistance associated protein 2, Abcc2) of the canalicular hepatocyte membrane. A
      second orphan nuclear receptor that is activated by xenobiotics is the
      constitutive androstane receptor (CAR), which induces Mrp2 and Mrp3 (Abcc3). The
      PXR and CAR are thus important "xenosensors" that mediate drug-induced activation
      of the detoxifying transport and enzyme systems in liver and intestine.

PMID- 14705864
TI  - Role of gene knockout and transgenic mice in the study of xenobiotic metabolism.
AB  - The role of P450s in xenobiotic metabolism, toxicity, and carcinogenicity has
      been studied for many years by using in vitro approaches and limited in vivo
      investigations. Genetic analysis to study the effects of xenobiotics in intact
      animals has only recently been carried out by use of gene knockout mice. Mice
      lacking expression of these enzymes have no or only modest phenotypes, indicating
      that their xenobiotic-metabolizing enzymes are not critical for mammalian
      development or physiological homeostasis. The null mice have been used to study
      the roll of xenobiotic-metabolizing enzymes in chemical toxicity and
      carcinogenicity. There are marked species differences in the expression and
      catalytic activities of P450s that metabolize xenobiotics, and this complicates
      the extrapolation of data obtained in rodents for use in drug development and
      human risk assessment. This is especially notable between mice and rats, commonly
      used experimental models, and humans. To begin to develop more predictive models,
      P450 humanized mice were produced and characterized by using genomic clones
      containing the complete coding and regulatory regions of genes, as transgenes.
      Humanized lines expressing CYP2D6 and CYP3A4 human P450 were characterized and
      found to accurately express human P450 proteins and catalytic activities at
      levels comparable to or higher than the corresponding activities found in human
      tissues. These novel mouse lines offer the opportunity to predict human drug and
      carcinogen metabolism and disposition and to search for endogenous substrates for
      human P450s.

PMID- 14705865
TI  - Chemical-induced apoptosis: formation of the Apaf-1 apoptosome.
AB  - Many environmental and therapeutic agents initiate apoptotic cell death by
      inducing the release of cytochrome c from the mitochondria, which activates Apaf
      1 (apoptotic protease-activating factor-1). This large (approximately 130kD)
      protein is a mammalian homologue of CED-4, an essential protein involved in
      programmed cell death in the nematode C. elegans. Cytochrome c activates Apaf-1,
      which oligomerizes to form an approximately 700-1400-kDa caspase-activating
      complex known as the Apaf-1 apoptosome. Caspase-9, an initiator caspase, is then
      recruited to the complex by binding to Apaf-1 through CARD-CARD (caspase
      recruitment domain) interactions to form a holoenzyme complex. Subsequently, the
      Apaf-1/caspase-9 holoenzyme complex recruits the effector caspase-3 via an
      interaction between the active site cysteine in caspase-9 and the critical
      aspartate, which is the cleavage site for generating the large and small subunits
      of caspase-3 that constitute the activated form of caspase-3. This initiates the
      caspase cascade that is responsible for the execution phase of apoptosis.
      Intracellular levels of K+, XIAP an inhibitor of apoptosis protein, and at least
      two mitochondrial released proteins, Smac/DIABLO and Omi/Htra 2 a serine
      protease, tightly regulate formation and function of the apoptosome. Thus, a
      number of physiological mechanisms ensure that the apoptosome complex is only
      fully assembled and functional when the cell is irrevocably committed to die. It
      is interesting that more recent studies show that a variety of small molecules
      can directly activate or inhibit caspase activation by interfering with the
      formation and function of the apoptosome complex. The cytotoxicity of many
      conventional chemotherapeutic drugs rests on their ability to induce apoptosome
      formation and apoptosis. Defects in this pathway can result in drug resistance,
      and the discovery that small molecules can directly activate or inhibit the
      apoptosome may provide new alternative treatments for cancer.

PMID- 14705866
TI  - The telltale structures of epoxide hydrolases.
AB  - Traditionally, epoxide hydrolases (EH) have been regarded as xenobiotic
      metabolizing enzymes implicated in the detoxification of foreign compounds. They
      are known to play a key role in the control of potentially genotoxic epoxides
      that arise during metabolism of many lipophilic compounds. Although this is
      apparently the main function for the mammalian microsomal epoxide hydrolase
      (mEH), evidence is now accumulating that the mammalian soluble epoxide hydrolase
      (sEH), despite its proven role in xenobiotic metabolism, also has a central role
      in the formation and breakdown of physiological signaling molecules. In addition,
      a certain class of microbial epoxide hydrolases has recently been identified that
      is an integral part of a catabolic pathway, allowing the use of specific terpens
      as sole carbon sources. The recently available x-ray structures of a number of
      EHs mirror their respective functions: the microbial terpen EH differs in its
      fold from the canonical alpha/beta hydrolase fold of the xenobiotic-metabolizing
      mammalian EHs. It appears that the latter fold is the perfect solution for the
      efficient detoxification of a large variety of structurally different epoxides by
      a single enzyme, whereas the smaller microbial EH, which has a particularly high
      turnover number with its prefered substrate, seems to be the better solution for
      the hydrolysis of one specific substrate. The structure of the sEH also includes
      an additional catalytic domain that has recently been shown to possess
      phosphatase activity. Although the physiological substrate for this second active
      site has not been identified so far, the majority of known phosphatases are
      involved in signaling processes, suggesting that the sEH phosphatase domain also
      has a role in the regulation of physiological functions.

PMID- 14705867
TI  - Knockout mice in xenobiotic metabolism.

PMID- 14705868
TI  - Progress towards prediction of human pharmacokinetic parameters from in vitro
      technologies.
AB  - This review provides an academic view of the current status on using in vitro
      systems for the prediction of human in vivo drug clearance and inhibition
      interaction potential. It stresses that although in vitro technology continues to
      develop in an impressive way and expectations are high within the pharmaceutical
      industry, the potential of prediction process is yet to be fully realized. The
      principles of scaling and modeling in vitro parameters have a sound base and have
      been validated by using animal tissue. However, it is clear that the
      comparatively simple standard approach developed and validated in animal systems,
      results in a high incidence of underprediction for parameters describing
      clearance and inhibition interaction potential when applied to humans. There are
      several challenges to our ability to interpret the human in vitro data that can
      now be so readily generated, in particular, accommodating the unusual kinetic
      properties characteristic of CYP3A4 substrates, namely, positive and negative
      cooperativity, in the assessment of inhibition potential.

PMID- 14705869
TI  - Clinical relevance of P-glycoprotein in drug therapy.
AB  - The drug efflux transporter P-glycoprotein (P-gp) is known to confer multidrug
      resistance in cancer chemotherapy. The P-gp is highly expressed in many types of
      tumor cells, as well as many normal tissues, including the apical surface of
      intestinal epithelial cells, and the luminal surface of capillary endothelial
      cells in the brain. Because of its expression and localization, it has been
      suggested that P-gp plays an important role in cancer chemotherapy, intestinal
      absorption, and brain uptake. This review addresses the significance of the role
      of P-gp in cancer chemotherapy, drug absorption, and brain uptake. Based on the
      clinical and animal studies with P-gp modulators, it has become apparent that the
      role of P-gp in multidrug resistance is far less important compared to other
      biological factors. Although P-gp is highly expressed in both intestinal
      epithelial cells and endothelial cells of brain capillaries and functions as an
      efflux transporter in both organs, the magnitude of P-gp's impact on intestinal
      absorption and brain uptake of drugs is quantitatively very different. From
      animal and clinical studies, it is evident that P-gp plays a very important role
      in CNS penetration of drugs, whereas the effect of P-gp on drug absorption is not
      as important as generally believed.

PMID- 14705870
TI  - Systemic acquired resistance in crop protection: from nature to a chemical
      approach.
AB  - Plant natural resistance to potential parasites is regulated by two fundamental
      mechanisms: the "nonhost" and the "gene-for-gene" resistance, respectively. The
      latter is relevant when a cultivar resistant (R) gene product recognizes an
      avirulence gene product in the attacking pathogen and triggers an array of
      biochemical reactions that halt the pathogen around the site of attempted
      invasion. To cope with virulent pathogens, plants may benefit by some temporary
      immunity after a challenge triggering such an array of defense reactions,
      following a localized necrotizing infection as a possible consequence of a
      hypersensitive response (HR). This process, mediated by accumulation of
      endogenous salicylic acid (SA), is called systemic acquired resistance (SAR) and
      provides resistance, to a certain extent even against unrelated pathogens, such
      as viruses, bacteria, and fungi, for a relatively long-lasting period. SAR may be
      more potently activated in plants pretreated with chemical inducers, most of
      which appear to act as functional analogues of SA. This review summarizes the
      complex aspects of SAR as a way to prevent crop diseases by activating the
      plants' own natural defenses. The following outline is taken: (1) introduction
      through the historical insight of the phenomenon; (2) oxidative burst, which
      produces high levels of oxygen reactive species in a way similar to the
      inflammation state in animals and precedes the HR to the pathogen attack; (3) SAR
      as a coordinate action of several gene products leading to the expression of
      defenses well beyond the time and space limits of the HR; (4) jasmonic acid (JA)
      and ethylene as other endogenous factors mediating a different pathway of induced
      resistance; (5) pathogenesis related proteins (PR proteins) de novo synthesized
      as specific markers of SAR; (6) exogenous inducers of SAR, which include both
      synthetic chemicals and natural products; (7) the pathway of signal transduction
      between sensitization by inducers and PR expression, as inferred by mutageneses,
      a process that is still, to a large extent, not completely elucidated; (8)
      prospects and costs; (9) final remarks on the state-of-the-art of the topic
      reflecting the chemical view of the author, based on the more authoritative ones
      expressed by the authors of the reviewed papers.

PMID- 14705871
TI  - Chemistry, biochemistry, and safety of acrylamide. A review.
AB  - Acrylamide (CH2=CH-CONH2), an industrially produced alpha,beta-unsaturated
      (conjugated) reactive molecule, is used worldwide to synthesize polyacrylamide.
      Polyacrylamide has found numerous applications as a soil conditioner, in
      wastewater treatment, in the cosmetic, paper, and textile industries, and in the
      laboratory as a solid support for the separation of proteins by electrophoresis.
      Because of the potential of exposure to acrylamide, effects of acrylamide in
      cells, tissues, animals, and humans have been extensively studied. Reports that
      acrylamide is present in foods formed during their processing under conditions
      that also induce the formation of Maillard browning products heightened interest
      in the chemistry, biochemistry, and safety of this vinyl compound. Because
      exposure of humans to acrylamide can come from both external sources and the
      diet, a need exists to develop a better understanding of its formation and
      distribution in food and its role in human health. To contribute to this effort,
      this integrated review presents data on the chemistry, analysis, metabolism,
      pharmacology, and toxicology of acrylamide. Specifically covered are the
      following aspects: nonfood and food sources; exposure from the environment and
      the diet; mechanism of formation in food from asparagine and glucose; asparagine
      asparaginase relationships; Maillard browning-acrylamide relationships; quenching
      of protein fluorescence; biological alkylation of amino acids, peptides,
      proteins, and DNA by acrylamide and its epoxide metabolite glycidamide; risk
      assessment; neurotoxicity, reproductive toxicity, and carcinogenicity; protection
      against adverse effects; and possible approaches to reducing levels in food.
      Further research needs in each of these areas are suggested. Neurotoxicity
      appears to be the only documented effect of acrylamide in human epidemiological
      studies; reproductive toxicity, genotoxicity/clastogenicity, and carcinogenicity
      are potential human health risks on the basis of only animal studies. A better
      understanding of the chemistry and biology of pure acrylamide in general and its
      impact in a food matrix in particular can lead to the development of improved
      food processes to decrease the acrylamide content of the diet.

PMID- 14705872
TI  - Quantitative determination of beta-carotene stereoisomers in fresh, dried, and
      solar-dried mangoes (Mangifera indica L.).
AB  - A rapid method for quantitative determination of beta-carotene, including cis
      isomers, in dried mango has been developed. Applicability of available methods to
      dried products was limited because of formation of artifacts caused by extraction
      and preparation. The analytical procedure was based on the extraction of
      carotenoids from dried mango mesocarp using a mixture of methanol and
      acetone/hexane, allowing the separation of disturbing fibers. No saponification
      was required. Furthermore, carotenoid determination by HPLC on a C30 stationary
      phase was achieved. This method was applied to determine beta-carotene and its
      stereoisomers in fresh, dried, and solar-dried mango slices of four cultivars.
      Drying resulted in a complete and partial degradation of xanthophylls and all
      trans-beta-carotene, respectively. Isomerization was shown to depend on the
      drying process. Whereas conventionally dried mangoes were characterized by
      elevated amounts of 13-cis-beta-carotene, solar-dried mango slices contained
      additional amounts of the 9-cis-isomer. Calculation of vitamin A values was based
      on the real amount of the beta-carotene stereoisomers and ranged from 113 to 420
      and from 425 to 1010 RE/100 g for fresh and dried mango slices, respectively.

PMID- 14705873
TI  - A semi-pilot-scale procedure for isolating and purifying soybean (Glycine max)
      lectin.
AB  - Availability of gram quantities of purified soybean lectin (SBL) to scientists
      will foster discovery of novel biomedical applications of the lectin and provide
      the opportunity to investigate the antinutritional effects of SBL in soybean
      consuming food animals and poultry. Therefore, a semi-pilot-scale procedure for
      isolating and purifying SBL was designed. Defatted soyflour was extracted
      overnight with 0.9% NaCl at 4 degrees C. The extract obtained was filtered (0.45
      microm membrane) and subjected to affinity chromatography using a column
      containing N-acetyl-D-galactosamine resin that is specific for SBL. Bound SBL was
      eluted off the column with 0.14 M galactose solution. The eluent was
      ultrafiltered (30 kDa), and the resulting solution (SBL and water) was freeze
      dried. Electrophoretic analysis and hemagglutination assay revealed that the
      freeze-dried SBL was similar to Sigma-grade SBL in purity and activity (35 and 33
      HU/mg protein, respectively). The procedure yielded 141 mg of SBL/100 g of
      soyflour.

PMID- 14705874
TI  - Anthocyanin glycosides from berry fruit are absorbed and excreted unmetabolized
      by both humans and rats.
AB  - Anthocyanins, the red/blue pigments found in plants, are polyphenolic compounds
      consumed by humans and are part of a normal diet. Recent studies have shown that
      anthocyanins have substantial bioactivity including antioxidant activity and
      therefore may have beneficial effects on human health. Anthocyanins are a group
      of over 500 compounds of diverse structures containing different core phenolic
      aglycons and conjugated with sugars in a variety of glycosylation patterns. In
      this study, we have investigated the bioabsorption of 15 anthocyanins with
      structures containing different aglycons and conjugated sugars extracted from
      blueberry, boysenberry, black raspberry, and blackcurrant in both humans and
      rats. Intact and unmetabolized anthocyanins were detected in urine of rats and
      humans following dosing for all molecular structures investigated, thus
      demonstrating that anthocyanins with diverse molecular structure and from
      different dietary sources are bioavailable at diet relevant dosage rates. In
      addition, the relative concentrations of anthocyanins detected in urine following
      dosing varied, indicating that differences in bioavailability are due to
      variations in chemical structure. Our results suggest that the nature of the
      sugar conjugate and the phenolic aglycon are both important determinants of
      anthocyanin absorption and excretion in rats and humans.

PMID- 14705875
TI  - Phytochemistry of wild populations of Panax quinquefolius L. (North American
      ginseng).
AB  - A survey of the phytochemistry of Panax quinquefolius L. (North American ginseng)
      collected from wild populations in Ontario, Quebec, Maine, Vermont, and Wisconsin
      was undertaken. Reverse-phase HPLC was used to determine the natural variation of
      levels of ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd and their total in leaf,
      stem, and root of authentic wild-grown material. The totals in roots varied from
      1 to 16%, with the greatest number of individual samples having 4-5% total
      ginsenosides. The lack of ginsenoside Rf in roots of authentic wild populations
      confirmed its status as a phytochemical marker differentiating American and Asian
      ginseng. Ten geographically isolated wild populations were collected, and several
      showed significant variation in the levels of major ginsenosides. There was no
      statistical difference in mean ginsenoside content between wild and cultivated P.
      quinquefolius roots at 4 years of age, suggesting there is no phytochemical
      justification for wild crafting. Baseline data on total ginsenoside levels for
      authentic wild P. quinquefolius reported here provide reference levels for
      quality assurance programs.

PMID- 14705876
TI  - Soy leaf lowers the ratio of non-HDL to HDL cholesterol in hamsters.
AB  - The present study was to examine effect of soy leaf powder (SLP) and soy leaf
      ethanol extract (SLEE) on serum lipoproteins in hamsters. The control group was
      fed a semisynthetic diet containing 0.1% cholesterol, while the tested groups
      were maintained on the same diet but supplemented with 3% SLP or the equivalent
      amount of SLEE derived from 3% SLP for 4 weeks. SLP supplementation led to a
      trend of lowering serum total cholesterol (TC) and nonhigh density lipoprotein
      cholesterol (non-HDL-C), with HDL-C being unaffected, whereas incorporation of
      SLEE into the diet led to an elevated level of HDL-C and a lower level of non-HDL
      C with TC being unchanged. Both SLP and SLEE supplementation caused favorably a
      decrease in the ratio of non-HDL-C to HDL-C. The present results demonstrate that
      not only soybean seeds but also soy leaves are cardioprotective, by favorably
      modulating serum lipid profile.

PMID- 14705877
TI  - Effect of selected phytotoxins from Guanomyces polythrix on the calmodulin
      dependent activity of the enzymes cAMP phosphodiesterase and NAD-kinase.
AB  - The effect of a series of phytotoxins isolated from the fungus Guanomyces
      polytrix on calmodulin (CaM)-dependent nicotinamide adenine dinucleotide kinase
      (NADK) and CaM-dependent cyclic nucleotide phosphodiesterase (PDE) activities was
      investigated. The results indicated that (2S,3S)-5-hydroxy-6,8-dimethoxy-2,3
      dimethyl-4H-2,3-dihydronaphtho[2,3-b]-pyran-4-one, (2S,3S)-5-hydroxy-6,8,10
      trimethoxy-2,3-dimethyl-4H-2,3-dihydro-naphtho[2,3-b]-pyran-4-one, (2S,3R)-5
      hydroxy-6,8-dimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one,
      (2S,3R)-5-hydroxy-6,8,10-trime-thoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]
      pyran-4-one, 5-hydro-xy-6,8-dimethoxy-2,3-dimethyl-4H-naphtho[2,3-b]-pyran-4-one,
      rubrofusarin B, and ergosta-4,6,8(14),22-tetraen-3-one inhibited the activation
      of both target enzymes in the presence of CaM. On the other hand, (2S)-5-hydroxy
      6,8-dimethoxy-2-methyl-4H-2,3-dihydronaphtho[2,3-b]-pyran-4-one and (2S)-5
      hydroxy-6,8,10-trimethoxy-2-methyl-4H-2,3-dihydronaphtho-[2,3-b]-pyran-4-one
      inhibited the activation of PDE and the basal activity of NADK. Thus, these
      phytotoxins are CaM inhibitors and may exert their phytotoxic action by
      inhibiting the CaM-dependent process, although they could also interfere with
      other cellular metabolic phenomena. This is the first report of the use of the
      NADK assay to detect or quantify CaM inhibitors, and it could be a valuable tool
      for studying those CaM isoforms regulating NADK.

PMID- 14705878
TI  - Antioxidant properties and composition of aqueous extracts from Mentha species,
      hybrids, varieties, and cultivars.
AB  - Water-soluble extracts from the Mentha species M. aquatica L. and M. haplocalyx
      Briq., the hybrids M. x dalmatica L. and M. x verticillata L., the varieties M.
      arvensis var. japanensis [M. arvensis L. var. piperascens Holmes ex Christ] and
      M. spicata L. var. crispa Benth, and M. x piperita L. "Frantsila", M. "Morocco",
      and M. "Native Wilmet" cultivars were screened for potential antioxidative
      properties. These properties included iron(III) reduction, iron(II) chelation,
      1,1-diphenyl-2-picrylhydrazyl radical scavenging, and the ability to inhibit
      iron(III)-ascorbate-catalyzed hydroxyl radical-mediated brain phospholipid
      peroxidation. Total phenol content and qualitative and quantitative compositional
      analyses of each extract were also made. The extracts demonstrated varying
      degrees of efficacy in each assay, with the M. x piperita "Frantsila" extract
      being better than the other extracts, except for ferrous iron chelation. With the
      exception of iron chelation, it appeared that the level of activity identified
      was strongly associated with the phenolic content.

PMID- 14705879
TI  - Neuroprotective effect of rough aster butanol fraction against oxidative stress
      in the brain of mice challenged with kainic acid.
AB  - The neuroprotective effect of the butanol fraction from the methanol extract of
      Aster scaber Thunb. (rough aster butanol fraction) on oxidative damage in the
      brain of mice challenged with kainic acid was examined using behavioral signs and
      biochemical parameters of oxidative stress. The rough aster butanol fraction (0.4
      1.0 g/kg) was administered to ICR male mice, 6-8 weeks, through a gavage for 4
      days consecutively, and on the third day, kainic acid (50 mg/kg) was ip
      administered. When compared to the vehicle-treated control, no significant
      changes in body and brain weight were observed in mice administered the rough
      aster butanol fraction. Administration of kainic acid only, causing a lethality
      of approximately 54%, resulted in a significant decrease of total glutathione
      level and an increase of the thiobarbituric acid-reactive substances (TBARS)
      value in brain tissue. When the rough aster butanol fraction was examined for
      neuroprotective action, the rough aster butanol fraction (0.4 g/kg) alleviated
      the lethality (25%) of kainic acid and the behavioral sign of its neurotoxicity.
      Moreover, administration of the rough aster butanol fraction at a dose of 0.4
      g/kg restored the glutathione level in the cytosolic portion of brain homogenate
      to approximately 80% (p < 0.05). Also, the rough aster butanol fraction (0.4
      g/kg) led to a significant reduction of kainic acid-induced increase of TBARS
      value. In addition, the glutathione peroxidase activity was restored
      significantly (p < 0.05) in the cytosolic portion of brain homogenate, whereas
      glutathione reductase activity was not. On the basis of these results, the rough
      aster butanol fraction is suggested to contain a functional agent to prevent
      oxidative stress in the brain of mice.

PMID- 14705880
TI  - Grape polyphenol resveratrol and the related molecule 4-hydroxystilbene induce
      growth inhibition, apoptosis, S-phase arrest, and upregulation of cyclins A, E,
      and B1 in human SK-Mel-28 melanoma cells.
AB  - The effect of the naturally occurring polyphenol resveratrol (3,5,4'-trihydroxy
      trans-stilbene; RES) on growth, cell cycle, and cyclins A, E, and B1 expression
      was investigated in the human SK-Mel-28 melanoma cell line. In addition, the
      structurally related compounds 4-hydroxy-trans-stilbene (4HST), piceatannol
      (3,5,3',4'-tetrahydroxy-trans-stilbene (PICE), and 4-trans-stilbenemethanol
      (4STMe) were also assayed in order to investigate the requirements of stilbenes
      to exert activity against melanoma cells. Both RES and 4HST inhibited cell growth
      in a dose- and time-dependent manner and upregulated the expression of cyclins A,
      E, and B1 with subsequent irreversible arrest of melanoma cells in the S-phase,
      concomitant with a decrease in G0/G1 and G2/M phases. In addition, potent
      apoptosis-mediated cell death was detected with the annexin V assay whereas no
      apoptosis was observed by flow cytometry, which encourages the assay of different
      methodologies to evaluate the effect of polyphenols on cell lines. The effect of
      PICE was not evaluated because of its instability in the reaction medium. No
      effect on cell cycle and cyclins expression was observed when 4STMe was assayed,
      which supported the critical requirement of the 4'-hydroxystyryl moiety to exert
      the above effects. In addition, this structural requirement also influenced the
      cellular uptake of stilbenes. The presence of two extra hydroxyl groups in RES
      increased its cytotoxicity whereas it diminished its efficiency to inhibit cell
      growth, upregulate cyclins expression, and arrest cell cycle in the S-phase with
      respect to 4HST. The present study suggests that the antimelanoma properties of
      dietary stilbenes, such as grape RES, cannot be ruled out, taking into account
      previous studies concerning the relationship between plasma and tissue
      concentrations and pharmacological activity of RES in animal models.

PMID- 14705881
TI  - Toxicity and repellency of patchouli oil and patchouli alcohol against Formosan
      subterranean termites Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae).
AB  - Patchouli oil obtained from Pogostemon cablin (Blanco) Benth and its main
      constituent, patchouli alcohol, were tested for their repellency and toxicity
      against Formosan subterranean termites (Coptotermes formosanus Shiraki). Both
      were found to be toxic and repellent. Unusual tissue destruction was noted inside
      the exoskeleton of the termite after patchouli alcohol was topically applied to
      the dorsum.

PMID- 14705882
TI  - Alkylperoxyl radical scavenging activity of red leaf lettuce (Lactuca sativa L.)
      phenolics.
AB  - Although lettuce may provide relatively low levels of antioxidative
      phytochemicals which may contribute to human health, lettuce leaf extracts in
      fact contained compounds with high specific peroxyl radical scavenging
      activities. After determining the extraction conditions that minimized phenolic
      oxidation and produced the highest oxygen radical absorbance capacity (ORAC)
      values, the phenolic compounds from red leaf lettuce were separated by reverse
      phase high-performance liquid chromatography (HPLC). The primary phenolic
      compounds in the leaf tissue extracts were mono- and dicaffeoyltartaric acid (CTA
      and DCTA), mono- and dicaffeoylquinic acid (CQA and DCQA), quercetin 3
      malonylglucoside (QMG), quercetin 3-glucoside (QG), cyanidin 3-malonylglucoside
      (CMG), and an unknown phenolic ester (UPE). Significant levels of DCQA were only
      found after wounding. Using the new fluorescein-based ORAC assay procedures,
      fractions from the HPLC analyses were assayed for peroxyl radical absorbance
      capacity. Using absorbance to estimate concentration, the decreasing order of
      contribution to the total ORAC value of an extract from wounded tissue was QMG >
      DCQA > CMG > DCTA > UPE > QG > CTA. The decreasing order of the specific peroxyl
      radical scavenging activities was CMG > QG > DCTA > DCQA > QMG > UPE > CQA > CTA.
      Since the concentrations of plant flavonoid and phenolic acid esters are
      sensitive to environmental factors, this information may be used to develop pre-
      and postharvest conditions which increase the dietary benefits of leaf lettuce.

PMID- 14705883
TI  - Synthesis of lipophilic clovamide derivatives and their antioxidative potential
      against lipid peroxidation.
AB  - Some N-(hydroxycinnamoyl)-L-tyrosine and L-DOPA alkyl esters were synthesized and
      evaluated as a variation of the clovamide (N-caffeoyl-L-3,4
      dihydroxyphenylalanine) structure, a known antioxidant found in red clover. The
      amides were prepared in good yields starting from methyl and dodecylesters of L
      tyrosine and L-DOPA by reacting with the N-hydroxysuccinimidyl esters of ferulic,
      sinapic, and acetyl-protected caffeic acid, respectively. In the DPPH* (2,2
      diphenyl-1-picrylhydrazyl) and superoxide radical quencher assays they showed
      radical scavenging activity equal to or higher than those of the standard
      antioxidants ascorbic acid and tocopherol. The antioxidative potentials of the
      clovamide derivatives against bulk lipid oxidation, as determined by the
      accelerated autoxidation of oils, were equal to or higher than those of the
      standard antioxidants; some of the compounds were able to protect an emulsion of
      linoleic acid/beta-carotene against oxidation. N-Caffeoyl L-tyrosine methyl ester
      and the N-cinnamoyl L-DOPA alkyl esters especially were potent antioxidants in
      bulk lipids and moderate protectants in emulsions.

PMID- 14705884
TI  - Stability and bioaccessibility of isoflavones from soy bread during in vitro
      digestion.
AB  - The impact of simulated digestion on the stability and bioaccessibility of
      isoflavonoids from soy bread was examined using simulated oral, gastric, and
      small intestinal digestion. The aqueous (bioaccessible) fraction was isolated
      from digesta by centrifugation, and samples were analyzed by high-performance
      liquid chromatography (HPLC). Isoflavonoids were stable during simulated
      digestion. Partitioning of aglycones, acetylgenistin, and malonylgenistin into
      the aqueous fraction was significantly (P < 0.01) affected by the concentration
      of bile present during small intestinal digestion. Omission of bile resulted in
      nondetectable genistein and <40% of total daidzein, glycitein, and acetylgenistin
      in the aqueous fraction of digesta. Partitioning of these compounds into the
      aqueous fraction was increased by physiological concentrations of bile extract.
      These results suggest that micellarization is required for optimal
      bioaccessibility of isoflavonoid aglycones. We propose that the bioavailability
      of isoflavones from foods containing fat and protein may exceed that of
      supplements due to enhanced bile secretion.

PMID- 14705885
TI  - Phytotoxic effects of wheat extracts on a herbicide-resistant biotype of annual
      ryegrass (Lolium rigidum).
AB  - Thirty-nine wheat accessions were used to evaluate their extract phytotoxicity
      against annual ryegrass (Lolium rigidum Gaud.). Aqueous extracts of wheat shoot
      residues significantly inhibited the germination and root growth of a biotype of
      annual ryegrass resistant to herbicides of acetyl CoA carboxylase inhibitors
      (group A), acetolactate synthase inhibitors (B), photosystem II inhibitors (C),
      and tubulin formation inhibitors (D). The germination of the herbicide resistant
      (HR) biotype was inhibited by 3-100%, depending upon the wheat accession. The
      phytotoxic effects on ryegrass root growth ranged from 12% stimulation to 100%
      inhibition, compared to a control. The germination and root growth of a herbicide
      susceptible (HS) biotype of annual ryegrass were also inhibited by the wheat
      extracts, with germination inhibited by 4-100%, and root growth by 19-100%.
      Bioassays with two known wheat allelochemicals showed that p-coumaric acid and
      propionic acid significantly inhibited the growth of both HR and HS biotypes of
      annual ryegrass. The two compounds completely inhibited the root growth of HR
      ryegrass at concentrations greater than 5.0 mM. In comparison with p-coumaric
      acid, propionic acid was more inhibitory to seed germination, shoot, and root
      growth of both ryegrass biotypes. The root growth of the HR biotype was more
      sensitive when exposed to wheat extracts, to p-coumaric acid, and to propionic
      acid. The results suggest that residues of certain wheat cultivars with strong
      allelopathic potential could provide a nonherbicidal alternative for the
      management of herbicide-resistant weed species.

PMID- 14705886
TI  - Chemical assessment of roots of Panax notoginseng in China: regional and seasonal
      variations in its active constituents.
AB  - Root of Panax notoginseng (Radix Notoginseng, Sanqi) is a well-known traditional
      Chinese medicine and is mainly cultivated in Wenshan of Yunnan, China. The active
      constituents include saponin, dencichine, flavonoid, and polysaccharide; however,
      the levels of these components vary in different geographical regions of growth
      and also show a seasonal variation. By using high-performance liquid
      chromatography and spectrophotometry, the contents of notoginsenoside R1,
      ginsenoside R(g1), R(b1), R(d), dencichine, flavonoid, and polysaccharide were
      determined and compared with Radix Notoginseng collected from different regions
      of growth in China, as well as from different seasons of harvest and market
      grades. Using the contents of these active constituents as markers, the best
      quality of Radix Notoginseng is found in the southwestern parts of Wenshan, and
      the best season for the harvest is September to October. In addition, the
      unseeded plants produced a better quality of Radix Notoginseng. The current
      results provide useful information for the quality control of Radix Notoginseng
      and its further development in establishing the good agriculture practice
      standard of P. notoginseng in China.

PMID- 14705887
TI  - Free radical scavenging activity of chitooligosaccharides by electron spin
      resonance spectrometry.
AB  - The radical scavenging effects of chitooligosaccharides (COSs) on hydroxyl
      radical, superoxide radical, alkyl radical, and 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical were investigated using a spin-trapping electron spin resonance
      (ESR) method and compared with the ESR signal intensity. COSs exhibited strong
      scavenging activity on hydroxyl radical and superoxide radical and weak
      scavenging activity on alkyl radical and DPPH radical. The radical scavenging
      activity of COSs increased with increment of concentration, and it was also
      dependent on molecular weight. These results suggest that the scavenging activity
      of COSs is dependent on their molecular weights and tested radicals.

PMID- 14705888
TI  - Production of saturated acyl L-ascorbate by immobilized lipase using a continuous
      stirred tank reactor.
AB  - 6-O-decanoyl, 6-O-dodecanoyl, or 6-O-tetradecanoyl L-ascorbate was continuously
      produced at 50 degrees C using a continuous stirred tank reactor (CSTR) with an
      immobilized lipase, Chirazyme L-2 C2, from Candida antarctica. Acetone was used
      as the reaction medium. For each saturated acyl L-ascorbate, the productivity of
      ca. 60 g/L reactor/day was achieved for at least 11 days. The solubility of the
      saturated acyl L-ascorbate in the soybean oil or water was measured at various
      temperatures. The solubilities in both the soybean oil and the water were higher
      for L-ascorbate with a shorter acyl chain. The acyl chain dependence of the
      solubility in water was stronger than that of the solubility in soybean oil. The
      temperature dependences of the solubility in both soybean oil and water could be
      expressed by the van't Hoff equation, and the dissolution enthalpy (DeltaH)
      values for the soybean oil and water were about 20 and 90 kJ/mol, respectively,
      irrespective of the acyl chain length. The radical scavenging activities of L
      ascorbic acid and the saturated acyl L-ascorbates against 1,1-diphenyl-2
      picrylhydrazyl free radical were ca. 95% for all of the compounds, and the
      introduction of a saturated acyl group to the L-ascorbic acid did not affect the
      activity.

PMID- 14705889
TI  - Crystal structures and structural stabilities of the disulfide bond-deficient
      soybean proglycinin mutants C12G and C88S.
AB  - The constituent subunits of seed storage protein 11S globulin have two disulfide
      bonds that are common among 11S globulins from legume and nonlegume seeds. In the
      case of the A1aB1b subunit of soybean 11S globulin, glycinin, Cys12-Cys45 and
      Cys88-Cys298 are observed by X-ray crystallography. The significance of these two
      disulfide bonds for structural stability was investigated by mutagenesis of Cys12
      to Gly and of Cys88 to Ser. The disulfide bond-deficient mutants C12G and C88S
      could form the correct conformations identical to that of the wild-type
      proglycinin except in the vicinities of the mutation sites C12 and C88 as shown
      by their crystal structures. Thermal stability monitored by differential scanning
      calorimetry of the mutants indicated that the contribution of these disulfide
      bonds to the thermal stability of proglycinin A1aB1b is low, although there is a
      small difference in the extent of the contribution between the two disulfide
      bonds (Cys12-Cys45 > Cys88-Cys298). The contribution of Cys88-Cys298 to the
      resistance of proglycinin A1aB1b to proteinase digestion is higher than that of
      Cys12-Cys45. Possible effects of structure on the different properties of C12G
      and C88S are discussed.

PMID- 14705890
TI  - Quantitation of Bt-176 maize genomic sequences by surface plasmon resonance-based
      biospecific interaction analysis of multiplex polymerase chain reaction (PCR).
AB  - Surface plasmon resonance (SPR) based biosensors have been described for the
      identification of genetically modified organisms (GMO) by biospecific interaction
      analysis (BIA). This paper describes the design and testing of an SPR-based BIA
      protocol for quantitative determinations of GMOs. Biotinylated multiplex
      Polymerase Chain Reaction (PCR) products from nontransgenic maize as well as
      maize powders containing 0.5 and 2% genetically modified Bt-176 sequences were
      immobilized on different flow cells of a sensor chip. After immobilization,
      different oligonucleotide probes recognizing maize zein and Bt-176 sequences were
      injected. The results obtained were compared with Southern blot analysis and with
      quantitative real-time PCR assays. It was demonstrated that sequential injections
      of Bt-176 and zein probes to sensor chip flow cells containing multiplex PCR
      products allow discrimination between PCR performed using maize genomic DNA
      containing 0.5% Bt-176 sequences and that performed using maize genomic DNA
      containing 2% Bt-176 sequences. The efficiency of SPR-based BIA in discriminating
      material containing different amounts of Bt-176 maize is comparable to real-time
      quantitative PCR and much more reliable than Southern blotting, which in the past
      has been used for semiquantitative purposes. Furthermore, the approach allows the
      BIA assay to be repeated several times on the same multiplex PCR product
      immobilized on the sensor chip, after washing and regeneration of the flow cell.
      Finally, it is emphasized that the presented strategy to quantify GMOs could be
      proposed for all of the SPR-based, commercially available biosensors. Some of
      these optical SPR-based biosensors use, instead of flow-based sensor chips,
      stirred microcuvettes, reducing the costs of the experimentation.

PMID- 14705891
TI  - Fate of oxidized triglycerides during refining of seed oils.
AB  - The evolution of oxidized triglycerides (ox-TG) during industrial refining was
      studied in soybean, sunflower, peanut, and corn oils. The analytical techniques
      used were silica gel column chromatography and high-performance size exclusion
      chromatography. The decrease in ox-TG during refining (42.3% on average) was
      accompanied by an increase in triglyceride oligopolymers (TGP). The inverse
      correlation between the two lipid groups suggests that the decrease in ox-TG
      during refining was due in part to the occurrence of polymerization reactions. An
      inverse correlation was also found between the percentage sum of ox-TG + TGP and
      percent TGP, indicating that a part of the ox-TG also underwent degradation or
      transformation reactions. On average, almost 58% of the ox-TG remained unchanged
      during refining and, of the rest, about half was involved in polymerization
      reactions and half in degradation or transformation reactions.

PMID- 14705892
TI  - Formation of soluble and micelle-bound protein aggregates in heated milk.
AB  - The formation of heat-induced aggregates of kappa-casein and denatured whey
      proteins was investigated in milk-based dairy mixtures containing casein micelles
      and serum proteins in different ratios. Both soluble and micelle-bound aggregates
      were isolated from the mixtures heated at 95 degrees C for 10 min, using size
      exclusion chromatography. Quantitative analysis of the protein composition of the
      aggregates by reverse phase high-performance liquid chromatography strongly
      suggested that primary aggregates of beta-lactoglobulin and alpha-lactalbumin in
      a 3 to 1 ratio were involved as well as kappa-casein, and alpha(s2)-casein in
      micellar aggregates. The results gave evidence that heat-induced dissociation of
      micellar kappa-casein was implicated in the formation of the soluble aggregates
      and indicated that a significant amount of kappa-casein was left unreacted after
      heating. The average size of the aggregates was 3.5-5.5 million Da, depending on
      the available kappa-casein or the casein:whey protein ratio in the mixtures. The
      size and density of these aggregates relative to those of casein micelles were
      discussed.

PMID- 14705893
TI  - Comparative methyl linoleate and methyl linolenate oxidation in the presence of
      bovine serum albumin at several lipid/protein ratios.
AB  - The oxidation of methyl linoleate (LMe) and methyl linolenate (LnMe) in the
      presence of bovine serum albumin (BSA) in the dark at 60 degrees C was studied to
      analyze the role of the type of fatty acid and the protein/lipid ratio on the
      relative progression of the processes involved when lipid oxidation occurs in the
      presence of proteins. The disappearance of the fatty acid, the formation of
      primary and secondary products of lipid peroxidation, the loss of amino acid
      residues, the production of oxidized lipid/amino acid reaction products, and the
      development of color and fluorescence were studied as a function of incubation
      time in protein/lipid samples at 10:1, 6:1, and 3:1 w/w ratios. The incubation of
      LMe and LnMe in the presence of BSA at 60 degrees C rapidly produced lipid
      peroxidation and protein damage. Although reaction rates were much faster for
      LnMe than for LMe, both fatty acids had similar behaviors, and LnMe seemed to be
      only slightly more reactive than LMe for BSA by producing a higher increase of
      protein pyrroles in the protein and the development of increased browning and
      fluorescence. The protein/lipid ratio also influenced the relative progress of
      the reactions implicated. Thus, a lower protein/lipid ratio increased sample
      oxidation and protein damage. This also produced an increased browning, in
      accordance with the mechanisms proposed for browning production by oxidized
      lipid/protein reactions. On the contrary, browning of extracted lipids increased
      at higher protein/lipid ratios. This opposite tendency allowed evaluation of the
      overall significance of the different browning processes implicated in the final
      colors observed, concluding that color changes observed in BSA/lipid samples were
      mostly a consequence of oxidized lipid/protein reactions.

PMID- 14705894
TI  - Relationship between potentiometric measurements, sensorial analysis, and some
      substances responsible for aroma degradation of white wines.
AB  - Oxidative degradation of white wines can be described sensorially as developing
      from a loss at positive aroma characteristics, through the development of
      negative aromas to a linel stage of chromatic alterations. This work attempts to
      relate the oxidation "status" evaluate by potentiometric titrations, with
      sensorial degradation and the levels of substances responsible for "off-flavors",
      such as methional and phenylacetaldehyde. The potentiometric titration employed
      measures the most powerful antioxidants of white wines (e.g., those which more
      rapidly consume oxygen). Considering that aromatic precedes chromatic
      degradation, resistance to oxidation (ROX) constitutes a useful indicator of
      resistance to oxidation. Sensorial degradation (ID), potentiometric measures, and
      volatiles were determined both in samples submitted to a "forced aging" protocol
      and normal aged white wines. High correlation values were observed between ROX
      and the ID, in both sets (r > 0.87). ID is better explained by ROX values than by
      the indicated wine age or by the "degree of browning" (Abs = 420 nm). It was also
      observed that in samples with ROX values higher than 10, the concentration of
      methional and phenylacetaldehyde were above their respective odor threshold.
      Finally, it was observed that there is a relationship between oxygen consumption
      and the respective ROX. Although these results seem very promising, they needed
      to be further complemented in order to estimate the shelf life of a white wine
      using potentiometric titrations.

PMID- 14705895
TI  - Effect of pentosanase and oxidases on the characteristics of doughs and the
      glutenin macropolymer (GMP).
AB  - Rheological characteristics of dough and glutenin macropolymer (GMP) extracted
      thereof were investigated. Three single enzymes, pentosanase (PP), glucoseoxidase
      (GLZ), and laccase (LAC), and their combinations were used. GLZ gave the least
      extensible and most resistant dough, and pentosanase/glucoseoxidase (PPGLZ)
      resulted in dough with improved extensibility. The enzymes improved gluten
      quality. The glutenin macropolymer (GMP) was characterized in terms of wet
      weight, protein content, pentosan association, and dynamic rheological
      properties. Enzymatic addition decreased the wet weight of GMP but increased the
      protein content. PP decreased the content of pentosans on the GMP, but single
      oxidases increased the content of pentosans associated with GMP. PP did not
      modify the elastic modulus (G') of the GMP, whereas GLZ increased G' by
      increasing the polymerization of proteins and LAC diminished G'. The combination
      PPGLZ produced a synergic increase of G'.

PMID- 14705896
TI  - 1-methylcyclopropene increases storability and shelf life in climacteric and
      nonclimacteric plums.
AB  - The effect of 1-methylcyclopropene (1-MCP) at three different doses (0.25, 0.50,
      and 0.75 microL L(-1)) on the ripening processes of a climacteric, cv. Santa
      Rosa, and a suppressed climacteric type, cv. Golden Japan, plum was studied. For
      both cultivars, positive effects were observed in terms of inhibition of ethylene
      production and delays of the physical, chemical, and biochemical changes
      associated with ripening. 1-MCP-treated plums were firmer with lower weight loss,
      reduced degrees Brix/titratable acidity ratios, and lower color changes during
      cold storage and subsequent shelf life at 20 degrees C than controls. For most
      factors, the effectiveness of 1-MCP was dose-dependent in Santa Rosa but dose
      independent for Golden Japan.

PMID- 14705897
TI  - Phytate phosphorus hydrolysis as influenced by dietary calcium and micro-mineral
      source in broiler diets.
AB  - Phytate phosphorus (PP) hydrolysis by a 3-phytase was studied in vitro at pH 2.5
      and 6.5 with either 0, 1.0, 4.0, or 9.0 g of Ca/kg diet, or 0, 1.0, 5.0, 7.5, or
      10.0 g/kg diet of micro-mineral premix added as inorganic (IMM) or an equivalent
      level as micro-mineral-amino acid complexes (MAAC). Adding Ca or micro-minerals
      reduced (P < 0.05) PP hydrolysis at both pHs; however, the effect was greater at
      pH 6.5. An in vivo experiment was conducted in which broilers were fed one of six
      diets for 30 h. The experimental design was a factorial of three micro-mineral
      forms (0 added, IMM, and MAAC) and two Ca levels (0 or 5 g/kg). Adding Ca reduced
      (P < 0.05) PP disappearance and increased Ca apparent absorption. No micro
      minerals effect (P > 0.05) was seen. Therefore, in poultry diets, it is Ca that
      inhibits PP hydrolysis and decreases P availability.

PMID- 14705898
TI  - Changes during storage in conventional and ecological wine: phenolic content and
      antioxidant activity.
AB  - Polyphenol content, free radical scavenging capacity, and changes during storage
      over 7 months in the dark were studied in ecological and conventional red and
      white wines. In red wines, the most changeable components during storage were the
      anthocyanins since during storage anthocyanins content decreased 88% in
      conventional wine and 91% in ecological wine. Initially, the total flavonol
      contents of the conventional and ecological red wines were 163.88 +/- 2.69 and
      153.58 +/- 1.71 mg/L, respectively, and no significant variations occurred during
      storage. No differences in hydroxycinnamic acid derivatives content between
      conventional and ecological red and white wines were observed. The flavonol level
      in white wines was very low, as expected since these compounds are found in grape
      skin. The initial antioxidant activity was 5.37 +/- 0.14 and 5.82 +/- 0.31 mM
      equivalents Trolox for conventional and ecological red wines, respectively; no
      significant differences were observed (p = 0.2831), and these values were 7-8
      times higher than the antioxidant activity observed in conventional and
      ecological white wine. In contrast with other studies, the total concentrations
      of phenolic compounds in conventional and ecological red and white wines were not
      related to antioxidant activity (p > 0.05). In red wines, no significant
      differences were observed in the antioxidant activity of ecological and
      conventional red wine (p = 0.28), while in white wine significant differences
      were observed in the antioxidant activity between conventional and ecological
      white wine (p = 0.006).

PMID- 14705899
TI  - Residue depletion study and withdrawal period for flunixin-N-methyl glucamine in
      bovine milk following intravenous administration.
AB  - The objective of this study was to establish a withdrawal period for flunixin in
      milk by quantifying 5-hydroxyflunixin, the marker residue, in bovine milk as a
      function of time, following intravenous treatment of lactating dairy cows with
      flunixin-N-methyl glucamine (Banamine or Finadyne). Lactating dairy cows were
      dosed on three consecutive days at 2.2 mg of flunixin free acid/kg of body
      weight/day. Milk was collected twice daily and assayed using a liquid
      chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The
      method was validated at concentrations in the range 0.5-250 ppb. The
      concentrations for 5-hydroxyflunixin measured 12 h after the last administration
      of drug ranged from 1.56 to 40.6 ppb for all cows. Milk concentrations for 5
      hydroxyflunixin were used to establish withdrawal periods of 36 h using
      guidelines established by the U.S. Food and Drug Administration/Center for
      Veterinary Medicine and 24 h using guidelines established by the European
      Medicinal Evaluation Agency/Committee on Veterinary Medicinal Products.

PMID- 14705900
TI  - Dissipation rates of cyprodinil and fludioxonil in lettuce and table grape in the
      field and under cold storage conditions.
AB  - Two fungicides (cyprodinil and fludioxonil) have recently been used in southeast
      Spain to control disease in lettuce and grape. Gas chromatography with a nitrogen
      phosphorus detector (GC-NPD) was used to study the disappearance of these
      compounds from crops under field conditions and during refrigeration. Residual
      values 21 days after application were below the maximum residue limit (MRL = 0.05
      mg kg(-1)) established by Spanish law in the field experiment for both compounds.
      However, with the exception of fludioxonil in lettuce, residues were above the
      MRL in the refrigerated farm produce for both fungicides. The half-lives were 3-6
      times greater under refrigeration.

PMID- 14705901
TI  - Uptake and metabolic fate of [14C]-2,4-dichlorophenol and [14C]-2,4
      dichloroaniline in wheat (Triticum aestivum) and soybean (Glycine max).
AB  - The uptake and metabolism of [14C]-2,4-dichlorophenol (DCP) and [14C]-2,4
      dichloroaniline (DCA) were investigated in wheat and soybean. Seeds were exposed
      to a nutrient solution containing 50 microM of one of two radiolabeled compounds,
      and plant organs were harvested separately after 18 days of growth. In wheat,
      uptake of [14C]-2,4-DCP was 16.67 +/- 2.65 and 15.50 +/- 2.60% of [14C]-2,4-DCA.
      In soybean, uptake of [14C]-2,4-DCP was significantly higher than [14C]-2,4-DCA
      uptake, 38.39 +/- 2.56 and 18.98 +/- 1.64%, respectively. In the case of [14C]
      2,4-DCP, the radioactivity absorbed by both species was found mainly associated
      with roots, whereas [14C]-2,4-DCA and related metabolites were associated with
      aerial parts, especially in soybean. In wheat, nonextractable residues
      represented 7.8 and 8.7% of the applied radioactivity in the case of [14C]-2,4
      DCP and [14C]-2,4-DCA, respectively. In soybean, nonextractable residues amounted
      to 11.8 and 5.8% of the total radioactivity for [14C]-2,4-DCP and [14C]-2,4-DCA,
      respectively. In wheat, nonextractable residues were nearly equivalent to
      extractable residues for [14C]-2,4-DCP, whereas they were greater for [14C]-2,4
      DCA. In soybean, the amount of extractable residues was significantly greater for
      both chemicals. However, in both species, nonextractable residues were mainly
      associated with roots. Isolation of soluble residues was next undertaken using
      excised shoots (wheat) or excised fully expanded leaves including petioles
      (soybean). Identification of metabolite structures was made by comparison with
      authentic standards, by enzymatic hydrolyses, and by electrospray ionization-mass
      spectrometric analyses. Both plant species shared a common metabolism for [14C]
      2,4-DCP and [14C]-2,4-DCA since the malonylated glucoside conjugates were found
      as the final major metabolites.

PMID- 14705902
TI  - Flumioxazin soil persistence and mineralization in laboratory experiments.
AB  - Flumioxazin is an herbicide registered for use in soybean and peanut. However,
      few published papers concerning the soil persistence of flumioxazin are
      available. Therefore, laboratory studies were initiated to determine the half
      life (t(1/2)) of flumioxazin in Greenville sandy clay loam and Tifton loamy sand
      soils when incubated at 15 and 25 degrees C. Results indicated that temperature
      had little effect on flumioxazin persistence. The t(1/2) for the Greenville soil
      was 17.9 and 16.0 days while the Tifton soil was 13.6 and 12.9 days, at 15 and 25
      degrees C, respectively. These data correspond to the greater clay content of the
      Greenville soil (32%) as compared to the Tifton soil (2%). Therefore, the
      Greenville soil had greater soil adsorption and less flumioxazin was generally
      available to be degraded by soil microorganisms. In soils that were heat treated
      to reduce microbe populations, 99% of initial flumioxazin was accounted for after
      16 days. Mineralization of flumioxazin, measured as 14CO2 evolution, was also
      greater in the Tifton soil (2.2% after 64 days) than in the Greenville soil (2.0%
      after 64 days). From these data, it was concluded that microbes were the most
      influential factor concerning the degradation of flumioxazin.

PMID- 14705903
TI  - Comparison of linear and nonlinear regression for modeling the first-order
      degradation of pest-control substances in soil.
AB  - First-order kinetic models are often used to profile the degradation of pest
      control compounds in soil. This approach is based on enzyme theory and is often
      favored due to its simplicity and its requirement by regulatory agencies. Here,
      linear and nonlinear regression approaches to modeling first-order decay are
      compared. Composite residual plots of many soil degradation data sets are
      presented on a normalized scale. These plots illustrate the general error
      structure for the data and are useful for detecting common mis-specifications of
      the models. Results indicate that a nonlinear regression approach to modeling
      first-order decay of compounds in soil more accurately describes most data sets
      when compared with a linear approach. Specifically, the observed error structure
      does not support the broad use of a logarithmic transformation to stabilize the
      variance. In addition, models generated using the linear approach generally
      exhibit more dramatic systematic deviations from the observations as compared
      with models generated using the nonlinear approach. The analysis methods
      described here may be useful for comparing alternative models in this and other
      research areas.

PMID- 14705904
TI  - Monitoring of feeds selenium status in a southeast region of Romania.
AB  - One hundred and eighty-five samples of feeds (hays, green plants, and concentrate
      feed) from households covering 41 localities in Dobrudja, a southeast region of
      Romania, were collected and analyzed for selenium (Se) content by
      spectrofluorometry with 2,3-diaminonaphthalene. Only 6.5% of the samples analyzed
      were, in terms of the feed Se content, considered appropriate (i.e., 0.15-0.30
      ppm), within the normal range. The remaining 93.5% proved to be Se deficient; the
      results fell into the 0.001-0.150 ppm range. Consequently, the samples were
      divided into three deficiency groups based on the content recorded as follows:
      severe for 3.2% (Se below 0.01 ppm), critical for 84.9% (Se in the 0.01-0.1 ppm
      range), and marginal for 5.4% (Se in the 0.1-0.15 ppm range). Conclusively, the
      Dobrudja feeds may be said to be generally Se deficient, which requires
      prophylactic and therapeutic measures to correct animal selenium deficiency.

PMID- 14705905
TI  - The influence of gel strength on aroma release from pectin gels in a model mouth
      and in vivo, monitored with proton-transfer-reaction mass spectrometry.
AB  - The course of events from taking a food into the mouth to the perception of the
      food's flavor involves many steps, from dilution with saliva, mastication, and
      transportation of the compounds to the olfactory epithelium to transformation
      into signals that go to the brain. In addition, there are also the effects of the
      food's structure and properties. In this study, a proton-transfer-reaction mass
      spectrometer (PTR-MS) was used to investigate how four pectin-containing systems
      with different structures and strengths affected the release of aroma compounds
      in a model mouth and in the nose of an assessor. Both the model mouth and the in
      nose measurements showed that the strength and structure of pectin-containing
      systems are important with regard to the quantity of aroma compounds that are
      released. Mastication and saliva were also shown to have a large influence on how
      much of the aroma compound is released from the mouth to the nose.

PMID- 14705906
TI  - Role of olive seed in the biogenesis of virgin olive oil aroma.
AB  - Results obtained in a set of experiments point to an effective participation of
      olive seeds in the biosynthesis of olive oil aroma through the lipoxygenase
      pathway during the extraction process to produce virgin olive oil. Data showed
      that olive seeds should contain enzymatic activities metabolizing 13
      hydroperoxides other than hydroperoxide lyase, giving rise to a net decrease in
      the content of C6 unsaturated aldehydes during the olive oil extraction process.
      Olive seeds seem also to supply this process with alcohol dehydrogenase activity,
      being more specific for saturated C6 aldehydes and not acting on C5 alcohols.
      Moreover, olive seeds would be responsible for the biosynthesis of 30-50% esters
      during the olive oil extraction process of intact fruits. Thus, olive seeds would
      afford a load of alcohol acyltransferase activity that might be quite unspecific
      in terms of substrate, producing any kind of esters.

PMID- 14705907
TI  - Effect of whey protein on the in vivo release of aldehydes.
AB  - Retention of aldehydes by whey proteins in solutions buffered at a range of pH
      values was studied under static and dynamic headspace conditions and in vivo in
      exhaled air. Static headspace measurements showed a clear increase in retention
      in the presence of whey proteins for aldehydes with longer carbon chains and for
      buffer solutions with higher pH values. For in vivo aldehyde release
      measurements, these effects were much less pronounced. The presence of saliva or
      the binding of aldehydes to the surface of the oral cavity was not responsible
      for this effect. This difference can be explained by the highly dynamic
      conditions of in vivo aroma release of liquid products, due to the relatively
      large flow of air during exhalation. After swallowing, a thin film of aldehyde
      solution remains in the pharynx; subsequent exhalation will release both the free
      aldehydes present in this film and those reversibly bound to the whey protein.

PMID- 14705908
TI  - 4-hydroxy-2,5-dimethyl-3(2H)-furanone formation by Zygosaccharomyces rouxii:
      effect of the medium.
AB  - The formation of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) by
      Zygosaccharomyces rouxii was studied in yeast-peptone-dextrose medium containing
      d-fructose 1,6-diphosphate under various culture conditions. Cell growth and HDMF
      production was heavily dependent on medium pH and sodium chloride concentration.
      Higher pH values of the nutrient medium had a positive effect on HDMF formation
      but retarded cell growth resulting in an optimal pH value of 5.1 with regard to
      the yield of HDMF. Salt stress stimulated HDMF formation by Z. rouxii as
      increasing sodium chloride concentration led to higher amounts of HDMF. The HDMF
      concentration in the culture supernatant and HDMF formation per yeast cell peaked
      at 20% sodium chloride in the nutrient medium. The nonutilizable carbohydrate d
      xylose displayed a weak effect on HDMF formation, and the addition of glycerol to
      salt-stressed cells had no effect on the production of HDMF.

PMID- 14705909
TI  - Ascorbic acid concentration in Cv. conference pears during fruit development and
      postharvest storage.
AB  - L-ascorbic acid (L-AA) concentration changes during the development of cv.
      Conference pears and the influence of postharvest handlings (gas condition,
      cooling rate, cooling duration) on L-AA breakdown were studied. L-AA
      concentration fluctuates in young fruits, remains stable during fruit maturation,
      and starts to decline 1 week before commercial harvest. The most rapid decrease
      in L-AA concentration was found during immediate controlled atmosphere. During
      short-term storage, only the gas condition was found to influence L-AA breakdown;
      no significant difference between gradually or immediately cooled pears was
      determined. Under air conditions, both cooling strategies did not differ from the
      L-AA breakdown in pears allowed to ripen on the tree up until 3 weeks after the
      optimal harvest date. During long-term storage, the cooling duration (1-3 weeks)
      had no effect whereas both O2 and CO2 had a significant effect on L-AA retention.
      After 7 months of storage, no difference was found in dehydroascorbic acid
      concentration; the L-AA and total L-AA concentrations, in contrast, were
      significantly lower in the 5% CO2 conditions.

PMID- 14705910
TI  - Application of microwave energy in the manufacture of enhanced-quality green tea.
AB  - Green tea manufacture was standardized with respect to the inactivation of
      polyphenol oxidase (PPO), rolling, and drying for quality manufacture.
      Inactivation of PPO by parching, steaming, microwave heating, and oven heating
      was monitored in tea shoots. The inactivated shoots were rolled under regimens of
      high and low pressures and dried by microwave heating, oven heating, or sun
      drying; total phenols and catechins were estimated. Parched and sun-dried teas
      contained the lowest levels of total phenols and catechins, and their infusions
      were dull in color with a slightly burnt odor. Microwave-inactivated and-dried
      teas showed the highest levels of total phenols and catechins, and their
      infusions were bright in color and sweet in taste with a subtle pleasant odor. In
      steam-inactivated and oven/microwave-dried teas, total phenol and catechin
      contents were intermediate between parched and sun-dried teas and microwave
      inactivated and microwave-dried teas, and their infusions were bright with a
      umami taste.

PMID- 14705911
TI  - Effect of proteolytic squid protein hydrolysate on the state of water and
      dehydration-induced denaturation of lizard fish myofibrillar protein.
AB  - With the goal of preparing low-cost functional food, squid protein hydrolysate
      (SPH) was extracted from four squid species by protease treatment. Peptides are
      the major components (approximately 84-88%) of the SPH. The stabilization effects
      of 5% SPH (dried weight/wet weight) on the state of water and the denaturation of
      frozen lizard fish Saurida wanieso myofibrillar protein (Mf) were evaluated on
      the basis of desorption isotherm curves with respect to Ca2+-ATPase inactivation
      and the presence of unfrozen water, which was determined using differential
      scanning calorimetry during dehydration, and the effects were compared with those
      of sodium glutamate. The Mf with SPH was found to contain higher levels of
      monolayer and multilayer sorption water, resulting in decreased water activity
      and Ca2+-ATPase inactivation. The amount of unfrozen water in Mf with SPH
      increased significantly, suggesting that the peptides of SPH stabilized water
      molecules on the hydration sphere of Mf, which maintained the structural
      stability of Mf, and therefore suppressed dehydration-induced denaturation. The
      effect by SPH was less than that by sodium glutamate.

PMID- 14705912
TI  - Solubilization patterns of lutein and lutein esters in food grade nonionic
      microemulsions.
AB  - Lutein, a naturally occurring carotenoid, is widely distributed in fruits and
      vegetables and is particularly concentrated in the Tagetes erecta flower.
      Epidemiological studies suggest that a high lutein intake (6 mg/day) increases
      serum levels that are associated with a lower risk of cataract and age-related
      macular degeneration. Lutein can either be free or esterified (myristate,
      palmitate, or stearate). Both are practically insoluble in aqueous systems, and
      their solubility in food grade solvents (oils) is very limited, resulting is low
      bioavailability. To improve its solubility and bioavailability, lutein was
      solubilized in U-type food grade microemulsions based on ethoxylated sorbitan
      fatty acid esters, glycerol, R-(+)-limonene, and ethanol. Some of the main
      findings are as follows: (1) reverse micellar and W/O compositions solubilized
      both luteins better than an O/W microemulsion, and maximum solubilization is
      obtained within the bicontinuous phase; (2) free lutein is solubilized better
      than the esterified one, in the W/O microemulsions, whereas the esterified lutein
      is better accommodated within the O/W microemulsion; (3) vegetable oils decrease
      the solubilization of free lutein; (4) glycerol and alcohol enhance the
      solubilization of both luteins; (5) solubilization is surfactant-dependent in all
      mesophase structures, but its strongest effect is in the bicontinuous phase.

PMID- 14705913
TI  - Acrylamide formation mechanism in heated foods.
AB  - Recent findings of a potential human carcinogen, acrylamide, in foods have
      focused research on the possible mechanisms of formation. We present a mechanism
      for the formation of acrylamide from the reaction of the amino acid asparagine
      and a carbonyl-containing compound at typical cooking temperatures. The mechanism
      involves formation of a Schiff base followed by decarboxylation and elimination
      of either ammonia or a substituted imine under heat to yield acrylamide. Isotope
      substitution studies and mass spectrometric analysis of heated model systems
      confirm the presence of key reaction intermediates. Further confirmation of this
      mechanism is accomplished through selective removal of asparagine with
      asparaginase that results in a reduced level of acrylamide in a selected heated
      food.

PMID- 14705914
TI  - Multielement composition of wines and their precursors including provenance soil
      and their potentialities as fingerprints of wine origin.
AB  - The influence of the provenance soil and vinification process on the wine
      multielemental composition was investigated. For this purpose, two different
      vineyards from the Douro wine district, Portugal, were selected. Monovarietal
      grapes from a 10 year old vineyard were used to produce a red table wine, in a
      very modern winery. Polyvarietal grapes from a 60-70 year old vineyard were used
      to produce a red fortified wine, similar to Port, through a traditional
      vinification process. The multielement compositions (Al, As, B, Ba, Be, Ca, Cd,
      Co, Cr, Cs, Cu, Fe, Ga, Hf, Li, Mn, Mo, Nb, Ni, Pb, Rb, Sb, Sc, Sr, Ti, Th, Tl,
      U, V, W, Y, Zn, Zr, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu)
      of soil, grape juices (prepared in the laboratory), and samples collected in the
      different steps of each winemaking process were measured. Inductively coupled
      plasma mass spectrometry was used, after suitable pretreatment of the samples (by
      UV irradiation for liquid samples and high-pressure microwave digestion for
      soil). Both vinification processes influenced the multielement composition of the
      wines. Most of the elements presented similar or even lower concentrations in the
      wine as compared to that observed in the respective grape juice, probably as a
      result of precipitation or coprecipitation with suspended particles during
      fermentation and/or wine aging. Evidence of effective contamination during grape
      pressing, fermentation, and/or fining of wines (depending on the element) was
      observed for Cd, Cr, Cu, Fe, Ni, Pb, V, and Zn in the fortified wine and Al, Cr,
      Fe, Ni, Pb, and V in the table wine. Nevertheless, significant correlations were
      obtained between the multielement composition of the wine and the respective
      grape juice (R = 0.997 and 0.979 for the fortified and table wines, respectively,
      n = 31, P < 0.01), as well as between that in the wine (median of the two studied
      wines) and the provenance soil (R = 0.994, n = 19, P < 0.01), for the set of
      elements determined in common in the different types of samples. These results
      are promising concerning the usefulness of the elemental patterns of both soil
      and wine as fingerprints of the origin of the studied wines. Nevertheless, more
      wines from the same and other wine districts must be studied in order to
      consolidate this conclusion. The multielement compositions of the studied wines
      were compared with those of wines of different characteristics and origins, as
      well as with the respective legal threshold limit values, when available.
      Relatively low metal levels, below their threshold limit values, were found in
      all cases.

PMID- 14705915
TI  - Bound malondialdehyde in foods: bioavailability of N,N'-di-(4-methyl-1,4
      dihydropyridine-3,5-dicarbaldehyde)lysine.
AB  - Reactions between lipid peroxidation products and proteins in foods have
      detrimental nutritional effects, most importantly, losses of essential amino
      acids. One of the major products of the reaction of malondialdehyde and alkanals
      with amino groups are 4-substituted 1,4-dihydropyridine-3,5-dicarbaldehyde
      derivatives. The product of the reaction of lysine with malondialdehyde and
      acetaldehyde, N,N'-di-(4-methyl-1,4-dihydropyridine-3,5-dicarbaldehyde)lysine
      (MDDL), has been synthesized and used for in vitro and in vivo bioavailability
      studies. Release of free lysine did not occur in incubations of MDDL with tissue
      homogenates. After oral administration of radioactively labeled MDDL,
      radioactivity was only recovered in feces. Radioactivity was not incorporated
      into hepatic microsomes after intraperitoneal administration, which would have
      indicated release of available lysine. These results show that MDDL is a form of
      unavailable lysine, because it is not metabolized to free lysine and cannot be
      absorbed from the gut. Thus, formation of this derivative in foods would result
      in loss of available lysine.

PMID- 14705916
TI  - Invertase inhibitors from sweet potato (Ipomoea batatas): purification and
      biochemical characterization.
AB  - Two proteinaceous invertase inhibitors, designated ITI-L and ITI-R, were purified
      to electrophoretic homogeneity. ITI-L was purified from acetone powder of sweet
      potato leaves through sequential steps entailing buffer extraction, acid
      treatment, DEAE-Sephacel ion-exchange chromatography, and Sephacryl S-100 gel
      filtration. ITI-R was purified from sweet potato tuberous roots by sequentially
      applying buffer extraction, Con A-Sepharose affinity chromatography, DEAE
      Sephacel ion-exchange chromatography, Sephacryl S-200, and Superose 12 gel
      filtration. The optimal pHs for interaction between ITI-L and ITI-R and acid
      invertase from sweet potato leaves were 5.5 and 5.0, respectively. The molecular
      masses of ITI-L and ITI-R were 10 and 22 kDa, respectively, as estimated by both
      gel filtration and SDS-PAGE. Both inhibitors were thermostable (90% of the
      activity remained after incubation at 100 degrees C for 20 min), and Western
      blotting showed them to be immunologically related.

PMID- 14705917
TI  - Spiro cross-links: representatives of a new class of glycoxidation products.
AB  - Covalently cross-linked proteins are among the major modifications caused by the
      advanced Maillard reaction. So far, the chemical nature of these aggregates is
      largely unknown. Investigations are reported on the isolation of 6-[2-[[(4S)-4
      amino-4-carboxybutyl]amino]-6,7-dihydroxy-6,7-dihydroimidazo[4,5-b]azepin-4(5H)
      yl]-L-norleucine (10) and N-acetyl-6-[(6R,7R)-2-[[4-(acetylamino)-4
      carboxybutyl]amino]-6,7,8a-trihydroxy-6,7,8,8a-tetrahydroimidazo[4,5-b]azepin
      4(5H)-yl]-L-norleucine (12) formed by oxidation of the major Maillard cross-link
      glucosepane 1. Independent synthesis and unequivocal structural characterization
      are given for 10 and 12. Spiro cross-links, representing a new class of
      glycoxidation products, were obtained by dehydrogenation of the amino
      imidazolinimine compounds N6-[2-[[(4S)-4-ammonio-5-oxido-5-oxopentyl]amino]-5
      [(2S,3R)-2,3,4-trihydroxybutyl]-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysinate
      (DOGDIC 2) and N6-[2-[[(4S)-4-ammonio-5-oxido-5-oxopentyl]amino]-5-[(2S)-2,3
      dihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysinate (DOPDIC 3). These
      new oxidation products were synthesized, and their unambiguous structural
      elucidation proved the formation of the spiro imidazolimine structures N6
      [(7R,8S)-2-[[(4S)-4-ammonio-5-oxido-5-oxopentyl]amino]-8-hydroxy-7
      (hydroxymethyl)-6-oxa-1,3-diazaspiro[4.4]non-1-en-4-ylidene]-L-lysinate (16), N6
      (8R,9S)-2-[(4S)-4-ammonio-5-oxido-5-oxopentyl]amino]-8,9-dihydroxy-6-oxa-1,3
      diazaspiro[4.5]dec-1-en-4-ylidene)-L-lysinate (19), and N6-[(8S)-2-[(4-amino-4
      carboxybutyl)amino]-8-hydroxy-6-oxa-1,3-diazaspiro[4.4]non-1-en-4-ylidene]-L
      lysinate (18), respectively. It was shown that reaction of the imidazolinone 15
      led to the formation of spiro imidazolones, structurally analogous to 16 and 19.

PMID- 14705918
TI  - Effect of gamma-irradiation on degradation of alginate.
AB  - The aqueous solution of alginate was irradiated by 60Co gamma-rays in the dose
      range of 10-500 kGy. To assess the effect of irradiation on the degradation of
      alginate, the irradiation-induced changes in the viscosity, molecular weight,
      color, monomer composition, and sequence were measured. The molecular weight of
      raw alginate was reduced from 300000 to 25000 when irradiated at 100 kGy. The
      degradation rate decreased and the chain breaks per molecule increased with
      increasing irradiation dose. The viscosity of irradiated alginate solution
      reached a near minimum as low as at 10 kGy. No appreciable color changes were
      observed in the samples irradiated at up to 100 kGy, but intense browning
      occurred beyond 200 kGy. The 13C NMR spectra showed that homopolymeric blocks, MM
      and GG, increased and the M/G ratio decreased with irradiation. Considering both
      the level of degradation and the color change of alginate, the optimum
      irradiation dose was found to be 100 kGy.

PMID- 14705919
TI  - Effect of red mold rice supplements on serum and egg yolk cholesterol levels of
      laying hens.
AB  - Monacolin K is a secondary metabolite of Monascus species and reduces cholesterol
      levels. This research focuses on the effect of adding red mold rice to hens' diet
      on cholesterol level in egg yolk and on cholesterol, triglyceride, high-density
      lipoprotein (HDL), and low-density lipoprotein (LDL) levels in serum. Forty-eight
      Hy-line laying hens of 48 weeks of age were studied by dividing them into four
      groups. Except for the control group, the feed for three other groups contained
      2.0, 5.0, and 8.0% red mold rice (monacolin K concentrations were 0.0145, 0.035,
      and 0.056%, respectively). The experiment lasted 6 weeks. During this period, egg
      weight and egg production were recorded every day, and cholesterol, triglyceride,
      HDL, and LDL in serum were measured weekly as well. The result showed that the
      cholesterol in eggs produced by experimental groups was lower than that of the
      control group (0%, 194.14 +/- 8.30; 2%, 167.17 +/- 4.34; 5%, 168.93 +/- 9.38; 8%,
      183.02 +/- 7.63 mg/egg; p < 0.05), and the triglyceride (0%, 1494 +/- 178; 2%,
      1280 +/- 174; 5%, 1189 +/- 248; 8%, 1381 +/- 218 mg/dL; p < 0.05) and LDL levels
      (0%, 36.81 +/- 5.53; 2%, 32.25 +/- 7.93; 5%, 30.06 +/- 4.39; 8%, 28.81 +/- 4.16
      mg/dL; p < 0.05) were also significantly lowered in the experimental groups.
      However, the HDL level did not show significant change for either control or
      experimental groups (0%, 36.06 +/- 3.96; 2%, 36.25 +/- 5.39; 5%, 33.13 +/- 3.68;
      8%, 31.44 +/- 4.29 mg/dL; p > 0.05). Besides, the addition of red mold rice also
      helps to inhibit production of malondialdehyde (MDA) in serum lipid oxidation
      (0%, 27.42 +/- 0.53; 2%, 25.62 +/- 0.76; 5%, 24.35 +/- 0.59; 8%, 23.63 +/- 0.48
      microM; p < 0.05).

PMID- 14705920
TI  - Detecting potential IgE-reactive sites on food proteins using a sequence and
      structure database, SDAP-food.
AB  - The high incidence of food allergies, including oral allergy syndrome, represent
      major considerations when introducing new crops and foods. A new structural
      database of allergenic proteins, SDAP-Food, http://fermi.utmb.edu/SDAP/, has been
      developed to aid in predicting the IgE-binding potential of novel food proteins
      and cross-reactivities among known allergens. The site is designed to facilitate
      the first steps of a decision tree approach to determine the allergenicity of a
      given protein, based on the sequence and structural similarity to known allergens
      and their IgE binding sites. Immunological tests can then be used to confirm the
      predictions. A hierarchical procedure for identifying potential allergens, using
      a physical property-based sequence similarity index, has been designed to
      identify regions that resemble known IgE binding sites. As an example, SDAP tools
      were used to find food allergen sequences similar to an IgE binding site of the
      Jun a 3 allergen from mountain cedar pollen. The SDAP sequence similarity search
      matched the Jun a 3 epitope to regions in several food allergens, including
      cherry (Pru av 2), apple (Mal d 2) and pepper (Cap a 1), which are, like Jun a 3,
      members of the plant pathogenesis-related (PR-5) protein family. Homology
      modeling, using our EXDIS/DIAMOD/FANTOM program suite, indicated a similar
      surface location and structure for the potential epitope region on all of these
      allergens. The quantitative approach presented here can be used as part of a
      screening process for potential allergenicity of recombinant food products.

PMID- 14705921
TI  - Gymnodimine C, an isomer of gymnodimine B, from Karenia selliformis.
AB  - Gymnodimine C (1), an oxidized analogue of the spiro-imine algal toxin
      gymnodimine (3), was isolated from extracts of the cells of Karenia selliformis.
      The structure of gymnodimine C, determined by one- and two-dimensional 1H NMR
      spectroscopy and mass spectrometry, was found to be isomeric with gymnodimine B
      (2) at C-18.

PMID- 14705922
TI  - Contamination of pastures by polycyclic aromatic hydrocarbons (PAHs) in the
      vicinity of a highway.
AB  - To assess PAH contamination pastures, grass and soil samples have been collected
      from 10 m (d1), 50 m (d2), and 150 m (d3) perpendicular to a French highway
      (70,000 vehicles per day) and at a control site in a rural area away from nearby
      contaminating sources. Total PAH concentration ranges from 767 ng/g dry weight to
      3989 ng/g dry weight, according to the matrix and the distance from the highway.
      Distance is not a significant factor for PAH deposition on grass, while in soil
      it has an effect between d1 and d2 or d3. The total PAH concentration in highway
      samples is 8 times higher than in control site samples for grass and 7 to 4 times
      higher for soil. Fluoranthene, pyrene, and phenanthrene are the major PAHs in
      grass samples at the control site and the highway, but the concentrations are
      about 5 times higher near the highway. In soil samples collected near the
      highway, the values of concentrations between all compounds are not statistically
      different. PAH deposition on grass is linked to the physicochemical properties of
      the compounds, which lead to a specific distribution of each molecule (according
      to their volatility and the number of aromatic rings) while no specific behavior
      is revealed in soil.

PMID- 14705925
TI  - Local-global conformational coupling in a heptahelical membrane protein:
      transport mechanism from crystal structures of the nine states in the
      bacteriorhodopsin photocycle.
AB  - Proton pumps utilize a chemical or photochemical reaction to create pH and
      electrical gradients between the interior and the exterior of cells and
      organelles that energize ATP synthesis and the accumulation and extrusion of
      solutes and ions. G-protein coupled receptors bind agonists and assume signaling
      states that communicate with the coupled transducers. How these two kinds of
      proteins convert chemical potential to a proton transmembrane electrochemical
      potential or a signal are the great questions in structural membrane biology, and
      they may have a common answer. Bacteriorhodopsin, a particularly simple integral
      membrane protein, functions as a proton pump but has a heptahelical structure
      like membrane receptors. Crystallographic structures are now available for all of
      the intermediates of the bacteriorhodopsin transport cycle, and they describe the
      proton translocation mechanism, step by step and in atomic detail. The results
      show how local conformational changes propagate upon the gradual relaxation of
      the initially twisted photoisomerized retinal toward the two membrane surfaces.
      Such local-global conformational coupling between the ligand-binding site and the
      distant regions of the protein may be the shared mechanism of ion pumps and G
      protein related receptors.

PMID- 14705926
TI  - Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine
      phosphorylase and X-ray structure with MT-immucillin-A.
AB  - Methythioadenosine phosphorylase (MTAP) functions solely in the polyamine pathway
      of mammals to remove the methylthioadenosine (MTA) product from both spermidine
      synthase (2.5.1.16) and spermine synthase (2.5.1.22). Inhibition of polyamine
      synthesis is a validated anticancer target. We designed and synthesized
      chemically stable analogues for the proposed transition state of human MTAP on
      the basis of the known ribooxacarbenium character at all reported N
      ribosyltransferase transition states [Schramm, V. L. (2003) Acc. Chem. Res. 36,
      588-596]. Methylthio-immucillin-A (MT-ImmA) is an iminoribitol tight-binding
      transition state analogue inhibitor with an equilibrium dissociation constant of
      1.0 nM. The immucillins resemble the ribooxacarbenium ion transition states of N
      ribosyltransferases and are tightly bound as the N4' cations. An ion pair formed
      between the iminoribitol cation and phosphate anion mimics the ribooxacarbenium
      cation-phosphate anion pair formed at the transition state and is confirmed in
      the crystal structure. The X-ray crystal structure of human MTAP with bound MT
      Imm-A also reveals that the 5'-methylthio group lies in a flexible hydrophobic
      pocket. Substitution of the 5'-methylthio group with a 5'-phenylthio group gives
      an equilibrium binding constant of 1.0 nM. Methylthio-DADMe-immucillin-A is a
      pyrrolidine analogue of the transition state with a methylene bridge between the
      9-deazaadenine group and the pyrrolidine ribooxacarbenium mimic. It is a slow
      onset inhibitor with a dissociation constant of 86 pM. Improved binding energy
      with DADMe-immucillin-A suggests that the transition state is more closely
      matched by increasing the distance between leaving group and ribooxacarbenium
      mimics, consistent with a more dissociative transition state. Increasing the
      hydrophobic volume near the 5'-position at the catalytic site with 5'-phenylthio
      DADMe-immucillin-A gave a dissociation constant of 172 pM, slightly weaker than
      the 5'-methylthio group. p-Cl-phenylthio-DADMe-immucillin-A binds with a
      dissociation constant of 10 pM (K(m)/K(i) value of 500000), the tightest binding
      inhibitor reported for MTAP. These slow-onset, tight-binding transition state
      analogue inhibitors are the most powerful reported for MTAP and have sufficient
      affinity to be useful in inhibiting the polyamine pathway.

PMID- 14705927
TI  - Destabilizing mutations promote membrane protein misfolding.
AB  - In this work, the relationship between stability and propensity to misfold was
      probed for a series of purified variants of the polytopic integral membrane
      protein diacylglycerol kinase. It was observed that there was a strong
      correlation between stability and folding efficiency. The most common mutations
      that promoted misfolding were those which also destabilized the protein. These
      results imply that by targeting unstable membrane proteins for degradation,
      cellular protein folding quality control can eliminate proteins that have a high
      intrinsic propensity to misfold into aberrant structures. Moreover, the more rare
      class of amino acid mutations that promote misfolding without perturbing
      stability may be particularly dangerous because the mutant proteins may evade the
      surveillance of cellular quality control systems.

PMID- 14705928
TI  - Solubilization and purification of the MotA/MotB complex of Escherichia coli.
AB  - Bacterial flagella are driven at their base by a rotary motor fueled by the
      membrane gradient of protons or sodium ions. The stator of the flagellar motor is
      formed from the membrane proteins MotA and MotB, which function together to
      conduct ions across the membrane and couple ion flow to rotation. An invariant
      aspartate residue in MotB (Asp32 in the protein of E. coli) is essential for
      rotation and appears to have a direct role in proton conduction. A recent study
      showed that changes at Asp32 in MotB cause a conformational change in the
      complex, as evidenced by altered patterns of protease susceptibility of MotA
      [Kojima, S., and Blair, D. F. (2001) Biochemistry 40 (43), 13041-13050]. It was
      proposed that protonation/deprotonation of Asp32 might regulate a conformational
      change in the stator that acts as the powerstroke to drive rotation of the rotor.
      Biochemical studies of the MotA/MotB complex have been hampered by the absence of
      a suitable assay for its integrity in detergent solution. Here, we have studied
      the behavior of the MotA/MotB complex in a variety of detergents, making use of
      the protease-susceptibility assay to monitor its integrity. Among about 25
      detergents tested, a few were found to solubilize the proteins effectively while
      preserving certain conformational properties characteristic of an intact complex.
      The detergent dodecylphosphocholine, or DPC, proved especially effective.
      MotA/MotB complexes purified in DPC migrate with an apparent size of
      approximately 300 kDa in gel-filtration columns, and retain the Asp32-modulated
      conformational differences seen in membranes. (35)S-radiolabeling showed that
      MotA and MotB are present in a 2:1 ratio in the complex. Purified MotA/MotB
      complexes should enable in vitro study of the proton-induced conformational
      change and other aspects of stator function.

PMID- 14705929
TI  - Arrangement of core membrane segments in the MotA/MotB proton-channel complex of
      Escherichia coli.
AB  - The stator of the bacterial flagellar motor is formed from the membrane proteins
      MotA and MotB, which associate in complexes with stoichiometry MotA(4)MotB(2)
      (Kojima, S., and Blair, D. F., preceding paper in this issue). The MotA/MotB
      complexes conduct ions across the membrane, and couple ion flow to flagellar
      rotation by a mechanism that appears to involve conformational changes within the
      complex. MotA has four membrane-crossing segments, termed A1-A4, and MotB has
      one, termed B. We are studying the organization of the 18 membrane segments in
      the MotA(4)MotB(2) complex by using targeted disulfide cross-linking. A previous
      cross-linking study showed that the two B segments in the complex (one from each
      MotB subunit) are arranged as a symmetrical dimer of alpha-helices. Here, we
      extend the cross-linking study to segments A3 and A4. Single Cys residues were
      introduced by mutation in several consecutive positions in segments A3 and A4,
      and double mutants were made by pairwise combination of subsets of the Cys
      replacements in segments A3, A4, and B. Disulfide cross-linking of the single-
      and double-Cys proteins was studied in whole cells, in membranes, and in
      detergent solution. Several combinations of Cys residues in segments A3 and B
      gave a high yield of disulfide-linked MotA/MotB heterodimer upon oxidation with
      iodine. Positions of efficient cross-linking identify a helix face on segment A3
      that is in proximity to segment(s) B. Some combinations of Cys residues in
      segments A4 and B also gave a significant yield of disulfide-linked heterodimer,
      indicating that segment A4 is also near segment(s) B. Certain combinations of Cys
      residues in segments A3 and A4 cross-linked to form MotA tetramers in high yield
      upon oxidation. The high-yield positions identify faces on A3 and A4 that are at
      an interface between MotA subunits. Taken together with mutational studies and
      patterns of amino acid conservation, the cross-linking results delineate the
      overall arrangement of 10 membrane segments in the MotA/MotB complex, and
      identify helix faces likely to line the proton channels.

PMID- 14705930
TI  - Extension of the binding motif of the Sin3 interacting domain of the Mad family
      proteins.
AB  - Sin3 forms the scaffold for a multiprotein corepressor complex that silences
      transcription via the action of histone deacetylases. Sin3 is recruited to the
      DNA by several DNA binding repressors, such as the helix-loop-helix proteins of
      the Mad family. Here, we elaborate on the Mad-Sin3 interaction based on a binding
      study, solution structure, and dynamics of the PAH2 domain of mSin3 in complex to
      an extended Sin3 interacting domain (SID) of 24 residues of Mad1. We show that
      SID residues Met7 and Glu23, outside the previously defined minimal binding
      motif, mediate additional hydrophobic and electrostatic interactions with PAH2.
      On the basis of these results we propose an extended consensus sequence
      describing the PAH2-SID interaction specifically for the Mad family, showing that
      residues outside the hydrophobic core of the SID interact with PAH2 and modulate
      binding affinity to appropriate levels.

PMID- 14705931
TI  - Metal ion stabilization of the U-turn of the A37 N6-dimethylallyl-modified
      anticodon stem-loop of Escherichia coli tRNAPhe.
AB  - Nucleoside base modifications can alter the structures, dynamics, and metal ion
      binding properties of transfer RNA molecules and are important for accurate
      aminoacylation and for maintaining translational fidelity and efficiency. The
      unmodified anticodon stem-loop from Escherichia coli tRNA(Phe) forms a
      trinucleotide loop in solution, but Mg(2+) and dimethylallyl modification of
      A(37) N6 disrupt the loop conformation and increase the mobility of the loop and
      loop-proximal nucleotides. We have used NMR spectroscopy to investigate the
      binding and structural effects of multivalent cations on the unmodified and
      dimethylallyl-modified anticodon stem-loops from E. coli tRNA(Phe). The divalent
      cation binding sites were probed using Mn(2+) and Co(NH(3))(6)(3+). These ions
      bind along the major groove of the stem and associate with the anticodon loop on
      the major groove side in a nonspecific manner. Co(NH(3))(6)(3+) stabilizes the U
      turn conformation of the loop in the dimethylallyl-modified molecule, and the
      chemical shift changes that accompany Co(NH(3))(6)(3+) binding are similar to
      those observed with the addition of Mg(2+). The base-phosphate and base-2'-OH
      hydrogen bonds that characterize the UNR U-turn motif lead to spectral signatures
      in the form of unusual (15)N and (1)H chemical shifts and reduced solvent
      exchange of the U(33) 2'-OH and N3H protons. The unmodified molecule also
      displays spectral features of the U-turn fold in the presence of
      Co(NH(3))(6)(3+), but the loop has additional conformations and is dynamic. The
      results indicate that charge neutralization by a polyvalent cation is sufficient
      to promote formation of the U-turn fold. However, base modification is necessary
      to destabilize competing alternative conformers even for a purine-rich loop
      sequence that is predicted to have strongly favorable base stacking energy.

PMID- 14705932
TI  - Structural and dynamic studies on ligand-free adenylate kinase from Mycobacterium
      tuberculosis revealed a closed conformation that can be related to the reduced
      catalytic activity.
AB  - Tuberculosis is the leading cause of death worldwide from a single infectious
      disease. Search of new therapeutic tools requires the discovery and biochemical
      characterization of new potential targets among the bacterial proteins essential
      for the survival and virulence. Among them are the nucleoside monophosphate
      kinases, involved in the nucleotide biosynthesis. In this work, we determined the
      solution structure of adenylate kinase (AK) from Mycobacterium tuberculosis
      (AKmt), a protein of 181 residues that was found to be essential for bacterial
      survival. The structure was calculated by a simulated annealing protocol and
      energy minimization using experimental restraints, collected by nuclear magnetic
      resonance spectroscopy. The final, well-defined 20 NMR structures show an average
      root-mean-square deviation of 0.77 A for the backbone atoms in regular secondary
      structure segments. The protein has a central CORE domain, composed of a five
      stranded parallel beta-sheet surrounded by seven alpha-helices, and two
      peripheral domains, AMPbd and LID. As compared to other crystallographic
      structures of free form AKs, AKmt is more compact, with the AMP(bd) domain closer
      to the CORE of the protein. Analysis of the (15)N relaxation data enabled us to
      obtain the global rotational correlation time (9.19 ns) and the generalized order
      parameters (S(2)) of amide vectors along the polypeptide sequence. The protein
      exhibits restricted movements on a picosecond to nanosecond time scale in the
      secondary structural regions with amplitudes characterized by an average S(2)()
      value of 0.87. The loops beta1/alpha1, beta2/alpha2, alpha2/alpha3,
      alpha3/alpha4, alpha4/beta3, beta3/alpha5, alpha6/alpha7 (LID), alpha7/alpha8,
      and beta5/alpha9 exhibit rapid fluctuations with enhanced amplitudes. These
      structural and dynamic features of AKmt may be related to its low catalytic
      activity that is 10-fold lower than in their eukaryote counterparts.

PMID- 14705933
TI  - Tryptophan substitutions reveal the role of nicotinic acetylcholine receptor
      alpha-TM3 domain in channel gating: differences between Torpedo and muscle-type
      AChR.
AB  - A recent tryptophan scanning of the alpha-TM3 domain of the Torpedo californica
      AChR demonstrated that this domain can modulate ion-channel gating [Guzman, G.,
      Santiago, J., Ricardo, A., Marti-Arbona, R., Rojas, L., Lasalde-Dominicci, J.
      (2003) Biochemistry 42, 12243-12250]. Here we extend the study of the alpha-TM3
      domain to the muscle-type AChR by examining functional consequences of single
      tryptophan substitutions at five conserved positions (alphaM282, alphaF284,
      alphaV285, alphaA287, and alphaI290) homologous to the alpha-TM3 positions that
      were recently characterized in the Torpedo AChR. Similarly to the Torpedo AChR,
      mutations alphaM282W and alphaV285W, which are presumed to face the interior of
      the protein, did not exhibit functional channel activity. Nevertheless,
      significant expression levels of these mutants were observed at the oocyte
      surface. In contrast to the Torpedo AChR, in the muscle-type AChR, tryptophan
      substitution at positions F284, A287, and I290 produces a significant increase in
      normalized macroscopic response. Single-channel recordings at low ACh
      concentration revealed that the increase in AChR sensitivity for the F284W,
      A287W, and I290W is due to an increase in the mean open duration. These results
      suggest that tryptophan substitution directly affects channel gating, primarily
      the channel closing rate. Our results suggest that residues facing the interior
      of the protein (i.e., alphaM282 and alphaV285) may similarly affect channel
      gating in Torpedo and muscle-type AChR. However, equivalent mutations (i.e.,
      F284W and I290W) presumably facing the lipid environment display a very different
      functional response between these two AChR species.

PMID- 14705934
TI  - Balanol analogues probe specificity determinants and the conformational
      malleability of the cyclic 3',5'-adenosine monophosphate-dependent protein kinase
      catalytic subunit.
AB  - The protein kinase family is a prime target for therapeutic agents, since
      unregulated protein kinase activities are linked to myriad diseases. Balanol, a
      fungal metabolite consisting of four rings, potently inhibits Ser/Thr protein
      kinases and can be modified to yield potent inhibitors that are selective
      characteristics of a desirable pharmaceutical compound. Here, we characterize
      three balanol analogues that inhibit cyclic 3',5'-adenosine monophosphate
      dependent protein kinase (PKA) more specifically and potently than calcium- and
      phospholipid-dependent protein kinase (PKC). Correlation of thermostability and
      inhibition potency suggests that better inhibitors confer enhanced protection
      against thermal denaturation. Crystal structures of the PKA catalytic (C) subunit
      complexed to each analogue show the Gly-rich loop stabilized in an "intermediate"
      conformation, disengaged from important phosphoryl transfer residues. An analogue
      that perturbs the PKA C-terminal tail has slightly weaker inhibition potency. The
      malleability of the PKA C subunit is illustrated by active site residues that
      adopt alternate rotamers depending on the ligand bound. On the basis of sequence
      homology to PKA, a preliminary model of the PKC active site is described. The
      balanol analogues serve to test the model and to highlight differences in the
      active site local environment of PKA and PKC. The PKA C subunit appears to
      tolerate balanol analogues with D-ring modifications; PKC does not. We attribute
      this difference in preference to the variable B helix and C-terminal tail. By
      understanding the details of ligand binding, more specific and potent inhibitors
      may be designed that differentiate among closely related AGC protein kinase
      family members.

PMID- 14705935
TI  - Mutational analysis provides molecular insight into the carbohydrate-binding
      region of calreticulin: pivotal roles of tyrosine-109 and aspartate-135 in
      carbohydrate recognition.
AB  - Calreticulin (CRT) is a lectin chaperone present in the lumen of the endoplasmic
      reticulum. It interacts with various glycoproteins by binding via their attached
      Glc(1)Man(9)GlcNAc(2) moiety. To provide further insight into these lectin-glycan
      interactions, we are investigating the interaction of CRT with various sugars. We
      have earlier modeled the complex between CRT and the Glc(1)Man(3)
      tetrasaccharide, a derivative of the native Glc(1)Man(9)GlcNAc(2) sugar moiety.
      Here, we have systematically mutated the residues implicated by the model in the
      interaction of CRT to its sugar substrates and categorized the role played by
      each of the subsites of calreticulin toward the glycan binding. The CRT mutants
      Y109F and D135L did not show any binding to the sugar substrates interacting with
      the wild-type protein, demonstrating the great importance of these residues in
      the carbohydrate-binding site of CRT. Also, D317L and M131A showed weak affinity
      toward the trisaccharide. The mutation of residues from the primary binding site
      of CRT, i.e., those interacting with glucose, appears to be far less tolerated as
      compared to mutations in residues that interact with the mannose residues of the
      glycan. Also, methyl-2-deoxy-glucopyranosyl-alpha(1-->3)-mannopyranoside failed
      to bind, asserting to the significance of the interactions between the primary
      binding site of CRT and the 2'-OH of the glucose residue of the oligosaccharide
      substrate in generating specificity for this recognition. These studies provide
      detailed molecular insight into the sugar binding specificity of CRT.

PMID- 14705936
TI  - Signal recognition particle Alu domain occupies a defined site at the ribosomal
      subunit interface upon signal sequence recognition.
AB  - The eukaryotic signal recognition particle (SRP) is essential for cotranslational
      targeting of proteins to the endoplasmic reticulum (ER). The SRP Alu domain is
      specifically required for delaying nascent chain elongation upon signal sequence
      recognition by SRP and was therefore proposed to interact directly with
      ribosomes. Using protein cross-linking, we provide experimental evidence that the
      Alu binding protein SRP14 is in close physical proximity of several ribosomal
      proteins in functional complexes. Cross-linking occurs even in the absence of a
      signal sequence in the nascent chain demonstrating that SRP can bind to all
      translating ribosomes and that close contacts between the Alu domain and the
      ribosome are independent of elongation arrest activity. Without a signal
      sequence, SRP14 cross-links predominantly to a protein of the large subunit. Upon
      signal sequence recognition, certain cross-linked products become detectable or
      more abundant revealing a change in the Alu domain-ribosome interface. At this
      stage, the Alu domain of SRP is located at the ribosomal subunit interface since
      SRP14 can be cross-linked to proteins from the large and small ribosomal
      subunits. Hence, these studies reveal differential modes of SRP-ribosome
      interactions mediated by the Alu domain.

PMID- 14705937
TI  - Crystallographic analysis of the interaction of nitric oxide with quaternary-T
      human hemoglobin.
AB  - In addition to interacting with hemoglobin as a heme ligand to form
      nitrosylhemoglobin, NO can react with cysteine sulfhydryl groups to form S
      nitrosocysteine or cysteine oxides such as cysteinesulfenic acid. Both modes of
      interaction are very sensitive to the quaternary structure of hemoglobin. To
      directly view the interaction of NO with quaternary-T deoxyhemoglobin,
      crystallographic studies were carried out on crystals of deoxyhemoglobin that
      were exposed to gaseous NO under a variety of conditions. Consistent with
      previous spectroscopic studies in solution, these crystallographic studies show
      that the binding of NO to the heme groups of crystalline wild-type
      deoxyhemoglobin ruptures the Fe-proximal histidine bonds of the alpha-subunits
      but not the beta-subunits. This finding supports Perutz's theory that ligand
      binding induces tension in the alpha Fe-proximal histidine bond. To test Perutz's
      theory, deoxy crystals of the mutant hemoglobin betaW37E were exposed to NO. This
      experiment was carried out because previous studies have shown that this mutation
      greatly reduces the quaternary constraints that oppose the ligand-induced
      movement of the alpha-heme Fe atom into the plane of the porphyrin ring. As
      hypothesized, the Fe-proximal histidine bonds in both the beta- and the alpha
      subunits remain intact in crystalline betaW37E after exposure to NO. With regard
      to S-nitrosocysteine or cysteine oxide formation, no evidence for the reaction of
      NO with any cysteine residues was detected under anaerobic conditions. However,
      when deoxyhemoglobin crystals are first exposed to air and then to NO, the
      appearance of additional electron density indicates that Cys93(F9)beta has been
      modified, most likely to cysteinesulfenic acid. This modification of
      Cys93(F9)beta disrupts the intrasubunit salt bridge between His146(HC3)beta and
      Asp94(FG1)beta, a key feature of the quaternary-T hemoglobin structure. Also
      presented is a reanalysis of our previous crystallographic studies [Chan, N.-L.,
      et al. (1998) Biochemistry 37, 16459-16464] of the interaction of NO with
      liganded hemoglobin in the quaternary-R2 structure. These studies showed
      additional electron density at Cys93(F9)beta that was consistent with an NO
      adduct. However, for reasons discussed in this paper, we now believe that this
      adduct may be the Hb-S-N.-O-H radical intermediate and not Hb-S-N=O as previously
      suggested.

PMID- 14705938
TI  - Crystal structure of the ancient, Fe-S scaffold IscA reveals a novel protein
      fold.
AB  - IscA belongs to an ancient family of proteins responsible for iron-sulfur cluster
      assembly in essential metabolic pathways preserved throughout evolution. We
      report here the 2.3 A resolution crystal structure of Escherichia coli IscA, a
      novel fold in which mixed beta-sheets form a compact alpha-beta sandwich domain.
      In contrast to the highly mobile secondary structural elements within the
      bacterial Fe-S scaffold protein IscU, a protein which is thought to have a
      similar function, the great majority of the amino acids that are conserved in
      IscA homologues are located in elements that constitute a well-ordered fold.
      However, the 10-residue C-terminal tail segment that contains two invariant
      cysteines critical for the Fe-S-binding function of a cyanobacterial
      (Synechocystis PCC) IscA homologue is not ordered in our structure. In addition,
      the crystal packing reveals a helical assembly that is constructed from two
      possible tetrameric oligomers of IscA.

PMID- 14705939
TI  - Using nanoparticle optics assay for direct observation of the function of
      antimicrobial agents in single live bacterial cells.
AB  - Multidrug resistance (MDR) has been reported in both prokaryotes and eukaryotes,
      underscoring the challenge of design and screening of more efficacious new drugs.
      For instance, the efflux pump of Pseudomonas aeruginosa (gram-negative bacteria)
      can extrude a variety of structurally and functionally diverse substrates, which
      leads to MDR. In this study, we present a new platform that studies modes of
      action of antibiotics in living bacterial cells (P. aeruginosa), in real-time, at
      nanometer scale and single-cell resolution using nanoparticle optics and single
      living cell imaging. The color index of silver (Ag) nanoparticles (violet, blue,
      green, and red) is used as the sized index (30 +/- 10, 50 +/- 10, 70 +/- 10, and
      90 +/- 10 nm) for real-time measurement of sized transformation of the cell wall
      and membrane permeability at the nanometer scale. We have demonstrated that the
      number of Ag nanoparticles accumulated in cells increases as the aztreonam (AZT)
      concentration increases and as incubation time increases, showing that AZT
      induces the sized transformation of membrane permeability and the disruption of
      the cell wall. The results demonstrate that nanoparticle optics assay can be used
      as a new powerful tool for real-time characterization of modes of action of
      antimicrobial agents in living cells at the nanometer scale. Furthermore, studies
      of mutants of WT bacteria (nalB-1 and DeltaABM), suggest that an efflux pump
      (MexA-MexB-OprM) effectively extrudes substrates (nanoparticles) out of the
      cells, indicating that the MDR mechanism involves the induction of changes in
      membrane permeability and the intrinsic pump machinery.

PMID- 14705940
TI  - Partitioning of fish and insect antifreeze proteins into ice suggests they bind
      with comparable affinity.
AB  - Antifreeze proteins (AFPs) inhibit the growth of ice by binding to the surface of
      ice crystals, preventing the addition of water molecules to cause a local
      depression of the freezing point. AFPs from insects are much more effective at
      depressing the freezing point than fish AFPs. Here, we have investigated the
      possibility that insect AFPs bind more avidly to ice than fish AFPs. Because it
      is not possible to directly measure the affinity of an AFP for ice, we have
      assessed binding indirectly by examining the partitioning of proteins into a
      slowly growing ice hemisphere. AFP molecules adsorbed to the surface and became
      incorporated into the ice as they were overgrown. Solutes, including non-AFPs,
      were very efficiently excluded from ice, whereas AFPs became incorporated into
      ice at a concentration roughly equal to that of the original solution, and this
      was independent of the AFP concentration in the range (submillimolar) tested.
      Despite their >10-fold difference in antifreeze activity, fish and insect AFPs
      partitioned into ice to a similar degree, suggesting that insect AFPs do not bind
      to ice with appreciably higher affinity. Additionally, we have demonstrated that
      steric mutations on the ice binding surface that decrease the antifreeze activity
      of an AFP also reduce its inclusion into ice, supporting the validity of using
      partitioning measurements to assess a protein's affinity for ice.

PMID- 14705941
TI  - Molecular dissection of a critical specificity determinant within the amino acid
      editing domain of leucyl-tRNA synthetase.
AB  - A highly conserved threonine residue marks the amino acid binding pocket within
      the editing active site of leucyl-tRNA synthetases (LeuRSs). It is essential to
      substrate specificity for the Escherichia coli enzyme in that it blocks the
      cognate leucine amino acid from binding in the hydrolytic editing active site. We
      combined mutagenesis and computational approaches to elucidate the molecular role
      of the critical side chain of this threonine residue. Removal of the terminal
      methyl group of the threonine side chain by replacement with serine yielded a
      mutant LeuRS that hydrolyzes Leu-tRNA(Leu). Substitution of valine for the
      conserved threonine conferred similar activities to the wild-type enzyme.
      However, an additional substitution within the editing active site suggested
      synergistic interactions with the conserved threonine site that significantly
      affected amino acid editing. On the basis of our combined biochemical and
      computational data, we propose that the threonine 252 side chain not only
      sterically hinders the cognate charged leucine from binding for hydrolysis but
      also plays a critical role in maintaining an active site geometry that is
      required for the fidelity of LeuRS.

PMID- 14705942
TI  - Tryptophan spectroscopy studies and black lipid bilayer analysis indicate that
      the oligomeric structure of Cry1Ab toxin from Bacillus thuringiensis is the
      membrane-insertion intermediate.
AB  - During intoxication, the Cry protoxins must change from insoluble crystals into
      membrane-inserted toxins, which form ionic pores. Binding of Cry1A toxins to the
      cadherin receptor promotes the formation of a 250 kDa oligomer. In this work, we
      analyzed for the first time the structural changes presented by Cry1Ab toxin upon
      membrane insertion. Trp fluorescence of pure monomeric and oligomeric structures
      in solution and in a membrane-bound state was analyzed. Cry1Ab has nine Trp
      residues, seven of them in pore-forming domain I. Trp quenching analysis with
      iodide indicated that oligomerization caused a 27% reduction in the level of Trp
      exposed to the solvent. Most of the oligomeric structure (96%) inserts into the
      membrane as a function of the lipid:protein ratio, in contrast to the monomer
      (10%). Additionally, the membrane-associated oligomer presented a blue shift of 5
      nm in lambda(max) of the emission spectrum, indicating a more hydrophobic
      environment for some Trp residues. In agreement with this, iodide was unable to
      quench the Trp of the membrane-bound oligomer, suggesting that a significant part
      of the protein may be buried in the membrane. Quenching analysis using brominated
      and spin-labeled phospholipids in the vesicles indicates that most of the Trp
      residues are located close to the membrane-water interface. Finally, ionic
      currents in black lipid bilayers revealed that the oligomeric structure has
      kinetics different from those of the monomer, producing stable channels with a
      high probability of being open in contrast to the monomer that exhibited unstable
      opening patterns. These data show that the oligomer, in contrast to the monomer,
      is able to interact efficiently with phospholipid membranes forming stable pores.

PMID- 14705943
TI  - Single live cell imaging of chromosomes in chloramphenicol-induced filamentous
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a leading opportunistic pathogen in human infections,
      and it is renowned for its intrinsic resistance to structurally and functionally
      unrelated antibiotics. Filamentation induced by antibiotics appears to trigger
      bacteria to depart from a normal growth phase and enter a stationary growth
      phase. As antibiotic concentrations decline below a therapeutic range,
      filamentous bacteria begin to divide normally, leading to a more rapid regrowth
      of the bacteria. Furthermore, filamentous bacteria are associated with an
      increase in endotoxin release. Moreover, the immune system of a patient needs to
      cope with uncharacteristic filamentous bacteria. Thus, it is biologically and
      clinically significant to study and understand bacterial filamentation. In this
      study, we investigate the frequencies, conditions, and characteristics of a
      filamentous P. aeruginosa at single cell and single chromosome resolutions. Our
      results show that filamentous cells (elongated rods) contain multiple copies of
      the cell's chromosome. It appears that the unsuccessful segregation of replicated
      chromosomes in an individual cell accompanies the formation of undivided
      filamentous cells. The quantity of chromosomes and the length of the filamentous
      wild-type cells increase as the chloramphenicol concentration increases to 50 and
      250 microg/mL, suggesting that chloramphenicol induces the filamentation.
      Filamentation in three strains of P. aeruginosa depends on the expression level
      of efflux pump (MexAB-OprM) and the minimum inhibitory concentration of
      chloramphenicol. This study also opens up the new possibility of real-time
      monitoring of modes of actions of antibiotics in live cells with both temporal
      and spatial resolution.

PMID- 14705944
TI  - Toward the elucidation of the catalytic mechanism of the mono-ADP
      ribosyltransferase activity of Pseudomonas aeruginosa exotoxin A.
AB  - The catalytic mechanism for the mono-ADP-ribosyltransferase activity of
      Pseudomonas aeruginosa exotoxin A was investigated by steady-state and stopped
      flow kinetic analyses. The rate constants for binding of the NAD(+) substrate to
      the enzyme were found to be 4.7 +/- 0.4 microM(-1) s(-1) and 194 +/- 15 s(-1) for
      k(on) and k(off), respectively. The k(on) and k(off) rate constants for the eEF-2
      substrate binding to the enzyme were 320 +/- 39 microM(-1) s(-1) and 131 +/- 22
      s(-1), respectively. A potent, competitive inhibitor against the enzyme, 1,8
      naphthalimide, bound the enzyme with k(on) and k(off) rates of 82 +/- 9 microM(
      1) s(-1) and 51 +/- 6 s(-1), respectively. Furthermore, the binding on and off
      rates for the reaction products, ADP-ribose and nicotinamide, were too rapid for
      detection with the stopped-flow technique. Investigation of the pre-steady-state
      kinetics for the ADP-ribose transferase activity of the toxin-enzyme showed that
      there is no pre-steady-state complex formed during the catalytic cycle. Binding
      of NAD+ and smaller compounds representing the various parts of this substrate
      were investigated by the fluorescence quenching of the intrinsic toxin
      fluorescence. The binding data revealed a significant structural change in the
      enzyme upon NAD+ binding that could not be accounted for on the basis of the sum
      of the structural changes induced by the various NAD+ constituents. Product
      inhibition studies were conducted with nicotinamide and eEF-2-ADP-ribose, and the
      results indicate that the reaction involves a random-order ternary complex
      mechanism. Detailed kinetic analysis revealed that the eEF-2 substrate shows
      sigmoidal kinetic behavior with the enzyme, and fluorescence resonance energy
      transfer measurements indicated that wheat germ eEF-2 is oligomeric in solution.

PMID- 14705945
TI  - Blotting analysis of native IRP1: a novel approach to distinguish the different
      forms of IRP1 in cells and tissues.
AB  - Iron regulatory protein 1 (IRP1) is a bifunctional protein, which either has
      aconitase activity or binds to specific mRNA structures to regulate the
      expression of iron proteins. Using recombinant human IRP1, we found that the two
      functional forms are resolved by nondenaturing polyacrylamide gel electrophoresis
      and that they are distinguished from IRP1/RNA complexes. This allowed us to use
      specific antibodies to develop a blotting system that recognized the iron-free
      and iron-containing IRP1 forms in the soluble fraction and the RNA-bound IRP1 in
      the high-speed precipitate fraction of cell extracts. The system was used to
      study IRP1 in HeLa, K562 cells, and monocytes/macrophages before and after
      treatment with iron salts, iron chelators, or hydrogen peroxide, as well as in
      stomach and duodenum biopsies. The results showed that iron-bound aconitase IRP1
      is by far the prevalent form in most cells and that the major effect of cellular
      iron modifications is a shift between free and RNA-bound IRP1. The fraction of
      RNA-bound IRP1 was highly variable among different cells and was often a minor
      one. Furthermore, blotting showed that electrophoretic mobility shift assay, as
      commonly used, tends to under-evaluate the amount of total IRP1 and to over
      evaluate the actual RNA-binding activity of IRP1. In conclusion, blotting
      analysis of IRP1 is a new, useful, and convenient method to analyze the amount
      and conformations of the protein that reveals previously undetected differences
      in IRP1 compartmentalization among various cell types.

PMID- 14705946
TI  - Redox properties of human transferrin bound to its receptor.
AB  - Virtually all organisms require iron, and iron-dependent cells of vertebrates
      (and some more ancient species) depend on the Fe(3+)-binding protein of the
      circulation, transferrin, to meet their needs. In its iron-donating cycle,
      transferrin is first captured by the transferrin receptor on the cell membrane,
      and then internalized to a proton-pumping endosome where iron is released. Iron
      exits the endosome to enter the cytoplasm via the ferrous iron transporter DMT1,
      a molecule that accepts only Fe(2+), but the reduction potential of ferric iron
      in free transferrin at endosomal pH (approximately 5.6) is below -500 mV, too low
      for reduction by physiological agents such as the reduced pyridine nucleotides
      with reduction potentials of -284 mV. We now show that in its complex with the
      transferrin receptor, which persists throughout the transferrin-to-cell cycle of
      iron uptake, the potential is raised by more than 200 mV. Reductive release of
      iron from transferrin, which binds Fe(2+) very weakly, is therefore
      physiologically feasible, a further indication that the transferrin receptor is
      more than a passive conveyor of transferrin and its iron.

PMID- 14705947
TI  - Regulation of the enzymatic catalysis of poly(ADP-ribose) polymerase by dsDNA,
      polyamines, Mg2+, Ca2+, histones H1 and H3, and ATP.
AB  - The enzymatic mechanism of poly(ADP-ribose) polymerase (PARP-1) has been analyzed
      in two in vitro systems: (a) in solution and (b) when the acceptor histones were
      attached to a solid surface. In system (a), it was established that the
      coenzymatic function of dsDNAs was sequence-independent. However, it is apparent
      from the calculated specificity constants that the AT homopolymer is by far the
      most effective coenzyme and randomly damaged DNA is the poorest. Rates of
      auto(poly-ADP-ribosylation) with dsDNAs as coenzymes were nearly linear for 20
      min, in contrast to rates with dcDNA, which showed product [(ADPR)n] inhibition.
      An allosteric activation of auto(poly-ADP-ribosylation) by physiologic cellular
      components, Mg2+, Ca2+, and polyamines, was demonstrated, with spermine as the
      most powerful activator. On a molar basis, histones H(1) and H(3) were the most
      effective PARP-1 activators, and their action was abolished by acetylation of
      lysine end groups. It was shown in system (b) that oligo(ADP-ribosyl) transfer to
      histone H(1) is 1% of that of auto(poly-ADP-ribosylation) of PARP-1, and this
      trans(ADP-ribosylation) is selectively regulated by putrescine (activator).
      Physiologic cellular concentrations of ATP inhibit PARP-1 auto(poly-ADP
      ribosylation) but less so the transfer of oligo(ADP-ribose) to histones,
      indicating that PARP-1 auto(ADP-ribosylation) activity is dormant in
      bioenergetically intact cells, allowing only trans(ADP-ribosylation) to take
      place. The inhibitory mechanism of ATP on PARP-1 consists of a noncompetitive
      interaction with the NAD site and competition with the coenzymic DNA binding
      site. A novel regulation of PARP-1 activity and its chromatin-related functions
      by cellular bioenergetics is proposed that occurs in functional cells not exposed
      to catastrophic DNA damage.

PMID- 14705948
TI  - Analysis of nucleotide sequence-dependent DNA binding of poly(ADP-ribose)
      polymerase in a purified system.
AB  - The enzymatic transfer of ADP-ribose from NAD to histone H(1) [defined as
      trans(oligo-ADP-ribosylation)] or to PARP-1 [defined as auto(poly-ADP
      ribosylation)] requires binding of coenzymic DNA. The preceding paper [Kun, E.,
      et al. (2004) Biochemistry 43, 210-216] shows that oligonucleotides of dsDNA can
      serve as coenzymic DNA for PARP-1 trans- or auto-modification activity. Results
      of DNA-protein binding (EMSA) experiments reported here demonstrate that short
      DNA oligonucleotides containing the 5'-TGTTG-3' nucleotide sequence motif
      preferentially bind to cloned PARP-1 in vitro. The same nucleotide sequence motif
      is responsible for striated myocyte-selective transcription of a contractile
      protein gene encoding cardiac troponin T (cTnT). Results of experiments reported
      here demonstrate that mutation of this motif also abolishes the differentiation
      dependent activation of the transfected cTnT promoter in myoblasts cultured in
      vitro, indicating that nucleotide sequence-dependent binding of PARP-1 to
      promoter DNA of the cTnT gene is also necessary for differentiation-dependent
      activation. Thus, PARP-1 has two types of dsDNA binding activity: (1) nucleotide
      sequence-dependent binding, analyzed here with EMSA experiments, and (2)
      coenzymic binding, measured catalytically, which does not depend on the
      nucleotide sequence of the dsDNA. We hypothesize that the well-known association
      of PARP-1 with chromatin can be attributed to its stable binding to chromosomal
      dsDNA, some portion of which is likely to be nucleotide sequence-dependent
      binding. According to this hypothesis, the distribution of this protein-modifying
      enzyme in chromatin may be targeted to specific genomic loci and vary according
      to cell type and developmental stage.

PMID- 14705949
TI  - Evolution of enzymatic activity in the enolase superfamily: functional studies of
      the promiscuous o-succinylbenzoate synthase from Amycolatopsis.
AB  - o-Succinylbenzoate synthase (OSBS) from Amycolatopsis, a member of the enolase
      superfamily, catalyzes the Mn2+-dependent exergonic dehydration of 2-succinyl-6R
      hydroxy-2,4-cyclohexadiene-1R-carboxylate (SHCHC) to 4-(2'-carboxylphenyl)-4
      oxobutyrate (o-succinylbenzoate or OSB) in the menaquinone biosynthetic pathway.
      This enzyme first was identified as an N-acylamino acid racemase (NAAAR), with
      the optimal substrates being the enantiomers of N-acetyl methionine. This
      laboratory subsequently discovered that this protein is a much better catalyst of
      the OSBS reaction, with the value of k(cat)/K(M), for dehydration, 2.5 x 10(5) M(
      1) s(-1), greatly exceeding that for 1,1-proton transfer using the enantiomers of
      N-acetylmethionine as substrate, 3.1 x 10(2) M(-1) s(-1) [Palmer, D. R., Garrett,
      J. B., Sharma, V., Meganathan, R., Babbitt, P. C., and Gerlt, J. A. (1999)
      Biochemistry 38, 4252-8]. The efficiency of the promiscuous NAAAR reaction is
      enhanced with alternate substrates whose structures mimic that of the SHCHC
      substrate for the OSBS reaction, for example, the value of k(cat)/K(M) for the
      enantiomers of N-succinyl phenylglycine, 2.0 x 10(5) M(-1) s(-1), is comparable
      to that for the OSBS reaction. The mechanisms of the NAAAR and OSBS reactions
      have been explored using mutants of Lys 163 and Lys 263 (K163A/R/S and
      K263A/R/S), the putative acid/base catalysts identified by sequence alignments
      with other OSBSs, including the structurally characterized OSBS from Escherichia
      coli. Although none of the mutants display detectable OSBS or NAAAR activities,
      K163R and K163S catalyze stereospecific exchange of the alpha-hydrogen of N
      succinyl-(S)-phenylglycine with solvent hydrogen, and K263R and K263 catalyze the
      stereospecific exchange the alpha-hydrogen of N-succinyl-(R)-phenylglycine,
      consistent with formation of a Mn2+-stabilized enolate anion intermediate. The
      rates of the exchange reactions catalyzed by the wild-type enzyme exceed those
      for racemization. That this enzyme can catalyze two different reactions, each
      involving a stabilized enediolate anion intermediate, supports the hypothesis
      that evolution of function in the enolase superfamily proceeds by pathways
      involving functional promiscuity.

PMID- 14705950
TI  - Folding of Aplysia limacina apomyoglobin involves an intermediate in common with
      other evolutionarily distant globins.
AB  - In the globin family, similarities in the folding mechanism have been found among
      different mammalian apomyoglobins (apoMb). The best-characterized intermediate of
      sperm whale apoMb, called I(AGH), is mainly stabilized by nativelike contacts
      among the A, G, and H helices involving a cluster of hydrophobic residues that
      includes two conserved tryptophans. To verify the hypothesis of a common
      intermediate in the folding of all members of the globin family, we have
      extensively studied a site-directed mutant of the myoglobin from Aplysia
      limacina, distantly related to the mammalian counterpart, in which one of the two
      tryptophans in the A-G-H cluster [i.e., Trp(H8)130] has been mutated to tyrosine.
      The results presented here show that this mutation destabilizes both the native
      state and the acid intermediate I(A) but exerts little or no effect on the
      thermally stable core of an intermediate species (called I(T)) peculiar to
      Aplysia apomyoglobin. Dynamic quenching of Trp emission by acrylamide provides
      information on the accessibility of the chromophores at the native and the
      intermediate states of wild-type and mutant Aplysia apomyoglobin, consistent with
      the thermodynamics. Our results agree well with those obtained for the
      corresponding topological position of apomyoglobin from sperm whale and clearly
      show that the H8 position is involved in the stabilization of the main
      intermediate in both apoproteins. This residue thus plays a role which is
      evolutionarily conserved in the globin family from invertebrates to mammals; our
      results support the contention that the A-G-H cluster is important in the folding
      pathway of different globins.

PMID- 14705951
TI  - Heparan sulfate proteoglycans are involved in opiate receptor-mediated cell
      migration.
AB  - Opioid receptors are expressed in cells of the immune system, and potent
      immunomodulatory effects of their natural and synthetic ligands have been
      reported. In some studies, the opiate receptor antagonist naloxone itself
      displayed immunomodulatory actions. We investigated effects of naloxone on
      leukocyte chemotaxis. Cell migration was tested in micropore filter assays using
      modified Boyden chambers, and receptor expression was investigated using
      radiolabel binding assays. Naloxone induced peripheral blood nonadherent
      mononuclear cell and neutrophil chemotaxis at nanomolar concentrations and
      deactivated their migration toward beta-endorphin, angiotensin II, somatostatin,
      or interleukin-8 but not toward RANTES, vasoactive intestinal peptide, or
      substance P. Ligand binding studies showed no alteration in the binding of
      interleukin-8 to neutrophils by naloxone. Cleavage of heparan sulfate from
      proteoglycans on the cells' surface completely inhibited chemotactic and
      deactivating properties of naloxone but not other attractants. Chemotactic
      properties were abolished by pretreating cells with heparinase, chondroitinase,
      sodium chlorate, and anti-syndecan-4 antibodies, indicating the involvement of
      syndecan-4. The extent of migration toward naloxone was diminished by
      pretreatment with dimethylsphingosine, a specific sphingosine kinase inhibitor.
      As syndecan-4 signaling in leukocyte chemotaxis involves activation of
      sphingosine kinase, results indicate that naloxone interacts with syndecan-4
      function in cell migration and suggest a role for heparan sulfate proteoglycans
      as coreceptors to members of the delta-opiate receptor family.

PMID- 14705952
TI  - Structure/activity relationships for GMEB-2: the second member of the
      glucocorticoid modulatory element-binding complex.
AB  - The position of the dose-response curve of agonist complexes of glucocorticoid
      receptors (GRs), and the partial agonist activity of GR-antagonist complexes, can
      be modulated by two proteins (GMEB-1 and -2), which bind as oligomers to a DNA
      element that is called a glucocorticoid modulatory element, or GME. This element
      is active when located upstream of the glucocorticoid response element that
      controls the expression of a reporter gene. Here, we report the
      structure/activity relationships of GMEB-2 and compare them to our previous
      findings for GMEB-1. Most of the activities of GMEB-2, such as homo- and
      heterooligomerization, binding to GR and to CBP, DNA binding, and modulation of
      the above GR transcriptional properties, require large regions of the protein.
      Only the intrinsic transactivation activity could be localized to a small region
      of the protein. These studies shed light on the mechanism of action of GMEB-2 and
      further support our previous conclusion that the ability of factors to modulate
      the position of the dose-response curve, and the partial agonist activity, of GR
      complexes is unrelated to effects on the total levels of GR-induced gene
      expression. These studies also identify regions of GMEB-2 possessing yet
      unidentified properties that are critical for several activities. Finally, as the
      domain organization of GMEB-2 and -1 is extremely similar, we conclude that the
      quantitative differences in activities derive from variations in amino acid
      sequence rather than more global features of protein structure.

PMID- 14705953
TI  - Lateral membrane protein associations of CD4 in lymphoid cells detected by cross
      linking and mass spectrometry.
AB  - Interactions of membrane proteins are important in various aspects of cell
      function. However, weak membrane protein-protein interactions are difficult to
      study using techniques such as co-immunoprecipitations. CD4 is a cell surface
      protein involved in T cell activation and the binding of the human
      immunodeficiency virus to HIV target cells. Here we report the use of cross
      linking followed by affinity purification of CD4 in combination with mass
      spectrometry for identification of proteins that are in the proximity of CD4.
      Besides the components of the CD4 receptor complex, CD4 and lck, we have
      identified by tandem mass spectrometry 17 tryptic peptides from transferrin
      receptor CD71, three peptides from protein phosphatase CD45, and one peptide from
      4F2 lymphocyte activation antigen CD98. The efficiency of the cross-linking did
      not correlate with the level of cell surface expression of the detected
      molecules, excluding a possible bias of the cross-linking toward the most
      abundant cell surface molecules. Whereas the association of CD4 with CD45 has
      been reported, the associations with CD71 and CD98 have not been previously
      described. We used small-scale immunoprecipitation after cross-linking in
      combination with fluorescence resonance energy transfer (FRET) measurements to
      investigate the association between CD4 and CD71. Our data show that CD71 self
      associates on the cell surface, that a small fraction of CD4 can be detected by
      copurifying it with CD71 after cross-linking, and that the level of association
      between CD4 and CD71 significantly increases after phorbol 12-myristate 13
      acetate-induced endocytosis of CD4. This suggests that a small fraction of CD4
      associates with clusters of CD71. As both molecules undergo endocytic recycling,
      the association and cross-linking result from their clustering in the same pit
      and/or vesicle. The CD4-CD98 association probably results from nonspecific cross
      linking.

PMID- 14705954
TI  - Regulation of signal peptidase by phospholipids in membrane: characterization of
      phospholipid bilayer incorporated Escherichia coli signal peptidase.
AB  - Prokaryotic signal peptidases are membrane-bound enzymes. They cleave signal
      peptides from precursors of secretary proteins. To study the enzyme in its
      natural environment, which is phospholipid bilayers, we developed a method that
      allows us effectively to incorporate full-length Escherichia coli signal
      peptidase I into phospholipid vesicles. The membrane-bound signal peptidase
      showed high activity on a designed substrate. The autolysis site of the enzyme is
      separated from its catalytic site in vesicles by the lipid bilayer, resulting in
      a dramatic decrease of the autolysis rate. Phosphotidylethanolamine, which is the
      most abundant lipid in Escherichia coli inner membrane, is required to maintain
      activity of the membrane-incorporated signal peptidase. The maximal activity is
      achieved at about 55% phosphotidylethanolamine. Negatively charged lipids, which
      are also abundant in Escherichia coli inner membrane, enhances the activity of
      the enzyme too. Its mechanism, however, cannot be fully explained by its ability
      to increase the affinity of the substrate to the membrane. A reaction mechanism
      was developed based on the observation that cleavage only takes place when the
      enzyme and the substrate are bound to the same vesicle. Accordingly, a kinetic
      analysis is presented to explain some of the unique features of phospholipid
      vesicles incorporated signal peptidase, including the effect of lipid
      concentration and substrate-vesicle interaction.

PMID- 14705955
TI  - Steady-state kinetic investigation of cytochrome P450cam: interaction with redox
      partners and reaction with molecular oxygen.
AB  - Cytochrome P450cam (CYP101) is a prokaryotic monooxygenase that requires two
      proteins, putidaredoxin reductase (PdR) and putidaredoxin (Pdx), to supply
      electrons from NADH. This study addresses the mechanism by which electrons are
      transported from PdR to P450cam through Pdx and used to activate O(2) at the heme
      of P450cam. It is shown that k(cat)/Km(O2) is independent of the PdR
      concentration and hyperbolically dependent on Pdx. The phenomenon of saturation
      of reaction rates with either P450cam or PdR at high ratios of one enzyme to the
      other is investigated and shown to be consistent with a change in the rate
      limiting step. Either the reduction of Pdx by PdR (high P450) or the reduction of
      P450 by Pdx (high PdR) determines the rate. These data support a mechanism where
      Pdx acts as a shuttle for transport of electrons from PdR to P450cam, effectively
      ruling out the formation of a kinetically significant PdR/Pdx/P450cam complex.

PMID- 14705956
TI  - Rate-limiting guanosine 5'-triphosphate hydrolysis during nucleotide turnover by
      FtsZ, a prokaryotic tubulin homologue involved in bacterial cell division.
AB  - FtsZ is a prokaryotic tubulin homologue that polymerizes into a dynamic ring
      during cell division. GTP binding and hydrolysis provide the energy for FtsZ
      dynamics. However, the precise role of hydrolysis in polymer assembly and
      turnover is not understood, limiting our understanding of how FtsZ functions in
      the cell. Here we investigate GTP hydrolysis during the FtsZ polymerization cycle
      using several complementary approaches that avoid technical caveats of previous
      studies. We find that at steady state approximately 80% of FtsZ polymer subunits
      are bound to GTP. In addition, we use pre-steady-state, single turnover assays to
      directly measure the rate of hydrolysis. Hydrolysis was found to occur at
      approximately 8/min and to be a rate-limiting step in GTP turnover; phosphate
      release rapidly followed. These results clarify previously conflicting results in
      the literature and suggest that pure FtsZ polymers, unlike microtubules, may not
      be able to undergo dynamic instability or to store energy in the polymer for
      force production.

PMID- 14705957
TI  - Pluripotent differentiation in vitro of murine ES-D3 embryonic stem cells.
AB  - Although the ES-D3 murine embryonic stem cell line was one of the first derived,
      little information exists on the in vitro differentiation potential of these
      cells. We have used immunocytochemical and flow cytometric methods to monitor ES
      D3 embryoid body differentiation in vitro during a 21-d period. Spontaneous
      differentiation of embryoid body cells was induced by leukemia inhibitory factor
      withdrawal in the absence of feeder cells. The pluripotent stem cell markers Oct
      3/4, SSEA-1, and EMA-1 were found to persist for at least 7 d, whereas the
      primitive endoderm marker cytokeratin endo-A was expressed at increasing levels
      from day 6. The localization of these antigens within the embryoid bodies
      suggested that embryonic ectoderm- and primitive endoderm-derived tissues were
      segregated. Localized expression of class III beta-tubulin and sarcomeric myosin
      also was detected, indicating that representatives of all three embryonic germ
      layers were present after induction of differentiation in vitro.

PMID- 14705959
TI  - Identification and characterization of the conserved nucleoside-binding sites in
      the Epstein-Barr virus thymidine kinase.
AB  - Thymidine kinase (TK), encoded by EBV (Epstein-Barr virus), is an attractive
      target for antiviral therapy and provides a novel approach to the treatment of
      EBV-associated malignancies. Despite the extensive use of nucleoside analogues
      for the treatment of viral infections and cancer, the structure-function
      relationship of EBV TK has been addressed rarely. In the absence of any
      structural information, we sought to identify and elucidate the functional roles
      of amino acids in the nucleoside-binding site using site-directed mutagenesis.
      Through alignment with other human herpesviral TK protein sequences, we predicted
      that certain conserved regions comprise the nucleoside-binding site of EBV TK
      and, through site-directed mutagenesis, showed significant changes in activity
      and binding affinity for thymidine of site 3 (-DRH-) and 4 (-VFP-) mutants. For
      site 3, only mutants D392E (Asp392-->Glu) and R393H retain activity, indicating
      that a negative charge is important for Asp392 and a positive charge is required
      for Arg393. The increased binding affinities of these two mutants for 3'-deoxy
      2',3'-didehydrothymidine suggest that the two residues are also important for
      substrate selection. Interestingly, the changed metal-ion usage pattern of D392E
      reveals that Asp392 plays multiple roles in this region. His394 cannot be
      compensated by other amino acids, also indicating a crucial role. In site 4, the
      F402Y mutant retains full activity; however, F402S retains only 60% relative
      activity. Strikingly, when Phe402 is substituted with serine residue, the
      original preferred pyrimidine substrates, such as 3'-azido-3'-deoxythymidine,
      iododeoxyuridine and beta-L-5-iododioxolane uracil (L-form substrate), have
      decreased competitiveness with thymidine, suggesting that Phe402 plays a crucial
      role in substrate specificity and that the aromatic ring is important for
      function.

PMID- 14705960
TI  - Evolutionary families of peptidase inhibitors.
AB  - The proteins that inhibit peptidases are of great importance in medicine and
      biotechnology, but there has never been a comprehensive system of classification
      for them. Some of the terminology currently in use is potentially confusing. In
      the hope of facilitating the exchange, storage and retrieval of information about
      this important group of proteins, we now describe a system wherein the inhibitor
      units of the peptidase inhibitors are assigned to 48 families on the basis of
      similarities detectable at the level of amino acid sequence. Then, on the basis
      of three-dimensional structures, 31 of the families are assigned to 26 clans. A
      simple system of nomenclature is introduced for reference to each clan, family
      and inhibitor. We briefly discuss the specificities and mechanisms of the
      interactions of the inhibitors in the various families with their target enzymes.
      The system of families and clans of inhibitors described has been implemented in
      the MEROPS peptidase database (http://merops.sanger.ac.uk/), and this will
      provide a mechanism for updating it as new information becomes available.

PMID- 14705961
TI  - The periplasmic serine protease inhibitor ecotin protects bacteria against
      neutrophil elastase.
AB  - Ecotin is a dimeric periplasmic protein from Escherichia coli that has been shown
      to inhibit potently many trypsin-fold serine proteases of widely varying
      substrate specificity. To help elucidate the physiological function of ecotin, we
      examined the family of ecotin orthologues, which are present in a subset of Gram
      negative bacteria. Phylogenetic analysis suggested that ecotin has an exogenous
      target, possibly neutrophil elastase. Recombinant protein was expressed and
      purified from E. coli, Yersinia pestis and Pseudomonas aeruginosa, all species
      that encounter the mammalian immune system, and also from the plant pathogen
      Pantoea citrea. Notably, the Pa. citrea variant inhibits neutrophil elastase 1000
      fold less potently than the other orthologues. All four orthologues are dimeric
      proteins that potently inhibit (<10 pM) the pancreatic digestive proteases
      trypsin and chymotrypsin, while showing more variable inhibition (5 pM to 24
      microM) of the blood proteases Factor Xa, thrombin and urokinase-type plasminogen
      activator. To test whether ecotin does, in fact, protect bacteria from neutrophil
      elastase, an ecotin-deficient strain was generated in E. coli. This strain is
      significantly more sensitive in cell-killing assays to human neutrophil elastase,
      which causes increased permeability of the outer membrane that persists even
      during renewed bacterial growth. Ecotin affects primarily the ability of E. coli
      to recover and grow following treatment with neutrophil elastase, rather than the
      actual rate of killing. This suggests that an important part of the antimicrobial
      mechanism of neutrophil elastase may be a periplasmic bacteriostatic effect of
      protease that has translocated across the damaged outer membrane.

PMID- 14705962
TI  - New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for
      beta-aminoisobutyric acid?
AB  - DPD (dihydropyrimidine dehydrogenase) constitutes the first step of the
      pyrimidine degradation pathway, in which the pyrimidine bases uracil and thymine
      are catabolized to beta-alanine and the R-enantiomer of beta-AIB (beta
      aminoisobutyric acid) respectively. The S-enantiomer of beta-AIB is predominantly
      derived from the catabolism of valine. It has been suggested that an altered
      homoeostasis of beta-alanine underlies some of the clinical abnormalities
      encountered in patients with a DPD deficiency. In the present study, we
      demonstrated that only a slightly decreased concentration of beta-alanine was
      present in the urine and plasma, whereas normal levels of beta-alanine were
      present in the cerebrospinal fluid of patients with a DPD deficiency. Therefore
      the metabolism of beta-alanine-containing peptides, such as carnosine, may be an
      important factor involved in the homoeostasis of beta-alanine in patients with
      DPD deficiency. The mean concentration of beta-AIB was approx. 2-3-fold lower in
      cerebrospinal fluid and urine of patients with a DPD deficiency, when compared
      with controls. In contrast, strongly decreased levels (10-fold) of beta-AIB were
      present in the plasma of DPD patients. Our results demonstrate that, under
      pathological conditions, the catabolism of valine can result in the production of
      significant amounts of beta-AIB. Furthermore, the observation that the R
      enantiomer of beta-AIB is abundantly present in the urine of DPD patients
      suggests that significant cross-over exists between the thymine and valine
      catabolic pathways.

PMID- 14705963
TI  - Two novel non-cationic defensin-like antimicrobial peptides from haemolymph of
      the female tick, Amblyomma hebraeum.
AB  - Two non-cationic defensin-like antimicrobial peptides, named Amblyomma defensin
      peptide 1 and Amblyomma defensin peptide 2, were identified from the hard tick,
      Amblyomma hebraeum, by a combination of suppression subtractive hybridization for
      differentially expressed genes and proteomics. cDNA clones encoding each of these
      two defensin-like antimicrobial peptides were isolated from the differentially
      expressed cDNA library of the tick synganglia (central nervous system). The
      preproproteins deduced from the cDNA sequences each have 92 amino acid residues.
      Amblyomma defensin peptide 2 was purified from the haemolymph of fed female
      ticks. The purified peptide displayed antibacterial activity against Gram
      negative and Gram-positive bacteria. Amblyomma defensin peptide 1 was further
      identified by protein chip capture combined with SELDI-TOF (surface-enhanced
      laser desorption/ionization-time-of-flight) MS. By screening for differentially
      expressed proteins, it was found that the expression of Amblyomma defensin
      peptide 1 was upregulated during 4 days post-feeding. Our findings firstly
      provide two defensin-like antimicrobial peptides that are particularly novel in
      being anionic, together with corresponding cDNA sequences, in hard ticks, and
      prove that the combination of suppression subtractive hybridization and protein
      profiling is a powerful method to study differentially expressed proteins,
      especially for organisms without available genome sequence information.

PMID- 14705964
TI  - Kinetic analysis of ligand-induced autocatalytic reactions.
AB  - Protein phosphorylation and limited proteolysis are two most common regulatory
      mechanisms involving the energy-dependent covalent modification of regulatory
      enzymes. In addition to modifying other proteins, many protein kinases and
      proteases catalyse automodification reactions (i.e. reactions in which the kinase
      or zymogen serves as its own substrate), and their activities are frequently
      regulated by other regulatory ligands. In the present study, a kinetic analysis
      of autocatalytic reaction modulated by regulatory ligands is presented. On the
      basis of the kinetic equation, a novel procedure is developed to evaluate the
      kinetic parameters of the reaction. As an example of an application of this
      method, the effects of calcium ions on the autoacatalytic activation of
      trypsinogen by trypsin is re-examined. The results indicate that the binding
      affinity for Ca2+-bound trypsinogen to trypsin is at least two orders of
      magnitude higher than that for Ca2+-free trypsinogen, and therefore that the
      effect of Ca2+ ions on K(m*) values for trypsinogen is very much greater than
      that for the model peptides. Based on the experimental results, one possible
      molecular mechanism has been proposed.

PMID- 14705965
TI  - Characterization of the Drosophila protein arginine methyltransferases DART1 and
      DART4.
AB  - The role of arginine methylation in Drosophila melanogaster is unknown. We
      identified a family of nine PRMTs (protein arginine methyltransferases) by
      sequence homology with mammalian arginine methyltransferases, which we have named
      DART1 to DART9 ( Drosophila arginine methyltransferases 1-9). In keeping with the
      mammalian PRMT nomenclature, DART1, DART4, DART5 and DART7 are the putative
      homologues of PRMT1, PRMT4, PRMT5 and PRMT7. Other DART family members have a
      closer resemblance to PRMT1, but do not have identifiable homologues. All nine
      genes are expressed in Drosophila at various developmental stages. DART1 and
      DART4 have arginine methyltransferase activity towards substrates, including
      histones and RNA-binding proteins. Amino acid analysis of the methylated arginine
      residues confirmed that both DART1 and DART4 catalyse the formation of
      asymmetrical dimethylated arginine residues and they are type I arginine
      methyltransferases. The presence of PRMTs in D. melanogaster suggest that flies
      are a suitable genetic system to study arginine methylation.

PMID- 14705966
TI  - Numerous transcriptional alterations in liver persist after short-term enzyme
      replacement therapy in a murine model of mucopolysaccharidosis type VII.
AB  - The lysosomal storage disease MPS VII (mucopolysaccharidosis type VII) is caused
      by a deficiency in beta-glucuronidase activity, and results in the accumulation
      of partially degraded glycosaminoglycans in many cell types. Although MPS VII is
      a simple monogenetic disorder, the clinical presentation is complex and
      incompletely understood. ERT (enzyme replacement therapy) is relatively effective
      at improving the clinical course of the disease; however, some pathologies
      persist. In order to clarify the molecular events contributing to the disease
      phenotype and how ERT might impact upon them, we analysed liver tissue from
      untreated and treated MPS VII mice at both 2 and 5 months of age using
      biochemical assays and microarray analysis. Overall, as the disease progresses,
      more genes have altered expression and, at either age, numerous transcriptional
      changes in multiple pathways appear to be refractory to therapy. With respect to
      the primary site of disease, both transcriptional and post-transcriptional
      mechanisms are involved in the regulation of lysosomal enzymes and other lysosome
      associated proteins. Many of the changes observed in both lysosome-associated
      mRNAs and proteins are normalized by enzyme replacement. In addition, gene
      expression changes in seemingly unrelated pathways may account for the complex
      metabolic phenotype of the MPS VII mouse. In particular, beta-glucuronidase
      deficiency appears to induce physiological malnutrition in MPS VII mice.
      Malnutrition may account for the pronounced adipose storage deficiency observed
      in this animal. Studying the molecular response to lysosomal storage, especially
      those changes recalcitrant to therapy, has revealed additional targets that may
      improve the efficacy of existing therapies.

PMID- 14705968
TI  - Fractionated, stereotactic proton beam treatment of cerebral arteriovenous
      malformations.
AB  - OBJECTIVES: To evaluate the therapeutic efficiency and adverse effects of
      stereotactic proton beam treatment of cerebral arteriovenous malformations (AVM).
      MATERIAL AND METHODS: Twenty-six patients treated in Uppsala during 1991-97 were
      included (men = 14, women = 12; mean age = 39, range = 23-64). The nidus volumes
      ranged from 0.3 to 102 ml (mean = 24, median = 13). The follow-up included
      clinical evaluation, magnetic resonance imaging (and/or computed tomography)
      every 6-12 months for 3 years and final angiography. RESULTS: The volume changes
      at final follow-up in AVMs >25 ml were -89, -85, -44, -29, -7, 0, 0, +5 and +18
      (%); in AVMs 11-24 ml, -100, -100, -97, -92 and 0 (%); and in AVMs <10 ml, -100, 
      100, -100, -100, -100, -99, -98, -50, -0 and +40 (%). Two patients were lost to
      follow-up due to cerebral haemorrhage and myocardial infarction. Radiology
      displayed significant perifocal oedema in one patient and slight oedema in four
      patients. Of nine patients with epilepsy, seven became seizure-free after therapy
      while two continued to suffer from seizures. CONCLUSION: Proton beam irradiation
      is successful in a relatively high proportion of intermediate and large-sized
      cerebral AVMs. The adverse effects are acceptable. The advantage of proton
      treatment compared with gamma knife and LINAC stereotactic irradiation is that
      protons can irradiate even large volumes with a very sharp dose profile against
      normal surroundings. Thus, proton beam irradiation is a valuable option in the
      treatment of AVMs larger than 10 ml.

PMID- 14705969
TI  - Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function
      and 3D-CBF.
AB  - OBJECTIVE: The reason for longstanding fatigue following aneurysmal
      subarachnoidal hemorrhage (SAH) is still not clarified. The bleed from
      supratentorial aneurysms is often in the vicinity of the hypothalamus and
      pituitary gland making an endocrine dysfunction plausible. METHODS: Ten patients
      with post-SAH fatigue were investigated with 3D-CBF (SPECT) and underwent an
      evaluation of the pituitary function. RESULTS: Five had normal pituitary
      function. Disturbances in the gonadotropin function was detected in three
      patients and suspected in two. The mean insulin-like growth factor I (IGF-I)
      value of the patients was in the lower part of the reference range. In the
      patients with endocrine dysfunction, the 3D-CBF was pathologic in the central
      structures of the basal region. CONCLUSIONS: The present results indicate that an
      aneurysmal SAH may result in partially impaired pituitary capacity. This deficit
      may contribute to fatigue after aneurysmal SAH, but cannot solely explain this
      disorder. SPECT identified regional tissue damage in the patients with pituitary
      dysfunction after SAH.

PMID- 14705967
TI  - Studies on regulation of IGF (insulin-like growth factor)-binding protein (IGFBP)
      4 proteolysis by pregnancy-associated plasma protein-A (PAPP-A) in cells treated
      with phorbol ester.
AB  - PAPP-A (pregnancy-associated plasma protein-A) is produced by hSFs (human skin
      fibroblasts) and hOBs (human osteoblasts) and enhances the mitogenic activity of
      IGFs (insulin-like growth factors) by degradation of IGFBP-4 (insulin-like growth
      factor-binding protein 4). PKC (protein kinase C) activation in these cells led
      to reduction in IGFBP-4 proteolysis. This study was undertaken to determine the
      mechanism by which activation of PKC suppresses IGFBP-4 proteolysis. Treatment of
      hSFs/hOBs with TPA (PMA; 100 nM) reduced IGFBP-4 proteolysis without
      significantly decreasing the PAPP-A level in the CM (conditioned medium).
      Immunodepletion of the proform of eosinophil major basic protein (proMBP), a
      known PAPP-A inhibitor, from CM of TPA-treated cells (TPA CM) failed to increase
      IGFBP-4 proteolytic activity. Transduction of hSFs with proMBP retrovirus
      increased the concentration of proMBP up to 30 ng/ml and led to a moderate
      reduction in IGFBP-4 proteolysis. In contrast, TPA treatment blocked IGFBP-4
      proteolysis but failed to induce a detectable amount of proMBP in the CM. While
      proMBP overexpression led to the formation of a covalent proMBP-PAPP-A complex
      and reduced the migration of PAPP-A on SDS/PAGE, TPA treatment dose- and time
      dependently increased the conversion of a approximately 470 kDa PAPP-A form (PAPP
      A470) to a approximately 400 kDa PAPP-A form (PAPP-A400). Since unreduced PAPP
      A400 co-migrated with the 400 kDa recombinant PAPP-A homodimer and since PAPP-A
      monomers from reduced PAPP-A470 and PAPP-A400 co-migrated on SDS/PAGE, conversion
      of PAPP-A470 to PAPP-A400 is unlikely to be caused by proteolytic cleavage of
      PAPP-A. Consistent with the data showing that the increase in the ratio of PAPP
      A400/PAPP-A470 is correlated with the extent of reduction in IGFBP-4 proteolysis,
      partially purified PAPP-A400 exhibited a 4-fold reduction in IGFBP-4 proteolytic
      activity compared with PAPP-A470. These data suggest that a novel mechanism,
      namely conversion of PAPP-A470 to the less-active PAPP-A400, could account for
      the TPA-induced suppression of PAPP-A activity.

PMID- 14705970
TI  - Cerebrospinal fluid markers in MS patients and their healthy siblings.
AB  - In a previous study we found that nine of 47 siblings to multiple sclerosis (MS)
      patients with a normal neurological examination carry an intrathecal oligoclonal
      immunopathy with limited specificity, a condition we termed MS immunopathic
      trait. The purpose of this study is to further characterize the MS immunopathic
      trait phenotype. We found that the neurofilament light protein (NFL) and glial
      fibrillary acidic protein (GFAp) concentrations were increased in the group of
      patients with clinically definite MS (n = 47) in latent or slowly progressive
      phases. There was no increase in GFAp and NFL in cerebrospinal fluid in the
      healthy siblings of MS patients (n = 47), nor in the subgroup of these siblings
      with MS immunopathic trait (n = 9) compared with a group of healthy control
      subjects (n = 50). Thus, there was no indication of presymptomatic CNS
      parenchymal involvement in MS immunopathic trait.

PMID- 14705971
TI  - Urodynamic findings in primary progressive multiple sclerosis are associated with
      increased volumes of plaques and atrophy in the central nervous system.
AB  - OBJECTIVE: Voiding dysfunction is more frequent in primary progressive multiple
      sclerosis (PPMS) than in other subtypes of MS. We investigated whether lower
      urinary tract disorders are reflected in the extent of changes in brain and
      spinal cord detected by magnetic resonance imaging (MRI). METHODS: Micturition
      symptoms and specific urodynamic findings in 24 patients with PPMS were related
      to MRI abnormalities as analysed by segmentation and volumetric analysis.
      RESULTS: Urgency and urge incontinence were the most frequent urinary symptoms
      (83 and 75 %), while detrusor sphincter dyssynergia (DSD) (71%), detrusor
      hyperreflexia (58%) and obstruction (58%) were the most common micturition
      dysfunctions. Comparison between patients with detrusor hyperreflexia and those
      with normal bladder function revealed higher volumes of T2-weighted plaques in
      the brains of former (P = 0.01). In patients with hypotonic bladder the total
      brain volume was smaller (P = 0.02) and the number of thoracic plaques in T2
      weighted images higher (P = 0.02) compared to patients with normal bladder
      function. Furthermore, DSD was associated with a higher volume of T2-weighted
      plaques in the brain (P = 0.02). CONCLUSIONS: Voiding dysfunction in PPMS is
      associated with increasing brain and spinal cord abnormalities. Urodynamic
      investigation is, however, needed for specific definition of micturition
      disturbances and should be made before therapeutic decisions.

PMID- 14705972
TI  - Oligoclonal IgG bands synthesized in the central nervous system are present in
      rats with experimental autoimmune encephalomyelitis.
AB  - OBJECTIVE: Oligoclonal bands (OBs) in electrophoresis of cerebrospinal fluid
      (CSF) are present in multiple sclerosis and here is investigated whether these
      also occur in experimental autoimmune encephalomyelitis (EAE). MATERIAL AND
      METHODS: Experimental autoimmune encephalomyelitis was induced in 42 DA rats
      after immunization with rat spinal chord homogenate and the occurrence of OBs
      were detected by electrophoresis of both sera and CSF. The relationship between
      disease symptoms, antibody response against myelin basic protein (MBP), myelin
      oligodendrocyte glycoprotein (MOG) and appearance of OBs was studied. RESULTS:
      Development of CSF-specific OB was found to occur, 6 weeks after immunization, in
      seven of 42 rats. OB was detected in rats with an antibody response against MBP,
      whereas as a role no such bands were present in rats with an antibody response
      against MOG. Initially severe disease symptoms were correlated to a concomitant
      intense oligoclonal antibody response. CONCLUSION: Cerebrospinal fluid-specific
      OB occurs in EAE. It is present in rats with an anti-MBP, but not in rats with an
      anti-MOG antibody response. A severe disease results in an intense oligoclonal
      antibody response, which might have an anti-inflammatory effect.

PMID- 14705973
TI  - Quality of life in hereditary neuromuscular diseases.
AB  - OBJECTIVE: The aim of the study is to evaluate different aspects in the quality
      of life (QoL) in a group of patients affected by hereditary neuromuscular
      disease. MATERIAL AND METHODS: Forty-five consecutive outpatients (mean age 49.46
      +/- 17.07 years, range 19-80 years) with hereditary neuromuscular disease
      underwent the Brooke scale and functional independent measure to assess the
      functional status, the Sickness Impact Profile (SIP) and Psychological General
      Well-Being Index (PGWBI), as a measure of the QoL. RESULTS AND CONCLUSIONS: All
      patients had a poor QoL assessment with SIP. The higher disability level was not
      related to a worse QoL perception with the exception of the physical area.
      Females and patients above 49 years showed the worst QoL profile. The discomfort
      linked to the emotional and affective sphere, assessed with PGWBI, appeared low
      in the study sample. Therefore psychosocial aspects and economical and
      environmental factors may influence the QoL.

PMID- 14705974
TI  - Lifestyle and late effects after poliomyelitis. A risk factor study of two
      populations.
AB  - BACKGROUND: Patients with polio often experience new symptoms (muscle weakness,
      pain, fatigue and respiratory problems) many years after the acute disease. This
      study examined possible interactions between lifestyle factors (overweight,
      physical inactivity, smoking) and late polio with new symptoms. METHODS: A total
      of 148 patients hospitalized for acute polio in 1950-1954 at Haukeland University
      Hospital, Norway and 128 patients, hospitalized for acute polio in 1958 at Tartu
      University Hospital, Estonia responded to a mailed questionnaire regarding
      lifestyle and late polio with new symptoms. Multiple regression analysis, two
      samples t-test and chi-square analysis were undertaken. RESULTS: Mean body mass
      index (BMI) and percentage of smokers did not differ in the two cohorts, while
      polio patients were physically less active in Estonia. The physically active
      patients in both cohorts had significantly lower odds for experiencing polio
      related late muscle pain (OR = 0.21; 95% CI = 0.08-0.55) and fatigue (OR = 0.32;
      95% CI = 0.14-0.75). With increasing age the patients had significantly higher
      odds for experiencing new muscle weakness (OR = 1.03; 95% CI = 1.00-1.07),
      fatigue (OR = 1.04;95% CI = 1.01-1.07) and breath shortness (OR = 1.04; 95% CI =
      1.00-1.07). CONCLUSION: Physically inactive patients are at a higher risk for
      late polio-related symptoms. An active lifestyle should be recommended for
      patients with polio sequels.

PMID- 14705975
TI  - Temporal lobe epilepsy: analysis of patients with dual pathology.
AB  - OBJECTIVES: To determine the frequency and types of dual pathology in patients
      with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and
      surgical outcome. MATERIAL AND METHODS: A total of 240 patients with TLE
      underwent temporal resections following a comprehensive pre-surgical evaluation.
      Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe
      gliosis in association with another lesion (dual pathology). RESULTS: Eighteen of
      37 patients with dual pathology had heterotopia of the temporal lobe, nine had
      cortical dysplasia, four had cavernous angiomas or arteriovenous malformations,
      one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four
      patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic
      resonance imagings, 91.3% had abnormal positron emission tomography scans, and
      96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed
      impaired memory of the epileptogenic side in 72% of the patients. Twenty patients
      had left and 17 had right-sided en bloc temporal resections, including the lesion
      and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight
      (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one
      (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years).
      CONCLUSIONS: 15.4% had dual pathology. The dual pathology was almost exclusively
      seen in patients whose lesions were congenital, or occurred early in life,
      suggesting that the hippocampus is more vulnerable and more readily develops HS
      in early childhood. Resections, including the lateral and mesial temporal
      structures led to a favorable outcome with no mortality and little morbidity.

PMID- 14705976
TI  - No evidence for loss of hippocampal neurons in non-Alzheimer dementia patients.
AB  - OBJECTIVE: To use stereological methods for estimating the total number of
      neurons in hippocampi of non-Alzheimer demented patients. MATERIAL AND METHODS:
      Hippocampi from six women with severely impaired memory but without Alzheimer
      pathology were compared with six mentally intact age-matched female controls. The
      total number of neurons was estimated in the granule cell layer of the dentate
      gyrus, the hilus of the dentate gyrus, the pyramidal cell layer of CA3 and CA2,
      the pyramidal cell layer of CA1 and the cellular layer of subiculum using the
      optical fractionator. RESULTS: The total neuron number was the same in the
      dementia cases, 22.4 x 106, compared with 22.7 x 106 in the controls (P = 0.85).
      No region-specific group differences or side difference were found. Two cases
      without clinical signs of dementia but with abundant plaques and tangles in
      hippocampus and neocortex had total neuron numbers within normal limits.
      CONCLUSION: Our results indicate that severely impaired memory can occur in the
      presence of intact numbers of hippocampal neurons in non-Alzheimer dementia and
      that nerve cell loss in the hippocampus might be characteristic for Alzheimer's
      disease, and perhaps other forms of primary cortical dementia.

PMID- 14705977
TI  - Association between apolipoprotein CI HpaI polymorphism and sporadic Alzheimer's
      disease in Chinese.
AB  - OBJECTIVE: To investigate into the relationship of apolipoprotein CI (ApoCI)
      polymorphism with sporadic Alzheimer's disease (AD) in Chinese. SUBJECTS AND
      METHODS: A total of 257 AD patients and 242 age-matched elderly individuals were
      genotyped for the ApoCI HpaI and apolipoprotein E (ApoE) HhaI polymorphisms.
      RESULTS: The ApoCI A allele was associated with AD of moderate to severe dementia
      when patients were divided into two subgroups according to Clinical Dementia
      Rating scale, and the AA genotype was strongly associated with moderate to severe
      AD in ApoE epsilon4 allele carriers [odds ratio (OR) = 8.19, 95% confidential
      interval: 1.28-52.30, after adjusting for age and gender by logistic regression
      analysis], although in total no significant differences of allele or genotype
      frequency between patients and controls were found. CONCLUSION: The present study
      partially confirmed the previous findings, suggesting that the ApoCI A allele
      might contribute to the susceptibility to moderate to severe sporadic AD in
      Chinese.

PMID- 14705978
TI  - Transcranial magnetic stimulation to the parietal lobes reduces detection of
      contralateral somatosensory stimuli.
AB  - OBJECTIVES: Neglect has been described in patients with lesions of the parietal
      cortex and has been interpreted as a disorder of the allocation of spatial
      attention. The persistence of neglect has been linked to poor rehabilitation
      outcome in patients suffering from acute stroke. Transcranial magnetic
      stimulation (TMS) applied to the parietal cortex has been shown to induce changes
      in the perception of stimuli including tactile stimulation of the fingers contra-
      and ipsilateral to the stimulated hemisphere. MATERIAL AND METHODS: In the
      current study, eleven normal young subjects performed a detection task for
      cutaneous electrical stimuli to the left or right forearm that had been precued
      by a preceding visual warning stimulus. To investigate the role of the parietal
      cortical areas for attentional processes TMS was applied to frontal and parietal
      scalp sites of each hemisphere in the cue-target interval before the
      somatosensory stimulus. RESULTS: Right and left parietal stimulation led to
      reduced detection sensitivity for near threshold stimuli to the forearm
      contralateral to the stimulated hemisphere without hemispheric differences.
      Ipsilateral tactile perception was not influenced by parietal TMS and there was
      no change in perception after frontal stimulation to left or right scalp sites.
      CONCLUSION: This pattern of results is consistent with a role of the right and
      left parietal lobe in the distribution of spatial attention and provides an
      experimental basis for possible therapeutical application of TMS to improve
      attentional deficits in stroke patients.

PMID- 14705979
TI  - Gene conversion events in adult-onset spinal muscular atrophy.
AB  - OBJECTIVE: To investigate the possible occurrence of a conversion event in three
      patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents
      the mildest form within the spectrum of the SMA phenotype. MATERIAL AND METHODS:
      We observed three patients with adult onset SMA and apparent isolated deletion of
      telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion
      and a sequence conversion event of exon 7, these patients were analyzed in
      greater detail by a simple PCR-based assay. RESULTS: Analysis by DdeI digestion
      showed products for both telomeric and centromeric copies of exon 8. These
      findings indicated a gene conversion event as the site for primer R111 was
      retained at least in one of two alleles. CONCLUSIONS: These results provide first
      evidence that a conversion event may be also associated with adult-onset SMA, and
      further support the notion that a gene conversion event is usually associated
      with a milder SMA phenotype and a later onset of disease.

PMID- 14705980
TI  - Occurrence of atypical parkinsonism in Indians and Caucasians.

PMID- 14705981
TI  - The structural basis of T-cell allorecognition.
AB  - Foreign allogeneic major histocompatibility complex (MHC) class I and class II
      molecules elicit an exceptionally vigorous T-cell response. A small component of
      the alloresponse comprises CD4+ T cells that recognize allogeneic MHC indirectly
      after processing into peptide fragments that are bound and presented by self-MHC
      class II. The majority of alloreactive T cells directly recognize intact
      allogeneic MHC molecules expressed on foreign cells. Some alloreactive T-cell
      interactions with allogeneic MHC molecules are indifferent to the bound peptide,
      but evidence suggests that most show specificity to peptide. The vigor and
      diversity of the direct alloreactive T-cell response can therefore be explained
      by summation of numerous responses to each of the peptides in the novel set bound
      by allogeneic MHC molecules. Structural studies definitively show that the
      overall mechanism of T-cell receptor (TCR) recognition of self-MHC and allogeneic
      MHC molecules is similar. Many alloreactive T cells recognize several different
      combinations of MHC and bound peptide that do not necessarily possess structural
      homology. Flexibility within the TCR structure allows adaptation to the different
      contact surfaces. Crossreactivity seems to be an intrinsic property of the TCR
      required, because a single TCR must possess the ability to interact with both
      self-MHC during positive selection and at least one combination of foreign
      antigenic peptide presented by self-MHC. Recognition of allogeneic MHC molecules
      is an inadvertent consequence of the need for TCR crossreactivity.

PMID- 14705982
TI  - The phylogenies of introns 4-7 demonstrate an inconsistent pattern between human
      leukocyte antigen-C group topologies.
AB  - In this study, we have sequenced introns 4-7 in 31 human leukocyte antigen-C (HLA
      C) alleles representing all allelic groups. Intron sequences show a patchwork
      pattern of polymorphism. Bootstrap support for phylogenetic lineages and for
      differentiation between groups is limited due to the high homology of intron
      sequences, where the substitution of a single nucleotide may lead to the
      assignment to different clusters. The intron data suggest the idea of a
      Cw*06/Cw*12 family, which is closely related to a hypothetical Cw*05/Cw*08
      family. Moreover, a third family consisting of Cw*01/Cw*04/Cw*18 may exist. The
      intron data compiled in our study may be the basis for further sequencing
      studies. The detection of three novel alleles (Cw*0401new, Cw*140201new, and
      Cw*1701new) suggests that the HLA-C polymorphism might have been strongly
      underestimated to date.

PMID- 14705983
TI  - Cloning of a human antibody directed against human neuroblastoma cells and
      specific for human translation elongation factor 1alpha.
AB  - Human sera have shown antitumor effects mediated by tumor-specific immunoglobulin
      M (IgM) antibodies. Most people who have cytotoxic serum are in good health and
      show no evidence of exposure to tumor antigens. We characterized the serum of a
      healthy female adult that was highly lytic to a neuroblastoma cell line via IgM
      activated complement (>60% of malignant cells were killed during the 60-min
      assay). Complement-dependent lysis was not mediated by other classes of serum
      antibodies (data not shown) which is consistent with the findings of Ollert et
      al. To identify the target antigen on neuroblastoma cells, we fractionated
      neuroblastoma cell lysates by ion-exchange chromatography. In the fraction that
      showed maximal IgM binding, the dominant protein was identified as the 47-kDa
      translational elongation factor 1alpha (eEF1alpha). We used the donor's B-cells
      to create hybridomas producing the antibody (B12.6.22) that bound to
      neuroblastoma cells and mediated cytotoxicity. This antibody recognized eEF1alpha
      in a specific manner. Sequence analysis of the heavy chain of B12.6.22 showed
      usage of VH3-23 and JH6 gene segments, with no somatic mutation. The structural
      similarity of B12.6.22 to antibodies of the innate immune system supports the
      assumption that natural antibodies are a potential source of therapeutic
      antibodies.

PMID- 14705984
TI  - MD-1 expression regulates direct and indirect allorecognition.
AB  - Expression of the molecule MD-1 was previously described to regulate allogeneic
      and xenogeneic skin graft survival, as documented by the decrease in rejection
      seen following functional blockade of MD-1 expression in vivo, using antisense
      oligodeoxynucleotides (ODNs) or anti-MD-1 antibodies. It was unclear from these
      data whether blockade of expression of MD-1 on donor or recipient cells was
      crucial. We have investigated the effect on allorecognition of treating skin
      graft donors, and/or recipients, of either fully major histocompatibility complex
      (MHC)-mismatched allogeneic skin grafts (C3H with C57BL/6 grafts and vice versa)
      or grafts differing at only multiple minor alloantigens (C3H with B10.BR grafts;
      C57BL/6 with C3H.SW), with antisense ODNs to MD-1, or in some cases, following
      transplantation of class II-deficient cells into class I-deficient mice. Graft
      specific cytotoxic T lymphocytes (CTLs) were measured in spleen cells recovered
      at sacrifice of recipients and following donor-specific restimulation in vitro.
      In the latter case, we also measured cell proliferation and (by enzyme-linked
      immunosorbent assay) production of interleukin-2 (IL-2)/interferon-gamma (IFN
      gamma) or IL-4/IL-10 in vitro (nominal type-1 vs type-2 cytokines). CTL responses
      to minor-incompatible grafts were diminished, only if graft recipients were
      treated with ODNs. However, treatment of graft donor and/or recipient of MHC
      incompatible grafts produced inhibition of CTL production. Optimal inhibition
      came from treating both. Specific suppression of CTL production coincided with
      inhibition of proliferation and preferential production of IL-4 and IL-10 at the
      expense of IL-2 and IFN-gamma. Our data are consistent with the hypothesis that
      MD-1 expression regulates both the direct and indirect pathways of
      allorecognition and that regulation of MD-1 expression may thus help regulate
      clinical graft rejection.

PMID- 14705985
TI  - The reagent database at dbMHC.
AB  - The reagent database dbMHC was built by the National Center for Biotechnology
      Information (NCBI) as an open resource for registration and characterization of
      HLA DNA-typing kits and reagents. Each reagent is uniquely identified as sequence
      specific oligonucleotide (SSO) or primer (SSP), SSO mix, or SSP mix. Computerized
      prediction of allele reactivities, based on annealing stringency, is performed on
      all submissions to the reagent database. User-specified allele reactivities may
      be added or deleted independently of the prediction algorithm. Updates of allele
      reactivities are performed in synchronization with the IMGT/HLA database, in
      order to account for newly discovered alleles. Probe and primer sequences aligned
      to allelic sequences can be displayed at any time. Reagents registered in the
      reagent database are grouped in typing kits. Each kit or kit batch is uniquely
      identified. Group-specific amplification of alleles can be specified for an
      entire kit or for sections of each kit. Kits designed to test multiple loci are
      supported. Kits can be entered and updated via the web or submitted as batches in
      extensible markup language (XML) format. A tool for online interpretation of
      typing results is available. Both the reagent database and the typing kit
      database have been designed to facilitate the exchange of HLA typing based on raw
      typing data using the unique identifiers of kits or individual reagents. In
      addition, batch-wise reinterpretation of previous typing data can be performed
      either using the NCBI web site or by locally using downloaded allele-reactivity
      lists. Reinterpretation by the NCBI requires submission of raw typing data in XML
      format.

PMID- 14705986
TI  - Differential up-regulation of HLA-DM, invariant chain, and CD83 on myeloid and
      plasmacytoid dendritic cells from peripheral blood.
AB  - Two main dendritic cell (DC) subsets have been described in peripheral blood, the
      myeloid subset or DC1 that is characterized by the presence of CD11c and the
      plasmacytoid subset or DC2 negative for this marker. The two subsets may perform
      different functions and have been defined as immunogenic (the myeloid subset) or
      tolerogenic (the plasmacytoid subset). The expression of human leukocyte antigen
      (HLA)-DM molecules, which act as peptide editors in the antigen presentation
      process, was studied in freshly isolated plasmacytoid and myeloid DCs from
      peripheral blood. The expression of the invariant chain (Ii), the major
      histocompatibility complex class II (MHC-II) : class II-associated Ii peptide
      (CLIP) complex, and CD83 was also investigated. The results showed that
      intracellular expression of HLA-DM and the Ii was significantly higher in the
      plasmacytoid than in the myeloid DC subset. In contrast, a higher fraction of
      cell expressing MHC-II : CLIP complex was found in the myeloid than in the
      plasmacytoid DC subpopulation. CD83 was not detected in any of these two subsets.
      Following culture of these cells with interleukin-3 (IL-3), tumor necrosis factor
      alpha (TNFalpha) and/or heat shock protein-70 (HSP-70), the expression of
      intracellular HLA-DM was up-regulated in the myeloid DCs to levels similar to
      those found in the plasmacytoid DCs, whilst the Ii was down-regulated in the
      plasmacytoid subset to similar levels to those expressed in the myeloid DCs. In
      addition, CD83 was up-regulated in the myeloid (CD11c+) but not in the
      plasmacytoid (CD11c-) DCs. The expression pattern of these antigen-processing
      molecules could be related to the immaturity and function attributed to these DC
      subsets.

PMID- 14705987
TI  - Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from
      North Morocco using sequence-based typing.
AB  - Class I human leukocyte antigen (HLA) polymorphism was examined in a Berber
      population from North Morocco, named Metalsa (ME). All data were obtained at high
      resolution level, using sequence-based typing. The most frequent alleles were:
      HLA-A*0201 and A*0101; HLA-B*44 (B*4403 and B*4402); B*0801 and the B*50 allele
      group (B*5001 and B*5002); HLA-Cw*0602; and Cw*07 group (Cw*070101, Cw*070102,
      Cw*0702, Cw*0704, and Cw*0706), and Cw*040101. The novel HLA-B*570302 allele was
      identified. It differs at position 486 and position 855 from B*570301, resulting
      in synonymous Thr and Val. The analysis also evidenced some alleles common in
      Africans (A*3402, A*6802, A*7401, B*1503, B*4102, B*4202, B*7801, B*5802,
      Cw*1701, and Cw*1703) and some uncommon alleles (A*3004, B*2702, B*2703,
      B*5001,02, B*3503, and Cw*0706). The predominant HLA-A-Cw-B-DRB1-extended
      haplotypes in ME population were A*0101-Cw*0501-B*4402-DRB1*0402, A*240201
      Cw*0701-B*0801-DRB1*030101, A*2301-Cw*040101-B*4403-DRB1*040501, A*0201-Cw*040101
      B*4403-DRB1*1302, and A*3002-Cw*0602-B*5002-DRB1*0406. This study demonstrates a
      strong relatedness of ME to other Moroccan and North African populations, some
      characteristics of sub-Saharan Africans and evidenced the influence of various
      immigrations during centuries. Nevertheless, this study highlights some unique
      genetic traits of the ME population compared to other ethnic groups within
      Morocco, which could be of great interest for clinical aims, transplantation, and
      diseases.

PMID- 14705988
TI  - A new HLA-B44 allele (B*44020102S) with a splicing mutation leading to a complete
      deletion of exon 5.
AB  - Using a combination of serology and polymerase chain reaction with sequence
      specific primer (PCR-SSP), we have identified in a volunteer bone marrow donor a
      new HLA class I antigen within the B44 serotype. This human leukocyte antigen
      (HLA)-B44 variant was typed as 'blank' by microlymphocytotoxicity, whereas the
      B*44020101 allele was identified by PCR-SSP. A family study confirmed the
      Mendelian segregation of this blank antigen identified on one of the maternal
      haplotype transmitted to her child. The DNA sequence of B*44new, now referred to
      as B*44020102S, performed from the promoter region to the 3' untranslated region
      revealed a single nucleotide difference (A/G) compared to B*44020101 at the end
      of intron 4 in the acceptor-splicing site. This mutation leads to an incorrect
      splicing characterized by the deletion of exon 5 that encodes the transmembrane
      domain of the HLA antigen. Indeed, full-length complementary DNA sequencing
      revealed a complete absence of exon 5. Fluorescence-activated cell sorter
      analysis confirmed the absence of expression of HLA-B44 on the cell surface in
      the donor, compared to the HLA-B44 positive control. The isoelectric focusing
      analysis failed to reveal the presence of an HLA-B44 antigen in the donor,
      showing that no normal HLA-B*44020101 allele was synthesized. The new
      B*440201010102S allele is a soluble form of B44 without any detectable cell
      surface expression. It can thus be considered as a soluble antigen, a form
      apparently inactive and unfit for antigen presentation.

PMID- 14705989
TI  - Identification of a novel HLA-F allele - HLA-F*010102.
AB  - We describe herein the identification of HLA-F*010102 by cloning the full-length
      coding sequence with reverse-transcription polymerase chain reaction (RT-PCR).
      This new allele was found in two Han Chinese individuals in the course of cloning
      major histocompatibility complex class Ib (MHC Ib) cDNA. It was identical to HLA
      F*010101 except for a single-nucleotide substitution in codon -1 (GCG --> GCA).
      This nucleotide change represents a synonymous mutation, as both triplets code
      for an alanine. The cDNA of this allele was 48 bp shorter than HLA-F*010101 due
      to splicing out exon 7. Analysis of the deduced amino acid sequence revealed that
      the product of this new allele had the identical extracellular domain and
      transmembrane region but had a shorter cytoplasmic tail.

PMID- 14705990
TI  - Molecular characterization of guinea - pig (Cavia porcellus) CD8alpha and CD8beta
      cDNA.
AB  - CD8 is expressed on cytotoxic T cells (CTL) and functions as a coreceptor for
      recognition of major histocompatibility complex (MHC) class I peptide complexes
      by the T-cell receptor (TCR). The CD8 molecule consists of two subunits (alpha
      and beta) and exists either as a heterodimer (alphabeta) or a homodimer
      (alphaalpha). We report the cloning of full-length cDNAs of guinea pig CD8alpha
      and CD8beta. The deduced amino acid sequence of CD8alpha and CD8beta reveals
      characteristic structural features including a signal peptide, an immunoglobulin
      (Ig) variable-like region, hinge region, transmembrane, and cytoplasmic domains.
      In addition to the full-length cDNA, a splice variant of CD8beta cDNA was
      observed, suggesting splicing events as reported for human CD8beta. The sequence
      homology of guinea pig CD8 indicates greater homology to human, canine, and
      feline counterparts than to rodent CD8. As the guinea pig serves as an ideal non
      primate animal model to several human infectious diseases, such as syphilis,
      tuberculosis, and chlamydial genital and ocular infection, the CD8 sequence
      information provides a necessary molecular tool for studying the cell-mediated
      immune response.

PMID- 14705991
TI  - Nomenclature for factors of the HLA system, update September 2003.

PMID- 14705993
TI  - Guest editorial: SARS--future considerations for nurses.

PMID- 14705995
TI  - The effectiveness of public health nursing: the problems and solutions in
      carrying out a review of systematic reviews.
AB  - BACKGROUND: In 1999 the Scottish Office, United Kingdom, intimated that the Chief
      Nursing Officer would undertake a policy review of nurses' contribution to
      improving the public's health. The importance of reviewing the scientific
      literature on the effectiveness of public health nursing was recognized as a
      crucial part of the policy review. A final report was expected within a 6-month
      period. The reason for the short time period was to fit the policy-making
      schedule. This paper discusses our literature review for this work. AIMS: The aim
      was to conduct a review of the international scientific literature that gave the
      greatest coverage of the role and potential role of nurses in improving the
      public's health in relation to 14 major health topics. This paper describes the
      methods used, outlines the rationale underpinning the methods, discusses the
      problems encountered and offers solutions to some of these problems. METHODS: The
      initial search for relevant scientific literature revealed 709 suitable primary
      papers. Reviewing this number was beyond the time limit set by the funding
      organization. Therefore, a decision was made to concentrate on the evidence
      contained in systematic reviews. Reviewing systematic reviews raises a number of
      methodological problems to which there are often no predetermined solutions, such
      as ensuring that important interventions are included, assessing the relevance
      and quality of the reviews, and grading the strength of the evidence. DISCUSSION:
      Reviewing systematic reviews provides the scope to increase the number of topics
      that might be covered. However, it is possible that a number of interventions may
      be missed, particularly those that are not subject to review or those assessed
      using qualitative techniques. The definition of public health nursing used in the
      present study was also restrictive, and could be widened to include community
      interventions. Finally, assessing the quality of reviews and grading the evidence
      proved difficult and there is lack of consensus on how these tasks should be
      achieved. Nevertheless, the review presented policy makers with accessible
      information on a large number of relevant international studies.

PMID- 14705996
TI  - Expert qualitative researchers and the use of audit trails.
AB  - BACKGROUND: Determining the credibility of qualitative research findings remains
      a contested area and leaves the way open for additional theoretical and
      methodological discussion. AIMS: In this paper we focus on audit trails and
      confirmability, within the context of 'expert' qualitative researchers. Having
      outlined the audit trail process, we develop existing arguments about the
      'expert' qualitative researcher. We then juxtapose the two, highlighting a number
      of issues in an attempt to advance the debate. DISCUSSION: These issues discussed
      are: (1) The shifting sands of methodological orthodoxy - the historical context
      in which audit trails emerged. (2) The individual construction of logic. (3)
      'Grounded in the data' or 'going beyond the words'- the key differences between
      descriptive and interpretive findings. (4) The singular relationship between
      qualitative researcher and their data. (5) The growing acknowledgement that
      method alone is insufficient. (6) The challenging example of visionaries.
      CONCLUSION: We argue that using audit trails as a means to achieve confirmability
      of qualitative research findings is an exaggeration of the case for method, and
      may do little to establish the credibility of the findings. We also introduce a
      preliminary case for testing the credibility of theory induced by expert
      qualitative researchers, in part by means of its usefulness; its 'fit and grab',
      rather than by the researcher's adherence to contemporary methodological
      orthodoxy. In other words, the absence of audit trails does not necessarily
      challenge the credibility of qualitative findings, particularly if an expert
      qualitative researcher produced the findings.

PMID- 14705998
TI  - Using student nurses as teachers in inquiry-based learning.
AB  - BACKGROUND: Traditionally, teaching in nurse education colleges and universities
      in the United Kingdom (UK) has relied substantially on didactic, large group,
      teacher-led approaches. Emerging literature identifies a shift towards student
      centred learning in a variety of formats, such as problem- and enquiry-based
      learning. These approaches require students to take greater responsibility for
      both their own learning and that of others. Internationally, and in a number of
      academic educational disciplines, use of peer-assisted learning, supplemental
      instruction and peer tutoring as curriculum initiatives has aided improvement in
      student retention and academic performance. There is, however, a paucity of
      literature exploring the use of undergraduate student nurses as peer teachers.
      AIM: To explore the viability of using student nurses as teachers in an inquiry
      based nursing curriculum and to ascertain the value students place on this
      teaching and learning method. METHOD: The first phase of the study involved
      observation of 'parallel resource sessions': teacher-led sessions that addressed
      a theoretical component of the curriculum. In the second phase, student feedback
      of these sessions to their peers was observed. This was followed by focus group
      interviews (with a total of 240 participants), which were analysed using thematic
      analysis. FINDINGS: The findings suggest that student nurses were uncomfortable
      with being used as teachers, often questioned the intrinsic worth of this
      approach as a developmental tool, and considered the responsibility for teaching
      the content of parallel resource sessions to lie with nurse educators.
      CONCLUSION: Nurse educators must continue to explore innovative approaches to
      improve both student nurses' experience and their fitness for practice. The
      strategy of using student nurses as teachers may be appropriate in some
      circumstances but requires further research, considerable support and continual
      evaluation.

PMID- 14705999
TI  - Downsizing and reorganization: demands, challenges and ambiguity for registered
      nurses.
AB  - BACKGROUND: The 1990s were characterized by substantial financial cuts, and
      related staff redundancies and reorganizations in the Swedish health care sector.
      A large hospital in Sweden was selected for the study, in which downsizing had
      occurred between 1995 and 1997. The number of staff in the hospital was reduced
      by an average of 20%, and 10% were relocated to other departments. OBJECTIVE: The
      aims of this study were to explore registered nurses' experiences of psychosocial
      'stressors' and 'motivators', and how they handled their work situations,
      following a period of personnel reductions and ongoing reorganization. METHOD:
      Interviews were undertaken with 14 nurses working in one Swedish hospital. Nurses
      were interviewed in 1997 about the recent and last round of redundancies, and
      were followed up 1 year later in 1998 and again in 2001. Interviews were
      audiotaped, transcribed and analysed for thematic content. RESULTS: Five themes
      emerged in relation to nurses' perceived stressors, motivators, and coping
      options: 'distrust towards the employer', 'concurrent demands and challenges',
      'professional ambiguity, 'a wish for collaboration', and 'efforts to gain
      control'. A common feature was duality and ambiguity in nurses' descriptions of
      the phenomena studied, meaning that identified themes had underlying sub-themes
      with both negative and positive dimensions. CONCLUSIONS: The concurrence of 'ever
      growing job demands' and 'work going unrewarded' contributed to a feeling of
      being taken advantage of by the employer. The 'waste of human resources' and
      'competence drain' that followed redundancies provoked anger. Unfulfilled
      collaboration with doctors was a major stress producer, which related to both the
      downsized work organization, and the complex 'deference-dominance' doctor-nurse
      relationship. The well-being of nurses depends on being an equal/parallel health
      professional in a comprehensive team that shares knowledge and improves
      collaborative care of patients. A consciously formulated nursing philosophy
      emerged as a health-promoting resource. This study demonstrates the importance of
      analysing feelings relating to professional ambiguity and gaining influence in a
      gender-related, hierarchical environment, and the need to support professional
      assertiveness in relation to superiors and doctors. It is also important to
      stress considerations that relate to differences in the age, care philosophy, and
      psychosocial health conditions of nurses.

PMID- 14706000
TI  - Occupational health and school health: a natural alliance?
AB  - BACKGROUND: The United Kingdom National Health Service aims to provide a holistic
      'cradle to grave' service. In order to achieve this, systems are in place for
      effective communication between providers of services for babies and children.
      However, when children leave school, communication between the school health
      services and workplace health services to protect and promote the health of the
      new workforce is rare. Working together is a commonly-stated rhetoric of
      contemporary nursing theory, but often this is not applied in practice. School
      health and occupational health have similar aims and objectives and, by working
      together, may be able to improve the health of large populations for a lifetime.
      AIM: This paper aims to examine the similarities in principles and practices
      between school health and occupational health nurses, and to identify areas of
      overlap in which collaboration could improve care for clients of both services.
      DISCUSSION: The paper examines the nature of nursing in occupational and school
      settings, and similarities and differences in policy, law and principles. It also
      examines these two areas of practice within a public health framework, looking
      for areas of overlap. A basis is suggested for collaborative working between the
      two areas, and barriers, facilitators and benefits of this practice are examined.
      CONCLUSION: We conclude that there does exist a natural alliance between
      occupational and school health nursing, and that the two should work together to
      provide continuity of care for clients on leaving school, and to prepare children
      and young people for the workplace and any special health issues in their chosen
      careers.

PMID- 14706001
TI  - The description and evaluation of a longitudinal pilot study of a smoking
      relapse/reduction intervention for perinatal women.
AB  - BACKGROUND: Up to 70% of women who quit smoking while pregnant will relapse
      during the first postnatal year. In this study, a community-based, ecological
      approach guided the development and implementation of a smoking cessation
      intervention for perinatal women. AIMS: The aims of this pilot project were to:
      (1) develop and implement a community-based intervention to assist women to stop
      smoking or prevent smoking relapse during the pre- and postnatal periods, (2)
      provide feedback on participants' perceptions of the helpfulness of the
      intervention, (3) compare perceptions of the helpfulness of the intervention
      between women who received the intervention during the prenatal vs. postnatal
      periods, and (4) identify additional components of the intervention which need to
      be included in future research. DESIGN/METHODS: Using a participative process and
      a detailed review of the literature, researchers, health care professionals and
      women (pregnant or postnatal) developed a multifaceted intervention. The
      intervention included four core components, which all women received: home visit
      by the intervention nurse, follow-up telephone call(s), resource package, and
      letter of congratulations. Additional optional components included: telephone
      help line, support groups, referrals and other services. Forty-two women who were
      pregnant or had recently delivered participated. Descriptive and evaluation data
      were collected from participants using questionnaires and telephone interviews.
      The research was approved by the university Research Ethics Board. FINDINGS:
      Participants found the core components of the intervention to be helpful in their
      smoking cessation goals, particularly the home visit and resource material. The
      support groups and smoking help line were not used. There were no differences in
      how helpful the components of the intervention were perceived to be between women
      who received it in the prenatal or postnatal periods. CONCLUSIONS: Future
      research is needed to evaluate the effectiveness of the intervention.

PMID- 14706002
TI  - Fatigue in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Fatigue is a frequently occurring symptom in patients with chronic
      obstructive pulmonary disease (COPD). Despite this, relatively few studies have
      objectively assessed patients' perceptions of fatigue and the impact of perceived
      fatigue on their everyday lives. OBJECTIVE: The purpose of this study was to
      describe the prevalence, duration and severity of fatigue among patients with
      COPD and the impact of perceived fatigue on cognitive, physical and psychosocial
      functioning in comparison with controls. METHOD: The Fatigue Impact Scale,
      including physical, psychosocial and cognitive dimension and structured questions
      about the frequency, duration, and severity of fatigue was mailed to 44
      outpatients with COPD and 88 randomly selected age- and sex-matched controls. In
      total 36 patients and 37 controls completed the questionnaire. RESULTS: Almost
      half of the patients (47.2%), reported fatigue every day during the preceding
      month compared with 13.5% of the control group (P < 0.001). The duration of
      fatigue was more than 6 hours in 52.7% of the patients and 44.4% reported that
      fatigue was either the worst or one of the worst symptoms they had, compared with
      18.9% (P < 0.001) and 10.8% (P < 0.01) in the control group. The patients
      reported a significantly greater impact of fatigue on cognitive, physical and
      psychosocial functioning compared with the control group (P < 0.001). CONCLUSION:
      These findings indicate that fatigue is a highly prevalent symptom, which impacts
      on patients' functional condition and needs to be professionally assessed and
      managed.

PMID- 14706003
TI  - Barriers to evidence-based practice in primary care.
AB  - BACKGROUND: Evidence-based practice is one of the most important underlying
      principles in modern health care. In the United Kingdom, successive governments
      have highlighted the fact that a quality health service is built upon the use of
      best evidence. Health professionals are becoming more accountable within clinical
      governance structures for the care they provide. The need to use robust research
      findings effectively is a critical component of their role. However, studies show
      that a number of barriers prevent the effective use of best available evidence.
      AIM: This study aimed to identify barriers to evidence-based practice in primary
      care. METHOD: A specially designed questionnaire was used to gather respondents'
      perceptions of the barriers to evidence-based practice. Data were collected in
      2000/2001. FINDINGS: Findings show that general practitioners (GPs) ranked
      barriers differently to community nurses. GPs believed that the most significant
      barriers to using evidence in practice were: the limited relevance of research to
      practice, keeping up with all the current changes in primary care, and the
      ability to search for evidence-based information. In contrast, the most
      significant barriers to the identified by community nurses were poor computer
      facilities, poor patient compliance and difficulties in influencing changes
      within primary care. This suggests that these two groups may require different
      strategies for barrier removal. CONCLUSIONS: Identifying barriers is just the
      first step to addressing issues surrounding the use of evidence-based practice.
      Extra resources will be needed if these barriers are to be tackled. However, if
      the resultant change improves the health and wellbeing of people and communities,
      then the extra costs would be offset by more efficient use of services.

PMID- 14706004
TI  - Leisure time activity of Mexican Americans with diabetes.
AB  - BACKGROUND: Diabetes is a worldwide health problem with increasing prevalence,
      particularly among ethnic minorities. Activity is a major component of diabetes
      management that can help to prevent the deadly complications of the disease.
      Assessment of the activities in which individuals with diabetes from specific
      ethnic groups such as Mexican Americans engage may facilitate identification of
      strategies to encourage activity among those who do not participate in activity
      or have only minimal, sporadic participation. AIMS: The aims of this research
      were to determine: (1) What proportion of Mexican Americans with diabetes do and
      do not exercise? (2) What are the preferred types of leisure time activity by
      gender and age? (3) What the relationship is between leisure time activity and
      treatment of diabetes? METHODS AND INSTRUMENT: A secondary analysis of data from
      the third National Health and Nutrition Examination Survey (NHANES) (1988-1994)
      was conducted to explore leisure time activities of self-identified Mexican
      Americans with diabetes. RESULTS: Mexican American adults in this study indicated
      gardening (33.7%) and walking (31.5%) as the leisure time activities in which
      they engaged most frequently in the month preceding data collection. Gardening
      and walking were frequent leisure activities of study participants for all
      categories of pharmacological management of the diabetes. Many did not
      participate in any leisure time activity in the month preceding data collection.
      Only six of every 10 Mexican Americans (61%) with diabetes exercised. Males (n =
      136; 71%) were more likely to engage in physical activity than females (n = 171;
      54%). LIMITATIONS: Only leisure time activity was assessed; occupational activity
      and household activity were not included. Data were based on self-report rather
      than an objective measure of subject activity. Subject knowledge of the need for
      activity as a component of diabetes management was not assessed and may not be
      recognized as an integral part of care. CONCLUSIONS: Diabetes is a significant
      health problem for many ethnic groups, including the Mexican American population,
      and regular physical activity is a critical component of disease management.
      Facilitating activity in this ethnic group is integral to controlling
      complications of this chronic disease.

PMID- 14706005
TI  - Teamworking in nursing homes.
AB  - BACKGROUND: Nursing homes have an important role in the care of frail older
      people, but concerns have been raised about the quality of care. High standards
      of care appear to be facilitated when nurses work in effective teams. Greater
      understanding of teamworking in nursing homes could have implications for
      training and policy-making. AIM: The aim of the study was to explore the
      experiences and perceptions of teamworking with qualified nurses working in
      nursing homes. METHOD: This was a small, exploratory focus group study. The
      sample was 12 qualified nurses working in nursing homes in the south of England.
      Transcriptions of the focus groups were coded by the research team and agreement
      was achieved by discussion. FINDINGS: Teams described were constructed in
      'vertical', hierarchical terms rather than as 'flat', collaborative structures.
      The achievement of good teamworking was hindered by inadequate communication,
      particularly as many staff worked part-time and on shifts. Management was
      perceived as remote, and lines of authority were ambiguous and unfocused.
      CONCLUSIONS: This group of nurses were aware of the difficulties of working in a
      hierarchical, profit-making culture. Individually, they tried to provide good
      quality care for patients and aspired to teamworking, but seldom succeeded to
      their satisfaction. There may be considerable potential to improve the working
      lives of staff and quality of patient care by effective teamworking. However,
      significant barriers, particularly concerning organizational culture, need to be
      overcome.

PMID- 14706006
TI  - Fatigue, psychological distress, coping and quality of life in patients with
      uterine cancer.
AB  - BACKGROUND: Cancer-related fatigue (CRF) is a subjectively experienced symptom
      that is multidimensional and multifactorial. Patients with cancer have identified
      fatigue as one of the major troubling symptoms and the primary cause of distress
      in their lives. AIMS: The major aim of the study was to examine how patients
      diagnosed with uterine cancer describe their experience of fatigue, psychological
      distress, coping resources and quality of life. A secondary aim was to describe
      the relationship between selected variables. METHOD: A descriptive and
      correlational design was used and the study was conducted at a university
      hospital in Sweden. The study population consisted of women, diagnosed with
      uterine cancer, who where scheduled to receive curative external radiation
      therapy. Sixty women participated in the study and data were collected through
      self-report instruments. Demographic and clinical data were extracted from
      patient records. The data were collected during year 2000-2002. The Conceptual
      Model of Symptom Management was used as a framework to guide the study. FINDINGS:
      Patients experienced a low grade of fatigue and psychological distress, but their
      functional status and global quality of life was high. Significant correlations
      were found between general fatigue and anxiety and also between general fatigue
      and depression. There was a significant negative correlation between general
      fatigue and coping resources. Depression explained 44% of the variance in general
      fatigue. CONCLUSIONS: The findings provide knowledge about predictors of CRF in
      women with uterine cancer, and can serve as a basis for future longitudinal
      studies in which different prophylactic strategies against therapy-related
      fatigue are prospectively studied.

PMID- 14706007
TI  - Estimating core temperature in infants and children after cardiac surgery: a
      comparison of six methods.
AB  - BACKGROUND: Monitoring temperature in critically ill children is an important
      component of care, yet the accuracy of methods is often questioned. Temperature
      measured in the pulmonary artery is considered the 'gold standard', but this
      route is unsuitable for the majority of patients. An accurate, reliable and less
      invasive method is, however, yet to be established in paediatric intensive care
      work. AIM: To determine which site most closely reflects core temperature in
      babies and children following cardiac surgery, by comparing pulmonary artery
      temperature to the temperature measured at rectal, bladder, nasopharyngeal,
      axillary and tympanic sites. METHOD: A convenience sample of 19 postoperative
      cardiac patients was studied. INTERVENTIONS: Temperature was recorded as a
      continuous measurement from pulmonary artery, rectal, nasopharyngeal and bladder
      sites. Axillary and tympanic temperatures were recorded at 30 minute intervals
      for 6 1/2 hours postoperatively. STUDY LIMITATIONS: The small sample size of 19
      infants and children limits the generalizability of the study. RESULTS: Repeated
      measures analysis of variance demonstrated no significant difference between
      pulmonary artery and bladder temperatures, and pulmonary artery and
      nasopharyngeal temperatures. Intraclass correlation showed that agreement was
      greatest between pulmonary artery temperature and temperature measured by bladder
      catheter. There was a significant difference between pulmonary artery temperature
      and temperature measured at rectal, tympanic and pulmonary artery and axillary
      sites. Repeated measures analysis showed a significant lag between pulmonary
      artery and rectal temperature of between 0 and 150 minutes after the 6-hour
      measurement period. CONCLUSIONS: In this study, bladder temperature was shown to
      be the best estimate of pulmonary artery temperature, closely followed by the
      temperature measured by nasopharyngeal probe. The results support the use of
      bladder or nasopharyngeal catheters to monitor temperature in critically ill
      children after cardiac surgery.

PMID- 14706008
TI  - Characteristics of image-detected solid renal masses: implication for optimal
      treatment.
AB  - BACKGROUND: Solid renal masses are found increasingly. Further analysis of the
      characteristics of solid renal masses is useful for optimal treatment. METHODS: A
      retrospective analysis of all solid renal masses was conducted from December 1998
      to May 2003 at the Urology Department, Central University Hospital of Saint
      Etienne, France. A total of 162 solid renal masses were treated. The preoperative
      imaging diagnosis of ultrasound and computed tomography, and final pathological
      results were reviewed. RESULTS: One hundred and forty-five tumors were
      pathologically confirmed to be renal cell carcinomas (RCC); 17 tumors (10.5%)
      were benign. There were eight renal oncocytomas, eight renal angiomyolipomas and
      one benign mixed epithelial/stroma tumor. Three oncocytomas and five
      angiomyolipomas were strongly suspected before surgery. The majority of the
      benign tumors were < or =4 cm. The percentage of small benign tumors (< or =4 cm)
      was significantly higher than large benign tumors (>4 cm). Although it is
      possible to use imaging to detect some benign tumors, the majority of benign
      tumors cannot be diagnosed definitively by imaging before surgery. CONCLUSIONS:
      Malignancy in solid renal masses is tumor-size related. Benign solid renal tumors
      appear mainly as small-sized tumors. The preoperative differentiation between an
      RCC and a benign tumor can be difficult. Our data suggest that a biopsy is
      necessary in selected patients to achieve the maximum accuracy in order to
      provide optimal treatment.

PMID- 14706009
TI  - Low-grade renal epithelial tumor originating from the distal nephron.
AB  - There are few published reports of low-grade renal epithelial tumor originating
      from the distal nephron. However, it should not be disregarded clinically,
      because the actual number of patients with such tumors may be higher than
      expected. We investigated the immunohistochemical profile of a histologically
      distinct subtype of such a tumor in detail, in addition to the clinical course
      and imaging studies. The present study demonstrated that both glandular and
      spindle cell components of this tumor have a persistent characteristic of an
      epithelial tumor arising from the distal tubule or collecting duct. This tumor is
      a benign complex neoplasm that can be treated successfully with radical surgery.
      Beta-catenin and E-cadherin are suggested to play a crucial role in tumorigenesis
      and the biphasic arrangement of this neoplasm, concerning the expression of
      epithelial membrane antigen and carbohydrate antigen 19-9. We suggest that the
      term 'distal nephron epithelioma' is appropriate for classifying such rare but
      clinicopathologically distinct tumors.

PMID- 14706010
TI  - Decreased expression of KAI1 metastasis suppressor gene is a recurrence predictor
      in primary pTa and pT1 urothelial bladder carcinoma.
AB  - OBJECTIVE: To examine the expression of the KAI1 metastasis suppressor gene and
      to evaluate its relationship with tumor recurrence in primary pTa and pT1
      urothelial bladder carcinoma. METHODS: Samples were obtained from 87 patients
      after transurethral resection (TUR). Tumor stage and grade were reviewed in 33
      patients with pTa and in 54 patients with pT1, with a mean follow-up time of 47.4
      +/- 30.1 months. The KAI1 protein immunohistochemical assay was performed.
      Prognosis was analyzed using the Kaplan-Meier method and Cox's proportional
      hazards model. Correlation between KAI1 expression and recurrence according to
      each clinicopathological factor was comparatively evaluated using the chi-squared
      test. RESULTS: Decreased expression of KAI1 protein failed to reach statistical
      significance for stage (P = 0.25) or morphology of tumor stem (P = 0.19), but it
      was significantly related to tumor size (P = 0.016). The recurrence-free 5-year
      survival rates of the group with decreased KAI1 expression was 69.7%, which was
      significantly higher than the 22.2% for the KAI1-positive group (P < 0.0001). In
      univariate and multivariate analyses, decreased expression of KAI1 protein, stage
      pT1, tumor size >3 cm and sessile tumors were independent prognosis factors of
      recurrence. Despite the lower recurrence rate expected by considering only the
      clinicopathological factors, decreased KAI1 expression was able to identify the
      group with a high risk of recurrence. CONCLUSIONS: Downregulated KAI1 expression
      in bladder tumors tends to relate to stage and morphology of the tumor stem and
      was significantly correlated to tumor size. Decreased expression of KAI1 was
      associated with the degree of invasiveness and progression of the cancer and was
      an independent prognostic factor of recurrence in primary pTa and pT1 urothelial
      bladder carcinoma.

PMID- 14706011
TI  - Significance of renal function in changes in acid-base metabolism after
      orthotopic bladder replacement: colon neobladder compared with ileal neobladder.
AB  - BACKGROUND: The objective of this study was to determine whether renal function
      influences the acid-base metabolism in patients undergoing orthotopic bladder
      replacement using intestinal segment. METHODS: Acid-base balance, serum
      electrolytes and renal function were studied in 30 patients with colon neobladder
      and 18 patients with ileal neobladder. Mean follow up was 51 months. Effects of
      renal function on acid-base metabolism in both types of bladder replacement were
      compared. Therapeutic efficacy of the sodium bicarbonate administration was also
      evaluated in cases with hyperchloremic acidosis. RESULTS: No significant
      differences were observed in any of the variables examined between the colon and
      ileal neobladder groups, except for potassium concentration. Although metabolic
      acidosis was detected using the Siggard-Anderson acid-base nomogram in eight
      (26.7%) and seven (38.9%) patients in the colon and ileal neobladder groups,
      respectively, this difference was not significant. In both the colon and ileal
      neobladder groups, the serum creatinine concentrations in patients diagnosed with
      metabolic acidosis were significantly higher than in those diagnosed with a
      normal metabolic status. Furthermore, as a result of severe metabolic acidosis,
      three (10.0%) and three (16.7%) patients in the colon and ileal neobladder
      groups, respectively, were administered sodium bicarbonate and their metabolic
      status was fully normalized. CONCLUSIONS: Despite there being no statistical
      difference, patients with ileal neobladder may more easily develop metabolic
      acidosis compared with those with colon neobladder. In addition, a close
      association between the serum creatinine level and the degree of metabolic
      acidosis was observed in both groups. However, even if severe metabolic acidosis
      occurs, it is relatively easy to correct using sodium bicarbonate. These findings
      suggest that it might be safe to use a colon segment for orthotopic bladder
      reconstruction in patients with higher serum creatinine levels, despite no
      significant difference in acid-base metabolism and detection rates of metabolic
      acidosis between the colon and ileal neobladder groups.

PMID- 14706012
TI  - Combination of a cholinergic drug and an alpha-blocker is more effective than
      monotherapy for the treatment of voiding difficulty in patients with underactive
      detrusor.
AB  - AIM: The aim of the present study was to compare the effectiveness of a
      cholinergic drug, an alpha-blocker and combinations of the two for the treatment
      of underactive detrusor. METHODS: One hundred and nineteen patients with
      underactive bladder were assigned to three groups: the cholinergic group,
      consisting of 40 patients taking bethanechol chloride (60 mg/day) or distigmine
      bromide (15 mg/day); the alpha-blocker group, consisting of 38 patients taking
      urapidil (60 mg/day); and the combination group, consisting of 41 patients taking
      both a cholinergic drug and an alpha-blocker. The effectiveness of each therapy
      was assessed 4 weeks after initialization of the therapy. RESULTS: Total urinary
      symptom scores (International Prostate Symptom Score, IPSS) remained unchanged
      after the cholinergic therapy, but were significantly lower after the alpha
      blocker treatment (P = 0.0001) and the combination therapy (P = 0.0001). With
      regard to the total IPSS, there were significant differences between the
      cholinergic and the alpha-blocker groups (P = 0.0008), and also between the
      cholinergic and combination groups (P = 0.0033), in favor of the latter. The
      average and maximum flow rates did not increase significantly after monotherapy
      with either the cholinergic drug or the alpha-blocker, but they significantly
      increased after combination therapy compared to baseline values (P = 0.0033 and
      P= 0.0004, respectively). Postvoid residual volume did not decrease significantly
      after the cholinergic drug therapy, but decreased significantly after the alpha
      blocker (P = 0.0043) and the combination therapies (P = 0.0008). The percentage
      of residual urine decreased significantly after therapy in all groups (P =
      0.0005, P= 0.0176 and P= 0.0001, respectively). CONCLUSION: Combination therapy
      with a cholinergic drug and an alpha-blocker appears to be more useful than
      monotherapy for the treatment of underactive detrusor.

PMID- 14706013
TI  - Therapeutic effect of transurethral needle ablation in non-bacterial prostatitis:
      chronic pelvic pain syndrome type IIIa.
AB  - AIM: Non-bacterial prostatitis is difficult to manage with conventional
      treatment. This study was undertaken to evaluate the therapeutic effect of
      transurethral needle ablation (TUNA) on men with chronic inflammatory non
      bacterial prostatitis. METHODS: Thirty-two patients with non-bacterial
      prostatitis (type IIIa) were treated with TUNA. The TUNA procedure, which uses
      radiofrequency energy, heats the prostate tissue to approximately 90-110 degrees
      C over a 5-min period. Evaluation consisted of a prostatitis symptom severity
      score chart, the monitoring of the leukocyte count in the expressed prostatic
      secretion (EPS) and a subjective global assessment. RESULTS: The decrease in the
      prostate symptom severity score chart at 3 and 6 months compared with the
      baseline assessment was statistically significant. Analysis of the leukocyte
      levels in the EPS in 14 patients was available. All 14 patients had a decrease in
      the EPS leukocyte count 3 months after treatment. However, six of these men (43%)
      still had EPS leukocyte levels above the normal indices (>10 white blood cells
      per high-power field). A second session of TUNA on these partial responders
      resulted in three of the six men obtaining a normal EPS leukocyte count. At 6
      months following treatment, complete, partial and poor improvement in terms of
      subjective global assessment were noted in 60, 35 and 5% of patients,
      respectively. No major complications, including those of sexual dysfunction or
      retrograde ejaculation, were noted in this cohort. CONCLUSIONS: Transurethral
      needle ablation appears to be an easy, safe and effective treatment for men with
      chronic inflammatory non-bacterial prostatitis.

PMID- 14706014
TI  - Chemohormonal therapy as primary treatment for metastatic prostate cancer: a
      randomized study of estramustine phosphate plus luteinizing hormone-releasing
      hormone agonist versus flutamide plus luteinizing hormone-releasing hormone
      agonist.
AB  - BACKGROUND: The present study was undertaken mainly to investigate whether
      chemohormonal therapy with estramustine phosphate plus luteinizing hormone
      releasing hormone (LHRH) agonist has a more beneficial effect than the hormonal
      therapy with flutamide plus LHRH agonist for newly diagnosed patients with
      metastatic prostate cancer. METHODS: A total of 57 patients with metastatic
      prostate cancer aged 59-80 years (median 74 years) were entered in the study and
      were randomized to the treatment of estramustine phosphate (560 mg/day) plus LHRH
      agonist (estramustine group) or flutamide (375 mg/day) plus LHRH agonist
      (flutamide group) with stratification for the degree of performance status,
      histological differentiation and bone metastasis. RESULTS: Both of the treatment
      regimens were well tolerated with similar incidences of adverse drug reactions.
      The overall response rates (complete response plus partial response) at 12 weeks
      after treatment in the estramustine and flutamide groups were 76 and 55%,
      respectively. The median time to objective progression for the estramustine group
      (25.4 months) was longer than that of the flutamide group (14.6 months). The
      serum levels of follicle stimulating hormone and testosterone were significantly
      lower in the estramustine group. CONCLUSIONS: Chemohormonal therapy with
      estramustine phosphate plus LHRH agonist showed longer clinical progression-free
      survival than the hormonal therapy with flutamide plus LHRH agonist (P = 0.03),
      although there was no significant difference in the overall survival. A larger
      scaled trial with more statistical power is required to clarify that the former
      regimen is more beneficial than the latter for newly diagnosed patients with
      advanced prostate cancer.

PMID- 14706015
TI  - Small renal oncocytoma with central cystic degeneration.
AB  - A case of a small renal oncocytoma with central cystic degeneration, 15 mm in
      diameter, is reported. Contrast-enhanced computed tomography showed the tumor
      contained a central hypoattenuating region and had an irregular, heterogeneously
      enhanced wall. Magnetic resonance images showed a well-circumscribed lesion and
      the T(1)-weighted image indicated medium signal intensity, whereas the T(2)
      weighted image indicated slight hypointensity. Both T(1)- and T(2)-weighted
      images showed central hyperintensity. Our preoperative diagnosis was renal cell
      carcinoma originating in a renal cyst wall or cystic renal cell carcinoma.
      Nephrectomy was performed because frozen-section examination did not completely
      rule out malignancy. The final pathological diagnosis of the entire surgical
      specimen was renal oncocytoma with cystic degeneration. To our knowledge, this is
      the 14th case of renal oncocytoma with central cystic degeneration reported in
      the published works. We discuss herein the variant forms of oncocytoma and
      difficulties with their preoperative diagnosis, especially when the tumor is
      small.

PMID- 14706016
TI  - Successful recovery from a massive pulmonary artery tumor embolism occurring
      during surgery for renal cell carcinoma.
AB  - We report herein on a case of renal cell carcinoma with retrohepatic inferior
      vena cava tumor thrombus in which intraoperative cardiac arrest from a massive
      pulmonary embolism was managed successfully with emergency sternotomy and
      cardiopulmonary bypass, followed by the removal of the primary site and pulmonary
      artery embolus.

PMID- 14706017
TI  - Case of alpha-fetoprotein-producing transitional cell carcinoma of the renal
      pelvis.
AB  - An alpha-fetoprotein-producing transitional cell carcinoma of the renal pelvis is
      extremely rare. To our knowledge, this has not been reported previously. We
      present the first case of an alpha-fetoprotein-producing transitional cell
      carcinoma of the renal pelvis in a 70-year-old female.

PMID- 14706018
TI  - Renal silica calculi in an infant.
AB  - We report on a rare case of urinary silica calculi in a 10-month-old boy. The boy
      showed acute pyelonephritis with left hydronephrosis. Ultrasonography and
      computed tomography revealed a calculus at the left ureteropelvic junction and
      three additional calculi in the left renal pelvis. Because his acute
      pyelonephritis was refractory to conventional chemotherapy, the patient underwent
      successful left percutaneous nephrostomy followed by percutaneous
      nephrolithotripsy for the renal calculi. All stones disappeared and his
      postoperative course was uneventful. On infrared spectrophotometry, the
      wavelength pattern of the stones exhibited two peaks at 1100 and 1650 cm(-1),
      consistent with the determination that the calculi consisted of a mixture of
      silicate (78%) and calcium oxalate (22%). We consider that the etiology of the
      calculi in this child can be ascribed to the silicate-rich water used to dilute
      milk. In Japan, 46 adult patients with urinary silicate calculi have been
      reported in the literature; however, there is no report of the disease in an
      infant in Japan.

PMID- 14706019
TI  - Case of leiomyosarcoma of the renal pelvis.
AB  - A 54-year-old man presented at the Mibayashi clinic with bowel discomfort.
      Ultrasonography showed a left renal mass and the patient was referred to Noto
      General Hospital for urological evaluation. Results of the physical examination
      were unremarkable, but computed tomography and magnetic resonance imaging
      demonstrated a large tumor in the middle of the left kidney. The patient
      underwent left nephrectomy. On hemisection of the kidney, a firm tumor, measuring
      8 x 7.5 cm, was seen occupying the renal pelvis. The histological diagnosis was
      leiomyosarcoma arising from the right renal pelvis. No treatment was provided
      after surgery and no recurrence was observed 6 months postoperatively.

PMID- 14706020
TI  - New phenotype of accessory scrotum with perineal lipoblastoma: coexistence of
      midperineal and lateral accessory scrotums.
AB  - We present the extremely rare phenotype of an accessory scrotum with an
      associated lipoblastoma. There was a coexistence of midperineal and lateral
      types. To our knowledge, this phenotype has never been reported. The
      lipoblastoma, which arose in the perineum, divided the moving labioscrotal
      swelling into three parts during early fetal life. This resulted in the specific
      anomaly in this patient.

PMID- 14706022
TI  - Propofol intravenous conscious sedation for anxious children in a specialist
      paediatric dentistry unit.
AB  - OBJECTIVES: To report on both the use and dosage of propofol, as a new
      intravenous (IV) conscious sedative agent, for anxious children referred to a
      specialist paediatric dentistry service. SETTING: Paediatric Dentistry Unit,
      Glasgow Dental Hospital and School. SAMPLE: Thirty-four children, 25 females and
      9 males, mean age 12 years 10 months, with a mean weight of 54.6 kg (range 30-110
      kg). METHODS: Report from 34 patients receiving intravenous sedation for the
      first time in respect of weight dose and amount of treatment completed. RESULTS:
      Thirty-two children successfully accepted operative dental care on their first
      visit, they received a mean total dose of 146.25 mg of propofol (range 10 mg to
      356 mg); in relation to body weight, the mean was 2.5 mg/kg (range 0.2-5.4
      mg/kg). The treatment that they received included fissure sealants, amalgam and
      adhesive restorations, root canal therapy and single and multiple extractions.
      Their sedation and recovery were uneventful. CONCLUSIONS: Sub-anaesthetic doses
      of propofol used for IV conscious sedation infusion facilitated operative dental
      treatment in anxious children.

PMID- 14706023
TI  - Morbidity following dental treatment of children under intubation general
      anaesthesia in a day-stay unit.
AB  - OBJECTIVES: To determine which variables were best related to the overall
      morbidity of a child undergoing dental general anaesthetic (GA) and then to use
      these variables to determine those factors that might influence the extent and
      severity of morbidity experienced by healthy children following dental GA. SAMPLE
      AND METHODS: Data were collected on anxiety, pain and morbidity, GA procedure and
      dental procedure from 121 children attending a day stay GA unit for dental
      treatment. Patients were interviewed preoperatively, postoperatively before
      discharge then four further times over the next 148 h. Data were analysed using
      multivariate regression. RESULTS: Thirty-one per cent of subjects had restorative
      work, 60% had at least one tooth extracted, 54% had a surgical procedure. Use of
      local analgesia reduced postoperative pain whilst an increase in the number of
      surgical procedures increased it. Increase in anaesthetic time was related to
      increased odds of feeling sleepy and nauseous, females were more likely to
      complain of sleepiness or weakness. Feelings of dizziness were increased if the
      patient was given local analgesia during the procedure. CONCLUSIONS: Pain
      following dental GA was the most prevalent and long lasting symptom of
      postoperative morbidity in this study. Reductions in operating time and
      improvement in pain control have the potential to reduce reported morbidity
      following dental GA.

PMID- 14706024
TI  - Factors related to severe untreated tooth decay in rural adolescents: a case
      control study for public health planning.
AB  - OBJECTIVES: In this case-control study of rural adolescents we identified factors
      to discriminate those who have high levels of tooth decay and receive treatment
      from those with similar levels who receive no treatment. METHODS: The sample was
      drawn from all 12-20-year-olds (n = 439) in a rural high school in Washington
      State, U.S. The criterion for being included was 5 or more decayed, missing or
      filled teeth. The questionnaire included structure, history, cognition and
      expectation variables based on a model by Grembowski, Andersen and Chen. RESULTS:
      No structural variable was related to the dependent variable. Two of 10 history
      variables were related: perceived poor own dental health and perceived poor
      mother's dental health. Four of eight cognition variables were also predictive:
      negative beliefs about the dentist, not planning to go to a dentist even if
      having severe problems, not being in any club or playing on a sports team and not
      having a best friend. No relationship was found for the expectation variable
      'usual source of care'. CONCLUSIONS: These data are consistent with the
      hypothesis that untreated tooth decay is associated with avoidance of care and
      point to the importance of history and cognition variables in planning efforts to
      improve oral health of rural adolescents.

PMID- 14706025
TI  - Dental treatment needs of children in a rural subcounty of Uganda.
AB  - OBJECTIVES: To describe normative dental treatment needs of 5-7 and 12-year-olds
      in a rural sub county of Uganda and devise a strategy to improve oral health.
      DESIGN: Clinical survey. SETTING: Primary schools in the subcounty. SAMPLE AND
      METHODS: School-based random cluster sample of 236 5-7-year-olds and 202 12-year
      olds. Dental status and treatment need data were collected according to WHO Oral
      Health Surveys Basic Methods. Additional data for 12-year-olds included dental
      fluorosis using the Thylstrup and Fejerskov index (TFI), oral hygiene procedures
      and experience of oral pain in the previous month. RESULTS: In the 5-7-year-olds,
      mean dmft was 1.47 (50.8% dmft = 0). A total of 52.5% needed fillings and almost
      one third needed a tooth extracted. Among the 12-year-olds, mean DMFT was 0.64
      (65.8% DMFT = 0), 28.5% had dental fluorosis and 6.7% had TFI > 2. Toothache in
      the previous four weeks was reported by 36.5%, 30.2% needed a filling and 6.4%
      needed one or more teeth extracted. CONCLUSIONS: Dental disease is a significant
      public health problem in this population. An efficient way to meet the needs of
      the children would be to increase the availability of fluoride toothpaste and to
      develop a service to provide treatment using Atraumatic Restorative Technique.

PMID- 14706026
TI  - Caries prevalence and severity in urban Fijian school children.
AB  - OBJECTIVES: To determine the prevalence and severity of dental caries in a sample
      of urban Fijian school children. DESIGN: Cross-sectional. SAMPLE AND METHODS:
      Children aged between 6 and 8 years who attended one of four primary schools in
      different localities of Suva completed self-report questionnaires and were
      examined for dental caries. RESULTS: A total of 704 children (response rate =
      72.4%) returned questionnaires and were examined dentally. The prevalence of
      dental caries in the primary dentition was 87.6% and in the permanent dentition,
      46.7%. The mean dfs and mean DFS were 8.43 (SD 7.82) and 2.38 (SD 1.37),
      respectively. High caries prevalence and severity were associated with infrequent
      brushing, snacking on sugar-containing foods, having seen a dentist before, and
      having last visited a dentist because of pain. CONCLUSIONS: The caries prevalence
      of the sample was comparable with findings from a national oral health survey
      conducted in 1985/86, but the caries severity was greater. As in other developing
      countries, this may be due to an increased availability of refined sugar products
      without a concurrent rise in oral health awareness. The study findings contribute
      to the overall picture of Fijian school children's dental health.

PMID- 14706027
TI  - Detection of a highly toxic clone of Actinobacillus actinomycetemcomitans (JP2)
      in a Moroccan immigrant family with multiple cases of localized aggressive
      periodontitis.
AB  - The JP2 clone of Actinobacillus actinomycetemcomitans, a high-leukotoxin
      producing strain, characterized by a 530-basepair (bp) deletion in the promoter
      region of the leukotoxin gene operon and mainly found among individuals with
      African origin, is associated with localized aggressive periodontitis. The
      objective of the study was to examine the occurrence of periodontal disease in a
      Moroccan immigrant family living in Denmark in which the oldest son (14 year) was
      referred and treated for localized aggressive periodontitis. Further, the
      potential occurrence of the JP2 clone of A. actinomycetemcomitans in the family
      was examined. Here we present the clinical, radiographic, and microbiological
      findings from the family. Clinical and radiographic examination of the other
      family members revealed that 3 of 5 younger siblings had localized aggressive
      periodontitis, one had gingivitis and the mother had chronic periodontitis.
      Despite scaling followed by intensive maintenance therapy several family members,
      including the sibling with gingivitis, had further attachment loss at the 1-year
      examination. The JP2 clone of A. actinomycetemcomitans was isolated from
      subgingival plaque samples from 4 children with periodontitis. In contrast, it
      was not detected in plaque from the oldest boy, who had been treated for
      localized aggressive periodontitis by surgery combined with antibiotic therapy.
      The 4 children with periodontitis and colonized with the JP2 clone were treated
      by scaling and antibiotic administration. One month later the JP2 clone could
      still be detected in plaque samples. In conclusion, it is confirmed that members
      of immigrant families with African origin are potential carriers of the JP2 clone
      and that those families often have multiple family members with localized
      aggressive periodontitis. It is proposed that those families are given
      periodontal examination frequently to benefit from early diagnosis and treatment
      of the disease.

PMID- 14706028
TI  - Early craniofacial signs of cleidocranial dysplasia.
AB  - OBJECTIVES: Early diagnosis of CCD is essential for a timely introduction of the
      appropriate treatment approach. Since certain symptoms first fully manifest only
      during the pubertal growth spurt, their indicatory signs are often overlooked.
      The aim of this study is to describe the initial craniofacial findings in
      patients with CCD in order to categorise their reliability for early detection.
      METHOD: 14 patients with CCD between the ages of 6 and 11 years who were referred
      to the University of Regensburg over a 4-year period were included in this study.
      The patients were examined clinically and radiologically and their dental status
      was determined. Typical signs of CCD were analysed according to such classic
      criteria as the 'quatermoon'-physiognomy described in the literature. The
      clinical findings were compared to medical data and case history. RESULTS: Early
      signs were registered for each patient. While some signs could be found in all
      patients, others were variably expressed. The typical extraoral symptoms were
      only rarely exhibited in our patient population. CONCLUSION: As various
      indicators of CCD are age related, their expression should be taken into account
      for early diagnosis. Apparent signs only manifest during the growth spurt when
      the ideal timeframe for beginning treatment has already past. The symptoms
      described should serve as early markers to aid the general and paediatric dentist
      in planning appropriate treatment or referring patients to specialised centres.

PMID- 14706029
TI  - Osteosarcoma of the jaws in children.
AB  - Two cases of osteosarcoma of the jaws in children are reported. One patient was a
      13-year-old girl whose first symptoms included nasal and maxillary sinus
      congestion, followed by epistaxis. She was found to have chondroblastic
      osteosarcoma extending through the left maxillary alveolar process and sinus.
      Following surgery and chemotherapy, the patient has been free of disease for 7
      years. The second patient, an 8-year-old boy, was diagnosed with juxtacortical
      (parosteal) osteosarcoma of the mandible, which is a less aggressive variant of
      the neoplasm. It is believed that this is the youngest patient reported to date
      with juxtacortical osteosarcoma of the jaws. He was treated by block resection of
      the right side of the mandible and is free of disease 3(1/2) years later.

PMID- 14706030
TI  - Variations in expression of oral-facial-digital syndrome (type I): report of two
      cases.
AB  - Two case reports are presented, both clearly demonstrating the diagnosis of oral
      facial-digital syndrome, type I, but widely different in the expression of the
      condition. The first patient showed only mild expression of the syndrome. On
      examination at the age of 4 years there were no obvious extra oral signs,
      intraoral findings included the presence of supernumeraries in the primary
      dentition, spacing in two areas and the presence of an extra frenum. The second
      can be considered as a more severe case. This patient had many of the typical
      manifestations, including frontal bossing, a degree of zygomatic hypoplasia and
      clinodactyly. Orally, the most striking finding was a bilateral cleft palate
      which had not been diagnosed prior to examination at the age of 6 years. Other
      findings included multiple frena and a bifid tongue.

PMID- 14706031
TI  - Surviving male with incontinentia pigmenti: a case report.
AB  - Incontinentia pigmenti, or Block-Sulzberger Syndrome, is an X-linked dominant
      disorder with characteristic skin, hair, eye and tooth abnormalities. It is
      classically considered a male-lethal disorder with recurrent miscarriages of male
      foetuses. A few cases of surviving males with incontinentia pigmenti have been
      reported in the medical literature. This article reports the medical and dental
      findings of a boy diagnosed with incontinentia pigmenti.

PMID- 14706032
TI  - Self-inflicted orodental injury in a child with Leigh disease.
AB  - Leigh disease is an inherited progressive mitochondrial neurodegenerative disease
      that affects the neurological, respiratory and cardiovascular systems and is
      associated with retardation of the intellectual and physical development. This
      report describes the case of a 4-year-old boy with Leigh disease who presented
      with self-inflicted traumatic injury to the teeth, alveolar bone, lips and tongue
      during repeated episodes of intense orofacial spasms. Conservative management of
      the injury included repositioning the fractured alveolar bone, splinting the
      traumatized teeth and planning for a mouthguard. However, after a second incident
      of severe self-induced injury to the teeth and alveolar bone, extraction of the
      anterior teeth became inevitable to protect the child from further self
      mutilation and to allow healing of the injured tissues.

PMID- 14706033
TI  - Zimmermann-Laband syndrome with bilateral developmental cataract - a new
      association?
AB  - An unusual case of Zimmermann-Laband syndrome in a young male child with an
      unreported association of bilateral developmental cataract is presented. The
      pathognomonic triad of gingival fibromatosis, aplastic or hypoplastic distal
      phalanges with absent nails, and enlargement of soft tissues of the face were
      obvious, besides the known moderate learning disability and mild hearing loss.
      The case is discussed in the light of relevant literature. To the best of our
      knowledge, this is the first report of early developmental cataracts in
      association with the Zimmermann-Laband syndrome. Besides detection and timely
      recognition of the syndrome to allow adequate dental care, ophthalmic screening
      at periodic intervals is merited to improve the overall quality of life for these
      patients.

PMID- 14706037
TI  - Visual stimuli in daily life.
AB  - People of all ages, but especially children and adolescents, are increasingly
      exposed to visual stimuli. Typical environmental stimuli that can trigger
      epileptic seizures in susceptible persons are televisions (TVs), computers,
      videogames (VGs), discotheque lights, venetian blinds, striped walls, rolling
      stairs (escalators), striped clothing, and sunlight reflected from snow or the
      sea or interrupted by trees during a ride in a car or train. Less common stimuli
      are rotating helicopter blades, disfunctioning fluorescent lighting, welding
      lights, etc. New potentially provocative devices turn up now and then
      unexpectedly. During the last decades especially, displays have become
      increasingly dominant in many of our daily-life activities. We therefore focus
      mainly on the characteristics of artificial light and on current and future
      developments in video displays and videogames. Because VG playing has been shown
      also to have positive effects, a rating system might be developed for
      provocativeness to inform consumers about the content. It is important that
      patients with epilepsy be informed adequately about their possible visual
      sensitivity.

PMID- 14706038
TI  - Physiology of human photosensitivity.
AB  - Human epileptic photosensitivity has been studied in several ways. (a) Visual
      stimulation that resembles the stimulation normally responsible for seizures,
      such as that from televisions or videogames, both of which typically use cathode
      ray tubes in which the display is created in a flickering pattern. Such
      stimulation is often rendered yet more epileptogenic by programmes with content
      that also involves flashing or patterned material. (b) Elementary visual stimuli
      that enable inferences to be drawn concerning the physiological trigger
      mechanisms. The topographic distribution of epileptiform EEG activity in response
      to such stimuli has complemented this approach, leading to the inference that the
      trigger is cortical and requires sychronised mass action of neurons. (c) Stimuli
      that avoid paroxysmal EEG activity and permit an investigation of the
      subepileptic response to visual stimuli, using the evoked potential. This has
      revealed abnormalities in the cortical mechanisms that control the response to
      strong visual stimulation.

PMID- 14706039
TI  - Epileptic syndromes and visually induced seizures.
AB  - Seizures induced by photic (or visual) stimuli or photosensitive seizures can be
      observed in generalized or focal, idiopathic, or symptomatic epilepsies, in
      progressive neurodegenerative disorders, and even in the context of situation
      related (acute symptomatic) seizures. In addition to this "transversal" presence
      of the photosensitive trait across various epilepsy types and diseases, some
      syndromes in which all, or almost all, seizures are induced by photic stimuli
      seem to have sufficient specificity and may be considered as syndromes of pure
      reflex photosensitive epilepsy. Here we review the clinical characteristic of the
      different types of photic-induced seizures and the main epileptic syndromes that
      are characterized by visual sensitivity either as the sole manifestation or as an
      accessory feature.

PMID- 14706040
TI  - Genetics of photosensitivity (photoparoxysmal response): a review.
AB  - We present a review of phenotype-genotype correlation and the genetics of
      photosensitivity. The photoparoxysmal response in EEG (PPR) is still one of the
      best paradigms for exogenously triggered brain responses based on a genetic
      predisposition. The definition of the PPR phenotype requires multiple, precise
      methodologic guidelines. Individual factors such as age and gender but also
      other, unknown factors influence the expression of the PPR. For example, PPRs
      occur during adolescence and can disappear at a later age. As a consequence, it
      is difficult to assign nonaffected disease status correctly. Autosomal dominant
      inheritance has been found in clinical studies of relatives of PPR-positive
      epilepsy and nonepilepsy subjects. Genetic heterogeneity of the PPR is obvious
      because the PPR also can be evoked in a number of autosomal recessive diseases.
      PPR is most commonly associated with idiopathic generalized epilepsies (IGEs)
      such as juvenile myoclonic epilepsy (JME). This comorbidity suggests that a
      genetic factor involved in photosensitivity also may influence the susceptibility
      for JME. Finding the gene for PPR also might represent a step forward in
      unraveling the genetic background of JME. The search for the genetic factors
      causing PPRs should focus on the genes affected in such epilepsies, such as genes
      (coding) for ion channels and neurotransmitters and their receptors. The
      expression of defined proteins with as-yet-undetermined functions, is changed in
      a few types of epilepsies with a mendelian mode of inheritance. These additional
      genes and the human equivalents of the genes found to be mutated in animal models
      also are candidates for molecular genetic studies of the PPR.

PMID- 14706041
TI  - Epilepsy and videogames.
AB  - Since the first case of videogame (VG) epilepsy was reported in 1981, many cases
      of seizures triggered by VGs were reported, not only in photosensitive, but also
      in non-photosensitive children and adolescents with epilepsy. We provide an
      overview of the literature with overall conclusions and recommendations regarding
      VG playing. Specific preventive measures concerning the physical characteristics
      of images included in commercially available VGs (flash rate, choice of colors,
      patterns, and contrast) can lead in the future to a clear decrease of this
      problem. In addition to the positive effect of such measures, the collaborative
      studies performed in France and in the rest of Europe have stressed the
      importance of a safe distance to the screen of > or = 2 m, and the less
      provocative role of 100-Hz screens.

PMID- 14706042
TI  - Visual reflex seizures induced by complex stimuli.
AB  - Visual reflex seizures induced by complex stimuli may be triggered by patterned
      and flashing displays that are now ubiquitous. The seizures may be clinically
      generalized, but unilateral and bilateral myoclonic attacks also may be
      triggered, especially in patients with juvenile myoclonic epilepsy, and recently,
      clearly focal reflex occipital lobe seizures have been described. Some seizure
      triggering properties of video displays can be identified, such as perceived
      brightness, pattern, flicker frequency, and color. Knowledge of these is useful
      in planning individual treatment and in designing regulations for screen content
      of television broadcasts or for other video displays. Some subjects will also be
      sensitive to cognitive or action-programming activation, especially when playing
      video games, and this can increase the chance of seizure triggering. Nonspecific
      factors such as sleep deprivation, prolonged exposure, and drug or alcohol use
      also may play a role in reflex seizure occurrence.

PMID- 14706043
TI  - Photosensitivity: the magnitude of the problem.
AB  - Very few studies of photosensitivity or visual sensitive epilepsy could be called
      epidemiologic in the strict sense, that is, giving well-based incidence and
      prevalence rates of a well-defined clinical and electroencephalographic syndrome
      or group of syndromes. The available data suggest that photosensitivity is rare
      in the population as a whole, with an annual incidence rate around one case per
      100,000 population. The incidence goes up to almost six per 100,000 in the late
      adolescent period, the age group at the highest risk. Well-established concepts,
      such as statements that one in 4,000 of the general population or that 10% of all
      epilepsy patients would be photosensitive, should be reevaluated. The more likely
      figures are a lifetime prevalence of one in 10,000 in the general population,
      perhaps as low as 2%, of the epilepsy population. Further epidemiologic studies,
      sensu strictu, are warranted to settle the basic question of the real incidence
      and prevalence of photoparoxysmal responses (PPRs) and epilepsy with seizures
      provoked by visual stimuli in the community.

PMID- 14706044
TI  - EEG diagnostic procedures and special investigations in the assessment of
      photosensitivity.
AB  - Photosensitivity can be assessed in laboratory conditions with different methods.
      The most common procedure is intermittent photic stimulation (IPS), whose
      effectiveness in detecting photosensitivity depends largely on methodologic
      aspects. Although IPS is a widespread and routinely used procedure in EEG
      laboratories, only recently has a standardization of the IPS method been
      proposed. Furthermore, other modalities of visual stimulation, including pattern
      stimulation and low-luminance visual stimulation (LLVS), have proven their
      usefulness in detecting photosensitivity. We provide an overview of the
      methodologic aspects and clinical implications of these procedures, resulting
      from recent consensus meetings, and the diagnostic usefulness of the LLVS
      technique in photosensitive individuals whose seizures are triggered particularly
      by television images. Finally, we briefly illustrate the potential of advanced
      neurophysiological (magnetoencephalography and high-density EEG) and functional
      imaging techniques in the investigation of the pathophysiologic mechanisms
      underlying photosensitivity.

PMID- 14706045
TI  - Treatment of photosensitivity.
AB  - Not all visually sensitive patients need antiepileptic drug treatment, and even
      those who do can benefit from additional preventive measures. Visually provoked
      seizures, in particular, can be prevented or treated by avoiding or altering the
      triggering stimulus. Apart from individual preventive measures (use of specific
      television or video screens, colored glasses, etc.), prevention and warning on a
      larger scale are helpful. The choice for drug treatment will depend on the type
      of stimulus, the environment in which the person has to live and work, the
      frequency and severity of seizures, and the type of epileptic syndrome. A review
      is given of all treatment options with focus on the specific nonpharmacologic and
      pharmacologic tools used in clinical practice.

PMID- 14706046
TI  - Regulations: what next?
AB  - Television (TV) is the most provocative visual stimulus and evokes (first)
      seizures in susceptible children and adolescents, especially when flickering and
      patterned images are shown. This has led to the initiative to develop guidelines
      for broadcasters. The development of new types of TV screens will not remove the
      need for control of broadcast material. It could be argued that rather than
      protect the whole viewing audience by application of broadcasting guidelines,
      only those who are photosensitive should be protected. But maybe we should do
      both, because most known sensitive patients will benefit from greater safety and
      will not be dependent on fashionable ideas by commercial broadcasters that are
      not (yet) familiar with the guidelines. No such guidelines exist for video
      material, electronic screen games, and the Internet. It would be wise to adopt
      the guidelines for video material and electronic screen games.

PMID- 14706047
TI  - Inhibition of the renin-angiotensin system: added value in reducing
      cardiovascular and renal risk?

PMID- 14706048
TI  - Diabetic renal disease: from recent studies to improved clinical practice.

PMID- 14706049
TI  - Angiotensin receptor blockers as anti-hypertensive treatment for patients with
      diabetes mellitus: meta-analysis of controlled double-blind randomized trials.
AB  - AIMS: To assess the evidence for possible reduction of all-cause mortality,
      cardiovascular morbidity and mortality, and end-stage renal disease in diabetic
      patients treated with angiotensin II type 1 receptor blockers (ARBs) as an anti
      hypertensive treatment. METHODS: Systematic review and meta-analysis of
      randomized, double-blind controlled trials of at least 1 year's duration. ARBs
      were used in the intervention group vs. placebo or standard anti-hypertensive
      treatment in the control group. The main outcome measures were all-cause
      mortality, cardiovascular morbidity and mortality, and end-stage renal disease.
      RESULTS: Three studies fulfilled the inclusion criteria. Separate analyses were
      conducted for comparisons of ARBs with groups given placebo and those given
      standard anti-hypertensive treatment. There was no significant difference in
      mortality between the ARBs and placebo groups, with an estimated odds ratio (OR)
      of 0.99 [95% confidence interval (CI) 0.81, 1.20]. There was a non-significant
      difference in patients treated with ARBs compared with standard anti-hypertensive
      treatment, with an OR of 0.78 (95% CI 0.45, 1.36). No statistically significant
      difference in cardiovascular morbidity and mortality between the intervention and
      placebo groups was found, with an OR of 0.91 (95% CI 0.77, 1.08). When ARBs were
      compared with standard treatment, the OR was estimated at 0.85 (0.54, 1.33). Data
      on end-stage renal disease were available for two studies comparing ARBs vs.
      placebo and showed a statistically significant advantage of ARBs, with an OR of
      0.73 (95% CI 0.6, 0.89). As only one study compared end-stage renal disease
      outcome for ARBs vs. standard treatment, a meta-analysis was not possible. This
      study reported a considerable benefit of ARBs [OR = 0.73 (0.54, 1.01)] compared
      with the calcium channel blocker amlodipine. CONCLUSIONS: ARBs failed to show
      significant reduction in total mortality and cardiovascular morbidity and
      mortality in diabetic patients. The only statistical benefit was the reduction of
      end-stage renal disease compared with placebo. Therefore, at this time ARBs have
      not proved to be superior to standard anti-hypertensive treatment in diabetic
      patients.

PMID- 14706050
TI  - The long-term renal and retinal outcome of childhood-onset Type 1 diabetes.
AB  - AIMS: To quantify the influence of childhood onset on long-term renal and retinal
      outcome in Type 1 diabetes. METHODS: We used a population-based diabetes register
      to identify all Type 1 patients diagnosed before age 15 from 1960 to 1982 and
      resident in a defined catchment area in 1999. Those diagnosed before age 5, aged
      5-9 and 10-14 years were compared with a reference group diagnosed at age 21-25
      years over the same period. RESULTS: Compared with adult-onset controls,
      proteinuria occurred earlier (P = 0.02) and nephropathy outcome was worse (P =
      0.008) in childhood-onset diabetes. The risk of developing microalbuminuria was
      greater in childhood-onset diabetes: odds ratio 2.6 (95% confidence interval 1.4
      4.9, P = 0.003). The relative risk of established nephropathy was 3.8 (1.5-9.4, P
      = 0.005) with childhood onset. The number developing background retinopathy did
      not differ with age at onset but younger onset patients were more likely to need
      laser treatment: relative risk 2.1 (1.1-3.8, P = 0.02). This maintained visual
      outcome which was not significantly different between the various age at onset
      groups. CONCLUSIONS: Patients with onset of Type 1 diabetes before age 15 have
      substantially worse renal outcome and require more laser treatment than adult
      onset patients. Differences between those with onset before age 5, onset at 5-9
      and 10-14 years are small compared with the difference between childhood onset
      and adult onset. Events in the teenage years therefore appear to have a major
      adverse effect on the risk of developing long-term microvascular complications.

PMID- 14706051
TI  - Specialist general practitioners and diabetes clinics in primary care: a
      qualitative and descriptive evaluation.
AB  - AIMS: The aim of this study was to evaluate an innovative approach to the
      provision of primary care-based diabetes services in Bradford, UK. The service
      model differs from others in comprising 19 clinics which offer a specialist
      service, intermediate between primary and secondary care, to all patients within
      the Bradford area. METHODS: The study included: analysis of referral, attendance
      and register data; questionnaires to general practitioners (GPs) and specialist
      clinic providers; qualitative interviews with clinic and other professional staff
      and patients; and an economic analysis. RESULTS: The 19 clinics adopt a range of
      organizational models. In the first 3 1/2 years, 2415 patients were referred.
      There was a significant reduction in out-patient attendances at hospital, but
      also a significant increase in overall patient attendances. Specialist clinic
      patients differed from hospital patients in being older and having had diabetes
      for longer since diagnosis. Ten of the 14 clinics run by practising GPs attracted
      more referrals from within their practices than from outside. GPs and patients
      across the city believed the clinics were valuable, the main benefits being
      geographical accessibility, availability of specialists in a community setting,
      short waiting times for first appointments at most clinics, and continuity of
      staff. Their reservations included a lack of strategic planning in the location
      of clinics, long waiting times at some clinics, and poor communication at some
      clinics with referring GPs. The cost of the primary care clinics is similar to
      hospital clinics. CONCLUSIONS: This model of specialist primary care services
      offers an opportunity to develop diabetes services that are convenient to
      patients, popular with practitioners, and increase capacity. However, the
      shortcomings as well as the advantages of the model need to be addressed if it is
      to be implemented elsewhere or for other patient groups.

PMID- 14706052
TI  - Association between fasting glucose and C-reactive protein in middle-aged
      subjects.
AB  - AIMS: C-reactive protein (CRP), a marker of subclinical inflammation, predicts
      the occurrence of coronary heart disease in healthy subjects. Hyperglycaemia is
      known to stimulate the release of inflammatory cytokines from various cell types
      and can lead to the induction and secretion of acute-phase reactants by
      adipocytes. The aim of the present study was to determine the relation between
      glycaemic status and CRP in healthy subjects. METHODS: We studied the relation of
      high-sensitivity CRP to fasting glucose and other components of the metabolic
      syndrome in a population-based cross-sectional study (n = 1000; age 50 +/- 9
      years). RESULTS: Plasma CRP levels increased continuously from the lowest
      quartile of normal fasting glucose level to impaired fasting glucose and to
      diabetes (ln CRP 0.47 +/- 0.09, 0.95 +/- 0.12, and 1.11 +/- 0.13, respectively;
      Ptrend < 0.0001). Increasing CRP with higher fasting glucose levels was apparent
      even among subjects with fasting glucose in the normal range (Ptrend = 0.039),
      and subjects with fasting glucose level in the upper quartile of normal fasting
      glucose had higher CRP levels compared with subjects in the lower quartile (P =
      0.035). There was a positive crude correlation between CRP and smoking, post
      menopausal hormone use, body mass index, fasting glucose, triglycerides,
      hypertension, and uric acid (r = 0.11-0.36, P = 0.002-0.0001). A negative
      correlation was found between CRP and HDL-cholesterol (r = 0.12, P < 0.0001) and
      physical activity (r = 0.11, P = 0.002). After adjustment for potential
      confounders in a stepwise multivariate linear regression model, fasting glucose
      remained significantly and independently related to CRP levels (correlation
      coefficient 0.06; 95% confidence interval 0.014-0.11, P = 0.011). CONCLUSIONS:
      Fasting glucose is significantly and positively associated with plasma CRP in
      middle-aged subjects. CRP levels increase continuously across the spectrum of
      fasting glucose, beginning in the lowest quartile of normal fasting glucose. This
      finding suggests that a proinflammatory effect may contribute to the adverse
      cardiovascular outcome associated with diabetes, impaired fasting glucose, and
      increasing glucose levels within the normal range.

PMID- 14706053
TI  - Diabetes-related inequalities in health status and financial barriers to health
      care access in a population-based study.
AB  - AIMS: We evaluated the relationship between diabetes, health status, household
      income and expenditure on health care in the general population in Trinidad.
      METHODS: Multistage sampling of 300 households was used to select a sample of 548
      adults aged > or = 25 years. There were 64 (12%) who reported a diagnosis of
      diabetes. Comparison was made with 128 non-diabetic controls who were frequency
      matched for age and sex. RESULTS: Subjects with diabetes had lower income levels
      than non-diabetic controls [income < or = US dollars 533 per month for 66%
      diabetes cases and 48% controls, test for trend P = 0.007]. Compared with
      controls, subjects with diabetes were less likely to have good or very good self
      rated health (diabetes 32%, controls 67%; P < 0.001), and more frequently
      reported long-standing illness, limitation of activities, visual impairment, or
      self-reported history of high blood pressure, angina or heart attack. Subjects
      with diabetes (11%) were less likely than controls (30%) to have private health
      insurance (P = 0.005). Diabetic subjects (35%) were more likely than controls
      (16%) to have incurred expenditure on doctors' services in the last 4 weeks (P =
      0.021). CONCLUSIONS: Diabetes is associated with worse health status and more
      frequent expenditure on medical services but greater financial barriers to access
      in terms of low income and lack of health insurance. Policies for diabetes should
      specifically address the problem of income-related variations in risk of
      diabetes, health care needs and barriers to uptake of preventive and treatment
      services, otherwise inequalities in health from this condition may increase.

PMID- 14706054
TI  - The Metabolic Syndrome is an independent predictor of cardiovascular disease in
      Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications
      Study.
AB  - AIMS: To evaluate the cardiovascular risk associated with the presence of the
      Metabolic Syndrome in Type 2 diabetic subjects. METHODS: Subjects with the
      Metabolic Syndrome, defined by WHO criteria, were identified in a large sample of
      non-insulin-treated Type 2 diabetic patients examined within the Verona Diabetes
      Complications Study (n = 946). At baseline and after a mean of 4.5 years follow
      up, cardiovascular disease (CVD) was assessed by medical history, physical
      examination, electrocardiogram (ECG) and echo-duplex of carotid and lower limb
      arteries. Death certificates and medical records of subjects who died during the
      follow-up were scrutinized in order to identify CVD deaths. In statistical
      analyses, CVD was considered as an aggregate end-point, including fatal and non
      fatal coronary, cerebrovascular and peripheral vascular disease as well as
      ischaemic ECG abnormalities and vascular lesions at the echo-duplex. RESULTS: The
      proportion of subjects with the Metabolic Syndrome was very high (92.3%). At the
      baseline, 31.7% of subjects were coded positive for CVD, which was more prevalent
      in subjects with the Metabolic Syndrome (32.9 vs. 17.8%, P = 0.005). Among
      subjects free of CVD at the baseline (n = 559), CVD events during the follow-up
      were significantly increased in patients with the Metabolic Syndrome as compared
      with those without it (19.9% vs. 3.9%, P < 0.001). Multiple logistic regression
      analysis showed that, along with sex, age, smoking and HbA1c, the presence of the
      Metabolic Syndrome independently predicted prevalent (OR 2.01, P = 0.045) and
      incident CVD (OR 4.89, P = 0.031). CONCLUSIONS: In Type 2 diabetes, the presence
      of the Metabolic Syndrome is associated with an almost 5-fold increase in CVD
      risk.

PMID- 14706055
TI  - Insulin sensitivity in physically fit and unfit children of parents with Type 2
      diabetes.
AB  - AIMS: First-degree relatives of patients with Type 2 diabetes mellitus (T2DM) are
      often reported to be insulin resistant. We wanted to identify early metabolic
      abnormalities in this condition, and determine whether they are altered by
      regular physical training. METHODS: We measured insulin sensitivity using the
      euglycaemic glucose clamp technique and insulin response to oral glucose in 10
      unfit (did not participate in routine physical exercise) offspring of T2DM
      parents and 10 unfit control subjects, and compared them with six fit (routinely
      swam for 3 h/day 5 days/week) offspring of T2DM parents and six fit controls with
      no family history of T2DM. RESULTS: Unfit offspring had a higher plasma glucose
      response than the other three groups. The mean area under the glucose curve was
      also significantly higher in unfit offspring than in the other three groups (12.6
      +/- 0.6 vs. 10.4 +/- 0.4, 9.6 +/- 0.5, and 9.5 +/- 0.7 mmol/l per hour for the
      unfit controls, fit offspring and fit controls, respectively; P < 0.05). The
      corresponding insulin response of unfit offspring was significantly higher at 60
      min in the oral glucose tolerance test (OGTT) that that of fit offspring or fit
      controls. In addition, the mean area under the insulin curve was significantly
      greater in unfit offspring than in either fit offspring or fit controls (868 +/-
      172 vs. 294 +/- 71, 287 +/- 43 mmol/l per hour, respectively; P < 0.05).
      Moreover, the glucose disposal rate (GDR), measured using a euglycaemic clamp,
      was significantly lower in unfit and fit offspring than in unfit and fit controls
      (5.6 +/- 0.3 vs. 8.6 +/- 0.3 mg/kg per minute; P < 0.01 and 9.3 +/- 0.9 vs. 12.1
      +/- 0.8 mg/kg per minute, respectively; P < 0.015), whereas the GDR was similar
      in unfit controls and fit offspring (8.6 +/- 0.4 vs. 9.3 +/- 0.9 mg/kg per
      minute; P > 0.05). CONCLUSION: These results support the concept that early
      metabolic abnormalities, as reflected by a decreased GDR (insulin sensitivity) in
      the offspring of T2DM patients, may be improved by increased physical fitness.

PMID- 14706056
TI  - The concentrations of short-chain fatty acids and other microflora-associated
      characteristics in faeces from children with newly diagnosed Type 1 diabetes and
      control children and their family members.
AB  - AIMS: The gut flora is quantitatively the most important source of microbial
      stimulation and may provide a primary signal in the maturation of the immune
      system. We compared the microflora-associated characteristics (MACs) in 22
      children with newly diagnosed diabetes, 27 healthy controls, and their family
      members to see if there were differences between the children and if there was a
      familial pattern. METHODS: The MACs were assessed by determining the
      concentrations of eight short-chain fatty acids (SCFA), mucin, urobilin, b
      aspartylglycine, coprastanol and faecal tryptic activity (FTA). RESULTS: There
      were no statistically significant differences between the concentrations of SCFA
      in the diabetes and control children. Members of families with a diabetic child
      had a higher concentration of acetic acid (P < 0.02) and lower concentrations of
      several other SCFAs than control families (P < 0.05-0.02). The other MACs showed
      no differences between the children or between the two family groups. CONCLUSION:
      In this pilot study we saw no differences in the MACs between children with
      diabetes and their controls. There were, however, some differences between the
      family members of diabetic children and controls that may indicate a familial
      pattern regarding the production of SCFAs by the gut flora. The role of the gut
      flora in relation to the risk of developing Type 1 diabetes needs to be analysed
      in larger and/or prospective studies.

PMID- 14706057
TI  - Gestational diabetes affects platelet behaviour through modified oxidative
      radical metabolism.
AB  - AIMS: Patients with Type 1 and Type 2 diabetes mellitus show altered platelet
      function including decreased nitric oxide synthase (NOS) activity and increased
      peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical
      condition which is ideal for evaluating short-term effects of impaired glucose
      metabolism, ruling out the possibility that the platelet abnormalities are a
      consequence of diabetic complications. The aim of the present work was to study
      NO metabolism in platelets from pregnant women with GDM. The production of
      peroxides was also studied as it is strongly involved in peroxynitrite formation.
      METHODS: Platelet NOS activity and peroxynitrite production, levels of
      hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet
      membranes in the basal state and after in vitro peroxidative stress with
      phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy
      pregnant women (pregnant controls) of comparable age and gestational age, and 15
      healthy non-pregnant women (controls). RESULTS: NOS activity was significantly
      increased in both groups of pregnant women compared with non-pregnant ones, and
      in GDM women compared with pregnant controls. Production of peroxynitrite was
      higher in GDM women than in pregnant controls, who also had significantly reduced
      production compared with non-pregnant women. Basal levels of peroxidation of the
      platelet membranes evaluated either by hydroperoxide content and TBARS levels or
      the susceptibility to peroxidation were increased in GDM patients in comparison
      with both control groups. CONCLUSIONS: We have shown a modification in platelet
      NO and peroxynitrite production and an increase in platelet indicators of
      oxidative stress in GDM women compared with healthy pregnant women which might be
      at the basis of a cellular dysfunction.

PMID- 14706058
TI  - Nine weeks of bedtime diazoxide is well tolerated and improves beta-cell function
      in subjects with Type 2 diabetes.
AB  - AIMS: To test whether a bedtime dose of diazoxide can improve daytime beta-cell
      function without side-effects in Type 2 diabetes. METHODS: A double-blind
      randomized study was performed in 27 Type 2 diabetic subjects (17 male, 10
      female) who were treated with bedtime insulin and metformin. Subjects received
      either bedtime diazoxide, 100 mg, or placebo for 9 weeks. Duplicate C-peptide
      glucagon tests were performed before and in the last days of intervention.
      RESULTS: No side-effects of diazoxide were detected. Treatment with diazoxide did
      not incur any increase in bedtime insulin. C-peptide responses to glucagon tended
      to increase: 0.15 +/- 0.06 nmol/l vs. -0.01 +/- 0.04 nmol/l for placebo, P < 0.06
      for difference. Corresponding effects on insulin were 66.2 +/- 41.7 pmol/l for
      diazoxide vs. -84.2 +/- 51.5 for placebo, P < 0.03. Treatment with diazoxide
      decreased fasting glucagon levels by 41% vs. placebo, P < 0.03. Glycated
      haemoglobin (HbA1c) levels were not affected, whereas levels of blood glucose
      post breakfast were higher during diazoxide (1.34 +/- 0.43 mmol/l, P < 0.01 vs.
      placebo). CONCLUSIONS: Bedtime treatment with diazoxide in Type 2 diabetic
      subjects on bedtime insulin and metformin has no significant side-effects, does
      not increase bedtime insulin supplementation, tends to ameliorate beta-cell
      function but fails to improve metabolic control.

PMID- 14706059
TI  - Type 2 diabetes in Tirana City, Albania: a rapid increase in a country in
      transition.
AB  - AIMS: To determine how the prevalence of Type 2 diabetes mellitus has changed in
      Tirana, the capital of Albania, over 20 years. METHODS: Cluster sampling was used
      to select 700 households including 1540 adults 25 years of age and over in Tirana
      City, Albania in 2001. RESULTS: Of 1540 potential subjects, 1120 participated
      (response rate 72.7%). Using the 1985 WHO criteria to provide comparability with
      earlier data, the overall prevalence of Type 2 diabetes mellitus in the age group
      25+ was 6.3% (95% confidence interval 4.8-7.7); 6.9% (4.8-9.1%) male; 5.6% (3.8
      7.5%) female. The age-adjusted prevalence in those aged 25+ was 5.4%. Of
      respondents, 3.4% were known to have diabetes, and 2.9% were newly identified
      through the survey. The prevalence of diabetes increased with age, although among
      men there was a slight decline after age 65. Impaired glucose tolerance was found
      in a further 2.9% of respondents, again increasing with age. The prevalence of
      diabetes has increased significantly since 1980, doubling in the age group 50+.
      Use of the 1999 WHO diagnostic criteria produces a higher unadjusted prevalence,
      at 9.7% (8-11.4%). In a logistic regression model, obesity and family history
      were independent determinants of the probability of having diabetes. Among those
      known to have diabetes, control was poor. CONCLUSIONS: The prevalence of diabetes
      in Albania has increased rapidly, consistent with what has been seen in other
      countries undergoing rapid modernization. It is likely to increase further in the
      future, with important implications for health policy.

PMID- 14706060
TI  - Automated detection of diabetic retinopathy in digital retinal images: a tool for
      diabetic retinopathy screening.
AB  - AIMS: To develop a system to detect automatically features of diabetic
      retinopathy in colour digital retinal images and to evaluate its potential in
      diabetic retinopathy screening. METHODS: Macular centred 45 degrees colour
      retinal images from 1273 patients in an inner city diabetic retinopathy screening
      programme. A system was used involving pre-processing to standardize colour and
      enhance contrast, segmentation to reveal possible lesions and classification of
      lesions using an artificial neural network. The system was trained using a subset
      of images from 500 patients and evaluated by comparing its performance with a
      human grader on a test set of images from 773 patients. RESULTS: Maximum
      sensitivity for detection of any retinopathy on a per patient basis was 95.1%,
      accompanied by specificity of 46.3%. Specificity could be increased as far as
      78.9% but was accompanied by a fall in sensitivity to 70.8%. At a setting with
      94.8% sensitivity and 52.8% specificity, no cases of sight-threatening
      retinopathy were missed (retinopathy warranting immediate ophthalmology referral
      or re-examination sooner than 1 year by National Institute for Clinical
      Excellence criteria). If the system was implemented at 94.8% sensitivity setting
      over half the images with no retinopathy would be correctly identified, reducing
      the need for a human grader to examine images in 1/3 of patients. CONCLUSION:
      This system could be used when screening for diabetic retinopathy. At 94.8%
      sensitivity setting the number of normal images requiring examination by a human
      grader could be halved.

PMID- 14706061
TI  - Regional differences in risk factors and clinical presentation of diabetic foot
      lesions.
AB  - BACKGROUND: Problems associated with the diabetic foot are worldwide. However,
      there may be regional variation among risk factors and clinical presentation.
      Prospective comparative data concerning this topic are rare. AIM: To determine
      differences in underlying risk factors and clinical presentation of foot problems
      among people with diabetes in different regions. PATIENTS AND METHODS: Six
      hundred and thirteen consecutive patients with diabetic foot lesions from three
      centres [Soest-Germany (GER), Dar-es-Salaam, Tanzania (TAN) and Chennai, India
      (IND)] were included during the period June 1998 through December 1999. Diabetes
      related data, risk-factor profiles, and lesion-related data were collected for
      each patient. Due to varying proportions of recurrent lesions among the centres,
      only data from patients with newly presenting diabetic foot lesion were analysed.
      RESULTS: Of the 613 patients sampled, 368 (60%) were treated for newly presenting
      diabetic foot lesion. In all three centres, patients were predominately male and
      had Type 2 diabetes. The average diabetes duration until the onset of the initial
      foot lesion was 14 years in GER and 12 years in IND, but only 5 years in TAN. The
      corresponding patient ages were 71, 56 and 51 years. Neuropathy was common to
      patients in all three centres. Peripheral vascular disease (PVD) was a frequent
      risk factor in GER (48%). In TAN and IND it was far less common (12 and 13%),
      probably due to younger patient populations, shorter diabetes duration and lower
      proportions of smokers. Inadequate footwear was the most common cause of foot
      lesions in GER (19%), while lack of footwear, irregular foot care and burns were
      the primary precipitating factors among patients in TAN and IND. CONCLUSION:
      Similarities in different regions of the world among people with diabetes
      suffering newly presenting foot lesions include a predominance of males and
      patients with Type 2 diabetes, as well as a high frequency of diabetic
      neuropathy. However, differences concerning age, diabetes duration, peripheral
      vascular disease, and precipitating factors contributing to injury are also
      observed.

PMID- 14706062
TI  - Sudden hearing loss as a first complication of long-standing Type 1 diabetes
      mellitus: a case report.
AB  - The term 'sudden hypoacusis' describes a hearing loss of a rapid onset and
      unknown origin that can progress to severe deafness. Its pathophysiology is still
      unknown, the proposed aetiological mechanisms being vascular disease or
      autoimmune reaction. We present the case of a 19-year-old woman with Type 1
      diabetes mellitus who experienced sudden hearing loss on her right side. She had
      no complications related to diabetes. After being referred to the hospital she
      was diagnosed with sudden sensorineural right-sided hearing loss accompanied by
      high frequency tinnitus. After administration of vasoactive drugs, there was
      partial improvement after 7 days, followed by gradual improvement over the next 4
      weeks to 5 months. The tinnitus did not disappear completely. We conclude that
      hearing organ disturbances can be present in Type 1 diabetes and represent an
      early complication.

PMID- 14706065
TI  - Sex determination in fish: Lessons from the sex-determining gene of the teleost
      medaka, Oryzias latipes.
AB  - Although sex determination systems in animals are diverse, sex-determining genes
      have been identified only in mammals and some invertebrates. Recently, DMY (DM
      domain gene on the Y chromosome) has been found in the sex-determining region on
      the Y chromosome of the teleost medaka fish, Oryzias latipes. Functional and
      expression analyses of DMY show it to be the leading candidate for the male
      determining master gene of the medaka. Although some work is required to define
      DMY as the master sex-determining gene, medaka is expected to be a good
      experimental animal for investigating the precise mechanisms involved in primary
      sex determination in non-mammalian vertebrates. In this article, the process of
      identification of DMY and is summarized and the origins of DMY and sexual
      development of the medaka's gonads are reviewed. In addition, putative functions
      of DMY are discussed.

PMID- 14706066
TI  - Protein tyrosine phosphatases in Chaetopterus egg activation.
AB  - Changes in protein tyrosine phosphorylation are an essential aspect of egg
      activation after fertilization. Such changes result from the net contributions of
      both tyrosine kinases and phosphatases (PTP). This study was conducted to
      determine what role(s) PTP may have in egg activation. We identified four novel
      PTP in Chaetopterus pergamentaceus oocytes, cpPTPNT6, cpPTPNT7, cpPTPR2B, and
      cpPTPR2A, that have significant homology to, respectively, human PTPsigma, -rho, 
      D2 and -BAS. The first two are cytosolic and the latter two are transmembrane.
      Several PTP inhibitors were tested to see if they would affect Chaetopterus
      pergamentaceus fertilization. Eggs treated with beta-bromo-4-hydroxyacetophenone
      (PTP inhibitor 1) exhibited microvillar elongation, which is a sign of cortical
      changes resulting from activation. Those treated with Na3VO4 underwent full
      parthenogenetic activation, including polar body formation and pseudocleavage and
      did so independently of extracellular Ca2+, which is required for the Ca2+
      oscillations that initiate development after fertilization. Fluorescence
      microscopy identified phosphotyrosine-containing proteins in the cortex and
      around the nucleus of vanadate-activated eggs, whereas in fertilized eggs they
      were concentrated only in the cortex. Immunoblots of vanadate-activated and
      fertilized eggs showed tyrosine hyperphosphorylation of approximately 140 kDa
      protein. These results suggest that PTP most likely maintain the egg in an
      inactive state by dephosphorylation of proteins independent of the Ca2+
      oscillations in the activation process.

PMID- 14706067
TI  - A trial for induction of supernumerary primordial germ cells in Xenopus tadpoles
      by injecting RNA of Xenopus vasa homologue into germline cells of 32-cell
      embryos.
AB  - Whether overexpression of Xenopus vasa homologue or Xenopus vasa-like gene 1
      (XVLG1) in germline cells of Xenopus embryos can induce supernumerary primordial
      germ cells (PGC) at tadpole stage was investigated. XVLG1 RNA (0.1-2.0 ng) and
      beta-gal RNA (0.5 ng) were injected into one of, usually, four germ plasm-bearing
      cells (GPBC) of 32-cell embryos, with the beta-gal RNA (2.0 ng) serving as both
      lineage tracer and control for XVLG1 RNA. The total number of PGC, including X
      gal-stained and unstained PGC of injected and uninjected GPBC origins
      respectively, was examined in the experimental tadpoles developed from the
      injected embryos. The injected RNA, XVLG1 and beta-gal RNA, were translated,
      resulting in a large amount of corresponding proteins in presumptive PGC (pPGC)
      as well as in somatic cells derived from the injected GPBC. Nevertheless, the
      average number of total PGC per tadpole found in the experimental tadpoles from
      the XVLG1 RNA-injected embryos was not significantly different from that of beta
      gal RNA-injected ones, irrespective of the injected dose of XVLG1 RNA. This
      indicates that the extra XVLG1 protein in pPGC is not sufficient to increase the
      number of PGC in the tadpoles.

PMID- 14706068
TI  - Further studies on thermal treatment of two-cell stage embryos to produce
      complete embryonic stem-cell-derived mice by cell-aggregation methods.
AB  - Employing aggregation techniques with two embryonic sources, one from two-cell
      stage embryos treated by thermal stimulation and the other from mouse embryonic
      stem (ES) cells that had been obtained from a feeder layer, simple and most
      effective methods of producing a complete generation of mice from ES cells were
      explored. Although thermal treatment affected embryos at various developmental
      stages, the embryos at the two-cell stage of development were selected because of
      the remarkably reduced number of cells present in the inner cell mass (ICM) at
      blastocyst stage after thermal conditioning. Under these conditions, a
      combination of thermally treated host embryos and an aggregated ES cell-clump was
      found to produce a high rate of live newborns by natural delivery. That the
      newborns were completely derived from ES cells was checked by two criteria:
      microsatellite analysis and coat color analysis. Importantly, all of these mice
      were healthy and fertile. The aggregation techniques reported here might well be
      applied to other animal species whose ES cells form stable colonies on a feeder
      layer.

PMID- 14706069
TI  - Differentiation of chondrocytes and scleroblasts during dorsal fin skeletogenesis
      in flounder larvae.
AB  - In teleosts, the embryonic fin fold consists of a peridermis, an underlying
      epidermis and a small number of mesenchymal cells. Beginning from such a simple
      structure, the fin skeletons, including the proximal and distal radials and
      lepidotrichia (finrays), develop in the dorsal fin fold at the larval stage.
      Their process of skeletogenesis and embryonic origin are unclear. Using flounder
      larvae, we report the differentiation process for chondrocytes and scleroblasts
      prior to fin skeletogenesis and the effects of retinoic acid (RA) on it. In early
      larvae, the mesenchymal cells grow between the epidermis and spinal cord to form
      a line of periodical condensations, which are proximal radial primordia, to
      produce chondrocytes. The prescleroblasts, which ossify the proximal radial
      cartilages, differentiate in the mesenchymal cells remaining between the
      cartilages. Then, mesenchymal condensations occur between the distal ends of the
      proximal radials, forming distal radial primordia, to produce chondrocytes.
      Simultaneously, condensations occur between the distal radial primordia and
      peridermis, which are lepidotrichia primordia, to produce prescleroblasts.
      Exogenous RA specifically inhibits the mesenchymal condensation prior to the
      proximal radial formation together with the down-regulation of sonic hedgehog
      (shh) and patched (pta) expression, resulting in the loss of proximal radials.
      Thus, it was indicated that differentiation of the precursor cells of radials and
      lepidotrichia begins in the proximal part of the fin fold and that the initial
      mesenchymal condensation prior to the proximal radial formation is highly
      susceptible to the effects of RA. Lepidotrichia formation does not occur where
      proximal radials are absent, indicating that lepidotrichia differentiation
      requires interaction with the radial cartilages. To examine the suggestion that
      neural crest cells contribute to the medial fin skeletons, we localized the HNK-1
      positive cells in flounder embryos and slug and msxb-positive cells in
      pufferfish, Fugu rubripes, embryos. That the positive cells commonly arrive at
      the proximal part of the fin fold does not contradict the suggestion, but their
      final destiny as radial chondrocytes or lepidotrichia scleroblasts, should be
      further investigated.

PMID- 14706070
TI  - Defective smooth muscle development in qkI-deficient mice.
AB  - The qkI gene encodes an RNA binding protein which was identified as a candidate
      for the classical neurologic mutation, qkv. Although qkI is involved in glial
      cell differentiation in mice, qkI homologues in other species play important
      roles in various developmental processes. Here, we show a novel function of qkI
      in smooth muscle cell differentiation during embryonic blood vessel formation.
      qkI null embryos died between embryonic day 9.5 and 10.5. Embryonic day 9.5 qkI
      null embryos showed a lack of large vitelline vessels in the yolk sacs, kinky
      neural tubes, pericardial effusion, open neural tubes and incomplete embryonic
      turning. Using X-gal and immunohistochemical staining, qkI is first shown to be
      expressed in endothelial cells and smooth muscle cells. Analyses of qkI null
      embryos in vivo and in vitro revealed that the vitelline artery was too thin to
      connect properly to the yolk sac, thereby preventing remodeling of the yolk sac
      vasculature, and that the vitelline vessel was deficient in smooth muscle cells.
      Addition of QKI and platelet-endothelial cell adhesion molecule-1 positive cells
      to an in vitro para-aortic splanchnopleural culture of qkI null embryos rescued
      the vascular remodeling deficit. These data suggest that QKI protein has a
      critical regulatory role in smooth muscle cell development, and that smooth
      muscle cells play an important role in inducing vascular remodeling.

PMID- 14706071
TI  - In vitro induction and transplantation of eye during early Xenopus development.
AB  - A vertebrate eye was induced via a series of coordinated inductive interactions.
      Here, we describe a novel in vitro system to induce eye formation at high
      frequency using Xenopus early gastrulae. The eye formed in vitro is
      morphologically similar to the normal eye. When the in vitro eye was transplanted
      into a stage-33 tadpole, the optic nerve was seen extending from the grafted eye
      to the tectum of the host brain and the in vitro eye graft was retained after
      metamorphosis. In addition, we transplanted the eye formed in vitro into a
      tadpole with both eyes removed. The resultant juvenile frogs could perceive
      brightness using the grafted eye and thereby control their skin color, suggesting
      that the eye formed in vitro could function normally.

PMID- 14706072
TI  - Behavior and differentiation process of pigment cells in a tropical sea urchin
      Echinometra mathaei.
AB  - The behavior and differentiation processes of pigment cells were studied in
      embryos of a tropical sea urchin Echinometra mathaei, whose egg volume was one
      half of those of well-known sea urchin species. Owing to earlier accumulation of
      pigments, pigment cells could be detected in the vegetal plate even before the
      onset of gastrulation, distributed dorsally in a hemi-circle near the center of
      the vegetal plate. Although some pigment cells left the archenteron during
      gastrulation, most of them remained at the archenteron tip. At the end of
      gastrulation, pigment cells left the archenteron and migrated into the
      blastocoele. Unlike pigment cells in typical sea urchins, however, they did not
      enter the ectoderm, and stayed in the blastocoele even at the pluteus stage. It
      is of interest that the majority of pigment cells were distributed in the
      vicinity of the larval skeleton. Aphidicolin treatment revealed that eight
      blastomeres were specific to pigment cell lineage after the eighth cleavage, one
      cell cycle earlier than that in well-known sea urchins. The pigment founder cells
      divided twice, and the number of pigment cells was around 32 at the pluteus
      stage. It was also found that the differentiation of pigment cells was blocked
      with Ni2+, whereas the treatment was effective only during the first division
      cycle of the founder cells.

PMID- 14706073
TI  - Hoxa-11 and Hoxa-13 are involved in repression of MyoD during limb muscle
      development.
AB  - Under the influence of the limb mesenchyme, Hoxa-11 is expressed in migrating and
      proliferating premyoblasts in the limb field and Hoxa-13 is induced in subdomains
      of congregated limb muscle masses. To evaluate the roles of Hoxa-11 and Hoxa-13
      in myogenesis of the limb, we performed electroporation in ovo to force
      expression of these Hox genes in limb muscle precursors. In the presence of
      ectopic Hoxa-11, expression of MyoD was blocked transiently. In C2C12 myoblasts,
      transfection of Hoxa-11 also repressed the expression of endogenous MyoD. Forced
      expression of Hoxa-13 resulted in more pronounced repression of MyoD in both limb
      and C2C12 myoblasts. In contrast, targeted disruption of Hoxa-13 gave rise to
      enhanced expression of MyoD in the flexor carpi radialis muscle, a forearm muscle
      that normally expressed Hoxa-13. These results suggest that Hoxa-11 and Hoxa-13
      are involved in the negative regulation of MyoD expression in limb muscle
      precursors.

PMID- 14706075
TI  - Identification and characterization of novel calcium-binding proteins of
      Dictyostelium and their spatial expression patterns during development.
AB  - Five putative Ca2(+)-binding proteins, CBP5, 6, 7, 8 and 9, all having EF-hand
      motifs, were found by searching the Dictyostelium cDNA database
      (http://www.csm.biol.tsukuba.ac.jp/cDNAproject.html). 45Ca2(+)-overlay
      experiments revealed that four of these (excluding CBP9) are real Ca2(+)-binding
      proteins. Northern blot analysis revealed that the genes encoding CBP5, 6, 7 and
      8 are all developmentally regulated. In situ hybridization analyses revealed that
      spatial expression of these genes was regulated in several different ways. CBP1,
      2, 3, 5, 6 and 7 are expressed in prespore cells in the slug stage. Transcripts
      of the genes for CBP1 and 5 are enriched in prestalk subtype PstO cells. In
      contrast, CBP4 is expressed predominantly in PstO cells. CBP8 is evenly expressed
      at a very low level throughout the whole slug. Such distinct spatial expression
      patterns suggest that the CBP might be involved in morphogenesis and might have
      their own roles either in prespore or in prestalk cell differentiation of
      Dictyostelium.

PMID- 14706074
TI  - Long-term culture of Xenopus presumptive ectoderm in a nutrient-supplemented
      culture medium.
AB  - Animal cap assay is a useful experimental model for investigating the activity of
      inducers in amphibian development. This assay has revealed that activin A is a
      potent mesoderm-inducing factor. However, it has been very difficult to induce
      highly differentiated tissues such as cartilage in a 3-4 day culture period. It
      was recently reported that jaw cartilage was induced in vitro in an animal cap
      that had been cultured for 14 days in Steinberg's solution using the sandwich
      culture method and activin A. Under these conditions, necrosis was occasionally
      observed in the explants. In this study, we have achieved long-term animal cap
      cultures in a nutrient-supplemented culture medium designated RDX. This medium
      was made by modifying the saline concentration of the RD medium previously
      developed as a basal medium for the serum-free culture of various kinds of
      mammalian cells. The explants cultured in RDX grew more vigorously compared with
      those in Steinberg's solution. RDX medium promoted a wider variety of tissue
      induction and gene expression in the animal caps than Steinberg's solution, and
      also increased the frequency of cartilage induction. Therefore, the supplemental
      nutrients may support and promote the differentiation of cartilage. This long
      term culture method using RDX medium is useful for studying the differentiation
      of tissues or organs such as cartilage in vitro.

PMID- 14706076
TI  - Molecular identification of the skin transformation center of anuran larval skin
      using genes of Rana adult keratin (RAK) and SPARC as probes.
AB  - Anuran larval skin undergoes a process of metamorphosis into pre-adult and adult
      skin. Basal skein, larval basal and adult basal cells are basement membrane
      attaching cells in the larval, pre-adult and adult epidermis, respectively, and
      are identified as cells expressing genes of RLK (Rana larval keratin), both RLK
      and RAK (Rana adult keratin), and RAK. Larval to pre-adult skin conversion takes
      place in the histological entity called the skin transformation center (STC). The
      present study performed a cDNA subtractive gene screening on cDNA of the larval
      and the pre-adult skin, and cloned the secreted protein acidic and rich in
      cysteine (SPARC) gene as an upregulated gene in the larva to pre-adult skin
      conversion. RAK gene-positive basal skein cells and fibroblasts in and around the
      STC were weakly and strongly sparc-positive, respectively. Using sparc and rak,
      we redefined the STC and visualized it on a histological section as an
      approximately 150 microm-long region that contained about 20 rak-negative and
      weakly sparc-positive basal cells. Intense sparc expression was observed in basal
      skein cells, but not in larval basal cells, suggesting that SPARC acts as a
      suppressor of rak during epidermal differentiation. This suggestion was tested by
      investigating the effect of SPARC on cultured larval basal cells. We observed
      that SPARC suppressed the expression of rak, but not rlk.

PMID- 14706077
TI  - Inhibition of mitogen activated protein kinase signaling affects gastrulation and
      spiculogenesis in the sea urchin embryo.
AB  - The mitogen activated protein (MAP) kinase signaling cascade has been implicated
      in a wide variety of events during early embryonic development. We investigated
      the profile of MAP kinase activity during early development in the sea urchin,
      Strongylocentrotus purpuratus, and tested if disruption of the MAP kinase
      signaling cascade has any effect on developmental events. MAP kinase undergoes a
      rapid, transient activation at the early blastula stage. After returning to basal
      levels, the activity again peaks at early gastrula stage and remains high through
      the pluteus stage. Immunostaining of early blastula stage embryos using
      antibodies revealed that a small subset of cells forming a ring at the vegetal
      plate exhibited active MAP kinase. In gastrula stage embryos, no specific subset
      of cells expressed enhanced levels of active enzyme. If the signaling cascade was
      inhibited at any time between the one cell and early blastula stage, gastrulation
      was delayed, and a significant percentage of embryos underwent exogastrulation.
      In embryos treated with MAP kinase signaling inhibitors after the blastula stage,
      gastrulation was normal but spiculogenesis was affected. The data suggest that
      MAP kinase signaling plays a role in gastrulation and spiculogenesis in sea
      urchin embryos.

PMID- 14706078
TI  - Analysis of gene expression in rabbit nuclear transfer embryos: Use of single
      embryo mRNA differential display.
AB  - Lack of or abnormal expression of developmentally important genes is believed to
      hamper early development of the nuclear transfer (NT) embryo. To identify stage
      specific genes in rabbit NT embryo development, mRNA differential display was
      used to compare the mRNA content of rabbit NT embryos at different developmental
      stages, from Metaphase II oocytes to 8-16-cell stage embryos. Thirty-four zygotic
      transcripts, which abruptly appeared at the 8-16-cell stage in rabbit NT embryos,
      were isolated; 11 of these were potential novel genes with no matches in the
      current databases. Of the remaining 23, 12 were matched with established sequence
      tags with functions uncharacterized and the other 11 were homologous to those in
      the European Molecular Biology Laboratory (EMBL) and GenBank databases. The
      differential expression of eight of the 34 amplicons were confirmed by reverse
      Northern blotting, and four positive clones were validated. Previous studies and
      present data indicated that these three genes were probably related to
      preimplantation rabbit embryo development.

PMID- 14706080
TI  - Invasive aspergillosis: current and future challenges in diagnosis and therapy.
AB  - Invasive aspergillosis is an increasingly common disease. While there have been
      significant advances in the past decade, significant challenges remain in terms
      of diagnosis and therapy. Some of the recent advances are outlined and future
      opportunities to improve the unacceptable mortality that is currently associated
      with this infection are considered.

PMID- 14706081
TI  - Molecular and diagnostic clinical virology in real time.
AB  - During the last decade, the application of both qualitative and quantitative
      nucleic acid detection techniques has had a major impact on diagnostics in
      clinical virology. Both signal and target amplification-based systems are
      currently used routinely in most if not all virology laboratories. However,
      commercial assays are only available for a very limited number of targets, and
      this has resulted in the development and introduction of assays developed in
      house for most viral targets. With improved and automated nucleic acid sample
      isolation techniques, as well as real-time detection methods, a new generation of
      assays for most clinically important viruses is being developed. These
      technological improvements also make it possible to generate results with a very
      short turnaround time. As an example of a more individual-patient disease
      management concept, we have introduced in our clinical setting the quantitative
      detection of Epstein-Barr virus (EBV) in T-cell-depleted allogeneic stem cell
      transplant patients. This has enabled us to develop models for pre-emptive anti-B
      cell immunotherapy for EBV reactivation, and for reducing not only the incidence
      of EBV lymphoproliferative disease (EBV-LPD), but the virus-related mortality. It
      is now also feasible to introduce molecular testing for those viruses that can
      easily be detected using classical virological methods, such as culture
      techniques or antigen detection. Prospective studies are needed to evaluate the
      clinical importance of the additional positive samples detected. It should,
      however, be clear that a complete exchange of technology is unlikely to occur,
      and that complementary methods should stay operational, making possible the
      discovery of new viruses. Furthermore, the ability to characterise viruses more
      easily by sequencing opens new possibilities for epidemiological studies. There
      is also an urgent need, with regard to molecular diagnostic methods, for the
      introduction and use of standardised materials and participation in international
      quality control programmes. Finally, with the introduction of a universal
      internal control throughout the whole procedure, the accuracy of the results
      generated is warranted.

PMID- 14706082
TI  - Efflux-mediated multiresistance in Gram-negative bacteria.
AB  - Multiresistance in Gram-negative pathogens, particularly Pseudomonas aeruginosa,
      Stenotrophomonas maltophilia, Acinetobacter spp. and the Enterobacteriaceae, is a
      significant problem in medicine today. While multiple mechanisms often contribute
      to multiresistance, a broadly distributed family of three-component multidrug
      efflux systems is an increasingly recognised determinant of both intrinsic and
      acquired multiresistance in these organisms. Homologues of these efflux systems
      are also readily identifiable in the genome sequences of a wide range of Gram
      negative organisms, pathogens and non-pathogens alike, where they probably
      promote efflux-mediated resistance to multiple antimicrobials. Significantly,
      these systems often accommodate biocides, raising the spectre of biocide-mediated
      selection of multiresistance in Gram-negative pathogens. While there is some
      debate as to the natural function of these efflux systems, only some of which are
      inducible by their antimicrobial substrates, their contribution to resistance in
      a variety of pathogens nonetheless makes them reasonable targets for therapeutic
      intervention. Indeed, given the incredible chemical diversity of substrates
      accommodated by these efflux systems, it is likely that many novel or yet to be
      discovered antimicrobials will themselves be efflux substrates and, as such,
      efflux inhibitors may become an important component of Gram-negative
      antimicrobial therapy.

PMID- 14706083
TI  - Clinical and bacteriological efficacy of the ketolide telithromycin against
      isolates of key respiratory pathogens: a pooled analysis of phase III studies.
AB  - A pooled analysis of data from 13 phase III studies of telithromycin in the
      treatment of community-acquired pneumonia, acute exacerbations of chronic
      bronchitis, acute sinusitis or group A beta-haemolytic streptococcal pharyngitis
      and tonsillitis was undertaken. Causative key respiratory tract pathogens
      (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis,
      Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the
      studies from cultures of relevant respiratory samples and tested for their
      susceptibility to telithromycin, penicillin and macrolides (erythromycin A). The
      combined clinical and bacteriological efficacy of telithromycin at the post
      therapy, test-of-cure visit (days 17-24) was assessed in patients from whom a
      microbiologically evaluable pathogen was isolated at entry. More than 98% of key
      respiratory pathogens isolated, including penicillin G- and macrolide
      (erythromycin A)-resistant strains of S. pneumoniae, demonstrated full or
      intermediate susceptibility to telithromycin in vitro at the breakpoints of < or
      = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of
      evaluating the susceptibility of isolates recovered during the clinical trials.
      Treatment with telithromycin 800 mg once-daily for 5, 7 or 7-10 days resulted in
      high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome
      (88.9%), similar to the figures seen with comparator antibacterial agents.
      Clinical cure and eradication rates were good for all key respiratory pathogens,
      including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae.
      The results suggest that telithromycin will provide effective empirical therapy
      for community-acquired upper and lower respiratory tract infections.

PMID- 14706084
TI  - The role of group C and group G streptococci in acute pharyngitis in children.
AB  - Group C streptococci (GCS) and group G beta-haemolytic streptococci (GGS) have
      caused well-documented epidemics of acute pharyngitis in children, but the
      importance of these organisms in causing endemic or sporadic pharyngitis is
      uncertain. The heterogeneity of GCS and GGS may obscure the role of certain
      subtypes, such as the large-colony-forming strains of group C (Streptococcus
      dysgalactiae subsp. equisimilis) or group G, in endemic pharyngitis. For a 1-year
      period, children (aged 6 months to 18 years) (n = 2085) who presented with
      pharyngitis to the children's hospital emergency department and two outpatient
      offices were enrolled in a cross-sectional study to ascertain the role of large
      colony-forming GCS and GGS in acute pharyngitis. Control patients (n = 194) were
      children who presented to the same locations during the same time period with non
      respiratory tract symptoms or to the orthopaedic cast clinic. Throat cultures
      were obtained by a standard reference method, and swabs were plated on Strep
      Selective Agar. Lancefield grouping and species identification was performed on
      all beta-haemolytic isolates. In total, 65 (3%) large-colony-forming GCS and GGS
      strains were obtained from pharyngitis patients, and three (1.5%) were obtained
      from the control group (odds ratio 2.0; 95% confidence interval 0.6-6.1). The low
      isolation rate of large-colony-forming strains of GCS and GGS indicates that even
      if these organisms are associated with acute, sporadic pharyngitis in paediatric
      patients, they represent an unusual pathogen.

PMID- 14706085
TI  - Characterisation of Helicobacter pylori isolates from the north-eastern region of
      Mexico.
AB  - The vacA and cagA genotypes of 50 Helicobacter pylori isolates from patients in
      the north-eastern region of Mexico were characterised by PCR, and the correlation
      between genotypes and different clinical outcomes was investigated. Strains of H.
      pylori that are vacA s1/m1 and cagA positive have previously been associated with
      more severe clinical outcomes, and some studies have shown differences in the
      vacA and cagA genotypes in different geographical regions. The six possible
      combinations of the vacA signal (s) and middle (m) regions were identified in
      this population, and the most frequent genotype was s2/m2. Thirty-two (64%)
      isolates were identified as cagA-positive. The s region was not amplified from
      seven of the cagA-positive isolates, and the m region was not amplified from one
      cagA-negative isolate, indicating that additional subfamilies of s and m
      genotypes may exist. The s1/m1 genotype was associated with cagA-positive strains
      (p < 0.05). No association was found between the vacA and cagA genotypes and
      clinical outcomes.

PMID- 14706086
TI  - Risk factors for systemic emboli in infective endocarditis.
AB  - A retrospective study was undertaken to analyse the risk factors for systemic
      emboli in infective endocarditis. Patients (n = 80; 70% males; mean age 65 years;
      range 20-91 years) with infective endocarditis, as defined by the Duke criteria
      and diagnosed using transoesophageal echocardiography during the period January
      1995 to March 2001, were included. The average time between the start of the
      illness and the beginning of antibiotic treatment was 55 days (range 0-405 days).
      The pathogens identified were streptococci (n = 47), staphylococci (n = 11),
      enterococci (n = 9), and others (n = 4). In nine cases, blood cultures were
      sterile. Thirty patients with at least one embolic episode were compared with 50
      control patients. According to univariate analysis, the main risk factor for
      systemic emboli was the size of the vegetation (12.4 mm vs. 7.8 mm; p = 0.0005).
      The risk of emboli was 57% when the vegetation measured > 10 mm and only 22% when
      it was < 10 mm (p = 0.003). The mobility of the vegetation was also a risk
      factor: 48% if the vegetation was mobile; and 9% if fixed (p = 0.003). Sex, age,
      pathogen, antibiotic treatment, type of valve and the number and position of the
      vegetations were not found to be risk factors. With multivariate analysis, only
      mobility was identified as a risk factor. Overall, mobile vegetations > 10 mm in
      size were associated with an increased risk of embolic episodes in infective
      endocarditis.

PMID- 14706087
TI  - Urinary concentrations and urine ex-vivo effect of mecillinam and
      sulphamethizole.
AB  - Healthy adult volunteers received 1 g of sulphamethizole orally (n = 10) and
      later 400 mg of pivmecillinam (274 mg of mecillinam) (n = 9). All urine was
      collected in defined periods over 24 h, and the drug concentrations in urine were
      determined. For sulphamethizole, the maximum urine concentration for seven
      subjects was reached in 0-3 h, and for the remaining three in 3-6 h. For
      mecillinam, eight of the nine subjects attained a maximum urine concentration in
      0-3 h, after which the concentration declined rapidly for six subjects in 3-6 h.
      Strains of Escherichia coli with different MICs for sulphamethizole and
      mecillinam were exposed to collected urine for 2.5 h and 5 h. The results
      indicated that a sensitive E. coli population should be suppressed by
      sulphamethizole in urine for two-thirds of the time (with 1 g twice-daily) and by
      mecillinam in urine throughout the 24-h period (with 400 mg three times a day).
      There was a slight but significant correlation between the ex-vivo effect (Delta
      log10 CFU/mL) and the log10 concentration/MIC ratio after exposure to
      sulphamethizole for 5 h (r2 = 0.27, p < 0.0001), and a significant correlation
      between the variables with mecillinam (r2 = 0.66, p < 0.0001).

PMID- 14706088
TI  - The use and therapeutic drug monitoring of teicoplanin in the UK.
AB  - Teicoplanin dosage recommendations for specific infections have been modified in
      recent years. However, there was no significant increase in the proportion of pre
      dose concentrations > 20 mg/L between 1994 and 1998 in samples sent for
      teicoplanin assay at the Regional Antimicrobial Reference Laboratory, Bristol,
      UK. A questionnaire on the use of teicoplanin and therapeutic drug monitoring
      (TDM) was sent to all UK National External Quality Assurance Scheme antibiotic
      assay users. Teicoplanin was widely used in the UK, although vancomycin was more
      popular as a choice of glycopeptide. Fewer than 25% recommended teicoplanin TDM
      during routine use, the main reasons being perceived lack of toxicity and lack of
      evidence for the use of teicoplanin TDM. Pre-dose concentrations < 20 mg/L were
      considered appropriate for treatment of bacteraemia caused by methicillin
      resistant Staphylococcus aureus by 53% of those responding. Data sheet advice was
      relied upon more than TDM as an indication of therapeutic dosing. Microbiologists
      who mainly used vancomycin tended to perform more TDM and seek higher serum
      concentrations when using teicoplanin than those who preferentially used
      teicoplanin.

PMID- 14706089
TI  - Isolated anti-HBV core phenotype in anti-HCV-positive patients is associated with
      hepatitis C virus replication.
AB  - Recovery from hepatitis B virus (HBV) infection is associated with the presence
      of antibodies against HBV surface (HBs) antigen and HBV core (HBc) antigen.
      However, anti-HBs antibodies are lost in many cases, and only anti-HBc antibodies
      persist. A higher frequency of the anti-HBc-alone pattern has been demonstrated
      for anti-hepatitis C virus (HCV)-positive patients. In this report, 1126 anti-HCV
      positive/anti-HBc-positive patients were studied, and the role of HCV replication
      in influencing the presence or absence of anti-HBs antibodies was investigated.
      The anti-HBc-alone phenotype was significantly more frequent in HCV-viraemic than
      in HCV-recovered patients. This finding represents new information regarding the
      immunopathogenesis of chronic HCV infection and supports previous data indicating
      impaired humoral immune responses in HCV infection.

PMID- 14706090
TI  - Relationship between ciprofloxacin resistance and extended-spectrum beta
      lactamase production in Escherichia coli and Klebsiella pneumoniae strains.
AB  - Resistance to fluoroquinolones has increased markedly since their introduction.
      Mechanisms of resistance to any antibiotic class might play a role in resistance
      to an unrelated antibiotic class. This study evaluated the relationship between
      extended-spectrum beta-lactamase (ESBL) production and ciprofloxacin resistance
      in Escherichia coli and Klebsiella pneumoniae strains isolated as causative
      agents of urinary tract infection. ESBL-producing strains were significantly more
      frequent among ciprofloxacin-resistant E. coli strains than among ciprofloxacin
      susceptible E. coli strains (p = 0.015), but the difference was not significant
      among K. pneumoniae strains (p = 0.276).

PMID- 14706091
TI  - Quinolone resistance among Escherichia coli strains from community-acquired
      urinary tract infections in Greece.
AB  - Susceptibility data for 10 049 Escherichia coli isolates derived from community
      acquired urinary tract infections in Greece during the period January 2000 to
      June 2002 indicated 8.1% resistance to nalidixic acid and 36% resistance to
      ciprofloxacin. In a sample of 170 E. coli isolates, mutations in gyrA (25
      isolates) and parC (15 isolates) were consistent with the levels of resistance to
      quinolones. Previous exposure to quinolones and underlying chronic disease were
      independent risk factors for infection by quinolone-resistant E. coli strains.

PMID- 14706092
TI  - Preparation of stock solutions of macrolide and ketolide compounds for
      antimicrobial susceptibility tests.
AB  - Stock solutions of telithromycin, ABT-773, azithromycin, clarithromycin,
      erythromycin, roxithromycin and dirithromycin were each prepared with eight
      different combinations of solvents and diluents. Broth microdilution trays were
      then prepared and frozen at -60 degrees C. Standard quality control strains were
      evaluated periodically during a 12-week storage time. There were no significant
      changes in MICs with different solvents and diluents. It was concluded that the
      easiest approach was to dissolve each compound in water with a small volume (<
      2.5 microL/mL) of glacial acetic acid added in a dropwise fashion, followed by
      further dilutions in deionised water.

PMID- 14706093
TI  - Should third-generation cephalosporins be avoided against AmpC-inducible
      Enterobacteriaceae?

PMID- 14706094
TI  - Use of inhaled ampicillin-sulbactam against multiresistant Acinetobacter
      baumannii in bronchial secretions of intensive care unit patients.

PMID- 14706095
TI  - Soft-tissue abscess caused by Salmonella enterica serovar Enteritidis at the site
      of melanoma metastasis.

PMID- 14706096
TI  - The role of endosymbiotic Wolbachia bacteria in filarial disease.
AB  - In this review, we describe the pathogenic role of Wolbachia endosymbiotic
      bacteria in filarial diseases, focusing on the host innate immune responses to
      filarial and Wolbachia products. A description of the host pathogen recognition
      and early inflammatory responses including TLR4-mediated signalling, chemokine
      and cytokine responses and inflammatory cell recruitment is provided from human
      studies and from animal models of filarial disease. Finally, the impact of the
      discovery and characterization of Wolbachia on filarial research and treatment
      programmes is discussed.

PMID- 14706097
TI  - Mycobacterium tuberculosis cell envelope lipids and the host immune response.

PMID- 14706098
TI  - Chlamydia pneumoniae and atherosclerosis.
AB  - Exposure to Chlamydia pneumoniae is extremely common, and respiratory infections
      occur repeatedly among most people. Strong associations exist between C.
      pneumoniae infection and atherosclerosis as demonstrated by: (i) sero
      epidemiological studies showing that patients with cardiovascular disease have
      higher titres of anti-C. pneumoniae antibodies compared with control patients;
      (ii) detection of the organism within atherosclerotic lesions, but not in
      adjacent normal tissue by immunohistochemistry, polymerase chain reaction and
      electron microscopy and by culturing the organism from lesions; and (iii) showing
      that C. pneumoniae can either initiate lesion development or cause exacerbation
      of lesions in rabbit and mouse animal models respectively. The association of
      this organism with atherosclerosis has also provided sufficient impetus to
      conduct a variety of human secondary prevention antibiotic treatment trials. The
      results of these studies have been mixed and, thus far, no clear long-lasting
      benefit has emerged from these types of investigations. Studies of C. pneumoniae
      pathogenesis have shown that the organism can infect many cell types associated
      with both respiratory and cardiovascular sites, including lung epithelium and
      resident alveolar macrophages, circulating monocytes, arterial smooth muscle
      cells and vascular endothelium. Infected cells have been shown to exhibit
      characteristics associated with the development of cardiovascular disease (e.g.
      secretion of proinflammatory cytokines and procoagulants by infected endothelial
      cells and foam cell formation by infected macrophages). More detailed analysis of
      C. pneumoniae pathogenesis has been aided by the availability of genomic sequence
      information. Genomic and proteomic analyses of C. pneumoniae infections in
      relevant cell types will help to define the pathogenic potential of the organism
      in both respiratory and cardiovascular disease.

PMID- 14706099
TI  - Gene expression patterns of epithelial cells modulated by pathogenicity factors
      of Yersinia enterocolitica.
AB  - Epithelial cells express genes whose products signal the presence of pathogenic
      microorganisms to the immune system. Pathogenicity factors of enteric bacteria
      modulate host cell gene expression. Using microarray technology we have profiled
      epithelial cell gene expression upon interaction with Yersinia enterocolitica.
      Yersinia enterocolitica wild-type and isogenic mutant strains were used to
      identify host genes modulated by invasin protein (Inv), which is involved in
      enteroinvasion, and Yersinia outer protein P (YopP) which inhibits innate immune
      responses. Among 22 283 probesets (14,239 unique genes), we found 193 probesets
      (165 genes) to be regulated by Yersinia infection. The majority of these genes
      were induced by Inv, whose recognition leads to expression of NF-kappa B
      regulated factors such as cytokines and adhesion molecules. Yersinia virulence
      plasmid (pYV)-encoded factors counter regulated Inv-induced gene expression.
      Thus, YopP repressed Inv-induced NF-kappa B regulated genes at 2 h post infection
      whereas other pYV-encoded factors repressed host cell genes at 4 and 8 h post
      infection. Chromosomally encoded factors of Yersinia, other than Inv, induced
      expression of genes known to be induced by TGF-beta receptor signalling. These
      genes were also repressed by pYV-encoded factors. Only a few host genes were
      exclusively induced by pYV-encoded factors. We hypothesize that some of these
      genes may contribute to pYV-mediated silencing of host cells. In conclusion, the
      data demonstrates that epithelial cells express a limited number of genes upon
      interaction with enteric Yersinia. Both Inv and YopP appear to modulate gene
      expression in order to subvert epithelial cell functions involved in innate
      immunity.

PMID- 14706100
TI  - Helicobacter pylori vacuolating cytotoxin enters cells, localizes to the
      mitochondria, and induces mitochondrial membrane permeability changes correlated
      to toxin channel activity.
AB  - The Helicobacter pylori vacuolating cytotoxin (VacA) intoxicates mammalian cells
      resulting in reduction of mitochondrial transmembrane potential (Delta Psi m
      reduction) and cytochrome c release, two events consistent with the modulation of
      mitochondrial membrane permeability. We now demonstrate that the entry of VacA
      into cells and the capacity of VacA to form anion-selective channels are both
      essential for Delta Psi m reduction and cytochrome c release. Subsequent to cell
      entry, a substantial fraction of VacA localizes to the mitochondria. Neither
      Delta Psi m reduction nor cytochrome c release within VacA-intoxicated cells
      requires cellular caspase activity. Moreover, VacA cellular activity is not
      sensitive to cyclosporin A, suggesting that VacA does not induce the
      mitochondrial permeability transition as a mechanism for Delta Psi m reduction
      and cytochrome c release. Time-course and dose-response studies indicate that
      Delta Psi m reduction occurs substantially before and at lower concentrations of
      VacA than cytochrome c release. Collectively, these results support a model that
      VacA enters mammalian cells, localizes to the mitochondria, and modulates
      mitochondrial membrane permeability by a mechanism dependent on toxin channel
      activity ultimately resulting in cytochrome c release. This model represents a
      novel mechanism for regulation of a mitochondrial-dependent apoptosis pathway by
      a bacterial toxin.

PMID- 14706101
TI  - Evidence implicating the 5' untranslated region of Listeria monocytogenes actA in
      the regulation of bacterial actin-based motility.
AB  - The ActA protein of Listeria monocytogenes is a major virulence factor, essential
      for the recruitment and polymerization of host actin filaments that lead to
      intracellular motility and cell-to-cell spread of bacteria within the infected
      host. The expression of actA is tightly regulated and is strongly induced only
      when L. monocytogenes is within the host cytosol. Intracellular induction of actA
      expression is mediated through a single promoter element that directs the
      expression of a messenger RNA with a long (150 bp) 5' untranslated region (UTR).
      Deletion of the actA+3 to +130 upstream region was found to result in bacterial
      mutants that were no longer capable of intracellular actin recruitment or cell-to
      cell spread, thus indicating that this region is important for actA expression.
      L. monocytogenes strains that contained smaller deletions (21-23 bp) within the
      actA upstream region demonstrated a range of actA expression levels that
      coincided with the amount of bacterial cell-to-cell spread observed within
      infected monolayers. A correlation appeared to exist between levels of actA
      expression and the ability of L. monocytogenes to transition from uniform actin
      accumulation surrounding individual bacteria (actin clouds) to directional
      assembly and the formation of actin tails. Bacterial mutants containing deletions
      that most significantly altered the predicted secondary structure of the actA
      mRNA 5' UTR had the largest reductions in actA expression. These results suggest
      that the actA 5' UTR is required for maximal ActA synthesis and that a threshold
      level of ActA synthesis must be achieved to promote the transition from bacteria
      associated actin clouds to directional actin assembly and movement.

PMID- 14706102
TI  - Helicobacter pylori toxin VacA is transferred to host cells via a novel contact
      dependent mechanism.
AB  - Helicobacter pylori is the causative agent of peptic ulcer disease. A major
      virulence factor of H. pylori is VacA, a toxin that causes massive vacuolization
      of epithelial cell lines in vitro and gastric epithelial erosion in vivo.
      Although VacA is exported over the outer membrane and is released from the
      bacteria, a portion of the toxin remains associated with the bacterial surface.
      We have found surface-associated toxin to be biologically active and spatially
      organized into distinct toxin-rich domains on the bacterial surface. Upon
      bacterial contact with host cells, toxin clusters are transferred directly from
      the bacterial surface to the host cell surface at the bacteria-cell interface,
      followed by uptake and intoxication. This contact-dependent transfer of VacA
      represents a cost-efficient route for delivery of VacA and potentially other
      bacterial effector molecules to target cells.

PMID- 14706103
TI  - Ehrlichia chaffeensis downregulates surface Toll-like receptors 2/4, CD14 and
      transcription factors PU.1 and inhibits lipopolysaccharide activation of NF-kappa
      B, ERK 1/2 and p38 MAPK in host monocytes.
AB  - Microbial ligands, such as lipopolysaccharide (LPS), activate Toll-like receptors
      (TLRs) of mononuclear phagocytes, thus activating transcription factors including
      NF-kappa B and inducing antimicrobial activity. Ehrlichia chaffeensis, an
      obligatory intramonocytic Gram-negative bacterium, causes human monocytic
      ehrlichiosis. In the present study, we found that E. chaffeensis-infected human
      monocytes became progressively less responsive to Escherichia coli
      lipopolysaccharide (LPS) in activating NF-kappa B and mobilizing ehrlichiacidal
      activities. E. chaffeensis infection caused downregulation of the expression of
      several pattern recognition receptors, such as CD14, TLR2 and TLR4, as revealed
      by flow cytometry and/or reverse transcription polymerase chain reaction
      analysis. Electrophoretic mobility shift assay revealed that the activity of a
      transcription factor PU.1 was also downregulated by E. chaffeensis infection. ERK
      1/2 and p38 MAPK were slightly activated at the early stage of E. chaffeensis
      infection; however, the activations of ERK 1/2 and p38 MAPK by LPS treatment were
      subsequently reduced in E. chaffeensis-infected monocytes compared with those in
      uninfected monocytes. Like E. chaffeensis, the p38 MAPK-specific inhibitor SB
      203580 downregulated PU.1 activity and the expression of TLR2, TLR4 and CD14 in
      human monocytes, suggesting that the inhibition of p38 MAPK by E. chaffeensis is
      involved in the suppression of several downstream signalling pathways. These data
      point to a novel mechanism by which E. chaffeensis can survive by inhibiting
      critical signalling in monocyte activation pathways linked to pattern recognition
      receptors.

PMID- 14706104
TI  - Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane
      lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappa
      B activation.
AB  - Mycoplasmal membrane diacylated lipoproteins not only initiate proinflammatory
      responses through Toll-like receptor (TLR) 2 and TLR6 via the activation of the
      transcriptional factor NF-kappaB, but also initiate apoptotic responses. The aim
      of this study was to clarify the apoptotic machineries. Mycoplasma fermentans
      lipoproteins and a synthetic lipopeptide, MALP-2, showed cytocidal activity
      towards HEK293 cells transfected with a TLR2-encoding plasmid. The activity was
      synergically augmented by co-expression of TLR6, but not by co-expression of
      other TLRs. Under the condition of co-expression of TLR2 and TLR6, the
      lipoproteins could induce maximum NF-kappa B activation and apoptotic cell death
      in the cells 6 h and 24 h after stimulation respectively. Dominant-negative forms
      of MyD88 and FADD, but not IRAK-4, reduced the cytocidal activity of the
      lipoproteins. In addition, both dominant-negative forms also downregulated the
      activation of both NF-kappa B and caspase-8 in the cells. Additionally, the
      cytocidal activity was sufficiently attenuated by a selective inhibitor of p38
      MAPK. These findings suggest that mycoplasmal lipoproteins can trigger TLR2- and
      TLR6-mediated sequential bifurcate responses: NF-kappa B activation as an early
      event, which is partially mediated by MyD88 and FADD; and apoptosis as a later
      event, which is regulated by p38 MAPK as well as by MyD88 and FADD.

PMID- 14706107
TI  - Intravasal microdialysis is superior to intramyocardial microdialysis in
      detecting local ischaemia in experimental porcine myocardial infarction.
AB  - OBJECTIVE: A novel application of microdialysis was studied, where myocardial
      outflow of energy metabolites was monitored by intravasal microdialysis in the
      myocardial venous outflow during ischaemia and reperfusion. These levels where
      related to levels monitored by microdialysis catheters placed intramyocardially.
      METHODS: Microdialysis catheters were introduced into the great cardiac vein
      (GCV), ischaemic myocardium and non-ischaemic myocardium in 10 anaesthetized
      pigs. The left anterior descending coronary artery was occluded for 60 min in
      five pigs and five pigs served as controls. Ischaemia was followed by 120 min of
      reperfusion. Microdialysis samples were analysed for glucose, lactate, pyruvate
      and glycerol. Venous lactate and glucose levels were measured by blood samples
      from the femoral vein. RESULTS: All animals subjected to ischaemia developed
      myocardial infarction. Lactate, lactate/pyruvate ratio and glycerol increased in
      the microdialysis samples from the GCV and the catheter placed in ischaemic
      myocardium while no changes were detected in samples from the catheter placed in
      the non-ischaemic myocardium. CONCLUSION: In this study, we have demonstrated
      that intravasal microdialysis catheters rapidly and reliably detect local
      myocardial ischaemia, while intramyocardially placed microdialysis catheters will
      not show these changes if placed in a non-ischaemic area.

PMID- 14706108
TI  - Rate dependence of mechanically induced electrophysiological changes in right
      ventricle of anaesthetized lambs during pulmonary artery occlusion.
AB  - AIM: Mechanically induced early afterdepolarization (EAD) is morphologically
      similar but different in the mechanisms with drug-induced EAD, which lead to
      arrhythmia. Pacing suppresses the drug-induced EAD and arrhythmia, however the
      effect of pacing on mechanically induced EAD and arrhythmia is not clear. This
      study addressed this issue in right ventricle (RV) of anaesthetized lambs.
      METHODS: Six lambs were anaesthetized, and their hearts exposed. Nine monophasic
      action potential (MAP) electrodes were placed on RV apex, outflow and inflow
      regions, and recorded before, during, and after a 10 s occlusion of pulmonary
      artery at a number of pacing rates. RESULTS: Pacing significantly reduced the
      baseline MAP duration at 90% repolarization (MAPD90), decreased the reduction of
      MAPD at early repolarization at the peak of occlusion. Nonetheless, the
      percentage of reduction was not significantly different among them. Pacing was
      able to reduce the frequencies, size of mechanically induced EADs. MAPD90 at the
      peak of occlusion was all shortened during pacing rather than some lengthened at
      intrinsic rate. Therefore, the dispersion of MAPD90 at the peak of occlusion
      reduced from 86 +/- 6 ms at intrinsic rate to 42 +/- 4 ms at 120 beats min-1, 38
      +/- 3 ms at 150 beats min-1 and 26 +/- 3 ms at 170 beats min-1. Ultimately,
      pacing reduced/suppressed mechanically induced premature ventricular beats. These
      alterations were inversely related to heart rates. CONCLUSION: Pacing
      reduces/suppresses both stretch-induced EADs and arrhythmia. These modulations
      are remarkably similar to those on other EADs by the pacing.

PMID- 14706109
TI  - Myocardial ferritin content is closely related to the degree of ischaemia.
AB  - AIM: Ferritin acts as an iron scavenger and thereby may reduce iron catalysed
      oxygen radical production during reperfusion injury. We tested the hypothesis
      that the myocardial ferritin concentration is enhanced during ischaemia in
      proportion to the blood flow reduction. METHODS: In 10 anaesthetized, open chest
      Beagle dogs (six controls and four with 60 min coronary occlusion) regional
      myocardial blood flow (RMBF) was measured with the tracer microsphere technique
      and ferritin was determined in samples with an average mass of 125 mg (124-256
      samples per heart). RESULTS: Under physiological conditions heart rate was 88 +/-
      12 bpm, mean aortic pressure 98 +/- 8 mmHg, and RMBF 0.99 +/- 0.33 mL min-1 g-1.
      Data did not differ between experimental groups, P > 0.05. In the control group
      regional myocardial ferritin concentration averaged 11.76 +/- 3.54 ng mg-1
      protein and exhibited a significant blood flow independent heterogeneity
      (CV(biol) = 0.27). However, between low and high flow areas (relative flow <0.5
      and >1.5 times the average RMBF, respectively) no significant difference in
      ferritin was found, P > 0.05. In four experiments, in which regional blood flow
      was reduced by 40% to 0.60 +/- 0.23 mL min-1 g-1, regional ferritin content was
      significantly higher as compared with the control group 27.95 +/- 6.16 vs. 11.76
      +/- 3.54 ng mg-1 protein, respectively. An inverse relationship was observed
      between ferritin and RMBF, r = -0.61, P < 0.001. Thus, a reduction of RMBF of
      >80% was associated with a 2.75-fold increase of the average ferritin content.
      Between subepicardium and subendocardium no significant difference in ferritin
      content was observed, neither in the control group nor in the group with induced
      ischaemia. Regions with control low and high flow responded similarly to the
      coronary constriction with regard to the local ferritin concentration: 27.88 +/-
      15.22 vs. 30.10 +/- 14.91 ng mg-1, P > 0.05, respectively. A data analysis using
      Baye's theorem indicated that sensitivities were 0.28 and 0.94 for average flow
      reductions of 5 and 93%. In additional in vitro measurements (ischaemic
      incubation at 37 degrees C) myocardial ferritin content increased almost linearly
      within the first 60 min of incubation and thereafter remained unchanged.
      CONCLUSIONS: (1). Local physiological ferritin content in myocardium is
      heterogeneous and unrelated to control myocardial blood flow. (2). Ischaemia
      results in an enhanced ferritin content in relation to the degree of ischaemia.
      (3). The increase of myocardial ferritin requires a severe degree of ischaemia.

PMID- 14706110
TI  - Effect of anaesthetic and rat strain on heart rate responses to simulated
      haemorrhage.
AB  - AIM AND METHODS: Haemorrhage is characterized by two distinct responses,
      sympathoexcitation that evokes tachycardia and supports blood pressure, followed
      by sympathoinhibition contributing to bradycardia and hypotension. It has been
      shown that anaesthetics alter the response to haemorrhage and we hypothesized
      that rat strain may also influence the response. We investigated the effect of
      simulated haemorrhage on heart rate (HR) responses in three strains of conscious
      rats, and the effect of three common anaesthetics, by comparing HR responses
      under anaesthesia to the conscious response. Haemorrhage was simulated by
      constricting the inferior vena cava. We demonstrate differential effects of
      anaesthetics, including both maintenance and elimination of HR responses to
      haemorrhage depending on anaesthetic. RESULTS: We also show that both phases of
      the HR response differ in different conscious rat strains, and we have
      demonstrated a transient increase in HR during the decompensatory phase of
      haemorrhage, a novel 'second HR peak' with advanced hypotension. CONCLUSION: Both
      rat strain and anaesthetic influence HR responses to haemorrhage, and some
      anaesthetics appear less suitable than others for studies of haemodynamic
      responses in rats. There was evidence of an additional compensatory mechanism
      that operates at advanced levels of hypotension in the rat.

PMID- 14706111
TI  - Reopening of L-type calcium channels in human ventricular myocytes during applied
      epicardial action potentials.
AB  - AIMS: Present study was performed to compare the dynamics of human L-type calcium
      current (ICa,L) flowing during rectangular voltage pulses, voltage ramps, and
      action potentials (APs) recorded from epicardiac and endocardiac canine
      ventricular cells. METHODS: ICa,L was recorded in single myocytes isolated from
      undiseased human hearts using the whole cell voltage clamp technique. RESULTS:
      The decay of ICa,L was monotonic when using rectangular pulses or endocardial APs
      as voltage commands, whereas the current became double-peaked (displaying a
      second rise and fall) during epicardial (EPI) APs or voltage ramps used to mimic
      EPI APs. These ICa,L profiles were associated with single-hooked and double
      hooked phase-plane trajectories, respectively. No sustained current was observed
      during the AP commands. Kinetics of deactivation and recovery from inactivation
      of human ICa,L were determined using twin-pulse voltage protocols and voltage
      ramps, and the results were similar to those obtained previously in canine cells
      under identical experimental conditions. CONCLUSIONS: ICa,L can inactivate
      partially before and deactivate during the phase-1 repolarization of the
      epicardiac AP, and reopening of these channels seems to be associated with
      formation of the dome.

PMID- 14706112
TI  - Quantification of alpha-subunit isoforms of Na,K-ATPase in rat resistance
      vessels.
AB  - AIM: Rat mesenteric resistance vessels (RV) were characterized with respect to
      concentration of individual alpha-subunit isoforms of Na,K-ATPase. METHODS: Total
      vessel homogenates were used to avoid any loss or subfractionation of membranes.
      They were applied to sodium dodecyl sulphate gels and, for calibration, in
      parallel lanes were run purified rat Na,K-ATPase preparations with known isoform
      distribution and content. The capacity per mg protein for Na+-dependent 32P
      phosphorylation of Na,K-ATPase isolated from rat kidney was used for alpha1
      calibration and that for high-affinity (3H)ouabain binding of Na,K-ATPase
      isolated from rat brain was used for (alpha2 + alpha3) calibration. Western blots
      containing homogenate proteins and reference enzyme were incubated with isoform
      specific antibodies and radiolabelled secondary antibodies. The signals from
      adjacent alpha spots were used for qualitative and quantitative characterization
      of rat vessels. RESULTS: A concentration of 100.7 +/- 14.4 pmol (n = 11) per g
      wet weight of the alpha1-isoform containing Na,K-ATPase was found in RV from 12
      14-week rats. A much lower and more unreliable content of alpha2- and alpha3
      isoforms was found. These ouabain-sensitive isoforms seem to represent a maximum
      of 5-10% each compared with the ouabain-insensitive rat alpha1-isoform.
      CONCLUSIONS: The isoform pattern in RV, in which the isoform with
      high/intermediate Na+-affinity is the absolutely dominating one representing
      nearly all sodium pumps in this tissue, is very different from that seen in rat
      skeletal muscles. Due to the high content of the ouabain-insensitive alpha1
      isoform in rat RV this species would seem a less relevant model in studies
      addressing a role of cardiac glycosides and putative endogenous ouabain-like
      factors in hypertension.

PMID- 14706113
TI  - Muscle blood flow in response to concentric muscular activity vs passive venous
      compression.
AB  - AIM: To measure muscle blood flow (MBF) using photoplethysmography (PPG)
      following concentric muscular activity of the leg (active treatment) or passive
      venous compression (passive treatment) with or without venous obstruction.
      METHODS: In study A, blood flow in the anterior tibial muscle was measured in 15
      healthy subjects with a mean age of 30 years. In study B, blood flow in the
      gastrocnemius muscle was measured in nine healthy subjects with a mean age of 34
      years. Subjects performed concentric muscular activity in one leg. Passive venous
      compression by a venous foot pump was applied in the contralateral leg. RESULTS:
      MBF increased significantly following concentric muscular activity, but not
      following passive venous compression. MBF decreased in both legs when venous
      obstruction, induced by a thigh tourniquet, was applied. However, MBF was
      significantly higher following concentric muscular activity than passive venous
      compression. CONCLUSION: We conclude that concentric muscular activity produces
      higher MBF values than passive venous compression.

PMID- 14706114
TI  - Sweating responses during activation of the muscle metaboreflex in humans is
      altered by time of day.
AB  - AIM: The aim of the present study was to test for a time-of-day effect on
      sweating responses to activation of the muscle metaboreflex. METHODS: Eight male
      subjects each participated in two exercise sessions, one in the morning and one
      in the evening. Within each session there were two 60-s bouts of isometric
      handgrip (IHG) exercise at 50% maximal voluntary contraction. Prior to IHG, whole
      body warming by a water-perfused suit initiated mild sweating. The first bout of
      IHG exercise began at 06.00 hours (am) and 18.00 hours (pm). Blood circulation to
      the forearm was occluded for 120 s, beginning 5 s before the end of the second
      bout of IHG to activate the muscle metaboreflex. RESULTS: During both bouts of
      exercise, sweating rate (SR) on both the chest and right forearm significantly
      increased from the pre-exercise period in both am and pm sessions. SR rapidly
      decreased during first minute of recovery after the first bout of IHG exercise.
      However, during post-exercise ischaemia (PEI) after the second bout of IHG
      exercise, SR was maintained significantly above the pre-exercise level only in
      the pm session. The increases in SR on the chest and right forearm during PEI
      were significantly greater in the pm, than in the am, session. However, SR of the
      palm was not maintained during PEI. CONCLUSIONS: We conclude that under mild
      hyperthermic conditions, the sweating response in non-glabrous skin to activation
      of the muscle metaboreflex exhibits a time-of-day effect.

PMID- 14706115
TI  - Stimulation of HSP72 expression following ATP depletion and short-term exercise
      training in fast-twitch muscle.
AB  - AIM: Previous data have reported increases in HSP72 expression in skeletal
      muscles after endurance training but the physiological and biochemical signals
      that induce HSP72 accumulation remain largely unknown. In this study, we tested
      the hypothesis that energy status is a key regulatory event for HSP72
      accumulation in skeletal muscles. METHODS: Reduction of high-energy phosphate
      levels was induced by supplementation with a creatine analogue, beta
      guanidinopropionic acid (GPA) for 3 weeks while control rats received distilled
      water in the same conditions. Half of the animals were kept sedentary while the
      others were submitted to a short-term (2 weeks) training program on a treadmill
      (30 m min-1, 0% slope; 50-70 min day-1). RESULTS: GPA supplementation resulted in
      a large drop ( approximately 50%) in adenosine triphosphate (ATP) level in both
      fast and slow muscles whether the animals were trained or remained sedentary.
      HSP72 level did not change with GPA alone, but the training-induced increase in
      HSP72 level was strongly enhanced by superimposition of GPA diet in fast but not
      in slow skeletal muscles. The changes in HSP72 level were not linked to changes
      in fibre typology and/or mitochondrial capacities. CONCLUSIONS: The results of
      the present investigation indicate that levels of high-energy phosphate per se do
      not play a direct role in determining HSP72 level in skeletal muscles. However,
      during superimposition of training to GPA, then the adaptive strategy of fast
      twitch muscle (e.g. plantaris) seems to be directed towards appearance of some
      properties of red, oxidative fibres (increase in oxidative capacities and HSP72
      level).

PMID- 14706116
TI  - Different time course of changes in sarcoplasmic reticulum and myosin isoforms in
      rat soleus muscle at early stage of hyperthyroidism.
AB  - AIMS AND METHODS: We studied changes in the expression of myosin and sarcoplasmic
      reticulum (SR) Ca2+-ATPase (SERCA) and in Ca2+ uptake and release rates by the SR
      in rat slow-twitch soleus muscles treated with thyroid hormone (3,5,3'-triiodo-l
      thyronine, T3) for 1, 3, 7 and 21 days. RESULTS: The content of fast SR Ca2+
      ATPase isoform SERCA1a protein significantly increased as early as 3 days of T3
      treatment, while a rise in fast myosin heavy chain isoforms was found only 21
      days after the onset of T3 administration. T3-induced slow-to-fast transitions
      were much less pronounced in myosin light chain than in myosin heavy chain.
      Moreover, in vitro measurements of SR Ca2+-handling capacity with indo-1
      indicated that increases in uptake rate preceded those of release rate (7 vs. 21
      days). CONCLUSION: These data suggest that changes in the myosin and SERCA
      expressions seem not to occur in a coordinated manner at the early stage of
      hyperthyroidism and that intervention with T3 may temporarily produce slow-twitch
      type I fibres which contain, in addition to slow SERCA2a isoform, the appreciable
      amounts of fast SERCA1a isoform. Moreover, it is speculated that some fibres in
      the hyperthyroid soleus muscles may temporarily acquire unique contractile
      properties distinct from normal fast and slow fibres.

PMID- 14706117
TI  - Muscle hypertrophy following 5-week resistance training using a non-gravity
      dependent exercise system.
AB  - AIM: The efficacy of a mechanical, gravity-independent resistance exercise (RE)
      system to induce strength gains and muscle hypertrophy was validated. Designed
      for space crew in orbit, this technique offers resistance during coupled
      concentric and eccentric actions by utilizing the inertia of a rotating
      flywheel(s), set in motion by the trainee. METHODS: Ten middle-aged (30-53 years)
      men and women performed four sets of seven maximal, unilateral (left limb) knee
      extensions two or three times weekly for 5 weeks. Knee extensor force and
      electromyographic (EMG) activity of the three superficial quadriceps muscles were
      measured before and after this intervention. In addition, with the use of
      magnetic resonance imaging (MRI), volume of individual knee extensor and ankle
      plantar flexor muscles was assessed. RESULTS: Over the 12 training sessions, the
      average concentric (CON) and eccentric (ECC) force generated during exercise
      increased by 11% (P < 0.05). Likewise, maximal isometric strength (maximal
      voluntary contraction, MVC) at 90 and 120 degrees knee angle increased by (P <
      0.05) 11 and 12% respectively, after training. Neither individual quadriceps
      muscle showed a change (P > 0.05) in maximal integrated EMG (iEMG) activity.
      Quadriceps muscle volume increased by 6.1% (P < 0.05). Although the magnitude of
      response varied, all individual quadriceps muscles showed increased (P < 0.05)
      volume after training. As expected, ankle plantar flexor volume of the trained
      limb was unchanged (P > 0.05). Likewise, MVC, CON and ECC force, iEMG and knee
      extensor and plantar flexor muscle volume were unaltered (P > 0.05) in the right,
      non-trained limb. CONCLUSION: The results of this study show that the present RE
      regimen produces marked muscle hypertrophy and important increases in maximal
      voluntary strength and appears equally effective as RE paradigms using gravity
      dependent weights, in this regard.

PMID- 14706118
TI  - Stretch reflex excitability of the anti-gravity ankle extensor muscle in elderly
      humans.
AB  - AIM: To examine whether the stretch reflex excitability of the soleus muscle
      changes with age, stretch reflexes at rest (REST) and during weak voluntary
      contractions (ACT) were elicited in 18 older and 14 younger subjects. METHOD: The
      amplitude of the stretch reflex responses and gain, defined as the gradient of
      the regression line for the relation between stretch reflex responses against the
      angular velocity of the applied perturbation, were evaluated in each short
      latency (M1) and two long-latency components (M2 and M3). RESULTS: It was found
      that in the older group, both the amplitude and gain of the M1 component did not
      change from the REST to the ACT conditions, whereas in the younger group both
      variables significantly increased from the REST to ACT conditions. The latency of
      the M1 component was significantly shorter under the REST condition (older vs.
      younger: 51.8 +/- 7.37 vs. 55.1 +/- 8.69 ms), while no group differences were
      found in those variables under the ACT condition, suggesting that the muscle
      tendon complexes of SOL muscles of the older subjects were less elastic and had
      less slack, probably due to age-related histochemical alterations. Further, the
      Hoffman reflex (H-reflex), elicited during the REST condition in 10 older and 11
      younger subjects showed no significant differences, suggesting that the soleus
      motoneuron response to the Ia input was comparable between the two subject
      groups. CONCLUSION: The histochemical alterations occurring with the ageing
      process might augment the short-latency stretch reflex in the SOL muscle without
      enhancement of motoneuronal excitability, and this effect might be masked when
      the muscle is voluntarily activated.

PMID- 14706119
TI  - The reporting of theoretical health risks by the media: Canadian newspaper
      reporting of potential blood transmission of Creutzfeldt-Jakob disease.
AB  - BACKGROUND: The media play an important role at the interface of science and
      policy by communicating scientific information to the public and policy makers.
      In issues of theoretical risk, in which there is scientific uncertainty, the
      media's role as disseminators of information is particularly important due to the
      potential to influence public perception of the severity of the risk. In this
      article we describe how the Canadian print media reported the theoretical risk of
      blood transmission of Creutzfeldt-Jakob disease (CJD). METHODS: We searched 3
      newspaper databases for articles published by 6 major Canadian daily newspapers
      between January 1990 and December 1999. We identified all articles relating to
      blood transmission of CJD. In duplicate we extracted information from the
      articles and entered the information into a qualitative software program. We
      compared the observations obtained from this content analysis with information
      obtained from a previous policy analysis examining the Canadian blood system's
      decision-making concerning the potential transfusion transmission of CJD.
      RESULTS: Our search identified 245 relevant articles. We observed that newspapers
      in one instance accelerated a policy decision, which had important resource and
      health implication, by communicating information on risk to the public. We also
      observed that newspapers primarily relied upon expert opinion (47 articles) as
      opposed to published medical evidence (28 articles) when communicating risk
      information. Journalists we interviewed described the challenges of balancing
      their responsibility to raise awareness of potential health threats with not
      unnecessarily arousing fear amongst the public. CONCLUSIONS: Based on our
      findings we recommend that journalists report information from both expert
      opinion sources and from published studies when communicating information on
      risk. We also recommend researchers work more closely with journalists to assist
      them in identifying and appraising relevant scientific information on risk.

PMID- 14706120
TI  - Loss of circadian rhythm of blood pressure following acute stroke.
AB  - BACKGROUND: Epidemiology of acute stroke in developing countries differs from
      that in the developed world, for example, the age at stroke, risk factors,
      subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and
      prognostic indicator in patients with stroke in all communities. The risk of
      stroke is directly related to elevations of blood pressure. A number of clinical
      studies have shown that the control of hypertension leads to a reduction in the
      incidence of stroke in a community. However there is still considerable
      controversy surrounds the changes in blood pressure in various subtypes of
      strokes and problem of management of elevated BP after stroke. We studied the
      circadian rhythm of blood pressure in patients following acute stroke. METHODS:
      To study the circadian rhythm of blood pressure, fifty consecutive patients with
      an acute stroke who were admitted to medical emergency within 120 hours of onset
      were included in the study. After a detailed history and clinical examination, a
      continuous blood pressure monitor (Spacelab 90207) was attached on the side
      ipsilateral to intracranial lesion (unaffected arm). The blood pressure was
      recorded for 24 hours at 15 minutes interval during daytime (6.00 am-6.00 pm) and
      20 minutes interval overnight (6 pm to 6 am). RESULTS: Risk factors for stroke in
      50 patients included hypertension in 31(62%), diabetes mellitus in 4 (8%),
      smoking in 13 (26%) and previous history of transient ischemic attack in 7 (14%)
      patients. Mean systolic pressure and diastolic pressure at admission were higher
      in patients with hemorrhagic stroke -29 patients (177 +/- 24 mmHg and 105 +/- 19
      mmHg respectively) compared to patients with ischemic strokes-21 patients (150 +/
      36 mm Hg and 89 +/- 18 mm Hg respectively, p value <0.01 in both comparisons).
      The normal diurnal variation in blood pressure (night time dipping of more than
      10%) was abolished in 44 (88%) of patients. Out of 44 nondippers, 29 patients
      showed reverse dipping i.e. rise of BP during night time compared to day time
      levels. None of the risk factors, clinical or laboratory variables, type of
      stroke or blood pressure changes differed significantly between these two groups.
      CONCLUSIONS: Therefore, we showed a pathologically reduced or abolished circadian
      BP variation after stroke. Absence of normal dipping results in a higher 24 hour
      blood pressure load and may have more target organ damage than those with normal
      diurnal variation of blood pressure.

PMID- 14706121
TI  - PyEvolve: a toolkit for statistical modelling of molecular evolution.
AB  - BACKGROUND: Examining the distribution of variation has proven an extremely
      profitable technique in the effort to identify sequences of biological
      significance. Most approaches in the field, however, evaluate only the conserved
      portions of sequences - ignoring the biological significance of sequence
      differences. A suite of sophisticated likelihood based statistical models from
      the field of molecular evolution provides the basis for extracting the
      information from the full distribution of sequence variation. The number of
      different problems to which phylogeny-based maximum likelihood calculations can
      be applied is extensive. Available software packages that can perform likelihood
      calculations suffer from a lack of flexibility and scalability, or employ error
      prone approaches to model parameterisation. RESULTS: Here we describe the
      implementation of PyEvolve, a toolkit for the application of existing, and
      development of new, statistical methods for molecular evolution. We present the
      object architecture and design schema of PyEvolve, which includes an adaptable
      multi-level parallelisation schema. The approach for defining new methods is
      illustrated by implementing a novel dinucleotide model of substitution that
      includes a parameter for mutation of methylated CpG's, which required 8 lines of
      standard Python code to define. Benchmarking was performed using either a
      dinucleotide or codon substitution model applied to an alignment of BRCA1
      sequences from 20 mammals, or a 10 species subset. Up to five-fold parallel
      performance gains over serial were recorded. Compared to leading alternative
      software, PyEvolve exhibited significantly better real world performance for
      parameter rich models with a large data set, reducing the time required for
      optimisation from approximately 10 days to approximately 6 hours. CONCLUSION:
      PyEvolve provides flexible functionality that can be used either for statistical
      modelling of molecular evolution, or the development of new methods in the field.
      The toolkit can be used interactively or by writing and executing scripts. The
      toolkit uses efficient processes for specifying the parameterisation of
      statistical models, and implements numerous optimisations that make highly
      parameter rich likelihood functions solvable within hours on multi-cpu hardware.
      PyEvolve can be readily adapted in response to changing computational demands and
      hardware configurations to maximise performance. PyEvolve is released under the
      GPL and can be downloaded from http://cbis.anu.edu.au/software.

PMID- 14706122
TI  - Testing the feasibility of implementation of clinical practice guidelines in long
      term care facilities.
AB  - OBJECTIVES: The purpose of this study was to explore the feasibility of
      implementing two specific Clinical Practice Guidelines (CPGs), Pain Management
      and Falls and Fall Risk, developed by the American Medical Directors Association.
      DESIGN: This study used a combined quantitative and qualitative design using a
      single-group repeated-measures design for the quantitative component. SETTING:
      The study was done in 23 long-term care facilities in Maryland. PARTICIPANTS: Of
      40 facilities that participated in a training program for CPG implementation, 32
      were interested in implementing CPGs and 23 volunteered to participate in the
      study. Evaluation of the Falls CPG was based on 127 randomly selected cases
      preimplementation and 119 randomly selected cases postimplementation from the 23
      facilities. Evaluation of the Pain CPG included 64 randomly selected cases
      preimplementation and 74 randomly selected cases postimplementation from the 23
      facilities. Qualitative data was obtained from 20 of the directors of nursing.
      INTERVENTION: Thirteen of the facilities implement-ed the Falls CPG, 10
      facilities implemented the Pain CPG, and eight facilities implemented both CPGs.
      MEASUREMENTS: Process indicators of CPG implementation were used in this study.
      Process indicators included five measurable items that were indicative of CPG
      implementation such as evidence of a pain assessment. RESULTS: Less than half
      (45%) of the original 40 facilities actually implemented at least one of the
      CPGs. Based on process indicators in those facilities that did implement the
      CPGs, there was evidence that the guidelines were being implemented. Qualitative
      data led to the development of four major themes: challenges to implementation,
      benefits of implementation, process recommendations, and recommendations for
      changes in the CPGs. CONCLUSION: The study provides some support for the
      feasibility of CPG implementation in facilities that voluntarily attempted to
      implement the guidelines. In addition, the findings provide some useful
      suggestions for how to facilitate the implementation process.

PMID- 14706123
TI  - Utilization of nurse practitioners in long-term care: findings and implications
      of a national survey.
AB  - OBJECTIVES: The objective of this study was to determine the national practice
      patterns of nurse practitioners (NPs) providing care in long-term care (LTC)
      facilities, including the number and characteristics of LTC facilities that use
      NPs for any portion of care to residents, NP activities, and employment
      arrangements between NPs, physicians, and facilities. DESIGN: Mailed survey.
      PARTICIPANTS: Participants included all physicians who are members of the
      American Medical Directors Association (AMDA). MEASUREMENT: The survey instrument
      was constructed to obtain information in the following six domains: (1) the
      number of LTC facilities that have NPs involved in providing care; (2) the number
      of NPs engaged in care at these facilities; (3) the types of employment/financial
      arrangements between NPs and LTC facilities; (4) the types of services provided
      by the NPs; (5) the effectiveness of the NPs as perceived by the medical
      directors; and (6) the perceived future demand for NPs in LTC. RESULTS: Of a
      total of 870 respondents (response rate 19%), 546 respondents (63%) reported the
      involvement of NPs in the care of residents in their facilities. In total,
      respondents identified 1160 NPs involved in care, with a median of two NPs per
      responding facility (range, 1-10). Respondents reported that NPs make sick/urgent
      resident visits (96%), provide preventive care to long-stay residents (88%), and
      perform alternating required regulatory 30/60 (88%), hospice care (80%), and
      wound care (78%). Significant variations in practice patterns were found between
      NPs employed by a LTC facility (19% of respondents) as compared with those NPs
      employed in other arrangements. Large majorities of medical directors stated that
      NPs are particularly effective in maintaining physician satisfaction (90%),
      resident satisfaction (87%), and family satisfaction (85%). An additional 34% of
      the respondents projected an increased need for NPs in nursing homes in the
      future. CONCLUSION: NPs involved in LTC are more likely to be involved in the
      care of residents in the nation's larger (>100-bed) LTC facilities. The
      substantial number and types of services provided by these NPs, coupled with the
      high resident, family, and physician satisfaction with their services, suggests
      the need for educational, policy, and reimbursement strategies to encourage the
      further involvement of NPs in the care of residents in nursing homes.

PMID- 14706124
TI  - A comparative study of nursing home resident outcomes between care provided by
      nurse practitioners/physicians versus physicians only.
AB  - OBJECTIVES: The objective of this study was to determine if outcomes of care for
      nursing home residents differ between two groups of providers: nurse
      practitioners/physicians and physicians only. DESIGN: We conducted a
      retrospective chart review covering the 12-month period from September 1, 1997,
      until August 31, 1998. SETTING: We studied eight nursing homes in central Texas.
      PARTICIPANTS: Two hundred three residents were randomly selected who resided in
      one of the eight nursing homes during the specified time period. STATISTICAL
      ANALYSIS: We used chi-squared or Fisher exact test for comparisons of percent and
      Student t test for comparison of means; comparisons were made with both the FREQ
      procedure and the univariate procedure. RESULTS: Acute visits were significantly
      higher for the nurse practitioner/physician team (3.0 +/- 2.4) versus the
      physician-only group (1.2 +/- 1.5). The nurse practitioner/physician group
      treated significantly more eye, ear, nose, and throat and dermatologic diagnoses
      than the physician-only group. Emergency department visits, emergency department
      costs, hospitalizations, length of stay, hospital costs, performance of mandated
      progress visits, and performance of annual history and physicals did not show
      significant differences between the two groups. CONCLUSION: The level of care
      provided for patients by the two groups of providers was basically the same and
      of similar quality; however, the nurse practitioner/physician group patients were
      seen more often. Increased visits by nurse practitioners are assumed to result in
      time and cost savings for physicians and improved access to care for patients.

PMID- 14706125
TI  - The effect of megestrol acetate on oral food and fluid intake in nursing home
      residents: a pilot study.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of megestrol
      acetate (Megace OS; Bristol-Myers Squibb, Princeton, NJ) on the oral food and
      fluid intake of nursing home (NH) residents under two conditions: usual NH care
      and optimal mealtime feeding assistance. DESIGN AND SETTING: We conducted a
      prospective, preliminary trial in four NHs. PARTICIPANTS: Participants (n = 17)
      were recruited from a larger study designed to assess nutritional care quality.
      Eligibility for the Megace OS trial required participants to consistently eat
      less than 75% of most meals under both usual NH care and optimal feeding
      assistance conditions at baseline. INTERVENTION: Megace OS, an oral liquid
      suspension of megestrol acetate, was given daily in a 400-mg dose for 63 days.
      MEASUREMENTS: Each participant's oral food and fluid intake was monitored weekly
      for 1 day (three meals) during which research staff conducted direct observations
      of usual NH care (weeks 1, 3, and 5 and day 63) or provided optimal feeding
      assistance (weeks 2, 4, and 6). Average total percent intake was compared from
      baseline across the assessment weeks of the trial under the two mealtime care
      conditions. RESULTS: Megace OS had a significant effect on oral food and fluid
      intake only under the optimal mealtime feeding assistance condition, in which
      average total percent eaten increased from 50% (+/- 15%) at baseline to 63% (+/-
      14%) post-63 days of the trial. There was no change in participants' oral food
      and fluid intake under the usual NH care condition (average total percent intake
      at baseline 43% +/- 12% vs. 43% +/- 20% post-63 days). CONCLUSION: The results of
      this preliminary study suggest that Megace OS is not an effective nutritional
      intervention to increase oral intake under usual NH care conditions, which is
      often characterized by inadequate feeding assistance. However, Megace OS in
      combination with optimal mealtime feeding assistance does significantly increase
      oral intake in a frail NH sample at high risk for weight loss.

PMID- 14706126
TI  - Corticosteroids and chronic obstructive pulmonary disease in the nursing home.

PMID- 14706127
TI  - Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a
      geriatric population in the United States.
AB  - OBJECTIVES: The objective of this study was to investigate risk of diabetes among
      elderly patients during treatment with antipsychotic medications. DESIGN: We
      conducted a longitudinal, retrospective study assessing the incidence of new
      prescription claims for antihyperglycemic agents during antipsychotic therapy.
      SETTING: Prescription claims from the AdvancePCS claim database were followed for
      6 to 9 months. PARTICIPANTS: Study participants consisted of patients in the
      United States aged 60+ and receiving antipsychotic monotherapy. The following
      cohorts were studied: an elderly reference population (no antipsychotics: n =
      1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658);
      all patients receiving any conventional antipsychotic monotherapy (n = 11,546),
      clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and
      risperidone (n = 12,244), and all patients receiving any atypical antipsychotic
      monotherapy (n = 19,407). MEASUREMENTS: We used Cox proportional hazards
      regression to determine the risk ratio of diabetes for antipsychotic cohorts
      relative to the reference population. Covariates included sex and exposure
      duration. RESULTS: New antihyperglycemic prescription rates were higher in each
      antipsychotic cohort than in the reference population. Overall rates were no
      different between atypical and conventional antipsychotic cohorts. Among
      individual antipsychotic cohorts, rates were highest among patients treated with
      thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine
      (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and
      risperidone. Among atypical cohorts, only risperidone users had a significantly
      higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions
      about clozapine were hampered by the low number of patients. CONCLUSION: These
      data suggest that diabetes risk is elevated among elderly patients receiving
      antipsychotic treatment. However, causality remains to be demonstrated. As a
      group, the risk for atypical antipsychotic users was not significantly different
      than for users of conventional antipsychotics.

PMID- 14706128
TI  - The appropriate use of chemotherapy in older adults with colon cancer.

PMID- 14706129
TI  - CPT coding for hospice in long-term care.

PMID- 14706130
TI  - Developing innovative models to translate guidelines into practice.

PMID- 14706131
TI  - Addressing the challenges to improve long-term care.

PMID- 14706132
TI  - What has SARS taught us about infection control in nursing homes?

PMID- 14706134
TI  - [Human placenta derived adherent cells support in vitro expansion of umbilical
      cord blood CD34+ cells].
AB  - The objective of this study was to elucidate the effect of human placenta
      adherent cells (hPDAC) on expansion of human umbilical cord blood CD34(+) cells
      in vitro. hPDAC was isolated and characterized in human placenta tissue by using
      enzyme-digesting method and flow cytometry. A co-culture system was established
      with hPDAC and cord blood CD34(+) cells. The CD34(+) cells were cultured in
      different culture systems with different combinations of hPDAC and SCF, IL-3, IL
      6 and FL. The number of total nucleated cells, CFC and CD34(+) cells were
      repeatedly counted in culture for 4 weeks. The results showed that the hPDAC
      displayed fibroblast-like morphology, and were positive for CD29, CD44, CD166,
      HLA-ABC and UEA-1, and negative for CD34, CD45 and HLA-DR. Functionally, ex vivo
      expansion of CD34(+) cells on feeder layer of placental adherent cells was
      significantly higher than that no feeder layer group. SCF + IL-3 + IL-6 + FL +
      hPDAC manifested the most potent combination, with the number of total nucleated
      cells increasing by (126.0 +/- 6.7)-fold, progenitor cells (CFC) (49.8 +/- 1.7)
      fold and CD34(+) cells (8.3 +/- 1.65)-fold. It is concluded that placental
      adherent cells could support hematopoiesis in vitro and work as a suitable feeder
      layer for cord blood stem/progenitor cell expansion.

PMID- 14706135
TI  - [The growth characteristics of mesenchymal stem/progenitor cells in human
      umbilical cord blood].
AB  - This study was done for investigating the frequency and proliferative feature of
      mesenchymal stem/progenitor cells (MSPC) in human umbilical cord blood (CB) and
      for searching a new seed cell for tissue engineering. Mononuclear cells was
      separated by Ficoll-Hypaque from cord blood and suspended in DMEM culture medium
      supplemented by 2% fetal bovine serum. The adherent CB cells were cultured and
      expanded at same medium. The results showed that the frequency of CB-MSPC was 0.5
      x 10(-6) [(0.2 - 0.8) x 10(-6)]. The CB-MSPC showed a fibroblast-like morphology
      and retained their morphological feature at least after 20 sub-passages, and
      could extensively be expanded by about 1.3 x 10(7) times as much. The conclusion
      is that low serum DMEM culture could maintain the proliferation and
      differentiation potential of CB-MSPC. CB-MSPC might be a favorable seed cell for
      tissue engineering and regeneration.

PMID- 14706136
TI  - [Studies on the dynamics of biological characteristics of CD133+ cells from human
      umbilical cord blood during short-term culture].
AB  - This study was to investigate dynamics of biological properties of CD133(+) cells
      from human umbilical cord blood (UCB) during short-term culture containing the
      combination of hematopoietic growth factors and the feasibility of in vitro
      expansion of CD133(+) cells. The biology activities including analysis of cell
      cycle, immunophenotype, telomerase activity, expression of adhesion molecules and
      expansion potential of CD133(+) cells were monitored during ex-vivo expansion,
      and compared with those of CD34(+) cells. The results showed that the contents of
      CD133(+) and CD34(+) cells in fresh UCB were (1.05 +/- 0.73)% and (1.40 +/-
      0.56)% respectively. About 79.62% of CD34(+) cells expressed CD133, and more than
      97% of CD133(+) cells were CD133(+)CD34(+), markedly higher than that in CD34(+)
      fraction (P < 0.01). No significant differences were observed in content of cells
      expressing CD38, CD13, CD14, CD61 and glycophorin-A between the two fractions.
      Expansion of CD133(+), CD133(+)CD34(+) and CD34(+)CD38(-) cells at 10 days and
      those of CFU-mix, HPP-CFC and CD34(+)CD38(-) cells at 6 days from CD133(+) cells
      group were significantly higher than those from the CD34(+) cell group (P <
      0.05). Analysis of immunophenotype showed that CD133(+)CD34(+) cells declined
      gradually while CD133(-)CD34(+) and CD133(-)CD34(-) cells increased during ex
      vivo expansion; basal telomerase activities of fresh UCB CD133(+) and CD34(+)
      cells were low but significantly exceeded that of CD34(-) fraction (P < 0.05). At
      first week of expansion, telomerase activity was significantly upregulated, after
      two weeks, telomerase activity remarkably declined, and decreased to baseline or
      below the limits of detection in day 20. More than 90% of CD133(+) cells
      expressed CD49d and CD11a, and, more than 85% of the cells expressed CD54, about
      50% of cells expressed CD62L. At the early stage of expansion, expression of
      CD49d was upregulated, expression of CD11a remaining no change, while as
      expression of CD54 and CD62L was downregulated. Expression of all adhesion
      molecules was decreased gradually with extend of culture. But expression of these
      adhesion molecules on CD34(+) subsets were not affected significantly during
      expansion. It is concluded that CD133(+) population may be a more primitive
      hematopoietic stem/progenitor cells (HSPC) than CD34(+) cells, CD133(+) cells
      have great expansion potential for ex-vivo expansion and is a suitable target
      cell for ex-vivo expansion of HSPC. Downregulation of adhesion molecules and
      telomerase activity may be one of the reasons for delayed engraftment of expanded
      products.

PMID- 14706137
TI  - [Transduction efficiency of recombinant adeno-associated virus 2 in human
      umbilical cord blood CD34+ hematopoietic stem/progenitor cells].
AB  - To investigate the transduction efficiency of recombinant adeno-associated virus
      2 (rAAV-2) in human umbilical cord blood CD34(+) hematopoietic stem/progenitor
      cells, the CD34(+) cells sorted by the method of magnetic cell sorting from human
      cord blood were infected with the rAAV-2 expressing the green fluorescent protein
      (GFP) gene. After transduction for 19 hours, the expression of GFP was detected
      under fluorescence microscope. The results showed that 43% CD34(+) cells
      expressed the GFP gene at a multiplicity of infection of 2 x 10(5). It is
      concluded that the rAAV-2 can transduce human cord blood CD34(+) hematopoietic
      stem/progenitor cells efficiently.

PMID- 14706138
TI  - [Cloning of expression vector of human tissue factor gene and its expression in
      human ovarian cancer cell line].
AB  - The aim was to construct the expressive vector of human tissue factor (TF), and
      determine its expressive level in stable-transfected human ovarian cancer cell
      line. The human TFcDNA was obtained from human placenta by RT-PCR and then
      inserted into eukaryotic expressive vector pcDNA3 to obtain the TF-pcDNA3
      recombinant. This recombinant gene was introduced into human ovarian cell line
      A2780 through transfection mediated by lipofectamine. Stable-transfected cells
      were screened by G418. The TF expressive levels were detected by RT-PCR and flow
      cytometry. The results showed that: (1) the constructed product was identified as
      TF-pcDNA3 recombinant by sequencing. (2) TF was highly expressed not only at
      transcriptional level in the stable-transfected A2780 cell (transfected cell 3.99
      +/- 0.15, untransfected cell 0.97 +/- 0.23, P < 0.01), but also on the membrane
      of the cell surface [transfected cell (48.56 +/- 9.53)%, untransfected cell (2.73
      +/- 1.15)%, P < 0.01]. It was concluded that TF gene was successfully cloned, and
      was introduced into human ovarian cancer cell, and the subline A2780/TF which
      stably expresses TF at high level was obtained. It will provide good experimental
      basis for investigating new mechanisms of tumor growth, invasion, metastasis,
      hypercoagulability, and for exploring a new strategy of gene therapy.

PMID- 14706139
TI  - [Analysis of LRP15 Gene Expression Pattern and Its Expression in Leukemia Cells].
AB  - To explore the possible function of LRP15 gene in carcinogenesis and its
      significance in the classification and prognosis of leukemia, the expression
      pattern of LRP15 in normal tissues, tumor tissues and cell lines was detected
      with SAGE and gene expression database provided by NCBI and NCI respectively. RT
      PCR was used to detect the expression of LRP15 in leukemia patients. The results
      showed that LRP15 was expressed in different tissues and tumor cell lines, the
      positive rate of LRP15 in immature blood cells was higher than that of mature
      blood cells and the positive rate of M(1), M(2) and M(3) was higher than that of
      other AML subtypes (P < 0.01), the expression of LRP15 in refractory leukemia was
      higher than that of de novo leukemia. The results suggest that LRP15 may play an
      important role in carcinogenesis, AML classification and acute leukemia
      prognosis.

PMID- 14706140
TI  - [Improved RT-PCR for detection of PML/RARalpha fusion gene in rapid diagnosis of
      acute promyelocytic leukemia].
AB  - Detection of the PML/RARalpha fusion gene by RT-PCR in acute promyelocytic
      leukemia (APL) blasts is not only critical to commence promptly the specific
      therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (As(2)O(3)), but
      also essential for the definition of PML breakpoint type and subsequent
      monitoring of minimal residual disease (MRD). The current PML/RARalpha
      amplification techniques with conventional nested PCR are laborious and time
      consuming, which fails to meet the requirements for rapid diagnosis of APL in
      clinical practice. Therefore, an easily handled RT-PCR methodology for the rapid
      and accurate amplification of PML/RARalpha fusion transcripts is needed. A
      modified one round RT-PCR protocol was described with a few variations which
      includes rapid extraction of high quality cellular total RNA, cDNA synthesis with
      random hexamer and M-MLV reverse transcriptase, optimal concentrations of MgCl(2)
      (1 mmol/L), PCR primers (0.4 micro mol/L) and Taq polymerase (0.01 U/ micro l),
      hot-start procedure, and concomitant amplification of PML/RARalpha fusion gene
      and RARalpha internal control under the identical thermocycle parameters. The
      results in 40 patients with newly diagnosed APL showed that the improved RT-PCR
      protocol allowed the rapid detection of PML/RARalpha fusion gene and the accurate
      discrimination of its transcript types, and simultaneous amplification of
      RARalpha internal control under the identical program in less than 6 hours. There
      were no false positive or negative results found with the assay. In conclusion,
      the assay reported here is proved to be a simple, easily handled, and highly
      specific procedure for the diagnosis of APL cases, particularly those requiring
      such urgent therapeutic intervention as ATRA or As(2)O(3) and meriting its
      further application in APL management.

PMID- 14706141
TI  - [Establishment of urokinase receptor gene antisense RNA transfer system and its
      application in leukemia research].
AB  - Overexpression of urokinase-type plasminogen activator receptor (uPAR) on tumor
      cell surface is essential for invasion and metastasis in a variety of tumor
      cells. To establish a retroviral-mediated antisense RNA transfer system of uPAR
      gene for exploring its function on down-regulation of uPAR expression in leukemia
      cells, the retroviral vector LaCD87SN was constructed by inserting uPAR gene into
      LXSN vector in an antisense orientation. An uPAR gene antisense RNA transfer
      system was established by liposome-mediated transfection in combination with
      cross infection with retrovirus. Human leukemia cells U937 were transduced with
      aCD87 amphotropic retrovirus, expressing uPAR antisense RNA, and the U937/aCD87
      cells was obtained by G418 selection. The integration and expression of antisense
      uPAR gene were analyzed by polymerase chain reaction (PCR) assay. The cell
      surface expression of CD87 and the activities of matrix metalloproteinase (MMP)
      were assayed by flow cytometry (FCM) and gelatin zymography, respectively. The
      results showed that the amphotropic retroviral producers Am12/aCD87, which
      expressed antisense RNA of uPAR gene with a titer of 6.3 x 10(5) cfu/ml in
      supernatants, were obtained by means of transfection and superinfection.
      U937/aCD87 cells were established by continuative G418 selection after retrovirus
      infection. In U937/aCD87 cells, the integrated provirus and the overexpression of
      antisense uPAR gene was confirmed. Compared with U937/NeoR cells, FCM analysis
      revealed that CD87 expression on U937/aCD87 cell surface was not downregulated
      significantly. However, MMP-9 secretion was significantly suppressed in
      U937/aCD87 cells. In conclusion, although the retroviral-mediated antisense RNA
      transfer could not efficiently suppress uPAR expression on leukemic cell surface,
      it may interfere the uPAR-MMP interactions.

PMID- 14706142
TI  - [To inhibit ERK for enhancing chemotherapy sensitivity of drug-resistance cell
      lines of leukemia and ovarian carcinoma].
AB  - The aim was to study the roles of extracellular regulated protein kinases (ERK)
      and telomerase activity in drug resistance of human leukemia and ovarian
      carcinoma cells. Flow cytometry was used to analyze apoptosis rate. Telomere
      repeat amplification protocol (TRAP) and bioluminescence analysis method were
      used for detection of telomerase activity. The phosphorylated ERK(1/2) protein
      expression was observed by Western blot method. The results showed that the
      specific inhibitor PD98059 of ERK kinase 1 (MEK(1)) enhanced the sensitivity of
      HL-60/E6 leukemia cell lines to harringtonine (HRT) or COC1/DDP ovarian carcinoma
      cell lines to cis-dichlorodiamine platinum (DDP). Both PD98059 and chemotherapy
      drugs HRT and DDP reduced the phosphorylated ERK(1) and ERK(2) protein expression
      level, and down-regulated the telomerase activity. The sole action of each was
      inferior to the combination action of PD98059 and HRT or DDP. In conclusion, ERK
      and telomerase serve a function to some extent in drug resistance of leukemia and
      ovarian carcinoma cells. The inhibition of ERK signal transduction pathways led
      to reduction of phosphorylated ERK(1) and ERK(2) protein expression level, and
      successionally down-regulated the telomerase activity. The final result was to
      enhance the sensitivity of HL-60/E6 to HRT or COC1/DDP to DDP.

PMID- 14706143
TI  - [The reverse effect on drug-resistance against tyrosine kinase inhibitor STI571
      in mdr1 and bcr-abl positive leukemic cells].
AB  - To explore the possibility of leukemia cell line of both bcr-abl and mdr-1
      positive were cross-resistant to tyrosine kinase inhibitor STI571 and its
      reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected
      with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with
      IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing
      bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18,
      1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It
      could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha.
      In conclusion, amplification of mdr1 gene may contribute to drug-resistance of
      bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and
      IFN-alpha show obviously reverse effects on drug-resistance. The combination of
      half-dose of both CsA and IFN-alpha display stronger effect than the full dose of
      either.

PMID- 14706144
TI  - [Reversal effect of berbamine on multidrug resistance of K562/A02 cells and its
      mechanism].
AB  - This preject is to explore the reversal efficacy of calmodulin antagonist
      berbamine (BBM) on multidrug resistance (MDR) and its mechanism. Human
      erythroleukemic cell line K562 and its adriamycin-resistant counterpart K562/A02
      were used in the study. The cells were co-cultured with ADR and BBM in different
      concentrations. MTT assay was used to analyze the effect of BBM on cell growth
      inhibition. According to the MTT assay, the 50% inhibitory concentration
      (IC(50)), the multiples of drug resistance and increased sensitivity of ADR were
      calculated. The concentration of intracellular ADR and expression level of P-gp
      were detected by flow cytometry (FCM). The expression level of mdr1 mRNA and
      survivin mRNA was detected by semi-quantitative reverse transcriptase polymerase
      chain reaction (RT-PCR) with beta-actin as internal reference. The results showed
      that IC(50) of ADR in K562 and K562/A02 cells was 1.16 +/- 0.09 micro mol/L and
      37.47 +/- 1.76 micro mol/L, respectively. The resistant multiple of K562/A02
      cells to ADR was 32.30 higher than that of K562 cells. BBM increased the chemo
      sensitivity of ADR in K562/A02 cells with dose-dependent relationship, i.e. when
      5, 10 and 20 micro mol/L BBM was added in the culture the chemo-sensitivity of
      ADR was increased to 2.01-, 9.68-, and 41.18-fold (P < 0.01), respectively. After
      treating K562/A02 cells by 5 or 10 micro mol/L BBM for 2 hours the accumulation
      of intracellular ADR was increased to 1.41- and 1.52-fold (P < 0.01),
      respectively. Treating by BBM for 72 hours decreased 4.12% (P < 0.05) and 27.09%
      (P < 0.01) of P-gp expression, respectively, meanwhile down-regulated expression
      of mdr1 mRNA and survivin mRNA was found. In conclusion, BBM could increase
      intracellular concentration of ADR in K562/A02 that down-regulated expression
      level of mdr1 mRNA and P-gp and survivin so that the sensitivity of K562/A02 to
      ADR was increased significantly.

PMID- 14706145
TI  - [The experimental study on idiotypic DNA vaccine against human B-cell lymphoma to
      induce antitumor immune response].
AB  - The purpose of this study was to evaluate whether the DNA vaccine containing
      idiotypic gene fragment of human B-cell lymphoma cell line Namalwa could elicit
      the specific anti-idiotypic immune response in vivo. The candidate gene fragment
      of the lymphoma cell, variable region of heavy chain (VH) of the membranous
      immunoglobulin, was amplified using Ig superfamily primers by means of RT-PCR.
      Also, the intact cDNA of murine monocyte chemoattractant protein (MCP-3) was
      cloned and used as the adjuvant molecular. The two gene fragments of VH and MCP-3
      were fused together by 8aa linker peptide with recombinant PCR. Subsequently, the
      fusion gene fragment was cloned into eukaryonic expression vector pcDNA3.1 to
      construct DNA vaccine plasmid. Prior to the immunization, the transient
      transfection coupled with RT-PCR was performed to prove that the recombinant
      plasmid could express in eukaryonic cells in right way. Then two groups of mice
      were immunized by intramuscular injection with DNA vaccine and mock plasmid
      pcDNA3.1 respectively. Three times of injection were performed with 100 micro g
      plasmid respectively at the beginning of the experiment and 2, 4 weeks after the
      first injection for all the groups. FACS analysis was chosen to detect the
      antibodies recognizing lymphoma cells at different time following vaccination.
      The results demonstrated that specific anti-idiotypic antibody could be detected
      in the group of DNA vaccine immunized mice as early as eight weeks after the
      first immunization. Further test demonstrated that the anti-idiotypic antibody
      could maintain for at least twenty weeks with high titer. Anti-idiotypic
      antibodies were elicited in three of five mice of the DNA vaccine immunized
      group. The Abs of DNA vaccine immunized mice could only recognize Namalwa cell
      line instead of another unrelated human cell line A549. There is no cellular
      response detected in the DNA vaccine immunized mice. It is concluded that the DNA
      vaccine containing fused MCP3-VH sequence could elicit specific anti-idiotypic
      antibody against B-cell lymphoma in vivo and could be used in further study of
      DNA vaccine against B-cell lymphoma. The results would provide the basis for
      further studies and optimization of this therapeutic strategy on patients with B
      lymphoproliferative disease.

PMID- 14706146
TI  - [Study on blocking the tumor immune escape by Fas ligand pathway].
AB  - The expression of Fas ligand (FasL) on the membrane of many kinds of leukemia or
      solid tumor cells played an important role in the immune escape of tumor cells.
      This study was aimed to know if the soluble Fas (sFas), expressed by adenovirus,
      could block the immune escape of tumor cells by FasL pathway. The two recombinant
      adenoviral vectors, AdsFas with murine soluble Fas gene and AdEGFP with enhanced
      GFP protein gene, were constructed by homologous recombination between two
      plasmids in Escherichia coli with the AdEasy adenovirus vector system. The
      viruses were propagated and purified by two times ultracentrifugation. Their
      titres were detected by plaque assays. The expressed protein was evaluated by
      Western blot analysis. Then the tumor EL4 cells were infected with AdsFas and
      AdEGFP respectively. The apoptosis ratio of the target cells-YAC-1 cells induced
      by EL4 cells was respectively detected by (3)H-thymidine ((3)H-TdR) labeling. The
      results showed that the recombinant adenoviral vectors AdsFas and AdEGFP were
      successfully obtained. The titres of viruses purified by two times
      ultracentrifugation were up to 10(11) pfu/ml by plaque assays. The sFas protein
      was highly expressed in the target cells by Western blot analysis. After the EL4
      cells were transfected with the adenoviruses AdsFas, the apoptosis rate of YAC-1
      cells in the sFas transfection group (respectively 6%, 7% and 9% when the
      effector:target (E:T) was 3:1, 10:1 and 30:1) was obviously lower than that in
      the control group (respectively 28%, 37% and 45%), P < 0.01. But when the EL4
      cells were transfected with AdEGFP, the apoptosis rate of YAC-1 cells
      (respectively 30%, 36% and 48%) was similar to the control group, P > 0.05. In
      conclusion, the transfer of sFas by adenovirus could inhibit the apoptosis of
      Fas(+) cells-YAC-1 cells induced by tumor EL4 cells. It showed that the
      transduction of sFas could block the effect of the immune escape of EL4 cells
      through FasL in vitro. These results thus provide a new direction to find a way
      to treat tumors.

PMID- 14706147
TI  - [Camouflage of HLA-I antigen in lymphocyte surface].
AB  - The objective of this study was to investigate the method and effect of blocking
      the specific reaction between lymphocyte HLA-I antigen and its antibody. The
      lymphocytes were disposed with 12 mmol/L methoxypolyethelene glycol benzotriazol
      carbonate (mPEG-BTC) in concentration gradient in PBS (pH 7.4) at 22 degrees C.
      The effect of the modified lymphocytes was detected by microlymphocytotoxicity
      assay. The results showed that lymphocytes modified by mPEG-BTC did not react
      with related HLA-I antibodies in microcytotoxicity test. It is suggested that the
      specific reaction between HLA-I antigen of lymphocyte and HLA-I antibodies can be
      completely camouflaged by mPEG-BTC in PBS (pH 7.4) under 22 degrees C room
      temperature.

PMID- 14706148
TI  - Expression of killer cell inhibitor receptors on immunocompetent cells with
      relation to graft-versus-host disease after hematopoietic stem cell
      transplantation.
AB  - The study was aimed at the exploration of relationship between T cells expressing
      killer cell inhibitor receptors (KIR, CD158 and CD94) and graft-versus-host
      disease (GVHD) after hematopoietic stem cell transplantation. The expression
      rates of CD158a, CD158b and CD94 on T cells and NK cell were detected by flow
      cytometry and donor/recipient HLA-Cw was analyzed using PCR after peripheral
      blood stem cell transplantation (PBSCT) and umbilical cord blood transplantation
      (UCBT). After both PBSCT and UCBT, the rates of CD3(+)CD158a(+) and
      CD3(+)CD158b(+) T cells increased, especially the rate of CD8(+)CD158b(+) T
      cells. In both acute and chronic GVHD groups, the rate of CD3(+)CD158b(+) T cells
      increased, especially in acute GVHD. The CD94 mainly expressed on CD3(+)CD8(+) T
      cells. The percentage of the expression of CD94 on CD4(+) and CD8(+) cells after
      UCBT and PBSCT increased significantly. The expression of KIR in GVHD (early
      stage of transplantation) increased but the expression of KIR in chronic GVHD
      (advanced stage of transplantation) decreased. Five patients who HLA-Cw matched
      had no severe GVHD. In four patients who underwent allo-PBSCT and UCBT from
      related HLA-matched donors, only 2 patients had no aGVHD. Four patients underwent
      transplantation from unrelated HLA-matched donors had GVHD. These observations
      suggested that there is some relationship between GVHD and KIR expression on T
      cells. CD158b might be an inhibitory molecule of T cell activated at early stage
      after transplantation. Understanding the mechanism of GVHD with the expression of
      KIR on T cells, especially those binding the HLA-Cw might shed light on the
      establishment of the specific immunotolerance for the prevention of GVHD. To pay
      attention to HLA-Cw typing is very important to reduce GVHD and increase GVL
      effect in related or unrelated HLA-matched transplantation.

PMID- 14706149
TI  - [The improving effect of bone marrow stromal cell transfected with IL-3 gene on
      hematopoietic reconstitution in bone marrow transplantation of mice].
AB  - To study the improving effect of regulatable gene of IL-3 engineered bone marrow
      stromal cell on the hematopoietic reconstitution in allogeneic bone marrow
      transplantation, an inducible gene expression system was established in a bone
      marrow stromal cell line which expressed IL-3 gene induced by doxycycline (Dox).
      The lethally irradiated mice C57BL/6 (H-2(d)) were co-transplanted with
      allogeneic bone marrow (BALB/c, H-2(d), 1 x 10(7)/mice) in which T cell were
      depleted by monoclonal antibody anti-Thy1.2 added with complement and the gene
      engineered stromal cell QXMSC1tet-on + IL-3 (5 x 10(5)/mice) at the same time.
      Dox was administrated continuously for 15 days to induce the expression of IL-3.
      The hematopoiesis in the bone marrow transplanted mice were observed at 30, 60
      days post-transplantation, respectively. The numbers of RBC and WBC in peripheral
      blood were counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were
      measured in recipient bone marrow. The results showed that the engineered stromal
      cell line achieved high-level and controllable IL-3 expression. Co-graft with
      QXMSC1tet-on + IL-3 significantly increased the number of RBC, WBC in recipient
      peripheral blood, and the nucleated cells, CFU-S, CFU-GM, CFU-E, CFU-GEMM in bone
      marrow, compared with those coinfused with QXMSC1 or QXMSC1tet-on-TRE as control.
      In conclusion, regulatable gene IL-3 engineered bone marrow stromal cells
      accelerates hematopoietic reconstitution after allogeneic bone marrow
      transplantation.

PMID- 14706150
TI  - [The effect of granulocyte colony stimulating factor on T-cell subsets in
      peripheral blood and its correlation with the mobilization effect of CD34+
      cells].
AB  - The objective was to observe the effect of G-CSF as a mobilizer of hematopoitic
      stem cells on the absolute counts of T-cell subsets in peripheral blood and their
      relevance with the mobilized CD34(+) cells. The examples of peripheral blood from
      26 patients performed of autologous stem cell transplantation were taken before
      and after mobilization by G-CSF. Flow cytometry was used for detecting CD3(+),
      CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD4(+)CD8(+) and CD3(+)CD4(-)CD8(-) cells.
      Concurrently, their correlations with mobilized CD34(+) cells in peripheral blood
      were compared. The results showed that after the mobilization by G-CSF, the
      amounts of CD3(+), CD3(+)CD4(+), CD3(+)CD4(+)CD8(+) and CD3(+)CD4(-)CD8(-) cells
      in peripheral blood increased by 2.23, 2.62, 2.99 and 10.96 fold respectively,
      but that of CD3(+)CD4(-)CD8(+) cells was nearly no changed (P = 0.243). The
      correlation coefficient of CD3(+)CD4(-)CD8(-) cells and mobilized CD34(+) cells
      was 0.796, (P = 0.000) and no correlation with other T-cell subsets. It was
      concluded that when CD34(+) cells were mobilized by G-CSF from bone marrow to
      peripheral blood, the absolute counts of the peripheral T-cell subsets got
      changed. The increase of CD3(+)CD4(-)CD8(-) cells had correlated with
      mobilization effect of CD34(+) cells into peripheral blood.

PMID- 14706151
TI  - [Observation on gene polymorphism of Rh blood group in Chinese Han nationality].
AB  - To observe the gene polymorphism of Rh blood group in unrelated random
      individuals and families for Chinese Han nationality, polymerase chain reaction
      sequence specific primer (PCR-SSP) was used to amplify the Rh C/E gene, RhD gene,
      exons, intron 2 and 10, insert and Rh Box in 160 blood samples of RhD positive
      unrelated individuals and 71 samples of RhD negative unrelated individuals and 7
      samples of families whose probands were RhD-negative. The results showed that RhD
      genes of RhD-negative individuals with C antigens were polymorphism, three forms
      were found for D exon including intact, partial deletion and complete deletion
      exons. Insert fragments and Rh Box were found in most cases of families whose
      probands were RhD-negative and its inheritance accorded with the Mendel's Law,
      and it did not affect the expression of RhD gene. "Normal" RhD exon 4 amplifying
      product was not found in all of the samples. It was concluded that gene structure
      of the RhD-negative in Chinese was polymorphism, intact, partial deletion and
      complete deletion exons were found in the individuals with C antigen and probably
      existed specific D (nf) Ce haplotype. The function of insert was uncertain. The
      Rh gene sequences of Chinese Han nationality are different from those of
      Caucasian and the Rh gene library based on Han nationality should be established.

PMID- 14706152
TI  - [The effect of antioxidant on optimation of blood preservation].
AB  - In order to optimize the preservation of blood, 3 kinds of antioxidant were
      selected and each of them can be injected directly into vein, then the optimal
      dose of these antioxidants was chosen using statistical method; ISMC (injectio
      salvia miltiorrhizae composita), ginaton and the combination of ISMC and ginaton
      were added into blood as optimal dose, some references as ATP, EI and so on were
      observed during blood preservation. The results showed that all of the three
      kinds of antioxidants increased ATP, EI and decreased FHb during blood
      preservation. It is concluded that both of ISMC and ginaton can effectively
      optimize the preservation of blood and combination of ISMC and ginaton can
      produce additive effect.

PMID- 14706153
TI  - [Effects of leukocyte elimination before storage on quality of red blood cell
      concentration].
AB  - The objective of this study was to explore the possible effects of leukocyte
      elimination by filteration before storage on the quality of red blood cell
      concentrations (RCC) that prepared through two procedures. Eight units of red
      blood cell concentrations derived from whole blood after plasma separated (RCC1)
      and eight units of red blood cell concentrations derived from whole blood after
      platelet-rich plasma separated (RCC2) were divided randomly into filtered group
      and control group respectively. The RCC of filtered group were filtered by
      leukocyte deplete filter before storage. The control group didn't have any other
      treatments. These two groups were stored for five weeks at 4 degrees C according
      to AABB standard. Mean corpuscular volume (MCV), mean corpuscular hemoglobin
      (MCH), mean corpuscular hemoglobin concentration (MCHC) and plasma concentration
      of K(+) and lactate dehydrogenase (LDH), free hemoglobin (FHb), adenosine
      triphosphate (ATP) of red blood cell of all RCC were evaluated weekly, and
      bacteria contamination of all RCC was also detected after five weeks of storage.
      The results showed that there was no difference of MCV, MCH and MCHC and ATP
      level of red blood cell in all RCC of two groups, the ATP of red blood cell was
      lower than the control group on week 4 and 5. The average concentration of K(+)
      of the filtered group was less than the control group. The differences are
      significant except that of RCC1 stored till the third week. The plasma LDH
      concentration of filtered group was less than the control group, and the
      differences were exacerbate during the storing time prolonged. FHb release in the
      filtered group of RCC2 was significant less than that of control, but no
      significant difference was found between the two groups of RCC1. It was concluded
      that leukocyte elimination by filter before storage could be benefit to RCC
      preservation.

PMID- 14706154
TI  - [Preliminary study on conversion of RhD positive red blood cells to RhD negative
      by modification with methoxy polyethylene glycol].
AB  - Rh is a very important blood group like ABO blood system in transfusion medicine.
      It causes severe transfusion reaction and hemolytic disease of the newborn (HDN)
      if RhD blood group does not match between the donor and the recipient. The
      population of RhD negative is only about 0.2% - 0.5% in Chinese. Conversion of
      RhD positive RBCs to RhD negative is very important in clinical transfusion. This
      study was to try to modify RhD antigen located on the surface of A, B, O and AB
      red blood cells in order to convert RhD positive to RhD negative by the
      modification of four kinds of methoxypolyethylene glycol (mPEG) derivatives and
      to observe the effect of mPEG modification on cell morphology, structure and
      function. The result demonstrated that modification efficiency of mPEG-BTC (mPEG
      benzotriazole carbonate) was better than other three kinds of mPEG derivatives.
      It could camouflage RhD antigen efficiently when the concentration reached to 1
      mmol/L. The result also showed that there were no harmful effects of mPEG
      modification on cell morphology, osmotic fragility, hemolysis, AchE, cholesterol,
      ATP, 2,3-DPG and deformability. It is suggested that success in converting RhD
      positive RBCs to RhD negative was preliminarily achieved.

PMID- 14706155
TI  - [Change of expression of cell adhesion molecules CD11a and CD49d in patients with
      chronic aplastic anemia before and after therapy].
AB  - To explore the cell adhesion molecules (CAMs) CD11a and CD49d in patients with
      chronic aplastic anemia (CAA) and its clinical implications, the expression of
      CD11a and CD49d in mononuclear cell (MNC) of bone marrow (BM) and peripheral
      blood (PB) were measured using APAAP techniques in 20 patients with CAA before
      and after SSL/C therapy. The results showed that the expression of CD11a and
      CD49d in MNC of BM and CD11a in MNC of PB increased significantly (P < 0.05)
      after SSL/C therapy, and there was no significant change of CD49d in MNC of PB in
      both groups. In conclusion, the decrease of CAMs of CD11a and CD49d participated
      in the pathogenesis of CAA. The expression of CAMs increases with effective
      treatment, so the restoration or improvement of altered CAMs of CAA might be
      beneficial to the proliferation and differentiation of hematopoietic stem cell,
      and improvement of hematopoiesis in CAA.

PMID- 14706157
TI  - [Hairy cell leukemia: report on one case with survival for 10 years].
AB  - One case of hairy cell leukemia with survival for 10 years was reported. The
      patient received Interferon-alpha(2b) treatment continuously for more than 9
      years and intravenous administration of fludarabine for 2 courses of treatment in
      the later period, and died due to complication of severer infection in thd end.
      The manifestation, diagnosis and treatment of hairy cell leukemia were discussed.

PMID- 14706156
TI  - [Interleukin-18 and its related cytokines in plasma of patients with idiopathic
      thrombocytopenic purpura].
AB  - To explore the role of immune regulating cytokines in pathogenesis of the
      idiopathic thrombocytopenic purpura (ITP) and its clinical significance, the
      levels of IL-18, TNF-alpha and Sc5b-9 in plasma of 32 ITP patients and 18 normal
      individuals were detected using ELISA methods. The results showed that IL-18, TNF
      alpha and sC5b-9 levels in plasma of ITP patients were higher than that in normal
      individuals. The level of IL-18 was positively correlated with the levels of TNF
      alpha and sC5b-9. In conclusion, The rising levels of the IL-18, TNF-alpha and
      sC5b-9 were correlated with disorder of Th1/Th2 subsets, and may contribute to
      the immune dysfunction in ITP patients. The dynamic observation of these
      cytokines may be useful in directing the clinical treatment for ITP patients.

PMID- 14706158
TI  - [Estimate of Recent Thymic Output Function - Quantification of T Cell Receptor
      Rearrangement Excision Circles (TRECs)].
AB  - For a long time, thymic function could not be monitored, as a consequence of the
      absence of adequate technology to detect recent thymic emigrants from naive T
      cells. T cell differentiation in the thymus is characterized by T cell receptor
      (TCR) rearrangement. During the rearrangement of TCRalpha gene segments, the
      deltaRec and psiJalpha rearrange to each other to delete the TCRdelta gene and
      form an extrachromosomal DNA circles, referred to as signal joint T cell receptor
      excision DNA circles (sjTRECs) or TRECs. TRECs are assumed to have a high
      stability, they can not multiply and consequently are diluted during T cell
      proliferation. It was recently suggested that quantitative detection of TRECs
      would allow for direct measurement of thymic output. In this review TRECs
      quantification is a powerful method to evaluate the thymic output function in
      both health and disease, including hematopoietic stem cell transplantation,
      hematopoietic malignancies, HIV infection and autoimmune disease, and so on is
      described.

PMID- 14706159
TI  - [The research update on cellular immune abnormality in myelodysplastic syndrome-
      review].
AB  - Myelodysplastic syndrome is a group of diseases characterized by abnormal clonal
      proliferation of hematopoietic cells and pancytopenia with dysplasia. The
      pathogenesis of MDS includes factors of chromosome aberrations, gene mutations,
      immune abnormalities, environmental changes, and so on. Now it is commonly
      accepted that MDS is a multistep process disorder involving more etiologic
      alterations. Recently more and more investigations indicate that the abnormality
      of cellular immunity is one of important reasons related to MDS. Some proofs
      about the abnormal activation of T-cell and the abnormal expressions of cytokines
      in different stages of immune response in MDS have been documented, meanwhile,
      numerous clinical studies on immune therapy in MDS provide a great number of
      evidences to disclose its immune abnormalities.

PMID- 14706161
TI  - Creating a molecular classification for lung cancer.

PMID- 14706160
TI  - [Application of cyclosporine A in myelodysplastic syndrome--review].
AB  - Treatment of myelodysplastic syndrome (MDS) remains unsatisfactory. It is
      possible that immunosuppressive therapy might be effective for a certain subset
      of patients with MDS. In this review 105 patients with MDS who were treated with
      cyclosporin A (CsA) including 90 RA, 5 RARS, 10 RAEB, were analyzed. The dose of
      CsA was 2 - 12 mg/(kg x d) for at least three months. Hematological improvement
      was observed in 64 patients (61%), and complete remission was observed in 14
      patients (13.3%). These results indicated that CsA immunosuppressive therapy may
      be useful for IPSS low, intermediate-1 and intermediate-2 MDS patients.

PMID- 14706163
TI  - Novel drugs in development for malignant mesothelioma.

PMID- 14706164
TI  - The validity and clinical utility of symptom monitoring in advanced lung cancer:
      a literature review.
AB  - Symptom monitoring and quality-of-life (QOL) evaluation in lung cancer patients
      might improve care. Brief, valid, and responsive tools are available to measure
      symptoms and their effect on QOL. Instruments available for use in lung cancer
      patients can be classified into 3 categories: generic, cancer-specific, and lung
      cancer symptom-specific. These instruments might assist clinicians in assessing
      and interpreting treatment outcomes from the patient perspective. They also can
      assist in treatment decision making, symptom palliation, and they might even be
      prognostic of survival. Over the past 20 years, these brief evaluations have been
      used in clinical trials to evaluate patient-reported outcomes. Now, with the
      advent of less toxic, targeted molecular therapies such as gefitinib (Iressa) in
      non-small-cell lung cancer, these instruments' value in showing symptomatic
      improvement from tumor control or regression might be further enhanced. To date,
      however, such assessments are not widely implemented in routine clinical
      practice. To better understand benefits of such assessments, we review existing
      evidence surrounding the instruments' use, evaluate their success, and highlight
      recent developments. We hope to encourage clinicians to incorporate these
      evaluations in clinical practice.

PMID- 14706165
TI  - Adjuvant therapy in the treatment of non-small-cell lung cancer.
AB  - Randomized trials to date have not consistently demonstrated a benefit in overall
      survival with the use of adjuvant chemotherapy, radiotherapy, or combined
      modality chemoradiation in patients with resected non-small-cell lung cancer.
      Subset analyses suggest a reduction in local relapse with adjuvant radiotherapy
      for patients with completely resected N2 disease. Improvements in patient
      selection and treatment plans are urgently needed.

PMID- 14706166
TI  - Phase II study of docetaxel/vinorelbine in patients with non-small-cell-lung
      cancer previously treated with platinum-based chemotherapy.
AB  - The aim of this phase II trial was to assess the efficacy and tolerability of
      docetaxel/vinorelbine as second-line therapy. Thirty-two patients with a
      performance status (PS) of <or= 2 (5 with locally advanced and 27 with metastatic
      non-small-cell lung cancer [NSCLC]) who were previously treated with platinum
      based chemotherapy, were recruited. Docetaxel 75 mg/m2 on day 1 and vinorelbine
      20 mg/m2 on days 1 and 5 were administered every 3 weeks with dexamethasone
      premedication but without prophylactic granulocyte colony-stimulating factor and
      antibiotics. The overall response rate (intent-to-treat analysis) was 9.5%,
      including 3 patients with a partial response, 15 (47%) with stable disease, and 9
      (28%) with progressive disease. Myelosupression was the limiting toxicity, with 8
      episodes of febrile neutropenia and 3 deaths due to sepsis. Median overall
      survival and progression-free survival were 25 weeks and 13 weeks, respectively.
      Patients with a PS of 2 (P < 0.02) and elevated lactate dehydrogenase (P < 0.01)
      had a worse prognosis. Histology of adenocarcinoma appeared to positively
      influence survival (P = 0.09). Our study confirms that the docetaxel/vinorelbine
      schedule has activity in NSCLC patients pretreated with platinum-based therapies.

PMID- 14706167
TI  - The role of apoptosis-related genes in non-small-cell lung cancer.
AB  - Both intrinsic and acquired resistance to chemotherapeutic drugs are major
      obstacles in the treatment of non-small-cell lung cancer. Apart from classical
      drug resistance mechanisms, the failure of tumor cells to undergo apoptosis also
      plays an important role in drug resistance. Mutations and defects in the
      apoptotic pathway are, therefore, additional factors that determine drug
      resistance. The tumor suppressor gene p53, the retinoblastoma gene, and the bcl-2
      family members are important factors in this pathway. Recently much attention has
      been drawn to different apoptotic pathways induced by naturally occurring death
      receptor ligands (such as tumor necrosis factor, Fas ligand, and tumor necrosis
      factor-related apoptosis-inducing ligand) or induced by drugs that affect the
      downstream pathway from the epidermal growth factor receptor. Insight regarding
      the proteins that determine sensitivity for chemotherapeutic drugs could provide
      new targets for cancer treatment, which may help to at least partly overcome drug
      resistance in non-small-cell lung cancer

PMID- 14706168
TI  - Adrenal hemorrhage secondary to metastasis from lung cancer.
AB  - The adrenals are common metastatic sites for lung cancers as well as a number of
      other primary cancers. Usually these metastases are asymptomatic. Hemorrhagic
      adrenal metastases from lung cancer are extremely rare. Only 5 prior reports of
      hemorrhagic adrenal metastases from lung cancer have appeared in the English
      literature. We report a case of spontaneous, massive, adrenal hemorrhage
      secondary to metastatic lung cancer in a 62-year-old patient. In lung cancer,
      patients with sudden onset of pain in the flank or back in association with
      anemia and hypotension, adrenal hemorrhage secondary to metastatic disease should
      be considered in the differential diagnosis. Computed tomography scans and
      magnetic resonance imaging aid in confirming the diagnosis.

PMID- 14706169
TI  - Phase I study of sequential deoxyazacytidine/depsipeptide infusion in patients
      with malignancies involving lungs or pleura.

PMID- 14706171
TI  - Highlights from: XII European Cancer Conference, Copenhagen, Denmark, September
      21-25, 2003.

PMID- 14706172
TI  - Current studies with PTK787, an oral inhibitor of vascular endothelial growth
      factor in colorectal cancer.

PMID- 14706173
TI  - Integrating oxaliplatin and capecitabine in adjuvant therapy of high-risk
      colorectal cancer.

PMID- 14706174
TI  - Development of new agents for the treatment of advanced colorectal cancer.
AB  - During the past decade, there have been several significant advances in the
      treatment of metastatic colorectal cancer. These include the introduction of the
      cytotoxic agents capecitabine, irinotecan, and oxaliplatin. Given their diverse
      mechanisms of action and toxicity profiles, combinations of fluoropyrimidines,
      irinotecan, and oxaliplatin have proven feasible and have improved patient
      outcomes compared with 5-fluorouracil alone. Recently, improved understanding of
      the biology of colorectal cancer has led to the identification of new molecular
      targets and the development of pharmacologic agents that hold promise for greater
      tumor selectivity than traditional cytotoxic agents. Two approaches with early
      indications of clinical activity against colorectal cancer are inhibition of
      epidermal growth factor receptor signaling and inhibition of the vascular
      endothelial growth factor pathway. Furthermore, biochemical and genetic profiling
      of individual tumors, as well as patient genotyping, may ultimately guide
      clinicians in making rational treatment decisions based on predicted antitumor
      efficacy or toxicity of selected agents. This article reviews these recent
      advances in the systemic treatment of colorectal cancer, including discussion of
      promising agents in clinical development.

PMID- 14706175
TI  - Systematic review of management of colorectal cancer in elderly patients.
AB  - This study is designed to clarify the benefits and risks of chemotherapy and
      radiation therapy in elderly patients with colorectal cancer through a systematic
      review of the literature. Searches of the Medline, Embase, and Cochrane Library
      databases; PDQ  Cancer Information Summaries, American Society of Clinical
      Oncology Guidelines, Cancer Care Ontario Practice Guideline Initiative,
      Interprovincial Drug Strategies and Guidelines Group, and OncoLink Web sites; and
      manual searches of meeting proceedings and bibliographies were performed.
      Additional studies known to the authors were also identified. Randomized
      controlled trials, reviews, and guidelines evaluating the impact of age on
      overall survival and/or toxicity with adjuvant and palliative therapies for
      colorectal adenocarcinoma were selected. A preset study selection form was
      applied to all identified studies. All selected studies underwent a preset study
      appraisal. Analyses of the effect of age on overall survival benefits and/or
      toxicity of therapy were extracted. A qualitative synthesis and narrative review
      was undertaken. There is good evidence to support that patients = 80 years of age
      have similar overall survival benefits with adjuvant 5-fluorouracil (5-FU)-based
      chemotherapy for colon cancer and with palliative first-line monotherapy for
      metastatic colorectal cancer, as do younger patients. Data are limited with
      regard to toxicity of therapy in older patients in these settings. An increase in
      toxicity with bolus 5-FU chemotherapy regimens is evident. There is a paucity of
      data regarding adjuvant treatment of older patients with rectal cancer. More
      elderly patients need to be enrolled in clinical trials in order to fully
      evaluate the outcomes of colorectal cancer therapy in this population. Further
      studies are warranted.

PMID- 14706176
TI  - Management and outcome of colorectal cancer in elderly patients.

PMID- 14706177
TI  - A multicenter phase II study of irinotecan in patients with advanced colorectal
      cancer previously treated with 5-fluorouracil.
AB  - This multicenter, open-label, phase II study was performed to assess the efficacy
      and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with
      advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU).
      The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient)
      were administered. The overall objective response rate on an intent-to-treat
      basis was 18% (with 1 complete response and 20 partial responses), whereas 42
      patients (37%) showed stable disease. Median time to progression was 4.8 months
      and median survival was 13.6 months. Grade 3/4 toxicities included delayed
      diarrhea (19.1%), nausea/vomiting (10.4%), and neutropenia (8.7%). There were 2
      toxic deaths, 1 from delayed diarrhea and 1 from hemorrhage and grade 4
      mucositis. In conclusion, the present study confirms the antitumor efficacy of
      irinotecan monotherapy in patients with CRC pretreated with 5-FU.

PMID- 14706178
TI  - Gene mutations in advanced colonic polyps: potential marker selection for stool
      based mutated human DNA assays for colon cancer screening.
AB  - The detection and removal of advanced colonic polyps (ACPs) can help prevent the
      development of colorectal cancer. A set of DNA mutations known to be associated
      with colorectal carcinoma was tested against resected ACPs to determine the set s
      potential utility as a marker panel for ACPs. A sensitive mutation marker panel
      could be used by stool-based assays that look for mutated human DNA to detect the
      presence of ACPs. DNA from 32 ACPs = 1.0 cm in diameter was amplified and tested
      for 19 colorectal cancer associated DNA mutations and for deletions in BAT-26
      (microsatellite instability). One or more mutations were identified by
      microsequencing in 28 of the 32 ACPs (88%). Mutations were identified in k-ras
      (59%), APC (33%), and p53 (22%). BAT-26 mutation, a marker for microsatellite
      instability, was not identified. Stool DNA based assays that can identify these
      mutations may significantly increase the identification of patients with
      potentially premalignant ACPs for evaluation and treatment by colonoscopy.

PMID- 14706179
TI  - Randomized trial comparing the addition of oxaliplatin or irinotecan to high-dose
      leucovorin and 5-Fluorouracil intravenous bolus every two weeks in metastatic
      colorectal carcinoma: Southern Italy Cooperative Oncology Group 0103.

PMID- 14706191
TI  - [Impact of secondary pancreatic infection on the prognosis of patients with
      severe acute pancreatitis: an analysis of 60 cases].
AB  - OBJECTIVE: To investigate the impact of secondary pancreatic infection (SPI) on
      the prognosis of patients with severe acute pancreatitis (SAP). METHODS: Clinical
      data of 60 patients with SAP (January 1, 1980-December 31, 1999), especially the
      data at the onset of SPI, were retrospectively analyzed. RESULTS: Sixty patients
      were divided into two groups: SPI group (29 cases) and non-SPI group (31 cases).
      There was no significant difference in gender, average age, scores of Ranson and
      of high risk factors of China Medical Association between two groups, but the
      average stay days in hospital, payment, acute physiology and chronic health
      evaluation II (APACHE II) scores, days of fever, prehospital days, days of high
      white blood cell (WBC) count, the duration of constipation after the onset of SAP
      and average times of operation were significantly higher in SPI group than that
      of non-SPI group. Fatality rate of SPI group (7/29, 24.14 percent) was higher
      than that of non-SPI (1/31, 3.23 percent). There were 14 cases of infection with
      single microorganism (48.3 percent) and 15 cases of mixed infection (51.7
      percent) in SPI group. Twenty-seven patients were infected with bacteria of
      Enterobacteriaecae (Escherichia 25, Klebsiella pneumoniae 1, Proteus morgani 1, 8
      with bacteria of Pseudomonas (P. aeruginosa 7, P. stanieri 1), 2 with fungus, 5
      with other bacteria (Bacillus subtilis 2, Tetracoccus 1, Acetobacteraceae 1,
      Staphylococcus epidermidis 1) in SPI group. Only in 2 patients with infective
      pancreatic necrosis the blood culture was positive (Escherichia coli).
      CONCLUSION: These results showed that the major source of SPI is entergenous, and
      SPI would affect the prognosis of SAP patients. With the present therapeutic
      regimes it was hard to prevent entergenous infections. It is necessary to find a
      new strategy.

PMID- 14706192
TI  - [Effects evaluation of middle mode artificial liver in treatment of severe
      hepatitis].
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of middle mode artificial
      liver-plasma pheresis in treatment of severe hepatitis. METHODS: Seventeen
      patients with severe hepatitis were treated with plasma pheresis. The results of
      liver function, renal function, blood routine, prothrombin time (PT), prothrombin
      time activity (PTa) before and after the treatment were analyzed. All patients
      were observed closely. RESULTS: Symptoms of patients treated with plasma pheresis
      were improved, and the total effective rate reached 58.8 percent, but the
      survival rate was only 11.8 percent. Compared with those before the therapy,
      there were significant differences in aminotransferase, total bilirubin, direct
      bilirubin, PT, PTa and total protein level after treatment (P<0.05 or P<0.01).
      The side-effects were mild. CONCLUSION: Middle artificial liver is effective in
      the treatment of severe hepatitis.

PMID- 14706194
TI  - [Effects of acute hypoxia and intermittent hypoxic acclimatization on
      erythropoietin and hypoxia-inducible factor-1alpha gene expression in rat hepatic
      and renal tissues].
AB  - OBJECTIVE: To explore the effects of acute hypoxia and intermittent hypoxic
      acclimatization on gene expression of erythropoietin (EPO) and hypoxia-inducible
      factor-1alpha (HIF-1alpha) in rat hepatic and renal tissues. METHODS: Twenty-four
      rats (weight was 180 to 220 g) were divided into three groups: normal control
      group (NC), intermittent hypoxic acclimatization (IH) and acute hypoxia groups
      (AH). Gene expression of EPO and HIF-1alpha were examined with Northern dot blot
      method. RESULTS: As compared with NC group, the levels of EPO gene expression in
      rat hepatic and renal tissues in AH group were both significantly elevated
      (P<0.05 or P<0.01). In IH group, the contents of EPO mRNA in hepatic and renal
      tissues were apparently decreased versus AH group (P<0.01), whilst were not
      differently elevated in comparison with group NC (P>0.05). In hepatic tissue from
      AH group, the content of HIF-1alpha mRNA were more than those in NC group and IH
      group, while the levels of gene expression of HIF-1alpha were no substantial
      change in renal tissues from different groups (all P>0.05). CONCLUSION: Hypoxic
      acclimatization can inhibit the increment of EPO gene expression induced by acute
      hypoxia in rat hepatic and renal tissues, in which HIF-1alpha may play important
      roles.

PMID- 14706196
TI  - [Effects of fibroblast growth factor-10 on the secretions of transforming growth
      factor-alpha, platelet-derived growth factor-AB and vascular endothelial growth
      factor by normal adult human keratinocytes in culture].
AB  - OBJECTIVE: To evaluate the effect of fibroblast growth factor-10 (FGF-10) on the
      secretion of transforming growth factor-alpha (TGF-alpha), platelet-derived
      growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) by human
      keratinocytes. METHODS: Concentrations of FGF-10 used were 4, 16, 125 and 500
      ng/ml. Serum-free keratinocyte growth medium without EGF or with EGF were as
      negative control and positive control, respectively. Cells were cultured at 2500,
      37500 cells/cm 2 in dishes in serum-free medium and supernatants were collected
      at 24, 48 and 72 hours. The concentrations of TGF-alpha PDGF-AB and VEGF in cell
      culture supernatant were measured by using TGF-alpha, PDGF-AB and VEGF enzyme
      linked immunoadsorbent assay (ELISA) kits, respectively and cell numbers were
      counted by haemocytometer. RESULTS: For cells cultured at low density and cells
      were subconfluent, TGF-alpha in each group was low and there was no significant
      difference among them at 24 hours. At 48 hours, both in absolute concentrations
      and on a per-cell basis, FGF-10 enhanced the secretion of TGF-alpha by cells
      cultured at low density in a dose-dependent fashion. At 72 hours, the
      concentrations of TGF-alpha in all dose of FGF-10 were significantly higher than
      that in negative control (P<0.05). The production of TGF-alpha in pg/10(6) cells
      in 500 ng/ml FGF-10 reached statistical significance compared with negative
      control (P<0.05). The secretion of TGF-alpha in FGF-10 were lower than that in
      positive control at 48 and 72 hours. For cells cuttured at 37500 cells/cm(2), the
      secretion of TGF-alpha stimulated by FGF-10 was similar to that when cells
      cuttured at lower density. PDGF-AB in each group was undetectable. When cells
      cuttured at high density and reached 100 percent confluent, PDGF-AB could not be
      detected at 24 hours. At 48 hours, both in absolute concentrations and on a per
      cell basis, PDGF-AB productions in 125 and 500 ng/ml of FGF-10 were markedly
      greater than those of negative control at 48 and 72 hours (P<0.05), and the
      secretion of PDGF-AB stimulated by FGF-10 was in a dose-dependent fashion. For
      cells cultured at low density, although the concentrations of VEGF in 16-500
      ng/ml of FGF-10 were significantly higher than that in negative control (P<0.05)
      at 72 hours, on a per-cell basis, they were not greater than that of negative
      control. The secretion of VEGF in positive control was greater than that of FGF
      10 at 24-72 hours. CONCLUSION: The effect of FGF-10 on increasing secretion of
      TGF-alpha and PDGF-AB might mediate the actions of FGF-10 on keratinocytes,
      fibroblasts and endothelial cells to promote re-epithelialization as well as
      granulation tissue deposition during wound healing.

PMID- 14706197
TI  - [Effects of acidi fibroblast growth factor on hepatic and renal functions after
      intestinal ischemia/reperfusion injury].
AB  - OBJECTIVE: To investigate the change in hepatic and renal functions parameters
      after intestinal ischemia-reperfusion (I/R) injury, and to explore the effects of
      acidic fibroblast growth factor (aFGF) on hepatic and renal functions after
      intestinal I/R injury in rats. METHODS: Seventy-eight Wistar rats were divided
      into four groups, which are sham-operated (C) group, ischemia (45 minutes) plus
      reperfusion (R), reconstructive human aFGF treatment (rhF), and wild type aFGF
      treatment (wtF) groups. The animals were sacrificed at 2, 6, 12 and 24 hours,
      respectively. Hepatic and renal functions were analyzed. RESULTS: In comparison
      with those in group C, the hepatic and renal functions were damaged in group R,
      rhF and wtF decreased. Treatment with rhF and wtF markedly abated the hepatic and
      renal dysfunction. The desquamation of intestine villi and infiltration of
      inflammation cells in the submucosa were observed in all groups. CONCLUSION:
      Hepatic and renal functions are damaged after intestinal I/R injury. Treatment
      with rhF and wtF could protect against multiple organ dysfunction associated with
      intestinal ischemia-reperfusiun injury.

PMID- 14706198
TI  - [Radioprotection of recombinant human interleukin-3 and granulocyte-macrophage
      colony-stimulating factor on peripheral lymphocytes of rhesus monkey irradiated
      by 3.0 Gy gamma-rays].
AB  - OBJECTIVE: To observe the radioprotection of recombinant human interleukin-3
      (rhIL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3
      (rhIL-3+GM-CSF) on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy
      gamma-rays, and attempt to provide evidence of cytokines used effectively in the
      therapy of acute radiation sickness. METHODS: Thirty rhesus monkey used in the
      experiment were randomly divided into six groups of rhIL-3 20 microg.kg -1.d -1,
      60 microg.kg -1.d -1 GM-CSF 10 microg.kg -1.d -1 IL-3 20 microg.kg -1.d -1 +GM
      CSF 10 microg.kg -1.d -1 radiation control and normal control. 21 d after whole
      body gamma-irradiation and subcutaneous injection of cytokines, T lymphocyte and
      its subsets, Bax/Bcl-2 proteins in lymphocytes were determined by
      immunohistochemical staining with alkaline phosphatase, and lymphocyte apoptosis
      was detected by TdT-mediated dUTP nick end labeling (TUNEL) technique. RESULTS:
      (1) After irradiation the quantities of peripheral lymphocyte, T cell and its
      subsets obviously decreased as compared with those of normal controls. For
      instance, the percentages of lymphocyte, T, T H and Ts cells in radiation control
      group reduced to 44 percent, 42 percent, 41 percent and 57 percent of normal
      controls, respectively. (2)After radiation the reduction of lymphocyte, T, T H
      and Ts cells were evidently improved by injection of GM-CSF and GM-CSF+IL-3, The
      T,T H cells in GM-CSF and GM-CSF+IL-3 groups were respectively elevated by 1.57
      and 1.76 fold, as well as 1.48 and 1.72 fold of radiation controls. (3) A large
      amount of lymphocyte apoptosis was found after radiation, GM-CSF and GM-CSF+IL-3
      treatment could distinctively inhibit abundant lymphocyte apoptosis induced by
      acute irradiation,the apoptotic rates of lymphocytes in GM-CSF and GM-CSF+IL-3
      groups reduced to 41 percent and 48 percent respectively when compared with that
      of radiation controls. CONCLUSION: A definite dose of GM-CSF and GM-CSF+IL-3
      could suppress the reduction of lymphocyte, T and T H cells and lymphocyte
      apoptosis induced by 3.0 Gy gamma-irradiation. It confirms that inhibition of GM
      CSF and GM-CSF+IL-3 on lymphocyte reduction as well as apoptosis might be one of
      the major causes to alleviate radiation injury of lymphocytes and improve the
      immunological function.

PMID- 14706199
TI  - [Experimental study on prevention and treatment of focal segmental
      glomerulosclerosis with heparin].
AB  - OBJECTIVE: To observe the preventive and therapeutic feasibility of heparin
      calcium injection in rats with focal segmental glomerulosclerosis (FSGS).
      METHODS: Eighteen male Wistar rats were divided into three groups: Normal control
      group (A, n=6), heparin-treated rats (B, n=6) and model group (C, n=6). Rat model
      of FSGS was constructed with low-dose adriamycin, metaraminol and high lipid feed
      method. Group B was treated with heparin. 24-hour urinary protein was measured at
      the 0, 2nd, 4th, 6th and 12th week. Serum total protein, albumin, cholesterol,
      blood urea nitrogen (BUN) and serum creatinine (SCr) were determined at 0, 2nd,
      6th and 12th week. Renal cortex blood flow was performed at the 12th week. Renal
      pathology changes were evaluated at the 12th week as well. RESULTS: 24-hour
      urinary protein was decreased in heparin treatment group after 6th week. The
      serum cholesterol level in heparin treatment group was lower than that in model
      group at 12th week. Renal cortex blood flow was increased significantly in
      heparin -treated group. Glomerular sclerotic index (SI) and glomerular
      extracellular matrix (ECM)/glomerular area (GA) were decreased significantly in
      heparin treatment group. Electron microscopy revealed that there was no
      glomerular capillary cavities obstruction in heparin -treated group, basement
      membrane change and foot precesses fusion were markedly alleviated in comparison
      with model group. CONCLUSION: Heparin may be play a valuable role in the
      prevention and treatment of FSGS.

PMID- 14706200
TI  - [Effect of fructose-1,6-diphosphate and dexamethasone on ischemia/reperfusion
      injury after hemorrhagic shock in rabbits].
AB  - OBJECTIVE: To investigate the mechanism of myocardial ischemia/reperfusion injury
      and the protective effect of fructose-1, 6-diphosphagic (FDP) and dexamethasone
      (DXM) in hemorrhagic shock in rabbits. METHODS: Using a hemorrhagic shock model
      of Wiggers, 48 rabbits were randomly divided into 6 groups. Group I control
      group; GroupII with drugs given before ischemia phase (divided into 3 groups: FDP
      I, DXM I and FDP I+ DXM I); Group III with drugs given in reperfusion phase
      (divided into 2 groups: FDPII and DXMII). The levels of creatine kinase (CK) and
      troponin I (cTnI) in plasma were measured, and myocyte apoptosis index was
      assessed. RESULTS: Baseline levels of CK and cTnI were similar in three groups;
      CK and cTnI and apoptosis index were lower or with a lower tendency in groupII
      and in groupIII (P<0.05 or P<0.01); CK and cTnI showed a lower tendency in rise
      in FDP I and DXM I than in FDPII and even slower in FDP group than in DXM group;
      CK and cTnI levels rose slower in FDP I+DXM I than in FDP I and DXM I.
      CONCLUSION: FDP given during ischemia and DXM could effectively protect the
      myocardium from reperfusion injury following hemorrhagic shock.

PMID- 14706201
TI  - [Significance of changes in plasma lipid peroxide levels in critically ill
      patients after liver transplantation].
AB  - OBJECTIVE: To investigate the relationship between plasma lipid peroxide (LPO)
      levels and prognosis in critically ill patients after liver transplantation.
      METHODS: Plasma LPO levels were measured in 18 patients within 21 days after
      liver transplantation, and their relations to the prognosis were analyzed.
      RESULTS: Plasma LPO levels were markedly elevated in patients before state of
      illness got severe, especially in those with fatal outcome. The peak LPO levels
      were much higher in non-survivors than in survivors, and mortality rate in
      patients whose plasma LPO exceeding 10 micromol/L (5/6 cases) was significantly
      higher than those under 10 micromol/L (1/12 cases, P<0.01). The mortality rate in
      patients with daily fluctuation range of plasma LPO levels over 1.2 micromol.L(
      1).d(-1) was higher than those under 1.2 micromol.L(-1).d(-1), and the difference
      was significant between two groups (P<0.01). CONCLUSION: Measurement of plasma
      LPO level might be of clinical significance to properly judge the critically ill
      conditions, and it can be used as routine examination for patients after liver
      transplantation.

PMID- 14706202
TI  - [Study of mechanism on loss of some components from basement membrane in
      epithelial-interstitial junction in cutaneous pseudoepitheliomatous hyperplasia
      lesion].
AB  - OBJECTIVE: To investigate the relationship between the formation of
      pseudoepitheliomatous hyperplasia (PEH) and the mechanism of loss of some
      components from the basement membrane in epithelial interstitial junction (EIJ)
      in the treatment of cutaneous wounds, when formation of PEH lesion was induced.
      METHODS: Morphological change in epithelial tissue was observed with
      histopathologic method and electronic microscopy in 11 specimens of PEH lesions
      and 6 specimens of normal skin adjacent to PEH (PEH-N) from 11 patients with
      injured skin. The expression characteristics and distribution of pan-cytokeratin
      (p-CK), matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9, proliferating cell
      nuclear antigen (PCNA), epithelial cadherin(E-Cad) and beta-catenin(beta-Cat) in
      EMJ were detected with immunohistochemical methods. RESULTS: Epithelial cells
      expressing P-CK presented squamous epithelialization and extended into deep layer
      of mesenchyma. In epithelium-mesenchyma junction, where IV type collagen and
      laminin were weakly expressed, the protein contents of p-CK, E-Cad, MMP-2, MMP-3
      MMP-9 were decreased, whilst the immunochemical staining of beta-Cat and PCNA was
      apparently increased. In the junction, epithelial basal cells were observed to
      migrate and to depart from basal membrane; epithelial islands and isolated
      epithelial cells expressing p-CK in mesenchyma could be observed. Ultrastructural
      observation revealed deformation of epithelial basal cells, increment of
      nucleus/cytoplasm ratio, loosened intercellular junctions, decrement of
      electronic density of BM and derangement of BM structure could be observed.
      CONCLUSION: Reduction in the capability of epithelial basal cells adhesion,
      differentiation and formation of basement membrane and cytokeratin in PEH
      associated with wound may be the crucial cause which controls epithelial cells
      migration into mesenchyma. That the contents of ColIV and LN were decreased may
      not be associated with MMPs, but with enhancement of the ratio of beta-Cat/E-Cad
      signal might be the important mechanism of dedifferentiation of epithelial basal
      cells and the loss of ability of structure formation and cellular migration.

PMID- 14706203
TI  - [Protective effect of propofol on liver during ischemia-reperfusion injury in
      patients undergoing liver surgery].
AB  - OBJECTIVE: To explore the protective effect of propofol on liver during hepatic
      ischemia/reperfusion injury (HIRI) and its mechanisms in patients undergoing
      liver surgery. METHODS: Eighteen patients who were scheduled for selective
      hepatic surgery were randomly divided into control group (n=9) and propofol
      treatment group (n=9). Changes of several parameters in plasma and effects of
      propofol on them were observed before liver ischemia, at end of ischemia and at
      reperfusion for 25 minutes, parameters of which included superoxide dismutase
      (SOD), xanthine oxidase (XO), lipid peroxide (LPO) and alanine aminotransferase
      (ALT) activity, and the ultrastructure changes in liver tissue were observed
      under electron microscope at 25 minutes after reperfusion. RESULTS: SOD activity
      decreased remarkably (P<0.01); XO activity, LPO concentration and ALT value
      increased significantly (P<0.01) during HIRI, and there were abnormal changes of
      the hepatic ultrastructure at 25 minutes after reperfusion. Afer treatment with
      propofol, the variation of all parameters were alleviated markedly (P<0.05 and
      P<0.01). CONCLUSION: Propofol has protective effects on HIRI by reducing oxygen
      free radical level and inhibiting lipid peroxidation after hepatic
      ischemia/reperfusion in patients undergoing liver cancer surgery.

PMID- 14706204
TI  - [Influence of inhibitors of nitric oxide synthase and L-arginine on the survival
      rate in a rat model of traumatic shock].
AB  - OBJECTIVE: To investigate the influence of inhibitors of nitric oxide synthase
      (NOS) and L-arginine on the survival rate in a rat model of traumatic shock.
      METHODS: A rat model of traumatic shock was established by fracturing the
      posterior limb of the rat. Nomega-nitro-L-arginine-methyl ester (L-NAME, non
      selective NOS inhibitor, 10 mg/kg), amino- guanidine (AG, selective inducible
      nitric oxide synthase (iNOS) inhibitor, 100 mg/kg) and L-arginine (L-Arg, the
      precursor of nitric oxide (NO) synthesis 100 mg/kg) were injected intravenously
      during resuscitation,survival time and survival rate were observed. RESULTS:
      There were no significant changes in survival time and 24-hour survival rate
      between L-NAME ((23.80+/-9.09) hours and 40 percent) and control group (18.78+/
      4.64)hours and 10 percent, both P>0.05); the survival time of AG group (28.72+/
      6.25) hours and L-Arg group (30.64+/-8.77) hours prolonged apparently (both
      P<0.01), and 24-hour survival rate was also increased (both 80 percent, both
      P<0.01). CONCLUSION: Selective iNOS inhibitor AG and L-Arg exert beneficial
      effects on after traumatic shock rats.

PMID- 14706205
TI  - [Effects of L-arginine on the function of platelet aggregation during hepatic
      ischemia/reperfusion injury].
AB  - OBJECTIVE: To explore the effects of L-arginine (L-Arg) on the function of
      platelet aggregation during hepatic ischemia-reperfusion injury (HIRI). METHODS:
      The changes in maximum aggregating rate of circulating platelets (Pt(max)), its
      maximum aggregating time (PtT) as well as its aggregating slopes (PtS) were
      measured. Effects of L-Arg on those parameters were observed during HIRI in 20
      rabbits and 18 patients who were scheduled for elective hepatic surgery. RESULTS:
      Pt max and PtS all increased significantly (P<0.05 and P<0.01), while PtT
      decreased remarkably (both P<0.05) during HIRI of rabbits and patients. After
      treatment with L-Arg, the abnormal changes of parameters as above were all
      alleviated remarkably (P<0.05 and P<0.01). CONCLUSION: It is indicated that L-Arg
      can effectively regulate the function of platelet aggregation during HIRI.

PMID- 14706212
TI  - Does early treatment of ocular myasthenia gravis with prednisone reduce
      progression to generalized disease?

PMID- 14706213
TI  - Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon?
AB  - Characteristic pathological features of multiple sclerosis (MS) include
      inflammation, demyelination and axonal and oligodendrocyte loss. In addition,
      lesions can also have a significant vascular component. In this review,
      morphological, biochemical and radiological evidence is presented suggesting
      angiogenesis as a potential focus for investigation in MS. We hypothesize that
      angiogenesis plays a significant role in the MS lesion, perpetuating disease
      progression. Thus, treatment strategies that inhibit angiogenesis may decrease
      clinical and pathological signs of disease. Several approaches for testing this
      hypothesis are outlined.

PMID- 14706214
TI  - The effect of prednisone on the progression from ocular to generalized myasthenia
      gravis.
AB  - Fifty percent of ocular myasthenia gravis (OMG) patients will progress to
      generalized myasthenia, 90% within 3 years from the onset of ocular symptoms.
      This study was performed to determine whether treatment with oral prednisone
      initiated and completed within 2 years from the onset of ocular symptoms would
      affect the progression of ocular myasthenia to generalized myasthenia gravis
      (GMG). Fifty-six patients were included in this review, with 27 patients in the
      prednisone-treated group and 29 patients in the untreated group. The treated
      group was initiated on 60 mg of prednisone daily with a slow taper over 3-6
      months. At 2 years, significantly fewer patients in the treated group (3 of 27)
      progressed to generalized myasthenia when compared to the untreated group (10 of
      29) (chi(2), p=0.04). Our results suggest that the early use of steroids may
      decrease progression of ocular to generalized myasthenia gravis. The decision to
      use steroids should be considered early in the course of patients diagnosed with
      ocular myasthenia gravis. This study should be considered preliminary and a
      prospective trial is warranted to confirm our observations.

PMID- 14706215
TI  - Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain
      capillary endothelial cells.
AB  - Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic
      lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial
      expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen
      activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary
      endothelial cells (BEC) incubated with MM-LDL (25 microg/ml) for 24 h showed
      increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA
      levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels
      increased two-fold (16.8+/-7.6 vs. 7.6+/-2.1 ng/ml, p<0.05), whereas tPA protein
      levels decreased by 45% (1.3+/-0.5 ng/ml vs. 2.3+/-0.7 ng/ml, p<0.05), and TM
      protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity
      was increased 35% (18.4+/-5.0 vs. 24.8+/-5.2 AU/ml, p<0.05), while TM activity
      was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on
      brain capillary endothelial cells, reducing both endothelial fibrinolytic
      capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function
      (downregulating TM). These results suggest that MM-LDL may contribute to thrombus
      formation in the brain.

PMID- 14706217
TI  - Early neurological deterioration represents recurrent attack in acute small non
      lacunar stroke.
AB  - The aim of this study was to identify the frequency and possible pathogenic
      mechanisms of early neurological deterioration in patients with acute small non
      lacunar infarction. We studied 46 patients (35 men, 11 women; age, 70.3+/-10.4
      years) with acute small non-lacunar infarction. Small non-lacunar infarction was
      diagnosed using diffusion-weighted magnetic resonance imaging (DWI) as being <15
      mm in diameter and located in the cortex and centrum ovale in the middle cerebral
      artery territory. The patients were divided into two groups; Group D (n=6) had
      neurological deterioration within 7 days after symptom onset, while Group N
      (n=40) did not have any neurological deterioration. In Group D, the interval from
      symptom onset to clinical deterioration was 3.3+/-1.5 days (range 2-6 days).
      Blood pressure on admission was higher in Group D than in Group N (p<0.05). In
      Group D, four of these five patients with follow-up DWI had new acute small
      ischemic lesions in addition to the initial lesions, indicating recurrent attacks
      of brain infarction. Neurological deterioration occurred within 7 days after
      symptom onset in 13% of patients. Neurological deterioration was frequently
      caused by recurrent infarction detected by DWI.

PMID- 14706216
TI  - Muscular dystrophy with truncated dystrophin in a family of Japanese Spitz dogs.
AB  - Muscular dystrophy was diagnosed in seven male Japanese Spitz dogs with clinical
      signs of slowly progressive exercise intolerance, generalized weakness, myalgia,
      difficulty chewing and dysphagia. Serum creatine kinase (CK) concentrations were
      markedly elevated. Histopathology showed degeneration and regeneration of muscle,
      consistent with a dystrophic phenotype. Immunohistochemical staining for
      dystrophin and related proteins showed no staining with a monoclonal antibody
      against the rod domain of dystrophin but near-normal staining with an antibody
      against the C terminus. Immunoblot analysis in two affected dogs showed a
      truncated dystrophin protein of approximately 70-80 kDa. The severity of disease
      showed that this fragment was not large enough to protect from the dystrophic
      process.

PMID- 14706218
TI  - Perineurial cell basement membrane thickening and myelinated nerve fibre loss in
      diabetic and nondiabetic peripheral nerve.
AB  - Diabetic neuropathy is associated with changes in the extracellular matrix of the
      perineurium, including thickening of the basement membrane of the perineurial
      cells. Peripheral vascular disease (PVD) is a common vascular condition that can
      occur in the absence or presence of diabetes. Thickening of the vascular basement
      membrane of the vasa nervorum is associated with both diabetes and nondiabetic
      peripheral vascular disease. However, perineurial cell basement membrane (PCBM)
      thickening in the nondiabetic PVD state has not, until now, been investigated. In
      this study, 36 nerve fascicles were examined from three patient groups: a
      diabetic group, a nondiabetic PVD group, and a group free of both PVD and
      diabetes (control group). PCBM thickness, fascicle size, and myelinated nerve
      fibre (MNF) density were measured in all three groups. Endoneurial blood vessels
      were also observed for evidence of morphological changes. The results showed that
      the thickness of the PCBM is significantly greater in the diabetic group in
      comparison with both the control and the nondiabetic PVD group, and this increase
      in thickness is linearly related to fascicle size. The thickness of the PCBM was
      not significantly different between the nondiabetic PVD and control groups.
      Although both the nondiabetic PVD and diabetic groups showed a loss of myelinated
      nerve fibres in comparison with the control group, this loss was statistically
      greater in the diabetic group. The endoneurial blood vessels of both the diabetic
      and nondiabetic PVD groups showed evidence of endothelial cell hyperplasia,
      hypertrophy, and basement membrane reduplication.

PMID- 14706219
TI  - Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations.
AB  - BACKGROUND: Hashimoto's encephalopathy (HE) is a condition believed to complicate
      Hashimoto's thyroiditis (HT). The diagnosis is suspected in the presence of high
      levels of serum anti-thyroid antibodies. We have recently demonstrated that in
      patients with HE there is an intrathecal synthesis of anti-thyroid antibodies,
      and concluded that the diagnosis of HE should be based on this cerebrospinal
      fluid (CSF) finding. OBJECTIVE: getting an estimate of the prevalence of the
      disease, verifying the association with HT and investigating the pathogenetic
      role of anti-thyroid antibodies. METHODS: 34-months prospective study in a
      hospital setting serving a community of 150,000 people. Patients with unexplained
      symptoms of acute or subacute encephalopathy or myelopathy or with a history of
      thyroid disorders were selected for the measurement of anti-thyroid antibodies.
      In the presence of high serum levels of autoantibodies, the same tests were
      performed in the CSF. RESULTS: Twelve patients had increased concentrations of
      serum autoantibodies but HE was diagnosed only in nine patients. The estimated
      prevalence of HE is 2.1/100,000. Only six HE patients had also HT. Four patients
      received corticosteroids, five patients were not treated. Five patients improved,
      four patients spontaneously, one patient after corticosteroids. Repeated CSF
      examinations showed that the titer of CSF autoantibodies did not correlate with
      the clinical stage of the disease nor was influenced by corticosteroids. In
      addition, the course of symptoms was independent of therapy. CONCLUSIONS: The
      association of encephalopathy and high titers of anti-thyroid antibodies is not
      sufficient to make a diagnosis of HE. Independent of the clinical status of the
      thyroid gland, the intrathecal synthesis of autoantibodies is a distinctive
      marker of this elusive condition.

PMID- 14706220
TI  - Multiple risk factors for Parkinson's disease.
AB  - OBJECTIVE: To determine the relative contribution of various risk factors to the
      development of Parkinson's disease (PD). METHODS: Ten variables that were
      independently associated with PD in a health system population-based case-control
      study of epidemiological risk factors for the disease were jointly assessed.
      Stepwise logistic regression, adjusted for sex, race and age was used to develop
      a multiple variate model that best predicted the presence of PD. The population
      attributable risk was estimated for each variable in the final model, as well as
      for all factors together. RESULTS: The 10 initial variables included >20 years
      occupational exposure to manganese or to copper, individually; >20 years joint
      occupational exposure to either lead and copper, copper and iron, or lead and
      iron; a positive family history of PD in first- or second-degree relatives;
      occupational exposure to insecticides or herbicides; occupational exposure to
      farming; and smoking. Logistic regression resulted in a final model that included
      >20 years joint occupational exposure to lead and copper (p=0.009; population
      attributable risk [PAR]=3.9%), occupational exposure to insecticides (p=0.002;
      PAR=8.1%), a positive family history of PD in first- and second-degree relatives
      (p=0.001; PAR=12.4%), and smoking </=30 pack-years or not smoking (p=0.005;
      PAR=41.4%). All four variables combined had a PAR=54.1%. CONCLUSIONS: Our final
      model of PD risk suggests that occupational, environmental lifestyle and, likely,
      genetic factors, individually and collectively, play a significant role in the
      etiology of the disease. Clearly, additional risk factors remain to be determined
      through future research.

PMID- 14706221
TI  - Serum-cortisol reflects severity and mortality in acute stroke.
AB  - BACKGROUND: The adrenal glucocorticoid stress response in humans causes
      catabolism, increasing blood glucose and heart rate, and possibly potentiates
      ischaemic damage to neurons. These effects could induce secondary brain damage in
      acute stroke. MATERIALS AND METHODS: This prospective study was based on a single
      determination of s-cortisol in 172 patients included within 24 h of stroke onset,
      50% within 12 h of stroke onset. All patients were admitted to hospital within 6
      h of stroke onset. We investigated the relations of s-cortisol to neurological
      deficit measured by Scandinavian Stroke Scale (SSS), lesion volume on CT-scan,
      blood glucose on admission, pulse rate, blood pressure, body temperature,
      deteriorating stroke, cytokines and cytokine receptors, and outcome. RESULTS: In
      a multivariate logistic regression analysis, s-cortisol was independently related
      to death within 7 days of stroke onset, odds ratio (OR) Cortisol(+100 nmol/l) 1.9
      (95% CI 1.01-3.8); serum-cortisol was, however, not a predictor of death or
      dependency within 3 months. S-cortisol correlated to SSS (rho=-0.45, p<0.001),
      body temperature (rho=0.27, p<0.001), pulse rate (rho=0.26, p<0.001), and lesion
      volume (rho=0.33, p<0.001). S-cortisol was related to the presence of insular
      damage. CONCLUSION: Acute stroke mortality related to increasing serum-cortisol
      levels. S-cortisol was associated with stroke severity and markers reflecting
      stroke severity.

PMID- 14706222
TI  - Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies
      is significantly associated to a subset of multiple sclerosis patients with
      progressive forms.
AB  - The purpose of this study was to provide further insight into the effective
      relevance of the association between Chlamydia pneumoniae and MS. We evaluated by
      ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae
      IgG in 46 relapsing-remitting (RR), 14 secondary progressive (SP) and 11 primary
      progressive (PP) MS patients grouped according to clinical and Magnetic Resonance
      Imaging (MRI) evidence of disease activity. Fifty-one patients with other
      inflammatory neurological disorders (OIND) and 52 with non-inflammatory
      neurological disorders (NIND) were used as controls. A C. pneumoniae-specific
      intrathecal IgG synthesis as detected by the relative specific index was present
      in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was
      significantly more frequent in MS and in OIND than in NIND (p<0.001) and in SP
      and PP MS than in RR MS patients (p<0.02). Among the patients with C. pneumoniae
      specific intratecally produced antibodies, CSF high-affinity anti-C. pneumoniae
      IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in
      RR MS and NIND patients. These findings confirm that the presence of a humoral
      immune response to C. pneumoniae within the central nervous system (CNS) is not
      selectively restricted to MS, but is shared by several inflammatory neurological
      conditions. In addition, our results suggest that an intrathecal production of C.
      pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS
      progressive forms in which a C. pneumoniae brain chronic persistent infection may
      play an important pathogenetic role.

PMID- 14706223
TI  - In vitro effects of D-2-hydroxyglutaric acid on glutamate binding, uptake and
      release in cerebral cortex of rats.
AB  - Neurological dysfunction is common in patients with D-2-hydroxyglutaric aciduria
      (DHGA). However, the mechanisms underlying the neuropathology of this disorder
      are far from understood. In the present study, we investigated the in vitro
      effects of D-2-hydroxyglutaric acid (DGA) at various concentrations (0.1-1.0 mM)
      on various parameters of the glutamatergic system, namely the basal and potassium
      induced release of L-[3H]glutamate by synaptosomal preparations, Na(+)-dependent
      L-[3H]glutamate uptake by synaptosomal preparations and Na(+)-independent L
      [3H]glutamate uptake by synaptic vesicles, as well as of Na(+)-independent and
      dependent L-[3H]glutamate binding to synaptic plasma membranes from cerebral
      cortex of male adult Wistar rats. We observed that DGA significantly increased
      synaptosomal L-[3H]glutamate uptake, without altering the other parameters.
      Although these findings do not support a direct excitotoxic action for DGA since
      the metabolite did not affect important parameters of the main neurotransmission
      system, they do not exclude a direct action of DGA on NMDA or other glutamate
      receptors. More comprehensive studies are therefore necessary to evaluate the
      exact role of DGA on neurotransmission.

PMID- 14706224
TI  - Cutaneomuscular reflexes following stroke: a 2-year longitudinal study.
AB  - Cutaneomuscular reflex responses (CMRs) have been studied in nine stroke patients
      (55-84 years) starting from the first 1-7 weeks after stroke and continuing at
      intervals of 6-8 weeks for up to 2 years. Multi-unit surface EMG signals were
      recorded from the stroke and non-stroke first dorsal interosseous (1DI) hand
      muscle while subjects gripped a dowel, and concomitant stimulation of the digital
      nerves of the index finger was delivered at 2.5 x threshold for perception. Motor
      function was measured using the Motor Assessment Scale (MAS) and patients were
      classified as having a good or a poor recovery according to their final
      functional outcome. None of the patients showed a change in the sizes of the E1,
      I1 and E2 reflex components over time. At initial testing, the size of the E1
      component for all patients who showed good recovery fell within the 95% reference
      range (0-16.5% modulation of background EMG) found for normal age matched
      controls. In contrast, when first tested, 5/5 patients who showed no significant
      recovery over the 2-year period, had exaggerated spinal E1 components greater
      than 16.5%. We conclude that exaggerated E1 components could be predictive of a
      poor functional outcome at 2 years.

PMID- 14706225
TI  - Enhanced intracortical inhibition in cerebellar patients.
AB  - OBJECTIVE: The aim of the study was to examine intracortical excitability in
      cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long
      latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to
      paired transcranial magnetic stimulation (TMS) were investigated in 8 patients
      with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The
      conditioning stimulus for short-latency intracortical inhibition and
      intracortical facilitation was set at 70% of the resting motor threshold (RMT)
      and preceded the test stimulus (110-120% of the resting motor threshold) by
      interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical
      inhibition determinations, the conditioning stimulus was set at 120% of the
      resting motor threshold and preceded the test stimulus (also 120% of the resting
      motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No
      statistically significant differences were found between patients and controls as
      regards either short-latency intracortical inhibition or intracortical
      facilitation. A significant prevalence of long-latency intracortical inhibition
      was present in cerebellar patients at interstimulus intervals of 200-500 ms
      (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of
      test MEP). The amplitude of conditioned MEPs was persistently less than 45% of
      the test MEP in six patients, who were studied at interstimulus intervals up to
      1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and
      abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation
      of GABAergic interneurons in the motor cortex of patients may be the mechanism
      responsible for this abnormality. Our findings seem to be specific to cerebellar
      diseases and are the opposite of those found in movement disorders such as
      dystonia and Parkinson's disease. These data suggest that the cerebellum and the
      basal ganglia may have opposite influences in tuning the excitability of the
      motor cortex.

PMID- 14706226
TI  - Depressive symptoms account for deficient information processing speed but not
      for impaired working memory in early phase multiple sclerosis (MS).
AB  - Depressive symptoms may influence neuropsychological functioning negatively. A
      substantial proportion of multiple sclerosis (MS) patients exhibit
      neuropsychological impairments and depressive symptomatology is more common in MS
      as compared to healthy controls and to other neurological diseases. The
      objectives of the present study were to assess information processing speed,
      working memory and executive functions in early phase MS and to investigate
      whether severity of depressive symptoms account for these aspects of cognition in
      MS. The patients show slowed information processing speed and impaired working
      memory, whereas executive functioning, as measured with the Wisconsin Card
      Sorting Test, is unaffected. Depressive symptoms account for slowed information
      processing speed, but not for impaired working memory.

PMID- 14706227
TI  - Discriminatory features of acute transverse myelitis: a retrospective analysis of
      45 patients.
AB  - Acute transverse myelitis (ATM) is a pathogenetically heterogeneous inflammatory
      disorder of the spinal cord. Therefore, the identification of clinical and
      paraclinical features providing clues of the underlying etiologies is needed. The
      clinical presentation, blood and cerebrospinal fluid (CSF) findings as well as
      magnetic resonance imaging (MRI) and neurophysiological features were
      retrospectively analyzed in 45 unselected consecutive patients with ATM.
      Parainfectious ATM was diagnosed in 38% of patients. The underlying infectious
      agent, however, was identified only in a minority of patients. In 36% of
      patients, the etiology remained uncertain ("idiopathic" ATM) and in 22% ATM was
      the first manifestation of possible multiple sclerosis (ATM-MS) according to
      recently published diagnostic criteria. Spinal cord MRI showed signal alterations
      in 96% of the patients. In ATM-MS, monosegmental involvement of the spinal cord
      was most frequent while spinal cord involvement of two or more segments was more
      common in ATM of other etiologies. Of particular note, neurophysiological
      examinations showed evidence of peripheral nervous system (PNS) involvement in
      27% of patients with ATM but not in patients with ATM-MS. Therefore,
      neurophysiological evidence of PNS involvement may provide additional
      discriminatory features between ATM-MS and ATM of other etiologies.

PMID- 14706228
TI  - Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and
      GalNAc-GD1a.
AB  - This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE)
      associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to
      Campylobacter jejuni enteritis, the patient rapidly developed consciousness
      disturbance and hyperreflexia in addition to external ophthalmoplegia and
      cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic theta activities,
      predominantly in the front-central area. He received high doses of immunoglobulin
      intravenously and had completely recovered 3 months later. High anti-GM1b and
      anti-GalNAc-GD1a IgM antibody titers present during the acute phase decreased
      with his clinical improvement. An absorption study showed the anti-GM1b and anti
      GalNAc-GD1a IgM antibodies to be cross-reactive. Anti-GM1b and anti-GalNAc-GD1a
      antibodies have been detected in some patients who developed Guillain-Barre
      syndrome after C. jejuni enteritis, whereas the anti-GQ1b IgG antibody is
      associated with BBE. Infection by C. jejuni bearing a GM1b-like or GalNAc-GD1a
      like lipooligosaccharide may trigger the production of anti-GalNAc-GD1a and anti
      GM1b IgM antibodies. It is not clear why our patient developed BBE rather than
      Guillain-Barre syndrome. These antibodies may, however, prove useful serological
      markers for identifying BBE patients who do not have the anti-GQ1b IgG antibody.

PMID- 14706229
TI  - Severe bruxism following basal ganglia infarcts: insights into pathophysiology.
AB  - Bruxism characterized by clenching and grinding of teeth can lead to toothwear,
      headaches and depression. While bruxism has been associated with a number of
      neurological diseases, it has not been highlighted following cerebral infarction.
      An elderly man presented with an acute onset of tooth grinding and jaw clenching
      associated with dysarthria. His bruxism was worse during the day and resolved
      during sleep. He had frequent jaw aches, headaches and swallowing difficulty.
      Examination demonstrated the presence of dysarthria with jaw clenching and tooth
      grinding, producing persistent high pitch and loud squeaky sounds. A magnetic
      resonance imaging and angiography examination revealed a recent infarct in the
      right thalamus. In addition, chronic lacunar infarcts were present in the
      bilateral caudate nuclei with severe basilar artery stenosis. He was successfully
      treated with botulinum toxin. We discuss the pathophysiologic mechanisms of
      bruxism associated with basal ganglia infarcts. Dysfunction of the efferent
      and/or afferent thalamic or striatopallidal tracts may play a role in bruxism.
      Early recognition of bruxism following stroke could reduce unnecessary suffering
      since the condition can be effectively treated.

PMID- 14706230
TI  - Video-assisted thoracoscopic extended thymectomy and extended transsternal
      thymectomy in non-thymomatous myasthenia gravis patients.

PMID- 14706232
TI  - The expression of early resistance to an infection with Mycobacterium
      tuberculosis by old mice is dependent on IFN type II (IFN-gamma) but not IFN type
      I.
AB  - Old mice can express a transient early resistance to infection with M.
      tuberculosis that requires the presence of CD8 T cells within the lungs. Further
      characterization of those CD8 T cells within the aged lung established that the
      majority of CD8 T cells from old mice expressed the IL-15 receptor (CD122) in
      combination with bright expression of CD44 (CD44(hi)), and were capable of
      producing IFN-gamma after T cell receptor cross-linking. It has been previously
      described that CD8 CD44(hi) T cells proliferate in response to IFN-I, acting via
      IL-15, and therefore we determined whether IFN-I signaling could be a participant
      in the response of CD8 T cells within the lungs of old mice infected with M.
      tuberculosis. We demonstrate here that IFN-I signaling was required for the
      expansion of CD8 T cells within the aging lung in response to infection with M.
      tuberculosis, but that IFN-I signaling had no influence on the capacity of old
      mice to express early resistance to an infection with M. tuberculosis. Resident
      CD8 T cells were still however capable of producing IFN-gamma, which we
      demonstrate here to be critical in the expression of early resistance, suggesting
      that the expression of early resistance requires the participation, but not
      expansion, of the CD8 T cell pool within the aging lung.

PMID- 14706233
TI  - Reduced free-radical production and extreme longevity in the little brown bat
      (Myotis lucifugus) versus two non-flying mammals.
AB  - The extended longevity of bats, despite their high metabolic rate, may provide
      insight to patterns and mechanisms of aging. Here I test predictions of the free
      radical or oxidative stress theory of aging as an explanation for differences in
      lifespan between the little brown bat, Myotis lucifugus (maximum lifespan
      potential MLSP=34 years), the short-tailed shrew, Blarina brevicauda (MLSP=2
      years), and the white-footed mouse, Peromyscus leucopus (MLSP=8 years) by
      comparing whole-organism oxygen consumption, hydrogen peroxide production, and
      superoxide dismutase activity in heart, kidney, and brain tissue. Mitochondria
      from M. lucifugus produced half to one-third the amount of hydrogen peroxide per
      unit of oxygen consumed compared to mitochondria from B. brevicauda and P.
      leucopus, respectively. Superoxide dismutase (SOD) activity did not differ among
      the three species. These results are similar to those found for birds, which like
      bats have high metabolic rates and extended longevities, and provide support for
      the free radical theory of aging as an at least partial explanation for the
      extreme longevity of bats.

PMID- 14706234
TI  - An alpha-tocopherol dose response study in Paramecium tetraurelia.
AB  - Vitamin E (D,L-alpha-tocopherol) was administered to Paramecium tetraurelia in
      doses of 10, 100, 1000 and 10,000mg/l throughout its clonal lifespan. ANOVA
      revealed significant differences in clonal lifespan between groups, whether
      lifespan was measured in total fissions, or in days (P<0.05). When mean clonal
      lifespan was measured in fissions the greatest difference was between the
      1000mg/l alpha-tocopherol treatment at 382 fissions, and the ethanol control at
      255.5 fissions. The greatest difference in mean clonal lifespan in days survived
      was between the 10,000mg/l alpha-tocopherol treatment at 292.5 days and the
      ethanol control at 76 days. ANOVA also revealed significant differences (P<0.05)
      in the initial cell fission rates between groups. At the 1000 and 10,000mg/l
      concentrations of alpha-tocopherol, a decrease in cell fission rates was apparent
      early in the lifespan, but these rates began to increase gradually during the
      late clonal lifespan. Although no clonal toxicity effects were found in terms of
      decreasing life-expectancy, the 1000 and 10,000mg/l treatment groups exhibited
      higher background mortality rates throughout their respective lifespans than did
      the control groups, which could represent a cytotoxic effect.

PMID- 14706236
TI  - Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress.
AB  - The mev-1 gene encodes cytochrome b, a large subunit of the Complex II enzyme
      succinate-CoQ oxidoreductase. The mev-1(kn1) mutants are hypersensitive to
      oxidative stress and age precociously, probably because of elevated superoxide
      anion production in mitochondria. Coenzyme Q (CoQ) is essential for the
      mitochondrial respiratory chain. Here, we show that CoQ(10) and Vitamin E
      extended the life span of wild-type Caenorhabditis elegans. Conversely, only
      CoQ(10) recovered the life shortening effects seen in mev-1. We also show that
      CoQ(10) but not Vitamin E reduced superoxide anion levels in wild type and mev-1.
      Another previously described phenotype of mev-1 animals is the presence of
      supernumerary apoptotic cells. We now demonstrate that CoQ(10) (but not Vitamin
      E) suppressed these supernumerary apoptoses. Collectively these data suggest that
      exogenously supplied CoQ(10) can play a significant anti-aging function. It may
      do so either by acting as an antioxidant to dismutate the free radical superoxide
      anion or by reducing the uncoupling of reactions during election transport that
      could otherwise result in superoxide anion production. The latter activity has
      not been ascribed to CoQ(10); however, it is known that conditions that uncouple
      electron transport reactions can lead to elevated superoxide anion production.

PMID- 14706235
TI  - Transition to an irreversible state of senescence in HeLa cells arrested by
      repression of HPV E6 and E7 genes.
AB  - Inhibition of human papillomavirus (HPV) E6 and E7 transcription by means of the
      E2 protein of bovine papillomavirus 1 (BPV1) has been shown to induce acute
      growth arrest in HPV-positive cervical carcinoma cells. This state of arrest is
      marked by the expression of senescence phenotypes including SA beta-Gal activity
      and lipofuscin accumulation. In this study, we examined the reversibility of
      these phenotypes by exogenously expressing the E6 and E7 genes into HeLa cells
      growth-arrested by the depletion of E6/E7. Re-expression of E7 (but not E6) in 2
      days following E2 transduction induced the cells to resume growth. The
      proliferating cells manifested the phenotype of untreated HeLa cells, suggesting
      that E7 is the major factor responsible for the continued proliferation and the
      suppression of the senescence phenotype in cervical carcinoma cells. However, E7
      in 5 days following E2 transduction did not prevent HeLa cells from entering the
      senescent state, indicating that the arrested state becomes irreversible. Our
      results suggest that, upon depletion of the viral oncoproteins, a senescent state
      is irreversibly induced in HeLa cells after a period of commitment. The status
      and cellular location of certain factors involved in signal transduction and cell
      cycle control was altered as well along with this irreversibility transition.

PMID- 14706237
TI  - Antigen-specific CD4 T cell clonal expansion and differentiation in the aged
      lymphoid microenvironment. I. The primary T cell response is unaffected.
AB  - Aging is associated with changes in the immune system that lead to decreased
      immunity in the elderly. Prior studies from humans and mice have shown that aged
      T cells exhibit numerous defects, including decreased proliferation following in
      vitro stimulation, suggesting that intrinsic defects exist within aged T cells,
      leading to defective T cell activation and clonal expansion. In vivo, however,
      cellular and soluble factors in the lymphoid microenvironment influence T cell
      function. To investigate the effects of the aged lymphoid microenvironment on T
      cell function, we monitored the immune response of CD4 T cells from DO11.10 TCR
      transgenic mice following adoptive transfer into young and aged hosts. After
      immunization with specific antigen similar rates of donor DO11.10 T cell division
      were observed in the two host types. However, at the peak of the response,
      greater numbers of DO11.10 T cells were found in the aged hosts. Regardless of
      the age of the host, the donor DO11.10 T cell population differentiated into
      functional effector cells. Despite the increased CD4 T cell growth in aged hosts,
      similar numbers of memory DO11.10 T cells were found in young and in aged hosts.
      As CD4 T cell clonal expansion and differentiation is not impaired in the aged
      microenvironment, our data suggest that diminished T cell immunity during aging
      is largely due to intrinsic T cell defects, rather than to extrinsic influences
      associated with the aged lymphoid microenvironment.

PMID- 14706238
TI  - Antigen-specific CD4 T cell clonal expansion and differentiation in the aged
      lymphoid microenvironment. II. The memory T cell response is diminished.
AB  - We investigated the ability of the aged host environment to support a memory CD4
      T cell response to a secondary immunization with a specific antigen. Using an
      adoptive transfer model, we previously reported that young CD4 T cells,
      transferred into the young or the aged lymphoid microenvironment, clonally expand
      and differentiate in a similar fashion after primary immunization with a specific
      antigen. In this report, we have monitored the clonal expansion of the donor
      derived memory CD4 T population following a secondary challenge with the specific
      antigen. We show that antigen-specific memory T cell clonal expansion is
      diminished in the aged hosts. However, upon in vitro re-stimulation, antigen
      specific CD4 T cells isolated from young and from aged hosts were equally
      responsive to antigen, thus indicating an inhibitory effect in the aged host
      environment. We provide evidence that factors specifically present in previously
      immunized aged hosts must be responsible for the diminished response of otherwise
      functional, antigen-specific memory CD4 T cells. Our results suggest that the
      decline in immunologic memory to foreign antigens may be due not only to
      intrinsic defects in aged T cells, but also to age-related differences in the
      lymphoid microenvironment of previously immunized hosts.

PMID- 14706239
TI  - Enhanced potential for oxidative stress in livers of senescent rats by the
      peroxisome proliferator-activated receptor alpha agonist perfluorooctanoic acid.
AB  - Aging sensitizes the liver to the hepatocarcinogenic effect of PPARalpha agonists
      via unknown mechanisms. This study was designed to investigate age-dependent,
      hepatic effects of the non-metabolizable PPARalpha agonist perfluorooctanoic acid
      (PFOA) on the delicate balance between activities of pathways involved in
      H(2)O(2) production and elimination. Male Fischer-344 rats, ranging in age from
      juvenile (4 weeks old), post puberty (10 weeks old), mature adulthood (20 weeks
      old), middle age (50 weeks old), to senescence (100 weeks old), were treated
      intragastrically with either 150mg PFOA/kg in 0.5ml corn oil, or with corn oil
      alone. Animals were sacrificed at predetermined time-points ranging from 0-28
      days post PFOA or oil administration. Hepatic peroxisomal beta-oxidizing
      activities were significantly elevated (four- to six-fold) in all age groups by
      PFOA. While levels declined to near basal values within 3-7 days in 4 and 10,
      they remained elevated for an additional week in 20-, 50- and 100-week-old rats.
      However, catalase activity was significantly lower in senescent livers compared
      with all other groups. In conclusion, aging does not appear to hinder the
      capacity of the liver to produce excess H(2)O(2) through peroxisomal beta
      oxidation upon exposure to PPAR agonists. However, the reduced ability of the
      senescent liver to recover from PFOA-induced potential increase in H(2)O(2)
      production, coupled with the apparent diminished capacity of this liver to
      decompose H(2)O(2), enhances the potential for hepatic oxidative damage in aged
      animals. This may explain the enhanced susceptibility of the senescent liver to
      the hepatocarcinogenic effect of PPAR agonists.

PMID- 14706240
TI  - Systemic mechanisms of individual reproductive life history in female Medflies.
AB  - This paper is the second one in a series of two papers hypothesizing and testing
      systemic grounds of reproductive life history in the female fruit fly. In the
      first paper, we analyzed mechanisms of individual fecundity scheduling and have
      drawn the following conclusions. Individual fecundity in female flies is endowed
      as a flat pattern with a steady-state period of a constant rate of egg-laying. An
      individual female reveals three stages in her adult life history: maturation,
      maturity, and senescence. The first stage is a transient period of achieving a
      steady state at maturity, which can be maintained until the senescence stage.
      Thus, an individual fecundity pattern has no maximum. The maximums observed
      experimentally are averaging-caused artifacts. Two natural causes of deaths exist
      in flies, senescence-caused ones and premature deaths, probably due to a
      reproductive overload. In this paper, to confirm these findings, we use
      individual daily scores of egg-laying in four populations of Mediterranean fruit
      flies. Based on fecundity scores, we divide each Medfly population into four
      classes, namely zero-egg, short-, medium- and long-lived egg-layers. We
      demonstrate that, indeed, the three above findings definitely exist in Medflies.
      Our procedure allows the efficient storage of individual fecundity in parametric
      form, with only five numbers for each fly. Finally, this protocol will allow a
      more precise analysis of fecundity-energy trade-offs in flies carrying
      appropriate longevity mutations.

PMID- 14706241
TI  - SolEmuls-novel technology for the formulation of i.v. emulsions with poorly
      soluble drugs.
AB  - Intravenously injectable o/w emulsions of drugs being poorly soluble in water and
      simultaneously in oils need to be produced by locating the drug in the
      interfacial lecithin layer, e.g. amphotericin B. For achieving this, up to now
      organic solvents were required. The objective was to develop a solvent-free
      production method for such emulsions. Drug and the pre-formed parenteral emulsion
      Lipofundin were mixed and subjected to high pressure homogenisation. Drug powder
      and emulsions were characterised regarding size and physical stability by photon
      correlation spectroscopy (PCS), laser diffractometry (LD) and zeta potential
      measurements. Drug incorporation was studied using light microscopy, electron
      microscopy (EM) and a centrifugation test to separate non-dissolved drug.
      Amphotericin B and carbamazepine were used as model drugs. The high streaming
      velocities lead to accelerated drug dissolution and partitioning into the
      interfacial layer (so-called "solubilisation by emulsification", SolEmuls
      Technology). The interfacial layer could incorporate (solubilise) a certain
      amount of drug, revealed by EM pictures. Exceeding this concentration, hybrid
      dispersions were formed consisting of drug-loaded oil droplets and drug
      nanocrystals of similar size (approximately 200 nm). Both dispersion types are
      i.v. injectable opening the opportunity to deliver the drug in a concentrated
      form at desired low injection volume, e.g. 10 mg/ml.

PMID- 14706242
TI  - In vitro evaluation of intestinal absorption of desmopressin using drug-delivery
      systems based on superporous hydrogels.
AB  - The aim of this study was to investigate and modify the potential of drug
      delivery systems based on superporous hydrogel (SPH) for improving the intestinal
      transport of the peptide drug desmopressin in vitro. The swelling properties and
      mechanical strength of SPHs were studied. The release profile of desmopressin was
      investigated by changing the composition of excipients in the formulations.
      Subsequently, the ability of the SPH-based drug-delivery systems to enhance the
      transport of desmopressin across porcine intestine was performed in vitro. The
      swelling properties and mechanical strength of SPHs were affected by the addition
      of the disintregrant AcDiSol. This disintregrant reduced the swelling ratio to
      10% and the time to 80% swelling was retarded by 3-5 min in comparison to the
      negative control. AcDiSol increased the mechanical strength, according to the
      increasing of penetration pressure value, the pressure that the punch can
      penetrate the gel, of the SPHs. The transport of desmopressin across the
      intestinal mucosa in vitro was enhanced four- and six-fold by applying SPH, with
      AcDiSol, in the absence and presence of the additional absorption enhancer
      trimethyl chitosan chloride, respectively, in comparison to the negative control.
      It is concluded that drug-delivery systems based on SPHs are promising for
      enhancing the intestinal absorption of desmopressin.

PMID- 14706243
TI  - A microdialysis model to examine nasal drug delivery and olfactory absorption in
      rats using lidocaine hydrochloride as a model drug.
AB  - Targeting of the central nervous system by direct drug transport from the nose to
      the brain has gained increased attention through the last decade. In the present
      study, a model for olfactory drug absorption has been investigated using
      intravenous and unilateral nasal administration of lidocaine hydrochloride in
      rats. To investigate the possible drug delivery aspects of this route of
      transport to a central part of the brain a microdialysis model using in vivo
      recovery by calibrator was applied to the systemic blood and to right and left
      striatum. The integrity of the blood-brain barrier was evaluated following
      microdialysis probe implantation. The in vivo experiments were carried out as a
      cross-over study in rats. The drainage from the nasal cavity was not restricted
      by occlusion. It was found that true unbound lidocaine concentrations could be
      calculated from in vivo recovery measurements of retrodialysis of prilocaine
      hydrochloride. The relative in vivo recoveries in striatum (11.3%) and blood
      (24.0%) were significantly lower than in vitro (31.3 and 44.9%). The blood-brain
      barrier was found to retain its physical integrity when evaluated one hour after
      probe implantation. From pharmacokinetic modelling of the time-concentration
      curves it was found that the absorption rates and area under the curve (AUC)
      values of lidocaine in left and right striatum were not statistically different
      following nasal and intravenous administration, respectively. The average nasal
      bioavailabilities of lidocaine in blood, left and right striatum were 85, 103 and
      129%, respectively. It was concluded that no significant olfactory absorption to
      striatum was evident in the present study. However, the method should be
      applicable to studies of drug delivery to blood and brain following nasal
      administration of other drugs.

PMID- 14706244
TI  - Comparison of Franz cells and microdialysis for assessing salicylic acid
      penetration through human skin.
AB  - The purpose of the present study was to compare Franz cells (FC) and
      microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The
      influence of pH on SA flux was also assessed by these two techniques. Excised
      abdominal human skin was used in the experiments. SA was dissolved in phosphate
      buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC
      solutions and in MD samples were assessed by high performance liquid
      chromatography (HPLC). The results demonstrate that the flux of SA decreased with
      increased pH. The profiles permeation determined by Franz cells and microdialysis
      were similar. However, whatever the pH, the SA flux was higher with microdialysis
      than with Franz cells. The results showed that SA percutaneous permeation
      conformed to the pH partition hypothesis. The flux of SA was different when it
      was determined by the two techniques. The collect of SA, by these two techniques
      is different. The results of the two techniques are compared and discussed.

PMID- 14706245
TI  - Application of dynamic mechanical analysis (DMA) to determine the mechanical
      properties of pellets.
AB  - Pellets of a wide range of mechanical properties were produced by the process of
      extrusion and spheronisation using various formulation factors. A range of
      mechanical properties from a simple fracture load to detailed load/displacement
      curves obtained when pellets were subjected to diametral compression test and a
      bed of pellets was compacted, were used to provide measure of tensile strength,
      deformability, linear strain, elastic modulus, yield and shear strength. Such
      conventional techniques resulted in irreversible damage to the structure of the
      pellets and were unable to establish the viscoelastic properties of the pellets.
      The application of the dynamic mechanical analysis (DMA), however, allowed the
      determination of (1) an accurate Young's modulus of elasticity, which was found
      to be between 8.4 and 24-fold higher than that determined from the diametral
      compression test, (2) the presence of a reversible elastic deformation even after
      the yield point in terms of storage modulus and (3) a change in the values of the
      phase angle, which illustrates the increase in viscoelasticity of the pellets
      formed with ethanol, glyceryl monostearate (GMS) or glycerol, while a decrease in
      viscoelasticity with the incorporation of lactose into the microcrystalline
      cellulose (MCC) pellets. This work further demonstrated that the only feasible
      technique for determining the elastic and plastic deformability of the pellets is
      the one which subjects the specimen to stress/relaxation cycles and can determine
      the dissipated energy in terms of loss modulus or phase angle, and that is DMA.

PMID- 14706246
TI  - Polymers-gamma ray interaction. Effects of gamma irradiation on modified release
      drug delivery systems for oral administration.
AB  - The aim of this work is to verify the efficiency of two kinds of matrix tablets
      formulations containing PEO or PVA as retarding polymer. Moreover, since in the
      last years the exposure to ionizing radiation is a more and more used method to
      reduce bacterial charge in pharmaceutical products, the effects of gamma
      irradiation on these two kinds of polymers has been evaluated. The study is
      performed on matrix tablets containing diltiazem HCl, as model drug, and
      polyethylene oxides (PEO) of two different molecular weights or polyvinylalchool
      (PVA) of medium degree of hydrolysis, as drug release modulators. Dissolution of
      the matrices, release of diltiazem and morphological behaviour of the samples,
      before and after exposure to increasing doses of gamma irradiation, are
      investigated in order to verify their stability. The results show that the
      ionizing radiation does not modify significantly the dissolution trend of the PVA
      samples; on the contrary, the dissolution and the morphological behaviour of the
      PEO matrices is strongly affected by the radiation dose received. In particular,
      the dissolution rate of the irradiated PEO tablets dramatically increases as a
      function of the irradiation dose and the swelling process, which characterised
      the non-irradiated PEO samples, was replaced by a rapid erosion process
      responsible for the quickly dissolution of the matrices. The changes of the
      dissolution and morphological PEO tablets performances could be explained by a
      breaking of the polymeric chains (shown by EPR studies) as a consequence of the
      exposure to gamma rays. These chemical-structural modifications of the polymers
      are responsible for the reduced efficacy of the PEO systems in controlling the
      drug release rate.

PMID- 14706247
TI  - A simple relationship between dielectric constant of mixed solvents with solvent
      composition and temperature.
AB  - A simple computational method for calculating dielectric constants of solvent
      mixtures based on Redlich-Kister extension was proposed. The model was applied to
      the experimental dielectric constant of binary and ternary solvent mixtures at
      fixed and/or various temperatures and showed accurate results. Overall average
      percentage deviation (OAPD) between calculated and experimental dielectric
      constants was calculated as an accuracy criterion. The OAPDs for correlative and
      predictive analyses of dielectric constants in binary solvents at a fixed
      temperature were 0.56 and 1.42%, respectively. The corresponding values for
      binary solvents at different temperatures were 1.29 and 1.92%, respectively. The
      OAPDs for correlative and predictive analyses of dielectric constants of a
      nonaqueous ternary solvent mixture at various temperatures were 1.61 and 3.05%.
      The accuracy of the proposed models has also been compared with those of
      previously published models and results showed that the proposed models were
      superior and capable of providing more accurate results.

PMID- 14706248
TI  - An investigation of calibration methods for solution calorimetry.
AB  - Solution calorimetry has been used in a number of varying applications within
      pharmaceutical research as a technique for the physical characterisation of
      pharmaceutical materials, such as quantifying small degrees of amorphous content,
      identifying polymorphs and investigating interactions between drugs and
      carbohydrates or proteins and carbohydrates. A calibration test procedure is
      necessary to validate the instrumentation; a few of the suggested calibration
      reactions are the enthalpies of solution associated with dissolving Tris in 0.1 M
      HCl or NaCl, KCl or propan-1-ol in water. In addition, there are a number of
      different methods available to determine enthalpies of solution from the
      experimental data provided by the calorimeter, for example, the Regnault
      Pfaundler's method, a graphical extrapolation based on the Dickinson method, or a
      manual integration-based method. Thus, the aim of the study was to investigate
      how each of these methods influences the values for the enthalpy of solution.
      Experiments were performed according to the method outlined by Hogan and Buckton
      [Int. J. Pharm. 207 (2000) 57] using KCl (samples of 50, 100 and 200 mg), Tris
      and sucrose as calibrants. For all three materials the manual integration method
      was found to be the most consistent with the KCl in water (sample mass of 200 mg)
      being the most precise. Thus, this method is recommended for the validation of
      solution calorimeters.

PMID- 14706249
TI  - Development of a perillyl alcohol topical cream formulation.
AB  - Perillyl alcohol (POH) is a relatively non-toxic agent that has been shown to be
      a promising anticancer monoterpene in preclinical models. Studies have indicated
      that topical application of POH may prove to be effective as a skin cancer
      chemoprevention therapy. The main aim of this study was to determine the
      influence of several factors on the stability of POH in solution and develop a
      topical formulation of POH. During preformulation, the influence of pH,
      temperature, ionic strength, and organic solvents, on the stability of POH was
      evaluated at four different temperatures: 4, 25, 37, and 48 degrees C. POH was
      found to degrade under acidic conditions with degradation following apparent
      first-order kinetics. A hydrophilic topical cream formulation of POH was
      developed and prepared for toxicology and clinical studies. A reverse phase
      gradient HPLC method was developed to quantitate POH in the complex formulation.
      Stability studies of the formulation and a placebo were performed and the
      formulation was found to be physically and chemically stable over a period of 1
      year at 4 and 25 degrees C.

PMID- 14706250
TI  - Evaluation of the vibratory feeder method for assessment of powder flow
      properties.
AB  - The flow properties of pharmaceutical powders and blends used in solid oral
      dosage forms are an important consideration during dosage form development. The
      vibratory feeder method, a flow measurement technique that quantifies avalanche
      flow, has been adapted for measurement of the flow properties of common
      pharmaceutical powders used in solid oral dosage forms. The flow properties of 17
      different powders were measured with the instrument, and the results are reported
      as a powder flow index (PFI). The PFI trends of the powders correlate well with
      flow properties reported in the literature. The flow properties of the powders
      were also measured with a commercially available avalanche instrument, the Aero
      Flow, and the results were reported as the mean time to avalanche (MTA). Since
      the two instruments analyze the avalanche by different algorithms, the results
      were compared with nonparametric statistical evaluation of ranked data, and they
      were found to be in excellent agreement. A recommended procedure for measurement
      of powder flow with the vibratory feeder is presented.

PMID- 14706251
TI  - Film coating as a method to enhance the preparation of tablets from
      dimenhydrinate crystals.
AB  - Crystals of dimenhydrinate as a model drug were used for crystal coating, a
      method that can be applied to increase the flowability of a material and
      facilitate the tablet making. An increase in particle size was observed during
      the film coating. The change in shape of the coated particles was also examined.
      Some physicochemical parameters changed during coating, e.g. the surface free
      energy parameters and the wetting of the samples. The amount of coating material
      (and therefore the coating time) influenced several parameters (the shape of the
      particles, the flow properties and surface free energy parameters,
      compressibility and compactibility). Several parameters of prepared tablet
      (porosity, breaking hardness) were examined. Accordingly, coating of the crystals
      can be performed in order to enhance the handling of a material with insufficient
      properties for tablet making.

PMID- 14706252
TI  - Simulation of roller compaction using a laboratory scale compaction simulator.
AB  - A method for simulation of the roller compaction process using a laboratory scale
      compaction simulator was developed. The simulation was evaluated using
      microcrystalline cellulose as model material and ribbon solid fraction and
      tensile strength as key ribbon properties. When compacted to the same solid
      fractions, real and simulated ribbons exhibited similar compression behavior and
      equivalent mechanical properties (tensile strengths). Thus, simulated and real
      ribbons are expected to result in equivalent granulations. Although the
      simulation cannot account for some roller compaction aspects (non-homogeneous
      ribbon density and material bypass) it enables prediction of the effects that
      critical parameters such as roll speed, pressure and radius have on the
      properties of ribbons using a fraction of material required by conventional
      roller compaction equipment. Furthermore, constant ribbon solid fraction and/or
      tensile strength may be utilized as scale up and transfer factors for the roller
      compaction process. The improved material efficiency and product transfer methods
      could enable formulation of tablet dosage forms earlier in drug product
      development.

PMID- 14706253
TI  - Preparation and physicochemical properties of niclosamide anhydrate and two
      monohydrates.
AB  - The intent of the study was to prepare and characterize three crystal forms of
      niclosamide namely the anhydrate and the two monohydrates and to investigate the
      moisture adsorption and desorption behavior of these crystal forms. The crystal
      forms were prepared by recrystallization and were characterized by differential
      scanning calorimetry, thermogravimetric analysis, isoperibol solution
      calorimetry, Karl Fischer titration, and X-ray powder diffractometry. Moisture
      adsorption by the anhydrate at increased relative humidities and two
      temperatures, 30 and 40 degrees C, was measured while the desorption from the
      monohydrates was determined at 45, 55, and 65 degrees C for monohydrate H(A) and
      75, 90, and 100 degrees C for monohydrate H(B). Thermal analysis and solution
      calorimetry showed that monohydrate H(B) is more stable than monohydrate H(A) and
      solubility measurements showed the solubility of the crystal forms decreased in
      the order: anhydrate>>monohydrate H(A)>monohydrate H(B). With an increase in
      temperature and relative humidity niclosamide anhydrate adsorbed moisture to form
      monohydrate H(A) by a random nucleation process. Dehydration of monohydrate H(A)
      at increased temperatures followed zero order kinetics and resulted in a change
      to the anhydrate. Monohydrate H(B) was transformed to the anhydrate at higher
      temperatures by a three-dimensional diffusion mechanism.

PMID- 14706254
TI  - Moisture sorption by cellulose powders of varying crystallinity.
AB  - Moisture in microcrystalline cellulose may cause stability problems for moisture
      sensitive drugs. The aim of this study was to investigate the influence of
      crystallinity and surface area on the uptake of moisture in cellulose powders.
      Powders of varying crystallinity were manufactured, and the uptake of moisture
      was investigated at different relative humidities. The structure of the cellulose
      powders was characterized by X-ray diffraction, BET surface area analysis, and
      scanning electron microscopy. Moisture uptake was directly related to the
      cellulose crystallinity and pore volume: Cellulose powders with higher
      crystallinity showed lower moisture uptake at relative humidities below 75%,
      while at higher humidities the moisture uptake could be associated with filling
      of the large pore volume of the cellulose powder of highest crystallinity. In
      conclusion, the structure of cellulose should be thoroughly considered when
      manufacturing low moisture grades of MCC.

PMID- 14706255
TI  - Effects of plasma irradiation on the wettability and dissolution of compacts of
      griseofulvin.
AB  - In this study, the use of plasma irradiation was investigated as a possible
      technique for increasing the dissolution rate of the poorly soluble drug
      griseofulvin. Plasma is a partially ionised gas consisting of ions, electrons and
      neutral species. Oxygen plasma was used to treat griseofulvin compacts as this
      would lead to the formation of oxygen containing functional groups on the surface
      of the compact thus increasing the wettability. Compacts containing 300 mg of the
      drug were prepared using a stainless steel punch and die assembly and plasma
      treated. The effect of the length and power of the plasma treatment upon the
      dissolution rate of griseofulvin was investigated. Dissolution experiments of
      griseofulvin were carried out using the paddle method using 0.1 M HCl and 0.1 M
      HCl with 2% sodium dodecyl sulphate (SDS) as the dissolution media. The
      wettability was assessed by contact angle measurements using the sessile drop
      technique with the contact angle being measured every second for a period of ten
      seconds using pure water (to European Pharmacopoeia standards). Plasma treated
      and untreated samples were also analysed by scanning electron microscopy.
      Although plasma treatment was found to increase the wettability of griseofulvin
      it was not found to increase the dissolution rate as the treatment caused surface
      fusion of the material.

PMID- 14706256
TI  - Transport of proteins and peptides across human cultured alveolar A549 cell
      monolayer.
AB  - An in vitro cultured monolayer system of alveolar epithelial cells was used as a
      model to investigate the transport pathway of the peptides and proteins, salmon
      calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant
      human growth hormone (rhGH), in pulmonary epithelium. Human lung adenocarcinoma
      A549 cells formed continuous monolayers when grown on the polycarbonate filters
      of Transwell plates. The transport of the peptides and proteins having MW of 3400
      22,000 Da was studied under different conditions. The results showed that the
      apparent permeability coefficients (P(app)) of these macromolecules across A549
      cell monolayers ranged from 2x10(-6) to 5x10(-6) cm s(-1) and exhibited a good
      inverse correlation with molecular weight. No concentration, direction, or
      temperature dependence was observed in the permeation of sCT, INS, and rHAV2.
      While the P(app) of rhGH in the BA direction (2.25x10(-6) cm s(-1)) was less than
      that in the AB direction at both concentrations (3.20x10(-6) and 3.29x10(-6) cm
      s(-1)). The P(app) values of rhGH were concentration and temperature independent
      in the AB direction. These findings suggest that the hydrophilic peptides and
      proteins used in this study, sCT, INS, rHAV2, and rhGH, appear to cross the A549
      cell monolayers via a paracellular pathway by a passive diffusion mechanism.

PMID- 14706257
TI  - Formulation and characterization of spray-dried powders containing nanoparticles
      for aerosol delivery to the lung.
AB  - Spray-drying is a common practice of powder preparation for a wide range of
      drugs. Spray-dried powders can be used to deliver particles to the lungs via a
      dry powder inhaler (DPI). The present study investigated the feasibility of
      developing a platform for aerosol delivery of nanoparticles. Lactose was used as
      the excipient and spray-dried with two different types of nanoparticles: gelatin
      and polybutylcyanoacrylate nanoparticles. Results showed that some carrier
      particles were hollow while others had a continuous matrix. Gelatin nanoparticles
      were incorporated throughout the matrix and sometimes accumulated at one end of
      the lactose. Polycyanoacrylate nanoparticles mostly clustered in different spots
      within the lactose carriers. The mean sizes of both nanoparticle types were
      characterized at two different times: before they were spray-dried and after they
      were redissolved from the spray-dried powders. Both nanoparticle types remained
      in the nano-range size after spray-drying. The mean nanoparticle sizes were
      increased by approximately 30% after spray-drying, though this increase was
      statistically significant only for the gelatin nanoparticles. Dispersion of the
      powder with an in-house passive dry powder inhaler and subsequent cascade
      impaction measurements showed that incorporation of the nanoparticles did not
      affect the fine particle fraction (FPF) or mass median aerodynamic diameter
      (MMAD) of the powders. FPF was approximately 40% while MMAD was 3.0+/-0.2 microm,
      indicating the present formulations yield aerosols of a suitable particle size
      for efficient lung delivery of nanoparticles. The present work demonstrates that
      nanoparticles can be delivered to the lungs via carrier particles that dissolve
      after coming in contact with the aqueous environment of the lung epithelium. This
      opens the way for new drug-targeting strategies using nanoparticles for pulmonary
      delivery of drugs and diagnostics.

PMID- 14706258
TI  - Intercalation of amino acids and peptides into Mg-Al layered double hydroxide by
      reconstruction method.
AB  - The intercalation of amino acids and some peptides into Mg-Al layered double
      hydroxide known as hydrotalcite was examined. Although the intercalation by ion
      exchange method was unsuccessful, all the amino acids except for Lys and Arg, and
      peptides examined could be intercalated into the layered double hydroxide by
      reconstruction method using Mg-Al oxide precursor. The uptake amounts of amino
      acids and peptides were 0.9-2.7 mmol per 1 g of LDH. Intercalation compounds were
      examined by using XRD and solid-state NMR. For Gly, Ala, Ser, Thr, Pro, Asn, Gln,
      Asp, Glu, and aspartame the intercalation accompanied the expansion of interlayer
      distance of the solid products, whereas the other amino acids and oligoglycine
      showed no expansion. The intercalation mechanism and release profile in K(2)CO(3)
      aqueous solution were also investigated. And the cointercalation of amino acids
      and peptides into Mg-Al LDH and easy release of amino acids from the LDH layer
      were found.

PMID- 14706260
TI  - Poly(epsilon-caprolactone) and Eudragit microparticles containing fludrocortisone
      acetate.
AB  - Substitutive hormonal therapies have to be administered for long periods. Thus,
      the development of sustained-release forms, as microparticle suspensions, is
      interesting in order to improve patient compliance by reducing dosing frequencies
      and side effects. The aim of this work was to compare different formulations of
      fludrocortisone microparticles for the treatment of mineralocorticoid
      insufficiency. The study was done with different polymers (poly(epsilon
      caprolactone), Eudragit RS and Eudragit RL) and different processes (O/W solvent
      evaporation methods and S/O/W evaporation methods). The use of a suspension of
      micronized drug in dichloromethane as dispersed phase (S/O/W method)
      significantly improved the process. Whereas low concentrations of FLU dissolved
      in the dispersed phase led to smooth-surface homogeneous microparticles and poor
      incorporation efficiency (5.8-7.3%); suspensions of FLU led to microparticles
      with numerous crystals on their surfaces (S/O/W microparticles) and high
      incorporation efficiency (about 79%). However, the best release profiles were
      obtained with microparticles prepared with 7.5 mg/ml of dichloromethane, near
      saturation. Moreover, the use of mixtures of poly(epsilon-caprolactone), Eudragit
      RS and RL did not improve the release profiles.

PMID- 14706259
TI  - Serum aminotransferase activity as a predictor of clearance of drugs metabolized
      by CYP isoforms in rats with acute hepatic failure induced by carbon
      tetrachloride.
AB  - The values of serum aminotransferase activity (AST) in untreated rats and rats
      with acute hepatic failure at 24h after an oral administration of CCl(4) (0.5
      ml/kg) were 85+/-9 IU/l and 4260+/-620 IU/l (mean+/-S.D., n=6), respectively. The
      values of total clearance (CL(tot)) after intravenous administration of caffeine,
      tolbutamide, chlorzoxazone or lidocaine (as probe drugs for various CYP isoforms)
      to CCl(4)-treated rats were decreased to about 1/8, 1/3, 1/3 or 1/2 compared with
      those in untreated rats. Good correlations were observed between mRNA expression
      and enzyme activity of CYP2C11, CYP2E1, CYP3A2 and CYP1A2 in livers of rats given
      various doses of CCl(4). There was also a good negative correlation between serum
      AST activity and hepatic enzyme activity of each CYP. The serum AST activities
      corresponding to a 50% decrease of CYP2C 11, CYP2E1, CYP3A2 and CYP1A2 activities
      were about 710, 780, 1030 and 1300 IU/l, respectively. In conclusion, when the
      serum AST value in CCl(4)-treated rats reached about 4000 IU/l, the hepatic CYP
      activities were one-tenth or less of the control, although the degree of decrease
      of the CL(tot) values varied markedly. Nevertheless, the AST value appears to be
      a promising candidate for an indicator to predict appropriate dose modification
      of drugs for patients with acute hepatic failure.

PMID- 14706261
TI  - Physicochemical properties and mechanism of drug release from ethyl cellulose
      matrix tablets prepared by direct compression and hot-melt extrusion.
AB  - The objective of this research project was to determine the physicochemical
      properties and investigate the drug release mechanism from ethyl cellulose (EC)
      matrix tablets prepared by either direct compression or hot-melt extrusion (HME)
      of binary mixtures of water soluble drug (guaifenesin) and the polymer. Ethyl
      cellulose was separated into "fine" or "coarse" particle size fractions
      corresponding to 325-80 and 80-30 mesh particles, respectively. Tablets
      containing 30% guaifenesin were prepared at 10, 30, or 50 kN compaction forces
      and extruded at processing temperatures of 80-90 and 90-110 degrees C. The drug
      dissolution and release kinetics were determined and the tablet pore
      characteristics, tortuosity, thermal properties and surface morphologies were
      studied using helium pycnometry, mercury porosimetry, differential scanning
      calorimetry and scanning electron microscopy. The tortuosity was measured
      directly by a novel technique that allows for the calculation of diffusion
      coefficients in three experiments. The Higuchi diffusion model, Percolation
      Theory and Polymer Free Volume Theory were applied to the dissolution data to
      explain the release properties of drug from the matrix systems. The release rate
      was shown to be dependent on the ethyl cellulose particle size, compaction force
      and extrusion temperature.

PMID- 14706262
TI  - Administration of an insulin powder to the lungs of cynomolgus monkeys using a
      Penn Century insufflator.
AB  - A powder formulation of live-attenuated measles vaccine is being developed for
      administration to the lungs. The safety and efficacy of the powder will be
      assessed by insufflation into cynomolgus monkeys. A Penn Century insufflator has
      been evaluated for powder dosing to the monkeys using an insulin formulation
      having similar physicochemical characteristics to the vaccine powder. Insulin
      pharmacokinetics were compared following dosing by powder insufflation, solution
      instillation into the trachea and subcutaneous injection. The insulin dosed to
      the lungs and trachea was more rapidly absorbed than that administered
      subcutaneously. Insulin bioavailability was greater from the inhaled powder than
      from the instilled solution. The findings confirm that the Penn Century device is
      suitable for vaccine powder dosing to the deep lung.

PMID- 14706263
TI  - Problems with the decontamination of dental handpieces and other intra-oral
      dental equipment in hospitals.
AB  - Dental departments within district general hospitals contain items of equipment
      that require decontamination between patients. Some of these items are complex
      and expensive, and in busy clinics, may be required in large numbers if a sterile
      services department (SSD) were to be used. This may result in local manual
      cleaning of these instruments and sterilization in non-vacuum downward
      displacement autoclaves within dental departments, despite some items having
      narrow lumens, deep recesses and cavities, which will not adequately sterilize
      these instruments. Infection control teams should be aware of these difficulties
      particularly when arranging satisfactory infection control and decontamination
      procedures in hospital dental departments.

PMID- 14706264
TI  - Making a meal of MRSA-the role of biosurgery in hospital-acquired infection.
AB  - Fly larvae have been used by many different cultures for treating wounds
      throughout history. Recently, their therapeutic actions have been scientifically
      defined. This article reviews the history of biosurgery and the most recent
      research, which demonstrates the therapeutic action of larvae and particularly
      their anti-MRSA properties.

PMID- 14706265
TI  - How do we assess hospital cleaning? A proposal for microbiological standards for
      surface hygiene in hospitals.
AB  - Increasing numbers of hospital-acquired infections have generated much attention
      over the last decade. The public has linked the so-called 'superbugs' with their
      experience of dirty hospitals, but the precise role of cleaning in the control of
      these organisms in unknown. Hence the importance of a clean environment is likely
      to remain speculative unless it becomes an evidence-based science. This proposal
      is a call for bacteriological standards with which to assess clinical surface
      hygiene in hospitals, based on those used by the food industry. The first
      standard concerns any finding of a specific 'indicator' organism, the presence of
      which suggests a requirement for increased cleaning. Indicators would include
      Staphylococcus aureus, including methicillin-resistant S. aureus, Clostridium
      difficile, vancomycin-resistant enterococci and various Gram-negative bacilli.
      The second standard concerns a quantitative aerobic colony count of <5 cfu/cm(2)
      on frequent hand touch surfaces in hospitals. The principle relates to modern
      risk management systems such as HACCP, and reflects the fact that pathogens of
      concern are widespread. Further work is required to evaluate and refine these
      standards and define the infection risk from the hospital environment.

PMID- 14706266
TI  - Ten years phage-typing of Belgian clinical methicillin-resistant Staphylococcus
      aureus isolates (1992-2001).
AB  - Gradual changes have been observed in the phage-types of methicillin-resistant
      Staphylococcus aureus (MRSA) isolates from Belgian hospitals. A total of 6551
      isolates, collected in 93 Belgian hospitals over 10 years (1992-2001), was
      examined. A decreasing incidence of the main early Belgian epidemic phage-types
      ([A], [B], [H]*, Jo*) was observed. Since 1997 and 2000, a new series of phage
      types ([Hv]*, [J]*, [O]*), which were likely related to the previous group [H]*,
      have been noted. The general trends were confirmed in two particular hospitals.
      Local epidemic and/or endemic phage-types were also encountered.

PMID- 14706267
TI  - Methicillin-resistant Staphylococcus aureus bacteraemia in Western Australian
      teaching hospitals, 1997-1999: risk factors, outcomes and implications for
      management.
AB  - The aim of this study was to document the evolution of methicillin-resistant
      Staphylococcus aureus (MRSA) bacteraemia at teaching hospitals in Perth, Western
      Australia (WA), and determine the risk factors and outcomes of the disease. We
      performed a retrospective case series analysis of all laboratory-confirmed
      episodes of S. aureus bacteraemia at Perth teaching hospitals between 1 July 1997
      and 30 June 1999 by linking laboratory data with hospitalization data from the
      state's Hospital Morbidity Data System. Episodes of S. aureus bacteraemia were
      stratified according to methicillin susceptibility and the relationship between
      methicillin resistance and key factors or outcomes was determined. Almost 11% of
      episodes of S. aureus bacteraemia (55/509) were caused by MRSA. On age-adjusted
      multivariate analysis, Aboriginality (RR 6.71, 95% CI 3.20-14.10, P<0.001),
      geriatric unit admission (RR 5.74, 95% CI 2.01-16.37, P=0.001), female sex (RR
      1.88, 95% CI 1.03-3.42, P=0.04) and healthcare-associated disease (RR 1.93, 95%
      CI 1.01-3.70, P=0.05) were independently associated with MRSA bacteraemia.
      Outcomes among those with MRSA bacteraemia included death in 15 patients and re
      admission for an MRSA-related complication in five. Empirical use of vancomycin
      needs consideration in at-risk patients in whom Gram-positive bacteraemia is
      suspected clinically, with prompt review of therapy once antibiotic
      susceptibility results are known. The rates of re-admission after discharge for
      MRSA bacteraemia could be used as a clinical indicator to monitor the quality of
      care in hospitals.

PMID- 14706268
TI  - A nosocomial outbreak of Serratia marcescens producing inducible Amp C-type beta
      lactamase enzyme and carrying antimicrobial resistance genes within a class 1
      integron.
AB  - We investigated an outbreak of Serratia marcescens in the adult intensive care
      unit of the University Hospital of Napoli. The outbreak involved 13 cases of
      infection by S. marcescens over a nine-month period and was caused by a single
      pulsed-field gel electrophoresis clone. The epidemic strain was multiply
      antibiotic resistant, producing an inducible Amp C-type beta-lactamase enzyme and
      carrying the trimethoprim-resistance gene and the adenyltransferase gene, which
      confers resistance to streptomycin and spectinomycin, within a class 1 integron.
      Antimicrobial therapy with beta-lactams was associated with S. marcescens
      acquisition in the intensive care unit.

PMID- 14706269
TI  - Plasma cleaning of dental instruments.
AB  - The theoretical risk of prion transmission via surgical instruments is of current
      public and professional concern. These concerns are further heightened by reports
      of the strong surface affinity of the prion protein, and that the removal of
      organic material by conventional sterilization is often inadequate. Recent
      reports of contamination on sterilized endodontic files are of particular
      relevance given the close contact that these instruments may make with peripheral
      nerve tissue. In this paper, we report the effective use of a commercial gas
      plasma etcher in the cleaning of endodontic files. A representative sample of
      cleaned, sterilized, files was screened, using scanning electron microscopy and
      energy-dispersive X-ray analysis, to determine the level of contamination before
      plasma cleaning. The files were then exposed for a short-term to a low-pressure
      oxygen-argon plasma, before being re-examined. In all cases, the amount of
      organic material (in particular that which may have comprised protein) was
      reduced to a level below the detection limit of the instrument. This work
      suggests that plasma cleaning offers a safe and effective method for
      decontamination of dental instruments, thus reducing the risk of iatrogenic
      transmission of disease during dental procedures. Furthermore, whilst this study
      focuses on dental files, the findings indicate that the method may be readily
      extended to the decontamination of general surgical instruments.

PMID- 14706270
TI  - Comparison of the collecting efficiency of microbiological air samplers.
AB  - It is important to evaluate the prevention of nosocomial infections caused by
      airborne micro-organisms in healthcare facilities. For that purpose, the use of
      an air sampler is required. A comparison of the collecting efficiency of air
      samplers has not been studied so far using a single culture medium. Use of the
      same culture medium is necessary because of the variation of the cultivation
      efficiency with different culture media. In this study a statistically
      significant difference in collecting efficiency among air samplers was observed
      in case of SCDA (soybean casein digest agar) culture medium, but not SCDALP
      (soybean casein digest agar lecithin polysorbate) culture medium. In addition, a
      statistically significant difference of the cultivation efficiency was observed
      between SCDA and SCDALP culture media (P<0.05). These results suggest that any
      air sampler can be used with SCDALP culture medium.

PMID- 14706271
TI  - Inactivation of feline calicivirus, a surrogate of norovirus (formerly Norwalk
      like viruses), by different types of alcohol in vitro and in vivo.
AB  - Hand disinfection is an important measure to prevent transmission of norovirus
      (formerly called Norwalk-like viruses) from hands or environmental surfaces to
      other objects. Therefore, three types of alcohol (ethanol, 1- and 2-propanol)
      were examined for their virus-inactivating properties against feline calicivirus
      (FCV) as a surrogate for norovirus. Tests were performed as quantitative
      suspension assays or as in vivo experiments with artificially contaminated
      fingertips. The in vitro experiments showed that 1-propanol was more effective
      than ethanol and 2-propanol for the inactivation of FCV: in tests with the 50 and
      70% solutions of the different alcohols, a 10(4)-fold reduction was observed with
      1-propanol after 30 s, whereas the other alcohols were effective only after 3 min
      contact time. The greatest efficacy did not occur at the highest concentrations
      (80%). The following concentrations (extrapolated data) showed the greatest virus
      inactivating properties in the suspension test: ethanol 67%, 2-propanol 58%
      (exposure times of 1 min) and 1-propanol 60% (exposure time of 30 s). The results
      from fingertips experiments with 70 and 90% solutions and an application time of
      30 s confirmed these findings: the 70% alcoholic solutions were more effective
      than the 90% solutions. In contrast to the suspension tests, 70% ethanol showed
      the greatest efficacy in vivo with a log(10) reduction factor (RF) of 3.78
      compared with 70% 1-propanol (RF 3.58), 70% 2-propanol (RF 2.15) and hard water
      (RF 1.23). Ethanol and 1-propanol-based solutions with a high alcohol content
      thus appear most effective.

PMID- 14706272
TI  - Performance feedback of hand hygiene, using alcohol gel as the skin
      decontaminant, reduces the number of inpatients newly affected by MRSA and
      antibiotic costs.
AB  - In March 2000 the Plastic Surgery Unit of our 600-bedded district general
      hospital agreed to be the pilot ward for the introduction of a new standard of
      hand hygiene, emphasizing the use of alcohol gel on socially clean hands between
      clinical contact with patients. Hand hygiene practice of healthcare workers
      (HCWs) was observed using Formic forms. The data from completed forms were
      scanned into an Excel database, and results fed back to HCWs in graphical form.
      The case notes of patients newly affected by methicillin-resistant Staphylococcus
      aureus (MRSA), likely to have been acquired as inpatients, were reviewed for one
      year before and after this performance feedback of hand hygiene. The cost of
      teicoplanin use (for MRSA infections) was also determined for the two periods.
      There was a significant reduction in the number of patients newly affected by
      MRSA (P<0.05), and in the use of teicoplanin, suggesting that performance
      feedback of hand hygiene reduces nosocomial MRSA infection rates and antibiotic
      use.

PMID- 14706273
TI  - Nosocomial outbreak of norovirus gastroenteritis and investigation of ABO histo
      blood group type in infected staff and patients.
AB  - The blood groups were analysed of staff and patients (N=45) infected during two
      nosocomial outbreaks of norovirus gastroenteritis at a German University
      hospital. Persons with O phenotype were significantly less affected than was
      expected from the normal distribution of blood group types in Southwest Germany
      (OR 2.45; 95% CI 1.22-4.95; P=0.01).

PMID- 14706274
TI  - Quality of local guidelines for surgical antimicrobial prophylaxis.
AB  - Surgical antimicrobial prophylaxis (AMP) is an effective measure to prevent
      surgical site infections. To determine the quality and availability of local
      guidelines for AMP, a survey was conducted in the public hospitals of a Northern
      Italian region. The guidelines for "Antimicrobial Prophylaxis in Surgery" by the
      Scottish Intercollegiate Guidelines Network (SIGN) were used as a standard by
      which the quality of the local guidelines was compared. The coverage of surgical
      specialities by local AMP guidelines was 93.1% for hospitals where guidelines had
      been developed at hospital level and 47% for hospitals where guidelines had been
      developed by individual surgical departments. Local guidelines recommended AMP
      for most surgical procedures (96%), including procedures with evidence against
      the use of antimicrobial prophylaxis (87% of these procedures). Only 8% of all
      procedure-specific guidelines (PSG) recommended an incorrect timing of AMP (not
      administering AMP at the induction of anaesthesia), while 41% recommended an
      incorrect duration (additional antimicrobial doses after completion of the
      surgical operation). This survey showed that having written protocols at local
      level does not necessarily mean they comply with available scientific evidence.
      Thus, the quality of local guidelines needs to be improved.

PMID- 14706275
TI  - SARS and masks.

PMID- 14706276
TI  - Relation between bed occupancy and the incidence of MRSA infection.

PMID- 14706277
TI  - Lidocaine/prilocaine cream (EMLA) has an antibacterial effect in vitro.

PMID- 14706278
TI  - Polyclonal outbreaks-more common than you expect.

PMID- 14706279
TI  - Ralstonia pickettii outbreak associated with contaminated distilled water used
      for respiratory care in a paediatric intensive care unit.

PMID- 14706280
TI  - Detergent versus hypochlorite cleaning and Clostridium difficile infection.

PMID- 14706281
TI  - Variations in aseptic techniques during preparation and administration of
      intravenous drugs-an observation-based study in the UK and in Germany.

PMID- 14706282
TI  - Missing data and participation or non-participation in a surgical-site infection
      surveillance network.

PMID- 14706283
TI  - Activation of the Drosophila TRP and TRPL channels requires both Ca2+ and protein
      dephosphorylation.
AB  - The Transient Receptor Potential (TRP) proteins constitute a large and diverse
      family of channel proteins, which is conserved through evolution. TRP channel
      proteins have critical functions in many tissues and cell types, but their gating
      mechanism is an enigma. In the present study patch-clamp whole-cell recordings
      was applied to measure the TRP- and TRP-like (TRPL)-dependent currents in
      isolated Drosophila ommatidia. Also, voltage responses to light and to metabolic
      stress were recorded from the eye in vivo. We report new insight into the gating
      of the Drosophila light-sensitive TRP and TRPL channels, by which both Ca2+ and
      protein dephosphorylation are required for channel activation. ATP depletion or
      inhibition of protein kinase C activated the TRP channels, while photo-release of
      caged ATP or application of phorbol ester antagonized channels openings in the
      dark. Furthermore, Mg(2+)-dependent stable phosphorylation event by ATPgammaS or
      protein phosphatase inhibition by calyculin A abolished activation of the TRP and
      TRPL channels. While a high reduction of cellular Ca2+ abolished channel
      activation, subsequent application of Ca2+ combined with ATP depletion induced a
      robust dark current that was reminiscent of light responses. The results suggest
      that the combined action of Ca2+ and protein dephosphorylation activate the TRP
      and TRPL channels, while protein phosphorylation by PKC antagonized channels
      openings.

PMID- 14706284
TI  - A role for hTRPC1 and lipid raft domains in store-mediated calcium entry in human
      platelets.
AB  - We have previously suggested that store-mediated Ca2+ entry (SMCE) in human
      platelets may be activated by a secretion-like coupling model, involving de novo
      coupling of the type II inositol 1,4,5-trisphosphate receptor (IP(3)RII) to the
      putative Ca2+ entry channel, hTRPC1. In other cells, hTRPC1 has been reported to
      be associated with cholesterol-rich lipid raft domains (LRDs) in the plasma
      membrane. Here we have shown that hTRPC1 is largely associated with detergent
      resistant platelet membranes, from which it is partially released when the cells
      are depleted of cholesterol by treatment with methyl-beta-cyclodextrin (MBCD).
      MBCD treatment inhibited thapsigargin (TG)-evoked SMCE in a concentration
      dependent manner, reducing it to 38.1+/-4.1% at a concentration of 10mM.
      Similarly, the Ca2+ entry evoked by thrombin (1unit/ml) was reduced to 48.2+/
      4.5% of control following MBCD (10mM) treatment. Thrombin- and TG-evoked coupling
      between IP(3)RII and hTRPC1 was also reduced following cholesterol depletion.
      These results suggest that hTRPC1 is associated with LRDs in human platelets and
      that these domains are important for its participation in SMCE.

PMID- 14706285
TI  - Inositol trisphosphate producing agonists do not mobilize the thapsigargin
      insensitive part of the endoplasmic-reticulum and Golgi Ca2+ store.
AB  - Non-mitochondrial intracellular Ca2+ stores contain both thapsigargin-sensitive
      sarco(endo)plasmic-reticulum Ca2+-ATPases (SERCA) and thapsigargin-insensitive
      secretory-pathway Ca2+-ATPases (SPCA1). We now have studied the Ca2+-release
      properties of the compartments associated with these pumps in intact, i.e. non
      permeabilized, cells of different origin (HeLa, keratinocytes, 16HBE14o-, COS-1,
      A7r5) and with different approaches (45Ca2+ fluxes, Ca2+ imaging and measurements
      of the free luminal [Ca2+] in the endoplasmic-reticulum and the Golgi apparatus
      using targeted aequorin). Application of an extracellular agonist in the absence
      of thapsigargin induced in all cells a Ca2+ release from both the endoplasmic
      reticulum and the Golgi apparatus. The agonists were not able to release Ca2+ in
      the presence of 10 microM thapsigargin, except in COS-1 cells overexpressing
      SPCA1, where this pump not only appeared in the Golgi compartment but also
      overflowed into the agonist-sensitive part of the endoplasmic-reticulum. We
      conclude that the subcompartments of the endoplasmic-reticulum and of the Golgi
      complex that endogenously express SPCA1 are insensitive to agonist stimulation.

PMID- 14706286
TI  - Calcium response after stimulation by substance P of U373 MG cells: inhibition of
      store-operated calcium entry by protein kinase C.
AB  - In this paper we investigate the Ca2+ response after Substance P (SP) stimulation
      of U373 MG cells. SP is a tachykinin and physiologically acts as a
      neurotransmitter and neuromodulator in the nervous system, but pathologically
      triggers malignant glial cells, such as U373 MG, to release cytokines and
      increase proliferation rate. In this paper we show that SP increases the
      proliferation rate of U373 MG cells and the intracellular Ca2+ concentration by
      mobilizing Ca2+ only from thapsigargin-sensitive stores. In fact, Ca2+ entry
      through store-operated calcium entry (SOCE) channels, which was observed after
      thapsigargin treatment, was not detected after stimulation by SP. The inhibition
      of SOCE after SP stimulation must be mediated by protein kinase C (PKC), because
      it was not observed in the presence of calphostin C (an inhibitor of PKC).
      Moreover, stimulation by SP-induced membrane potential hyperpolarization. Our
      results are consistent with the following sequence of events: (i) SP interacts
      with NK(1) receptors; (ii) fast homologous receptor desensitization occurs; (iii)
      reuptake by endoplasmic reticulum Ca(2+)-ATPase quantitatively overwhelms the
      extrusion by plasma membrane Ca2+-ATPase. These results have two important
      consequences. In U373 MG cells the SOCE does not contribute to the Ca2+ response
      after SP, and is not necessarily involved in promoting cell proliferation.

PMID- 14706287
TI  - Gene silencing of selected calcium-signalling molecules in a Drosophila cell line
      using double-stranded RNA interference.
AB  - Using the Drosophila melanogaster S2 cell line, stably expressing a cloned
      muscarinic acetylcholine receptor (AChR), DM1, we have applied gene silencing by
      double-stranded RNA interference (RNAi) to knock down gene products involved in
      DM1-mediated calcium signalling. We have shown that RNAi knock down of either the
      inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P(3)R), or the SERCA calcium
      pump in the S2-DM1 cells blocks the increase in intracellular calcium
      concentration ([Ca(2+)](i)) resulting from activation of the DM1 receptor by 100
      microM carbamylcholine (CCh). When RNAi designed to knock down the ryanodine
      receptor (RyR) was tested, there was no change in the calcium increase detected
      in response to CCh, consistent with a failure to detect RyRs in S2-DM1 cells
      using RT-PCR. A combination of RNAi and calcium imaging has provided a direct
      demonstration of key roles for the Ins(1,4,5)P(3)R and the SERCA pump in the
      response to DM1 receptor activation.Thus, we show that silencing of individual
      genes by RNAi in a well characterised Drosophila S2 cell line offers experimental
      opportunities for cell-signalling studies. Future investigations with RNAi
      libraries taking full advantage of the wealth of new information available from
      sequencing the Drosophila genome, may help identify novel components of cell
      signalling pathways and functionally linked gene products.

PMID- 14706288
TI  - Decreasing motion artifacts in calcium-dependent fluorescence transients from the
      perfused mouse heart using frequency filtering.
AB  - A strategy has been developed for the removal of motion artifact and noise in
      calcium-dependent fluorescence transients from the perfused mouse heart using
      frequency filtering. An analytical model indicates that the spectral removal of
      motion artifacts is independent of the phase shift of the motion waveform in the
      frequency domain, and thus to the time shift (or delay) of motion in the time
      domain. This is based on the "shift theorem" of Fourier analysis, which avoids
      erroneous correction of motion artifact when using the motion signal obtained
      using reflectance from the heart. Several major steps are adopted to implement
      this model for elimination of motion as well as detection noise from the
      fluorescence transient signals from the calcium-sensitive probe Rhod-2. These
      include (1) extracting the fluorescence calcium transient signal from the raw
      data by using power spectrum density (PSD) in the frequency domain by subtracting
      the motion recorded using the reflectance of excitation light, (2) digitally
      filtering out the random noise using multiple bandpass filters centralized at
      harmonic frequencies of the transients, and (3) extracting high frequency noise
      with a Gaussian Kernel filter method. The processed signal of transients acquired
      with excessive motion artifact is comparable to transients acquired with minimal
      motion obtained by immobilizing the heart against the detection window,
      demonstrating the usefulness of this technique.

PMID- 14706289
TI  - Long-lasting alterations in neuronal calcium homeostasis in an in vitro model of
      stroke-induced epilepsy.
AB  - Altered calcium homeostatic mechanisms have been implicated in the development of
      acquired epilepsy in numerous models. Stroke is one of the leading brain injuries
      that cause acquired epilepsy, yet little is known concerning the molecular
      mechanisms underlying stroke-induced epileptogenesis. Recently an in vitro model
      of stroke-induced epilepsy was developed and characterized as a powerful tool to
      study the pathophysiology of injury and stroke-induced epileptogenesis. Using
      this glutamate injury-induced epileptogenesis model, we have investigated the
      role of altered calcium homeostatic mechanisms in the development and maintenance
      of stroke-induced epilepsy. Epileptic neurons manifested elevated intracellular
      calcium levels compared to control neurons independent of neuronal activity and
      seizure discharge for the remainder of the life of the neurons in culture. In
      addition, epileptic neurons were found to have alterations in the ability to
      reduce intracellular calcium levels following a calcium load. These long-term
      epileptic changes in calcium homeostasis were dependent on calcium during the
      initial glutamate injury. The data demonstrate that significant alterations in
      calcium homeostatic mechanisms occur in association with stroke-induced epilepsy
      and suggest that these changes may play a role in both the induction and
      maintenance of the epileptic phenotype in this model.

PMID- 14706290
TI  - The calmodulin binding region of the skeletal ryanodine receptor acts as a self
      modulatory domain.
AB  - A synthetic peptide (CaMBP) matching amino acids 3614-3643 of the skeletal
      ryanodine receptor (RyR1) binds to both Ca2+-free calmodulin (CaM) and Ca2+-bound
      CaM with nanomolar affinity [J. Biol. Chem. 276 (2001) 2069]. We report here that
      CaMBP increases [3H]ryanodine binding to RyR1 in a dose- and Ca2+-dependent
      manner; it also induces Ca2+ release from SR vesicles, and increases open
      probability (P(o)) of single RyR channels reconstituted in planar lipid bilayers.
      Further, CaMBP removes CaM associated with SR vesicles and increases
      [3H]ryanodine binding to purified RyR1, suggesting that its mechanism of action
      is two-fold: it removes endogenous inhibitors and also interacts directly with
      complementary regions in RyR1. Remarkably, the N-terminus of CaMBP activates RyRs
      while the C-terminus of CaMBP inhibits RyR activity, suggesting the presence of
      two discrete functional subdomains within this region. A ryr1 mutant lacking this
      region, RyR1-Delta3614-3643, was constructed and expressed in dyspedic myoblasts
      (RyR1-knockout). The depolarization-, caffeine- and 4-chloro-m-cresol (4-CmC)
      induced Ca2+ transients in these cells were dramatically reduced compared with
      cells expressing wild type RyR1. Deletion of the 3614-3643 region also resulted
      in profound changes in unitary conductance and channel gating. We thus propose
      that the RyR1 3614-3643 region acts not only as the CaM binding site, but also as
      an important modulatory domain for RyR1 function.

PMID- 14706291
TI  - Endoscopy: a minimally invasive procedure for diagnosis and treatment of diseases
      of the salivary glands. Six years of practical experience.
AB  - During a 6-year period we did a total of 72 videoendoscopies of the salivary
      glands and their associated ductal systems. This minimally invasive procedure is
      associated with little morbidity and discomfort. The main indication was
      sialolithiasis of the submandibular and parotid glands. Sialoendoscopy was used
      not only for diagnosis of radiolucent calculi but also for simultaneous removal
      of calculi. Sialoendoscopy was also of benefit in the diagnosis and treatment of
      other diseases of the salivary glands. Even patients with chronic sialadenitis
      could be helped with endoscopic dilatation of the causative sialostenosis,
      thereby enabling us to conserve the gland.

PMID- 14706292
TI  - Use of hand-held laser scanning in the assessment of facial swelling: a
      preliminary study.
AB  - A new generation lightweight, hand-held, laser surface scanner (FastSCAN) was
      validated and clinically evaluated for the assessment of postoperative facial
      swelling. The potential sources of error-scanner error, registration error, and
      repositioning and movement error were established for laser scans of a mannequin
      head and seven volunteers. For the mannequin head the mean (S.D.) volume of the
      simulated swelling was 12.5 (0.5) cm3. The measurement error was therefore about
      4%, and reflected the error in scanned data and in surface registration. Among
      the volunteers, repositioning of the head introduced additional errors of up to
      7.6 cm3 (mean 1.8 cm3), illustrating the additional influence of variable
      positions. We then scanned 20 patients (9 women and 11 men, age range 18-26)
      before and 2 days after, third molar removal. The external, facial soft tissue
      volume changes were calculated for both left and right sides (range 0.2-64.3
      cm3). The main source of inaccuracy was again variability of position. Despite
      this, the FastSCAN proved to be a simple, accurate, and non-invasive method of
      measuring postoperative changes in volume in the external, soft tissues of the
      face. Minimising variability in position by using more precise positioning
      techniques will increase the accuracy of this technique and is a focus for future
      work.

PMID- 14706293
TI  - Attitudes of consultants to drinking alcohol on call.
AB  - 198 consultant surgeons were asked about their drinking habits and their attitude
      to drinking alcohol whilst on call. Some of the answers raise issues which cause
      concern. It may be appropriate to consider a similar questionnaire to a wider
      professional group.

PMID- 14706294
TI  - Use of dental panoramic tomographs to predict the relation between mandibular
      third molar teeth and the inferior alveolar nerve. Radiological and surgical
      findings, and clinical outcome.
AB  - OBJECTIVES: To compare preoperative radiological observations from dental
      panoramic tomographs (DPT), with surgical findings at removal of third molars
      with respect to the inferior alveolar nerve. STUDY DESIGN: One surgeon viewed the
      radiographs of 219 patients and recorded the radiological observations of the
      mandibular third molar tooth and the inferior alveolar nerve. The same surgeon
      removed the teeth and made detailed records of morphology of the root and its
      relation to the inferior alveolar nerve. Patients were reviewed postoperatively.
      RESULTS: A total of 300 teeth were removed and the neurovascular bundle was
      directly observed the root was grooved, or roots apices were deflected by the
      bundle in 35 (12%) cases. Postoperatively no patient had altered labial
      sensation. CONCLUSION: There was an intimate relation between the mandibular
      third molar tooth and the inferior alveolar nerve in 12 (51%) cases when
      darkening of the root was observed, and in only 11 (11%) cases when interruption
      of the radiopaque outline of the inferior alveolar neurovascular bundle was
      observed.

PMID- 14706296
TI  - Lymphatic malformation of the parapharyngeal space.
AB  - Lymphatic malformations are rare benign congenital lesions. A 28-month-old girl
      presented with a parapharyngeal lymphatic malformation. A cystic lesion had been
      diagnosed at 18 weeks' gestation by ultrasonography and she had been followed up
      conservatively until her referral to our department. We used a transcervical
      approach to excise the parapharyngeal lesion and 1 year later, there was no sign
      of recurrence.

PMID- 14706295
TI  - Diagnosis of intra-oral MALT lymphoma using seminested polymerase chain reaction.
AB  - Diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma based on
      histological examination alone is difficult. We report three patients with
      histologically suspected MALT lymphoma who developed lymphoproliferative lesions
      of the sublingual gland. Seminested polymerase chain reaction (PCR) analysis
      applied to formalin-fixed and paraffin-embedded specimens showed clonal
      rearrangement of immunoglobulin heavy chain genes in two patients and a
      polyclonal characteristic in one. The clinical findings and Southern blot
      analysis confirmed the accuracy of the diagnosis. The molecular method described
      can be applied routinely to processed specimens to obtain helpful information for
      the diagnosis of low-grade malignancies of lymphoproliferative disorders, such as
      MALT lymphoma.

PMID- 14706297
TI  - Radial free flaps using loupe magnification: audit of 97 cases of orofacial
      reconstruction.
AB  - We present a retrospective audit of radial fasciocutaneous vascularised free
      flaps performed over a decade. These have all been done with binocular loupe
      magnification, allowing comparison of free flap success with conventional
      microscope vessel anastomosis. The results are similar to other reported series.

PMID- 14706298
TI  - Skin necrosis of a pectoralis major myocutaneous flap, caused by methicillin
      resistant Staphylococcus aureus.
AB  - A case of MRSA-induced skin necrosis of part of a pectoralis muscle flap is
      described. It highlights the importance of recognising potential MRSA infection
      following surgery and treating it early and aggressively.

PMID- 14706299
TI  - Diagnosis and management of cervical teratomas.
AB  - We present three cases of cervical teratoma, two of which were detected
      prenatally by ultrasound. The two cases diagnosed prenatally showed rapid early
      growth, which indicated the aggressive nature of the tumour and assisted the
      parents' decision to terminate the pregnancy. The third case was undiagnosed
      prenatally and the child was born after a normal pregnancy and uncomplicated
      vaginal delivery. She recovered well after excision of the teratoma.

PMID- 14706300
TI  - Synchronous oral and gastric carcinoma. An incidental finding on Percutaneous
      Endoscopic Gastrostomy insertion.
AB  - Synchronous oral and gastric carcinoma in the western world is rare. We report a
      case of synchronous oral squamous cell carcinoma (SCC) and gastric adenocarcinoma
      which was found as an incidental finding during placement of a Percutaneous
      Endoscopic Gastrostomy (PEG) before resection of the oral tumour.

PMID- 14706301
TI  - Fin-edge osteotome for submucous palatal osteotomy.
AB  - We describe here a new osteotome for submucous palatal osteotomy. It enables safe
      sectioning of the palatal suture in the submucosal plane for rapid, surgically
      assisted maxillary expansion, using the approach from the piriform aperture.

PMID- 14706302
TI  - Pigmented villonodular synovitis of the temporomandibular joint: differential
      diagnosis and case report.
AB  - Pigmented villonodular synovitis of the temporomandibular joint (TMJ) is rare. We
      present a patient in whom the lesion had invaded the infratemporal fossa and
      destroyed the mandibular condyle.

PMID- 14706303
TI  - Subdural empyema and herpes zoster syndrome (Hunt syndrome) complicating removal
      of third molars.
AB  - We report a case of subdural empyema and herpes zoster syndrome (Hunt syndrome)
      complicating routine removal of third molars. Subdural empyema is an extremely
      rare but life-threatening complication of dental sepsis arising spontaneously or
      after dental surgery. The clinician should be familiar with its presentation and
      have a high index of suspicion, because late recognition and delay in its
      treatment can increase the associated morbidity and mortality. Surgical
      procedures and in particular maxillofacial surgery have also been known to
      trigger varicella zoster reactivation resulting in Hunt syndrome. Some patients
      develop the characteristic rash several days after the onset of facial weakness,
      so that Hunt syndrome may initially be misdiagnosed as Bell's palsy. We highlight
      the difficulties in diagnosing Hunt syndrome and argue the case for early
      treatment of all patients with Hunt syndrome and Bell's palsy with a combination
      of systemic steroids and antiviral drugs.

PMID- 14706304
TI  - Migration of gutta-percha point from a root canal into the ethmoid sinus.
AB  - There have been reports on the migration of teeth or implants into the maxillary
      sinus, but we know of no report on the migration of a gutta-percha point that had
      been used to fill a root canal into the ethmoid sinus. We report such a case
      which presumably migrated through the maxillary sinus.

PMID- 14706305
TI  - Closed treatment of condylar fractures by intermaxillary fixation with
      thermoforming plates.
AB  - We report a new intermaxillary fixation (IMF) method for condylar fractures using
      a thermoforming plate. Fifteen cases of condylar fracture were selected and
      thermoforming plates were applied. The patient's recover was uneventful in all 15
      cases, and the period of IMF ranged from 7 to 17 days, (mean 12) for the
      following 7 days IMF was used only at night together with functional jaw training
      during the day. The outcome was good. IMF using a thermoforming plate may be a
      useful technique for selected condylar fractures.

PMID- 14706306
TI  - Orientation of histopathology specimens.
AB  - We present a simple way of orientating large specimens being sent to the
      laboratory for histopathological examination by supplementing the pinning of the
      specimen on a cork board with Polaroid photographs of the specimen and numbered
      tags.

PMID- 14706307
TI  - A multidisciplinary approach to recurrent cervicothoracic cystic hygroma in an
      adult.
AB  - Cystic hygroma is a benign congenital lymphatic malformation affecting mainly the
      head and neck region in children. Although mediastinal or multiorgan
      lymphangiomatosis is rare, it can present at any age. We report an unusual case
      of recurrent bilateral cystic hygroma in an adult affecting both neck and
      mediastinum. When the extensive lesion became symptomatic, a multidisciplinary
      approach was necessary to remove the expanding mass to achieve the optimal
      functional and cosmetic outcome.

PMID- 14706308
TI  - Cervical Castleman disease in children.
AB  - We report a new case of cervical Castleman disease (hyaline vascular type) in a 6
      year-old child. The mass was shown on computed tomography and magnetic resonance
      angiography (MRA) to be compressing the bifurcation of the right common carotid
      artery. At operation four masses were found, which were tightly adherent to both
      the artery and the right jugular vein. These were removed by blunt dissection and
      there were no signs of recurrence after 6 months. This is a rare tumour (we know
      of only 24 other reports), which is usually asymptomatic, and of uncertain
      prognosis.

PMID- 14706309
TI  - Reconstruction of a congenital midpalatal hairy polyp.
AB  - Hairy polyps (dermoids or oronasopharyngeal teratomas) are a type of congenital
      tumour that contain elements of bigerminal origin (ectoderm and mesoderm). We
      describe a baby who presented with a hairy polyp of the hard palate protruding
      from the mouth. This was not causing respiratory distress but she had feeding
      difficulties. She was successfully operated on the age of 5 days, the defect was
      reconstructed with hairless skin of the mass and she was able to suck after a
      month.

PMID- 14706310
TI  - Oral inverted ductal papilloma.

PMID- 14706311
TI  - Destruction of molar roots by metastasis of multiple myeloma.

PMID- 14706312
TI  - Re: Rowland NH and Schnetler JF. Primary malignant melanoma arising in the dorsum
      of the tongue.

PMID- 14706313
TI  - Double mandibular osteotomy with coronoidectomy for tumours in the parapharyngeal
      space.

PMID- 14706314
TI  - Re: Aesthetic facial surgery/letter by Ilankovan et al./June 2003 issue.

PMID- 14706315
TI  - Calman reforms have had no impact on age at consultant appointment in our
      specialty.

PMID- 14706316
TI  - Incidence of penetration of a blood vessel during inferior alveolar nerve block.

PMID- 14706317
TI  - Re. Haemangioma of the body of the mandible-a case report.

PMID- 14706319
TI  - Spinal shape changes resulting from scoliotic spine surgical instrumentation
      expressed as intervertebral rotations and centers of rotation.
AB  - This paper reports the changes in spinal shape resulting from scoliotic spine
      surgical instrumentation expressed as intervertebral rotations and centers of
      rotation. The objective is to test the hypothesis that the type of spinal
      instrumentation system (Cotrel-Dubousset versus Colorado) does not influence
      these motion parameters. Intervertebral rotations and centers of rotation of the
      scoliotic spines were computed from the pre- and post-operative radiographs of 82
      patients undergoing spinal correction. The three-dimensional (3D) reconstruction
      of six anatomical landmarks was achieved for each of the thoracic and lumbar
      vertebrae. A least-squares approach based on singular value decomposition was
      used to calculate the rigid body transformation parameters. Average centers of
      rotation for all intervertebral levels are located in the neural canal at the mid
      sagittal plane and approximately at the superior endplate level of the inferior
      vertebra. Intervertebral rotations have components in all planes: 6.7 degrees
      (frontal), 5.5 degrees (sagittal) and 4.5 degrees (transverse) RMS for all
      intervertebral levels. Nearly all intervertebral rotations and centers of
      rotation are not significantly different for the two instrumentation systems.
      Various intervertebral rotations and 3D reconstruction errors were simulated on a
      theoretical model of a lumbar functional unit to assess the proposed method.
      Intervertebral rotation errors were 1.7 degrees when simulating 3D errors of 3mm
      on the position of the landmarks. Maximum errors for the position of centers of
      rotation were below 1cm in the case of intervertebral rotations larger than 2.5
      degrees (most cases), but were larger (38 mm) for small intervertebral rotations
      (<1 degrees ). The type of instrumentation system did not influence
      intervertebral rotations and centers of rotation. These results provide valuable
      data for the development and validation of simulation models for surgical
      instrumentation of idiopathic scoliosis.

PMID- 14706320
TI  - Similarity in the fatigue behavior of trabecular bone across site and species.
AB  - Within the context of improving knowledge of the structure-function relations for
      trabecular bone for cyclic loading, we hypothesized that the S-N curve for cyclic
      compressive loading of trabecular bone, after accounting for differences in
      monotonic strength behavior, does not depend on either site or species. Thirty
      five cores of fresh-frozen elderly human vertebral trabecular bone, harvested
      from nine donors (mean+/-S.D., age=74+/-17 years), were biomechanically tested in
      compression at sigma/E(0) values (ratio of applied stress to pre-fatigue elastic
      modulus) ranging from 0.0026 to 0.0070, and compared against literature data (J.
      Biomech. Eng. 120 (1998) 647-654) for young bovine tibial trabecular bone (n=37).
      As reported for the bovine bone, the number of cycles to failure for the human
      vertebral bone was related to sigma/E(0) by a power-law relation (r(2)=0.54,
      n=35). Quantitative comparison of these data against those reported for the
      bovine bone supported our hypothesis. Namely, when the differences in mean
      monotonic yield strain between the two types of bone were accounted for, a single
      S-N curve worked well for the pooled data (r(2)=0.75, n=72). Since elderly human
      vertebral and young bovine tibial trabecular bone represent two very different
      types of trabecular bone in terms of volume fraction and architecture, these
      findings suggest that the dominant failure mechanisms in trabecular bone for
      cyclic loading occur at the ultrastructural level.

PMID- 14706321
TI  - Experimental and theoretical investigation of directional permeability of human
      vertebral cancellous bone for cement infiltration.
AB  - The use of acrylic polymers in infiltrating the porous bone structure is an
      emerging procedure for the augmentation of osteoporotic vertebrae. Although this
      procedure is employed frequently, it is performed based on empirical knowledge,
      and therefore, does not take into consideration the porosity-dependent
      permeability of human vertebral cancellous bone. The purpose of this study was
      to: (a). experimentally and theoretically investigate interdependence of the
      vertebral cancellous bone permeability and porosity, and (b). examine if the bone
      permeability of spinal cancellous bone can be predicted using bone mineral
      density measurements. If these relations can be established, they can be useful
      in optimizing the injection conditions for predicable cement infiltration. To
      determine the porosity-dependent and directional permeability, 34 bone cores-20
      samples in the superior-inferior (SI) direction and 14 in the anterior-posterior
      (AP) direction-were cut from 20 lumbar vertebrae and infiltrated with silicone
      oil with a viscosity matching that of PMMA. The permeability of the cores was
      determined based on Darcy's law. The mean permeability of SI and AP cores was
      4.45+/-1.72 x 10(-8) and 3.44+/-1.26 x 10(-8)m(2), respectively. An interesting
      finding of this study was that the permeability of the AP cores was approximately
      78% of that of SI cores, though the porosity of the SI and AP cores taken from
      the same vertebra was approximately equal. In addition, we provided a theoretical
      model for the porosity-dependent permeability that accurately described non
      linear dependency of the bone permeability and porosity in both directions.
      Although the relation of the bone permeability and porosity was established, bone
      mineral density was a weak predictor of the bone permeability. The experimental
      and theoretical results of this study can be used to understand polymer flow in
      cement infiltration procedures.

PMID- 14706322
TI  - Neural arch load-bearing in old and degenerated spines.
AB  - We validate a technique for measuring neural arch load-bearing in cadaveric
      spines, and use it to test the hypothesis that such load-bearing rises to high
      levels in old and degenerated spines. Fifty-nine cadaveric lumbar motion
      segments, aged 19-92 yr, were subjected to compressive creep loading to reduce
      intervertebral disc water content and height to in vivo levels. The distribution
      of compressive "stress" within the disc was then measured by pulling a miniature
      pressure transducer, side-mounted in a 1.3mm-diameter needle, along its mid
      sagittal diameter. During these measurements, the motion segment was subjected to
      a compressive load of 2 kN, and positioned in 2 degrees of extension to simulate
      erect standing. Measurements of compressive "stress" were integrated over disc
      area, and this force subtracted from the applied 2 kN to give the force resisted
      by the neural arch. An empirical calibration factor was applied to normalise
      results from each disc to values obtained under conditions when all of the
      compressive force could be assumed to pass through the disc. Disc degeneration
      was graded macroscopically on a scale of 1-4. Validation tests showed that
      calculated values of disc loading were proportional to actual applied load
      (r(2)>0.96) and predicted it with errors of 2-8%. Neural arch load-bearing in non
      degenerated specimens was generally less than 20%, but averaged 49% for specimens
      aged over 70 yr. Multiple regression showed that neural arch load bearing
      (%)=14.4 x disc degeneration score+0.46 x age-35. These results indicate a
      substantial shift in vertebral load-bearing with increasing age and degeneration.

PMID- 14706323
TI  - Structural behavior of human lumbar spinal motion segments.
AB  - The objectives of this study were to obtain linearized stiffness matrices, and
      assess the linearity and hysteresis of the motion segments of the human lumbar
      spine under physiological conditions of axial preload and fluid environment.
      Also, the stiffness matrices were expressed in the form of an 'equivalent'
      structure that would give insights into the structural behavior of the spine.
      Mechanical properties of human cadaveric lumbar L2-3 and L4-5 spinal motion
      segments were measured in six degrees of freedom by recording forces when each of
      six principal displacements was applied. Each specimen was tested with axial
      compressive preloads of 0, 250 and 500 N. The displacements were four slow cycles
      of +/-0.5mm in anterior-posterior and lateral displacements, +/-0.35 mm axial
      displacement, +/-1.5 degrees lateral rotation and +/-1 degrees flexion-extension
      and torsional rotations. There were significant increases with magnitude of
      preload in the stiffness, hysteresis area (but not loss coefficient) and the
      linearity of the load-displacement relationship. The mean values of the diagonal
      and primary off-diagonal stiffness terms for intact motion segments increased
      significantly relative to values with no preload by an average factor of 1.71 and
      2.11 with 250 and 500 N preload, respectively (all eight tests p<0.01). Half of
      the stiffness terms were greater at L4-5 than L2-3 at higher preloads. The
      linearized stiffness matrices at each preload magnitude were expressed as an
      equivalent structure consisting of a truss and a beam with a rigid posterior
      offset, whose geometrical properties varied with preload. These stiffness
      properties can be used in structural analyses of the lumbar spine.

PMID- 14706324
TI  - Fluid flow and convective transport of solutes within the intervertebral disc.
AB  - Previous experimental and analytical studies of solute transport in the
      intervertebral disc have demonstrated that for small molecules diffusive
      transport alone fulfils the nutritional needs of disc cells. It has been often
      suggested that fluid flow into and within the disc may enhance the transport of
      larger molecules. The goal of the study was to predict the influence of load
      induced interstitial fluid flow on mass transport in the intervertebral disc. An
      iterative procedure was used to predict the convective transport of
      physiologically relevant molecules within the disc. An axisymmetric, poroelastic
      finite-element structural model of the disc was developed. The diurnal loading
      was divided into discrete time steps. At each time step, the fluid flow within
      the disc due to compression or swelling was calculated. A sequentially coupled
      diffusion/convection model was then employed to calculate solute transport, with
      a constant concentration of solute being provided at the vascularised endplates
      and outer annulus. Loading was simulated for a complete diurnal cycle, and the
      relative convective and diffusive transport was compared for solutes with
      molecular weights ranging from 400 Da to 40 kDa. Consistent with previous
      studies, fluid flow did not enhance the transport of low-weight solutes. During
      swelling, interstitial fluid flow increased the unidirectional penetration of
      large solutes by approximately 100%. Due to the bi-directional temporal nature of
      disc loading, however, the net effect of convective transport over a full diurnal
      cycle was more limited (30% increase). Further study is required to determine the
      significance of large solutes and the timing of their delivery for disc
      physiology.

PMID- 14706325
TI  - In situ intercellular mechanics of the bovine outer annulus fibrosus subjected to
      biaxial strains.
AB  - In situ intercellular strains in the outer annulus fibrosus of bovine caudal
      discs were determined under two states of biaxial strain. Confocal microscopy was
      used to track and capture images of fluorescently labelled nuclei at applied
      Lagrangian strains in the axial direction (E(A)(S)) of 0%, 7.5% and 15% while the
      circumferential direction (E(C)(S)) was constrained to either 0% or -2.5%. The
      position of the nuclear centroids were calculated in each image and used to
      investigate the in situ intercellular mechanics of both lamellar and
      interlamellar cells. The intercellular Lagrangian strains measured in situ were
      non-uniform and did not correspond with the biaxial Lagrangian strains applied to
      the tissue. A row-oriented analysis of intercellular unit displacements within
      the lamellar layers found that the magnitudes of unit displacements between cells
      along a row (delta;(II)) were small (|delta;(IIavg)|=1.6% at E(C)(S)=0%,
      E(A)(S)=15%; |delta;(IIavg)|=3.0% at E(C)(S)=-2.5%, E(A)(S)=15%) with negative
      unit displacements occurring greater than one-third of the time. Evidence of
      interlamellar shear and increased intercellular Lagrangian strains among the
      cells within the interlamellar septa suggested that their in situ mechanical
      environment may be more complex. The in situ intercellular strains of annular
      cells were strongly dependent upon the local structure and behaviour of the
      extracellular matrix and did not correspond with applied tissue strains. This
      knowledge has immediate relevance for in vitro investigations of disc
      mechanobiology, and will also provide a base to investigate the mechanical
      implications of disc degeneration at the cellular level.

PMID- 14706326
TI  - Heat-induced changes in porcine annulus fibrosus biomechanics.
AB  - The intervertebral disc is implicated as the source of low-back pain in a
      substantial number of patients. Because thermal therapy has been thought to have
      a therapeutic effect on collagenous tissues, this technique has recently been
      incorporated into several minimally invasive back pain treatments. However,
      patient selection criteria and precise definition of optimum dose are hindered by
      uncertainty of treatment mechanisms. The purpose of this study was to quantify
      acute changes in annulus fibrosus biomechanics after a range of thermal
      exposures, and to correlate these results with tissue denaturation. Intact
      annulus fibrosus (attached to adjacent vertebrae) from porcine lumbar spines was
      tested ex vivo. Biomechanical behavior, microstructure, peak of denaturation
      endotherm, and enthalpy of denaturation (mDSC) were determined before and after
      hydrothermal heat treatment at 37 degrees C, 50 degrees C, 60 degrees C, 65
      degrees C, 70 degrees C, 75 degrees C, 80 degrees C, and 85 degrees C. Shrinkage
      of excised annular tissue (removed from adjacent vertebrae) was also measured
      after treatment at 85 degrees C. Significant differences in intact annulus
      biomechanics were observed after treatment, but the effects were much smaller in
      magnitude than those observed in excised annulus and those reported previously
      for other tissues. Consistent with this, intact tissue was only minimally
      denatured by treatment at 85 degrees C for 15 min, whereas excised tissue was
      completely denatured by this protocol. Our data suggest that in situ constraint
      imposed by the joint structure significantly retards annular thermal
      denaturation. These findings should aid the interpretation of clinical outcomes
      and provide a basis for the future design of optimum dosing regimens.

PMID- 14706327
TI  - Paraspinal muscle reflex dynamics.
AB  - Neuromuscular control of spinal stability may be represented as a control system
      wherein the paraspinal muscle reflex acts as feedback response to kinetic and
      kinematic disturbances of the trunk. The influence of preparatory muscle
      recruitment for the control of spinal stability has been previously examined, but
      there are few reported studies that characterize paraspinal reflex gain as
      feedback response. In the current study, the input-output dynamics of paraspinal
      reflexes were quantified by means of the impulse response function (IRF), with
      trunk perturbation force representing the input signal and EMG the output signal.
      Surface EMGs were collected from the trunk muscles in response to a brief
      anteriorly directed impact force applied to the trunk of healthy participants.
      Reflex behavior was measured in response to three levels of force impulse, 6.1,
      9.2 and 12.0 Ns, and two different levels of external trunk flexion preload, 0
      and 110 N anterior force. Reflex EMG was quantifiable in response to 91% of the
      perturbations. Mean reflex onset latency was 30.7+/-21.3 ms and reflex amplitude
      increased with perturbation amplitude. Impulse response function gain, G(IRF),
      was defined as the peak amplitude of the measured IRF and provided a consistent
      measure of response behavior. EMG reflex amplitude and G(IRF) increased with
      force impulse. Mean G(IRF) was 2.27+/-1.31% MVC/Ns and demonstrated declining
      trend with flexion preload. Results agree with a simple systems model of the
      neuromechanical feedback behavior. The relative contribution of the reflex
      dynamics to spinal stability must be investigated in future research.

PMID- 14706328
TI  - Lifting over an obstacle: effects of one-handed lifting and hand support on trunk
      kinematics and low back loading.
AB  - Mechanical loading of the low back during lifting is a common cause of low back
      pain. In this study two-handed lifting is compared to one-handed lifting (with
      and without supporting the upper body with the free hand) while lifting over an
      obstacle. A 3-D linked segment model was combined with an EMG-assisted trunk
      muscle model to quantify kinematics and joint loads at the L5S1 joint. Peak total
      net moments (i.e., the net moment effect of all muscles and soft tissue spanning
      the joint) were found to be 10+/-3% lower in unsupported one-handed lifting
      compared to two-handed lifting, and 30+/-8% lower in supported compared to
      unsupported one-handed lifting. L5S1 joint forces also showed reductions, but not
      of the same magnitude (18+/-8% and 15+/-10%, respectively, for compression
      forces, and 15+/-17% and 11+/-14% respectively, for shear forces). Those
      reductions of low back load were mainly caused by a reduction of trunk and load
      moment arms relative to the L5S1 joint during peak loading, and, in the case of
      hand support, by a support force of about 250 N. Stretching one leg backward did
      not further reduce low back load estimates. Furthermore, one-handed lifting
      caused an 6+/-8 degrees increase in lateral flexion, a 9+/-5 degrees increase in
      twist and a 6+/-6 degrees decrease in flexion. Support with the free hand caused
      a small further increase in lumbar twisting. It is concluded that one-handed
      lifting, especially with hand support, reduces L5S1 loading but increases
      asymmetry in movements and moments about the lumbar spine.

PMID- 14706329
TI  - Neutral zone and range of motion in the spine are greater with stepwise loading
      than with a continuous loading protocol. An in vitro porcine investigation.
AB  - Biomechanical testing of the spine has traditionally been performed to help
      understand the normal function of the spine as well as to evaluate the effects of
      injury and surgical procedures on spinal behaviour. The overall objective of this
      investigation was to compare traditional stepwise loading with the recently
      introduced continuous loading protocol, determining the effect of loading
      protocol on the mechanical behaviour of the spine. For all tests, a custom spine
      testing machine was used to apply pure moments of flexion extension, axial
      rotation, and lateral bending to a maximum of 2 Nm, using six porcine cervical
      spine specimens (C2-C4). Motions of C2 with respect to C4 were measured with an
      optoelectronic camera system. Motion parameters calculated were range of motion
      (ROM), neutral zone (NZ), and the ratio of NZ and ROM. The continuous loading
      protocol had smaller values for all motion parameters in each loading direction
      (p<0.05). ROM for the continuous test ranged between 88% and 93% of that of
      stepwise for the three loading directions. The continuous protocol NZ was 56-75%
      of that of the stepwise test. The findings of the study demonstrate that the two
      loading protocols provide differing spinal behaviours.

PMID- 14706330
TI  - No T without D3: a critical role for cyclin D3 in normal and malignant precursor
      T cells.
AB  - A definitive knockout reported in this issue of Cancer Cell by Sicinska et al.
      reveals an unsuspected role for cyclin D3 in normal T cell development and
      suggests new therapeutic possibilities in precursor T cell leukemia.

PMID- 14706331
TI  - Restoring functions of tumor suppressors with small molecules.
AB  - Developing small molecule inhibitors of oncoproteins, which are activated in
      tumor cells, is a newly popular strategy for cancer-related drug discovery. The
      complementary strategy, developing small molecules that restore the function of
      missing tumor suppressors, is much more difficult to realize. However, in this
      issue of Cancer Cell, Kau et al. report the discovery of small molecules that
      reverse some cellular consequences of the loss of the tumor suppressor PTEN.

PMID- 14706332
TI  - Rhabdomyosarcomagenesis-Novel pathway found.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Recent
      work presented in this issue of Cancer Cell by Fleischmann et al. on gene
      knockout mice revealed a remarkable molecular pathway for
      rhabdomyosarcomagenesis, in which Trp53/Fos double mutant mice developed RMS of
      the facial and orbital regions with high penetrance. This finding may provide
      novel molecular mechanisms for Rhabdomyosarcomagenesis and therapeutic
      implications for RMS patients.

PMID- 14706333
TI  - Defective autophagy leads to cancer.
AB  - Cellular proteins are degraded within two distinct compartments: the proteasome
      and the lysosome. Alterations in proteasomal degradation can contribute to
      carcinogenesis. In contrast, alterations in autophagic protein degradation
      through the lysosome have not been linked to cancer. Now two reports demonstrate
      that the autophagic gene, Beclin 1, is a haploinsufficient tumor suppressor gene.
      These new data suggest that autophagic degradation provides an important
      mechanism to prevent cellular transformation.

PMID- 14706334
TI  - p21Waf1/Cip1 as a therapeutic target in breast and other cancers.
AB  - The cyclin kinase inhibitor p21, originally described as a universal inhibitor of
      cyclin-dependent kinases, has since been shown to have additional functions other
      than CDK inhibition. It is likely that a key role of p21 is to keep cells alive
      after DNA damage and subsequent p53 induction, in order for the cell to effect
      repairs. Thus, the increase in p21 seen in some cancers may impart these cells
      with a survival advantage. Here we discuss how this antiapoptotic aspect of p21
      makes it an attractive target for cancer therapy; attenuation of p21 in malignant
      cells may subvert the normal repair process induced by DNA-damaging
      chemotherapeutic agents and thus make such drugs more effective.

PMID- 14706335
TI  - Targeting cyclooxygenase-2 in human neoplasia: rationale and promise.

PMID- 14706336
TI  - Preinvasive and invasive ductal pancreatic cancer and its early detection in the
      mouse.
AB  - To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we
      directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse
      pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions
      that recapitulate the full spectrum of human pancreatic intraepithelial
      neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The
      PanINs are highly proliferative, show evidence of histological progression, and
      activate signaling pathways normally quiescent in ductal epithelium, suggesting
      potential therapeutic and chemopreventive targets for the cognate human
      condition. At low frequency, these lesions also progress spontaneously to
      invasive and metastatic adenocarcinomas, establishing PanINs as definitive
      precursors to the invasive disease. Finally, mice with PanINs have an
      identifiable serum proteomic signature, suggesting a means of detecting the
      preinvasive state in patients.

PMID- 14706337
TI  - Requirement for cyclin D3 in lymphocyte development and T cell leukemias.
AB  - The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle
      machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is
      overexpressed in several human lymphoid malignancies. In order to determine the
      function of cyclin D3 in development and oncogenesis, we generated and analyzed
      cyclin D3-deficient mice. We found that cyclin D3(-/-) animals fail to undergo
      normal expansion of immature T lymphocytes and show greatly reduced
      susceptibility to T cell malignancies triggered by specific oncogenic pathways.
      The requirement for cyclin D3 also operates in human malignancies, as knock-down
      of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving
      from immature T lymphocytes. These studies point to cyclin D3 as a potential
      target for therapeutic intervention in specific human malignancies.

PMID- 14706338
TI  - A chemical genetic screen identifies inhibitors of regulated nuclear export of a
      Forkhead transcription factor in PTEN-deficient tumor cells.
AB  - The PI3K/PTEN/Akt signal transduction pathway plays a key role in many tumors.
      Downstream targets of this pathway include the Forkhead family of transcription
      factors (FOXO1a, FOXO3a, FOXO4). In PTEN null cells, FOXO1a is inactivated by
      PI3K-dependent phosphorylation and mislocalization to the cytoplasm, yet still
      undergoes nucleocytoplasmic shuttling. Since forcible localization of FOXO1a to
      the nucleus can reverse tumorigenicity of PTEN null cells, a high-content,
      chemical genetic screen for inhibitors of FOXO1a nuclear export was performed.
      The compounds detected in the primary screen were retested in secondary assays,
      and structure-function relationships were identified. Novel general export
      inhibitors were found that react with CRM1 as well as a number of compounds that
      inhibit PI3K/Akt signaling, among which are included multiple antagonists of
      calmodulin signaling.

PMID- 14706339
TI  - Rhabdomyosarcoma development in mice lacking Trp53 and Fos: tumor suppression by
      the Fos protooncogene.
AB  - The Fos protein, a major component of the AP-1 transcription factor, is essential
      for osteoclast differentiation, acts as an oncogene, potentiates transforming
      signals, and controls invasive growth and angiogenesis during tumor progression.
      To investigate a potential genetic interaction between the Trp53 and Fos
      pathways, Trp53/Fos double knockout mice were generated. These mice develop
      highly proliferative and invasive rhabdomyosarcomas of the facial and orbital
      regions, with more than 90% penetrance at 6 months of age. Rhabdomyosarcoma cell
      lines established from the primary tumors express characteristic muscle-specific
      markers, and reexpression of Fos is associated with enhanced apoptosis in vitro.
      Moreover, Fos is able to repress Pax7 expression in rhabdomyosarcoma cell lines
      and primary myoblasts, suggesting a molecular link to genetic alterations
      involved in human rhabdomyosarcomas.

PMID- 14706340
TI  - Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of
      chromosomal instability.
AB  - In this study, we show that the formation of polyploidy following sustained
      mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent
      proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced
      not only in polyploid cells created by sustained mitotic spindle damage, but also
      in 21 (31.3%) of 67 human colon adenocarcinomas tested. Importantly, the
      introduction of hBubR1 triggers the apoptosis of polyploid cells formed by
      aberrant exit from mitosis and inhibits the growth of tumors established with
      these cells in athymic nude mice. These results suggest that hBubR1-mediated
      apoptosis prevents the propagation of cells that breach the mitotic checkpoint
      and that the control of hBubR1 protein level is an important factor in the
      acquisition of preneoplastic polyploidy.

PMID- 14706341
TI  - Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin,
      increased transcriptional activity of beta-catenin, and enhanced tumor cell
      invasion.
AB  - EGF receptor (EGFR) overexpression correlates with metastasis in a variety of
      carcinomas, but the underlying mechanisms are poorly understood. We demonstrated
      that EGF disrupted cell-cell adhesion and caused epithelial-to-mesenchymal
      transition (EMT) in human tumor cells overexpressing EGFR, and also induced
      caveolin-dependent endocytosis of E-cadherin, a cell-cell adhesion protein.
      Chronic EGF treatment resulted in transcriptional downregulation of caveolin-1
      and induction of the transcriptional repressor Snail, correlating with
      downregulation of E-cadherin expression. Caveolin-1 downregulation enhanced beta
      catenin-TCF/LEF-1 transcriptional activity in a GSK-3beta-independent manner.
      Antisense RNA-mediated reduction of caveolin-1 expression in EGFR-overexpressing
      tumor cells recapitulated these EGF-induced effects and enhanced invasion into
      collagen gels. We propose that EGF-induced negative regulation of caveolin-1
      plays a central role in the complex cellular changes leading to metastasis.

PMID- 14706343
TI  - Ku86 deficiency leads to reduced intrachromosomal homologous recombination in
      vivo in mice.
AB  - Ku70 and Ku86 together with DNA-PKcs form the DNA-dependent protein kinase (DNA
      PK) complex that is involved in DNA double-strand break repair by nonhomologous
      end joining. We investigated the effect of Ku86 mutation on intrachromosomal
      homologous recombination (HR) resulting in deletions in vivo in mice. We
      quantified such deletion events using a phenotypic pigmentation assay. Deletion
      of one copy of a 70 kb DNA duplication in the pink-eyed unstable (pun) allele
      results in reversion to the wildtype pink-eyed dilution (p) gene, allowing black
      pigment accumulation in cells of the retinal pigment epithelium (RPE). We found
      that the frequency of homologous recombination was significantly reduced in Ku86
      deficient mice. Furthermore, the proliferation of cells in which recombination
      events occurred was reduced and developmentally delayed in the Ku86 deficient
      mice. These data indicate a role for Ku86 directly or indirectly in homologous
      recombination in vivo.

PMID- 14706344
TI  - Induction and repair of radiation-induced DNA double-strand breaks in human
      fibroblasts are not affected by terminal differentiation.
AB  - It was studied for human skin fibroblasts, whether the induction or repair of DNA
      double-strand breaks (dsb) depend on the differentiation status. These studies
      were performed (a) with a fibroblast strain (HSF1) kept in progenitor state
      (mitotic fibroblasts, MF) or triggered to premature terminal differentiation
      (postmitotic fibrocytes, PMF) by exposure to mitomycin C or (b) with 20
      fibroblast strains differing intrinsically in their differentiation status. The
      differentiation status was quantified by determining the fraction of postmitotic
      fibrocytes by light microscopy. DNA dsb were measured by constant-field gel
      electrophoresis, and the fraction of apoptotic cells by comet assay. MF and PMF
      cultures of HSF1 cells were irradiated with X-ray doses up to 160 Gy, and dsb
      were measured either immediately after irradiation or after a repair incubation
      of 4 or 24 h. There were a difference neither in the number of initial nor
      residual dsb. PMF cultures, however, showed a slightly higher number of dsb
      already present in non-irradiated cells, which was measured to result from a
      small fraction of 5% apoptotic cells. The 20 analysed fibroblast strains showed a
      substantial variation in the fraction of postmitotic fibrocytes (9-51%) as well
      as in the number of dsb remaining at 24 h after irradiation (1.9-4.9%), but there
      was no correlation between these two parameters. These data demonstrate that for
      fibroblasts the terminal differentiation has an effect neither on the induction
      nor the repair of radiation-induced dsb. This result indicates that the variation
      in dsb-repair capacity previously observed for fibroblast strains and which was
      considered to be the main cause for the variation in the cellular
      radiosensitivity, cannot be ascribed to differences in the differentiation
      status.

PMID- 14706345
TI  - Characterization of human ribosomal protein S3 binding to 7,8-dihydro-8
      oxoguanine and abasic sites by surface plasmon resonance.
AB  - The human ribosomal protein S3 (hS3) possesses multifunctional activities that
      are involved in both protein translation, as well as the ability of cleaving
      apurinic/apyrimidinic (AP) DNA via a beta-elimination reaction. We recently
      showed that hS3 also has a surprising binding affinity for an 7,8-dihydro-8
      oxoguanine (8-oxoG) residue embedded in a 5' end labeled 37mer DNA
      oligonucleotide. To understand the interaction of hS3 and DNA templates
      containing 8-oxoG, we carried out real-time analysis using surface plasmon
      resonance (SPR). Notably, hS3 was found to have an apparent three orders of
      magnitude higher binding affinity (KD) for 8-oxoG than the human N-glycosylase/AP
      lyase base excision repair (BER) enzyme OGG1. An even more dramatic five orders
      of magnitude higher binding affinity for AP DNA was found for hS3 as opposed to
      hOGG1. These results suggest that ribosomal protein hS3 may have a
      multifunctional role that may also affect functions associated with DNA base
      excision repair transactions.

PMID- 14706346
TI  - Nucleotide excision repair deficiency causes elevated levels of chromosome gain
      in Saccharomyces cerevisiae.
AB  - Aneuploidy is the most frequent aberration observed in tumor cells, and underlies
      many debilitating and cancer-prone congenital disorders. Aneuploidy most often
      arises as a consequence of chromosomal non-disjunction, however, little is known
      about the genetic and epigenetic factors that affect the chromosomal segregation
      process. As many cancer-prone syndromes are associated with defects in DNA repair
      pathways we decided to investigate the relationship between DNA repair in
      mutation avoidance pathways, namely base and nucleotide excision, and mismatch
      repair (MMR), and aneuploidy in the yeast Saccharomyces cerevisiae. Isogenic
      haploid and diploid DNA repair deficient yeast strains were constructed, and
      spontaneous levels of intra- and inter-chromosomal recombination, forward
      mutation, chromosome gain, and loss were measured. We show that the nucleotide
      excision repair (NER) pathway is required for accurate chromosomal disjunction.
      In the absence of Rad1, Rad2, or Rad4, spontaneous levels of chromosome XV gain
      were significantly elevated in both haploid and diploid mutant strains. Thus,
      chromosome gain may be an additional cancer predisposing event in NER deficient
      patients.

PMID- 14706347
TI  - Functional and physical interactions between ERCC1 and MSH2 complexes for
      resistance to cis-diamminedichloroplatinum(II) in mammalian cells.
AB  - Bulky DNA lesions are mainly repaired by nucleotide excision repair (NER), in
      which the interaction of ERCC1 with XPA protein recruits the ERCC1-XPF complex,
      which acts as a structure-specific endonuclease in the repair process. However,
      additional functions besides NER have been suggested for the ERCC1-XPF complex,
      because ERCC1- or XPF-deficient rodent cells are significantly more sensitive to
      DNA interstrand cross-linking (ICL) agents such as cis
      diamminedichloroplatinum(II) (CDDP) than any other NER-deficient cells and
      because ERCC1-deficient mice suffer a more severe phenotype than XPA-deficient
      mice. By using RNA interference we show here that suppression of ERCC1 expression
      increases the sensitivity of xeroderma pigmentosum group A (XPA)-deficient human
      cells to CDDP but not to UV. This increased sensitivity to CDDP is observed in
      mouse cells defective in Xpa as well but not in cells defective both in Xpa and
      the mismatch repair gene Msh2. These data suggest that ERCC1 and MSH2 are
      involved co-operatively in CDDP resistance in mammalian cells. As a possible
      molecular basis, we show further a physical interaction between endogenous ERCC1
      and MSH2 complexes in HeLa cell extracts. Using tagged ERCC1 in COS7 cells, the
      minimum region in ERCC1 necessary for the immuno-precipitation of MSH2 is turned
      out to be the carboxyl-terminal domain between the 184th and 260th amino acid,
      which is partly overlapping with the XPF-binding domain of ERCC1. This
      interaction may be important in additional functions of ERCC1-XPF including the
      repair of CDDP-induced DNA damage.

PMID- 14706348
TI  - Base J, found in nuclear DNA of Trypanosoma brucei, is not a target for DNA
      glycosylases.
AB  - Base excision repair (BER) is an evolutionarily conserved system which removes
      altered bases from DNA. The initial step in BER is carried out by DNA
      glycosylases which recognize altered bases and cut the N-glycosylic bond between
      the base and the DNA backbone. In kinetoplastid flagellates, such as Trypanosoma
      brucei, the modified base beta-D-glucosyl-hydroxymethyluracil (J) replaces a
      small percentage of thymine residues, predominantly in repetitive telomeric
      sequences. Base J is synthesized at the DNA level via the precursor 5
      hydroxymethyluracil (5-HmU). We have investigated whether J in DNA can be
      recognized by DNA glycosylases from non-kinetoplastid origin, and whether the
      presence of J and 5-HmU in DNA has required modifications of the trypanosome BER
      system. We tested the ability of 15 different DNA glycosylases from various
      origins to excise J or 5-HmU paired to A from duplex oligonucleotides. No
      excision of J was found, but 5-HmU was excised by AlkA and Mug from Escherichia
      coli and by human SMUG1 and TDG, confirming previous reports. In a combination of
      database searches and biochemical assays we identified several DNA glycosylases
      in T. brucei, but in trypanosome extracts we detected no excision activity
      towards 5-HmU or ethenocytosine, a product of oxidative DNA damage and a
      substrate for Mug, TDG and SMUG1. Our results indicate that trypanosomes have a
      BER system similar to that of other organisms, but might be unable to excise
      certain forms of oxidatively damaged bases. The presence of J in DNA does not
      require a specific modification of the BER system, as this base is not recognized
      by any known DNA glycosylase.

PMID- 14706349
TI  - Mutagenicity of the cytidine analog zebularine in Escherichia coli.
AB  - We have examined the mutagenic properties of zebularine, a cytidine analog
      lacking the amino group at C-4 that has potential use in chemotherapy. Because
      the hydrate is a strong inhibitor of cytidine deaminase, its use can enhance the
      potency of other cytosine based compounds such as 5-azacytidine (5AzaC) and
      cytosine arabinoside (ara-C) that are inactivated by cytidine deaminase. Using
      the newly developed rpoB/Rifr system in Escherichia coli, we examined base
      substitution mutations caused by zebularine in the chromosomal rpoB gene.
      Zebularine is a potent mutagen that causes mainly G : C --> A : T transitions and
      favors certain hotspots. Mutations are not specific to the rpoB gene, since there
      is also a strong induction of mutations in the thyA gene. In the absence of
      mismatch repair, zebularine induces both base substitutions and frame shifts at
      rates well above those seen in wild-type strains treated with zebularine or in
      mismatch repair deficient strains without treatment. The nature of these induced
      mutations indicates that zebularine is stimulating the induction of increased
      replication errors, in addition to the targeted G : C --> A : T mutations, and
      that these errors are normally repaired by the mismatch repair system.

PMID- 14706350
TI  - Multiple uracil-DNA glycosylase activities in Deinococcus radiodurans.
AB  - The extremely radiation resistant bacterium, Deinococcus radiodurans, contains a
      spectrum of genes that encode for multiple activities that repair DNA damage. We
      have cloned and expressed the product of three predicted uracil-DNA glycosylases
      to determine their biochemical function. DR0689 is a homologue of the Escherichia
      coli uracil-DNA glycosylase, the product of the ung gene; this activity is able
      to remove uracil from a U : G and U : A base pair in double-stranded DNA and
      uracil from single-stranded DNA and is inhibited by the Ugi peptide. DR1751 is a
      member of the class 4 family of uracil-DNA glycosylases such as those found in
      the thermophiles Thermotoga maritima and Archaeoglobus fulgidus. DR1751 is also
      able to remove uracil from a U : G and U : A base pair; however, it is
      considerably more active on single-stranded DNA. Unlike its thermophilic
      relatives, the enzyme is not heat stable. Another putative enzyme, DR0022, did
      not demonstrate any appreciable uracil-DNA glycosylase activity. DR0689 appears
      to be the major activity in the organism based on inhibition studies with D.
      radiodurans crude cell extracts utilizing the Ugi peptide. The implications for
      D. radiodurans having multiple uracil-DNA glycosylase activities and other
      possible roles for these enzymes are discussed.

PMID- 14706351
TI  - The C. elegans gene pme-5: molecular cloning and role in the DNA-damage response
      of a tankyrase orthologue.
AB  - Tankyrases are recently identified proteins characterized by ankyrin repeats and
      a poly(ADP-ribose) polymerase (PARP) signature motif. In vertebrates, tankyrases
      mediate protein-protein interactions via the ankyrin domain. Many partners have
      been identified that could function in telomere maintenance, signal transduction
      in vesicular transport, and cell death. To further our knowledge of tankyrases
      and to study their function in development, we sought and found a tankyrase
      related gene in Caenorhabditis elegans that we named pme-5 (poly(ADP-ribose)
      metabolism enzyme-5). The protein encoded includes a large ankyrin domain and a
      catalytic PARP domain containing the well-conserved PARP signature sequence and
      the regulatory region. Unlike other tankyrases, PME-5 lacks a sterile-alpha
      module (SAM), but has a coiled coil domain which may mediate oligomerization. We
      also found that pme-5 mRNA is alternatively spliced at the fifth exon, producing
      a long (PME-5L) and a short (PME-5S) transcript. Both isoforms are constitutively
      expressed during the life cycle of C. elegans. We also show DNA damage increases
      expression of pme-5, a response that requires the DNA damage checkpoint gene hus
      1. Moreover, DNA damage-induced germ cell apoptosis was slightly increased in pme
      5(RNAi) hermaphrodites. Altogether, these data indicate that pme-5 is part of a
      DNA damage response pathway which leads to apoptosis in C. elegans.

PMID- 14706352
TI  - The discovery that xeroderma pigmentosum (XP) results from defective nucleotide
      excision repair.
AB  - Most forms of the human hereditary disease xeroderma pigmentosum (XP) are due to
      a defect in nucleotide excision repair of DNA damage in skin cells associated
      with exposure to sunlight. This discovery by James Cleaver had an important
      impact on our understanding of nucleotide excision repair in mammals.

PMID- 14706353
TI  - DNA repair community connects at Cortona: researchers focus on protein networks,
      network topology and molecular signatures.

PMID- 14706354
TI  - In this issue... neurosurgical education.

PMID- 14706356
TI  - Competency-based training in neurosurgery: the next revolution in medical
      education.

PMID- 14706371
TI  - Medical professional liability crisis.

PMID- 14706372
TI  - Extraforaminal lumbar arterial anatomy.
AB  - BACKGROUND: There are few studies carried out to reveal lumbar arterial anatomy.
      The studies of vascular anatomy of the lumbar zone are usually based on the
      angiographic imaging methods and barium injected radiographic sections of human
      specimens. METHODS: Upon the recent breakthroughs in the microscopic anatomic
      dissections, the vascular structure of this zone is examined in 16 cadavers.
      Arterial anatomies of the extraforaminal zones of 80 lumbar vertebral objects
      were studied. RESULTS: In each segment, lumbar artery, extraforaminal branches of
      the lumbar artery and the spinal (foraminal) branch were described. The spinal
      branch is originated from lumbar artery and extends as the dorsal branch. The
      dorsal branch is divided into 4 branches: ganglionic, transverse, ascending, and
      descending. Diameters of the lumbar artery, spinal, dorsal, and ganglionic
      branches were measured at each stage. The mean diameter of the lumbar artery was
      2.7 mm, the dorsal branch was 2.0 mm, the foraminal branch was 1.9 mm, and the
      ganglionic branch was 1.0 mm, respectively. CONCLUSION: Knowledge of lumbar
      arterial anatomy is needed for carrying out a successful surgical operation and
      reducing complications.

PMID- 14706374
TI  - Spinal neurinomas: retrospective analysis and long-term outcome of 179
      consecutively operated cases and review of the literature.
AB  - BACKGROUND: We present a series of 179 spinal neurinomas consecutively observed
      at the Department of Neurosurgery at the University of Florence for a period of
      30 years (between 1967 and 1997). We decided to limit the retrospective study to
      obtain at least 5 years of follow-up. Therefore, 20 additional neurinomas treated
      between 1997 and 2002 were excluded. METHODS: All the cases are evaluated under
      statistical, clinical, neuroradiological, and surgically technical profiles based
      on data from clinical records and from periodic check-ups after surgery. In
      particular, the results are analyzed on the basis of an accurate pre- and
      postsurgical evaluation using Karnofsky's scale and Kleklamp-Samii's scoring
      system. RESULTS: We treated 179 spinal neurinomas in 152 (93 male and 59 female)
      patients. The mean age was 44.3. In 33 cases the neurinoma was sited in the
      cervical tract, in 59 cases in the dorsal tract, and in 87 cases in the lumbo
      sacral tract. Eleven patients harbored Recklinghausen's neurofibromatosis (7 NF1
      and 4 NF2 of which 1 was intramedullary). In 123 cases the neurinoma was
      intradural, in 11 cases it was extradural, in 2 intra/extradural, in 9 it had a
      dumbbell form, and in 2 cases it was intramedullary; the remaining cases had
      neurofibromatosis. The most common presurgical symptom was segmental pain. Total
      removal of the lesion was possible in the first operation for 174 neurinomas. We
      encountered 3 cases of malignant neurinoma of which 1 was in NF2. The result of
      surgery was recovery in 108 cases; 2 patients with NF2 died, and local recurrence
      occurred even after total exeresis (excision) and radiotherapy in the cases of
      malignant neurinoma. CONCLUSIONS: Schwannomas represent the most frequent tumor
      lesions of the spine with prevalence for the cervical-inferior tract and the
      dorso-lumbar passage. Intramedullary neurinomas are rarely observed. The total
      surgical removal of neurinomas is often an attainable goal, and clinical
      improvement is the common outcome with exception to malignant forms and NF2
      neurofibromatosis. We describe a series of 179 treated schwannomas.

PMID- 14706378
TI  - The effects of tyrphostine Ag 556 on experimental spinal cord ischemia
      reperfusion injury.
AB  - BACKGROUND: To investigate the effects of Tyrphostin Ag 556 on spinal cord
      ischemia reperfusion injury. METHODS: The inhibition of tyrosine kinase may
      represent a novel approach in the treatment of spinal cord ischemia reperfusion
      injury. Recently, a family of tyrosine kinase inhibitors, the tyrphostins, has
      been successfully used in models of endotoxemia, peritonitis, and hypovolemic
      shock. MATERIALS AND METHODS: Twenty-four Wistar rats were used in the study.
      Rats were divided into 4 groups of 6 animals. The groups were named as sham
      operated group, injury group, vehicle group, and treatment group. Clamping of the
      abdominal aorta was performed for 45 minutes with all of the groups except sham
      operated group. All of the rats were sacrificed 24 hours after the operation for
      biochemical and ultrastructural studies. RESULTS: Tyrphostin Ag 556 treatment was
      found effective on experimental spinal cord ischemia reperfusion injury. The
      Malondialdehyde (MDA) values of the treatment group were statistically
      significant lower then the other reperfusion injury groups. The histologic
      examination showed better cellular structure in the treatment group than the
      other reperfusion injury groups. The neurologic scores of the treatment group
      also improved after treatment. CONCLUSIONS: Tyrphostin Ag 556 alters spinal cord
      ischemia reperfusion injury by inhibiting protein kinases. Further investigations
      will be required to determine the long-term effects of this drug.

PMID- 14706380
TI  - Duraplasty: our current experience.
AB  - BACKGROUND: A large variety of biologic and artificial materials have been
      suggested as dural substitutes. However, no ideal material for dural repair in
      neurosurgical procedures has been identified. The authors report their experience
      with Tutoplast processed dura and pericardium. METHODS: This study is designed to
      evaluate Tutoplast dura and pericardium. The study population was composed of 250
      consecutive patients who underwent cerebral duraplasty with these homologous
      materials between 1996 and 1998. The average follow-up was 5.4 years. RESULTS: We
      have observed only four complications with uncertain relationship with the dural
      implant. These resulted in complete recovery. CONCLUSIONS: We support the
      efficacy and safety of this natural dural substitute treated with Tutoplast
      method.

PMID- 14706382
TI  - Small petrosal approach to the middle portion of the mediobasal temporal region:
      technical case report.
AB  - BACKGROUND: The mediobasal temporal region has been divided into three portions:
      anterior, middle, and posterior. Surgical access, especially to the middle
      portion, presents a formidable challenge to neurosurgeons, and much controversy
      still exists regarding the selection of the surgical approach to this region.
      CASE REPORT: We used the small petrosal approach to the middle portion of the
      mediobasal temporal region in a patient with intractable seizures caused by a
      cavernous angioma in this region. Using this approach, we selectively removed the
      lesion without postoperative deficits. CONCLUSIONS: The small petrosal approach
      was found to be useful and safe as an alternative technique for selective removal
      of the lesion in the middle portion of the mediobasal temporal region.

PMID- 14706384
TI  - Cerebral metastasis from angiosarcoma of the aortic wall: case report.
AB  - BACKGROUND: Primary or metastatic cerebral angiosarcoma is extremely rare, and
      only limited cases have been reported. The authors here describe a case of
      angiosarcoma, which was initially identified and diagnosed by the cerebral
      metastatic lesion; later examinations suggested that the primary site was the
      abdominal aorta. CASE DESCRIPTION: A 53-year-old man, who had suffered an
      abdominal aortic aneurysm 2 months earlier, experienced a sudden onset of left
      sided hemifacial convulsion and dysarthric speech. Computed tomography (CT)
      showed a hemorrhagic mass lesion with perifocal edema in the right frontal lobe.
      Magnetic resonance imaging (MRI) showed a regionally marked hypointensity in the
      mass lesion on both T1- and T2-weighted images, which might suggest hemosiderin
      deposition. The tumor was removed in its entirety. Pathologic examination
      revealed an old hematoma with a hemosiderin deposit containing markedly atypical
      tumor cells, and angiosarcoma was diagnosed. Resection of the abdominal aortic
      aneurysm and iliac bone biopsy were performed and angiosarcoma was recognized in
      each surgical specimen. Based on clinical and pathologic findings, the primary
      site was considered to be the abdominal aorta. CONCLUSIONS: Clinicians should be
      aware of this rare histologic type of tumor. Unique MRI findings such as those
      obtained in our case might be useful for differentiating this condition from
      other intracranial neoplasms.

PMID- 14706385
TI  - Intramedullary spinal cord metastasis of lung adenocarcinoma presenting as Brown
      Sequard syndrome.
AB  - BACKGROUND: It is extremely rare for cancer to present first as an intramedullary
      spinal cord metastasis. Furthermore, because it is unlikely for spinal cord
      neoplasm to present acutely, an acute presentation may signify metastatic disease
      and should be considered in the initial differential diagnosis. METHODS: The
      authors present a case of a 59-year-old man presenting with Brown-Sequard
      syndrome and in whom metastatic lung adenocarcinoma to the spinal cord was
      subsequently discovered. Review of the literature reveals this case to be one of
      only a very few where intramedullary tumor was the first manifestation of
      metastatic disease. RESULTS: The mainstay of treatment for intramedullary spinal
      metastases remains steroids, radiation, and chemotherapy, though no well-designed
      study compares these modalities by long-term survival and functional results.
      This patient underwent local radiation and systemic chemotherapy following
      surgical resection. CONCLUSIONS: This patient had no preoperative signs
      suggesting disease in other organs, making the diagnosis of lung adenocarcinoma
      metastatic to the intramedullary cord surprising, especially given the extremely
      rare incidence of spinal intramedullary metastatic disease. However, the patient
      had an acute presentation, uncommon for primary neoplasm, which may be an
      indication of metastatic disease.

PMID- 14706386
TI  - Primary spinal oligoastrocytoma: a case report.
AB  - BACKGROUND: Primary oligoastrocytomas of the spinal cord are rare, and the
      treatment options for low-grade intramedullary tumors are controversial.
      DESCRIPTION: A 10-year-old girl presented with thoracic scoliosis. Magnetic
      resonance imaging (MRI) revealed an enhancing intramedullary mass lesion
      extending from C-5 to T-5, associated with whole spine syringomyelia and
      syringobulbia. (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET)
      showed high uptake in the lesion. The patient underwent C-5 to T-5 laminoplastic
      laminotomy and subtotal removal of the tumor. Histologic examination revealed
      that the tumor was an oligoastrocytoma without anaplastic findings. Genetic
      analysis revealed loss of heterozygosity of 1p and 19q but not 10q, which is
      characteristic of oligodendroglial tumors. CONCLUSIONS: To our knowledge, this is
      only the second report describing primary oligoastrocytoma of the spinal cord.
      Genetic analysis may provide a clue in selecting optimal adjuvant therapies.

PMID- 14706388
TI  - Intracanalicular aneurysm at the meatal loop of the distal anterior inferior
      cerebellar artery: a case report and review of the literature.
AB  - BACKGROUND: Distal aneurysms of the anterior inferior cerebellar artery (AICA)
      are rare. Most of the reported cases have been located near the internal auditory
      meatus. Among these cases, only six located in the internal auditory meatus have
      been reported in the literature. METHODS: A 64-year-old female presented with
      sudden onset of severe headache. Computed tomography (CT) revealed moderate
      subarachnoid hemorrhage and Gd-DTPA enhanced magnetic resonance imaging (MRI)
      showed a small high-intensity mass at the right cerebellopontine angle. Although
      initial digital subtraction angiography (DSA) showed no vascular abnormalities,
      repeated DSA disclosed a saccular aneurysm at the top of the meatal loop of the
      right AICA. The patient underwent a suboccipital craniectomy on the 18th day
      after the hemorrhage RESULTS: . In this case, the aneurysm was completely buried
      in the internal auditory meatus. After unroofing the meatus, the aneurysm was
      successfully clipped. After 3 months of hospitalization, the patient was
      discharged with right-sided deafness, partial facial palsy, and no other
      complications. CONCLUSIONS: We discuss some of the clinical features and pitfalls
      in the surgical management of intracanalicular AICA aneurysms and review previous
      reports of similar cases.

PMID- 14706391
TI  - Trauma-induced ascending pharyngeal artery-internal jugular vein fistula: case
      report.
AB  - BACKGROUND: Ascending pharyngeal artery-internal jugular vein fistulas are rare.
      Only 2 spontaneous cases and one complicated neck surgery have been reported. We
      describe a trauma-induced case. CASE DESCRIPTION: A 31-year-old man presented
      left-sided tinnitus and a pulsating bruit for 5 months after head trauma.
      Cerebral angiography demonstrated a fistula between the left ascending pharyngeal
      artery and left internal jugular vein. Embolization of the fistula was performed
      using platinum fibrous microcoils. CONCLUSIONS: This case and a review of the
      literature illustrate the causes, manifestations, image studies, and treatment
      for a fistula between the ascending pharyngeal artery and internal jugular vein.

PMID- 14706393
TI  - Thrombosis of a spinal arteriovenous malformation after hemorrhage: case report.
AB  - BACKGROUND: Thrombosis of cerebral arteriovenous malformations (AVM) and spinal
      dural arteriovenous fistulas following hemorrhage rarely have been reported.
      Rarer still is thrombosis of spinal AVMs following hemorrhage. CASE DESCRIPTION:
      A 6-year-old boy presented with sudden low back and sciatic pain, bilateral leg
      weakness, and an intramedullary spinal cord hematoma. Spinal angiography
      demonstrated dilated feeding arteries without shunting, and no intervention was
      performed. Over time, these enlarged arteries reduced in caliber, and the patient
      recovered fully. CONCLUSIONS: The rarity of spinal AVMs and AVM thrombosis make
      their coincidence in this case unique. Although surgical intervention would have
      enabled definitive diagnosis of the spinal AVM, it is not mandatory in the
      absence of arteriovenous shunting. What is mandatory, however, is continued
      angiographic surveillance, particularly in pediatric patients.

PMID- 14706394
TI  - Cerebral vein thrombosis associated with aneurysmal subarachnoid bleeding:
      implications for treatment.
AB  - BACKGROUND: Cerebral vein thrombosis associated with aneurysmal subarachnoid
      bleeding is an uncommon event rarely described in the literature. We report here
      a case and summarize the problems in the management of this patient. CASE
      DESCRIPTION: A 48-year-old female suffered from two episodes of severe headache
      and vomiting 7 days before and on the day of admission. She was deeply somnolent
      with mild paresis of her right leg. Computed tomography (CT) scans revealed
      diffuse basal subarachnoid bleeding and a left parietal subcortical hemorrhagic
      area. A cerebral angiogram demonstrated an anterior communicating artery
      aneurysm. The angiographic late venous phase showed nonopacification of the
      cortical veins on the hemorrhagic area compatible with cerebral vein thrombosis.
      She underwent successful aneurysm clipping combined with moderate systemic
      anticoagulation. After 7 days of gradual clinical improvement she presented acute
      bilateral cerebral herniation signs and died 48 hours later. CT scan showed a
      generalized brain swelling. Postmortem examination confirmed the correct
      occlusion of the ruptured aneurysm sac and the presence of a postthrombotic
      subcortical left parietal hemorrhage as well as a complete obstruction of the
      superior sagittal sinus extended into both transverse sinus. CONCLUSIONS: The
      fatal outcome with the documented extended thrombosis, despite careful
      anticoagulation therapy, indicates the necessity of closely meshed follow-up
      studies examining the sinus patency in such complicated cases with associated
      pathology.

PMID- 14706396
TI  - "I went through it, so they should go through it!". Academia or academentia? How
      will we certify competence throughout a physician's career?

PMID- 14706399
TI  - Learning to drive.

PMID- 14706400
TI  - Importance of routine health checkups in young adults.

PMID- 14706401
TI  - Behavioral interventions to reduce incidence of HIV, STD, and pregnancy among
      adolescents: a decade in review.
AB  - PURPOSE: To review adolescent sexual risk-reduction programs that were evaluated
      using quasi-experimental or experimental methods and published in the 1990s. We
      describe evaluated programs and identify program and evaluation issues for health
      educators and researchers. METHODS: We systematically searched seven electronic
      databases and hand-searched journals to identify evaluations of behavioral
      interventions to reduce sexual risk behaviors among adolescents. Articles were
      included if they were published in the 1990s, provided a theoretical basis for
      the program, information about the interventions, clear aims, and quasi
      experimental or experimental evaluation methods. We identified 101 articles, and
      24 met our criteria for inclusion. RESULTS: We reviewed these evaluations to
      assess their research and program characteristics. The majority of studies
      included randomized controlled designs and employed delayed follow-up measures.
      The most commonly measured outcomes were delay of initiation of sexual
      intercourse, condom use, contraceptive use, and frequency of sexual intercourse.
      Programs ranged from 1 to 80 sessions, most had adult facilitators, and commonly
      included skills-building activities about sexual communication, decision-making,
      and problem solving. The programs included a wide range of strategies for content
      delivery such as arts and crafts, school councils, and community service
      learning. CONCLUSIONS: Analysis of these programs suggest four overall factors
      that may impact program effectiveness including the extent to which programs
      focus on specific skills for reducing sexual risk behaviors; program duration and
      intensity; what constitutes the content of a total evaluated program including
      researchers' assumptions of participants' exposure to prior and concurrent
      programs; and what kind of training is available for facilitators.

PMID- 14706402
TI  - Development of a growth hormone injection questionnaire for adolescents.
AB  - We developed an instrument to assess feelings about self-injection of growth
      hormone (GH) in adolescents with growth disorders. Summary scores did not differ
      significantly by cohort, age, gender, or diagnosis. Adolescents who were more
      comfortable with GH injections had higher health-related quality of life,
      functional capacity, and self-control.

PMID- 14706403
TI  - Primary care providers' willingness to see unaccompanied adolescents.
AB  - PURPOSE: To describe primary care practitioners' office policies and willingness
      to provide medical care for unaccompanied adolescents aged 11-17 years. METHODS:
      A unique 32-item survey was mailed in June and July, 2001 to 1979 office-based
      pediatricians and family practitioners randomly selected from the American
      Medical Association's physician database. The survey included questions regarding
      demographic information, number of adolescents seen in the practice, office
      policies regarding adolescents alone in the clinic, and 5-point Likert scales
      regarding their willingness to see patients in various situations, as well as to
      see patients in 12 brief clinical scenarios. Predictors of the willingness to see
      adolescents alone were identified and entered into binomial logistic regression
      models. Specific policies included on the surveys were coded into groups.
      RESULTS: Survey responses (n = 710) represented a 36% response rate. This sample
      included 288 family practitioners and 368 pediatricians; 43.3% of physicians
      reported having a specific policy regarding seeing adolescents without their
      parents present. Family practitioners were more likely than pediatricians to
      report having such a policy (51.3% vs. 38.2%, p =.001,), yet pediatricians
      reported a higher percentage of adolescents in their practices than family
      practitioners (22.6% vs. 12.4%, p <.0005). Not having a policy was an independent
      predictor of "often" or "always" seeing an adolescent alone for routine health
      maintenance (OR = 2.84, 95% CI 1.91-4.24) and urgent care visits (OR = 3.01, 95%
      CI 1.90-4.77). Specific policies varied, and many physicians assessed each case
      on an individual basis. CONCLUSIONS: Specific policies are associated with a
      decreased willingness of physicians to see adolescents who are unaccompanied by a
      parent. Carefully developed clinic policies that are consistent with legal
      guidelines should be implemented in order to maximize adolescents' abilities to
      access care.

PMID- 14706404
TI  - Generic health-related quality of life instruments in children and adolescents: a
      qualitative analysis of content.
AB  - PURPOSE: To determine the extent of differences and similarities in content
      between heath-related quality of life (HRQOL) instruments for children and
      adolescents. METHODS: A descriptive and explanatory qualitative approach was
      carried out. Instruments specifically designed for use with children or
      adolescents were included. To assure the validity of the findings a triangulation
      of the analysis and "member checking" were performed. RESULTS: Ten questionnaires
      were analyzed. All of them included items referring to physical, psychological,
      and social aspects of health. A relatively low number of categories explained the
      content of the questionnaires. CONCLUSIONS: A reasonably coherent notion of HRQOL
      underlies instruments available for children and adolescents. HRQOL measurement
      in young people is still in its developmental step.

PMID- 14706405
TI  - Emotional intelligence and smoking risk factors in adolescents: interactions on
      smoking intentions.
AB  - PURPOSE: To examine interactions between emotional intelligence (EI) and smoking
      risk factors on smoking intentions in adolescents. METHODS: EI ios defined as the
      ability to: accurately perceive, appraise, and express emotion; access and/or
      generate feelings in facilitating thought; understand emotion and emotional
      knowledge; and regulate emotions. EI of 416 6th graders (53% girls) from middle
      schools in the Los Angeles area (mean age = 11.3 years; 32% Latino, 29%
      Asian/Pacific Islander, 13% white, 19% Multiethnic, 6% Other) was assessed with
      an abbreviated version of the Multifactor Emotional Intelligence Scale,
      Adolescent Version (MEIS). This was a competence-based measure assessing an
      individual's ability to perceive, understand, and manage emotion. Logistic
      regression models were fit to test interactions between EI and ever trying
      cigarettes, hostility, and perceived ability to refuse a cigarette from someone
      just met, on intentions to smoke in the next year. RESULTS: High EI adolescents
      were more likely to intend to smoke in the next year if they had previously
      experimented with smoking. Those with low EI were more likely to intend to smoke
      if their perceived ability to refuse a cigarette offer from a person they just
      met was low or hostility level was high. CONCLUSIONS: These preliminary results
      indicate that EI interacts with risk factors to reduce smoking intentions, and
      contributes evidence to a link between EI and smoking in adolescents.

PMID- 14706406
TI  - Children and adolescents' choices of foods and beverages high in added sugars are
      associated with intakes of key nutrients and food groups.
AB  - PURPOSE: To determine associations between intakes of the primary food and
      beverage sources of added sugars and intakes of key nutrients and food pyramid
      groups among U.S. children aged 6-17 years. METHODS: The 1994-96 and 1998 U.S.
      Department of Agriculture (USDA) Continuing Survey of Food Intakes by Individuals
      (CSFII) were used to examine the diets of U.S. children aged 6-17 years, who
      provided 2 full days of dietary data. The nationally representative sample (n =
      3038) included children age 6-11 (n = 1913) and adolescents age 12-17 (n = 1125).
      Food codes for sweetened foods and beverages were selected from the USDA Food
      Coding Scheme and categorized into five food and beverage categories. The
      Statistical Analysis System software program was used to recode and format the
      data for statistical analysis and the Survey Data Analysis System was used to
      apply sample weights and generate statistical procedures. RESULTS: The
      consumption of sweetened dairy products was positively associated with calcium
      intakes for children and adolescents. Consumption of presweetened cereals
      increased the likelihood of the children and adolescents meeting recommendations
      for the essential shortfall micronutrients calcium, folate, and iron, whereas the
      consumption of sugar-sweetened beverages, sugars and sweets, and sweetened grains
      decreased the likelihood of meeting the Dietary Reference Intakes (DRI) for these
      nutrients. Only children who were nonconsumers of sugar-sweetened beverages had a
      mean calcium intake that met the adequate intakes (AI). Consumption of sweetened
      dairy products and presweetened cereals was positively associated with the number
      of dairy servings consumed per day for both age groups. CONCLUSIONS: On average,
      consumption of sweetened dairy foods and beverages and presweetened cereals had a
      positive impact on children and adolescents' diet quality, whereas sugar
      sweetened beverages, sugars and sweets, and sweetened grains had a negative
      impact on their diet quality.

PMID- 14706407
TI  - Violence perpetration across peer and partner relationships: co-occurrence and
      longitudinal patterns among adolescents.
AB  - PURPOSE: To examine the co-occurrence and consistency over time of peer violence,
      sexual aggression, and dating violence among European American and Mexican
      American adolescent boys and girls. METHODS: One-hundred-twelve girls and 135
      boys who were either European American or Mexican-American were recruited from a
      large health maintenance organization. They were interviewed by telephone at
      baseline (at ages 16 to 20 years) and at one-year follow-up. Variable-centered
      and person-centered analyses examined the co-occurrence of violent behavior
      across domains, and whether adolescents who engaged in violent behavior at
      baseline also engaged in violent behavior during the following year. RESULTS:
      Results indicated that adolescent boys who engaged in violence in one domain were
      more likely to engage in violence in other domains during the same time period.
      Results for girls were less consistent. For boys but not girls, perpetration of
      either sexual aggression or peer violence was a significant predictor of the same
      behavior at follow-up. Person-centered analyses indicated that boys who
      perpetrated both peer violence and sexual aggression at baseline were most likely
      to perpetrate later violence. CONCLUSIONS: These results suggest that adolescent
      boys who engage in peer violence are also at risk for perpetrating sexual
      aggression or dating violence. Boys who perpetrate peer violence and sexual
      aggression are at high risk for later violence. Interventions with a dual focus
      on peer and partner violence may be valuable.

PMID- 14706408
TI  - The intention of adolescents to carry a knife or a gun: a study of low-income
      African-American adolescents.
AB  - PURPOSE: To examine whether African-American inner-city adolescents are
      independently motivated by a fear of victimization or by delinquency to carry a
      knife or gun. METHODS: A household sample of 130 female and 93 male African
      American adolescents, aged 13-19 years old, were queried about their fear of
      victimization, history of delinquency, and intention to carry a knife or a gun in
      the next 3 months. RESULTS: A high intention to carry a knife was reported by 27%
      of the males and 35% of the females. A high intention to carry a gun was reported
      by 25% of the males and 9% of the females. The intention to carry a knife was
      independently associated with a history of delinquency in females (odds ratio
      [OR] = 3.0; 95% confidence interval [CI] = 1.4-6.2) and males (OR = 4.7; 95% CI =
      1.7-13.3). It was not associated with a fear of victimization. The intention to
      carry a gun was independently associated with fear of victimization in females
      (OR = 4.5; 95% CI = 1.1-17.7) and males (OR = 3.3; 95% CI = 1.1-9.9). It was also
      independently associated with a history of delinquency in females (OR = 4.1; 95%
      CI = 1.1-16.3) and males (OR = 11.7; 95% CI = 3.1-44.7). CONCLUSIONS: Delinquency
      may play a role in motivating inner-city African-American adolescents to carry a
      knife, whereas both delinquency and fear of victimization may influence
      adolescents' motivation to carry a gun.

PMID- 14706409
TI  - Why is work intensity associated with heavy alcohol use among adolescents?
AB  - PURPOSE: To examine and explain the relationship between work intensity (number
      of hours worked per week) and heavy alcohol use among adolescents. METHODS:
      Analyses were conducted with two waves of in-home interview data provided by a
      representative sample of adolescents who participated in the National
      Longitudinal Study of Adolescent Health. Multinomial logistic regression analyses
      were conducted to determine whether a higher level of work intensity at Wave 1
      predicted a higher level of past-year heavy drinking approximately 1 year later
      at Wave 2, and the degree to which the relationship between work intensity and
      heavy drinking persisted after adjusting for demographic characteristics, alcohol
      use before Wave 1, and psychosocial risk and protective factors in family,
      school, and peer-individual domains. RESULTS: Higher levels of work intensity at
      Wave 1 (11-20 or more than 20 hours/week) were predictive of heavy drinking at
      Wave 2. However, these effects were substantially attenuated after adjusting for
      demographic characteristics and prior alcohol use. Risk and protective factors
      such as school commitment, friends' drinking, and delinquency also partially
      explained the effects of work intensity and background variables on heavy
      drinking, suggesting that these factors may act as confounders and/or mediators.
      CONCLUSIONS: This study suggests that working more than 10 h/week increases the
      likelihood of heavy alcohol use among adolescents, and that the effect of work
      intensity is largely, but not completely attributable to demographic
      characteristics (e.g., age, race/ethnicity, personal income), prior alcohol use,
      and family, school, and peer-individual factors.

PMID- 14706410
TI  - Alcohol use and abuse by adolescents: the impact of living in a border community.
AB  - PURPOSE: To determine the rates of alcohol consumption and alcohol-related risk
      behaviors among a sample of high school students living on the U.S.-Mexico
      border, as well as to investigate factors associated with alcohol use among this
      population. METHODS: A self-administered anonymous questionnaire was administered
      to students in grades 9-12 during Fall and Spring semesters of 2001 (n = 1366;
      639 males and 722 females) in 16 high schools in a community along the U.S.
      Mexico border. The questionnaire addressed demographic factors, alcohol
      consumption, and alcohol-related behaviors. Surveys were completed by Chi-square
      tests for homogeneity of the odds ratio and logistic regression models were used
      to identify factors significantly associated with the outcome variables. RESULTS:
      Rates of binge drinking (45%), drinking and driving (19%), and riding with a
      driver who had been drinking (46%) were higher for our study population when
      compared with state and national rates. Students who consumed alcohol were more
      likely to report alcohol-related problems and lower academic grades. Drinking
      while in Mexico was significantly associated with binge drinking (OR = 6.44),
      drinking and driving (OR = 5.39), and riding with a driver who has been drinking
      (OR = 3.12). CONCLUSIONS: The high rates of alcohol risk behaviors among students
      living on the U.S.-Mexico border underscore the need to develop and implement
      culturally appropriate prevention programs that address alcohol consumption in
      Mexico, particularly in terms of students driving back home.

PMID- 14706411
TI  - Glue sniffing polyneuropathy: an under recognized aspect of a public health
      hazard.

PMID- 14706412
TI  - Access to health care among Australian adolescents young people's perspectives
      and their sociodemographic distribution.
AB  - PURPOSE: To identify the health concerns for which adolescent residents in New
      South Wales, Australia, do not receive health care, and the associated factors,
      including their sociodemographic distribution. METHODS: Purposive sampling was
      used to recruit school students who were stratified by gender and age (12-14, 14
      16 and 16-17 years), from schools stratified by socioeconomic status and
      urban/rural location. Out-of-school young people were recruited through youth
      health services. Qualitative methods were used to collect and analyze data.
      RESULTS: Eighty-one focus groups were conducted. Most young people defined health
      solely in terms of their physical well-being, but still identified a broad range
      of situations, conditions, or behaviors which they believed might affect their
      health. One-third of females and two-thirds of males said they would not seek
      help for their health concerns, and when they did, were most likely to seek help
      from family, friends, or others they trusted. When professional help was sought,
      young people again preferred someone they knew and trusted. The three groups of
      barriers to accessing health care were: concerns about confidentiality, knowledge
      of services and discomfort in disclosing health concerns, and accessibility and
      characteristics of services. Factors related to use of health care services were
      associated with age, gender, and location, but rarely with socioeconomic status.
      CONCLUSIONS: The majority of these young people in New South Wales (particularly
      males) do not seek health care despite identifying a broad range of issues that
      affect their health.

PMID- 14706413
TI  - 25th anniversary: an editor's glance in the rear view mirror.

PMID- 14706414
TI  - Asthma and mental disorders in primary care.
AB  - This study examines relationships between asthma and likelihood of current mental
      disorders and suicidal ideation in an urban primary care population. A systematic
      waiting room sample of 998 adult patients was screened for mental disorders using
      the PRIME-MD PHQ. Asthma diagnoses were provided by primary care physicians.
      Multivariate logistic regression analyses were used to determine the odds of
      current major depression, panic attacks, generalized anxiety disorder, alcohol
      and drug use disorder, and suicidal ideation among patients with a diagnosis of
      asthma, as compared to those without asthma. After controlling for differences in
      sociodemographic characteristics and comorbid mental disorders, asthma was
      associated with increased likelihood of panic attack (OR=1.7 (1.1, 2.6)) and
      suicidal ideation (OR=1.9 (1.03, 3.4)). There was no statistically significant
      association between asthma and major depression, generalized anxiety disorder,
      alcohol, or drug use disorders after adjustment. Results suggest that physician
      diagnosed asthma is associated with self-reported panic attacks and suicidal
      ideation in a systematic sample of primary care patients. Physicians who treat
      patients with asthma should remain vigilant for the presence of comorbid
      psychiatric problems and carefully evaluate whether there is a clinical need to
      treat each condition.

PMID- 14706416
TI  - The acceptability of psychotropic vs. other medications among a small urban
      primary care sample.
AB  - In a small urban sample of primary care patients, this pilot study was designed
      to explore attitudes toward various types of medications, comparing psychotropic
      vs. non-psychotropic types. Sixty-two participants (77% female, 66% African
      American) completed a two-page survey developed by the authors. Participants were
      asked "How acceptable would it be to you if a doctor prescribed the following
      medications?" For analyses, the 12 medications were divided into 3 categories: 1)
      psychotropic; 2) mixed (medications that could be categorized as either
      psychotropic or not); and 3) nonpsychotropic. Results indicated that participants
      rated psychotropic medications as less acceptable than nonpsychotropic
      medications, which in one of the analyses was more pronounced among female
      participants. The possible implications of these findings are discussed.

PMID- 14706415
TI  - Psychiatric considerations in the patient receiving organ transplantation: a
      clinical case conference.
AB  - Psychiatric consultations to evaluate a patient's suitability to receive organ
      transplantation can require the integration of multiple types and sources of
      information. A patient's social support network, history of treatment compliance,
      ongoing Axis I and Axis II disorders, and understanding of the procedure and
      follow-up required must all be evaluated during such a consultation. This article
      presents the case of a woman with borderline personality disorder who developed
      hepatic failure following a drug overdose, and discusses her evaluation for liver
      transplantation. The discussion frames the pertinent issues in the transplant
      evaluation and describes the perioperative (transplant) management of the
      borderline patient.

PMID- 14706417
TI  - Anti- and pro-inflammatory considerations in antidepressant use during medical
      illness: bupropion lowers and mirtazapine increases circulating tumor necrosis
      factor-alpha levels.

PMID- 14706418
TI  - Mirtazapine for the treatment of interferon-induced psychopathology.

PMID- 14706419
TI  - Association of depression with medical illness: does cortisol play a role?
AB  - Elevated cortisol in a subset of depressed patients is an enduring and well
      replicated finding. Much interest has focused on the possible effects of
      depression on the hippocampus; however, an emerging body of evidence suggests an
      association between depression and non-central nervous system illnesses. In this
      review, data on the effects of depression on the brain and other organ systems
      sensitive to elevated cortisol are discussed. From searches of the MEDLINE,
      PSYCHINFO, and Current Contents databases, and other sources, articles were found
      specifically related to depression and physical changes or medical conditions
      associated with corticosteroid excess in patients with Cushing's disease,
      including cognitive impairment, hippocampal atrophy, increased waist-to-hip
      ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data
      are strongest for a relationship between elevated cortisol and depression,
      hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone
      density. Some evidence suggests an association between depression and
      hypertension, peptic ulcers, and diabetes. Depression does not appear to be
      associated with hyperlipidemia. The data provide some support for similar health
      effects in depressed patients and patients with Cushing's disease or the
      metabolic syndrome; however, additional studies are needed relating systemic
      effects of depression to cortisol. Limitations of the current literature,
      treatment implications, and possible directions for future research are
      discussed.

PMID- 14706420
TI  - Pituitary-adrenal responses to standard and low-dose dexamethasone suppression
      tests in adult survivors of child abuse.
AB  - BACKGROUND: Previous studies indicate that adverse childhood events are
      associated with persistent changes in corticotropin-releasing factor neuronal
      systems. Our aim was to determine whether altered glucocorticoid feedback
      mediates the neuroendocrine sequelae of childhood trauma. METHODS: Standard and
      low-dose dexamethasone suppression tests (DST) were performed in women with a
      history of child abuse (n=19), child abuse and major depression (n=16), major
      depression and no childhood trauma (n=10), and no history of mental illness or
      childhood trauma (n=19). Secondary analysis with posttraumatic stress disorder
      (PTSD) as the organizing diagnosis was also conducted. RESULTS: In the low-dose
      DST, depressed women with a history of abuse exhibited greater cortisol
      suppression than any comparator group and greater corticotropin suppression than
      healthy volunteers or nondepressed abuse survivors. There were no differences
      between nondepressed abuse survivors and healthy volunteers in the low-dose DST
      or between any subject groups in the standard DST. The PTSD analysis produced
      similar results. CONCLUSIONS: Cortisol supersuppression is evident in
      psychiatrically ill trauma survivors, but not in nondepressed abuse survivors,
      indicating that enhanced glucocorticoid feedback is not an invariable consequence
      of childhood trauma but is more related to the resultant psychiatric illness in
      traumatized individuals.

PMID- 14706421
TI  - Physical and sexual abuse, salivary cortisol, and neurologic correlates of
      violent criminal behavior in female prison inmates.
AB  - BACKGROUND: Both physical and emotional traumas have been related to neurologic
      and neuroendocrine abnormalities that may be associated with violent behavior.
      METHODS: A modified case-control design was used for blinded comparison of 113
      female inmates convicted of violent and nonviolent crimes. History of having been
      physically or sexually abused, neurologic history and physical examination, basal
      salivary cortisol levels, and associated variables were investigated to identify
      possible risk factors for violent compared to nonviolent criminal convictions.
      RESULTS: Of all inmates studied, 95% had neurologic histories predating the
      current crime and/or neurologic examination abnormalities. Logistic regression
      revealed morning cortisol levels, number of years since last abuse, number of
      prior suicide attempts, and traumatic brain injuries with loss of consciousness
      to be significantly associated with current violent convictions, with a mean of
      two brain injuries with loss of consciousness per subject in the violent group.
      CONCLUSIONS: A greater number of traumatic brain injuries with loss of
      consciousness and suicide attempts, more recent abuse, and low morning basal
      salivary cortisol levels could be associated with dangerous violent criminal
      behavior, including murder, in female prison inmates. Future research should
      investigate neuroendocrine challenges, more psychiatric and violence measures,
      and different populations with longitudinal designs.

PMID- 14706422
TI  - Neuropsychological performance in pediatric bipolar disorder.
AB  - BACKGROUND: Growing awareness of childhood bipolar disorder necessitates further
      cognitive neuroscience research to determine unique developmental differences
      between pediatric and adult onset bipolar disorder. We sought to examine whether
      neuropsychological function in children with bipolar disorder resembles that in
      adults with the illness and to extend our knowledge about cognitive function in
      pediatric bipolar disorder. METHODS: We administered a computerized
      neuropsychological test battery known as the Cambridge Neuropsychological Test
      Automated Battery to a sample of 21 children and adolescents with bipolar
      disorder and compared them with 21 age- and gender-matched controls. RESULTS: In
      comparison to controls, children with bipolar disorder were impaired on measures
      of attentional set-shifting and visuospatial memory. Post hoc analyses in
      pediatric bipolar disorder subjects did not show significant associations between
      neuropsychological performance and manic symptomatology or attention
      deficit/hyperactivity disorder comorbidity. CONCLUSIONS: Cambridge
      Neuropsychological Test Automated Battery data presented here in pediatric
      bipolar disorder fit well within the broader framework of known neurocognitive
      deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects
      demonstrated selective deficiencies in attentional set-shifting and visuospatial
      memory. Our work suggests altered ventrolateral prefrontal cortex function,
      especially when linked to other lesion and neuroimaging studies.

PMID- 14706423
TI  - Possible association between a haplotype of the GABA-A receptor alpha 1 subunit
      gene (GABRA1) and mood disorders.
AB  - BACKGROUND: The gamma-aminobutyric acid (GABA) neurotransmitter system has been
      implicated in the pathogenesis of mood disorders. The GABRA1 gene encodes one of
      the subunits of GABA-A receptor and is located on human chromosome 5q34-q35,
      which is a region reportedly linked to mood disorders. We examined the GABRA1
      gene as a candidate for mood disorders. METHODS: We performed mutation screening
      of GABRA1 in 24 Japanese bipolar patients and evaluated associations in Japanese
      case-control subjects consisting of 125 patients with bipolar disorder, 147
      patients with depressive disorders, and 191 healthy control subjects.
      Associations were confirmed in the National Institute of Mental Health (NIMH)
      Initiative Bipolar Pedigrees, which consists of 88 multiplex pedigrees with 480
      informative persons. RESULTS: We identified 13 polymorphisms in the GABRA1 gene.
      Nonsynonymous mutations were not found. Association of a specific haplotype with
      affective disorders was suggested in the Japanese case-control population
      (corrected p=.0008). This haplotype association was confirmed in the NIMH
      pedigrees (p=.007). CONCLUSIONS: These results indicate that the GABRA1 gene may
      play a role in the etiology of bipolar disorders.

PMID- 14706424
TI  - Serotonin transporter gene may be involved in short-term risk of subsequent
      suicide attempts.
AB  - BACKGROUND: In the first year following a suicide attempt, patients are at high
      risk for reattempt and for completed suicide. We aim to determine the predictive
      value of two serotonin-related genes, the tryptophan hydroxylase (TPH) and
      serotonin transporter (5-HTTLPR) genes that have been involved in the
      susceptibility to suicidal behavior. METHODS: After a one-year follow-up study of
      103 patients hospitalized after a suicide attempt, patients have been genotyped
      for both the A218C TPH and the functional S/L 5-HTTLPR polymorphisms. RESULTS:
      Patients who reattempted suicide during the follow-up period had significantly
      higher frequencies of the S allele and the SS genotype. The odds ratio for the SS
      genotype vs. the LL genotype was 6.5 (95% CI [1.18-35.84]). No difference was
      observed for TPH gene. Patients carrying the SS genotype were more impulsive.
      However, multivariate analysis suggested an independent effect of both the SS
      genotype and impulsivity on the risk of repeated suicide attempts. CONCLUSIONS:
      These results suggest that the 5-HTTLPR SS genotype is associated with further
      suicide attempts among patients who have previously attempted suicide.

PMID- 14706425
TI  - Brain-derived neurotrophic factor rescues neuronal death induced by
      methamphetamine.
AB  - BACKGROUND: Methamphetamine (MA) induces degeneration of various regions of the
      brain, resulting in neuropsychiatric damage. Although the underlying mechanisms
      of MA-induced neurotoxicity have been studied, there are few reports to date
      regarding the factor(s) that can effectively prevent MA-induced neurotoxicity.
      Because brain-derived neurotrophic factor (BDNF) has been known to prevent many
      kinds of neuronal cell death, we investigated whether BDNF inhibits MA-induced
      neuronal death. METHODS: Using primary cortical neurons, we examined the effect
      of BDNF on MA-induced neuronal death. In addition, using pharmacologic and
      molecular biological tools, we elucidated which pathways are involved in this
      effect. RESULTS: Brain-derived neurotrophic factor dose-dependently blocked MA
      induced neuronal death, and this effect was inhibited by phosphatidylinositol-3
      kinase inhibitors. In addition, overexpression of activated Akt protects neurons
      against MA. Furthermore, expression of kinase-defective Akt blocked the effect of
      BDNF on MA-induced neuronal death. CONCLUSIONS: Brain-derived neurotrophic factor
      effectively blocks MA-induced neuronal death, and Akt activation is necessary and
      sufficient for this effect.

PMID- 14706426
TI  - Detecting pediatric autoimmune neuropsychiatric disorders associated with
      streptococcus in children with obsessive-compulsive disorder and tics.
AB  - BACKGROUND: A subgroup of children with obsessive-compulsive and tic disorders
      are proposed to have an infectious trigger. The purpose of this study was to
      investigate the relationship between group A streptococcal titers and symptom
      fluctuations in children with a clinical course resembling that described for
      pediatric autoimmune neuropsychiatric disorders associated with streptococcus.
      METHODS: Twenty-five children with obsessive-compulsive disorder and/or tic
      disorder were evaluated for neuropsychiatric severity and group A streptococcal
      antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6
      week intervals for > or = six consecutive evaluations (total visits=277).
      RESULTS: Children with large symptom fluctuations (n=15) were compared with
      children without dramatic fluctuations (n=10). Co-movements of obsessive
      compulsive/tic severity and group A streptococcal antibodies were assessed. In
      subjects with large symptom changes, positive correlations were found between
      streptococcal titers and obsessive-compulsive severity rating changes (p=.0130).
      These subjects were also more likely to have elevated group A streptococcal
      titers during the majority of observations (p=.001). Tic symptom exacerbations
      occurred more often in the fall/winter months than spring/summer months (p=.03).
      CONCLUSIONS: Patients with marked obsessive-compulsive/tic symptom changes may be
      characterized by streptococcal titer elevations and exhibit evidence of seasonal
      tic exacerbations.

PMID- 14706427
TI  - Psychiatric disorders and stages of smoking.
AB  - BACKGROUND: We examined the role of DSM-III-R psychiatric disorders in predicting
      the subsequent onset of daily smoking, smokers' progression to nicotine
      dependence, and the persistence of smoking. METHODS: The Tobacco Supplement of
      the National Comorbidity Survey was administered to a representative subsample of
      4414 persons 15-54 years of age. DSM-III-R psychiatric disorders and information
      on age of onset of psychiatric disorders, daily smoking, and smoking cessation
      were ascertained with the World Health Organization's Composite International
      Diagnostic Interview. RESULTS: Preexisting psychiatric disorders that have not
      remitted (i.e., active disorders) predicted an increased risk for the first onset
      of daily smoking and for smokers' progression to nicotine dependence. The
      increased risk applied across most of the disorders examined in the study,
      including major depression, anxiety disorders, and substance use disorders.
      Persons with four or more active disorders were at higher risk for daily smoking
      (2.1 vs. 1.4) and for nicotine dependence (2.9 vs. 1.4) than were persons with
      one active disorder. With few exceptions, remitted (i.e., past) disorders did not
      predict the subsequent onset of daily smoking. Preexisting psychiatric disorders
      did not influence smokers' potential for quitting; the persistence of smoking in
      the year preceding the interview was unrelated to history of psychiatric
      disorders. CONCLUSIONS: The results suggest the possibility of additional and
      previously unrecognized public health benefits of early treatment of mental
      disorders, in that persons with various mental disorders whose illness had
      remitted were not at increased risk for daily smoking, in contrast with persons
      with active disorders.

PMID- 14706428
TI  - Differences between smokers and nonsmokers in regional gray matter volumes and
      densities.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) studies have demonstrated large
      scale brain abnormalities in cigarette smokers, such as ventricular enlargement
      and atrophy. Converging lines of evidence point to functional differences between
      smokers and nonsmokers in specific brain regions, namely the lateral prefrontal
      cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and thalamus.
      Using MRI, we examined these regions for differences in gray matter between
      smokers and nonsmokers. METHODS: Thirty-six otherwise healthy adults (19 smokers
      and 17 nonsmoking control subjects) underwent three-dimensional Fourier-transform
      spoiled-gradient-recalled acquisition MRI of the brain. Both hand-drawn regions
      of interest and the computer program voxel-based morphometry were used to assess
      group differences in regional gray matter volumes and densities, respectively.
      RESULTS: Smokers had smaller gray matter volumes and lower gray matter densities
      than nonsmokers in the PFC bilaterally, along with smaller volumes in the left
      dorsal ACC and lower gray matter densities in the right cerebellum. Smokers also
      had negative associations between pack-year smoking history and PFC gray matter
      densities. CONCLUSIONS: Smokers and nonsmokers differed in regional gray matter
      in brain areas previously linked with nicotine dependence. These findings might
      reflect effects of chronic smoking, predisposing traits that lead to smoking, or
      some combination of these factors.

PMID- 14706429
TI  - Functional polymorphisms in the sigma1 receptor gene associated with alcoholism.
AB  - BACKGROUND: Sigma1 receptors are involved in the pathogenesis of drug abuse. Two
      polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1)
      have been identified. To investigate the role of SIGMAR1 in conveying
      susceptibility to alcoholism, we performed a functional analysis of polymorphisms
      in the SIGMAR1 and a case-control study. METHODS: We initially screened for
      polymorphisms in the 5'-upstream region. The effects of the polymorphisms on
      transcriptional activity were determined using a gene reporter assay. The
      distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302
      control subjects. RESULTS: A novel T-485A polymorphism was identified. The
      transcriptional activity of the A-485 allele and the TT-241-240 allele was
      significantly reduced compared with that of the T-485 allele and the GC-241-240
      allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the
      TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p<.0001) were significantly higher
      in control subjects compared with alcoholic subjects. The T-485A and the GC-241
      240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2
      haplotype are possible protective factors for the development of alcoholism.

PMID- 14706431
TI  - Prepulse-elicited startle in prepulse inhibition.
AB  - BACKGROUND: Prepulse inhibition (PPI) has become a major experimental paradigm in
      the study of psychiatric disorders. In this study, a potential confound in
      measurement and interpretation of PPI, namely startle reactions to so-called
      "nonstartling" prepulses, was examined. METHODS: Prepulses of 80, 85, and 90
      dB(A) were presented on their own or followed by a pulse of 115 dB(A) (lead
      interval: 120 msec). RESULTS: Even at only 80 dB(A), prepulses presented alone
      elicited a response in about 50% of trials; and, except in the first stage of the
      experiment, responses became more frequent as prepulse intensity increased.
      Importantly, PPI at 80 and 85 dB(A) was negatively correlated with response
      probability to prepulses presented alone. CONCLUSIONS: Prepulses reliably
      activate the very startle system that they are thought to inhibit, and a high
      level of responsiveness to prepulses is associated with relatively lower levels
      of PPI. These findings might hold important implications for clinical and
      psychopharmacologic studies of PPI, and we suggest that the extent and influence
      of prepulse-elicited startles should be routinely examined.

PMID- 14706430
TI  - Platelet abnormalities associated with cerebral perfusion defects in cocaine
      dependence.
AB  - BACKGROUND: This study assessed whether reduced regional cerebral blood flow
      (rCBF; hypoperfusion) in cocaine-dependent (CD) patients is associated with
      platelet abnormalities and whether these platelet abnormalities predict
      improvement in hypoperfusion after 1 month of abstinence. METHODS: We correlated
      platelet number and aggregation with rCBF hypoperfusion in 54 CD patients at
      baseline and after a month of abstinence while taking either 325 mg aspirin or
      placebo. We measured rCBF by (SPECT) with (Tc-HMPAO). Platelet aggregation to
      adenosine diphosphate was compared at baseline and after treatment. RESULTS: At
      baseline the number of hypoperfused voxels positively correlated with higher
      platelet aggregation, and five brain regions (bilateral frontal, right insula,
      right cingulate, left temporal lobes) showed significantly more hypoperfusion in
      the high than low platelet aggregation group. After abstinence, hypoperfusion
      significantly improved regardless of treatment assignment, and greater platelet
      aggregation at baseline predicted greater improvement in hypoperfusion. After
      abstinence, only the cingulate continued to show more hypoperfusion in the high-
      than low-aggregation group. CONCLUSIONS: Because platelet function was related to
      hypoperfusion primarily in the distribution of the middle cerebral artery, where
      CD patients most commonly have strokes, more potent antiplatelet agents than
      aspirin might be effective.

PMID- 14706432
TI  - Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary-adrenal
      axis responses to naloxone: a preliminary report.
AB  - BACKGROUND: A common polymorphism in the catechol-O-methyltransferase gene
      involves a valine to methionine mutation that results in a threefold to fourfold
      decrease in enzyme activity. This polymorphism has been associated with altered
      mu-opioid receptor binding potential and prefrontal cognitive performance, as
      well as risk for several neuropsychiatric conditions. We hypothesized that
      subjects homozygous for the low-activity allele would have greater hypothalamic
      pituitary-adrenal axis responses to opioid blockade than subjects with the high
      activity allele. METHODS: Forty-six healthy adults were genotyped and underwent a
      procedure in which adrenocorticotropin hormone and cortisol responses to the
      opioid antagonist naloxone were examined. RESULTS: Findings showed that
      adrenocorticotropin hormone and cortisol responses were greater in subjects with
      the methionine/methionine genotype compared to subjects homozygous or
      heterozygous for the valine allele. CONCLUSIONS: These findings suggest that
      individual differences in catecholamine metabolism may impact hypothalamic
      pituitary-adrenal axis function and may play a pharmacogenetic role in responses
      to naloxone.

PMID- 14706433
TI  - Ethnicity, social class and hostility: effects on in vivo beta-adrenergic
      receptor responsiveness.
AB  - Little is known about the potential influences of social and psychosocial
      variables in accounting for ethnic differences in the beta-adrenergic receptor.
      We examined the effects of ethnicity, social class, and other variables on an in
      vivo marker of beta-adrenergic receptor responsiveness (Chronotropic 25 Dose,
      CD(25)) for 224 African-Americans and Caucasian-Americans. Social class was
      determined using the clinician-rated Hollingshead two-factor index. The Cook
      Medley hostility and Buss-Durkee assaultiveness subscales were administered to a
      subset of subjects. Results indicated that African-Americans had decreased beta
      receptor responsiveness compared to Caucasian-Americans after controlling for
      social class, age, and smoking (P=0.001). Secondary analysis for a subset of
      subjects revealed significant hostility x ethnicity interactions, such that
      hostility predicted decreased beta-receptor responsiveness for Caucasian
      Americans (P=0.004), but not for African-Americans. Thus, decreased beta
      adrenergic receptor responsiveness in African-Americans does not appear to be due
      to differences in current social class, age, or smoking status, nor to higher
      reports of hostility.

PMID- 14706434
TI  - Reactivity of immune, endocrine and cardiovascular parameters to active and
      passive acute stress.
AB  - This study clarified associations among immune, autonomic, and endocrine
      activities during mental arithmetic and cold pressor stress tasks in 26 women in
      the follicular phase. Both tasks decreased CD3+ T cells, CD4+ T cells, and CD19+
      B cells, whereas they increased lymphocytes, granulocytes, NK cells, and NK cell
      activity (NKCA). The mental arithmetic task had a greater impact than the cold
      pressor task on changes in CD3+ T cells and in NK cells. Cardiovascular
      reactivity to active stress was associated with increased NK cells and decreased
      CD3+ T cells. Reduced cortisol levels during passive stress were associated with
      decreased CD19+ B cells and with increased NK cells. The merits of this study are
      that it controlled the following factors. Perceived stress during the two tasks
      was matched; both tasks lasted long enough to elicit high-magnitude responses;
      and the length of the intervening rest period minimized probable carryover
      effects between tasks.

PMID- 14706435
TI  - Vital exhaustion, temperament, and cardiac reactivity in task-induced stress.
AB  - The associations between vital exhaustion (long-term stress), temperament, and
      cardiac reactivity were studied during an experimentally induced stress in a
      sample of 76 healthy subjects. Vital exhaustion was assessed with the Maastricht
      Questionnaire(MQ), and temperament with Cloninger's Temperament and Character
      Inventory (TCI). Cardiac reactivity was measured in terms of heart rate,
      respiratory sinus arrhythmia, and pre-ejection period. They were continuously
      measured during three stressors, i.e. mental arithmetic, reaction time, and
      giving speech. Results showed that vital exhaustion (long-term stress) was first
      of all associated with parasympathetic withdrawal. In addition, among exhausted
      persons the initial parasympathetic tone had no effect on task-induced
      parasympathetic reactivity, whereas in non-exhausted subjects parasympathetic
      reactivity was greatest when initial parasympathetic tone was high. Vital
      exhaustion interacted with temperament and gender: exhausted, persistent women
      expressed the highest level of physiological stress reactivity. Findings suggest
      that background stress may diminish one's capacity to cope with acute stress.

PMID- 14706436
TI  - Lack of effect of tryptophan depletion on the loudness dependency of auditory
      event related potentials in healthy volunteers.
AB  - It has previously been suggested that auditory event related potentials (AEPs)
      are a potential marker of central serotonergic (5-HT) activity in man, with the
      slope of the AEP amplitude stimulus intensity function (ASF-slope) inversely
      correlating with 5-HT activity. However, two recent studies investigating this
      hypothesis in healthy subjects by rapidly lowering central 5-HT concentrations
      using the acute tryptophan depletion paradigm have found no effect on ASF-slope
      [Biological Psychology, 59 (2002) 121; Psychopharmacology (Berl), 146 (1999)
      101]. These studies employed a 50g tryptophan depletion drink, which has been
      argued may not lower central 5-HT concentrations sufficiently. We here report the
      effect of tryptophan depletion on the AEP ASF-slope using 100g amino acid drinks
      with and without tryptophan in 14 healthy male subjects, employing a within
      subject, double blind, random, balanced order, cross-over design. No significant
      effect of tryptophan depletion was found on ASF-slope. These negative findings
      cast further doubt on the hypothesis that the ASF-slope is an indicator of
      central 5-HT function.

PMID- 14706437
TI  - Phasic heart rate responses to performance feedback in a time production task:
      effects of information versus valence.
AB  - This study examined the cardiac concomitants of feedback processing in a time
      production task derived from [Mittner et al., J. Cogn. Neurosci. 9 (1997) 788].
      Participants performed the time production task (i.e. 1-s intervals) under two
      conditions. In the experimental condition, feedback informed them that the
      produced interval was within or outside the acceptable range (too long or too
      short). In the other, yoked-control, condition feedback was unrelated to the
      actual estimate. The performance findings indicated that in the experimental
      condition, participants tended to adjust the new interval in the direction
      indicated by the feedback. In the control condition, however, the adjustments
      were largely unrelated to the information provided by the feedback. Heart rate
      slowed to feedback stimuli indicating that the estimate was outside the
      acceptable range. Surprisingly, cardiac slowing did not discriminate between
      experimental and control conditions. This finding seems to suggest that heart
      rate is sensitive to the valence rather than the information provided by the
      feedback. This finding is discussed vis-a-vis current neuroimaging and
      psychophysiological studies of performance monitoring.

PMID- 14706438
TI  - Effects of a small talking facial image on autonomic activity: the moderating
      influence of dispositional BIS and BAS sensitivities and emotions.
AB  - We examined the moderating influence of dispositional behavioral inhibition
      system and behavioral activation system (BAS) sensitivities, Negative Affect, and
      Positive Affect on the relationship between a small moving vs. static facial
      image and autonomic responses when viewing/listening to news messages read by a
      newscaster among 36 young adults. Autonomic parameters measured were respiratory
      sinus arrhythmia (RSA), low-frequency (LF) component of heart rate variability
      (HRV), electrodermal activity, and pulse transit time (PTT). The results showed
      that dispositional BAS sensitivity, particularly BAS Fun Seeking, and Negative
      Affect interacted with facial image motion in predicting autonomic nervous system
      activity. A moving facial image was related to lower RSA and LF component of HRV
      and shorter PTTs as compared to a static facial image among high BAS individuals.
      Even a small talking facial image may contribute to sustained attentional
      engagement among high BAS individuals, given that the BAS directs attention
      toward the positive cue and a moving social stimulus may act as a positive
      incentive for high BAS individuals.

PMID- 14706439
TI  - Advanced Drug Delivery Reviews: cornerstone in the stimulation and dissemination
      of innovative drug delivery research.

PMID- 14706440
TI  - Delivery of photosensitizers in photodynamic therapy.

PMID- 14706441
TI  - Delivery of photosensitizing agents.

PMID- 14706442
TI  - Polymeric micelles to deliver photosensitizers for photodynamic therapy.
AB  - Polymeric micelles are emerging as attractive drug delivery systems. Hydrophobic
      drugs including photosensitizers for photodynamic therapy can be covalently bound
      or physically entrapped in the core of the micelles and thus be systemically
      delivered to, for example, tumors using passive or active targeting strategies.
      Polymers used for photosensitizer encapsulation include pluronics, poly(ethylene
      glycol) (PEG)-lipid conjugates, and pH-sensitive poly(N-isopropylacrylamide)
      based micelles or polyion complex (PIC) micelles. This paper reviews the results
      obtained so far, including drug loading, biodistribution studies, and therapeutic
      efficiency. The pH-sensitive micelles appear to be promising candidates for
      photosensitizer delivery.

PMID- 14706443
TI  - Liposomes for photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an evolving modality for the treatment of
      superficial tumors. The technique utilizes photosensitizing agents that are able
      to photochemically eradicate malignant cells. With the aim of improving the
      tumoritropic behaviour of photosensitizers, liposomes are presently being used as
      carrier and delivery systems for PDT. This review covers the different liposomal
      strategies that are available to target photosensitizers to tumor tissue. In
      general, conventional liposomes carrying photosensitizers are not able to
      establish elevated tumor-to-normal tissue ratios, hampering their generalised use
      as tumoritropic carriers of photosensitizers. Conversely, liposomes with a
      specifically modified design, i.e. long-circulating and especially actively
      targeting liposomes, stand a better chance in becoming truly tumoritropic
      carriers of photosensitizers. Strategies that can be employed to trigger the
      release of photosensitizer molecules from the liposomes are also discussed. The
      examined topics are supplemented with examples of the latest developments in the
      field of photodynamic therapy.

PMID- 14706444
TI  - Photosensitizer-antibody conjugates for detection and therapy of cancer.
AB  - Photodynamic therapy (PDT) is a promising approach for the treatment of
      superficially localized tumors. A limitation, however, is the lack of selectivity
      of the photosensitizers, which can result in severe toxicity. In this overview,
      the possibilities for using monoclonal antibodies (MAbs) for selective delivery
      of photosensitizers to tumors, are discussed. This approach is called
      photoimmunotherapy (PIT). For PIT to be successful, sufficient amounts of
      sensitizer should be coupled to the MAb without altering its biological
      properties. A challenging aspect herein is the hydrophobicity of therapeutic
      photosensitizers. Options for direct and indirect coupling of photosensitizers to
      MAbs are evaluated, while pros and cons are indicated. Special attention is paid
      to the quality testing of photoimmunoconjugates, as this information is important
      for further optimization of PIT. Results obtained thus far with PIT in in vitro
      and in vivo model systems are discussed. Despite the encouraging progress made,
      showing the high selectivity of photoimmunoconjugates, PIT still awaits initial
      clinical evaluation.

PMID- 14706445
TI  - Targeted photodynamic therapy via receptor mediated delivery systems.
AB  - Targeted photodynamic therapy (PDT) offers the opportunity of enhancing
      photodynamic efficiency by directly targeting diseased cells and tissues. While
      antibody-conjugates have received the most attention, cellular transformations
      offer numerous other potent targets to exploit during the delivery of
      photosensitizers (PSs) for PDT. Alterations in receptor expression, increased
      levels of specific cell surface membrane lipids and proteins as well as changes
      in the cellular microenvironment all occur in diseased cells. Along with other
      biochemical and physiological changes that occur during diseased and malignant
      cell transformation, these factors have been utilized in order to improve the
      efficacy of PDT. Attempts have been made to either increase the uptake of the dye
      by the target cells and tissues or to improve subcellular localization so as to
      deliver the dye to photosensitive sites within the cells. This review discusses
      various PS bioconjugates that utilize these factors and summarizes the results
      obtained to date.

PMID- 14706446
TI  - Photodynamic therapy of skin cancer: controlled drug delivery of 5-ALA and its
      esters.
AB  - Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and
      pre-cancerous conditions in dermatology. 5-Aminolevulinic acid (5-ALA) and simple
      derivatives thereof are the principal compounds used for this purpose. For
      optimal efficacy, the drug must be released at an appropriate rate from the
      formulation and penetrate the skin, ideally to reach the target tissue at a
      sufficiently high concentration. Because ALA is a polar, zwitterionic compound,
      its formulation in conventional topical vehicles, and its inherently poor skin
      permeability, poses important challenges for the pharmaceutical scientist. The
      synthesis of more lipophilic (e.g. ester) prodrugs of ALA resolves, in part,
      these issues but then demands that questions, related to biotransformation back
      to the parent 5-ALA and to stability, be addressed. The objective of this review,
      therefore, is to evaluate the state-of-the-art and identify those areas in which
      additional research is necessary.

PMID- 14706447
TI  - Photochemical internalisation in drug and gene delivery.
AB  - This article reviews a novel technology, named photochemical internalisation
      (PCI), for light-induced delivery of genes, proteins and many other classes of
      therapeutic molecules. Degradation of macromolecules in endocytic vesicles after
      uptake by endocytosis is a major intracellular barrier for the therapeutic
      application of macromolecules having intracellular targets of action. PCI is
      based upon the light activation of a drug (a photosensitizer) specifically
      locating in the membrane of endocytic vesicle inducing the rupture of this
      membrane upon illumination. Thereby endocytosed molecules can be released to
      reach their target of action before being degraded in lysosomes. The fact that
      this effect is induced by illumination means that the biological activity of the
      molecules can be activated at specific sites in the body, simply by illuminating
      the relevant region. We have used the PCI strategy to obtain light-induced
      delivery of a variety of molecules, including proteins, peptides,
      oligonucleotides, genes and low molecular weight drugs. In several cases, a >100
      fold increase in biological activity has been observed.

PMID- 14706448
TI  - Plasticity of human chromosome 3 during primate evolution.
AB  - Comparative mapping of more than 100 region-specific clones from human chromosome
      3 in Bornean and Sumatran orangutans, siamang gibbon, and Old and New World
      monkeys allowed us to reconstruct ancestral simian and hominoid chromosomes. A
      single paracentric inversion derives chromosome 1 of the Old World monkey
      Presbytis cristata from the simian ancestor. In the New World monkey Callithrix
      geoffroyi and siamang, the ancestor diverged on multiple chromosomes, through
      utilizing different breakpoints. One shared and two independent inversions derive
      Bornean orangutan 2 and human 3, implying that neither Bornean orangutans nor
      humans have conserved the ancestral chromosome form. The inversions, fissions,
      and translocations in the five species analyzed involve at least 14 different
      evolutionary breakpoints along the entire length of human 3; however, particular
      regions appear to be more susceptible to chromosome reshuffling. The ancestral
      pericentromeric region has promoted both large-scale and micro-rearrangements.
      Small segments homologous to human 3q11.2 and 3q21.2 were repositioned
      intrachromosomally independent of the surrounding markers in the orangutan
      lineage. Breakage and rearrangement of the human 3p12.3 region were associated
      with extensive intragenomic duplications at multiple orangutan and gibbon
      subtelomeric sites. We propose that new chromosomes and genomes arise through
      large-scale rearrangements of evolutionarily conserved genomic building blocks
      and additional duplication, amplification, and/or repositioning of inherently
      unstable smaller DNA segments contained within them.

PMID- 14706449
TI  - A 1.4-Mb interval RH map of horse chromosome 17 provides detailed comparison with
      human and mouse homologues.
AB  - Comparative genomics has served as a backbone for the rapid development of gene
      maps in domesticated animals. The integration of this approach with radiation
      hybrid (RH) analysis provides one of the most direct ways to obtain physically
      ordered comparative maps across evolutionarily diverged species. We herein report
      the development of a detailed RH and comparative map for horse chromosome 17
      (ECA17). With markers distributed at an average interval of every 1.4 Mb, the map
      is currently the most informative among the equine chromosomes. It comprises 75
      markers (56 genes and 19 microsatellites), of which 50 gene specific and 5
      microsatellite markers were generated in this study and typed to our 5000-rad
      horse x hamster whole genome RH panel. The markers are dispersed over six RH
      linkage groups and span 825 cR(5000). The map is among the most comprehensive
      whole chromosome comparative maps currently available for domesticated animals.
      It finely aligns ECA17 to human and mouse homologues (HSA13 and MMU1, 3, 5, 8,
      and 14, respectively) and homologues in other domesticated animals. Comparisons
      provide insight into their relative organization and help to identify
      evolutionarily conserved segments. The new ECA17 map will serve as a template for
      the development of clusters of BAC contigs in regions containing genes of
      interest. Sequencing of these regions will help to initiate studies aimed at
      understanding the molecular mechanisms for various diseases and inherited
      disorders in horse as well as human.

PMID- 14706450
TI  - Linkage of the locus for canine dewclaw to chromosome 16.
AB  - The canine species, including wolf and jackal, have four digits on the hind limb.
      It was thought that an extra first digit on the hind limb, named dewclaw, was a
      hereditary defect. For genetically related canine pedigrees with 73 members with
      dewclaws, we carried out a genome-wide scan for linkage with microsatellites.
      With an assumption of autosomal dominant mode of inheritance, significant
      linkages were detected for the markers on canine chromosome 16. The maximum two
      point lod score of 20.76 was obtained for the REN85M08/REN85N14 markers at a
      recombination fraction of 0.00. For efficient analysis of linkage, a revised
      order of the chromosomal markers was established by assigning all the existing
      markers from the previous linkage and radiation hybrid maps. A chromosome-wide
      haplotype analysis revealed the location of the dewclaw locus within a few
      centimorgan intervals delimited by the UCMCF12 and CXX876 markers. Canine
      chromosome 16 is known to have syntenic relationships with human chromosomes 4q,
      7q, and 8p.

PMID- 14706451
TI  - A physical map of the genomic region on mouse chromosome 3 containing the
      hindshaker (hsh) mutation.
AB  - Hindshaker (hsh), a spontaneous, autosomal recessive mouse mutation, displays a
      developmentally dependent tremor of the hindquarters due to hypomyelination in
      the CNS. This myelin deficit is followed by progressive, but incomplete, recovery
      by postnatal day 42. Herein we describe the construction of a genomic contig
      spanning the interval between the markers D3Mit187 (42.4 cM) and D3Mit232 (45.2
      cM) on mouse chromosome 3, which we have previously shown to contain the hsh
      mutation. A physical map, covering approximately 3.5 Mb, was constructed from a
      series of overlapping yeast and bacterial artificial chromosomes. A 1.2- to 1.4
      Mb segment central to the contig was compared extensively with the syntenic
      regions in human (chromosome 1q21-q23) and rat (chromosome 2). We present new
      data on 10 genes erroneously assigned to this area and on another 6 genes
      previously assigned elsewhere. For absent genes, our work suggests that they are
      telomeric to the region encompassed in our map. Accordingly, our findings both
      map the area surrounding the hsh mutation and present important corrections to
      the current maps in an area rich in genes related to the nervous system.

PMID- 14706452
TI  - Cloning of the rat beta-catenin gene (Ctnnb1) promoter and its functional
      analysis compared with the Catnb and CTNNB1 promoters.
AB  - Considerable recent interest has focused on the stabilization and accumulation of
      beta-catenin protein in human and animal tumors and the corresponding activation
      of downstream beta-catenin/TCF/LEF target genes. However, there is only sparse
      information on the regulation of beta-catenin expression at the transcriptional
      level and its possible involvement in physiological and pathophysiological
      processes. We report here the cloning and characterization of a 3.6-kb promoter
      fragment from the rat beta-catenin gene, Ctnnb1, and its comparison with
      corresponding promoters from the mouse and human genes, Catnb and CTNNB1. Several
      AP1 binding sites were confirmed in the promoters of all three species using
      mobility shift and reporter assays, and one putative TCF/LEF site also was
      observed in the promoter of CTNNB1. Subsequently, protein/DNA array analyses
      identified numerous other transcription factors through their high-affinity
      binding to the Ctnnb1 promoter, including E2F1, NFkappaB, MEF1, Pax5, ISRE2,
      Smad3/4, GATA, and ZIC. The strong binding of E2F1 and NFkappaB is especially
      noteworthy, because the former transcription factor is regulated by cyclin D1, a
      downstream target of beta-catenin/TCF/LEF signaling, whereas the latter
      transcription factor has been implicated in "cross talk" between the Wnt and the
      NFkappaB signaling pathways. These results are discussed in terms of their
      implications for human cancer development and specifically the various tumors in
      which beta-catenin mRNA is overexpressed, as well as for embryonic development,
      when reversible changes in beta-catenin expression occur in response to secreted
      Wnt ligands. The findings reported here should provide important avenues for
      further research focused on the regulation of Ctnnb1 activity, including the
      ability of beta-catenin/Tcf downstream targets to modulate beta-catenin
      expression at the transcriptional level.

PMID- 14706454
TI  - LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily
      conserved mitochondrial protein.
AB  - The leucine zipper-, EF-hand-containing transmembrane protein 1 (LETM1) has
      recently been cloned in an attempt to identify genes deleted in Wolf-Hirschhorn
      syndrome (WHS), a microdeletion syndrome characterized by severe growth and
      mental retardation, hypotonia, seizures, and typical facial dysmorphic features.
      LETM1 is deleted in almost all patients with the full phenotype and has recently
      been suggested as an excellent candidate gene for the seizures in WHS patients.
      We have shown that LETM1 is evolutionarily conserved throughout the eukaryotic
      kingdom and exhibits homology to MDM38, a putative yeast protein involved in
      mitochondrial morphology. Using LETM1-EGFP fusion constructs and an anti-rat
      LetM1 polyclonal antibody we have demonstrated that LETM1 is located in the
      mitochondria. The present study presents information about a possible function
      for LETM1 and suggests that at least some (neuromuscular) features of WHS may be
      caused by mitochondrial dysfunction.

PMID- 14706453
TI  - Molecular cloning, chromosomal mapping, and characteristic expression in tooth
      organ of rat and mouse Krox-25.
AB  - A novel member of the Krox family of proteins, designated Krox-25, was identified
      by screening clones from the cDNA libraries of a rat incisor and mouse embryo
      craniofacial tissue. Rat and mouse Krox-25 mRNAs are about 2.4 kb long, encoding
      225 and 224 amino acids, respectively. Krox-25 consists of five zinc finger
      motifs homologous to the Drosophila Kruppel segmentation gene and also contains
      several consensus amino acid sequences for a protein kinase C binding domain.
      Northern blot analysis revealed an intense expression of Krox-25 mRNA in rat and
      mouse teeth, although it was expressed weakly in other tissues, including
      calvaria, brain, lung, thymus, kidney, and submandibular gland of mouse. In situ
      hybridization showed that Krox-25 mRNA began to be expressed weakly in the early
      odontogenic mesenchyme and primitive enamel epithelium located at the apical end
      of the rat incisor, and Krox-25 expression increased in the presecretory
      ameloblasts and became intense in the secretory ameloblasts. This expression was
      also similar to the results of immunohistochemistry and Western blot, especially
      the Krox-25 localization in the nuclei of enamel epithelial cells. These results
      suggest that Krox-25 plays an important role as a transcription factor for the
      cytodifferentiation and amelogenesis of enamel epithelium.

PMID- 14706455
TI  - Characterization of the segmental duplication LCR7-20 in the human genome.
AB  - Our previous study described the amplification of a genomic sequence containing
      exon 9 of CFTR in the human genome. Here we report that this CFTR sequence is
      part of a large duplicated sequence unit, provisionally named LCR7-20. Through
      successive screening of two human chromosome 7-specific cosmid libraries to
      construct a cosmid contig, we assembled two sequenced BAC clones into a single
      contig containing a prototypic LCR7-20 unit. Subsequent searches of existing
      human genome sequences identified additional six copies of LCR7-20-like sequences
      with more than 90% sequence homology. Additional genomic clones containing LCR7
      20-like sequences were then isolated from total genomic BAC and PAC libraries.
      Restriction fragment analysis and limited sequencing data indicated that there
      could be around 30 copies of LCR7-20-like sequences in the human genome and that
      the average region of homology could extend over 120 kb. As indicated by
      fluorescence in situ hybridization analysis, LCR7-20-like sequences are dispersed
      on different chromosomes, mainly in the centromeric and pericentromeric regions,
      and some may exist in tandem copies. Our study also indicates that many genomic
      regions containing LCR7-20's either have been misassembled or are missing in
      current versions of the human genome sequence.

PMID- 14706457
TI  - Gene expression profiles in end-stage human idiopathic dilated cardiomyopathy:
      altered expression of apoptotic and cytoskeletal genes.
AB  - Dilated cardiomyopathy is now the leading cause of cardiovascular morbidity and
      mortality. While the molecular basis of this disease remains uncertain, evidence
      is emerging that gene expression profiles of left ventricular myocardium isolated
      from failing versus nonfailing patients differ dramatically. In this study, we
      use high-density oligonucleotide microarrays with approximately 22000 probes to
      characterize differences in the expression profiles further. To facilitate
      interpretation of experimental data, we evaluate algorithms for normalization of
      hybridization data and for computation of gene expression indices using a control
      spike-in data set. We then use these methods to identify statistically
      significant changes in the expression levels of genes not previously implicated
      in the molecular phenotype of heart failure. These regulated genes take part in
      diverse cellular processes, including transcription, apoptosis, sarcomeric and
      cytoskeletal function, remodeling of the extracellular matrix, membrane
      transport, and metabolism.

PMID- 14706456
TI  - Characterization of the murine orphan G-protein-coupled receptor gene Rai3 and
      its regulation by retinoic acid.
AB  - A retinoic acid-inducible gene (RAI3) encoding an orphan G-protein-coupled
      receptor is regulated during embryonal carcinoma differentiation. To elucidate
      the mechanisms that mediate its regulation, we isolated and characterized the
      mouse gene (Rai3) and promoter region. Rai3 spans about 18 kb containing four
      exons separated by three introns and maps to mouse chromosome 6 near D6mit25. A
      functional analysis of the Rai3 gene promoter revealed that the proximal region
      harbors most of the elements necessary for its regulation, including GC boxes and
      Sp1-, AP1-, and AP2-binding sites. A functional retinoic acid response element
      direct repeat of two novel motifs separated by a 5-bp spacer (5'
      TGTCCCtcggtTCACCC-3') was identified at -64 bp upstream of the transcription
      start site using the methods of promoter truncation, electrophoretic mobility
      shift assay, and mutation analysis. These findings provide strong evidence that
      Rai3 is regulated directly by retinoic acid via its receptors.

PMID- 14706458
TI  - Generation of a complete set of human telomeric band painting probes by
      chromosome microdissection.
AB  - Chromosomal rearrangements involving telomeric bands have been frequently
      detected in many malignancies and congenital diseases. To develop a useful tool
      to study chromosomal rearrangements within the telomeric band effectively and
      accurately, a whole set of telomeric band painting probes (TBP) has been
      generated by chromosome microdissection. The intensity and specificity of these
      TBPs have been tested by fluorescence in situ hybridization and all TBPs showed
      strong and specific signals to target regions. TBPs of 6q and 17p were
      successfully used to detect the loss of the terminal band of 6q in a
      hepatocellular carcinoma cell line and a complex translocation involving the 17p
      terminal band in a melanoma cell line. Meanwhile, the TBP of 21q was used to
      detect a de novo translocation, t(12;21), and the breakpoint at 21q was located
      at 21q22.2. Further application of these TBPs should greatly facilitate the
      cytogenetic analysis of complex chromosome rearrangements involving telomeric
      bands.

PMID- 14706459
TI  - Two new mouse chromosome 11 balancers.
AB  - Segmental inversions causing recombination suppression are an essential feature
      of balancer chromosomes. Meiotic crossing over between homologous chromosomes
      within an inversion interval will lead to nonviable gametes, while gametes
      generated from recombination events elsewhere on the chromosome will be
      unaffected. This apparent recombination suppression has been widely exploited in
      genetic studies in Drosophila to maintain and analyze stocks carrying recessive
      lethal mutations. Balancers are particularly useful in mutagenesis screens since
      they help to establish the approximate genomic location of alleles of genes
      causing phenotypes. Using the Cre-loxP recombination system, we have constructed
      two mouse balancer chromosomes carrying 8- and 30-cM inversions between Wnt3 and
      D11Mit69 and between Trp53 and EgfR loci, respectively. The Wnt3-D11Mit69
      inversion mutates the Wnt3 locus and is therefore homozygous lethal. The Trp53
      EgfR inversion is homozygous viable, since the EgfR locus is intact and mutations
      in p53 are homozygous viable. A dominantly acting K14-agouti minigene tags both
      rearrangements, which enables these balancer chromosomes to be visibly tracked in
      mouse stocks. With the addition of these balancers to the previously reported
      Trp53-Wnt3 balancer, most of mouse chromosome 11 is now available in balancer
      stocks.

PMID- 14706460
TI  - Genotyping with TaqMAMA.
AB  - TaqMAMA combines the quantitative strengths of TaqMan with the allele-specific
      PCR of MAMA. In this article we develop TaqMAMA as a technique for screening
      human DNA samples for known genetic polymorphisms. In the first set of
      experiments, plasmids that model all types of genetic polymorphisms were used to
      understand the relationship between TaqMAMA primer/template mismatches and their
      strength of allelic discrimination. These data can be used to improve allelic
      discrimination of other primer extension genotyping methodologies through
      directed use of nucleotide mismatches. We used the data to derive a guide for
      TaqMAMA primer design and DNA strand selection for TaqMAMA genotyping assays. The
      guide was then used to develop assays for 11 known and novel human genetic
      polymorphisms. Genotypes were assigned quickly and accurately in all cases.
      TaqMAMA genotyping assays require minimal development time, have a high
      probability of success, produce reliable data that are straightforward to
      analyze, and are very cost-competitive.

PMID- 14706461
TI  - Single-stranded linear amplification protocol results in reproducible and
      reliable microarray data from nanogram amounts of starting RNA.
AB  - The range of scientific questions utilizing DNA microarray techniques is limited
      by the fact that these methods require 5-40 microg of high-quality total RNA.
      Thus, methods that reliably amplify the starting RNA amount could expand the
      applicability of DNA microarray technology. We developed a single-stranded linear
      amplification protocol (SLAP) that combines the reproducibility of in vitro
      transcription and the amplification robustness of polymerase chain reactions. We
      compared SLAP to the NIH-IVT amplification protocol. SLAP displayed excellent
      conservation of the 5'/3' signal and demonstrated the most robust amplification,
      producing the recommended amounts of biotin-labeled RNA with as little as 0.002
      microg of starting RNA. Both SLAP and NIH-IVT methods demonstrated good
      reproducibility, but SLAP maintained the highest level of reliability with RNA
      starting amounts of <0.05 microg. These results suggest that SLAP is an excellent
      alternative to IVT-based amplification protocols when RNA is limited by small
      sample size.

PMID- 14706462
TI  - Target-selected mutagenesis of the rat.
AB  - The rat is one of the most extensively studied model organisms, and with its
      genome being sequenced, tools to manipulate gene function in vivo have become
      increasingly important. We here report proof of principle for target-selected
      mutagenesis as a reverse genetic or knockout approach for the rat.

PMID- 14706463
TI  - Direct IBD mapping: identical-by-descent mapping without genotyping.
AB  - Direct identical-by-descent (IBD) mapping is a technique, that combines genomic
      mismatch scanning (GMS) and DNA microarray technology, for mapping regions shared
      IBD between two individuals without locus-by-locus genotyping or sequencing. The
      lack of reagents has limited its widespread application. In particular, two key
      reagents have been limiting, 1). mismatch repair proteins MutS, L and H, and 2).
      genomic microarrays for identifying the genomic locations of the GMS-selected IBD
      fragments. Here, we describe steps that optimized the procedure and resources
      that will facilitate the development of direct IBD mapping.

PMID- 14706464
TI  - The neurophysiology of brain injury.
AB  - OBJECTIVE: This article reviews the mechanisms and pathophysiology of traumatic
      brain injury (TBI). METHODS: Research on the pathophysiology of diffuse and focal
      TBI is reviewed with an emphasis on damage that occurs at the cellular level. The
      mechanisms of injury are discussed in detail including the factors and time
      course associated with mild to severe diffuse injury as well as the
      pathophysiology of focal injuries. Examples of electrophysiologic procedures
      consistent with recent theory and research evidence are presented. RESULTS:
      Acceleration/deceleration (A/D) forces rarely cause shearing of nervous tissue,
      but instead, initiate a pathophysiologic process with a well defined temporal
      progression. The injury foci are considered to be diffuse trauma to white matter
      with damage occurring at the superficial layers of the brain, and extending
      inward as A/D forces increase. Focal injuries result in primary injuries to
      neurons and the surrounding cerebrovasculature, with secondary damage occurring
      due to ischemia and a cytotoxic cascade. A subset of electrophysiologic
      procedures consistent with current TBI research is briefly reviewed. CONCLUSIONS:
      The pathophysiology of TBI occurs over time, in a pattern consistent with the
      physics of injury. The development of electrophysiologic procedures designed to
      detect specific patterns of change related to TBI may be of most use to the
      neurophysiologist. SIGNIFICANCE: This article provides an up-to-date review of
      the mechanisms and pathophysiology of TBI and attempts to address misconceptions
      in the existing literature.

PMID- 14706465
TI  - Estimating cardiac autonomic activity during sleep: impedance cardiography,
      spectral analysis, and Poincare plots.
AB  - OBJECTIVE: To compare noninvasive measures of cardiac autonomic activity during
      sleep. METHODS: The absolute and normalized (n.u.) high and low frequency peaks
      from the spectral analysis of R-R intervals (HF, LF, HFn.u., LFn.u.), LF/HF
      ratio, pre-ejection period (PEP) from impedance cardiography, and the
      autocorrelation coefficient (rRR) as illustrated in Poincare plots were measured
      during night-time sleep in 9 young healthy subjects. Heart rate and blood
      pressure were also recorded. RESULTS: Heart rate was significantly associated
      with cardiac sympathetic activity (PEP, average r=-0.46), but not with cardiac
      parasympathetic activity (HF, average r=-0.17). rRR was significantly associated
      with heart rate (average r=0.41), and LF/HF (average r=0.69), but not with PEP or
      HF. From NREM to REM sleep, heart rate, LFn.u., LF and rRR significantly
      increased, HFn.u. significantly decreased, LF/HF showed an increasing trend
      (P=0.07) and PEP showed a decreasing trend (P=0.06). Blood pressure and HF were
      highly variable without significant changes from NREM to REM sleep. CONCLUSIONS:
      Cardiac parasympathetic activity (HF) does not vary greatly between sleep stages.
      Cardiac sympathetic activity (PEP) decreases linearly during sleep. rRR and LF/HF
      can track sympathovagal changes during sleep, but cannot differentiate between
      changes in cardiac parasympathetic and sympathetic activity. The relative
      advantages and disadvantages of the different measures are discussed.

PMID- 14706466
TI  - Absence of gaze direction effects on EEG measures of sensorimotor function.
AB  - OBJECTIVE: Gaze direction is known to modulate the activation patterns of
      sensorimotor areas as seen at the single cell level and in functional magnetic
      resonance imaging (fMRI). To determine whether such gaze direction effects can be
      observed in scalp-recorded electroencephalogram (EEG) measures of sensorimotor
      function we investigated somatosensory evoked potentials (SEPs) and steady state
      movement related cortical potentials (MRPs). METHODS: In two separate
      experiments, SEPs were elicited by electrical stimulation of the median nerve
      (experiment 1) and steady state MRPs were induced by 2 Hz tapping paced by an
      auditory cue (experiment 2), while subjects directed their gaze 15 degrees to the
      left or to the right. RESULTS: Gaze direction failed to produce any appreciable
      differences in the waveforms of the SEPs or MRPs. In particular, there was no
      effect on peak amplitude, peak latency and peak scalp topography measures of SEP
      and MRP components, or on spatial or temporal parameters of dipole models of the
      underlying cortical generators. Additional frequency domain analyses did not
      reveal reliable gaze-related changes in induced power at electrode sites
      overlying somatosensory and motor areas, or in coherence between pairs of
      parietal, central and frontal electrodes, across a broad range of frequencies.
      CONCLUSIONS: EEG measures of sensorimotor function, obtained in a non-visual
      motor task, are insensitive to modulatory effects of gaze direction in
      sensorimotor areas that are observable with fMRI.

PMID- 14706467
TI  - Quantitative EEG and perfusional single photon emission computed tomography
      correlation during long-term donepezil therapy in Alzheimer's disease.
AB  - OBJECTIVE: There is an increasing interest in the effects of the
      acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD), as
      investigated by means of objective, neurophysiological tools. In an open-label
      study, we evaluated the neurophysiological effects of chronic administration of
      donepezil to AD patients, by means of a correlative approach between quantitative
      EEG (qEEG) and perfusional brain single photon emission computed tomography
      (SPECT). METHODS: Sixteen patients (mean age: 74.8+/-7.9 years) with mild to
      moderate AD (MMSE score >13, mean: 20.7+/-4.6) underwent qEEG and SPECT
      examinations at the time of diagnosis (t0) and after approximately 1 year of
      donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime)
      was performed by means of a high-resolution SPECT camera; the qEEG was recorded
      from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean
      frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4
      brain regions (one frontal and one temporal-parietal in each hemisphere) was
      chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between
      t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and
      t1, as well as the relationships between SPECT and qEEG changes, were assessed by
      statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster
      level). RESULTS: Between t0 and t1, the MMSE score significantly (P<0.05)
      decreased (from 20.7+/-4.64 to 19.1+/-5.09; 95% confidence interval: 1.14) and
      qEEG was unchanged. There was no regional perfusion decrease; a small area of
      relative perfusion increase was observed, including the right occipital cuneus
      and the left lingual gyrus. A positive correlation was found between the right
      frontal MF and brain perfusion in the left superior parietal lobule. A post hoc
      SPM analysis (height threshold: P=0.01) showed a positive correlation between
      brain perfusion and each of the 4 qEEG MF values in the left parietal lobe,
      including the precuneus, the superior parietal lobule, and the post-central
      gyrus. CONCLUSIONS: The posterior parietal region, which is involved in memory
      and attention, is often affected by hypoperfusion in AD, as a likely consequence
      of disconnection from the atrophic mesial temporal cortex. Metabolic activation
      induced by AChEIs may especially influence this disconnected but still not
      grossly impaired area, which could be one of the pathophysiological substrates of
      the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG,
      reflecting the rather diffuse changes in AD, is further confirmed.

PMID- 14706468
TI  - Electrophysiological characterization of spontaneous and carbamazepine-induced
      epileptic negative myoclonus in benign childhood epilepsy with centro-temporal
      spikes.
AB  - OBJECTIVE: Epileptic negative myoclonus (ENM), a transient muscular atonic
      phenomenon time-locked to epileptiform EEG abnormalities, is often observed in
      children with benign childhood epilepsy with centro-temporal spikes (BECTS). In
      some, for unknown reasons, ENM can be worsened by carbamazepine (CBZ). We
      describe two children aged 11 and 15 years, in whom CBZ precipitated seizure
      worsening and ENM. We investigated the morphological and topographic features of
      the EEG abnormalities while on CBZ and after CBZ withdrawal and compared them
      with those from 9 children with classical BECTS. The aim of the study was to
      identify possible electrophysiological specificities in patients who eventually
      develop ENM during CBZ treatment. METHODS: The characterization of EEG
      abnormalities, related (R) and unrelated to ENM (U), in patients with ENM and
      rolandic discharges (RD) and in matched controls with BECTS was performed based
      on polygraphic digital EEG recordings. Off-line time-domain analysis included
      correlation coefficient between EEG and EMG channels, quantitative analysis on
      ENM, and topographic analysis on spike-and-wave complexes. Z-score test and
      paired t test were used when appropriate for statistical analysis on R, U and RD.
      RESULTS: Recordings in both children with BECTS and ENM while on CBZ showed
      frequent R discharges (mean interval between R=19.89+/-9.4 s in patient 1; 2.16+/
      1.2 s in patient 2). Withdrawal of CBZ produced abatement of R (no R recorded in
      patient 1; 5.69+/-7.1 s in patient 2) and reduction of the slow wave component of
      R (P<0.01). Morphology and topography of R and RD differed in field distribution,
      amplitude (P<0.01) and duration (P<0.01) of the slow wave component. RD and U did
      not show a significantly different morphology and field distribution.
      CONCLUSIONS: Our findings suggest that an increased cortical inhibition could be
      the electrophysiological correlate of CBZ-induced ENM. If confirmed on a larger
      series, the presence of spike-wave (rather than sharp waves) discharges in
      children with BECTS might be used as an electrophysiological predictor of an
      abnormal response to CBZ.

PMID- 14706469
TI  - Median nerve damage during two-portal endoscopic carpal tunnel release.
AB  - OBJECTIVE: To evaluate the adverse effects of Chow's two-portal endoscopic carpal
      tunnel release (ECTR) performed by an experienced surgeon on median nerve
      function in patients with idiopathic carpal tunnel syndrome, as compared to open
      carpal tunnel release (OCTR). METHODS: Eighty-seven hands subjected to ECTR and
      65 hands subjected to OCTR were reviewed. Both groups of patients were similar
      with regard to age, gender, and severity of the disease. Both groups were
      compared for the number of hands showing worsening of motor distal latency,
      sensory conduction velocity, and sensory disturbance after surgery. RESULTS:
      Thirteen hands of 12 patients showed worsening of median nerve function after
      ECTR, while only one hand showed worsening after OCTR. This difference was
      statistically significant (p=0.0041). CONCLUSIONS: Median nerve damage, although
      transient or not serious, may occur even if the procedure is done correctly.

PMID- 14706470
TI  - Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln
      mutation.
AB  - OBJECTIVE: In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological
      and histopathological studies have suggested either a demyelinating or an axonal
      polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve
      conductions between and within nerves. METHODS: Two men and one woman have been
      studied by conduction velocities, sural nerve biopsy with morphometry (one man)
      and DNA analysis. RESULTS: In both men motor conduction velocities were slowed in
      the demyelinating range, conduction velocity differences among nerves in the same
      subject varied from 13 to 24 m/s, and distal median compound muscle action
      potential (CMAP) amplitudes were 3-5 times reduced compared to ulnar CMAPs.
      Abnormal area reduction or excessive temporal dispersion of proximal CMAP was
      present in at least two nerves in all patients. Sural nerve biopsy showed
      reduction of large myelinated fibres, cluster formations, occasional onion bulbs.
      Teased fibres study revealed short internodes for fibre diameter, enlarged
      Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA
      analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients.
      CONCLUSIONS: In this family conduction slowing and segmental conduction
      abnormalities, in absence of morphological evidence of de-remyelination, may be
      related to short internodes, widened Ranvier nodes and the specific effect of the
      mutation. The occurrence in some CMTX patients of a non uniform involvement
      between and within nerves, as in acquired demyelinating neuropathies, should be
      kept in mind to avoid misdiagnoses.

PMID- 14706471
TI  - Minimal tonic firing rates of human lateral pterygoid single motor units.
AB  - OBJECTIVE: The minimal tonic firing rates (the lowest firing rates at which motor
      units fire regularly; MTFR) of single motor units (SMUs) within the lateral
      pterygoid muscle have not been widely investigated. The aims of this study were
      (a) to identify MTFR of SMUs within the inferior head (IHLP) and superior head
      (SHLP) of the lateral pterygoid muscle during horizontal jaw movements, and (b)
      to determine whether these MTFR vary with movement direction. METHODS: Twenty
      subjects moved the jaw to maintain SMU firing at the lowest continuous firing
      rate. SMU activity was recorded from computer-tomography-verified sites within
      the IHLP or SHLP. RESULTS: In the IHLP, the mean (+/-SD) MTFR for contralateral
      movement (15.6+/-2.3 imp/s; n=22 SMUs) were not significantly different from
      those during protrusion (16.3+/-3.4 imp/s; n=19). In the SHLP, the mean (+/-SD)
      MTFR for contralateral, ipsilateral movement, and protrusion were 14.7+/-2.5
      imp/s (n=10), 13.2+/-2.1 imp/s (n=8), and 16.2+/-3.7 imp/s (n=2), respectively.
      CONCLUSIONS: Lateral pterygoid SMUs have greater MTFR than previously reported in
      the masseter and IHLP, namely 5-8 and 8-10 imp/s, respectively. The MTFR did not
      vary with the task within each muscle head. SIGNIFICANCE: Some physiological
      properties of lateral pterygoid SMUs may be different from those in other jaw
      muscles.

PMID- 14706472
TI  - Effects of experimental muscle pain on mechanical properties of single motor
      units in human masseter.
AB  - OBJECTIVE: Muscle pain is known to influence muscle activity but the details of
      its effects on the mechanical properties of single motor units (SMU) have not
      been described. We have recently reported a decreased firing rate of SMU in the
      human masseter muscle during painful contractions with a constant force output.
      Force output can be modulated by the SMU discharge rate in relation to the
      contractile properties of SMU. Therefore, the objective of the present study was
      to measure the mechanical properties of SMU in the masseter to clarify the
      mechanism which underlies the decrease in SMU firing rate during jaw-muscle pain.
      METHODS: A spike-triggered averaging (STA) technique was used to determine the
      mechanical properties of low-threshold SMU in the masseter muscle recorded with
      fine wire electrodes during a voluntary isometric contraction. The twitch
      amplitude, contraction time, and half-relaxation time were determined from the
      averaged force records before and during experimental jaw-muscle pain induced by
      injection of 0.2 ml (100 microg/ml) capsaicin in 8 healthy subjects. Injections
      of 0.2 ml isotonic saline served as a non-painful control in 11 healthy subjects.
      RESULTS: The twitch amplitude was significantly increased during capsaicin-evoked
      muscle pain (P<0.001) without significant changes of half-relaxation time and
      contraction time. No significant changes in SMU twitch properties were observed
      during the control injections. CONCLUSIONS: Potentiation of twitch force could be
      a possible compensatory mechanism to maintain a constant force output during
      painful isometric contractions when SMU firing decreases. This finding therefore
      provides new information on the adaptation of motor function by muscle pain.

PMID- 14706473
TI  - Motor excitability in myopathy.
AB  - OBJECTIVE: To explore whether patients with myopathy present changes in
      motoneuronal excitability. METHODS: Patients with well-defined myopathies were
      studied with single and paired pulse transcranial magnetic stimulations and
      electrical nerve stimulations to explore neuronal motor excitability. Motor
      evoked potentials were recorded from the clinically unaffected first dorsal
      interosseous muscle (n=10) and the paretic deltoid muscle (n=8). RESULTS:
      Compared to an age-matched healthy control group, myopathic patients showed a
      reduction of intracortical inhibition, enhancements of alpha-motoneuron
      excitability and increased amplitudes of motor-evoked potentials during target
      muscle contraction. These alterations were present in clinically affected and
      clinically unaffected muscles. CONCLUSION: In myopathy, nervous system
      excitability may be altered, presenting as a motor disinhibition on cortical and
      subcortical levels.

PMID- 14706474
TI  - Visual information processing in dyslexic children.
AB  - OBJECTIVE: Several studies presented evidence for magnocellular deficits in
      dyslexics both in behavioural as well as in electrophysiological data of local
      electrode sites. We investigated two well-known paradigms (motion-onset and
      random-dot-kinematogram) with regard to global electrophysiological parameters.
      METHODS: Twenty-one-channel event-related potentials (ERPs) of 16 dyslectic and
      15 control children were analyzed with reference-independent methods. For each
      paradigm quasi stable microstates were identified by means of a data-driven
      segmentation procedure and compared between both groups. RESULTS: Differences in
      global ERP responses between dyslexic and control children could be found for
      rapid moving gratings but not for the dot coherence. CONCLUSIONS: Dyslexic
      children seem to have some highly specific visual deficits in processing moving
      stimuli. These deficits can be related to the magnocellular system.

PMID- 14706475
TI  - The physiological functional loss of single thenar motor units in the stroke
      patients: when does it occur? Does it progress?
AB  - OBJECTIVE: We examined the time at which loss of functioning motor units occurs
      on the hemiparetic side, the relationship between that loss and hemiparetic
      severity, and how long that loss continues. METHODS: Sample surface motor unit
      action potentials (S-MUAPs) were evoked in F-waves. They entirely represent the
      activity of the relative numbers of different shape S-MUAPs for each abductor
      pollicis brevis muscle. S-MUAPs from selected population of F-waves were averaged
      after aligning onset latency. Motor unit number was obtained by dividing the
      maximum M-potential negative peak amplitude by the averaged S-MUAP one. RESULTS:
      The motor unit number on the hemiparetic side was significantly lower than that
      on the unaffected side in stroke patients who had suffered hemiparesis for more
      than 9 days. This motor unit loss was greater in patients with severe
      hemiparesis. One year after onset, the chronic stroke patients showed the same
      motor unit loss on hemiparetic side as they had 3-4 months after onset.
      CONCLUSIONS: Motor unit loss on the hemiparetic side is present as early as the
      second week after onset and is correlated with hemiparesis severity, and this
      loss continues out to 1 year. This may be due to trans-synaptic degeneration that
      occurs secondarily to upper motor neuron lesion.

PMID- 14706476
TI  - Reduction in amplitude of the subcortical low- and high-frequency somatosensory
      evoked potentials during voluntary movement: an intracerebral recording study.
AB  - OBJECTIVE: To investigate whether the reduction of amplitude of the scalp
      somatosensory evoked potentials (SEPs) during movement (gating) is due to an
      attenuation of the afferent volley at subcortical level. METHODS: Median nerve
      SEPs were recorded from 9 patients suffering from Parkinson's disease, who
      underwent implant of intracerebral (IC) electrodes in the subthalamic nucleus or
      in the globus pallidum. SEPs were recorded from Erb's point ipsilateral to
      stimulation, from the scalp surface and from the IC leads, at rest and during a
      voluntary flexo-extension movement of the stimulated wrist. The recorded IC
      traces were submitted to an off-line filtering by a 300-1500 bandpass to obtain
      the high-frequency SEP bursts. RESULTS: IC leads recorded a triphasic component
      (P1-N1-P2) from 14 to 22 ms of latency. The amplitudes of the scalp N20, P20 and
      N30 potentials and of the IC triphasic component were significantly decreased
      during movement, while the peripheral N9 amplitude remained unchanged. Also the
      IC bursts, whose frequency was around 1000 Hz, were reduced in amplitude by the
      voluntary movement. CONCLUSIONS: Since the IC triphasic component is probably
      generated by neurons of the thalamic ventro-postero-lateral nucleus, which
      receive the somatosensory afferent volley, the P1-N1 amplitude reduction during
      movement suggests that the gating phenomenon involves also the subcortical
      structures.

PMID- 14706477
TI  - Direct recording of the output of the motor cortex produced by transcranial
      magnetic stimulation in a patient with cerebral cortex atrophy.
AB  - OBJECTIVE: To examine the descending motor activity evoked by transcranial
      magnetic stimulation (TMS) in a chronic alcoholic patient with a slight atrophy
      of the peri-central cortex and compare with that observed in neurologically
      intact subjects. METHODS: EMGs from the first dorsal interosseous (FDI) muscle,
      and descending activity from an electrode implanted in the high cervical epidural
      space for relief of pain were recorded after TMS of the hand area of motor
      cortex. A figure-of-8 coil was used to induce either a posterior-anterior (PA) or
      a latero-medial (LM) flow across the central sulcus. RESULTS: In intact subjects,
      LM stimulation evoked the earliest volley, which we termed a D wave. This was
      followed by later, presumed I waves at intervals of about 1.5 ms. At a stimulus
      intensity of 120% resting threshold (RMT), up to 5 I waves were seen. PA
      stimulation rarely evoked D waves at intensities up to 120% RMT, but 3 or 4 I
      waves were visible in all subjects. The patient had an increased resting
      threshold, and the descending volleys were dominated by a D wave. I waves were
      unclear, with two possible small peaks at 5.5 and 7.2 ms. CONCLUSIONS: The lack
      of I waves in the patient was probably due to an impairment of interneuronal
      circuitry in the context of the brain damage related to chronic alcohol abuse,
      and is consistent with a trans-synaptic origin of the I waves in humans. The
      intact D wave is consistent with the assumption that the D wave represents direct
      stimulation of the axons of intact corticospinal neurones in the subcortical
      white matter. The patient's increased RMT reflects the fact that usually multiple
      descending volleys are needed to discharge resting spinal motoneurones.

PMID- 14706478
TI  - Reliability of a new measure of H-reflex excitability.
AB  - OBJECTIVE: This study examined the intraclass reliability of different measures
      extracted from Hoffmann reflex (H-reflex) stimulus-response curve that are used
      to assess neuromuscular excitability. The following measures were compared: (1)
      the peak-to-peak amplitude of the H-reflex at a stimulus intensity associated
      with 5% of the maximum M-wave; (2) the slope of the regression line of the H
      reflex stimulus-response curve; and (3) the peak of the first derivative of the H
      reflex stimulus-response curve, a new measure introduced in this paper. METHODS:
      The H-reflex was elicited in the soleus for 24 subjects (12 males and 12 females)
      on 5 separate days. Vibration was applied to the Achilles tendon prior to
      stimulation to test the sensitivity of the measures on test day 4. The stimulus
      intensity was gradually increased from below the threshold for an H-reflex
      response to above the maximum M-wave (Mmax) response. The means of 5 evoked
      potentials at each intensity level were used to create both the H-reflex and M
      wave stimulus-response curves for each subject across test days. Determination of
      reliability involves the consideration of both the stability and consistency of
      the measures. A repeated measures analysis of variance evaluated the stability of
      the group means across test sessions. The consistency of scores within
      individuals was determined by calculating the intraclass correlation coefficient
      (ICC). Calculation of the 95% confidence interval of estimation was used to
      assess significant differences between ICCs. RESULTS: The H-reflex measures were
      both stable and consistent across the first 3 test days. Achilles tendon
      vibration resulted in a profound reduction (59-70%) on test day 4, and then there
      was a return to baseline levels on test day 5. The ICC for H-reflex at a stimulus
      intensity associated with 5% of the maximum M-wave was 0.85. The ICC for the
      slope of the regression line of the H-reflex stimulus-response curve was 0.79,
      while it was 0.89 for the peak of the first derivative of the H-reflex stimulus
      response curve. However, there was no statistical significance (P>0.05) between
      the 3 EMG measures of the H-reflex arc. Maximum M-wave amplitude had an ICC of
      0.96 attesting to careful methodological controls. CONCLUSIONS: The peak of the
      first derivative of the H-reflex stimulus-response curve was shown to have
      comparable sensitivity and reliability as other more established measures.
      SIGNIFICANCE: The first derivative of the H-reflex stimulus-response curve
      provides the rate of change, rather than amplitude, making it a robust measure of
      reflex arc excitability. The higher ICC for the first derivative offers greater
      statistical power, which is of practical significance.

PMID- 14706479
TI  - Alpha and beta oscillatory activity during a sequence of two movements.
AB  - OBJECTIVE: We studied movement-related electroencephalographic oscillatory
      changes in the alpha and beta range during a sequence of two movements in 7
      healthy volunteers, in order to investigate the relationship between these
      changes and each component in the sequence. METHODS: The sequence consisted of a
      wrist active extension-passive flexion followed by a first and second finger
      pincer. A total of 10.5 s sweeps were recorded using the level of surface
      electromyographic (EMG) activity in wrist extensors as trigger, including a 7.5 s
      pre-stimulus. The sweeps were also realigned manually offline using as trigger
      the end of the first EMG burst, or the beginning of the second movement. An index
      of the changes in non-phase-locked energy in the 7-37 Hz range was obtained by
      averaging single-sweep time-frequency transforms. RESULTS: The duration of each
      of the movements in the sequence and the relationship between them were
      compatible with the use of two different motor programmes in the sequence. In the
      beta band, a decrease in energy (event-related desynchronisation, ERD) began 1.5
      s before the onset of the first movement, and was sustained until the end of the
      second movement. No energy increases were observed until the end of the second
      movement. In the alpha band, the ERD began 0.5 seconds before the first movement
      and was sustained throughout the recording. CONCLUSION: These findings suggest
      that the beta-event-related synchronisation is related to the end of the whole
      motor process, and not to the end of each motor programme.

PMID- 14706480
TI  - EEG biofeedback of low beta band components: frequency-specific effects on
      variables of attention and event-related brain potentials.
AB  - OBJECTIVE: To test a common assumption underlying the clinical use of
      electroencephalographic (EEG) biofeedback training (neurofeedback), that the
      modulation of discreet frequency bands is associated with frequency-specific
      effects. Specifically, the proposal was assessed that enhancement of the low beta
      components sensorimotor rhythm (SMR: 12-15 Hz) and beta1 (15-18 Hz) affect
      different aspects of attentional processing. METHODS: Subjects (n=25) were
      randomly allocated to training with either an SMR or beta1 protocol, or to a non
      neurofeedback control group. Subjects were assessed prior and subsequent to the
      training process on two tests of sustained attention. The neurofeedback
      participants were also assessed on target P300 event-related potential (ERP)
      amplitudes in a traditional auditory oddball paradigm. RESULTS: Protocol-specific
      effects were obtained in that SMR training was associated with increased
      perceptual sensitivity 'd prime' (d'), and reduced omission errors and reaction
      time variability. Beta1 training was associated with faster reaction times and
      increased target P300 amplitudes, whereas no changes were evident in the control
      group. CONCLUSIONS: Neurofeedback training of SMR and beta1 band components led
      to significant and protocol-specific effects in healthy subjects. The data can be
      interpreted as indicating a general attention-enhancing effect of SMR training,
      and an arousal-enhancing effect of beta1 training.

PMID- 14706481
TI  - The mismatch negativity (MMN): towards the optimal paradigm.
AB  - OBJECTIVE: Recent studies have shown that the mismatch negativity (MMN), a change
      specific component of the event-related potential (ERP), for particular auditory
      features is degraded in different clinical populations. This suggests that the
      MMN could, in principle, reflect the whole profile and extent of the central
      auditory deficit. In the present article, we tested a new MMN paradigm allowing
      one to obtain MMNs for several auditory attributes in a short time. METHODS: MMN
      responses to changes in frequency, intensity, duration, location, and to a silent
      gap occasionally inserted in the middle of a tone were compared between the
      traditional 'oddball' paradigm (a single type of auditory change in each
      sequence) and the new paradigm (two versions) in which all the 5 types of changes
      appeared within the same sequence. RESULTS: The MMNs obtained in the new paradigm
      were equal in amplitude to those in the traditional MMN paradigm. CONCLUSIONS: We
      propose a new paradigm that can provide 5 different MMNs in the same time in
      which usually only one MMN is obtained. The new paradigm enables one to
      objectively determine the profile of different auditory discrimination abilities
      within a very short recording time.

PMID- 14706482
TI  - Functional lesions and human action monitoring: combining repetitive transcranial
      magnetic stimulation and event-related brain potentials.
AB  - OBJECTIVE: Electrophysiological recordings of the error-related negativity (ERN)
      and functional imaging data point to an involvement of medial frontal cortex
      (including the anterior cingulate cortex, ACC) and dorsolateral prefrontal cortex
      (DLPFC) in the detection and correction of performance errors. Here, we studied
      this network by applying trains of rapid transcranial magnetic stimulation (rTMS)
      prior to the recording of the ERN. METHODS: Low-frequency (0.9 Hz) rTMS was
      applied to medial frontal or lateral frontal regions (different sessions) for 60
      s immediately before each 3 min ERN recording in 11 healthy young subjects. The
      ERN was obtained by multichannel recordings in a typical Eriksen flanker task
      with instructions calling for immediate error correction in case a performance
      error was detected by the subject. Event-related potentials were quantified and
      statistically evaluated using standard methodology. RESULTS: Compared to a no
      stimulation control condition, medial frontal stimulation led to a small but
      reliable decrease in the number of corrected errors as well as to an attenuation
      of the ERN and an increase of the subsequent error-positivity (Pe). No effect on
      these components was seen after lateral frontal stimulation. No reliable effects
      on the lateralized readiness potential were observed. CONCLUSIONS: Functional
      lesions by rTMS appear to interfere with the functions of the medial frontal
      cortex in error detection and correction.

PMID- 14706483
TI  - Determination of cortical language dominance using functional transcranial
      Doppler sonography in left-handers.
AB  - OBJECTIVE: Verbal analytical functions are primarily related to the left
      hemisphere in right-handers, but there is yet no agreement about cortical
      language dominance in left-handers. Also, there are some contradictory reports
      about sex differences in cortical language lateralization. The aim of this study
      is to investigate cortical language dominance in left-handers and to explore
      gender influence on cortical language representation. METHODS: We performed
      functional transcranial Doppler sonography (previous validated for determination
      of cerebral language lateralization) during a word generation task, measuring
      changes in mean cerebral blood flow velocity (BFVmean) in both middle cerebral
      arteries (MCA) in 150 healthy subjects (75 left-handers and 75 right-handers). In
      left-handers we observed significant increase BFVmean in right MCA in 58 (77.3%)
      subjects. Bilateral increase was observed in 11 (14.7%) subjects and increase in
      left MCA in 6 (8%) subjects. In right-handed group 93.3% subjects showed left
      cortical dominance, while 6.7% showed bilateral language representation. RESULTS:
      Current results showed significant (P<0.0001) right hemispheric language
      dominance in healthy left-handed subjects. CONCLUSIONS: Our results showed
      significant difference in hemispheric dominance for verbal function between
      righthanders and lefthanders. Also there is statistically insignificant female
      gender tendency for bilateral hemispheric language representation in both
      handedness.

PMID- 14706485
TI  - Examining the effects of electromagnetic fields emitted by GSM mobile phones on
      human event-related potentials and performance during an auditory task.
AB  - OBJECTIVE: Due to the widespread use of mobile phones (MP), it is important to
      determine whether they affect human physiology. The aim of this study was to
      explore the sensitivity of auditory event-related potentials to electromagnetic
      emissions. METHODS: Twelve participants attended two sessions, 1 week apart.
      Participants performed an auditory oddball task while they were exposed to an
      active MP during one session and sham exposure during the other. Each condition
      lasted 1 h and order was counterbalanced. N100 and P200 latencies and amplitudes
      were analysed for non-target waveforms, and N200 and P300 latencies and
      amplitudes were analysed for target waveforms. RESULTS: In real relative to sham
      exposure N100 amplitude and latency to non-targets were reduced, with the
      reduction larger over midline and right hemisphere sites. P300 latency to targets
      was delayed in the real exposure condition, however as this difference was
      greatest at left frontal and left central sites the interpretation of this result
      is unclear. Reaction time increased in the real relative to sham condition. No
      difference in accuracy was found. CONCLUSIONS: The results suggest that MP
      exposure may affect neural activity, particularly in proximity to the phone,
      however caution should be applied due to the small sample size.

PMID- 14706484
TI  - Human cortical responses during one-bit short-term memory. A high-resolution EEG
      study on delayed choice reaction time tasks.
AB  - OBJECTIVE: We investigated whether a very simple short-term memory (STM) demand
      induces a visible change of EEG rhythms over the two hemispheres. METHODS: High
      resolution EEG was obtained in young adults during two delayed choice reaction
      time tasks. In the STM condition, a simple cue stimulus (one bit) was memorized
      along a brief delay period (3.5-5.5 s). The task was visuo-spatial in nature.
      RESULTS: In the control (NSTM) condition, the cue stimulus remained available
      along the delay period. Compared to the control condition, the theta power (4-6
      Hz) decreased in left frontal and bilateral parietal areas (delay period).
      Furthermore, low alpha power (6-8 Hz) decreased in bilateral frontal and left
      parietal areas, while high alpha power (10-12 Hz) decreased in the left fronto
      parietal areas. CONCLUSIONS: The decrease of the alpha power is as an expression
      of the efficient information transfer within thalamo-cortical pathways. The
      significance of the study stands in the fact that even a very simple STM task
      (only one bit to be memorized) revealed changes in fronto-parietal theta and
      alpha rhythms.

PMID- 14706486
TI  - Neurophysiologic correlates of deficient phonological representations and object
      naming in prematurely born children.
AB  - OBJECTIVE: The aim of this follow-up study was to evaluate the development of
      object naming ability and auditory processing in prematurely born children.
      Furthermore, we investigated whether the mismatch negativity (MMN) parameters at
      the age of 4 years correlate with the MMN parameters and naming ability at the
      age of 6 years. METHODS: Twelve very low birth weight (VLBW) preterm children
      (mean age 5 years 7 months) and matched controls were studied. Object naming was
      measured by the Boston naming test. Auditory event-related potentials (ERPs),
      especially the MMN, were recorded for Finnish syllables (standard /taa/; deviants
      /ta/ and /kaa/) in an oddball paradigm. RESULTS: VLBW preterm children scored
      significantly lower in the object naming test than their controls. The MMN
      amplitude for consonant change was significantly smaller in the preterm group
      compared to the controls. The MMN amplitude at the age of 4 years correlated with
      the MMN amplitude at the age of 6 years. Furthermore, absence of the MMN at the
      age of 4 years predicted naming difficulties at the age of 6 years. CONCLUSIONS:
      VLBW preterm children with a difficulty to preattentively discriminate changes in
      syllables, as indexed by the diminished change detection response, MMN, seem to
      have sustained naming difficulty. Therefore, it is reasonable to record the MMN
      along with the language development from infancy, in order to identify the
      children at risk for language deficiencies and to provide appropriate
      rehabilitation.

PMID- 14706487
TI  - Attention-deficit/hyperactivity disorder: cognitive evoked potential (P300)
      topography predicts treatment response to methylphenidate.
AB  - OBJECTIVE: Auditory cognitive evoked potential (P300) topography predicts robust
      response to the stimulant pemoline in patients with attention
      deficit/hyperactivity disorder (ADHD). Patients with a right fronto-central to
      parietal (FC2:P4) auditory P300 amplitude ratio >0.5 respond robustly to
      pemoline, whereas others do not. This study was performed to demonstrate whether
      the same test and ratio predict treatment response to methylphenidate. METHODS:
      Patients aged 6-12 with DSM-IV diagnosis of ADHD were administered auditory and
      visual cognitive evoked potential (P300) testing. They then underwent single
      blind treatment with an extended-release version of methylphenidate. Robust
      response was defined as a 60% decrease from baseline in a parent rated ADHD
      rating scale. RESULTS: Nine of 20 subjects responded robustly. They did not
      differ from the non-robust responders in age, baseline attention or hyperactivity
      ratings, or any P300 parameter except auditory P300 topography. A FC2:P4 auditory
      P300 amplitude ratio >0.5 predicted robust response with a positive predictive
      value of 0.67 and a negative predictive value of 0.73. CONCLUSIONS: The ratio of
      right fronto-central to parietal auditory P300 amplitude predicts response to
      stimulants in patients with ADHD. As non-stimulant treatments are approved for
      the treatment of ADHD, tests such as this may help pinpoint whether to use a
      stimulant or a medicine with some other mechanism of action.

PMID- 14706488
TI  - Association between quantitative EEG and neurocognition in methamphetamine
      dependent volunteers.
AB  - OBJECTIVE: Exposure to methamphetamine is associated with long-lasting reductions
      in markers for dopaminergic neurons in preclinical models and in humans. These
      changes may be associated with alterations in brain electrical activity and in
      cognition. METHODS: The sample included 9 methamphetamine-dependent subjects and
      10 non-drug-using volunteers. Methamphetamine-dependent subjects were
      hospitalized for 4 days to document abstinence; non-drug-using volunteers were
      studied as outpatients. EEGs were recorded in the eyes-closed resting state, and
      absolute EEG power in each frequency band (0.5-4 Hz, 4-8 Hz, 8-12 Hz, and 12-20
      Hz) was measured using a fast Fourier transform. EEG power was log-transformed
      prior to analysis. Cognition was measured using computerized reaction time tasks.
      RESULTS: Within the methamphetamine-dependent group only, increased theta
      quantitative EEG (QEEG) power correlated significantly with reaction time on
      tasks that were more difficult or that were degraded by fatigue. Increased theta
      QEEG power also correlated with reduced accuracy on a working memory task.
      CONCLUSIONS: Increased QEEG power in the theta band is associated with worse
      performance on reaction time tasks in the methamphetamine-dependent sample but
      not in the non-drug-using volunteers. SIGNIFICANCE: Methamphetamine dependence is
      associated with pathological alterations in brain electrical activity and in
      cognitive performance. QEEG appears to provide a sensitive measure of
      methamphetamine-associated alterations in brain function.

PMID- 14706489
TI  - The time course of the effects of central and peripheral cues on visual
      processing: an event-related potentials study.
AB  - OBJECTIVE: The varying results of visual event-related potential (ERP) studies of
      central and peripheral cueing suggest that these types of cue may modulate
      stimuli processing with different time courses. The aim of this study was to
      investigate differences in the time course of facilitatory effects on the visual
      processing induced by peripheral and central cues. METHODS: ERPs were recorded
      for visual target stimuli that were preceded by informative-central, informative
      peripheral or uninformative-peripheral cues with stimulus onset asynchronies
      (SOAs) of 100, 300, 500 or 700 ms. RESULTS: Validly cued stimuli elicited an
      enhanced P1 component with peripheral cueing at 100 ms SOA. P1 amplitude in valid
      trials was reduced at 300, 500 and 700 ms SOAs with uninformative-peripheral
      cueing, but only at 500 ms SOA with informative-peripheral cueing. With
      informative-central cueing, there was no validity effect on P1. CONCLUSIONS:
      These results suggest that the automatic attraction of attention by a peripheral
      cue results in improved sensory processing at the cued location. This
      facilitation is replaced by an inhibitory effect when SOA increases, although cue
      informativeness may modulate this effect. Central cueing does not affect sensory
      processing at the P1 level.

PMID- 14706490
TI  - Different neuronal contribution to N20 somatosensory evoked potential and to CO2
      laser evoked potentials: an intracerebral recording study.
AB  - OBJECTIVE: To investigate the possible contribution of the primary somatosensory
      area (SI) to pain sensation. METHODS: Depth recordings of CO2 laser evoked
      potentials (LEPs) and somatosensory evoked potentials (SEPs) were performed in an
      epileptic patient with a stereotactically implanted electrode (Talairach
      coordinates y=-23, z=40) that passed about 10 mm below the hand representation in
      her left SI area, as assessed by the source of the N20 SEP component. RESULTS:
      The intracerebral electrode was able to record the N20 SEP component after non
      painful electrical stimulation of her right median nerve. The N20 potential
      showed a phase reversal in the bipolar montage (at about 31 mm from the midline),
      which confirms that the electrode was located near its generator in area 3b. In
      contrast, no reliable response was recorded from the SI electrode after painful
      CO2 laser stimulation of the right hand. An N2-P2 response was evoked at the
      vertex electrode (Cz), thus demonstrating the effectiveness of the delivered CO2
      laser stimuli. CONCLUSIONS: Since the N20 SEP component originates from the
      anterior bank of the post-central gyrus (area 3b), our result suggests that this
      part of SI does not participate in LEP generation. In fact, the previously
      published LEP sources in the SI area estimated from scalp recordings are about 10
      17 mm posterior of the electrode in our patient, suggesting that they are more
      likely located in area 1, 2 or posterior parietal cortex.

PMID- 14706491
TI  - A fast visual evoked potential method for functional assessment and follow-up of
      childhood optic gliomas.
AB  - OBJECTIVE: To evaluate a fast technique of visual evoked potentials (VEPs)
      recording, in response to steady-state luminance stimuli (SS-LVEPs), for
      functional assessment and follow-up of childhood optic gliomas (OGs). METHODS:
      Eighteen OG patients (age range: 3.5-18 years), with different degrees of optic
      pathway damage severity, were examined. Sixteen age-matched normal subjects
      served as controls. Ten of the 18 OG patients were re-tested 1-3 months after the
      first examination. SS-LVEPs were elicited by a sinusoidally-modulated flickering
      (8 Hz) uniform field, generated by a light emitting diode (LED)-array and
      presented monocularly in a mini-ganzfeld. Amplitude and phase of the Fourier
      analyzed response fundamental (1F) and second harmonic (2F) were measured. The
      full VEP protocol had a median duration of 6 min (range: 4-12). RESULTS: When
      compared to normal control values, median 1F and 2F SS-LVEP amplitudes of OG
      patients were reduced (P<0.01), with a borderline increase in 2F phase lag
      (P<0.05). In 11 OG patients with asymmetric optic pathway damage in between-eye
      comparisons, median 1F amplitude losses were greater (P<0.01) in fellow eyes with
      more severe damage. No significant interocular difference was observed in control
      subjects. Median test-retest changes of 1F and 2F component were <20% and 30
      degrees for amplitude and phase, respectively. In individual OG patients, 1F and
      2F amplitudes were positively correlated (P<0.01) with visual acuity. 1F
      amplitude losses were correlated (P=0.01) with the severity of optic disc
      atrophy. Considering both 1F and 2F abnormalities, diagnostic sensitivity of SS
      LVEP in detecting OG-induced optic pathways damage was 83.3%. CONCLUSIONS: The
      present findings support the use of this technique, as an alternative to pattern
      VEPs, for functional assessment and follow-up of OG in uncooperative children.

PMID- 14706493
TI  - Evoked potentials in brain death.

PMID- 14706492
TI  - A novel spatio-temporal decomposition of the EEG: derivation, validation and
      clinical application.
AB  - OBJECTIVE: To obtain clinically useful graphical and numerical data on the
      distribution of activities in the EEG using a novel type of spatio-temporal
      decomposition. METHODS: The EEG is divided into 1/4 s epochs. An approximation to
      the spatial distribution of the locally dominant activity in each epoch is
      represented as a point in a spatial component space. Points representing epochs
      dominated by activity from the same source form a cluster. The centres of these
      clusters represent the global spatial component of each source. As each spatial
      component is identified, its corresponding temporal activity is removed from the
      record, allowing activity from sources with smaller amplitude to become dominant
      in the reduced record. Successive components are identified in the reduced
      record. The method was applied to 40 normal EEGs and features were identified,
      which were common to them all. The method was also applied to 4 separate records
      with different forms of focal abnormality. RESULTS: The method successfully
      separated components from the EEG representing alpha rhythm, eye artefact,
      electrode artefact and EEG. In 40 normal EEGs the method isolated spatial
      components that were common to all EEGs, and in 4 abnormal EEGs it achieved a
      high degree of mutual separation of alpha rhythm, focal spikes, focal theta and
      focal delta activities. CONCLUSIONS: The method achieved a high degree of mutual
      separation of the EEG components and successfully differentiated the artefacts
      due to eye movement, ECG and electrode faults. The clinical implications are
      discussed.

PMID- 14706502
TI  - Prostate cancer. Introduction.

PMID- 14706504
TI  - Use of algorithms as determinants for individual patient decision making:
      national comprehensive cancer network versus artificial neural networks.
AB  - The National Comprehensive Cancer Network (NCCN) developed a series of algorithms
      based on expert opinion to guide the treatment of patients with prostate cancer.
      These algorithms define acceptable treatment options according to the risk of
      disease recurrence and the life expectancy of the patient. However, practicing
      clinicians are expected to use medical judgment when making actual treatment
      decisions. Many clinical and pathologic variables affect patient prognosis,
      which, in turn, influences the treatment and surveillance of patients. Artificial
      neural networks (ANNs) offer promise for improving the predictive value of
      traditional statistical modeling. ANN models have been designed that predict risk
      of lymph node spread and capsular involvement during disease staging, risk of
      disease recurrence after prostatectomy, and overall and cause-specific survival.
      This article provides a review of guidelines, such as NCCN and ANN, used for the
      management of prostate cancer and suggests that group-level recommendations based
      on these algorithms or other decision trees may misrepresent individual patient
      preferences for treatment. Patients and their clinicians need to consider
      available prognostic information, including clinical status, pathologic
      variables, and comorbidities, and then select a reasonable treatment approach
      that maximizes outcome and quality of life according to the preferences of each
      patient.

PMID- 14706503
TI  - Epidemiology of prostate cancer.
AB  - Prostate cancer incidence and mortality rates vary worldwide. In the United
      States, prostate cancer is the most common malignancy affecting men and is the
      second-leading cause of cancer death. Risk of developing prostate cancer is
      associated with advancing age, African American ethnicity, and a positive family
      history, and may be influenced by diet and other factors. The incidence of
      prostate cancer increased sharply after the introduction of widespread screening
      for prostate-specific antigen (PSA), although rates have now returned to levels
      seen before that time. PSA screening has been associated with a shift toward
      diagnosis of earlier-stage disease, but this has not been accompanied by a shift
      toward a lower histologic grade. Although overall prostate cancer mortality rates
      decreased during the 1990s, it was largely because of reductions in deaths among
      men diagnosed with distant disease. In contrast, mortality rates for men
      diagnosed with localized or regional disease increased gradually during most of
      the 1990s before decreasing slightly among white men and reaching plateaus among
      African Americans.

PMID- 14706505
TI  - Evolution of therapeutic approaches with luteinizing hormone-releasing hormone
      agonists in 2003.
AB  - The role of hormone therapy in the current era of widespread testing for prostate
      specific antigen (PSA) continues to evolve. Although still used in patients with
      metastatic disease, the most common uses of luteinizing hormone-releasing hormone
      (LHRH) agonist therapy are in the adjuvant and neoadjuvant settings with
      radiotherapy and sometimes with radical prostatectomy, as well as in the
      treatment of PSA-only recurrence. Immediate (adjuvant) hormone therapy after
      prostatectomy may provide a survival advantage relative to deferred treatment in
      high-risk patients, whereas the survival benefit of adjuvant therapy with
      radiation is clearer. Combined androgen blockade with an LHRH agonist and a
      nonsteroidal antiandrogen provides a very modest but statistically significant
      survival benefit relative to LHRH agonist monotherapy in patients with metastatic
      disease, but it has not been proved in those with less advanced disease.
      Intermittent hormone therapy appears to be effective in maintaining disease
      control for several years, but randomized studies are needed to determine if
      survival is at least equivalent to continuous therapy. Finally, LHRH agonist
      therapy is commonly used in the setting of biochemical or PSA-only recurrence.
      However, there are no randomized controlled trials to prove a survival benefit
      over observation. In summary, hormone therapy now plays a more important role at
      earlier stages of disease, consistent with the changing epidemiology of prostate
      cancer. Additional studies are needed, however, to define how to optimally use
      hormone therapy across various patient types.

PMID- 14706506
TI  - Exploring the effects of luteinizing hormone-releasing hormone agonist therapy on
      bone health: implications in the management of prostate cancer.
AB  - Osteoporosis is a complication that may be associated with long-term androgen
      deprivation therapy (ADT) in men with prostate cancer. Androgen deprivation
      increases bone resorption, thereby leading to a more rapid decrease of bone
      mineral density (BMD) at multiple skeletal sites as compared with age-matched
      healthy men. ADT has been associated with an increased risk of skeletal fracture
      in several retrospective analyses. The role of androgens in maintaining bone
      health appears to be mediated indirectly through their conversion to estrogens,
      although testosterone may be an important factor in bone formation. Physicians
      need to be aware of the potential for osteoporosis and should inform patients of
      appropriate lifestyle and diet modifications, such as calcium and vitamin D
      supplementation, and exercise at the initiation of ADT. Evaluating BMD may become
      the accepted norm. Several studies suggest that bisphosphonates may be beneficial
      in preventing and treating osteoporosis in patients with prostate cancer. The
      overall benefit of ADT in men with prostate cancer will continue to improve as
      potential side effects, such as osteoporosis, are recognized and addressed
      successfully.

PMID- 14706507
TI  - Luteinizing hormone-releasing hormone agonists in the treatment of men with
      prostate cancer: timing, alternatives, and the 1-year implant.
AB  - This article reviews the evidence underlying hormone treatment decisions for men
      with advanced prostate cancer. Luteinizing hormone-releasing hormone (LHRH)
      analogs are the mainstays of therapy, but 3 areas of LHRH use need clarification:
      (1) when to start therapy, (2) what alternatives are available, and (3) how to
      incorporate a long-term strategy for the individual patient. The Medical Research
      Council (MRC) study, a randomized clinical trial in 938 patients, shows that
      immediate hormone therapy in men presenting with advanced prostate cancer (stage
      > or =T3) imparts a survival advantage over a delayed-treatment approach (7.5
      years vs 5.8 years, P = 0.0003). LHRH analogs are also widely used (1) along with
      definitive radiation therapy, (2) when positive lymph nodes are found after
      radical prostatectomy, and (3) when prostate-specific antigen increases after any
      primary treatment (biochemical failure). In these situations, timing of therapy
      is somewhat controversial. Several new developments in hormone therapy are
      noteworthy, including high-dose antiandrogen monotherapy, a LHRH antagonist
      (abarelix), transdermal estrogens, and a subcutaneous implant that releases
      leuprolide acetate at a constant rate for 1 year (Viadur; Bayer Corporation, West
      Haven, CT). With 4 years of clinical experience with Viadur now available, the
      long-term data indicate continued, uniform testosterone suppression into the
      castrate range and a high degree of patient satisfaction. Thus, a long-term
      strategy-permitting increased patient freedom and decreased dependence on a fixed
      injection schedule-has for the first time become possible with the Viadur implant
      in men requiring hormone therapy for prostate cancer.

PMID- 14706508
TI  - Early days of mammalian somatic cell genetics: the beginning of experimental
      mutagenesis.

PMID- 14706509
TI  - Molecular aspects of epithelial cell plasticity: implications for local tumor
      invasion and metastasis.
AB  - Carcinomas arising from epithelial cells represent the most prevalent
      malignancies in humans, and metastasis is the major cause for the death of
      carcinoma patients. The breakdown of epithelial cell homeostasis leading to
      aggressive cancer progression has been correlated with the loss of epithelial
      characteristics and the acquisition of a migratory phenotype. This phenomenon,
      referred to as epithelial to mesenchymal transition (EMT), is considered as a
      crucial event in late stage tumorigenesis. Here we summarize the multitude of EMT
      models derived from different tissues, and review the diversity of molecular
      mechanisms contributing to the plasticity of epithelial cells. In particular, the
      synergism between activation of Ras, provided by the aberrant stimulation of
      receptor tyrosine kinases, and transforming growth factor (TGF)-beta signaling
      plays a pivotal role in inducing EMT of various epithelial cell types. Cytokines
      such as TGF-beta and extracellular matrix molecules are thought to fundamentally
      contribute to the microenvironmental interaction between stromal and malignant
      cells, and provide the basis for a broad repertoire of epithelial
      differentiation. Investigations of EMT tumor models, which represent in vitro
      correlates to local invasion and metastasis in vivo, facilitate the
      identification of diagnostic markers for a more accurate and faithful clinical
      and pathological assessment of epithelial tumors. In addition, the analysis of
      molecular mechanisms involved in EMT might yield novel therapeutic targets for
      the specific treatment of aggressive carcinomas.

PMID- 14706510
TI  - Cytogenetic analysis and occupational health in the Czech Republic.
AB  - This paper summarizes the experiences of the Czech Hygiene Service since the
      middle 1970s until the present time, using cytogenetic analysis as a biomarker of
      exposure. We have included a review of all the available scientific literature in
      Czech as well as in English, and have described the most important milestones in
      the history of the use of cytogenetic analysis in the Czech Republic. Details on
      the levels of occupational exposure and the corresponding observed frequencies of
      aberrant cells are provided. Furthermore, we discuss the interpretation of the
      cytogenetic findings in the context of occupational health and give several
      examples when the results of cytogenetic analysis provided the chief argument
      used to enforce improved working conditions and to establish safer maximum
      allowable concentrations.

PMID- 14706511
TI  - The second National Toxicology Program comparative exercise on the prediction of
      rodent carcinogenicity: definitive results.
AB  - Chemical carcinogenicity has been the target of a large array of attempts to
      create alternative predictive models, ranging from short-term biological assays
      (e.g. mutagenicity tests) to theoretical models. Among the theoretical models,
      the application of the science of structure-activity relationships (SAR) has
      earned special prominence. A crucial element is the independent evaluation of the
      predictive ability. In the past decade, there have been two fundamental
      comparative exercises on the prediction of chemical carcinogenicity, held under
      the aegis to the US National Toxicology Program (NTP). In both exercises, the
      predictions were published before the animal data were known, thus using a most
      stringent criterion of predictivity. We analyzed the results of the first
      comparative exercise in a previous paper [Mutat. Res. 387 (1997) 35]; here, we
      present the complete results of the second exercise, and we analyze and compare
      the prediction sets. The range of accuracy values was quite large: the systems
      that performed best in this prediction exercise were in the range 60-65%
      accuracy. They included various human experts approaches (e.g. Oncologic) and
      biologically based approaches (e.g. the experimental transformation assay in
      Syrian hamster embryo (SHE) cells). The main difficulty for the structure
      activity relationship-based approaches was the discrimination between real
      carcinogens, and non-carcinogens containing structural alerts (SA) for genotoxic
      carcinogenicity. It is shown that the use of quantitative structure-activity
      relationship models, when possible, can contribute to overcome the above problem.
      Overall, given the uncertainty linked to the predictions, the predictions for the
      individual chemicals cannot be taken at face value; however, the general level of
      knowledge available today (especially for genotoxic carcinogens) allows qualified
      human experts to operate a very efficient priority setting of large sets of
      chemicals.

PMID- 14706512
TI  - Photochemical genotoxicity: principles and test methods. Report of a GUM task
      force.
AB  - In recent years, assessing the photogenotoxic potential of a compound became an
      issue for certain drugs and cosmetical products. Therefore, existing methods
      performed according to international guidelines (e.g. OECD guidelines) were
      adapted to the use of concurrent UV-visible (UV-Vis) light irradiation for the
      assessment of photomutagenicity/photogenotoxicity. In this review,
      photobiological bases of the processes occurring in the cell after irradiation
      with UV- and/or visible (vis)-light as well as a compilation of testing methods
      is presented. Methods comprise cell free investigations on naked DNA and in vitro
      methods, such as the photo-Ames test, the photo-HPRT/photo-mouse lymphoma assay
      (MLA), the photo-micronucleus test (MNT), the photo-chromosomal aberration test
      (CA) and the photo-Comet assay. A compilation of the currently available
      international literature of compounds tested on photogenotoxicity is given for
      each method. The state of the art of photogenotoxicity testing as well as the
      rational for testing are outlined in relation to the recommendations reached in
      expert working groups at different international meetings and to regulatory
      guidance papers. Finally, photogenotoxicity testing as predictor of
      photocarcinogenicity and in the light of risk assessment is discussed.

PMID- 14706513
TI  - Genotoxicity of microcystin-LR in human lymphoblastoid TK6 cells.
AB  - Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem
      in several industrialized areas of the world. Microcystin-LR (MCLR) is a cyclic
      heptapeptidic toxin produced by the cyanobacteria. In the present study, we used
      human lymphoblastoid cell line TK6 to investigate the in vitro genotoxicity of
      MCLR. In a standard 4h treatment, MCLR did not induce a significant cytotoxic
      response at <80 microg/ml. In a prolonged 24h treatment, in contrast, it induced
      cytotoxic as well as mutagenic responses concentration-dependently starting at 20
      microg/ml. At the maximum concentration (80 microg/ml), the micronucleus
      frequency and the mutation frequency at the heterozygous thymidine kinase (TK)
      locus were approximately five-times the control values. Molecular analysis of the
      TK mutants revealed that MCLR specifically induced loss of heterozygosity at the
      TK locus, but not point mutations or other small structural changes. These
      results indicate that MCLR had a clastogenic effect. We discuss the mechanisms of
      MCLR genotoxicity and the possibility of its being a hepatocarcinogen.

PMID- 14706514
TI  - Urinary 1-hydroxypyrene and mutagenicity in bus drivers and mail carriers exposed
      to urban air pollution in Denmark.
AB  - BACKGROUND: Previous studies in Denmark have shown that bus drivers and tramway
      employees were at an increased risk for developing several types of cancer and
      that bus drives from central Copenhagen have high levels of biomarkers of DNA
      damage. AIMS: The present study evaluates 1-hydroxypyrene concentrations and
      mutagenic activity in urine as biomarkers of exposure in non-smoking bus drivers
      in city and rural areas on a work day and a day off and in non-smoking mail
      carriers working outdoors (in the streets) and indoors (in the office). METHODS:
      Twenty-four hour urine samples were collected on a working day and a day off from
      60 non-smoking bus drivers in city and rural areas and from 88 non-smoking mail
      carriers working outdoors (in the streets) and indoors (in the office). The
      concentration of 1-hydroxypyrene was measured by means of HPLC and the mutagenic
      activity was assessed by the Ames assay with Salmonella tester strain YG1021 and
      S9 mix. The N-acetyltransferase (NAT2) phenotype was used as a biomarker for
      susceptibility to mutagenic/carcinogenic compounds. RESULTS: Bus drivers excreted
      more 1-hydroxypyrene in urine than did mail carriers. The differences were
      slightly smaller when NAT2 phenotype, cooking at home, exposure to vehicle
      exhaust, and performing physical exercise after work were included. The NAT2 slow
      acetylators had 29% (1.29 [CI: 1.15-1.98]) higher 1-hydroxypyrene concentrations
      in urine than the fast acetylators. Male bus drivers had 0.92 revertants/mol
      creatinine [CI: 0.37-1.47] and female bus drivers 1.90 revertants/mol creatinine
      [CI: 1.01-2.79] higher mutagenic activity in urine than mail carriers.
      CONCLUSION: The present study indicates that bus drivers are more exposed to
      polycyclic aromatic hydrocarbons (PAH) and mutagens than mail carriers. Mail
      carriers who worked outdoors had higher urinary concentration of 1-hydroxypyrene,
      a marker of exposure to PAH, than those working indoors. The individual levels of
      urinary mutagenic activity were not correlated to excretion of 1-hydroxypyrene.
      This might be due to the fact that the most potent mutagenic compounds in diesel
      exhaust are not PAH but dinitro-pyrenes. Among bus drivers, fast NAT2 acetylators
      had higher mutagenic activity in urine than slow NAT2 acetylators and female bus
      drivers had higher mutagenic activity than male bus drivers.

PMID- 14706515
TI  - Ochratoxin A and zearalenone: a comparative study on genotoxic effects and cell
      death induced in bovine lymphocytes.
AB  - Ochratoxin A (OTA) and zearalenone (ZEA), two naturally occurring contaminants of
      animal feed, have been implicated in several mycotoxicoses in farm livestock but
      there is little information on their genotoxicity and toxicity in these species.
      Therefore, we investigated on the cytogenetic and cytotoxic effects of both OTA
      and ZEA in in vitro cultures of bovine lymphocytes. We determined chromosome
      aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic
      index (MI) and cell viability following OTA and ZEA treatment. This report is the
      first to provide evidence of a statistically significant increase of structural
      CAs and of SCEs/cell associated with a reduction of the MI in all OTA- and ZEA
      treated bovine lymphocyte cultures and a clear reproducible reducing effect of
      OTA on cell viability mediated by enhanced apoptosis. OTA-induced programmed cell
      death was not limited to bovine lymphocytes, as comparable data were demonstrated
      in the human leukemic T-cell line Jurkat.

PMID- 14706516
TI  - Adenomatous polyposis coli truncation mutations in 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP)-induced intestinal tumours of multiple
      intestinal neoplasia mice.
AB  - The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
      induces intestinal tumours in C57BL/6J-multiple intestinal neoplasia (Min)/+
      mice. The main mechanism for PhIP-induced tumour induction in Min/+ mice is loss
      of the wild-type adenomatous polyposis coli (Apc) allele, i.e. loss of
      heterozygosity (LOH). In this study, single injections of either 10, 17.5 or 25
      mg/kg PhIP on days 3-6 after birth all increased the mean number of small
      intestinal tumours two to three-fold, from 37.7 in controls to 124.8 in the PhIP
      treated Min/+ mice. In total, we analysed 292 small intestinal tumours and 253 of
      these had LOH. The frequency of LOH in the Apc gene was 88, 93, 83 and 84% in
      tumours of 0, 10, 17.5 and 25 mg/kg PhIP-treated mice, respectively. Therefore,
      these lower doses of PhIP did not reduce the frequency of LOH, as found in our
      previous study with a single injection of 50 mg/kg PhIP (Mutat. Res. 1-2 (2002)
      157). In the second part of this study, we wanted to characterise Apc truncation
      mutations from tumour samples apparently retaining the Apc wild-type allele from
      this and two previous experiments with PhIP-exposed Min/+ mice. In the first half
      of exon 15 in Apc, we verified 25 mutations from 804 tumour samples of PhIP
      treated mice. Of these were 60% G-->T transversions, and 16% G deletions,
      indicating that these are the predominant types of PhIP-induced truncation
      mutations in the Apc gene in Min/+ mice. Most of the mutations were located
      between codon 989 and 1156 corresponding to the first part of the beta-catenin
      binding region. We also identified two Apc truncation mutations from 606
      spontaneously formed intestinal tumours from untreated Min/+ mice, one C-->T
      transition and one T insertion, which were different from those induced by PhIP.

PMID- 14706517
TI  - Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors
      associated with cellular response to DNA damage.
AB  - Ataxia telangiectasia mutated (ATM) is the gene mutated in the genetic disorder
      ataxia telangiectasia (AT), the symptoms of which include sensitivity to
      radiation and an increased risk of cancer. ATM is a kinase involved in activating
      the appropriate damage-response pathway, leading to either cell-cycle arrest or
      apoptosis, and is therefore a key checkpoint molecule in regulating cell-cycle
      response to DNA damage and responsible for maintenance of genome integrity.
      However, little is known about the association of ATM mutations with human
      gastric cancer (HGC). In order to determine the mutation and mRNA expression
      changes of the ATM gene in HGC, we performed analyses by denaturing high
      performance liquid chromatography (DHPLC), DNA sequencing and RT-PCR technique on
      13 human gastric tumor cell lines and 30 cases of fresh tumor specimens matched
      normal tissue. We compared the potential effect of the ATM gene mutation and cell
      behavior including cell-cycle arrest and induction of apoptosis in the tumor cell
      lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure. Our
      data show that frequent variations were observed at 10 exons and 2 cDNA fragments
      which covered 8 other exons of the ATM gene as 5 out of 13 on the cell lines
      (38.5%) and 2 out of 30 cases in the tissue specimens (6.7%). All point mutations
      were confirmed as base substitutions (5982T-C; 6620A-G; 8684G-G/A; 9389C-G) and
      deletions (1079delC) by use of DNA sequencing. Among the mutations, one was
      reported previously in breast cancer, the other five have not yet been reported.
      The expression of ATM was significantly lower in five cell lines (MGC803; MKN45;
      SGC7901; GES and SUN-1) than in two others (BGC823 and RF48). G2/M cell-cycle
      arrest and apoptosis were observed in ATM-deficient MGC803 cells challenged with
      IR. A transient up-regulation of p53 occurred 1h post-IR in BGC823 cells but not
      in MGC803 cells. Our findings suggest that ATM mutations might be a pathogenic
      factor for an increased risk of gastric cancer, and the dysfunction of ATM may
      lead to a hypersensitivity to ionizing radiation in gastric cancer cells,
      possibly by a p53-dependent pathway.

PMID- 14706518
TI  - Evaluation of the genotoxicity of four herbicides in the wing spot test of
      Drosophila melanogaster using two different strains.
AB  - In the present study, the herbicides bentazone, molinate, thiobencarb and
      trifluralin were evaluated for mutagenic and recombinagenic effects using the
      wing spot test of Drosophila melanogaster (somatic mutation and recombination
      test, SMART). Both standard (ST) and high-bioactivation (HB) fly crosses were
      used, the latter cross is characterised by a high sensitivity to promutagens and
      procarcinogens. Three-day-old larvae, transheterozygous for the multiple wing
      hairs (mwh, 3-0.3) and flare-3 (flr(3), 3-38.8) genes, were chronically fed with
      six different concentrations of each herbicide. Feeding ended with pupation of
      the surviving larvae and the genetic changes induced in somatic cells of the
      wing's imaginal discs lead to the formation of mutant clones on the wing blade.
      Point mutation, chromosome breakage and mitotic recombination produce single
      spots; while twin spots are produced only by mitotic recombination. Bentazone,
      usually considered as a non-mutagen, gave positive results in the wing spot test
      with the high-bioactivation cross. Molinate, about which information on mutagenic
      effects is inconclusive, gave positive responses in both the standard and the
      high-bioactivation crosses, while the other thiocarbamate, thiobencarb, gave
      positive results only in the standard cross and at the highest concentration
      tested (10 mM). Finally, trifluralin, one of the most widely studied herbicides
      for genotoxic effects, gave positive results in the wing spot test with both
      crosses. Apart from the interest of the results found in the genotoxic evaluation
      of the four selected herbicides, our results also contribute to extend the
      existing database on the Drosophila wing spot test, and corroborate the utility
      of the use of high-bioactivation strains for the genotoxic evaluation of
      xenobiotics.

PMID- 14706519
TI  - Non-thermal effects of power-line magnetic fields (50 Hz) on gene expression
      levels of pluripotent embryonic stem cells-the role of tumour suppressor p53.
AB  - The diffusion of extremely low-frequency (50 Hz) electromagnetic fields (ELF-EMF)
      in the human environment raises the question of the induction of biological
      effects of EMF on mammalian cells. We used the model of mouse pluripotent
      embryonic stem (ES) cells, which have the capacity to develop in vitro into cells
      of all lineages, to analyse non-thermal effects of ELF-EMF. Wild type (wt) and
      p53-deficient ES cells were exposed under controlled conditions to ELF-EMF
      signals simulating power-line (50 Hz) magnetic field (PL-MF) exposure. Different
      flux densities of 0.1 mT, 1.0 mT or 2.3 mT and intermittency schemes with various
      ON/OFF cycles were applied for 6 h or 48 h during the first stages of cell
      differentiation. Transcript levels of regulatory genes, such as egr-1, p21, c
      jun, c-myc, hsp70 and bcl-2, were analysed by semi-quantitative RT-PCR
      immediately after exposure or after a recovery time of 18 h. Intermittent PL-MF
      exposure to 5 min ON/30 min OFF cycles at a flux density of 2.3 mT for 6 h
      resulted in a significant up-regulation of c-jun, p21 and egr-1 mRNA levels in
      p53-deficient, but not in wild-type cells. No significant effects were observed
      in both cell systems by PL-MF at lower flux densities, longer exposure time or
      after 18 h recovery time. Our data indicate that 5 min ON/30 min OFF intermittent
      PL-MF exposure is capable of evoking non-thermal responses in ES cells, dependent
      on the cellular p53 function. The nature of the biological responses triggered by
      PL-MF is discussed.

PMID- 14706520
TI  - Ginseng reduces the micronuclei yield in lymphocytes after irradiation.
AB  - To assess the effect of Chinese ginseng in modifying the radiation-induced
      micronuclei (MN) yield in human G(o) peripheral blood lymphocytes (PBL), we
      conducted the cytokinesis-blocked (CB) MN assay in blood samples obtained from
      healthy volunteers (n=4). Before (137)Cs ex vivo irradiation, mononuclear cell
      cultures from each sample were incubated 24 h with different concentrations (0
      2000 microg ml(-1)) of crude water extract of ginseng dry root. We found that (1)
      at 0 Gy and without the presence of ginseng, MN yield (mean+/-S.E.M.) was 11.7+/
      2.7 per 1000 binucleated (BN) cells. Different concentrations of ginseng crude
      water extract did not affect the MN yields and the proliferative activity of PBL;
      (2) after 1 and 2 Gy exposure, radiation alone sharply increased the MN yields,
      respectively, to 119.6+/-17.4 and 340.5+/-20.9 per 1000 BN cells. However,
      treatment with ginseng for 24 h before radiation exposure, resulted in a
      significant linear decline of MN yields as ginseng concentration increases.
      Compared to radiation alone, the extent to which ginseng water extract reduced
      the MN yields induced by 1 Gy exposure was 46.0% at 1500 microg ml(-1) and 61.5%
      at 2000 microg ml(-1), and with 2 Gy exposure, it was 38.6% at 1500 microg ml(-1)
      and 46.5% at 2000 microg ml(-1); (3) MN data suggested a tendency for
      overdispersion relative to the Poisson model; and (4) over the different levels
      of ginseng concentrations, the trend in micronucleated BN index was as similar as
      that of the MN yields. These results indicated that (1) ginseng crude water
      extract exerts no apparent cytogentic effect on human PBL at concentrations up to
      2000 microg ml(-1) as evaluated by the CBMN assay; and (2) the protection of
      ginseng water extract against (137)Cs-induced MN in human PBL is concentration
      dependence. Therefore, our findings indicated that ginseng may have therapeutic
      value as a possible radioprotector for normal tissue during radiotherapy of
      cancer patients.

PMID- 14706521
TI  - Genotoxicity studies with pure trans-capsaicin.
AB  - Both positive and negative effects have been found in classical genetic
      toxicology assays with capsaicin. However, the capsaicin tested in most studies
      has been derived from pepper plant extracts, which is likely to display varying
      degrees of purity and possibly diverse impurity profiles. Therefore, the
      objective of the series of studies reported here was to test the genotoxic
      potential of pure, synthetic trans-capsaicin (the only naturally occurring
      geometric isomer of capsaicin), using four genotoxicity assays widely used to
      evaluate drug substances. These included the Ames, mouse lymphoma cell mutation,
      mouse in vivo bone marrow micronucleus and chromosomal aberration in human
      peripheral blood lymphocytes (HPBL) assays. In the Ames assay, pure trans
      capsaicin was not mutagenic to Salmonella typhimurium or Escherichia coli when
      dissolved in dimethylsulfoxide and tested at concentrations extending into the
      toxic range. trans-Capsaicin was weakly mutagenic in mouse lymphoma L5178Y cells,
      in the presence of S9 mix, when dissolved in dimethylsulfoxide and tested at
      concentrations extending into the toxic range. Limited evidence for very weak
      activity was also obtained in the absence of S9 mix. trans-Capsaicin did not
      induce micronuclei in bone marrow cells when tested to the maximum tolerated dose
      of 800 mg/kg per day in male and 200 mg/kg per day in female CD-1 mice using a 0
      h plus 24 h oral dosing and 48 h sampling regimen. Finally, trans-capsaicin did
      not induce structural or numerical chromosomal aberrations when evaluated for its
      ability to induce clastogenicity in blood lymphocytes. Taken together, these data
      suggest that the genotoxic potential of pure trans-capsaicin is very low,
      especially as the clinical significance of weak mutagenicity in the mouse
      lymphoma assay for catechol-moiety containing compounds is unclear. Moreover, the
      different genotoxicity profiles of pure trans-capsaicin and purified chili pepper
      extracts suggest that the purity and source of capsaicin should always be an
      important consideration for toxicological evaluations.

PMID- 14706523
TI  - Invertebrate neuropeptides IV. Special issue dedicated to Dr. Hugo Arechiga.

PMID- 14706522
TI  - Photomutagenicity of 16 polycyclic aromatic hydrocarbons from the US EPA priority
      pollutant list.
AB  - The photomutagenicity of 16 polycyclic aromatic hydrocarbons (PAHs), all on the
      United States Environmental Protection Agency (US EPA) priority pollutant list,
      was studied. Concomitant exposing the Salmonella typhimurium bacteria strain
      TA102 to one of the PAHs and light (1.1 J/cm2 UVA+2.1 J/cm2 visible) without the
      activation enzyme S9, strong photomutagenic response is observed for anthracene,
      benz[a]anthracene, benzo[ghi]perylene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene,
      and pyrene. Under the same conditions, acenaphthene, acenaphthylene,
      benzo[k]fluoranthene, chrysene, and fluorene are weakly photomutagenic.
      Benzo[b]fluoranthene, fluoranthene, naphthalene, phenanthrene, and
      dibenz[a,h]anthracene are not photomutagenic. These results indicate that PAHs
      can be activated by light and become mutagenic in Salmonella TA102 bacteria. At
      the same time, the mutagenicity for all the 16 PAHs was examined with the
      standard mutagenicity test with 10% S9 as the activation system.
      Benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, acenaphthylene, and
      fluorene are weakly mutagenic, while the rest of the PAHs are not. In general,
      the photomutagenicity of PAHs in TA102 does not correlate with their S9-activated
      mutagenicity in either TA102 or TA98/TA100 since they involve different
      activation mechanisms.

PMID- 14706524
TI  - Neuropeptides in perisympathetic organs of Manduca sexta: specific composition
      and changes during the development.
AB  - We used a combination of matrix-assisted laser desorption-ionization time-of
      flight mass spectrometry and immunocytochemistry to investigate the peptides from
      abdominal perisympathetic organs of Manduca sexta. Altogether three mass peaks,
      detected in mass spectra from single abdominal perisympathetic organs were
      identical with already known neuropeptides, namely CAP(2b), CCAP, and Manduca
      allatotropin. Only CAP(2b) was found throughout the postembryonic development. In
      larvae, perisympathetic organs of the abdominal ganglia 1 and 7 do not accumulate
      neuropeptides. During the metamorphosis, the number of putative hormones stored
      in the abdominal perisympathetic organs, increases dramatically. Not a single
      substance, however, obtained in mass spectra of larval perisympathetic organs
      disappeared in the respective adult neurohemal organs. Peptides from abdominal
      perisympathetic organs are different from those of thoracic perisympathetic
      organs and the retrocerebral complex. Manduca-FLRFa-2 and -3 are enriched in
      thoracic perisympathetic organs; FLRFa-1, corazonin and adipokinetic hormone are
      abundant peptides of the retrocerebral complex. The majority of ion signals,
      however, represent unknown substances. An antiserum which recognized CAP(2b)
      allowed the morphological characterization of a median neurosecretory system in
      the abdominal ventral nerve cord of M. sexta, which resembles that of cockroach
      embryos. Double stainings confirmed that crustacean cardioactive peptide (CCAP)
      becomes colocalized with CAP(2b) in median neurosecretory cells during the last
      larval instar. This colocalization continues in adult insects.

PMID- 14706525
TI  - Identification of neuropeptides from brains of larval Manduca sexta and Lacanobia
      oleracea using MALDI-TOF mass spectrometry and post-source decay.
AB  - The occurrence of neuropeptides in the brain of larvae of the tobacco hawkmoth,
      Manduca sexta, and tomato moth, Lacanobia oleracea, was investigated using matrix
      assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry
      (MS) and post-source decay (PSD). Methanolic extracts of 100 brains separated by
      reversed-phase high performance liquid chromatography yielded numerous ion peaks,
      some of which were common to both species. In M. sexta six [M+H](+) ions were in
      agreement with peptides previously structurally characterised from M. sexta (FLRF
      amides I, II and III, M. sexta allatostatin, CAP(2b) and myoinhibitory peptide
      VI), whereas a further five corresponded to other known lepidopteran peptides
      (cydiastatins 3 and 4, helicostatins 1 and 6 and helicokinin II). Of these the
      identities of FLRF-amide I, cydiastatins 3 and 4 and CAP(2b) were confirmed by
      PSD analysis. Fourteen [M+H](+) ions corresponding to known lepidopteran peptides
      (FLRF-amide I, cydiastatins 2, 3 and 4, helicostatins 1, 5, 6, 7 and 9, CCAP,
      CAP(2b), M. sexta allatostatin and myoinhibitory peptide VI) were measured in L.
      oleracea brain extracts. From this insect, cydiastatins 3 and 4, helicostatin 5
      and FLRF-amide I were identified by PSD. These peptides had not previously been
      structurally characterised from L. oleracea.

PMID- 14706526
TI  - Peptide profiling of a single Locusta migratoria corpus cardiacum by nano-LC
      tandem mass spectrometry.
AB  - The pars intercerebralis-corpora cardiaca complex in insects is the functional
      equivalent of the vertebrate brain-pituitary axis. During the past few decades
      more than 40 neuropeptides have been isolated from the locust brain-corpus
      cardiacum complex. Tedious and time-consuming successive purification rounds of
      large tissue extracts were necessary to achieve the purification and sequencing
      of most of these signal molecules. Nowadays, the combination of nanoscale liquid
      chromatography and the very sensitive tandem mass spectrometry allows us to
      identify and sequence peptides in very low concentration directly from tissue
      extracts. In this manuscript, we review previous data on the peptidome analysis
      of the locust corpora cardiaca, with emphasis on AKH processing. In addition, we
      report the peptide profiling of a single corpus cardiacum from Locusta
      migratoria. 23 peptides were isolated and sequenced in a single nano-LC-MS/MS
      experiment, demonstrating the sensitivity and effectiveness of mass spectrometry
      in peptide research.

PMID- 14706527
TI  - Mass spectrometric analysis of putative capa-gene products in Musca domestica and
      Neobellieria bullata.
AB  - Neuropeptides of the capa-gene are typical of the abdominal neurosecretory system
      of insects. In this study, we investigated these peptides in two widely
      distributed and large pest flies, namely Musca domestica and Neobellieria
      bullata. Using a combination of MALDI-TOF and ESI-QTOF mass spectrometry,
      periviscerokinins and a pyrokinin were analyzed from single perisympathetic organ
      preparations. The species-specific peptide sequences differ remarkably between
      the related dipteran species. These differences could make it possible to develop
      peptide-analogs with group- or species-specific efficacy.

PMID- 14706528
TI  - Peptidomics of the locust corpora allata: identification of novel pyrokinins (
      FXPRLamides).
AB  - The peptidomes of the corpora allata of Locusta migratoria and Schistocerca
      gregaria were investigated by both matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) and nanoscale liquid
      chromatography quadrupole time-of-flight tandem mass spectrometry (nanoLC-Q-TOF
      MSMS). The pyrokinin (-FXPRLamide) family seems to be predominant. In addition to
      the known pyrokinins, we de novo sequenced four pyrokinins in L. migratoria and
      five in S. gregaria. In addition, one pyrokinin-like peptide (-PRLamide) was
      identified in S. gregaria. Besides the -(FX)PRLamides, FLRFamide-1, the
      allatostatins (A family) and numerous as yet unidentified peptides are also
      present in the corpora allata.

PMID- 14706529
TI  - Localization and physiological effects of RFamides in the corpora allata of the
      cockroach Diploptera punctata in relation to allatostatins.
AB  - The distribution of FMRFamide immunoreactivity in the brain-retrocerebral complex
      of adult female Diploptera punctata was examined. Immunoreactivity was observed
      in the brain and corpus allatum as well as in the corpus cardiacum.
      Immunoreactivity co-localized with allatostatin immunoreactivity within several
      lateral neurosecretory cells of the brain and in their endings within the corpus
      allatum. By in vitro radiochemical assay of juvenile hormone release, the effect
      of two native D. punctata RFamides, an FLRFamide (Leucomyosuppressin) and an
      FIRFamide were examined. The latter, for which the sequence (SKPANFIRFamide) is
      reported here, stimulated juvenile hormone release but acted only on corpora
      allata from females at the end of vitellogenesis (day 6). The interaction of
      these two RFamides and three D. punctata allatostatins, Dippu-AST 2, 5, and 7
      were similarly examined. Only Dippu-AST 2 stimulated release of RFamides from the
      corpora allata and only on day 6 whereas both RFamides were able to attenuate the
      inhibitory activity of Dippu-AST 2.

PMID- 14706530
TI  - FMRFamide-related peptides in the gut of Locusta migratoria L.: a comprehensive
      map and developmental profile.
AB  - The gut tissues and associated nervous system of the African migratory locust,
      Locusta migratoria, were found to contain FMRFamide-like immunoreactive (FLI)
      material throughout the five larval instars and 2 weeks into the adult stage in
      both males and females. FMRFamide-like immunoreactivity associated with the
      locust gut was described using camera lucida techniques. FMRFamide-like
      immunoreactivity is observed in the frontal connectives, recurrent nerve, and
      oesophageal nerves; projections from the ingluvial ganglion onto the anterior
      midgut, and from the proctodeal nerve onto the hindgut and posterior midgut; in
      the neuropils of the frontal ganglion, hypocerebral ganglion and ingluvial
      ganglia; 30 cell bodies in the frontal ganglion; multipolar sensory cells on the
      foregut; and endocrine-like cells in the gastric caecae and midgut.
      Radioimmunoassay (RIA) was used to determine the quantities of FLI material in
      foreguts, gastric caecae, anterior and posterior midguts, and hindgut of first
      fifth instar larvae, 1-3- and 14-17-day male and female adult locusts. As
      expected, as the tissue size (assessed by total protein content) increases, so
      does the amount of FLI material in each tissue. Normalizing for tissue size
      reveals significant differences in FLI content among the stages for each tissue
      tested. Reversed phase-high pressure liquid chromatography (RP-HPLC) followed by
      RIA has identified four groups of FLI fractions present in the gut, and different
      members of these groups are present in the various gut tissues.

PMID- 14706531
TI  - Role of FMRFamide in the reproduction of Octopus vulgaris: molecular analysis and
      effect on visual input.
AB  - As a part of continuous research on the neurobiology of the cephalopods in
      general, and the neuroendocrine control of reproduction in Octopus vulgaris in
      particular, the presence, the molecular analysis and the effect of FMRFamide on
      the screening-pigment migration in the visual system have been analysed.
      FMRFamide immunoreactive fibres are present in the outer plexiform layer of the
      retina as well as in the plexiform zone of the deep retina. These fibres
      presumably come from optic and olfactory lobes. We isolated an incomplete Octopus
      FMRFamide cDNA which encodes an amino terminal truncated precursor containing
      several FMRFamide-related peptides (FaRPs) showing a high degree of identity with
      the FaRPs encoded in the precursor of Sepia officinalis, except for the presence
      of an Rpamide related peptide, present only in cnidarians. Finally, stimulation
      of isolated retina demonstrated that the effect of this tetrapeptide, coupled
      with dopamine, is the induction of an extreme adaptation of the retina to the
      light condition. This situation de facto inhibits sexual maturation. Our results
      on the effect of FMRFamide on the retina confirm the suggested hypothesis that
      this peptide plays an inhibitory role on the activity of optic gland.

PMID- 14706532
TI  - Distribution and function of an Aplysia cardioexcitatory peptide, NdWFamide, in
      pulmonate snails.
AB  - The distribution and function of an Aplysia cardioexcitatory peptide, NdWFamide,
      were examined in the nervous system of pulmonate snails. We chemically identified
      the authentic NdWFamide from a land snail (Euhadra congenita) and a freshwater
      snail (Lymnaea stagnalis). NdWFamide potentiated the heartbeat of those snails.
      Immunohistochemistry using anti-NdWFamide antibody demonstrated the distribution
      of NdWFamide-containing neurons and fibers in the central nervous system, as well
      as peripheral tissues, such as the cardiovascular region and accessory sex
      organs. These results suggest that NdWFamide is a neuropeptide mediating the
      neural regulation of the activity of the cardiovascular and reproductive systems
      of snails.

PMID- 14706533
TI  - Lipid metabolism in the cockroach, Periplaneta americana, is activated by the
      hypertrehalosemic peptide, HTH-I.
AB  - Phosphatidylcholine and phosphatidylethanolamine are the major constituents of
      the phospholipid pool in cockroach (Periplaneta americana) fat body and
      hemolymph. Both species of phospholipid are significantly decreased 6h after
      injecting hypertrehalosemic hormone I (HTH-I) into the hemocoel. Loss of
      phospholipid is accompanied by an accumulation of the phospholipid degradation
      products glycerophosphorylcholine and glycerol. HTH-I also increases
      phospholipase activity in the hemolymph and this is thought to be responsible for
      the depletion of hemolymph phospholipid. Phospholipase activity peaks
      approximately 2h after injection of HTH-I and returns to normal at 6h. In vitro,
      total phospholipid in the fat body is decreased by HTH-I whereas the
      concentration of diacylglycerol displays a corresponding increase. HTH-I elevates
      free fatty acid levels but has no effect on triacylglycerol. These effects of HTH
      I are blocked by the phospholipase inhibitor mepacrine.

PMID- 14706534
TI  - The distribution and effects of Dippu-allatostatin-like peptides in the blood
      feeding bug, Rhodnius prolixus.
AB  - Using a polyclonal antiserum to Dippu-allatostatin 7 (Dippu-AST 7; formerly AST
      1) of the cockroach Diploptera punctata, we have demonstrated the presence of AST
      like immunoreactivity (ALI) in cells and processes throughout the nervous system,
      gut, and peripheral tissues of unfed fifth instar and adult Rhodnius prolixus.
      ALI in apparent neurosecretory cells of the brain, suboesophageal ganglion, and
      mesothoracic ganglionic mass, as well as in midgut endocrine cells, suggests that
      Rhodnius allatostatins may act as neurohormones/hormones. The presence of ALI in
      possible interneurons and areas of neuropile throughout the CNS also suggests
      roles as neuromodulators and/or neurotransmitters. Dippu-AST 7 inhibits
      spontaneous and leucokinin 1 (LK 1)-induced contractions of the Rhodnius hindgut
      in a dose-dependent manner. The low concentrations capable of inhibiting both
      spontaneous (10(-12)M) and LK 1-induced contractions (10(-10) to 10(-9)M) suggest
      that ASTs may be acting as neurohormones/hormones on the hindgut. We have also
      shown that Dippu-AST 7 influences the muscle activity of the Rhodnius dorsal
      vessel at concentrations as low as 10(-11)M.

PMID- 14706535
TI  - Immunolocalization of allatostatin-like neuropeptides and their putative receptor
      in eyestalks of the tiger prawn, Penaeus monodon.
AB  - Allatostatin (AST)-like immunoreactivity (IR) was localized in the eyestalk of
      Penaeus monodon by immunohistochemistry using four anti-AST antibodies. Depending
      on the antisera, AST-like immunoreactivity was detected in neuronal bodies of the
      lamina ganglionalis, cell bodies anterior to the medulla externa and cell bodies
      on the anterior and posterior of the medulla terminalis. Neuronal processes in
      neuropiles of the medulla externa, medulla terminalis, sinus gland and nerve
      fibers in the optic nerve were also recognized. No IR in cell bodies or in nerve
      fibers was found in the medulla interna. Strong AST-like immunoreactivity was
      found in hundreds of cells of the X organ. The localization of AST-like peptides
      suggests that they function as neurotransmitters and/or neuromodulators.
      Antiserum to the Drosophila AST receptor (Dar-2) recognized a single protein in
      P. monodon eyestalk protein extracts that was identical in size to that found in
      Drosophila protein extracts. Using this antiserum the putative P. monodon AST
      receptor was localized to the sinus gland in both juvenile and adult eyestalks.
      To our knowledge this is the first demonstration of a neuropeptide receptor
      localized to the crustacean sinus gland. This suggests that ASTs may function
      directly on the sinus gland as a neuromodulator. In juvenile eyestalks, the
      putative AST receptor was also localized to neuronal X organ cells of the medulla
      terminalis in males but not in females. The significance of this sex-specific
      receptor localization is unclear but emphasizes that ASTs function within the
      nervous system of the eyestalk.

PMID- 14706536
TI  - Diuretic action of the peptide locustatachykinin I: cellular localisation and
      effects on fluid secretion in Malpighian tubules of locusts.
AB  - In insects primary urine is produced by the Malpighian tubules under hormonal
      control. Here we have analysed the effects of the peptide locustatachykinin I
      (Lom-TK-I) on secretion in isolated Malphigian tubules. We also mapped the
      distribution of Lom-TK immunoreactivity in the gut in comparison with Locusta
      diuretic hormone (Lom-DH) and serotonin, two other factors that are active on
      locust tubules. Lom-TK-I produces an immediate, potent and long-lasting
      stimulation of fluid secretion. Furthermore, we show that Lom-TK-I acts
      synergistically with Lom-DH on fluid secretion and demonstrate that Lom-TKs are
      co-localised with Lom-DH in endocrine cells of the midgut ampullae. Thus, the two
      peptides might be released together to act synergistically on fluid secretion.
      Also serotonin and Lom-DH act synergistically and we can demonstrate a plexus of
      serotonin-containing axon processes over the midgut.

PMID- 14706537
TI  - Corazonin promotes tegumentary pigment migration in the crayfish Procambarus
      clarkii.
AB  - The undecapeptide corazonin (pGlu-Thr-Phe-Gln-Tyr-Ser-His-Gly-Trp-Thr-AsnNH(2))
      elicits a retraction of erythrophore pigment granules and dispersion of
      leucophore pigment granules in the crayfish Procambarus clarkii. The effects are
      dose-dependent from 10(-10) to 10(-5)M. Influence on erythrophores is lower than
      that of Red Pigment Concentrating Hormone (RPCH), which is inactive on
      leucophores. Corazonin effects are partly blocked by an anti-corazonin antibody,
      and even less by an anti-RPCH antibody. Corazonin effects are completely
      suppressed by the calcium chelator BAPTA. Immunoreactive somata and fibers were
      identified in various regions of the eyestalk (medulla terminalis, medulla
      interna and medulla externa) with the anti-corazonin antibody. These results
      suggest the possible existence of a corazonin-like peptide in crustaceans.

PMID- 14706538
TI  - Comparative immunohistochemistry and cellular distribution of farnesoic acid O
      methyltransferase in the shrimp and the crayfish.
AB  - Farnesoic acid O-methyltransferase (FAMeT) catalyzes the conversion of farnesoic
      acid (FA) to methylfarnesoate (MF) by the mandibular organ (MO) of crustaceans.
      Here we report the cellular localization of FAMeT and radiochemical assay of
      endogenous FAMeT activity in shrimp (Metapenaeus ensis) and crayfish (Procambarus
      clarkii) tissues. As in the eyestalk (ES), FAMeT is concentrated in specific
      neurosecretory cells of the ventral nerve cord (VNC) whereas only weak FAMeT
      immunoreactivity was observed in the MO. FAMeT was also detected in the ventral
      nerve cord, heart (HET), eyestalk, and muscle of the juvenile shrimp. Although
      the VNC shows the greatest FAMeT immunoreactivity, the heart extract exhibited
      the highest FAMeT enzymatic activity. These results suggest that FAMeT in the VNC
      may be inactive or inactivated at the stages of development tested. Contrary to
      the previous reports in other crustaceans, MO extract in shrimp shows only low
      FAMeT activity. The eyestalk, epidermis, ovary and testis show appreciable FAMeT
      activity. The presence of FAMeT in neurosecretory cells of VNC and eyestalk of
      shrimp and crayfish implies a possible interaction of FAMeT with the eyestalk CHH
      family of neuropeptides. The widespread activity of FAMeT suggests that it has a
      wide spectrum of action in many tissues that contribute to the function and
      regulation of MF synthesis in shrimp and crayfish.

PMID- 14706539
TI  - A nonpeptide provides insight into mechanisms that regulate Drosophila
      melanogaster heart contractions.
AB  - Here we report the effect of a nonpeptide, benzethonium chloride (bztc), on
      Drosophila melanogaster larval, pupal, and adult heart rates in vivo.
      Benzethonium chloride reduced the frequency of spontaneous contractions in the D.
      melanogaster pupal heart, but not in the larval heart or the adult heart as
      measured in noninvasive whole animal preparations. When applied directly to the
      D. melanogaster heart, in the absence of hemolymph, bztc reduced the frequency of
      spontaneous contractions in larval, pupal, and adult hearts. These findings are
      consistent with the conclusion that bztc acts through or is regulated by
      different mechanisms in these three developmental stages. An alternative
      explanation is that larval hemolymph and adult hemolymph contain a material that
      interferes with the effect of the nonpeptide on heart contractions. Bztc mimicked
      the effect of the peptide dromyosuppressin (DMS) on the heart at an equivalent
      concentration; in contrast, 103-fold more nonpeptide is required to mimic the
      effect of DMS on fly gut. These findings are consistent with the presence of
      tissue-specific myosuppressin receptors or mechanisms.

PMID- 14706540
TI  - The synthesis of an analogue of the locust CRF-like diuretic peptide, and the
      biological activities of this and some C-terminal fragments.
AB  - The synthesis is described of an analogue of the locust CRF-like diuretic peptide
      in which methionine in positions 1,3, and 13 is replaced by isosteric methyl
      homoserine residues. This analogue has been tested for biological activity on
      Malpighian tubules in vitro, and feeding behavior in vivo. It is highly active in
      stimulating fluid secretion and accumulation of cAMP in tubules, and on
      increasing the latency to feed and reducing meal duration. A 15 residue fragment
      from the C-terminus of the CRF-like peptide, Locmi-DP(32-46), is fully active in
      the feeding assay, but has only weak ability to stimulate the accumulation of
      cAMP in tubules. Two smaller fragments, Locmi-DP(32-37) and Locmi-DP(41-46), were
      tested but neither had consistent biological activity in any of the assays used
      here. None of the peptides tested have any substantive activity in increasing
      cGMP in tubules.

PMID- 14706541
TI  - A C-terminal aldehyde insect kinin analog enhances inhibition of weight gain and
      induces significant mortality in Helicoverpa zea larvae.
AB  - The first reported examples of C-terminal aldehyde analogs of an insect
      neuropeptide are described. They are hexapeptide insect kinin analogs Boc-VFFPWG
      H and Fmoc-RFFPWG-H. Activity observed for these modified analogs in an in vitro
      insect diuretic assay confirms that the C-terminal aldehyde group is tolerated by
      an insect kinin receptor. The two analogs demonstrate greatly enhanced activity
      over standard C-terminal amide insect kinins in a larval weight gain inhibition
      assay in the corn earworm Helicoverpa zea. Treatment with Boc-VFFPWG-H led to
      significant increases in larval mortality at doses of 500pm (45%) and 5nm (67%).
      Boc-VFFPWG-H represents a lead analog in the development of novel,
      environmentally friendly pest insect management agents based on the insect kinin
      class of neuropeptides.

PMID- 14706542
TI  - Insect allatotropins belong to a family of structurally-related myoactive
      peptides present in several invertebrate phyla.
AB  - Originally named for its ability to stimulate juvenile hormone production by
      lepidopteran corpora allata, allatotropin has emerged as a neuropeptide with
      multiple neural, endocrine and myoactive roles. This paper describes the
      experimental evidence for allatotropin action, its localization in several
      species of insects, and its multiple effects on a variety of different tissues
      that lead to increased hemolymph circulation and gut motility. The overall
      physiological effects may also include species-specific effects such as the
      regulation of nutrient absorption, modulation of the circadian cycle and
      migratory preparedness. In addition, we present evidence suggesting that
      allatotropins are members of a family of myoactive peptides found in several
      invertebrate phyla. Finally, we speculate that the myoactive properties of
      allatotropins are basal and it is likely that the stimulatory action of
      allatotropins on juvenile hormone synthesis evolved secondarily.

PMID- 14706543
TI  - Genomics, evolution and biological functions of the pacifastin peptide family: a
      conserved serine protease inhibitor family in arthropods.
AB  - The last decade, a new serine protease inhibitor family has been described in
      arthropods. Eight members were purified from the locusts Locusta migratoria (LMPI
      1-2 and HI) and Schistocerca gregaria (SGPI-1-5). The light chain of the
      heterodimeric protease inhibitor pacifastin, from the freshwater crayfish
      Pacifastacus leniusculus, was found to be composed of nine consecutive inhibitory
      domains (PLDs). These domains share a pattern of six conserved cysteine residues
      (Cys-Xaa(9-12)-Cys-Asn-Xaa-Cys-Xaa-Cys-Xaa(2-3)-Gly-Xaa(3-6)-Cys-Thr-Xaa(3)-Cys)
      with the locust inhibitors. Via cDNA cloning, eight pacifastin-related precursors
      have been identified in locusts. Interestingly, additional pacifastin-related
      precursors have been identified in Diptera, Lepidoptera and Coleoptera utilising
      an in silico data mining approach.

PMID- 14706544
TI  - Determination of the HIV-1 gp41 fusogenic core conformation modeled by synthetic
      peptides: applicable for identification of HIV-1 fusion inhibitors.
AB  - Triggered by receptor binding of gp120, the human immunodeficiency virus type 1
      (HIV-1) gp41 changes its conformation to a fusogenic six-helix bundle structure.
      In the present study, this core conformation modeled by the peptides derived from
      the gp41 N- and C-terminal heptad repeat regions was determined by fluorescence
      native polyacrylamide gel electrophoresis and size exclusion high-performance
      liquid chromatography (HPLC). Two previously described small molecule HIV-1
      fusion inhibitors significantly blocked the six-helix bundle formation. It
      suggests that these biophysical techniques can be used in a novel way to study
      the conformational change of gp41 during virus entry into cells and to identify
      HIV-1 fusion inhibitors.

PMID- 14706545
TI  - Comparative activities of cecropin A, melittin, and cecropin A-melittin peptide
      CA(1-7)M(2-9)NH2 against multidrug-resistant nosocomial isolates of Acinetobacter
      baumannii.
AB  - The in vitro activity of three polycationic peptides, cecropin A, melittin, and
      cecropin A-melittin hybrid peptide CA(1-7)M(2-9)NH2, alone and in combination
      with various clinically used antimicrobial agents, was investigated against 32
      nosocomial isolates of Acinetobacter baumannii. Antimicrobial activities were
      measured by MIC, MBC and bacterial killing assay. The peptides demonstrated
      different ranges of inhibitory values: overall, the organisms were more
      susceptible to CA(1-7)M(2-9)NH2 (MIC range, 0.25-16 mg/l) than to cecropin A
      (0.50-32 mg/l) and melittin (0.50-32 mg/l). Synergy was observed when CA(1-7)M(2
      9)NH2 and melittin were combined with beta-lactam antibiotics.

PMID- 14706546
TI  - Structural characterization and expression analysis of prothoracicotropic hormone
      in the corn earworm, Helicoverpa zea.
AB  - The cDNA encoding prothoracicotropic hormone (PTTH), the brain neuropeptide that
      stimulates the prothoracic glands to synthesize ecdysone, was cloned from the
      corn earworm Helicoverpa zea (Hez). The amino acid sequence deduced from the cDNA
      indicates a molecular structure that is distinct from the PTTH's reported in
      other Lepidoptera, but all contain an identical proteolytic cleavage site and the
      seven cysteine residues that are essential for activity. Northern hybridization
      shows a single mRNA present in the brain-subesophageal ganglion complex. Using RT
      PCR, we observed constant amounts of PTTH mRNA during larval development but
      large fluctuations at pupation and prior to adult eclosion.

PMID- 14706547
TI  - Insect diapause-specific peptide from the leaf beetle has consensus with a
      putative iridovirus peptide.
AB  - Diapause and hibernation during periods of environmental adversity are essential
      features of the life cycle in many organisms, yet the molecular basis for these
      events differs among animals. We have identified an endogenous
      diapause/hibernation-specific peptide, from the leaf beetle Gastrophysa
      atrocyanea. This peptide provides antifungal activity, acts as a N-type voltage
      gated Ca2+ channel blocker, and has a new consensus sequence with an unknown
      polypeptide encoded in the insect iridescent virus. These results indicate that
      the diapause-specific peptide may be utilized as a probe to analyze and compare
      functional and evolutional aspects of the life cycles of insects and
      iridoviruses.

PMID- 14706548
TI  - Histochemical localization of the PBAN receptor in the pheromone gland of
      Heliothis peltigera.
AB  - The presence of the pyrokinin (PK)/ Pheromone biosynthesis activating
      neuropeptide (PBAN) receptor in pheromone gland cells of Heliothis peltigera
      females was demonstrated, and its spatial distribution in the ovipositor was
      visualized with two photo-affinity biotinilated ligands: BpaPBAN1-33NH(2) and
      BpaArg(27)-PBAN28-33NH(2). Light microscopy histological studies revealed that
      the gland is contained within the inter-segmental membrane (ISM) between the 8th
      and 9th abdominal segments. The gland was found to be composed of a single layer
      of columnar epithelial cells positioned under the inter-segmental cuticle.
      Similar epithelial cells were also found in the dorsal and ventral regions of the
      9th abdominal segment. All regions containing the glandular cells bound both
      ligands, indicating presence of the PK/PBAN receptor. The patterns obtained with
      both ligands were similar, hinting at the possibility that either both ligands
      bind to the same receptor, or, that if there are two distinct receptors, their
      spatial distribution throughout the gland is very similar.

PMID- 14706549
TI  - A cyclo peptide activates signaling events and promotes growth and the production
      of the bone matrix.
AB  - The interaction of bone cells and their underlying extracellular matrix impacts
      biological processes such as maintenance of tissue integrity. The biological
      recognition of the extracellular matrix by attached cells is mediated by the
      activity of integrins that recognize adhesive-specific domains. The most widely
      recognized adhesive motif is the RGD sequence, common to many of the adhesive
      matrix molecules. Here, we show that cyclo DFKRG which was previously selected to
      increase cell adhesion of human bone marrow stromal cells (HBMSC), increases both
      cell differentiation and mineralization through activation of tyrosine kinases,
      focal adhesion kinase (p(125)FAK) and Mitogen Activated Protein (MAP) kinases.

PMID- 14706550
TI  - Analysis of conserved residues of the human puromycin-sensitive aminopeptidase.
AB  - The puromycin-sensitive aminopeptidase (ApPS) is a zinc metallopeptidase involved
      in the degradation of neuropeptides. Putative catalytic residues of the enzyme,
      Cys146, Glu338, and Lys396 were mutated, and the resultant mutant enzymes
      characterized. ApPS C146S exhibited normal catalytic activity, ApPS E338A
      exhibited decreased substrate binding, and ApPS K396I exhibited decreases in both
      substrate binding and catalysis. ApPS K396I and ApPS Y394F were analyzed with
      respect to transition state inhibitor binding. No effect was seen with the K396I
      mutation, but ApPS Y394F exhibited a 3.3-fold lower affinity for RB-3014, a
      transition state inhibitor, indicating that Tyr394 is involved in transition
      state stabilization.

PMID- 14706551
TI  - Aminopeptidases in visceral organs during alterations in body fluid volume and
      osmolality.
AB  - Enzymatic cleavage of some peptides in the local environment could be included
      among the mechanisms related to the regulation of hydrosaline balance. In order
      to examine this hypothesis, we measured representative aminopeptidase activities
      in visceral organs of rats after applying certain hydrosaline challenges.
      Decreased levels (about 30%) of particulate puromycin-insensitive-neutral
      aminopeptidase in the renal medulla and of soluble acid aminopeptidase in the
      lung were observed under hyperosmolality and hypovolemia. Decreased levels (more
      than 45%) of particulate type-I-pyroglutamyl aminopeptidase in the heart were
      observed under altered volemia. These results indicate that aminopeptidases at
      these anatomical locations might be involved in the regulation of body fluid
      volume and osmolality.

PMID- 14706552
TI  - Human galanin expresses amphipathic properties that modulate its vasoreactivity
      in vivo.
AB  - The purpose of this study was to determine whether human galanin, a pleiotropic
      30-amino acid neuropeptide, expresses amphipathic properties in vitro and, if so,
      whether these properties modulate its vasoactive effects in the intact peripheral
      microcirculation. We found that human galanin aggregates in an aqueous solution
      and forms micelles with a critical micellar concentration (CMC) of 0.4 microM. In
      addition, the peptide interacted with model membrane as indicated by long and
      significant increase of the surface pressure of the biomimetic monolayer membrane
      in vitro. Interactions of human galanin with sterically stabilized phospholipid
      micelles (SMM) were not associated with a significant change in peptide
      conformation. Using intravital microscopy, we found that suffusion of human
      galanin alone elicited significant concentration-dependent vasoconstriction in
      the intact hamster cheek pouch. This response was amplified when human galanin in
      SSM was suffused onto the cheek pouch. The effects of human galanin alone and in
      SSM were mediated by galanin receptors because galantide, a galanin receptor
      antagonist, abrogated galanin-induced vasoconstriction. Collectively, these data
      show that human galanin expresses amphipathic properties in the presence of
      phospholipids which in turn amplifies its vasoactive effects in the intact
      peripheral microcirculation.

PMID- 14706553
TI  - Octreotide: a new approach to the management of acute abdominal hypertension.
AB  - Acutely increased intra-abdominal pressure (IAP) may lead to abdominal
      compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an
      important role. The main goal of the management of ACS is to lower the intra
      abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic
      somatostatin analogue, lowers the splanchnic perfusion. The aim of this study was
      to investigate whether OCT improves the reperfusion injury after decompression of
      acute abdominal hypertension.Under anesthesia, a catheter was inserted
      intraperitoneally and using an aneroid manometer connected to the catheter, IAP
      was kept at 20 mmHg (ischemia group; I) for 1h. In the I/R group, pressure
      applied for an hour was decompressed and 1h reperfusion period was allowed. In
      another group of I/R, OCT was administered (50 microg/kg i.p.) immediately before
      the decompression of IAP. The results demonstrate that kidney and lung tissues of
      malondialdehyde (MDA; an end product of lipid peroxidation) levels and
      myeloperoxidase (MPO; index of tissue neutrophil infiltration) activity were
      elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in
      I/R group (P<0.001). Moreover, OCT treatment applied in the I/R group reduced the
      elevations in blood urea nitrogen (BUN) and serum creatinine levels. Our results
      implicate that IAP causes oxidative organ damage and OCT, by reducing splanchnic
      perfusion and controlling the reperfusion of abdominal organs, could improve the
      reperfusion-induced oxidative damage. Therefore, its therapeutic role as a
      "reperfusion injury-limiting" agent must be further elucidated in IAP-induced
      abdominal organ injury.

PMID- 14706554
TI  - Sequence, distribution and quantification of the motilin precursor in the cat.
AB  - Due to motilin's relation to the migrating motor complex (MMC), the physiology of
      motilin has been mostly studied in man and dog. The cat does not have an MMC
      pattern, and little is known about cat motilin. Therefore we identified the cat
      motilin precursor (GenBank accession no. AF127917) and developed a quantitative
      polymerase chain reaction (PCR) to explore its distribution in the
      gastrointestinal tract and in the central nervous system (CNS). The precursor is
      closely related to the dog precursor and consists of an open reading frame of
      348bp encoding the signal peptide (25 amino acids), the motilin sequence (22
      amino acids) and the motilin associated peptide (69 amino acids). One amino acid
      of the signal peptide was subject to gene polymorphism. Quantification of motilin
      messenger RNA (mRNA) was for the first time achieved. It is most abundant in the
      gastrointestinal tract, with the highest concentration in the duodenum, the
      lowest in the colon and is not detectable in the corpus. However an important
      expression was also observed in several regions of the CNS, except the striatum
      and cerebral cortex. The highest level was in the hypothalamus (although 23-fold
      lower than in the duodenum), the lowest level in the pons. Moderate levels were
      found in the thyroid. These data suggest that the physiological role of motilin
      may extend beyond its effect on gastrointestinal motility.

PMID- 14706556
TI  - Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B
      subunits mRNA expression in rat hippocampus after MCH administration.
AB  - The present study attempts to determine which mechanisms underlie the retrograde
      facilitation of memory induced by microinjection hippocampal melanin
      concentrating hormone (MCH) on the inhibitory avoidance paradigm. Previous
      reports using this test on the hippocampus suggest that NMDA receptor-mediated
      mechanisms are involved in memory processing and are also necessary for the
      induction of long-term potentiation (LTP) of the hippocampal dentate gyrus. In
      addition, alterations in expression of synaptic NMDA subunits in the hippocampus
      have been associated with memory formation of an inhibitory avoidance task. We
      have studied the effects of the neuropeptide upon the electrophysiological
      parameters using hippocampal slices from rats injected with the peptide and
      tested in step-down tests as well as possible changes in the mRNA expression of
      NMDA receptor subunits. We postulate that the increased facility to induce LTP,
      and the overexpression of this N-methyl-D-aspartate mRNA receptor subunits
      induced by MCH, could be behind the retrograde facilitation observed after MCH
      hippocampal microinjection.

PMID- 14706555
TI  - Effects of PKA modulation on the expression of neuropeptide Y in rat amygdaloid
      structures during ethanol withdrawal.
AB  - We recently reported that neuropeptide Y (NPY) protein levels and cAMP responsive
      element binding (CREB) protein phosphorylation are lower in amygdaloid structures
      during ethanol withdrawal after chronic exposure. Furthermore, we reported that
      normalization of CREB phosphorylation by infusing protein kinase A (PKA)
      activator into the central amygdala prevents anxiety-like effects in rats during
      ethanol withdrawal. Here we investigated whether normalization of CREB
      phosphorylation by infusing PKA activator (Sp-cAMP) into the central amygdala
      also normalizes the expression of NPY during ethanol withdrawal. Sprague-Dawley
      male rats were cannulated targeting the central amygdala and then treated either
      with Lieber-DeCarli ethanol diet or control diet for 15 days. Subsequently
      ethanol-fed rats were withdrawn for 0 and 24h. The control-diet fed and ethanol
      withdrawn rats were infused twice with PKA activator or inhibitor (Rp-cAMP). The
      protein and mRNA levels of NPY were determined in amygdaloid structures using
      gold-immunolabeling and the in situ RT-PCR procedure. It was found that chronic
      ethanol treatment has no effect on mRNA and protein levels of NPY in the central,
      medial, or basolateral amygdala. On the other hand, ethanol withdrawal produced
      significant reductions in mRNA and protein levels of NPY in the central and
      medial but not in the basolateral amygdala. The reductions in mRNA and protein
      levels of NPY were normalized in the central amygdala by infusion with PKA
      activator in ethanol-withdrawn rats. On the other hand, PKA-inhibitor infusion
      does not have any effect on mRNA and protein levels of NPY in the central
      amygdala of ethanol-withdrawn rats, but significantly decreased the expression of
      NPY in the central amygdala of control-diet fed rats. These results suggest that
      the decreased cellular expression of NPY in the central amygdala may play an
      important role in the CREB-mediated regulation of anxiety-like behaviors during
      ethanol withdrawal.

PMID- 14706557
TI  - The neuroprotective peptide NAP inhibits the aggregation of the beta-amyloid
      peptide.
AB  - Alzheimer's disease (AD) is characterized by brain plaques containing the beta
      amyloid peptide (Abeta). One approach for treating AD is by blocking Abeta
      aggregation. Activity-dependent neuroprotective protein contains a peptide, NAP
      that protects neurons in culture against Abeta toxicity. Here, NAP was shown to
      inhibit Abeta aggregation using: (1) fluorimetry; (2) electron microscopy; (3)
      high-throughput screening of Abeta deposition onto a synthetic template
      (synthaloid); and (4) Congo Red staining of neurons. Further assays showed biotin
      NAP binding to Abeta. These results suggest that part of the neuroprotective
      mechanism exerted by NAP is through modulation of toxic protein folding in the
      extracellular milieu.

PMID- 14706558
TI  - Synthesis and biological evaluation of oxytocin analogues containing L-alpha-t
      butylglycine [Gly(Bu t)] in positions 8 or 9.
AB  - We report the solid phase synthesis and some pharmacological properties of
      seventeen new oxytocin (OT) analogues. Basic modification at positions 8 and/or 9
      (introduction of L-alpha-t-butylglycine [Gly(Bu(t))]) was combined with D-Cys(6),
      D-Tyr(Et)(2), Mpa(1) or Pen(1) modifications and their various combinations. We
      also present properties of two previously reported re-synthesized analogues
      ([Gly(Bu(t))(8)]OT and [Mpa(1), Gly(Bu(t))(8)]OT). The analogues were tested for
      rat uterotonic activity in vitro, in the rat pressor assay and for binding
      affinity to human OTR.

PMID- 14706559
TI  - Synthesis and binding characteristics of a novel enkephalin analogue, [3H]Tyr-D
      Ala-Gly-Phe-D-Nle-Arg-Phe.
AB  - The endogenous opioid heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MERF) has been
      shown to interact with multiple opioid as well as non-opioid sites in mammalian
      brain membranes. To increase the stability and bioavailability of MERF, new
      synthetic derivatives with D-amino acid substitutions were prepared and studied.
      One of the new compounds in this series, Tyr-D-Ala-Gly-Phe-D-Nle-Arg-Phe (DADN),
      had only moderate affinity in competing with [3H]MERF, whereas it displayed the
      highest potency in producing antinociception following intrathecal
      administration. DADN was radiolabeled with 41Ci/mmol specific activity. Specific
      binding of [3H]DADN was saturable, stereoselective and of high affinity. Chemical
      stability, increased micro-receptor selectivity, and hydrophobicity of the
      peptide all contribute to the effectiveness observed in biochemical and
      pharmacological studies.

PMID- 14706560
TI  - Leptin fails to reduce ethanol intake in Marchigian Sardinian alcohol-preferring
      rats.
AB  - Leptin, a hormone secreted by the adipocytes and involved in feeding and energy
      balance control, has been proposed to modulate alcohol craving in mice and
      humans. This study evaluated whether leptin modulates alcohol intake in
      Marchigian Sardinian alcohol-preferring (msP) rats. Rats were offered 10% ethanol
      either 2h per day at the beginning of dark period of the 12:12h light/dark cycle,
      or 24h per day. Leptin was injected into the lateral ventricle (LV), the third
      ventricle (3V), or intraperitoneally (IP) once a day, 1h before the onset of the
      dark period. Neither acute nor chronic (9 days) leptin injections (1 or 8microg
      per rat) into the LV or 3V modified ethanol intake in male msP rats, offered
      ethanol 2h per day. Chronic LV injection of leptin (8 or 32 microg per rat in
      male rats and 8 or 16 microg per rat in female rats for 7 days), or chronic IP
      injections of leptin (1mg/kg in male rats for 5 days) failed to modify the intake
      of ethanol, offered 24h per day. Finally, chronic LV leptin injections (8 or 32
      microg per rat for 12 days) did not modify ethanol intake in male msP rats,
      adapted to ad libitum access to ethanol and then tested after a 6-day period of
      ethanol deprivation. In contrast, in most of these conditions leptin
      significantly reduced food intake. These data do not support a role for leptin in
      alcohol intake, preference, or craving in msP rats.

PMID- 14706561
TI  - Tachykinins in the normal and gonadotropin-stimulated ovary of the mouse.
AB  - In this investigation, substance P (SP) and neurokinin A (NKA) concentrations
      have been determined in the ovary of control prepubertal mice, and prepubertal
      mice injected with pregnant mare serum (PMS) gonadotropin, an equine gonadotropin
      with predominant FSH action, or with PMS followed by human chorionic gonadotropin
      (hCG), which produces heavily luteinized ovaries after the stimulation with PMS.
      Control animals were injected with saline. The ovaries of animals treated with
      gonadotropins were heavier than the control ovaries, the combination of PMS plus
      hCG produced significantly heavier ovaries than PMS alone. The concentrations of
      SP and NKA in the ovaries of the animals treated with PMS or PMS/hCG were
      significantly lower than in control ovaries. No significant differences in
      ovarian tachykinin concentrations were observed between PMS and PMS/hCG-treated
      animals. The total ovarian content of SP was lower in PMS-injected animals as
      compared with the controls. The total ovarian content of NKA was not
      significantly different in the three groups of animals studied. These results
      show that ovaries stimulated with gonadotropins have lower concentrations of
      tachykinins than normal ovaries at the same age. It is therefore evident that
      gonadotropins can affect tachykinin stores in the ovaries of mice.

PMID- 14706562
TI  - The PAR-1-activating peptide facilitates pepsinogen secretion in rats.
AB  - Protease-activated receptor-2 (PAR-2) is abundantly expressed in gastric mucosal
      chief cells, facilitating pepsinogen secretion. In the present study, we
      investigated whether PAR-1, a thrombin receptor, could modulate pepsinogen
      secretion in rats. The PAR-1-activating peptide TFLLR-NH(2) as well as the PAR-2
      activating peptide SLIGRL-NH(2), administered i.v. repeatedly at 1-h intervals,
      significantly increased gastric pepsinogen secretion over 2-4 h (after two to
      four doses). In contrast, the control peptide FTLLR-NH(2), given in the same
      manner, had no such effect. Thus, PAR-1, like PAR-2, might function to facilitate
      pepsinogen secretion, suggesting a novel role of the thrombin-PAR-1-pathway in
      the stomach.

PMID- 14706563
TI  - Synergistic interactions between cannabinoid and opioid analgesics.
AB  - Cannabinoids and opioids both produce analgesia through a G-protein-coupled
      mechanism that blocks the release of pain-propagating neurotransmitters in the
      brain and spinal cord. However, high doses of these drugs, which may be required
      to treat chronic, severe pain, are accompanied by undesirable side effects. Thus,
      a search for a better analgesic strategy led to the discovery that delta 9
      tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana,
      enhances the potency of opioids such as morphine in animal models. In addition,
      studies have determined that the analgesic effect of THC is, at least in part,
      mediated through delta and kappa opioid receptors, indicating an intimate
      connection between cannabinoid and opioid signaling pathways in the modulation of
      pain perception. A host of behavioral and molecular experiments have been
      performed to elucidate the role of opioid receptors in cannabinoid-induced
      analgesia, and some of these findings are presented below. The aim of such
      studies is to develop a novel analgesic regimen using low dose combinations of
      cannabinoids and opioids to effectively treat acute and chronic pain, especially
      pain that may be resistant to opioids alone.

PMID- 14706564
TI  - Estrogenic activities of Ginkgo biloba extracts.
AB  - Ginkgo biloba extracts (GBE) are extracted from the leaves of Ginkgo biloba tree.
      GBE contains 24% of phytoestrogens, which is kaempferol, quercetin, and
      isorhamnetin. It has been reported that phytoestrogens could be a part of SERMs
      (Selective estrogen receptor modulators) and possibly the alternative HRT
      (Hormone replacement therapy) for postmenopausal women. The goal of this study
      was to investigate the potencies of GBE and its major components (quercetin,
      kaempferol, isorhamnetin) for estrogenic effect, which confirms the capacity as
      an alternative HRP. It was found that GBE and its major components exerted a dual
      action on ER-alpha and ER-beta in competitive binding assay. The binding affinity
      of these chemicals to ER-beta was higher than to ER-alpha. In the E-screen assay,
      these chemicals induced cell proliferation in ER-positive MCF-7 cell, but not in
      ER-negative MDA-MB-231 cells. The cell proliferation induced by these chemicals
      was blocked by tamoxifen. Also, GBE and its major components induced pS2 and PR
      (progesterone receptor) transcription in MCF-7 cells. Therefore these results
      indicated that GBE and its major components had the weak estrogenic activities
      through the estrogen response pathway by an interaction with the ER. In
      conclusion, we provided the evidence of potential estrogenic activities of GBE,
      which could be useful as an alternative HRP. However, further studies are
      required to assess the physiological significance of GBE in animals and humans.

PMID- 14706565
TI  - Evidence for an intracellular site of action in the heart for two hydrophobic
      cardiac steroids.
AB  - Although cardiac steroids (CS) have long been used to treat cardiac
      insufficiency, the mechanism(s) of action of these agents remain open to
      question. While many results indicate that inhibition of Na+,K+-ATPase underlies
      both the therapeutic and toxic actions of CS, other studies suggest that actions
      on the SR membrane system may be important. We used two experimental approaches
      and measurements of left ventricular diastolic pressure (LVDP) in isolated guinea
      pig hearts to test whether CS had an intracellular site of action. In the first
      approach, we compared the inotropic effects of a hydrophilic CS, ouabain, and a
      hydrophobic CS, digitoxin, after the activity of the Na+ pump was reduced by
      perfusing hearts with solutions maintained at 5 degrees C. Under these
      conditions, exposure of hearts to 1 microM ouabain for 60 min did not increase
      LVDP above control levels. In contrast, an equi-effective concentration of
      digitoxin (0.3 microM) increased LVDP by 40 +/- 8.5% (p < 0.01) over pre-drug
      control levels. In the second experimental approach, we compared the inotropic
      effects of ouabain and digitoxin in the presence of rapid-cooling contractures
      (RCC), which result in the release of SR Ca2+. Hearts were perfused with Tyrode
      solution or Tyrode solution containing either digitoxin (0.3 microM) or ouabain
      (1 microM) for 180 sec, rapidly cooled and the RCC responses were analyzed.
      Compared to RCC elicited in Tyrode solution alone, or in Tyrode solution
      containing ouabain, RCC in the presence of digitoxin reached peak amplitudes more
      rapidly, but elicited reduced peak amplitude values. Based on these findings, we
      suggest that: 1) the ability of the hydrophobic CS, digitoxin, but not the
      hydrophilic CS, ouabain, to produce a positive inotropic effect at 5 degrees C,
      when the activity of the Na+ pump is markedly reduced, is consistent with a
      mechanism other than Na+ pump inhibition and involves an intracellular location;
      and 2) the diminished RCC observed in the presence of the hydrophobic CS,
      digitoxin, indicate that this alternative mechanism may involve effects on the SR
      Ca2+ release channel.

PMID- 14706566
TI  - VIP receptor antagonists inhibit mammary carcinogenesis in C3(1)SV40T antigen
      mice.
AB  - The effects of a vasoactive intestinal peptide (VIP) receptor antagonist on
      mammary carcinogenesis were investigated using the C3(1)SV40T antigen (ag) mice.
      Ten microg/day VIPhybrid (VIPhyb) administered daily subcutaneously increased
      significantly the survival of C3(1)SV40Tag mice. At 5.2 months, VIPhyb
      significantly reduced the mammary tumor burden in C3(1)SV40Tag mice relative to
      control animals. 125I-VIP bound with high affinity to mouse mammary tumor
      homogenate. Because (Lys15, Arg16, Leu27)VIP1-7GRF8-27 (VPAC1 selective) but not
      Ro25-1553 (VPAC2 selective) inhibited specific 125I-VIP binding to mammary tumor
      membranes with high affinity, VPAC1 receptors predominate. By RT-PCR, VPAC1
      receptor mRNA was detected in mammary tumors. By Western blot, a major 60 Kdalton
      band was detected in mammary tumor extracts using VPAC1 receptor antisera. By
      immunocytochemistry, VPAC1-R immunostaining was detected in the cytosol and
      plasma membrane but not the nucleus of fixed mammary tumor tissue. Using laser
      capture microdissected tumor cells and surface enhanced laser
      desorption/ionization (SELDI) techniques on mammary tumor cells, the proteomic
      profile was altered in mice treated with VIPhyb. Because VPAC1 receptor
      antagonists increase the survival and reduce the tumor burden in C3(1)SV40Tag
      mice, they may function as chemopreventive agents in mammary cancer.

PMID- 14706567
TI  - Chronic somatostatin treatment affects pituitary gonadotrophs, ovaries and onset
      of puberty in rats.
AB  - The effects of chronic somatostatin (SRIH-14) treatment on the pituitary
      gonadotrophs (FSH and LH cells) and ovaries of female Wistar rats were examined.
      Females were given 20 microg/100 g b.w. twice per day from the immature (23rd
      day) till the adult period of life (71st day). The onset of puberty was
      determined by daily examination for vaginal opening. The peroxidase
      antiperoxidase immunocytochemical procedure was used to study the gonadotrophs.
      Changes in the number per unit area (mm2), cell volume and volume densities of LH
      and FSH-immunoreactive cells were evaluated by morphometry and stereology.
      Ovaries were analysed by simple point counting of follicles and corpora lutea
      (CL). Follicles were divided by size according to the classification of Gaytan
      and Osman. The mitotic indexes of granulosa and theca cells in the follicles were
      estimated at all stages of folliculogenesis. The number, volume and the volume
      density of FSH- and LH-immunoreactive cells decreased after chronic SRIH-14
      treatment, particularly the latter. In the ovary, SRIH-14 treatment decreased the
      number of healthy follicles at all phases of folliculogenesis, lowered the
      mitotic indexes of granulosa and theca cells but increased the number of atretic
      follicles. Healthy CL were fewer in number, while regressive CL were increased.
      Vaginal opening occurred at a later age in treated females. It can be concluded
      that chronic SRIH-14 treatment markedly inhibited LH cells and to a lesser extent
      FSH cells. In the ovary SRIH-14 inhibited folliculogenesis, enhanced atretic
      processes and lowered proliferative activity of granulosa and theca cells. It
      also delayed puberty onset.

PMID- 14706568
TI  - Kidney adaptation in nitric oxide-deficient Wistar and spontaneously hypertensive
      rats.
AB  - We investigated the renal structural and functional consequences of nitric oxide
      (NO) deficiency co-treated with angiotensin-converting enzyme inhibitor (ACEi) in
      20 adult male Wistar rats and 20 spontaneously hypertensive rats (SHR). The
      animals were separated into eight groups (n = 5) and treated for 30 days:
      Control, L-NAME (NO deficient group), Enalapril, L-NAME + Enalapril. The elevated
      blood pressure in NO deficient rats was partially reduced by enalapril. Serum
      creatinine was elevated in L-NAME-SHRs and effectively treated with enalapril.
      The proteinuria was significantly higher only in L-NAME-SHRs, and this was
      reduced by treatment with ACEi. The glomerular volume density (Vv(gl)) in L-NAME
      rats, both Wistar and SHR, was greater than in matched control rats, and
      enalapril treatment effectively prevented this Vv(gl) increase. No significant
      differences were observed in tubular volume density, Vv(tub), or tubular surface
      density, Sv(tub), in all Wistar groups. The Vv(tub) was smaller in L-NAME-SHRs
      than in control SHRs, and this tubular alteration was not prevented by enalapril.
      The Sv(tub) was not different among the SHR groups. In Wistar rats no changes
      were seen in vascular surface density, but a greatly increased cortical vascular
      volume density was seen in the enalapril treated rats. The vascular length
      density was greatly diminished in NO deficient rats that was effectively
      prevented with enalapril treatment. The vascular cortical renal stereological
      indices are normally reduced in SHRs. Administration of enalapril, but not L
      NAME, changed this tendency. However, enalapril was not totally effective in
      preventing vascular damage in SHR NO deficient animals.

PMID- 14706569
TI  - Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine
      receptor ligands.
AB  - Mouse paw oedema induced by carrageenan is used to determine if glucocorticoids
      are involved in the anti-inflammatory effects of peripheral benzodiazepine
      receptor ligands. The anti-inflammatory responses elicited by i.p. treatment with
      1-(2-chlorophenyl)-N-methyl-N (1-methyl-propyl)-3-isoquinoline carboxamide
      (PK11195) and 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1, 4
      benzodiazepin-2 (Ro5-4864) were reversed by aminoglutethimide, an inhibitor of
      steroidal synthesis. Intraplantar injection into the ipsilateral paw of Ro5-4864,
      but not PK11195, inhibited the formation of paw oedema and this effect was
      reversed by aminoglutethimide. These results suggest that glucocorticoids are
      involved in the systemic and local anti-inflammatory effects of Ro5-4864 and only
      in the systemic response to PK11195.

PMID- 14706570
TI  - Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus
      gastroenteritis induced convulsion.
AB  - Nitric oxide (NO) is a highly reactive free radical that is involved in a variety
      of different biological process. In recent reports, the putative role of NO in
      the neuropathogenesis of brain inflammation has been demonstrated. And then the
      relation between neuronal NO and convulsive seizures induced by virus has been
      suggested. However, there are few reports about NO in vivo under viral
      neurological infections. In order to evaluate the relation between NO production
      and neurological disorders induced by viral infection, sixty-six cases including
      11 patients with rotavirus gastroenteritis admitted for convulsions were examined
      in this study. NO metabolites (NOx) levels in both serum and cerebrospinal fluid
      obtained from rotavirus gastroenteritis patients with convulsion were much higher
      than in those of patients with purulent meningitis, encephalitis, febrile
      convulsion or in the control group. There was a relative correlation between IL-6
      and NOx in some cases. These results indicated that NO may have a
      pathophysiological role in convulsions associated by rotavirus infection either
      through indirect or direct effects of NO. Consequently, NOx inhibitors might be
      helpful for the treatment of rotavirus encephalopathy.

PMID- 14706571
TI  - Investigation of the role of epigenetic modification of the rat glucokinase gene
      in fetal programming.
AB  - Fetal malnutrition is associated with development of impaired glucose tolerance,
      diabetes and hypertension in later life in humans and several mammalian species.
      The mechanisms that underlie this phenomenon of fetal programming are unknown. We
      hypothesize that adverse effects in utero and early life may influence the basal
      expression levels of certain genes such that they are re-set with long-term
      consequences for the organism. An excellent candidate mechanism for this re
      setting process is DNA methylation, since post-natal methylation patterns are
      largely established in utero. We have sought to test this hypothesis by
      investigating the glucokinase gene (Gck) in rat offspring programmed using a
      maternal low protein diet model (MLP). Northern blot reveals that fasting levels
      of Gck expression are reduced after programming, although this distinction
      disappears after feeding. Bisulphite sequencing of the hepatic Gck promoter
      indicates a complete absence of methylation at the 12 CpG sites studied in
      controls and MLP animals. Non-expressing cardiac tissue also showed no DNA
      methylation in this region, whereas brain and all fetal tissues were fully
      methylated. These findings are not consistent with the hypothesis that
      programming results from differential methylation of Gck. However, it remains
      possible that programming may influence methylation patterns in Gck at a distance
      from the promoter, or in genes encoding factors that regulate basal Gck
      expression.

PMID- 14706572
TI  - Estrogenic activity of an antioxidant, nordihydroguaiaretic acid (NDGA).
AB  - Nordihydroguaiaretic acid (NDGA), an antioxidant which has been used to preserve
      oils and foods, has recently become well known as a putative anticancer agent.
      Although NDGA is a member of the lignan family, its hormonal activities have not
      been well investigated. Here we show that NDGA has in vitro estrogenic activity
      in the ERE-luc reporter system using NIH3T3 cells, and in the estrogen-responsive
      cell growth assay in a pituitary cell line, MtT/E-2. Uterotropic assay in rats
      indicated that NDGA has estrogenic activity in vivo as well, albeit weak.
      Interestingly it preferentially induced ERalpha mediated ERE-luc activity,
      although it showed similar binding affinity to both ERalpha and ERbeta. With
      ERbeta, on the other hand, NDGA showed only weak agonistic action, and
      antagonized the estrogenic action of 17beta-estradiol when the two were
      coadministered. These data suggest that NDGA is an estrogenic agonist for ERalpha
      : ERE transcription and a mixed agonist/antagonist for ERbeta mediated ERE
      transactivation.

PMID- 14706573
TI  - Mechanism of (-)clausenamide induced calcium transient in primary culture of rat
      cortical neurons.
AB  - (-)clausenamide is a compound isolated from Clausena lansium (lour) Skeel with
      nootropic effects. At the present study, we investigated the clausenamide induced
      Ca2+ signaling in primary cultures of rat cortical neurons by using laser
      confocal microscopy. The mean amplitude of (-)clausenamide (1 microM) induced
      Ca2+ transient was similar in extracellular solution with or without calcium; and
      (-)clausenamide failed to trigger calcium transient after treatment with
      endoplasmic reticulum Ca2+ pumps inhibitor BHQ to exhaust intracellular Ca2+
      stores. This result suggested that the primary source of (-)clausenamide induced
      Ca2+ transient was from internal stores. Application of IP3 receptor inhibitor
      MgCl2 and PLC-gamma inhibitor U73122 suppressed (-)clausenamide induced Ca2+
      transient, suggesting that the major source of (-)clausenamide induced Ca2+
      transient was from IP3 receptor pathway. We also found that mitochondria were
      involved in (-)clausenamide triggered Ca2+ transient. The distinctive spatial and
      temporal characteristic of (-)clausenamide induced Ca2+ transient may play an
      important role in its action.

PMID- 14706574
TI  - Localization of the 31-amino-acid endothelin-1 in hamster tissue.
AB  - Endothelin (ET)-1(1-31) is a novel vasoconstrictor peptide produced by human mast
      cell chymase, which selectively cleaves big ET-1 at the Try(31)-Gly(32) bond. We
      investigated the localization of ET-1(1-31) in various hamster tissues by
      immunohistochemistry and compared it to the distribution of ET-1(1-21). We found
      that the localization and amount of ET-1(1-31) were different from those of ET
      1(1-21) in each tissue. ET-1(1-31)-like immunoreactivities (IR) in the heart,
      lung, and adrenal gland were observed in the same areas as ET-1(1-21) but were
      significantly weaker, suggesting that ET-1(1-31) might play a role only in mast
      cell/chymase-related pathological conditions in these tissues. In the liver, ET
      1(1-31)-like IR was strongly detected in Kupffer cells where ET-1(1-21)-like IR
      was seen more weakly. In the kidney, ET-1(1-31)-like IR was slightly higher than
      ET-1(1-21). These results suggest that ET-1(1-31) might have physiological roles
      distinct from those of ET-1(1-21) in some hamster tissues.

PMID- 14706575
TI  - Surgical ethics.

PMID- 14706576
TI  - Temporarily impaired surgeons and calling for help.
AB  - Surgeons who are ill must sometimes make their own judgments about their fitness
      to operate. The profession might consider more explicitly how surgeons make such
      judgments.

PMID- 14706577
TI  - Is ATLS a mechanism for teaching core competency in ethics?

PMID- 14706578
TI  - The cost of trauma center readiness.
AB  - BACKGROUND: Trauma centers and the services they provide are a unique and
      necessary component of our health system. By design trauma centers treat all
      injured patients regardless of their clinical or economic needs. The purpose of
      this study was to quantify the costs associated with the preparation of the
      capacity to provide trauma care at trauma centers within the State of Florida.
      METHODS: Utilizing a survey tool and multiple retreats, we assessed the
      capability of 20 verified trauma centers throughout the State of Florida. The
      survey focused on general attributes of each hospital, the costs associated with
      physician on call coverage, costs associated with verification, and lastly the
      costs associated with administration, outreach, and prevention. RESULTS: Data
      were acquired from 10 trauma centers. Ninety percent of the respondents pay on
      call coverage. The median annual physician compensation for on-call coverage was
      approximately 2.1 million US dollars. The total medial cost of readiness for each
      trauma center approximated 2.7 million US dollars annually. CONCLUSIONS: Trauma
      centers like fire departments and police services are required to be available 24
      hours a day, 7 days a week. This level of commitment by trauma centers and the
      reciprocal expectation from the community force trauma centers to make
      considerable investments in readiness. This cost of readiness is expended
      regardless of the patient volume or insurance status. Thus trauma centers have a
      large component of costs that are not captured by the traditional billing and
      cost accounting mechanisms within health systems and this fixed expense is
      extraordinarily difficult to recover given the current reimbursement environment.

PMID- 14706579
TI  - Carotid endarterectomy utilization and mortality in 10 states.
AB  - BACKGROUND: Studies that examined the rates of and mortality after carotid
      endarterectomy (CEA) mainly were confined to a limited geographical location or
      population. The primary purposes of this study are to examine the variation of
      risk-adjusted in-hospital mortality rates after CEA in 10 states, and utilization
      rates per capita of CEA. METHODS: An analysis was made of hospital discharge data
      from 10 states extracted from the Agency for Health Research and Quality national
      database, Healthcare Cost and Utilization Project (HCUP). RESULTS: The rates of
      CEA per capita were found to differ among the 10 states examined. No significant
      association was detected between geographic location and the adjusted risk of in
      hospital mortality. Sex, age, type of admission, and several comorbidities were
      found to be significant risk factors. CONCLUSIONS: Rates of CEA per capita differ
      among states. However, geographical location does not affect the likelihood of
      risk-adjusted mortality after the procedure.

PMID- 14706581
TI  - Optimal closure method of five-millimeter trocar sites.
AB  - BACKGROUND: Although many surgeons use absorbable sutures for skin closure of 5
      mm trocar sites, effective alternative materials exist. We compared 5-mm trocar
      site closures using a vicryl suture (VS), cyanoacrylate tissue adhesive (CTA), or
      skin tape (ST). METHODS: Patients rated wound pain and appearance at 1 and 6
      weeks after surgery. Seven surgeons masked to the closure method rated wound
      photographs at these time points using the Hollander wound evaluation scale.
      Logistic regression analysis was used to evaluate the ratings of each closure
      group. RESULTS: The 137 wounds of 48 patients undergoing laparoscopic procedures
      were randomized among three closure method groups. Patient demographics and
      procedure type were similar for all groups. Long closure times (>30 seconds) was
      significantly higher for VS compared with CTA and ST. Patients favored VS over ST
      and CTA at 1 week with respect to pain and wound appearance (P = 0.04 and P =
      0.02, respectively). They rated CTA closures more likely to have pain and poor
      wound appearance at 6 weeks (P = 0.05 and P = 0.03, respectively). Surgeons rated
      VS less likely (P = 0.02) and CTA more likely (P = 0.003) to show moderate to
      severe scar formation. Vicryl suture was less likely to have wound separation and
      edge inversion (P = 0.017 and P = 0.006, respectively). Cyanoacrylate tissue
      adhesive was more likely to yield step-off (P = 0.03), contour irregularities (P
      = 0.005), separation (P = 0.004), excessive distortion (P = 0.001), and edge
      inversion (P = 0.03). CONCLUSIONS: Although VS closure time of 5-mm trocar sites
      takes longer than CTA and ST, VS scar formation and comfort is superior to CTA
      and ST. Cyanoacrylate tissue adhesive yields poor results with respect to both
      wound healing and pain.

PMID- 14706580
TI  - Omeprazole is more effective than a histamine H2-receptor blocker for maintaining
      a persistent elevation of gastric pH after colon resection for cancer.
AB  - BACKGROUND: An assessment was made of the change and the effect of a histamine
      H(2)-receptor blocker (H(2)-blocker) or omeprazole on gastric pH after surgery.
      METHODS: Eighty patients who underwent colon resection for colorectal cancer were
      divided into groups of 20. Group I received neither H(2)-blocker nor omeprazole.
      Group II received cimetidine hydrochloride 1,200 mg daily, group III received
      ranitidine hydrochloride 200 mg daily, group IV received omeprazole 40 mg twice
      daily for 5 days. Gastric juice was measured preoperatively and then twice daily
      until the fifth postoperative day. RESULTS: The gastric pH decreased after
      surgery. The gastric pH increased on the first postoperative day after the
      administration of H(2)-blockers (P <0.001), but started to decrease on the second
      postoperative day. The gastric pH increased and remained high throughout the
      study period for the omeprazole group (P <0.001). CONCLUSIONS: The administration
      of an H(2)-blocker can significantly elevate the gastric pH value for patients
      after resection of colorectal cancer, but only lasts for 24 to 48 hours.
      Omeprazole is more effective than an H(2)-blocker at maintaining a persistent
      elevation of gastric pH.

PMID- 14706582
TI  - The effect of tissue adhesive, octyl-cyanoacrylate, on the healing of
      experimental high-risk and normal colonic anastomoses.
AB  - BACKGROUND: Tissue adhesives may be advantageous over sutures in colonic
      anastomoses because they do not result in potentially dangerous tight tissue
      approximation. METHODS: Ninety male Wistar-albino rats were used in the study.
      Excluding the 10 animals that constituted the control, the rest of the animals
      were divided in two groups: normal (N) and high-risk (HR). Only resection and
      anastomosis were done on half of the animals in each group. Octyl-cyanoacrylate
      was applied on the anastomosis of the other half of the groups. Anastomotic
      assessment was done at the third and seventh postoperative days. Gross
      anastomotic healing, mechanical strength, hydroxyproline deposition, and
      histopathological healing indices were used for the assessment. RESULTS: There
      was no difference in the third day and the seventh day groups regarding the gross
      healing parameters and hydroxyproline concentration. Similarly there was no
      difference between the third day groups in terms of mechanical healing (P =
      0.669). However, the mechanical strength of the anastomosis assessed the seventh
      postoperative day was lower in groups in which octyl-cyanoacrylate was applied (P
      <0.001). Furthermore, inflammatory reaction, presence of necrosis, peritonitis,
      and exudate was pronounced in groups in which octyl-cyanoacrylate was applied.
      CONCLUSIONS: Application of octyl-cyanoacrylate to both normal and high-risk
      colonic anastomosis does not provide any benefit over conventional suturing at
      the early phase of the healing. However, octyl-cyanoacrylate seems to be
      detrimental at the late phase of the healing probably due to the ongoing intense
      inflammatory reaction.

PMID- 14706583
TI  - Incidence and treatment of recurrent plantar fibromatosis by surgery and
      postoperative radiotherapy.
AB  - BACKGROUND: The incidence of plantar fibromatosis (PF) is unknown. Sometimes PF
      tends to recur repetitively after surgical treatment. In our institute we have
      used postoperative radiotherapy in an attempt to diminish the change on
      recurrence. METHODS: The Dutch Network and National Database for Pathology
      (PALGA) was consulted to establish the incidence of plantar fibromatosis (PF).
      Data from 9 patients (11 feet) with PF referred to our institute for recurrent
      disease were analyzed and the role of postoperative radiotherapy in prevention of
      recurrence was studied. RESULTS: An average of 1.2 operations for PF was
      performed per 100,000 citizens yearly in the Netherlands. Twenty-six operations
      were performed and postoperative radiotherapy was used in 6 cases. Plantar
      fasciectomy was associated with the lowest recurrence rate. After microscopically
      incomplete excision or excision of early recurrence (< or =6 months) alone all
      tumors recurred, while recurrence was rarely observed after adjuvant
      radiotherapy. However, radiotherapy was associated with significantly impaired
      functional outcome in 3 cases. CONCLUSIONS: Plantar fibromatosis is relatively
      rare. Plantar fasciectomy seems to be the operation of choice. Although effective
      in decreasing the recurrence rate, adjuvant radiotherapy should be used very
      selectively because of its serious side effects.

PMID- 14706584
TI  - Management of neuroendocrine liver metastases.
AB  - BACKGROUND: The optimum management of neuroendocrine liver metastases,
      particularly the role of liver transplantation is ill-defined. Current strategies
      are based on anecdotal reports and small retrospective studies, rather than
      prospective data. This, as well as the failure to standardize treatment, has
      probably contributed to the reported variations in outcome. DATA SOURCES: To
      formulate a putative management protocol and to reevaluate the role of liver
      transplantation in patients with neuroendocrine liver metastases, a review of the
      published literature (Medline search) was conducted. CONCLUSIONS: Isolated
      hepatic metastases should be resected when suitable. Chemoembolization of liver
      metastases should precede resection of bulky disease and be used to palliate
      those with unresectable disease. Radiofrequency ablation is suitable for smaller
      metastatic lesions (<3 cm diameter) in the liver. Systemic treatment with
      somatostatin analogues or radioactive metaiodobenzylguanidine (MIBG) is
      appropriate to reduce symptoms and slow disease progression, but prospective data
      is required to define their exact roles as adjuvant and therapeutic agents.
      Although current systemic chemotherapy, applied in isolation, may have a role in
      patients in whom other therapies have failed, its efficacy remains unproven.
      Restriction of liver transplantation to the treatment of patients with carcinoid
      metastases with biologically favorable features, limited tumor bulk and without
      systemic disease may make transplantation a curative rather than a palliative
      treatment option in selected patients.

PMID- 14706585
TI  - Factors that predict conversion in patients undergoing laparoscopic surgery for
      Crohn's disease.
AB  - BACKGROUND: To identify factors that would predict conversion in patients
      undergoing laparoscopic surgery for Crohn's disease. METHODS: Data were collected
      retrospectively. All procedures were performed by an experienced laparoscopic
      surgeon. RESULTS: Forty-eight patients underwent 57 laparoscopic procedures.
      Twenty-six of these procedures were for recurrent disease. The conversion rate
      was 42.3% (11 of 26) for recurrent disease and 13% (4 of 31) for primary disease.
      On univariate analysis age (P = 0.02), surgery for recurrence (P = 0.02), time
      from diagnosis (P = 0.03), and the presence of a clinical mass (P = 0.03) were
      factors that predicted conversion. On multivariate analysis these factors except
      time from diagnosis still remained significant. Patients who did not undergo a
      conversion had significantly better post operative outcomes. There was no
      difference in the incidence of major or minor complications or the number of
      resections in both groups. CONCLUSIONS: The conversion rate for the whole group
      was 28%. The rate is higher in patients who are over 40 years of age who are
      undergoing procedures for recurrence.

PMID- 14706586
TI  - Obesity and lymphatic mapping with sentinel lymph node biopsy in breast cancer.
AB  - BACKGROUND: With increasing sentinel lymph node experience, patient subsets
      associated with lower success rates are being identified. Obesity may be one such
      subset. METHODS: A retrospective review was conducted of breast cancer patients
      who underwent sentinel lymph node biopsy from March 1997 to September 2002.
      Factors examined included demographics, body mass index (BMI), breast size, tumor
      characteristics, lymphoscintigraphy drainage, and success of mapping. Chi-square
      and exact P values were used for statistical analysis. RESULTS: One hundred
      seventy-four breast cancer patients had sentinel lymph node biopsy. Sixty-seven
      patients were normal weight (BMI <25.1); 56 patients were overweight (BMI 25.1 to
      29.9); and 51 patients were obese (BMI >29.9). Failure to identify a sentinel
      lymph node and the false negative rate were not statistically different (P =
      0.7783 and P = 0.9290, respectively) among the three groups. CONCLUSIONS: Obesity
      has no significant effect on sentinel node identification rate or false negative
      rate.

PMID- 14706587
TI  - Personal management of 57 consecutive patients with esophageal perforation.
AB  - BACKGROUND: Esophageal perforation is a surgical emergency associated with high
      morbidity and mortality. There is no consensus regarding the appropriate
      management of this life-threatening condition. METHODS: A retrospective review
      was made of 57 patients with esophageal perforations treated at the Department of
      Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh,
      India, between September 1986 and December 2001. RESULTS: Forty-four (77%)
      perforations were due to iatrogenic causes, spontaneous perforations occurred in
      6 patients (11%). Foreign body ingestion caused perforation in 4 (7%), followed
      by blunt trauma in 2 (4%) and caustic injury in 1 patient. A total of 6 (11%)
      patients had cervical injury, 49 (86%) patients had thoracic, and 1 patient had
      abdominal esophageal injury. Thirty-three (58%) patients underwent emergency
      esophagectomy, 4 (7%) patients underwent primary repair, and 4 patients (7%)
      underwent drainage alone, whereas 16 (28%) patients were managed by nonoperative
      treatment. Using these treatment principles, we achieved 86% survival rate for
      all patients. Eight (14%) patients died. Spontaneous perforation had the highest
      mortality (67%). CONCLUSIONS: Esophageal perforation needs aggressive treatment.
      The treatment depends mainly on two factors: perforation in a healthy esophagus,
      and perforation with a preexisting underlying intrinsic esophageal disease
      causing distal obstruction. Esophageal perforation associated with stenotic
      lesions (benign or malignant) needs esophageal extirpation. Perforation in a
      healthy esophagus should be treated by primary closure if encountered early.
      Nonoperative conservative treatment is appropriate when esophageal perforation is
      encountered late.

PMID- 14706588
TI  - Impact of neoadjuvant therapy of perioperative morbidity in patients with
      esophageal cancer.
AB  - BACKGROUND: Conflicting results of preoperative radiochemotherapy in patients
      with esophageal cancer have been obtained; only patients with a complete
      pathological response seem to benefit from this therapy. However, there is
      evidence that preoperative radiochemotherapy leads to considerable postoperative
      morbidity. Therefore, postoperative morbidity was retrospectively investigated in
      82 patients with an esophageal cancer who received preoperative
      radiochemotherapy. METHODS: One hundred twenty-two consecutively operated on
      patients were included (1991 to 2001). Preoperative radiochemotherapy was
      initiated in 1994 for cT >1, cNx, cM0 regardless of histology (n = 82); 36 Gy was
      applied (1.8 Gy daily, days 1 to 5, weeks 1 to 4), concurrently 5-fluorouracil
      (500 mg/m(2) days 1 to 5, weeks 1 to 4), and cisplatin (20 mg/m(2) days 1 to 5,
      weeks 1 and 4). Postoperative morbidity was categorized as surgery- and
      nonsurgery-related morbidity. Survival was calculated by the Kaplan-Meier method.
      Results were stratified into histology and compared with patients who were
      operated on only (n = 40). RESULTS: Complete pathological response after
      preoperative radiochemotherapy was achieved in 22%. An increase in surgery
      related morbidity was observed after preoperative radiochemotherapy due to lesion
      of recurrent nerve (38% versus 12.5%, P = 0.009), as well as a marked difference
      in pulmonary morbidity (57% versus 37.5%, P = 0.05). The proportion of combined
      morbidity was increased after preoperative radiochemotherapy (49.4% versus 15%, P
      = 0.02), which led to a considerable prolongation of postoperative hospital stay
      (33 versus 21 days median, P = 0.0022). Patients with a longer postoperative
      hospital stay (>30 days; 43.2%) lived significantly shorter than patients with a
      shorter postoperative hospital stay (56.8%, P = 0.001). There was no statistical
      survival benefit in the neoadjuvant treated group. However, calculation of long
      term survival revealed a significant survival advantage in patients with squamous
      cell cancer and a complete pathological response compared with patients without
      response (median 642 days versus 302, P = 0.026). CONCLUSIONS: Perioperative
      morbidity was significantly increased after preoperative radiochemotherapy. Long
      term survival was clearly affected by the length of postoperative stay.
      Therefore, we need better patient selection for application of preoperative
      radiochemotherapy.

PMID- 14706589
TI  - Lymphedema after treatment of breast cancer.
AB  - BACKGROUND: Lymphedema is one of the major long-term complications of axillary
      dissection. This study was designed to investigate the risk factors that are
      predicted to effect the development of lymphedema after complete axillary
      dissection. METHODS: Two hundred forty patients who had undergone modified
      radical mastectomy with complete axillary dissection were examined at least 18
      months after the surgery. The effects of age, diabetes, smoking, hypertension,
      chemotherapy, radiotherapy, tamoxifen use, stage, body mass index, number of the
      removed and metastatic lymph nodes, and total volume of the wound drainage on the
      development of lymphedema were analyzed. RESULTS: Lymphedema developed in 68
      (28%) of the 240 cases. Axillary radiotherapy and body mass index were found to
      increase the incidence of the lymphedema. CONCLUSIONS: Women who had the
      combination of full axillary dissection and axillary radiotherapy carry a
      significant risk of lymphedema.

PMID- 14706590
TI  - Impact of a surgical oncologist on general surgery residency training program.
AB  - BACKGROUND: To assess the impact of adding a surgical oncologist to our faculty
      we examined the operative experience in our program before and after the
      addition. METHODS: Operative case numbers reported to the American Board of
      Surgery over a 10-year period were analyzed. This time period encompassed 5 years
      before and after the addition of a surgical oncologist to our faculty. All
      defined category case numbers were examined using t test analysis. Significance
      was defined as a P value of less than 0.05. RESULTS: The overall caseload
      increased in the time period after the faculty addition. There was a
      statistically significant increase in skin/soft tissue, breast, esophagus, small
      intestine, large intestine, live, spleen, and endocrine cases. No statistical
      significance was seen in head/neck, stomach, pancreas, and biliary cases.
      CONCLUSIONS: The addition of a surgical oncologist to our faculty coincides with
      a statistically significant increase in areas of skin/soft tissue, breast,
      esophagus, small intestine, large intestine, liver, spleen, and endocrine. Other
      areas not statistically significant may reflect referral patterns or this
      particular oncologist's preferences of practice.

PMID- 14706591
TI  - Relationship between gastrointestinal transit time and daily stool frequency in
      patients after Ileal J pouch-anal anastomosis for ulcerative colitis.
AB  - BACKGROUND: To investigate how the gastrointestinal transit function changes
      after ileal J pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) and to
      study whether gastrointestinal transit time (GTT) has an influence on daily stool
      frequency, we investigated the relationship between GTT and stool frequency per
      day. METHODS: Forty patients with UC who had undergone restorative
      proctocolectomy, with ileostomy closure at least 48 to 120 months (mean 96.3)
      previously, and who had no preoperative and postoperative complications were
      recruited. They were divided into two groups on the basis of their stool
      frequency: 26 patients had a stool frequency of less than 6 times per day (group
      A: 16 men, 10 women; aged 15 to 59 years old, average 36.6) and 14 patients had a
      stool frequency of 7 or more times per day (group B: 10 men, 4 women; 24 to 56
      years old, average 40.9). The GTTs using a radiopaque marker were studied.
      Interviews concerning the defecation states were performed at the examination.
      RESULTS: High nocturnal stool frequency was significantly noted more in group B
      than in group A (P <0.001). All cases in group A and 12 cases in group B could
      discriminate flatus from feces, and there were significant differences between
      groups A and B (P <0.05). Feeling of stool remaining was significantly noted more
      in group B than in group A (P <0.01). Stool consistency in group A was harder
      than that in group B (P <0.001). Patients with soiling were significantly noted
      more in group B compared with those in group A (P <0.001). Incontinence was
      detected in only 2 cases in group B. Group A showed a better defecation state
      than group B. In the GTT study, the GTT was almost the same in groups A and B.
      The small bowel transit, pouch transit, and whole gut transit times in group B
      were faster than those of group A (P <0.001). Removal length of the terminal
      ileum in patients after IPAA: patients in group B (13.8 +/- 3.9 cm) had
      significantly more ileum removed compared with patients in group A (6.3 +/- 2.4
      cm; P <0.001). Regression lines in the relationship between removal length of the
      terminal ileum and individual stool frequency showed there was a correlation
      between removal length of the terminal ileum and individual stool frequency per
      day in direct proportion (r = 0.79, P <0.001). A resection of more ileum, up to
      15 cm, plays a role in increased stool frequency. CONCLUSIONS: The present
      results suggested that rapid transit of both the small bowel and pouch may lead
      to a high stool frequency of 7 or more times per day with a poor defecation state
      after IPAA. It was also pointed out in this study that an important point is a
      resection of more ileum, up to 15 cm, plays a role in increased stool frequency.

PMID- 14706592
TI  - Predictors of development of anastomotic femoral pseudoaneurysms after
      aortobifemoral reconstruction for abdominal aortic aneurysm.
AB  - BACKGROUND: The pathogenesis of anastomotic femoral pseudoaneurysms (AFPs) is
      still unclear. We have performed this long-term retrospective study of patients
      who underwent aortobifemoral reconstruction for abdominal aortic aneurysm (AAA)
      in order to better establish the long-term rate of AFP and to identify the
      predictors of its late occurrence. METHODS: The long-term outcome of 178 patients
      who underwent and survived aortobifemoral reconstruction for infrarenal AAA was
      reviewed. RESULTS: During a median follow-up of 5.2 years, 28 AFPs developed in
      19 patients. Six AFPs were recurrent. The mean linearized rate of AFPs was 1.88%
      per year. At 15 years, the survival-freedom rate from AFPs was 60%, and from
      repair of AFPs it was 62%. The survival-freedom rate from AFP was significantly
      poorer in patients with chronic obstructive pulmonary disease (P = 0.017; at 10
      years: 64.3% versus 92.3%), hyperlipidemia (P = 0.0056; at 10 years: 59.2% versus
      87.5%), current smoking (P <0.0001; at 10 years: 65.8% versus 94.5%), and
      postoperative inguinal wound infection (P <0.0001; at 10 years: 42.8% versus
      86.8%). Multivariate analysis showed that chronic obstructive pulmonary disease
      (relative risk [RR]: 3.05, 95% confidence interval [CI]: 1.04 to 8.95), current
      smoking (RR: 5.38, 95% CI: 1.62 to 17.90), and postoperative inguinal wound
      infection (RR: 9.04, 95% CI: 2.76 to 29.96) were significantly associated with
      the development of AFPs. The linearized rate of AFPs was significantly higher
      only among current smokers (P <0.0001, 4.4% versus 0.8% per year) and among those
      who had inguinal wound infection (P = 0.001, 9.2% versus 1.5% per year).
      CONCLUSIONS: Current smoking and inguinal wound infection may contribute to the
      development of AFP after aortobifemoral reconstruction for AAA, likely by
      affecting reparative connective tissue mechanisms at the anastomotic site.

PMID- 14706593
TI  - Robotic assisted rectopexy.
AB  - BACKGROUND: During the last 3 years, robotic surgery has had a considerable
      impact on minimally invasive surgery in a wide range of specialties. This study
      describes the surgical technique and preliminary results of our first 6 cases of
      robotic assisted suture rectopexy. METHODS: During a period of 13 months 6
      patients with full thickness rectal prolapse were operated on with the da Vinci
      surgical system. All patients were considered suitable for a suture rectopexy.
      Setting-up time, procedure time, patient recovery, and hospital stay were
      recorded and compared with the current literature. RESULTS: All operations were
      completed successfully using the robotic system. There were no major
      complications and no deaths. Mean setting-up time was 28 minutes, mean operation
      time was 127 minutes, and mean hospital stay was 6 days. At 3 to 6 months of
      follow-up all patients are in good health, with no signs of recurrence and no
      reports of constipation. CONCLUSIONS: Robotic assisted suture rectopexy is
      feasible and safe and apparently meets accepted standards of laparoscopic
      surgery.

PMID- 14706594
TI  - Improvement of intestinal motility using S-methylisothiourea in postoperative
      ileus.
AB  - BACKGROUND: The inflammatory mediator nitric oxide (NO) plays an important role
      in postoperative gastrointestinal motility. METHODS: Using S-methylisothiourea
      sulfate (SMT), a selective inducible nitric oxide synthase inhibitor, we studied
      the physiological role of the endogenous NO in the modulation of intestinal
      motility. The study was performed in vivo in a canine postoperative model. Ten
      mongrel dogs were treated with a continuous intravenous infusion of SMT after a
      surgical intestinal manipulation. Small intestine transit time was
      fluoroscopically measured using barium sulfate as it passed through a gastrostomy
      tube on postoperative days (POD) 1, 2, and 3. RESULTS: Average transit times on
      POD 1 in the 4 mg/kg/h and 2 mg/kg/h SMT groups significantly decreased compared
      with that of the saline group. However, the transit times on POD 2 and 3 were not
      significantly different among the three groups. CONCLUSIONS: S-methylisothiourea
      sulfate improves small intestine motility at an early postoperative stage.

PMID- 14706595
TI  - Posttraumatic dissecting aneurysm of the superior mesenteric artery.

PMID- 14706596
TI  - Eloesser procedure for postpneumonectomy bronchopleural fistula.

PMID- 14706597
TI  - The superior rectal artery and its branching pattern with regard to its clinical
      influence on ligation techniques for internal hemorrhoids.
AB  - BACKGROUND: The hemorrhoidal artery ligation has been used for submucosal
      ligation of hemorrhoidal arteries by means of an ultrasonographic transducer
      since 1995. The success of this technique depends on the submucosal course of
      these arteries. Our investigation deals with branches of the superior rectal
      artery which pierce the rectal wall where they cannot be reached by this method.
      METHODS: The branching patterns were investigated by means of 5 macroscopic
      preparations of adult pelves, histological section series of 35 fetal and 3 adult
      pelves impregnated in epoxy-resin, and transperineal color Doppler ultrasound of
      7 proctologic patients and 28 volunteers. RESULTS: Additional branches of the
      superior rectal artery coursing in outer layers of the rectal wall were shown
      entering the rectal wall just above the levator ani muscle to supply the internal
      hemorrhoidal plexus (corpus cavernosum recti). CONCLUSIONS: The terminal course
      of the branches of the superior rectal artery is not only applied to the rectal
      submucosa. We have shown that additional branches may be detected by
      ultrasonography and should be taken into account by the operating surgeon.

PMID- 14706598
TI  - Three-dimensional computer images of Morgagni hernia.

PMID- 14706599
TI  - Fondaparinux sodium lacks immunomodulatory effects of heparin.
AB  - BACKGROUND: Venous thromboembolism (VTE) remains a frequent complication in
      orthopedic and trauma patients, despite the use of prophylactic antithrombotic
      drugs like standard or low molecular weight heparin. A new synthetic
      pentasaccharide with specific anti-Xa activity (fondaparinux sodium) has been
      shown to reduce the overall risk of VTE in major orthopedic surgery by 50%
      without increasing the risk of clinically relevant bleeding, when compared with
      enoxaparin. Beyond their traditional role as anticoagulants, heparin and low
      molecular weight heparin possess potent immunomodulatory effects. For example,
      heparin and enoxaparin enhance endotoxin (lipopolysaccharide)-induced cytokine
      production in isolated human monocytes and in whole blood. In this study, we
      investigated the immunomodulatory effects of heparin and fondaparinux sodium.
      METHODS: Treatment of whole blood from 5 healthy volunteers ex vivo with heparin,
      fondaparinux sodium, and LPS (10 ng/mL, 4 hours). Determination of plasma
      interleukin (IL)-8 levels, thrombin clotting times, and anti-Xa activity with
      enzyme-linked immunosorbent assay and the AMAX CS190 device, respectively.
      Statistical analysis by analysis of variance and Fisher's probable least-squares
      difference posthoc test. RESULTS: Heparin concentrations > or =20 IU/mL
      significantly increased LPS-induced IL-8 production. Fondaparinux sodium,
      however, did not increase the LPS response. Heparin and fondaparinux sodium
      exhibited the expected anticoagulatory activities: heparin increased both
      thrombin clotting time and anti-Xa activity, fondaparinux sodium increased anti
      Xa activity only. CONCLUSIONS: Fondaparinux sodium is not an immunomodulator like
      heparin, suggesting that this novel compound may lack adverse effects in
      endotoxemic patients. Further studies will establish whether fondaparinux sodium
      can safely be administered to patients with endotoxemia or sepsis.

PMID- 14706600
TI  - Cognitive task analysis for teaching technical skills in an inanimate surgical
      skills laboratory.
AB  - BACKGROUND: The teaching of surgical skills is based mostly on the traditional
      "see one, do one, teach one" resident-to-resident method. Surgical skills
      laboratories provide a new environment for teaching skills but their
      effectiveness has not been adequately tested. Cognitive task analysis is an
      innovative method to teach skills, used successfully in nonmedical fields. The
      objective of this study is to evaluate the effectiveness of a 3-hour surgical
      skills laboratory course on central venous catheterization (CVC), taught by the
      principles of cognitive task analysis to surgical interns. METHODS: Upon arrival
      to the Department of Surgery, 26 new interns were randomized to either receive a
      surgical skills laboratory course on CVC ("course" group, n = 12) or not
      ("traditional" group, n = 14). The course consisted mostly of hands-on training
      on inanimate CVC models. All interns took a 15-item multiple-choice question test
      on CVC at the beginning of the study. Within two and a half months all interns
      performed CVC on critically ill patients. The outcome measures were cognitive
      knowledge and technical-skill competence on CVC. These outcomes were assessed by
      a 14-item checklist evaluating the interns while performing CVC on a patient and
      by the 15-item multiple-choice-question test, which was repeated at that time.
      RESULTS: There were no differences between the two groups in the background
      characteristics of the interns or the patients having CVC. The scores at the
      initial multiple-choice test were similar (course: 7.33 +/- 1.07, traditional: 8
      +/- 2.15, P = 0.944). However, the course interns scored significantly higher in
      the repeat test compared with the traditional interns (11 +/- 1.86 versus 8.64 +/
      1.82, P = 0.03). Also, the course interns achieved a higher score on the 14-item
      checklist (12.6 +/- 1.1 versus 7.5 +/- 2.2, P <0.001). They required fewer
      attempts to find the vein (3.3 +/- 2.2 versus 6.4 +/- 4.2, P = 0.046) and showed
      a trend toward less time to complete the procedure (15.4 +/- 9.5 versus 20.6 +/-
      9.1 minutes, P = 0.149). CONCLUSIONS: A surgical skills laboratory course on CVC,
      taught by the principles of cognitive task analysis and using inanimate models,
      improves the knowledge and technical skills of new surgical interns on this task.

PMID- 14706601
TI  - Assessment of critical appraisal skills.
AB  - BACKGROUND: Studies have provided little evidence that critical appraisal skills
      improve with focused courses. However, outcome measures in these studies have
      been questionable. The goal of this study was to develop a feasible, reliable,
      and valid assessment of critical appraisal skills. METHODS: Forty-four surgery
      residents read three articles and then responded to short answer questions and
      provided 7-point ratings regarding various methodological aspects of each
      article. Reliability and validity of the examination were assessed. RESULTS: The
      mean score was 52.4% (SD 8.6%). Internal consistency of the 55-question
      examination was 0.77. Interrater reliability of clinician markers was 0.91. Mean
      score for residents with more intensive critical appraisal training was
      significantly higher than for those with little or no training (56.6% versus
      49.3%, t(35) = 2.31, P = 0.02), suggesting construct validity. CONCLUSIONS: This
      examination has promising psychometric properties, and may be useful in
      evaluating critical appraisal curricula.

PMID- 14706602
TI  - Improving the adverse changes in cardiac autonomic nervous control during
      laparoscopic surgery, using an intermittent sequential pneumatic compression
      device.
AB  - BACKGROUND: The creation of positive pressure pneumoperitoneum (PP) may lead to
      adverse cardiovascular effects during laparoscopic operations. It can also lead
      to increased sympathetic cardiac activity, that might have serious consequences.
      We hypothesized that by reversing the hemodynamic effects, the use of
      intermittent sequential pneumatic compression device (Lympha-press) on the lower
      extremities would lead to improved cardiac autonomic control. METHODS: This was a
      prospective cohort study, in which patients served as their own control. Fifteen
      patients without cardiorespiratory disease undergoing elective laparoscopic
      cholecystectomy were enrolled prospectively. The activity of the cardiac
      autonomic nervous system was evaluated by using spectral analysis of heart rate
      variability, with the Del Mar Avionics 363 (Irvine, California), based on the
      fast Fourier transformation. The Lympha-press was manipulated several minutes
      after induction of PP. In each frequency band we measured and compared the power
      values during anesthesia against those of PP, as well as those of PP against
      those recorded during activation of Lympha-press. RESULTS: Creation of PP caused
      increased sympathetic activity, as was manifested by increased power of the low
      frequency band. Manipulation of the Lympha-Press compression device caused
      increased parasympathetic activity, as was evident by significant increased power
      of the high frequency band in all patients. CONCLUSIONS: Using an intermittent
      sequential pneumatic compression device during laparoscopic cholecystectomy may
      improve cardiac autonomic control by enhancing protective parasympathetic
      activity. That may have clinical significance, especially in patients suffering
      from cardiac disease, by improving heart rate variability and elevating the
      threshold of the occurrence of ventricular arrhythmia.

PMID- 14706603
TI  - Multipurpose extended subcostal incision for hepatobiliary surgery.
AB  - Exposure is especially important for procedures performed on the liver and
      biliary tract where careful, precise anatomic dissection of vascular and biliary
      structures is required. We describe a modified subcostal incision that provides
      both safe exposure and versatility for most hepatobiliary procedures.

PMID- 14706604
TI  - A modification of segment III intrahepatic cholangiojejunostomy.
AB  - Segment III bypass can achieve excellent palliation in jaundiced patients with
      unresectable malignancy of the hepatic duct confluence. However, the long-term
      benefits are often offset by early morbidity and mortality associated with
      surgery. Bile leakage is a common postoperative complication. Several approaches
      to the segment III duct have been described. The "round ligament approach"
      identifies the segment III duct by following the round ligament into the recessus
      of Rex, in the umbilical fissure. It is the approach adopted by most units,
      including our own. The liver is often split to a depth of 5 to 6 cm to expose the
      duct. Fashioning an intrahepatic cholangiojejunostomy within the recess of the
      umbilical fissure can be technically difficult due to lack of space. We describe
      a modification of the round ligament approach, creating a long and tension-free
      cholangiojejunostomy, which we believe reduces the incidence of postoperative
      bile leakage.

PMID- 14706605
TI  - A consensus statement on empiric therapy for suspected gram-positive infections
      in surgical patients.
AB  - BACKGROUND: Multidrug resistance among gram-positive pathogens in tertiary and
      other care centers is common. A systematic decision pathway to help select
      empiric antibiotic therapy for suspected gram-positive postsurgical infections is
      presented. DATA SOURCES: A Medline search with regard to empiric antibiotic
      therapy was performed and assessed by the 15-member expert panel. Two separate
      panel meetings were convened and followed by a writing, editorial, and review
      process. CONCLUSIONS: The main goal of empiric treatment in postsurgical patients
      with suspected gram-positive infections is to improve clinical status. Empiric
      therapy should be initiated at the earliest sign of infection in all critically
      ill patients. The choice of therapy should flow from beta-lactams to vancomycin
      to parenteral linezolid or quinupristin-dalfopristin. In patients likely to be
      discharged, oral linezolid is an option. Antibiotic resistance is an important
      issue, and in developing treatment algorithms for reduction of resistance, the
      utility of these new antibiotics may be extended and reduce morbidity and
      mortality.

PMID- 14706608
TI  - Repair techniques for major incisional hernias.

PMID- 14706610
TI  - Laser therapy for small breast cancers.

PMID- 14706612
TI  - Operative risk of rectal cancer surgery in the elderly.

PMID- 14706614
TI  - Pancreaticojejunostomy with invagination of spatulated pancreatic stump into a
      jejunal pouch.

PMID- 14706616
TI  - Mathematical modelling of skeletal repair.
AB  - Tissue engineering offers significant promise as a viable alternative to current
      clinical strategies for replacement of damaged tissue as a consequence of disease
      or trauma. Since mathematical modelling is a valuable tool in the analysis of
      complex systems, appropriate use of mathematical models has tremendous potential
      for advancing the understanding of the physical processes involved in such tissue
      reconstruction. In this review, the potential benefits, and limitations, of
      theoretical modelling in tissue engineering applications are examined with
      specific emphasis on tissue engineering of bone. A central tissue engineering
      approach is the in vivo implantation of a biomimetic scaffold seeded with an
      appropriate population of stem or progenitor cells. This review will therefore
      consider the theory behind a number of key factors affecting the success of such
      a strategy including: stem cell or progenitor population expansion and
      differentiation ex vivo; cell adhesion and migration, and the effective design of
      scaffolds; and delivery of nutrient to avascular structures. The focus will be on
      current work in this area, as well as on highlighting limitations and suggesting
      possible directions for future work to advance health-care for all.

PMID- 14706617
TI  - Isomerization and apparent DNA bending by pi, the replication protein of plasmid
      R6K.
AB  - Plasmid R6K-encoded pi protein has multiple regulatory functions in replication
      and transcription. These functions rely, in part, on a complex set of
      interactions between monomers and dimers of the protein and distinct DNA targets,
      the direct and inverted repeats (DRs, IRs). In the work described here, we
      examine the isomerization and DNA bending properties of pi using electrophoretic
      mobility shift assays and circular permutation assays. Our data suggest that pi
      dimers can bend IRs, and dimer subunits seem to readily associate in head-to-head
      and head-to-tail fashion. The ability of pi to bend DRs is also reexamined using
      techniques that allow us to discriminate between bending induced by its different
      isomeric forms. We find that both monomers and dimers bend a single DR to similar
      degrees while results with 2DRs are more complex. The significance of the bending
      data in regard to a possible mechanism for replication initiation by pi protein
      is discussed.

PMID- 14706618
TI  - Activation of beta-catenin-TCF-mediated transcription by non-receptor tyrosine
      kinase v-Src.
AB  - Activation of Wnt signaling is an early event in colorectal tumorigenesis, while
      aberrant activation of non-receptor tyrosine kinase c-Src occurs during tumor
      progression. Here, we show that v-Src and receptor tyrosine kinase ErbB2 activate
      beta-catenin-TCF-mediated transcription. The effect of v-Src was abrogated by a
      dominant-negative mutant of TCF and the tumor suppressor APC. Furthermore, the
      effect of v-Src was partially abrogated by a dominant-negative mutant of MAP
      kinase, suggesting that v-Src exerts its effect at least in part via the MAP
      kinase pathway. Our finding raises the possibility that aberrantly activated c
      Src may enhance Wnt signaling and this may contribute to tumor progression.

PMID- 14706619
TI  - Interaction of peptide substrate outside the active site influences catalysis by
      CaMKII.
AB  - The interaction of calcium/calmodulin-dependent protein kinase II (CaMKII) with
      the NR2B subunit of N-methyl-D-aspartate-type glutamate receptor is thought to be
      one of the important events leading to synaptic plasticity. CaMKII binds NR2B by
      its catalytic site and by the autophosphorylation site binding pocket (APBP), a
      non-catalytic site. Mutagenesis of Glu-236, a residue in the APBP of CaMKII that
      is likely to be interacting with NR2B, influences phosphorylation of NR2B. The
      phosphorylation of syntide-2, a classical catalytic site substrate of CaMKII, is
      influenced to a much lesser extent by this mutation. Taken together these results
      indicate that interaction of NR2B at the non-catalytic site of CaMKII influences
      catalysis. Our data suggest that kinetic models of peptide substrate
      phosphorylation by CaMKII should incorporate the non-catalytic mode of binding of
      peptides that is dependent on the sequence of the peptide.

PMID- 14706621
TI  - Guideline to reference gene selection for quantitative real-time PCR.
AB  - Today, quantitative real-time PCR is the method of choice for rapid and reliable
      quantification of mRNA transcription. However, for an exact comparison of mRNA
      transcription in different samples or tissues it is crucial to choose the
      appropriate reference gene. Recently glyceraldehyde 3-phosphate dehydrogenase and
      beta-actin have been used for that purpose. However, it has been reported that
      these genes as well as alternatives, like rRNA genes, are unsuitable references,
      because their transcription is significantly regulated in various experimental
      settings and variable in different tissues. Therefore, quantitative real-time PCR
      was used to determine the mRNA transcription profiles of 13 putative reference
      genes, comparing their transcription in 16 different tissues and in CCRF-HSB-2
      cells stimulated with 12-O-tetradecanoylphorbol-13-acetate and ionomycin. Our
      results show that "Classical" reference genes are indeed unsuitable, whereas the
      RNA polymerase II gene was the gene with the most constant expression in
      different tissues and following stimulation in CCRF-HSB-2 cells.

PMID- 14706620
TI  - Prion protein suppresses perturbation of cellular copper homeostasis under
      oxidative conditions.
AB  - Prion protein (PrP) binds copper and exhibits superoxide dismutase-like activity,
      while the roles of PrP in copper homeostasis remain controversial. Using Zeeman
      graphite furnace atomic absorption spectroscopy, we quantified copper levels in
      immortalized PrP gene (Prnp)-deficient neuronal cells transfected with Prnp
      and/or Prnd, which encodes PrP-like protein (PrPLP/Dpl), in the presence or
      absence of oxidative stress induced by serum deprivation. In the presence of
      serum, copper levels were not significantly affected by the expression of PrP
      and/or PrPLP/Dpl, whereas serum deprivation induced a decrease in copper levels
      that was inhibited by PrP but not by PrPLP/Dpl. The inhibitory effect of PrP on
      the decrease of copper levels was prevented by overexpression of PrPLP/Dpl. These
      findings indicate that PrP specifically stabilizes copper homeostasis, which is
      perturbed under oxidative conditions, while PrPLP/Dpl overexpression prevents PrP
      function in copper homeostasis, suggesting an interaction of PrP and PrPLP/Dpl
      and distinct functions between PrP and PrPLP/Dpl on metal homeostasis. Taken
      together, these results strongly suggest that PrP, in addition to its antioxidant
      properties, plays a role in stabilizing cellular copper homeostasis under
      oxidative conditions.

PMID- 14706622
TI  - Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of
      the heat shock response in HeLa cells.
AB  - It has been established that non-steroidal anti-inflammatory drugs (NSAIDs), such
      as sodium salicylate, sulindac, ibuprofen, and indomethacin, induce anti
      inflammatory and anti-proliferative effects independent of cyclooxygenase. These
      cyclooxygenase-independent pharmacodynamic effects appear to regulate several
      signaling pathways involving proliferation, apoptosis, and heat shock response.
      However, the mechanisms of these actions remain an area of ongoing investigation.
      Hsc70 is a cytoplasmic chaperone protein involved in folding and trafficking of
      client proteins to different subcellular compartments, plays roles in signal
      transduction and apoptosis processes, and translocates to the nucleus following
      exposure to heat shock. Since NSAIDs induce some aspects of the heat shock
      response, we hypothesized that they may also induce Hsc70 nuclear translocation.
      Western immunoblotting and indirect cellular immunofluorescence showed that
      indomethacin and ibuprofen induce Hsc70 nuclear translocation at concentrations
      previously shown to induce HSF DNA-binding activity. Chemical inhibition of both
      p38(MAPK) and Erk42/44 had no effect on localization patterns. In addition, while
      indomethacin has been shown to behave as an oxidative stressor, the radical
      scavenging agent, N-acetyl cysteine, did not inhibit nuclear translocation. These
      results indicate that induction of the heat shock response by NSAIDs occurs at
      concentrations fivefold greater than those required to inhibit cyclooxygenase
      activity, suggesting a cyclooxygenase-independent mechanism, and in the presence
      or absence of kinase inhibitors and a free radical scavenger, suggesting
      independence of Erk42/44 or p38(MAPK) activities and intracellular oxidoreductive
      state.

PMID- 14706623
TI  - Osteogenic and chondrogenic differentiation by adipose-derived stem cells
      harvested from GFP transgenic mice.
AB  - Recent studies suggest that human adipose tissue contains pluripotent stem cells
      similar to bone marrow-derived stem cells. Taking advantage of homogeneously
      marked cells from green fluorescent protein (GFP) transgenic mice, we have
      previously demonstrated that bone marrow-derived stromal cells (BSCs)
      differentiate into a variety of cell lineages both in vitro and in vivo. In the
      present study, we extend this approach to characterize adipose tissue-derived
      stromal cells, sometimes called processed lipoaspirate (PLA) cells. Adipose
      derived stromal cells (ASCs) were isolated from inguinal fat pads of GFP
      transgenic mice after extensive washing with phosphate-buffered saline and
      treatment with collagenase. After primary culture in a control medium (Dulbecco's
      modified Eagle's medium+10% fetal bovine serum) and expansion to two passages,
      the cells were incubated in either an osteogenic medium (Dulbecco's modified
      Eagle's medium+10% fetal bovine serum+dexamethasone+ascorbate-2-phosphate+beta
      glycerophosphate) or a chondrogenic medium (Dulbecco's modified Eagle's medium+1%
      fetal bovine serum+insulin+ascorbate-2-phosphate+transforming growth factor
      beta1) for 2-4 weeks to induce osteogenesis and chondrogenesis, respectively.
      Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase
      staining, while chondrogenic differentiation was assessed by Alcian blue
      staining. Expression of osteocyte specific osteopontin, osteocalcin, and alkaline
      phosphatase, and chondrocyte specific aggrecan and type II/X collagen was
      confirmed by RT-PCR. ASCs incubated in the osteogenic medium were stained
      positively for von Kossa and alkaline phosphatase staining. Expression of
      osteocyte specific genes, except osteocalcin, was also detected. Incubation with
      chondrogenic medium induced Alcian blue positive cells and expression of aggrecan
      and type II/X collagen genes. No osteochondrogenic differentiation was observed
      in cells incubated in the control medium. ASCs from GFP transgenic mice have both
      osteogenic and chondrogenic potential in vitro. Since this cell population can be
      easily identified through fluorescence microscopy, it may be an ideal source of
      ASCs for further experiments on stem cell biology and tissue engineering.

PMID- 14706624
TI  - Assembly of fluorescent chimeric virus-like particles of canine parvovirus in
      insect cells.
AB  - Canine parvovirus (CPV) is a small non-enveloped ssDNA virus composed of the
      viral proteins VP1, VP2, and VP3 with a T=1 icosahedral symmetry. VP2 is nested
      in VP1 and the two proteins are produced by differential splicing of a primary
      transcript of the right ORF of the viral genome. The VP2 protein can be further
      proteolytically cleaved to form VP3. Previous studies have shown that VP1 and VP3
      are unnecessary for capsid formation and consequently, that VP2 alone is
      sufficient for assembly. We have hypothesized that insertion of the enhanced
      green fluorescent protein (EGFP) at the N-terminus of VP2 could be carried out
      without altering assembly. To investigate the possibility to develop fluorescent
      virus-like particles (fVLPs) from such chimeric VP2 proteins, the corresponding
      fusion construct was abundantly expressed in insect cells. Confocal imaging
      indicated that the EGFP-VP2 fusion product was assembled to fluorescent capsid
      like complexes. In addition, electron micrographs of purified EGFP-VP2 complexes
      showed that they displayed a very similar size and appearance when compared to
      VP2 VLPs. Further, immunolabelling of purified EGFP-VP2 VLPs showed the presence
      of EGFP within the structure. Fluorescence correlation spectroscopy (FCS) studies
      confirmed that fVLPs were very similar in size when compared to authentic CPV.
      Finally, feeding of mammalian cells susceptible to CPV infection with these fVLPs
      indicated that entry and intracellular trafficking could be observed. In summary,
      we have developed fluorescent virus-like nanoparticles carrying a heterologous
      entity that can be utilized as a visualization tool to elucidate events related
      to a canine parvovirus infection.

PMID- 14706625
TI  - Molecular cloning and characterization of a novel gene, EMILIN-5, and its
      possible involvement in skeletal development.
AB  - By analyzing expression profiles of human mesenchymal stem cells incubated in
      osteogenic supplements, we identified and characterized a novel human cDNA,
      elastin microfibril interface located protein-5 (EMILIN-5), that is likely to
      play a significant role in the process of osteogenesis. The deduced EMILIN-5
      product consists of 766 amino acids with a cysteine-rich EMI domain at the NH(2)
      terminus. Western blotting detected EMILIN-5 expression in a variety of
      osteoblastic cell lines. Immunohistochemistry of mouse embryos 13.5 days post
      coitus revealed relatively high levels of EMILIN-5 protein in perichondrium cells
      of developing limbs. Our findings suggest that the EMILIN-5 gene plays an
      important role in skeletal development.

PMID- 14706626
TI  - Cloning of a novel phospholipase C-delta isoform from pacific purple sea urchin
      (Strongylocentrotus purpuratus) gametes and its expression during early embryonic
      development.
AB  - Calcium (Ca(2+)) is a ubiquitous intracellular messenger, controlling a diverse
      range of cellular processes, including fertilization and development of the
      embryo. One of the key mechanisms involved in triggering intracellular calcium
      release is the generation of the second messenger inositol-1,4,5-phosphate
      (IP(3)) by the phospholipase C (PLC) class of enzymes. Although five distinct
      forms of PLC have been identified in mammals (beta, gamma, delta, epsilon, and
      zeta), only one, PLCgamma, has thus far been detected in echinoderms. In the
      present study, we describe the isolation of a cDNA encoding a novel PLC isoform
      of the delta (delta) subclass, PLC-deltasu, from the egg of the Pacific purple
      sea urchin Strongylocentrotus purpuratus. We also demonstrate the presence of
      this PLC within the sperm and in the early embryo. The PLC-deltasu cDNA (2.44kb)
      encodes a 742 amino acid polypeptide with an open reading frame of 84.6kDa and a
      pI of 6.04. All of the characteristic domains found in mammalian PLCdelta
      isoforms (PH domain, EF hands, an X-Y catalytic region, and a C2 domain) are
      present in PLC-deltasu. A homology search revealed that PLC-deltasu shares most
      sequence identity with bovine PLCdelta2 (39%). We present evidence that PLC
      deltasu is expressed in unfertilized eggs, fertilized eggs, and in the early
      embryo. In addition to Northern and polymerase chain reaction (PCR) analyses, in
      situ hybridization experiments further demonstrated that the embryonic regions
      within which the PLC-deltasu transcript can be detected during early embryonic
      development are associated with the highest levels of proliferative activity,
      suggesting a possible involvement with metabolism or cell cycle regulation.

PMID- 14706627
TI  - Induction of gicerin/CD146 in the rat carotid artery after balloon injury.
AB  - Gicerin is a cell adhesion molecule belonging to the immunoglobulin superfamily.
      It is reported that the human homologous molecule, CD146, is expressed in the
      endothelial cells. Here, we found that the expression of gicerin was increased in
      the rat carotid arteries after balloon injury. Immunohistochemical analysis
      demonstrated that the expression of gicerin protein was increased in the medial
      smooth muscle cells prior to the formation of neointima one week after the injury
      and was also increased in the luminal edge of the neointima after two weeks. We
      employed A10 cells, a cell line derived from rat aortic smooth muscle cell, and
      examined the effect of growth factors on the expression of gicerin, such as IGF
      1, PDGF-BB, and bFGF. We found that IGF-1, but not PDGF-BB and bFGF,
      significantly increases the expression of gicerin protein in A10 cells. These
      suggest gicerin might be involved in the arteriosclerotic neointima formation in
      the artery.

PMID- 14706628
TI  - Structures of human purine nucleoside phosphorylase complexed with inosine and
      ddI.
AB  - Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme which plays a
      key role in the purine salvage pathway, and PNP deficiency in humans leads to an
      impairment of T-cell function, usually with no apparent effect on B-cell
      function. PNP is highly specific for 6-oxopurine nucleosides and exhibits
      negligible activity for 6-aminopurine nucleosides. The catalytic efficiency for
      inosine is 350,000-fold greater than for adenosine. Adenine nucleosides and
      nucleotides are deaminated by adenosine deaminase and AMP deaminase to their
      corresponding inosine derivatives which, in turn, may be further degraded. Here
      we report the crystal structures of human PNP in complex with inosine and
      2('),3(')-dideoxyinosine, refined to 2.8A resolution using synchrotron radiation.
      The present structures provide explanation for ligand binding, refine the purine
      binding site, and can be used for future inhibitor design.

PMID- 14706629
TI  - Wnt proteins promote neuronal differentiation in neural stem cell culture.
AB  - Wnt signaling is implicated in the control of cell growth and differentiation
      during CNS development from studies of mouse and chick models, but its action at
      the cellular level has been poorly understand. In this study, we examine the in
      vitro function of Wnt signaling in embryonic neural stem cells, dissociated from
      neurospheres derived from E11.5 mouse telencephalon. Conditioned media containing
      active Wnt-3a proteins are added to the neural stem cells and its effect on
      regeneration of neurospheres and differentiation into neuronal and glial cells
      was examined. Wnt-3a proteins inhibit regeneration of neurospheres, but promote
      differentiation into MAP2-positive neuronal cells. Wnt-3a proteins also increase
      the number of GFAP-positive astrocytes but suppress the number of
      oligodendroglial lineage cells expressing PDGFR or O4. These results indicate
      that Wnt-3a signaling can inhibit the maintenance of neural stem cells, but
      rather promote the differentiation of neural stem cells into several cell
      lineages.

PMID- 14706630
TI  - A yeast one-hybrid system to detect methylation-dependent DNA-protein
      interactions.
AB  - We developed a method for site-selective CpG methylation of the budding yeast
      genome. The method recruits LexA-fused M.SssI DNA methyltransferase to LexA
      operator sequences integrated adjacent to the target site. Microarray analysis of
      methylated DNAs indicated that the tethered enzyme selectively methylates the
      region around the target site. Exploiting this method to methylate bait DNA in
      the one-hybrid system, we demonstrated methylation-dependent DNA binding of
      methyl-CpG binding proteins, MBD1 and Kaiso, in vivo. This methylation-dependent
      one-hybrid system would provide a versatile tool for the search and analysis of
      proteins that recognize methylated DNA to participate in epigenetic regulation.

PMID- 14706631
TI  - Leukaemia inhibitory factor or oncostatin M induction of Swiss 3T3 cells does not
      require mevalonic acid synthesis nor protein isoprenylation to initiate DNA
      replication.
AB  - Leukaemia inhibitory factor (LIF) or Oncostatin M (OSM), both mitogens for Swiss
      mouse 3T3 cells, triggers initiation of DNA synthesis without the requirement for
      mevalonic acid. Thus, Lovastatin (LOV), an inhibitor of the hydroxy
      methylglutaryl CoA (HMGCoA) reductase, does not block LIF or OSM induced DNA
      replication and cell multiplication. In contrast, increasing concentrations of
      LOV from 1 to 60 microM block the mitogenic action of PGF(2alpha) by decreasing
      the number of cells capable of entering S-phase and dividing. This inhibition by
      LOV can be reversed by addition of mevanolactone (MEV), an analogue of mevalonic
      acid. Thus, LIF or OSM triggers initiation of DNA replication independently of
      mevalonic acid synthesis and therefore without the involvement of isoprenylation
      of various signalling proteins.

PMID- 14706632
TI  - Highly specific marker genes for detecting minimal gastric cancer cells in
      cytology negative peritoneal washings.
AB  - Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer
      treatment because advanced gastric cancer often turns out incurable with
      peritoneal metastasis. Molecular detection of minimal cancer cells from
      peritoneal washings may overcome the sensitivity boundary of conventional
      cytology and contribute to the prediction of the disease outcome. To select
      marker candidates out of ten thousands of genes, we performed microarray analyses
      in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40
      candidates selected by the above expression profiling, RT-PCR in 16
      representative peritoneal wash samples was performed to identify genes specific
      to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2,
      TFF1, and TFF2, were then evaluated for their utility as a marker for minimal
      residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five
      genes showed positive results highly specific to incurable cases (91-100%). With
      a high specificity, the combination of these five genes succeeded in identifying
      6 out of 20 (30%) additional patients with all types of early recurrence that
      could not be predicted by the conventional method. The six newly identified
      recurrences included four non-peritoneal ones, showing that RT-PCR using the five
      genes without a real-time quantitative PCR technique contributes to the detection
      of minimal residual disease.

PMID- 14706633
TI  - Antigenicity and receptor-binding ability of recombinant SARS coronavirus spike
      protein.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infectious disease
      associated with a novel coronavirus and causing worldwide outbreaks. SARS
      coronavirus (SARS-CoV) is an enveloped RNA virus, which contains several
      structural proteins. Among these proteins, spike (S) protein is responsible for
      binding to specific cellular receptors and is a major antigenic determinant,
      which induces neutralizing antibody. In order to analyze the antigenicity and
      receptor-binding ability of SARS-CoV S protein, we expressed the S protein in
      Escherichia coli using a pET expression vector. After the isopropyl-beta-D
      thiogalactoside induction, S protein was expressed in the soluble form and
      purified by nickel-affinity chromatography to homogeneity. The amount of S
      protein recovered was 0.2-0.3mg/100ml bacterial culture. The S protein was
      recognized by sera from SARS patients by ELISA and Western blot, which indicated
      that recombinant S protein retained its antigenicity. By biotinylated ELISA and
      Western blot using biotin-labeled S protein as the probe, we identified 130-kDa
      and 140-kDa proteins in Vero cells that might be the cellular receptors
      responsible for SARS-CoV infection. Taken together, these results suggested that
      recombinant S protein exhibited the antigenicity and receptor-binding ability,
      and it could be a good candidate for further developing SARS vaccine and anti
      SARS therapy.

PMID- 14706635
TI  - Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98
      functions.
AB  - Cynaropicrin is a sesquiterpene lactone displaying immunomodulatory effects on
      the production of cytokine and nitric oxide from macrophages/monocytes. In this
      study we have examined inhibitory effect of cynaropicrin on activation of major
      adhesion molecules [CD29 (beta1 integrins), CD43, and CD98] on the cells assessed
      by U937 (promonocytic cells) homotypic aggregation. Cynaropicrin potently blocked
      CD29 (beta1 integrins)- and CD98-induced homotypic aggregation with IC(50) values
      of 3.46 and 2.98 microM, respectively, without displaying cytotoxicity.
      Similarly, flow cytometric analysis exhibited that cynaropicrin down-regulated
      strikingly surface level of CD29 and CD147, a functional regulator of CD98, but
      not CD43. More importantly, cynaropicrin inhibition was linked to blockade of
      extracellular signal-related kinase (ERK) activation and distinct from other
      enzyme inhibitors including rottlerin, propranolol, forskolin, and chloroquine,
      but not cytochalasin B. Therefore, our finding is the first demonstration that
      cynaropicrin may be a potent functional regulator of CD29 and CD98 via
      interrupting ERK activation which may be linked to cytoskeleton rearrangement,
      suggesting further application to CD29- and CD98-mediated diseases such as virus
      induced chronic inflammation, and invasion, migration, and metastasis of
      leukocyte cancer cells.

PMID- 14706634
TI  - (-)-3,5-Dicaffeoyl-muco-quinic acid isolated from Aster scaber contributes to the
      differentiation of PC12 cells: through tyrosine kinase cascade signaling.
AB  - Aster scaber T. (Asteraceae) has been used in traditional Korean and Chinese
      medicine to treat bruises, snakebites, headaches, and dizziness. (-)-3,5
      Dicaffeoyl-muco-quinic acid (DQ) isolated from A. scaber induced neurite
      outgrowth in PC12 cells. It has been reported that the activation of the
      extracellular signal regulated kinase 1/2 (Erk 1/2) and phosphoinositide 3 (PI3)
      kinase plays a crucial role in the NGF-induced differentiation of PC12 cells.
      This study showed that the effect of DQ on neurite outgrowth is mediated via the
      Erk 1/2 and PI3 kinase-dependent pathways like NGF. Furthermore, DQ stimulated
      the phosphorylation of Trk A. Overall, DQ elicited the differentiation of PC12
      cells through Trk A phosphorylation followed by Erk 1/2 and PI3 kinase
      activation.

PMID- 14706636
TI  - Human extravillous trophoblasts express laeverin, a novel protein that belongs to
      membrane-bound gluzincin metallopeptidases.
AB  - Human extravillous trophoblasts (EVTs) invade the maternal decidua. To identify
      the molecules involved in EVT invasion, we raised a murine monoclonal antibody
      (CHL2) that reacts with human EVTs. The molecular mass of CHL2 antigen purified
      from placental tissues was 160 kDa. Although the N-terminal partial amino acid
      sequence and one internal sequence are still unreported, the other three internal
      sequences matched those deduced from the coding region of the estimated sequence
      tag (1672 bp, AK075131). Based on this information, the full-length of the coding
      cDNA sequence of CHL2 antigen (2970 bp), which has not been reported elsewhere,
      was determined by 5' RACE. This novel protein, named laeverin, has a peptidase M1
      motif containing a zinc-binding active site. It also has a transmembrane domain
      near the N-terminus. Its amino acid sequence is homologous with aminopeptidase N.
      These data indicate that human EVTs express laeverin, a novel protein belonging
      to gluzincin metallopeptidases.

PMID- 14706637
TI  - Human zinc finger protein 161, a novel transcriptional activator of the dopamine
      transporter.
AB  - The dopamine transporter (DAT) terminates dopaminergic neurotransmission via
      reuptake of released dopamine into presynaptic neurons. We have cloned 2.5 kb of
      the regulatory region upstream of human DAT (hDAT) and constructed a series of
      deletion mutants to test promoter activity. A comparison of promoter activity
      between non-neural and neuronal cell lines reveals an interesting difference in
      pattern. In the PC12 cell line, activity of the proximal promoter is strongly
      silenced by one or more unidentified elements spanning positions -395 to -2465 of
      the hDAT gene. Our studies focus on identifying and characterizing the activating
      factor for hDAT transcription in the sequence between -2511 and -2492 (5(')-CTA
      CCT GCA CAG TTC ACG GA-3('), termed HY1). In this investigation, we cloned the
      zinc finger protein 161 (ZFP161) gene as a HY1-binding factor, using the yeast
      one-hybrid screen. Recombinant ZFP161 was produced to evaluate the DNA-binding
      properties of the protein. The ability of ZFP161 to directly bind HY1 was
      examined in an electrophoretic mobility shift assay. RT-PCR analyses revealed
      that transfection of ZFP161 induced hDAT mRNA expression in HEK293 cells. We
      additionally confirmed the expression and localization of the DAT protein, using
      a specific antibody. Both the HY1 sequence and the downstream region were
      necessary for activation of the hDAT promoter by ZFP161. This finding suggests
      that the site of cofactor interaction with ZFP161 may exist downstream of HY1.

PMID- 14706638
TI  - Anisomycin superinduces annexin V mRNA expression through the ERK1/2 but not the
      p38 MAP kinase pathway.
AB  - Annexin V is a Ca(2+)-dependent phospholipid-binding protein belonging to the
      annexin family whose regulation is currently not well understood. In this study,
      we utilized anisomycin, a protein synthesis inhibitor that activates MAP kinases
      (MAPKs), to examine the role of MAPKs in annexin V expression in the MCAS ovarian
      carcinoma cell line. A one-step real-time TaqMan-based reverse transcriptase-PCR
      method was developed to quantify annexin V mRNA expression. We found that annexin
      V was induced 13.3-fold by anisomycin and that this superinduction was attenuated
      by pretreatment with the MEK inhibitors, U0126 and PD98059, but not with the p38
      MAPK inhibitor, SB203580. In addition, immunoblotting showed that anisomycin
      stimulated the phosphorylation of ERK1/2 as well as p38 MAPK and that the
      phosphorylations were blocked by the three kinase inhibitors. Taken together,
      these results suggest that anisomycin superinduces annexin V mRNA expression
      through the ERK1/2 MAPK pathway, but not through the p38 MAPK pathway.

PMID- 14706639
TI  - Modification of glycolysis affects cell sensitivity to apoptosis induced by
      oxidative stress and mediated by mitochondria.
AB  - The effect of alteration of the glycolytic pathway on cell damage induced by
      oxidative stress was investigated with dihydrofolate reductase-deficient Chinese
      hamster ovary (CHO) cells that either overexpress cytosolic glycerol-3-phosphate
      dehydrogenase (CHO/cGPDH cells) or are depleted of the A subunit of lactate
      dehydrogenase as a result of anti-sense RNA expression (CHO/anti-LDH cells). The
      extent of oxidative phosphorylation in CHO/anti-LDH and CHO/cGPDH cells was
      increased and decreased, respectively, relative to that in parental CHO cells, as
      revealed by measurement of the intracellular content of ATP, the rate of cellular
      O(2) consumption, the mitochondrial membrane potential (DeltaPsi(m)), and the
      generation of reactive oxygen species. The sensitivity of these cell lines to
      cell death induced by the exogenous oxidant tert-butyl hydroperoxide decreased
      according to the rank order CHO/anti-LDH>CHO>CHO/cGPDH. Exogenous pyruvate
      markedly increased the sensitivity of CHO/cGPDH cells to oxidant-induced death.
      The differences among the three cell lines in susceptibility to oxidant-induced
      death were reflected in the proportion of oxidant-treated cells with a subdiploid
      DNA content, with a collapsed DeltaPsi(m), and with cytochrome c in the cytosol,
      indicating that death was mediated by apoptosis. These results demonstrate that
      the influx of respiratory substrate into mitochondria is an important determinant
      of cell sensitivity to oxidant-induced apoptosis.

PMID- 14706640
TI  - Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a
      novel myosin II inhibitor.
AB  - Blebbistatin is a novel 1-phenyl-2-pyrrolidinone derivative capable of inhibiting
      non-muscle myosin II activity with a high degree of specificity. We examined the
      effects of blebbistatin on pancreatic adenocarcinoma cellular migration,
      invasion, adhesion, and spreading. Blebbistatin dose-dependently inhibited
      cellular migration and invasiveness, quantified by modified Boyden chamber assay.
      Matrix metalloproteinase 2 and 9 activities were unaffected by blebbistatin and
      cellular proliferation was inhibited only by concentrations of blebbistatin
      exceeding those required to inhibit myosin II activity and to interfere with
      migration and invasion. While blebbistatin treatment did not affect cell adhesion
      to the extracellular matrix component fibronectin, it markedly impaired cell
      spreading on this substrate. Cell surface expression of the archetypal
      fibronectin receptor (alpha(5)beta(1) integrin) was unaffected by blebbistatin.
      Our observations illustrate the critical role of non-muscle myosin II in
      pancreatic adenocarcinoma cellular invasiveness and extracellular matrix
      interaction and suggest that therapeutic strategies targeting myosin II warrant
      further investigation.

PMID- 14706641
TI  - Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger
      regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and
      protein kinase B.
AB  - Renal tubular citrate transport is accomplished by electrogenic Na(+) coupled
      dicarboxylate transporter NaDC-1, a carrier subjected to regulation by acidosis.
      Trafficking of the Na(+)/H(+) exchanger NHE3 is controlled by NHE regulating
      factors NHERF-1 and NHERF-2 and the serum and glucocorticoid inducible kinase
      SGK1. To test for a possible involvement in NaDC-1 regulation, mRNA encoding NaDC
      1 was injected into Xenopus oocytes with or without cRNA encoding NHERF-1, NHERF
      2, SGK1, SGK2, SGK3, and/or the constitutively active form of the related protein
      kinase B ((T308,S473D)PKB). Succinate induced inward currents (I(succ)) were
      taken as a measure of transport rate. Coexpression of neither NHERF-1 nor NHERF-2
      in NaDC-1 expressing oocytes significantly altered I(succ). On the other hand,
      coexpression of SGK1, SGK3, and (T308,S473D)PKB stimulated I(succ), an effect
      further stimulated by additional coexpression of NHERF-2 but not of NHERF-1. The
      action of the kinases and NHERF-2 may link urinary citrate excretion to proximal
      tubular H(+) secretion.

PMID- 14706642
TI  - In vitro evolution of RNA aptamers recognizing carcinogenic aromatic amines.
AB  - The modification of cellular DNA by environmental substances is thought to be a
      crucial event in chemical induced carcinogenesis. Among the environmental
      carcinogens, aromatic amines are known for the fact that they can induce several
      types of cancers through the formation of so-called DNA adducts. We took
      advantage of the potential of the SELEX method to select for highly specific RNA
      ligands that recognize specific genotoxic aromatic amines. The aromatic amine
      4,4'-methylenedianiline (MDA) was used as a target. Following in vitro selection,
      we obtained specific MDA-binding RNA molecules based on an affinity
      chromatography assay. These results open the possibility of using the SELEX
      technique to generate RNA molecules as diagnostic tools for the detection of DNA
      damaging compounds and ultimately DNA adducts.

PMID- 14706643
TI  - An autocrine function of nerve growth factor for cell cycle regulation of
      vascular endothelial cells.
AB  - Nerve growth factor (NGF) regulates maintenance, survival, and function of not
      only neuronal cells but also various kinds of non-neuronal cells. Here we clearly
      demonstrated that mouse aortic endothelial cells (AEC) produced bioactive NGF,
      and the production was enhanced by a proinflammatory cytokine, interleukin (IL)
      1beta. AEC expressed both high affinity (TrkA) and low affinity (p75(NGFR))
      receptors for NGF. Exogenously added NGF induced rapid phosphorylation of TrkA
      tyrosine kinase. Addition of anti-NGF neutralizing antibody resulted in an
      increase in the proportion of AEC in S and G(2)/M phases and in a hypodiploid
      range. Since the vascular endothelium plays a pivotal role in inflammatory
      conditions, these results strongly suggest that NGF, whose production is enhanced
      at the affected site, may contribute to maintenance, survival, and function of
      vascular endothelial cells by autocrine and/or paracrine mechanisms.

PMID- 14706644
TI  - Study of drug effects of calcium channel blockers on retinal degeneration of rd
      mouse.
AB  - In the present study, we studied drug effects of Ca(2+) antagonists on the
      retinal degeneration of rd mouse to evaluate their efficacy. Several kinds of
      Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine or nifedipine were
      administrated intraperitoneally and thereafter retinal morphology and functions
      were analyzed. In addition, we performed DNA microarray analysis both in
      nilvadipine treated and control retinas to understand their drug effects at
      molecular levels. We found that nilvadipine caused significant preservation of
      retinal thickness in rd mouse during the initial stage of the retinal
      degeneration, and nicardipine showed also significant but lesser preservation
      than nilvadipine. However, we recognized no preservation effects of diltiazem and
      nifedipine. In the total 3774 genes, the expressions of 27 genes were altered
      upon administration of nilvadipine, including several genes related to the
      apoptotic pathway, neuro-survival factor, Ca(2+) metabolisms, and other
      mechanisms. It is suggested that some types of Ca(2+) channel blockers, such as
      nilvadipine and nicardipine, are able to preserve photoreceptor cells in rd mouse
      and can potentially be used to treat some RP patients.

PMID- 14706645
TI  - Targeted degradation of beta-catenin by chimeric F-box fusion proteins.
AB  - Adenomatous polyposis coli (APC) tumor suppressor protein, together with Axin and
      glycogen synthase kinase 3beta (GSK-3beta), forms a Wnt-regulated signaling
      complex that mediates phosphorylation-dependent degradation of cytoplasmic beta
      catenin by ubiquitin-dependent proteolysis. Degradation of phosphorylated beta
      catenin is initiated by interaction through the WD40-repeat of a F-box protein
      beta-TrCP, a component of SCF ubiquitin ligase complex. Mutations in APC, Axin,
      and beta-catenin that prevent down-regulation of cytoplasmic beta-catenin are
      found in various types of cancers. In the search for efficient treatment and
      prevention of malignancies associated with increased levels of cytoplasmic beta
      catenin, we created chimeric F-box fusion proteins by replacing the WD40-repeat
      of beta-TrCP with the beta-catenin-binding domains of Tcf4 and E-cadherin.
      Expression of chimeric F-box fusion proteins successfully promotes degradation of
      beta-catenin independently of GSK-3beta-mediated phosphorylation. More
      importantly, this degradation does not require intact APC protein (pAPC).

PMID- 14706646
TI  - Impact of embryonic expression of enhanced green fluorescent protein on early
      mouse development.
AB  - The impact of embryonic enhanced green fluorescent protein (EGFP)-expression on
      development is not clear. In this study, we comprehensively assessed EGFP
      expression pattern and its effect on early mouse development, following
      pronuclear-microinjection of the EGFP-transgene, containing chicken-beta-actin
      promoter and cytomegalovirus enhancer. Preimplantation embryos exhibited
      differential EGFP-expression patterns. While blastocyst development of non
      expressing embryos was 77.3+/-1.8%, that of expressing embryos was only 43.9+/
      1.6% (P<0.0001). Developmental competence of embryos negatively correlated (r=
      0.99) with the levels of EGFP-expression. Faint-, moderate-, and intense
      expressing embryos developed to 83.1+/-5.3%, 50+/-5%, and 9.5+/-3.9% blastocysts,
      respectively (P<0.002). Interestingly, blastocysts expressing faint-moderate
      levels of EGFP were developmentally competent through the post-implantation
      period and delivered viable transgenic 'green' mice, following embryo transfer.
      These results indicate that hyper-expression of EGFP affects preimplantation
      development and faint-moderate level of its expression is compatible with normal
      embryogenesis in the mouse.

PMID- 14706647
TI  - Involvement of telomere dysfunction in the induction of genomic instability by
      radiation in scid mouse cells.
AB  - To determine the effects of a defect in NHEJ on the induction of genomic
      instability by radiation, we investigated X-ray-induced delayed chromosomal
      aberrations such as dicentrics and fragments in scid mouse cells. We found that
      radiosensitive scid mouse cells are more susceptible than wild-type mouse cells
      to the induction of delayed chromosomal aberrations when the cells are exposed to
      an equivalent survival dose of X-rays. Telomere FISH analysis revealed that
      radiation enhances the induction of telomeric fusions where telomeric sequences
      remain at the fused position (tel+ end-fusions), suggesting that radiation
      induces telomere dysfunction. Moreover, formation of the tel+ end-fusions was
      found to be enhanced in scid mouse cells, suggesting that DNA-dependent protein
      kinase catalytic subunit (DNA-PKcs) plays a role in telomeric stabilization.
      Thus, the present study suggests that a cause of genomic instability is telomere
      dysfunction induced by radiation and that a defect in DNA-PKcs enhances the
      telomeric destabilization.

PMID- 14706648
TI  - Direct evidence for cyanide-insensitive quinol oxidase (alternative oxidase) in
      apicomplexan parasite Cryptosporidium parvum: phylogenetic and therapeutic
      implications.
AB  - Cryptosporidium parvum is a parasitic protozoan that causes the diarrheal disease
      cryptosporidiosis, for which no satisfactory chemotherapy is currently available.
      Although the presence of mitochondria in this parasite has been suggested, its
      respiratory system is poorly understood due to difficulties in performing
      biochemical analyses. In order to better understand the respiratory chain of C.
      parvum, we surveyed its genomic DNA database in GenBank and identified a partial
      sequence encoding cyanide-insensitive alternative oxidase (AOX). Based on this
      sequence, we cloned C. parvum AOX (CpAOX) cDNA from the phylum apicomplexa for
      the first time. The deduced amino acid sequence (335 a.a.) of CpAOX contains
      diiron coordination motifs (-E-, -EXXH-) that are conserved among AOXs.
      Phylogenetic analysis suggested that CpAOX is a mitochondrial-type AOX, possibly
      derived from mitochondrial endosymbiont gene transfer. The recombinant enzyme
      expressed in Escherichia coli showed quinol oxidase activity. This activity was
      insensitive to cyanide and highly sensitive to ascofuranone, a specific inhibitor
      of trypanosome AOX.

PMID- 14706649
TI  - A trans-Golgi network retention signal YQRL fused to ricin A chain significantly
      enhances its cytotoxicity.
AB  - Ricin enters the cells by receptor-mediated endocytosis, followed by
      translocation across the membranes of intracellular organelles. A trans-Golgi
      retention peptide signal YQRL was fused to the C-terminus of ricin A chain (RTA)
      by polymerase chain reaction. The recombinant RTA and RTA-YQRL were expressed in
      Escherichia coli using plasmid pKK223.3 under the control of a tac promoter. The
      recombinant proteins were purified by affinity chromatography on a Blue-Sepharose
      6B column. The cytotoxicities of RTA and the fusion toxin RTA-YQRL were measured
      by the MTT assay in HeLa, SKOV-3, and WISH cells following fluid-phase
      endocytosis. The rRTA-YQRL was 2-, 10-, and 40-fold more cytotoxic than rRTA
      itself in the three cell lines, respectively. The results indicate that addition
      of a TGN retention signal YQRL to the C-terminus of RTA can markedly increase its
      cytotoxicity, suggesting TGN may play an important role in the intracellular
      routing and translocation of RTA.

PMID- 14706650
TI  - Identification of novel initiation sites for human DNA replication around ARSH1,
      a previously characterized yeast replicator.
AB  - Replication of mammalian chromosomes depends on the activation of a large number
      of origins of DNA replication distributed along the chromosomes. We have focused
      our attention on a human DNA region, named ARSH1, localized to chromosome 2, that
      had been previously shown to act as an episomal origin in the yeast Saccharomyces
      cerevisiae. In the present study we have used a nascent strand DNA abundance
      assay to map initiation sites for DNA replication in in vivo human chromosomes
      around a 5 kb region encompassing ARSH1. This analysis applied to a 1-1.4 kb
      nascent DNA strand fraction isolated from normal skin fibroblasts revealed the
      presence of two major initiations sites surrounding the ARSH1 region. With an
      equivalent DNA fraction obtained from HeLa cells, in addition to these sites, a
      broad initiation profile was observed which included the ARSH1 region. This DNA
      region however was not sufficient to support episomal replication of an ARSH1
      containing plasmid transfected into HeLa cells.

PMID- 14706651
TI  - Structural studies of oligonucleotides containing G-quadruplex motifs using AFM.
AB  - G-quadruplex DNAs are cyclic arrays of four guanine bases binding by Hoogsteen
      hydrogen bonds, found in the telomeric regions of chromosomes and in
      transcriptional regulatory regions of several important oncogenes. Here, we used
      high resolution atomic force microscopy (AFM) to observe a specific guanine (G)
      tetrad mediated complex formation of oligonucleotides containing a G-quadruplex
      motifs (G-ODN) combined with a palindromic sequence under physiological
      extracellular conditions. These oligonucleotides have been investigated in
      correlation to their immunostimulatory effects. We observed structural dependence
      on ion concentration and G-ODN concentration, where high concentration self
      assembled DNA networks were formed.

PMID- 14706652
TI  - Topoisomerase I dissociates human immunodeficiency virus type 1 reverse
      transcriptase from genomic RNAs.
AB  - Both HIV-1 reverse transcriptase (RT) and topoisomerase I bind to structural RNAs
      and they cooperate to synthesize cDNA during the replication of HIV-1. In this
      study, we find that human topoisomerase I exclusively dissociated HIV-1 reverse
      transcriptase, which strongly binds to structural RNAs. Meanwhile, topoisomerase
      I did not dissociate either HIV-1 nucleocapsid proteins or murine leukemia virus
      RT which was bound to RNA. We propose that human topoisomerase I may regulate the
      binding of RT to RNAs and play a pivotal role in HIV-1 replication.

PMID- 14706653
TI  - Genetic polymorphims in promoter region of osteopontin gene may be a marker
      reflecting hepatitis activity in chronic hepatitis C patients.
AB  - BACKGROUND AND AIMS: Osteopontin, an extracellular matrix protein with RGD motif,
      is shown to be a cytokine essential for Th1 immune response initiation. Genetic
      polymorphisms in the osteopontin gene (OPN) determine the magnitude of immunity
      against rickettsial infection in mice. Similar polymorphisms, if present also in
      human beings, might affect hepatitis activity in those infected with HCV.
      METHODS: Blood was collected from 176 patients with chronic hepatitis C. SNPs in
      the promoter region of OPN were analyzed in 20 patients by direct sequencing of
      DNA fragments amplified by PCR and in 156 patients by Invader assay. Ninety-five
      patients compatible to evaluation criteria were classified into three groups
      depending on maximal serum ALT levels during the observation periods at least for
      2 years as follows; lower than 30IU/L (low-activity group), between 30 and 80IU/L
      with no hepatoprotective treatment (medium-activity group), and higher than
      80IU/L irrespective of hepatoprotective treatment (high-activity group). RESULTS:
      There were 16, 19, and 60 patients in the low-, medium-, and high-activity
      groups, respectively. Four SNPs (nt -155, -443, -616, and -1748) were detected in
      the promoter region of OPN. Among them, the SNP at nt -443 (C or T) was a novel
      one and showed an association with hepatitis activity in our patients: T/T
      homozygosity was found in 2 (13%), 8 (42%), and 25 (44%), and C/T heterozygosity
      in 12 (75%), 8 (42%), and 23 (40%), in the low-, medium-, and high-activity
      groups, respectively. The other 3 SNPs already known showed linkage
      disequilibrium with D(') and r(2) greater than 0.937 to each other without
      correlation to disease activity. CONCLUSIONS: OPN promoter region SNP at nt -433
      may be a useful marker reflecting hepatitis activity in chronic hepatitis C
      patients.

PMID- 14706654
TI  - FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain,
      promotes neurite outgrowth.
AB  - The mature peripheral nervous system has the ability to survive and to regenerate
      its axons following axonal injury. After nerve injury, the distal axonal and
      myelin segment undergoes dissolution and absorption by the surrounding cellular
      environment, a process called Wallerian degeneration. Using cDNA microarrays, we
      isolated FLRT3 as one of the up-regulated genes expressed in the distal segment
      of the sciatic nerve 7 days after transection relative to those of the intact
      sciatic nerve. FLRT3 is a putative type I transmembrane protein containing 10
      leucine-rich repeats, a fibronectin type III domain, and an intracellular tail.
      The neurons plated on CHO cells expressing FLRT3 extended significantly longer
      neurites than those plated on wild-type CHO cells, demonstrating that FLRT3
      promotes neurite outgrowth. FLRT3 mRNA was especially abundant in the basal
      ganglia, the granular layer of cerebellum, and the hippocampus, except the CA1
      region in the adult rat brain. Thus, FLRT3 may contribute to regeneration
      following axonal injury.

PMID- 14706655
TI  - A novel smoothelin-like, actin-binding protein required for choroidal fissure
      closure in zebrafish.
AB  - A gene expressed in the choroidal fissure of the zebrafish eye was isolated. This
      gene, designated #61, contained significant homology with the previously reported
      actin-binding protein smoothelin. During zebrafish embryogenesis, #61 expression
      was first detected in the lateral mesoderm of the mid-trunk region, and then
      strong expression was observed in the choroid fissure of the eye and in a part of
      the brain at 30 hpf. Abrogation of #61 activity by an antisense morpholino
      oligonucleotide resulted in the failure of closure of the choroid fissure at 30
      hpf. In addition, hemorrhage was observed at the caudal side of the eye. Detailed
      analysis indicated that leakage of blood may have arisen from the hyaloid vessels
      and the primordial midbrain channels. On the other hand, retinal differentiation
      and optic nerve formation seemed normal. Taken together, our data suggest that
      gene #61 may play a role in the formation of hyaloid vessels and subsequent
      choroid fissure closure.

PMID- 14706656
TI  - The carbohydrate-binding domain of Lafora disease protein targets Lafora
      polyglucosan bodies.
AB  - Lafora's disease (LD) is an autosomal recessive and fatal form of epilepsy with
      onset in late childhood or adolescence. One of the characteristic features of LD
      pathology is the presence of periodic acid-Schiff (PAS) positive Lafora inclusion
      bodies. Lafora bodies are present primarily in neurons, but they have also been
      found in other organs. Histochemical and biochemical studies have indicated that
      Lafora bodies are composed mainly of polysaccharides. The LD gene, EPM2A, encodes
      a 331 amino acid long protein named laforin that contains an N-terminal
      carbohydrate-binding domain (CBD) and a C-terminal dual-specificity phosphatase
      domain (DSPD). Here we demonstrate that the CBD of laforin targets the protein to
      Lafora inclusion bodies and this property could be evolutionarily conserved. We
      also tested in vitro the effects of five LD missense mutations on laforin's
      affinity to Lafora body. While the missense mutant W32G failed to bind to
      purified Lafora body, four other mutants (S25P, E28L, F88L, and R108C) did not
      show any effect on the binding affinity. Based on these observations we propose
      the existence of a laforin-mediated glycogen metabolic pathway regulating the
      disposal of pathogenic polyglucosan inclusions. This is the first report
      demonstrating a direct association between the LD gene product and the disease
      defining storage product, the Lafora bodies.

PMID- 14706657
TI  - A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is
      useful for cell therapy to repair damaged liver.
AB  - We previously reported a new in vivo model named as "GFP/CCl(4) model" for
      monitoring the transdifferentiation of green fluorescent protein (GFP) positive
      bone marrow cell (BMC) into albumin-positive hepatocyte under the specific
      "niche" made by CCl(4) induced persistent liver damage, but the subpopulation
      which BMCs transdifferentiate into hepatocytes remains unknown. Here we developed
      a new monoclonal antibody, anti-Liv8, using mouse E 11.5 fetal liver as an
      antigen. Anti-Liv8 recognized both hematopoietic progenitor cells in fetal liver
      at E 11.5 and CD45-positive hematopoietic cells in adult bone marrow. We
      separated Liv8-positive and Liv8-negative cells and then transplanted these cells
      into a continuous liver damaged model. At 4 weeks after BMC transplantation, more
      efficient repopulation and transdifferentiation of BMC into hepatocytes were seen
      with Liv8-negative cells. These findings suggest that the subpopulation of Liv8
      negative cells includes useful cells to perform cell therapy on repair damaged
      liver.

PMID- 14706658
TI  - Obesity-associated hypoventilation in hospitalized patients: prevalence, effects,
      and outcome.
AB  - BACKGROUND: Severe obesity is associated with hypoventilation, a disorder that
      may adversely affect morbidity and mortality. We sought to determine the
      prevalence and effects of obesity-associated hypoventilation in hospitalized
      patients. METHODS: Consecutive admissions to internal medicine services were
      screened over a 6-month period. In all eligible subjects with severe obesity
      (body mass index > or =35 kg/m2), we administered a sleep questionnaire, and
      performed neuropsychological, arterial blood gas, and pulmonary function testing.
      Hospital course and mortality at 18 months was also determined. RESULTS: Of 4,332
      admissions, 6% (n = 277) of patients were severely obese, of whom 150 were
      enrolled, 75 refused to participate, and 52 met the exclusion criteria.
      Hypoventilation (mean [+/- SD] arterial partial pressure of carbon dioxide
      [PaCO2], 52 +/- 7 mm Hg) was present in 31% (n = 47) of subjects who did not have
      other reasons for hypercapnia. Decreased objective attention/concentration and
      increased subjective sleepiness were present in patients with obesity-associated
      hypoventilation compared with in severely obese hospitalized patients without
      hypoventilation (simple obesity group; mean PaCO2, 37 +/- 6 mm Hg). There were
      higher rates of intensive care (P = 0.08), long-term care at discharge (P =
      0.01), and mechanical ventilation (P = 0.01) among subjects with obesity
      associated hypoventilation. Therapy for hypoventilation at discharge was
      initiated in only 6 (13%) of the patients with obesity-associated
      hypoventilation. At 18 months following hospital discharge, mortality was 23% in
      the obesity-associated hypoventilation group as compared with 9% in the simple
      obesity group (hazard ratio = 4.0; 95% confidence interval: 1.5 to 10.4].
      CONCLUSION: Hypoventilation frequently complicates severe obesity among
      hospitalized adults and is associated with excess morbidity and mortality.

PMID- 14706659
TI  - Aortic stenosis: an underestimated risk factor for perioperative complications in
      patients undergoing noncardiac surgery.
AB  - PURPOSE: To determine the incidence of perioperative events in patients with
      aortic stenosis undergoing noncardiac surgery. METHODS: We studied 108 patients
      with moderate (mean gradient, 25 to 49 mm Hg) or severe (mean gradient, > or =50
      mm Hg) aortic stenosis and 216 controls who underwent noncardiac surgery between
      1991 and 2000 at Erasmus Medical Center. Controls were selected based on calendar
      year and type of surgery. Details of clinical risk factors, type of surgery, and
      perioperative management were retrieved from medical records. The main outcome
      measure was the composite of perioperative mortality and nonfatal myocardial
      infarction. RESULTS: There was a significantly higher incidence of the composite
      endpoint in patients with aortic stenosis than in patients without aortic
      stenosis (14% [15/108] vs. 2% [4/216], P <0.001). This rate of perioperative
      complications was also substantially higher in patients with severe aortic
      stenosis compared with patients with moderate aortic stenosis (31% [5/16] vs. 11%
      [10/92], P = 0.04). After adjusting for cardiac risk factors, aortic stenosis
      remained a strong predictor of the composite endpoint (odds ratio = 5.2; 95%
      confidence interval: 1.6 to 17.0). CONCLUSION: Aortic stenosis is a risk factor
      for perioperative mortality and nonfatal myocardial infarction, and the severity
      of aortic stenosis is highly predictive of these complications.

PMID- 14706660
TI  - Prevalence of idiopathic hypertrophic cardiomyopathy in China: a population-based
      echocardiographic analysis of 8080 adults.
AB  - PURPOSE: To determine the prevalence of hypertrophic cardiomyopathy in China.
      METHODS: This epidemiologic investigation was performed in 8080 adults from nine
      communities across nine provinces in China from October 2001 to February 2002,
      using a multistage, random sample design. Hypertrophic cardiomyopathy was defined
      as nondilated ventricular hypertrophy, documented by echocardiography, that was
      not caused by any known cardiac or systemic disease. RESULTS: Of the 4064 men and
      4016 women who were screened, 13 (0.16%; 9 men and 4 women) had definite
      echocardiographic evidence for hypertrophic cardiomyopathy. The age- and sex
      adjusted prevalence was about 80 per 100,000 adults. CONCLUSION: Hypertrophic
      cardiomyopathy is not rare in China. Based on the estimated prevalence, there are
      at least 1 million cases in China.

PMID- 14706661
TI  - Clinical characteristics of and long-term outcome in Chinese patients with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Data on the phenotypical pattern and natural history of hypertrophic
      cardiomyopathy in Chinese patients are very limited. The purpose of this study
      was to describe the clinical characteristics of and long-term outcome in Chinese
      patients with hypertrophic cardiomyopathy. METHODS: We evaluated 118 Chinese
      patients (62 male) who were diagnosed with hypertrophic cardiomyopathy at Queen
      Mary Hospital from 1973 to 2002. Diagnosis was based on the demonstration of left
      ventricular hypertrophy (wall thickness > or =15 mm during diastole), either in a
      specific region or with diffuse distribution, using echocardiography or magnetic
      resonance imaging. Clinical predictors of major cardiovascular events related to
      hypertrophic cardiomyopathy (cardiovascular death, potentially fatal cardiac
      arrhythmia, and refractory heart failure requiring cardiac transplantation or
      percutaneous alcohol septal ablation) were evaluated with univariate and
      multivariate Cox proportional hazards regression models. RESULTS: The mean (+/-
      SD) age at presentation was 54 +/- 18 years. During a mean follow-up of 5.8 +/-
      4.3 years (range, 1 to 29 years) from presentation, major cardiovascular events
      related to hypertrophic cardiomyopathy occurred in 19 patients (16%), including 9
      deaths. Annual cardiovascular mortality was 1.6%. Fifty-five patients (47%) had
      one or more cardiovascular complications related to hypertrophic cardiomyopathy,
      of which atrial fibrillation was the most common (35%, n = 41). The most common
      type of hypertrophic cardiomyopathy was the apical variant (41%, n = 49). In
      multivariate analysis, female sex was the only independent predictor of major
      cardiovascular events related to hypertrophic cardiomyopathy (hazard ratio =
      5.86; 95% confidence interval: 1.77 to 7.21; P = 0.007). CONCLUSION: Hypertrophic
      cardiomyopathy in Chinese patients is characterized by late onset of
      presentation, a high incidence of the apical form of the condition, and adverse
      clinical outcome in female patients, which suggest a different phenotypical
      pattern than in white patients.

PMID- 14706662
TI  - Circadian distribution of acute myocardial infarction by anatomic location and
      coronary artery involvement.
AB  - PURPOSE: Acute myocardial infarction follows a circadian pattern, with a morning
      peak ascribed to sympathetic activation. However, about 20% of myocardial
      infarctions occur between midnight and 6 AM; these events may have different
      characteristics. METHODS: We studied 1571 patients with acute myocardial
      infarction (866 anterior and 705 inferior myocardial infarctions) who were
      admitted to our coronary care units from January 1997 to February 2001. We noted
      the time of the infarction, its anatomic location, and the involved coronary
      arteries. RESULTS: Inferior myocardial infarctions were more frequent during the
      night (midnight to 6 AM) than during other periods of the day (n = 238, 34% of
      all inferior infarctions, P <0.01). When coronary angiography was performed (795
      patients), 92% (127/138) of inferior infarctions were due to right coronary
      artery occlusion, whereas only 54% (130/242) of the remaining inferior
      infarctions involved that artery. CONCLUSION: Inferior myocardial infarctions
      occur disproportionately at night, usually due to right coronary artery
      occlusion. This suggests that a protective role for sleep may be limited to left
      coronary artery-related events.

PMID- 14706664
TI  - Calcium channel blockers: an update.
AB  - This paper reviews the current literature pertaining to calcium channel blockers,
      including their classification, properties, and therapeutic indications, in light
      of several recent trials that have addressed their safety. Calcium channel
      blockers are a structurally and functionally heterogeneous group of medications
      that are used widely to control blood pressure and manage symptoms of angina.
      They are classified as dihydropyridines or nondihydropyridines. As a class, they
      are well tolerated and are associated with few side effects. The question of
      whether they may precipitate cardiovascular events has been largely settled by
      recent trials, such as the Antihypertensive and Lipid-Lowering Treatment to
      Prevent Heart Attack Trial (ALLHAT), the International Verapamil Slow
      Release/Trandolapril Study (INVEST), and the Controlled Onset Verapamil
      Investigation of Cardiovascular Endpoints (CONVINCE) study, in which no such
      association was found. Even so, the use of these agents has been linked with an
      increased risk of heart failure. Thus, long-acting calcium channel blockers may
      be safely used in the management of hypertension and angina. However, as a class,
      they are not as protective as other antihypertensive agents against heart
      failure.

PMID- 14706663
TI  - Use of erythropoietin in cancer patients: assessment of oncologists' practice
      patterns in the United States and other countries.
AB  - PURPOSE: To assess physician use of erythropoietin in cancer patients before
      publication of the American Society of Clinical Oncology/American Society of
      Hematology guidelines. METHODS: Questionnaires about erythropoietin use in
      practice and 12 hypothetical clinical scenarios involving patients with cancer
      were mailed to 2000 oncologists/hematologists in the United States and 19 other
      countries. Response rates were 30% in the United States and 25% internationally.
      Data on erythropoietin use for ovarian cancer were obtained from one clinical
      trial. Multivariate regression models assessed predictors of erythropoietin
      prescription. RESULTS: Most physicians selected a hemoglobin level < or =10 g/dL
      as an upper threshold for erythropoietin use (36% to 51% of U.S. physicians and
      21% to 32% of foreign physicians). Frequent erythropoietin use (defined as use in
      at least 10% of cancer patients) was higher in the United States than elsewhere
      (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5 to 13.4).
      Among U.S. physicians, those who said they used erythropoietin frequently were
      more likely to be in fee-for-service than managed care settings (OR = 2.2; 95%
      CI: 1.3 to 3.7). Those who reported never using erythropoietin practiced in
      countries that had lower annual per capita health care expenditures, lower
      proportions of privately funded health care, and a national health service (P
      <0.05 for all comparisons). Of 235 ovarian cancer patients who received
      topotecan, 38% (45/118) of U.S. patients and 2% (2/117) of European patients who
      developed grade 1 anemia (hemoglobin level between 10 and 12 g/dL) were treated
      with erythropoietin (P <0.01). CONCLUSION: Financial considerations and a
      hemoglobin level <10 g/dL appear to influence erythropoietin use in the United
      States, whereas financial considerations alone determine erythropoietin use
      abroad.

PMID- 14706665
TI  - Are calcium antagonists beneficial in diabetic patients with hypertension?
AB  - PURPOSE: We analyzed the available data to assess the effects of calcium
      antagonists in hypertensive patients with diabetes mellitus. METHODS: We
      performed a MEDLINE search of English-language articles published until April
      2003, using the terms diabetes mellitus, hypertension or blood pressure, and
      therapy. Pertinent articles cited in the identified papers were also reviewed. We
      included prospective randomized studies of more than 12 months' duration that
      evaluated the effect of drug treatment on morbidity and mortality in diabetic
      patients with hypertension. We estimated the effect of treatment with calcium
      antagonists on morbidity and mortality in comparison with placebo, conventional
      therapy, and therapy that blocks the renin-angiotensin system. RESULTS: We
      identified 14 studies that reported outcomes in diabetic hypertensive patients.
      Compared with placebo, calcium antagonists reduced cardiovascular morbidity and
      mortality. Compared with conventional therapy, calcium antagonists had similar
      effects on coronary heart disease and total mortality, but may have reduced the
      risk of stroke (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.74 to
      1.02; P = 0.08). However, they resulted in a lesser reduction of the risk of
      heart failure (OR = 1.33; 95% CI: 1.17 to 1.50). Calcium antagonists were less
      effective than blockers of the renin-angiotensin system in preventing heart
      failure (OR = 1.43; 95% CI: 1.10 to 1.84), but had similar effects on stroke,
      coronary heart disease, and total mortality. CONCLUSION: Calcium antagonists are
      safe and effective in reducing most types of cardiovascular morbidity and
      mortality in diabetic hypertensive patients, although their use is associated
      with a lesser reduction of risk of heart failure as compared with other
      treatments for hypertension.

PMID- 14706666
TI  - Fluorine 18 fluorodeoxyglucose positron emission tomography in the diagnosis and
      follow-up of three patients with vasculitis.

PMID- 14706667
TI  - Cases from the Osler Medical Service at Johns Hopkins University.

PMID- 14706669
TI  - Obesity-associated hypoventilation--a "growing" concern.

PMID- 14706670
TI  - Aortic stenosis in noncardiac surgery: underappreciated in more ways than one?

PMID- 14706671
TI  - Hypertrophic cardiomyopathy: an important global disease.

PMID- 14706672
TI  - Mucus and fatal asthma.

PMID- 14706674
TI  - Siliconoma: an unusual entity for the internist.

PMID- 14706675
TI  - Reflections on being a chair of medicine, 1993 to 2001--part 1.

PMID- 14706676
TI  - Effects of long-term high-altitude hypoxia and troponin I phosphorylation on
      cardiac myofilament calcium responses in fetal and nonpregnant sheep.
AB  - OBJECTIVE: We studied the effects of long-term high-altitude hypoxia and protein
      kinase A (PKA) phosphorylation on calcium (Ca2+) responses of skinned cardiac
      papillary muscles from fetal and adult sheep. METHODS: Fetal and nonpregnant
      adult sheep were exposed to high-altitude (3820 m), long-term (approximately 110
      days) hypoxia. Papillary muscles were isolated and mounted in well-oxygenated,
      temperature-controlled baths. After the papillary muscles were stimulated
      electrically to establish the diastolic tension that produced the maximum active
      contraction, the electrical stimulation was stopped, and the muscles were skinned
      with 1% vol/vol Triton-X-100. In protocol 1, the skinned muscles were exposed to
      activating solutions containing different calcium concentrations (pCa; from pCa
      8.0 to pCa 4.0), which were prepared by varying the Ca-EGTA/EGTA ratio, and the
      steady-state tension was measured at each pCa. In protocol 2, the skinned muscles
      were contracted with activating solution containing a pCa of 5.0. After
      equilibration, the solution in some baths was changed to activating solution at
      the same pCa of 5.0 but also containing the catalytic subunit of PKA. The other
      baths were exchanged with activating solution at a pCa of 5.0 containing no PKA.
      We then measured the degree of tension reduction caused by PKA until tension
      reached a new steady state. RESULTS: In the long-term hypoxic fetal heart, the
      maximum tension response of right, but not left, ventricular skinned papillary
      muscle to Ca2+ was significantly less than that in control muscles. In the long
      term hypoxic adult heart, the left ventricle, but not the right ventricle,
      displayed an increased maximum tension response to Ca2+ compared with control.
      Phosphorylation of troponin I (TnI) with PKA reduced active tension in both fetal
      ventricles of the long-term hypoxic group more than in hearts from control
      fetuses. In the adult, phosphorylation with PKA resulted in a larger decrease in
      tension in the left ventricle and a smaller decrease in tension in the right
      ventricle in the long-term hypoxic group, although the differences were small.
      CONCLUSION: In the long-term hypoxic fetal right ventricle, the decreased maximum
      tension response to Ca2+ is consistent with the decrease in myofibrillar
      magnesium-activated adenosine triphosphatase activity observed previously. The
      larger decrease in tension after PKA phosphorylation of TnI in the long-term
      hypoxic fetal left ventricle indicates a larger reduction in Ca2+ binding to
      troponin C.

PMID- 14706677
TI  - Creatine protects the immature brain from hypoxic-ischemic injury.
AB  - OBJECTIVE: We tested the neuroprotective effects of creatine against hypoxic
      ischemic injury in the immature brain. METHODS: Hippocampal slices were prepared
      from fetal guinea pigs at 0.9 gestation and incubated in artificial cerebrospinal
      fluid (aCSF) equilibrated with carbogen. Slices were subjected to oxygen-glucose
      deprivation (OGD) for 30 or 40 minutes. Two hours after OGD, adenosine
      triphosphate (ATP) and protein synthesis were analyzed. Creatine (3 mM) was
      applied to tissue slices of the study groups 2 hours before the insult. In a
      second set of experiments 7-day-old Wistar rats were anesthetized, and the left
      carotid artery was ligated. After 1 hour of recovery the pups were subjected to a
      hypoxic gas mixture (8% oxygen and 92% nitrogen) for 80 minutes. Seven days later
      the brains of the neonates were removed and analyzed for hypoxic-ischemic injury.
      The rat pups of the test group were treated with creatine (3 g/kg subcutaneously)
      before (-64 hours, -40 hours, and -16 hours) and after (+3 hours) the hypoxic
      ischemic insult, with zero time corresponding to the start of hypoxia, whereas
      the animals of the control group received the solvent. RESULTS: Creatine
      significantly improved the recovery of protein synthesis 2 hours after OGD in
      hippocampal slices but had no effect on ATP levels. Whereas seven animals of the
      control group developed severe cystic cerebral infarction, only mild to moderate
      damage was observed in the rat pups of the study group. In contrast to creatine
      treated pups, the volume of the ipsilateral hemisphere was considerably smaller
      than that of the contralateral one in control animals (104 +/- 22 versus 138 +/-
      14 mL, P<.001). Except at the frontal level (A 6.0 mm), neuronal cell injury was
      significantly lower in the cortex of the animals that had received creatine. This
      was also true for the evaluated subfields in the hippocampus. CONCLUSION: We
      conclude that creatine protects the immature brain from hypoxic-ischemic injury.

PMID- 14706678
TI  - Endothelin and the regulation of uterine and placental perfusion in hypoxia
      induced fetal growth restriction.
AB  - OBJECTIVE: Normal placental function is dependent on maintenance of
      uteroplacental perfusion. Endothelin, a potent vasoconstrictor, is produced in
      and is active in the uteroplacental vasculature. The purpose of this study was to
      determine the role of endothelin in the regulation of uteroplacental perfusion
      under normal conditions, and in hypoxia-induced fetal growth restriction.
      METHODS: Timed-pregnant Sprague-Dawley rats, outfitted with arterial catheters,
      were maintained in either a normoxic or a normobaric hypoxic (12% oxygen)
      atmosphere from day 18 to 21 of gestation. During this time, the endothelin
      receptor A antagonist, A-127722, or its vehicle was administered. Regional blood
      flow was determined on gestational day 21 using 57Co-labeled microspheres. Data
      were analyzed by analysis of variance with statistical significance accepted at
      P<.05. RESULTS: Both placental and uterine placental bed perfusion were
      significantly decreased by hypoxia and returned to normal values with the
      endothelin antagonist (P<.01 and P<.05, respectively). Fetal weights were
      significantly lower in the hypoxic group (P<.001) and restored to control levels
      by the antagonist. CONCLUSION: In the rat, endothelin contributes little to the
      regulation of uteroplacental perfusion under normal conditions. Hypoxia results
      in a decrease in perfusion of the uteroplacental bed and of the placenta, and
      perfusion in both of these beds is normalized by endothelin A receptor
      antagonism. We conclude that endothelin plays a primary role in the
      pathophysiology of hypoxia-induced fetal growth restriction by reducing
      uteroplacental perfusion.

PMID- 14706679
TI  - Effects of dexamethasone and sulfasalazine on prostaglandin E2 output by human
      placental cells in vitro.
AB  - OBJECTIVE: Prostaglandins (PG) are key mediators of the labor process. We
      investigated effects of dexamethasone on PGE2 output in term human placental
      cells in the presence of indomethacin, an inhibitor of PGH synthase enzymes PGHS1
      and PGHS2 activity; meloxicam, a relatively specific inhibitor of PGHS2; and
      sulfasalazine, an inhibitor of 15-OH PG dehydrogenase (PGDH), a PG-metabolizing
      enzyme. METHODS: Cells were treated for 24 hours with indomethacin (1 microM),
      meloxicam (1 microM), sulfasalazine (1 microM), or combinations of these three
      compounds in the presence or absence of glucocorticoids. RESULTS: Meloxicam alone
      had no effect on basal output of PGE2. Dexamethasone produced a significant,
      almost doubling of PGE2 output, but this was not altered further by meloxicam.
      Sulfasalazine alone doubled the output of PGE2, and this increased further in the
      presence of dexamethasone. That increase was reduced by addition of meloxicam.
      Indomethacin significantly reduced stimulation of PGE2 output measured after
      dexamethasone treatment. In addition, indomethacin significantly attenuated the
      stimulation of PGE2 output seen with the addition of sulfasalazine or the further
      increase seen with sulfasalazine plus dexamethasone. CONCLUSION: Basal PGE2
      output by placental cells likely depends on the activity of PGHS1, not PGHS2. The
      effects of sulfasalazine suggest the importance of endogenous PGDH in regulating
      PGE2 output, and interactions with sulfasalazine, dexamethasone, and meloxicam
      suggest that glucocorticoid-stimulated output of PGE2 by placental cells may be
      attributable to both up-regulation of PGHS and down-regulation of PGDH.

PMID- 14706680
TI  - Developmental aspects of ovine adrenal adrenocorticotropic hormone receptor
      expression.
AB  - OBJECTIVE: Maturation of adrenocortical function is important because a prepartum
      increase in fetal plasma glucocorticoids is required for survival after birth.
      Adrenal maturation may include alterations in the regulation of
      adrenocorticotropic hormone (ACTH) receptor expression. Therefore, we quantitated
      ACTH receptor expression in the ovine adrenal cortex during development and after
      manipulations to better understand the regulation of the adrenal receptor in
      vivo. METHODS: For the ontogeny study, adrenals were obtained from fetuses at
      different stages of development, and the cortical tissue was stored at -80C until
      total RNA was extracted. The ACTH binding studies were done on adrenal membranes
      obtained from fetuses at two different ages using I125 (Phe-2, Nle-4) ACTH as the
      ligand. Plasma ACTH was measured by two-site immunoradiometric assay, and
      cortisol was measured by radioimmunoassay. ACTH receptor mRNA was quantitated by
      ribonuclease protection assay. The data were analyzed by analyses of variance.
      RESULTS: ACTH receptor mRNA level progressively increased in fetal life; relative
      changes in receptor mRNA and binding were similar (3.0-fold and 2.4-fold,
      respectively). Physiologic increases in fetal plasma cortisol decreased adrenal
      ACTH receptor mRNA concentration, and there was a strong (r2=0.76, P<.002) linear
      relationship between fetal plasma ACTH concentration and receptor mRNA levels.
      Receptor mRNA stability increased in development, and message half-life was
      greater in adulthood than in fetal life. CONCLUSION: The data suggest that
      developmental increases in receptor expression are part of the maturation process
      in the fetal adrenal and that plasma ACTH concentration plays a major role in
      regulating ACTH receptor mRNA levels in vivo.

PMID- 14706681
TI  - Influence of maternal diabetes on placental fibroblast growth factor-2
      expression, proliferation, and apoptosis.
AB  - OBJECTIVE: Type I diabetes mellitus during pregnancy is associated with
      dysregulation of the oxygen and glucose metabolic pathways, both of which affect
      placental villous growth and function. Alteration of placental development in
      women with diabetes may contribute to the increased risk of preeclampsia,
      macrosomia, or fetal growth restriction. METHODS: To evaluate placental growth in
      the setting of maternal diabetes, immunohistochemical techniques were used to
      examine fibroblast growth factor-2 (FGF-2) expression, cell proliferation (Ki67),
      and apoptosis (Apo-Tag) in placentas from diabetic and nondiabetic patients.
      RESULTS: Immunostaining for FGF-2 in placentas from diabetic women demonstrated
      an increase in intensity within the villous stroma and syncytiotrophoblast
      (P<.05). Associated with these changes in FGF-2 expression, placentas from
      diabetic women showed no change in villous mitotic activity but did show
      decreased stromal compartment apoptosis. When expressed as a ratio of Ki67
      positive:Apo-Tag-positive nuclei as an index of relative cell turnover, the
      stromal compartment showed a significant trend towards decreased nuclei turnover
      (P<.05), suggesting relative tissue growth in diabetic patients. CONCLUSION:
      Increased FGF-2 expression and decreased stromal cell compartment turnover in the
      diabetic placenta might be a compensatory mechanism in response to the altered
      physiologic milieu of maternal diabetes on placental function.

PMID- 14706682
TI  - Genetic polymorphisms associated with thrombophilia and vascular disease in women
      with unexplained late intrauterine fetal death: a multicenter study.
AB  - OBJECTIVE: We determined whether gene polymorphisms associated with thrombophilia
      and vascular disease as etiologic factors were involved in the pathogenesis of
      pregnancy-associated complications. METHODS: We conducted a multicenter case
      control study in which we studied 94 women with late unexplained intrauterine
      fetal death (IUFD) and 94 healthy women with at least one uncomplicated full-term
      pregnancy and no history of IUFD. We obtained blood samples from all subjects and
      analyzed their DNA for 12 common polymorphisms of thrombophilic and vascular
      genes (factor V Leiden, factor V H1299R, prothrombin G20210A, factor XIII V34L,
      MTHFR C677T, MTHFR A1298C, beta-fibrinogen-455 G to A, PAI-1 4G/5G, GPIIIa L33P,
      HFE C282Y, apolipoprotein B R3500Q, and apolipoprotein E2/E3/E4). RESULTS: We
      found no significant association between any of the polymorphisms investigated
      and IUFD. Subgroup analyses involving various combinations of polymorphisms and
      in which gestational age and fetal weight were corrected for also showed no
      significant results. CONCLUSIONS: Our data represent the largest study to date
      with respect to thrombophilic and vascular gene polymorphisms in IUFD. In
      accordance with others, we challenge the importance of thrombophilic and vascular
      gene polymorphisms in the pathogenesis of this condition.

PMID- 14706683
TI  - Renal handling of homocysteine during normal pregnancy and preeclampsia.
AB  - OBJECTIVE: Maternal plasma homocysteine decreases in normal pregnancy and is
      significantly increased in preeclampsia. The goal of this study was to
      investigate the role of the maternal kidney in the changes of plasma homocysteine
      during normal pregnancy and preeclampsia. METHODS: Plasma and 24-hour urine
      samples were collected in the same women before, during (first, second, and third
      trimesters), and after normal pregnancy; and in a separate cross-sectional study
      of normal pregnant, preeclamptic and nonpregnant women and homocysteine
      concentrations were measured. RESULTS: Longitudinally, maternal plasma
      homocysteine decreased significantly by the first trimester compared with
      prepregnancy and postpartum levels (5.6 +/- 1.8 versus 6.8 +/- 0.5 and 7.4 +/-
      0.4 microM, respectively, P<.05 by analysis of variance) and paralleled a
      significant increase in the renal clearance of homocysteine (2.9 +/- 0.4 versus
      1.8 +/- 0.2 and 1.6 +/- 0.2 L/24 hours, respectively, P<.001). In addition,
      plasma homocysteine was significantly elevated in preeclampsia compared with
      normal pregnancy (4.4 +/- 0.6 versus 3.2 +/- 0.2 microM, P<.04); however, renal
      clearance was not different (1.2 +/- 0.1 versus 1.0 +/- 0.1 L/24 hours, P=.55).
      CONCLUSION: Increases in renal clearance contribute to the decrease in plasma
      homocysteine during normal pregnancy. However, changes in renal handling do not
      appear to contribute to the increase in plasma homocysteine in preeclampsia.

PMID- 14706684
TI  - Gene expression patterns that characterize advanced stage serous ovarian cancers.
AB  - OBJECTIVE: To identify gene expression patterns that characterize advanced stage
      serous ovarian cancers by using microarray expression analysis. METHODS: Using
      genome-wide expression analysis, we compared a series of 31 advanced stage (III
      or IV) serous ovarian cancers from patients who survived either less than 2 years
      or more than 7 years with three normal ovarian epithelial samples. Array findings
      were validated by analysis of expression of the insulin-like growth factor
      binding protein 2 (IGFBP2) and tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) genes using quantitative real-time polymerase chain reaction (QRT
      PCR). RESULTS: Hierarchical clustering identified patterns of gene expression
      that distinguished cancer from normal ovarian epithelium. We also identified gene
      expression patterns that distinguish cancers on the basis of patient survival.
      These genes include many that are associated with immune function. Expression of
      IGFBP2 and TRAIL genes measured by array and QRT-PCR analysis demonstrated
      correlation coefficients of 0.63 and 0.78, respectively. CONCLUSION: Global
      expression analysis can identify expression patterns and individual genes that
      contribute to ovarian cancer development and outcome. Many of the genes that
      determine ovarian cancer survival are associated with the immune response,
      suggesting that immune function influences ovarian cancer virulence. With the
      generation of newer arrays with more transcripts, larger studies are possible to
      fully characterize genetic signatures that predict survival that may ultimately
      be used to guide therapeutic decision-making.

PMID- 14706685
TI  - Emergence of neural net function during brain development.

PMID- 14706686
TI  - Cadherins as regulators for the emergence of neural nets from embryonic
      divisions.
AB  - Cadherins are a large family of cell adhesion molecules that are expressed in a
      spatially restricted fashion during vertebrate CNS development. Each cadherin
      shows a characteristic expression pattern that differs from that of other
      cadherins. Early in development, the cadherin expression domains relate to the
      neuromeric organization of the vertebrate CNS. Later, as functional structures
      (brain nuclei, cortical regions, fiber tracts and synapses) emerge, the
      expression patterns of each cadherin become restricted to subsets of these
      structures that form parts of specific neural nets. Cadherins thus represent a
      system of potentially adhesive cues that play a role in the emergence of neural
      nets from embryonic CNS divisions. We review descriptive and experimental
      evidence for such a role of cadherins in CNS development. It is argued that
      descriptive studies (i.e., the mapping of gene expression) and functional studies
      (i.e., experimental manipulation of gene expression) are equally important for
      generating specific and firm ideas on the function of genes in brain development.

PMID- 14706687
TI  - The development of vestibulo-ocular circuitry in the chicken embryo.
AB  - This article reviews studies of the organization and development of the vestibulo
      ocular reflex arc in the chicken embryo. It summarizes some of the principal
      features that characterize the development of this circuit, including the gradual
      clustering of motoneurons in the oculomotor nucleus into functionally
      identifiable motoneuron pools, the patterning of vestibular projection neurons
      into coherent clusters with specific axonal trajectories and terminations onto
      the oculomotor motoneuron pools, the reverse order of synapse formation during
      development (motoneuron to muscle, then vestibular projection neuron to
      motoneuron), and the selectivity of initial synaptic termination at both the
      ultimate and penultimate relays within the reflex arc. Reference to studies in
      other vertebrate species is made to provide a comparative context, and potential
      mechanisms are discussed that may contribute to the underlying synaptic
      specificity in this circuit.

PMID- 14706688
TI  - Developmental patterns and plasticities: the hippocampal model.
AB  - Because developmental activity-dependent synaptic plasticity has been
      hypothesized to participate in network refinement, leading to the precise mapping
      of synaptic contacts constituting a functional brain, it is important to
      investigate the spatio-temporal structure of immature network activities. This
      article is briefly reviewing 15 years of studies on the immature rat hippocampus
      which, together with recent results obtained from awake rat pups, represent an
      important step toward the understanding of spontaneous patterns of activity and
      their potential implication in network maturation. Due to synergistic excitatory
      actions of GABA and glutamate receptor mediated signals during early postnatal
      life, spontaneous patterns of hippocampal activity that have been characterized
      both in vitro and in vivo are likely to provide hebbian modulation of developing
      glutamatergic and GABAergic synapses. Together with studies on trophic actions of
      these transmitters, study of the immature hippocampal network patterns and
      plasticities allows for multiple technical and conceptual approaches and
      represents an interesting experimental model for development studies.

PMID- 14706689
TI  - Nitric oxide and its influence on oscillations of collicular responses in
      developing rats.
AB  - We investigated the influence of modulating NO synthesis on oscillatory
      components of ON and OFF evoked field potentials in developing rat superior
      colliculus. Nitric oxide (NO) is involved in neuronal transmission by adjusting
      neurotransmitter release in adults and in stabilizing synaptic connections in
      developing brains. NO synthesis was decreased by inhibiting nitric oxide synthase
      (NOS) with an acute microinjection of N-nitro-L-arginine methyl ester (L-NAME);
      whereas NO synthesis was augmented by an acute microinjection of L-arginine (L
      ARG). The study is focused on rhythmic activity by analyzing fast Fourier
      transform (FFT). Collicular responses were recorded in anesthetized rats, at post
      natal days (PND) 13-19 and adults. This time window was chosen because it is
      centered on eye opening. NO down- and upregulation resulted in a dual effect
      depending on age and response-type. NO synthesis inhibition decreased the
      magnitude of oscillations in ON responses in the youngest animals (PND13-PND14),
      whereas oscillations of frequencies higher than 20 Hz in OFF responses were
      increased in all age groups of developing rats. In adults NO downregulation
      increased oscillations in ON responses and decreased oscillations in OFF
      responses. L-arginine application produced effects opposite to those seen with L
      NAME. Our data together with results reported in the literature suggest that the
      temporal patterns of the evoked activity are NO-dependent. This sculpting action
      of the evoked firing may play a role in the synchronization of action potentials
      in afferent axons which in turn contributes to synaptic stabilization.

PMID- 14706690
TI  - Expression of K(Ca) channels in identified populations of developing vertebrate
      neurons: role of neurotrophic factors and activity.
AB  - Changes in the intrinsic spike discharge properties in one neuronal population
      can alter the functions and even the formation of an entire neuronal network.
      Therefore it is important to understand the factors that regulate acquisition of
      a mature electrophysiological phenotype. Here we focus on large-conductance K(Ca)
      channels, which shape the pattern of repetitive discharge and which are therefore
      likely to play a role in the refinement of neural networks during development. In
      the parasympathetic ciliary ganglion of chick, the developmental expression of
      K(Ca) channels coincides with stages at which ciliary cells form synapses with
      target tissues. Moreover, K(Ca) expression requires formation of synapses with
      target tissues, and with afferent preganglionic inputs. The trophic effect of
      targets is mediated by TGFbeta1, whereas the effect of the preganglionic input is
      mediated by an isoform of beta-neuregulin-1. These trophic factors act
      synergistically, and this appears to be a normal feature of their actions in
      vivo. The acute effects of TGFbeta1 entail translocation of preexisting K(Ca)
      channels from intracellular stores to the plasma membrane. This requires
      activation of the signaling enzymes Ras, Erk MAP kinase and PI3 kinase. TGFbeta1
      also causes a more sustained increase in K(Ca) channels (i.e. for up to 2 weeks)
      that requires synthesis of new channel proteins. Inductive regulation of K(Ca)
      expression is also observed in CNS cells that form more complex networks. In
      lumbar motoneurons, the largest changes in K(Ca) expression coincide with the
      elimination of synapses with hindlimb targets. Interactions with target tissues
      play a key role in regulation of motoneuron K(Ca) expression, and this trophic
      effect of target muscle is mediated by GDNF or a closely related factor. In
      addition, K(Ca) expression in motoneurons is dependent on ongoing electrical
      activity both in vivo and in vitro. This provides an additional mechanism for use
      dependent refinement of neural networks during embryonic development.

PMID- 14706691
TI  - Maturation of rhythmic neural network: role of central modulatory inputs.
AB  - Modulatory systems are well known for their roles in tuning the cellular and
      synaptic properties in the adult neuronal networks, and play a major role in the
      control of the flexibility of functional outputs. However far less is known
      concerning their role in the maturation of neural networks during the
      development. In this review, using the stomatogastric nervous system of lobster,
      we will show that the neuromodulatory system exerts a powerful influence on
      developing neural networks. In the adult the number of both motor target neurons
      and their modulatory neurons is restricted to tens of identifiable cells. They
      are therefore well characterized in terms of cellular, synaptic and morphological
      properties. In the embryo, these target cells and their neuromodulatory
      population are already present from mid-embryonic life. However, the motor output
      generated by the system is quite different: while in the embryo all the target
      neurons are organized into a single network generating unique motor pattern, in
      the adult this population splits into two distinct networks generating separate
      patterns. This ontogenetic partitioning does not rely on progressive acquisition
      of adult properties but rather on a switch between two possible network
      operations. Indeed, adult networks are present early in the embryonic life but
      their expression is repressed by central modulatory neurons. Moreover, embryonic
      networks can be revealed in the adult system again by altering modulatory
      influences. Therefore, independently of the developmental age, two potential
      network phenotypes co-exist within the same neuronal architecture: when one is
      expressed, the other one is hidden and vice versa. These transitions do not
      necessarily need dramatic changes such as growth/retraction of processes,
      acquisition of new intra-membrane proteins etc. but rather, as shown by modelling
      studies, it may simply rely on a subtle tuning of pre-existing intercellular
      electrical coupling. This in turn suggests that progressive ontogenetic
      alteration may not take place at the level of the target network but rather at
      the level of modulatory input neurons.

PMID- 14706692
TI  - A molluscan model system in the search for the engram.
AB  - A 3-neuron central pattern generator, whose sufficiency and necessity has been
      directly demonstrated, mediates aerial respiratory behaviour in the pond snail,
      Lymnaea stagnalis. This behaviour can be operantly conditioned, and this
      associative learning is consolidated into long-lasting memory. Depending on the
      operant conditioning training procedure used the learning can be consolidated
      into intermediate term (ITM) or long-term memory (LTM). ITM persists for only 2-3
      h, whilst LTM persists for days to weeks. LTM is dependent on both altered gene
      activity and new protein synthesis while ITM is only dependent on new protein
      synthesis. We have now directly established that one of the 3-CPG neurons, RPeD1,
      is a site of LTM formation and storage. We did this by ablating the soma of RPeD1
      and leaving behind a functional primary neurite capable of mediating the
      necessary synaptic interactions to drive aerial respiratory behaviour by the 3
      neuron CPG. However, following soma ablation the neuronal circuit is only capable
      of mediating learning and ITM. LTM can no longer be demonstrated. However, if
      RPeD1's soma is ablated after LTM consolidation memory is still present. Thus the
      soma is not needed for the retention of LTM. Using a similar strategy it may be
      possible to block forgetting.

PMID- 14706693
TI  - Steps during the development of the zebrafish locomotor network.
AB  - This review summarizes recent data from our lab concerning the development of
      motor activities in the developing zebrafish. The zebrafish is a leading model
      for studies of vertebrate development because one can obtain a large number of
      transparent, externally and rapidly developing embryos with motor behaviors that
      are easy to assess (e.g. for mutagenic screens). The emergence of embryonic
      motility was studied behaviorally and at the cellular level. The embryonic
      behaviors appear sequentially and include an early, transient period of
      spontaneous, alternating tail coilings, followed by responses to touch, and
      swimming. Patch clamp recording in vivo revealed that an electrically coupled
      network of a subset of spinal neurons generates spontaneous tail coiling, whereas
      a chemical (glutamatergic and glycinergic) synaptic drive underlies touch
      responses and swimming and requires input from the hindbrain. Swimming becomes
      sustained in larvae once serotonergic neuromodulatory effects are integrated. We
      end with a brief overview of the genetic tools available for the study of the
      molecular determinants implicated in locomotor network development in the
      zebrafish. Combining genetic, behavioral and cellular experimental approaches
      will advance our understanding of the general principles of locomotor network
      assembly and function.

PMID- 14706695
TI  - Nestin expression in pancreatic exocrine cell lineages.
AB  - Expression of nestin has been suggested to be a characteristic of pancreatic
      islet stem cells. To determine whether nestin is indeed expressed in such
      putative cells during embryonic development, or in the adult pancreas after
      injury, we performed a cell lineage analysis using two independent lines of
      transgenic mice encoding Cre recombinase under the control of rat nestin cis
      regulatory sequences, each crossed with loxP-bearing R26R mice. F1 animals
      produced the reporter molecule beta-galactosidase only upon Cre-mediated
      recombination, thus solely in cells using (or having used) the transgenic nestin
      promoter. In early pancreatic primordia, beta-galactosidase was observed in
      mesenchymal and epithelial cells. At later developmental stages or in adults,
      vast clusters of acinar cells and few ductal cells were labeled, in addition to
      fibroblasts and vascular cells, but no endocrine cells were tagged by beta
      galactosidase. This correlated with the transient expression, observed with an
      anti-nestin antibody, of endogenous nestin in about 5% of epithelial cells during
      development (whether in cord-forming arrangements or in nascent acini), and in
      vascular and mesenchymal structures. After partial pancreatectomy, there was a
      transient increase of the number of anti-nestin-labeled endothelial cells, but
      again, no endocrine cells bore beta-galactosidase. Together, these findings show
      that nestin is expressed in the pancreatic exocrine cell lineage, and suggest
      that consistent nestin expression is not a major feature of islet endocrine
      progenitor cells.

PMID- 14706696
TI  - Origin of exocrine pancreatic cells from nestin-positive precursors in developing
      mouse pancreas.
AB  - During pancreatic development, endocrine and exocrine cell types arise from
      common precursors in foregut endoderm. However, little information is available
      regarding regulation of pancreatic epithelial differentiation in specific
      precursor populations. We show that undifferentiated epithelial precursors in
      E10.5 mouse pancreas express nestin, an intermediate filament also expressed in
      neural stem cells. Within developing pancreatic epithelium, nestin is co
      expressed with pdx1 and p48, but not ngn3. Epithelial nestin expression is
      extinguished upon differentiation of endocrine and exocrine cell types, and no
      nestin-positive epithelial cells are observed by E15.5. In E10.5 dorsal bud
      explants, activation of EGF signaling results in maintenance of undifferentiated
      nestin-positive precursors at the expense of differentiated acinar cells,
      suggesting a precursor/progeny relationship between these cell types. This
      relationship was confirmed by rigorous lineage tracing studies using nestin
      regulatory elements to drive Cre-mediated labeling of nestin-positive precursor
      cells and their progeny. These experiments demonstrate that a nestin
      promoter/enhancer element containing the second intron of the mouse nestin locus
      is active in undifferentiated E10.5 pancreatic epithelial cells, and that these
      nestin-positive precursors contribute to the generation of differentiated acinar
      cells. As in neural tissue, nestin-positive cells act as epithelial progenitors
      during pancreatic development, and may be regulated by EGF receptor activity.

PMID- 14706697
TI  - Ce-Y14 and MAG-1, components of the exon-exon junction complex, are required for
      embryogenesis and germline sexual switching in Caenorhabditis elegans.
AB  - Y14 is a component of the splicing-dependent exon-exon junction complex (EJC) and
      is involved in the mRNA quality control system called nonsense-mediated mRNA
      decay. It has recently been shown that together with another EJC component, Mago,
      the Drosophila homologue DmY14/Tsunagi is required for proper localization of
      oskar mRNA during oogenesis, a process critical for posterior formation in
      Drosophila development. Here we show that the nematode Caenorhabditis elegans Ce
      Y14 and MAG-1 (Mago homologue) are required for late embryogenesis and proper
      germline sexual differentiation. Like in other organisms, Ce-Y14 preferentially
      binds to spliced mRNA and specifically interacts with MAG-1. Consistent with the
      evolutionarily conserved interaction between Y14 and Mago homologues, suppression
      of Ce-Y14 by RNAi resulted in the same phenotypes as those caused by RNAi of mag
      1 lethality during late embryogenesis and masculinization of the adult
      hermaphrodite germline. Our results demonstrate that the evolutionarily conserved
      interaction between two EJC components, Ce-Y14 and MAG-1, has critical
      developmental roles in C. elegans.

PMID- 14706698
TI  - The grainy head transcription factor is essential for the function of the
      frizzled pathway in the Drosophila wing.
AB  - The Drosophila wing is covered by an array of distally pointing hairs. This
      tissue planar polarity is regulated by the frizzled pathway. We have found that
      the function of the grainy head transcription factor is essential for the
      function of the frizzled pathway. grainy head mutant cells fail to localize
      planar polarity proteins at either the proximal or distal sides of wing cells and
      produce multiple hairs of abnormal polarity. Levels of the Starry night protein
      are strongly reduced in grainy head mutants in both larval wing discs and pupal
      wings, which is sufficient to account for much of the polarity phenotype. In
      addition, we found that grh has frizzled pathway independent functions during the
      development of the adult cuticle.

PMID- 14706699
TI  - The MADS-box transcription factor SrfA is required for actin cytoskeleton
      organization and spore coat stability during Dictyostelium sporulation.
AB  - The MADS-box transcription factor SrfA is involved in spore differentiation in
      Dictyostelium [Development 125 (1998) 3801]. Mutant spores show an altered
      morphology and loss of viability. A detailed structural analysis of mutant spores
      has been performed to gain insight into the specific aspects of spore
      differentiation in which SrfA is involved. Two main structural defects have been
      observed. One is the formation of high order actin structures, the so-called
      actin rods. SrfA mutant spores showed the initial stages of rod formation but no
      mature rods were found in older spores either in the nucleus or the cytoplasm.
      Moreover, phosphorylation of actin, that is believed to stabilize the actin rods,
      is strongly reduced in the mutant. The other defect observed was the formation of
      the spore coat. Young srfA- spores show basically normal trilaminar coat
      structures suggesting that release of prespore vesicles and basic assembly of the
      coat takes place in the absence of SrfA. However, the outer layer gets wavier as
      the spore ages and suffers a progressive degradation suggesting a late defect in
      the stability of the spore coat. Taken together, these results suggest that SrfA
      is involved in late events of spore maturation necessary for spore stability.

PMID- 14706700
TI  - Cortactin modulates cell migration and ring canal morphogenesis during Drosophila
      oogenesis.
AB  - Cortactin is a Src substrate that interacts with F-actin and can stimulate actin
      polymerization by direct interaction with the Arp2/3 complex. We have isolated
      complete loss-of-function mutants of the single Drosophila cortactin gene.
      Mutants are viable and fertile, showing that cortactin is not an essential gene.
      However, cortactin mutants show distinct defects during oogenesis. During
      oogenesis, Cortactin protein is enriched at the F-actin rich ring canals in the
      germ line, and in migrating border cells. In cortactin mutants, the ring canals
      are smaller than normal. A similar phenotype has been observed in Src64 mutants
      and in mutants for genes encoding Arp2/3 complex components, supporting that
      these protein products act together to control specific processes in vivo.
      Cortactin mutants also show impaired border cell migration. This invasive cell
      migration is guided by Drosophila EGFR and PDGF/VEGF receptor (PVR). We find that
      accumulation of Cortactin protein is positively regulated by PVR. Also,
      overexpression of Cortactin can by itself induce F-actin accumulation and ectopic
      filopodia formation in epithelial cells. We present evidence that Cortactin is
      one of the factors acting downstream of PVR and Src to stimulate F-actin
      accumulation. Cortactin is a minor contributor in this regulation, consistent
      with the cortactin gene not being essential for development.

PMID- 14706701
TI  - Programmed cell death and context dependent activation of the EGF pathway
      regulate gliogenesis in the Drosophila olfactory system.
AB  - In the Drosophila antenna, sensory lineages selected by the basic helix-loop
      helix transcription factor Atonal are gliogenic while those specified by the
      related protein Amos are not. What are the mechanisms that cause the two lineages
      to act differentially? We found that ectopic expression of the Baculovirus
      inhibitor of apoptosis protein (p35) rescues glial cells from the Amos-derived
      lineages, suggesting that precursors are removed by programmed cell death. In the
      wildtype, glial precursors express the extracellular-signal regulated kinase
      transiently, and antagonism of Epidermal Growth Factor (EGF) pathway signaling
      compromises their development. We suggest that all sensory lineages on the
      antenna are competent to produce glia but only those specified by Atonal respond
      to EGF signaling and survive. These results underscore the importance of
      developmental context of cell lineages in their responses to non-autonomous
      signaling in the choice between survival and death.

PMID- 14706702
TI  - Zebrafish maternal-effect mutations causing cytokinesis defect without affecting
      mitosis or equatorial vasa deposition.
AB  - Maternal-effect genes play essential roles in early embryogenesis particularly
      before activation of the zygotic genes. A genetic screen for mutations affecting
      such maternal-effect genes was carried out employing an F3 screen strategy,
      identifying six recessive mutations out of 60 mutagenized genomes. Three of the
      mutations (acytokinesis mutations: ackkt5, ackkt62 and ackkt119) caused absence
      of cell cleavage in the embryos derived from homozygous females regardless of the
      paternal genotype, without affecting nuclear divisions. These embryos are
      defective in generating contractile rings, ackkt62 mutation abolishing reactions
      to organize cortical F-actin, while other mutations causing abortive contractile
      ring-like structures at ectopic sites. Defect of contractile ring formation in
      the affected embryos leads to the absence of microtubule arrays at the
      prospective cleavage plane. Thus, these mutations reveal the sequence of events
      associated with cytokinesis, in particular, the cortical actin dynamics. It is
      remarkable that in all acytokinetic embryos, daughter nuclei after mitosis are
      arranged in spatially normal positions, and maternal vasa mRNAs accumulate in the
      prospective planes of the first and second cell cleavages in the total absence of
      cytokinesis. This indicates that the basic cell architectures of early embryos
      are largely established by the autonomous activities of the mitotic apparatus,
      without much dependence on the cell cleavage machinery.

PMID- 14706703
TI  - Biogenesis and function of mouse mammary epithelium depends on the presence of
      functional alpha-catenin.
AB  - Alpha-catenin is a structural molecule and essential to the function of
      epithelial adherens junctions. Its role in the morphogenesis of mammary
      epithelium was explored using experimental mouse genetics. Since loss of alpha
      catenin in mice leads to embryonic lethality, the alpha-catenin gene was flanked
      by loxP sites and inactivated in mammary epithelium using the WAP-Cre and MMTV
      Cre transgenes. Loss of alpha-catenin arrested alveolar epithelial expansion.
      These cells lacked proper polarity and markers of functional differentiation,
      which resulted in impaired milk protein gene expression. Without alpha-catenin,
      increased epithelial cell death was observed at parturition and the tissue
      resembled an involuted gland that is normally observed after weaning. Lastly, no
      tumors were detected in mammary tissue lacking alpha-catenin.

PMID- 14706704
TI  - Conserved and clustered RNA recognition sequences are a critical feature of
      signals directing RNA localization in Xenopus oocytes.
AB  - Although it is widely regarded that the targeting of RNA molecules to subcellular
      destinations depends upon the recognition of cis-elements found within their 3'
      untranslated regions (UTR), relatively little is known about the specific
      features of these cis-sequences that underlie their function. Interaction between
      specific repeated motifs within the 3' UTR and RNA-binding proteins has been
      proposed as a critical step in the localization of Vg1 RNA to the vegetal pole of
      Xenopus oocytes. To understand the relative contributions of repeated
      localization element (LE) sequences, we used comparative functional analysis of
      Vg1 LEs from two frog species, Xenopus laevis and Xenopus borealis. We show that
      clusters of repeated VM1 and E2 motifs are required for efficient localization.
      However, groups of either site alone are not sufficient for localization. In
      addition, we present evidence that the X. borealis Vg1 LE is recognized by the
      same set of RNA-binding proteins as the X. laevis Vg1 LE and is capable of
      productive interactions with the X. laevis transport machinery as it is
      sufficient to direct vegetal localization in X. laevis oocytes. These results
      suggest that clustered sets of cis-acting sites within the LE direct vegetal
      transport through specific interactions with the localization machinery.

PMID- 14706709
TI  - MRCI: a flexible real-time dynamic clamp system for electrophysiology
      experiments.
AB  - We present a real-time simulation system that enables modeled dynamical systems
      to interact with physical experimental systems, and is specifically aimed towards
      execution of the dynamic clamp protocol. Model reference current injection (MRCI)
      operates under Real-Time Linux (RT-Linux or RTL) and provides a simple equation
      oriented language for describing dynamical system models. Features include
      scripting of commands to implement repeatable protocols, the ability to output
      pre-computed waveforms through any variable or parameter of the model, the means
      to conduct time measurements and assess the computational performance of the real
      time system, and an installation program that installs the software and
      accompanying device drivers with minimal input from the user. Tested models
      operate as fast as 30 kHz, with actual maximum rates dependent on model
      complexity. We present sample models that exhibit the main features of the
      modeling language. Experiments demonstrate the abilities of the system by
      creating a hybrid network of real and simulated neurons, and playing a pre
      defined synaptic waveform into a synaptic conductance variable. We conclude by
      introducing a waveform reconstruction technique that is useful for establishing
      the presence of significant experimental error in implementations of the dynamic
      clamp protocol.

PMID- 14706710
TI  - A dual RF resonator system for high-field functional magnetic resonance imaging
      of small animals.
AB  - A new apparatus has been developed that integrates an animal restrainer
      arrangement for small animals with an actively tunable/detunable dual radio
      frequency (RF) coil system for in vivo anatomical and functional magnetic
      resonance imaging of small animals at 4.7 T. The radio-frequency coil features an
      eight-element microstrip line configuration that, in conjunction with a segmented
      outer copper shield, forms a transversal electromagnetic (TEM) resonator
      structure. Matching and active tuning/detuning is achieved through fixed/variable
      capacitors and a PIN diode for each resonator element. These components along
      with radio-frequency chokes (RFCs) and blocking capacitors are placed on two
      printed circuit boards (PCBs) whose copper coated ground planes form the front
      and back of the volume coil and are therefore an integral part of the resonator
      structure. The magnetic resonance signal response is received with a dome-shaped
      single-loop surface coil that can be height-adjustable with respect to the
      animal's head. The conscious animal is immobilized through a mechanical
      arrangement that consists of a Plexiglas body tube and a head restrainer. This
      restrainer has a cylindrical holder with a mouthpiece and position screws to
      receive and restrain the head of the animal. The apparatus is intended to perform
      anatomical and functional magnetic resonance imaging in conscious animals such as
      mice, rats, hamsters, and marmosets. Cranial images acquired from fully conscious
      rats in a 4.7 T Bruker 40 cm bore animal scanner underscore the feasibility of
      this approach and bode well to extend this system to the imaging of other
      animals.

PMID- 14706711
TI  - Design and application of a novel brain slice system that permits independent
      electrophysiological recordings from multiple slices.
AB  - We describe a novel brain slice system 'SliceMaster' that allows
      electrophysiological recordings from eight brain slices independently. The system
      consists of two autonomous units each supporting four modular brain slice
      chambers enabling high signal-to-noise ratio recordings, each chamber has one
      stimulation electrode, one recording electrode, a twin camera system and a
      solution application system. The positioning of both electrodes and cameras are
      controlled from a remote user console. The software both acquires and performs on
      line analysis of the data. We have demonstrated utility of this system in
      obtaining recordings of spontaneous firing activity and evoked synaptic activity
      from mouse hippocampal slices, with reduced variability within and between
      experiments. Furthermore, we show recordings of population spikes from the
      perirhinal cortex, indicating applicability of this system for further brain
      regions. In addition, stable recordings could be maintained until recording was
      terminated after 3 h, permitting investigation of the induction and maintenance
      of synaptic plasticity. Recordings of spontaneous and synaptic activity, and
      effects of pharmacological and electrophysiological manipulation, were consistent
      with reports using conventional methods. However, the described system permits
      concurrent and independent recordings from eight brain slices, thus improving
      throughput, statistical design, and reducing animal use.

PMID- 14706712
TI  - Novel strategy to study gene expression and function in developing cerebellar
      granule cells.
AB  - The advent of techniques for global analyses of cell biology, such as genomics
      and proteomics, opens the way to rapid progress in understanding the molecular
      control of developing tissues. However, such studies in the CNS are hindered by
      the complexity of this tissue. In particular, few approaches allow cells to be
      isolated that are enriched for specific stages of their maturation. We describe a
      new strategy to study gene expression and function in cerebellar granule cells.
      In these experiments, we have used square pulse electroporation to introduce
      fluorescent dye or DNA constructs into immature granule cell precursors in situ.
      This method only labels granule cell precursors in the superficial part of the
      external granule layer. Combining this labelling with fluorescent activated cell
      sorting (FACS) allows the transfected cells to be isolated at any time during
      their subsequent development, thus providing a means of analysing granule cells
      as they undergo maturation. This transfection method can be used to study events
      in the normal maturation of granule cells or the effects of introduced
      transgenes. Such studies can be carried out on cells purified from primary
      cultures or cells in situ using cerebellar slice cultures. Our strategy provides
      a new route to detailed analysis of the role of genes in controlling many aspects
      of granule cell biology. These approaches will allow recent global analyses to be
      more readily applied to subpopulations of cells in complex tissues.

PMID- 14706713
TI  - The mapping of the visual field onto the dorso-lateral tectum of the pigeon
      (Columba livia) and its relations with retinal specializations.
AB  - Most of the physiological studies of the pigeon retino-tectal visual pathway have
      investigated the accessible tectum, a small dorso-lateral tectal section that can
      be easily accessed by a simple craniotomy. However, at present we lack a detailed
      study of the topographical arrangement between the visual field, the retina and
      the accessible tectum. In particular, it is not known which section of the visual
      field is mapped onto the accessible tectum, and which of the specialized retinal
      areas mediates this projection. Here we determined, using local field potential
      (LFP) recordings and reverse retinoscopy, the shape, size and position in the
      visual space of the portion of the visual field mapped onto the accessible tectum
      (called here the accessible visual field, or AVF). Using this data and the
      mapping of Nalbach et al. [Vis. Res. 30 (4) (1990) 529], the retinal area
      corresponding to the AVF was determined. Such retinal area was also directly
      delimited by means of retrograde transport of DiI. The results indicate that the
      AVF is a triangular perifoveal zone encompassing only 15% of total visual field.
      The retinal region corresponding to the AVF has the shape of an elongated
      triangle that runs parallel to the visual equator and contains the fovea, the tip
      of the pecten, a perifoveal region of the yellow field and a small crescent of
      the red field. In agreement with this anatomical heterogeneity, visual evoked
      potentials measured in different parts of the accessible tectum present steep
      variations in shape and size. These results are helpful to better design and
      interpret anatomical and physiological experiments involving the pigeon's visual
      system.

PMID- 14706714
TI  - Utilization of an HSV-based amplicon vector encoding the axonal marker hPLAP to
      follow neurite outgrowth in cultured DRG neurons.
AB  - Delivery of genes into DRG neurons by viral vectors is a powerful tool for the
      study of axonal outgrowth. In order to achieve efficient transfer of growth
      related genes and simultaneously label neuronal processes, we have utilized the
      HSV-based amplicon vector system. A bicistronic expression cassette encoding the
      growth associated protein-43 (GAP-43) and the axonal marker human placental
      alkaline phosphatase (hPLAP) reporter gene under translation control of an
      internal ribosomal entry site was cloned into the HGCX amplicon vector. This
      hPLAP reporter enabled efficient labeling of neurites in both dissociated adult
      DRG neurons and embryonic DRG explants. Using this reporter, the effect of GAP-43
      on neurite outgrowth in transduced DRG neurons could be demonstrated. HSV-based
      amplicon vectors can contribute to the study of axonal growth and guidance in
      cultured neurons.

PMID- 14706715
TI  - Dissociated histaminergic neuron cultures from the tuberomammillary nucleus of
      rats: culture methods and ghrelin effects.
AB  - The tuberomammillary nucleus (TMN) in the hypothalamus is the sole source of
      histamine in the brain. This nucleus, by innervating various brain regions, plays
      an important role for vital functions such as arousal and appetite. We have
      developed dissociated primary histaminergic neuron cultures from TMN of postnatal
      (3 and 10-day-old) rats. More than 50% of our cultured neurons from the TMN were
      histaminergic as revealed by adenosine deaminase (AD) as well as histamine
      immunocytochemistry. Among large neurons (diameter, >22 microm), more than 88%
      were histaminergic. Such large neurons (mean diameter, 26.5 microm) were used for
      electrophysiology. Using about 2-month-old TMN cultures, we investigated the
      effects of ghrelin, a recently discovered appetite-stimulating endogenous
      peptide. In GTPgammaS-loaded neurons, ghrelin (3 microM) suppressed currents that
      had previously been activated by an inhibitory neuropeptide, nociceptin. The mean
      current suppression by ghrelin was 471+/-128 pA (S.E.M., n=7). The I-V
      relationship revealed that the ghrelin-suppressed current was inwardly rectifying
      with a reversal potential around E(K). These results suggest that ghrelin
      inhibits G protein-coupled inward rectifier K+ channels (Kir3, GIRK) of TMN
      neurons and that our TMN cultures are useful for investigating physiological
      properties of brain histaminergic neurons.

PMID- 14706716
TI  - Microdialysis of neuropeptide Y in human muscle tissue.
AB  - Microdialysis of neuropeptide Y (NPY) has been reported to be difficult, which
      partly may be due to the adhesive nature of the molecule. The aim of this study
      was to determine the optimal probe and perfusion medium for microdialysis of NPY
      and to investigate if microdialysis can be used to sample NPY from human muscle
      tissue. Three different probe types with a 10mm membrane were used for
      experiments in vitro. They were perfused with a modified Krebs-Henseleit buffer
      (KHB), with or without the addition of 0.5% human serum albumin (HSA). Dialysate
      samples were collected at different flow rates. Ten healthy subjects participated
      in the clinical microdialysis. Microdialysis samples were obtained by probes
      inserted intramuscularly in the right masseter and trapezius muscle and perfused
      with KHB+HSA at a flow-rate of 4 microl/min. The relative recovery of NPY was
      significantly higher in the dialysates with HSA added to the perfusion medium,
      while there was no difference between the three probe types. NPY was detectable
      in 90% of the dialysates from the masseter and in 40% of the dialysates from the
      trapezius muscle. In conclusion, this study shows that NPY can be detected in
      microdialysis samples from human skeletal muscle and that addition of HSA to the
      perfusion medium increases the relative recovery in vitro.

PMID- 14706717
TI  - A perfused rat brain model maintaining the connection between the central and
      peripheral nervous systems.
AB  - We have developed a new perfused brain model in rats. In this model, the cerebral
      circulation is separated from the systemic circulation, while the connections
      between the central and peripheral nervous systems are preserved. After bilateral
      common carotid, external carotid and vertebral artery ligation, bilateral common
      carotid arteries were cannulated to infuse rinsed human type O red blood cells
      mixed with modified Ringer's solution. To drain cerebral venous blood, external
      jugular veins were cannulated. Normal electrocortical activities were observed on
      electroencephalograms (EEGs) for more than 1h after the beginning of the
      perfusion. Somatosensory evoked potentials (SEPs) were also recorded. Direct
      infusion of pentylenetetrazol (PTZ) into the brain induced epileptic discharges
      on the EEGs and active dilation of cerebral arterioles, which was accompanied by
      an increase in systemic blood pressure (BP). The present model, in which we can
      change cerebral blood flow (CBF) and/or cerebral metabolism without directly
      affecting the systemic circulation, will provide a new approach to brain
      research.

PMID- 14706718
TI  - PET Measurement of rCBF in the presence of a neurochemical tracer.
AB  - Functional neurochemical imaging can indicate neurotransmitter release by
      detecting changes in receptor occupancy. A dual tracer positron emission
      tomography (PET) technique is presented here to extend such studies by
      simultaneously measuring changes in regional cerebral blood flow (rCBF). This
      would permit correlations of task or drug induced changes in rCBF and
      neurochemical function. In this proposed method, the rapidly varying signal from
      a blood flow tracer is distinguished from the slowly changing signal due to a
      long-lived neurochemical tracer. As a proof of principle, baseline studies were
      carried out in rhesus monkeys. Two monkeys were anesthetized with isoflurane, and
      [18F]fallypride (t1/2=110 min), a dopamine D2 receptor antagonist, was injected.
      Starting 99-137 min after injection, PET images were acquired every 10 s while
      the blood flow tracer [17F]fluoromethane (t1/2=65 s) was administered by
      inhalation in a repeating pattern of 45 s on/45 s off. The observed time-activity
      curves for 2 ml brain regions were fit with a three compartment lung-body-brain
      model of fluoromethane kinetics with whole brain perfusion fixed. Comparing
      consecutive 6 min scans, reproducibility of relative rCBF and striatal
      [18F]fallypride concentration were 9 and 8%, respectively.

PMID- 14706719
TI  - Depressed mothers coming to primary care: maternal reports of problems with their
      children.
AB  - BACKGROUND: Studies of depressed mothers have generally been conducted in
      psychiatric settings with non-minority, middle-class women. Primary care has an
      increasing role in early detection and treatment, especially for the poor who
      have less access to specialized mental health services. Data on the relationship
      between maternal depression and problems in the offspring in a primary care
      context could help physicians to more effectively identify children in need of
      psychiatric help. METHODS: All mothers aged 25 to 55 from a systematic sample of
      consecutive adults (response rate, 80%) in an urban general medicine practice
      were screened using the PRIME-MD Patient Health Questionnaire (PHQ). Mothers who
      screened positive for major depression (n=85); other psychiatric disorders, but
      not major depression (n=67); or no psychiatric disorders (n=191) were compared on
      their children's history of emotional problems, unmet need for mental health
      treatment, parent-child discord, maternal functional status and mental health
      treatment. RESULTS: Compared to non-psychiatric controls, depressed mothers
      reported a three-times greater risk of serious emotional problems in their
      children (95% confidence interval [CI], 1.7-6.1); a four-times greater risk of
      having their children's problems left untreated (95% CI, 2.3-8.2), and a 10-times
      greater risk of having poor mother-child relations within the past month (95% CI,
      3.9-29.4). Depressed mothers reported more functional disability, more
      psychiatric treatment and more problems in their offspring than mothers with non
      depressive psychiatric disorders. Although a majority of mothers (regardless of
      psychiatric status) believed that counseling (96%) or medication (84%) should be
      offered to those with serious emotional problems, only about half (49%) of the
      depressed mothers had received mental health treatment in the past month.
      LIMITATIONS: Children were not assessed directly. CONCLUSIONS: The children of
      low-income depressed women at a general medicine practice were reported to have a
      greatly increased risk for emotional problems. Many mothers had not received
      treatment for their own emotional problems. By enquiring about the emotional
      health of children of adult primary care patients, primary care providers have an
      opportunity to promote early detection and to facilitate appropriate treatment
      for both the mothers and their children.

PMID- 14706720
TI  - Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with
      anxiety disorders. Results of a multicenter, randomized, placebo-controlled,
      double-blind clinical trial.
AB  - BACKGROUND: The aim of the present trial was to investigate the efficacy and
      safety of kava special extract WS 1490 in patients with sleep disturbances
      associated with anxiety, tension and restlessness states of non-psychotic origin.
      METHODS: In a multicenter, randomized, double-blind clinical study, 61 patients
      received daily doses of 200 mg WS 1490 or placebo over a period of 4 weeks.
      Efficacy was measured by the sleep questionnaire SF-B, the Hamilton Anxiety Scale
      (HAMA), the Bf-S self-rating scale of well-being and the Clinical Global
      Impressions (CGI) scale. RESULTS: The confirmatory analysis of the two primary
      efficacy variables, the differences of sleep questionnaire SF-B sub-scores
      'Quality of sleep' and 'Recuperative effect after sleep' after 4 weeks of double
      blind treatment compared to baseline, demonstrated statistically significant
      group differences in favor of kava extract WS 1490 (P=0.007 and P=0.018,
      respectively). Superior effects of kava extract were also present in the HAMA
      psychic anxiety sub-score (P=0.002). More pronounced effects with respect to the
      self-rating of well-being and the global clinical evaluation also indicated
      superior therapeutic efficacy of kava extract. Safety and tolerability were good,
      with no drug-related adverse events or changes in clinical or laboratory
      parameters. CONCLUSIONS: We conclude that sleep disturbances associated with non
      psychotic anxiety disorders can be effectively and safely treated with kava
      extract WS 1490.

PMID- 14706721
TI  - Seasonal variation in postnatal depression.
AB  - BACKGROUND: We evaluated the occurrence of postnatal depression in general and
      during different seasons as part of a larger longitudinal mother-child follow-up
      study. METHOD: One hundred and eighty-five mothers, from the maternity wards of
      University Hospital of Oulu, Finland, completed a self-rating depression scale,
      the Edinburgh Postnatal Depression Scale (EPDS) twice: first at hospital 2-7 days
      after delivery and the second time at home 4 months after the delivery. Different
      psychosocial variables were mapped out to avoid any confounding factors. The year
      was divided in two separate ways: first, three different time periods were
      selected by the amount of sunlight: dark (October-January), intermediate
      (February, March, August, September) and light (April-July), and second, the year
      was divided by seasons. The results were analysed by the chi(2)-test for
      multinomials. RESULTS: Sixteen percent (16.2) of mothers were scored as being
      depressed using 13 as a cut-off point immediately after the infant was born.
      Thirteen percent (13.0) were depressed measured 4 months postpartum. There was
      more mild depression in the autumn (ratio observed/expected 1,62; 95% confidence
      interval 1.05-2.19) immediately after delivery, using 10 as a cut-off, and less
      depression in the spring (0.27; 0.00-0.62) measured at home later, using 13 as a
      cut-off. When using classification by the amount of light there was more
      depression during the dark time (1.58; 1.05-2.11) immediately postpartum.
      LIMITATIONS: The group sizes and the amount of sample sizes collected within each
      month are quite small. CONCLUSIONS: It should be borne in mind that seasonal
      changes and alterations in the amount of light might influence the occurrence of
      postnatal depression.

PMID- 14706722
TI  - Valence-related vigilance biases in anxiety studied through event-related
      potentials.
AB  - INTRODUCTION: Behavioral experiments on reaction time indicate that anxious
      subjects' vigilance-related attention is biased towards threatening words, though
      direct data on cerebral activity associated to this bias are conspicuously
      scarce. METHODS: In the present study, event-related potentials (ERPs) were
      recorded from 30 subjects, grouped according to their scores in trait and state
      anxiety questionnaires. The specific role of the arousal and valence content of
      the stimulation in the vigilance bias was investigated by blocking the arousal
      content. Stimulation with high biological significance was employed. An S1
      (sound)-S2 (emotional picture) task ensured that subjects were vigilant towards
      positive, negative or control (neutral) images. RESULTS: Only subjects presenting
      high state scores and high state-trait combination scores showed significantly
      higher amplitudes in the Early Contingent Negative Variation during vigilance
      towards negative stimuli. This ERP component typically appears between S1 and S2
      and reflects the intensity of vigilance. CONCLUSIONS: ERP activity detects
      cerebral indices that confirm the presence of valence-related vigilance biases in
      anxiety.

PMID- 14706723
TI  - Comparative validity of three screening questionnaires for DSM-IV depressive
      disorders and physicians' diagnoses.
AB  - BACKGROUND: The aim of this study was to compare the validity of the Hospital
      Anxiety and Depression Scale (HADS), the WHO (five) Well Being Index (WBI-5), the
      Patient Health Questionnaire (PHQ), and physicians' recognition of depressive
      disorders, and to recommend specific cut-off points for clinical decision making.
      METHODS: A total of 501 outpatients completed each of the three depression
      screening questionnaires and received the Structured Clinical Interview for DSM
      IV (SCID) as the criterion standard. In addition, treating physicians were asked
      to give their psychiatric diagnoses. Criterion validity and Receiver Operating
      Characteristics (ROC) were determined. Areas under the curves (AUCs) were
      compared statistically. RESULTS: All depression scales showed excellent internal
      consistencies (Cronbach's alpha: 0.85-0.90). For 'major depressive disorder', the
      operating characteristics of the PHQ were significantly superior to both the HADS
      and the WBI-5. For 'any depressive disorder', the PHQ showed again the best
      operating characteristics but the overall difference did not reach statistical
      significance at the 5% level. Cut-off points that can be recommended for the
      screening of 'major depressive disorder' had sensitivities of 98% (PHQ), 94% (WBI
      5), and 85% (HADS). Corresponding specificities were 80% (PHQ), 78% (WBI-5), and
      76% (HADS). In contrast, physicians' recognition of 'major depressive disorder'
      was poor (sensitivity, 40%; specificity, 87%). LIMITATIONS: Our sample may not be
      representative of medical outpatients, but sensitivity and specificity are
      independent of disorder prevalence. CONCLUSIONS: All three questionnaires
      performed well in depression screening, but significant differences in criterion
      validity existed. These results may be helpful in the selection of questionnaires
      and cut-off points.

PMID- 14706724
TI  - Five-minute recordings of heart rate variability in obsessive-compulsive
      disorder, panic disorder and healthy volunteers.
AB  - BACKGROUND: Recent studies have used spectral analysis of heart rate variability
      (HRV) to study autonomous nervous system (ANS) function in panic disorder (PD).
      Most studies reported a reduced HRV in resting PD patients, suggesting increased
      sympathetic and decreased parasympathetic tone. In obsessive-compulsive disorder
      (OCD) inconsistent findings have been reported on ANS function and to date no
      studies have been carried out with spectral analysis of HRV. In this HRV study we
      compared ANS function in patients with PD, OCD and normal controls. METHODS:
      Standardized HRV measurement was carried out in 24 PD patients, 26 OCD patients
      and 24 age-matched normal controls. All patients were drug free. As this
      comparison yielded unexpected results, the PD and normal control samples were
      enlarged to 53 and 54 subjects, respectively, to verify our first measurement.
      RESULTS: OCD patients were not characterized by a reduced HRV, as compared to
      normal controls. This was also found in PD patients, even in the enlarged sample.
      CONCLUSIONS: HRV analysis in patients with OCD or PD showed that these patients
      were not characterized by ANS abnormalities, as no evidence was found of
      diminished HRV in a large sample of resting OCD and PD patients, measured sitting
      on a hospital bed.

PMID- 14706725
TI  - Mixed depressive features predict maniform switch during treatment of depression
      in bipolar I disorder.
AB  - BACKGROUND: Case observations imply that depressed patients with mixed features
      are of high risk for maniform switch during acute treatment. METHODS: The medical
      records of 158 bipolar I depressives were examined with respect to mixed
      depressive features at admission, naturalistic medications, and maniform switch
      during inpatient treatment. RESULTS: Besides pharmacological variables, the
      number of mixed depressive symptoms (flight of ideas, racing thoughts, logorrhea,
      aggression, excessive social contact, increased drive, irritability, and
      distractibility) at admission was associated with a higher risk for, and the
      acceleration of, maniform switch during inpatient treatment. LIMITATIONS: This
      was a retrospective study in patients receiving naturalistic treatment. The
      cohort was hospital based and thus not representative of the full range of
      bipolar affective disorder. CONCLUSIONS: In line with recent studies, our results
      underline the factors inherent in subjects at a higher risk of switch.
      Investigation of the relationships between several inherent factors and their
      interactions with pharmacological treatments may be important in resolving the
      controversy surrounding antidepressant-induced mania. Further validation studies
      on mixed depression are warranted.

PMID- 14706727
TI  - Rates of study completion with single versus split daily dosing of
      antidepressants: a meta-analysis.
AB  - OBJECTIVE: To examine the tolerability of single versus multiple daily dosing
      (SDD vs. MDD) of antidepressant drugs in clinical practice. METHOD: Studies
      comparing single versus multiple daily dosing of antidepressants were reviewed.
      Since there were no numeric data available on the rates of adverse events for the
      SDD versus MDD arms, meta-analyses were carried out to compare rates of study
      completers (or rates of drop-outs) with single versus multiple daily dosing.
      RESULTS: The review process identified 22 studies meeting our inclusion criteria.
      This meta-analysis found no difference in the rates of study completers with SDD
      or MDD regime of antidepressants. CONCLUSION: Our analysis on rates of completers
      (or rates of drop-outs) gives us an estimation of the overall acceptability of
      treatment and of course, but has limited utility when compared to the rates of
      adverse events. Yet, the present analyses suggest that adverse events which are
      significant enough to result in drop-outs, are not more frequent with SDD than
      MDD. MDD strategy of antidepressants does not seem to be more advantageous for
      the acceptability of treatment and obviously is disadvantageous for compliance.
      Thus, a simplified treatment regimen may be practical to increase treatment
      success rates in depression.

PMID- 14706726
TI  - The effect of bright light exposure on pupillary fluctuations in healthy
      subjects.
AB  - BACKGROUND: Light therapy is thought to be the first choice treatment of winter
      depression. However, its way of action is poorly understood. In order to find a
      solid effect of bright artificial light, we studied its possible alerting action
      through the spontaneous fluctuations of the pupil, considered to be an objective
      measurement of vigilance. METHODS: Pupillary fluctuations of 10 healthy subjects
      (mean age: 22+/-1 S.D. years) were measured for 60 s before and 15 min after 0.5
      h, 10000-lux light exposure. The cumulative change in pupil size, characterised
      by the pupillary unrest index (PUI) decreased at each subject, and this decrease
      was in average 35+/-4.4% S.E.M. The average pupillary diameters were unchanged
      (101+/-2.2% S.E.M.). This analysis revealed that the slow components of the
      pupillary fluctuations also decreased considerably. LIMITATIONS: There was no dim
      light or other placebo control of the light treatment. CONCLUSIONS: Bright light
      exposure significantly influenced the pupillary fluctuations. We suppose that
      bright light exposure increases the level of alertness, and this could be a
      possible way by which bright artificial light exerts a beneficial effect also in
      affective disorders.

PMID- 14706728
TI  - Can we identify mothers at risk for postpartum depression in the immediate
      postpartum period using the Edinburgh Postnatal Depression Scale?
AB  - BACKGROUND: Postpartum depression is a major health issue for many women around
      the world with well-documented negative health consequences for the mother, child
      and family. While research has demonstrated the amenability of postpartum
      depression to treatment, there is preliminary evidence suggesting maternal mood
      in the immediate postpartum period may be predictive of postpartum depression
      such that secondary preventive interventions may be implemented. METHODS: A
      population-based sample of 594 mothers completed the Edinburgh Postnatal
      Depression Scale (EPDS) at 1, 4 and 8 weeks postpartum. The sensitivity,
      specificity and predictive power of the 1-week EPDS in relation to identifying
      mothers with elevated EPDS scores at 4 and 8 weeks was determined. The predictive
      power of the 1-week EPDS was further assessed using odds ratios and receiver
      operator characteristic (ROC) curves. RESULTS: At 1 week postpartum, 29.5% of
      mothers scored >9 on the EPDS, decreasing to 23% at 4 weeks and 20.5% at 8 weeks.
      Using the cut-off score of 9/10, the 1-week EPDS accurately classified 85.4%
      mothers at 4 weeks and 82.5% mothers at 8 weeks with or without postpartum
      depression symptomatology. The 1-week EPDS was significantly correlated to the 4
      week (r=0.72, P<0.001) and 8-week (r=0.65, P<0.001) EPDS. Mothers with a 1-week
      EPDS score >9 were 30.3 times more likely at 4 weeks (95% CI=17.5-42.3) and 19.1
      times more likely at 8 weeks (95% CI=11.0-32.9) to exhibit postpartum depression
      symptomatology. LIMITATIONS: Psychiatric interviews were not completed in
      collaboration with the EPDS. CONCLUSION: The EPDS administered in the 1st week
      postpartum was predictive of maternal mood at 4 and 8 weeks postpartum. To
      identify mothers at high risk for postpartum depression, health care
      professionals could consider screening all new mothers in the immediate
      postpartum period such that secondary preventive interventions may be
      implemented.

PMID- 14706729
TI  - Adjunctive therapy versus alternative monotherapy in patients with partial
      epilepsy failing on a single drug: a multicentre, randomised, pragmatic
      controlled trial.
AB  - OBJECTIVE: To evaluate the value of alternative monotherapy versus adjunctive
      therapy in partial epilepsy refractory to single antiepileptic drug (AED)
      therapy. DESIGN AND METHODS: In a multicentre, parallel-group, open-label study,
      patients with cryptogenic or symptomatic partial epilepsy not controlled after
      single or sequential AED monotherapies were randomised to monotherapy with an
      alternative AED or to adjunctive therapy with a second AED. The AED to be
      added/substituted and dose adjustments were determined by the physician's best
      judgement. Patients were followed up until withdrawal from the allocated
      treatment or for 12 months, whichever first. Outcome measures included proportion
      of patients continuing on the assigned treatment strategy, proportion of patients
      seizure-free after achieving the target maintenance dose, and adverse effects
      rates. Data were analysed by actuarial life tables, Kaplan-Meier survival
      analysis and Cox proportional hazard regression model. RESULTS: Of a total of 157
      patients (including 94 previously exposed to only one AED), 76 were randomised to
      alternative monotherapy and 81 to adjunctive therapy. The two groups were
      balanced in clinical characteristics. The 12-month cumulative probability of
      remaining on the assigned treatment was 55% in patients randomised to alternative
      monotherapy and 65% in those randomised to adjunctive therapy (P=0.74). The 12
      month probability of remaining seizure-free was 14 and 16%, respectively
      (P=0.74). Adverse effects were similar in the two groups. No significant
      differences in outcome within or between groups were identified based on etiology
      of epilepsy and previous AED exposure. CONCLUSIONS: Although these findings
      should be interpreted with caution due to the low statistical power resulting
      from the relatively small sample size, alternative monotherapy and adjunctive
      therapy were associated with similar outcomes. Further work is required to
      determine whether outcome could be improved through identification of specific
      AED combinations with synergistic activity.

PMID- 14706730
TI  - Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit
      expression patterns after kainate-induced status epilepticus in aging rats.
AB  - Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive
      status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging
      related differences in the effect of prolonged SE on the expression of
      hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was
      performed on hippocampal sections using antibodies directed against the alpha1
      subunit of class A-D VGCCs. Compared to age-matched controls, SE animals showed a
      marked loss of alpha1A immunoreactivity (IR) in CA3 and the hilus, which was more
      prominent in aged animals. Alpha1B-IR was decreased selectively in the stratum
      lucidum of CA3. Alpha1C-IR was increased on neuronal somata in the pyramidal and
      granule cell layers of both age groups. In contrast, there was a marked decrease
      of alpha1C-IR in the neuropil of CA3 stratum pyramidale and portions of CA1,
      which was more pronounced in aged animals. Alpha1D-IR was decreased in CA3 and
      the hilus, which was more prominent in aged animals. Nissl staining demonstrated
      mild somal dysmorphia in the pyramidal cell layer of CA3, which was more apparent
      in aged animals. Fluoro-Jade B staining was prominent in the stratum pyramidale
      of CA3 and in the hilus of aged SE animals. These results demonstrated that
      expression patterns of hippocampal high-threshold VGCC alpha1 subunits were
      altered variably during prolonged convulsive SE and were associated with
      prominent early degenerative changes in aged neurons in CA3 and the hilus.

PMID- 14706731
TI  - Partial hippocampal kindling increases GABAB receptor-mediated postsynaptic
      currents in CA1 pyramidal cells.
AB  - In previous studies, we showed that partial hippocampal kindling decreased the
      efficacy of the presynaptic GABAB receptors on both GABAergic and glutamatergic
      terminals of CA1 neurons in hippocampal slices in vitro. In this study, GABAB
      receptor-mediated inhibitory postsynaptic currents (GABAB-IPSCs) were assessed by
      whole-cell recordings in CA1 pyramidal neurons in hippocampal slices of male Long
      Evans rats. The peak GABAB-IPSC evoked by a brief train of supramaximal stratum
      radiatum stimuli (20 pulses of 300 Hz) in the presence of picrotoxin (0.1 mM) and
      kynurenic acid (1 mM) was larger in neurons of kindled (65.9 +/- 5.2 pA, N=42
      cells) than control (45.8 +/- 4.8 pA, N=32 cells) rats (P<0.01). Adding GABA
      uptake blocker nipecotic acid (1 mM) or GABAB receptor agonist baclofen (0.01 mM)
      in the perfusate induced outward currents that were blocked by GABAB receptor
      antagonist CGP 55845A (1 microM). The peak outward current induced by nipecotic
      acid was larger in neurons of the kindled (55.4 +/- 5.7 pA, N=30) than the
      control group (39.8 +/- 4.5 pA, N=28) (P<0.05). However, the magnitude of the
      baclofen-induced current was not different between kindled (90.8 +/- 6.9 pA,
      N=29) and control (87.2 +/- 5.9 pA, N=21) groups (P>0.05). We concluded that
      partial hippocampal kindling increased GABAB-IPSCs in hippocampal CA1 pyramidal
      cells via multiple presynaptic mechanisms.

PMID- 14706732
TI  - Levels of the synaptic protein X11 alpha/mint1 are increased in hippocampus of
      rats with epilepsy.
AB  - X11 alpha or Mint1 is a protein containing an N-terminal sequence, which binds to
      Munc-18 protein, a middle phosphotyrosine-binding domain (PTB) and two C-terminal
      PDZ (Post-synaptic density/Discs large/Zone Occludens-1) domains. The PDZ
      domains, which mediate protein-protein interactions have been shown to be
      involved in the organization of synaptic signaling pathways. Mint1 plays an
      important role in vesicle synaptic transport toward the active zone at the pre
      synaptic site, and also participates in the transport of NR2B subunit of the NMDA
      receptor, to the post-synaptic site. To investigate the participation and
      distribution of this protein in the hippocampal subfield of rats submitted to the
      pilocarpine model of epilepsy, Mint1 was analyzed using Western blotting and
      immunohistochemistry. Animals of 5 h of status epilepticus showed decreased
      levels of this protein in the hippocampus when compared to the control animals.
      In contrast, animals from seizure-free period (silent group) and during
      spontaneous seizures phase (chronic group) showed increased Mint1 immunostaining
      in all hippocampal subfields, mainly in the dentate gyrus, when compared to the
      control group. The blotting confirmed the results obtained by
      immunohistochemistry. The present work suggests that Mint1 may be related to
      hippocampal plasticity during epileptogenesis in the pilocarpine model of
      temporal lobe epilepsy.

PMID- 14706733
TI  - The diagnosis of epileptic and non-epileptic seizures.
AB  - The aim of this prospective population-based study was to systematically define a
      cluster of diagnostic items which can assist in the early identification and
      classification of epileptic and non-epileptic seizures. A cohort of patients aged
      > or =14 years, suspected with a first epileptic seizure, were included in this
      study. A team of neurologists evaluated and classified all cases. Diagnostic
      items for epileptic and non-epileptic seizures were identified using logistic
      regression analysis. Three hundred and fifty cases entered this study.
      Distinctive features for epileptic seizures were postictal confusion (OR 0.09),
      an epileptiform EEG pattern (OR 0.02), and abnormal neuroimaging findings (OR
      0.07), whereas for non-epileptic seizures of organic origin there was a history
      of hypertension (OR 7.5), and provoking factors (OR 13.4) such as exercise and
      warmth. Diagnostic items for seizures of non-organic origin were a history of
      febrile seizures (OR 5.8), treatment by a psychologist or psychiatrist (OR 9.1),
      and presentiment of the seizure (OR 3.7) such as a feeling of choking and
      palpitations. A separate analysis for the patients who were systematically
      investigated provided some additional diagnostic items for the different
      subgroups of patients. For instance, back arching during the seizure for the
      patients with seizures of non-organic origin and female sex for the patients with
      non-epileptic seizures of organic origin.

PMID- 14706734
TI  - Carbamazepine affects autonomic cardiac control in patients with newly diagnosed
      epilepsy.
AB  - Previous studies indicate that epilepsy patients may have impaired autonomic
      cardiovascular control in the interictal state although it is unclear whether the
      observed reduction in cardiovascular responses is due to the epilepsy and the
      interictal epileptogenic discharges, or to the treatment with antiepileptic
      drugs. Spectral analysis of heart rate variability makes it possible to partly
      separate the sympathetic components, low frequency (LF), from the vagal
      components, high frequency (HF) of autonomic cardiac control. We used spectral
      analysis of heart rate variability to assess the effect of carbamazepine (CBZ) on
      autonomic cardiac control in patients with newly diagnosed epilepsy. Fifteen
      adult outpatients with newly diagnosed seizures/epilepsy underwent 24 h
      ambulatory EKG recordings before and after commencement of CBZ treatment. Total
      power as well as low frequency (LF), very low frequency (VLF) and high frequency
      (HF) power in heart rate variability was calculated. When analysing the full 24 h
      recordings, patients had significantly lower standard deviation of RR-intervals
      (P=0.0015), total power (P=0.0010), LF (P=0.0002), VLF (P=0.0025) and HF
      (P=0.0139) during treatment with CBZ than before. The results were very similar
      for daytime and night time recordings. Our observations demonstrate that CBZ may
      suppress both parasympathetic and sympathetic functions in newly diagnosed
      patients with epilepsy. The possible implications of our results for sudden
      unexpected death in epilepsy are discussed.

PMID- 14706735
TI  - Calorie restriction may not elevate the threshold of PTZ-induced seizures.

PMID- 14706737
TI  - Lipid bilayers: thermodynamics, structure, fluctuations, and interactions.
AB  - This article, adapted from our acceptance speech of the Avanti Award in Lipids at
      the 47th Biophysical Society meeting in San Antonio, 2003, summarizes over 30
      years of research in the area of lipid bilayers. Beginning with a theoretical
      model of the phase transition (J.F.N.), we have proceeded experimentally using
      dilatometry and density centrifugation to study volume, differential scanning
      calorimetry to study heat capacity, and X-ray scattering techniques to study
      structure of lipid bilayers as a function of temperature. Electron density
      profiles of the gel and ripple phases have been obtained as well as profiles from
      several fluid phase lipids, which lead to many structural results that compliment
      molecular dynamics simulations from other groups. Using the theory of liquid
      crystallography plus oriented lipid samples, we are the first group to obtain
      both material parameters (KC and B) associated with the fluctuations in fluid
      phase lipids. This allows us to use fully hydrated lipid samples, as in vivo, to
      obtain the structure.

PMID- 14706738
TI  - Can cholesterol absorption be reduced by phytosterols and phytostanols via a
      cocrystallization mechanism?
AB  - The formation of mixed water-insoluble poorly absorbable crystals between
      cholesterol (CH) and phytosterols (PS) or phytostanols (PSS) in the intestinal
      lumen has been considered for a long time as a plausible mechanism of the PS/PSS
      induced reduction of serum CH concentration. In this report, we demonstrated with
      the use of the powder X-ray diffraction (XRD) and the differential scanning
      calorimetry (DSC) techniques that mixed CH:beta-sitosterol (SI) crystals can be
      formed by recrystallization of corresponding mixtures from melts and also from
      mixed CH:SI solutions in triglyceride oil. Formation of mixed CH:SI crystals
      takes place in a wide interval of CH:SI ratios, from approximately 10 up to
      approximately 75 wt.% of SI in the mixture. Formation of mixed CH:sitostanol (SS)
      crystals from melts and solutions in triglyceride oil was also detected, but in a
      more narrow interval of CH:SS ratios. However, during the lipolysis of model
      dietary emulsions under in vitro conditions, the formation of crystalline
      material was not detected due to the relatively high solubility of free
      sterols/stanols in products of fat hydrolysis. We found that the solubility of
      free CH, SI, and SS raises upon the increase in the solvent polarity, i.e. free
      fatty acid > diglycerideoil > triglyceride oil. Therefore, we believe that the
      cocrystallization mechanism of phytosterol-induced serum CH lowering has
      relatively low importance, unless the diet is specially designed to include
      relatively little amounts of dietary fats. The presented experimental evidence
      demonstrates that it is unlikely that the formation of poorly absorbable mixed
      crystals largely affects the intestinal absorption of CH and, therefore, that
      this is a prime mechanism by which PS and PSS effect CH absorption.

PMID- 14706739
TI  - Synthesis and properties of methyl 5-(1'R,2'S)-(2-octadecylcycloprop-1
      yl)pentanoate and other omega-19 chiral cyclopropane fatty acids and esters
      related to mycobacterial mycolic acids.
AB  - A 23-26-carbon chain length range of omega-19 (1'R,2'S) cyclopropane fatty acids,
      related to mycobacterial mycolic acids, has been prepared. The key cyclopropyl
      intermediate, (1'R,2'S)-(Z)-1-formyl-2-octadecylcyclopropane, underwent Wittig
      chemistry with various reagents to provide vinylic precursors, which were
      selectively reduced to the corresponding saturated omega-19 cyclopropane fatty
      acids or esters. The 24-carbon omega-19 cyclopropane ester was made by chain
      elongation of the 23-carbon ester. Saturated and unsaturated chiral cyclopropane
      acids and esters were assayed, using wall extracts of Mycobacterium smegmatis;
      the incorporation of 14C-acetate was used to measure inhibition or stimulation of
      mycolic acid synthesis. Minor inhibition (2-3%) was shown by the 23- and 24
      carbon saturated esters; all the other compounds were stimulants. The most
      effective (38-55%) stimulators of mycolate synthesis were the unsaturated esters
      with 23- and 26-carbons and the saturated and unsaturated 25-carbon acids.

PMID- 14706740
TI  - Thermotropic and lyotropic properties of long chain alkyl glycopyranosides: part
      III: pH-sensitive headgroups.
AB  - As part of a series of papers, the influence of carbohydrate headgroups and
      aliphatic chains on the mesogenic properties of glycolipids was investigated.
      Alkyl glycosides with different types of aliphatic chains were synthesised.
      Neutral glycolipids were oxidized to their uronic acid derivatives, using the
      well established TEMPO-oxidation. For comparison a 6-deoxy-6-amino
      alkylglucopyranoside was synthesised. In addition, the thermotropic and lyotropic
      phase behaviour of the synthesised compounds were investigated. The thermotropism
      was characterised by polarising microscopy, the lyotropism by the contact
      preparation method.

PMID- 14706741
TI  - Alkylglucosides with isoprenoid-type hydrophobic chains-effects of hydrophobic
      chain size on the aqueous phase behavior.
AB  - Aqueous phase diagrams were constructed for two new alkylglucosides with
      isoprenoid-type hydrophobic chains, viz. 1-O-beta-(3,7-dimethyloctyl)-D
      glucopyranoside, beta-Glc(Ger), and 1-O-beta-(3,7,11,15-tetramethylhexadecyl)-D
      glucopyranoside, beta-Glc(Phyt). In a low concentration regime, from 0.17 to 34
      wt.% beta-Glc(Ger), the beta-Glc(Ger)/water system exhibits two phase, a dilute
      (L1dil) and a concentrated isotropic phase (L1con), coexistence region. Above
      about 62 wt.% beta-Glc(Ger), an Lalpha phase is formed. The extent of the L1dil +
      L1conc two-phase region decreases as temperature increases and totally disappears
      above 130 degrees C, exhibiting an upper critical temperature. The beta
      Glc(Phyt)/water system exhibits an Lalpha phase above 78 wt.% surfactant below
      which, an Lalpha + water two-phase region appears. One notable feature of these
      compounds is their low values of Krafft-eutectic temperature, TK, e.g. the value
      of TK for beta-Glc(Phyt) is below 0 degrees C although the total number of carbon
      atoms in the hydrophobic chain is as large as 20.

PMID- 14706742
TI  - Incorporation of beta-lactoglobulin in a lipid/porphyrin monolayer at the air-
      water interface.
AB  - A catanionic lipid/porphyrin monolayer was formed at the air-water interface by
      the tetra-anionic porphyrin, tetra-sodium-meso-tetra(4-sulfonatophenyl)porphine
      (TSPP), mixed with the cationic lipid dioctadecyldimethylammonium bromide (DODAB)
      in a 1:4 molar ratio. This binary mixture (TSPP/4DODAB) was used as the
      incorporation matrix of beta-lactoglobulin (betaLG). Binary and ternary systems
      (TSPP/4DODAB/zbetaLG, where z stands for the number of protein residues per TSPP)
      were characterized by surface pressure versus area (pi-A) measurements and by
      Brewster angle microscopy (BAM) observation at the air-water interface. Pi-A
      measurements and BAM images show that protein is incorporated in the expanded
      regime of the monolayer and is gradually expelled upon compression at high
      surface pressures. The successive compression-expansion cycles indicate that the
      protein under adsorbed to the floating film is reincorporated after the expansion
      of the monolayer. At low subphase pH, TSPP tends to aggregate decreasing the
      interaction with DODAB molecules. Electrostatic and hydrophobic interactions are
      responsible for the presence of betaLG at the interfacial film.

PMID- 14706743
TI  - Organization and dynamics of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-labeled
      lipids: a fluorescence approach.
AB  - Lipids that are labeled with the NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) group
      are widely used as fluorescent analogues of native lipids in biological and model
      membranes to monitor a variety of processes. NBD-labeled lipids have previously
      been used to monitor the organization and dynamics of molecular assemblies such
      as membranes, micelles and reverse micelles utilizing the wavelength-selective
      fluorescence approach. In this paper, we have characterized the organization and
      dynamics of various NBD-labeled lipids using red edge excitation shift (REES) and
      other fluorescence approaches which include analysis of membrane penetration
      depths of the NBD group using the parallax method. We show here that the
      environment and location experienced by the NBD group of the NBD-labeled lipids
      could depend on the ionization state of the lipid. This could have potentially
      important implications in future studies involving NBD-labeled lipids as tracers
      in a cellular context.

PMID- 14706744
TI  - The effect of increasing concentrations of precipitating salts used to
      crystallize proteins on the structure of the lipidic Q224 cubic phase.
AB  - A major obstacle to elucidating the structure of membrane proteins at high
      resolution is the difficulty of preparing these proteins as well as to grow well
      ordered crystals. During the last few years several groups have considered the
      use of three-dimensional bicontinuous lipidic cubic phases as a possible
      crystallization matrix for such molecules. In a few cases these studies have been
      successfully approached by other laboratories, however, a number of questions
      remain, particularly in regard to the effects of solutes on the phase diagrams of
      lipid-water systems. In the present work we report the structural behavior of the
      lipidic Q224 (Pn3m), Q230 (Ia3d) and HII phases systematically studied in the
      presence of a range of concentrations of various salts and precipitating agents
      at various pH values. Some of the results reported here have been presented
      elsewhere Vargas et al. (2000) [Strategies in membrane protein crystallization.
      Chemical Prospectives in Crystallography of Molecular Biology. International
      School of Crystallography, NATO-ASI course, Erice (Italy)].

PMID- 14706745
TI  - Determination of liposomal encapsulation efficiency using proton NMR
      spectroscopy.
AB  - A rapid and simple approach using 1H NMR was developed for determination of
      liposomal encapsulation efficiency without the need for physical separation of
      entrapped and non-entrapped marker. Measurements were made using a marker
      (homocarnosine) with a pH-sensitive 1H chemical shift in the presence of a pH
      gradient across the phospholipid vesicle membrane, or by addition of the chemical
      shift reagent, thulium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra
      (methylene phosphonic acid sodium salt) (TmDOTP5-). The measured encapsulation
      efficiencies for the liposomal dispersions prepared from 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) through extrusion using 50, 200 and 1000 nm
      polycarbonate membranes were found to be identical using the two different
      experimental approaches.

PMID- 14706746
TI  - Real-time reverse transcription PCR analysis of expression of atrazine catabolism
      genes in two bacterial strains isolated from soil.
AB  - The level of expression of highly conserved, plasmid-borne, and widely dispersed
      atrazine catabolic genes (atz) was studied by RT-qPCR in two telluric atrazine
      degrading microbes. RT-qPCR assays, based on the use of real-time PCR, were
      developed in order to quantify atzABCDEF mRNAs in Pseudomonas sp. ADP and atzABC
      mRNAs in Chelatobacter heintzii. atz gene expression was expressed as mRNA copy
      number per 10(6) 16S rRNA. In Pseudomonas sp. ADP, atz genes were basally
      expressed. It confirmed atrazine-degrading kinetics indicating that catabolic
      activity starts immediately after adding the herbicide. atz gene expression
      increased transitorily in response to atrazine treatment. This increase was only
      observed while low amount of atrazine remained in the medium. In C. heintzii,
      only atzA was basally expressed. atzA and atzB expression levels were similarly
      and significantly increased in response to atrazine treatment. atzC was not
      expressed even in the presence of high amounts of atrazine. This study showed
      that atz genes are basally expressed and up-regulated in response to atrazine
      treatment. atz gene expression patterns are different in Pseudomonas ADP and C.
      heintzii suggesting that the host may influence the expression of plasmid-borne
      atrazine-catabolic potential.

PMID- 14706747
TI  - Molecular profiling of microbial communities associated with seeds of Beta
      vulgaris subsp. Vulgaris (sugar beet).
AB  - The composition of microbial communities on and within seeds may effect their
      storage and field performance, whether they are indigenous or applied as
      biocontrol agents. In this study, we have explored the usefulness of profiling
      small subunit ribosomal (SSR) gene fragments for studying the microflora
      associated with seeds. DNA was amplified by the polymerase chain reaction (PCR)
      and the amplicons separated using denaturing gradient gel electrophoresis (DGGE).
      Primers targeting eukaryotic SSRs were used to investigate fungal communities,
      and primers targeting bacterial SSRs were employed to study the eubacterial
      microflora. As a case study, we attempted to profile the fungi and bacteria
      associated with seeds of Beta vulgaris (sugar beet) to permit an insight into the
      varying field performance of several well-characterised commercial seed lots.
      Serious interference with the microbial signals was observed from the plant's own
      nuclear 18S rRNA genes and chloroplast 16S rRNA genes using standard PCR
      conditions and DNA extracted from whole seeds as template. Hot-start and
      touchdown PCR made no appreciable improvement to these signals. Seed imbibition
      and dissection into operculum and fruit wall and true seed prior to DNA
      extraction improved signal recovery in the fruit fraction. With primer
      modification, bacteria and fungi were detected in an excess of plant DNA of 100:1
      and 10:1, respectively. With this method, microbial communities on seeds could be
      profiled, however, it is likely that targeted depletion of plant rDNA targets
      will be a necessary extra step before this approach can be used to screen seeds
      routinely.

PMID- 14706748
TI  - An improved method of microencapsulation and its evaluation to protect
      Lactobacillus spp. in simulated gastric conditions.
AB  - An improved method of microencapsulation was developed to increase the efficacy
      of capsules in protecting the encapsulated bacteria under simulated gastric
      conditions. Lactobacillus acidophilus CSCC 2400 was encapsulated in calcium
      alginate and tested for its survival in simulated gastric conditions. The effects
      of different capsule sizes (200, 450, 1000 microm), different sodium alginate
      concentrations (0.75%, 1%, 1.5%, 1.8% and 2% w/v) and different concentrations of
      calcium chloride (0.1, 0.2, 1.0 M) on the viability of encapsulated bacteria were
      investigated. The viability of the cells in the microcapsules increased with an
      increase in alginate capsule size and gel concentration. There was no significant
      difference (p>0.05) in the viability of encapsulated cells when the concentration
      of calcium chloride was increased. Increase in cell load during encapsulation
      increased the number of bacterial survivors at the end of 3-h incubation in
      simulated gastric conditions. Hardening the capsule in calcium chloride solution
      for a longer time (8 h) had no impact on increasing the viability of encapsulated
      bacteria in a simulated gastric environment. The release of encapsulated cells at
      different phosphate buffer concentrations was also studied. When encapsulated L.
      acidophilus CSCC 2400 and L. acidophilus CSCC 2409 were subjected to low pH (pH
      2) and high bile concentration (1.0% bile) under optimal encapsulation conditions
      (1.8% (w/v) alginate, 10(9) CFU/ml, 30 min hardening in 0.1 M CaCl(2) and capsule
      size 450 microm), there was a significant increase (p<0.05) in viable cell
      counts, compared to the free cells under similar conditions. Thus the
      encapsulation method described in this study may be effectively used to protect
      the lactobacillus from adverse gastric conditions.

PMID- 14706749
TI  - Multiplex FISH analysis of a six-species bacterial biofilm.
AB  - Established procedures use different and seemingly incompatible experimental
      protocols for fluorescent in situ hybridization (FISH) with Gram-negative and
      Gram-positive bacteria. The aim of this study was to develop a procedure, based
      on FISH and confocal laser scanning microscopy (CLSM), for the analysis of the
      spatial organization of in vitro biofilms containing both Gram-negative and Gram
      positive oral bacteria. Biofilms composed of the six oral species Actinomyces
      naeslundii, Candida albicans, Fusobacterium nucleatum, Streptococcus oralis,
      Streptococcus sobrinus, and Veillonella dispar were grown anaerobically for 64.5
      h at 37 degrees C on hydroxyapatite disks preconditioned with saliva. Conditions
      for the simultaneous in situ hybridization of both Gram-negative and Gram
      positive bacteria were sought by systematic variation of fixation and exposure to
      lysozyme. After fixation and permeabilization biofilms were labeled by FISH with
      16S rRNA-targeted oligonucleotide probes ANA103 (for the detection of A.
      naeslundii), EUK116 (C. albicans), FUS664 (F. nucleatum), MIT447 and MIT588 (S.
      oralis), SOB174 (S. sobrinus), and VEI217 (V. dispar). Probes were used as 6-FAM,
      Cy3 or Cy5 conjugates, resulting in green, orange-red or deep-red fluorescence of
      target cells, respectively. Thus, with two independent triple-hybridizations with
      three probes carrying different fluorescence-tags, all six species could be
      visualized. Results show that the simultaneous investigation by FISH of complex
      biofilms composed of multiple bacterial species with differential Gram-staining
      properties is possible. In combination with the optical sectioning properties of
      CLSM the technique holds great promise for the analysis of spatial alterations in
      biofilm composition in response to environmental challenges.

PMID- 14706750
TI  - A new high-throughput AFLP approach for identification of new genetic
      polymorphism in the genome of the clonal microorganism Mycobacterium
      tuberculosis.
AB  - We have here applied high-throughput amplified fragment length polymorphism
      (htAFLP) analysis to strains belonging to the five classical species of the
      Mycobacterium tuberculosis complex. Using 20 strains, three enzyme combinations
      and eight selective amplification primer pairs, 24 AFLP reactions were performed
      per strain. Overall, this resulted in 480 DNA fingerprints and more than 1200
      htAFLP-amplified PCR fragments were visualised per strain. The cumulative
      dendrogram correctly clustered strains from the various species, albeit within a
      distance of 6.5% for most of them. The single isolate of Mycobacterium canettii
      presented separately at 19% distance. All over, 169 fragments (14%) appeared to
      be polymorphic. Sixty-eight were specific for M. canetti and forty-five for
      Mycobacterium bovis. For the 10 different M. tuberculosis strains included in the
      present analysis, 56 polymorphic markers were identified. Upon sequencing 20 of
      these marker regions and comparisons with the H37Rv genome sequence, 25% appeared
      to share homology to members of the antigenically variable PE/PPE surface protein
      encoding gene family confirming previous findings on the genetic heterogeneity
      within these genes. In addition, homologues for phage genes and insertion element
      encoded genes were detected. Forty-five percent of the sequences derived from
      ORFs with a currently unknown function, which was corroborated by genome sequence
      comparison for the clinical M. tuberculosis CD 1551 isolate. Sequence variation
      in M. tuberculosis was assessed in more detail for a subset of these loci by
      newly designed PCR restriction fragment length polymorphism (RFLP) tests and
      direct sequencing. Fourteen novel PCR RFLP tests were developed and twelve novel
      single nucleotide polymorphisms (SNPs) were identified, all suited for
      epidemiological analysis of M. tuberculosis. The tests allowed for identification
      of the major Mycobacterium species and M. tuberculosis variants and clones.

PMID- 14706751
TI  - Use of a Taqman PCR to determine the response of Mycoplasma haemofelis infection
      to antibiotic treatment.
AB  - A quantitative Taqman polymerase chain reaction (PCR) assay was used to evaluate
      the response of Mycoplasma haemofelis experimentally infected cats to three
      antibiotic treatment regimes. Sixteen cats were intravenously inoculated with M.
      haemofelis from a chronically infected donor. The cats were randomly assigned to
      one of four treatment groups each containing four cats: oral doxycycline at 10
      mg/kg/day for 14 days, oral enrofloxacin at 5 mg/kg/day for 14 days, oral
      enrofloxacin at 10 mg/kg/day for 14 days, and an untreated control group. DNA,
      extracted from blood samples collected on days 0, 7, 14, 21, 25, 28, 32, 35, 42
      and 54 post-inoculation (PI), was subjected to quantitative Taqman PCR. The M.
      haemofelis copy number was significantly lower in the doxycycline group
      (P=0.008), the 5 mg/kg/day enrofloxacin group (P=0.006) and the 10 mg/kg/day
      enrofloxacin group (P=0.005) compared to the untreated control group. No
      significant differences were found between any of the three antibiotic treated
      treatment groups. All three antibiotic treatment regimes evaluated in this study
      were effective at reducing M. haemofelis copy number.

PMID- 14706752
TI  - Fourier transform infrared spectroscopy as a new tool for characterization of
      mollicutes.
AB  - Fourier transform infrared (FT-IR) spectroscopy is a convenient physico-chemical
      technique to investigate various cell materials. Bacteria of class Mollicutes,
      identified by conventional methods, as Mycoplasma, Acholeplasma and Ureaplasma
      genera were characterized using this method. A data set of 74 independent
      experiments corresponding to fourteen reference strains of Mollicutes was
      examined by FT-IR spectroscopy to attempt a spectral characterization based on
      the biomolecular structures. In addition to the separation of Mollicutes within
      the lipidic region into five main clusters corresponding to the three
      phylogenetic groups tested, FT-IR spectroscopy allowed a fine discrimination
      between strains belonging to the same species by using selective spectral
      windows, particularly in the 1200-900 cm(-1) saccharide range. The results
      obtained by FT-IR were in good agreement with both taxonomic and phylogenetic
      classifications of tested strains. Thus, this technique appears to be a useful
      tool and an accurate mean for a rapid characterization of Mollicutes observed in
      humans.

PMID- 14706753
TI  - Use of mixed infections to study cell invasion and intracellular proliferation of
      Salmonella enterica in eukaryotic cell cultures.
AB  - Epithelial cell lines are widely used as an in vitro model to study cell invasion
      by Salmonella. In turn, phagocytic cell lines are used to study Salmonella
      intracellular survival and proliferation. We describe a novel method, derived
      from the classical mixed infection procedure, to quantify invasion and
      proliferation defects in Salmonella enterica serovar Typhimurium. A eukaryotic
      cell culture is infected with two strains (e.g., a mutant and the wild-type).
      After infection, bacterial cells that remain extracellular are eliminated with
      gentamicin. At the end of the trial, intracellular bacteria are recovered and
      plated. Colonies from each strain are then counted for the calculation of a
      competitive index. Strain discrimination can be achieved either with antibiotic
      resistance markers or using plasmids encoding color markers (e.g., fluorescent
      proteins). Because both strains are exposed to the same conditions throughout the
      process, the procedure decreases the variability between independent trials and
      allows a direct measurement of the impairment of the mutant in invasion or
      intracellular proliferation.

PMID- 14706754
TI  - A simple method for differential isolation of freely dispersed and particle
      associated peat microorganisms.
AB  - Differential isolation of physiologically and ecologically diverse microbial
      groups facilitates evaluation of their activities in the environment. Here we
      describe a new method for differential isolation of freely dispersed and particle
      associated peat microorganisms. The method is based on sequential elution of
      peat. Two types of natural peat, "young" sphagnum peat and "old" reed-based peat
      that have significantly different molecular composition as revealed by solid
      state 13C NMR, were used for the method development. Various combinations of
      elution parameters (pH values, surfactant concentration, and sonication) were
      tested. Protein yield, CFU counts, 16S rDNA gene sequence, and T-RFLP analyses
      were used as criteria for evaluating the effectiveness of the elution protocols.
      The optimal method consisted of sequential elutions with (i) pH 6.2, 0.1 M
      potassium phosphate buffer, (ii) the same buffer amended with 0.01% of Tween 80,
      and (iii) treatment (ii) amended with sonication for 2 min. This method allowed
      differential isolation of freely dispersed and particle-associated microorganisms
      with (i) highest yield, (ii) highest diversity within the each microbial
      fraction, and (iii) best discrimination between the freely dispersed and particle
      associated microbial communities. The method was applied for characterization of
      peat microbial communities and revealed different taxonomic composition and
      similar spatial organization of sphagnum and reed-sage peat microorganisms.

PMID- 14706755
TI  - Development of degenerate and specific PCR primers for the detection and
      isolation of known and putative chloroethene reductive dehalogenase genes.
AB  - Degenerate and specific PCR primers were designed for the detection of
      chloroethene reductive dehalogenases (CE-RDase), the key enzymes of chloroethene
      dehalorespiration, based on sequence information of three CE-RDases and three
      chlorophenol (CP) RDases. For the design of the degenerate primers, seven
      conserved amino-acid blocks identified with different bioinformatic tools were
      used. For one block degenerate, primers containing a 5'-consensus clamp region
      specific for CE-RDases and a 3'-end degenerate core region specific for RDases in
      general were designed using the Consensus-Degenerate Hybrid Oligonucleotide
      Primer (CDHOP) design method. Applying the degenerate primers to genomic DNA of
      Sulfurospirillum multivorans strain K, Dehalobacter restrictus strain PER-K23,
      and Desulfitobacterium sp. strain PCE1 led to the isolation of the known CE-RDase
      genes and three new genes encoding putative reductive dehalogenases that cluster
      with CE-RDases and not with CP-RDases. In addition, primers designed to be
      specific for the three known CE-RDase genes, namely pceA of S. multivorans, pceA
      of D. restrictus, and tceA of Dehalococcoides ethenogenes were successfully
      tested on genomic DNA of different chloroethene-dehalorespiring bacteria. Nested
      PCR using degenerate primers followed by a PCR with specific primers allowed a
      sensitive detection of only 10(2) copies per reaction.

PMID- 14706756
TI  - High phosphate (up to 600 mM) induces pseudohyphal development in five wild type
      Candida albicans.
AB  - A method is described for the formation of nearly 100% pseudohyphae populations
      of wild-type Candida albicans A72. The method employs fungal growth at 37 degrees
      C (ca. 5x10(6) cells/ml) in a glucose-proline-N-acetyl-glucosamine medium
      supplemented with up to 600 mM phosphate (KH(2)PO(4)/K(2)HPO(4) 1:1) at pH 6.5.
      Four other strains of C. albicans (MEN, 10261, SG5314 and CAI-4) also formed
      pseudohyphae under these conditions, although the phosphate response profiles
      differed in the concentration required for each strain to form pseudohyphae.

PMID- 14706757
TI  - A facile analytical method for the identification of protease gene profiles from
      Bacillus thuringiensis strains.
AB  - Five pairs of degenerate universal primers have been designed to identify the
      general protease gene profiles from some distinct Bacillus thuringiensis strains.
      Based on the PCR amplification patterns and DNA sequences of the cloned
      fragments, it was noted that the protease gene profiles of the three distinct
      strains of B. thuringiensis subsp. kurstaki HD73, tenebrionis and israelensis
      T14001 are varied. Seven protease genes, neutral protease B (nprB), intracellular
      serine protease A (ispA), extracellular serine protease (vpr), envelope
      associated protease (prtH), neutral protease F (nprF), thermostable alkaline
      serine protease and alkaline serine protease (aprS), with known functions were
      identified from three distinct B. thuringiensis strains. In addition, five DNA
      sequences with unknown functions were also identified by this facile analytical
      method. However, based on the alignment of the derived protein sequences with the
      protein domain database, it suggested that at least one of these unknown genes,
      yunA, might be highly protease-related. Thus, the proposed PCR-mediated
      amplification design could be a facile method for identifying the protease gene
      profiles as well as for detecting novel protease genes of the B. thuringiensis
      strains.

PMID- 14706758
TI  - Photometric assay for measuring the intracellular concentration of branched-chain
      amino acids in bacteria.
AB  - The changes in intracellular pool of branched-chain amino acids (BCAA) regulate
      different physiological processes in bacteria. Up to date, the only available
      photometric test for measuring BCAA concentration was adapted for blood and
      plasma samples in diagnostic purposes. We have modified this method for use on
      bacterial cells, and tested its applicability on several model organisms:
      Lactococcus lactis, Bacillus subtilis and Escherichia coli.

PMID- 14706759
TI  - Simple table for estimating confidence interval of discrepancy frequencies in
      microbiological safety evaluation.
AB  - We provide a simple tool to determine discrepancies confidence interval (CI) in
      microbiology validation studies such as technical accuracy of a qualitative test
      result. This tool enables to determine exact confidence interval (binomial CI)
      from an observed frequency when normal approximation is inadequate, that is, in
      case of rare events. This tool has daily applications in microbiology and we are
      presenting an example of its application to antimicrobial susceptibility systems
      evaluation.

PMID- 14706760
TI  - Soy for the treatment of perimenopausal symptoms--a systematic review.
AB  - OBJECTIVES: Many women have turned to complementary and alternative medicines for
      relief from their perimenopausal symptoms. The prevalence of plant-based medicine
      use among perimenopausal women highlights the need for investigation into these
      interventions. The aim of this study was to evaluate the benefit of soy
      preparations for the treatment of perimenopausal symptoms by performing a
      systematic review of randomised clinical trials (RCTs). METHODS: Literature
      searches were performed using four computerised databases to identify RCTs of soy
      preparations for the treatment of perimenopausal symptoms. Manufacturers of soy
      products were contacted and our own files were also searched. There were no
      restrictions on the language of publication. Trials were considered if they used
      mono-preparations of soy or soy isoflavones, and if the outcome measures related
      to the physical and/or psychological impact of menopause in healthy women and
      scored at least three on the Jadad scale. RESULTS: Thirteen RCTs were identified
      that investigated the use of soy preparations for perimenopausal symptoms. Ten of
      these trials fitted our inclusion criteria. The results of these studies are not
      conclusive. Four of these randomised controlled trials were positive, suggesting
      soy preparations are beneficial for perimenopausal symptoms. Six were negative;
      with one of the six showing a positive trend. CONCLUSIONS: There is some evidence
      for the efficacy of soy preparations for perimenopausal symptoms. However, the
      heterogeneity of the studies performed to date means it is difficult to make a
      definitive statement. Adverse event data from the trials suggest that there are
      no serious safety concerns with soy products in short-term use.

PMID- 14706761
TI  - Soy isoflavones and melatonin for the relief of climacteric symptoms: a
      multicenter, double-blind, randomized study.
AB  - OBJECTIVE: To evaluate the effect of soy isoflavones and melatonin in relieving
      menopausal symptoms. METHODS: Double-blind, multicenter, randomized trial
      performed according to a 2 x 2 factorial design. Treatment groups: (1) soy
      isoflavones+melatonin; (2) soy isoflavones alone; (3) melatonin alone; (4)
      placebo. 80 mg of soy isoflavones, 3 mg of pure melatonin or placebo were
      supplemented to participants for 3 months. Severity of menopausal symptoms was
      recorded at baseline and after 3 months using the Greene Climacteric Scale.
      RESULTS: 388 consecutive women were screened: not eligible 98, refused informed
      consent 28. Randomized 262 and analyzed 232; twelve women withdrew because of
      adverse events. Median percent differences between basal and final scores were
      39% in the isoflavones + melatonin group, 38% in the isoflavones alone group, 26%
      in the melatonin alone group and 38% in the placebo group. Placebo response was
      much higher than planned, making it meaningless to perform any statistical test.
      With regard to somatic and vasomotor symptoms, outcome was similar among the four
      groups, whereas improvement of psychological symptoms was higher in the
      isoflavones+melatonin group than in the other three. CONCLUSIONS: Present data do
      not show any advantage of isoflavones or melatonin over placebo for the relief of
      menopausal symptoms. However, the effect in psychological symptoms in the
      isoflavones + melatonin group should be further investigated.

PMID- 14706762
TI  - Design and baseline characteristics of a trial on health effects of soy protein
      with isoflavones in postmenopausal women.
AB  - This study is a double-blind, randomized, placebo-controlled trial to assess the
      effects of high amounts of phytoestrogens on bone mineral density, cardiovascular
      diseases, cognitive function, performance in activities of daily life and well
      being. Participants were healthy postmenopausal women, aged 60-75 years. Between
      March and September 2000, 202 women were recruited, and, after completion of the
      baseline measurements, randomized to either soy protein, containing 99 mg
      naturally occurring isoflavones or placebo (milk protein) daily for 1 year.
      Analysis of the endpoints will be based on the difference between baseline
      measurements and measurements at the end of the intervention period with group
      allocation as independent variable.

PMID- 14706763
TI  - Knowledge and use of hormone replacement therapy among Polish women: estimates
      from a nationally representative study--HORTPOL 2002.
AB  - OBJECTIVES: To evaluate the knowledge about hormone replacement therapy (HRT) and
      the prevalence of its current use in Polish female population. METHODS: Cross
      sectional survey on a representative sample of 1544 women between 18 and 87 years
      of age. RESULTS: Almost half of the Polish women have heard of HRT. Depending on
      the education level, 26-38% of women knew that HRT alleviates the physical and
      psychological symptoms of menopause and 18-32% knew that HRT reduces the risk of
      developing osteoporosis. Forty-three percent of all the women with a higher level
      of education were aware that HRT increases the risk of breast and uterine cancer.
      The prevalence of current HRT use among women aged 45-64 was 12%. Women who had
      only basic education were less likely to use HRT than those with a medium and
      higher education level. Lack of information about HRT was the main cause of not
      using it. Forty-four percent of the perimenopausal women (age range 45-54 years)
      have never heard of HRT and 36% were never told by their healthcare providers
      that they could use it. Nineteen percent of perimenopausal women were not using
      HRT because they were afraid of the HRT related risks. Sixty-four percent of
      women who were using HRT were prescribed oral HRT preparations. CONCLUSIONS: A
      fairly small proportion of Polish women currently uses HRT, largely because most
      remain poorly informed about the therapy.

PMID- 14706764
TI  - Associated response in bone and lipids during hormone replacement therapy.
AB  - OBJECTIVE: In postmenopausal women, we investigated if the response in bone
      mineral density (BMD) was associated with the response in the atherogenic lipid
      profile during hormone replacement therapy. METHODS: We performed an exploratory,
      post-hoc analysis of data from a prospective double-blind placebo-controlled
      trial. Healthy postmenopausal women were randomised into five groups, each
      receiving different combinations of 17 beta-estradiol and gestodene or placebo. A
      total of 133 women completed the study. The study period was 3 years. The
      response in bone mass was expressed as the percentage change in BMD from baseline
      calculated by linear regression from semi-annual measurements. The change in
      lipid profile was evaluated as the average of three mid-cycle and end-cycle
      values in percentage from baseline in order to account for cyclic changes during
      sequential hormone therapy. RESULTS: A significant correlation between the
      increase in BMD of the spine and hip and forearm with the decrease in serum low
      density lipoprotein (LDL) and cholesterol was found. Additionally, the decrease
      in atherogenic lipids correlated significantly with the response in biochemical
      bone markers for resorption and formation. CONCLUSION: In conclusion, our study
      shows that it is the same women who have a favourable response in BMD as in the
      lipid-profile during hormone replacement therapy (HRT). The association is most
      likely driven by a common response in FSH to exogenous estradiol therapy. This
      indicates that common denominators for the response to HRT exist. Further studies
      are needed to explore and identify such predictors.

PMID- 14706765
TI  - Low-dose (0.3 mg) synthetic conjugated estrogens A is effective for managing
      atrophic vaginitis.
AB  - OBJECTIVE: Estrogen or combined hormone (estrogen-progestin) therapy is highly
      efficacious for managing the signs and symptoms of urogenital atrophy. A low,
      effective estrogen dose may enhance patient acceptance and reduce side effects.
      METHODS: In this randomized, double-blind, multicenter clinical trial, 71 healthy
      postmenopausal women with vaginal atrophy (Vaginal Maturation Index < or =55)
      received either low-dose synthetic conjugated estrogens, A tablets (Cenestin)
      (SCE-A), 0.3 mg once daily, or placebo for 16 weeks. RESULTS: Treatment with SCE
      A for 16 weeks resulted in a highly significant (P<0.0001) mean increase of 17.7
      in the Vaginal Maturation Index compared to a mean increase of 4.1 with placebo
      treatment. A significant estrogenic improvement was detected as early as 4 weeks
      (mean increase 14.6). Superficial cells were significantly increased from 2.1% at
      baseline to 15.9% at week 16 with SCE-A, and parabasal cells were significantly
      reduced from 23.0% at baseline to 1.6% at week 16 (P<0.01 between treatments for
      both). Vaginal pH was significantly decreased from 6.2 at week -2 to 5.2 at week
      16 with SCE-A compared to placebo (P<0.0001). There were no significant
      differences between treatment groups in the incidence of treatment-emergent side
      effects or other measures of safety, except for urinary tract infection, which
      occurred more frequently in the placebo group. CONCLUSIONS: These results confirm
      the relatively rapid estrogenic effect and safety of a low-dose (0.3 mg/day) of
      slow-release SCE-A (Cenestin) in the treatment of vaginal atrophy in
      postmenopausal women.

PMID- 14706766
TI  - Age-related change in the strength of correlation of lumbar spine bone mineral
      density with other regions.
AB  - OBJECTIVES: To investigate whether the strength of correlation of lumbar spine
      bone mineral density (BMD) with other regions differs with age. METHODS: Subjects
      were 336 premenopausal women aged 20-49 years and 218 postmenopausal women aged
      50-69 years with right-side dominance. Age, height, weight, and years since
      menopause (YSM) were recorded. Subjects were classified into five subgroups at 10
      year increments. BMD of the arms, lumbar spine (L2-4), pelvis, legs, and total
      body were measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Regional
      and total body BMD did not differ among women aged in their 20s, 30s, and 40s.
      However, in women aged over 50, regional and total body BMD gradually decreased
      with age. The strength of correlation of lumbar spine BMD with the left arm,
      right arm, left leg, right leg, and total body BMD gradually increased with
      advancing age (r=0.422-0.715, 0.376-0.714, 0.476-0.721, 0.491-0.734, and 0.642
      0.800, respectively). However, the strength of correlation of lumbar spine BMD
      with pelvis BMD remained unchanged (r=0.512-0.622). CONCLUSIONS: Correlation of
      lumbar spine BMD with extremities BMD gradually strengthens with advancing age,
      while higher correlation of lumbar spine BMD with pelvis BMD remains unchanged.
      When lumbar spine BMD is predicted using values at sites such as forearm BMD, we
      should consider the patient's age.

PMID- 14706767
TI  - Hysterectomy and oophorectomy are unrelated to bone loss in older women.
AB  - OBJECTIVE: The relation of hysterectomy and oophorectomy to change in bone
      mineral density (BMD) was examined in older women using and not using estrogen
      replacement therapy (ERT). METHODS: Women aged 60-80 years from the Rancho
      Bernardo Study attended clinic visits in 1988-1991 and 1992-1995 when
      hysterectomy and oophorectomy were ascertained, ERT use was validated and spine
      and hip BMD was assessed at both visits with DEXA. Women were either current ERT
      users or nonusers at both visits. RESULTS: Among these 447 women, average age was
      71 (S.D.=9.0); average years postmenopause was 24.7 (S.D.=10.9). Overall, 122 had
      a hysterectomy with ovarian conservation and 91 had a hysterectomy with bilateral
      oophorectomy; 41% reported current ERT use for an average duration of 19.1 years
      (S.D.=10.8). Hysterectomized women were 2.3 times more likely to report ERT use
      than intact women (P<0.001). Comparisons adjusted for age, obesity, and age at
      menopause but not for ERT use showed hysterectomized women had less bone loss per
      year at the hip than intact women (P<0.05). However, this difference was
      explained by ERT; after adjustment for ERT, mean hip bone loss per year was 
      0.57% for intact women, -0.42% for hysterectomized women with ovarian
      conservation and -0.32% for bilaterally oophorectomized women (P's>0.10). There
      were no differences by hysterectomy or oophorectomy in bone loss at the spine or
      femoral neck. For all sites, women using ERT had higher BMD at both visits than
      nonusers (P's<0.001). Stratification by ERT showed that within users and
      nonusers, there were no differences in BMD or bone loss at any site by
      hysterectomy or oophorectomy. CONCLUSIONS: There are no long term effects of
      hysterectomy and bilateral oophorectomy on bone loss. Women who use ERT have
      better BMD than nonusers.

PMID- 14706768
TI  - The effect of exercise on physical fitness and quality of life in postmenopausal
      women.
AB  - OBJECTIVES: This study was designed to determine the effect of exercise on the
      physical fitness level and quality of life in postmenopausal women. 81 volunteer
      postmenopausal women who entered the menopause naturally and have been taking
      hormone replacement treatment (HRT) were divided randomly into two groups:
      exercise (n=41) and control (n=40). METHODS: Physical fitness tests and the
      Nottingham Health Profile (NHP) were used to assess physical fitness and quality
      of life in both groups, both before and after 6 weeks. The study group
      participated in an exercise programme, which was composed of sub-maximal aerobic
      exercises for a 6-week period 3 times a week. The statistical analyses were done
      by paired samples t-test and independent samples t-test. RESULTS: At the end of 6
      weeks exercise period, when the two groups were compared after the exercise
      period, we found statistically significant differences in strength, endurance,
      flexibility and balance parameters in the exercise group (P<0.05). There was also
      a statistically significant change in the exercise group for the NHP indicating
      an improvement in the quality of life (P<0.05). CONCLUSIONS: In this study, it
      was concluded that the fitness level and quality of life on postmenopausal women
      could be improved by a regular and controlled exercise programme of 6 weeks.

PMID- 14706770
TI  - A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of
      Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and
      affects the CNS. Dystrophin is absent in muscle and CNS of both DMD patients and
      mdx mouse, a model of DMD. While the involvement of vascular compartment in DMD
      was poorly investigated, some studies suggested a role for mast cells (MC).
      Tryptase, contained in the MC granules, stimulates angiogenesis in vitro and in
      vivo. We demonstrated for the first time a correlation between the extent of
      angiogenesis and the number of tryptase-positive neurons and microvessels and
      suggest that the tryptase contained in the neurons and in the endothelial cells
      of the mdx mouse brain may be involved in the regulation of angiogenesis taking
      place in mdx mouse.

PMID- 14706771
TI  - Urocortin expression in the Edinger-Westphal nucleus is down-regulated in
      transgenic mice over-expressing neuronal corticotropin-releasing factor.
AB  - In recent years a large body of evidence has emerged linking chronic stress with
      increased vulnerability for depression and anxiety disorders. As corticotropin
      releasing factor (CRF) is hypersecreted under these psychological conditions, we
      used our CRF-overexpressing (CRF-OE) mouse line to study underlying brain
      mechanisms possibly causing these disorders. Urocortin (Ucn), a recently
      discovered member of the CRF peptide family may play a role in the
      pathophysiology of stress-induced disorders. Stressors recruit Ucn-immunoreactive
      neurons in the Edinger-Westphal nucleus (E-WN), which is the major site of Ucn
      expression. Furthermore, E-WN Ucn mRNA levels are upregulated in CRF-deficient
      mice. Based on these findings, we hypothesized the down-regulation of E-WN Ucn in
      CRF-OE mice and consequently, altered responsiveness to stressful stimuli. Our
      results support this hypothesis as we found weaker immunohistochemical labeling
      with anti-Ucn and a six times weaker Ucn mRNA signal in E-WN in CRF-OE mice.
      Moreover, E-WN Ucn-expressing neurons mounted a response to acute challenge in
      CRF-OE mice too. From these results it is concluded that the CRF and E-WN Ucn
      neuronal systems work in concert in response to acute challenges, but are
      inversely regulated in their activities during chronic hyperactivity of the
      hypothalamo-pituitary-adrenal axis.

PMID- 14706772
TI  - A role for extracellular metallothioneins in CNS injury and repair.
AB  - For many years, research focus on metallothioneins, small zinc binding proteins
      found predominantly within astrocytes in the brain, has centred on their ability
      to indirectly protect neurons from oxygen free radicals and heavy metal-induced
      neurotoxicity. However, in recent years it has been demonstrated that these
      proteins have previously unsuspected roles within the cellular response to brain
      injury. The aim of this commentary is to provide an overview of the exciting
      recent experimental evidence from several laboratories including our own
      suggesting a possible extracellular role for these proteins, and to present a
      hypothetical model explaining the newly identified function of extracellular
      metallothioneins in CNS injury and repair.

PMID- 14706773
TI  - The hypothalamic-pituitary-adrenal and glucose responses to daily repeated
      immobilisation stress in rats: individual differences.
AB  - It is accepted that there are important individual differences in the
      vulnerability to stress-induced pathologies, most of them associated to the
      hypothalamic-pituitary and sympatho-medullo-adrenal axes, the two prototypical
      stress-responsive systems. However, there are few studies specifically aimed at
      characterising individual differences in the physiological response to daily
      repeated stress in rats. In the present work, male rats were submitted to
      repeated immobilisation (IMO) stress (1 h daily for 13 days) and several samples
      were taken at specific days and time points. Animals only subjected to blood
      sampling procedure served as controls. Daily adrenocorticotropic-hormone (ACTH),
      corticosterone and glucose responses to immobilisation (that included the post
      immobilisation period) progressively declined over the days. In addition,
      repeated immobilisation resulted in decreased relative thymus weight, increased
      relative adrenal weight, elevated corticotropin-releasing factor (CRF) mRNA
      levels in the hypothalamic paraventricular nucleus (PVN), and down-regulation of
      glucocorticoid receptor gene transcription in hippocampus CA1. However, only CRF
      mRNA levels in the paraventricular nucleus correlated with the ACTH (on day 1)
      and corticosterone responses (from day 4-13) to immobilisation. When the animals
      were classified in three groups on the basis of their plasma ACTH levels
      immediately after the first immobilisation, individual differences in the ACTH
      response progressively disappeared on successive exposures to the stressor,
      whereas those in corticosterone and glucose were more sustained. The present
      results suggest that there are individual differences in the physiological
      response to stress that tend to be reduced rather than accentuated by repeated
      exposure to the stressor. Nevertheless, this buffering effect of repeated stress
      was dependent on the particular variable studied.

PMID- 14706774
TI  - Individual responses to novelty predict qualitative differences in d-amphetamine
      induced open field but not reward-related behaviors in rats.
AB  - Differences in the locomotor response of rats to a novel environment (high
      responders [HR] versus low responders [LR]) have been associated with differences
      in vulnerability to psychostimulants. In the present study we profiled
      extensively the behavioral repertoire of HR and LR rats (differentiated on the
      basis of vertical activity) during exposure to a novel environment and in
      response to d-amphetamine (d-amp; 1.5 mg/kg, i.p.). Moreover, we ascertained
      whether HR and LR rats differ in the rewarding effects of medial forebrain bundle
      electrical self-stimulation and in the ability of d-amp to increase the
      reinforcing efficacy of self-stimulation. Apart from rearing, HR animals
      displayed increased moving, sniffing, but decreased standing and yawning compared
      with LR. Factor analysis revealed a more complex behavioral structure consisting
      of locomotion, exploration, vertical activity and self-directed behavior for HR
      compared with LR rats. Qualitative, but not quantitative differences, between the
      two groups of rats in their behavioral responses to d-amp were found. In
      particular, a more complex profile mainly characterized by self-directed
      behavior, locomotion and vertical activity was manifested for HR as compared with
      LR rats. Baseline brain stimulation reward thresholds did not differ between the
      two groups of rats. Additionally, brain stimulation reward thresholds for the two
      groups were not differentially affected by d-amp. The above results suggest that
      HR and LR can be further differentiated upon exposure to a novel environment and
      in response to d-amp. This differentiation is primarily based on qualitative
      cohorts of their behavioral structure, but not on deviations in the reward
      processes as assessed by intracranial self-stimulation.

PMID- 14706775
TI  - N-methyl-D-aspartate receptors in the amygdala are necessary for the acquisition
      and expression of conditioned defeat.
AB  - Here, we describe a biologically relevant model called conditioned defeat that is
      used to examine behavioral responses to social defeat in Syrian hamsters. In this
      model experimental animals that are normally aggressive experience social defeat
      and consequently display high levels of submissive/defensive behavior even in
      response to non-threatening conspecifics. N-methyl-D-aspartate (NMDA) receptors
      within the amygdala play an important role in conditioned fear; therefore, the
      purpose of this study was to examine whether NMDA receptors within the amygdala
      are necessary for the acquisition and expression of conditioned defeat.
      Specifically, the present study examined whether bilateral infusions of the NMDA
      receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5; 0.625, 1.25, 2.5,
      5.0, 10.0 microg) into the amygdala would block the acquisition of conditioned
      defeat. Subsequently, we examined whether bilateral infusions of AP5 (0.625,
      1.25, 2.5, 5.0 microg) into the amygdala prior to testing would block the
      expression of conditioned defeat. Infusions of AP5 into the amygdala immediately
      before the initial social defeat significantly reduced submissive/defensive
      behavior when hamsters were tested the following day with a non-aggressive
      intruder. Similarly, infusions of AP5 into the amygdala immediately before
      exposure to a non-aggressive intruder significantly attenuated the display of
      submissive/defensive behavior. These data demonstrate that NMDA receptors are
      necessary for both the acquisition and expression of conditioned defeat. We
      believe that conditioned defeat is a unique and valuable animal model with which
      to investigate the neurobiology of fear-related changes in social behavior.

PMID- 14706776
TI  - Neuronal activity in the nucleus accumbens is necessary for performance-related
      increases in cortical acetylcholine release.
AB  - In vivo microdialysis was used to determine the necessity of neuronal activity in
      the nucleus accumbens (NAC) for task-induced increases in cortical acetylcholine
      (ACh) efflux. Rats were trained in a behavioral task in which they were required
      to perform a defined number of licks of a citric acid solution in order to gain
      access to a palatable, cheese-flavored food. Upon reaching a consistent level of
      performance, rats were implanted with microdialysis cannula in the medial
      prefrontal cortex (mPFC) and either the ipsilateral shell of the NAC or in the
      dorsal striatum (STR; control site). Dialysis samples from the mPFC were analyzed
      for ACh concentrations and samples from the NAC were analyzed for dopamine (DA)
      concentrations. Performance in the task was associated with increases in both ACh
      efflux in the cortex (150-200%) and DA efflux in the NAC (50-75%). These
      increases were blocked by administration of tetrodotoxin (TTX; 1.0 microM) via
      reverse dialysis into the NAC. Administration of TTX into the dorsal STR control
      site was ineffective in blocking performance-associated increases in cortical
      ACh. The D2 antagonist sulpiride (10 or 100 microM) administered into the NAC via
      reverse dialysis was ineffective in blocking increases in cortical ACh efflux.
      The present data reveal that neuronal activity in the NAC is necessary for
      behaviorally induced increases in cortical ACh efflux and that this activation
      does not require increases in D2 receptor activity.

PMID- 14706777
TI  - Differential effects of testosterone on protein synthesis activity in male and
      female quail brain.
AB  - In Japanese quail, testosterone (T) increases the Nissl staining density in the
      medial preoptic nucleus (POM) in relation to the differential activation by T of
      copulatory behavior. The effect of T on protein synthesis was quantified here in
      97 discrete brain regions by the in vivo autoradiographic (14)C-leucine (Leu)
      incorporation method in adult gonadectomized male and female quail that had been
      treated for 4 weeks with T or left without hormone. T activated male sexual
      behaviors in males but not females. Overall Leu incorporation was increased by T
      in five brain regions, many of which contain sex steroid receptors such as the
      POM, archistriatum and lateral hypothalamus. T decreased Leu incorporation in the
      medial septum. Leu incorporation was higher in males than females in two nuclei
      but higher in females in three nuclei including the hypothalamic ventromedial
      nucleus. Significant interactions between effects of T and sex were seen in 13
      nuclei: in most nuclei (n=12), T increased Leu incorporation in males but
      decreased it in females. The POM boundaries were defined by a denser Leu
      incorporation than the surrounding area and incorporation was increased by T more
      in males (25%) than in females (6%). These results confirm that protein synthesis
      in brain areas relevant to the control of sexual behavior can be affected by the
      sex of the subjects or their endocrine condition and that T can have differential
      effects in the two sexes. These anabolic changes should reflect the sexually
      differentiated neurochemical mechanisms mediating behavioral activation.

PMID- 14706778
TI  - Motor balance and coordination training enhances functional outcome in rat with
      transient middle cerebral artery occlusion.
AB  - The goal of this study was to determine if relatively complex motor training on
      Rota-rod involving balance and coordination plays an essential role in improving
      motor function in ischemic rats, as compared with simple locomotor exercise on
      treadmill. Adult male Sprague-Dawley rats with (n=40) or without (n=40) ischemia
      were trained under each of three conditions: (1) motor balance and coordination
      training on Rota-rod; (2) simple exercise on treadmill; and (3) non-trained
      controls. Motor function was evaluated by a series of tests (foot fault placing,
      parallel bar crossing, rope and ladder climbing) before and at 14 or 28 days
      after training procedures in both ischemic and normal animals. Infarct volume in
      ischemic animals was determined with Nissl staining. Compared with both treadmill
      exercised and non-trained animals, Rota-rod-trained animals with or without
      ischemia significantly (P<0.01) improved motor performance of all tasks except
      for foot fault placing after 14 days of training, with normal rats having better
      performance. Animals trained for up to 28 days on the treadmill did not show
      significantly improved function. With regard to foot fault placing task,
      performance on foot placing was improved in ischemic rats across the three
      measurements at 0, 14 and 28 days regardless of training condition, while the
      normal group reached their best performance at the beginning of measurement. No
      significant differences in infarct volume were found in rats trained either with
      Rota-rod (47+/-4%; mean+/-S.E.), treadmill (45+/-5%) or non-exercised control
      (45+/-3%). In addition, no obvious difference could be detected in the location
      of the damage which included the dorso-lateral portion of the neostriatum and the
      frontoparietal cortex, the main regions supplied by the middle cerebral artery.
      The data suggest that complex motor training rather than simple exercise
      effectively improves functional outcome.

PMID- 14706779
TI  - The ventral hippocampal regulation of prepulse inhibition and its disruption by
      apomorphine in rats are not mediated via the fornix.
AB  - Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is
      impaired in schizophrenia. We have reported that PPI is regulated by the ventral
      hippocampus (VH) and that the PPI disruptive effects of the dopamine agonist
      apomorphine are enhanced 4 weeks after excitotoxic lesions of the VH. The
      mechanisms responsible for the VH influence on PPI are not understood, but have
      been ascribed to interactions between the VH and nucleus accumbens. In the
      present study, we examined whether the VH influence on PPI and its dopaminergic
      regulation is dependent on the integrity of the VH-accumbens projection via the
      fornix. First, the PPI-disruptive effects of intra-VH NMDA infusion were assessed
      after sham or electrolytic transection of the fornix. Second, the PPI-disruptive
      effects of apomorphine were assessed 1 month after excitotoxic or electrolytic
      lesions of the VH, or after fornix transection. Intra-VH N-methyl-D-aspartate
      infusion significantly disrupted PPI; this effect was unaffected by fornix
      lesions. The PPI-disruptive effects of apomorphine were significantly enhanced by
      excitotoxic or electrolytic lesions of the VH, but not by fornix transection. The
      influence of the VH on PPI and its dopaminergic regulation does not appear to be
      mediated via the fornix. The enhanced sensitivity to the PPI-disruptive effects
      of apomorphine after VH lesions is not dependent on excitotoxin-induced changes
      in the VH or its downstream projections.

PMID- 14706780
TI  - Lysophosphatidic acid stimulates calcium transients in enteric glia.
AB  - The enteric nervous system plays an integral role in the gastrointestinal tract.
      Within this intricate network, enteric glia are crucial in the maintenance of
      normal bowel function, yet their signaling mechanisms are poorly understood.
      Enteric glia, and not enteric neurons, selectively responded to lysophosphatidic
      acid (LPA), a product of phosphatidylcholine metabolism, with dose-dependent
      calcium (Ca(2+)) signaling over a range from 100 pM to 10 microM. The elicited
      calcium transients involved both the mobilization of intracellular Ca(2+) stores
      and the influx of extracellular Ca(2+) as LPA signals were obliterated following
      the depletion of intracellular Ca(2+) and attenuated by the removal of Ca(2+)
      from the perfusion buffer. Pretreatment with pertussis toxin (100 ng/ml) reduced
      the magnitude of LPA Ca(2+) transients (95+/-20 nM vs 168+/-17 nM for controls).
      Repetitive exposure yielded diminished responsiveness, with a 25% reduction in
      [Ca(2+)](i) between first and second exposures. Inhibition of the inositol 1,4,5
      trisphosphate (IP(3)) receptor with 200 microM 2-aminoethoxydiphenylborate (2APB)
      abolished LPA signals. RT-PCR analysis demonstrated the presence of two LPA
      coupled endothelial differentiation gene (EDG) receptor mRNAs (EDG-2 and EDG-7)
      in myenteric plexus primary cultures. EDG-2 expression in glial cells of the ENS
      was confirmed immunocytochemically.

PMID- 14706781
TI  - Brain-derived neurotrophic factor induces rapid morphological changes in
      dendritic spines of olfactory bulb granule cells in cultured slices through the
      modulation of glutamatergic signaling.
AB  - While the acute physiological effects of brain-derived neurotrophic factor (BDNF)
      have been well demonstrated, little is known regarding possible morphological
      effects that occur within a short period of time. The acute effects of BDNF on
      dendritic spine morphology were examined in granule cells in cultured main
      olfactory bulb slices. Organotypic slices prepared from 7-day-old rats were
      cultured for 1 day, and BDNF was applied at varying time points prior to
      fixation. Granule cell dendrites were labeled with a membrane dye and observed
      with a confocal laser scanning microscope. The addition of BDNF into the culture
      medium 6 h before fixation decreased the mean diameter of the dendritic processes
      (filopodia/spines), but the length and density of the processes were not
      affected. Both filopodia/spines in the external plexiform layer and those in the
      granule cell layer exhibited similar changes. Considering the slow penetration
      into the slices, BDNF was then applied to the top of each slice. When applied 1 h
      before fixation, 5 ng and 0.5 ng of BDNF induced the same changes in the external
      plexiform layer and the granule cell layer, respectively. The changes became
      detectable as early as 30 min when 50 ng of BDNF was applied. The pretreatment
      with tetanus toxin or an N-methyl-D-aspartate receptor antagonist abolished the
      acute effects of BDNF on spine morphology. These results indicate that BDNF can
      alter spine morphology within a shorter period of time than previously observed
      and that the effects are mediated by enhanced glutamatergic signaling.

PMID- 14706782
TI  - Effects of early environment on field CA2 pyramidal neurons in the guinea-pig.
AB  - Previous work showed that isolation rearing produces remarkable changes in the
      dendritic pattern and soma of the principal neurons in the dentate gyrus and
      hippocampal fields CA3 and CA1 of the guinea-pig. The aim of the present study
      was to obtain information about the effects of early postnatal isolation on
      neuron morphology in field CA2, the "resistant sector" of the hippocampal
      formation. Male and female guinea-pigs were assigned at 6-7 days of age to either
      a control (social) or an isolated environment where they remained for 80-90 days.
      The apical and basal dendritic trees and the soma of CA2 pyramidal neurons were
      analyzed and quantified in Golgi-stained brains. The results showed that in both
      males and females early isolation caused no effects on the length and dendritic
      branching density of the apical tree of field CA2 pyramidal neurons. In males but
      not in females isolation caused a spine density reduction in the inner apical
      tree. Isolation notably influenced the morphology of the basal tree, but in males
      only. Isolated males exhibited a significant reduction in the length of the basal
      tree and number of dendritic branches accompanied by a reduction in spine
      density. The comparison of animals reared in the same environment showed that in
      the control environment males had more apical and basal dendritic branches and a
      larger neuron soma than females. In the isolated environment the sex differences
      in the apical tree disappeared and those in the basal tree changed direction.The
      results demonstrate structural changes in field CA2 pyramidal neurons following
      neonatal isolation, with a specific reactivity to environment of the basal tree
      of males. The dendritic atrophy in field CA2 of isolated males is in line with
      previous evidence that males react to isolation mainly with dendritic atrophy,
      though field CA2 neurons appear to be less damaged than those of the other
      hippocampal fields. This is in line with the resistance of this field to
      neurodegeneration. The absence of structural changes in field CA2 of isolated
      females confirms, once again, that males are more liable to be endangered by
      early isolation than females.

PMID- 14706783
TI  - Homogenous glycine receptor expression in cortical plate neurons and Cajal
      Retzius cells of neonatal rat cerebral cortex.
AB  - Glycinergic membrane responses have been described in cortical plate neurons
      (CPn) and Cajal-Retzius cells (CRc) during early neocortical development. In
      order to elucidate the functional properties and molecular identity of glycine
      receptors in these two neuronal cell types, we performed whole-cell patch-clamp
      recordings and subsequent single-cell multiplex reverse transcriptase-polymerase
      chain reaction (RT-PCR) analyses on visually identified neurons in tangential and
      coronal slices as well as in situ hybridizations of coronal slices from neonatal
      rat cerebral cortex (postnatal days 0-4). In both CPn and CRc the glycinergic
      agonists glycine, beta-alanine and taurine induced inward currents with larger
      current densities in CRc. The functional properties of these currents were
      similar between CPn and CRc. In both cell types the glycine receptor showed a
      higher affinity for glycine than for the glycinergic agonists beta-alanine and
      taurine. The glycinergic responses of both cells were blocked by the glycinergic
      antagonist strychnine and were unaffected by the GABAergic antagonist bicuculline
      (100 microM), the N-methyl-D-aspartic acid receptor antagonist (+/-)-2-amino-5
      phosphonopentatonic acid (60 microM) and by picrotoxin (30 microM), an antagonist
      of alpha homomeric glycine receptors. Single-cell multiplex RT-PCR revealed the
      expression of glycine receptor alpha(2) and beta subunits in CPn and CRc, while
      no alpha(1) and alpha(3) subunits were observed. In situ hybridization
      histochemistry showed the expression of mRNAs for alpha(2) and beta subunits
      within the cortical plate and in large neurons of the marginal zone, while there
      were no signals for alpha(1) and alpha(3) subunits. In summary, these results
      suggest that CPn and CRc express glycine receptors with similar functional and
      pharmacological properties. The correlation of pharmacological properties and
      mRNA expression suggests that the glycine receptors in both cell types may
      consist of alpha(2)/beta heteromeric receptors.

PMID- 14706784
TI  - Region specific changes in forebrain 5-hydroxytryptamine1A and 5
      hydroxytryptamine2A receptors in isolation-reared rats: an in vitro
      autoradiography study.
AB  - The neurochemical correlates of the behavioural consequences of isolation rearing
      of rats are complex and involve many neurotransmitters, including the
      serotonergic system. Impaired functioning of the ascending serotonergic system
      has been implicated in many neuropsychiatric syndromes, including attention
      deficit hyperactivity disorder and schizophrenia. In the present investigation
      serotonergic function was assessed using in vitro receptor autoradiography. The 5
      hydroxytryptamine(2A) (5-HT(2A)) receptor antagonist [(3)H]ketanserin and the 5
      HT(1A) receptor antagonist, [(3)H]WAY100, 635 were used to compare 5-HT receptor
      subtype densities in the forebrains of socially and isolation-reared rats.
      Regions of highest receptor density were observed in the frontal cortex for 5
      HT(2A) receptors and in the frontal cortex, dorsal hippocampus and lateral septum
      for 5-HT(1A) receptors. In isolation-reared rats, 5-HT(2A) receptor binding site
      densities were significantly increased by between 36 and 67% in the prelimbic,
      motor and cingulate cortices compared with socially reared controls. By contrast,
      5-HT(1A) receptor binding site densities were significantly reduced by 22% in the
      prelimbic cortex, and significantly increased by between 10 and 50% in the motor
      cortex, somatosensory cortex, dentate gyrus and CA fields of the hippocampus.
      These data demonstrate that isolation-rearing produces significant effects on
      forebrain 5-HT(1A) and 5-HT(2A) receptor densities in the adult rat. It is
      hypothesised that altered serotonergic function, particularly in the hippocampus
      and prefrontal cortex, may underlie some of the behavioural abnormalities
      associated with isolation-rearing.

PMID- 14706785
TI  - Mu opioid control of the N-methyl-D-aspartate-evoked release of [3H]
      acetylcholine in the limbic territory of the rat striatum in vitro: diurnal
      variations and implication of a dopamine link.
AB  - Using an in vitro microsuperfusion procedure, the release of newly synthesized
      [(3)H]-acetylcholine (ACh), evoked by N-methyl-D-aspartate (NMDA) receptor
      stimulation, was investigated in striosome-enriched areas and matrix of the rat
      striatum. The role of micro-opioid receptors, activated by endogenously released
      enkephalin, on the NMDA-evoked release of ACh was studied using the selective
      micro-opioid receptor antagonist, beta-funaltrexamine. Experiments were performed
      2 (morning) or 8 (afternoon) h after light onset, in either the presence or
      absence (alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis) of
      dopaminergic transmission. As expected, based on the presence of micro-opioid
      receptors in striosomes, beta-funaltrexamine (0.1 nM, 10 nM and 1 microM)
      enhanced the NMDA (1 mM+10 microM D-serine)-evoked release of ACh in striosome
      enriched areas but not in the matrix. Interestingly, these responses were
      significantly more pronounced in afternoon than in morning experiments. In the
      presence of alpha-methyl-p-tyrosine, the NMDA-evoked release of ACh was increased
      with similar amplitude in morning and afternoon experiments. However, in this
      condition (without dopamine transmission), the facilitatory effects of beta
      funaltrexamine on the NMDA-evoked release of ACh were suppressed totally in the
      morning and only partially in the afternoon. The selective micro-opiate agonist,
      [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (1 microM, coapplied with NMDA), was
      without effect on the NMDA-evoked release of ACh but abolished both dopamine
      dependent (morning) and dopamine-independent (afternoon) responses of beta
      funaltrexamine (10 nM and 1 microM).Therefore, in the limbic territory of the
      striatum enriched in striosomes, the micro-opioid-inhibitory regulation of ACh
      release follows diurnal rhythms. While dopamine is required for this regulation
      in the morning and the afternoon, an additional dopamine-independent process is
      present only in the afternoon.

PMID- 14706786
TI  - Detection and mapping of quantitative trait loci that determine responsiveness of
      mice to nitrous oxide antinociception.
AB  - Exposure to 70% N(2)O evokes a robust antinociceptive effect in C57BL/6 (B6) but
      not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative
      trait loci (QTL) in the mouse genome that might determine responsiveness to
      N(2)O. Offspring from the F(2) generation bred from B6 and D2 progenitors
      exhibited a broad range of responsiveness to N(2)O antinociception as determined
      by the acetic acid-induced abdominal constriction test. QTL analysis was then
      used to dissect this continuous trait distribution into component loci, and to
      map them to broad chromosomal regions. To this end, 24 spleens were collected
      from each of the following four groups: male and female F(2) mice responding to
      70% N(2)O in oxygen with 100% response (high-responders); and male and female
      F(2) mice responding with 0% response (low-responders). Genomic DNA was extracted
      from the spleens and genotyped with simple sequence length polymorphism MapPairs
      markers. Findings were combined with findings from the earlier QTL analysis from
      BXD recombinant inbred mice [Brain Res 725 (1996) 23]. Combined results revealed
      two significant QTL that influence responsiveness to nitrous oxide on proximal
      chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18.
      The chromosome 2 QTL was evident only in males. A significant interaction was
      found between a locus on chromosome 6 and another on chromosome 13 with a
      substantial effect on N(2)O antinociception.

PMID- 14706787
TI  - Neuronal expression of the drug efflux transporter P-glycoprotein in the rat
      hippocampus after limbic seizures.
AB  - In the brain, the efflux transporter P-glycoprotein (Pgp) is predominantly
      located on the luminal membrane of endothelial cells lining brain microvessels
      and forming the blood-brain barrier. Many lipophilic drugs, including
      antiepileptic drugs, are potential substrates for Pgp. Overexpression of Pgp in
      endothelial cells of the blood-brain barrier has been determined in patients with
      drug resistant forms of epilepsy such as temporal lobe epilepsy and rodent models
      of temporal lobe epilepsy and suggested to lead to reduced penetration of
      antiepileptic drugs into the brain. Expression of Pgp after seizures has also
      been described in astrocytes, whereas it is not clear whether neurons can express
      Pgp. In the present study, Pgp expression was studied by immunohistochemistry in
      rats 24 h after a status epilepticus induced by either pilocarpine or kainate,
      widely used models of temporal lobe epilepsy. Unexpectedly, in addition to
      endothelial Pgp staining, intense Pgp staining was found in neurons in the
      CA3c/CA4 sectors and hilus of the hippocampus formation, but not in other brain
      regions examined. The neuronal Pgp staining was confirmed by two different Pgp
      antibodies. Double immunolabeling and confocal microscopy showed that Pgp was
      colocalized with the neuronal marker neuronal nuclear antigen, but not with the
      glial marker glial fibrillary acidic protein. No neuronal Pgp staining was seen
      in control rats. The expression of Pgp in neurons after limbic seizures was
      substantiated by determining Pgp encoding genes (mdr1a, mdr1b) in neurons by real
      time quantitative RT-PCR. Increased Pgp expression in hippocampal neurons is
      likely to affect the action of drugs with intraneuronal targets and, in view of
      recent evidence from other cell types, could be associated with prevention of
      apoptosis which is involved in neuronal damage developing after seizures such as
      produced by pilocarpine.

PMID- 14706788
TI  - Differential co-localisation of the P2X7 receptor subunit with vesicular
      glutamate transporters VGLUT1 and VGLUT2 in rat CNS.
AB  - Presynaptic P2X(7) receptors are thought to play a role in the modulation of
      transmitter release and have been localised to terminals with the location and
      morphology typical of excitatory boutons. To test the hypothesis that this
      receptor is preferentially associated with excitatory terminals we combined
      immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two
      vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This
      confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic
      terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR
      depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised
      with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR
      was widespread, but co-localisation with VGLUT1-IR was seen only in the external
      cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the
      cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the
      granular layer. In the hippocampus it was co-localised only with VGLUT1-IR,
      including in the polymorphic layer of the dentate gyrus and the substantia
      radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised
      with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular
      thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate
      nucleus, amygdala and hypothalamus. Dual labelling studies performed using
      markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals
      indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also
      expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals.
      These data support our previous hypothesis that the P2X(7)R may play a role in
      modulating glutamate release in functionally different systems throughout the CNS
      but further suggest a role in modulating release of inhibitory transmitters in
      some regions.

PMID- 14706789
TI  - Increased expression of Ca2+/calmodulin-dependent protein kinase II alpha during
      chronic morphine exposure.
AB  - The chronic administration of morphine and related opioid drugs results in
      tolerance and dependence which limits the clinical utility of these agents.
      Neuronal plasticity is probably responsible in large part for tolerance and
      dependence. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a
      crucial role in the neuroplastic events underlying memory formation and other
      phenomena. However, the role of this kinase in morphine tolerance remains
      unclear. To clarify this issue we explored mRNA and protein expression of
      CaMKIIalpha in spinal cord tissue from control and morphine treated mice using
      real-time polymerase chain reaction, Western blot analysis and confocal
      microscopy. Our chronic exposure paradigm involved the subcutaneous implantation
      of morphine pellets for 6 days prior to tissue analysis. The results indicate
      that the levels of CaMKIIalpha mRNA and protein were robustly increased in spinal
      cord tissue from morphine-treated mice. Confocal microscopy demonstrated that the
      increase in CaMKIIalpha expression was primarily localized to superficial laminae
      of the dorsal horn. In addition, the abundance of phosphorylated CaMKIIalpha was
      increased in spinal cord tissue from morphine-treated mice. We conclude that
      enhanced CaMKIIalpha expression and activity in spinal cord tissue may contribute
      to the development of morphine tolerance in mice. The involvement of this enzyme
      in opioid tolerance suggests other parallels may exist between the neuroplastic
      events related to memory formation and those related to opioid tolerance or pain.

PMID- 14706790
TI  - Central terminals of nociceptors are targets for nicotine suppression of
      inflammation.
AB  - Spinal intrathecal administration of nicotine inhibits bradykinin-induced plasma
      extravasation, a component of the inflammatory response, in the knee joint of the
      rat in a dose-related fashion. Nociceptors contain nicotinic receptors and
      activation of a nociceptor at its peripheral terminal, by capsaicin, also
      produces inhibition of inflammation. Therefore the aim of this study was to test
      the hypothesis that the spinal target for this effect of nicotine is the central
      terminal of the primary afferent nociceptor. Intrathecal administration of the
      neurokinin-1 receptor antagonist, (3aR,7aR)-7,7-diphenyl-2-(1-imino-2(2
      methoxyphenyl)-ethyl) perhydroisoindol-4-1 hydrochloride or the N-methyl-D
      aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid, both
      antagonists of the action of primary afferent neurotransmitters, markedly
      attenuated the inhibition of bradykinin-induced plasma extravasation produced by
      both intrathecal nicotine and intraplantar capsaicin.Conversely, intrathecal
      administration of an alpha-adrenoceptor antagonist, phentolamine or an opioid
      receptor antagonist, naloxone, to block descending antinociceptive controls,
      which provide inhibitory input to primary afferent nociceptors, enhanced the
      action of both nicotine and capsaicin. These findings support the hypothesis that
      the central terminal of the primary afferent nociceptor is a CNS target at which
      nicotine acts to inhibit inflammation.

PMID- 14706791
TI  - Cortical acetylcholine release and electroencephalogram activation evoked by
      ionotropic glutamate receptor agonists in the rat basal forebrain.
AB  - To determine the sensitivity of basal forebrain cholinergic neurons to ionotropic
      glutamate receptor activation, acetylcholine was collected from the cerebral
      cortex of urethane-anesthetized rats using microdialysis while monitoring
      cortical electroencephalographic (EEG) activity. alpha-Amino-3-hydroxy-5
      methylisoxazole-4-proprionic acid (AMPA; 1, 10, or 100 microM), N-methyl-D
      aspartate (NMDA; 100 or 1000 microM) or a combination of AMPA (10 microM) and
      NMDA (100 microM) was administered to the basal forebrain using reverse
      microdialysis. Both glutamate receptor agonists produced concentration-dependent,
      several-fold increases in acetylcholine release indicating that they activated
      basal forebrain cholinergic neurons; AMPA was more potent, increasing
      acetylcholine release at a lower concentration than NMDA. The combination of AMPA
      and NMDA did not produce any greater release than each drug alone, indicating
      that the effects of these two drugs on cholinergic neurons are not additive. EEG
      was analyzed by fast Fourier transforms to determine the extent of physiological
      activation of the cortex. The highest concentrations of AMPA and NMDA tested
      produced small (25%) but significant increases in high frequency activity. There
      was a positive correlation across animals between the increases in power in the
      beta (14-30 Hz) and gamma (30-58 Hz) ranges and increases in acetylcholine
      release. These results indicate that glutamate can activate cholinergic basal
      forebrain neurons via both AMPA and NMDA ionotropic receptors but has a more
      modest effect on EEG activation.

PMID- 14706792
TI  - Neurons in the principal nucleus of the bed nuclei of the stria terminalis
      provide a sexually dimorphic GABAergic input to the anteroventral periventricular
      nucleus of the hypothalamus.
AB  - Neurons of the principal nucleus of the bed nuclei of the stria terminalis (BSTp)
      process pheromonal and viscerosensory stimuli associated with reproduction and
      relay this information to preoptic and hypothalamic cell groups that regulate
      reproductive function. The anteroventral periventricular nucleus of the
      hypothalamus (AVPV), a nucleus involved in the regulation of gonadotropin
      secretory patterns, receives dense projections from BSTp neurons in males but not
      in females. By injecting the anterograde tracer, Phaseolus vulgaris
      leucoagglutinin (PHAL), into the BSTp of rats and immunohistochemically
      colocalizing the GABA synthetic enzyme, GAD65, to PHAL-immunoreactive fibers in
      the AVPV, we tested the hypothesis that these sex-specific projections arise from
      BSTp neurons that synthesize the inhibitory neurotransmitter GABA. Although dense
      GAD65-immunoreactive fiber terminals were observed in both the male and female
      AVPV, higher numbers of GAD65-labeled terminals were found in the male, and those
      localized to PHAL-immunoreactive fibers were seen almost exclusively in males.
      Treatment of newborn females with testosterone or neonatal orchidectomy of males
      reversed these sex differences, while GAD65-immunoreactivity in the AVPV was not
      altered in response to exogenous hormone treatments administered to peripubertal
      animals. Our results suggest that projections from BSTp neurons constitute a
      stable, sex-specific GABAergic input to the AVPV that is patterned permanently by
      perinatal hormone exposure.

PMID- 14706794
TI  - Influence of illuminating and viewing aperture size on the color of dental resin
      composites.
AB  - OBJECTIVES: The objective was to evaluate the difference in the color of dental
      resin composites by the illuminating and viewing aperture sizes. The influences
      of the color measuring geometry, standard illumination and surface roughness on
      the color were also determined. METHODS: Color of five brands of resin composites
      of A2 shade was measured after-polymerization and after-polishing. Color was
      measured according to the CIE L(*)a(*)b(*) color scale with the SCE and SCI
      geometry under the CIE standard illumination of A and D65. The
      illuminating/viewing aperture sizes were 11 mm/8 mm (8 mm) and 3 mm/3 mm (3 mm).
      RESULTS: Regardless of the measuring geometry, CIE L(*), a(*) and b(*) values
      measured at 3 mm were lower than those at 8 mm. Changes in L(*), a(*) and b(*)
      values by the difference in the aperture size were 17.22-21.32, 3.43-6.64 and
      13.82-16.81, respectively, and the color difference (DeltaE(*)) was 16.23-27.87
      with the SCE geometry. Regardless of the aperture size, DeltaE(*) values caused
      by polishing measured with the SCE were significantly higher than those with the
      SCI. SIGNIFICANCE: Aperture size, measuring geometry and surface conditions of
      specimen should be considered when comparing the result of color measurement.

PMID- 14706793
TI  - Effects of the acetone content of single solution dentin bonding agents on the
      adhesive layer thickness and the microtensile bond strength.
AB  - OBJECTIVES: This study investigated the hypothesis that varying the acetone
      content of single solution dentin bonding agents may affect the adhesive layer
      thickness and microtensile bond strength (MTBS) of the bonded complex, and
      explored whether the adhesive layer thickness is a valid predictor for MTBS.
      METHODS: Experimental dentin bonding agents containing (27, 37, 47, 57, or 67)
      mass fraction% acetone were used to bond composite resin onto occlusal dentin
      surfaces of extracted human molars. The adhesive layer thickness was determined
      by digitized image analysis. MTBS was measured after 48 h. The fracture surfaces
      were observed using SEM. RESULTS: With increasing acetone content, MTBS varied
      from 38 MPa (67% acetone) to the highest MTBS of 64 MPa (37% acetone), while the
      adhesive layer thickness decreased linearly. Both dependent variables
      demonstrated moderate inverse correlation with the acetone content (p<0.0001),
      but were not correlated with each other (p>0.05). Ninety-four percent of the
      specimens showed fractures within the adhesive layer extending toward the
      interfaces with the hybrid layer or the composite resin. In the groups containing
      57 and 67% acetone, cracks were observed at these interfaces. SIGNIFICANCE:
      Rather than the adhesive layer thickness, interfacial cracks in specimens with
      acetone-rich bonding agents may have caused lower MTBS. Within the scope of this
      investigation, lower acetone concentrations, as could be anticipated from solvent
      evaporation during clinical use of the bonding agent, did not seem to lower MTBS,
      but rather improved the integrity of the dentin/adhesive bond.

PMID- 14706795
TI  - An evaluation of the surface changes in PMMA biomaterial formulations as a result
      of toothbrush/dentifrice abrasion.
AB  - OBJECTIVES: The objective of this study was to evaluate the abrasion resistance
      and surface roughness of two injection-molded poly(methylmethacrylate) denture
      base materials (SR-Ivocap 'Plus', Ipsyl 60 RV), and also one compression-molded
      material (Trevalon). A fourth group of specimens (prepared from Trevalon using
      the injection-molding procedure) was compared to the compression-molded
      specimens. METHODS: Ten specimens were prepared according to manufacturers'
      instructions. An experiment involving toothbrush and dentifrice abrasion was
      performed on all specimens from each of the materials and the cumulative
      percentage weight-loss was calculated after 100,000 brush strokes. A series of
      surface roughness profile measurements were also obtained from each specimen
      within the groups. The data were analysed by using the Kolmogorov-Smirnov test. A
      level of significance of 0.017 was set in order to adjust for multiple
      comparisons between the three sets of materials. RESULTS: There was found to be
      no statistically significant difference between the three groups of materials in
      terms of percentage weight-loss, and no statistically significant difference
      between the Trevalon specimens when injection-molded or compression-molded. In
      terms of surface roughness, however, SR-Ivocap 'Plus' recorded the lowest surface
      roughness profile of the three groups. It was found that there was a
      statistically significant difference (P<0.017) between this material and Ipsyl RV
      60 (producing the highest roughness), and compression-molded Trevalon.
      Furthermore, there was found to be no statistically significant difference
      between injection-molded and compression-molded specimens of Trevalon with regard
      to surface texture. SIGNIFICANCE: From a clinical standpoint, the surface
      roughness results suggest SR-Ivocap 'Plus' to be the material most likely to
      produce the least suitable substrate for the accumulation of denture plaque.

PMID- 14706796
TI  - Morphology and properties of denture acrylic resins cured by microwave energy and
      conventional water bath.
AB  - OBJECTIVES: This study examined the influence of microwave energy levels on the
      morphology and properties of an impact resistant denture material poly(methyl
      methacrylate) with a thickness of 10 mm. METHODS: A microwave flask containing
      two resin blocks was processed at 80, 160, 240, and 560 W for 15, 10, 7, and 2
      min, separately. Each Flask was then turned over, and cured for an additional 2
      min at 560 W. The process using conventional methods was carried out at 70
      degrees C for 9 h. The blocks were tested for hardness, porosity, flexural
      properties, solubility, and molecular weight. The morphology of the specimens
      after staining with osmium tetroxide was examined by transmission electron
      microscope. RESULTS: The changes in temperature with time were recorded during
      microwave heating at 80, 160, and 240 W, respectively. A significantly large
      difference in the curing temperature was observed when comparing these two
      processing methods. There was little difference in the mean values of surface
      hardness and the weight percent of the insoluble parts. The mean domain size and
      the volume fraction of the rubber phase favor of the water-bath method. However,
      the porosity in the water-bath-cured specimens was much less than that in the
      microwave-cured specimens. Thus, the conventionally cured specimens showed better
      flexural strength and flexural modulus than the microwave-cured specimens.
      SIGNIFICANCE: This study has shown that microwave energy can efficiently
      polymerize denture base polymer. Highly statistical differences in morphology and
      flexural properties favor of the water-bath method. Choice of a suitable
      microwave power and polymerization time is important in order to reduce porosity
      to a minimum level and increase the domain size and volume of the rubber phase.

PMID- 14706797
TI  - The influence of interfacial surface roughness on bilayered ceramic specimen
      performance.
AB  - OBJECTIVES: The aim of the current study was to assess the influence of
      interfacial surface roughness on the performance of bilayered ceramic composite
      disc-shaped specimens. METHODS: Specific surface flaw distributions were
      introduced to a series of standard aluminous core porcelain disc specimens (12 mm
      diameter, 1.7 mm thickness) prior to bilayering with dentin porcelain. Mean
      flexure strengths, standard deviations and associated Weibull moduli (m) were
      determined using bi-axial flexure (ball-on-ring) for each series of 30 bilayered
      specimens. RESULTS: The mean bi-axial fracture strengths of bilayered specimens
      resulted in significant differences between specimen groups with the smoothest
      interfacial roughness recording the highest strength and fracture strength
      reliability. Specimen delamination was identified in five of the bilayered group
      with the smoothest interfacial roughness compared with no specimen delaminations
      in the rougher interface groups. However, fracture occurred in the weaker dentin
      layer rather than along the interface between the dentin and core porcelain for
      specimens in these rougher interface groups. CONCLUSIONS: A smoother interfacial
      surface roughness resulted in increased performance, namely increased strength
      and reliability amongst the bilayered dental ceramic composite specimens examined
      in the current investigation. The incidence of complete or partial delamination
      of the reinforcing core and aesthetic dentin was increased for these specimens
      since the reduced tortuosity of the interface between porcelain layers fails to
      restrict propagation of a crack front along the interface.

PMID- 14706798
TI  - Biological effects of blue light from dental curing units.
AB  - OBJECTIVES: This study assessed the effects of three common dental photo-curing
      light sources (quartz-tungsten-halogen (QTH), plasma-arc (PAC), and laser) on the
      cellular function of fibroblasts in vitro. METHODS: Mouse fibroblasts were
      exposed to light from dental photo-curing units for clinically relevant
      durations, with total energy exposures ranging from 1.3 to 60 J/cm(2). The
      temperature rise of the cell-culture medium was measured to assess any possible
      effect from temperature increases, and cellular function was assessed by succinic
      dehydrogenase (SDH) activity of mitochondria. To directly compare the three light
      sources, additional experiments were done using equivalent total energy exposures
      from each source by adjusting the exposure durations for each unit. RESULTS: In
      experiments that used clinically relevant exposure durations for each light,
      exposures ranging from 5 J/cm(2) (laser) to 15 J/cm(2) (PAC, QTH) irreversibly
      suppressed SDH activity nearly 100% when compared to no-light controls up to 72 h
      post-exposure. For the PAC and QTH sources, exposures as low as 3.5 J/cm(2) also
      irreversibly suppressed SDH activity. When equivalent energies were used from
      each light source, exposures of 1 J/cm(2) did not suppress SDH activity for the
      QTH and laser sources, but significantly (50%) suppressed SDH for the PAC source,
      indicating a difference in the biological effects of the outputs of the different
      curing units. Equivalent energy exposure experiments also indicated a definite
      dependence of SDH activity on the total light energy of exposure. Temperature
      rises ranged from 2 to 9 degrees C, and elevated temperatures lasted for 60-300 s
      above the base temperature of 37 degrees C, but peak temperature and the duration
      of temperature elevation were not always related and depended on the light source
      used. SIGNIFICANCE: Results from the current study indicate that these photo
      curing sources pose some risk of disrupting cellular function in vivo. Further
      study is necessary in other cell types and under more clinically relevant
      conditions to estimate the in vivo risk of photo-curing to oral tissues.

PMID- 14706799
TI  - Statistical estimation of resin composite polymerization sufficiency using
      microhardness.
AB  - With respect to determining sub-surface resin polymerization sufficiency, this
      study compared a traditional method of applying linear regression to bottom- to
      top-surface Knoop hardness ratios to an alternative method based on nonlinear
      regression. Inverse linear regression on ratios was used to estimate the exposure
      duration required for 80% bottom-surface hardness with respect to the top, in six
      light-by-material groups. Alternatively, a one-phase, two-parameter, exponential
      association of the form Y=Y(max)(1-e(-kt)) (where Y(max) is maximum hardness, k
      is a rate constant, and t is exposure duration), was used to model hardness.
      Inverse nonlinear regression estimated, for each condition, the exposure duration
      required for the bottom surface to achieve 80% of corresponding condition (light
      and material) top-surface Y(max). Mathematically, analysis of ratios was
      demonstrated to yield potentially less precise and biased estimates. Nonlinear
      regression yielded better statistical fit and provided easily accessible tests
      for differences in k across light-system groups. Another recently proposed
      nonlinear model for polymerization, Y=Y(max)kt(n)/(1+kt(n)), was also considered.
      While this new model has substantially greater phenomenological and mechanistic
      justification, we found that the model-fitting process was more sensitive to
      initial parameter values and sometimes yielded untenable results when applied to
      our data. However, we believe that these problems would not occur if sample
      points are well distributed across a wide range of exposure durations, and that
      the model, Y=Y(max)kt(n)/(1+kt(n)), should be considered for such data sets.

PMID- 14706800
TI  - Colonization and penetration of denture soft lining materials by Candida
      albicans.
AB  - OBJECTIVES: Colonization of denture soft lining materials by Candida albicans can
      result in clinical problems, and deterioration of the material. This study aimed
      to monitor this interaction by comparing the short-term adhesion of C. albicans
      to six denture lining materials and to monitor any longer term penetration of
      material by the yeast. METHODS: Denture lining materials (Molloplast B, Flexor,
      Permaflex, Luci-soft, Eversoft and Ufi Gel hard C) were processed against glass
      slides or dental stone. Adhesion of yeast to surfaces was monitored after one
      hour incubation (37 degrees C) of standardized (2.8 x 10(6) cfu/ml) washed cell
      suspension with test materials. Attached cells stained with acridine orange were
      counted microscopically. Penetration of yeast into materials bonded onto acrylic
      after six weeks incubation (culture medium was replaced weekly) was observed
      through sections stained using acridine orange. Hyphal and yeast penetration was
      estimated (qualitatively and quantitatively, respectively) for three levels of
      the liner (subsurface, central section and adjacent to lining-acrylic junction).
      RESULTS: None of the materials produced a zone of inhibition when compared with
      the nystatin control. There was no significant difference (p>0.5) in cell numbers
      on any of the smooth surfaces. Significantly, (p<0.001) higher numbers of cells
      were observed on roughened surfaces. Both hyphal and yeast forms were observed
      when penetration was monitored. Penetration was greatest into Ufi Gel hard C (no
      hyphae observed), but not at the acrylic-liner junction and least into Eversoft.
      SIGNIFICANCE: Different denture lining materials exhibit different properties in
      terms of susceptibility to yeast penetration, although the initial attachment is
      comparable. Smoother surfaces retain fewer cells. The selection of appropriate
      materials for a given function, and their fabrication may affect performance.

PMID- 14706801
TI  - Micromorphology of the fiber post-resin core unit: a scanning electron microscopy
      evaluation.
AB  - OBJECTIVES: [corrected] To microscopically evaluate the structural
      characteristics of post-and-core units made with a fiber post and different types
      of composite resins used as build-up materials. MATERIALS AND METHODS: Forty
      endodontically treated human maxillary incisors were prepared for receiving a
      fiber post (Aesthetic Post Plus, RTD). One-Step (Bisco) was used as a bonding
      material, and C&B resin cement (Bisco) for luting the post. The posted roots were
      randomly divided into eight groups. In each group a different material or
      technique was applied to build up the abutment. The materials on trial were Z100
      (3M-ESPE), Lumiglass (RTD), Gradia (GC), Build-it! (Jeneric Pentron). On the
      specimens of Groups 5-8, the same materials were used for build-ups, with the
      addition of a preshaped plastic shell (Composipost, Core Form, RTD). All the post
      and-core specimens were cut perpendicular to their long axis and processed for
      SEM observation. The objective was to detect the presence of voids/bubbles within
      the resin abutment, and of gaps at the interface between the post surface and the
      core material. These aspects were quantified with reference to indexes. The
      differences among the scores were tested for statistical significance (p<0.05).
      RESULTS: In the absence of any matrix, cores built up with Gradia showed the
      highest integrity, and those made with Z100 the best adaptation onto the post. In
      the presence of shells, Build-it! provided the most satisfactory result. Build
      it! was the only material to perform better when used in combination with a
      shell. SIGNIFICANCE: When hybrid composites are used to build up a core onto a
      fiber post, a higher homogeneity of the abutment and a better post-core
      integration are achieved if the build up is done in the absence of any matrix.

PMID- 14706802
TI  - Effects of blood contamination on resin-resin bond strength.
AB  - OBJECTIVE: Incremental placement and curing of resin composites has been
      recommended. However, this requires longer operating time, and therefore,
      increased risk of contamination. The purpose of this study was to evaluate the
      effects of blood contamination on microtensile bond strengths (microTBS) between
      resin interfaces and to determine the best decontamination method to re-establish
      the original resin-resin bond strength. MATERIALS: The top surfaces of 64, 4-mm
      composite blocks (Z-250, Renew, APX, Pertac II) were untreated as the control, or
      were treated as follows: blood applied and dried on the surface (Treatment 1),
      blood applied, rinsed, dried (Treatment 2), blood applied, rinsed, and an
      adhesive applied (Single Bond, One-Step, Clearfil SE, Prompt L-Pop) (Treatment
      3). Fresh composite was applied and light-cured in 2-mm increments. After 24 h
      storage in water, the specimens were sectioned into 0.7-mm thick slabs, trimmed
      to a cross-sectional area of 1 mm(2), and loaded to failure at a crosshead speed
      of 1 mm/min using an Instron universal testing machine. Data were analyzed using
      two-way ANOVA and Fisher's PLSD test (p<0.05). RESULTS: Control values ranged
      from 45.1 MPa for Pertac II to 71.5 MPa for APX. Untreated blood contamination
      resulted in resin-resin bond strengths of only 1.0-13.1 MPa. Rinsing raised bond
      strengths to over 40 MPa for each material. Use of an adhesive further increased
      bond strengths except for Pertac II. SIGNIFICANCE: Rinsing blood from
      contaminated surfaces increases the resin-resin bond strength significantly and
      the application of an appropriate adhesive increases the bond strength to control
      levels.

PMID- 14706803
TI  - Marginal adaptation in dentin of a self-adhesive universal resin cement compared
      with well-tried systems.
AB  - OBJECTIVES: This study compares the marginal adaptation of a new self-adhesive
      universal resin cement with only one application step, to the marginal adaptation
      of established cements and their corresponding adhesive systems. METHODS: All
      ceramic crowns were inserted on human molars using a new self-adhesive universal
      resin cement without and with one pre-treatment step, a resin cement with a smear
      layer removing and a compomer cement with a smear-layer dissolving adhesive
      system. After simulation of five years oral stress, the marginal adaptation was
      evaluated by dye penetration and scanning electronic microscope analysis using
      the replica technique. RESULTS: Scanning electron microscopy: all investigated
      luting agents showed comparable amounts of 'perfect margin' ranging between 88
      98% (median). Dye penetration: the self-adhesive system had significantly lower
      dye penetration (18-25%, median). SIGNIFICANCE: The results indicate that a self
      adhesive universal resin cement without pre-treatment can provide a marginal
      adaptation at dentin which is comparable to established luting agents.

PMID- 14706804
TI  - Indentation fracture toughness and dynamic elastic moduli for commercial
      feldspathic dental porcelain materials.
AB  - OBJECTIVE: The purpose of this study was to evaluate and compare the indentation
      fracture toughness, true hardness and dynamic elastic moduli for 14 commercial
      dental porcelain materials. METHODS: The specimens were fired according to
      manufacturer instructions. The density of the specimens (n=3) was measured by
      means of the water displacement technique. Dynamic Young's shear and bulk moduli
      and Poisson's ratio (n=3) were measured using a non-destructive ultrasonic
      technique using 10 MHz lithium niobate crystals. The true hardness (n=3) was
      measured using a Knoop indenter and the fracture toughness (n=3) was determined
      using a Vickers indenter and a Tukon hardness tester. Statistical analysis of the
      data was conducted using ANOVA and a Student-Newman-Keuls (SNK) rank order
      multiple comparative test. RESULTS: The SNK rank test analysis for the mean
      dynamic Young's modulus and fracture toughness was able to separate 14 dental
      porcelain materials into seven and nine groups, respectively, at p=0.05. The
      elastic moduli, true hardness and indentation fracture toughness for opaque
      porcelains were significantly higher than incisal; and body materials at p=0.05.
      SIGNIFICANCE: The indentation fracture toughness and the ultrasonic test methods
      exhibit lower coefficient of variation compared to conventional methods and have
      considerable advantage for ceramic dental materials in that only small specimens
      are required to produce an acceptable number of data for statistical analysis.

PMID- 14706805
TI  - Mechanical properties of commercial high strength ceramic core materials.
AB  - OBJECTIVE: The objective of the present study is to evaluate and compare the
      flexural strength, dynamic elastic moduli and true hardness (H(o)) values of
      commercial Vita In-Ceram alumina core and Vita In-Ceram matrix glass with the
      standard aluminous porcelain (Hi-Ceram and Vitadur), Vitadur N and Dicor glass
      and glass-ceramic. METHODS: The flexural strength was evaluated (n=5) using 3
      point loading and a servo hydraulic Instron testing machine at a cross head speed
      of 0.5 mm/min. The density of the specimens (n=3) was measured by means of the
      water displacement technique. Dynamic Young's shear and bulk moduli and Poisson's
      ratio (n=3) were measured using a non-destructive ultrasonic technique using 10
      MHz lithium niobate crystals. The true hardness (n=3) was measured using a Knoop
      indenter and the fracture toughness (n=3) was determined using a Vickers indenter
      and a Tukon hardness tester. Statistical analysis of the data was conducted using
      ANOVA and a Student-Newman-Keuls (SNK) rank order multiple comparative test.
      RESULTS: The SNK rank order test analysis of the mean flexural strength was able
      to separate five commercial core materials into three significant groups at
      p=0.05. Vita In-Ceram alumina and IPS Empress 2 exhibited significantly higher
      flexural strength than aluminous porcelains and IPS Empress at p=0.05. The
      dynamic elastic moduli and true hardness of Vita In-Ceram alumina core were
      significantly higher than the rest of the commercial ceramic core materials at
      p=0.05. SIGNIFICANCE: The ultrasonic test method is a valuable mechanical
      characterization tool and was able to statistically discriminate between the
      chemical and structural differences within dental ceramic materials. Significant
      correlation was obtained between the dynamic Young's modulus and true hardness,
      p=0.05.

PMID- 14706808
TI  - Intestinal solute carriers: an overview of trends and strategies for improving
      oral drug absorption.
AB  - A large amount of absorptive intestinal membrane transporters play an important
      part in absorption and distribution of several nutrients, drugs and prodrugs. The
      present paper gives a general overview on intestinal solute carriers as well as
      on trends and strategies for targeting drugs and/or prodrugs to these carriers in
      order to increasing oral bioavailability and distribution. A number of absorptive
      intestinal transporters are described in terms of gene and protein
      classification, driving forces, substrate specificities and cellular
      localization. When targeting absorptive large capacity membrane transporters in
      the small intestine in order to increase oral bioavailabilities of drug or
      prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose
      dependent increase in bioavailability as well as prolonged blood circulation due
      to large capacity facilitated absorption, and renal re-absorption, respectively.
      In contrast, when targeting low-capacity transporters such as vitamin
      transporters, dose independent saturable absorption kinetics are suggested. We
      thus believe that targeting drug substrates for absorptive intestinal membrane
      transporters could be a feasible strategy for optimizing drug bioavailability and
      distribution.

PMID- 14706809
TI  - Intestinal membrane transport of drugs and nutrients: genomics of membrane
      transporters using expression microarrays.
AB  - Carrier-mediated transport across membranes plays an important role in drug and
      nutrient absorption. However, relevant transporters remain largely unknown for
      most substrates. Their identification requires global analysis of expressed mRNAs
      in intestinal tissues. Microarray technologies capable of measuring mRNA profiles
      have proven useful in detecting the expression of genes encoding transporters and
      ion channels in intestines and Caco-2 cells. This colon carcinoma cell line with
      characteristics of absorptive enterocytes serves as a common model for drug
      absorption studies. Gene expression patterns of membrane transporters and
      channels define the cell's overall transport capacity. Moreover, transporter mRNA
      profiles provide a basis for assessing drug-drug and drug-food interactions in
      intestinal absorption. To determine relevant transporters for any given
      substrate, chemogenomic methods have emerged correlating mRNA expression in
      multiple tissues to drug transport or response. The resultant drug-transporter
      databases permit the search for transporter-drug relationships at a genomic
      scale.

PMID- 14706810
TI  - The ABCs of drug transport in intestine and liver: efflux proteins limiting drug
      absorption and bioavailability.
AB  - Many orally administered drugs must overcome several barriers before reaching
      their target site. The first major obstacle to cross is the intestinal
      epithelium. Although lipophilic compounds may readily diffuse across the apical
      plasma membrane, their subsequent passage across the basolateral membrane and
      into blood is by no means guaranteed. Efflux proteins located at the apical
      membrane, which include P-glycoprotein (Pgp; MDR1) and MRP2, may drive compounds
      from inside the cell back into the intestinal lumen, preventing their absorption
      into blood. Drugs may also be modified by intracellular phase I and phase II
      metabolising enzymes. This process may not only render the drug ineffective, but
      it may also produce metabolites that are themselves substrates for Pgp and/or
      MRP2. Drugs that reach the blood are then passed to the liver, where they are
      subject to further metabolism and biliary excretion, often by a similar system of
      ATP-binding cassette (ABC) transporters and enzymes to that present in the
      intestine. Thus a synergistic relationship exists between intestinal drug
      metabolising enzymes and apical efflux transporters, a partnership that proves to
      be a critical determinant of oral bioavailability. The effectiveness of this
      system is optimised through dynamic regulation of transporter and enzyme
      expression; tissues have a remarkable capacity to regulate the amounts of protein
      both at transcriptional and post-transcriptional levels in order to maintain
      homeostasis. This review addresses the progress to date on what is known about
      the role and regulation of drug efflux mechanisms in the intestine and liver.

PMID- 14706811
TI  - The intestinal H+/peptide symporter PEPT1: structure-affinity relationships.
AB  - Peptide transporter 1, PEPT1, of the mammalian enterocyte is presently under
      intense investigation in many laboratories because of its nutritional importance
      in the absorption of protein hydrolysis products and because more recent studies
      have shown that many drugs and prodrugs gain entry into the systemic circulation
      via PEPT1. Until the exact structural features of the substrate binding site of
      PEPT1 become available, for example by X-ray crystallography, determination of
      affinities followed by proof of actual membrane translocation will have to
      suffice when testing for possible new substrates for PEPT1. Affinity constants
      reflect the strength of their interaction with the binding site of the
      transporter. A review of the literature shows a wide range of affinity constants
      between 2 microM and 30 mM. We consider affinity constants for substrates or
      inhibitors of PEPT1 lower than 0.5 mM as high affinity, between 0.5 and 5.0 mM as
      medium affinity and above 5 mM as low affinity. Values above 15 mM we consider
      with great caution. In this mini-review we discuss affinities and structural
      determinants which affect affinities of a variety of substrates for PEPT1.

PMID- 14706812
TI  - Analysis of the transport properties of side chain modified dipeptides at the
      mammalian peptide transporter PEPT1.
AB  - This study was initiated to examine systematically the effect of side chain
      modifications at dipeptides on their transport via PEPT1. We synthesized a series
      of Xaa(R)-Ala and Ala-Xaa(R) dipeptides with the functional groups of the side
      chains modified by structurally different blocking groups R. Recognition and
      transport of these derivatives by PEPT1 was measured in Caco-2 cells, in
      transgenic Pichia pastoris cells and in Xenopus laevis oocytes expressing PEPT1.
      The dipeptide derivatives displayed K(i) values between 0.002 and 4 mM.
      Electrophysiological analyses showed that the Ala-Xaa(R) derivatives were
      transported by PEPT1. In contrast, most Xaa(R)-Ala derivatives--although
      recognized--did not show significant transport rates. Substitution of a terminal
      phenyl residue in the side chain blocking group by a p-nitrophenyl residue
      enhanced the affinity of several dipeptide derivatives for interaction with
      PEPT1. However, none of these compounds showed electrogenic transport in oocytes.
      With a K(i) value of 0.002 mM, Lys[Z(NO(2))]-Val displayed the highest affinity
      to PEPT1 ever reported. We conclude that the transport of side chain modified
      dipeptides into enterocytes depends (a) on the position of the modified
      trifunctional amino acid in the dipeptide, (b) the distance between its alpha
      carbon and the side chain blocking group and (c) the hydrophobic character of the
      side chain modification.

PMID- 14706813
TI  - Exploring the quantitative relationship between the level of MDR1 transcript,
      protein and function using digoxin as a marker of MDR1-dependent drug efflux
      activity.
AB  - A limited number of gene expression studies have investigated the quantitative
      relationships between the amount of transcript, level of protein or
      activity/function, with disparate conclusions regarding these relationships.
      Collectively these studies indicate that the relevance of quantitative transcript
      analysis as a predictor of phenotype has to be evaluated on a gene-by-gene or
      even a case-by-case basis. The purpose of this study was to define a suitable
      marker for MDR1-dependent drug efflux, and to quantitatively investigate the
      relationships between the amount of transcript, protein and drug efflux in the
      frequently used Caco-2 cell model. The substrate specificity of digoxin, a
      commonly used marker for MDR1, was investigated using transgenic MDCK II or LLC
      PK1 cell lines expressing the efflux proteins MDR1, BCRP and MRP2, since these
      proteins are localised to the apical part of the enterocyte plasma membrane and
      exhibit comparatively high transcript levels in the human small intestine.
      Relationships between levels of transcript, protein and function were
      investigated quantitatively using real-time RT-PCR, ECL western blot analysis and
      basolateral-to-apical and apical-to-basolateral efflux ratios. Our results
      indicate that digoxin is a specific marker for MDR1-dependent drug efflux in the
      Caco-2 cell drug absorption model and that MDR1 transcript abundance is at least
      as valid as MDR1 protein abundance as a predictor of MDR1 efflux activity.

PMID- 14706814
TI  - In-depth evaluation of Gly-Sar transport parameters as a function of culture time
      in the Caco-2 cell model.
AB  - The aim of the present study was to investigate the influence of culture time on
      hPEPT1-mediated transport in Caco-2 cell monolayers. Peptide transport activity
      in Caco-2 cells grown in standard media and in a "rapid" 4-day model was first
      compared. The rapid 4-day Caco-2 cell model, cultured using a cocktail of growth
      factors and agonists, displayed lower peptide uptake capacity than Caco-2 cells
      grown for 4 days in conventional media, and was judged to be unsuitable for
      peptide transport studies. Peptide transport activity as well as monolayer
      integrity and tissue morphology were evaluated in the standard >21 days model as
      a function of the culture time. Peptide transport activity was studied using
      [14C]-glycylsarcosine ([14C]-Gly-Sar). Monolayer integrity was evaluated by
      transepithelial electrical resistance (TEER) measurements and [3H]-mannitol
      permeabilities. Tissue morphology and hPEPT1 expression were studied using
      confocal laser scanning microscopy (CLSM) and conventional
      staining/immunostaining. Caco-2 cells grown in conventional media became
      confluent after 3-4 days. Mannitol permeability decreased from day 5 to 21 and
      TEER increased steadily until approximately day 21. Apical hPEPT1 uptake activity
      appeared to be maximal in cells cultured for >21 days, whereas basolateral uptake
      reached a maximum already after 12 days in culture. In some of the passages
      studied, a secondary increase in hPEPT1 transport activity was observed in cells
      grown for >25 days. A large carrier-mediated transepithelial peptide flux
      component was evident from day 14.

PMID- 14706815
TI  - Effect of insulin on cephalexin uptake and transepithelial transport in the human
      intestinal cell line Caco-2.
AB  - We investigated whether cephalexin transport in Caco-2 cells is regulated by
      insulin. After the insulin pretreatment, cephalexin uptake, and transport as well
      as PEPT1 mRNA and protein expression in the cells were measured. Cephalexin
      uptake was significantly increased by the insulin pretreatment. Insulin
      significantly increased cephalexin saturable uptake, but had no significant
      effect on the non-saturable one. PEPT1 protein expression on the apical membrane,
      but not PEPT1 mRNA expression, was increased by the insulin pretreatment. The
      enhancement of cephalexin uptake by the insulin pretreatment was inhibited by
      genistein, a tyrosine kinase inhibitor, and colchicine, an agent that disrupts
      protein translocation. Apical-to-basolateral transport of cephalexin has
      increased by the insulin pretreatment at the apical side and long-term insulin
      pretreatment at the basolateral side. It is considered that insulin mainly binds
      to its receptor on the apical and basolateral membranes, thereby promoting PEPT1
      translocation from the intracellular pool to the apical membrane surface;
      consequently, PEPT1 protein expression on the apical membrane is increased.

PMID- 14706816
TI  - Recent developments in the analysis of protein complexes.
AB  - The goal of this review is to analyse how recent technical developments
      contributed to the biochemical characterisation of protein complexes. Improvement
      of tags used for protein purification, including in our own laboratory, and the
      development of new strategies have allowed the use of generic procedures for the
      purification of a wide variety of protein complexes. Together with increased mass
      spectrometry sensitivity and automation, this made high throughput studies of
      protein complexes possible and allowed proteome-wide analyses of protein
      complexes. However, knowledge of protein complex composition, even at the
      cellular level, will not be sufficient to understand their function. We suggest
      that the next level of analysis in this area will be the definition of internal
      subunit arrangement in complexes as a first step toward more detailed structural
      analyses.

PMID- 14706817
TI  - Results and prospects of the yeast three-hybrid system.
AB  - In 1996, a new method, termed the yeast three-hybrid system, dedicated to
      selection of RNA binding proteins using a hybrid RNA molecule as bait was
      described. In this minireview, we summarize the results that have been obtained
      using this method. Indeed, approximately 20 unknown proteins have been
      characterized so far. The three-hybrid strategy has also been used as a tool to
      dissect RNA-protein interactions. The example of such a study on human histone
      HBP interaction with its target mRNA is described. Problems that can be
      encountered are addressed in a troubleshooting section. Especially, our results
      with tRNA binding proteins are discussed.

PMID- 14706818
TI  - Agonist induction, conformational selection, and mutant receptors.
AB  - Current models of receptor activation are based on either of two basic
      mechanisms: agonist induction or conformational selection. The importance of one
      pathway relative to the other is controversial. In this article, the
      impossibility of distinguishing between the two mechanisms under a thermodynamic
      approach is shown. The effect of receptor mutation on the constants governing
      ligand-receptor equilibria is discussed. The two-state model of agonism both in
      its original formulation (one cycle) and including multiple active states
      (multiple cycles) is used. Pharmacological equations for the double (two cycles)
      two-state model are derived. The simulations performed suggest that the double
      two-state model of agonism can be a useful model for assessing quantitatively the
      changes in pharmacological activity following receptor mutation.

PMID- 14706819
TI  - The ubiquitin-proteasome pathway is required for the function of the viral VP16
      transcriptional activation domain.
AB  - The ability of the activation domain of specific protein factors to regulate
      transcription is intimately connected to their ubiquitin-mediated proteolysis.
      Here, we provide evidence that ubiquitin-proteasome function is required for a
      family of synthetic viral VP16 transcription activators in mammalian cells.
      Blocking the degradation of VP16 activators, through proteasome inhibitors or by
      disrupting the ubiquitylation function, severely compromises their
      transcriptional activity. Overexpression of SUG-1, a subunit of the proteasome,
      reduces both transactivation and degradation of VP16 activators. The inhibitory
      effect of SUG-1 overexpression is enhanced when a single non-removable ubiquitin
      moiety is fused to the amino-terminus of the VP16 activator. The 19S regulatory
      subunit of the proteasome physically associates with the general transcription
      factor TFIIH, indicating the direct involvement of the proteasome in
      transcription. These results support a model in which ubiquitin plays an
      accessory role, in recruiting the 19S regulatory subunit of the proteasome, for
      transcriptional activation.

PMID- 14706820
TI  - Engineering the serine/threonine protein kinase Raf-1 to utilise an orthogonal
      analogue of ATP substituted at the N6 position.
AB  - One key area of protein kinase research is the identification of cognate
      substrates. The search for substrates is hampered by problems in unambiguously
      assigning substrates to a particular kinase in vitro and in vivo. One solution to
      this impasse is to engineer the kinase of interest to accept an ATP analogue
      which is orthogonal (unable to fit into the ATP binding site) for the wild-type
      enzyme and the majority of other kinases. The acceptance of structurally
      modified, gamma-(32)P-labelled, nucleotide analogue by active site-modified
      kinase can provide a unique handle by which the direct substrates of any
      particular kinase can be displayed in crude mixtures or cell lysates. We have
      taken this approach with the serine/threonine kinase Raf-1, which plays an
      essential role in the transduction of stimuli through the Ras-->Raf-->MEK-
      >ERK/MAP kinase cascade. This cascade plays essential roles in proliferation,
      differentiation and apoptosis. Here we detail the mutagenesis strategy for the
      ATP binding pocket of Raf-1, such that it can utilise an N(6)-substituted ATP
      analogue. We show that these mutations do not alter the substrate specificity and
      signal transduction through Raf-1. We screen a library of analogues to identify
      which are orthogonal for Raf-1, and show that mutant Raf-1 can utilise the
      orthogonal analogue N(6)(2-phenethyl) ATP in vitro to phosphorylate its currently
      only accepted substrate MEK. Importantly we show that our approach can be used to
      tag putative direct substrates of Raf-1 kinase with (32)P-N(6)(2-phenethyl) ATP
      in cell lysates.

PMID- 14706821
TI  - Subunit A of the E. coli ATP synthase: reconstitution and high resolution NMR
      with protein purified in a mixed polarity solvent.
AB  - Subunit a of the Escherichia coli ATP synthase, a 30 kDa integral membrane
      protein, was purified to homogeneity by a novel procedure incorporating selective
      extraction into a monophasic mixture of chloroform, methanol and water, followed
      by Ni-NTA chromatography in the mixed solvent. Pure subunit a was reconstituted
      with subunits b and c and phospholipids to form a functional proton-translocating
      unit. Nuclear magnetic resonance (NMR) spectra of the pure subunit a in the mixed
      solvent show good chemical shift dispersion and demonstrate the potential of the
      solvent mixture for NMR studies of the large membrane proteins that are currently
      intractable in aqueous detergent solutions.

PMID- 14706822
TI  - Overexpression of redox factor-1 negatively regulates NO synthesis and apoptosis
      in LPS-stimulated RAW 264.7 macrophages.
AB  - Redox factor-1 (Ref-1) is a ubiquitously expressed protein with proven roles as a
      modulator of redox-sensitive transcription, and as an endonuclease in the base
      excision repair pathway of oxidatively damaged DNA. Although Ref-1 is induced by
      a variety of oxidative stress and protects cells against oxidative stress, the
      function of Ref-1 in regulating nitric oxide (NO) synthesis has not been
      elucidated to date. We investigated the role of Ref-1 in regulating NO synthesis
      and NO-mediated apoptosis employing adenoviral-mediated overexpression of Ref-1
      in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. LPS treatment
      produced NO synthesis and NO-mediated apoptosis. Forced overexpression of Ref-1
      suppressed LPS-stimulated NO synthesis. In parallel with this, Ref-1 also
      mitigated alteration of inducible NO synthase expression and NO-mediated
      apoptosis. Our findings suggest that Ref-1 is implicated in protection against
      cell death resulting from oxidative stimuli containing NO.

PMID- 14706823
TI  - Inhibitor-induced structural change of the active site of human poly(ADP-ribose)
      polymerase.
AB  - The crystal structure of human recombinant poly(ADP-ribose) polymerase (PARP)
      complexed with a potent inhibitor, FR257517, was solved at 3.0 A resolution. The
      fluorophenyl part of the inhibitor induces an amazing conformational change in
      the active site of PARP by motion of the side chain of the amino acid, Arg878,
      which forms the bottom of the active site. Consequently, a corn-shaped
      hydrophobic subsite, which consists of the side chains of Leu769, Ile879, Pro881,
      and the methylene chain of Arg878, newly emerges from the well-known active site.

PMID- 14706824
TI  - Disruption of gamma-glutamylcysteine synthetase results in absolute glutathione
      auxotrophy and apoptosis in Candida albicans.
AB  - Glutathione is the most abundant non-protein thiol and a major source of reducing
      equivalents in eukaryotes. We examined the role of glutathione in Candida
      albicans by the disruption of gamma-glutamylcysteine synthetase (GCS1), an
      essential enzyme in glutathione biosynthesis. The gcs1/gcs1 null mutants
      exhibited glutathione auxotrophy, which could be rescued by supplementing with
      reduced and oxidized glutathione and gamma-glutamylcysteine. When the mutants
      were depleted of glutathione, they showed typical markers of apoptosis. These
      results suggest that glutathione itself is an essential metabolite and C.
      albicans lacking GCS1 undergoes apoptosis.

PMID- 14706825
TI  - Identification of novel adrenomedullin in mammals: a potent cardiovascular and
      renal regulator.
AB  - We have identified cDNA encoding a new member of the adrenomedullin (AM) family,
      AM2, for the first time in mammals (mouse, rat and human). The predicted
      precursor carried mature AM2 in the C-terminus, which had an intramolecular ring
      formed by an S-S bond and a possibly amidated C-terminus. Phylogenetic analyses
      clustered AM2 and AM into two distinct but closely related groups. Similarity of
      exon-intron structure and synteny of neighboring genes showed that mammalian AM2
      is an ortholog of pufferfish AM2 and a paralog of mammalian AM. AM2 mRNA was
      expressed in submaxillary gland, kidney, stomach, ovary, lymphoid tissues and
      pancreas of mice, but not in adrenal and testis. Intravenous injection of
      synthetic mature AM2 decreased arterial pressure more potently than AM, and
      induced antidiuresis and antinatriuresis in mice. These results show that at
      least two peptides, AM and AM2, comprise an adrenomedullin family in mammals, and
      that AM2 may play pivotal roles in cardiovascular and body fluid regulation.

PMID- 14706826
TI  - Compact intergenic regions of the pufferfish genome facilitate isolation of gene
      promoters: characterization of Fugu 3'-phosphoadenosine 5'-phosphosulfate
      synthase 2 (fPapss2) gene promoter function in transgenic Xenopus.
AB  - The highly compact nature of the pufferfish (Fugu rubripes) genome renders it a
      useful tool not only for annotating coding regions within vertebrate genomes, but
      also for the identification of sequences important to gene regulation. Indeed,
      owing to this compaction it will be feasible in many instances to initiate
      analyses using entire intergenic regions when mapping gene promoters; a strategy
      that is very rarely feasible with the expanded genomes of other species. Stemming
      from our interest in studying promoters expressed in chondrocytes, we selected
      for study the intergenic region upstream of Fugu 3'-phosphoadenosine 5'
      phosphosulfate synthase 2, fPapss2, a gene required for the normal development of
      cartilage extracellular matrix. Functional characterization of the entire fPapss2
      5' intergenic region was carried out by monitoring expression of the enhanced
      green fluorescent protein (EGFP) gene reporter in the developing cartilage of
      transgenic Xenopus laevis. By evaluating a series of 5' intergenic region
      deletions we defined a minimal fPapss2 sequence of approximately 300 bp that was
      essential for EGFP expression in tadpole cartilage. This functional analysis of
      an entire Fugu intergenic region, combined with the efficiency of Xenopus
      transgenesis, serves as a model for the rapid characterization of evolutionarily
      conserved regulatory regions of other pufferfish genes.

PMID- 14706827
TI  - Effect of oxygen on activation state of complex I and lack of oxaloacetate
      inhibition of complex II in Langendorff perfused rat heart.
AB  - Two main entry points for electrons into the mitochondrial respiratory chain are
      NADH:ubiquinone oxidoreductase (complex I) and succinate:ubiquinone
      oxidoreductase (complex II). Metabolic regulation of these two respiratory
      complexes is not understood in detail. It has been suggested that the Krebs cycle
      metabolic intermediate oxaloacetate (OAA) inhibits complex II in vivo, whereas
      complex I undergoes a reversible active/de-active transition. In normoxic and
      anoxic hearts it has been shown that the proportion of complex I in the active
      and de-active states is different suggesting a possible mode of regulation of the
      enzyme by oxygen concentration. In the current studies rapid isolation of
      mitochondrial membranes in a state that preserves the activity of both complex I
      and complex II has been achieved using Langendorff perfused rat hearts. The
      findings indicate that the state of activation of complex I is controlled by the
      oxygen saturation in the perfusate. In addition, these studies show that complex
      II is fully active in the mitochondrion and not inhibited by OAA regardless of
      the oxygen concentration.

PMID- 14706828
TI  - Cytokines regulate the affinity of soluble CD44 for hyaluronan.
AB  - CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan, has
      been implicated in many adhesion-dependent cellular processes including tumor
      growth and metastasis. Soluble CD44 has been identified in the serum of normal
      individuals. Furthermore, tumor progression is often associated with marked
      increases in plasma levels of soluble CD44. Release of soluble CD44 by
      proteolytic cleavage (shedding) of membrane-anchored CD44 is likely to alter
      cellular responses to the environment due to modification of the cell surface and
      the potential for soluble CD44 to influence CD44-mediated hyaluronan binding to
      cell surfaces. Cellular activation is typically required to induce hyaluronan
      binding to cell surface CD44 but the affinity of endogenous soluble CD44 for
      hyaluronan remains unknown. In this study, we demonstrate that oncostatin M and
      transforming growth factor beta1 (TGF-beta1) which stimulate hyaluronan binding
      to HTB58 lung epithelial-derived tumor cells, also induce the release of soluble
      CD44. Interestingly, soluble CD44 released by oncostatin M-treated cells retained
      the ligand-binding properties of the membrane-anchored receptor. In contrast,
      soluble CD44 released from TGF-beta1-treated HTB58 cells differed in its
      hyaluronan-binding capacity from cell surface CD44 expressed on TGF-beta1
      stimulated cells. These data indicate that the mechanisms that regulate the
      generation of soluble CD44 may also govern the binding of the released receptor
      to hyaluronan and therefore determine the impact on CD44-dependent physiologic
      and pathologic processes.

PMID- 14706829
TI  - Characterization of a novel B-CLL candidate gene--DLEU7--located in the 13q14
      tumor suppressor locus.
AB  - Deletion of chromosome 13q14 is the most frequent genetic aberration in B-cell
      chronic lymphocytic leukemia (CLL), found in more than 50% of cases, indicating
      that this region contains a gene(s) involved in the development of CLL. However,
      the pathogenic gene in the critical 13q14 region has not yet been defined. Here,
      we have cloned and characterized a novel gene, DLEU7, located adjacent to the
      consensus deleted region, and overlapping the 3' end of DLEU1 tail to tail. Human
      DLEU7 encodes a putative 221 amino acid protein, with significant conservation in
      rodents. Mutational and expression analysis in primary CLL samples failed to
      demonstrate any specific mutations in DLEU7, but no DLEU7 expression could be
      detected in CLL cells. Methylation of a CpG island in the promoter region of
      DLEU7 was further analyzed as a possible mechanism for the absence of DLEU7
      expression, and the promoter was found to be methylated in the majority of the
      CLL samples investigated.

PMID- 14706830
TI  - Identification and characterization of a novel Delta6-fatty acid desaturase gene
      from Rhizopus arrhizus.
AB  - A cDNA sequence putatively encoding a Delta(6)-fatty acid desaturase was isolated
      from Rhizopus arrhizus using reverse transcription polymerase chain reaction and
      rapid amplification of cDNA ends methods. Sequence analysis indicated that this
      cDNA sequence had an open reading frame of 1377 bp encoding 458 amino acids of 52
      kDa. The deduced amino acid sequence showed high similarity to those of fungal
      Delta(6)-fatty acid desaturases which comprised the characteristics of membrane
      bound desaturases, including three conserved histidine-rich motifs and hydropathy
      profile. A cytochrome b(5)-like domain was observed at the N-terminus. To
      elucidate the function of this novel putative desaturase, the coding sequence was
      expressed heterologously in Saccharomyces cerevisiae strain INVScl. The result
      demonstrated that the coding product of the sequence exhibited Delta(6)-fatty
      acid desaturase activity by the accumulation of gamma-linolenic acid.

PMID- 14706831
TI  - Single additional methylene group in the head-group region imparts high gene
      transfer efficacy to a transfection-incompetent cationic lipid.
AB  - In combination with equimolar 1,2-dioleoyl-L-alpha-glycero-3-phosphatidyl
      ethanolamine, a novel cholesterol-based cationic lipid with beta-alanine head
      group (2) has been demonstrated to be strikingly more efficacious (10-24-fold) in
      transfecting CHO, COS-1 and HepG2 cells than its glycine analog (1) containing
      just one less methylene unit in its head-group region. Syntheses,
      characterizations and in vitro transfection biology of lipids 1 and 2 are
      described. Present findings demonstrate that even truly minor structural
      alterations, such as inclusion of just one additional methylene functionality in
      the polar head-group region, can convert an essentially transfection-incompetent
      cholesterol-based cationic amphiphile to a remarkably efficient cationic
      transfection lipid.

PMID- 14706832
TI  - In vivo interaction between CDKA and eIF4A: a possible mechanism linking
      translation and cell proliferation.
AB  - In a proteomics-based screen for proteins interacting with cyclin-dependent
      protein kinase (CDK), we have identified a novel CDK complex containing the
      eukaryotic translation initiation factor, eIF4A. Reciprocal immunoprecipitations
      using antibodies against eIF4A indicate that the interaction is specific. The
      CDKA-eIF4A complex is abundant in actively proliferating and growing cells but is
      absent from cells that have ceased dividing. The CDKA-eIF4A complex contains
      kinase activity that is sensitive to the CDK-specific inhibitor roscovitine. This
      interaction points to a possible molecular mechanism linking cell proliferation
      with translational control.

PMID- 14706833
TI  - Identification of the primary electron donor in PS II of the Chl d-dominated
      cyanobacterium Acaryochloris marina.
AB  - The primary electron donor of photosystem (PS) II in the chlorophyll (Chl) d
      dominated cyanobacterium Acaryochloris marina was confirmed by delayed
      fluorescence (DF) and further proved by pigment contents of cells grown under
      several light intensities. The DF was found only in the Chl a region, identical
      to Synechocystis sp. PCC 6803, and disappeared following heat treatment. Pigment
      analyses indicated that at least two Chl a molecules were present per each two
      pheophytin a molecules, and these Chl a molecules are assigned to P(D1) and
      P(D2). These findings clearly indicate that Chl a is required for water oxidation
      in PS II.

PMID- 14706834
TI  - AtPNP-A is a systemically mobile natriuretic peptide immunoanalogue with a role
      in Arabidopsis thaliana cell volume regulation.
AB  - Cellular and physiological evidence suggests the presence of a novel class of
      systemically mobile plant molecules that are recognized by antibodies against
      vertebrate atrial natriuretic peptides (ANPs). In order to characterize the
      function of these immunoanalogues we have expressed the full-length recombinant
      (AtPNP-A[1-126]) and demonstrate that this molecule induces osmoticum-dependent
      H(2)O uptake into protoplasts at nanomolar concentrations and thus affects cell
      volume. A similar response is also seen with a recombinant that does not contain
      the signal peptide (AtPNP-A[26-126]) as well as a short domain (AtPNP-A[33-66])
      that shows homology to the vertebrate peptide. Taken together, these findings
      suggest that AtPNP-A has an important and systemic role in plant growth and
      homeostasis.

PMID- 14706835
TI  - 8-Oxoguanine induces intramolecular DNA damage but free 8-oxoguanine protects
      intermolecular DNA from oxidative stress.
AB  - 7,8-Dihydro-8-oxoguanine (8-oxoguanine; 8-oxo-G), one of the major oxidative DNA
      adducts, is highly susceptible to further oxidation by radicals. We confirmed the
      higher reactivity of 8-oxo-G toward reactive oxygen (singlet oxygen and hydroxyl
      radical) or nitrogen (peroxynitrite) species as compared to unmodified base. In
      this study, we raised the question about the effect of this high reactivity
      toward radicals on intramolecular and intermolecular DNA damage. We found that
      the amount of intact nucleoside in oligodeoxynucleotide containing 8-oxo-G
      decreased more by various radicals at higher levels of 8-oxo-G incorporation, and
      that the oligodeoxynucleotide damage and plasmid cleavage by hydroxyl radical
      were inhibited in the presence of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG).
      We conclude that 8-oxo-G within DNA induces intramolecular DNA base damage, but
      that free 8-oxo-G protects intermolecular DNA from oxidative stress. These
      results suggest that 8-oxo-G within DNA must be rapidly released to protect DNA
      from overall oxidative damage.

PMID- 14706836
TI  - Production of endogenous matrix superoxide from mitochondrial complex I leads to
      activation of uncoupling protein 3.
AB  - Superoxide generated using exogenous xanthine oxidase indirectly activates an
      uncoupling protein (UCP)-mediated proton conductance of the mitochondrial inner
      membrane. We investigated whether endogenous mitochondrial superoxide production
      could also activate proton conductance. When respiring on succinate, rat skeletal
      muscle mitochondria produced large amounts of matrix superoxide. Addition of GDP
      to inhibit UCP3 markedly inhibited proton conductance and increased superoxide
      production. Both superoxide production and the GDP-sensitive proton conductance
      were suppressed by rotenone plus an antioxidant. Thus, endogenous superoxide can
      activate the proton conductance of UCP3, which in turn limits mitochondrial
      superoxide production. These observations provide a departure point for studies
      under more physiological conditions.

PMID- 14706837
TI  - Two engineered eglin c mutants potently and selectively inhibiting kexin or
      furin.
AB  - Eglin c with mutants L45R and D42R at the P(1) and P(4) positions has been
      reported to become a stable inhibitor toward the proprotein convertases (PC),
      furin and kexin, with a K(i) of 2.3x10(-8) and 1.3x10(-10) M, respectively. The
      mutant was further engineered at the P(2)'-P(4)' positions to create a more
      potent and selective inhibitor for each enzyme. The residue Asp at P(1)' which is
      crucial for stabilizing the conformation of eglin c remained unchanged. The eglin
      c mutants cloned into the vector pGEX-2T and expressed in Escherichia coli
      (DH5alpha) were purified to homogeneity, and their inhibitory activities toward
      the purified recombinant furin and kexin were examined. The results showed that
      (1) Leu47 at P(2)' replaced with either a positively or negatively charged
      residue resulted in a decrease in inhibitory activities to both enzymes; (2) the
      replacement of Arg with Asp at P(3)' was favorable for inhibiting furin with a
      K(i) of 7.8 x 10(-9) M, but not for inhibiting kexin; (3) the replacement of Tyr
      with Glu at P(4)' increased the inhibitory activity to kexin with a K(i) of 3 x
      10(-11) M, but was almost without any influence on furin inhibition. It was
      indicated that the inhibitory specificity of eglin c could be changed from
      inhibiting elastase to inhibiting PCs by site-directed mutation at the P
      positions, while the inhibitory selectivity to furin or kexin could be optimized
      by mutation at the P' positions.

PMID- 14706838
TI  - 2-APB inhibits volume-regulated anion channels independently from intracellular
      calcium signaling modulation.
AB  - It has previously been suggested that volume-regulated anion channels (VRACs) and
      store-operated channels (SOCs) interact with each other according to their
      expected colocalization in the plasma membrane of LNCaP cells. In order to study
      interactions between these two channels, we used 2-aminoethoxydiphenyl borate (2
      APB) as a regular SOC inhibitor. Surprisingly 2-APB reduced VRAC activity in a
      dose-dependent manner (IC(50)=122.8 microM), but not 2,2-diphenyltetrahydrofuran
      (a structural analog of 2-APB). This effect was also present in keratinocytes. We
      conclude that 2-APB is an inhibitor of the VRAC family, and is also a potent tool
      to study the SOC-VRAC interaction in LNCaP cells.

PMID- 14706839
TI  - The Vr-PLC3 gene encodes a putative plasma membrane-localized phosphoinositide
      specific phospholipase C whose expression is induced by abiotic stress in mung
      bean (Vigna radiata L.).
AB  - Phosphoinositide-specific phospholipase C (PI-PLC) catalyzes the hydrolysis of
      phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate
      and diacylglycerol, both of which act as secondary messengers in animal cells. In
      this report, we identified in Vigna radiata L. (mung bean) three distinct partial
      cDNAs (pVr-PLC1, pVr-PLC2, and pVr-PLC3), which encode forms of putative PI-PLC.
      All three Vr-PLC genes were transcriptionally active and displayed unique
      patterns of expression. The Vr-PLC1 and Vr-PLC2 transcripts were constitutively
      expressed to varying degrees in every tissue of mung bean plants examined. In
      contrast, the Vr-PLC3 mRNA level was very low under normal growth conditions and
      was rapidly induced in an abscisic acid-independent manner under environmental
      stress conditions (drought and high salinity). An isolated genomic clone, about
      8.2 kb in length, showed that Vr-PLC1 and Vr-PLC3 are in tandem array in the mung
      bean genome. The predicted primary sequence of Vr-PLC3 (M(r)=67.4 kDa) is
      reminiscent of the delta-isoform of animal enzymes which contain core sequences
      found in typical PI-PLCs, such as the catalytic domain comprising X and Y motifs,
      a lipid-binding C2 domain, and the less conserved EF-hand domain. Results of in
      vivo targeting experiment using a green fluorescent protein (GFP) showed that the
      GFP-Vr-PLC3 fusion protein was localized primarily to the plasma membrane of the
      Arabidopsis protoplast. The C2 domain was essential for Vr-PLC3 to be targeted to
      the plasma membrane. The possible biological functions of stress-responsive Vr
      PLC3 in mung bean plants are discussed.

PMID- 14706840
TI  - Fibronectin is a hypoxia-independent target of the tumor suppressor VHL.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene regulates the extracellular
      matrix by controlling fibronectin deposition. To identify novel VHL target genes,
      we subjected mRNA from VHL-deficient RCC cells (786-0-pRC) and a transfectant re
      expressing wildtype VHL (786-0-VHL) to differential expression profiling. Among
      the differentially expressed genes, we detected that fibronectin is upregulated
      in the presence of VHL, while it is not affected by hypoxia. Thus regulation of
      fibronectin deposition by VHL occurs at the transcriptional level, irrespective
      of oxygen levels.

PMID- 14706841
TI  - Propionyl-coenzyme A synthetases of Ralstonia solanacearum and Salmonella
      choleraesuis display atypical kinetics.
AB  - Propionyl-coenzyme A synthetases (PrpE) of Salmonella choleraesuis and Ralstonia
      solanacearum sharing 62% identity in amino acid sequence to each other were
      cloned, expressed in Escherichia coli and purified. Both enzymes catalyzed acetyl
      , propionyl-, butyryl- and acrylyl-coenzyme A formation with the highest
      k(cat)/K(m) values for propionate. They displayed sigmoidal homotrophic
      autoactivation kinetics for propionate but not for the other acyl substrates
      tested. Besides, substrate inhibition kinetics was observed for co-substrates,
      i.e. ATP and CoA. Based on the kinetic data reported herein, the reaction
      mechanisms of the enzyme are discussed.

PMID- 14706842
TI  - Spermine is not essential for survival of Arabidopsis.
AB  - Spermine is the final product of the polyamine biosynthetic pathway and is
      ubiquitously present in most organisms. The genome of Arabidopsis thaliana has
      two genes encoding spermine synthase: ACAULIS5 (ACL5), whose loss-of-function
      mutants show a severe defect in stem elongation, and SPMS. In order to elucidate
      the function of spermine in plants, we isolated a T-DNA insertion mutant of the
      SPMS gene. Free and conjugated spermine levels in the mutant, designated spms-1,
      were significantly decreased compared with those in the wild-type, but no obvious
      morphological phenotype was observed in spms-1 plants. We further confirmed that
      acl5-1 spms-1 double mutants contained no spermine. Surprisingly, acl5-1 spms-1
      was fully as viable as the wild-type and showed no phenotype except for the
      reduced stem growth due to acl5-1. These results indicate that spermine is not
      essential for survival of Arabidopsis, at least under normal growth conditions.

PMID- 14706843
TI  - Genomic expression pattern in Saccharomyces cerevisiae cells in response to high
      hydrostatic pressure.
AB  - Gene expression patterns in response to hydrostatic pressure were determined by
      whole genome microarray hybridization. Functional classification of the 274 genes
      affected by pressure treatment of 200 MPa for 30 min revealed a stress response
      expression profile. The majority of the >2-fold upregulated genes were involved
      in stress defense and carbohydrate metabolism while most of the repressed ones
      were in cell cycle progression and protein synthesis categories. Furthermore,
      uncharacterized genes were among the 10 highest expressed sequences and
      represented 45% of the total upregulated genes. The results of this study
      revealed a hydrostatic pressure-specific stress response pattern and suggested
      interesting information about the mechanisms involved in adaptation of cells to a
      high-pressure environment.

PMID- 14706844
TI  - Cu2+ binding triggers alphaBoPrP assembly into insoluble laminar polymers.
AB  - Cu(2+) binding is so far the best characterized property of the prion protein.
      This interaction has been mapped to the N-terminal domain of the prion protein
      where multiple His residues occur largely embedded within the repetitive PHGGGWGQ
      sequence known as octarepeats. When Cu(2+) interaction is studied using a
      solution of full-length bovine prion protein containing six octarepeats at
      protein concentrations above 25 microM, a drastic increase in solution turbidity
      is observed due to the formation of insoluble cation-protein complexes that
      appear as bidimensional polymer meshes. These bidimensional meshes consist of a
      single layer of protein molecules crosslinked by Cu(2+) cations. Polymer
      formation is a cooperative process that proceeds by nucleation of protein
      molecules with a Cu(2+) site occupancy of above 2. These results support the
      hypothesis that the N-terminal domain of prion protein is a ligand binding module
      that promotes crosslinked assembly, and suggest the existence of inter-repeat
      Cu(2+) sites.

PMID- 14706845
TI  - Structural implications for heavy metal-induced reversible assembly and
      aggregation of a protein: the case of Pyrococcus horikoshii CutA.
AB  - CutA is a small protein that appears to be involved in the mechanism of divalent
      metal cation tolerance in microorganisms. Here we report the crystal structure of
      Pyrococcus horikoshii CutA (PhoCutA), with and without Cu(2+), and its metal
      binding properties. Crystallographic analyses revealed that PhoCutA forms a
      stable trimeric structure with intertwined antiparallel beta-strands. The crystal
      structure of the Cu(2+)-PhoCutA complex shows that the Cu(2+) is located at a
      trimer-trimer interface and is recognized by the side chains of one Asp(48) from
      each trimer. In an in vitro experiment, PhoCutA bound to several heavy metals,
      most of which led to reversible aggregation of the protein; i.e. the aggregates
      could be completely solubilized by addition of ethylenediamine tetraacetic acid
      (EDTA) or dialysis against metal free buffer. Substitution of Asp(48) with Ala
      led to a decrease in the amount of aggregates, suggesting the significant
      contribution of Asp(48) to the reversible aggregation. To the best of our
      knowledge, this is the first report which provides the structural evidence for
      heavy metal-induced multimerization of a protein.

PMID- 14706846
TI  - Construction of a plasminogen activator inhibitor-1 variant without measurable
      affinity to vitronectin but otherwise normal.
AB  - Vitronectin (VN) and plasminogen activator inhibitor-1 (PAI-1) have important
      functional interactions: VN stabilises the protease inhibitory activity of PAI-1
      and PAI-1 inhibits binding of adhesion receptors to VN. Having previously mapped
      the PAI-1 binding area for VN, we have now constructed a PAI-1 variant, R103A
      M112A-Q125A, without measurable affinity to VN, but with full protease inhibitory
      activity and endocytosis receptor binding. As a tool for evaluating the
      physiological and pathophysiological functions of the PAI-1-VN interaction, our
      new variant is far superior to the previously widely used PAI-1 variant Q125K,
      which we have found possesses an only about 10-fold reduced affinity to VN.

PMID- 14706847
TI  - Delivery of antisense peptide nucleic acids (PNAs) to the cytosol by disulphide
      conjugation to a lipophilic cation.
AB  - Peptide nucleic acids (PNAs) are effective antisense reagents that bind specific
      mRNAs preventing their translation. However, PNAs cannot cross cell membranes,
      hampering delivery to cells. To overcome this problem we made PNAs membrane
      permeant by conjugation to the lipophilic triphenylphosphonium (TPP) cation
      through a disulphide bond. The TPP cation led to efficient PNA uptake into the
      cytoplasm where the disulphide bond was reduced, releasing the antisense PNA to
      block expression of its target gene. This method of directing PNAs into cells is
      a significant improvement on current procedures and will facilitate in vitro and
      pharmacological applications of PNAs.

PMID- 14706849
TI  - Efficient and cost-effective experimental determination of kinetic constants and
      data: the success of a Bayesian systematic approach to drug transport, receptor
      binding, continuous culture and cell transport kinetics.
AB  - Details about the parameters of kinetic systems are crucial for progress in both
      medical and industrial research, including drug development, clinical diagnosis
      and biotechnology applications. Such details must be collected by a series of
      kinetic experiments and investigations. The correct design of the experiment is
      essential to collecting data suitable for analysis, modelling and deriving the
      correct information. We have developed a systematic and iterative Bayesian method
      and sets of rules for the design of enzyme kinetic experiments. Our method
      selects the optimum design to collect data suitable for accurate modelling and
      analysis and minimises the error in the parameters estimated. The rules select
      features of the design such as the substrate range and the number of
      measurements. We show here that this method can be directly applied to the study
      of other important kinetic systems, including drug transport, receptor binding,
      microbial culture and cell transport kinetics. It is possible to reduce the
      errors in the estimated parameters and, most importantly, increase the efficiency
      and cost-effectiveness by reducing the necessary amount of experiments and data
      points measured.

PMID- 14706848
TI  - Gbetagamma subunits stimulate p21-activated kinase 1 (PAK1) through activation of
      PI3-kinase and Akt but act independently of Rac1/Cdc42.
AB  - The p21-activated kinase (PAK) family is homologous to the yeast sterile 20
      (Ste20) and regulates a wide variety of cellular responses, including cell
      morphology, proliferation, and survival. In this study we examined the activation
      of PAK1 by Gbetagamma subunits. Co-transfection of COS7 cells with Gbeta1gamma2
      or Gbeta1gamma5 was sufficient to induce agonist-independent activation of PAK1.
      Expression of dominant/negative Rac, Cdc42, or Ras did not inhibit this
      Gbetagamma-dependent activation. Wortmannin, which inhibits phosphoinositide 3
      kinase (PI3-kinase) activity, and expression of a dominant/negative form of Akt
      were sufficient to abrogate the activation of PAK1 that was induced by
      Gbetagamma. These results reveal that stimulation of PAK1 by Gbetagamma can occur
      via a PI3-kinase and Akt pathway that does not require Rac1 or Cdc42.

PMID- 14706850
TI  - High and low affinity receptors mediate growth effects of gastrin and gastrin-Gly
      on DLD-1 human colonic carcinoma cells.
AB  - Gastrin (G17) and N-carboxymethylgastrin (G17-Gly) have been shown to stimulate
      the growth of colon cancer cells both in vivo and in vitro. The identity of the
      receptor mediating these effects is controversial. A recent study demonstrated
      the presence of a low affinity binding site for G17 and G17-Gly on the DLD-1
      human colon cancer cell line. The goal of the current study was to further
      investigate the role of this receptor in mediating the growth-promoting effects
      of gastrin peptides. Binding of [Leu(15)]G17 and [Leu(15)]G17-Gly to DLD-1 cell
      membranes in competition with [(3)H]G17-Gly was examined. Binding of
      [(3)H]cholecystokinin-8 (CCK8) to DLD-1 cell membranes was also assessed. Whole
      cell binding experiments were carried out using [(125)I-Tyr(12),Leu(15)]G17-Gly.
      In addition, the ability of [Leu(15)]G17 and [Leu(15)]G17-Gly to stimulate cell
      growth, as determined by cell counting, was tested. [Leu(15)]G17 and [Leu(15)]G17
      Gly competed with [(3)H]G17-Gly at both a high and a low affinity site on DLD-1
      membranes. The IC(50) values for [Leu(15)]G17 were 6.0 x 10(-8) M and 6.9 x 10(
      6) M while those for [Leu(15)]G17-Gly were 3.2 x 10(-9) M and 4.9 x 10(-6) M.
      [(3)H]CCK8 did not bind to either site. [Leu(15)]G17-Gly also competed with
      [(125)I-Tyr(12),Leu(15)]G17-Gly at both a high and a low affinity site on DLD-1
      cells with similar affinities as observed with membranes. [Leu(15)]G17 and
      [Leu(15)]G17-Gly significantly stimulated the growth of DLD-1 cells in a dose
      dependent and biphasic manner. The binding profiles of the peptides tested
      suggest that these sites are different from previously identified wild-type and
      mutant CCK(1) or CCK(2) receptors.

PMID- 14706851
TI  - Lipid raft-associated catechin suppresses the FcepsilonRI expression by
      inhibiting phosphorylation of the extracellular signal-regulated kinase1/2.
AB  - The major green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG), has a
      suppressive effect on the expression of the high-affinity IgE receptor
      FcepsilonRI, which is key molecule in the IgE-mediated allergic reactions. Here
      we show that EGCG binds to the cell surface and highly associates with plasma
      membrane microdomains, lipid rafts, on the human basophilic KU812 cells. The
      disruption of these lipid rafts caused a reduction of the amount of raft
      associated EGCG and the FcepsilonRI-suppressive effect of EGCG. We also found
      that EGCG has an ability to inhibit the phosphorylation of the extracellular
      signal-regulated kinase1/2 (ERK1/2) and that the ERK1/2 specific inhibitor also
      reduced FcepsilonRI expression. Moreover, the inhibitory effect elicited by EGCG
      on ERK1/2 was prevented by disruption of rafts. Thus, these results suggest that
      the interaction between EGCG and the lipid rafts is important for EGCG's ability
      to downregulate FcepsilonRI expression, and ERK1/2 may be involved in this
      suppression signal.

PMID- 14706852
TI  - Vasodilator-stimulated phosphoprotein is a substrate for protein kinase C.
AB  - Vasodilator-stimulated phosphoprotein (VASP), an actin binding protein localized
      to areas of focal contacts, is a substrate for the cyclic adenosine
      monophosphate/cyclic guanosine monophosphate (cAMP/cGMP)-dependent protein
      kinases (PKA, PKG). In this study, we show that serum stimulation of vascular
      smooth muscle cells (SMCs) induces VASP phosphorylation on Ser157, in a mechanism
      not dependent on PKA or PKG. We tested the possibility that protein kinase C
      (PKC), a regulator of cytoskeletal function, is involved. PKC inhibition or down
      regulation prevented serum-induced phosphorylation of VASP at Ser157 in rat
      vascular SMCs. Additionally, recombinant PKCalpha directly phosphorylated Ser157
      on VASP. In summary, our data support the hypothesis that PKC phosphorylates VASP
      and mediates serum-induced VASP regulation.

PMID- 14706853
TI  - beta1,3-N-Acetylglucosaminyltransferase-7 (beta3Gn-T7) acts efficiently on
      keratan sulfate-related glycans.
AB  - beta1,3-N-Acetylglucosaminyltransferase-7 (beta3Gn-T7) has been identified as an
      anti-migration factor for a lung cancer cell line but its enzymatic activity has
      not yet been characterized. Here we show that beta3Gn-T7 efficiently acts on
      keratan sulfate-related glycans including Galbeta1-->4(SO(3)(-)-->6)GlcNAcbeta1-
      >3Galbeta1-->4(SO(3)(-)-->6)GlcNAc (L2L2), while lacto-N-tetraose and lacto-N-neo
      tetraose were poor substrates. Moreover, we found that among the other five
      beta3Gn-Ts and i antigen-producing beta3Gn-T (iGn-T), beta3Gn-T2 and iGn-T act
      well on L2L2, although these specific activities were lower than those for a
      tetraantennary N-glycan. These results indicate that beta3Gn-T7 is the one that
      most efficiently elongates L2L2 and may be involved in the biosynthesis of
      keratan sulfate.

PMID- 14706854
TI  - The role of calponin in the gene profile of metastatic cells: inhibition of
      metastatic cell motility by multiple calponin repeats.
AB  - Metastasis of diseased cells is the basic event leading to death in individuals
      with cancer. Establishment of metastasis requires that tumour cells migrate from
      the site of the primary tumour into the circulation system, escape from the
      vasculature and form secondary tumours at novel sites. These processes depend to
      a large degree on cytoskeletal remodeling. We show here that multiple copies of
      the short actin-binding module CLIK(23) from human or Caenorhabditis elegans
      calponin proteins effectively inhibit cell motility on two dimensional matrices
      and suppress soft agar colony formation of metastatic melanoma and adenocarcinoma
      cells of murine and human origin. Ectopic expression of CLIK(23) modules for 30
      days results in the formation of multinucleated cells. The repeat displays true
      modular behaviour, resulting in increased cytoskeletal effects in direct
      correlation with the increase in number of modules. Our results demonstrate that
      the role of calponin in the signature profile of metastasising cells is that of a
      mechanical stabiliser of the actin cytoskeleton, which interferes with actin
      turnover by binding at a unique interface along the actin filament.

PMID- 14706855
TI  - Costimulation of the Gi-coupled ADP receptor and the Gq-coupled TXA2 receptor is
      required for ERK2 activation in collagen-induced platelet aggregation.
AB  - The stimulation of platelets by low doses of collagen induces extracellular
      signal-regulated kinase 2 (ERK2) activation. In this report, we demonstrate that
      collagen-induced ERK2 activation depends on thromboxane A(2) (TXA(2)) formation
      and ADP release. The collagen-induced ERK2 activation was inhibited by
      indomethacin (88%) and by AR-C69931MX (70%), a specific antagonist of P2Y12, a Gi
      coupled ADP receptor. AR-C69931MX (10 microM) inhibition was overcome by
      epinephrine (1 microM), an agonist of the Gi-coupled alpha(2A)-adrenergic
      receptor, suggesting that the Gi-coupled receptor was necessary for ERK2
      activation by collagen. By contrast, MRS 2179 (10 microM), a specific antagonist
      of P2Y1, a Gq-coupled ADP receptor, did not affect collagen-induced ERK2
      activation. Little or no ERK2 activation was observed with ADP alone (10 microM).
      By contrast, U46619 (10 microM), a stable analog of TXA(2), induced ERK2
      activation in an ADP-dependent manner, via the P2Y12 receptor. These results
      suggest that the Gi-dependent signaling pathway, stimulated by ADP or
      epinephrine, was not the only pathway required for ERK2 activation by collagen.
      Costimulation of the specific G(12/13)-coupled TXA(2) receptor with a low dose of
      U46619 (10 nM) and of Gi- and Gq-coupled ADP receptor (10 microM) induced very
      low levels of ERK2 activation, similar to those observed with ADP alone,
      suggesting that G(12/13) is not involved or not sufficient to induce the
      additional pathway necessary for ERK2 activation. The Gq-coupled TXA(2) receptor
      was required for ERK2 activation by U46619 (10 microM) and low doses of collagen,
      clearly showing that a coordinated pathway through both Gq from TXA(2) and Gi
      from ADP was necessary for ERK2 activation. Finally, we demonstrate that ERK2
      activation is involved in collagen-induced aggregation and secretion.

PMID- 14706856
TI  - Melanocyte-specific expression of dopachrome tautomerase is dependent on
      synergistic gene activation by the Sox10 and Mitf transcription factors.
AB  - Sox10 regulates melanocyte development at least partly through its stimulatory
      effect on Mitf gene expression. Here, we characterize the gene for dopachrome
      tautomerase (Dct/Trp2) as the second direct Sox10 target in melanocytes, arguing
      for the existence of Sox10 functions in melanocytes that are independent of its
      epistatic relationship to Mitf. Sox10 responsiveness was mediated by multiple
      binding sites within the proximal Dct/Trp2 promoter which display varying
      affinities and bind Sox10 monomers or dimers. Mitf synergistically enhanced Sox10
      dependent activation of the Dct/Trp2 promoter. Synergy appears mechanistically
      complex and requires both direct binding of Sox10 to the promoter and the
      protein's transactivation domain.

PMID- 14706857
TI  - Alkylation of human hemoglobin A0 by the antimalarial drug artemisinin.
AB  - In vitro, the heme cofactor of human iron(II) hemoglobin was efficiently and
      quickly alkylated at meso positions by the peroxide-based antimalarial drug
      artemisinin, leading to heme-artemisinin-derived covalent adducts. This reaction
      occurred in the absence of any added protease or in the presence of an excess of
      an extra non-heme protein, or even when artemisinin was added to hemolysed human
      blood. This activation of artemisinin by the heme moiety of non-digested
      hemoglobin clearly indicates the high affinity of this drug for heme, and its
      efficient alkylating ability under very mild conditions.

PMID- 14706858
TI  - Bone marrow-derived cells contribute to lung regeneration after elastase-induced
      pulmonary emphysema.
AB  - All-trans retinoic acid (ATRA) is known to reverse the anatomic and physiologic
      signs of pulmonary emphysema. However, the origin of the progenitor cells
      involved in this lung regeneration remains unclear. Recently, it was shown that
      bone marrow could be the source of progenitor cells for several cell types. Mice
      with elastase-induced emphysema were treated with ATRA, granulocyte colony
      stimulating factor (G-CSF), or a combination of both. ATRA or G-CSF promoted lung
      regeneration and increased bone marrow-derived cell (BMC) numbers in alveoli.
      Combined treatment of both had an additive effect, which indicated that BMC
      mobilization might be important in lung regeneration.

PMID- 14706859
TI  - Copper-induced oxidative stress in Saccharomyces cerevisiae targets enzymes of
      the glycolytic pathway.
AB  - Increased cellular levels of reactive oxygen species are known to arise during
      exposure of organisms to elevated metal concentrations, but the consequences for
      cells in the context of metal toxicity are poorly characterized. Using two
      dimensional gel electrophoresis, combined with immunodetection of protein
      carbonyls, we report here that exposure of the yeast Saccharomyces cerevisiae to
      copper causes a marked increase in cellular protein carbonyl levels, indicative
      of oxidative protein damage. The response was time dependent, with total-protein
      oxidation peaking approximately 15 min after the onset of copper treatment.
      Moreover, this oxidative damage was not evenly distributed among the expressed
      proteins of the cell. Rather, in a similar manner to peroxide-induced oxidative
      stress, copper-dependent protein carbonylation appeared to target glycolytic
      pathway and related enzymes, as well as heat shock proteins. Oxidative targeting
      of these and other enzymes was isoform-specific and, in most cases, was also
      associated with a decline in the proteins' relative abundance. Our results are
      consistent with a model in which copper-induced oxidative stress disables the
      flow of carbon through the preferred glycolytic pathway, and promotes the
      production of glucose-equivalents within the pentose phosphate pathway. Such re
      routing of the metabolic flux may serve as a rapid-response mechanism to help
      cells counter the damaging effects of copper-induced oxidative stress.

PMID- 14706860
TI  - Phospholipid phase transitions in homogeneous nanometer scale bilayer discs.
AB  - Nanoscale protein supported phospholipid bilayer discs, or Nanodiscs, were
      produced for the purpose of studying the phase transition behavior of the
      incorporated lipids. Nanodiscs and vesicles were prepared with two phospholipids,
      dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylcholine, and the
      phase transition of each was analyzed using laurdan fluorescence and differential
      scanning calorimetry. Laurdan is a fluorescent probe sensitive to the increase of
      hydration in the lipid bilayer that accompanies the gel to liquid crystalline
      phase transition. The emission intensity profile can be used to derive the
      generalized polarization, a measure of the relative amount of each phase present.
      Differential scanning calorimetry was used to further quantitate the phase
      transition of the phospholipids. Both methods revealed broader transitions for
      the lipids in Nanodiscs compared to those in vesicles. Also, the transition
      midpoint was shifted 3-4 degrees C higher for both lipids when incorporated into
      Nanodiscs. These findings are explained by a loss of cooperativity in the lipids
      of Nanodiscs which is attributable to the small size of the Nanodiscs as well as
      the interaction of boundary lipids with the protein encircling the discs. The
      broad transition of the Nanodisc lipid bilayer better mimics the phase behavior
      of cellular membranes than vesicles, making Nanodiscs a 'native-like' lipid
      environment in which to study membrane associated proteins.

PMID- 14706861
TI  - Critical residues for RNA discrimination of the histone hairpin binding protein
      (HBP) investigated by the yeast three-hybrid system.
AB  - The histone hairpin binding protein (HBP, also called SLBP, which stands for stem
      loop binding protein) binds specifically to a highly conserved hairpin structure
      located in the 3' UTR of the cell-cycle-dependent histone mRNAs. HBP consists of
      a minimal central RNA binding domain (RBD) flanked by an N- and C-terminal
      domain. The yeast three-hybrid system has been used to investigate the critical
      residues of the human HBP involved in the binding of its target hairpin
      structure. By means of negative selections followed by positive selections, we
      isolated mutant HBP species. Our results indicate tight relationships between the
      RBD and the N- and C-terminal domains.

PMID- 14706862
TI  - Myofibrillar tightly bound calcium in skeletal muscle fibers: a possible role of
      this cation in titin strands aggregation.
AB  - In muscle cells, part of the calcium is tightly bound to the N1- and N2-line of
      the sarcomere but its physiological significance was unknown. In the present work
      we reported the ability of a recombinant titin fragment spanning titin domains Z9
      to I1 to tightly bind calcium ions with a K(d) of 0.049+/-0.004 nM. We further
      showed that calcium induced a spontaneous aggregation of the titin fragment and
      that the major aggregate is a tetramer. The implication of these findings on the
      organization of the six titin strands that emanate from the end of the thick
      filament within the I-band is discussed.

PMID- 14706863
TI  - Distinct in vitro interaction pattern of dopamine receptor subtypes with adaptor
      proteins involved in post-endocytotic receptor targeting.
AB  - The mechanisms underlying targeted sorting of endocytosed receptors for recycling
      to the plasma membrane or degradation in lysosomes are poorly understood. In this
      report, the C-terminal tails of the five dopamine receptors (D1-D5) were
      expressed as glutathione S-transferase (GST) fusion proteins and studied for
      their interaction with ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) and
      N-ethylmaleimide-sensitive factor (NSF), which are known to be involved in post
      endocytic recycling of receptors back to the plasma membrane, and with sorting
      nexin 1 (SNX1), known to be involved in targeting receptors to lysosomal
      degradation. EBP50 did not bind any of the dopamine receptor tails. NSF bound
      strongly to D1 and D5 and only weakly to D2, D3 and D4. However, SNX1 clearly
      distinguished between D1 and D5, as only D5 bound strongly to this protein. This
      report shows that there are distinct interaction patterns for NSF and SNX1 to the
      various dopamine receptor subtypes.

PMID- 14706864
TI  - Predominant expression of Sir2alpha, an NAD-dependent histone deacetylase, in the
      embryonic mouse heart and brain.
AB  - Sir2 is an NAD-dependent histone deacetylase that functions in longevity, gene
      silencing, heterochromatin formation, DNA repair, and suppression of DNA
      recombination in yeast. The mammalian homolog Sir2alpha (SIRT1) has been shown to
      inhibit p53-dependent apoptosis, but its physiological roles are still not known.
      We found that the level of Sir2alpha expression during embryogenesis was high.
      The highest Sir2alpha mRNA expression was detected as early as embryonic day (E)
      4.5. Although the level was down-regulated during embryogenesis, a high level of
      expression was still found in the late embryonic stage (E18.5). In embryos,
      Sir2alpha was expressed at high levels in the heart, brain, spinal cord, and
      dorsal root ganglia. The expression levels in these organs were high on E10.5
      E13.5 and low on E16.5. Quantitative reverse transcription polymerase chain
      reaction showed a 60% reduction in Sir2alpha mRNA content in the heart between
      E12.5 and E14.5. After E14.5, the expression level in the heart remained constant
      up to 27 months of age. The expression pattern of Sir2alpha protein in embryonic
      hearts was consistent with that of mRNA. These results suggest new roles of
      Sir2alpha not only in early embryogenesis but also in cardiogenesis and
      neurogenesis with a stage-specific manner.

PMID- 14706865
TI  - Behaviorally-induced ultrastructural plasticity in the hippocampal region after
      cerebral ischemia.
AB  - Behavioral training has been shown to induce synaptic plasticity in both intact
      and injured animals. Because of the possibility that the adaptive changes after
      ischemic damage may make the brain more malleable to behavioral training, we
      examined the effects of complex environment (EC) housing and exercise (EX) after
      global cerebral ischemia on synaptic structural alterations. Forty-two adult male
      Wistar rats were included in the study and assigned to either ischemia or sham
      group. Following ischemic or sham surgery, rats were randomized to either EC, EX,
      or social condition (SC, paired housing) group. CA1 was processed for electron
      microscopy and unbiased stereological techniques were used to evaluate
      plasticity. Significantly decreased neuron density was seen in anterior and
      medial CA1 in ischemic animals regardless of behavioral training. Neuron density
      in anterior CA1 was 31% less than the medial area. Synaptogenesis was influenced
      by cerebral ischemia and behavioral training in that all ischemic groups and sham
      EC animals showed greater number of synapses per neuron compared to the sham EX
      and SC groups. Analysis of synapse configuration showed that the synaptogenesis
      in ischemia EX and SC rats was formed mainly by synapses with single synaptic
      boutons, whereas in the ischemia EC and sham EC rats synaptogenesis was formed
      mainly by synapses with multiple synaptic boutons. Furthermore, housing of sham
      and ischemia rats in EC resulted in increased number of synapses with perforated
      postsynaptic density. Together, these data suggest that behavioral experience in
      EC after insult may be able to enhance synaptic plasticity.

PMID- 14706866
TI  - Glycerophosphoinositol and dexamethasone improve transendothelial electrical
      resistance in an in vitro study of the blood-brain barrier.
AB  - The blood-brain barrier (BBB) maintains the homeostasis of the brain
      microenvironment, which is crucial for neuronal activity and function. Under
      pathological conditions, the BBB may fail due to yet unknown mechanisms. BBB
      failure is accompanied by an increase in the transendothelial permeability to
      substances such as sucrose that are normally extruded. Furthermore, altered BBB
      function may also lead to development of abnormal drug extrusion mechanisms
      including expression of multiple drug resistance proteins. Therefore, it is not
      surprising that strategies have been developed to "repair" the BBB in order to
      restore normal brain homeostasis and penetration/extrusion of pharmacologically
      active (noxious) substances. To this end, steroidal hormones and synthetic
      analogues such as dexamethasone (DEX) have been used to counteract BBB failure.
      However, several side effects limit the usefulness of steroid treatment in humans
      leading to the quest for developing novel strategies for BBB repair. We here show
      that, in an in vitro model of the BBB based on a co-culture of endothelial cells
      (EC) and glia, the natural compound glycerophosphoinositol (GPI) may replicate
      the effects of DEX. Thus, GPI in concentrations ranging from 3 to 100 microM
      promoted both BBB formation and repair in a dose dependent fashion. Similar
      effects were obtained with an elevated dose of DEX (10 microM); at higher
      concentrations (100 microM), DEX was cytotoxic. We conclude that the endogenous
      anti-inflammatory agent GPI may ameliorate BBB function with efficacy comparable
      to that of steroids, but with significantly fewer side effects. Further
      experiments will confirm the efficacy of this treatment in vivo and elucidate the
      pathways that lead to BBB repair after exposure to GPI.

PMID- 14706867
TI  - The neuroactive steroid 3-alpha-ol-5-beta-pregnan-20-one hemisuccinate, a
      selective NMDA receptor antagonist improves behavioral performance following
      spinal cord ischemia.
AB  - The initial response to an ischemic event is the rapid release of excitatory
      amino acid's followed by the activation of the "ischemic cascade". It has been
      suggested that neurosteroids, which act as negative modulators of excitatory
      amino acid receptors, may improve behavioral functions and promote neuronal
      survival following ischemia. The present study evaluated the pharmacological
      effects of 3-alpha-ol-5-beta-pregnan-20-one hemisuccinate (ABHS), a neurosteroid
      that inhibits excitatory amino acid receptor function, in a rabbit reversible
      spinal cord ischemia model (RSCIM). ABHS was administered (25 mg/kg)
      intravenously (i.v.) 5 or 30 min following the start of occlusion to groups of
      rabbits exposed to ischemia induced by temporary occlusion of the infrarenal
      aorta. The group P50 represents the duration of ischemia (min) associated with a
      50% probability of resultant permanent paraplegia. Quantal analysis indicated
      that the P50 of the control group was 23.44 +/- 4.32 min. Using the RSCIM,
      neuroprotection is observed if a drug significantly prolongs the P50 compared to
      the control group. Treatment with ABHS (25 mg/kg) 5 min post-occlusion
      significantly (p < 0.05) prolonged the P50 of the group to 49.18 +/- 10.44 min,
      an increase of 110%. The effect of ABHS was not durable following a single
      injection since a significant difference between the control and ABHS-treated
      groups was not measurable at 48 h. However, if ABHS was injected 5 min following
      the start of ischemia and again 24 h after ischemia, there was a persistent
      effect of the drug at 48 h. Moreover, ABHS also increased the tolerance to
      ischemia if administered 30 min following the start of occlusion. Our results
      suggest that neuroactive steroids such as ABHS, which are selective NMDA receptor
      antagonists, may have substantial therapeutic benefit for the treatment of
      ischemic injuries including spinal cord neurodegeneration and stroke.

PMID- 14706868
TI  - Labeling and dynamic imaging of synaptic vesicle-like microvesicles in PC12 cells
      using TIRFM.
AB  - Total internal reflection fluorescence microscopy (TIRFM) was employed to study
      the trafficking and exocytosis of synaptic vesicle-like microvesicles (SLMVs) in
      PC12 cells. SLMVs were labeled with vesicular acetylcholine transporter (VAChT)
      tagged with enhanced green fluorescent protein (EGFP), which displayed punctuate
      distribution under TIRFM and confocal microscopy. Immunofluorescence analysis
      confirmed the colocalization of EGFP and VAChT. No significant difference was
      observed in the distribution or sorting of VAChT when fused either at the N- or
      the C-terminus. Thus, tagging with GFP does not appear to impair or change the
      traffic of the VAChT in PC12 cells. Under TIRFM, EGFP-labeled spots moved in a
      restrained fashion, which resembled that of secretory granules and underwent
      exocytosis upon stimulation. Together, these data indicate that EGFP-tagged VAChT
      can be used to explore SLMVs trafficking using TIRFM.

PMID- 14706869
TI  - Episodic blockade of cranial nerve VIII provokes asymmetric changes in lobule X
      of the rat.
AB  - Although debilitating syndromes like Meniere's disease are in part characterized
      by recurrent or episodic vestibular disturbance the study of episodic vestibular
      disruption has only recently been possible with the introduction of a new model
      utilizing tetrodotoxin (TTX). In the present study, serial unilateral
      transtympanic administration of TTX produced behavioral symptoms indicative of
      transient vestibular disruption and novel patterns of Fos activity in the
      brainstem and cerebellum. Following two or three serial injections of TTX and a
      final survival time of 2 h, Fos immunocytochemistry revealed a distinct pattern
      of labeling in the brainstem that differed temporally from that observed
      following a single unilateral TTX injection. Specifically there was protracted
      expression of Fos in the beta subdivision of the inferior olive (IO) on the side
      ipsilateral to TTX treatment. In the cerebellum, the hallmark of episodic
      vestibular blockade was an asymmetric pattern of Fos labeling that involved all
      three layers of the cortex. In particular, there was prominent Fos labeling of
      Purkinje cells in the contra-TTX half of lobule X. In view of the fact that Fos
      labeling is not found in Purkinje cells following a single transient event or
      following peripheral vestibular ablation, it is suggested that Fos expression in
      Purkinje cells is a unique feature of episodic vestibular disruption and may
      represent a novel plastic response by a select population of Purkinje cells to
      episodic functional deafferentation.

PMID- 14706870
TI  - Vulnerability of brain tissue to inflammatory oxidant, hypochlorous acid.
AB  - CNS inflammation is a sequela of a variety of neuropathological conditions
      resulting in extensive tissue loss. Inflammation is mediated primarily by
      phagocytic cells, but the mechanisms of CNS tissue destruction are not fully
      understood. Hypochlorous acid (HOCl) is by far the most abundant agent generated
      by phagocytic cells and may be the major mediator of inflammatory tissue damage.
      However, the effects of HOCl on nervous tissue have not been examined. In this
      study we used an in vitro model system of rat brain slices to determine
      neurotoxicity of HOCl. The slices were exposed to HOCl at pathologically relevant
      doses, and the incorporation of [3H]leucine into proteins and lipids was analyzed
      in total homogenate, and in particulate fractions obtained by density gradient
      centrifugation. The results demonstrated that a brief HOCl exposure profoundly
      suppressed protein biosynthesis in the slices. Also, lipid synthesis was
      suppressed in nonmyelin particulate fraction. However, lipid synthesis in myelin
      was significantly stimulated in HOCl-exposed slices indicating that
      oligodendrocyte response to the oxidant differs from that of other CNS cells. The
      effects of HOCl could be blocked by coadministration of antioxidants, i.e., N
      acetylcystein (NAC), uric acid (UA) and ascorbic acid (AA). The protective
      potency of the antioxidants was NAC>UA>AA. In conclusion, our study demonstrated
      that HOCl generated by phagocytic cells during inflammatory episodes has a
      potential to damage surrounding CNS tissue, and that tissue damage can be
      prevented by HOCl scavenging with clinically applicable antioxidants.

PMID- 14706872
TI  - Modulation of muscarinic facilitation of epileptiform discharges in immature rat
      neocortex.
AB  - We examined the cholinergic effects on epileptiform discharge generation in
      immature (postnatal days 10-20) rat neocortex. Evoked and spontaneous field
      potentials were recorded from the deep layers of neocortical slices during
      GABA(A) receptor blockade by bicuculline methiodide (BMI, 50 microM). The
      anticholinesterase eserine (10 microM) as well as the ACh-analog carbamylcholine
      chloride (CCh, 25 microM) decreased the amplitude and duration of evoked field
      potentials and in parallel, increased significantly the rate of occurrence of
      spontaneous discharges. These effects were reversed by the muscarinic antagonist
      atropine (2.5 microM, n = 20), but not by the nicotinic receptor antagonist
      hexamethonium (50 microM, n = 3). The M1 subtype-selective muscarinic antagonist
      pirenzepine (1 microM, n = 12) blocked spontaneous discharges in 8/12 slices,
      while muscarinic antagonists of the M2 (AFDX 116 n = 4), M3 (4-DAMP n = 4) and M4
      (gallamine n = 5, tropicamide n = 6) type, all at 1 microM, only reduced their
      frequency. CCh-induced spontaneous discharges were blocked by the combination of
      the glutamate receptor antagonists AP5 and CNQX (both at 10 microM; n = 11). Gap
      junction blockers abolished them (halothane, n = 7) or reduced their frequency by
      65% (carbenoxolone, n = 8). Inhibiting Ca2+ release from intracellular stores by
      dantrolene (100 microM, n = 5) or thapsigargin (1 microM, n = 5) also depressed
      their frequencies by 55-65%. By contrast, their rates were not altered by
      perfusion with high Ca2+ (7 mM; n = 6) medium, a manipulation suppressing
      polysynaptic connections. These findings demonstrate that activation of
      muscarinic receptors, notably of the M1 type, in immature rat neocortex
      facilitates the generation of glutamatergic epileptiform discharges. These
      discharges are strongly inhibited by gap junction blockers, and are also partly
      mediated by the, presumably muscarinic receptor-dependent, mobilization of
      intracellular calcium.

PMID- 14706871
TI  - Changes of NADPH-diaphorase reactivity in lumbar spinal cord of short-term
      streptozotocin induced diabetic rats.
AB  - Diabetes is an endocrine and metabolic disorder often associated with erectile
      dysfunction and peripheral neuropathy. Among other factors, penile erection is
      induced by activation of nitric oxide synthase (NOS). Hypothalamic
      paraventricular nuclei neurons produce NO and project to spinal cord areas
      implicated in penile reflexes. These nuclei have shown an increase of NOS in
      streptozotocin-induced diabetic rats. NOS-containing neurons are identical to the
      populations of neurons selectively stained for NADPH-diaphorase activity. Using
      this technique, we have evaluated changes of NOS in the lumbar spinal cord of
      diabetic rats with or without insulin treatment. Positive staining was found in
      motoneurons, dorsal horn neurons (layer II), neurons surrounding the ependimus
      (layer X) and neurons at the intermediolateral cell column (ILCC). Diabetic
      animals showed significant decrease in reactive area and increase of the
      histochemical reaction in motoneurons from the sexual dimorphic nuclei and in
      neurons of the ILCC. A marked decrease of the number of reactive neurons was also
      observed in layer II. Morphologic alterations were observed in neurons of layer X
      as an increase in the percentage of multipolar neurons and a decrease in the
      number and length of secondary processes. The alterations observed in these
      animals were absent in the insulin treated diabetic animals. These results show
      the plasticity of lumbar spinal cord neurons, suggesting a direct participation
      of NO synthesis in the physiopathology of the erection dysfunction in diabetes.

PMID- 14706873
TI  - Ischemia-induced alterations of AMPA-type glutamate receptor subunit. Expression
      patterns in the rat retina--an immunocytochemical study.
AB  - This study investigates whether retinal ischemia/reperfusion leads to alterations
      in the expression of AMPA-type glutamate receptor (AMPAR) subunits GluR1-4. In
      ischemia-vulnerable hippocampal neurons, a subunit-specific downregulation of
      GluR2 precedes the actual neurodegeneration. Our purpose was to study whether
      retinal ischemia induces a similar downregulation of GluR2 preceding the loss of
      ganglion and amacrine cells. A 60-min ischemic period was followed by reperfusion
      lasting between 2 h and 7 days. Changes in the expression patterns of GluR1-4
      were assessed using immunocytochemistry. In the same sections, alterations in
      cell density, thickness of retinal layers, and density of apoptotic cells were
      investigated. Two-hour post-ischemia, GluR1 immunoreactivity was nearly absent
      from the inner plexiform layer (IPL). Thereafter, labeling intensity recovered
      slowly and was close to control levels at 7 days, albeit in a thinner IPL. The
      decrease in GluR2/3 labeling intensity was most profound at 4 h. The recovery of
      GluR2/3 staining intensity was slow, and staining was still decreased at 7 days.
      GluR2 immunoreactivity was not attenuated after ischemia. GluR4 labeling showed a
      similar time course as observed for GluR1, but the decrease in immunoreactivity
      was less profound and the recovery was nearly complete. The immunostaining of
      PKCalpha, a rod bipolar cell marker, was unaffected at all reperfusion times. The
      reduction of GluR staining preceded both the typical thinning of the IPL and the
      peak of cell loss, but coincided with a significant swelling of the IPL. In
      conclusion, retinal ischemia/reperfusion leads to differential changes in the
      expression of the different AMPA-type GluR subunits, which may affect excitatory
      synaptic transmission in the inner retina. However, no evidence was found for a
      preferential loss of GluR2 immunoreactivity that could account for selective
      neurodegeneration of amacrine and ganglion cells after retinal ischemia.

PMID- 14706874
TI  - Nociceptin/orphanin FQ modulates spatial learning via ORL-1 receptors in the
      dorsal hippocampus of the rat.
AB  - The endogenous peptide nociceptin (orphanin FQ) plays a role in several important
      physiological functions in the CNS such as pain, anxiety and locomotion. It has
      previously been found that injection of 10 nmol nociceptin into the CA3 region of
      the hippocampus markedly impairs spatial learning and memory in the rat. The
      present study examined the effects of lower doses of nociceptin (3.3, 1, 0.33 and
      0.1 nmol/rat) on spatial learning. The 3.3 nmol dose impaired spatial learning
      over the 5 days of training although the effect was not as strong as with 10
      nmol. In contrast, the two lower doses, 1 and 0.33 nmol/rat, improved spatial
      learning whereas the lowest dose, 0.1 nmol/rat, had no significant effect. Both
      the impairing and facilitating effect of nociceptin could be blocked by an ORL-1
      receptor antagonist, [Phe1Psi(CH(2)-NH)Gly2]NC(1-13)NH2 (10 nmol/rat), indicating
      that both effects are ORL-1 receptor-mediated. The 3.3 nmol dose of nociceptin
      did not impair the performance in the visual platform task and did not alter swim
      speed or motor activity indicating no effects on motivation or motor performance.
      Taken together, these results show that nociceptin has a biphasic dose-effect
      curve and provide further evidence for a role of this neuropeptide in cognitive
      processes in the hippocampus.

PMID- 14706875
TI  - Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal
      responses to acute psychological stress.
AB  - The thalamic paraventricular nucleus (PVT) is activated by stress and projects to
      forebrain structures directly implicated in processing stress-related
      information. Accordingly, it seems likely the PVT plays an important role in
      modulating stress responses. We examined effects of excitotoxic PVT lesions on
      forebrain Fos expression patterns normally elicited by an acute psychological
      stressor. PVT lesions significantly increased stress-induced Fos in a key stress
      processing region, the central amygdala.

PMID- 14706876
TI  - [Video-assisted surgery of the neck: fashion or not?].

PMID- 14706877
TI  - [Sentinel lymph node procedure in uterine cancers: review of the literature].
AB  - In cancer research, regional lymph node status is a major prognostic factor and a
      decision criterion for adjuvant therapy warranting the lymphadenectomy. The
      sentinel node procedure, which has emerged to reduce morbidity of extensive
      lymphadenectomy, remains a major step in the surgical management of various
      cancers. Sentinel node procedure has become a standard technique for the
      determination of the nodal stage of the disease in patients with melanoma, vulvar
      cancer and recently in breast cancer. In cervical and endometrial cancers, the
      sentinel node biopsy is still at the stage of feasibility. In this article, we
      review the technical aspects, results and clinical implications of sentinel node
      procedure in cervical and endometrial cancers.

PMID- 14706880
TI  - [Endoscopic thyroidectomy for solitary nodules].
AB  - INTRODUCTION: The aim of this study was to assess the feasibility and safety of
      endoscopic thyroidectomy. MATERIALS AND METHODS: Between September 1998 and
      February 2000, 18 patients with a solitary thyroid nodule underwent endoscopic
      thyroidectomy in a single institution. Analgesic requirement, return to normal
      activity, and cosmetic results were compared to 18 consecutive patients who had
      conventional thyroidectomy. RESULTS: Sixteen females and two males, with a mean
      age of 43 years (17-66 years) were operated on. Indications for surgery included
      indeterminate cytology (n = 8), follicular neoplasm (n = 8), Hurthle cell
      neoplasm (n = 1), and toxic thyroid nodule (n = 1). The mean nodule diameter was
      2.7 cm (0.6-7 cm). Sixteen of 18 cases were successfully completed endoscopically
      with a mean operating time of 220 min (120-330 min). There were no major
      complication, but three patients developed mild hypercarbia and one patient had
      an incidental parathyroidectomy. When compared to conventional thyroidectomy,
      patients undergoing endoscopic thyroidectomy had a significantly superior
      cosmetic result (P < 0.005) and a quicker return to normal activity (P < 0.05),
      but there was no difference in analgesic requirement. CONCLUSION: The results of
      this study seem to confirm that endoscopic thyroidectomy is a technically
      feasible and safe procedure that leads to an improved cosmetic result and a
      quicker recovery. However, conventional thyroidectomy is still recommended when
      thyroid carcinoma is suspected.

PMID- 14706881
TI  - [Laparoscopic cholecystectomy in sickle cell disease].
AB  - STUDY AIM: Sickle cell affection is a public health problem in Africa. The aims
      of this prospective study were to evaluate the early results of laparoscopic
      cholecystectomy in sickle cell patients in Senegal. METHOD: From January 1998 to
      June 2002 all the sickle cell patients undergoing a laparoscopic cholecystectomy
      were included. Intra- and post-operative protocol (blood transfusion if Hb < 9
      g/dl, rehydration, oxygenotherapy) was standardized. RESULTS: Forty-two patients
      with sickle cell of types SS-33 and AS9 were operated upon by same surgeon. One
      case of conversion due to an effraction of biliary junction was reported. One
      homozygote patient died post-operatively because of peritonitis. Two acute
      thoracic syndromes, three vaso-occlusive crisis, and two cases of wound infection
      constituted the post-operative morbidity. No case of complication was noted in
      those who underwent pre-operative transfusion. CONCLUSION: Laparoscopic
      cholecystectomy can be carried out in sickle cell patients with biliary lithiasis
      provided that general anaesthetic rules are respected.

PMID- 14706882
TI  - [Surgery of hyperparathyroidism and of its potential recurrence in the MEN I
      setting].
AB  - Hyperparathyroidism (HPT) in the setting of multiple endocrine neoplasia type 1
      (MEN I) is almost constant and occurs often early in the course of the disease.
      Underlying pathology is almost always multiglandular because of its genetic
      origin, and therefore, in case of less than subtotal parathyroidectomy,
      recurrence rate amounts to 20-40%. Operative strategy aims to find and check all
      parathyroid glands including possible supernumerary one(s) found in 30% of
      patients and to perform a subtotal parathyroidectomy. Combined transcervical
      thymectomy is a mandatory part of the procedure. Moreover HPT triggers the
      secretion of associated gastrinomas and its cure can thus delay the timing of
      duodenopancreatic surgery. In case of recurrent HPT, preoperative work-up yields
      to image the parathyroid remnant and possible supernumerary gland(s). Reoperation
      aims to remove all parathyroid tissue. Cryopreservation can be useful in case of
      permanent long-lasting symptomatic hypoparathyroidism.

PMID- 14706884
TI  - [Should preoperative biliary drainage be performed before
      pancreatoduodenectomy?].

PMID- 14706883
TI  - [Abdominal stab wound injury with omentum evisceration].
AB  - INTRODUCTION: The abdominal stab wound with omentum evisceration, represent 4 to
      20% of abdominal injuries. It causes a problem of therapeutic indication between
      selective and mandatory laparotomy. The goal of this work is to give some answers
      to this dilemma. MATERIAL AND METHODS: A retrospective study from 1992 to 2000,
      concerning 75 patients presenting an omentum evisceration. Where there were 71
      men et four women, the mean age was 25 years old. All the abdominal injuries are
      exclusively by the stab wound. These 75 patients were divided into three groups:
      group I: 24 patients (32) were immediately operated ahead of the existence of
      severity elements; group II: 18 (24%) patients had an isolated omentum
      evisceration without any elements of severity were operated immediately; group
      III: 33 (44%) were placed under clinical, radiological and ultrasound control.
      RESULTS: We have found four cases of negative laparotomy (16,7%) in group I, and
      14 (77,8%) in group II. Five secondary laparotomies (15%) were performed in group
      III. Among the 51 patients (Group II and Group III) nine (17%) had visceral
      injuries... In all of the three groups, there was a high frequency of intestinal
      organs injuries, there was no mortality and 12% of morbidity. CONCLUSION: The
      isolated omentum evisceration is a penetrating injury of the abdominal wall but
      not synonym with visceral injuries, the interventionists authors had a high rate
      of negative laparotomy. However the selective authors in the asymptomatic
      patients under clinic examination appears logical: we believe that the
      laparoscopic diagnostic and therapeutic in doubtful cases can resolve this
      problem.

PMID- 14706885
TI  - [Emphysematous cholecystitis: a pathologic entity. A case report].
AB  - Emphysematous cholecystitis is a rare but real entity, which have to be
      recognized early in order to quickly start the best treatment. We report a case
      of acute emphysematous cholecystitis diagnosed with computed tomography. A
      successful outcome was obtained by antibiotherapy and cholecystectomy in
      emergency.

PMID- 14706886
TI  - [Tubo-ovarian actinomycosis ruptured in the sigmoid colon].
AB  - Actinomyces is an anaerobic, gram-positive bacteria saprophyte of the oral
      cavity, lungs, genital and gastro-intestinal tracts. Tubo-ovarian infection is
      rare. The authors report a case of tubo-ovarian abscess, due to actinomyces
      ruptured in the sigmoid and diagnosed in a 30-year-old woman using an intra
      uterine device for more than 5 years. After salpingo-oophorectomy and partial
      sigmoid resection, pathology confirmed the diagnosis.

PMID- 14706887
TI  - [Laparoscopic treatment of common bile duct stones].
AB  - Whether for a diagnostic evaluation or for the treatment of common bile duct
      lithiasis, the laparoscopic approach is the most efficient method compared with
      the other alternatives. The authors describe in the present article the method to
      treat laparoscopically common bile duct lithiasis.

PMID- 14706888
TI  - [Resuscitative transverse thoracotomy].
AB  - The technique of resuscitative transverse thoracotomy is for use in case of
      circulatory arrest in the trauma patient. This technique, performed after
      orotracheal intubation, is initiated by a 5th intercostal space thoracostomy in
      each mid-axillary line. If the circulatory arrest is not caused by a tension
      pneumothorax, bilateral thoracotomies in the 5th intercostal spaces with
      transverse transsection of the sternum is performed. Middle vertical incision of
      the pericardium allows the evacuation of a cardiac tamponade. This wide surgical
      access has proved simple to perform, even by non experienced operators. It allows
      digital control of a heart wound, cross-clamping of the thoracic descending aorta
      or of pulmonary hilum, rapid perfusion of warm fluids through the right auricle
      and the performance of bimanual internal cardiac massage.

PMID- 14706889
TI  - [Shortened laparotomy and the "art rules" of peripheral packing].

PMID- 14706891
TI  - [Pelvic filling and perineal reconstruction with rectus major musculocutaneous
      flap after pelvectomy].

PMID- 14706892
TI  - [Ferdinand Cabanne (1920-2003)].

PMID- 14706893
TI  - [An original mechanism of action for TIMP2, a tissue-inhibitor of matrix
      metalloproteinases].

PMID- 14706894
TI  - [Hsp90: how a chaperone becomes a pharmacological target].

PMID- 14706895
TI  - [The cost of cancer, why? why?].

PMID- 14706896
TI  - [Methodology of economic assessment: example in oncology].
AB  - The increasing costs of care make it important to identify those strategies of
      greatest value from both an effectiveness and cost perspective. Economic analysis
      is characterized by a simultaneous consideration of alternatives costs and
      outcomes, and can provide useful data for managerial decision making. In this
      paper, methods of economic evaluations in general and in cancer in particular is
      reviewed. In cancer treatment, preventive, curative or palliative strategies can
      be concerned. Economic evaluation have become increasingly important in oncology
      because of the proliferation of expensive new treatments. Furthermore,
      considering quality of life effects is particularly important in oncology, where
      many treatments obtain modest improvements in response or survival. Quality of
      life measurements are also reviewed.

PMID- 14706897
TI  - [Costs, costs and more costs: which one should we use?].
AB  - A cost is not an intrinsic feature of a product in the same way as temperature is
      for water and air. It is a calculation based on theory and convention. Costs may
      be characterised by their object (an hospital admission, a hospitalization day, a
      diagnostic related group, a treatment phase), their contents (costs directly
      attributable to the patient, controllable costs, including not only departmental
      operating costs but also costs resulting from the department's activity, full
      costs including administrative and infrastructure overhead costs), the point of
      reference from where the costs are considered (from the point of view of the
      family, the health professionals suppliers, the buyers, the health care system,
      or society) and the time when the costs were calculated. The cost framework which
      must be considered in any economic evaluation must relate to the budgetary
      concerns of the party whose involvement is sought in a health care project. There
      is no all encompassing study in this field; an evaluation performed for one type
      of contributor must only consider this party's point of view.

PMID- 14706898
TI  - [Which medico-economic approaches must be taken to evaluate the impact of costly
      molecules in oncology? The model of Herceptin in the breast metastatic cancer].
AB  - In an era where health care expenditure control is a necessity, weighing a new
      treatment's cost against its added benefits is of crucial importance. These
      medico-economic analyses may be planned for the evaluation of new molecules in
      their daily use. Different methods may be used. The medico-economic evaluation of
      a drug can be performed with the use of clinical studies or modelization
      techniques. "Clinical studies" include the following methods: randomized trials,
      so-called "experimental", non-randomized studies, and observational studies. This
      classification follows a downward evolution of both the investigator's
      intervention power and the level of proof. Finally, modelization is becoming a
      commonly used tool. Randomized trials are the "gold standard" but the other, more
      pragmatic study types, providing a lesser degree of proof can complete the
      evaluation of a new molecule. One must find the best compromise between the
      study's objectives and the study type.

PMID- 14706899
TI  - [The cost of imaging in oncology practice].
AB  - The purpose of this work was to assess the part of radiology in the total cost of
      cancer in France. Lot of public and private organisms are in charge to assess the
      total health cost and their informations are easy to obtain. But there are some
      obstacles to focus on radiological cancer cost: radiology is performed in various
      places: private outpatient care practice, private and public hospitals; for same
      examination, cost varies according on the place were it's performed; we can
      assess the imaging cost in anticancer centers, but the costs of radiological
      examinations realised for cancer indications in general hospital are not
      separated from the cost of those performed for other indications; a same patient
      can migrate between private and public radiological structures for the same
      cancer, and we are not able to know the relative cost of each part or the total
      cost. In summary, we can assess the total cost of private radiology but not the
      cancer part of this cost. For public structures, we can assess the imaging
      department cost. Nevertheless this cost is independent of the number of
      examinations performed, so the paradox is: a same exploration has a different
      cost according on the place where it's realised. So, we need to create a tool
      which will permit to obtain a medical assessment of imaging cost. The FNMR
      (Federation Nationale des medecins radiologues) try to produce such tool with the
      OPIM (Observatoire pour l'imagerie). It seems important than public radiologists
      think about it.

PMID- 14706900
TI  - [The cost of radiotherapy].
AB  - The higher human and material costs induced by the development of conformal
      radiotherapy and other innovative techniques have to be evaluated. Different
      studies reflect benefit for three-dimensional conformal radiation therapy. This
      needs appropriate economic analyses (cost/benefit, cost/utility). Conclusions
      from studies are rather in favour of new technics of radiotherapy when compared
      to standard technics and alternative therapeutic procedures and justify
      investments. The two cost accounting available in France are compared. Until now,
      medical reimbursements underestimate the costs related to treatment, slowing down
      implementation of new equipment and quality therapeutic practices. The mean
      reimbursement was 1,670 Euro always under mean real costs. To promote innovative
      treatments more rational reimbursement modalities are necessary. European
      experiences demonstrate than modern radiotherapy facilities don't induce
      expensive costs (average 3,800 Euro).

PMID- 14706901
TI  - [The cost of chemotherapy].
AB  - Health expenditures keep increasing regularly for many years and the medical cost
      of cancer as well. French Social Security estimated in 1994 that reimbursed
      health care expenditures for cancer reached 5.3 billions euros (8% of health care
      budget). Two French studies based on 1996 and 1999 diagnosis related groups data
      suggest that 15 % to 25 % of stays in public hospitals are related to cancer. In
      these studies, the budget of public health system for cancer was estimated to 6
      billions euros, among which chemotherapy accounted for 16% to 18%. French Health
      authorities data show that pharmaceutical sales for anticancer drugs, which are
      mainly delivered in the hospital sector (70%) are around 1.5 billion euros in
      2002. The price of the new drugs explains a part of the burden of cancer in
      France as in the other countries. However other factors need to be highlighted
      especially the increasing incidence of cancer, the ageing of population and the
      enlarged number of eligible patients for chemotherapy. Finally, one should note
      that current French reimbursement system for chemotherapy modifies the management
      of patients (day care versus inpatient care) and the repartition of care between
      the public and private sectors.

PMID- 14706902
TI  - [Economic assessment of Caelyx versus topotecan in advanced ovarian cancer].
AB  - Ovarian cancer is the most frequent cause of death due to gynecologic malignancy
      in both the United States and in Europe. A phase III investigation compared
      second line treatment Caelyx with topotecan in patients with advanced epithelial
      ovarian carcinoma who failed a first-line platinum-containing regimen. A total of
      474 patients were enrolled Although no significant advantage of Caelyx over
      topotecan with regards to overall survival and progression was found, there were
      fewer adverse events in the Caelyx arm and Caelyx had significantly better
      quality of life profile. We conducted a cost minimization analysis of both
      treatment arms. Costs were estimated from the viewpoint of the hospital, over the
      duration of the study period (12 weeks). The frequency of adverse events was
      derived from the trial's CRF, the treatment patterns of adverse events was
      estimated for each type of adverse event and each grade for a given type of
      adverse event. Costs included that of the drug and management of adverse events.
      Because of uncertainty on actual time spent in French hospitals, administration
      costs were not valued. Adverse events valued in the analysis were: stomatitis/
      pharyngitis, PPE, nausea/vomiting diarrhea, anemia, thrombocytopenia,
      neutropenia, sepsis, fever. Drug costs and costs of blood products were valued
      using the purchase price by the hospital, costs of tests and hospital days were
      estimated from the hospital's accounting system. The drug cost per patient was
      8,735 euros for Caelyx and 6,196 euros for topotecan, the cost of adverse events
      were 528 and 3,632 euros for Caelyx and topotecan respectively, due to the high
      rate of adverse events in patient treated with topotecan. The total costs were
      9,279 and 9,938 for Caefyx and topotecan respectively. CONCLUSION: the least
      expensive management for second line advanced ovarian cancer is Caelyx. Although
      the initial cost of the drug is higher, the reduced number of adverse events
      results in a lower total cost. Because treatment with Caelyx is also associated
      with a better of quality of life, this treatment strategy could be considered
      dominant.

PMID- 14706904
TI  - [The cost of screening for breast and cervical cancer in France].
AB  - This article presents existing data on the cost of breast cancer and cervical
      screening programmes in France. The average direct cost of breast cancer
      screening was estimated at 57.77-60.51 Euro per woman attending for screening.
      Organisational costs account for 15-24% of total costs and the efficiency of
      existing screening programmes has improved over time. There is little available
      data on the cost of cervical cancer screening in France. The decentralised model
      of screening followed for both cervical and breast cancer programmes in France is
      more costly than the centralised model adopted by most other European countries.
      The best way to improve the economic value of screening programmes is to increase
      attendance rates. Attendance is currently inadequate for both screening
      programmes in France. For cervical screening, it is more cost-effective to
      increase screening attendance than to increase the frequency of screening. As
      long as screening attendance remains low, the impact of existing screening
      programmes will be suboptimal. Thus any new allocation of resources towards
      cervical and breast cancer screening in France should be assessed with caution.

PMID- 14706903
TI  - [Refining the French system of cost assessment for oncology patients following
      chemotherapy].
AB  - The aim of this study was to check the clinical predictive variables of the
      variance of the total cost by GHM for patients undergoing chemotherapy. 10
      different hospitals registered 537 hospital stays and 1,535 day care sessions.
      The initial disease, metastases, other pathologies, participation to randomised
      trial were recorded. Each day health status, pain, stage of the protocol and the
      drugs, use of catheter, pump or chamber implant were noted. Work was measured
      separately for physicians and nurses per 24 hours using a visual analogy scale.
      Lab tests and drugs were recorded for each patient. The cost of the drugs explain
      98% of the variance of the total cost for the day care and 50% for the
      hospitalisations. For the latter, beside the cost of drugs, the length of stay,
      labor, initial disease, age, pain and associated pathology are predictive
      variables. According to this results, we conclude that the drugs for chemotherapy
      should be paid separately. No other change should be made for day care. DRG for
      hospitalized patients should take into account initial disease, age and pain.

PMID- 14706905
TI  - [The cost of cancer in France: macroeconomic and microeconomic approaches,
      evolution towards a prospective payment system].
AB  - In this article we have reviewed the cost of cancer in France, based on a
      literature review. The cost of the treatment of cancer is estimated to be 10
      thousand million euros for 75,000 lives saved annually. The increasing number of
      economic evaluations of cancer use both a macro economic approach, based on DRG
      data, and a micro economic approach, based on cost result analysis. These cost
      studies provide the elements for a decision aid in the context of social demands,
      budget constraints and the evolution towards a DRG's prospective payment system
      which characterises present organisation of health care in France.

PMID- 14706906
TI  - [The "Plan Cancer" in France: an economists' point of view].
AB  - To answer patients, caregivers and professionals needs, the "Plan Cancer" has
      been presented by the French President on the 24 March 2003. This plan's measures
      form the concrete elements of a modern health care policy against cancer. It's
      likely that a plan cancer succeeding to improve patients' survival and quality of
      life would not be associated with a decrease in health care expenses. However,
      the plan cancer should target to improve our health care system productivity,
      i.e. to ensure that the gain in years of life (and in welfare) for each Euro
      invested would increase. To reach this objective, the plan cancer should consider
      four problems that health economics may highlight. The impact of biomedical
      innovations in terms of returns; the question about the rational threshold for
      allocating resources; the influence of the heterogeneity of the medical practice;
      the role of patients' preferences. We expect that emphasising these difficulties
      would allow for health economics to be better considered in the research against
      cancer and to be clearly distinguished from opinion surveys. It's the best way
      for social surveys based on direct interview of representative samples of
      patients' and their relatives to give a useful tool for democratic reflection.

PMID- 14706907
TI  - [Assessment of cancer cost at the international level : challenges and
      methodological approaches].
AB  - Historically health care data and especially health care cost rigid were not
      collected by disease. This is due on one side to a lack of readily available
      information on the diagnosis that lend to the health care given and on the other
      side to the diversity of actors and organizations taking charge of patients. This
      results in a major difficulty of linking together incompatible and separate data.
      A few countries have tried to desegregate their global health cost data in a top
      down approach. The limits of such undertakings appeared however quickly, not the
      least because of the difficulties in allocating the expenditures by sector and
      disease. Other approaches, probably more fecund in the long run, such as the one
      used by the SEER-Medicare database in the U.S. favour the linkage of individual
      patient clinical and cost data in a bottom-up approach. However one should not
      ignore the potential bias problems raised, by the use of even large databases
      such as this one. A major advantage of clinical trials for costing purposes it
      that they include homogeneous groups of patients randomly allocated to several
      treatments for comparative purposes. They are therefore potentially better
      adapted for comparing new treatments with standard reference care.

PMID- 14706909
TI  - [Death on prescription?].

PMID- 14706908
TI  - [Medicine, ethics and money].
AB  - Since the end of the Middle Ages, physicians have been paid in different ways for
      the care they give. This payment must respect the ethical principles of equity,
      autonomy and benevolence-beneficence. Equity requires that everybody be treated
      according to his needs and not according to his means, the necessary means being
      offered by physicians or provided by society. Autonomy requires that the
      physician be independent so that no other consideration--including his own
      material interest--takes precedent over the patient's interests. Benevolence
      beneficence places the emphasis on means, in accordance with evidence-based
      medicine, results being impossible to guarantee.

PMID- 14706910
TI  - ?

PMID- 14706911
TI  - [Why are chromosome translocations recurrent in privileged sites?].

PMID- 14706912
TI  - [Hormone replacement therapy in menopause and risk of breast cancer].
AB  - Many studies have analysed the relation between hormone replacement therapy use
      and breast cancer risk. We performed a synthesis of their results based on a meta
      analysis published in 1997, on fifteen observational studies published
      afterwards, and on a recent randomised trial. The accumulated evidence shows a
      higher risk of breast cancer among HRT ever users compared to non users. The risk
      increases with treatment duration and disappears a few years after the end of the
      treatment. Furthermore, recent observational studies showed that this risk may be
      higher when progestational agents are added to estrogens than when estrogens are
      used alone. This may be important in terms of public health since combination
      therapy with estrogen and progestational agents have become the standard of care
      among women with an intact uterus and are now commonly used. The effects of the
      treatments used in France, that are not those widely studied until now, must be
      evaluated, ideally through a randomized trial.

PMID- 14706913
TI  - [Current therapeutic strategies in acute lymphoblastic leukemia in the adult].
AB  - This comprehensive overview on the most recent developments in treatments of
      adult acute lymphoblastic leukemia (ALL) discuss the controversies in the
      management of adult ALL in relation with its different phases of therapy, give an
      overview of current chemotherapy and stem cell transplantation approaches.
      Treatment strategies in adult ALL have resulted in the achievement of complete
      remission rates of about 80%, and long-term disease survival in about 30% of
      patients. However, the disease appears very heterogeneous and therapeutic
      strategies are now applied to adults according to groups of ALL with different
      prognoses. Features of poor outcome (older age, hyperleukocytosis, non-T-cell
      immunophenotype, Philadelphia chromosome-positive karyotype, longer time to
      achieve complete remission) were found in about 75% of adult ALL. This review of
      the literature summarized then data regarding prognostic factors involved in the
      determination of risk-adapted strategies. New treatment options, needed to be
      developed to further improve on the therapeutic perspectives for adult patients
      with ALL, and therapeutic schedules of main cooperative groups are also reviewed.

PMID- 14706914
TI  - [Future perspectives. From basic research to the development of new therapies
      aimed at the inhibition of the different stages of signal transduction:
      applications in breast cancer].
AB  - The mechanism implicated in the carcinogenesis are better understood and the
      transduction of signal is a potential target for new agents. In this review, we
      describe the different pathways implicated in the transduction of signal and the
      potential target for new agents in breast cancer.

PMID- 14706915
TI  - [The role of cancer registries in the surveillance, epidemiologic research and
      disease prevention].
AB  - The aim of a registry is to obtain information from all new cases in a well
      defined geographic area. They represent a source of data of great scientific
      quality. They have the double interest of describing and monitoring the cancer
      risk and to conduct research from collected data or punctual investigations. In
      the field of descriptive epidemiology, they allow to estimate national incidence,
      to predict times trends in incidence, to estimate the prevalence or to analyse
      the geographic distribution of cancers. It is important to dispose of
      representative health care practices information, really in use, those of
      specialised centres series being affected by selection bias. Population-based
      survival, as computed by cancer registries is an indicator of the effectiveness
      of health systems in cancer control. In the field of analytic epidemiology,
      information is measured at an individual level in the aim of identifying risk
      factors. For such studies a cancer registry is not indispensable but the
      constituted net correspondent make them easier in a rapid identification of new
      cases and in avoiding many bias. Population-based registries are also an
      essential tool for the evaluation of organized mass-screening programmes.

PMID- 14706916
TI  - [Standards, Options and Recommendations 2002 for the management of adult patients
      with intracranial gliomas (summary report)].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which
      started in 1993, is a collaboration between the Federation of French Cancer
      Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from
      French public universities, general hospitals and private clinics. The main
      objective is the development of clinical practice guidelines to improve the
      quality of health care and the outcome of cancer patients. OBJECTIVE: To define
      clinical practice guidelines for the management of adult patients with
      intracranial glioma in collaboration with the Association of French-speaking
      Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These
      recommendations cover diagnosis, classification, treatment and follow-up of
      patients with these tumors. METHOD: The methodology is based on a literature
      review and critical appraisal by a multidisciplinary group of experts who define
      the CPGs according to the definitions of the Standards, Options and
      Recommendations project. Once the guidelines has been defined, the document is
      submitted for review by independent reviewers. RESULTS: This article is a summary
      version of the full document presenting the clinical practice guidelines with
      algorithms. The main recommendations concern the place of the surgery,
      radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the
      specific treatment strategy of grade III and IV glioma, grade II glioma,
      gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma,
      intracranial ependymoma and brain stem glioma.

PMID- 14706917
TI  - [Frequency of genetic diseases and cancer antecedents in 493 adults with visceral
      or soft tissue sarcomas].
AB  - Little is known about epidemiology of adults soft tissue and visceral sarcomas
      (ASTS). The frequency of previous cancers and associated genetic diseases has
      been analyzed out of 493 ASTS, treated between 1997 and 2002 at Oscar Lambret
      Cancer Center. Median age is 51, sex ratio is close to 1. Liposarcomas and
      malignant fibrous histiocytofibromas are the two main types (respectively 104 and
      86 cases). Upper and lower limbs are the two main locations (respectively 176 and
      75 cases). Fifteen patients had associated genetic disease, including 12 cases of
      Recklinghausen diseases. 7 out of those 15 patients have neurosarcoma. 30
      patients have previous cancers, including 7 breast cancers, 3 lymphomas and 3
      chronic lymphocytic leukemias. Four out of those 30 patients have two different
      previous cancers. 13 patients have radiation-induced sarcomas, after an average
      10-year-period, and an average dose of 53 Gy. Undifferenciated sarcomas are the
      main histologic type (8/13), followed by angiosarcomas (2/13). Radiation-induced
      sarcomas are located in the chest wall (7/13), in pelvis (2/13) and head and neck
      (2/13). Those sarcomas are high grade (10 grade III tumours). ASTS epidemiology
      is complex with different risk factors depending on histologic type.

PMID- 14706918
TI  - [Stereotaxic irradiation of brain metastasis in elderly patients].
AB  - AIMS: Analysis of results of stereotactic irradiation for brain metastases for
      patients older than 70 years. PATIENTS AND METHODS: From January 1994 to January
      2002, 53 patients received stereotactic irradiation for a total of 105 brain
      metastases. There were 26 females and 27 males. Median age was 73 years (70-86).
      Median interval between cancer diagnosis and brain metastases was 18 months (0
      216). Metastases were diagnosed after development of related clinical symptoms in
      34 patients (64.1%). Patients were irradiated for one to 6 metastases. Twenty
      nine patients (54.7%) were treated for only one metastasis. Median metastasis
      diameter and volume were respectively 24 mm (5-74.9 mm) and 2.1 cc (0.02-71.3).
      Eighty-three metastases were supratentorial (79%), and 22 subtentorial (21%).
      Forty-five underwent only one procedure (85%) and 8 patients underwent a second
      procedure for one or several new metastases. Three patients were irradiated with
      whole brain radiotherapy (WBRT) concomitantly of radiosurgery and three patients
      received WBRT after radiosurgery for development of more than four metastases or
      for carcinomatous meningitis. RESULTS: The median follow-up was 8 months (1-33).
      Median minimum and maximum doses delivered to the metastases were respectively,
      16.42 Gy (6.5-20.5) and 20.36 Gy (13.2-41.9). The median overall survival
      duration was 9 months. Three-, 6-, 12- and 18-month overall survival rates were
      respectively, 85.6% +/- 5, 65.2% +/- 7.1, 35.5% +/- 7.8 and 26.6% +/- 8.
      According to unifactorial analysis, two prognostic factors of overall survival
      were retrieved, extra-cranial disease status and RPAa (Recursive Partitioning
      Analysis for aged patients) separated in three classes including Karnofsky index
      performance status and extra-cranial disease status, respectively p = 0.043 et p
      = 0.016. According to multifactorial analysis only RPAa was an independent
      prognostic factor of overall survival (p = 0.019, RR: 0.89, 95% confidence
      interval [0.017-0.47]). Median brain disease-free survival was 12 months. Three-,
      6-, 12- and 18-month free-brain disease survival rates were, 81.5% +/- 6.4, 68.7%
      +/- 8, 47.2% +/- 9.9 and 35.4% +/- 12.6, respectively. No prognostic factor of
      free-brain disease survival was retrieved. Crude local control rate was 97%. Only
      three metastases relapsed. Six and 12-month local control rates were 98.6% +/-
      1.4 and 88.5% +/- 7.6. Among 34 patients with initial clinical symptoms, one
      patient presented an aggravation, 9 improved up to complete response (26.5%), 13
      patients presented a partial remission (38.2%) and 5 were stabilized (14.7%). For
      6 patients, data were not available. We observed 3 radionecroses and 1 hemorrhage
      of the metastases. CONCLUSION: Radiosurgery in the elderly was efficient and well
      tolerated. Age alone should not be used to deny potentially beneficial
      radiosurgery to any patient with brain metastases.

PMID- 14706919
TI  - [Analysis of cyclophosphamide in the urine of antineoplastic drugs handlers].
AB  - The first study in which amounts of cyclophosphamide were found in the urine of
      nurses handling cytotoxic drugs using gas chromatography was published in 1984.
      We carried out a similar investigation on six pharmacy technicians involved in
      the preparation of antineoplastic agents (25,000 doses per year) but the analysis
      was performed with a more sensitive method: gas chromatography-mass spectrometry
      (LOQ = 0.1 ng/ml). Cyclophosphamide was found in two urine samples (out of 104)
      from two different workers. The rates detected were just above the limit of
      quantification. No correlation was found between the amounts of cyclophosphamide
      handled and the urinary excretion. The mean urinary levels measured in this study
      are lower than those reported by other investigators. In addition, only 1.9% of
      the collected samples are positive to cyclophosphamide. The drug was detected for
      two different technicians during two different sampling periods, suggesting that
      pollution is not repeated. No relationship could be seen between urinary
      detection of cyclophosphamide and individual or general work in the cytotoxic
      preparation unit. As supported by recent datas, transdermal resorption seems to
      be the most important way of incorporation. Further investigations are necessary
      to prove this hypothesis if we want to prevent occupational exposure of people
      handling these drugs.

PMID- 14706920
TI  - [Training of pharmacy personnel in the management of a centralized unit: the
      Oncolor network experience].
AB  - The network of cancer care units in Lorraine area (Oncolor) developed management
      training for people working in chemotherapy units, and cytotoxic drug
      preparation. The programme was framed both for staff of executives (pharmacists),
      and technicians. Firstly, comparison between practices and theoretical
      recommendations lead to the elaboration of standardized operating procedures.
      Secondly, we elaborated a specific handbook for this education programme. A
      series of four-days independent sessions were organized for pharmacists and
      technicians. Each session combined theoretical and technical teaching for
      preparing antineoplastic drugs. Participants passing a successful final
      examination received a certificate from the Oncolor's network attesting their
      capacity to manage a chemotherapy unit. Four sessions were performed, with 35
      participants. Only 31 passed at final examination. This preliminary experience
      will be enlarged to all members of the network and regularly brought up to date.

PMID- 14706921
TI  - [Advanced nonsmall cell lung cancer: importance of chemotherapy in the control of
      symptoms].
AB  - Chemotherapy in advanced non-small-cell lung cancer may be a controversy because
      it is only palliative and costly. Benefit of chemotherapy is nevertheless clear
      in survival and particularly life quality. Beside this technical criteria, two
      other factors have an impact on the therapeutic decision: symptom control and
      patient's personal expectations. The aim of the strategy is to determine an
      acceptable compromise in each situation.

PMID- 14706922
TI  - [Increasing the quality of clinical trials in oncology: an important challenge].
AB  - The scientific literature publishes many articles reporting results of clinical
      trials. The criticisms which usually follow show the importance of the trial
      methodology in all of its aspects, since the results of these trials may have a
      strategic impact on the treatment of patients in the future. A clinical trial, no
      matter how many patients are included, will not have the anticipated impact if
      there are methodological biases. An inappropriate statistical analysis can always
      be redone, missing data can sometimes be retrieved, but a protocol not correctly
      followed or an inadequate strategy are fatal errors as far as the value of the
      conclusions of the trial are concerned. It is not ethical nowadays to start a
      clinical trial on humans if the results of the trials do not permit a conclusion
      because of methodological problems or inadequate resources. Each trial should
      thus be oriented in such a way so that each step is planned with an
      irreproachable quality by avoiding as much as possible methodological biases. The
      tendency today, which consists in adapting treatments more and more on an
      individual basis, will make it more difficult to undertake large simple clinical
      trials able to answer a simple question. Trials no longer escape the necessity to
      plan one or more interim analysis, since it is no longer ethical to continue to
      include patients without even thinking of looking at the results before the
      expected end of the trial, especially for severe adverse reactions.

PMID- 14706923
TI  - [Menopause hormonal treatment and risk of breast cancer: comments on the results
      of the Million Women Study].

PMID- 14706924
TI  - Dual excitation multi- fluorescence flow cytometry for detailed analyses of
      viability and apoptotic cell transition.
AB  - The discrimination of live/dead cells as well as the detection of apoptosis is a
      frequent need in many areas of experimental biology. Cell proliferation is linked
      to apoptosis and controlled by several genes. During the cell life, specific
      events can stimulate proliferation while others may trigger the apoptotic
      pathway. Very few methods (i.e. TUNEL) are now available for studies aimed at
      correlation between apoptosis and proliferation. Therefore, there is interest in
      developing new methodological approaches that are able to correlate apoptosis to
      the cell cycle phases. Recently new approaches have been proposed to detect and
      enumerate apoptotic cells by flow cytometry. Among these, the most established
      and applied are those based on the cell membrane modifications induced in the
      early phases of the apoptotic process. The dye pair Hoechst 33342 (HO) and
      Propidium Iodide (PI), thanks to their peculiar characteristics to be
      respectively permeable and impermeable to the intact cell membrane, seems to be
      very useful. Unfortunately the spectral interaction of these dyes generates a
      consistent "energy transfer" from HO to PI. The co-presence of the dyes in a
      nucleus results in a modification in the intensity of both the emitted
      fluorescences. In order to designate the damaged cells (red fluorescence) to the
      specific cell cycle phases (blue fluorescence), we have tested different staining
      protocols aimed to minimize the interference of these dyes as much as possible.
      In cell culture models, we are able to detect serum-starved apoptotic cells as
      well as to designate their exact location in the cell cycle phases using a very
      low PI concentration. Using a Partec PAS flow cytometer equipped with HBO lamp
      and argon ion laser, a double UV/blue excitation has been performed. This
      analytical approach is able to discriminate live blue cells from the damaged
      (blue-red) ones even at 0.05 micro g/mL PI. The same instrumental setting allows
      performing other multi-colour analyses including AnnexinV-FITC as well as the
      possibility to make a correlated analysis to phenotype markers.

PMID- 14706925
TI  - Cell shape and plasma membrane alterations after static magnetic fields exposure.
AB  - The biological effects of static magnetic fields (MFs) with intensity of 6 mT
      were investigated in lymphocytes and U937 cells in the presence or absence of
      apoptosis-inducing drugs by transmission (TEM) and scanning (SEM) electron
      microscopy. Lectin cytochemistry of ConA-FITC conjugates was used to analyze
      plasma membrane structural modifications. Static MFs modified cell shape, plasma
      membrane and increased the level of intracellular [Ca++] which plays an
      antiapoptotic role in both cell types. Modifications induced by the exposure to
      static MFs were irrespective of the presence or absence of apoptotic drugs or the
      cell type. Abundant lamellar-shaped microvilli were observed upon 24 hrs of
      continuous exposure to static MFs in contrast to the normally rough surface of
      U937 cells having numerous short microvilli. Conversely, lymphocytes lost their
      round shape and became irregularly elongated; lamellar shaped microvilli were
      found when cells were simultaneously exposed to static MFs and apoptosis-inducing
      drugs. In our experiments, static MFs reduced the smoothness of the cell surface
      and partially impeded changes in distribution of cell surface glycans, both
      features being typical of apoptotic cells. Cell shape and plasma membrane
      structure modifications upon static MFs exposure were time-dependent. Lamellar
      microvilli were clearly observed before the distortion of cell shape, which was
      found at long times of exposure. MFs exposure promoted the rearrangement of F
      actin filaments which, in turn, could be responsible for the cell surface
      modifications. Here we report data that support biological effects of static MFs
      on U937 cells and human lymphocytes. However, the involvement of these
      modifications in the onset of diseases needs to be further elucidated.

PMID- 14706926
TI  - Effect of human granulocyte macrophage-colony stimulating factor on
      differentiation and apoptosis of the human osteosarcoma cell line SaOS-2.
AB  - We investigated the effects of human granulocyte macrophage-colony stimulating
      factor (GM-CSF) on the relation between differentiation and apoptosis in SaOS-2
      cells, an osteoblast-like cell line. To determine the relationship between these
      cellular processes, SaOS-2 cells were treated in vitro for 1, 7 and 14 days with
      200 ng/mL GM-CSF and compared with untreated cells. Five nM insulin-like growth
      factor (IGF-I) and 30 nM okadaic acid were used as negative and positive controls
      of apoptosis, respectively. Effects on cell differentiation were determined by
      ECM (extracellular matrix) mineralization, morphology of some typical mature
      osteoblast differentiation markers, such as osteopontin and sialoprotein II (BSP
      II), and production of bone ECM components such as collagen I. The results showed
      that treatment with GM-CSF caused cell differentiation accompanied by increased
      production of osteopontin and BSP-II, together with increased ECM deposition and
      mineralization. Flow cytometric analysis of annexin V and propidium iodide
      incorporation showed that GM-CSF up-regulated apoptotic cell death of SaOS-2
      cells after 14 days of culture in contrast to okadaic acid, which stimulated SaOS
      2 apoptosis only during the early period of culture. Endonucleolytic cleavage of
      genomic DNA, detected by "Auladdering analysis"Au, confirmed these data. The
      results suggest that GM-CSF induces osteoblastic differentiation and long-term
      apoptotic cell death of the SaOS-2 human osteosarcoma cell line, which in turn
      suggests a possible in vivo physiological role for GM-CSF on human osteoblast
      cells.

PMID- 14706927
TI  - Immunohistochemical study of macrophage migration inhibitory factor in rat liver
      fibrosis induced by thioacetamide.
AB  - Macrophage migration inhibitory factor (MIF) is a molecule known to regulate
      macrophage accumulation at sites of inflammation. To elucidate the role of MIF in
      progression of liver fibrosis, the immunohistochemical localization of MIF and
      macrophages in the liver were examined. Male Wistar rats received thioacetamide
      (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and
      histological tests, it was confirmed that liver fibrosis was induced. In
      immunohistochemical analyses, the expression of MIF protein was seen in
      hepatocytes in the areas extending out from the central veins to the portal
      tracts. In particular, at 6 weeks, immunoreactivity was detected in degenerated
      hepatocytes adjacent to the fibrotic areas but hardly observed in the fibrotic
      areas. On the other hand, a number of exudate macrophages stained by antibody ED1
      were seen in the areas from the central veins to the portal tracts at 1 week and
      in the fibrotic areas at 6 weeks. Macrophages also showed a significant increase
      in number as compared with controls. These results revealed that there was a
      close relationship between the appearance of MIF expression and ED1-positive
      exudate macrophages in degenerated hepatocytes during the progression of TA
      induced liver fibrosis.

PMID- 14706928
TI  - Identification of cells secreting a thymostimulin-like substance and examination
      of some histoenzymatic pathways in aging avian primary lymphatic organs: II.
      Bursa of Fabricius.
AB  - The Bursa of Fabricius of 15 day, 1-, 3-, and 6 month-old adult chickens (White
      Leghorn strain) were studied by histological and histochemical staining,
      histoenzymatic reactions (LDH, SDH, a-GPDH, NAD, NADPH, Ca++-dependent ATP-ase,
      pH 8.5) and by anti-thymostimulin immunoreaction. Positive reactions for
      mucopolysaccharides and enzymatic activities were located in the epithelia of the
      follicles, i.e. in follicle-associated-epithelium (FAE), inter-follicle
      epithelium (IFE) and in different epithelial compartments of cortical and
      medullary zones. Positive reaction for thymostimulin-like (TS-like) substance was
      restricted to FAE cells and weakly to the basal lamina of IFE. In 6-month-old
      chickens, the FAE cells disappeared; the phenomenon of bursal regression was
      evident, although not all the follicles were involved. In the few still normal
      follicles, the good reactivity to the enzymes tested suggests that residual
      physiological activity is still present, even if reduced.

PMID- 14706929
TI  - Expression of NGF, Trka and p75 in human cartilage.
AB  - Nerve growth factor (NGF) exerts its action through two types of receptor: high
      affinity tyrosine kinase A receptor (trkA) and low-affinity p75 receptor. NGF has
      a neurotrophic role in central and peripheral nervous system development, but
      there is also clear evidence of its involvement in the developing skeleton. The
      aim of the present immunohistochemical study was to investigate the expression
      and distribution of NGF, trkA, and p75 in normal cartilaginous tissues from adult
      subjects: articular and meniscal cartilage of the knee, cartilage from the
      epiglottis, and intervertebral disc tissue. Detection of NGF mRNA was also
      performed by in situ hybridization. Immunoreaction for NGF and the two receptors
      in articular chondrocytes, chondrocyte-like cells of meniscus and annulus
      fibrosus, and chondrocytes of the epiglottis demonstrated that they are all
      expressed in hyaline, fibrous and elastic cartilaginous tissues, suggesting that
      they could be involved in cartilage physio-pathology.

PMID- 14706931
TI  - Immunogold study on lectin binding in the porcine zona pellucida and granulosa
      cells.
AB  - An ultrastructural localization of lectin receptors on the zona pellucida (ZP) of
      porcine antral oocytes and on the granulosa cells was performed using a panel of
      horseradish peroxidase-labelled lectins in conjunction with antiperoxidase
      antibody and protein A-gold. In some cases, lectin incubation was preceded by
      sialidase digestion. WGA-, Con-A-, UEA-I-, RCA-I-, PNA- and SBA-reactive sites
      were distributed differently in the porcine ZP. Sialidase digestion increased the
      positivity obtained with RCA-I and it was necessary to promote PNA and SBA
      reactivity. These results indicated that the ZP contained N-acetylglucosamine, a
      mannose, a-fucose, b-Gal-(1-4)GlcNAc, b-Gal- (1-3)GalNAc, b-GalNAc and sialic
      acid residues. We also observed the presence of vesicles in both the ooplasm and
      granulosa cells, showing a similar lectin binding pattern to that of the ZP, thus
      suggesting that the oocyte and granulosa cells are the site of synthesis of ZP
      glucidic determinants.

PMID- 14706930
TI  - Expression of non-muscle type myosin heavy polypeptide 9 (MYH9) in mammalian
      cells.
AB  - Myosin is a functional protein associated with cellular movement, cell division,
      muscle contraction and other functions. Members of the myosin super-family are
      distinguished from the myosin heavy chains that play crucial roles in cellular
      processes. Although there are many studies of myosin heavy chains in this family,
      there are fewer on non-muscle myosin heavy chains than of muscle myosin heavy
      chains. Myosin is classified as type I (myosin I) or type II (myosin II). Myosin
      I, called unconventional myosin or mini-myosin, has one head, while myosin II,
      called conventional myosin, has two heads. We transfected myosin heavy
      polypeptide 9 (MYH9) into HeLa cells as a fusion protein with enhanced green
      fluorescent protein (EGFP) and analyzed the localization and distribution of MYH9
      in parallel with those of actin and tubulin. The results indicate that MYH9
      colocalizes with actin stress fibers. Since it has recently been shown by genetic
      analysis that autosomal dominant giant platelet syndromes are MYH9-related
      disorders, our development of transfected EGFP-MYH9 might be useful for
      predicting the associations between the function of actin polymerization, the
      MYH9 motor domain, and these disorders.

PMID- 14706932
TI  - Differential distribution of transforming growth factor-alpha
      immunohistochemistry within whole gastric mucosa in rats.
AB  - Transforming growth factor-alpha (TGF-alpha) plays an important role in both
      proliferation and differentiation of mucosal cells at the gastrointestinal level,
      including stomach, where it is constitutively produced. This study evaluated the
      immunohistochemical distribution of TGF-alpha within whole gastric mucosa in
      rats, through the examination of seriate sections. Each stomach was opened along
      the greater curvature, pinned upon a cork plate, fixed in formalin and cut in 2
      mm parallel strips which were sequentially superimposed on a glass slide.
      Sections were immunostained for TGF-alpha and pictures were taken from three
      areas: greater and lesser curvature; mucosa lying between the two curvatures. The
      sections were graded on the basis of the intensity of TGF-alpha staining, which
      was scored as follows: 0) no staining; 1) weakly positive; 2) intensely positive.
      The percent number of immunopositive cells and a mean intensity were calculated.
      Gastric mucosa showed a marked immunopositivity to TGF-alpha, mainly in parietal
      cells whose cytoplasm displayed moderate to intense staining. Positive cells (and
      the mean intensity) of total mucosa were 15.7+/-6.1% (1.13+/-0.42). However, they
      were not uniformly distributed, being 26.3+/-1.9% (1.67+/-0.24) in the mucosa
      lying between the two curvatures, 12.4+/-2.5% (1.52+/-0.22) along the lesser
      curvature and 8.3+/-2.1% (0.31+/-0.17) along the greater curvature. These results
      show that parietal cells of rat gastric mucosa exhibit immunoreactivity to TGF
      alpha. Considering the gastroprotective effects of this factor, its non
      homogeneous distribution within different areas may be of importance in
      understanding the lesion pattern of gastric damage after the administration of
      noxious agents.

PMID- 14706933
TI  - Effect of retinal ablation on the expression of calbindin D28k and GABA in the
      chick optic tectum.
AB  - The effect of retinal ablation on qualitative and quantitative changes of
      calbindin D28k and GABA expression in the contralateral optic tectum was studied
      in young chicks. Fifteen days old chicks had unilateral retinal ablation and
      after 7 or 15 days, calbindin expression was analyzed by Western blot and
      immunocytochemistry. Neuronal degeneration was followed by the amino-cupric
      silver technique. After 15 days, retinal lesions produced a significant decrease
      in calbindin immunostaining in the neuropil of layers 5-6 and in the somata of
      neurons from the layers 8 and 10 of the contralateral tectum, being this effect
      less marked at 7 days post-lesion. Double staining revealed that 50-60% of cells
      in the layers 8 and 10 were calbindin and GABA positive, 30-45% were only
      calbindin positive and 5-10% were only GABAergic neurons. Retinal ablation also
      produced a decrease in the GABA expression at either 7 or 15 days after surgery.
      At 7 days, dense silver staining was observed in the layers 5-6 from the optic
      tectum contralateral to the retinal ablation, which mainly represented neuropil
      that would come from processes of retinal ganglion cells. Tectal neuronal bodies
      were not stained with silver, although some neurons were surrounded by coarse
      granular silver deposits. In conclusion, most of calbindin molecules are present
      in neurons of the tectal GABAergic inhibitory circuitry, whose functioning
      apparently depends on the integrity of the visual input. A possible role of
      calbindin in the control of intracellular Ca2+ in neurons of this circuit when
      the visual transmission arrives to the optic tectum remains to be studied.

PMID- 14706934
TI  - Experimental Maedi Visna Virus Infection in sheep: a morphological,
      immunohistochemical and PCR study after three years of infection.
AB  - A morphological, immunohistochemical and polymerase chain reaction (PCR) study
      was performed on eight ewes experimentally infected with an Italian strain of
      Maedi-Visna Virus (MVV) in order to evaluate the lesions and the viral
      distribution after three years of infection. At the moment of euthanasia, seven
      sheep were seropositive for MVV, while one sheep in poor body conditions was
      seronegative since one year. Lungs, pulmonary lymph nodes, udder, supramammary
      lymph nodes, carpal joints, the CNS, spleen and bone marrow of the eight infected
      sheep were collected for histology, for immunohistochemical detection of the MVV
      core protein p28 and for PCR amplification of a 218 bp viral DNA sequence of the
      pol region. The most common histological findings consisted of interstitial
      lymphoproliferative pneumonia and lymphoproliferative mastitis of different
      severity, while no lesions were observed in the CNS. MVV p28 antigen was
      immunohistochemically labelled in lungs, udder, pulmonary lymph nodes, spleen and
      bone marrow but not in the CNS of all the eight infected sheep. A 218 bp sequence
      of MVV pol region was detected in lung of a seropositive and of the seroconverted
      negative sheep. The results suggest that (i) MVV causes heterogeneous lesions in
      homogeneously reared ewes, (ii) MVV p28 antigen is detectable not only in
      inflammed target organs, but also in pulmonary lymph nodes, spleen and bone
      marrow, and (iii) immunohistochemistry and PCR are useful methods for Maedi-Visna
      diagnosis in suspected cases, also when serological tests are negative.

PMID- 14706935
TI  - Signal amplification by combining two advanced immunohistochemical techniques.
AB  - The immunohistochemical techniques known as EnVision trade mark + System (EVS)
      and Mirror Image Complementary Antibody (MICA) were recently introduced into
      laboratory practice because of their high sensitivity. In this paper these
      techniques were compared and their sequences combined to obtain a new method
      possibly more sensitive than the original ones. The immunohistochemical staining
      employing the avidin-biotin complex (ABC), largely used as routine, was adopted
      as a term of comparison. Samples from the small and large intestine of pigs and
      sheep were fixed in Bouin and embedded in Paraplast. The primary antibodies
      utilized were directed against the neuronal nitric oxide synthase (nNOS),
      vasoactive intestinal polypeptide (VIP) and chromogranin A (Cr A). Targets of
      these antibodies were nerve structures of the intestinal wall, as well as
      endocrine cells scattered in the mucosa of the bowel, defined neuroendocrine
      cells or paraneurons. The EVS method appeared as slightly superior to the MICA
      method regarding sensitivity of detection. The EVS/MICA (combined) method
      resulted four/eight times more effective than the original techniques regarding
      sensitivity of detection and staining intensity, both at low and high dilutions
      of the primary antibodies. Of these latter, immunopositive structures were still
      clearly identifiable, at a dilution of 1:256,000. Such efficiency could be
      explained by the high number of revealing molecules of peroxidase contained in
      the new sequence. The application of the combined method is recommended when a
      small quantity of tissue antigens needs to be detected immunohistochemically.

PMID- 14706936
TI  - Fine structural analyses of pancreatic acinar cell nuclei from mice fed on
      genetically modified soybean.
AB  - We carried out ultrastructural morphometrical and immunocytochemical analyses on
      pancreatic acinar cell nuclei from mice fed on genetically modified (GM) soybean,
      in order to investigate possible structural and molecular modifications of
      nucleoplasmic and nucleolar constituents. We found a significant lowering of
      nucleoplasmic and nucleolar splicing factors as well as a perichromatin granule
      accumulation in GM-fed mice, suggestive of reduced post-transcriptional hnRNA
      processing and/or nuclear export. This is in accordance to already described
      zymogen synthesis and processing modifications in the same animals.

PMID- 14706937
TI  - Localization and expression of two human b-defensins (HBD-1 and HBD-2) in
      intestinal biopsies of celiac patients.

PMID- 14706938
TI  - European Journal of Histochemistry: an open forum for cell biology in plants.

PMID- 14706939
TI  - Anxiety (Angst).

PMID- 14706940
TI  - Comparison of progressive cortical gray matter loss in childhood-onset
      schizophrenia with that in childhood-onset atypical psychoses.
AB  - BACKGROUND: Recent anatomical brain magnetic resonance imaging (MRI) studies show
      a striking postpsychotic progressive loss of cortical gray matter (GM) in
      patients with childhood-onset schizophrenia (COS), which appears greater than
      that seen for adult patients. However, the diagnostic specificity and the
      relationship of these changes to drug treatment and cognitive functioning remain
      unclear. We performed a comparative prospective brain MRI study in patients with
      COS and pediatric patients with transient psychosis with behavior problems
      (psychosis not otherwise specified) provisionally considered multidimensionally
      impaired (MDI). We hypothesized that cortical GM loss would occur in patients
      with COS but not in adolescents with atypical psychoses. METHODS: Anatomical
      brain MRI was performed at baseline and follow-up in 19 patients in the MDI group
      (mean [SD] age of 13.3 [3.1] years); in 23 patients with COS matched for age,
      sex, IQ score, and drug treatment (mean [SD] age of 13.9 [2.5] years); and 38
      healthy control subjects matched for age and sex (mean [SD] age of 13.3 [3.1]
      years). The mean (SD) follow-up was 2.5 (0.8) years. Volumes of the cerebrum and
      total and regional GM were obtained by using automated analysis, and percent
      change in volume across time was calculated. One-way analyses of variance with
      post hoc Tukey Honestly Significantly Different comparisons were performed to
      examine group differences in the percent change in GM across follow-up. RESULTS:
      The COS group had significantly greater total, frontal, temporal, and parietal GM
      loss than did the MDI or healthy control groups; analysis of variance post hoc P
      values ranged from.03 to.001. The MDI and control groups did not differ
      significantly from each other. CONCLUSIONS: The cortical GM volume loss in COS
      appears diagnostically specific; it was not seen in children and adolescents with
      atypical psychosis. Because both patient groups had similar early developmental
      patterns, cognitive functioning, medications, and hospitalizations, this
      progressive loss appears to be intrinsic to COS. An ongoing neurodevelopmental
      process and/or brain response specific to the illness could account for these
      changes.

PMID- 14706941
TI  - Marital and labor market status in the long run in schizophrenia.
AB  - BACKGROUND: Singleness and unemployment increase the risk of schizophrenia.
      Schizophrenia subsequently increases the risk of singleness and unemployment.
      OBJECTIVE: To describe long-term changes in marital status and labor market
      affiliation before and after the first admission with schizophrenia. DESIGN: A
      case-control study. SETTING AND PARTICIPANTS: The sample included 5341 patients
      with a diagnosis of schizophrenia at the first admission to a psychiatric
      facility between 1970 and 1999, and 53 410 matched control subjects. A person
      admitted in 1999 was followed up in the registers from 1980 to 1997 (ie, from 19
      to 2 years before admission). Individuals admitted in 1970 could be followed up
      from 10 years until 27 years after admission. MAIN OUTCOME MEASURES: Annual
      socioeconomic indicators. RESULTS: Individuals who were later hospitalized were
      more frequently living alone, unemployed, receiving social benefits, or otherwise
      outside the labor market when compared with controls, as early as 19 years before
      their first admission. For individuals with schizophrenia, the odds ratios of
      being unmarried or not being fully employed were significantly increased even 25
      years after admission. This pattern was especially pronounced for men and for
      individuals who had more admissions. The ratios increased until admission, with a
      steeper increase in the years before admission. After admission, the odds
      declined to the level shown before admission and then stabilized. CONCLUSIONS:
      Schizophrenia hinders social achievement long before the first admission. The
      first hospital episode is followed by a period during which social status does
      not deteriorate further except for the transition into disability pension.

PMID- 14706942
TI  - Modulation of cortical-limbic pathways in major depression: treatment-specific
      effects of cognitive behavior therapy.
AB  - BACKGROUND: Functional imaging studies of major depressive disorder demonstrate
      response-specific regional changes following various modes of antidepressant
      treatment. OBJECTIVE: To examine changes associated with cognitive behavior
      therapy (CBT). METHODS: Brain changes underlying response to CBT were examined
      using resting-state fluorine-18-labeled deoxyglucose positron emission
      tomography. Seventeen unmedicated, unipolar depressed outpatients (mean +/- SD
      age, 41 +/- 9 years; mean +/- SD initial 17-item Hamilton Depression Rating Scale
      score, 20 +/- 3) were scanned before and after a 15- to 20-session course of
      outpatient CBT. Whole-brain, voxel-based methods were used to assess response
      specific CBT effects. A post hoc comparison to an independent group of 13
      paroxetine-treated responders was also performed to interpret the specificity of
      identified CBT effects. RESULTS: A full course of CBT resulted in significant
      clinical improvement in the 14 study completers (mean +/- SD posttreatment
      Hamilton Depression Rating Scale score of 6.7 +/- 4). Treatment response was
      associated with significant metabolic changes: increases in hippocampus and
      dorsal cingulate (Brodmann area [BA] 24) and decreases in dorsal (BA 9/46),
      ventral (BA 47/11), and medial (BA 9/10/11) frontal cortex. This pattern is
      distinct from that seen with paroxetine-facilitated clinical recovery where
      prefrontal increases and hippocampal and subgenual cingulate decreases were seen.
      CONCLUSIONS: Like other antidepressant treatments, CBT seems to affect clinical
      recovery by modulating the functioning of specific sites in limbic and cortical
      regions. Unique directional changes in frontal cortex, cingulate, and hippocampus
      with CBT relative to paroxetine may reflect modality-specific effects with
      implications for understanding mechanisms underlying different treatment
      strategies.

PMID- 14706943
TI  - Major depression following traumatic brain injury.
AB  - BACKGROUND: Major depression is a frequent psychiatric complication among
      patients with traumatic brain injury (TBI). To our knowledge, however, the
      clinical correlates of major depression have not been extensively studied.
      OBJECTIVE: To determine the clinical, neuropsychological, and structural
      neuroimaging correlates of major depression occurring after TBI. DESIGN:
      Prospective, case-controlled, surveillance study conducted during the first year
      after the traumatic episode occurred. Settings University hospital level I trauma
      center and a specialized rehabilitation unit. METHODS: The study group consisted
      of 91 patients with TBI. In addition, 27 patients with multiple traumas but
      without evidence of central nervous system injury constituted the control group.
      The patients' conditions were evaluated at baseline and at 3, 6, and 12 months
      after the traumatic episode. Psychiatric diagnosis was made using a structured
      clinical interview and DSM-IV criteria. Neuropsychological testing and
      quantitative magnetic resonance imaging were performed at the 3-month follow-up
      visit. RESULTS: Major depressive disorder was observed in 30 (33%) of 91 patients
      during the first year after sustaining a TBI. Major depressive disorder was
      significantly more frequent among patients with TBI than among the controls.
      Patients with TBI who had major depression were more likely to have a personal
      history of mood and anxiety disorders than patients who did not have major
      depression. Patients with major depression exhibited comorbid anxiety (76.7%) and
      aggressive behavior (56.7%). Patients with major depression had significantly
      greater impairment in executive functions than their nondepressed counterparts.
      Major depression was also associated with poorer social functioning at the 6-and
      12-month follow-up, as well as significantly reduced left prefrontal gray matter
      volumes, particularly in the ventrolateral and dorsolateral regions. CONCLUSIONS:
      Major depression is a frequent complication of TBI that hinders a patient's
      recovery. It is associated with executive dysfunction, negative affect, and
      prominent anxiety symptoms. The neuropathological changes produced by TBI may
      lead to deactivation of lateral and dorsal prefrontal cortices and increased
      activation of ventral limbic and paralimbic structures including the amygdala.

PMID- 14706944
TI  - Psychiatric illness following traumatic brain injury in an adult health
      maintenance organization population.
AB  - BACKGROUND: Psychiatric illness after traumatic brain injury (TBI) has been shown
      to be prevalent in hospitalized and tertiary care patient populations. OBJECTIVE:
      To determine the risk of psychiatric illness after TBI in an adult health
      maintenance organization population. DESIGN: Prospective cohort study. SETTING:
      Large staff-model health maintenance organization. PARTICIPANTS: Nine hundred
      thirty-nine health plan members diagnosed as having TBI in 1993 and enrolled in
      the prior year, during which no TBI was ascertained. Three health plan members
      per TBI-exposed subject were randomly selected as unexposed comparisons, matched
      for age, sex, and reference date. MAIN OUTCOME MEASURE: Psychiatric illness in
      the 3 years after the TBI reference date, determined using computerized records
      of psychiatric diagnoses according to the International Classification of
      Diseases, Ninth Revision, Clinical Modification, prescriptions, and service
      utilization. RESULTS: Prevalence of any psychiatric illness in the first year was
      49% following moderate to severe TBI, 34% following mild TBI, and 18% in the
      comparison group. Among subjects without psychiatric illness in the prior year,
      the adjusted relative risk for any psychiatric illness in the 6 months following
      moderate to severe TBI was 4.0 (95% confidence interval [CI], 2.4-6.8) and
      following mild TBI was 2.8 (95% CI, 2.1-3.7; P<.001) compared with those without
      TBI. Among subjects with prior psychiatric illness, the adjusted relative risk
      for any psychiatric illness in the 6 months following moderate to severe TBI was
      2.1 (95% CI, 1.3-3.3) and following mild TBI was 1.6 (95% CI, 1.2-2.0; P =.005).
      Prior psychiatric illness significantly modified the relationship between TBI and
      subsequent psychiatric illness (P =.04) and was a significant predictor (P<.001).
      Persons with mild TBI and prior psychiatric illness had evidence of persisting
      psychiatric illness. CONCLUSIONS: Both moderate to severe and mild TBI are
      associated with an increased risk of subsequent psychiatric illness. Whereas
      moderate to severe TBI is associated with a higher initial risk, mild TBI may be
      associated with persistent psychiatric illness.

PMID- 14706945
TI  - Hormones and menopausal status as predictors of depression in women in transition
      to menopause.
AB  - BACKGROUND: Associations between depressed mood and hormonal changes during
      transition to menopause are controversial. To our knowledge, there has been no
      prospective study of these associations in women commencing when they are
      premenopausal. OBJECTIVE: To longitudinally study the associations among
      reproductive hormones, menopausal status, and other predictors of depressed mood
      in midlife women. DESIGN: Cohort study with 6 assessment periods during a 4-year
      interval. Blood samples were collected 12 times during the follicular phase (days
      2-6). SETTING: Philadelphia County, Pennsylvania. PARTICIPANTS: A randomly
      identified, population-based, stratified sample of African American (n = 218) and
      white (n = 218) women aged 35 to 47 years with regular menstrual cycles, no
      hormonal or psychotropic medication use, and no serious physical or mental health
      problems at enrollment. MAIN OUTCOME MEASURES: Center for Epidemiologic Studies
      Depression Scale score and history of depression via the Primary Care Evaluation
      of Mental Disorders. RESULTS: There was an increased likelihood of depressive
      symptoms during transition to menopause and a decreased likelihood after
      menopause after adjustment for other predictors of depression, including history
      of depression, severe premenstrual syndrome, poor sleep, age, race, and
      employment status (P =.03). The likelihood of depressive symptoms decreased for
      individuals with a rapidly increasing follicle-stimulating hormone profile (P< or
      =.001) and also decreased with age compared with premenopausal women (P =.02).
      Participant aggregate profiles with increasing estradiol levels were
      significantly associated with depressive symptoms in bivariate analysis (P
      =.053). CONCLUSIONS: Depressive symptoms as assessed herein increased during
      transition to menopause and decreased in postmenopausal women. Hormone
      associations provided corroborating evidence that the changing hormonal milieu
      contributes to dysphoric mood during transition to menopause.

PMID- 14706946
TI  - Mood disturbances and regional cerebral metabolic abnormalities in recently
      abstinent methamphetamine abusers.
AB  - BACKGROUND: Mood disturbances in methamphetamine (MA) abusers likely influence
      drug use, but the neurobiological bases for these problems are poorly understood.
      OBJECTIVE: To assess regional brain function and its possible relationships with
      negative affect in newly abstinent MA abusers. DESIGN: Two groups were compared
      by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose
      positron emission tomography) during performance of a vigilance task. SETTING:
      Participants were recruited from the general community to a research center.
      PARTICIPANTS: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared
      with 18 control subjects (8 women). MAIN OUTCOME MEASURES: Self-reports of
      depressive symptoms and anxiety were measured, as were global and relative
      glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and
      insular cortices and the amygdala, striatum, and cerebellum. RESULTS: Abusers of
      MA provided higher self-ratings of depression and anxiety than control subjects
      and differed significantly in relative regional glucose metabolism: lower in the
      anterior cingulate and insula and higher in the lateral orbitofrontal area,
      middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA
      abusers, self-reports of depressive symptoms covaried positively with relative
      glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and
      amygdala) and ratings of state and trait anxiety covaried negatively with
      relative activity in the anterior cingulate cortex and left insula. Trait anxiety
      also covaried negatively with relative activity in the orbitofrontal cortex and
      positively with amygdala activity. CONCLUSIONS: Abusers of MA have abnormalities
      in brain regions implicated in mood disorders. Relationships between relative
      glucose metabolism in limbic and paralimbic regions and self-reports of
      depression and anxiety in MA abusers suggest that these regions are involved in
      affective dysregulation and may be an important target of intervention for MA
      dependence.

PMID- 14706947
TI  - The DSM-IV rates of child and adolescent disorders in Puerto Rico: prevalence,
      correlates, service use, and the effects of impairment.
AB  - BACKGROUND: Few prevalence studies in which DSM-IV criteria were used in children
      in representative community samples have been reported. We present prevalence
      data for the child and adolescent population of Puerto Rico and examine the
      relation of DSM-IV diagnoses to global impairment, demographic correlates, and
      service use in an island-wide representative sample. METHODS: We sampled 1886
      child-caretaker dyads in Puerto Rico by using a multistage sampling design.
      Children were aged 4 to 17 years. Response rate was 90.1%. Face-to-face
      interviews of children and their primary caretakers were performed by trained
      laypersons who administered the Diagnostic Interview Schedule for Children,
      version IV (DISC-IV) in Spanish. Global impairment was measured by using the
      Children's Global Assessment Scale scored by the interviewer of the parent.
      Reports of service use were obtained by using the Service Assessment for Children
      and Adolescents. RESULTS: Although 19.8% of the sample met DSM-IV criteria
      without considering impairment, 16.4% of the population had 1 or more of the DSM
      IV disorders when a measure of impairment specific to each diagnosis was
      considered. The overall prevalence was further reduced to 6.9% when a measure of
      global impairment was added to that definition. The most prevalent disorders were
      attention-deficit/hyperactivity disorder (8.0%) and oppositional defiant disorder
      (5.5%). Children in urban settings had higher rates than those in rural regions.
      Older age was related to higher rates of major depression and social phobia, and
      younger age was related to higher rates of attention-deficit/hyperactivity
      disorder. Both overall rates and rates of specific DSM-IV/DISC-IV disorders were
      related to service use. Children with impairment without diagnosis were more
      likely to use school services, whereas children with impairment with diagnosis
      were more likely to use the specialty mental health sector. Of those with both a
      diagnosis and global impairment, only half received services from any source.
      CONCLUSIONS: Because we used the DISC-IV to apply DSM-IV criteria, the study
      yielded prevalence rates that are generally comparable with those found in
      previous surveys. The inclusion of diagnosis-specific impairment criteria reduced
      rates slightly. When global impairment criteria were imposed, the rates were
      reduced by approximately half.

PMID- 14706948
TI  - Measurement of phosphorylated tau epitopes in the differential diagnosis of
      Alzheimer disease: a comparative cerebrospinal fluid study.
AB  - BACKGROUND: Abnormal hyperphosphorylation of the microtubule-associated protein
      tau and its incorporation into neurofibrillary tangles are major hallmarks of the
      pathogenesis of Alzheimer disease (AD). Different tau phosphoepitopes can be
      sensitively detected in cerebrospinal fluid (CSF). OBJECTIVE: To compare the
      diagnostic accuracy of CSF concentrations of tau proteins phosphorylated at 3
      pathophysiologically important epitopes (p-tau) to discriminate among patients
      with AD, nondemented control subjects, and patients with other dementias. DESIGN
      AND SETTING: Cross-sectional, bicenter, memory clinic-based studies.
      PARTICIPANTS: One hundred sixty-one patients with a clinical diagnosis of AD,
      frontotemporal dementia, dementia with Lewy bodies, or vascular dementia and 45
      nondemented controls (N = 206). MAIN OUTCOME MEASURES: Levels of tau protein
      phosphorylated at threonine 231 (p-tau231), threonine 181 (p-tau181), and serine
      199 (p-tau199). The CSF p-tau protein levels were measured using 3 different
      enzyme-linked immunosorbent assays. RESULTS: The mean CSF levels of the studied p
      tau proteins were significantly elevated in patients with AD compared with the
      other groups. Applied as single markers, p-tau231and p-tau181 reached specificity
      levels greater than 75% between AD and the combined non-AD group when sensitivity
      was set at 85% or greater. Statistical differences between the assay performances
      are presented. Particularly, discrimination between AD and dementia with Lewy
      bodies was maximized using p-tau181at a sensitivity of 94% and a specificity of
      64%, and p-tau231 maximized group separation between AD and frontotemporal
      dementia with a sensitivity of 88% and a specificity of 92%. Combinations of the
      3 markers did not add discriminative power compared with the application as
      single markers. CONCLUSIONS: The p-tau proteins in CSF come closest to fulfilling
      the criteria of a biological marker of AD. There is a tendency for p-tau proteins
      to perform differently in the discrimination of primary dementia disorders from
      AD.

PMID- 14706949
TI  - Financial considerations in laparoscopic and open appendectomy.

PMID- 14706950
TI  - Counting child health care professionals: will the United States ever have a
      coherent workforce policy for children's health care?

PMID- 14706951
TI  - How adults enhance or mess up children's play.

PMID- 14706952
TI  - Influence of Medicaid managed care enrollment on emergency department utilization
      by children.
AB  - OBJECTIVE: To explore the association between Medicaid managed care plan
      enrollment and emergency department (ED) utilization. DESIGN: Retrospective
      cohort analysis using administrative claims data. PARTICIPANTS: A total of 518
      982 nondisabled children 1 to 18 years of age who were Medicaid beneficiaries in
      calendar year 2000. MAIN OUTCOME MEASURES: Annual visit rates per 1000 member
      months and incidence rate ratios for complex and noncomplex ED visits. Medicaid
      beneficiaries were classified on the basis of months enrolled in managed care.
      Administrative claims for ED visits were classified as complex or noncomplex on
      the basis of procedure and diagnostic codes. Multivariate logistic regression
      models of the incidence rate ratios were used to compare children with varying
      degrees of enrollment in Medicaid man-aged care with a reference group consisting
      of those exclusively enrolled in Medicaid managed care. RESULTS: Overall, 22% of
      children receiving Medicaid made 1 or more ED visits in 2000; 77% of ED visits
      were for noncomplex services. Children who spent less than half of their enrolled
      months in managed care used complex ED services 37% more frequently (P<.001) and
      noncomplex services 11% more frequently (P<.001) than those exclusively enrolled
      in Medicaid managed care. CONCLUSIONS: Children with all of their Medicaid
      enrollment in managed care have the lowest ED utilization rates for complex and
      noncomplex services. These results suggest that reducing delays in managed care
      plan enrollment may be an effective strategy to reduce ED utilization for this
      population.

PMID- 14706953
TI  - Which physicians are providing health care to America's children? Trends and
      changes during the past 20 years.
AB  - BACKGROUND: Although pediatricians and family physicians are trained in the care
      of children, previous studies have revealed significant differences in the
      medical care and specialty referral patterns each provides. During the 1990s,
      several developments in the population and the health care system (eg, aging of
      the population and increases in Medicaid managed care) may have resulted in
      changes to the proportion of children seeking care from one or the other
      specialty. OBJECTIVE: To determine any changes in the proportion of office visits
      for children from birth through the age of 17 years provided by pediatricians or
      family physicians from 1980 to 2000. DESIGN: Analysis of the National Ambulatory
      Medical Care Survey data sets from 1980 to 2000. During our years of interest,
      the total number of visits sampled ranged from 2524 to 9151. Visits were analyzed
      for physician type and patient age. RESULTS: There have been marked changes in
      the proportion of office visits to general pediatricians vs family physicians
      during the 1990s. Overall, the percentage of all nonsurgical physician office
      visits for children from birth through the age of 17 years made to general
      pediatricians increased significantly, from 56.2% in 1990 to 64.2% in 2000
      (P<.001). During the same period, the percentage of all nonsurgical physician
      office visits for children from birth through the age of 17 years made to family
      physicians declined significantly, from 33.7% in 1990 to 23.9% in 2000 (P<.001).
      Visits to pediatric specialists, as a proportion of all visits, increased
      significantly, from 1.6% in 1980 to 4.5% in 2000 (P<.001). CONCLUSIONS:
      Pediatricians are providing more primary care visits for children in the United
      States, and this trend has accelerated during the past 5 years. These findings
      have implications for the cost of care, the physician workforce, and the training
      of future physicians. It is unknown if these changes have had a positive or
      negative impact on the health of our nation's children.

PMID- 14706954
TI  - Body mass index and overweight in adolescents in 13 European countries, Israel,
      and the United States.
AB  - OBJECTIVE: To compare the body mass index (BMI) (calculated as weight in
      kilograms divided by the square of height in meters) and the prevalence of BMI at
      or above the 85th centile and 95th centile (overweight) in adolescents. DESIGN:
      Cross-sectional, nationally representative school-based surveys in 1997-1998 by
      means of identical data collection methods. SETTING: Austria, Czech Republic,
      Denmark, Flemish Belgium, Finland, France, Germany, Greece, Lithuania, Ireland,
      Israel, Portugal, Slovakia, Sweden, and the United States. PARTICIPANTS: A total
      of 29 242 boys and girls, aged 13 and 15 years. MAIN OUTCOME MEASURES: The BMI,
      BMI at or above the 85th centile, and BMI at or above the 95th centile
      (overweight) from self-reported height and weight. RESULTS: The highest
      prevalence of overweight was found in the United States and the lowest in
      Lithuania. On the basis of the study reference standard, the prevalence of
      overweight (percentage) in the United States was 12.6% in 13-year-old boys, 10.8%
      in 13-year-old girls, 13.9% in 15-year-old boys, and 15.1% in 15-year-old girls,
      all significantly increased. Prevalence of overweight in Lithuania was
      significantly below the expected 5%, with 1.8% in 13-year-old boys, 2.6% in 13
      year-old girls, 0.8% in 15-year-old boys, and 2.1% in 15-year-old girls. Relative
      rankings among countries were similar for BMI at or above the 85th centile,
      although there were less dramatic differences at this level. CONCLUSIONS: The
      highest prevalences of overweight were found in the United States, Ireland,
      Greece, and Portugal.

PMID- 14706955
TI  - The costs and effects of laparoscopic appendectomy in children.
AB  - BACKGROUND: Laparoscopic procedures are performed commonly in children. In
      general, the cost containment of laparoscopic surgery in children has not been
      evaluated. OBJECTIVE: To compare the costs of laparoscopic appendectomy with
      those of open appendectomy. DESIGN: Prospective clinical trial between November
      1, 1997, and April 30, 2000. For analysis, cost of supplies, operation room use,
      and recovery in the hospital and after discharge was evaluated. Costs common to
      both groups were not determined. SETTING: Operations performed in a university
      hospital.Patients Eighty-seven children aged 4 to 15 years who underwent
      appendectomy for suspected appendicitis. Patients were randomized to laparoscopic
      or open appendectomy. Intervention Laparoscopic appendectomies performed with the
      same standard set of reusable equipment. MAIN OUTCOME MEASURES: Cost surplus of
      the laparoscopic procedure and recovery after surgery were evaluated, to
      determine the costs and effects of laparoscopic appendectomy compared with those
      of open appendectomy in children. RESULTS: Excess operating and complication
      costs per procedure were 96 euros (EUR) in laparoscopic appendectomy. The
      increased operative expenses were offset by a shorter hospital stay, resulting in
      a marginal difference of 53 EUR in itemized total costs between the 2 procedures
      (total cost, 1023 EUR in the laparoscopic appendectomy group and 970 EUR in the
      open appendectomy group). After laparoscopic appendectomy, children returned to
      school and sports earlier than those who had had an open appendectomy.
      CONCLUSION: Laparoscopic appendectomy was marginally more expensive, but it
      allowed earlier return to normal daily activities than open appendectomy.

PMID- 14706956
TI  - Outcome of isolated antenatal hydronephrosis.
AB  - OBJECTIVE: To define the clinical outcome in isolated antenatal hydronephrosis
      (ANH), defined as pelviectasis without vesicoureteral reflux or urinary tract
      obstruction. STUDY DESIGN AND PATIENTS: We analyzed prospectively gathered data
      from patients with isolated ANH. Pelviectasis, graded using the anterior
      posterior diameter reference criteria, was defined by the status of the more
      severely affected kidney. Urinary tract obstruction was ruled out by
      diethylenetriamine pentaacetic acid scan when clinically indicated. Statistical
      differences were analyzed using the McNemar and chi 2 tests. RESULTS: Isolated
      ANH was defined in 63 patients. The first postnatal ultrasonogram (mean +/- SD
      age, 18.4 +/- 17.8 days) revealed resolution of ANH in 16 (25%), mild
      pelviectasis in 34 (54%), and moderate or severe pelviectasis in 13 (21%).
      Ultrasonogram at the last follow-up visit (23.3 +/- 14.8 months) in 57 patients
      demonstrated normal pelvic diameter or mild pelviectasis in 47 (82%) (P =.002).
      In the 13 patients with moderate or severe neonatal pelviectasis, severity
      decreased in 11 (85%). Deterioration of any grade of pelviectasis occurred in
      only 3 (5%) of 57 patients. Renal growth, measured by renal length, was normal in
      all 57 patients. CONCLUSION: Isolated ANH resolves or improves in most patients
      during the first 2 years of life.

PMID- 14706957
TI  - A randomized intervention since infancy to reduce intake of saturated fat:
      calorie (energy) and nutrient intakes up to the age of 10 years in the Special
      Turku Coronary Risk Factor Intervention Project.
AB  - OBJECTIVE: To evaluate the longitudinal impact of dietary counseling on
      children's nutrient intake. DESIGN: A prospective, randomized, clinical trial.
      PARTICIPANTS: Children were recruited to the study between December 1, 1989, and
      May 30, 1992. At the age of 7 months, children were randomized to the
      intervention group (n = 540) or the control group (n = 522) and were followed up
      until the age of 10 years. Intervention Families in the intervention group have,
      since randomization, received regularly individualized counseling about how to
      modify the quality and quantity of fat in the child's diet, the goal being an
      unsaturated-saturated fat ratio of 2:1. MAIN OUTCOME MEASURES: Nutrient intakes
      between the ages of 4 and 10 years based on annual 4-day food records. RESULTS:
      The fat intake of the intervention children was constantly around 30% of the
      calorie (energy) intake, while that of the control children was 2 to 3 calorie
      percentage units higher (P<.001). The intervention children received 2 to 3
      calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage
      unit more polyunsaturated fats than the control children (P<.001 for both).
      However, neither group reached the 2:1 goal set for the unsaturated-saturated
      fatty acid ratio. The vitamin and mineral intakes of the intervention and control
      children closely resembled each other despite the marked differences in fat
      intake. CONCLUSION: Individualized, biannually given, fat intake-focused dietary
      counseling that began at the child's age of 8 months continued to influence
      favorably the diet of 4- to 10-year-old intervention children without
      disadvantageous dietary effects, but the 2:1 goal for unsaturated-saturated fat
      ratio was not reached.

PMID- 14706958
TI  - Comparison of traditional and plethysmographic methods for measuring pulsus
      paradoxus.
AB  - BACKGROUND: In the evaluation of patients with acute asthma, pulsus paradoxus
      (PP) is an objective and noninvasive indicator of the severity of airway
      obstruction. However, in children PP may be difficult or impossible to measure.
      Indwelling arterial catheters facilitate the measurement of PP, but they are
      invasive and generally reserved for critically ill patients. OBJECTIVE: To
      determine the utility of the plethysmographic waveform (PPpleth) of the pulse
      oximeter in measuring PP. METHODS: Patients from the pediatric intensive care
      unit, emergency department, and inpatient wards of a tertiary care pediatric
      hospital were eligible for the study. A total of 36 patients (mean age [SD], 11.2
      [4.7] years) were enrolled in the study. Pulsus paradoxus was measured using the
      traditional auscultatory (PPausc) method with a sphygmomanometer. Pulsus
      paradoxus was then measured using a blood pressure cuff observing for the
      disappearance and reappearance of the (PPpleth) on the pulse oximeter. Mean
      difference and 95% confidence intervals were calculated for each method. The 2
      methods were also analyzed for correlation and agreement using the Pearson
      product moment correlation and a Bland and Altman plot. RESULTS: Patients with
      status asthmaticus had higher PPausc and PPpleth readings compared with
      nonasthmatic patients. Pulsus paradoxus measured by plethysmography in patients
      with and without asthma was similar to PPausc readings (mean difference, 0.6 mm
      Hg; 95% confidence interval, -0.6 to 2.1 mm Hg). Individual PPpleth readings
      showed significant correlation and agreement with PPausc readings in patients
      both with and without asthma. CONCLUSION: Measurement of PP using the pulse
      oximeter-pulse plethysmographic waveform offers a simple and noninvasive method
      for evaluating patients with airway obstruction.

PMID- 14706959
TI  - School professionals' perceptions about the impact of chronic illness in the
      classroom.
AB  - BACKGROUND: Children with chronic health conditions spend most of their day in
      the school system. The complexity of illness management and disease sequela can
      alter their school experience. However, little is known about what educators are
      concerned about if these children are in their classroom. OBJECTIVE: To assess
      educators' perceptions of the impact of having children with different chronic
      health conditions in the classroom. METHODS: Teachers and other school
      professionals in 23 elementary schools were surveyed about the impact of having a
      child with each of 6 chronic health conditions--AIDS, asthma, congenital heart
      disease, diabetes mellitus, epilepsy, and leukemia--in the classroom. They
      responded to 13 statements about the potential academic impact on the child,
      impact on peers, personal risk or liability, and additional time or attention
      demands for the teacher. Total scores were determined for the degree of perceived
      impact for each issue and chronic health condition and the proportion of teachers
      with negative perceptions for different issues. RESULTS: The mean total scores
      (2.4 of 5) showed overall a positive perception by school professionals about
      children with chronic conditions in the classroom. Acquired immunodeficiency
      syndrome and epilepsy were perceived to have the most impact and asthma the least
      impact. The 2 educator issues (time or extra attention and personal risk or
      liability) were of the most concern to educators. Fifty-three percent were
      concerned about an emergency occurring with the child in the classroom and 27%
      were concerned about legal liability. Educator concerns of the risk of classroom
      emergencies or death were disproportionate to the clinical risk of the conditions
      especially for epilepsy and congenital heart disease. CONCLUSIONS: Overall school
      professionals have positive attitudes about children with chronic health
      conditions in the classroom, but concerns about specific diseases and issues
      exist. If parents provide most of the disease information, some of the educators'
      concerns voiced in this study may not be addressed. Health care professionals can
      help by providing educators with appropriate information about the risk and
      functional impact of childhood chronic health conditions.

PMID- 14706960
TI  - The relationship between birth weight and childhood asthma: a population-based
      cohort study.
AB  - BACKGROUND: Because obesity promotes inflammation and imposes mechanical
      constraints to the airways, a high birth weight may be a risk factor for asthma
      in childhood. However, to our knowledge, few studies have examined this potential
      relationship. OBJECTIVE: To determine the relationship between high birth weight
      and risk of emergency visits for asthma during childhood. DESIGN: Population
      based cohort study. SETTING: Alberta, Canada. PARTICIPANTS: All neonates born at
      term (> or =37 weeks) between April 1, 1985, and March 31, 1988, in Alberta (N =
      83,595). We divided the cohort into birth-weight categories: low (<2.5 kg),
      normal (2.5-4.5 kg), or high (>4.5 kg). The cohort was observed prospectively for
      10 years.Main Outcome Measure Comparison of risk of emergency visits for asthma
      over 10 years across the birth-weight categories. RESULTS: Neonates born with a
      high birth weight had a significantly increased risk of emergency visits for
      asthma during childhood compared with neonates born with a normal birth weight
      (relative risk [RR], 1.16; 95% confidence interval [CI], 1.04-1.29). The
      relationship between birth weight and emergency visits for asthma beyond a birth
      weight of 4.5 kg was linear, such that every increment of 0.10 kg in birth weight
      was associated with an additional 10% (95% CI, 2%-19%) increase in the risk of
      emergency visits for asthma. Other factors associated with an elevated risk for
      emergency asthma visits during childhood included male sex (RR, 1.26; 95% CI,
      1.22-1.30), aboriginal status (RR, 1.20; 95% CI, 1.11-1.29), and low-income
      status (RR, 1.11; 95% CI, 1.06-1.16). CONCLUSIONS: A high, but not low, birth
      weight is a risk factor for increased emergency visits during childhood. The risk
      increases linearly beyond a birth weight of 4.5 kg.

PMID- 14706961
TI  - Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold
      adapted influenza virus vaccine against the 2000-2001 influenza A(H1N1) and B
      epidemic in healthy children.
AB  - BACKGROUND: The efficacy of the intranasal, live-attenuated, trivalent cold
      adapted influenza virus vaccine (CAIV-T) against influenza A(H3N2) and B
      infections in healthy persons is established, but its effectiveness against
      natural influenza A(H1N1) infection is unknown. OBJECTIVE: To assess the
      effectiveness of CAIV-T in healthy children during the 2000-2001 influenza
      A(H1N1) and B epidemic. DESIGN: Community-based, nonrandomized, open-label trial
      from August 1998 through April 2001. SETTING: Intervention and comparison
      communities in central Texas. PARTICIPANTS: Healthy children, aged 1.5 to 18
      years, from the intervention communities received a single dose of CAIV-T at
      least 1 time or more in 1998, 1999, and/or 2000. MAIN OUTCOME MEASURES: The
      incidence of medically attended acute respiratory illnesses during the 2000-2001
      influenza epidemic was compared in 3794 health plan CAIV-T recipients with age
      eligible, health plan nonrecipients in the intervention communities for direct
      effectiveness (n = 9325), and with those in the 2 comparison communities for
      total effectiveness (n = 16,264). RESULTS: The 2281 CAIV-T recipients in 2000 had
      significant direct protection against medically attended acute respiratory
      illness of 18% to 20% during the biphasic influenza A(H1N1) and B epidemic, and
      17% to 26% during influenza A(H1N1) predominance. The 931 recipients of CAIV-T in
      1999 containing influenza A/Beijing/262/95(H1N1) and B/Beijing/184/93-like
      viruses had persistent heterovariant protection against the 2000-2001 influenza
      A/New Caledonia/20/99(H1N1) and B/Sichuan/379/99 variants. The 616 recipients of
      a single CAIV-T dose in 1999 only, including those younger than 5 years with no
      prior natural exposure to influenza A(H1N1) viruses, showed persistent
      protection. CONCLUSION: Healthy children who received CAIV-T in 2000 or 1999 were
      protected against new variants of influenza A(H1N1) and B in the 2000-2001
      influenza epidemic.

PMID- 14706962
TI  - Urban children's perceptions of violence.
AB  - OBJECTIVE: To determine how preadolescent urban children conceptualize and
      experience violence in their lives. DESIGN: This qualitative study reports the
      results of focus groups designed to examine perceptions of violence among
      preadolescent urban children. Program directors were trained to conduct the
      sessions using a semistructured script. All groups were audiotaped or videotaped.
      The summaries were analyzed for recurring themes. SETTING: A community-based
      visual arts program for children designed to be a secondary violence-prevention
      program. PARTICIPANTS: There were 12 focus groups of volunteer participants. Each
      consisted of 3 to 6 children aged 8 to 12 years, separated by sex and age. Fifty
      children participated: 27 boys and 23 girls. RESULTS: These children defined
      violence in a broader way than most adults would. Not only did the children
      identify shootings and stabbings as examples of violence, but they also
      considered violence to be any act that might hurt someone's feelings (such as
      cheating and lying) or any act accompanying violence (such as cursing and
      yelling). The boys and girls were very similar in their views except regarding
      the issue of intimate-partner violence. The girls were almost universally
      concerned about this issue, but the boys seemed noticeably unaware that intimate
      partner violence was considered a form of violence. Most children felt safe at
      home, and almost no child felt safe at school. They looked to trusted adults to
      keep them safe. CONCLUSIONS: Future investigators measuring the effect of
      violence-prevention activities on preteen children should be aware that their
      definition of violence may differ from that of young children and should be
      cognizant of potential sex differences, especially around the topic of intimate
      partner violence. Those designing violence-prevention programs for children
      should consider engaging adult family members as well because children usually
      turn to them for safety.

PMID- 14706963
TI  - The effect of prior interactions with a primary care provider on nonurgent
      pediatric emergency department use.
AB  - OBJECTIVE: To determine the effect of parental reported difficulty getting care
      without long waits from a primary care provider (PCP) on nonurgent pediatric
      emergency department (ED) use. DESIGN: Case-control study. SETTING: Pediatric ED
      within an urban pediatric hospital. PARTICIPANTS: Children, aged 6 months to 12
      years, who presented with a chief complaint from a predetermined list of
      nonurgent (cases) or emergent complaints (controls). MAIN OUTCOME MEASURES:
      Caregivers assessed interactions with a PCP during the previous 12 months by
      completion of a Consumer Assessment of Health Plans (CAHPS) survey. Baseline
      demographic variables were compared. Composite CAHPS scores assessing difficulty
      meeting medical needs, including getting care without long waits, were compared
      using median tests. Multivariate logistic regression was used to assess the
      effect of getting care without long waits on nonurgent ED use. RESULTS: Of 821
      caregivers approached, 719 (87.6%) completed the survey, including 366 cases
      (50.9%) and 353 controls (49.1%). Those with emergent complaints were older,
      healthier, and more likely to be male; had higher caregiver education and income
      levels; and were more likely to have a PCP. Analysis of the CAHPS composite
      scores revealed increased difficulty meeting medical needs for those with
      nonurgent complaints, with the greatest difference noted for getting care without
      long waits (median score, 3.25 vs 3.67; P<.001). In multivariate regression,
      increased ability to get care without long waits was associated with decreased
      odds of nonurgent ED use (odds ratio, 0.48; 95% confidence interval, 0.32-0.72).
      CONCLUSION: Parental-reported previous difficulty getting care without long waits
      from a PCP is a risk factor for nonurgent ED use.

PMID- 14706964
TI  - Smoking cessation counseling with young patients: the practices of family
      physicians and pediatricians.
AB  - OBJECTIVE: To investigate family physicians' and pediatricians' practice of and
      perceived barriers to smoking cessation counseling among patients 18 years and
      younger. DESIGN: Cross-sectional mail survey conducted between November 1, 1997,
      and January 31, 1998. PARTICIPANTS: A stratified random sample selected from the
      1997 American Medical Association Physician Masterfile of 1000 family physicians
      and pediatricians who practice in urban California, work at least 10% of the time
      in ambulatory care, and have at least 10% of patients 18 years and younger. MAIN
      OUTCOME MEASURES: Physicians' adherence to 5 components of the National Cancer
      Institute's smoking cessation counseling recommendations (anticipate, ask,
      advise, assist, and arrange) and their perceived barriers to smoking cessation
      counseling. RESULTS: A total of 429 physicians participated in the study.
      Physicians of both specialties were more likely to anticipate, ask, and advise
      patients about smoking than to assist with and arrange cessation activities.
      Family physicians were more likely than pediatricians to assist and arrange,
      including scheduling follow-up visits to discuss quitting (25.1% vs 11.7%; odds
      ratio [OR], 3.07; 95% confidence interval [CI], 1.22-7.73) and directing nursing
      staff to counsel patients (17.1% vs 10.9%; OR, 3.70; 95% CI, 1.30-10.60). The
      most common perceived barrier to counseling was the belief that children would
      provide inaccurate responses due to either the presence of parents (86.4%) or the
      fear that parents would be notified of their answers (74.0%). Pediatricians
      reported lack of counseling skills as a barrier to providing smoking
      interventions in greater proportion than did family physicians (24.9% vs 54.8%;
      OR, 0.29; 95% CI, 0.14-0.63; P<.001). CONCLUSION: Improvement in smoking
      cessation counseling skills and practices is needed among physicians treating
      children and adolescents.

PMID- 14706965
TI  - Little stories.

PMID- 14706966
TI  - Coffee consumption and risk for type 2 diabetes mellitus.
AB  - BACKGROUND: In small, short-term studies, acute administration of caffeine
      decreases insulin sensitivity and impairs glucose tolerance. OBJECTIVE: To
      examine the long-term relationship between consumption of coffee and other
      caffeinated beverages and incidence of type 2 diabetes mellitus. DESIGN:
      Prospective cohort study. SETTING: The Nurses' Health Study and Health
      Professionals' Follow-up Study. PARTICIPANTS: The authors followed 41 934 men
      from 1986 to 1998 and 84 276 women from 1980 to 1998. These participants did not
      have diabetes, cancer, or cardiovascular disease at baseline. MEASUREMENTS:
      Coffee consumption was assessed every 2 to 4 years through validated
      questionnaires. RESULTS: The authors documented 1333 new cases of type 2 diabetes
      in men and 4085 new cases in women. The authors found an inverse association
      between coffee intake and type 2 diabetes after adjustment for age, body mass
      index, and other risk factors. The multivariate relative risks for diabetes
      according to regular coffee consumption categories (0, <1, 1 to 3, 4 to 5, or >
      or =6 cups per day) in men were 1.00, 0.98, 0.93, 0.71, and 0.46 (95% CI, 0.26 to
      0.82; P = 0.007 for trend), respectively. The corresponding multivariate relative
      risks in women were 1.00, 1.16, 0.99, 0.70, and 0.71 (CI, 0.56 to 0.89; P < 0.001
      for trend), respectively. For decaffeinated coffee, the multivariate relative
      risks comparing persons who drank 4 cups or more per day with nondrinkers were
      0.74 (CI, 0.48 to 1.12) for men and 0.85 (CI, 0.61 to 1.17) for women. Total
      caffeine intake from coffee and other sources was associated with a statistically
      significantly lower risk for diabetes in both men and women. CONCLUSIONS: These
      data suggest that long-term coffee consumption is associated with a statistically
      significantly lower risk for type 2 diabetes.

PMID- 14706967
TI  - The prevalence of nontraditional risk factors for coronary heart disease in
      patients with chronic kidney disease.
AB  - BACKGROUND: Risk for coronary heart disease is high among patients with chronic
      kidney disease. OBJECTIVE: To compare the prevalence of low apolipoprotein A1
      levels and elevated apolipoprotein B, plasma fibrinogen, lipoprotein(a),
      homocysteine, and C-reactive protein levels by estimated glomerular filtration
      rate (GFR). DESIGN: Cross-sectional study. SETTING: Third National Health and
      Nutrition Examination survey. PARTICIPANTS: 12 547, 3180, and 744 persons with
      estimated GFRs of at least 90, 60 to 89, or less than 60 mL/min per 1.73 m2,
      respectively, who were at least 18 years of age. MEASUREMENTS: Chronic kidney
      disease was defined as an estimated GFR of less than 60 mL/min per 1.73 m2 based
      on the abbreviated Modification of Diet in Renal Disease formula. RESULTS: After
      standardization for age, race or ethnicity, and sex, lower estimated GFR (> or
      =90, 60 to 89, or <60 mL/min per 1.73 m2) was associated with lower average
      levels of apolipoprotein A1 (1.44, 1.43, and 1.35 g/L) and higher levels of
      apolipoprotein B (1.03, 1.06, and 1.08 g/L), plasma fibrinogen (8.43, 8.44, and
      9.53 micromol/L), homocysteine (8.5, 10.0, and 13.2 micromol/L), and C-reactive
      protein (3.0, 2.9, and 3.9 mg/L) (P < 0.05 for all values). The multivariate
      adjusted odds ratios of an apolipoprotein A1 level of less than 1.2 g/L, a serum
      lipoprotein(a) level of at least 1.61 micromol/L (> or =45.3 mg/dL), a plasma
      fibrinogen level of at least 10.35 micromol/L, a serum homocysteine level of at
      least 15 micromol/L, and a C-reactive protein level of at least 10.0 mg/L for
      participants with chronic kidney disease compared with those with a GFR of at
      least 90 mL/min per 1.73 m2 or greater were 1.92 (95% CI, 1.02 to 3.63), 1.82
      (CI, 1.06 to 3.13), 1.74 (CI, 1.35 to 2.24), 8.23 (CI, 5.00 to 13.6), and 1.93
      (CI, 1.33 to 2.81), respectively. CONCLUSIONS: Levels of apolipoprotein A1 are
      decreased and levels of homocysteine, lipoprotein(a), fibrinogen, and C-reactive
      protein are increased among patients with chronic kidney disease.

PMID- 14706968
TI  - Differential time to positivity: a useful method for diagnosing catheter-related
      bloodstream infections.
AB  - BACKGROUND: Catheter-related bloodstream infections are associated with
      recognized morbidity and mortality, especially in critically ill patients.
      Accurate diagnosis of such infections results in proper management of patients
      and in reducing unnecessary removal of catheters. OBJECTIVE: To evaluate
      differential time to positivity as a method for diagnosing catheter-related
      bacteremias caused by both short-term and long-term use of central venous
      catheters. DESIGN: Prospective study design. SETTING: M.D. Anderson Cancer
      Center, Houston, Texas, a tertiary care cancer center. PATIENTS: All patients,
      between September 1999 and November 2000, who had the same organism isolated from
      blood cultures drawn simultaneously through the central venous catheter and the
      peripheral vein. MEASUREMENTS: Time necessary for the blood cultures from the
      central venous catheter and the peripheral vein to become positive, as well as
      other relevant patient information. RESULTS: 191 bloodstream infections with
      positive simultaneous central venous catheter and peripheral vein blood cultures
      were included. One hundred eight patients had catheter-related bacteremias, and
      83 had non-catheter-related bacteremias. Catheter-related bacteremias were more
      frequently caused by staphylococci and less likely to be associated with
      underlying hematologic malignant conditions, neutropenia, and longer duration of
      hospitalization. As a diagnostic tool for catheter-related bacteremia (using a
      composite definition reference standard according to the Infectious Diseases
      Society of America guidelines), differential time to positivity of 120 minutes or
      more was associated with 81% sensitivity and 92% specificity for short-term
      catheters and 93% sensitivity and 75% specificity for long-term catheters.
      CONCLUSION: Differential time to positivity of 120 minutes or more is highly
      sensitive and specific for catheter-related bacteremia in patients who have short
      and long-term catheters.

PMID- 14706969
TI  - International prospective study of Klebsiella pneumoniae bacteremia: implications
      of extended-spectrum beta-lactamase production in nosocomial Infections.
AB  - BACKGROUND: Commonly encountered nosocomially acquired gram-negative bacteria,
      especially Klebsiella pneumoniae, produce extended-spectrum beta-lactamases
      (ESBLs) as an antibiotic resistance mechanism. OBJECTIVE: To determine whether
      microbiology laboratories should report the presence of ESBLs and to establish
      the infection-control implications of ESBL-producing organisms. DESIGN:
      Prospective observational study. SETTING: 12 hospitals in South Africa, Taiwan,
      Australia, Argentina, the United States, Belgium, and Turkey. PATIENTS: 440
      patients with 455 consecutive episodes of K. pneumoniae bacteremia between 1
      January 1996 and 31 December 1997; of these, 253 episodes were nosocomially
      acquired. MEASUREMENTS: The K. pneumoniae isolates were examined for the presence
      of ESBLs. Pulsed-field gel electrophoresis was used to analyze the molecular
      epidemiology of nosocomial bacteremia with ESBL-producing K. pneumoniae. RESULTS:
      Overall, 30.8% (78 of 253) episodes of nosocomial bacteremia and 43.5% (30 of 69)
      episodes acquired in intensive care units were due to ESBL-producing organisms.
      After adjustment for potentially confounding variables, previous administration
      of beta-lactam antibiotics containing an oxyimino group (cefuroxime, cefotaxime,
      ceftriaxone, ceftazidime, or aztreonam) was associated with bacteremia due to
      ESBL-producing strains (risk ratio, 3.9 [95% CI, 1.1 to 13.8]). In 7 of 10
      hospitals with more than 1 ESBL-producing isolate, multiple strains with the same
      genotypic pattern were observed, indicating patient-to-patient spread of the
      organism. CONCLUSIONS: Production of ESBLs by Klebsiella pneumoniae is a
      widespread nosocomial problem. Appropriate infection control and antibiotic
      management strategies are needed to stem the spread of this emerging form of
      resistance.

PMID- 14706970
TI  - Patient safety is not enough: targeting quality improvements to optimize the
      health of the population.
AB  - Ensuring patient safety is essential for better health care, but preoccupation
      with niches of medicine, such as patient safety, can inadvertently compromise
      outcomes if it distracts from other problems that pose a greater threat to
      health. The greatest benefit for the population comes from a comprehensive view
      of population needs and making improvements in proportion with their potential
      effect on public health; anything less subjects an excess of people to morbidity
      and death. Patient safety, in context, is a subset of health problems affecting
      Americans. Safety is a subcategory of medical errors, which also includes
      mistakes in health promotion and chronic disease management that cost lives but
      do not affect "safety." These errors are a subset of lapses in quality, which
      result not only from errors but also from systemic problems, such as lack of
      access, inequity, and flawed system designs. Lapses in quality are a subset of
      deficient caring, which encompasses gaps in therapeutics, respect, and compassion
      that are undetected by normative quality indicators. These larger problems
      arguably cost hundreds of thousands more lives than do lapses in safety, and the
      system redesigns to correct them should receive proportionately greater emphasis.
      Ensuring such rational prioritization requires policy and medical leaders to
      eschew parochialism and take a global perspective in gauging health problems. The
      public's well-being requires policymakers to view the system as a whole and
      consider the potential effect on overall population health when prioritizing care
      improvements and system redesigns.

PMID- 14706971
TI  - Following the molecular pathways toward an understanding of the pathogenesis of
      systemic sclerosis.

PMID- 14706972
TI  - Malpractice reform must include steps to prevent medical injury.
AB  - In the current malpractice insurance crisis, physicians have focused their
      advocacy and energy primarily on rapidly increasing liability premiums; problems
      in access to care; and demands for legal reform, especially caps on damages. An
      even more important focus, however, is prevention of injury and improvement of
      patient safety. Physicians largely control patient care and can play a critical
      role in systematically reducing injury. Reforms should go beyond liability
      issues; they should also harness and enhance physicians' ability to act. More
      visible efforts by physicians to reduce harm, better communication with patients
      and others, and true evidence of improved patient safety should reduce patient
      anger and litigiousness. Individually and collectively, physicians can and should
      ensure that "doing no harm" comes first in the malpractice debate.

PMID- 14706974
TI  - Beyond (or back to) traditional risk factors: preventing cardiovascular disease
      in patients with chronic kidney disease.

PMID- 14706973
TI  - A typology of shared decision making, informed consent, and simple consent.
AB  - Enhancing patient choice is a central theme of medical ethics and law. Informed
      consent is the legal process used to promote patient autonomy; shared decision
      making is a widely promoted ethical approach. These processes may most usefully
      be seen as distinct in clinically and ethically important respects. The approach
      outlined in this article uses a model that arrays all medical decisions along 2
      axes: risk and certainty. At the extremes of these continua, 4 decision types are
      produced, each of which constrains the principal actors in predictable ways.
      Shared decision making is most appropriate in situations of uncertainty, in which
      2 or more clinically reasonable alternatives exist. When there is only 1
      realistic choice, patient and physician may gather and exchange information;
      however, the patient cannot be empowered to make choices that do not exist. In
      contrast, informed consent does not require the presence of clinical choice; it
      is appropriate for all decisions of significant risk, even if there is only one
      option. When a clinical decision contains both risk and uncertainty, shared
      decision making and informed consent are both appropriate. For decisions of lower
      risk, consent should still be present, but it can be simple rather than informed.
      Clinicians may use this analysis as a guide to their own interactions with
      patients. In the continuing effort to provide patients with appropriate
      decisional authority over their own medical choices, shared decision making,
      informed consent, and simple consent each has a distinct role to play.

PMID- 14706975
TI  - Catheters, microbes, time, and gold standards.

PMID- 14706976
TI  - Complementary and alternative medical education.

PMID- 14706977
TI  - Complementary and alternative medical education.

PMID- 14706978
TI  - Smallpox vaccination risks and public policy.

PMID- 14706979
TI  - Complementary and alternative medical education.

PMID- 14706980
TI  - Complementary and alternative medical education.

PMID- 14706981
TI  - The future of primary care.

PMID- 14706982
TI  - The future of primary care.

PMID- 14706983
TI  - The future of primary care.

PMID- 14706984
TI  - Hospice benefits and phase I cancer trials.

PMID- 14706985
TI  - Hospice benefits and phase I cancer trials.

PMID- 14706986
TI  - Payment and the future of primary care.

PMID- 14706987
TI  - Alzheimer disease: current concepts and emerging diagnostic and therapeutic
      strategies.

PMID- 14706988
TI  - Diagnostic evaluation of elderly patients with mild memory problems.

PMID- 14706989
TI  - Diagnostic evaluation of elderly patients with mild memory problems.

PMID- 14706990
TI  - Optimized virologic response in hepatitis C virus genotype 4 with peginterferon
      alpha2a and ribavirin.

PMID- 14706991
TI  - Gatifloxacin-induced hepatotoxicity and acute pancreatitis.

PMID- 14706992
TI  - Arm position and blood pressure measurement.

PMID- 14706993
TI  - Summaries for patients. Coffee drinkers at lower risk for type 2 diabetes.

PMID- 14706994
TI  - Summaries for patients. Associations of newer cardiac risk factors with chronic
      kidney disease.

PMID- 14706995
TI  - Summaries for patients. Diagnosing catheter-related bloodstream infections.

PMID- 14706996
TI  - Summaries for patients. Worldwide prevalence of antibiotic resistance in the
      bacteria Klebsiella pneumoniae.

PMID- 14706997
TI  - Risk stratification for noncardiac surgery.

PMID- 14706998
TI  - Risk stratification for noncardiac surgery.

PMID- 14706999
TI  - Pollination ecology and pollination system of Impatiens reptans (Balsaminaceae)
      endemic to China.
AB  - BACKGROUND AND AIMS: China is one of the centres of geographical distribution of
      Impatiens L. Studies of the pollination ecology of this genus in China have,
      until now, been unreported. Impatiens reptans, a species endemic to China, was
      studied. The aims were to examine the pollination ecology and pollination system
      of this species, to compare its pollination ecology with other Impatiens species
      growing in Sumatra and Japan, and to discuss possible reasons for its limited
      distribution. METHODS: The pollination ecology of I. reptans was studied by
      carrying out continuous observations within three naturally growing populations.
      Its pollination system was studied using different pollination methods, marking
      and counting pollen grains, assessing pollen viability and observing pollinator
      behaviour. KEY RESULTS: The flowering phase of the protandrous I. reptans lasted
      for 89 d. The life span of an individual flower was 3.6 d. Primary pollinators
      were honey-bees and bumble-bees. Secondary pollinators were diurnal hawk moths
      and butterflies. Bombus briviceps and Bombus sp. were nectar gatherers. The mean
      nectar sugar concentration was 29.5 %, and the mean value of sucrose/glucose +
      fructose was 0.82. The proportion of seed set ranged from 0.857 to 0.873.
      Distances that seeds were ejected ranged from 0.58 to 1.17 m. Percentage seed
      germination under controlled conditions was 23.1. Pollen viability was highest on
      the day of anthesis and thereafter decreased. Ratios of pollen : ovules ranged
      from 958.8 to 970.6. CONCLUSIONS: Impatiens reptans reproduces by means of cross
      pollination. Its dependence on a specialized habitat, a narrow environmental
      niche, a low percentage of seed germination, and habitat loss could be reasons
      for its limited distribution and endemism.

PMID- 14707000
TI  - The mathematical treatment of leaf venation: the variation in secondary vein
      length along the midrib.
AB  - BACKGROUND AND AIMS: In some dicotyledonous leaves and leaflets, the secondary
      veins run more-or-less straight to the margins and have well-defined lengths. For
      a given half-lamina of length L, an equation, previously proposed, relates the
      lengths of these veins, p, to the distances, l, between the leaf tip and their
      insertions on the midrib: p = B2(x+y)l(x)(L - l)(y)/L(x+y-1), where B, x and y
      are fitted parameters. Aspects of the formula are re-examined, including its
      general applicability, significance and usefulness. METHODS: Length measurements
      were made on leaves of various dicotyledons, notably Ulmus glabra, U. procera,
      Alnus viridis, A. glutinosa, Corylus avellana and Crataegus monogyna. Equations
      were fitted by non-linear regression. KEY RESULTS: The equation has now been
      applied descriptively to 23 species of eight families, but it is sometimes
      preferable or necessary to replace the measured length, L, with a fourth
      parameter that may differ significantly from it. Within a given species, values
      of the indices x and y are positively correlated. Leaves of some U. glabra depart
      qualitatively from the general pattern. As an example of hypothesis testing, the
      equation was used to show that the retuse or emarginate leaf tips of A. glutinosa
      are not due to stunting. CONCLUSIONS; That the equation applies to many species
      suggests that the underlying processes of leaf growth are quantitatively similar.
      Although relevant knowledge of these is scant, consideration of mathematical
      relationships may help their elucidation.

PMID- 14707001
TI  - Light-dependent development of single cell C4 photosynthesis in cotyledons of
      Borszczowia aralocaspica (Chenopodiaceae) during transformation from a storage to
      a photosynthetic organ.
AB  - BACKGROUND AND AIMS: Previous work has shown that Borszczowia aralocaspica
      (Chenopodiaceae) accomplishes C4 photosynthesis in a unique, polarized single
      cell system in leaves. Mature cotyledons have the same structure as leaves, with
      chlorenchyma cells having biochemical polarization of dimorphic chloroplasts and
      C4 functions at opposite ends of the cell. KEY RESULTS: Development of the single
      celled C4 syndrome in cotyledons was characterized. In mature seeds, all cell
      layers are already present in the cotyledons, which contain mostly lipids and
      little starch. The incipient chlorenchyma cells have a few plastids towards the
      centre of the cell. Eight days after germination and growth in the dark, small
      plastids are evenly distributed around the periphery of the expanding cells.
      Immunolocalization studies show slight labelling of Rubisco in plastids in seeds,
      including chlorenchyma, hypodermal and water storage, but not epidermal, cells.
      After imbibition and 8 d of growth in the dark labelling for Rubisco
      progressively increased, being most prominent in chlorenchyma cells. There was no
      immunolabelling for the plastid C4 enzyme pyruvate, Pi dikinase under these
      conditions. Cotyledons developing in light show formation of chlorenchyma tissue,
      induction of the cytosolic enzyme phosphoenolpyruvate carboxylase and development
      of dimorphic chloroplasts at opposite ends of the cells. Proximal chloroplasts
      have well-developed grana, store starch and contain Rubisco; those located
      distally have reduced grana, lack starch and contain pyruvate, Pi dikinase.
      CONCLUSIONS: The results show cotyledons developing in the dark have a single
      structural plastid type which expresses Rubisco, while light induces formation of
      dimorphic chloroplasts from the single plastid pool, synthesis of C4 enzymes, and
      biochemical and structural polarization leading to the single-cell C4 syndrome.

PMID- 14707002
TI  - Fine-scale geographical structure, intra-individual polymorphism and
      recombination in nuclear ribosomal internal transcribed spacers in Armeria
      (Plumbaginaceae).
AB  - BACKGROUND AND AIMS: Isolation and drift are the main causes for geographic
      structure of molecular variation. In contrast, the one found in a previous survey
      in Armeria (Plumbaginaceae) for nuclear ribosomal ITS multicopy regions was
      species-independent and has been hypothesized to be due to extensive gene-flow
      and biased concerted evolution. Since this was inferred from a genus-level
      phylogenetic analysis, the aim of this study was to check for the occurrence of
      such structure and the validity of the proposed model at a local scale, in a
      southern Spanish massif (Sierra Nevada), as well as to examine the evolutionary
      implications at the organism level. METHODS: In addition to 117 sequences of
      direct PCR products from genomic DNA, 50 sequences of PCR products from cloned
      DNA were obtained to analyse cases of intragenomic polymorphisms for the ITS
      regions. KEY RESULTS: Sequence data confirm the occurrence of a species
      independent structure at a local scale and reveal insights through the analysis
      of contact areas between different ITS copies (ribotypes). A comparison between
      cloned and direct sequences (a) confirms that, within these contact areas, ITS
      copies co-occur both in different individuals and within single genomes; and (b)
      reveals recombination between different copies. CONCLUSIONS: This study supports
      the utility of direct sequences for detecting intra-individual polymorphism and
      for partially inferring the ITS copies involved, given previous knowledge of the
      variability. The main evolutionary implication at the organism level is that gene
      flow and concerted evolution shape the geographic structure of ITS variation.

PMID- 14707003
TI  - Population genetic structure of Titanotrichum oldhamii (Gesneriaceae), a
      subtropical bulbiliferous plant with mixed sexual and asexual reproduction.
AB  - BACKGROUND AND AIMS: Titanotrichum oldhamii is a monotypic genus distributed in
      Taiwan, adjacent regions of China and the Ryukyu Isands of Japan. Its
      conservation status is vulnerable as most populations are small and widely
      scattered. Titanotrichum has a mixed system of reproduction with vegetative
      bulbils and seeds. The aim of this study was to understand the population genetic
      structure of Titanotrichum in relation to its specific reproductive behaviour and
      to determine possible implications for conservation strategies. METHODS: After an
      extensive inventory of most wild populations of Titanotrichum in East Asia,
      samples from 25 populations within its major distribution were carried out
      utilizing RAPD and inter-SSR molecular fingerprinting analysis. KEY RESULTS: The
      findings support the conclusion that many populations reproduce predominantly
      asexually but that some genetic variation still exists within populations.
      However, significant amounts of variation exist between populations, perhaps
      reflecting population differentiation by drift. This partitioning of genetic
      diversity indicates that the level of inter-population gene exchange is extremely
      low. These findings are consistent with field observations of very limited seed
      production. The Chinese populations are similar to those of Northern Taiwan,
      while the Ryukyu populations fall within the range of variation of the north
      central Taiwan populations. The Taiwanese populations are relatively variable and
      differentiation between north, east and south Taiwan is evident. CONCLUSIONS: The
      distribution of Titanotrichum seems to be consistent with a former land
      connection between China, Taiwan and the Ryukyu Islands at a glacial maximum
      during the Quaternary, followed by progressive fragmentation of the populations.
      North-central Taiwan is the centre of genetic diversity, possibly due to the
      proximity of the former land bridge between the regions, together with the
      variety of suitable habitats in north Taiwan. The significance of these findings
      for conservation is discussed.

PMID- 14707005
TI  - Lipoxins: endogenous regulators of inflammation.
AB  - Over the past decade, compelling in vivo and in vitro studies have highlighted
      lipoxins (LXs) and aspirin-triggered LXs (ATLs) as endogenously produced anti
      inflammatory eicosanoids. LXs and ATLs elicit distinct anti-inflammatory and
      proresolution bioactions that include inhibition of leukocyte-mediated injury,
      stimulation of macrophage clearance of apoptotic neutrophils, repression of
      proinflammatory cytokine production, modulation of cytokine-stimulated
      metalloproteinase activity, and inhibition of cell proliferation and migration.
      An overview of recent advances in LX physiology is provided, with particular
      emphasis on the cellular and molecular processes involved. These data coupled
      with in vivo models of inflammatory diseases suggest that LX bioactions may be
      amenable to pharmacological mimicry for therapeutic gain.

PMID- 14707004
TI  - Characterization of a lignified secondary phloem fibre-deficient mutant of jute
      (Corchorus capsularis).
AB  - BACKGROUND AND AIMS: High lignin content of lignocellulose jute fibre does not
      favour its utilization in making finer fabrics and other value-added products. To
      aid the development of low-lignin jute fibre, this study aimed to identify a
      phloem fibre mutant with reduced lignin. METHODS: An x-ray-induced mutant line
      (CMU) of jute (Corchorus capsularis) was morphologically evaluated and the
      accession (CMU 013) with the most undulated phenotype was compared with its
      normal parent (JRC 212) for its growth, secondary fibre development and
      lignification of the fibre cell wall. KEY RESULTS: The normal and mutant plants
      showed similar leaf photosynthetic rates. The mutant grew more slowly, had
      shorter internodes and yielded much less fibre after retting. The fibre of the
      mutant contained 50 % less lignin but comparatively more cellulose than that of
      the normal type. Differentiation of primary and secondary vascular tissues
      throughout the CMU 013 stem was regular but it did not have secondary phloem
      fibre bundles as in JRC 212. Instead, a few thin-walled, less lignified fibre
      cells formed uni- or biseriate radial rows within the phloem wedges of the middle
      stem. The lower and earliest developed part of the mutant stem had no lignified
      fibre cells. This developmental deficiency in lignification of fibre cells was
      correlated to a similar deficiency in phenylalanine ammonia lyase activity, but
      not peroxidase activity, in the bark tissue along the stem axis. In spite of
      severe reduction in lignin synthesis in the phloem cells this mutant functioned
      normally and bred true. CONCLUSIONS: In view of the observations made, the mutant
      is designated as deficient lignified phloem fibre (dlpf). This mutant may be
      utilized to engineer low-lignin jute fibre strains and may also serve as a model
      to study the positional information that coordinates secondary wall thickening of
      fibre cells.

PMID- 14707006
TI  - Update of extracellular matrix, its receptors, and cell adhesion molecules in
      mammalian nephrogenesis.
AB  - One of the hallmarks of mammalian nephrogenesis includes a mesenchymal-epithelial
      transition that is accomplished by intercalation of the ureteric bud, an
      epithelium-lined tubelike structure, into an undifferentiated mesenchyme, and the
      latter then undergoes an inductive transformation and differentiates into an
      epithelial phenotype. At the same time, the differentiating mesenchyme
      reciprocates by inducing branching morphogenesis of the ureteric bud, which forms
      a treelike structure with dichotomous iterations. These reciprocal inductive
      interactions lead to the development of a functioning nephron unit made up of a
      glomerulus and proximal and distal tubules. The inductive interactions and
      differentiation events are modulated by a number of transcription factors,
      protooncogenes, and growth factors and their receptors, which regulate the
      expression of target morphogenetic modulators including the ECM, integrin
      receptors, and cell adhesion molecules. These target macromolecules exhibit
      spatiotemporal and stage-specific developmental regulation in the metanephros.
      The ECM molecules expressed at the epithelial-mesenchymal interface are perhaps
      the most relevant and conducive to the paracrine-juxtacrine interactions in a
      scenario where the ligand is expressed in the mesenchyme while the receptor is
      located in the ureteric bud epithelium or vice versa. In addition, expression of
      the target ECM macromolecules is regulated by matrix metalloproteinases and their
      inhibitors to generate a concentration gradient at the interface to further
      propel epithelial-mesenchymal interactions so that nephrogenesis can proceed
      seamlessly. In this review, we discuss and update our current understanding of
      the role of the ECM and related macromolecules with respect to metanephric
      development.

PMID- 14707007
TI  - Heme: a determinant of life and death in renal tubular epithelial cells.
AB  - Heme oxygenase-1 (HO-1) and p21 influence cell fate, and genetic HO-1
      overexpression upregulates p21 and confers resistance to apoptosis. The present
      study examined the effects of heme, a metabolite incriminated in renal injury, on
      sensitivity to apoptosis and cell growth in conjunction with cellular expression
      of HO-1 and p21. Immortalized rat proximal tubular epithelial cells (IRPTCs) were
      exposed to hemin (10 microM) in serum-deplete media (0.1% FBS) and in standard
      cell culture media (5.0% FBS). In the presence of 0.1% FBS media, hemin induced
      p21 through an HO-dependent, p53-independent mechanism; certain products of HO
      activity (iron and carbon monoxide), but not others (ferritin, apoferritin,
      bilirubin), recapitulated these inductive effects on p21 expression. Along with
      this inductive effect on HO-1 and p21, hemin worsened apoptosis, the latter
      exacerbated by the inhibition of HO activity and loss of p21 expression. In
      IRPTCs maintained in 5% FBS, hemin induced HO-dependent p21 expression, provoked
      cell cycle arrest, and inhibited cell growth without inducing apoptosis; this
      inhibitory effect of hemin on cell growth was blocked by the concomitant
      inhibition of HO activity and loss of p21 expression. We conclude that hemin is a
      potent HO-dependent inducer of p21 and that hemin increases the sensitivity to
      apoptosis in serum-deplete conditions and decreases cell growth in serum-replete
      conditions; inhibiting HO activity and concomitantly ablating p21 expression
      exacerbate apoptosis and reverse the growth-inhibitory actions of hemin. We
      suggest that these effects of heme may influence the nature of, and recovery
      from, ischemic and nephrotoxic insults to the kidney.

PMID- 14707008
TI  - Gender, sex hormones, and vascular tone.
AB  - The greater incidence of hypertension and coronary artery disease in men and
      postmenopausal women compared with premenopausal women has been related, in part,
      to gender differences in vascular tone and possible vascular protective effects
      of the female sex hormones estrogen and progesterone. However, vascular effects
      of the male sex hormone testosterone have also been suggested. Estrogen,
      progesterone, and testosterone receptors have been identified in blood vessels of
      human and other mammals and have been localized in the plasmalemma, cytosol, and
      nuclear compartments of various vascular cells, including the endothelium and the
      smooth muscle. The interaction of sex hormones with cytosolic/nuclear receptors
      triggers long-term genomic effects that could stimulate endothelial cell growth
      while inhibiting smooth muscle proliferation. Activation of plasmalemmal sex
      hormone receptors may trigger acute nongenomic responses that could stimulate
      endothelium-dependent mechanisms of vascular relaxation such as the nitric oxide
      cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Additional endothelium
      independent effects of sex hormones may involve inhibition of the signaling
      mechanisms of vascular smooth muscle contraction such as intracellular Ca2+
      concentration and protein kinase C. The sex hormone-induced stimulation of the
      endothelium-dependent mechanisms of vascular relaxation and inhibition of the
      mechanisms of vascular smooth muscle contraction may contribute to the gender
      differences in vascular tone and may represent potential beneficial vascular
      effects of hormone replacement therapy during natural and surgically induced
      deficiencies of gonadal hormones.

PMID- 14707009
TI  - Endo-neuro-endocrine incretin pathways.

PMID- 14707010
TI  - Lower animal conditioning studies help in the understanding of human memory and
      its disorders: the merits of conditioned taste, odor, and flavor aversion
      research.

PMID- 14707011
TI  - Sensory nerves contribute to insulin secretion by glucagon-like peptide-1 in
      mice.
AB  - It has been hypothesized that the potent insulinotropic action of the gut
      incretin hormone glucagon-like peptide-1 (GLP-1) is exerted not only through a
      direct action on the beta cells but may be partially dependent on sensory nerves.
      We therefore examined the influence of GLP-1 in mice rendered sensory denervated
      by neonatal administration of capsaicin performed at days 2 and 5 (50 mg/kg).
      Control mice were given vehicle. Results show that at 10-16 wk of age in control
      mice, intravenous GLP-1 at 0.1 or 10 nmol/kg augmented the insulin response to
      intravenous glucose (1 g/kg) in association with improved glucose elimination. In
      contrast, in capsaicin-pretreated mice, GLP-1 at 0.1 nmol/kg could not augment
      the insulin response to intravenous glucose and no effect on glucose elimination
      was observed. Nevertheless, at the high dose of 10 nmol/kg, GLP-1 augmented the
      insulin response to glucose in capsaicin-pretreated mice as efficiently as in
      control mice. The insulin response to GLP-1 from isolated islets was not affected
      by neonatal capsaicin, and, furthermore, the in vivo insulin response to glucose
      was augmented whereas that to arginine was not affected by capsaicin. It is
      concluded that GLP-1-induced insulin secretion at a low dose in mice is dependent
      on intact sensory nerves and therefore indirectly mediated and that this
      distinguishes GLP-1 from other examined insulin secretagogues.

PMID- 14707012
TI  - Melanocortin receptors mediate the excitatory effects of blood-borne murine
      leptin on hypothalamic paraventricular neurons in rat.
AB  - The central pathways and mediators involved in sympathoexcitatory responses to
      circulating leptin are not well understood, although the arcuate-paraventricular
      nucleus (ARC-PVN) pathway likely plays a critical role. In urethane-anesthetized
      rats, ipsilateral intracarotid artery (ICA) injection of murine leptin (100
      microg/kg) activated most PVN neurons tested. These responses were reduced by
      intracerebroventricular injection of the melanocortin subtype 3 and 4 receptor
      (MC3/4-R) antagonist SHU-9119 (0.6 nmol). The MC3/4-R agonist MTII (0.6 nmol icv)
      activated PVN neurons. Some PVN neurons that were excited by ICA leptin were
      inhibited by local application of neuropeptide Y (NPY, 2.5 ng). ICA leptin (100
      microg/kg) excited presympathetic rostral ventrolateral medulla neurons and renal
      sympathetic nerve activity without significant change in blood pressure or heart
      rate; these effects were mimicked by intracerebroventricular injection of MTII
      (0.6 nmol). These data provide in vivo electrophysiological evidence to support
      the hypothesis that circulating leptin activates the sympathetic nervous system
      by stimulating the release of alpha-melanocyte-stimulating hormone in the
      vicinity of PVN neurons that are inhibited by the orexogenic peptide NPY.

PMID- 14707013
TI  - Rate and extent of compensatory changes in energy intake and expenditure in
      response to altered exercise and diet composition in humans.
AB  - We assessed the effect of no exercise (Nex; control) and high exercise level
      (Hex; approximately 4 MJ/day) and two dietary manipulations [a high-fat diet (HF;
      50% of energy, 700 kJ/100 g) and low-fat diet (LF; 20% of energy, 300 kJ/100 g)]
      on compensatory changes in energy intake (EI) and energy expenditure (EE) over 7
      day periods. Eight lean men were each studied four times in a 2 x 2 randomized
      design. EI was directly quantified by weight of food consumed. EE was assessed by
      heart rate (HR) monitoring. Body weight was measured daily. Mean daily EE was
      17.6 and 11.5 MJ/day (P < 0.001) on the pooled Hex and Nex treatments,
      respectively. EI was higher on HF diets (13.4 MJ/day pooled) compared with the LF
      diets (9.0 MJ/day). Regression analysis showed that these energy imbalances
      induced significant compensatory changes in EB over time of approximately 0.3-0.4
      MJ/day (P < 0.05). These were due to changes in both EI and EE in the opposite
      direction to the perturbation in energy balance. These changes were significant,
      small but persistent, amounting to approximately 0.2 and approximately 0.35
      MJ/day for EI and EE, respectively.

PMID- 14707014
TI  - TRPV4 calcium entry channel: a paradigm for gating diversity.
AB  - The vanilloid receptor-1 (VR1, now TRPV1) was the founding member of a subgroup
      of cation channels within the TRP family. The TRPV subgroup contains six
      mammalian members, which all function as Ca2+ entry channels gated by a variety
      of physical and chemical stimuli. TRPV4, which displays 45% sequence identity
      with TRPV1, is characterized by a surprising gating promiscuity: it is activated
      by hypotonic cell swelling, heat, synthetic 4alpha-phorbols, and several
      endogenous substances including arachidonic acid (AA), the endocannabinoids
      anandamide and 2-AG, and cytochrome P-450 metabolites of AA, such as
      epoxyeicosatrienoic acids. This review summarizes data on TRPV4 as a paradigm of
      gating diversity in this subfamily of Ca2+ entry channels.

PMID- 14707015
TI  - Metabolic syndrome and vascular disease: is nature or nurture leading the new
      epidemic of cardiovascular disease?

PMID- 14707016
TI  - Relative effects of air pollution on lungs and heart.

PMID- 14707017
TI  - Can angiotensin II type 2 receptors have deleterious effects in cardiovascular
      disease? Implications for therapeutic blockade of the renin-angiotensin system.

PMID- 14707018
TI  - Images in cardiovascular medicine. Mediastinal thymoma.

PMID- 14707020
TI  - Effects of carvedilol on left ventricular remodeling after acute myocardial
      infarction: the CAPRICORN Echo Substudy.
AB  - BACKGROUND: The CAPRICORN trial has shown that carvedilol improved outcome in
      patients with left ventricular dysfunction after acute myocardial infarction
      treated with ACE inhibitors. The aim of this substudy was to determine the
      effects of carvedilol on left ventricular remodeling in this patient group.
      METHODS AND RESULTS: Patients entering the CAPRICORN trial from 13 centers in New
      Zealand, Australia, and Spain were recruited for this echocardiographic substudy.
      In 127 patients, quantitative 2D echocardiography was performed according to a
      standard protocol before randomization and repeated after 1, 3, and 6 months of
      treatment with carvedilol or placebo. Left ventricular volumes, ejection fraction
      (Simpson's method), and wall motion score index were determined in a blinded
      analysis at the Core Echo Laboratory. At 6 months, left ventricular end systolic
      volume was 9.2 mL less in the carvedilol group than in the placebo group
      (P=0.023), and left ventricular ejection fraction was 3.9% higher (P=0.015). Left
      ventricular end diastolic volume and wall motion score index were not
      statistically different between the 2 groups at 6 months. CONCLUSIONS: In
      patients with left ventricular dysfunction after acute myocardial infarction
      treated with ACE inhibitors, carvedilol had a beneficial effect on ventricular
      remodeling, which may, in part, mediate the substantial clinical beneficial
      effects of carvedilol in this patient population.

PMID- 14707021
TI  - Response to cardiac arrest and selected life-threatening medical emergencies: the
      medical emergency response plan for schools: A statement for healthcare
      providers, policymakers, school administrators, and community leaders.

PMID- 14707022
TI  - Canadian Trial of Physiological Pacing: Effects of physiological pacing during
      long-term follow-up.
AB  - BACKGROUND: The Canadian Trial of Physiological Pacing (CTOPP) reported that the
      risk of stroke or cardiovascular death was similar between patients receiving
      ventricular versus physiological pacemakers at the end of the original follow-up
      period of 3 years. However, the occurrence of atrial fibrillation was
      significantly less frequent with physiological pacemakers. To assess a potential
      delayed benefit of physiological pacing, follow-up of patients in this study was
      extended to 6 years. METHODS AND RESULTS: A total of 1474 patients requiring a
      pacemaker for symptomatic bradycardia were randomized to receive ventricular and
      1094 to physiological pacemakers. The primary outcome was stroke or
      cardiovascular death. The study was completed in July 1998, and follow-up was
      extended to July 2001. At a mean follow-up of 6.4 years, there was no difference
      between treatment groups in the primary outcome of cardiovascular death or
      stroke. There was no significant difference in total mortality or stroke between
      groups. There was a significantly lower rate of development of atrial
      fibrillation in the physiological group, with a relative risk reduction of 20.1%
      (CI, 5.4 to 32.5; P=0.009). CONCLUSIONS: The CTOPP extended study does not show a
      difference in cardiovascular death or stroke, or in total mortality, or in stroke
      between patients implanted with ventricular or physiological pacemakers over a
      mean follow-up of >6 years. However, there is a persistent significant reduction
      in the development of atrial fibrillation with physiological pacing.

PMID- 14707023
TI  - Novel therapeutic strategy to treat brain ischemia: overexpression of hepatocyte
      growth factor gene reduced ischemic injury without cerebral edema in rat model.
AB  - BACKGROUND: Although cerebral occlusive disease leads to cerebral ischemic
      events, an effective treatment has not yet been established. An ideal therapeutic
      approach to treat ischemia might have both aspects of enhancement of collateral
      formation and prevention of neuronal death. Hepatocyte growth factor (HGF) is a
      potent angiogenic factor that also acts as a neurotrophic factor. Thus, in this
      study, we examined the therapeutic effects of HGF on brain injury in a rat
      permanent middle cerebral artery occlusion model. METHODS AND RESULTS: Gene
      transfer into the brain was performed by injection of human HGF gene with
      hemagglutinating virus of Japan-envelope vector into the cerebrospinal fluid via
      the cisterna magna. Overexpression of the HGF gene resulted in a significant
      decrease in the infarcted brain area as assessed by triphenyltetrazolium chloride
      staining, whereas rats transfected with control vector exhibited a wide area of
      brain death after 24 hours of ischemia. Consistently, the decrease in
      neurological deficit was significantly attenuated in rats transfected with the
      HGF gene at 24 hours after the ischemic event. Stimulation of angiogenesis was
      also detected in rats transfected with the HGF gene compared with controls. Of
      importance, no cerebral edema or destruction of the blood-brain barrier was
      observed in rats transfected with the HGF gene. CONCLUSIONS: Overall, the present
      study demonstrated that overexpression of the HGF gene attenuated brain ischemic
      injury in a rat model, without cerebral edema, through angiogenic and
      neuroprotective actions. In particular, the reduction of brain injury by HGF may
      provide a new therapeutic option to treat cerebrovascular disease.

PMID- 14707024
TI  - G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide
      synthase in cultured human endothelial cells.
AB  - BACKGROUND: Impaired insulin-mediated vasodilation might contribute to vascular
      damage in insulin-resistant states. Little is known about insulin regulation of
      nitric oxide (NO) synthesis in insulin-resistant cells. The aim of this work was
      to investigate insulin regulation of NO synthesis in human umbilical vein
      endothelial cells (HUVECs) carrying the IRS-1 gene G972R variant, known to be
      associated with impaired insulin activation of the PI3-kinase (PI3-K) pathway in
      transfected cells. METHODS AND RESULTS: HUVECs were screened for the presence of
      the G972R-IRS-1 (HUVEC-G972R) variant by restriction fragment length
      polymorphisms. After 24-hour exposure to 10(-7) mol/L insulin, endothelial NO
      synthase (eNOS) mRNA (reverse transcription-polymerase chain reaction), eNOS
      protein levels (Western blotting), and NOS activity (conversion of [(3)H]arginine
      into [(3)H]citrulline) were increased in wild-type HUVECs (HUVEC-WT), whereas
      they did not change from baseline in HUVEC-G972R. Compared with HUVEC-WT, in
      HUVEC-G972R after 2 and 10 minutes of insulin stimulation, IRS-1-associated PI3-K
      activity was reduced by 47% and 32%, respectively; Akt phosphorylation was
      decreased by 40% at both time points; and eNOS-Ser1177 phosphorylation was
      reduced by 38% and 51%, respectively. In HUVEC-WT, eNOS-Thr495 phosphorylation
      decreased after insulin stimulation. In contrast, in HUVEC-G972R, eNOS-Thr495
      phosphorylation increased after insulin stimulation and was 40% greater than in
      HUVEC-WT. CONCLUSIONS: Our data demonstrate that genetic impairment of the (IRS)
      1/PI3-K/PDK-1/Akt insulin signaling cascade determines impaired insulin
      stimulated NO release and suggest that the G972R-IRS-1 polymorphism, through a
      direct impairment of Akt/eNOS activation in endothelial cells, may contribute to
      the genetic predisposition to develop endothelial dysfunction and cardiovascular
      disease.

PMID- 14707025
TI  - Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon
      of clopidogrel resistance.
AB  - BACKGROUND: Interindividual variability of platelet inhibition after aspirin or
      clopidogrel administration has been described. Additionally, aspirin resistance
      and clopidogrel resistance occur in some individuals. Because the prodrug
      clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized
      that interindividual variability in clopidogrel efficacy might be related to
      interindividual differences in CYP3A4 metabolic activity. METHODS AND RESULTS:
      Platelet aggregation was measured before and after clopidogrel treatment in 32
      patients undergoing coronary artery stent implantation and in 35 healthy
      volunteers. The erythromycin breath test was used to measure CYP3A4 activity in
      vivo in 25 of the healthy volunteers. Individual platelet aggregation was studied
      in 10 healthy volunteers after the coadministration of clopidogrel and rifampin
      (a CYP3A4 inducer). Clopidogrel nonresponders, low responders, and responders
      were defined by a relative inhibition of adenosine diphosphate (20 micromol/L)
      induced platelet aggregation of <10%, 10% to 29%, and > or =30%, respectively.
      Among patients, 22% were clopidogrel nonresponders, 32% were low responders, and
      47% were responders. Among volunteers, 16% were nonresponders, 12% were low
      responders, and 72% were responders. Percent platelet aggregation after
      clopidogrel inversely correlated with CYP3A4 activity (r=-0.6, P=0.003). Improved
      platelet inhibition in volunteers resistant to clopidogrel was observed with the
      coadministration of clopidogrel and rifampin. CONCLUSIONS: Clopidogrel
      administration results in interindividual variability in platelet inhibition,
      which correlates with CYP3A4 metabolic activity. Measurement of antiplatelet drug
      efficacy with a point-of-care device and alternative antithrombotic strategies
      for aspirin or clopidogrel nonresponders and low responders could reduce the
      incidence of thrombotic events that continue to occur despite oral antiplatelet
      therapy.

PMID- 14707026
TI  - Pulmonary vein denervation enhances long-term benefit after circumferential
      ablation for paroxysmal atrial fibrillation.
AB  - BACKGROUND: There are no data to evaluate the relationship between autonomic
      nerve function modification and recurrent atrial fibrillation (AF) after
      circumferential pulmonary vein ablation (CPVA). This study assesses the
      incremental benefit of vagal denervation by radiofrequency in preventing
      recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF.
      METHODS AND RESULTS: Data were collected on 297 patients undergoing CPVA for
      paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein
      ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3%
      of patients. Follow-up ended at 12 months. Heart rate variability attenuation,
      consistent with vagal withdrawal, was detectable for up to 3 months after CPVA,
      particularly in patients with reflexes and CVD, who were less likely to have
      recurrent AF than those without reflexes (P=0.0002, log-rank test). Only the
      percentage area of left atrial isolation and CVD were predictors of AF recurrence
      after CPVA (P<0.001 and P=0.025, respectively). CONCLUSIONS: This study suggests
      that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12
      months.

PMID- 14707027
TI  - Developmental control of titin isoform expression and passive stiffness in fetal
      and neonatal myocardium.
AB  - Developmental changes in contractile behavior are known to occur during fetal and
      postnatal heart development. In this study, we examined whether adaptations take
      place in titin. A range of species was used to evaluate titin isoform expression
      and altered function during cardiac muscle development. A novel titin exon
      microarray that allows all 363 titin exons to be monitored simultaneously was
      used for transcript studies. Results reveal expression of fetal titin isoforms,
      characterized by additional spring elements both in the tandem Ig and PEVK region
      of the molecule. At the protein level, the fetal cardiac isoform predominates in
      fetal and neonatal myocardium and gradually disappears during postnatal
      development with a time course that varies in different species. Passive
      myocardium, contrary to previous reports, was found to be less stiff in the
      neonate than in the adult. This can be explained by the unique spring composition
      of fetal cardiac titin expressed by the neonate. Changes in titin expression are
      likely to impact functional transitions and diastolic filling behavior during
      development of the heart.

PMID- 14707028
TI  - Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes.
AB  - Recently, environmental chemicals have appeared in daily human life, and these
      chemicals have been incidentally taken in by humans. The serum concentrations of
      some of these chemicals have been found to be associated with the onset and
      incidence rate of diabetes mellitus. It has been suggested that one of the
      environmental chemicals, bisphenol A (BPA), has hormone-like activity. It has
      also been demonstrated that some hormones affect insulin resistance and fat
      distribution in the body. To study the effects of these environmental chemicals
      on glucose metabolism, the effect of BPA on glucose transport in mouse 3T3-F442A
      adipocytes was investigated. The 3T3-F442A adipocytes were incubated with various
      concentrations of BPA in a medium. Deoxyglucose uptake assay was performed with
      and without insulin. Immunoblot analysis was performed with a glucose transporter
      (GLUT) 4-specific antibody and antiphosphotyrosine antibody. The BPA treatment
      enhanced basal and insulin-stimulated glucose uptake, and caused an increased
      amount of GLUT4 protein. Thus, the enhanced glucose uptake resulting from the BPA
      treatment was at least partially due to the increased amount of GLUT4. Tyrosine
      phosphorylation of insulin receptor substrate-1 with insulin stimulation was not
      significantly affected. In conclusion, it was demonstrated that BPA, one of the
      chemicals that we intake incidentally, affects the glucose transport in
      adipocytes, and also that the environmental chemicals may be identified as one of
      the environmental factors that affect diabetes and obesity.

PMID- 14707029
TI  - Oleamide is a selective endogenous agonist of rat and human CB1 cannabinoid
      receptors.
AB  - 1. The ability of the endogenous fatty acid amide, cis-oleamide (ODA), to bind to
      and activate cannabinoid CB(1) and CB(2) receptors was investigated. 2. ODA
      competitively inhibited binding of the nonselective cannabinoid agonist
      [(3)H]CP55,940 and the selective CB(1) antagonist [(3)H]SR141716A to rat whole
      brain membranes with K(i) values of 1.14 microm (0.52-2.53 microm, Hill
      slope=0.80, n=6) and 2.63 microm (0.62-11.20 microm, Hill slope=0.92, n=4),
      respectively. AEA inhibited [(3)H]CP55,940 binding in rat whole-brain membranes
      with a K(i) of 428 nm (346-510 nm, Hill slope=-1.33, n=3). 3. ODA competitively
      inhibited [(3)H]CP55,940 binding in human CB(1) (hCB(1)) cell membranes with a
      K(i) value of 8.13 microm (4.97-13.32 microm, n=2). In human CB(2) transfected
      (hCB(2)) HEK-293T cell membranes, 100 microm ODA produced only a partial (42.5+/
      7%) inhibition of [(3)H]CP55,940 binding. 4. ODA stimulated [(35)S]GTPgammaS
      binding in a concentration-dependent manner (EC(50)=1.64 microm (0.29-9.32
      microm), R(2)=0.99, n=4-9), with maximal stimulation of 188+/-9% of basal at 100
      microm. AEA stimulated [(35)S]GTPgammaS binding with an EC(50) of 10.43 microm
      (4.45-24.42 microm, R(2)=1.00, n=3, 195+/-4% of basal at 300 microm). Trans
      oleamide (trans-ODA) failed to significantly stimulate [(35)S]GTPgammaS binding
      at concentrations up to 100 microm. 5. ODA (10 microm)-stimulated
      [(35)S]GTPgammaS binding was reversed by the selective CB(1) antagonist SR141716A
      (IC(50)=2.11 nm (0.32-13.77 nm), R(2)=1.00, n=6). 6. The anatomical distribution
      of ODA-stimulated [(35)S]GTPgammaS binding in rat brain sections was
      indistinguishable from that of HU210. Increases of similar magnitude were
      observed due to both agonists in the striatum, cortex, hippocampus and
      cerebellum. 7. ODA (10 microm) significantly inhibited forskolin-stimulated
      cyclic AMP (cAMP) accumulation in mouse neuroblastoma N1E 115 cells (P=0.02,
      n=11). ODA-mediated inhibition was completely reversed by 1 microm SR141716A
      (P<0.001, n=11) and was also reversed by pretreatment with 300 ng ml(-1)
      pertussis toxin (P<0.001, n=6). 8. These data demonstrate that ODA is a full
      cannabinoid CB(1) receptor agonist. Therefore, in addition to allosteric
      modulation of other receptors and possible entourage effects due to fatty acid
      amide hydrolase inhibition, the effects of ODA may be mediated directly via the
      CB(1) receptor.

PMID- 14707030
TI  - Contribution of nitric oxide produced by inducible nitric oxide synthase to
      vascular responses of mesenteric arterioles in streptozotocin-diabetic rats.
AB  - 1. The functional changes in mesenteric arterioles of streptozotocin-induced
      diabetes were investigated by intravital microscopy. The mesentery was
      exteriorized from anesthetized rats, spread in a chamber, and superfused with
      Tyrode solution. All drugs tested were applied to the superfusing Tyrode
      solution. 2. Compared with age-matched controls, the diabetic rats showed
      enhanced vascular sensitivity to phenylephrine, an alpha(1)-adrenoceptor agonist.
      The preincubation of the mesentery with N(G)-nitro-l-arginine (l-NNA), a nitric
      oxide synthase (NOS) inhibitor, shifted the phenylephrine-concentration-response
      curves to the left in both the diabetic and control rats. Even in the presence of
      l-NNA, the sensitivity to phenylephrine was higher in the diabetic rats than in
      the control. 3. Acetylcholine relaxed the mesenteric arterioles in both groups,
      but to a significantly greater extent in the control than in the diabetic rats.
      However, the l-NNA-induced constriction of arterioles did not differ
      significantly between the groups. In contrast, the amplitude of the constrictions
      of mesenteric arterioles induced by S-ethylisothiourea, an inducible NOS (iNOS)
      inhibitor, was significantly greater in the diabetic rats than in the control. 4.
      Immunostaining of the mesentery with a specific antibody for iNOS revealed iNOS
      in the microvessels of only the diabetic rats. 5. These results suggest that
      constrictor responses to alpha(1)-adrenoceptor stimulation are sensitized in the
      mesenteric arterioles of STZ-diabetic rats, and that iNOS expressed in the
      arteriolar smooth muscle plays a role in suppressing the basal tone and the
      reactivity of the arterioles in STZ-diabetic rats.

PMID- 14707031
TI  - Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use.
AB  - Impaired drug metabolism is a major cause of adverse drug reactions, and it is
      often caused by mutations at genes coding for drug-metabolising enzymes. Two
      amino-acid polymorphisms of cytochrome P4502C9 (CYP2C9), an enzyme involved in
      the metabolism of several nonsteroidal anti-inflammatory drugs (NSAIDs), were
      studied in 94 individuals with acute bleeding after NSAIDs use and 124
      individuals receiving NSAIDs with no adverse effects. The frequency of CYP2C9
      variant alleles was increased in overall bleeding patients, with a significant
      trend to higher risk with increasing number of variant alleles (P=0.02). The odds
      ratio for bleeding patients receiving CYP2C9 substrates (n=33) was 2.5 for
      heterozygous and 3.7 for homozygous carriers of mutations (P<0.015), suggesting
      that the inherited impairment of CYP2C9 activity increases the risk for severe
      adverse drug reactions after NSAIDs use.

PMID- 14707032
TI  - Review of prevalence data in, and evaluation of methods for cross cultural
      adaptation of, UK surveys on tobacco and alcohol in ethnic minority groups.
AB  - OBJECTIVE: To assess the adequacy of cross cultural adaptations of survey
      questions on self reported tobacco and alcohol consumption in the United Kingdom.
      DESIGN: Assessment of consistency of data between studies identified through
      literature review. Studies evaluated with 12 guidelines developed from the
      research literature on achieving cross cultural comparability. RESULTS: The
      literature review identified 18 key studies, five of them on national samples.
      Survey instruments were obtained for 15 of these. The comparison of prevalence
      data in national surveys showed some important discrepancies, greater for tobacco
      than for alcohol. For example, prevalence of cigarette smoking in Bangladeshi
      women was 6% in a national survey in 1994 and 1% in a national survey in 1999; in
      Chinese men it was 31% in a survey in 1993-4 and 17% in one in 1999; in African
      Caribbean men it was 29% in a 1992 survey and 42% in one in 1993-4. The most
      guidelines met by any study was three, although one study partly met a fourth.
      Two studies met no guidelines. Only four studies consulted with ethnic minority
      communities in developing the questionnaire, none checked each language version
      with all others, and two stated the questionnaire had not been validated.
      CONCLUSIONS: Surveys have not followed best practice in relation to measurement
      of risk factors in cross cultural settings. There is inconsistency in the
      prevalence data on smoking provided by different major national UK studies. Users
      of such data should be aware of their limitations. Research is needed to help
      achieve linguistic equivalence of survey questions in cross cultural research.

PMID- 14707034
TI  - Atheroprotection in the abence of "caves": is it the fat, the vessels, or both?

PMID- 14707035
TI  - From fat fighter to risk factor: the zigzag trek of leptin.

PMID- 14707036
TI  - Matrix management: assigning different roles for MMP-2 and MMP-9 in vascular
      remodeling.

PMID- 14707037
TI  - Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP
      cyclohydrolase I overexpression reduces endothelial dysfunction and
      atherosclerosis in ApoE-knockout mice.
AB  - OBJECTIVE: Increased production of reactive oxygen species and loss of
      endothelial nitric oxide (NO) bioactivity are key features of vascular disease
      states such as atherosclerosis. Tetrahydrobiopterin (BH4) is a required cofactor
      for NO synthesis by endothelial nitric oxide synthase (eNOS); pharmacologic
      studies suggest that reduced BH4 availability may be an important mediator of
      endothelial dysfunction in atherosclerosis. We aimed to investigate the
      importance of endothelial BH4 availability in atherosclerosis using a transgenic
      mouse model with endothelial-targeted overexpression of the rate-limiting enzyme
      in BH4 synthesis, GTP-cyclohydrolase I (GTPCH). METHODS AND RESULTS: Transgenic
      mice were crossed into an ApoE knockout (ApoE-KO) background and fed a high-fat
      diet for 16 weeks. Compared with ApoE-KO controls, transgenic mice (ApoE-KO/GCH
      Tg) had higher aortic BH4 levels, reduced endothelial superoxide production and
      eNOS uncoupling, increased cGMP levels, and preserved NO-mediated endothelium
      dependent vasorelaxations. Furthermore, aortic root atherosclerotic plaque was
      significantly reduced in ApoE-KO/GCH-Tg mice compared with ApoE-KO controls.
      CONCLUSIONS: These findings indicate that BH4 availability is a critical
      determinant of eNOS regulation in atherosclerosis and is a rational therapeutic
      target to restore NO-mediated endothelial function and reduce disease
      progression.

PMID- 14707038
TI  - Adipophilin enhances lipid accumulation and prevents lipid efflux from THP-1
      macrophages: potential role in atherogenesis.
AB  - OBJECTIVE: Uptake of modified low-density lipoprotein (LDL) by macrophages
      through scavenger receptors results in lipid droplets accumulation and foam cell
      formation. Excess lipid deposition in macrophages has been reported to modulate
      expression of several genes including adipophilin. In this study, we investigated
      the function of adipophilin in lipid accumulation and cholesterol efflux in THP-1
      macrophages. METHODS AND RESULTS: Adipophilin mRNA expression was 3.5-fold higher
      in human atherosclerotic plaques compared with healthy areas of the same
      arteries. Moreover, in the presence of acetylated LDL (AcLDL), triglycerides and
      cholesteryl esters were increased in macrophages overexpressing adipophilin by
      40% and 67%, respectively, whereas their accumulation was reduced when endogenous
      cellular adipophilin was depleted using siRNA approach. In addition, neither
      overexpression nor downregulation of adipophilin altered expression of genes
      involved in lipid efflux. However, the affinity and the number of AcLDL receptors
      were not affected. After 24-hour incubation of lipid-loaded macrophages with
      apolipoprotein A-I, cholesterol efflux was reduced by 47% in adipophilin
      transfected cells versus control cells. CONCLUSIONS: Our results showed that
      stimulation of adipophilin expression in macrophages by modified LDL promotes
      triglycerides and cholesterol storage and reduces cholesterol efflux. Therefore,
      adipophilin might contribute, in vivo, to lipid accumulation in the intima of the
      arterial wall.

PMID- 14707039
TI  - Covalently-bound heparin makes collagen thromboresistant.
AB  - OBJECTIVE: Blood compatibility of artificial surfaces depends on their
      immunogenic and thrombogenic properties. Collagen's weak antigenicity makes it an
      attractive candidate for stent coatings or fabrication of vascular grafts.
      However, the thrombogenic nature of collagen limits its application. We examined
      whether heparinization can make collagen more thromboresistant. METHODS AND
      RESULTS: Collagen was heparinized by crosslinking collagen with extensively
      periodate oxidized heparin and/or by covalently bonding of mildly periodate
      oxidized heparin. Both ways of heparinization have no effect on platelet adhesion
      and could not abolish induction of platelet procoagulant activity. However,
      thrombin generation was completely prevented under static and flow conditions.
      The functionality of immobilized heparin was confirmed by specific uptake of
      antithrombin, 13.5+/-4.7 pmol/cm2 and 1.95+/-0.21 pmol/cm2 for mildly and heavily
      periodated heparin, respectively. CONCLUSIONS: These results indicate that
      immobilization of heparin on collagen, even as a crosslinker, is a very effective
      way to prevent surface thrombus formation. These data encourage the application
      of heparinized collagen as stent-graft material in animal and eventually human
      studies.

PMID- 14707040
TI  - C-peptide colocalizes with macrophages in early arteriosclerotic lesions of
      diabetic subjects and induces monocyte chemotaxis in vitro.
AB  - OBJECTIVE: Increased levels of C-peptide, a cleavage product of proinsulin,
      circulate in patients with insulin resistance and early type 2 diabetes, a high
      risk population for the development of a diffuse and extensive pattern of
      arteriosclerosis. This study tested the hypothesis that C-peptide might
      participate in atherogenesis in these patients. METHOD AND RESULTS: We
      demonstrate significantly higher intimal C-peptide deposition in thoracic aorta
      specimens from young diabetic subjects compared with matched nondiabetic controls
      as determined by immunohistochemical staining. C-peptide colocalized with
      monocytes/macrophages in the arterial intima of artery specimen from diabetic
      subjects. In vitro, C-peptide stimulated monocyte chemotaxis in a concentration
      dependent manner with a maximal 2.3+/-0.4-fold increase at 1 nmol/L C-peptide.
      Pertussis toxin, wortmannin, and LY294002 inhibited C-peptide-induced monocyte
      chemotaxis, suggesting the involvement of pertussis toxin-sensitive G-proteins as
      well as a phosphoinositide 3-kinase (PI3K)-dependent mechanism. In addition, C
      peptide treatment activated PI3K in human monocytes, as demonstrated by PI3K
      activity assays. CONCLUSIONS: C-peptide accumulated in the vessel wall in early
      atherogenesis in diabetic subjects and may promote monocyte migration into
      developing lesions. These data support the hypothesis that C-peptide may play an
      active role in atherogenesis in diabetic patients and suggest a new mechanism for
      accelerated arterial disease in diabetes.

PMID- 14707041
TI  - Transduction of the N-terminal fragments of MYPT1 enhances myofilament Ca2+
      sensitivity in an intact coronary artery.
AB  - OBJECTIVE: The region of the 110 kDa regulatory subunit (MYPT1) of smooth muscle
      myosin phosphatase involved in the regulation of contraction was determined under
      physiological conditions. METHODS AND RESULTS: Using HIV Tat protein-mediated
      protein transduction, the N-terminal fragments of MYPT1 were introduced to the
      intact porcine coronary arterial strips. Pre-incubation with 3 micromol/L TAT
      MYPT1(1-374), a construct containing the Tat peptide and the residues 1 to 374 of
      MYPT1, for 15 minutes augmented (2.4-fold) the subsequent contraction induced by
      adding 1.25 mmol/L of extracellular Ca2+ under 118 mmol/L K+ depolarization, with
      no augmentation of the [Ca2+]i elevation. The deletion of the Tat peptide,
      MYPT1(1-374), abolished the augmenting effect. TAT-MYPT1(1-296) demonstrated a
      weaker but significant augmentation (1.7-fold). However, TAT-MYPT1(1-171), TAT
      MYPT1(39-374), TAT-MYPT1(39-296), and TAT-MYPT1(297-374) had no augmenting
      activity. The myosin light chain phosphorylation level as a function of
      extracellular Ca2+ concentrations was shifted to the left in the strips
      pretreated with TAT-MYPT1(1-374) compared with the control. CONCLUSIONS: Region 1
      to 296 was the minimal region involved in the enhancement of contraction, and
      region 297 to 374 played a supplemental role. These results suggested that the
      interaction mainly between catalytic subunit and MYPT1 play a critical role in
      the regulation of the endogenous myosin phosphatase in intact smooth muscle.

PMID- 14707042
TI  - Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3
      by lipopolysaccharide.
AB  - IFN-regulatory factor 3 (IRF3) is known to participate in the transcriptional
      induction of chemokines and cytokines, including IFNs, as a result of viral or
      bacterial infection. In this study, we demonstrate that the LPS-mediated
      activation of IRF3 and subsequent induction of chemokine genes or IRF3-responsive
      reporter constructs are inhibited after exposure of human or murine macrophages
      to the Bacillus anthracis toxin lethal factor. The inhibitory effect is caused by
      interference with the activation of the stress-activated protein kinase, p38, due
      to a proteolytic cleavage of mitogen-activated protein kinase kinase 6, and can
      be overcome by the ectopic expression of a cleavage-resistant mutant of mitogen
      activated protein kinase kinase 6 or a constitutively active IRF3. The lethal
      factor-mediated inhibition of IRF3 activation and subsequent cytokine production
      through bacterial membrane components offers Bacillus anthracis an efficient
      mechanism to evade the innate immune response.

PMID- 14707043
TI  - Cutting edge: NF-kappa B2 is a negative regulator of dendritic cell function.
AB  - RelB, a member of the NF-kappaB family of transcription factors, is essential for
      dendritic cell (DC) maturation. Recent findings indicate that RelB is exclusively
      regulated through its interaction with cytoplasmic NF-kappaB2/p100. The studies
      presented in this report show that DCs lacking NF-kappaB2 have dramatically
      enhanced RelB activity, associated with increased MHC class II and costimulatory
      molecule expression and an enhanced ability to induce CD4(+) T cell responses.
      These studies identify a novel role for NF-kappaB2 in the negative regulation of
      RelB-induced DC maturation, with critical consequences for the regulation of
      adaptive immune responses.

PMID- 14707044
TI  - Cutting edge: novel priming of tumor-specific immunity by NKG2D-triggered NK cell
      mediated tumor rejection and Th1-independent CD4+ T cell pathway.
AB  - NKG2D is an activation receptor on NK cells and has been demonstrated as a
      primary cytotoxicity receptor for mouse NK cells. Primary rejection of class I
      deficient RMA-S lymphoma cells expressing the NKG2D ligand, retinoic acid early
      inducible-1beta, was critically dependent upon NK cell perforin and occurred
      independently of T cells. NKG2D-triggered NK cell rejection of RMA-S-retinoic
      acid early inducible-1beta tumor primed a secondary tumor-specific T cell
      response mediated by both CD4+ and CD8+ T cells in the effector phase.
      Surprisingly, during the priming phase, CD4+ T cells, but not CD8+ T cells, were
      also required to generate this secondary T cell immunity; however, T cell priming
      was independent of Th1 cytokines, such as IFN-gamma and IL-12. These data imply a
      novel pathway for priming T cell immunity, that is, stimulated upon NK cell
      mediated cytotoxicity of NKG2D ligand-expressing tumor cells, dependent upon CD4+
      T cells in the primary phase, and independent of conventional Th1-type immunity.

PMID- 14707045
TI  - Cutting edge: BAFF regulates CD21/35 and CD23 expression independent of its B
      cell survival function.
AB  - Herein we demonstrate that B cell-activating factor of the TNF family (BAFF), a B
      cell survival factor, also regulates CD21/35 and CD23 expression. BAFF blockade
      in wild-type mice down-modulates CD21/35 and CD23 on B cells while survival
      remains intact, and BAFF exposure causes elevated CD21/35 and CD23 expression.
      Similar down-modulation is observed in bcl-2-transgenic mice treated with a BAFF
      inhibitor. This is the first evidence that BAFF has a function independent of B
      cell survival. Reports using CD21/35 and CD23 expression to assess splenic B cell
      subsets in BAFF-null mice concluded a lack of B cells beyond the immature stage.
      Since CD21/35 and CD23 are inadequate for delineating B cell subpopulations in
      BAFF-null mice, we used expression of BAFF-R and several B cell markers to
      identify more mature splenic B cells in these mice. These data broaden our
      understanding of BAFF function and correct the view that BAFF-null mice lack
      mature B cells.

PMID- 14707046
TI  - Differential role of CCR2 in islet and heart allograft rejection: tissue
      specificity of chemokine/chemokine receptor function in vivo.
AB  - Chemokines have a pivotal role in the mobilization and activation of specific
      leukocyte subsets in acute allograft rejection. However, the role of specific
      chemokines and chemokine receptors in islet allograft rejection has not been
      fully elucidated. We now show that islet allograft rejection is associated with a
      steady increase in intragraft expression of the chemokines CCL8 (monocyte
      chemoattractant protein-2), CCL9 (monocyte chemoattractant protein-5), CCL5
      (RANTES), CXCL-10 (IFN-gamma-inducible protein-10), and CXCL9 (monokine induced
      by IFN-gamma) and their corresponding chemokine receptors CCR2, CCR5, CCR1, and
      CXCR3. Because CCR2 was found to be highly induced, we tested the specific role
      of CCR2 in islet allograft rejection by transplanting fully MHC mismatched islets
      from BALB/c mice into C57BL/6 wild-type (WT) and CCR2-deficient mice (CCR2-/-). A
      significant prolongation of islet allograft survival was noted in CCR2-/-
      recipients, with median survival time of 24 and 12 days for CCR2-/- and WT
      recipients, respectively (p < 0.0001). This was associated with reduction in the
      generation of CD8+, but not CD4+ effector alloreactive T cells
      (CD62L(low)CD44(high)) in CCR2-/- compared with WT recipients. In addition, CCR2
      /- recipients had a reduced Th1 and increased Th2 alloresponse in the periphery
      (by ELISPOT analysis) as well as in the grafts (by RT-PCR). However, these
      changes were only transient in CCR2-/- recipients that ultimately rejected their
      grafts. Furthermore, in contrast to the islet transplants, CCR2 deficiency
      offered only marginal prolongation of heart allograft survival. This study
      demonstrates the important role for CCR2 in early islet allograft rejection and
      highlights the tissue specificity of the chemokine/chemokine receptor system in
      vivo in regulating allograft rejection.

PMID- 14707047
TI  - Enhanced priming of antigen-specific CTLs in vivo by embryonic stem cell-derived
      dendritic cells expressing chemokine along with antigenic protein: application to
      antitumor vaccination.
AB  - Dendritic cell (DC)-based immunotherapy is regarded as a promising means for anti
      cancer therapy. The efficiency of T cell-priming in vivo by transferred DCs
      should depend on their encounter with T cells. In the present study, we attempted
      to improve the capacity of DCs to prime T cells in vivo by genetic modification
      to express chemokine with a T cell-attracting property. For genetic modification
      of DCs, we used a recently established method to generate DCs from mouse
      embryonic stem cells. We generated double-transfectant DCs expressing a chemokine
      along with a model Ag (OVA) by sequential transfection of embryonic stem cells,
      and then induced differentiation to DCs. We comparatively evaluated the effect of
      three kinds of chemokines; secondary lymphoid tissue chemokine (SLC), monokine
      induced by IFN-gamma (Mig), and lymphotactin (Lptn). All three types of double
      transfectant DCs primed OVA-specific CTLs in vivo more efficiently than did DCs
      expressing only OVA, and the coexpression of SLC or Lptn was more effective than
      that of Mig. Immunization with DCs expressing OVA plus SLC or Mig provided
      protection from OVA-expressing tumor cells more potently than did immunization
      with OVA alone, and SLC was more effective than Mig. In contrast, coexpression of
      Lptn gave no additive effect on protection from the tumor. Collectively, among
      the three chemokines, expression of SLC was the most effective in enhancing
      antitumor immunity by transferred DCs in vivo. The findings provide useful
      information for the development of a potent DC-based cellular immunotherapy.

PMID- 14707048
TI  - CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and
      prevention of thyroiditis.
AB  - CD7 and CD28 are T cell Ig superfamily molecules that share common signaling
      mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte
      development and function, we have generated CD7/CD28-double-deficient mice. CD7-
      and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of
      CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient
      mice had decreased CD4+CD25+ T cells in spleen compared with wild-type mice, and
      CD7/CD28-double-deficient mice had decreased numbers of CD4+CD25+ T cells in both
      thymus and spleen compared with both wild-type and CD28-deficient mice.
      Functional studies demonstrated that CD4+CD25+ T cells from CD28-deficient and
      CD7/CD28-double-deficient mice could mediate suppression of CD3 mAb activation of
      CD4+CD25- wild-type T cells, but were less potent than wild-type CD4+CD25+ T
      regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice
      (>1 year) that was not seen in age-matched control mice or single CD7- or CD28
      deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for
      the development of spontaneous thyroiditis. Taken together, these data
      demonstrated collaborative roles for both CD7 and CD28 in determination of number
      and function of CD4+CD25+ T regulatory cells in the thymus and peripheral immune
      sites and in the development of spontaneous thyroiditis.

PMID- 14707049
TI  - TCR-independent and caspase-independent apoptosis of murine thymocytes by CD24
      cross-linking.
AB  - CD24, also referred to as the heat-stable Ag, is a T cell differentiation Ag that
      is highly expressed on both CD4-CD8- double negative and CD4+CD8+ double positive
      thymocytes. Here, we report that CD24 ligation by a new anti-CD24 Ab, mT-20,
      induced the apoptosis of both double negative and double positive thymocytes, as
      well as the Scid.adh thymic lymphoma cell line, in the absence of TCR/CD3
      engagement. CD24-mediated apoptosis of mouse thymocytes and its signaling pathway
      appeared not to be associated with p53, CD95, TNFR, or caspases. Furthermore, we
      found that cell death was blocked by the addition of scavengers of reactive
      oxygen species or by Bcl-2 overexpression, implying the role of CD24 signaling in
      the mitochondrial regulation. In this study, we suggest that CD24 ligation
      induced the apoptosis of immature thymocytes independently of both caspase and
      TCR.

PMID- 14707050
TI  - Marginal zone, but not follicular B cells, are potent activators of naive CD4 T
      cells.
AB  - The early involvement of marginal zone (MZ) B lymphocytes in T-independent immune
      responses is well established. In this study we compared the abilities of MZ and
      follicular (FO) B cells to collaborate with T cells. After immunization with
      soluble hen egg lysozyme, both MZ and FO B cells captured Ag and migrated to T
      cell areas in the response to hen egg lysozyme. MZ B cells were far superior to
      FO B cells in inducing CD4+ T cell expansion both in vitro and in vivo. MZ, but
      not FO, B cells, after interaction with T cells, differentiated into plasma
      cells, and in addition they stimulated Ag-specific CD4+ T cells to produce high
      levels of Th1-like cytokines upon primary stimulation in vitro. These results
      indicate that MZ B cells rapidly and effectively capture soluble Ag and activate
      CD4+ T cells to become effector T cells. The enhanced capacity of MZ B cells to
      prime T cells in this study appeared to be intrinsic to MZ B cells, as both MZ
      and FO B cell populations express an identical Ag receptor.

PMID- 14707051
TI  - TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and
      reveals a predisposition to B cell lymphoma.
AB  - TNF is well characterized as a mediator of inflammatory responses. TNF also
      facilitates organization of secondary lymphoid organs, particularly B cell
      follicles and germinal centers, a hallmark of T-dependent Ab responses. TNF also
      mediates defense against tumors. We examined the role of TNF in the development
      of inflammatory autoimmune disorders resembling systemic lupus erythematosus and
      Sjogren's syndrome induced by excess B cell-activating factor belonging to the
      TNF family (BAFF), by generating BAFF-transgenic (Tg) mice lacking TNF. TNF(-/-)
      BAFF-Tg mice resembled TNF(-/-) mice, in that they lacked B cell follicles,
      follicular dendritic cells, and germinal centers, and have impaired responses to
      T-dependent Ags. Nevertheless, TNF(-/-) BAFF-Tg mice developed autoimmune
      disorders similar to that of BAFF-Tg mice. Disease in TNF(-/-) BAFF-Tg mice
      correlates with the expansion of transitional type 2 and marginal zone B cell
      populations and enhanced T-independent immune responses. TNF deficiency in BAFF
      Tg mice also led to a surprisingly high incidence of B cell lymphomas (>35%),
      which most likely resulted from the combined effects of BAFF promotion of
      neoplastic B cell survival, coupled with lack of protective antitumor defense by
      TNF. Thus, TNF appears to be dispensable for BAFF-mediated autoimmune disorders
      and may, in fact, counter any proneoplastic effects of high levels of BAFF in
      diseases such as Sjogren's syndrome, systemic lupus erythematosus, and rheumatoid
      arthritis.

PMID- 14707052
TI  - Progressive surface B cell antigen receptor down-regulation accompanies efficient
      development of antinuclear antigen B cells to mature, follicular phenotype.
AB  - Previous studies have suggested that B cell Ag receptor (BCR) down-regulation by
      potentially pathological autoreactive B cells is associated with pathways leading
      to developmental arrest and receptor editing, or anergy. In this study we compare
      the primary development of B cells in two strains of mice expressing transgenic
      BCRs that differ by a single amino acid substitution that substantially increases
      reactivity for nuclear autoantigens such as DNA. Surprisingly, we find that both
      BCRs promote efficient development to mature follicular phenotype, but the
      strongly autoreactive BCR fails to promote marginal zone B cell development. The
      follicular B cells expressing the strongly autoreactive BCR do not appear to be
      anergic, as they robustly respond to polyclonal stimuli in vitro, are not short
      lived, and can participate in germinal center reactions. Strikingly however,
      substantial and progressive down-modulation of surface IgM and IgD takes place
      throughout their primary development in the BM and periphery. We propose that BCR
      autoantigen interactions regulate this pathway, resulting in reduced cellular
      avidity for autoantigens. This process of "learned ignorance" could allow
      autoreactive B cells access to the foreign Ag-driven memory B cell response,
      during which their self-reactivity would be attenuated by somatic hypermutation
      and selection in the germinal center.

PMID- 14707053
TI  - TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T
      cell activity in both humans and mice.
AB  - In previous studies, we have shown that murine CD4+CD25+ regulatory T cells
      produce high levels of TGF-beta1 in a cell surface and/or secreted form, and
      blockade of such TGF-beta1 by anti-TGF-beta curtails the ability of these cells
      to suppress CD25- T cell proliferation and B cell Ig production in in vitro
      suppressor assays. In further support for the role of TGF-beta1 in suppression by
      CD4+CD25+ T cells, we show in this study that another TGF-beta1-blocking
      molecule, recombinant latency-associated peptide of TGF-beta1 (rLAP), also
      reverses suppression by mouse CD4+CD25+ T cells as well as their human
      counterparts, CD4+CD25(high) T cells. In addition, we show that CD25- T cells
      exposed to CD4+CD25+ T cells in vitro manifest activation of Smad-2 and induction
      of CD103, the latter a TGF-beta-inducible surface integrin. In further studies,
      we show that while CD4+CD25+ T cells from TGF-beta1-deficient mice can suppress
      CD25- T cell proliferation in vitro, these cells do not protect recipient mice
      from colitis in the SCID transfer model in vivo, and, in addition, CD4+LAP+, but
      not CD4+LAP- T cells from normal mice protect recipient mice from colitis in this
      model. Together, these studies demonstrate that TGF-beta1 produced by CD4+CD25+ T
      cells is involved in the suppressor activity of these cells, particularly in
      their ability to regulate intestinal inflammation.

PMID- 14707054
TI  - Ephrin-A1 suppresses Th2 cell activation and provides a regulatory link to lung
      epithelial cells.
AB  - Gene expression screening showed decreased ephrin-A1 expression in CD4+ T cells
      of asthma patients. Ephrin-A1 is the ligand of the Eph receptor family of
      tyrosine kinases, forming the largest family of receptor tyrosine kinases. Their
      immune regulatory properties are largely unknown. This study demonstrates
      significantly reduced ephrin-A1 expression in T cells of asthma patients using
      real time-PCR. Immunohistological analyses revealed strong ephrin-A1 expression
      in lung tissue and low expression in cortical areas of lymph nodes. It is absent
      in T cell/B cell areas of the spleen. Colocalization of ephrin-A1 and its
      receptors was found only in the lung, but not in lymphoid tissues. In vitro
      activation of T cells reduced ephrin-A1 at mRNA and protein levels. T cell
      proliferation, activation-induced, and IL-2-dependent cell death were inhibited
      by cross-linking ephrin-A1, and not by engagement of Eph receptors. However, anti
      EphA1 receptor slightly enhances Ag-specific and polyclonal proliferation of PBMC
      cultures. Furthermore, activation-induced CD25 up-regulation was diminished by
      ephrin-A1 engagement. Ephrin-A1 engagement reduced IL-2 expression by 82% and IL
      4 reduced it by 69%; the IFN-gamma expression remained unaffected. These results
      demonstrate that ephrin-A1 suppresses T cell activation and Th2 cytokine
      expression, while preventing activation-induced cell death. The reduced ephrin-A1
      expression in asthma patients may reflect the increased frequency of activated T
      cells in peripheral blood. That the natural ligands of ephrin-A1 are most
      abundantly expressed in the lung may be relevant for Th2 cell regulation in
      asthma and Th2 cell generation by mucosal allergens.

PMID- 14707055
TI  - Central tolerance to self-antigen expressed by cortical epithelial cells.
AB  - The exposure of developing thymocytes to high-affinity self-Ag results in T cell
      tolerance. A predominant mechanism for this is clonal deletion; though receptor
      editing, anergy induction, and positive selection of regulatory T cells have also
      been described. It is unclear what signals are involved in determining different
      tolerance mechanisms. In particular, OT-I mice displayed receptor editing when
      the high-affinity self-Ag was expressed in cortical epithelial cells (cEC) using
      the human keratin 14 promoter. To test the hypothesis that receptor editing is a
      consequence of a unique instruction given by cEC presenting self-Ag, we created
      mice expressing the 2C and HY ligands under control of the keratin 14 promoter.
      Alternatively, we studied the fate of developing T cells in OT-I mice where Ag
      was presented by all thymic APC. Surprisingly, we found that the tolerance
      mechanism was not influenced by the APC subset involved in presentation. Clonal
      deletion was observed in 2C and HY models even when Ag was presented only by cEC;
      and receptor editing was observed in OT-I mice even when Ag was presented by all
      thymic APC. These results suggest that different TCRs show intrinsic differences
      in thymic tolerance mechanism.

PMID- 14707056
TI  - Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed
      skin: role for tissue microenvironment and dendritic cells in establishment of T
      cell-homing subsets.
AB  - The effector/memory T cell pool branches in homing subsets selectively
      trafficking to organs such as gut or skin. Little is known about the critical
      factors in the generation of skin-homing CD8+ T cells, although they are crucial
      effectors in skin-restricted immune responses such as contact hypersensitivity
      and melanoma defense. In this study, we show that intracutaneous, but not i.v.
      injection of bone marrow-derived dendritic cells induced skin-homing CD8+ T cells
      with up-regulated E-selectin ligand expression and effector function in contact
      hypersensitivity. The skin-homing potential and E-selectin ligand expression
      remained stable in memory phase without further Ag contact. In contrast, i.p.
      injection induced T cells expressing the gut-homing integrin alpha(4)beta(7).
      Although differential expression of these adhesion molecules was strictly
      associated with the immunization route, the postulated skin-homing marker CCR4
      was transiently up-regulated in all conditions. Interestingly, dendritic cells
      from different tissues effectively induced the corresponding homing markers on T
      cells in vitro. Our results suggest a crucial role for the tissue
      microenvironment and dendritic cells in the instruction of T cells for tissue
      selective homing and demonstrate that Langerhans cells are specialized to target
      T cells to inflamed skin.

PMID- 14707057
TI  - Turnover and proliferation of NK cells in steady state and lymphopenic
      conditions.
AB  - To gain insight into NK cell dynamics, we investigated the turnover and
      proliferation rates of NK cells in normal and lymphopenic conditions. In contrast
      to previous reports suggesting a very rapid turnover of NK cells, continuous 5
      bromo-2'-deoxyuridine (BrdU)-labeling studies demonstrated that the time
      necessary for labeling 50% of splenic NK cells in mature mice was 17 days,
      similar to the rate of labeling of memory T cells. In contrast, in young mice,
      splenic NK cells labeled very rapidly with BrdU, although cell cycle analyses and
      BrdU pulse-labeling studies suggested that most of this proliferation occurred in
      a precursor population. A somewhat larger percentage of bone marrow NK cells was
      cycling, suggesting that these proliferating cells are the precursors of the
      mostly nondividing or slowly dividing splenic NK cells. Splenic NK cells from
      mature mice also did not proliferate significantly when transferred to normal
      mice, but did proliferate when transferred to irradiated mice. Thus, NK cells,
      like T cells, undergo homeostatic proliferation in a lymphopenic environment.
      Homeostatic proliferation of NK cells was not dependent on host cell class I
      molecules or host production of IL-15. Nevertheless, the number of recovered NK
      cells was much lower in IL-15(-/-) hosts. These results suggest that IL-15 is not
      essential for homeostatic proliferation of NK cells, but is necessary for
      survival of the NK cells. Our results provide important basic information
      concerning the production and replacement of NK cells.

PMID- 14707058
TI  - MHC class II molecules play a role in the selection of autoreactive class I
      restricted CD8 T cells that are essential contributors to type 1 diabetes
      development in nonobese diabetic mice.
AB  - Development of autoreactive CD4 T cells contributing to type 1 diabetes (T1D) in
      both humans and nonobese diabetic (NOD) mice is either promoted or dominantly
      inhibited by particular MHC class II variants. In addition, it is now clear that
      when co-expressed with other susceptibility genes, some common MHC class I
      variants aberrantly mediate autoreactive CD8 T cell responses also essential to
      T1D development. However, it was unknown whether the development of diabetogenic
      CD8 T cells could also be dominantly inhibited by particular MHC variants. We
      addressed this issue by crossing NOD mice transgenically expressing the TCR from
      the diabetogenic CD8 T cell clone AI4 with NOD stocks congenic for MHC haplotypes
      that dominantly inhibit T1D. High numbers of functional AI4 T cells only
      developed in controls homozygously expressing NOD-derived H2(g7) molecules. In
      contrast, heterozygous expression of some MHC haplotypes conferring T1D
      resistance anergized AI4 T cells through decreased TCR (H2(b)) or CD8 expression
      (H2(q)). Most interestingly, while AI4 T cells exert a class I-restricted
      effector function, H2(nb1) MHC class II molecules can contribute to their
      negative selection. These findings provide insights to how particular MHC class I
      and class II variants interactively regulate the development of diabetogenic T
      cells and the TCR promiscuity of such autoreactive effectors.

PMID- 14707059
TI  - Innate immune discrimination of apoptotic cells: repression of proinflammatory
      macrophage transcription is coupled directly to specific recognition.
AB  - Physiological cell death is a process the purpose of which is the elimination of
      functionally inappropriate cells in a manner that does not elicit an inflammatory
      response. We have shown previously that the ability of apoptotic corpses to be
      recognized by macrophages and to modulate the proinflammatory responses of those
      cells represents paradoxically a gain-of-function acquired during the
      physiological cell death process. Cells that die pathologically (that is,
      necrotic vs apoptotic corpses) also are recognized by macrophages but do not down
      regulate macrophage inflammatory responses; the recognition of these two classes
      of native dying cells occurs via distinct and noncompeting mechanisms. We have
      examined the apoptotic modulation of proinflammatory cytokine gene transcription
      in macrophages (by real-time RT-PCR analysis) and the corresponding modulation of
      transcriptional activators (by transcriptional reporter analyses). Our data
      demonstrate that apoptotic cells target the proinflammatory transcriptional
      machinery of macrophages with which they interact, without apparent effect on
      proximal steps of Toll-like receptor signaling. The modulatory activity of the
      corpse is manifest as an immediate-early inhibition of proinflammatory cytokine
      gene transcription, and is exerted directly upon binding to the macrophage,
      independent of subsequent engulfment and soluble factor involvement. Recognition
      and inflammatory modulation represent key elements of an innate immune response
      that discriminates live from effete cells, and without regard to self.

PMID- 14707060
TI  - Dual role of CCR2 during initiation and progression of collagen-induced
      arthritis: evidence for regulatory activity of CCR2+ T cells.
AB  - Chemokines play an important role in the recruitment of leukocytes and have
      recently been shown to also attract regulatory T cells. Using blocking mAbs, we
      analyzed the role of the chemokine receptor CCR2 during initiation and
      progression of collagen-induced arthritis in mice. Blockade of CCR2 from days 0
      to 15 markedly improved clinical signs of arthritis and histological scores
      measuring leukocyte infiltration, synovial hyperplasia, and bone and cartilage
      erosion. CCR2 blockade during disease initiation significantly reduced plasma
      titers of collagen Abs in vivo. In vitro CCR2 blockade also interfered with
      collagen-specific activation and proliferation of T cells. Surprisingly, CCR2
      blockade from days 21 to 36 markedly aggravated clinical and histological signs
      of arthritis and increased the humoral immune response against collagen. We show
      that CCR2 is expressed on regulatory T cells. Purified CCR2+ T cells are fully
      anergic toward polyclonal and collagen-specific activation and potently suppress
      activation of other T and B cells. The subpopulation of CCR2+ CD25+ regulatory T
      cells increases approximately 5-fold in the progression phase, while CCR2
      expression on other leukocyte populations remains unchanged. These findings
      identify CCR2+ T cells as regulatory T cells and indicate that CCR2 also plays an
      important role in down-modulating an inflammatory response.

PMID- 14707061
TI  - NKp44 triggers NK cell activation through DAP12 association that is not
      influenced by a putative cytoplasmic inhibitory sequence.
AB  - NKp44 (NCR2) is a member of the natural cytotoxicity receptor (NCR) family that
      is expressed on activated human NK cells. We dissected structural attributes of
      NKp44 to determine their contributions to receptor function. Our results
      demonstrate that surface expression and NK cell activation by NKp44 is mediated
      through noncovalent association with the immunoreceptor tyrosine-based activation
      motif-containing protein, DAP12. Physical linkage to DAP12 requires lysine-183 in
      the NKp44 transmembrane domain. Intriguingly, the cytoplasmic domain of NKp44
      also contains a sequence that matches the immunoreceptor tyrosine-based
      inhibitory motif (ITIM) consensus. By expressing a chimeric receptor in an NK
      like cell line, we found that this ITIM-like motif from NKp44 lacks inhibitory
      capacity in a redirected cytotoxicity assay. The NKp44 cytoplasmic tyrosine was
      efficiently phosphorylated in the chimeric receptor upon treating the cells with
      pervanadate, but it was unable to recruit ITIM-binding negative effector
      phosphatases. We also generated NK-like cell lines expressing epitope-tagged wild
      type or tyrosine to phenylalanine mutant (Y238F) versions of NKp44 and compared
      their capacities to induce activation marker expression, promote IFN-gamma
      production, or stimulate target cell cytotoxicity. We did not detect any tyrosine
      dependent reduction or enhancement of NK cell activation through wild-type vs.
      Y238F mutant NKp44. Finally, the cytoplasmic tyrosine-based sequence did not
      provide a docking site for the AP-2 clathrin adaptor, nor did it potentiate
      receptor internalization. In summary, all activating properties and surface
      expression of NKp44 are mediated through its association with DAP12, and the
      putative ITIM in the NKp44 cytoplasmic domain does not appear to attenuate
      activating function.

PMID- 14707062
TI  - Invariant chain and the MHC class II cytoplasmic domains regulate localization of
      MHC class II molecules to lipid rafts in tumor cell-based vaccines.
AB  - Cell-based tumor vaccines, consisting of MHC class I+ tumor cells engineered to
      express MHC class II molecules, stimulate tumor-specific CD4+ T cells to mediate
      rejection of established, poorly immunogenic tumors. Previous experiments have
      demonstrated that these vaccines induce immunity by functioning as APCs for
      endogenously synthesized, tumor-encoded Ags. However, coexpression of the MHC
      class II accessory molecule invariant chain (Ii), or deletion of the MHC class II
      cytoplasmic domain abrogates vaccine immunogenicity. Recent reports have
      highlighted the role of lipid microdomains in Ag presentation. To determine
      whether Ii expression and/or truncation of MHC class II molecules impact vaccine
      efficacy by altering MHC class II localization to lipid microdomains, we examined
      the lipid raft affinity of MHC class II molecules in mouse M12.C3 B cell
      lymphomas and SaI/A(k) sarcoma vaccine cells. Functional MHC class II
      heterodimers were detected in lipid rafts of both cell types. Interestingly,
      expression of Ii in M12.C3 cells or SaI/A(k) cells blocked the MHC class II
      interactions with cell surface lipid rafts. In both cell types, truncation of
      either the alpha- or beta-chain decreased the affinity of class II molecules for
      lipid rafts. Simultaneous deletion of both cytoplasmic domains further reduced
      localization of class II molecules to lipid rafts. Collectively, these data
      suggest that coexpression of Ii or deletion of the cytoplasmic domains of MHC
      class II molecules may reduce vaccine efficacy by blocking the constitutive
      association of MHC class II molecules with plasma membrane lipid rafts.

PMID- 14707063
TI  - An altered self-peptide with superagonist activity blocks a CD8-mediated mouse
      model of type 1 diabetes.
AB  - T cell tolerance can be experimentally induced through administration of self
      peptides with single amino acid substitution (altered peptide ligands or APLs).
      However, little is known about the effects of APLs on already differentiated
      autoreactive CD8+ T cells that play a pivotal role in the pathogenesis of
      autoimmune diabetes. We generated a panel of APLs derived from an influenza virus
      hemagglutinin peptide exhibiting in vitro functions ranging from antagonism to
      superagonism on specific CD8+ T cells. A superagonist APL was further
      characterized for its therapeutic activity in a transgenic mouse model of type 1
      diabetes. When injected i.v. 1 day after the transfer of diabetogenic
      hemagglutinin-specific CD8+ T cells into insulin promoter-hemagglutinin
      transgenic mice, the superagonist APL proved more effective than the native
      hemagglutinin peptide in blocking diabetes. This protective effect was associated
      with an inhibition of CD8+ T cell cytotoxicity in vivo and with a decreased
      accumulation of these cells in the pancreas, leading to a marked reduction of
      intrainsulitis. In conclusion, a superagonist "self-peptide" APL was more
      effective than the native peptide in treating a CD8+ T cell-mediated diabetes
      model.

PMID- 14707064
TI  - Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25
      CD4+ precursors in a thymus-independent process.
AB  - The capacity of naturally occurring autoreactive CD25+CD4+ regulatory T cells
      (Treg) to control immune responses both in vivo and in vitro is now well
      established. It has been demonstrated that these cells undergo positive selection
      within the thymus and appear to enter the periphery as committed CD25+CD4+ Treg.
      We have shown previously that CD25+CD4+ Treg with the capacity to prevent skin
      allograft rejection can be generated by pretreatment with donor alloantigen under
      the cover of anti-CD4 therapy. Here we demonstrate that this process does not
      require an intact thymus. Furthermore, generation of these Treg is not dependent
      on the expansion of CD25+CD4+ thymic emigrants, because depletion of CD25+ cells
      before pretreatment does not prevent Treg development, and Treg can be generated
      from CD25-CD4+ precursors. Taken together, these results clearly demonstrate that
      CD25+CD4+ Treg can be generated in the periphery from CD25-CD4+ precursors in a
      pathway distinct to that by which naturally occurring autoreactive CD25+CD4+ Treg
      develop. These observations may have important implications for the design of
      protocols, both experimental and clinical, for the induction of tolerance to
      autoantigens or alloantigens in adults with limited thymic function.

PMID- 14707065
TI  - TCR vaccines against a murine T cell lymphoma: a primary role for antibodies of
      the IgG2c class in tumor protection.
AB  - Tumor-associated proteins can act as effective immunotherapeutic targets.
      Immunization with tumor TCR protein conjugated to the immunogenic protein keyhole
      limpet hemocyanin (KLH) protects mice from tumor challenge with the murine T cell
      lymphoma C6VL. The immune mechanisms responsible for this tumor protection are of
      interest for designing more effective vaccine strategies. Previous studies using
      depletion experiments had suggested a CD8-mediated component of protection
      induced by TCR-KLH vaccines. In this study we used CD8alpha knockout, micro MT,
      and FcgammaR knockout mice to investigate the relative roles of CD8+ T cells and
      Ab in protective immunity induced by TCR-KLH immunization. We found that CD8+ T
      cells are not required for tumor protection, although they may contribute to
      protection. Vaccine-induced Abs are sufficient to mediate protection against this
      murine T cell lymphoma through an FcR-dependent mechanism. This was confirmed
      with Ab transfers, which protect challenged mice. Additionally, recombinase
      activating gene 1(-/-) splenocytes can mediate Ab-dependent cellular cytotoxicity
      against this tumor in the presence of bound anti-TCR Abs. IFN-gamma knockout mice
      demonstrated a requirement for IFN-gamma, probably via generation of IgG2c Abs,
      in vaccine-induced tumor protection. IFN-gamma knockout mice were not protected
      by immunization and had a severe impairment in IgG2c Ab production in response to
      immunization. Although mock-depleted anti-TCR Abs could transfer tumor
      protection, IgG2c-deficient anti-TCR Abs were unable to transfer tumor protection
      to wild-type mice. These results suggest that TCR-KLH vaccine-induced tumor
      protection in the C6VL system is primarily attributable to the induction of IgG2c
      Abs and humoral immunity.

PMID- 14707066
TI  - Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK
      cells.
AB  - Autoimmune (type 1) diabetes results from a loss of beta cells that is mediated
      by self-reactive T cells. Previous studies have shown that a single injection of
      CFA prevents diabetes in nonobese diabetic (NOD) mice, but the mechanism(s) of
      protection remain unknown. We show here that NOD mice immunized with CFA have a
      markedly reduced incidence of diabetes and that this reduced incidence is
      associated with a decrease in the number of beta cell-specific, autoreactive CTL.
      In addition, the adoptive transfer of diabetes into syngeneic NOD/SCID recipients
      was prevented by CFA immunization, and the protective effects of CFA were lost
      when cells expressing the NK cell marker, asialo GM1, were removed from both
      donor cells and recipient mice. Returning a population of CD3-DX5+ cells to the
      adoptive transfer restored the protective effects of CFA. Therefore, NK cells
      mediate the protective effects of CFA possibly through the down-regulation of
      autoreactive CTL and stimulation of NK cells represents a novel approach to the
      prevention of autoimmune diabetes.

PMID- 14707067
TI  - Dissociation of NKT stimulation, cytokine induction, and NK activation in vivo by
      the use of distinct TCR-binding ceramides.
AB  - NKT and NK cells are important immune regulatory cells. The only efficient means
      to selectively stimulate NKT cells in vivo is alpha-galactosylceramide
      (alphaGalCer). However, alphaGalCer effectively stimulates and then diminishes
      the number of detectable NKT cells. It also exhibits a potent, indirect ability
      to activate NK cells. We have now discovered another ceramide compound, beta
      galactosylceramide (betaGalCer) (C12), that efficiently diminishes the number of
      detectable mouse NKT cells in vivo without inducing significant cytokine
      expression or activation of NK cells. Binding studies using CD1d tetramers loaded
      with betaGalCer (C12) demonstrated significant but lower intensity binding to NKT
      cells when compared with alphaGalCer, but both ceramides were equally efficient
      in reducing the number of NKT cells. However, betaGalCer (C12), in contrast to
      alphaGalCer, failed to increase NK cell size, number, and cytolytic activity.
      Also in contrast to alphaGalCer, betaGalCer (C12) is a poor inducer of IFN-gamma,
      TNF-alpha, GM-CSF, and IL-4 gene expression. These qualitative differences in NKT
      perturbation/NK activation have important implications for delineating the unique
      in vivo roles of NKT vs NK cells. Thus, alphaGalCer (which triggers NKT cells and
      activates NK cells) efficiently increases the resistance to allogeneic bone
      marrow transplantation while betaGalCer (C12) (which triggers NKT cells but does
      not activate NK cells) fails to enhance bone marrow graft rejection. Our results
      show betaGalCer (C12) can effectively discriminate between NKT- and NK-mediated
      responses in vivo. These results indicate the use of different TCR-binding
      ceramides can provide a unique approach for understanding the intricate
      immunoregulatory contributions of these two cell types.

PMID- 14707068
TI  - IL-12p70-dependent Th1 induction by human B cells requires combined activation
      with CD40 ligand and CpG DNA.
AB  - The detection of microbial molecules via Toll-like receptors (TLR) in B cells is
      not well characterized. In this study, we found that both naive and memory B
      cells lack TLR4 (receptor for LPS) but express TLR9 (receptor for CpG motifs) and
      produce IL-6, TNF-alpha, and IL-10 upon stimulation with CpG oligonucleotides
      (ODN), synthetic mimics of microbial DNA. Consistent with the lack of TLR4,
      purified B cells failed to respond to LPS. Similar to CpG ODN, CD40 ligand
      (CD40L) alone induced IL-6, TNF-alpha, and IL-10. Production of these cytokines
      as well as IgM synthesis was synergistically increased when both CpG ODN and
      CD40L were combined. Unlike IL-6, TNF-alpha, and IL-10, the Th1 cytokine IL-12p70
      was detected only when both CpG ODN and CD40L were present, and its induction was
      independent of B cell receptor cross-linking. CpG ODN did not increase the
      capacity of CD40L-activated B cells to induce proliferation of naive T cells.
      However, B cells activated with CpG ODN and CD40L strongly enhanced IFN-gamma
      production in developing CD4 T cells via IL-12. Together, these results
      demonstrate that IL-12p70 production in human B cells is under the dual control
      of microbial stimulation and T cell help. Our findings provide a molecular basis
      for the potent adjuvant activity of CpG ODN to support humoral immune responses
      observed in vivo, and for the limited value of LPS.

PMID- 14707069
TI  - Early growth response gene 3 regulates thymocyte proliferation during the
      transition from CD4-CD8- to CD4+CD8+.
AB  - In thymocytes developing in the alphabeta lineage, the transition from CD4, CD8
      double negative (DN) to CD4, CD8 double positive (DP) is associated with several
      rounds of cell division and changes in the expression of multiple genes. This
      transition is induced by the formation of a pre-TCR that includes a rearranged
      TCR beta-chain and the pre-TCR alpha-chain. The mechanism by which the pre-TCR
      influences both gene expression and proliferation has not been defined. We have
      evaluated the role played by early growth response gene 3 (Egr3) in translating
      pre-TCR signals into differentiation and proliferation. Egr3 is a transcriptional
      regulator that contains a zinc-finger DNA binding domain. We find that Egr3
      deficient mice have a reduced number of thymocytes compared with wild-type mice,
      and that this is due to poor proliferation during the DN to DP transition.
      Treatment of both Egr3(+/+) and Egr3(-/-) mice on the Rag1(-/-) background with
      anti-CD3epsilon Ab in vivo results in similar differentiation events, but reduced
      cell recovery in the Egr3(-/-) mice. We have also generated transgenic mice that
      express high levels of Egr3 constitutively, and when these mice are bred onto a
      Rag1(-/-) background they exhibit increased proliferation in the absence of
      stimulation and have pre-TCR alpha-chain and CD25 down-regulation, as well as
      increased Calpha expression. The results show that Egr3 is an important regulator
      of proliferation in response to pre-TCR signals, and that it also may regulate
      some specific aspects of differentiation.

PMID- 14707070
TI  - The cell surface-localized heat shock protein 70 epitope TKD induces migration
      and cytolytic activity selectively in human NK cells.
AB  - Profiling of surface-bound proteins uncovers a tumor-selective heat shock protein
      70 (Hsp70) membrane expression that provides a target structure for human NK
      cells. Hsp70 peptide TKD (TKDNNLLGRFELSG; aa 450-463) was found to enhance the
      cytolytic activity of NK cells. In this study, we demonstrate that TKD-activated
      CD3-CD56+CD94+ NK cells are selectively attracted by Hsp70 membrane-positive
      tumor cells, and supernatants derived thereof. Hsp70 membrane-negative tumors
      failed to attract these NK cells. The capacity to migrate was associated with a
      substantial lytic activity against Hsp70-positive tumor cells. Because NK cell
      migration was independent of cell-to-cell contact, the involvement of a soluble
      factor was assumed. Interestingly, synthetic Hsp70 protein and Hsp70 peptide TKD,
      mimicking surface-bound Hsp70, initiates migration of NK cells in a concentration
      dependent (1-5 microg/ml), highly selective, and chemokine-independent manner. In
      summary, our results indicate that Hsp70 peptide TKD not only stimulates
      cytolysis but also chemotaxis in CD3-CD56+CD94+ NK cells.

PMID- 14707071
TI  - A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8
      T cell response to influenza in vivo.
AB  - 4-1BBL(-/-) mice exhibit normal primary CD8 T cell responses to influenza virus,
      but show decreased CD8 T cell numbers late in the primary response as well as
      decreased secondary responses. In contrast, CD28(-/-) mice are defective in
      initial CD8 T cell expansion. Using agonistic anti-4-1BB Ab to replace the CD28
      or 4-1BB signal, we examined the timing of the required signals for CD28 vs 4-1BB
      costimulation. A single dose of agonistic anti-4-1BB Ab added only during priming
      restores the secondary CD8 T cell response in CD28(-/-) mice. Once the T cell
      numbers in the primary response reach a minimum threshold, a full secondary
      response is achieved even in the absence of CD28. In contrast, anti-4-1BB added
      during priming fails to correct the defective secondary response in 4-1BBL(-/-)
      mice, whereas addition of anti-4-1BB during challenge fully restores this
      response. Thus, there is a switch in costimulatory requirement from CD28 to 4-1BB
      during primary vs recall responses. Adoptive transfer studies show that T cells
      primed in 4-1BBL(-/-) or wild-type mice are equally capable of re-expansion when
      rechallenged in wild-type mice. These studies rule out a model in which signals
      delivered through 4-1BB during priming program the T cells to give a full recall
      response and suggest that 4-1BB-4-1BBL interactions take place at later stages in
      the immune response. The results indicate that anti-4-1BB or 4-1BBL therapy will
      be most effective during the boost phase of a prime-boost vaccination strategy.

PMID- 14707072
TI  - Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in
      cancer is mediated by reactive oxygen species.
AB  - Tumor growth is associated with the accumulation of immature myeloid cells (ImC),
      which in mice are characterized by the expression of Gr-1 and CD11b markers.
      These cells suppress Ag-specific CD8+ T cells via direct cell-cell contact.
      However, the mechanism of immunosuppressive activity of tumor-derived ImC remains
      unclear. In this study we analyzed the function of ImC isolated from tumor-free
      control and tumor-bearing mice. Only ImC isolated from tumor-bearing mice, not
      those from their control counterparts, were able to inhibit the Ag-specific
      response of CD8+ T cells. ImC obtained from tumor-bearing mice had significantly
      higher levels of reactive oxygen species (ROS) than ImC isolated from tumor-free
      animals. Accumulation of H2O2, but not superoxide or NO, was a major contributor
      to this increased pool of ROS. It appears that arginase activity played an
      important role in H2O2 accumulation in these cells. Inhibition of ROS in ImC
      completely abrogated the inhibitory effect of these cells on T cells, indicating
      that ImC generated in tumor-bearing hosts suppress the CD8+ T cell response via
      production of ROS. Interaction of ImC with Ag-specific T cells in the presence of
      specific Ags resulted in a significant increase in ROS production compared with
      control Ags. That increase was independent of IFN-gamma production by T cells,
      but was mediated by integrins CD11b, CD18, and CD29. Blocking of these integrins
      with specific Abs abrogated ROS production and ImC-mediated suppression of CD8+ T
      cell responses. This study demonstrates a new mechanism of Ag-specific T cell
      inhibition mediated by ROS produced by ImCs in cancer.

PMID- 14707073
TI  - In a transgenic model of spontaneous autoimmune diabetes, expression of a
      protective class II MHC molecule results in thymic deletion of diabetogenic CD8+
      T cells.
AB  - H-2(d) mice expressing both the influenza virus hemagglutinin (HA) as a transgene
      encoded protein on pancreatic islet beta cells (InsHA), as well as the Clone 4
      TCR specific for the dominant H-2K(d)-restricted HA epitope, can be protected
      from the development of spontaneous autoimmune diabetes by expression of the H
      2(b) haplotype. Protection occurs due to the deletion of K(d)HA-specific CD8+ T
      cells. This was unexpected as neither the presence of the InsHA transgene nor H
      2(b), individually, resulted in thymic deletion. Further analyses revealed that
      thymic deletion required both a hybrid MHC class II molecule, Ebeta(b) Ealpha(d),
      and the K(d) molecule presenting the HA epitope, which together synergize to
      effect deletion of CD4+CD8+ thymocytes. This surprising example of protection
      from autoimmunity that maps to a class II MHC molecule, yet effects an alteration
      in the CD8+ T cell repertoire, suggests that selective events in the thymus
      represent the integrated strength of signal delivered to each cell through
      recognition of a variety of different MHC-peptide ligands.

PMID- 14707074
TI  - Liver dendritic cells are less immunogenic than spleen dendritic cells because of
      differences in subtype composition.
AB  - The unique immunological properties of the liver may be due to the function of
      hepatic dendritic cells (DC). However, liver DC have not been well characterized
      because of the difficulty in isolating adequate numbers of cells for analysis.
      Using immunomagnetic bead and flow cytometric cell sorting, we compared freshly
      isolated murine liver and spleen CD11c+ DC. We found that liver DC are less
      mature, capture less Ag, and induce less T cell stimulation than spleen DC.
      Nevertheless, liver DC were able to generate high levels of IL-12 in response to
      CpG stimulation. We identified four distinct subtypes of liver DC based on the
      widely used DC subset markers CD8alpha and CD11b. Lymphoid (CD8alpha+CD11b-) and
      myeloid (CD8alpha-CD11b+) liver DC activated T cells to a similar degree as did
      their splenic DC counterparts but comprised only 20% of all liver DC. In
      contrast, the two more prevalent liver DC subsets were only weakly
      immunostimulatory. Plasmacytoid DC (B220+) accounted for 19% of liver DC, but
      only 5% of spleen DC. Our findings support the widely held notion that liver DC
      are generally weak activators of immunity, although they are capable of producing
      inflammatory cytokines, and certain subtypes potently activate T cells.

PMID- 14707075
TI  - Development of the dendritic cell system during mouse ontogeny.
AB  - Based on the view that the efficacy of the immune system is associated with the
      maturation state of the immune cells, including dendritic cells (DC), we
      investigated the development and functional potential of conventional DC and
      plasmacytoid pre-DC (p-preDC) in spleen, thymus, and lymph nodes during mouse
      development. Both CD11c+ DC and CD45RA+ p-preDC were detected in small numbers in
      the thymus as early as embryonic day 17. The ratio of DC to thymocytes reached
      adult levels by 1 wk, although the normal CD8alpha+ phenotype was not acquired
      until later. Significant, but low, numbers of DC and p-preDC were present in the
      spleen of day 1 newborn mice. The full complement of DC and p-preDC was not
      acquired until 5 wk of age. The composition of DC populations in the spleen of
      young mice differed significantly from that found in adult mice, with a much
      higher percentage (50-60% compared with 20-25%) of the CD4-CD8alpha+ DC
      population and a much lower percentage (10-20% compared with 50-60%) of the
      CD4+CD8alpha- DC population. Although the p-preDC of young mice showed a capacity
      to produce IFN-alpha comparable with that of adult mice, the conventional DC of
      young mice were less efficient than those of their adult counterparts in IL-12p70
      and IFN-gamma production and in Ag presentation. These results suggest that the
      neonatal DC system is not fully developed, and innate immunity is the dominant
      form of response. The complete DC system required for adaptive immunity in the
      mouse is not fully developed until 5 wk of age.

PMID- 14707076
TI  - IL-10 induces regulatory T cell apoptosis by up-regulation of the membrane form
      of TNF-alpha.
AB  - Numerous studies have demonstrated the role of regulatory T (Treg) cells in
      peripheral tolerance. Nevertheless, how the survival and death of Treg cells is
      controlled is largely unknown. In this study, we investigated the mechanisms
      involved in regulating the homeostasis of a subset of Ag-specific alphabetaTCR+
      CD4-CD8- double negative (DN) Treg cells. We demonstrate that DN Treg cells are
      naturally resistant to TCR cross-linking-induced apoptosis. Administration of
      exogenous IL-10 renders DN Treg cells susceptible to apoptosis, and abolishes
      their suppressive function. Furthermore, TCR cross-linking of DN Treg cells in
      the presence of IL-10 leads to the up-regulation of the membrane-bound but not
      the soluble form of TNF-alpha. Interaction of membrane bound TNF-alpha with TNFR2
      sends death signals to DN Treg cells. Blocking their interaction can reverse the
      effects of IL-10 on DN Treg cells. These results provide insights into the
      mechanisms that regulate the function and homeostasis of DN Treg cells.

PMID- 14707077
TI  - Ultraviolet radiation-induced regulatory T cells not only inhibit the induction
      but can suppress the effector phase of contact hypersensitivity.
AB  - Epicutaneous application of haptens to UV-exposed skin induces hapten-specific
      tolerance. This is mediated via regulatory T cells (Tr), as i.v. injection of T
      cells from UV-tolerized mice into naive animals renders the recipients
      unresponsive to the respective hapten. However, when UV-induced Tr are injected
      i.v. into sensitized mice, contact hypersensitivity (CHS) is not suppressed,
      suggesting that Tr inhibit the induction, but not the elicitation, of CHS and are
      inferior to T effector cells. As sensitization takes place in the lymph nodes,
      but elicitation occurs in the area of challenge, we postulated that Tr injected
      i.v. locate to the lymph nodes and not to the periphery and therefore only
      suppress the induction, not the elicitation, of CHS. Indeed, i.v. injection of Tr
      into sensitized mice did not inhibit CHS, although injection of Tr into the ears
      of sensitized mice suppressed the challenge. Inhibition was hapten specific, as
      injection of dinitrofluorobenzene (DNFB)-specific Tr into the ears of oxazolone
      (OXA)-sensitized mice did not affect challenge with OXA. However, when ears of
      OXA-sensitized mice were injected with DNFB-specific Tr and painted with DNFB
      before OXA challenge, CHS was suppressed. Inhibition correlated with the local
      expression of IL-10. Depletion studies and FACS analysis revealed that Tr express
      the lymph node-homing receptor L-selectin, but not the ligands for the skin
      homing receptors E- and P-selectin, suggesting that UV-induced Tr, although able
      to inhibit T effector cells, do not suppress the elicitation of CHS upon i.v.
      injection, because they obviously do not migrate into the skin.

PMID- 14707078
TI  - Allelic variation at the VHa locus in natural populations of rabbit (Oryctolagus
      cuniculus, L.).
AB  - The large interallelic distances between the three rabbit Ig V(H)a lineages, a1,
      a2 and a3, suggest that the persistence time of the V(H)a polymorphism could
      amount to 50 million years, which is much longer than that of MHC polymorphisms.
      Rabbit originated in the Iberian Peninsula where two subspecies coexist, one of
      which is confined to Southwestern Iberia (Oryctolagus cuniculus algirus). We
      studied the V(H) loci in the original species range to obtain a better
      understanding of the evolutionary history of this unusual polymorphism.
      Serological surveys revealed that sera from the subspecies algirus, when tested
      with V(H)a locus-specific alloantisera, showed either cross-reactivity ("a
      positive" variants) or no reaction at all ("a-blank"). Using RT-PCR, we
      determined 120 sequences of rearranged V(H) genes expressed in seven algirus
      rabbits that were typed as either a-positive or a-blank. The data show that the
      V(H) genes transcribed in a-positive rabbits are closely related to the V(H)1
      alleles of domestic rabbits. In contrast, a-blank rabbits were found to
      preferentially use V(H) genes that, although clearly related to the known V(H)a
      genes, define a new major allotypic lineage, designated a4. The a4 sequences have
      hallmark rabbit V(H)a residues together with a number of unprecedented amino acid
      changes in framework region 2 and 3. The net protein distances between the V(H)a4
      and the V(H)a1, a2, and a3 lineages were 20, 29, and 21% respectively. We
      conclude that at least four distantly related lineages of the rabbit V(H)a locus
      exist, one of which seems to be endemic in the Iberian range.

PMID- 14707079
TI  - NF-kappa B and Oct-2 synergize to activate the human 3' Igh hs4 enhancer in B
      cells.
AB  - In B cells, the Igh gene locus contains several DNase I-hypersensitive (hs) sites
      with enhancer activity. These include the 3' Igh enhancers, which are located
      downstream of the Calpha gene(s) in both mouse and human. In vivo experiments
      have implicated murine 3' enhancers, hs3B and/or hs4, in class switching and
      somatic hypermutation. We previously reported that murine hs4 was regulated by NF
      kappaB, octamer binding proteins, and Pax5 (B cell-specific activator protein).
      In this study we report that human hs4 is regulated differently. EMSAs and
      Western analysis of normal B cells before and after stimulation with anti-IgM
      plus anti-CD40 showed the same complex binding pattern formed by NF-kappaB, Oct
      1, and Oct-2 (but not by Pax5). A similar EMSA pattern was detected in mature
      human B cell lines (BL-2, Ramos, and HS-Sultan) and in diffuse large B cell
      lymphoma cell lines, although yin yang 1 protein (YY1) binding was also observed.
      We have confirmed the in vivo association of these transcription factors with hs4
      in B cells by chromatin immunoprecipitation assays. The diffuse large B cell
      lymphoma cell lines had a distinctive slow-migrating complex containing YY1
      associated with Rel-B. We have confirmed by endogenous coimmunoprecipitation an
      association of YY1 with Rel-B, but not with other NF-kappaB family members.
      Transient transfection assays showed robust hs4 enhancer activity in the mature B
      cell lines, which was dependent on synergistic interactions between NF-kappaB and
      octamer binding proteins. In addition, human hs4 enhancer activity required Oct-2
      and correlated with expression of Oct coactivator from B cells (OCA-B).

PMID- 14707080
TI  - CD23 trimers are preassociated on the cell surface even in the absence of its
      ligand, IgE.
AB  - Allergic disease is mediated by high levels of allergen-specific IgE. IgE binding
      to CD23, the low affinity receptor for IgE, results in a negative feedback signal
      leading to a decrease in IgE production. Previous studies have shown that CD23
      associates as an oligomer and that cooperative binding of at least two lectin
      domains is required for high affinity IgE binding to CD23. We have previously
      shown that cooperative binding is required for regulation of IgE production. This
      study describes the production of several mAbs that bind the stalk region of
      murine CD23. One of the Abs, 19G5, inhibited the IgE/CD23 interaction at 37
      degrees C, but not at 4 degrees C. Analysis of the binding properties of these
      Abs revealed that CD23 dissociates at high temperatures, such as 37 degrees C;
      however, the N terminus is constitutively associated, indicating partial, rather
      than complete, dissociation. A novel finding was that the stalk region,
      previously thought to mediate trimer association, was not required for
      oligomerization. These data reveal important information about the structure of
      CD23 that may be useful in modulating IgE production.

PMID- 14707081
TI  - Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and
      identification of a critical regulatory element.
AB  - Several gene families are known in which member genes are expressed in variegated
      patterns in differentiated cell types. Mechanisms responsible for imposition of a
      variegated pattern of gene expression are unknown. Members of the closely linked
      Ly49 inhibitory receptor gene family are expressed in a variegated fashion by NK
      cells. Variegated expression of these genes results in subsets of NK cells that
      differ in specificity for MHC class I molecules. To address the mechanisms
      underlying variegation, a 30-kb genomic fragment containing a single Ly49 gene
      was used to generate a panel of murine transgenic lines. The results demonstrated
      that, in almost all of the lines, the isolated Ly49A gene was expressed in a
      variegated pattern, remarkably similar in nearly all respects to the expression
      pattern of the endogenous Ly49A gene. Furthermore, the developmental timing of
      gene expression and regulation by host MHC molecules closely mirrored that of the
      endogenous Ly49A gene. Therefore, Ly49 variegation does not require competition
      in cis between different Ly49 genes, and the sequences imposing variegation are
      located proximally to Ly49 genes. Efforts to define regulatory elements of the
      Ly49A gene led to the identification of a DNase I hypersensitive site 4.5 kb
      upstream of the Ly49A gene transcription initiation site, which was shown to be
      essential for transgene expression. Highly related sequence elements were found
      upstream of other Ly49 genes, suggesting that a similar regulatory element
      controls each Ly49 gene.

PMID- 14707082
TI  - Quantitative analysis of prion-protein degradation by constitutive and immuno-20S
      proteasomes indicates differences correlated with disease susceptibility.
AB  - The main part of cytosolic protein degradation depends on the ubiquitin
      proteasome system. Proteasomes degrade their substrates into small peptide
      fragments, some of which are translocated into the endoplasmatic reticulum and
      loaded onto MHC class I molecules, which are then transported to the cell surface
      for inspection by CTL. A reliable prediction of proteasomal cleavages in a given
      protein for the identification of CTL epitopes would benefit immensely from
      additional cleavage data for the training of prediction algorithms. To increase
      the knowledge about proteasomal specificity and to gain more insight into the
      relation of proteasomal activity and susceptibility to prion disease, we digested
      sheep prion protein with human constitutive and immuno-20S proteasomes. All
      fragments generated in the digest were quantified. Our results underline the
      different cleavage specificities of constitutive and immunoproteasomes and
      provide data for the training of prediction programs for proteasomal cleavages.
      Furthermore, the kinetic analysis of proteasomal digestion of two different
      alleles of prion protein shows that even small changes in a protein sequence can
      affect the overall efficiency of proteasomal processing and thus provides more
      insight into the possible molecular background of allelic variations and the
      pathogenicity of prion proteins.

PMID- 14707083
TI  - Polymorphisms in IL-4R alpha correlate with airways hyperreactivity,
      eosinophilia, and Ym protein expression in allergic IL-13-/- mice.
AB  - The development of airways hyperreactivity in allergic IL-13(-/-) mice is
      controversial and appears to correlate with the number of times that the original
      129 x C57BL/6 founder strain has been crossed to the BALB/c background. In this
      investigation, we compared allergic responses in founder IL-13(-/-) mice crossed
      for either 5 (N5) or 10 (N10) generations to BALB/c mice. Whereas allergic N5 IL
      13(-/-) mice developed airways hyperreactivity, tissue eosinophilia, elevated
      IgE, and pulmonary expression of Ym proteins, these processes were attenuated in
      N5 IL-13(-/-) mice treated with an IL-4-neutralizing Ab, and in N10 IL-13(-/-)
      mice. These data showed that IL-4 was more effective in regulating allergic
      responses in N5 IL-13(-/-) mice than in N10 IL-13(-/-) mice. To elucidate the
      mechanism associated with these observations, we show by restriction and sequence
      analysis that N5 IL-13(-/-) mice express the C57BL/6 form of IL-4Ralpha and N10
      IL-13(-/-) mice express the BALB/c form. Despite the near identical predicted
      molecular mass of these isoforms, IL-4Ralpha from N5 IL-13(-/-) mice migrates
      with a slower electrophoretic mobility than IL-4Ralpha from N10 IL-13(-/-) mice,
      suggesting more extensive posttranslational modification of the N5 form. The
      Thre(49)Ile polymorphism in the extracellular domain of BALB/c IL-4Ralpha has
      been demonstrated to disrupt N-linked glycosylation of Asn(47) and increase the
      dissociation rate of the IL-4Ralpha/IL-4 interaction. Collectively, these data
      show that polymorphisms in IL-4Ralpha, which have been shown to affect the
      interaction with IL-4, correlate with the ability of IL-4 to regulate allergic
      responses in IL-13(-/-) mice.

PMID- 14707084
TI  - Wnt target genes identified by DNA microarrays in immature CD34+ thymocytes
      regulate proliferation and cell adhesion.
AB  - The thymus is seeded by very small numbers of progenitor cells that undergo
      massive proliferation before differentiation and rearrangement of TCR genes
      occurs. Various signals mediate proliferation and differentiation of these cells,
      including Wnt signals. Wnt signals induce the interaction of the cytoplasmic
      cofactor beta-catenin with nuclear T cell factor (TCF) transcription factors. We
      identified target genes of the Wnt/beta-catenin/TCF pathway in the most immature
      (CD4-CD8-CD34+) thymocytes using Affymetrix DNA microarrays in combination with
      three different functional assays for in vitro induction of Wnt signaling. A
      relatively small number (approximately 30) of genes changed expression, including
      several proliferation-inducing transcription factors such as c-fos and c-jun,
      protein phosphatases, and adhesion molecules, but no genes involved in
      differentiation to mature T cell stages. The adhesion molecules likely confine
      the proliferating immature thymocytes to the appropriate anatomical sites in the
      thymus. For several of these target genes, we validated that they are true
      Wnt/beta-catenin/TCF target genes using real-time quantitative PCR and reporter
      gene assays. The same core set of genes was repressed in Tcf-1-null mice,
      explaining the block in early thymocyte development in these mice. In conclusion,
      Wnt signals mediate proliferation and cell adhesion, but not differentiation of
      the immature thymic progenitor pool.

PMID- 14707085
TI  - Enhanced catalytic action of HLA-DM on the exchange of peptides lacking backbone
      hydrogen bonds between their N-terminal region and the MHC class II alpha-chain.
AB  - The class II MHC homolog HLA-DM catalyzes exchange of peptides bound to class II
      MHC proteins, and is an important component of the Ag presentation machinery. The
      mechanism of HLA-DM-mediated catalysis is largely obscure. HLA-DM catalyzes
      exchange of peptides of varying sequence, suggesting that a peptide sequence
      independent component of the MHC-peptide interaction could be involved in the
      catalytic process. Twelve conserved hydrogen bonds between the peptide backbone
      and the MHC are a prominent sequence-independent feature of the MHC-peptide
      interaction. To evaluate the relative importance of these hydrogen bonds toward
      HLA-DM action, we prepared peptide variants that lacked the ability to form one
      or more of the hydrogen bonds as a result of backbone amide N-methylation or
      truncation, and tested their ability to be exchanged by HLA-DM. We found that
      disruption of hydrogen bonds involving HLA-DR1 residues alpha51-53, a short
      extended segment at the N terminus of the alpha subunit helical region, led to
      heightened HLA-DM catalytic efficacy. We propose that those bonds are disrupted
      in the MHC conformation recognized by HLA-DM to allow structural transitions in
      that area during DM-assisted peptide release. These results suggest that peptides
      or compounds that bind MHC but cannot form these interactions would be
      preferentially edited out by HLA-DM.

PMID- 14707086
TI  - Role of commensal bacteria in development of gut-associated lymphoid tissues and
      preimmune antibody repertoire.
AB  - Intestinal bacteria are required for development of gut-associated lymphoid
      tissues (GALT), which mediate a variety of host immune functions, such as mucosal
      immunity and oral tolerance. In rabbits, the intestinal microflora are also
      required for developing the preimmune Ab repertoire by promoting somatic
      diversification of Ig genes in B cells that have migrated to GALT. We studied the
      mechanism of bacteria-induced GALT development. Bacteria were introduced into
      rabbits in which the appendix had been rendered germfree by microsurgery (we
      refer to these rabbits as germfree-appendix rabbits). We then identified specific
      members of the intestinal flora that promote GALT development. The combination of
      Bacteroides fragilis and Bacillus subtilis consistently promoted GALT development
      and led to development of the preimmune Ab repertoire, as shown by an increase in
      somatic diversification of VDJ-C micro genes in appendix B cells. Neither species
      alone consistently induced GALT development, nor did Clostridium subterminale,
      Escherichia coli, or Staphylococcus epidermidis. B. fragilis, which by itself is
      immunogenic, did not promote GALT development; hence, GALT development in rabbits
      does not appear to be the result of an Ag-specific immune response. To identify
      bacterial pathways required for GALT development, we introduced B. fragilis along
      with stress-response mutants of B. subtilis into germfree-appendix rabbits. We
      identified two Spo0A-controlled stress responses, sporulation and secretion of
      the protein YqxM, which are required for GALT development. We conclude that
      specific members of the commensal, intestinal flora drive GALT development
      through a specific subset of stress responses.

PMID- 14707087
TI  - The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is
      required for neutrophil migration and host defense.
AB  - The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of
      seven-span transmembrane receptors predominantly expressed by cells of the immune
      system. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1,
      EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized by an
      extended extracellular region with a variable number of N-terminal EGF-like
      domains. EGF-TM7 receptors bind cellular ligands as demonstrated by the
      interaction of CD97 with decay accelerating factor (CD55) and dermatan sulfate.
      Investigating the effect of newly generated mAb on the migration of neutrophilic
      granulocytes, we here report for the first time in vivo data on the function of
      CD97. In dextran sulfate sodium-induced experimental colitis, we show that homing
      of adoptively transferred neutrophils to the colon was significantly delayed when
      cells were preincubated with CD97 mAb. The consequences of this defect in
      neutrophil migration for host defense are demonstrated in a murine model of
      Streptococcus pneumoniae-induced pneumonia. Mice treated with CD97 mAb to EGF
      domain 1 (1B2) and EGF domain 3 (1C5) displayed a reduced granulocytic
      inflammatory infiltrate at 20 h after inoculation. This was associated with a
      significantly enhanced outgrowth of bacteria in the lungs at 44 h and a strongly
      diminished survival. Together, these findings indicate an essential role for CD97
      in the migration of neutrophils.

PMID- 14707088
TI  - T cytotoxic-1 CD8+ T cells are effector cells against pneumocystis in mice.
AB  - Host defenses are profoundly compromised in HIV-infected hosts due to progressive
      depletion of CD4+ T lymphocytes. A hallmark of HIV infection is Pneumocystis
      carinii (PC) pneumonia. Recently, CD8+ T cells, which are recruited to the lung
      in large numbers in response to PC infection, have been associated with some
      level of host defense as well as contributing to lung injury in BALB/c mice. In
      this study, we show that CD8+ T cells that have a T cytotoxic-1 response to PC in
      BALB/c mice, as determined by secretion of IFN-gamma, have in vitro killing
      activity against PC and effect clearance of the organism in adoptive transfer
      studies. Moreover, non-T cytotoxic-1 CD8+ T cells lacked in vitro effector
      activity and contributed to lung injury upon adoptive transfer. This dichotomous
      response in CD8+ T cell response may in part explain the clinical heterogeneity
      in the severity of PC pneumonia.

PMID- 14707089
TI  - IgE enhances parasite clearance and regulates mast cell responses in mice
      infected with Trichinella spiralis.
AB  - Trichinella spiralis infection elicits a vigorous IgE response and pronounced
      intestinal and splenic mastocytosis in mice. Since IgE both activates mast cells
      (MC) and promotes their survival in culture, we examined its role in MC responses
      and parasite elimination in T. spiralis-infected mice. During primary infection,
      wild-type but not IgE-deficient (IgE(-/-)) BALB/c mice mounted a strong IgE
      response peaking 14 days into infection. The splenic mastocytosis observed in
      BALB/c mice following infection with T. spiralis was significantly diminished in
      IgE(-/-) mice while eosinophil responses were not diminished in either the blood
      or jejunum. Similar levels of peripheral blood eosinophilia and jejunal
      mastocytosis occurred in wild-type and IgE-deficient animals. Despite the normal
      MC response in the small intestine, serum levels of mouse MC protease-1 also were
      lower in parasite-infected IgE(-/-) animals and these animals were slower to
      eliminate the adult worms from the small intestine. The number of T. spiralis
      larvae present in the skeletal muscle of IgE(-/-) mice 28 days after primary
      infection was about twice that in BALB/c controls, and the fraction of larvae
      that was necrotic was reduced in the IgE-deficient animals. An intense deposition
      of IgE in and around the muscle larvae was observed in wild-type but not in IgE
      null mice. We conclude that IgE promotes parasite expulsion from the gut
      following T. spiralis infection and participates in the response to larval stages
      of the parasite. Furthermore, our observations support a role for IgE in the
      regulation of MC homeostasis in vivo.

PMID- 14707090
TI  - The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation
      and dendritic cell-induced T cell polarization.
AB  - Dendritic cells (DC) are instrumental in orchestrating an appropriately polarized
      Th cell response to pathogens. DC exhibit considerable phenotypic and functional
      plasticity, influenced by lineage, Ag engagement, and the environment in which
      they develop and mature. In this study, we identify the human cationic peptide LL
      37, found in abundance at sites of inflammation, as a potent modifier of DC
      differentiation, bridging innate and adaptive immune responses. LL-37-derived DC
      displayed significantly up-regulated endocytic capacity, modified phagocytic
      receptor expression and function, up-regulated costimulatory molecule expression,
      enhanced secretion of Th-1 inducing cytokines, and promoted Th1 responses in
      vitro. LL-37 may be an attractive therapeutic candidate for manipulating T cell
      polarization by DC.

PMID- 14707091
TI  - The role of SIGNR1 and the beta-glucan receptor (dectin-1) in the nonopsonic
      recognition of yeast by specific macrophages.
AB  - We recently demonstrated that the beta-glucan receptor Dectin-1 (betaGR) was the
      major nonopsonic beta-glucan receptor on macrophages (Mphi) for the yeast-derived
      particle zymosan. However, on resident peritoneal Mphi, we identified an
      additional mannan-inhibitable receptor for zymosan that was distinct from the
      Mphi mannose receptor (MR). In this study, we have studied the mannose-binding
      potential of murine Mphi and identified the dendritic cell-specific ICAM-3
      grabbing nonintegrin homolog, SIGN-related 1 (SIGNR1), as a major MR on murine
      resident peritoneal Mphi. Both SIGNR1 and betaGR cooperated in the nonopsonic
      recognition of zymosan by these Mphi. When SIGNR1 was introduced into NIH3T3
      fibroblasts or RAW 264.7 Mphi, it conferred marked zymosan-binding potential on
      these cells. However, in the nonprofessional phagocytes (NIH3T3), SIGNR1 was
      found to be poorly phagocytic, suggesting that other receptors such as betaGR may
      play a more dominant role in particle internalization on professional phagocytes.
      Binding of zymosan to RAW 264.7 Mphi expressing SIGNR1 resulted in TNF-alpha
      production. Treatment of RAW 264.7 Mphi expressing SIGNR1, which express low
      levels of betaGR, with beta-glucans had little effect on binding or TNF-alpha
      production, indicating that there was no absolute requirement for betaGR in this
      process. These studies have identified SIGNR1 as a major MR for fungal and other
      pathogens present on specific subsets of Mphi.

PMID- 14707092
TI  - Mice deficient in LRG-47 display increased susceptibility to mycobacterial
      infection associated with the induction of lymphopenia.
AB  - Although IFN-gamma is essential for host control of mycobacterial infection, the
      mechanisms by which the cytokine restricts pathogen growth are only partially
      understood. LRG-47 is an IFN-inducible GTP-binding protein previously shown to be
      required for IFN-gamma-dependent host resistance to acute Listeria monocytogenes
      and Toxoplasma gondii infections. To examine the role of LRG-47 in control of
      mycobacterial infection, LRG-47(-/-) and wild-type mice were infected with
      Mycobacterium avium, and host responses were analyzed. LRG-47 protein was
      strongly induced in livers of infected wild-type animals in an IFN-gamma
      dependent manner. LRG-47(-/-) mice were unable to control bacterial replication,
      but survived the acute phase, succumbing 11-16 wk postinfection. IFN-gamma
      primed, bone marrow-derived macrophages from LRG-47(-/-) and wild-type animals
      produced equivalent levels of TNF and NO upon M. avium infection in vitro and
      developed similar intracellular bacterial loads. In addition, priming for IFN
      gamma production was observed in T cells isolated from infected LRG-47(-/-) mice.
      Importantly, however, mycobacterial granulomas in LRG-47(-/-) mice showed a
      marked lymphocyte deficiency. Further examination of these animals revealed a
      profound systemic lymphopenia and anemia triggered by infection. As LRG47(-/-) T
      lymphocytes were found to both survive and confer resistance to M. avium in
      recipient recombinase-activating gene-2(-/-) mice, the defect in cellular
      response and bacterial control in LRG-47(-/-) mice may also depend on a factor(s)
      expressed in a nonlymphocyte compartment. These findings establish a role for LRG
      47 in host control of mycobacteria and demonstrate that in the context of the IFN
      gamma response to persistent infection, LRG-47 can have downstream regulatory
      effects on lymphocyte survival.

PMID- 14707093
TI  - Staphylococcus aureus resists human defensins by production of staphylokinase, a
      novel bacterial evasion mechanism.
AB  - Alpha-defensins are peptides secreted by polymorphonuclear cells and provide
      antimicrobial protection mediated by disruption of the integrity of bacterial
      cell walls. Staphylokinase is an exoprotein produced by Staphylococcus aureus,
      which activates host plasminogen. In this study, we analyzed the impact of
      interaction between alpha-defensins and staphylokinase on staphylococcal growth.
      We observed that staphylokinase induced extracellular release of alpha-defensins
      from polymorphonuclear cells. Moreover, a direct binding between alpha-defensins
      and staphylokinase was shown to result in a complex formation. The biological
      consequence of this interaction was an almost complete inhibition of the
      bactericidal effect of alpha-defensins. Notably, staphylokinase with blocked
      plasminogen binding site still retained its ability to neutralize the
      bactericidal effect of alpha-defensins. In contrast, a single mutation of a
      staphylokinase molecule at position 74, substituting lysine for alanine, resulted
      in a 50% reduction of its alpha-defensin-neutralizing properties. The
      bactericidal properties of alpha-defensins were tested in 19 S. aureus strains in
      vitro and in a murine model of S. aureus arthritis. Staphylococcal strains
      producing staphylokinase were protected against the bactericidal effect of alpha
      defensins. When staphylokinase was added to staphylokinase-negative S. aureus
      cultures, it almost totally abrogated the effect of alpha-defensins. Finally,
      human neutrophil peptide 2 injected intra-articularly along with bacteria
      alleviated joint destruction. In this study, we report a new property of
      staphylokinase, its ability to induce secretion of defensins, to complex bind
      them and to neutralize their bactericidal effect. Staphylokinase production may
      therefore be responsible in vivo for defensin resistance during S. aureus
      infections.

PMID- 14707094
TI  - Expression of signaling lymphocytic activation molecule-associated protein
      interrupts IFN-gamma production in human tuberculosis.
AB  - Production of the Th1 cytokine IFN-gamma by T cells is considered crucial for
      immunity against Mycobacterium tuberculosis infection. We evaluated IFN-gamma
      production in tuberculosis in the context of signaling molecules known to
      regulate Th1 cytokines. Two populations of patients who have active tuberculosis
      were identified, based on their T cell responses to the bacterium. High responder
      tuberculosis patients displayed significant M. tuberculosis-dependent T cell
      proliferation and IFN-gamma production, whereas low responder tuberculosis
      patients displayed weak or no T cell responses to M. tuberculosis. The expression
      of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)
      on cells from tuberculosis patients was inversely correlated with IFN-gamma
      production in those individuals. Moreover, patients with a nonfunctional SAP gene
      displayed immune responses to M. tuberculosis similar to those of high responder
      tuberculosis patients. In contrast to SAP, T cell expression of SLAM was directly
      correlated with responsiveness to M. tuberculosis Ag. Our data suggest that
      expression of SAP interferes with Th1 responses whereas SLAM expression
      contributes to Th1 cytokine responses in tuberculosis. The study further suggests
      that SAP and SLAM might be focal points for therapeutic modulation of T cell
      cytokine responses in tuberculosis.

PMID- 14707095
TI  - The dendritic cell receptor DC-SIGN discriminates among species and life cycle
      forms of Leishmania.
AB  - Infection of dendritic cells by the human protozoal parasite Leishmania is part
      of its survival strategy. The dendritic cell receptors for Leishmania have not
      been established and might differ in their interactions among Leishmania species
      and infective stages. We present evidence that the surface C-type lectin DC-SIGN
      (CD 209) is a receptor for promastigote and amastigote infective stages from both
      visceral (Leishmania infantum) and New World cutaneous (Leishmania pifanoi)
      Leishmania species, but not for Leishmania major metacyclic promastigotes, an Old
      World species causing cutaneous leishmaniasis. Leishmania binding to DC-SIGN was
      found to be independent of lipophosphoglycan, the major glycoconjugate of the
      promastigote plasma membrane. Our findings emphasize the relevance of DC-SIGN in
      Leishmania-dendritic cell interactions, an essential link between innate and
      Leishmania-specific adaptive immune responses, and suggest that DC-SIGN might be
      a therapeutic target for both visceral and cutaneous leishmaniasis

PMID- 14707097
TI  - L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of
      Gram-positive bacteria, and activates the lectin pathway of complement.
AB  - The lectin pathway of complement is activated when a carbohydrate recognition
      complex and associated serine proteases binds to the surface of a pathogen. Three
      recognition subcomponents have been shown to form active initiation complexes:
      mannan-binding lectin (MBL), L-ficolin, and H-ficolin. The importance of MBL in
      antimicrobial host defense is well recognized, but the role of the ficolins
      remains largely undefined. This report shows that L-ficolin specifically binds to
      lipoteichoic acid (LTA), a cell wall component found in all Gram-positive
      bacteria. Immobilized LTA from Staphylococcus aureus binds L-ficolin complexes
      from sera, and these complexes initiate lectin pathway-dependent C4 turnover. C4
      activation correlates with serum L-ficolin concentration, but not with serum MBL
      levels. L-ficolin binding and corresponding levels of C4 turnover were observed
      on LTA purified from other clinically important bacteria, including Streptococcus
      pyogenes and Streptococcus agalactiae. None of the LTA preparations bound MBL, H
      ficolin, or the classical pathway recognition molecule, C1q.

PMID- 14707096
TI  - Generation of a complement-independent bactericidal IgM against a relapsing fever
      Borrelia.
AB  - The spirochetemia of relapsing fever in mice is cleared by a complement
      independent, polyclonal IgM response with reactivity to two prominent Ags of 20
      and 35 kDa. In this study, we have dissected the polyclonal IgM Ab response
      against a relapsing fever spirochete to determine the specificity of its
      complement-independent bactericidal properties. Our experimental approach
      selectively generated an IgM murine mAb from the early specific immune response
      to a variable outer membrane protein. This IgM is bactericidal in the absence of
      complement and is part of the polyclonal Ab response that mediates the clearance
      of this bacterium from the blood. Purified monoclonal IgM caused direct
      structural damage to the outer membrane of the spirochete, in the absence of
      complement, and protected both B cell- and C5-deficient mice from challenge when
      administered passively. The direct, complement-independent, bactericidal activity
      of Abs is a critical mechanism of host defense against infection.

PMID- 14707098
TI  - Identification of a novel Fc gamma RIIIa alpha-associated molecule that contains
      significant homology to porcine cathelin.
AB  - The following studies are the first to demonstrate the association of porcine
      FcgammaRIIIaalpha with a molecule that contains significant homology to the
      cathelin family of antimicrobial proteins. We performed immunoprecipitation of
      the porcine FcgammaRIIIaalpha multisubunit complex from Brij 96 lysates of
      polymorphonuclear leukocytes using the G7 mAb, which binds to FcgammaRIIIaalpha
      on the surface of porcine NK cells and phagocytes. Previous results indicate that
      the transmembrane alpha subunit of the FcgammaRIIIa complex is associated with
      the gamma subunit on the surface of porcine polymorphonuclear leukocytes and with
      several other unique proteins that surface iodinate and migrate at approximately
      15, 20, and 25 kDa when analyzed by reducing SDS-PAGE. Through characterization
      of the porcine FcgammaRIIIa complex, we identified the 15-kDa molecule as a
      unique FcgammaR-associated protein that has not been described in other systems.
      We now report an association between FcgammaRIIIaalpha and a 15-kDa molecule that
      shares homology to cathelin, a protein of undetermined function initially
      identified in porcine leukocytes. A domain with a high degree of homology to
      cathelin is found in the proregions of a family of antibiotic proteins referred
      to as cathelicidins. The results of our studies indicate the presence of a novel
      FcgammaRIIIa complex in the porcine system, and may provide new insights into the
      function of this antimicrobial protein homologue in relation to the variety of
      responses mediated through FcgammaRs.

PMID- 14707099
TI  - Different functional capacities of latent and lytic antigen-specific CD8 T cells
      in murine gammaherpesvirus infection.
AB  - Gammaherpesviruses can persist in the host in the face of an aggressive immune
      response. T cells recognize Ags expressed in both the productive and latent
      phases of the virus life cycle, however little is known about their relative
      roles in the long-term control of the infection. In this study we used the murine
      gammaherpesvirus 68 model system to investigate the relative properties of CD8 T
      cells recognizing lytic and latent viral Ags. We report that the CD8 T cell
      response to lytic phase epitopes is maximal in the lungs of infected mice at
      approximately 10 days postinfection, and is of progressively lesser magnitude in
      the mediastinal lymph nodes and spleen. In contrast, the CD8 T cell response to
      the latent M2 protein is maximal at approximately 19 days postinfection and is
      most prominent in the spleen, then progressively less in the mediastinal lymph
      node and the lung. Latent and lytic Ag-specific CD8 T cells had markedly
      different cell surface phenotypes during chronic infection, with latent Ag
      specific cells being predominantly CD62L(high) or CD43 (1B11)(high). Lytic Ag
      specific T cells had significantly lower expression of these markers.
      Importantly, latent but not lytic Ag-specific T cells could kill target cells
      rapidly in vivo during the chronic infection. These two different sets of CD8 T
      cells also responded differentially to IL-7, a cytokine involved in T cell
      homeostasis and the maintenance of T cell memory. These data have important
      implications for our understanding of immunological control during chronic
      gammaherpesvirus infections.

PMID- 14707101
TI  - Prostaglandin E2 induces degranulation-independent production of vascular
      endothelial growth factor by human mast cells.
AB  - Mast cells accumulate in large numbers at angiogenic sites, where they have been
      shown to express a number of proangiogenic factors, including vascular
      endothelial growth factor (VEGF-A). PGE(2) is known to strongly promote
      angiogenesis and is found in increased levels at sites of chronic inflammation
      and around solid tumors. The expression pattern of VEGF and the regulation of
      VEGF-A by PGE(2) were examined in cord blood-derived human mast cells (CBMC).
      CBMC expressed mRNA for five isoforms of VEGF-A and other members of the VEGF
      family (VEGF-B, VEGF-C, and VEGF-D) with strong expression of the most potent
      secretory isoforms. PGE(2) was a very strong inducer of VEGF-A(121/165)
      production by CBMC and also elevated VEGF-A mRNA expression. The amount of VEGF
      A(121/165) protein production induced by PGE(2) was 4-fold greater than that
      induced by IgE-mediated activation of CBMC. Moreover, the response to PGE(2) as
      well as to other cAMP-elevating agents such as forskolin and salbutamol was
      observed under conditions that were not associated with mast cell degranulation.
      CBMC expressed substantial levels of the EP(2) receptor, but not the EP(4)
      receptor, when examined by flow cytometry. In contrast to other reported PGE(2)
      mediated effects on mast cells, VEGF-A(121/165) production occurred via
      activation of the EP(2) receptor. These data suggest a role for human mast cells
      as a potent source of VEGF(121/165) in the absence of degranulation, and may
      provide new opportunities to regulate angiogenesis at mast cell-rich sites.

PMID- 14707100
TI  - Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent
      pathway.
AB  - T lymphocyte activation and proliferation is involved in many pathological
      processes. We have recently shown that carbon monoxide (CO), an enzymatic product
      of heme oxygenase-1 (HO-1), confers potent antiproliferative effects in airway
      and vascular smooth muscle cells. The purpose of this study was to determine
      whether CO can inhibit T lymphocyte proliferation and then to determine the
      mechanism by which CO can modulate T lymphocyte proliferation. In the presence of
      250 parts per million CO, CD3-activated T lymphocyte proliferation was,
      remarkably, inhibited by 80% when compared with controls. We observed that the
      antiproliferative effect of CO in T lymphocytes was independent of the mitogen
      activated protein kinase or cGMP signaling pathways, unlike what we demonstrated
      previously in smooth muscle cells. We demonstrate that CO inhibited caspase-3 and
      caspase-8 expression and activity, and caspase inhibition with benzyloxycarbonyl
      Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK pan-caspase inhibitor) blocked T
      lymphocyte proliferation. Furthermore, in caspase-8-deficient lymphocytes, the
      antiproliferative effect of CO was markedly attenuated, further supporting the
      involvement of caspase-8 in the antiproliferative effects of CO. CO also
      increased the protein level of p21(Cip1), and CO-mediated inhibition of caspase
      activity is partially regulated by p21(Cip1). Taken together, these data suggest
      that CO confers potent antiproliferative effects in CD3-activated T lymphocytes
      and that these antiproliferative effects in T lymphocytes are mediated by
      p21(Cip1)-dependent caspase activity, in particular caspase-8, independent of
      cGMP and mitogen-activated protein kinase signaling pathways.

PMID- 14707102
TI  - CXCR2-/- mice show enhanced susceptibility to herpetic stromal keratitis: a role
      for IL-6-induced neovascularization.
AB  - Ocular infection with HSV results in a blinding immunoinflammatory lesion known
      as herpetic stromal keratitis (HSK). Early preclinical events include
      inflammatory cell, mainly neutrophils, infiltration of the stroma, and
      neovascularization. To further evaluate the role of neutrophils in pathogenesis,
      HSV infection was compared in BALB/c and mice of the same background, but lacking
      CXCR2, the receptor for chemokines involved in neutrophil recruitment. Our
      results show clear differences in the outcome of ocular HSV infection in CXCR2-/-
      compared with control BALB/c mice. Thus, CXCR2-/- animals had minimal PMN influx
      during the first 7 days postinfection, and this correlated with a longer duration
      of virus infection in the eye compared with BALB/c mice. The CXCR2-/- mice were
      also more susceptible to HSV-induced lesions and developed HSK upon exposure to a
      dose of HSV that was minimally pathogenic to BALB/c mice. The basis for the
      greater HSK lesion susceptibility of CXCR2-/- mice was associated with an
      elevated IL-6 response, which appeared in turn to induce the angiogenic factor,
      vascular endothelial growth factor. Our results serve to further demonstrate the
      critical role of angiogenesis in the pathogenesis of ocular lesions.

PMID- 14707103
TI  - Semaphorin CD100 from activated T lymphocytes induces process extension collapse
      in oligodendrocytes and death of immature neural cells.
AB  - An inappropriate cross talk between activated T lymphocytes infiltrating the CNS
      and neural cells can sustain the onset and progression of demyelination and
      axonal degeneration in neuroinflammatory diseases. To mimic this deleterious
      cross talk, we designed an experimental paradigm consisting of transient
      cocultures of T lymphocytes chronically activated by retrovirus infection (not
      virus productive) with human multipotent neural precursors or primary
      oligodendrocytes from rat brain. We showed that activated T lymphocytes induced
      apoptotic death of multipotent neural progenitors and immature oligodendrocytes
      after a progressive collapse of their process extensions. These effects were
      reminiscent of those induced by brain semaphorin on neural cells. Blockade by
      specific Abs of soluble CD100 (sCD100)/semaphorin 4D released by activated T
      cells, or treatment with rsCD100, demonstrated that this immune semaphorin has
      the ability to collapse oligodendrocyte process extensions and to trigger neural
      cell apoptosis, most likely through receptors of the plexin family. The specific
      presence of sCD100 in the cerebrospinal fluid and of CD100-expressing T
      lymphocytes in the spinal cord of patients suffering with neuroinflammatory
      demyelination pointed to the potential pathological effect of sCD100 in the CNS.
      Thus, our results show that CD100 is a new important element in the deleterious T
      cell-neural cell cross talk during neuroinflammation and suggest its role in
      demyelination or absence of remyelination in neuroinflammatory diseases including
      multiple sclerosis and human T lymphotropic virus type 1-associated myelopathy.

PMID- 14707105
TI  - Bone marrow-derived progenitor cells are important for lung repair after
      lipopolysaccharide-induced lung injury.
AB  - Tissue repair often occurs in organs damaged by an inflammatory response.
      Inflammatory stimuli induce a rapid and massive release of inflammatory cells
      including neutrophils from the bone marrow. Recently, many studies suggested that
      bone marrow cells have the potential to differentiate into a variety of cell
      types. However, whether inflammatory stimuli induce release of bone marrow
      derived progenitor cells (BMPCs), or how much impact the suppression of BMPCs has
      on the injured organ is not clear. Here we show that LPS, a component of Gram
      negative bacterial cell walls, in the lung airways, induces a rapid mobilization
      of BMPCs into the circulation in mice. BMPCs accumulate within the inflammatory
      site and differentiate to become endothelial and epithelial cells. Moreover, the
      suppression of BMPCs by sublethal irradiation before intrapulmonary LPS leads to
      disruption of tissue structure and emphysema-like changes. Reconstitution of the
      bone marrow prevents these changes. These data suggest that BMPCs are important
      and required for lung repair after LPS-induced lung injury.

PMID- 14707104
TI  - Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by
      Toll-like receptor 2 ligands.
AB  - To analyze the role of Toll-like receptors (TLR) in the pathogenesis of
      rheumatoid arthritis, we have assessed the effects of stimulation of cultured
      synovial fibroblasts by the TLR-2 ligand bacterial peptidoglycan. By using high
      density oligonucleotide microarray analysis we identified 74 genes that were up
      regulated >2.5-fold. Fourteen CC and CXC chemokine genes were among the genes
      with the highest up-regulation. Quantitative real-time PCR analysis confirmed up
      regulation of granulocyte chemotactic protein (GCP)-2, RANTES, monocyte
      chemoattractant protein (MCP)-2, IL-8, growth-related oncogene-2, and to a lesser
      extent, macrophage-inflammatory protein 1alpha, MCP-1, EXODUS, and CXCL-16. GCP
      2, RANTES, and MCP-2 were detected in culture supernatants of synovial
      fibroblasts stimulated with peptidoglycan. Chemokine secretion induced by
      stimulation of rheumatoid arthritis synovial fibroblasts via TLR-2 was
      functionally relevant as demonstrated by chemotaxis assays. GCP-2 and MCP-2
      expression, which have not been reported previously in rheumatoid arthritis, was
      demonstrated in synovial tissue sections of patients diagnosed with rheumatoid
      arthritis but not in those with osteoarthritis. Correspondingly, synovial fluid
      levels were significantly higher in patients diagnosed with rheumatoid arthritis
      as compared with osteoarthritis. Thus, we present evidence for an induction of
      chemokine secretion by activation of synovial fibroblasts via TLR-2, possibly
      contributing to the formation of inflammatory infiltrates characteristically
      found in rheumatoid arthritis joints.

PMID- 14707106
TI  - Potential targets of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
      for multiple sclerosis therapy.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or
      statins are newly identified immunomodulators. In vivo treatment of SJL/J mice
      with lovastatin reduced the duration and clinical severity of active and passive
      experimental autoimmune encephalomyelitis (EAE), an animal model for multiple
      sclerosis. Lovastatin induced the expression of GATA3 and the phosphorylation of
      STAT6, whereas it inhibited tyrosine phosphorylation of Janus kinase 2, tyrosine
      kinase 2, and STAT4. Inhibition of the Janus kinase-STAT4 pathway by lovastatin
      modulated T0 to Th1 differentiation and reduced cytokine (IFN-gamma and TNF
      alpha) production, thus inducing Th2 cytokines (IL-4, IL-5, and IL-10). It
      inhibited T-bet (T box transcription factor) and NF-kappaB in activated T cells
      and significantly reduced infiltration of CD4- and MHC class II-positive cells to
      CNS. Further, it stabilized IL-4 production and GATA-3 expression in
      differentiated Th2 cells, whereas in differentiated Th1 cells it inhibited the
      expression of T-bet and reduced the production of IFN-gamma. Moreover, lovastatin
      exposed macrophage and BV2 (microglia) in allogeneic MLRs induced the production
      of the anti-inflammatory cytokine IL-10. These observations indicate that the
      anti-inflammatory effects of lovastatin are mediated via T cells as well as APCs,
      because it modulates the polarization patterns of naive T cell activation in an
      APC-independent system. Together, these findings reveal that lovastatin may have
      possible therapeutic value involving new targets (in both APCs and T cells) for
      the treatment of multiple sclerosis and other inflammatory diseases.

PMID- 14707107
TI  - Defective control of latent Epstein-Barr virus infection in systemic lupus
      erythematosus.
AB  - EBV infection is more common in patients with systemic lupus erythematosus (SLE)
      than in control subjects, suggesting that this virus plays an etiologic role in
      disease and/or that patients with lupus have impaired EBV-specific immune
      responses. In the current report we assessed immune responsiveness to EBV in
      patients with SLE and healthy controls, determining virus-specific T cell
      responses and EBV viral loads using whole blood recall assays, HLA-A2 tetramers,
      and real-time quantitative PCR. Patients with SLE had an approximately 40-fold
      increase in EBV viral loads compared with controls, a finding not explained by
      disease activity or immunosuppressive medications. The frequency of EBV-specific
      CD69+ CD4+ T cells producing IFN-gamma was higher in patients with SLE than in
      controls. By contrast, the frequency of EBV-specific CD69+ CD8+ T cells producing
      IFN-gamma in patients with SLE appeared lower than that in healthy controls,
      although this difference was not statistically significant. These findings
      suggest a role for CD4+ T cells in controlling, and a possible defect in CD8+ T
      cells in regulating, increased viral loads in lupus. These ideas were supported
      by correlations between viral loads and EBV-specific T cell responses in lupus
      patients. EBV viral loads were inversely correlated with the frequency of EBV
      specific CD69+ CD4+ T cells producing IFN-gamma and were positively correlated
      with the frequencies of CD69+ CD8+ T cells producing IFN-gamma and with EBV
      specific, HLA-A2 tetramer-positive CD8+ T cells. These results demonstrate that
      patients with SLE have defective control of latent EBV infection that probably
      stems from altered T cell responses against EBV.

PMID- 14707108
TI  - Periportal fibrosis in human Schistosoma mansoni infection is associated with low
      IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender.
AB  - Schistosoma mansoni infection is highly endemic in parts of Uganda, and
      periportal fibrosis is common in communities along the shore of Lake Albert. In
      this study, we have identified cellular immune responses associated with
      fibrosis. A cohort of 199 individuals aged 6-50, resident in the village for at
      least 10 years or since birth, were examined for evidence of periportal fibrosis
      by ultrasound using the Niamey protocol. Whole-blood samples were assayed for
      levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF
      alpha, IFN-gamma, IL-1beta, and RANTES) in the absence of in vitro Ag
      stimulation, and after stimulation with egg and worm Ags. A lack of Ag
      specificity allowed the number of variables in the analysis to be reduced by
      factor analysis. The resulting factor scores were then entered into a risk
      analysis using a classification tree algorithm. Children, adult males, and adult
      females had different factors associated with fibrosis. Most cases of fibrosis in
      children (eight of nine) were associated with low (<47th percentile) IL-10 factor
      scores. Adult females at lowest risk had relatively high IFN-gamma factor scores
      (>83rd percentile), whereas those at highest risk had a combination of
      intermediate (32nd to 83rd percentile) IFN-gamma and relatively high (>60th
      percentile) TNF-alpha factor scores. Adult males at lowest risk of fibrosis had
      moderate TNF-alpha factor scores (55th to 82nd percentile), and a high risk was
      associated with either high TNF-alpha factor scores (>82nd percentile), or
      intermediate TNF-alpha combined with low RANTES factor scores (<58th percentile).
      These results demonstrate that periportal fibrosis is associated with cytokine
      production profiles that vary with both age and gender.

PMID- 14707109
TI  - Functional analysis of tumor-specific Th cell responses detected in melanoma
      patients after dendritic cell-based immunotherapy.
AB  - Recently, we have demonstrated that tumor-specific CD4+ Th cell responses can be
      rapidly induced in advanced melanoma patients by vaccination with peptide-loaded
      monocyte-derived dendritic cells. Most patients showed a T cell reactivity
      against a melanoma Ag 3 (MAGE-3) peptide (MAGE-3(243-258)), which has been
      previously found to be presented by HLA-DP4 molecules. To analyze the functional
      and specificity profile of this in vivo T cell response in detail, peptide
      specific CD4+ T cell clones were established from postvaccination blood samples
      of two HLA-DP4 patients. These T cell clones recognized not only peptide-loaded
      stimulator cells but also dendritic cells loaded with a recombinant MAGE-3
      protein, demonstrating that these T cells were directed against a naturally
      processed MAGE-3 epitope. The isolated CD4+ Th cells showed a typical Th1
      cytokine profile upon stimulation. From the first patient several CD4+ T cell
      clones recognizing the antigenic peptide used for vaccination in the context of
      HLA-DP4 were obtained, whereas we have isolated from the second patient CD4+ T
      cell clones which were restricted by HLA-DQB1*0604. Analyzing a panel of
      truncated peptides revealed that the CD4+ T cell clones recognized different core
      epitopes within the original peptide used for vaccination. Importantly, a DP4
      restricted T cell clone was stimulated by dendritic cells loaded with apoptotic
      or necrotic tumor cells and even directly recognized HLA class II- and MAGE-3
      expressing tumor cells. Moreover, these T cells exhibited cytolytic activity
      involving Fas-Fas ligand interactions. These findings support that vaccination
      induced CD4+ Th cells might play an important functional role in antitumor
      immunity.

PMID- 14707110
TI  - Phagocytosis, innate immunity, and host-pathogen specificity.

PMID- 14707111
TI  - Quantitative trait analysis reveals transforming growth factor-beta2 as a
      positive regulator of early hematopoietic progenitor and stem cell function.
AB  - Elucidation of pathways involved in mouse strain-dependent variation in the
      hematopoietic stem cell (HSC) compartment may reveal novel mechanisms relevant in
      vivo. Here, we demonstrate genetically determined variation in the proliferation
      of lin-Sca1++kit+ (LSK) primitive hematopoietic progenitor cells in response to
      transforming growth factor-beta (TGF-beta) 2, the dose response of which was
      biphasic with a stimulatory effect at low concentrations. In contrast, the dose
      responses of TGF-beta1 or -beta3 were inhibitory and did not show mouse strain
      dependent variation. A quantitative trait locus (QTL) for the effect of TGF-beta2
      was identified on chromosome 4 overlapping with a QTL regulating the frequency of
      LSK cells. These overlapping QTL were corroborated by the observation that the
      frequency of LSK cells is lower in adult Tgfb2+/- mice than in wild-type
      littermates, indicating that TGF-beta2 is a genetically determined positive
      regulator LSK number in vivo. Furthermore, adult Tgfb2+/- mice have a defect in
      competitive repopulation potential that becomes more pronounced upon serial
      transplantation. In fetal TGF-beta2-deficient HSCs, a defect only appears after
      serial reconstitution. These data suggest that TGF-beta2 can act cell
      autonomously and is important for HSCs that have undergone replicative stress.
      Thus, TGF-beta2 is a novel, genetically determined positive regulator of adult
      HSCs.

PMID- 14707112
TI  - Schnurri-3 (KRC) interacts with c-Jun to regulate the IL-2 gene in T cells.
AB  - The activator protein 1 (AP-1) transcription factor is a key participant in the
      control of T cell proliferation, cytokine production, and effector function. In
      the immune system, AP-1 activity is highest in T cells, suggesting that a subset
      of T cell-specific coactivator proteins exist to selectively potentiate AP-1
      function. Here, we describe that the expression of Schnurri-3, also known as
      kappa recognition component (KRC), is induced upon T cell receptor signaling in T
      cells and functions to regulate the expression of the interleukin 2 (IL-2) gene.
      Overexpression of KRC in transformed and primary T cells leads to increased IL-2
      production, whereas dominant-negative KRC, or loss of KRC protein in KRC-null
      mice, results in diminished IL-2 production. KRC physically associates with the c
      Jun transcription factor and serves as a coactivator to augment AP-1-dependent IL
      2 gene transcription.

PMID- 14707113
TI  - Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that
      mediates recognition and elimination of human-specific pathogens.
AB  - Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are used by
      several human pathogens to anchor themselves to or invade host cells.
      Interestingly, human granulocytes express a specific isoform, CEACAM3, that
      participates together with CEACAM1 and CEACAM6 in the recognition of CEACAM
      binding microorganisms. Here we show that CEACAM3 can direct efficient, opsonin
      independent phagocytosis of CEACAM-binding Neisseria, Moraxella, and Haemophilus
      species. CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative
      versions of the small GTPase Rac. Moreover, CEACAM3 engagement triggers membrane
      recruitment and increased GTP loading of Rac that are not observed upon bacterial
      binding to CEACAM6. Internalization and Rac stimulation are also inhibited by
      compromising the integrity of an immunoreceptor tyrosine-based activation motif
      (ITAM)-like sequence in the cytoplasmic tail of CEACAM3 or by interference with
      Src family protein tyrosine kinases that phosphorylate CEACAM3. In contrast to
      interfering with CEACAM6, blockage of CEACAM3-mediated events reduces the ability
      of primary human granulocytes to internalize and eliminate CEACAM-binding
      bacteria, indicating an important role of CEACAM3 in the control of human
      specific pathogens by the innate immune system.

PMID- 14707114
TI  - Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.
AB  - Inflammation removes developing and mature lymphocytes from the bone marrow (BM)
      and induces the appearance of developing B cells in the spleen. BM granulocyte
      numbers increase after lymphocyte reductions to support a reactive
      granulocytosis. Here, we demonstrate that inflammation, acting primarily through
      tumor necrosis factor alpha (TNFalpha), mobilizes BM lymphocytes. Mobilization
      reflects a reduced CXCL12 message and protein in BM and changes to the BM
      environment that prevents homing by cells from naive donors. The effects of
      TNFalpha are potentiated by interleukin 1 beta (IL-1beta), which acts primarily
      to expand the BM granulocyte compartment. Our observations indicate that
      inflammation induces lymphocyte mobilization by suppressing CXCL12 retention
      signals in BM, which, in turn, increases the ability of IL-1beta to expand the BM
      granulocyte compartment. Consistent with this idea, lymphocyte mobilization and a
      modest expansion of BM granulocyte numbers follow injections of pertussis toxin.
      We propose that TNFalpha and IL-1beta transiently specialize the BM to support
      acute granulocytic responses and consequently promote extramedullary
      lymphopoiesis.

PMID- 14707115
TI  - Gene expression profiling of hairy cell leukemia reveals a phenotype related to
      memory B cells with altered expression of chemokine and adhesion receptors.
AB  - Hairy cell leukemia (HCL) is a chronic B cell malignancy characterized by the
      diffuse infiltration of bone marrow and spleen by cells displaying a typical
      "hairy" morphology. However, the nature of the HCL phenotype and its relationship
      to normal B cells and to other lymphoma subtypes remains unclear. Using gene
      expression profiling, we show here that HCL displays a homogeneous pattern of
      gene expression, which is clearly distinct from that of other B cell non-Hodgkin
      lymphomas. Comparison with the gene expression profiles of purified normal B cell
      subpopulations, including germinal center (GC), pre-GC (naive), and post-GC
      (memory) B cells, shows that HCL cells are more related to memory cells,
      suggesting a derivation from this B cell population. Notably, when compared with
      memory cells, HCL cells displayed a remarkable conservation in proliferation,
      apoptosis, and DNA metabolism programs, whereas they appeared significantly
      altered in the expression of genes controlling cell adhesion and response to
      chemokines. Finally, these analyses have identified several genes that are
      specifically expressed in HCL and whose expression was confirmed at the protein
      level by immunocytochemical analysis of primary HCL cases. These results have
      biological implications relevant to the pathogenesis of this malignancy as well
      as clinical implications for its diagnosis and therapy.

PMID- 14707116
TI  - BCMA is essential for the survival of long-lived bone marrow plasma cells.
AB  - Long-lived humoral immunity is manifested by the ability of bone marrow plasma
      cells (PCs) to survive for extended periods of time. Recent studies have
      underscored the importance of BLyS and APRIL as factors that can support the
      survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in
      vitro, and this survival can be further enhanced by interleukin 6. Selective up
      regulation of Mcl-1 in PCs by BLyS suggests that this alpha-apoptotic gene
      product may play an important role in PC survival. Blockade of BLyS, via
      transmembrane activator and cyclophilin ligand interactor-immunoglobulin
      treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B
      cell maturation antigen (BCMA), and lowered expression of transmembrane activator
      and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B
      cells suggests a vital role of BCMA in PC survival. Affirmation of the importance
      of BCMA in PC survival was provided by studies in BCMA-/- mice in which the
      survival of long-lived bone marrow PCs was impaired compared with wild-type
      controls. These findings offer new insights into the molecular basis for the long
      term survival of PCs.

PMID- 14707117
TI  - Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp)
      tyrosine phosphorylation is required for coupling T cell antigen receptor
      engagement to WASp effector function and T cell activation.
AB  - Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell
      activation requires its release from autoinhibitory structural constraints and
      has been attributed to WASp association with activated cdc42. Here, however, we
      show that T cell development and T cell receptor (TCR)-induced proliferation and
      actin polymerization proceed normally in WASp-/- mice expressing a WASp transgene
      lacking the cdc42 binding domain. By contrast, mutation of tyrosine residue Y291,
      identified here as the major site of TCR-induced WASp tyrosine phosphorylation,
      abrogated induction of WASp tyrosine phosphorylation and its effector activities,
      including nuclear factor of activated T cell transcriptional activity, actin
      polymerization, and immunological synapse formation. TCR-induced WASp tyrosine
      phosphorylation was also disrupted in T cells lacking Fyn, a kinase shown here to
      bind, colocalize with, and phosphorylate WASp. By contrast, WASp was tyrosine
      dephosphorylated by protein tyrosine phosphatase (PTP)-PEST, a tyrosine
      phosphatase shown here to interact with WASp via proline, serine, threonine
      phosphatase interacting protein (PSTPIP)1 binding. Although Fyn enhanced WASp
      mediated Arp2/3 activation and was required for synapse formation, PTP-PEST
      combined with PSTPIP1 inhibited WASp-driven actin polymerization and synapse
      formation. These observations identify key roles for Fyn and PTP-PEST in
      regulating WASp and imply that inducible WASp tyrosine phosphorylation can occur
      independently of cdc42 binding, but unlike the cdc42 interaction, is absolutely
      required for WASp contributions to T cell activation.

PMID- 14707118
TI  - Increased expression of interleukin 23 p19 and p40 in lesional skin of patients
      with psoriasis vulgaris.
AB  - Psoriasis is a type I-deviated disease characterized by the presence of
      interferon (IFN)-gamma and multiple IFN-related inflammatory genes in lesions.
      Because interleukin (IL)-23 is now recognized to play a role in the recruitment
      of inflammatory cells in a T helper cell (Th)1-mediated disease, we examined
      psoriasis skin lesions for production of this newly described cytokine. IL-23 is
      composed of two subunits: a unique p19 subunit and a p40 subunit shared with IL
      12. We found a reliable increase in p19 mRNA by quantitative reverse
      transcription polymerase chain reaction in lesional skin compared with
      nonlesional skin (22.3-fold increase; P = 0.001). The p40 subunit, shared by IL
      12 and IL-23, increased by 11.6-fold compared with nonlesional skin (P = 0.003),
      but the IL-12 p35 subunit was not increased in lesional skin. IL-23 was expressed
      mainly by dermal cells and increased p40 immunoreactivity was visualized in large
      dermal cells in the lesions. Cell isolation experiments from psoriatic tissue
      showed strong expression of p19 mRNA in cells expressing monocyte (CD14+ CD11c+
      CD83-) and mature dendritic cell (DC) markers (CD14- CD11c+ CD83+), whereas in
      culture, the mRNAs for p40 and p19 were strongly up-regulated in stimulated
      monocytes and monocyte-derived DCs, persisting in the latter for much longer
      periods than IL-12. Our data suggest that IL-23 is playing a more dominant role
      than IL-12 in psoriasis, a Th1 type of human inflammatory disease.

PMID- 14707119
TI  - Bone marrow allograft rejection mediated by a novel murine NK receptor, NKG2I.
AB  - Natural killer (NK) cells mediate bone marrow allograft rejection. However, the
      molecular mechanisms underlying such a rejection remain elusive. In previous
      analyses, it has been shown that NK cells recognize allogeneic target cells
      through Ly-49s and CD94/NKG2 heterodimers. Here, we describe identification and
      characterization of a novel murine NK receptor, NKG2I, belonging to the NKG2
      family. NKG2I, which was composed of 226 amino acids, showed approximately 40%
      homology to the murine NKG2D and CD94 in the C-type lectin domain. Flow
      cytometric analysis with anti-NKG2I monoclonal antibody (mAb) revealed that
      expression of NKG2I was largely confined to NK and NKT cells, but was not seen in
      T cells. Furthermore, anti-NKG2I mAb inhibited NK cell-mediated cytotoxicity,
      whereas cross-linking of NKG2I enhanced interleukin 2- and interleukin 12
      dependent interferon-gamma production. Similarly, the injection of anti-NKG2I mAb
      before the allogeneic bone marrow transfer in vivo impinged on the function of
      NKG2I, resulting in the enhanced colony formation in the spleen. NKG2I is a novel
      activating receptor mediating recognition and rejection of allogeneic target
      cells.

PMID- 14707120
TI  - Stability of homologue of Slimb F-box protein is regulated by availability of its
      substrate.
AB  - The homologue of Slimb (HOS) F-box protein is a receptor of the Skp1-Cullin1-F
      box protein (SCF(HOS)) E3 ubiquitin ligase, which mediates ubiquitination and
      degradation of beta-catenin and the inhibitor of NFkappaB, IkappaB. We found that
      HOS itself is an unstable protein that undergoes ubiquitination and degradation
      in a 26 S proteasome-dependent manner. A HOS mutant lacking the F-box that is
      deficient in binding to the core SCF components underwent ubiquitination less
      efficiently and was more stable than the wild type protein. Furthermore,
      ubiquitination and degradation of HOS was impaired in ts41 cells, in which the
      activities of Cullin-based ligases were decreased because the NEDD8 pathway was
      abrogated. Whereas HOS was directly ubiquitinated within the SCF(HOS) complex in
      vitro, the addition of phosphorylated IkappaBalpha inhibited this ubiquitination.
      Increasing cellular levels of HOS substrate (phosphorylated IkappaBalpha) by
      activating IkappaB kinase inhibited HOS ubiquitination and led to stabilization
      of HOS, indicating that interaction between HOS and its substrate might protect
      HOS from proteolysis. Taken together, our data suggest that proteolysis of HOS
      depends on its interaction with active components of the SCF complex and that HOS
      stability is regulated by a bound substrate. These findings may define a
      mechanism for maintaining activities of specific SCF complexes based on
      availability of a particular substrate.

PMID- 14707121
TI  - Ras GTPase-activating protein binds to Akt and is required for its activation.
AB  - RasGAP (Ras GTPase-activating protein) is a negative regulator as well as a
      downstream effector of Ras. To identify partners of RasGAP we used it as the bait
      in a yeast two-hybrid screen. This resulted in discovering its interaction with
      Akt. Overexpression of RasGAP or a mutant lacking the GTPase-activating domain
      (nGAP) enhanced phosphorylation and activity of Akt, which was dependent on the
      upstream integrin-linked kinase. Also, nGAP protected the cells against
      staurosporin-induced apoptosis through an Akt-dependent pathway. To determine the
      role of RasGAP in receptor-mediated activation of Akt, we used short hairpin RNA
      interference to knock out endogenous RasGAP expression. Although this procedure
      resulted in enhanced Ras activity, it inhibited Akt phosphorylation. Thus, we
      propose that Ras-GAP interacts with Akt and is necessary for its activation,
      possibly via integrin-linked kinase-mediated phosphorylation of Ser-473. The data
      suggest that this effect is independent of Ras activity.

PMID- 14707122
TI  - Mafs, Prox1, and Pax6 can regulate chicken betaB1-crystallin gene expression.
AB  - During lens fiber cell differentiation, the regulation of crystallin gene
      expression is coupled with dramatic morphological changes. Here we report that
      Mafs, Prox1, and Pax6, which are essential transcription factors for normal lens
      development, bind to three functionally important cis elements, PL1, PL2, and
      OL2, in the chicken betaB1-crystallin promoter and may cooperatively direct the
      transcription of this lens fiber cell preferred gene. Gel shift assays
      demonstrated that Mafs bind to the MARE-like sequences in the PL1 and PL2
      elements, whereas Prox1, a sequence-specific DNA-binding protein like its
      Drosophila homolog Prospero, interacts with the OL2 element. Furthermore, Pax6, a
      known repressor of the chicken betaB1-crystallin promoter, binds to all three of
      these cis elements. In transfection assays, Mafs and Prox1 activated the chicken
      betaB1-crystallin promoter; however, their transactivation ability was repressed
      when co-transfected with Pax6. Taken together with the known spatiotemporal
      expression patterns of Mafs, Prox1, and Pax6 in the developing lens, we propose
      that Pax6 occupies and represses the chicken betaB1-crystallin promoter in lens
      epithelial cells, and is displaced by Prox1 and Mafs, which activate the
      promoter, in differentiating cortical fiber cells.

PMID- 14707123
TI  - Biogenesis and topology of the transient receptor potential Ca2+ channel TRPC1.
AB  - The TRPC ion channels are candidates for the store-operated Ca(2+) entry pathway
      activated in response to depletion of intracellular Ca(2+) stores. Hydropathy
      analyses indicate that these proteins contain eight hydrophobic regions (HRs)
      that could potentially form alpha-helical membrane-spanning segments. Based on
      limited sequence similarities to other ion channels, it has been proposed that
      only six of the eight HRs actually span the membrane and that the last two
      membrane-spanning segments (HRs 6 and 8) border the ion-conducting pore of which
      HR 7 forms a part. Here we study the biogenesis and transmembrane topology of
      human TRPC1 to test this model. We have employed a truncation mutant approach
      combined with insertions of glycosylation sites into full-length TRPC1. In our
      truncation mutants, portions of the TRPC1 sequence containing one or more HRs
      were fused between the enhanced green fluorescent protein and a C-terminal
      glycosylation tag. These chimeras were transiently expressed in the human
      embryonic cell line HEK-293T. Glycosylation of the tag was used to monitor its
      location relative to the lumen of the endoplasmic reticulum and thereby HR
      orientation. Our data indicate that HRs 1, 4, and 6 cross the membrane from
      cytosol to the ER lumen, that HRs 2, 5, and 8 have the opposite orientation, and
      that HR 3 is left out of the membrane on the cytosolic side. Our results also
      show that the sequence downstream of HR 8 plays an important role in anchoring
      its C-terminal end on the cytosolic side of the membrane. This effect appears to
      prevent HR 7 from spanning the bilayer and to result in its forming a pore-like
      structure of the type previously envisioned for the TRPC channels. We speculate
      that a similar mechanism may be responsible for the formation of other ion
      channel pores.

PMID- 14707124
TI  - Sulfonylureas correct trafficking defects of ATP-sensitive potassium channels
      caused by mutations in the sulfonylurea receptor.
AB  - The pancreatic ATP-sensitive potassium (K(ATP)) channel, a complex of four
      sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits,
      regulates insulin secretion by linking metabolic changes to beta-cell membrane
      potential. Sulfonylureas inhibit K(ATP) channel activities by binding to SUR1 and
      are widely used to treat type II diabetes. We report here that sulfonylureas also
      function as chemical chaperones to rescue K(ATP) channel trafficking defects
      caused by two SUR1 mutations, A116P and V187D, identified in patients with
      congenital hyperinsulinism. Sulfonylureas markedly increased cell surface
      expression of the A116P and V187D mutants by stabilizing the mutant SUR1 proteins
      and promoting their maturation. By contrast, diazoxide, a potassium channel
      opener that also binds SUR1, had no effect on surface expression of either
      mutant. Importantly, both mutant channels rescued to the cell surface have normal
      ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either
      the A116P or the V187D mutation is capable of associating with Kir6.2 to form
      functional K(ATP) channels. Thus, sulfonylureas may be used to treat congenital
      hyperinsulinism caused by certain K(ATP) channel trafficking mutations.

PMID- 14707125
TI  - Specificity of the interaction between ubiquitin-associated domains and
      ubiquitin.
AB  - Ubiquitin-associated (UBA) domains are found in a large number of proteins with
      diverse functions involved in ubiquitination, DNA repair, and signaling pathways.
      Recent studies have shown that several UBA domain proteins interact with
      ubiquitin (Ub), specifically p62, the phosphotyrosine-independent ligand of the
      SH2 domain of p56(lck); HHR23A, a human nucleotide excision repair protein; and
      DDI1, another damage-inducible protein. NMR chemical shift mapping reveals that
      Ub binds specifically but weakly to a conserved hydrophobic epitope on HHR23A
      UBA(1) and UBA(2) and that the UBA domains bind on the hydrophobic patch on the
      surface of the five-stranded beta-sheet of Ub. Models of the UBA(1)-Ub and UBA(2)
      Ub complexes obtained from de novo docking reveal different orientations of the
      UBA domains on the Ub surface compared with those obtained by homology modeling
      with the related CUE domains, which also bind Ub. Our results suggest that UBA
      domains may interact with Ub as well as other proteins in more than one way while
      utilizing the same binding surface.

PMID- 14707126
TI  - Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell
      surface clustering.
AB  - CD147, a regulator of matrix metalloproteinase (MMP) production, showed highly
      specific association with caveolin-1 on the surface of multiple cell types. CD147
      caveolin-1 complex formation was temperature and cholesterol dependent,
      reminiscent of associations seen within caveolae/lipid rafts. However, the subset
      of caveolin-1 associated with CD147 appeared exclusively within intermediate
      density sucrose gradient fractions, rather than in the low density fractions
      containing the bulk of caveolin-1. Mutagenesis experiments revealed that CD147 Ig
      domain 2 was required for caveolin-1 association. In contrast to CD147-caveolin-1
      complexes, CD147-alpha(3) integrin association was not disrupted upon cholesterol
      depletion, occurred in high density sucrose fractions, and did not involve CD147
      Ig domain 2. Overexpression of caveolin-1 caused a specific decrease in
      clustering of cell surface CD147, as detected by "cluster specific" mAb M6/13.
      Conversely, a mutant CD147 deficient in caveolin-1 association showed enhanced
      spontaneous cell surface clustering (detected by mAb M6/13), and did not show
      decreased clustering in response to caveolin-1 overexpression. Furthermore, the
      same CD147 mutant yielded an elevated induction of MMP-1. In conclusion, caveolin
      1 associates with CD147, in a complex distinct from CD147-alpha(3) integrin
      complexes, thereby diminishing both CD147 clustering and CD147-dependent MMP-1
      inducing activity.

PMID- 14707127
TI  - Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
      activity and sialylation in distal myopathy with rimmed vacuoles.
AB  - Distal myopathy with rimmed vacuoles is an autosomal recessive muscle disease
      with preferential involvement of the tibialis anterior that spares the quadriceps
      muscles in young adulthood. In a Japanese patient with distal myopathy with
      rimmed vacuoles, we identified pathogenic mutations in the gene encoding the
      bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, which catalyzes the
      initial two steps in the biosynthesis of sialic acid. In this study, we
      demonstrated the relationship between the genetic mutations and enzymatic
      activities using an in vitro expression assay system. Furthermore, we also showed
      that the levels of sialic acid in muscle and primary cultured cells from DMRV
      patients were reduced to 60-75% of control. The reactivities to lectins were also
      variable in some myofibers, suggesting that hyposialylation and abnormal
      glycosylation in muscles may contribute to the focal accumulations of autophagic
      vacuoles, amyloid deposits, or both in patient muscle tissue. The addition of
      ManNAc and NeuAc to primary cultured cells normalized sialylation levels, thus
      demonstrating the therapeutic potential of these compounds for this disease.

PMID- 14707128
TI  - The SphS-SphR two component system is the exclusive sensor for the induction of
      gene expression in response to phosphate limitation in synechocystis.
AB  - Living organisms respond to phosphate limitation by expressing various genes
      whose products maintain an appropriate range of phosphate concentrations within
      each cell. We identified previously a two component system, which consists of
      histidine kinase SphS and its cognate response regulator SphR, which regulates
      the expression of the phoA gene for alkaline phosphatase under phosphate-limiting
      conditions in the cyanobacterium Synechocystis sp. PCC 6803. In the present
      study, we used DNA microarrays to investigate the role of SphS and SphR in the
      regulation of the genome-wide expression of genes in response to phosphate
      limitation. In wild-type cells, phosphate limitation strongly induced the
      expression of 12 genes with induction factors greater than 7. These genes were
      included in three clusters of genes, namely, the pst1 and pst2 clusters that
      encode phosphate transporters; the phoA gene and the nucH gene for the
      extracellular nuclease. Phosphate limitation strongly repressed the expression of
      only the urtA gene with induction factors below 0.2. Inactivation of either of
      SphS or SphR completely eliminated the phosphate limitation-inducible expression
      of the 12 genes and the phosphate limitation-repressible expression of the urtA
      gene. These results suggest that the SphS-SphR two component system in
      Synechocystis sp. PCC 6803 is the dominant sensory system that controls gene
      expression in response to phosphate limitation.

PMID- 14707129
TI  - Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor
      signaling.
AB  - Suppressor of cytokine signaling (SOCS) proteins are a family of Src homology 2
      containing adaptor proteins. Cytokine-inducible Src homology domain 2-containing
      protein, SOCS1, SOCS2, and SOCS3 have been implicated in the down-regulation of
      cytokine signaling. The function of SOCS4, 5, 6, and 7 are not known. KIT
      receptor signaling is regulated by protein tyrosine phosphatases and adaptor
      proteins. We previously reported that SOCS1 inhibited cell proliferation in
      response to stem cell factor (SCF). By screening the other members of SOCS
      family, we identified SOCS6 as a KIT-binding protein. Using KIT mutants and
      peptides, we demonstrated that SOCS6 bound directly to KIT tyrosine 567 in the
      juxtamembrane domain. To investigate the function of this interaction, we
      constitutively expressed SOCS6 in cell lines. Ectopic expression of SOCS6 in
      Ba/F3-KIT cell line decreased cell proliferation in response to SCF but not SCF
      induced chemotaxis. SOCS6 reduced SCF-induced activation of ERK1/2 and p38 but
      not activation of AKT or STATs in Ba/F3, murine embryonic fibroblast (MEF), or
      COS-7 cells. SOCS6 did not impair ERK and p38 activation by other stimuli. These
      results indicate that SOCS6 binds to KIT juxtamembrane region, which affects
      upstream signaling components leading to MAPK activation. Our results indicate
      that KIT signaling is regulated by several SOCS proteins and suggest a putative
      function for SOCS6 as a negative regulator of receptor tyrosine kinases.

PMID- 14707130
TI  - Specificity of the tumor necrosis factor-induced protein 6-mediated heavy chain
      transfer from inter-alpha-trypsin inhibitor to hyaluronan: implications for the
      assembly of the cumulus extracellular matrix.
AB  - The formation of the hyaluronan-rich cumulus extracellular matrix is crucial for
      female fertility and accompanied by a transesterification reaction in which the
      heavy chains (HCs) of inter-alpha-trypsin inhibitor (IalphaI)-related proteins
      are covalently transferred to hyaluronan. Tumor necrosis factor-induced protein-6
      (TNFIP6) is essential for this transfer reaction. Female mice deficient in TNFIP6
      are infertile due to the lack of a correctly formed cumulus matrix. In this
      report, we characterize the specificity of TNFIP6-mediated HC transfer from
      IalphaI to hyaluronan. Hyaluronan oligosaccharides with eight or more
      monosaccharide units are potent acceptors in the HC transfer, with longer
      oligosaccharides being somewhat more efficient. Epimerization of the N-acetyl
      glucosamine residues to N-acetyl-galactosamines (i.e. in chondroitin) still
      allows the HC transfer although at a significantly lower efficiency. Sulfation of
      the N-acetyl-galactosamines in dermatan-4-sulfate or chondroitin-6-sulfate
      prevents the HC transfer. Hyaluronan oligosaccharides disperse cumulus cells from
      expanding cumulus cell-oocyte complexes with the same size specificity as their
      HC acceptor specificity. This process is accompanied by the loss of hyaluronan
      linked HCs from the cumulus matrix and the appearance of oligosaccharide-linked
      HCs in the culture medium. Chondroitin interferes with the expansion of cumulus
      cell-oocyte complexes only when added with exogenous TNFIP6 before endogenous
      hyaluronan synthesis starts, supporting that chondroitin is a weaker HC acceptor
      than hyaluronan. Our data indicate that TNFIP6-mediated HC transfer to hyaluronan
      is a prerequisite for the correct cumulus matrix assembly and hyaluronan
      oligosaccharides and chondroitin interfere with this assembly by capturing the
      HCs of the IalphaI-related proteins.

PMID- 14707131
TI  - Characterization of growth factor-binding structures in heparin/heparan sulfate
      using an octasaccharide library.
AB  - Heparan sulfate (HS) chains interact with various growth and differentiation
      factors and morphogens, and the most interactions occur on the specific regions
      of the chains with certain monosaccharide sequences and sulfation patterns. Here
      we generated a library of octasaccharides by semienzymatic methods by using
      recombinant HS 2-O-sulfotransferase and HS 6-O-sulfotransferase, and we have made
      a systematic investigation of the specific binding structures for various heparin
      binding growth factors. An octasaccharide (Octa-I, DeltaHexA-GlcNSO(3)-(HexA
      GlcNSO(3))(3)) was prepared by partial heparitinase digestion from completely
      desulfated N-resulfated heparin. 2-O- and 6-O-sulfated Octa-I were prepared by
      enzymatically transferring one to three 2-O-sulfate groups and one to three 6-O
      sulfate groups per molecule, respectively, to Octa-I. Another octasaccharide
      containing 3 units of HexA(2SO(4))-GlcNSO(3)(6SO(4)) was prepared also from
      heparin. This octasaccharide library was subjected to affinity chromatography for
      interactions with fibroblast growth factor (FGF)-2, -4, -7, -8, -10, and -18,
      hepatocyte growth factor, bone morphogenetic protein 6, and vascular endothelial
      growth factor, respectively. Based upon differences in the affinity to those
      octasaccharides, the growth factors could be classified roughly into five groups:
      group 1 needed 2-O-sulfate but not 6-O-sulfate (FGF-2); group 2 needed 6-O
      sulfate but not 2-O-sulfate (FGF-10); group 3 had the affinity to both 2-O
      sulfate and 6-O-sulfate but preferred 2-O-sulfate (FGF-18, hepatocyte growth
      factor); group 4 required both 2-O-sulfate and 6-O-sulfate (FGF-4, FGF-7); and
      group 5 hardly bound to any octasaccharides (FGF-8, bone morphogenetic protein 6,
      and vascular endothelial growth factor). The approach using the oligosaccharide
      library may be useful to define specific structures required for binding to
      various heparin-binding proteins. Octasaccharides with the high affinity to FGF-2
      and FGF-10 had the activity to release them, respectively, from their complexes
      with HS. Thus, the library may provide new reagents to specifically regulate
      bindings of the growth factors to HS.

PMID- 14707132
TI  - Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase
      subfamily.
AB  - In examining the protein kinase components of mitogen-activated protein (MAP)
      kinase (MAPK) cascades that regulate the c-Jun N-terminal kinase (JNK) in
      Drosophila S2 cells, we previously found that distinct upstream kinases were
      involved in responses to sorbitol and lipopolysaccharide. Here we have extended
      that analysis to the possible MAPK kinase kinase kinases (MAP4Ks) in the JNK
      pathway. Fray, a putative Drosophila MAP4K, provided a major contribution to JNK
      activation by sorbitol. To explore the possible link to JNK in mammalian cells,
      we isolated and characterized OSR1 (oxidative stress-responsive 1), one of two
      human Fray homologs. OSR1 is a 58-kDa protein of 527 amino acids that is widely
      expressed in mammalian tissues and cell lines. Of potential regulators surveyed,
      endogenous OSR1 is activated only by osmotic stresses, notably sorbitol and to a
      lesser extent NaCl. However, OSR1 did not increase the activity of coexpressed
      JNK, nor did it activate three other MAPKs, p38, ERK2, and ERK5. A two-hybrid
      screen implicated another Ste20p family member, the p21-activated protein kinase
      PAK1, as an OSR1 target. OSR1 phosphorylated threonine 84 in the N-terminal
      regulatory domain of PAK1. Replacement of threonine 84 with glutamate reduced the
      activation of PAK1 by an active form of the small G protein Cdc42, suggesting
      that phosphorylation by OSR1 modulates the G protein sensitivity of PAK isoforms.

PMID- 14707133
TI  - Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the
      copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan sulfate in
      rat C6 glioma cells.
AB  - The core protein of glypican-1, a glycosylphosphatidylinositol-linked heparan
      sulfate proteoglycan, can bind Cu(II) or Zn(II) ions and undergo S-nitrosylation
      in the presence of nitric oxide. Cu(II)-to-Cu(I)-reduction supports extensive and
      permanent nitrosothiol formation, whereas Zn(II) ions appear to support a more
      limited, possibly transient one. Ascorbate induces release of nitric oxide, which
      catalyzes deaminative degradation of the heparan sulfate chains on the same core
      protein. Although free Zn(II) ions support a more limited degradation, Cu(II)
      ions support a more extensive self-pruning process. Here, we have investigated
      processing of glypican-1 in rat C6 glioma cells and the possible participation of
      the copper-containing glycosylphosphatidylinositol-linked splice variant of
      ceruloplasmin in nitrosothiol formation. Confocal microscopy demonstrated
      colocalization of glypican-1 and ceruloplasmin in endosomal compartments.
      Ascorbate induced extensive, Zn(II)-supported heparan sulfate degradation, which
      could be demonstrated using a specific zinc probe. RNA interference silencing of
      ceruloplasmin expression reduced the extent of Zn(II)-supported degradation. In
      cell-free experiments, the presence of free Zn(II) ions prevented free Cu(II) ion
      from binding to glypican-1 and precluded extensive heparan sulfate
      autodegradation. However, in the presence of Cu(II)-loaded ceruloplasmin, heparan
      sulfate in Zn(II)-loaded glypican-1 underwent extensive, ascorbate-induced
      degradation. We propose that the Cu(II)-to-Cu(I)-reduction that is required for S
      nitrosylation of glypican-1 can take place on ceruloplasmin and thereby ensure
      extensive glypican-1 processing in the presence of free Zn(II) ions.

PMID- 14707134
TI  - Repression of promoter activity by CNOT2, a subunit of the transcription
      regulatory Ccr4-not complex.
AB  - The evolutionary conserved Ccr4-Not complex controls mRNA metabolism at multiple
      levels in eukaryotic cells. Genetic analysis of not mutants in yeast identifies a
      negative role in transcription, which is dependent on core promoter structure. To
      obtain direct support for this we targeted individual core subunits of the human
      Ccr4-Not complex to promoters in transient transfections of human cells. In this
      experimental setup we found that the CNOT2 and CNOT9(hRcd1/hCaf40) subunits act
      as repressors of reporter gene activity. Interestingly, recruitment of other Ccr4
      Not subunits did not affect the reporter gene. The major repression function of
      CNOT2 is localized in a specialized protein motif, the Not-Box. This conserved
      motif is present in all CNOT2 orthologs and surprisingly also in CNOT3 orthologs.
      Repression by the Not-Box was sensitive to treatment with the histone deacetylase
      inhibitor trichostatin A. In addition, mutation of a canonical TATA-box enhanced
      repression. Our experiments show for the first time direct regulation of promoter
      activity by components of the Ccr4-Not complex.

PMID- 14707135
TI  - Gangliosides act as co-receptors for Salmonella enteritidis FliC and promote FliC
      induction of human beta-defensin-2 expression in Caco-2 cells.
AB  - Antimicrobial peptides such as defensins are crucial for host defense at mucosal
      surfaces. We reported previously that Salmonella enteritidis flagellin (FliC)
      induced human beta-defensin-2 (hBD-2) mRNA expression in Caco-2 cells via NF
      kappaB activation (Ogushi, K., Wada, A., Niidome, T., Mori, N., Oishi, K.,
      Nagatake, T., Takahashi, A., Asakura, H., Makino, S., Hojo, H., Nakahara, Y.,
      Ohsaki, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Moss, J., and Hirayama, T.
      (2001) J. Biol. Chem. 276, 30521-30526). In this study, we examined the role of
      ganglioside as co-receptors with Toll-like receptor 5 (TLR5) on FliC induction of
      hBD-2 expression in Caco-2 cells. Exogenous gangliosides suppressed FliC
      induction of hBD-2 promoter activity and binding of FliC to Caco-2 cells.
      Incorporation of exogenous ganglioside GD1a into Caco-2 cell membranes increased
      the effect of FliC on hBD-2 promoter activity. In support of a role for
      endogenous gangliosides, incubation of Caco-2 cells with dl-threo-2
      hexadecanoylamino-3-morpholino-1-phenylpropanol, a glucosylceramide synthase
      inhibitor, reduced FliC induction of hBD-2 promoter activity. GD1a-loaded CHO-K1
      expressing TLR5 cells had a higher potential for hBD-2 induction following FliC
      stimulation than GD1a-loaded CHO-K1 cells not expressing TLR5. FliC increased
      phosphorylation of mitogen-activated protein kinase, p38, and ERK1/2. Exogenous
      gangliosides GD1a, GD1b, and GT1b each suppressed FliC induction of p38 and
      ERK1/2 phosphorylation. Furthermore, FliC did not enhance luciferase activity in
      Caco-2 cells transfected with a plasmid containing a mutated activator protein 1
      binding site. These results suggest that gangliosides act as co-receptors with
      TLR5 for FliC and promote hBD-2 expression via mitogen-activated protein kinase.

PMID- 14707136
TI  - Akt is a neutral amplifier for Th cell differentiation.
AB  - Both CD28 and its relative, inducible costimulator (ICOS), have a binding motif
      for phosphatidylinositol 3-kinase (PI3K) in their cytoplasmic tail, and the
      binding of PI3K leads to activation of a serine/threonine kinase, Akt. The role
      of Akt in cytokine production and helper T (Th) cell differentiation remains
      obscure. In this study, we found that enforced expression of the constitutively
      active form (E40K) of Akt rendered CD4(+) T cells activated. Wild-type of Akt and
      E40K promoted Th1 cell differentiation in C57BL/6-derived and Th1-polarized
      BALB/c-derived CD4(+) T cells, while both promoted Th2 cell differentiation in
      BALB/c-derived and Th2-polarized C57BL/6 CD4(+) T cells. E40K also facilitated
      Th1 differentiation in CD4(+) T cells from IL-4-deficient mice with the BALB/c
      background. E40K up-regulated expression of NF-AT and c-Myb, which may be related
      to the augmentation of cytokine production by E40K. These findings indicate that
      the mechanism by which Akt augments cytokine production via CD28 and ICOS is Th
      cell type-specific and reflects the intracellular status affected by the cytokine
      milieu. We conclude that Akt is a neutral amplifier of T cell activation and Th
      differentiation.

PMID- 14707137
TI  - A novel secreted protein toxin from the insect pathogenic bacterium Xenorhabdus
      nematophila.
AB  - The bacterium Xenorhabdus nematophila is an insect pathogen that produces several
      proteins that enable it to kill insects. Screening of a cosmid library
      constructed from X. nematophila strain A24 identified a gene that encoded a novel
      protein that was toxic to insects. The 42-kDa protein encoded by the toxin gene
      was expressed and purified from a recombinant system, and was shown to kill the
      larvae of insects such as Galleria mellonella and Helicoverpa armigera when
      injected at doses of around 30-40 ng/g larvae. Sequencing and bioinformatic
      analysis suggested that the toxin was a novel protein, and that it was likely to
      be part of a genomic island involved in pathogenicity. When the native bacteria
      were grown under laboratory conditions, a soluble form of the 42-kDa toxin was
      secreted only by bacteria in the phase II state. Preliminary histological
      analysis of larvae injected with recombinant protein suggested that the toxin
      primarily acted on the midgut of the insect. Finally, some of the common
      strategies used by the bacterial pathogens of insects, animals, and plants are
      discussed.

PMID- 14707138
TI  - The death effector domain protein PEA-15 prevents nuclear entry of ERK2 by
      inhibiting required interactions.
AB  - ERK2 nuclear-cytoplasmic distribution is regulated in response to hormones and
      cellular state without the requirement for karyopherin-mediated nuclear import.
      One proposed mechanism for the movement of ERK2 into the nucleus is through a
      direct interaction between ERK2 and nucleoporins present in the nuclear pore
      complex. Previous reports have attributed regulation of ERK2 localization to
      proteins that activate or deactivate ERK2, such as the mitogen-activated protein
      (MAP) kinase kinase MEK1 and MAP kinase phosphatases. Recently, a small non
      catalytic protein, PEA-15, has also been demonstrated to promote a cytoplasmic
      ERK2 localization. We found that the MAP kinase insert in ERK2 is required for
      its interaction with PEA-15. Consistent with its recognition of the MAP kinase
      insert, PEA-15 blocked activation of ERK2 by MEK1, which also requires the MAP
      kinase insert to interact productively with ERK2. To determine how PEA-15
      influences the localization of ERK2, we used a permeabilized cell system to
      examine the effect of PEA-15 on the localization of ERK2 and mutants that have
      lost the ability to bind PEA-15. Wild type ERK2 was unable to enter the nucleus
      in the presence of an excess of PEA-15; however, ERK2 lacking the MAP kinase
      insert largely retained the ability to enter the nucleus. Binding assays
      demonstrated that PEA-15 interfered with the ability of ERK2 to bind to
      nucleoporins. These results suggest that PEA-15 sequesters ERK2 in the cytoplasm
      at least in part by interfering with its ability to interact with nucleoporins,
      presenting a potential paradigm for regulation of ERK2 localization.

PMID- 14707139
TI  - An alternative pathway of oleate beta-oxidation in Escherichia coli involving the
      hydrolysis of a dead end intermediate by a thioesterase.
AB  - The degradation of 2-trans,5-cis-tetradecadienoyl-CoA, a metabolite of oleic
      acid, by the purified complex of fatty acid oxidation from Escherichia coli was
      studied to determine how much of the metabolite is converted to 3,5-cis
      tetradecadienoyl-CoA and thereby diverted from the classical, isomerase-dependent
      pathway of oleate beta-oxidation. Approximately 10% of the 2,5-intermediate was
      converted to the 3,5-isomer. When the latter compound was allowed to accumulate,
      it strongly inhibited the flux through the main pathway. Since
      Delta(3,5),Delta(2,4)-dienoyl-CoA isomerase was not detected in E. coli cells
      grown on oleate, the 3,5-intermediate cannot be metabolized via the reductase
      dependent pathway. However, it was hydrolyzed by a thioesterase, which was most
      active with 3,5-cis-tetradecadienoyl-CoA as substrate and which was induced by
      growth of E. coli on oleate. An analysis of fatty acids present in the medium
      after growth of E. coli on oleate revealed the presence of 3,5-tetradecadienoate,
      which was not detected after cells were grown on palmitate or glucose.
      Altogether, these data prompt the conclusion that oleate is mostly degraded via
      the classical, isomerase-dependent pathway in E. coli but that a small amount of
      2-trans,5-cis-tetradecadienoyl-CoA is diverted from the pathway via conversion to
      3,5-cis-tetradecadienoyl-CoA by Delta(3),Delta(2)-enoyl-CoA isomerase. The 3,5
      intermediate, which would strongly inhibit beta-oxidation if allowed to
      accumulate, is hydrolyzed, and the resultant 3,5-tetradecadienoate is excreted
      into the growth medium. This study provides evidence for the novel function of a
      thioesterase in beta-oxidation.

PMID- 14707140
TI  - Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta
      and its association with active c-src.
AB  - Gonadotropin-releasing hormone (GnRH)-induced receptor activation has been
      demonstrated to entrain a wide variety of signaling modalities. Most signaling
      pathways are concerned with the control of serine, threonine, or tyrosine-protein
      kinases, however, in the current article we demonstrate that in both a model cell
      line and in gonadotropes, GnRH additionally mediates the activation of lipid
      directed kinases. We have shown that there is a functional connection between
      protein-tyrosine kinase modulation and lipid kinase activation. In HEK293 cells
      stably expressing the Type I mammalian GnRH receptor, we employed a proteomic
      approach to identify novel protein binding partners for GnRH-activated c-Src.
      Using matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry we identified a GnRH-induced association between c-Src and the lipid
      kinase, diacylglycerol kinase-zeta (DGK-zeta). Using reciprocal co
      immunoprecipitation we show that there is a significant elevation of the
      association between catalytically active c-Src with DGK-zeta in both HEK293 cells
      and murine gonadotrope LbetaT2 cells. Employing lipid kinase assays we have shown
      that the catalytic activity of DGK-zeta is significantly heightened in both
      HEK293 and LbetaT2 cells by GnRH. In addition, we demonstrate that the activation
      of DGK-zeta exerts a functional role in the murine gonadotrope LbetaT2 cell line.
      Elevated expression of DGK-zeta resulted in a shortening of the time scale of ERK
      activation in these cells suggesting a potential role of endogenous DGK-zeta in
      controlling the induction of LHbeta transcription by ERK1/2.

PMID- 14707141
TI  - hGTSE-1 expression stimulates cytoplasmic localization of p53.
AB  - hGTSE-1 (human G(2) and S phase-expressed-1) is a cell cycle-regulated protein
      mainly localized in the cytoplasm and apparently associated with the
      microtubules. hGTSE-1 is able to down-regulate levels and activity of the p53
      tumor suppressor protein: it binds the C-terminal region of p53 and represses its
      ability to induce apoptosis after DNA damage. Here we report that, after DNA
      damage, hGTSE-1 becomes stabilized in a p53-independent way and accumulated in
      the nucleus. Further characterization of hGTSE-1 localization revealed increased
      nuclear staining in unstressed cells after treatment with the nuclear export
      inhibitor leptomycin B, or when a nuclear export signal (NES) located in its C
      terminal region was mutated. Finally, we provide evidence that hGTSE-1 ectopic
      expression, in addition to p53 protein levels down-regulation, is able to enhance
      cytoplasmic localization of p53. Interestingly, NES-mutated hGTSE-1 accumulates
      in the nucleus, binds p53 but looses its ability to enhance cytoplasmic
      redistribution of p53 and to regulate p53 protein levels. Similarly, when wild
      type hGTSE-1 functions on p53 were analyzed in cells lacking Mdm2, it failed in
      regulating both p53 localization and protein levels, thus indicating that hGTSE-1
      requires an intact NES and functional Mdm2 for the regulation of p53. Our results
      provide new insights into the mechanism of hGTSE-1 function, whereby its
      characterized nucleo-cytoplasmic shuttling ability is required to regulate p53.

PMID- 14707142
TI  - Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor
      cell surface stability.
AB  - GABA(B) receptors are heterodimeric G protein-coupled receptors that mediate slow
      synaptic inhibition in the central nervous system. The dynamic control of the
      cell surface stability of GABA(B) receptors is likely to be of fundamental
      importance in the modulation of receptor signaling. Presently, however, this
      process is poorly understood. Here we demonstrate that GABA(B) receptors are
      remarkably stable at the plasma membrane showing little basal endocytosis in
      cultured cortical and hippocampal neurons. In addition, we show that exposure to
      baclofen, a well characterized GABA(B) receptor agonist, fails to enhance GABA(B)
      receptor endocytosis. Lack of receptor internalization in neurons correlates with
      an absence of agonist-induced phosphorylation and lack of arrestin recruitment in
      heterologous systems. We also demonstrate that chronic exposure to baclofen
      selectively promotes endocytosis-independent GABA(B) receptor degradation. The
      effect of baclofen can be attenuated by activation of cAMP-dependent protein
      kinase or co-stimulation of beta-adrenergic receptors. Furthermore, we show that
      increased degradation rates are correlated with reduced receptor phosphorylation
      at serine 892 in GABA(B)R2. Our results support a model in which GABA(B)R2
      phosphorylation specifically stabilizes surface GABA(B) receptors in neurons. We
      propose that signaling pathways that regulate cAMP levels in neurons may have
      profound effects on the tonic synaptic inhibition by modulating the availability
      of GABA(B) receptors.

PMID- 14707143
TI  - Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca2+
      signaling.
AB  - Three subtypes of inositol 1,4,5-trisphosphate receptor (IP(3)R1, IP(3)R2, and
      IP(3)R3) Ca(2+) release channel share basic properties but differ in terms of
      regulation. To what extent they contribute to complex Ca(2+) signaling, such as
      Ca(2+) oscillations, remains largely unknown. Here we show that HeLa cells
      express comparable amounts of IP(3)R1 and IP(3)R3, but knockdown by RNA
      interference of each subtype results in dramatically distinct Ca(2+) signaling
      patterns. Knockdown of IP(3)R1 significantly decreases total Ca(2+) signals and
      terminates Ca(2+) oscillations. Conversely, knockdown of IP(3)R3 leads to more
      robust and long lasting Ca(2+) oscillations than in controls. Effects of IP(3)R3
      knockdown are surprisingly similar in COS-7 cells that predominantly (>90% of
      total IP(3)R) express IP(3)R3, suggesting that IP(3)R3 functions as an anti
      Ca(2+)-oscillatory unit without contributing to peak amplitude of Ca(2+) signals,
      irrespective of its relative expression level. Therefore, differential expression
      of the IP(3)R subtype is critical for various forms of Ca(2+) signaling, and,
      particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca(2+)
      oscillations.

PMID- 14707144
TI  - A stepwise dissection of the intracellular fate of cationic cell-penetrating
      peptides.
AB  - The role of endosomal acidification and retrograde transport for the uptake of
      the highly basic cell-penetrating peptides penetratin, Tat, and oligoarginine was
      investigated. The effect of a panel of drugs that interfere with discrete steps
      of endocytosis or Golgi-mediated transport on uptake and cellular distribution of
      fluorescein-labeled peptide analogues was probed by confocal microscopy, flow
      cytometry, and fluorescence spectroscopy of whole cell lysates. The analyses were
      carried out in MC57 fibrosarcoma cells and in HeLa cells. While MC57 fibrosarcoma
      cells showed some vesicular fluorescence and a pronounced cytoplasmic
      fluorescence, in HeLa cells little cytoplasmic fluorescence was observed. In MC57
      cells the inhibitors of endosomal acidification chloroquine and bafilomycin A1
      abolished the release of the peptides into the cytoplasm. Release into the
      cytosol preserved endosomal integrity. In addition, cellular uptake of the
      peptides was inhibited by brefeldin A, a compound interfering with trafficking in
      the trans-Golgi network. In contrast, nordihydroguaiaretic acid, a drug that
      stimulates the rapid retrograde movement of both Golgi stacks and trans-Golgi
      network to the endoplasmic reticulum, promoted a cytoplasmic localization of Tat
      peptides in peptide-pulsed HeLa cells. The effects of these drugs on trafficking
      shared characteristics with those reported for the trafficking of plant and
      bacterial toxins, such as cholera toxin, which reach the cytoplasm by means of
      retrograde transport. A sequence comparison revealed a common stretch of 8-10
      amino acids with high sequence homology to the Tat peptide. The structural and
      functional data therefore strongly suggest a common mechanism of import for
      cationic cell-penetrating peptides and the toxins.

PMID- 14707145
TI  - Factors that influence selection of coding resumption sites in translational
      bypassing: minimal conventional peptidyl-tRNA:mRNA pairing can suffice.
AB  - This study investigates bypassing initiated from codons immediately 5' of a stop
      codon. The mRNA slips and is scanned by the peptidyl-tRNA for a suitable landing
      site, and standard decoding resumes at the next 3' codon. This work shows that
      landing sites with potentially strong base pairing between the peptidyl-tRNA
      anticodon and mRNA are preferred, but sites with little or no potential for
      Watson-Crick or wobble base pairing can also be utilized. These results have
      implications for re-pairing in ribosomal frameshifting. Shine-Dalgarno sequences
      in the mRNA can alter the distribution of landing sites observed. The
      bacteriophage T4 gene 60 nascent peptide, known to influence take-off in its
      native context, imposes stringent P-site pairing requirements, thereby limiting
      the number of suitable landing sites.

PMID- 14707146
TI  - Identification and characterization of a glycosaminoglycan recognition element of
      the C chemokine lymphotactin.
AB  - Chemokine-mediated recruitment of leukocytes in vivo depends on interactions with
      cell surface glycosaminoglycans. Lymphotactin, the unique member of the "C"
      chemokine subclass, is a highly basic protein that binds heparin, a
      glycosaminoglycan, with high affinity (approximately 10 nm). We detected
      lymphotactin-heparin binding by NMR and mapped this interaction to a narrow
      surface that wraps around the protein. Substitutions in and around this binding
      site and surface plasmon resonance analysis of heparin binding affinity
      identified two arginine residues of lymphotactin as critical for
      glycosaminoglycan binding. Both arginine mutant proteins and the combined double
      mutant had dramatically diminished in vivo activity in a leukocyte recruitment
      assay, suggesting that the lymphotactin-glycosaminoglycan interactions detected
      in vitro are important for the function of this chemokine. Our results
      demonstrate that like other chemokines, lymphotactin utilizes highly specific
      glycosaminoglycan-binding sites that represent potential targets for drug
      development.

PMID- 14707147
TI  - HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin.
AB  - Induction of heat shock protein (HSP) gene expression by stress is initiated by
      binding of HSF1 to HSP gene promoters to increase their transcription. The
      cytoprotective functions of these HSPs are essential for cell survival, and thus
      it is critical that inducible HSP gene expression be executed rapidly and
      efficiently. Here we report an interaction between heat shock factor 1 (HSF1) and
      symplekin, a protein known to form a complex with the polyadenylation factors
      CstF and CPSF. HSF1-symplekin complexes are detected only after stress treatment,
      and these two proteins co-localize in punctate nuclear structures in stressed
      cells. HSF1 also complexes in a stress-induced manner with the 3' processing
      factor CstF-64. Interfering with HSF1-symplekin interaction by overexpressing a
      non-DNA-binding mutant HSF1 protein significantly decreases Hsp70 mRNA
      polyadenylation in stressed cells, supporting the functional role for HSF1 in
      promoting 3' processing of this transcript. Importantly, this was also found to
      result in a significant loss of Hsp70 protein induction and increased cell death
      in response to stress exposure. These results indicate that the HSF1-symplekin
      interaction functions as a mechanism for recruiting polyadenylation factors to
      HSP genes to enhance the efficiency/kinetics of production of mature Hsp mRNA
      transcripts to achieve the critical cellular need for rapid HSP expression after
      stress. Thus, HSF1 regulates HSP gene expression at not one but two different
      steps of the expression pathway, functioning both as a transcription factor and a
      polyadenylation stimulatory factor.

PMID- 14707148
TI  - Rheology of airway smooth muscle cells is associated with cytoskeletal
      contractile stress.
AB  - Recently reported data from mechanical measurements of cultured airway smooth
      muscle cells show that stiffness of the cytoskeletal matrix is determined by the
      extent of static contractile stress borne by the cytoskeleton (Wang N, Tolic
      Norrelykke IM, Chen J, Mijailovich SM, Butler JP, Fredberg JJ, and Stamenovic D.
      Am J Physiol Cell Physiol 282, C606-C616, 2002). On the other hand, rheological
      measurements on these cells show that cytoskeletal stiffness changes with
      frequency of imposed mechanical loading according to a power law (Fabry B, Maksym
      GN, Butler JP, Glogauer M, Navajas DF, and Fredberg JJ. Phys Rev Lett 87: 148102,
      2001). In this study, we examine the possibility that these two empirical
      observations might be interrelated. We combine previously reported data for
      contractile stress of human airway smooth muscle cells with new data describing
      rheological properties of these cells and derive quantitative, mathematically
      tractable, and experimentally verifiable empirical relationships between
      contractile stress and indexes of cell rheology. These findings reveal an
      intriguing role of the contractile stress: although it maintains structural
      stability of the cell under applied mechanical loads, it may also regulate
      rheological properties of the cytoskeleton, which are essential for other cell
      functions.

PMID- 14707149
TI  - Resistance training enhances components of the insulin signaling cascade in
      normal and high-fat-fed rodent skeletal muscle.
AB  - Our laboratory recently reported that chronic resistance training (RT) improved
      insulin-stimulated glucose transport in normal rodent skeletal muscle, owing, in
      part, to increased GLUT-4 protein concentration (Yaspelkis BB III, Singh MK,
      Trevino B, Krisan AD, and Collins DE. Acta Physiol Scand 175: 315-323, 2002).
      However, it remained to be determined whether these improvements resulted from
      alterations in the insulin signaling cascade as well. In addition, the
      possibility existed that RT might improve skeletal muscle insulin resistance.
      Thirty-two male Sprague-Dawley rats were assigned to four groups: control diet
      (Con)-sedentary (Sed); Con-RT; high-fat diet (HF)-Sed; and HF-RT. Animals
      consumed their respective diets for 9 wk; then RT animals performed 12 wk of
      training (3 sets, 10 repetitions at 75% one-repetition maximum, 3x/wk). Animals
      remained on their dietary treatments over the 12-wk period. After the training
      period, animals were subjected to hindlimb perfusions. Insulin-stimulated insulin
      receptor substrate-1-associated phosphatidylinositol-3 kinase activity was
      enhanced in the red gastrocnemius and quadriceps of Con-RT and HF-RT animals.
      Atypical PKC-zeta/lambda and Akt activities were reduced in HF-Sed and normalized
      in HF-RT animals. Resistance training increased GLUT-4 protein concentration in
      red gastrocnemius and quadriceps of Con-RT and HF-RT animals. No differences were
      observed in total protein concentrations of insulin receptor substrate-1, Akt,
      atypical PKC-zeta/lambda, or phosphorylation of Akt. Collectively, these findings
      suggest that resistance training increases insulin-stimulated carbohydrate
      metabolism in normal skeletal muscle and reverses high-fat diet-induced skeletal
      muscle insulin resistance by altering components of both the insulin signaling
      cascade and glucose transporter effector system.

PMID- 14707150
TI  - Rest insertion combined with high-frequency loading enhances osteogenesis.
AB  - Mechanical loading can significantly affect skeletal adaptation. High-frequency
      loading can be a potent osteogenic stimulus. Additionally, insertion of rest
      periods between consecutive loading bouts can be a potent osteogenic stimulus.
      Thus we investigated whether the insertion of rest-periods between short-term
      high-frequency loading bouts would augment adaptation in the mature murine
      skeleton. Right tibiae of skeletally mature (16 wk) female C57BL/6 mice were
      loaded in cantilever bending at peak of 800 microepsilon, 30 Hz, 5 days/wk for 3
      wk. Left tibiae were the contralateral control condition. Mice were randomly
      assigned into one of two groups: continuous high-frequency (CT) stimulation for
      100 s (n = 9), or 1-s pulses of high-frequency stimuli followed by 10 s of rest
      (RI) for 100 s (n = 9). Calcein labels were administered on days 1 and 21; label
      incorporation was used to histomorphometrically assess periosteal and endosteal
      indexes of adaptation. Periosteal surface referent bone formation rate (pBFR/BS)
      was significantly enhanced in CT (>88%) and RI (>126%) loaded tibiae, relative to
      control tibiae. Furthermore, RI tibiae had significantly greater pBFR/BS,
      relative to CT tibiae (>72%). The endosteal surface was not as sensitive to
      mechanical loading as the periosteal surface. Thus short-term high-frequency
      loading significantly elevated pBFR/BS, relative to control tibiae. Furthermore,
      despite the 10-fold reduction in cycle number, the insertion of rest periods
      between bouts of high-frequency stimuli significantly augmented pBFR/BS, relative
      to tibiae loaded continually. Optimization of osteogenesis in response to
      mechanical loading may underpin the development of nonpharmacological regiments
      designed to increase bone strength in individuals with compromised bone
      structures.

PMID- 14707151
TI  - Salt intake, endothelial cell signaling, and progression of kidney disease.
AB  - It has been known for decades that increased dietary intake of salt (NaCl)
      shortens the life span of rats in a dose-dependent fashion. This review focuses
      specifically on the recently described biological effect and consequences of
      increased salt ingestion on the endothelium through a mechanism that is
      independent of blood pressure. Changes in salt intake are recognized by
      endothelial cells in the vascular tree and glomeruli through a physical process
      that promotes a series of signaling events involved in transcriptional regulation
      of genes that include transforming growth factor-beta1 (TGF-beta1) and the
      endothelial isoform of nitric oxide synthase (NOS3). A balance is struck between
      TGF-beta1 and NOS3 as salt intake varies and creates a negative feedback loop,
      because TGF-beta1 increased expression of NOS3 and NO inhibited production of TGF
      beta1 in healthy rats. Changes in this feedback system have been observed in salt
      sensitive hypertension and appear to impact end-organ damage, particularly the
      kidney. The data support an important benefit to reduction of salt intake in the
      setting of chronic kidney disease.

PMID- 14707152
TI  - Calcium channel blocker azelnidipine enhances vascular protective effects of AT1
      receptor blocker olmesartan.
AB  - The present studies were undertaken to investigate the potential effect of a
      calcium channel blocker (CCB) to enhance the inhibitory effect of an angiotensin
      (Ang) II type 1 (AT1) receptor blocker (ARB) on vascular injury and the cellular
      mechanism of the effect of CCB on vascular remodeling. In polyethylene cuff
      induced vascular injury of the mouse femoral artery, proliferation of vascular
      smooth muscle cells (VSMCs) and neointimal formation associated with activation
      of extracellular signal-regulated kinase (ERK), and tyrosine-phosphorylation of
      signal transducer and activator of transcription (STAT)1 and STAT3, inflammatory
      response assessed by monocyte chemoattractant protein-1 and tumor necrosis factor
      alpha expression, as well as oxidative stress such as expression of NADH/NADPH
      oxidase p22(phox) subunit and superoxide production, were less in AT1a receptor
      null mice. Administration of nonhypotensive doses of a CCB, azelnidipine (0.5 or
      1 mg/kg per day) attenuated these parameters in wild-type and AT1a receptor null
      mice. Coadministration of lower doses of an ARB, olmesartan (0.5 mg/kg per day),
      and azelnidipine (0.1 mg/kg per day), which did not affect vascular remodeling,
      significantly inhibited these parameters in wild-type mice. Moreover, the
      effective dose of azelnidipine (1 mg/kg per day) exaggerated the inhibitory
      action of olmesartan at effective doses of 1 or 3 mg/kg per day on VSMC
      proliferation in the injured arteries. These results suggest that azelnidipine
      could inhibit vascular injury at least partly independent of the inhibition of
      AT1 receptor activation and that azelnidipine could exaggerate the vascular
      protective effects of olmesartan, suggesting clinical possibility that the
      combination of CCB and ARB could be more effective in the treatment of vascular
      diseases.

PMID- 14707153
TI  - The sympathetic nervous system and hypertension: recent developments.

PMID- 14707154
TI  - Effect of dietary sodium intake on blood lipids: results from the DASH-sodium
      trial.
AB  - We evaluated the effect on serum lipids of sodium intake in 2 diets. Participants
      were randomly assigned to a typical American control diet or the Dietary
      Approaches to Stop Hypertension (DASH) diet, each prepared with 3 levels of
      sodium (targeted at 50, 100, and 150 mmol/d per 2100 kcal). The DASH diet is
      increased in fruits, vegetables, and low-fat dairy products and is reduced in
      saturated and total fat. Within assigned diet, participants ate each sodium level
      for 30 days. The order of sodium intake was random. Participants were 390 adults,
      age 22 years or older, with blood pressure of 120 to 159 mm Hg systolic and 80 to
      95 mm Hg diastolic. Serum lipids were measured at baseline and at the end of each
      sodium period. Within each diet, sodium intake did not significantly affect serum
      total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides. On the
      control diet, the ratio of total cholesterol-to-HDL cholesterol increased by 2%
      from 4.53 on higher sodium to 4.63 on lower sodium intake (P=0.04). On the DASH
      diet, sodium intake did not affect this ratio. There was no dose-response of
      sodium intake on serum lipids or the cholesterol ratio in either diet. At each
      sodium level, total cholesterol, LDL cholesterol, and HDL cholesterol were lower
      on the DASH diet versus the typical American diet. There were no significant
      interactions between the effects of sodium and the DASH diet on serum lipids. In
      conclusion, changes in dietary sodium intake over the range of 50 to 150 mmol/d
      did not affect blood lipid concentrations.

PMID- 14707155
TI  - Reduced endothelial NO-cGMP-mediated vascular relaxation and hypertension in IL-6
      infused pregnant rats.
AB  - Placental ischemia during pregnancy is associated with increased plasma cytokines
      such as interleukin-6 (IL-6), which may contribute to increased vascular
      resistance and hypertension of pregnancy. We tested the hypothesis that an
      increase in plasma IL-6 during pregnancy is associated with impaired endothelium
      dependent relaxation, enhanced vascular contraction, and hypertension. Systolic
      blood pressure was measured in virgin and pregnant Sprague-Dawley rats non
      treated or infused with IL-6 (200 ng/kg per day for 5 days). Isometric
      contraction was measured in isolated aortic strips, and endothelial nitric oxide
      (NO) synthase (eNOS) was measured in aortic homogenate using Western blots. Blood
      pressure was greater in IL-6-infused (146+/-3) than in control pregnant rats
      (117+/-2 mm Hg). In endothelium-intact vascular strips, phenylephrine (Phe)
      caused greater increase in active stress in IL-6-infused (maximum: 10.6+/-0.6)
      than in control pregnant rats (maximum: 4.1+/-0.3x10(4) N/m2). Acetylcholine
      (ACh)-induced relaxation of Phe contraction and vascular eNOS protein and
      nitrite/nitrate production were less in IL-6-infused than in control pregnant
      rats. N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), inhibitor of NOS, or
      1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (10(-5) mol/L), inhibitor of cGMP
      production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe
      induced stress in control but not IL-6-infused pregnant rats. Endothelium removal
      enhanced Phe-induced stress in control but not in IL-6-infused pregnant rats. The
      blood pressure and vascular Phe-induced contraction, ACh relaxation, and eNOS
      protein were not different between control and IL-6-infused virgin rats. Thus, an
      endothelium-dependent NO-cGMP-mediated relaxation pathway is inhibited in
      systemic vessels of pregnant rats infused with IL-6. The results support a role
      for IL-6 as a possible mediator of the increased vascular resistance during
      hypertension of pregnancy.

PMID- 14707156
TI  - Tempol lowers blood pressure and sympathetic nerve activity but not vascular O2-
      in DOCA-salt rats.
AB  - This study tested the hypothesis that depressor responses caused by tempol are
      not associated with reductions in vascular O2- levels in urethane-anesthetized
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We compared the
      effects of intravenous (IV) administration of tempol, apocynin, superoxide
      dismutase-polyethylene glycol (PEG-SOD), and SOD on mean arterial blood pressure
      (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). In DOCA-salt
      rats, tempol (30 to 300 micromol/kg) dose-dependently decreased RSNA, MAP, and
      HR. Tempol (300 micromol/kg) decreased MAP from 140+/-5 to 83+/-4 mm Hg (P<0.05).
      HR decreased from 435+/-15 to 390+/-12 bpm (P<0.05). RSNA was reduced by 54%+/-6%
      from baseline. However, in the same rats, tempol did not reduce dihydroethidium
      induced fluorescent signals in the aorta and vena cava. Apocynin (200
      micromol/kg) did not lower MAP (142+/-5 mm Hg versus 140+/-6 mm Hg) or HR (428+/
      15 bpm versus 420+/-13 bpm) and apocynin did not potentiate depressor responses
      caused by tempol. PEG-SOD (10 000 U/kg, bolus or 5000 U/kg bolus followed by a 30
      minutes infusion of 500 U/kg/min) or SOD (25 000 U/kg, bolus or 10 000 U/kg bolus
      followed by a 30-minutes infusion of 1000 U/kg per minute) did not alter MAP or
      HR. It is concluded that depressor responses and decreases in HR and RSNA caused
      by acute tempol treatment are caused by direct sympathetic nerve activity
      inhibition that is not accompanied by SOD-mimetic action in the aorta or vena
      cava.

PMID- 14707157
TI  - 20-HETE and circulating insulin in essential hypertension with obesity.
AB  - Analogous to observations in Dahl salt-sensitive (SS) rats, we have shown that 20
      hydroxyeicosatetraenoic acid (20-HETE) is involved in the pathogenesis of SS
      essential hypertension. A strong negative correlation between urine 20-HETE and
      body mass index (BMI) remains unexplained. We measured BP, urine sodium (UNaV),
      and 20-HETE in obese hypertensive subjects during a 24-hour salt load (160 mmol
      NaCl diet+2 L intravenous saline). We classified them into insulin-resistant (IR)
      (n=14) and insulin-sensitive (IS) (n=12), with the average insulin sensitivity
      index (SI=22.5x[fasting glucose x insulin](-1)) of 3 days (cutoff for IR, SI
      <0.161 mL x L/microU x mmol). IR were older (50+/-1 versus 44+/-2, P<0.03), more
      obese (BMI 38.2+/-1.4 versus 32.0+/-1.5 kg/m2, P<0.01), and had higher insulin
      (39.2+/-2.3 versus 22.0+/-1.1 microU/mL, P<0.0001) and lower SI (0.084+/-0.009
      versus 0.222+/-0.013, P<0.0001) than IS. Blood pressure, UNaV, and sodium balance
      did not differ between groups. SI correlated negatively with age (r=-0.39,
      P<0.05) and BMI (r=-0.53, P<0.01). Urine 20-HETE was less in IR than in IS when
      normalized by serum insulin (0.91+/-0.25 versus 2.24+/-0.46 microg. 24 hours(
      1)/microU x mL(-1), P<0.02), but not if uncorrected. Urinary 20-HETE excretion
      correlated negatively with insulin (r=-0.40, P<0.04), whereas the relationship
      between 20-HETE and SI was not statistically significant. Our data suggest that
      increased circulating insulin, not the state of insulin resistance, suppresses
      urine 20-HETE excretion in obese hypertensive subjects. Findings in experimental
      models suggest that an inhibitory effect of insulin on cytochrome P4504A, rather
      than effects of insulin on membrane-bound arachidonic acid or on its release to
      the cytosol, may explain our observation.

PMID- 14707158
TI  - Persistent remodeling of resistance arteries in type 2 diabetic patients on
      antihypertensive treatment.
AB  - We hypothesized that resistance arteries from diabetic patients with controlled
      hypertension have less remodeling than vessels from untreated hypertensive
      subjects. Eight normotensive subjects (aged 44+/-3 years, 3 men; values are
      mean+/-SEM), 19 untreated hypertensive subjects (46+/-2 years, 9 men), and 23
      hypertensive subjects with type 2 diabetes mellitus under antihypertensive
      treatment (58+/-1 years, 15 men) were studied. Resistance arteries dissected from
      gluteal subcutaneous tissue were assessed on a pressurized myograph. Most
      diabetic patients (70%) were being treated with angiotensin-converting enzyme
      inhibitors. Although systolic blood pressure was still above the normotensive
      range in these patients (144+/-2 versus 150+/-3 mm Hg in hypertensive and 114+/-4
      mm Hg in normotensive subjects), diastolic blood pressure was well controlled
      (83+/-2 mm Hg) and significantly lower compared with that in untreated
      hypertensives (100+/-1 mm Hg; P<0.001) but higher than in normotensives (76+/-3
      mm Hg; P<0.05). Thus, pulse pressure was higher in diabetic patients (P<0.05).
      The media-to-lumen ratio of resistance arteries was greater in hypertensives
      (0.083+/-0.002) compared with normotensive controls (0.059+/-0.003; P<0.05) and
      was even higher in diabetic hypertensive subjects (0.105+/-0.004; P<0.001 versus
      normotensive controls). The medial cross-sectional area was greater in diabetic
      and hypertensive patients compared with normotensive controls (P<0.001).
      Acetylcholine-induced relaxation was impaired in vessels from hypertensive
      patients and from patients with both diabetes mellitus and hypertension (P<0.05
      versus normotensive controls), whereas endothelium-independent vasorelaxation was
      similar in all groups. Despite effective antihypertensive treatment, resistance
      arteries from hypertensive diabetic patients showed marked remodeling, greater
      than that of vessels from untreated, nondiabetic, hypertensive subjects, in
      agreement with the high cardiovascular risk of subjects suffering from both
      diabetes and hypertension.

PMID- 14707159
TI  - Prolonged activation of the baroreflex produces sustained hypotension.
AB  - The role of baroreflexes in long-term control of arterial pressure is unresolved.
      To determine whether chronic activation of the baroreflex produces sustained
      hypotension, we developed a method for prolonged activation of the carotid
      baroreflex in conscious dogs. This was achieved by chronically implanting
      electrodes around both carotid sinuses and using an externally adjustable pulse
      generator to electrically activate the carotid baroreflex. Control values for
      mean arterial pressure (MAP) and heart rate were 93+/-3 mm Hg and 64+/-4 bpm,
      respectively. After control measurements, the carotid baroreflex was activated
      bilaterally for 7 days at a level that produced a prompt and substantial
      reduction in MAP, and for day 1 MAP was reduced to 75+/-4 mm Hg. Moreover, this
      hypotensive response was sustained throughout the entire 7 days of baroreflex
      activation (day 7, MAP=72+/-5 mm Hg). During prolonged baroreflex activation,
      heart rate decreased in parallel with MAP, although the changes were not as
      pronounced (day 7, heart rate=51+/-3 bpm). Prolonged baroreflex activation was
      also associated with approximately 35% reduction in plasma norepinephrine
      concentration (control=87+/-15 pg/mL). After baroreflex activation, hemodynamic
      measures and plasma levels of norepinephrine returned to control levels.
      Interestingly, despite the pronounced fall in MAP, plasma renin activity did not
      increase during prolonged baroreflex activation. These data indicate that
      prolonged baroreflex activation can lead to substantial reductions in MAP by
      suppressing the sympathetic nervous system. Furthermore, sustained
      sympathoinhibitory effects on renin secretion may play an important role in
      mediating the long-term hypotensive response.

PMID- 14707160
TI  - Role of adrenergic activity in pressor responses to chronic melanocortin receptor
      activation.
AB  - Acute studies have shown that MC3/4-R stimulation increases sympathetic activity,
      but the role of adrenergic activation in mediating the cardiovascular and renal
      responses to chronic melanocortin 3- and 4-receptor (MC3/4-R) activation is
      unknown. The present study tested whether chronic MC3/4-R activation raises blood
      pressure and whether these changes are attenuated by alpha1+beta-adrenergic
      blockade. Rats were instrumented with an intracerebroventricular (ICV) cannula
      and arterial and venous catheters for measurements of mean arterial pressure
      (MAP) and heart rate (HR) 24 hours per day, and intravenous infusions. After
      control measurements, rats were intravenously infused with either saline vehicle
      (n=7) or alpha1+ beta-adrenergic antagonists (n=6, terazosin+propranolol, 10
      mg/kg per day each) for 21 days. Five days after starting the vehicle or
      adrenergic blockade, the MC3/4-R agonist, MTII (10 ng/h), was infused ICV for 11
      days followed by a 5-day recovery period. Another group of rats was infused with
      the adrenergic antagonists for 21 days but received the saline vehicle ICV for 11
      days (n=7). MC3/4-R activation decreased food intake from 21+/-1 to 8+/-2 g/d by
      day 3 of MC3/4-R activation, and increased MAP and HR by an average of 8+/-2 mm
      Hg and 9+/-5 bpm, respectively. Adrenergic blockade did not alter the MC3/4-R
      mediated decrease in food intake but abolished the increases in MAP and HR (1+/-2
      mm Hg and -12+/-5 bpm, respectively, compared with control). ICV vehicle infusion
      during adrenergic blockade did not alter food intake or MAP. Glomerular
      filtration rate was unchanged in both the vehicle-infused and adrenergic blocked
      rats during MC3/4-R activation. These results indicate that the chronic actions
      of MC3/4-R activation on MAP and HR are mediated by adrenergic activation.

PMID- 14707161
TI  - Decreased endothelium-dependent NO-cGMP vascular relaxation and hypertension in
      growth-restricted rats on a high-salt diet.
AB  - Low birth weight caused by placental insufficiency increases the risk of
      hypertension in young adults, particularly while ingesting a high-salt diet;
      however, the vascular mechanisms involved are unclear. We tested whether
      intrauterine fetal growth restriction results in salt-sensitive offspring that
      exhibit impaired endothelium-dependent relaxation, enhanced vascular contraction,
      and hypertension during high-salt diet feeding. Male offspring of control
      pregnant rats and pregnant rats with reduced uterine perfusion pressure
      (intrauterine growth restricted [IUGR]) were fed either a normal-sodium (NS, 1%)
      or a high-sodium (HS, 8%) diet. Body weight was less in IUGR/NS and IUGR/HS than
      in NS and HS rats. Arterial pressure was greater in IUGR/NS (144+/-4 mm|Hg) than
      in NS (131+/-3 mm|Hg) rats and far greater in IUGR/HS (171+/-12 mm|Hg) than in HS
      (129+/-2 mm|Hg) rats. In isolated, endothelium-intact aortic strips,
      phenylephrine (Phe, 10(-5) mol/L) caused an increase in active stress that was
      greater in IUGR/NS (13.9+/-0.9 N/m2) than in NS (8.5+/-0.6 N/m2) animals and far
      greater in IUGR/HS (18.2+/-1.2 N/m2) than in HS (9.4+/-0.8x10(4) N/m2) rats.
      Acetylcholine caused relaxation of the Phe-mediated contraction and induced
      vascular nitrite/nitrate production that was less in IUGR/NS than in NS animals
      and far less in IUGR/HS than in HS rats. N(G)-nitro-L-arginine methyl ester,
      which inhibits nitric oxide (NO) synthase, or ODQ, which inhibits cGMP production
      in smooth muscle, inhibited acetylcholine relaxations and enhanced Phe
      contractions in NS and HS rats but not in IUGR/NS or IUGR/HS rats. Endothelium
      removal enhanced Phe-induced stress in NS and HS rats but not in IUGR/NS or
      IUGR/HS rats. Thus, endothelium-dependent relaxation via the NO-cGMP pathway is
      inhibited in systemic vessels of IUGR rats, particularly during intake of an HS
      diet. This might explain the increased vasoconstriction and arterial pressure in
      low-birth-weight offspring during ingestion of an HS diet.

PMID- 14707162
TI  - Two quantitative trait loci affect ACE activities in Mexican-Americans.
AB  - Angiotensin-converting enzyme (ACE) activity is highly heritable and has been
      associated with cardiovascular disease. We are studying the effects of genes and
      environmental factors on hypertension and related phenotypes, such as ACE
      activity, in Mexican-American families. In the current study, we performed
      multipoint linkage analysis to search for quantitative trait loci (QTLs) that
      affect ACE activities on data from 793 individuals from 29 pedigrees from the San
      Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log
      of the odds [LOD]=4.57, genomic P=0.003) that a QTL for ACE activity is located
      on chromosome 17 near the ACE structural locus. We subsequently performed linkage
      analyses conditional on the effect of this QTL and obtained strong evidence
      (LOD=3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated
      the ACEIns/Del genotypes in our analyses and removed the evidence for the
      chromosome 17 QTL (maximum LOD=0.60); however, we retained our evidence for the
      QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked
      to ACE and is in strong disequilibrium with the insertion/deletion polymorphism,
      which is consistent with other reports. We also have evidence that an additional
      QTL affects ACE activity. Identification of this additional QTL might lead to
      alternate means of prophylaxis.

PMID- 14707163
TI  - Autosomal-dominant hypertension with type E brachydactyly is caused by
      rearrangement on the short arm of chromosome 12.
AB  - We are studying a Turkish family with autosomal-dominant hypertension and
      brachydactyly; affected persons die of stroke before 50 years of age. With
      interphase fluorescence in situ hybridization, we found a chromosome 12p
      deletion, reinsertion, and inversion in affected persons. This finding suggested
      that the hypertension could be caused by one or more of 3 genes, the ATP
      dependent potassium channel Kir6.1, its regulator the sulfonyl urea receptor
      SUR2, and the phosphodiesterase PDE3A. We further studied 6 affected and 4
      nonaffected persons. Buttocks biopsies were done, small vessels were tested on a
      myograph, and mRNA was extracted. We performed forearm blood flow studies with
      intrabrachial artery diazoxide, isoproterenol, and milrinone infusions. Systemic
      pharmacological testing was done with intravenous diazoxide, nitroprusside, and
      isoproterenol. PDE3A mRNA was high in vessels from 3 affected subjects, but not
      high in 3 others. The vessels responded similarly to forskolin, with or without
      glibenclamide, and to cromakalim. However, there was a suggestion that the
      dilatation after milrinone might be exaggerated. The forearm infusion studies
      showed no differences in the responses to diazoxide, isoproterenol, or milrinone.
      Systemically, affected persons showed a greater blood pressure response to
      diazoxide and nitroprusside, and a greater heart rate response to isoproterenol
      than nonaffected persons. The results shed doubt on Kir6.1 and SUR2. The
      differences in PDE3A expression and responses may be the result of hypertension
      rather than the cause. Although our 3 candidate genes are no longer likely, the
      rearrangement we describe greatly enhances the perspectives of this project.

PMID- 14707164
TI  - Role of endothelin-1 in blood pressure regulation in a rat model of visceral
      obesity and hypertension.
AB  - Endothelial dysfunction has been suggested to play an important role in the
      development of obesity-induced hypertension. Because endothelin release increases
      in response to endothelial damage, we examined whether endothelin-1 contributes
      to increased arterial pressure in a model of visceral obesity produced by feeding
      Sprague-Dawley rats a high-fat (HF) diet (40% fat w/w, n=6) for 12 months.
      Arterial and venous catheters were implanted for measurement of mean arterial
      pressure (MAP) and heart rate (HR) 24 hours per day and intravenous infusions.
      After a 5-day control period, rats were infused with the selective endothelin-1
      type A receptor (ET-A) blocker ABT-627 (2.5 mg/kg per day, IV) for 9 days,
      followed by a recovery period. Rats fed a standard chow (normal fat, or NF,
      group: n=6) for 12 months were also infused with ET-A blocker and were used as
      controls. Compared with NF rats, HF rats had higher MAP (113+/-4 versus 98+/-2 mm
      Hg), increased visceral fat (18.7+/-2.0 versus 10.8+/-1.4 g), and 3.2-fold
      increase in plasma leptin despite similar total body weight gain. Long-term ET-A
      blockade markedly reduced MAP in HF (-14+/-3 mm Hg) and NF (-14+/-2 mm Hg), but
      it had no effect on HR, GFR, or PRA. These results indicate that a long-term HF
      diet may cause visceral obesity and increased MAP, even in the absence of major
      changes in total body weight. Endothelin-1 appears to play an important role in
      the maintenance of arterial pressure in rats fed HF and NF diets, but it does not
      appear to contribute to increased MAP in this model of diet-induced hypertension.

PMID- 14707165
TI  - Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin
      fish.
AB  - The pufferfish skeleton lacks ribs and pelvic fins, and has fused bones in the
      cranium and jaw. It has been hypothesized that this secondarily simplified
      pufferfish morphology is due to reduced complexity of the pufferfish Hox
      complexes. To test this hypothesis, we determined the genomic structure of Hox
      clusters in the Southern pufferfish Spheroides nephelus and interrogated genomic
      databases for the Japanese pufferfish Takifugu rubripes (fugu). Both species have
      at least seven Hox clusters, including two copies of Hoxb and Hoxd clusters, a
      single Hoxc cluster, and at least two Hoxa clusters, with a portion of a third
      Hoxa cluster in fugu. Results support genome duplication before divergence of
      zebrafish and pufferfish lineages, followed by loss of a Hoxc cluster in the
      pufferfish lineage and loss of a Hoxd cluster in the zebrafish lineage.
      Comparative analysis shows that duplicate genes continued to be lost for hundreds
      of millions of years, contrary to predictions for the permanent preservation of
      gene duplicates. Gene expression analysis in fugu embryos by in situ
      hybridization revealed evolutionary change in gene expression as predicted by the
      duplication-degeneration-complementation model. These experiments rule out the
      hypothesis that the simplified pufferfish body plan is due to reduction in Hox
      cluster complexity, and support the notion that genome duplication contributed to
      the radiation of teleosts into half of all vertebrate species by increasing
      developmental diversification of duplicate genes in daughter lineages.

PMID- 14707166
TI  - Bichir HoxA cluster sequence reveals surprising trends in ray-finned fish genomic
      evolution.
AB  - The study of Hox clusters and genes provides insights into the evolution of
      genomic regulation of development. Derived ray-finned fishes (Actinopterygii,
      Teleostei) such as zebrafish and pufferfish possess duplicated Hox clusters that
      have undergone considerable sequence evolution. Whether these changes are
      associated with the duplication(s) that produced extra Hox clusters is unresolved
      because comparison with basal lineages is unavailable. We sequenced and analyzed
      the HoxA cluster of the bichir (Polypterus senegalus), a phylogenetically basal
      actinopterygian. Independent lines of evidence indicate that bichir has one HoxA
      cluster that is mosaic in its patterns of noncoding sequence conservation and
      gene retention relative to the HoxA clusters of human and shark, and the
      HoxAalpha and HoxAbeta clusters of zebrafish, pufferfish, and striped bass. HoxA
      cluster noncoding sequences conserved between bichir and euteleosts indicate that
      novel cis-sequences were acquired in the stem actinopterygians and maintained
      after cluster duplication. Hence, in the earliest actinopterygians, evolution of
      the single HoxA cluster was already more dynamic than in human and shark. This
      tendency peaked among teleosts after HoxA cluster duplication.

PMID- 14707167
TI  - Mapping and initial analysis of human subtelomeric sequence assemblies.
AB  - Physical mapping data were combined with public draft and finished sequences to
      derive subtelomeric sequence assemblies for each of the 41 genetically distinct
      human telomere regions. Sequence gaps that remain on the reference telomeres are
      generally small,well-defined,and for the most part,restricted to regions directly
      adjacent to the terminal (TTAGGG)n tract. Of the 20.66 Mb of subtelomeric DNA
      analyzed, 3.01 Mb are subtelomeric repeat sequences (Srpt),and an additional 2.11
      Mb are segmental duplications. The subtelomeric sequence assemblies are enriched
      >25-fold in short,internal (TTAGGG)n-like sequences relative to the rest of the
      genome; a total of 114 (TTAGGG)n-like islands were found,55 within Srpt
      regions,35 within one-copy regions,11 at one-copy/Srpt or Srpt/segmental
      duplication boundaries,and 13 at the telomeric ends of assemblies. Transcripts
      were annotated in each assembly,noting their mapping coordinates relative to
      their respective telomere and whether they originate in duplicated DNA or single
      copy DNA. A total of 697 transcripts were found in 15.53 Mb of one-copy DNA,76
      transcripts in 2.11 Mb of segmentally duplicated DNA,and 168 transcripts in 3.01
      Mb of Srpt sequence. This overall transcript density is similar (within
      approximately 10%) to that found genome-wide. Zinc finger-containing genes and
      olfactory receptor genes are duplicated within and between multiple telomere
      regions.

PMID- 14707168
TI  - Coelomata and not Ecdysozoa: evidence from genome-wide phylogenetic analysis.
AB  - Relative positions of nematodes, arthropods, and chordates in animal phylogeny
      remain uncertain. The traditional tree topology joins arthropods with chordates
      in a coelomate clade, whereas nematodes, which lack a coelome, occupy a basal
      position. However, the current leading hypothesis, based on phylogenetic trees
      for 18S ribosomal RNA and several proteins, joins nematodes with arthropods in a
      clade of molting animals, Ecdysozoa. We performed a phylogenetic analysis of over
      500 sets of orthologous proteins, which are represented in plants, animals, and
      fungi, using maximum likelihood, maximum parsimony, and distance methods.
      Additionally, to increase the statistical power of topology tests, the same
      methods were applied to concatenated alignments of subunits of eight conserved
      macromolecular complexes. The majority of the methods, when applied to most of
      the orthologous clusters, both concatenated and individual, grouped the fly with
      humans to the exclusion of the nematode, in support of the coelomate phylogeny.
      Trees were also constructed using information on insertions and deletions in
      orthologous proteins, combinations of domains in multidomain proteins, and
      presence-absence of species in clusters of orthologs. All of these approaches
      supported the coelomate clade and showed concordance between evolution of protein
      sequences and higher-level evolutionary events, such as domain fusion or gene
      loss.

PMID- 14707169
TI  - Elevated rates of protein secretion, evolution, and disease among tissue-specific
      genes.
AB  - Variation in gene expression has been held responsible for the functional and
      morphological specialization of tissues. The tissue specificity of genes is known
      to correlate positively with gene evolution rates. We show here, using large data
      sets, that when a gene is expressed highly in a small number of tissues, its
      protein is more likely to be secreted and more likely to be mutated in genetic
      diseases with Mendelian inheritance. We find that secreted proteins are evolving
      at faster rates than nonsecreted proteins, and that their evolutionary rates are
      highly correlated with tissue specificity. However, the impact of secretion on
      evolutionary rates is countered by tissue-specific constraints that have been
      held constant over the past 75 million years. We find that disease genes are
      underrepresented among intracellular and slowly evolving housekeeping genes.
      These findings illuminate major selective pressures that have shaped the gene
      repertoires expressed in different mammalian tissues.

PMID- 14707170
TI  - An abundance of bidirectional promoters in the human genome.
AB  - The alignment of full-length human cDNA sequences to the finished sequence of the
      human genome provides a unique opportunity to study the distribution of genes
      throughout the genome. By analyzing the distances between 23,752 genes, we
      identified a class of divergently transcribed gene pairs, representing more than
      10% of the genes in the genome, whose transcription start sites are separated by
      less than 1000 base pairs. Although this bidirectional arrangement has been
      previously described in humans and other species, the prevalence of bidirectional
      gene pairs in the human genome is striking, and the mechanisms of regulation of
      all but a few bidirectional genes are unknown. Our work shows that the
      transcripts of many bidirectional pairs are coexpressed, but some are
      antiregulated. Further, we show that many of the promoter segments between two
      bidirectional genes initiate transcription in both directions and contain shared
      elements that regulate both genes. We also show that the bidirectional
      arrangement is often conserved among mouse orthologs. These findings demonstrate
      that a bidirectional arrangement provides a unique mechanism of regulation for a
      significant number of mammalian genes.

PMID- 14707171
TI  - Ordered partitioning reveals extended splice-site consensus information.
AB  - Using recently available cDNA and genomic data (Berkeley Drosophila Genome
      Project; http://www.fruitfly.org), we computed a large sample of 10,057
      Drosophila splice sites. An information-theoretic analysis of the nucleotide
      sequences adjacent to these splice sites showed a strong correlation between the
      sizes of introns and exons and the levels of information, which is a measure of
      sequence conservation. The strong correlation permitted us to determine extensive
      consensus sequences at the donor and acceptor sites of longer introns. These
      sequences were further refined and extended by examining the information in
      regions around splice sites that only partially matched the consensus. The
      correlation between length and information provided the basis for determining
      alternative consensus arrangements associated with shorter introns, as well as
      general base-composition preferences that likely promote spliceosome function. We
      also observed a correlation between information near splice sites and the lengths
      of nonadjacent introns, indicating that there are long-range effects spanning
      multiple introns. The ordered partitioning approach used in this analysis may
      become increasingly useful as large genomic data sets become available.

PMID- 14707172
TI  - Identification of antibiotic stress-inducible promoters: a systematic approach to
      novel pathway-specific reporter assays for antibacterial drug discovery.
AB  - As present antibiotics therapy becomes increasingly ineffectual, new technologies
      are required to identify and develop novel classes of antibacterial agents. An
      attractive alternative to the classical target-based approach is the use of
      promoter-inducible reporter assays for high-throughput screening. The wide usage
      of these assays is, however, limited by the small number of specifically
      responding promoters that are known at present. This work describes a novel
      approach for identifying genetic regulators that are suitable for the design of
      pathway-specific assays. The basis for the proposed strategy is a large set of
      antibiotics-triggered expression profiles ("Reference Compendium"). Pattern
      recognition algorithms applied to the expression data pinpoint the relevant
      transcription-factor-binding sites in whole-genome sequences. Using this
      technique, we constructed a fatty-acid-pathway-specific reporter assay that is
      based on a novel stress-inducible promoter. In a proof-of-principle experiment,
      this assay was shown to enable screening for new small-molecule inhibitors of
      bacterial growth.

PMID- 14707173
TI  - A cross-genomic approach for systematic mapping of phenotypic traits to genes.
AB  - We present a computational method for de novo identification of gene function
      using only cross-organismal distribution of phenotypic traits. Our approach
      assumes that proteins necessary for a set of phenotypic traits are preferentially
      conserved among organisms that share those traits. This method combines organism
      to-phenotype associations,along with phylogenetic profiles,to identify proteins
      that have high propensities for the query phenotype; it does not require the use
      of any functional annotations for any proteins. We first present the statistical
      foundations of this approach and then apply it to a range of phenotypes to assess
      how its performance depends on the frequency and specificity of the phenotype.
      Our analysis shows that statistically significant associations are possible as
      long as the phenotype is neither extremely rare nor extremely common; results on
      the flagella,pili, thermophily,and respiratory tract tropism phenotypes suggest
      that reliable associations can be inferred when the phenotype does not arise from
      many alternate mechanisms.

PMID- 14707174
TI  - High-throughput MALDI-TOF discovery of genomic sequence polymorphisms.
AB  - We describe a comparative sequencing strategy that is based on matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)
      analyses of complete base-specific cleavage reactions of a target sequence. The
      target is converted to a DNA/RNA mosaic structure after PCR amplification using
      in vitro transcription. Cleavage with defined specificity is achieved by
      ribonucleases. The set of cleavage products is subjected to mass spectrometry
      without prior fractionation. The presented resequencing assay is particularly
      useful for single-nucleotide polymorphism (SNP) discovery. The combination of
      mass spectra from four complementary cleavage reactions detects approximately 98%
      of all possible homozygous and heterozygous SNPs in target sequences with a
      length of up to 500 bases. In general, both the identity and location of the
      sequence variation are determined. This was exemplified by the discovery of SNPs
      in the human gene coding for the cholesteryl ester transfer protein using a panel
      of 96 genomic DNAs.

PMID- 14707175
TI  - Analysis of sequence variations in several human genes using phosphoramidite bond
      DNA fragmentation and chip-based MALDI-TOF.
AB  - The challenge in the postgenome era is to measure sequence variations over large
      genomic regions in numerous patient samples. This massive amount of work can only
      be completed if more accurate, cost-effective, and high-throughput solutions
      become available. Here we describe a novel DNA fragmentation approach for single
      nucleotide polymorphism (SNP) discovery and sequence validation. The base
      specific cleavage is achieved by creating primer extension products, in which
      acid-labile phosphoramidite (P-N) bonds replace the 5' phosphodiester bonds of
      newly incorporated pyrimidine nucleotides. Sequence variations are detected by
      hydrolysis of this acid-labile bond and MALDI-TOF analysis of the resulting
      fragments. In this study, we developed a robust protocol for P-N-bond
      fragmentation and investigated additional ways to improve its sensitivity and
      reproducibility. We also present the analysis of several human genomic targets
      ranging from 100-450 bp in length. By using a semiautomated sample processing
      protocol, we investigated an array of SNPs within a 240-bp segment of the NFKBIA
      gene in 48 human DNA samples. We identified and measured frequencies for the two
      common SNPs in the 3'UTR of NFKBIA (separated by 123 bp) and then confirmed these
      values in an independent genotyping experiment. The calculated allele frequencies
      in white and African American groups differed significantly, yet both fit Hardy
      Weinberg expectations. This demonstrates the utility and effectiveness of PN-bond
      DNA fragmentation and subsequent MALDI-TOF MS analysis for the high-throughput
      discovery and measurement of sequence variations in fragments up to 0.5 kb in
      length in multiple human blood DNA samples.

PMID- 14707176
TI  - Computational gene prediction using multiple sources of evidence.
AB  - This article describes a computational method to construct gene models by using
      evidence generated from a diverse set of sources, including those typical of a
      genome annotation pipeline. The program, called Combiner, takes as input a
      genomic sequence and the locations of gene predictions from ab initio gene
      finders, protein sequence alignments, expressed sequence tag and cDNA alignments,
      splice site predictions, and other evidence. Three different algorithms for
      combining evidence in the Combiner were implemented and tested on 1783 confirmed
      genes in Arabidopsis thaliana. Our results show that combining gene prediction
      evidence consistently outperforms even the best individual gene finder and, in
      some cases, can produce dramatic improvements in sensitivity and specificity.

PMID- 14707177
TI  - Hierarchical scaffolding with Bambus.
AB  - The output of a genome assembler generally comprises a collection of contiguous
      DNA sequences (contigs) whose relative placement along the genome is not defined.
      A procedure called scaffolding is commonly used to order and orient these contigs
      using paired read information. This ordering of contigs is an essential step when
      finishing and analyzing the data from a whole-genome shotgun project. Most recent
      assemblers include a scaffolding module; however, users have little control over
      the scaffolding algorithm or the information produced. We thus developed a
      general-purpose scaffolder, called Bambus, which affords users significant
      flexibility in controlling the scaffolding parameters. Bambus was used recently
      to scaffold the low-coverage draft dog genome data. Most significantly, Bambus
      enables the use of linking data other than that inferred from mate-pair
      information. For example, the sequence of a completed genome can be used to guide
      the scaffolding of a related organism. We present several applications of Bambus:
      support for finishing, comparative genomics, analysis of the haplotype structure
      of genomes, and scaffolding of a mammalian genome at low coverage. Bambus is
      available as an open-source package from our Web site.

PMID- 14707178
TI  - EnsMart: a generic system for fast and flexible access to biological data.
AB  - The EnsMart system (www.ensembl.org/EnsMart) provides a generic data warehousing
      solution for fast and flexible querying of large biological data sets and
      integration with third-party data and tools. The system consists of a query
      optimized database and interactive, user-friendly interfaces. EnsMart has been
      applied to Ensembl, where it extends its genomic browser capabilities,
      facilitating rapid retrieval of customized data sets. A wide variety of complex
      queries, on various types of annotations, for numerous species are supported.
      These can be applied to many research problems, ranging from SNP selection for
      candidate gene screening, through cross-species evolutionary comparisons, to
      microarray annotation. Users can group and refine biological data according to
      many criteria, including cross-species analyses, disease links, sequence
      variations, and expression patterns. Both tabulated list data and biological
      sequence output can be generated dynamically, in HTML, text, Microsoft Excel, and
      compressed formats. A wide range of sequence types, such as cDNA, peptides,
      coding regions, UTRs, and exons, with additional upstream and downstream regions,
      can be retrieved. The EnsMart database can be accessed via a public Web site, or
      through a Java application suite. Both implementations and the database are
      freely available for local installation, and can be extended or adapted to 'non
      Ensembl' data sets.

PMID- 14707180
TI  - Western medical journals and the 10/90 problem.

PMID- 14707179
TI  - A whole-genome mouse BAC microarray with 1-Mb resolution for analysis of DNA copy
      number changes by array comparative genomic hybridization.
AB  - Microarray-based comparative genomic hybridization (CGH) has become a powerful
      method for the genome-wide detection of chromosomal imbalances. Although BAC
      microarrays have been used for mouse CGH studies, the resolving power of these
      analyses was limited because high-density whole-genome mouse BAC microarrays were
      not available. We therefore developed a mouse BAC microarray containing 2803
      unique BAC clones from mouse genomic libraries at 1-Mb intervals. For the general
      amplification of BAC clone DNA prior to spotting, we designed a set of three
      novel degenerate oligonucleotide-primed (DOP) PCR primers that preferentially
      amplify mouse genomic sequences while minimizing unwanted amplification of
      contaminating Escherichia coli DNA. The resulting 3K mouse BAC microarrays
      reproducibly identified DNA copy number alterations in cell lines and primary
      tumors, such as single-copy deletions, regional amplifications, and aneuploidy.

PMID- 14707184
TI  - Courting hyperlipidemia.

PMID- 14707186
TI  - Missing information on DEET.

PMID- 14707187
TI  - Bodychecking in hockey.

PMID- 14707189
TI  - Bodychecking in hockey.

PMID- 14707190
TI  - Bodychecking in hockey.

PMID- 14707191
TI  - Bodychecking in hockey.

PMID- 14707193
TI  - Bodychecking in hockey.

PMID- 14707194
TI  - Prehospital intubation and SARS.

PMID- 14707195
TI  - Prehospital intubation and SARS.

PMID- 14707196
TI  - Prehospital intubation and SARS.

PMID- 14707197
TI  - Prehospital intubation and SARS.

PMID- 14707198
TI  - Revisiting Helsinki.

PMID- 14707201
TI  - Revisiting Helsinki.

PMID- 14707206
TI  - New guidelines for severe respiratory infections.

PMID- 14707212
TI  - The tribulations of community-based trials.

PMID- 14707213
TI  - Patient protection laws and the issue of consensual sexual relationships with
      physicians.

PMID- 14707215
TI  - Hot flashes...in January.

PMID- 14707217
TI  - A distinctive case of dysphagia.

PMID- 14707216
TI  - Is there sustained renal benefit from previous intensive insulin therapy in
      people with type 1 diabetes?

PMID- 14707219
TI  - Interpretation of diagnostic laboratory tests for severe acute respiratory
      syndrome: the Toronto experience.
AB  - BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) began in
      Canada in February 2003. The initial diagnosis of SARS was based on clinical and
      epidemiological criteria. During the outbreak, molecular and serologic tests for
      the SARS-associated coronavirus (SARS-CoV) became available. However, without a
      "gold standard," it was impossible to determine the usefulness of these tests. We
      describe how these tests were used during the first phase of the SARS outbreak in
      Toronto and offer some recommendations that may be useful if SARS returns.
      METHODS: We examined the results of all diagnostic laboratory tests used in 117
      patients admitted to hospitals in Toronto who met the Health Canada criteria for
      suspect or probable SARS. Focusing on tests for SARS-CoV, we attempted to
      determine the optimal specimen types and timing of specimen collection. RESULTS:
      Diagnostic test results for SARS-CoV were available for 110 of the 117 patients.
      SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction
      (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. Serologic test
      results of convalescent samples were positive in 50 (96.2%) of 52 patients for
      whom paired serum samples were collected during the acute and convalescent phases
      of the illness. Of the 110 patients, 78 (70.9%) had specimens that tested
      positive by means of RT-PCR, serologic testing or both methods. The proportion of
      RT-PCR test results that were positive was similar between patients who met the
      criteria for suspect SARS (50.8%, 95% confidence interval [CI] 38.4%-63.2%) and
      those who met the criteria for probable SARS (58.0%, 95% CI 44.2%-70.7%). SARS
      CoV was detected in nasopharyngeal swabs in 33 (32.4%) of 102 patients, in stool
      specimens in 19 (63.3%) of 30 patients, and in specimens from the lower
      respiratory tract in 10 (58.8%) of 17 patients. INTERPRETATION: These findings
      suggest that the rapid diagnostic tests in use at the time of the initial
      outbreak lack sufficient sensitivity to be used clinically to rule out SARS. As
      tests for SARS-CoV continue to be optimized, evaluation of the clinical
      presentation and elucidation of a contact history must remain the cornerstone of
      SARS diagnosis. In patients with SARS, specimens taken from the lower respiratory
      tract and stool samples test positive by means of RT-PCR more often than do
      samples taken from other areas.

PMID- 14707220
TI  - Leprosy in Toronto: an analysis of 184 imported cases.
AB  - BACKGROUND: Leprosy is a rare but serious mycobacterial infection. Immigration
      from areas where the disease is endemic has resulted in the importation of
      leprosy into countries where it is not endemic and where physicians and health
      care workers have little or no experience in diagnosis and therapy. In this study
      we characterized leprosy patients seen in a tropical disease unit that manages
      most of the reported leprosy cases in Canada. METHODS: We reviewed the clinical
      records of all 184 leprosy patients who were referred to the Tropical Disease
      Unit at Toronto General Hospital between 1979 and 2002 and abstracted demographic
      and clinical information. RESULTS: Patients were more likely to be male (122 or
      66.3%) and of Indian (44 or 23.9%), Filipino (49 or 26.6%) or Vietnamese (37 or
      20.1%) origin. Patients experienced symptoms for a mean of 4.8 years before
      referral to the Tropical Disease Unit. Most had no family history of leprosy
      (152/172 or 88.4%). Most patients presented with either borderline tuberculoid
      (80 or 43.5%) or borderline lepromatous (37 or 20.1%) disease. On average,
      patients presented with 5.8 skin lesions. Upper- and lower-extremity nerve
      dysfunction was common at presentation, with up to one-third of patients
      demonstrating either sensory or motor loss. A significantly greater lag time to
      presentation was observed in patients who emigrated from low-prevalence regions
      (p < 0.001). INTERPRETATION: Leprosy is a chronic infectious disease that is
      associated with serious morbidity if left untreated. Leprosy is uncommon in
      developed countries, but it is important for physicians to have a high index of
      suspicion when a foreign-born patient presents with chronic dermatitis and
      peripheral nerve involvement.

PMID- 14707221
TI  - Laboratory tests for SARS: powerful or peripheral?

PMID- 14707222
TI  - Medical journals and global medicine.

PMID- 14707223
TI  - Weapons of mass salvation: Canada's role in improving the health of the global
      poor.

PMID- 14707224
TI  - Why SARS will not return: a polemic.

PMID- 14707226
TI  - Leprosy: a primer for Canadian physicians.
AB  - Leprosy is a rare but serious infectious disease caused by Mycobacterium leprae.
      While global prevalence of the disease is decreasing, increasing rates of
      immigration from countries where leprosy is endemic have led to the recognition
      of this illness in North America. Classically, leprosy presents as hypopigmented
      cutaneous macules along with sensory and motor peripheral neuropathies, although
      the clinical manifestations vary along a disease spectrum. In addition to primary
      infection, patients may undergo a "reaction," an acute inflammatory response to
      the mycobacterium, which leads to pain and erythema of skin lesions and dangerous
      neuritis. Reactions can occur at any time during the course of leprosy, but they
      tend to be precipitated by treatment. They are a significant cause of impaired
      quality of life due to marked nerve damage and thus warrant prompt intervention.
      Although leprosy may have a protracted onset and be difficult to recognize, cure
      is achievable with appropriate multidrug therapy. Because untreated leprosy can
      result in permanent, irreversible nerve damage and secondary transmission, early
      diagnosis and treatment are essential to minimize morbidity.

PMID- 14707231
TI  - Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by
      independent researchers, pharmaceutical suppliers, and the Food and Drug
      Administration.
AB  - BACKGROUND AND PURPOSE: Since the 1999 identification of clopidogrel-associated
      thrombotic thrombocytopenic purpura (TTP) through independent active
      surveillance, subsequent cases have been identified by pharmaceutical suppliers
      of clopidogrel and the Food and Drug Administration (FDA). For cases of
      clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the
      quality and timeliness of data from 3 reporting systems-independent active
      surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and
      identified prognostic factors associated with mortality. METHODS: This study
      assessed the completeness of information on TTP diagnosis, treatment response,
      and causality from the 3 reporting systems. In addition, predictors of mortality
      were identified through classification tree analysis. RESULTS: Completeness,
      timeliness, and certainty of diagnosis were best for cases obtained by active
      surveillance, intermediate for cases reported to the pharmaceutical supplier, and
      poorest for cases reported directly to the FDA. Clopidogrel had been used for
      </=2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP
      was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP
      increased the likelihood of survival (100% versus 27.3%, P<0.001). CONCLUSIONS:
      Compared with reports submitted by suppliers or the FDA, reports obtained through
      active surveillance provided timelier and more complete information. Clopidogrel
      associated TTP often occurs within 2 weeks of drug initiation, occasionally
      relapses, and has a high mortality if not treated promptly.

PMID- 14707232
TI  - Hemicraniectomy for massive middle cerebral artery territory infarction: a
      systematic review.
AB  - BACKGROUND AND PURPOSE: Hemicraniectomy and durotomy have been proposed in many
      small series to relieve intracranial hypertension and tissue shifts in patients
      with large hemispheric infarcts, thereby preventing death from herniation. Our
      objective was to review the literature to identify patients most likely to
      benefit from hemicraniectomy. METHODS: All available individual cases from the
      English literature were reviewed and analyzed to determine whether age, vascular
      territory of infarction, side of infarction, reported time to surgery, and signs
      of herniation predict outcome in patients after hemicraniectomy. All studies
      included were retrospective and uncontrolled; there were no randomized controlled
      trials. RESULTS: Of 15 studies screened, 12 studies describing 129 patients met
      the criteria for analysis; 9 patients treated at our institution were added, for
      a total of 138 patients. After a minimum follow-up of 4 months, 10 patients (7%)
      were functionally independent, 48 (35%) were mildly to moderately disabled, and
      80 (58%) died or were severely disabled. Of 75 patients who were >50 years of
      age, 80% were dead or severely disabled compared with 32% of 63 patients <or=50
      years of age (P<0.00001). The timing of surgery, hemisphere infarcted, presence
      of signs of herniation before surgery, and involvement of other vascular
      territories did not significantly affect outcome. CONCLUSIONS: Age may be a
      crucial factor in predicting functional outcome after hemicraniectomy in patients
      with large middle cerebral artery territory infarction.

PMID- 14707233
TI  - Differential pattern of tissue plasminogen activator-induced proximal middle
      cerebral artery recanalization among stroke subtypes.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate the timing, speed, and degree of
      tissue plasminogen activator (tPA)-induced recanalization in patients with
      proximal middle cerebral artery (MCA) occlusion of different stroke subtypes.
      METHODS: We evaluated 72 patients with acute stroke caused by proximal MCA
      occlusion treated with intravenous tPA in <3 hours. Transcranial Doppler
      monitoring of recanalization was conducted during tPA infusion and at 6 hours.
      Strokes were categorized as large-vessel disease strokes, cardioembolic strokes,
      or strokes of undetermined origin according to Trial of Org 10172 in Acute Stroke
      Treatment criteria. RESULTS: During 1-hour tPA infusion, recanalization occurred
      in 34 patients (47%); 32% showed a sudden, 50% showed a stepwise, and 18% showed
      a slow pattern of recanalization. One-hour recanalization was more frequent in
      patients with cardioembolic stroke (59%) compared with large-vessel disease (8%)
      and undetermined origin (50%) strokes. A cardiac source of emboli was identified
      in 81% of patients who showed a sudden clot breakup during tPA infusion. Rate of
      complete recanalization at 6 hours was higher (P=0.006) in patients with
      cardioembolic stroke (50%) compared with other stroke subtypes (27%). Sudden
      recanalization was associated (P=0.002) with a higher degree of neurological
      improvement at 24 hours compared with stepwise, slow, and no recanalization. A
      graded response in long-term outcome was observed in relation to the speed of
      clot lysis during tPA administration. CONCLUSIONS: We demonstrate that the
      pattern of tPA-induced MCA recanalization differs among stroke subtypes. Early
      recanalization was more frequent, faster, and more complete in patients with
      cardioembolic stroke compared with other stroke subtypes.

PMID- 14707234
TI  - Continuous 15-year decrease in incidence and mortality of stroke in Finland: the
      FINSTROKE study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to analyze the incidence
      and mortality trends in stroke events among persons 25 to 74 years of age in
      Finland during 1983 to 1997. METHODS: The population-based FINSTROKE register
      recorded 5650 new strokes among persons 25 to 74 years of age in 2 geographical
      areas of Finland: 2770 in the Kuopio area (east central Finland) and 2880 in
      Turku (southwestern Finland). Of these, 3065 were men and 2585 were women.
      RESULTS: The rates of acute stroke events fell during the whole study period in
      both men and women. In both FINSTROKE areas combined, the average annual decline
      in the age-standardized incidence of first stroke events was 2.0% (95% confidence
      interval [CI], -2.8 to -1.2; P<0.001) among men and 1.7% (95% CI, -2.6 to -0.8;
      P<0.001) among women. The decline in the incidence of ischemic stroke was even
      steeper, 2.9%/y (95% CI, -4.9 to -1.1; P<0.001) among men and 3.1%/y (95% CI, 
      5.0 to -1.1; P<0.001) among women, whereas the incidence of intracerebral
      hemorrhage and subarachnoid hemorrhage did not change. Mortality from all stroke
      events declined in the FINSTROKE areas by 3.7%/y (95% CI, -5.3 to -2.0; P<0.001)
      among men and by 4.1%/y (95% CI, -5.9 to -2.4; P<0.001) among women. The 28-day
      case fatality of all stroke events also tended to decline, but the decline was of
      borderline statistical significance only (P=0.07 among men, P=0.05 among women).
      CONCLUSIONS: Incidence and mortality of stroke events declined significantly in
      these 2 register areas in Finland during the 15-year period of 1983 to 1997.

PMID- 14707235
TI  - Periodontal disease as a risk factor for ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Chronic infectious diseases may increase the risk of
      stroke. We investigated whether periodontal disease, including periodontitis and
      gingivitis, is a risk factor for cerebral ischemia. METHODS: We performed a case
      control study with 303 patients examined within 7 days after acute ischemic
      stroke or transient ischemic attack, 300 population controls, and 168 hospital
      controls with nonvascular and noninflammatory neurological diseases. All subjects
      received a complete clinical and radiographic dental examination. The individual
      mean clinical attachment loss measured at 4 sites per tooth served as the main
      indicator for periodontitis. RESULTS: Patients had higher clinical attachment
      loss than population (P<0.001) and hospital (P=0.010) controls. After adjustment
      for age, sex, number of teeth, vascular risk factors and diseases, childhood and
      adult socioeconomic conditions, and lifestyle factors, the risk of cerebral
      ischemia increased with more severe periodontitis. Subjects with severe
      periodontitis (mean clinical attachment loss >6 mm) had a 4.3-times-higher (95%
      confidence interval, 1.85 to 10.2) risk of cerebral ischemia than subjects with
      mild or without periodontitis (<or=3 mm). Severe periodontitis was a risk factor
      in men but not women and in younger (<60 years) but not older subjects.
      Periodontitis increased the risk of cerebral ischemia caused by large-artery
      atherosclerosis, cardioembolism, and cryptogenic etiology. Gingivitis and severe
      radiologic bone loss were also independently associated with the risk of cerebral
      ischemia, whereas caries was not. CONCLUSIONS: Our study indicates that
      periodontal disease, a treatable condition, is an independent risk factor for
      cerebral ischemia in men and younger subjects.

PMID- 14707236
TI  - Cortical microinfarcts and demyelination significantly affect cognition in brain
      aging.
AB  - BACKGROUND AND PURPOSE: Microvascular lesions are common in brain aging, but
      their clinical impact is debated. Methodological problems such as the masking
      effect of concomitant pathologies may explain discrepancies among previous
      studies. To evaluate the cognitive consequences of such lesions, we prospectively
      investigated elderly individuals with various degrees of cognitive impairment but
      without significant neurofibrillary tangle pathology or macrovascular lesions.
      METHODS: This was a clinicopathological study of 45 elderly individuals.
      Cognitive status was assessed prospectively with the Clinical Dementia Rating
      (CDR) scale; neuropathological evaluation included Abeta-protein deposition
      staging and bilateral semiquantitative assessment of cortical microinfarcts,
      focal cortical and white matter glioses, and diffuse white matter and
      periventricular demyelination. RESULTS: In a univariate logistic regression
      model, cortical microinfarcts explained 36.1% of the variability in CDR;
      periventricular demyelination, 10.6%; and diffuse white matter demyelination,
      4.6%. After controlling for age and Abeta-protein deposition, cortical
      microinfarcts were the best predictor of cognitive status (19.9% of CDR
      variability), whereas periventricular and diffuse white matter demyelination
      accounted for 9.7% and 5.4% of CDR variability, respectively. Altogether, these 3
      types of microvascular lesions explained 27.9% of the clinical variability. Focal
      cortical and white matter glioses were not related to clinical outcome.
      CONCLUSIONS: Our data imply that cortical microinfarcts and both periventricular
      and deep white matter demyelination contribute significantly to the progression
      of cognitive deficits in brain aging. In contrast, the neuropathological
      evaluation of focal cortical and white matter gliosis has no clinical validity.

PMID- 14707238
TI  - Crowd pleasers.

PMID- 14707237
TI  - Time for humanity from doctors towards patients.

PMID- 14707239
TI  - BookPower.

PMID- 14707242
TI  - Breathlessness in hospitalised adult patients.
AB  - Dyspnoea is defined as a sensation of difficult breathing. It is common in
      hospitalised patients and is often a harbinger of serious and potentially fatal
      pathology. The pathophysiology of dyspnoea involves complex interactions between
      peripheral and central receptors and cognition. Given the myriad causes of
      dyspnoea, a systematic approach to diagnosis is important. A good history and
      systemic examination are necessary as it is important to quickly identify the
      cause and treat it promptly. Investigations are numerous but chest radiography
      and electrocardiography are among the commonest and most useful. It is important
      to understand the mechanisms underlying dyspnoea to treat breathless patients
      successfully.

PMID- 14707244
TI  - Palmar striated xanthomas.

PMID- 14707243
TI  - Image guided navigation system-a new technology for complex endoscopic endonasal
      surgery.
AB  - PURPOSE: Endoscopic endonasal surgery (EES) has become the standard practice in
      sinonasal and anterior skull base surgery. The purpose of this manuscript is to
      describe experience using a new technology-the image guided navigation system
      (IGNS)-in complex cases undergoing EES. The advantages and disadvantages of
      computer aided surgery are discussed. PATIENTS AND METHODS: A total of 165
      endoscopic endonasal procedures were performed between April 2001 and January
      2003. IGNS was used in 34 patients in whom it was assumed that the ability to
      identify surgical sites accurately could be compromised by previous surgery,
      massive recurrent polyposis, or abnormal anatomy, or when biopsies had to be
      taken from specific anatomic locations (for example, clivus, wall of sphenoid
      sinus, orbital apex). The precision of the navigation system, total operating
      room time, surgeon's satisfaction and confidence, and intraoperative and
      postoperative complications were recorded. RESULTS: In 33 out of 34 patients the
      surgical procedure was uneventful. One patient with an atelectatic maxillary
      sinus developed a minor complication of preseptal orbital haematoma. In 94% the
      IGNS provided accurate anatomical localisation with less than 2 mm localisation
      error (1.1-2.0 mm, mean 1.6 mm). In all cases the surgical team felt that the
      system increased the intraoperative safety factor for the patient. The overall
      operating room time at the end of the study was 15 minutes longer than when
      regular EES was used. CONCLUSIONS: IGNS enables a new level of efficiency and
      safety in EES. Nevertheless, it is not advised for surgeons who are not familiar
      with regular EES. For the experienced endoscopist, however, IGNS is a valuable
      new tool in complex procedures.

PMID- 14707241
TI  - Dr William Coley and tumour regression: a place in history or in the future.
AB  - Spontaneous tumour regression has followed bacterial, fungal, viral, and
      protozoal infections. This phenomenon inspired the development of numerous
      rudimentary cancer immunotherapies, with a history spanning thousands of years.
      Coley took advantage of this natural phenomenon, developing a killed bacterial
      vaccine for cancer in the late 1800s. He observed that inducing a fever was
      crucial for tumour regression. Unfortunately, at the present time little credence
      is given to the febrile response in fighting infections-no less cancer. Rapidly
      growing tumours contain large numbers of leucocytes. These cells play a part in
      both defence and repair; however, reparative functions can also support tumour
      growth. Intratumoural infections may reactivate defensive functions, causing
      tumour regression. Can it be a coincidence that this method of immunotherapy has
      been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's
      approach to cancer treatment has a place in the past, present, and future. It
      offers a rare opportunity for the development of a broadly applicable, relatively
      inexpensive, yet effective treatment for cancer. Even in cases beyond the reach
      of conventional therapy, there is hope.

PMID- 14707245
TI  - Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas
      aeruginosa in the HAART era.
AB  - Antibiotic resistance profiles are useful in directing therapeutic strategies
      during bacterial infections. Patterns of antimicrobial resistance in
      Streptococcus pneumoniae and Pseudomonas aeruginosa associated pneumonia were
      investigated in an HIV-1 infected cohort during the era of highly active
      antiretroviral therapy. The median CD4 count at presentation was significantly
      lower for cases of P aeruginosa than for S pneumoniae. However, the number of
      antibiotic resistant cases of P aeruginosa decreased throughout the study period,
      while the incidence of S pneumoniae remained unchanged. In contrast to
      pneumococcal pneumonia, we show that antiretrovirals have protected from
      pneumonia due to antibiotic resistant P aeruginosa. These findings have
      implications for the treatment of individuals presenting with serious infections
      in which antibiotic therapy needs to be instituted before identification and
      sensitivities are known.

PMID- 14707247
TI  - The stethoscope: some preliminary investigations.
AB  - Textbooks, clinicians, and medical teachers differ as to whether the stethoscope
      bell or diaphragm should be used for auscultating respiratory sounds at the chest
      wall. Logic and our results suggest that stethoscope diaphragms are more
      appropriate.

PMID- 14707248
TI  - A physiotherapy specialist clinic in paediatric orthopaedics: is it effective?
AB  - A physiotherapy specialist clinic was set up to reduce waiting times for non
      urgent, new paediatric orthopaedic referrals. The outcome was reviewed at a
      minimum of 12 months for 1046 referrals assessed in the physiotherapy support
      clinic to analyse its effectiveness. Altogether 114 patients failed to attend the
      clinic. The remaining 932 patients form the basis of this study. Ninety three
      percent of these patients were managed without direct consultant intervention-72%
      with advice and reassurance, 17% by referral to the physiotherapy department, and
      4% with surgical appliances. Only 7% needed consultant evaluation. Median waiting
      time for non-urgent conditions was reduced from 72 weeks in May 1996 to five
      weeks in May 1999. A majority of the parents were satisfied with the clinic. The
      clinic was found to be cost effective. The success of the clinic was attributable
      to good cooperation between the consultant and physiotherapist and a well defined
      protocol for assessment and management of patients.

PMID- 14707249
TI  - Phenytoin and carbamazepine cross reactivity: report of a case and review of
      literature.
AB  - Cross reactivity between phenytoin, carbamazepine, and oxcarbazepine is reported.
      An 8 year old boy with partial seizures developed maculopapular rashes with
      itching on day 15 of carbamazepine therapy. After stopping carbamazepine,
      phenytoin 100 mg daily was prescribed two days later. On the 12th day of
      phenytoin therapy he developed cervical and axillary lymphadenopathy with fever.
      Lymph nodes revealed reactive hyperplasia. Oxcarbazepine 75 mg twice daily also
      resulted in oral and mucosa ulceration. The seizures were controlled without any
      side effects with sodium valproate 200 mg three times a day and gabapentin 300 mg
      twice a day. Due to the cross reactivity of aromatic anticonvulsants (phenytoin,
      carbamazepine, and oxcarbazepine), valproate or newer anticonvulsants should be
      used if a patient has sensitivity to these drugs.

PMID- 14707250
TI  - An unusual cause for a colonic stricture: a case of Mycobacterium xenopi
      mimicking malignancy.
AB  - Colonic strictures are very common and are a frequent finding on double contrast
      barium examination; they very often reflect the presence of malignancy,
      diverticular disease, ischaemia, inflammatory bowel disease, and rarely
      mycobacterial disease. A case of mycobacterial disease mimicking malignancy is
      presented; this was due to a rare mycobacterial subtype and there was complete
      resolution of symptoms with antimycobacterial therapy.

PMID- 14707251
TI  - Gastrointestinal stromal tumour in an inguinal hernial sac: an unusual
      presentation.
AB  - Malignancy involving hernial sacs is rare. A 72 year old man is reported who had
      a right inguinal irreducible mass as an initial presentation of gastrointestinal
      stromal tumour mimicking irreducible inguinal hernia. The diagnosis was missed at
      the time of surgery and was revealed only by the histology results of the excised
      sac.

PMID- 14707254
TI  - Proptosis in an asthmatic patient.

PMID- 14707253
TI  - Abdominal pain and vomiting in an elderly diabetic woman.

PMID- 14707255
TI  - Rheumatoid arthritis and neck pain.

PMID- 14707260
TI  - Update on irritable bowel syndrome.

PMID- 14707262
TI  - A proteomic approach for the analysis of instantly released wound and immune
      proteins in Drosophila melanogaster hemolymph.
AB  - Insects respond to microbial infection by the rapid and transient expression of
      several genes encoding antibacterial peptides. In this paper we describe a
      powerful technique, two-dimensional difference gel electrophoresis, that, when
      combined with mass spectrometry, can be used to study the immune response of
      Drosophila melanogaster at the protein level. By comparatively analyzing the
      hemolymph proteome of 2,000 third-instar Drosophila larvae, we identified 10
      differential proteins that appear in the fruit fly hemolymph very early after an
      immune-challenge with lipopolysaccharides. These proteins can be assigned to the
      immune response, because they are not induced after sterile injury. Reduction of
      integral variability or quantification problems related to conventional two
      dimensional electrophoresis and improvement of image analysis were achieved by
      the use of two fluorescent dyes to label the two different protein samples. Some
      of the immune-induced proteins, such as thioester-containing protein 2, can be
      assigned to specific aspects of the immune response; others were already reported
      as being involved in stress response. An immune-induced protein (CG18594) is
      homologous to a mammalian serine protease inhibitor that mediates the mitogen
      activated protein kinase and the NF-kappa B signaling pathways. In addition, a
      number of proteins that had not been associated with the immune response before
      were isolated and identified, and some of these were still present in the
      hemolymph 4 h after injury. Determining the function of all of these immune
      induced proteins represents an exciting challenge for increasing our knowledge of
      insect immunity.

PMID- 14707263
TI  - Nonrandom HIV-1 infection and double infection via direct and cell-mediated
      pathways.
AB  - Cells infected with two related retroviruses can generate heterozygous virions,
      which are the precursors of recombinant proviruses. Although many studies have
      focused on the frequencies and mechanisms of retroviral recombination, little is
      known about the dynamics of double infection. To examine this issue, viruses
      generated from two HIV-1 vectors containing different markers were mixed
      together, and were used to infect target cells. The numbers of cells expressing
      none, one, or both markers were measured and were used to calculate whether
      double infection occurred at frequencies expected from random infection events.
      We found that double infection occurred significantly more frequently than
      predicted from random distribution; increased rates of double infection were
      observed in both a T cell line and primary activated CD4(+) T cells. In addition
      to direct virus infection, we also examined the nature of cell-mediated HIV-1
      double infection. Increased double infection was observed in all experiments
      regardless of whether a cell line or primary human dendritic cells were used for
      capture and transmission of HIV-1. Therefore, our results indicate that HIV-1
      double infection occurs more frequently than it would at random in both direct
      and cell-mediated HIV-1 infections. To our knowledge, this is the first direct
      evidence of nonrandom double infection in HIV-1. Frequent double HIV-1 infections
      in infected individuals would allow the generation of recombinant viruses that
      could then affect their pathogenesis and evolution.

PMID- 14707264
TI  - Cyclooxygenase 2-derived prostaglandin E2 regulates the angiogenic switch.

PMID- 14707265
TI  - A myristoyl switch regulates membrane binding of HIV-1 Gag.

PMID- 14707266
TI  - DNA-dependent protein kinase inhibitors as drug candidates for the treatment of
      cancer.
AB  - Cancer presents a difficult challenge for oncologists, as there are few therapies
      that specifically target disease cells. Existing treatment strategies rely
      heavily on physical and chemical agents that nonspecifically affect DNA
      metabolism. To improve the effectiveness of these treatments, we have identified
      a new class of protein kinase inhibitor that targets a major DNA repair pathway.
      A representative of this class, 1-(2-hydroxy-4-morpholin-4-yl-phenyl)-ethanone,
      inhibits the DNA-dependent protein kinase (DNA-PK) and differs significantly from
      previously studied DNA-PK inhibitors both structurally and functionally. DNA-PK
      participates in the cellular response to and repair of chromosomal DNA double
      strand breaks (DSBs). These new selective inhibitors recapitulate the phenotype
      of DNA-PK defective cell lines including those from SCID mice. These compounds
      directly inhibit the repair of DNA DSBs and consequently enhance the cytotoxicity
      of physical and chemical agents that induce DSBs but not other DNA lesions. In
      contrast to previously studied DNA-PK inhibitors, these compounds appear benign,
      exhibiting no toxic effects in the absence of DSB-inducing treatments. Most
      importantly, 1-(2-hydroxy-4-morpholin-4-yl-phenyl)-ethanone synergistically
      enhances radiation-induced tumor control in a mouse-human xenograft assay. These
      studies validate DNA-PK as a cancer drug target and suggest a new approach for
      enhancing the effects of existing cancer therapies.

PMID- 14707267
TI  - Induction of CYP1A1 in tumor cells by the antitumor agent 2-[4-amino-3
      methylphenyl]-5-fluoro-benzothiazole: a potential surrogate marker for patient
      sensitivity.
AB  - A candidate antitumor agent, 2-(4-amino-3-methylphenyl)-5-fluoro-benzothiazole
      (5F-203), like its non-fluorinated parent compound (DF-203), has a unique
      cytotoxicity pattern in the National Cancer Institute in vitro anticancer drug
      screen. These compounds show selective toxicity for a subset of cell types
      including estrogen receptor positive breast cancer and certain renal and ovarian
      cancer cell lines. Metabolic activation of these benzothiazoles seems to be
      mediated through the CYP1 family of cytochrome P450s. In an effort to
      characterize the involvement of CYP1A1 and CYP1B1 in the unique toxicity response
      of 5F-203, constitutive and 5F-203-induced gene expression patterns were measured
      in 60 cell lines of the National Cancer Institute drug screen using TaqMan real
      time PCR. The patterns of CYP1A1 and CYP1B1 gene expression in the 60 cell lines
      were correlated with the toxicity pattern of 5F-203 and DF-203. There was
      significant correlation between drug sensitivity and induced CYP1A1 (R = 0.752, P
      < 0.001), but not constitutive CYP1A1 mRNA expression. CYP1A1 protein expression
      was found to mirror the corresponding gene expression, indicating that gene
      expression changes were concordant with function. Treatment of sensitive cell
      lines with 10 micro M resveratrol, an inhibitor of CYP1A1 induction, in
      combination with either 1 or 10 micro M 5F-203 showed an ablation of the observed
      CYP1A1, but not CYP1B1 mRNA induction in parallel with a decreased sensitivity to
      5F-203. Fine needle aspirates were obtained from a variety of human tumor
      xenografts, and treated ex vivo with 1 micro M 5F-203 for 24 h. In these samples,
      induction of CYP1A1 by 5F-203 correlated with in vitro sensitivity (R = 0.711, P
      < 0.05), and corresponded to in vivo sensitivity in human tumor xenografts. These
      data are concordant with the idea that toxicity of 5F-203 requires activation by
      CYP1A1, and therefore induction of CYP1A1 mRNA in response to 5F-203 treatments
      ex vivo may provide a possible surrogate marker for determination of drug
      sensitive tumors in patients.

PMID- 14707269
TI  - Nitric oxide does not mediate but inhibits transformation and tumor phenotype.
AB  - Although inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are
      implicated in tumor pathology, their role in the early stages of carcinogenesis
      is not well defined. Tumor necrosis factor alpha (TNFalpha) induces iNOS and NO
      production in transformation-sensitive JB6 P+, but not in transformation
      resistant JB6 P-, mouse epidermal cells. We tested the hypothesis that iNOS, by
      generating NO and reactive nitrogen species, mediates tumor promoter-induced
      transformation. Specific [N-[3-(aminomethyl)benzyl]acetamidine (1400W)] and non
      specific (N(omega)-methyl-L-arginine) iNOS inhibitors significantly reduced
      TNFalpha-induced NO production in P+ cells but both iNOS inhibitors enhanced
      TNFalpha-induced anchorage-independent transformation, thus ruling out a mediator
      role and suggesting an inhibitor role for NO. Independent support for an
      inhibitor role came from the observation that the NO donor [(Z)-1-[N-(2
      aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO)] inhibited
      TNFalpha- and 12-O-tetradecanoylphorbol-13-acetate-induced transformation.
      DETA/NO treatment also suppressed tumor phenotype in tumorigenic JB6 RT101 (Tx)
      cells. Higher concentrations of DETA/NO induced apoptosis. The transformation
      inhibitory effect of lower DETA/NO concentrations may be attributable in part to
      inhibition by NO of NF-kappaB-dependent but not of AP-1-dependent transcription.
      IN CONCLUSION: (a) induction of iNOS and NO production does not mediate but
      actually prevents tumor promotion; (b) iNOS inhibitors enhance the transformation
      response, and therefore appear not to be appropriate as chemoprevention agents;
      and (c) NO has both chemopreventive and tumoricidal effects, suggesting promise
      in cancer chemoprevention and therapy.

PMID- 14707268
TI  - Simultaneous activation of the intrinsic and extrinsic pathways by histone
      deacetylase (HDAC) inhibitors and tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) synergistically induces mitochondrial damage and
      apoptosis in human leukemia cells.
AB  - Interactions between histone deacetylase (HDAC) inhibitors and tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2 ligand, were
      examined in human leukemia cells (e.g., U937, Jurkat, and HL-60). Simultaneous
      exposure of cells to 100-ng/ml TRAIL with either 1-mM sodium butyrate or 2- micro
      M suberoylanilide hydroxamic acid resulted in a striking increase in leukemic
      cell mitochondrial damage, caspase activation, and apoptosis. Lethal effects were
      significantly diminished in U937 cells ectopically expressing dominant-negative
      caspase-8, dominant-negative Fas-associated death domain, CrmA (receptor
      pathway), or Bcl-2 or Bcl-X(L) (mitochondrial pathway). Analysis of mitochondrial
      events in U937 cells exposed to TRAIL/HDAC inhibitors revealed enhanced Bid
      activation and Bax translocation, loss of mitochondrial membrane potential, and
      cytoplasmic release of cytochrome c, Smac/DIABLO, and apoptosis-inducing factor.
      No changes were observed in expression of FLICE-like inhibitory protein, TRAIL
      receptors, or reactive oxygen species generation. TRAIL/HDAC inhibitor-induced
      apoptosis triggered caspase-dependent cleavage of p21(WAF1/CIP1); moreover,
      enforced expression of a nuclear localization signal deletant form of
      p21(WAF1/CIP1) significantly diminished lethality. Lastly, p27(KIP1), pRb, X
      linked inhibitor of apoptosis, and Bcl-2 displayed extensive proteolysis. These
      findings indicate that coadministration of TRAIL with HDAC inhibitors
      synergistically induces apoptosis in human myeloid leukemia cells and provide
      further evidence that simultaneous activation of the extrinsic and intrinsic
      pathways in such cells leads to a dramatic increase in mitochondrial injury and
      activation of the caspase cascade.

PMID- 14707270
TI  - Inhibition of tumor growth by a novel approach: in situ allicin generation using
      targeted alliinase delivery.
AB  - Allicin (diallyl thiosulfinate), a highly active component in extracts of freshly
      crushed garlic, is the interaction product of non-protein amino acid alliin (S
      allyl-L-cysteine sulfoxide) with the enzyme alliinase (alliin lyase; EC 4.4.1.4).
      Allicin was shown to be toxic in various mammalian cells in a dose-dependent
      manner in vitro. We made use of this cytotoxicity to develop a novel approach to
      cancer treatment, based on site-directed generation of allicin. Alliinase from
      garlic was chemically conjugated to a mAb directed against a specific tumor
      marker, ErbB2. After the mAb-alliinase conjugate was bound to target tumor cells,
      the substrate, alliin, was added. In the presence of alliin, tumor-localized
      alliinase produced allicin, which effectively killed N87 and CB2, both ErbB2
      expressing cells in vitro, whereas 32D cells (a murine hematopoietic progenitor
      cell line, devoid of the ErbB2 receptors) were not affected. Moreover, using N87,
      a human tumor cell line xenograft in athymic nude mice, we demonstrated for the
      first time, a high antitumor activity of allicin that was produced in situ by the
      conjugate, on alliin administration in vivo, while at the same time other tissues
      were unharmed due to the inert nature of alliin and the high clearance rate of
      allicin. The effect of the treatment on tumor growth arrest became significant 2
      weeks after its onset, and it continued to rise, reaching highly significant
      inhibition a week later. Ten days after the end of the treatment (day 18), tumor
      growth inhibition was still the same.

PMID- 14707271
TI  - Suppression of microtubule dynamics by discodermolide by a novel mechanism is
      associated with mitotic arrest and inhibition of tumor cell proliferation.
AB  - Discodermolide is a new microtubule-targeted drug in Phase I clinical trials that
      inhibits tumor growth and induces G(2)-M cell cycle arrest. It is effective
      against paclitaxel-resistant cell lines and acts synergistically in combination
      with paclitaxel. Suppression of microtubule dynamics by microtubule-targeted
      drugs has been hypothesized to be responsible for their ability to inhibit
      mitotic progression and cell proliferation. To determine whether discodermolide
      blocks mitosis by an effect on microtubule dynamics, we analyzed the effects of
      discodermolide on microtubule dynamics in living A549 human lung cancer cells
      during interphase at concentrations that block mitosis and inhibit cell
      proliferation. We found that discodermolide (7-166 nM) significantly suppressed
      microtubule dynamic instability. At the IC(50) for proliferation (7 nM
      discodermolide, 72 h), overall dynamicity was reduced by 23%. The principal
      parameters of dynamic instability suppressed by discodermolide were the
      microtubule shortening rate and length shortened. In addition, discodermolide
      markedly increased the frequency of rescued catastrophes. At the discodermolide
      concentration that resulted in 50% of maximal mitotic block (83 nM, 20 h), most
      microtubules were completely non-dynamic, no anaphases occurred, and all spindles
      were abnormal. The dynamicity of the remaining dynamic microtubules was reduced
      by 62%. The results indicate that a principal mechanism of inhibition of cell
      proliferation and mitotic block by discodermolide is suppression of microtubule
      dynamics. Importantly, the results indicate significant additional stabilizing
      effects of discodermolide on microtubule dynamics as compared with those of
      paclitaxel that may in turn reflect differences in their binding sites and their
      effects on tubulin conformation.

PMID- 14707272
TI  - E1A gene therapy inhibits angiogenesis in a Ewing's sarcoma animal model.
AB  - We assessed vascular endothelial growth factor (VEGF) expression in four
      different human Ewing's sarcoma cell lines (TC71, SK-ES, RD, and A4573) and in
      tumors in nude mice induced following s.c. injection of TC71 cells. Three of the
      four cell lines (TC71, SK-ES, and A4573) expressed significantly higher levels of
      VEGF than did normal human osteoblasts. Transfection of the adenovirus type 5
      early region 1A (E1A) gene into TC71 cells down-regulated VEGF expression in
      vitro. In the mice bearing TC71 cell tumors, intratumoral injections of an
      adenoviral vector containing the E1A gene (Ad-E1A) decreased VEGF expression,
      inhibited tumor growth, and increased the survival rates in comparison with the
      mice given injections of PBS or an adenoviral vector containing beta
      galactosidase (Ad-beta-gal). E1A gene therapy also significantly reduced blood
      vessel density and induced cell apoptosis in the tumors. These results
      demonstrate that E1A gene therapy inhibits angiogenesis, most likely by
      suppression of VEGF expression. Thus, E1A gene therapy may be a new therapeutic
      approach for Ewing's sarcoma.

PMID- 14707273
TI  - Hematopoietic expression of O(6)-methylguanine DNA methyltransferase-P140K allows
      intensive treatment of human glioma xenografts with combination O(6)
      benzylguanine and 1,3-bis-(2-chloroethyl)-1-nitrosourea.
AB  - The major mechanism of tumor cell resistance to 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) is the DNA repair protein O(6)-methylguanine DNA
      methyltransferase (MGMT). This repair system can be temporarily inhibited by the
      free base O(6)-benzylguanine (BG), which depletes cellular MGMT activity and
      sensitizes tumor cells and xenografts to BCNU. In clinical studies, the
      combination of BG and BCNU enhanced the myeloid toxicity of BCNU, thereby
      reducing the maximum tolerated dose. We have shown previously that retroviral
      expression of the P140K mutant of MGMT (MGMT-P140K) in murine and human
      hematopoietic cells produces significant resistance of bone marrow cells to low
      dose, combination BG and BCNU treatment in vivo. In the current study, we
      investigated the ability of bone marrow transplantation with MGMT-P140K
      transduced hematopoietic cells to protect against an intensive antitumor
      treatment regimen of combination BG and BCNU in non-obese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. The donor marrow cells underwent in
      vivo BG and BCNU selection before transplantation, allowing infusion of a highly
      selected population of transduced cells. Tolerance to the intensive BG and BCNU
      treatment was markedly improved in secondary MGMT-P140K-transplanted mice (n =
      19) compared to untransplanted mice (n = 15), as indicated by blood counts and
      survival rate. The dose-intensified BG and BCNU therapy produced significant
      growth delays of glioma xenografts in MGMT-P140K-transplanted mice, extending the
      tumor doubling time by >40 days. These results demonstrate that MGMT-P140K
      transduced bone marrow protects against BG and BCNU combination therapy in vivo
      and allows dose-intensified treatment of tumor xenografts.

PMID- 14707274
TI  - Antitumor activity of the novel melphalan containing tripeptide J3 (L-prolyl-L
      melphalanyl-p-L-fluorophenylalanine ethyl ester): comparison with its m-L
      sarcolysin analogue P2.
AB  - Peptichemio (PTC), a mixture of six oligopeptides all containing m-L-sarcolysin,
      has previously shown impressive results in clinical trials. The tripeptide P2 (L
      prolyl-m-L-sarcolysyl-p-L-fluorophenylalanine ethyl ester) has been suggested as
      the main contributor to PTC activity. In contrast to its analogue melphalan, m-L
      sarcolysin never reached clinical use. To allow a direct comparison, the
      corresponding melphalan containing tripeptide J3 (L-prolyl-L-melphalanyl-p-L
      fluorophenylalanine ethyl ester) was synthesized and its activity was compared
      with that of P2; the activities of melphalan and m-L-sarcolysin were studied in
      parallel. Cytotoxic activity in human tumor cell lines and some fresh human tumor
      specimens were analyzed as well as effects on cellular metabolism, macromolecular
      synthesis, and preliminary evaluation of the cell death characteristics. The
      results show that melphalan and m-L-sarcolysin display similar activity in these
      systems and that the tripeptides were more active than their parent monomers.
      Surprisingly however, the melphalan containing tripeptide J3 demonstrated a
      significantly more rapid and stronger activity than the m-L-sarcolysin analogue
      P2. Finally, the in vivo toxicity and activity of melphalan and J3 were
      investigated in mice bearing human leukemia cells in s.c. fibers. The in vitro
      results seem translatable into the in vivo situation, demonstrating better
      antileukemic effect of J3 but similar side effects as melphalan.

PMID- 14707275
TI  - Targeted delivery of human pro-apoptotic enzymes to tumor cells: In vitro studies
      describing a novel class of recombinant highly cytotoxic agents.
AB  - The serine protease granzyme B (GrB, 25 kDa) can initiate apoptosis by multiple
      mechanisms including directly activating caspases, inducing DNA fragmentation,
      activating the mitochondrial death pathway, and directly cleaving the nuclear
      matrix. The purpose of this study was to determine whether a recombinant antibody
      could deliver sufficient amounts of GrB to target cells to generate an apoptotic
      signal. The gene sequence encoding GrB was attached to the single-chain anti
      melanoma antibody scFvMEL (anti-gp240) via a flexible (G(4)S) tether. The 53-kDa
      GrB/scFvMEL fusion protein was expressed in bacteria and purified by metal
      affinity chromatography. Western blotting confirmed presence of both scFvMEL and
      GrB proteins. The fusion construct displayed intact GrB enzymatic activity
      (specific activity = 2.6 x 10(5) units/ micro mol) similar to native GrB
      (specific activity = 4.8 x 10(5) units/ micro mol). The construct bound
      specifically to human A375-M melanoma cells and delivered GrB to the cytosol as
      assessed by confocal microscopy. Against log-phase melanoma cells, GrB/scFvMEL
      demonstrated an IC(50) of 20 nM and minimal cytotoxicity to non-target cells at
      doses of up to 1 micro M. Coadministration of exogenous perforin (PFN) to cells
      resulted in a slight increase in the cytotoxic effects of the GrB/scFvMEL
      construct on A375 target cells and a significant increase in cytotoxicity to
      SKBR3 (non-target) cells. The cytotoxic effects of this fusion construct on
      target cells were similar to those of the previously described MEL sFv/rGel
      fusion toxin (IC(50) approximately 20 nM). The construct produced impressive
      apoptotic effects by 8 h after treatment of target cells. Mediation of the
      apoptotic effects of GrB/scFvMEL included caspase-3 cleavage and release of
      cytochrome c into the cytosolic compartment from the mitochondrial compartment.
      These studies demonstrate that delivery of the human pro-apoptotic pathway enzyme
      GrB to tumor cells may have significant therapeutic potential for cancer
      treatment and represents a new class of targeted therapeutic agents with a
      defined mechanism of action.

PMID- 14707276
TI  - Genetic polymorphism at the 5' regulatory region of multidrug resistance 1 (MDR1)
      and its association with interindividual variation of expression level in the
      colon.
AB  - The multidrug resistance 1 (MDR1) is a key molecule in determining not only the
      resistance of cancer cells to anticancer agents but also the disposition of a
      variety of drugs in intestinal and other tissues. However, the mechanism
      underlying interindividual variations in levels of MDR1 activity and expression
      in various tissues remains unclear. We analyzed the nucleotide sequence
      polymorphisms in the 5' upstream regulatory region of the gene spanning 4 kb from
      the transcriptional start site of MDR1 and tried to identify any associations
      between polymorphisms and MDR1 expression. Within that region, we identified
      eight single nucleotide polymorphisms (SNPs) in the region in the Japanese
      population. Of the SNPs identified, -2410T>C, -1910T>C, and 692T>C were in
      perfect linkage disequilibrium. In normal colorectal mucosa, diplotypes at the
      region showed more significant association with the expression level of MDR1 mRNA
      than each SNP did. In an in vitro reporter assay, transcription activity of the
      minor-type construct carrying haplotypes 2 and 3 was significantly lower than
      that of the major-type construct carrying haplotype 1. We next identified two DNA
      binding proteins: one protein bound to the nucleotide sequence carrying -692T but
      not to that carrying -692C and another bound to the nucleotide sequence carrying 
      2352G but three times weaker than that carrying -2352A. This suggested the
      significance of SNP at -692 and -2352 of MDR1 in variable expression in the colon
      interindividually. This is the first report connecting SNPs and interindividual
      variety of MDR1 expression rationally.

PMID- 14707277
TI  - Genistein sensitizes diffuse large cell lymphoma to CHOP (cyclophosphamide,
      doxorubicin, vincristine, prednisone) chemotherapy.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) has been increasing and is now the
      leading cause of death in males aged 15-54. Diffuse large cell lymphoma (DLCL) is
      the most common subtype of NHL. These cells are notable for the high expression
      of the transcription factor nuclear factor kappa beta (NF-kappaB), raising the
      possibility that constitutive activation of the NF-kappaB pathway may contribute
      to the poor prognosis of DLCL patients. Soy isoflavone genistein promotes
      apoptosis by decreasing NF-kappaB activity. The combination of cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) remains the standard therapy for
      DLCL with a cure rate of approximately 40%. The WSU-DLCL(2) cell line and its
      severe combined immunodeficient (SCID) xenograft have constitutively active NF
      kappaB which provides us with an excellent model in which to study NF-kappaB
      modulation and CHOP sensitization by genistein. The antitumor activity of CHOP
      with or without a genistein was evaluated in our WSU-DLCL(2) model. In vivo, WSU
      DLCL(2)-bearing SCID mice received genistein alone (800 micro g kg(-1) day(-1),
      p.o. as gavages for 5 days), CHOP alone ("C", 40 mg/kg, i.v.; "H", 3.3 mg/kg,
      i.v.; "O", 0.5 mg/kg, i.v.; and "P", 0.2 mg/kg, every day for 5 days, p.o.), or
      genistein for 5 days followed by CHOP. Tumor growth inhibition (T/C), tumor
      growth delay (T - C), and log(10) kill for genistein, CHOP, and genistein
      followed by CHOP were 33.6%, 19.2%, and 5.2%; 7, 8, and 17 days; and 1.0, 1.2,
      and 2.6, respectively. To begin elucidating the mechanism of genistein-induced
      sensitization of WSU-DLCL(2) cells to CHOP chemotherapy in this xenograft mouse
      model, we studied the in vitro effect of genistein on WSU-DLCL(2) growth
      inhibition, cell cycle, Bax:Bcl-2 ratio, NF-kappaB DNA binding, and apoptosis in
      vitro. At 30 micro M, genistein inhibited the growth significantly, induced G(2)
      M arrest, increased Bax:Bcl-2 ratio, decreased NF-kappaB DNA binding, and induced
      apoptosis. Genistein also inhibited NF-kappaB DNA binding in vivo, whereas CHOP
      enhanced it. Our results show that genistein has growth modulatory effects on WSU
      DLCL(2) cells and enhances the antitumor activity of CHOP. Because soy isoflavone
      genistein is a widely available nutritional supplement, its use in combination
      with CHOP chemotherapy should be further explored in a clinical trial in patients
      with NHL.

PMID- 14707278
TI  - Phosphoproteomic fingerprinting of epidermal growth factor signaling and
      anticancer drug action in human tumor cells.
AB  - Many proteins regulating cancer cell growth are tyrosine phosphorylated. Using
      antiphosphotyrosine affinity chromatography, thiourea protein solubilization, two
      dimensional PAGE, and mass spectrometry, we report here the characterization of
      the epidermal growth factor (EGF)-induced phosphoproteome in A431 human
      epidermoid carcinoma cells. Using this approach, more than 50 distinct tyrosine
      phosphoproteins are identifiable within five main clusters-cytoskeletal proteins,
      signaling enzymes, SH2-containing adaptors, chaperones, and focal adhesion
      proteins. Comparison of the phosphoproteomes induced in vitro by transforming
      growth factor-alpha and platelet-derived growth factor demonstrates the pathway-
      and cell-specific nature of the phosphoproteomes induced. Elimination of both
      basal and ligand-dependent phosphoproteins by cell exposure to the EGF receptor
      catalytic inhibitor gefitinib (Iressa, ZD1839) suggests either an autocrine
      growth loop or the presence of a second inhibited kinase in A431 cells. By
      identifying distinct patterns of phosphorylation involving novel signaling
      substrates, and by clarifying the mechanism of action of anticancer drugs, these
      findings illustrate the potential of immunoaffinity-based phosphoproteomics for
      guiding the discovery of new drug targets and the rational utilization of pathway
      specific chemotherapies.

PMID- 14707282
TI  - MDM2, an introduction.
AB  - The murine double minute 2 (mdm2) gene encodes a negative regulator of the p53
      tumor suppressor. Amplification of mdm2 or increased expression by unknown
      mechanisms occurs in many tumors. Thus, increased levels of MDM2 would inactivate
      the apoptotic and cell cycle arrest functions of p53, as do deletion or mutation
      of p53, common events in the genesis of many kinds of tumors. MDM2 functions as
      an E3 ubiquitin ligase to degrade p53. MDM2 also binds another tumor suppressor,
      ARF. This interaction sequesters MDM2 in the nucleolus away from p53, thus
      activating p53. Many additional MDM2 interacting proteins have been identified.
      Functions of MDM2 independent of p53 have also been identified. This article is
      an introduction to MDM2, its structure and biological functions, as well as its
      relationship to its binding partners.

PMID- 14707283
TI  - The MDM2-p53 interaction.
AB  - Activation of the p53 protein protects the organism against the propagation of
      cells that carry damaged DNA with potentially oncogenic mutations. MDM2, a p53
      specific E3 ubiquitin ligase, is the principal cellular antagonist of p53, acting
      to limit the p53 growth-suppressive function in unstressed cells. In unstressed
      cells, MDM2 constantly monoubiquitinates p53 and thus is the critical step in
      mediating its degradation by nuclear and cytoplasmic proteasomes. The interaction
      between p53 and MDM2 is conformation-based and is tightly regulated on multiple
      levels. Disruption of the p53-MDM2 complex by multiple routes is the pivotal
      event for p53 activation, leading to p53 induction and its biological response.
      Because the p53-MDM2 interaction is structurally and biologically well
      understood, the design of small lipophilic molecules that disrupt or prevent it
      has become an important target for cancer therapy.

PMID- 14707284
TI  - Cell cycle regulatory functions of the human oncoprotein MDM2.
AB  - The protein (MDM2) coded by the mouse double minute-2 (mdm2) gene or its human
      homologue is well known as an oncoprotein. Malignant human tumors particularly
      breast tumors and soft tissue sarcomas frequently overexpress MDM2. Artificial
      amplification of mdm2 gene derived from a transformed murine cell line enhances
      tumorigenic potential of murine cells. Consistent with its tumorigenic property,
      mouse or human MDM2 can inactivate several functions of the tumor suppressor p53
      and can degrade p53. The protein also interacts with other tumor suppressors, and
      these interactions may contribute to its tumorigenic property. In spite of its
      oncogenic role, mouse or human MDM2 induces G(1) arrest in normal human or murine
      cells. Some cell lines bearing known genetic mutations are insensitive to MDM2
      mediated growth arrest. This review is aimed to collect available information on
      the functions of MDM2 that could potentially regulate cell cycle and to discuss
      how this information may fit in one model that could explain the two apparently
      opposite G(1) arrest and oncogenic function of MDM2.

PMID- 14707285
TI  - Posttranslational modification of MDM2.
AB  - The functions of the MDM2 protein, in particular its E3 ubiquitin ligase activity
      and its ability to interact with a number of cellular proteins intimately
      involved in growth regulation, are modulated by sumoylation and multisite
      phosphorylation. These posttranslational mechanisms not only regulate the
      intrinsic activity of MDM2 in response to cellular stresses, but also govern its
      subcellular localization, differentiate between MDM2-mediated ubiquitination of
      p53 and autoubiquitination, integrate the stress response with mechanisms that
      mediate cell survival, and modulate the interaction of MDM2 with cellular and
      viral proteins. In this review, we summarize our current knowledge of the role of
      posttranslational modifications of MDM2 and their functional relevance.

PMID- 14707286
TI  - p53-independent functions of MDM2.
AB  - The tumor suppressor p53 is inactivated by overexpression of MDM2 in about 10% of
      human tumors. However, p53 is inactivated by other mechanisms in the majority of
      tumors, raising the possibility that MDM2 may be irrelevant to transformation in
      most cases. However, MDM2 has been reported to have p53-independent functions, in
      cell cycle control, differentiation, cell fate determination, DNA repair, basal
      transcription, and other processes. Furthermore, MDM2 appears to contribute to
      the transformed phenotype in the absence of wild-type p53. Nevertheless, the
      number of studies is still limited, and the evidence in some cases does not
      unequivocally show that the functions are p53 independent. We will discuss the
      circuits of regulation involving MDM2 that do not directly concern p53.
      Hopefully, future work will consolidate our understanding of the p53-independent
      pathological functions of MDM2 and will lead to useful therapeutic interventions
      that target the majority of tumors.

PMID- 14707287
TI  - Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and
      mdm2 to inhibit prostate cancer progression and prolong survival.
AB  - Loss of heterozygosity or mutation at the p53 tumor suppressor gene locus is
      frequently associated with advanced human prostate cancer. Hence, replacement p53
      gene therapy may prove to be efficacious for this disease. While many mutations
      result in p53 molecules with oncogenic properties, other variants may possess
      wild-type properties with increased tumor suppressor activity. We have chosen to
      investigate the activity of a naturally occurring variant p53 molecule,
      p53(R172L), carrying an arginine-to-leucine mutation at codon 172. We demonstrate
      that p53(R172L) can differentially activate expression of genes involved in cell
      cycle control and apoptosis in vitro. Transgenic mice expressing a
      subphysiological level of a p53(R172L) minigene (PB-p53(R172L)) in the prostate
      epithelium were generated and bred to the transgenic adenocarcinoma mouse
      prostate (TRAMP) model of prostate cancer. While PB-p53(R172L) transgenic mice
      developed normally with no detectable prostate gland phenotype, we observed a
      significant increase in the apoptotic index in the prostate glands of TRAMP x PB
      p53(R172L) F1 mice. We noted an increase in the expression of Bax in the bigenic
      mice concomitant with the reduced incidence and rate of tumor growth and
      increased survival. While low-level expression of the p53(R172L) variant had no
      obvious influence on normal prostate tissue, it was able to significantly inhibit
      prostate cancer progression in the context of a genetically predisposed model
      system. This suggests that additional tumor-related events specifically influence
      the ability of the variant p53(R172L) molecule to inhibit tumor growth. These
      studies support gene therapy strategies employing specific p53 variants.

PMID- 14707288
TI  - Multiple response elements and differential p53 binding control Perp expression
      during apoptosis.
AB  - The p53 tumor suppressor gene responds to cellular stress by activating either
      cell cycle arrest or apoptosis. A growing number of target genes involved in each
      of these pathways have been identified. However, the mechanism by which the
      apoptosis versus arrest decision is made remains to be elucidated. Perp is a
      proapoptotic target gene of p53 expressed to high levels in apoptotic cells
      compared with those undergoing cell cycle arrest. This pattern of expression is
      unusual among p53 target genes, many of which are induced to similar levels
      during arrest and apoptosis. Here, we describe the regulation of the Perp gene by
      p53 through at least three response elements in the Perp promoter and first
      intron. These sites are occupied in vivo in E1A-expressing mouse embryo
      fibroblasts undergoing apoptosis but not cell cycle arrest, in contrast to the
      p21 5' response element, which is occupied during both. The apoptosis-deficient
      p53 point mutant, p53V143A, displays a selective deficit in binding to the Perp
      elements, demonstrating that p53 can distinguish between Perp and p21 at the
      level of DNA binding. These results provide mechanistic insight into the
      selective expression of Perp during apoptosis and may provide a useful model for
      studying the p53-dependent cell cycle arrest versus apoptosis decision.

PMID- 14707289
TI  - Telomere instability in a human tumor cell line expressing NBS1 with mutations at
      sites phosphorylated by ATM.
AB  - Nijmegen breakage syndrome (NBS) is an autosomal genetic disease demonstrating a
      variety of phenotypic abnormalities, including premature aging, increased cancer
      incidence, chromosome instability, and sensitivity to ionizing radiation. The
      gene involved in NBS, NBS1, is part of the MRE11/RAD50/NBS1 (MRN) complex that
      also includes MRE11 and RAD50, which is involved in DNA repair and cell cycle
      regulation in response to DNA damage. The MRN complex is also involved in
      telomere maintenance, as demonstrated by the shortened telomeres in NBS primary
      human fibroblasts and the association of NBS1 with the telomere-binding protein
      TRF2. To learn more about how a deficiency in telomere maintenance might
      contribute to chromosome instability in NBS, we have investigated the stability
      of telomeres in two telomerase-positive human tumor cell clones, BNmt-On and BNmt
      Off, expressing an inducible NBS1(S278A/S343A) gene containing mutations at
      serines 278 and 343 phosphorylated by ATM. The results demonstrate an increased
      rate of telomere loss in both clones following expression of NBS1(S278A/S343A).
      The absence of detectable changes in average telomere length suggests that NBS1
      associated telomere loss results from stochastic events involving complete
      telomere loss or loss of telomere capping function. The recombination events
      associated with telomere loss were found to be similar to those shown previously
      to result in breakage/fusion/bridge cycles, suggesting that telomere loss can
      contribute to chromosome instability in NBS1-deficient cells. Telomere loss
      showed no correlation with radiosensitivity or radioresistant DNA synthesis,
      demonstrating that NBS1(S278A/S343A) promotes telomere loss through a separate
      pathway from these other phenotypes associated with NBS.

PMID- 14707290
TI  - Ligand binding up-regulates EphA2 messenger RNA through the mitogen-activated
      protein/extracellular signal-regulated kinase pathway.
AB  - The EphA2 receptor tyrosine kinase is overexpressed in aggressive cancer cells,
      where it critically influences many aspects of malignant character. Although high
      levels of EphA2 have been documented in many different cancers, relatively little
      is known of the mechanisms that govern EphA2 gene expression in normal or
      malignant cells. Our present studies demonstrate that EphA2 influences the
      regulation of its own gene expression. Specifically, ligand-mediated
      phosphorylation of EphA2 transmits signals to the nucleus via extracellular
      signal-regulated kinase kinases to up-regulate de novo EphA2 gene expression and
      synthesis. This mechanism governs EphA2 expression in normal and malignant cells.
      In normal cells, EphA2 protein expression is balanced by ligand-mediated
      induction of EphA2 gene expression countered by EphA2 protein turnover. These
      findings suggest that EphA2 expression and ligand binding are intimately linked
      in epithelial cells. Increased understanding of this mechanism could have
      important implications for understanding the causes of EphA2 overexpression and
      for developing new strategies for therapeutic intervention in the many cancers
      that overexpress EphA2.

PMID- 14707291
TI  - Essential role of Raf in Ras transformation and deregulation of matrix
      metalloproteinase expression in ovarian epithelial cells.
AB  - Oncogenic Ras mediates its actions through activation of multiple downstream
      effector signaling cascades, which in turn regulate transcription factor
      activation and cause changes in gene expression. However, there exist striking
      cell type differences in effector pathways that are activated by Ras, in which
      effectors are sufficient or necessary to promote Ras oncogenesis, and in the gene
      targets of Ras transformation. Therefore, we evaluated the contribution of
      specific effectors in mediating H-Ras(12V) transformation of rat ovarian surface
      epithelial (ROSE) cells and up-regulation of matrix metalloproteinase (MMP) gene
      expression. First, we found that Raf activation alone was sufficient to partially
      reconstitute H-Ras(12V)-mediated morphological and growth transformation.
      However, Raf-independent signaling pathways are required for full Ras
      transformation of ROSE cells. Ras transformation did not cause activation of the
      phosphatidylinositol 3-kinase (PI3K) target, Akt, and PI3K inhibition did not
      reverse morphological transformation but did inhibit growth in soft agar,
      indicating a role for basal PI3K activity in anchorage-independent growth.
      Second, we determined that MMP-3 and MMP-10, but surprisingly not MMP-9, gene
      expression was up-regulated in Ras-transformed ROSE cells. Raf activation alone
      was fully sufficient and necessary for MMP transcriptional up-regulation.
      However, up-regulation of MMP-3 or MMP-10 gene expression alone is not critical
      for Ras-mediated transformation. In summary, in contrast to other epithelial cell
      types, Raf is a major effector for Ras transformation of ovarian epithelial
      cells.

PMID- 14707293
TI  - Contribution of cerebral amyloid angiopathy to Alzheimer's disease.

PMID- 14707295
TI  - Cognitive profiles in Alzheimer's disease.

PMID- 14707296
TI  - Depressive symptoms and cognitive decline--disentangling the effect of affect.

PMID- 14707297
TI  - Functional magnetic resonance imaging.
AB  - Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging
      (fMRI) is a powerful approach to defining activity in the healthy and diseased
      human brain. BOLD fMRI detects local increases in relative blood oxygenation that
      are most probably a direct consequence of neurotransmitter action and thus
      reflect local neuronal signalling. The method allows localisation to volumes of
      the order of a few to several cubic millimetres and can be used in serial studies
      of individual subjects. Basic approaches to experimental design and analysis are
      reviewed briefly, as well as potential clinical applications. The latter include
      three broad areas: anatomical characterisation of normal or pathological patterns
      of brain functioning; distinguishing pathological traits; and monitoring
      treatment responses. New research is emphasising the integration of fMRI with
      other techniques, particularly electrophysiological. In conjunction with MRI
      methods for characterising pathological load, fMRI promises a refined
      understanding of when disease processes begin and how they can be modified by new
      treatments.

PMID- 14707298
TI  - Hemispatial neglect.
AB  - The syndrome of hemispatial neglect is characterised by reduced awareness of
      stimuli on one side of space, even though there may be no sensory loss. Although
      it is extremely common, it has proven to be a challenging condition to
      understand, and to treat. New insights from detailed behavioural and anatomical
      studies in patients, as well as functional imaging in healthy individuals, have
      begun to reveal some of the component deficits underlying the disorder. This
      review focuses on important clinical issues in neglect, including bedside
      diagnostic tests and emerging therapeutic and rehabilitation methods, involving
      both behavioural and drug treatments.

PMID- 14707300
TI  - Vertebrobasilar dolichoectasia diagnosed by magnetic resonance angiography and
      risk of stroke and death: a cohort study.
AB  - OBJECTIVE: There are only limited epidemiological studies evaluating the
      association between vertebrobasilar dolichoectasia (VBD) and outcomes. This study
      was designed to elucidate the outcome and prognosis of adults diagnosed with VBD
      by magnetic resonance angiography (MRA) and to ascertain if these outcomes were
      independent of known vascular risk factors. METHODS: A cohort study was designed
      to compare VBD cases identified retrospectively from a computerised database of
      MRA reports with age and sex matched controls evaluated after a 4-7 year period,
      and 1440 MRA reports were reviewed. The inclusion criteria were age > or =18
      years and a radiological diagnosis of VBD. Patients were excluded if there was
      haemodynamically significant stenosis or occlusion of the posterior circulation.
      Data were obtained by medical record review and telephone questionnaires. The
      primary outcome measure was transient or fixed posterior circulation dysfunction
      (PCD), with a secondary outcome measure of all cause mortality. RESULTS: Sixty
      four VBD cases were obtained, and 19 cases (30%) were excluded due to refusal
      and/or insufficient follow up data. From the same computerised database, 45
      controls were selected by consecutive sampling. The mean age at follow up was
      73.4 years for VBD cases and 73.1 years for controls, with a median follow up
      period of 64 months. VBD was associated with fixed/transient PCD (p = 0.0001;
      estimated adjusted odds ratio (OR) of 20.6 and confidence interval (CI) of 4.4 to
      95.3), and with all cause mortality (OR = 3.6 CI 1.3 to 10.3); (p = 0.018). VBD
      cases had 36% mortality, with 50% occurring within 34 months of the initial
      diagnosis. The VBD cumulative survival curve was statistically different from the
      controls (p = 0.012 by Mantel-Cox log rank test). CONCLUSIONS: This study
      suggests that VBD may be an independent risk factor for stroke. VBD cases had an
      increased likelihood for PCD, all cause mortality, and reduced cumulative
      survival independent of other vascular risk factors in this cohort. Larger
      population based prospective studies are required to verify these results.

PMID- 14707302
TI  - Paul Broca's thermometric crown.

PMID- 14707301
TI  - Dolichoectatic arterial compression of the anterior visual pathways: neuro
      ophthalmic features and clinical course.
AB  - AIM: To characterise the clinical findings and natural history of anterior visual
      pathway compression by dolichoectatic intracranial vessels. METHODS: A
      retrospective case review of patients evaluated in an outpatient neuro
      ophthalmology clinic. RESULTS: 10 patients with this condition were identified.
      Dolichoectatic compression was confirmed by magnetic resonance scanning in all
      patients. The average age at presentation was 70.6 years and eight of the 10 were
      female. The carotid artery was involved in seven patients and the basilar in
      three. Patterns of visual loss varied depending on the site of compression. The
      most common pattern in patients with optic neuropathy was nasal field loss. In
      most patients visual loss showed little progression over time. Over an average
      follow up interval of 2.8 years, progressive visual loss was documented in only
      three cases. In one of these, neurosurgical intervention was undertaken with
      subsequent improvement of vision. CONCLUSIONS: Visual loss resulting from
      compression of the visual pathways by dolichoectatic arteries is usually mild and
      only slowly progressive. Most patients are elderly, with other forms of vascular
      disease. Conservative management is thus usually appropriate in this disorder. In
      occasional cases with more rapid progression, surgical intervention may be
      beneficial.

PMID- 14707303
TI  - Oxygen extraction fraction and acetazolamide reactivity in symptomatic carotid
      artery disease.
AB  - OBJECTIVE: It has been proposed that cerebral blood flow (CBF) response to
      acetazolamide may be reduced according to the degree of autoregulatory
      vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the
      CBF response may be absent in regions with increased OEF where vasodilation may
      be maximal in response to reduced perfusion pressure. The objective of this study
      was to test this hypothesis. METHODS: Positron emission tomography (PET) was used
      to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF
      at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide
      was measured. The correlation between the change in CBF during acetazolamide
      administration and the baseline value of OEF in the affected hemisphere was
      examined. RESULTS: The baseline OEF value was inversely and non-linearly
      correlated with the percentage change in CBF during acetazolamide administration
      (R(2) = 0.25, p = 0.02). There was an upward trend of OEF with diminishing
      acetazolamide response below a critical level around zero response. Acetazolamide
      response less than 6.65% over baseline (sensitivity 100%, specificity 89%,
      positive predictive value 50%, negative predictive value 100%) was established as
      most helpful in predicting abnormally high OEF. CONCLUSIONS: The inverse, non
      linear relationship between OEF and CBF response to acetazolamide suggests that
      these two measurements may not identify haemodynamic impairment in the same
      patients.

PMID- 14707304
TI  - Bedside assessment of cerebral perfusion reductions in patients with acute
      ischaemic stroke by near-infrared spectroscopy and indocyanine green.
AB  - OBJECTIVE: To detect perfusion reductions in patients with acute cerebral
      infarcts using near-infrared spectroscopy (NIRS) with indocyanine green (ICG) as
      tracer. METHODS: Kinetics of an intravenous bolus of ICG were monitored by NIRS
      in 13 patients with acute infarction in the territory of the middle cerebral
      artery (mean (SD) age, 62.2 (13.0) years) and 12 controls (64.2 (9.1) years) at
      2.8 (2.8) days after onset. NIRS optodes were placed bitemporally, with an
      interoptode distance of 4-5 cm. Absolute concentration changes in ICG were
      calculated. The following were assessed: time to peak, maximum ICG concentration,
      time interval between 0% and 100% maximum ICG concentration (interval), rise time
      (time between 10% and 90% ICG maximum), slope (maximum Delta ICG/interval), and
      blood flow index (BFI = maximum Delta ICG/rise time) of each hemisphere.
      Intraindividual differences were calculated between the two hemispheres. RESULTS:
      Patients with ischaemic stroke had increased time to peak (p<0.01), interval
      (p<0.01), and rise time (p<0.01), while maximum ICG concentration (p<0.03), slope
      (p<0.01), and BFI (p<0.01) were diminished at the site of infarction compared
      with the unaffected hemisphere. In stroke patients, intraindividual differences
      in time to peak (p<0.001), interval (p<0.001), rise time (p = 0.001), maximum ICG
      concentration (p<0.02), slope (p<0.001), and BFI (p<0.001) were greater than in
      the controls, with excellent sensitivity and specificity for Delta time to peak
      (100% and 100%, respectively) and Delta time interval (100% and 91.7%).
      CONCLUSIONS: Measurement of interhemispheric differences in ICG kinetics by NIRS
      detects perfusion reductions in patients with acute middle cerebral artery
      infarction. This non-invasive bedside test is rapid, repeatable, without major
      side effects, and avoids transportation of critically ill patients.

PMID- 14707306
TI  - The impact of cognitive impairment on upper body dressing difficulties after
      stroke: a video analysis of patterns of recovery.
AB  - OBJECTIVE: to study the underlying cognitive deficits influencing a stroke
      patient's ability to relearn to dress. The aim was to investigate how recovery
      had occurred and whether the nature of cognitive impairment was the reason for
      persistent dressing problems. METHODS: the dressing performance of 30 stroke
      patients was compared at the sub-acute stage and three months later. Standardised
      cognitive and physical tests were carried out, together with a video analysis of
      patients putting on a polo shirt. RESULTS: thirteen patients with preserved power
      in the upper limb used both arms to put on the shirt. Despite visuospatial
      impairment or apraxia in some cases, all were successful given sufficient time.
      Out of 17 patients with arm paresis, 12 were dependent putting on the shirt.
      Amongst the five who were independent, significantly fewer cases of cognitive
      impairment were seen on tests for apraxia (p<0.05) and visuospatial perception
      (p<0.05). Video analysis confirmed the importance of cognitive problems such as
      neglect or apraxia. Three patients who failed shirt dressing showed neglect or
      apraxia at follow up and had persistent arm paresis. Test failures also occurred
      amongst those who were independent. DISCUSSION: cognitive impairment affected
      patients attempting to relearn to dress with one hand, but did not affect
      patients who used both hands. The three patients who remained impaired on
      cognitive tests at follow up were unable to adapt or learn any compensatory
      strategies. The influence of cognition on a person's ability to learn
      compensatory strategies has implications for the design of rehabilitation
      therapies.

PMID- 14707307
TI  - The influence of limb crossing on left tactile extinction.
AB  - BACKGROUND: Previous research on patients with left tactile extinction has shown
      that crossing of hands, so that each hand is on the opposite side of the body
      midline relative to the other, improves detection of stimuli given to the left
      hand. OBJECTIVES: To study the influence of the spatial position of limbs on left
      tactile extinction, and its relations with left visual neglect. METHODS: Normal
      participants and patients with right cerebral hemisphere damage and left tactile
      extinction were asked to detect single or double light touch stimuli applied to
      their cheeks, hands, or knees with their arm and legs either in anatomical or in
      crossed position, increasing the attentional load of the task. RESULTS: In
      patients with left extinction, limb crossing caused a deterioration in
      performance for stimuli applied to right body parts, with only a tendency to an
      improvement in detection for left body parts (only two of 24 patients showed
      substantial (>20%) improvement in left extinction after limb crossing). After
      crossing, left limb detections of double stimuli decreased with increasing
      degrees of visual neglect. CONCLUSIONS: In conditions of high attentional load,
      limb crossing may impair tactile detection in most patients with left extinction,
      and particularly in those showing signs of left visual neglect. These results
      underline the importance of general attentional capacity in determining tactile
      extinction. Attentional and somatotopic mechanisms of extinction may assume
      different weights in different patients.

PMID- 14707308
TI  - The epidemiology of multiple sclerosis in Devon: a comparison of the new and old
      classification criteria.
AB  - OBJECTIVES: To determine the prevalence of multiple sclerosis in Devon and
      compare the new McDonald classification guidelines with the Poser criteria
      currently used. METHODS: All patients known to have multiple sclerosis and alive
      and resident within the chosen area on 1 June 2001 were included in the study.
      Seven sources of case ascertainment were used and each patient was classified
      according to both the Poser criteria and the McDonald guidelines. RESULTS: The
      prevalence of multiple sclerosis in Devon was 118 per 100,000 (definite and
      probable cases, Poser criteria) in a population of 341,796, on the prevalence
      day. The prevalence of definite and possible cases, as classified by the new
      McDonald guidelines, was slightly lower at 117 per 100,000. Clinical demographics
      of the prevalent population were similar to those of other studies in the United
      Kingdom. CONCLUSIONS: This is first survey to use the new recommended guidelines
      and compare these criteria with the Poser classification. The difficulties
      encountered with applying the new criteria in research are highlighted, as are
      the differences between the new and old criteria. This study reports one of the
      highest prevalences in the south of the UK, adding support for a north-south
      divide being a step effect rather than a latitudinal gradient.

PMID- 14707310
TI  - Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular
      dementia.
AB  - BACKGROUND: There are inconsistencies in published reports regarding the profile
      of cognitive impairments in vascular dementia, and its differentiation from
      Alzheimer's disease. OBJECTIVES: To identify the overall profile of cognitive
      impairment in subcortical vascular dementia as compared with Alzheimer's disease;
      and the tests which best discriminate between these groups. METHODS: 57 subjects
      participated: 19 with subcortical vascular dementia, 19 with Alzheimer's disease,
      and 19 controls. The dementia groups were matched for age, education, and general
      levels of cognitive and everyday functioning. Subcortical vascular dementia was
      defined by clinical features (prominent vascular risk factors plus a previous
      history of transient ischaemic events or focal neurological signs) and
      substantial white matter pathology on magnetic resonance imaging. All subjects
      were given a battery of 33 tests assessing episodic and semantic memory,
      executive/attentional functioning, and visuospatial and perceptual skills.
      RESULTS: Despite a minimal degree of overall dementia, both patient groups had
      impairments in all cognitive domains. The Alzheimer patients were more impaired
      than those with vascular dementia on episodic memory, while the patients with
      vascular dementia were more impaired on semantic memory, executive/attentional
      functioning, and visuospatial and perceptual skills. Logistic regression analyses
      showed that the two groups could be discriminated with 89% accuracy on the basis
      of two tests, the WAIS logical memory--delayed recall test and a silhouette
      naming test. CONCLUSIONS: Subcortical vascular dementia and Alzheimer's disease
      produce distinctive profiles of cognitive impairment which can act as an adjunct
      to diagnosis. Many of the neuropsychological deficits thought to characterise
      Alzheimer's disease are also found in subcortical vascular dementia.

PMID- 14707311
TI  - A comparison of adult onset and "classical" idiopathic generalised epilepsy.
AB  - OBJECTIVES: To report the characteristics of a population of patients with
      idiopathic generalised epilepsy (IGE) with age of onset over 20 years, and
      compare them with patients with "classical" IGE. METHODS: Data were collected
      from a computerised database of all patients with IGE attending a regional adult
      epilepsy clinic. Demographic data, epilepsy characteristics, and treatment
      outcomes were recorded. RESULTS: 72 patients with IGE of a total population of
      844 had an age of onset over 20 years (8.5%). There was similar incidence of
      family history of epilepsy, EEG findings, and remission rates between those with
      a younger and older age of onset of IGE. There was a lower incidence of previous
      febrile convulsions in patients with adult onset. There were fewer patients with
      absence seizures in the adult onset group (15.3% v 46.4% in the "classical"
      group). CONCLUSIONS: IGE with onset later than the third decade was rare in the
      population studied. Prolonged EEG in selected patients may be helpful in
      diagnosing adult onset IGE, but the diagnosis of epilepsy remains clinical. Adult
      onset IGE shares many features with "classical" IGE, including EEG findings and
      prognosis, and is likely to represent a genetic epilepsy.

PMID- 14707312
TI  - The relationship between treatment with valproate, lamotrigine, and topiramate
      and the prognosis of the idiopathic generalised epilepsies.
AB  - OBJECTIVE: To examine a large population with idiopathic generalised epilepsy
      (IGE), and estimate the overall remission rates for the IGEs and subsyndromes in
      a clinic based sample. Remission rates on valproate, lamotrigine, topiramate, and
      combinations of these antiepileptic drugs were estimated and factors predicting
      outcome examined. METHODS: All patients with IGE were identified from a
      computerised database and EEG records at large adult and paediatric epilepsy
      clinics. Data were recorded retrospectively on demographics and clinical
      information, seizure types and syndrome diagnosis, antiepileptic drug treatment
      details, and remission rates. RESULTS: 54.3% of 962 patients had achieved a one
      year period of remission; this was most likely with valproate monotherapy
      (52.1%), with lower rates for lamotrigine and topiramate (16.7% and 34.6%,
      respectively). The combination of valproate and lamotrigine achieved a remission
      rate of 15.3%. The factor most predictive of a response to a particular
      antiepileptic drug regimen was the rank order in which it was given. Relapse rate
      was high (79.9%) after antiepileptic drug withdrawal in remission, particularly
      with juvenile myoclonic epilepsy (93.6%). CONCLUSIONS: Valproate may be the most
      effective antiepileptic drug in the treatment of the IGEs. Combination therapy
      should be initiated if an adequate trial of valproate monotherapy is not
      effective, rather than switching to alternative monotherapy. Antiepileptic drug
      treatment needs to be lifelong in many adult patients with IGE.

PMID- 14707313
TI  - Visual command hallucinations in a patient with pure alexia.
AB  - Around 25% of patients with visual hallucinations secondary to eye disease report
      hallucinations of text. The hallucinated text conveys little if any meaning,
      typically consisting of individual letters, words, or nonsense letter strings
      (orthographic hallucinations). A patient is described with textual visual
      hallucinations of a very different linguistic content following bilateral
      occipito-temporal infarcts. The hallucinations consisted of grammatically
      correct, meaningful written sentences or phrases, often in the second person and
      with a threatening and command-like nature (syntacto-semantic visual
      hallucinations). A detailed phenomenological interview and visual psychophysical
      testing were undertaken. The patient showed a classical ventral occipito-temporal
      syndrome with achromatopsia, prosopagnosia, and associative visual agnosia. Of
      particular significance was the presence of pure alexia. Illusions of colour
      induced by monochromatic gratings and a novel motion-direction illusion were also
      observed, both consistent with the residual capacities of the patient's spared
      visual cortex. The content of orthographic visual hallucinations matches the
      known specialisations of an area in the left posterior fusiform gyrus--the visual
      word form area (VWFA)--suggesting the two are related. The VWFA is unlikely to be
      responsible for the syntacto-semantic hallucinations described here as the
      patient had a pure alexic syndrome, a known consequence of VWFA lesions. Syntacto
      semantic visual hallucinations may represent a separate category of textual
      hallucinations related to the cortical network implicated in the auditory
      hallucinations of schizophrenia.

PMID- 14707314
TI  - Zero tolerance to shunt infections: can it be achieved?
AB  - OBJECTIVE: To evaluate the rigid application of a technique of shunt placement
      aimed at the eradication of postoperative shunt infection in neurosurgical
      practice. METHOD: All shunt procedures were performed or closely supervised by
      the senior author (MSC). The essentials were the use of intravenous peri- and
      postoperative antimicrobials, rigid adherence to classical aseptic technique,
      liberal use of topical antiseptic (Betadine), and avoidance of haematomas.
      RESULTS: Of 176 operations, 93 were primary procedures; 33 patients underwent
      revisions, some multiple. Only one infection occurred, seven months
      postoperatively, secondary to appendicitis with peritonitis. The infecting
      Streptococcus faecalis appeared to ascend from the abdominal cavity. CONCLUSION:
      A rigidly applied protocol and strict adherence to sterile technique can reduce
      shunt infections to a very low level.

PMID- 14707315
TI  - Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS
      1 study, a 12 week, randomised, placebo controlled study in 10 European
      countries.
AB  - OBJECTIVE: To assess the efficacy, safety, and tolerability of ropinirole in the
      treatment of patients with restless legs syndrome. METHODS: A 12 week,
      prospective, double blind, randomised comparison involving 284 patients from 10
      European countries. All participants had a score of > or =15 on the international
      restless legs scale (IRLS). Patients were randomised (1:1) to receive either
      ropinirole 0.25-4.0 mg once daily or placebo. The primary efficacy end point was
      mean change from baseline to week 12 in total IRLS score. Global improvements
      (clinical global impression (CGI) scale) and improvements in sleep, health
      related quality of life (QoL; using generic and disease specific measures), work,
      and other activities were also assessed. RESULTS: 112/146 patients (76.7%) taking
      ropinirole and 109/138 (79.0%) taking placebo completed the study. Improvement in
      IRLS at week 12 with ropinirole (mean (SD) dose, 1.90 (1.13) mg/day) was greater
      than with placebo (mean (SE): -11.04 (0.719) v -8.03 (0.738) points; adjusted
      difference = -3.01 (95% confidence interval (CI), -5.03 to -0.99); p = 0.0036).
      More patients in the ropinirole group (53.4%) showed improvement on the CGI scale
      at week 12 than in the placebo group (40.9%; adjusted odds ratio = 1.7 (1.02 to
      2.69); p = 0.0416). Significant differences on both IRLS and CGI scales favouring
      ropinirole were apparent by week 1. Ropinirole was also associated with
      significantly greater improvements in sleep and QoL end points. The most common
      adverse events were nausea and headache. CONCLUSIONS: Ropinirole improves
      restless legs syndrome compared with placebo, with benefits apparent by week 1.
      It is generally well tolerated.

PMID- 14707316
TI  - Persistence of pain induced by startle and forehead cooling after sympathetic
      blockade in patients with complex regional pain syndrome.
AB  - BACKGROUND: Stimuli arousing sympathetic activity can increase ratings of
      clinical pain in patients with complex regional pain syndrome (CRPS). OBJECTIVE:
      To determine whether the increase in pain is mediated by peripheral sympathetic
      activity. METHODS: The effect of sympathetic ganglion blockade on pain evoked by
      a startle stimulus and cooling the forehead was investigated in 36 CRPS patients.
      RESULTS: Loss of vasoconstrictor reflexes and warming of the limb indicated that
      sympathetic blockade was effective in 26 cases. Before sympathetic blockade, pain
      increased in 12 of these 26 patients when they were startled. Pain increased in
      seven of the 12 patients and in another five cases when their forehead was
      cooled. As expected, pain that increased during sympathetic arousal generally
      subsided in patients with signs of sympathetic blockade. However, pain still
      increased in three of 12 of patients after the startle stimulus and in six of 12
      of patients during forehead cooling, despite indisputable sympathetic blockade.
      CONCLUSIONS: These findings suggest that stimuli arousing sympathetic activity
      act by a central process to exacerbate pain in some patients, independent of the
      peripheral sympathetic nervous system. This may account for the lack of effect of
      peripheral sympathetic blockade on pain in some CRPS patients.

PMID- 14707317
TI  - Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction
      in pontine base as a valuable diagnostic marker.
AB  - OBJECTIVE: We performed (1)H-MR spectroscopy ((1)H-MRS) on multiple brain regions
      to determine the metabolite pattern and diagnostic utility of (1)H-MRS in
      multiple system atrophy (MSA). METHODS: Examining single voxels at 3.0 T, we
      studied metabolic findings of the putamen, pontine base, and cerebral white
      matter in 24 MSA patients (predominant cerebellar ataxia (MSA-C), n = 13),
      parkinsonism (MSA-P), n = 11), in 11 age and duration matched Parkinson's disease
      patients (PD) and in 18 age matched control subjects. RESULTS: The N
      acetylaspartate to creatine ratio (NAA/Cr) in MSA patients showed a significant
      reduction in the pontine base (p<0.0001) and putamen (p = 0.02) compared with
      controls. NAA/Cr in cerebral white matter also tended to decline in long standing
      cases. NAA/Cr reduction in the pontine base was prominent in both MSA-P
      (p<0.0001) and MSA-C (p<0.0001), and putaminal NAA/Cr reduction was significant
      in MSA-P (p = 0.009). It was also significant in patients who were in an early
      phase of their disease, and in those who showed no ataxic symptoms or
      parkinsonism, or did not show any MRI abnormality of the "hot cross bun" sign or
      hyperintense putaminal rims. NAA/Cr in MSA-P patients was significantly reduced
      in the pontine base (p = 0.001) and putamen (p = 0.002) compared with PD
      patients. The combined (1)H-MRS in the putamen and pontine base served to
      distinguish patients with MSA-P from PD more clearly. CONCLUSIONS: (1)H-MRS
      showed widespread neuronal and axonal involvement in MSA. The NAA/Cr reduction in
      the pontine base proved highly informative in the early diagnosis of MSA prior to
      MRI changes and even before any clinical manifestation of symptoms.

PMID- 14707318
TI  - Abnormal baroreceptor-mediated vasopressin release as possible marker in early
      diagnosis of multiple system atrophy.
AB  - BACKGROUND: Although autonomic failure (AF) is a critical symptom of multiple
      system atrophy (MSA), it may not appear until late in the disease process.
      OBJECTIVES: To clarify whether a detailed investigation of the autonomic nervous
      system in patients with MSA without overt AF demonstrates latent lesions of
      central cardiovascular control circuits and facilitates the early diagnosis of
      MSA. METHODS: Autonomic function tests, and plasma noradrenaline (NA) and
      vasopressin (AVP) responses to head-up tilt (HUT), were studied in 12 patients
      with MSA with AF (probable MSA), 12 with MSA without overt AF (possible MSA), and
      24 controls. RESULTS: Abnormalities of cardiovascular autonomic function tests
      were prominent in the first group but mild in the second. Plasma NA and AVP
      increments upon HUT differed significantly among all three groups. CONCLUSIONS:
      These results indicate that probable MSA involves diffuse degeneration of central
      cardiovascular control circuits. On the other hand, the discrepancies in possible
      MSA suggest a vulnerability of the noradrenergic (A1) neurones of the caudal
      ventrolateral medulla that are involved in AVP secretion. This finding also
      suggests that AVP increment may be useful as a diagnostic tool in the early
      stages of MSA.

PMID- 14707319
TI  - Hippocampal MRI volumetry in cognitively discordant monozygotic twin pairs.
AB  - OBJECTIVE: To investigate whether hippocampal atrophy, a proxy for incipient
      Alzheimer's disease, can be detected in non-demented monozygotic co-twins of
      demented twins by using volumetric magnetic resonance imaging (MRI). METHODS:
      Seven pairs of monozygotic female twins discordant for cognitive function (mean
      (SD) age 75 (4) years), and 10 age and education matched healthy controls (seven
      women, three men; mean age 73 (3) years) were studied with volumetric MRI.
      RESULTS: The mean normalised right hippocampal volume was 31% lower (p = 0.002)
      in the demented twins, and 6% lower (p = 0.45) in the non-demented twins than in
      the controls. In the left hippocampus, the mean normalised volume was 36% lower
      (p<0.001) in the demented twins, and 9% lower (p = 0.13) in the non-demented
      twins than in the controls. CONCLUSIONS: Significant hippocampal atrophy was
      detected in the demented twins compared with the controls. This is in line with
      previous imaging and pathological studies, with hippocampus showing the early
      changes in Alzheimer's disease. In the non-demented twins, only a minor, non
      significant reduction was observed in the hippocampal volumes compared with the
      controls. This could reflect gene-environment interactions that have protected
      the non-demented twins longer than their demented co-twins and contributed to the
      relative preservation of their hippocampal volumes, or it could be a sign of
      preclinical Alzheimer's disease in the non-demented twins.

PMID- 14707320
TI  - Abductor sign: a reliable new sign to detect unilateral non-organic paresis of
      the lower limb.
AB  - OBJECTIVES: To test a new neurological sign, the "abductor sign," which can
      distinguish between organic and non-organic leg paresis using synergic movements
      of the bilateral hip abductors. METHODS: The subjects were 33 patients presenting
      with paresis of one leg, 17 of organic origin and 16 of non-organic origin
      (hysteria). To test the abductor sign, the examiner told the patient to abduct
      each leg, and opposed this movement with his hands placed on the lateral surfaces
      of the patient's legs. The leg contralateral to the abducted one showed opposite
      actions for organic paresis and non-organic paresis: for example, when the
      paretic leg was abducted, the sound leg stayed fixed in organic paresis, but
      moved in the hyperadducting direction in non-organic paresis. Hoover's sign was
      used for comparison in the same patients. RESULTS: The abductor sign gave the
      correct classification for all 33 cases. Hoover's sign was reliable if the
      results were carefully interpreted, but it was non-diagnostic for 16 patients
      because of strong hip extensors and in two because of strong hip flexors. Two
      patients with non-organic paresis succeeded in tricking the examiner by
      pretending full effort to lift the paretic leg. CONCLUSIONS: The abductor sign is
      a useful test to detect non-organic paresis, because (1) it is difficult for a
      hysterical patient to deceive the examiner, (2) the hip abductor is one of the
      most commonly involved muscles in pyramidal weakness, and (3) the results are
      easily visible as movement or non-movement of the unabducted leg.

PMID- 14707321
TI  - Depressive symptoms and cognitive decline in a community population of older
      persons.
AB  - BACKGROUND: An association between depressive symptoms and cognitive decline has
      been observed in selected cohorts of older people, but studies of defined
      populations have had conflicting results. OBJECTIVE: To test whether the level of
      depressive symptoms predicted the rate of cognitive decline in a biracial
      community of older persons. METHODS: 4392 older people (88% of those eligible)
      from a defined community in Chicago completed two or three structured interviews
      at approximately three year intervals for an average of 5.3 years. At the
      baseline interview, the number of depressive symptoms was assessed with a 10 item
      version of the Center for Epidemiologic Studies Depression scale. Cognitive
      function was assessed at each interview with four performance tests, from which a
      previously established measure of global cognition was derived. Random effects
      models were used to assess change in cognition and its relation to depressive
      symptoms, controlling for age, sex, race, education, and baseline cognitive
      function. RESULTS: Participants reported a median of one depressive symptom at
      baseline (interquartile range, 0 to 2). For each depressive symptom, the rate of
      cognitive decline increased by a mean of about 5%. Results were not substantially
      changed when persons with cognitive impairment at baseline were excluded, or when
      chronic illness or participation in cognitively stimulating activities was
      controlled, and the association was not modified by age, sex, race, or education.
      CONCLUSIONS: The results suggest that depressive symptoms predict cognitive
      decline in old age.

PMID- 14707322
TI  - Modulation of the transmission in group II heteronymous pathways by tizanidine in
      spastic hemiplegic patients.
AB  - OBJECTIVE: To investigate the effect of tizanidine (an alpha(2) noradrenergic
      agonist) on transmission in the interneuronal pathway coactivated by group I and
      group II afferents in post-stroke patients with spastic hemiplegia. METHODS:
      Early and late facilitation of the quadriceps H reflex elicited in the common
      peroneal nerve--attributed to non-monosynaptic group I and group II excitation,
      respectively--was investigated in 14 spastic hemiplegic patients. All received a
      single dose of tizanidine (150 microg/kg) or placebo in randomised order at 10
      day intervals. Repeated measurements were made at baseline (T0), 45-90 min, and
      120 min after drug intake. Spasticity was assessed by modified Ashworth score in
      the quadriceps muscle and by a leg tone score calculated by the sum of the
      modified Ashworth score in five muscle groups. RESULTS: On the spastic side a
      decrease in late group II and, to a lesser extent, early group I common peroneal
      nerve induced quadriceps H reflex facilitation occurred with tizanidine (group
      II, mean (SEM) difference T0-T90: 34.3 (10.2)%, p<0.001; group I, T0-T120: 19.8
      (9)%, p<0.05), but not with placebo (group II, difference T0-T90: 12.5 (8)%, NS;
      group I, T0-T120: 3.2 (7)%, NS). Tizanidine but not placebo decreased the
      quadriceps muscle and global lower limb Ashworth scores (2.9 (0.2) to 1.9 (0.3),
      p<0.001; and 12 (0.7) to 9.5 (0.8), p<0.0001, respectively). CONCLUSIONS:
      Enhancement of group II-group I facilitation of the quadriceps motor neurones on
      the spastic side of hemiplegic patients is modulated by alpha(2) noradrenergic
      agonists. This strengthens the view that late facilitation of quadriceps motor
      neurones is mediated by group II afferents and suggests that group II pathways
      may be involved in lower limb spasticity.

PMID- 14707323
TI  - Diagnostic value of MHC class I staining in idiopathic inflammatory myopathies.
AB  - BACKGROUND: Identification of mononuclear cellular infiltrates in skeletal muscle
      tissue is the histological cornerstone of the diagnosis of idiopathic
      inflammatory myopathy (IIM). However, these infiltrates are not always present.
      OBJECTIVE: To determine whether MHC class I antigen expression on the sarcolemma,
      which is absent in normal muscle tissue, is upregulated in IIM and could serve as
      an additional diagnostic test. METHODS: Expression of MHC class I antigens was
      studied in 224 muscle samples of 61 adult patients with IIM (9 dermatomyositis,
      23 polymyositis, 29 inclusion body myositis) and 163 controls (normal subjects
      and patients with various neuromuscular disorders) in a prospective blinded
      manner. RESULTS: The sensitivity of the test for diagnosing IIM was 78% (95%
      confidence interval (CI), 66% to 88%), with a specificity of 95% (91% to 98%).
      The sensitivity before the start of immunosuppressive treatment was 89% (76% to
      96%). The sensitivity was not changed by including all patients who had been on
      immunosuppressive treatment for less than four weeks before muscle biopsy
      (sensitivity 90% (79% to 97%)). False positive results were found in only seven
      controls (4%), six of whom had a muscular dystrophy. CONCLUSIONS: Detection of
      sarcolemmal MHC class I is a valid test for IIM. It is not affected by the short
      term use of immunosuppressive agents (less than four weeks) and it should be
      incorporated in the histological evaluation when the diagnosis of IIM is under
      consideration or needs to be excluded.

PMID- 14707324
TI  - Double pituitary adenomas with distinct histological features and
      immunophenotypes.

PMID- 14707325
TI  - Duration of amantadine benefit on dyskinesia of severe Parkinson's disease.
AB  - BACKGROUND: Recent short-term studies suggested that amantadine (Ama) might
      ameliorate dyskinesia in patients with Parkinson's disease. A double-blind study
      programmed over 12 months was designed to assess the duration of the
      antidyskinetic effect of amantadine on levodopa induced dyskinesia. METHODS: 40
      patients treated for 7.5 (2.2) years with levodopa (729.3 (199.4) mg/day) and
      dopaminoagonists, having peak dose or dyphasic dyskinesia with or without pain,
      were assessed with the Unified Parkinson's Disease Rating Scale subscale IV,
      Items 32-34, the Dyskinesia Rating Scale and Investigator Global Assessment.
      Twenty patients received amantadine chloridrate (100 mg) and 20 received a
      placebo. The Ama or placebo could be withdrawn when scores indicated worsening of
      dyskinesia, after agreement with the patient. RESULTS: After 15 days of
      amantadine treatment there was a reduction by 45% in the total dyskinesia scores.
      All patients in the placebo group were withdrawn in 1-3 months and all patients
      in the Ama group were withdrawn in 3-8 months (p = 0.01, p<0.001). Ama withdrawal
      induced a rebound with increase of dyskinesia by 10-20% in 11 patients.
      CONCLUSION: 300 mg amantadine reduces dyskinesia in Parkinson's disease by
      approximately 45% but the benefit lasted less than eight months.

PMID- 14707326
TI  - DJ-1 mutations in Parkinson's disease.
AB  - Mutations in the DJ-1 gene have recently been shown to cause autosomal recessive
      Parkinson's disease. To estimate the prevalence of this mutation, an analysis was
      undertaken of 39 index cases of Parkinson's disease in whom a family history
      suggested autosomal recessive inheritance. No DJ-1 mutations were found in these
      patients, indicating that this gene is unlikely to be of numerical significance
      in clinical practice. The hypothesis was also tested that young onset Parkinson's
      disease patients in whom, despite extensive analysis, only a single heterozygous
      parkin mutation was found, might harbour a second mutation in the DJ-1 gene--that
      is, digenic inheritance. No patient was found with a single mutation in both DJ-1
      and parkin genes, making this mode of inheritance unlikely. Finally it was
      confirmed that PARK6 and PARK7 (DJ-1), despite being phenotypically similar and
      mapping to the same small chromosomal region of 1p36, are caused by mutations in
      separate genes.

PMID- 14707327
TI  - Dementia associated mental and behavioural disturbances in elderly people in the
      community: findings from the first Nakayama study.
AB  - OBJECTIVE: To determine the prevalence of mental and behavioural disturbances
      associated with dementia in elderly people living in the Japanese community of
      Nakayama. METHODS: A door to door three phase population survey was carried out
      on all persons aged 65 years and older living at home. The study included a
      psychiatric interview, neurological and neuropsychological examination, and
      cranial computed tomography. Participants with dementia were rated on the
      neuropsychiatric inventory. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed
      the protocol. The prevalence of dementia was 4.8%. Of the 60 participants with
      dementia (Alzheimer's disease 35%, vascular dementia 47%, and dementia from other
      causes 17%), 53 (88.3%) had shown one or more mental and behavioural
      disturbances. Apathy/indifference (56.7%), followed by agitation/aggression
      (35%), aberrant motor behaviour (31.7%), and irritability (31.7%) were the common
      symptoms. More productive (positive) symptoms such as delusions and aberrant
      motor behaviour were found in the Alzheimer group than in the vascular dementia
      group. CONCLUSIONS: A wide range of dementia associated mental and behavioural
      disturbances developed in the majority of community dwelling individuals with
      dementia. The findings suggest that a screening programme focusing on identifying
      these symptoms should be included in the physician's diagnostic tools for
      dementia.

PMID- 14707328
TI  - Aphasia after hemispherectomy in an adult with early onset epilepsy and
      hemiplegia.
AB  - A 55 year old left handed man with left hemisphere subcortical encephalomalacia,
      seizures, language impairment, and right hemiparesis from a motor vehicle
      accident at age five was evaluated for epilepsy surgery. The patient continued to
      speak and followed commands during a left intracarotid amobarbital test (IAT).
      Left functional hemispherectomy resulted in expressive aphasia. Based on
      postoperative outcome, language was bilateral. The injury after primary
      development of language function, the predominantly subcortical lesion, and the
      late timing of surgical intervention well past development and plasticity may
      have been factors in the emergence of postoperative aphasia.

PMID- 14707329
TI  - Chlamydophila pneumoniae infection of the central nervous system in patients with
      multiple sclerosis.
AB  - BACKGROUND: Chlamydophila pneumoniae has been postulated as an aetiological agent
      in the pathophysiology of multiple sclerosis. Previous studies show conflicting
      results. OBJECTIVE: To investigate patients with multiple sclerosis and other
      neurological diseases for evidence of past or present infection with C
      pneumoniae. METHODS: 19 patients with multiple sclerosis and 29 with other
      neurological diseases were studied. Evidence was sought for past or present
      infection with C pneumoniae using polymerase chain reaction (PCR) and cell
      culture of cerebrospinal fluid (CSF), and enzyme linked immunosorbent assay and
      microimmunofluorescence of serum. RESULTS: C pneumoniae was grown from the CSF of
      one patient with multiple sclerosis. PCR was negative in all cases. Anti
      chlamydial antibodies were detected in the same proportion in each group.
      CONCLUSIONS: This study does not support the theory of an association between C
      pneumoniae and multiple sclerosis.

PMID- 14707330
TI  - Sequence analysis of tau 3'untranslated region and saitohin gene in sporadic
      progressive supranuclear palsy.
AB  - BACKGROUND: The extended tau H1 haplotype has previously been described in
      association with progressive supranuclear palsy (PSP). Recently, a new gene
      called saitohin (STH), nested within an intron of tau, has been discovered. The
      Q7R polymorphism of STH appears to be related to late onset Alzheimer's disease.
      OBJECTIVES: To search for genetic changes in the 3'untranslated region (3'UTR) of
      tau and adjacent sequence LOC147077, and in the coding region of STH in PSP
      patients. METHODS: The study included 57 PSP patients and 83 healthy controls.
      The genetic analysis of each region was performed through sequencing. The Q7R
      polymorphism was studied through restriction enzyme and electrophoresis analysis.
      RESULTS: No mutations were found in the regions analysed. The QQ genotype of the
      STH polymorphism was over-represented in participants with PSP (91.5%) compared
      with control subjects (47%) (p< or =0.00001). This genotype co-segregated with
      the H1/H1 haplotype in our PSP cases. CONCLUSIONS: Our results do not support a
      major role for the tau 3'UTR in PSP genetics. The QQ genotype of STH confers
      susceptibility for PSP and is in linkage disequilibrium with the H1/H1 haplotype.

PMID- 14707331
TI  - The breathing hand: obstetric brachial plexopathy reinnervation from thoracic
      roots?
AB  - It has been found that in cases of obstetric brachial plexopathy, injured phrenic
      nerve or C3/4/5 roots may sprout into the adjacent injured upper and middle
      trunks of the brachial plexus. This aberrant regeneration produces co-contraction
      of the diaphragm and proximal upper limb muscles. This phenomenon, referred to as
      respiratory synkinesis or "the breathing arm", may not be limited to the upper
      cervical roots. We present two cases, identified through electromyographic
      investigations, of respiratory synkinesis selectively affecting intrinsic hand
      muscles, and propose that upper thoracic roots and their intercostal nerves may
      also produce respiratory synkinesis, resulting in a "breathing hand." This novel
      brand of synkinesis indicates that obstetric brachial plexus neuropathies can
      have quite proximal nerve injury in all trunks. The findings in our patients may
      not be entirely unique. The time required to develop distal muscle synkinesis and
      the subtle nature of our findings may suggest that with time and the assistance
      of EMG the breathing hand may be more common. When considering brachial plexus
      surgery, the significance of respiratory synkinesis should not be overlooked as
      its presence indicates injury at a root or proximal trunk level and may come from
      either nerves destined for the diaphragm or for the intercostal muscles.

PMID- 14707332
TI  - Predictive value of Glasgow Coma Scale after brain trauma: change in trend over
      the past ten years.
AB  - BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are
      considered important predictors of outcome after traumatic brain injury. We
      investigated the predictive value of the GCS in a large group of patients whose
      computerised multimodal bedside monitoring data had been collected over the
      previous 10 years. METHODS: Data from 358 subjects with head injury, collected
      between 1992 and 2001, were analysed retrospectively. Patients were grouped
      according to year of admission. Glasgow Outcome Scores (GOS) were determined at
      six months. Spearman's correlation coefficients between GCS and GOS scores were
      calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored
      every year. We found a significant correlation between the GCS and GOS for the
      first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent
      lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226;
      n = 175). In contrast, correlations between age and GOS were in both time periods
      significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The
      admission GCS lost its predictive value for outcome in this group of patients
      from 1997 onwards. The predictive value of the GCS should be carefully
      reconsidered when building prognostic models incorporating multimodality
      monitoring after head injury.

PMID- 14707333
TI  - The androgen receptor CAG repeat and serum testosterone in the risk of
      Alzheimer's disease in men.

PMID- 14707334
TI  - Subthalamic nucleus stimulation in a parkinsonian patient with previous bilateral
      thalamotomy.

PMID- 14707335
TI  - Testosterone deficiency in a Parkinson's disease clinic: results of a survey.

PMID- 14707336
TI  - LBP-1c/CP2/LSF gene polymorphism and risk of sporadic Alzheimer's disease.

PMID- 14707337
TI  - Vestibular stimulation in mania: a case report.

PMID- 14707338
TI  - Hand weakness onset Guillain-Barre syndrome.

PMID- 14707339
TI  - Lack of association between interleukin-1 beta polymorphism (-511) and ischaemic
      stroke.

PMID- 14707340
TI  - Intracranial hypertension and giant arachnoid granulations.

PMID- 14707341
TI  - The chromosomes of Drosophila melanogaster.

PMID- 14707342
TI  - Spermatogenesis: analysis of meiosis and morphogenesis.

PMID- 14707343
TI  - Time-lapse imaging of male meiosis by phase-contrast and fluorescence microscopy.

PMID- 14707344
TI  - Immunocytological analysis of oogenesis.

PMID- 14707345
TI  - Cytological analysis of oogenesis.

PMID- 14707346
TI  - Polytene chromosomes from ovarian nurse cells of Drosophila melanogaster otu
      mutants.

PMID- 14707347
TI  - Feulgen-DNA cytophotometry for estimating C values.

PMID- 14707348
TI  - Fluorescent BrdU labeling and nuclear flow sorting of the Drosophila ovary.

PMID- 14707349
TI  - Studying nuclear organization in embryos using antibody tools.

PMID- 14707350
TI  - Whole-mount fluorescence in situ hybridization to chromosomes of embryos.

PMID- 14707351
TI  - Orcein staining and the identification of polytene chromosomes.
AB  - Acetic orcein staining of polytene chromosomes was introduced in 1941 shortly
      after the initial studies on aceto-carmine-stained chromosomes by Bridges (2) and
      has remained a standard method of preparation. Orcein dye can be purchased in
      both its natural form as extracted from two species of lichens, Rocella tinctoria
      and Lecanora parella, and a synthetic form. The mechanism of staining is not
      clearly understood because the stain itself is a variety of phenazones, which may
      interact at an acid pH with negatively charged groups or possibly interact
      hydrophobically with chromatin. Acetic acid fixation accommodates stretching of
      the chromosomes in the interband regions during a squash, thus providing for a
      higher resolution of the banding structure. The later addition of lactic acid to
      aceto-orcein (3) kept the glands softer in the fix and allowed for easier
      spreading of chromosomes. The method and its variations have appeared more
      recently in several publications (4,5). Drosophila polytene chromosomes are found
      in a number of larval tissues, including the midgut, hindgut, and the fat body,
      but the largest chromosomes are found in the salivary glands of the third instar.
      They are referred to as interphase chromosomes and are structurally more
      comparable to highly amplified interphase chromatin than to mitotic chromosomes
      because the gland grows by endoreplication of DNA, thus increasing cell size
      rather than cell number. Each of the homologs is tightly synapsed in this somatic
      tissue and undergoes approx 10 rounds of endoreplication, producing 1024
      chromatids closely associated in parallel arrays.

PMID- 14707352
TI  - Salivary chromosome analysis of aberrations.

PMID- 14707353
TI  - In situ hybridization to polytene chromosomes.

PMID- 14707354
TI  - Combined immunostaining and FISH analysis of polytene chromosomes.

PMID- 14707355
TI  - Electron microscopy of polytene chromosomes.

PMID- 14707356
TI  - Analysis of mitosis in squash preparations of larval brains: orcein, Giemsa,
      Hoechst 33258, DAPI, quinacrine, and N-banding.

PMID- 14707357
TI  - Analyzing chromosome function by high frequency formation of dicentric
      chromosomes in vivo.

PMID- 14707358
TI  - Analysis of chromosomes of the larval CNS by FISH and BrdU labeling.

PMID- 14707359
TI  - Immunostaining of squash preparations of chromosomes of larval brains.

PMID- 14707360
TI  - Visualizing mitosis in whole-mount larval brains.

PMID- 14707361
TI  - Immunostaining of whole-mount imaginal discs.

PMID- 14707362
TI  - Wing somatic mutation and recombination test.

PMID- 14707363
TI  - Analysis of histoblasts.

PMID- 14707364
TI  - Visualizing apoptosis.

PMID- 14707366
TI  - Chemical methods for DNA delivery: an overview.

PMID- 14707367
TI  - Gene transfer into mammalian cells using calcium phosphate and DEAE-dextran.

PMID- 14707365
TI  - RNAi in cultured Drosophila cells.

PMID- 14707368
TI  - DNA delivery to cells in culture using peptides.

PMID- 14707369
TI  - DNA delivery to cells in culture using PNA clamps.

PMID- 14707370
TI  - Dendrimer-mediated cell transfection in vitro.

PMID- 14707371
TI  - DNA delivery to cells in culture using cationic liposomes.

PMID- 14707372
TI  - Formulation of synthetic gene delivery vectors for transduction of the airway
      epithelium.

PMID- 14707373
TI  - Cationic liposome-mediated DNA delivery to the lung endothelium.

PMID- 14707374
TI  - Delivery of DNA to tumor cells using cationic liposomes.

PMID- 14707375
TI  - Delivery of transposon DNA to lungs of mice using polyethyleneimine-DNA
      complexes.

PMID- 14707376
TI  - Gene delivery using physical methods: an overview.

PMID- 14707377
TI  - Gene delivery to mammalian cells by microinjection.

PMID- 14707378
TI  - Delivery of DNA to cells in culture using particle bombardment.

PMID- 14707379
TI  - Delivery of DNA to skin by particle bombardment.

PMID- 14707380
TI  - Biolistic transfection of cultured organotypic brain slices.

PMID- 14707381
TI  - Efficient electroporation of mammalian cells in culture.

PMID- 14707382
TI  - Delivery of DNA to skin by electroporation.

PMID- 14707383
TI  - In vivo DNA electrotransfer in skeletal muscle.

PMID- 14707384
TI  - Electrically mediated plasmid DNA delivery to solid tumors in vivo.

PMID- 14707385
TI  - Hydrodynamic delivery of DNA.

PMID- 14707386
TI  - Naked DNA gene transfer in mammalian cells.

PMID- 14707387
TI  - Microparticle delivery of plasmid DNA to mammalian cells.

PMID- 14707388
TI  - DNA delivery to cells in culture using ultrasound.

PMID- 14707389
TI  - DNA delivery to cells in vivo by ultrasound.

PMID- 14707390
TI  - Trans- and retroperitoneal endoscopic adrenalectomy: experience in 26 consecutive
      adrenalectomies.
AB  - OBJECTIVE: To assess our current concept and results of transperitoneal
      laparoscopic adrenalectomy (TPLA) and retroperitoneal endoscopic adrenalectomy
      (ERA) for a variety of benign disorders of the adrenal glands. BACKGROUND DATA:
      According to the literature, minimal invasive adrenalectomy has shown to be a
      safe and effective surgical alternative to open adrenalectomy. Both,
      transperitoneal and retroperitoneal endoscopic minimal invasive access are
      currently used for surgical removal of benign adrenal tumors. There is still some
      debate about the indications and the access used for a minimal invasive approach.
      PATIENTS AND METHODS: Treatment and clinical outcome of all patients who
      underwent either transperitoneal laparoscopic or endoscopic retroperitoneal
      adrenalectomies for benign diseases from February 1997 to August 2002 were
      analyzed retrospectively. RESULTS: Twenty-six minimal invasive adrenalectomies
      were performed in 23 patients with a mean age of 57 years. Whereas 11 patients
      underwent unilateral right- sided ERA, unilateral TPLA was performed in 9
      patients on the left side. Three patients had bilateral TPLA. The mean operating
      time for unilateral ERA and TPLA was 114 and 79 min, respectively. Bilateral TPLA
      was prolonged to 223 min operating time. There were only two minor postoperative
      complications. The mean hospital stay for unilateral TPLA, ERA and bilateral TPLA
      was 4.7, 5 and 6 days, respectively. There was no mortality. CONCLUSION: Both,
      ERA and TPLA are safe and clinically effective treatment modalities for benign
      disorders of the adrenal glands. We currently favor a transperitoneal
      laparoscopic approach for bilateral and left-sided adrenal tumors, whereas right
      sided tumors <8 cm are removed by a retroperitoneal approach. Large right-sided
      tumors >8 cm are better removed by transperitoneal access.

PMID- 14707391
TI  - Colonic involvement in acute pancreatitis. A retrospective study of 16 patients.
AB  - BACKGROUND: Diagnosis of colonic pathology complicating acute pancreatitis is
      difficult. Several pathogenetic mechanisms have been proposed. The treatment of
      choice is resection of the affected segment. Current theories on diagnosis,
      pathogenesis, and treatment were reviewed. METHOD: Retrospectively, 16 patients
      with severe acute pancreatitis and colonic complications (1988-2001) were
      included. Preoperative CT scans and specimens of removed colonic segments were
      reviewed by a blinded radiologist and pathologist respectively. RESULTS: Sixteen
      patients underwent partial colectomy for suspected imminent or overt perforation,
      based on the outer aspect of the colon. Four patients had a macroscopic
      perforation during surgery. Retroperitoneal spread of the necrotizing process to
      the colon was seen in all 10 reviewed CT scans. All 14 microscopically examined
      specimens showed fat necrosis and pericolitis. Of these, 4 had ischemia and 6
      showed subserosal hemorrhage. Eight specimens had intact mucosa, submucosa and
      smooth muscle layers. Eleven patients died. Secondary anastomosis in surviving
      patients did not induce further mortality. CONCLUSION: Spread of pancreatic
      enzymes and necrosis is the major cause for colonic pathology in acute
      pancreatitis. Outside inspection of the colon during surgery is unreliable to
      detect ischemia or imminent perforation. To prevent colonic complications during
      follow-up, low-threshold colonic resection seems justified.

PMID- 14707392
TI  - Early and long-term results of surgery for severe necrotising pancreatitis.
AB  - BACKGROUND: Necrotising pancreatitis is a challenging problem for the surgeon, as
      it is associated with considerable morbidity and mortality. The indications,
      timing of surgical intervention and type of procedure continue to be debated in
      an effort to improve the outcome of this devastating disease process. METHODS: A
      retrospective analysis of early and long-term results in a series of 44
      consecutive patients (34 men, 10 women, median age 46.5, range 13-74 years) who
      underwent necrosectomy for severe necrotising pancreatitis. In 16 patients
      necrosectomy and primary abdominal closure with drains was performed, 14 patients
      had planned staged necrosectomy and delayed abdominal closure with drains, and in
      14 patients necrosectomy with open laparostomy was undertaken. RESULTS: There
      were 8 deaths (18%) and 14 cases (32%) of significant hospital morbidity (fistula
      10, pseudocyst 2, renal failure 2). Variables which correlated with mortality
      were: high APACHE II score, acute renal failure requiring dialysis, and
      requirement for surgical intervention at an early stage (within the first two
      weeks). A total of 28 late complications occurred in 21 of the surviving patients
      (endocrine pancreatic insufficiency 10, exocrine pancreatic insufficiency 2,
      pseudocyst 2, chronic renal failure 2, incisional hernia 10, recurrent
      pancreatitis 1, and chronic pain 1). CONCLUSIONS: Low mortality can be achieved
      in patients with severe necrotizing pancreatitis with aggressive surgical
      intervention and careful perioperative management. Long-term morbidity remains
      high, and emphasises the need for prolonged follow-up.

PMID- 14707393
TI  - Outcomes and indications of segmental pancreatectomy. Comparison with distal
      pancreatectomy.
AB  - BACKGROUND/AIM: To preserve pancreatic function, segmental pancreatectomy has
      been proposed for benign or low-malignancy tumors in the pancreatic body.
      Indications for the procedure, however, are still controversial. METHODS: In this
      study, we investigated the advantages and disadvantages of segmental
      pancreatectomy compared with distal pancreatectomy and subsequently determined
      indications for segmental pancreatectomy. RESULTS: The distal pancreatectomy
      patients had shorter operation times, lower incidence of operative complications,
      and shorter hospital stays compared to segmental pancreatectomy patients.
      Endocrine function in distal pancreatectomy patients deteriorated compared to
      that of segmental pancreatectomy patients. The postoperative 75-gram oral glucose
      tolerance test showed a diabetic pattern in 3 of 7 distal pancreatectomy
      patients, whereas none of the segmental pancreatectomy patients became diabetic
      after surgery. The relation between the length of the removed pancreas and plasma
      glucose at 2 h after the 75-gram glucose intake showed a significant correlation.
      CONCLUSION: According to our results, if the length of removed pancreas is longer
      than 12 cm, the patients will have a risk of acquiring diabetes. In those cases,
      the segmental pancreatectomy should be considered.

PMID- 14707394
TI  - Pancreatic fistula rate after pancreatic resection. The importance of
      definitions.
AB  - BACKGROUND: Pancreatic fistula (PF) is still regarded as a serious complication
      both in terms of frequency and sequelae. The incidence varies greatly in
      different reports because of the different definitions used. The aim of this
      study was to compare several definitions of PF encountered in the current
      literature and to demonstrate that the PF rate in the same group of patients
      treated in a high volume center is dependent upon the definition applied.
      METHODS: A Medline search of the last 10 years was performed as regards the
      definition of PF. A score was assigned to the reproducible definitions based upon
      two basic parameters: daily output (cm3) and duration of the fistula represented
      by the number of days between the postoperative day of onset and the duration of
      the complication. Four definitions were formulated and were then applied to a
      group of 242 patients that underwent pancreatic head or intermediate resections
      with pancreatico-jejunal anastomosis in our Pancreatic Unit between November 1996
      and December 2000. Statistical analysis was carried out using the Yates correct
      chi2 test with statistical significance set at p < 0.05. RESULTS: Among 26
      different definitions identified, 14 were found suitable for the applied score.
      We formulated four final definitions summarizing the current concepts of PF. The
      incidence of PF ranged between 9.9 and 28.5% according to the different
      definitions applied with highly statistical differences between them.
      CONCLUSIONS: The PF rate after pancreatic resections is strictly dependent upon
      the definition used. An overall general agreement for an internationally accepted
      definition is urgently needed to correctly compare different experiences.

PMID- 14707395
TI  - Endoscopic management of common bile duct stones leaving the gallbladder in situ.
      A cohort study with long-term follow-up.
AB  - BACKGROUND: Obstructive jaundice caused by stones is a common disorder, mostly
      managed by endoscopic sphincterotomy followed by cholecystectomy. The aim of this
      study was to evaluate whether or not clearance of the common bile duct alone is
      sufficient as treatment for patients with choledocholithiasis. METHODS: A cohort
      with 447 patients with symptomatic cholecystocholedocholithiasis, undergoing
      endoscopic retrograde cholangiography (ERC) and if necessary sphincterotomy (ES).
      In 164 patients common bile duct stones were proven and treated endoscopically,
      without performing a subsequent cholecystectomy. All 164 patients were free of
      symptoms after the endoscopic intervention. This group of patients was compared
      with 78 patients who underwent cholecystectomy after endoscopic treatment of
      common bile duct stones. Patients were followed for 1-13 years after ERC and
      sphincterotomy results and complications were registered. RESULTS: The ages of
      the 164 patients in the in situ group were significantly higher than in the
      cholecystectomy group and the ASA classification (American Society of
      Anesthesiologists) was significantly higher in the in situ patients. Mean follow
      up was 70.9 months. Of the in situ patients 27 (16%) returned with biliary
      symptoms; 12 with common bile duct stones, three with cholangitis, and one with
      stenosis of Vater's papilla. Eight patients returned with cholecystitis and 3
      with symptomatic cholecystolithiasis. Thirteen patients underwent cholecystectomy
      and 11 were managed (also) endoscopically. Minor complications were 2 wound
      infections and 1 bleeding after cholecystectomy. Two patients (1%) died of
      abdominal sepsis due to cholecystitis. Of the patients who underwent
      cholecystectomy, 6 (7.6%) returned during follow-up. Three patients had common
      bile duct stones, 2 had cholangitis and 1 patient presented with papillostenosis.
      Three patients needed surgical common bile duct exploration and the other 3 were
      treated endoscopically. After reintervention, cardiopulmonary complications were
      observed in 1 patient. There was no related death. CONCLUSION: When common bile
      duct stones are treated successfully by endoscopic sphincterotomy and patients
      are free of symptoms, there is no need for routine prophylactic cholecystectomy.

PMID- 14707396
TI  - Efficacy and tolerability of pantoprazole compared with misoprostol for the
      prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic
      patients.
AB  - AIM: To compare the efficacy and tolerability of pantoprazole 20 mg once daily
      (o.d.) with misoprostol 200 microg twice daily (b.i.d.), administered for 6
      months to rheumatic patients who required long-term therapy with nonsteroidal
      anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing
      gastrointestinal lesions. METHODS: This randomized, double-blind, multicenter,
      parallel group comparison study was performed with rheumatic patients (n = 515)
      who were likely to take NSAIDs continuously for at least 6 months. Patients were
      55 years or older, at risk to develop gastrointestinal lesions, had less than
      five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux
      esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate
      intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not
      available at the time). Patients were randomized to take either pantoprazole 20
      mg o.d. (n = 257) or misoprostol 200 microg b.i.d. (n = 258) for 6 months while
      continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months.
      RESULTS: Pantoprazole was superior to misoprostol (p < 0.001) with regard to
      'therapeutic failure' (occurrence of a peptic ulcer, ten or more
      erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe
      gastrointestinal symptoms, and/or 'likely' or 'definitely' related adverse event
      leading to study termination). Estimated remission rates at 3 and 6 months
      (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole)
      and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p =
      0.005) with regard to 'endoscopic failure' (occurrence of a peptic ulcer, ten or
      more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6
      months. Estimated remission rates at 3 and 6 months were, respectively, 98 and
      95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study
      early due to adverse events 'likely' or 'definitely' related to the study drug
      accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol
      treatment groups. CONCLUSION: Pantoprazole 20 mg o.d. is superior to misoprostol
      200 microg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and
      symptoms in patients on continuous long-term treatment with NSAIDs due to
      rheumatic diseases and at risk to develop such lesions or symptoms.

PMID- 14707397
TI  - Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A
      randomized, placebo-controlled study.
AB  - BACKGROUND: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective
      effect against colon cancer. To explain this, a reduced proliferation of the
      colorectal mucosal proliferation was suggested. We, therefore, examined the
      influence of UDCA on the proliferation of normal colorectal mucosa in humans.
      METHODS: Following endoscopic polypectomy, 20 patients with colorectal adenomas
      were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo
      (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were
      sampled before and at the end of the medication by total colonoscopy. Colorectal
      mucosal proliferation was measured by FACScan analysis of propidium iodine
      labeling. Serum was sampled, and serum bile acids were analyzed by gas
      chromatography. RESULTS: The proliferation rates at the end of the study were
      similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%,
      14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the
      study were significantly higher in group A (1.3 micromol/l, 0.9-1.8) than in
      group B (0.7 micromol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels
      were similar in both groups. CONCLUSIONS: In this study, UDCA treatment for 6
      months does not seem to induce changes in the proliferative behavior of the
      colorectal mucosa in patients with adenomas. It seems likely that a putative
      chemopreventive effect of UDCA in humans is not exerted by a reduction of the
      colorectal proliferation.

PMID- 14707398
TI  - Effects of acute wound environment on neonatal rat dermal multipotent cells.
AB  - Dermal multipotent cells (DMCs) with the capacity to differentiate to osteocytes,
      chondrocytes, adipocytes and neurons were isolated from the dermis of newborn
      Wistar rats by their adherence to culture plastic dishes. After labeling with a
      fluorescent nuclear marker, 4',6-diamidino-2-phenylindole, neonatal DMCs were
      implanted into minced skin. The labeled cells were found in the regenerative skin
      2 weeks after implantation. Topical transplantation of DMC suspension on full
      thickness excision wounds made on the back of female rats enhanced the initial
      rate of contraction. Wound fluid collected using polyvinyl alcohol sponges from
      the incisions on the dorsa of adult rats on day 3 postwounding was used in the
      experiments. A methylthiazolyldiphenyl tetrazolium bromide assay showed that
      wound fluid with concentrations from 5 to 30% induced an increase in the number
      of cultured DMCs. The wound model of a monolayer of cells indicated that 10%
      wound fluid accelerated the migration rate of DMCs to fill in defects made in the
      layer of cultured cells. A colorimetric analysis also indicated that 10% wound
      fluid increased the hydroxyproline content in cultured cells. In conclusion, DMCs
      have been isolated from newborn rat dermis by their adherence to culture plastic
      dishes, and acute wound environment in the early stage promotes the viability,
      migration and collagen synthesis of these cells.

PMID- 14707399
TI  - Fourier transform infrared spectroscopy application to vascular biology:
      comparative analysis of human internal mammary artery and saphenous vein wall.
AB  - Saphenous vein (SV) and internal mammary artery (IMA) are used for aorto-coronary
      bypass grafting. IMA is considered to be the graft of choice for coronary
      revascularization having a long-term patency compared to SV. The aim of this
      study is to investigate the structure of vascular wall using a new technical
      approach. We analysed the chemical composition of vessel wall layers (total
      lipid, lipid ester and protein) of 25 vascular segments (19 SV and 6 IMA) using
      Fourier transform infrared spectroscopy (FTIR). FTIR analysis showed that in
      intima layer lipid ester and protein concentration (expressed as arbitrary units)
      was significantly higher in SV (lipid ester = 0.020 +/- 0.002; protein = 0.449 +/
      0.022) than in IMA (lipid ester = 0.014 +/- 0.002; protein = 0.342 +/- 0.032).
      Moreover, the percentage of lipid ester on total lipid was significantly higher
      in SV (intima = 54.7 +/- 2.9%; media = 78.4 +/- 4.9%; adventitia = 83.9 +/- 8.3%)
      wall layers compared to IMA ones (intima = 37.3 +/- 4.9%; media = 45.4 +/- 3.8;
      adventitia = 57.1 +/- 4.8). These data suggest that a different chemical
      composition of wall layers could also be responsible for the morphological
      modifications observed in SV after grafting.

PMID- 14707400
TI  - Development of lymphoid tissues of the stripe-faced dunnart (Sminthopsis
      macroura).
AB  - The development of the lymphoid tissues of a model marsupial, the stripe-faced
      dunnart, has been described from birth to weaning, a period of 2.5 months. At
      birth the lymphoid tissues, including the thymus, lymph nodes and mucosa
      associated lymphoid tissues, were undeveloped. A thoracic thymus consisting
      primarily of stromal tissue was observed by day 4 after birth but by day 12,
      lymphocytes were observed in the thymus and some cortico-medullary
      differentiation was apparent. Lymph nodes were histologically mature by day 31,
      the earliest day investigated for this tissue. In gut tissue, lymphoid follicles
      were first observed by day 57 post-partum. No bronchus-associated lymphoid tissue
      was observed in any lung samples. The thymus, lymph nodes and gut-associated
      lymphoid tissues were all distinguishable before weaning (day 70) but not all
      were histologically mature. The sequence of development of the lymphoid tissues
      in the stripe-faced dunnart was similar to those observed in other marsupial
      species.

PMID- 14707401
TI  - The ramifications and terminals of optic fibres in layers 2 and 3 of the avian
      optic tectum: a golgi and light and electron microscopic anterograde tracer
      study.
AB  - The ramification patterns and terminals of optic fibres in layers 2 and 3 of the
      optic tectum were studied in Golgi-stained and immunolabelled preparations made
      from the brains of chicks and pigeons. The different neuronal structures of
      layers 2 and 3 were also examined. In Golgi preparations, two types of optic
      fibre were found both in chick and pigeon tectum according to their thickness and
      terminal branching patterns. The same types of optic fibres were also found to be
      present in the anterograde tracer experiments after iontophoresis of biotinylated
      dextran amine into the optic nerve. The varicose terminals of thin fibres mostly
      terminated on terminal dendritic sections of radiate and pyramidal-like neurons,
      contacting them on their apical dendrites. The medium-thick fibre terminals in
      layer 2 mainly established synapses with horizontally extending dendrites, which
      may therefore be contacts with inhibitory local circuit neurons. The medium-thick
      optic fibre bushy-like arborisation in layer 3 established synapses with larger
      dendrites and also stem dendrites. Their terminals formed groups with different
      dendritic profiles, some of which were partly covered by glial processes, and/or
      were located among converging dendrites. The presence of these glomerular-like
      synapses in layer 3 proves that the optic terminals in layer 3 also take part in
      the transmission of optic impulses to the nucleus rotundus.

PMID- 14707402
TI  - Orbital passage of pterygopalatine ganglion efferents to paranasal sinuses and
      nasal mucosa in man.
AB  - Parasympathetic nerves of pterygopalatine ganglion origin are considered to enter
      the orbit and distribute to the nasal mucosa with the anterior ethmoidal nerve.
      As their distribution has never been demonstrated the present study was
      undertaken to seek evidence of their passage and to identify their relationship
      with the ethmoidal nerves. The soft tissues of the pterygopalatine fossa and
      orbit from sixteen sides of twelve cadavers were removed in one piece and either
      dissected or cut coronally into slabs and prepared histologically using montages
      of thin resin-embedded sections at intervals suitable for nerve path tracing.
      Several of the rami orbitales passing mediodorsally from the ganglion enter the
      orbit apically, branch and enter the posterior ethmoidal foramen terminating in
      the lining of the paranasal sinuses and others advance to enter the anterior
      ethmoidal canal to reach the nasal mucosa. No junctions were made with ethmoidal
      nerves within the orbit or the canal. Failure of surgical lesions of the anterior
      ethmoidal nerve as a treatment for vasomotor rhinitis may be attributed to the
      sparing of the separate parasympathetic nerves. Appropriate chemical lesions, on
      the other hand, could ensure destruction of isolated parasympathetic nerves while
      limiting damage to the larger anterior ethmoidal nerve.

PMID- 14707403
TI  - Organization of stroke care: education, referral, emergency management and
      imaging, stroke units and rehabilitation. European Stroke Initiative.

PMID- 14707404
TI  - Prevention. European Stroke Initiative.

PMID- 14707405
TI  - Acute treatment of ischaemic stroke. European Stroke Initiative.

PMID- 14707406
TI  - Recanalization of cervical artery dissection: influencing factors and role in
      neurological outcome.
AB  - BACKGROUND AND PURPOSE: Generally, the prognosis for cervical artery dissection
      (CAD) is uncertain. The recanalization rate of CAD can be up to 85% within 3
      months. This study evaluates the variables that might affect recanalization and
      the role of recanalization as a predictor for neurological outcome. PATIENTS AND
      RESULTS: This study prospectively included 38 patients with acute stroke
      following occlusion due to CAD (18 males, 20 females, median age 50.5 years,
      range 16-82). Vertebral and carotid dissections were equally distributed (19
      carotid dissections). The recanalization rate was influenced by the presence of
      hypertension (p = 0.001). Outcomes were dependent on infarct location. Patients
      with lateral medullary infarction returned to functional independence (p =
      0.026), while patients with deep hemispheric infarction tended to have a
      disabling stroke (p = 0.068). The presence of good collaterals seemed to
      influence functional independence (p = 0.03). CONCLUSION: There seemed to be no
      relationship between outcome and the rate of recanalization following CAD.
      Recanalization appeared to be a spontaneous mechanism, which could have depended
      on the intrinsic condition of the vessels. Finally, neurological outcome was
      dependent on lesion localization and the presence of good collaterals.

PMID- 14707407
TI  - Incidence, etiology, and outcome of stroke in patients on continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND: Little information exists on clinical features of stroke in patients
      receiving continuous ambulatory peritoneal dialysis (CAPD). The goals of this
      study was to clarify features of stroke in CAPD patients, to determine factors to
      predict onset of stroke during chronic CAPD, and to determine whether CAPD had an
      advantage over hemodialysis (HD) for prevention of stroke. METHODS: We determined
      features of stroke in 12 patients (14 attacks including 7 parenchymal and 1
      subarachnoid hemorrhage and 6 infarction) among 188 consecutive patients on CAPD,
      and compared them with those of 137 stroke patients among 1,681 consecutive
      patients on hemodialysis. RESULTS: Incidence of stroke for CAPD patients (15.7
      per 1,000 person-years) was high compared with that of HD patients (approximately
      12) or general residents in our suburban town. Patients with stroke on CAPD were
      younger than those on HD (52 +/- 12 vs. 62 +/- 11 years, p = 0.008). Mean
      arterial pressure (MAP) of patients with stroke increased after the introduction
      of CAPD (p = 0.01), whereas that of patients without stroke did not change.
      Increase in MAP during chronic CAPD was related independently to the occurrence
      of total stroke or brain hemorrhage. The majority of CAPD patients with stroke
      (67%) were dead or dependent in the chronic stage of stroke. CONCLUSION: CAPD
      patients seem to have a greater risk of stroke than the general population
      primarily because of poor control of hypertension, presumably in part due to
      overhydration. CAPD does not seem to have an advantage over HD for the prevention
      of stroke.

PMID- 14707408
TI  - Transoral carotid ultrasonography as a diagnostic aid in patients with severe
      carotid stenosis.
AB  - Evaluation of the distal portion of the extracranial internal carotid artery
      (ICA) is indispensable for the judgment of whether surgical treatment for high
      grade carotid stenosis is preferable or not. When the ICA is occluded or severely
      stenosed by an organic lesion along the long segment, carotid endarterectomy
      (CEA) is abandoned. On the other hand, CEA may be beneficial in patients with
      severe carotid stenosis which is situated only in the restricted lesion of the
      proximal portion of the ICA. Conventional carotid ultrasonography sometimes
      cannot provide sufficient information due to calcified plaque and/or high
      position of bifurcation. Newly developed transoral carotid ultrasonography (TOCU)
      enables us to observe the distal extracranial ICA and distinguish the
      differential diagnosis. We herein report 3 cases of severe carotid stenosis in
      which TOCU provided the necessary information obtained neither by conventional
      carotid ultrasonography nor by angiogram. We concluded that TOCU provides
      prerequisite information in certain cases in which CEA is considered.

PMID- 14707409
TI  - How a sequential design would have affected the GAIN International Study of
      gavestinel in stroke.
AB  - While planning the GAIN International Study of gavestinel in acute stroke, a
      sequential triangular test was proposed but not implemented. Before the trial
      commenced it was agreed to evaluate the sequential design retrospectively to
      evaluate the differences in the resulting analyses, trial durations and sample
      sizes in order to assess the potential of sequential procedures for future stroke
      trials. This paper presents four sequential reconstructions of the GAIN study
      made under various scenarios. For the data as observed, the sequential design
      would have reduced the trial sample size by 234 patients and shortened its
      duration by 3 or 4 months. Had the study not achieved a recruitment rate that far
      exceeded expectation, the advantages of the sequential design would have been
      much greater. Sequential designs appear to be an attractive option for trials in
      stroke.

PMID- 14707410
TI  - Acetylsalicylic acid and acetaminophen to combat elevated body temperature in
      acute ischemic stroke.
AB  - BACKGROUND: Because elevated body temperature (BT) in acute ischemic stroke is
      associated with poor outcome, it is currently recommended to maintain
      normothermia with antipyretics. Whether this can be achieved by the
      administration of acetylsalicylic acid (ASA) or acetaminophen is uncertain.
      METHODS: Over a period of 9 months, patients admitted with acute hemiparetic
      ischemic stroke were monitored for BT in the first 48 h. When BT rose >37.5
      degrees C, patients were treated with either ASA 500 mg intravenously or
      acetaminophen suppository 1,000 mg. When 6 h later the BT was still or again
      >37.5 degrees C, patients were further treated with acetaminophen suppository
      1,000 mg up to 4 times a day. Primary outcome measure was normothermia (BT
      </=37.5 degrees C) within respectively 1 and 3 h after intervention. Secondary
      outcome parameters were any decrease in BT and the mean decrease in BT. RESULTS:
      Of a total of 132 patients, 63 (48%) developed a BT >37.5 degrees C. The effects
      of 43 injections of ASA and 89 administrations of acetaminophen were studied.
      After 1 h, treatment with acetaminophen produced both significantly more
      reductions in BT and normothermia (respectively in 60 and 20%) than treatment
      with ASA (respectively in 37 and 5%). At 3 h, both interventions had a similar
      effect, with normothermia being achieved in only 37-38%. Fever (>38.0 degrees C)
      and evidence of an infection were related to unresponsiveness to treatment.
      CONCLUSIONS: In the majority of patients with acute ischemic stroke, ASA and
      acetaminophen are insufficient for reducing an elevated BT to a state of
      normothermia.

PMID- 14707411
TI  - High intensity transient signals in patients with carotid stenosis may persist
      after carotid endarterectomy.
AB  - BACKGROUND: This study was undertaken to elucidate the natural history of high
      intensity transient signals (HITS) after carotid endarterectomy (CEA) and to
      determine whether this differs between patients with and without HITS detected
      preoperatively. METHODS: A 30-min transcranial Doppler (TCD) recording was
      performed to detect HITS in 141 patients at 0-1 h, 2-3 h, 4-6 h and 24-36 h
      following CEA. 104 of these patients also had 30-min TCD monitoring within 48 h
      prior to CEA. RESULTS: In the preoperative HITS-negative group, the proportion
      with postoperative HITS fell from 53% at 0-1 h to 17% at 24-36 h. In the
      preoperative HITS-positive group, the proportion with postoperative HITS remained
      steady (43% at 0-1 h, 52% at 24-36 h). During the 24-36 h postoperative epoch, 11
      of 21 (52%) of the preoperative HITS-positive group had at least one HITS
      compared to 11 of 66 (17%) of the preoperative HITS-negative group (p = 0.001).
      In a multiple logistic regression analysis, preoperative HITS was the only factor
      associated with persistent postoperative HITS. CONCLUSION: The proportion of
      cases with postoperative HITS diminished in the 24-36 h after CEA except for
      preoperative HITS-positive patients. About half of our patients undergoing CEA
      with preoperative HITS might have another embolic source.

PMID- 14707412
TI  - L-arginine-mediated vasoreactivity in patients with a risk of stroke.
AB  - OBJECTIVES: L-arginine is the substrate for nitric oxide (NO) production and has
      been shown to induce an endothelium-dependent increase in cerebral blood flow in
      humans. We studied the hypothesis that L-arginine-mediated vasoreactivity is
      impaired in patients with cardiovascular risk factors and a risk of stroke.
      METHODS: 55 patients with cardiovascular risk factors (mean age 63.0 +/- 8.5
      years) were included in the study. 45 of them had a history of previous minor
      stroke or transient ischemic attack (TIA) while 10 patients had cardiovascular
      risk factors but no previous cerebral ischemic event. Endothelium-dependent
      changes in cerebral blood flow during the infusion of 30 g L-arginine were
      assessed by continuous transcranial Doppler sonography of both middle cerebral
      arteries, intima-media thickness (IMT) of the common carotid artery, by Duplex
      sonography. Associations between risk factors, IMT, L-arginine reactivity and
      previous cerebrovascular events were analyzed by stepwise multiple linear
      regression analysis and patient groups were compared. RESULTS: Normal young
      volunteers showed an L-arginine-mediated increase in mean flow velocity of 22 +/-
      8%; L-arginine reactivity of the 55 patients was 28 +/- 10%. Patients with a
      history of stroke or TIA had significantly higher flow velocity responses to L
      arginine (29 +/- 10%) than patients with cardiovascular risk factors but no
      previous cerebrovascular event (21 +/- 8%, p < 0.05). Stepwise multiple linear
      regression analysis showed a significant association of enhanced L-arginine
      reactivity with previous stroke/TIA (p < 0.001) and elevated fibrinogen levels (p
      < 0.05) but not with age, IMT, hypertension, cholesterol or other risk factors.
      The same regression model showed an association between IMT and previous
      stroke/TIA (p < 0.001) and serum cholesterol levels (p < 0.05) but not L-arginine
      reactivity. CONCLUSIONS: L-arginine reactivity of the cerebral vessels may be
      assessed by Doppler sonography and was enhanced in patients with a history of
      stroke or TIA. It was independent of IMT of the carotid arteries. We conclude
      that enhanced L-arginine reactivity is a potential marker for cerebral
      endothelial dysfunction and an independent indicator for an increased risk of
      stroke.

PMID- 14707413
TI  - Costs of stroke care according to handicap levels and stroke subtypes.
AB  - BACKGROUND: If new advances in stroke management are to be put into practice,
      crucial information about their costs needs to be considered in relation to
      clinically pertinent variables (e.g. handicap level and stroke subtypes). Details
      of costs throughout the entire period of stroke care are essential in the
      political decision-making process, in order to avoid other budget-balancing
      approaches, which are not always satisfactory. Our aim was to perform an in-depth
      evaluation of the direct medical cost of stroke care in a large cohort. METHODS:
      We included 435 consecutive patients with brain infarction in 12 primary-care and
      referral neurology departments. Information on acute care was prospectively
      collected. Information on postacute care was collected by research nurses' visits
      to the patient's or a relative's home 18-40 months after the stroke onset. We
      thus collected detailed information on handicap levels, stroke subtypes, acute
      hospitalization costs, rehabilitation, nursing care and ambulatory costs. This
      enabled us to calculate costs over an 18-month period after the initial acute
      hospital discharge. RESULTS: By the 12th month after discharge, the costs
      amounted to 17,799 euros (16,440-19,158) per patient; the initial hospitalization
      accounted for 42% of this cost, rehabilitation for 29% and ambulatory care for
      8%. These costs were mostly concentrated within the first 3- to 6-month period.
      After 46 months without recurrence, the cost of ambulatory care outweighed the
      cost of the first 6 months. Handicap levels explained 43% of the variance of
      costs (p < 0.0001) and, according to the Rankin scale divided into 3 classes (0
      2, 3 and 4-5), cumulative costs over time differed considerably. Stroke subtypes
      were not discriminating variables except for lacunar strokes, which were
      significantly less costly than the other groups. CONCLUSIONS: By providing a
      fairly comprehensive figure for the details of direct costs of stroke care over
      time, our study gives some clues about the economic burden of stroke care which
      is mostly driven by a high handicap level. This suggests that any early
      intervention aimed at reducing the handicap level will probably dramatically
      reduce this burden.

PMID- 14707414
TI  - Development and validation of NEWSQOL, the Newcastle Stroke-Specific Quality of
      Life Measure.
AB  - BACKGROUND: A review of stroke-specific quality of life (QOL) measures indicated
      little evidence of their validity/reliability. PURPOSE: To describe the
      development/validation of a new measure - the Newcastle Stroke-Specific Quality
      of Life Measure (NEWSQOL). METHODS: Phase I: qualitative interviews (28 stroke
      patients) determined QOL issues for inclusion in the measure. Initial
      items/response categories were pre-tested (30 patients). Administration of the
      NEWSQOL in the item reduction stage (100 patients) identified poorly performing
      items and factor analysis showed likely domains. Internal consistency was
      examined. Phase II: NEWSQOL and comparator measures were administered (106
      patients) to examine validity/test-retest reliability. RESULTS: Phase I: 140
      items were identified for initial inclusion. Qualitative pre-testing led to an
      extensive revision. Item reduction resulted in a final measure of 56 items in 11
      domains (feelings, activities of daily living/self-care, cognition, mobility,
      emotion, sleep, interpersonal relationships, communication, pain/sensation,
      vision, fatigue; Cronbach's alpha = 0.71-0.90). Phase II: NEWSQOL domain scores,
      except cognition, were moderately/highly correlated (0.45-0.76) with relevant
      comparator measures. NEWSQOL domains feelings, communication and cognition
      low/moderately correlated with Barthel Index scores (-0.49 to -0.28), as
      predicted. Test-retest reliability was high (intraclass correlation coefficient
      range 0.78-0.92). CONCLUSIONS: NEWSQOL is an acceptable, patient-derived,
      interviewer-administered, stroke-specific QOL measure with evidence of
      reliability and validity, making it a promising instrument for assessing QOL
      after stroke. Involvement of relevant patients in determining the content and
      format considerably enhances confidence in its validity.

PMID- 14707415
TI  - Hyperhomocysteinemia and other newly recognized inherited coagulation disorders
      (factor V Leiden and prothrombin gene mutation) in patients with idiopathic
      cerebral vein thrombosis.
AB  - BACKGROUND: Idiopathic cerebral vein thrombosis (iCVT) represents approximately
      30% of the cases of cerebral vein thrombosis (CVT). New, inherited - factor V
      Leiden (FVL) and prothrombin gene mutation (PTHRA20210) - and inherited/acquired 
      hyperhomocysteinemia (HHcy) - prothrombotic conditions have been detected
      recently. METHODS: We assessed fasting plasma homocysteine (Hcy) levels and main
      Hcy determinants, FVL and PTHRA(20210) in 30 patients with documented iCVT and 40
      age- and sex-matched healthy subjects. RESULTS: A strong and significant
      association of PTHRA(20210) [30% (9/30) vs. 2.5% (1/40) iCVT vs. controls,
      respectively, p = 0.001; OR = 16.174, p = 0.002] and HHcy [13/30 (43.3%) vs. 4/40
      (10%) iCVT vs. controls, respectively; p = 0.002, OR = 6.88, p = 0.002] with iCVT
      was found. CONCLUSIONS: PTHRA(20210) and HHcy should be considered when screening
      for thrombophilia and should be assessed in patients with a family or personal
      history of CVT.

PMID- 14707416
TI  - Angioplasty and stenting for high-grade internal carotid artery stenosis: safety
      study in 39 selected patients.
AB  - BACKGROUND: Carotid angioplasty and stenting (CAS) is sometimes used as an
      alternative to surgery, despite the lack of evidence for its safety and efficacy.
      METHOD: Over a 33-month period, 39 consecutive patients with a stenosis >/=70%
      underwent CAS (4 in a randomized trial and 35 because of contra-indications for
      surgery). RESULTS: In 5 patients (13%; 95% CI: 3-23), a major complication
      occurred (3 disabling ischaemic strokes, 1 myocardial infarction, 1 acute
      interstitial nephropathy). In 7 patients (18%; 95% CI: 6-30), a minor
      complication occurred (5 transient ischaemic attacks, 1 transient confusional
      state, 1 non-disabling ischaemic stroke). CONCLUSION: CAS cannot be considered as
      a routine procedure and should be restricted to high-risk patients unfit for
      surgery.

PMID- 14707417
TI  - Plaque volume measurement by magnetic resonance imaging as an index of remodeling
      of middle cerebral artery: correlation with transcranial color Doppler and
      magnetic resonance angiography.
AB  - BACKGROUND: The feasibility of a noninvasive evaluation of remodeling of the
      middle cerebral artery (MCA) by magnetic resonance imaging (MRI) was assessed.
      The results were correlated with magnetic resonance angiography (MRA) and
      transcranial color Doppler (TCD) findings. METHODS: 26 patients (13 male and 13
      female, age ranged from 46 to 82 years) who presented with symptoms of
      cerebrovascular accidents had TCD, MRA and MRI assessment of the MCA. The TCD and
      MRA findings of 40 MCAs accessible by TCD were correlated with the ratio of cross
      sectional area of the vessel (VA), luminal area of the vessel (LA) and plaque
      load (PL). RESULTS: The VA ratio and LA showed no correlation with TCD or MRA
      results. PL however was shown to be associated with both TCD and MRA.
      CONCLUSIONS: MRI could be used to assess remodeling in MCAs. PL was found to be
      associated with TCD and MRA findings.

PMID- 14707418
TI  - Impairment of endothelial function in patients with spontaneous cervical artery
      dissection: evidence for a general arterial wall disease.
AB  - BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) accounts for 10-20% of
      ischemic strokes in young adults. Although trauma and preexisting disorders of
      the arterial wall are the main predisposing factors, most CADs are considered
      'spontaneous'. We hypothesized that CAD could originate in systemic vascular
      disease bound to the intima-media interface without clinical signs. If this
      hypothesis is true, endothelium-dependent vasodilation would be impaired in
      response to a physiological stimulus such as an increase in blood flow. METHODS:
      Flow-mediated arterial dilation was studied in 65 consecutive patients with
      spontaneous CAD: 26 with carotid artery dissection (ICAD), and 39 with vertebral
      artery dissection (VAD). CAD patients with vascular risk factors, trivial or
      obvious cervical trauma, or connective tissue disease were excluded. Twenty-three
      patients with ischemic stroke of unknown cause were included as controls. Using
      high-resolution ultrasonography, brachial artery diameter was measured at rest,
      during post-ischemic hyperemia (flow-mediated endothelium-dependent dilation),
      and after sublingual glyceryl trinitrate spray (endothelium-independent
      dilation). RESULTS: The mean +/- SD values of the flow-mediated vasodilation
      index were 5.7 +/- 6.2% in ICAD, 5.0 +/- 9.3% in VAD and 13.2 +/- 6.5% in
      controls (p < 0.0005), without any difference between ICAD and VAD. Endothelium
      independent dilation mean values were 21.5 +/- 9.5% in ICAD, 25.1 +/- 12.5% in
      VAD, and 20.8 +/- 8.4% in controls, without a significant difference between
      groups (p = 0.49). CONCLUSIONS: These results give evidence of impaired
      endothelium-dependent vasodilation in CAD patients that is not the result of
      stroke, and suggest that an underlying abnormality of the arterial wall layers
      may predispose to CAD.

PMID- 14707419
TI  - Changes in cardiac thrombus status after cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Intracardiac thrombi are a potential source of cerebral
      embolism. The disposition of intracardiac thrombi in ischemic stroke/transient
      ischemic attack (TIA) patients was investigated over a 10-month period using
      omniplanar transesophageal echocardiography (TEE). METHODS: One hundred and five
      patients underwent TEE examination at <1 month and again at 9-12 months (mean 10
      months) after symptom onset. TEEs were evaluated for thrombi in the left atrium,
      left atrial appendage and left ventricle. Stroke risk factors and TEE findings
      were compared between patients with and without new thrombi on follow-up TEE.
      Similar comparisons were made in patients with and without disappearance of
      thrombi on the follow-up TEE. The effect of anticoagulants was evaluated.
      RESULTS: Intracardiac thrombi were found initially in 18% (95% CI 11-25%) of
      patients in 79% (95% CI 61-97%) of whom the thrombi disappeared on the follow-up
      TEE; this significantly correlated with warfarin anticoagulation (p = 0.037). In
      the remainder 82% (95% CI 75-89%) patients, new thrombi were detected on the
      follow-up TEE in 8% (2-14%). These were older (p = 0.009), and not on
      anticoagulation. Patients with aortic atheroma >/=4 mm were also more likely to
      develop new intracardiac thrombi (p = 0.001). CONCLUSIONS: Anticoagulation with
      warfarin for 10 months is associated with conditions leading to disappearance of
      intracardiac thrombi after a cerebral ischemic event and hence has a probable
      therapeutic role. Older patients, not anticoagulated, and those with significant
      aortic atheroma >/=4 mm may have increased probability for de novo thrombus
      development. These patients may be at risk of cardiac embolization and could be
      considered for prophylactic anticoagulation.

PMID- 14707420
TI  - Hyperdense middle cerebral artery sign: can it be used to select intra-arterial
      versus intravenous thrombolysis in acute ischemic stroke?
AB  - BACKGROUND: Stroke patients with a hyperdense middle cerebral artery sign (HMCAS)
      may respond less favorably to intravenous (IV) thrombolysis. OBJECTIVE: To
      compare outcomes of patients with and without early CT findings treated with IV
      versus intra-arterial (IA) recombinant tissue plasminogen activator (rtPA).
      METHODS: Initial and 24-hour CT scans of the head were evaluated in 83
      consecutive stroke patients (66 on IV rtPA, 17 on IA rtPA). Time permitting, a CT
      angiogram was performed immediately after the initial CT scan to ascertain major
      cerebral artery occlusion. Demographics and etiological stroke subtype, times to
      thrombolysis and CT scan, baseline (prethrombolysis) and 24-hour National
      Institutes of Health stroke scale (NIHSS) score, discharge NIHSS score and 90-day
      modified Rankin scale (mRS) were recorded. The initial CT of these patients was
      examined for early signs of stroke. The 24-hour scan was reviewed for the
      presence of infarct, hemorrhage and persistence of HCMAS. RESULTS: A favorable
      outcome, indicated by a significant improvement in the discharge NIHSS score, was
      noted with IA rtPA, irrespective of the presence (p = 0.001) or absence (p =
      0.01) of HCMAS. A less favorable outcome in discharge NIHSS score was noted with
      IV rtPA in patients with HCMAS (p = not significant) than those without the sign
      (p < 0.001). A similar proportion of patients with HCMAS exhibited a neurological
      improvement at 24 h as those without the sign in the IA rtPA group (p = 0.9).
      However, a smaller proportion of patients with HCMAS exhibited a neurological
      improvement at 24 h than those without the sign in the IV rtPA group (p = 0.005).
      The results were similar using 90-day mRS </=1 as an indicator of significant
      persistent improvement (p = 1.0 for IA rtPA and 0.04 for IV rtPA group).
      CONCLUSIONS: In a small sample, patients with HMCAS appeared to respond better to
      IA than IV rtPA.

PMID- 14707421
TI  - Right-to-left-shunts detected by transesophageal echocardiography and
      transcranial Doppler sonography.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) and transcranial Doppler
      sonography (TCD) can identify right-to-left-shunts that predispose to paradoxical
      embolism. In a large cohort we compared the results of both techniques. METHODS:
      222 patients were investigated by both techniques using the contrast agent
      Echovist-300 and performing each test once without and once with the Valsalva
      maneuver (VM). RESULTS: TEE-proven right-to-left-shunts were detected by TCD with
      a high sensitivity of 94%. In addition, TCD revealed shunts not noted during TEE
      in about 20% of all patients studied. These shunts are in general smaller than
      those concordantly identified; however, 9% of the patients without a TEE-proven
      shunt presented with a shunt that allows a considerable amount of contrast medium
      to pass. There were 12% more microbubbles detected in the right middle cerebral
      artery than in the left middle cerebral artery during the TCD test performed with
      VM, but not during the TCD test performed without VM. CONCLUSIONS: Contrast
      enhanced TEE and TCD are complementary methods in the assessment of stroke and
      stroke-prone patients. The side difference of microbubbles may indicate a
      selective streaming of cardiac emboli during VM.

PMID- 14707422
TI  - Apolipoprotein H gene polymorphisms and risk of primary cerebral hemorrhage in a
      Chinese population.
AB  - BACKGROUND AND PURPOSE: Apolipoprotein H (ApoH) has been implicated in several
      physiologic pathways including lipid metabolism, coagulation and the production
      of hypertension, which are related to the pathogenesis of primary cerebral
      hemorrhage (PICH). The gene coding for ApoH is polymorphic, with the occurrence
      of several common alleles in the general population. This genetically determined
      variation can effect lipid metabolism and the production of hypertension. We
      determined the distribution of ApoH gene polymorphisms in Chinese people and
      investigated whether these polymorphisms were associated with increased risk of
      PICH in a Chinese population. METHODS: We studied polymorphisms of the ApoH gene
      by the polymerase chain reaction-single strand conformation polymorphism
      technique and DNA sequencing in 140 PICH patients and 100 healthy control
      subjects. Serum antiphospholipid antibodies and lipid levels were also examined
      in all subjects. RESULTS: Four polymorphisms of the ApoH gene have been
      identified in Chinese people. No difference in genotype frequencies of G817T
      (Leu247Val) polymorphism, G1025C (Try316Ser) polymorphism and C1080T polymorphism
      was observed between PICH patients and control subjects (p > 0.05). The G341A
      (Ser88Asn) polymorphism correlated significantly with PICH. The frequencies of
      the A allele were significantly higher in PICH patients than in controls,
      especially in PICH patients with hypertension and a family history of stroke.
      CONCLUSIONS: Our results suggest that the G341A (Ser88Asn) polymorphism might be
      associated with increased risk of PICH in a Chinese population. The association
      appeared to be mediated by the generation of hypertension.

PMID- 14707423
TI  - Reconstituted high-density lipoprotein exhibits neuroprotection in two rat models
      of stroke.
AB  - BACKGROUND: Reconstituted high-density lipoprotein (rHDL) is prepared from
      apolipoprotein A-I, isolated from human plasma, and soybean-derived
      phosphatidylcholine and exhibits biochemical and functional characteristics
      similar to endogenous nascent high-density lipoprotein (HDL). This study tested
      the hypothesis that pretreatment with rHDL may reduce neuronal damage in 2
      experimental rat models of stroke. METHODS: In the first model, an excitotoxic
      lesion was induced by unilateral injection of N-methyl-D-aspartate (NMDA) in the
      right striatum (excitotoxic lesion model). In the second model, temporary
      occlusion of the middle cerebral artery (MCA) was attained by inserting a nylon
      thread through the carotid artery and blood flow was restored 30 min later (MCAo
      model). In both models, either rHDL (120 mg/kg) or saline (control) were infused
      over 4 h, starting 2 h before the injection of NMDA or the induction of ischemia,
      respectively. 24 h after the interventions, the rats were sacrificed and the
      brains removed for histochemical preparation. The necrotic area was delimited
      using an image analysis system. In addition, the levels of reactive oxygen
      species (ROS) in human endothelial (ECV 304) and neuroblastoma (SK-N-BE) cell
      lines were measured fluorometrically as 2',7'-dichlorofluorescein fluorescence in
      the presence and absence of rHDL and under basal and stress-induced conditions.
      RESULTS: In the excitotoxic lesion and MCAo models, pretreatment with rHDL
      significantly reduced the brain necrotic area by 61 and 76%, respectively (p <
      0.01). Overnight incubation of ECV 304 and SK-N-BE cells with 0.5 mg/ml rHDL
      decreased basal and stress-induced ROS levels by 73 and 72% (ECV 304) and by 76
      and 43% (SK-N-BE), respectively (p < 0.01). CONCLUSION: These results suggest
      that rHDL reduces neuronal damage after onset of ischemic stroke, possibly by
      involving an anti-oxidative mechanism. Thus, rHDL may be a powerful
      neuroprotective tool for the treatment of cerebrovascular diseases.

PMID- 14707424
TI  - Measurement of ankle brachial index for assessment of atherosclerosis in patients
      with stroke.
AB  - BACKGROUND: Though atherosclerosis is generally regarded as a risk factor for
      stroke, its quantitative assessment in patients with stroke has not yet been
      reported. Recently, the ankle brachial index (ABI) has been receiving increasing
      attention as a noninvasive measurement of atherosclerosis. In this study, we
      investigated ABI to determine the degree of atherosclerosis in patients with
      stroke. METHODS: ABI was measured in 114 patients who had suffered a stroke, and
      the significance of differences between the ABI of the stroke subgroups and that
      of the normal group was investigated. The correlation of ABI with the degree of
      cerebral artery stenosis was also investigated. RESULTS: There was no significant
      difference in ABI between the hemorrhagic groups and the normal group, but in the
      infarction group (p = 0.0002) ABI was significantly less than the normal group.
      ABI was significantly correlated with the degree of stenosis in the intracranial
      internal carotid artery and middle cerebral artery (p < 0.0001, respectively).
      CONCLUSIONS: A strong relationship between ischemic stroke and atherosclerosis
      was demonstrated quantitatively by ABI measurement. A decrease in ABI may be a
      risk factor for ischemic stroke.

PMID- 14707425
TI  - Reliability of the questionnaire for verifying stroke-free status.
AB  - BACKGROUND: The Questionnaire for Verifying Stroke-Free Status (QVSS) is a
      practical instrument for confirming absence of previous symptomatic stroke or
      transient ischemic attack in control subjects participating in stroke research.
      METHODS: We tested reliability of telephone administration of the QVSS in stroke
      patients and healthy volunteers aged >/=50 years. For intrarater reliability, one
      interviewer administered the QVSS twice to the same subjects 8 weeks apart (115
      subjects). For interrater reliability, one interviewer administered the QVSS and
      a different interviewer readministered the QVSS 8 weeks later (107 subjects).
      Both interviewer and interviewee were masked to responses from the first
      interview. RESULTS: Intrarater agreement for overall classification of stroke
      free status was 0.90 [95% confidence interval (CI), 0.82-0.94], with a kappa of
      0.78 (95% CI, 0.67-0.90). Interrater agreement for overall classification was
      0.94 (95% CI, 0.88-0.98), with a kappa of 0.89 (95% CI, 0.80-0.97). CONCLUSION:
      The QVSS is a reliable instrument for telephone interviews in stroke research
      when applied to adult populations without severe deficits of cognition or verbal
      communication.

PMID- 14707426
TI  - Validity and reliability of estimating the scandinavian stroke scale score from
      medical records.
AB  - BACKGROUND: Reliable estimation of severity of neurological impairments early
      after stroke is essential for research and audit of acute stroke care. Obtaining
      this information prospectively requires significant resources. We wished to
      assess the reliability of estimating the Scandinavian Stroke Scale (SSS) score
      retrospectively from routine hospital admission records. METHODS: Acute stroke
      admissions to a large urban hospital were examined and had their SSS scored by an
      experienced physician within 4 h of the examination performed by the medical
      admissions team. Two examiners (a trained research nurse and a second physician),
      blinded to the patients' clinical condition, later independently estimated
      retrospective SSS scores using information documented in the medical admission
      notes. RESULTS: Fifty patients were recruited [median age 73 years (interquartile
      range 61, 79)]. Weighted kappa statistics for agreement between domains of the
      face-to-face and retrospective SSS were as follows: consciousness 0.73, eye
      movements 0.60, arm motor power 0.83, hand motor power 0.71, leg motor power
      0.81, orientation 0.81, speech 0.80, and facial palsy 0.53. The intraclass
      correlation coefficient for face-to-face and retrospective SSS composite scores
      was 0.97 (95% CI 0.96-0.98), p < 0.0001. Interobserver reliability for the
      different components of the retrospective SSS was excellent (kappa values greater
      than 0.75) apart from consciousness (0.71) and eye movements (0.58). CONCLUSIONS:
      The composite SSS score and most of its individual components can be reliably
      estimated retrospectively from routine hospital admission records. This method is
      potentially useful both in observational studies and in case-mix adjustment for
      audit purposes.

PMID- 14707427
TI  - Relationship of lumen diameter to type and degree of arterial remodeling at sites
      of expanding wall or plaque thickness in human carotid artery.
AB  - BACKGROUND: Arterial remodeling exhibits a bidirectional capacity. Whether lumen
      size affects remodeling response to lesion change is unknown. METHODS:
      Prospective study by duplex ultrasonography over 2 years in 61 subjects with
      coronary artery disease. Direction and magnitude of vessel remodeling are
      calculated for internal carotid, bifurcation, and common carotid artery segments.
      RESULTS: A linear trend is discernible between lumen diameter and direction and
      magnitude of remodeling at sites of expanding intima-media thickness (IMT) or
      plaque. Rate of lesion change varied inversely with lesion thickness with an
      inflection between rates for low-dimension IMT and plaque. CONCLUSIONS:
      Dilatation versus shrinkage in the remodeling response to expanding lesions
      appears related to lumen size. IMT and plaque exhibit independent biologies.

PMID- 14707428
TI  - Maternal treatment with propofol attenuates lipid peroxidation after transient
      intrauterine ischemia in the neonatal rat brain.
AB  - The purpose of this study was to investigate whether propofol has a
      neuroprotective effect on the fetal brain after intrauterine ischemia-reperfusion
      (I/R) injury in the rat fetus. Fetal brain ischemia was induced by clamping the
      utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by
      removing the clamps for 2 h. A 40-mg/kg single dose of propofol was administered
      intraperitoneally 15 min before I/R injury. Lipid peroxidation in the brain
      tissue was determined as the concentration of thiobarbituric acid reactive
      substances (TBARS) for each fetal rat. Results showed that lipid peroxidation
      byproducts increased after I/R injury. Maternal treatment with propofol reduced
      TBARS compared to the I/R group. Propofol has been shown to have neuroprotective
      effects in intrauterine I/R-induced fetal brain damage in rats.

PMID- 14707429
TI  - Tibial speed of sound in term and preterm infants.
AB  - The tibial speed of sound (SOS) was measured in 91 healthy singleton infants
      between 31 and 42 weeks of gestation and 12 sick preterm infants. In healthy
      infants, the tibial SOS was associated with corrected gestational age (r = 0.40,
      p < 0.001) but not birth weight. The median tibial SOS in 12 sick preterm infants
      (2,772, range 2,566-2,934 m/s), whose corrected gestational age was between 31
      and 42 weeks, was lower (p < 0.001) than that of 69 healthy gestation-matched
      healthy infants (3,100, range 2,870-3,381 m/s). Tibial SOS measurements may allow
      radiation-free assessment of metabolic bone disease of prematurity.

PMID- 14707430
TI  - Attenuated lipid peroxidation in preterm infants during subsequent doses of
      intravenous lipids.
AB  - The aim of this study was to determine whether the administration of a lipid
      emulsion containing less polyunsaturated fatty acids but rich in monounsaturated
      fatty acids causes less in vivo lipid peroxidation in preterm infants. The
      prospective intervention study included 13 infants with birth weights and
      gestational ages ranging between 1,100 and 2,660 g and from 28.4 to 32.9 weeks.
      All were in a stable condition and randomly allocated for a 3-hour infusion (0.16
      g/kg/h) of an olive oil-based and a soybean oil + medium chain fatty acid (MCT)
      emulsion on 2 consecutive days. Expired pentane and plasma triglycerides (TGs)
      were measured before, during, and after the 3-hour infusion. Basal exhaled
      pentane averaged 9.4 +/- 7.0 pmol/kg/min (mean +/- SD). During the olive oil
      based emulsion, exhaled pentane increased to 95.2 +/- 56.7, and during soybean
      oil + MCT it increased to 110 +/- 93.9 pmol/kg/min (p < 0.05 both from basal,
      n.s. between preparations). One hour after discontinuation of the infusion,
      exhaled pentane returned to 21.1 +/- 12.6 pmol/kg/min (p < 0.05 vs. basal).
      Combined data on expired pentane measurements demonstrated that on day 1 pentane
      peaked at 124 +/- 87.0 pmol/kg/min which was significantly attenuated to 57.5 +/-
      24.4 pmol/kg/min after an identical dose of lipid on day 2 (p < 0.05). No
      difference in peak TGs was detected between the two preparations or the study
      days. Infusion of a constant dose of intravenous lipids on 2 subsequent days to
      the newborn infants is associated with a reduction in lipid peroxidation. This
      finding may be dependent on normal postnatal maturation or may represent an
      appropriate adaptive response aiming at a reduction in oxidative stress.
      Peroxidation of soybean oil + MCT and olive oil-based lipid emulsions was similar
      in the newborn infants.

PMID- 14707431
TI  - Glutathione recycling and antioxidant enzyme activities in erythrocytes of term
      and preterm newborns at birth.
AB  - We previously demonstrated a high susceptibility of neonatal red blood cells
      (RBC) to oxidative stress at birth. The aim of this study was to compare the RBC
      antioxidant capacity and redox cycle enzyme activities as well as glutathione
      (GSH) recycling in full-term and preterm infants at birth and in normal adults.
      GSH and GSH disulfide (GSSG) concentrations, GSH/GSSG ratio, and the activities
      of glucose-6-phosphate dehydrogenase (G-6-PDH), GSH peroxidase, GSH reductase
      (GR), catalase (CAT), superoxide dismutase (SOD), and hexokinase (HK) were
      measured in RBC of 25 healthy adults and 56 newborns (23 term, 33 preterm) at
      birth. The GSH recycling was measured in adult and newborn RBC exposed to
      oxidative stress (1 mM tert-butylhydroperoxide). The RBC of term and preterm
      babies showed higher GSH, GSSG, G-6-PDH, GR, and HK levels/activities and lower
      GSH/GSSG ratios and higher GSH-recycling rates than those of adults. In preterm
      babies significant correlations were found between G-6-PDH and CAT, GSH, GSH/GSSG
      ratio, and GSSG (r = -0.67, r = 0.71, r = -0.66, p < 0.01; r = 0.71, p < 0.05,
      respectively). In term newborns, statistically significant correlations were
      observed between G-6-PDH and CAT, SOD, and GSH (r = -0.65, r = -0.65, r = -0.69,
      p < 0.01, respectively). The results indicate the central role of the G-6-PDH
      activity in antioxidant defenses. We speculate that preterm babies have prompter
      involvement of antioxidant defenses than term babies.

PMID- 14707432
TI  - The effect of a nebulized NO donor, DPTA/NO, on acute hypoxic pulmonary
      hypertension in newborn piglets.
AB  - NONOates, novel NO donors, are complexes of NO with nucleophiles which
      spontaneously and nonenzymatically release NO in aqueous solution. This study
      sought to determine the cardiopulmonary effects of the nebulized NONOate
      dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced
      pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10
      days old) exposed to hypoxia (Fi(O2) = 0.14) were randomly assigned to receive
      nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia.
      Pulmonary artery (P(pa)) and wedge pressures, systemic (P(sa)) and right atrial
      pressures, cardiac output (CO) and arterial blood gas were measured at baseline
      and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h
      after drug nebulization. Data (means +/- SD) were analyzed by repeated-measures
      analysis of variance. Acute hypoxia resulted in an increase in P(pa) and
      pulmonary vascular resistance (PVR), which was significantly attenuated by
      DPTA/NO nebulization as compared to the PL group (p < 0.0001). Changes in P(sa),
      CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin
      levels were not different between groups. In contrast to the increase in PVR/SVR
      observed during hypoxia in the PL group, there was a significant decrease in this
      ratio after NONOate administration (p < 0.0001). These data show that acute
      hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by
      NONOate nebulization. This response is predominantly in the pulmonary vasculature
      as the PVR/SVR was significantly lower in the treated group. We speculate that
      NONOates may have clinical application in the treatment of persistent pulmonary
      hypertension of the newborn.

PMID- 14707433
TI  - Information processing in very-low-birth-weight children with and without
      attention deficit disorder.
AB  - Very-low-birth-weight children (16 with and 45 without attention
      deficit/hyperactivity disorder) were matched to term-born controls (27 with
      attention deficit/hyperactivity disorder and 30 without) according to age,
      intelligence, and social class of their parents. The children were screened for
      motor, visual, and mental disabilities. The general aim of the study was to
      evaluate information processing stages using the additive factor method of
      Sternberg. The tasks consisted of computerized visual-motor letter recognition
      and arrow detection tasks. The tasks elicited similar prolongations of response
      times, increases in standard deviation of the response times, and increased error
      rates in the four groups. We conclude that very-low-birth-weight and control
      children do not differ in their information processing stages.

PMID- 14707434
TI  - Redox status in very-low birth-weight newborns.
AB  - Inborn metabolic diseases, such as disorders in pyruvate metabolism, in
      gluconeogenesis or in the respiratory chain, may present with lactic acidosis in
      newborn infants. A simple tool to screen for the efficacy of mitochondrial
      oxidation reduction activity is the detection of the redox status through
      simultaneous measurements of plasma lactate, pyruvate and ketone bodies, which
      are strongly influenced by feeding and stress. We present the redox status values
      of 55 very-low birth-weight infants under different nutritional conditions. We
      were able to demonstrate that the redox status values are not dependent on the
      type of nutrition (oral feeding or continuous enteral nutrition). Instead we
      observed a strong difference between newborns with intrauterine growth
      retardation and newborns with appropriate growth. Newborns with intrauterine
      growth retardation show lower preprandial values of glucose and ketone bodies
      than newborns with appropriate weight, but higher levels of lactate and pyruvate;
      nevertheless the lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios
      are normal. The results of the redox status study could suggest the reduced
      activity of gluconeogenesis and, probably, of beta-oxidation in very-low birth
      weight newborns with intrauterine growth retardation.

PMID- 14707435
TI  - Cellular lipid metabolism and the role of lipids in progressive renal disease.
AB  - Dyslipidemia contributes to the rate of progression of atherosclerosis and
      chronic kidney disease. Also, chronic kidney disease leads to the development of
      secondary abnormalities in lipid metabolism that contribute to increased
      cardiovascular morbidity and mortality. This review presents the mechanisms that
      underlie this risk. The mechanisms of normal cellular lipid metabolism and the
      abnormalities that develop in association with inflammation are reviewed. There
      is a special emphasis on foam cells in the kidney and on lipid-mediated changes
      in intrinsic kidney cells that lead to glomerulosclerosis and interstitial
      fibrosis. Correlates to studies performed in whole animals and humans are
      included.

PMID- 14707436
TI  - Effects of eplerenone on heart and kidney in two-kidney, one-clip rats.
AB  - BACKGROUND: The role of aldosterone has been less investigated compared to the
      renin-angiotensin-aldosterone system in renovascular hypertension. The purpose of
      the present study was to compare the effects of a selective aldosterone receptor
      blocker, eplerenone (EP), and an angiotensin II receptor type 1 antagonist
      (AT1RA), losartan (LO) on cardiac and renal damage produced by two-kidney, one
      clip (2K-1C) renovascular hypertension in rats. METHOD: Wistar rats (n = 48) were
      placed on one of six groups. Group 1 received sham operation. From group 2 to 6,
      all rats were made as 2K-1C renovascular hypertension. Group 2 received vehicle.
      Group 3 orally received 100 mg/kg/day of EP from the initiation of the study.
      Group 4 received 100 mg/kg/day of LO, from the initiation of the study. Groups 5
      and 6 received EP and LO from the 4th week after the clipping respectively.
      Systolic blood pressure (SBP) and urinary protein excretion (UPE) were measured
      before and every 2 weeks. The remnant kidney was obtained for histopathological
      analysis and for measurement of endothelial cell nitric oxide synthase (ecNOS)
      gene expression (GE). RESULTS: SBP increased in the placebo group (132.1 +/- 2.4
      vs. 115.0 +/- 0.6 mm Hg in sham group at week 10, p = 0.019). Treatment with LO
      or EP from the beginning of the study decreased SBP significantly as measured in
      the sham group at week 10. The placebo group developed significant UPE (21.7 +/-
      1.9 mg/day) compared with the sham group (13.4 +/- 0.8 mg/day, p < 0.05).
      Treatment with both LO (12.5 +/- 1.5 mg/day, p < 0.01 vs. placebo) and EP (14.8
      +/- 1.0 mg/ day, p < 0.05 vs. placebo) significantly decreased UPE. On the other
      hand, the late start of treatment with EP failed to decrease the increased UPE.
      UPEs were not significantly different between the LO- and EP-treated groups
      throughout the study. There was no significant pathological change in heart and
      kidney in all groups. In heart, ecNOS GE was significantly increased in the EP
      treated (from the beginning of the study) rats compared with placebo group (0.47
      +/- 0.01 vs. 0.43 +/- 0.01, p < 0.05). LO did not have an effect on ecNOS GE in
      heart. In aorta, ecNOS GE was significantly increased in the two EP-treated
      groups compared with the placebo group (0.22 +/- 0.01, 0.22 +/- 0.02 vs. 0.15 +/-
      0.01, p < 0.05, respectively). LO also did not have an effect on ecNOS GE in
      aorta. In kidney, ecNOS GE was significantly increased in the LO group (from the
      beginning of the study) and two EP-treated groups compared with placebo.
      CONCLUSION: This study demonstrated that EP treatment significantly reduced SBP
      and UPE compared with placebo in both development and established 2K-1C
      renovascular hypertension. EP was as effective as LO in lowering the blood
      pressure of this renin-dependent animal model.

PMID- 14707437
TI  - Investigation of conscious recollection, false recognition and delusional
      misidentification in patients with schizophrenia.
AB  - BACKGROUND: Recognition memory (RM) is impaired in patients with schizophrenia,
      as they rely largely on feelings of familiarity rather than conscious
      recollection. It has been suggested that this abnormality may reflect a breakdown
      in strategic memory processes involved in both encoding and retrieval. By
      studying 2 patients with false recognition (FR; patient C.T.) and delusional
      misidentification (DM; patient B.C.), and a group of psychotic control patients,
      we examined proposals that FR and DM exist on a continuum of increasingly severe
      impairment in strategic memory function. METHODS: Executive function,
      autobiographical memory and verbal and facial RM were assessed using standard
      neuropsychological tests and the remember/know paradigm. RESULTS: The psychotic
      control group displayed a significantly reduced reliance on remember judgements
      and compensatory elevation in know judgements on both RM tasks compared with the
      normal control group. Patient B.C. also followed this trend, but in a much more
      pronounced manner. In contrast, patient C.T. displayed a qualitatively different
      performance profile, which was marked by an increased dependence on remember
      responses. CONCLUSIONS: We have presented evidence which support proposals that a
      breakdown in strategic memory and executive dysfunction are more pronounced in DM
      than FR. However, the small sample size precludes any firm conclusions being
      drawn.

PMID- 14707438
TI  - Inter-rater reliability of the Brazilian version of the Paykel scale of stressful
      life events.
AB  - The inter-rater reliability of the Brazilian version of the Recent Life Events
      Interview, developed by Paykel in order to evaluate stressful life events, was
      studied in 21 psychiatric inpatients and 20 psychiatric outpatients. Data
      concerning the agreement between the two raters showed a satisfactory reliability
      for specific occurrence of events, month of occurrence, independence of events
      and negative objective impact. This preliminary study suggests that the Brazilian
      version of the Recent Life Events Interview is a reliable instrument for the
      assessment of life events in Brazilian samples.

PMID- 14707439
TI  - Sleep disturbances in somatoform pain disorder.
AB  - Patients with chronic somatoform pain often complain about sleep disorders.
      However, sleep disorder/disturbances are not an integrated part of the somatoform
      disorders in the DSM-IV and the ICD-10. Sleep is important for recreation.
      Deprivation of deep sleep stages is experimentally linked to muscle pain.
      Therefore, sleep disorder may play an important part in the persistence of
      somatoform pain disorder. The aim of the study was to evaluate the frequency of
      sleep disorder in patients with somatoform pain disorder and to correlate it with
      comorbid depression, pain parameters and psychosocial parameters. METHOD: In this
      study, 147 patients (mean age: 48.8 years; SD: 11.0) with the diagnosis of a
      somatoform pain disorder were studied with regard to affective comorbidity, pain
      duration (months), maximum pain within the last month, minimum pain within the
      last month and medium pain within the last month, psychosocial disability within
      the last month and the presence of a sleep disorder. RESULTS: Eighty-four percent
      of the patients had a sleep disorder. The patients with a sleep disorder had
      significantly higher maximum and medium pain, a significantly higher level of
      psychosocial disability and a significantly lower overall subjective well-being.
      The medium pain and psychosocial disability in leisure and social activities are
      significant predictors for sleep disorder. CONCLUSIONS: The presence of a sleep
      disorder may be a hint for higher pain intensity and a higher level of
      psychosocial disability. Sleep disorder may be a factor in the persistence and
      aggravation of pain as well as psychosocial disability. Therefore, sleep disorder
      should be integrated in the therapeutic targets. It is suggested that sleep
      disorder should be a diagnostic criterion in somatoform pain disorder.

PMID- 14707440
TI  - Evolution of endotoxin-induced lung injury in the rat beyond the acute phase.
AB  - OBJECTIVES: Intratracheal endotoxin in rats causes acute lung injury. Here we
      have addressed the cellular physiopathology of lung recovery from that injury.
      METHODS: The lungs of 5 untreated rats and rats treated with intratracheal
      endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by
      light and electron microscopy and immunohistochemistry. RESULTS: In the acute
      phase there was a reduction in the aerated spaces (p < 0.01); diffuse
      infiltration of granulocytes and macrophages; hyperplasia of type-II pneumocytes,
      and hypertrophy of interstitial cells. Aerated spaces improved during recovery.
      In the early recovery phase (3-8 days) the compartmentalization of infiltrating
      cells varied significantly (p < 0.01): macrophages remained widespread while
      neutrophils were inside blood vessels. Many pneumocytes were intermediate between
      type-I and type-II cells. In the late recovery phase (15 days) the infiltrate
      disappeared; myofibroblasts were significantly more than previously (p < 0.01)
      and extracellular matrix was abundant; type-II pneumocytes contained non
      lamellated lipid inclusions. CONCLUSIONS: Macrophages play a pivotal role in the
      damage-repair processes of the lung following endotoxin injury, leading to an
      increase in extracellular matrix, differentiation of myofibroblasts and altered
      secretion of surfactant by newly differentiated type-II pneumocytes.

PMID- 14707441
TI  - Increased urinary concentration of collagen type II C-telopeptide fragments in
      patients with osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is characterized by a progressive degeneration of
      articular cartilage and loss of joint function. We hypothesized that degradation
      of articular cartilage results in increased fragmentation of collagen type II.
      Thus, the concentrations of degradation products of this major cartilage matrix
      protein may increase in body fluids of patients with OA. METHODS: Monoclonal
      antibodies specific for a human collagen type II C-telopeptide (CTx-II) fragment
      were used in an ELISA for quantification of collagen type II fragments in urine.
      Clinical assessment of 88 patients with advanced OA of either hip or knee and 48
      age-matched controls was performed with the Harris hip score, the Merle d'Aubigne
      score and a knee score. Joint space narrowing and the Kellgren and Lawrence score
      were assessed as radiological signs of OA. RESULTS: The concentration of CTx-II
      was significantly higher in OA patients compared with controls (527 vs. 190
      ng/mmol, p < 0.001) whether the patients were diagnosed with hip OA (n = 51) or
      knee OA (n = 37). Mean CTx-II levels were higher in hip OA than in knee OA and a
      slight increase in levels with age was observed in the controls, but not in OA
      subjects. CONCLUSION: Elevation of CTx-II in urine of patients with severe OA
      compared with a control group suggests that collagen type II derived fragments
      may serve as markers for OA.

PMID- 14707442
TI  - Digital chemospectrophotographic identification of intracellular hyperlipidemia
      in diabetic endometrial epithelial cells: structural and metabolic basis of
      organoatrophy.
AB  - OBJECTIVE: Digital chemospectrophotographic (DCSP) microscopic analysis and
      evaluation methodology applicable for enhanced cytopathological analysis of
      diabetes-induced, cytohyperlipidemia-associated cellular involution in
      endometrial epithelial and stromal tissues that promotes reproductive dysfunction
      and organoatrophy. METHODS: Combined light microscopy (LM), transmission electron
      microscopy (TEM) and described DCSP evaluation of endometrial samples collected
      from control (+/?) and genetically diabetic (db/db) C57BL/KsJ, hyperglycemic
      hyperinsulinemic (type II) mice, designed to enhance the intracellular
      localization of chemically specified triglyceride and free fatty acid
      depositions, on progressive reproductive tract atrophy and cellular involution
      indices. RESULTS: Compared to both the LM and TEM analysis of cytopathological
      changes associated with diabetes-induced endometrial involution and reproductive
      dysfunction, the application of DCSP provided enhanced pathovisual analysis of
      chemical-specific metabolic alterations and cytoplasmic structural changes which
      accompany cytohyperlipidemia-induced endometrial epithelial cell apoptosis and
      reproductive tract atrophy. CONCLUSIONS: DCSP analysis provides an enhanced
      analytical method for the evaluation of cytoplasmic changes associated with the
      expression of genomic-, endocrine- or metabolic-based disease states by providing
      intercytoplasmic specific chemical or metabolic substrate alterations to be
      identified from conventional pathocellular preparations without requiring the use
      of exogenous ligand binding or fluorescent methodologies, allowing for a more
      complete metabolic and cellular evaluation of cytoplasmic indices associated with
      organoatrophy.

PMID- 14707443
TI  - Expression of cyclooxygenase-1 and cyclooxygenase-2 in human esophageal mucosa,
      dysplasia and carcinoma.
AB  - OBJECTIVE: COX (cyclooxygenase), a prostaglandin H synthase, catalyzes the rate
      limiting step in prostaglandin biosynthesis. Two isoforms of COX have been
      identified: COX-1 and COX-2. We examined the expression of COX-1 and COX-2 in
      esophageal normal mucosa, dysplasia and squamous cell carcinoma (SCC). METHODS:
      The expression of COX-1 and COX-2 in 80 surgically removed esophagi due to SCC,
      as well as in 5 human esophageal SCC cell lines was analyzed, using
      immunohistochemistry and Western blot analyses. RESULTS: COX-1 and COX-2 were
      variably expressed in the SCC cell lines. Higher COX-1 expression was noted in 31
      (41.9%) of the 74 specimens of normal mucosa, in none of the 40 specimens of
      dysplastic mucosa and in 15 (18.8%) of the 80 specimens of SCC, the frequency
      being significantly higher in normal mucosa than in dysplasia or SCC (p < 0.0001,
      p = 0.0018, respectively). COX-1 expression was significantly higher in well
      differentiated SCC than in moderately or poorly differentiated SCC (p < 0.01).
      Higher COX-2 expression was noted in none (0.0%) of the specimens of normal
      mucosa, in 12 (30%) of the specimens of dysplastic mucosa, and in 41 (51.3%) of
      the speciments of SCC, the frequency being significantly higher in SCC than in
      normal mucosa or dysplasia (p < 0.0001, p = 0.0278, respectively). CONCLUSIONS:
      COX-1 is expressed in normal esophageal mucosa and is occasionally induced in
      well-differentiated SCC, whereas COX-2 expression is more characteristic of
      dysplasia and carcinoma than of normal mucosa, implying a possible association
      with cell differentiation in the former, and esophageal tumorigenesis in the
      latter.

PMID- 14707444
TI  - Engraftment of adult human lung tissue in nonobese diabetic/severe combined
      immunodeficient mice: a novel lung epithelial regeneration model.
AB  - OBJECTIVES: Injury causes the disruption of homeostatic cell-cell interactions
      and epithelial regeneration is part of the threshold response. Due to the lack of
      a good animal model for the investigation of these mechanisms, the kinetics of
      cell proliferation after injury to the human respiratory tract are poorly
      understood. METHODS: To create a better model of human bronchioloalveolar
      epithelial regeneration, we engrafted adult human lung tissue into nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice. Then the lung tissue
      was studied at various times up to 20 weeks after implantation. RESULTS: The
      xenografts of bronchiolar epithelium showed characteristic features, including
      positivity for specific human antigens, and extensive regeneration was observed
      within 8 weeks after implantation. In addition, a few alveolar type II epithelial
      cells expressing prosurfactant protein C were detected in some areas. The distal
      alveolar spaces were filled with protein-rich material and were markedly dilated.
      Abundantly ciliated secretory epithelium, which was similar to normal adult
      bronchiolar epithelium, was observed within 16 weeks after implantation in the
      mice. All of the human lung tissue specimens that were implanted subcutaneously
      into the backs of the mice developed well and remained viable for 20 weeks. Each
      type of adult human lung epithelial cell showed a different mode of
      proliferation. Bronchiolar epithelial cells proliferated earlier, with MIB-1
      labeling of up to 20% of the cells in the grafts at 8 weeks, while alveolar type
      II cells proliferated later, with labeling of up to 5% of graft cells at 12
      weeks. CONCLUSION: This model seems to allow adult human lung epithelial
      regeneration to be investigated in vivo over the long term.

PMID- 14707445
TI  - Infrequent alteration in the p53R2 gene in human transitional cell carcinoma of
      the urinary tract.
AB  - OBJECTIVE: Functional defects in DNA repair have been shown to be associated with
      genomic instability followed by cancer. Recently, p53R2 [p53-inducible
      ribonucleotide reductase (RR) small subunit 2 homologous] was identified as a
      novel RR gene which is directly regulated by p53 protein in the G1 and G2 phases
      of the cell cycle supplying nucleotides to repair damaged DNA. METHODS: We
      performed genetic analyses of p53R2 to determine whether p53R2 alterations play
      significant roles in urothelial tumorigenesis. Genomic DNA from 108 primary
      transitional cell carcinomas (TCCs; 81 of the urinary bladder and 27 of the renal
      pelvis or ureter) was analyzed for mutation in the p53R2 gene by direct
      sequencing. We focused on three domains of the p53R2 gene: one RR small subunit
      signature involving codons 120-146 (region 1) and two putative nuclear
      localization signal sequences, involving codons 149-155 (region 2) and codons 163
      169 (region 3). In addition, a p53-binding site of 20 nucleotides in intron 1 of
      p53R2 was also analyzed. RESULTS: One renal pelvic TCC (0.9%: 1/108) had a single
      base substitution in p53R2 with a G to T transversion resulting in the amino acid
      substitution Glu136 --> Asp. This base substitution was localized within the
      domain of exon 4 encoding the RR small subunit signature, and causes an amino
      acid substitution in one of the most highly conserved regions of p53R2, in which
      human R2 and yeast RNR2 and RNR4 proteins are highly homologous. CONCLUSION: This
      finding provides the in vivo evidence for the infrequent involvement of
      alterations in p53R2 inhuman urothelial TCCs.

PMID- 14707447
TI  - Multiple signal pathways are involved in the mitogenic effect of 5(S)-HETE in
      human pancreatic cancer.
AB  - Pancreatic carcinoma is characterized by poor prognosis and lack of response to
      conventional therapy. The reasons for this are not fully understood. We have
      reported that inhibition of 5-lipoxygenase abolished proliferation and induced
      apoptosis in pancreatic cancer cells while the 5-lipoxygenase metabolite, 5(S)
      hydroxyeicosatetraenoic acid [5(S)-HETE] stimulated pancreatic cancer cell
      proliferation. The current study was designed to investigate the underlying
      mechanisms for 5(S)-HETE-stimulated proliferation of pancreatic cells. Two human
      pancreatic cancer cell lines, PANC-1 and HPAF, were used. Cell proliferation was
      monitored by thymidine incorporation and cell counting. Phosphorylation of
      P42/44(MAPK) (mitogen activated protein kinase, ERK), MEK (MAPK/ERK kinase), P38
      kinase, JNK/SAPK (c-Jun N-terminal kinase/ stress-activated protein kinase), AKT
      and tyrosine residues of intracellular proteins was measured by Western blot
      using their corresponding phospho-specific antibodies. The results showed that
      (1) 5(S)-HETE markedly stimulated pancreatic cancer cell proliferation in a time-
      and concentration-dependent manner; (2) 5(S)-HETE induced tyrosine
      phosphorylation of multiple intracellular proteins while the tyrosine kinase
      inhibitor, genestein, blocked 5(S)-HETE-stimulated cell proliferation; (3) 5(S)
      HETE significantly stimulated both MEK and P42/44(MAPK) phosphorylation and the
      MEK inhibitors, PD098059 and U0126, inhibited 5(S)-HETE-stimulated proliferation
      in these two cell lines; (4) 5(S)-HETE also stimulated P38 kinase phosphorylation
      but the P38 inhibitor, SB203580, did not effect 5(S)-HETE-stimulated cell
      proliferation; (5) 5(S)-HETE markedly stimulated AKT phosphorylation while the
      phosphatidylinositide-3 (PI3)-kinase inhibitor, wortmannin, blocked 5(S)-HETE
      stimulated cell proliferation; (6) phosphorylation of JNK/SAPK was not induced by
      5(S)-HETE, and (7) the general protein kinase C (PKC) inhibitor, GF109203X, did
      not affect 5(S)-HETE-stimulated cancer cell proliferation. These findings suggest
      that intracellular tyrosine kinases, MEK/ERK and PI3 kinase/AKT pathways are
      involved in 5(S)-HETE-stimulated pancreatic cancer cell proliferation but P38
      kinase, JNK/SAPK and PKC are not involved in this mitogenic effect.

PMID- 14707448
TI  - Usefulness of 99mTc-tetrofosmin scintigraphy in different variants of Kaposi's
      sarcoma.
AB  - We investigated (99m)Tc-tetrofosmin scintigraphy in 27 patients with Kaposi's
      sarcoma: 20 had classic (CK), 5 AIDS-associated (AK) and 2 transplantation
      associated (TK) variants. Twenty-three patients had clinically evident cutaneous
      and/or mucosal lesions, 9 of them with associated sarcomatous lymphadenopathy; 2
      TK patients had only lymph nodes or other extracutaneous Kaposi sites. Both
      planar and SPECT (99m)Tc-tetrofosmin scintigraphies were performed in all cases
      and neck pinhole (P)-SPECT in selected patients. (99m)Tc-tetrofosmin uptake was
      observed in 88% of patients with clinically evident cutaneous and/or
      extracutaneous Kaposi lesions. Scintigraphy gave additional information on
      cutaneous lesion extent, particularly SPECT regarding deep invasion and
      subclinical sites in some cases. However, scintigraphy was less sensitive in the
      detection of small, isolated and scattered lesions. SPECT/P-SPECT were positive
      in 8/8 patients with sarcomatous lymph nodes, planar imaging in 5/8,
      ultrasonography in 7/8, while all procedures were negative in 6 other patients
      with reactive or HIV infection lymph nodes. SPECT demonstrated lymphadenopathy
      remission in 1 TK patient after immunosuppressive therapy modification and, like
      planar imaging, ascertained an associated lymphoma with (67)Ga-citrate combined.
      (99m)Tc-tetrofosmin scintigraphy, especially SPECT, can be useful both in the
      detection and staging of Kaposi sarcoma lesions as a complementary tool to
      clinical and other conventional diagnostic methods.

PMID- 14707450
TI  - Role of mammography, ultrasound and large core biopsy in the diagnostic
      evaluation of papillary breast lesions.
AB  - BACKGROUND: It is well recognized that distinguishing benign from malignant
      papillary lesions of the breast may pose challenging diagnostic problems. To
      prospectively evaluate the potential role of mammography, ultrasound and image
      guided core biopsy in the diagnosis of papillary lesions of the breast. METHODS:
      1,442 women consecutively underwent 14-gauge core biopsy and in 51 cases (3.5%) a
      diagnosis of papillary lesion was formulated. Both radiologists and pathologists
      independently expressed their degree of suspicion of malignancy (not suspicious,
      low, moderate, high) on the basis of radiological and core biopsy findings,
      respectively. Surgical excision of the lesion was used as gold standard and
      diagnostic agreement was assessed by the kappa statistic. RESULTS: At surgery, 19
      of the 49 (38.7%) resected cases had a diagnosis of malignancy. A poor agreement
      was found between mammography and core biopsy results in the categorization of
      suspicion of malignancy (k = 0.03). Similar data were obtained between ultrasound
      and core biopsy (k = 0.07). A poor agreement was also observed between
      radiological and surgical results (k < 0.20). In contrast, a good agreement was
      found between core biopsy and surgical samples (k > 0.70). However, 5 (26%) out
      of the 19 malignant cases at surgery were judged as benign or probably benign on
      core biopsy. Depending on how the categories of suspicion on core biopsy were set
      up, the range of sensitivity was 74-89%, whereas specificity ranged from 91 to
      97%. CONCLUSIONS: Image-guided large core biopsy allows for a correct diagnosis
      in the majority of papillary lesions. However, its sensitivity is not good enough
      for surgical excision to be avoided.

PMID- 14707449
TI  - Rituximab for treatment of advanced extranodal marginal zone B cell lymphoma of
      the mucosa-associated lymphoid tissue lymphoma.
AB  - BACKGROUND: Extranodal marginal zone B cell lymphoma of the mucosa-associated
      lymphoid tissue (MALT) is a relatively common type of lymphoma. Owing to its B
      cell lineage, it appears to be a potential target for treatment with the CD20
      antibody rituximab. We present an analysis of our experience with rituximab for
      treatment of patients with advanced MALT lymphoma. PATIENTS AND METHODS: A
      retrospective analysis of patients with histologically verified MALT lymphoma
      undergoing treatment with rituximab was done. After reassessment of histological
      samples for the presence of MALT lymphoma, patients were evaluated as regards
      date of diagnosis, prior therapy for MALT lymphoma, sites of involvement upon
      treatment with rituximab, clinical response in terms of complete remission (CR),
      partial response (PR), stable disease (SD) and progressive disease as well as
      symptomatic response, duration of response and survival. RESULTS: A total of 9
      patients with advanced MALT lymphoma undergoing therapy with single-agent
      rituximab were identified. All patients received treatment at a dose of 375
      mg/m(2) once weekly x4. One patient each had relapsed after chemotherapy and
      radiation, respectively, while none of the other 7 patients had received prior
      cytotoxic treatment or radiation. Three patients achieved a CR, 2 patients had PR
      for 6 and 14 months, while the remaining patients had SD between 8 and 18+
      months. One patient died of progressive disease in spite of the initiation of
      chemotherapy and 1 patient succumbed to a cardiovascular event while having been
      in ongoing PR for 11 months. The other 7 patients are currently alive with
      disease 10-27 months after initiation of therapy. Follow-up biopsies for
      histological assessment were available in 5 patients with gastric lymphoma. In 1
      patient with SD, however, persistence of CD20-positive cells within
      lymphoepithelial lesions was noted in spite of almost complete depletion of B
      lymphocytes from the normal gastric mucosa, suggesting either recirculation of
      MALT lymphoma cells to these lesions or defining lymphoepithelial lesions as a
      sanctuary site from rituximab penetration. CONCLUSION: Rituximab had only
      moderate activity in terms of inducing objective responses in our unselected and
      heterogeneous cohort of patients with disseminated MALT lymphoma. Long-term
      disease stabilization, however, along with a symptomatic benefit was seen in all
      patients. Our data nevertheless indicate that rituximab might not optimally
      penetrate into the gastric mucosa in all patients.

PMID- 14707451
TI  - Impact of interval debulking surgery on clinical outcome in primary unresectable
      FIGO stage IIIc ovarian cancer patients.
AB  - OBJECTIVES: To report the results of neoadjuvant chemotherapy (NACT) and the
      impact of interval debulking surgery (IDS) on clinical outcomes of patients
      considered unresectable at primary surgery. METHODS: Retrospective analysis was
      carried out on 73 consecutive stage IIIc ovarian cancer patients treated with
      platinum-based NACT followed by IDS. Their clinical outcomes were compared with
      those of 111 consecutive stage IIIc ovarian cancer patients treated with primary
      cytoreduction followed by platinum-based adjuvant chemotherapy. RESULTS: Patients
      who underwent successful IDS had a more favorable prognosis than those who did
      not in terms of time to progression (TTP) (p = 0.00001), and overall survival
      (OS) (p = 0.0001). On the other hand, in the group of patients that underwent
      successful IDS, no differences in survival outcomes were observed between
      patients with no residual disease and patients with macroscopic residual disease
      <2 cm after IDS (p = n.s.). CONCLUSIONS: NACT followed by successful IDS can
      achieve good results in terms of survival outcomes in a high percentage of
      chemoresponsive IIIc ovarian cancer patients classified as unresectable at
      primary surgery. These results are in fact inferior to those achievable with
      optimal primary cytoreduction; however, they were quite similar to those seen
      with suboptimal primary cytoreduction.

PMID- 14707452
TI  - Metal contents in the liver of patients with chronic liver disease caused by
      hepatitis C virus. Reference to hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the relationship
      between trace metals and the prevalence of hepatocellular carcinoma (HCC) in
      patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis C virus
      (HCV). METHODS: We measured the contents of copper, iron, and zinc in HCC tissue
      (n = 112), dysplastic nodules (n = 7), and liver parenchyma in patients with (n =
      112) and without (n = 12; 7 with grade F3 fibrosis, 5 with grade F4 fibrosis)
      HCC. Metals were quantified in thin-needle biopsy specimens using the particle
      induced X-ray emission method (PIXE). RESULTS: Copper level in liver parenchyma
      was higher in patients with HCC than in those without HCC (p < 0.01), while there
      was no such difference in hepatic iron. In patients with grade F4 fibrosis,
      copper content in the liver parenchyma was higher in the presence of HCC than in
      its absence (p < 0.05). Multiple regression analysis showed that the only factor
      significantly associated with the coexistence of HCC in HCV-positive patients
      with chronic liver disease was the copper level in the liver parenchyma.
      CONCLUSIONS: Hepatic copper overload may contribute to the development of HCC in
      HCV-positive patients with chronic hepatitis or cirrhosis.

PMID- 14707446
TI  - Vascular gene expression in atherosclerotic plaque-prone regions analyzed by
      representational difference analysis.
AB  - OBJECTIVES: Atherosclerotic plaques are known to develop and progress where the
      endothelium is subjected to turbulent blood flow. We have applied cDNA
      representational difference analysis (RDA) to study vascular gene expression in
      mouse aorta in a model for atherosclerosis. METHODS: Gene expression profiles
      were investigated in plaque-prone and plaque-resistant localizations in the
      ascending aorta and arch in 8-week-old ApoE-/- and LDLR-/- mice. Total RNA was
      extracted and two rounds of subtraction were performed; the difference products
      were characterized in detail by shotgun cloning and analysis of more than 2,700
      gene sequences. RESULTS: The identified differentially expressed gene sequences
      include both genes with known involvement in vascular gene expression and genes
      previously not implicated in vascular processes. For example, CD36 and caveolin,
      previously reported for their participation in the progression of
      atherosclerosis, were found to have an increased expression in vessel
      localizations thought to be especially susceptible to plaque formation.
      CONCLUSIONS: This report provides new in vivo information of expressed genes that
      can be useful for further investigations of the molecular mechanisms in focal
      localization of atherosclerosis.

PMID- 14707453
TI  - Changes in apoptosis and mitotic index, p53 and Ki67 expression in various types
      of oral leukoplakia.
AB  - INTRODUCTION: Leukoplakia is the most frequent pre-blastomatous alteration in the
      oral cavity. Its potential for malignant transformation is unpredictable. The aim
      of the present study was to provide data about the processes and molecular
      genetic background of this disease. MATERIALS AND METHODS: Leukoplakias of 15
      patients and oral squamous cell carcinomas of 3 patients treated at the
      Department of Periodontology and Oral Surgery, Semmelweis University, were
      studied by histological and immunohistochemical methods. The samples were fixed
      in 4% formalin and embedded in paraffin. Hematoxylin and eosin staining, TUNEL
      reaction (Apop-Detect kit), and immunohistochemical reactions for Ki67 and p53
      were applied. The severity of dysplasia, the mitotic and apoptotic indices and
      expression as well as distribution of Ki67 and p53 were examined and compared to
      the clinical appearance of leukoplakia. RESULTS: The mitotic and apoptotic
      indices and Ki67 expression increased significantly in parallel with the severity
      of dysplasia and also with the clinical stage (homogenous, nodular,
      erythroleukoplakia). The positivity and intracellular localization of (mutant)
      p53 varied according to the clinical form of leukoplakia. Homogenous and nodular
      forms showed cytoplasmic staining, while erythroleukoplakia and carcinoma cases
      were characterized by nuclear positivity. CONCLUSIONS: The increased apoptotic
      and Ki67 indices may indicate an unfavorable prognosis for leukoplakia. The
      expression of Ki67 and p53 in various forms of leukoplakia point to the
      increasing instability of the genome in parallel with the severity of
      leukoplakia.

PMID- 14707454
TI  - Low collagenase-1 (MMP-1) and MT1-MMP expression levels are favourable survival
      markers in advanced colorectal carcinoma.
AB  - OBJECTIVE: Extracellular matrix degradation is required for invasive growth and
      metastasis formation in colorectal carcinoma; therefore, we examined matrix
      metalloproteinases expression (MMP-1, MMP-13 and MT1-MMP) and apoptosis in
      tumours from 49 patients with advanced colorectal disease. METHODS: MMP
      expression was determined immunohistochemically and apoptotic index (AI) was
      ascertained using the TUNEL assay. RESULTS: Low levels of MT1-MMP, MMP-1 and AI
      were found to be favourable markers significantly associated with longer
      survival. MT1-MMP expression levels below the median (</=14.0% of tumour cells)
      were associated with better overall survival (median 26.2 vs. 15.6 months, p =
      0.02) and MMP-1 expression levels below the median (</=28.7% of tumour cells)
      correlated with longer survival following metastasis (median 21.5 vs. 13.3
      months, p = 0.05). MT1-MMP, MMP-1 and AI were all found to have significant
      independent effects on survival. Interestingly, MMP-1 expression levels above the
      median were associated with distal disease of the colon (p = 0.02). CONCLUSIONS:
      These findings reveal that MT1-MMP and MMP-1 expression levels and AI are useful
      prognostic indicators in advanced colorectal carcinoma and suggest that markers
      of MMP expression might be used in identifying patients who would benefit from
      new treatment modalities involving MMP inhibitors.

PMID- 14707455
TI  - The supplementary diagnostic power of selected immunohistochemical, molecular
      genetic and infective parameters in epithelial hyperplastic laryngeal lesions.
AB  - OBJECTIVES: MIB-1 and p53 protein expression, loss of heterozygosity (LOH),
      microsatellite instability (MSI) of di- and mononucleotide repeats, and HPV
      status were tested for their potential to characterize different stages of
      epithelial hyperplastic laryngeal lesions (EHLL). METHODS: Thirty-two EHLL were
      reclassified according to the Ljubljana classification into simple (SH), abnormal
      (AbH), atypical hyperplasia (AtH) and carcinoma in situ, and investigated by
      immunohistochemical methods, PCR and direct sequencing analysis. RESULTS: MIB-1
      increased with progressive grades of EHLL, whereas p53 protein expression was
      distinctive only between SH and AbH. LOH showed increasing frequency with grades
      of the lesions, but the distribution of altered loci (9p, 9q, 10q, 11q, 17p) was
      not qualified to differentiate between the stages. MSI was detected in SH, AbH
      and AtH without clear correlation to histopathological grading. HPV infection
      occurred mostly in SH and AbH (both: 66.7%). CONCLUSION: MIB-1 labeling and
      allelic loss could assist histopathological diagnosis in the entire spectrum of
      EHLL, whereas the MSI results point to a genetic instability of the laryngeal
      mucosa in general and are therefore not helpful in the distinction of different
      stages of EHLL. However, future molecular genetic analyses should consider more
      late events of laryngeal carcinogenesis to improve their diagnostic potential.
      Furthermore, our results indicate that nonrisky and risky EHLL could probably be
      caused by different exogenous factors.

PMID- 14707456
TI  - Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and
      poor prognosis in oral squamous cell carcinomas.
AB  - Previous studies have shown that low levels of p27(KIP1), an inhibitor of G1
      cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor
      prognosis in a variety of cancers. Decreased levels of p27(KIP1) are caused, at
      least in part, by an acceleration of degradation with Skp2 (S-phase kinase
      associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This
      investigation was undertaken to examine whether the Skp2 and Jab1 expression is
      correlated with p27(KIP1) protein levels, and how it is clinically relevant in
      oral squamous cell carcinoma (OSCC). The correlations between p27(KIP1) and Skp2,
      and p27(KIP1) and Jab1 expression were evaluated by Western blot analysis.
      Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant
      inverse correlation was found between levels of p27(KIP1) and Skp2, and p27(KIP1)
      and Jab1 (p < 0.0001). Thus, decreased levels of p27(KIP1) were associated with
      strongly increased levels of Skp2 and Jab1, whereas high levels of p27(KIP1)
      coincided with low levels of Skp2 and Jab1. Reductions of p27(KIP1) expression
      and overexpression of Skp2 and Jab1 were significantly associated with cervical
      lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is
      associated with the reduction of p27(KIP1) expression, and may have a role in the
      progression of OSCC.

PMID- 14707457
TI  - Seprase, a membrane-type serine protease, has different expression patterns in
      intestinal- and diffuse-type gastric cancer.
AB  - OBJECTIVE: Seprase is an integral membrane serine proteinase with gelatinase
      activity that may be involved in cancer invasion and metastasis. However, the
      pathophysiologic significance of its expression in gastric cancer tissue has not
      been fully elucidated. METHODS: Seprase expression and distribution in gastric
      cancer specimens obtained from 133 patients were examined by immunohistochemistry
      and immunoblotting. RESULTS: Immunohistochemistry showed that in intestinal-type
      cancer, which includes well and moderately differentiated adenocarcinoma, seprase
      immunoreactivity was mainly recognized in the moderately differentiated cells and
      not in the well differentiated cells. In the diffuse type, which includes poorly
      differentiated adenocarcinoma and signet ring cell carcinoma, seprase
      immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The
      reactive pattern in the cells was different between moderately differentiated
      adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell
      membrane also apparently reacted in the former, while only the cytoplasm reacted
      diffusely in the latter. Seprase immunoreactivity was also recognized in
      endothelial cells and stromal cells especially adjacent to tumor nests. The
      immunoreactivity of the stromal cells was more abundant in the intestinal type
      than in the diffuse type, and these stromal expressions of seprase in the
      intestinal type correlated with the liver (13/13 = 100% of cases with metastases)
      or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting
      showed that the levels of seprase protein were higher in intestinal-type cancer
      than in diffuse-type cancer. CONCLUSION: These results suggested that there is a
      difference in seprase expression between intestinal- and diffuse-type gastric
      cancer; this difference may reflect distinct biological features of these types
      of cancer.

PMID- 14707458
TI  - Loss of p27 expression is associated with poor prognosis in stage I-II pancreatic
      cancer.
AB  - OBJECTIVE: p27 is a cyclin-dependent kinase inhibitor that prevents progression
      of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with
      poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27
      expression has been correlated with high tumor grade and advanced clinical stage,
      but data on its prognostic value are lacking. METHOD: In this retrospective
      study, the association between immunohistochemical p27 expression and prognosis
      was evaluated in 147 patients with pancreatic cancer using a commercial anti
      Kip1/p27 monoclonal antibody. RESULT: p27 expression was generally low; in 103 of
      the 147 pancreatic cancer tumors examined, no nuclear staining was observed and
      in only 5 specimens did more than 50% of the nuclei stain, probably reflecting
      the aggressive nature of the disease. Loss of p27 expression was associated with
      poor prognosis in stage I-II pancreatic adenocarcinoma; the 5-year survival for
      p27 negative patients was 3.6% compared with 20% for p27-positive patients (p =
      0.03). In a multivariate survival analysis in patients with stage I-II disease,
      p27 (HR 1.8) was a significant prognostic factor, independent of grade (RR 2.9).
      There was no association between p27 and other clinical variables. In conclusion,
      tissue expression of p27 is a significant predictor of 5-year survival in stage I
      II pancreatic adenocarcinoma.

PMID- 14707459
TI  - Taxol plus gemcitabine and vinorelbine given every other week in advanced chemo
      naive non-small cell lung cancer patients.

PMID- 14707460
TI  - Visualizing T cell migration in vivo.
AB  - Ever since the realization that T lymphocytes are key players in the defense
      against pathogens and tumors, a major aim of immunologists has been to understand
      the relationship between the functional and migratory properties of antigen
      specific T cells. The current paradigm proposes that T cells follow organ
      specific trafficking pathways to exit from blood into the extravascular
      compartment. T cell homing is regulated at the level of adhesion molecules and
      chemokine receptors, whose expression is linked tightly to the differentiation
      state of the cell. Naive T lymphocytes follow relatively uniform recirculation
      routes through secondary lymphoid organs, the molecular cues of which are fairly
      well understood. As effector and memory T cells must be capable of reaching
      virtually any site in the body, their migratory behavior is considerably more
      heterogeneous. During the past few years, innovative approaches for tracking T
      cells in vivo have emerged. Here, we review recent technical developments in
      experimental methods for the visualization of T cells both at the population and
      single cell level in vivo, and discuss what these methods have taught us about T
      cell trafficking.

PMID- 14707461
TI  - Immunotherapy of malignant diseases. Challenges and strategies.
AB  - In recent years, there has been growing interest in the application of
      immunotherapy as an alternative to chemotherapy and radiotherapy for the
      treatment of malignant diseases. This interest is due to a variety of factors,
      including revival of the immunosurveillance theory, availability of well-defined
      and structurally characterized human tumor-associated antigens (TAAs), progress
      in our understanding of the molecular pathways required for induction and
      maintenance of an immune response, and advances in methodologies to generate TAA
      specific cytotoxic T lymphocytes (CTLs) and monoclonal antibodies (mAbs) as
      immunological probes. However, contrary to the positive results obtained with TAA
      specific immunotherapy in animal model systems, the clinical response in patients
      has been disappointing. Frequently, the immune responses do not correlate with
      the clinical responses. Analysis of the underlying mechanisms of this dichotomy
      have identified the low immunogenicity of TAAs, the lack of immunological markers
      to predict clinical outcomes, and the ability of tumors to escape immune
      recognition and destruction as challenges to the development and application of
      immunotherapy. In this paper, we have reviewed the mechanisms underlying immune
      unresponsiveness to TAAs and strategies to overcome this unresponsiveness in the
      humoral and cellular immune responses, highlighting findings from different
      antigenic systems to prove the validity of these strategies. Additionally, we
      have addressed limitations to TAA-targeting immunotherapy as a result of the
      genetic instability of tumor cells, and have discussed strategies to overcome
      this limitation by targeting immunotherapy to molecules implicated in tumor
      associated angiogenesis. Lastly, we have concluded by indicating the need to
      refine the implementation of clinical trials of immunotherapy, and to emphasize
      combination therapies to counteract the multiple tumor escape mechanisms.

PMID- 14707462
TI  - Immunomodulation by polyunsaturated fatty acids: mechanisms and effects.
AB  - Polyunsaturated fatty acids (PUFAs) modulate immune responses, thereby exerting
      beneficial effects in a variety of inflammatory disorders. PUFAs of the n-3
      series that are found in marine fish oils are particularly effective. A variety
      of molecular mechanisms have been found to explain how PUFAs could interfere with
      immune cell function. PUFAs alter eicosanoid (prostaglandin, leukotriene)
      synthesis, orphan nuclear receptor activation (e.g. peroxisome proliferator
      activated receptors, liver X receptors) and T lymphocyte signaling by changing
      the molecular composition of special signaling platforms called lipid rafts. This
      review discusses these mechanisms in detail with respect to their probable
      relevance in vivo. In addition, the effects of PUFAs on the immune system in
      general are summarized, as are clinical effects in rheumatoid arthritis,
      inflammatory bowel disease and sepsis.

PMID- 14707463
TI  - Development and use of an ELISA test to detect IgE antibody to Cry9c following
      possible exposure to bioengineered corn.
AB  - BACKGROUND: Starlink(TM), a variety of corn genetically engineered to contain the
      insecticidal protein Cry9c, had not been approved for human consumption because
      it possessed some characteristics associated with allergenic proteins. However,
      in the fall of 2000 CRY9C DNA was detected in several corn-containing products,
      suggesting that Starlink corn had entered the human food supply. Subsequently,
      consumers, following consumption of corn products, reported a number of adverse
      health events, possibly consistent with allergic reaction. METHODS: To
      investigate the possibility of allergic reactions due to Cry9c in these consumers
      an ELISA test was developed for the purpose of detecting IgE antibodies to Cry9c
      and blood samples were taken from a total of 18 people who self-reported allergic
      reactions. Sera collected prior to the 1996 development of Starlink were used as
      negative controls. RESULTS: None of the adverse event sera were found to be
      reactive with recombinant Cry9c antigen, based on comparison with normal
      controls. Although a known human positive control serum containing IgE specific
      for Cry9c was not available, other controls were incorporated into the ELISA
      protocol, including the use of sera from subjects allergic to other allergens and
      their homologous antigens (cat, grass, peanut) to validate the IgE detection
      reagents. CONCLUSIONS: While the results do not support the likely occurrence of
      allergic reactions to Cry9c, such reactions cannot be ruled out, nor can the
      possibility that sera might react with unique glycosylated epitopes of Cry9c that
      may be expressed in the corn plant/seed.

PMID- 14707464
TI  - Increased levels of IL-2 and IL-4 in stimulated adenoidal lymphocytes of atopic
      children.
AB  - BACKGROUND: The adenoid is involved in the defence against airway pathogens and
      its surface is also exposed to airborne allergens. The knowledge about reactions
      taking place in the lymphatic tissue of this organ is, however, limited. To
      elucidate the influence of atopy we investigated the cellular and cytokine
      profile of in vitro-stimulated adenoid lymphocytes. METHODS: Adenoid tissue cells
      from 13 atopic and 8 non-atopic children were cultured and stimulated with
      ionomycin and 4beta-phorbol 12-myristate 13-acetate. Supernatants were collected
      after 4 and 20 h of stimulation and interleukin-2 (IL-2), IL-4 and interferon
      gamma (IFN-gamma) were analysed by ELISA. Flow cytometry was used to quantify the
      leukocyte markers CD3, CD19, CD25 and HLA-DR. RESULTS: Increased levels of IL-2
      and IL-4 but not IFN-gamma were detected in the supernatants of adenoid cell
      cultures from atopic children after 20 h of stimulation (p < 0.05) and a
      significant correlation with a positive regression between IL-2 and IL-4 was
      found. Atopy was also associated with a greater increase in the percentage of
      CD19-positive B cells after stimulation (p < 0.05). CONCLUSIONS: A difference in
      the reactivity of adenoidal lymphoid cells in children was observed between
      atopic and non-atopic subjects. Atopy was associated with an increased production
      of IL-2 and IL-4 as well as a more pronounced increase of B cells.

PMID- 14707465
TI  - Protein Fv produced during viral hepatitis is an endogenous immunoglobulin
      superantigen activating human heart mast cells.
AB  - Protein Fv, an endogenous protein produced in the liver, is released in
      biological fluids during viral hepatitis. Acute and chronic viral hepatitis can
      be associated with cardiovascular derangements. Protein Fv induced the release of
      histamine, tryptase and the de novo synthesis of prostaglandin D(2) and cysteinyl
      leukotriene C(4) from mast cells isolated from human heart tissue (HHMC). Protein
      Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce
      histamine secretion. The maximal percent histamine secretion induced by protein
      Fv correlated (r(s) = 0.60; p < 0.05) with that induced by anti-IgE, whereas
      there was no correlation between the release caused by proteins Fv and C5a.
      Preincubation of HHMC with protein Fv or anti-IgE caused complete cross
      desensitization to subsequent challenge with heterologous stimulus. HHMC from
      which IgE had been dissociated no longer released histamine in response to anti
      IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv
      induced release. Three human monoclonal IgM V(H)3(+) inhibited protein-Fv-induced
      secretion of histamine from HHMC, whereas monoclonal IgM V(H)6(+) did not inhibit
      the release induced by protein Fv. Protein Fv acts as an endogenous
      immunoglobulin superantigen by interacting with the V(H)3 domain of IgE to induce
      the release of mediators from HHMC.

PMID- 14707466
TI  - A novel mouse model of experimental asthma.
AB  - BACKGROUND: Animal models that mimic the pulmonary features observed in human
      asthma are important tools to study the mechanism(s) of allergen-induced asthma.
      Cockroach and dust mite allergens are two common allergens found in the 'inner
      city' environment. In this study, we examined the interaction between recombinant
      cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain
      (A/J). The tested hypothesis was that there are enhanced effects of exposure to r
      Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice.
      METHODS: Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline)
      controls; adjuvant (alum) controls; r Bla g 2 immunized (0.01-10 microg/mouse), r
      Der f 1 immunized (0.01-10 microg/mouse), and combined immunization with r Der f
      1 (0.05 microg/mouse) and r Bla g 2 (0.0 5 microg/mouse). Mice were immunized at
      days 0 and 7, challenged by oro-tracheal inhalation with r Der f 1 and/or r Bla g
      2 allergen at day 14, and were studied and sacrificed on day 17. Airway
      hyperreactivity was measured by peak airway pressure and airway pressure time
      index (APTI). Differential cell analysis and total proteins in bronchoalveolar
      lavage returns were used to assess airway inflammation and epithelial injury.
      RESULTS: Dose-related statistically significant increases in peak pressure, APTI,
      total cells, eosinophils, epithelial cells, but not total proteins, were induced
      by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose
      related increases in airway total cells, eosinophils, epithelial cells and total
      proteins were observed in r Der f 1 immunized mice. Compared to either allergen
      alone, enhanced airway inflammation and epithelial damage, but not airway
      reactivity, were detected in the combined group. CONCLUSION: This novel mouse
      model will allow investigation of the immunopathogenesis of human asthma and
      should provide insight into the common form of 'inner city asthma'.

PMID- 14707467
TI  - Gene expression analysis of atopic dermatitis-like skin lesions induced in NC/Nga
      mice by mite antigen stimulation under specific pathogen-free conditions.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammation
      characterized by pruritic and eczematous skin lesions usually observed in
      patients with a familial history of atopic diseases, but its exact etiology is
      unclear. An animal model is indispensable for the analysis of the pathogenesis
      and the development of new drugs to treat this disease. Here, we compare changes
      in gene expression profiles in the AD-like skin lesions of NC/Nga or BALB/c mice
      stimulated intradermally by mite antigen under specific pathogen-free (SPF)
      conditions. METHODS: Mite Extract-Dp was injected intradermally into the right
      and left pinnae and into the skin of the back of NC/Nga or BALB/c mice in 2
      places once per 3 days, and the clinical symptoms and the ear thickness were
      measured. On day 14 or day 28 after starting mite extract injection, we collected
      plasma and pinnae from NC/Nga or BALB/c mice. The amount of total immunoglobulin
      E (IgE) in plasma was assayed. We analyzed mRNA transcripts in pinnae using real
      time quantitative PCR for the murine counterparts of several known allergy
      related genes. Moreover, genome-wide gene expression in pinnae from NC/Nga mice
      was analyzed using high-density oligonucleotide arrays (GeneChip, Affymetrix).
      RESULTS: From 2 weeks after stimulation, marked skin inflammation was induced in
      the pinnae of NC/Nga but not BALB/c mice. However, IgE levels in sera rose
      equally in both strains. Quantitative PCR analysis and comprehensive GeneChip
      analysis of the AD-like pinna skin lesions revealed that their development was
      accompanied by changes in expression of more than 1,000 genes. These included
      cytokines, cytokine receptors, proteases, and adhesion molecules. Furthermore,
      genes thus far not reported in association with AD were also affected.
      CONCLUSION: From these results, the NC/Nga mouse model using mite sensitization
      under SPF conditions could be useful for elucidating the mechanisms of AD
      pathogenesis and developing more effective therapy for AD.

PMID- 14707469
TI  - Cytokine production, lymphocyte proliferation and T-cell receptor Vbeta
      expression in primary peripheral blood mononuclear cell cultures from nickel
      allergic individuals.
AB  - BACKGROUND: Clinical history and patch test constitute the two cornerstones in
      the diagnosis of nickel (Ni) allergy. Due to technical and interpretative limits
      of the patch test, the in vitro lymphocyte transformation test (LTT) has been
      developed for confirming contact allergy; however, most studies show an overlap
      in lymphocyte proliferation between Ni-allergic and nonallergic subjects using
      the LTT. The aim of this study was to see if the secretion of cytokines,
      especially interleukin (IL)-10 and IL-17, or the use of T-cell receptor (TCR)
      Vbeta families in Ni-stimulated primary peripheral blood mononuclear cell (PBMC)
      cultures might be more useful for discriminating between allergic and nonallergic
      subjects. METHODS: Ni(2+)-stimulated primary PBMC cultures derived from female
      subjects diagnosed as Ni-allergic (n = 5) or nonallergic (n = 5) on the basis of
      a positive or negative patch test were assessed for cell proliferation by
      tritiated thymidine incorporation and for production of interferon-gamma, IL-4,
      IL-10 and IL-17 in the culture supernatant by ELISA. The immunophenotype and TCR
      Vbeta family affiliation of the Ni(2+)-induced lymphoblasts were determined by
      flow cytometry. RESULTS: Lymphocytes from Ni-allergic individuals challenged with
      a high and a low concentration of Ni showed significantly higher cell
      proliferation than lymphocytes from nonallergic individuals, but all subjects
      showed a positive LTT result (stimulation index >2). We found a significantly
      higher release of IL-10 in Ni(2+)-treated cultures from Ni-allergic compared with
      nonallergic subjects that provided better separation between individuals in the
      two groups than did lymphocyte proliferation. The proliferating lymphoblasts were
      predominantly CD4+, and in 2 of the 5 Ni-allergic subjects, but in none of the 5
      nonallergic subjects, the CD4+ lymphoblasts showed a dominance of TCR-Vbeta17.
      CONCLUSIONS: Determination of IL-10 production in primary PBMC cultures is a
      potentially promising in vitro method for discrimination of Ni allergy in
      females, as compared with cell proliferation.

PMID- 14707468
TI  - Allergen skin test reaction patterns in children (</=10 years old) from atopic
      families suggest age-dependent changes in allergen-IgE binding in early life.
AB  - BACKGROUND: Genetic studies of atopy rely upon evidence of abnormal IgE
      production, usually elevated total IgE or skin prick test (SPT) reactions.
      However, these measures may change with subject age. METHODS: We screened 1,099
      members of atopic families (aged 6-87 years) by serum total IgE and SPT for 14
      allergens. For those SPT negative, we screened for Amb a 1- and Der p 1-specific
      IgE. Der p 1 IgE-Der p 1 allergen binding affinities were done on randomly
      selected subjects. RESULTS: There were significantly fewer atopics </=10 years
      old (69.1%) compared to those >10 years old (75.8%) based upon any SPT-positive
      result. Children </=10 years had fewer SPT-positive reactions and smaller SPT
      wheal reaction areas. Yet, mean total IgE values were comparable to those of the
      older group. Screens for specific IgE showed no differences in proportions of
      atopics (</=10 years old = 83.1% and >10 years old = 82.3%). Among those SPT
      positive for house dust mite extract, there was a positive correlation between
      Der p 1 binding affinity and the wheal area of the house dust mite extract. There
      was a positive correlation between the number of SPT-positive reactions and total
      IgE for both age groups. However, there was only a significant relationship
      between SPT-positive wheal area and total IgE for those >10 years old and no
      apparent relationship between wheal area and total IgE for those </=10 years old.
      CONCLUSION: These results suggest that atopy-specific physiological mechanisms,
      primarily those involving allergen-IgE binding, change during the earliest years
      of life.

PMID- 14707470
TI  - Suckling reduces allergic skin responses and plasma levels of neuropeptide and
      neurotrophin in lactating women with atopic eczema/dermatitis syndrome.
AB  - BACKGROUND: Lactation is associated with an inhibited hypothalamic-pituitary
      adrenal axis response to physical and psychological stress in women and female
      rats. However, suckling also improved mood and calmness in nonatopic lactating
      women. Relaxation by humor reduced allergen-induced skin wheal responses, while
      various forms of stress enhanced those responses in allergic patients. Moreover,
      enhancement and reduction in allergen-induced skin wheal responses are associated
      with up- and down-regulation of plasma levels of substance P (SP) and vasoactive
      intestinal peptide (VIP), respectively. In addition, plasma levels of SP, VIP and
      nerve growth factor (NGF), but not neurotrophin-3 (NT-3), are elevated in
      allergic patients. Therefore, the effects of suckling on allergic responses and
      plasma levels of neuropeptides and neurotrophins were studied in lactating women
      with atopic eczema/dermatitis syndrome (AEDS). METHODS: Before and after
      suckling, allergic skin responses to allergens were studied by skin prick test;
      simultaneously plasma levels of substance P, vasoactive intestinal peptide, nerve
      growth factor and neurotrophin-3 were measured in lactating women with atopic
      eczema/dermatitis syndrome. RESULTS: Suckling reduces allergen-induced, but not
      histamine-induced, skin wheal responses, while holding infants without suckling
      failed to do so. Suckling also reduced plasma levels of SP, VIP and NGF, but not
      NT-3 in these patients, while holding infants without suckling failed to do so.
      CONCLUSIONS: These results indicate that suckling reduces allergic responses with
      a concomitant reduction in plasma levels of SP, VIP and NGF. Collectively,
      suckling may have some implication in the study of maternal allergy in atopic
      patients.

PMID- 14707472
TI  - Modified reduction surgery for adenomyosis. A preliminary report of the
      transverse H incision technique.
AB  - We describe the preliminary clinical results of a modified method of reduction
      surgery for easy approach and effective removal of lesions in women with
      adenomyosis. Old classical reduction surgery was performed in 5 women with
      imaging diagnosis of adenomyosis who were selected retrospectively among 104
      patients undergoing conservative surgery. A transverse H incision method in the
      reduction surgery was applied to 6 of 83 patients wishing to preserve fertility.
      Benefit in operative procedure, complications, patients' compliance, and
      pregnancy outcome were analyzed and compared between 5 women with the classical
      method and 6 women with the H incision method for adenomyosis. No apparent
      difference was observed in the operation time, blood loss and volume of excised
      specimens between these two groups. The major complication of perforation during
      surgery occurred in 2 patients (40%) by the classical method and in only 1
      patient (17%) by the H incision technique. The subjective relief of pain was
      relatively more evident in the modified than in the classical group. There was no
      case of pregnancy in the classical group; however, 1 patient conceived
      spontaneously 4 months after operation by this H incision procedure. Our H
      incision technique may be considered a useful method for an easy surgical
      approach and satisfactory removal of adenomyotic lesions and may be better than
      the old classical method of reduction surgery.

PMID- 14707471
TI  - Acromegaly induced by growth hormone replacement therapy.
AB  - Recombinant human growth hormone (GH) has been shown to be efficacious and safe
      in the treatment of various growth disorders and GH deficiency. We here report a
      61-year-old man with idiopathic hypopituitarism in whom clinically active
      acromegaly developed. Complete GH deficiency had been diagnosed earlier by
      arginine stimulation testing, and therapy with recombinant human GH (maintenance
      dose 2 IU/day) was implemented at the age of 54 years. At presentation, the
      patient's insulin-like growth factor 1 (IGF-1; 439 ng/ml) and insulin-like growth
      factor binding protein 3 (4.3 mg/l) levels were highly elevated. Endogenous GH
      production and pituitary adenoma were excluded. Retrospectively, IGF-1 levels up
      to 621 ng/ml had been documented (but not appreciated) in the preceding 7 years.
      Upon GH dose reduction, the IGF-1 serum levels returned to normal, and the
      patient's clinical status stabilized. No GH receptor polymorphisms were
      identified in the patient's genomic DNA. This observation demonstrates that the
      indiscriminate use of recombinant GH bears the risk of active acromegaly,
      emphasizing the need for long-term patient monitoring programs as integral part
      of GH therapy.

PMID- 14707473
TI  - Misoprostol for cervical ripening and labor induction in pregnancies with
      oligohydramnios.
AB  - The efficacy and safety of misoprostol for cervical ripening and labor induction
      in patients with oligohydramnios was investigated. 57 pregnancies with
      oligohydramnios and 58 cases with a normal amniotic fluid volume (controls) were
      enrolled in this prospective trial. All patients received 50 microg of
      intravaginal misoprostol every 5 h. Primary outcomes were: cesarean section rate;
      induction to delivery time; oxytocin augmentation; uterine hyperstimulation;
      meconium passage; fetal heart rate (FHR) changes; fetal distress requiring
      delivery, and Apgar scores. There were no differences in the mean time to
      delivery, cesarean section rate, oxytocin augmentation or Apgar scores. The mean
      induction to delivery time in oligohydramnios and control groups were, 11 h 43
      min and 11 h 18 min, respectively (p > 0.05). FHR changes were observed in 26.3%
      of oligohydramnios group and 32.7% of control group (p > 0.05). There was no
      statistically significant difference in the cesarean section rate and the uterine
      hyperstimulation between the 2 groups. These data suggest that misoprostol can be
      used as an effective agent for cervical ripening and labor induction in
      pregnancies with oligohydramnios without increasing the risk for perinatal
      outcome, compared to those with normal amniotic fluid volumes.

PMID- 14707474
TI  - Treatment of climacteric symptoms with herbal formulas of traditional Chinese
      medicine.
AB  - Hormone replacement therapy (HRT) is not successful or is contraindicated for the
      treatment of climacteric symptoms in some patients. To investigate whether
      certain herbal formulas of traditional Chinese medicine (Kampo in Japanese) could
      be used as an alternative treatment, a longitudinal 'before and after'
      comparative study was carried out in 18 Japanese women, and the results were
      compared with those of 16 women who underwent HRT. Kampo improved all the
      climacteric symptoms. In contrast, improvement of cold limbs, sleeping disorders,
      shoulder stiffness/lumbago, and fatigue in the HRT group was either not
      significant or of limited extent. In addition, the serum level of estradiol in
      postmenopausal women was raised by the combined use of two Kampo formulas. These
      results suggest that Kampo may be considered an alternative to HRT for the
      treatment of climacteric symptoms, but vigorous monitoring for potential side
      effects of increased estrogen levels in some postmenopausal patients is needed.

PMID- 14707475
TI  - Long-term renal function after HELLP syndrome.
AB  - This study was set up to determine the long-term (5 or more years) renal function
      after HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome
      during pregnancy and to answer the question whether long-term renal follow-up is
      necessary. Women with HELLP syndrome were compared with healthy control subjects
      who delivered their first child during the same period. There was no difference
      between groups for body mass index, serum and urinary creatinine levels,
      creatinine clearance, total urinary protein/creatinine ratio, and urinary
      microalbumin/creatinine ratio. Women who previously had HELLP syndrome had
      significantly higher diastolic and systolic blood pressures. Women with HELLP
      syndrome do not need continued renal follow-up, but have higher systolic and
      diastolic blood pressures, even 5 years after HELLP syndrome.

PMID- 14707476
TI  - [Unspecified stimuli--a classic misunderstanding].

PMID- 14707477
TI  - [Quality assurance in the teaching of medical students illustrated by the example
      of spa therapy for rheumatic diseases].
AB  - BACKGROUND: The currently employed methods for quality assurance in student
      education are frequently considered as being inadequate. In the present study the
      request to plan a budget for the treatment of patients with ankylosing
      spondylitis is presented as an additional method to assess the influence of a
      teaching course on the student's attitude towards certain interventions. How
      would medical students distribute financial resources for the treatment of
      patients with ankylosing spondylitis? Does a course 'Excursion to a Spa' lead to
      changes in budgeting by the student? MATERIAL AND METHODS: Before and after a 4
      day excursion to Bad Gastein (health resort primarily for patients with rheumatic
      diseases) to become better acquainted with the local treatment modalities medical
      students in semester 8.4 +/- 3.8 (5th year in medical school) were asked how they
      would distribute a fixed sum of EUR 5,000.- (= 100%) for a prospective period of
      5 years over 9 given forms of treatment in a patient with ankylosing spondylitis
      in order to provide optimal improvement of the disease and quality of life.
      RESULTS: Before the excursion the students distributed the budget as follows:
      drug therapy 15%, spa therapy 17%, physical therapy 14%, exercise therapy 19%,
      massage therapy 11%, unconventional therapies 5%, psychological therapy 7%,
      changes in the household environment 8%, private pleasure 4%. After the excursion
      to the spa the medical students assigned more financial means on spa therapy (p =
      0.024, Wilcoxon test) and unconventional therapies (p = 0.015). CONCLUSION:
      Creating a budget for a defined disease appears to be a useful instrument for
      assessing the influence of a teaching course on medical students' attitude
      towards certain interventions and for detecting imbalances in the presentation of
      therapy procedures or discrepancies between the presentation and the aims of
      teaching.

PMID- 14707478
TI  - [Use of complementary/alternative therapy methods by patients with breast
      cancer].
AB  - BACKGROUND: Complementary/alternative medicine (CAM) is gaining increasing
      importance especially in the treatment of patients with breast carcinoma. The
      purpose of this analysis was to investigate the prevalence of CAM in patients
      with breast carcinoma, to statistically describe the preparations and therapies
      used, and to determine the reasons for their use, the source of information and
      the individual perception. PATIENTS AND METHODS: The statements of 203 patients
      with breast carcinoma who underwent radiotherapy were analyzed. The median age
      was 54 years (range 38-77 years). All patients underwent surgery as first
      therapy. 36 patients received a second-line radiotherapy because of metastases
      (27 patients) or local recurrence (9 patients). RESULTS: 159 patients (78%)
      stated to carry out an additional treatment. 31 out of the 36 patients with
      metastases or local recurrence used CAM. Vitamin preparations (67%), mistletoe
      therapy (59%), and mineral preparations (33%) were used most frequently. 70% of
      the patients used a combination of two or more preparations/therapies. The most
      cited reason for using CAM was the aim of increasing quality of life (28%) and
      improving the immune system (27%). 72% stated an improvement of their individual
      perception. The main source of information was the general practitioner or the
      gynecologist. CONCLUSION: The radiotherapist has to take these
      complementary/alternative therapies into consideration; their importance should
      be evaluated in further studies.

PMID- 14707479
TI  - Inhibition of (-)-propranolol hydrochloride by its enantiomer in white mice.
AB  - BACKGROUND: This study is based on the hypothesis, that the toxic or
      physiological effects of an optical isomer may be counteracted or reversed by the
      administration of a potentized preparation of one of its stereoisomers. In the
      present study the enantiomer was used. METHODS: 154 ICR conventional mice were
      used. 77 mice were administered (R)-(+)-propranolol HCl homeopathic potency prior
      to and during the experiment, and the other 77 were administered
      indistinguishable placebo. On the day of the experiment the mice were sedated
      with intraperitoneal Rometar. Once sedated they were injected intraperitoneally
      with the LD50 dose of (S)-(-)-propranolol HCl. RESULTS: The end point for
      statistical analysis was the difference in survival between the placebo and
      treatment mice. The odds ratio for survival of treatment mice relative to placebo
      mice was 1.64. The hypothesis of equal survival proportions gave a chi-square of
      2.0916 (1 degree of freedom), which has a p-value of 0.1481. The analysis was
      then adjusted for mouse weight and intraperitoneal (-)-propranolol dosage using a
      logistic regression (LR) model. The LR treatment odds ratio was 2.017 and the LR
      treatment chi-square was 2.8864 (1 degree of freedom), which has a p-value of
      0.0893. Consequently we accept the null hypothesis of no treatment effect on
      survival. The odds ratio estimates show that the treatment mice are 2.02 times
      more likely to survive than placebo mice, but this was not statistically
      significant with p = 0.089. Nine percent more treatment mice survived than
      placebo mice. The investigators accustomed to handling rodents noted that mouse
      recovery seemed substantially faster in the treatment mice than in the placebo
      mice.

PMID- 14707480
TI  - Sensitive flow cytometric method to test basophil activation influenced by
      homeopathic histamine dilutions.
AB  - OBJECTIVE: In an experimental setting, human basophil degranulation was triggered
      by anti-IgE to measure the effects from homeopathic solutions in an in-vitro cell
      system. A 3-color flow cytometric method with enhanced accuracy was established.
      As an example we looked at the influence of histamine on anti-IgE activation of
      basophils. METHODS: Basophils were identified in the flow cytometer by their
      physical properties in the forward and side scatter light depiction and by gating
      on CD2(-), CD14(-), CD16(-), CD19(-), HLA-DR(-) negative and CD123-positive
      cells. CD63 expression on the cell surface of the anti-IgE-activated basophils
      served as an activation marker. RESULTS: With this method we were able to study
      basophil function of the 0.6-3.9% basophils out of the mononuclear blood cell
      fraction and to document their activation status upon anti-IgE activation.
      Optimal activation occurs at 0.6 microg/ml final anti-IgE concentration; not less
      than 10,000 basophils have to be counted per batch to reduce the variation of the
      measurement. The fixation method was able to stabilize activation for two days.
      After investigation and reduction of the source of measurement variability, an
      unequivocally inhibited basophil activation was documented in a partly optimized
      system with homeopathic dilutions of histamine (10(-22)M, 10(-23)M, 10(-24)M, and
      10(-25)M histamine). Dilutions greater than 10(-20)M histamine (Avogadro's number
      6.02 x 10(23)) account for less than 1.36 molecules of histamine in the test
      sample, indicating a true homeopathic effect. CONCLUSIONS: This test system is
      adequate for studying the effects of highly diluted mediators on basophil
      activation by anti-IgE. The systematic application of this experimental
      arrangement is recommended to study the effects of homeopathic dilutions on
      basophils.

PMID- 14707481
TI  - The Alexander technique: a systematic review of controlled clinical trials.
AB  - AIM: Alexander technique (AT), a process of psychophysical re-education, is being
      promoted for a range of medical conditions. This systematic review is aimed at
      critically evaluating the evidence for or against the effectiveness of AT.
      METHODS: Computerized literature searches were performed in five databases to
      locate all controlled clinical trials of AT in any human condition. Data were
      extracted independently by two reviewers according to pre-defined criteria. The
      information was summarized in tabular and narrative form. The methodological
      quality of the primary studies was assessed using the Jadad score. RESULTS: Four
      clinical trials met our inclusion/exclusion criteria. Only two of these trials
      were methodologically sound and clinically relevant. Their results are promising
      and imply that AT is effective in reducing the disability of patients suffering
      from Parkinson's disease and in improving pain behaviour and disability in
      patients with back pain. CONCLUSION: The few controlled clinical trials of AT
      yield encouraging albeit not convincing evidence. AT deserves to be studied in
      more detail.

PMID- 14707482
TI  - [Stress, adaptation, and self-organization: balancing processes facilitate health
      and survival].
AB  - BACKGROUND: Stress is of growing significance not only in established industrial
      countries. Preventive medical aspects are becoming important in association with
      the stress phenomenon. OBJECTIVE: Discussing the correlation between stress and
      health (or disease). Does a state of dynamic balance play a role in the context
      of stress, allostasis, adaptation, and self-organization? What kind of influence
      do balancing processes have on health and survival? RESULTS: Stress itself is
      neither harmful nor healthy. Instead, it represents a fundamental biological
      principle that is associated with vivacity and that facilitates adaptation,
      dynamic balance, self-organization, and survival within a constantly changing
      environment. Stress may also be of significance for biological evolution. A
      crucial part of the physiological concept is the autoregulatory stress response.
      Thereby, stress may enhance biological creativity and health, but may also lead
      to allostatic load and disease. Not only exogenous stressors, but also the
      subject itself decide upon the individual stress outcome. CONCLUSIONS: Dynamic
      balances characterize life and survival. Further, they are crucial for health
      processes. Stress may facilitate a 'healthy' balance or enhance disease processes
      likewise. Hence, the subjective inner structure or self-organization of an
      organism determines--in addition to exogenous factors--individual consequences of
      stress. Therefore, prevention should strengthen the subject and amplify self
      capacity and responsibility. Professional stress-management strategies or
      integrative/mind-body medical programs may be helpful.

PMID- 14707483
TI  - Heparin inhibits the reconstituted plasma membrane Ca(2+)-ATPase from porcine
      brain synaptosome.
AB  - Heparin has been shown to be involved in the regulation of cellular Ca(2+) by
      binding to many proteins with high affinity. Here we examined the effects of
      heparin on the plasma membrane Ca(2+)-ATPase from porcine brain synaptosome. Our
      results showed that heparin dramatically inhibited the ATP hydrolysis and Ca(2+)
      uptake in the presence and absence of calmodulin. Together with controlled
      proteolysis by trypsin, we concluded that the calmodulin-binding domain of the
      plasma membrane Ca(2+)-ATPase was less important for the heparin inhibition.
      Excess phosphatidylserine was able to eliminate the heparin inhibition. We
      observed that Ca(2+) affinity kept no obvious changes, but the ATP affinity of
      plasma membrane Ca(2+)-ATPase was apparently decreased in the presence of
      heparin. Our results indicated that heparin had little effects on ATP or Ca(2+)
      binding sites of the enzyme.

PMID- 14707484
TI  - In vivo glycosylation of MUC1 in airway epithelial cells.
AB  - The O-glycans that decorate mucin glycoproteins contribute to the biophysical and
      biochemical properties of these molecules and hence their function as a barrier
      and lubricant on epithelial surfaces. Alterations in mucin O-glycosylation in
      certain diseases may contribute to pathology. It is known that both the host cell
      type and the amino acid sequence of the mucin tandem repeat contribute to the O
      glycosylation of a mucin molecule. We expressed an epitope-tagged MUC1 mucin cDNA
      construct in the airway cell line 16HBE14o- and the colon carcinoma cell line
      Caco2 and used Fast Atom Bombardment Mass Spectrometry to evaluate the
      contribution of the host cell to differences in O-glycosylation of a single
      mucin. Many of the glycans detected on the MUC1 mucin were common to both cell
      types, as would be predicted from biosynthetic constraints. However, MUC1
      synthesized in the airway cell line showed comparatively low levels of
      sialylation but carried a range of oligo-N-acetyllactosamine structures that were
      not seen in the colon carcinoma cell line.

PMID- 14707485
TI  - The influence of ovarian steroids on ovine endometrial glycosaminoglycans.
AB  - The ovine endometrium is subjected to cyclic oscillations of estrogen and
      progesterone in preparation for implantation. One response to fluctuating
      hormonal levels is the degree of hydration of the tissue, suggesting cyclical
      alterations in glycosaminoglycan/proteoglycan content. The aim of the present
      study was to quantitate and characterize glycosaminoglycans in the ovine
      endometrium during estrogen and progesterone dominant stages. Endogenous
      endometrial glycosaminoglycan content was determined by chemical analysis and
      characterized by enzyme specific or chemical degradation. [(35)S]-sulphate and
      [(3)H]-glucosamine labeled proteoglycans/glycosaminoglycans were extracted by
      cell lysis or with 4M guanidine-HCl. Extracts were purified by anion exchange and
      gel chromatography and characterized as above. Estrogen and progesterone dominant
      endometrium contained 3.2 +/- 0.1 and 2.1 +/- 0.1 mg endogenous
      glycosaminoglycan/g dehydrated tissue, respectively. Characterization of
      endogenous glycosaminoglycan showed chondroitin sulphate and hyaluronan
      contributing over 80%. The major difference between hormonal dominant tissue was
      a higher estrogenic hyaluronan percentage and a higher progestational keratan
      sulphate percentage (p < 0.001). Estrogen dominant tissue incorporated 1.6-1.9
      fold more radiolabeled proteoglycans/glycosaminoglycans (p < 0.001). Analysis of
      newly synthesized proteoglycans/glycosaminoglycans revealed a heparan/chondroitin
      sulphate ratio of 1:2.2-2.5. Keratan sulphate was not detected. Estrogenic
      hyaluronan was 1.6 fold greater in [(3)H]-labeled tissue. Analysis of labeled
      proteoglycans/glycosaminoglycans revealed two size classes with apparent
      molecular weights >2.0 x 10(6) and 0.8-1.1 x 10(5) and a charge class eluting
      between 0.1-0.5 M NaCl. The greater glycosaminoglycan content (particularly
      hyaluronan) and synthesis in estrogen dominant tissue supports a role for steroid
      hormones in endometrial glycosaminoglycan/proteoglycan regulation and consequent
      tissue hydration. It also suggests a role for these macromolecules in endometrial
      function and possibly the implantation process.

PMID- 14707486
TI  - Characterization of LPS mutants of peanut specific Bradyrhizobium (GN17).
AB  - Two mutants of Bradyrhizobium sp. (Arachis) strain GN17 having altered
      lipopolysaccharide (LPS) composition were isolated upon random Tn5 mutagenesis to
      study their binding with peanut root lectin (PRA II). These mutant strains
      designated as GN17M1 and GN17M2 produced rough colonies and showed
      autoagglutination. Flow cytometric analyses indicated that strain GN17M1 bind to
      PRA II with highest efficiency. Both the mutants synthesized only high molecular
      weight lipopolysaccharides as observed by silver staining of polyacrylamide gel.
      The LPSs from both the mutants cross-reacted with anti-GN17 LPS, however, GN17M1
      LPS showed 3 times higher cross-reactivity as detected by ELISA. Carbohydrate
      analysis by high performance anion exchange chromatography (HPAEC) showed that
      glucose was the major constituent of the purified LPS from the parent strain
      whereas mannose appeared as major component in the GN17M2 LPS. Equivalent amount
      of glucose and galactosamine with significant amount of mannose and galactose was
      the characteristics of the GN17M1 LPS. Purified LPS from GN17M1 and GN17M2 were
      respectively 17 and 10 times more potent inhibitors of PRA II activity than that
      of parent strain GN17. Similar binding efficiencies of the mutant LPS towards PRA
      II was also observed by ELISA. The results of this study indicate that the
      composition and the arrangement of the LPS are crucial for lectin binding.

PMID- 14707487
TI  - Sulfatide is associated with insulin granules and located to microdomains of a
      cultured beta cell line.
AB  - Previous studies using pancreas from various mammals and freshly isolated islets
      from rat pancreas have provided evidence supporting possible involvement of the
      glycosphingolipid sulfatide in insulin processing and secretion. In this study,
      sulfatide expression and metabolism in the beta cell line RINr1046-38 (RIN-38),
      commonly used as a model for beta cell functional studies, were investigated and
      compared with previous findings from freshly isolated islets. RIN-38 cells
      expressed similar amounts (2.7 +/- 1.1 nmol/mg protein, n = 19) of sulfatide as
      isolated rat islets and also followed the same metabolic pathway, mainly through
      recycling. Moreover, in agreement with findings in isolated islets, the major
      species of sulfatide isolated from RIN-38 cells contained C16:0 and C24:0 fatty
      acids. By applying subcellular isolations and electron microscopy and
      immunocytochemistry techniques, sulfatide was shown to be located to the
      secretory granules, the plasma membrane and enriched in detergent insoluble
      microdomains. In the electron microscopy studies, Sulph I staining was also
      associated with mitochondria and villi structures. In conclusion, RIN-38 cells
      might be an appropriate model, as a complement to isolated islets where the
      amount of material often limits the experiments, to further explore the role of
      sulfatide in insulin secretion and signal transduction of beta cells.

PMID- 14707488
TI  - Determination of UDP-N-acetylglucosamine: beta-D-mannoside-1,4-N
      acetylglucosaminyltransferase-III in patients sera with chronic hepatitis and
      liver cirrhosis using a monoclonal antibody.
AB  - The glycoprotein UDP-N-acetylglucosamine: beta-D-mannoside-1,4-N
      acetylglucosaminyltransferase-III (GnT-III) catalyzes the addition of N
      acetylglucosamine via a beta-1, 4-linkage to the beta-linked mannose of the
      trimannosyl core of N-linked glycans. It has been reported that the expression of
      GnT-III increases in many oncogenically transformed cells and human
      hepatocellular carcinoma (HCC) tissues, and GnT-III enzyme activity in serum can
      be used for the detection and monitoring of primary hepatomas and hepatocellular
      carcinomas. A solid-phase enzyme-linked immunosorbent sandwich assay in which a
      polyclonal antibody (PAb) to aglycosylrecombinant GnT-III (AGR-GnT-III) and a
      monoclonal antibody (mAb) are employed as a capture protein and probe protein,
      respectively, is described. The sensitivity of the PAb-mAb sandwich assay, as
      determined by the dose-response effect for AGR-GnT-III, was 10 ng/ml. This assay
      was specific for GnT-III and did not detect beta-1, 6-N
      acetylglucosaminyltrasferase-V (GnT-V). AGR-GnT-III concentrations in 377 serum
      specimens were determined by the PAb-mAb sandwich assay and the results were
      analyzed based on the disease category, using 1.99 microg/mL (AGR-GnT-III) as a
      cut-off value. The AGR-GnT-III level of 61 normal serum samples was 0.57 +/- 0.71
      microg/ml (mean +/- SD). The results revealed an elevation in serum AGR-GnT-III
      levels in 60 of 86 patients (3.03 +/- 2.04 microg/ml) with liver cirrhosis (LC)
      and 86 of 91 patients (2.73 +/- 0.59 microg/ml) with chronic hepatitis (CH). By
      contrast, 3 of 61 normal subjects, 9 of 34 patients (1.02 +/- 1.03 microg/ml)
      with acute hepatitis and 8 of 38 patients (1.79 +/- 0.56 microg/ml) with a
      variety of non-hepatic diseases exhibited a slight increase above the cut-off
      value. These results indicate that serum AGR-GnT-III levels are elevated
      predominantly in LC or CH cases. Serum AGR-GnT-III concentration, as measured by
      the developed PAb-mAb sandwich assay, may be a useful differential marker as a
      diagnostic aid for CH and/or LC and warrants further investigations with expanded
      serum panels.

PMID- 14707489
TI  - Synthesis of a targeting drug for antifibrosis of liver; a conjugate for
      delivering glycyrrhetin to hepatic stellate cells.
AB  - The neoglycoproteins that consist of human serum albumin (HSA) modified with
      mannose 6-phosphate ([M6P]x-HSA) were synthesized, and they showed high binding
      property to hepatic stellate cells (HSC) by immunohistochemical analysis. In
      addition, an increased substitution (X) of 6-phosphated mannose (M6P) was
      associated with an increased accumulation in HSC. So the [M6P]x-HSA might be a
      carrier to deliver drugs to HSC. The antifibrotic drug, glycyrrhetin, was chosen
      to conjugate to M6P(26)-HSA. The result suggests there were 6 approximately 7
      glycyrrhetin molecules having been conjugated to the carrier. Targeting
      glycyrrhetin to HSC might reduce its adverse affects and increase the efficacy.

PMID- 14707491
TI  - The antiangiogenic agent Neovastat (AE-941) stimulates tissue plasminogen
      activator activity.
AB  - The plasminogen activator/plasmin system represents a key component of the
      proteolytic machinery underlying angiogenesis. In this work, we investigated the
      effect of Neovastat (AE-941), a naturally occurring multifunctional
      antiangiogenic agent that is currently in Phase III clinical trials, on tissue
      and urokinase plasminogen activator activities. We found that in vitro, Neovastat
      at 100 microg/ml markedly stimulates t-PA-mediated plasmin generation, while it
      slightly inhibits the generation of plasmin mediated by uPA. The stimulatory
      effect of Neovastat on t-PA activity was markedly increased by a heat treatment,
      resulting in a 15-fold increase in the rate of activation of plasminogen.
      Neovastat did not directly stimulate the activity of t-PA or plasmin towards
      exogenous substrates, suggesting that its effect requires the presence of
      plasminogen. Accordingly, kinetic analysis showed that Neovastat increases both
      the k(cat) of t-PA as well as its affinity for plasminogen by 10-fold. The
      stimulation of t-PA activity by Neovastat was also correlated with a direct
      interaction of Neovastat with plasminogen as monitored by the surface plasmon
      resonance technology. Overall, these results identify Neovastat as a potent
      stimulator of t-PA-dependent activation of plasminogen, further emphasizing its
      pleiotropic mechanism of action on several molecular events involved in
      angiogenesis.

PMID- 14707490
TI  - Inhibition of cell growth, induction of apoptosis and mechanism of action of the
      novel platinum compound cis-diaminechloro-[2-(diethylamino) ethyl 4-amino
      benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate.
AB  - Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride
      platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine
      complex obtained from the synthesis of cisplatin and procaine. In this paper we
      analyzed, adopting a disease-oriented strategy, the tumour selectivity of this
      compound, its ability to induce apoptosis and its mechanism of interaction with
      DNA. The inhibition of cell proliferation was evaluated by the MTT assay using a
      panel of 51 tumour cell lines. Some of them were also evaluated for the induction
      of apoptosis by 4'-6-diamidine-2'-phenylindole (DAPI) staining, Western blot of
      p53 protein and agarose gel electrophoresis of ladder DNA. Finally, interstand
      cross-links (ISCL) were evaluated by ethidium bromide fluorescence technique.
      When evaluated by the MTT assay, DPR showed a high selective activity for
      neuroblastoma, small cell lung cancer (SCLC), ovarian cancer and leukemia cell
      lines. The comparison of mean graphs of DPR and cisplatin suggested that our
      compound possesses a mechanism of action similar to that, at least in part, of
      its parent compound. Moreover, DPR showed itself to be a good trigger of
      programmed cell death, as demonstrated by DAPI staining, activation of p53
      protein and agarose gel electrophoresis of ladder DNA. Finally, the study of the
      formation of ISCLs demonstrated that DPR, despite being a monofunctional platinum
      compound, is able to form bifunctional adducts through the release of procaine
      residue. Data presented here suggest that DPR is an antitumour agent able to
      trigger apoptosis, and that it is endowed with a peculiar mechanism(s) of action
      and a special selective activity against two tumours, namely neuroblastoma and
      SCLC, which are still characterized by a low incidence of long-term survivors.

PMID- 14707492
TI  - Recent advances in brain tumor therapy: local intracerebral drug delivery by
      polymers.
AB  - New approaches to malignant glioma are being actively investigated. Local drug
      delivery directly to the site of the tumor is one novel approach that has been
      approved by the US FDA and other regulatory agencies worldwide. This agent,
      Gliadel, delivers the chemotherapeutic drug carmustine (BCNU) from a
      biodegradable polymer placed in the resection cavity after brain tumor surgery.
      Gliadel represents the first clinical application of polymer delivery for brain
      tumors, but the potential for this new methodology is far greater. In this
      review, we will briefly summarize the development of Gliadel from a laboratory
      idea to its current role as an approved treatment for gliomas. Then we will
      present the most recent work being done to expand the potential benefits of
      polymeric delivery for brain tumors. This work includes trials for its use as the
      initial therapy for gliomas, as well as its use against metastasis. Further
      clinical trials exploring the maximum-tolerated dose and the combination of
      Gliadel with systemic chemotherapeutic treatments such as temozolamide and O(6)
      benzylguanine will be reviewed. Finally, we will present preclinical work on the
      efficacy of polymeric methods for delivering other chemotherapeutic agents, and a
      variety of novel compounds that modify brain tumor biology. This latter work
      represents potential future clinical applications of local polymeric drug
      delivery to the brain and other sites where cancers can occur.

PMID- 14707493
TI  - Population pharmacokinetics of sibrotuzumab, a novel therapeutic monoclonal
      antibody, in cancer patients.
AB  - Population pharmacokinetics of sibrotuzumab, a humanized monoclonal antibody
      directed against fibroblast activation protein, were determined after multiple
      intravenous infusions of dosages ranging from 5 mg/m(2) to an absolute dose of
      100 mg, in patients with advanced or metastatic carcinoma. In total, 1844 serum
      concentrations from 60 patients in three Phase I and II clinical studies were
      analyzed. The structural model incorporated two disposition compartments and two
      parallel elimination pathways from the central compartment, one linear and one
      nonlinear. Finally estimated pharmacokinetic parameters (%RSE) were: linear
      clearance CLL 22.1 ml/h (9.6), central distribution volume V1 4.13l (3.7),
      peripheral volume V2 3.19l (8.8), inter-compartmental clearance Q 37.6 ml/h
      (9.6); for the nonlinear clearance Vmax was 0.0338 mg/h (25) and Km 0.219
      microg/ml (57). At serum concentrations between approximately 20 ng/ml and 7
      microg/ml, the effect of the nonlinear clearance on pharmacokinetics was marked.
      Only at >7 microg/ml did CLL dominate overall clearance. Interindividual
      variability was 57% for CLL, 20% for V1 and V2, and 29% for Vmax and was larger
      than the inter-occasional variability of 13%. Of the many investigated patient
      covariates, only body weight was found to contribute to the population model. It
      significantly affected CLL, V1, V2 and Vmax resulting in marked differences in
      the model-predicted concentration-time profiles after multiple dosing in patients
      with low and high body weights. In conclusion, a robust population
      pharmacokinetic model was developed and evaluated for sibrotuzumab, which
      identified a possible need to consider body weight when designing dosage regimen
      for future clinical cancer trials.

PMID- 14707494
TI  - A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily
      for five days every three weeks to patients with metastatic adenocarcinoma of the
      colon or rectum.
AB  - BACKGROUND: To evaluate the antitumor activity, toxicities, and pharmacokinetics
      (PK) of DX-8951f administered as a 30-min infusion daily for 5 days every 3 weeks
      in patients with fluorouracil-resistant metastatic colorectal carcinoma. PATIENTS
      AND METHODS: Sixteen patients were enrolled. All had metastatic colorectal
      carcinoma resistant to or progressing after chemotherapy containing 5
      fluorouracil and no prior chemotherapy with camptothecin derivatives. DX-8951f
      was administered until disease progression or unacceptable toxicity. Responses
      were assessed after every two courses. RESULTS: Fifteen patients were evaluable.
      Fifty-one courses of therapy were delivered (median 2). Responses were one minor
      response, six stable disease, and eight progressive disease. The principal
      adverse event was neutropenia, with grade 3 and 4 toxicities in three and eight
      patients, respectively. Non-hematologic toxicities were mild to moderate; the
      most common were fatigue, nausea, and diarrhea. Plasma concentrations of DX-8951
      were well described using a linear two-compartment PK model. There was no
      evidence of nonlinearity in the elimination of PK or auto-inhibition or induction
      of DX-8951 clearance over the 5 days of administration. CONCLUSIONS: DX-8951f at
      this dose and schedule had no significant activity in this patient population.
      The toxicity profile, mainly hematologic, was consistent with previous reports.
      The clearance and volume of distribution were not different from those previously
      reported.

PMID- 14707495
TI  - Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone
      dihydrochloride and low dose CHOP chemotherapy: results of a phase II study.
AB  - PURPOSE: To evaluate the response and side effects of combination therapy with
      low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non
      Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS
      NHL). METHODS: Eighteen patients newly diagnosed with intermediate or high-grade
      AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350
      mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and
      prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone
      dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28
      day treatment cycle. RESULTS: Seventeen males and one female patient were
      accrued. Twelve patients had high-grade pathologies while the remainder had an
      intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte
      count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining
      illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a
      complete remission and 5 (35%) a partial remission. The median failure free and
      overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was
      hematologic with grade 3 or 4 neutropenia in 72%; two patients died of
      neutropenic sepsis. CONCLUSIONS: Mitoguazone in combination with low dose CHOP is
      a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49
      95%). These preliminary results suggest no major improvement in terms of response
      over use of CHOP without mitoguazone.

PMID- 14707496
TI  - A phase II study of 9-nitro-camptothecin in patients with previously treated
      metastatic breast cancer.
AB  - AIMS: This Phase II study was conducted to determine the efficacy and toxicity of
      9-nitro-camptothecin (9-NC) in patients with previously treated metastatic breast
      cancer. Pharmacokinetic samples were obtained to investigate the correlation of
      plasma 9-NC exposure with clinical response and toxicity. PATIENTS AND METHODS:
      Eligible patients had histologically confirmed metastatic breast cancer with
      measurable or evaluable disease. Patients must have received one or two prior
      chemotherapy regimens for metastatic disease. 9-NC was given orally, 1.5
      mg/m(2)/day for 5 days each week; response was assessed every 8 weeks.
      Pharmacokinetic samples were obtained on day 1 of weeks 1 and 5. RESULTS:
      Eighteen patients were enrolled between September 1999 and May 2000; seventeen
      patients were evaluable for response. The most common toxicities were nausea,
      vomiting, urinary symptoms, fatigue and diarrhea. No objective responses were
      observed; six patients had stable disease. 9-NC apparent clearance ranged from
      0.57 to 55.08 L/h (median 5.91 L/h); 9-NC area under the curve ranged from 38 to
      2130 ng/ml x h (median 377 ng/ml x h). There was no relationship between
      pharmacokinetic parameters and individual patient toxicity. CONCLUSION: 9-NC has
      limited activity in patients with previously treated metastatic breast cancer.
      Though 9-NC has substantial pharmacokinetic variability in this patient
      population; no correlation was found between pharmacokinetic variables and
      toxicity.

PMID- 14707497
TI  - Phase II study of interferon gamma in malignant carcinoid tumors (E9292): a trial
      of the Eastern Cooperative Oncology Group.
AB  - PURPOSE: To determine the safety and efficacy of treatment with gamma interferon
      (IFNgamma) in patients with metastatic carcinoid tumor. PATIENTS AND METHODS: 51
      patients were enrolled on this Phase II Eastern Cooperative Oncology Group (ECOG)
      study. Seventy five percent of them had hormonally active tumors. Treatment
      consisted of IFNgamma subcutaneously at a daily dose of 0.1 mg/m(2). Patents were
      evaluated for toxicity weekly for the first month and monthly thereafter;
      response was determined radiologically every 8 weeks. RESULTS: Patients received
      treatment with IFNgamma for a median of 17.9 weeks (range 2-175). Toxicity was
      generally mild and expected: 61% experienced noninfected fever and 21% developed
      granulocytopenia. Three patients (6%) had a partial response; there were no
      complete responses. Median time to progression was 5.5 months (95% confidence
      interval 3.9-11.1). The 1-year progression free rate was 28% (13.4-43.4%). Median
      survival was 42 months, with a 1-year survival rate of 67% (53.3-80%).
      DISCUSSION: This Phase II study demonstrated that therapy with IFNgamma in
      patients with metastatic carcinoid tumor was well-tolerated, but did not produce
      significant antitumor effects. The overall results were somewhat comparable to
      those previously seen with alpha interferons as well as cytotoxic drugs.

PMID- 14707498
TI  - Subcutaneously administered recombinant human interleukin-2 and interferon alfa
      2a for advanced breast cancer: a phase II study of the Cancer and Leukemia Group
      B (CALGB 9041).
AB  - New and more effective treatments are needed for metastatic breast cancer. This
      study aimed to determine the effectiveness of a combination of subcutaneously
      administered recombinant human interleukin-2 (rIL-2), 1.5 MU/m(2) for 5
      consecutive days repeated for 3 weeks, and interferon alpha-2a (IFN), 7.5
      MU/m(2), administered subcutaneously three times per week. Women who had
      previously received 1-2 prior chemotherapy regimens for measurable inoperable,
      recurrent, or metastatic breast cancer were eligible. Of 40 patients accrued to
      the study, 32 were evaluable for response assessment. Toxicities were frequent
      but manageable. The most common grade 3 and 4 toxicities were lymphopenia (17%)
      and malaise/fatigue (24%). There were no complete responses, one partial response
      (3%), and six patients with stable disease (19%). Of the seven patients with
      partial response or stable disease, all had tumors that expressed hormone
      receptors. The median survival was 8.9 months and all patients have died. Good
      performance status was the most important predictor of survival. In this group of
      women with metastatic breast cancer, the overall prognosis was poor. This
      combination of rIL-2 and IFN was ineffective.

PMID- 14707500
TI  - Use of ITS rDNA for discrimination of European green- and brown-banded sporocysts
      within the genus Leucochloridium Carus, 1835 (Digenea: Leucochloriidae).
AB  - Transmission of Leucochloridium species to their definitive avian hosts may be
      facilitated by the rhythmic movement of coloured sporocyst broodsacs in the
      ocular tentacles of infected snails. These broodsacs resemble caterpillars and by
      enticement increase the probability of predation by birds. Broodsac banding
      pattern and colour (green, yellow to red/brown) have traditionally formed part of
      the taxonomic criteria for the genus. In this study, sequence divergence of the
      5.8S rDNA gene and associated internal transcribed spacers (ITS1 and ITS2) in two
      of the most frequently observed Leucochloridium taxa from Europe is related to
      broodsac type based on colour and banding pattern. The present green-banded
      broodsac (L. paradoxum Carus, 1835) and brown-banded broodsac forms (L. variae
      McIntosh, 1932) differ in ITS sequence by 6.8%, confirming their distinctness. No
      intraspecific differences were noted within each colour morph in specimens
      collected from Poland, Denmark or Norway, indicating that a single taxon of each
      type occurs in Europe. The significance of these findings to our understanding of
      metapopulation dynamics and evolutionary ecology of Leucochloridium is discussed.

PMID- 14707499
TI  - Gemcitabine and cisplatin for patients with metastatic or recurrent esophageal
      carcinoma: a Southwest Oncology Group Study.
AB  - PURPOSE: Experimental data, both in vivo and in vitro, suggest that the
      combination of gemcitabine and cisplatin acts synergistically. Within the
      Southwest Oncology Group, we designed a Phase II trial to test this chemotherapy
      combination for patients with esophageal cancer. EXPERIMENTAL DESIGN: Patients
      with metastatic or recurrent esophageal cancer were treated with gemcitabine 1000
      mg/m(2) on days 1, 8, and 15, and cisplatin 100 mg/m(2) on day 15. Cycles were
      repeated every 28 days. The statistical endpoint was overall survival. RESULTS:
      Sixty-four eligible patients were accrued from 37 institutions. Twenty-six
      percent of patients had prior chemotherapy. The treatment was generally well
      tolerated, with the most common toxicity being neutropenia in 31% of patients.
      All 64 patients have died. Survival at 3 months was 81%, and at 1 year was 20%.
      Median survival was 7.3 months. CONCLUSIONS: This regimen is tolerable palliative
      option for patients with metastatic esophageal cancer.

PMID- 14707501
TI  - Synonymy of Boophilus Curtice, 1891 with Rhipicephalus Koch, 1844 (Acari:
      Ixodidae).
AB  - Recent molecular and morphological studies of the genera Rhipicephalus Koch, 1844
      and Boophilus Curtice, 1891 revealed that the five species of Boophilus make the
      genus Rhipicephalus paraphyletic. Thus, Rhipicephalus Koch, 1844 is not a
      monophyletic (natural) lineage and some species of Rhipicephalus are more closely
      related to the species of Boophilus than to other species of Rhipicephalus. Here,
      we revise these genera: Boophilus is synonymised with Rhipicephalus, and
      Rhipicephalus (sensu lato) (including Boophilus) is redefined. By synonymising
      Boophilus with Rhipicephalus, we have changed the nomenclature so that it
      reflects our understanding of the phylogeny of these ticks. Boophilus is retained
      as a subgenus of Rhipicephalus, so the synonymy of Boophilus with Rhipicephalus
      does not result in the loss of the name Boophilus. In addition, Rhipicephalus is
      a well-known genus and the change proposed is simple -- all five species of
      Boophilus become members of Rhipicephalus (Boophilus).

PMID- 14707502
TI  - Resurrection of Proteocephalus sagittus (Grimm, 1872) (Cestoda: Proteocephalidea)
      based on morphological and molecular data.
AB  - This paper presents a redescription of the proteocephalidean cestode
      Proteocephalus sagittus (Grimm, 1872) based on freshly collected specimens from
      the type-host, the stone loach Barbatula barbatula (L.) (family Balitoridae),
      from the Czech Republic. This species has recently been synonymised with P.
      torulosus (Batsch, 1786), a parasite of cyprinid fishes in the Holarctic Region,
      but it differs in the following characters: (i) scolex morphology (scolex
      rounded, with more apically situated suckers and lacking longitudinal wrinkles in
      P. sagittus versus large and club-shaped, with more laterally situated suckers
      and longitudinal wrinkles in P. torulosus); (ii) position of the vagina (opens
      anterior to the cirrus-sac in P. sagittus versus overlapping its distal region
      dorsally in P. torulosus); (iii) length of the cirrus-sac (shorter in P.
      sagittus); (iv) osmoregulatory canals (more distinct and situated more laterally,
      but almost indistinguishable and more medial in P. torulosus); and (v) sequences
      of the partial 18S rRNA (V4 region - 96.9% similarity) and 5.8S-ITS2 genes (65.9%
      similarity). P. pamirensis Dzhalilov & Ashurova, 1971, a poorly described species
      from the Tibetan stone loach Noemacheilus stoliczkai[= Tryplophysa stoliczkae
      (Steindachner)] in Tadjikistan, is synonymised with P. sagittus.

PMID- 14707503
TI  - First report of Polygenis (Polygenis) roberti beebei (Fox, 1947) (Siphonaptera:
      Rhopalopsyllidae) in Argentina, with a new host record and morphological data.
AB  - In the present study we report the presence of Polygenis (Polygenis) roberti
      beebei (Fox, 1947) for the first time in Argentina (23 degrees 56'S, 64 degrees
      28'W, Jujuy Province). A new host record (the rodent Oryzomys russatus) and
      morphological details are also presented. Although the Argentinean specimens fit
      descriptions and illustrations given previously, the only studied male differs
      from the specimens collected from other localities in the characteristics of its
      aedeagus. Collections of further material and morphological studies are needed in
      order to analyse the taxonomic status of the specimens from Argentina.

PMID- 14707504
TI  - Clestobothrium neglectum (Lonnberg, 1893) n. comb. (Cestoda: Bothriocephalidae)
      from the tadpole fish Raniceps raninus (L.) (Gadidae) from Sweden.
AB  - Clestobothrium neglectum (Lonnberg, 1893) n. comb. is redescribed from specimens
      previously deposited in The Natural History Museum, London, UK by Dr David I.
      Gibson obtained from the intestine of the tadpole fish Raniceps raninus (Gadidae)
      collected from off the western coast of Sweden, near Kristineberg. C. neglectum
      resembles C. crassiceps (Rudolphi, 1819), the type- and only species currently
      recognised in the genus, but differs in having fine spiniform-like structures
      that are likely microtriches covering the posterior fourth of the scolex and all
      proglottids, a highly folded tegument forming numerous longitudinal ridges on
      both the dorsal and ventral surfaces of the proglottids giving them a scalloped
      appearance, a somewhat smaller egg (68 x 35 vs 75 x 40 microm), a U-shaped rather
      than H-shaped ovary and more testes (70-85 vs 40-50 per proglottid). C. neglectum
      is also compared to two species with similar scoleces that were previously
      assigned to Clestobothrium, Bothriocephalus acheilognathi Yamaguti, 1934 and B.
      kivuensis Baer & Fain, 1958 (considered to be synonymous with B. acheilognathi by
      Pool, 1987). This is the first report of a species of Clestobothrium Luhe, 1899
      (Bothriocephalidae) from a gadid fish.

PMID- 14707505
TI  - Pseudolernentoma brasiliensis n. g., n. sp. (Copepoda: Poecilostomatoida:
      Chondracanthidae) parasitic on Genypterus brasiliensis (Osteichthyes: Ophidiidae)
      from off the State of Rio de Janeiro, Brazil.
AB  - Pseudolernentoma, a new chondracanthid genus was proposed to accommodate
      Pseudolernentoma brasiliensis n. g., n. sp., parasitic on the pink cusk-eel
      Genypterus brasiliensis Regan, from off the coast of Rio de Janeiro, Brazil. The
      new genus can be differentiated from the other genera of the Chondracanthidae by
      the presence of an inflated head with lateral expansions and anteroventral
      bifurcate processes on the trunk.

PMID- 14707506
TI  - Four new species of Cichlidogyrus Paperna, 1960 (Monogenea, Ancyrocephalidae),
      all gill parasites from African mouthbreeder tilapias of the genera Sarotherodon
      and Oreochromis (Pisces, Cichlidae), with a redescription of C. thurstonae
      Ergens, 1981.
AB  - A study of Oreochromis niloticus (Linnaeus), O. aureus (Steindachner),
      Sarotherodon caudomarginatus (Boulenger), S. galilaeus (Linnaeus) and S.
      galilaeus sanagaensis (Thys van den Audenaerde) (Teleostei, Cichlidae) from
      different locations in Africa (Burkina Faso, Cameroon, Guinea, Niger and Senegal)
      revealed the presence of 11 species of monogenean gill parasites. Four, belonging
      to Cichlidogyrus Paperna, 1960 and considered as new species, are described: C.
      rognoni n. sp., C. douellouae n. sp., C. giostrai n. sp. and C. njinei n. sp.
      They are distinguished by the shape and/or size of the sclerotised parts of the
      haptoral and copulatory complexes. C. thurstonae Ergens, 1981 from O. niloticus
      is redescribed.

PMID- 14707507
TI  - Redescription of Diesingia megastoma (Diesing, 1836) Sambon, 1922, a pentastomid
      parasite from the South American terrapin Hydromedusa tectifera Cope.
AB  - Slide-mounted material of the pentastomid parasite Diesingia megastoma (Diesing,
      1836) Sambon, 1922 from the South American chelonian Hydromedusa tectifera Cope
      is reviewed and the perfunctory, often omissive, description of the species is
      amended. The strong morphological similarities between D. megastoma and the
      crocodilian and chelonian pentastome genera of the family Sebekiidae Sambon,
      1922, Alofia Giglioli, 1922, Selfia Riley, 1994, Sebekia Sambon, 1922, Agema
      Riley, Hill & Huchzermeyer, 1997, Leiperia Sambon, 1922 and Pelonia Junker &
      Boomker, 2002, clearly place Diesingia Sambon, 1922 within the same family.
      However, the unique combination of its main diagnostic criteria makes Diesingia a
      distinct genus. The absence of an elaborate, flared cirrus-tip in D. megastoma
      distinguishes it from Leiperia, while emphasizing its similarity to the remaining
      genera mentioned above. D. megastoma resembles Alofia in that it possesses
      smooth, flat-topped hooks and an anteriorly open oral cadre with an oesophageal
      peg. The copulatory spicules of Diesingia, however, lack the double-hooked
      collar, typical for Alofia and Selfia. Unlike the peg-like extension of the
      fulcra of the hooks of Sebekia, that of D. megastoma is cowl-like and carries
      spines only on the anterior fulcra. Moreover, the hooks of Sebekia are usually
      convex and spinose and the ovoid oral cadre is closed anteriorly. Diesingia
      differs from Pelonia through the latter's smooth but dorsally convex and
      extension-free hooks. The copulatory spicules of Pelonia and Agema are
      reminiscent of the basic build found in Sebekia, whereas in D. megastoma the
      short, ventral extension of the cowry shell-shaped base of the copulatory
      spicules has been transformed into a structure resembling the collembolan
      fulcrum. The latter is connected to the base via a joint, a configuration which
      is unique in the Sebekiidae.

PMID- 14707508
TI  - Taxonomic revision of Joyeuxilepis Spassky, 1947 (Cestoda: Amabiliidae):
      redescriptions of J. acanthorhyncha (Wedl, 1855) and J. fuhrmanni (Solomon,
      1932), a key and a new generic diagnosis.
AB  - Two species of Joyeuxilepis Spassky, 1947 with 14 rostellar hooks are
      redescribed: J. acanthorhyncha (Wedl, 1855) on the basis of specimens from
      Tachybaptus ruficollis in Bulgaria and J. fuhrmanni (Solomon, 1932) on the basis
      of the holotype from 'coot' (= ? Podicipedidae) in Kenya. The critical analysis
      of the previous records of J. acanthorhyncha reveals that the host-range of this
      species includes T. ruficollis, Podiceps nigricollis and P. grisegena. The
      reliable diagnostic characters of Joyeuxilepis are re-evaluated. J. biuncinata
      (Joyeux & Baer, 1943), J. acanthorhyncha, J. decacantha (Fuhrmann, 1913), J.
      pilatus Borgarenko & Gulyaev, 1991, J. fuhrmanni, J. uralensis Gulyaev, 1989, J.
      decacanthoides Borgarenko & Gulyaev, 1991, J. octacantha (Rees, 1973), J.
      azerbaijanica (Matevosyan & Sailov, 1963) and J. fimbriata (Borgarenko, Spasskaya
      & Spassky, 1972) are recognised as valid species of Joyeuxilepis. A new generic
      diagnosis for this genus and an identification key to its constituent species are
      presented.

PMID- 14707509
TI  - Description of Paeon asymboli n. sp. (Copepoda: Sphyriidae), parasitic on
      Asymbolus spp. (catsharks) and a new host record for P. australis Kabata, 1993.
AB  - Paeon asymboli n. sp. (Copepoda: Sphyriidae) is described and illustrated from
      two female specimens taken from the gills of a grey spotted catshark Asymbolus
      analis (Ogilby) and an orange spotted catshark A. rubiginosus (Last, Gomon &
      Gledhill) (Scyliorhinidae) from off southeastern Queensland, Australia. The key
      features for identification are: a pear-shaped trunk, longer than it is wide,
      along with a cephalothorax characterised by two large ventral papillae,
      projecting laterally and supporting a number of secondary lobes; a single mid
      line, sub-conical papilla located antero-dorsal to the ventral papillae; an
      anterior surface bearing two prominent stalked papillae; and an absence of
      posterolateral lobular processes. P. australis Kabata, 1993 is recorded for the
      first time from the eastern shovelnose ray Aptychotrema rostrata (Shaw & Nodder)
      (Rhinobatidae).

PMID- 14707510
TI  - Enzyme replacement therapy in heterozygous females with Fabry disease: results of
      a phase IIIB study.
AB  - Fabry disease is an X-linked glycosphingolipid storage disorder caused by a
      deficiency of alpha-galactosidase A. Affected patients experience debilitating
      neuropathic pain and have premature mortality due to renal failure,
      cardiovascular disease or cerebrovascular complications. The disease may be X
      linked dominant, since most females heterozygous for Fabry disease are affected
      clinically. We evaluated the safety, efficacy and pharmacokinetics of agalsidase
      alfa (Replagal) administered intravenously to female patients with Fabry disease
      in an open-label, single-centre study. Fifteen severely affected patients
      received agalsidase alfa at 0.2 mg/kg every other week for up to 55 weeks.
      Agalsidase alfa was safe and well-tolerated in female patients. None of the
      patients developed antibodies or experienced an infusion reaction to agalsidase
      alfa. The pharmacokinetic profile of agalsidase alfa in female patients is
      comparable to the pharmacokinetics of agalsidase alfa in male patients. Mean
      urine sediment and plasma Gb3 levels decreased from baseline at 13, 27 and 41
      weeks. A significant decrease in left ventricular mass from baseline was seen at
      weeks 27 (p = 0.003) and 41 (p = 0.039), and a significant reduction in QRS
      durations was seen at week 27 (p = 0.007). Furthermore, there was a significant
      improvement in quality of life. Renal function did not deteriorate in these 15
      female patients over the 13- to 41-week period of observation. We conclude that
      enzyme replacement therapy with agalsidase alfa was safe and effective in female
      patients heterozygous for Fabry disease.

PMID- 14707511
TI  - A model of neuronopathic Gaucher disease.
AB  - Gaucher disease (GD) is a lysosomal disorder involving the accumulation of
      glucocerebroside in the liver, spleen, bones and brain. Some patients exhibit
      only systemic disease (type I), but others have additional neurological signs
      which may lead to rapid neurodegeneration in infancy (type II) or take a more
      intermediate course (type III). Types II and III are collectively known as
      neuronopathic Gaucher disease (NGD). Systemic disease can now be treated by
      enzyme replacement therapy (ERT), but its efficacy in NGD is limited. Two infants
      who presented with bulbar palsy and failure to thrive were enzymatically
      diagnosed at 8 months with NGD. They were started on high-dose ERT (120 IU/kg
      every 2 weeks). Both underwent serial oculomotor assessment and an audiological
      battery, including visual reinforcement audiometry, otoacoustic emissions, and
      the auditory brain stem response (ABR). Biochemical markers showed an incomplete
      systemic response to ERT, but neurological deterioration was relentless, leading
      to death at 16 and 25 months. Oculomotor testing revealed a complete absence of
      saccadic eye movements and progressive bilateral sixth nerve palsy in one.
      Audiological assessment revealed progressive deterioration of ABRs, but with
      normal peripheral hearing and otoacoustic emissions. Both infants showed
      neurological deterioration in spite of high-dose ERT. The audiological findings
      suggested a loss of inner hair cell pathway function with preserved outer hair
      function, similar to what is seen in auditory neuropathy. The unusual pattern of
      audiological and oculomotor abnormalities is consistent with an excitotoxic
      mechanism predisposing nerve cells to glucocerebroside toxicity. Such excitotoxic
      damage may be amenable to direct therapeutic intervention.

PMID- 14707512
TI  - A neurological symptom survey of patients with type I Gaucher disease.
AB  - Gaucher disease is an inborn error of glycosphingolipid metabolism resulting from
      deficiency of the lysosomal enzyme glucocerebrosidase. The majority of the
      patients (with type I disease) do not have primary central nervous system
      involvement. However, several studies have noted that secondary neurological
      complications may develop as a consequence of nerve root or spinal cord
      compression following vertebral body collapse or, for those with coagulation
      disorders, bleeding within confined compartments. An epidemiological survey was
      conducted to ascertain the incidence of neurological symptoms in patients with
      Gaucher disease type I (GD I). The survey included a review of the patients'
      medical history, an estimate of Gaucher disease severity according to a modified
      Symptom Severity Index (SSI), and completion of a questionnaire regarding their
      neurological status and Quality of Life (QoL) according to the SF-36 Health
      Survey. Seventy-three per cent of respondents were found to have experienced at
      least one neurological complaint in the preceding 3 months. Adult patients with
      Gaucher disease often have other medical problems unrelated to their primary
      diagnosis. Thus, the high incidence of neurological complaints in these patients
      may be attributable to concurrent medical problems and/or side-effects from
      concomitant medications. These issues may influence patients' assessment of their
      disease severity and/or response to treatment.

PMID- 14707513
TI  - Prerequisites and strategies for prenatal diagnosis of respiratory chain
      deficiency in chorionic villi.
AB  - Prenatal diagnosis for respiratory chain deficiencies is a complex procedure that
      requires a thorough diagnostic work-up of the index patient. This includes
      confirmation of the clinical and metabolic evaluations through histological and
      enzymatic examinations of tissue biopsies. Prenatal diagnosis currently relies on
      biochemical assays of respiratory chain complexes in chorionic villi or
      amniocytes and is possible by mutation analysis of nuclear genes in a limited but
      increasing proportion of cases. Based on a recent survey of prenatal diagnosis in
      families with complex I and complex IV deficiencies, performed at Nijmegen Centre
      for Mitochondrial Disorders (NCMD), prerequisites and strategies for performing
      prenatal diagnosis have been developed to increase reliability. Biochemical
      investigations in chorionic villi can be done reliably if the respiratory chain
      enzyme deficiency is expressed in both skeletal muscle and skin fibroblasts to
      rule out tissue specificity. No mitochondrial DNA defects must be suspected or
      established. The NCMD does not offer prenatal diagnosis until all the
      prerequisites have been confirmed. We expect prenatal diagnosis at the molecular
      level to become more feasible in time as the mutational spectrum broadens with
      advances in medical research.

PMID- 14707514
TI  - Respiratory complex II defect in siblings associated with a symptomatic secondary
      block in fatty acid oxidation.
AB  - The mitochondrial oxidative phosphorylation and fatty acid oxidation pathways
      have traditionally been considered independent major sources of cellular energy
      production; however, case reports of patients with specific enzymatic defects in
      either pathway have suggested the potential for a complex interference between
      the two. This study documents a new site of interference between the two
      pathways, a site in respiratory complex II capable of producing clinical signs of
      a block in fatty acid oxidation and reduced in vitro activity of acyl-CoA
      dehydrogenases. The initial patient, and later her newborn sibling, had mildly
      dysmorphic features, lactic acidosis and a defect in mitochondrial respiratory
      complex II associated with many biochemical features of a block in fatty acid
      oxidation. Results of in vitro probing of intact fibroblasts from both patients
      with methyl[2H3]palmitate and L-carnitine revealed greatly increased
      [2H3]butyrylcarnitine; however, the ratio of dehydrogenase activity with butyryl
      CoA with anti-MCAD inactivating antibody (used to reveal SCAD-specific activity)
      to that with octanoyl-CoA was normal, excluding a selective SCAD or MCAD
      deficiency. Respiratory complex II was defective in both patients, with an absent
      thenoyltrifluoroacetone-sensitive succinate Q reductase activity that was
      partially restored by supplementation with duroquinone. Although secondary, the
      block in fatty acid oxidation was a major management problem since attempts to
      provide essential fatty acids precipitated acidotic decompensations. This study
      reinforces the need to pursue broadly the primary genetic defect within these two
      pathways, making full use of increasingly available functional and molecular
      diagnostic tools.

PMID- 14707515
TI  - Biochemical characterization of two mutants of human pyruvate dehydrogenase,
      F205L and T231A of the E1alpha subunit.
AB  - Mutations in the E1alpha subunit of the pyruvate dehydrogenase multienzyme
      complex may result in congenital lactic acidosis, but little is known about the
      consequences of these mutations at the enzymatic level. Here we characterize two
      mutants (F205L and T231A) of human pyruvate dehydrogenase in vitro, using the
      enzyme expressed in Escherichia coli. Wild-type and mutant proteins were purified
      successfully and their kinetic parameters were measured. F205L shows impaired
      binding of the thiamin diphosphate cofactor, which may explain why patients
      carrying this mutation respond to high-dose vitamin B1 therapy. T231A has very
      low activity and a greatly elevated Km for pyruvate, and this combination of
      effects would be expected to result in severe lactic acidosis. The results lead
      to a better understanding of the consequences of these mutations on the
      functional and structural properties of the enzyme, which may lead to improved
      therapies for patients carrying these mutations.

PMID- 14707516
TI  - Efficacy of multidisciplinary approach in the treatment of two cases of
      nonclassical infantile glycogenosis type II.
AB  - Glycogenosis type II (GSD II) is a lysosomal storage disorder due to acid alpha
      glucosidase deficiency. We report the results of a clinical multidisciplinary
      approach in two cases of nonclassical infantile GSD II. The patients received a
      high-protein diet by percutaneous enteral gastrostomy (PEG), mechanical
      ventilatory support by tracheostomy and a physiotherapy programme. After 12
      months of treatment, the patients showed significant improvement in muscular
      strength, nutritional state and respiratory function. Electrocardiography (ECG)
      and echocardiography improved in both patients. They maintained good clinical
      conditions for a period of 18 and 20 months, respectively; thereafter they
      presented with an elevated and persistent fever that was not correlated to a
      septic status and was not responsive to any antipyretic treatment. They
      deteriorated progressively and died. This study shows how a multidisciplinary
      approach may be useful to improve, even if temporarily, the clinical course of
      nonclassical infantile GSD II.

PMID- 14707517
TI  - Phenylalanine can be detected in brain tissue of healthy subjects by 1H magnetic
      resonance spectroscopy.
AB  - Transport of phenylalanine (Phe) and the other large neutral amino acids across
      the blood-brain barrier plays a crucial role in the pathogenesis of
      phenylketonuria (PKU). Thus, investigation of Phe transport kinetics by means of
      proton magnetic resonance spectroscopy (1H MRS) became an important research area
      in the mid 1990s. As 1H MRS measurements of brain phenylalanine are restricted to
      tissue concentrations above 100-150 micromol/kg wet weight, this approach was
      possible only in PKU patients, and comparison with healthy controls was not
      achieved. Using standardized single-dose oral Phe loading in three healthy
      subjects, it was shown that Phe values increase steeply, peak at about 1 h post
      load, and decrease thereafter. In a single case study, repetitive Phe loading was
      then performed to achieve a plateau of high blood Phe concentrations for several
      hours. It was demonstrated that detection and monitoring of brain Phe
      concentrations is feasible by means of 1H MRS. This approach constitutes a
      prerequisite for describing carrier kinetics in health.

PMID- 14707518
TI  - Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical
      and molecular studies.
AB  - From 1989 to 2001, 1,336,145 newborns were screened for biotinidase deficiency in
      Hungary. Fifty-eight children with the disorder were identified as enzyme
      deficient. We have characterized the clinical and biochemical features and
      mutations of 20 of these children. Eleven children had profound biotinidase
      deficiency, 7 had partial biotinidase deficiency, and 2 were found to be
      heterozygous for profound deficiency by mutation analysis. Seventeen different
      mutations were identified in this population including seven novel mutations. Six
      of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C,
      1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five
      Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was
      heterozygous for this mutation. Most of the children with profound deficiency
      have been asymptomatic on therapy; however, four exhibited minimal brain
      abnormalities, motor delay and abnormal blood chemistries. Compliance with
      therapy must be questioned in these cases. Of clinical importance, all of the
      children with partial deficiency exhibited mild symptoms at the time of
      diagnosis, at several weeks to months of age. These symptoms resolved following
      biotin therapy. This is in contrast to the experience in the United States, where
      the children with partial deficiency have been asymptomatic at the time of
      diagnosis. This finding further indicates that children with partial deficiency
      should be treated. The incidence of biotinidase deficiency in Hungary is more
      than twice that observed in a worldwide survey. These results indicate that
      newborn screening in Hungary is effective and warranted.

PMID- 14707519
TI  - Mutations in galactose-1-phosphate uridyltransferase gene in patients with
      idiopathic presenile cataract.
AB  - Impaired activity of the enzyme galactose-1-phosphate uridyltransferase (GALT)
      has been proposed as a risk factor for idiopathic presenile cataract. A study was
      undertaken to determine the prevalence of the three most common mutations in the
      GALT gene (Q188R, K285N and N314D, including its variant Duarte-2) in a group of
      Slovenian patients with idiopathic presenile cataract. GALT activity was
      determined in the erythrocytes of 30 cataract patients. DNA was isolated from
      their blood and analysed for Q188R, K285N and N314D mutations and IVS5-24G>A
      intronic variation by means of polymerase chain reaction and digestion with
      restriction enzymes. The average GALT activity of the cataract group was 19.5+/
      4.9 U/g Hb, which is lower than the normal range (p = 0.034). Frequencies of
      Q188R, K285N, N314D and Duarte-2 alleles in the cataract group were 0.00%, 5.0%,
      11.7% and 3.3%, respectively. Only the frequency of the K285N mutation was
      significantly higher in the patient group than in the control group (p = 0.0244).
      Our results support the reported association of decreased GALT activity with
      idiopathic presenile cataract. Molecular analysis indicates that, in the
      Slovenian population, this association is linked to the K285N mutation, which is
      neonatally benign in heterozygotes.

PMID- 14707520
TI  - 3-methyglutaconic aciduria in a Chinese patient with glycogen storage disease Ib.
AB  - We report elevated urinary excretion of 3-methylglutaconic (3MGC) and 3
      methylglutaric acids (3MGR) in a patient with glycogen storage disease Ib.
      Combined excretion was 10-fold elevated in comparison to control during
      inadequate glucose maintenance, and still elevated following dietary improvement.
      3MGC acid excretion correlated with plasma lactate and glucose. We speculate that
      imbalanced gluconeogenesis and de novo cholesterol synthesis result in
      secondarily increased 3MGC/3MGR production.

PMID- 14707521
TI  - Rhabdomyolysis in glutaric aciduria type I.
AB  - Recurrent rhabdomyolysis has previously been reported in one patient with
      glutaric aciduria type I. We report rhabdomyolysis in a second, unrelated
      patient, suggesting that there may be a specific association with thismetabolic
      disorder.

PMID- 14707522
TI  - Severe phenotype despite high residual glutaryl-CoA dehydrogenase activity: a
      novel mutation in a Turkish patient with glutaric aciduria type I.
AB  - We report the first patient with the homozygous GCDH mutation M263V, displaying a
      high residual activity in fibroblasts of 30%, but presenting with a severe
      clinical phenotype.

PMID- 14707523
TI  - Normalization of low biotinidase activity in a child with biotin deficiency after
      biotin supplementation.
AB  - We report findings in a Japanese boy with severe skin rash attributable to biotin
      deficiency. The patient had an intracranial malformation and developed biotin
      deficiency due to tube feeding with a single formula for over one year. Results
      of urinary organic acid analysis were consistent with multiple carboxylase
      deficiency, and low biotinidase activity was also observed. After biotin
      supplementation, the skin rash improved and biotinidase activity normalized. We
      speculate that biotin is one regulating factor in the biosynthesis of
      biotinidase.

PMID- 14707524
TI  - Tall stature and progressive overweight in mitochondrial encephalopathy.
AB  - We describe two children carrying an inherited T899C mutation in the
      mitochondrial ATPase 6 gene with mild encephalopathy and normal postnatal growth
      followed by tall stature and obesity. No familial tall stature, endocrine anomaly
      or advanced skeletal age were present. Failure to thrive is a characteristic
      finding in most patients with a mitochondrial disease. Our observations suggest
      that children with encephalomyopathy, even in the presence of a significant
      clinical overgrowth, should be screened for a possible defect in oxidative
      phosphorylation.

PMID- 14707526
TI  - Swiss primary care physicians' knowledge, attitudes and perception towards
      genetic testing for hereditary breast cancer.
AB  - PURPOSE: The Swiss Institute for Applied Cancer Research's (SIAK) Network for
      Cancer Predisposition Testing and Counseling was established in 1999. To define
      its role in the care of individuals with inherited cancer predisposition,
      attitudes, knowledge and perception of primary care physicians towards genetic
      counseling and testing for hereditary breast cancer were examined. METHODS: A
      questionnaire was sent to 1391 primary care physicians in private practice in the
      German-speaking Canton of Zurich. RESULTS: 628 (45%) questionnaires were
      returned: 319/778 (41%) general practitioners, 156/367 (43%) internists, 118/218
      (54%) obstetrician-gynecologists and 22/28 (76%) oncologists answered. Socio
      demographic characteristics were: 74% males and 26% females with a mean age of 51
      and a mean number of 14 years in private practice. Fifty-two percent of
      responding physicians approved of genetic susceptibility testing and seventy
      seven percent would recommend it to individuals at risk if asked for it. Of the
      responding physicians, 47% wanted to disclose test results and discuss its
      consequences and 79% wanted to provide long term care and support, whereas only
      36% and 9%, respectively, assigned these tasks to specialized cancer genetics
      services. Eight knowledge questions had to be answered: 290 (46%) gave 0-2
      correct answers, 284 (45%) gave 3-5 and 54 (9%) gave 6-8 correct answers.
      CONCLUSIONS: Our findings demonstrate that the majority of responding primary
      care physicians in the Canton of Zurich approve of genetic testing for hereditary
      breast cancer and want to play a central role in the management of these
      families, but lack the knowledge to do so efficiently. Our findings underline the
      importance of educational programs in cancer genetics.

PMID- 14707528
TI  - Are there socio-economic inequalities in age of resection of colorectal cancer in
      people with HNPCC?
AB  - The relationship between socio-economic status and health has been consistently
      reported and is thought to be causal. Socio-economic inequalities are present in
      the incidence of and mortality from cancer in general, but not in the incidence
      of colorectal cancer in particular. However, there are socio-economic gradients
      in mortality from colorectal cancer. The socio-economic distribution of incidence
      of and mortality from colorectal cancer in individuals with hereditary non
      polyposis colon cancer (Lynch syndrome) is not known. It is possible that
      increased awareness of and access to screening for colorectal cancer amongst this
      group of individuals reduces the socio-economic gradients seen in the population
      as a whole. We investigated the relationship between socio-economic status and
      age of resection of colorectal cancer in a cohort of individuals with hereditary
      non-polyposis colon cancer. More affluent individuals tended to undergo surgical
      resection for colorectal cancers earlier in their lives than less affluent
      individuals. This relationship was bordering on statistical significance. This
      trend probably represents socio-economic variations in access to treatment. In
      addition, age based diagnostic criteria for hereditary non-polyposis colon cancer
      may, inadvertently, accentuate socio-economic inequalities in outcome.

PMID- 14707527
TI  - What motivates interest in attending a familial cancer genetics clinic?
AB  - The motivation of people who seek advice about a family history of cancer was
      explored in a cross sectional study of new cancer referrals to five regional
      cancer genetics centres in England: the PACT (patient and clinical team)
      psychosocial study. One hundred sixty-two people took part. Measures were source
      of referral, estimated and perceived cancer risk, level of cancer worry, and
      personal and family-centred reasons for wanting to be seen in clinic. General
      practitioners referred more people than hospital doctors, and referred a larger
      proportion of people at low genetic risk of developing cancer. More than half of
      the participants had been the first to raise the issue of their family history of
      cancer. Personal motivation for referral is clearly different for those who have
      had a diagnosis of cancer and for those with children, compared to unaffected and
      childless people, and is characterised by altruistic concern for other family
      members rather than a perception of increased personal risk. Men and people from
      ethnic minorities are very significantly under-represented. Understanding
      people's motivation may be useful in targeting genetic counselling for people
      with a family history of cancer.

PMID- 14707529
TI  - Abstracts presented at the Breast Cancer Linkage Consortium (BCLC) and the
      International Collaborative Group on Familial Breast and Ovarian Cancer (ICG
      FBOC) 14th General Meeting at the Centro Nacional de Investigaciones Oncologica
      (CNIO). Madrid, Spain. 2-4 June 2003.

PMID- 14707531
TI  - Perspectives related to the potential use of vaginal microbicides among drug
      involved women: focus groups in three cities in the United States and Puerto
      Rico.
AB  - HIV transmission through heterosexual contact remains the greatest risk factor
      for women globally. Topical microbicides applied intravaginally may offer a
      female-initiated HIV prevention option for many who are unable or unwilling to
      use male condoms or who would want additional protection. This article presents
      results of focus groups in Bridgeport, Connecticut, Providence, Rhode Island, and
      San Juan, Puerto Rico, with women who use crack or heroin or have male partners
      who inject illegal drugs. Participants revealed motivation for and openness to
      using microbicides effective against HIV should they become available. Additional
      lubrication during intercourse was one of several expected positive features of
      microbicides; women saw lubrication as a means of enhancing pleasure and reducing
      condom irritation and breakage while also protecting them from infection.
      Conversely, some women feared that their male partners would interpret excessive
      lubrication as an indication of infection, improper hygiene, or evidence of sex
      with another man. Focus groups also provided insight into how aspects of
      different women's sexual lives, including partner type, might influence the
      issues that would concern them if and when they tried out new microbicidal
      products in the future.

PMID- 14707532
TI  - Why HIV infections have increased among men who have sex with men and what to do
      about it: findings from California focus groups.
AB  - A resurgence of sexual risk taking, STDs, and HIV incidence has been reported
      among men who have sex with men (MSM) in several countries. We asked 113 MSM in
      12 focus groups conducted in five California cities to identify factors leading
      to increased risk taking and assess prevention messages to reduce risk in this
      population. Participants perceived that HIV risk taking has increased because (1)
      HIV is not the threat it once was due to more effective therapies, (2) MSM
      communicate less about HIV, and social support for being safe has decreased, and
      (3) community norms have shifted such that unsafe sex is more acceptable. The
      prevention messages ranked most likely to motivate risk reduction encouraged
      individuals to seek social support from friends. Themes ranked least likely to
      succeed were those that described the negative consequences of HIV or reinforced
      existing safer sex messages.

PMID- 14707533
TI  - Self-perceived responsibility of HIV-seropositive men who have sex with men for
      preventing HIV transmission.
AB  - Relatively little attention has been paid to unique factors that may motivate HIV
      seropositive men who have sex with men (MSM) to prevent HIV transmission. This
      study examines the beliefs of 250 HIV-seropositive MSM about their responsibility
      for protecting sex partners from HIV infection. Participants completed an open
      ended interview about their sexual practices, substance use, and other HIV
      related issues. Seventy percent of participants were men of color. Most
      participants (72%) spontaneously mentioned issues related to responsibility that
      were represented by three themes: (1) personal responsibility for protecting sex
      partners, (2) partners' responsibility for protecting themselves, and (3) mutual
      responsibility. These beliefs were expressed by 63%, 24%, and 12% of respondents,
      respectively. Motivations underlying beliefs about personal responsibility
      included altruism, self-standards, and self-interest. Beliefs about personal
      responsibility were influenced by participant characteristics, partner
      characteristics, disclosure of HIV status, and contextual factors. The findings
      suggest that self-perceived responsibility may be an important factor that
      affects HIV-seropositive MSM's sexual decision making.

PMID- 14707534
TI  - High rates and positive outcomes of HIV-serostatus disclosure to sexual partners:
      reasons for cautious optimism from a voluntary counseling and testing clinic in
      Dar es Salaam, Tanzania.
AB  - The rates, barriers, and outcomes of HIV serostatus disclosure to sexual partners
      are described for 245 female voluntary counseling and testing (VCT) clients in
      Dar es Salaam, Tanzania. VCT clients were surveyed 3 months after HIV testing to
      describe their HIV-serostatus disclosure experiences. Sixty-four percent of HIV
      positive women and 79.5% of HIV-negative women (p = 0.028) reported that they had
      shared HIV test results with their partners. Among women who did not disclose,
      52% reported the reason as fear of their partner's reaction. Both 81.9% of HIV
      negative women and 48.9% of HIV-positive women reported that their partner
      reacted supportively to disclosure (p < 0.001). Less than 5% of women reported
      any negative reactions following disclosure. VCT should continue to be widely
      promoted. However, intervention approaches such as development of screening tools
      and new counseling approaches are important to ensure the safety of women who
      want to safely disclose HIV serostatus to their sexual partners.

PMID- 14707535
TI  - Predictors of HIV sexual risk behaviors in a community sample of injection drug
      using men and women.
AB  - Injection risk practices and unprotected sex between injection drug users (IDUs)
      and their sexual partners are responsible for a high proportion of AIDS cases and
      new HIV infections in the United States. The purpose of this study was to
      investigate the links between drug use behaviors and psychosocial factors with
      high-risk sexual behaviors among male and female IDUs. Understanding the
      determinants of sexual risk practices among drug users can lead to the
      development of more effective programs to prevent sexual HIV and STD
      transmission. This study enrolled a community sample of 101 IDUs (males = 65,
      females = 36), primarily African American and unemployed, who injected drugs and
      had unprotected sex in the past 3 months. The sample was categorized into highest
      sexual risk (multiple partners and intercourse without condoms) and lower sexual
      risk subgroups. Univariate analyses showed that IDUs at highest sexual risk had
      lower sexual risk reduction self-efficacy (p =.01) and were more likely to be
      African American (p =.02). Drug users at highest sexual risk also used
      noninjected cocaine and crack more frequently (p =.05), were less likely to
      inject heroin (p =.04), and tended to more often inject cocaine (p =.05). IDUs at
      highest sexual risk also tended to more often use crack and methamphetamines.
      Logistic regression analyses showed that injecting cocaine or crack, sexual risk
      reduction self-efficacy, and race were independent predictors of sexual risk
      behavior levels. Sexual risk reduction programs for this population are needed,
      with HIV prevention programs tailored to specific IDU risk reduction needs.

PMID- 14707536
TI  - The life priorities of HIV-seropositive injection drug users: findings from a
      community-based sample.
AB  - Using cross-sectional data from an ethnically diverse sample of 161 HIV
      seropositive injection drug users (IDUs), we investigated (1) how HIV-positive
      IDUs rank their life priorities, (2) whether HIV prioritization (defined as
      whether or not ranking HIV as a top priority) is associated with risk behaviors,
      and (3) potential correlates of HIV prioritization. HIV was ranked as the most
      important priority by 37% of the participants. Among those who did not rank HIV
      as the top priority, housing, money, and safety from violence were particularly
      salient priorities. Those who gave the highest priority to HIV were less likely
      to have unprotected vaginal sex with primary partners who were HIV negative or of
      unknown serostatus, were less likely to split drugs with a used syringe, and used
      fewer numbers of injection drugs. HIV prioritization, however, was not associated
      with sex risk behaviors with nonprimary partners and HIV-positive primary
      partners. Significant correlates of HIV prioritization included age and the use
      of a heroin/stimulant mixture. These findings provide a number of important
      implications for HIV prevention intervention research for HIV-positive IDUs.

PMID- 14707537
TI  - The utility of the PRECEDE model in predicting HIV risk behaviors among Puerto
      Rican injection drug users.
AB  - The PRECEDE model for health promotion proposes three types of influences on
      health behaviors: Predisposing, Enabling, and Reinforcing factors. This model was
      used to examine a range of influences on HIV risk behaviors (sharing syringes and
      other injection-related paraphernalia) among Puerto Rican injection drug users
      (IDUs). A total of 698 IDUs were interviewed (438 in East Harlem, New York, and
      260 in Bayamon, Puerto Rico). Both types of risk behaviors were more prevalent in
      Puerto Rico. Similarities in influences on syringe sharing behaviors were found
      in the two sites and included self-efficacy (for reducing injection-related
      sharing) and norms. Influences on the sharing of other injection-related
      paraphernalia were primarily Enabling factors in both communities, and purchasing
      drugs with others was the strongest predictor of paraphernalia sharing. The need
      to address risks associated with joint drug purchasing in both locations and to
      enhance efforts to reduce risks among IDUs in Puerto Rico is indicated.

PMID- 14707538
TI  - Patterns of HIV risk behavior and condom use among youth in Yaounde and Douala,
      Cameroon.
AB  - This study describes the levels of sexual risk behavior and condom use among
      Cameroonian urban youth in order to evaluate the need for reproductive health
      programs targeting youth and to inform the design of such programs. We use data
      from a survey conducted in July-August 2000 among a representative sample of
      1,956 unmarried youth aged 15-24 years. The data show that in urban Cameroon,
      first intercourse often occurs at an early age. Despite the HIV epidemic, a
      substantial fraction of youth, particularly males, continue to have high rates of
      partner change. A substantial fraction of youth consistently use condoms with
      casual partners. However, consistent condom use in regular relationships remains
      low, even though many youth have multiple regular partners. These findings
      illustrate the need for youth-targeted reproductive health programs in urban
      Cameroon. To ensure that youth are reached before they adopt risky behaviors,
      there is a need for programs that target very young teenagers and emphasize
      consistent condom use.

PMID- 14707539
TI  - Factors associated with psychological distress in urban mothers with late-stage
      HIV/AIDS.
AB  - Factors associated with psychological distress were examined in 220 low-income,
      mostly minority mothers with late-stage HIV/AIDS. Mothers lived with at least one
      HIV-negative child of age 2-12 years and participated in a study of the
      effectiveness of a custody planning intervention provided by The Family Center.
      The mothers exhibited extraordinarily high levels of psychological disturbance on
      the Psychiatric Symptom Index (PSI). Multiple regression showed that higher PSI
      Total scores were significantly related to the mother's reports of having non-HIV
      related medical conditions, spending time in bed in the past 2 weeks, having more
      activity restrictions, and having a lot of difficulty caring for her child due to
      ill health. Higher scores also were associated with lower education, experiencing
      more negative life events, and greater receipt and lower adequacy of social
      support. Thus, higher distress was associated with inability to perform usual
      activities and mobilization of support. However, other HIV-related health
      factors, traditional background characteristics, and psychosocial measures (e.g.,
      HIV stigma, parenting stress, family environment) failed to indicate who was most
      vulnerable. Researchers need to identify the mechanisms of risk and develop
      appropriate mental health interventions.

PMID- 14707540
TI  - Dendritic Ih selectively blocks temporal summation of unsynchronized distal
      inputs in CA1 pyramidal neurons.
AB  - The active dendritic conductances shape the input-output properties of many
      principal neurons in different brain regions, and the various ways in which they
      regulate neuronal excitability need to be investigated to better understand their
      functional consequences. Using a realistic model of a hippocampal CA1 pyramidal
      neuron, we show a major role for the hyperpolarization-activated current, Ih, in
      regulating the spike probability of a neuron when independent synaptic inputs are
      activated with different degrees of synchronization and at different distances
      from the soma. The results allowed us to make the experimentally testable
      prediction that the Ih in these neurons is needed to reduce neuronal excitability
      selectively for distal unsynchronized, but not for synchronized, inputs.

PMID- 14707541
TI  - Membrane resonance and stochastic resonance modulate firing patterns of
      thalamocortical neurons.
AB  - We examined the interactions of subthreshold membrane resonance and stochastic
      resonance using whole-cell patch clamp recordings in thalamocortical neurons of
      rat brain slices, as well as with a Hodgkin-Huxley-type mathematical model of
      thalamocortical neurons. The neurons exhibited the subthreshold resonance when
      stimulated with small amplitude sine wave currents of varying frequency, and
      stochastic resonance when noise was added to sine wave inputs. Stochastic
      resonance was manifest as a maximum in signal-to-noise ratio of output response
      to subthreshold periodic input combined with noise. Stochastic resonance in
      conjunction with subthreshold resonance resulted in action potential patterns
      that showed frequency selectivity for periodic inputs. Stochastic resonance was
      maximal near subthreshold resonance frequency and a high noise level was required
      for detection of high frequency signals. We speculate that combined membrane and
      stochastic resonances have physiological utility in coupling synaptic activity to
      preferred firing frequency and in network synchronization under noise.

PMID- 14707542
TI  - Separation of spatio-temporal receptive fields into sums of gaussian components.
AB  - Visual cortical simple cells have been experimentally shown to reveal non-trivial
      spatio-temporal orientation tuning functions comprising different phases of
      specifically tuned enhanced and suppressed activity. A recently developed
      analytical method based on nonlinear neural field models suggests that such space
      time responses should be approximately separable into a sum of temporally
      amplitude modulated Gaussian spatial components. In the present work, we
      investigate this possibility by means of numerical fits of sums of Gaussians to
      response functions observed in experiments and computer simulations. Because the
      theory relates each single component to a particular connectivity kernel between
      the underlying cell classes shaping the response, the relative contribution of
      feedforward and cortex-intrinsical excitatory and inhibitory feedback mechanisms
      to single cell tuning can be approached and quantified in experimental data.

PMID- 14707543
TI  - Configurational and elemental odor mixture perception can arise from local
      inhibition.
AB  - Contrast enhancement via lateral inhibitory circuits is a common mechanism in
      sensory systems. We here employ a computational model to show that, in addition
      to shaping experimentally observed molecular receptive fields in the olfactory
      bulb, functionally lateral inhibitory circuits can also mediate the elemental and
      configurational properties of odor mixture perception. To the extent that odor
      perception can be predicted by slow-timescale neural activation patterns in the
      olfactory bulb, and to the extent that interglomerular inhibitory projections map
      onto a space of odorant similarity, the model shows that these inhibitory
      processes in the olfactory bulb suffice to generate the behaviorally observed
      inverse relationship between two odorants' perceptual similarities and the
      perceptual similarities between either of these same odorants and their binary
      mixture.

PMID- 14707544
TI  - A novel method for the topographic analysis of neural activity reveals formation
      and dissolution of 'Dynamic Cell Assemblies'.
AB  - The study of synchronous oscillations in neural systems is a very active area of
      research. However, cognitive function may depend more crucially upon a dynamic
      alternation between synchronous and desynchronous activity rather than
      synchronous behaviour per se. The principle aim of this study is to develop and
      validate a novel method of quantifying this complex process. The method permits a
      direct mapping of phase synchronous dynamics and desynchronizing bursts in the
      spatial and temporal domains. Two data sets are analyzed: Numeric data from a
      model of a sparsely coupled neural cell assembly and experimental data consisting
      of scalp-recorded EEG from 40 human subjects. In the numeric data, the approach
      enables the demonstration of complex relationships between cluster size and
      temporal duration that cannot be detected with other methods. Dynamic patterns of
      phase-clustering and desynchronization are also demonstrated in the experimental
      data. It is further shown that in a significant proportion of the recordings, the
      pattern of dynamics exhibits nonlinear structure. We argue that this procedure
      provides a 'natural partitioning' of ongoing brain dynamics into topographically
      distinct synchronous epochs which may be integral to the brain's adaptive
      function. In particular, the character of transitions between consecutive
      synchronous epochs may reflect important aspects of information processing and
      cognitive flexibility.

PMID- 14707545
TI  - Neural population structures and consequences for neural coding.
AB  - Researchers studying neural coding have speculated that populations of neurons
      would more effectively represent the stimulus if the neurons "cooperated:" by
      interacting through lateral connections, the neurons would process and represent
      information better than if they functioned independently. We apply our new theory
      of information processing to determine the fidelity limits of simple population
      structures to encode stimulus features. We focus on noncooperative populations,
      which have no lateral connections. We show that they always exhibit positively
      correlated responses and that as population size increases, they perfectly
      represent the information conveyed by their inputs regardless of the individual
      neuron's coding scheme. Cooperative populations, which do have lateral
      connections, can, depending on the nature of the connections, perform better or
      worse than their noncooperative counterparts. We further show that common notions
      of synergy fail to capture the level of cooperation and to reflect the
      information processing properties of populations.

PMID- 14707546
TI  - Profile of adult rat sensory neuron loss, apoptosis and replacement after sciatic
      nerve crush.
AB  - Following permanent transection of the adult rat sciatic nerve, sensory neuron
      apoptosis in the contributing L4 and L5 dorsal root ganglia can be observed for
      at least 6 months afterwards. To establish the profile of any sensory neuron
      apoptosis and loss over time when axonal regeneration is allowed, serial sections
      of L4 and L5 ganglia were examined and the neurons counted using a stereological
      technique 1, 2 and 3 months after crushing the right sciatic nerve at mid-thigh
      level. Our results show that an identical degree of sensory neuron loss and
      apoptosis occurs 1 month after crush as at 1 month after permanent transection.
      However, at 3 months no neurons undergoing apoptosis could be observed and no
      significant loss could be detected in the ipsilateral ganglia when compared to
      unoperated controls. One explanation was a neuronal replacement mechanism, which
      was investigated by administering bromodeoxyuridine to rats for 1 month after
      sciatic nerve transection or crush, prior to detection using immunohistochemistry
      on sections of their ganglia after 2 months. The presence of bromodeoxyuridine in
      the nuclei of occasional cells that would be counted as neurons on the basis of
      size and morphology indicates that a process of apparent neurogenesis may
      underlie the profile of sensory neuron loss after axotomy.

PMID- 14707547
TI  - Endothelial cell influence on dorsal root ganglion cell formation.
AB  - Although endothelial cells are known to produce neutrotrophic factors,
      endothelial cell influence on growth and survival of ganglion cells has not been
      documented. For this reason, a long-term culture technique was modified to obtain
      dorsal root ganglion (DRG) cells. Cells, among them neurons, were released from
      clusters into the medium for more than four weeks. These cells were grown
      together with endothelial cells either (1) in close contact as contiguous co
      culture, or (2) on porous inserts for non-contiguous co-culture, and, finally,
      (3) without endothelial cells for ganglion cell culture. Samples from the
      cultures were stained for the nuclear Ki-67-antigen to detect proliferating
      cells, and for neurofilaments (NF) to verify the presence of DRG cells with and
      without mitotic figures. The contiguous co-culture contained three times as many
      mitotic DRG cells as other culture set ups. Nerve growth factor had no mitotic
      effect on the different DRG cultures, although it supported the growth of
      endothelial cells. It is concluded that a subpopulation of DRG cells is easily
      harvested from long-term DRG cultures. These DRG cells undergo mitosis when in
      direct contact with endothelial cells.

PMID- 14707548
TI  - Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex
      of the rat.
AB  - Increasing evidence shows that the rostral agranular insular cortex (RAIC) is
      important in the modulation of nociception in humans and rats and that dopamine
      and GABA appear to be key neurotransmitters in the function of this cortical
      region. Here we use immunocytochemistry and path tracing to examine the
      relationship between dopamine and GABA related elements in the RAIC of the rat.
      We found that the RAIC has a high density of dopamine fibers that arise
      principally from the ipsilateral ventral tegmental area/substantia nigra (VTA/SN)
      and from a different set of neurons than those that project to the medial
      prefrontal cortex. Within the RAIC, there are close appositions between dopamine
      fibers and GABAergic interneurons. One target of cortical GABA appears to be a
      dense band of GABAB receptor-bearing neurons located in lamina 5 of the RAIC. The
      GABAB receptor-bearing neurons project principally to the amygdala and nucleus
      accumbens with few or no projections to the medial prefrontal cortex, cingulate
      gyrus, the mediodorsal thalamic nucleus or contralateral RAIC. The current
      anatomical data, together with previous behavioral results, suggest that part of
      the dopaminergic modulation of the RAIC occurs through GABAergic interneurons.
      GABA is able to exert specific effects through its action on GABAB receptor
      bearing projection neurons that target a few subcortical limbic structures.
      Through these connections, dopamine innervation of the RAIC is likely to affect
      the motivational and affective dimensions of pain.

PMID- 14707549
TI  - Regulation of c-Jun N-terminal kinase activation in hydrogen peroxide induced
      neurotoxicity.
AB  - C-Jun N-terminal kinase 1 and 2 (JNK1/2) have been shown to be transiently
      activated and involved in neurotoxicity. We searched for possible upstream
      molecules, which are responsible for the regulation of hydrogen peroxide-(H2O2)
      induced JNK1/2 activation and JNK1/2-mediated apoptotic-like cell death in
      cultured rat cortical neurons. The results showed that JNK1/2 activation
      (monitored by anti-diphosphorylated JNK1/2 antibody) was largely prevented by
      elimination of extracellular Ca2+ or blockage of NMDA-receptors (NMDA-R), and was
      weakly but significantly decreased by blockage of L-type voltage-gated calcium
      channel (L-VGCC); furthermore, JNK1/2 activation was largely prevented by
      inhibition of Ca2+/calmodulin-dependent protein kinase-II (CaMKII) and protein
      tyrosine kinases (PTK). We also found that H2O2-induced apoptotic-like cell death
      was partially prevented by elimination of extracellular Ca2+, or by inhibition of
      NMDA-R, L-VGCC, PTK and CaMKII, respectively. The above results suggest that in
      H2O2-induced neurotoxicity, JNK1/2 activation is mainly mediated by NMDA-R and L
      VGCC. Consequently, PTK and CaMKII are critical intermediaries in JNK1/2
      activation and are mainly responsible for JNK1/2-mediated apoptotic-like cell
      death.

PMID- 14707550
TI  - Comparative localization of ADAMs 10 and 15 in human cerebral cortex normal
      aging, Alzheimer disease and Down syndrome.
AB  - Using immunohistochemical techniques we studied the light microscopic
      localization of ADAMs (A Disintegrin And Metalloprotease) 10 and 15 in different
      neocortical areas of the human brain during normal aging, and also in patients
      with Alzheimer disease (AD) and Down syndrome (DS). ADAM 10, a putative alpha
      secretase involved in Notch signaling, was found in neurons of the perinatal
      cortex. During aging there is an increase in intraneuronal staining intensity and
      in the number of cortical nerve cells that contain the enzyme. Furthermore, in AD
      and DS brains ADAM 10 immunoreactivity was associated with diffuse and neuritic
      plaques. ADAM 15 was detected in perinatal cortical pyramidal cells; during aging
      there was also an increase in intracellular staining and the number of stained
      cells per volume (cell density). In AD brains ADAM 15 was seen in a few diffuse
      plaques. Morphometric analysis revealed a significant reduction of ADAM 10 but
      not ADAM 15 immunoreactive neurons in AD brains in comparison to controls. Our
      findings support the idea that ADAM 10 is involved in the pathophysiology of AD
      and DS. ADAM 15 might be linked to AD via interaction with integrin and/or src
      protein tyrosine kinases.

PMID- 14707551
TI  - Expression of regeneration-related molecules in injured and regenerating striatal
      and nigral neurons.
AB  - Peripheral nerve grafts in the neostriatum promote axonal regeneration from
      restricted classes of CNS neuron, principally cells in the substantia nigra pars
      compacta (SNpc) and striatal cholinergic interneurons. We have examined the
      molecular responses of CNS neurons induced to regenerate axons by tibial nerve
      grafting to the neostriatum of adult rats. Brain sections were probed for mRNAs
      for the transcription factor c-jun, and the cell recognition molecule CHL1, or
      immunoreacted for TrkA or p75, 1 day to 29 weeks after grafting (dpo; wpo). In
      unoperated rats, scattered neurons throughout the neostriatum showed weak signals
      for CHL1 mRNA and slightly stronger signals for c-jun mRNA. Cells of similar
      appearance strongly expressed TrkA but possessed little p75. By 1 dpo, many
      neostriatal neurons of various sizes and GFAP + glial cells near the host/graft
      interface had upregulated CHL1 mRNA, c-jun mRNA and p75. Most of the larger (20
      25 microm diameter) CHL1 mRNA+ cells were also TrkA+, indicating that they were
      NGF-sensitive cholinergic interneurons. From two weeks postgrafting, high levels
      of CHL1 and c-jun mRNAs and p75 in the neostriatum were confined to a few
      presumptive cholinergic interneurons; p75+ cells were also TrkA+ and were larger
      than TrkA+ neurons on the contralateral side. Retrograde labelling showed that
      most p75+ and some TrkA+ neurons regenerated axons through the graft. Neurons in
      the SNpc showed a moderate to strong signal for CHL1 mRNA, weaker signal for c
      jun mRNA, and no p75 or TrkA. Some SNpc cells upregulated c-jun mRNA after graft
      implantation, although they did not upregulate CHL1 mRNA, p75 or TrkA. Since
      neostriatal neurons which regenerate axons into grafts express receptors for NGF,
      and grafts mimic the effects of NGF treatment on these cells, sensitivity to
      graft-derived NGF may be a determinant of their high regenerative capacity. The
      finding that c-jun and CHL1 are consistently expressed by CNS neurons induced to
      regenerate their axons strongly supports the idea that these molecules are
      directly involved in axonal regeneration.

PMID- 14707552
TI  - Cell type-specific reduction of beta tubulin isotypes synthesized in the
      developing gerbil organ of Corti.
AB  - There are seven isotypic forms of the microtubule protein beta tubulin in
      mammals, but not all isotypes are synthesized in every cell type. In the adult
      organ of Corti, each of the five major cell types synthesizes a different subset
      of isotypes. Inner hair cells synthesize only betaI and betaII tubulin, while
      outer hair cells make betaI and betaIV tubulin. Only betaII and betaIV tubulin
      are found in inner and outer pillar cells, while betaI, betaII, and betaIV
      tubulin are present in Deiters cells, and betaI, betaII and betaIII tubulin are
      found in organ of Corti dendrites. During post-natal organ of Corti development
      in the gerbil, microtubules are elaborated in an orderly temporal sequence
      beginning with hair cells, followed by pillar cells and Deiters cells. Using beta
      tubulin isotype-specific antibodies, we show that, in the gerbil cochlea, the
      same three isotypes are present in each cell type at birth, and that a cell type
      specific reduction in the isotypes synthesized occurs in hair cells and pillar
      cells at an unusually late stage in development. No beta tubulin isotypes were
      detected in mature afferent dendrites, but we show that this is because few
      microtubules are present in mature dendrites. In addition, we show that primary
      cilia in inner hair cells, a feature of early development, persist much later
      than previously reported. The findings represent the first description of
      developmental cell type-specific reductions in tubulin isotypes in any system.

PMID- 14707554
TI  - Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine
      hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the
      resolution of shock in patients with severe sepsis: results of a randomized,
      double-blind, placebo-controlled multicenter study (study no. 144-002).
AB  - OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase
      inhibitor 546C88 in patients with septic shock. The predefined primary efficacy
      objective was resolution of shock, defined as a mean arterial pressure > or =70
      mm Hg in the absence of both conventional vasopressors and study drug, determined
      at the end of the 72-hr treatment period. DESIGN: Multicentered, randomized,
      placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive
      care units in Europe, North America, and Australia. PATIENTS: A total of 312
      patients with septic shock diagnosed within 24 hr before randomization.
      INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or
      placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional
      vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine.
      Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated
      according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to
      maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any
      concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for
      vasopressors, systemic hemodynamics, indices of organ function and safety
      (including survival up to day 28) were assessed. The median mean arterial
      pressure for both groups was maintained >70 mm Hg. Administration of 546C88 was
      associated with a decrease in cardiac index while stroke index was maintained.
      Resolution of shock at 72 hr was achieved by 40% and 24% of the patients in the
      546C88 and placebo cohorts, respectively (p =.004). There was no evidence that
      treatment with 546C88 had any major adverse effect on pulmonary, hepatic, or
      renal function. Day 28 survival was similar for both groups. CONCLUSIONS: In this
      study, treatment with the nitric oxide synthase inhibitor 546C88 promoted the
      resolution of shock in patients with severe sepsis. This was associated with an
      acceptable overall safety profile.

PMID- 14707555
TI  - Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L
      arginine hydrochloride (546C88) in patients with septic shock: results of a
      randomized, double-blind, placebo-controlled multicenter study (study no. 144
      002).
AB  - OBJECTIVE: To assess the hemodynamic effects of the nitric oxide synthase
      inhibitor 546C88 in patients with septic shock, although this was not a stated
      aim of the protocol. The predefined primary efficacy objective of the protocol
      was resolution of shock determined at the end of a 72-hr treatment period.
      DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study.
      SETTING: Forty-eight intensive care units in Europe, North America, and
      Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within
      24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to
      receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to
      72 hrs. Conventional vasoactive therapy was restricted to norepinephrine,
      dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr
      546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr
      with the objective to maintain mean arterial pressure at 70 mm Hg while
      attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN
      RESULTS: Requirement for vasopressors, systemic and pulmonary hemodynamics,
      indices of oxygen transport, and plasma concentrations of arginine and nitrate
      were assessed over time. The median mean arterial pressure for both groups was
      maintained > or =70 mm Hg. There was an early increase in systemic and pulmonary
      vascular tone and oxygen extraction, whereas both cardiac index and oxygen
      delivery decreased for patients in the 546C88 cohort. Although these parameters
      subsequently returned toward baseline values, the observed differences between
      the treatment groups, except for pulmonary vascular resistance and oxygen
      extraction, persisted throughout the treatment period, despite a reduced
      requirement for vasopressors in the 546C88 cohort. These changes were associated
      with a reduction in plasma nitrate concentrations, which were elevated in both
      groups before the start of therapy. CONCLUSIONS: The nitric oxide synthase
      inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed
      in patients with septic shock. In this study, treatment with 546C88 for up to 72
      hrs was associated with an increase in vascular tone and a reduction in both
      cardiac index and oxygen delivery. The successful maintenance of a target mean
      arterial blood pressure > or =70 mm Hg was achieved with a reduction in the
      requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents
      (i.e., dopamine and norepinephrine). There were no substantive untoward
      consequences accompanying these hemodynamic effects. An international,
      randomized, double-blind, placebo-controlled phase III study has since been
      conducted in patients with septic shock. Recruitment into the study was
      discontinued due to the emergence of increased mortality in the 546C88-treated
      group.

PMID- 14707556
TI  - Multiple-center, randomized, placebo-controlled, double-blind study of the nitric
      oxide synthase inhibitor 546C88: effect on survival in patients with septic
      shock.
AB  - OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase
      inhibitor 546C88 in patients with septic shock. The predefined primary efficacy
      objective was survival at day 28. DESIGN: Multiple-center, randomized, two-stage,
      double-blind, placebo-controlled, safety and efficacy study. SETTING: A total of
      124 intensive care units in Europe, North America, South America, South Africa,
      and Australasia. PATIENTS: A total of 797 patients with septic shock diagnosed
      for <24 hrs. INTERVENTIONS: Patients with septic shock were allocated to receive
      546C88 or placebo (5% dextrose) for up to 7 days (stage 1) or 14 days (stage 2)
      in addition to conventional therapy. Study drug was initiated at 0.05 mL.kg(
      1).hr(-1) (2.5 mg.kg(-1).hr(-1) 546C88) and titrated up to a maximum rate of 0.4
      mL.kg(-1).hr(-1) to maintain mean arterial pressure between 70 and 90 mm Hg while
      attempting to withdraw concurrent vasopressors. MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic variables, organ function data, microbiological data, concomitant
      therapy, and adverse event data were recorded at baseline, throughout treatment,
      and at follow-up. The primary end point was day-28 survival. The trial was
      stopped early after review by the independent data safety monitoring board. Day
      28 mortality was 59% (259/439) in the 546C88 group and 49% (174/358) in the
      placebo group (p <.001). The overall incidence of adverse events was similar in
      both groups, although a higher proportion of the events was considered possibly
      attributable to study drug in the 546C88 group. Most of the events accounting for
      the disparity between the groups were associated with the cardiovascular system
      (e.g., decreased cardiac output, pulmonary hypertension, systemic arterial
      hypertension, heart failure). The causes of death in the study were consistent
      with those expected in patients with septic shock, although there was a higher
      proportion of cardiovascular deaths and a lower incidence of deaths caused by
      multiple organ failure in the 546C88 group. CONCLUSIONS: In this study, the
      nonselective nitric oxide synthase inhibitor 546C88 increased mortality in
      patients with septic shock.

PMID- 14707557
TI  - Effect of a multiple-site intensive care unit telemedicine program on clinical
      and economic outcomes: an alternative paradigm for intensivist staffing.
AB  - OBJECTIVE: To examine whether a supplemental remote intensive care unit (ICU)
      care program, implemented by an integrated delivery network using a commercial
      telemedicine and information technology system, can improve clinical and economic
      performance across multiple ICUs. DESIGN: Before-and-after trial to assess the
      effect of adding the supplemental remote ICU telemedicine program. SETTING: Two
      adult ICUs of a large tertiary care hospital. PATIENTS: A total of 2,140 patients
      receiving ICU care between 1999 and 2001. INTERVENTIONS: The remote care program
      used intensivists and physician extenders to provide supplemental monitoring and
      management of ICU patients for 19 hrs/day (noon to 7 am) from a centralized, off
      site facility (eICU). Supporting software, including electronic data display,
      physician note- and order-writing applications, and a computer-based decision
      support tool, were available both in the ICU and at the remote site. Clinical and
      economic performance during 6 months of the remote intensivist program was
      compared with performance before the intervention. MEASUREMENTS AND MAIN RESULTS:
      Hospital mortality for ICU patients was lower during the period of remote ICU
      care (9.4% vs. 12.9%; relative risk, 0.73; 95% confidence interval [CI], 0.55
      0.95), and ICU length of stay was shorter (3.63 days [95% CI, 3.21-4.04] vs. 4.35
      days [95% CI, 3.93-4.78]). Lower variable costs per case and higher hospital
      revenues (from increased case volumes) generated financial benefits in excess of
      program costs. CONCLUSIONS: The addition of a supplemental, telemedicine-based,
      remote intensivist program was associated with improved clinical outcomes and
      hospital financial performance. The magnitude of the improvements was similar to
      those reported in studies examining the impact of implementing on-site dedicated
      intensivist staffing models; however, factors other than the introduction of off
      site intensivist staffing may have contributed to the observed results, including
      the introduction of computer-based tools and the increased focus on ICU
      performance. Although further studies are needed, the apparent success of this on
      going multiple-site program, implemented with commercially available equipment,
      suggests that telemedicine may provide a means for hospitals to achieve quality
      improvements associated with intensivist care using fewer intensivists.

PMID- 14707558
TI  - The CRIT Study: Anemia and blood transfusion in the critically ill--current
      clinical practice in the United States.
AB  - OBJECTIVE: To quantify the incidence of anemia and red blood cell (RBC)
      transfusion practice in critically ill patients and to examine the relationship
      of anemia and RBC transfusion to clinical outcomes. DESIGN: Prospective, multiple
      center, observational cohort study of intensive care unit (ICU) patients in the
      United States. Enrollment period was from August 2000 to April 2001. Patients
      were enrolled within 48 hrs of ICU admission. Patient follow-up was for 30 days,
      hospital discharge, or death, whichever occurred first. SETTING: A total of 284
      ICUs (medical, surgical, or medical-surgical) in 213 hospitals participated in
      the study. PATIENTS: A total of 4,892 patients were enrolled in the study.
      MEASUREMENTS AND MAIN RESULTS: The mean hemoglobin level at baseline was 11.0 +/-
      2.4 g/dL. Hemoglobin level decreased throughout the duration of the study.
      Overall, 44% of patients received one or more RBC units while in the ICU (mean,
      4.6 +/- 4.9 units). The mean pretransfusion hemoglobin was 8.6 +/- 1.7 g/dL. The
      mean time to first ICU transfusion was 2.3 +/- 3.7 days. More RBC transfusions
      were given in study week 1; however, in subsequent weeks, subjects received one
      to two RBC units per week while in the ICU. The number of RBC transfusions a
      patient received during the study was independently associated with longer ICU
      and hospital lengths of stay and an increase in mortality. Patients who received
      transfusions also had more total complications and were more likely to experience
      a complication. Baseline hemoglobin was related to the number of RBC
      transfusions, but it was not an independent predictor of length of stay or
      mortality. However, a nadir hemoglobin level of <9 g/dL was a predictor of
      increased mortality and length of stay. CONCLUSIONS: Anemia is common in the
      critically ill and results in a large number of RBC transfusions. Transfusion
      practice has changed little during the past decade. The number of RBC units
      transfused is an independent predictor of worse clinical outcome.

PMID- 14707559
TI  - Effect of an intensive care unit rotating empiric antibiotic schedule on the
      development of hospital-acquired infections on the non-intensive care unit ward.
AB  - OBJECTIVE: We have previously shown that a rotating empirical antibiotic schedule
      could reduce infectious mortality in an intensive care unit (ICU). We
      hypothesized that this intervention would decrease infectious complications in
      the non-ICU ward to which these patients were transferred. DESIGN: Prospective
      cohort study. SETTING: An ICU and the ward to which the ICU patients were
      transferred at a university medical center. PATIENTS: All patients treated on the
      general, transplant, or trauma surgery services who developed hospital-acquired
      infection while on the non-ICU wards. INTERVENTIONS: A 2-yr study consisting of 1
      yr non-protocol-driven antibiotic use and 1-yr quarterly rotating empirical
      antibiotic assignment for patients treated in the ICU from which a portion of the
      patients were transferred. MEASUREMENTS AND MAIN RESULTS: There were 2,088
      admissions to the non-ICU wards during the nonrotation year and 2,183 during the
      ICU rotation year. Of these patients, 407 hospital-acquired infections were
      treated during the nonrotation year and 213 were treated during the ICU rotation
      (19.7 vs. 9.8 infections/100 admissions, p <.0001). During the ICU rotation year
      a decrease in the rate of resistant Gram-positive and resistant Gram-negative
      infections on the non-ICU wards occurred (2.5 vs. 1.6 infections/100 admissions,
      p =.04; 1.0 vs. 0.4 infections/100 admissions, p =.03). Subgroup analysis
      revealed that the decrease in resistant infections on the wards was due to a
      reduction in resistant Gram-positive and resistant Gram-negative infections among
      non-ICU ward patients admitted initially from areas other than the ICU
      implementing the antibiotic rotation (e.g., home, other ward, or a different ICU)
      (1.8 vs. 0.5 infections/100 admissions, p =.0001; 0.7 vs. 0.2 infections/100
      admissions, p =.02), not due to differences for those transferred to the ward
      from the rotation ICU (10.4 vs. 9.7 infections/100 admissions, p = 1.0; 4.3 vs.
      1.9 infections/100 admissions, p =.3). No differences in infection-related
      mortality were detected. CONCLUSIONS: An effective rotating empirical antibiotic
      schedule in an ICU is associated with a reduction in infectious morbidity
      (hospital-acquired and resistant hospital-acquired infection rates) on the non
      ICU wards to which patients are transferred.

PMID- 14707560
TI  - Long-term mortality and quality of life after prolonged mechanical ventilation.
AB  - OBJECTIVE: To describe and identify factors associated with mortality rate and
      quality of life 1 yr after prolonged mechanical ventilation. DESIGN: Prospective,
      observational cohort study with patient recruitment over 26 months and follow-up
      for 1 yr. SETTING: Intensive care units at a tertiary care university hospital.
      PATIENTS: Adult patients receiving prolonged mechanical ventilation.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured mortality rate
      and functional status, defined as the inability to perform instrumental
      activities of daily living (IADLs) 1 yr following prolonged mechanical
      ventilation. The study enrolled 817 patients. Their median age was 65 yrs, 46%
      were women, and 44% were alive at 1 yr. Median ages at baseline of 1-yr survivors
      and nonsurvivors were 53 and 71 yrs, respectively. At the time of admission to
      the hospital, survivors had fewer comorbidities, lower severity of illness score,
      and less dependence compared with nonsurvivors. Severity of illness on admission
      to the intensive care unit and prehospitalization functional status had a
      significant association with short-term mortality rate, whereas age and
      comorbidities were related to long-term mortality. Fifty-seven percent of the
      surviving patients needed caregiver assistance at 1 yr of follow-up. The odds of
      having IADL dependence at 1-yr among survivors was greater in older patients
      (odds ratio 1.04 for 1-yr increase in age) and those with IADL dependence before
      hospitalization (odds ratio 2.27). CONCLUSIONS: Mortality rate after prolonged
      mechanical ventilation is high. Long-term mortality rate is associated with older
      age and poor prehospitalization functional status. Many survivors needed
      assistance after discharge from the hospital, and more than half still required
      caregiver assistance at 1 yr. Interventions providing support for caregivers and
      patients may improve the functional status and quality of life of both groups and
      thus need to be evaluated.

PMID- 14707561
TI  - Using population death rate to predict rate of admissions to the intensive care
      unit.
AB  - OBJECTIVE: To determine whether the intensive care unit (ICU) admission rates of
      new health plan members can be predicted by the mortality of non-ICU-treated
      members. DESIGN: Retrospective study of health records. PATIENTS: Five sequential
      cohorts of new health plan members (298,974 members) seen at any of three
      tertiary care medical centers of a health maintenance organization in northern
      California who joined the health plan during the first quarter of 1994, 1995,
      1996, 1997, or 1998 and retained membership for > or =1 yr. SETTING: Three
      medical centers in northern California. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: We measured rates of ICU admission, death, and mechanical
      ventilation among cohort members. ICU admission rate varied between hospitals and
      over time but was predicted by non-ICU mortality-ICU admission rate = 0.83 x non
      ICU mortality-and was linear throughout its range. In no hospital or time period
      was a higher mortality associated with fewer ICU admissions. Seventeen percent of
      population deaths occurred among ICU patients and did not differ among medical
      centers. CONCLUSIONS: A single linear equation predicted ICU admission rate from
      death rate of non-ICU-treated patients among cohorts of new members. ICU
      admission rates can be predicted from a measure of population illness burden,
      such as the mortality of non-ICU-treated patients. It may be possible to extend
      this analysis to other hospitals and health care systems to evaluate the adequacy
      of ICU services provided.

PMID- 14707562
TI  - Expression and regulation of vascular cell adhesion molecule-1 in human umbilical
      vein endothelial cells induced by sera from severely burned patients.
AB  - OBJECTIVE: The purpose of this study was to determine the expression and
      regulation of vascular cell adhesion molecule (VCAM)-1 in human umbilical vein
      endothelial cells (HUVECs) induced by sera from severely burned patients. DESIGN:
      Controlled laboratory study. SETTINGS: Research laboratory in a university
      hospital. SUBJECTS: HUVECs. INTERVENTIONS: HUVECs were incubated with serum from
      eight healthy controls and eight patients with thermal injuries of >50% total
      body surface area. The experiment was repeated after pretreatment with
      pyrrolidine dithiocarbamate, an inhibitory effect on nuclear factor-kappaB
      activation, SB203580, a specific p38 mitogen-activated protein kinase inhibitor,
      and PD98059, a mitogen-activated protein/extracellular signal-regulated kinase
      inhibitor. MEASUREMENTS AND MAIN RESULTS: Protein and messenger RNA expression of
      VCAM-1 was measured by flow cytometry and reverse transcription-polymerase chain
      reaction respectively. Soluble VCAM-1 level in HUVECs culture supernatants was
      measured by enzyme-linked immunosorbent assay. Sera from severely burned patients
      showed a stimulatory effect on VCAM-1 messenger RNA levels and an increased VCAM
      1 expression on the endothelial cell surfaces. The soluble form of VCAM-1
      molecules was also elevated by the stimulation of burn sera. In vitro peripheral
      blood mononuclear leukocytes adherence to HUVECs incubated with burn sera was
      significantly increased compared with those incubated with control sera. Finally,
      these events were significantly inhibited by pretreatment with antioxidants
      pyrrolidine dithiocarbamate or SB203580, whereas PD98059 had no significant
      effect. CONCLUSIONS: These findings suggest that sera from severely burned
      patients induced up-regulation of VCAM-1 expressions in HUVECs, and this process
      might be largely dependent on oxidant-mediated nuclear factor-kappaB activation
      and p38 mitogen-activated protein kinase pathways.

PMID- 14707563
TI  - Evaluation of density area in dorsal lung region during prone position using
      transesophageal echocardiography.
AB  - OBJECTIVE: To evaluate the changes of density area in the dorsal lung regions of
      acute respiratory distress syndrome patients during prone position using
      transesophageal echocardiography. DESIGN: Retrospective clinical study. SETTING:
      General intensive care unit in a university hospital. PATIENTS: Ten patients with
      acute respiratory distress syndrome who underwent prone position therapy.
      INTERVENTIONS: Density areas in the left dorsal lung region were observed using
      transesophageal echocardiography before and after patients were in the prone
      position for 2 hrs. In five patients, a pediatric transesophageal
      echocardiography probe was left in the esophagus and used for observation during
      the prone procedure. MEASUREMENTS AND MAIN RESULTS: Changes of density area and
      PaO2/FiO2 were observed. The density areas decreased after prone position
      compared with those of preprone position (preprone 11.4 +/- 5.1 cm2, after prone
      5.6 +/- 3.5 cm2, mean +/- sd, p <.01, respectively). There was also a significant
      correlation between the percentage change of density area and PaO2/FiO2 (r =.47,
      p <.05) after prone position. During prone position, the density area decreased;
      however, there was no correlation between the percent changes of density area and
      PaO2/FiO2. CONCLUSION: It was possible to observe the change in density area
      during prone position using transesophageal echocardiography. The change of
      density area estimated with transesophageal echocardiography during prone
      position was useful to estimate the effectiveness of the procedure.

PMID- 14707564
TI  - Aspiration pneumonitis in an overdose population: frequency, predictors, and
      outcomes.
AB  - OBJECTIVE: To characterize the frequency of aspiration pneumonitis in an
      unselected population of overdose patients and, further, to identify factors that
      predispose to aspiration pneumonitis and the outcomes of patients with aspiration
      pneumonitis compared with those without. DESIGN: Retrospective cohort study.
      SETTING: Toxicology unit of a tertiary referral hospital. PATIENTS: All poisoning
      admissions. MEASUREMENTS AND MAIN RESULTS: A total of 71 of 4,562 poisoning
      admissions to the Hunter Area Toxicology Service between January 1997 and October
      2002 had definite aspiration pneumonitis (1.6%; 95% confidence interval, 1.2
      2.0). Older age, Glasgow Coma Score of <15, spontaneous emesis, seizures, delayed
      presentation to hospital, and ingestion of tricyclic antidepressants were
      associated with an increased risk of aspiration pneumonitis. Paracetamol
      poisoning and female sex were associated with a decreased risk of aspiration
      pneumonitis with univariate analysis. Ingestion of alcohol, benzodiazepines,
      antipsychotics, and administration of activated charcoal were not associated with
      aspiration pneumonitis. A logistic regression model for predicting aspiration
      pneumonitis contained seven predictors: age, sex, Glasgow Coma Score of <15 (odds
      ratio, 3.14; 95% confidence interval, 1.87-5.27), emesis (odds ratio, 4.17; 95%
      confidence interval, 2.44-7.13), seizure, tricyclic antidepressant ingestion, and
      time from ingestion to presentation (delay of >24 hrs [odds ratio, 4.42; 95%
      confidence interval, 2.42-8.10]). The mortality for patients with aspiration
      pneumonitis was 8.5% compared with 0.4% for those without (odds ratio, 23; 95%
      confidence interval, 9-60; p <.0001), and they had a significantly higher
      intensive care unit admission rate. The median length of stay of patients with
      aspiration pneumonitis was 126 hrs (interquartile range, 62-210 hrs) compared
      with 14.7 hrs (interquartile range, 7-23 hrs) in patients without (p <.0001).
      CONCLUSIONS: Our study has shown a number of risk factors in overdose patients
      that are associated with aspiration pneumonitis that may allow the early
      identification of these patients for appropriate observation and management.
      Patients with aspiration pneumonitis have a significantly increased mortality and
      length of stay in the hospital.

PMID- 14707565
TI  - Early enteral nutrition in mechanically ventilated patients in the prone
      position.
AB  - OBJECTIVE: To assess the tolerance of early enteral nutrition in critically ill
      patients receiving invasive mechanical ventilation in the prone position. DESIGN:
      Prospective, comparative study. SETTING: General intensive care unit in a
      university-affiliated hospital. PATIENTS: A total of 71 consecutive patients
      receiving invasive mechanical ventilation with early nasogastric enteral
      nutrition were studied for 5 days while being treated continuously in the supine
      position (supine position group, n = 37) or with intermittent prone positioning
      for severe hypoxemia (prone position group, n = 34). INTERVENTIONS: Inclusion
      occurred within 24 hrs of mechanical ventilation initiation. Daily 18-hr enteral
      nutrition via a 14F gastric tube was initiated. Prone position patients were
      turned every 6 hrs as long as PaO2/FiO2 remained at <150, with a FiO2 of 0.6 and
      positive end-expiratory pressure of 10; the head was slightly elevated. When
      supine, patients in both groups were semirecumbent. Residual gastric volume was
      measured every 6 hrs, and enteral nutrition was discontinued if it exceeded 250
      mL or vomiting occurred. MEASUREMENTS AND MAIN RESULTS: The groups were similar
      for age, sex, Simplified Acute Physiology Score II, mortality, and risk factors
      for enteral nutrition intolerance. At baseline, PaO2/FiO2 was lower in prone
      position patients than in supine position patients (127 +/- 55 vs. 228 +/- 102; p
      <.001). As compared with supine position patients, prone position patients had
      significantly greater residual gastric volumes on days 1, 2, and 4 and
      experienced more vomiting episodes (median, 1 [interquartile range, 0-2] vs. 0
      [interquartile range, 0-1]; p <.05). Enteral nutrition was stopped in 82% of
      prone position patients and 49% of supine position patients (p <.01) so that
      daily enteral nutrition volumes were lower with prone position patients. In the
      prone position group, vomiting occurred more frequently in the prone than in the
      supine position (relative risk, 2.5; 95% confidence interval, 1.5-4.0; p <.001).
      CONCLUSION: In critically ill patients receiving invasive mechanical ventilation
      in the prone position, early enteral nutrition is poorly tolerated. Prokinetic
      agents or transpyloric feeding and semirecumbency should be considered to enhance
      gastric emptying and to prevent vomiting in patients receiving mechanical
      ventilation in the prone position.

PMID- 14707566
TI  - Complicated acute myocardial infarction requiring mechanical ventilation in the
      intensive care unit: prognostic factors of clinical outcome in a series of 157
      patients.
AB  - OBJECTIVE: To determine prognostic factors associated with death in patients with
      complicated acute myocardial infarction requiring mechanical ventilation. DESIGN:
      Retrospective chart-based analysis. SETTING: A 22-bed medical intensive care unit
      in a university hospital. PATIENTS: A total of 157 consecutive patients with
      acute myocardial infarction requiring endotracheal intubation and mechanical
      ventilation admitted to an intensive care unit during a 6-yr period.
      INTERVENTIONS: Coronary reperfusion strategy within 12 hrs following symptom
      onset. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics at admission of
      survivors (n = 77) and nonsurvivors (n = 80) were similar regarding demographics,
      medical history, and Glasgow Coma Scale score. Twenty-eight-day intensive care
      unit mortality rate was 51%. The following criteria were higher for nonsurvivors:
      Simplified Acute Severity Score II, 79 +/- 18 vs. 64 +/- 17 (p <.0001); Acute
      Physiology and Chronic Health Evaluation (APACHE) II, 33 +/- 13 vs. 25 +/- 6 (p
      <.0001); incidence of cardiogenic shock (p =.0085) and failing organs (p <.0001);
      coronary artery disease extension (p =.045); and delay between symptom onset and
      coronary reperfusion (p =.0348). Nonsurvivors also had higher serum urea and
      creatinine and lower urine output, arterial pH, and left ventricular ejection
      fraction (p <.05). Mortality rate was higher in patients with PaO2/FiO2 ratio
      <200 than in patients with PaO2/FiO2 ratio >200 at admission (log-rank, 5.016; p
      =.0251). By multivariate analysis, only three factors were independently
      associated with death: APACHE II >29 (odds ratio, 1.132; 95% confidence interval,
      1.013-1.265, p =.0287), serum creatinine >180 micromol/L (odds ratio, 6.151; 95%
      confidence interval, 1.446-26.166, p =.0139), and initial left ventricular
      ejection fraction <0.4 (odds ratio, 1.121; 95% confidence interval, 1.049-1.347,
      p =.0316). Overall, good discrimination was achieved for the risk score model (c
      index, 0.852). CONCLUSIONS: We confirmed the high mortality rate of patients
      admitted to an intensive care unit with acute myocardial infarction requiring
      mechanical ventilation. In these patients, the main risk factors for death found,
      namely high APACHE II, early development of acute renal failure, and low resting
      left ventricular function, reflected the severity of the myocardial infarction.

PMID- 14707567
TI  - Current opinions regarding the importance, diagnosis, and management of delirium
      in the intensive care unit: a survey of 912 healthcare professionals.
AB  - OBJECTIVE: Recently published clinical practice guidelines of the Society of
      Critical Care Medicine recommend monitoring for the presence of delirium in all
      mechanically ventilated patients because of the potential for adverse outcomes
      associated with this comorbidity, yet little is known about healthcare
      professionals' opinions regarding intensive care unit delirium or how they manage
      this organ dysfunction. The aim of this survey was to assess the medical
      community's beliefs and practices regarding delirium in the intensive care unit.
      DESIGN: Survey administration was conducted both without a delirium definition
      (phase 1) and then with a definition of delirium (phase 2). SETTING: Critical
      care meetings and continuing medical education/board review courses from October
      2001 to July 2002. PARTICIPANTS: A convenience sample of physicians (n = 753),
      nurses (n = 113), pharmacists (n = 13), physician assistants (n = 12),
      respiratory care practitioners (n = 8), and others (n = 13). INTERVENTIONS:
      Survey. MEASUREMENTS AND MAIN RESULTS: Participants completed 912 of the surveys.
      The majority (68%) of respondents thought that >25% of adult mechanically
      ventilated patients experience delirium. Delirium was considered a significant or
      very serious problem in the intensive care unit by 92% of healthcare
      professionals, yet underdiagnosis was acknowledged by 78%. Only 40% reported
      routinely screening for delirium, and only 16% indicated using a specific tool
      for delirium assessment. Delirium was considered important in the outcome of
      elderly and young patients by 89% and 60% of the respondents, respectively (p
      <.0001). The most serious complications these professionals associated with
      delirium were prolonged mechanical ventilation, self-injury, and respiratory
      difficulties. Delirium was treated with haloperidol by 66% of the respondents,
      with lorazepam by 12%, and with atypical antipsychotics by <5%. More than 55%
      administered haloperidol and lorazepam at daily doses of < or =10 mg, but some
      used >50 mg/day of either medication. CONCLUSIONS: Most healthcare professionals
      consider delirium in the intensive care unit a common and serious problem,
      although few actually monitor for this condition and most admit that it is
      underdiagnosed. Data from this survey point to a disconnect between the perceived
      significance of delirium in the intensive care unit and current practices of
      monitoring and treatment.

PMID- 14707568
TI  - Effect of neuromuscular blocking agents on gas exchange in patients presenting
      with acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the effects of a 48-hr neuromuscular blocking agents
      (NMBA) infusion on gas exchange over a 120-hr time period in patients with acute
      respiratory distress syndrome. DESIGN: Multiple center, prospective, controlled,
      and randomized trial. SETTING: Four adult medical or mixed medical-surgical
      intensive care units. PATIENTS: A total of 56 patients with acute respiratory
      distress syndrome with a PaO2/FiO2 ratio of <150 at a positive end-expiratory
      pressure of > or =5 cm H2O. INTERVENTIONS: After randomization, patients received
      either conventional therapy without NMBA (control group) or conventional therapy
      plus NMBA for the next 48 hrs. The initial ventilator mode was volume
      assist/control. The ventilator remained on assist-control mode throughout the
      initial 48-hr period in both groups. Tidal volume was 6-8 mL/kg ideal body
      weight. MEASUREMENTS AND MAIN RESULTS: When analyzed for the entire 120 hrs,
      there was a significant effect of the NMBA on the course of PaO2/FiO2 ratio (p
      =.021). Separate comparisons at each time point indicated that patients
      randomized to the NMBA group had a higher PaO2/FiO2 at 48, 96, and 120 hrs after
      randomization. Moreover, a decrease of positive end-expiratory pressure (p =.036)
      was only found in the NMBA group. Two-way repeated-measures analysis of variance
      exhibited a decrease in positive end-expiratory pressure over time (p =.036).
      Concerning short-term effects, there was no modification of PaO2/FiO2 ratio 1 hr
      after randomization in either group. Only one patient (from the control group)
      developed pneumothorax. CONCLUSIONS: Use of NMBA during a 48-hr period in
      patients with acute respiratory distress syndrome is associated with a sustained
      improvement in oxygenation.

PMID- 14707569
TI  - Endotracheal tube intraluminal volume loss among mechanically ventilated
      patients.
AB  - OBJECTIVE: To measure endotracheal tube intraluminal volume loss among
      mechanically ventilated patients. DESIGN: Prospective observational study.
      SETTING: Medical intensive care unit (19 beds) of an urban university-affiliated
      teaching hospital. PATIENTS: A total of 101 patients with acute respiratory
      failure requiring >24 hrs of mechanical ventilation. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Acoustic reflectometry was employed to measure the
      intraluminal volume of 13-cm endotracheal tube segments. The endotracheal tube
      segment volumes were statistically smaller among endotracheal tubes used in
      patients compared with unused endotracheal tubes (5.4 +/- 0.7 vs. 6.0 +/- 0.6 mL,
      p <.001). The average percentage difference in endotracheal tube segment volumes,
      between the unused endotracheal tubes and the endotracheal tubes used in
      patients, was 9.8% (range, 0-45.5%). The percentage difference in the
      endotracheal tube segment volumes increased significantly with increasing
      duration of tracheal intubation (r2 =.766, p <.001). The minimum diameter of the
      endotracheal tube segments was also statistically smaller among endotracheal
      tubes used in patients compared with the unused endotracheal tubes (7.5 +/- 0.4
      vs. 6.7 +/- 1.2 mm, p <.001). CONCLUSIONS: Endotracheal tube intraluminal volume
      loss is common among patients with acute respiratory failure requiring mechanical
      ventilation and increases with prolonged tracheal intubation.

PMID- 14707570
TI  - Oral decontamination is cost-saving in the prevention of ventilator-associated
      pneumonia in intensive care units.
AB  - OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is
      assumed to increase costs of intensive care unit stay, it is unknown whether
      prevention of VAP by means of oropharyngeal decontamination is cost-effective.
      Because of wide ranges of individual patient costs, crude cost comparisons did
      not show significant cost reductions. DESIGN: Based on actual cost data of 181
      individual patients included in a former randomized clinical trial, cost
      effectiveness of prevention of VAP was determined using a decision model and
      univariate sensitivity analyses, and bootstrapping was used to assess the impact
      of variability in the various outcomes. DATA SOURCE: Published data on prevention
      of VAP by oropharyngeal decontamination, which resulted in a relative risk for
      VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean
      costs of the intervention were 351 dollars per patient (32 dollars per patient
      per day). All other costs were derived from the hospital administrative database
      for all individual patients. RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led
      to mean total costs of 16,119 dollars and 18,268 dollars for patients without
      preventive measures administered. Thus, costs were saved and instances of VAP
      were prevented. Similar results were observed in terms of overall survival.
      RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the
      relative risk for VAP because of intervention is <0.923, the costs of the
      intervention are less than 2,500 dollars, and the prevalence of VAP without
      intervention is >4%. Bootstrapping confirmed that, with about 80% certainty,
      oropharyngeal decontamination results in prevention of VAP and simultaneously
      saves costs. In terms of a survival benefit, the results are less evident; the
      results indicate that with only about 60% certainty can we confirm that
      oropharyngeal decontamination would result in a survival benefit and
      simultaneously save costs. CONCLUSIONS: This study provides strong evidence that
      prevention of VAP by means of oropharyngeal decontamination is cost-effective.

PMID- 14707571
TI  - Urinary S100B protein measurements: A tool for the early identification of
      hypoxic-ischemic encephalopathy in asphyxiated full-term infants.
AB  - OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of
      perinatal mortality and morbidity. To date, there are no reliable methods to
      detect which infants will develop brain damage after asphyxia insult. DESIGN AND
      SETTING: Prospective study conducted in three tertiary departments of neonatology
      from December 1999 to July 2002. PARTICIPANTS: A total of 44 infants with
      perinatal asphyxia and 68 control infants. INTERVENTION: Routine laboratory
      variables, neurologic patterns, ultrasound imaging, and urine concentrations of
      S100B protein were determined at nine time points. MAIN OUTCOME MEASURES: The
      concentrations of S100B protein in urine were measured using an
      immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, and 72
      hrs after birth. The results were correlated with the presence or absence of
      hypoxic-ischemic encephalopathy. Routine laboratory parameters and neurologic
      patterns were assessed at the same time as urine sampling. RESULTS: S100B protein
      levels were significantly higher in samples collected at all monitoring time
      points from newborns with perinatal asphyxia with or without hypoxic-ischemic
      encephalopathy than in samples from normal infants (all p <.001). When
      asphyxiated infants were subdivided according to the presence of mild or absence
      of hypoxic-ischemic encephalopathy (group A) and of moderate or severe hypoxic
      ischemic encephalopathy (group B), S100B levels were significantly higher at all
      the predetermined monitoring time points in group B infants than group A or
      control infants (all p <.001). An S100B concentration cutoff of 0.41 microg/L at
      first urination had a sensitivity of 91.3% and a specificity of 94.6% for
      predicting the development of hypoxic-ischemic encephalopathy. The sensitivity
      and specificity of measurements obtained from 4 to 72 hrs after birth were up to
      100% and 98.8%, respectively. CONCLUSIONS: Longitudinal S100B protein
      measurements in urine soon after birth are a useful tool to identify which
      asphyxiated infants are at risk of hypoxic-ischemic encephalopathy and its
      possible neurologic sequelae.

PMID- 14707572
TI  - Linezolid for treatment of ventilator-associated pneumonia: a cost-effective
      alternative to vancomycin.
AB  - OBJECTIVES: To determine the incremental cost-effectiveness of linezolid compared
      with vancomycin for treatment of ventilator-associated pneumonia due to
      Staphylococcus aureus. DESIGN: Decision model analysis of the cost and efficacy
      of linezolid vs. vancomycin for treatment of ventilator-associated pneumonia. The
      primary outcome was the incremental cost-effectiveness of linezolid in terms of
      cost per added quality-adjusted life-year gained. Other outcomes were the
      marginal costs per hospital survivor and per year of life saved generated by
      using linezolid. Model estimates were derived from prospective trials of
      linezolid for ventilator-associated pneumonia and from other studies describing
      the costs and outcomes for ventilator-associated pneumonia. SETTING AND PATIENTS:
      Hypothetical cohort of 1,000 patients diagnosed with ventilator-associated
      pneumonia. INTERVENTIONS: In the model, patients received either linezolid or
      vancomycin. MEASUREMENTS AND MAIN RESULTS: The incremental cost-effectiveness of
      linezolid was calculated as the additional quality-adjusted life-years resulting
      from therapy with linezolid divided by the sum of the incremental costs arising
      because of use of linezolid (e.g., higher direct costs for linezolid, costs per
      in-hospital care of survivors, and posthospitalization costs). Despite its higher
      cost, linezolid was cost-effective for treatment of ventilator-associated
      pneumonia. The cost per quality-adjusted life-year equals approximately 30,000
      dollars. The model was moderately sensitive to the estimated efficacy of
      linezolid over vancomycin. Nonetheless, even with all inputs simultaneously
      skewed against, linezolid remains a cost-effective option (cost per quality
      adjusted life-year approximately 100,000 dollars). Based on Monte Carlo
      simulation, the results of our analysis are robust across a range of model inputs
      and assumptions (95% confidence interval for cost per quality-adjusted life-year
      ranges from 23,637 dollars to 42,785 dollars). CONCLUSIONS: Linezolid is a cost
      effective alternative to vancomycin for the treatment of ventilator-associated
      pneumonia.

PMID- 14707573
TI  - Effect of core body temperature on ventilator-induced lung injury.
AB  - OBJECTIVE: Ventilator-induced lung injury is a risk in patients requiring
      elevated ventilatory support pressures. We hypothesized that thermal stress
      modulates the development of ventilator-induced lung injury. DESIGN: Experimental
      study. SETTING: University laboratory. SUBJECTS: Anesthetized rabbits.
      INTERVENTIONS: Two experimental studies were designed to determine the role of
      temperature as a cofactor in ventilator-induced lung injury. In the first study,
      three groups of anesthetized rabbits were randomized to be ventilated for 2 hrs
      at core body temperatures of 33, 37, or 41 degrees C while ventilated with
      pressure control ventilation of 15/3 cm H2O (noninjurious settings-control) or
      35/3 cm H2O (potentially injurious settings-experimental). To exclude effects
      arising from cardiac output fluctuations or from extrapulmonary organs, an
      isolated lung model was used for the second study, perfused at a fixed rate and
      studied at either 33 degrees C or 41 degrees C. MEASUREMENTS AND MAIN RESULTS: In
      the first study, the hyperthermic group compared with the hypothermic animals had
      significantly reduced mean PaO2 (-114 vs. + 14 mm Hg, p <.05), increased lung
      edema formation (mean wet weight/dry weight ratio of 8.1 vs. 5.7), and altered
      pressure-volume curves. The hyperthermic isolated, perfused lungs had an
      increased ultrafiltration coefficient, formed more edema, and experienced greater
      alveolar hemorrhage than hypothermic lungs. CONCLUSIONS: In two studies of
      ventilator-induced lung injury in rabbits, maintaining hyperthermia compared with
      hypothermia augmented the development of lung injury. Similar results from both
      the in vivo and isolated, perfused lung studies suggest that the observed effects
      were not due to cardiovascular factors or consequences of heating nonpulmonary
      organs.

PMID- 14707574
TI  - Dopamine under alpha1-blockade, but not dopamine alone or fenoldopam, increases
      depressed gastric mucosal oxygenation.
AB  - OBJECTIVE: To compare the effects of dopamine, both in the presence and absence
      of alpha1-blockade, and fenoldopam on microvascular gastric mucosal oxygenation
      and systemic oxygen transport under compromised circulatory conditions, both
      without and with fluid resuscitation. DESIGN: Randomized controlled animal study.
      SETTING: University department of anesthesiology. SUBJECTS: Eight anesthetized
      dogs with chronically implanted ultrasound flow probes around the pulmonary
      artery for continuous measurement of cardiac output. INTERVENTIONS: On different
      days, the dogs received in random order either dopamine (2.5 and 5.0 microg.kg(
      1).min(-1), with or without alpha1-blocker pretreatment), the selective DA1
      agonist fenoldopam (0.1 and 1.0 microg.kg(-1).min(-1), with and without DA1
      blocker pretreatment), or saline (control). These interventions were performed
      under compromised cardiocirculatory conditions (induced by ventilation with
      positive end-expiratory pressure [PEEP] of 10 cm H2O), both without and with
      fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: We continuously measured
      regional microvascular hemoglobin saturation (microHbO2) in gastric mucosa by
      reflectance spectrophotometry and systemic oxygen transport ([U1E0A]O2).
      Ventilation with PEEP significantly decreased [U1E0A]O2 (from 19 +/- 2 to 9 +/- 1
      mL.kg(-1).min(-1), mean +/- sem) and gastric mucosal microHbO2 (from 57 +/- 2% to
      37 +/- 3%). Fluid resuscitation restored [U1E0A]O2 back to baseline (from 9 +/- 1
      to 19 +/- 2 mL.kg(-1).min(-1)) but only partially restored microHbO2 (from 37 +/-
      3% to 50 +/- 4%). Under both conditions, dopamine with and without alpha1
      blockade significantly increased [U1E0A]O2 (by about 5 mL.kg-1.min-1 in the
      nonresuscitated state and 10 mL.kg-1.min-1 in the fluid resuscitated state,
      respectively), but only dopamine in the presence of alpha1-blockade also
      significantly increased gastric mucosal microHbO2 (by 5 +/- 1% and 7 +/- 2% in
      the nonresuscitated and fluid resuscitated states, respectively). Fenoldopam
      under all study conditions did not significantly affect [U1E0A]O2 or microHbO2,
      either in the presence or absence of DA1-blockade. CONCLUSIONS: During
      compromised cardiocirculatory conditions, alpha1-receptor activation during
      dopamine infusion prevented an increase in gastric mucosal oxygenation.
      Furthermore, selective DA1-stimulation (by fenoldopam) was insufficient to
      overcome the PEEP-induced depression of microHbO2. The responses of gastric
      mucosal oxygenation did not parallel changes in systemic oxygen transport. These
      findings were independent of fluid resuscitation.

PMID- 14707575
TI  - Protective effects of M40401, a selective superoxide dismutase mimetic, on
      zymosan-induced nonseptic shock.
AB  - OBJECTIVE: Zymosan enhances formation of reactive oxygen species, which
      contributes to the pathophysiology of organ failure during nonseptic shock. Here
      we have investigated the effects of M40401, a new superoxide dismutase mimetic,
      on the organ failure associated with nonseptic shock caused by zymosan in rats.
      DESIGN: Experimental study. SETTING: Laboratory. SUBJECTS: Male Sprague-Dawley
      rats. INTERVENTIONS: We investigated the effects of M40401 on the organ failure
      associated with nonseptic shock caused by zymosan (500 mg/kg, administered
      intraperitoneally as a suspension in saline) in rats. MEASUREMENTS AND MAIN
      RESULTS: Organ failure and systemic inflammation in rats were assessed 18 hrs
      after administration of zymosan and/or M40401 and were monitored for 12 days (for
      loss of body weight and mortality). Treatment of rats with M40401 (10 mg/kg
      intraperitoneally, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation
      and the migration of polymorphonuclear cells caused by zymosan. M40401
      administration also attenuated the lung and intestinal injury (histology) as well
      as the increase in myeloperoxidase activity and malondialdehyde concentrations
      caused by zymosan in lung and intestine. Immunohistochemical analysis for
      nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose) revealed positive
      staining in lung and intestine from zymosan-treated rats. The degree of staining
      for nitrotyrosine and poly(adenosine 5'-diphosphate-ribose) was markedly reduced
      in tissue sections obtained from zymosan-treated rats administered with M40401.
      CONCLUSION: This study provides the first evidence that M40401 attenuates the
      degree of zymosan-induced nonseptic shock in the rat.

PMID- 14707576
TI  - Effects of cyclic opening and closing at low- and high-volume ventilation on
      bronchoalveolar lavage cytokines.
AB  - OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and
      high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING:
      University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley
      rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes.
      MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I
      (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to
      various modes of ventilation: a) opening and closing with positive end-expiratory
      pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and
      closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP
      0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning
      and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs
      were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage
      inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage.
      In study II (ventilation at high volumes), rat lungs (n = 45) were randomly
      assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak
      inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway
      pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the
      cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine
      concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2,
      and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low
      volume study, there was no difference in bronchoalveolar lavage cytokine
      concentrations between the PEEP group and the atelectatic group. All cytokines
      were significantly higher in the ZEEP group compared with the atelectasis group.
      Macrophage inflammatory protein-2 was significantly higher in the ZEEP group
      compared with the PEEP group. Lung compliance, as reflected by change in peak
      inspiratory pressure, was also significantly worse in the ZEEP compared with the
      PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin
      6 were significantly higher in the cyclic stretch group compared with the CPAP 31
      group. There was no significant difference between the cytokine concentrations in
      the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude
      that at low lung volumes, cyclic opening and closing from ZEEP leads to greater
      increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume
      ventilation, over time, the degree of overdistension is more associated with
      increases in bronchoalveolar lavage cytokines than cyclic opening and closing
      alone.

PMID- 14707577
TI  - Cocaine enhances susceptibility to endotoxemic shock in a subset of rats.
AB  - OBJECTIVE: We hypothesized that the sympathomimetic cocaine may alter
      cardiovascular and inflammatory responses and enhance susceptibility to
      endotoxemia due to innate differences in patterns of sympathetic and
      cardiovascular responsiveness. DESIGN: Prospective study. SETTING: Experimental
      animal laboratory. SUBJECTS: Fifty-six conscious, instrumented albino rats.
      INTERVENTIONS: Rats were instrumented for determination of arterial pressure and
      intravenous drug administration and, in some rats, for cardiac output. After
      recovery, rats were given cocaine (5 mg/kg i.v., twice daily with 4-6 trials) to
      identify one of two hemodynamic response patterns: a) an increase in systemic
      vascular resistance with cardiac depression (vascular responders) or b) smaller
      increases in systemic vascular resistance and no change or an increase in cardiac
      output (mixed responders). At least 1 month after characterizing response
      patterns to cocaine, animals were pretreated with cocaine (5 mg/kg i.v.) or an
      equivalent bolus of vehicle (0.9% saline) while recording hemodynamics. Five
      minutes later, Escherichia coli lipopolysaccharide (serotype O55:B5, 20 mg/kg
      i.v.) was administered for 15 mins. MEASUREMENTS AND MAIN RESULTS: Hemodynamic
      responses, pupillary diameter, and serum cytokines were determined at several
      time points. Lipopolysaccharide administration (5-40 mg/kg) without cocaine
      produced dose-dependent depressor responses with recovery typically within 2 hrs.
      Although 87% of rats survived a single 20 mg/kg dose of lipopolysaccharide when
      given alone, pretreatment of vascular responders with cocaine before
      lipopolysaccharide resulted in greater increases in systemic vascular resistance
      and pupillary mydriasis and lethality in five of six vascular responders, whereas
      only one of six mixed responders died. Pretreatment with the alpha1-adrenoceptor
      antagonist prazosin (0.1 mg/kg i.v.) before cocaine and lipopolysaccharide
      attenuated hemodynamic responses and improved survival among vascular responders.
      Serum interleukin-6 and interleukin-10 were elevated in rats treated with cocaine
      and lipopolysaccharide compared with rats treated with lipopolysaccharide alone,
      whereas serum tumor necrosis factor-alpha was reduced by cocaine pretreatment.
      Moreover, serum interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6
      were elevated in nonsurvivors compared with survivors after cocaine and
      lipopolysaccharide administration. CONCLUSIONS: We conclude that cocaine enhances
      susceptibility and worsens outcome from endotoxic shock by augmenting sympathetic
      activity, particularly in vascular responders, and that alpha-adrenoceptors
      mediate the altered inflammatory responses.

PMID- 14707578
TI  - N,N',N"-triacetylglucosamine, an inhibitor of lysozyme, prevents myocardial
      depression in Escherichia coli sepsis in dogs.
AB  - OBJECTIVE: Reversible myocardial depression in sepsis has been ascribed to the
      release of inflammatory mediators. We recently found that lysozyme c (Lzm-S),
      consistent with that originating from the spleen, was a mediator of myocardial
      depression in an Escherichia coli model of septic shock in dogs. We further
      showed in a right ventricular trabecular (RVT) preparation that Lzm-S's
      depressant activity could be blocked by N,N',N" triacetylglucosamine (TAC), a
      competitive inhibitor of Lzm-S. We hypothesized that Lzm-S binds to or cleaves a
      cardiac membrane glycoprotein, thereby interfering with myocardial contraction in
      sepsis. In the present study, we examined whether TAC could prevent myocardial
      depression in an in vivo preparation and whether other related N
      acetylglucosamine (NAG) structures could also inhibit Lzm-S's effect in RVT.
      DESIGN: Randomized experimental study. SETTING: University laboratory. SUBJECTS:
      Anesthetized, mechanically ventilated dogs. INTERVENTIONS: We produced sepsis by
      infusion of E. coli over an approximately 6-hr period. MEASUREMENTS AND MAIN
      RESULTS: We examined the effect of TAC on stroke work, our primary index of
      myocardial function, when treatment was administered before sepsis (pretreatment)
      and after 1.5 hrs (early treatment study) and 3.5 hrs of sepsis (late treatment
      study; LTS). In the pretreatment study and early treatment study, myocardial
      depression would have not yet occurred but would have already been present in the
      late treatment study. In RVT, we assessed the effect of other NAG
      oligosaccharides and variants to the NAG structure on Lzm-S's depressant
      activity. In pretreatment and the early treatment study, TAC prevented the
      reduction in stroke work observed in nontreated septic groups but did not reverse
      the reduction found in the late treatment study. In RVT, of the compounds tested,
      only N,N'-diacetylglucosamine showed an inhibitory effect. CONCLUSIONS: We found
      that TAC, a competitive inhibitor of Lzm-S, prevented myocardial depression in
      experimental sepsis. Only specific NAG structures are inhibitory to Lzm-S's
      depressant activity. TAC may be useful in attenuating cardiovascular collapse in
      sepsis.

PMID- 14707579
TI  - Arginine vasopressin compromises gut mucosal microcirculation in septic rats.
AB  - OBJECTIVE: Arginine vasopressin (AVP) is increasingly used in the therapy of
      septic patients with hypotension. However, its effects on the microvascular
      networks have not been studied in detail. This study was designed to determine
      the effects of AVP infusion on the villus microcirculation of the septic rat
      ileum. DESIGN: Prospective, placebo-controlled, randomized, single-blinded trial.
      SETTING: University research laboratory. SUBJECTS: Fifteen male Sprague-Dawley
      rats. INTERVENTIONS: Twenty-four hours after cecal ligation and perforation to
      create sepsis (M1), rats (n = 8) received a continuous AVP infusion to increase
      mean arterial pressure by 20 mm Hg (M2) and 40 mm Hg (M3) from M1. In the control
      group (n = 7), an equivalent volume of normal saline was infused. MEASUREMENTS
      AND MAIN RESULTS: Videomicroscopy was performed on 6-10 villi of ileum mucosa at
      M1 and was repeated at M2 and M3. Blood was drawn to determine plasma levels of
      AVP and interleukin-6. At M1, both study groups were hypotensive compared with
      preseptic data (mean arterial pressure, -25%). The increase in mean arterial
      pressure was linked to supraphysiologic AVP plasma levels and was accompanied by
      a decrease in mean mucosal blood flow by 76% at M2 and 81% at M3 (p <.001 vs.
      control). Red blood cell velocity fell by 45% and 47%, respectively (p <.05 vs.
      control). Whereas periods of arrested villus blood flow increased from 8.1 +/-
      2.6 secs/min to 43.8 +/- 5.2 and 47 +/- 6.2 secs/min at M2 and M3 (p <.001), the
      diameter of terminal arterioles remained unchanged. In addition, AVP infusion
      further augmented the sepsis-associated increase in interleukin-6 levels (AVP,
      905 +/- 160 vs. control, 638 +/- 55 pg/mL; p =.022). CONCLUSIONS: This study
      provides evidence for severe abnormalities in gut mucosal blood flow after AVP
      infusion in septic rats, accompanied by an augmented inflammatory response to the
      septic injury. The effects of AVP on microvascular blood flow in this model may
      be related to AVP activities on larger arterioles (>40 microm), a concomitant
      reduction in cardiac output, or even both.

PMID- 14707580
TI  - Assessment of the development of choked flow during total liquid ventilation.
AB  - OBJECTIVE: The flow rate of a liquid drainage from the lungs is limited because
      of the elastic nature of the airways. This study was designed to clarify the
      relationship between intrapulmonary liquid volume and the development of the flow
      limitation or choked flow phenomenon as a function of expiratory flow rate during
      total liquid ventilation with perflubron. DESIGN: Prospective animal study.
      SETTING: University research laboratory. SUBJECTS: Rabbits with a weight of 3.2
      +/- 0.3 kg. INTERVENTIONS: After the rabbits were killed, the lungs were filled
      to functional residual capacity with perflubron, followed by administration of an
      additional volume of 30, 45, or 60 mL of perflubron (initial volume = functional
      residual capacity + additional volume). MEASUREMENTS AND RESULTS: In one set of
      five animals, the intratracheal pressure at the occurrence of choked flow was
      established at -20 mm Hg. In another set of six animals, we demonstrated that the
      volume remaining in the lung at the point of development of choked flow (Vch) was
      stable for the first 40 mins after the animals were killed. Flow rates of 1.25,
      2.5, 3.75, 5.0, 7.5, 10.0, and 12.5 mL/sec were then applied at an additional
      volume of 30, 45, or 60 mL to 34 animals. Vch approximately doubled as the flow
      rate increased from 1.25 mL/sec to 12.5 mL/sec (p <.001). At the same flow, Vch
      was higher for an additional volume of 60 mL than 30 mL when the flow was > or
      =2.5 mL/sec. CONCLUSIONS: From these data, we conclude that choked flow occurs at
      intratracheal pressure of less than -20 mm Hg, that Vch is stable for the first
      40 mins after the animals are killed, and that Vch is a function of flow rate and
      initial volume.

PMID- 14707581
TI  - Efficacy of partial liquid ventilation in improving acute lung injury induced by
      intratracheal acidified infant formula: determination of optimal dose and
      positive end-expiratory pressure level.
AB  - OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used
      for acute lung injury induced by oleic acid or lung lavage. Positive end
      expiratory pressure (PEEP) during partial liquid ventilation enhances the
      efficacy of fluorocarbon. The aim of the current study was to assess whether
      partial liquid ventilation can repair lung damage induced by intratracheal
      acidified infant formula and to determine the optimal fluorocarbon dose and PEEP
      level. DESIGN: Prospective, randomized animal study. SETTING: University research
      laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits.
      INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal
      acidified infant formula in four groups. Next, three groups received 10, 15, or
      20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated.
      For study 2, acute lung injury was induced in five groups. One group was gas
      ventilated at a PEEP of 5 cm H2O, whereas the other four groups received
      fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10,
      or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute
      lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of
      15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide
      production of neutrophils, resulting in similar improvements in oxygenation, lung
      mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality
      from pneumothorax. In study 2, the combination of PEEP with partial liquid
      ventilation improved gas exchange, lung compliance, pulmonary edema, and
      histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm
      H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax
      and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and
      PEEP improved the physiologic, biochemical, and histologic lung injury induced by
      acidified infant formula. The beneficial effects of partial liquid ventilation
      are due, in part, to inhibition of pulmonary neutrophil accumulation and
      activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our
      model were 15 mL/kg and 10 cm H2O, respectively.

PMID- 14707582
TI  - Pro- and antifibrinolytic properties of human pulmonary microvascular versus
      artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha.
AB  - OBJECTIVE: Microvascular thrombosis is a common feature of acute inflammatory
      lung injury, as occurs in sepsis and acute respiratory distress syndrome, but the
      underlying pathomechanisms are presently not fully understood. DESIGN:
      Experimental. SETTING: University laboratory. SUBJECTS: Lung endothelial cells.
      INTERVENTIONS: We characterized the expression of tissue-type and urokinase-type
      plasminogen activator (t-PA and u-PA) as well as plasminogen activator inhibitor
      (PAI)-1 and PAI-2 in human endothelial cells (EC) from the microvascular
      pulmonary circulation (HMVEC-L) and compared it with that of EC from pulmonary
      artery (HPAEC) and umbilical vein (HUVEC) under baseline conditions and upon
      stimulation with either tumor necrosis factor-alpha or lipopolysaccharide.
      MEASUREMENTS AND MAIN RESULTS: Real-time reverse transcription-polymerase chain
      reaction and enzyme-linked immunosorbent assay were employed for quantification
      of messenger RNA and protein concentrations. Under baseline conditions,
      comparable PAI-1 expression was noted in all EC. HPAEC were characterized by
      significantly higher baseline expression of t-PA and PAI-2 compared with HUVEC
      and HMVEC-L. In contrast, u-PA messenger RNA concentrations were found to be
      significantly higher in nonstimulated HMVEC-L compared with HUVEC and HPAEC. In
      all EC, stimulation with tumor necrosis factor-alpha and lipopolysaccharide
      increased the expression of PAI-1, PAI-2, and u-PA and decreased t-PA expression.
      The changes in messenger RNA content were reflected by corresponding changes in
      the protein concentrations. CONCLUSIONS: High baseline u-PA expression is a
      prominent feature of human lung microvascular EC, whereas pulmonary artery EC are
      characterized by high t-PA concentrations. Microbial and inflammatory challenge
      provokes up-regulation of PAI-1 and PAI-2 and down-regulation of t-PA in both
      macro- and microvascular pulmonary EC, which may favor local fibrin deposition.

PMID- 14707584
TI  - Detection of ischemia by PCO2 before adenosine triphosphate declines in skeletal
      muscle.
AB  - OBJECTIVE: Ischemia is a serious problem in clinical medicine, and effective
      methods are needed to detect ischemia before the injury becomes irreversible. In
      experimental studies on several organs, PCO2 was found to increase rapidly after
      the onset of supply-dependent anaerobic metabolism. A shortcoming of these
      studies was that PCO2 was not correlated with tissue concentrations of lactate
      and the energy status in the cell. Thus, in this study we have measured tissue
      concentrations of lactate, phosphocreatine, and adenosine triphosphate. We
      hypothesized that during ischemic conditions, PCO2 reflects lactate generation in
      the cell and not exhausted energy stores per se. If this is the case, PCO2 can be
      used to detect ischemia before the energy stores are depleted. Consequently,
      therapy can be instituted at a time when the organ is salvageable. DESIGN:
      Prospective laboratory study. SETTING: University research laboratory. SUBJECTS:
      Seven pigs. INTERVENTIONS: In a porcine model, gluteal skeletal muscles with no
      flow ischemia were examined. PCO2 was measured both in situ and in vitro at
      increasing periods of time. Concomitantly, tissue lactate, adenosine
      triphosphate, and phosphocreatine were analyzed. MEASUREMENTS AND MAIN RESULTS:
      Tissue surface CO2 tension (PtCO2) increased rapidly after onset of ischemia.
      From a baseline of 63 +/- 3 torr (8.4 +/- 1.2 kPa) under aerobic conditions, it
      increased to 157 +/- 6 torr (21 +/- 2.2 kPa) after 30 mins of ischemia and 386 +/
      9 torr (51.5 +/- 3 kPa) at 120 mins. The rapid increase of PtCO2 correlated well
      with increasing values of lactate (r2 >.9) in the tissue. Adenosine triphosphate
      was essentially unchanged for 45 mins after onset of ischemia, after which it
      declined. Phosphocreatine decreased earlier than adenosine triphosphate in
      accordance with the notion that high-energy phosphate groups are transferred from
      phosphocreatine to adenosine triphosphate. CONCLUSION: In this porcine model of
      skeletal muscle ischemia, PtCO2 correlates well with tissue lactate and increases
      long before the energy stores of phosphocreatine and most notably adenosine
      triphosphate are severely reduced. Thus, PtCO2 could be monitored to detect and
      treat earlier stages of ischemia.

PMID- 14707583
TI  - Sesame oil protects against lipopolysaccharide-stimulated oxidative stress in
      rats.
AB  - OBJECTIVE: The aim of this study was to determine the effects and the defense
      mechanisms of sesame oil on lipopolysaccharide-induced oxidative stress in rats.
      DESIGN: Laboratory in vivo study of the effect of sesame oil on lipid peroxide,
      superoxide anion, superoxide dismutase, catalase, glutathione, and nitrite
      concentrations. To assess the effect of sesame oil on hepatic function, we
      determined serum aspartate aminotransferase, total bilirubin, and liver
      histology. SETTING: University laboratory. SUBJECTS: Male SPF Wistar rats.
      INTERVENTIONS: Blood testing, administration of oils, and liver biopsies.
      MEASUREMENTS AND MAIN RESULTS: Oxidative stress induced by lipopolysaccharide (5
      mg/kg, intraperitoneally) was assessed by determination of lipid peroxidation.
      Sesame oil was given orally immediately after lipopolysaccharide administration,
      and lipid peroxidation concentrations were determined. The reactive oxygen
      species superoxide anion was measured by chemiluminescence analyzer. The enzyme
      activities of superoxide dismutase and catalase and the concentrations of
      glutathione and nitrite also were determined. Hepatic injury was evaluated by
      determining the concentrations of serum aspartate aminotransferase and total
      bilirubin and by liver histologic examination. Sesame oil significantly reduced
      lipid peroxidation but failed to affect nitrite concentrations in
      lipopolysaccharide-treated rats. Superoxide anion counts were decreased, and
      glutathione, but not superoxide dismutase or catalase, was increased in sesame
      oil-treated groups with lipopolysaccharide-induced oxidative stress. Only sesame
      oil-treated groups, but not corn oil- or mineral oil-treated groups, showed
      attenuated hepatic disorder induced by lipopolysaccharide. In addition, sesame
      oil given 6 hrs after lipopolysaccharide also attenuated lipid peroxidation and
      hepatic disorder. Furthermore, sesame oil given immediately or 6 hrs after
      lipopolysaccharide administration significantly reduced morphologic changes
      induced by lipopolysaccharide. CONCLUSION: A single dose of sesame oil may
      attenuate oxidative stress and subsequently relieve hepatic disorder in
      endotoxemic rats.

PMID- 14707585
TI  - Spontaneous gasping generates cardiac output during cardiac arrest.
AB  - OBJECTIVES: To measure stroke volumes coincident with spontaneous gasping during
      untreated ventricular fibrillation and to evaluate the effects of gasping.
      DESIGN: Prospective study in laboratory animals. SETTING: University-affiliated
      research institute. SUBJECTS: Male Yorkshire-X domestic pigs. INTERVENTIONS: Pigs
      were anesthetized (ketamine, 20 mg/kg intramuscularly and sodium pentobarbital,
      30 mg/kg intravenously), intubated, and mechanically ventilated. Ventricular
      fibrillation was electrically induced and untreated for 7 mins. The right femoral
      artery and vein were cannulated. A 5.5/7.5-MHz biplanar transesophageal
      echocardiography transducer was advanced into the esophagus. MEASUREMENTS AND
      MAIN RESULTS: Stroke volumes were measured as the product of the transaortic
      blood flow velocity and transesophageal echocardiographic measurements of valve
      area. In addition, left ventricular volumes were echocardiographically estimated
      at peak inspiration and at peak expiration of each gasp by transesophageal
      methods. The stroke volume produced by gasping averaged 23 +/- 6 mL, which
      represented approximately 60% of a precardiac arrest stroke volume (38 +/- 8 mL,
      p <.001). Increases in end-tidal carbon dioxide tension coincident with each gasp
      were consistent with comparable increases in pulmonary blood flow and therefore
      stroke volumes. Both were associated with increases in aortic pressure from 20 +/
      3 to 33 +/- 8 mm Hg (p <.001) and coronary perfusion pressure from 4 +/- 3 to 13
      +/- 7 mm Hg (p <.001). CONCLUSIONS: Our studies confirm that preterminal gasping
      during ventricular fibrillation increases both ventilation and forward blood
      flow.

PMID- 14707586
TI  - Early impairment in consciousness predicts mortality after hemispheric ischemic
      stroke.
AB  - OBJECTIVE: Early predictors of poor outcome after acute ischemic stroke may be
      useful in selecting patients for potentially beneficial but high-risk
      interventions. DESIGN: Cohort study of patients given placebo in a randomized
      clinical trial. SETTING: Multicenter trial at 139 U.S. and 14 Canadian hospitals.
      PATIENTS: A cohort of 564 placebo-treated patients with major anterior
      circulation ischemic stroke enrolled in the Clomethiazole in Acute Stroke Study
      Ischemic Stroke (CLASS-I) trial. Patients did not have significant impairment in
      consciousness at baseline and were enrolled within 12 hrs of symptom onset.
      INTERVENTIONS: Prospective data collection of a number of clinical variables
      including use of a 6-point level of consciousness scale (1 = awake, 6 = no
      reaction to pain) to measure patients' level of consciousness at enrollment and
      12 additional times during the first 24 hrs after enrollment. The ability of
      level of consciousness score and additional clinical data to predict 30-day
      mortality was assessed. MEASUREMENTS AND MAIN RESULTS: At 1 month, 114 of 564
      patients (20%) had died. In univariate analysis, factors significantly associated
      with mortality included older age, white race, higher National Institutes of
      Health Stroke Scale score, higher serum glucose, atrial fibrillation, and any
      impairment in level of consciousness (p <.05). After controlling for these
      factors, increasing level of consciousness score at 3 hrs after enrollment and at
      all but one subsequent time point was significantly associated with increased
      mortality (odds ratio, 1.8 per point; 95% confidence interval, 1.2-2.6; p =.003
      at 3-hr time point). Maximum level of consciousness score during the initial 24
      hrs of monitoring also predicted mortality (odds ratio, 1.9 per point; 95%
      confidence interval, 1.4-2.5; p <.001). CONCLUSION: The development of a
      decreased level of consciousness within the initial hours after stroke onset, as
      evaluated by a simple six-point scale, is a powerful independent predictor of
      mortality after major anterior circulation ischemic stroke.

PMID- 14707587
TI  - Effects of feeding on gastric tonometric measurements in critically ill children.
AB  - OBJECTIVE: To determine the effect of gastric feeding on the measurement of
      gastric intramucosal PCO2 (PiCO2) and its derived gastric intramucosal PCO2
      arterial PCO2 difference (PiCO2-PaCO2 difference) and gastric intramucosal pH
      (pHi) in a group of critically ill children using recirculating gas tonometry.
      DESIGN: Prospective clinical pilot study. SETTING: Sixteen bed pediatric
      intensive care unit. PATIENTS: Ten mechanically ventilated and hemodynamically
      stable children (median age, 20.1 months [interquartile range (IQR), 9.7-47.6
      months] and median weight, 10.2 kg [IQR, 10-16.5 kg]). INTERVENTIONS: A 7-French
      recirculating gas tonometer was placed in the stomach via the orogastric route.
      MEASUREMENTS: In each patient, baseline fasted/unfed PiCO2, PiCO2-PaCO2
      difference, and pHi were determined hourly over a 5-hr period. Gastric feeding
      was then reestablished (3 mL/kg/hr) within a median time of 3 hrs and a further 5
      hourly measurements were determined. Concurrent arterial blood gas and lactate
      measurements were taken. Blood pressure and heart rate was monitored throughout.
      MAIN RESULTS: Hemodynamic parameters remained stable throughout the study period.
      When compared with the unfed/fasting state, PiCO2 measurements and PiCO2-PaCO2
      difference were consistently lower and pHi values higher than when the patients
      were fed (two-way analysis of variance for repeated measures: all p <.001 between
      groups). Measurements did not vary over time. CONCLUSIONS: In our patient group,
      gastric feeding decreased the PiCO2 and PiCO2-PaCO2 difference and increased pHi
      compared with the unfed state. These findings are in contrast to those found in
      adult studies.

PMID- 14707588
TI  - Ventilatory management of acute respiratory distress syndrome: a consensus of
      two.
AB  - OBJECTIVE: To synthesize the emerging body of experimental, observational, and
      clinical trial data into a practical guideline for safe and effective ventilatory
      management of acute respiratory distress syndrome. DATA SOURCES: Relevant, peer
      reviewed, scientific literature and personal observations from clinical practice.
      STUDY SELECTION: Relevant experimental studies and high-impact observational and
      clinical trials of acute respiratory distress syndrome management. DATA
      EXTRACTION: Detailed review of information contained in published scientific
      work. DATA SYNTHESIS: Interactive discussions between the authors that culminated
      in our consensus view of appropriate management. CONCLUSIONS: Prevention of
      ventilator-induced lung injury while accomplishing the essential life-supporting
      roles of mechanical ventilation is a complex undertaking that requires
      application of principles founded on a broad experimental and clinical database
      and on the results of well-executed clinical trials. At the bedside, execution of
      an effective lung-protective ventilation strategy remains an empirical process
      best guided by integrated physiology and a readiness to revise the management
      approach depending on the individual's response.

PMID- 14707589
TI  - Guidelines for the inter- and intrahospital transport of critically ill patients.
AB  - OBJECTIVE: The development of practice guidelines for the conduct of intra- and
      interhospital transport of the critically ill patient. DATA SOURCE: Expert
      opinion and a search of Index Medicus from January 1986 through October 2001
      provided the basis for these guidelines. A task force of experts in the field of
      patient transport provided personal experience and expert opinion. STUDY
      SELECTION AND DATA EXTRACTION: Several prospective and clinical outcome studies
      were found. However, much of the published data comes from retrospective reviews
      and anecdotal reports. Experience and consensus opinion form the basis of much of
      these guidelines. RESULTS OF DATA SYNTHESIS: Each hospital should have a
      formalized plan for intra- and interhospital transport that addresses a)
      pretransport coordination and communication; b) transport personnel; c) transport
      equipment; d) monitoring during transport; and e) documentation. The transport
      plan should be developed by a multidisciplinary team and should be evaluated and
      refined regularly using a standard quality improvement process. CONCLUSION: The
      transport of critically ill patients carries inherent risks. These guidelines
      promote measures to ensure safe patient transport. Although both intra- and
      interhospital transport must comply with regulations, we believe that patient
      safety is enhanced during transport by establishing an organized, efficient
      process supported by appropriate equipment and personnel.

PMID- 14707590
TI  - Guidelines for critical care medicine training and continuing medical education.
AB  - OBJECTIVE: Critical care medicine trainees and faculty must acquire and maintain
      the skills necessary to provide state-of-the art clinical care to critically ill
      patients, to improve patient outcomes, optimize intensive care unit utilization,
      and continue to advance the theory and practice of critical care medicine. This
      should be accomplished in an environment dedicated to compassionate and ethical
      care. PARTICIPANTS: A multidisciplinary panel of professionals with expertise in
      critical care education and the practice of critical care medicine under the
      direction of the American College of Critical Care Medicine. SCOPE: Physician
      education in critical care medicine in the United States should encompass all
      disciplines that provide care in the intensive care unit and all levels of
      training: from medical students through all levels of postgraduate training and
      continuing medical education for all providers of clinical critical care. The
      scope of this guideline includes physician education in the United States from
      residency through ongoing practice after subspecialization. DATA SOURCES AND
      SYNTHESIS: Relevant literature was accessed via a systematic Medline search as
      well as by requesting references from all panel members. Subsequently, the
      bibliographies of obtained literature were reviewed for additional references. In
      addition, a search of organization-based published material was conducted via the
      Internet. This included but was not limited to material published by the American
      College of Critical Care Medicine, Accreditation Council for Graduate Medical
      Education, Accreditation Council for Continuing Medical Education, and other
      primary and specialty organizations. Collaboratively and iteratively, the task
      force met, by conference call and in person, to construct the tenets and
      ultimately the substance of this guideline. CONCLUSIONS: Guidelines for the
      continuum of education in critical care medicine from residency through specialty
      training and ongoing throughout practice will facilitate standardization of
      physician education in critical care medicine.

PMID- 14707591
TI  - Role of adenosine in immunomodulation: review of the literature.
AB  - OBJECTIVE: Advances in the understanding of sepsis have failed to deliver
      satisfactory new treatments aimed at attenuating inflammatory-mediated organ
      dysfunction. Phagocytic cells play a pivotal role in driving the inflammatory
      response and causing direct tissue injury. Adenoreceptor stimulation may
      attenuate such inflammatory-mediated damage by down-regulating phagocytic
      activity and preventing excessive respiratory burst activation. DATA: A Medline
      database was used to perform a literature search for all articles relating to the
      use of adenosine as an immunomodulatory agent. CONCLUSION: There is convincing
      evidence to suggest that adenoreceptor modulation can prevent tissue injury
      through a variety of pathways. The use of adenosine modulation in
      ischemia/reperfusion injury has been the subject of considerable investigation,
      although experience with its use in sepsis is limited.

PMID- 14707592
TI  - Rapidly advancing necrotizing fasciitis caused by Photobacterium (Vibrio)
      damsela: a hyperaggressive variant.
AB  - OBJECTIVE: To describe the first case of Vibrio damsela necrotizing fasciitis in
      New England, emphasizing the importance of very early operative intervention to
      achieve source control in this extremely aggressive infection. DESIGN: Case
      report. SETTING: Surgical intensive care unit at Tufts-New England Medical Center
      in Boston, MA. PATIENT: A 69-yr-old retired fisherman with rapidly progressive
      necrotizing fasciitis from Photobacterium (Vibrio) damsela infection and ensuing
      multiple-system organ failure. INTERVENTIONS: Surgical debridement, ventilator
      support, vasopressors, continuous veno-venous hemofiltration, and blood product
      transfusions. MEASUREMENTS AND MAIN RESULTS: Death. CONCLUSIONS: A high index of
      suspicion is necessary for the diagnosis of this specific pathogen and concordant
      infection. The willingness to surgically debride and amputate without hesitation
      at a very early point may be the only intervention capable of saving the lives of
      patients affected by Photobacterium (Vibrio) damsela.

PMID- 14707593
TI  - Mediator modulation therapy of severe sepsis and septic shock: does it work?

PMID- 14707594
TI  - Pro: Multiplier.

PMID- 14707595
TI  - Con: Is the tele-intensive care unit ready for prime time?

PMID- 14707596
TI  - Anemia and blood transfusion in the critically ill: a decade without change.

PMID- 14707597
TI  - Age and functional status as determinants of intensive care unit outcome: sound
      basis for health policy or tip of the outcomes iceberg.

PMID- 14707598
TI  - Cardiogenic shock: art and science.

PMID- 14707599
TI  - Are we ready to monitor for delirium in the intensive care unit?

PMID- 14707600
TI  - How relaxed should we be with acute respiratory distress syndrome?

PMID- 14707601
TI  - Can endotracheal tube occlusion be predicted?

PMID- 14707602
TI  - Caveats of evaluating costs in critical care.

PMID- 14707603
TI  - Optimization of intestinal mucosal oxygenation in shock: a role for medical
      therapy?

PMID- 14707604
TI  - Relative importance of stretch and shear in ventilator-induced lung injury.

PMID- 14707605
TI  - Leukocyte lysozyme: a novel cause of septic myocardial depression?

PMID- 14707606
TI  - Transit care medicine--a critical link.

PMID- 14707607
TI  - Bacterial infection.

PMID- 14707608
TI  - Monitoring right-to-left intracardiac shunt in acute respiratory distress
      syndrome.

PMID- 14707609
TI  - Acute management of severe traumatic brain injury.

PMID- 14707610
TI  - Optimal discard volumes for arterial blood analysis.

PMID- 14707611
TI  - Recombinant activated protein C.

PMID- 14707612
TI  - Defining disseminated intravascular coagulation.

PMID- 14707613
TI  - Normality.

PMID- 14707614
TI  - Induced hypothermia in traumatic brain injury: effective if properly employed.

PMID- 14707615
TI  - Early goal-directed therapy.

PMID- 14707616
TI  - Cardiovascular management of septic shock.

PMID- 14707617
TI  - A comparison of the effects of the Latham-Millard procedure with those of a
      conservative treatment approach for dental occlusion and facial aesthetics in
      unilateral and bilateral complete cleft lip and palate: part I. Dental occlusion.
AB  - The purpose of this study was to compare the effect of the Latham-Millard
      presurgical orthopedics, gingivoperiosteoplasty, and lip adhesion protocol with
      conservative treatment (nonpresurgical orthopedics without
      gingivoperiosteoplasty) for palatal and dental occlusion in complete bilateral
      and complete unilateral cleft lip and palate. All patients were from the South
      Florida Cleft Palate Clinic. A retrospective dental occlusal study was conducted
      using serial dental casts that had been taken of patients from birth to 12 years
      of age. All surgical procedures, except for the secondary alveolar bone grafts in
      the conservative, nonpresurgical orthopedics group, were performed by D. Ralph
      Millard, Jr. Ralph Latham supervised the presurgical orthopedics cases. Samuel
      Berkowitz collected and analyzed all the serial records from 1960 to 1996. Among
      the patients with complete unilateral cleft lip and palate, 30 patients were
      treated with presurgical orthopedics, gingivoperiosteoplasty, and lip adhesion
      (the Latham-Millard protocol) and 51 patients were treated conservatively (i.e.,
      nonpresurgical orthopedics without gingivoperiosteoplasty). Among the patients
      with complete bilateral cleft lip and palate, 21 patients were treated with the
      Latham-Millard protocol and 49 patients were treated conservatively. Conservative
      treatment was performed between 1960 and 1980. In patients with bilateral cleft
      lip and palate, a head bonnet with an elastic strip was used to ventroflex the
      protruding premaxilla. In all patients (unilateral and bilateral cleft), lip
      adhesion was performed at 3 months followed by definitive lip surgery at 6 to 8
      months and palatal cleft closure between 18 and 24 months of age, in most cases.
      The Latham-Millard procedure was performed from 1980 to 1996; in bilateral cleft
      patients, it involved the use of a fixed palatal orthopedic appliance to bodily
      retract the protruding premaxilla and align it within the alveolar segments soon
      after birth. In all patients (unilateral and bilateral cleft), palatal alignment
      was also followed by gingivoperiosteoplasty and lip adhesion. Definitive lip
      surgery was performed between 6 and 8 months of age, and palatal closure was
      performed between 8 and 24 months of age using the von Langenbeck procedure with
      a modified vomer flap. All of the study participants had cleft lips and palates
      of either the unilateral or bilateral type; the unilateral and bilateral groups
      were further subdivided based on whether they had received the Latham-Millard
      protocol or the conservative treatment. It was then determined how many in each
      of these four basic groups had either anterior or buccal crossbites at four
      different age levels, when they were approximately 3, 6, 9, and 12 years of age.
      Although several children entered the study at or just before age 6, every
      patient in the 9-year-old and 12-year-old sample groups had been in the 6-year
      old group and all of the 12-year-olds had been included in the immediate
      preceding age sample. Two-by-two chi-square tests were carried out within each
      cleft type (unilateral or bilateral) at each of the four age levels separately,
      to test whether the treatment groups (protocol versus conservative) differed in
      the frequency of cases with a given kind of crossbite (rather than not having
      that kind of crossbite). At every age level, a greater percentage of patients
      treated with the Latham-Millard protocol developed crossbites than did those
      treated more conservatively. This difference existed for both the anterior and
      buccal crossbites and for both unilateral and bilateral clefts. Chi-square tests
      of the treatment differences in crossbite frequency showed that in three quarters
      of the Latham-Millard protocol versus conservative treatment comparisons (12 out
      of 16), a significantly greater frequency of crossbite cases occurred after the
      Latham-Millard protocol treatment as compared with after the conservative
      procedure. The chi-square values for the differences in outcome between the two
      kinds of treatment procedures were greater for the anterior crossbites than for
      the buccal crossbites, suggesting that the Latham-Millard protocol, relative to
      the conservative method, was more likely to have an adverse effect on the
      anterior crossbites than on the buccal crossbites. For those patients born with a
      bilateral cleft, the differences in crossbite frequency between the protocol and
      the conservative treatment were statistically significant for patients with an
      anterior crossbite but not for patients with a buccal crossbite. The analysis
      shows that in complete bilateral and unilateral cleft lip and palate, the
      frequency of the anterior crossbite and (except for ages 3 and 12) the buccal
      crossbite is significantly higher with the Latham-Millard presurgical
      orthopedics, gingivoperiosteoplasty, and lip adhesion protocol compared with the
      conservative, nonpresurgical orthopedics without gingivoperiosteoplasty
      treatment. The exception in the bilateral buccal case may be attributed to the
      small experimental sample size, which brings down the confidence level.

PMID- 14707618
TI  - Total lower lip reconstruction with a composite radial forearm-palmaris longus
      tendon flap: a clinical series.
AB  - Large, full-thickness lip defects after head and neck surgery continue to be a
      challenge for reconstructive surgeons. The reconstructive aims are to restore the
      oral lining, the external cheek, oral competence, and function (i.e.,
      articulation, speech, and mastication). The authors' refinement of the composite
      radial forearm-palmaris longus free flap technique meets these criteria and
      allows a functional reconstruction of extensive lip and cheek defects in one
      stage. A composite radial forearm flap including the palmaris longus tendon was
      designed. The skin flap for the reconstruction of the intraoral lining and the
      skin defect was folded over the palmaris longus tendon. Both ends of the
      vascularized tendon were laid through the bilateral modiolus and anchored with
      adequate tension to the intact orbicularis muscle of the upper lip. This
      procedure was used in 12 patients. Six patients had cancer of the lower lip, five
      patients had a buccal cancer involving the lip, and one patient had a primary gum
      cancer that extended to the lower lip. Total to near-total resection (more than
      80 percent) of the lower lip was indicated in six patients. In two other
      patients, the cancer ablation included more than 80 percent of the lower lip and
      up to 40 percent of the upper lip. A radial forearm palmaris longus free flap was
      used in all cases for reconstruction of the defect. Free flap survival was 100
      percent. At the time of final evaluation, which was 1 year after the operation,
      all patients had good oral continence at rest (static suspension) and had
      achieved sufficient oral competence when eating. Ten patients were able to resume
      a regular diet, and two patients could eat a soft diet. All patients regained
      normal or near-normal speech and had an acceptable appearance. The described
      refinement of the composite radial palmaris longus free flap technique allows the
      reconstruction of the lower lip with a functioning oral sphincter; the technique
      can be recommended for patients who need large lower lip resection. It provides
      functional recovery of the reconstructed lower lip synchronizing with the
      remaining upper lip.

PMID- 14707619
TI  - Craniofacial deformity in patients with uncorrected congenital muscular
      torticollis: an assessment from three-dimensional computed tomography imaging.
AB  - Congenital muscular torticollis is caused by idiopathic fibrosis of the
      sternocleidomastoid muscle that restricts movement and pulls the head toward the
      involved side. Deformation of the craniofacial skeleton will develop if the
      restriction is not released and result in aesthetic and functional problems. The
      purpose of this study was to use three-dimensional computed tomography imaging
      for qualitative and quantitative evaluation of the craniofacial deformity in a
      series of patients with uncorrected congenital muscular torticollis, and to
      assess age as a precipitating factor for severity of the deformity. A total of 14
      patients from 1 month to 24 years of age were included. The skull images were
      rotated into standard orientation and reconfigured for evaluation of the cranium,
      endocranial base, and facial skeletal structures. The midlines of cranial base
      and facial bone, angle of midline deviation, width of each hemicranium and
      hemiface, and the orbital index were defined and measured. The results showed
      that the cranium and cranial base deformation took place as early as in infant
      stage, with the most prominent change occurring in the posterior cranial fossa.
      Facial bone asymmetry started to appear after 5 years of age, at which time the
      mandibular and occlusal abnormalities were observed. The deformity of the orbits
      and maxilla occurred at an older age, characterized by the deviation and
      decreased vertical height on the affected side. The severity of the observed
      deformities increased with age. The angle of midline deviation was 2.48 +/- 1.68
      degrees in the cranial base and 3.26 +/- 3.28 degrees on the facial bone. Both of
      the midline deviations were significantly correlated with age. Compared with the
      contralateral side, the width of the ipsilateral posterior hemicranium was longer
      (54.36 +/- 6.72 mm versus 50.81 +/- 6.55 mm), and the width of the ipsilateral
      lower hemiface was shorter (35.30 +/- 7.27 mm versus 43.49 +/- 11.34 mm). Both
      differences were statistically significant. Measurement of the orbital index
      demonstrated a significantly flatter orbit on the ipsilateral side (89.48 +/-
      0.11 versus 92.74 +/- 0.08). This study showed that the cranium and cranial base
      deformity occurred early in patients with uncorrected torticollis, while the
      facial bone deformity occurred in childhood stage. The cranial and facial
      deformity became more severe with age. Early release of the muscle restriction is
      advised to prevent craniofacial deformation.

PMID- 14707620
TI  - Reconstruction of orbital floor fracture using solvent-preserved bone graft.
AB  - The orbital floor is one of the most frequently damaged parts of the
      maxillofacial skeleton during facial trauma. Unfavorable aesthetic and functional
      outcomes are frequent when it is treated inadequately. The treatment consists of
      spanning the floor defect with a material that can provide structural support and
      restore the orbital volume. This material should also be biocompatible with the
      surrounding tissues and easily reshaped to fit the orbital floor. Although
      various autografts or synthetic materials have been used, there is still no
      consensus on the ideal reconstruction method of orbital floor defects. This study
      evaluated the applicability of solvent-preserved cadaveric cranial bone graft and
      its preliminary results in the reconstruction of the orbital floor fractures.
      Twenty-five orbital floor fractures of 21 patients who underwent surgical repair
      with cadaveric bone graft during a 2-year period were included in this study.
      Pure blowout fractures were determined in nine patients, whereas 12 patients had
      other accompanying maxillofacial fractures. Of the 21 patients, 14 had clinically
      evident diplopia (66.7 percent), 12 of them had enophthalmos (57.1 percent), and
      two of them had gaze restriction preoperatively. Reconstruction of the floor of
      the orbit was performed following either the subciliary or the transconjunctival
      approach. A cranial allograft was placed over the defect after sufficient
      exposure. The mean follow-up period was 9 months. Postoperative diplopia,
      enophthalmos, eye motility, cosmetic appearance, and complications were
      documented. None of the patients had any evidence of diplopia, limited eye
      movement, inflammatory reactions in soft tissues, infection, or graft extrusion
      in the postoperative period. Providing sufficient orbital volume, no graft
      resorption was detected in computed tomography scan controls. None of the
      implants required removal for any reason. Enophthalmos was seen in one patient,
      and temporary scleral show lasting up to 3 to 6 weeks was detected in another
      three patients. Satisfactory cosmetic results were obtained in all patients. This
      study showed that solvent-preserved bone, which is a nonsynthetic, human
      originated, processed bioimplant, can be safely used in orbital floor repair and
      can be considered as another reliable treatment alternative.

PMID- 14707621
TI  - Septal fracture in simple nasal bone fracture.
AB  - SUMMARY: Nasal bone fractures are the most common type of facial fractures.
      Previous studies have shown that most nasal fractures involve the septum, which
      can provide an obstacle to the successful reduction of nasal bone fractures. In
      particular, septal fractures in combination with simple nasal bone fractures are
      usually unrecognized and untreated at the time of injury. Furthermore, systemized
      treatment protocols and diagnostic tools for septal fractures in the case of
      simple nasal bone fracture have not previously been presented. In this study, the
      clinical findings of septal fractures in cases of simple nasal bone fracture were
      correlated with symptoms, signs, and computed tomography findings and assessed
      statistically. The patterns of septal fractures in simple nasal bone fractures
      were assessed by direct vision via hemitransfixion incision. Of the 52 patients
      with simple nasal bone fracture who presented over a 3-year period and were
      included in this study, 10 were female and 42 were male, with an average age of
      33.8 years (age range, 18 to 61 years). Fifty of these patients (96.2 percent)
      showed septal fractures, and septoplasty or submucosal resection was performed on
      41 patients (78.8 percent) who manifested severe septal fractures of
      perioperative septal grade 3 or higher. Closed reduction of the nasal bone
      fracture only was performed on the remaining 11 patients. Among the signs evident
      at physical examination, mucosal tearing was found to be statistically
      significant for septal fracture. Computed tomography was found to be very helpful
      in diagnosing septal fracture but could not predict its severity accurately
      (Spearman correlation coefficient between computed tomography septal grading and
      perioperative septal grading, 33.5 percent). Therefore, computed tomography could
      not be used as a definitive diagnostic modality for septal fractures in terms of
      deciding whether septoplasty or submucous resection was needed. It is evident
      that septal fractures are frequent in simple nasal bone fractures that are not
      combined with other facial bone fractures. This study confirms that there are
      differences between radiologic findings and perioperative findings. To reduce the
      incidence of posttraumatic nasal deformity, meticulous physical examinations with
      subsequent septoplasty or submucosal resection are needed in the treatment of
      simple nasal bone fracture.

PMID- 14707622
TI  - Management of parotid hemangioma in 100 children.
AB  - Most problematic infantile hemangiomas are successfully treated with
      pharmacological therapy. However, there are reports that hemangioma of the
      parotid gland responds poorly to corticosteroid and interferon. To better clarify
      the management of parotid hemangioma, the authors retrospectively studied the
      records of 100 consecutive patients, seen between 1975 and 2002. The
      characteristics of the tumor, including sex ratio, presence at birth, size, side,
      complications, and involvement of adjacent structures, were recorded. The
      indications for and response to treatment and the need for surgical procedures
      were documented and statistically analyzed. The female-to-male ratio was 4.5:1.
      Forty percent of parotid hemangiomas were on the right side, 36 percent were on
      the left, and 24 percent were bilateral. Forty-five percent of patients had a
      premonitory cutaneous lesion at birth. Fifty-nine percent of parotid hemangiomas
      ulcerated during the early proliferative phase. Eighty-eight percent involved
      nearby structures (ear, 70 percent; lip, 34 percent; subglottic region, 21
      percent; eye, 18 percent; and nose, 3 percent). Seven percent of patients
      required tracheostomy, and 3 percent had signs of congestive heart failure.
      Seventy infants received pharmacological treatment. Sixty-seven patients were
      initially managed with corticosteroids; regression or stabilization was noted in
      83 percent of tumors (56 of 67 tumors). Twenty-one patients received interferon:
      11 in whom corticosteroid therapy had failed, seven in whom the tumor stabilized
      with corticosteroid therapy but further regression was needed, and three who had
      interferon as primary therapy. Ninety-five percent of the lesions that were
      resistant to corticosteroid subsequently responded to interferon alfa-2a or -2b.
      The overall response rate to pharmacological therapy was 98 percent. A
      reconstructive procedure was necessary during the involuting or involuted phase
      in 66 percent of patients: 92 percent had preauricular excision of redundant skin
      and/or fibrofatty tissue and 37 percent of patients had auricular revision. In
      summary, drug therapy was effective in the majority of infants with parotid
      hemangioma, whether given because the tumor was large, deforming, ulcerated, or
      involved nearby structures with functional consequences. Infantile hemangioma in
      the parotid gland responded to pharmacological treatment in a similar manner as
      hemangioma in other locations.

PMID- 14707623
TI  - Anterior neck reconstruction with pre-expanded free groin and scapular flaps.
AB  - To improve aesthetic and functional outcomes in the reconstruction of severe
      anterior neck burn deformities and to reduce donor-site morbidity, pre-expansion
      of free-flap donor sites was performed in eight patients. In the first stage of
      reconstruction, the tissue expander was placed and gradually inflated over a
      period of 6 weeks. In the second stage, the anterior neck scar was resected up to
      the limits of the aesthetic unit of the neck, radical release of neck contracture
      was achieved by transection of contracted platysma muscle, and immediate coverage
      with a pre-expanded groin or scapular free flap was performed. The early
      postoperative course was uneventful. Physical therapy was started 1 week after
      the reconstruction. Long-term follow-up (mean, 4 years) of patients who underwent
      reconstruction of extensive neck burn deformities demonstrated good aesthetic and
      functional results. The advantages and drawbacks of using pre-expanded free flaps
      in the treatment of neck burn contractures are discussed.

PMID- 14707624
TI  - Anterior thoracic hypoplasia: a separate entity from Poland syndrome.
AB  - SUMMARY: Women presenting with anterior thoracic depression, breast hypoplasia,
      and subsequent asymmetry are often diagnosed with Poland syndrome regardless of
      pectoralis involvement, or are placed in the generic category of breast asymmetry
      or skeletal dysplasias. Recently, though, the term "sunken chest" has been used
      to describe forms of chest wall depression that previously may have fallen under
      generic skeletal dysplasias. The authors believe that, combined with hypoplasia
      of the ipsilateral breast, superior location of the nipple-areola complex
      compared with the contralateral side, and normal pectoralis muscles, this
      represents a previously undefined and real condition called anterior thoracic
      hypoplasia. During the past 4 years, the authors have treated eight women who
      have presented with a diagnosis of Poland syndrome or pectus excavatum, all of
      whom share the same characteristics-unilateral sunken anterior chest wall,
      hypoplasia of the breast, superiorly placed nipple-areola complex, normal
      pectoralis muscle, and normal sternal position. All of the patients underwent
      correction of breast asymmetry and unilateral anterior thoracic hypoplasia with
      augmentation mammaplasty, a method that when tailored for each side yields good
      aesthetic results. The average age of the patients was 31 years and the average
      chest size was 34. Cup size, as measured by the patient's standard bra, was a B
      on the nonaffected side in all patients and an A on the affected side in all
      patients except one. Of the eight patients, seven had the right anterior chest
      and breast involved, whereas one patient had involvement on the left. For all of
      the patients, the nipple and areola of the hypoplastic side were smaller and in a
      more superior position compared with the contralateral side on visual inspection.
      In the eight patients, a total of 19 augmentations (15 primary augmentations and
      four revisions) and one mastopexy were performed. Ten inframammary-fold
      approaches and nine periareolar approaches were used, and all of the implants
      were placed in a partial submuscular position, except for two implants placed in
      a subglandular position that were converted to partial submuscular positions in a
      secondary setting. In all the women, the sternal head of the pectoralis muscle
      was present and the pectoralis muscle appeared to be equal in size compared to
      the contralateral side. Nine different types of implants were used. Average
      implant fill volume measured 412 cc on the hypoplastic side and 257 cc on the
      contralateral side. In follow-up, all of the patients were satisfied with their
      operation and rated their aesthetic outcome as very good to excellent. The
      authors believe that anterior thoracic hypoplasia is a real, previously
      misdiagnosed and undescribed condition, and that both chest wall and breast
      deformities can be corrected safely and with excellent results using proper
      augmentation planning and implant selection.

PMID- 14707625
TI  - Segmental mandibulectomy and immediate free fibula osteoseptocutaneous flap
      reconstruction with endosteal implants: an ideal treatment method for mandibular
      ameloblastoma.
AB  - Thirteen patients with large ameloblastomas of the mandible underwent segmental
      mandibulectomy and immediate reconstruction, with simultaneous placement of
      osseointegrated implants. All patients received palatal mucosal grafts around the
      dental implants 6 to 10 months after surgical treatment and received implant
      supported prostheses another 1 to 2 months later. There were five female and
      eight male patients, with a mean age of 32 years (range, 17 to 50 years). The
      mean length of the mandibular defect was 8.8 cm (range, 5 to 13 cm). All free
      fibula flap procedures were successful, with no reexplorations or partial flap
      losses. There was no clinical or radiographic evidence of failure during the
      osseointegration process for any implant. With functional occlusal loading, the
      marginal bone loss around the implants was less than 1.5 mm in a mean follow-up
      period of 40 months (range, 18 to 70 months). There were no recurrences during
      that time. The technique described allows improved access to the bone at the time
      of reconstruction, immediate assessment of alveolar ridge relationships, and
      accurate fixation of the implant-fibula construct. The advantages of this
      procedure include a reduced risk of recurrence with segmental resection, reliable
      mandibular reconstruction, and reduction of the number of surgical procedures,
      allowing full oral rehabilitation in a shorter time. It is concluded that
      segmental mandibulectomy and immediate vascularized fibula osteoseptocutaneous
      flap reconstruction, with simultaneous placement of osseointegrated implants,
      represent an ideal treatment method for large ameloblastomas of the mandible.

PMID- 14707626
TI  - Functional rehabilitation of the atrophic mandible and maxilla with fibula flaps
      and implant-supported prosthesis.
AB  - Historically, nonvascularized bone grafts have been the standard treatment for
      severe mandibular and maxillary atrophy, followed by immediate or delayed implant
      placement. Extreme atrophy is an unfavorable biological and mechanical location
      for nonvascularized autologous bone transplants. The authors present the results
      of a multidisciplinary treatment protocol for rehabilitation of extreme
      mandibular and maxillary atrophy by use of the vascularized fibular flap. This
      protocol includes bone augmentation, implant surgery, soft-tissue management, and
      prosthetic restoration. Since 1993, 18 patients with a mean age of 47.5 years
      presented with extreme mandibular and/or maxillary atrophy and underwent alveolar
      crest augmentation with vascularized fibular flaps. Bone healing was achieved in
      17 of the 18 patients. Seventy-three osteointegrated implants were inserted in 12
      of 17 fibular flaps. Altogether, 62 implants were loaded and 11 dental prostheses
      were made. Average follow-up of the loaded implants was 41 months. The success
      rate of loaded implants was 100 percent. The authors strongly recommend the use
      of the fibular bone flap when dealing with extreme atrophy of the mandible and
      maxilla and suggest the protocol outlined in this review.

PMID- 14707628
TI  - Perforator flaps from the lateral lower leg for intraoral reconstruction.
AB  - Perforator flaps are based on cutaneous, small-diameter vessels that originate
      from a main pedicle and perforate fascia or muscle to reach the skin. Although
      these flaps have recently become popular for soft-tissue reconstructions in
      nearly all regions of the body, the systematic application of perforator flaps
      with short, small-caliber pedicles for intraoral reconstruction has not been
      reported. Experience with the use of 10 consecutive perforator flaps from the
      lateral lower leg for intraoral defect coverage is reported. In 10 cases, a 4- to
      6-cm-long septocutaneous or myocutaneous perforating vessel from the peroneal
      artery, with a diameter of 1 to 2 mm, could be identified in the proximal one
      half of the lateral lower leg. The thin, pliable skin paddles, measuring up to 6
      x 8 cm, were used for defect coverage after resection of squamous cell carcinomas
      of the floor of the mouth (five cases), soft palate (one case), tongue (two
      cases), or buccal mucosa (two cases). Anastomoses were performed to the lingual
      artery and concomitant vein. Except for one case, all perforator flaps healed
      without complications and the functional results were satisfying. At the donor
      site, which was always closed directly, an approximately 15-cm-long scar
      resulted, without functional impairments. The peroneal artery was regularly
      preserved. Perforator flaps from the lateral lower leg might have many
      applications for intraoral soft-tissue reconstruction, especially because of
      their minimal donor-site morbidity.

PMID- 14707627
TI  - Sequential vascularized iliac bone graft and a superficial circumflex iliac
      artery perforator flap with a single source vessel for established mandibular
      defects.
AB  - The major problems in dealing with established mandibular loss are severe soft
      tissue contracture and a limited number of recipient vessels. The skin portion of
      the iliac osteocutaneous flap often necrotizes in cases without perforators of
      the deep circumflex iliac vessel. To overcome these problems, eight patients with
      established mandibular loss and no skin perforators of the deep circumflex iliac
      vessel were treated with a sequential vascularized iliac bone graft and a
      superficial circumflex iliac perforator flap with a single recipient vessel.
      Regarding the recipient vessels, the ipsilateral cervical vessels were used for
      four patients, and the contralateral facial and ipsilateral superficial temporal
      vessels were used for two cases each. The superficial circumflex iliac perforator
      flaps were 7 to 28 cm in length and 3 to 15 cm in width. The iliac bone grafts
      ranged from 7 to 13 cm in length, and three cases were repaired with the inner
      cortex of the iliac bone. There were no serious complications, such as flap
      necrosis or bone infection and resulting absorption. The advantages of this
      method are that both pedicles are very close to each other and of suitable
      diameter for anastomosis. Simultaneous flap elevation and preparation for the
      recipient site is possible. The skin flap and vascularized bone graft can be
      obtained from the same donor site. A single source vessel can nourish both the
      large skin area and bone sequentially. Longer dissection of the superficial
      circumflex iliac system to the proximal femoral division is unnecessary. A large
      flap can survive with a short segment of the superficial circumflex iliac system.
      Only the vascularized inner cortex of the iliac bone needs to be used, and the
      outer iliac cortex can be preserved, which results in less morbidity at the donor
      site.

PMID- 14707629
TI  - Objective assessment of speech after surgical treatment for oral cancer:
      experience from 196 selected cases.
AB  - In 1992, a personal computer-based workstation for speech-digitized analysis was
      developed in conjunction with Canniesburn Hospital and Edinburgh University to
      measure all dispersion in speech after surgery for oral cancer. The voices of 196
      patients with tumor of the oral cavity were recorded preoperatively and
      postoperatively. Surgical resection was carefully mapped out on standard diagrams
      of the oral cavity. Patients' recordings were assessed for conversational
      understandability by two referees. Patients also self-scored their speech using
      the Functional Intraoral Glasgow Scale self-questionnaire. Many patients had
      similar if not identical resections; therefore, 12 homogeneous groups were
      identified. Functional outcome for speech was correlated with the site and size
      of resected tissue and with the reconstruction modalities. The original
      association of an objective, computer-based tool and two subjective assessment
      tools proved to be the most suitable investigation method for speech. The general
      pattern was for consistently better speech quality with smaller excisions. The
      reconstruction modalities did not seem to influence the overall speech quality,
      as it was related mainly to the extent of surgical demolition. The authors
      present a detailed correlation between site and size of excision and functional
      outcome using color multiple-view diagrams for immediate appreciation. Positive
      and negative prognostic factors were identified in surgery for oral cancer.

PMID- 14707630
TI  - Free proximal gracilis muscle and its skin paddle compound flap transplantation
      for complex facial paralysis.
AB  - Gracilis functioning free-muscle transplantation for the correction of pure
      facial paralysis has been a preferred method used by many reconstructive
      microsurgeons. However, for complex facial paralysis, the deficits include facial
      paralysis along with soft-tissue, mucosa, and/or skin defects. No adequate
      solution has been proposed. Treatment requests in those patients are not only for
      facial reanimation but also for correction of the defects. Of 161 patients with
      facial paralysis treated with gracilis functioning free-muscle transplantation
      from 1986 to 2002, eight patients (5 percent) presented with complex deficits
      requiring not only facial reanimation but also aesthetic correction of tissue
      defects. The tissue defects included an intraoral defect created following
      contracture release (one patient), infra-auricular radiation dermatitis with
      contour depression (one patient), temporal depression following a temporalis
      muscle-fascia transfer (one patient), ear deformity (two patients), and infra
      auricular atrophic tissue with contour depression (three patients). A compound
      flap, consisting of a gracilis muscle with its overlying skin paddle separated
      into two components, was transferred for simultaneous correction of both
      problems. The blood supply to the gracilis and to the skin paddle originated from
      the same source vessel and therefore required the anastomosis of only one set of
      vessels. The versatility of this compound flap allows for a wide arc of rotation
      of the skin paddle around the muscle. All flaps were transferred successfully
      without complications. Satisfactory results of facial reanimation were recorded
      in five patients after all stages were completed. The remaining three patients
      are undergoing physical therapy and waiting for revision of the skin paddle.

PMID- 14707631
TI  - Comparison of unipedicled and bipedicled TRAM flap breast reconstructions:
      assessment of physical function and patient satisfaction.
AB  - Many variations of the transverse rectus abdominis musculocutaneous (TRAM) flap
      breast reconstruction have been attempted since the procedure was first
      described. One common modification involves the use of both rectus muscles, which
      may accommodate a bilateral reconstruction or provide a more reliable blood
      supply to a unilateral reconstruction. Objective studies measuring various
      aspects of physical strength after bilateral rectus harvest and subjective
      reports of various physical symptoms have challenged the morbidity of a double
      rectus harvest. Whether this represents increased morbidity in practical terms is
      best clarified by asking the patients. To answer this question, 124 TRAM flap
      reconstruction patients (62 unipedicled patients and 62 bipedicled patients)
      completed a survey containing questions regarding postoperative physical
      activities and abilities, outcome with regard to specific physical symptoms, and
      satisfaction with the procedure. The overwhelming majority of patients reported
      no untoward effect postoperatively regarding the following: workday performance
      (>or=90 percent), workday performance involving physical labor (>or=78 percent),
      physical recreation (>or=77 percent), abdominal appearance (>or=77 percent),
      standing posture (>or=95 percent), and back pain (>or=81 percent). When comparing
      unipedicled and bipedicled TRAM patient groups, there was no statistically
      significant difference between the two groups for any of these criteria. However,
      a subjective decrease in abdominal muscle strength was reported by 42 percent of
      unipedicled and 64 percent of bipedicled TRAM flap patients, and decreased
      abdominal muscle strength was the most frequently cited reason for
      dissatisfaction. Interestingly, this decreased strength did not affect the daily
      activities of the majority of patients, who were happy with the procedure (96
      percent) and would recommend it to others (96 percent).

PMID- 14707632
TI  - Investigation of TRAM flap oxygenation and perfusion by near-infrared reflection
      spectroscopy and color-coded duplex sonography.
AB  - Near-infrared reflection spectroscopy, used experimentally for investigation of
      tissue hemoglobin content and oxygenation in various flaps, was tested in the
      pedicled transverse rectus abdominis musculocutaneous (TRAM) flap, chosen as a
      simple clinical model because of its well-known vascular anatomy and clinical
      relevance. The study intended to answer the following questions: Does the near
      infrared reflection spectroscopy system used in this study measure tissue
      hemoglobin content and oxygenation in the superficial skin layers only, as
      proposed by the manufacturer? Is near-infrared reflection spectroscopy able to
      detect differences of tissue hemoglobin content and oxygenation in distinct zones
      of the TRAM flap skin before, early, and late after surgery? Does tissue
      hemoglobin content and oxygenation correspond to blood flow in the supplying
      superior epigastric artery and to clinical signs of TRAM flap perfusion and
      viability? In 11 patients, tissue hemoglobin content and oxygenation in the lower
      abdomen/TRAM flap, mastectomy skin flap, and contralateral breast were measured
      by a new near-infrared reflection spectroscopy system preoperatively, early
      postoperatively, and late postoperatively. Simultaneously, systolic peak flow in
      the ipsilateral superior epigastric artery was obtained by color-coded duplex
      sonography. Routine clinical monitoring was performed throughout the early
      postoperative period. Tissue hemoglobin content and oxygenation in the lower
      abdomen, mastectomy skin flap, and contralateral breast were similar before
      surgery but varied considerably between different patients. There were no
      significant differences among preoperative, early postoperative, and late
      postoperative values of tissue hemoglobin content and oxygenation in the
      mastectomy skin flap and contralateral breast. However, near-infrared reflection
      spectroscopy measurements of the TRAM flap revealed significant differences
      between preoperative and early postoperative values of tissue hemoglobin content
      and oxygenation and among zones I, II, and III early after surgery. Tissue
      hemoglobin content in the TRAM flap skin increased and oxygenation decreased
      early after surgery. Near-infrared reflection spectroscopy values corresponded to
      clinical signs of venous congestion predominantly in zone III. Late postoperative
      return of hemoglobin content and oxygenation in the TRAM flap toward preoperative
      values can be attributed to improved venous return by reversed flow across
      regurgitant valves and development of collateral circulation. Finally, there was
      a significant increase of systolic peak flow in the ipsilateral superior
      epigastric artery early after surgery. This could be related to the opening of
      small-caliber choke arteries between the superior and deep inferior epigastric
      arteries following ligation of the dominant deep inferior epigastric artery and
      TRAM flap transfer to the chest. Systolic peak flow returned to preoperative
      values late after surgery. The near-infrared reflection spectroscopy system used
      in this study appeared to measure hemoglobin content and oxygenation in the
      superficial skin layers only. Near-infrared reflection spectroscopy was able to
      detect differences of tissue hemoglobin content and oxygenation in the TRAM flap
      between preoperative and postoperative measurements and between distinct zones of
      the TRAM flap early postoperatively. Postoperative changes in near-infrared
      reflection spectroscopy values corresponded to clinical observations and blood
      flow in the superior epigastric artery measured by color-coded duplex sonography.
      Further experience is needed before near-infrared reflection spectroscopy can be
      advocated for routine clinical flap monitoring.

PMID- 14707633
TI  - Electromyographic assessment of rectus abdominis muscle function after deep
      inferior epigastric perforator flap surgery.
AB  - SUMMARY: The authors evaluated rectus abdominis muscle function after deep
      inferior epigastric perforator (DIEP) flap elevation. Fifteen consecutive
      patients who were operated on for breast reconstruction with a free DIEP flap
      were included in the study. A turn-amplitude electromyographic analysis was used.
      For each patient, the muscle activity was recorded in the portion of the muscle
      that was split for the epigastric perforator vessel dissection, and also in the
      similar portion of the contralateral nondissected muscle. A first
      electromyographic examination was carried out soon after surgery (mean follow-up,
      9 weeks), and a second electromyographic examination was carried out at a later
      date (mean follow-up, 15 months). The mean activity of the dissected muscles was
      50 percent of the activity of the nondissected muscles at the first
      electromyographic examination and 70 percent at the second electromyographic
      examination. The authors suggest that the DIEP flap procedure induces a partial
      denervation of the rectus abdominis muscle in the area of dissection and that
      reinnervation occurs over time because the entire width of the muscle and
      sufficient segmental motor innervation are preserved.

PMID- 14707634
TI  - Simplifying the vertical reduction mammaplasty.
AB  - The vertical reduction mammaplasty is an evolving technique. Its proponents
      report significantly decreased scarring, better breast shape, and more stable
      results compared with the standard inverted-T method, but the learning curve is
      long and cosmetic outcomes can be inconsistent. Many surgeons have experimented
      with the vertical closure before returning to methods more familiar to them. The
      authors present their modifications to the vertical reduction mammaplasty. Their
      changes simplify the preoperative markings and the intraoperative technique to
      shorten the learning curve while maintaining reliable aesthetic results. With the
      patient standing, only four preoperative marks are made: (1) the inframammary
      fold; (2) the breast axis; (3) the apex of the new nipple-areola complex; and (4)
      the medial and lateral limbs of the vertical incision. In the operating room, a
      medial or a superomedial pedicle is developed. Excess breast skin is resected
      with the inferior and lateral parenchyma as a C-shaped wedge. The lateral skin
      adipose flap is redraped inferomedially and sutured to the chest wall. The
      inferior aspect of the breast is aggressively debulked and a gathering
      subcuticular stitch is started 2 cm below the nadir of the nipple-areola complex.
      Finally, a 38-mm to 42-mm nipple-areola complex marker is used to create a
      circular defect that is offset 0.5 cm medial to the vertical axis of the breast.
      In their series, 56 patients were treated and no major complications were noted.
      The median follow-up period was 17 months. The average reduction was 554.5 g per
      breast; however, the reduction was greater than 1000 g per breast in eight
      patients. The authors found that (1) chest wall anchoring improves lateral
      contour and minimizes axillary fullness; (2) aggressive debulking inferiorly
      avoids the persistent inferior bulge; and (3) starting the subcuticular gathering
      suture 2 cm below the nipple-areola complex followed by placement of a nipple
      areola complex marker at the conclusion of the case prevents lateral deviation
      and corrects the nipple-areola complex teardrop deformity. These innovations
      accelerate the learning curve by simplifying the preoperative markings and lead
      to more consistent postoperative results and an improved cosmetic outcome. In
      conclusion, these modifications yield a simple, easily learned vertical reduction
      mammaplasty with aesthetically reliable results.

PMID- 14707635
TI  - Subglandular breast reduction: the evolution of a minimal scar approach to breast
      reduction.
AB  - The authors describe a new modification of the breast reduction procedure. By
      means of an inframammary incision, the breast is mobilized from the chest wall,
      and a "doughnut" annulus of breast tissue is removed from the undersurface of the
      gland. No skin is excised. The nipple-areola complex is left attached to a
      central core of breast tissue that receives its blood supply from the subdermal
      plexus of vessels. When the resulting defect is closed within the breast by
      strategically placed sutures, the base of the gland is narrowed, the breast is
      projected forward, and the circumareolar and vertical scars of other techniques
      are eliminated. The authors report their results in a series of 37 patients.

PMID- 14707636
TI  - Free split-cutaneous perforator flaps procured using a three-dimensional harvest
      technique for the reconstruction of postburn contracture defects.
AB  - With recent advances in free-tissue transfer, microsurgical techniques have been
      used more frequently for the reconstruction of postburn contracture defects.
      Traditional methods, including full-thickness skin grafts and local flaps, often
      result in a good outcome; however, multiple operative procedures, long periods of
      splinting, and physical rehabilitation are often required. Free split-cutaneous
      perforator flaps, consisting of one large cutaneous paddle with two perforating
      vessels split into two separate skin regions, were used for two kinds of postburn
      contractures: rectangular and spatially separate defects. From September of 2000
      to October of 2002, seven patients underwent this method of reconstruction at
      Chang Gung Memorial Hospital in Taiwan. A three-dimensional flap harvest method,
      in which the skin paddle is circumferentially elevated early in the harvest, was
      used. Postburn scar contractures had resulted from flame burns in six cases and
      an electric burn in one case. The reconstructive regions included the neck in two
      patients, the breast in one patient, and the hand in four patients. There were
      six male patients and one female patient, with a mean age of 34.8 years (range,
      25 to 49 years). The size of the excised scar ranged from 120 cm2 to 308 cm2
      (mean, 162.3 cm2). The size of the unsplit flaps ranged from 144 cm2 to 337.5 cm2
      (mean, 192.1 cm2). The average time for flap harvest using this three-dimensional
      harvest technique was 39.1 minutes. The average total operative time was 4.3
      hours. The average total hospital stay was 7.3 days (range, 6 to 11 days). All
      flaps survived without major complications. The donor site was closed primarily
      in all cases. At a mean follow-up time of 9 months, the functional and aesthetic
      outcomes showed significant improvement as compared with the preoperative
      condition. In this study, a new method of flap harvest using a three-dimensional
      technique is introduced, and its application in the reconstruction of postburn
      contractures is evaluated.

PMID- 14707637
TI  - Verifying surgical results and risk factors of the lateral thoracodorsal flap.
AB  - In 1986, the combined use of the lateral thoracodorsal flap and an implant was
      introduced as an alternative method of delayed reconstruction of small to medium
      size breasts for postmastectomy patients who are reluctant or unable to consider
      reconstruction by tissue expansion or by more extensive autologous tissue
      transplantation. So far, the technique has only been proven reproducible in
      Sweden. Postmastectomy radiotherapy has been proven to increase the risk of wound
      healing complications after lateral thoracodorsal transplantation, and additional
      risk factors such as advanced age, obesity, smoking, and some general health
      characteristics have been indicated. The authors initiated a prospective study to
      assess the reproducibility of this technique outside Sweden and to confirm the
      proven risk factor, prove or refute the alleged ones, and possibly identify
      additional factors. Additionally, they applied the technique for immediate breast
      reconstruction and tried to expand the indications and applications of the
      lateral thoracodorsal flap even further. The authors report on their initial
      experience with 60 lateral thoracodorsal flaps and conclude that the use of this
      flap is a well-reproducible technique for breast reconstruction, with few
      complications leading to failure. Using the lateral thoracodorsal flap in
      combination with tissue expanders allows for reconstruction of breasts of larger
      than medium size. Moreover, the authors successfully applied fully
      deepithelialized lateral thoracodorsal flaps for additional indications. The
      statistical significance of postmastectomy radiotherapy as a risk factor could
      not be confirmed, but some general health characteristics were found to be
      significant patient-related risk factors. Out of five procedure-related
      characteristics, only increased flap length was proven to negatively influence
      the outcome of the procedure.

PMID- 14707638
TI  - Treatment of massive thoracolumbar wounds and vertebral osteomyelitis following
      scoliosis surgery.
AB  - Closure of thoracolumbar wounds and vertebral osteomyelitis after scoliosis
      surgery often proves difficult due to tautness and lack of usable tissue, and the
      resulting dead space containing metallic fixation devices is predisposed to
      infections and complications. The authors present their experience with 33
      patients in whom massive thoracolumbar wounds and vertebral osteomyelitis
      developed following scoliosis surgery. Postoperative infection, due to the lack
      of vascularized tissue and presence of metallic hardware near the wound, is
      common and extremely counterproductive; within these cavernous wounds lie
      infected vertebrae, metallic hardware, and bone graft. The use of a modified and
      extended latissimus dorsi myocutaneous flap to close and supply blood to wounds
      in the lower thoracic and thoracolumbar areas is described. This surgical
      approach, predicated on effective debridement along with reconstruction by
      transposition of vascularized tissue, allows the wound to close and drastically
      decreases the risk of postoperative infection. Furthermore, for wounds already
      infected, the procedure allows for closure and increased blood supply to the
      area, thus giving the wound a much greater ability to heal. For wounds involving
      the lumbosacral area, the authors combine this with a transposed gluteus maximus
      muscle flap to obtain coverage over the caudal extent of the wound. In this
      study, all flaps accomplished their intended purpose: to secure the healing of
      once-infected wounds and to allow preservation of orthopedic instrumentation and
      bone graft. Follow-up revealed no flap losses, pseudarthroses, or loss of
      orthopedic instrumentation in the study group.

PMID- 14707639
TI  - Anatomical variations of the extensor tendons to the fingers over the dorsum of
      the hand: a study of 50 hands and a review of the literature.
AB  - The extensor tendons to the fingers were studied in dissections of 50 fresh
      cadaveric hands, and the divisions of the tendons, as well as the communications
      (juncturae), were analyzed. The pattern of distribution most frequently observed
      was as follows. The extensor digitorum communis provided one tendon to the index
      finger, one to the middle finger, two to the ring finger, and none to the little
      finger. The extensor indicis exhibited one tendon, whereas the extensor digiti
      minimi exhibited two tendons. The extensor indicis tendon was always observed to
      lack a junctura tendinum. The extensor indicis was absent in both hands of one
      cadaver. A tendon slip from the extensor digiti minimi to the ring finger was
      observed in one hand. All surgeons must bear in mind the existence of these
      variations when performing common tendon transfers.

PMID- 14707640
TI  - Soft-tissue sarcomas of the upper extremity: surgical treatment and outcome.
AB  - The objective of this retrospective follow-up study was to evaluate the outcome
      of patients with soft-tissue sarcoma treated by the authors' protocol, which
      consists of a selective combination of conservative surgery and radiotherapy.
      Patients who relapsed were especially evaluated to improve treatment results. The
      authors examined 80 patients with local soft-tissue sarcoma in the upper
      extremity referred to their multidisciplinary group. Fifteen patients were
      referred for first or subsequent local recurrence, and 65 patients were treated
      for primary tumor. The goal of treatment was local control and preservation of a
      functional limb. Wide excision was attempted. If the margin was less than 2.5 cm,
      postoperative radiotherapy was administered. Eighty-five percent of the patients
      were treated by limb salvage. Thirty patients needed reconstructive procedures
      such as pedicled (20 patients) or free flaps (10 patients). No free flaps were
      lost. The 5-year disease-specific overall survival rate was 75 percent, the local
      recurrence-free survival rate was 79 percent, and the metastasis-free survival
      rate was 68 percent. In univariate analysis, prognostic factors for local
      recurrence were extracompartmental site; for development of metastases, large
      size and extracompartmental site; and for decreased disease-specific overall
      survival, large size and extracompartmental site. Intramuscular, cutaneous, and
      subcutaneous tumors had a 5-year local control rate of 100 percent, and
      extracompartmental tumors had a local control rate of 69 percent.
      Extracompartmental tumors clearly have the worst prognosis and should be the main
      target for improving treatment strategies. After exclusion of patients with
      inadequate treatment according to the authors' protocol, the local control rate
      at 5 years was 90 percent. Strict adherence to treatment protocol should be
      practiced.

PMID- 14707641
TI  - Superficial circumflex iliac artery perforator flap for reconstruction of limb
      defects.
AB  - The superficial circumflex iliac artery perforator (SCIP) flap differs from the
      established groin flap in that it is nourished by only a perforator of the
      superficial circumflex iliac system and has a short segment (3 to 4 cm in length)
      of this vascular system. Three cases in which free superficial circumflex iliac
      artery perforator flaps were successfully transferred for coverage of soft-tissue
      defects in the limb are described in this article. The advantages of this flap
      are as follows: no need for deeper and longer dissection for the pedicle vessel,
      a shorter flap elevation time, possible thinning of the flap with primary
      defatting, the possibility of an adiposal flap with customized thickness for
      tissue augmentation, a concealed donor site, minimal donor-site morbidity, and
      the availability of a large cutaneous vein as a venous drainage system. The
      disadvantages are the need for dissection for a smaller perforator and an
      anastomosing technique for small-caliber vessels of less than 1.0 mm.

PMID- 14707642
TI  - Preoperative color Doppler assessment in planning of anterolateral thigh flaps.
AB  - The anterolateral thigh flap has many advantages, but it has not yet achieved
      widespread use because the perforators exhibit considerable anatomical variation
      and their locations are difficult to predict preoperatively. The authors
      performed a prospective study to investigate whether acoustic Doppler flowmetry
      and color Doppler ultrasonography were helpful for preoperative localization of
      the perforators in anterolateral thigh flaps. Ten patients scheduled for
      anterolateral thigh flap surgery were examined preoperatively with both acoustic
      Doppler flowmetry and color Doppler ultrasonography, and all points where the
      perforators seemed to penetrate the fascia lata were mapped. The actual
      perforating points were identified intraoperatively and were compared with the
      preoperatively mapped points. Fifteen perforators were detected in 10 patients.
      The concordance rate with acoustic Doppler flowmetry was 40 percent (95 percent
      confidence interval, 15 to 68 percent; p = 0.05). In contrast, the concordance
      rate with color Doppler ultrasonography was 100 percent (95 percent confidence
      interval, 81 to 100 percent; p = 0.05). Color Doppler examination was
      significantly more accurate than acoustic Doppler examination (determined by the
      binomial test; p < 0.0014). Three-dimensional anatomical information around the
      perforators was further useful in elevating flaps. The authors conclude that
      color Doppler examination can accurately identify the perforators and is useful
      for planning in anterolateral thigh flap surgery, whereas acoustic Doppler
      examination is unreliable.

PMID- 14707643
TI  - Fingertip replantation using the subdermal pocket procedure.
AB  - Restoration of finger length and function are the goals of replantation after
      fingertip amputation. Methods include microsurgical replantation and
      nonmicrosurgical replantation, such as composite graft techniques. To increase
      the survival rates for composite grafts, the subcutaneous pocket procedure has
      been used as a salvage procedure. The subdermal pocket procedure, which is a
      modification of the subcutaneous pocket procedure, was used for replantation of
      17 fingertips in 16 consecutive patients. Eight fingertips experienced guillotine
      injuries and the other nine fingertips experienced crush injuries.
      Revascularization of one digital artery without available venous outflow was
      performed for six fingers, and composite graft techniques were used for the other
      11 fingers. The success rate was 16 of 17 cases. The difference in success rates
      for guillotine versus crush injuries was statistically significant. Comparison of
      patients with arterial anastomoses and patients without arterial anastomoses also
      indicated a statistically significant difference. Thirteen fingertips survived
      completely. One finger, demonstrating complete loss and early termination of the
      pocketing procedure, was amputated on the eighth postoperative day. Two fingers
      were partially lost because of severe crushing injuries. One finger demonstrated
      partial loss of more than one quarter of the fingertip, which required secondary
      revision, because the patient was a heavy smoker. The pocketing period was 8 +/-
      1 days (mean +/- SD, n = 6) for the fingers revascularized with one digital
      arterial anastomosis and 13.3 +/- 1.9 days (n = 10) for the fingers successfully
      replanted with composite graft techniques. The mean active range of motion of the
      interphalangeal joint of the three thumbs was 65 +/- 5 degrees, and that of the
      distal interphalangeal joint of the other 11 fingers was 51 +/- 11 degrees. The
      static two-point discrimination result was 6.4 +/- 1.0 mm (n = 14) after an
      average of 11 +/- 5 months of follow-up monitoring. Compared with other methods,
      the subdermal pocket procedure has the advantages of exact subdermal/subdermal
      contact, a shorter pocketing period, and more feasible observation. The method
      can offer an alternative salvage procedure for fingertip amputations with no
      suitable vessels available for microsurgical replantation.

PMID- 14707644
TI  - Relaxation incision and fascia lata grafting in the surgical correction of penile
      curvature in Peyronie's disease.
AB  - The purpose of this study was to evaluate the effects of treatment of curvature
      in Peyronie's disease with a relaxation incision and fascia lata grafting.
      Between 2000 and 2002, this technique was used for 12 patients with a 1-year
      history of plaque and curvature of more than 35 degrees. Penile degloving was
      performed with a circumferential incision. The tunica defect was closed with
      fascia lata grafting after a relaxation incision. For all patients, penile
      curvature was corrected and normal erections were achieved. No complication was
      observed in 9 to 24 months (mean, 10 months) of follow-up monitoring. The initial
      results suggested that tunica albuginea incision and fascia lata grafting could
      represent an alternative for the treatment of curvature in Peyronie's disease.
      Further studies are warranted.

PMID- 14707645
TI  - New murine model of spontaneous autologous tissue engineering, combining an
      arteriovenous pedicle with matrix materials.
AB  - The authors previously described a model of tissue engineering in rats that
      involves the insertion of a vascular pedicle and matrix material into a semirigid
      closed chamber, which is buried subcutaneously. The purpose of this study was to
      develop a comparable model in mice, which could enable genetic mutants to be used
      to more extensively study the mechanisms of the angiogenesis, matrix production,
      and cellular migration and differentiation that occur in these models. A model
      that involves placing a split silicone tube around blood vessels in the mouse
      groin was developed and was demonstrated to successfully induce the formation of
      new vascularized tissue. Two vessel configurations, namely, a flow-through
      pedicle (n = 18 for three time points) and a ligated vascular pedicle (n = 18),
      were compared. The suitability of chambers constructed from either polycarbonate
      or silicone and the effects of incorporating either Matrigel equivalent (n = 18)
      or poly(DL-lactic-co-glycolic acid) (n = 18) on angiogenesis and tissue
      production were also tested. Empty chambers, chambers with vessels only, and
      chambers with matrix only served as control chambers. The results demonstrated
      that a flow-through type of vascular pedicle, rather than a ligated pedicle, was
      more reliable in terms of patency, angiogenesis, and tissue production, as were
      silicone chambers, compared with polycarbonate chambers. Marked angiogenesis
      occurred with both types of extracellular matrix scaffolds, and there was
      evidence that native cells could migrate into and survive within the added
      matrix, generating a vascularized three-dimensional construct. When Matrigel was
      used as the matrix, the chambers filled with adipose tissue, creating a highly
      vascularized fat flap. In some cases, new breast-like acini and duct tissue
      appeared within the fat. When poly(dl-lactic-co-glycolic acid) was used, the
      chambers filled with granulation and fibrous tissue but no fat or breast tissue
      was observed. No significant amount of tissue was generated in the control
      chambers. Operative times were short (25 minutes), and two chambers could be
      inserted into each mouse. In summary, the authors have developed an in vivo
      murine model for studying angiogenesis and tissue-engineering applications that
      is technically simple and quick to establish, has a high patency rate, and is
      well tolerated by the animals.

PMID- 14707646
TI  - Prolongation of skin allograft survival after neonatal injection of donor bone
      marrow and epidermal cells.
AB  - Composite-tissue (e.g., hand allograft) allotransplantation is currently limited
      by the need for immunosuppression to prevent graft rejection. Inducing a state of
      tolerance in the recipient could potentially eliminate the need for
      immunosuppression but requires reprogramming of the immunological repertoire of
      the recipient. Skin is the most antigenic tissue in the body and is consistently
      refractory to tolerance induction regimens using bone marrow transplantation
      alone. It was hypothesized that tolerance to skin allografts could be induced in
      rats by injecting epidermal cells with bone marrow cells during the first 24
      hours of life of the recipients. Brown Norway rats (RT1n) served as donors for
      the epidermal cells, bone marrow cells, and skin grafts. Epidermal cells were
      injected intraperitoneally and bone marrow cells were injected intravenously into
      Lewis (RT1l) newborn recipient rats. In control groups, recipients received
      saline solution with no cells (group I, n = 12), bone marrow cells only (group
      II, n = 15), or epidermal cells only (group III, n = 15). In the experimental
      group (group IV, n = 18), recipients received epidermal and bone marrow cells
      simultaneously. Skin grafts were transplanted from Brown Norway (RT1n) rats to
      the Lewis (RT1l) rats 8 weeks after cell injections. Skin grafts survived an
      average of 8.5 days in group I (10 grafts), 9.2 days in group II (12 grafts), and
      12 days in group III (14 grafts). Grafts survived 15.5 days (8 to 26 days) in
      group IV (15 grafts). The difference was statistically significant (p < 0.05).
      Hair growth was observed in some accepted grafts in group IV but never in the
      control groups. This is the first report of prolonged survival of skin allografts
      in a rat model after epidermal and bone marrow cell injections. Survival
      prolongation was achieved across a major immunological barrier, without
      irradiation, myeloablation, or immunosuppression. It is concluded that the
      presentation of skin-specific antigens generated a temporary state of tolerance
      to the skin in the recipients that could have delayed the rejection of skin
      allografts.

PMID- 14707647
TI  - Comparison of three different supercharging procedures in a rat skin flap model.
AB  - A significant clinical problem in reconstructive surgery is partial loss of a
      pedicled flap. To resolve this problem, various methods of vascular augmentation
      have been developed; "supercharging" is one of those techniques. A new rat flap
      model was developed for investigation of the supercharging procedure, and the
      efficacy of the arterial supercharging method was examined. The purpose of this
      study was to investigate how an arterial supercharging procedure could generate
      large flap survival areas with different supercharging positions in rats. On the
      basis of the vascular anatomical features of rats, a circumferential skin flap
      from the lower abdomen to the back, measuring 4 x 12 cm, was marked. The flap was
      divided along the dorsal midline. Forty rats were divided into four experimental
      groups, as follows: group 1 (control), flaps based only on the deep circumflex
      iliac artery and vein; group 2, flaps supercharged with the ipsilateral
      superficial inferior epigastric artery; group 3, flaps supercharged with the
      contralateral superficial inferior epigastric artery; group 4, flaps supercharged
      with the contralateral deep circumflex iliac artery. On the fourth postoperative
      day, the flaps were evaluated with measurements of necrosis and survival areas.
      Microfil (Flow Tech, Inc., Carver, Mass.) was then injected manually throughout
      the body, and the vascular changes produced by supercharging were
      angiographically evaluated. Compared with group 1 (control), the flap survival
      areas were significantly greater in distally supercharged flaps in groups 3 and 4
      (mean flap survival, 91.2 +/- 5.2 percent and 90.5 +/- 10.6 percent,
      respectively; p < 0.001) and in proximally supercharged flaps in group 2 (45.9 +/
      4.1 percent, p < 0.05). Angiographic assessment of the flaps that survived
      completely revealed marked dilation of the choke veins among the territories and
      reorientation of dilated veins along the axes of the flaps. This study suggests
      that distal arterial supercharging (contralateral superficial inferior epigastric
      artery or contralateral deep circumflex iliac artery) is more effective than
      proximal arterial supercharging (ipsilateral superficial inferior epigastric
      artery) in increasing flap survival. Although the rat skin flap may not be
      analogous to human flaps, distal arterial supercharging might have useful
      therapeutic potential in increasing flap survival in clinical practice.

PMID- 14707648
TI  - Selective recruitment of endothelial progenitor cells to ischemic tissues with
      increased neovascularization.
AB  - Tissue ischemia remains a common problem in plastic surgery and one for which
      proangiogenic approaches have been investigated. Given the recent discovery of
      circulating endothelial stem or progenitor cells that are able to form new blood
      vessels, the authors sought to determine whether these cells might selectively
      traffic to regions of tissue ischemia and induce neovascularization. Endothelial
      progenitor cells were isolated from the peripheral blood of healthy human
      volunteers and expanded ex vivo for 7 days. Elevation of a cranially based random
      pattern skin flap was performed in nude mice, after which they were injected with
      fluorescent-labeled endothelial progenitor cells (5 x 10(5); n = 15), fluorescent
      labeled human microvascular endothelial cells (5 x 10(5); n = 15), or media alone
      (n = 15). Histologic examination demonstrated that endothelial progenitor cells
      were recruited to ischemic tissue and first appeared by postoperative day 3.
      Subsequently, endothelial progenitor cell numbers increased exponentially over
      time for the remainder of the study [0 cells/mm2 at day 0 (n = 3), 9.6 +/- 0.9
      cells/mm2 at day 3 (n = 3), 24.6 +/- 1.5 cells/mm2 at day 7 (n = 3), and 196.3 +/
      9.6 cells/mm2 at day 14 (n = 9)]. At all time points, endothelial progenitor
      cells localized preferentially to ischemic tissue and healing wound edges, and
      were not observed in normal, uninjured tissues. Endothelial progenitor cell
      transplantation led to a statistically significant increase in vascular density
      in ischemic tissues by postoperative day 14 [28.7 +/- 1.2 in the endothelial
      progenitor cell group (n = 9) versus 18 +/- 1.1 in the control media group (n =
      9) and 17.7 +/- 1.0 in the human microvascular endothelial cell group (n = 9; p <
      0.01)]. Endothelial progenitor cell transplantation also showed trends toward
      increased flap survival [171.2 +/- 18 mm2 in the endothelial progenitor cell
      group (n = 12) versus 134.2 +/- 10 mm2 in the media group (n = 12) and 145.0 +/-
      13 mm2 in the human microvascular endothelial cell group (n = 12)], but this did
      not reach statistical significance. These findings indicate that local tissue
      ischemia is a potent stimulus for the recruitment of circulating endothelial
      progenitor cells. Systemic delivery of endothelial progenitor cells increased
      neovascularization and suggests that autologous endothelial progenitor cell
      transplantation may have a role in the salvage of ischemic tissue.

PMID- 14707649
TI  - Microvascular anastomosis in an optical cavity: is it possible?
AB  - Microsurgery is one of the highly interesting surgical procedures that can be
      performed using different applications and in different specialties, including
      plastic surgery. The endoscope is a popular instrument used in many fields,
      including plastic surgery. Although the operating microscope is still a must for
      microsurgical performance, microsurgery could be performed, depending on the
      experiences and facilities, by using other visual-assisting equipment. From this
      point of view, the authors tried to find less costly and more widespread
      equipment suitable for performing microsurgery that can, furthermore, be applied
      in special situations and indications, such as operating in an optical cavity.
      The authors investigated this issue with the endoscope. In this experimental
      project, the authors performed vascular microsurgical anastomoses of the rats'
      femoral vessels to create an optical cavity in a prefabricated skin retraction
      model in the groin area of 10 Sprague-Dawley male rats. The microsurgical
      anastomoses of the femoral vessels and nerves were performed easily in a
      reasonable time, without recorded difficulties, and with maximum physical and
      visual comfort for the surgeon. The authors spent a mean time of 28.1, 27.3, and
      19.2 minutes for the arterial, venous, and neural anastomoses, respectively. In
      this group of animals, 90 percent vascular patency and 100 percent accurate
      neural anastomoses were recorded. The advantage the authors noted was that this
      new technique of operating in the field of microsurgery, with its feasibility and
      difficulties, would be a point of research and application for the young
      generations of microsurgeons.

PMID- 14707650
TI  - Simultaneous correction of major hypertelorism, frontal bone defect, nasal
      aplasia, and cleft of the upper lip (Tessier 0-14).

PMID- 14707652
TI  - One-stage complete phalloplasty with forearm free flap after severe electrical
      burns.

PMID- 14707651
TI  - Calciphylaxis: medical and surgical management of chronic extensive wounds in a
      renal dialysis population.

PMID- 14707653
TI  - Extensive locoregional malignant melanoma transformation in a patient with
      oculodermal melanocytosis.

PMID- 14707654
TI  - Correction of eyebrow malposition in patients with traumatic injury using
      endoscopic forehead lift technique.

PMID- 14707655
TI  - Surgical correction of inverted nipples using the modified Namba or Teimourian
      technique.

PMID- 14707656
TI  - The conjoint medial circumflex femoral perforator and gracilis muscle free flap.

PMID- 14707657
TI  - Polytetrafluoroethylene facial implants: 15 years later.

PMID- 14707659
TI  - Validity of a structured method of selecting abstracts for a plastic surgical
      scientific meeting.
AB  - In 1999, the European Association of Plastic Surgeons accepted a structured
      method to assess and select the abstracts that are submitted for its yearly
      scientific meeting. The two criteria used to evaluate whether such a selection
      method is accurate were reliability and validity. The authors previously
      established this method to be reliable on the basis of a prospective evaluation
      of the selection process used for the 2000 meeting of the European Association of
      Plastic Surgeons. It is more difficult to assess the validity of this method
      because there is no objective standard of quality of a scientific abstract
      against which the accuracy of selection can be assessed. This study statistically
      evaluated the accuracy of the meeting participants' assessment of presentations
      made during the meeting as the criterion standard for abstract selection on the
      basis of data obtained from the 2002 selection process. The authors evaluated the
      interobserver repeatability among five meeting participants of selecting the best
      presentations, the validity of the method of abstract selection after this
      criterion standard had been established, and the validity of reviewers' rating of
      abstracts as indicators of the scientific value of the actual presentations. The
      authors conclude that the assessment of platform presentations at a plastic
      surgical meeting is reliable. Accepting this assessment as the criterion
      standard, however, they could not prove the validity of their selection method or
      the validity of the reviewers' rating of abstracts as an indicator of the
      scientific value of the actual presentations.

PMID- 14707658
TI  - An update on the timing of hard palate closure: a critical long-term analysis.

PMID- 14707660
TI  - Good to great.

PMID- 14707661
TI  - Treatment of human immunodeficiency virus-associated lipodystrophy with dermafat
      graft transfer to the malar area.
AB  - Acquired immunodeficiency syndrome, a death sentence two decades ago, has been
      transformed into a chronic disease with a life expectancy of many years, due to
      the advent of highly active antiretroviral therapy. Despite virologic success,
      nearly 50 percent of patients on highly active antiretroviral therapy develop
      lipodystrophy with central and visceral fat accumulation and/or facial and limb
      fat atrophy. The changes are referred to as the human immunodeficiency virus
      lipodystrophy syndrome. The authors describe a series of five patients with
      antiretroviral therapy-induced lipodystrophy of the face who benefited from
      surgical correction of their typical stigmatizing malar atrophy. Dermafat grafts
      were transferred from the abdominal wall to malar pockets through a transoral
      approach. The aesthetic results were dramatic and stable, lasting the duration of
      the 1- to 2-year follow-up period.

PMID- 14707662
TI  - Adipose compartments of the upper eyelid: anatomy applied to blepharoplasty.
AB  - Many authors have indicated the presence of ectopic or accessory upper eyelid fat
      pads, but the effective rate of eyelid fat variations and the corresponding
      clinical features are still unclear. The purpose of this study was to evaluate
      the variability of upper lid fat and to define the anatomical landmarks of the
      adipose pockets of the upper lid. From January of 1998 to January of 2002, the
      authors investigated the upper eyelid fat compartments of 47 patients who
      underwent upper blepharoplasty. To support surgical findings, 11 fresh cadavers
      were also investigated; the anatomy of the intraorbital fat and of the upper
      eyelid fat compartments was reviewed. Ten patients (21.3 percent) showed an
      accessory fat pad in the upper lid, which was found on both sides in nine cases.
      In all patients, the third fat pad was situated lateral to the two classic
      compartments described by Castanares, behind the orbital septum. Surgical
      dissections demonstrated that this fat pad derived from the preaponeurotic fat.
      Anatomical dissections in three cadavers demonstrated an accessory fat
      compartment protruding under the inferior border of the lacrimal gland. This
      protruding fat derived from the preaponeurotic fat in all cases and might justify
      the clinical appearance of a bulge or fullness in the lateral third of the upper
      eyelid. In the authors' experience, the presence of an accessory upper eyelid fat
      pad was a frequent finding during blepharoplasty; it could be found and actually
      resected in about 21 percent of all cases. Surgical and experimental findings put
      this element as a lateral physiological extension of the preaponeurotic fat that
      can anteriorly protrude under the inferior border of the lacrimal gland toward
      the orbital septum. The clinical appearance may be a bulge or fullness in the
      upper eyelid, and its resection can better define the lateral one third of the
      supratarsal fold.

PMID- 14707663
TI  - Avoiding hematoma in cervicofacial rhytidectomy: a personal 8-year quest.
      Reviewing 910 patients.
AB  - Hematoma remains the most common complication of rhytidectomy and can lead to
      prolonged facial edema and skin necrosis. A number of ancillary procedures have
      been suggested to reduce hematoma, including dressings, drains, fibrin glue,
      tumescence, and adrenaline. The aim of this study was to investigate the
      statistical effect of these parameters on hematoma incidence in a large series of
      face lifts. Over an initial 6-year period, 678 consecutive face lifts were
      performed and included in the first part of the study. The effect of dressings,
      drains, fibrin glue, and tumescence on hematoma rate was investigated
      retrospectively. In the second part of the study, the specific effect of
      adrenaline was analyzed while all other parameters were kept constant. The 229
      patients with adrenaline-containing infiltrations were compared with the 232
      patients whose infiltration had no adrenaline. Retrospective analysis of both
      groups was performed using Fisher's exact test. In the first part of the study
      investigating 678 consecutive face lifts, no difference in hematoma rate (4.4
      percent overall) was observed with the use of dressings (p > 0.5), drains (p >
      0.4), fibrin glue (p > 0.6), or tumescence (p > 0.5). In the second part of the
      study, the specific effect of withdrawing adrenaline in a comparative group of
      461 face lifts significantly reduced the incidence of hematoma requiring surgical
      evacuation (p < 0.0001). There was also a significant reduction in the incidence
      of minor hematoma requiring only aspiration (p = 0.02). There was no change in
      the incidence of any other face lift complications observed during this part of
      the study. This study found a significant reduction in the incidence of hematoma
      following face lifting. Although many of the suggested ancillary methods used to
      reduce hematoma did not produce any statistical reduction in the incidence of
      this complication, the exclusion of adrenaline had a profound effect. The
      technique and implications with respect to safety and outcome are described.

PMID- 14707664
TI  - In search of improved fat transfer viability: a quantitative analysis of the role
      of centrifugation and harvest site.
AB  - Fat grafting is an unpredictable procedure that continues to challenge the field
      of plastic surgery due to irregular resorption. Applications for this procedure
      are broad in both reconstructive and cosmetic plastic surgery. Fat grafts are
      carefully obtained and manipulated to obtain better graft takes and results, yet
      there is no universal agreement on what constitutes an ideal methodology. The
      present study examines adipocyte viability from four commonly used donor sites in
      five subjects. No statistical differences in adipocyte viability were
      demonstrated among abdominal fat, thigh fat, flank fat, or knee fat donor sites
      that were immediately removed and untreated (p < 0.225). In addition, no
      differences were observed in representative tissue samples that were removed and
      centrifuged (thigh, p = 0.508; knee, p = 0.302; flank, p = 0.088; abdomen, p =
      0.533). On the basis of these quantitative data, neither harvest location nor
      centrifugation demonstrated any advantage in terms of lipocyte viability. Fat
      tissue transfers from these common sites may be considered equal, and
      centrifugation does not appear to enhance immediate fat tissue viability before
      implantation.

PMID- 14707665
TI  - Reducing complications in cervicofacial rhytidectomy by tumescent infiltration: a
      comparative trial evaluating 678 consecutive face lifts.
AB  - Tumescent infiltration has been widely used in body-contouring surgery to
      facilitate dissection and reduce blood loss. Although its use in facial surgery
      has been suggested, there are presently no comparative studies of its efficacy.
      The aim of this study was to investigate the long-term outcome in a large series
      of consecutive face lifts performed with and without tumescence. During a 6-year
      period, 678 consecutive face lifts were performed: 449 without tumescence and 229
      with tumescent infiltration using 200 ml on each side of the face. The spectrum
      of techniques included the extended superficial musculoaponeurotic system (SMAS)
      procedure, the lateral SMASectomy, the extended supraplatysmal plane lift, and
      the cutaneous face lift. Complications, such as hematoma, skin necrosis,
      alopecia, and scar quality, were compared between groups using Fisher's exact
      test. The use of tumescent infiltration facilitated dissection, particularly in
      the neck. Postoperative swelling and bruising were reduced in the tumescent
      group. In comparisons of major complications between groups, no difference was
      seen in hematoma rate (p > 0.5), although the incidence of other complications
      was significantly reduced by tumescent infiltration. Significant reduction was
      observed in the rate of skin necrosis (p = 0.03), alopecia (p = 0.006),
      hypertrophic scarring (p = 0.001), stretched scarring (p = 0.003), and scar
      revision (p < 0.001). This is the first comparative study of tumescent
      infiltration in facial rejuvenation surgery. Tumescence made dissection easier
      and significantly reduced the incidence of troublesome complications. The
      surgical technique and aesthetic implications for rejuvenation surgery are
      discussed.

PMID- 14707666
TI  - A minimally invasive approach for correction of chin ptosis.
AB  - Although ptosis of the tip of the chin is common and can be seen in persons of
      any age, it is frequently seen in older patients seeking facial rejuvenation. A
      variety of techniques have been described to correct ptosis of the chin. The
      authors describe a minimally invasive method that can be used correct chin
      ptosis. This technique uses a small intraoral incision to place a U-shaped
      Prolene suture that gathers the soft tissue of the chin and elevates it above the
      lower border of the mandibular symphysis. A retrospective review of 314 cases
      performed in conjunction with face lifts between January of 1994 and January of
      2000 was performed to evaluate this technique. There were no significant
      complications, and long-term results have been very satisfactory and lasting.

PMID- 14707667
TI  - Maximizing the use of the abdominoplasty incision.
AB  - Candidates for abdominoplasty often request multiple procedures at the time of
      consultation. Some of these patients have the potential opportunity to have
      ancillary procedures performed through the abdominoplasty incision, such as
      breast augmentation or suction-assisted lipectomy. Access via the abdominoplasty
      incision can also limit the need for distant donor sites, for instance, when
      autologous fillers or rib graft are necessary. The techniques described are
      straightforward and are based on standard principles that should be considered
      when ancillary procedures are performed in conjunction with abdominal contouring
      procedures. In a review of 70 consecutive patients undergoing abdominoplasty, 91
      ancillary procedures were performed in conjunction with the abdominoplasty. Of
      the total number of patients undergoing abdominoplasty, 29 patients underwent 30
      procedures facilitated through their abdominoplasty incision, including 23
      suction-assisted lipectomies of the flanks, six breast augmentations, and one rib
      cartilage harvesting for rhinoplasty. A review of the author's experience and
      discussion for potential options afforded by this exposure are presented.

PMID- 14707668
TI  - Lipectomy of the ilio-lumbosacral region.
AB  - In the past, several techniques for raising the gluteal mass have been described,
      all of which were based on dermolipectomies of major or minor extension. The main
      disadvantage of these dermolipectomies is the visible external scar. The author
      presents his technique for lipectomy of the ilio-lumbosacral region. It is
      proposed that multiplanar liposuction in this region lengthens the lumbar
      lordotic curve and results in upward traction on the buttocks, resulting in a
      more youthful contour of the region. The article describes a series of 98
      patients with lipodystrophy of the ilio-lumbosacral area who underwent
      liposuction of the region and were highly satisfied with the results.

PMID- 14707669
TI  - Mandibular contouring surgery by angular contouring combined with genioplasty in
      orientals.

PMID- 14707670
TI  - Pain is only temporary, pride is forever.

PMID- 14707671
TI  - Humanitarian missions in the third world: a polite dissent.

PMID- 14707672
TI  - Reduction mammaplasty: the need for prospective randomized studies.

PMID- 14707673
TI  - Professor Ruyao Song, 1914 to 2003.

PMID- 14707675
TI  - Detection of subclinical infections in significant breast implant capsules.

PMID- 14707676
TI  - Frequently unrecognized causes of breast asymmetry.

PMID- 14707677
TI  - Use of available micromotor irrigation system for liposuction tumescent fluid
      infiltration.

PMID- 14707678
TI  - Monozygotic twins discordant for thumb polydactyly.

PMID- 14707679
TI  - Iliac bone grafts for orbital wall reconstruction.

PMID- 14707680
TI  - Avoiding tracheostomy: submental intubation in faciomaxillary trauma surgery.

PMID- 14707681
TI  - Free-tissue transfers with Varioscope: an alternative to microscope.

PMID- 14707682
TI  - Rhinoplasty in the African-American patient.

PMID- 14707683
TI  - Custom-made periareolar wavy-line marker.

PMID- 14707684
TI  - Estimation of the size of cutaneous lesions.

PMID- 14707685
TI  - Measurement of lymphedema using a simple device.

PMID- 14707686
TI  - A simple device for safe use of Kirschner wires.

PMID- 14707687
TI  - Plastic surgery: is extreme a dream or a nightmare?

PMID- 14707688
TI  - Electrocardiograph dot as a preoperative marker for nipple-areola complex
      reconstruction.

PMID- 14707689
TI  - A record of intraoperative findings in hand trauma.

PMID- 14707690
TI  - Don't try this at home: liposuction in the kitchen by an unqualified practitioner
      leads to disastrous complications.

PMID- 14707691
TI  - Risks associated with "components separation" for closure of complex abdominal
      wall defects.

PMID- 14707692
TI  - Skin hook and forceps as a unified instrument: the griffin forceps.

PMID- 14707693
TI  - The "deep pedicle" V-Y advancement flap.

PMID- 14707694
TI  - Treatment modalities using upper eyelid for full-thickness defects of lower lids:
      less morbidity and better results.

PMID- 14707695
TI  - "Meshing" a small skin graft.

PMID- 14707696
TI  - An easy and safe method to apply leeches on flaps: the leech cage.

PMID- 14707697
TI  - Skin ulcers after rhinoplasty in a patient with Behcet disease.

PMID- 14707698
TI  - The viability of autoclaved dysplastic bone graft.

PMID- 14707701
TI  - Late onset of clinical symptoms and recurrent ecchymotic skin lesions in a 12
      year-old girl with a severe double heterozygous protein C deficiency.
AB  - The authors describe a 12-year-old girl with late-onset clinical symptoms due to
      severe protein C deficiency. Protein C gene analysis showed double heterozygosity
      for two distinct mutations, associated with type I protein C deficiency. Her
      parents and only brother were also evaluated. Coumarin-induced skin necrosis was
      a recurrent feature during oral anticoagulation therapy, forcing her physicians
      to treat her with nadroparin (Fraxiparin) for only a few months.

PMID- 14707702
TI  - Osteoblast and osteoclast activity in a malignant infantile osteopetrosis patient
      following bone marrow transplantation.
AB  - The authors treated a 6-month-old boy with malignant infantile osteopetrosis
      using bone marrow transplantation. The patient's clinical response was compared
      with his biochemical response for bone metabolic markers such as tartrate
      resistant acid phosphatase 5b (TRAcP 5b) and bone-specific alkaline phosphatase
      (BAP). Treatment was successful, resulting in a decrease in the serum TRAcP 5b
      level. These bone-specific markers may be useful for the early assessment of
      malignant infantile osteopetrosis patients with stem cell transplantation.

PMID- 14707703
TI  - HIV infection presenting as severe autoimmune hemolytic anemia with disseminated
      intravascular coagulation in an infant.
AB  - Autoimmune hemolytic anemia is rare in children. It is generally diagnosed in
      relation to a viral or bacterial infection but has also been described in
      association with drugs, autoimmune disease, malignancy, and immunodeficiency. The
      authors describe a 5-month-old infant who presented with severe autoimmune
      hemolytic anemia and disseminated intravascular coagulation as his initial
      manifestation of HIV infection.

PMID- 14707704
TI  - Pancytopenia due to suppressed hematopoiesis in a case of fatal hemolytic disease
      of the newborn associated with anti-K supported by molecular K1 typing.
AB  - The authors report on a fatal case of hemolytic disease of the newborn (HDN) due
      to anti-K antibodies with subsequent trilineage pancytopenia in a preterm infant
      of 28 weeks gestational age, with pronounced leukopenia and neutropenia. In
      addition, molecular typing of the Kk polymorphism was necessary to confirm HDN.
      This case of HDN associated with anti-K provides additional evidence that
      trilineage pancytopenia due to suppressed hematopoiesis is part of the disease.
      Therefore, antibodies against antigens of the Kell blood group system should be
      considered as a potential cause of unexplained inhibition of myelopoiesis.

PMID- 14707705
TI  - Fatal hemorrhage from androgen-related hepatic adenoma after hematopoietic cell
      transplantation.
AB  - Fanconi anemia is a rare genetic disorder that leads to bone marrow failure.
      Hematopoietic cell transplantation (HCT) is currently the only treatment option
      with curative potential. When a suitable HLA-matched sibling donor is not
      available, patients are often treated with androgenic steroids before considering
      HCT. Such androgen treatments can lead to the development of hepatic adenomas,
      which usually regress upon stopping androgen therapy. A patient with Fanconi
      anemia is described who underwent an unrelated umbilical cord blood transplant
      with a history of a hepatic adenoma related to androgen therapy. No adenomas were
      detected on an ultrasound examination prior to HCT. Soon after HCT, he died due
      to sudden rupture and hemorrhage of a hepatic adenoma. This case illustrates the
      need for extra vigilance in the detection and management of hepatic adenomas in
      patients treated with androgens, especially prior to HCT.

PMID- 14707706
TI  - Extranodal Rosai-Dorfman disease in children.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease
      (RDD), is a histiocytic disorder that usually presents with painless massive
      cervical lymphadenopathy. The course is usually self-limited, but treatment may
      be required in cases with compression of vital organs. Patients may present with
      extranodal involvement only, and in these cases the clinical and histologic
      diagnosis may be difficult. The authors describe three patients with RDD who had
      exclusive extranodal disease in the head and neck area, in whom the clinical
      presentation mimicked other more common conditions.

PMID- 14707707
TI  - Activated protein C concentrate reverses purpura fulminans in severe genetic
      protein C deficiency.
AB  - Severe genetic protein C deficiency is rare and is associated with severe, often
      fatal thrombosis. The authors report the use of recombinant activated protein C
      (APC) to treat an episode of purpura fulminans (PF) in a teenage girl with severe
      protein C deficiency who had developed anaphylaxis to fresh-frozen plasma that
      was given in the past to treat recurrent episodes of PF. Concomitant with an
      infusion of APC, 20 microg/kg/h for 10 hours, a d-dimer level that was markedly
      positive (6,450 ng/mL) prior to the onset of PF decreased to 847 ng/mL following
      the APC. The teenager was treated with heparin along with warfarin for four days
      until the INR was more than 3.5 and the d-dimer level was less than 230 ng/mL. At
      the end of the APC infusion all skin lesions of PF were resolved. There were no
      adverse reactions to APC. APC was safe and effective for treatment of PF in
      severe genetic protein C deficiency.

PMID- 14707708
TI  - Intracranial meningeal extramedullary hematopoiesis inducing serious headache in
      a patient with idiopathic myelofibrosis.

PMID- 14707709
TI  - Leftward -alpha4.2 deletion alpha-thalassemia in a patient of northern European
      extraction.

PMID- 14707710
TI  - Approaches to treatment for extraocular retinoblastoma: Children's Hospital Los
      Angeles experience.
AB  - Extraocular retinoblastoma is associated with a very poor outcome. At Children's
      Hospital Los Angeles, 10 of 207 patients with retinoblastoma had extraocular
      disease. Four patients with no histopathologic risk factors developed extraocular
      disease. All patients with direct extension into the central nervous system or
      with distant metastatic disease died. One of three patients with trilateral
      retinoblastoma and one patient with regional recurrence are alive after
      autologous bone marrow transplant. Patients with extraocular retinoblastoma who
      achieve remission may benefit from consolidation of their therapy with autologous
      bone marrow transplant.

PMID- 14707711
TI  - Radically different treatment recommendations for newly diagnosed neuroblastoma:
      pitfalls in assessment of risk.
AB  - Neuroblastoma risk stratification is based on stage, age, and biology and
      prescribes surgery for low-risk disease, moderate-dose chemotherapy for
      intermediate-risk disease, and maximal therapy (including myeloablative treatment
      with stem cell transplantation) for high-risk disease. Four cases are described
      that depict pitfalls in risk assessment with potentially far-reaching
      consequences. This report focuses on a subset of four patients referred for
      second opinions. Stage was defined by the International Neuroblastoma Staging
      System. The first recommendations were for maximal therapy, but second opinions
      were radically different (ie, surgery alone). Ages at diagnosis were 15 to 25
      months. Shimada histopathology was unfavorable in three of the four patients, but
      chromosomal, serum, and urine prognostic markers were favorable. All four
      patients did well without cytotoxic therapy (follow-up: 2 years 10 months plus to
      4 years 8 months plus). Patient 1 had abdominal and upper
      thoracic/supraclavicular masses (stage 4); the former was resected and the latter
      spontaneously regressed. Patient 2 had retroperitoneal disease, without bone
      marrow involvement, but imaging studies showed lesions in vertebral bodies.
      Biopsies of the latter showed no neuroblastoma and the primary tumor (with
      regional lymph nodes) was resected, changing stage from 4 to 2B. Patient 3 had a
      retroperitoneal mass but no distant disease. Though initially deemed to be
      unresectable, the abdominal tumor was excised, changing the classification from
      high risk (stage 3 with unfavorable histopathology) to low risk (stage 1).
      Patient 4 had a pelvic mass, with unfavorable histopathology, and bilateral
      inguinal lymph node involvement (stage 3); all soft tissue disease was resected.
      The absence of cortical bone and extensive bone marrow metastatic involvement in
      a young neuroblastoma patient should cause a shift in attention to biologic
      prognostic markers. Some patients classified as having high-risk neuroblastoma
      might actually do well with no cytotoxic therapy.

PMID- 14707712
TI  - Molecular diagnosis of cerebral aspergillosis by sequence analysis with panfungal
      polymerase chain reaction.
AB  - The authors describe a patient with osteosarcoma in whom a brain abscess
      developed after autologous peripheral stem cell transplantation. Serologic
      markers of fungal infection were negative, but fungal DNA was detected in the
      cerebrospinal fluid (CSF) by panfungal polymerase chain reaction (PCR) assay
      using primers derived from fungal 18S ribosomal RNA (rRNA) genes. The sequence of
      PCR products on the panfungal assay was identical to the 18S rRNA genes of
      Aspergillus species. The combination of sequence analysis and panfungal PCR assay
      could be useful in the diagnosis of cerebral aspergillosis.

PMID- 14707713
TI  - Acute lymphocytic leukemia in a child with Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by
      neonatal hypoglycemia, abdominal wall defects, macroglossia, organomegaly, ear
      pits and creases, hemihypertrophy, and increased birthweight. Children with BWS
      have an increased risk of malignancy. The authors present the case of a 3-year
      old boy diagnosed with both BWS and acute lymphocytic leukemia (ALL). This case
      report will elaborate on the possibilities as to how BWS and ALL may be
      associated due to abnormal genomic imprinting and IGF dysregulation.

PMID- 14707714
TI  - A case of childhood peripheral T-cell lymphoma with massive cardiac infiltration.
AB  - ALK-negative CD30-negative peripheral T-cell lymphoma (PTCL) is an exceedingly
      rare neoplasm in children. Equally rare is the finding of cardiac involvement
      from lymphoma at presentation. The authors present a pediatric patient with PTCL
      involving the heart. The patient had orthopnea and an abnormal echocardiogram on
      presentation. After three doses of radiation, he died, and the autopsy showed
      massive infiltration of the heart and cardiac vessels by tumor. The authors
      review briefly the biology of PTCL and the incidence of cardiac involvement with
      lymphoma, which is not often appreciated prior to death.

PMID- 14707715
TI  - Medulloblastoma as a first presentation of fanconi anemia.
AB  - Fanconi anemia is a chromosomal instability syndrome associated with certain
      congenital abnormalities, defective hemopoiesis, and an increased risk of
      developing acute myeloid leukemia and some solid tumors. The diagnosis can be
      made at birth if congenital abnormalities are present but is often made in
      childhood when hematologic complications develop. The authors report a case of
      Fanconi anemia diagnosed in a child with no congenital abnormalities and normal
      bone marrow who first presented with a cerebellar medulloblastoma. The authors
      discuss diagnostic and therapeutic implications for such malignancies in Fanconi
      anemia.

PMID- 14707716
TI  - Spinal cord schwannomas mimicking drop metastases in a patient with
      intramedullary ependymoma and neurofibromatosis 2.
AB  - The authors describe a 9-year-old boy with a large spinal cord ependymoma whose
      apparent drop metastases on imaging studies were later demonstrated to be
      schwannomas. This finding led to the discovery of small bilateral acoustic
      neuromas and an intracranial meningioma, establishing the diagnosis of
      neurofibromatosis 2. The presence of additional radiographic abnormalities in a
      patient with a spinal cord tumor should prompt careful consideration of the
      diagnosis of neurofibromatosis 2, as early identification of this disorder may
      significantly affect patient management.

PMID- 14707717
TI  - Cure of hepatoblastoma with transcatheter arterial chemoembolization.
AB  - Until now surgical resection was still considered as the only choice of
      successful treatment of hepatoblastoma. Therefore, successful use of
      transcatheter arterial chemoembolization (TACE) alone to cure the unresectable
      hepatoblastoma in an infant was firstly reported. A 6-month-old boy presented
      with a huge abdominal mass and was found to have a hepatoblastoma of 17.5 cm x
      11.5 cm x 10 cm on computed tomography (CT) scan. The serum alpha-fetoprotein
      (AFP) was elevated to 6250 ng/mL. On the first TACE the main feeding arteries
      were completely occluded by stainless steel embolization coils. After one month
      tumor shrinkage was 75%, but a newly formed feeding artery was found and
      embolized on second TACE. Since the third TACE no newly formed feeding artery was
      found and 6 courses of intravenous chemotherapy were consolidated. On the last
      DSA and CT the tumor was completely disappeared and AFP returned to normal.
      During the follow-up he remained disease-free for 33 months until the present
      report. TACE may provide an additional promising choice in the treatment of
      hepatoblastoma.

PMID- 14707718
TI  - Pulmonary tuberculosis in a child receiving intensive chemotherapy for acute
      myeloblastic leukemia.
AB  - The authors describe a 6-year-old boy who developed pulmonary tuberculosis during
      intensive chemotherapy for acute myeloblastic leukemia (AML). The diagnosis of
      tuberculosis was made by PCR from an open lung biopsy, while a bacterial culture
      was negative. The patient was treated with triple tuberculostatic drug therapy,
      followed by two-drug therapy, while receiving maintenance chemotherapy for AML,
      including thioguanine and cytarabine. Pulmonary infiltrates resolved within 2
      months of treatment. However, possibly due to the bone marrow toxicity of the
      tuberculostatic drugs, the patient tolerated only low doses of cytostatic
      therapy. The boy is now 14 months off tuberculostatic treatment and 8 months off
      AML therapy. He is in remission of AML and tuberculosis.

PMID- 14707719
TI  - Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation
      from a family donor based on fetomaternal microchimerism in pediatric hematologic
      malignancies.
AB  - Based on recent fetomaternal microchimerism/tolerance theory, two children with
      acute lymphoblastic leukemia underwent non-T-cell-depleted hematopoietic stem
      cell transplants (SCT) from haploidentical HLA 2 loci-mismatched family donors
      (one from a sibling, one from the mother). Engraftment was achieved in two
      patients. In two recipients, acute graft-versus-host disease was limited to grade
      II or less, and no chronic graft-versus-host disease developed. Both of these
      patients have maintained complete remission for more than 8 months post-SCT. Non
      T-cell-depleted SCT from haploidentical HLA 2 loci-mismatched family donors seems
      feasible if microchimerism is detectable.

PMID- 14707720
TI  - Becker muscular dystrophy in a patient with Hodgkin's disease.
AB  - Genetic disease often predisposes to neoplastic processes because of either
      alterations in both oncogenes and tumor suppressor genes or imbalances in the
      cell cycle. The authors present the case of a 15-year-old boy with Hodgkin's
      disease associated with Becker muscular dystrophy. Becker muscular dystrophy is
      an X-linked neuromuscular disease due to in-frame mutations in the dystrophin
      gene, and it is considered a milder variant of Duchenne muscular dystrophy. In
      most patients with Becker muscular dystrophy, the myopathic process affects the
      myocardium, leading to cardiomyopathy.

PMID- 14707721
TI  - Reliability of splenic index to assess splenic involvement in pediatric Hodgkin's
      disease.
AB  - The purpose of this study was to determine the reliability of the splenic index
      (SI) in children with Hodgkin's disease (HD). Seventeen patients who underwent
      staging laparotomy for HD were included in this study. Pretreatment computed
      tomography scans of these patients were reviewed retrospectively to determine the
      SI. The specificity, sensitivity, positive and negative predictive values, and
      accuracy of the SI were calculated. The sensitivity and specificity of the SI
      were 50% and 66%, respectively. The SI alone accurately identified or ruled out
      involvement with HD in 10 of 17 patients. Positive and negative predictive values
      of the SI were 57% and 60%, respectively. Even with the use of the SI, computed
      tomography alone remains unreliable to determine splenic involvement in children
      with HD. Additional imaging studies, especially fluorodeoxyglucose positron
      emission tomography, may improve the clinical staging of HD.

PMID- 14707722
TI  - Secondary thyroid carcinoma after treatment of yolk sac tumor.

PMID- 14707723
TI  - Terminally modified oligodeoxynucleotides directed against p53 in an orthotopic
      xenograft model: a novel adjuvant treatment strategy for pancreatic ductal
      carcinoma.
AB  - OBJECTIVES: Investigation of a terminally modified oligodeoxynucleotide (ODN)
      directed against p53 mRNA (p53-3' polyethylene glycol-5' tocopherol ODN as a
      novel drug for pancreatic ductal carcinoma therapy in vitro and in vivo. METHODS:
      The impact of lipophilic modifications at the 5' end of p53-directed ODNs on
      cellular uptake was analyzed in vitro using proliferation assays, fluorescence
      activated cell sorting analysis, and confocal laser scanning microscopy. The in
      vivo effects of p53-PT-ODN on the growth of orthotopically xenografted human
      pancreatic ductal carcinoma cells (PancTuI) were studied in SCID beige mice.
      Distribution was examined in vitro and in vivo using Cy3-labeled ODNs. RESULTS:
      Terminally modified p53-PT-ODN showed excellent cellular uptake without using
      transfection reagents. Microscopically detectable levels of p53-PT-ODN were
      reached in vivo within 3 hours after intraperitoneal injection, even in
      extraperitoneal organs. At this time, Cy3-labeled p53-PT-ODN was found in solid
      tumor formations. We observed a significant inhibition of tumor growth (50%) in
      vivo at low doses of p53-PT-ODN, whereas at high doses, 2 of 9 animals had no
      detectable tumors at necropsy. When p53-PT-ODN was injected on the day of tumor
      cell inoculation, the growth inhibition of solid tumors was significantly
      stronger compared with that with delayed treatment. CONCLUSIONS: p53-Directed
      modified ODNs might be of therapeutic value in pancreatic ductal carcinoma,
      particularly as adjuvant therapy after pancreatic tumor resection.

PMID- 14707724
TI  - Detection of p53 gene mutations in the supernatant of pancreatic juice and plasma
      from patients with pancreatic carcinomas.
AB  - AIM: The sensitivity of pure pancreatic juice (PPJ) cytology for the diagnosis of
      pancreatic carcinoma (PCa) is still low. The usefulness of genetic analyses of
      PPJ seems to be limited because of insufficient sensitivity or false positivity.
      To improve the molecular diagnosis of PCa, we analyzed mutations of p53 together
      with K-ras in DNA extracted not only from the sediment but also from the
      supernatant of PPJ samples. METHOD: Polymerase chain reaction-single-strand
      conformation polymorphism and direct sequencing were used for analyses of p53
      mutations in exons 5-8. K-ras mutations at codon 12 were examined by mutant
      allele-specific amplification. RESULTS: In PPJ supernatant from patients with
      PCa, p53 and K-ras mutations were detected in 42.9% (9 of 21) and 81.0% (17 of
      21) of cases, respectively. The incidence of p53 and K-ras mutations in the
      sediment was 28.6% and 71.4%, respectively. By a combination assay with
      supernatant and sediment, p53 mutations were detected in 52.4% (11 of 21) of PCa
      cases. Moreover, p53 mutations were detected in 7 of 15 (46.7%) cases of PCa in
      which the cytologic diagnosis was negative. Among 25 patients with chronic
      pancreatitis (CP), none harbored mutant p53, although K-ras mutations were
      detected at an incidence of 28% (7 of 25) in the supernatant and 20% (5 of 25) in
      the sediment. In addition, mutant bands of p53 in plasma were detected in 2 of 11
      patients with PCa in whom p53 mutations were detectable in PPJ. CONCLUSION: These
      results suggest that the sensitivity of detection for p53 mutations with high
      cancer specificity could be improved by using the Sup in PPJ samples of PCa.
      Genetic analysis of p53 could complement PPJ cytology. p53 mutations were
      detectable in PCa from plasma samples.

PMID- 14707725
TI  - Expression of integrins in intraductal papillary-mucinous tumors of the pancreas
      as an indicator of malignancy.
AB  - INTRODUCTION AND AIMS: Intraductal papillary-mucinous tumors (IPMTs) of the
      pancreas are intraductal tumors with diffuse or segmental dilation of the
      pancreatic ducts and intraductal papillary growth with abundant mucous secretion.
      We examined clinicopathological features and immunohistochemical findings to
      investigate the malignancy of IPMTs. METHODOLOGY: Between April 1994 and December
      2002, 23 patients with IPMT underwent pancreatic resections at Nagoya City
      University Hospital, Japan. We immunohistochemically analyzed the expression of
      p53 protein, proliferating cell nuclear antigen, alpha6-integrin subunit,
      alpha5beta1 integrin, and interleukin-1 receptor type I in tumor specimens from
      the 23 patients with IPMT. RESULTS: The tumors were classified as intraductal
      papillary adenoma (n = 16), intraductal papillary adenocarcinoma and moderate
      dysplasia (n = 7). At a median follow-up of 42.9 months, 2 patients had died of
      this disease. The actuarial 5-year disease-free survival rate was 80.7%.
      Expression of the alpha6-integrin subunit was significantly strong in
      adenocarcinoma and moderate dysplasia tissues of IPMTs (P = 0.038). CONCLUSIONS:
      Our current results indicate that alpha6-containing integrin expression can be a
      significant marker of malignancy in IPMTs. We emphasize that immunohistochemical
      investigation of resected specimens is indispensable in cases of IPMT, so that
      appropriate postoperative treatments for malignant IPMTs are initiated to improve
      prognosis.

PMID- 14707726
TI  - Adenovirus-mediated transfer of a truncated fibroblast growth factor (FGF) type I
      receptor blocks FGF-2 signaling in multiple pancreatic cancer cell lines.
AB  - Pancreatic ductal adenocarcinomas (PDACs) overexpress several members of the
      fibroblast growth factor (FGF) family of ligands and the type I FGF receptor
      (FGFR-1), and enhanced FGF-2 protein levels correlate with shorter postoperative
      survival of patients with PDAC. In this study, we investigated the effects of FGF
      2 on cell proliferation and mitogen-activated protein kinase (MAPK) activation
      before and after abrogation of FGFR-1-dependent signaling in 4 pancreatic cancer
      cell lines (ASPC-1, COLO-357, MIA-PaCa-2, and PANC-1). Signaling was blocked by
      infecting the cells with an adenoviral vector encoding for a truncated FGFR-1
      (AdtrFGFR-1). FGF-2 enhanced the growth of all 4 cell lines and activated MAPK in
      3 of these cell lines. Infection with the AdtrFGFR-1 virus resulted in abundant
      expression of the truncated FGFR-1 at the RNA and protein level, markedly
      attenuated FGF-2-induced proliferation in all 4 tested cell lines, and decreased
      FGF-2-dependent MAPK activation in the 3 cell lines in which FGF-2 activated this
      pathway. These findings suggest that FGFR-1-mediated mitogenesis in multiple
      pancreatic cancer cells can be efficiently blocked with an adenoviral vector
      encoding a truncated FGFR-1, raising the possibility that AdtrFGFR-1 may
      ultimately have a therapeutic role in PDAC.

PMID- 14707727
TI  - Inhibitory effect of the lectin wheat germ agglutinin on the binding of 125I-CCK
      8s to the CCK-A and -B receptors of AR42J cells.
AB  - INTRODUCTION: Cholecystokinin (CCK) is a peptide hormone and plays a major role
      both in the regulation of pancreatic enzyme secretion and growth of the
      gastrointestinal tract. The pancreatic CCK receptors are highly glycosylated
      membrane proteins that are able to bind plant lectins such as wheat germ
      agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I). AIM AND METHODOLOGY: In
      preceding papers, we demonstrated an inhibition of CCK-8s induced Ca2+ signaling
      and secretion of rat pancreatic acini and AR42J cells by the lectins WGA and UEA
      I (Pancreas 2001;23:368-374). Here we studied the influence of WGA, UEA-I, and 22
      other lectins on 125I-CCK-8s binding on AR42J cells. A binding assay was used
      with 125I-CCK-8s and dexamethasone-stimulated AR42J cells, bearing CCK-A as well
      as CCK-B receptors. RESULTS: WGA inhibits 125I-CCK-8s binding in a dose-dependent
      manner. The binding is affected at concentrations of WGA >1 microg/mL. The EC50
      for inhibition is 8 microg/mL. At a concentration of 25 microg/mL, WGA inhibits
      the hormone binding 70%. This inhibition can be abolished by the specific sugars
      for WGA N,N',N"-triacetylchitotriose and N-acetylglucosamine, but not by N
      acetylneuraminic acid. UEA-I diminished hormone binding but without significance,
      although UEA-I binds to the fucose residues of receptor glycosylations. All other
      22 lectins tested here were ineffective. CONCLUSION: The blockage of CCK
      receptors by WGA explains the inhibition of CCK-8s induced Ca2+ signaling and the
      secretion of pancreatic acinar cells and AR42J cells. Although the inhibitory
      effect of WGA is in agreement with the findings of Santer et al, the results with
      UEA-I are in contrast to those of Santer et al (1990), who described a strong
      increase in 125I-CCK-8s binding to isolated crude rat pancreatic cell membranes
      in the presence of UEA-I.

PMID- 14707728
TI  - Tumor-stroma interaction of human pancreatic cancer: acquired resistance to
      anticancer drugs and proliferation regulation is dependent on extracellular
      matrix proteins.
AB  - INTRODUCTION: Pancreatic cancer is one of the major causes of cancer-related
      deaths in industrialized countries. It is known that pancreatic cancer is
      resistant to chemotherapy and that cancer cells are surrounded by extracellular
      matrix (ECM) proteins including collagen I, collagen IV, fibronectin, and
      laminin. AIMS: To examine the role of ECM proteins in acquired resistance to
      anticancer drugs and proliferation regulation in pancreatic cancers. METHODOLOGY
      AND RESULTS: We used an in vitro model of ECM-induced chemoresistance and cell
      proliferation of cancer cell lines (MIA PaCa-2, PANC-1, and Capan-1) with 3
      different malignancy grades and found that resistance to cytotoxic drugs and
      proliferation regulation was dependent on ECM proteins. Pancreatic cancer cell
      lines, especially MIA PaCa-2 cells, adhering to any of the ECM proteins showed
      decreased cytotoxicity of anticancer drugs, except for gemcitabine. PANC-1 and
      Capan-1 cells adhering to fibronectin, collagen I, and collagen IV proliferated
      more than the controls. CONCLUSION: ECM proteins have important roles in acquired
      resistance to anticancer drugs and cell proliferation regulation of pancreatic
      cancer cells. Therefore, the expression of ECM proteins in pancreatic cancer
      specimens could provide valuable information to aid anticancer drug cytotoxicity,
      and gemcitabine would be useful for treatment of patients with pancreatic cancer.

PMID- 14707729
TI  - Expression of multidrug resistance proteins in rat and human chronic
      pancreatitis.
AB  - BACKGROUND AND AIMS: The expression of the ABC-transporters MDR-1, MRP1, and MRP
      2 was investigated in healthy pancreas and in chronic pancreatitis tissue samples
      in rats and humans to evaluate their possible involvement in a multidrug
      resistance of the pancreas with consequences for the pharmacologic treatment of
      pancreatic diseases. METHODS: Human pancreatic tissue samples of healthy tissue
      and chronic pancreatitis were collected during pancreas surgery. In rats, the
      time-course of the expression of transporter proteins was studied 14, 28, and 56
      days after experimental induction of chronic pancreatitis. The expression of MDR
      1, MRP-1, MRP-2, and furthermore, LRP and PAP was investigated by RT-PCR, Real
      Time TaqManPCR, and immunohistochemistry. RESULTS: In rat pancreas, MDR-1 (P-gp)
      and MRP-1 but in human pancreas MDR-1 (P-gp), MRP-1 and MRP-2 were found to be
      expressed. Chronic pancreatitis lead to an increased transcription of mRNA of MDR
      1 (rat and human) and much lower, MRP-2 (human). CONCLUSIONS: The expression of P
      gp and related transporters could have impact on the metabolism, distribution,
      and availability of various compounds, including drugs, in the pancreas. The
      results indicate that this could be more pronounced in chronic pancreatitis.

PMID- 14707730
TI  - The effect of combination therapy of hyperbaric oxygen, meropenem, and selective
      nitric oxide synthase inhibitor in experimental acute pancreatitis.
AB  - Despite the new diagnostic and therapeutic advancements, acute pancreatitis has
      still high rate of morbidity and mortality. We aimed to evaluate the effects of
      hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT),
      and meropenem (MER) therapy in an experimental rat model of acute necrotizing
      pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis
      was induced in all groups except group 1. Treatment protocols were saline for
      group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for
      group 6, HBO + MER for group 7, and MER for group 8. All surviving animals were
      killed 48 hours after the induction of pancreatitis, and specimens were
      collected. Oxidative stress parameters, histopathologic scores and amylase levels
      were better in treatment groups than in the positive control group (group 2). The
      most favorable results were obtained in HBO treatment groups, especially in HBO +
      MER group (group 7). Our results indicate that adding HBO therapy to the
      antibiotic therapy will decrease oxidative stress parameters, serum amylase
      levels, and histopathological score. We suggest that adding the HBO therapy as an
      adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield
      improvement in the morbidity and mortality of the disease.

PMID- 14707731
TI  - Increased expression of hypoxia-inducible factor-1alpha, p48, and the Notch
      signaling cascade during acute pancreatitis in mice.
AB  - Acute pancreatitis (AP) is a complex disease that may be linked to acinar cell
      apoptosis and inadequate acinar cell replacement. Differentiation of acinar cells
      is regulated by p48, a DNA binding subunit of the transcription factor PTF1, and
      the Notch signaling pathway. Acinar cell apoptosis is triggered by oxygen
      deprivation, ie, hypoxia, by activation of hypoxia inducible factor-1alpha (HIF
      1alpha). The aim of this study was to characterize by Northern blot analyses
      expression of HIF-1alpha, HIF-1alpha-inducible genes (GLUT-1, VEGF, p53), p48,
      and genes involved in the Notch signaling pathway (Notch-1, Dll1, RBP-Jk, HES-1)
      during cerulein-induced AP in mice. Maximal expression of HIF-1alpha, HIF-1alpha
      inducible genes, p48, and Notch signaling genes occurred 8-12 hours after
      induction of AP. Maximal expression of p53 occurred 12-48 hours after induction
      of AP. These findings demonstrate that multiple pancreatic genes are activated
      acutely during AP that support pancreatic cell replenishment, regulation of
      expression of acinar cell-specific genes, and apoptosis.

PMID- 14707733
TI  - Pylorus preservation has no impact on delayed gastric emptying after pancreatic
      head resection.
AB  - OBJECTIVES: Delayed gastric emptying (DGE) has been specifically attributed to
      pylorus-preserving pancreaticoduodenectomy (PPPD). As PPPD has been shown to be
      comparable with the classic Kausch-Whipple pancreaticoduodenectomy (KWPD) in
      terms of oncological radicality, DGE has advanced to be the leading argument for
      hemigastrectomy in PD. METHODS: A prospective, nonrandomized comparison of
      patients undergoing PPPD (n = 113), KWPD (n = 19), and duodenum-preserving,
      pancreatic head resection (DPPHR, n = 18) for various diseases was performed.
      First, groups were analyzed with regard to structural similarity; then, they were
      compared with special emphasis on DGE and other postoperative complications.
      Finally, further prognostic factors were sought that had an impact on DGE.
      RESULTS: The PPPD group was comparable with the KWPD group, but not to the DPPHR
      population. The in-clinic course after DPPHR compared favorably with PPPD as well
      as KWPD, and, here, no DGE occurred. The overall morbidity rates of PPPD and KWPD
      were comparable; 1 patient died in hospital (mortality rate, 0.7%). The gastric
      tube after PPPD and KWPD could be withdrawn at a median of 2 and 3 days,
      respectively, a liquid diet was started after 4 and 5 days, respectively, and a
      full diet was tolerated after 10 days each (n.s.). DGE was distributed evenly
      among PPPD (12%) and KWPD patients (21%, n.s.), and it was noted almost
      exclusively when other postoperative complications were present (P < 0.0001). No
      further prognostic factors influencing DGE could be identified. CONCLUSION:
      Pylorus preservation does not increase the frequency of DGE. DGE almost
      exclusively occurs as a consequence of other postoperative complications.
      Therefore, DGE should not be used as an argument to advocate hemigastrectomy in
      PPPD.

PMID- 14707732
TI  - Pancreatic function after severe acute biliary pancreatitis: the role of
      necrosectomy.
AB  - OBJECTIVES: To investigate the recovery of pancreatic function after severe acute
      biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine
      and exocrine functions. METHODS: Prospective cohort study including 39 patients
      with severe ABP. According to need or no need for surgical necrosectomy, patients
      were further subdivided into 2 groups. Functional pancreatic evaluation was
      carried out 12 months after the ABP episode. Endocrine function was evaluated by
      an oral glucose tolerance test and exocrine function by fecal fat excretion,
      fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS: Most of the
      patients with necrosectomy had an abnormal exocrine pancreatic function, with
      steatorrhea in 25%. In the group without surgery, exocrine function was
      pathologic in only 13.3% and there were no cases of steatorrhea. Endocrine
      function was pathologic in 75% of patients undergoing necrosectomy versus 26.7%
      in the nonoperated group. In this latter group, the patients with abnormal
      endocrine function did not require insulin therapy, while in 33.3% of patient in
      the necrosectomy group insulin was necessary. CONCLUSIONS: In our homogeneous
      series of severe ABP, necrosectomy impaired significantly pancreatic endocrine
      and exocrine function. On the other hand, most patients with the same origin and
      severity index, but without surgical debridement, maintained normal pancreatic
      function.

PMID- 14707734
TI  - Pancreas graft thrombosis: is there a role for trypsin.
AB  - PURPOSE: Thrombosis of the pancreas graft is the main cause of early graft loss
      in pancreas transplantation. We investigated whether hypercoagulability develops
      locally in the pancreas and contributes to thrombosis formation because of
      ischemia or reperfusion injury. It was further hypothesized that this might be
      induced by excessive intravascular trypsin activity. METHODS: Ten Patients
      undergoing pancreas transplantation were studied. In addition to the standard
      operation a 14 French catheter was inserted in the distal part of the splenic
      vein of the pancreas graft. After reperfusion blood samples were drawn
      simultaneously from the splenic vein of the pancreas graft (local samples) and
      the radial artery (systemic samples) at 0,1,2,5,10,30, and 60 minutes after
      reperfusion. RESULTS: After reperfusion a progressive hypercoagulability
      developed locally in the pancreas as seen by an increase of thrombin-antithrombin
      complexes and only a transient increase of plasmin-antiplasmin complexes. In
      addition antithrombin 3 and protein c decreased systemically. The alterations
      seem not to be triggered by trypsin because trypsin activity locally remained low
      despite trypsinogen release and activation as assessed by trypsinogen activation
      peptides. CONCLUSION: Local hypercoagulability might contribute to the
      development of graft thrombosis, however, the mechanism seems not to be related
      to ectopic trypsin activation.

PMID- 14707735
TI  - The enzyme levels in blood are not affected by oral administration of a
      pancreatic enzyme preparation (Creon 10,000) in pancreas-insufficient pigs.
AB  - After oral intake, small amounts of intact protein may be absorbed into the blood
      circulation. The current study investigated whether orally administered
      pancreatic enzymes were absorbed from the intestine. The study included 28 pigs;
      3 control pigs with intact pancreatic function and 25 pigs that were made
      exocrine pancreas insufficient by duct ligation (20 pigs) or total pancreatectomy
      (5 pigs). The pigs received a pancreatic enzyme preparation (0, 2, 4, or 8 g of
      Creon 10,000) together with the feed. The blood plasma was analyzed for
      pancreatic lipase activity with a [3H]-triolein substrate assay, while
      (pro)colipase and cationic trypsin(ogen) levels were measured with enzyme-linked
      immunosorbent assay (ELISA). Administration of Creon (0-8 g) caused no
      significant changes in plasma (pro)colipase or cationic trypsin(ogen) levels.
      Lipase activity peaks in plasma samples were found, but they did not correspond
      to the administration of Creon. The potential source of these plasma lipase
      activity peaks is discussed. The results showed no absorption into blood of
      pancreatic enzymes after oral administration (0, 2, 4, or 8 g of Creon mixed with
      100 g of feed) to pancreas-insufficient pigs.

PMID- 14707736
TI  - Is a 15-minute collection of duodenal secretions after secretin stimulation
      sufficient to diagnose chronic pancreatitis?
AB  - BACKGROUND: Standard hormonal stimulation tests of pancreatic function use a 60-
      to 90-minute collection of pancreatic secretions. A shorter 15-minute collection
      time has been proposed to increase the feasibility of the secretin stimulation
      test. The accuracy of this brief collection period for the diagnosis of chronic
      pancreatitis has not been well defined. METHODS: We retrospectively evaluated the
      accuracy of a 15-minute collection period by comparing the results of 633
      complete standard secretin tests (60 minutes) to the result using only the first
      15-minute collection of the same test. The gold standard used for the diagnosis
      of chronic pancreatitis was the final result of the complete 60-minute secretin
      stimulation test. RESULTS: The specificity of the first 15-minute collection was
      34.6% (95% CI, 30.03%-39.21%). The positive predictive value was 44.9% (95% CI,
      40.5%-49.3%). The accuracy was 57.3% (95% CI, 53.01% 59.34%). CONCLUSIONS: Using
      only the first 15-minute collection period in a standard 60-minute secretin test
      is inaccurate in the diagnosis of chronic pancreatitis.

PMID- 14707737
TI  - Diagnosis and treatment of VIPoma in China: (case report and 31 cases review)
      diagnosis and treatment of VIPoma.
AB  - OBJECTIVES: To discuss the experience of diagnosis and treatment of VIPoma by
      summarizing clinical information of 31 patients with VIPoma in China. METHODS: To
      analyze clinical manifestations, laboratory examinations, imaging features,
      operation, pathologic findings, and follow-up survey of 31 patients, among them 1
      case was from our hospital and the other 30 cases were reported in Chinese
      literature from 1977 to 2002. RESULTS: Periodical backache, skin rash, and polyps
      of colon were never reported previously, all of which except polyps disappeared
      after operation. Partial resection of superior mesenteric vein was also never
      reported. The mean serum value of VIP which had been very high before operation,
      decreased markedly after the operation (963.2 pg/ml Versus 131.9 pg/ml),the
      immunohistochemical expression of many kinds of digestive hormone including VIP
      presented positive. Hepatic involvement was 29.0%,nodal metastasis was 9.7%.
      CONCLUSIONS: VIPoma is rare. Typical symptoms and the serum value of VIP are keys
      to diagnosis before operation, Surgical resection is the most effective means for
      cure. surgical debulking of the tumor, somatostatin analogues can be used for
      good palliation.

PMID- 14707738
TI  - Epstein-Barr virus-associated lymphoepithelial carcinoma in the pancreas.
AB  - Lymphoepithelial carcinoma is a relatively common malignancy in the
      nasopharyngeal region, but it rarely occurs at other sites. We report a
      lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated
      on for a gastric stump carcinoma 7 years previously. The solitary tumor in the
      pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The
      tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled
      all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node
      metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early
      RNA (EBER) was detected in the majority of tumor cells using in situ
      hybridization. Nuclear EBER signals were also detected in the previously operated
      gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration
      but otherwise displayed a histology different from lymphoepithelial carcinoma and
      did not show local recurrence. Even though an unusually late metastasis of the
      gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient
      developed an EBV-related pancreatic lymphoepithelial carcinoma as a second
      primary tumor, based on the considerable delay of this tumor manifestation, the
      unusual site, the pathologic presentation, the exclusively peripancreatic nodal
      spread, and the different histology of the lesion.

PMID- 14707739
TI  - Complete pathologic responses to preoperative chemoradiation in two patients with
      adenocarcinoma of the pancreas.

PMID- 14707741
TI  - An epitome to savor; a work of art and love.

PMID- 14707740
TI  - Autoimmune pancreatitis in the spectrum of autoimmune exocrinopathy associated
      with sialoadenitis and anosmia.

PMID- 14707742
TI  - Infliximab: a new therapeutic agent in acute pancreatitis?
AB  - PURPOSE: Tumor necrosis factor alpha (TNF-alpha) has a central role in the
      pathogenesis of acute pancreatitis and related systemic complications. The aim of
      this study is to investigate the therapeutic effectiveness of monoclonal TNF
      antibody (infliximab) in acute edematous and severe necrotizing pancreatitis
      models in rats. METHODS: One hundred rats were randomly divided into 10 groups.
      Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20
      microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing
      pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into
      the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous
      infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase
      enzyme activity (MPO), and pulmonary changes were assessed. RESULTS: Infliximab
      treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L
      versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus
      1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and
      MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to
      decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum
      amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated
      both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also
      alleviated alveolar edema and acute respiratory distress syndrome like pulmonary
      complications, but the difference was not significant. CONCLUSIONS: Chimeric TNF
      antibody, infliximab, should be evaluated for treatment of acute pancreatitis.

PMID- 14707743
TI  - Nitric oxide protects against pancreatic subcellular damage in acute
      pancreatitis.
AB  - OBJECTIVES: Oxidative stress involvement in damage to the pancreas in acute
      pancreatitis (AP) is well documented. However, little is known about oxidative
      damage occurring in the different subcellular fractions of pancreatic cells. The
      aim of this study was to ascertain the main targets of oxidative damage inside
      cells after AP and the role of endogenous nitric oxide (NO) in it. METHODS: A
      model of cerulein-induced AP in rats was used and N-nitro-l-arginine methyl ester
      (l-NAME) was administered as an NO production inhibitor. After pancreatitis
      induction, indicative parameters of lipid peroxidation and protein oxidation
      together with some enzymatic and nonenzymatic endogenous free radical scavengers
      were assessed in serum and pancreatic subcellular fractions. CONCLUSIONS: In
      pancreatitic rats, malondialdehyde and protein carbonyl group concentrations were
      significantly increased (P < 0.05) in serum and some fractions. The increases
      were higher in l-NAME-treated rats (P < 0.05). Superoxide dismutase and catalase
      activities were also increased (P < 0.05) but were decreased (P < 0.05) with l
      NAME. The alpha-tocopherol concentration diminished (P < 0.05) in serum and all
      the studied subcellular fractions and the decrease was stronger in l-NAME-treated
      rats. Our data suggest that microsomes followed by lysosomal + mitochondrial are
      the fractions most susceptible to oxidative damage in AP. Endogenous NO plays a
      protective role against oxidative damage to subcellular fractions.

PMID- 14707744
TI  - A dithiocarbamate analogue decreases intraislet cell infiltration and the
      incidence of diabetes mellitus in the genetic diabetes-prone BB rat.
AB  - SUMMARY: Dithiocarbamates are a class of agents that have interesting biologic
      properties including the ability to limit the production and/or action of nitric
      oxide (NO). These agents are also potential immunosuppressant agents. Since
      immunosuppressant agents have been examined for remission of disease in clinical
      trials, we wanted to examine whether a dithiocarbamate analogue, NOX-200, might
      inhibit diabetogenesis in the genetic diabetes-prone BB rat model.
      Immunohistochemical analysis revealed inducible NO synthase (iNOS) gene
      expression in pancreatic islets of both normoglycemic and hyperglycemic diabetes
      prone BB rats but not in diabetes-prone BB rats at the early age of 30 days or in
      diabetes-resistant BB rats. A qualitative decrease in immunostaining for iNOS was
      also observed in the pancreata of drug-treated animals. Long-term treatment with
      NOX-200, used alone or in combination with low-dose cyclosporine (CsA),
      significantly reduced the incidence of diabetes mellitus. In the subset of
      animals that became diabetic, NOX-200 did not alter either the time to onset of
      hyperglycemia or the level of hyperglycemia, insulinopenia, or lymphocytic cell
      infiltration into the pancreas. In contrast, in animals that did not develop
      hyperglycemia, treatment with NOX-200 decreased inflammatory cell infiltration
      into the pancreas equipotent to that seen using CsA. These studies demonstrate
      the potential therapeutic efficacy of dithiocarbamates to oppose the development
      of autoimmune insulin-dependent diabetes mellitus by limiting inflammatory cell
      activation/infiltration.

PMID- 14707746
TI  - Memorable medical mentors: influences.

PMID- 14707745
TI  - CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating
      lymphocytes and dendritic cells improve the prognosis of patients with pancreatic
      adenocarcinoma.
AB  - OBJECTIVE: Recent studies have demonstrated the importance of tumor immunity for
      a cancer patient's prognosis. In some types of cancer, it has been shown through
      immunohistochemical analysis that the existence of CD8+ tumor-infiltrating
      lymphocytes (TILs) is a crucial factor in determining prognosis. In an
      experimental model, CD4+ lymphocytes together with CD8+ lymphocytes contributed
      significantly to tumor immunity. METHODS: Specimens were taken from 80 surgically
      resected pancreatic adenocarcinomas between 1992 and 1999. Immunohistochemical
      staining of CD4, CD8, and S100 protein was performed, and the levels of these
      proteins were determined by microscopic analysis. The percentages of patients in
      the CD4(+) and CD8(+) groups were 59% (47/80) and 25% (16/80), respectively. When
      separated into 4 groups, CD4/8(+/+), CD4/8(+/-), CD4/8(-/+) and CD4/8(-/-), the
      overall survival rate was significantly higher in CD4/8(+/+) patients (13 cases)
      compared with those in all other groups combined (67 cases; P = 0.0098).
      CD4/8(+/+) status was negatively correlated with tumor depth and TNM stage.
      Multivariate analyses showed that CD4/8(+/+) status was an independent favorable
      prognostic factor. The number of tumor-infiltrating S100 protein positive cells
      was also significantly higher in the CD4/8(+/+) group than in others (P =
      0.0084). CONCLUSIONS: In pancreatic adenocarcinoma, the presence of CD4+ TILs
      together with CD8+ TILs serves as a good indicator of the patient's outcome after
      surgical treatment.

PMID- 14707747
TI  - Truth-telling and the law: the bottom line of the Institute of Medicine's report
      on error.

PMID- 14707748
TI  - Neurologic complication of labor analgesia: facts and fiction.
AB  - Regional anesthesia has become a hallmark of modern obstetric anesthesia practice
      and a paramount technique for labor analgesia. Neurologic complications
      associated with present-day labor analgesia are thought to be unusual; however,
      they can occasionally complicate peripartum obstetric and anesthetic management
      of pregnant patients. To date, no review article in obstetric literature has
      specifically addressed the issue of possible neurologic anesthetic complications
      attributed to labor analgesia. Therefore, a series of systemic literature
      searches (Medline) to identify the articles on neurologic complication of labor
      analgesia was conducted. This review article summarizes the evidence from
      published articles on this topic, with particular emphasis on the mechanism of
      neurologic injury, lidocaine-related transient neurologic symptoms,
      anticoagulation and vascular compromise, diagnostic evaluation, and prevention of
      neurologic obstetric anesthesia-related neurologic injury in pregnancy.

PMID- 14707749
TI  - Nonobstetric surgery during pregnancy: what are the risks of anesthesia?
AB  - The need for anesthesia and surgery during pregnancy occurs in 1.5% to 2.0% of
      all pregnancies. Each year, over 75,000 pregnant women in the United States
      undergo nonobstetric surgery. The operations include those directly related to
      pregnancy (e.g., cerclage), those indirectly related to pregnancy (e.g., ovarian
      cystectomy), and those unrelated to gestation (e.g., appendectomy,
      cholecystectomy). The diagnosis of any medical condition requiring surgical
      intervention in pregnancy often raises questions about the safety of both surgery
      and anesthesia in these patients. This controversy was primarily attributed to
      the lay press speculations that surgery and anesthesia in pregnancy could pose
      hazards to the mother and fetus. Despite these concerns, the safety of
      nonobstetric surgery and anesthesia in pregnancy has been well established, and
      many pregnant women are safely anesthetized everyday without ill effects for the
      mother or fetus.

PMID- 14707750
TI  - International conference on objective measurement: applications of Rasch analysis
      in health care.

PMID- 14707751
TI  - Controversy and the Rasch model: a characteristic of incompatible paradigms?
AB  - The development of Rasch models in educational and psychologic measurement in the
      1960s coincided with the introduction of other similar models, now described as
      models of item response theory (IRT). The application of IRT models has now
      extended to other social sciences, including health. Originally, there was
      substantial controversy between those who saw Rasch models as simply special
      cases of IRT models and those who saw them as essentially different. Because
      these different perspectives continue to manifest themselves in various ways, it
      seems relevant to understand the source of the original controversy. This paper
      attempts to do so by invoking Kuhn's studies in the history and philosophy of
      science at 3 levels. First, it suggests that the 2 perspectives reflect Kuhn's
      concept of legitimate, incompatible paradigms in which controversy is a typical
      manifestation. Second, because Kuhn recognizes individual histories in the
      development of paradigms, Rasch's own shift in perspective is summarized. Third,
      because proponents of the Rasch models emphasize the models' compatibility with
      fundamental measurement found in physical science, an analogy is made between how
      Kuhn explains the role of measurement in the physical sciences and how proponents
      of Rasch models explain the role of these models in the social sciences. In
      particular, these roles cannot be gleaned from textbooks in science and
      statistics, respectively.

PMID- 14707752
TI  - A comparison of the separation ratio and coefficient alpha in the creation of
      minimum item sets.
AB  - BACKGROUND: Short-form outcomes measures are becoming common in response to
      demands for increased efficiency in health care. This study examines Rasch
      measurement as an aid to selecting items for short form tests. The focus of this
      paper is on maintaining test quality while reducing items. The separation ratio
      (SR) aids item reduction by indicating how removing items impacts measurement
      precision. Results of the SR and coefficient alpha are compared. OBJECTIVES: To
      demonstrate the use of Rasch measurement to shorten clinical outcomes measures
      and to compare the separation ratio and coefficient alpha in evaluating when item
      reduction improved efficiency without sacrificing measurement precision. RESEARCH
      DESIGN: Retrospective analysis of existing health outcomes data. SUBJECTS: A
      convenience sample of 58 patients receiving cataract surgery. MEASURES: The 14
      items of the VF-14 (a measure of visual functioning), the published subset of
      items from this test (the VF-7), and 5 other 7-item combinations of the items.
      RESULTS: The largest coefficient alpha was obtained from the VF14 (.84) while the
      largest separation ratio (2.67) was obtained from the 7-item subtest with the
      reduced rating scale. CONCLUSIONS: This study demonstrated one way that Rasch
      measurement can be helpful in selecting items for minimum item sets while
      maintaining test precision. Both alpha and the separation ratio provide
      information about how a sample performed with a given test although variations in
      measurement precision may not always be detected with alpha.

PMID- 14707753
TI  - Comparing alternative Rasch-based methods vs raw scores in measuring change in
      health.
AB  - OBJECTIVES: To compare alternative Rasch-based approaches to the assessment of
      change over time through the example of an outcome measure used in total hip
      replacement surgery. SUBJECTS: Preoperative data were collected on 1424 patients
      receiving total hip replacement surgery; 1221 (86%) were sent follow-up
      questionnaires 1 year after surgery. MEASURES: The 12-item Oxford Hip Score (OHS)
      questionnaire administered preoperatively and 1-year postoperatively. METHODS:
      Subscales of the OHS for pain and functional impairment were examined for
      unidimensionality and item invariance. Two criteria were used to examine Rasch
      based measurement of the 2 subscales. Advantages of Rasch measurement were
      examined in terms of whether it produced improved discrimination of outcomes of
      patients (1) undergoing different levels of complexity of surgery; and (2)
      reporting different retrospective judgments of the success of their surgery.
      Using the method of relative precision in relation to groups of patients
      distinguished in these 2 ways, change scores using Likert scoring methods were
      compared with 2 Rasch scoring methods: (1) separate analyses of the 2 time
      points; and (2) a common scale analysis obtained by stacking patients from the 2
      time points. RESULTS: Less evidence for item invariance over time was found for
      the pain subscale. Other evidence supported treating subscales as unidimensional.
      Whichever Rasch scoring method was used, some gains in precision over standard
      Likert scoring were obtained in discriminating between groups of patients.
      CONCLUSIONS: The evidence from the current study suggests that there may be some
      gains in sensitivity to change of outcome measures from different Rasch-based
      scoring approaches.

PMID- 14707754
TI  - Assessing and adjusting for cross-cultural validity of impairment and activity
      limitation scales through differential item functioning within the framework of
      the Rasch model: the PRO-ESOR project.
AB  - INTRODUCTION: In Europe it is common for outcome measures to be translated for
      use in other languages. This adaptation may be complicated by culturally specific
      approaches to certain tasks; for example, bathing. In this context the issue of
      cross-cultural validity becomes paramount. OBJECTIVE: To facilitate the pooling
      of data in international studies, a project set out to evaluate the cross
      cultural validity of impairment and activity limitation measures used in
      rehabilitation from the perspective of the Rasch measurement model. METHODS:
      Cross-cultural validity is assessed through an analysis of Differential Item
      Functioning (DIF) within the context of additive conjoint measurement expressed
      through the Rasch model. Data from patients undergoing rehabilitation for stroke
      was provided from 62 centers across Europe. Two commonly used outcome measures,
      the Mini-Mental State Examination (MMSE) and the Functional Independence Measure
      (FIM) motor scale are used to illustrate the approach. RESULTS: Pooled data from
      3 countries for the MMSE were shown to fit the Rasch model with only 1 item
      displaying DIF by country. In contrast, many items from the FIM expressed DIF and
      misfit to the model. Consequently they were allowed to be unique across
      countries, so resolving the lack of fit to the model. CONCLUSIONS: Where data are
      to be pooled for international studies, analysis of DIF by culture is essential.
      Where DIF is observed, adjustments can be made to allow for cultural differences
      in outcome measurement.

PMID- 14707755
TI  - Activity outcome measurement for postacute care.
AB  - BACKGROUND: Efforts to evaluate the effectiveness of a broad range of postacute
      care services have been hindered by the lack of conceptually sound and
      comprehensive measures of outcomes. It is critical to determine a common
      underlying structure before employing current methods of item equating across
      outcome instruments for future item banking and computer-adaptive testing
      applications. OBJECTIVE: To investigate the factor structure, reliability, and
      scale properties of items underlying the Activity domains of the International
      Classification of Functioning, Disability and Health (ICF) for use in postacute
      care outcome measurement. METHODS: We developed a 41-item Activity Measure for
      Postacute Care (AM-PAC) that assessed an individual's execution of discrete daily
      tasks in his or her own environment across major content domains as defined by
      the ICF. We evaluated the reliability and discriminant validity of the prototype
      AM-PAC in 477 individuals in active rehabilitation programs across 4
      rehabilitation settings using factor analyses, tests of item scaling, internal
      consistency reliability analyses, Rasch item response theory modeling, residual
      component analysis, and modified parallel analysis. RESULTS: Results from an
      initial exploratory factor analysis produced 3 distinct, interpretable factors
      that accounted for 72% of the variance: Applied Cognition (44%), Personal Care &
      Instrumental Activities (19%), and Physical & Movement Activities (9%); these 3
      activity factors were verified by a confirmatory factor analysis. Scaling
      assumptions were met for each factor in the total sample and across diagnostic
      groups. Internal consistency reliability was high for the total sample (Cronbach
      alpha = 0.92 to 0.94), and for specific diagnostic groups (Cronbach alpha = 0.90
      to 0.95). Rasch scaling, residual factor, differential item functioning, and
      modified parallel analyses supported the unidimensionality and goodness of fit of
      each unique activity domain. CONCLUSIONS: This 3-factor model of the AM-PAC can
      form the conceptual basis for common-item equating and computer-adaptive
      applications, leading to a comprehensive system of outcome instruments for
      postacute care settings.

PMID- 14707756
TI  - Refining the conceptual basis for rehabilitation outcome measurement: personal
      care and instrumental activities domain.
AB  - BACKGROUND: Rehabilitation outcome measures routinely include content on
      performance of daily activities; however, the conceptual basis for item selection
      is rarely specified. These instruments differ significantly in format, number,
      and specificity of daily activity items and in the measurement dimensions and
      type of scale used to specify levels of performance. We propose that a
      requirement for upper limb and hand skills underlies many activities of daily
      living (ADL) and instrumental activities of daily living (IADL) items in current
      instruments, and that items selected based on this definition can be placed along
      a single functional continuum. OBJECTIVE: To examine the dimensional structure
      and content coverage of a Personal Care and Instrumental Activities item set and
      to examine the comparability of items from existing instruments and a set of new
      items as measures of this domain. METHODS: Participants (N = 477) from 3
      different disability groups and 4 settings representing the continuum of
      postacute rehabilitation care were administered the newly developed Activity
      Measure for Post-Acute Care (AM-PAC), the SF-8, and an additional setting
      specific measure: FIM (in-patient rehabilitation); MDS (skilled nursing
      facility); MDS-PAC (postacute settings); OASIS (home care); or PF-10 (outpatient
      clinic). Rasch (partial-credit model) analyses were conducted on a set of 62
      items covering the Personal Care and Instrumental domain to examine item fit,
      item functioning, and category difficulty estimates and unidimensionality.
      RESULTS: After removing 6 misfitting items, the remaining 56 items fit acceptably
      along the hypothesized continuum. Analyses yielded different difficulty estimates
      for the maximum score (eg, "Independent performance") for items with comparable
      content from different instruments. Items showed little differential item
      functioning across age, diagnosis, or severity groups, and 92% of the
      participants fit the model. CONCLUSIONS: ADL and IADL items from existing
      rehabilitation outcomes instruments that depend on skilled upper limb and hand
      use can be located along a single continuum, along with the new personal care and
      instrumental items of the AM-PAC addressing gaps in content. Results support the
      validity of the proposed definition of the Personal Care and Instrumental
      Activities dimension of function as a guide for future development of
      rehabilitation outcome instruments, such as linked, setting-specific short forms
      and computerized adaptive testing approaches.

PMID- 14707757
TI  - Postscript: Applications of Rasch analysis in health care.

PMID- 14707760
TI  - Regular exercise as an effective approach in antihypertensive therapy.
AB  - PURPOSE: Exercise has been well documented to exert a beneficial effect on
      cardiovascular health. The effective control of arterial pressure (BP) is
      essential from the standpoint of cardiovascular prevention. So far, no study has
      determined the long-term effect of regular training as a monotherapy on both BP
      at rest and during exercise. METHODS: Therefore, 10 subjects with hypertension
      (aged 43 +/- 3 yr) were studied in order to define BP response to long-term
      aerobic training. BP measurements were obtained at rest and during ergometry (50
      100 W). Patients were instructed to exercise weekly (2 x 60 min aerobic
      exercise). RESULTS: BP during exercise (100 W) did fall already after 6 months of
      regular training from 184 +/- 10/107 +/- 6 to 170 +/- 10/100 +/- 7, and this was
      associated with a 14% decrease in the rate-pressure product (at 100 W). After 18
      months of training, there were further reductions in BP, at rest from 139 +/-
      9/96 +/- 6 to 133 +/- 14/91 +/- 7 (P < 0.05) and during ergometry (100 W) from
      184 +/- 10/107 +/- 6 to 172 +/- 8/96 +/- 6 mm Hg (P < 0.001). During a 3-yr
      follow-up, BP continued to decrease significantly to 130 +/- 13/87 +/- 7 mm Hg at
      rest and 167 +/- 9/92 +/- 6 mm Hg during exercise. No significant changes in body
      weight were documented during the training period. CONCLUSION: The data
      demonstrate that long-term aerobic exercise is associated with a decrease in BP
      at rest and during exercise, which is comparable to that of drug therapies. This
      antihypertensive effect of regular training can be maintained as long as 3 yr.

PMID- 14707761
TI  - Physical activities and low back pain: a community-based study.
AB  - PURPOSE: Very little is known about the relationship between physical activity
      and low back pain (LBP) in general populations. This study aimed to evaluate the
      relationship between different dimensions of physical activity and LBP among all
      adults of a defined community. METHODS: A cross-sectional survey addressed all
      adults aged 22-70 of a single town. Inhabitants were asked to complete a self
      administered questionnaire regarding physical activities, LBP, and related
      characteristics. The Beacke Physical Activity Questionnaire evaluated physical
      activity, and the Modified Roland and Morris Disability Questionnaire, a pain
      severity scale, and the Pain Symptoms Frequency and Bothersomeness Indices
      evaluated LBP. RESULTS: High occupational activity demands contributed to
      increased LBP prevalence, and, conversely, high sporting activity participation
      contributed to a decline in all LBP measures. Subjects free of LBP and subjects
      who participate in sporting activities are more likely not to smoke and not to
      participate in high occupational activity demands. Type of sporting activity was
      not associated with LBP prevalence or severity. CONCLUSIONS: Different dimensions
      of physical activity yield different relationships to LBP. There are several
      shared characteristics of those participating in sport on a regular basis and
      those free of LBP. Both groups present a healthier lifestyle. Although LBP was
      less frequent among those who participate in sporting activities, participating
      in sporting activities did not contribute independently to a lower prevalence of
      LBP. However, once LBP was established, participating in sporting activities
      contributed indirectly to its severity.

PMID- 14707762
TI  - Protecting muscle ATP: positive roles for peripheral defense mechanisms
      introduction.
AB  - Skeletal muscle has evolved an impressive array of mechanisms for peripherally
      mediated control of ATP homeostasis. Some of these mechanisms are intracellular,
      and others are extracellular and include influences on the cross-bridge cycle
      itself and substrate supply. This paper introduces three distinctly different
      topics that nevertheless all have ATP defense in common. The role of ADP in
      fatigue is controversial but has recently been more clearly delineated so that an
      effect on alleviating force declines during extreme fatigue is plausible. AMP
      plays its role by activating the protein-kinase, AMPK, which is a key sensor of
      cellular energy stress. AMPK has different isoforms, is not uniformly distributed
      in the cell, and its activation is carefully controlled. It has multiple effects
      including improvements in substrate supply for the metabolic pathways producing
      ATP and inhibition of anabolic processes to further spare ATP. Red blood cells
      have the capacity to sense hypoxia and to release vasodilators where there is a
      locally increased demand for blood supply. The papers in this series emphasize
      the important positive roles of metabolites and sensors of fatigue in the balance
      between ATP supply and demand.

PMID- 14707763
TI  - Can any metabolites partially alleviate fatigue manifestations at the cross
      bridge?
AB  - During exercise, intracellular homeostasis depends on the matching of adenosine
      triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in
      communicating the extent of ATP demand to the metabolic supply pathways. During
      fatigue from high-intensity exercise, a major change in the intracellular milieu
      of skeletal muscle is not ATP depletion but metabolite accumulation that affects
      the actomyosin cross-bridge interaction. The resulting reduction in myosin ATPase
      activity, cross-bridge turnover rate, and velocity of contraction can be
      considered a useful downregulation of ATP demand. Although maximal force is
      reduced, it is reduced less than myosin ATPase activity. In combination,
      efficiency of force production at the cross-bridge is thus enhanced. This is a
      second useful role for metabolites during fatigue because the total ATP cost per
      unit of force is partially reduced. Theoretical models predict that ADP may
      alleviate some effects of fatigue by further enhancing cross-bridge efficiency,
      thus providing a third useful role for metabolite accumulation. Recent
      experimental evidence reviewed here suggests that this occurs when ATP
      concentration is dramatically reduced. Single-fiber chemical analyses of fatigued
      muscle show lower ATP concentrations than other methods, but whether the
      appropriate microenvironments for effective competition by ADP for the nucleotide
      binding site occur around some or all of the cross-bridges remains technically
      difficult to prove at this time. During fatigue, muscle activation is also
      decreased, a response that potentially has the greatest effect on ATP demand
      supply matching. I propose that the mismatch between the expected force
      production relative to muscle activation and the reduced force production from
      inorganic phosphate accumulation is the peripheral signal for reduced activation
      and is therefore the fourth useful role of metabolites in alleviating fatigue.

PMID- 14707764
TI  - AMP-activated protein kinase: a key system mediating metabolic responses to
      exercise.
AB  - The finding that AMP-activated protein kinase (AMPK) was activated by exercise in
      skeletal muscle, reported by Winder and Hardie in 1996, provided the first hint
      that this signaling pathway might represent the elusive and long-sought system
      that was responsible for the metabolic changes associated with exercise. It
      triggered an increasing volume of research that has now largely vindicated this
      hypothesis although, in the usual manner of these things, it is not the whole
      story. As discussed in this article, it is becoming clear that the AMPK system is
      partly, but not entirely, responsible for the acute metabolic responses of muscle
      to acute exercise. It is particularly involved in the switch from the anaerobic
      metabolism of glycogen to oxidative metabolism of blood glucose and fatty acids.
      It also appears to be responsible for most, if not all, of the long-term
      metabolic adaptations to aerobic exercise (i.e., to endurance training),
      particularly the up-regulation of mitochondrial content and oxidative metabolism.
      Interestingly, this role is a reflection of the evolutionary origins of the
      kinase, because the homolog of AMPK in a single-celled eukaryote, the brewer's
      yeast Saccharomyces cerevisiae, is also involved in the switch from anaerobic to
      aerobic metabolism.

PMID- 14707765
TI  - Red blood cell-derived ATP as a regulator of skeletal muscle perfusion.
AB  - Blood flow to skeletal muscle is a complex process designed to provide adequate,
      yet not excessive, amounts of oxygen to meet the ever-changing metabolic needs of
      the tissue. To accomplish this goal, a mechanism must exist that couples the
      oxygen needs of the tissue with the oxygen delivery system. A number of
      mechanisms have been investigated that have focused primarily on the vessel or
      tissue supplied. However, because none of these was able to adequately explain
      the precision inherent in oxygen supply, we began to investigate the potential
      role of the mobile oxygen carrier itself, the red blood cell. This review will
      provide evidence in support of the idea that the red blood cell is able to both
      sense oxygen need and evoke changes in blood flow to meet that need. In this
      scheme, as a red blood cell enters a region of increased metabolic demand
      relative to supply, the fall in hemoglobin oxygen saturation evokes the release
      of ATP, found within the red blood cell in mM amounts. The released ATP binds to
      purinergic receptors located on the vascular endothelium and induces a
      vasodilation that is conducted upstream increasing oxygen supply to the region of
      tissue supplied by the vessel. Although this mechanism is likely only one
      component of a complex system, which precisely regulates blood flow, we suggest
      that it plays a vital role in the regulation of perfusion distribution within
      tissue.

PMID- 14707766
TI  - Contraction-induced injury run amok: an introduction.
AB  - Skeletal muscle has an amazing capacity to adapt to increased levels of physical
      activity. Adaptation is often preceded by contraction-induced injury. In most
      cases, the damage is repaired quickly, the muscle adapts, and becomes stronger
      and less fatigable. Diseased or deconditioned muscle is an exception; the
      response to increased functional demand, and the associated injury can be
      incomplete or even maladaptive. When and why is an adaptive response limited?
      This question will be addressed in the symposium papers following this brief
      introduction. The papers will discuss cellular, molecular, and immunological
      mechanisms that may be involved in impaired muscle adaptation.

PMID- 14707767
TI  - Targeting the immune system to improve ventilatory function in muscular
      dystrophy.
AB  - Skeletal muscle is a unique tissue whose function is dependent in great part on
      its ultrastructure. Repeated intense muscular contractions, especially those
      resulting in muscle lengthening, can lead to alterations in muscle structure
      (i.e., muscle damage) and subsequent decline in contractile force. The damage
      induced decline in contractile force can have a significant impact on exercise
      performance during an athletic performance. In some disease conditions such as
      Duchenne muscular dystrophy (DMD), the muscles are more vulnerable to contraction
      induced damage than normal muscle. In the case of the respiratory muscles, for
      example, the diaphragm, the consequences of muscle weakness secondary to damage
      are profound in that respiratory failure leading to premature death often ensues.
      In normal skeletal muscle, damage is followed by an inflammatory response
      involving multiple cell types that subsides after several days. This transient
      inflammatory response is a normal homeostatic reaction to muscle damage. In
      contrast, a persistent inflammatory response is observed in dystrophic skeletal
      muscle that leads to an altered extracellular environment, including an increased
      presence of inflammatory cells (e.g., macrophages) and elevated levels of various
      inflammatory cytokines (e.g., TNF-alpha, TGF-beta). The signals that lead to
      successful muscle repair in healthy muscle may promote muscle wasting and
      fibrosis in dystrophic muscle. Preliminary data indicate that immunosuppression
      in dystrophic (mdx) mice has beneficial effects on some indices of muscle
      dysfunction, thereby indicating that targeted immunosuppression may offer some
      promise in delaying the pathological progression of this insidious muscular
      disease.

PMID- 14707768
TI  - Regrowth of skeletal muscle atrophied from inactivity.
AB  - The current state of knowledge regarding regrowth of skeletal muscle after
      inactivity-induced atrophy is reviewed. Muscle regrowth is incomplete after
      hindlimb suspension in juvenile rats and after limb immobilization in old
      animals. The process of regrowth from immobilization-induced atrophy likely
      involves the reversal of directional changes in molecules producing muscle loss
      while initiating anabolic processes for regrowth of muscle mass. Unfortunately,
      the molecular mechanisms responsible for successful, or failed, muscle regrowth
      are not well understood. The purpose of the review is to provide current
      knowledge about the biology of muscle regrowth from inactivity-induced atrophy.

PMID- 14707769
TI  - Rat myocellular and perimysial intramuscular triacylglycerol: a histological
      approach.
AB  - PURPOSE: There is controversy as to the use of intramuscular triacylglycerol
      (IMTAG) during exercise and to whether endurance training increases its
      utilization, despite the various methodologies used to address these questions.
      We used a histological-morphometrical approach to study the relative contribution
      of the two compartments of IMTAG storage, intramyocellular, and perimysial
      adipocytes, during exercise in sedentary and endurance-trained rats. METHODS:
      After osmium impregnation, the soleus (SOL) and gastrocnemius (GAS) were studied
      under light and electron microscopy. IMTAG content (after Triton WR1339 treatment
      or not) and 14C-oleate incorporation into the muscles were studied. RESULTS: In
      GAS, training, but not exercise alone, decreased extramyocellular lipid (P <
      0.001 vs sedentary), an effect not found for SOL. Both muscles presented reduced
      lipid inclusion number (P < 0.001) and area (P < 0.05), immediately after
      exercise in sedentary and trained rats. For SOL, a greater number (P < 0.001 vs
      sedentary) of inclusions was found 24 h after exercise in trained rats. Triton
      WR1339 treatment decreased IMTAG content 12 h after exercise in SOL (but not in
      GAS), in sedentary (33%), and trained rats (52%). CONCLUSIONS: The multi
      analytical approach adopted allowed the discernment between the IMTAG
      compartments and provided evidence for an effect of training upon storage of
      lipid in perimysial adipocytes in rat gastrocnemius, as well as clearly showed
      that the IMTAG mobilized during submaximal exercise in sedentary and trained rats
      derives from intramyocellular lipid, both in SOL and GAS. Moreover, the
      reposition of these stores 12 h after exercise was shown to be different in GAS
      and SOL, as plasma triacylglycerol clearly contributed to the process only in the
      latter, possibly reflecting the differences in lipoprotein lipase activity in the
      muscles reported by others.

PMID- 14707770
TI  - Marathon running leads to partial exhaustion of ROS-generating capacity in
      leukocytes.
AB  - PURPOSE: The aim of the present study was to investigate the changes occurring in
      leukocyte levels of reactive oxygen species (ROS) and total blood plasma
      antioxidant capacity (TAS) as a result of a marathon/half-marathon race. METHODS:
      Fourteen men participating in the Oslo Marathon 2000 and 8 women and 8 men
      participating in the Oslo Half-Marathon 2001 were recruited to the study. Flow
      cytometry and the ROS-sensitive probe dihydroethidium (DHE) were used to study
      the intracellular levels of ROS in circulating leukocytes. Both basal ROS levels
      as well as the capacity of leukocytes to respond with ROS synthesis upon a
      defined in vitro stimulus, i.e., phorbol myristate acetate (PMA) was assessed
      before and immediately after the races. TAS was measured using the ABTS+
      reduction assay kit. RESULTS: The basal levels of ROS in leukocytes were either
      not significantly changed (men, 3-25% reduced) or reduced 33% (women, P < 0.01)
      as a result of the marathon/half-marathon race. After the marathon race, the
      capacity of leukocytes to produce ROS upon PMA stimulation was reduced, i.e., 6%
      (granulocytes) (P < 0.001) and 23% (monocytes) (P < 0.01) residual capacity
      compared with the prerace situation. A 22-30% reduction (P < 0.05) in monocyte
      ROS response was seen also as a result of the half-marathon race, whereas the
      granulocyte ROS response was maintained at the prerace level (19% (women) and 15%
      (men) reduction, NS)). TAS increased significantly (11-19%, P < 0.05) after both
      races. CONCLUSIONS: The present results indicate an exhaustion of leukocyte ROS
      generating mechanisms after prolonged strenuous exercise. This may partly explain
      the observation that athletes are more sensitive to attract infectious diseases
      if exposed to pathogenic micro-organisms during the immediate period after
      intensive physical activity.

PMID- 14707771
TI  - Endurance training delays age of decline in leg strength and muscle morphology.
AB  - PURPOSE: It has been reported that maximal strength peaks at approximately 30 yr
      of age, plateaus, and remains relatively stable for the next 20 yr, with an age
      related decline in strength becoming significant after age 50. Much of the
      research attributes this decrease in peak force to age-associated reductions in
      muscle mass, with a selective atrophy and reduction in Type II fiber area and
      number being the primary factors. The influence that chronic endurance training
      has upon age-associated changes in muscular strength and muscle morphology has
      been largely undetermined. The purpose of this investigation was to examine the
      influence of chronic endurance training and age on leg extensor strength, and
      muscle fiber size and type distribution. METHODS: Male master runners (N = 107,
      age range = 40-88 yr) were tested for maximal strength of the leg extensor
      muscles. A subgroup of 30 master athletes participated in muscle biopsy testing.
      The effects of age were addressed by subdividing the sample into five cohorts.
      RESULTS: Peak isokinetic concentric torque did not differ between age groups
      until after age 70 yr. Regression analysis revealed a significant (P < 0.05, r(2)
      = 0.1838) age-associated decrease in relative strength (N.m.kg(-1) lean body
      mass). Type I and Type II fiber area and distribution did not differ between age
      groups through the eighth decade. CONCLUSIONS: These data suggest that chronic
      endurance training can delay the age of significant decline in peak torque and
      changes in muscle morphology characteristics of the vastus lateralis.

PMID- 14707772
TI  - Physical activity in an Old Order Amish community.
AB  - One method to assess the impact of modern technology on physical activity is to
      examine a group whose lifestyle has not changed markedly in the last 150 yr. The
      Old Order Amish refrain from driving automobiles, using electrical appliances,
      and employing other modern conveniences. Labor-intensive farming is still the
      preferred occupation. PURPOSE: The purposes of this study were to characterize
      the physical activity (PA) levels in an Old Order Amish farming community and to
      examine measures of adiposity in this group. METHODS: Ninety-eight Amish adults
      (18-75 yr of age) in southern Ontario were studied. Anthropometric variables
      included height, weight, body mass index (BMI), and percent body fat (% BF).
      Participants were asked to wear an electronic pedometer for 7 d and to fill out a
      log sheet on which they recorded steps per day and physical activities. After 1
      wk, they returned the pedometers and log sheets and filled out the International
      Physical Activity Questionnaire. RESULTS: The average number of steps per day was
      18,425 for men versus 14,196 for women (P < 0.05). Men reported 10.0 h.wk-1 of
      vigorous PA, 42.8 h.wk-1 of moderate PA, and 12.0 h.wk-1 of walking. Women
      reported 3.4 h.wk-1 of vigorous PA, 39.2 h.wk-1 of moderate PA, and 5.7 h.wk-1 of
      walking. Men had higher levels of energy expenditure than women (P < 0.001). A
      total of 25% of the men and 27% of the women were overweight (BMI > or = 25), and
      0% of the men and 9% of the women were obese (BMI > or = 30). CONCLUSIONS: The
      Amish we studied had very high levels of physical activity, which may contribute
      to their low prevalence of obesity. This group probably represents an upper
      extreme for "lifestyle PA" in North America today.

PMID- 14707773
TI  - Physical activity levels and patterns of 9- and 15-yr-old European children.
AB  - PURPOSE: The purpose of this study was to assess physical activity levels and
      patterns from children participating in the European Youth Heart Study (EYHS).
      Very limited physical activity data exist that have been collected from
      representative samples of children and even fewer data collected where physical
      activity has been measured using objective methods. METHODS: Subjects were 2185
      children aged 9 and 15 yr from Denmark, Portugal, Estonia, and Norway. Physical
      activity data were obtained using MTI (formerly CSA) accelerometers. The primary
      outcome variable was established as the child's activity level (accelerometer
      counts per minute). Children wore the accelerometer for 3 or 4 d, which included
      at least 1 weekend day. RESULTS: Boys were more active than girls at age 9 (784
      +/- 282 vs 649 +/- 204 counts.min-1) and 15 yr (615 +/- 228 vs 491 +/- 163
      counts.min-1). With respect to time engaged in moderate-intensity activity,
      gender differences were apparent at age 9 (192 +/- 66 vs 160 +/- 54 min.d-1) and
      age 15 (99 +/- 45 vs 73 +/- 32 min.d-1). At age 9, the great majority of boys and
      girls achieved current health-related physical activity recommendations (97.4%
      and 97.6%, respectively). At age 15, fewer children achieved the guidelines and
      gender differences were apparent (boys 81.9% vs girls 62.0%). CONCLUSIONS:
      Accelerometers are a feasible and accurate instrument for use in large
      epidemiological studies of children's activity. Boys tend to be more active than
      girls, and there is a marked reduction in activity over the adolescent years. The
      great majority of younger children achieve current physical activity
      recommendations, whereas fewer older children do so-especially older girls.

PMID- 14707774
TI  - In vivo and noninvasive three-dimensional patellar tracking induced by individual
      heads of quadriceps.
AB  - PURPOSE: Unbalanced actions of the quadriceps components are closely linked to
      patellar mal-tracking and patellofemoral pain syndrome. However, it is not clear
      how individual quadriceps components pull and rotate the patella three
      dimensionally. The purpose of this study was to investigate in vivo and
      noninvasively patellar tracking induced by individual quadriceps components.
      METHODS: Individual quadriceps component was activated selectively through
      electrical stimulation at the muscle motor point, and the resulting patellar
      tracking was measured in vivo and noninvasively in 18 knees of 12 subjects. The
      in vivo and noninvasively patellar tracking was corroborated with in vivo
      fluoroscopy and in vitro cadaver measurements. RESULTS: Vastus medialis (VM)
      mainly pulled the patella first in the medial and second in the proximal
      directions and vastus lateralis (VL) pulled first in the proximal and second in
      the lateral directions. The oblique portion (VMO) of the VM pulled the patella
      mainly medially and the longus portion (VML) more proximally. Medial tilt was the
      major patellar rotation induced by VMO contraction at full knee extension. With
      the knee at the more flexed positions, the amplitude of patellar movement induced
      by comparable quadriceps contractions was reduced significantly compared to that
      at full knee extension, and VMO changed its main action from extending to flexing
      the patella. CONCLUSIONS: The medial and lateral quadriceps components moved the
      patella in rather different directions, and rotated the patella differently about
      the mediolateral tilt and mediolateral rotation axes but similarly in extension.
      The approach can be used to investigate patellar tracking in vivo and
      noninvasively in both healthy subjects and patients with patellofemoral disorder
      and patellar malalignment.

PMID- 14707775
TI  - Validation of the adult OMNI scale of perceived exertion for cycle ergometer
      exercise.
AB  - PURPOSE: Concurrent and construct validity of the OMNI-Cycle Scale of Perceived
      Exertion were examined using young adult women and men (18-32 yr). METHODS:
      Concurrent validity was established by correlating OMNI-Cycle Scale ratings of
      perceived exertion (RPE) with oxygen consumption (.VO2) and heart rate (HR)
      responses to a load-incremented cycle ergometer protocol. Construct validity was
      established by correlating RPE derived from the OMNI-Cycle Scale with RPE from
      the Borg (6-20) Scale. RPE, .VO2, and HR were measured during each exercise
      stage. RESULTS: The range of exercise responses across the incremental test for
      the female and male groups was .VO2 = 0.92-2.74 L.min-1, HR = 107.2-167.2
      beats.min-1, and OMNI Scale RPE-Overall, RPE-Legs, and RPE-Chest 1.0-9.1.
      Correlation/regression analyses indicated that RPE-Overall, RPE-Legs, and RPE
      Chest distributed as a positive linear function of both .VO2 and HR (r = 0.81 to
      0.95; P < 0.01). Undifferentiated and differentiated RPE-OMNI Scale distributed
      as a positive linear function of RPE-Borg Scale (r = 0.92 to 0.97; P < 0.01).
      ANOVA indicated that OMNI-Cycle RPE-Legs was higher (P < 0.01) than RPE-Chest at
      each exercise stage for both genders. CONCLUSION: Concurrent and construct
      evidence supports use of the OMNI Scale by adult women and men to estimate RPE
      during cycle exercise.

PMID- 14707776
TI  - Gender differences in perceived exertion during fatiguing knee extensions.
AB  - PURPOSE: To examine gender differences in knee extensor strength, fatigue, and
      perceived exertion during a single set of continuous dynamic knee extensor
      contractions. METHODS: Fifteen men and 15 women were evaluated for their one
      repetition maximum (1RM) during a single-leg, inertial knee extension with their
      right leg. All subjects then completed a single set of repeated knee extensions
      with a load equivalent to 50% of their 1RM to failure. Subjects lifted the weight
      by performing a knee extension, held the weight with the knee extended for 1-2 s,
      and then lowered the weight in a slow and controlled manner. Perceived exertion
      was measured after completion of each repetition, by viewing a modified Borg
      category-ratio (CR-10) scale. Perceived exertion responses were standardized
      across subjects via linear interpolation and power function modeling. The linear
      interpolated perceived exertion estimates were then examined for linear,
      quadratic, and cubic trends across the repetitions. RESULTS: Men lifted a
      significantly greater amount of mass than women, when corrected for body mass.
      Men and women did not differ significantly in the number of repetitions performed
      to failure. Women displayed significantly higher power function exponents for the
      perceived exertion response than men (0.72 +/- 0.16 and 0.57 +/- 0.16,
      respectively) and demonstrated statistically nonsignificant greater increases in
      perceived exertion than men across the repetitions. CONCLUSIONS: The major
      findings of this study indicated that: 1) men inherently possessed greater knee
      extensor strength than women; 2) submaximal fatiguing knee extensor performance
      did not differ between genders; 3) model selection had a significant impact on
      standardizing perceived exertion estimates; and 4) subtle gender differences in
      the perceived exertion response may have existed during submaximal, fatiguing
      resistance exercise.

PMID- 14707777
TI  - Cerebral cortical adaptations associated with visuomotor practice.
AB  - PURPOSE: Electroencephalographic (EEG) recordings were examined at the temporal
      (T3, T4) regions of the cerebral cortex in novice pistol shooters (N = 11) over a
      training period of 12-14 wk to determine changes in activation. Mean alpha power
      and its rate of change were hypothesized to increase in the left temporal region
      during aiming from early to late season as participants improved their accuracy
      and reduced cognitive effort. METHODS: Event-related alpha II power (ERAP; 11-13
      Hz) was examined over a 5-s period preceding the trigger pull during shooting
      (SH) and two control conditions (resting baseline, BL; and postural simulation,
      PS) at early (time 1), middle (time 2), and late (time 3) practice. RESULTS: Mean
      levels of ERAP increased at T3 from the beginning to the end of the training
      period during both SH and PS, but not BL, whereas no such change in mean level of
      ERAP was noted at T4 during any of the three conditions. The practice-related
      cortical adaptation during SH covaried with an increase in shooting percentage
      over the season. A higher rate of increase in ERAP during the 5-s aiming period
      of SH relative to that at PS and BL was also observed throughout training at both
      T3 and T4. Exploratory analysis of global power (sites F3, Fz, F4, C3, Cz, C4,
      P3, Pz, and P4) revealed that ERAP increased during SH from time 1 to time 3 at
      all sites except Fz and Pz, whereas only one site (C4) revealed an increase
      during BL. CONCLUSIONS: The reduction in cortical activity is likely due to
      sensorimotor integration and less cognitive effort due to automaticity.

PMID- 14707778
TI  - Measuring performance during the menstrual cycle: a model using oral
      contraceptives.
AB  - PURPOSE: The aim of the study was to use a low-dose oral contraceptive (OC) pill
      to generate consistent estrogen and progestogen concentrations and investigate
      the relationship between steroid hormone concentrations during the OC cycle and
      anaerobic performance. METHODS: Five female rowers taking a low-dose OC performed
      tests of anaerobic power (10-s all-out effort) and capacity (1000-m row) on the
      Concept IIC rowing ergometer at two time points in each of three OC cycles. These
      time points corresponded to high estrogen and high progestogen (pill day 16-18;
      TDH) and low estrogen and low progestogen (pill day 26-28; TDL). Blood samples
      were collected at rest and postexercise for the quantification of 17beta
      estradiol (E2), progesterone (P4), glucose, triglyceride, and lactate
      concentrations. RESULTS: Endogenous E2 and P4 concentrations were not
      significantly different between testing days or OC cycles (P > 0.05). Peak power
      output was higher (P < 0.05) and 1000-m rowing ergometer time faster (P < 0.05)
      at TDL. Pre- and postexercise glucose concentrations were increased (P < 0.05) at
      TDL, whereas rest and postexercise plasma triglyceride concentrations were
      significantly (P < 0.05) lower during this time. CONCLUSIONS: This study found
      that alterations in anaerobic performance throughout the OC cycle occurred with
      improved performances corresponding to low estrogen and progestogen
      concentrations. The OC provided a consistent hormonal milieu reducing inter- and
      intra-individual variations in sex steroids and standardized all performance and
      metabolic variables across each OC cycle tested. Given that OC use has a high
      prevalence among female athletes and provides a controlled hormonal environment,
      it serves as a good model in which the acute effects of female sex steroids on
      exercise performance can be studied.

PMID- 14707779
TI  - Annual changes of bone density over 12 years in an amenorrheic athlete.
AB  - PURPOSE: To link annual changes of bone mineral density (BMD) over 12 consecutive
      years to pharmacological intervention and to fluctuations of body mass and body
      composition in an amenorrheic athlete. METHODS: BMD of the lumbar spine (LS) and
      total proximal femur (PF) were measured using dual energy x-ray absorptiometry
      (DXA), every 11-13 months between ages 24.8 and 36.9 yr. Body composition was
      assessed every 3-4 yr from a whole body DXA scan. Body mass was recorded every 3
      months. For the first 5 yr of study, the subject used oral contraceptives (OC).
      For the subsequent 7 yr, she used estradiol skin patches (EP) with oral
      norethisterone. RESULTS: The first DXA scan (age 24.8 yr) revealed a low BMD at
      both LS and PF, with T-scores of -1.4 and -2.8, respectively. During the next 5
      yr, while adhering to OC, the BMD of her LS and PF declined by 9.8% and 12.1%,
      respectively. Concomitantly, her body mass fell from 45.1 to 41.4 kg, her body
      mass index (BMI) from 16.4 to 15.0 kg.m-2, and her percent body fat from 8.3 to
      <4.0%. While treated with EP and norethisterone (age 29.8-33.5 yr), her LS BMD
      gradually increased by 9.4%, despite a further 0.8 kg decline of body mass. From
      age 33.8 to 36.9 yr, voluntary weight gain (2-3 kg.yr-1; total: 8.1 kg) was
      accompanied by an increase of her PF BMD (16.9%), with no further increase at the
      LS. CONCLUSION: Changes of BMD at the total proximal femur reflected changes of
      body mass in this subject. At the lumbar spine, BMD declined with weight loss but
      increased in association with transdermal estradiol treatment in the absence of
      weight gain.

PMID- 14707780
TI  - Age-related declines in anaerobic muscular performance: weightlifting and
      powerlifting.
AB  - PURPOSE: One approach to studying the effects of aging on physiological
      functional capacity (PFC) in humans is to analyze the peak physical performance
      of trained athletes with increasing age. The primary aim of the present study was
      to determine weightlifting and powerlifting performance with increasing age in
      both men and women. METHODS: We performed a retrospective analysis of top age
      group weightlifting and powerlifting records compiled from the U.S. Weightlifting
      and U.S. Powerlifting Organizations. RESULTS: Regression analyses showed that in
      both men and women weightlifting and powerlifting performance declined
      curvilinearly and linearly, respectively. The rate and the overall magnitude of
      declines in performance with age were markedly greater (P < 0.05) in
      weightlifting than in powerlifting. The rates of age-related decline in muscular
      power were not different between upper body (bench press) and lower body (squat).
      Similarly, the age-related declines were not different between snatch and clean
      and jerk in weightlifting events. The magnitude of the declines with age was
      greater (P < 0.05) in women than in men in weightlifting; no such sex-related
      differences were observed in powerlifting performance. CONCLUSIONS: The findings
      in this cross-sectional study indicate that 1) peak anaerobic muscular power, as
      assessed by peak lifting performance, decreases progressively even from earlier
      ages than previously thought; 2) the overall magnitude of decline in peak
      muscular power appears to be greater in tasks requiring more complex and powerful
      movements; 3) the age-related rates of decline are greater in women than in men
      only in the events that require more complex and explosive power; and 4) upper-
      and lower-body muscular power demonstrate similar rate of decline with age.

PMID- 14707781
TI  - Optimal loading during two different leg-press movements in female rowers.
AB  - PURPOSE: The purpose of this study was to determine the optimal load for power
      during concentric only (CO) and stretch-shortening cycle (SSC) leg-press
      movements during the initial portion of the concentric phase as well as
      throughout the entire concentric phase in trained female rowers. METHODS: Thirty
      female rowers (age = 19.6 +/- 1.2 yr) were tested for strength (1RM), mean power
      (MP), peak power (PP), as well as power output at 50, 100, 150, and 200 ms (P50
      P200) during both CO and SSC leg-press movements and across six different loads
      (30-80% 1RM) on the Omnikinetic dynamometer. RESULTS: Split-split plot analysis
      indicated that MP and PP were maximized at approximately 60% 1RM in both CO and
      SSC movements. There were no significant differences in P50 and P100 across all
      loads for both CO and SSC. P150 was greatest at 30, 40, 50, and 60% 1RM for CO
      and SSC movements. P200 was maximized at 30, 40, and 50% 1RM during CO. P200 was
      maximized at 50, 60, and 70% 1RM during SSC. CONCLUSIONS: There was no difference
      in the optimal loads for MP (40, 50, and 60% 1RM) and PP (50, 60, and 70% 1RM)
      between CO and SSC movements. An enhancement of power during the initial 200 ms
      of the concentric phase of SSC movements was observed. Greater time to reach PP
      was the reason for the enhancement in PP output observed in CO movements. The CO
      training regimen associated with the sport of rowing also may have lessened the
      effect of the SSC.

PMID- 14707782
TI  - Assessment of cardiovascular regulation during head-up tilt and suspension in
      swimmers.
AB  - PURPOSE: The purpose of the present study was to compare cardiovascular responses
      in competitive swimmers with those in track and field (T and F) athletes during
      head-up tilt with engagement of the antigravity muscles in the lower extremities
      and during passive head-up suspension without the engagement of the antigravity
      muscles. METHODS: Blood pressure and heart rate during head-up tilt were compared
      among T and F athletes (N = 11), competitive swimmers (N = 15), and untrained
      subjects (N = 11). Moreover, stroke volume, cardiac output, and total peripheral
      resistance during head-up tilt and head-up suspension were also measured in T and
      F athletes and competitive swimmers. RESULTS: The heart rate increased
      significantly in all subject groups during head-up tilt; however, the MBP
      decreased in untrained subjects but did not change significantly in T and F
      athletes or competitive swimmers. Moreover, the DBP did not change significantly
      in untrained subjects or T and F athletes but increased significantly in
      swimmers. As with the head-up tilt, during the head-up suspension, the SBP
      decreased significantly and the heart rate increased significantly in both types
      of athletes, though the MBP decreased significantly. The ratios of decrease in
      stroke volume and cardiac output were significantly larger in swimmers than in T
      and F athletes during head-up tilt, but no significant difference was noted
      during head-up suspension. In T and F athletes, the ratios of decrease in stroke
      volume and cardiac output were significantly larger during head-up suspension
      than during head-up tilt, but no significant difference was noted in swimmers.
      CONCLUSION: The action of the antigravity muscles on cardiovascular regulation
      during upright standing is smaller in competitive swimmers than in T and F
      athletes.

PMID- 14707783
TI  - The effect of dehydration on wrestling minimum weight assessment.
AB  - Given that some wrestlers arrive for minimum weight (MW) testing in a dehydrated
      condition, it is important to understand the effects of dehydration on MW
      assessment methods. PURPOSE: To determine the effect of dehydration on the
      assessment of MW by three-site skinfolds with the Lohman formula (SF), leg-to-leg
      bioelectrical impedance analysis (BIA), and multifrequency bioelectrical
      impedance spectroscopy (BIS) compared with a four-component (4C) criterion.
      METHODS: Twenty-two male collegiate wrestlers (mean +/- SD, age: 19.9 +/- 1.4 yr,
      height: 174.0 +/- 6.8 cm, body mass: 77.4 +/- 9.1 kg) had their body composition
      assessed by the 4C criterion, hydrostatic weighing (HW), SF, BIA, and BIS in
      euhydration (EUH) and dehydration (DEH). Subjects dehydrated 2-5% of body weight
      through fluid restriction and exercise in a hot environment. RESULTS: In EUH, the
      total error (TE) for HW (1.75 kg) and SF (2.15 kg) were not significantly
      different, but the TE for HW and SF methods were significantly lower than the TE
      for both BIS (3.68 kg) and BIA (3.77 kg). In DEH, SF, BIA, and BIS methods had a
      TE approaching or exceeding 4 kg (8.8 lb). Dehydration increased the TE for SF
      and BIA through an artificial lowering of body weight and for BIS by an increased
      error in intracellular water prediction. CONCLUSION: Acute thermal dehydration
      violates assumptions necessary for the accurate and precise prediction of MW by
      SF, leg-to-leg BIA, and multifrequency BIS.

PMID- 14707784
TI  - Physiological profile and activity pattern of young soccer players during match
      play.
AB  - PURPOSE: The purpose of this study was to examine aerobic demands and activity
      patterns during match play in young soccer players with respect to competition
      level, age, and biological maturity. METHODS: Ten nonelite players (NbP) and nine
      elite players (EbP) in their early puberty (12 yr), and seven elite players (EeP)
      in their late puberty (14 yr) were studied. Heart rate (HR) and activity pattern
      were recorded during match play, whereas corresponding .VO(2) and HR values were
      obtained during submaximal and maximal treadmill tests in the laboratory. The
      maturity status was assessed from testicular volume. RESULTS: No difference in
      .VO(2max) was observed between the nonelite and the elite players in the
      beginning of puberty (58.7 +/- 5.3 vs 58.6 +/- 5.0 mL O(2).min-1.kg(-1)), whereas
      the elite players in the end of puberty were significantly more fit (63.7 +/- 8.5
      mL O(2).min(-1).kg(-1)). During match play, a higher HR was recorded in the elite
      players in the beginning of puberty than their nonelite counterparts, whereas the
      two elite groups showed the same HR responses (HR 1st half/2nd half-NbP: 162/157;
      EbP: 177/174; EeP: 178/173). The elite players in the end of puberty thus
      performed a higher absolute and relative .VO(2) (.VO(2).min(-1) and mL O(2).min(
      1).kg(-1)) compared with the nonelite players during both halves, corresponding
      to more time spent in standing/walking in the nonelite group. The elite players
      in the end of puberty showed higher absolute .V(O2) values during match play than
      the young elite players but identical relative aerobic loads. It seems that the
      midfield/attack group had the highest absolute .VO(2max) and was performing at
      the highest HR during the matches. CONCLUSION: The present study shows that young
      soccer players are highly specialized both according to playing level and
      position on the field.

PMID- 14707785
TI  - Are neutrophils really involved in exercise-induced oxidative stress?

PMID- 14707786
TI  - Risk associated HIV-1 cross-clade resistance of whole peripheral blood
      mononuclear cells from exposed uninfected individuals with wild-type CCR5.
AB  - Highly HIV exposed, persistently uninfected individuals (EUs) may hold clues to
      the generation of effective vaccine induced acquired immunity against HIV, and
      considerable effort has been devoted to detecting and characterizing HIV specific
      immune responses in EU cohorts. When searching for such clues, it is important to
      exclude individuals with genetically determined absence of receptors, as this
      protective mechanism could not be induced by HIV specific vaccines. Homozygosity
      for the DeltaC32 mutation of CCR5 prevents R5 HIV infection, independent of any
      virus-specific immune responses that may be acquired by exposure, while
      heterozygosity influences susceptibility to low level exposure. Reports on the in
      vitro susceptibility of EU cells compared to controls have been conflicting.
      Therefore, we studied 14 EUs with homozygous wild type CCR5, using a newly
      developed in vitro challenge assay (IVCA) to measure the magnitude and breadth of
      resistance to infection among EUs. CD8+ cells were relatively increased compared
      to controls, and were largely responsible for resistance to challenge, which
      depended on dose of virus inoculum, and extended across clades. Consistent with
      some EU cohort studies, resistance waned among individuals who reduced their high
      risk behavior.

PMID- 14707787
TI  - Magnetic resonance imaging of activated proliferating rhesus macaque T cells
      labeled with superparamagnetic monocrystalline iron oxide nanoparticles.
AB  - Imaging of adoptively transferred cells in vivo by magnetic resonance imaging
      (MRI) could provide important information on disease-related patterns of
      lymphocyte homing in nonhuman primate models of AIDS. As a preliminary study to
      assess the feasibility of visualizing activated rhesus T cells by MRI, anti
      CD3/CD28-expanded CD4+ T lymphocytes were labeled in vitro with monocrystalline
      iron oxide nanoparticles (MION). Intracellular incorporation of MION was
      determined by transmission electron microscopy (TEM) and inductively coupled
      plasma mass spectrography (ICP-MS). Pretreatment with colchicine did not affect
      MION labeling, suggesting that cellular uptake of MION occurred by adsorptive
      pinocytosis or receptor-mediated endocytosis. TEM analysis revealed that MION
      were intracellularly compartmentalized exclusively in the cytoplasm and did not
      cause any measurable physiologic effects on T-cell function, including viability,
      proliferation, synthesis of select cytokines (interleukin [IL]-2, IL-4, IL-6, IL
      10, tumor necrosis factor-alpha, and interferon-gamma), activation antigens (CD25
      and CD69), adhesion molecules (alpha4beta7 and CD49d), and susceptibility to in
      vitro infection with simian immunodeficiency virus mac239. A sensitivity of 0.05%
      (1 MION-labeled T cell in 2000 unlabeled cells) could be achieved using T2
      weighted gradient echo imaging. Furthermore, under these experimental conditions,
      the MRI signal did not decrease in proliferating MION-labeled CD4+ T cells over a
      period of 120 hours. These results indicate that intracellular labeling with MION
      can be a useful technique for noninvasively monitoring trafficking patterns of
      adoptively transferred leukocyte subsets in real-time by MRI in nonhuman primate
      models of AIDS.

PMID- 14707788
TI  - The NEAT study: a 48-week open-label study to compare the antiviral efficacy and
      safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1
      infected patients.
AB  - OBJECTIVE: To compare the efficacy, durability, and tolerability of GW433908
      (908), 1400 mg twice-daily (BID), with nelfinavir (NFV), 1250 mg BID. METHODS:
      This was an international, multicenter, randomized, open-label study (NEAT) in
      antiretroviral therapy (ART)-naive HIV-infected adults with plasma HIV-1 RNA
      (vRNA) at screening > or =5000 copies/mL (c/mL). Patients were randomly assigned
      to 908 or NFV (2:1) for a minimum of 48 weeks, with a background of abacavir
      (ABC) and lamivudine (3TC). RESULTS: A total of 166 patients received randomized
      treatment with 908 BID and 83 received NFV BID. The population was diverse with
      regard to race and gender (76% Hispanics and blacks, 31% female) and had advanced
      HIV disease at screening (45% had vRNA >100,000 c/mL, 48% had CD4 cell counts
      <200 cells/mm3, 20% had a history of Centers for Disease Control class C events).
      After 48 weeks of study by an intention-to-treat rebound or discontinuation =
      failure analysis, a greater proportion of patients in the 908 BID group (66%)
      than the NFV BID group (51%) achieved vRNA <400 c/mL. Furthermore, more patients
      with screening vRNA >100,000 c/mL (67 vs. 35%) or CD4 <50 cells/mm3 (48 vs. 24%)
      achieved undetectable viral loads taking 908 BID compared with NFV BID,
      respectively. Favorable immunologic responses were observed for both groups.
      Diarrhea, which was more common in the NFV BID group (18 vs. 5%), was the only
      drug-related grade 2-4 adverse event with a significant difference (P = 0.002) in
      incidence between groups. CONCLUSION: Administration of 908 BID resulted in a
      potent and sustained antiretroviral response, notably in ART-naive patients with
      advanced HIV disease. GW433908 was generally well tolerated and provides a
      convenient dosing option without food or fluid restrictions.

PMID- 14707789
TI  - Intensification of antiretroviral therapy accelerates the decay of the HIV-1
      latent reservoir and decreases, but does not eliminate, ongoing virus
      replication.
AB  - This study evaluated whether intensification of standard antiretroviral therapy
      with abacavir, with or without efavirenz, leads to better viral suppression and
      acceleration of the rate of HIV-1 decay. Ten HIV-1-infected individuals were
      enrolled in a prospective, open-label study and received standard, combination
      antiretroviral therapy with either 3 or 4 agents. The rate of decay of the HIV-1
      latent reservoir and the frequency of intermittent viremia were compared between
      5 patients who underwent treatment intensification and 5 control subjects with
      comparable baseline characteristics. When compared with control patients, the
      median half-life (t1/2) of the latent reservoir decreased from 31 to 10 months (P
      = 0.016) in subjects who had treatment intensification. The frequency of
      intermittent viremia/year also decreased in 4 of 5 individuals following
      intensification (2.4/y vs. 0.8/y). These data suggest that ongoing virus
      replication during standard antiretroviral therapy is due, in part, to the
      inadequate antiviral potency of current regimens. Despite better viral
      suppression, treatment intensification did not completely block viral
      replication, as evidenced by continuing intermittent viremia in some individuals.
      Additional studies are needed to understand the host- and pathogen-related
      determinants of incomplete pharmacologic control of HIV-1 replication.

PMID- 14707790
TI  - Patterns of marijuana use among patients with HIV/AIDS followed in a public
      health care setting.
AB  - OBJECTIVES: To examine prevalence and patterns of smoked marijuana and perceived
      benefit and to assess demographic and clinical factors associated with marijuana
      use among HIV patients in a public health care setting. METHODS: Participants (n
      = 252) were recruited via consecutive sampling in public health care clinics.
      Structured interviews assessed patterns of recent marijuana use, including its
      perceived benefit for symptom relief. Associations between marijuana use and
      demographic and clinical variables were examined using univariate and
      multivariate regression analyses. RESULTS: Overall prevalence of smoked marijuana
      in the previous month was 23%. Reported benefits included relief of anxiety
      and/or depression (57%), improved appetite (53%), increased pleasure (33%), and
      relief of pain (28%). Recent use of marijuana was positively associated with
      severe nausea (odds ratio [OR] = 4.0, P = 0.004) and recent use of alcohol (OR =
      7.5, P < 0.001) and negatively associated with being Latino (OR = 0.07, P <
      0.001). No associations between marijuana use and pain symptoms were observed.
      CONCLUSIONS: The findings suggest that providers be advised to assess routinely
      and better understand patients' "indications" for self-administration of
      cannabis. Given the estimated prevalence, more formal characterization of the
      patterns and impact of cannabis use to alleviate HIV-associated symptoms is
      warranted. Clinical trials of smoked and noncombustible marijuana are needed to
      determine the role of cannabinoids as a class of agents with potential to improve
      quality of life and health care outcomes among patients with HIV/AIDS.

PMID- 14707792
TI  - Evaluation of an emergency department referral system for outpatient HIV testing.
AB  - BACKGROUND: Undiagnosed HIV infection is prevalent among patients who present to
      urban emergency departments (EDs). Providing appropriate counseling, testing, and
      follow-up in the ED is difficult. The aim of this study was to evaluate the
      effectiveness of a referral-based outpatient HIV testing system for patients
      referred from the ED. METHODS: This was a prospective cohort study performed at
      an urban teaching hospital. Consecutive patients referred from the emergency
      department (ED) for outpatient HIV testing were enrolled. Data were collected
      from each patient's ED record and HIV clinic record, if applicable. RESULTS: Of
      the 586 referrals made from our ED, 494 (84%) met inclusion criteria. Only 56
      patients (11%, 95% CI: 9-15%) arrived at the HIV clinic and completed pretest
      counseling. Of these, 51 (91%, 95% CI: 80-97%) tested negative for HIV, 4 (7%,
      95% CI: 2-17%) tested positive for HIV, and 1 (2%, 95% CI: 0-10%) refused the
      test. CONCLUSIONS: This referral system was ineffective at identifying
      unrecognized HIV infection due to poor adherence. Changes in the structure of the
      referral system or the use of point-of-care testing in the ED may improve the
      ability to detect HIV infection in this setting.

PMID- 14707791
TI  - Differences in HIV disease progression by injecting drug use in HIV-infected
      persons in care.
AB  - BACKGROUND: In the United States and many Western countries, injecting drug use
      continues to be an important cause of HIV infection. This has important clinical
      and public health implications if injecting drug users (IDUs) have greater
      barriers to antiretroviral effectiveness than other risk groups. We assessed if
      there were differences between HIV-infected IDUs and non-IDU patients in the
      development of AIDS-defining illnesses (ADIs) from the time the patients started
      their first combination antiretroviral therapy (CART) regimen. METHODS: We
      compared clinical outcomes for IDU patients (n = 827) with those for non-IDU
      patients (n = 1314) after they started CART. We controlled for financial access,
      because all patients had access to CART through insurance or a drug assistance
      program. The incidence (number of ADI cases per 100 person-years) was compared
      for IDUs and non-IDUs from 1995 through 2002. Incidence ratios were calculated
      for IDUs compared with non-IDUs. Risk factors for development of ADIs were
      assessed using negative binomial regression. RESULTS: From 1995-1996 to 2001
      2002, there was a decline in ADI incidence among IDUs from 31.9 to 16.2 cases per
      100 person-years of follow-up. Over the same time, there was a decline in ADI
      incidence among non-IDUs from 37.0 to 9.7 cases per 100 person-years. The
      incidence ratio (incidence among IDUs compared with that among non-IDUs)
      increased from 0.87 (95% confidence interval [CI], 0.65-1.15) to 1.67 (95% CI,
      1.25-2.18) from 1995-1996 to 2001-2002. By negative binomial regression, the
      incidence ratio for ADIs among IDUs versus non-IDUs increased to 1.45 (95% CI,
      1.21-1.75), after 1998, adjusting for differences in demographic, clinical, and
      treatment factors. CONCLUSIONS: The relative incidence of ADIs among IDUs with
      access to treatment increased approximately 50% compared with non-IDUs since
      1999. This suggests greater barriers to the effective use of CART for IDUs,
      resulting in a higher individual and public health burden of clinical HIV
      disease. It will be important to understand reasons for this growing difference
      and to implement appropriate interventions to improve the effective use of CART
      for IDUs.

PMID- 14707793
TI  - HIV-positive injection drug users who leave the hospital against medical advice:
      the mitigating role of methadone and social support.
AB  - BACKGROUND: Leaving the hospital against medical advice has been associated with
      increased morbidity and readmission. Factors associated with the risk of leaving
      against medical advice among HIV/AIDS patients or injection drug users have not
      been examined in detail. OBJECTIVES: To examine the clinical and social factors
      associated with leaving against medical advice (AMA) from a specialized HIV/AIDS
      ward among patients who reported a history of injection drug use. METHODS: All
      patients with a history of injection drug use admitted to the HIV/AIDS ward at
      St. Paul's Hospital, Vancouver, British Columbia (the largest specialized
      HIV/AIDS hospital ward in Canada) between April 1997 and October 2000 were
      reviewed retrospectively. A multivariate logistic regression model utilizing a
      generalized estimating equation algorithm identified factors associated with
      leaving the hospital AMA. RESULTS: Of the 1056 hospital admissions to the
      HIV/AIDS ward by patients with a history of injection drug use, 263 (24.9%)
      resulted in leaving the hospital AMA. Independent positive predictors of leaving
      AMA included recent injection drug use (adjusted odds ratio [AOR] = 2.08, 95%
      confidence interval [CI]: 1.41-3.07) and aboriginal ethnicity (AOR = 1.55, 95%
      CI: 1.05-2.28). Discharge AMA was also more likely to occur on weekends (AOR =
      2.27, 95% CI: 1.49-3.48) and on days when social assistance payments were issued
      (AOR = 2.95, 95% CI: 1.70-5.10). Factors that independently reduced the odds of
      hospital discharge AMA included in-hospital methadone use (AOR = 0.49, 95% CI:
      0.32-0.76), social support (AOR = 0.33, 95% CI: 0.21-0.51), and older age (per 10
      year increment, AOR = 0.56, 95% CI: 0.43-0.73). CONCLUSIONS: Among HIV-positive
      patients with a history of injection drug use, the odds of leaving the hospital
      AMA were reduced for subjects who received inpatient methadone treatment, were of
      older age, or had social supports. Addiction treatment and interventions that
      enhance social supports in marginalized populations at risk for hospital
      discharge AMA should be further explored.

PMID- 14707794
TI  - Personal risk perception, HIV knowledge and risk avoidance behavior, and their
      relationships to actual HIV serostatus in an urban African obstetric population.
AB  - One quarter of pregnant women in Zambia are infected with HIV. Understanding how
      knowledge of HIV relates to personal risk perception and avoidance of risky
      behaviors is critical to devising effective HIV prevention strategies. In
      conjunction with a large clinical trial in Lusaka, Zambia, we surveyed postpartum
      women who had been tested for HIV but did not know their status before undergoing
      the questionnaire. Of 858 women for whom complete data were available, 248 (29%)
      were HIV infected. Women 22 years of age or older (adjusted odds ratio [AOR],
      1.7; 95% confidence interval [CI], 1.1-2.5), women reporting > or =2 sexual
      partners in their lifetime (AOR, 1.8; 95% CI, 1.3-2.5), and women reporting a
      history of a sexually transmitted infection (AOR, 2.7; 95% CI, 1.7-4.3) were more
      likely to be HIV infected. Having had > or =2 lifetime sexual partners was a
      marker for perception of high personnel risk for HIV infection (AOR, 1.5; 95% CI,
      1.1-2.1). However, there was no relationship between perceived risk of HIV
      infection and actual HIV status. In fact, 127 (52%) of 245 women who stated that
      they were at no or low risk for HIV infection were HIV infected. Living in an
      area of high HIV seroprevalence like Zambia seems to be the greatest risk factor
      for infection in unselected pregnant women. Before significant inroads can be
      made in decreasing the incidence of HIV infection among pregnant women,
      population-based strategies that involve men must be implemented.

PMID- 14707795
TI  - Mobility, sexual behavior, and HIV infection in an urban population in Cameroon.
AB  - Several studies, notably from rural areas, have shown an association between
      mobility and HIV infection. However, reasons for this association are poorly
      documented. In this study, we examined the relationship between mobility, sexual
      behavior, and HIV infection in an urban population of Cameroon. A representative
      sample of 896 men and 1017 women were interviewed and tested for HIV infection
      and other sexually transmitted infections in Yaounde in 1997. Mobile and
      nonmobile people were compared with respect to sociodemographic attributes, risk
      exposure, condom use, and prevalence of HIV infection, using descriptive
      statistics and multivariate logistic regression. Seventy-three percent of men and
      68% of women reported at least 1 trip outside of Yaounde in the preceding 12
      months. Among men, the prevalence of HIV infection increased with time away from
      town. Men who declared no absence were 5 times less likely to be infected than
      were those away for >31 days (1.4% vs. 7.6%, respectively; adjusted odds ratio,
      0.23; 95% confidence interval, 0.07-0.82). Furthermore, mobile men reported more
      risky sexual behaviors (ie, more partners and more one-off contacts). For women,
      the pattern was less clear: differences in the prevalence of HIV infection were
      less marked for nonmobile than for mobile women (6.9% vs. 9.8%, respectively; P >
      0.1). This study suggests that characteristics of male mobility may be an
      important feature of the HIV epidemic in Cameroon.

PMID- 14707796
TI  - Infant feeding practices of women in a perinatal HIV-1 prevention study in
      Nairobi, Kenya.
AB  - OBJECTIVE: To determine feeding practices and nutritional status of infants born
      to HIV-1-infected women. METHODS: Feeding plans and practices were evaluated by
      questionnaires and focus group discussions. Infants were weighed at 1 and 6 weeks
      and tested for HIV-1 at 6 weeks. RESULTS: Of 128 women seen after delivery, 111
      completed the study. Mothers who planned to breast feed were more likely to feed
      their infants as planned (86% vs. 55%; P < 0.001). Women opted to breast feed due
      to financial constraints, partner influence, and fear of losing confidentiality.
      Women who reported that their partners were willing to have HIV-1 testing were
      less likely to be breast feeding at 6 weeks (odds ratio [OR] = 0.3, 95%
      confidence interval [CI]: 0.1-0.8; P = 0.01). At 6 weeks, more infants were mixed
      fed (31% vs. 21%; P = 0.05) than at 1 week. Lower infant weight at 6 weeks was
      associated with not breast feeding (P = 0.001), HIV-1 infection (P = 0.05), birth
      weight <3000 g (P = 0.01), maternal employment (P = 0.02), and paying <$12.5 per
      month in house rent (among infants not breast fed; P = 0.05). CONCLUSIONS:
      Replacement feeding was difficult, particularly without partner support in HIV-1
      testing. Mixed feeding was common and increased by 6 weeks. Mothers of low
      socioeconomic status who opt not to breast feed require support to avoid
      nutritional compromise of infants.

PMID- 14707797
TI  - Predictors of self-reported HIV infection among drug injectors in Ukraine.
AB  - OBJECTIVE: To identify characteristics, including current high-risk drug and sex
      behaviors, associated with self-reported HIV infection among injection drug users
      (IDUs) in Ukraine. DESIGN: Targeted sampling of IDUs from Kiev, Odessa, and
      Makeevka/Donetsk, Ukraine. METHODS: From June through August 2002, 100 IDUs from
      each site were recruited through street outreach, including 212 who had
      previously been tested for HIV and knew their serostatus. Subjects were
      administered a standardized computer-assisted interview assessing HIV-related
      drug and sex risk behaviors and history of HIV testing. RESULTS: Twenty six
      percent of the 212 participants reported they were HIV-positive. Univariate
      followed by multiple logistic regression analyses were used to identify factors
      associated with HIV infection. In the 30-day period before their interview, HIV
      infected IDUs were significantly more likely to have injected with a needle
      previously used by another injector without disinfecting, frontloaded and/or
      backloaded, and shared the drug solution from a common container. In addition,
      they had higher prevalence rates for hepatitis B virus and hepatitis C virus than
      those not infected with HIV. On the other hand, they were more likely to have
      reported no sex partners and, if sexually active, more likely to have used a
      condom. CONCLUSION: The high HIV seroprevalence among IDUs in Ukraine, combined
      with their continued engagement in needle-related risk behaviors, assures the
      continuance of the epidemic in this region, a region that is the epicenter of HIV
      in Europe.

PMID- 14707798
TI  - Estimation of annual HIV transmission rates in the United States, 1978-2000.
AB  - The HIV/AIDS epidemic in the United States generally has been characterized by
      AIDS case incidence and AIDS-associated death rates; in a more limited fashion,
      the epidemic has also been described by AIDS prevalence; population-specific HIV
      prevalence; and HIV incidence statistics. However, HIV transmission rate
      information (i.e., the rate of transmission from persons living with HIV to HIV
      seronegative persons) has received relatively little attention. The purpose of
      the present paper is to estimate the annual HIV transmission rate (from HIV
      seropositive to HIV-seronegative persons) in the United States for the time
      period 1978-2000 and to discuss the practical utility of the findings. Using as
      input annual AIDS-associated deaths and HIV incidence (both variables, especially
      the latter, contain some element of uncertainty), the model described here finds
      that HIV transmission rates have dropped dramatically in the United States since
      the beginning of the epidemic and stayed approximately between 4.00-4.34% during
      the 1990s. This implies a programmatic success in that for more than roughly 95%
      of persons living with HIV in any given year, no HIV transmission occurs.
      Research is urgently needed to fully understand the circumstances that allow the
      remaining instances of HIV transmission to take place; moreover, serostatus
      appropriate HIV-related services are needed to disrupt these remaining instances
      of transmission.

PMID- 14707799
TI  - Does name-based HIV reporting deter high-risk persons from HIV testing? Results
      from San Francisco.
AB  - OBJECTIVE: Name-based HIV reporting has been recommended as a method to track the
      HIV epidemic but may deter or delay at-risk persons from HIV testing. Previous
      studies of a deterrent effect of HIV reporting were not conducted in areas with
      high HIV infection rates and politically active populations. METHODS: In a cross
      sectional survey, men who have sex with men (MSM) recruited from gay bars,
      heterosexuals recruited from the sexually transmitted disease clinic, and
      injection drug users (IDUs) recruited from street venues were administered a face
      to-face anonymous questionnaire. RESULTS: Ninety-four percent of the 118 MSM, 76%
      of the 99 heterosexuals, and 97% of 105 IDUs surveyed were tested. Six percent of
      MSM, 9% of heterosexuals, and none of the IDUs correctly identified California's
      HIV reporting regulations. Of the 75 (25%) participants who thought California
      had a name-based HIV reporting system, 2 were never tested and 23 had not been
      tested in the past 12 months. None of those who had never been tested and 2 of
      those who had not been tested in the past 12 months cited fear of being reported
      as a reason for not testing recently. CONCLUSION: Fear of reporting is an
      infrequently cited reason for deterring or delaying testing.

PMID- 14707801
TI  - Impact of resistance testing ordering guidelines on rates of wild-type virus
      detection among patients for whom highly active antiretroviral therapy fails.

PMID- 14707800
TI  - The effect of nevirapine on the pharmacokinetics of indinavir/ritonavir 800/100
      mg BID.

PMID- 14707802
TI  - Gynecomastia, lipodystrophy syndrome, and dyslipidemia occurring or worsening
      during antiretroviral regimens other than protease inhibitor-based ones.

PMID- 14707803
TI  - Mammography saves lives--or does it?

PMID- 14707808
TI  - The beginning of the end of Medicare.

PMID- 14707810
TI  - Controlled-release oxycodone.

PMID- 14707811
TI  - The top 10 myths about Medicare.

PMID- 14707812
TI  - Three tales of love.

PMID- 14707813
TI  - The vagina dialogues: do you douche?

PMID- 14707814
TI  - Acknowledging the 'elephant': communication in palliative care.

PMID- 14707815
TI  - Emergency: family-centered care in the ED.

PMID- 14707816
TI  - Bar codes and drug administration.

PMID- 14707817
TI  - Handle with care.

PMID- 14707818
TI  - Delays in seeking MI treatment.

PMID- 14707820
TI  - Nurturing the children of Chernobyl: an Irish nurse shares her summers with
      children from Belarus. Interview by Julia Freeman.

PMID- 14707821
TI  - Actively preventing injury: avoiding back injuries and other musculoskeletal
      disorders among nurses.

PMID- 14707822
TI  - Focal inner retinal hemorrhages in patients with drusen: an early sign of occult
      choroidal neovascularization and chorioretinal anastomosis.
AB  - PURPOSE: To present evidence that superficial retinal hemorrhage in the macula of
      patients with age-related macular degeneration (ARMD) may be an early sign of
      occult chorioretinal anastomosis (OCRA) and type 1 occult choroidal
      neovascularization (OCNV). METHODS: Retrospective follow-up study of 16 patients
      presenting with a small focal area of superficial retinal hemorrhages and drusen
      in the juxtafoveolar area in 24 eyes. RESULTS: OCRA and OCNV occurred in an older
      subset of patients with ARMD (mean age, 75 years). Of 22 eyes with the early
      stages of chorioretinal anastomosis (CRA), 18 had evidence of a piggyback
      neovascular complex, with the smaller subsensory retinal type 2 complex lying
      anterior to the larger subretinal pigment epithelial type 1 complex. At initial
      presentation, three patients had OCRA and OCNV bilaterally, and three patients
      had large disciform cicatricial lesions with overt CRA in the fellow eye. Nine
      patients had one or more laser photocoagulation treatments for early stages of
      CRA. Only one patient maintained visual acuity of better than 20/200 for >1 year.
      At the last follow-up, 24 of 26 eyes with CRA had visual acuity of 20/200 or
      less. CONCLUSION: Superficial retinal hemorrhage in the paracentral area of
      patients with drusen is the earliest sign of OCRA and OCNV. Fluorescein
      angiography and indocyanine green angiography are important in detecting the dual
      nature of the subretinal neovascular network. Photocoagulation and photodynamic
      treatment is usually unsuccessful in preserving central vision.

PMID- 14707823
TI  - Photodynamic therapy for chronic central serous chorioretinopathy.
AB  - PURPOSE: To determine whether photodynamic therapy (PDT) is effective for
      treatment of chronic central serous chorioretinopathy (CSC). METHODS: Sixteen
      eyes with chronic CSC and macular detachment documented by optical coherence
      tomography (OCT) received PDT guided by indocyanine green (ICG) angiography
      according to the parameters outlined in the TAP Study. One or more laser spots
      were applied to the areas of choroidal vascular hyperpermeability that
      corresponded to retinal pigment epithelium decompensation. Patients were observed
      for 6 to 12 months. Two PDT sessions 1 month apart were performed on 2 eyes.
      Examinations included visual acuity measurement, fundus biomicroscopy,
      fluorescein and ICG angiography, and OCT. RESULTS: Macular exudation resolved
      completely in 13 eyes (81%) and partially regressed in 3. Choriocapillaris
      hypoperfusion was shown by ICG angiography for several months at the site of PDT
      application. Visual acuity improved 1 to 4 lines in 11 eyes and was unchanged in
      5 eyes. CONCLUSIONS: ICG-guided PDT performed according to the parameters
      outlined by the TAP Study seems effective for treating chronic CSC. Further
      studies are needed to verify treatment safety and the time and rate of
      recurrences.

PMID- 14707824
TI  - Possible benefits of triamcinolone-assisted pars plana vitrectomy for retinal
      diseases.
AB  - PURPOSE: To study the advantages and complications of triamcinolone acetonide
      (TA)-assisted pars plana vitrectomy (PPV) for various retinal diseases. METHODS:
      This report is an interventional case series and nonrandomized study. One hundred
      seventy-seven eyes from 158 patients underwent PPV with or without TA. Group
      TA(+) consisted of 94 eyes and group TA(-) consisted of 83 eyes. The improvement
      in vision and postoperative complications were prospectively studied. RESULTS:
      Sixty-two percent of the eyes in group TA(+) and 49% of the eyes in group TA(-)
      had improved vision after surgery (P = 0.34). Twelve eyes in group TA(+) and 12
      eyes in group TA(-) had an intraocular pressure higher than 21 mmHg after the
      operation, with no statistically significant difference (P = 0.63). Four eyes
      with proliferative diabetic retinopathy in group TA(+) and five eyes with
      proliferative diabetic retinopathy in group TA(-) needed an additional filtering
      surgery. Group TA(+) (five eyes) had a lower incidence (P = 0.041) of reoperation
      caused by preretinal fibrous membrane formation than group TA(-) (13 eyes). No
      apparent corneal disorder or infectious signs were found in any eyes.
      CONCLUSIONS: Triamcinolone acetonide-assisted PPV appears to be potentially
      useful to reduce the incidence of reoperation owing to preretinal fibrosis with
      no serious complications.

PMID- 14707825
TI  - Triamcinolone-assisted pars plana vitrectomy for proliferative vitreoretinopathy.
AB  - PURPOSE: To determine whether triamcinolone acetonide (TAAC) staining facilitates
      posterior hyaloid and epiretinal membrane (ERM) removal in patients undergoing
      pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) with
      proliferative vitreoretinopathy (PVR). METHODS: Ten consecutive pseudophakic
      patients (10 eyes) underwent PPV for RRD with PVR. After a core PPV, a few drops
      of a commercially available TAAC aqueous suspension (40 mg/mL) with vehicle were
      injected into the mid vitreous cavity to visualize the posterior hyaloid, thus
      allowing a complete posterior hyaloidectomy. Next, 0.1 to 0.2 mL of TAAC was
      applied on the retinal surface to visualize and peel the ERMs. The tamponading
      agent was silicone oil (1,300 cs) in eight eyes and perfluropropane (C3F8 14%) in
      two eyes. The minimal follow-up period in all patients was 4 months. RESULTS: In
      all patients, intraoperative staining with TAAC consistently improved direct
      visualization and delineation of the posterior hyaloid and ERMs and facilitated
      their removal. No adverse reaction related to the use of TAAC was observed
      immediately postoperatively or 4 months after surgery. CONCLUSIONS: Intravitreal
      TAAC may be an important adjuvant tool in the delineation of posterior hyaloid
      and ERMs, allowing for a more complete and safer ERM removal in the surgical
      management of PVR complicating RRD. It is well tolerated with all its vehicle if
      used at low concentration and rapidly removed during surgery.

PMID- 14707826
TI  - Isolating triamcinolone acetonide particles for intravitreal use with a porous
      membrane filter.
AB  - PURPOSE: To report a new, simple, rapid method to isolate triamcinolone acetonide
      particles and to remove additives from its commercially available suspension
      (Kenacort-A) for intravitreal use. METHODS: The contents of a Kenacort-A vial (40
      mg triamcinolone acetonide suspended in 1.0 mL vehicle) were loaded into a
      syringe and passed through a porous membrane filter with 0.45-microm pores. The
      filter was then backflushed with distilled water to yield a vehicle-poor
      suspension of triamcinolone acetonide in the initial syringe. This filtration and
      backflush procedure was repeated four times, and each waste filtrate was
      subjected to high-performance liquid chromatography to identify benzyl alcohol, a
      preservative in the vehicle. Gel permeation chromatography was also used to
      determine the degree to which carboxymethylcellulose, one of the two suspending
      agents in the vehicle, permeated the membrane filter. Although 7.5 mg/mL high
      viscosity carboxymethylcellulose hardly passed through the 0.45-microm pore
      filter, it passed through the 5.0-microm pore filter easily. Therefore, a 5.0
      microm pore filter was used in this study. RESULTS: By using a 0.45-microm porous
      membrane filter, 99.7% of the benzyl alcohol can be eliminated. By using a 5.0
      microm porous membrane filter, but not by using a 0.45-microm porous membrane
      filter, 88.1% of the high-viscosity carboxymethylcellulose can be eliminated.
      CONCLUSIONS: The filtration and backflush procedure using the 5.0-microm porous
      membrane filters is useful during vitrectomy to reduce the preparation time of
      triamcinolone acetonide suspension. Also, this method of reducing additives may
      be more helpful when using triamcinolone as a therapeutic agent for intravitreal
      depot use, because there is no washout effect when it is used in this manner.

PMID- 14707827
TI  - Intravitreal tissue plasminogen activator in the management of central retinal
      vein occlusion.
AB  - PURPOSE: To evaluate the role of intravitreal tissue plasminogen activator (tPA)
      in the management of central retinal vein occlusion (CRVO) in patients with
      symptoms for <3 days. METHODS: We evaluated the visual outcome of a consecutive
      series of patients with CRVO following intravitreal tPA injection. All patients
      presented with visual acuity worse than 20/50 within 3 days from the onset of
      symptoms. Main outcome measures included percentage of patients whose final
      vision improved to 20/50 or better and change in percentage of patients with
      vision of 20/200 or worse before and after treatment. RESULTS: Twelve patients
      received intravitreal tPA for CRVO. Nine patients (75%) had best-corrected visual
      acuity of 20/200 or worse at presentation compared with 4 patients (33%) at the
      last follow-up after treatment. Five (55%) of these 9 patients had final visual
      acuity that improved to 20/50 or better. The remaining four patients did not have
      improvement or their vision continued to worsen. All 4 patients had fluorescein
      angiographic evidence of >10 disk areas of capillary nonperfusion at
      presentation. Overall, 8 (67%) of 12 patients had final visual acuity of 20/50 or
      better. No side effects related to tPA injection were observed. CONCLUSION: Our
      data suggest that intravitreal tPA injection may have a beneficial role in the
      management of CRVO when used within a few days of the onset of symptoms in
      patients with no angiographic evidence of severe capillary nonperfusion even if
      initial visual acuity is 20/200 or worse.

PMID- 14707828
TI  - Bilateral serous retinal detachments following organ transplantation.
AB  - PURPOSE: The authors report the physiopathogenetic features of bilateral serous
      neurosensory retinal detachments occurring in patients who have undergone organ
      transplantation. METHODS: The clinical and photographic findings of four patients
      who have undergone renal (3 cases) and liver (1 case) transplantation in whom
      bilateral serous retinal detachment developed early after surgery were reviewed.
      The patients were processed for clinical symptoms, visual acuity evaluation,
      slitlamp and fundus examinations, tonometry and fluorescein angiography. RESULTS:
      Ocular examination, in patients complaining of blurred vision and metamorphopsia,
      revealed loss of visual acuity, bullous serous neurosensory retinal detachment
      with retinal pigment epithelial detachments in fundus examination and areas of
      dye leakage in fluorescein angiography, despite tonometry and slitlamp
      examination were unremarkable. These alterations were spontaneously resolved with
      the normalization of renal function. CONCLUSION: The only common factor in each
      of the four patients resulted in alterations of the kidney function. This finding
      provides further evidence that renal failure may cause alterations in
      electrolytes extracellular distribution, leading to the formation of serous
      neurosensory retinal detachments.

PMID- 14707829
TI  - Lens-sparing vitreous surgery for infantile amblyogenic vitreous hemorrhage.
AB  - PURPOSE: To report on a series of infants with amblyogenic vitreous and/or
      subinternal limiting membrane hemorrhage managed by lens-sparing vitrectomy.
      DESIGN: Retrospective case series studying retinal attachment status and visual
      acuity. RESULTS: Eleven eyes sustained vitreous hemorrhage as a consequence of
      shaken baby syndrome, 1 due to hyaloidal canal hemorrhage extending into the
      vitreous, 1 due to Terson syndrome, 1 due to birth trauma, and 2 due to a
      presumed coagulation disorder. Age of the patients at the time of surgery ranged
      from 2 to 23 months (age adjusted for prematurity). Follow-up ranged from 7 to 81
      months (mean, 28 months). Ten eyes had visual improvement. Two infants with
      shaken baby syndrome had bilateral nonrecordable flash visual evoked potential
      before surgery; one eye of one infant had a better than expected visual outcome
      after surgery. One eye sustained a retinal tear without detachment. One eye in an
      infant with severe shaken baby syndrome and traumatic retinopathy developed a
      total rhegmatogenous retinal detachment with proliferative vitreoretinopathy.
      CONCLUSIONS: Infantile amblyogenic vitreous hemorrhage may be effectively managed
      by lens-sparing vitreous surgery. Visual outcome of shaken baby syndrome may be
      limited as a consequence of structural damage to the retina, optic nerve, or
      posterior visual pathways.

PMID- 14707830
TI  - Subretinal fluid analysis in the diagnosis of choroidal tuberculosis.
AB  - BACKGROUND: Diagnosis of intraocular tuberculosis is often difficult. A choroidal
      granulomalike lesion suspected to be the result of tuberculosis could be of other
      inflammatory, infective, or neoplastic causes. We report two cases in which a
      choroidal granuloma with exudative retinal detachment was diagnosed as
      tuberculosis by the detection of acid-fast bacilli in subretinal fluid. METHODS:
      Interventional case series. RESULTS: Two female patients had choroidal granulomas
      with surrounding exudative retinal detachment. Detailed laboratory investigations
      were unhelpful in diagnosis, and the patients' conditions worsened with systemic
      steroid therapy. Subretinal fluid was tapped and revealed acid-fast bacilli and
      grew Mycobacterium tuberculosis on culture. CONCLUSION: Subretinal fluid analysis
      can help in the detection of tuberculous granuloma and facilitate successful
      management.

PMID- 14707831
TI  - The role of lanreotide in the treatment of choroidal neovascularization secondary
      to age-related macular degeneration: a pilot clinical trial.
AB  - PURPOSE: To evaluate the role of somatostatin in the treatment of subfoveal
      choroidal neovascularization (CNV). METHODS: Twenty eyes of 20 patients with CNV
      were included in the study. Patients were randomly allocated to treatment with
      lanreotide (10 eyes) or placebo (10 eyes). Patients received one intramuscular
      injection of lanreotide or placebo every 15 days for a total of 6 months. Follow
      up lasted for 6 months for the control group and 12 months for the study group.
      The changes in visual acuity and fluorescein angiography at 6 months were
      compared between the two groups. In addition, the changes in the same parameters
      within the study group, from 6 to 12 months, were studied. RESULTS: From baseline
      to 6 months, the mean visual acuity and surface area of hyperfluorescence
      remained stable in the study group, while the intensity of hyperfluorescence
      decreased. After discontinuation of treatment, deterioration of all three
      parameters was noted in the study group. Statistical analysis, however, failed to
      reveal any significant difference from baseline. CONCLUSIONS: During treatment
      with lanreotide, a trend for stabilization of visual acuity and intensity of
      hyperfluorescence was documented in the study group, but it did not reach
      statistically significant levels. Further randomized, controlled clinical trials
      with larger samples and longer duration of treatment and follow-up are warranted
      to evaluate the role of lanreotide in the treatment of age-related CNV.

PMID- 14707832
TI  - Squalamine lactate reduces choroidal neovascularization in a laser-injury model
      in the rat.
AB  - PURPOSE: To determine if systemically administered squalamine lactate, a novel
      aminosterol with antineoplastic and antiangiogenic activity, inhibits the
      development of experimental choroidal neovascularization membranes (CNVMs)
      induced by laser trauma in a rat model. METHODS: Twenty anesthetized male Brown
      Norway rats received a series of 8 krypton red laser lesions per eye (647 nm,
      0.05 second, 50 microm, 150 mW). One half the animals received an intraperitoneal
      injection of squalamine and the other one half received an injection of 5%
      dextrose in water, all performed in a masked fashion. Fundus photography and
      fluorescein angiography were performed at postlaser treatment days 14 and 28, and
      ocular tissues were processed for light microscopic examination following
      euthanasia of the rats on postlaser treatment day 28. RESULTS: Although fundus
      photography and fluorescein angiography yielded no statistically significant
      quantitative differences between the two groups, histologic analysis of the
      lesion sites revealed a partial but statistically significant reduction of
      experimental CNVM development in the squalamine-treated population. In
      particular, the squalamine-treated eyes (n = 20) demonstrated lesions (n = 149)
      with a mean CNVM thickness +/- SD of 47 +/- 11 microm, as compared with the
      control eyes (n = 20) that had lesions (n = 142) with a mean CNVM thickness +/-
      SD of 63 +/- 14 microm (P < 0.001). CONCLUSION: Systemically administered
      squalamine lactate partially reduced choroidal neovascular membrane development
      induced by laser trauma in this animal model. In conjunction with other existing
      and developing therapies, this agent may have a potential role in the treatment
      of human CNVM formation. Further study of squalamine lactate for treatment of
      neovascular eye disease is warranted.

PMID- 14707833
TI  - Evaluation and comparison of lens and peripheral retinal relationships with the
      use of endolaser probe and newly designed curved vitrectomy probe.
AB  - OBJECTIVE: To evaluate and compare the relationships between the posterior
      surface of the crystalline lens and peripheral retina with the use of curved
      vitrectomy instruments. MATERIALS AND METHODS: Specially designed curved
      endolaser and vitrectomy probes were compared with conventional straight probes
      through sclerotomy sites at 3.0 mm and 4.0 mm, in 12 fresh cadaver phakic eyes.
      For the safety profile, the perpendicular distance between the probe oriented
      toward a reference point on the retina and the midpoint of the posterior surface
      of the lens was measured. For access to the retinal periphery, the distance
      between the ora serrata and the most peripheral accessible point on the retina
      without touching the crystalline lens with the probes was measured. RESULTS: The
      perpendicular distance between the probe and posterior surface of the lens
      increased, and the ability of the probe to reach the most peripheral accessible
      point on the retina improved with the curved probes as compared with straight
      probes. CONCLUSIONS: Curved probes can access the peripheral retina and ora
      serrata with lesser possibility to injure the crystalline lens during vitreous
      surgery than the standard straight probes.

PMID- 14707834
TI  - Serous detachment of the retina.

PMID- 14707835
TI  - Diagnostic and therapeutic challenges.

PMID- 14707836
TI  - Diagnostic and therapeutic challenges.

PMID- 14707837
TI  - Development of a large macular fold following surgical repair of a traction
      retinal detachment in a child with x-linked retinoschisis.

PMID- 14707838
TI  - A new 668-NM diode laser for retinochoroidal photocoagulation therapy.

PMID- 14707839
TI  - Management of the posterior segment foreign bodies with a simple snare.

PMID- 14707840
TI  - A modified technique for the management of completely dislocated posterior
      chamber intraocular lenses in the absence of capsular support.

PMID- 14707841
TI  - Optical coherence tomography findings in photic maculopathy.

PMID- 14707842
TI  - Presumed malignant plasmacytoma of the choroid as the first manifestation of
      multiple myeloma.

PMID- 14707843
TI  - Recovery of visual function after removal of chronic subfoveal perfluorocarbon
      liquid.

PMID- 14707844
TI  - Foveal shape after idiopathic macular hole surgery with and without internal
      limiting membrane removal.

PMID- 14707845
TI  - Subluxated/dislocated lens and hyphema as features of retinoblastoma.

PMID- 14707846
TI  - Choroidal metastasis from adenocarcinoma of the esophagus.

PMID- 14707847
TI  - Rapidly developing cotton-wool spots as the first manifestation of systemic non
      Hodgkin's lymphoma.

PMID- 14707848
TI  - Epiretinal membrane occurring with myelinated retinal nerve fibers and vascular
      abnormalities.

PMID- 14707849
TI  - Introduction of a new method for the preparation of triamcinolone acetonide
      solution as an aid to visualization of the vitreous and the posterior hyaloid
      during pars plana vitrectomy.

PMID- 14707850
TI  - Triamcinolone acetonide-assisted peeling of retinal internal limiting membrane
      for macular surgery.

PMID- 14707851
TI  - Delamination of the retinal internal limiting membrane using blunt dissection and
      indocyanine green staining.

PMID- 14707852
TI  - Crystalline retinopathy associated with retinal dialysis and chronic retinal
      detachment.

PMID- 14707853
TI  - Method of macular hole repair with minimal vitrectomy.

PMID- 14707854
TI  - Does radial optic neurotomy induce surgical optociliary vessels in central
      retinal vein occlusion?

PMID- 14707855
TI  - Results of retinal detachment surgery in Marfan syndrome in Asians.

PMID- 14707856
TI  - Radial optic neurotomy as a treatment of central vein occlusion: neurotomy in
      central vein occlusion.

PMID- 14707858
TI  - Steam-sterilize Volk clariVit lenses.

PMID- 14707857
TI  - Inexpensive illuminated vitrectomy cutter.

PMID- 14707859
TI  - Twin lights: a new chandelier illumination for bimanual surgery.

PMID- 14707860
TI  - Most osteomalacia-associated mesenchymal tumors are a single histopathologic
      entity: an analysis of 32 cases and a comprehensive review of the literature.
AB  - Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due
      to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue
      variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently
      associated with OO. Despite its association with OO, many PMTMCTs go unrecognized
      because they are erroneously diagnosed as other mesenchymal tumors. Expression of
      fibroblast growth factor-23 (FGF-23), a recently described protein putatively
      implicated in renal tubular phosphate loss, has been shown in a small number of
      mesenchymal tumors with known OO. The clinicopathological features of 32
      mesenchymal tumors either with known OO (29) or with features suggestive of
      PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin,
      desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged
      from 9 to 80 years in age (median 53 years). A long history of OO was common. The
      cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3),
      osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a
      variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm.
      Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland
      spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels,
      microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous
      ossification. Four of these benign-appearing PMTMCTs contained osteoid-like
      matrix. Three other PMTMCTs were hypercellular and cytologically atypical and
      were considered malignant. The 3 cases without known OO were histologically
      identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal
      HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed
      actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21
      cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases,
      6-348 months) indicated the following: 21 alive with no evidence of disease and
      with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung
      metastases). We conclude that most cases of mesenchymal tumor-associated OO, both
      in the present series and in the reported literature, are due to PMTMCT. Improved
      recognition of their histologic spectrum, including the presence of bone or
      osteoid-like matrix in otherwise typical cases and the existence of malignant
      forms, should allow distinction from other mesenchymal tumors. Recognition of
      PMTMCT is critical, as complete resection cures intractable OO.
      Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in
      PMTMCT-associated OO.

PMID- 14707861
TI  - Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic
      potential indistinguishable from animal-type melanoma and epithelioid blue nevus.
AB  - In the course of a study of borderline melanocytic tumors, we observed a
      distinctive group of lesions characterized by features very similar to those
      previously described in the literature as "animal-type melanoma" and epithelioid
      blue nevus of Carney complex. We have designated these lesions as pigmented
      epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis
      of 41 consecutive PEM from 40 patients and compare them with 11 epithelioid blue
      nevi from patients with Carney complex. PEM occurred in both sexes of different
      ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The
      median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide
      distribution with extremities being the most common site. The tumors were formed
      by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily
      pigmented epithelioid and/or spindled melanocytes. Five lesions were part of
      combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in
      1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph
      nodes contained metastases (46%). Liver metastases occurred in 1 case. None of
      the patients died of disease. Clinical follow-up of more than a year (mean 32
      months, range up to 67 months) was available in 27 cases (67%). We found no
      histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration
      was the only feature more common in PEM than epithelioid blue nevi of Carney
      complex. Otherwise, they were histologically indistinguishable. Our data show
      that PEM is a unique low-grade variant of melanoma with frequent lymph node
      metastases but indolent clinical course. We suggest that PEM be considered as a
      provisional histologic entity encompassing both animal-type melanoma and
      epithelioid blue nevus.

PMID- 14707862
TI  - Oral plasmablastic lymphomas in AIDS patients are associated with human
      herpesvirus 8.
AB  - Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi
      sarcoma, primary effusion lymphoma (PEL), and Castleman's disease. To our
      knowledge, infection by this virus has not been strongly associated with other
      hematopathologic malignancies. We examined five oral cavity lymphomas from men
      with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain
      reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ
      hybridization and HHV8 protein with immunohistochemistry. Four of these tumors
      were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma.
      Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and
      protein. Further, the four plasmablastic lymphoma cases had tumor cells that
      contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in
      surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of
      the five oral cavity lymphomas from people who did not have acquired
      immunosuppression nor in five lymphomas from AIDS patients that were located at a
      site other than the oral cavity. It is concluded that oral cavity lymphomas from
      people with AIDS are strongly associated with infection by HHV8 and EBV. Given
      the poor prognosis of oral cavity lymphomas in immunocompromised patients,
      therapy directed against the HHV8 and EBV infection may be of therapeutic value.

PMID- 14707863
TI  - Radiation-induced histopathologic changes of the breast: the effects of time.
AB  - The increasingly frequent use of radiation therapy (RT) and systemic chemotherapy
      (CT) in the treatment of breast carcinoma requires surgical pathologists and
      cytologists to be familiar with the variable histologic changes initiated by
      these agents. Both treatment modalities can cause severe epithelial
      abnormalities, which are difficult to distinguish from carcinoma. The progression
      or regression of these histologic abnormalities in nonneoplastic breast tissue
      have not been extensively evaluated. Our study used 120 post-RT biopsy or
      mastectomy specimens from 117 patients (3 had bilateral carcinoma treated with
      RT) yielding 120 specimens. The interval from post-RT to biopsy or mastectomy
      ranged from 1 to 229 months with 25 of the specimens obtained 1 to 12 months
      after cessation of RT and 95 more than a year post-RT. Twenty-seven specimens
      were from >6 years after RT. The histologic features of pretreatment and
      posttreatment specimens were graded (0-3) blindly for each histologic feature to
      include stromal vascular and fibroblastic changes and epithelial cell changes of
      the terminal duct lobular unit and extralobular ducts as well as terminal duct
      lobular unit fibrosis/atrophy. The changes between the pre- and post-RT grades
      were all statistically significant (P < 0.05) using multiple nonparametric
      statistical methods and the parametric Student t test. The specimens obtained
      within the first year post-RT were compared with those from >1 year post-RT, >3
      years post-RT, and >6 years post-RT. None of the histologic features evaluated
      showed significant changes over the various time intervals regardless of the
      statistical method used. The absence of regression of the radiation-induced
      histologic changes over time mandates the surgical pathologist be alert to the
      possibility of RT or CT even without that therapeutic history.

PMID- 14707864
TI  - CD10 expression in extranodal dissemination of angioimmunoblastic T-cell
      lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a systemic disease that often has
      evidence of extranodal involvement at presentation. In a recent study of lymph
      nodes in AITL, we showed that the neoplastic T cells in most cases can be
      identified by aberrant expression of CD10. The aim of this study was to
      investigate whether CD10 expression by the neoplastic T cells is maintained in
      extranodal sites. Ten cases of AITL with histologic and immunophenotypic evidence
      of extranodal dissemination were studied. Seven cases of peripheral T-cell
      lymphoma unspecified (PTLu), that included biopsies of involved extranodal sites,
      two cases of enteropathy type T-cell lymphoma (ETTL), and one case of extranodal
      NK/T lymphoma, nasal type were selected as controls. Diagnostic lymph node
      biopsies and biopsies of extranodal sites were reviewed. PCR for T-cell clonality
      and single layer immunostaining for CD3, CD20, CD10, and CD21 and double layer
      immunostaining for CD20/CD10 were performed. All 10 cases of AITL had
      characteristic histologic features and molecular evidence of the disease in lymph
      node biopsies. In these cases, aberrant CD10 expression was maintained in the
      lung, cecum, tonsil, nasopharynx, and one of six involved bone marrow trephines.
      In these extranodal biopsies, the distribution of CD10-positive tumor cells
      correlated with that of the follicular dendritic cell meshwork (FDC). The five
      bone marrow trephines that lacked aberrant CD10 expression were devoid of
      morphologic and immunohistochemical evidence of FDC. In these five cases, there
      was evidence of aberrant CD10 expression in other involved sites that had FDC.
      The neoplastic cells in PTLu, ETTL, and extranodal NK/T lymphoma, nasal type were
      CD10 negative. Our data show that aberrant CD10 expression is a useful phenotypic
      marker for diagnosis of AITL in most involved extranodal sites, except bone
      marrow, and suggest a possible role of FDC in the pathogenesis of AITL.

PMID- 14707865
TI  - Airway-centered interstitial fibrosis: a distinct form of aggressive diffuse lung
      disease.
AB  - We describe 12 patients with a form of interstitial lung disease characterized
      pathologically by small airway-centered interstitial fibrosis and metaplastic
      bronchiolar epithelium extending around and often linking fibrotic and sometimes
      heavily muscularized bronchioles. Clinically, patients presented with chronic
      cough and progressive dyspnea. One was a current light smoker and two were ex
      smokers. In 8 patients, a history of possible inhalational exposures, including
      wood smoke, birds, cotton, pasture, chalk dust, agrochemical compounds, and
      cocaine use, was elicited. Pulmonary function tests showed moderate to severe
      physiologic abnormalities, in most instances indicating a restrictive lung
      disease with decreased peripheral flow rates. Chest radiographs revealed
      predominantly diffuse reticulonodular infiltrates in the central lung fields,
      with thickening of the bronchial walls and decreased lung volumes. Chest computed
      tomography demonstrated peribronchovascular fibrosis and interstitial thickening.
      Bronchoalveolar lavage showed a mild increase in lymphocytes in 4 subjects.
      Patients were treated with corticosteroids and bronchodilators. Follow-up data
      were available in 10 patients. In 5 patients, the disease progressed and 4 of
      them died. Two patients remained stable and 3 improved or healed. We propose that
      these findings represent a distinct airway-centered disease that mostly behaves
      as an interstitial lung disease and may exhibit a poor outcome.

PMID- 14707866
TI  - Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma.
AB  - Alpha-methylacyl-CoA racemase (AMACR) was first discovered by using cDNA
      microarray technology as a molecular marker for prostate cancer. Our recent
      microarray analysis of renal cell carcinomas showed a significant increase of
      AMACR mRNA levels in papillary renal cell carcinomas, but not in other subtypes.
      To investigate the value of this marker in pathologic diagnosis, we analyzed
      AMACR mRNA levels in cDNA microarrays from 70 kidney tumors. Furthermore, we
      evaluated the AMACR expression in 165 kidney tumors on tissue microarrays and 51
      papillary carcinomas of other organs by immunohistochemistry. AMACR mRNA was
      significantly overexpressed in 7 of 8 papillary renal cell carcinomas with an
      average of 5.2-fold increase, and only in 2 of 62 nonpapillary kidney tumors.
      Immunohistochemistry demonstrated strong AMACR positivity in all cases of
      papillary renal cell carcinomas (41 of 41, 100%), including 6 metastatic
      papillary renal cell carcinomas, but only focal or weak reactivity in the
      minority (18 of 124, 15%) of other renal tumors including 13 of 52 clear cell
      renal cell carcinomas, 3 of 20 oncocytomas, and 2 of 17 urothelial carcinomas.
      All chromophobe (0 of 18) and sarcomatoid components of renal cell carcinomas (0
      of 15) were negative for AMACR. Weak or focal AMACR immunoreactivity was detected
      in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14
      thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of
      6 pancreas). Using a combination of cDNA microarrays, tissue microarrays, and
      immunohistochemistry, we identified AMACR as a marker for papillary renal cell
      carcinoma, which could be valuable in subclassification of renal cell carcinomas
      and in the differential diagnosis of a metastatic papillary carcinoma.

PMID- 14707867
TI  - Infarcted adenomatoid tumor: a report of five cases of a facet of a benign
      neoplasm that may cause diagnostic difficulty.
AB  - We describe five cases in which adenomatoid tumors showed extensive necrosis,
      presumably due to infarction, and posed diagnostic difficulty. The tumors
      occurred in four males (three with epididymal tumors and one with an
      intratesticular tumor) and one female (with a parafallopian tube tumor) 35 to 44
      years of age. Two of the men presented with acute scrotal pain simulating
      epididymitis, and two with a palpable mass. The parafallopian tube tumor was an
      incidental finding. The tumors were solitary, grossly well-circumscribed,
      uniformly solid masses that ranged in size from 1.1 to 3.5 cm. Microscopically,
      they were all characterized by central necrosis with pale mummified adenomatoid
      tumor identified at least focally but often overshadowed by nondescript necrotic
      tissue. Viable adenomatoid tumor was identified in all cases but was minor in
      amount in two of them. The necrosis was surrounded by a florid reactive process
      of fibroblasts and myofibroblasts that had plump nuclei often with prominent
      nucleoli, and occasional mitoses. Two of the epididymal cases had adjacent rete
      testis showing epithelial hyperplasia with hyaline globule formation. The
      microscopic appearance often suggested the possibility of a malignant neoplasm
      because of: 1) blurring of the normal relatively easily identifiable junction
      between adenomatoid tumor and adjacent tissue; 2) irregular pseudo-infiltration
      of fat by reactive tissue and adenomatoid tumor; 3) paucity of typical
      adenomatoid tumor due to the infarction and the fact that viable tumor usually
      showed a solid pattern; and 4) atypia of the associated reactive cells. This
      unemphasized feature of adenomatoid tumors may potentially lead to more
      aggressive therapy than warranted if it is not correctly interpreted.

PMID- 14707868
TI  - Angiotensin I-converting enzyme (CD143) is down-regulated in focal nodular
      hyperplasia of the liver.
AB  - In surgical pathology, focal nodular hyperplasia (FNH) is sometimes difficult to
      diagnose, and liver cirrhosis (LC) and hepatocellular adenoma (HA) are often
      among the differential diagnoses. Recently, we found a reduced expression of
      angiotensin I-converting enzyme (CD143) in FNH compared with cirrhotic and
      noncirrhotic liver. Intrigued by this observation, we investigated the expression
      pattern of CD143 in FNH, LC, and HA and its possible diagnostic value. The
      expression of CD143 was studied by immunohistochemistry in 20 FNHs, 13
      corresponding extralesional noncirrhotic liver parenchyma, 20 patients with LC,
      and four HAs. Endothelial cells were identified with antibodies directed against
      CD31 and CD34. CD31+, CD34+, and CD143+ sinusoidal endothelial cells were found
      in extralesional liver, LC, HA, and FNH. However, the number of CD143+ sinusoidal
      endothelial cells and the intensity of immunostaining were significantly reduced
      in FNH compared with extralesional liver, LC, and HA. The expression of CD143 was
      further assessed using a numerical scoring system ranging from 0 to 6. The mean
      immunoreactivity score for CD143 was 2.4 +/- 1.7 for sinusoidal endothelial cells
      in FNH, 5.7 +/- 0.6 in extralesional liver, 4.8 +/- 1.1 in LC, and 5.8 +/- 0.5 in
      HA. The differences between the mean immunoreactivity scores for CD143 were
      highly significant. The difference between FNH and extralesional liver was
      confirmed on transcriptional level by fluorescence-mediated real-time RT-PCR,
      which also showed a significantly decreased level of CD143 mRNA in FNH. Our study
      provides evidence that CD143 is down-regulated in FNHs and that the phenotype of
      endothelial cells lining the sinusoids in FNH differs from those in non
      neoplastic liver, LC, and HA. The observed variations in expression patterns for
      CD143 might be of diagnostic use in surgical pathology.

PMID- 14707869
TI  - Signet-ring cell (mucin-producing) adenocarcinomas of minor salivary glands.
AB  - We report seven cases of minor salivary gland carcinomas characterized by the
      marked presence of mucin-containing signet-ring cells. These tumors were
      distinctive in their microscopic appearance and displayed features not seen in
      any other type of salivary gland malignancy. They typically exhibited invasive
      growth by narrow parallel strands, randomly scattered small nests, or
      individually infiltrating cells. Solid, cribriform, or targetoid areas were
      absent, as well as papillary components. Ductal differentiation was minimal, and
      seen in only four cases. Degrees of cellularity varied from one area to another.
      The tumors were cytologically bland. We think that these tumors represent a
      unique subset of intraoral minor salivary gland carcinomas.

PMID- 14707870
TI  - Paraganglioma of the urinary bladder: a lesion that may be misdiagnosed as
      urothelial carcinoma in transurethral resection specimens.
AB  - Paraganglioma of the urinary bladder is a rare tumor with characteristic
      histologic and immunohistochemical features. However, in our experience, it may
      be misdiagnosed as urothelial cancer because of 1) its frequent involvement of
      the muscularis propria; 2) morphology that may suggest urothelial cancer in
      transurethral resection specimens, particularly if there are artifactual changes
      induced by that procedure; 3) failure of pathologists to include it in their
      differential diagnosis when evaluating a bladder tumor; and 4) only a minority of
      the cases are associated with symptoms that might prompt consideration of the
      diagnosis. Distinction between paraganglioma and urothelial cancer is important
      because of likely different therapeutic options. In this report, we describe our
      experience with the histopathology of paragangliomas of the urinary bladder with
      emphasis on the histologic features that have led to their being misdiagnosed as
      conventional urothelial cancer and, most importantly, those that will help
      pathologists recognize this rare tumor of the bladder. Fifteen cases of
      paraganglioma of the urinary bladder were studied, 11 of them consult cases. They
      affected patients (8 male, 7 female) with a mean age of 49.5 years; only two had
      symptoms suggestive of the diagnosis, including hypertension during cystoscopy
      and episodic headache. Three consult cases were submitted with a diagnosis of
      "transitional cell carcinoma" and 4 with a diagnosis only of "bladder tumor."
      Histologically, "zellballen" and diffuse patterns were present in 12 (80%) and 3
      (20%) of the cases. A delicate fibrovascular stroma was obvious in 14 (93%)
      cases. Other patterns included irregular nests and pseudorosette formation. Tumor
      necrosis, significant cautery artifact, and muscularis propria invasion were
      present in 1 (7%), 3 (20%) cases, and 10 (67%) cases, respectively. All 15 tumors
      were composed of large polygonal cells with abundant granular cytoplasm. Focal
      clear cells were present in 3 (20%). The nuclei were mostly uniform, although
      occasional pleomorphic nuclei were seen in 6 (40%) cases, and 2 (13%) had
      frequent pleomorphic nuclei. Mitoses were rare overall, and no abnormal mitotic
      figures were found. The major histologic features that led to misdiagnosis
      included a diffuse growth pattern, focal clear cells, necrosis, and muscularis
      propria invasion, with significant cautery artifact compounding the diagnostic
      problems. Immunohistochemically, 2 of 2 tumors were positive for neuron-specific
      enolase, 9 of 10 tumors for chromogranin, and 2 of 3 tumors for synaptophysin; 3
      of 3 tumors were negative for cytokeratin and 1 of 1 tumor negative for HMB-45.
      Paraganglioma of the urinary bladder may be misdiagnosed as urothelial cancer,
      but a careful search for the characteristic histologic features and, if
      necessary, supportive immunohistochemical studies, should lead to a correct
      diagnosis.

PMID- 14707871
TI  - Molecular genotyping of medullary thyroid carcinoma can predict tumor recurrence.
AB  - Medullary thyroid carcinoma can have an aggressive behavior, and little is known
      about the molecular basis for clinical outcome. Defining risk of recurrent or
      metastatic disease is difficult, and it has been limited to clinical and
      pathologic features, such as advanced age, cervical lymph node metastases, and
      stage at presentation. Using microdissection and genotyping, we studied 11 cases
      of medullary carcinoma for allelic losses in a panel of known tumor suppressor
      genes. The tumor suppressor genes with the most frequent allelic losses were NF2,
      l-myc, and p53 (75%, 44%, and 44%, respectively). The average frequency of
      allelic loss across all tumors was 44% and was higher in tumors that recurred. A
      combination of previously described high-risk variables (increased patient age
      and cervical lymph node metastases) with the frequency of allelic loss yielded a
      high-risk group, in which 6 of 6 patients recurred, and a low-risk group, in
      which 0 of 5 patients recurred (P = 0.004). Frequency of allelic loss in tumor
      suppressor genes may provide a useful adjunctive prognostic test in medullary
      thyroid carcinoma.

PMID- 14707872
TI  - Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a
      dendritic cell origin.
AB  - Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the
      gastrointestinal tract that consist of spindle-shaped stromal cells and an
      inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis
      remain unknown. Based on previous reports of their immunoreactivity for CD34 and
      c-kit biomarkers, IFPs have been thought to be related to gastrointestinal
      stromal tumors (GISTs). After reviewing the current literature and examining IFPs
      at the light microscopic level, we evaluated a series of IFPs using an extensive
      panel of immunohistochemical and in situ hybridization markers in an effort to
      gain insight into their etiology and histogenesis and to determine their true
      relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1
      ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34,
      HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma
      kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell
      factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8
      (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also
      performed. Ten cases were further evaluated for the dendritic cell markers
      fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and
      fascin in all (100%) cases, and these stromal cells were, in addition,
      immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases,
      respectively. CD35 was also found to be focally reactive in the stromal cells.
      Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical
      markers and EBER were negative in the stromal cells. These findings suggest that
      the proliferating stromal cells in IFPs are of dendritic cell origin, with some
      cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h
      caldesmon immunoreactivity fails to support a relationship to GISTs. We also
      conclude that Epstein Barr virus and HHV8 are unlikely etiologic agents of IFPs.
      Overexpression of cyclin D1 in all cases suggests that a defect in cell-cycle
      regulation may be involved in the growth of IFPs.

PMID- 14707873
TI  - Leiomyosarcoma of the penis: a clinicopathologic study of 14 cases with review of
      the literature and discussion of the differential diagnosis.
AB  - Primary leiomyosarcomas of the penis are very rare. To date, less than 30 have
      been documented in the English language literature. In this report, we describe
      the clinical, histopathologic, and immunohistochemical findings in 14 cases
      retrieved from our files. The patients ranged in age from 43 to 62 years (mean
      age, 51 years) at the time of initial surgical resection. The tumors involved the
      prepuce (n = 1), prepuce and distal shaft (n = 1), circumcision scar line (n =
      2), circumcision scar line and distal shaft (n = 1), shaft (n = 5), base of the
      penis (n = 3), and penis, not otherwise specified (n = 1). The lesions ranged in
      size from 0.5 to 6.0 cm (median size, 1.5 cm) in greatest dimension. Nine tumors
      were superficially located, two were of indeterminate depth, and three were deep
      seated. The superficial tumors were relatively asymptomatic, and seven were
      reportedly present for 1 year to more than 20 years (median duration, 5 years)
      before medical attention was sought. In contrast, one deep-seated lesion caused
      dysuria and difficulty voiding, prompting the patient to seek a clinical opinion
      within only a few months of the apparent onset. Histologically, all tumors
      contained smooth muscle cells with both cytologic atypia and mitotic activity.
      Immunohistochemical studies were available for nine tumors, and immunoreactivity
      for desmin was present in all instances. All patients were initially treated with
      a local procedure. Follow-up information is available for 9 of the 14 patients
      (64%), with a median follow-up interval of 12 years 11 months. Three patients had
      multiple (two to four) local recurrences. Two of these patients were ultimately
      treated with a wide local excision or partial penectomy, and both were alive and
      well at last follow-up. In contrast, one patient, who had four local recurrences
      and refused a penectomy, developed a distant metastasis 10 months after the
      fourth recurrence. The best predictors of outcome are tumor depth and tumor size.
      Superficial leiomyosarcomas of the penis are optimally managed by wide local
      excision whenever this is technically feasible. Tumors with a deep-seated
      component may require more aggressive intervention to ensure complete removal.

PMID- 14707874
TI  - Diagnostic agreement in the evaluation of image-guided breast core needle
      biopsies: results from a randomized clinical trial.
AB  - BACKGROUND: Image-guided core needle biopsies (CNBs) are commonly used as the
      initial sampling method for nonpalpable, mammographically detected breast
      lesions. Although prior studies have shown that this procedure is a highly
      sensitive and accurate method for the detection of breast cancer, the level of
      diagnostic agreement between pathologists in the analysis of CNB has not been
      previously studied in detail. METHODS: To address this, we reviewed the
      pathologic findings in 2004 CNB from patients enrolled in the Radiologic
      Diagnostic Oncology Group 5 study, a randomized, multicenter trial designed to
      determine the role of CNB and fine needle aspiration biopsy in the evaluation of
      nonpalpable breast lesions. Slides of CNB specimens were initially diagnosed by
      pathologists at the 22 participating institutions (local diagnosis) and were then
      sent to the study pathologists for central review (central diagnosis). Local and
      central diagnoses were compared. RESULTS: Overall, the central diagnosis and
      local diagnosis were concordant in 1925 cases (96%), indicating an excellent
      level of agreement by kappa statistic analysis (kappa = 0.90; 95% confidence
      interval 0.88-0.92). The level of agreement between local and central
      pathologists did not vary with the image guidance system (stereotactic
      mammography vs. ultrasound) or with the mammographic findings (soft tissue
      density vs. microcalcifications). The level of diagnostic agreement observed for
      CNB was comparable to that observed among 596 open surgical biopsies obtained
      from patients in this study and subjected to central pathology review (93%
      agreement; kappa = 0.89, 95% confidence interval 0.86-0.92). CONCLUSIONS: The
      level of diagnostic agreement in interpretation of breast CNB is extremely high
      among pathologists and is comparable to that seen for open surgical biopsy.

PMID- 14707875
TI  - Cystic adenomatoid tumor of the mediastinum.
AB  - A case of adenomatoid tumor presenting as a mass in the anterior mediastinum is
      described. The patient was a 56-year-old woman with left side chest wall pain who
      showed a mediastinal mass on chest x-ray and CT scans. Thorough clinical and
      radiographic examination did not reveal any evidence of tumor elsewhere. At
      surgery, the tumor was found adjacent to the anterior pericardial reflection.
      Grossly, the tumor measured 5.5 x 5.5 x 3 cm and showed a homogeneous cut surface
      with numerous cystic structures that varied from 0.5 to 1.5 cm in greatest
      diameter. Histologic examination showed numerous cystic spaces lined by flattened
      or cuboidal epithelial cells. The walls of the cysts showed a proliferation of
      small canalicular structures lined by round to polygonal epithelioid cells with
      vacuolated eosinophilic cytoplasm. Immunohistochemical studies showed strong
      positivity of the epithelioid cells for AE1/AE3 cytokeratin, CK5/CK6, and
      calretinin. Stains for CK7, CK20, alpha-fetoprotein, CD31, carcinoembryonic
      antigen, MOC 31, and chromogranin were negative. Electron microscopic examination
      showed numerous long microvilli on the cell surface and abundant
      tonofilaments/desmosomal plaques in the tumor cells, characteristic of
      mesothelial cells. The patient is alive and well and free of recurrence 1 year
      following surgery. Adenomatoid tumor is a rare neoplasm that should be added in
      the differential diagnosis of anterior mediastinal masses. Immunohistochemical
      and ultrastructural studies may be of aid in identifying the characteristic
      features of mesothelial cells and to avoid mistaking this lesion for more ominous
      conditions.

PMID- 14707876
TI  - Solitary fibrous tumor of the cerebellopontine angle with salivary gland
      heterotopia: a unique presentation.
AB  - We report the unique association of a solitary fibrous tumor of the
      cerebellopontine angle with ectopic salivary gland tissue in a 53-year-old woman.
      The patient, diagnosed 21 years earlier with a right cerebellopontine angle
      fibrous meningioma, presented with a recurrent mass, which, upon surgical
      removal, showed features of a solitary fibrous tumor. Strong and diffuse
      immunoreactivity to CD34 and BCL-2 and a negative epithelial membrane antigen
      immunostain confirmed the diagnosis. Admixed with the spindle cell neoplasm, a
      bland glandular element composed of small glands and variably dilated tubules was
      noted. The vague tubuloacinar arrangement of the glands and the presence of
      acinar cells with a granular, periodic acid-Schiff-positive, basophilic
      cytoplasm, resembling serous type acini, were features of benign, although
      ectopic, salivary gland tissue. The presence of a myoepithelial cell layer,
      surrounding some of the acini and highlighted by the smooth muscle actin
      immunostain, strengthened this interpretation.

PMID- 14707877
TI  - Estimating nonfatal traumatic brain injury hospitalizations using an urban/rural
      index.
AB  - OBJECTIVE: To develop state-level estimates of the annual number of nonfatal
      cases of traumatic brain injury (TBI) resulting in hospitalization. METHODS: The
      estimation process incorporates annual nonfatal TBI hospitalization case counts
      from 15 states funded by the Centers for Disease Control and Prevention to
      conduct TBI surveillance; annual fatal TBI case counts based on National Center
      for Health Statistics data for all 50 states; and an index reflecting the
      urban/rural character of each state. These data are used to develop a negative
      binomial regression model that yields estimates of the annual number of nonfatal
      TBI hospitalization cases for each state not funded to conduct TBI surveillance.
      RESULTS: Sensitivity analysis suggests that on average the estimates fall within
      +/- 15% of the case counts that would be obtained directly from surveillance.
      CONCLUSION: In combination, the TBI case count data and the urban/rural index
      support effective modeling and estimation of annual nonfatal TBI hospitalization
      case counts at the state level.

PMID- 14707878
TI  - Further psychometric evaluation and revision of the Mayo-Portland Adaptability
      Inventory in a national sample.
AB  - OBJECTIVES: To evaluate the internal consistency of the Mayo-Portland
      Adaptability Inventory (MPAI), further refine the instrument, and provide
      reference data based on a large, geographically diverse sample of persons with
      acquired brain injury (ABI). SUBJECTS: 386 persons, most with moderate to severe
      ABI. SETTINGS: Outpatient, community-based, and residential rehabilitation
      facilities for persons with ABI located in the United States: West, Midwest, and
      Southeast. METHODS: Rasch, item cluster, principal components, and traditional
      psychometric analyses for internal consistency of MPAI data and subscales.
      RESULTS: With rescoring of rating scales for 4 items, a 29-item version of the
      MPAI showed satisfactory internal consistency by Rasch (Person Reliability=.88;
      Item Reliability=.99) and traditional psychometric indicators (Cronbach's
      alpha=.89). Three rationally derived subscales for Ability, Activity, and
      Participation demonstrated psychometric properties that were equivalent to
      subscales derived empirically through item cluster and factor analyses. For the 3
      subscales, Person Reliability ranged from.78 to.79; Item Reliability, from.98
      to.99; and Cronbach's alpha, from.76 to.83. Subscales correlated moderately
      (Pearson r =.49-.65) with each other and strongly with the overall scale (Pearson
      r=.82-.86). CONCLUSIONS: Outcome after ABI is represented by the unitary
      dimension described by the MPAI. MPAI subscales further define regions of this
      dimension that may be useful for evaluation of clinical cases and program
      evaluation.

PMID- 14707879
TI  - Brain imaging as a predictor of early functional outcome following traumatic
      brain injury in children, adolescents, and young adults.
AB  - OBJECTIVES: A depth of lesion (DOL) model using brain imaging has been proposed
      to aid in medical decision-making and planning for rehabilitation resource needs.
      The purpose of this study was to determine the early prognostic value of a DOL
      classification system for children and young adults following severe traumatic
      brain injury. METHODS AND OUTCOME MEASURES: CT/MRI brain imaging studies on 92
      patients, aged 3 to 21, admitted to the Kluge Children's Rehabilitation Center,
      University of Virginia, were evaluated to determine DOL. Images were classified
      according to 5 DOL levels (cortical to brainstem). Functional outcomes in
      mobility, self-care, and cognition, as rated on the WeeFIM instrument, were
      compared by DOL levels. RESULTS: Admission WeeFIM scores were significantly
      different for the DOL levels with the highest score for frontal and/or temporal
      lesions and the lowest for lesions including the brainstem or cerebellum
      (P<.001). However, the deeper the lesion, the greater the functional gains
      (P=.05), resulting in discharge WeeFIM scores that were not significantly
      different across DOL levels. Patients with deeper lesions tended to have longer
      lengths of stay in rehabilitation but were able to "catch up" with patients who
      had more superficial lesions. CONCLUSIONS: While relatively simple and
      convenient, the DOL classification system is limited in its usefulness as an
      early prognostic tool. It may not be possible to predict outcome in the early
      acute phase in the intensive care unit on the basis of standard brain imaging
      alone. Patients with deeper lesions may enter rehabilitation at a more impaired
      level but can make remarkable progress, though it may take longer than for less
      severely injured individuals.

PMID- 14707880
TI  - The use of a World Wide Web-based consultation site to provide support to
      telephone staff in a traumatic brain injury demonstration project.
AB  - OBJECTIVES: Distance from expertise in traumatic brain injury (TBI) is often an
      impediment to appropriate TBI care from local health care providers, especially
      in rural areas. To overcome this barrier to care and to support a randomized,
      controlled trial of telephone follow-up after discharge from acute
      rehabilitation, we demonstrated the use of a confidential consultation Web site
      to provide expert recommendations and advice to front-line telephone staff at a
      different site. CONCLUSIONS: This use of Internet communication proved convenient
      to all users, improved client confidence, and served as an excellent training
      tool to less experienced staff. In addition, use of a Web-based consultation
      method provided for archiving of all discussions for later review.

PMID- 14707881
TI  - Residual effects of a traumatic brain injury on locomotor capacity: a first study
      of spatiotemporal patterns during unobstructed and obstructed walking.
AB  - OBJECTIVES: To understand the residual locomotor effects of a traumatic brain
      injury (TBI) on unobstructed and obstructed walking. PARTICIPANTS: Eight young,
      high-functioning adults with TBI and 4 healthy subjects. MAIN OUTCOME MEASURES:
      Spatiotemporal gait parameters and their relation to specific clinical measures
      of severity and locomotor and balance abilities. RESULTS: Subjects with TBI
      walked slower and showed a tendency for greater foot clearances in all
      conditions. Slower walking was due to decreased stride lengths and not cadence,
      while higher foot clearances were due to placing the trailing foot farther from
      the obstacle and increasing hip flexion angles during avoidance. CONCLUSIONS: The
      results suggest that this highly functional TBI population used increased
      caution. Measures of injury severity did not provide simple predictions of
      locomotor ability, but the one-legged stance test with eyes closed correlated to
      walking capacity.

PMID- 14707882
TI  - Interrater reliability of the TEMPA for the measurement of upper limb function in
      adults with traumatic brain injury.
AB  - OBJECTIVE: To investigate the interrater reliability of the TEMPA in adults with
      traumatic brain injury (TBI). PARTICIPANTS: Twenty adults with upper limb
      dysfunction after TBI who were participating in inpatient rehabilitation. DESIGN:
      The TEMPA assessment was videotaped for each participant and 5 physical
      therapists independently rated these video recordings. MAIN OUTCOME MEASURE:
      Functional rating and speed of execution for each item of the TEMPA. RESULTS:
      Intraclass correlation coefficients (ICC) for the speed of execution and
      functional rating components of the TEMPA ranged from 0.898 to 1.000. CONCLUSION:
      The excellent interrater reliability supports the use of the TEMPA in adults with
      TBI.

PMID- 14707883
TI  - Outcome of memory rehabilitation in traumatic brain injury assessed by
      neuropsychological tests and questionnaires.
AB  - OBJECTIVES: To evaluate the effectiveness of a memory rehabilitation program. To
      compare different outcome measures. PARTICIPANTS: Twelve patients with severe
      traumatic brain injury. SETTING: Outpatient rehabilitation service. MAIN OUTCOME
      MEASURES: Rey-Osterrieth Complex Figure Test (REY), California Verbal Learning
      Test (CVLT), Rivermead Behavioural Memory Test (RBMT), and the Memory Failures in
      Everyday Memory Questionnaire (MFE). STATISTICAL ANALYSIS: Exact nonparametric
      procedures. RESULTS: All patients achieved meaningful functional gains. Modest
      improvements were found in some of the scales of the CVLT but not in the REY,
      RBMT, or MFE. CONCLUSION: Functional gains did not correlate with improvement in
      memory processes. Measurement of changes in independence in activities of daily
      living mediated by compensatory aids and educational intervention plans with
      relatives are proposed.

PMID- 14707884
TI  - Anterior pituitary dysfunction after traumatic brain injury, Part I.

PMID- 14707885
TI  - Positive and negative regulation of glucose uptake by hyperosmotic stress.
AB  - This review will provide insight on the current understanding of the
      intracellular signaling mechanisms by which hyperosmolarity mimics insulin
      responses such as Glut 4 translocation and glucose transport but also antagonizes
      insulin effects. Glucose uptake induced by insulin is largely dependent on the PI
      3-kinase/PKB pathway. In both adipocyte and muscle cells, hyperosmolarity
      promotes glucose uptake by multiple mechanisms which do not require PI 3
      kinase/PKB pathway but are dependent on the cell type. In muscle, osmotic stress
      induces glucose uptake by stimulation of AMP-Kinase and/or inhibition of Glut 4
      endocytosis. In adipocytes, activation of Gab1-dependent signaling pathway plays
      an important role in osmotic stress-mediated glucose uptake. Apart of its insulin
      like effects, hyperosmolarity can lead to cellular insulin resistance mediated by
      both prevention of PKB activation and inhibition of the Insulin Receptor
      Substrate-1 (IRS1) function. Serine phosphorylation and degradation of IRS1
      negatively regulate its functions. Understanding how osmotic stress induces
      glucose transport or mediates insulin resistance may provide novel targets for
      strategies to enhance glucose transport or to prevent insulin resistance.

PMID- 14707886
TI  - Oxidative stress as a therapeutic target in diabetes: revisiting the controversy.
AB  - Oxidative stress has been repetitively shown to be a hallmark of many diseases
      linked with metabolic or vascular disorders. Therefore diabetes represents an
      ideal candidate for studying the consequences of oxidative stress and its
      treatment. Indeed diabetes constitutes a multiple source of free radicals,
      starting very early in the disease process and worsening over the course of
      disease. In view of the typical characteristics of diabetes, oxidative stress is
      expected to have a double impact, on both metabolic and vascular functions. It is
      therefore particularly disappointing to note the dramatic failure of clinical
      trials with antioxidants, although it must be pointed out that such studies have
      not been performed with only diabetic patients. This review describes the many
      different aspects of oxidative stress in diabetes and proposes possible
      explanations for the apparent lack of efficacy of antioxidant treatments in
      patients. Some verifications seem warranted before a definitive conclusion can be
      drawn about the validity of this therapeutic concept.

PMID- 14707887
TI  - Self-monitoring of blood glucose significantly improves metabolic control in
      patients with type 2 diabetes mellitus: the Auto-Surveillance Intervention Active
      (ASIA) study.
AB  - OBJECTIVE: Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic
      of current interest (imbalance between increased health-care costs and
      improvement in compliance with treatment and diet). An open label randomized
      prospective study was designed to compare changes in metabolic control over 6
      months in patients managed with usual recommendations alone (conventional
      assessment group) or combined with SMBG. RESEARCH DESIGN AND METHODS: Patients
      not treated with insulin or previously self monitored, 40 to 75 years of age,
      with a diagnosis of type 2 diabetes > 1 year and standardized HbA(1c) level >
      =7.5 and< =11% were randomized to either a control group or SMBG group. They were
      followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given
      the same device (Ascensia Esprit Discmeter, Bayer) and were required to perform
      at least 6 capillary assays a week (3 different days of the week, including
      weekend). Management of patients was standardized, including drugs, diet and
      physical activity. The primary efficacy criterion was change in HbA(1c) level in
      Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6
      months using the calibrated DCA 2000(R) device (Bayer). RESULTS: Two hundred
      sixty five general practitioners randomized 988 patients (ITT Population), but
      689 patients were evaluable for the primary criterion. At the endpoint, HbA(1c)
      was lower in the SMBG group (8.1 +/- 1.6%) than in the conventional treatment
      group (8.4 +/- 1.4%, P=0.012). The change in HbA(1c) levels between baseline and
      endpoint was classified into two classes: improvement if a change > 0.5%
      occurred, stability or worsening in case of a change< =0.5%; 57.1% of patients in
      the SMBG group vs 46.8% in the control group had an improvement in HbA(1c) level
      (P=0.007) after 3 months. A steady state was reached during the last 3 months. A
      multivariate logistic regression analysis was performed and identified factors
      predictive of improvement in HbA(1c) levels: HbA(1c) at baseline: odd ratio
      (OR)=1.749 (P<0.001), SMBG group (reference value: SMBG group): OR=0.665
      (P=0.015), duration of diabetes: OR=0.953 (P=0.001) and BMI: OR=0.962 (P=0.039).
      CONCLUSIONS: This study is the first multicenter, controlled, prospective trial
      conducted on a large number of patients demonstrating that SMBG was statistically
      associated with a better quality of metabolic control than usual traditional
      recommendations alone in type 2 diabetes.

PMID- 14707888
TI  - Kinetics of diabetes-associated autoantibodies after sequential intraportal islet
      allograft associated with kidney transplantation in type 1 diabetes.
AB  - OBJECTIVE: Presence or occurrence of pancreas auto-antibodies (aAb) has been
      shown to be of poor prognosis for islet cell transplantation. The aim of the
      study was to monitor the kinetics of these aAb after sequential intra-portal
      islet plus kidney transplantation with pre-Edmonton immunosuppressive regimen in
      order to determine whether the sequential protocol of transplantation was
      involved in the occurrence of the immune response. PATIENTS AND METHODS: Three
      patients with IDDM and a previous (IAK) or simultaneous (SIK) kidney
      transplantation received 3 or 4 ABO compatible islet preparations. Islets (> 8
      000 IEQ/kg post culture) were sequentially transplanted within a 12 day period
      via a per-cutaneous catheter. Immunosuppressive treatment included cyclosporine,
      steroids and mycophenolate. Plasma ICAs, GAD 65, IA2 and C peptide (C-p) levels
      were monitored. Type II HLA phenotype was determined in donors and recipients.
      RESULTS: Patient #1 had high anti-GAD levels (26.5 UI/l) before the IAK, while
      anti-IA2 and ICA levels were low. After the transplantation, C-p levels increased
      to 4.9 ng/ml at one month before becoming undetectable at 2 months. GAD levels
      remained high, ICA and IA2 aAb were undetectable. Patients #2 and #3 did not have
      significant levels of aAb before the islet transplantation. A slight increase in
      GAD was observed with each islet transplantation, followed by an overt but
      transient increase in ICA. IA2 levels remained undetectable. Three months after
      the transplantation and 2 weeks after the increase of ICA, C-p levels, that were
      >3.4 ng/ml at one month, fell below 0.2 (N: 0.5-2). CONCLUSION: The
      immunosuppressive regimen used in kidney transplantation is unable to control
      perfectly anti-pancreas aAb production. Moreover, these results seem to indicate
      that the benefits of sequential islet transplantation lie more in the increased
      islet mass they provide than in potential immune benefit.

PMID- 14707889
TI  - Combined improvements in implantable pump technology and insulin stability allow
      safe and effective long term intraperitoneal insulin delivery in type 1 diabetic
      patients: the EVADIAC experience.
AB  - OBJECTIVE: To report a long-term multicentre experience with implantable insulin
      pumps in type 1 diabetic patients, and to test safety and accuracy of the systems
      following improvements in infused insulin solutions and peritoneal catheter.
      RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were
      consecutively implanted over a two-month period in type 1 diabetic volunteers.
      The systems were equipped by a new compliant sideport catheter and were refilled
      at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical
      stability in vitro. Safety was assessed from the incidence of acute adverse
      events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was
      measured at each pump refill by comparing residual insulin in the pump reservoir
      with expected amount according to programmed infusion. The study lasted until
      pump battery depletion or premature pump explantation. RESULTS: Cumulated
      experience was 106 patient-years. Premature explantations occurred in 3 cases,
      due to one electronic pump failure and two "pump-pocket" infections. Near-normal
      insulin delivery was sustained until expected battery depletion in 13 cases.
      Forty underdelivery events occurred in 24 pumps, but 36 among them were related
      to pump slowdowns due to insulin aggregation in pumps that were promptly solved
      by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by
      catheter obstructions that required laparoscopy to remove peritoneal tissue
      overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in
      the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only
      one severe hypoglycemia and one ketoacidosis occurred during the whole study.
      CONCLUSION: Our current experience with improved implantable pumps and insulin
      solutions shows both long-term safety and effectiveness of this treatment in type
      1 diabetic patients following improvement in infused insulin solutions and
      catheter. This therapy may be a good alternative for patients that experience
      frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

PMID- 14707890
TI  - Improved metabolic control in diabetic adolescents using the continuous glucose
      monitoring system (CGMS).
AB  - OBJECTIVE: To determine the utility of the continuous glucose monitoring system
      (CGMS) as an outpatient procedure to improve management of diabetes in
      adolescents. RESEARCH DESIGN AND METHODS: Twelve adolescents (mean age: 16.2 +/-
      3 years) with poorly controlled type 1 diabetes (HbA(1c) > 8%) were included in
      this trial. Mean HbA(1c) during the previous year was 10.1 +/- 1.2%. Insulin
      treatment consisted of 2 or 3 daily injections in 10 cases and CSII in 2. At the
      beginning of the study, HbA(1c) was determined and low blood glucose index (LBGI)
      was calculated. Continuous glucose monitoring was performed for three days. After
      downloading and analyzing data, results were discussed with the patient and
      insulin treatment was adjusted. Two months later testing was repeated and all
      parameters were reassessed. RESULTS: Initial CGMS profiles demonstrated glycemic
      excursions unrecognized by capillary measurements in all twelve patients.
      Glycemia before and after meals varied from<60 mg/dL to > 200 mg/dL in 2 patients
      (2 episodes). Postprandial hyperglycemia exceeded 200 mg/dL in 10 patients (24
      episodes). Prolonged overnight hyperglycemia was observed in 5 patients (7
      episodes), dawn phenomenon in 4 patients (6 episodes) and nighttime hypoglycemia
      in 4 patients (4 episodes). A day-to-day reproducibility of glycemic profiles was
      observed in 8 patients. Then insulin treatment was adjusted according to CGMS
      data. Changes involved dose levels in 3 patients, insulin type in 7, number of
      injections, i.e. 3 instead of 2, in 5 or change from insulin injection to CSII in
      1. Reassessment two months later demonstrated a significant reduction of glycemic
      excursions in 8 patients. HbA(1c) (m +/- SD) decreased from 10.3 +/- 2.1% to 8.75
      +/- 1.06% (p<0.05). LBGI increased from 1.7 +/- 0.9 to 2.4 +/- 1.4 but the
      difference was not significant. CONCLUSIONS: Use of CGMS in diabetic adolescent
      outpatients achieved a significant improvement in metabolic control not only by
      providing accurate data for adjustment of insulin treatment but also by promoting
      patient communication and motivation.

PMID- 14707891
TI  - The effect of micronised fenofibrate on paraoxonase activity in patients with
      coronary heart disease.
AB  - OBJECTIVE: To evaluate the effect of micronised fenofibrate on serum paraoxonase
      (PON) and lipoprotein levels in coronary heart disease patients with type IIb
      hyperlipidemia. PATIENTS AND METHODS: Fifty-two patients were investigated for
      the three-month effect of 200 mg per day micronised fenofibrate on the serum
      enzyme activity and concentration of PON and their relationship with serum
      lipids, high-density lipoprotein (HDL-C) parameters. RESULTS: Serum paraoxonase
      activity was lower in CHD patients with type IIb hyperlipoproteinemia. During the
      three-month study it was observed that following treatment with micronised
      fenofibrate, serum triglyceride and cholesterol levels decreased, while HDL-C
      increased significantly (p<0.001). Low-density lipoprotein (p<0.05) and
      apolipoprotein B-100 (p<0.01) decreased, while HDL constituent apolipoprotein A-I
      (p<0.05) increased after micronised fenofibrate treatment. The HDL-associated
      paraoxonase specific activity increased significantly (p<0.05). To assess whether
      the increased PON activity was due to elevated HDL and apoA-I level, we
      standardized PON activity for HDL and apoA-I concentrations. The standardized
      values for HDL (PON/HDL) increased (p<0.05) while the PON/apoA-I ratio did not
      change significantly. CONCLUSION: Three months of treatment with micronised
      fenofibrate is thought to normalize lipid profile and improve antioxidant status
      by increasing serum paraoxonase activity in these patients.

PMID- 14707892
TI  - The use of information technology for the management of intensive insulin therapy
      in type 1 diabetes mellitus.
AB  - OBJECTIVE: The purpose of the study was to evaluate the safety of a computer
      program used by the patient for the adjustment of insulin doses to achieve tight
      glycemic control in type 1 diabetic subjects on intensive insulin therapy.
      METHODS: Ten type 1 diabetic patients participated in the study. Using the basal
      bolus (UL-Humalog) insulin regimen, they were randomized in a crossover design to
      2 intensive treatment periods of 8 weeks each, one with and the other without the
      assistance of a computer program via the Internet. They measured their capillary
      blood glucose regularly, and the results were entered on a daily basis into their
      log-book or in the computer. During intensive treatment with the computer, the
      software would provide recommendation for insulin dose adjustment according to
      specific algorithms. When on intensive treatment without computer assistance,
      they would adjust their own insulin dose according to the same algorithms.
      RESULTS: The study subjects followed 89% of the recommendations made by the
      computer. With the computer, subjects made more insulin dose adjustments (98
      versus 50) than without. Intensive treatments with and without computer
      assistance resulted in a similar improvement of pre-meal/post-prandial capillary
      blood glucose from 7.6 +/- 2.7/9.5 +/- 2.5 to 6.7 +/- 2.3/8.8 +/- 2.5 and 6.7 +/-
      2.6/9.0 +/- 2.6 mmol/L, respectively. Glygated hemoglobin also improved from 7.7
      +/- 0.9% to 7.2 +/- 0.7 and 7.3 +/- 0.8%, respectively. The incidence of minor
      hypoglycemia was similar under both intensive treatments (7.9 +/- 4.0 and 7.1 +/-
      5.0/patient/28 days, respectively). Both treatments increased patient behavior
      while patient knowledge of their disease was improved only during computer
      assistance. There was no effect on quality of life. The study subjects greatly
      appreciated the software and wanted to continue using it. CONCLUSIONS: The study
      demonstrated that the use of computer software by the patient to adjust insulin
      doses for intensive insulin therapy is feasible and is not associated with
      increased adverse events.

PMID- 14707893
TI  - Amputations among diabetics in Reunion Island.
AB  - OBJECTIVES: Our study allowed us to exhaustively list up all the cases of lower
      limb amputation carried out in the hospitals of the island from May 1st, 2000 to
      April 30, 2001. METHODS: We studied the medical files of all the diabetic
      patients having undergone a non traumatic amputation and they all had an
      interview with an inquiring doctor. RESULTS: 406 amputations (including 11
      traumatic ones) have been carried out over the 12 months of our study. On a total
      of 395 non traumatic amputations, 70% were made among diabetics and concerned 278
      patients among whom 179 are type 2 diabetics. Men are more concerned than women.
      If the distribution of amputation levels does not differ between diabetics and
      non-diabetics, the former more often undergo multiple interventions. 72% of the
      patients have a level of primary education, 59% have difficulties reading, and
      most of them have a very limited knowledge on their disease and do not practise
      any prevention for podologic traumatism. CONCLUSION: In a region where 718 220
      inhabitants live and where the rate of diabetes prevalence is high (17.7% for 30
      69 years), we could be afraid for the years to come of an important increase of
      the prevalence and diabetes chronic complications incidence rates. Authorities
      have to become aware of the current risks and of increasing equipments and
      personnel for the prevention and the follow-up of this insidious pathology.
      Programmes for the prevention of podologic complications should be supported by
      taking into account local specificities.

PMID- 14707894
TI  - Fish-seafood consumption, obesity, and risk of type 2 diabetes: an ecological
      study.
AB  - OBJECTIVES: There is substantial evidence that type 2 diabetes increases with the
      degree and duration of obesity. This study was conducted to examine the
      association, at the international level, between fish and seafood consumption and
      the prevalence of type 2 diabetes, taking into account the prevalence of obesity.
      METHODS: An ecological study of 41 countries in five continents with different
      socio-demographic characteristics and sanitary conditions was carried out. Data
      on the prevalence of diabetes and obesity as well as food balance sheets were
      collected from websites. Correlations between the variables studied were followed
      by an exploration of their interaction. RESULTS: After adjustment for total
      energy intake, there was a significant correlation (rho=0.81, P<0.0001) between
      the prevalence of type 2 diabetes in the 20- to 44- and 45- to 64-year age
      groups. Type 2 diabetes in the 45- to 64-year age group was about 5 times higher
      than in the 20- to 44-year age group. Obesity was positively associated with type
      2 diabetes in both age groups (rho=0.39; P=0.012 and rho=0.48; P=0.002 in the 20-
      to 44- and 45- to 64-year age groups, respectively). An interaction effect was
      found between diabetes, obesity and total fish and seafood consumption. In
      countries with low fish and seafood consumption, the prevalence of type 2
      diabetes increased significantly with obesity (0.8 +/- 0.3% vs. 2.5 +/- 1.8%;
      P=0.002 and 3.3 +/- 2.6% vs. 11.0 +/- 3.9%; P<0.0001 for the 20- to 44- and 45-
      to 64-year age groups, respectively). In countries with a greater prevalence of
      obesity, there was evidence of significantly reduced type 2 diabetes with high
      fish and seafood consumption (2.5 +/- 1.8% vs. 0.9 +/- 0.7%; P=0.007 and 11.0 +/-
      3.9% vs. 6.2 +/- 4.1%; P=0.041 for the 20- to 44- and 45- to 64-year age groups,
      respectively). CONCLUSION: The results of this study suggest that high fish and
      seafood intake may reduce the risk of type 2 diabetes in populations with a high
      prevalence of obesity.

PMID- 14707895
TI  - Evaluation of hepatic and whole body glycogen metabolism in humans during
      repeated administrations of small loads of 13C glucose.
AB  - BACKGROUND: Postprandial suppression of endogenous glucose production and
      regulation of glucose homeostasis involve alterations of whole body and hepatic
      glycogenolysis and glycogen breakdown. These parameters can be estimated by the
      simultaneous measurement of net total and exogenous, (13)C-labeled, glucose
      oxidation. METHODS: Eight subjects were studied on 3 occasions, while receiving
      oral loads of 60 mg, 120 or 180 mg (13)C glucose/kg every hour for 4 consecutive
      hours. Net glucose oxidation was calculated from indirect calorimetry, and
      exogenous glucose oxidation from (13)CO(2) production. These parameters were
      evaluated during the hour following the fourth glucose load. Whole body
      endogenous glycogen breakdown was calculated as (net glucose oxidation) -
      (exogenous glucose oxidation). Total glycogen synthesis was calculated as
      (glucose load) - (exogenous glucose oxidation). Whole body glucose turnover was
      measured with 6.6 (2)H(2) glucose. The systemic appearance of oral, (13)C labeled
      glucose was monitored, and the suppression of endogenous glucose production was
      calculated. RESULTS: Plasma glucose tracers had reached near steady state during
      the hour following the fourth glucose load. Glucose ingestion dose-dependently
      suppressed endogenous glycogen breakdown and stimulated total glycogen synthesis.
      Endogenous glycogen breakdown was completely inhibited with 180 mg oral
      glucose/kg. Endogenous glucose production was suppressed in a dose-dependent way,
      but remained positive with all 3 doses. The first pass splanchnic glucose uptake
      averaged 25-35%. CONCLUSION: Repeated administration of small doses of (13)C
      labeled glucose allow to reach near steady state conditions after four hours, and
      to non-invasively evaluate whole body glycogen turnover and hepatic glucose
      metabolism.

PMID- 14707896
TI  - [Prevention of type 1 diabetes: what have we achieved? What should we say and
      propose next to families?].
AB  - Prevention of type 1 diabetes in high risk individuals presents with both
      positive and negative aspects. On one hand, the availability of reliable and
      convenient screening tools (antibodies) allows us to quantify the risk of
      diabetes in the short term. Large randomised studies have provided indisputable
      answers regarding the efficiency of selection of at risk patients. Unfortunately,
      both DPT-1 study (using insulin) and ENDIT trial (with nicotinamide) ruined the
      hopes raised from solid experimental data. These studies have also demonstrated
      the huge costs in terms of number of subjects, time for follow-up, and financial
      burden, requiring an international collaboration. Finally, only a small number of
      such studies can be conducted simultaneously. Progress and obstacles paving this
      research area must be explained to diabetic patients and their family. Current
      mitigated results should not drive us to give up screening campaigns. Rather,
      these results should prompt diabetes centers and families to participate in the
      selection of high risk individuals in order to explore new therapeutic options
      within future prevention trials.

PMID- 14707898
TI  - [From obesity to obesities: from concepts to practices].
AB  - In the singular, obesity is a symptom reflecting an excess of energy stores as
      fat mass, the only trait obese people are sharing. Long time ago we proposed to
      use the plural to account for the large diversity characterizing obese subjects
      that conceptual evolutions have put to the fore during the past three decades.
      Weight gain and obesity are resulting from a positive energy balance produced by
      the conjunction of a number of etiopathogenetic factors associated in various
      proportions according to patients and evolutive status. Decreasing physical
      activity, increasing sedentarity, quantitative and qualitative energy consumption
      unadapted to energy expenditure and to lipid oxidation capabilities, reinforced
      by psychological needs, are catching out the control of food intake, particularly
      since it is more efficient to defend against famine than to protect against
      plethora. These environmental factors, responsible for obesity pandemia, lead to
      obesity subjects predisposed by their genetic background, in itself extremely
      variable. The clinical heterogeneity of obesity is patent and a careful
      phenotypic analysis is a prerequisite to design the management strategy. Obesity
      is a chronic situation that needs a long-term treatment. The goals of treatment
      cannot be longer reduced to weight loss only, which in addition should be
      realistic, i.e. moderate. Management strategies must be conceived on a long-term
      basis, focused on prevention of weight regain, multifaceted and individually
      tailored. A number of tools are available and the state of the art is to use them
      appropriately to avoid being counter productive. Obesity may be viewed as an
      adaptive symptom in subjects poorly prepared to cope with recent environmental
      changes, but it is also a disease due to its prevalence, the number of weight
      dependent comorbidities and its socio economic costs. A specific medical approach
      of obesity has still to be developed.

PMID- 14707900
TI  - [How to define and to analyse troubles of eating behaviours?].
AB  - Eating disorders are frequent in obese patients, and often underreported.
      However, it is mandatory to diagnose and to assess them, as therapeutic
      management of these eating disorders should precede weight loss attempts. We
      describe the main eating disorders, their diagnosis and assessment, as well as
      the important steps of the management strategy, in which cognitive-behavioural
      therapy should play a major role.

PMID- 14707899
TI  - [Plastic surgery and obesity: why, when, how?].
AB  - In this review, we describe the main surgical procedures used in the plastic
      surgery of obesity: lipectomies and removal of excess fat tissues after weight
      loss, liposuction of localised fat deposits, surgery of breast hypertrophies. The
      main surgical procedures, their indications, their techniques and their long-term
      results are described. Such surgery should be part of a coherent and structured
      therapeutic project, defined together with the patient. The management and follow
      up should be maintained on the long term after the initial weight loss and the
      surgical procedure, in order to reinforce the benefit and to prevent a weight
      regain.

PMID- 14707901
TI  - [Locomotor handicap and obesity].
AB  - Obesity and osteoarthritis are frequently associated, particularly in older
      patients. Obesity increases the relative risk to develop knee or hip
      osteoarthritis, mainly in case of early obesity. This relative risk to develop
      osteoarthritis increases with body mass index, particularly in women. Early
      management of obesity, even a moderate weight loss, decreases the risk to develop
      knee osteoarthritis. Therapeutic management of obese patients is not different
      from those of non-obese patients; however, it is essential to integrate weight
      loss within the therapeutic project. Obesity should not be a contraindication to
      total knee or hip replacement, but weight loss has to be part of the pre- and
      post surgical management program of the obese patient.

PMID- 14707902
TI  - [Management of childhood obesity].
AB  - The prevalence of obesity is currently increasing in children and young
      adolescents in France, and affects about 10 to 14% of them. Therapeutic
      objectives should aim to improve, on the long-term, the weight/body mass index
      curve. Restrictive diet and weight loss should not be the primary target. The
      focus has to be on a balanced healthy diet, tailored to children growth,
      associated with a regular physical activity. Children weight management should be
      within the usual life conditions, taking into account familial and social
      environmental conditions, through a multidisciplinary team approach as those
      implemented in our paediatric medical centre. The objectives, management steps
      and current results of our therapeutic educational project are described.

PMID- 14707903
TI  - [Obesity and inflammation: the adipocytokines].
AB  - It is now well documented that obesity is associated with a chronic, low grade,
      inflammatory state. The serum concentrations of a number of inflammatory markers,
      such as CRP, fibrinogene or serum amyloids are increased in obese subjects. More
      importantly, the levels of several pro-inflammatory cytokines, including
      TNFalpha, IL-6 and leptin are significantly higher in the plasma of obese
      patients. We will review here the possible role of adipose tissue and the
      production of adipocyte-derived cytokines in this inflammatory state. The
      observed increase in the concentrations of these adipocytokines is now suspected
      to play a determinant role in the development of most of the complications of
      obesity.

PMID- 14707904
TI  - [Should the prevention of obesity be demedicalised?].
AB  - Obesity prevalence is rapidly growing, particularly in children and young
      adolescents. It is proved to be important to prevent it within a public health
      strategy. Primary prevention of obesity should not be focused on obesity itself,
      but should be part of a global public health national policy, targeted to improve
      the nutritional status of the community, to reduce the risk for chronic diseases,
      to improve the health status and the quality of life of the general population.
      This overall prevention programme should be conducted on a large scale, at all
      level of the country infrastructure and sectors of society, and should acquired a
      strong local and regional support from communities, consumers and government, but
      it has also to be particularly focused on young subjects (and their family and
      school workers), especially in groups with low socio-economic status. Secondary
      prevention should be particularly focused on children with a high-risk for
      obesity and/or those with potential associated risk factors. Medical involvement
      is of a particular importance in this secondary prevention, to identify and to
      manage these at-risk children and young adolescents. The various approaches from
      a paediatrician, a physician specialised in human nutrition, a sociologist and a
      consumer representative are presented in this review.

PMID- 14707906
TI  - [Status of current adjuvant therapies in NSCLC].

PMID- 14707907
TI  - [Neoadjuvant approach to NSCLC].

PMID- 14707908
TI  - [Chemoradiation therapy optimization for stage III NSCLC].

PMID- 14707909
TI  - [Do the new drugs improve therapeutic strategies for stage IV NSCLC?].

PMID- 14707910
TI  - [Do the new drugs improve prognosis of stage IV NSCLC?].

PMID- 14707911
TI  - [Post-surgical NSCLC follow up].

PMID- 14707912
TI  - [Interventional endoscopy: clearing of airways in thoracic cancer].

PMID- 14707913
TI  - [New therapeutic progress in chemotherapy for mesothelioma].

PMID- 14707914
TI  - [Pneumonic-type adenocarcinoma].

PMID- 14707915
TI  - [Germ cell tumors of the mediastinum].

PMID- 14707916
TI  - [Contribution of ASCO 2003 to our clinical practice in NSCLC].

PMID- 14707917
TI  - [Targeted biological treatments: hopes and disappointments].

PMID- 14707918
TI  - [Lung cancer in elderly patients: definition and therapeutic approach].

PMID- 14707920
TI  - [Impact of economic criteria on clinical decisions].

PMID- 14707919
TI  - [Lung cancer among French women in 2000: results of an epidemiological study (KBP
      2000)].

PMID- 14707921
TI  - [From chemoprevention to early screening].

PMID- 14707922
TI  - [Responsibility of the tobacco industry regarding the smoking pandemia].

PMID- 14707923
TI  - [[18F]-FDG imaging in apparently isolated pleural lesions].
AB  - While a great deal of work has been performed concerning the impact of [18F]-FDG
      imaging in isolated lung lesion(s), there are still very few data about its role
      in case of isolated pleural lesions. The aim of this preliminary study was to
      shed some light on the utility of [18F]-FDG imaging, using PET or CDET detection,
      in this context. PATIENTS AND METHOD: Sixteen patients referred for apparently
      isolated pleural lesions were included in this study, since their 22 [18F]-FDG
      examinations were evaluable on bases of histology (9 cases), rapid disease
      progression (4 cases) or a follow-up period of more than 6 months (9 cases).
      Twelve [18F]-FDG examinations were performed with a dedicated PET machine (C-PET,
      Adac) and ten with a coincidence detection gamma camera (Irix, Picker). The
      precise clinical settings were the following: characterization of pleural masses
      or search for the unknown primary tumor in case of adenocarcinoma (6 cases),
      staging of a mesothelioma (5 cases), suspicion of recurrence and/or residual
      lesions (11 cases). RESULTS: The malignant pleural lesions took up [18F]-FDG in
      all cases. There was one false positive result due to an inflammatory lesion.
      False negative results for the detection of lymph node invasion occurred in three
      patients and were in relation with their infracentimetric size and the difficulty
      to distinguish on [18F]-FDG images mediastinal lymph nodes from widespread
      pleural and pulmonary extension of cancer. A change in patient management
      resulted from the [18F]-FDG examination in 4 patients (25%) and the course
      confirmed that the change was correct. Unknown lesions or active lesions wrongly
      considered residual that could have modified the management were discovered in 3
      other patients. CONCLUSIONS: This study highlights the fact that [18F]-FDG
      imaging has an impact on the management of patients with solitary pleural lesions
      and can detect recurrences, in some cases even more accurately than invasive
      procedures with histology. In our limited experience, the lack of anatomical
      details of the PET images is a major drawback in this setting and we are
      convinced that PET-CT will substantially enhance the impact of [18F]-FDG imaging.

PMID- 14707924
TI  - [Drug and non-drug strategies for smoking cessation. AFSSAPS guidelines].

PMID- 14707925
TI  - [Herpes simplex and Geotrichum candidum pneumonia in a patient with moderate
      renal failure].
AB  - Viral or fungal pneumonia generally occurs in immunocompromised patients. We
      report a case of hypoxic pneumonia unresponsive to broad-spectrum antibiotic
      therapy in a patient whose only risk factor for immunodeficiency was mild silent
      renal failure. The causal association between Herpes simplex and Geotrichum
      candidum was retained on the basis of endobronchial samples and the favorable
      course after institution of specific treatment. It is thus useful to consider
      these pathogens in patients with lung infection in order to institute specific
      treatment.

PMID- 14707926
TI  - ["Spontaneous" resolution of two severe methotrexate-induced pneumonias].
AB  - The beneficial role of corticosteroid therapy for the treatment of methotrexate
      induced pneumonia remains controversial. We report two cases of acute severe
      interstitial pneumonia induced by methotrexate in patients with non-Hodgkin
      lymphoma given a polychemotherapy protocol (M'BACOD). The first signs appeared on
      the eleventh day of the first cycle in patient one and on the tenth day of the
      third cycle in patient two. The causal implication of methotrexate was based on
      the history, the clinical and radiological presentation, and the negative tests
      in both patients: lymphocyte alveolitis with granulomatous lesions on the
      transbronchial biopsy in patient one and positive leukocyte migration test in the
      presence of methotrexate in patient two. Early acute respiratory failure required
      high flow rate oxygen therapy with positive expiratory pressure ventilatory
      assistance. The course was rapidly favorable both for blood gases and
      radiographic presentation without corticosteroids. These two cases illustrate
      that pulmonary disease can be cured without corticosteroids despite severe
      respiratory failure at onset. This provides a further argument on reservations
      about using corticosteroids for suspected methotrexate-induced pneumonia.

PMID- 14707927
TI  - [A rare cause of posterior mediastinal tumors: extramedullary hematopoiesis].
AB  - We report a case of a patient with intrathoracic extramedullary hematopoiesis
      presenting as a posterior mediastinal tumor, without associated myelofibrosis.
      Pathophysiology and the options for diagnosis and treatment in this condition are
      discussed.

PMID- 14707928
TI  - [Intrapulmonary rupture of a dermoid cyst: MRI findings].
AB  - We report a case of dermoid cyst of the mediastinum ruptured into the lung. Only
      a few reports of ruptured mediastinal dermoid cyst have appeared in the
      literature. A 18-year-old female patient developed a tumor in the anterior
      mediastinum, which was coincidentally detected by a conventional chest X-ray. CT
      and MRI demonstrated two components: a cystic mediastinal mass and adjacent
      parenchymatous condensation. The cystic mass (no enhancement during or after
      injection) had a fatty structure: high-intensity T1 signal and low-intensity T2
      signal. The thin wall (low-intensity signal on T1 and T2) was strongly enhanced
      during the systemic time and was ruptured. The parenchymatous condensation
      included a fatty effusion and an inflammatory reaction with the same T1 signal as
      the cyst, remaining slightly hyperintense on T2 with enhancement after injection.
      Cine-MRI demonstrated that the mass and the compressed right atrium were
      independent.

PMID- 14707929
TI  - [Aorticopulmonary paraganglioma. A case report].
AB  - Paraganglioma is a tumor which develops from the paraganglion system, generally
      in the adrenal medulla (90%). Thoracic localisations are exceptional and arise
      essentially for the aortic and subaortic bodies, leading, in this case, to an
      anterior and posterior localisation. We report a case of non-chromaffin non
      secreting aorticopulmonary paraganglioma, discovered fortuitously in a 64-year
      old man.

PMID- 14707930
TI  - [Paraneoplastic opsoclonus-myoclonus syndrome associated with small-cell lung
      cancer].
AB  - Opsoclonus-myoclonus syndrome was observed in a patient treated for small-cell
      lung cancer. Opsoclonus presented as anarchic involuntary eye movements
      associated with myoclonies of the limbs and trunk. Opsoclonus-myoclonus is
      exceptional and a specific expression among several paraneoplastic manifestations
      described in small-cell lung cancer. These manifestations develop late after
      diagnosis of cancer. Presence of anti-neuronal antibodies in the serum
      (inconstant) is a factor of very poor prognosis.

PMID- 14707931
TI  - [Fortuitously discovered lung nodules].
AB  - Pulmonary nodular amyloidosis is a rare entity. We report a new case where
      multiple nodules suggested, first, a neoplastic process. Clinical and
      radiological findings were non specific. Positive diagnosis was established at
      pathology.

PMID- 14707932
TI  - Predictive model of diagnosing probable cases of severe acute respiratory
      syndrome in febrile patients with exposure risk.
AB  - STUDY OBJECTIVE: Since the World Health Organization issued a global alert about
      severe acute respiratory syndrome (SARS) on March 12, 2003, the illness has
      become a major public health challenge worldwide. The objective of this study is
      to identify the clinical risk factors of SARS and to develop a scoring system for
      early diagnosis. METHODS: The detailed clinical data of all patients presenting
      to the emergency department (ED) with a temperature higher than 38.0 degrees C
      (100.3 degrees F), documented at home or at the ED, and risks of exposure to SARS
      within 14 days were assessed. The diagnosis of probable SARS was made according
      to the definition of the Centers for Disease Control and Prevention. Items with
      significant differences among symptoms, signs, and laboratory tests on
      presentation between SARS and non-SARS groups were determined and used to develop
      the scoring system. RESULTS: Seventy patients were enrolled and 8 were diagnosed
      as probably having SARS. None of the initially discharged patients or their
      relatives developed SARS. Compared with the non-SARS group, the SARS group was
      younger (33.9+/-15.9 years versus 44+/-9.8 years; P=.02), had a higher percentage
      of fever prolonged more than 5 days (87.5% versus 6.5%; P<.01), myalgia (75%
      versus 27.4%; P=.01), and diarrhea (50% versus 9.7%; P=.02); had less occurrence
      of cough before or during fever (0% versus 64.5%; P=.01); and had lower absolute
      lymphocyte (0.9+/-0.3x10(9)/L versus 1.5+/-1.1x10(9)/L; P<.01) and platelet
      counts (144.1+/-36.3x10(9)/L versus 211.6+/-78.8x10(9)/L; P=.02). A 4-item
      symptom score based on the presence of cough before or concomitant with fever,
      myalgia, diarrhea, and rhinorrhea or sore throat detects SARS with 100%
      sensitivity and 75.9% specificity; a 6-item clinical score based on lymphopenia
      (<1.0x10(9)/L), thrombocytopenia (<150x10(9)/L) and the 4 symptom items detects
      SARS with 100% sensitivity and 86.3% specificity. CONCLUSION: Certain symptoms
      and laboratory tests indicate higher risk of febrile probable SARS. In nonendemic
      areas, the febrile patients with recent contact with SARS or travel history to
      endemic areas could be screened for the probability of SARS by the use of
      clinical and symptom scores.

PMID- 14707933
TI  - An emergency department response to severe acute respiratory syndrome: a
      prototype response to bioterrorism.
AB  - STUDY OBJECTIVE: On March 13, 2003, Singapore physicians were alerted about an
      outbreak of atypical pneumonia that became known as severe acute respiratory
      syndrome (SARS). I describe the application of an emergency department (ED)
      disaster response plan to manage the SARS outbreak. METHODS: The ED implemented
      protection for staff, patients, and facility; infection control measures; and
      disaster-response workflow changes. The Ministry of Health, Singapore,
      centralized SARS cases in the hospital, and the ED became the national screening
      center. A screening questionnaire and a set of admission criteria were applied
      after assessment of clinical features and chest radiograph findings. RESULTS: For
      the duration of the outbreak that ended on May 31, 2003, the ED screened 11,461
      persons for SARS, of whom 1,386 (12.9%) were admitted to rule out SARS and 235
      (17%) were confirmed to have SARS. Among 10,075 persons discharged from the ED,
      there were 28 reattending patients who were admitted and diagnosed with SARS,
      giving an undertriage rate of 0.3% (95% confidence interval [CI] 0.1% to 0.4%).
      The sensitivity of an ED admission for SARS was 89.4% (95% CI 85.6% to 93.1%),
      and specificity was 89.7% (95% CI 89.2% to 90.3%). The positive predictive value
      was 17% (95% CI 15.7% to 18.4%), and the negative predictive value was 99.7% (95%
      CI 99.6% to 99.8%). No patient contracted SARS as a result of an ED visit. After
      full implementation of protective measures, 1 ED nurse with undiagnosed diabetes
      mellitus was treated for suspected SARS. CONCLUSION: Although the SARS outbreak
      was not a bioterrorism event, the ED disaster response was applicable in the
      outbreak's management. The use of a screening questionnaire and admission
      criteria enabled the ED to screen, treat, and safely discharge the majority of
      the patients.

PMID- 14707934
TI  - The limits of techne and episteme.

PMID- 14707935
TI  - Establishing a clinical decision rule of severe acute respiratory syndrome at the
      emergency department.
AB  - STUDY OBJECTIVE: In the absence of reliable rapid confirmatory tests during
      severe acute respiratory syndrome (SARS) endemics, we designed a 2-phase cohort
      study to establish a scoring system for SARS and to evaluate whether it could
      improve the sensitivity and specificity of the World Health Organization (WHO)
      criteria. METHODS: According to the clinical characteristics and initial
      laboratory findings of 175 suspected cases defined by the WHO criteria (20
      confirmed as cases of SARS) in 3 university teaching hospitals in Taipei between
      March 1 and April 20, 2003, the scoring system for SARS was designed by
      multivariate analysis and stepwise logistic regression as the simple arithmetic
      sum of point values assigned to 7 parameters. We thereafter applied the scoring
      system for SARS to the consecutive 232 patients (the validation group) who met
      the WHO criteria of suspected cases from April 21 to May 22, 2003. Final
      diagnosis of SARS was determined by the results of real-time polymerase chain
      reaction and paired serum. RESULTS: The scoring system for SARS was defined as
      radiographic findings of multilobar or bilateral infiltrates (3 points), sputum
      monocyte predominance (3 points), lymphocytopenia (2 points), history of exposure
      (1 point), lactate dehydrogenase more than 450 U/L (1 point), C-reactive protein
      more than 5.0 mg/dL (1 point), and activated partial prothrombin time more than
      40 seconds (1 point). Of the validation group, 60 patients (group A) were
      confirmed as having cases of SARS, and the other 172 (group B) patients tested
      negative for SARS. The total points of the scoring system for SARS at initial
      presentation were significantly higher in the SARS group (median 9; range 6 to
      11) than in the non-SARS group (median 4; range 3 to 7; P<.001). At the cutoff
      value of 6 points, the sensitivity and specificity of the scoring system for SARS
      in diagnosing SARS were 100% and 93%, respectively. The positive and negative
      predictive values of the scoring system for SARS were 83% and 100%, respectively.
      CONCLUSION: The scoring system for SARS can provide a rapid and reliable clinical
      decision to help emergency physicians detect cases of SARS more accurately in the
      endemic area.

PMID- 14707936
TI  - America's emergency care system and severe acute respiratory syndrome: are we
      ready?

PMID- 14707937
TI  - Sequential symptomatic analysis in probable severe acute respiratory syndrome
      cases.
AB  - STUDY OBJECTIVE: Previous reports on severe acute respiratory syndrome (SARS)
      described mainly its symptoms. However, the time sequence of symptom development
      was rarely discussed. The objective of this study is to chronologically document
      the time sequence of symptom development in probable SARS cases and compare that
      of the febrile non-SARS cases, thus providing valuable information for early
      recognition of the disease. METHODS: This prospective, descriptive, cohort study
      was conducted in an academic university hospital in Taipei, Taiwan, from March 14
      through May 12, 2003. Patients presenting to the emergency department (ED) with a
      temperature of at least 38.0 degrees C (> or =100.3 degrees F) and exposure
      history were evaluated with a structured protocol. Detailed time sequences of
      individual symptoms were recorded, and chest radiography and laboratory test
      results were obtained. Probable SARS cases were determined by the Center of
      Disease Control Taiwan. Children younger than 15 years and suspected SARS
      patients with negative polymerase chain reaction results were excluded from final
      analysis. RESULTS: Seventy-nine SARS and 220 non-SARS cases were analyzed. The
      major clinical symptoms of SARS patients on ED presentation were myalgia, loose
      stool or diarrhea, nonproductive cough or dyspnea, headache, and chills. Upper
      airway symptoms, including rhinorrhea and sore throat, were rarely seen in the
      SARS patients but were common in the non-SARS group. Characteristic symptom
      sequence, consisting of initial fever accompanied by diarrhea and myalgia and
      then progressive respiratory symptoms, was identified in 55 SARS patients (69.6%;
      95% confidence interval [CI] 0.60 to 0.80) but only 7 (3.2%; 95% CI 0.008 to
      0.05) non-SARS patients. Chest radiographic abnormality may precede lower
      respiratory tract symptoms in some SARS patients. CONCLUSION: During an outbreak
      period, recognition of possible SARS cases depends on the heightened awareness of
      its clinical presentation. Aside from travel and contact history, the time
      sequence of the accompanying symptoms of SARS should help first-line physicians
      screen SARS patients at an early stage.

PMID- 14707938
TI  - Validation of a novel severe acute respiratory syndrome scoring system.
AB  - STUDY OBJECTIVE: In a pilot study conducted during March 14 to April 2, 2003, 2
      severe acute respiratory syndrome (SARS) screening scores were developed for
      predicting SARS among febrile patients presenting to the emergency department
      (ED). The objective of this study is to validate these scoring systems with a
      different set of patients. METHODS: All adult patients with documented fever,
      measured at home or at the hospital, and presenting to the ED of National Taiwan
      University Hospital, a 2,400-bed tertiary care teaching hospital in northern
      Taiwan, were prospectively enrolled. Two previously developed SARS screening
      scores were applied to all patients. The final diagnosis of SARS was made by the
      Expert Committee of the Center for Disease Control Taiwan, Republic of China,
      according to the criteria of Centers for Disease Control and Prevention, Atlanta,
      GA. RESULTS: A total of 239 adult patients, including 117 men and 122 women, were
      enrolled. Eighty-two patients were finally diagnosed with SARS. Compared with the
      SARS patients in the derivation cohort, those in the validation cohort were older
      (44.5+/-15.9 versus 33.9+/-15.9 years), more likely to acquire the disease
      locally (76.8% versus 37.5%), and more likely to have cough before or during
      fever. For the non-SARS patients, cases in the validation cohort presented with
      less cough and coryza but more diarrhea. For the 4-item symptom score, the
      sensitivity reached 96.3% (95% confidence interval [CI] 89.7% to 98.7%) and the
      specificity 51.6% (95% CI 43.8% to 59.3%). For the 6-item clinical score, the
      sensitivity reached 92.6% (95% CI 84.8% to 96.6%) and the specificity 71.2% (95%
      CI 63.6% to 77.7%). When the clinical score was applied to patients with a
      positive symptom score, the combined sensitivity reached 90.2% (95% CI 82.0% to
      95.0%), and the combined specificity reached 80.1% (95% CI 73.2% to 85.6%).
      CONCLUSION: This prospective study validated the scoring system previously
      developed by using a different cohort. The scoring systems could be applied to
      settings where mass screening of SARS is needed during future outbreaks.

PMID- 14707939
TI  - Update on emerging infections:news from the Centers for Disease Control and
      Prevention. Methicillin-resistant Staphylococcus aureus infections among
      competitive sports participants--Colorado, Indiana, Pennsylvania, and Los Angeles
      County, 2000-2003.

PMID- 14707940
TI  - Alternating day emergency medicine and anesthesia resident responsibility for
      management of the trauma airway: a study of laryngoscopy performance and
      intubation success.
AB  - STUDY OBJECTIVE: We compare laryngoscopy performance and overall intubation
      success in trauma airways when primary airway management alternated between
      emergency medicine and anesthesia residents on an every-other-day basis. METHODS:
      Data on all trauma intubations during approximately 3 years were prospectively
      collected. Primary airway management was assigned to emergency department (ED)
      residents on even days and anesthesia residents on odd days. Emergency medicine
      residents intubated patients who arrived without notification or who needed
      immediate intubation before anesthesia arrived. The study was conducted in an
      inner-city, Level I trauma center with approximately 50,000 ED patients and 1,800
      major trauma cases a year. Main outcomes were success or failure at laryngoscopy
      and the number of laryngoscopy attempts needed for intubation. RESULTS: Six
      hundred fifty-eight trauma patients were intubated during the study period.
      Laryngoscopy was successful in 654 of 656 cases. Two (0.3%) patients underwent
      cricothyrotomy after failed laryngoscopy, and 2 (0.3%) patients had awake nasal
      intubation without laryngoscopy. The specific number of laryngoscopy attempts was
      unknown in 6 cases (3 from each service), resulting in 650 cases for laryngoscopy
      performance analysis. Overall, 87% of patients were intubated on first attempt,
      and 3 or more attempts occurred in 2.9% of patients. Laryngoscopy performance by
      service (broken down by 1, 2, and >or=3 attempts) was as follows: emergency
      medicine 86.4%, 11%, and 2.6% versus anesthesia 89.7%, 6.7%, and 3.6%. Analysis
      by service was done by using Wilcoxon Mann-Whitney testing (P=.225). CONCLUSION:
      There were no differences in laryngoscopy performance and intubation success in
      trauma airways managed on an every-other-day basis by emergency medicine versus
      anesthesia residents.

PMID- 14707941
TI  - Analysis of two-treatment, two-period crossover trials in emergency medicine.
AB  - In an AB/BA crossover trial, patients are randomly assigned to receive either
      treastment A in the first period followed by treatment B in the second period or
      treatment B in the first period followed by treatment A in the second period. The
      crossover trial allows for a within-patient comparison between treatments because
      each patient serves as his or her own control subject, removes the interpatient
      variability from the comparison between treatments, and can provide unbiased
      estimates for the differences between treatments. When applied inappropriately,
      crossover designs have serious problems that might adversely influence and
      invalidate their results. The primary concern is the residual carryover effect of
      a treatment in subsequent treatment periods. Rather than depending on a
      statistical procedure to eliminate the possibility of the presence of carryover
      effects, it is more important that the crossover design be used only in those
      situations in which the likelihood of a carryover effect is exceptionally small.
      Even though the AB/BA crossover trial appeals to the physician researcher, it is
      surprisingly difficult to take advantage of this design. The primary objective of
      this article is to introduce readers and trialists to some of the issues
      surrounding crossover trials. Researchers who use this design should explicitly
      examine the assumptions about crossover effects and the adequacy of the lead-in
      washout period and the between-period washout period and clearly indicate that
      the results of the study are conditional on the acceptance of those conditions.

PMID- 14707942
TI  - Outcome of patients with a final diagnosis of chest pain of undetermined origin
      admitted under the suspicion of acute coronary syndrome: a report from the
      Rochester Epidemiology Project.
AB  - STUDY OBJECTIVES: Patients presenting to the emergency department (ED) with chest
      pain after a recent negative inpatient evaluation for cardiac pathology represent
      a dilemma for the emergency physician. The purposes of this study were to assess
      the outcome of patients discharged with a diagnosis of chest pain of undetermined
      origin and to identify predisposing factors for further cardiac events. METHODS:
      The resources of the Rochester Epidemiology Project were used to identify all
      admitted ED patients with chest pain with suspected acute coronary syndrome who
      received a discharge diagnosis of chest pain of undetermined origin from 1985
      through 1992. Patient records were reviewed for the occurrence of adverse cardiac
      events and subsequent ED visits for recurrent chest pain within 12 months of
      discharge. Associations between patient characteristics and an adverse cardiac
      event were evaluated univariately and summarized by using odds ratios (ORs). Long
      term mortality was also determined. RESULTS: Among 1,973 admitted ED patients
      with chest pain, 230 were given a diagnosis of chest pain of undetermined origin.
      Ten (4.4%) of 230 patients experienced an adverse cardiac event. Factors
      significantly associated with an adverse cardiac event included an abnormal ECG
      on admission (OR 9.5; 95% confidence interval [CI] 2.0 to 45.8), preexisting
      diabetes mellitus (OR 7.1; 95% CI 1.8 to 27.2), and preexisting coronary artery
      disease (OR 28.4; 95% CI 3.5 to 229.0). Thirty-three (14%) patients returned to
      the ED within 12 months of discharge; 5 patients were given a diagnosis of a
      cardiac condition, and 5 were given a diagnosis of a gastrointestinal condition.
      In long-term follow-up, 46 patients died, with a mean time from hospital
      discharge to death of any cause of 6.1 years and an estimated 5-year survival of
      91.4%. CONCLUSION: Among patients discharged from the hospital with a diagnosis
      of chest pain of undetermined origin, those with an initial abnormal ECG,
      preexisting diabetes, or preexisting coronary artery disease are at higher risk
      of a subsequent adverse cardiac event. In the absence of such factors, cardiac
      outcome is excellent.

PMID- 14707943
TI  - Risk stratification of emergency department patients with chest pain: the need
      for standardized reporting guidelines.

PMID- 14707944
TI  - Lack of utility of telemetry monitoring for identification of cardiac death and
      life-threatening ventricular dysrhythmias in low-risk patients with chest pain.
AB  - STUDY OBJECTIVE: Low-risk patients with chest pain are often admitted to
      monitored beds; however, the use of telemetry beds in this cohort is not evidence
      based. We tested the hypothesis that monitoring admitted low-risk patients with
      chest pain for dysrhythmia is low yield (<1% detection of life-threatening
      dysrhythmias requiring treatment). METHODS: We conducted a prospective cohort
      study of emergency department (ED) patients with chest pain with a Goldman risk
      score of less than 8%, a normal initial creatine kinase-MB level, and a negative
      initial troponin I level admitted to non-ICU monitored beds. Investigators
      followed the hospital course daily. The main outcome was cardiovascular death and
      life-threatening ventricular dysrhythmia during telemetry. RESULTS: Of 3,681
      patients with chest pain who presented to the ED, 1,750 patients were admitted to
      non-ICU monitored beds. Of these, 1,029 patients had a Goldman risk score of less
      than 8%, a troponin I level of less than 0.3 ng/mL, and a creatine kinase-MB
      level of less than 5 ng/mL (accounting for 59% of all chest pain telemetry
      admissions). During hospitalization, there were no patients with sustained
      ventricular tachycardia/ventricular fibrillation requiring treatment on the
      telemetry service (0%; 95% confidence interval [CI] 0% to 0.3%). There were 2
      deaths: neither was cardiovascular in nature or preventable by monitoring
      (cardiovascular preventable death rate=0%; 95% CI 0.0% to 0.3%). CONCLUSION: The
      routine use of telemetry monitoring for low-risk patients with chest pain is of
      limited utility. Admission to nonmonitored beds might help alleviate ED crowding
      without increasing risk of adverse events caused by dysrhythmia in patients with
      a Goldman risk of less than 8%, an initial troponin I level of less than 0.3
      ng/mL, and a creatine kinase-MB level of less than 5 ng/mL.

PMID- 14707945
TI  - Emergency department crowding: emergency physicians and cardiac risk
      stratification as part of the solution.

PMID- 14707946
TI  - Nonsyndromic genetic predisposition to aortic dissection: a newly recognized,
      diagnosable, and preventable occurrence in families.
AB  - The major diseases affecting the aorta are aortic aneurysms and dissections, with
      patients with acute dissections often presenting in the emergency department
      (ED). Recent studies demonstrate a strong genetic predisposition to thoracic
      aortic aneurysms and dissections, independent of syndromes traditionally
      considered to predispose to aortic disease (such as Marfan syndrome).
      Nonsyndromic familial thoracic aortic aneurysms and dissections are inherited in
      families as an autosomal dominant disorder and a variable age of onset of the
      aortic disease. The case reported here illustrates the critical importance of
      obtaining a family history of thoracic aortic aneurysms and dissections, along
      with unexplained sudden death, when assessing an individual with chest pain in
      the ED, regardless of age and in the absence of a known genetic syndrome.

PMID- 14707947
TI  - Response to cardiac arrest and selected life-threatening medical emergencies: the
      medical emergency response plan for schools--a statement for healthcare
      providers, policymakers, school administrators, and community leaders.

PMID- 14707948
TI  - The effect of emergency department crowding on paramedic ambulance availability.
AB  - STUDY OBJECTIVE: We determine the effect of emergency department (ED) crowding on
      paramedic ambulance availability. METHODS: This was a prospective longitudinal
      study from April 2001 through March 2002 in Los Angeles, CA. All incidents in
      which a Los Angeles Fire Department ambulance was out of service for more than 15
      minutes while waiting to transfer a patient because of the lack of open ED beds
      were captured and analyzed. Data included the total time each ambulance was out
      of service and the hospital where paramedics were waiting for an open gurney.
      Analysis was performed to determine weekly and seasonal variations and
      preponderance at various hospitals. RESULTS: There were a total of 21,240
      incidents in which ambulances were out of service while waiting to transfer their
      patients to an open ED gurney, which accounted for 1 of every 8 transports. Of
      these, 8.4% were in excess of 1 hour. The median waiting time per incident was 27
      minutes, with an interquartile range of 20 to 40. There was a statistically
      significant difference in the monthly number of out-of-service incidents during
      the study (P<.0001), with the highest levels during the winter (January through
      March). CONCLUSION: ED crowding has resulted in delays for paramedics waiting to
      transfer patients. This decrease in ambulance availability may have a significant
      effect on emergency medical services systems' abilities to provide timely
      response.

PMID- 14707949
TI  - Nontraumatic out-of-hospital hypotension predicts inhospital mortality.
AB  - STUDY OBJECTIVE: Out-of-hospital hypotension may signify need for intensive
      resuscitation and rapid diagnosis on emergency department (ED) arrival. We
      hypothesized that nontraumatic out-of-hospital hypotension confers risk of
      inhospital mortality. METHODS: This was a multicenter study of ambulance
      transported, nontrauma, non-cardiopulmonary resuscitation patients conducted at 2
      venues: (1) a cross-sectional risk assessment study of high-priority medical
      transports at a US metropolitan county; and (2) a Canadian prospective
      multicenter cohort study of patients with respiratory distress. Data at both
      venues were extracted from prospectively recorded, standardized run sheets by
      either a physician or a paramedic. Data extraction and analysis at each venue
      were conducted independently. Exposures to hypotension were defined as age older
      than 17 years old, systolic blood pressure less than 100 mm Hg during transport,
      and 1 or more of 10 predefined symptoms of circulatory insufficiency.
      Nonexposures to hypotension had the same definition as exposures, except the
      systolic blood pressure had to be more than 100 mm Hg during the entire out-of
      hospital transport. The main outcome variable was inhospital mortality. RESULTS:
      At venue 1, of 3,128 transports, 395 (13%) exposures and 395 nonexposures were
      identified. Inhospital mortality of exposures was 26% versus 8% for nonexposures
      (adjusted odds ratio [OR] 4.6; 95% confidence interval [CI] 2.0 to 5.9). At venue
      2, of 7,679 transports, 532 exposures (7%) and 7,147 nonexposures were
      identified. Out-of-hospital exposure to hypotension conferred a mortality rate of
      32% versus 11% for nonexposures (OR 3.0; 95% CI 2.4 to 3.7), representing a
      sensitivity of 18% and a specificity of 95%. CONCLUSION: The inhospital mortality
      rate after out-of-hospital, nontraumatic hypotension is high and reproducible.
      Future research should focus on ED clinical protocols to ensure appropriate
      resuscitation and investigation of etiology of out-of-hospital hypotension.

PMID- 14707950
TI  - Emergency medical services. Residents' perspective.

PMID- 14707951
TI  - Performance of helical computed tomography without oral contrast for the
      detection of gastrointestinal injuries.
AB  - STUDY OBJECTIVE: We describe the performance of helical abdominal computed
      tomography (CT) scan without oral contrast for the detection of blunt
      gastrointestinal injuries. METHODS: We retrospectively reviewed the records of a
      consecutive series of patients who underwent helical abdominal CT scanning for
      evaluation of blunt intra-abdominal injury and were admitted to a Level I trauma
      center from May 1996 to September 2001. Abdominal CT scans were performed with
      intravenous contrast but without oral contrast. Patients were considered to have
      gastrointestinal injuries if an injury was identified to the gastrointestinal
      tract from the duodenum to the sigmoid colon or associated mesentery and
      considered to have major gastrointestinal injuries if gastrointestinal
      perforation, active mesenteric hemorrhage, or mesenteric devascularization
      occurred. All gastrointestinal injuries were confirmed by laparotomy, autopsy, or
      additional imaging studies. RESULTS: Six thousand fifty-two patients underwent
      abdominal CT scan (mean age 35.5 +/- 21.1 years), and 106 (1.8%) patients had
      gastrointestinal injuries identified by laparotomy, autopsy, or additional
      (nonabdominal CT) imaging studies. Abdominal CT scan result was abnormal in 91
      (86%; 95% confidence interval [CI] 78% to 92%) of the 106 patients with
      gastrointestinal injuries and revealed findings suggestive of gastrointestinal
      injury in 81 (76%; 95% CI 67% to 84%) patients. Abdominal CT scan demonstrated
      findings suggestive of gastrointestinal injury in 58 of 64 (91%; 95% CI 81% to
      96%) patients with major gastrointestinal injuries. Two hundred thirty-eight
      (4.0%) patients had findings suspicious for gastrointestinal injuries on
      abdominal CT scan, but gastrointestinal injury was never confirmed. CONCLUSION:
      Helical abdominal CT scan without oral contrast identified nearly three fourths
      of patients with blunt gastrointestinal injuries who were selected for abdominal
      CT scanning. Sensitivity of this diagnostic test improves in the subset of
      patients with major gastrointestinal injuries.

PMID- 14707952
TI  - Evidence-based emergency medicine. Blood pressure control in acute stroke.

PMID- 14707953
TI  - Evidence-based emergency medicine. Noninvasive positive pressure ventilation in
      acute chronic obstructive pulmonary disease.

PMID- 14707954
TI  - Maintenance of a large pericentric inversion generated by the hobo transposable
      element in a transgenic line of Drosophila melanogaster.
AB  - The impact of the hobo transposable element in the global reorganization of the
      Drosophila melanogaster genome has been investigated in transgenic lines
      generated by the injection of hobo elements into the Hikone strain, which lacked
      them previously. Extensive surveys of transgenic lines followed for 250
      generations have identified 13 inversions with hobo inserts at most breakpoints.
      One of these inversions is pericentric on chromosome 2. It has been maintained in
      the line where it was discovered and in several sublines at frequencies from 0.19
      to 0.45, generating stable chromosomal polymorphisms, similar to cosmopolitan
      paracentric inversions in natural populations. Individuals homozygous for this
      inversion were viable and fertile, allowing the creation of a new homozygous
      strain.

PMID- 14707955
TI  - Breast cancer--should ophthalmologists now be involved in screening?

PMID- 14707956
TI  - Comparison of optometry vs digital photography screening for diabetic retinopathy
      in a single district.
AB  - PURPOSE: To compare (a). the clinical effectiveness and (b). cost effectiveness
      of the two models in screening for diabetic retinopathy. METHODS: (a).
      Retrospective analysis of referral diagnoses of each screening model in their
      first respective years of operation and an audit of screen positive patients and
      a sample of screen negatives referred to the hospital eye service from both
      screening programmes. (b). Cost effectiveness study. PARTICIPANTS: (1). A total
      of 1643 patients screened in the community and in digital photography clinics;
      (2). 109 consecutive patients referred to the Diabetic Eye Clinic through the two
      existing models of diabetic retinopathy screening; (3). 55 screen negative
      patients from the optometry model; (4). 68 screen negative patients audited from
      the digital photography model. RESULTS: The compliance rate was 45% for optometry
      (O) vs 50% for the digital imaging system (I). Background retinopathy was
      recorded at screening in 22% (O) vs 17% (I) (P=0.03) and maculopathy in 3.8% (O)
      vs 1.7% (I) (P=0.02). Hospital referral rates were 3.8% (O) vs 4.2% (I)
      Sensitivity (75% for optometry, 80% for digital photography) and specificity (98%
      for optometry and digital photography) were similar in both models. The cost of
      screening each patient was pound 23.99 (O) vs pound 29.29 (I). The cost
      effectiveness was pound 832 (O) vs pound 853(I) in the first year. CONCLUSION:
      The imaging system was not always able to detect early retinopathy and
      maculopathy; it was equally specific in identifying sight-threatening disease.
      Cost effectiveness was poor in both models, in their first operational year
      largely as a result of poor compliance rates in the newly introduced screening
      programme. Cost effectiveness of the imaging model should further improve with
      falling costs of imaging systems. Until then, it is essential to continue any
      existing well-coordinated optometry model.

PMID- 14707957
TI  - Scanning laser polarimetry in patients with acute angle-closure glaucoma.
AB  - PURPOSE: To detect differences in retinal nerve fibre layer (RNFL) measurements
      between patients with acute angle-closure glaucoma (AACG) and normal subjects
      using scanning laser polarimetry. METHODS: This was a comparative cross-sectional
      study, where 32 eyes of 32 patients with AACG and 28 eyes of 28 normal subjects
      were imaged using scanning laser polarimetry (The Nerve Fibre Analyzer GDx, Laser
      Diagnostic Technology Inc., San Diego, CA, USA). The average RNFL thickness in
      four quadrants and various GDx parameters between the two groups were compared
      using Mann-Whitney tests with Bonferroni correction. RESULTS: There were no
      significant differences in RNFL measurements for the average thickness, ellipse
      average, inferior, superior, nasal, and temporal average values between the AACG
      eyes and normal eyes. There were significant differences in some GDx parameters,
      including superior/nasal ratio (P=0.036), superior ratio (P=0.01), the GDx number
      (P=0.003), inferior ratio (P<0.001), maximum modulation (P<0.001), and ellipse
      modulation (P<0.001). CONCLUSIONS: Various GDx parameters exhibit significant
      changes in patients following short-duration AACG episodes, making GDx RNFL
      measurements useful for the diagnosis and follow-up of AACG.

PMID- 14707958
TI  - Evaluation of the electrodiagnostic investigation of children using the Greenwich
      Grading System.
AB  - PURPOSE: To evaluate the contribution of electrodiagnostic testing (EDT) to the
      management of children in a paediatric ophthalmology service using the Greenwich
      Grading System (GGS). METHODS: A retrospective analysis was performed of the case
      notes of 105 of the 113 paediatric patients referred from the Strabismus and
      Paediatric Service at Moorfields Eye Hospital for electrophysiological testing
      over a 1-year period. The GGS was used to quantify the contribution of EDT to the
      diagnosis, overall investigation, and treatment of each patient. Patients were
      further subdivided into different diagnostic groups to allow comparison of the
      value of EDT in different conditions. RESULTS: EDT was found to be of value in
      91% of the children tested and was considered an essential investigation in 71%.
      EDT made a new diagnosis in 7% of patients, changed it in 5%, and confirmed or
      excluded a diagnosis in 79%. EDT made a useful contribution to the overall
      investigation of 89% of the patients and was considered the only test that could
      provide the required information in 71%. The results of EDT allowed reassurance
      and/or explanation with regard to the diagnosis, prognosis, and treatment in 91%
      of children. In one patient, treatment was changed as a result of EDT. The
      clinical outcome was not adversely affected in any patient. CONCLUSIONS: EDT was
      of value to the clinical management of most of the children reviewed, mainly by
      confirming or excluding a clinical diagnosis and allowing explanation and
      reassurance to children and parents. Electrodiagnostic information gave a new or
      changed diagnosis in 12% of the children.

PMID- 14707959
TI  - Assessment of functional nasolacrimal duct obstruction--a survey of
      ophthalmologists in the southwest.
AB  - The term 'functional nasolacrimal duct obstruction' describes patients with
      epiphora where the tear duct is partially or completely patent to syringing.
      Delayed tear drainage is demonstrated with a fluorescein dye disappearance test
      (FDDT) or lacrimal scintigraphy. A dacrocystogram is also frequently abnormal.
      Studies show that selected patients with epiphora because of functional
      nasolacrimal duct obstruction have an 80-90% success rate with open or endonasal
      dacryocystorhinostomy. To find out if such patients were being considered for
      surgery, we sent a questionnaire to all ophthalmologists in the southwest. Of the
      198 questionnaires, 163 were completed and returned (82%). In the assessment of
      epiphora, fewer than half those questioned (41%) regularly used an FDDT and only
      51% syringe patients themselves. Most did not use lacrimal scintigraphy or
      dacrocystography if the drainage system was patent on syringing. This survey
      shows that many patients with epiphora who are patent to syringing are being
      incompletely assessed, and hence not considered for dacrocystorhinostomy. We
      recommend that an FDDT is performed on all patients, syringing is carried out by
      experienced staff, and more radiological investigations are undertaken, so
      patients with a highly treatable cause of epiphora can be offered
      dacrocystorhinostomy.

PMID- 14707960
TI  - Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan) in
      children.
AB  - INTRODUCTION: Brimonidine 0.2% (Alphagan) is a topical alpha-2 agonist widely
      used as an antihypertensive. There have been occasional reports of systemic
      adverse effects in children including apparent central nervous system depression.
      There are few data available on the overall safety of brimonidine 0.2% in
      children. METHODS: Computerised pharmacy records were used to identify all
      children who had been prescribed brimonidine 0.2% in our eye department between
      August 1999 and June 2001, and their notes were reviewed. RESULTS: In all, 23
      patients were identified from pharmacy records and 22 sets of notes were
      recovered and reviewed. The mean age at commencement of treatment was 8 years
      (range 0-14 years). In all, 10 (46%) were treated in one eye and 12 (54%) in
      both. Brimonidine 0.2% was taken for a mean 14 months (range 1 day-75 months). A
      total of 14 (64%) patients were already taking a topical beta-blocker when
      brimonidine 0.2% was commenced and a further four (18%) were being treated with
      another topical hypotensive agent. Of the 22 patients, six (27%) had to stop
      brimonidine 0.2% because of adverse side effects (two because of local
      irritation/allergy, two because of tiredness, and two because of fainting
      attacks). DISCUSSION: Many topical hypotensive agents are not licensed for use in
      children and few safety data are available. In this study, 18% of children had
      systemic adverse effects sufficient to necessitate stopping the drug. It is
      possible that educational impairment may have passed unnoticed in others. Larger
      studies are required to investigate this further.

PMID- 14707961
TI  - Association of binocular lower visual field impairment, impaired simultaneous
      perception, disordered visually guided motion and inaccurate saccades in children
      with cerebral visual dysfunction-a retrospective observational study.
AB  - The principal pathways serving higher visual function comprise the dorsal stream
      and the ventral stream. The dorsal stream runs between the occipital lobes and
      the parietal lobes and subserves the ability to process the whole visual scene
      and carry out visually guided movement. The ventral stream runs between the
      occipital lobes and temporal lobe tissue and primarily subserves visual
      recognition and memory. These tissues are susceptible to dysfunction in children
      with brain damage. We report a series of 40 children in whom damage to the brain
      has led to a common symptom complex affecting vision. Lower visual field loss was
      frequently elicited. This was associated with impaired ability to make accurate
      visually guided movement (particularly of the lower limbs) accompanied by
      impaired simultaneous perception, and in some cases, with inaccurate saccades and
      in others, impaired perception of movement. These features are consistent with
      parietal/dorsal stream dysfunction. Difficulty recognising faces and problems
      with route finding (which are ventral stream functions) were also present in a
      number of the children. These visual difficulties can be manifest in the presence
      of normal visual acuity. Recognition of these problems leads to understanding of
      the child's visual difficulties and facilitates adaptation of curriculum delivery
      at school.

PMID- 14707962
TI  - Modular phakoemulsification training adapted for a left-handed trainee.
AB  - BACKGROUND: The increasing demand for high-volume, high-quality cataract surgery
      creates additional challenges for surgeons providing phakoemulsification
      training. We describe the modular training programme used by the Worcester Eye
      Department for inexperienced trainees and the adaptation of this programme to the
      needs of a left-handed trainee. METHODS: The intraoperative complications of a
      left-handed trainees' first 161 cases are reported. RESULTS: In this series,
      there was one case of vitreous loss (0.62%) and one case of posterior capsular
      tear (0.62%). Two cases developed stable anterior capsular tears (1.24%) and two
      cases required a single suture to ensure wound stability. CONCLUSION: We
      demonstrate a safe, effective and flexible method of phakoemulsification
      training.

PMID- 14707963
TI  - Screening for ophthalmic involvement in asymptomatic patients with metastatic
      breast carcinoma.
AB  - BACKGROUND: Breast carcinoma metastasises to the eye more frequently than is
      clinically recognised. The incidence is perhaps not appreciated, either because
      of the more common involvement and consequences of spread to major organs (such
      as lung, liver, or bone) or because a number of eye lesions are small and
      asymptomatic. Over a 6-month period, all patients with locally advanced or
      metastatic breast cancer were screened for ocular involvement and as a result
      management recommendations made. MATERIALS AND METHODS: Between January 2001 and
      June 2001, 68 patients with known locally advanced or metastatic breast carcinoma
      were referred for a screening ophthalmic examination. The aim of the study was to
      assess the frequency of asymptomatic ocular metastases by breast carcinoma in
      visually asymptomatic patients. The recognition and early treatment of both
      ocular metastases and ocular manifestations of metastatic breast carcinoma are
      important in maximising the quality of life in this group of palliative patients.
      These patients were all referred and recruited from the Beatson Oncology Centre
      and Breast Unit at the Western Infirmary, Glasgow by the oncologist (ANH).
      Examination included visual acuity assessment, slit-lamp examination, tonometry,
      and indirect ophthalmoscopy. RESULTS: The median time from diagnosis of breast
      carcinoma to ophthalmic screening was 5 years (range 6 months-23 years). No
      patient had any evidence of choroidal metastases on ophthalmic examination. Four
      patients (5.8%) had ophthalmic manifestations of metastatic breast carcinoma and
      a further two had ocular complications of treatment. One patient had a
      restrictive motility problem from a metastatic deposit to her lateral rectus
      muscle and another had corneal punctate epitheliopathy secondary to a seventh
      nerve palsy. A further patient had coarse nystagmus from cerebellar metastases
      and the final patient of the four had a Horner's syndrome from metastases in the
      neck. In addition, two patients had symptomatic dry eyes whose onset coincided
      with commencement of chemotherapy. CONCLUSION: Ophthalmic manifestations of
      metastatic breast carcinoma occurred in 5.8% of asymptomatic patients. Orbital
      metastases were documented in one patient. No case of choroidal metastases was
      observed in this group with advanced or metastatic disease. Therefore, patients
      do not need to be routinely screened particularly for choroidal metastases.

PMID- 14707964
TI  - Metoprolol responding uveitis.
AB  - BACKGROUND: Noninfectious uveitis is usually managed by topical and systemic
      corticosteroids and in refractory cases by immunosuppressive drugs. OBJECTIVE: To
      describe a patient with noninfectious anterior and posterior uveitis, refractory
      to corticosteroids, and immunosuppressive therapy, which responded to systemic
      metoprolol. PATIENT AND METHODS: A 49-year-old patient was treated for 3 years
      with topical and systemic corticosteroids and systemic cyclosporin A for a
      bilateral anterior and posterior uveitis of unknown origin. The treatment did not
      result in resolution of the uveitis. A bilateral uveitic glaucoma developed and
      necessitated neodymium : YAG laser iridotomies and antiglaucoma medications. A
      systemic beta-blocker, metoprolol tartrate 50 mg b.i.d., was administered for
      palpitations because of idiopatic paroxysmal supraventricular tachycardia and
      short ventricular tachycardia. RESULTS: Following administration of metoprolol
      tartrate, the bilateral uveitis resolved. The corticosteroids and the cyclosporin
      A were withdrawn after 6 weeks without any recurrence. A trial to discontinue
      metoprolol after 6 months resulted in flare-up of the disease and only following
      its readministration the inflammation resolved. The patient is currently under
      metoprolol for a year without flare-ups. CONCLUSIONS: The use of metoprolol
      tartrate in this patient resulted in resolution of bilateral noninfectious
      uveitis. This is the first report of non-antiinfectious, antiinflammatory, or
      immunosuppressive drug effective for uveitis. It is possible that a subgroup of
      resistant uveitis may respond to drugs other than the traditional drugs, such as
      metoprolol, and that other forms of uveitis of unidentified origin exist.

PMID- 14707965
TI  - Unintentional inversion of corneal buttons during penetrating keratoplasty:
      clinico-pathological report of two cases.
AB  - AIM: This report describes the clinico-pathological features of unintentionally
      inverted corneal buttons in two patients. METHODS: A clinico-pathological report.
      RESULTS: Two patients who underwent repeat keratoplasty for failed grafts were
      found to have inverted corneal buttons on histopathological examination. A
      detailed description of the pathological features of the inverse keratoplasty and
      the clinical outcome after repeat keratoplasty is presented. CONCLUSION:
      Inadvertent inverse keratoplasty should be considered as a rare cause of corneal
      graft failure. The serious complication of anterior chamber epithelialization
      seems to be unlikely and the prognosis following repeat penetrating keratoplasty
      appears to be very good.

PMID- 14707966
TI  - Improved survival rates in sebaceous carcinoma of the eyelid.
AB  - PURPOSE: To review the clinicopathological features, management, and survival
      rates for patients with sebaceous gland carcinoma of the eyelid, and to analyse
      the reasons for improved survival. METHODS: In the west of Scotland between 1975
      and 2001, 32 cases were identified through the pathology index for sebaceous
      carcinoma. Pathology specimens were reviewed in all cases. The clinical data were
      obtained from hospital records and the database provided by the Regional Cancer
      Registry. RESULTS: A total of 22 female and 10 male patients were identified.
      Follow-up ranged from 6 months to 15 years, median of 4.8 years. Primary
      treatment involved excisional techniques in 27 cases, exenteration in two cases,
      enucleation in two cases, and two cases required adjuvant radiotherapy.
      Intraepithelial spread and masquerade presentations delayed the diagnosis. Poorly
      differentiated tumours were associated with an unfavourable outcome. Three
      patients developed local tumour recurrence and one metastatic disease. In all, 10
      patients died from nontumour-related causes and one died from metastatic
      sebaceous carcinoma. The overall tumour mortality rate in the west of Scotland
      was 3%. CONCLUSIONS: From this study, patients in the west of Scotland have a
      better prognosis than is indicated in the literature. Astute clinical suspicion
      and accurate histopathological diagnosis, together with radical and aggressive
      surgical approaches were key factors.

PMID- 14707967
TI  - Brown deposits in the optic of foldable intraocular lenses in patients with
      uveitis.
AB  - PURPOSE: To report a new finding of brown deposits scattered in the substance of
      the optic of foldable intraocular lenses (IOL) following phakoemulsification in
      patients with uveitis. METHODS: Consecutive uveitis patients (54 patients, 71
      eyes) who had undergone phakoemulsification with a foldable posterior chamber IOL
      between March 1996 and November 2000 were studied. A variety of biomaterials from
      seven different manufacturers had been implanted. One masked observer using slit
      lamp biomicroscopy assessed deposits in the substance of the optic of the IOL.
      RESULTS: Brown deposits were detected in the substance of the optic of 25/71
      (35%) IOLs with 18/22 (82%) of AcrySof MA60BM IOLs being affected. Using logistic
      regression analysis, the AcrySof MA60BM IOL was significantly associated with the
      presence of deposits (adjusted odds ratio=38.5, 95% CI 6.9-200, P<0.001). Using
      multiple regression analysis, there was a significant association between the
      severity of deposits and the use of the AcrySof MA60BM IOL (P=0.005). Compared
      with other foldable IOLs implanted, the AcrySof MA60BM IOL was 38.5 times more
      likely to develop intra-IOL deposits. There was no association with those eyes
      that had undergone increased intraocular manipulations. The deposits did not
      appear to affect visual acuity. CONCLUSIONS: To our knowledge the finding of
      brown intra-IOL deposits has not previously been described. These deposits are
      more frequent in the AcrySof MA60BM implant than the other foldable implants
      studied. They share some similarities with glistenings, but their exact nature
      remains unknown.

PMID- 14707968
TI  - Clinical outcome following cataract surgery in very elderly patients.
AB  - PURPOSE: The number of very elderly patients waiting for cataract surgery is
      predicted to increase. The aim of our study was to determine the clinical outcome
      following cataract surgery in this age group. METHODS: In this retrospective
      study, patients aged 96 years and above, who underwent cataract surgery between
      June 1993 and January 2001, were identified. Clinical data were retrieved from
      their medical records. Living patients were further invited for clinical
      examination. RESULTS: In all, 34 eyes of 21 patients (20 females) were
      identified. Six patients were deceased. In total, 30/34 eyes had
      phacoemulsification and four had extracapsular extraction. Preoperative vision
      was <or=6/36 in 24/34 eyes (70.59%) and <or=CF in 16/34 eyes (47.06%).
      Postoperative vision was >or=6/60 in 25/34 eyes (73.53%), >or=6/18 in 21/34 eyes
      (61.76%), and >or=6/9 in 10/34 eyes (29.41%). Visual acuity improved in 24/34
      eyes (70.59%) and remained the same in 6/34 eyes. Complications included anterior
      capsule tear (three), zonular dialysis with vitreous loss (one), posterior
      capsule rupture with vitreous loss (one), incarceration of iris to paracentesis
      wound (two), postoperative uveitis (two), and posterior capsular opacification
      (19). In all, 7/34 eyes had undergone YAG capsulotomy. CONCLUSION: Surgeons
      should not be deterred from offering cataract surgery to the very elderly as
      successful visual rehabilitation is the norm. A further prospective multicentre
      study is required to confirm the benefits and assess the risks of cataract
      surgery in this age group.

PMID- 14707969
TI  - National biometry audit.
AB  - PURPOSE: To determine compliance with the Royal College of Ophthalmologists'
      (RCOphth) biometry guidelines. METHOD: A structured telephone questionnaire of
      individuals who perform biometry in all eye departments in the United Kingdom
      (UK). RESULTS: A biometrist was interviewed in 107 of the UK's 178 eye
      departments. Nurses alone run the biometry service in 58% of departments,
      orthoptists alone in 13%, junior doctors alone in 6%, optometrists alone in 3%,
      and a combination of staff in 20%. Of the staff interviewed, 37% had been on
      external biometry training courses. One intraocular lens (IOL) calculation
      formula was used for all eyes in 61% of departments with 17% using the obsolete
      SRK II formula, 36% of departments used two or more formulae and only 4% adhered
      to the RCOphth guidelines to use Hoffer Q in eyes with axial lengths <22.0 mm, an
      average of all three formulae in eyes between 22.0 and 24.5 mm, Holladay in eyes
      between 24.6 and 26.0 mm, and SRK/T in eyes >26.0 mm. Audit of refractive results
      was claimed by 71% of units but in only 17 (16%) did the biometrist know the
      percentage of eyes with a prediction error <or=1 D. CONCLUSION: This study
      demonstrates poor awareness and/or implementation of the RCOphth biometry
      guidelines and indicates that audits are either not highlighting poor results or
      are not resulting in a change in practice. The guidelines should be updated to
      emphasise the importance of customising A constants and to set benchmark
      standards for prediction error.

PMID- 14707970
TI  - Effect of nicotine exposure during gestation on neonatal rat crystalline lenses.
AB  - PURPOSE: To assess histologically the influence of maternal nicotine exposure
      during gestation in vivo on crystalline lenses in neonatal rats using different
      dosages of the test compound simulating the range of low, moderate, and heavy
      smokers in humans. METHODS: Experimentally naive, adult female Wistar-albino rats
      (200-250 g) were mated with adult male rats over 2 days for copulation in the
      proportion of two females for every male animal. After confirming pregnancy with
      vaginal smear method, 40 gravid rats (dams) were then randomly assigned into four
      equal groups (three experimental and one control; n=10 in each). Groups 1, 2, and
      3 experimental dams were treated with intraperitoneal (i.p.) (-)-nicotine
      tartrate at doses of 0.5, 1, and 2 mg/kg body weight/day, respectively, during
      pregnancy from gestational days 9 through 21. Group 4 control dams were given
      i.p. saline solution daily for the same period. After normal delivery, the eyes
      were removed at postnatal day 1 or day 30 for macroscopic and histopathologic
      investigation of the lenses. RESULTS: Control and group 1 litters had normal
      anterior lens capsules with a single layer of anterior cuboidal epithelial cells,
      regularly orientated cortical and nuclear lens fibres, and a clear posterior lens
      capsule with no lining epithelial cells behind the equator. On the other hand,
      some lenses in groups 2 and 3 litters had mature or immature cataract
      macroscopically at postnatal 30th day. Histopathologic findings suggesting
      cataractogenesis included cortical lens fibre cell swelling and liquefaction,
      prominent epithelial cells lining the posterior lens capsule behind the equator,
      and the retention of lens nuclei into the deeper and central area. Moreover, some
      lenses were immature developmentally, indicating arrested lenticular
      embryogenesis at vesicle stage. CONCLUSIONS: Nicotine exposure during pregnancy
      has teratogenic and cataractogenic effects on developing crystalline lenses in
      neonatal rats both macroscopically and histopathologically. If appropriate dose
      of nicotine can be identified, nicotine-induced cataract formation may possibly
      be used as a new experimental cataract model in animal studies. Therefore, future
      studies are needed in this respect. Eye (2004) 18, 67-73.
      doi:10.1038/sj.eye.6700511

PMID- 14707971
TI  - A rare and unusual congenital arteriovenous communication of the retina.

PMID- 14707972
TI  - A new cause for retinal haemorrhage and disc oedema in child abuse.

PMID- 14707973
TI  - Pleomorphic adenoma of the lacrimal gland in a teenager, a case report.

PMID- 14707974
TI  - Double jeopardy; brain abscess and subdural empyema presenting with painful
      enlargement of orbital varices in a patient with known encephalocele.

PMID- 14707975
TI  - Vertical augmented transposition surgery.

PMID- 14707976
TI  - A non-idiopathic case of polypoidal choroidal vasculopathy.

PMID- 14707977
TI  - Spontaneous regression of optic disc neovascularization in Takayasu arteritis.

PMID- 14707978
TI  - Marcus Gunn syndrome.

PMID- 14707979
TI  - Pseudo-Terson's syndrome: bilateral simultaneous rhegmatogenous retinal
      detachment.

PMID- 14707980
TI  - Extrascleral extension of choroidal malignant melanoma following transpupillary
      thermotherapy.

PMID- 14707981
TI  - Tadpole pupil.

PMID- 14707982
TI  - Eyelid metastases indicating neuroendocrine carcinoma of unknown origin.

PMID- 14707983
TI  - Bilateral Ulnar nerve palsies: an unusual complication of posturing after macular
      hole surgery.

PMID- 14707984
TI  - Metastatic endogenous endophthalmitis secondary to Staphylococcus aureus
      iliopsoas abscess.

PMID- 14707985
TI  - Dermatochalasis: a potential pitfall in botulinum rejuvenation.

PMID- 14707986
TI  - Dehiscence of radial keratotomy incision during phacoemulsification.

PMID- 14707987
TI  - Diplopia following intravenous administration of pamidronate.

PMID- 14707988
TI  - Horner's syndrome following attempted internal jugular venous cannulation.

PMID- 14707989
TI  - Primary position upbeat nystagmus associated with amitriptyline use.

PMID- 14707990
TI  - Diabetic maculopathy and lipid-lowering therapy.

PMID- 14707991
TI  - Lipids, diabetic maculopathy, and cardiovascular risk.

PMID- 14707992
TI  - Contact lenses in the management of high anisometropic amblyopia.

PMID- 14707994
TI  - Optic neuritis: a rare manifestation of nasopharyngeal carcinoma.

PMID- 14707995
TI  - What do your authors do?

PMID- 14707996
TI  - 'Hyperacute' unilateral anterior uveitis and secondary glaucoma following
      streptokinase infusion.

PMID- 14707997
TI  - Re: confusion between similarly named eye drops.

PMID- 14708000
TI  - Differential regulation of synaptic vesicle proteins by antidepressant drugs.
AB  - Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release
      and neural plasticity, and have been implicated in the pathophysiology of
      psychiatric disorders such as depression. Antidepressant drugs not only alter the
      level of neurotransmitters, but also modulate de novo gene transcription and
      synthesis of proteins involved in neural plasticity. In order to investigate the
      effects of antidepressant compounds on SVP-mRNA levels, the expressions of
      synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ
      hybridization in rats which had been treated with desipramine, fluoxetine,
      tranylcypromine, or saline. The results demonstrate that chronic treatment with
      fluoxetine and tranylcypromine leads to an increased expression of synaptophysin,
      but decreased expression of synaptotagmin and VAMP in the hippocampus and
      cerebral cortex. Additionally, synapsin I-mRNA levels in the hippocampus and
      cerebral cortex are significantly reduced in tranylcypromine-treated animals.
      This identifies SVP genes as target genes of antidepressant treatment.

PMID- 14708001
TI  - Genesis of dendritic spines: insights from ultrastructural and imaging studies.

PMID- 14708002
TI  - The mammillary bodies: two memory systems in one?

PMID- 14708003
TI  - Structural plasticity and memory.

PMID- 14708004
TI  - The neurobiology of nicotine addiction: bridging the gap from molecules to
      behaviour.

PMID- 14708005
TI  - The relevance of behavioural measures for functional-imaging studies of
      cognition.

PMID- 14708006
TI  - Microtubules and the shape of plants to come.
AB  - Plants control the direction of cell expansion as a way of shaping growth. Since
      their discovery in plants 40 years ago, microtubules have been suspected of
      forming a template that helps to regulate the direction of growth. The detailed
      mechanism, however, has been elusive, especially as plants lack a microtubule
      organizing centre. Developmental mutants are now beginning to show how
      microtubules are organized and how this affects plant morphology.

PMID- 14708007
TI  - The GGA proteins: adaptors on the move.
AB  - The GGA proteins are a family of ubiquitously expressed, Arf-dependent clathrin
      adaptors that mediate the sorting of mannose-6-phosphate receptors between the
      trans-Golgi network and endosomes. Recent studies have elucidated the biochemical
      and structural bases for the interaction of the GGA proteins with many binding
      partners, and have shed light on the molecular and cellular mechanisms by which
      the GGA proteins participate in protein sorting.

PMID- 14708008
TI  - Regulation of the c-Abl and Bcr-Abl tyrosine kinases.
AB  - The prototypic non-receptor tyrosine kinase c-Abl is implicated in various
      cellular processes. Its oncogenic counterpart, the Bcr-Abl fusion protein, causes
      certain human leukaemias. Recent insights into the structure and regulation of
      the c-Abl and Bcr-Abl tyrosine kinases have changed the way we look at these
      enzymes.

PMID- 14708009
TI  - From polyploidy to aneuploidy, genome instability and cancer.
AB  - Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological
      properties of polyploid cells are not well understood. During evolution,
      polyploidy is thought to be an important mechanism that contributes to
      speciation. Polyploid, usually non-dividing, cells are formed during development
      in otherwise diploid organisms. A growing amount of evidence indicates that
      polyploid cells also arise during a variety of pathological conditions. Genetic
      instability in these cells might provide a route to aneuploidy and thereby
      contribute to the development of cancer.

PMID- 14708010
TI  - Tubby proteins: the plot thickens.
AB  - The tubby mouse, which shows late-onset obesity and neurosensory deficits, arises
      from a mutation in the Tub gene. Tub shares homology with the genes for tubby
      like proteins Tulp1, Tulp2 and Tulp3. Ablation of Tub, Tulp1 or Tulp3 causes
      disease phenotypes that are indicative of their importance in nervous-system
      function and development. Despite this importance, the biochemical functions of
      tubby-like proteins are only now beginning to be understood. At present, data
      indicate that tubby-like proteins might function as heterotrimeric-G-protein
      responsive intracellular signalling factors, although an array of data also
      implicates them in other processes.

PMID- 14708011
TI  - Ageing, repetitive genomes and DNA damage.
AB  - The mitochondrial production of reactive oxygen species is inversely proportional
      to longevity in animals. A key question now is, which molecules, among those that
      are oxidized, affect the lifespan of the organism most significantly?

PMID- 14708012
TI  - Systematic genome-wide screens of gene function.

PMID- 14708013
TI  - A genomics-based approach to biodefence preparedness.

PMID- 14708014
TI  - Design of gene circuits: lessons from bacteria.

PMID- 14708015
TI  - The X chromosome in population genetics.

PMID- 14708016
TI  - The causes and consequences of HIV evolution.

PMID- 14708017
TI  - The age of model organisms.

PMID- 14708018
TI  - The IKK NF-kappa B system: a treasure trove for drug development.

PMID- 14708019
TI  - Steroid-hormone rapid actions, membrane receptors and a conformational ensemble
      model.

PMID- 14708020
TI  - Crystal structures of drugs: advances in determination, prediction and
      engineering.

PMID- 14708021
TI  - Fluorescent probes for proteolysis: tools for drug discovery.

PMID- 14708022
TI  - Embryonic stem cells in drug discovery.

PMID- 14708023
TI  - Challenges of implementing pharmacogenetics in the critical care environment.

PMID- 14708024
TI  - Cytokines in cancer pathogenesis and cancer therapy.

PMID- 14708025
TI  - Paraneoplastic neurological degenerations: keys to tumour immunity.

PMID- 14708026
TI  - Peroxisome-proliferator-activated receptors and cancers: complex stories.

PMID- 14708027
TI  - Tumour-educated macrophages promote tumour progression and metastasis.

PMID- 14708028
TI  - Impact of race/ethnicity on molecular pathways in human cancer.

PMID- 14708030
TI  - Molecular abnormalities of the hippocampus in severe psychiatric illness:
      postmortem findings from the Stanley Neuropathology Consortium.
AB  - Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples
      from the Stanley Neuropathology Consortium. From these data sets, 224 total
      measures were available from the various subdivisions of the hippocampus. An
      integrative analysis of these measures was performed using a multivariate,
      nonparametric analysis of variance (ANOVA). ANOVA with correction for multiple
      comparisons indicated that parvalbumin-containing cells in CA2 were reduced in
      schizophrenia and bipolar disorder. In addition, reelin protein in the molecular
      layer of the dentate gyrus was decreased in schizophrenia, bipolar disorder, and
      depression at the trend level of statistical significance (P=0.065). These
      results strongly suggest a dysfunction of inhibitory GABA-ergic interneurons in
      severe mental illness. Without correction for multiple comparisons, 31 measures
      were abnormal in at least one disease, whereas 11 measures would be expected to
      appear abnormal by chance. Abnormal molecules included measures of synaptic
      density or neuronal plasticity (reelin, SNAP-25, BDNF, Complexin I and II), as
      well as parvalbumin, tyrosine receptor kinase A, glucocorticoid receptors,
      glutamate NR1 receptor subunits, serotonin 5HT2(A) and 5HT1(B) receptors, and
      dopamine D(5) receptors.

PMID- 14708029
TI  - Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic
      population.
AB  - The role of the serotonin transporter (5-HTT) in the development of
      neuropsychiatric disorders has been widely investigated. Two polymorphisms, an
      insertion/deletion in the promoter region and a 12 repeat allele in a variable
      nucleotide tandem repeat (VNTR) in intron 2, drive higher expression of the 5-HTT
      gene. Four studies have shown nominally significant excess transmission of
      alleles of the 5-HTT gene in autism, while three studies have reported no excess
      transmission. This present study investigates the role of 5-HTT in the
      genetically homogenous Irish population. In all, 84 families were genotyped for
      five polymorphisms (three SNPs, a VNTR and an in/del). The analysis of allele
      transmissions using the transmission disequilibrium test (TDT) was undertaken and
      indicated preferential transmission of the short promoter allele (TDT P
      value=0.0334). Linkage disequilibrium between markers was calculated and
      haplotypes were assessed for excess transmission and odds ratios (ORs) to
      affected children. A number of haplotypes, especially those involving and
      surrounding SNP10, showed evidence of association. The ORs ranged from 1.2 to
      2.4. The most significant haplotype associated with transmission to affected
      probands was the SNP10-VNTR-SNP18 haplotype (chi(2)=7.3023, P=0.0069, odds
      ratio=1.8). This haplotype included the 12 repeat allele of the VNTR, which is
      associated with increased expression and may play a subtle role in the early
      development of the brain in affected probands.

PMID- 14708031
TI  - Protein profiling of human postmortem brain using 2-dimensional fluorescence
      difference gel electrophoresis (2-D DIGE).
AB  - Two-dimensional gel electrophoresis (2-D GE) is a key tool for comparative
      proteomics research. With its ability to separate complex protein mixtures with
      high resolution, 2-D GE is a technique commonly employed for protein profiling
      studies. Significant improvements have been made in 2-D GE technology with the
      development of two-dimensional fluorescence difference gel electrophoresis (2-D
      DIGE), where proteins are first labelled with one of three spectrally resolvable
      fluorescent cyanine dyes before being separated over first and second dimensions
      according to their charge and size, respectively. When used in conjunction with
      automated analysis packages, this multiplexing approach can accurately and
      reproducibly quantify protein expression for control and experimental groups.
      Differentially expressed proteins can be subsequently identified by mass
      spectrometric methods. Here, we describe the successful application and
      optimisation of 2-D DIGE technology for human postmortem brain studies. This
      technology, especially when coupled with other functional genomics approaches,
      such as transcriptomics and metabolomics studies, will enhance our current
      understanding of human disease and lead to new therapeutic and diagnostic
      possibilities.

PMID- 14708032
TI  - Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when
      compared with the minimal model.
AB  - OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled
      intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses
      with surrogate measures of insulin sensitivity and resistance and to compare
      features of the metabolic syndrome between Caucasians and Indian Asians living in
      the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK
      Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si
      of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent
      minimal model analysis. The concentrations of insulin, glucose and nonesterified
      fatty acids (NEFA) were analysed in fasting plasma and used to calculate
      surrogate measure of insulin sensitivity (quantitative insulin sensitivity check
      index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin
      resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index,
      fasting insulin, insulin-to-glucose ratio). Plasma concentrations of
      triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and
      low density cholesterol, (LDL-C) were also measured in the fasted state.
      Anthropometric measurements were conducted to determine body-fat distribution.
      RESULTS: Correlation analysis identified the strongest relationship between Si
      and the revised QUICKI (r=0.67; P=0.000). Significant associations were also
      observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009),
      FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a
      higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive
      (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI
      demonstrated a statistically strong relationship with the minimal model. However,
      it was unable to differentiate between insulin-sensitive and -resistant groups in
      this study. Future larger studies in population groups with varying degrees of
      insulin sensitivity are recommended to investigate the general applicability of
      the revised QUICKI surrogate technique.

PMID- 14708033
TI  - Physical disability and muscular strength in relation to obesity and different
      body composition indexes in a sample of healthy elderly women.
AB  - OBJECTIVES: The aim of the present study was to test the association between
      muscular strength, functional limitations, body composition measurements and
      indexes of sarcopenia in a sample of community-dwelling, elderly women at the
      high end of the functional spectrum. DESIGN: Cross-sectional. SUBJECTS: In all,
      167 women aged 67-78 y were selected from the general population in central
      Verona. A group of 120 premenopausal healthy women aged 20-50 y represented the
      young reference group. MEASUREMENTS: Body weight, height, body mass index (BMI)
      and the presence of acute and chronic conditions were evaluated in each subject.
      Body composition was measured by dual-energy X-ray absorptiometry (DXA). Physical
      functioning was assessed using a modified version of the Activities of Daily
      Living Scale. Dominant leg isometric strength was measured with a Spark Handheld
      Dynamometer. RESULTS: Elderly women with BMI higher than 30 kg/m(2) and in the
      highest quintile of body fat percent showed a significantly higher prevalence of
      functional limitation. In our population study, about 40% of sarcopenic elderly
      women and 50% of elderly women with high body fat and normal muscle mass were
      functionally limited. The prevalence of functional limitation significantly
      increased in subjects with class II sarcopenia, defined according to the skeletal
      muscle mass index (SMI=skeletal muscle mass/body mass x 100). In logistic
      regression models, after adjusting for age and different chronic health
      conditions, subjects with BMI higher than 30 kg/m(2), in the highest quintile of
      body fat, or with high body fat and normal muscle mass or class II sarcopenia
      according to SMI, had a 3-4 times increased risk of functional limitations.
      Finally, isometric leg strength was significantly lower in subjects in the lowest
      quintile of relative muscle mass and in sarcopenic and sarcopenic obese women.
      CONCLUSIONS: High body fat and high BMI values were associated with a greater
      probability of functional limitation in a population of elderly women at the high
      end of the functional spectrum. Among the different indexes of sarcopenia used in
      this study, only SMI predicted functional impairment and disability. Isometric
      leg strength was significantly lower in subjects with sarcopenia and sarcopenic
      obesity.

PMID- 14708034
TI  - Race affects insulin and GLP-1 secretion and response to a long-acting
      somatostatin analogue in obese adults.
AB  - OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin
      LAR Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely
      obese adults, (2) whether octreotide suppression of insulin secretion occurs by
      both a direct beta-cell effect and through mediating a glucagon-like peptide 1
      (GLP-1) response, and (3) whether differences in GLP-1 concentrations could
      explain racial differences in insulin concentrations. DESIGN: Prospective, open
      label trial using a pre-post test design. SETTING: Single university, clinical
      research center. SUBJECTS: In all, 42 healthy, severely obese Caucasian and
      African-American (AA) adults (93% female, 64% Caucasian, age=37.8+/-1.2 y,
      weight=123+/-4.2 kg, BMI=44.5+/-1 kg/m(2)), recruited through physician referral
      and newspaper ads, participated in the study. INTERVENTIONS: Indices of beta-cell
      activity, insulin and GLP-1 response before and during a 75-gm oral glucose
      tolerance test were determined before and after 24 weeks of octreotide-LAR.
      RESULTS: AA exhibited higher beta-cell activity, and insulin and GLP-1
      concentrations than Caucasians. Octreotide-LAR suppressed the insulin and GLP-1
      levels in both groups.

PMID- 14708035
TI  - Additive effect of the mutations in the beta3-adrenoceptor gene and UCP3 gene
      promoter on body fat distribution and glycemic control after weight reduction in
      overweight subjects with CAD or metabolic syndrome.
AB  - OBJECTIVE: To analyze the effects of the mutations in the beta3-adrenoceptor
      (beta3-AR) gene and/or uncoupling protein3 (UCP3) gene promoter on body fat
      distribution and glycemic control after mild weight reduction in overweight-obese
      subjects with coronary artery disease (CAD) or metabolic syndrome. DESIGN:
      Clinical intervention study of the -300 kcal/day mild weight reduction program
      for 12 weeks. SUBJECTS: A total of 224 overweight-obese subjects with CAD or
      metabolic disorder, subdivided into the following four categories: (1) wild type
      (TT-CC, n=73); (2) only UCP3 promoter variant (TT-CT/TT, n=90); (3) only beta3-AR
      variant (TA/AA-CC, n=29); (4) both variants (TA/AA-CT/TT, n=32). MEASUREMENT:
      Body mass index (BMI), blood pressure, calorie intakes, body fat distribution,
      serum glucose, insulin, free fatty acids, C-peptide and lipids before and after
      weight reduction. RESULTS: After 12 weeks, all subjects lost approximately 5% of
      their initial body weight. Despite similar weight reduction, the highest
      decreases in abdominal adipose tissue at both L1 and L4 levels were observed in
      the 'wild-type' group (P<0.001) and the second highest in 'only UPC3 promoter
      variant' group (P<0.001). On the other hand, both variant-carriers had the
      smallest reduction only in visceral fat area at the L4 level. All subjects except
      both variant-carriers showed significant reductions in the fasting levels of
      glucose and FFA. The response areas of glucose (P<0.01) and insulin (P<0.05) were
      reduced largest in the 'wild-type' group and second largest in the 'UCP3 promoter
      variant' group. CONCLUSION: All the four groups showed similar weight reduction
      after -300 kcal/d for 12 weeks. However, the beneficial effects on body fat
      distribution and glycemic control were greatest in the 'wild-type' group and
      smallest in 'both variants' group. In addition, these effects were less
      beneficial in carriers with beta3-AR gene variant than with UCP3 gene promoter
      variant.

PMID- 14708040
TI  - Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences
      in calcitropic hormones between Greenlanders and Danes.
AB  - We studied the influence of age, gender, latitude, season, diet and ethnicity on
      plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D
      binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46
      Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45
      Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders
      (group C), and 43 Danes (Group D) living in Denmark (55 degrees N) on a
      westernized fare. Blood specimens were drawn both summer and winter. Vitamin D
      insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups
      during summer (23-74%) and winter (42-81%). Compared to groups A and D, vitamin D
      insufficiency was significantly more frequent in groups B and C. In all groups,
      summer levels of 25 OHD were above winter levels. Multiple regression analysis
      revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had
      higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite
      relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D
      levels were influenced by age, season (summer > winter), and diet (a traditional
      Inuit diet>westernized diet). Ethnic differences exist between Greenlanders and
      Danes. Our results suggest that Greenlanders may have an inherent lower "set
      point" for calcium-regulated PTH release or an enhanced renal 1,25(OH)(2)D
      production. In addition to ethnicity, age, season, and diet were important
      determinants of vitamin D status. Changes from a traditional to a westernized
      fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D
      supplementation should be considered.

PMID- 14708042
TI  - Bone mineral density referral for dual-energy X-ray absorptiometry using
      quantitative ultrasound as a prescreening tool in postmenopausal women from the
      general population: a cost-effectiveness analysis.
AB  - The aim of our study was to assess, from the perspective of the National Health
      Services in Spain, the cost-effectiveness of quantitative ultrasound (QUS) as a
      prescreen referral method for bone mineral density (BMD) assessment by dual
      energy X-ray absorptiometry (DXA) in postmenopausal women of the general
      population. Using femoral neck DXA and heel QUS. We evaluated 267 consecutive
      postmenopausal women 65 years and older and attending primary care physician
      offices for any medical reason. Subjects were classified as osteoporotic or
      nonosteoporotic (normal or osteopenic) using the WHO definition for DXA.
      Effectiveness was assessed in terms of the sensitivity and specificity of the
      referral decisions based on the QUS measurement. Local costs were estimated from
      health services and actual resource used. Cost-effectiveness was evaluated in
      terms of the expected cost per true positive osteoporotic case detected. Baseline
      prevalence of osteoporosis evaluated by DXA was 55.8%. The sensitivity and
      specificity for the diagnosis of osteoporosis by QUS using the optimal cutoff
      thresholds for the estimated heel BMD T-score were 97% and 94%, respectively. The
      average cost per osteoporotic case detected based on DXA measurement alone was
      23.85 euros. The average cost per osteoporotic case detected using QUS as a
      prescreen was 22.00 euros. The incremental cost-effectiveness of DXA versus QUS
      was 114.00 euros per true positive case detected. Our results suggest that
      screening for osteoporosis with QUS while applying strict cufoff values in
      postmenopausal women of the general population is not substantially more cost
      effective than DXA alone for the diagnosis of osteoporosis. However, the
      screening strategy with QUS may be an option in those circumstances where the
      diagnosis of osteoporosis is deficient because of the difficulty in accessing DXA
      equipment.

PMID- 14708043
TI  - Laparoscopic needle catheter jejunostomy: modification of the technique and
      outcome results.
AB  - BACKGROUND: We describe a modification of the technique for laparoscopic
      jejunostomy in patients with stenosis of the upper gastrointestinal tract and
      assess the patients outcomes with this enteral access. METHODS: In a
      retrospective study of 80 patients, we evaluated the outcome of a modified
      technique for the laparoscopic placement of a jejunostomy catheter into the
      proximal jejunum. Standard laparoscopy equipment and ready-to-use jejunostomy
      catheters were used. After the creation of a pneumoperitoneum, the proximal
      jejunal loop was fixed to the parietal peritoneum. The jejunum was then punctured
      with a split needle, and the catheter (9F) was pushed into the jejunum. Finally,
      the catheter was secured with an additional purse-string suture. The external
      fixation was performed with nonabsorbable sutures. Enteral nutritional support
      with a polymeric enteral diet was initiated after fluoroscopic control on the
      first postoperative day at a rate of 20 ml/h. The flow rate was increased
      progressively until the nutritional goal of 60-80 ml/h was reached on the 3rd or
      4th postoperative day. RESULTS: In all patients (n = 80), the placement site of
      the catheter was correct, and all patients were able to receive enteral nutrition
      on the 1st postoperative day. There were no intraoperative complications. The
      mean operating time was 51 min. Two patients developed a localized infection at
      the catheter site; one patient developed an abscess; and three patients had
      catheter obstructions. CONCLUSIONS: Patients in need of intermediate or long-term
      enteral nutrition may benefit from laparoscopic catheter jejunostomy. The
      technique described is safe, effective, and less invasive than alternative
      techniques of laparoscopic jejunostomy.

PMID- 14708044
TI  - Postoperative wound surveillance is costly.

PMID- 14708045
TI  - The incidence of inflammatory change in abdominal aortic aneurysm (AAA).

PMID- 14708046
TI  - Total mesorectal excision for rectal cancer: the truth lies underneath.
AB  - The surgical technique itself has emerged as a crucial factor for local
      recurrence since the popularization of total mesorectal excision for the
      treatment of rectal cancer. This procedure is associated with lower local
      recurrence rates after "curative" surgery compared to traditional dissection of
      the rectum. The aim is to remove an intact mesorectal envelope from the
      promontorium down to the pelvic floor by sharp dissection with tumor-free margins
      and without causing injury to the pelvic nerves. However, the description of
      total mesorectal excision has been confusing. Moreover, the implication that
      total excision of all the perirectal fat contained within the perirectal fascia
      en bloc in all patients with rectal cancer can minimize local recurrence remains
      contentious. Therefore a critical appraisal of the procedure is required.
      Nonrandomized clinical studies have shown that total mesorectal excision reduces
      the local recurrence rate and increases disease-free survival in patients with
      adenocarcinoma of the middle and distal third of the rectum. Circumferential
      resection margins of 2 mm or more are associated with a lower local recurrence
      rate. Additional benefits in local control can be obtained with neoadjuvant
      treatment. Thus the modern treatment of rectal cancer combining total mesorectal
      excision with neoadjuvant chemoradiation results in excellent local tumor
      control. However, it is achieved at the cost of significant functional sequelae
      and impaired quality of life. The development of therapeutic alternatives that
      can achieve similar rates of local and distant tumor control without the
      mortality, morbidity, and functional consequences of radical surgery is a major
      challenge for colorectal surgeons.

PMID- 14708047
TI  - Clinical and molecular biologic characteristics of early-onset versus late-onset
      colorectal carcinoma in Filipinos.
AB  - A case-control study of Filipino patients who underwent surgical resection for
      colorectal cancer (CRC) during a 1-year period was undertaken. Thirty-five
      patients under age 40 years were identified. Paraffin blocks of these and 35
      randomly selected patients over age 40 underwent histologic and
      immunohistochemical evaluation. Markers chosen for evaluation included the
      apoptosis-associated gene products (p53 and bcl-2), a tumor proliferation
      activity-related factor (Ki-67), and the markers (MLH1 and MSH2) of DNA
      microsatellite instability (MSI). Results were correlated with age and the stage
      and location of the tumor. The average age of the early-onset group was 30.7
      years compared to the late-onset group at 67.0 years; and the male/female ratio
      was equivalent. The younger patients had a significantly higher Dukes' stage, the
      tumors were more poorly differentiated, and they were more frequently of the
      mucinous and signet ring cell histopathologic type. Expression of p53 was higher
      in the younger patients ( p < 0.001) and was independent of the degree of
      differentiation or the stage of the tumor. No differences of expression were
      noted for the other markers measured. The increased frequency of CRC in Filipino
      patients less than 40 years of age offers a unique opportunity to gain a better
      understanding of carcinogenesis, which might be exploited during diagnosis and
      management. The differences noted between the early- and late-onset CRC are
      provocative and provide an impetus for increased screening in Filipinos.

PMID- 14708048
TI  - Impact of intraoperative parathyroid hormone monitoring on the prediction of
      multiglandular parathyroid disease.
AB  - Optimal interpretation of the results of intraoperative parathyroid hormone
      (IOPTH) monitoring during neck exploration for primary hyperparathyroidism (pHPT)
      is still controversial. The reliability of the "50% rule" in multiglandular
      disease (MGD) is often disputed, mostly because of competing pathophysiologic
      paradigms. The aim of this study was to ascertain and corroborate the ability of
      IOPTH monitoring to detect MGD in a practice, combining conventional and
      alternative parathyroidectomy techniques. This is a retrospective single
      institution analysis of 69 consecutive patients undergoing cervical exploration
      for pHPT by various approaches. The IOPTH measurements were performed after
      induction of anesthesia but prior to skin incision and 10 minutes after excision
      of the first visualized enlarged parathyroid gland. In this series, 55 patients
      (80%) had single adenomas, and 14 patients (20%) had MGD. In 8 of the 14 patients
      with MGD, IOPTH levels were obtained sequentially after removal of every enlarged
      gland. Of these 8 patients, 6 (75%) had a false-positive decrease (decrease below
      50% of baseline value in presence of another enlarged gland) failing to predict
      the presence of a second enlarged gland. In 2 cases IOPTH monitoring provided a
      true-negative result, correctly predicting MGD. If MGD is defined by gross
      morphologic criteria, IOPTH monitoring fails to predict the presence of MGD
      reliably. However, if MGD is defined by functional criteria, the course of these
      patients does not seem significantly affected. The importance of these findings
      must be further investigated, especially with regard to the outcome of minimally
      invasive parathyroid procedures.

PMID- 14708049
TI  - Surgical mortality score: risk management tool for auditing surgical performance.
AB  - Existing methods of risk adjustment in surgical audit are complex and costly. The
      present study aimed to develop a simple risk stratification score for mortality
      and a robust audit tool using the existing resources of the hospital Patient
      Administration System (PAS) database. This was an observational study for all
      patients undergoing surgical procedures over a two-year period, at a London
      university hospital. Logistic regression analysis was used to determine
      predictive factors of in-hospital mortality, the study outcome. Odds ratios were
      used as weights in the derivation of a simple risk-stratification model-the
      Surgical Mortality Score (SMS). Observed-to-expected mortality risk ratios were
      calculated for application of the SMS model in surgical audit. There were 11,089
      eligible cases, under five surgical specialties (maxillofacial, orthopedic, renal
      transplant/dialysis, general, and neurosurgery). Incomplete data were 3.7% of the
      total, with no evidence of systematic underreporting. The SMS model was well
      calibrated [Hosmer-Lemeshow C-statistic: development set (3.432, p = 0.33),
      validation set (6.359, p = 0.10) with a high discriminant ability (ROC areas:
      development set [0.837, S.E.=0.013] validation set [0.816, S.E. = 0.016]).
      Subgroup analyses confirmed that the model can be used by the individual
      specialties for both elective and emergency cases. The SMS is an accurate risk-
      stratification model derived from existing database resources. It is simple to
      apply as a risk-management, screening tool to detect aberrations from expected
      surgical outcomes and to assist in surgical audit.

PMID- 14708050
TI  - Bloodless liver resection using the monopolar floating ball plus ligasure
      diathermy: preliminary results of 16 liver resections.
AB  - Blood loss during liver transection and ischemia-reperfusion injury associated
      with hepatic inflow occlusion are significant drawbacks during liver surgery.
      Sixteen patients underwent liver resection using the Monopolar Floating Ball (FB)
      plus LigaSure (LS) diathermy without occlusion of the hepatoduodenal ligament
      (group FB-LS). The liver parenchyma was precoagulated using the FB, and the
      uncovered tiny vessels were sealed using LS. Surgical outcomes were
      retrospectively compared with 16 well matched patients who underwent liver
      resection using the conventional clamp crushing method with Pringle's maneuver
      (group CC). The amount of blood loss during liver transection was significantly
      less in group FB-LS than in group CC [200 ml (0-990 ml) vs. 480 ml (120-1800 ml);
      p = 0.006]. The median time it took to complete the liver transection was
      significantly longer in group FB-LS than in group CC [144 minutes (43-335
      minutes) vs. 58 minutes (18-94 minutes); p < 0.0001]. Hepatic inflow occlusion
      was temporally used in five patients in group FB-LS to achieve hemostasis in
      hepatic venous tributaries for 6, 10, 19, 26, and 61 minutes, respectively. Using
      these two electronic devices allows liver resection to be safely performed, with
      the advantage of minimal blood loss and a reduced inflow occlusion period
      compared to the conventional method. The major disadvantage may be a slower
      transection speed. A prospective randomized trial is needed to clarify the
      clinical benefits of liver resections performed using this novel technique.

PMID- 14708051
TI  - Serum monocyte chemoattractant protein-1 in patients with postoperative
      infectious complications from gastrointestinal surgery for cancer.
AB  - We examined the kinetics of serum monocyte chemoattractant protein-1 (MCP-1)
      perioperatively and clarified its significance regarding the development of
      infectious complications. We studied 94 patients who underwent gastrointestinal
      surgery for gastric or colorectal cancer at Mie University Hospital from 1996 to
      2000. Serum concentrations of MCP-1 and interleukin-6 (IL-6) were measured
      perioperatively. The number of circulating lymphocytes and neutrophils were
      counted to assess the apoptotic rate of neutrophils. Patients were divided into
      two groups at the median preoperative MCP-1 level obtained from 40 gender- and
      age-matched healthy volunteers. The rate of developing infectious complications
      was significantly higher and tumor size was significantly larger in the low MCP-1
      group than in the high MCP-1 group. The increasing IL-6 ratio
      (postoperative/preoperative IL-6 level) in the low MCP-1 group was about twofold
      greater than that in the high MCP-1 group. The neutrophil level calculated for
      the low MCP-1 group was significantly higher than that in the high MCP-1 group on
      postoperative day 3. We concluded that a decreased level of serum MCP-1 reflected
      tumor-related immunosuppression. Low MCP-1 levels were associated with an
      exaggerated postoperative IL-6 response and delayed neutrophil apoptosis, which
      affected the incidence of postoperative infectious complications developing in
      patients with gastrointestinal malignancies.

PMID- 14708052
TI  - Presentation and prognosis of gastric cancer in patients aged 80 years and older.
AB  - The aim of this study was to analyze the characteristics of the presentation and
      prognosis of patients aged >/= 80 who were diagnosed with gastric adenocarcinoma.
      We have used a retrospective cohort study of 2334 patients diagnosed between 1975
      and 1993 in northwestern Spain, 263 (11.3%)of whom were >/= 80 years of age. No
      differences were observed with respect to patients of a younger age at diagnosis
      regarding the site of the tumor, extension of the disease, or Lauren's histologic
      type. However, fewer resections with curative intent were performed in the older
      group (49.1% vs. 30.1%; p < 0.0001). Among those operated on with curative or
      palliative intent, at the end of the first month the survival probability was 0.9
      and the 0.95% confidence interval (CI 95%) was 0.93-0.97 for patients < 80 years
      of age and 0.93 (CI 95% 0.89-0.98) for the older group ( p = 0.19). At the end of
      5 years of follow-up these probabilities were 0.29 (CI 95% 0.27-0.31) and 0.18
      (CI 95% 0.14-0.23), respectively ( p < 0.0001). If we consider only those
      patients undergoing curative resection, the survival probability for the two
      groups ( p = 0.4) was not statistically different. In conclusion, although the
      two groups showed similar characteristics at presentation, patients >/= 80 years
      of age underwent surgery with curative intent less frequently and their general
      prognosis was worse. Our data support the idea that curative surgery should not
      be ruled out exclusively for reasons of age.

PMID- 14708053
TI  - Appraisal of surgical treatment for pT2 gallbladder carcinomas.
AB  - This retrospective study was designed to appraise the surgical procedures for pT2
      gallbladder (GB) carcinomas. Twenty patients with pT2 GB carcinomas underwent
      surgical resection. Hepatectomy of segments 4b and 5 was performed in 19
      patients, and an extended right hepatic lobectomy was performed in 1. The
      extrahepatic bile duct was preserved in 8 patients in whom the disease was
      limited to the GB fundus and/or body. Regional lymphadenectomy was performed in
      18 patients. A separate radical second operation was performed in 8 patients
      after cholecystectomy. Final pathological staging was stage IB in 15 patients,
      IIB in 4, and IV in 1. Overall 5-year survival rate in those 20 patients was 77%
      without operative deaths. The 5-year survival rate in 5 patients with nodal
      metastasis and in 8 patients without extrahepatic biliary resection was 80% and
      100%, respectively. A separate radical second operation in 8 patients yielded 75%
      survival after 5 years. Perineural invasion as a prognostic determinant was
      closely associated with tumor extending to the neck or the cystic duct. Partial
      hepatectomy, usually with extrahepatic biliary resection and regional
      lymphadenectomy, was appropriate as a standard radical operation for pT2 GB
      carcinoma, but preservation of extrahepatic bile duct is advocated for disease
      limited to the GB fundus and/or body. Radical second operation enhanced the
      chance for cure in patients with pT2 GB carcinoma.

PMID- 14708054
TI  - Special wound healing methods used in ancient egypt and the mythological
      background.
AB  - The Egyptian civilisation is one of the oldest in history and was renowned for
      its scientific and artistic achievements, and medicine was no exception. The
      ancient Egyptians were masters in applying and arranging bandages, and they
      recognized the cardinal signs of infection and inflammation. Egyptian drug
      therapy can be regarded as having evolved from a system rooted in magic and
      empirical observation. To illustrate how the Egyptian wound healing methods
      provided a major stimulus for the development of surgery, we conducted a
      literature search.

PMID- 14708056
TI  - Relaparotomy for suspected intraperitoneal sepsis after abdominal surgery.
AB  - Relaparotomy may be beneficial in patients developing intraperitoneal sepsis
      after abdominal procedures. We determined whether joint clinical assessment by
      intensivist and surgeon (clinician assessment) identified patients with
      surgically correctable intraperitoneal sepsis. We also assessed the effect of
      patient age and sex, disease presentation and severity, interval to relaparotomy,
      and the number of relaparotomies on survival after relaparotomy. Data on
      clinical, laboratory, and radiologic abnormalities prior to relaparotomy,
      relaparotomy findings, and in-hospital survival were prospectively collected on a
      general hospital intensive care unit (ICU) database between January 1997 and
      January 2002. Altogether, 65 of 1482 (4.4%) patients admitted to the ICU after
      abdominal surgery underwent relaparotomy at a median of 5 days after the initial
      procedure. There was an 83% probability of identifying surgically treatable
      sepsis and 43% in-hospital mortality. Abdominal imaging contributed accurate
      information in 50% of cases where clinician assessment was uncertain. Patient age
      and multiorgan failure prior to relaparotomy-but not urgency of initial
      laparotomy or the acute physiology and chronic health evaluation (APACHE II)
      score prior to relaparotomy, interval to relaparotomy, or number of
      relaparotomies-affected the outcome. Clinician assessment after abdominal surgery
      had a high probability of predicting intraperitoneal sepsis at relaparotomy. The
      43% mortality after relaparotomy was unlikely to be greater than with
      nonoperative treatment of intraabdominal sepsis, but the 78% mortality after
      relaparotomy in patients older than 75 years of age raised doubts about this
      approach in the elderly. The identification of intraperitoneal sepsis and
      performance of relaparotomy earlier after the initial abdominal surgery might
      reduce the high rate (60%) of multiorgan failure prior to relaparotomy and
      improve survival after it.

PMID- 14708057
TI  - Health-related quality of life after restorative proctocolectomy for ulcerative
      colitis: long-term results.
AB  - Restorative proctocolectomy (RPC) is the favorite operation for ulcerative
      colitis, but it may influence health-related quality of life (HRQL). Our aims
      were to determine the long-term HRQL of patients and its modifications after a 5
      year follow-up and to identify any risk factor for a worse outcome. We enrolled
      36 patients submitted to RPC (mean follow-up 8.4 +/- 4.7 years), 36 ulcerative
      colitis (UC) patients, and 36 healthy subjects. We used a previously validated
      questionnaire that explored bowel symptoms, systemic symptoms, emotional
      function, and social function. A series of 17 patients had completed the same
      questionnaire 5 years earlier. Clinical and surgical factors were investigated.
      Statistical analysis was performed with Student's t-test, Wilcoxon matched-pairs
      test, and Fisher's exact test. The scores of the RPC patients were significantly
      better than those of moderate or severe UC patients, similar to those with
      remission/mild UC, and higher than those of the controls. The scores of patients
      interviewed 5 years earlier did not change in the present study, except for
      patients during the first postoperative year, in whom the scores were now
      significantly better. The analysis of RPC patients in subgroups showed that the
      use of drugs, high stool frequency, pouchitis, pelvic complications, and younger
      age at UC diagnosis worsened the HRQL outcome. We concluded that RPC patients,
      after a long-term follow-up, had an HRQL similar to that of the remission/mild UC
      patients. Recently operated patients improved their quality of life mainly
      because of improved emotional function, and patients who had been operated on for
      a longer time maintained their HRQL. HRQL is influenced by drugs, stool
      frequency, pouchitis, postoperative pelvic complications, and age at diagnosis.

PMID- 14708058
TI  - The subject of preoperative biliary decompression.

PMID- 14708059
TI  - Treatment of uncomplicated hydatid cyst of the liver by closed marsupialization
      and fibrin glue obliteration.
AB  - Treatment of hepatic echinococcosis remains a surgical problem not only in
      endemic countries. Between January 1983 and December 1999 a total of 29 patients
      underwent surgical treatment for hepatic hydatidosis at the Department of General
      Surgery at the University Hospital of Granada. The diagnosis was based on
      clinical criteria, serology, and imaging techniques. There were 16 male and 12
      female patients (ages 7-67 and 30-74 years, respectively). Concomitant
      extrahepatic complications were found in seven patients. Among them, five had
      secondary parasitic cysts in the peritoneal cavity. In one case an intrathoracic
      rupture was found, and one patient suffered an intraabdominal rupture with
      anaphylactic shock. The right lobe was affected in 62% (18 patients). Hepatic
      cysts were multiple in 4 cases and calcified in 13. Conservative surgical
      procedures were performed in 23 patients (closed marsupialization with fibrin
      glue obliteration in 17 and drainage-marsupialization in 6), and radical surgical
      procedures were undertaken in 6 (pericystectomy in 5 and hemihepatectomy in 1).
      One patient underwent an explorative laparotomy with intraabdominal lavage
      followed by pericystectomy after primary resuscitation due to anaphylactic shock.
      The mean period of hospitalization was 15.9 days, and there were no serious
      postoperative complications or fatal outcomes. The perioperative morbidity rate
      was 2.5%. One patient suffered a recurrence of the disease following drainage
      marsupialization after an interval of 5 years. Our results indicate that the
      closed marsupialization technique is a safe, sparing method for treating
      uncomplicated hepatic hydatidosis. The results were also compared to those of a
      former study reported by our group in which the experience of another 19 years
      was presented.

PMID- 14708060
TI  - Changing patterns of gallstone disease in Korea.
AB  - The aim of this study was to investigate the epidemiologic characteristics and
      changing patterns of gallstone disease in Korea over a recent 20-year period. A
      total of 4020 gallstone patients who had undergone surgery at Seoul National
      University Hospital during 1981-2000 were analyzed according to periods: period I
      (1981-1985: 831 cases); period II (1986-1990: 888 cases); period III (1991-1995:
      1040 cases); period IV (1996-2000: 1261 cases). The literature from 13 institutes
      in Korea reporting a total of 13,101 gallstone cases were reviewed to elucidate
      the nationwide trend. The number of gallstone cases gradually increased. A female
      predominance was not noted (F/M = 1.17-1.37) as is seen in Western countries. The
      patients with common bile duct (CBD) stones were older than those with
      gallbladder (GB) stones or intrahepatic duct (IHD) stones. Over time, the
      relative proportion of those with a GB stone increased, plateauing (80-85%)
      during the 1990s; that of patients with CBD stones decreased (34% --> 19%); and
      that of those with IHD stones remained unchanged (11-15%). Over the entire
      period, the rural pattern of gallstone formation (low number of GB stones, high
      numbers of CBD and IHD stones) has become similar to the urban pattern. The body
      mass index (BMI) of the GB stone group was above average, as were the BMIs of the
      CBD stone and IHD stone groups. Throughout the literature review, this same
      changing pattern of the relative proportion of gallstone disease was confirmed.
      Thus the pattern of gallstone disease in Korea has become similar to that seen in
      Western countries except for a high prevalence of hepatolithiasis.

PMID- 14708065
TI  - Decision tree algorithm for detection of spatial processes in landscape
      transformation.
AB  - The conversion of landscapes by human activities results in widespread changes in
      landscape spatial structure. Regardless of the type of land conversion, there
      appears to be a limited number of common spatial configurations that result from
      such land transformation processes. Some of these configurations are considered
      optimal or more desirable than others. Based on pattern geometry, we define ten
      processes responsible for pattern change: aggregation, attrition, creation,
      deformation, dissection, enlargement, fragmentation, perforation, shift, and
      shrinkage. A novelty in this contribution is the inclusion of transformation
      processes causing expansion of the land cover of interest. Consequently, we
      propose a decision tree algorithm that enables detection of these processes,
      based on three parameters that have to be determined before and after the
      transformation of the landscape: area, perimeter length, and number of patches of
      the focal landscape class. As an example, the decision tree algorithm is applied
      to determine the transformation processes of three divergent land cover change
      scenarios: deciduous woodland degradation in Cadiz Township (Wisconsin, USA) 1831
      1950, canopy gap formation in a terra firme rain forest at the Tiputini
      Biodiversity Station (Amazonian Ecuador) 1997-1998, and forest regrowth in
      Petersham Township (Massachusetts, USA) 1830-1985. The examples signal the
      importance of the temporal resolution of the data, since long-term pattern
      conversions can be subdivided in stadia in which particular pattern components
      are altered by specific transformation processes.

PMID- 14708066
TI  - Forest cover change, physiography, local economy, and institutions in a mountain
      watershed in Nepal.
AB  - This study assessed changes in forest cover in a mountain watershed in central
      Nepal between 1976 and 2000 by comparing classified satellite images coupled by
      GIS analyses, and examined the association of forest change with major
      physiographic, economic, and local forest governance parameters. The results
      showed an increase in forested area (forest plus shrublands) by 7.6% during 1976
      2000. Forest dynamism (changes including improvement, deterioration, gain, and
      loss) was highest in low-elevation, south-facing and less-steep slopes that were
      closer to roads. Proportionately the highest net improvement and gain to forested
      area also took place in those locations. Forest degradation occurred at twice the
      rate of improvement in high elevation areas (> 2300 m). Forests located in urban
      and semiurban areas (i.e., a market-oriented economy) experienced a
      proportionately higher amount of net improvement and gain than forests in rural
      areas (i.e., a subsistence economy). Among the three governance arrangements,
      proportionately the highest net improvement and gain took place in semigovernment
      forests (forested area legally under the forest department but with de facto
      control and claim of ownership by local communities and/or municipality) followed
      by formalized community forests (including leasehold). Government forests, which
      were mostly found in the southern high mountains and had virtually open access,
      remained relatively stable during the study period. Over 50% of the watershed
      forests have not come under community-based management despite favorable policy
      and more than two decades of government intervention with continuous donor
      support. The findings indicate that the present "one size fits all" approach of
      community forest handover policy in Nepal needs rethinking to accommodate
      biophysical and socioeconomic variations across the country.

PMID- 14708067
TI  - Nerve growth factor plasma levels and ventricular repolarization in Rett
      syndrome.
AB  - Rett syndrome is a severe neurological developmental disorder. In this syndrome,
      the high incidence of sudden death is correlated with an alteration of
      ventricular repolarization. The purpose of this study was to evaluate plasmatic
      levels of nerve growth factor (NGF) in Rett patients with prolonged corrected QT
      (QTc) interval in comparison with those of Rett patients with normal QTc. We
      observed 23 female Rett patients (9.9+/-4.7 years). NGF plasma levels and QTc
      interval were measured in all patients. Student t-test was performed for
      statistical analysis. NGF plasma levels were significantly lower in Rett patients
      with QTc interval prolongation (QTc > 0.44 sec) in comparison with Rett patients
      with a normal QTc interval (4.5+/-4.5 vs 11+/-8.3 pg/ml, p = 0.02). The
      alteration of NGF levels, observed in Rett patients with a long QTc interval, may
      explain the presence of an altered ventricular repolarization associated with a
      higher risk of cardiac arrhythmias.

PMID- 14708070
TI  - Inflammation and nutrition in renal insufficiency.
AB  - Protein-energy malnutrition (PEM) and inflammation are common in patients with
      chronic kidney disease (CKD) and worsen as the CKD progresses toward the end
      stage renal disease (ESRD). These conditions are major predictors of poor
      clinical outcome in kidney failure, as reflected by a strong association between
      hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that
      inflammation is the cause of both PEM and CVD and, hence, the main link among
      these conditions, but these hypotheses are not well established. Increased
      release or activation of inflammatory cytokines, such as interleukin-6 or tumor
      necrosis factor alpha, may suppress appetite, cause muscle proteolysis and
      hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of
      proinflammatory cytokines caused by reduced renal function, volume overload,
      oxidative or carbonyl stress, decreased levels of antioxidants, increased
      susceptibility to infection in uremia, and the presence of comorbid conditions
      may lead to inflammation in CKD patients. In hemodialysis patients, the exposure
      to dialysis tubing and dialysis membranes, poor quality of dialysis water, back
      filtration or back-diffusion of contaminants, and foreign bodies in dialysis
      access maybe additional causes of inflammation. Similarly, episodes of overt or
      latent peritonitis, peritoneal dialysis (PD) catheter and its related infections,
      and constant exposure to PD solution may contribute to inflammation in these
      patients. The degree to which PEM in dialysis patients is caused by inflammation
      is not clear. Because both PEM and inflammation are strongly associated with each
      other and can change many nutritional measures and outcome concurrently in the
      same direction, the terms malnutrition-inflammation complex syndrome (MICS)
      and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to
      denote the important contribution of both of these conditions to poor clinical
      outcome. Maintenance dialysis patients who are underweight or who have low serum
      levels of cholesterol, creatinine, or homocysteine may be suffering from the
      MICS/MIA and its subsequent poor outcome. Consequently, obesity and
      hypercholesterolemia may appear protective, which is known as reverse
      epidemiology. Although MICS/MIA may have a significant contribution in reversing
      the traditional CVD risk factors in dialysis patients, it is not clear whether
      PEM or inflammation and their complications can be effectively managed in CKD and
      ESRD or whether their management improves clinical outcome.

PMID- 14708068
TI  - Right ventricular volume measurements in ventilated preterm neonates.
AB  - Pulmonary hypertension is associated with worse perinatal outcomes in infants
      with respiratory disorders. In these infants, right ventricular dysfunction may
      result in poor pulmonary blood flow. The objective of this study was to follow
      changes in right ventricular volumes during the first 2 days of life in infants
      with respiratory distress syndrome. Serial echocardiographic examinations were
      performed on days 0-2 on infants ventilated for respiratory distress syndrome.
      Two-dimensional echocardiography with the ellipsoid approximation was used to
      calculate systolic and diastolic volumes. In 17 ventilated preterm infants, right
      ventricular volumes were significantly lower on day 2 compared with day 0 and
      decreased from a median (interquartile range) end systolic volume of 0.80 ml/kg
      (0.66-0.91 ml/kg) to 0.45 ml/kg (0.39-0.54 ml/kg) ( p < 0.001). End diastolic
      volume decreased from a median (interquartile range) of 1.54 ml/kg (1.44-1.65
      ml/kg) to 1.30 ml/kg (1.22-1.60 ml/kg) ( p = 0.039). Right ventricular ejection
      fraction increased from a median (interquartile range) of 0.48 ml/kg (0.44-0.56
      ml/kg) to 0.62 ml/kg (0.58-0.71 ml/kg) during the same period ( p < 0.001), as
      did right ventricular output from a median (interquartile range) 120 ml/kg/min
      (96-125 ml/kg/min) to 140 ml/kg/min (113-168 ml/kg/min) ( p = 0.044). Right
      ventricular volume decreases during the first 2 days of life in ventilated
      preterm infants. However, right ventricular performance is maintained.

PMID- 14708071
TI  - Trace elements and vitamins in maintenance dialysis patients.
AB  - Although protein-energy malnutrition occurs commonly in patients with end-stage
      renal disease undergoing maintenance dialysis treatment, it is not the only form
      of malnutrition that may exist in these individuals. They may also suffer from
      deficiencies of micronutrients, particularly trace elements and vitamins. More
      commonly occurring vitamin deficiencies in maintenance dialysis patients include
      those for vitamin C (ascorbate), folate, vitamin B6 (pyridoxine), and 1,25
      dihydroxycholecalciferol (calcitriol). Among trace elements, deficiencies may
      occur more commonly for iron, zinc, and possibly selenium, whereas toxicities are
      more common with aluminum and possibly copper. Evidence suggests that there is an
      abnormally high prevalence of antioxidant deficiency in maintenance dialysis
      patients, especially because a low intake of protein and energy may be associated
      with inadequate ingestion of antioxidant vitamins (ie, vitamins E and C and
      carotenoids). Thus, some micronutrient deficiencies in maintenance dialysis
      patients may contribute to the development of atherosclerotic cardiovascular
      disease. Dietary requirements for vitamins and trace elements in maintenance
      dialysis patients are reviewed and the recommended daily intakes are discussed.

PMID- 14708072
TI  - Nutritional requirements in maintenance hemodialysis.
AB  - There is a high prevalence of nutritional disorders in maintenance hemodialysis
      patients. This fact has been recently confirmed because larger routine
      assessments of MHD patients body composition are now performed. Food records and
      dietary interviews show spontaneous low intakes of protein and energy in many
      patients. An increasing dialysis dose above a Kt/V (single pool) of 1.5 may not
      improve patients nutritional intakes. Inflammation may further impair the balance
      between protein synthesis and catabolism and cause anorexia. In response to these
      abnormalities, the management of energy, protein, vitamins, and trace elements
      intake will be discussed with special emphasis on calcium, phosphorus, enteral
      support, and parenteral nutrition.

PMID- 14708073
TI  - Protein and energy nutrition among adult patients treated with chronic peritoneal
      dialysis.
AB  - Protein-energy malnutrition (PEM) in adult patients treated with chronic
      peritoneal dialysis (CPD), which is highly prevalent and frequently severe in its
      manifestation, poses a significant therapeutic dilemma. The causes of PEM include
      inflammation, low nutrient intake, nutrient losses during dialysis, metabolic
      acidemia, coexisting illnesses, and possibly the endocrine disorders of uremia.
      Treatment strategies for PEM in CPD patients include the following: attempt to
      treat the potentially reversible causes of anorexia, increase nutrient intake (by
      nutritional counseling, oral food supplements, consideration of appetite
      stimulants and intraperitonial amino acid solutions), and the correction of
      metabolic acidosis. Coexisting illnesses engendering PEM should be treated.
      Experimental evidence suggests that such agents as anabolic steroids, human
      growth hormone, insulin-like growth factor-I, and L-carnitine may engender
      positive protein balance in these individuals. Finally, the use of anti
      inflammatory agents to improve the nutritional status of malnourished CPD
      patients remains to be defined. There is a need to carry out clinical trials that
      examine whether an improvement in the nutritional status of CPD patients is
      associated with an improvement in their mortality, morbidity and/or quality of
      life.

PMID- 14708074
TI  - Malnutrition and nutritional therapy of chronic kidney disease in developing
      countries: the Asian perspective.
AB  - There is a paucity of data regarding the prevalence and clinical consequences of
      protein-energy malnutrition (PEM) in the chronic renal failure, maintenance
      dialysis, and renal transplant population in developing countries. Malnutrition,
      which is reported to be present in 42% to 77% of the end-stage renal disease
      population in developing countries, is strongly associated with morbidity and
      mortality. Many religious practices in developing countries promote abstinence
      from meat, fish, and eggs. Both a vegetarian dietary pattern, which is being
      adopted by an increasing number of people, and ingestion of inadequate protein
      and calories in the diet to arrest the progression of chronic renal failure, may
      lead to malnutrition. The attendant complications of PEM, malaise, wasting,
      anemia, and decreased immunity, may predispose these patients to infections. This
      is commonly seen in both the maintenance hemodialysis and peritoneal dialysis
      population and may decrease their survival. There is an urgent need for
      nutritional counseling by a dietitian to contain the damage of malnutrition and
      to provide important nutritional information to the patient. Consultation with a
      dietitian should take place at least 3 times yearly and, in malnourished
      patients, more often, as needed. Dietetic documentation should include reports of
      food intake, subjective global assessment, anthropometric measurements,
      estimation of the nPNA, serum albumin, and prealbumin, the serum lipid profile,
      sodium and potassium intake, calcium and phosphorus status, and any changes in
      body weight.

PMID- 14708077
TI  - Serum albumin measurement in dialysis patients: should it be a measure of
      clinical performance?

PMID- 14708078
TI  - Why measure serum albumin levels?

PMID- 14708079
TI  - Inflammatory markers are unrelated to physical activity, performance, and
      functioning in hemodialysis.
AB  - OBJECTIVE: To determine the associations among dietary intake and inflammatory
      cytokines with physical activity, function, and performance in maintenance
      dialysis patients. DESIGN: Cross-sectional analysis of cohort study. SETTING:
      University-affiliated dialysis units, general clinical research center. SUBJECTS:
      Multiethnic cohort of maintenance hemodialysis patients. MAIN OUTCOME MEASURES:
      Physical activity by accelerometry; physical performance by gait speed, stair
      climbing, and chair raising; physical functioning by the Medical Outcomes Study
      Short Form 36-item questionnaire subscale scores; and maximal and adjusted
      activity scores of human activity profile. RESULTS: Levels of inflammatory
      cytokines were uniformly high. Tumor necrosis factor-alpha was directly
      correlated with dietary protein and energy intake; no other cytokines were
      directly or inversely correlated with intake. Dietary intake was associated with
      physical activity, as expected, and not significantly associated with performance
      or function (with the exception of gait speed). There were no significant
      associations among inflammatory cytokines and physical activity, performance, or
      function. CONCLUSION: Although dietary intake and inflammation may independently
      influence traditional proxies of nutritional status, this analysis provides no
      evidence for a link between cytokines and physical activity, performance, or
      function in hemodialysis patients. More research is required to understand the
      role of cytokines in protein energy malnutrition and the mechanisms of wasting
      and functional decline in the dialysis population.

PMID- 14708080
TI  - Vitamin D analogs in uremia: integrating medical and nutritional issues.
AB  - A system of regulatory molecules interacts at the cellular level to control and
      coordinate the many metabolic pathways that constitute normal mineral metabolism.
      Alterations that occur in uremia profoundly disrupt this intricate system of
      regulation. A lack of control poses serious consequences for patients with
      chronic renal disease, and restoring some level of control represents a
      significant treatment goal. To achieve adequate treatment, it is necessary to
      correct aberrations in the metabolism of the major regulatory molecules,
      parathyroid hormone, vitamin D, calcium, and phosphorus. The use of vitamin D
      hormone replacement therapy is one important part of this strategy, and the
      availability of newer vitamin D compounds may prove to be especially beneficial.
      The effective use of these compounds, nevertheless, depends on the coordinated
      efforts of each member of the health care team to design and implement an
      integrated treatment protocol that recognizes all aspects of intervention.

PMID- 14708081
TI  - Successful treatment of a LifeSite Hemodialysis Access System pocket infection
      with large-volume kanamycin solution irrigation.
AB  - Bridge devices-dialysis catheters and subcutaneous access devices-play a critical
      role in increasing the placement of arteriovenous (AV) fistulas by providing
      hemodialysis vascular access while AV fistulas mature. The LifeSite Hemodialysis
      Access System (Vasca Inc, Tewskburg, MA), a fully implantable, subcutaneous dual
      valve access system, has been shown to have lower complication rates, higher
      blood flow rates, and better long-term device survival than conventional tunneled
      hemodialysis catheters, indicating it may better meet the requirements for
      optimally bridging to a fistula. This case study of a 48-year-old black man
      undergoing chronic hemodialysis for renal failure because of insulin-dependent
      diabetes describes a simple approach for resolving localized pocket infections
      associated with the LifeSite System by drip irrigation of the valves and tissue
      pockets with an antibiotic solution. Eight weeks after implantation of the
      LifeSite System, the patient exhibited symptoms of infection of the lateral
      LifeSite valve tissue pocket, which on culture was shown to be caused by
      Staphylococcus aureus. Flushing the LifeSite valve and tissue pocket with a large
      volume of kanamycin solution, in conjunction with intravenous vancomycin and
      routine irrigation of the valve with isopropyl alcohol, resolved the infection
      after 1 treatment. The LifeSite System successfully bridged the patient to a
      transposed basilic vein fistula created through a 2-stage surgical procedure. The
      LifeSite System provided uninterrupted access for hemodialysis over a period of 6
      months while the fistula matured. The LifeSite System should allow surgeons to
      attempt fistula construction in more patients, including diabetics, access
      challenged patients, and patients with small vessels, who may benefit from a
      nontraditional surgical approach toward fistula creation.

PMID- 14708086
TI  - Stress response of yeast candida intermedia to Cr(VI).
AB  - Stress response of yeast Candida intermedia ZIM 156 exposed to chromium(VI) was
      investigated. Yeast cells were treated with Cr(VI) in concentrations of 50, 100,
      300 and 500 microM in the mid-exponential growth phase. Monitoring of some
      bioprocess parameters during growth, specifically pO(2), showed that Cr(VI)
      addition, specifically in concentration of 100 and partially 50 micromol/L,
      increased metabolism intensity, which is connected to induced stress responses.
      Furthermore, oxidation of 2',7'-dichlorofluorescin indicated increased
      intracellular oxidant level, specifically at 100 microM Cr(VI) concentration.
      Antioxidant defense systems were further investigated. Catalase and superoxide
      dismutase activity was not increased in the cells exposed to the both Cr(VI)
      concentrations, which indicate that catalase and superoxide dismutase do not
      participate in cell defense systems. In contrast intracellular glutathione
      content in reduced form increased significantly in the cells exposed to 100
      micromol Cr(VI)/L. Therefore, we demonstrated that glutathione plays an important
      role in the stress response of C. intermedia to Cr(VI).

PMID- 14708085
TI  - The use of c-src knockout mice for the identification of the main toxic signaling
      pathway of TCDD to induce wasting syndrome.
AB  - The effect of single intraperitoneal injection of 115 microg/kg of TCDD (i.e.,
      approximately 1/2 of LD50) to male C57BL/6 mice on the liver mRNA expression
      changes of several growth factor related genes was assessed at 3 h, 24 h, 10
      days, and 30 days posttreatment. The results revealed that the most consistently
      elevated mRNAs during the entire test period were those of c-Src, TGFalpha, and
      PDGFa. In contrast, those observed to be consistently suppressed were mRNAs for
      EGF receptor (EGFR), Ki-Ras, SAPKK, Sp-1, C/EBPbeta, and NFkB. Elevation of mRNAs
      for TGFbeta and STAT3 was observed only on day 10 and day 30. To assess the role
      of c-Src in the above action of TCDD, we conducted a parallel study with congenic
      C57BL/6 male c-src -/- mice. The results showed that in scr -/- mice the effect
      of TCDD was less in the case of mRNA expression of PDGF(AA), STAT3, C/EPBbeta,
      NMT-1, and AP-2gamma in addition to c-src as compared to scr +/+ mice. Those
      affected least by the absence of c-Src were SAPKK, and surprisingly, EGF receptor
      mRNAs, both of which were consistently downregulated in both strains. In most of
      the other cases, the extent of TCDD-induced changes were generally less
      pronounced in src -/- mice as compared to +/+ mice. These observations support
      the notion that c-Src is an important mediator of the effects of TCDD on
      TGFalpha, PDGF(AA), and C/EBPalpha, beta.

PMID- 14708087
TI  - Goitrogenic activity of p-coumaric acid in rats.
AB  - The effects of three natural phenolic acids (caffeic, ferulic, and p-coumaric) on
      the rat thyroid gland were examined in a 3-week oral-treatment study. Forty male
      Wistar albino rats, divided into groups of 10 rats each and fed iodine-rich diet,
      were administered by gastrointestinal tube saline (control), caffeic acid,
      ferulic acid, or p-coumaric acid at a dose level of 0.25 micromol/kg/day for 3
      weeks. The mean absolute and relative thyroid weights in caffeic, ferulic, or p
      coumaric acid groups were significantly increased to 127 and 132%, 146 and 153%,
      or 189 and 201% compared to control value, respectively. Histological examination
      of the thyroids of p-coumaric acid group revealed marked hypertrophy and/or
      hyperplasia of the follicles. Caffeic or ferulic groups showed slight to moderate
      thyroid gland enlargement. Thyroid lesions in p-coumaric acid group were
      associated with significant increases in cellular proliferation as indicated by
      [(3)H]thymidine incorporation. In addition, the goitrogenic effect of p-coumaric
      acid was further confirmed by significant decreases (50%) in serum tri
      iodothyronine (T(3)) and thyroxine (T(4)), and a parallel increase (90%) in serum
      thyroid stimulating hormone (TSH) compared to control group. These results
      indicate that administration of p-coumaric acid at relatively high doses induces
      goiter in rats.

PMID- 14708088
TI  - 2'-Deoxyadenosine causes apoptotic cell death in a human colon carcinoma cell
      line.
AB  - The combination of 2'-deoxyadenosine and 2'-deoxycoformycin is toxic for the
      human colon carcinoma cell line LoVo. In this study we investigated the mode of
      action of the two compounds and have found that they promote apoptosis. The
      examination by fluorescence microscopy of the cells treated with the combination
      revealed the characteristic morphology associated with apoptosis, such as
      chromatin condensation and nuclear fragmentation. The occurrence of apoptosis was
      also confirmed by the release of cytochrome c and the proteolytic processing of
      procaspase-3 in cells subjected to the treatment. To exert its triggering action
      on the apoptotic process, 2'-deoxyadenosine enters the cells through an
      equilibrative nitrobenzyl-thioinosine-insensitive carrier, and must be
      phosphorylated by intracellular kinases. Indeed, in the present work we
      demonstrate by analysis of the intracellular metabolic derivatives of 2'
      deoxyadenosine that, as suggested by our previous findings, in the incubation
      performed with 2'-deoxyadenosine and 2'-deoxycoformycin, an appreciable amount of
      dATP was formed. Conversely, when also an inhibitor of adenosine kinase was added
      to the incubation mixture, dATP was not formed, and the toxic and apoptotic
      effect of the combination was completely reverted.

PMID- 14708089
TI  - Purification and characterization of rat pancreatic fatty acid ethyl ester
      synthase and its structural and functional relationship to pancreatic cholesterol
      esterase.
AB  - Formation of fatty acid ethyl esters (FAEEs, catalyzed by FAEE synthase) has been
      implicated in the pathogenesis of chronic pancreatitis. In previous studies, we
      demonstrated that FAEE synthase, purified from rat liver microsomes, is identical
      to rat liver carboxylesterase (pI 6.1), and structurally and functionally
      different than that from pancreas. In this study, we purified and characterized
      rat pancreatic microsomal FAEE synthase, and determined its relationship with rat
      pancreatic cholesterol esterase (ChE). Since most of the serine esterases express
      p-nitrophenyl acetate (PNPA)-hydrolyzing activity as well as synthetic activity
      to form fatty acid esters or amides with a wide spectrum of alcohols and amines,
      respectively, we used PNPA-hydrolyzing activity to monitor the purification of
      FAEE synthase during various chromatographic purification steps. Synthesizing
      activity towards FAEEs, fatty acid methyl esters, and fatty acid anilides was
      measured only in the pooled fractions. At each step of purification (ammonium
      sulfate saturation, Q Sepharose XL, and heparin-agarose column chromatographies,
      and high performance liquid chromatography (anion exchange and gel filtration))
      synthetic as well as hydrolytic activities copurified. Using ethanol, methanol,
      or aniline as substrates, the ester or anilide synthesizing activity of the
      purified protein was found to be 8709, 13000, and 2201 nmol/h/mg protein,
      respectively. The purified protein displayed a single band with an estimated
      molecular mass of approximately 68 kD upon SDS-PAGE under reduced denaturing
      conditions, cross-reacted with antisera against rat pancreatic ChE and showed
      100% N-terminal sequence homology of the first 15 amino acids to that of rat
      pancreatic ChE. These results suggest that the purified protein has broad
      substrate specificity towards the conjugation of endogenous long chain fatty
      acids with substrates having hydroxyl and amino groups and is identical to ChE.

PMID- 14708090
TI  - Axial skeletal and Hox expression domain alterations induced by retinoic acid,
      valproic acid, and bromoxynil during murine development.
AB  - Retinoic acid (RA) alters the developmental fate of the axial skeletal anlagen.
      "Anteriorizations" or "posteriorizations," the assumption of characteristics of
      embryonic areas normally anterior or posterior to the affected tissues, are
      correlated with altered embryonal expression domains of Hox genes after in utero
      RA treatment. These "homeotic" changes have been hypothesized to result from
      alterations of a "Hox cod" which imparts positional identity in the axial
      skeleton. To investigate whether such developmental alterations were specific to
      RA, or were a more general response to xenobiotic exposure, CD-1 pregnant mice
      were exposed to RA, valproic acid (VA), or bromoxynil (Br) during organogenesis.
      Additionally, the expression domains of two Hox genes, Hoxa7 and Hoxa10, were
      examined in gestation day (GD) 12.5 embryos obtained from control, RA, VA, or Br,
      treated gravid dams exposed on GD 6, 7, or 8. The anterior expression boundary of
      Hoxa7 is at the level of the C7/T1 vertebrae and that of Hoxa10 is at L6/S1.
      Compound-induced changes in the incidence of skeletal variants were observed.
      These included supernumerary cervical ribs (CSNR) lateral to C7, 8
      vertebrosternal ribs, supernumerary lumbar ribs (LSNR) lateral to L1, extra
      presacral vertebrae, and the induction of vertebral and/or rib malformations. RA
      and VA administration on GD 6 caused posteriorization in the cervico-thoracic
      region (CSNR) while GD 8 exposure to any of the three compounds resulted in
      anteriorizations in the thoraco-lumbar area (LSNR and an increase in the number
      of presacral vertebrae). These effects occurred across regions of the axial
      skeleton. Analysis of gene expression demonstrated changes in the anterior
      boundaries of Hoxa7 expression domains in embryos treated on GD 6 and 8 with RA.
      VA and Br did not induce any statistically significant alterations in Hoxa7 and
      none of the compounds caused alterations in Hoxa10 expression domains. The
      studies indicate that RA GD 6 treatment-induced Hoxa7 shifts were rostral
      (posteriorization) while the RA-induced GD 8 anterior expression boundary shift
      was caudal (anteriorization), correlating with the axial skeletal changes noted.
      These data suggest that xenobiotic compounds such as VA and Br may induce similar
      axial skeletal changes by affecting different components of the developmental
      processes involved in the patterning of the axial skeleton.

PMID- 14708091
TI  - Vanadium inhibits placental glutathione S-transferase (GST-P) positive foci in
      1,2-dimethyl hydrazine induced rat colon carcinogenesis.
AB  - Vanadium (V) has recently been found to possess potent anti-neoplastic activity
      in rat colon carcinogenesis. In the present study attempts have been made to
      investigate the expression of the number and area of aberrant crypt foci positive
      for placental glutathione S-transferase (GST-P) during 1,2-dimethyl hydrazine
      (DMH)-induced rat colon carcinogenesis. Male Sprague Dawley rats were randomly
      divided into four groups. Rats in group A were designed as normal controls. Group
      B animals received DMH once a week (20 mg/kg body wt.) intraperitoneally for 16
      weeks. Group C rats received the same treatment of DMH as in group B, along with
      0.5-ppm vanadium as ammonium monovanadate ad libitum in drinking water throughout
      the experiment. Vanadium alone was given to Group D rats without any DMH
      injection. The expression of the number and the area of aberrant crypt foci (ACF)
      positive for GST-P was maximum in DMH-treated group. Vanadium-treated rats
      significantly reduced (P < 0.001) the expression of GST-P positive ACF cells (by
      71.13%) for the entire period of the study. Moreover the histopathological
      examination also showed that vanadium action could minimize the aberrant crypt
      foci (P < 0.001). Furthermore, vanadium supplementation also elevated SOD
      activities in both liver and colon (P < 0.01, P < 0.02 and P < 0.01, P < 0.02
      respectively) when compared to their carcinogen counterparts. Our results confirm
      that vanadium is particularly effective in limiting the action of the carcinogen,
      thereby establishing its anticarcinogenicity in chemically induced rat colon
      carcinogenesis.

PMID- 14708092
TI  - Garlic attenuates chrysotile-mediated pulmonary toxicity in rats by altering the
      phase I and phase II drug metabolizing enzyme system.
AB  - Asbestos and its carcinogenic properties have been extensively documented.
      Asbestos exposure induces diverse cellular events associated with lung injury.
      Previously, we have shown that treatment with chrysotile shows significant
      alteration in phase I and phase II drug metabolizing enzyme system. In this study
      we have examined some potential mechanisms by which garlic treatment attenuates
      chrysotile-mediated pulmonary toxicity in rat. Female Wistar rats received an
      intratracheal instillation of 5 mg chrysotile (0.5 mL saline) as well as
      intragastric garlic treatment (1% body weight (v/w); 6 days per week). Effect of
      garlic treatment was evaluated after 1, 15, 30, 90, and 180 days by assaying aryl
      hydrocarbon hydroxylase (AHH), glutathione (GSH), glutathione S-transferase
      (GST), and production of thiobarbituric acid reactive substances (TBARS) in rat
      lung microsome. The results showed that AHH and TBARS formation were
      significantly reduced at day 90 and day 180 in chrysotile treated garlic cofed
      rats; GSH recovered 15 days later to the near normal level and GST elevated
      significantly after treatment of garlic as compared to chrysotile alone treated
      rat lung microsome. The data obtained shows that inhibition of AHH activity and
      induction of GST activity could be contributing factor in chrysotile-mediated
      pulmonary toxicity in garlic cofed rats. However, recovery of GSH and inhibition
      of TBARS formation by garlic and its constituent(s) showed that garlic may give
      protection by altering the drug metabolizing enzyme system.

PMID- 14708093
TI  - Prevalence of congenital cardiovascular malformations among relatives of infants
      with hypoplastic left heart, coarctation of the aorta, and d-transposition of the
      great arteries.
AB  - Cardiovascular malformations (CVM) are the most common birth defects and carry
      significant and lifelong personal and societal costs. Research into genetic and
      environmental risk factors is therefore critical in identifying clues to
      causation and prevention. The purpose of this study was to investigate patterns
      of familial aggregation in CVM, specifically among infants with left-sided
      obstructive heart defects. We ascertained families of probands with hypoplastic
      left heart (HLH: N = 38), coarctation of the aorta (CoA: N = 46), and d
      transposition of the great arteries (dTGA: N = 22). First degree relatives had
      clinical examinations and echocardiograms; all other relatives had detailed
      reviews of medical records. A total of 2,694 relatives were included in the
      study: 379 1st degree, 986 2nd degree, and 1,329 3rd degree. Mean nuclear family
      size and sibship size were similar among the groups. CVM were detected more
      frequently in 1st degree relatives of probands with HLH (19.3%) or CoA (9.4%)
      than among dTGA families (2.7%). The proportions of affected 2nd degree relatives
      were similar across groups (</=1%). In 3rd degree relatives, CVM was detected in
      1.8% of the HLH families compared to 1.2% in CoA and 0.4% in dTGA families. The
      predominant types of CVM among relatives of HLH and CoA probands were left-sided
      obstructive lesions, in 72% (21 of 29) and 67% (25 of 37) of the affected
      relatives, respectively. Familial aggregation of these types of CVM is therefore
      confirmed in this study, potentially facilitating the search for specific genetic
      and other risk factors in recurrent CVM.

PMID- 14708094
TI  - Autosomal recessive frontotemporal pachygyria.
AB  - Pachygyria is a cortical malformation that results from the abnormal migration of
      neurons. Regions of the brain with pachygyria have an abnormally thick cortex
      that lacks normal folding and has deficient layering. We describe three siblings,
      born to nonconsanguineous Mexican parents, who have bilateral frontotemporal
      pachygyria without polymicrogyria. The pachygyria is accompanied by moderate
      mental retardation, esotropia, and either hypertelorism or telecanthus. They are
      otherwise morphologically normal and do not have microcephaly. Two experienced a
      single seizure in infancy. The characteristic phenotype present in this family
      suggests a new genetic syndrome that is likely inherited as an autosomal
      recessive trait.

PMID- 14708096
TI  - A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially
      causative of malignant hyperthermia, central core disease, and severe skeletal
      malformation.
AB  - Malignant hyperthermia susceptibility (MHS) and central core disease (CCD) have
      been shown to result from missense mutations in the ryanodine receptor gene of
      the skeletal muscle (RYR1). A 15-year-old patient who had spondylocostal
      dysostosis (SCD) developed an MH crisis during general anesthesia. The patient
      was characterized phenotypically by block vertebrae, vertebral fusion, short neck
      and thorax, fused ribs, craniofacial abnormalities, spina bifida occulta, and a
      diaphragmatic defect closed surgically in early infancy. The diagnosis MH
      susceptible (MHS) was confirmed by the in vitro contracture test (IVCT) on a
      muscle biopsy. Surprisingly, the histopathological investigation revealed the
      presence of CCD too. Molecular genetic investigation of the RYR1 gene was
      performed to search for known MH-related mutations. Cluster regions of the RYR1
      gene, in which mutations have already been found, were examined by direct
      automated sequencing. In addition to the diagnosis MHS and CCD we were able to
      identify a novel RYR1 mutation in exon 46: 7358ATC > ACC, resulting in an
      Ile2453Thr substitution. This mutation was also present in the mother, in whom MH
      disposition and CCD were determined by muscle investigations. We suggest that the
      newly identified RYR1 mutation is closely associated with MH and CCD. A probable
      causative role of the RYR1 gene in SCD patients should be assessed by further
      genetic investigations.

PMID- 14708095
TI  - Bilaterally asymmetric effects of quantitative trait loci (QTLs): QTLs that
      affect laxity in the right versus left coxofemoral (hip) joints of the dog (Canis
      familiaris).
AB  - In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is
      frequent and heritable, providing a genetic model for some aspects of the human
      disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait
      loci (QTLs) that regulate laxity in the hip joint. A population of 286 PWDs, each
      characterized by ca. 500 molecular genetic markers, was analyzed for subluxation
      of the hip joint as measured by the Norberg angle, a quantitative radiographic
      measure of laxity. A significant directed asymmetry was observed, such that
      greater laxity was observed in the left than the right hip. This asymmetry was
      not heritable. However, the average Norberg angle was highly heritable as were
      the Norberg angles of either the right or left hips. After correction for
      pedigree effects, two QTLs were identified using the metrics of the left and
      right hips as separate data sets. Both are on canine chromosome 1 (CFA1),
      separated by about 95 Mb. One QTL, associated with the SSR marker FH2524 was
      significant for the left, but not the right hip. The other, associated with
      FH2598, was significant for the right but not the left hip. For both QTLs, some
      extreme phenotypes were best explained by specific interactions between
      haplotypes.

PMID- 14708097
TI  - Onset and progression of disease in familial and sporadic Parkinson's disease.
AB  - Lately different and rare genetic forms of Parkinson's disease (PD) have been
      described. Complete genomic screening has suggested that still undefined multiple
      genetic factors might underlie the development of PD. The course of PD patients
      with and without genetic background might be different. We compared the age at
      onset and progression of PD with (FH) and without (NFH) family history. Two
      hundred forty PD patients attending the outpatient Movement Disorders Clinic were
      evaluated. The age of onset (AO), the duration of disease until stage III of
      Hoehn and Yahr (YST3), until dementia (YDEM) and family history of PD were
      determined by interview, examination of medical files and of affected family
      members. Patients with young onset who reported another PD patient among their
      siblings were tested for parkin mutations. Statistical analysis used ANOVA,
      Fisher's Least Significant Difference, log-rank and Wilcoxon's tests for Kaplan
      Meier survival curves taking stage III and dementia as end-points. Of the 240
      patients (age 73.3 +/- 10.9 years), 29 (12%) had positive FH. Six of them carried
      parkin mutations. The AO was 33.5 +/- 8.1 (range 19-42) years for parkin
      carriers, 59.3 +/- 11.3 (range 34-76) for FH and 66.5 +/- 11.8 (27-91) years for
      NFH (P < 0.0001). The three groups were significantly different from each other
      (alpha = 0.05). Stage III and dementia were reached only in non-parkin patients.
      YST3 was 12.6 +/- 6.6 years for FH and 6.5 +/- 5.0 years for NFH (P < 0.0001).
      YDEM was 10.1 +/- 6.0 years for FH versus 4.7 +/- 4.5 years for NFH (P = 0.002).
      Kaplan-Meier survival analysis revealed faster motor (P = 0.0016) and mental
      decline (P = 0.02) in NFH versus FH. Our results showed that the AO of PD is
      younger in patients with FH. Motor and mental deterioration, however, showed a
      less steep course in familial PD patients.

PMID- 14708098
TI  - Complex chromosome re-arrangement 45,X,t(Y;9) in a girl with sex reversal and
      mental retardation.
AB  - A girl with mental retardation and multiple minor anomalies was found to have a
      complex chromosome 9p re-arrangement comprising a deleted, translocated Y
      chromosome, a deletion of the sex reversal gene region (DMRT1) at 9p, together
      with an inverted duplication of the more proximal part of 9p. The karyotype was
      45,X,der(Y;9)(Ypter-->Yq12::9p21.1-->9p22.2::9p22.2-->9qter) de novo. The
      karyotypic male, phenotypic female had a dysgerminoma of the left dysplastic
      ovary. The patient had typical 'trisomy 9p' syndrome, and we propose that the
      critical region for this phenotype is located between 9p22.1 and 9p22.2.

PMID- 14708099
TI  - "Everybody in the world is my friend" hypersociability in young children with
      Williams syndrome.
AB  - Williams syndrome (WS) is a rare genetic disorder involving a characteristic
      cardiac defect, typical facial appearance, and an uneven profile of cognitive
      strengths and weaknesses. WS is caused by a hemizygous deletion in chromosome
      band 7q11.23, including the gene for elastin (ELN). Typically, individuals with
      WS seem driven to greet and interact with strangers. The goal of the present
      study was to investigate age-related changes in the expression of
      hypersociability in WS. Parents of 64 children with WS, 31 children with Down
      syndrome (DS), and 27 normal controls (NC) provided data concerning specific
      aspects of their children's social behavior using the Salk Institute Sociability
      Questionnaire (SISQ). Children ranged in age from 1 year, 1 month to 12 years, 10
      months. Consistent with earlier findings, whole group analyses showed the WS
      group to be significantly higher on all aspects of sociability studied.
      Comparisons among the groups at different ages revealed that hypersociability is
      evident even among very young children with WS, and, significantly, children with
      WS exceed children with DS with respect to Global Sociability and Approach
      Strangers in every age group. The findings from children who have the typical
      deletion for WS are contrasted with data obtained from a young child with WS who
      has a smaller deletion and many physical features of WS, but who does not
      demonstrate hypersociability, providing intriguing clues to a genetic basis of
      social behavior in this syndrome. These data suggest the involvement of a genetic
      predisposition in the expression of hypersociability in WS.

PMID- 14708100
TI  - Mosaic paternal uniparental (iso)disomy for chromosome 20 associated with
      multiple anomalies.
AB  - Uniparental disomy for a number of human chromosomes is associated with clinical
      abnormalities. We report a child with a complex chromosomal rearrangement
      involving chromosome 20 (45,XY,psu dic (20;20)(p13;p13)) and paternal uniparental
      isodisomy for chromosome 20 in peripheral blood and bone marrow. This patient had
      multiple congenital abnormalities including microtia/anotia, micrencephaly,
      congenital heart disease, neuronal subependymal heterotopias, and colonic
      agangliosis. Molecular studies on DNA from peripheral blood demonstrated paternal
      uniparental inheritance of chromosome 20. However, fibroblasts demonstrated a
      mosaic karyotype, with one cell line having 45 chromosomes, including the
      pseudodicentric chromosome 20 (75% of cells), and a second cell line having 46
      chromosomes, including the pseudodicentric chromosome 20, and a normal chromosome
      20 (trisomy 20) (25% of cells). FISH experiments using a sub-telomeric probe that
      maps approximately 120 kb from the 20p telomere, showed that both copies of these
      sequences were present on the rearranged chromosome, consistent with deletion of
      a very small interval. This leads us to suggest that in addition to trisomy 20
      mosaicism, paternal uniparental disomy for chromosome 20 could contribute to his
      clinical phenotype.

PMID- 14708101
TI  - FOXC1 gene deletion is associated with eye anomalies in ring chromosome 6.
AB  - We report a case of ring chromosome 6 presenting with growth and mental
      retardation, cerebral dysgenesis, eye malformations, mixed hearing loss, and
      abnormal physical features. Fluorescent in situ hybridization (FISH) and
      microsatellite genotyping demonstrated segmental deletions of less than 6 Mb on
      6p and 1-2 Mb on 6q. The primary karyotype is designated as
      46,XY,r(6)(p25q27).ish r(6)(p25.1q27)(D6S344-, FOXC1-, D6S1574+, D6S281-,
      D6S297+). Secondary structural and numerical variants of the ring 6 were observed
      in 16% of the cells analyzed. Intragenic genotyping revealed deletion of the
      paternal FOXC1 gene, haploinsufficiency of which has been reported to cause eye
      anterior chamber developmental defects. Accordingly, we propose that our
      patient's ophthalmologic abnormalities result from haploinsufficiency of the
      transcription factor FOXC1. We present clinical and cytogenetic summaries on 23
      reported cases of ring 6 and categorize them into mild, moderate, and severely
      affected groups. Further phenotype comparisons between cases with ring 6 and
      cases with only 6p or 6q terminal deletions suggest that genes important for
      hearing, vision, and central nervous system development remain to be identified
      in chromosome 6 terminal regions. Molecular definition of the fusion points and
      tissue mosaicism studies are necessary to better understand the genotype
      phenotype correlation of ring 6. We recommend ophthalmology, audiology,
      cardiology, and central nervous system examinations be part of the routine
      evaluation for children with a ring chromosome 6.

PMID- 14708102
TI  - Mosaic trisomy 11p in monozygotic twins with discordant clinical phenotypes.
AB  - We report on monozygotic (MZ) twins with a de novo mos
      46,XX,der(15)t(11;15)(p12;p11.2)/46,XX karyotype varying in different tissues.
      The clinical presentation and findings at the cytogenetic level are described.
      One of the infants had definite minor anomalies at birth, also found in other
      cases of trisomy of 11p resembling the Beckwith-Wiedemann syndrome. Theoretical
      backgrounds regarding the string of events leading to the cytogenetic findings in
      these twins and the various factors that might have contributed to the
      dissimilarities in phenotype between these twins are discussed.

PMID- 14708103
TI  - Lissencephaly with der(17)t(17;20)(p13.3;p12.2)mat.
AB  - The isolated lissencephaly sequence may be caused by point mutations of the LIS1
      gene or by FISH-detectable microdeletions of the 17p13.3 region, which carries
      the LIS1 gene. These have various patterns of phenotypic presentations, including
      the Miller-Dieker syndrome (MDS). Approximately 20% of these deletions are
      associated with a derivative chromosome 17 inherited from a parent who has a
      balanced reciprocal translocation involving chromosome 17 and another chromosome.
      We report a case of lissencephaly associated with a maternally inherited
      unbalanced translocation involving chromosome arms 17p and 20p. This results in
      partial monosomy of 17p13.3-->pter and partial trisomy of 20p12.2-->pter. To our
      knowledge, this is the first report of a reciprocal translocation between 17p and
      20p. Our patient has a combination of findings of the MDS and trisomy 20p, along
      with several unique anomalies not described in either of those two conditions.
      This report may contribute to the delineation of a phenotype resulting from
      partial monosomy 17p and partial trisomy of 20p.

PMID- 14708104
TI  - Gonadal mosaicism in severe Pallister-Hall syndrome.
AB  - Pallister-Hall syndrome (PHS, MIM #146510) is characterized by central and
      postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate
      anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited
      in an autosomal dominant pattern. Here, we describe a family with two affected
      children manifesting severe PHS with mental retardation, behavioral problems, and
      intractable seizures. Both parents are healthy, with normal intelligence, and
      have no malformations on physical, laryngoscopic, and cranial MRI exam. The
      atypical presentation of these children and the absence of parental
      manifestations suggested an autosomal recessive mode of inheritance or gonadal
      mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15
      (c.3385_3386delTT) predicting a frameshift and premature stop at codon 1129
      (p.F1129X) in the children while both parents have wild type alleles. Genotyping
      with GLI3 intragenic markers revealed that both children inherited the abnormal
      allele from their mother thus supporting gonadal mosaicism as the underlying
      mechanism of inheritance (paternity was confirmed). This is the first reported
      case of gonadal mosaicism in PHS. The severe CNS manifestations of these children
      are reminiscent of children with non-syndromic HH who often have progressive
      mental retardation with behavioral problems and intractable seizures. We conclude
      that the phenotypic spectrum of PHS can include severe CNS manifestations and
      that recurrence risks for PHS should include a proviso for gonadal mosaicism,
      though the frequency cannot be calculated from a single case report. Published
      2003 Wiley-Liss, Inc.

PMID- 14708105
TI  - A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny
      r(X) and a partial proximal duplication 1q.
AB  - A 7-year old female with global cognitive impairment, short attention span,
      hyperactivity, impulsivity, and many compulsive behaviors was referred to the
      Genetics Clinic. Height was below the 5th centile and weight was at the 5th
      centile while head circumference was at the 50th centile. Minor anomalies
      included bluish sclera, low set and slightly posteriorly rotated auricles and a
      narrow palate with marked overbite. There was no significant family history.
      Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of
      three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish
      r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient,
      suggesting the presence of an inactive X chromosome. Inactivation was confirmed
      by detection of a methylated allele of androgen receptor. This methylated allele
      was under-represented in undigested DNA, consistent with it arising from the r(X)
      which was present in only a minority of the patient's cells. The clinical
      phenotype of the tiny r(X) syndrome in our patient is obviously further
      influenced by mosaicism for the dup(1). Few cases of duplication of the proximal
      portion of chromosome 1 have been reported. Of these, the duplication either was
      present in all cells or involved different band regions so that a direct
      comparison would be difficult. However, the lower percentage of mosaicism for the
      dup(1) in our patient would suggest a milder influence on the clinical phenotype.

PMID- 14708106
TI  - Kousseff syndrome: a causally heterogeneous disorder.
AB  - The existence of Kousseff syndrome as a distinct entity has been thrown into
      doubt by a recent study conducted on the family originally reported by Kousseff.
      In all cases where chromosome 22q11.2 FISH testing has been undertaken, including
      the original sibship, a chromosome 22q11.2-microdeletion has been identified. We
      report two cases of sacral myelomeningocele associated with a conotruncal cardiac
      anomaly or "Kousseff syndrome." The first case, a 4-year-old girl, had a sacral
      myelomeningocele, tetralogy of Fallot, microcephaly, hydrocephalus, hypoplasia of
      the corpus callosum and mild-moderate developmental delay. Chromosome 22q11.2
      FISH was normal and the facial phenotype was not that of velocardiofacial
      syndrome. Sequencing of the entire coding region of CITED2 did not reveal a
      mutation. The second case, a male infant, was found to have a 22q11.2
      microdeletion. These cases confirm Kousseff syndrome to be a causally
      heterogeneous disorder.

PMID- 14708107
TI  - Independent de novo 22q11.2 deletions in first cousins with
      DiGeorge/velocardiofacial syndrome.
AB  - Deletions of chromosome 22q11.2 are found in the vast majority of patients with
      DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion
      syndrome is estimated to occur in 1 in 4,000 live births. The majority of
      deletions are de novo, with 10% or less inherited from an affected parent. Here,
      we report two separate families with recurrence of a 22q11.2 deletion in first
      cousins. In each family, unaffected siblings (brother and sister) had an affected
      child. Fluorescence in situ hybridization (FISH) studies of the parents of each
      affected child were normal and hence, relatives were not considered at an
      increased risk for recurrence in another pregnancy. We used highly polymorphic
      microsatellite repeat markers from within 22q11.2 to determine the parental
      origin of each cousin's deletion and to assess whether parental germline
      mosaicism for the 22q11.2 deletion might be a factor in these cases. This
      analysis confirmed that in each case, the deletion occurred on a chromosome 22
      derived from unrelated parents, consistent with independent de novo deletion
      events. Thus, we concluded that germline mosaicism as the underlying mechanism
      for affected cousins in these families was unlikely. Our findings underscore the
      high frequency with which the 22q11.2 deletion occurs in the general population
      and demonstrate the important role that PCR-based parental origin determination
      can have in recurrence risk counselling. Furthermore, relatives of affected
      individuals may benefit from genetic counselling and consider prenatal testing
      for the 22q11.2 deletion in future pregnancies, despite a low recurrence risk.

PMID- 14708108
TI  - Subtelomeric deletion of 18p in an adult with paranoid schizophrenia and mental
      retardation.
AB  - Chromosome anomalies are responsible for a significant proportion of patients
      with mental retardation, and congenital anomalies. Development of new molecular
      cytogenetic techniques has provided a powerful tool for detection of patients
      with subtle chromosome abnormalities. Particularly, investigation of the gene
      rich subtelomeric regions has generated interest regarding the implications and
      prevalence of cryptic chromosomal rearrangements. Here we describe an adult with
      a submicroscopic deletion of 18pter, detected by subtelomeric FISH probe. The
      patient is a 42-year-old man with a history of developmental delay, moderate
      mental retardation, and symptoms of paranoid schizophrenia since adolescence. His
      physical examination is remarkable for only a few dysmorphic findings typically
      seen in 18p- syndrome (round face, hypertelorism, down-slanted palpebral
      fissures, temporal narrowing, small hands and feet). He lacks significant short
      stature, skin changes, and associated anomalies involving internal organs. All
      known patients with deletions of the short arm of chromosome 18 have either loss
      of large parts of 18p or of the entire p-arm, or have complex chromosomal
      rearrangement involving other chromosomes. To our knowledge, this is the first
      description of a cryptic subtelomeric deletion of 18p and the first case of such
      a chromosomal anomaly in a patient with schizophrenia. Small subtelomeric
      chromosomal deletions would be missed by standard G-banded karyotyping.
      Therefore, FISH analysis using subtelomeric probes should be considered for
      diagnostic evaluation of patients with psychiatric symptoms and mental
      retardation in whom the karyotype is normal.

PMID- 14708109
TI  - Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome: report of a
      new family with additional features and review.
AB  - Two brothers with ichthyosis follicularis, noncicatricial universal alopecia,
      photophobia, hyerkeratotic psoriasis-like lesions, nails dystrophy, inguineal
      herniae, cryptorchidism, short stature, seizures, and psychomotor developmental
      delay are described. These features correspond to the ichthyosis follicularis,
      alopecia, photophobia (IFAP) syndrome. The youngest brother had in addition a
      bilateral absence of 4th fingers and camptodactyly, features never reported in
      patients with IFAP syndromes.

PMID- 14708110
TI  - What is IFAP syndrome?

PMID- 14708111
TI  - Premature centromere division versus C-anaphases in cultures: need for consensus
      and guidelines.

PMID- 14708113
TI  - The quest for the mechanisms of life.
AB  - The genomic revolution, manifested by the sequencing of the complete genome of
      many organisms, along with technological advances, such as DNA microarrays and
      developments in high-throughput analysis of proteins, metabolites, and isotopic
      tracer distribution patterns, challenged the conventional ways in which questions
      are approached in the biological sciences: (a) rather than examining a small
      number of genes and/or reactions at any one time;, we can now analyze gene
      expression and protein activity in the context of systems of interacting genes
      and gene products; (b) comprehensive analysis of biological systems requires the
      integration of all cellular fingerprints: genome sequence, maps of gene
      expression, protein expression, metabolic output, and in vivo enzymatic activity;
      and (c) collecting, managing, and analyzing comparable data from various cellular
      profiles requires expertise from several fields that transcend traditional
      discipline boundaries. While researchers in systems biology have still to address
      difficult challenges in both experimental and computational arenas, they possess,
      for the first time, the opportunity to unravel the mechanisms of life. The
      enormous impact of these discoveries in diverse areas, such as metabolic
      engineering, strain selection, drug screening and development, bioprocess
      development, disease prognosis and diagnosis, gene and other medical therapies,
      is an obvious motivation for pursuing integrated analyses of cellular systems.

PMID- 14708114
TI  - Environmental conditions and transcriptional regulation in Escherichia coli: a
      physiological integrative approach.
AB  - Bacteria develop a number of devices for sensing, responding, and adapting to
      different environmental conditions. Understanding within a genomic perspective
      how the transcriptional machinery of bacteria is modulated, as a response for
      changing conditions, is a major challenge for biologists. Knowledge of which
      genes are turned on or turned off under specific conditions is essential for our
      understanding of cell behavior. In this study we describe how the information
      pertaining to gene expression and associated growth conditions (even with very
      little knowledge of the associated regulatory mechanisms) is gathered from the
      literature and incorporated into RegulonDB, a database on transcriptional
      regulation and operon organization in E. coli. The link between growth
      conditions, signal transduction, and transcriptional regulation is modeled in the
      database in a simple format that highlights biological relevant information. As
      far as we know, there is no other database that explicitly clarifies the effect
      of environmental conditions on gene transcription. We discuss how this knowledge
      constitutes a benchmark that will impact future research aimed at integration of
      regulatory responses in the cell; for instance, analysis of microarrays,
      predicting culture behavior in biotechnological processes, and comprehension of
      dynamics of regulatory networks. This integrated knowledge will contribute to the
      future goal of modeling the behavior of E. coli as an entire cell. The RegulonDB
      database can be accessed on the web at the URL:
      http://www.cifn.unam.mx/Computational_Biology/regulondb/.

PMID- 14708115
TI  - Metabolic database systems for the analysis of genome-wide function.
AB  - Genome sequencing projects provide an inventory of molecular components for a
      wide variety of organisms. Metabolic databases integrate these functional
      descriptions of individual modules into a higher-level characterization of
      cellular metabolism. This article reviews efforts related to the development of
      metabolic databases and discusses how such systems have aided the delineation of
      genome properties. We illustrate the design features of metabolic databases and
      discuss the challenges facing metabolic as well as databases of other functional
      type.

PMID- 14708116
TI  - Exploiting evolutionary relationships for predicting protein structures.
AB  - In the last few years there have been many developments in computational biology,
      particularly with regard to novel, imaginative exploitation of genomic data.
      Disappointingly, there has been a lack of progress in the methodology for
      prediction of protein structures. In the last several years, however, promising
      new methods have finally begun to emerge. These methods are increasing the power
      and scope of the methodology, but, most importantly, they are generating new
      areas of investigation that we believe will accelerate progress in the field. In
      this review we describe recent developments and highlight the implications of
      their success as well as areas where efforts should be focused.

PMID- 14708117
TI  - Identifying constraints that govern cell behavior: a key to converting conceptual
      to computational models in biology?
AB  - Cells must abide by a number of constraints. The environmental constrains of
      cellular behavior and physicochemical limitations affect cellular processes. To
      regulate and adapt their functions, cells impose constraints on themselves.
      Enumerating, understanding, and applying these constraints leads to a constraints
      based modeling formalism that has been helpful in converting conceptual models to
      computational models in biology. The continued success of the constraints-based
      approach depends upon identification and incorporation of new constraints to more
      accurately define cellular capabilities. This review considers constraints in
      terms of environmental, physicochemical, and self-imposed regulatory and
      evolutionary constraints with the purpose of refining current constraints-based
      models of cell phenotype.

PMID- 14708118
TI  - Dynamical and integrative cell signaling: challenges for the new biology.
AB  - Years of careful experimental analysis have revealed that signaling molecules are
      organized into complex networks of biochemical reactions exquisitely regulated in
      time and space to provide a cell with high-fidelity information about an
      extremely noisy and volatile environment. A new view of signaling networks as
      systems consisting of multiple complex elements interacting in a multifarious
      fashion is emerging, a view that conflicts with the single-gene or protein
      centric approach common in biological research. The postgenomic era has brought
      about a different, network-centric methodology of analysis, suddenly forcing
      researchers toward the opposite extreme of complexity, where the networks being
      explored are, to a certain extent, intractable and uninterpretable. Both the
      cartoons of simple pathways and the very large "hair-ball" diagrams of large
      intracellular networks are also representations of static worlds, superficially
      devoid of dynamics and chemistry. These representations are often viewed as being
      analogous to stably linked computer and neural networks rather than dynamically
      changing networks of chemical interactions, where the notions of concentration,
      compartmentalization, and diffusion may be the primary determinants of
      connectivity. Arguably, the systems biology approach, relying on computational
      modeling coupled with various experimental techniques and methodologies, will be
      an essential component of analysis of the behavior of signal transduction
      pathways. Combining the dynamical view of rapidly evolving responses and the
      structural view arising from high-throughput analyses of the interacting species
      will be the best approach toward efforts toward greater understanding of
      intracellular signaling processes.

PMID- 14708119
TI  - The complexity of complexes in signal transduction.
AB  - Many activities of cells are controlled by cell-surface receptors, which in
      response to ligands, trigger intracellular signaling reactions that elicit
      cellular responses. A hallmark of these signaling reactions is the reversible
      nucleation of multicomponent complexes, which typically begin to assemble when
      ligand-receptor binding allows an enzyme, often a kinase, to create docking sites
      for signaling molecules through chemical modifications, such as tyrosine
      phosphorylation. One function of such docking sites is the co-localization of
      enzymes with their substrates, which can enhance both enzyme activity and
      specificity. The directed assembly of complexes can also influence the
      sensitivity of cellular responses to ligand-receptor binding kinetics and
      determine whether a cellular response is up- or downregulated in response to a
      ligand stimulus. The full functional implications of ligand-stimulated complex
      formation are difficult to discern intuitively. Complex formation is governed by
      conditional interactions among multivalent signaling molecules and influenced by
      quantitative properties of both the components in a system and the system itself.
      Even a simple list of the complexes that can potentially form in response to a
      ligand stimulus is problematic because of the number of ways signaling molecules
      can be modified and combined. Here, we review the role of multicomponent
      complexes in signal transduction and advocate the use of mathematical models that
      incorporate detail at the level of molecular domains to study this important
      aspect of cellular signaling.

PMID- 14708120
TI  - Maintaining data integrity in microarray data management.
AB  - Gene expression microarrays are a relatively new technology, dating back just a
      few years, yet they have already become a very widely used tool in biology, and
      have evolved to a wide range of applications well beyond their original design
      intent. However, while the use of microarrays has expanded, and the issues of
      performance optimization have been intensively studied, the fundamental issue of
      data integrity management has largely been ignored. Now that performance has
      improved so greatly, the shortcomings of data integrity control methods
      constitute a greater percent of the stumbling blocks for investigators.
      Microarray data are cumbersome, and the rule up to this point has mostly been one
      of hands-on transformations, leading to human errors which often have dramatic
      consequences. We show in this review that the time lost on such mistakes is
      enormous and dramatically affects results; therefore, mistakes should be
      mitigated in any way possible. We outline the scope of the data integrity issue,
      to survey some of the most common and dangerous data transformations, and their
      shortcomings. To illustrate, we review some case studies. We then look at the
      work done by the research community on this issue (which admittedly is meager up
      to this point). Some data integrity issues are always going to be difficult,
      while others will become easier-one of our goals is to expedite the use of
      integrity control methods. Finally, we present some preliminary guidelines and
      some specific approaches that we believe should be the focus of future research.

PMID- 14708121
TI  - Escherichia coli--a model system that benefits from and contributes to the
      evolution of proteomics.
AB  - The large body of knowledge about Escherichia coli makes it a useful model
      organism for the expression of heterologous proteins. Proteomic studies have
      helped to elucidate the complex cellular responses of E. coli and facilitated its
      use in a variety of biotechnology applications. Knowledge of basic cellular
      processes provides the means for better control of heterologous protein
      expression. Beyond such important applications, E. coli is an ideal organism for
      testing new analytical technologies because of the extensive knowledge base
      available about the organism. For example, improved technology for
      characterization of unknown proteins using mass spectrometry has made two
      dimensional electrophoresis (2DE) studies more useful and more rewarding, and
      much of the initial testing of novel protocols is based on well-studied samples
      derived from E. coli. These techniques have facilitated the construction of more
      accurate 2DE maps. In this review, we present work that led to the 2DE databases,
      including a new map based on tandem time-of-flight (TOF) mass spectrometry (MS);
      describe cellular responses relevant to biotechnology applications; and discuss
      some emerging proteomic techniques.

PMID- 14708122
TI  - A perspective of metabolic engineering strategies: moving up the systems
      hierarchy.
AB  - Metabolic engineering has been established as an important field in
      biotechnology. It involves the analysis, design, and alteration of the
      stoichiometric network using sophisticated mathematical and molecular biology
      techniques. It allows for improvement of pathway kinetics by removing flux
      bottlenecks, balancing precursors, and recycling cofactors used to increase
      product formation. The next step in the systems hierarchy is the constructive
      manipulation of regulatory networks. As our understanding of regulation continues
      to expand rapidly, engineering of intracellular regulation will become an
      integral aspect of metabolic engineering.

PMID- 14708123
TI  - Insights into the relation between mRNA and protein expression patterns: I.
      Theoretical considerations.
AB  - Translation is a central cellular process in every organism and understanding
      translation from the systems (genome-wide) perspective is very important for
      medical and biochemical engineering applications. Moreover, recent advances in
      cell-wide monitoring tools for both mRNA and protein levels have necessitated the
      development of such a model to identify parameters and conditions that influence
      the mapping between mRNA and protein expression. Experimental studies show a lack
      of correspondence between mRNA and protein expression profiles. In this study, we
      describe a mechanistic genome-wide model for translation that provides mapping
      between changes in mRNA levels and changes in protein levels. We use our model to
      study the system in detail and identify the key parameters that affect this
      mapping. Our results show that the correlation between mRNA and protein levels is
      a function of both the kinetic parameters and concentration of ribosomes at the
      reference state. In particular, changes in concentration of free and total
      ribosomes in response to a perturbation; changes in initiation and elongation
      kinetics due to competition for aminoacyl tRNAs; changes in termination kinetics;
      average changes in mRNA levels in response to the perturbation; and changes in
      protein stability are all important determinants of the mapping between mRNA and
      protein expression.

PMID- 14708124
TI  - Insights into the relation between mrna and protein expression patterns: II.
      Experimental observations in Escherichia coli.
AB  - There is a need for improved appreciation of the importance of genome-wide mRNA
      and protein expression measurements and their role in understanding translation
      and in relation to genome-wide mathematical frameworks for gene expression
      regulation. We investigated the use of a high-density microarray technique for
      mRNA expression analysis and a two-dimensional protein electrophoresis-tandem
      mass spectrometry method for protein analysis to monitor changes in gene
      expression. We applied these analytical tools in the context of an environmental
      perturbation of Escherichia coli cells-the addition of varying amounts of IPTG.
      We also tested the application of these tools to the study of a genetic
      perturbation of Escherichia coli cells-the ability of certain strains to
      hypersecrete the hemolysin protein. We observed a lack of correspondence between
      mRNA and protein expression profiles. Although our data do not include
      measurements on all expressed genes (because the ability to measure protein
      expression profiles is limiting), we observed that the qualitative and
      quantitative behavior of the measurements of a subset of expressed genes is
      similar to the behavior of the entire system. The change in observed average mRNA
      and protein amplification factors for 77 and 52 genes coincided with the observed
      change in mRNA amplification factor for the entire system. Furthermore, we found
      that the use of relative changes in expression could be used to elucidate
      mechanisms of gene expression regulation for the system studied, even when
      measurements were made on a small subset of the system.

PMID- 14708125
TI  - Transcriptional analysis of product-concentration driven changes in cellular
      programs of recombinant Clostridium acetobutylicumstrains.
AB  - Antisense RNA (asRNA) downregulation alters protein expression without changing
      the regulation of gene expression. Downregulation of primary metabolic enzymes
      possibly combined with overexpression of other metabolic enzymes may result in
      profound changes in product formation, and this may alter the large-scale
      transcriptional program of the cells. DNA-array based large-scale transcriptional
      analysis has the potential to elucidate factors that control cellular fluxes even
      in the absence of proteome data. These themes are explored in the study of large
      scale transcriptional analysis programs and the in vivo primary-metabolism fluxes
      of several related recombinant C. acetobutylicum strains: C. acetobutylicum ATCC
      824(pSOS95del) (plasmid control; produces high levels of butanol snd acetone),
      824(pCTFB1AS) (expresses antisense RNA against CoA transferase (ctfb1-asRNA);
      produces very low levels of butanol and acetone), and 824(pAADB1) (expresses
      ctfb1-asRNA and the alcohol-aldehyde dahydrogenase gene (aad); produce high
      alcohol and low acetone levels). DNA-array based transcriptional analysis
      revealed that the large changes in product concentrations (snd notably butanol
      concentration) due to ctfb1-asRNA expression alone and in combination with aad
      overexpression resulted in dramatic changes of the cellular transcriptome.
      Cluster analysis and gene expression patterns of established and putative operons
      involved in stress response, motility, sporulation, and fatty-acid biosynthesis
      indicate that these simple genetic changes dramatically alter the cellular
      programs of C. acetobutylicum. Comparison of gene expression and flux analysis
      data may point to possible flux-controling steps and suggest unknown regulatory
      mechanisms.

PMID- 14708127
TI  - Theoretical and computational studies of the glucose signaling pathways in yeast
      using global gene expression data.
AB  - We have combined DNA microarray experiments with novel computational methods as a
      means of defining the topology of a biological signal transduction pathway. By
      DNA microarray techniques, we previously acquired data on expression over time of
      all genes in the yeast Saccharomyces following addition of glucose to wild-type
      cells and to cells mutated in one or more components of the Ras signaling
      network. In addition, we examined the time course of expression following
      activation of components of the Ras signaling network in the absence of glucose
      addition. In this current study, we have applied a novel theoretical and
      computational framework to these data to identify the network topology of the
      glucose signaling pathway in yeast and the role of Ras components in that
      network. The computational approach involves clustering genes by expression
      pattern, postulating a signaling network topology superstructure that includes
      all possible component interconnections and then evaluating the feasibility of
      the superstructure interconnections by optimization methods using Mixed Integer
      Linear Programming techniques. This approach is the first rigorous mathematical
      framework for addressing the biological network topology issue, and the novel
      formulation features the introduction of discrete variables for the connectivity
      and logical expressions that connect the experimental observations to the network
      structure. This analysis yields a topology for the glucose signaling pathway that
      is consistent with, and an extension of, known biological interactions in glucose
      signaling.

PMID- 14708126
TI  - Prediction of transcriptional profiles of Synechocystis PCC6803 by dynamic
      autoregressive modeling of DNA microarray data.
AB  - Time-series profiles of gene expression generated by DNA microarrays possess
      sufficient information for building dynamic models of transcriptional behavior.
      This, however, requires properly designed experiments and sufficient independent
      data to validate such models. Here we report the use of AutoRegressive with
      eXogenous input (ARX) models to fit dynamic gene expression data obtained by
      subjecting cultures of the photosynthetic bacterium Synechocystis PCC6803 to
      consecutive light-to-dark transitions. Autoregressive with exogenous input models
      of appropriate complexity were selected by applying Akaike's information
      criterion (AIC) such as to maximize agreement between model predictions with
      experimental data without overfitting. These models were subsequently used to
      design the experimental profile of an optimal validating data set. Predictions
      from these models were tested in a second experiment and were found to match well
      with the validation data. Additionally, the models with the least error in
      predicting the expression profiles of the validation data set exactly match the
      model complexity predicted by AIC. Such models offer insights into cellular
      responses to environmental conditions and form the basis for hypothesizing and
      quantifying relationships that are presently poorly understood at the level of
      fundamental mechanisms.

PMID- 14708128
TI  - Exploring the overproduction of amino acids using the bilevel optimization
      framework OptKnock.
AB  - In this study, we modify and extend the bilevel optimization framework OptKnock
      for identifying gene knockout strategies in the Escherichia coli metabolic
      network, leading to the overproduction of representative amino acids and key
      precursors for all five families. These strategies span not only the central
      metabolic network genes but also the amino acid biosynthetic and degradation
      pathways. In addition to gene deletions, the transport rates of carbon dioxide,
      ammonia, and oxygen, as well as the secretion pathways for key metabolites, are
      introduced as optimization variables in the framework. Computational results
      demonstrate the importance of manipulating energy-producing/consuming pathways,
      controlling the uptake of nitrogen and oxygen, and blocking the secretion
      pathways of key competing metabolites. The identified pathway modifications
      include not only straightforward elimination of competing reactions but also a
      number of nonintuitive knockouts quite distant from the amino acid-producing
      pathways. Specifically, OptKnock suggests three reactions (i.e., pyruvate kinase,
      phosphotransacetylase, and ATPase) for deletion, in addition to the
      straightforward elimination of 2-ketoglutarate dehydrogenase, to generate a
      glutamate-overproducing mutant. Similarly, phosphofructokinase and ATPase are
      identified as promising knockout targets to complement the removal of pyruvate
      formate lyase and pyruvate dehydrogenase for enhancing the yield of alanine.
      Although OptKnock in its present form does not consider regulatory constraints,
      it does provide useful suggestions largely in agreement with existing practices
      and, more importantly, introduces a framework for incorporating additional
      modeling refinements as they become available.

PMID- 14708129
TI  - Early Alzheimer's disease.

PMID- 14708130
TI  - Early Alzheimer's disease.

PMID- 14708131
TI  - Early Alzheimer's disease.

PMID- 14708132
TI  - Early Alzheimer's disease.

PMID- 14708133
TI  - Suspected pulmonary embolism.

PMID- 14708134
TI  - Suspected pulmonary embolism.

PMID- 14708135
TI  - Counting whales in the North Atlantic.

PMID- 14708136
TI  - Traumatic lumbar punctures.

PMID- 14708137
TI  - Oversight, overlap, or not immediately relevant?

PMID- 14708138
TI  - Best evidence in anesthetic practice: prevention: magnesium sulfate reduces the
      risk of eclampsia in women with pre-eclampsia.

PMID- 14708139
TI  - What stories should GPs be telling?

PMID- 14708140
TI  - Corridor teaching.

PMID- 14708141
TI  - The development of family health nurses and family nurse practitioners.

PMID- 14708142
TI  - Marine envenomations. Part 1--Jellyfish.
AB  - BACKGROUND: Many venomous marine creatures inhabit Australian waters, causing
      significant morbidity and occasional fatalities. Part 1 of this article looks at
      jellyfish envenomations, an important overall cause of marine injuries.
      OBJECTIVE: To discuss the features of envenomation by some of the more commonly
      encountered jellyfish of medical significance, and the recommended first aid and
      medical management of such envenomations. DISCUSSION: It is intended that the
      information contained in this article will be informative to general
      practitioners dealing with jellyfish stings throughout Australia. Much of what we
      know has come from the astute observations of GPs in tropical Australia. However,
      there remains a lot to be learnt about jellyfish envenomation.

PMID- 14708143
TI  - Marine envenomations. Part 2--Other marine envenomations.
AB  - BACKGROUND: Australian waters contain a variety of venomous creatures, including
      jellyfish, stinging fish, blue-ringed octopus, sea snakes, cone snails and
      stingrays. OBJECTIVE: Part 2 of this article focusses on common marine
      envenomations other than jellyfish stings. DISCUSSION: Even though mortality from
      these envenomations is low, there is a high level of morbidity especially with
      stonefish and other stinging fish envenomations. Some envenomations, however, are
      serious enough to require antivenom treatment and deaths still occasionally
      occur.

PMID- 14708144
TI  - Sexual health for travellers.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are prevalent worldwide, yet a
      high proportion of international travellers engage in unprotected sex while
      overseas and may be at risk. OBJECTIVE: This article discusses some of the STIs
      that may be acquired abroad, and suggests key points of pretravel advice for the
      general practitioner to give the traveller before departure. DISCUSSION: Many
      travellers will visit their GP for pretravel vaccinations and advice. This
      presents an ideal opportunity for pretravel sexual health education and
      discussion on the risks and prevention of HIV and other STIs.

PMID- 14708145
TI  - Bushfires, 2003. A rural GP's perspective.
AB  - BACKGROUND: Extensive bushfires in January and February of 2003 had a major
      impact on many communities in northeast Victoria, East Gippsland, southern New
      South Wales and Canberra. These fires eventually engulfed an area roughly
      equivalent to the entire area of Germany. OBJECTIVE: This article describes the
      impact of the fires and the role of the general practitioner in the emergency
      response, and presents recommendations for the role of general practice in future
      disaster planning. DISCUSSION: General practitioners have critical roles in the
      provision of round the clock general medical services to their communities in
      times of bushfire or natural disaster. They also act as gatekeepers to mental
      health services, psychiatric referral and counselling alongside other community
      based programs. Divisions of general practice have a pivotal role to play in
      disaster plans, particularly in coordinating the maintenance of ongoing medical
      services, facilitating communication between GPs and essential services, and
      integrating general practice into postdisaster recovery.

PMID- 14708146
TI  - Drowning management and prevention.
AB  - BACKGROUND: Accidental drowning causes over 300 deaths annually in Australia, and
      many more instances of 'near drowning'. OBJECTIVE: This article outlines the
      management of near drowning and the general practitioner's role in drowning
      prevention. DISCUSSION: Cardiopulmonary resuscitation (CPR) is the mainstay of
      immediate management. Continuing CPR for 30 minutes if necessary is appropriate,
      particularly in hypothermic patients. Patients who have been successfully
      resuscitated and those with clinical features suggesting aspiration should be
      given 100% oxygen and transferred to hospital. Drowning prevention is a
      significant public health issue, and the GP's role in education and support of
      rescue services and public awareness campaigns is important.

PMID- 14708147
TI  - Monitoring: to infinity and beyond!
AB  - BACKGROUND: For many patients, the initial prescription is only the beginning of
      the prescribing process, with the prescription needing to be repeated, sometimes
      for the life of the patient. OBJECTIVE: This article discusses the factors to
      consider when reviewing a patient for a repeat prescription and some approaches
      to long term pharmacotherapy. DISCUSSION: When writing repeat prescriptions it is
      important to take time to consider the physiological changes of aging, emergence
      of new contraindications in the patient, emergence of new evidence regarding drug
      therapy, and whether it is appropriate to consider drug withdrawal. The role of
      the pharmacist in the prescribing process, particularly in performing home
      medicine reviews, is also briefly discussed.

PMID- 14708148
TI  - Referral of patients with depression to specialist psychological care from
      general practice.

PMID- 14708149
TI  - Medication errors--warfarin.

PMID- 14708150
TI  - Burning feet syndrome. A clinical review.
AB  - BACKGROUND: Burning pain in the feet has been known to occur as a distinct
      clinical symptom for almost two centuries. Despite being a common and fascinating
      clinical entity, this syndrome has received scant attention in the medical
      literature and has been described only in anecdotal reports. OBJECTIVE: This
      article describes and discusses the various aspects of this intriguing syndrome.
      DISCUSSION: Burning feet syndrome (BFS) is a common disorder especially among the
      elderly and is frequently encountered in general practice. There is no specific
      aetiology and it can occur as an isolated symptom or as part of a symptom complex
      in a variety of clinical settings. In contrast to the presence of distressing
      subjective symptoms, the physical examination is marked by a paucity of objective
      signs. The pathophysiology of BFS is not very clear and treatment varies
      depending on the aetiology.

PMID- 14708151
TI  - Predictive value: will I need insulin?

PMID- 14708152
TI  - The decision to enter general practice.

PMID- 14708153
TI  - Sudden onset double vision. Eye series--11.

PMID- 14708155
TI  - Intellect: if we don't use it do we lose it?

PMID- 14708154
TI  - Systemic or topical treatment for impetigo?

PMID- 14708156
TI  - Rethinking general practice for the 21st century. The patient counts!
AB  - BACKGROUND: Increasingly, reforms to health care systems appear to interfere with
      the traditional (healer) role of the general practitioner, and are perceived to
      disrupt patient care and the therapeutic relationship. OBJECTIVE: To outline
      measures for the survival and future development of the discipline of general
      practice in Australia. DISCUSSION: In order to preserve longitudinal relationship
      centred care and high level primary care clinical expertise, health bureaucracies
      and general practice itself, must re-focus care on the individual and community,
      integrating new developments rather than allowing 'new ideas and system
      pressures' to continually distort functional general practice.

PMID- 14708157
TI  - Expanding medical education in general practice.

PMID- 14708158
TI  - Closing the gap and widening the scope. New directions for research capacity
      building in primary health care.
AB  - BACKGROUND: Research capacity building initiatives abound within primary health
      care to increase the research base of the many component health professionals and
      organisations. Most initiatives aim to close the gaps between research, policy
      and practice. Many of these approaches have been unable to build the necessary
      skills among primary health care researchers to fully integrate research evidence
      into clinical practice, and ultimately to inform policy in this complex arena.
      OBJECTIVE: To propose a paradigm shift in the content of capacity building as a
      step toward closing the gaps between research, policy and practice. DISCUSSION:
      The complexity of the primary health care environment and the concept of
      development as a means to understanding and operating within primary health care
      research, policy and practice environments is discussed. A small pilot study was
      used to identify the underlying skills required in research, evaluation and
      development. In order to facilitate the paradigm shift an organisational
      development model was utilised that demonstrated congruency with this skill set.
      Further research is required to validate and apply this model in a primary health
      care research capacity building context.

PMID- 14708159
TI  - Is low immunisation coverage in inner urban areas of Australia due to low uptake
      or poor notification?
AB  - INTRODUCTION: The Australian Childhood Immunisation Register (ACIR) consistently
      reveals pockets of lower immunisation coverage in inner urban areas. We
      investigated whether low uptake or poor notification of immunisation is the main
      reason for this difference. METHODS: We estimated under reporting by telephone
      surveying the parents of 640 children recorded as incompletely immunised on the
      ACIR at 12 months of age. Immunisation status was based on parental report of
      written records and/or date of receipt. RESULTS: Of the 97 children living in
      inner urban areas (defined by postcode and population density), 55 (57%) were
      shown to be 'definitely immunised'. One hundred and thirty-four (53%) of the 253
      children in other urban areas were shown to be 'definitely immunised'. Both these
      groups were significantly more likely to be 'definitely immunised' than the 104
      (36%) of 290 children in areas outside capital cities (p < 0.0001). DISCUSSION:
      Apparent lower immunisation uptake in inner urban areas of Australia may be
      attributable to reporting error.

PMID- 14708160
TI  - Does external support from divisions increase preventive activities in rural
      Australian general practice?

PMID- 14708161
TI  - [Determination of individually endurable intraocular pressure (pressure of
      target) in primary glaucoma].
AB  - On the basis of ocular perfusion pressure a new method was suggested for
      determining an individually endurable intraocular pressure (IOP), i.e. pressure
      of target. A total of 390 eyes (232 patients with primary open-angle and normal
      tension glaucoma) were examined before and after conservative and surgical
      treatment. The pressure of target was found, in a progressing worsening of visual
      functions, to be significantly lower versus the stabilized glaucoma, which was
      due to a low ocular perfusion pressure. The maximally tolerable IOP in a
      progressing glaucomatous optic neuropathy concomitant with a normalized IOP
      amounts to 13-15 mm Hg; while, in the stabilized glaucoma it can exceed the mean
      statistic norm. The pressure of target was shown to be a non-permanent value,
      which changes depending on the dynamics of the ophthalmic perfusion pressure and
      IOP. The sensitivity of the suggested method is 77.4%. It can be used in
      prognosticating the glaucomatous-process clinical course and in choosing an
      optimal tactics for the treatment of open-angle and normal-tension glaucoma.

PMID- 14708162
TI  - [Glaucomatous neuropathy concomitant with carotid pathology: the specificity of
      pathogenesis and diagnostics].
AB  - The below clinical peculiarities of glaucomatous optic neuropathy (GON) were
      defined in carotid lesions: saucer-shaped excavation of the optic nerve disk,
      local or total loss of the retinal ring, peripapillary chorioretinal atrophy as
      well as central defects and segmental prolapses in the visual field. Fluorescence
      angiography was used to determine the regions of local disk ischemia. Ultrasound
      scanning of eye vessels provide for detecting the impaired blood circulation in
      the ocular artery and in the central retinal artery, i.e. a pronounced lower
      terminal diastolic velocity of blood flow and a higher resistance index.

PMID- 14708163
TI  - [Intraoperative diagnosis of retinal ruptures in rhegmatogenous retinal
      detachment in avitreous eyes by using a coloring agent].
AB  - Sixteen patients were operated for regmatogene retinal detachment developed at
      different time periods after a previously made vitrectomy; no retinal ruptures
      were found in preoperative examinations. The method of colouring with subretinal
      fluid, 0.1% fluorescence solution, was intraoperatively used for the detection of
      such ruptures. The coloured fluid escaped from the subretinal cavity through a
      retinal rapture into the vitreal cavity, which ensured an easy visualization of
      ruptures. Retinal ruptures could be detected in all 16 (100%) patients. They were
      located in 8 (50%) cases in the zone of previously made sclerotomy and were
      regarded as an outcome of the local proliferative vitreoretinopathy on the
      remains of the basic vitreous elements.

PMID- 14708164
TI  - [Place of the transplantation of the amniotic membrane in the treatment of
      corneal diseases concomitant with corneal neovascularization].
AB  - Published data and authors' independent observations related with the influence
      produced by the transplantation of the amniotic sac on corneal neovascularization
      are described. The epithelial-and-stromal corneal defect as well as the limbic
      epithelium deficit with a subsequent conjunctivization of the corneal epithelium
      and corneal neovascularization are one of the key mechanisms of corneal
      neovascularization. The amniotic sac transplantation, made for the purpose of
      reconstructing the eye surface, ensures the conditions for a fast recovery of the
      corneal epithelium and, thus, prevent the corneal neovascularization. The surgery
      can be recommended as an effective treatment technique applicable to corneal
      pathologies concomitant with the limbic epithelium deficit, persistent epithelial
      and-stromal corneal defect and with the corneal neovascularization.

PMID- 14708165
TI  - [Use of instenon in complex treatment of patients with optic nerve atrophy caused
      by craniocerebral trauma].
AB  - Instenon, a combined nootropic agent, was used on the step-type basis within a
      complex treatment of optic nerve atrophy caused by craniocerebral trauma. Our
      study revealed that instenon, when used within a complex treatment of a partial
      optic nerve atrophy caused by craniocerebral trauma, improved the visual acuity
      in 85.7% of patients and it expanded the total visual field in 76.2% of patients,
      whereas the routine therapy ensured the related improvements in 58.9% and 61.5%
      of patients, respectively. Besides, the drug provided for a better retinal
      electric sensitivity and for a better optic nerve conduction in 73.8% of cases
      versus 64.1% of cases with basic therapy. Increased velocity parameters in the
      ocular-artery blood flow were registered in 77.1%, of patients who received
      instenon, by duplex scanning.

PMID- 14708166
TI  - [Choice of a surgical correction method in hypermetropic anisotropia in
      children].
AB  - The results of surgical techniques applicable to hypermetropia correction, i.e.
      lamellar keratotomy (LK), lamellar keratotomy with thermal keratocoagulation
      (LKTKC) and sub-flap photokeratectomy (LASIK), in 80 children, aged 6 to 14, with
      hypermetropia ranging from 3.5 to 9.5 diopters and with astigmatism ranging from
      0.75 to 2.75 diopters are analyzed. The follow-up varied from 1 to 3 years. LASIK
      (reduction of astigmatism by 1.61 +/- 0.43 diopters or 78%) was proven to be an
      optimal method in the correction of astigmatic hypermetropic anisometropia. LASIK
      (reduction of anisometropia by 3.44 +/- 0.44 diopters or 80%) is preferable in
      the correction of a spherical hypermetropic anisometropia of up to 3.0 diopters
      inclusively; the LK method (an improvement of clinical refraction by 4.37 +/-
      0.87 diopters) is effective in anisometropia of 3.0 to 5.5 diopters; and LKTKC is
      effective in anisometropia of 5.5 to 7.5 diopters. The latter ensures an
      improvement of the corneal refraction by more than 2 diopters (2.15 +/- 0.44
      diopters) versus LK. TKC is possible as a single-stage procedure made in the
      remote time period. LASIK is more preferable in astigmatism of more than 1.5
      diopters.

PMID- 14708167
TI  - [Effects of ozone therapy on the functional activity of the retina in patients
      with involutional central chorioretinal dystrophy].
AB  - The retinal electrogenesis was studied in central chorioretinal dystrophy (CCRD)
      of different stages. The general peculiarities of the ozone-therapy influence on
      the functional retinal activity typical of any CCRD stage were detected; they
      comprise: an increasing activity of neurons in the muscular region and a
      specificity related with the dynamic functional activity of the retinal
      peripheral segments peculiar of each disease stage. A sharp growth of glial index
      Cg (b/R12) detected in all patients is indicative of an activated metabolism of
      Mueller glial cells and of impaired glial-neuron relations in the retina as
      observed in CCRD. A decreasing Cg, observed after ozone-therapy, is an indirect
      confirmation of anti-hypoxic effect produced by ozone, which can be regarded as a
      patho-physiological mechanism of its positive influence on the dynamics of the
      functional retinal activity. Ozone-therapy is recommended to be implemented with
      the electroretinography monitoring.

PMID- 14708168
TI  - [Importance of studying the accommodation function in the diagnosis of clinical
      forms of hypermetropia].
AB  - Two hundred and thirty-one patients, aged 6 to 18, with hypermetropia were
      examined. They were shared between two groups with respect to an accommodation
      state: group 1--patients with weak accommodation, group 2--patients with normal
      accommodation. The below ocular parameters were registered for groups 1 and 2,
      respectively: axial size--22.35 mm and 21.58 mm, corneal diameter--11.48 mm and
      10.74 mm, scleral ring diameter in the projection of the scleral central portion-
      14.66 mm and 13.98 mm, ocular refracting power--59.79 d and 62.23 d, corneal
      refraction--41.85 d and 42.82 d, and lens refraction--22.05 d and 24.03 d. New
      clinical signs were specified for uncomplicated type of congenital hypermetropia.
      The parameters of patients with normal-accommodation hypermetropia are typical of
      axial hypermetropia in adults due to growth inhibition, while the parameters of
      patients with weakened accommodation are typical of optical hypermetropia as a
      variation of normal eye development.

PMID- 14708169
TI  - [Study of the surface tear tension and evaluation of its importance for the
      retinal physiology and pathology in contact correction and in adaptation to soft
      contact lenses].
AB  - The surface lachrymal-fluid (LF) tension was investigated by teardrop dissection
      in 115 patients with myopia before they were prescribed soft contact lenses
      (SCL). Such tension was found to be of clinical importance for the development of
      SCL adaptation disorders. A longer adaptation period in patients with myopia was
      associated with a low surface LF tension. A high surface LF tension concurrent
      with the teardrop dissection mode of the destruction type was typical of the
      pathological nature of SCL adaptation (12.1% of patients). The obtained data are
      needed to detect timely the risk of dysadaptation disorders and corneal
      complications before SCL prescription for the purpose of undertaking the
      pathogenetically substantiated medication to prevent such complications.

PMID- 14708170
TI  - [Coagulation activity of the lacrimal fluid and the concentration of glucose in
      it as a criterion of diagnosis and prognosis of early-stage diabetic
      retinopathy].
AB  - Fifty patients with insulin-dependent diabetes mellitus (DM) and with the disease
      record ranging from 6 months to 5 years and 30 virtually healthy persons were
      examined. The follow-up varied from 1.5 to 2 years. The obtained results were
      made use of to formulate the below diagnostic criterion: a simultaneous increase
      of the levels of the coagulation activity of the lachrymal fluid (LF) and of the
      glucose concentration in LF with at least one such phenomenon being registered in
      one eye and a total asymmetry of more than 0.75 are indicative of diabetic
      retinopathy or of the possibility it would develop. The mentioned diagnostic
      criterion can be applied for detecting the risk groups among the DM patients.

PMID- 14708171
TI  - [Laser-correlation spectroscopy of the lacrimal fluid in the evaluation of the
      semiotic nature of postoperative inflammatory reaction and the degree of its
      severity in patients with diabetes mellitus after intraocular lens implantation].
AB  - Lavages of the lacrimal fluid were examined, before operation and immediately
      after operation, in 47 patients with diabetes mellitus and with pseudophakia in
      order to define the possibilities of the method of laser-correlation spectroscopy
      (LCS) in evaluating the semiotic nature and a severity degree of postoperative
      inflammation. It was found that, when the subjective symptomatology of
      inflammation in the LCS spectrums intensified, there was a higher contribution to
      the light dissemination of particles with a hydrodynamic diameter of 600 nm and
      more (i.e. of heavy lipoprotein complexes and of immune complexes), which were
      determined after a computer-based processing as a condition of primary
      intoxication and of immune shifts. The LCS results objectively confirmed that the
      degree of inflammatory changes during the early postoperative period was reliably
      higher in patients with a level of glycolyzed hemoglobin exceeding 9% versus
      patients with the above parameter being below 9%.

PMID- 14708172
TI  - [Assessment of the efficiency of different formulae applied to calculating the
      optic power of an intraocular lens in trans-scleral fixation].
AB  - The paper is dedicated to assessing the efficiency of various formulae designed
      to calculate the IOL optic power, when IOL is fixed transscelerally in patients
      with an inconsistent ligament-capsular lens apparatus. According to an analysis
      of the obtained data, the closest values were ensured, as regards the practical
      result, with theoretical formulae, i.e. Binkhorst, Hoffer-Colenbrander and
      Binkhorst in situ. The postoperative refraction deviation was below 0.1 diopters,
      which is optimal for such calculation types. Should the use of theoretical
      formulae be problematic due to a lack of appropriate devices, then it is
      acceptable to apply the SRK-II empiric formula with a correction by -1.6 diopters
      to guarantee the postoperative emmetropia.

PMID- 14708173
TI  - [Clinical forms and treatment of keratitis caused by varicella-zoster virus].

PMID- 14708174
TI  - [Preparation polyosm in the treatment of glaucoma].

PMID- 14708175
TI  - [Peripheral vitreo-choroidal-retinal dystrophies in students of higher institutes
      of learning].

PMID- 14708176
TI  - [Analysis of complications in surgical interventions in traumas of the organ of
      vision].

PMID- 14708177
TI  - [Bilateral ischemic neuropathy].

PMID- 14708178
TI  - [Cases of herpetic and cytomegalovirus lesions of the eye].

PMID- 14708179
TI  - [Case of corneal actinomycosis].

PMID- 14708180
TI  - [A comparative description of using different-type explants in surgery of retinal
      detachment at the present stage].

PMID- 14708181
TI  - [Orbital complications in purulent-inflammatory diseases of paranasal sinuses:
      diagnosis and therapy].

PMID- 14708182
TI  - [Development of refraction in children].

PMID- 14708183
TI  - [S.G. Magil'nitskii -- an outstanding Russian historian in the field of
      ophthalmology (on the 100th anniversary of his birthday)].

PMID- 14708184
TI  - [Sources and evaluation of study methods in public health research].
AB  - The statistical sources available in Russia's healthcare and the potentialities
      of such sources for evaluating the general level of the population health were
      comparatively analyzed. The most informative sources were defined; additionally
      to the stable data of the medical-and-demographic nature and with due respect to
      the data of medical documents known by respondents integrated parameters of
      health were suggested, which are based on questionnaires and self-evaluation of
      health. The above methods of health investigation and evaluation accepted in the
      world practice ensure the comparability of data and a more active cooperation
      within joint healthcare projects.

PMID- 14708185
TI  - [Social risk factors and development of the vegetative dystonia syndrome in the
      puberty age children].
AB  - Population examinations of 634 children, aged 12 to 15, with the vegetative
      dystonia syndrome (VDS) made by means of questionnaires revealed high-risk
      factors of vegetative malfunctions, e.g. negative habitat-and-social impacts,
      specific features of the teenagers typical of the puberty age and harmful habits.
      It was concluded as necessary to undertake primary leveling schemes to eliminate
      the micro-medium aggressiveness in teenagers with VDS for the purpose of
      normalizing the compensation-and-adaptation apparatus and to use, subsequently,
      the regulatory effect of the above apparatus for recovering the functions of the
      internal organs and systems.

PMID- 14708186
TI  - [A medical-social description of and approaches to the prevention of
      musculoskeletal system diseases].
AB  - The epidemiological as well as medical-and-social aspects related with diseases
      of the musculoskeletal system as observed in the Saratov Region over the recent 7
      years are presented in the paper. A set of measures was worked out to optimize
      the medical-and-social aid rendered to patients with defects in the
      musculoskeletal system; the mentioned measures can be also used to advance the
      prevention system.

PMID- 14708187
TI  - [Alcohol and malignant neoplasm].
AB  - Trends observed in Belarus during 1970-1999 and related with mortality of
      different-type cancer, e.g. breast cancer in women, cancer of the mouth, pharynx,
      esophagus and stomach, were analyzed versus trends related with the per-capita
      consumption of various beverages by using the time-series analysis. The results
      reveal a positive and statistically significant effect of the per-capita vodka
      consumption on the cancer mortality rate. According to the analysis, a 1%
      increase in the per-capita vodka consumption entails a 0.58% growth in the breast
      cancer mortality rate and a 0.66% growth in the esophagus cancer mortality rate.
      The case study is another solid proof to the fact that a substantial share of
      breast cancers and of esophageal cancers are brought about by strong beverages.

PMID- 14708188
TI  - [Private sector health services use in the Omsk region].
AB  - The progress made by the private medical sector in different Russia's regions has
      been uneven. A key share of private medical facilities is concentrated in big
      cities. The frequency rate of citizens' asking the rural and urban private
      practitioners for medical care was investigated by the example of the Omsk
      Region. The dynamic morbidity and the specificity of its structure are described
      on the basis of the data contained in basic medical registration documents
      borrowed from private medical institutions. The importance and value of the
      information-and-analytical cooperation between the private-sector structures, on
      the one hand, and the healthcare management bodies, on the other hand, are
      pointed out.

PMID- 14708189
TI  - [Planning of patient care facilities as a basic component of municipal demand].

PMID- 14708190
TI  - [Medical-social marketing and optimization of multi-profile hospital activity].

PMID- 14708191
TI  - [The importance of new remuneration forms in the process of reforming a district
      health care system].
AB  - An experience of reforming the healthcare system in the Saratov Region is
      outlined in the paper. The reforms are based primarily on the following: a system
      of stimulating payments; a contract-based structure of labor management and of
      remuneration; quality monitoring of medical services; and resource-sparing
      technologies.

PMID- 14708192
TI  - [Preventive services at urban pediatric clinics].
AB  - The authors analyzed and assessed the actual state-of-art related with the
      preventive activities undertaken by pediatric clinics. It was established that
      the practitioners, medical personnel and parents were poorly informed on the
      issues pertaining to the development and education of small and pre-school
      children. The actual preventive-aid measures, now available at pediatric clinics,
      and their real value were found to make 25-30% of the total activity of a
      district pediatrician. A quality evaluation coefficient applicable to prevention
      was elaborated and introduced into the operation of pediatric clinics. The
      coefficient is calculated with respect to the value of its separate components
      and it is target at the final result in the activity of the pediatrician and of
      the pediatric service as a whole, which is child's health. It was calculated for
      all decreed ages from birth to the age of 6. Its maximum values were registered
      at an age of 3 months (0.62), 1.5 years (0.61) and of 4 years (0.64). The data
      are processed by a special soft with a final coefficient value being determined:
      0.9-1.0--splendid, 0.75-0.89--goo, 0.65-0.74--satisfactory, 0.64 and less-
      unsatisfactory. The above method made it possible to promote and expand the
      preventive activity in case of each children's age.

PMID- 14708194
TI  - [State-of-the-art and outlooks for the development of video-endo-surgery in the
      Leningrad region].

PMID- 14708193
TI  - [Development of telemedicine in country's remote regions].

PMID- 14708195
TI  - [Management and results of the clinical-anatomical sector in Saint-Petersburg].
AB  - A standard of diagnostics, namely, of divergence or coincidence (in %) between
      the clinical and the postmortem diagnoses as well as a category of such
      divergence (diagnostic error) is of primary importance within the system of final
      criteria-based evaluations of the medical care. City Morbid Anatomy Bureau (CMAB)
      was set up, 1989, in Saint Petersburg in order to coordinate the clinical and
      pathologoanatomic functions as well as to shape the unified approaches and to
      ensure equal opportunities of obtaining the unified information from all city
      patient-care facilities. A unified and formalized card, i.e. "card of the
      diseased", is filled in for all dead who were examined by the pathologist. The
      data, when processed by a special program, can be used to derive statistics on
      the mortality structure (in hospitals, at home, and in separate patient-care
      facilities), on complications (immediate death causes), as well as on a presence
      and nature of diagnostic errors (in different patient-care facilities, in cases
      of various nosological forms, and for certain age-and-sex categories etc.). This,
      in its turn, can be used to draw the annual reports for the city and, if
      necessary (e.g. upon a request from a medical institution), to compose the
      analytic reports. Finally, the paper contains the nosological structure of those
      who died in and outside the urban hospitals; there is also a dynamic analysis of
      the nature and reasons of diagnostic errors.

PMID- 14708196
TI  - [Management of the activity of a preventive and treatment facility].

PMID- 14708197
TI  - [The forms of securing the patients' rights in the legislation of European
      countries].

PMID- 14708198
TI  - [On a new All-Russia program of teaching the history of medicine].

PMID- 14708199
TI  - [Health care management in Russia in the second half of the 19th century].

PMID- 14708200
TI  - [Medical intellectuals in social class hierarchy of the Russian Empire in the
      19th century].

PMID- 14708201
TI  - [Establishment of the Zemstvo Sanitary Service in the Penza Province].

PMID- 14708203
TI  - [Medicine in the Zaporozhskaia Sech].

PMID- 14708202
TI  - [From the history of the Peter-the-Great Hospital (on the occasion of the 100th
      anniversary of its foundation)].

PMID- 14708204
TI  - [Searching for an unknown physician-in-ordinary].

PMID- 14708205
TI  - [Joseph-Frederic-Benoit Charriere: on the occasion of his 200th birthday
      anniversary].

PMID- 14708206
TI  - [The foreground for the establishment of medical societies in Siberia].

PMID- 14708207
TI  - [Three patients with weight loss as a result of sarcoidosis presenting as liver
      disease].
AB  - Sarcoidosis presenting as a liver disease is uncommon. Hepatic sarcoidosis was
      diagnosed in three male patients aged 80, 64 and 69 years. They all presented
      with aspecific symptoms such as weight loss. Further investigation revealed liver
      disease, and liver biopsies demonstrated the presence of non-caseating
      granulomas. However, non-caseating granulomas can be associated with a great
      number of disorders and are therefore not specific. Other causes were excluded
      before the diagnosis of hepatic sarcoidosis was established with reasonable
      certainty. The diagnosis was finally confirmed on the basis of medical history,
      laboratory tests and histology. Sarcoidosis presenting as symptomatic liver
      disease can be treated with corticosteroids and probably with ursodeoxycholic
      acid as well. These three patients were treated with corticosteroids. The first
      patient died a year later from a cerebral infarct, the second one after a few
      months from a (non-sarcoidotic) cerebral haemorrhage and the third one after
      eight years from hepatic failure.

PMID- 14708208
TI  - [Beta-blocking drugs indicated in patients with heart failure].
AB  - Until recently, beta-blocking drugs were considered to be contraindicated in
      patients with chronic heart failure. However, several well-conducted randomised
      clinical trials have now proven otherwise. Yet, it was still not clear whether
      nonselective alpha-, beta 1- and beta 2-receptor blockade with carvedilol would
      be superior to selective beta 1-receptor blockade with metoprolol. One of the
      studies ('Carvedilol or metoprolol European trial' (COMET)) demonstrated a
      statistically significant 17% reduction of all-cause mortality with carvedilol.
      Although striking, the results may have been influenced by differences in blood
      pressure and heart rate, as well as the short-acting formula of metoprolol that
      was used. Furthermore, the 'Carvedilol hibernation reversible ischaemia trial;
      marker of success' (CHRISTMAS) study demonstrated myocardial hibernation in the
      majority of ischaemic heart-failure patients, and showed beneficial effects on
      left-ventricle function with carvedilol in both hibernated and non-hibernated
      patients. Despite this and the rest of the overwhelming evidence, at present only
      a minority of eligible chronic heart-failure patients are treated with beta
      blockers.

PMID- 14708209
TI  - ['Knowledge Infrastructure for Public Health': an advisory report from the
      Advisory Council on Health Research].
AB  - Social, scientific and technological developments are forcing health care systems
      to shift the focus from disease to health and from cure to prevention. The
      Advisory Council on Health Research (RGO) has published an advisory report about
      the knowledge infrastructure serving the needs of public health in the
      Netherlands. The Council's concept of public health also includes aspects such as
      policy and health management. The Council concludes that more research is needed
      on the following determinants of health: environmental issues, social factors,
      unhealthy behaviour and genetic factors. Intervention research must focus on
      health protection, health promotion and disease prevention. The public health
      infrastructure can be improved by amalgamating research groups, establishing
      departments of public health at every academic medical centre, and linking
      service, education and research.

PMID- 14708210
TI  - [The role of intercellular communication via "gap junctions" in disease].
AB  - Gap junctional intercellular communication plays an important role in the
      maintenance of cellular homeostasis. The flow of chemical messengers through gap
      junctions, gap junctional intercellular communication, is essential in processes
      such as electrical coupling, embryonic development and adaptive tissue response.
      Gap junctions are formed by connexin proteins. Mutational alterations in the
      connexin genes are associated with the occurrence of multiple diseases, such as
      peripheral neuropathy, cardiovascular disease, dermatological disease, hereditary
      deafness and cataract. Consequently, modulation of gap junctional intercellular
      communication is a potential pharmacological target. Future research, based, for
      example, on the recent developments in genetics, may clarify gap junction
      physiology. This will in turn provide promising perspectives for the development
      of targeted drugs.

PMID- 14708211
TI  - [Diastolic heart failure].
AB  - Diastolic heart failure is predominantly a disease of the elderly: at the age of
      70 years, almost half of all patients with heart failure have diastolic heart
      failure. Hypertension and obesity are common underlying disorders in patients
      with diastolic heart failure. Patients with diastolic heart failure have an
      equal, or only slightly better, prognosis in terms of mortality compared to
      patients with systolic heart failure. Echocardiography can distinguish diastolic
      heart failure from systolic heart failure. Patients with heart failure and a
      normal ejection fraction almost certainly have a diastolic dysfunction. There is
      a lack of reliable data about the optimal medicinal treatment strategy for
      patients with diastolic heart failure. Angiotensin-converting enzyme (ACE)
      inhibitors, beta-blockers, and (non-dihydropyridine) calcium antagonists have
      therapeutic potential. Digoxin may be contraindicated.

PMID- 14708212
TI  - [Drug treatment of gastro-esophageal reflux disease in pregnant women: consensus
      guidelines of gastroenterologists and gynaecologists].
AB  - Lifestyle changes are recommended as the first step in the treatment of pregnant
      women with heartburn. If symptoms persist, antacids or the mucoprotective
      sucralfate can be prescribed. If symptoms are persistent and severe, acid
      secretion inhibitors may be prescribed; the proton-pump inhibitor omeprazole is
      the drug of choice. It is unlikely that this drug could harm the fetus but the
      possibility cannot be entirely excluded. Prescription should be delayed until
      after the first trimester, whenever possible. Patients who have become pregnant
      while using these drugs can be reassured.

PMID- 14708213
TI  - [From gene to disease; E-cadherin and hereditary diffuse gastric cancer].
AB  - Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome
      associated with an early-onset, histologically diffuse, signet ring cell type
      gastric cancer and the occurrence of cancer at other anatomical sites, i.e.
      breast, colon, prostate and ovary. Inactivating germline mutations in the CDH1
      gene, encoding the cell to cell adhesion protein E-cadherin, predispose to HDGC.
      About 30% of HDGC families have a proven pathogenic CDH1 mutation. Lifetime
      penetrance of HDGC is about 70%. In HDGC families the recommendation for
      prophylactic total gastrectomy is restricted to carriers of an inactivating CDH1
      mutation.

PMID- 14708214
TI  - [Diagnostic images (169). A toddler not feeling well and having a rash. Eczema
      herpeticum].
AB  - A 1-year-old boy with eczema presented with fever and a rash, which was diagnosed
      as eczema herpeticum.

PMID- 14708215
TI  - [Terminal sedation in mentally competent patients: no overriding medical-ethical
      arguments against in the medical literature].
AB  - OBJECTIVE: To collect medical-ethical arguments for and against the practice of
      terminal sedation in mentally-competent patients. DESIGN: Literature search.
      METHOD: Medical-ethical arguments for and against the practice of terminal
      sedation were sought in electronic databases, for example Pubmed, Medline, and
      the Netherlands Institute for Scientific Information Services. The arguments
      found can help in making a well-considered and careful decision. RESULTS:
      Terminal sedation can be defined as deliberately inducing and maintaining deep
      sleep in terminally-ill patients with recalcitrant symptoms, by using high doses
      of sedatives but without the intention of hastening death. Arguments in favour of
      this approach included: good care provision, useful medical procedure, autonomy
      of the patient, the doctrine of the double effect and an alternative for
      euthanasia and assisted suicide. Arguments against included: impossible to
      communicate due to sedation, responsibility for unintended consequences,
      shortening the length of life, religious and cultural objections, incompetence,
      abuse by the care-provider or the patient and the interest of the physician.
      CONCLUSION: In the literature no overriding moral objections to the use of
      terminal sedation were found. This palliative option may be regarded as a useful
      addition to the existing range of interventions. Although it can never be
      excluded, abuse is not a decisive factor. There seems to be a need for a
      guideline with meticulous criteria and procedures that promotes the responsible
      use of this intervention.

PMID- 14708216
TI  - [Replacement of the femoral head due to fracture of the hip: prognostic factors
      for the duration of hospitalisation, institutionalisation and mortality].
AB  - OBJECTIVE: To identify preoperative factors affecting length of hospital stay,
      residential status and mortality after replacement of the femoral head for a hip
      fracture. DESIGN: Prospective. METHOD: Of the 146 consecutive patients who had
      hemiarthroplasty for a displaced femoral neck fracture in the period 1996-1998,
      data were recorded on age, sex, the residential situation, ambulation, ADL
      dependency, the presence of dementia and the classification according to the
      American Society of Anesthesiologists (ASA). The operations were carried out in
      the IJsselland Hospital, Capelle aan den IJssel, the Netherlands. The study was
      terminated in October 2001. With the aid of uni- and multivariate analysis, the
      relationship was determined between the pre-operative factors and the length of
      hospital stay, need for institutional care, and mortality within 3 years after
      the operation. RESULTS: The study population consisted of 146 patients: 33 men
      and 113 women with an average age of 82 years (range: 60-98). The length of
      hospital stay averaged 21 days (range: 2-98). Independent pre-operative
      predictors for a longer period of hospitalisation were ADL dependency (OR: 1.3;
      95% CI: 1.1-15.2), residence at home (0.7; 0.6-0.8), and poor ambulation (1.1;
      1.0-1.3). The predictors for permanent institutionalisation were: prior stay in
      an institution (4-7; 1.1-19.5) and the presence of dementia (3.9; 1.0-1.5).
      Compared to the general Dutch population of the same age and sex, there was a
      significant excess mortality during the 3 years after the operation and
      especially during the first 12 months. Unfavourable prognostic factors for
      mortality within 3 years after the operation were: poor ambulation before the
      fracture (3.1; 1.8-5.3), an ASA classification of 3 or 4 (2.0; 1.2-3.1) and an
      age over 80 years (2.0; 1.2-3.3). CONCLUSION: The risk factors for a longer stay
      in hospital, placement in an institution or decreased survival in patients who
      underwent hemiarthroplasty as part of the treatment of a hip fracture can already
      be identified at the time of admission. The patients with these risk factors
      should be given special attention during the period of hospitalisation and after
      care.

PMID- 14708218
TI  - [On-demand treatment with gastric acid inhibitors for gastroesophageal reflux
      disease].

PMID- 14708217
TI  - [Primary venous mesenterial thrombosis in three patients].
AB  - Three patients, a woman aged 72, a man aged 25 and a woman aged 42 years,
      presented at the casualty department with a subacute form of primary venous
      mesenterial thrombosis. As symptoms and laboratory findings are aspecific, CT
      scan is the gold standard for the diagnosis of this condition. In these patients
      no cause or predisposing factor was detected, so the disease was considered to be
      primary. Treatment generally consists of anticoagulant therapy and if peritonitis
      is present operation is indicated. Hyperdynamic circulation and inotropica are
      indicated after surgery and in cases of critical illness. Based on clinical
      findings the third patient was treated successfully with anticoagulants only. The
      other two also underwent partial small intestinal resection. All three patients
      were discharged in good health and were prescribed lifelong anticoagulants. If a
      cause of venous mesenterial thrombosis can be found, this must first be treated
      before deciding on whether lifelong treatment with anticoagulants is indicated.

PMID- 14708219
TI  - [Summary of the Dutch College of General Practitioners' practice guideline
      'Anemia'].

PMID- 14708220
TI  - [Diagnostic image (156). A man with a hematoma behind the ear].

PMID- 14708221
TI  - [Guideline 'Treating asthma in children' for pediatric pulmonologists (2nd
      revised edition). II. Medical treatment].

PMID- 14708222
TI  - [Cytomegalovirus infection in pregnant women. Diagnosis and interpretation of
      examination results].
AB  - Changes of the immune status are decisive in the pathogenesis of cytomegalovirus
      infection, which is a cause for the intrauterine infection. Therefore, complex
      immunological and virological examinations are advisable to make in pregnant
      women with compromised obstetrics history, pathological pregnancy course and with
      indirect signs of intrauterine fetus infection for the sake of choosing an
      optimal tactics of observation and treatment.

PMID- 14708223
TI  - [Key role of Asp16 in proteolysis of influenza A NP protein by caspases in
      infected cells].
AB  - The main nucleocapsid protein NP (molecular weight--56 kD) of human influenza A
      virus (IAV) was found to be subject to the N-terminal proteolysis in position
      Asp16 with production of aNP (molecular weight--53 kD) in the infected cells'
      apoptosis. It was assumed that NP of avian and animal influenza viruses was not
      subject to proteolysis since it has Gly16. To verify the above assumption the NP
      chimeric gene of human influenza virus was developed; Asp16 was replaced by Gly
      by means of "site-oriented" mutagenesis in the above gene, after that, the
      A/WSN/33 (H1N1) mutant of human influenza virus with "avian" NP and with point
      mutation (Gly16) was developed by using the method of "reverse genetics". The
      "human" influenza virus with "avian" chimeric NP/Gly16 turned out to be viable
      but had a lower replication velocity versus its wild-nature counterpart. It is
      noteworthy, that the mutant virus caused the cellular apoptosis in the remote
      infection period the way the wild virus did; however, NP of the former was found
      to be resistant to cellular caspasas and was not subject to proteolysis in
      infected cells. The conclusion is that Asp16 in NP molecule of human IAV is
      involved into the regulation process of virus replication and is the key element
      in NP proteolysis by cellular caspasas in cells' apoptosis.

PMID- 14708225
TI  - [Use of atomic force microscopy for detecting intestinal viruses].
AB  - A possibility was demonstrated to use the atomic force microscopy in visualizing
      and identifying a variety of viruses contained in water samples by their
      morphological characteristics (shape and size), which was made by the example of
      3 model objects, i.e. poliovirus, rotavirus and adenovirus. High-quality AFM
      images were made and typical sizes (half-height diameter and mean height) were
      measured for the above objects absorbed in unspecific substrates. Special
      software was elaborated that automated the object identification procedure and
      sped up the analysis process.

PMID- 14708224
TI  - [Comparative analysis of associated live viral vaccines against measles and
      mumps].
AB  - Vaccinations and revaccinations by a new Russian live associated mumps-measles
      vaccine and by a live trivaccine (measies-mumps-rubella)--"Priorix--were
      performed. We followed up 139 infants vaccinated at an age of 12-18 months, 122
      children vaccinated at an age of 6-7 years and 129 persons vaccinated at an age
      of 18-10 years. The combined vaccines were found to be low reactogenic and high
      immunogenic preparations.

PMID- 14708226
TI  - [Effect of home-made narcotics on infectious activity of HIV-1].
AB  - The stability of human immunodeficiency virus, type 1 (HIV-1), strain IIIB, was
      studied in liquid preparations of homemade drugs. The "Vint" preparation
      (containing Methamphetamine and obtained from Ephedrine) as well as "Khanka" (a
      liquid surrogate opiate made from poppy straw) were analyzed within the case
      study. HIV-1/IIIB was shown to maintain its infectious activity in "Khanka" at
      room temperature for least 7 days. The HIV-1 activity in neutralized "Vint" did
      not essentially change after a 30-minute incubation at pH 7.0. While an
      incubation in the acid "Vint" solution entailed a more rapidly decreasing
      activity. However, the virus infection ability preserved during the entire time
      period, during which the drug was fit for injections, i.e. for 30 minutes at room
      temperature or for 20 hours at 4 degrees C. Therefore, the infection virus could
      well preserve in the "Khanka" and "Vint" solutions after its entry, with infected
      blood, of large volumes of the discussed drugs. The mentioned big volumes of HIV
      1 contaminated drugs, shared later into ready-to-use portions, could be the cause
      for HIV-1 dissemination among those who practice the parenteral administration of
      these substances. Besides, "Khanka" was shown to have little or no effect on the
      virus replication to cell culture MT-4. Its presence brought about an
      insignificant 1.5-fold increase in the viral stock (observed on days 2 and 3
      after contamination) only when 2 x 10(5) MT-4 cells per ml and HIV-1/IIIB TCID 50
      0.005 were used.

PMID- 14708227
TI  - [Clinico-immunologic monitoring of HIV-infected patients: comparative analysis of
      indicators, characterizing development of the disease].
AB  - The paper contains the results of a 15-year monitoring (since 1986 to 2001) of
      HIV-infected patients followed up at the clinic of the Institute of Immunology,
      Federal Department "Medbioextrem", Russia's Health Ministry. An analysis of a
      category of HIV-infected persons, who practiced the intravenous consumption of
      drugs since 1997 to 2001, revealed not only concomitant multi-virus infections
      (hepatitis C--68%, hepatitis B--48%, herpes 41%, fungal infections--66% and
      bacterial infections--46%) but also lesions (up to 70%) in the gastrointestinal
      tract and in the hepatic-cellular and hepatic-biliary systems. It was established
      that, when only immunological indices are taken account of in presence of multi
      virus infections, it does not ensure an adequate evaluation of an HIV-patient
      condition. The below biochemical parameters must be necessarily taken into
      consideration: activity of alanine aminotransferase, aspartate aminotransferase
      and of alkaline phosphatase. The changes in the biochemical parameters were shown
      to be essentially higher in HIV patients with hepatitis C virus (HCV) even during
      the 2 initial follow-up years, when the immunological parameters are in the norm
      or even insignificantly below it. A comparative analysis of dynamic clinical,
      immunological and biochemical indices was made within the case study for the
      purpose of defining the prognostic criteria for HIV progression scenarios.

PMID- 14708228
TI  - [Possibilities of culturing mutant variants of Ade12 adenoviruses in 293 cell
      culture].
AB  - The results of polymerase chain reaction and of DNA sequencing of the Adel2
      mutant variant of adenovirus serotype 5, passaged 10 times and capable of
      selectively infecting and lysing the p53-deficient human tumor cells, are
      indicative of a high stability of its genotype and of the phenotypic properties
      acquired by it in successive passage on 293 cells. The absence of admixtures of
      wild-type adenovirus was clearly shown in the cultivation and passage processes.
      It was revealed in an experimental analysis of virus-productive properties of the
      studied continuous cell culture 293 by using the method of multilayer
      cultivation, that the maximal Adel2 yield is obtained at the 50% cytopathic
      effect. Virus doses, that are effective for cell-culture contamination, are
      within a range of 100-10 TCPE50 per cell. In order to spare the viral material,
      the infecting dose of 10 TCPE50 per cell was chosen to infect a cell monolayer.

PMID- 14708229
TI  - [Features of interferon and cytokine production in genital herpes].
AB  - The impaired production of INFs and of other cytokines at different stages of
      their synthesis in patients with genital herpes before and after treatment were
      shown to reflect the specificity of the immune response in the mentioned
      pathology. An activation of the cellular and humoral immunity according to the
      Th1 and Th2 types was observed in patients with genital herpes. The stimulated
      activity of Th1, B-lymphocytes and of natural killers (NK) as well as suppression
      of Th2 occurred in the initial treatment stage by acyclovir (10 days), which
      brought about a positive clinical effect in a majority of cases. A correlation
      between the IFN status and cytokine profile, on the one hand, and an effect of
      therapy in genital herpes, on the other hand, was demonstrated. Finally, the
      monitoring of the IFN and cytokine status in each patient is needed for choosing
      a treatment scheme and for prognosticating a therapy efficiency.

PMID- 14708231
TI  - [Detection of picobirnaviruses by electrophoresis of RNA in polyacrylamide gel].
AB  - Double-segment profiles typical of picobirnavirus (PBV) were detected (during
      1994-2001) in nucleic acids extracted from feces of children (3 cases) and calf
      (1 case) with diarrhea by using the method of electrophoresis. The human genomic
      PBV segments migrated in the polyacrylamide gel (PAAG) as dsRNA segments sized
      1.7 and 2.4 kbp for small and large segments, respectively; the similar calf
      sizes were 1.5 and 2.6 kbp. PBVs were detected in various places of the Nizhny
      Novgorod Region and at different time periods. It was for the first time that the
      PBV circulation was proven to be present in Russia's territory. However, their
      association with diarrhea was not reliably established, and the pathogenic PBV
      potential needs further investigations.

PMID- 14708230
TI  - [Properties of blood serum from reindeer and results of using it in virology and
      biotechnology].
AB  - The blood serum of the reindeer does not virtually contain any antibodies to
      respiratory and intestinal viruses widely spread among the cattle. The reindeer
      blood serum is comparable with the bovine serum by the contents of chlorides,
      hemoglobin, total protein and protein fractions; however, it is different from
      the latter by a 2.5-fold higher content of glucose and by a higher osmotic
      pressure. The serum stimulates the mitotic cell activity and cell monolayer
      production; it also contributes to accumulating the cytopathogenic viruses in
      cell culture. 5- and 10%-serum, when added to a nutrient medium, ensures the
      reproduction of bovine leucosis virus and the accumulation of the antigen of this
      virus in a continuous cell culture that is chronically infected with the virus.
      Finally, the reindeer serum stabilizes the viability of ovocytes and stimulates
      the bovine embryo development at transplantation.

PMID- 14708232
TI  - [Use of guinea pigs for assessing the efficacy of vaccines against Lassa fever].
AB  - The use of guinea pigs as a laboratory model was proven to be appropriate in
      investigating the vaccines developed against Lassa fever at the preclinical study
      stage. An adapted variant of Lassa virus was cultivated, which caused death of
      guinea pigs with respect for an agent's dose. Finally, it was shown to be
      possible to investigate the immunogenic and protective properties of the
      inactivated antigen of Lassa virus in experiments with guinea pigs.

PMID- 14708233
TI  - [International symposium on military-civilian cooperation in surveillance and
      control of influenza].

PMID- 14708234
TI  - [Choice of a method of surgical treatment of urinary bladder neoplasms].
AB  - The results of treatment of 850 patients with urinary bladder cancer (UBC) are
      analysed. Precise staging of the tumor should be made in the following order:
      suprapubic ultrasonic investigation (USI), cystoscopy and microcystoscopy,
      transrectal, transurethral USI. Indications for different treatments are
      outlined: typical and atypical papillary fibroepithelioma, papillary cancer in
      stage T1 should be managed with TUR after previous electrocoagulation; cancer in
      stage T2-3--with urinary bladder resection and uni- or bilateral pelvic
      lymphadenectomy; total papillomatosis, multiple lesions in stage T3, in cases of
      recurrent cancer--with cystectomy including one-stage or multistage replacement
      of the urinary bladder by intestinal transplant. The only physiologically sound
      method of treating patients after cystectomy with ureterocutaneostomy and
      ureterocolostomy is creation of intraperitoneal intestinal urinary bladder with
      reestablishment of transurethral urination. Arguments against creation of
      artificial urinary bladder made of detubularized segments consist in the absence
      of advantages.

PMID- 14708235
TI  - [Is maximal androgenic blockade necessary in the treatment of prostatic cancer?].
AB  - As the literature data give arguments both pro and contra wide use of maximal
      androgenic block (MAB) in the treatment of prostatic cancer, the authors studied
      MAB in 200 patients. They came to the conclusion that MAB can be applied in
      patients with symptoms of disseminated prostatic cancer as neoadjuvant therapy
      before prostatectomy and as neoadjuvant and adjuvant therapy in planning
      radiotherapy.

PMID- 14708238
TI  - [Combination surgery in radical nephrectomy].
AB  - In 18 of 487 patients (11 males, 7 females) operated for renal cancer, radical
      nephrectomy was made simultaneously with cholecystectomy (n = 14) and prosthetic
      repair of the abdominal aorta (n = 4). A transabdominal approach was used in all
      the cases. Duration of radical nephrectomies from the transabdominal approach
      varies from 95 to 180 min while simultaneous operations lasted from 130 to 228
      min. Cholecystectomy increased duration of the operations by 25-55, aortic repair
      -by 60-90 min. Conduction of concomitant operations had no negative effect on the
      course of postoperative period or on the number of complications. 18 cases of
      simultaneous operations (radical nephrectomy and cholecystectomy or aortic
      repair) showed that there was neither increased number of complications nor
      duration of hospital stay. Cholecystectomy can be made from the same incision as
      radical nephrectomy whereas aortic repair demands the middle approach which is
      not convenient for performance of radical nephrectomy.

PMID- 14708236
TI  - [Clinical significance of histological types of prostatic cancer].
AB  - Biopsy material obtained from 310 patients with prostatic cancer (PC) was used in
      the study of the incidence rate of different PC histological types, of tumor cell
      immunophenotype and differentiation by Glison. The results of the study have
      shown that definition of the tumor histological type and tumor immunophenotype
      facilitates identification of tumors with the most malignant potential.
      Therefore, this definition should be included into the diagnostic complex in the
      study of PC. Choice of treatment policy should not be based only on
      differentiation of the tumor process by Glison. The decision should be made only
      after establishment of histogenesis and immunophenotype of tumor cells. The
      presence of neuroendocrine differentiation is an unfavourable prognostic factor.

PMID- 14708237
TI  - [Local recurrence of renal cell carcinoma after nephrectomy].
AB  - Despite significant advances in surgical oncourology, local recurrence of renal
      cell carcinoma (RCC) remains a serious problem both for the doctor and the
      patient. Our study of treatment outcomes in local recurrent RCC consisted in a
      retrospective analysis of 13 patients with a local RCC recurrence in the renal
      fossa treated with surgical resection alone between 1991 and 2003. Twelve
      patients demonstrated no evidence of distant metastases at the time of the
      recurrence. One patient had a synchronous metastasis to the contralateral adrenal
      gland. A mean recurrence-free interval was 14.6 months (range 2-96 months) after
      nephrectomy. 46% patients demonstrated symptoms of weight loss, fatigue and
      lumbar pains. The source of local recurrence in 2 patients was metachronous
      metastases to the ipsylateral adrenal gland, in 1 patients--a tumor thrombus in
      the remnant of the left renal vein, in 3--soft tissues of the renal fossa and in
      7--metastases to the regional lymph nodes. 13 resections were performed with one
      intraoperative death and one immediate postoperative death. Splenectomy was made
      in 2 patients, resection of the stomach in 1, distal pancreatectomy in 1,
      resection of the inferior vena cava in 3, aorta in 1. The average blood loss was
      800 ml (300-4500 ml). Up to now 6 patients survived. Of 5 decreased patients 4
      died of progressive disease in 1, 4, 10 and 16 months. 1 patient died of cause
      unrelated to cancer recurrence in 14 months. Out of 6 alive patients 4 have no
      signs of the disease for, on the average, 31.6 months (range 4-78 months) and 2
      patients have obvious progression of the disease (1--repeated local recurrence, 1
      -distant metastases) 9 and 15 months after the operation. We believe that an
      aggressive surgical approach to a local RCC recurrence can produce an increase in
      disease-free survival and significantly improve quality of life for such
      patients.

PMID- 14708239
TI  - [Acute pyelonephritis in diabetes mellitus].
AB  - The authors present treatment policy in acute pyelonephritis (AP) associated with
      diabetus mellitus (DM) and analyse treatment efficacy basing on the material on
      214 patients. A clinical course of AP in the presence of DM has some specific
      features. The disease manifests primarily with clinico-laboratory signs of DM
      decompensation. Lack of insulin therapy effect in DM decompensated patients
      indirectly points to acute, especially purulent, pyelonephritis. High
      temperature, abnormal leukocytic blood picture, leukocyturia, hypercreatininemia
      in patients with insulin-resistent DM demands urological examination. Renal and
      urinary pathology is prompted by x-ray picture of atonic dilation of the
      caliculopelvic system and ureter in neuropathy. Vesicoureteral reflux, tower-like
      deformation of the urinary bladder, ureterohydronephrosis in DM patients are
      readily diagnosed with cystography, excretory urography and ultrasonic
      investigation. Therapeutic policy must be based on pyelonephritis form, severity
      of DM and efficacy of conservative therapy. No response to therapy, increasing
      academia and intoxication show failure of conservative treatment and absolute
      necessity of surgery. In extended purulent acute pyelonephritis preference is
      given to primary nephrectomy. The differentiated policy of acute pyelonephritis
      treatment led to DM remission and therapeutic response in 84.6% patients. Total
      lethality was 15.4%. Its cause was a severe condition of the patients.

PMID- 14708240
TI  - [Role of cytokines in the diagnosis of chronic prostatitis].
AB  - Chronic prostatitis affects 30-60% males and significantly deteriorates quality
      of their life. Clinical and experimental investigations have revealed changes in
      immune status in the onset and development of prostatic inflammation. As some
      other urologists, we made an attempt to determine the role of cellular immunity
      and immunoglobulins in the diagnosis of chronic prostatitis. The study was made
      in 30 patients with chronic abacterial prostatitis (mean age 42.5 years, duration
      of the disease 1.8 years). In addition to standard examination, all the patients
      have undergone analysis of the immune status and measurement of proinflammatory
      cytokines (TNF alpha and IL-12b) in biological media: blood serum, urine,
      ejaculate, prostatic secretion. The patients had moderate symptoms: IPSS--10.4
      scores, life quality index--4.3 scores, on the average. Prostamol-uno was given
      to all the patients in a standard dose 1 capsule (320 mg) a day for 3 to 6
      months. The results were processed statistically. A good effect of prostamoluno
      was registered in 26 patients, a satisfactory one--in 2. Two patients refused to
      take prostamol-uno because of lack of a prominent effect. The scores of IPSS
      lowered from 10.4 to 6.3 (by 39%), life quality improved by 42%. Ultrasound
      monitoring of the size of the prostate showed no significant changes in the size.
      Tolerance was good in all 30 patients. Side effects were absent. After 3 months
      of the treatment serum, urine, ejaculate and prostatic secretion cytokines
      changed. TNF alpha elevated while IL-1 beta level lowered almost to normal value.
      In 6 months both IL-1 beta and TNF alpha returned to normal values confirming
      stabilization of cytokine system and the end of inflammation. Cellular immunity
      did not change much. Thus, as inflammation in prostatic tissue is characterized
      by elevation of proinflammatory cytokines, in diagnosis of chronic prostatitis it
      will be valid to use markers TNF alpha and IL-1 beta as criteria of immune
      prognosis of prostatic exacerbation. Prostamol-uno does not induce changes in
      lymphocyte populations and impairment of immune status.

PMID- 14708241
TI  - [Application of the preparation "vitamax" in the complex treatment of chronic
      prostatitis complicated by sexual dysfunction].
AB  - A multivitamin complex Vitamax was given to 65 patients with chronic prostatitis
      who retained sexual disorders after basic treatment. Mean age of the men was 41
      +/- 10 years (25-67 years). The efficacy of the drug was assessed by the data
      obtained with Male Copulative Function questionnaire. All the patients were found
      to have mixed sexual dysfunction. Vitamax was taken in a dose 2 capsules a day
      before a morning meal, a total of 30 capsules a course. After the treatment all
      the patients improved their copulative function. Thus, Vitamax is an effective
      drug in sexual dysfunctions related to chronic prostatitis, the efficacy being
      higher in young men. Side effects were absent.

PMID- 14708242
TI  - [Gentos in the treatment of chronic abacterial prostatitis].
AB  - Gentos was given to 46 patients with chronic abacterial prostatitis. The results
      of the treatment were analysed for 39 of them. Compared to control group,
      efficacy of gentos was 64.5-71.8% versus 53.6%. It can be used both as
      monotherapy and in combination with other modalities. Side effects of gentos were
      not registered.

PMID- 14708243
TI  - [Our experience in the use of prostatilen in urology].
AB  - Prostatilen was used in 1115 patients with chronic pyelonephritis and
      prostatitis. It is shown that prostatilen has a corrective effect on
      hemocoagulation and immunity disorders, restores microcirculation, suppresses
      inflammation in the kidney and prostate. Thus, prostatilen is a pathogenetically
      sound drug for treatment in urogenital inflammation while in chronic prostatitis
      it can be used as a basic therapy.

PMID- 14708244
TI  - [Surgical treatment of long ureteral strictures].
AB  - The paper reviews experience, specific features and outcomes of surgical
      treatment of 115 patients (60 males, 55 females) with long strictures and defects
      of the ureter. Renal and ureteral malformations, acquired strictures were
      detected in 14 (12.2%) and 101 (87.8%), respectively. The following
      reconstructive operations were made in 102 patients: ureterocalicoanastomosis by
      Neuvert (n = 3), specially designed original plastic repair of the lumbar ureter
      (n = 3), ureterolysis (n = 7), indirect ureterocystoanastomosis (n = 39),
      appendicoureteroplasty (n = 2), intestinal plastic reconstruction of the ureters
      and urinary bladder (n = 43), autotransplantation of the kidney (n = 3).
      Postoperative complications developed in 13 (11.3%) patients. No lethal outcomes
      occurred. Urinary tracts improved hemodynamics in all the patients. Recovery of
      ureteral passage in its long strictures necessitates atypical surgery. These were
      listed above. The proposed method of lumbar ureter replacement by mobilization
      and raising urinary bladder wall together with relevant ostium and pelvic ureter
      is perspective.

PMID- 14708245
TI  - [Choice of surgical method in the treatment of varicocele].
AB  - The data are presented on 788 patients with varicocele and impairment of
      spermatogenesis. All the patients were divided into two groups. Group 1 consisted
      of 240 patients not examined with ultrasound dopplerography who had undergone
      Ivanissevich operation with estimation of spermatogenesis before and 12 months
      after the operation. Improvement on the spermatograms was observed in 167 of 227
      (73%) patients. Group 2 consisted of 548 patients. Hemodynamic alterations were
      examined in 342 (62.4%). After this examination they were operated by
      Ivanissevich. Improvement of spertmatogenesis was achieved in 285 (90.4%)
      patients. Sapheno-testicular intervenous anastomoses were established in 183
      patients. 168 (92%) of them improved spermatogenesis. Recurrences were detected
      in 19 (8%) and 10 (5.4%) patients of groups 1 and 2, respectively. The above
      treatment policy promoted recovery of sperm fertility in operated patients and
      makes recurrences less frequent.

PMID- 14708246
TI  - [Variants of hermaphroditism (clinical findings)].
AB  - False and true hermaphroditism (FH and TH) are often encountered in surgery for
      hypospadia. A clinically validated classification of various types and variants
      of hermaphroditism is proposed. FH is divided into male FH and female FH. TH also
      falls into two categories: TH without anomalies of external genitalia and that
      with these anomalies. The latter category has three variants: 1) all genitalia of
      males or females and some genitalia of the other sex; 2) some female and male
      organs in various combinations; 3) all organs of both sexes. All TH variants are
      illustrated by 5 case reports. These patients were thoroughly examined and their
      sex was surgically corrected.

PMID- 14708247
TI  - [Experience in the clinical application of semirigid mini-urethral endoscopes in
      the diagnosis and treatment of urinary bladder diseases].
AB  - We compared efficacy and safety of clinical application of modern semirigid
      miniureterorenoscopes (MURS) and standard hard-lens ureterorenoscopes (URS). The
      results of 335 transurethral endoscopic operations on the ureter have been
      analysed. Positive results of ureteroliths elimination by lithotripsy and
      lithoextraction were observed in 100 (77.5%) patients of group 1 (hard-lens URS)
      and in 175 (94.6%) patients of group 2 (semirigid MURS). Ureteral perforation
      occurred 3 times more often in group 1 patients than in group 2 (3.1 and 1.08%,
      respectively). A total number of complications observed in group 1 and 2 in the
      course of transurethral ureterolithotropsy and lithoextraction reached 6.3 and
      1.08%, respectively. Ureterolithotomy was performed in group 2 eight times less
      frequently than in group 1 patients (2.1 and 17.9%, respectively).
      Ureteropyeloscopy made by semirigid MURS is a valuable therapeutic and diagnostic
      aid which raises efficacy of transurethral endoscopic manipulations,
      significantly lowers traumaticity of the upper urinary tracts and reduces to
      minimum the number of intra- and postoperative complications.

PMID- 14708248
TI  - [X-ray and endoscopic diagnosis and treatment of ureteropelvic structure segment
      and of the ureter].

PMID- 14708250
TI  - [Efficacy and safety of the application of cialis for erectile dysfunction].

PMID- 14708249
TI  - [Long-term surgical treatment outcome in ureteral neuromuscular dysplasia in
      children].
AB  - 178 patients with ureteral neuromuscular dysplasia (UND) treated surgically were
      followed up for maximum 8 years. The following operations were made: resection of
      the stenosed part with antireflux operation by Politano-Leatbetter, Hendren
      operation, Lopatkin-Kalichinsky operation. Functional results depended on the
      condition of leiomyocyte regenerative reserves, deficiency of secretory renal
      function and the surgical method. In ureteral achalasia (by N. A. Lopatkin's
      classification) it is recommended to perform resection of the stenosed part by
      Politano-Leatbetter antireflux technique, in megaureter and ureterohydronephrosis
      Lopatkin-Kalichinsky operation is preferable.

PMID- 14708251
TI  - [Diabetic cystopathy].

PMID- 14708252
TI  - [Hypertension and pregnancy].
AB  - 5-10% of all pregnancies are complicated by high blood pressure; in 70% of cases
      there are no signs until 20 weeks of gestation; 30% are seen in women with
      preexisting hypertension. Pre-eclampsia (proteinuric hypertension) is one of the
      most severe diseases in pregnancy. Maternal mortality and morbidity are high. The
      outcome of pregnancies with preexisting (mainly essential) hypertension is much
      worse than that of acute hypertension and depends on duration and severity of the
      disease. Often chronic hypertension develops from acute hypertension in
      pregnancy. This article describes the various types of hypertension in pregnancy,
      diagnosis, complications and management strategies.

PMID- 14708253
TI  - [Therapy of hypertension in kidney diseases].
AB  - The number of patients requiring chronic renal replacement therapy due to
      hypertension and diabetic nephropathy has increased steadily over the past decade
      in Switzerland. The level of blood pressure represents one of the major risk
      factors for the progression of renal diseases. Thus, treatment of hypertension is
      the cornerstone in the primary and secondary prevention of diabetic nephropathy
      and in particular in decreasing the rate of progression of chronic renal
      diseases. The WHO guidelines for the treatment of hypertension recommend a target
      blood pressure of < 130/80 mmHg for patients with renal failure and/or diabetes
      mellitus. Blood pressure should be lowered to < 125/75 mmHg in patients with
      proteinuria > 1 g/d and renal failure regardless of the etiology of the renal
      disease. Based on several intervention studies it is well established that
      antagonists of the renin-angiotensin system should be part of the
      antihypertensive regime in those patients. Besides their antihypertensive action,
      it has become evident that the renoprotective effect of these agents is also
      mediated by factors independent from changes in blood pressure. However, in most
      patients with chronic renal failure it is often necessary to use multiple drugs
      to lower blood pressure to target values. Often a combination of an ACE-inhibitor
      with a calcium-channel blocker is used for this purpose. The goal of the
      antihypertensive therapy in these patients is not only to lower blood pressure to
      reduce cardiovascular risk, but also to reduce proteinuria and to reduce the rate
      of loss in renal function or even prevent further progression.

PMID- 14708254
TI  - [Modern therapy of hypertension].
AB  - Patients with essential arterial hypertension either have or do not have
      compelling reasons for specific drug classes. Patients lacking a compelling
      reason for a specific drug class are those without target organ damage (e.g. left
      ventricular hypertrophy, microalbuminuria, proteinuria, atherosclerosis) and
      without comorbidities. In these patients antihypertensive treatment can be
      initiated with Diuretics and perhaps Betablockers. Calciumantagonists, ACE
      Inhibitors and Angiotensin II-Receptorenblockers (Sartans) are unlikely to be
      superior. However, adverse effects, patient preferences and antihypertensive
      efficacy of a drug in the particular individual ultimately determine the "choice"
      of the medication. In patients with a compelling reason for an individual drug
      class, i.e., in patients with target organ damage (e.g. left ventricular
      hypertrophy, microalbuminuria, proteinuria) or very high cardiovascular risk
      (e.g. Diabetes) Angiotensin II-Receptorblockers or ACE-Inhibitors should be used
      initially. In many hypertensives blood pressure will normalize in response to a
      combination therapy only. Usually, addition of a low dose thiazide to another
      drug class is the most beneficial combination. In most patients resistant to
      therapy, a 24-h-ambulatory blood pressure measurement to exclude white coat
      hypertension or a white coat component, evaluation of medication compliance, non
      pharmacological measures and the tailored use of diuretics and other
      optimizations of therapy will lead to success.

PMID- 14708255
TI  - [Periprosthetic osteolysis].

PMID- 14708256
TI  - [Comment on article concerning preoperative risk assessment in general practice].

PMID- 14708257
TI  - Legal anxieties and end-of-life care in nursing homes.
AB  - Many persons spend their final days as nursing home residents. It has been
      suggested that one set of factors powerfully and unfavorably influencing the
      quality of end-of-life (EOL) care provided in American nursing homes involves the
      anxieties that nursing home providers experience regarding potential negative
      legal entanglements and repercussions associated with the provision of EOL care
      to their residents. This article critically examines the hypothesis that the
      quality of EOL medical care provided in nursing homes often is skewed in a
      perverse way because providers are driven unduly by legal apprehensions. The
      author offers practice and policy recommendations for trying to resolve or
      mitigate the tension present between legally defensive practice (real or
      perceived) by nursing homes, on one hand, and ethically optimal EOL care, on the
      other.

PMID- 14708258
TI  - Schiavo v. Schiavo. Amicus curiae memorandum of Governor Bush.

PMID- 14708260
TI  - In re guardianship of Theresa Marie Schiavo: opinion of the Court of Appeal of
      Florida.

PMID- 14708259
TI  - In re guardianship of Theresa Marie Schiavo: brief of Amici curiae not dead yet
      et al.

PMID- 14708261
TI  - Women have a right to know: testimony before the Massachusetts Joint Health Care
      Committee.

PMID- 14708262
TI  - Miller v. HCA, Inc.

PMID- 14708263
TI  - Grubbs v. Barbourville Family Health Center.

PMID- 14708264
TI  - 66 Federal Credit Union v. Tucker.

PMID- 14708266
TI  - Stray thoughts on SARS.

PMID- 14708265
TI  - Malaria 2003: the malaria parasite is still evolving, but so are the options for
      prophylaxis.

PMID- 14708267
TI  - The role of the regional microbiologist.

PMID- 14708268
TI  - Guidelines for malaria prevention in travellers from the United Kingdom for 2003.
AB  - This updated guidance from the Advisory Committee on Malaria Prevention for UK
      Travellers provides the essential information for healthcare workers who advise
      travellers. The many personal, visit and location-specific factors that need to
      be taken into account are discussed. Tables include the available antimalarials
      for prophylaxis and for standby treatment, appropriate choices of regimen by
      region and country for malarious areas, and the adjustments needed for children
      and in concomitant disease. There is greater emphasis on mefloquine, doxycycline
      and atovaquone/proguanil as the three options for highly chloroquine-resistant
      falciparum malarious areas, and changes in emergency standby medication.

PMID- 14708269
TI  - Malaria prophylaxis for long-term travellers.
AB  - These guidelines are designed to assist healthcare workers who are advising long
      term travellers on malaria prophylaxis, defined for the purpose of this document
      as those travelling for longer than 6 months. The document focuses on long-term
      use of antimalarials for adults, but also identifies specific issues for women
      and children. However, data on the long-term use of antimalarials is limited for
      all travellers and few data are available on the incidence of malaria in
      travellers overseas or, indeed, deaths overseas from malaria. Whilst all
      available evidence is taken into account, the advice provided also reflects
      experienced professional opinion. This document has been written on behalf of the
      Health Protection Agency's Advisory Committee on Malaria Prevention for UK
      Travellers, and is designed to act as a supplement to the 'Guidelines for malaria
      prevention in travellers from the United Kingdom for 2003'. The latter document
      contains a more complete description of antimalarials and additional preventive
      measures, together with recommendations for malaria chemoprophylaxis for
      individuals countries. Decisions on the terms under which different drugs are
      licensed for use are the responsibility of the Committee on Safety of Medicines.
      This paper should also, therefore, be used in conjunction with Summary of Product
      Characteristics (data sheets).

PMID- 14708270
TI  - SARS: UK public health response--past, present and future.
AB  - The emergence of severe acute respiratory syndrome (SARS) in China, the
      occurrence of epidemics of SARS in China and a number of Southeast Asian
      countries, and its spread to countries elsewhere, have presented major challenges
      to public health systems throughout the world. Although very few true cases of
      SARS were detected in the United Kingdom, the public health response to the
      threat of SARS was considerable. The main components of this response were the
      early detection, isolation and reporting of cases, and the provision of
      comprehensive information to health professionals, cases, their contacts and the
      public. The development of the response to SARS raised a number of more general
      issues relevant to future infectious epidemic threats. Although the World Health
      Organisation has now declared SARS 'contained', the possibility of re-emergence
      is ever present. All countries will need to be vigilant and plan their response
      to the possibility of a renewed SARS epidemic.

PMID- 14708271
TI  - Screening international travellers in China for SARS.
AB  - Faced with the spread of SARS through international travel, the World Health
      Organisation (WHO) advised against inessential travel to certain areas with local
      SARS transmission, and also the screening of travellers from such areas. This
      report looks at the steps taken in China for the screening of travellers.
      Travellers were asked about contact with SARS and possible symptoms, were
      screened for high fever, provided with health information and observed for any
      clinical signs. Arrangements were in place for dealing with ill travellers and
      for contact tracing of fellow travellers. There were also extra measures that
      could only be justified by the reassurance they provided. The overall impact of
      these measures in preventing international spread of SARS is unknown, but the
      experience could contribute to the control of future epidemics.

PMID- 14708272
TI  - Diagnosis of invasive pneumococcal infection by PCR amplification of
      Streptococcus pneumoniae genomic fragments in blood: a multi-centre comparative
      study.
AB  - The increasing interest in the prevention of pneumococcal disease by immunisation
      necessitates improved organism-specific surveillance. This is particularly the
      case with regard to the contribution of Streptococcus pneumoniae infection to
      community-acquired pneumonia where blood cultures are often negative and sputum
      culture results ambiguous. Examination by PCR of blood samples taken at hospital
      admission offers one possibility for such improvement. The sensitivity,
      specificity and convenience of three pneumolysin gene PCR assays were compared in
      a large study, using EDTA blood from 175 patients (95 with proven pneumococcal
      bacteraemia, 80 with bacteraemia due to other organisms). The assays used were a
      PCR-enzyme immunoassay, a hybridisation probe assay run on the Roche LightCycler
      and a hydrolysis probe (TaqMan) assay run on an ABI 7700. Overall samples from
      only 57% of patients with bacteraemic pneumococcal infection yielded a positive
      result in at least one assay. Individual sensitivities ranged from 45%
      (TaqMan/ABI) through 35% (PCR-EIA) to 21% (Hybridisation/LightCycler).
      Specificity (PCR negative in the 80 control patients) ranged from 97-100%. The
      TaqMan/ABI assay was run in two centres and concordance between results was
      91.4%, discrepancies being associated with very weakly positive samples. Overall,
      the TaqMan/ABI was the most sensitive and convenient assay; however, this method
      does not appear to offer any significant improvement over conventional blood
      cultures and is unlikely to be sufficiently sensitive to confirm a pneumococcal
      aetiology for non-bacteraemic pneumococcal pneumonia. For the present, therefore,
      blood culture is the preferred option.

PMID- 14708273
TI  - Pneumococcal vaccination programme in over 65s and at-risk groups: the Dumfries
      and Galloway experience.
AB  - Implementation of a systematic pneumococcal vaccination campaign in over 65s and
      at-risk groups is described for Dumfries and Galloway, South West Scotland. A
      successful programme is achievable in health boards and health authorities with a
      modes degree of effort. Problems are few, costs are manageable if the campaign is
      combined with the flu vaccination campaign, and acceptability to and uptake by
      the population is high. The lessons learned have implications for all regions of
      the United Kingdom as pneumococcal vaccination programmes are scheduled for
      introduction over the next three years.

PMID- 14708274
TI  - Influenza and adult hospital admissions for respiratory conditions in England
      1989-2001.
AB  - Influenza is recognised as a major cause of excess hospital admissions during
      winter months. This study sets out to quantify admissions related to influenza
      during the last twelve winters and to examine the importance of age. Total
      admission data for respiratory disorders in adults for England during the years
      1989 to 2001 have been used. Weekly admission data were examined in five-year age
      bands. Influenza epidemics were identified from clinical incidence data in the
      community. Baseline admission levels were determined by averaging weekly
      incidence data from weeks in which there was no clinical evidence of influenza
      activity. Excess admissions were estimated from the difference between observed
      and baseline admissions after adjusting the baseline in each group and year for
      the secular trend. Estimates for all adults were consolidated from the five-year
      age bands. Bed occupancy was estimated by applying data on average bed stay to
      excess admissions in age- and year-specific groups. We estimated 2.7% of all
      respiratory admissions were related to influenza. Excess admissions were strongly
      age related. Of the 16,227 annual average excess, 52% occurred in persons over 75
      years. The excess admissions account for an average 145,544 bed days annually,
      two thirds (69%) in persons over 75 years. Annual excess bed occupancy was
      highest in 1999/2000 (39,512) though 30,000 excess admissions per year is not
      unusual. Hospital admissions due to influenza remain a major problem for health
      service delivery particularly in elderly populations. Though robust programmes of
      vaccination are needed, vaccination by itself will not eliminate the impact of
      influenza on hospital admissions in winter.

PMID- 14708275
TI  - Appropriateness of thresholds currently used to describe influenza activity in
      England.
AB  - The timing and magnitude of influenza virus activity in England each winter
      remain unpredictable. Nevertheless, it is important to describe levels of
      activity in a timely manner, using defined 'threshold values'. This informs
      public health practitioners and the general public of the level of influenza
      virus circulation, and provides an indication of when sufficient activity is
      occurring in the community to warrant the use of antiviral drugs. Data presented
      here suggest that the current numerical thresholds, and their corresponding
      descriptions, are no longer appropriate for the levels of activity recently
      observed in England. Based on integrated clinical and virological data, we
      suggest alternative threshold values of 'baseline' activity (0-30/100,000
      population), 'normal seasonal' activity (30-200/100,000) and 'epidemic' activity
      (> 200/100,000).

PMID- 14708276
TI  - Incidence and prevalence of head lice in a district health authority area.
AB  - There are very few recent studies of the incidence and prevalence of head lice in
      the UK. A population-based questionnaire survey was carried out in a district
      health authority area. Two hundred and four of 235 primary schools (87%) agreed
      to participate. A total of 21,556 of 43,889 (49%) questionnaires were returned by
      parents. Overall 438 children had head lice at the time of the survey, giving a
      prevalence of 2.03%; 8,059 had had lice at some time in the last year giving an
      annual incidence of 37.4%.

PMID- 14708277
TI  - Microbiological quality of food in relation to hazard analysis systems and food
      hygiene training in UK catering and retail premises.
AB  - A meta-analysis of eight UK food studies was carried out to determine the
      microbiological quality of food and its relationship with the presence in food
      businesses of hazard analysis systems and food hygiene training. Of the 19,022
      premises visited to collect food samples in these studies between 1997 and 2002,
      two thirds (66%) were catering premises and one third (34%) were retail premises.
      Comparison with PHLS Microbiological Guidelines revealed that significantly more
      ready-to-eat food samples from catering premises (20%; 2,511/12,703) were of
      unsatisfactory or unacceptable microbiological quality compared to samples from
      retail premises (12%; 1,039/8,462) (p < 0.00001). Three quarters (76%) of retail
      premises had hazard analysis systems in place compared with 59% of catering
      premises (p < 0.00001). In 87% of retail premises the manager had received some
      form of food hygiene training compared with 80% of catering premises (p <
      0.00001). From premises where the manager had received no food hygiene training a
      greater proportion of samples were of unsatisfactory and unacceptable
      microbiological quality (20% retail, 27% catering) compared with premises where
      the manager had received food hygiene training (11% retail, 19% catering) (p <
      0.00001). Where the manager of the premises had received food hygiene training,
      documented hazard analysis systems were more likely to be in place (p < 0.00001).
      Higher proportions of samples of unsatisfactory and unacceptable microbiological
      quality (17% retail, 22% catering) were from premises where there was no hazard
      analysis system in place compared to premises that had a documented hazard
      analysis system in place (10% retail, 18% catering) (p < 0.00001). Our meta
      analysis suggests that the lower microbiological quality of ready-to-eat foods
      from catering premises compared with those collected from retail premises may
      reflect differences in management food hygiene training and the presence of a
      hazard analysis system. The importance of adequate training for food handlers and
      their managers as a pre-requisite for effective hazard analysis and critical
      control point (HACCP) based controls is therefore emphasised.

PMID- 14708278
TI  - Re: HNIG prophylaxis management of hepatitis A in a food handler at a London
      secondary school. Commun Dis Public Health 2003; 6(1): 26-9.).

PMID- 14708279
TI  - The day of the phage.

PMID- 14708280
TI  - Clostridium difficile: towards a standard operating procedure.

PMID- 14708281
TI  - Corporate accountability and corporate killing.

PMID- 14708282
TI  - [The present and future of home care service].

PMID- 14708283
TI  - [The present and future of home care for patients with gastrointestinal malignant
      diseases].
AB  - Home care for patients with gastrointestinal malignancies includes nutritional
      support, chemotherapy and hospice care. Every step should be started alter
      acquiring sufficient information on the disease. Home infusion therapy (HIT) is
      most important for nutritional care because the patient usually cannot eat or
      eats very little. It should be started fast within another symptoms controllable.
      With some problems in access procedure, total calories, formula, catheter
      infection, it is important to treat individually not to over dose. As for home
      chemotherapy, new molecular target-based therapies that prolong tumor dormancy
      are expected to be developed. Regarding home hospice, the control of pain,
      nausea, general fatigue, and other symptoms is the key to continuous home hospice
      care. The medical linkage between hospital and clinic, clinic and clinic and
      skillful visiting nurses is indispensable and the establishment and quality of
      medical systems, networks play an important role in the home care of patients of
      gastrointestinal malignancies.

PMID- 14708284
TI  - [Toward the settlement and development of home care].
AB  - Ever since Sendai Ohshin Clinic inaugurated the operations in 1996, the clinic
      has been involved in the home care of 850 people in total. At present, the clinic
      provides care to 200 people at their homes including 38 people with serious
      diseases under artificial respiration and 40 people with terminal cancer. 513
      people who were under care by the clinic died at home, and it is now quite
      natural that people live at home to the last breath. I noticed various issued
      through the provision of home care in Sendai and want to present the desirable
      direction of medical care using a couple of key words.

PMID- 14708285
TI  - [Practice and problem in hospice and home palliative care].
AB  - In Yamaguchi Red Cross Hospital, hospice services are provided under coordination
      of palliative care for outpatients and for inpatients and home palliative care.
      The Home Nursing Center plays the central roles in home palliative care and needs
      to exclusively provide home medical services. We served for 25% of the patients
      who died of terminal cancer in the palliative care unit or at home in Yamaguchi
      City. In the future hospice and palliative home care services, the system to
      allow patients to choose in-hospital care/outpatient care/home palliative care
      should be established. Home palliative care should be disseminated under the
      coordination of local municipalities, medical institutions and welfare service
      organizations so that patients and families can live meaningful lives at their
      home where they long lived as the place they chose to live.

PMID- 14708286
TI  - [Home medical care service and regional medical plan].
AB  - A home medical service should be promoted as an individual medical plan which
      proactively copes with health problems in daily living. It is categorized into 3
      phases: Health for a patient without long-term disabilities, QOL for a patient
      with long-term disabilities and Peaceful Death for a terminal patient.

PMID- 14708287
TI  - [Consideration of home care for patients with advanced cancer as a surgeon].
AB  - There is a tendency to consider that home care is promoted as an alternative to
      reduce the mean duration of hospital stay. Home care must be carried out
      according to the wish of both the patient himself and his family. At present,
      home care has reached a high levels, so that it can be carried out safely. As a
      surgeon, I think that we must make use of the system of home care established to
      allow patients to live at home when they wish to do so, and I want to let them
      stay in the hospital if they prefer so.

PMID- 14708288
TI  - [Management of home care for the advanced cancer patient from the standpoint of
      home hospice].
AB  - We offer home hospice care to patients with bowel obstruction associated with
      advanced gastrointestinal cancer, who hope to leave hospital and be cared at
      home, if they understand their condition and if their families also hope to live
      with the patients, so that the patients can live at home to the last breath. To
      master various palliative techniques and nursing care services are indispensable
      to assure home hospice care. In this case, 1. guidance about HPN, 2. guidance
      about pain control, 3. arrangement of visiting nurse services and 4. application
      for the long-term care insurance and procurement of the bed and other nursing
      goods needed to be completed before the discharge from the hospital, and it is
      important to complete these preparations rapidly in a short period. The 24-hour
      communication system and appropriate care for new symptoms are the key for
      successfully shifting to home hospice care. At the final stage, it is important
      to support families and repeatedly provide guidance for the peaceful death.

PMID- 14708289
TI  - [Management of cancer patients for discharge by a consultation doctor specialized
      in palliative care].
AB  - As a medical advisor specialized in palliative care, I think the following points
      should be considered regarding management of patients after discharge from a
      tertiary hospital: 1. Information that we should get before the interview and
      examination, 2. Assessment of symptoms, 3. Medications for the management of
      pain, 4. Supportive care to cope with psychosocial problems derived from the
      management of physical symptoms, 5. Help to continue with activities of daily
      life and to cope with the cancer at home, and 6. Characterize of the medical
      advisor as a member of an interdisciplinary team.

PMID- 14708290
TI  - [Discharge and introduction to home care for 70-year-old terminally-ill patient
      with metastatic gastrointestinal cancer].
AB  - There are many problems associated with the discharge and management of
      terminally-ill patients with cancer, A 70-year-old patient with gastro-intestinal
      cancer obstructing his intestinal tract, who is receiving total parenteral
      nutrition through a central intravenous catheter is being prepared for his
      discharge from hospital. The effective management of the discharge of this
      patient and introduction to home care, consisting of visits by physicians and
      community nurses is described.

PMID- 14708291
TI  - [Home care of patients with malignant tumor--from in-hospital care to home care
      viewpoint of cancer care].
AB  - If patients with advanced recurrent gastrointestinal cancer want home care,
      endeavors are made to attain early control of the symptoms and the patients are
      transferred to home care under the team approach while understanding and
      supporting the intention of the patients and families.

PMID- 14708292
TI  - [Management of advanced cancer patients after discharge].
AB  - Our hospital carries the burden of providing high-level medical treatment, and at
      present patients who require constant attention tend to transfer to other
      hospitals rather than return directly home after being discharge from ours. We
      think, however, that the proportion of those who go directly to their homes will
      increase in the future. For this reason, one of our missions is to thoroughly
      understand the physical and social circumstances of each patient and coordinate
      with an area's medical community. For our patients to return home, we believe,
      that we are required to 1. gather sufficient information for them, 2. adjust
      treatment modes and gain firm control of their symptoms, 3. educate the patients'
      family members, 4. adjust family relationships, 5. coordinate area's medical
      professionals, and 6. re-adjust emergency medical services. Furthermore, because
      we are at the first step in the route of patients' return to their home, we need
      to grasp the hopes and desires of the patients once they are home. To meet these
      requirements, we need to know the activities in which patients can be involved at
      home, wishes of other members of their families and acquire information on
      available community resources and supporting organizations as well as thorough
      preparation to make such information widely known and ability to coordinate
      social resources and organizations.

PMID- 14708293
TI  - [Palliative care for the patients and their families].
AB  - This article discusses palliative care for the patients and their families and
      the role of nurses for a smooth change from inpatient services to home care. Home
      is where a patient feels most comfortable. To provide the best possible care it
      is important to respect the decision of the patient and his family maximally and
      QOL takes top priority. Through the participation of home care doctors, home
      health nurses, pharmacists, etc., a 24-hour system can be established to improve
      home care. Simultaneously, the up of a patient self-care agency regards it as an
      importance. However, it is very difficulty for the patients and their families
      demonstrate the identity in the complicated medical situation, and thus providing
      support to them is a function of the nurses. It has been required that nurses in
      hospitals and home health nurses function to raise patients' self-care.

PMID- 14708294
TI  - [Significance of treatment and adequate care in dementia--including point of
      medical comments in health care insurance system for elderly people by doctors].
AB  - Dementia treatment is one of the most important in home medical care. Donepezil
      hydrochloride, a dementia treatment drug available in Japan, is a symptomatic
      therapy but alleviates memory, willingness and feeling disorders and
      significantly improves QOL. Family doctors will be required to diagnose Alzheimer
      disease (AD) but it is very difficult for general physician to diagnose AD. This
      is the reason that the authors devised the simple criteria for diagnosing AD.
      Meanwhile, recent data from a multi-center study of donepezil hydrochloride for
      mild cognitive impairment (MCI) conducted in the US suggest that donepezil
      hydrochloride is also as useful for MCI as for AD. This is considered to suggest
      the significance to start treatment for AD at the early stage. Care for demented
      patients is not only the improvement of the apparent dementia. Recent scientific
      study data may be directly connected to treatment. These days, not a few elderly
      patients with dementia attend "Day-care Service" and the data indicate that
      rehabilitations they have under "Day-care Service" are important and useful. It
      is considered that non-pharmacological treatment may also play an important role
      and necessary to accumulate evidences in the future.

PMID- 14708295
TI  - [Personal hygiene care such as toileting, bathing, dressing and grooming in the
      living enviroment].

PMID- 14708296
TI  - [Nutrition management based on urine collection in patients under home care].
AB  - We calculate the salt intake, the protein intake and the % creatinine generation
      rate, the index for the muscle volume/exercise, based on the sodium, urea and
      creatinine level in the urine in patients under home care and retain the data in
      the database. To date, 45 patients under home care have been enrolled. The mean
      age is 70.9 years (+/- 13.8, SD). The underlying disease treated under home care
      include malignant tumor in 23 patients (51.1%), cerebrovascular disorders in 11
      patients (24.4%), neurological/muscular disorders in 6 patients (13.3%) and other
      diseases in 5 patients (11.1%). The analysis of the data obtained from the
      collected urine has revealed that the % creatinine generation rate was
      significantly low in the patients with neurological/muscular disorders and that
      the % creatinine generation rate, the protein intake and the salt intake were
      high in the patients under the central venous nutrition. The analysis has also
      revealed that the % creatinine generation rate and the protein intake were lower
      in the patients who are less independent in daily lives. These findings
      substantiate that the 24-hour urine collection is useful for the assessment of
      nutritional condition in patients under home care.

PMID- 14708297
TI  - [Home care in Sapporo].
AB  - We established a clinic specialized in home care in Sapporo in July 2001. In
      these 2 years we have provided medical home care service to 160 patients, and 97
      are still receiving regular service. At first we accepted any patients living
      within 16 km from the clinic. However, bad traffic conditions in winter made it
      difficult to visit patients living in districts far away from the clinic.
      Therefore, we planned a network of home care physicians in Sapporo. Now 12 home
      care physicians hold monthly meetings. In Sapporo, meetings of home care related
      workers are organized in each ward, as suggested by the Sapporo Medical
      Association. There is a relatively good supply of home care related services and
      resources, including availability of an important number of visiting nurses.
      Patients being taken care of at home who present an acute exacerbation of
      symptoms are relatively easily accepted by acute hospitals. But those who have
      difficulties in continuing home care due to a sudden change in family conditions
      are not easily accepted by nursing hospitals. Recently, the number of group homes
      and lodging houses for elderly persons has markedly increased in Sapporo. It
      might have some problems in medical support in the near future.

PMID- 14708298
TI  - [The practice of community based medicine in Nagoya City--role of home care for
      patients with neurodegenerative diseases].
AB  - Patients with neurodegenerative diseases by definition, experience slowly
      progressive aggravation of their condition; in the terminal stage many patients
      need some special management, tube feeding or suction, and thus home care is
      often difficult. For home care management, communication among all those
      involved, namely, medical staff, patients and their families, home doctor, nurse,
      physical therapist, helper and hospital, is very important. The results of a
      questionnaire we sent to the patients' families, clearly showed that they would
      hope to take home care as long as possible, be able to consult the specialists
      any time and have a reliable care-manager.

PMID- 14708299
TI  - [Home care practice in Ishigaki Island, Okinawa].
AB  - In Yaeyama district in Okinawa, despite the scarcity of health-care resources for
      home visit, most of the patients used to choose home care instead of in-hospital
      care because of their special beliefs and preference different from mainland.
      Since people resided in a large family and formed a tightly knit community,
      patients were able to receive care from their family and community members.
      However, together with increase in chronic care facilities and modernization of
      the island that have brought downsizing of the family unit and loose community,
      the elderly are facing difficulty in receiving home care due to lack of care
      givers. In order to establish the system to support the patients who wish to
      receive domiciliary care and live at home in their own life style, Yaeyama
      Hospital is expected to provide community-based health-care services 24 hours a
      day. It is essential that medical and welfare professions who are in charge of
      home care maintain close relations in good communication and collaboration.

PMID- 14708300
TI  - [Community based medicine in Japan].
AB  - The community has important roles in the community based medicine and home care
      systems along with the differentiation of the functions of medical institutions.
      Patients under home care receive care of their family, the friends, community
      home care services and medical care by healthcare professionals. Patients can
      live in the community under medical care in a different category from in-hospital
      care. Community based medicine is the manifestation of healthcare supporting
      people who live. Healthcare professionals involved in community based medicine
      are required to give medical education and cooperate with community welfare works
      apart from medical care in the community.

PMID- 14708301
TI  - [Questionnaire survey of the actual working conditions of care-managers].
AB  - In order to clarify the present status of care-managers, a questionnaire was sent
      to 1,714 care-managers working in Kanagawa Prefecture in June 2002. The aspects
      Investigated included their background, amount of care-management and degree of
      achievement, conditions of employment, opinion poll and training system. The
      response rate was 45.6% (782 out of 1,714). Concerning the total number of users
      in care at present, 37% of care-managers had less than 30 people, 24% from 31 to
      50 and, surprisingly, 39% had more than 51 people. However, 42% answered that
      less than 30 was an appropriate number of users, 52% said 31 to 50 and only 6%
      answered that more than 51 people was an appropriate number. The conferences of
      users service representative were held only 8%. Concerning the burden of care
      management, 87% of them answered the evaluation of every month and 86% did the
      conferences of users service representative. The cases requiring much time for
      the support, had problems not only the users but also in the household, who
      lacked the understanding and judgment for long-term care insurance. Most care
      managers needed information on the available services and newly open care-service
      institutions. 27% of care-managers satisfied their care-management, 25%
      dissatisfied and the remainder were neither off nor on. The satisfaction to the
      care-management correlated well with the intelligibility of the management
      leader, motivation regarding care-management and the degree of satisfaction with
      their income. It is concluded that the number of users per care-manager is too
      large, and that unfortunately it might further increase in the future. The
      conferences of users service representative were extremely held too low. It is
      also showed that information of the other service office and informal service
      with the exception of long-term care insurance are required.

PMID- 14708302
TI  - [Discussions on home care of solely living people receiving nursing services at
      the station].
AB  - The number of solely living people receiving nursing services at the station has
      continuously increased to 23 people in the period of four years and six months
      from September 1998 to February 2003. We plan to survey the condition of home
      care of solely living people, which is considered to give hints for future
      nursing.

PMID- 14708303
TI  - [The role of nurses in the introduction of home parenteral nutrition (HPN)].
AB  - HPN makes it possible for patients, who otherwise must remain hospitalized, to be
      discharged and contributes to improve their QOL. We report 3 patients for whom
      HPN was introduced and could either stay out or to be discharged. Both strong
      will to be discharged and self-confidence acquired after a test stay out led the
      patients to HPN. It was important to design the contents of instruction, the
      methods, and the periods according to the comprehension, will and abilities of
      the patients. Since the HPN equipment weighs over 2 kg, it was hard for patients
      in a terminal stage and senile patients to carry them. All 3 patients had the
      cooperation of their families and the nurses to design various additional devices
      and thus continue the therapy at home. The nurses should participate in the
      renovation of the transfer equipment in order to improve the QOL of the patients.
      Moreover, it is important to promote the will of patients though active
      information and to suggest a management plan suitable to their lifestyles.

PMID- 14708304
TI  - [A development of the network for functional trainings in daycare services in a
      large district].
AB  - After the Long-Term Care Insurance (LTCI) regulation has been enacted, all the
      daycare agencies/institutions must provide functional trainings to their clients
      as one of the standard services. However, the regulation is limited only to their
      personnel arrangement rather than the service content, which is left to each
      agency/institution. We feel that functional trainings as a daycare service need
      more attention so that we can bridge the content gaps between
      agencies/institutions. To solve this problem, we planned to send training
      professionals to these daycare providers in the surrounding areas. At the same
      time, we have been holding training courses for daycare stuff and each trainer,
      which contributed to fill the knowledge and skill gaps between these trainers'.
      The purpose of this paper is to report our study with some suggestions about the
      ideal functional trainings in the future daycare services.

PMID- 14708305
TI  - [Evidence base research of social support (convoy) for elderly people who live in
      Hanshin urban area].
AB  - The aim of this study was to find the relative factor between social support and
      mental health of elderly people living in the Hanshin urban area. Using a self
      rated questionnaire under informed consent, we tried to clarify the types of
      social support for elderly people and the relationship between social support and
      life development or mental health at the time of the Great Hanshin Earthquake.
      RESULTS: 477 (male: 146, female 331) people responded. Those who had support from
      their family, friends and/or neighbors showed a better mental score, but the
      group receiving 10% or less social support tended to suffer from depression more
      frequently.

PMID- 14708306
TI  - [Preparation of a manual treatment of pressure ulcers which draws attention to
      moisture of the affected part].
AB  - As for pressure ulcers care, prevention is the most important approach. However,
      pressure ulcers, might develop despite enough care, depending on each person's
      physical condition. As for the treatment of pressure ulcers, maintenance of a
      moderately moist environment (60-70%) is quite important. We propose the use of
      ointment to control the moisture of a pressure ulcer environment. One ointment
      base absorbs moisture, while another provides moisture. We have prepared a manual
      that allows the user to select the medicine according to the degree of moisture
      of the affected part. When the moisture cannot be regulated with one ointment, it
      can be adjusted by mixing two or more ointments. In choosing a drug for external
      use, it is important to pay attention not only to the effect of the main
      ingredient but also to the physicochemical properties of the ointment base that
      serves as vehicle for that active component.

PMID- 14708307
TI  - [A newly opened palliative care ward and the nursing of terminal patients with
      gynecological cancer at our Department of Obstetrics and Gynecology in Tokyo
      Women's Medical University Hospital].
AB  - Seventy-nine terminal patients with gynecological cancer treated in the past 5
      years in our hospital or their families were interviewed on where those patients
      died and the reason why they chose to die in the place. Fifty-two patients
      (65.8%) were died at our hospital, 18 patients (22.8%) at other hospitals, 5
      (6.3%) at other hospice and 4 (5.1%) at home. The 52 patients who died at our
      hospital were asked why they chose to die there. 42 of them (80.8%) wanted care
      at our hospital to the death. 10 (20.2%) had no time to think of home care or
      other institutions because of the sudden change of the condition. The 18 patients
      who died at other institutions were also asked about the reason. 9 of them (50%)
      wanted to die in their hometown or close to their home. 5 of them (27.8%) were
      referred to other hospitals due to brain metastasis or the necessity of
      undergoing dialysis. 2 of them (11.1%) were referred to the institutions which
      provide long-term care. 2 of them (11.1%) were brought into a nearby emergent
      care hospital and died after the sudden change of the condition. The palliative
      care ward in our university hospital can provide continued relationship with
      cancer patients. We had time to talk enough with carcinoma patients and their
      family in the ward, which widened choices of their death place, including home
      death.

PMID- 14708308
TI  - [An undesirable process at a sudden change in home palliative care].
AB  - Patients under home palliative care may occasionally meet an undesirable end
      because the family would call an ambulance in the case of a sudden change. It may
      be caused by lack of family education, a short period under home care, or an
      administrative proceeding. So, we must be careful in home palliative care.

PMID- 14708309
TI  - [Construction of a pharmacy network that supports home medical care].
AB  - Home medical care is recently being promoted thanks to the establishment of the
      related medical insurance system and by patient choice. Home medical care
      requires a collaboration of home treatment, home nursing, and drug supply, and
      within this collaborative network, pharmacists also play the role to supply drugs
      (dispensing). Drugs that used for home care include injectable agents for pain
      control or hygiene management. Therefore, pharmacies need to be furnished with
      clean rooms and clean benches to dispense drugs aseptically. However, because of
      the enormous costs of capital investment and the uncertainty of the number of
      patients who will use pharmacies, a very few pharmacies are adequately furnished.
      The survey has revealed that 76 pharmacies are adequately furnished. It is
      presumed that home medical care will continuously promoted in the future so a
      network of pharmacies that can dispense injectable drugs must be set up under the
      home care support system.

PMID- 14708310
TI  - [Connecting between hospital, clinical and pharmacy--present and future].
AB  - SUBJECT: Along with the promotion of "home medical care", an increasing number of
      clinics provide home medical care as part of their services or are dedicated to
      home medical care partly as a result of the reform of the healthcare system. This
      is considered to be the manifestation of the desire of patients to live their own
      lives and the intention of the healthcare professionals to satisfy patient needs.
      We examine what insurance pharmacies should and must do to provide higher-quality
      services to satisfy such patient needs, this time focusing on the community
      coordination for the purpose of providing the services which can give sense of
      security to patients. METHOD: Cases of HPN during the period from July 2002 to
      June 2003 were subdivided into those in which we were involved before and after
      the discharge from the hospital and those in which we were involved only after
      the discharge from the hospital to home medical care and comparatively studied
      from various perspectives. Existing coordination systems are introduced and
      discussed to achieve the desirable coordination systems. PRESENT AND FUTURE: In
      the home guidance service, some patients consult with us on the issues on which
      they hesitate to consult with doctors or nurses. This suggests that we can
      contribute to the mental care for patients and their care givers. In order to
      make the best use of our position, the coordination with hospitals is essential
      for insurance pharmacies. The degree of contribution to the improvement of QOL or
      the mitigation of anxiety over inexperienced issues is considered to differ
      depending on the preparatory period between the cases in which we were involved
      before and after the discharge from the hospital and those in which we were
      involved only after the discharge from the hospital to home medical care. The
      analysis of the differences in the actual cases is considered to be significant
      to seek for the ideal coordination.

PMID- 14708311
TI  - [An efficacy study of a TPN kit with multivitamin addictive in the HPN].
AB  - When home parenteral nutrition (HPN) is instituted, one should aim at reducing
      the risk of infections, simplifying the operation, and improving the patient's
      QOL, while considering the differences between the hospital and home. As for
      simplification of the operation, the problem is who and when to prepare the TPN
      while paying attention to the stability of multivitamins. Recently, a TPN kit
      that includes multivitamins and does not need a syringe or an injection needle to
      add vitamins to the TPN preparation was launched. Accordingly, we conducted a
      study to examine the simplicity of the procedure and usefulness of the product on
      the basis of time required to add other components to the TPN preparation, as
      assessed by questionnaire. The subjects of the study were medical care providers
      as well as patients on HPN and their families. The time required for TPN
      admixtures was significantly shorter compared with the conventional method.
      According to the questionnaire, the storability and easiness of the procedure
      were particularly highly appreciated. This product has the advantage that
      sterility can be maintained at home, that contamination with foreign bodies can
      be reduced, and that it can be stored at room temperature. Since it can be
      preserved in preparation for natural disasters and can be carried around during
      travel, it is expected to improve the QOL of patients on HPN and their families.

PMID- 14708312
TI  - [Development of an automatic measurement system of biological signals].
AB  - Recently, in-home treatment of hemodialysis has been focused on the enhancement
      of the quality of life (QOL) of patients. However, no medical staff monitors the
      treatment, and the family helpers have to take care of the patients during
      hemodialysis. Sometimes the patients themselves have to do it according to their
      circumstances. In order to reduce the burden placed on the patients and people
      around them, we are trying to develop a system for preliminary diagnosis of the
      patient's condition before the hemodialysis session, which estimates the
      condition of the patients and encourages a necessary treatment to them. In this
      paper, we describe an automatic measurement system of biological signals, which
      consists of two subsystems, a measurement system and a data collecting system.
      These subsystems are connected through wireless communication, allowing remote
      observation of patients' biological signals.

PMID- 14708313
TI  - [Frostbite due to accidental fall of a portable liquid oxygen device--report of a
      case].
AB  - We experienced a case of frostbite due to the accidental fall of a portable
      liquid oxygen device. We think this accident occurred because medical staff have
      little understanding of an oxygen device. We must use medical instruments safety.

PMID- 14708314
TI  - [Involvement of Daikou Sunabashi Clinic in home care to home death].
AB  - Daikou Sundabashi Clinic provides continuous advanced medical treatment and
      visiting nursing services for patients with serious diseases till their death at
      home. The clinic has been involved in home care of 72 patients in total during
      the period from April 2002 to July 1 of 2003. Of the patients, 40 patients died
      to date and 71% (32 patients) of them died at home. 49 of the 72 patients (70%)
      had terminal cancer and mostly required advanced home care. The clinic provides
      services according to the following principles till the death of the patients: 1.
      All of our medical staff pool their information and stay in very close
      communication with one another. 2. The attending physician gives a complete
      explanation of the patient's condition to his/her family. 3. The staffs respond
      to emergency calls around the clock using 2 cell phones. Under this very
      meticulous and fast-response system, seriously ill patient can receive continuous
      and high-quality treatment at home and die at home even if the family is not
      adequately capable of providing care.

PMID- 14708315
TI  - [Factors interfering with change to home care in the end of life].
AB  - We experienced 2 cases in which both the patients and their families hoped for
      home care and the medical staff thought it was possible; nevertheless, this could
      not be carried out in the end and the patients died in the hospital. We assessed
      the factors that prevented the change from hospital to home care based on the 7
      conditions necessary for home care described by Yamazaki. We confirmed that
      discrepancy between the patients and the medical staff regarding the timing for
      the change to home care was one of those factors. We found out that in the case
      of end-of-life care the will of the patient strongly influences the possibility
      to change to home care and that there is discrepancy between the patients and the
      medical staff regarding the timing for that change.

PMID- 14708316
TI  - [Usefulness of fentanyl patch in home palliative care].
AB  - Fentanyl patch (Durotep patch) is useful analgesic for terminal patients under
      home care, but the patients family may feel uneasy because they have to determine
      the induction dose, a prepare the rescue drug, and a variety of drug durability.

PMID- 14708317
TI  - [Pain control at home in cooperation with hospitals].
AB  - At present, many patients heavily dependent on medical care live at home.
      Therefore, the need for pain control at home is increasing. Within the limits of
      home care, the method used to control pain control is very important. Here we
      report 2 cases who need more than 1,000 mg of morphine (converted into oral
      administration). And we introduce our method for pain control at home. Our method
      is as follows: 1. Before the patient is discharged from the hospital, we go to
      the hospital and confirm the patient's condition and pain. 2. If necessary,
      before the patient is discharged from the hospital, we request to change
      instruments for home care. 3. We select the best way (instruments, circuits,
      administration) in consideration of the patients' or their families ADL. 4. When
      we change a route from oral administration to injection, we let the patient enter
      the hospital temporarily to adjust the quantity of morphine.

PMID- 14708318
TI  - [Review of our home parenteral nutrition (HPN) and home enteral nutrition (HEN)
      cases].
AB  - We reviewed our cases of HPN and HEN after percutaneous gastrostomy. We had 38
      patients (26 men, 12 women) on HPN. Of them, 23 (17 men, 6 women) had an
      implantable subcutaneous infusion port. The average age of HPN cases was 69
      (range 40-92) years, and 34 patients (89%) suffered from a malignant disease. The
      mean duration of HPN was 104 (range 2-543) days. Home anti-cancer chemotherapy
      was provided for 2 patients. Percutaneous gastrostomy was performed for 7
      patients (4 men, 3 women) by endoscopy (PEG, 6 cases) and 1 patient needed an
      open laparotomy. Their average age was 60 (range 40-83) years. 5 patients with a
      malignant disease who were in HPN underwent gastrostomy for decompression
      drainage of a digestive tract obstruction. 2 patients had a benign disease and
      were on HEN for a long time. We experienced 2 cases of skin complications, one
      under HPN and the other under HEN, but no severe complication experienced. HPN
      and HEN contribute to improve the patients' QOL.

PMID- 14708319
TI  - [Method for home parenteral nutrition (HPN) at Daikou Sunadabashi Clinic].
AB  - In recent years many patients who have become heavily dependent on medical care
      live at home. At Daikou Sunadabashi Clinic, we take care of many patients who
      have malignant tumors, at their homes. They need many medical treatments, so HPN
      has become a common practice. Here we show our circumstances of HPN. And we
      introduce our method for HPN. Our method is as follows: 1. Before the patient is
      discharged from the hospital, we go to the hospital and confirm the patient's
      condition. 2. We assess the level of training regarding HPN, and select the best
      way (instruments, circuits, administration) in consideration of the patients' or
      their families ADL. 3. We select a visiting nurse station 4. and train the
      visiting nurse in HPN using our manuals. 5. We use an HPN pump. 6. We select a
      simple way of infusion and adjust it to the patient's condition. In this way, we
      use HPN easily at home with the aid of a visiting nurse, visiting pharmacist,
      families, and us.

PMID- 14708320
TI  - [Survey on the attitude of families which have taken care of patients until their
      death at home].
AB  - The results of our survey using a questionnaire were as follows: 1. patients'
      families had a positive attitude toward the patients' death at home, 2. a good
      communication was established between the nurses from our institution and the
      patients or their families, 3. the nurses were considered reliable and friendly,
      4. for several days or immediately before the patients' death, which was the most
      severe period for the patients and their families, the patients and their
      families needed more support from the nurses.

PMID- 14708321
TI  - [A consideration through the support to resident diabetic patient and care
      giver].
AB  - Our hospital is a National General Hospital with 585 beds. We began the visiting
      care service from 1990 and four visiting staffs are working at present. The
      number of targets was 69 in 2002 including 32 patients over 70 years old and 20
      care-givers over 70 years old. Visiting care has been conducted to a 72-year-old
      female with diabetes since July 2000. The patient is in bedridden condition and
      at the beginning of visiting, she was taking oral medication but the condition
      was worsen by poor glycemic control and changed to insulin injection from June
      2002 after admission to the hospital repeatedly. The patient undergoes the
      measurement of blood sugar daily and takes meals with 1,200 to 1,400 kcal
      prepared by her husband. The care-giver is a 71-year-old husband. He was an "all
      work, no-play" type of person and had never done the housework, but he started to
      manage both housework and nursing because of bedridden of his wife. He is a
      reticent theorist, hates illogical behavior, and does not swayed by other
      opinions. He has accepted the things which need new knowledge and techniques such
      as measurement of blood glucose and insulin injection. However, for meals, he
      only bought side dishes and placed them. Care such as keeping the patient clean
      was in a same state. The patient consulted and admission to the hospital
      repeatedly because conditions were not stable. Visiting nurse supported daily
      life of patient and care-giver especially in nutrition instruction to continue
      home life. As the result, attitude and behavior toward nursing of care-giver were
      changed and the patient could continue home life. Therefore we reported here.

PMID- 14708322
TI  - [Preparation of pamphlets to teach the technique of home parenteral nutrition
      aiming at timely back home].
AB  - The home drip infusion is a stressful procedure for both patients and families
      under HPN at home. Effective and reliable guidance for drip infusion management
      should be provided while patients are still at the hospital to realize reliable
      home care. We revised the HPN Guidance Manual and report the process in this
      article. We revised the manual according to the principles that "the guidance is
      subdivided into 3 steps so that the contents of the guidance can be adjusted for
      individual patients", that "a lot of photos and illustrations for frequently used
      2 models are placed" and that "a video is prepared to make the most of the impact
      motion pictures can give". We want to use the manual in future clinical
      practices.

PMID- 14708323
TI  - [A new systemic combination chemotherapy to be provided at home for patients with
      unresectable recurrent colorectal cancer].
AB  - We compared the effectiveness of 5-FU + l-LV with CDDP + 5-FU as a systemic
      chemotherapy for unresectable recurrence of colorectal cancer. The protocol we
      carried out in one group was as follows: (Group 1) 5-FU 2,000 mg mixed with l-LV
      100-200 mg in the disposable balloon pump was administered continuously for 1
      week. In the other group, (Group 2) we administered CDDP 5 mg/day every 5 days
      for a week and continuous 5-FU 500 mg/day for 3 weeks in the hospital, and in the
      outpatient clinic CDDP 5 mg/day every 2 days for a week with UFT-E 300-600
      mg/day, orally, everyday. The response rate of Group 1 was 18.8% and that of
      Group 2 was 19.3%; the median survival time (MST) was 10.8 months for Group 1 and
      8.4 months for Group 2. There were no significant differences between the 2
      groups regarding these parameters. Hand foot syndrome (HFS) was observed in 43.8%
      of the patients, and stomatitis in 37.5% of all cases as adverse effect of
      systemic chemotherapy using 5-FU + l-LV. But the grade of the adverse effect was
      low and patients could continue with this systemic chemotherapy.

PMID- 14708324
TI  - [Chronic nephrotic syndrome as an example of nursing home care service].

PMID- 14708325
TI  - [Review of the factors which make diabetic home medical care difficult].
AB  - In the patients who were managed in the diabetes treatment department, 33
      patients were chosen as the difficult cases for the home medical care, and the
      factors were reviewed. As for the man and woman ratio, 11 were men and 22 were
      women. The number of female patients was twice larger. The average age was 81.7
      years old. As for the mode of the medical care, 11 patients were under the long
      term hospitalization, 1 was under care of the health care facility, 12 were under
      care of the nursing home, 5 lived in private facilities for senior citizens, and
      4 were treated under home medical care. The main reason to refuse the home
      medical care was the decline of the self-management ability. Of the 33 patients,
      dementia was observed in 21 patients, and the lack of recognition on their own
      disease was seen in 12 patients. So, without the support, the home medical care
      could not be provided. It is difficult to provide home medical care because of
      the complications (especially impaired visual sight, or cerebral vascular
      disease), the complexity of illness, the state of the family involved in home
      care, and the reform of the healthcare system. In order to promote the home the
      medical care of the elderly diabetics whose medical dependency became high, the
      management of the dementia patient, the support to the family involved in home
      care, the valid utilization of the care insurance system among other issues seems
      to be future challenges.

PMID- 14708326
TI  - [Usefulness of percutaneous endoscopic gastrostomy (PEG) in home health care-
      investigation from the viewpoint of cost effectiveness].
AB  - The use of percutaneous endoscopic gastrostomy (PEG) has widely spread in recent
      years, even in Japan. In our hospital, we have performed this procedure in over
      20 patients per year recently. In this study, we investigated the usefulness of
      PEG in home health care from the view point of cost effectiveness. We found that
      medical expenses decreased remarkably when patients underwent PEG because they
      could switch from hospital care to home health care, shortening there by the
      period of hospital care. The role of PEG in home health care will be more
      important also from cost effectiveness.

PMID- 14708327
TI  - [A case study of shifting a patient with percutaneous endoscopic gastrostomy
      (PEG) to home care].
AB  - We studied the primary factor preventing a patient with PEG from being
      transferred to home care focusing on the dietetic situation. The study has
      revealed differences in not the age of the patient, the days of hospitalization
      or hematological and biochemical test data but in the condition of use of home
      care services or family makeup. In other words, insufficient use of social
      resources is considered to prevent shifting to home care or continuation of home
      care of patients with PEG. It is necessary to understand not only dietetic
      situation but social backgrounds of patients and supply information.

PMID- 14708328
TI  - [EMI net--electronic medical record sharing in local community for home care
      medicine].
AB  - An electronic medical information network (EMI net) includes patient records from
      more than 40 facilities in Matsudo City and it is now used especially to improve
      the communication between doctors and nurses who visit patients' home. This fact
      suggests the importance of a medical information sharing system in a local area
      for home care medicine. An infrastructure connecting facilities to share the
      database of the patient records is essential for home care medicine performed by
      a multidisciplinary team beyond one medical facility.

PMID- 14708329
TI  - [Home medical care network in the community supporting hospital--nursing
      consultant acting for community coordination].
AB  - Tama Nambu-Chiiki Hospital is a secondary medical institution providing the acute
      short-term care centered on cancer treatment and emergency medical service, which
      few other medical institutions in the region provide. The hospital, which has no
      system to directly support home medical care by house visit or visiting nurses,
      needs to coordinate home medical care with other community medical institutions.
      2 nurses serve as the Nursing Consultants who provide consultation services over
      the issues related to home medical care and other issues face to face or by phone
      and coordinate home medical care with other community medical institutions.
      Medical coordination based on trust and understanding of home medical care by
      hospital staffs are essential for the smooth transfer to home medical care.
      Activities of the hospital are studied to cope with the changes in healthcare
      trend.

PMID- 14708330
TI  - [Present situation of home care and roles of nurses at Tokyo Women's Medical
      University Hospital--through the 5-year home care support activities].
AB  - Diseases, details of interventions, medical cares provided and the condition of
      use and services of local medical institutions were investigated in the home care
      support activities during the period from November 1997 to March 2003. We
      intervened in 1,309 patients. 70% of them were terminal patients with malignant
      tumor. Interventions were mostly consultations about the life under medical care,
      guidance about HPN/tube feeding, consultations about nursing and coordination
      with local medical institutions. 422 of them were under care of family doctors.
      502 of them used visiting nursing. 70% of the patients under care of the hospital
      required high-tech home care and home hospice care. The 5-year activities
      indicate that nurses who support home care at the hospitals providing acute
      medical care are expected to 1. serve as the consultation contact for patients
      and families, 2. support the life under medical care in consultation with
      internal and external related professionals, 3. use social resources, 4. serve as
      the contact for providing the logistic support under an emergent situation or
      under the lack of care-giving capabilities, 5. provide guidance for the safe use
      of high-tech home medical care by patients/families at the discharge, 6.
      communicate or coordinate with local medical institutions for continued
      care/nursing and 7. develop/support the flexible and convenient distribution
      system of medical equipment and medical materials/drugs or the 24-hour healthcare
      support system jointly with private enterprises.

PMID- 14708331
TI  - National Adult Cardiac Surgery Registry: past, present and future.
AB  - A task force commission was created with the support of the Portuguese Society
      for Cardiothoracic and Vascular Surgery with the aim of organizing a National
      Adult Cardiac Surgery Registry, collecting clinical data and types of cardiac
      surgical procedure performed in Portugal. Selected variables include risk
      factors, cardiac status, preoperative hemodynamics, surgical procedure, hospital
      stay and mortality. Information is collected into a database in each institution
      and sent via the internet to a central database responsible for grouping and data
      analysis. It is hoped that this National Registry, through standardized data
      collection, will provide information on cardiac surgery activity in Portugal and
      its risk adjusted results.

PMID- 14708333
TI  - Aortic coarctation.

PMID- 14708332
TI  - Patients with aortic coarctation operated during the first year of life,
      different surgical techniques and prognostic factors--21 years of experience.
AB  - The authors reviewed the clinical files of all patients with coarctation of the
      aorta (CoAo) operated during the first year of life, in a tertiary center, in
      order to assess the outcome of different surgical techniques and prognostic
      factors. MATERIAL AND METHODS: The study included all patients operated from 1
      June 1980 to 1 June 2001. They were divided into three groups according to
      diagnosis: Group I--isolated CoAo (with or without persistent ductus arteriosus
      (PDA), group II--CoAo plus ventricular septal defect (VSD), and group III--CoAo
      associated with complex heart defects. The surgical techniques were divided into
      four groups: Group A--resection of the CoAo with end-to-end anastomosis, group B-
      Waldhausen technique (subclavian flap), group C--enlargement of the aorta with a
      patch, and group D--Waldhausen technique plus resection of the CoAo with end-to
      end anastomosis. Several parameters were analyzed: sex, age at surgery, other
      surgical procedures during surgery, reoperation, mortality and outcome (good
      result, recoarctation). RESULTS: 156 patients were operated during the study
      period (84.5% of them since 1989). 61.5% were male. Surgery was performed between
      3 and 336 days of life. 60.9% patients were included in group I, 32.7% in group
      II and 6.4% in group III. 25.0% of the patients had group A surgery, 60.2% group
      B surgery, 7.0% group C surgery and 7.7% group D surgery. The PDA was sectioned
      in 48.0% of the patients. It was necessary to perform banding of the pulmonary
      artery, during the first surgery, in 19.9% of cases. 18.6% needed a second
      operation to close the VSD and for debanding or repair of associated defects.
      Total mortality was 19.2%. Mortality rate per groups was: Group I--15.8%, group
      II--21.5%, group III--30.0%, group A--18.0%, group B--19.1%, group C--27.2% and
      group D--16.7%. In 7.6% of the patients recoarctation was found during follow-up.
      40% of the patients are doing well with no medication and minor or no residual
      defects. 29.4% were lost to follow-up. CONCLUSIONS: Total mortality has decreased
      over the years with the highest mortality found in Group C and Group III. The
      best results were achieved in patients with isolated CoAo. Long-term results were
      generally good with few recoarctations and a good quality of life.

PMID- 14708334
TI  - Atrial septal closure in adults: surgery versus amplatzer--comparison of results.
AB  - OBJECTIVE: To compare the efficacy, safety and morbidity of surgical versus
      percutaneous atrial septal defect (ASD) closure. POPULATION AND METHODS: We
      studied all cases of ASD closure (surgical or percutaneous) performed in our
      hospital during the last 5 years. We analyzed the clinical and echocardiographic
      characteristics of both groups and compared the success rate of the procedure,
      events, days of hospital stay and evolution during the 1st year. RESULTS: 63
      patients (pts) with ostium secundum ASD were treated in our hospital in the last
      5 years; 25 (60% female) underwent surgery (A) while 38 (68% female) underwent
      percutaneous closure with an Amplatzer device (B); mean age was 38 (13-67) and 40
      years (15-72), respectively. Dyspnea and fatigue were the most frequent symptoms
      in both groups (57% A; 29% B), while the most frequent signs were fixed splitting
      of S2 (78% A; 88% B) and systolic murmur at the left sternal border (82% A; 87%
      B). Previous ECG presented incomplete right bundle branch block in 63% of both
      groups. The size of the ASDs, as well as Qp:Qs, were greater in the surgical
      group: 24.6 (5-50) vs. 18.97 mm and 3.1 (1.5-6.5) vs. 2.7 (1.2-5.2) respectively.
      Right cardiac chambers were enlarged in 92% of pts in A vs. 84% in B. Paradoxical
      interventricular septal motion (PSM) was present in 78% of pts in A and 67% in B.
      The success rate (100%) was similar in both groups but immediate minor events
      were more frequent in A (28 vs. 13%). Duration of hospital stay was longer in A:
      5.4 days (3-9) vs. 1.5 days (1-4). Normalization of right cardiac chamber
      diameter was faster in B: 73% in the 1st control echocardiogram (at 0-64 days,
      mean 29) vs. 60% in A, performed at a later stage (45-455 days after the
      procedure, mean 155). At the time of reassessment PSM was still present in all
      the pts of group A and in only 10% of B (p < 0.0001). CONCLUSIONS: The success
      rate of ASD closure is 100% with both procedures and complications are rare. The
      percutaneous technique, however, permits a shorter hospital stay, involves less
      morbidity, and, despite sample limitations, seems to be associated with faster
      anatomical recovery. Therefore, in our opinion, surgical treatment should be
      reserved for those cases in which closure with an Amplatzer device is not
      technically or anatomically possible.

PMID- 14708335
TI  - Relation between hypertension and cardiovascular events--implications for
      coronary prevention.
AB  - OBJECTIVE: To study the relation between hypertension and cardiovascular events-
      stroke, myocardial infarction (MI), heart failure (HF), and chronic renal failure
      (CRF)--and to define implications for cardiovascular disease prevention. DESIGN:
      Cross-sectional study, in two stages, but with retrospective information about
      major cardiovascular events. SETTING: Primary care health centers (Lisbon
      Regional Health Administration). MATERIAL AND METHODS:  PARTICIPANTS: 3228
      patients, 1100 male (439 aged up to 60 years and 661 aged 60 years) and 2128
      females (860 aged up to 60 years and 1268 aged 60 years). The study covered
      stroke, myocardial infarction, heart failure, chronic renal failure with co
      variables of age, gender, body mass index (BMI), blood pressure, heart rate,
      antihypertensives, diabetes, total cholesterol, dyslipidemic therapy, and
      smoking. The group without hypertension (normotensives) and hypertensives-
      treated with antihypertensives and/or with systolic/diastolic blood pressure > or
      = 140/90 mmHg (n = 2169)--were compared, using logistic regression, to identify
      nonfatal cardiovascular complications associated with hypertension. Forward
      conditional logistic regression was used to test the multivariate models. The
      level of significance was taken to be 5%. The statistical packages Stata and SPSS
      were used. RESULTS: The analysis included 2839 cases (389 missing). The absolute
      frequencies of categorical variables were: smoking (n = 343); stroke (n = 150);
      myocardial infarction (n = 90); heart failure (n = 174); renal failure (n = 34);
      hypercholesterolemia (n = 864); diabetes (n = 375); male gender (n = 976) and
      female gender (n = 1863). The regression equation included the following factors:
      age (p < 0.001; OR = 1.068 and 95% CI 1061-1.075); body weight (p = 0.001; OR =
      1.020 and 95% CI 1.008-1.032); stroke (p = 0.007; OR = 2.523 and 95% CI 1.286
      4.951); HF (p = 0.013; OR = 2.449 and 95% CI 1.205-4.979); diabetes (p < 0.001;
      OR = 1.894 and 95% CI 1.328-2.701); hypercholesterolemia (p < 0.001; OR = 1.693
      and 95% CI 1.350-2.123); and BMI (p < 0.001; OR = 1.006 and 95% CI 1.003-1.010).
      CONCLUSIONS: Nonfatal stroke was associated with hypertension, as was heart
      failure, but neither nonfatal myocardial infarction nor chronic renal failure
      were. Control of hypertension is therefore expected to be more efficacious in
      reducing cerebrovascular events than those caused by coronary heart disease.

PMID- 14708336
TI  - Aortic dissection surgery: experience of 78 cases.
AB  - From May 1990 to January 2001, 78 patients underwent surgery for aortic
      dissection, 68 (87%) of type A. Presentation was acute in 55 patients (71%). For
      type A dissection, in-hospital mortality was 13% (9 patients) and late mortality
      was 16%. For type B dissection, in-hospital and late mortality were both 30% (3
      patients). The follow-up was complete and medical and imaging controls were
      performed periodically. Computerized axial tomography has shown persistence of
      distal aortic dissection in 18 patients, one of whom maintained dissection of the
      supraaortic trunks with false lumen thrombosis. Six patients maintained signs of
      dissection in the thoracic and abdominal aorta with patent false lumen. In
      another eight patients the false lumen was thrombosed. In 3 cases the dissection
      was located in the abdominal aorta. Two patients developed pseudoaneurysms of the
      thoracic aorta, one of whom was reoperated due to symptoms of dysphagia and chest
      pain, with angiographic signs of probable rupture of the aorta. Periodic imaging
      monitoring is essential, as it allows assessment of the extent of residual aortic
      disease and its evolution, with early detection of possible complications. This
      will enable prompt and safe action in those patients who may benefit from
      reoperation.

PMID- 14708337
TI  - Cervical aortic arch and 22q11 deletion--the role of MRI in diagnosis.
AB  - Aortic arch anomalies are relatively common, occurring in 0.5-3% of the
      population. In recent years, they have been recognized as being among the
      cardiovascular malformations found in chromosome 22q11 deletion. MRI is now an
      alternative method of diagnosing aortic arch anomalies since it accurately
      defines aortic anatomy and its relation with the trachea and esophagus, with some
      advantages in comparison with echocardiography and conventional angiography. The
      authors present two cases of cervical aortic arch and VSD associated with
      DiGeorge syndrome (CATCH22+), diagnosed by conventional angiography and magnetic
      resonance imaging, respectively.

PMID- 14708338
TI  - Composite outcomes in clinical trials: uses and problems.
AB  - Randomized clinical trials are the gold standard for proof of efficacy of a
      therapeutic or preventive intervention, because their design is the only one
      capable of establishing causation in medicine. Today drug licensing is based on
      RCTs that have shown improvement in patients' symptoms, prognosis or both. One of
      the most crucial steps in RCT planning is selection of the main outcome measures.
      These are normally classified as primary and secondary outcomes. The primary
      outcome is very important, since it constitutes the main basis for claiming
      efficacy in an RCT, so its choice and use must be particularly rigorous.
      Composite outcomes have become increasingly common in the medical literature.
      Even trials with a single primary outcome usually have several secondary ones
      (composite). Composite outcomes present several potential problems: clinical
      endpoints must be relevant and significant in terms of patient prognosis, and so
      non-validated surrogate endpoints should not be used; they must be carefully
      defined, should not be excessive in number, and, when they include all-cause
      mortality, should be carefully constructed. In this article we present and
      discuss the uses and problems of composite outcomes in RCTs.

PMID- 14708339
TI  - Different atrial septal defects: different transcatheter occluder devices.

PMID- 14708340
TI  - [Incidence and prevalence of hypercholesterolemia in Portugal].

PMID- 14708341
TI  - [Cellular lipid dynamics].
AB  - During the past years, the notion of microdomains at the surface of cellular
      membranes has been developed. These are constituted by lipid rafts which involve
      sphingoglycolipids and cholesterol. To these rafts are associated proteins which
      have a lipid anchor or are transmembrane proteins. These lipid rafts target
      specific proteins at the plasma membrane surface and can remain associated with
      them. They are present in surface receptors and endocytosis occurs upon binding
      of the specific ligands. Thus these rafts participate to major aspects of
      cellular dynamics. These rafts are complex structures, insoluble in non-ionic
      detergents. According to the detergent used, many types of rafts can be isolated.
      Any alteration of cholesterol, sphingoglycolipids, or abnormalities of the
      proteins themselves, can lead to abnormal targeting at the membrane surface. It
      is possible that specific sphingoglycolipids are necessary to target specific
      proteins at the membrane surface. This may explain the complexity of the
      sphingoglycolipid molecules, both in relation to their oligosaccharide and to
      their ceramide structures. There is both a cellular and a tissue specificity of
      these constituents. Complex sphingoglycolipids are involved in cellular
      differentiation, cellular polarization, and modified in relation to cancer. Virus
      and bacteria can be linked to the sphingoglycolipids of these microdomains and
      alter cellular signaling and function. Sphingoglycolipids are involved in
      autoimmune diseases as antibody targets and in neurolipidoses which are genetic
      diseases involving their catabolism. The dynamics of the lipid rafts, in relation
      to cholesterol, can be altered in Niemann-Pick's disease type C and in
      Alzheimer's disease. Thus these microdomains are involved in many aspects related
      to normal and pathological cellular dynamics.

PMID- 14708342
TI  - [Mechanisms of sorting and transport of proteins to tw membrane domains of
      epithelial cells].
AB  - Polarity is a fundamental characteristic of most eukaryotic cells. The plasma
      membrane of such cells consists in two structurally and functionally different
      domains, i.e., the basolateral and the apical membrane, separated by tight
      junctions. The generation of the distinct molecular identity of both domains and
      its maintenance in spite of the dynamics of lipids and proteins at either surface
      requires sophisticated sorting and trafficking mechanisms. Recent progress in the
      field of polarized trafficking reveals that, for a detailed understanding of its
      mechanism and regulation, an integrated approach that includes the flow of both
      lipids and proteins is imperative. In this review, some recent progress in
      understanding mechanisms involved in protein sorting and trafficking is
      discussed. We focus on the role of lipid microdomains (Rafts) in trafficking of
      proteins to the apical surface of polarized cells.

PMID- 14708343
TI  - [Sphingolipid-mediated apoptotic signaling pathways].
AB  - Various sphingolipids are being viewed as bioactive molecules and/or second
      messengers. Among them, ceramide (or N-acylsphingosine) and sphingosine generally
      behave as pro-apoptotic mediators. Indeed, ceramide mediates the death signal
      initiated by numerous stress agents which either stimulate its de novo synthesis
      or activate sphingomyelinases that release ceramide from sphingomyelin. For
      instance, the early generation of ceramide promoted by TNF is mediated by a
      neutral sphingomyelinase the activity of which is regulated by the FAN adaptor
      protein, thereby controlling caspase activation and the cell death programme. In
      addition, the activity of this neutral sphingomyelinase is negatively modulated
      by caveolin, a major constituent of some membrane microdomains. The enzyme
      sphingosine kinase also plays a crucial role in apoptosis signalling by
      regulating the intracellular levels of two sphingolipids having opposite effects,
      namely the pro-apoptotic sphingosine and the anti-apoptotic sphingosine 1
      phosphate molecule. Ceramide and sphingosine metabolism therefore appears as a
      pivotal regulatory pathway in the determination of cell fate.

PMID- 14708344
TI  - [Lipid rafts, flotillin-1 and Alzheimer disease].
AB  - A beta peptide accumulates in the extracellular space during Alzheimer's disease.
      It is the cleavage product of APP (Amyloid Precursor Protein), a large
      transmembrane protein. After ultracentrifugation, APP is found in a low-density
      fraction, enriched in cholesterol. These properties are characteristic of lipid
      rafts, which are microdomains that "float" like rafts on the plasma membrane. We
      have confirmed the presence of cholesterol in the core of the senile plaque,
      using the fluorescent probe filipin. In addition, we have shown that flotillin-1,
      a marker of rafts, accumulated in lysosomes of neurons in Alzheimer's disease. In
      most cases (76% of the flotillin-1 positive neurons), the accumulation was
      associated with the presence of neurofibrillary tangles. Our data suggest that
      the A beta peptide, which is poorly soluble in water, is actually linked with
      cholesterol, possibly from cellular membranes, in the extracellular space.

PMID- 14708345
TI  - [Functional specificity of T-type calcium channels and their roles in neuronal
      differentiation].
AB  - Calcium plays a central role in cell signaling and T-type calcium channels
      constitute a unique route for the entry of calcium ions in excitable cells. The
      genuine electrophysiological properties of T-type calcium channels include
      activation at low voltages and window currents in the range of cell membrane
      resting potential. T-type channels therefore generate a specific calcium influx
      likely to play an important role during early stages of development, in various
      cellular functions including cell proliferation, cell differentiation, gene
      transcription and hormone secretion. Such T-channel activities are also
      associated with several pathological situations. With the recent cloning of three
      T-type pore channel subunits, alpha 1G, alpha 1H and alpha 1I (also called
      Cav3.1, Cav3.2 and Cav3.3, respectively), it has become possible to investigate
      further the role of T-type channels in various cellular functions, including
      neuronal differentiation. Here we describe recent data obtained in our laboratory
      demonstrating how T-type channels generated by the alpha 1H subunit contribute to
      neuronal differentiation.

PMID- 14708346
TI  - [The TRP family of channels: a complex gallery of characters].
AB  - Calcium influxes are of fundamental importance in eukaryotic cell functions.
      These calcium influxes are carried by different classes of membrane proteins that
      allow regulated calcium entry. If in excitable cells, such as neurones or muscle,
      voltage-dependent calcium channels represent the main source of calcium influx,
      other proteins are needed to assume such a function in non-excitable cells. In
      these, a sustained calcium influx is observed, secondary to phospholipase C
      activation, IP3 synthesis and internal calcium release. The identity of proteins
      implicated in this second messenger calcium-driven influx, as well as the
      mechanisms of activation of these channels have long been debated. In recent
      years, genes encoding a new kind of cationic channels called TRP channels have
      been identified. This molecular work has set the basis for further functional
      studies and helped to gain crucial information on the mechanisms by which
      extracellular calcium can penetrate into non-excitable cells. This review will
      present the most recent advances obtained on the molecular diversity of TRP
      channels and their mode of gating.

PMID- 14708347
TI  - [Role of L-type calcium channels in the calcium response and interleukin 4 (IL-4)
      synthesis by Th2 lymphocytes]].
AB  - CD4+ T lymphocytes are divided in Th1 cells that produce interferon (IFN) gamma
      and Th2 cells that synthesize IL-4. These subsets may arise from a common
      precursor: a combination of IL-12 plus anti-IL-4 monoclonal antibody (mAb) drives
      Th1 cell differentiation while IL-4 plus anti-IFN gamma mAb favor Th2 cell
      development. TCR stimulation activates protein kinase C that controls a calcium
      entry through L type calcium channels in Th2 cells. L type calcium channels are
      induced during Th2 but not Th1 cell differentiation. In addition, L type calcium
      channel inhibitors may be successfully used in the treatment of an experimental
      model of Th2 cell-mediated immunopathology. Thus, this signaling pathway that
      characterizes Th2 cells can be a target for the treatment of Th2 diseases.

PMID- 14708348
TI  - [HIV-1 Tat induces TNF-alpha production by human monocytes: involvement of
      calcium and PKC pathways].
AB  - In this study we investigated the signaling pathways triggered by Tat in human
      monocyte to induce TNF-alpha. In monocytes, calcium, PKA, and PKC pathways are
      highly implicated in the expression of cytokine genes. Our data show that (i)
      extracellular calcium is required for the calcium signal initiated by Tat in the
      monocyte and is required for TNF-alpha production, PKC pathway is also required,
      whereas the PKA pathway does not seem to be involved (ii) downstream from PKC,
      activation of NF kappa B is essential while ERK1/2 MAP kinases, even though
      activated by Tat, are not directly involved in the pathway signaling leading to
      TNF-alpha production.

PMID- 14708349
TI  - [Olfactory perception and learning in the honey bee (Apis mellifera): calcium
      imaging in the antenna lobe].
AB  - Honey bees are a key-model in the study of learning and memory, because they show
      considerable learning abilities, their brain is well described and is accessible
      to a wide range of physiological recordings and treatments. We use in vivo
      calcium imaging to study olfactory perception in the bee brain, and combine this
      method to appetitive olfactory conditioning to unravel the neural substrates of
      olfactory learning. Odours are detected by receptor neurons on the antennae. Each
      receptor neuron projects to the first-order neuropile of the olfactory pathway,
      the antennal lobe, connecting to projection neurons in one of its 160 functional
      units, the glomeruli. In calcium imaging experiments, each odour elicits a
      particular activity pattern of antennal lobe glomeruli, according to a code
      conserved between individuals. The antennal lobe is also a site where the
      olfactory memory is formed. Using optical imaging, two studies have shown
      modulations of odour representation in the antennal lobe after learning, with
      different effects depending on the type of conditioning used. While simple
      differential conditioning (A + B- training) showed an increased calcium response
      to the reinforced odour, side-specific conditioning (A + B-/B + A- training)
      decorrelated the calcium responses of odours between brain sides. This difference
      may owe to the formation of different memories, which will be addressed in future
      work. By specifically staining antennal lobe neuronal subpopulations, we hope to
      be able in the future to study synaptic plasticity in the honey bee.

PMID- 14708350
TI  - [xMLP is an early response calcium target gene in neural determination in Xenopus
      laevis].
AB  - In vertebrates, neural induction occurs during gastrulation when ectodermal cells
      choose between two fates, neural and epidermal. In Xenopus, neural induction has
      been regarded as a default pathway as it occurs, in dorsal ectoderm, when
      ventralizing signals (mainly Bone Morphogenesis Proteins, BMPs, potent epidermal
      inducers) are inhibited by dorsalizing signals, including factors such as noggin,
      chordin, and follistatin. However, our previous studies demonstrated that an
      instructive signal triggered by the activation of L-type voltage-sensitive
      calcium channels, resulting in a transient increase in intracellular free
      calcium, appears to be a necessary and sufficient requirement to induce the
      competent ectoderm toward the neural pathway. Here we further explore the
      relationship between the Ca2+ transient signals observed and the expression of
      early neural genes. We have performed a subtractive approach to identify the
      genes which are transcribed early after the calcium signal and involved in neural
      determination. We have analyzed a candidate gene (xMLP) which encodes a MARCKS
      like protein, a substrate for PKC. We show that this gene is activated by a
      calcium transient signals and induced by noggin overexpression. xMLP is expressed
      at the right time in presumptive neural territories. The putative role of xMLP in
      the process of neural induction is discussed.

PMID- 14708351
TI  - [Luminous plant and animals or the expression of aequorin and "chameleon" probes:
      a new light in calcium signaling].
AB  - Calcium ion is a universal second messenger in numerous cell physiological
      processes. The paper describes the structure and the activation mechanisms of the
      bioluminescent (aequorin) and fluorescent based GFP calcium sensitive probes
      (Cameleon) and the data obtained with such probes in genetically transformed
      animal and vegetal organisms. The importance of these in vivo Ca2+ imaging
      molecules in the understanding of calcium signalling is discussed.

PMID- 14708352
TI  - [Calcium and electropermeabilized cells].
AB  - Trains of short and intense electric pulses may induce a reversible local
      permeabilization on the membrane of the treated cells. Hydrophilic species can
      then almost freely cross the envelope and either enter or escape from the
      cytoplasm. The purpose of the present study was to investigate the possibility of
      introducing well defined amounts of Ca2+ ions within the cell. Chinese hamster
      ovary cells were used as a model system. When the pulsing buffer contained high
      levels of free Ca2+, the survival of cells was strongly affected. A 1 mM level
      was well tolerated. When cells were pulsed under moderated field conditions, it
      was observed that Ca2+ entered cells very rapidly (second time range). But the
      basic cytoplasmic level was set back spontaneously within a few minutes. The
      perspectives of this electrical injection are discussed for basic cell biology
      and high-throughput biotechnology.

PMID- 14708353
TI  - [Synthesis of functionalized cyanines. Fluorescence properties following
      complexation of cations].
AB  - The ionophoric properties of podands containing dioxazaphosphocane moieties
      linked by inactive spacers were studied. To increase the detection sensibility of
      these compounds we introduced a cyanine as spacer. Fluorescence analysis
      demonstrated the interest of cyanines as active spacers since the complexation by
      cations as Ca2+ and Mg2+ gives an enhancement of the emission intensity.

PMID- 14708354
TI  - [Unilateral facial paralysis and keratitis sicca, signs of temporohyoid
      osteoarthropathy in the horse].
AB  - A 9-year-old Dutch Warmblood mare was presented with a history of abnormal
      behaviour and acute facial nerve paralysis on the left side. Clinical examination
      revealed a slight head tilt and a corneal ulcer of the left eye. The base of the
      left ear was warm and painful. Endoscopic examination of the left guttural pouch
      showed thickening of the proximal part of the stylohyoid bone. Computer
      tomography revealed a left-sided prominent bony enlargement of the middle and
      proximal part of the stylohyoid bone and the tympanic bulla, fusion of the
      temporrhoid joint, and osseous proliferation of the pars petrosa of the temporal
      bone. The diagnosis was confirmed postmortem. The literature concerning the
      anatomy, clinical signs, and therapy of temporrhoid osteoarthropathy is
      discussed.

PMID- 14708355
TI  - [A cesarean section with tails].

PMID- 14708356
TI  - [The economical health of veterinary practices: funded charges for small animal
      practices].

PMID- 14708357
TI  - [RIP-DAP in the veterinary clinic].

PMID- 14708358
TI  - [Veterinary clinic Eibergen sets up a system of structural company management.
      Translating from work per item to work per hour].

PMID- 14708359
TI  - [(How) do I choose a external management advisor. External support begins with a
      project plan and an offer].

PMID- 14708360
TI  - [Veterinary public health].

PMID- 14708361
TI  - [Health claims in dog and cat feed].
AB  - The number and diversity of health claims for dog and cat foods have increased
      markedly over the past few years. There is no explicit legislation as to these
      claims. Many claims are insufficiently supported by research and are vague and
      suggestive. In order to inform pet owners and veterinarians properly and to
      enhance honest competition among pet food producers, rules for the application of
      claims should be developed. For the time being, the veterinarian will have to
      take a stand by critical assessment.

PMID- 14708362
TI  - [High hormone levels during the GGG (Group Veterinary Medicine for Small Animals)
      Autumn Meeting about treatment].

PMID- 14708363
TI  - [Insulin resistance as an inhibition of intake of the saturated fatty acids in
      form of triglycerides by myocyte receptors].

PMID- 14708364
TI  - [The content of double bonds and lipids in blood serum of healthy people and
      patients with hyperlipidemia].
AB  - The number of dual bonds (DB) was determined by the ozonization method in the
      lipid fraction of blood serm (BS) in healthy subjects and in patients with
      hyperlipidemia (HLP). Single-direction changes were detected in the DB quantity
      and in the lipid level in case of HLP; besides, a highly reliable positive
      correlation was established between the DB concentration and the basic BS lipid
      classes. The results suggest that an increasing DB quantity in HLP is
      preconditioned by a growing lipid contents and show their tense relation with
      components of the lipid transport system (LTS). The determination of the DB
      concentration, as of an index of the total unsaturation of the BS lipid fraction,
      provides for obtaining extra data useful in describing the LTS in different-type
      impairments of lipid metabolism.

PMID- 14708365
TI  - [The use of insulin-modified intravenous glucose tolerance test in the diagnosis
      of insulin resistance in patients with metabolic syndrome].
AB  - Fifty-five patients (mean age 42.3) with clinical signs of metabolic syndrome
      were investigated. The peroral glucose-tolerance and insulin-modified intravenous
      glucose-tolerance tests were used in the diagnosis of insulin-resistance.
      According to the SI index, a lower tissue sensitivity to insulin was detected in
      48 (87%) of patients; it is noteworthy, that a low SI index was registered in
      some of them, when indirect signs of insulin-resistance, like hyperglycemia,
      hyperinsulinemia, were absent.

PMID- 14708366
TI  - [The lipid composition of high-density lipoproteins in patients with psoriasis].
AB  - Ten lipid fractions were detected in patients with psoriasis by the method of
      unidimensional chromatography in a thin layer of silica gel with two solvent
      systems designed for separating a lipid extract of high-density lipoproteins
      (HDLP). Four phospholipids fractions were identified as follows: three main ones,
      i.e. phosphatidylcholine, lisophosphatidylcholine and sphyngomielin, and one
      minor fraction, i.e. phosphatidylethanolamine. The HDLP lipid comprises free
      cholesterol and its esters. Three glyceride fractions were detected: mono-, di-
      and triglicerides and free fatty acids. The ratio of the individual phospholipid
      fractions, on the one hand, and of free to ester-bound cholesterol was found in
      HDLP by computer-aided densitometry of chromatograms and coincided with the
      routinely obtained data. The described method designed to evaluate the HDLP lipid
      composition can be handy in investigations of HDLP in patients with psoriasis.

PMID- 14708367
TI  - [The methodological specificity of PCR-test of gene p53 in plasma and blood cell
      DNA of oncological patients].
AB  - The evaluation of mutations in the p53 gene is of a big value for the laboratory
      diagnostics in oncology. The p53 gene was analyzed, within the present case
      study, in blood plasma, in which tumor-origin DNAs were detected, as well as in
      blood cells and in tumor tissue. Optimal conditions were defined for polymerase
      chain reaction (PCR) with primers. The adequacy of the conditions selected for
      PCR and for SSCP-electrophoresis, when used in the analysis of mutations in exons
      5-8, gene p53, was shown by the method of direct sequencing. The first results on
      revealing the frequency of gene-p53 mutations were obtained for some of the
      oncology diseases in the studied population.

PMID- 14708368
TI  - [Physical and chemical properties of the condensate of breathed-out air in
      healthy people].
AB  - The physical-and-chemical condition of condensate of breathed-out moisture (CBM)
      was studied by the computer-aided analysis of axis-symmetric drops' form in
      healthy subjects; such condition was found to depend on sex, age and smoking
      addiction of the examined persons. The surface tension of the mentioned moisture
      correlated with its viscoelastic index and with relaxation. The metabolites of
      nitric oxide, lipids, urea, lactic acid (not uric acid) and of hydrogen peroxide
      were found to influence the physical-and-chemical parameters of respiratory
      moisture. Hydrogen peroxide had a reverse correlation with the CBM viscoelastic
      module. A status of the pulmonary surfactant can be evaluated by using the
      studied physical-and-chemical CBM parameters.

PMID- 14708369
TI  - [The hierarchical approach to the system of medical laboratory tests (lecture)].

PMID- 14708370
TI  - [Immunophenotyping in diagnosis of chronic lymphoproliferative diseases].
AB  - With due respect to their many-year experience, the authors focused their
      attention on the peculiarities of implementation and registration aspects of the
      immunofluorescence method of immunotyping made in cell suspensions and in tissue
      imprints; additionally they made a system of a set of monoclonal antibodies (used
      for the purpose), which enable the differential diagnosis of reactive conditions
      related with various malignant lymphoproliferative diseases (LPD). It order to
      specify a nature of lymphoid cells it is suggested to undertake the
      immunophenotyping withing a gradually expanding set of monoclonal antibodies,
      which reflects different parameters of lymphoid cells like linear attributes,
      clonal characteristics, differential-diagnostic markers, functional status and
      proliferative activity. Typical marker phenotypes of lymphoid cells observed in
      the main B- and T-cell LPDs are described; a possibility is mentioned that there
      can be errors in interpreting the phenotyping results while diagnosing an LPD.

PMID- 14708371
TI  - [Immunological monitoring of bone tissue resorption following endoprosthesis of
      large joints].
AB  - There was noted a reaction of the immune system to big-joint replacements, which
      developed both as a stereotype acute-phase response to the surgical intervention
      and a moderate immunosuppression, and as a response to the functioning of the
      implant (beginning from month 6 after surgery), when a mild phagocytes' activity
      and moderate changes in the acute-phase proteins were registered. Later, the
      monocyte-lymphocyte reaction of blood involving a higher production of
      osteoresorptive IL-1 and TNF were observed during the shaping resorption of
      osseous tissue. Complications can be prognosticated on the basis of the below:
      contents of leukocytes' main populations; activity of cytoplasm cation proteins;
      and concentration of the main classes of immunoglobulins and of IL-1.

PMID- 14708372
TI  - [Diagnostic value of the radioimmunoassay and immunoenzyme assay in analysis of
      HBsAg in children with viral hepatitis].
AB  - The purpose of the case study was to evaluate the diagnostic efficiency of
      radioimmunoassay (RIA) and of immune-enzyme assay (IEA) in indicating the HBsAg
      in the blood of children with viral hepatitis. The study was based on a
      simultaneous indication of HBsAg by RIA and IEA in 98 samples of blood serum
      (plasma). It was shown that both assays are practically univocal in as far as the
      HBsAg indication within the mentioned circumstances is concerned.

PMID- 14708373
TI  - [Development of a competitive immunoassay based on monoclonal antibodies for the
      detection of specific antibodies to pseudotuberculosis pathogen].
AB  - A highly sensitive, effective and rapid method--a competitive alternative to
      ELISA--was developed for the detection of specific antibodies to Y.
      pseudotuberculosis. It is based on monoclonal antibodies (MAbs) recognizing the
      species- or serogroup specific epitopes of Y. pseudotuberculosis. The competitive
      ELISA was used in testing the murine hyperimmune sera and human antisera sampled
      from patients with different infectious intestinal diseases including several
      cases of pseudotuberculosis. The use of the MAbs-based ELISA in the laboratory
      diagnostics of pseudotuberculosis is under discussion.

PMID- 14708374
TI  - [The specificity of interaction between the complement and the lipopolysaccharide
      with a low activity of the complement (hypothesis)].
AB  - Interactions between the complement with a low activity and the lipopolysacharide
      (LPS) with an extensive concentration range were experimentally investigated in
      vitro. A model was suggested that provides an explanation to the concentration
      related dependence. The complement and LPS were shown, under certain conditions,
      to form the membrane-attacking complexes, which are not bound with the bacterium
      membrane and which can lyse any cells. Damages made by the above complexes to
      endothelial cells of the vessels could result in the onset of the syndrome of
      disseminated intravascular coagulation (DIC). The results can be used to develop
      a method applicable to evaluating a concentration of endotoxin and to creating
      anti-tumor drugs.

PMID- 14708375
TI  - [Necessity of advancing the leukograms of clinical blood test and its technical
      possibilities].

PMID- 14708376
TI  - [Selective agar for isolation of enteropathogenic Yersinia in the course of
      routine bacteriological examination].

PMID- 14708377
TI  - [Organ transplantation status in Denmark].

PMID- 14708378
TI  - [Complications of immunosuppressive therapy in organ transplantation].

PMID- 14708379
TI  - [Ten years' experiences with heart transplantation at Skejby hospital].

PMID- 14708380
TI  - [Transplantation of lungs from non-heart-beating donors].

PMID- 14708381
TI  - [Thorax transplantations--Rigshospitalet 1990-2002. The first 500 heart, lung and
      heart-lung transplantations].

PMID- 14708382
TI  - [Liver transplantation in Denmark].

PMID- 14708383
TI  - [Pancreas transplantation].

PMID- 14708384
TI  - [Kidney transplantation].

PMID- 14708385
TI  - [Small-bowel transplantation].

PMID- 14708386
TI  - [Xenotransplantation].

PMID- 14708387
TI  - [Urogynecology in USA. Report from a visit to Loyola University, Chicago and
      Scott&White Clinic, Texas].

PMID- 14708389
TI  - [At last free from the evil rays].

PMID- 14708388
TI  - [The good rays?].

PMID- 14708390
TI  - [Where is the National Board of Health and Welfare?].

PMID- 14708391
TI  - [Increased speed=more killed].

PMID- 14708392
TI  - HIV/AIDS, sexual and reproductive health: intimately related.

PMID- 14708393
TI  - Men and women--still far apart on HIV/AIDS.
AB  - What could be more logical than a gay-feminist alliance to respond to the AIDS
      epidemic in Latin America? However, drawing on published articles and the
      author's experience in HIV/AIDS work in Chile, this paper argues that such an
      alliance is more rhetorical than real. Instead, both groups tend to stick to
      their respective niches and view the epidemic through the prism of the particular
      needs and concerns of their target constituencies, rather than learn from and
      support each other. Feminist rhetoric sometimes suggests that AIDS is a problem
      only because it affects women. The African paradigm of vulnerable women is
      inexactly applied, given the predominantly male and homosexual nature of the
      epidemic in most Latin American countries. Both women and homosexually active men
      are highly vulnerable to HIV infection, and little is gained by competing for the
      top slot on the "tragedy honour roll". Latin American gay men's groups, torn
      between AIDS and gay rights activism, often resist both protagonism by women and
      women's issues. Although the fight for access to antiretroviral treatment has
      obscured this conflict, it resurfaces in associations of HIV-positive people and
      may increase along with heterosexual transmission in the region. Discussion and
      exchanges should be encouraged to overcome these largely hidden divisions.

PMID- 14708394
TI  - Some considerations on sexuality and gender in the context of AIDS.
AB  - Gender has become a major conceptual tool for understanding the evolving HIV
      pandemic globally. As such, it has provided a powerful way to see the structure
      of relations between men and women as central to various epidemics, and added
      weight to our understanding of HIV infection as not simply an individual
      experience of disease. Yet, as a concept, gender has its blind spots. This paper
      argues that there are four issues central to our understanding of how the HIV
      pandemic moves and develops that are not necessarily best understood through an
      analysis that uses gender alone, namely: women's vulnerability, men's
      culpability, young people's sexual interests and marginalized sexual cultures.
      The paper proposes using sexuality as a framework for analysing these issues and
      seeks to utilise developments in critical sexuality research to add to gender as
      a way to increase the capacity to respond to the HIV/AIDS crisis.

PMID- 14708395
TI  - HIV/AIDS in the shadows of reproductive health interventions.
AB  - In December 1999, the Tanzanian president declared HIV/AIDS a national disaster.
      By the time the National Policy on HIV/AIDS was released in 2001, an estimated
      750,000 women of reproductive age were infected. Yet in spite of the impact of
      HIV on reproductive health, AIDS and reproductive health programmes are still
      thought of and implemented through separate channels, to the detriment of both.
      However, although AIDS remains in the shadows of reproductive health
      interventions, the lack of AIDS talk does not lessen the impact of the disease on
      people's lives. During the course of my participant observations in maternal and
      child health/family planning (MCH/FP) clinics collected during 25 months of
      fieldwork in 10 clinics in Morogoro, Ruvuma and Kilimanjaro Regions, I rarely
      heard about AIDS. This article attempts to analyse why. Historically competing
      bureaucracies in MCH/FP and gender and development are not easily unified with a
      vertical HIV/AIDS control programme under the umbrella of "reproductive health".
      HIV/AIDS cannot merely be inserted into existing family planning programmes, re
      named "reproductive health" programmes. As the AIDS epidemic is transformed
      through new technologies, reproductive health policy and priorities will be
      called into question and force us to look at the state of the African health care
      system, networks of care-giving, and how individuals and communities fail when
      there is no socio-economic safety net.

PMID- 14708396
TI  - Traditional birth attendants in developing countries cannot be expected to carry
      out HIV/AIDS prevention and treatment activities.
AB  - Pregnancy and birth, fertility and fertility regulation are all greatly affected
      by the exigencies of HIV and AIDS, and vice versa. Women and infants can only
      benefit if the respective policymakers, researchers and service providers in
      sexual and reproductive health and HIV/AIDS, particularly those involved in
      prevention of mother-to-child transmission of HIV, gain greater knowledge of each
      others' expertise and seek to integrate the best of both into the care they each
      offer. The growth in access to antiretroviral treatment for mothers as well as
      infants, including during pregnancy and the breastfeeding period, makes such
      efforts even more timely and crucial. Yet there are worrying signs that
      specialists in both camps are making inappropriate policy and service delivery
      recommendations based on too little knowledge of each others' patches. As an
      example of this problem, this article discusses and rejects a recommendation in a
      recent BMJ article that traditional birth attendants could be trained to carry
      out HIV prevention and possibly provide HIV tests and drugs for prevention of HIV
      transmission during home deliveries in developing countries.

PMID- 14708397
TI  - "Typhoid Mary" and "HIV Jane": responsibility, agency and disease prevention.
AB  - The construction of disease risks as knowable, calculable and preventable in
      dominant social science and public health discourses has fostered a certain kind
      of logic about individual risk and the responsibility for infection. Disease
      control measures that have developed out of this logic typically fail to
      recognise the socio-structural roots of many high-risk behaviours that are linked
      to the spread of infection. Instead, they hold the disease carrier responsible
      for managing his/her own risk of infection of others, and rely on constraining
      the agency of the carrier (e.g. by constraining movement, contact or occupation).
      In occupations associated with a high risk of infection, the idea of
      responsibility of the actor implicitly raises issues of "professional
      responsibility". Using the case of "Typhoid Mary" and a hypothetical case of "HIV
      Jane", this paper explores some of the problems with making sex workers
      responsible for the prevention of HIV transmission. It argues that for the notion
      of "responsibility" to make any sense, the HIV-positive person must be in a
      position to exercise responsibility, and for this they must have agency.

PMID- 14708399
TI  - Sexually transmitted infection control with sex workers: regular screening and
      presumptive treatment augment efforts to reduce risk and vulnerability.
AB  - Sex workers have high rates of sexually transmitted infections (STIs), many of
      them easily curable with antibiotics. STIs as co-factors and frequent unprotected
      exposure put sex workers at high risk of acquiring HIV and transmitting STIs and
      HIV to clients and other partners. Eliminating STIs reduces the efficiency of HIV
      transmission in the highest-risk commercial sex contacts--those where condoms are
      not used. This paper reviews two STI treatment strategies that have proven
      effective with female sex workers and their clients. 1) Clinical services with
      regular screening have reported increases in condom use and reductions in STI and
      HIV prevalence. Such services include a strong peer education and empowerment
      component, emphasize consistent condom use, provide effective treatment for both
      symptomatic and asymptomatic STIs, and begin to address larger social, economic
      and human rights issues that increase vulnerability and risk. 2) Presumptive
      treatment of sex workers, a form of epidemiologic treatment, can be an effective
      short-term measure to rapidly reduce STI rates. Once prevalence rates are brought
      down, however, other longer-term strategies are required. Effective preventive
      and curative STI services for sex workers are key to the control of sexually
      transmitted infections, including HIV, and are highly synergistic with other HIV
      prevention efforts.

PMID- 14708398
TI  - The contribution of sexual and reproductive health services to the fight against
      HIV/AIDS: a review.
AB  - Approximately 80% of HIV cases are transmitted sexually and a further 10%
      perinatally or during breastfeeding. Hence, the health sector has looked to
      sexual and reproductive health programmes for leadership and guidance in
      providing information and counselling to prevent these forms of transmission, and
      more recently to undertake some aspects of treatment. This paper reviews and
      assesses the contributions made to date by sexual and reproductive health
      services to HIV/AIDS prevention and treatment, mainly by services for family
      planning, sexually transmitted infections and antenatal and delivery care. It
      also describes other sexual and reproductive health problems experienced by HIV
      positive women, such as the need for abortion services, infertility services and
      cervical cancer screening and treatment. This paper shows that sexual and
      reproductive health programmes can make an important contribution to HIV
      prevention and treatment, and that STI control is important both for sexual and
      reproductive health and HIV/AIDS control. It concludes that more integrated
      programmes of sexual and reproductive health care and STI/HIV/AIDS control should
      be developed which jointly offer certain services, expand outreach to new
      population groups, and create well-functioning referral links to optimize the
      outreach and impact of what are to date essentially vertical programmes.

PMID- 14708400
TI  - The right to love: the desire for parenthood among men living with HIV.
AB  - Drug regimens and procedures now exist that will prevent parents from
      transmitting HIV to infants, and the ethical and legal obligation to promote and
      protect the reproductive rights of those living with HIV should form part of
      training for HIV/AIDS care and prevention. This paper reports a study that
      investigated issues of sexuality and reproduction with 250 Brazilian men living
      with HIV in Sao Paulo. We asked whether they wished to have children and whether
      health professionals in HIV/AIDS treatment clinics that they attended were
      supportive of their wishes. Health professionals were not considered by most
      participants to be supportive enough or even impartial about HIV-positive people
      having children, and paid little attention to men's fathering role. 80% of the
      men had sexual relationships, and 43% of them wanted children, especially those
      who had no children, in spite of expectations of disapproval. Few of the men
      received information about treatment options that would protect infants, however.
      In previous studies with HIV-positive women attending the same clinics, by
      comparison, greater knowledge about prevention of perinatal HIV transmission was
      reported, but women had fewer sexual relationships, fewer desired to have
      children, and they expected even more disapproval of having children from health
      professionals. We conclude that the rights of those with HIV to found a family
      depend as much on curing the ills of prejudice and discrimination, including
      among health professionals, as on medical interventions.

PMID- 14708401
TI  - Rape and HIV post-exposure prophylaxis: addressing the dual epidemics in South
      Africa.
AB  - In South Africa, a country notable for both a rapidly escalating AIDS epidemic
      and high levels of sexual violence, the issue of HIV post-exposure prophylaxis
      (PEP) following rape has recently come to the fore, and a policy supporting
      provision of PEP has been approved by the national government. This paper
      compares the conditions for providing PEP in Europe and North America with the
      conditions faced by two initiatives in South Africa, one serving a primarily
      rural base, and one urban. It is based on a review of the literature on sexual
      violence in South Africa and use of PEP following occupational and non
      occupational exposure. It incorporates perspectives from in-depth interviews in
      2000 with 18 key informants, including survivors of sexual violence, gender and
      HIV activists, domestic violence NGOs, rape crisis centres, physicians, lawyers,
      researchers and HIV/AIDS advisors in the Department of Health. The paper argues
      that given the scientific evidence for PEP, and the nature of the dual epidemics
      of HIV and sexual violence in South Africa, the public health and social justice
      rationale for implementing PEP equals and indeed exceeds that put forward in
      industrialised countries. However, delays in accessing PEP caused by the public
      justice system and lack of training for service providers constitute significant
      obstacles to effective implementation. In this respect, provision of PEP presents
      an opportunity to reform and strengthen existing services for post-rape care and
      to link attention to the epidemic of sexual violence to HIV/AIDS prevention.

PMID- 14708402
TI  - Between personal wishes and medical "prescription": mode of delivery and post
      partum sterilisation among women with HIV in Brazil.
AB  - HIV-positive women are confronted during pregnancy with a range of medical
      information and prescriptions that substantially affect the experience of
      pregnancy and birth. Based on antenatal and post-partum interviews with 60 HIV
      positive pregnant women from Sao Paulo and Porto Alegre, Brazil, this article
      presents evidence of some of the factors that affect mode of delivery and access
      to post-partum sterilisation, and the implications of these. Whether women gave
      birth vaginally or by caesarean section was medically prescribed, with women's
      own preferences taking second place. Some were advised that caesarean section was
      the only option with HIV in pregnancy; others were told it should be used only
      for medical indications, even if the woman wanted to be sterilised at the same
      time. The women in Porto Alegre were less likely to get a sterilisation than
      those in Sao Paulo, even with caesarean section, as sterilisation was not
      encouraged locally. Many of the women who accepted a caesarean had been convinced
      before they gave birth that it was the best choice for them, either because it
      reduced the risk of perinatal HIV transmission or because it facilitated tubal
      ligation, or both. However, after they gave birth, the women judged their
      experience of delivery and the post-partum period mainly in comparison to
      previous deliveries, and many of them viewed the birth experience with HIV as
      more difficult than previous deliveries and worse than they had expected.

PMID- 14708403
TI  - Pregnant or positive: adolescent childbearing and HIV risk in KwaZulu Natal,
      South Africa.
AB  - In communities where early age of childbearing is common and HIV prevalence is
      high, adolescents may place themselves at risk of HIV because positive or
      ambivalent attitudes towards pregnancy reduce their motivation to abstain from
      sex, have sex less often or use condoms. In this study, we analyse cross
      sectional survey data from KwaZulu Natal, South Africa, to explore whether an
      association exists between the desire for pregnancy and perceptions of HIV risk
      among 1,426 adolescents in 110 local communities. Our findings suggest that some
      adolescents, girls more than boys, were more concerned about a pregnancy if they
      lived in environments where youth were perceived to be at high risk of HIV
      infection. The probability that pregnancy was considered a problem by boys was
      positively correlated with the proportion of adult community members who thought
      youth were at risk of acquiring HIV, and for girls by the proportion of peers in
      the community who thought youth were at risk of HIV. We also found that becoming
      pregnant would be a bigger problem for the African girls than the white and
      Indian girls. The analysis suggests that for some adolescents, in addition to
      effects on educational and employment opportunities, the danger of HIV infection
      is becoming part of the calculus of the desirability of a pregnancy.

PMID- 14708404
TI  - Preventing sexually transmitted infections and unintended pregnancy, and
      safeguarding fertility: triple protection needs of young women.
AB  - The problems and risks of unprotected sex, unintended pregnancy and sexually
      transmitted infections are inextricably linked. In this context, the critical yet
      overlooked problem of infertility also needs to be addressed. Dual protection
      means concurrent protection against unintended pregnancy and STI/HIV. This paper
      argues for a more comprehensive notion of "triple protection" to include the
      safeguarding of fertility. This is intended explicitly to draw out the connection
      between infertility and STIs--using the "visibility" of fertility and infertility
      and people's immediate connection with them--and in so doing to bolster STI
      prevention and control efforts. It could also serve to highlight the connections
      between infertility and unsafe abortion and delivery practices, which still exist
      in many developing countries. Understanding differences in perception and
      weighting of protection concerns by young women and men, whether they wish to
      start, postpone or avoid pregnancy, is essential for the creation of effective
      programmes. Building on efforts to promote dual protection, a strategic
      opportunity exists to include prevention of infertility into safer sex messages
      and to address the fragmentation of reproductive health and HIV/AIDS programmes.

PMID- 14708405
TI  - Vulnerability to HIV/STIs among rural women from migrant communities in Nepal: a
      health and human rights framework.
AB  - Human rights norms and standards can be applied to health issues as an analytical
      tool and as a framework to identify and shape interventions to reduce the impact
      of ill-health and improve the lives of individuals and populations. This article
      discusses how migration, health status, gender-based discrimination and access to
      education have an impact on HIV/STI vulnerability among rural women from migrant
      communities in Nepal. It is based on data from a clinic-based HIV/STI prevalence
      study with 900 women aged 15-49 from two rural communities in Kailali district,
      Western Nepal, and existing legal and policy data. Existing efforts to address
      HIV/STI vulnerability and risk in this population focus primarily on risk-taking
      behaviour and risk-generating situations, and largely fail to address contextual
      issues that create and facilitate risky behaviour and situations. Respecting,
      protecting and fulfilling the rights of individuals can reduce vulnerability to
      HIV/STI infection. Greater emphasis must be given to addressing the gender
      discrimination embedded in Nepalese culture, the acute lack of access to health
      care and education in rural areas, and the precarious economic, legal and social
      circumstances facing many migrants and their families.

PMID- 14708407
TI  - Safer sex and reproductive choice: findings from "positive women: voices and
      choices" in Zimbabwe.
AB  - Positive Women: Voices and Choices was an advocacy-research project developed by
      the International Community of Women Living with HIV/AIDS to explore the impact
      of HIV/AIDS on women's sexual and reproductive lives, challenge the violation of
      their rights and advocate improvements in policy and services. The project in
      Zimbabwe, the first one in three countries, was carried out from 1998 to 2001.
      This article presents selected findings from the Zimbabwe research report. It
      shows that HIV-positive women were unaware they were at risk before an HIV
      diagnosis, and that gender norms and economic dependence on husbands/partners
      restricted women's ability to control their sexual and reproductive lives.
      Prejudices that HIV-positive women should not be sexually active or have children
      meant women did not disclose their status to health workers, making it difficult
      for their needs to be acknowledged or addressed. Condom use was considered
      inappropriate in marriage. Younger childless women wanted to become pregnant,
      often in spite of previous miscarriage and stillbirths. Women with several
      children wanted to avoid further pregnancies, and contraceptive and condom use
      increased markedly after HIV diagnosis, especially among those attending support
      groups. Safe abortion was almost entirely inaccessible, though technically the
      law would have permitted it. Better economic opportunities for women, and
      integrated pregnancy and delivery care, family planning, STI and HIV-related
      services are needed which take account of HIV-positive women's needs.

PMID- 14708406
TI  - Safe abortion for HIV-positive women with unwanted pregnancy: a reproductive
      right.
AB  - About 2.5 million women who become pregnant each year worldwide are HIV-positive.
      UNAIDS recommends that HIV-positive women should be able to control their
      fertility and to prevent HIV transmission perinatally if they decide to have
      children. Yet a literature review on these matters found that termination of
      pregnancy for HIV-positive women receives very little attention. This paper
      describes the difficulties faced by HIV-positive women in obtaining safe, legal,
      affordable abortion services. It shows that voluntary HIV counselling and testing
      for women seeking induced abortions and post-abortion care may not be provided.
      HIV-positive women want to avoid pregnancy for the same reasons as other women,
      but they also do not want to infect their partners through unprotected sex, worry
      about effects of pregnancy and childbirth on their own health, or about infecting
      a child and the child's future care. Little research has been done on whether HIV
      positive women have a greater risk of morbidity following unsafe abortions than
      HIV-negative women, but evidence suggests they might. Studies in Zimbabwe and
      Thailand show that when information and access to legal pregnancy termination are
      lacking, HIV-positive women may be prevented from terminating a pregnancy. The
      paper concludes that it is essential for women living with HIV/AIDS to be able to
      exercise their right to decide whether and when to have children.

PMID- 14708408
TI  - Measurement of condom use as a risk factor for HIV infection.
AB  - Correct and consistent condom use can prevent susceptible people from acquiring
      HIV infection. However, in many countries repeated cross-sectional studies reveal
      a trend of increasing prevalence of HIV infection alongside an increase in
      reported condom use. Changes in sexual behaviour that reduce the number of new
      HIV infections will not become apparent through changes in HIV prevalence until
      some time after the behaviour change takes place. Limitations in the data used to
      assess condom use may also explain the concurrent increases in condom use and HIV
      prevalence. One common indicator of condom use, the UNGASS indicator (condom use
      at last higher risk sex of those aged 15-24), has been chosen to illustrate how
      changes in the proportion of people who report using condoms do not always
      explain changes in the size of the group who had high risk behaviour. Indicators
      based on the proportion of the whole population who have sex without using a
      condom would be better measures of the size of the group at highest risk of HIV
      infection.

PMID- 14708409
TI  - Re-use of the female condom: now for the practical realities.

PMID- 14708410
TI  - Comparison of H2-receptor antagonist- and proton-pump inhibitor-based triple
      regimens for the eradication of Helicobacter pylori in Chinese patients with
      gastritis or peptic ulcer.
AB  - This study compared the efficacy of an H2-receptor antagonist (H2RA)- and a
      proton-pump inhibitor (PPI)-based triple regimen for the eradication of
      Helicobacter pylori infection. Chinese patients with H. pylori-associated
      gastritis or peptic ulcer were randomized to receive the H2RA-based triple
      regimen (20 mg famotidine, 1.0 g amoxicillin and 0.4 g metronidazole) or the PPI
      based triple regimen (20 mg omeprazole, 1.0 g amoxicillin and 0.4 g
      metronidazole) both twice daily for 1 or 2 weeks. Successful eradication of H.
      pylori was determined by the 13C-urea breath test and gastric mucosa histology at
      least 4 weeks after completion of antibiotic therapy. Eradication rates were
      56.0% and 76.9% for the 1-week H2RA- and PPI-based triple regimens, respectively,
      and 81.6% and 82.1% for the 2-week regimens, respectively. The H. pylori
      eradication rate for the 2-week H2RA regimen was significantly higher than that
      for the 1-week regimen, but there were no significant differences between the 1-
      and 2-week PPI regimens. The two regimens proved equally effective in eradicating
      H. pylori infection.

PMID- 14708411
TI  - Congestive heart failure induced by the combination of atrial fibrillation and
      tricuspid regurgitation.
AB  - Atrial fibrillation (AF) and tricuspid regurgitation (TR) may induce congestive
      heart failure (CHD). Using electrocardiography and echocardiography, we examined
      the clinical characteristics and haemodynamic findings in 100 patients with AF +
      TR + CHF, AF + TR, AF or TR. The fractional shortening in all groups with AF was
      significantly decreased compared with the TR group. The ejection fraction in
      patients with AF + TR + CHF was significantly lower than in the TR group. Twenty
      four of the 72 patients with AF and TR (with or without CHF) were treated, and 13
      were monitored for heart rate and severity of TR. Eight months after start of
      treatment the heart rate and typical symptoms and signs of heart failure had
      improved significantly in nine patients, but the severity of TR did not change.
      TR worsened in the remaining four patients but they did not develop CHF. Our
      results suggest that increased heart rate due to the combination of AF and TR
      could be responsible for CHF.

PMID- 14708412
TI  - Comparison of prophylactic anti-emetic effects of ondansetron and dexamethasone
      in women undergoing day-case gynaecological laparoscopic surgery.
AB  - We aimed to determine the effect of ondansetron and dexamethasone on preventing
      post-operative nausea and vomiting (PONV). Sixty women undergoing laparoscopic
      gynaecological surgery were randomized to receive ondansetron 4 mg, dexamethasone
      8 mg or saline. Drugs were administered 2 min before induction of anaesthesia,
      and anaesthesia and post-operative analgesic regimens were standardized. The
      incidence of PONV in the first 24 h after the operation was 35% in the
      ondansetron group, 55% in dexamethasone group and 85% in the control group. A
      significant difference between the groups was only seen in the first 3 h post
      operatively. In this period, ondansetron was significantly more effective than
      dexamethasone and saline, but no differences were seen between dexamethasone and
      saline. In all treatment groups, post-operative visual analogue scale scores,
      sedation scores and usage of analgesics were similar. In conclusion, ondansetron,
      but not dexamethasone, prevented PONV in the first 3 h after gynaecological
      laparoscopic surgery.

PMID- 14708413
TI  - Comparative efficacy of oral and intravenous calcitriol treatment in
      haemodialysis patients: effects on serum biochemistry and cytokine levels.
AB  - This study compared the effects of oral and intravenous calcitriol on serum
      biochemistry parameters and levels of bone-resorptive cytokines in haemodialysis
      patients. Patients were randomized to receive oral (n = 18) or intravenous (n =
      16) calcitriol treatment for 6 months. Serum levels of total calcium, ionized
      calcium, intact parathyroid hormone (iPTH), magnesium, alkaline phosphatase,
      tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 were
      measured at baseline and after 3 and 6 months of treatment. After treatment,
      serum levels of iPTH, total calcium, ionized calcium, TNF-alpha, IL-1 and IL-6
      were not significantly different from baseline. The intravenous calcitriol
      treatment group showed significant decreases in levels of iPTH, TNF-alpha, IL-1
      and IL-6 and a significant increase in total calcium level after 3 and 6 months.
      There was no significant change in serum ionized calcium levels. Significantly
      decreased serum alkaline phosphatase and magnesium levels were found in both
      treatment groups after 3 and 6 months. In conclusion, intravenous calcitriol
      treatment has a significant depressive effect on iPTH and bone-resorptive
      cytokines in patients undergoing haemodialysis.

PMID- 14708414
TI  - The effect of caudal bupivacaine versus tramadol in post-operative analgesia for
      paediatric patients.
AB  - In this study 20 paediatric surgical patients were randomized to two groups after
      induction of general anaesthesia. Group 1 received 0.25% bupivacaine (2 mg/kg)
      and group 2 received 5% tramadol (2 mg/kg) both as a caudal block. Heart rate,
      mean arterial pressure, arterial oxygen saturation, respiratory rate and pain and
      sedation scores were recorded at 1, 2, 4, 6, 12 and 24 h post-operatively.
      Acetaminophen was administered rectally (20 mg/kg) if the pain score was > 3/10.
      The pain and sedation scores in group 2 were significantly lower compared with
      group 1. There were no significant differences in heart rate, mean arterial
      pressure, arterial oxygen saturation and respiratory rate between the two groups.
      In conclusion, caudal tramadol was superior to bupivacaine in analgesic efficacy
      and in reducing the need for additional analgesia during the post-operative
      period in paediatric patients.

PMID- 14708415
TI  - Upregulation of cardiac ghrelin mRNA in leptin-deficient and leptin receptor
      deficient mice with viral myocarditis.
AB  - Expression of cardiac and gastric ghrelin messenger (m) RNA, together with heart
      and body weights, were measured in leptin-deficient (ob) and leptin receptor
      deficient (db) mice with heart failure induced by viral myocarditis. Significant
      elevations in cardiac ghrelin mRNA levels and heart weight were observed in ob
      and db mice 10 days after viral inoculation compared with baseline values.
      Expression of gastric ghrelin mRNA was not upregulated in ob and db mice on day
      10. The elevated expression of cardiac ghrelin mRNA seems to compensate for the
      lack of upregulation in gastric ghrelin mRNA.

PMID- 14708416
TI  - Adhesion preventive effect of a novel hyaluronic acid gel film in rats.
AB  - This study evaluated the efficacy of a novel hyaluronic acid (HA) gel for
      preventing adhesions in a rat caecal model. The gel was manufactured from an
      acidic HA solution using a freezing procedure. HA gel films with four different
      half-lives (50-200 h) in physiological buffered saline at 37 degrees C were
      prepared, by regulating the freezing time, and tested. The HA gel film was
      applied as a barrier on the injured caecal surface after standardized treatment
      with a rotary abrasion apparatus. A control group of 20 animals were abraded in
      the same way but not treated. Seven days after the initial operation, the
      incidence and severity of any adhesions were recorded. Application of the HA gel
      film significantly reduced the incidence and severity of adhesion formation in
      all treatment groups compared with the control group. This novel HA gel film is
      effective for reducing post-operative adhesions in this rat model and the
      resorption rate is optimum for adhesion prevention on the caecal surface.

PMID- 14708417
TI  - DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right
      ventricular hypertrophy in a rat model of pulmonary hypertension.
AB  - This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor,
      on the compensatory development of right ventricular hypertrophy in monocrotaline
      (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT
      were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg
      or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated
      increased right ventricular weight, pulmonary artery medial wall thickening,
      myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP)
      concentration and reduced body weight gains. DA-8159, however, markedly
      attenuated the compensatory development of right ventricular hypertrophy and
      pulmonary artery medial wall thickening, amplified the increase in plasma cGMP
      levels and increased lung cGMP concentrations. In addition, DA-8159 prevented
      myocardial fibrosis induced by MCT. These results demonstrate that DA-8159
      attenuates the compensatory development of right ventricular hypertrophy in a
      rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH,
      but its efficacy in humans needs evaluating.

PMID- 14708418
TI  - Kidney damage by dietary Fusarium graminearum in rats: a microscopic study.
AB  - Fusarium graminearum is a fungus frequently isolated from cereal grants. In this
      study, the histopathological effects of dietary F. graminearum on rat kidneys
      were examined. Treated rats and controls were fed F. graminearum-inoculated and
      non-inoculated rice, respectively. After 14 days, all the rats were killed and
      their kidneys were removed and examined using light microscopy. The kidneys of
      the rats in the treatment group were characterized by the following
      histopathological findings: patch-like mononuclear cell infiltrations in the
      cortex; prominent necrosis of proximal tubules; debris areas containing
      mononuclear cells and degraded renal tubules; shrunken and densely eosinophilic
      apoptotic cells in the proximal tubule epithelium; karyorrhexis and mitotic
      figures in the epithelium of both proximal and distal tubules; and many apoptotic
      bodies in the areas between the renal tubules. It was concluded that dietary F.
      graminearum caused inflammation and tubular damage in the rat kidney. This is the
      first microscopic study showing that F. graminearum ingestion is associated with
      renal damage.

PMID- 14708419
TI  - A new approach to drug therapy in non-alcoholic steatohepatitis (NASH).
AB  - Liver steatosis is a common human disease, most often caused by long-term alcohol
      consumption. Non-alcoholic steatohepatitis (NASH) is characterized by similar
      histopathological features to those observed in alcoholic liver disease, but
      occurs in the absence of significant alcohol consumption. Several aetiological
      factors contribute to NASH: obesity, type 2 diabetes mellitus, hyperlipidaemia,
      pregnancy, different chemical intoxications, parenteral nutrition, jejeuno-ileal
      bypass, chronic inflammatory bowel disease, nutritional protein deficiency and
      congenital metabolic disorders. Biochemically, oxidative stress and lipid
      peroxidation and their ensuing damage are implicated in the pathogenesis of NASH
      and alcoholic steatohepatitis (probably resulting from free fatty acids in the
      mitochondria, and induction of the cytochrome P450 isoform CYP2E1 in hepatocytes
      and Kupffer's cells). This paper deals with the pathomechanisms, clinical
      findings and currently available therapies for NASH. The potential use of
      metadoxine in the treatment of NASH is also discussed.

PMID- 14708420
TI  - Acupressure versus oxybutinin in the treatment of enuresis.
AB  - We aimed to assess the efficacy of acupressure for treating nocturnal enuresis,
      compared with oxybutinin. Acupressure was administered to 12 patients by their
      parents, who had been taught the technique. Pressure was applied at acupuncture
      points Gv4, Gv15, Gv20, B23, B28, B32, H7, H9, St36, Sp4, Sp6, Sp12, Ren2, Ren3,
      Ren6, K3 and K5. Twelve control patients received 0.4 mg/kg oxybutinin. Parents
      were asked to record incidences of bed-wetting and patients and/or parents
      completed a questionnaire 15 days and 1, 3 and 6 months after the start of
      treatment. Complete and partial responses after 6 months of treatment were seen
      in 83.3% and 16.7%, respectively, of patients treated with acupressure, and in
      58.3% and 33.3%, respectively, of children who received oxybutinin. In
      conclusion, nocturnal enuresis can be partially treated by oxybutinin but
      acupressure could be an alternative non-drug therapy. Acupressure has the
      advantages of being non-invasive, painless and cost-effective.

PMID- 14708421
TI  - Anatomical characteristics of the tibial medullary canal and their implications
      for intramedullary fixation.
AB  - The use of intramedullary fixation methods in the tibia is limited by the
      anatomical characteristics of this bone. In this study, the shape and degree of
      axial lateral rotation of the medullary canal were determined in 45 human dry
      cadaver bones using X-ray and computed tomography examinations and direct
      measurement of rotation in inserted nails. Forty bones (88.8%) had slight and
      five bones (11.1%) had excessive anterior bowing along the tibial shaft. Six of
      the 45 bones (13.3%) had an extremely narrow medullary canal. Axial lateral
      rotation was demonstrated in the middle third of the medullary canal, being on
      average (+/- SD) 32.35 +/- 16.25 degrees (range 10-75 degrees). This study
      revealed that extreme narrowing of the medullary canal, axial lateral rotation of
      the medullary canal, and extreme anterior bowing of the tibial shaft are the
      anatomical characteristics most likely to cause difficulties when using
      intermedullary fixation in the tibia.

PMID- 14708422
TI  - An open-label study investigating the efficacy and safety of 12-96 weeks of
      telmisartan treatment in patients with hypertension.
AB  - This open-label, multicentre, multinational trial evaluated the efficacy and
      safety of telmisartan used alone or as add-on therapy in 2121 adults with mild-to
      moderate essential hypertension. Patients received telmisartan 40-80 mg once
      daily for 12 weeks and could participate in the study for up to 96 weeks, or
      until a marketed supply of telmisartan became available. Mean change from
      baseline in mean seated trough diastolic blood pressure (DBP) after 12 weeks'
      treatment, the primary endpoint, was -11.8 mmHg in the intent-to-treat
      population. The corresponding mean change in mean seated trough systolic blood
      pressure (SBP) was -20.2 mmHg. Both changes were statistically significant. Mean
      DBP and SBP reductions were apparent from week 4 and maintained throughout the
      treatment period. Telmisartan was well tolerated; the most common adverse events
      were headache (6%) and dizziness (3%), and 10% of adverse events were considered
      drug-related. In conclusion, telmisartan is an effective and well-tolerated drug
      when used as monotherapy or add-on treatment in this broad population of
      patients.

PMID- 14708423
TI  - Suppression of alveolar bone resorption by etidronate treatment for periodontal
      disease: 4- to 5-year follow-up of four patients.
AB  - Four women with periodontitis received intermittent cyclical etidronate
      (etidronate administered orally at a dose of 200 mg/day for 2 weeks, at intervals
      of 10-12 weeks or 6 months) for 4-5 years in addition to ordinary dental therapy.
      Alveolar bone density was measured using a new method comparing the percentage
      increase in density. Mean alveolar bone density increased significantly during
      intermittent cyclical etidronate treatment. Significant reductions were observed
      in the mobility of the teeth and the depth of periodontal pockets. There were
      significant correlations between alveolar bone density and both mobility of the
      teeth and the depth of the alveolar pockets. It is concluded that increases in
      alveolar bone density are associated with the clinical benefits of etidronate in
      the treatment of periodontitis.

PMID- 14708424
TI  - Wellens' syndrome: a case report.
AB  - The pattern of clinical findings and electrocardiography (ECG) changes known as
      Wellens' syndrome is associated with significant stenosis of the proximal left
      anterior descending coronary artery. Cases can be classified according to the ECG
      pattern into type 1 (biphasic T waves) or type 2 (deeply inverted T waves,
      especially in leads V2 and V3). We present here an unusual case of Wellens'
      syndrome in which the ECG pattern changed from type 2 to type 1 during
      observation, and in which the coronary lesion was in the middle rather than the
      proximal part of the left anterior descending artery.

PMID- 14708425
TI  - Grounded theory in nursing research: Part 1--Methodology.
AB  - The epistemological underpinnings of grounded theory make it valuable in the
      study of nursing, which is premised on an interpersonal process between nurses
      and clients. Further, it is a useful style of research when there is little prior
      information about a topic. In this article (Part 1), Terence McCann and Eileen
      Clark outline the key features of this methodology. In the follow-up article
      (Part 2, McCann and Clark 2003a), a critique is provided of grounded theory and
      the two main approaches to this methodology. In the final article in the series
      (Part 3, McCann and Clark 2003b), the authors illustrate how grounded theory can
      be applied to nursing research with examples from McCann's Australian study
      (McCann and Baker 2001) of how community mental health nurses promote wellness
      with clients who are experiencing an early episode of psychotic illness.

PMID- 14708426
TI  - Grounded theory in nursing research: Part 2--Critique.
AB  - In the first article in this series (McCann and Clark 2003), the methodological
      characteristics of grounded theory were examined. In this, the second article on
      grounded theory, Terence McCann and Eileen Clark critique the methodology. They
      then summarise the main differences between Glaser's approach and Strauss and
      Corbin's approach to grounded theory.

PMID- 14708427
TI  - Grounded theory in nursing research: Part 3--Application.
AB  - In the first article in this series, the methodological characteristics of
      grounded theory were examined (McCann and Clark 2003a). In the second article, a
      critique was presented of the methodology, with particular reference to the
      approaches of Glaser, and Strauss and Corbin (McCann and Clark 2003b). In this,
      the final article in the series, Terence McCann and Eileen Clark illustrate how
      to apply the methodology to nursing research using the example of McCann's
      Australian study (McCann and Baker 2001) of how community mental health nurses
      promote wellness with clients who are experiencing an early episode of psychotic
      illness.

PMID- 14708428
TI  - The use of grounded theory to study interaction.
AB  - In this paper Hanna Maijala, Eija Paavilainen and Paivi Astedt-Kurki examine the
      use of grounded theory from the perspective of data analysis. The paper reports
      on the findings of a Finnish study of interaction between caregivers and families
      expecting an impaired child. The objective of the study was to describe and
      explain the social processes between caregivers and families expecting an
      impaired child by identifying the central descriptive concepts, their
      interconnections, and the overall structure of the interaction process. The
      authors conclude that grounded theory is a diverse approach to studying
      interaction, and that the constant comparative method is a challenge to a
      researcher's perseverance and flexibility.

PMID- 14708429
TI  - The 'invisible' nursing RAE 2001--an analysis.
AB  - In the United Kingdom the Research Assessment Exercise (RAE) is a major method of
      assessing research from Higher Education institutions. Participation is not
      compulsory, and anecdotal evidence suggests that many eligible institutions did
      not enter the Unit of Assessment for nursing (UoA 10). In this paper, Bruce
      Lindsay, Michael Pfeil and Kaen Bates describe a study designed to establish the
      approach to the 2001 RAE taken by institutions that were eligible to enter the
      nursing unit but had not done so. This included an assessment of their rationales
      for not entering UoA 10, and an analysis of the grades awarded to tose that
      entered nursing research in other UoAs. The study identified a small group of
      researchers whose work informs a range of health and social care disciplines.
      Their non-submission to UoA 10 may have resulted from a lack of clarity about
      criteria for this Unit: future RAEs could improve the standard of UoA 10 by
      producing clearer guidelines for submissions.

PMID- 14708430
TI  - Developing self-evaluation skills: a pragmatic research-based approach for
      complex areas of nursing.
AB  - Using a newly established community rehabilitation service as the research
      context, Gill Hek explores ways in which practitioners pragmatically developed
      self-evaluation research skills. Within the practice setting, community
      practitioners learnt how to conduct and analyse interviews with service users,
      and to develop connected database records that could be used across health and
      social services. The teaching-learning process and the teacher-learner
      relationship were used as models for researching in this complex area. The
      project demonstrated how community rehabilitation teams developed self-evaluation
      research skills to a point where they were able to reflect critically on the
      service they were providing. Supported by a research team, they were able to use
      research skills to analyse the volume and throughput of their service. They were
      also able to establish what needed to be done next within the challenging
      environment at the interface of health and social care in the community.

PMID- 14708431
TI  - RCN research developments.

PMID- 14708432
TI  - [Infectious diseases: extending the traditional views].

PMID- 14708434
TI  - [Role of the antioxidative defense system in the pathogenesis of acute viral
      hepatitides].
AB  - AIM: To study the activity of antioxidative defense enzymes and the total plasma
      antioxidative activity in patients with viral hepatitis B, C, and mixed hepatitis
      B + C. MATERIALS AND METHODS: 77 patients with viral hepatitis B, 90 with viral
      hepatitis C, and 25 with mixed hepatitis B + C were followed up. The activity of
      superoxide dismutase and catalase of leukocytes, and the total plasma
      antioxidative activity were determined at the peak of the disease, alleviation of
      clinical symptoms, and before discharge from hospital. RESULTS: At the peak of
      the disease, the patients with viral hepatitides showed suppressed activities of
      superoxide dismutase and catalase of leukocytes and suppressed total plasma
      antioxidative activity with increased these parameters by early convalescence,
      but without their normalization. There were the most pronounced changes in
      patients with severe mixed hepatitis B + C. CONCLUSION: The changes found in the
      body's antioxidative defense have been ascertained to depend on the etiology,
      stage, and severity of viral hepatitis.

PMID- 14708433
TI  - [Autoimmune manifestations in acute viral hepatitides].
AB  - AIM: To study autoimmune reactions in patients with acute viral hepatitis A, B,
      and C in the dynamics of an infectious process. MATERIALS AND METHODS: 134
      patients with acute viral hepatitides of various etiology were examined. Among
      them there were 36 patients with acute viral hepatitis A, 40 with B, and 58 with
      viral hepatitis C. Antinuclear antibodies (ANA), antismooth muscle antibodies
      (SMA), and antimitochondrial antibodies (AMA) were determined by
      immunofluoresence assay using the test systems ATS COMVI-1, IMMCO diagnostics
      (USA). Serum rheumatoid factor was detected by the semiquantitative latex
      agglutination test on a slide manufactured by the "Human" firm (Germany).
      Cryoglobulins were identified by the qualitative visual method. RESULTS: SMA, ANA
      were detected in the diagnostically significant titers (1:40-1:160) in patients
      with acute viral hepatitis A, B, and C. A distinction of autoimmune
      manifestations was ascertained in viral hepatitis C. It has been demonstrated
      that in 71% of the patients cryoglobulins appear in the acute period of the
      disease and, in their presence, rheumatoid factor was found in 17.2% and 6.9%
      exhibited anti-LKM-1 and AMA. CONCLUSION: The presented data on the nature and
      time course of changes in autoimmune reactions in patients with acute viral
      hepatitis A, B, and C during an infectious process suggest that autoimmune
      disorders are characteristic of viral hepatic lesions just at the early stages of
      the disease irrespective of its etiology and play a prominent role in the
      pathogenesis of these nosological entities.

PMID- 14708435
TI  - [Clinical and laboratory features of severe forms of acute viral hepatitis B].
AB  - AIM: To establish the clinical and laboratory features of severe forms of acute
      viral hepatitis B (AVHB). MATERIALS AND METHODS: 141 patients (88 males and 53
      females) with different forms of the disease were examined. Among them there were
      30, 33, and 78 patients with mild, moderate, and severe AVHB, respectively. In 23
      patients, the course of hepatitis was complicated by acute hepatic failure; 6 of
      them developed hepatic coma that resulted in death. All the patients underwent
      comprehensive clinical and biochemical studies; some of them did a special
      laboratory study including immunological monitoring, determination of some
      parameters of lipid peroxidation (LPO) and the antioxidative system (AOS) in the
      blood cells, examination of blood rheological properties (by the deformability
      and viscosity of erythrocytic biomembranes), and determination of the level of
      endogenous toxemia by the content of medium molecular-weight peptides in the
      plasma, red blood cells, and urine. RESULTS: Pathogenetic features of severe
      forms of AVHB have been identified. These include: 1) a hyperimmune response to
      the invasion of mixed cellular and humoral virus, followed by hepatic
      macrophageal hyperactivation; 2) high activity of LPO with the development of AOS
      failure; 3) deterioration of erythrocytic rheological properties: the decreased
      deformability and increased viscosity of their biomembranes; 4) the maximal level
      of endogenous toxemia. CONCLUSION: New agents to enhance the efficiency of
      treatment of patients with severe AVHB should be sought in the following
      directions: immunomodulating, antioxidative, membrane-stabilizing, and
      disintoxicant ones.

PMID- 14708436
TI  - [HG-viral infection in adults].
AB  - AIM: To characterize the clinical and laboratory manifestations in patients with
      HG viral infection frequently concurrent with chronic HCV infection and the
      potentialities of their treatment. MATERIALS AND METHODS: 109 patients with
      suspected chronic hepatic disease were examined. The markers of HGV, HCV, HBV,
      and TTV infections were determined. The possible factors of infection,
      biochemical parameters, and the efficiency of antiviral therapy were assessed.
      RESULTS: Hepatitis G virus RNK was detected in 32 cases, a combined variant of
      hepatitis G + C viruses RNA was found in 77 patients with chronic viral hepatitis
      (CVH). Among the presumed routes of contamination in the mixed variant of CVH,
      there were most common intravenous injection of narcotic drugs; in monoinfection
      (HGV), there were parenteral interventions in medical facilities and blood
      transfusion. Antiviral treatment of 13 patients with chronic HGV + HCV infection
      yielded a positive result in 5 patients after 3-month therapy. CONCLUSION: In
      patients with CVH, HG virus infection was more frequently observed in combination
      with CVHC, less frequently as monoinfection. In HG virus monoinfection,
      biochemical studies revealed the enhanced activity of transaminases and
      hyperbilirubinemia that was absent in the mixed variant of HGV + HCV. The
      financial capacities of patients should be taken into account while choosing
      therapy.

PMID- 14708437
TI  - ["Hematological masks" of chronic viral hepatitis].
AB  - AIM: To reveal the structural features of the red blood cell membrane in patients
      with prolonged persistence of hepatitis B virus (HBV) and hepatitis C virus
      (HCV). MATERIALS AND METHODS: 61 patients with moderate and mild chronic viral
      hepatitis B and C were examined. A control group comprised 22 healthy donors.
      Fluorescence of the red blood cell membrane was performed, by using the following
      probes: pyrene, phenylnaphthylamine, 1-anilinonaphthalene-8-sulfonate. The
      activity of the ion-transporting enzyme Na+, K(+)-ATPase was determined. RESULTS:
      Increases in the microviscosity of the lipid bilayer, periprotein lipid
      environment, as well as the structural modification of the surface layers of the
      membrane were found in patients with chronic hepatitis B and C. The activity of
      the membrane-bound enzyme Na+, K(+)-ATPase was statistically significantly
      decreased as compared with that in healthy donors. CONCLUSION: In HBV and HCV
      infection, the impairments of the red blood system are highly diversified: they
      involve bone marrow compartment of an erythron, as earlier shown, and its
      peripheral one. Molecular disorganization of the red blood cell membrane fails to
      present with obvious red blood cell dysfunctions. Despite the multifactorial
      property of their occurrence, impairments of the red blood system are mediated
      and corrected by many regulatory mechanisms at different organizational levels
      and may be compensated.

PMID- 14708438
TI  - [Characteristics of cellular immunity in children with acute viral hepatitis A].
AB  - AIM: To study the populational composition of lymphocytes and the specific
      features of production of cytokines in children with acute viral hepatitis A
      (AVHA). MATERIALS AND METHODS: 128 patients aged 11 to 14 years who had AVHA,
      moderate AVHA being in 83.5% were examined. In 87.2% of the children, the disease
      was cyclic. The etiology of the disease was verified by simultaneously detecting
      anti-HAV IgM (enzyme immunoassay) and by the presence of HAV RNA (polymerase
      chain reaction) in the blood. Peripheral lymphocytes (CD) were phenotypes in the
      indirect immunofluorescence test using monoclonal antibodies; cytokines were
      determined by the enzyme immunoassay; serum beta 2-microglobulin was done by
      radioimmunoassay. RESULTS: The children with AVHA were found to have elevated
      levels of tumor necrosis beta-factor, interleukin-1 beta (IL-1 beta), and IL-4 in
      the icteric period, as well as a decrease in their levels at convalescence. IL-6
      was detected in individual patients only in the first 3 days of the icteric
      period. The peak of AVHA was characterized by relative lymphocytosis, by
      decreases in the counts of T helper/inductor cells and natural killer cells, by
      increases in the count of CD25 cells, convalescence, by preserved lymphocytosis,
      by the increased levels of T lymphocytes that carry the markers CD3, CD4, CD8,
      CD16, CD25, and CD95, and by higher toxicity of beta 2-microglobulin.

PMID- 14708439
TI  - [Development of approaches to enhancing of patient adherence to antivirus therapy
      in the treatment of human immunodeficiency virus infection].
AB  - AIM: To study approaches to enhancing adherence of HIV-infected patients
      receiving antiretrovirus therapy. MATERIALS AND METHODS: 25 patients (including 3
      females) aged 18 to 45 years receiving VAART (fortovasa + norvir + videx, and
      viramun) were examined. While treating the patients, group classes were conducted
      to enhance their adherence to the therapy, followed by individual consultations
      in order to consolidate the obtained effect. The adherence to the therapy was
      rated by the patients' self-reports. RESULTS: There was an increase in the
      activity and openness of those who attended group classes and positive changes in
      their self-assessment. Approaches to enhancing adherence and a model of school
      for HIV-infected individuals were developed. CONCLUSION: It has been shown that a
      combination of patients' awareness of different HIV-infection-associated problems
      with consulting allows treatment motivation to be increased.

PMID- 14708440
TI  - [Magnetic resonance relaxometry of serum in patients with different forms of
      cellulitis in the dynamics of the disease].
AB  - AIM: To study the time of nuclear magnetic resonance (NMR) of spin-lattice serum
      relaxation (T1) in the dynamics of an infectious process in patients with
      different forms of erysipelas. MATERIALS AND METHODS: 37 patients with different
      clinical forms of erysipelas were examined in the acute period of the disease and
      in the early period of convalescence. RESULTS: A statistically significant
      increase in T1 NMR was ascertained in patients with bullous hemorrhagic
      erysipelas as compared with those with erythematous form. CONCLUSION: Pronounced
      changes in the functional status of serum in patients with hemorrhagic forms of
      erysipelas are of great importance in the development of the local hemorrhagic
      syndrome.

PMID- 14708441
TI  - [Use of affinity interaction of biologically active substances in practice of
      public health system].
AB  - AIM: To determine the potentialities of use of affinity interaction of
      immobilized biologically active substances (bacterial cells or their fragments,
      toxins, antigens of various chemical nature, immunoglobulins, enzymes,
      gangliosides, etc.) for medical practice. MATERIALS AND METHODS: Emulsion
      polymerization of acrylamide monomers in the gaseous nitrogen current was used as
      a basic method for preparation of solid-phase magnetic immunosorbents (MIC). A
      procedure for preparation of siliceous MIC was also applied. The prepared MICs
      were used a solid phase in enzyme immunoassay and immunofluorescence assay and
      the recorded data were compared with those of studied conventionally used in
      practical medicine. RESULTS: The use of MIC made it possible to detect pathogens
      of particularly dangerous infections in large volumes of the samples contaminated
      with another microflora. With the proposed MIC, one can stand a good chance of
      surveying large contingents of the population, of obtaining the quantitative
      results in shorter periods to establish a diagnosis. With this, the sensitivity
      and specificity of immunoassays substantially increase. Whether MIC may be used
      as selective hemosorbents to remove specific antibodies from the blood of
      patients with rheumatic diseases for therapeutic purposes was studied.
      CONCLUSION: The findings are indicative of wide potentialities of use of affinity
      interaction of biologically active substances immobilized on inert carriers with
      the inserted magnetic material in the laboratory diagnosis of diseases of both
      infectious and autoimmune nature, which may be widely used in the in- and
      outpatient settings.

PMID- 14708442
TI  - [WHO MONICA program-based study of awareness of their health and health attitude
      in males and females aged 25-64 years from Novosibirsk].
AB  - AIM: To assess the attitude of the Novosibirsk population towards its health, its
      readiness to participate in preventive measures and to implement guidelines for
      changing lifestyle. MATERIALS AND METHODS: A random representative sample of
      males and females (a total of 2400 individuals) aged 24 to 64 years from one of
      the Novosibirsk districts was examined within the framework of the second
      screening of the MONICA program studying the trends and monitoring cardiovascular
      diseases and the "MOPSY-MONICA-psychosocial" subprogram. The examination included
      the conventional procedures described in the MONICA project. Sleep disorders,
      health self-assessment, and attitude to smoking were studied by means of the
      questionnaire "Awareness and Attitude towards Health" adapted to the studied
      population. RESULTS: More than 60% of the males and 85% of the females reported
      that they were not quite healthy or ill, only 7% of the individuals had their
      health examined although almost 100% noted that they were most likely to fall ill
      with a serious disease within 5-10 years. The males were more optimistic in their
      assessments than were the females. With age, the frequency of assessments, such
      as "not quite healthy" and "ill", concern about their health, and participation
      in prophylactic examinations increased. 45% of the respondents reported about the
      high level of stress in their working place. The opportunity of the examinees to
      have a rest at home was extremely little. Family stress was significant for both
      sexes. The females showed a more negative attitude towards smoking than did the
      males (55% of the males and 5% of the females were smokers). The males more
      frequently considered that they did not need to alter dietary habits and to do
      exercises than did the females. A total of 2.4% of the males and 2.5% of the
      females changed their dietary habits for their health. Only 50% of the males and
      31% of the females slept well or very well, this parameter decreased with age.
      CONCLUSION: Despite a positive motivation in the context of prophylaxis, there
      are negative trends in both social and behavioral characteristics of the
      population. The most intensive measures for altering the behavioral
      characteristics of the population and for softening the impact of stress on the
      population are required at the governmental level.

PMID- 14708443
TI  - [Comparative evaluation of cardiac hemodynamics and endothelium-dependent
      reactive hyperemia in people with arterial hypertension living in high-altitude
      and plain areas].
AB  - AIM: To reveal the specific features of cardiac hemodynamics and endothelial
      function in high-altitude native dwellers with arterial hypertension (AH).
      MATERIALS AND METHODS: 90 native dwellers from high-altitude and plain areas, who
      had Stages I and II AH, were examined. To assess cardiac contractility, central
      and peripheral hemodynamics, the authors used electrocardiography,
      echocardiography, tetrapolar impedance rheoplethysmography. The functional status
      of the endothelium was evaluated by the reproduction of endothelium-dependent
      reactive hyperthermia in the antebrachial vessels. RESULTS: The patients with
      Stages I and II AH who live in high-altitude area have been found to have less
      pronounced peripheral vasocontriction due to the less suppression of pump and
      contractile functions of the heart. Total peripheral resistance in high-altitude
      dwellers with Stage II AH is practically similar to that in plain inhabitants
      with Stage I AH. The extended vasodilator reserve in high-altitude inhabitants
      with AH is also shown by the data obtained in the reproduction of reactive
      hyperemia in the antebrachial vessels. A less marked decrease in this vascular
      reaction in patients with AH who live in high-altitude areas may be due to
      additional production and/or release of nitric oxide in order to increase the
      vasodilator reserve in moderate hypoxia. CONCLUSION: The course of AH in high
      altitude dwellers is marked by less suppression of cardiac pump and contractile
      functions and less peripheral vasoconstriction. This may be accounted for by
      compensatory activation of endothelial vasodilator mechanisms aimed at preserving
      adequate tissue perfusion and at optimally providing the body with oxygen in
      moderate hypoxia.

PMID- 14708444
TI  - [Effect of long-term antihypertensive therapy on vaso-regulating function of the
      brachial artery in patients with arterial hypertension associated with type 2
      diabetes mellitus].
AB  - AIM: To evaluate the impact of 6-month-to-one-year antihypertensive therapy on
      the vasoregulating junction of the brachial artery and predictors of its
      efficiency in 75 patients with stages I-II arterial hypertension associated with
      type 2 diabetes mellitus. MATERIALS AND METHODS: An open randomized study of
      parallel groups of patients receiving angiotensin-converting enzyme (ACE)
      inhibitors, calcium blockers (verapamil) and their combination and in those who
      did not take antihypertensive therapy examined endothelium-dependent vasodilation
      (EDVD) according to the data of ultrasound scanning and Doppler study of brachial
      arterial blood flow as compared with changes in metabolism and 24-hour blood
      pressure profile. RESULTS: A positive effect of verapamil on the baseline
      impaired EDVD is realized only in the presence of an adequate compensation of
      glycemia, at the normal blood level of cortisol, occurs in parallel with
      increased nonendothelium-dependent vasoreactivity, and associates with the
      magnitude of an antihypertensive effect. ACE inhibitors improve decreased EDVD
      irrespective of the degree of glycemic control, the blood level of cortisol
      without a clear correlation with the altered non-endothelium-dependent
      vasoreactivity and with the degree of an antihypertensive effect. Combined
      therapy with these agents causes decreases in baseline insulinemia and the
      athoregenicity index and it can improve impaired vasoreactivity even in case of
      incomplete antihypertensive therapeutic effect. CONCLUSION: The differences found
      in the effect of ACE inhibitors and verapamil on baseline decreased EDVD provide
      evidence for differential use of these drugs to correct impaired vasoreactivity
      in patients with AH associated with DM. The combined antihypertensive therapy
      fails to produce a positive impact if significant hypercholesterolemia (total
      blood cholesterol being more than 6.5 mmol/l) and stenosing peripheral
      atherosclerosis are present.

PMID- 14708445
TI  - [Content of the antigenic determinants CD16, CD25, CD95, and HLA-DR in induced
      sputum of patients with bronchial asthma and chronic obstructive bronchitis].
AB  - AIM: To examine the content of CD16, CD25, CD95, and HLA-DR antigenic
      determinants in induced sputum (IS) of patients with bronchial asthma (BA) and
      chronic obstructive bronchitis (COB). MATERIALS AND METHODS: The study enrolled
      36 patients with BA and 15 with COB whose age was 21 to 58 years. The cellular
      precipitate of IS served as a material for the study. The studied receptors were
      determined by immunofluorescence using the "Clonospectrum" monoclonal antibodies.
      RESULTS: There was an increase in the content of CD16, CD25, HLA-DR, CD95 whose
      expression was decreased when glucocorticosteroids were used. At remission of
      asthma, the level of these receptors approximated that in the control group. On
      an exacerbation of COB, the content of these markers was significantly less than
      that in the controls and the use of antibacterial agents and methylxanthines led
      to its rise. At remission of COB, CD16 and CD25 cells were not recorded.
      CONCLUSION: The levels of membrane markers in IM of patients with BA and COB
      depend on the period of the disease and used therapy.

PMID- 14708446
TI  - [Evaluation of the efficacy of inhaled glucocorticosteroids in mild bronchial
      asthma].
AB  - AIM: To develop a procedure for evaluating the efficacy of antiinflammatory
      agents in mild persistent bronchial asthma. MATERIALS AND METHODS: 76 patients
      with mild bronchial asthma were given long acting theophylline. If a complete
      clinical and functional effect was absent, the inhaled glucocorticosteroid
      budesonide was added to the therapy. Before and after therapy, the forced
      expiratory volume per second and forced vital capacity (FVC) were measured many
      times within 24 hours, by using two procedures: 1) that involving morning and
      diurnal tests using short acting beta 2-agonists and 2) that without a
      bronchodilator. The time of onset of the plateau of values of different
      functional indices obtained during monitoring and their dispersion in the stable
      state were automatically calculated. The reliability of indices for evaluating
      the efficiency of antiinflammatory therapy was compared. RESULTS: There were
      great differences in the patients' response to therapy: a complete clinical and
      functional effect of therapy with long acting theophylline alone (n = 9) and in
      combination with budesonide (n = 56). Moreover, therapy-resistant patients (n =
      11) were identified. When a complete therapeutic effect was achieved, the
      clinical symptoms of the disease disappeared before the onset of the plateau of
      values of the most reliable functional indices. A comparative analysis of the
      indices has indicated that the ratio of the morning value of FVC measured just
      after awakening to its best personal value throughout the study was most
      convenient for the patients and reliable. CONCLUSION: The authors propose to use
      the index "ratio of the morning value of FVC measured just after awakening to its
      best personal value the percentage", by calculating the dispersion of this index,
      which characterizes the steady state of the expiratory respiratory system in
      order to evaluate the efficiency of antiinflammatory therapy for bronchial asthma
      and to solve other problems that require functional monitoring.

PMID- 14708447
TI  - [Hypogammaglobulinemic sprue].

PMID- 14708449
TI  - [Hormonal and immunological aspects of renal lesions in patients with chronic
      alcoholism].
AB  - AIM: To analyze a relationship of the level of sex hormones to the tension of
      immunological processes in definite renal diseases in patients with chronic
      alcoholism. MATERIALS AND METHODS: 43 patients with chronic alcoholism who also
      suffered from chronic renal disease were examined. The levels of plasma
      testosterone and estradiol were determined by radioimmunoassay using labeled 3H
      hormones, as described by V. S. Goncharov and G. V. Katsiya. The immunity was
      assessed by determining the activity of secreted interleukin-1 in the cultured
      peripheral monocytes of the patients and in the cultured renal glomerular
      mesangial cells by radioimmunoassay according to the procedure of S. Mizel and O.
      V. Gabrilevskaya. The obtained renal biopsy specimens were examined by electron
      microscopy immunoassay, as described by A. A. Ivanov. The activity of lysosomal
      enzymes was studied. RESULTS: Activation of lysosomal enzymes and increased
      synthesis of interleukin-1 by monocytes and mesangial cells were observed in
      patients with chronic alcoholism and renal diseases with testosterone deficiency
      and excess estradiol in the plasma. There was a correlation of the level of
      estradiol with that of interleukin-1 and with the activity of cathepsin D.
      CONCLUSION: With hypofunction of androgens, estrogens stipulate the tension of
      immune reactions, which finally leads to renal lesion in patients with chronic
      alcoholism.

PMID- 14708448
TI  - [Results of an open multicenter study of the efficiency of one-week anti
      helicobacter therapy using omeprazole, clarithromycin, and amoxicillin in
      patients with duodenal peptic ulcer].
AB  - AIM: To study the efficiency of one-week antihelicobacter therapy using
      omeprazole, clarithromycin, and amoxycillin in patients with duodenal peptic
      ulcer during its recurrence. MATERIALS AND METHODS: 105 patients with recurrent
      peptic ulcer and a not less than 0.5-cm ulcer in the duodenal bulb was given
      triple therapy: omeprazole, 20 mg twice daily, amoxycillin, 1000 mg twice daily,
      and clarithromycin, 500 mg twice daily for 7 days. Then the patients were allowed
      to take antacids if they were required to abolish the symptoms of recurrent
      peptic ulcer. H. pylori was detected in the mucosal biopsy specimens taken from
      the anthral part and body of the stomach at gastroduodenascopy, by using the
      rapid urease test and histology. Gastroduodenoscopy was performed before and 4-6
      weeks after the triple therapy. RESULTS: The major symptoms of recurrent peptic
      ulcer were eliminated in 90% of the patients by the end of a course of therapy,
      i.e. on its day 7. By the control time, the rate of ulcer cicatrization was
      99.05% (104/105). The coincidence of results of the two tests has indicated that
      H. pylori eradication was 81.9% (86/105) 4-6 weeks after termination of
      treatment. Adverse reactions during therapy were observed in 20% of the patients;
      however, treatment had to be discontinued only in 2.9% of the patients.
      CONCLUSION: One-week triple therapy using omeprazole, clarithromycin, and
      amoxycillin in highly effective in treating duodenal peptic ulcer during its
      recurrence.

PMID- 14708450
TI  - [Diagnosis and treatment of intestinal candidiasis].

PMID- 14708451
TI  - [Herpesvirus esophagitis].

PMID- 14708452
TI  - [Current aspects of sepsis pathogenesis].

PMID- 14708453
TI  - [Myocardial infarction in elderly patients. Role of beta-adrenoblockers in the
      treatment and secondary prevention].

PMID- 14708454
TI  - Evaluation of the antioxidant activity of new carotenoid-like compounds by
      electron paramagnetic resonance.
AB  - The antioxidant activity of a novel series of derivatives with a carotenoid-like
      structure was studied. These derivatives have recently been isolated chemically
      as a result of studies on the pigments present in a particular species of birds,
      namely parrots. These novel derivatives, which are also called parrodienes, have
      been proved to possess interesting biological properties that differ from those
      that carotenoids are known to have. The objective of this study was to
      demonstrate the ability of these novel compounds to inhibit the formation of
      reactive oxygen species, especially their ability to block the formation of
      hydroxyl radicals, which are among the most reactive products of oxygen reactions
      and which produce the greatest damage to cells and tissues. The technique used to
      assess this antioxidant capacity of parrodienes was electron paramagnetic
      resonance, which allows direct assessment of inhibition of hydroxyl radical
      formation (.OH). The results show that these derivatives, especially octatriene,
      are able to exert evident antioxidant activity, thus confirming that their
      antioxidant properties are important for their biological activity.

PMID- 14708455
TI  - Comparison of chloroxylenol 0.5% plus salicylic acid 2% cream and benzoyl
      peroxide 5% gel in the treatment of acne vulgaris: a randomized double-blind
      study.
AB  - A 12-week double-blind randomized study was performed to compare benzoyl peroxide
      5% (BP) gel and chloroxylenol 0.5% plus salicylic acid 2% (PCMX + SA) cream
      (Nisal cream) for efficacy and adverse reactions. Thirty-seven volunteers
      participated in the study, 19 in the BP group and 18 in the PCMX + SA group. The
      patients applied the medication twice daily to the entire face. Clinical
      evaluation and lesion counts were obtained at 0, 3, 6, 9 and 12 weeks. At week 12
      both groups showed a marked improvement in both inflammatory and noninflammatory
      lesions (60% and 54% for the BP group and 62% and 56% for and 56% for the PCMX +
      SA group, respectively). Although PCMX + SA showed a slightly stronger
      keratolytic effect throughout the study period, there was no statistically
      significant difference in the reduction of the papulopustules or comedones
      between the two groups. Adverse effects such as erythema and photosensitivity
      were significantly fewer in the PCMX + SA group at week 12 (p = 0.0002 and p =
      0.05, respectively). These results suggest that PCMX + SA cream is as effective
      as BP gel in the treatment of papulopustular and comedonal acne and that it is
      better tolerated.

PMID- 14708456
TI  - Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition,
      antihistaminic and antispasmodic activities of Aller-7, a novel botanical
      formulation for allergic rhinitis.
AB  - Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a
      major challenge to health professionals. A large number of the world's
      population, including approximately 40 million Americans, suffers from allergic
      rhinitis. A novel, botanical formulation (Aller-7) has been developed for the
      treatment of allergic rhinitis using a combination of extracts from seven
      medicinal plants, including Phyllanthus emblica, Terminalia chebula, T.
      bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum,
      which have a proven history of efficacy and health benefits. The clinical
      manifestations of allergy are due to a number of mediators that are released from
      mast cells. The effect of Aller-7 on rat mesenteric mast cell degranulation was
      studied by incubating different concentrations of Aller-7 and challenging them
      with a degranulating agent, compound 48/80. The inhibitory activity of Aller-7
      was determined against lipoxygenase and hyaluronidase, the key enzymes involved
      in the initiation and maintenance of inflammatory responses. Furthermore, most of
      these manifestations are due to histamine, which causes vasodilatation,
      increasing capillary permeability and leading to bronchoconstriction. Hence, the
      antihistaminic activity of Aller-7 was determined is isolated guinea pig ileum
      substrate using cetirizine as a positive control. The antispasmodic effect of
      Aller-7 on contractions of guinea pig tracheal chain was determined using
      papaverine and cetirizine as controls. Aller-7 exhibited potent activity in all
      these in vitro models tested, thus demonstrating the novel anti-allergic
      potential of Aller-7.

PMID- 14708458
TI  - Pilot study of S-1 in patients with disseminated gastric cancer.
AB  - The prognosis for patients with advanced gastric cancer remains poor. Peritoneal
      metastasis is the most frequent cause of death in patients with gastric cancer,
      but the most appropriate treatment for patients with disseminated gastric cancer
      remains uncertain. S-1 is a newly developed oral fluoropyrimidine derivative with
      unusually high activity against several tumor types. The aim of this study was to
      evaluate the feasibility and efficacy of S-1 for the treatment of patients with
      disseminated gastric cancer. A total of 31 patients with primary or recurrent
      gastric cancer with peritoneal dissemination were entered into this study. One
      course of this single-drug therapy consisted of S-1 (80-120 mg) twice daily for
      28 days, followed by a 2-week period of no treatment. These treatments were
      repeated until disease progression or patient refusal. With a median follow-up
      period in survivors of 293 days, the median survival time was 357 days.
      Toxicities were mild and no patient withdrew from treatment before disease
      progression. Grade 3 hematotoxicity was observed in only one patient. S-1 showed
      promising activity against gastric cancer with peritoneal dissemination and
      acceptable toxicity. Further evaluation of S-1 treatment is warranted in this
      disease.

PMID- 14708457
TI  - Comparative effect of clinidipine and quinapril on left ventricular mass in mild
      essential hypertension.
AB  - The aim of this study was to compare the regressive effect of clinidipine on left
      ventricular mass (LVM) with that of quinapril. Sixty patients with mild essential
      hypertension aged more than 39 years were randomly allocated to two groups to
      receive cilnidipine (10 mg; n = 30) or quinapril (10 mg; n = 30). The patients
      underwent echocardiography before and 12 months after drug treatment. Sixteen
      patients in each group underwent 123I-metaiodobenzylguanidine (MIBG) cardiac
      imaging before and 12 months after drug treatment. In both groups systolic and
      diastolic blood pressures significantly decreased to similar levels. In the
      clinidipine group, both end-diastolic and end-systolic diameters and posterior
      wall thickness significantly decreased, while only end-systolic diameter
      significantly decreased in the quinapril group. However, LVM (206 +/- 36 g to 189
      +/- 40 g, p < 0.02 for the quinapril group, 195 +/- 60 g to 171 +/- 48 g, p <
      0.004 for the clinidipine group) and the LVM index (127 +/- 20 g/m2, to 116 +/-
      20 g/m2, p < 0.02 for the quinapril group, 121 +/- 32 g/m2 to 106 +/- 24 g/m2 p <
      0.003 for the clinidipine group) significantly decreased in both groups.
      Regarding MIBG imaging, in the cilnidipine group, the heart-to-mediastinum ratio
      significantly increased (p < 0.02) and the washout rate significantly decreased
      (p < 0.02) after drug treatment. In contrast, there were no significant changes
      in MIBG parameters in the quinapril group. Clinidipine produced a greater
      decrease in LVM in essential hypertension than quinapril, probably due to the
      long-term suppression of the cardiac sympathetic nervous system. Clinidipine is
      useful for hypertensive patients with left ventricular hypertrophy and may
      improve their prognosis.

PMID- 14708459
TI  - Pharmacological suppression of rat distal colon chloride secretion requires two
      blockers.
AB  - Rat distal colon epithelium is frequently employed to assess the effect of
      natural and synthetic chemicals on chloride secretion. Inhibition of chloride
      secretion is often reported as the loop diuretic-sensitive portion of short
      circuit current (Isc). The present work challenges the hypothesis that a loop
      diuretic alone is able to fully abolish chloride secretion. Isolated mucosa
      preparations were mounted in an Ussing chamber. The effects on short-circuit
      current of replacement of normal Ringer by a low (2.5 mmol/L) Cl solution and of
      blockers of basolateral Na, K, 2 Cl symport (bumetanide), apical Cl channels
      (diphenylamine-2-carboxylate, DPC), and anion exchange (4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid, SITS) alone and combined were
      assessed. Low Cl reversibly decreased Isc by 76%. In normal Ringer, bumetanide
      decreased Isc by 65%. SITS also had a significant effect at the serosal side, but
      not at the apical side, where DPC caused a 40% decrease. Chloride replacement,
      bumetanide and DPC, but not SITS, increased epithelial resistivity. Combined
      blockade of Na, K, 2 Cl symport and apical Cl channels, of Na, K, 2 Cl symport
      and anion antiport, or of anion antiport and apical Cl channels was needed to
      achieve reduction of short circuit current to the same extent seen with chloride
      replacement. Present results indicate that Isc of the unstimulated epithelium is
      mostly due to chloride secretion, and at least two blockers are required to
      abolish it. This fact should be taken into account in studies of chloride
      secretion-stimulating agents.

PMID- 14708460
TI  - Gastric emptying rates in idiopathic dyspepsia with and without "hunger pain".
AB  - It has been previously observed that in dyspeptic patients with "hunger pain",
      that is, with pain suggestive of the presence of peptic ulcer, only 12% had an
      endoscopically demonstrated ulcer, the remaining 88% showing absence of important
      macroscopically detectable lesions (idiopathic dyspepsia). In order to
      investigate the possibility of a relationship between "hunger pain" and some
      alteration in gastroduodenal motility, the gastric emptying rates of patients
      presenting idiopathic dyspepsia with and without "hunger pain" were compared with
      those of normal control subjects. The study was conducted in 40 patients
      presenting idiopathic dyspepsia, 20 with and 20 without "hunger pain", and 30
      voluntary apparently normal control subjects. The patients and the controls
      ingested, with a standard breakfast, a gelatine capsule containing 10 radioopaque
      polyurethane markers, and the gastric emptying of the markers was evaluated
      taking 3 x-ray films of the abdomen at 1.5, 3.0 and 4.5 hours after the
      breakfast. The gastric emptying rates of the markers were significantly higher in
      the patients with "hunger pain", and significantly lower in the patients without
      "hunger pain", than in the normal control subjects. In idiopathic dyspepsia with
      and without "hunger pain" there are, respectively, abnormally increased and
      abnormally decreased gastric emptying rates of undigestible solid markers. Our
      findings could help to better understand the pathogenesis of those different
      types of dyspepsia and, consequently, to improve their treatment.

PMID- 14708461
TI  - [Complications of endoscopic retrograde cholangiopancreatography].
AB  - INTRODUCTION: Endoscopic sphincterotomy (ES) is commonly used to remove bile-duct
      stones and to treat other problems. We prospectively investigated complications
      and mortality of endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS
      AND METHODS: Between june 6, 1998 and june 6, 1999 553 ERCP were performed in our
      centers. Inclusion criteria for protocol were: ERCP indication, complete follow
      up and informed consent. We prospectively studied complications of ECRP in
      consecutive patients treated at 2 institutions (San Martin Hospital, La Plata,
      Argentina and Hadassah University Hospital, Jerusalem, Israel). The follow-up was
      done during 365 days with a clinical examination, laboratory test and
      ultrasonography to determine the possible complications. RESULTS: Of 553 ERCP, 43
      had a complications; including pancreatitis in 16 cases, cholangitis in 12,
      hemorrhage in 5, perforation in 3 and miscellaneous in 7. 3-1) ES frequency: 241
      patients (pts). 3-2) FOLLOW-UP: 365 days in 504 pts. 3-3) Sex and age: women 274
      pts, men 230 pts. Age range 1 month to 90 year old. 3-4) Final diagnoses:
      choledocholitiasis (38.8%), strictures (18%), pancreatic cancer (4.3%), ampullary
      cancer (2.3%) and normal ERCP (24.4%). CONCLUSIONS: The rate of complications
      after ES can vary in different circumstances and is primarily related to the
      indication for the procedure and to endoscopic technique. Our percentage of
      complications (7.53%) coincide with consulted studies. Today, diagnostic ERCP has
      been challenged by magnetic resonance cholangiography (MRC). MRC provides images
      of the billary and pancreatic ducts that are nearly equal to those of ERCP
      without the procedural risk associated.

PMID- 14708462
TI  - [Helicobacter pylori seroprevalence in dialysis patients].
AB  - AIM: (a) to establish Hp infection seroprevalence among patients under chronic
      dialysis and to compare it with that of general population, (b) to assess the
      relationship between Hp prevalence and parameters associated with a higher
      morbidity, such as serum albumin levels, dialysis adequacy, and quality of life
      in this population. METHODS: Ninety-three consecutive patients of both genders
      (58 M/35 F), X 57.5 +/- 17.2 years old, with end-stage chronic renal failure on
      maintenance dialysis were included. All of them received dialysis at Hospital
      Italiano, Buenos Aires. The presence of anti-Hp antibodies was established and
      its prevalence was compared with a control group. In all cases, serum albumin
      levels and time in dialysis were determined. In addition, dialysis adequacy was
      established by KT/V and quality of life was measured with Karnofsky's index.
      Patients and controls were matched according variables associated with Hp
      infection in our country, i.e., age, socioeconomic and education levels. RESULTS:
      Ninety-three dialysis patients were matched with 93 controls. According to the
      quick serological test, 44 out of 93 (47.3%) dialyzed patients and 55 out of 93
      (53.6%) controls were Hp positive (ns). Forty-one out of 76 patients (53.9%) with
      a serum albumin level 3.5 g/dl and 3/17 (17.6%) with a serum albumin level < 3.5
      g/dl were anti-Hp positive (odds ratio, 0.06; 95% CI, 0.01-0.39; p < 0.01). Fifty
      five out of 80 patients (69.2%) with Kt/V > 1.2 and 6/13 (43.8%) with Kt/V 1.2
      Pounds were anti-Hp positive (odds ratio, 0.10; 95% CI, 0.02-0.65; p < 0.05).
      Four out of 15 patients (26.7%) with Karnofsky's index > 70, and 40/78 (51.3%)
      with Karnofsky's index < or = 70 were anti-Hp positive (odds ratio, 0.37; 95% CI,
      0.06-2.95, p = 0.26). CONCLUSION: According to our results, dialysis patients do
      no represent a high-risk group of Hp infection. Those individuals with higher
      morbidity and mortality rates as evidenced by low serum albumin levels or by a
      low Kt/V have a lower Hp prevalence, perhaps due to a poor immune response o due
      to the use of antibiotics. Therefore, Hp infection screening en dialysis units
      does not differ from the guidelines developed in Maastrich for the general
      population.

PMID- 14708463
TI  - [Virtual Colonoscopy. Experience in 500 patients].
AB  - OBJECTIVE: To show our experience and results in Virtual Colonoscopy (VC).
      MATERIAL AND METHOD: Five hundred patients with personal or familial history of
      colorectal carcinoma and/or adenomas, or any kind of coloproctologic symptoms
      were studied. VCs were practiced using a helical CT scanner (300 patients) and a
      multislice CT scanner (200 patients) a few hours after Conventional Colonoscopy
      (CC), considered the gold standard. The patients were evaluated in a prospective
      blind study, to determine sensitivity and specificity of VC. Findings were
      classified as: 1) normal studies; 2) studies with pathological findings. This one
      was subdivided into: 2a) Lesions below 5 mm., 2b) Lesions between 5-9 mm., 2c)
      Lesions above 9 mm. RESULTS: VC detected 253 normal studies whereas CC only
      detected 233. The sensitivity and specificity for each subgroup were: 2a) 87.8%
      and 86.9%; 2b) 95.6% and 91.4%; 2c) 100.0% and 100.0% respectively. CONCLUSION:
      VC is a feasible and useful method for evaluating the entire colon. It is well
      tolerated, it has no complications and a high sensitivity and specificity for
      elevated lesions, especially the ones above or equal to 5 mm.

PMID- 14708464
TI  - [Bruner's gland hyperplasia: case report and literature review].
AB  - Bruner's gland hyperplasia (BGH) is an infrequent benign injury located on the
      first or second portion of the duodenum. We presented the case of a 59 year-old
      man with vomits, diarrhea, upper gastrointestinal bleeding intermittent and loss
      of weight in which was a nodule in the duodenum that corresponded to an
      hyperplasia nodular of Brunner's gland.

PMID- 14708465
TI  - [Primary esophageal lymphoma in a patient with AIDS].
AB  - Primary esophageal lymphomas are extremely rare. We report a primary esophageal T
      cell lymphoma of a diffuse large cell phenotype B in a patient with AIDS. Also we
      reviewed other published cases. The diagnosis of this complication should be
      considered in HIV seropositive patients with progressive displagia and endoscopic
      findings of masses, polyps or ulcerations and, specially in those unresponsive to
      antifungal or antiviral therapy. Biopsy and histopathologic studies are needed to
      confirm the diagnosis.

PMID- 14708466
TI  - [Helicobacter pylori in children in Hospital Nacional de Ninos, San Jose de Costa
      Rica].
AB  - Infection with Helicobacter pylori is more prevalent in developing than in
      developed countries. Several publications from Costa Rica associate this agent
      with almost 70% of the adults suffering gastritis; however, there are not data
      about its prevalence in children. In order to address that gap in the
      epidemiology of Helicobacter pylori in Costa Rica, we study 264 children (3
      months to 17 years old) remitted to upper endoscopy due to dyspeptic disorders.
      From each case at least two biopsies were taken; one for Helicobacter isolation
      and the others for histopathological study. 96 of the children showed any grade
      of gastritis and in 73 of them was identified H. pylori; also, this agent was
      associated with 11 of the children without alteration in their gastric mucosa. In
      total, H. pylori was identified in the 31.8% of the studied cases. The two
      younger patients infected were a 1 and 2 years-old boys; the former had normal
      mucosa and the other had gastritis. These data confirm the importance of
      investigate Helicobacter in young children with gastric discomfort, mainly in
      developing countries.

PMID- 14708467
TI  - [Virtual Colonoscopy].

PMID- 14708468
TI  - [Prevalence of hepatic involvement, alcoholism, hepatis B, C and HIV in patients
      with background history of drug use].
AB  - Drug addicts frequently have liver diseases for different reasons: alcohol abuse,
      the drugs themselves, but more often hepatitis B and C infections. AIDS is common
      in this population as well and could also affect the liver directly or in the
      form of hepatocellular or biliary damage. We conducted this study to determine
      the prevalence of liver diseases, alcoholism, hepatitis B and C infections, and
      HIV positivity in this population. We studied a cohort of 137 persons, all with a
      history of drug abuse, and investigated the quantity of alcohol intake, the kind
      of drug used, and he routes of drug administration. RESULTS: We found liver
      disease in 33.6%. The prevalence of alcoholism was 65.4%, of HCV 67.3%, and of
      HBV 17.3%. HDV was undetectable, whereas we found HIV at a frequency of 17.3%.
      HCV RNA was detected in 85.4% of HCV. The drug most often used was cocaine at
      90.4%, followed by marihuana at 88.3%; LSD use occurred in 17.5%. We found
      parenteral drug use in 43.1%. We performed 22 liver biopsies, 21 associated with
      HCV, and detected histological changes consistent with chronic hepatitis in 17,
      with cirrhosis in 4, and with hepatocellularcarcinoma in 1.

PMID- 14708469
TI  - [Mechanism of inhibition OF COX-2 and COX-3 in gastrointestinal damage induced by
      NSAID in rats ].
AB  - In randomized groups of Wistar rats, the effect inhibitor of selective NASAID
      over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2,
      COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The
      conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given
      gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given
      preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given
      massive necrosis preferential in small intestine.

PMID- 14708470
TI  - [Role of chromoendoscopy in colorectal polyps handling].
AB  - INTRODUCTION AND AIM: Endoscopic polipectomy and its further histopathologic
      study are current gold standard in diagnosis of colorectal polyps is. It was
      proposed that colonoscopy with high resolution videoendoscopes with or without
      magnification combined with indigo carmin dye (ICD) could distinguish between
      adenomatous and nonadenomatous polyps according to their pit pattern. The aim of
      this study was to establish sensitivity and specificity of chromoendoscopy with
      ICD using conventional videoendoscopes and fiber-endoscopes with videocamera, to
      make a differential diagnosis of polyp histology and their possible role in colon
      cancer screening. PATIENTS AND METHODS: Step 1: Using previous trial data, the
      first 20 polyps < = 1 cm was retrospectively correlated with their known
      histology to determine the pit pattern of each histologic type; this data was
      used in the step 2 patients. Step 2: 46 patients with colorectal polyps were
      enrolled in this prospective study. Polyps were sprayed with 0.4% ICD, after that
      the polyps were sorted into adenomatous or non, they were all removed and
      submitted for histophatologic evaluation. STATISTICAL ANALYSIS: The chi square
      method was used. RESULTS: 19 patients were evaluated with videoendoscopes (group
      1) and 27 with fiberendoscopes (group 2); in seven cases the pattern of the
      polyps could not be identified and the patients were excluded. Group 1:
      coincidence prediction/histology 94.7% (p < 0.0001), sensitivity 100% and
      especificity 88%. Group 2: coincidence prediction/histology 65.8% (p < 0.05),
      sensitivity 86% and especificity 60%. CONCLUSIONS: Adenomatous and non
      adenomatous polyps can be distinguished by chromoendoscopy with high sensitivity
      and specificity. However, because fiberendoscopy could ot be identify pit pattern
      in 15.2% and has a low negative predictive value we do not recommend to use it.
      Nevertheless, the results obtained with ideo-endoscopes involve potential
      usefulness in colon cancer screening and possible decrease in their risks and
      costs.

PMID- 14708471
TI  - [Utilization of polymerase chain reaction for detection and genotyping of
      Helicobacter pylori in gastric biopsy using paraffin: a retrospective study].
AB  - BACKGROUND: Helicobacter pylori infection is presumed to be the major causal
      agent of chronic active gastritis in humans. The persistent infection with this
      pathogen would be an important factor in the pathogenesis of peptic ulcer and
      also gastric cancer. METHODS: We investigated relationship between H. pylori
      characteristics in 42 patients with normal mucosa or gastritis with minor changes
      and 40 patients with mild and severe gastritis. Detection and typing of vacA and
      cagA genes were performed using a polymerase chain reaction method. RESULTS: The
      analysis of vacA prevalence and the type (S1 or S2) showed non-significant
      differences between the two groups studied (p > 0.05). However, cagA analysis
      showed highly significant differences between the groups classified as normal
      tissue-weak gastritis and mild-severe gastritis (p < 0.0001; OR = 8.4; CI = 3.1
      22.8). CONCLUSIONS: cagA status is associated to the grade of gastritis, finding
      higher frequencies of H. pylori cagA+ in the moderate-severe gastritis group.
      These highly significant differences could make cagA status a genetic marker for
      disease progress.

PMID- 14708473
TI  - [Diaphragmatic traumatic chronic hernia. Report of 3 cases].
AB  - Diaphragmatic traumatic chronic hernias are infrequent. Diagnostic can be
      difficult if don't exist suspicion and treatment is always by surgery. The aim of
      this paper is to present three cases and makes an actualisation in basis to our
      experience and the literature.

PMID- 14708472
TI  - [Acid-supressing capacity of omeprazole 20 mg tablets vs pantoprazole 20 and 40
      mg tablets. A pilot study in volunteers].
AB  - OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg
      tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24
      h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial
      in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0,
      basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash
      out" for 7 days and thereafter 7 more days' therapy with PZ or OZ. On day 22 a 24
      h intragastric pH control was performed again. In the last treatment stage, all
      of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH
      recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in
      which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL
      22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57
      +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001.
      Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4)
      0.65. CONCLUSIONS: According to the results it might be stated that both proton
      pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is
      more effective than pantoprazole as acid-supressor, with statistically
      significative differences. There was no difference between 20 mg omeprazole and
      40 mg pantoprazole.

PMID- 14708475
TI  - [Chromoendoscopy, a little used aid in our environment ].

PMID- 14708474
TI  - [The compromise of esophagus in HIV/AIDS diseases].
AB  - Esophageal disease is a common complication in patients infected with human
      immunodeficiency virus type-1 (HIV-1). Dysphagia, odynophagia and retrosternal
      pain are the most common symptons associated with the esophageal compromise.
      Esophageal candidiasis, the most frequent opportunistic infection, may occur in
      patients with long-standing infection or may be a manifestation of the
      seroconversion. Cytomegalovirus and Herpes simplex virus are more likely to
      produce esophageal ulcers or erosions. HIV itself may be responsible for
      ulcerative esophagitis. Neoplasms as Kaposi's sarcoma, are an infrequent cause of
      symptomatic disease. Barium esophagography and specially upper endoscopy are the
      most commonly employed diagnostic modalities for the evaluation of symptomatic
      patients. Endoscopy may be warranted to make a rapid diagnosis such that specific
      therapy will not be delayed. The use of a combination of histologic, cytologic,
      mycologic and virologic studies is necessary to provide an etiologic diagnosis of
      these lesions.

PMID- 14708476
TI  - [Low contrast weakens illusory contours but enhances the lightness filling-in of
      the Kanizsa square].
AB  - This study systematically investigated the relationship between the lightness
      filling-in of the test field and the clarity of illusory contours. The Munsell
      values of pacmen were N2.5, N3.5, N4.5, N5.5, N6.5 and N7.5, and those of the
      test field were N3.0, N4.0, N5.0, N6.0 and N7.0, respectively. Seventeen subjects
      (age: 20-28 yr.) observed 35 stimuli including five control stimuli. The
      lightness filling-in of the test field increased as the difference in brightness
      between the test field and pacmen decreased. On the contrary, the clarity of
      illusory contours decreased as the difference decreased. These results suggest
      that the lightness filling-in and the clarity of illusory contours have different
      roots.

PMID- 14708477
TI  - [The effect of selective attention to emotional stimuli on recognition memory in
      anxiety].
AB  - It has been argued that the selective attention characteristic of trait anxiety
      does not significantly influence on memory. However, attention to stimuli is
      considered to accelerate memory performance of the stimuli in general. The
      present study examined whether the selective attention due to emotional valences
      could reflect on recognition memory in individuals with high anxiety. In the
      encoding phase, a set of pairs of emotional and neutral words was presented. The
      duration of presentation of stimuli was manipulated in two conditions (1,300 ms
      vs. 2,000 ms). There was no difference in responses for stimuli between with
      positive and with negative valences. In the short-presentation condition,
      compared to the control group, the high-anxious group demonstrated greater
      discrimination for emotional (positive and negative) stimuli relative than for
      neutral ones. Their false alarm rate, on the other hand, was consistently higher
      than the subjects in the low-anxious group. Results in the present study
      suggested that selective attention that the high-anxious subjects allocated to
      emotional stimuli could influence performance of recognition of those stimuli.

PMID- 14708478
TI  - [Culture and the concept of friendships: how do Japanese children resolve a
      conflict between their best friend and a newcomer?].
AB  - This study examined how Japanese children resolve a conflict between their best
      friend and a newly-arrived transfer student; and whether their concepts of
      friendship and promise developed as those of Western children. A total of 125
      children and college students, seven to 24 year old, of both genders were
      individually asked to report their moral understanding of friendship in a semi
      structured interview. A Selman-type friendship dilemma of positing a conflict
      between a newcomer and their best friend was used. As expected, the average
      developmental stages scores, indicating understanding of the meaning of "friend"
      increased with the participant's age, in much the same way as in Western
      children. However, many resolved the conflict through a different strategy from
      those of their Western counterparts. They made an inference regarding the
      newcomer's emotion, seriously took into consideration, and expressed preference
      to solve the problem through the three playing together. The role of social
      representation mediating culture effects on social behavior discussed.

PMID- 14708479
TI  - [Constraint-based approach to individual differences in insight problem-solving].
AB  - In this study, we explored individual differences in insight problem-solving.
      According to the dynamic constraint relaxation theory (Hiraki & Suzuki, 1998),
      there are three sources of individual differences in insight problem-solving: the
      initial strengths of constraints, the evaluation of problem-solving attempts, and
      the learning rate that updates the strength value of each constraint. In order to
      validate the theory's predictions, we compared the subjects who could solve a
      geometric insight problem within 10 minutes with those who could not. A
      microscopic analysis of the solution processes and rating task revealed that the
      initial strengths of the constraints and the adequacy of evaluation are different
      between the two, but their learning rates are not. These results suggest that
      insightful problem-solvers try non-standard attempts more often even in the
      initial phase of their problem-solving and evaluate their attempts more
      precisely. The results were discussed in contrast with other approaches to
      insight.

PMID- 14708480
TI  - [Perceptual judgments of novel contour shapes and hierarchical descriptions of
      geometrical properties].
AB  - Previous studies of pattern psychophysics have suggested that a form property
      such as the number of turns and a structural property such as symmetry were
      useful cues for perceptual judgments of simple forms. However, it is necessary
      for complete descriptions of more complex forms to use hierarchical indices
      reflecting global and local characteristics. In this study, we clarified what
      geometrical properties contributed to complexity and similarity judgments of
      novel shapes, and examined differences between the two judgments, using Fourier
      descriptors as a form property, and symmetropy as a structural property. Global
      and local unevenness were derived from the amplitude of Fourier descriptors, and
      the hierarchical representation was found in both judgment data. Whereas
      complexity judgment was based on local unevenness and global symmetry, similarity
      judgment was, it was suggested, mainly based on global unevenness and symmetry.
      Moreover, it became clear that geometrical properties important for complexity
      data were a subset of those for similarity data. These results suggested that
      more dimensions in geometrical properties were necessary for similarity judgment
      than complexity judgment.

PMID- 14708481
TI  - [Effects of shift work schedule on mood changes among female nurses].
AB  - This study examined the short-term effects of shift work on mood changes. The
      subjects were 1,608 Japanese female nurses, working on rotating 3-shift schedules
      consisted of day, evening, and night shift. Repeated measurements of six
      dimensions of mood and sleep hours in four consecutive days were analyzed.
      Prominent changes of subjective fatigue, activity and confusion were observed
      especially when shift changes occurred (e.g., day shift to night shift or night
      shift to evening shift). The changes of mood were contingent to those of sleep
      hours, which suggested the close association between them. However, the mood
      changes were observed even after adjusting for the effect of sleep hours,
      indicating that irregular sleep pattern is not the only cause that affects mood.

PMID- 14708482
TI  - [An investigation of the unit of activation in on-line inferences during text
      processing: word-unit or proposition-unit?].
AB  - This study investigated the unit of activation in on-line inferences. To explore
      whether the activation of inferences is a word-unit or a proposition-unit, a
      meaningfulness-decision task was devised as a priming measure. The task required
      participants to decide whether a series of short sentences was meaningful or not.
      The result of Experiment 1 suggested that only proposition-units were activated.
      A priming effect was observed in targets which described inferences both at word
      level and proposition-level, but not in targets which described inferences at
      word-level only. In Experiment 2, a meaningfulness-decision task was administered
      to investigate word-based priming and to make sure that the result of Experiment
      1 was not caused by characteristics of the task. In Experiment 3, a priming
      effect was found in targets which described inferences using alternative
      perspectives and words. These results suggest that the unit of activation in on
      line inferences is proposition-units and that these activations relate to the
      proposition-semantic level, not the word or single-concept level.

PMID- 14708483
TI  - [Automatic activation of addition and multiplication facts: an examination of
      effects of SOA, problem size, and presentation of operator symbol].
AB  - The purpose of this study was to examine boundary conditions and time course in
      automatic activation of addition and multiplication facts. Utilizing a number
      matching task in which subjects were required to verify whether a target had been
      presented in a previously viewed number pair, the stimulus onset asynchrony
      (SOA), problem size, and operator symbol were manipulated. As a result, products
      were rejected more slowly than unrelated numbers in all problem size conditions,
      but sums were rejected more slowly than unrelated numbers only in small size
      condition, and this effect was not related to SOA and operator symbol. These
      results suggest that (a) automatic activation is restricted to small facts in
      addition, but not restricted in multiplication, (b) operator symbols have no
      effect on automatic activation, and (c) time course in automatic activation of
      addition facts does not differ from that of multiplication facts.

PMID- 14708484
TI  - [The effect of the use of mobile phone text messages on freshmen's loneliness
      during the transition to college].
AB  - This longitudinal study investigated the extent to which the use of mobile phone
      text messages, including e-mail and short message service, affected freshmen's
      loneliness during the transition to college. A total of 83 freshmen completed
      measures of loneliness and social network at the beginning and end of their first
      semester. Perceived utility of mobile phone text messages was assessed at the
      beginning of the semester. Results showed that perceived functional usefulness
      and affiliation fulfillment of text messages affected formation of social network
      during the period. It was found that the higher the functional usefulness, the
      larger increase in the number of messages to college friends, and the higher the
      affiliation fulfillment, the less important the text messages to pre-college
      friends. Furthermore, it was noted that the more important the relationship with
      pre-college and college friends that was not dependent on text messages, and the
      fewer messages to pre-college friends, the less the loneliness. In contrast,
      greater importance of text messages to pre-college friends was associated with an
      increase in loneliness.

PMID- 14708485
TI  - Control charts: valuable quality tools if you know why, when to use.
AB  - Charts track process variation over time, identifying potential problems. A
      process that is in control is not necessarily a good process. Don't put the cart
      before the horse; first identify the process that needs improvement.

PMID- 14708486
TI  - System launches 3-level plan to cut ED crowding.
AB  - Improved communications and enlisting volunteers are key strategies. Targeted
      survey establishes a baseline of community attitudes. Emergency department
      magazine, videos help support patient education efforts.

PMID- 14708487
TI  - Flexible job options help maintain quality.
AB  - Pensions, other benefits adjusted to accommodate part-time work. Expertise of
      long-time nurses are especially valuable in QA functions. Expanded pool of talent
      helps offset effects of nursing shortage.

PMID- 14708488
TI  - Translation web site aids broad patient population.
AB  - Consumer health information is available in more than 30 languages. Using family
      members as interpreters raises issues of quality and ethics. Administrative forms
      the first phase; education will follow.

PMID- 14708490
TI  - Lessons learned: what to expect from shared visions--new pathways.

PMID- 14708491
TI  - Cope with lack of control during new survey process.

PMID- 14708492
TI  - What JCAHO's new IC standards mean for you.

PMID- 14708493
TI  - Patient Safety Alert. Pediatrics program just the beginning of safety overhaul.

PMID- 14708494
TI  - Discharge Planning Advisor. Do you offer a choice on home care services?

PMID- 14708495
TI  - Discharge Planning Advisor. Hospitals seeking SNF beds think creatively.

PMID- 14708496
TI  - What to do if physicians dispute your data.

PMID- 14708497
TI  - Get more out of your FMEAs.

PMID- 14708498
TI  - [A simple method to detect disaccharides deficiency].
AB  - A simple method, easy to perform during an endoscopic procedure, fast and
      inexpensive, that allows detecting deficiencies in lactase, sucrase or maltase
      activities is presented. Briefly, method consists in placing a duodenal biopsy
      sample in an adequate vial containing lactose, sucrose or maltose solution during
      a few minutes, and then, adding a few drops of a glucose reactive from commercial
      origin. Presence of any enzymatic activity is demonstrated when released glucose
      from any of the disaccharides chosen reacts with the second reactive, turning
      solution to a red colour. Its utility is discussed and compared with other
      diagnostic methods.

PMID- 14708499
TI  - Evaluation of a liquid urease test (LUT) for detection of Helicobacter pylori.
AB  - The aim of our study was to develop a rapid diagnostic urease test to demonstrate
      the presence of Helicobacter pylori in the Endoscopy room. MATERIALS AND METHODS:
      200 consecutive patients referred to gastroscopy for different indications, were
      included in this study. One antral biopsy sample was obtained to be immersed in
      our test. The same sample was used for histological evaluation, considered to be
      the gold standard method for diagnose of Helicobacter pylori infection. RESULTS:
      135 patients (67.5%) were found positives and 65 patients (32.5%) were negatives
      in our test. 128 patients (64%) showed Helicobacter pylori on histological
      examination. Our test showed a sensitivity of 91%, specificity of 88.1%, and
      positive and negative predictive values of 95% and 80% respectively. A remarkable
      correlation between density of Helicobacter pylori and reading time was also
      observed, where a high density of the bacteria reduced the reaction time in this
      liquid test. Furthermore, an overall accuracy of 90% was shown, which is
      comparable with other available commercial tests. CONCLUSION: LUT is easy to
      handle, cost effective and fast, with a high positive predictive value.

PMID- 14708500
TI  - [History of patients with pelvic floor dysfunction].
AB  - OBJECTIVES: 1) To determine differences between sexes; 2) To determine
      differences by sex and age groups in symptom onset, time of evolution, clinical
      forms and probable associated causes. POPULATION AND SAMPLE: 83 consecutive
      patients with diagnosed PCP (X age = 50.9 SE 2.21). 25 males (30.1% x 51.2 years
      old, SE 4.1) and 58 females (69.9%, X 50.8 years-old, SE 2.2). Patients with
      organic colon-rectum pathology (with the exception of hemorrhoidal pathology,
      proctologic surgery and active anus fissure) had been excluded. METHODS: Colonic
      Double-contrasted Rx, rectum-sigma endoscopy, and eventually a Colonofibroscopy
      Historic facts and syndromic protocol. Diagnosis criteria: 1) Perineal
      inspection: perineal contraction with pujo; 2) Rectal tact; 3) Ano-Rectum
      manometry with perfused system; 4) 150 ml Rectal balloon expulsion dynamic; 5)
      Utoreported signs and symptoms from a cuestionnaire ad hoc. Division into
      evolutive groups (continuous and intermittent). Division by age (< = 5, 5.1-25, >
      25 years old). EXPERIMENT DESIGN: descriptive, comparative, correlation,
      prospective, simple blind. STATISTICS: Levene, descriptive, chi square, ANOVA,
      Kruskall-Wallis, Kendal tau b. RESULTS: 1) Difference in sex proportion was
      significative (p = 0.0001); 2) There were not differences between sexes in age
      media at the moment of the study (p = 0.92; 3) The continue evolutive form
      represented 77.1%, (p = 0.0001) but there weren't differences between sexes (p =
      0.19) There weren't evolutive differences between age groups. (p = 0-78) 4) Age
      of onsec: x = 24.04 years-old, SE 2.02 (4-80 years-old), without differences
      between sexes (p = 0.16). 14.5% started before age of 5, 85% after that age,
      without differences between sexes (p = 0.07); 5) The time of evolution x = 26.7
      years, SE 2.21, without differences between sexes (p = 0.25); 6) Potential causes
      were divides into tree categories: I "the patient doesn't remember associated
      facts" (30.1%, II: psychological or physical stress (39.8%), III: facts related
      to sexual trauma (30.1%). The differences (p = 0.0001); 7) Analyzed in general by
      sec, the most common cause was psychological-physical stress rather than sexual
      trauma in men, while among women sexual trauma was most common than psychological
      physical stress (p = 0.03); 8) Analyzed by age groups: in the under 5 years-old
      group: main cause was "I don't remember". In 5.1-25-years-old group: sexual
      trauma; and psychological-physical stress was the main cause in > 25 years-old
      group (p 0.0001). CONCLUSIONS: 1) Women suffer from or consult much more
      frequently than man; 2) Once the disease is present, there would not be
      differences in age, age of onset, or time or evolution into proportions by sex;
      3) The continue forms were the predominant ones; 4) The probable associated
      causes vary for each age group; 5) The sub-group "I don't remember" could
      represent in many cases a mismatch learning, but not constantly (there are cases
      of stress in familiar context); 6) In the subgroup "late childhood-adolescence"
      the predominant causes were traumatic experiences in erotic zones (rapping
      intent, sexual abuse, fantasies, elimination of parasites by the anus); 7) in the
      subgroup "older than 25 years-old" the predominant causes were physical stress,
      (violence, accidents, surgery) or emotional stress (familiar environment, social
      environment, affective losses). Some paradigmatic cases are presented. Anismus
      would be a complex situation involving an striated, voluntary, automatizated
      muscle (puborectalis) controlling independently genital-sexual, urinary and ano
      rectal functions.

PMID- 14708501
TI  - Steroid-induced cataracts in patients with autoimmune hepatitis.
AB  - BACKGROUND: Posterior subcapsular cataract (PSC) has been reported in patients on
      corticosteroids therapy for various pathologies. Autoimmune hepatitis (AIH) is a
      progressive inflammatory hepatic disease for which corticosteroids are
      recommended but PSC has not yet been reported in AIH patients on corticosteroids
      therapy. METHODS: The AIH patients at our service underwent an ophthalmological
      assessment and their files were analyzed establish the dosage and duration of
      medication, the presence of visual complaints and the type of AIH, in order to
      correlate these with the ophthalmological findings. Patients were examined with a
      slit lamp following pupil dilation. RESULTS: 17 AIH patients evaluated, only one
      patient had PSC. CONCLUSION: Although the frequency of PSC was low (1/17) in AIH
      patients on costicosteroid therapy, these individuals should undergo occasional
      ophthalmological assessment for the presence of cataracts since their visual
      acuity and quality of life may be adversely affected.

PMID- 14708502
TI  - [Agenesis of the gallbladder].
AB  - The agenesis of the gall bladder is a rare congenital abnormality that usually is
      diagnosed as cholecystolithiasis. Therefore it is an intraoperative discovery. In
      this work two new cases are added to casuistry; both them have received
      laparotomic treatment. As those cases were symptomatic patients, the most common
      clinical manifestations are described. We insist in tactics to discard ectopic
      locations and the different options for the intraoperative and postoperative
      study; this last situation seems to be the most used behavior on patients
      approached laparoscopically.

PMID- 14708503
TI  - [Advances in hereditary hemochromatosis].
AB  - Hereditary hemocromatosis (HH) is a genetic disease with a recessive autosomic
      pattern, in which inadequate iron (Fe) absorption is made by the intestinal cell.
      As consequence of that process, takes place a progressive accumulation of metal
      in different organs, predominantly in the liver. This leads to an alteration of
      liver structure and function: cirrhosis and hepatocarcinoma (1). The gene implied
      in this pathology was identified (HFE) in 1996. This codes a similar molecule to
      the mayor histocompatibility complex type 1(MHC-T1 like) that can modulate the
      transport of PE binding the transferrin receptor. This progress allows a deep
      understanding of the molecular and cellular biology of the homeostasis of the Fe
      and its alterations in the NH. The diagnosis of disease by means of a genetic
      test let to carry out a familiar screening and to detect asymptomatic carriers.
      This makes possible to begin the appropriate treatment at early stages of the
      disease in order to avoid its consequences and offering a better quality of life
      to these patients.

PMID- 14708504
TI  - [The medical specialties must to be developed on the biological and
      anthropological scientific bases: integral and individual medicine].

PMID- 14708505
TI  - Use of a polytetrafluoroethylene tube and patch in the repair of a difficult
      duodenal stump.
AB  - In the cases where a primary anastomosis is unable after a duodenal resection,
      special care must be taken to avoid any complication in the duodenal stump such
      as suture dehiscence. Wall inflammation is an important factor in the development
      of this complication. We report a case of a 35-year-old woman who had previously
      undergone to pyloric exclusion due to a wall defect occurred after a bilio
      digestive anastomosis, which complicated with a posterior duodenal stump
      dehiscence. The acute edema of the stump walls that resulted after it because
      exposure to bile conducted to heroic measures for its closure: first, the use of
      a polytetrafluoroethylene tube as duodenostomy and posteriorly a patch of the
      same material for its final closure. Both gave successful results in the repair
      of a refractory duodenal stump dehiscence.

PMID- 14708507
TI  - [Most frequent causes of constipacion in our environment].
AB  - At the Digestive Motility Department on gastroenterology floor of the "Hospital
      de Clinicas Jose de San Martin", 165 patients were evaluated due to chronic
      constipation, underlying the most frequent causes in our environment. The use of
      the present diagnostic methods is suggested following a suitable clinical
      orientation. The most frequent causes of constipation after this test were:
      chronic idiopathic constipation in 112 cases (67.87%) and with megarectum,
      megasigma and megacolon 32 cases (19.09%), rectocele in 9 cases (5.45%), rectal
      prolapse in 5 cases (3.03%), enf. De Hirschprung 5 cases (3.03%) and anal
      estenosis 2 cases (1.21%).

PMID- 14708506
TI  - [Functional Dyspepsia and infection by Helicobacter pylori: a causal relation
      does not exist].
AB  - The role of Helicobacter pylori (Hp) in Non Ulcer Dyspepsia (NUD) has been a
      controversial issue. OBJECTIVES: 1) To determine the frequency of Upper
      Gastrointestinal Endoscopy (UGE) in patients suffering NUD in whom endoscopy was
      indicated in our Service, 2) To determine the prevalence of infection by Hp in
      patients with NUD in whom endoscopy was done, 3) To find an association of
      clinical and historical facts among patients with and without Hp infection.
      POPULATION AND SAMPLE: 91 consecutive patients, free of esophageal or gastro
      intestinal organic disease by endoscopic criteria from a total of 132, in a
      period of six months. 47 men (X age: 50.4 years, SE 2.6, SD 17.3) and 44 women (X
      age 49.7 years, SE 2.5, SD 16.8), Levene's Test p = 0.91. Descriptive,
      comparative and correlation, transverse simple-blind. METHODS: 1) two endoscopic
      biopsies for Hp (antrum and corpus), Rapid Hp Urease Test (modified Christensen
      protocol) with immediate and 6-hours later readings; 2) two samples for
      histopathologic diagnosis of Hp (antrum and corpus) with H&E, Giemsa or Warthin
      Starring. STATISTICS: Levene Test for homogeneity of variance, descriptive
      statistic tests, ANOVA, chisquare, contingency coefficient, Pearson's "r", Run
      Tests. Alpha level = 0.05. RESULTS: 91 out 132 patients were included (69.9%).
      Prevalence was greater in men (p = 0.04). "Run Tests" for variables between 0.34
      and 0.76, 45 patients were positives (+) for one or two methods (49.5%). There
      were significative differences between the means for variable "age" for the
      groups (+) and (-) at the moment of the study (+, mean age 45 years old, SE 2.4;
      negative tests, mean age 55 years old, SE 2.5, p = 0.005). Wide data dispersion
      (Coefficient of Pearson = 34.5%). There was association between age symptoms
      onset and positive tests (mean 40.4 years old, SE 2.6, Coefficient of Pearson
      43%) and negative tests (mean 48.9 years old, SE 2.6, Coefficient of Pearson 36%)
      (p = 0.02). There were also association between age and + tests (p = 0.005). Non
      statistically significant differences were found between time of evolution of
      symptoms (p = 0.49), prevalence between sexes of symptoms (although nearly
      significant, p = 0.06), presence of unespecific pain (p = 0.16), ulcer-like pain
      (p = 0.46), plenty sensation, distension, satiety (p = 0.64) and differences by
      sex and age in symptoms (p = 0.55). CONCLUSIONS: 1) There would be an
      overestimation of UGE value in presumable dyspeptic patients, 2) Prevalence of
      infection agrees with the published values in equivalent populations in our
      country, 3) Pinfection prevalence was greater in men. 4) It could exist
      significative differences between age of symptoms onset in infected group
      (earlier symptoms) and means of age (younger infected people at the moment of
      this study), but there were very wide data dispersion), 5) Association between
      age and positiveness would be explained because it would be an accumulative
      phenomenon noted by us in a previous study 6) There wouldn't be enough evidence
      to consider Hp infection to be the cause of NUD.

PMID- 14708508
TI  - [Gastric cancer: an unusual presentation].
AB  - We want to introduce the case of an 18 year old male patient who consulted us
      because of proctorrhage, straining and rectal tenesmus. Diagnosis was rectal
      tumor which pathological anatomy revealed an adenocarcinoma of cells in seal ring
      shape, suggesting a probable gastric origin. The high endoscopy evidenced
      multiple polyps, less than a centimeter wide found in the cardiac orifice, body
      and antrum, with the same histology. All these findings were confirmed during the
      exploratory laparotomy. We thought it was interesting to report this case because
      of the clinical presentation, unusual in this type of gastric cancer.

PMID- 14708509
TI  - [Acute fatty liver during pregnancy: report of case].
AB  - Acute fatty liver during pregnancy constitutes a rarely clinical entity with
      unknown pathogenesis and etiology. Its clinical picture is similar to
      preeclampsia including liver failure manifestations. Here in me expose a clinical
      case of a young woman 35 week first pregnancy with mild preeclampsia symptoms. We
      include a review of the literature.

PMID- 14708510
TI  - [Antibiotics effects on intestinal flora: its modifications with the antibiotics
      used in the clinical practice of gastroenterology].
AB  - This is an analytical of changes that antibiotics cause on intestinal-microflora
      with special attention to the antibiotics used in the clinical practice of
      gastroenterology. We wish to special attention to antibiotics such as
      metronidazole, clarithromycin, fluoroquinolone, cephalosporin and imipenem. In
      each case changes produce by this drug and microbial resistance are analyzed. A
      prudential and justified use of this group of antibiotics is suggested.

PMID- 14708511
TI  - K-ras as a genetic marker in pancreatic cancer.

PMID- 14708513
TI  - Hip protectors: another useful report from Finland.

PMID- 14708512
TI  - Caroli's disease: 6 case studies.
AB  - Caroll's disease is characterized by congenital non-obstructive dilatation of the
      intrahepatic bile ducts of undefined etiology. It is a rare disease usually
      affecting the whole liver but it may affect a lobe or a segment (11). This study
      shows the evolution of 6 cases (2 boys and 4 giris) that were diagnosed with
      Caroli's disease at a referral service. Their ages ranged from 2 to 16 years-
      median age 10 years. One of the patients presented with cholangitis, while
      hepatomegaly was observed in 83% of the cases. Four of the patients presented
      biliary lithiasis and in one of these cholesterol crystals could be observed in
      the duodenal secretion. The diagnosis was confirmed in 4 cases by endoscopic
      retrograde cholangiopancreatography, in 1 by cholangioresonance and 1 by
      echography. Two of the patients also presented congenital hepatic fibrosis. The
      outpatient clinic follow-up indicated that all the patients evolved well with the
      exception of one patient who was selected as a candidate for liver
      transplantation.

PMID- 14708514
TI  - Consensus report IASLC workshop Bruges, September 2002: pretreatment minimal
      staging for non-small cell lung cancer.

PMID- 14708515
TI  - Critical factors for patient management.
AB  - The main critical factors for lung cancer patient management, apart from TNM
      staging, include expertise required to offer optimal management and conditions
      related to the patient, including performance status and weight loss and the
      presence of lung, cardiac or other comorbidities. Performance status and weight
      loss must be assessed for all patients. The minimal pulmonary functional
      evaluation should include spirometry. The minimal cardiac evaluation should
      consist of a clinical history and evaluation for cardiac risk factors and disease
      and at least preoperatively, and ECG. Age per se is not a contraindication for
      curative treatment.

PMID- 14708516
TI  - Induction treatment before surgery for non-small cell lung cancer.
AB  - Surgery alone is currently still accepted "standard of care" for patients with
      operable NSCLC, this includes stages IA and IIB, as well as selected early
      subsets of IIIA disease. In more advanced and inoperable stage III disease,
      combinations of chemotherapy and radiotherapy remain the standard treatment
      approach for patients with good performance status. The role of surgery following
      induction therapy in these advanced stage III patients is at the moment not
      conclusively defined. More evidence from randomized trials is clearly needed to
      tailor treatment for the large number of patients that present in these locally
      advanced stages. Enrollment of patients into ongoing prospective clinical trials
      should be encouraged, whenever possible, to further define prognostic factors and
      improve multimodality strategies in this clinical setting.

PMID- 14708517
TI  - What's new on the dental scene? Browsing through the dental literature.

PMID- 14708518
TI  - Management of unresectable non-small cell carcinoma of the lung (NSCLC).

PMID- 14708519
TI  - Consensus: the follow-up of the treated patient.
AB  - This is the first consensus document on the follow-up of the treated patient with
      non-small cell lung cancer that has been written by this group. The document has
      been drawn up by doctors coming from many different cultures and philosophical
      backgrounds. It acknowledges that there are published guidelines on the follow-up
      particularly those in trials, and does not wish to contradict these. There is
      lack of evidence-based medicine to recommend a strong general policy in this
      area. For those patients who were treated with curative intent the initial follow
      up will depend upon the toxicity that is evident from the treatment given.
      Thereafter the interval between follow-up visits should be every 3 months for the
      first two years, then every 6 months for up to five years. Rapid and easy access
      to the multidisciplinary team should be available. Full examination and chest X
      ray should be carried out on each visit but other investigations should be
      determined by clinical need. For those patients treated with palliative intent
      the interval between follow-up visits once the acute reactions have settled will
      depend upon the adequacy of the control of the symptom and the availability of
      separate palliative care teams. At all times the patient should have rapid access
      to the multidisciplinary team and in general frequent follow-up, that is at
      intervals of one to two months, may be appropriate during the first six months.
      Follow-up constitutes an important part of lung cancer management. Efforts should
      be made to gain clinical material to give us evidence-based guidelines.

PMID- 14708520
TI  - [DGSP-Congress: Smart atheletes lean forward].

PMID- 14708521
TI  - [Iontophoreses in physical therapy: reality or fiction?].

PMID- 14708523
TI  - [Diseases of the eye surface].

PMID- 14708522
TI  - Sensitivity to human serum of gammaretroviruses produced from pig endothelial
      cells transduced with glycosyltransferase genes.
AB  - Reduction of pig cell-surface alpha-galactosyl (Gal) epitope, Galalpha1,
      3Galbeta1, 4GlcNAc-R, by the introduction of glycosyltransferase genes is
      effective in suppressing hyperacute rejection (HAR) in pig-to-human
      xenotransplantation. The transmission of porcine endogenous retroviruses (PERVs)
      has been recognized as a potential risk factor associated with
      xenotransplantation. In this study, effects of the introduction of
      glycosyltransferase genes to pig cells on the sensitivity of gammaretroviruses to
      human serum were investigated. Pig endothelial cells (PEC), PEC transduced with
      alpha1,2 fucosyltransferase (FT), alpha2,3 sialyltransferase (ST), or N
      acetylglucosaminyltransferase III (GnT-III), and human embryonic kidney (HEK) 293
      cells were transduced with the LacZ gene with the packaging signal of murine
      leukemia virus (MuLV) under the control of the long terminal repeat of MuLV by a
      pseudotype infection. Then, the cells were further infected with PERV subtype B
      (PERV-B) or feline leukemia virus subgroup B (FeLV-B). Culture supernatants of
      the infected cells were mixed with human serum (HS) and then inoculated to HEK293
      cells. The inoculated cells were histochemically stained and lacZ-positive blue
      foci were counted. Glycosyltransferase activity, xenoantigenicity, and alpha-Gal
      epitope density in the cells were measured at the time of the infection
      experiments. PERV-B or FeLV-B particles from the parental PEC were efficiently
      neutralized by HS, while those from PEC transduced with alpha1,2FT, alpha2,3ST or
      GnT-III were less sensitive to HS. The transduced PEC exhibited high levels of
      activity of the introduced glycotransferases, and expressed fewer xenoantigens
      and cell-surface alpha-Gal epitopes. Our results suggest that gammaretroviruses
      including PERVs produced by transgenic pigs, that are generally modified to
      reduce the cell-surface alpha-Gal epitope to overcome the HAR in
      xenotransplantation, are less sensitive to HS.

PMID- 14708524
TI  - Transmission of porcine encephalomyocarditis virus (EMCV) to mice by
      transplanting EMCV-infected pig tissues.
AB  - We recently demonstrated that pigs infected with porcine encephalomyocarditis
      virus (EMCV) develop a persistent infection (up to 90 days post-infection (PI))
      in the heart and brain that is accompanied by virus-induced pathologic changes,
      and that EMCV productively infects human cardiomyocytes in vitro, suggesting that
      EMCV may pose a risk to humans following transplantation of pig tissues to humans
      (Brewer et al. J Virol 2001; 75: 11621-11629). In this report, we demonstrate
      that intra-abdominal of myocardial or pancreatic sections from acutely-EMCV
      infected pigs (2 days PI) in either non-mutant C57BL/6 or C57BL/6-RAG-1-/- mice
      that lack B or T lymphocytes, resulted in transmission of the virus and acute
      fatal disease in all mice. In recipient RAG-1-/- mice, fatal EMCV disease
      occurred within 2 days post-transplantation, and it was accompanied by high virus
      titers in brain, heart, liver, spleen, kidneys and skeletal muscle, whereas in
      non-mutant C57BL/6 mice, disease occurred 5 to 6 days post-transplantation and
      was accompanied by lower virus titers. Transplantation of myocardial or
      pancreatic tissues from chronically EMCV-infected pigs (21 and 50 days PI) did
      not induce clinical disease, but resulted in detection of EMCV RNA in the brain
      of recipient RAG-1-/- mice, no viral RNA was detected in non-mutant C57BL/6 mice.
      Intra-abdominal transplantation of uninfected porcine myocardial tissues into RAG
      1-/- mice followed by intramuscular inoculation with EMCV induced acute clinical
      disease but did not result in transmission of virus to the xenograft. These
      results show that EMCV can be efficiently transmitted from pig myocardial and
      pancreatic tissues to mice, providing a model of pig-to-human viral xenozoonosis
      that can be used to develop and test prophylactic and therapeutic measures
      against such infection.

PMID- 14708525
TI  - [Glaucoma and uveitis. Causes of and treatment options for increased intraocular
      pressure in cases of inflammatory ophthalmology].
AB  - Uveitic secondary glaucoma poses one of the most difficult problems for
      differential diagnostics and therapeutics in the field of clinical
      glaucomatology. The prevalence of glaucoma among uveitis patients ranges between
      5 and 20% with great fluctuations depending on the underlying disease, duration
      of the disease, and the patient's age. Based on slit-lamp examination, uveitis
      can be classified as granulomatous and non-granulomatous. The effects of uveitic
      glaucoma on the quality of life and central visual acuity are particularly
      serious during childhood. Surgical reduction of eye pressure in cases of uveitic
      secondary glaucoma should only be performed if medical treatment of the
      underlying disease or ocular inflammation does not lower the eye pressure level
      and if in the presence of glaucomatous damage to the optic nerve the level of
      intraocular pressure is so high that a drastic decrease in pressure that cannot
      be achieved by medication becomes necessary.

PMID- 14708526
TI  - Long-term survival of neonatal porcine Sertoli cells in non-immunosuppressed
      rats.
AB  - Sertoli cells from the testis contain immunoprotective properties which allow
      them to survive as allografts and also to protect islets and adrenal chromafin
      cells from immune rejection without the use of immunosuppressive drugs.
      Experiments were designed to determine whether xenogeneic neonatal porcine
      Sertoli cells (NPSCs) survive transplantation in rats without the use of
      immunosuppression. NPSCs (92.2 +/- 5.1%) were isolated, cultured and then
      transplanted under the kidney capsule of non-immunosuppressed Lewis rats. To
      assess survival, grafts were removed after 4, 20, 30, 40, 60, and 90 days post
      transplant and immunostained for the Sertoli cell marker vimentin. Survival was
      confirmed by polymerase chain reaction (PCR) for the porcine mitochondrial
      cytochrome oxidase II (COII) subunit gene, a marker for porcine tissue. In both
      methods, NPSCs were detected in the grafts for at least 90 days. Histologically,
      NPSCs were clustered in small aggregates or organized in tubule-like structures.
      When stained for the presence of proliferating cell nuclear antigen (PCNA), many
      Sertoli cells stained positive at 20 days post-transplant, indicating not only
      cell survival but also Sertoli cell proliferation. The number of PCNA positive
      cells decreased somewhat by 40 days with almost no positive Sertoli cells at 60
      and 90 days. These data demonstrate that NPSCs survive long-term following
      xenotransplantation in rats, which to our knowledge is the first report of a
      discordant xenograft surviving without immunosuppression in a non
      immunoprivileged site. Further study of the mechanism of NPSC xenograft survival
      may provide clues for promoting a local tolerogenic environment.

PMID- 14708527
TI  - Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey
      renal xenotransplantation.
AB  - Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent
      xenotransplantation models, but the data generated so far with MTX in pig-to
      baboon cardiac transplantation studies have been disappointing. The potential of
      this agent was consequently explored in a life-supporting pig-to-primate renal
      model using the cynomolgus monkey as the recipient species. Introductory in vitro
      and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted
      in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a
      life-supporting kidney from human decay-accelerating factor transgenic pigs were
      administered MTX intravenously according to three different regimens. All the
      animals also received cyclosporine A and steroids. In addition, mycophenolate
      sodium (MPS) was administered post-operatively in two of the three groups of
      transplanted animals. At clinically relevant concentrations, MTX is able in vitro
      to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After
      intravenous administration, moreover, exposure of cynomolgus monkeys to MTX
      appeared to be higher than had been previously reported in baboons. Graft
      function was observed in the transplanted animals, which survived from 0 to 41
      days. All but two animals revealed acute humoral rejection in the explanted graft
      and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It
      was unrelated to the administration of MPS and associated with severe
      histopathological signs of enteritis. This study demonstrates that the
      pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between
      non-human primate species. In vitro, MTX has immunosuppressive properties in the
      cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very
      narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons.
      We conclude that MTX is scarcely effective as an immunosuppressant, be it for
      induction or maintenance, in pig-to-cynomolgus monkey renal xenotransplantation.

PMID- 14708528
TI  - IgM-enriched human introvenous immunoglobulin strongly inhibits complement
      dependent porcine cell cytotoxicity mediated by human xenoreactive antibodies.
AB  - Treatment with intravenous immunoglobulin preparations consisting of human IgG
      (IVIgG) prevents hyperacute rejection of pig xenografts transplanted into
      primates by inhibition of the classical complement pathway. Recent studies
      indicate that IVIg preparations mainly consisting of human IgM (IVIgM) have a
      stronger capacity than IVIgG to inhibit the complement system. IVIg preparations
      also contain xenoreactive antibodies (XAb) binding to pig cells. In the present
      study, we compared IVIgG and IVIgM for their capacity to inhibit xenogeneic
      complement activation, with special reference to the roles of IgG and IgM XAb
      present in these preparations. Xenogeneic complement activation was studied by
      exposure of pig cells (PK15) to human serum. For some experiments, IVIgG and
      IVIgM were depleted from XAb by immune absorption. Exposure of PK15 cells to
      human serum induced surface deposition of C4 and C3 and cytotoxicity, which could
      be inhibited in a dose-dependent fashion by both IVIgM and IVIgG. The efficacy of
      IVIgM was more than 10 times higher than that of IVIgG. IgG XAb were detected
      IVIgG and IVIgM whereas IgM XAb were only present in IVIgM. Depletion of XAb from
      the IVIg preparations did not modify the protective properties of IVIgG against
      cytotoxicity induced by human serum, whereas the IVIgM-mediated protection
      against xenogeneic cytotoxicity was only slightly improved. IgM-enriched IVIg is
      a potent inhibitor of xenogeneic complement activation and complement-dependent
      cytotoxicity of human serum to pig cells, irrespective of the presence of
      cytotoxic xenoreactive IgM antibodies in this preparation. Therefore, IVIgM has a
      promising therapeutic significance for the treatment of (hyper)acute xenograft
      rejection.

PMID- 14708529
TI  - Pig kidney transplantation in baboons treated intravenously with a bovine serum
      albumin-Galalpha1-3Gal conjugate.
AB  - The maintenance of depletion of antibody (Ab) reactive with Galalpha1-3Gal (Gal)
      on pig vascular endothelial cells by the intravenous (i.v.) infusion of a
      synthetic Gal conjugate has been proposed as a means of delaying Ab-mediated
      rejection of transplanted pig organs in primates. We have therefore studied the
      effect of the continuous i.v. infusion of bovine serum albumin conjugated to
      multiple synthetic Gal type 6 oligosaccharides (BSA-Gal) on anti-Gal Ab levels
      and on graft survival in baboons undergoing pig kidney transplantation. Group 1
      baboons (n=3) underwent extracorporeal immunoadsorption of anti-Gal Ab, a
      cyclophosphamide (CPP)-based immunosuppressive regimen, and a non-transgenic pig
      kidney transplant. Group 2 (n=2) were treated identically to Group 1 but, in
      addition, received a continuous i.v. infusion of BSA-Gal. Group 3 (n=2) were
      treated identically to Group 2, but without CPP. A single baboon (Group 4)
      underwent extracorporeal immunoadsorption, a CPP-based regimen, and continuous
      i.v. BSA-Gal therapy for 28 days, but did not receive a pig kidney transplant.
      Two of the transplanted pig kidneys in Group 1 were excised on post transplant
      days 7 and 13 for a rejected ureter, and disseminated intravascular coagulation
      (DIC), respectively. The third baboon died of sepsis on day 6. All transplanted
      ureters and kidneys showed some histopathologic features of acute humoral
      xenograft rejection. Group 2 baboons were euthanized on days 8 and 11,
      respectively, for liver failure. At autopsy, there were histopathological
      features of widespread liver necrosis, but the pig kidneys and ureters showed no
      features of rejection. The pig kidneys in Group 3 baboons were excised for renal
      vein thrombosis (day 9) and DIC (day 12); there was no histological signs of
      rejection in the pig kidneys or ureter, although there were focal areas of modest
      liver injury in one baboon on biopsy. The single Group 4 baboon showed no
      biochemical or histological features of liver injury. Anti-Gal Ab levels returned
      in Group 1, but were maintained at negligible levels in the baboons in Groups 2
      to 4 that received BSA-Gal therapy. Continuous i.v. therapy with BSA-Gal is
      largely successful in maintaining depletion of circulating anti-Gal antibodies
      and in preventing or delaying Ab deposition and acute humoral xenograft rejection
      in porcine grafts, but may be associated with liver injury when administered in
      the presence of a pig kidney transplant and CPP therapy. The mechanism of the
      hepatic injury remains uncertain.

PMID- 14708530
TI  - The role  of glutathione in intestinal dysfunction.
AB  - Glutathione plays an important cytoprotective role in the gut. Animal studies
      have demonstrated that the provisions of glutathione precursors are protective
      for different types of free-radical-mediated cellular injury. There is a need to
      clarify the potential role of glutathione supplementation in ischemia-reperfusion
      injury and inflammatory bowel disease. More speculative is whether treatment with
      glutathione precursors can modify the progress of colorectal cancer.

PMID- 14708531
TI  - CD46 protects pig islets from antibody but not cell-mediated destruction in the
      mouse.
AB  - We have previously reported that islets present in cultured fetal pig pancreas
      (FPP) are resistant to destruction by Galalpha(1,3)Gal antibodies and compliment,
      but are susceptible to the 'secondary' antibody response which occurs on
      transplanting pig islet tissue to Galo/o murine recipients. In a model of
      antibody-mediated graft rejection, we tested the resistance of porcine islets to
      antibody. Using FPP from human CD46 transgenic pigs, we now report that the
      complement regulator, CD46, affords protection from antibody-mediated rejection
      when mouse anti-pig serum (MAPS) was administered to scid mice bearing PFF grafts
      from either CD46 transgenic or normal pigs. Indeed, whereas normal pig islets
      were destroyed by an intraperitoneal (i.p.) injection of 0.1 to 0.2 ml of MAPS
      antibody, destruction of CD46-expressing transgenic islets required 0.5 ml, i.e.
      up to five times the amount. In contrast, there was no prolongation of the
      survival of CD46 transgenic mouse skin or heart major histocompatibility complex
      compatible or -incompatible allografts--rejected by predominantly cellular immune
      mechanisms, as opposed to xenograft rejection. Although complement regulators
      have been examined for their protective role in hyperacute rejection of
      vascularized xenografts, it is clear that they also have protective effects in
      the later, antibody-mediated responses, but are unlikely to effect the
      inflammatory response in cell-mediated rejection.

PMID- 14708532
TI  - Porcine pancreatic icosapeptide as a marker of graft survival and rejection in
      xenotransplantation.
AB  - The previous study showed that it is possible to monitor the viability of
      xenografted fetal pig pancrease in the first 3 weeks after transplantation in a
      normoglycemic immunoincompetent mouse [1]. This is achieved by measuring serum
      levels of porcine pancreatic icosapeptide (PI) in the host using a specific
      immunoassay. PI is secreted from the pancreatic polypeptide (PP) cell, the first
      mature endocrine cell of the fetal pig pancreas. Insufficient insulin is produced
      by the graft at this time to use it as a marker of graft viability. We have now
      examined the usefulness of PI to monitor graft survival in diabetic
      immunoincompetent mice and in immunosuppressed mice. Fetal porcine pancreatic
      tissue was transplanted beneath the renal capsule of streptozotocin-diabetic non
      obese diabetic severe combined immunodeficient mice (NOD-SCID) and BALB/c mice
      given cyclosporin (CsA) for 21 or 10 days, respectively. Blood and grafts were
      analyzed periodically over 15 and 3 weeks, respectively, for porcine PI and C
      peptide/insulin. In the diabetic mice, porcine PI was detected in sera up to 2
      weeks following transplantation and was absent thereafter. Serum porcine C
      peptide was detectable at 3 weeks and reached maximum levels at 12 to 15 weeks.
      PI content of the grafts was highest at day 4 and 3 weeks and lowest from 9 weeks
      onwards while insulin levels in the graft were highest from 9 weeks onwards. In
      BALB/c mice immunosuppressed with CsA, serum PI was detectable for 21 days. In
      the mice given CsA only for 10 days, serum PI was detectable for that time, but
      not on day 14 although PI was detectable in the graft. In mice given no CsA, PI
      was undetectable in serum at any time although PI was present in the graft at day
      4. The presence of porcine PI in sera is a marker of graft survival of fetal
      porcine pancreatic tissue in diabetic immunocompetent mice in the first 2 weeks
      after transplantation. Its absence in immunosuppressed mice in this period is an
      early indicator of graft rejection.

PMID- 14708533
TI  - PCA by proxy: minimizing the risks.

PMID- 14708534
TI  - Fas deficiency exacerbates cerulein-induced pancreatitis.
AB  - Acute pancreatitis results in many deaths each year. Our understanding of
      pathophysiology is limited. To better understand the impact of apoptosis versus
      necrosis, we compared cerulein-induced pancreatitis in Fas-deficient (MRL
      lpr/lpr) versus Fas-sufficient (MRL +/+) mice. Average amylase values in Fas
      deficient mice were substantially greater than in Fas-sufficient mouse. Histology
      graded on edema, inflammation, vacuolization, and necrosis showed greater injury
      in the Fas-deficient mouse. This finding suggests that the Fas pathway is
      important in controlling cerulein-induced pancreatitis.

PMID- 14708539
TI  - Using ultrasound to guide PICC insertion.

PMID- 14708540
TI  - Delivering the verdict.

PMID- 14708541
TI  - Identifying infective endocarditis.

PMID- 14708542
TI  - Effect of ulcerative colitis in the bursting strength of colonic anastomoses in
      rats.
AB  - Inflammatory bowel disease may have a deleterious effect on bowel healing, but
      its role is difficult to demonstrate in clinical practice because of the
      association of multiple factors. An experiment was conducted in rats. They were
      divided into two groups: group I, a model of acetic acid induced colitis, and
      group II, the control group. Both groups underwent a rectal resection and primary
      anastomosis. On postoperative day 7, the bursting strength of the anastomosis was
      evaluated. There were 44 rats in group I and 38 in group II. In 91% of group I
      rats there were histopathological changes compatible with inflammatory bowel
      disease (IBD). Mean bursting pressure was significantly reduced in rats with
      acetic-acid induced IBD (142.18 +/- 18.22 mm Hg in group I, and 208.85 +/- 14.8
      mm Hg in group II; p < .05). These results suggest the deleterious effect of IBD
      on bowel healing.

PMID- 14708543
TI  - Identifying primary skin lesions.

PMID- 14708544
TI  - Using A1C to gauge blood glucose control.

PMID- 14708545
TI  - Gabexate mesilate (FOY) inhibition of amylase and phospholipase A(2) activity in
      sow pancreatic juice.
AB  - We designed this study in sows to investigate the enzyme inhibitory action of
      gabexate mesylate (GM) directly in the pancreatic juice. We studied 16 sows, each
      weighing about 130 kg. The pancreatic duct was identified and cannulated to
      collect the pancreatic juice. Sows in the treated group received intravenous GM
      infusion at a dose of 1000 mg over 24 h. Control sows underwent the same sampling
      schedule while receiving physiological solution. GM inhibited the two pancreatic
      enzymes amylase and phospholipase A(2) (PA(2)) in pancreatic juice. Thus, the
      enzyme inhibition in the pancreatic gland itself and the central role of (PA(2))
      inhibition in enzyme cascade responsible for activating other proteases confirm
      the therapeutic use of GM in acute pancreatitis.

PMID- 14708546
TI  - Myths & facts...about hemophilia.

PMID- 14708548
TI  - Intravenous infusion anesthesia with Propofol-Midazolam-fentanyl for experimental
      surgery in swine.
AB  - There is a need for prolonged anesthesia procedures in experimental surgery.
      Animals in this study received fentanyl, Midazolam, and Propofol administered by
      continuous intravenous infusion for anesthesia along with controlled ventilation.
      Time of anesthesia was 413 +/- 95 min. Animals could be extubated 20 +/- 12 min
      after operation. Animals recovered completely from anesthesia by day 1 after
      surgery with almost normal physical activity. This study clearly shows that
      intravenous infusion anesthesia is safe and easy to handle in prolonged
      anesthesia for experimental surgery in swine. This anesthetic protocol can also
      be used for intraoperative transportation.

PMID- 14708549
TI  - High positive supercoiling in vitro catalyzed by an ATP and polyethylene glycol
      stimulated topoisomerase from Sulfolobus acidocaldarius.
AB  - A topoisomerase able to introduce positive supercoils in a closed circular DNA,
      has been isolated from the archaebacterium Sulfolobus acidocaldarius. This
      enzyme, fully active at 75 degrees C, performed in vitro positive supercoiling
      either from negatively supercoiled, or from relaxed DNA in a catalytic reaction.
      In the presence of polyethylene glycol (PEG 6000), this reaction became very fast
      and highly processive, and the product was positively supercoiled DNA with a high
      superhelical density (form I+). Very low (5 - 10 micromoles) ATP concentrations
      were sufficient to support full supercoiling; the nonhydrolyzable analogue
      adenosine-5' -0-(3-thiotriphosphate) also sustained the production of positive
      supercoils, but to a lesser extent, suggesting that ATP hydrolysis was necessary
      for efficient activity. Nevertheless, low residual of positive supercoiling
      occurred, even in the absence of ATP, when the substrate was negatively
      supercoiled. Finally, the different ATP-driven topoisomerizations observed, i.e.,
      relaxation of negative supercoils and positive supercoiling, in all cases
      increased the linking number of DNA in steps of 1, suggesting the action of a
      type I, rather than a type II topoisomerase.=

PMID- 14708550
TI  - Legal strategies to reduce tobacco-caused disease.
AB  - In efforts to control diseases it is common to look at ways to control the
      vectors of disease. When dealing with tobacco-caused disease this requires an
      understanding of the companies that manufacture and market tobacco products, and
      an examination of how to shape the behaviour of these companies. Since these
      corporations are created by law, and seek to maximize value for their owners
      within the constraints that laws place on the marketplace, it is only natural
      that a very significant part of tobacco control activities will consist of legal
      strategies. This paper identifies the underlying public health goal of tobacco
      control activities as being the reduction of death and disease. It then considers
      the roles that prevention, cessation, protection from environmental tobacco smoke
      and toxicity reduction can play as overall strategies for achieving this goal.
      This is followed by the identification of a broad range of legal strategies,
      primarily emphasizing governmental regulation, that can be used as part of these
      overall strategies. The paper looks specifically at a range of measures that
      impact on the accessibility of tobacco products, the provision of information for
      consumers, protection of the health and rights of non-users and the significant
      potential health gains from regulation of tobacco products.

PMID- 14708551
TI  - Smokeless tobacco and health in India and South Asia.
AB  - South Asia is a major producer and net exporter of tobacco. Over one-third of
      tobacco consumed regionally is smokeless. Traditional forms like betel quid,
      tobacco with lime and tobacco tooth powder are commonly used and the use of new
      products is increasing, not only among men but also among children, teenagers,
      women of reproductive age, medical and dental students and in the South Asian
      diaspora. Smokeless tobacco users studied prospectively in India had age-adjusted
      relative risks for premature mortality of 1.2-1.96 (men) and 1.3 (women). Current
      male chewers of betel quid with tobacco in case-control studies in India had
      relative risks of oral cancer varying between 1.8-5.8 and relative risks for
      oesophageal cancer of 2.1-3.2. Oral submucous fibrosis is increasing due to the
      use of processed areca nut products, many containing tobacco. Pregnant women in
      India who used smokeless tobacco have a threefold increased risk of stillbirth
      and a two- to threefold increased risk of having a low birthweight infant. In
      recent years, several states in India have banned the sale, manufacture and
      storage of gutka, a smokeless tobacco product containing areca nut. In May 2003
      in India, the Tobacco Products Bill 2001 was enacted to regulate the promotion
      and sale of all tobacco products. In two large-scale educational interventions in
      India, sizable proportions of tobacco users quit during 5-10 years of follow-up
      and incidence rates of oral leukoplakia measured in one study fell in the
      intervention cohort. Tobacco education must be imparted through schools, existing
      government health programmes and hospital outreach programmes.

PMID- 14708552
TI  - The airway epithelium: structural and functional properties in health and
      disease.
AB  - The major function of the respiratory epithelium was once thought to be that of a
      physical barrier. However, it constitutes the interface between the internal
      milieu and the external environment as well as being a primary target for inhaled
      respiratory drugs. It also responds to changes in the external environment by
      secreting a large number of molecules and mediators that signal to cells of the
      immune system and underlying mesenchyme. Thus, the epithelium is in a unique
      position to translate gene-environment interactions. Normally, the epithelium has
      a tremendous capacity to repair itself following injury. However, evidence is
      rapidly accumulating to show that the airway epithelium of asthmatics is abnormal
      and has increased susceptibility to injury compared to normal epithelium. Areas
      of detachment and fragility are a characteristic feature not observed in other
      inflammatory diseases such as COPD. In addition to being more susceptible to
      damage, normal repair processes are also compromised. Failure of appropriate
      growth and differentiation of airway epithelial cells will cause persistent
      mucosal injury. The response to traditional therapy such as glucocorticoids may
      also be compromised. However, whether the differences observed in asthmatic
      epithelium are a cause of or secondary to the development of the disease remains
      unanswered. Strategies to address this question include careful examination of
      the ontogeny of the disease in children and use of gene array technology should
      provide some important answers, as well as allow a better understanding of the
      critical role that the epithelium plays under normal conditions and in diseases
      such as asthma.

PMID- 14708553
TI  - Continuous positive airway pressure therapy in sleep apnoea.
AB  - Sleep apnoea is associated with increased mortality and morbidity. The treatment
      goal is to reduce the neurocognitive and cardiovascular sequelae. CPAP therapy in
      sleep apnoea is discussed in two parts in the article. The first part will
      consider CPAP therapy in the more common form of sleep apnoea (i.e. obstructive
      or mixed sleep apnoea) and the second part will consider CPAP therapy in central
      sleep apnoea. Alternative positive airway pressure modalities are discussed. CPAP
      therapy has been extensively studied and it remains the mainstay of treatment in
      obstructive sleep apnoea, as it is still the most consistently efficacious and
      safe option. However, its major disadvantage is that it does not confer a cure to
      this disorder and hence therapy is generally life long with its usual treatment
      compliance problems. As such, there are continuous improvement strategies. The
      role of CPAP therapy in central sleep apnoea is more limited. There has been
      increasing data on the beneficial effect of CPAP on central sleep apnoea/Cheyne
      Stokes respiration in congestive heart failure. Evidence for CPAP therapy in
      sleep apnoea has evolved significantly over the last decade. However, more
      research and publication of large-scale long-term randomized trials of treatment
      in sleep apnoea to assess patient-orientated outcomes and preferences are
      necessary.

PMID- 14708554
TI  - Progressive form of pulmonary Langenharns' cell histiocytosis in a female adult
      non-smoker.
AB  - Little is known about the cause, nature, treatment and prognosis of pulmonary
      Langerhans' cell histiocytosis (LCH) in adults. We report the case of a 44-year
      old female non-smoker suffering from pulmonary histiocytosis who after a 7-year
      remission period relapsed with both lung and bone disease. Using a combination of
      corticosteroids, methotrexate and bone irradiation treatment, the patient
      achieved total disease remission. The patient was a non-smoking female who has
      had long-term and swift remission of the disease on two occasions.

PMID- 14708555
TI  - Chronic eosinophilic pneumonia associated with Schizophyllum commune.
AB  - We describe the first known Japanese patient with chronic eosinophilic pneumonia
      caused by Schizophyllum commune. The patient presented to Social Insurance Tagawa
      Hospital, Fukuoka, Japan with cough, wheezing, dyspnoea, and fever. Computed
      tomograms of the chest showed bilateral areas of consolidation with air
      bronchograms as well as interstitial infiltrates in the upper lobe, without
      ectasia of proximal bronchi. Fibreoptic bronchoscopy revealed no impacted mucus
      in the bronchi. BAL fluid from the right upper lobe yielded an increased total
      cell count with a high percentage of eosinophils. A transbronchial lung biopsy
      specimen showed a bronchoalveolar chronic inflammatory infiltrate composed of
      eosinophils, lymphocytes and plasma cells, associated with fibrosis of the
      alveolar walls. S. commune was identified in lavage fluid. Antibodies to this
      organism were present in the serum, confirming that S. commune was the cause of
      chronic eosinophilic pneumonia. Inhaled corticosteroids without accompanying oral
      corticosteroids or antifungal agents decreased the respiratory symptoms, and the
      infiltrates disappeared from the chest radiograph within a few days

PMID- 14708556
TI  - Antineutrophil cytoplasmic antibody positive alveolar haemorrhage during
      propylthiouracil therapy for hyperthyroidism.
AB  - Recently, propylthiouracil (PTU) has been thought to be one of the possible
      causes of antineutrophil cytoplasmic antibody (ANCA)-associated small vessel
      vasculitis syndrome, resulting in glomerulonephritis and, infrequently, diffuse
      alveolar haemorrhage (DAH). The mechanism of ANCA-positive vasculitis during PTU
      therapy is still unknown. Herein, we describe the case of a 59-year-old woman who
      developed myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA positive DAH,
      without any other organ system involvement, during PTU therapy. Diminution and
      discontinuation of PTU resulted in a positive response. To our knowledge, this is
      the first documentation of both MPO- and PR3-ANCA-positive DAH, without systemic
      manifestations, developing during PTU therapy.

PMID- 14708557
TI  - Pulmonary strongyloidiasis presenting as chronic bronchitis leading to
      interlobular septal fibrosis and cured by treatment.
AB  - Two patients presented with long-standing chronic bronchitis and exertional
      dyspnoea of 5 and 3 months' duration, respectively, and had interlobular septal
      fibrosis on chest high resolution CT. In the past both had lived in areas in
      which Strongyloides stercoralis was known to be endemic. Serological tests
      confirmed the diagnosis of pulmonary strongyloidiasis, and both patients were
      treated with anti-helminthic medications, including albendazole and ivermectin.
      Following this there was complete resolution of both symptomatic and radiological
      manifestations of their disease. An awareness of the possibility of Strongyloides
      infection presenting with respiratory symptoms in patients exposed to this
      parasite is important in the management of such patients.

PMID- 14708558
TI  - 'Iron lung': distinctive bronchoscopic features of acute iron tablet aspiration.
AB  - Three confirmed cases of acute iron tablet-induced necrosis due to a fulminant
      chemical burn injury to the tracheobronchial tree as a result of accidental
      inhalation and/or aspiration of iron tablets are described. Although histological
      confirmation has been relied upon for diagnosis, the distinctive bronchoscopic
      features may allow prompt recognition and treatment by bronchoscopists to prevent
      this potentially fatal condition.

PMID- 14708559
TI  - Extrapulmonary presentation of asymptomatic pulmonary lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare parenchymal lung disease, which affects
      young women of childbearing age and is characterized pathologically by
      proliferation of interstitial smooth muscle and formation of cysts in the lung.
      While LAM is usually predominantly a respiratory disorder, it can also initially
      involve other extrapulmonary organs. We report the case of a 35-year-old Chinese
      woman, who presented with a 4-week history of left thigh swelling which was found
      to be secondary to compression of pelvic veins by a mass lesion. The latter was
      found histologically to show LAM. Despite the patient being asymptomatic and
      displaying normal lung function, a thoracic high resolution CT scan showed
      typical features of early LAM. This case further illustrates that LAM can have
      multisystem involvement, and demonstrates the importance of being aware of the
      diagnosis in cases presenting with extrapulmonary manifestation, in order that
      patients are diagnosed and managed appropriately.

PMID- 14708560
TI  - Notice of duplicate publication.

PMID- 14708561
TI  - Suctioning tracheostomies is a skill worth learning.

PMID- 14708562
TI  - Abstracts of the 33rd Critical Care Congress. Orlando, Florida, USA. February 20
      25, 2004.

PMID- 14708563
TI  - Abstracts of the 55th Meeting of the German Society of Hygiene and Microbiology.
      28 September-1 October 2003, Dresden.

PMID- 14708564
TI  - [Proceedings of the 77th Annual Meeting of the French Society of Surgical
      Orthopedics and Trauma].

PMID- 14708565
TI  - Abstracts of  EUROECHO, the 7th Annual Meeting of the European Association of
      Echocardiography. Barcelona, Spain, 3-6 December 2003.

PMID- 14708567
TI  - Health data management 2004 resource guide.

PMID- 14708566
TI  - Regional hypoxia and partial pressure of carbon dioxide gradients: what is the
      link?

PMID- 14708569
TI  - HSJ campaign. Fit for purpose? HSJ's mental health campaign.

PMID- 14708568
TI  - Lead in their pencils.

PMID- 14708571
TI  - Phylogeny of plastids based on cladistic analysis of gene loss inferred from
      complete plastid genome sequences.
AB  - Based on the recent hypothesis on the origin of eukaryotic phototrophs, red
      algae, green plants, and glaucophytes constitute the "primary photosynthetic
      eukaryotes" (whose plastids may have originated directly from a cyanobacterium
      like prokaryote via primary endosymbiosis), whereas the plastids of other
      lineages of eukaryotic phototrophs appear to be the result of secondary or
      tertiary endosymbiotic events (involving a phototrophic eukaryote and a host
      cell). Although phylogenetic analyses using multiple plastid genes from a wide
      range of eukaryotic lineages have been carried out, some of the major
      phylogenetic relationships of plastids remain ambiguous or conflict between
      different phylogenetic methods used for nucleotide or amino acid substitutions.
      Therefore, an alternative methodology to infer the plastid phylogeny is needed.
      Here, we carried out a cladistic analysis of the "loss of plastid genes" after
      primary endosymbiosis using complete plastid genome sequences from a wide range
      of eukaryotic phototrophs. Since it is extremely unlikely that plastid genes are
      regained during plastid evolution, we used the irreversible Camin-Sokal model for
      our cladistic analysis of the loss of plastid genes. The cladistic analysis of
      the 274 plastid protein-coding genes resolved the 20 operational taxonomic units
      representing a wide range of eukaryotic lineages (including three secondary
      plastid-containing groups) into two large monophyletic groups with high bootstrap
      values: one corresponded to the red lineage and the other consisted of a large
      clade composed of the green lineage (green plants and Euglena) and the basal
      glaucophyte plastid. Although the sister relationship between the green lineage
      and the Glaucophyta was not resolved in recent phylogenetic studies using amino
      acid substitutions from multiple plastid genes, it is consistent with the rbcL
      gene phylogeny and with a recent phylogenetic study using multiple nuclear genes.
      In addition, our analysis robustly resolved the conflicting/ambiguous
      phylogenetic positions of secondary plastids in previous phylogenetic studies:
      the Euglena plastid was sister to the chlorophycean (Chlamydomonas) lineage, and
      the secondary plastids from the diatom (Odontiella) and cryptophyte (Guillardia)
      were monophyletic within the red lineage.

PMID- 14708570
TI  - Horizontal gene transfer of "prototype" Nramp in bacteria.
AB  - Eukaryotic Nramp genes encode divalent metal ion permeases important for
      nutrition and resistance to microbial infection. Bacterial homologs encode proton
      dependent transporters of manganese (MntH), and other divalent metal ions.
      Bacterial MntH were classified in three homology groups (A, B, C) and MntH C
      further subdivided in Calpha, Cbeta, Cgamma. The proteins from C. tepidum (MntH
      B) and E. faecalis (MntH Cbeta1, 2), divergent in sequence and hydropathy
      profile, conferred increased metal sensitivity when expressed in E. coli,
      suggesting conservation of divalent metal transport function in MntH B and C.
      Several genomic evidence suggest horizontal gene transfer (HGT) of mntH C genes:
      (i) The enterobacteria Wigglesworthia mntH Cbeta gene is linked to an Asn t-RNA,
      and its sequence most conserved with Gram positive bacteria homologs; (ii) all
      the Cbeta genes identified in oral streptococcaceae are associated with different
      potentially mobile DNA elements; (iii) Lactococcus lactis and Burkholderia mallei
      genomes contain an mntH gene prematurely terminated and a novel full-length mntH
      C gene; (iv) remarkable sequence relatedness between the unicellular alga C.
      reinhardtii "prototype" Nramp and some MntH Calpha (e.g., Nostoc spp., Listeria
      spp.) suggests HGT between Eukarya and Bacteria. Other "prototype" Nramp genes
      (intronless, encoding proteins strongly conserved with MntH A and B proteins)
      identified in invertebrates represent a possible source for transfer of Nramp
      genes toward opportunistic bacteria. This study demonstrates complex evolution of
      MntH in Bacteria. It is proposed that "prototype" Nramp are ancestors of
      bacterial MntH C proteins, which could facilitate bacterial infection.

PMID- 14708572
TI  - Secondary structure and molecular evolution of the mitochondrial small subunit
      ribosomal RNA in Agaricales (Euagarics clade, Homobasidiomycota).
AB  - The complete sequences and secondary structures of the mitochondrial small
      subunit (SSU) ribosomal RNAs of both mostly cultivated mushrooms Agaricus
      bisporus (1930 nt) and Lentinula edodes (2164 nt) were achieved. These secondary
      structures and that of Schizophyllum commune (1872 nt) were compared to that
      previously established for Agrocybe aegerita. The four structures are near the
      model established for Archae, Bacteria, plastids, and mitochondria; particularly
      the helices 23 and 37, described as specific to bacteria, are present. Within the
      four Agaricales (Homobasidiomycota), the SSU-rRNA "core" is conserved in size
      (966 to 1009 nt) with the exception of an unusual extension of 40 nt in the H17
      helix of S. commune. The four core sequences possess 76% of conserved positions
      and a cluster of C in their 3' end, which could constitute a signal involved in
      the RNA maturation process. Among the nine putative variable domains, three (V3,
      V5, V7) do not show significant length variations and possess similar percentages
      of conserved positions (69%) than the core. The other six variable domains show
      important length variations, due to independent large size inserted/deleted
      sequences, and higher rates of nucleotide substitutions than the core (only 31%
      of conserved positions between the four species). Interestingly, the
      inserted/deleted sequences are located in few preferential sites (hot spots for
      insertion/deletion) where they seem to arise or disappear haphazardly during
      evolution. These sites are located on the surface of the tertiary structure of
      the 30S ribosomal subunit, at the beginning of hairpin loops; the insertions lead
      to a lengthening of existing hairpins or to branching loops bearing up to five
      additional helices.

PMID- 14708573
TI  - The peroxidase gene family in plants: a phylogenetic overview.
AB  - The 73 class III peroxidase genes in Arabidopsis thaliana were used for surveying
      the evolutionary relationships among peroxidases in the plant kingdom. In
      Arabidopsis, the 73 genes were clustered in robust similarity groups. Comparison
      to peroxidases from other angiosperms showed that the diversity observed in
      Arabidopsis preceded the radiation of dicots, whereas some clusters were absent
      from grasses. Grasses contained some unique peroxidase clusters not seen in dicot
      plants. We found peroxidases in other major groups of land plants but not in
      algae. This might indicate that the class III peroxidase gene family appeared
      with the colonization of land by plants. The present survey may be used as a
      rational basis for further investigating the functional roles of class III
      peroxidases.

PMID- 14708575
TI  - The phylogenetic history of the MHC class I gene families in pig, including a
      fossil gene predating mammalian radiation.
AB  - More than 990 kb of the 1200 kb in the SLA class I region of the pig major
      histocompatibility complex (MHC) have been sequenced. The present study was
      designed to establish the evolution of this region which was best understood by
      distinguishing three periods. The most recent period, which extended from 40 to
      15 mya, probably corresponded to five rounds of duplication of a basic unit. This
      unit consisted of a single class I gene linked to widely dispersed repeats, and
      one SLA-specific repeat motif. The duplications gave rise to six SLA classical
      class I genes. The second evolutionary period corresponded to the emergence of
      the SLA nonclassical class I genes, i.e. after the suidae separated from the
      other artiodactyl species about 65 mya. The third period appeared to correspond
      to a much more remote age when the ancestor of the gene SLA-11 existed.
      Comparative studies of the human and pig sequences of the class I-containing
      segments indeed revealed the presence within the human HSR1-ZNF segment of relics
      of a human class I fossil gene which appeared to be orthologous to the 5' moiety
      of the SLA-11 pseudogene. This was the first evidence that a class I gene existed
      in this location at least 110-120 mya in the MHC class I region of the precursor
      of the mammalian species. Human/pig sequence comparison also revealed that the
      presumably functional pig MIC2 gene was probably orthologous to the human
      functional MICA or MICB genes.

PMID- 14708574
TI  - Phylogenetic analysis of eukaryotes using heat-shock protein Hsp90.
AB  - Most eukaryote molecular phylogenies have been based on small-subunit ribosomal
      RNA as its database includes the most species, but serious problems have been
      encountered that can make these trees misleading. More recent studies using
      concatenated protein sequences have increased the data per organism, reducing
      misleading signals from a single sequence, but taxon sampling is limited. To
      increase the database of protein-coding genes we sequenced the cytosolic form of
      heat-shock protein Hsp90 from a broad variety of previously unsampled eukaryote
      groups: protozoan flagellates (phyla Choanozoa, Apusozoa, Cercozoa) and all three
      groups of chromists (Cryptophyta, Heterokonta, Haptophyta). Gamma-corrected
      distance trees robustly show three groups: bacterial sequences are sister to all
      eukaryote sequences, which are cleanly subdivided into the cytosolic sequences
      and a clade comprising the chloroplast and endoplasmic reticulum (ER) Hsp90
      sequences. The eukaryote cytosolic sequences comprise a robust opisthokont clade
      (animals/Choanozoa/fungi), a bikont clade, and an amoebozoan branch. However
      their topology is not robust. When the cytosolic sequences are rooted using only
      the ER/ chloroplast clade as outgroup the amoebozoan Dictyostelium is sister to
      the opisthokonts forming a unikont clade in the distance tree. Congruence of this
      tree with that for concatenated mitochondrial proteins suggests that the root of
      the eukaryote tree is between unikonts and bikonts. Gamma-corrected maximum
      likelihood analyses of cytosolic sequences alone (519 unambiguously aligned amino
      acid positions) show bikonts as a clade, as do least-squares distance trees, but
      with other distance methods and parsimony the sole amoebozoan species branches
      weakly within bikonts. Choanozoa are clearly sisters to animals. Some major
      bikont groups (e.g. green plants, alveolates, Euglenozoa) are consistently
      recovered, but others (e.g. discicristates, chromalveolates) appear only in some
      trees; the backbone of the bikont subtree is not resolved, the position of groups
      represented only by single sequences being particularly unclear. Although single
      gene trees will probably never resolve these uncertainties, the congruence of
      Hsp90 trees with other data is greater than for most other molecules and further
      taxon sampling of this molecule is recommended.

PMID- 14708576
TI  - The evolution of tRNA-Leu genes in animal mitochondrial genomes.
AB  - Animal mitochondrial genomes usually have two transfer RNAs for leucine: one,
      with anticodon UAG, translates the four-codon family CUN, while the other, with
      anticodon UAA, translates the two-codon family UUR. These two genes must differ
      at the third anticodon position, but in some species the genes differ at many
      additional sites, indicating that these genes have been independent for a long
      time. Duplication and deletion of genes in mitochondrial genomes occur frequently
      during the evolution of the Metazoa. If a tRNA-Leu gene were duplicated and a
      substitution occurred in the anticodon, this would effectively turn one type of
      tRNA into the other. The original copy of the second tRNA type might then be lost
      by a deletion elsewhere in the genome. There are several groups of species in
      which the two tRNA-Leu genes occur next to one another (or very close) on the
      genome, which suggests that tandem duplication has occurred. Here we use RNA
      specific phylogenetic methods to determine evolutionary trees for both genes. We
      present evidence that the process of duplication, anticodon mutation, and
      deletion of tRNA-Leu genes has occurred at least five times during the evolution
      of the metazoa-once in the common ancestor of all protostomes, once in the common
      ancestor of echinoderms and hemichordates, once in the hermit crab, and twice
      independently in mollusks.

PMID- 14708577
TI  - Isolation of a neurotoxin (alpha-colubritoxin) from a nonvenomous colubrid:
      evidence for early origin of venom in snakes.
AB  - The evolution of venom in advanced snakes has been a focus of long-standing
      interest. Here we provide the first complete amino acid sequence of a colubrid
      toxin, which we have called alpha-colubritoxin, isolated from the Asian ratsnake
      Coelognathus radiatus (formerly known as Elaphe radiata), an archetypal
      nonvenomous snake as sold in pet stores. This potent postsynaptic neurotoxin
      displays readily reversible, competitive antagonism at the nicotinic receptor.
      The toxin is homologous with, and phylogenetically rooted within, the three
      finger toxins, previously thought unique to elapids, suggesting that this toxin
      family was recruited into the chemical arsenal of advanced snakes early in their
      evolutionary history. LC-MS analysis of venoms from most other advanced snake
      lineages revealed the widespread presence of components of the same molecular
      weight class, suggesting the ubiquity of three-finger toxins across advanced
      snakes, with the exclusion of Viperidae. These results support the role of venom
      as a key evolutionary innovation in the early diversification of advanced snakes
      and provide evidence that forces a fundamental rethink of the very concept of
      nonvenomous snake.

PMID- 14708578
TI  - A survey of codon and amino acid frequency bias in microbial genomes focusing on
      translational efficiency.
AB  - Unequal use of synonymous codons has been found in several prokaryotic and
      eukaryotic genomes. This bias has been associated with translational efficiency.
      The prevalence of this bias across lineages is currently unknown. Here, a new
      method (GCB) to measure codon usage bias is presented. It uses an iterative
      approach for the determination of codon scores and allows the computation of an
      index of codon bias suitable for interspecies comparison. A server to calculate
      GCB-values of individual genes as well as a list of compiled results are
      available at www.g21.bio.uni-goettingen.de. The method was applied to complete
      bacterial genomes. The relation of codon usage bias with amino acid composition
      and the choice of stop codons were determined and discussed.

PMID- 14708580
TI  - MgtC as a horizontally-acquired virulence factor of intracellular bacterial
      pathogens: evidence from molecular phylogeny and comparative genomics.
AB  - MgtC is a virulence factor required for intramacrophage survival and growth in
      low Mg2+ medium in two pathogens that are not phylogenetically related,
      Salmonella typhimurium and Mycobacterium tuberculosis. In S. typhimurium, mgtC is
      carried by the SPI-3 pathogenicity island and hybridization studies have
      suggested that the distribution of mgtC among enterobacteria is limited. In the
      present study, we searched for the presence of mgtC-like sequences in eubacterial
      genomes. Analyses of MgtC-like proteins phylogeny and mgtC-like chromosomal
      context support the hypothesis that mgtC has been acquired by horizontal gene
      transfer repeatedly throughout bacterial evolution. In addition, the phylogenetic
      analysis revealed the existence of a subgroup of proteins, that includes the S.
      typhimurium and M. tuberculosis MgtC proteins, as well as MgtC-related proteins
      from other pathogens that are able to survive in macrophages, B. melitensis and
      Y. pestis. We propose that MgtC has a similar function in all these distantly
      related pathogens, most likely providing the ability to grow in a low Mg2+
      environment.

PMID- 14708579
TI  - Are radical and conservative substitution rates useful statistics in molecular
      evolution?
AB  - A DNA mutation in a protein coding gene which causes an amino acid change can be
      classified as "conservative" or "radical" depending on the magnitude of the
      physicochemical difference between the two amino acids: radical mutations involve
      larger changes than conservative mutations. Here, I examine two key issues in
      determining whether radical and conservative substitution rates are useful
      statistics in molecular evolution. The first issue is whether such rates can be
      estimated reliably, and for this purpose I demonstrate considerable improvements
      achieved by simple modifications to an existing method. The second issue is
      whether conservative and radical substitution rates can tell us something about
      selection on protein function. I address this problem by estimating positive and
      negative selection on conservative and radical mutations using polymorphism and
      divergence data from Drosophila. These analyses show that negative selection, but
      not positive selection, differs significantly between conservative and radical
      mutations. The power of conservative and radical substitution rates in testing
      the nearly neutral theory of molecular evolution is illustrated by the analysis
      of two mammalian datasets.

PMID- 14708581
TI  - Look before you leap.

PMID- 14708582
TI  - Nailing the interview.

PMID- 14708583
TI  - Tracking travel trends.

PMID- 14708584
TI  - Advice from the trenches.

PMID- 14708585
TI  - Confessions of an account manager.

PMID- 14708586
TI  - Activation of B-raf in non-malignant nevi predicts a novel tumor suppressor gene
      in melanoma (MAP kinase phosphatase).

PMID- 14708587
TI  - The continuing saga of epidermal stem cells.

PMID- 14708588
TI  - Decreased serum ferritin and alopecia in women.

PMID- 14708589
TI  - Matrix metalloproteinase-19: what role does this enzyme play in wound healing?

PMID- 14708590
TI  - Fibrin is a many splendored thing.

PMID- 14708591
TI  - Talk to the hand 'cause the nucleus ain't listening: adhesion, communication, and
      tumor cell invasion in the skin.

PMID- 14708592
TI  - The molecular basis of lymphocyte recruitment to the skin: clues for pathogenesis
      and selective therapies of inflammatory disorders.
AB  - Spatial compartmentalization and tissue-selective localization of T lymphocytes
      to the skin are crucial for immune surveillance and the pathogenesis of various
      disorders including common inflammatory diseases such as atopic dermatitis or
      psoriasis, but also malignancies such as cutaneous T cell lymphomas. Cutaneous
      recruitment of lymphocytes is a highly complex process that involves
      extravasation, migration through the dermal connective tissue, and eventually,
      localization to the epidermis. An intertwined network of cytokines and chemokines
      provides the road signs for leukocyte migration, while various adhesion receptors
      orchestrate the dynamic events of cell-cell and cell-substrate interactions
      resulting in cutaneous localization of T cells. Selectively targeting the
      functions of molecules involved in this interplay promises exciting new
      therapeutic options for treating inflammatory skin disorders.

PMID- 14708593
TI  - Keratin 15 promoter targets putative epithelial stem cells in the hair follicle
      bulge.
AB  - Putative epithelial stem cells in the hair follicle bulge are thought to play
      pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous
      epithelium. Elucidating the role of bulge cells in these processes has been
      hampered by the lack of gene promoters that target this area with specificity.
      Here we describe the isolation of the mouse keratin 15 (K15) promoter and
      demonstrate its utility for preferentially targeting hair follicle bulge cells in
      adult K15/lacZ transgenic mice. We found that patterns of K15 expression and
      promoter activity changed with age and correlated with levels of differentiation
      within the cutaneous epithelium; less differentiated keratinocytes in the
      epidermis of the neonatal mouse and in the bulge area of the adult mouse
      preferentially expressed K15. These findings demonstrate the utility of the K15
      promoter for targeting epithelial stem cells in the hair follicle bulge and set
      the stage for elucidating the role of bulge cells in skin biology.

PMID- 14708594
TI  - Profile of transforming growth factor-beta responses during the murine hair
      cycle.
AB  - Transforming growth factor-beta (TGF-beta) appears to promote the regression
      phase of the mammalian hair cycle, in vivo in mice and in organ culture of human
      hair follicles. To assess the relationship between TGF-beta activity and
      apoptosis of epithelial cells during the murine hair cycle, we identified active
      TGF-beta responses using phospho-Smad2/3-specific antibodies (PS2). Strong,
      nuclear PS2 staining was observed in the outer root sheath throughout the anagen
      growth phase. Some bulb matrix cells were positive for PS2 during late anagen.
      Extensive, but weak, staining was observed in this region at the anagen-catagen
      transition. We also examined expression of TGF-beta-stimulated clone-22 (TSC-22),
      which is associated with TGF-beta-induced apoptosis of some cell lines.
      Recombinant rat TSC-22 was used to generate a rabbit anti-TSC-22 antibody useful
      for immunohistochemistry. TSC-22 RNA accumulation and immunoreactivity were
      observed in follicles throughout the murine hair cycle, including the dermal
      papilla and lower epithelial strand of late-catagen hair follicles. Neither the
      expression pattern nor the presence of nuclear TSC-22 correlated with the sites
      of apoptosis, suggesting that TSC-22 is not an effector of apoptosis in mouse
      catagen hair follicles. These studies support a complex role for TGF-beta in
      regulating the regression phase of the cycle, with potential for indirect
      promotion of apoptosis during the anagen-catagen transition.

PMID- 14708595
TI  - Kit is expressed by epithelial cells in vivo.
AB  - In mammalian skin, stem cell factor (SCF) regulates the proliferation and
      maturation of mast cells and melanocytes, which are thought to be the only
      cutaneous cells that express the Kit-tyrosine kinase receptor (Kit) and respond
      to epithelial and mesenchymal-derived SCF. We previously had noted, however, the
      presence of Kit+ cells in murine hair follicles, in an introepithelial tissue
      compartment devoid of melanocytes and mast cells. Here we have identified the
      nature of this Kit+ population of cells in hair follicles of C57BL/6 mice. Anagen
      hair follicles showed strong Kit immunoreactivity not only in the pigmentary unit
      above the follicular dermal papilla but also in a much more proximally located,
      homogenous group of nondendritic, nonmelanized cells. By immunohistochemistry
      (desmoplakin+/Trp-1-) and electron microscopy (presence of tonofilaments,
      desmosomes, lack of melanosomes), these Kit+ cells were shown to be hair matrix
      keratinocytes and were also found in melanocyte-deficient hair follicles
      (Kit(Sl)/Kit(Sl-d) mice, Kit-neutralizing antibody-treated C57BL/6 mice).
      Expression of Kit and SCF was strongly hair-cycle-dependent, suggesting a
      functional role of epithelial Kit expression in hair growth control. This was
      supported by the observation that mice unable to respond to SCF stimulation
      (Kit(W)/Kit(W-v)) showed a significant retardation of anagen development compared
      to their wild-type littermates. The expression of Kit in the most rapidly
      proliferating compartment of the hair follicle epithelium suggests intriguing, as
      yet unexplored new functions of Kit signaling in epithelial cell biology.

PMID- 14708596
TI  - Decreased serum ferritin is associated with alopecia in women.
AB  - Alopecia in women is a common problem, and conflicting observational data have
      failed to determine whether an association exists between alopecia and iron
      deficiency in women. We therefore utilized an analytical cross-sectional
      methodology to evaluate whether common types of alopecia in women are associated
      with decreased tissue iron stores, as measured by serum ferritin. We studied
      patients with telogen effluvium (n = 30), androgenetic alopecia (n = 52),
      alopecia areata (n = 17), and alopecia areata totalis/universalis (n = 7). The
      normal group consisted of 11 subjects without hair loss from the same referral
      base and source population as those patients with alopecia. We analyzed the data
      utilizing the unpaired Student's t test assuming unequal variances with an alpha
      adjustment for multiple comparisons to assess whether the mean ages, ferritin
      levels, and hemoglobin levels of women without hair loss differed from the means
      in each alopecia group. The mean age of patients and normals did not differ
      significantly. We found that the mean ferritin level (ng per ml [95% confidence
      intervals]) in patients with androgenetic alopecia (37.3 128.4, 46.1]) and
      alopecia areata (24.9 [17.2, 32.6]) were statistically significantly lower than
      in normals without hair loss (59.5 [40.8, 78.1]). The mean ferritin levels in
      patients with telogen effluvium (50.1 [33.9, 66.33]) and alopecia areata
      totalis/universalis (52.3 [23.1, 81.5]) were not significantly lower than in
      normals. Our findings have implications regarding therapeutics, clinical trial
      design, and understanding the triggers for alopecia.

PMID- 14708597
TI  - Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation
      by epidermal proliferation.
AB  - Most of the matrix metalloproteinases (MMP) are not expressed in normal intact
      skin but they are upregulated in inflamed or diseased skin. The recently cloned
      MMP-19 is one of the few MMP members that are also expressed in healthy
      epidermis. In this study, we found that MMP-19 is generally coexpressed with
      cytokeratin 14 that is confined to keratinocytes of the stratum basale. MMP-19
      was also detected in hair follicles, sebaceous glands, and eccrine sweat glands.
      Its expression, however, changed in cutaneous diseases exhibiting increased
      alternations of epidermal proliferation, such as psoriasis, eczema, and tinea. In
      the affected area, MMP-19 was also found in suprabasal and spinous epidermal
      layers. We also studied the regulation of MMP-19 expression at the protein level,
      as well as by using a promoter assay. The constitutive expression of MMP-19 was
      upregulated with phorbol myristate acetate and downregulated with retinoic acid
      and dexamethasone. Tumor necrosis factor-alpha, interleukin (IL)-6, TGF-beta, IL
      15, IL-8, and RANTES as well as the bacterial compounds lipopolysaccharide and
      lipoteichoic acid did not show any profound effect in HaCaT cells. In contrast,
      type IV and type I collagens upregulated MMP-19 significantly. The dysregulation
      of MMP-19 expression in epidermis suggests its possible involvement in the
      perpetuation of cutaneous infections and proliferative disorders such as
      psoriasis.

PMID- 14708598
TI  - Matrix metalloproteinase-19 expression in dermal wounds and by fibroblasts in
      culture.
AB  - Here, we have examined the expression of matrix metalloproteinase-19 (MMP-19) in
      human cutaneous wounds and by human skin fibroblasts in culture. Expression of
      MMP-19 was detected by immunohistochemistry in fibroblasts, capillary endothelial
      cells, and macrophages in the dermal layer of large granulating wounds, as well
      as in chronic venous and decubitus ulcers. MMP-19 mRNA expression and pro-MMP-19
      production by dermal fibroblasts in culture was potently enhanced by tumor
      necrosis factor-alpha (TNF-alpha). Induction of MMP-19 expression by TNF-alpha
      was prevented partially by blocking the activation of extracellular signal
      regulated kinase (ERK)-1/2 by PD98059 and p38 activity by SB203580. Activation of
      ERK1/2 by adenovirus-mediated delivery of constitutively active MAPK/ERK kinase 1
      resulted in the induction of MMP-19 expression. Activation of p38 alone by
      adenovirally delivered constitutively active MAPK kinase 3b (MKK3b) and MKK6b
      also enhanced MMP-19 production, and the most potent induction of MMP-19
      expression was noted when ERK1/2 was activated in combination with p38.
      Activation of c-Jun N-terminal kinase (NK). Abundant pro-MMP-19 production by
      fibroblasts was associated with proteolytic processing of secreted pro-MMP-19.
      These results suggest a role of MMP-19 in cutaneous wound repair and identify
      three distinct signaling pathways, which coordinately mediate induction of MMP-19
      expression in fibroblasts: mitogen-activated ERK1/2 pathway and stress-activated
      JNK and p38 pathways, of which control proteolytic activity of dermal
      fibroblasts.

PMID- 14708599
TI  - Mechanisms of hypoxic regulation of plasminogen activator inhibitor-1 gene
      expression in keloid fibroblasts.
AB  - Keloids are an excessive accumulation of extracellular matrix. Although numerous
      studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in
      keloid fibroblasts compared with those of normal skin. Their specific mechanisms
      involved in the differential expression of PAI-1 in these cell types. In this
      study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and
      their derived dermal fibroblasts, attesting to the persistence, if any, of
      fundamental differences between in vivo and in vitro paradigms. We further
      examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in
      dermal fibroblast derived from keloid lesions and associated clinically normal
      peripheral skins from the same patient. Primary cultures were exposed to an
      environmental hypoxia or desferroxamine. We found that the hypoxia-induced
      elevation of PAI-1 gene appears to be regulated at both transcriptional and post
      transcriptional levels in keloid fibroblasts. Furthermore, our results showed a
      consistent elevation of HIF-1alpha protein level in keloid tissues compared with
      their normal peripheral skin controls, implying a potential role as a biomarker
      for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia
      inducible factor 1alpha (HIF-1alpha) led to the downregulation of steady-state
      levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our
      results suggest that HIF-1alpha may be a novel therapeutic target to modulate the
      scar fibrosis process.

PMID- 14708600
TI  - Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: unusual
      phenotypic alterations in Scandinavian patients with epidermolytic
      hyperkeratosis.
AB  - Epidermolytic hyperkeratosis is a rare autosomal dominant inherited skin disorder
      caused by keratin 1 or keratin 10 mutations. Keratins are major structural
      proteins of the epidermis, and in keratinocytes committed to terminal
      differentiation the intermediate filaments are composed of keratin 1 and keratin
      10 heterodimers. The majority of reported mutations (86.6%) are heterozygous
      single point mutations and most of these are located in the 1A and 2B regions of
      the highly conserved keratin alpha-helical rod domain. We have studied eight
      Scandinavian families with epidermolytic hyperkeratosis and identified three
      point mutations, two codon deletions, two splice site mutations, and a complex
      deletion/insertion. Two of the point mutations were in the KRT1 gene (F191C and
      K177N) and the other was in KRT10 (L453P). All three patients had associated
      palmoplantar keratoderma. The splice site mutations in KRT1 both caused a large
      deletion removing 22 codons (delta176-197) from the 1A helical domain. Codon
      deletions were found in KRT1 (delta170-173) and in KRT10 (delta161-162) in two
      patients with a severe phenotype. A final patient had a more complex mutation
      with a large deletion (442 bp) together with a large insertion (214 bp) of
      unknown origin that caused deletion of exon 6 in KRT1. In conclusion, we have
      found eight novel keratin mutations that cause epidermolytic hyperkeratosis with
      differing phenotypes. Even when a large part of keratin 1 (46 amino acids) is
      deleted, surprisingly mild phenotypes can result, suggesting that genotype
      phenotype relationships in epidermolytic hyperkeratosis are complex and do not
      solely depend on the type of mutation but also depend on interactions between the
      behavior of the mutant protein and the cellular environment.

PMID- 14708601
TI  - Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can
      produce type VII collagen at the basement membrane zone.
AB  - Type VII collagen is synthesized and secreted by both human keratinocytes and
      fibroblasts. Although both cell types can secrete type VII collagen, it is
      thought that keratinocytes account for type VII collagen at the dermal-epidermal
      junction (DEJ). In this study, we examined if type VII collagen secreted solely
      by dermal fibroblasts could be transported to the DEJ. We established
      organotypic, skin-equivalent cultures composed of keratinocytes from patients
      with recessive dystrophic epidermolysis bullosa (RDEB) and normal dermal
      fibroblasts. Immuno-labeling of skin equivalent sections with the anti-type VII
      collagen antibody revealed tight linear staining at the DEJ. RDEB fibroblasts,
      were gene-corrected to make type VII collagen and used to regenerate human skin
      on immune-deficient mice. The human skin generated by gene-corrected RDEB
      fibroblasts or normal human fibroblasts combined with RDEB keratinocytes restored
      type VII collagen expression at the DEJ in vivo. Further, intradermal injection
      of normal human or gene-corrected RDEB fibroblasts into mouse skin resulted in
      the stable expression of human type VII collagen at the mouse DEJ. These data
      demonstrate that human dermal fibroblasts alone are capable of producing type VII
      collagen at the DEJ, and it is possible to restore type VII collagen gene
      expression in RDEB skin in vivo by direct intradermal injection of fibroblasts.

PMID- 14708602
TI  - Truncation of CGI-58 protein causes malformation of lamellar granules resulting
      in ichthyosis in Dorfman-Chanarin syndrome.
AB  - Dorfman-Chanarin syndrome is a rare autosomal recessive inherited lipid storage
      disease characterized by ichthyosis, leukocyte lipid vacuoles, and involvement of
      several internal organs. Recently, CGI-58 mutations were identified as the cause
      of Dorfman-Chanarin syndrome. The physiologic roles of the CGI-58 protein and the
      pathomechanisms of Dorfman-Chanarin syndrome still remain to be clarified,
      however. The patient, a 16-y-old male, demonstrated ichthyosis, small ears, lipid
      vacuoles in his leukocytes, liver dysfunction, and mental retardation. Sequencing
      of CGI-58 revealed that the patient was homozygous for a novel nonsense mutation
      R184X, in exon 4. The putative truncated protein was 52.4% of the length of the
      normal CGI-58 polypeptide and lacked approximately 60% of the lipid binding
      region, 66.4% of the alpha/beta hydrolase folding segment of the polypeptide, and
      two of the CGI-58 catalytic triads, resulting in a significant loss of
      lipase/esterase/thioesterase activity. Electron microscopy revealed a large
      number of abnormal lamellar granules, a disturbed intercellular lamellar
      structure, and lipid vacuoles in the epidermis. These results suggested that CGI
      58 protein is involved in the lipid metabolism of lamellar granules and that
      defective lipid production in lamellar granules caused by a CGI-58 protein
      deficiency is involved in the pathogenesis of ichthyosis in Dorfman-Chanarin
      syndrome.

PMID- 14708603
TI  - Clouston syndrome can mimic pachyonychia congenita.
AB  - We studied three families suffering from nail abnormalities who had previously
      been diagnosed as pachyonychia congenita. No keratin gene mutations were
      detected. Sequencing of connexin 30 (GJB6 gene) in these patients identified
      heterozygous missense mutations G11R and A88V that are known to be associated
      with Clouston syndrome. This unexpected finding expands the Clouston syndrome
      phenotype and suggests that some patients diagnosed with pachyonychia may in fact
      be suffering from Clouston syndrome.

PMID- 14708604
TI  - Thiol antioxidants block the activation of antigen-presenting cells by contact
      sensitizers.
AB  - Strong contact sensitizers are able to induce signal transduction mechanisms such
      as tyrosine phosphorylation and activation of MAP kinases in antigen-presenting
      cells. We studied the capacity of different antioxidants (ascorbic acid, alpha
      tocopherol, pyrrolidine dithiocarbamate, N-acetylcysteine, and glutathione) to
      block the increase in tyrosine phosphorylation in human monocytes seen after
      stimulation with strong contact sensitizers. Human peripheral blood mononuclear
      cells were stimulated with 5-chloro-2-methylisothiazolinone plus 2
      methylisothiazolinone in the presence or absence of these antioxidants. The total
      amount of membrane-associated phosphotyrosine in CD14+ cells was quantified using
      flow cytometric techniques. Complete inhibition of tyrosine phosphorylation was
      noticed when cells were stimulated in the presence of N-acetylcysteine or
      glutathione. Using N-acetylcysteine as inhibitor similar results were obtained
      for cells stimulated with formaldehyde, thimerosal methyldibromoglutaronitrile,
      diphenylcyclopropenone, p-phenylenediamine, toluene-2,5-diamine, and 2,4
      dinitrofluorobenzene. By use of a trinitrophenyl-specific monoclonal antibody it
      was shown that N-acetylcysteine as well as cysteine prevents the binding of 2,4,6
      trinitrochlorobenzene to proteins in monocytes and monocyte-derived mature
      dendritic cells. Furthermore, the capacity of N-acetylcysteine to block the
      activation of p38 and ERK1/2 MAP kinases by 2,4,6-trinitrochlorobenzene was
      demonstrated. The radical scavengers ascorbic acid and alpha-tocopherol as well
      as the nuclear factor kappaB inhibitor pyrrolidine dithiocarbamate failed to
      prevent the increase in tyrosine phosphorylation. Our data present evidence that
      reactive oxygen species as well as transcription factor nuclear factor kappaB
      seem to be unimportant for the induction of tyrosine phosphorylation by contact
      sensitizers. On the other hand, protection of thiol groups using compounds with
      free sulfhydryl groups is very effective to block this process. This finding may
      have implications for prevention of occupational sensitization to strong contact
      allergens.

PMID- 14708605
TI  - Chemokine receptor expression on neoplastic and reactive T cells in the skin at
      different stages of mycosis fungoides.
AB  - We analyzed the expression of 13 chemokine receptors in mycosis fungoides, in
      order to assess the contribution of chemotaxis to the pathogenesis of the
      disease. Material from skin biopsies of six patients with early disease and six
      patients at the tumor stage of mycosis fungoides was analyzed by
      immunohistochemistry and partly also by flow cytometry. The receptors CCR1, CCR2,
      CCR3, CCR5, CCR6, CXCR1, CXCR2, CXCR5, and CX3CR1 were rarely and inconsistently
      detected in lesional skin and thus their participation in mycosis fungoides could
      largely be ruled out. In contrast, CCR4, CXCR3, and CXCR4 were substantially
      expressed on both mycosis fungoides cells and the surrounding reactive T cells in
      the early patch and plaque stages of the disease, indicating an involvement of
      these chemokine receptors in the disease process. In the tumor stage of mycosis
      fungoides, we interestingly observed a loss of a relevant chemokine receptor in
      four out of six patients. In three patients CXCR3 and in one patient CCR4 was
      absent on tumor mycosis fungoides cells, whereas the reactive T cells showed
      normal levels of expression. Within these samples, tumor mycosis fungoides cells
      exhibited high levels of CCR7, a chemokine receptor central for the entry of T
      cells to lymphatic tissue. Taken together, our data suggest that the loss of one
      or more of the chemokine receptors involved in the homing of the mycosis
      fungoides cells to the skin may trigger the latent potential of these cells to
      metastasize into regional lymphatic tissue.

PMID- 14708606
TI  - Sex differences in opioid-induced enhancement of contact hypersensitivity.
AB  - Previous research has demonstrated that, in male rats, the magnitude of contact
      hypersensitivity (CHS) can be enhanced by morphine treatment. The present
      experiments test the hypothesis that the mu-opioids morphine, etorphine, and
      buprenorphine would produce significant sex differences in the magnitude of 2,4
      dinitrofluorobenzene-induced CHS. During tests conducted over a 192-h period,
      morphine, etorphine, and buprenorphine administered before elicitation of CHS on
      the external surface of the ear (pinna) potentiated the CHS response, and the
      magnitude of this enhancement was significantly greater in females than males. By
      contrast, morphine had no effect on croton oil-induced irritant contact
      dermatitis, indicating that morphine's effects on CHS do not generalize to
      immunologically nonspecific forms of contact dermatitis. Activation of brain mu
      opioid receptors is responsible for the effects of morphine on CHS, because
      intracerebroventricular treatment with the mu-opioid receptor antagonist beta
      funaltrexamine blocked morphine potentiation of CHS in females and males. The sex
      differences in morphine potentiation of CHS appear to be a result of the gonadal
      hormonal milieu, because castration enhanced the CHS response following vehicle
      and morphine treatment, whereas ovariectomy significantly attenuated the
      enhancement of CHS by morphine. Because ovariectomy had no effect on the CHS
      response following vehicle treatment, the presence of female gonadal hormones may
      underlie the sex differences in morphine potentiation of CHS in gonadally intact
      animals. Overall, these results support an increased sensitivity to the
      modulatory effects of opioids on the CHS response in females that depends on the
      interaction between gonadal hormones and the central mu-opioid system.

PMID- 14708607
TI  - Thalidomide inhibits tumor necrosis factor-alpha production and antigen
      presentation by Langerhans cells.
AB  - Thalidomide is an effective treatment for several inflammatory and autoimmune
      disorders including erythema nodosum leprosum, Behcet's syndrome, discoid lupus
      erythematosus, and Crohn's disease. Thalidomide is believed to exert its anti
      inflammatory effects, at least in part, by inhibiting tumor necrosis factor-alpha
      (TNF-alpha) production by monocytes. We studied the effects of thalidomide on
      epidermal Langerhans cells (LC). LCs are epidermal antigen-presenting dendritic
      cells that play important roles in skin immune responses. Using the murine
      epidermis-derived dendritic cell lines, XS106A from A/J mice and XS52 from BALB/c
      mice as surrogates for LC, we found that thalidomide inhibited TNF-alpha
      production in a concentration-dependent manner. Northern blot analysis revealed
      that thalidomide significantly decreased the peak-induced mRNA level of TNF-alpha
      in XS106A cells and XS52 cells. We then examined the effect of thalidomide on
      fresh LC enriched to approximately 98% using positive selection of Ia+ cells with
      antibodies conjugated to magnetic microspheres. TNF-alpha production was reduced
      by 67.7% at a thalidomide concentration of 200 microg per mL. Thalidomide also
      had a profound inhibitory effect on the ability of LC to present antigen to a
      responsive TH1 clone. Thalidomide inhibits TNF-alpha production and the antigen
      presenting ability of epidermal LCs. These mechanisms may contribute to the
      therapeutic effects observed with this agent.

PMID- 14708608
TI  - Keratinocyte ATP release assay for testing skin-irritating potentials of
      structurally diverse chemicals.
AB  - Irritant dermatitis represents innate inflammatory responses to toxic chemicals.
      We have reported recently that ATP released from chemically injured keratinocytes
      may serve as a causative mediator for irritant dermatitis. In this study, we
      examined whether ATP release from keratinocytes would serve as a reliable readout
      for predicting skin irritating potentials of structurally diverse compounds. A
      vast majority (19/20) of the tested compounds, i.e., strong and weak irritant
      chemicals selected from the literature, induced rapid (<10 min) and significant
      (P<0.05) ATP release from Pam 212 keratinocytes. Two compounds caused no
      detectable skin inflammation in our standard mouse model, documenting relatively
      high sensitivity (false negative rate of 0/18) and specificity (false positive
      rate of 1/20) of our ATP release assay. Selected compounds, primarily those
      containing phenol residues or hydrophobic hydrocarbon chains, triggered rapid
      (<10 min) and robust leakage of a fluorescence probe from liposomes, suggesting
      that lipid bilayers serve as one, but not the only, target moiety on
      keratinocytes. Not only do our data support the pathogenic role for keratinocyte
      derived ATP in irritant dermatitis, they also form the basis for a formal
      validation study to evaluate the utility of the keratinocyte-based in vitro assay
      in screening environmental and industrial chemicals.

PMID- 14708609
TI  - H1 and H2 histamine receptors are absent on Langerhans cells and present on
      dermal dendritic cells.
AB  - Human monocyte-derived dendritic cells (MoDC) have both histamine H1 and H2
      receptors and can induce CD86 expression by histamine. Nevertheless, it has not
      been reported whether human epidermal Langerhans cells (LC) have histamine
      receptors or not. In this study, using RT-PCR, we investigated the expression of
      H1 and H2 receptor mRNA on DC with the features of LC (LC-like DC) that were
      generated in vitro from peripheral blood monocytes, LC derived from CD34+
      hematopoietic progenitor cells, and LC obtained from human epidermis. We compared
      the histamine-induced CD86 expression among these cells. In contrast to MoDC, LC
      and LC-like DC did not express H1 or H2 receptors. In addition, they could not
      augment the CD86 expression by histamine. Interestingly, when transforming growth
      factor-beta1 (TGF-beta1) was added to the culture of MoDC, the expression of H1
      and H2 receptors and the histamine-induced CD86 expression were abrogated in a
      concentration-dependent fashion. Finally, in the assessment of the cell surface
      expression of histamine receptors using fluorescence-labeled histamine, histamine
      could bind to MoDC and dermal dendritic cells obtained from the skin, whereas
      there was no specific binding of histamine to LC-like DC or LC obtained from the
      skin. These data suggest that LC do not express either H1 or H2 receptors, mainly
      because of the effect of TGF-beta1. This made a striking contrast with the
      expression of the functional H1 and H2 receptors on MoDC and dermal dendritic
      cells.

PMID- 14708610
TI  - Immune protection factors of chemical sunscreens measured in the local contact
      hypersensitivity model in humans.
AB  - We conducted a randomized trial designed to calculate human in vivo immune
      protection factors of two sunscreen preparations in a model of ultraviolet
      induced local suppression of the induction of contact hypersensitivity to 2,4
      dinitrochlorobenzene. Seventy-five male subjects were exposed in a multistage
      study to multiples of their individual minimal erythema dose of solar-simulated
      ultraviolet radiation with or without protection by an ultraviolet B sunscreen
      (sun protection factor 5.2) or a broad-spectrum ultraviolet A + B sunscreen (sun
      protection factor 6.2). After 24 h subjects were sensitized with 50 microL of
      0.0625% 2,4-dinitrochlorobenzene on a nonirradiated or ultraviolet-irradiated
      field on the buttock that was unprotected or protected by sunscreen. Three weeks
      after sensitization the subjects were challenged with varying concentrations of
      2,4-dinitrochlorobenzene on their upper inner arm, and the contact
      hypersensitivity response was determined at 48 and 72 h based on a
      semiquantitative clinical score, contact hypersensitivity lesion diameters, and
      dermal skin edema measurement by 20 MHz ultrasound. The 50% immunosuppressive
      dose ranged from 0.63 to 0.79 minimal erythema dose, depending on the endpoint
      parameter. Both sunscreens offered significant immunoprotection (p = 0.014-0.002)
      and their immune protection factor ranged from 4.5 to 5.8 (ultraviolet B
      sunscreen) and from 7.7 to 11 (ultraviolet A + B sunscreen). The immune
      protection factor of the ultraviolet B sunscreen was similar to the sun
      protection factor (5.2), whereas the sunscreen with broad-spectrum ultraviolet A
      + B protection exhibited better immunoprotective capacity than predicted from the
      sun protection factor.

PMID- 14708611
TI  - Inhibition of the epidermal growth factor receptor suppresses telomerase activity
      in HSC-1 human cutaneous squamous cell carcinoma cells.
AB  - Activation of telomerase, which stabilizes the telomere length of chromosomes, is
      crucial for the continued growth or progression of cancer cells. In a previous
      study, we showed that telomerase is frequently activated in skin tumors. Because
      epidermal growth factor plays an important role during the tumorigenesis of
      epithelial tissue, we have now examined the role of epidermal growth factor
      signaling in regulating telomerase activity using HSC-1 human cutaneous squamous
      cell carcinoma cells. Treatment of HSC-1 cells with AG 1478, an inhibitor of the
      epidermal growth factor receptor, or with a neutralizing antibody to the
      epidermal growth factor receptor, significantly suppressed their telomerase
      activity, in association with inhibiting their growth. The suppression of
      telomerase activity was obvious at day 3 and was maximal at day 5 after treatment
      with AG 1478. The suppression of telomerase activity correlated with the
      decreased expression of human telomerase catalytic subunit (hTERT) mRNA, the rate
      limiting determinant of its enzyme activity. The expression of c-Myc and of Sp1
      proteins, transcription factors for hTERT, were also suppressed by AG 1478 in HSC
      1 cells, but the expression of Ets-2 protein, another transcription factor, was
      not affected. The expression of Mad-1, a competitor of c-Myc, was increased.
      Inhibition of ERK, Src, or Akt suppressed telomerase activity in HSC-1 cells, but
      to a lesser extent than did treatment with AG 1478. Serum starvation suppressed
      telomerase activity, but addition of epidermal growth factor or transforming
      growth factor alpha did not increase it, indicating the involvement of other
      epidermal growth factor receptor ligands in the activation of telomerase in HSC-1
      cells. These data indicate that blockade of the epidermal growth factor receptor
      might be effective in inhibiting telomerase activity of squamous cell carcinomas,
      which would lead to the suppression of tumor growth.

PMID- 14708612
TI  - Side population keratinocytes resembling bone marrow side population stem cells
      are distinct from label-retaining keratinocyte stem cells.
AB  - Very primitive hematopoietic stem cells have been identified as side population
      cells based on their ability to efflux a fluorescent vital dye, Hoechst 33342. In
      this study we show that keratinocytes with the same side population phenotype are
      also present in the human epidermis. Although side population keratinocytes have
      the same dye-effluxing phenotype as bone marrow side population cells and can be
      blocked by verapamil, they do not express increased levels of the ABCG2
      transporter that is believed to be responsible for the bone marrow side
      population phenotype. Because bone marrow side population cells have stem cell
      characteristics, we sought to determine if side population keratinocytes
      represent a keratinocyte stem cell population by comparing side population
      keratinocytes with a traditional keratinocyte stem cell candidate, label
      retaining keratinocytes. Flow cytometric analyses demonstrated that side
      population keratinocytes have a different cell surface phenotype (low beta1
      integrin and low alpha6 integrin expression) than label-retaining keratinocytes
      and represent a unique population of keratinocytes distinctly different from the
      traditional keratinocyte stem cell candidate. Future in vivo studies will be
      required to analyze the function of side population keratinocytes in epidermal
      homeostasis and to determine if side population keratinocytes have
      characteristics of keratinocyte stem cells.

PMID- 14708613
TI  - Expression and localization of peroxisome proliferator-activated receptors and
      nuclear factor kappaB in normal and lesional psoriatic skin.
AB  - Abnormal epidermal proliferation and differentiation characterize the
      inflammatory skin disease psoriasis. Here we demonstrate that expression of
      PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that
      lipoxygenase products accumulating in psoriatic lesions are potent activators of
      PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly
      altered in lesional compared with nonlesional psoriatic skin. In the basal layer
      of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas
      p50, but not p65, localized to nuclei in the suprabasal layers, and this
      distribution was maintained in lesional psoriatic skin. In normal human
      keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of
      p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically
      interacts with the N-terminal Rel homology domain of p65. Irrespective of the
      presence of agonists none of the PPAR subtypes decreased p65-mediated
      transactivation in keratinocytes. In contrast p65, but not p50, was a potent
      repressor of PPAR-mediated transactivation. The p65-dependent repression of
      PPARdelta- but not PPARalpha- or PPARgamma-mediated transactivation was partially
      relieved by forced expression of the coactivators p300 or CBP. We suggest that
      deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated
      PPARdelta-mediated transactivation contributes to the pathologic phenotype of
      psoriasis.

PMID- 14708614
TI  - Lasers and microdermabrasion enhance and control topical delivery of vitamin C.
AB  - The objective of this study was to evaluate the ability of lasers and
      microdermabrasion, both of which are skin resurfacing modalities, to enhance and
      control the in vitro skin permeation and deposition of vitamin C. The topical
      delivery of magnesium ascorbyl phosphate, the pro-drug of vitamin C, was also
      examined in this study. All resurfacing techniques evaluated produced significant
      increases in the topical delivery of vitamin C across and/or into the skin. The
      erbium:yttrium-aluminum-garnet (Er:YAG) laser showed the greatest enhancement of
      skin permeation of vitamin C among the modalities tested. The laser fluence and
      spot size were found to play important parts in controlling drug absorption. An
      excellent correlation was observed in the Er:YAG laser fluence and transepidermal
      water loss, which is an estimation of skin disruption. Permeation of magnesium
      ascorbyl phosphate was not enhanced by the Er:YAG laser. The CO2 laser at a lower
      fluence promoted vitamin C permeation with no ablation of the stratum corneum or
      epidermal layers. Further enhancement was observed with the CO2 laser at higher
      fluences, which was accompanied by a prominent ablation effect. Microdermabrasion
      ablated the stratum corneum layers with minimal disruption of the skin barrier
      properties according to transepidermal water loss levels. The flux and skin
      deposition of vitamin C across microdermabrasion-treated skin was approximately
      20-fold higher than that across intact skin. The techniques used in this study
      may be useful for basic and clinical investigations of enhancement of topical
      vitamin C delivery.

PMID- 14708615
TI  - Differential regulation of cyclooxygenase-2 expression by phytosphingosine
      derivatives, NAPS and TAPS, and its role in the NAPS or TAPS-mediated apoptosis.
AB  - We investigated the effect of novel phytosphingosine derivatives, N-acetyl
      phytosphingosine (NAPS) and tetra-acetyl phytosphingosine (TAPS), on induction of
      apoptosis in HaCaT cells in comparison with C2-ceramide. NAPS/TAPS effectively
      decreased cell viability in a dose dependent manner mainly due to apoptosis. An
      apoptosis expression array analysis showed that in the TAPS treated cells 13
      genes including COX-2 encoding cyclooxygenase-2, the most induced by TAPS, were
      up-regulated while 23 others down-regulated. Therefore, we examined the mechanism
      underlying the altered expression of COX-2. Assays with inhibitors and antibodies
      against proteins involved in signal transduction demonstrated that NAPS and TAPS
      elevated COX-2 expression via tyrosine kinase, src, PI-3 kinase and PKC, followed
      by ERK activation. However, P38 was not involved in the NAPS-mediated COX-2
      expression but in the TAPS-mediated. We further demonstrated by FACS analyses
      that NAPS- or TAPS-mediated apoptosis was greatly increased in cells treated with
      celecoxib, a selective COX-2 inhibitor. Inhibition of the ERK pathway apparently
      involved in the NAPS/TAPS-mediated COX-2 expression enhanced the NAPS/TAPS
      mediated apoptosis, whereas inhibition of the P38 pathway did not. These results
      suggest that expression of COX-2 in the TAPS- or NAPS-treated cells may be
      increased to counteract the effect of those compounds on apoptosis.

PMID- 14708616
TI  - Tetraacetyl phytosphingosine-induced caspase activation and apoptosis occur
      through G2 arrest in human keratinocyte HaCaT cells.

PMID- 14708617
TI  - Iontophoresis and sonophoresis stimulate epidermal cytokine expression at
      energies that do not provoke a barrier abnormality: lamellar body secretion and
      cytokine expression are linked to altered epidermal calcium levels.
AB  - We performed this study to identify whether the expression of epidermal cytokines
      is altered by changes in epidermal calcium content, independent of skin barrier
      disruption. Iontophoresis and sonophoresis with the energies that do not disrupt
      the skin barrier, but induce changes in the epidermal calcium gradient, were
      applied to the skin of hairless mice. Immediately after iontophoresis and
      sonophoresis, immersion in a solution containing calcium was carried out, and
      iontophoresis in either high- or low-calcium solutions was performed. The biopsy
      specimens were taken for real-time quantitative RT-PCR to detect changes in mRNA
      level of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha),
      and transforming growth factor-beta in the epidermis and for immunohistochemical
      stain with primary antibodies to IL-1alpha and TNF-alpha. The expression of each
      cytokine mRNA increased in the epidermis treated with iontophoresis and
      sonophoresis compared to a nontreated control as well as in tape-stripped skin
      used as a positive control and was lower after immersion in a high-calcium
      solution than in low-calcium solution. IL-1alpha and TNF-alpha
      immunohistochemical protein staining increased with iontophoresis at low calcium.
      These studies suggest that changes in epidermal calcium can directly signal
      expression of epidermal cytokines in vivo, independent of changes in barrier
      function.

PMID- 14708618
TI  - Purinergic receptors are part of a signaling system for keratinocyte
      proliferation, differentiation, and apoptosis in human fetal epidermis.
AB  - We have investigated the expression of P2X5, P2X7, P2Y1, and P2Y2 receptor
      subtypes in 8- to 11-wk-old human fetal epidermis in relation to markers of
      proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67), keratinocyte
      differentiation (cytokeratin K10 and involucrin), and markers of apoptosis (TdT
      mediated dUTP nick end labeling (TUNEL) and anti-caspase-3). Immunohistochemistry
      showed that each of the four receptors was expressed in spatially distinct zones
      of the developing epidermis: P2Y1 receptors were found in the basal layer, P2X5
      receptors were predominantly in the basal and intermediate layers, and both P2Y2
      and P2X7 receptors were in the periderm. Colocalization experiments suggested
      different functional roles for these receptors. P2Y1 receptors were found in
      fetal keratinocytes positive for PCNA and Ki-67, suggesting a role in
      proliferation. P2X5 receptors double labeled with differentiated fetal
      keratinocytes that were positive for cytokeratin K10, suggesting a role in
      differentiation. P2X7 receptors colocalized with anti-caspase-3 antibody and were
      also expressed in periderm cells positive for TUNEL, suggesting a role in
      periderm cell apoptosis. P2Y2 receptors were found only in periderm cells and may
      have a role in chloride and fluid secretion into the amniotic fluid.

PMID- 14708619
TI  - Human melanoblasts in culture: expression of BRN2 and synergistic regulation by
      fibroblast growth factor-2, stem cell factor, and endothelin-3.
AB  - The BRN2 transcription factor (POU3F2, N-Oct-3) has been implicated in
      development of the melanocytic lineage and in melanoma. Using a low calcium
      medium supplemented with stem cell factor, fibroblast growth factor-2, endothelin
      3 and cholera toxin, we have established and partially characterised human
      melanocyte precursor cells, which are unpigmented, contain immature melanosomes
      and lack L-dihydroxyphenylalanine reactivity. Melanoblast cultures expressed high
      levels of BRN2 compared to melanocytes, which decreased to a level similar to
      that of melanocytes when cultured in medium that contained phorbol ester but
      lacked endothelin-3, stem cell factor and fibroblast growth factor-2. This
      decrease in BRN2 accompanied a positive L-dihydroxyphenylalanine reaction and
      induction of melanosome maturation consistent with melanoblast differentiation
      seen during development. Culture of primary melanocytes in low calcium medium
      supplemented with stem cell factor, fibroblast growth factor-2 and endothelin-3
      caused an increase in BRN2 protein levels with a concomitant change to a
      melanoblast-like morphology. Synergism between any two of these growth factors
      was required for BRN2 protein induction, whereas all three factors were required
      to alter melanocyte morphology and for maximal BRN2 protein expression. These
      finding implicate BRN2 as an early marker of melanoblasts that may contribute to
      the hierarchy of melanocytic gene control.

PMID- 14708620
TI  - Mutations of the BRAF gene in benign and malignant melanocytic lesions.
AB  - A single-point mutation in exon 15 of the BRAF gene has recently been reported in
      a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas
      examined. To evaluate the impact of the T1796A BRAF mutation, we screened primary
      melanomas, various types of nevi and lesions where a melanoma developed in an
      underlying nevus. We could detect the mutation in 28 of 97 (29%) melanomas and in
      39 of 187 (21%) nevi, including blue nevi (0/20) and Spitz nevi (0/69), which did
      not carry the mutation. In melanomas with an underlying nevus, either the
      mutation was present in both the laser-microdissected nevus cells and the laser
      microdissected melanoma cells (3/14) or both lesions were negative for the BRAF
      mutation except one case. In conclusion, mutations in exon 15 of the BRAF gene
      are nonspecific for progression of a nevus to a melanoma. Other so far unknown
      cofactors seem to be of importance.

PMID- 14708621
TI  - Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B
      radiation.
AB  - Retinyl esters, a storage form of vitamin A, concentrate in the epidermis, and
      absorb ultraviolet radiation with a maximum at 325 nm. We wondered whether these
      absorbing properties of retinyl esters might have a biologically relevant filter
      activity. We first used an in vitro model to assess the photoprotective
      properties of retinyl palmitate. We then applied topical retinyl palmitate on the
      back of hairless mice before exposing them to 1 J per cm2 ultraviolet B, and
      assayed the levels of thymine dimers produced in epidermal DNA 2 h following
      ultraviolet B exposure. Finally, we applied topical retinyl palmitate or a
      sunscreen on the buttocks of human volunteers before exposing them to four
      minimal erythema doses of ultraviolet B; we assayed the levels of thymine dimers
      produced 2 h following ultraviolet B exposure, and determined the intensity of
      erythema 24 h after ultraviolet B. In vitro, retinyl palmitate was shown to be as
      efficient as the commercial filter octylmethoxycinnamate in preventing
      ultraviolet-induced fluorescence or photobleaching of fluorescent markers. The
      formation of thymine dimers in mouse epidermis was significantly inhibited by
      topical retinyl palmitate. In human subjects, topical retinyl palmitate was as
      efficient as a sun protection factor 20 sunscreen in preventing sunburn erythema
      as well as the formation of thymine dimers. These results demonstrate that
      epidermal retinyl esters have a biologically relevant filter activity and
      suggest, besides their pleomorphic biologic actions, a new role for vitamin A
      that concentrates in the epidermis.

PMID- 14708622
TI  - S100A8 induction in keratinocytes by ultraviolet A irradiation is dependent on
      reactive oxygen intermediates.
AB  - Cutaneous exposure to ultraviolet (UV) A (320-400 nm) results in the formation of
      damaging reactive oxygen intermediates, which are implicated as mediators of DNA
      damage, apoptosis, and photoaging. S100A8 is a low-molecular-weight calcium
      binding protein, highly sensitive to oxidation. In this study, UVA-induced S100A8
      expression by keratinocytes was investigated. UVA (50-100 kJ per m2) strongly
      induced S100A8 in differentiated keratinocytes in the epidermis of BALB/c mice.
      Similarly, S100A8 mRNA and monomeric protein were significantly upregulated in
      PAM212 cells (a murine keratinocyte cell line) in response to 10 kJ per m2 UVA 24
      h after irradiation. Although S100A9 associates with S100A8 in neutrophils and
      abnormally differentiated keratinocytes (human psoriasis), in this study it was
      not coinduced with keratinocyte S100A8. Dorsal application of 4-hydroxy-tempo (a
      superoxide dismutase-mimicking agent) to mice concentration-dependently reduced
      UVA-induced S100A8 expression. Incubation of PAM212 cells with superoxide
      dismutase and catalase during UVA irradiation also abrogated S100A8 induction.
      These results suggest that UVA-induced S100A8 is expressed by keratinocytes in
      response to generation of reactive oxygen intermediates.

PMID- 14708623
TI  - Mice with genetically determined high susceptibility to ultraviolet (UV)-induced
      immunosuppression show enhanced UV carcinogenesis.
AB  - To assess the premise that genetically determined differences in susceptibility
      to UV-induced immunosuppression are reflected in UV carcinogenesis, we
      investigated UV skin cancer induction in two strains of reciprocal F1 hybrid mice
      CB6F1 males with high susceptibility to UV immunosuppression and a BALB/c X
      chromosome and B6CF1 males with low susceptibility to UV immunosuppression and a
      C57BL/6 X-chromosome. Four experimental groups comprising both strains treated
      three times weekly with two UV regimens (daily doses incremented from 2.25 to 6
      or 4.5 to 12 kJ per m2) were monitored for skin tumor development. Survival
      without a skin tumor differed over the four groups (p < 0.0001) and differed
      according to UV regimen within each strain (p < 0.0005). Differences between
      strains were significant for the higher dose (p = 0.03) but not for the lower
      dose (p = 0.19) of UV, suggesting a dose-strain interaction. Comparing the higher
      UV dose regimen to the lower UV dose regimen within a strain at three reference
      points, tumor-free survival was reduced significantly more (p < 0.05) in the
      CB6F1 mice than in the B6CF1 mice. Histologic assessment of all tumors revealed
      fibrosarcomas, squamous carcinomas, and mixed tumors. Immunohistochemistry of the
      mixed tumors for vimentin, keratin, and E-cadherin confirmed the presence of
      squamous and fibrosarcomatous elements. The enhanced susceptibility to UV
      carcinogenesis of CB6F1 males treated with the higher UV protocol was
      attributable to a significantly enhanced proportion (p < 0.005) of mixed tumors.
      Analysis of the data by comparing the proportion of animals tumor free at three
      reference time points confirmed a dose-strain interaction only in the development
      of mixed tumors, putatively the malignantly advanced carcinomas (p < 0.03). A
      dose-strain interaction was also observed for systemic UV immunosuppression of
      contact hypersensitivity (p < 0.025). These findings support the concept that
      genetic differences in susceptibility to UV-induced immunosuppression may be a
      risk factor for skin cancer.

PMID- 14708624
TI  - Abrogation of E-cadherin-mediated adhesion induces tumor cell invasion in human
      skin-like organotypic culture.
AB  - The role of cell-cell adhesion in the transition from premalignancy to invasive
      cancer is not well understood. The purpose of this study was to determine how
      abrogation of E-cadherin-mediated adhesion influenced early neoplastic
      progression in tissues that mimic human, premalignant disease. To accomplish
      this, E-cadherin function was abrogated in a human cell line representing an
      early stage in the transformation process (HaCaT-II-4 cells) that was grown in
      three-dimensional, organotypic cultures with intact basement membrane. Before
      modification, this cell line showed a paucity of cell adhesion structures by
      ultrastructural and immunohistochemical analysis, whereas immunoblot studies
      demonstrated that expression and association of E-cadherin and catenins were not
      diminished when compared with normal keratinocytes. To further reduce functional
      E-cadherin, II-4 cells were infected with a dominant-negative, recombinant
      adenovirus, expressing E-cadherin lacking an extracellular domain (AdECadEC).
      AdECadEC infection resulted in loss of endogenous E-cadherin and completely
      disrupted II-4 cell adhesion, as seen by loss of beta-catenin from II-4 cell
      junctions in monolayer culture. In three-dimensional cultures, AdECadEC-infected
      cells demonstrated disruption of tissue architecture, loss of cell-cell adhesion,
      and the invasion of individual tumor cells into the stroma. The induction of this
      invasive phenotype was associated with loss of basement membrane integrity, as
      seen by degradation of type IV collagen and laminin 5. These studies showed that
      loss of E-cadherin-mediated adhesion enabled acquisition of an invasive
      phenotype, suggesting that maintenance of intercellular adhesion and tissue
      organization plays a crucial part in suppressing the incipient stages of squamous
      cell cancer progression.

PMID- 14708625
TI  - Induction of interferon regulatory factor 1 expression in human dermal
      endothelial cells by interferon-gamma and tumor necrosis factor-alpha is
      transcriptionally regulated and requires iron.
AB  - Interferon regulatory factor-1 is a transcription factor that is linked to the
      expression of genes important in the initiation of the inflammatory response and
      the control of cell cycle. In this study, we determined that the generation of
      interferon regulatory factor-1 expression in human dermal microvascular
      endothelial cells was transcriptionally mediated by tumor necrosis factor-alpha
      or interferon-gamma via iron-dependent pathways. The induction of interferon
      regulatory factor-1 protein and the up-regulation of interferon regulatory factor
      1 mRNA levels was inhibited when cells were pretreated with the iron chelators 2
      2-dipyridyl or deferoxamine. This inhibition of interferon regulatory factor-1
      expression was associated with loss of interferon regulatory factor-1 binding to
      the interferon-stimulated response element as assessed by electrophoretic
      mobility shift assay. Addition of exogenous iron with the iron chelator resulted
      in reconstitution of cytokine responsiveness, thus demonstrating iron as the
      target for the chelator effect. Both tumor necrosis factor-alpha and interferon
      gamma-induced interferon regulatory factor-1 gene transcription, as assessed by
      the measurement of unspliced, nascent, heterogeneous nuclear RNA, and treatment
      with iron chelators blocked tumor necrosis factor-alpha or interferon-gamma
      mediated interferon regulatory factor-1 gene transcription. Iron was not
      essential, however, for the association of interferon regulatory factor-1 mRNA
      with polyribosomes, suggesting iron was not essential for interferon regulatory
      factor-1 protein translation. Through such inhibitory regulation on pro
      inflammatory transcription factors, iron chelators may serve as anti-inflammatory
      agents.

PMID- 14708626
TI  - Endurance training enhances vasodilation induced by nitric oxide in human skin.
AB  - Endurance training modifies the thermoregulatory control of skin blood flow, as
      manifested by a greater augmentation of skin perfusion for the same increase in
      core temperature in athletes, in comparison with sedentary subjects. In this
      study, we tested the hypothesis that a component of this adaptation might reside
      in a higher ability of cutaneous blood vessels to respond to vasodilatory
      stimuli. We recruited healthy nonsmoking males, either endurance trained or
      sedentary, in two different age ranges (18-35 y and >50 y). Skin blood flow was
      measured in the forearm skin, using a laser Doppler imager, allowing to record
      the vasodilatory responses to the following stimuli: iontophoresis of
      acetylcholine (an endothelium-dependent vasodilator), iontophoresis of sodium
      nitroprusside (a nitric oxide donor), and release of a temporary interruption of
      arterial inflow (reactive hyperemia). There was no effect of training on reactive
      hyperemia or the response to acetylcholine. In contrast, the increase in
      perfusion following the iontophoresis of sodium nitroprusside, expressed in
      perfusion units, was larger in trained than in sedentary subjects (younger: 398
      +/- 54 vs 350 +/- 87, p < 0.05; older 339 +/- 72 vs 307 +/- 66, p < 0.05). In
      conclusion, endurance training enhances the vasodilatory effects of nitric oxide
      in the human dermal microcirculation, at least in forearm skin. These
      observations have considerable physiologic interest in view of recent data
      indicating that nitric oxide mediates in part the cutaneous vasodilation induced
      by heat stress in humans. Therefore, the augmentation of nitric oxide bioactivity
      in the dermal microcirculation might be one mechanism whereby endurance training
      modifies the thermoregulatory control of skin blood flow.

PMID- 14708627
TI  - Topically applied imiquimod inhibits vascular tumor growth in vivo.
AB  - Vascular tumors occur in approximately 10% of all infants and may be associated
      with significant morbidity. Available therapies for vascular tumors, such as
      systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity,
      limiting their use to complicated cases. Using a mouse hemangioendothelioma
      model, we investigated the efficacy and mechanism of action of imiquimod, a
      topically applied inducer of cytokines. Application of imiquimod cream, whether
      initiated at the time of cell inoculation or when tumors became visible,
      significantly decreased tumor growth and increased animal survival in comparison
      with control mice. Imiquimod-treated tumors showed decreased tumor cell
      proliferation, increased tumor apoptosis, and increased expression of tissue
      inhibitor of matrix metalloproteinase-1 with decreased activity of matrix
      metalloproteinase-9. The demonstration that local application of imiquimod
      inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a
      novel, less toxic means of treating infantile hemangioendotheliomas and perhaps
      other cutaneous vascular tumors.

PMID- 14708628
TI  - A novel role of fibrin in epidermal healing: plasminogen-mediated migration and
      selective detachment of differentiated keratinocytes.
AB  - Recent studies have shown that fibrin promotes epidermal regeneration in vitro
      and maintains the stem cell population after transplantation of keratinocytes in
      vivo. As epidermal keratinocytes do not express integrin alpha(v)beta3, the
      receptor for fibrin and fibrinogen, the mechanism through which fibrin affects
      epidermal cells remains elusive. To investigate the role of fibrin in epidermal
      wound healing, we developed an in vitro model in which fibrin was added to the
      top of wounded keratinocyte monolayers grown on collagen. With this matrix
      topology, keratinocytes migrate between the collagen on their basal side and
      fibrin on their apical side mimicking migration of the epidermis in vivo. Using
      this model, we found that fibrin promoted keratinocyte migration in low and high
      calcium concentrations by exposing the cells to plasminogen. The migration rate
      depended strongly on the concentration of fibrinogen and the rate of plasmin
      mediated fibrin degradation. Surprisingly, fibrin and fibrinogen caused
      significant detachment of keratinocytes which was prevented by the addition of
      calcium. Further examination using flow cytometry revealed that the detached
      cells were larger, more granular, and had very low levels of beta1 integrin,
      which are all signs of differentiated keratinocytes. Our results suggest a novel
      dual role of fibrin in epidermal healing. First, fibrin promotes keratinocyte
      migration indirectly by exposing plasminogen to migrating cells, and second,
      fibrin selectively disrupts adhesion of differentiated keratinocytes. Our data
      are novel and may have important implications in understanding wound healing and
      in the use of fibrin as a biomaterial for protein and gene delivery.

PMID- 14708629
TI  - Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular
      dystrophy.
AB  - Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive
      disorder characterized by abnormal growth of scalp hair during infancy, and by
      the later occurrence of macular degeneration leading to blindness during the
      first to third decade of life. Hypotrichosis with juvenile macular dystrophy was
      recently shown to result from mutations in CDH3 encoding P-cadherin. In this
      study, we assessed 27 individuals, including nine patients, belonging to five
      families in an attempt to characterize further the CDH3 mutation spectrum and
      delineate possible phenotype-genotype correlations. Deleterious biallelic
      mutations, predicted to lead to the translation of a dysfunctional protein, were
      found in all affected individuals. Four of these mutations are novel. Affected
      individuals of two large separate apparently unrelated families of Arab Israeli
      origin were found to carry the same homozygous mis-sense mutation (R503H) in exon
      11 of the CDH3 gene. This mutation, which alters a Ca2+-binding site in the
      fourth extracellular domain of P-cadherin, was previously described in a third
      unrelated Arab Israeli family. Using haplotype analysis for a series of
      polymorphic markers encompassing the CDH3 gene, we obtained evidence suggesting a
      founder effect for R503H in the Arab Israeli population. We also compared the
      dermatologic and ophthalmologic features of 22 hypotrichosis with juvenile
      macular dystrophy patients with known recessive mutations in CDH3. Whereas hair
      paucity and macular degeneration were found in all patients, we noticed
      significant interfamilial and intrafamilial differences in hair morphology,
      associated skin findings as well as severity and age of onset of visual
      disability. Altogether, our results obtained in a series of families of various
      ethnic origins firmly establish mutations in CDH3 as the proximal cause of
      hypotrichosis with juvenile macular dystrophy and demonstrate genetic homogeneity
      as well as phenotypic heterogeneity in this disorder.

PMID- 14708630
TI  - CD34 in human hair follicle.

PMID- 14708631
TI  - A novel GJB2 (connexin 26) mutation, F142L, in a patient with unusual
      mucocutaneous findings and deafness.

PMID- 14708632
TI  - Structure and heterogeneity of the human gene for epiplakin (EPPK1).

PMID- 14708633
TI  - Propionibacterium acnes-reactive T helper-1 cells in the skin of patients with
      acne vulgaris.

PMID- 14708634
TI  - Tightening tight junctions with compression therapy.

PMID- 14708635
TI  - Inhibition of vascular cell adhesion molecule-1 expression in human dermal
      microvascular endothelial cells by iron chelators.

PMID- 14708636
TI  - CD34 microvessel density and VEGF expression in basal and squamous cell
      carcinoma.
AB  - Angiogenesis is a central process in the growth of solid tumors. The purpose of
      our study was to analyze the angiogenic pattern in squamous and basal cell
      carcinomas and to point out differences in microvessel density that could explain
      their different biological behaviour. Thirty-nine skin tumors (26 basal and 13
      squamous cell carcinomas) were analyzed. In all samples, the microvessels density
      (MVD) and the levels of vascular endothelial growth factor mRNA (VEGFmRNA) were
      analyzed, together with the inter-relationship between these two variables. Using
      the median value of the entire series (33 vessels per 2.22 mm2), tumors with low
      and high MVD were identified. The majority of cancers with high vascularization
      belonged to the squamous histotype (12 of 39), while 19 of the 26 basal cell
      carcinomas showed a lower number of microvessels than the median value (p =
      0.0001). The median value of VEGFcDNA quantitation allowed us to distinguish
      tumors with high VEGF expression (> 470 molecules cDNA) from those with low (< or
      = 470 molecules) VEGF expression: 20 of the 26 basal cell carcinomas showed low
      VEGF expression, while 11 of the 13 squamous cell carcinomas showed high VEGFcDNA
      levels (p = 0.0003). Moreover, a significant association between a high
      microvessel density and high VEGFmRNA levels (p = 0.006) was found. Furthermore,
      when studying VEGF expression by immunohistochemistry, we obtained similar
      results and noted a correlation with VEGFmRNA expression (p < 0.0001). The
      association between high vascularization, high VEGF levels, and squamous cell
      histotype suggests the possible role of neoangiogenesis in determining the more
      aggressive biological behaviour of this type of cancer.

PMID- 14708637
TI  - Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological
      and immunohistochemical study of 12 cases.
AB  - Basaloid squamous carcinoma (BSC) is a rare variant of squamous cell carcinoma
      (SCC). In this study, clinicopathological and immunohistochemical characteristics
      of 12 superficial esophageal BSCs were examined and compared with those of
      typical superficial SCCs. Eight cases were classified into an elevated type, and
      the other four into a depressed type. High-grade intraepithelial neoplasia was
      not observed around the invasive lesions in five cases, and only BSC components
      were apparent. High-grade intraepithelial neoplasia was demonstrated in seven
      cases, five of which had both BSC and SCC components in the invasive lesion. A
      cribriform growth pattern, comedo-type necrosis, and hyaline deposits were
      conspicuous histological findings. CK14 was positively stained in 90% of the
      series, but the proportion of positive cells was small in most cases. Type IV
      collagen was increased or well preserved in the basement membrane in 70% of
      cases, but heparan sulfate was decreased in the majority. In comparison with
      SCCs, lymphatic permeation was observed less frequently. However, regarding the
      frequencies of venous permeation, nodal metastasis, p53 protein expression, and
      Ki-67 labeling index, no significant differences were noted. Thus, esophageal
      BSCs demonstrate the pathological features characteristic of an early stage, but
      pathological parameters related to biological behavior do not significantly vary
      from those typical of SCCs.

PMID- 14708638
TI  - Subcellular expression of c-IAP1 and c-IAP2 in colorectal cancers: relationships
      with clinicopathological features and prognosis.
AB  - The Inhibitor of Apoptosis Protein (IAP) family includes several critical cell
      death inhibitors, the expression of which could be involved in colorectal
      carcinogenesis. Among them, c-IAP1 and c-IAP2 expression has never been
      investigated in colorectal cancer. The present study was designed to determine
      whether expression of both IAPs was related to pathological parameters and
      survival in sporadic colon carcinomas. Analysis of five human colon cancer cell
      lines by both western blotting of cell fractions and immunocytochemistry showed
      that the two IAPs could be expressed both in the nucleus and in the cytoplasm.
      Immunohistochemical analysis of a series of 46 sporadic colorectal
      adenocarcinomas demonstrated that c-IAP1 expression was more frequent in the
      nucleus (85%), and that c-IAP2 was more often expressed in the cytoplasm (82%). A
      significant association was identified between a strong lymphoid infiltrate in
      the stroma and the nuclear expression of c-IAP2 (p = 0.02). No other relationship
      was observed between IAP expression and pathological features. After adjusting by
      age and stage, the relative risk of death was lower for cytoplasmic c-IAP1,
      cytoplasmic c-IAP2, and nuclear c-IAP2 expression. It was higher for nuclear c
      IAP1 expression. These associations were not statistically significant, but this
      work underlines the importance of taking into account the subcellular location of
      the IAP family members in the evaluation of their prognostic significance.

PMID- 14708639
TI  - Effects of long-term administration of Senna occidentalis seeds in the large
      bowel of rats.
AB  - Plants of the genus Senna that contain anthranoides derivatives are frequently
      used as cathartics. Radiological studies have demonstrated that patients with
      chronic constipation who have used stimulant laxative have colonic redundancy and
      dilatation more frequently than patients who have not. The objective of the
      present work was to study morphological and histochemical changes of the lower
      gut after administration of Senna occidentalis seeds for a long period to rats,
      as observed in skeletal muscle fibers. Fragments of the lower gut of young and
      adult rats treated with S. occidentalis seeds (2% for 171 days and 3% for 61 days
      in the diet) were submitted to histological and histochemical analysis and to
      densitometry. The most important finding was decreased oxidative enzyme activity
      in smooth muscle cells and in myenteric neurons of the large bowel. As oxidative
      metabolism is essential for ATP and energy production, these results suggest that
      the functional intestinal disturbance caused by the chronic use of Senna
      occidentalis as a laxative can be due to a metabolic effect involving energy
      production, which would decrease colonic motility and cause functional colonic
      dilatation, but without any irreversible anatomic change.

PMID- 14708640
TI  - Unusual splenic metastasis from renal cell carcinoma. A case report and review of
      the literature.
AB  - This is a short report on a splenic metastasis from renal cell carcinoma.
      Previously, the patient had renal carcinoma removed by nephrectomy. The diagnosis
      of metastasis was based on morphology and immunohistochemistry. It is certainly
      true that splenic metastases from renal cell carcinoma are rare. Nevertheless,
      they have been well described in the literature. A giant cell reaction to tumor
      is noted in a number of cancers and mainly represents an unusual phenotype.

PMID- 14708641
TI  - Malignant lymphoma of the stomach in association with inflammatory
      myofibroblastic tumor of the spleen. A case report.
AB  - We report on a case of a 40-year-old male patient who underwent a gastrectomy
      because of a biopsy-proven large B-cell lymphoma of the stomach. On surgery, a
      nodule in the spleen also was noted. Grossly and microscopically, the two lesions
      were different: the tumor of the stomach appeared white-gray on the cut surface
      and was a centroblastic variant of diffuse large B-cell lymphoma. Histologically,
      one perigastric lymph node was involved. Grossly, the splenic nodule was gray
      yellow and had a histological appearance of an inflammatory myofibroblastic tumor
      (IMT). The association between malignant tumor and IMT is rare. In such an
      association, the latter lesion most often has been reported in the spleen. As EBV
      may be involved in the genesis of both lymphoma and IMT, we tested both lesions
      for its presence using in situ hybridization, but the tests were negative. It
      remains to be verified whether the association between lymphoma and IMT is more
      than fortuitous.

PMID- 14708642
TI  - Primitive neuroectodermal tumor (PNET) of the urinary bladder.
AB  - We report on the clinical, morphologic, immunohistochemical, ultrastructural, and
      molecular cytogenetic features of a primitive neuroectodermal tumor (PNET)
      primarily arising in the urinary bladder. An 81-year-old man presented with
      lymphedema of the lower extremities, fatigue, and urge incontinence.
      Radiographically, a tumor filling the entire cavity of the urinary bladder and
      extending into the pelvic and retroperitoneal tissue was noted. Histology of
      tumor biopsies showed a highly cellular, focally necrotic small round-cell tumor
      with numerous mitoses and occasional rosette-like structures. The tumor cells
      displayed significant immunoreactivity for neuron-specific enolase (NSE) and the
      MIC2 gene product (CD99). Dense-core granules were detectable by electron
      microscopy. A molecular cytogenetic analysis using comparative genomic
      hybridization (CGH) revealed gains of the chromosomes 3p, 6, 8q, 12, 17q, and
      21q. The patient died two weeks after diagnosis. To the best of our knowledge,
      this is the fifth reported case of a PNET of the urinary bladder, and the first
      that includes a molecular cytogenetic analysis based on CGH.

PMID- 14708643
TI  - Unusual clinical manifestation of virus-associated hemophagocytic syndrome.
AB  - A 22-year-old man presented with bilateral painless cervical lymphadenomegaly,
      difficulties in nasal breathing and bilateral conductive hearing loss. Rhinoscopy
      and computer tomography disclosed mucosal polyps in the nasal cavity and a
      polypoid soft mass almost completely filling the whole nasal cavity and the
      paranasal sinuses. Thoracic and abdominal computer tomography showed mild
      hepatosplenomegaly and a solitary round lesion in the right lung. No fever or
      abnormal laboratory parameters were detected. The biopsy from the nasal polypoid
      lesions and from the cervical lymph nodes showed extensive proliferation of
      histologically benign erythrophagocytic histiocytes. The diagnosis of virus
      (Epstein-Barr virus)-associated hemophagocytic histiocytosis was confirmed by
      immunohistochemical reactions, by polymerase chain reaction, and by Epstein-Barr
      Encodes (Early)-RNA in situ hybridization. This case illustrates an unusual
      clinical manifestation of virus-associated hemophagocytic histiocytosis
      presenting as mucosal polyps of the upper respiratory tract.

PMID- 14708644
TI  - Chance diagnosis of low stage non-metastasized adrenal cortical carcinoma in a
      young woman with retroperitoneal hemorrhage.
AB  - Adrenal cortical carcinoma (ACC), a rare and highly malignant neoplasm of the
      cortical tract of the adrenal gland, is usually diagnosed at an advanced stage of
      development and often when metastatic spread already has begun. We report a very
      rare case of low-stage, non-metastasized ACC, the first clinical appearance of
      which was a large retroperitoneal hemorrhage caused by the rupture of the
      neoplastic mass. To the best of our knowledge, this is the third reported case of
      ACC rupture.

PMID- 14708645
TI  - Pigmented composite paraganglioma-ganglioneuroma of the urinary bladder.
AB  - We report a case of a pigmented composite paraganglioma-ganglioneuroma of the
      urinary bladder in a 70-year-old female. Grossly, the tumor measured 6.5 cm in
      diameter and had arisen from the base of the urinary bladder. Histologically, the
      tumor was composed of approximately equal components of paraganglioma and
      ganglioneuroma, which were partly separated and partly mixed, and intermingled
      with each other. There were foci of ample dark brown pigmentation in the
      cytoplasm of chromaffin paraganglioma cells. The pigment was Masson-Fontana
      positive and had been bleached by hydrogen peroxide (H2O2). Electron microscopy
      showed large, abundant, pleomorphic electron-dense granules consistent with
      neuromelanin. In addition, there were numerous electron-dense neurosecretory-type
      granules. Neuromelanin, melanin or lipofuscin are occasionally observed in
      paragangliomas, although the occurrence of these pigments has never been
      described in a composite tumor originating from either adrenal medulla or
      extraadrenal paraganglia. To the best of our knowledge, our report represents the
      first case of pigmented composite paraganglioma-ganglioneuroma and expands the
      morphological spectrum of these unusual tumors.

PMID- 14708646
TI  - Dental and oral trauma and mouthguard use during sport activities in Israel.
AB  - The purpose of the present study was to evaluate the occurrence of oral and
      dental injuries in young Israeli population engaged in diverse sport activities.
      The participants' awareness of the use of protective devices, such as
      mouthguards, during sport activities was also evaluated. A population of 943
      young adults, 95% males and 5% females (ages 18-19), was surveyed. A
      questionnaire was distributed relating to the type of sport activity practised,
      past oral and dental injuries over their lifetime, specifying the time and type
      of sports in which the injury occurred and the use and awareness of the
      protective devices. Of the total population examined, 850 (90%) were active in at
      least one type of sport, either as professionals or as amateurs. The analysis
      included the population that regularly participated in at least one sporting
      activity. The most commonly practised sports were soccer (54% of all active
      participants) and basketball (50%). The total number of dental and oral injuries
      experienced during all sport activities was 229, affecting 27% of the
      participants of whom 73 (9%) suffered dental injuries. Most dental injuries
      occurred during the basketball and soccer training sessions and matches reaching
      42 and 41% of the total number of injuries, respectively, and affected 7.2 and
      6.6% of the basketball and soccer players. Traumatic dental injuries in other
      sports occurred in less than 7% of the participants in these activities. Only 27%
      of the participants were aware of the protective devices, such as a mouthguards,
      and only 3% actually used these devices. These results point to the high risk of
      potential dental and oral injury during sport activities, the little knowledge
      about the benefits of using mouthguards and their limited utilization. The
      importance of public health education to increase the awareness of protective
      measures and devices and their actual use in Israel is the main focus. It should
      be a combined duty of dentists and sports physicians and of the coaches to
      encourage the use of protective devices during training and games.

PMID- 14708647
TI  - A multicentre investigation into the role of structured histories for patients
      with tooth avulsion at their initial visit to a dental hospital.
AB  - A paper structured history (SH) is a sheet, which prompts or reminds the
      clinician to ask various important questions. The aim of this study was to
      examine avulsion cases with respect to the quality of clinical records. Hospitals
      studied used either a paper SH or had no specific structure in their recording of
      avulsion details, e.g. unstructured histories (USH). The most important
      prognostic items that should be recorded for avulsion cases at their first visit
      were identified by reviewing the literature. Clinical case records meeting strict
      inclusion criteria were retrospectively analyzed against 10 important prognostic
      items. Forty-seven patient records were identified in the SH group compared to 43
      patient records in the USH group. Using chi-square and Fisher's exact tests, the
      SH group were significantly better at recording the following: accident details
      (P < 0.001), loss of consciousness (P < 0.001), other teeth or tooth injuries (P
      < 0.05), extra-alveolar mediums (P < 0.01), total extra-alveolar time (P <
      0.001), antibiotics given at time of injury (P < 0.05) and apical maturity (P <
      0.001). In all the dental hospitals selected, two-thirds of the case records were
      completed by junior dentists not in specialist training and the improvement in
      history when using an SH form was most pronounced in these groups. It is
      concluded, therefore, that an SH should be taken for cases ofavulsion as it was
      significantly better at collecting essential prognostic information.

PMID- 14708648
TI  - Prevalence and handedness correlates of traumatic injuries to the permanent
      incisors in 13-17-year-old adolescents in Erzurum, Turkey.
AB  - The objectives of the present study were to explore the relationship between
      dental trauma and handedness, and to assess the prevalence of traumatic injuries
      to the permanent incisors of 13-17-year-old patients, seeking treatment for
      various dental conditions in Erzurum, Turkey. A questionnaire focusing on
      handedness was administered to these patients. Handedness was assessed by the
      Edinburgh Handedness Inventory (Oldfield, 1971). Hand preference was divided into
      two classes for convenience in data analysis: (i) right-handers (GSc from 80 to
      100); and (ii) left-handers (GSc from -80 to -100). This study included the 13-17
      year-old group patients who had GSc as described above. Thus, the present study
      was carried out on 2180 (1252 male and 928 female, with a mean age of 14.9 years)
      out of 2392 patients. The clinical examinations and radiographic assessments were
      performed in full-designed dental chairs. Preliminary analysis showed no
      differences in rates of handedness with respect to sex and age. Overall, 10.4% of
      the patients were left-handers. A total of 292 (13.4%) of 2180 patients examined
      had one or more traumatized permanent incisors. The proportion of dental trauma
      was significantly higher in males than in females, 17.41% in males as compared to
      7.97% in females; and ratio of the affected males to females was about 2.18. Sex
      difference in the prevalence of traumatized permanent incisors was statistically
      significant (P < 0.001). That is, males had a significantly higher risk of dental
      trauma than females (P < 0.001; odds ratio: 2.49; 95% confidence interval (CI)
      1.88, 3.23). There was a higher level of traumatized permanent incisors among
      left-handers than among right-handers. 28.3% of left-handers and 11.7% of right
      handers had dental trauma. This difference in the prevalence of traumatized
      permanent incisors for handedness was statistically significant (P < 0.001).
      Indeed, left-handers had a significantly higher risk on dental trauma than right
      handers (P < 0.001; odds ratio: 3.09; 95% CI 2.23, 4.29). The primary causative
      factor in the occurrence of trauma was the fall (27.7%). Then came violence and
      fight as the second most frequent cause of trauma (24%), followed by sports
      injury (18.8%). Trauma resulting from collisions and traffic accidents were
      accounted as 13.7 and 11.3% of all cases, respectively. The other causes were
      4.5%. In conclusion, the present study suggests that left-handed adolescents have
      more frequent permanent incisor tooth trauma than right-handed adolescents. Left
      handedness, therefore, appears to be a risk factor for trauma in 13-17-year-old
      adolescents.

PMID- 14708649
TI  - Influence of age on the behavior of dental pulp of dog teeth after capping with
      an adhesive system or calcium hydroxide.
AB  - This study evaluated histomorphologically the influence of chronological age of
      the dog on the dental pulp-healing process after capping with the All Bond 2
      system or with calcium hydroxide paste. The animals were divided according to age
      into young and adult groups. Class 5-type cavities were prepared, and the pulp
      was submitted to an exposure of a diameter of 0.5 mm. The pulp of the teeth was
      then protected with the adhesive system or with a calcium hydroxide paste. Sixty
      days after treatment, the results obtained with the adhesive system in the young
      group were significantly better than those in the adult group. With calcium
      hydroxide, the results were similar for both groups. The pulp treated with
      calcium hydroxide exhibited a complete hard tissue bridge and a pulp without
      inflammatory reaction, a fact not observed when the adhesive system was used. In
      conclusion, the chronological age of the pulp influenced the comparative results
      only for the adhesive system (P = 0.1), and the total results were better with
      calcium hydroxide than with the All Bond 2 system (P = 0.01).

PMID- 14708650
TI  - Root resorption in dental trauma: 45 cases followed for 5 years.
AB  - We aimed to: (i) study the prevalence of root resorption after luxation or
      avulsion injuries on permanent teeth referred to our dental clinic over a 3-year
      period; (ii) study the relationship between type of injury and resultant type of
      resorption complication; and (iii) evaluate success of treatment protocols for
      various resorption complications. We observed 1943 patients with dental trauma,
      aged between 2 and 26 years, referred to the Accident and Emergency Department of
      the Dental Clinic, University of Brescia, from 1st September 1997 to 31st
      December 2001. Of these, 261 permanent teeth had sustained luxation (n = 188) or
      avulsion (n = 73) injuries. Permanent teeth luxation and avulsion injuries
      occurred most often in upper incisors (75%) of patients mostly aged 12-21 years,
      with males more commonly affected than females (68.3% vs. 31.7%). These cases
      were followed for 5 years, and complications and response to treatment were
      recorded. Root resorption was observed in 45 (17.24%) of these cases. Of the 45
      cases with resorption, 9 were associated with luxation injury (20%) while 36
      (80%) with avulsion. We distinguished 30 cases of inflammatory root resorption
      (18 transient and 12 progressive) and 15 cases of ankylosis and osseous
      replacement. When resorption was recognized, quick and effective treatment could
      still result in an excellent functional and aesthetic outcome for these teeth.

PMID- 14708651
TI  - Clinical outcomes for permanent incisor luxations in a pediatric population. I.
      Intrusions.
AB  - A longitudinal outcome study was undertaken to identify variables that
      significantly influenced tooth survival as well as pulpal and periodontal
      outcomes for intruded permanent maxillary incisors of children and adolescents.
      All cases were treated between June 1988 and June 1998 in a teaching hospital
      clinic. Clinical and radiographic data were collected for 26 patients (19 males,
      7 females) that represented 31 permanent maxillary incisors. Mean age at the time
      of injury was 9.3 years (range = 5.5-17.8 years). Mean time elapsed to follow up
      was 1380 days (range = 65-3394 days). Survival analysis was used to identify
      variables significantly related to the survival and pulp necrosis (PN) for these
      incisors. Proportional hazards regression yielded significant prognostic models
      for tooth survival and the diagnosis of PN (P < 0.05). Incisors intruded > 6 mm
      had significantly decreased survival compared with incisors intruded < 3 mm (5
      year survival, 0.45 and 1.0, respectively, (P < 0.05)). Complex crown fractures
      were significantly related to the development of PN (P < 0.05). Logistic
      regression analysis showed that treatment method and severity of intrusion were
      related to the presence of replacement root resorption (P < 0.05). This study
      represents the largest sample of intruded permanent incisors examined in an
      outcome study of children and adolescents exclusively.

PMID- 14708652
TI  - Clinical outcomes for permanent incisor luxations in a pediatric population. II.
      Extrusions.
AB  - A longitudinal outcome study was undertaken to identify variables that
      significantly influenced outcomes for extruded permanent maxillary incisors of
      children and adolescents. Clinical and radiographic data was available for 35
      patients (18 males, 17 females) representing 55 incisors. Mean age at the time of
      injury was 10.6 years (range: 7.1-17.8 years). Mean time elapsed to follow up was
      1320 days (range: 423-2887 days). Survival analysis was used to identify
      variables significantly related to the prognosis of these teeth. The loss of an
      incisor following extrusion was uncommon as only one tooth (1/55) required
      extraction. There was no statistically significant difference in survival between
      severely extruded teeth and avulsions that had been stored in physiological media
      (P > 0.10). Pulp necrosis (PN) was the most common complication following injury
      (43%) and it most often occurred during the first year. Although not
      statistically significant, a trend towards increased PN was found with more
      severely extruded teeth (P = 0.20, relative risk = 2.08). Pulp canal obliteration
      (PCO) was the second most common outcome (35%). The degree of extrusion was
      proven to be significantly associated with the development of PCO (P = 0.03,
      relative risk = 0.33). Root resorption was an uncommon outcome (3/55). This study
      represents the first outcome data on extrusions to permanent maxillary incisors
      in an exclusively pediatric population.

PMID- 14708653
TI  - Clinical outcomes for permanent incisor luxations in a pediatric population. III.
      Lateral luxations.
AB  - A longitudinal outcome study was designed to identify variables that influenced
      tooth survival as well as pulpal and periodontal outcomes of laterally luxated
      permanent maxillary incisors of children and adolescents. All cases were treated
      between June 1988 and June 1998 in a teaching hospital clinic. Clinical and
      radiographic data were collected for 42 patients (26 males, 16 females) that
      represented 58 permanent maxillary incisors. Mean age at the time of injury was
      11.4 years (range: 6.3-17.8 years). Mean follow-up time was 1460 days (range: 183
      3905 days). In the entire sample (n = 58), no incisors required extraction.
      Survival analysis and logistic regression were used to identify variables
      significantly related to the survival and healing outcomes of these incisors.
      Pulp necrosis (PN) (40%) and pulp canal obliteration (PCO) (40%) were common
      healing complications. Proportional hazards (Cox) regression showed that PN
      develops within the first year. Logistic regression demonstrated that root
      development (P = 0.3, PN; P = 0.8, PCO) and extent of lateral luxation (P = 0.5,
      PN; P = 0.9, PCO) were not significantly related to PN and PCO. This study
      provides the first report of incisor survival in children and adolescents
      following lateral luxation injuries.

PMID- 14708654
TI  - Traumatic intrusion of maxillary permanent incisors into the nasal cavity
      associated with a seizure disorder: report of a case.
AB  - Childhood traumatic dental injury is typically associated with motor vehicle
      accidents, sports, or other recreational activities. However, seizure disorders
      or other compromising medical conditions may precipitate dental trauma. Complete
      intrusion injuries in the mixed or permanent dentition are relatively rare. This
      paper describes the case history of an adolescent male who sustained displacement
      of a lateral incisor into the nasal cavity and complete bony intrusion of the
      three other permanent maxillary incisors because of a fall following a seizure.
      Counseling on helmet/face-shield usage for seizure-susceptible patients must be
      provided and documented, particularly after sustaining traumatic injury.

PMID- 14708655
TI  - Transient apical breakdown following tooth luxation.
AB  - Transient apical breakdown is a sequelae of certain dental traumatic injuries
      where the injured tissues undergo a spontaneous process of repair with no
      permanent damage to the pulp. Misdiagnosis of this condition may result in
      unnecessary endodontic treatment. Presented is a case of transient apical
      breakdown following a subluxation injury of a maxillary central incisor in a 15
      year-old girl. Four months after injury, coronal discoloration, periapical
      radiolucency as well as negative pulp responses to cold and electric tests were
      still recorded. Subsequently, the tooth spontaneously regained its original shade
      and the pulp responded normally to pulp sensitivity tests. Methods for early
      diagnosis of transient apical breakdown are discussed.

PMID- 14708656
TI  - Orthodontic movement in traumatically intruded teeth: a case report.
AB  - Intrusive luxation of permanent mature teeth is one of the most serious injuries
      to the periodontal ligament in dental traumatology. Various treatment approaches
      are currently practised. The treatment of choice for traumatically intruded teeth
      was to combine orthodontic repositioning and endodontic treatment. This case
      report describes the treatment of a 50-year-old male patient, with four
      completely intruded mature permanent maxillary incisors. Orthodontic extrusion
      was initiated 1 week after the trauma. After 10 days, the crowns of the teeth
      were exposed to start endodontic therapy. Nine weeks after the injury and 8 weeks
      after the beginning of orthodontic extrusion, the intruded incisors were back
      about to their original position before the displacement occurred. All treatment
      management as well as a follow-up 8 years after the trauma are described.

PMID- 14708657
TI  - Repair of untreated horizontal root fracture: a case report.
AB  - We report a clinical case of horizontal root fracture in the mandibular first
      premolar induced by a traffic accident. The fractured tooth spontaneously healed
      and diagnosed radiographically after 2 years. Fractured fragments were separated
      by a narrow radiolucent line and the edges were rounded, and healing of the tooth
      is likely to be related to interproximal connective tissue healing. Our case is
      an example of spontaneously healed fracture roots. An interesting finding is that
      the healing was observed even in the presence of two root canals, the vitality of
      the pulp was preserved and displacement of fragments were prevented.

PMID- 14708658
TI  - Potential of solid phase extraction disks to aid determination of dislodgeable
      foliar residues of chlorpyriphos, malathion, diazinon, and acephate.
AB  - The utility of solid phase extraction (SPE) for concentrating four
      organophosphate insecticides from solutions of water and sodium dioctyl
      sulfosuccinate, a surfactant, was evaluated. Reverse phase (C18, octadecyl bonded
      silica) sorbent in the form of a disk was the SPE medium evaluated.
      Chlorpyriphos, malathion, and diazinon, but not acephate, were retained on and
      eluted from the SPE disks. For pesticides that were retained on SPE disks,
      recoveries from the disks were equal to or higher than recoveries achieved by
      solvent partitioning. Dislodgeable foliar residues of acephate were successfully
      concentrated for analysis by lyophilization of water-surfactant solutions.
      Recoveries of pesticides from SPE disks stored at -15 degrees C for one week were
      equal to or higher than those of pesticides stored in water-surfactant for one
      week at -15 degrees C. Malathion- and diazinon-fortified samples in
      watersurfactant and on SPE disks were prepared in one state and shipped for
      analysis in another state. Pesticides in the water-surfactant samples were
      concentrated by solvent partitioning and were underestimated by 41% (diazinon)
      and 16% (malathion). Conversely, diazinon samples on the SPE disks were on
      average underestimated by 3% and malathion was overestimated by an average of
      55%. The overestimation of malathion was attributed to a matrix effect during
      analysis associated with the presence of surfactant, which was retained on and
      subsequently eluted from the SPE disks. The retention of surfactant by the SPE
      disks and its subsequent elution may considerably limit their usefulness in
      determination of dislodgeable foliar residues.

PMID- 14708659
TI  - Water characterization and seasonal heavy metal distribution in the Odiel River
      (Huelva, Spain) by means of principal component analysis.
AB  - The Iberian Pyrite Belt is the largest mass of sulfide and manganese ores in
      Western Europe. Its sulfide oxidation is the origin of a heavily acidic drainage
      that affects the Odiel River in southwestern Huelva (Spain). To assess
      physicochemical, contamination parameters, heavy metal distribution and its
      seasonal variation in the upper Odiel River and in El Lomero mines, three water
      samplings were undertaken and analyzed between July 1998 and November 1999. Water
      from the Odiel River in the polluted zone showed low pH values (2.76-3.51), high
      heavy metal content, and high values of conductivity (1410-3648 microS/cm) and
      dissolved solids (1484-5602 mg/L). Principal Component Analysis (PCA) showed that
      variables related with the products of the pyrite oxidation and the salts that
      are solubilized by the high acidity generated in the oxidation of sulfides,
      grouped in the first component, accounted for 40.88% of total variance, and were
      the main influential factor in physicochemical water sample properties. The
      second influential factor was minority metals (nickel, cobalt, cadmium). Heavy
      metals showed three different seasonal patterns, closely related with saline
      efflorescences formed next to the river bed: majority metals (iron, copper,
      manganese, zinc); minority metals (lead, nickel, cobalt, cadmium); and chromium,
      which had a distinctive behavior.

PMID- 14708660
TI  - Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and
      enzymatic biomarkers.
AB  - The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has
      been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at
      12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers
      concerning growth rate, chlorophyll content and indicators of photosynthetic and
      antioxidant enzyme activities. The change of the 13 parameters showed a great
      variation of sensitivity indicating differences in parameters' suitability to be
      used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The
      order of sensitivity between those biomarkers was: Antenna size (ABS/RC) >
      Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield
      (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool
      (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching
      (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) >
      Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The
      effect of oxyfluorfen on the changes of those parameters was interpreted as a
      result of herbicide mode of action at molecular level of alga cellular system.
      This study indicated for some photosynthetic and enzymatic biomarkers to be
      useful indicators of toxicity effect induced in non-target alga species.
      Determination of biomarkers' sensitivity order may facilitate their selection to
      be used in environmental risk assessment of polluted water.

PMID- 14708661
TI  - Assessment of the probabilistic ecological risk assessment-toxic equivalent
      combination approach for evaluating pesticide mixture toxicity to zooplankton in
      outdoor microcosms.
AB  - The probabilistic ecological risk assessment-toxic equivalent (PERA-TE)
      combination approach was recently introduced in response to the increased demand
      for risk assessment approaches that can accommodate mixtures. The effectiveness
      and validity of the PERA-TE approach was assessed using two types of pesticide
      mixtures tested in outdoor microcosms. The first type of mixture consisted of
      pesticides with similar modes of action (the organophosphorus insecticides
      chlorpyrifos and diazinon) and the second of pesticides with different modes of
      action (chlorpyrifos, endosulfan, and trifluralin). To assess the toxicity of,
      and potential interaction within, each type of mixture, theoretically equitoxic
      TE mixtures were prepared in different proportional ratios. The TE mixtures were
      based on the 10th centile of acute toxicity effects distributions (data obtained
      from the literature) and a factor of the sum of the 90th centile field
      concentrations extrapolated from exposure distributions based on North American
      surface water monitoring data. Changes in zooplankton population abundances were
      used as the effect measure. The binary organophosphorus mixtures were equitoxic
      and conformed to the concentration addition model. The observed response trends
      of zooplankton exposed to the mixture of chemicals with different modes of action
      were a result of the susceptibility of individual taxa to the dominating
      pesticide in each mixture. Overall, the PERA-TE approach was not effective in
      predicting the toxicity and interaction of all mixture types and should be
      limited to assessing mixtures of chemicals with similar modes of action.

PMID- 14708662
TI  - Mercury toxicity in the aquatic oligochaete Sparganophilus pearsei. II: Autotomy
      as a novel form of protection.
AB  - Aquatic oligochaetes are commonly used for toxicity testing and for assessment of
      sediment impairment; some species can be relatively tolerant of sediment
      contaminants. However, there have been few studies of tolerance mechanisms; most
      work has focused on behavioral changes. The aquatic oligochaete worm,
      Sparganophilus pearsei, can be extremely tolerant to mercury in sediments
      depending on its prior history of exposure. Three S. pearsei populations,
      differing in their history of mercury exposure and in their tolerance to mercury,
      were assessed to determine tolerance mechanisms. In mercury-contaminated
      sediments, tolerant worms accumulated this contaminant in their caudal segments
      (i.e., their tails), which were then jettisoned via the process of autotomy, thus
      providing a mechanism of detoxification. This detoxification process appears to
      require a certain level of tolerance and may represent a novel exposure route for
      other organisms via feeding on discarded tails or release of accumulated
      contaminants as the tails decompose. Measurements of tissue mercury
      concentrations as contaminant body residues for this species (CBRs) are compared
      to other aquatic invertebrates.

PMID- 14708663
TI  - Accumulation and soluble binding of cadmium, copper, and zinc in the polychaete
      Hediste diversicolor from coastal sites with different trace metal
      bioavailabilities.
AB  - Bioaccumulation of cadmium, copper, and zinc was examined in common ragworms
      Hediste diversicolor from control (Bay of Somme, Blackwater) and metal-rich
      (Seine estuary, Boulogne harbor, Restronguet Creek) sites in France and the
      United Kingdom. The degree of exposure in the field was assessed by considering
      both total concentrations in superficial sediment and the quantities of metals
      which may be released in vitro at different pH levels. Among the three
      contaminated sites, release of the three metals was not detectable in Boulogne
      harbor, in correlation with limited enhancement of the metal concentrations in
      the common ragworms from this site. Even at those sites where zinc could be
      released in vitro from the sediment, zinc concentrations were not enhanced in
      common ragworms, in agreement with previous findings indicating that the body
      content of this metal is regulated in H. diversicolor. At all the studied sites,
      bioaccumulated zinc was mainly in cytosolic form. The distribution of cadmium and
      copper varied according to the origin of the common rag-worms, the insoluble
      fraction increasing with the degree of contamination (cadmium in the Restronguet
      Creek, copper in the Seine estuary, and even more in Restronguet Creek). In the
      cytosolic fraction, metals were partly linked to cytosolic heat-stable thiolic
      compounds (CHSTC) with molecular masses (5-6 kDa and about 12 kDa) consistent
      with metallothionein-like proteins (MTLP). Metal-binding to MTLP varied with the
      degree of contamination and with the metal studied. In contrast to many
      invertebrates, the presence of metal-binding CHSTC (MM about 2 kDa) other than
      MTLP seems to be a peculiar feature of H. diversicolor.

PMID- 14708664
TI  - The effects of pH and dissolved organic carbon on the toxicity of cadmium and
      copper to a freshwater bivalve: further support for the extended free ion
      activity model.
AB  - The extended free ion activity model (FIAM) was developed by integrating concepts
      from the original FIAM into biological receptor theory, to obtain a conceptual
      model that more precisely quantifies the interaction of chemical species at
      biological receptor sites. The extended FIAM was tested by determining the acute
      (48 h) valve movement behavior (VMB) (measured in terms of the duration of valve
      opening) of the Australian freshwater bivalve, Hyridella depressa, to increasing
      concentrations of total Cd or Cu, in a standard synthetic water under conditions
      of varying pH (6.5-7.5) and/or dissolved organic carbon (as model fulvic acid
      (FA)) concentrations (0-11.2 mg L(-1)). Valve movement behavior, measured using
      an automated data acquisition system, was shown to be a quantifiable and rapid,
      real-time endpoint for assessing the toxic effects of Cd and Cu exposures. The
      VMB of H. depressa to Cd was independent (p > 0.05) of pH and/or model FA
      concentration. In contrast, the VMB of H. depressa to Cu was highly dependent (p
      < 0.001) on pH and/or model FA concentration; individuals were more sensitive to
      Cu at low pH and model FA concentrations. The VMB of H. depressa was directly
      proportional to the activity of the free metal ion (Cd2+), for the linear region
      of the concentration-response curves. In contrast, the VMB of H. depressa was a
      weighted function of the activities of the free metal ion and the 1:1 metal
      hydroxide species (i.e. 2.02 x Cu2+ + CuOH+), whereby Cu2+ had a two-fold greater
      binding affinity than CuOH+ at the cell membrane surface. Moreover, the results
      for Cd and Cu are consistent with the extended FIAM, as opposed to the original
      FIAM, where the result for Cu would be regarded as an exception. The extended
      FIAM explained 98% of the variability in VMB, whereas the original FIAM explained
      only 63% (i.e. an improvement of 35%). The improved predictability of organism
      response to Cu is relevant to advancing water quality guidelines for protecting
      aquatic biota.

PMID- 14708665
TI  - Causes of sediment toxicity to Mytilus galloprovincialis in San Francisco Bay,
      California.
AB  - Since the San Francisco Regional Monitoring Program (RMP) sampling began,
      elutriate samples prepared with sediment from the Grizzly Bay monitoring station
      have been consistently toxic to bivalve larvae (Mytilus galloprovincialis). An
      investigation into the cause of toxicity was initiated with a Phase I Toxicity
      Identification Evaluation (TIE) using bivalve embryos. TIE results and chemical
      analyses of elutriate samples suggested that divalent metals were responsible for
      the observed toxicity. Following the initial characterization of trace metals as
      toxicants, additional TIEs were performed on elutriates prepared from three
      additional Grizzly Bay samples collected between 1997 and 2001. Additional TIEs
      included ethylenediamine tetraacetic acid (EDTA) treatments in a sediment-water
      interface (SWI) exposure system, and the use of a cation exchange column with
      serial elution of sample fractions with hydrochloric acid of increasing
      normality. EDTA significantly reduced toxicity in overlying water in the SWI
      system. The cation exchange column reduced both toxicity and concentrations of
      trace metals, and serial elution of the column added back both toxicity and
      specific metals contained in individual acid fractions. Chemical analyses of
      three elutriate samples demonstrated copper concentrations were within the range
      toxic to bivalves. Results of Phase I TIEs, additional Phase II treatments, SWI
      exposures, and metals analyses indicate the potential for metal toxicity in
      sediments from this estuarine site. When combined with the results of standard
      TIE methods, a solid-phase cation extraction and elution approach identified
      copper as the most probable cause of toxicity.

PMID- 14708667
TI  - Bioavailability and toxicity of freshly neutralized aluminium to the freshwater
      crayfish Pacifastacus leniusculus.
AB  - Freshly neutralized aluminium (Al) is toxic to a variety of freshwater organisms
      despite its insolubility at circumneutral pH. Insoluble Al acts exogenously--for
      example, on the fish gill--thereby impairing respiratory function, and
      endogenously in grazing and filter-feeding invertebrates following ingestion
      during drinking and feeding. This paper examines the bioavailability and
      behavioral toxicity of freshly neutralized Al to the freshwater crayfish
      Pacifastacus leniusculus exposed to 500 microg L(-1) added Al for 20 days under
      controlled conditions. We test the hypothesis that aqueous Al is toxic to the
      crayfish and that this is largely due to the metal's association with the gill
      rather than following accumulation in the body. Little Al was accumulated in the
      digestive gland (hepatopancreas) or flexor muscle, but large amounts were
      associated with the gills, resulting in concentration factors of up to 1 x 10(4).
      Histochemistry showed that much of this metal was extracellular to the gill
      epithelium and associated with the mucus layer. Behavioral dysfunction was
      observed following exposure to Al for five days. Reduction in the amount of Al in
      the water column, due to binding to snail trail mucus attached to the substrate,
      reduced the amount of Al associated with the gill and delayed the onset of
      behavioral dysfunction. We conclude that freshly neutralized Al is toxic to the
      crayfish and that main site of Al action is the gill.

PMID- 14708666
TI  - Bioconcentration and biomagnification of mercury and methylmercury in North Sea
      and Scheldt estuary fish.
AB  - Total Hg and MMHg concentrations were assessed in more than 350 fish and
      shellfish samples. Hg concentrations in Greater North Sea fish of prey range from
      0.039 mg kg(-1) wet weight (ww; for ray) to 0.61 mg kg(-1) ww (for dogfish) and
      for all other fish species, from 0.045 mg kg(-1) ww (for plaice) to 0.33 mg kg(
      1) ww (for sand sole), with 95 +/- 2% of the Hg content in the MMHg form. In
      Belgian coastal zone, fish concentrations range from 0.063 mg kg(-1) ww for
      plaice to 0.13 mg kg(-1) ww for flounder, with 82-87% of the Hg content in the
      MMHg form. In fish of the Scheldt, which is a very polluted estuary, Hg levels,
      as well as the percent MMHg of the total Hg, were lower than in the two zones
      previously mentioned. The intraspecies variability is of the order of 50% in each
      of the three zones. In liver tissue, a much larger variability was observed than
      in muscle tissue, except for fish species of the Scheldt. In most cases, the MMHg
      fraction in a particular fish species is inversely related to the intraspecies
      variability. Bioconcentration and biomagnification factors (BCF and BMF,
      respectively) were assessed. MMHg-BMFs were a few orders of magnitude higher than
      Hg(inorganic)-BMFs, and for the same species were always highest in the Greater
      North Sea and lowest in the Scheldt. For each of the Belgian coastal zone four
      species, a weak positive correlation between Hg content and fish length was
      found; however, the larger the size-range, the better the correlation. Taking
      fish length into account, a statistically significant difference in contamination
      level was observed for species sampled from the different geographical zones.

PMID- 14708668
TI  - Chemobehavioral changes induced by short-term exposures to prochloraz,
      nicosulfuron, and carbofuran in goldfish.
AB  - The behavioral effects of short periods (2, 4, 6, 8 h) of static exposure to
      prochloraz (imidazole fungicide) and nicosulfuron (sulfonylurea herbicide) were
      recorded in goldfish (Carassius auratus). Observations were also made in an
      olfactometer to assess the effects of 8-h exposures to these two pesticides and
      to carbofuran (carbamate insecticide) on the behavioral responses to the flow of
      a solution of four L-amino acids (glycine, alanine, valine, taurine), mixed in
      the same relative proportions as in the urine of conspecifics. Each pesticide was
      tested at three sublethal concentrations (25, 50, 100 microg/L), and the
      behaviors recorded were related to swimming pattern, social interactions, and
      comfort movements. Static exposures to prochloraz affected horizontal
      displacements, burst swimming, grouping, and buccal movements. Static exposures
      to nicosulfuron affected burst swimming and grouping. In pesticide-unexposed fish
      (control), the flow of the amino acid solution induced attraction, decreased
      sheltering, and increased horizontal displacements, burst swimming, buccal
      movements, and antagonistic interactions. Compared to the controls, some of the
      behavioral responses to the solution of amino acids were significantly different
      after 8 h of subacute exposure to prochloraz and carbofuran. Both pesticides
      decreased attraction and increased sheltering. In addition, carbofuran decreased
      buccal movements and antagonistic interactions. Contrastingly, exposure to
      nicosulfuron showed no significant effect. This study further confirms the great
      vulnerability of fish behavior and chemocommunication processes to exposure to
      waterborne pesticides.

PMID- 14708669
TI  - Impacts from PCB accumulation on amphibians inhabiting streams flowing from the
      Paducah Gaseous Diffusion Plant.
AB  - Contamination at the Paducah Gaseous Diffusion Plant (PGDP), Paducah, Kentucky,
      has been under evaluation for many years. We studied amphibians in selected
      outfalls (drainage ditches) flowing from the PGDP to determine if PCBs were
      accumulating in their tissues and how this might affect local populations. We
      determined relative amphibian species richness and abundance among seven outfalls
      and three reference streams by listening to their calls during audio surveys. We
      also captured amphibians from each study site during the summers of 2000 and 2001
      and analyzed their carcasses for PCBs (Aroclor 1260 and 34 congeners) and livers
      for ethoxyresorufin O-deethylase (EROD) activity, a biomarker of PCBs and other
      organic contamination. Ten species were heard across study sites, and abundance
      and richness at outfalls were similar to those observed at reference sites.
      However, there were significant differences in abundance (p = 0.001) and richness
      (p = 0.048) of amphibians between continuously flowing and intermittent outfalls.
      There were no significant differences in PCB concentrations (p = 0.113) in
      amphibians captured from study sites, although Aroclor 1260 concentrations tended
      to be higher in amphibians collected from one outfall (outfall 12) on the east
      side of the plant (x = 1260 microg/kg) compared with all other study sites (x =
      489 microg/kg). EROD activity measured in the liver was not indicative of Aroclor
      1260 concentrations in amphibians at the PGDP, and EROD did not differ by study
      site, species, age class, or gender. PCB concentrations measured in amphibians at
      the PGDP were similar to concentrations measured at reference sites and did not
      appear to negatively affect individual amphibians or abundance and richness.

PMID- 14708670
TI  - Oxidative stress in laboratory-incubated double-crested cormorant eggs collected
      from the Great Lakes.
AB  - Double-crested cormorant (Phalacrocorax auritus) eggs were collected in 1998 from
      three sites on Lakes Huron and Superior and either analyzed for 2, 3, 7, 8
      tetrachlorodibenzo-p-dioxin (TCDD)-like residues or artifically incubated. Some
      of the incubated eggs were injected with vitamin E (antioxidant) or piperonyl
      butoxide (CYPIA blocker) to examine the role of CYPIA and oxidative stress in
      normal bird development. Embryos (day 23) were analyzed for hepatic
      ethoxyresorufin O-deethylase (EROD) activity and different measures of oxidative
      stress. Glutathione-related parameters were also measured in brain. In contrast
      to the historical data, there were no statistically significant differences in
      concentrations of chlorinated dioxins, furans, dioxin-like PCBs, or total TCDD
      equivalents (TEQs) in eggs among sites. Survival and incidence of abnormalities
      were comparable at all study sites. Slight differences in liver, heart, and egg
      weight were observed among sites. A greater incidence of eye deformities was
      observed in embryos treated with vitamin E. Treatment with the CYPIA blocker,
      piperonyl butoxide, decreased the body weights of embryos. EROD activities were
      similar at all locations, but measures of oxidative stress varied among
      locations. There were greater levels of oxidized glutathione and oxidative DNA
      damage at Little Charity Island in Saginaw Bay. There was relatively great
      interindividual variation in biochemical responses and significant interrelation
      of the parameters of oxidative stress. While exposure to PCDD/DF and PCBs does
      not seem to explain the observed oxidative stress, the potential of these
      compounds to cause the observed effects can not be completely excluded.

PMID- 14708671
TI  - Congener-specific patterns and toxic assessment of polychlorinated biphenyls in
      resident and migratory birds from Southern India and Lake Baikal in Russia.
AB  - Concentrations of polychlorinated biphenyls (PCBs), including non-, mono-, and di
      ortho congeners, were determined in migratory and resident birds collected from
      India and Lake Baikal in Russia. In the 11 different species examined, total PCBs
      concentrations were in the range of 11-4500 ng/g (wet wt). IUPAC 105, 118, 138,
      153, and 180 were the predominant congeners in almost all the birds. White
      cheeked tern collected from India and common tern collected from Lake Baikal
      showed high PCBs concentrations of 4400 ng/g (wet wt) and 4500 ng/g (wet wt),
      respectively, and accumulated relatively high ratios of penta-CBs (IUPAC 118,
      105, 99). Toxic equivalents (TEQs) of non- and mono-ortho PCB congeners in birds
      collected from India and Lake Baikal were in the range of 1.5-56 and 2.8-370 pg/g
      wet wt, respectively. Toxic assessment results led by calculated TEQs of the
      transfer to eggs from female birds revealed that TEQs in most of migratory and
      resident birds were comparable to the lowest observable effect level (LOAEL) of
      chicken which is a highly sensitive species against dioxin-like compounds.
      Calculated transfer TEQs to eggs of common tern collected from Lake Baikal in
      autumn, however, exceeded the LOAEL of CYP1A induction in bald eagle embryos and
      ED50 of that in pheasant embryos, suggesting that embryo toxicity by coplanar
      PCBs in some avian species breeding in Lake Baikal is possible.

PMID- 14708672
TI  - Mercury residues in livers of bald eagles (Haliaeetus leucocephalus) found dead
      or dying in British Columbia, Canada (1987-1994).
AB  - Postmortem examinations were conducted on 82 bald eagles (Haliaeetus
      leucocephalus) found dead or dying in British Columbia, Canada, from 1987 to
      1994. As part of the examination, livers were analyzed for total mercury (Hg)
      content, as well as methylmercury (meHg) and selenium (Se) in selected
      individuals. In total, 67 eagles were classed as having low Hg exposure [total Hg
      liver residues ranging from 0.5 to 17.2 mg/kg dry weight (dw)]. Fourteen eagles
      were moderately exposed (liver residues ranging from 19.2 to 36.8 mg/kg Hg dw).
      One eagle was judged to have died of Hg poisoning, with a total liver Hg content
      of 130.3 mg/kg dw, of which approximately 77% was meHg. The poisoned eagle and
      most of the exposed eagles were found in locations where effluent from pulp and
      paper processing plants is discharged along the British Columbia coast. In total,
      6% of eagles examined died as a result of acute metal toxicosis (one from Hg
      poisoning, four from lead poisoning), in comparison to 72% dying from trauma
      (electrocution, vehicle/power line collision, eagle attack, trap, gunshot,
      drowning, and asphyxiation) and 11% from disease. The cause of death was
      undetermined in the remaining 11% of eagles.

PMID- 14708673
TI  - EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002
      Geneva, Switzerland. Consensus statement (long version).

PMID- 14708674
TI  - Clinical virology of hepatitis B virus infection.

PMID- 14708676
TI  - Immunopathogenesis of hepatitis B.

PMID- 14708675
TI  - Hepatitis B virus (HBV) DNA assays (methods and practical use) and viral
      kinetics.

PMID- 14708677
TI  - Liver tissue examination.

PMID- 14708678
TI  - Natural history of hepatitis B.

PMID- 14708679
TI  - Hepatitis B virus and hepatocellular carcinoma.

PMID- 14708680
TI  - Epidemiology of hepatitis B in Europe and worldwide.

PMID- 14708681
TI  - Hepatitis B vaccines.
AB  - Yeast-derived hepatitis B vaccines, containing the small HBV envelope protein
      SHBAg, are immunogenic, safe and cost-effective in prevention of hepatitis B
      virus infection in neonates, children and adults. Newly developed pre-S/S
      hepatitis B vaccines may play a role in inducing fast and augmented
      seroconversion rates in special risk groups.

PMID- 14708682
TI  - Impact of hepatitis B immunization, Europe and worldwide.

PMID- 14708683
TI  - Safety of immunization and adverse events following vaccination against hepatitis
      B.

PMID- 14708684
TI  - Health care workers and hepatitis B.

PMID- 14708685
TI  - Mechanisms of action of interferon and nucleoside analogues.

PMID- 14708686
TI  - Interferon-alpha for HBeAg-positive chronic hepatitis B.

PMID- 14708687
TI  - Results of lamivudine therapy for HBe antigen positive hepatitis (in the West).

PMID- 14708688
TI  - Results of lamivudine trials in Asia.
AB  - In summary, 100 mg daily lamivudine therapy is safe and effective in Asian
      patients in terms of HBV suppression, ALT normalization and improvement in
      histology. The complete response rate after 1 year of lamivudine therapy is only
      around 15% but increases with increasing duration of treatment and increasing
      pretherapy ALT levels. Similar results were observed in patients with HBeAg
      negative chronic hepatitis but published data are limited. YMDD mutations may
      emerge after 6-9 months of lamivudine therapy and its incidence also increases
      with increasing duration of therapy. The emergence of YMDD mutations is
      associated with viral and biochemical breakthrough. Hepatitis flares, sometimes
      associated with hepatic decompensation, may develop after stopping lamivudine
      therapy and in patients with YMDD mutations during continuing lamivudine therapy.
      The benefit of long-term lamivudine therapy therefore must be weighed carefully
      against the concern about YMDD mutations and the durability of therapeutic
      response. The development of new strategies, including selection of patient and
      timing of therapy, and new drugs are needed to further improve the therapeutic
      efficacy.

PMID- 14708689
TI  - Adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B: a
      review of the major clinical studies.

PMID- 14708690
TI  - Hepatitis B viral resistance: mechanisms and diagnosis.

PMID- 14708691
TI  - Hepatitis B virus resistance to antivirals: clinical implications and management.

PMID- 14708692
TI  - Entecavir, FTC, L-FMAU, LdT and others.
AB  - To summarize, the future of chronic hepatitis B therapy seems to be the
      combination of different drugs. Ideally, the optimal drugs to combine would meet
      the following criteria: they should be orally applicable, they should have an
      excellent safety profile and the duration of therapy should limited. Currently,
      the drugs most likely to fulfill these criteria are the nucleoside analogs.

PMID- 14708693
TI  - The treatment of hepatitis B e antigen-positive chronic hepatitis B with
      pegylated interferon.

PMID- 14708694
TI  - Combination therapy for chronic hepatitis B.

PMID- 14708695
TI  - Immunomodulatory drugs and therapeutic vaccine in chronic hepatitis B infection.

PMID- 14708696
TI  - Chronic hepatitis B e antigen (HBeAg) negative, anti-HBe positive hepatitis B: an
      overview.

PMID- 14708697
TI  - Treatment of HBeAg-negative chronic hepatitis B with interferon or pegylated
      interferon.

PMID- 14708698
TI  - Treatment of hepatitis B e antigen-negative chronic hepatitis B with lamivudine.

PMID- 14708699
TI  - Treatment of HBeAg negative chronic hepatitis B with new drugs (adefovir and
      others).

PMID- 14708700
TI  - Management of the patient with hepatitis B virus-related cirrhosis.

PMID- 14708701
TI  - Liver transplantation for hepatitis B virus-related liver disease: indications,
      prevention of recurrence and results.

PMID- 14708702
TI  - Treatment of recurrence of hepatitis B in transplant patients.

PMID- 14708703
TI  - Treatment of chronic hepatitis B virus infection in patients co-infected with
      human immunodeficiency virus.

PMID- 14708704
TI  - Treatment of chronic hepatitis B in children.

PMID- 14708705
TI  - Treatment of hepatitis B in special patient groups: hemodialysis, heart and renal
      transplant, fulminant hepatitis, hepatitis B virus reactivation.

PMID- 14708706
TI  - Delta hepatitis: an update.

PMID- 14708707
TI  - Perspectives on therapy of hepatitis B.

PMID- 14708708
TI  - Perspectives of public health: present and foreseen impact of vaccination on the
      epidemiology of hepatitis B.

PMID- 14708709
TI  - Challenges in therapy of chronic hepatitis B.

PMID- 14708710
TI  - Progress of HLA-G in cancer.

PMID- 14708711
TI  - HLA-G modulates immune responses by diverse receptor interactions.
AB  - HLA-G regulates immune responses as it binds different receptors expressed on
      natural killer (NK) cells, T cells and myeloid cells. HLA-G1 can inhibit NK- and
      T-cell-mediated lysis of target cells by its interaction with the inhibitory
      receptors ILT2 and ILT4. Engaging KIR2DL4 triggers different reactions depending
      on the activation state of the effector cells. The indirect recognition of HLA-G
      as peptide presented by HLA-E and recognized by the CD94/NKG2 receptor family
      might further power the battle between the immune system and tumor cells.
      Secreted HLA-G5 can also bind CD8 and induces Fas/Fas ligand-mediated apoptosis
      in activated CD8+ lymphocytes.

PMID- 14708712
TI  - HLA-G in cancer: a way to turn off the immune system.
AB  - The expression of HLA-G in cancer represents a strategy employed by tumors to
      avoid immune destruction. Indeed, this non-classical HLA class I molecule
      suppresses various immune cell functions through binding to inhibitory receptors.
      We here review the studies done by our group that described for the first time
      (i) HLA-G expression in malignancies such as melanomas, renal and breast
      carcinomas. (ii) the up-regulation of HLA-G gene transcription by tumor
      environmental factors such as cytokines and stress and by agents used in
      chemotherapy such as demethylating molecules, and (iii) the biological relevance
      of such HLA-G expression in the evasion of malignant cells from antitumor immune
      response.

PMID- 14708713
TI  - HLA-G and IL-10 expression in human cancer--different stories with the same
      message.
AB  - Immune evasion in cancer may result from structural and functional alterations of
      human leukocyte antigen (HLA) class I molecules and/or local release of
      immunosuppressive cytokines, such as interleukin (IL)-10. In lung cancer, both of
      these mechanisms seem to often take place, resulting in the impaired tumor
      recognition and the progression of the disease. In primary cutaneous lymphomas on
      the other side, the shift towards immunosuppressive T helper (Th)2 cytokine
      profile and the secretion of IL-10 appears to occur more frequently than the loss
      of HLA class I molecules. In addition to down-regulation of HLA class I
      expression, IL-IO appears to be one of the factors responsible for the up
      regulation of HLA-G, another molecule involved in the immunescape. It is possible
      that the expression of HLA-G itself may account for induction of Th2-skewing
      state and the production of IL-10, thence establishing a vicious circle of immune
      abrogation in cancer. This article reviews the current literature on this topic
      and provides new insights into the role of HLA-G and IL-10 in cancer.

PMID- 14708714
TI  - Hide-and-seek in the brain: a role for HLA-G mediating immune privilege for
      glioma cells.
AB  - This review summarizes the current knowledge on the expression and functional
      role of HLA-G in normal CNS cells and brain tumor cells in vitro and in vivo. The
      CNS has classically been viewed as an immune-privileged organ. Here we discuss
      some of the particularities of anti-tumoral responses within this compartment.
      Special emphasis is dedicated to the possible role of the non-classical MHC
      molecule HLA-G as an alternative mechanism of immune escape. We review the
      mechanisms how glioma cell-derived HLA-G may paralyze the immune system and which
      cellular subsets of the immune system are affected. Possible therapeutic
      implications derived from these observations include the targeting of HLA-G
      expression within the framework of inducing glioma-specific immunity.

PMID- 14708715
TI  - The role of HLA-G for protection of human renal cell-carcinoma cells from immune
      mediated lysis: implications for immunotherapies.
AB  - HLA-G as a non-classical MHC class I molecule exhibits a limited tissue
      distribution and exerts multiple immune regulatory functions including the
      induction of immune tolerance. In addition, HLA-G has been detected in some
      tumors of different histology and therefore may represent a novel immune escape
      mechanism of tumor cells. Despite the immunogenicity of renal cell carcinoma
      (RCC), outgrowth of tumor cells occurs which might be attributable to abrogation
      of efficient anti-tumor responses. We here review the potential role of HLA-G in
      RCC immunology, the HLA-G expression pattern and its functional consequences on
      immune responses. A heterogenous constitutive and interferon-gamma inducible HLA
      G mRNA and protein expression was found in RCC cell lines and tumor lesions, but
      not in autologous normal kidney epithelium. HLA-G transcription and protein
      expression was detected at a high frequency in primary RCC lesions and RCC cell
      lines. Functional studies performed with alloreactive natural and lymphokine
      activated killer cells as well as antigen-specific CD8+ T cell populations
      demonstrated that HLA-G expression inhibits lysis of RCC cells by these different
      immune effector cells, whereas HLA-G- normal kidney cells were recognized. Thus,
      aberrant HLA-G expression might participate in evasion of these tumor cells from
      immunosurveillance.

PMID- 14708716
TI  - HLA-G in melanoma: can the current controversies be solved?
AB  - The potential role of HLA-G in tumor immune escape has stimulated interest in the
      analysis of HLA-G antigens in malignant cells. Malignant melanoma is the tumor
      which has been mostly analyzed for HLA-G expression. Results obtained by seven
      groups of investigators about HLA-G expression in 108 melanoma cell lines have
      been concordant. HLA-G mRNA has been found in about 50% of the cell lines tested,
      whereas HLA-G protein has been found in less than 1% of the cell lines analyzed.
      In contrast, results obtained from six groups of investigators about HLA-G
      protein expression in 133 melanoma lesions have been conflicting. The possible
      causes of these conflicting results as well as the reasons for the discrepancy in
      HLA-G expression between cultured melanoma cell lines and surgically removed
      lesions have been discussed. Lastly, data about the potential clinical relevance
      of HLA-G expression in melanoma has been reviewed. The available data in the
      literature strongly suggest that progress in this exciting research area would
      greatly benefit from experiments to solve the current controversies in the field.

PMID- 14708717
TI  - Secretion of sHLA-G molecules in malignancies.
AB  - Our clinical studies revealed significantly increased soluble HLA-G (sHLA-G)
      plasma levels in patients suffering from malignant melanoma, glioma, breast and
      ovarian cancer. Specific ELISpot assays demonstrate that sHLA-G molecules
      expressing intron-4 sequences are preferentially secreted by peripheral blood
      monocytes. In vitro, the sHLA-G secretion of monocytes and tumor cells was
      strongly enhanced by TH1 cytokines like IFN-alpha, -beta, -gamma whereas TH2
      cytokines (e.g. IL-4, -10) had minor effects. As sHLA-G can inhibit the functions
      of T and NK cells high concentration of these molecules should systemically or at
      the tumor side reduce the immune surveillance and thus favour the progression of
      cancer.

PMID- 14708718
TI  - HLA-G and lymphoproliferative disorders.
AB  - The immunomodulatory properties of the HLA-G molecule explain its relevance in
      malignancies. Our investigations in lymphoproliferative disorders show (i) a
      frequent and variable distribution of alternatively spliced HLA-G mRNA isoforms,
      (ii) a rare cell surface expression in diffuse large cell lymphomas with HLA
      class I loss in half of cases, and (iii) an increased serum level of sHLA-G in
      half of cases. The potential role of the microenvironment and/or tumoral process
      in HLA-G expression is discussed in the light of these data. HLA-G rather through
      its soluble isoform might provide a new way of immune evasion for lymphoid
      proliferations.

PMID- 14708719
TI  - The "ultra" years and many more to come: a glimpse into the future.

PMID- 14708720
TI  - Genome, proteome, and metabolome: where are we going?
AB  - Rapid advances have been made in recent years in understanding the genetic makeup
      of mankind. The human genome project has identified approximately 32,000 genes
      that occur in humans. It is now possible to perform genetic profiling with many
      of the genes to understand embryogenesis, growth and development, the normal
      state, senescence, diseases, and tumorogenesis. Techniques in molecular
      diagnostics are becoming available that will expand the ability to provide more
      precise diagnoses, predict response to treatment, evaluate treatment, and predict
      prognosis and outcome. Genetic profiling will, in the future, direct therapy by
      providing specific targets for development of medications, antibodies, and gene
      therapy. More recently, the attention of the scientific community has turned
      toward the gene products within the cell and tissue matrix, namely proteins. The
      field of proteomics is an evolving area, which may shed light on the proteins
      associated with diseases and tumors. This will again provide a mechanism for
      creating personalized, designer therapies for individual patients or groups of
      patients with similar diseases based on expression profiling. The final avenue of
      exploration in understanding cell function is the metabolites that occur as the
      end products of cellular function (metabolome). These metabolites, or improper
      degradation of cellular proteins, may lead to disease and neoplasia. The role of
      the pathologist in expression profiling for diseases and tumorigenesis is of
      considerable importance in providing diagnostic information and predicting
      outcome based on pathobiologic features of diseases and tumors.

PMID- 14708721
TI  - Organized deposits in the kidney and look-alikes.
AB  - Organized or structured deposits are encountered during electron microscopic
      examination of kidney tissue in a wide variety of primary renal and multisystemic
      disorders. They are most commonly seen in the renal glomerulus, though
      extraglomerular sites are occasionally involved. In some cases, organized
      deposits herald the presence of a specific disease process. Included in this
      category are organized substances containing immunoglobulin molecules or parts
      thereof as well as non-immunoglobulin-containing materials that accumulate in
      several rare heritable disorders. A second broad category of structured deposits
      includes substances that accumulate in response to nonspecific tissue injuries.
      In many instances, such "look-alikes" can be difficult to distinguish from
      disease-specific structured deposits. Ultrastructural pathology is central to the
      detection and characterization of organized deposits in the kidney and is the
      primary focus of this paper. Correlative light microscopic studies are often
      useful, however, and will be described as well.

PMID- 14708722
TI  - Lipid deposits and lipo-mucosomes in human cholecystitis and epithelial
      metaplasia in chronic cholecystitis.
AB  - Among the inflammatory changes seen in cholecystitis, the ultrastructural
      alterations of the human gallbladder epithelium include lipid and lipofuscin
      deposits, fusions of lipid deposits and mucus-containing vesicles forming complex
      substructural formations called lipo-mucosomes, and microvillar changes of sparse
      microvilli and basal bodies. Small, lipid-laden structures, such as VLDL-like
      vesicles, also are fused with the mucus vesicles. Epithelial cell sloughing could
      liberate and add lipo-mucosomes to the biliary sludge and participate in
      gallstone formation. With chronic cholelithiasis, fatty degeneration of scattered
      epithelial cells appears to alter the epithelial lining and favors metaplastic
      change that could lead to other pathologic changes, including carcinoma in situ
      like lesions. In addition to lipid deposition in macrophages, lipid is also
      incorporated in other cells and tissues of the gallbladder wall (endothelium of
      capillaries, smooth muscles and fibrocytes).

PMID- 14708723
TI  - Inspissation of pancreatic zymogen material in cystic fibrosis.
AB  - Cystic fibrosis is characterized by the elaboration of abnormal, thick, tenacious
      mucus resulting in obstructive disease in sites such as the lung and pancreas. In
      the pancreas, acinar plugs of mucus have been reported as the earliest
      recognizable morphologic lesion in cystic fibrosis. Since mucus is not normally
      elaborated within the pancreatic lobular tissue, the mechanism of accumulation of
      mucus in acini is enigmatic. To investigate this phenomenon, well-preserved
      autopsy pancreatic tissue was studied ultrastructurally. This study demonstrated
      very prominent mucous metaplasia in these diseased organs. Acinar plugs, though,
      developed before mucous metaplasia. Subsequent histochemical study was performed,
      which demonstrated that the early acinar plugs exhibited the same staining
      properties as zymogen granules and were distinct from the staining pattern of
      mucus in pancreatic tissue of cystic fibrosis patients. These findings, then,
      indicate that zymogen material, not mucus, becomes inspissated in the acini of
      the pancreas in early cystic fibrosis, and that subsequent mucous metaplasia
      occurs as the obstruction and exocrine atrophy progress.

PMID- 14708724
TI  - Microvillous inclusion disease with abundant vermiform, electron-lucent vesicles.
AB  - A 3-month-old girl with congenital secretory diarrhea underwent a duodenal
      biopsy. Histologic study showed villous atrophy and large amounts of PAS-positive
      material within enterocyte cytoplasm. Despite a clinical suspicion of
      microvillous inclusion disease, 2 sessions of electron microscopy were
      unsuccessful in detecting the diagnostic inclusions. Instead, large aggregates of
      electron-lucent, vermiform membranous vesicles were observed in enterocyte
      cytoplasm, corresponding to the PAS-positive material. A third attempt at
      electron microscopy was successful in detecting small numbers of microvillous
      inclusions. These and other recently reported cases document an expanding
      spectrum of ultrastructural findings in this disease, including examples where
      the classic microvillous inclusions are overshadowed by other features.

PMID- 14708725
TI  - Fibrillary noncongophilic renal and extrarenal deposits: a report on 10 cases.
AB  - Cases in which glomerular deposits of Congo red negative amyloid-like fibrils
      were demonstrated by electron microscopic identification are included in this
      study. In the 1,266 kidney biopsies studied, there were 9 biopsies from 8
      patients with fibrillary glomerulonephritis and 2 biopsies from 2 patients with
      systemic lupus In 1 case of fibrillary glomerulonephritis (FGN), autopsy was
      performed. Electron microscopic examination showed glomerular (100%) and
      extraglomerular (60%) fibrillary deposits in the biopsy samples of patients with
      FGN and also in patients with systemic lupus. In the autopsy case similar
      fibrillary deposits were demonstrated in the kidney, pancreas, spleen, lungs, and
      liver. The diameter of the fibrils, which were arranged similarly in all cases,
      varied from 8 to 27 nm individually, the length being about 1.5 microm. The
      authors speculate that extraglomerular kidney fibrillary deposits concurrent with
      the same type of deposits in other organs suggests systemic manifestation of FGN.

PMID- 14708726
TI  - Hyalinizing spindle cell tumor with giant rosettes and low-grade fibromyxoid
      sarcoma: an immunohistochemical and ultrastructural comparative investigation.
AB  - Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade
      fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several
      clinicopathologic features. This study compares the light microscopic,
      immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3
      of LG FMS to determine the degree of overlap of these 2 tumors. HSCTGR were
      composed of bland spindle cells within hyalinized to myxoid stroma. Scattered
      throughout the lesions were characteristic rosette-like structures, formed by a
      central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted
      of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells
      arranged in a swirling, whorled growth pattern. Immunohistochemical analysis
      showed diffuse positivity for vimentin in all cases, while few scattered tumor
      cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix
      showed intense positivity for type IV collagen, laminin, and fibronectin, with
      the exception of myxoid areas of LGFMS and the central core of the giant rosettes
      in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the
      features of fibroblasts, embedded in a collagenous stroma with irregular deposits
      of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share
      similar immunophenotypic and ultrastructural features, and together with other
      fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute
      a subset of fibrosarcomas formed by fibroblasts capable of producing large
      amounts of basal lamina-like material.

PMID- 14708727
TI  - Nail-patella glomerulopathy without associated constitutional abnormalities.
AB  - A 17-year-old boy presented with a history of longstanding hematuria and non
      nephrotic proteinuria without renal insufficiency, for which renal biopsy was
      performed. The findings by routine light microscopy and direct immunofluorescence
      study were mild and nonspecific. Electron microscopy, however, demonstrated the
      unexpected finding of distinct collagen fibrils within capillary wall basement
      membranes, typical of the nail-patella syndrome. Repeat physical examination
      following the biopsy confirmed the presence of normal nails and patellae, and
      radiographs of the knees were also normal. The boy's renal disease was stable at
      last follow-up. The authors briefly discuss the differential diagnosis, and
      suggest that this case represents an unusual manifestation of the nail-patella
      syndrome, in which the glomerular changes are present in the absence of the usual
      associated constitutional abnormalities.

PMID- 14708728
TI  - Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a case
      report with fine-needle aspiration biopsy, histopathology, electron microscopy,
      and cytogenetics.
AB  - Although extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma,
      its morphological, ultrastructural, and cytogenetical features have been well
      investigated. The authors describe a very rare variant of EMC with neuroendocrine
      differentiation. A 49-year-old woman presented with an 11-cm, deep-seated,
      lobulated soft tissue mass in the left thigh and a lymph node metastasis in the
      left groin. Analysis of fine-needle aspiration biopsy (FNAB) smears and a
      cellblock prepared from FNAB material, as well as histological sections of the
      excised tumor, showed a neoplasm composed of rounded and elongated cells arranged
      in strands and cords in a myxoid background matrix. The nuclei were rounded and
      often eccentric. The immunohistochemical phenotype was S-100 protein -, neuron
      specific enolase +, and chromogranin A+. Electron microscopy showed tumor cells
      harboring numerous mitochondria, partial basal lamina, and unequivocal
      neuroendocrine granules. Molecular genetic analysis revealed a TAF15/NR4A3
      fusion, a characteristic rearrangement occurring in about 25% of cytogenetically
      investigated EMC. A few cases of EMC with neuroendocrine differentiation have
      been reported. However, the only previously described case with genetic
      information also displayed the t(9;17) instead of the more common t(9;22),
      suggesting an association between type of primary chromosome abnormality and
      neuroendocrine differentiation.

PMID- 14708729
TI  - Hepatoblastoma in a 15-month-old male: cytomorphology, electron microscopy, and
      differential diagnosis.
AB  - The authors describe a case of hepatoblastoma in a 15-month-old male and discuss
      the differential diagnosis and electron microscopic features of small round cell
      tumors. The patient was found to have an enlarged liver and was admitted to the
      hospital for further investigation. Fine-needle aspiration of the liver revealed
      small. uniform cells with increased nuclear/cytoplasmic ratio and focal rosette
      formation. A diagnosis of small blue cell neoplasm favoring hepatoblastoma was
      made, but neuroblastoma could not be ruled out. Electron microscopic analysis
      performed on the liver aspirate showed features of hepatic differentiation as
      well as absence of neuroblastic differentiation. The diagnosis of hepatoblastoma
      was made. Serum alpha-fetoprotein level of 33,250 mg/L confirmed the diagnosis.
      Liver biopsy performed subsequently showed tumor cells arranged in nests, acini,
      and trabeculae with mitotic figures. Electron microscopy showed the same findings
      as described above. The patient underwent chemotherapy for 4 months and
      subsequently a partial liver resection was performed. This case illustrates the
      important role of electron microscopy in evaluating small round cell tumors in
      children.

PMID- 14708730
TI  - Calibers and calipers: phenotypes, phenomes, and the pediatric pathologist.

PMID- 14708731
TI  - Gastrointestinal polyposis in childhood: clinicopathologic and genetic features.
AB  - Gastrointestinal polyps and certain extraintestinal lesions in children may
      herald a hereditary polyposis syndrome, with an increased risk of neoplasia and
      other health problems for both children and their relatives. The availability of
      molecular/genetic screening tests has increased early diagnosis of younger
      members of known polyposis families. This article reviews the gross and
      microscopic features of polyposis syndromes of childhood and summarizes the
      molecular/genetic advances in this field. Clinical management is also briefly
      discussed.

PMID- 14708732
TI  - Developmentally regulated expression of Survivin in human pancreatic islets.
AB  - Islet cell apoptosis plays a role in both normal development of the endocrine
      pancreas and in the pathogenesis of Type I and Type II diabetes. The molecular
      mechanisms regulating islet cell death and survival in both normal and
      pathological situations are still not completely elucidated. The inhibitor of
      apoptosis protein (IAP) Survivin has an anti-apoptotic function mediated by
      several mechanisms; these include inhibiting caspase 3 and caspase 7. Survivin
      expression has been reported in human fetal islets and it may play a role in
      pancreatic remodeling and islet homeostasis. However, there are no data
      concerning either its expression in neonate or adult islets or its expression in
      any specific subtype of islet cells. We identified Survivin expression by
      immunohistochemistry in alpha cells and beta islet cells of 5/5 fetal pancreases.
      In contrast, fetal delta cells failed to demonstrate any detectable level of
      Survivin expression. Survivin expression was subsequently lost in the beta cells
      but not the alpha cells of 5/5 newborns and 5/5 adult subjects. Neonatal and
      adult delta cells maintained the lack of Survivin expression seen in fetal
      islets. These data show that different subtypes of islet cells differ in their
      pattern of Survivin expression. Furthermore, expression of Survivin in the beta
      cells is developmentally regulated.

PMID- 14708733
TI  - Basal cells of second trimester fetal breasts: immunohistochemical study of
      myoepithelial precursors.
AB  - The molecular characterization of human mammary myoepithelial cells is
      incomplete, hindering our understanding of its importance in breast physiology
      and pathology. Because data on the precursors of this cell lineage remain scarce
      and often contradictory, basal epithelial cells of second trimester fetal breasts
      were studied by light microscopy (LM) and immunohistochemistry (IHC). Up to 20 wk
      of gestational age, the mammary rudiments only comprised roundish primary
      outgrowths, "primary buds," more likely to represent immature nipples than true
      mammary tissue. At 21 wk secondary outgrowths, "projections," extended from
      enlarged primary buds into well-vascularized layers of dense mesenchyme. Basal
      projection cells had a partial myoepithelial-like phenotype: they reacted with
      CD29, CD49f, CD104, keratin 14, vimentin, S100beta protein, and p63; furthermore,
      many became positive for keratin 17, alpha-smooth muscle actin, and CD10 (but not
      for keratin 19) between wk 21 and 25. The continuous basement membrane associated
      with the fetal mammary rudiments was strongly positive for collagens type IV and
      VII, and for laminin 5. Consistently strong and basally polarized staining for
      hemidesmosomal components suggested that although incompletely differentiated,
      most second trimester myoepithelial precursors might already mediate local
      epithelial-mesenchymal interactions, i.e., complex signaling pathways which are
      crucial for both orderly growth during development and maintenance of homeostasis
      during adult life. Because they are likely implicated in the phenomenon of
      menstrual cycle-related growth spurts in the adult resting breast, the
      strategically positioned cells of the myoepithelial lineage might constitute
      critical protagonists in defective epithelial-mesenchymal signaling associated
      with cancer progression.

PMID- 14708734
TI  - Parvovirus infects cardiac myocytes in hydrops fetalis.
AB  - Parvovirus infection during pregnancy is an important cause of hydrops fetalis.
      It is attributed to anemia caused by viral-induced destruction of red blood
      cells. Infection of other organs has been reported including the heart, liver,
      and lungs. Few of these reports, however, convincingly demonstrate virions within
      the functional parenchyma of the tissue. This is of particular concern regarding
      myocardium in the context of hydrops fetalis which is, in part, due to cardiac
      failure. The problem in routine pathology practice is that most fetuses with the
      infection are macerated. This, in part, probably explains the paucity of
      published information on cardiac involvement. This study examined five cases of
      fatal hydrops fetalis with variable maceration with serologically proven
      parvovirus B19 infection. Transmission electron microscopy of cardiac tissue
      demonstrated intranuclear virions in both erythroid precursor cells and in
      cardiac myocytes in three of these cases. In each of these, immuno-gold electron
      microscopy provided confirmatory evidence of parvovirus infection. Virions were
      not identifiable where maceration had caused disintegration of nuclei in the
      myocytes. In addition, virions were absent in the three negative control cases
      where retroplacental hemorrhage was confirmed as the cause of death. This study
      suggests that parvovirus infection of cardiac myocytes may play a more important
      role in causing hydrops fetalis than previously realized. It also demonstrates
      that maceration should not discourage the use of electron microscopy.

PMID- 14708735
TI  - Pathology of noncirrhotic portal hypertension: clinicopathologic study in
      pediatric patients.
AB  - From 1995-2002, 14 patients with predominantly prehepatic, noncirrhotic portal
      hypertension were evaluated. At presentation, the eight females and six males had
      a mean age of 9 years (range 2-18). Seven were admitted with gastrointestinal,
      mostly esophageal bleeding, three with splenomegaly, three with hepato-pulmonary
      syndrome, and one with hyperammonemia. Imaging studies showed portal vein
      obstruction in six patients and non-obstructed but frequently anomalous vascular
      patterns, including hypoplasia of the portal vein, in the remaining eight
      patients. At the onset, liver function was marginally abnormal in all patients,
      but thrombocytopenia of approximately 100 x 10(9)/L was consistently observed,
      probably reflecting chronic mild consumption coagulopathy and hypersplenism. The
      most striking and frequent histopathologic finding in 25 liver samples, was the
      presence of hypoplastic portal triads with collapsed portal vein radicles. In
      contrast, other triads showed markedly distended and misshapen portal vein
      radicles and likely lymphatics. These two patterns of collapse and distention
      presumably reflect areas of impaired versus overloaded intrahepatic portal venous
      flow. Some of the biopsies showed variable portal/sinusoidal fibrosis. Four
      patients (two with intestinal bleeding, two with hepatopulmonary syndrome)
      required liver transplants and are doing well. Eight patients are doing well
      clinically after surgical or spontaneous vascular shunting. Two patients with
      intestinal bleeding and hepato-pulmonary syndrome, respectively) who had
      congenital dyskeratosis, underwent bone marrow transplantation and died of
      nonhepatic-related complications. It is possible to suggest prehepatic causes of
      portal hypertension even in needle biopsies when collapsed portal vein radicles
      are present in portal triads, but more than one biopsy sample with larger bore
      bioptomes may be required to see the changes. Conversely, identifying these
      changes may suggest to the clinicians the need to work-up a patient for portal
      hypertension.

PMID- 14708736
TI  - Standards for dysmorphological diagnosis in human fetuses.
AB  - This study provides new standards for some fetal dimensions frequently concerned
      with dysmorphological syndromes. Seven dimensions were included: the outer and
      inner canthal distances (OCD and ICD), the anteroposterior and transversal ocular
      diameters, the biparietal diameter and head circumference, and the inter-nipple
      distance. Subjects came from a large data set including more than 4000 fetuses
      autopsied in fetopathology units of pediatric hospitals in Paris between 1986 and
      2001. From this data set, 673 subjects were carefully selected by exclusion of
      multiple pregnancies, macerated and malformed fetuses, and subjects with abnormal
      karyotypes and severe infections. Fetal ages ranged from 11 to 42 gestational wk,
      with a very large sample of fetuses in the first half of gestation. The standards
      of each dimension were computed in relation to age, as well as the ratio ICD/OCD.
      The mathematical models used to fit the percentile growth curves were carefully
      selected for each variable. This study supplies a set of accurate standards of
      specific dimensions useful for dysmorphological diagnosis in fetuses.

PMID- 14708737
TI  - Amniotic infection syndrome: nosology and reproducibility of placental reaction
      patterns.
AB  - Clinically responsive placental examination seeks to provide useful information
      regarding the etiology, prognosis, and recurrence risk of pregnancy disorders.
      The purpose of this study was to assemble and validate a complete set of the
      placental reaction patterns seen with amniotic fluid infection in the hope that
      this might provide a standardized diagnostic framework useful for practicing
      pathologists. Study cases (14 with amniotic fluid infection, 6 controls) were
      reviewed blindly by six pathologists after agreement on a standard set of
      diagnostic criteria. After analysis of initial results, criteria were refined and
      a second, overlapping set of cases were reviewed. Majority vote served as the
      gold standard. Grading and staging of maternal and fetal inflammatory responses
      was found to be more reproducible using a two- versus three-tiered grading system
      than a three- versus five-tiered staging system (overall agreement 81% vs. 71%).
      Sensitivity, specificity, and efficiency for individual observations ranged from
      67-100% (24/30 > 90%). Reproducibility was measured by unweighted kappa values
      and interpreted as follows: < 0.2, poor; 0.2-0.6, fair/moderate; > 0.6,
      substantial. Kappa values for the 12 lesions evaluated in 20 cases by the six
      pathologists were: acute chorioamnionitis/maternal inflammatory response (any,
      0.93; severe 0.76; advanced stage, 0.49); chronic (subacute) chorioamnionitis
      (0.25); acute chorioamnionitis/fetal inflammatory response (any, 0.90; severe,
      0.55; advanced stage, 0.52); chorionic vessel thrombi (0.37); peripheral
      funisitis (0.84); acute villitis (0.90); acute intervillositis/intervillous
      abscesses (0.65), and decidual plasma cells (0.30). Adoption of this clearly
      defined, clinically relevant, and pathologically reproducible terminology could
      enhance clinicopathologic correlation and provide a framework for future clinical
      research.

PMID- 14708738
TI  - Epstein-Barr virus-associated leiomyomatosis and posttransplant
      lymphoproliferative disorder in a child with severe combined immunodeficiency:
      case report and review of the literature.
AB  - The occurrence of smooth muscle neoplasms and lymphoproliferative disorders in
      immunocompromised patients is well recognized. We report the case of an 8-year
      old girl with adenosine deaminase (ADA)-deficient severe combined
      immunodeficiency (SCID) status post-bone marrow transplant (BMT), in whom Epstein
      Barr virus (EBV) was detected in innumerable leiomyomas involving the gallbladder
      (leiomyomatosis), and multifocal leiomyomas in liver, spleen, pancreas,
      intestinal tract, and lung. The leiomyomas of the gallbladder, liver, spleen, and
      lung were asymptomatic, while those located in the colon became clinically
      manifest by recurrent lower intestinal hemorrhage. The patient also developed
      extensive EBV-associated polymorphic lymphoproliferative disorder (PTLD) in nodal
      and extranodal sites. In addition, there were pulmonary and gastric adenovirus
      and small and large intestine cryptosporidum infections. Our case appears to be
      the first example of leiomyomatosis of the gallbladder coexisting with multifocal
      leiomyomas of the liver, spleen, pancreas, intestinal tract, and lung, as well as
      EBV-derived lymphoproliferative disorder in a young girl with ADA-deficient SCID.
      Awareness of the pattern of involvement and of the coexistence of benign
      leiomyomatous proliferations with lymphoproliferative disorder is of value when
      gallbladder, pancreatic, biliary tree, lung, and intestinal lesions become
      clinically manifest in these patients. The demonstration of EBV infection in both
      leiomyomata and the PTLD suggests a common pathogenesis that may have therapeutic
      and prognostic implications.

PMID- 14708739
TI  - Primary ocular adnexal lymphoma in pediatric patients: report of two cases and
      review of the literature.
AB  - Primary ocular adnexal lymphoma (POAL) is a rare extranodal lymphoma. The mucosa
      associated lymphoid tissue (MALT) subtype predominates and primarily occurs after
      the sixth decade of life. Most studies of ocular adnexal lymphoma are from the
      adult population. The data and experience in pediatric patients with POAL are
      limited to a few cases reported in the literature. Here we describe two pediatric
      cases of POAL and review the literature to further help characterize the clinical
      features and histopathologic appearance of this uncommon lymphoma.

PMID- 14708740
TI  - Adrenocortical and hepatic nodules within placental tissue.

PMID- 14708741
TI  - Microbial community responses to atrazine exposure and nutrient availability:
      linking degradation capacity to community structure.
AB  - Repeated pesticide exposure may enhance biodegradation through selective
      enrichment of pesticide-metabolizing microorganisms, particularly when the
      compound is used as a C and energy source. The relationship between pesticide
      application history and degradation rate is unclear when the chemical is utilized
      as a nutrient source other than C. Atrazine, a poor source of C and energy, was
      chosen as a model compound because it can serve as an N source for some
      microorganisms. Soils with (H-soil) and without (NH-soil) prior s-triazine
      treatment history were repeatedly exposed to atrazine and a variety of C and N
      source amendments. Exposure to atrazine and inorganic-N availability were the
      dominant factors leading to the development of microbial communities with an
      enhanced capacity to degrade atrazine. The density of the atrazine-degrading
      microorganisms increased immediately, up to 1000-fold, with atrazine exposure in
      the H-soil, but comparable increases were not observed in the NH-soil until 12
      weeks following laboratory acclimation, despite high rates of atrazine
      mineralization in these soils immediately following the acclimation period. Whole
      soil fatty acid methyl ester (FAME) analysis showed that the application of
      alternative C and N sources in addition to atrazine resulted in a microbial
      community composition that was distinctly different from that in either the
      atrazinealone treatment or water controls for both the H- and NH-soils. These
      data suggest that the microbial communities in both soils were altered
      differently in response to the treatments but developed a similar enhanced
      capacity to mineralize atrazine.

PMID- 14708742
TI  - Bacterial community dynamics during biostimulation and bioaugmentation
      experiments aiming at chlorobenzene degradation in groundwater.
AB  - A set of microcosm experiments was performed to assess different bioremediation
      strategies, i.e., biostimulation and bioaugmentation, for groundwater
      contaminated with chlorobenzenes. The biodegradative potential was stimulated
      either by the supply of electron acceptors (air, (NO3-), to increase the activity
      of the indigenous bacterial community, or by the addition of aerobic
      chlorobenzene-degrading bacteria (Pseudomonas putida GJ31, Pseudomonas aeruginosa
      RHO1, Pseudomonas putida F1deltaCC). Experiments were performed with natural
      groundwater of the aquifer of Bitterfeld, which had been contaminated with 1,2
      dichlorobenzene (1,2-DCB), 1,4-dichlorobenzene (1,4-DCB), and chlorobenzene (CB).
      The microcosms consisted of airtight glass bottles with 800 mL of natural
      groundwater and were incubated under in situ temperature (13 degrees C). Behavior
      of the introduced strains within the indigenous bacterial community was monitored
      by fluorescent in situ hybridization (FISH) with species-specific
      oligonucleotides. Dynamics of the indigenous community and the introduced strains
      within the microcosms were followed by single-strand conformation polymorphism
      (SSCP) analysis of 16S rDNA amplicons obtained from total DNA of the microbial
      community. An indigenous biodegradation potential under aerobic as well as
      anaerobic denitrifying conditions was observed accompanied by fast and specific
      changes in the natural bacterial community composition. Augmentation with P.
      aeruginosa RHO1 did not enhance bio-degradation. In contrast, both P. putida GJ31
      as well as P. putida F1deltaCC were capable of growing in groundwater, even in
      the presence of the natural microbial community, and thereby stimulating
      chlorobenzene depletion. P. putida GJ31 disappeared when the xenobiotics were
      depleted and P. putida F1deltaCC persisted even in the absence of CB. Detailed
      statistical analyses revealed that community dynamics of the groundwater
      microbiota were highly reproducible but specific to the introduced strain, its
      inoculum size, and the imposed physicochemical conditions. These findings could
      contribute to the design of better in situ bioremediation strategies for
      contaminated groundwater.

PMID- 14708743
TI  - The rate of change of a soil bacterial community after liming as a function of
      temperature.
AB  - The response of a bacterial community to liming of a forest humus soil (pH 4.9
      increased to pH 7.5) was studied in the laboratory at three temperatures (5, 20,
      and 30 degrees C). As a comparison an unlimed soil (pH 4.9) and a soil limed in
      the field 15 years ago (pH around 6) were also included. The bacterial community
      tolerance of pH was measured using TdR incorporation. The pH of the bacterial
      suspensions (bacteria directly extracted from soil) was altered to 3.6 and 8.3
      using different buffers before measuring TdR incorporation. The logarithmic ratio
      between TdR incorporation at 8.3 and 3.6 was then used as an indicator of the
      community pH tolerance. The rate of changes in the community tolerance to pH
      after liming was fastest for the soil incubated at 30 degrees C, but only minor
      differences in rate of change could be seen between samples incubated at 5 and 20
      degrees C. Changes in phospholipid fatty acid (PLFA) pattern after increasing the
      pH were most rapid for the bacterial community in the soil incubated at 30
      degrees C followed by the soil incubated at 20 degrees C, whereas no changes
      could be seen in the PLFA pattern of the soil incubated at 5 degrees C, even
      after 82 days' incubation. Thus, the changes in the PLFA pattern were
      considerably slower than the changes in bacterial community tolerance to pH
      measured using TdR incorporation.

PMID- 14708744
TI  - Structure of microbial communities in Sphagnum peatlands and effect of
      atmospheric carbon dioxide enrichment.
AB  - Little is known about the structure of microbial communities in Sphagnum
      peatlands, and the potential effects of the increasing atmospheric CO2
      concentration on these communities are not known. We analyzed the structure of
      microbial communities in five Sphagnum-dominated peatlands across Europe and
      their response to CO2 enrichment using miniFACE systems. After three growing
      seasons, Sphagnum samples were analyzed for heterotrophic bacteria,
      cyanobacteria, microalgae, heterotrophic flagellates, ciliates, testate amoebae,
      fungi, nematodes, and rotifers. Heterotrophic organisms dominated the microbial
      communities and together represented 78% to 97% of the total microbial biomass.
      Testate amoebae dominated the protozoan biomass. A canonical correspondence
      analysis revealed a significant correlation between the microbial community data
      and four environmental variables (Na+, DOC, water table depth, and DIN),
      reflecting continentality, hydrology, and nitrogen deposition gradients. Carbon
      dioxide enrichment modified the structure of microbial communities, but total
      microbial biomass was unaffected. The biomass of heterotrophic bacteria increased
      by 48%, and the biomass of testate amoebae decreased by 13%. These results
      contrast with the absence of overall effect on methane production or on the
      vegetation, but are in line with an increased below-ground vascular plant biomass
      at the same sites. We interpret the increase in bacterial biomass as a response
      to a CO2-induced enhancement of Sphagnum exudation. The causes for the decrease
      of testate amoebae are unclear but could indicate a top-down rather than a bottom
      up control on their density.

PMID- 14708745
TI  - Structure and seasonal dynamics of hyporheic zone microbial communities in free
      stone rivers of the western United States.
AB  - The hyporheic zone of a river is characterized by being nonphotic, exhibiting
      chemical/redox gradients, and having a heterotrophic food web based on the
      consumption of organic carbon entrained from surface waters. Hyporheic microbial
      communities constitute the base of food webs in these environments and are
      important for maintaining a functioning lotic ecosystem. While microbial
      communities of rivers dominated by fine-grained sediments are relatively well
      studied, little is known about the structure and seasonal dynamics of microbial
      communities inhabiting the predominantly gravel and cobble hyporheic zones of
      rivers of the western United States. Here, we present the first molecular
      analysis of hyporheic microbial communities of three different stream types
      (based on mean base discharge, substratum type, and drainage area), in Montana.
      Utilizing 16S rDNA phylogeny, DGGE pattern analysis, and qPCR, we have analyzed
      the prokaryotic communities living on the 1.7 to 2.36 mm grain-size fraction of
      hyporheic sediments from three separate riffles in each stream. DGGE analysis
      showed clear seasonal community patterns, indicated similar community composition
      between different riffles within a stream (95.6-96.6% similarity), and allowed
      differentiation between communities in different streams. Each river supported a
      unique complement of species; however, several phylogenetic groups were conserved
      between all three streams including Pseudomonads and members of the genera
      Aquabacterium, Rhodoferax, Hyphomicrobium, and Pirellula. Each group showed
      pronounced seasonal trends in abundance, with peaks during the Fall. The
      Hyphomicrobium group was numerically dominant throughout the year in all three
      streams. This work provides a framework for investigating the effects of various
      environmental factors and anthropogenic effects on microbial communities
      inhabiting the hyporheic zone.

PMID- 14708746
TI  - Comparison of subsurface and surface soil bacterial communities in California
      grassland as assessed by terminal restriction fragment length polymorphisms of
      PCR-amplified 16S rRNA genes.
AB  - The integrated biomass beneath the surface horizon in unsaturated soils is large
      and potentially important in nutrient and carbon cycling. Compared to surface
      soils, the ecology of these subsurface soils is weakly understood, particularly
      in terms of the composition of bacterial communities. We compared soil bacterial
      communities along two vertical transects by terminal restriction fragment length
      polymorphisms (TRFLPs) of PCR-amplified 16S rRNA genes to determine how surface
      and deep bacterial communities differ. DNA yield from soils collected from two
      Mediterranean grassland transects decreased exponentially from the surface to 4 m
      deep. Richness, as assessed by the number of peaks obtained after restriction
      with HhaI, MspI, RsaI, or HaeIII, and diversity, as assessed by the Shannon
      diversity indices, were lowest in the deepest sample. Lower diversity at depth is
      consistent with species-energy theory, which would predict relatively low
      diversity in the low organic matter horizons. Principal components analysis
      suggested that, in terms of HhaI and HaeIII generated TRFLPs, bacterial
      communities differed between depths. The most abundant amplicons cloned from the
      deepest sample contained sequences with restriction sites consistent with the
      largest peaks observed in TRFLPs generated from deep samples. These more abundant
      operational taxonomic units (OTUs) appeared related to Pseudomonas and
      Variovorax. Several OTUs were more related to each other than any previously
      described ribotypes. These OTUs showed similarity to bacteria from the divisions
      Actinobacteria and Firmicutes.

PMID- 14708747
TI  - Comparison of free-living and particle-associated bacterial communities in a
      coastal lagoon.
AB  - We analyzed, by terminal restriction fragment length polymorphisms (T-RFLPs) of
      PCR-amplified 16S rDNA, microbial diversity in water collected during the dry and
      wet seasons in a human-impacted coastal lagoon. Water samples were fractionated
      by prefiltration to differentiate particle-associated and free-living microbes.
      From a sample collected during the dry season, prefiltration removed 23 to 44% of
      bacteria, as assessed by direct counts and MPN, and 99% of phytoplankton, as
      assessed by chlorophyll a. Restriction with RsaI yielded fewer peaks than
      restriction with HhaI. Diversity indices calculated from T-RFLPs were higher in
      the lagoon than adjoining coastal waters and higher in the particle-associated
      than the free-living fraction. In the dry season, peaks found only in bulk and
      particle-associated T-RFLPs were consistent with plastid and cyanobacterial
      ribotypes. These peaks matched those observed in the sequence of a clone
      generated from the bulk fraction with plastid and cyanobacterial specific
      primers. This clone appeared related to plastids found in the diatom genus
      Skeletonema. Principal component analysis of T-RFLPs suggested that the
      difference between the free-living and particle-associated fractions in the dry
      season was less than temporal variability in this lagoon and that these fractions
      varied significantly only in the wet season. This fractionation of microbial
      populations into particle-associated and free-living guilds during the wet
      season, when water residence time in the lagoon is relatively low, suggests an
      external source of particle-associated bacteria such as erosion of upland soils
      by runoff.

PMID- 14708748
TI  - Archaeal nucleic acids in picoplankton from great lakes on three continents.
AB  - Phylogenetic analysis of PCR-amplified 16S rRNA genes revealed the presence of
      archaea in picoplankton collected from the Laurentian Great Lakes in North
      America, Africa's Lake Victoria, and Lakes Ladoga and Onega in northeastern
      Eurasia. From 1 to 10% of the rRNA extracted from size-fractionated picoplankton
      (>0.2 microm but <1.2 microm) collected in the epilimnion and hypolimnion of
      these lakes was specific to the Archaea, whereas the majority of rRNA was derived
      from Bacteria. Analysis of the 16S rRNA genes cloned from these samples indicated
      they were closely related to crenarchaeal sequences that have been widely
      characterized from marine environments. The presence of nearly identical 16S rDNA
      clones in several of these geographically disparate lakes suggests a cosmopolitan
      distribution of specific subgroups of these Archaea in freshwater environments.
      Despite their abundance in the water column of freshwater lakes, we have no
      representatives of these crenarchaea in pure culture, and so their physiological
      characteristics and ecological role remain unknown.

PMID- 14708749
TI  - Viral abundance and a high proportion of lysogens suggest that viruses are
      important members of the microbial community in the Gulf of Trieste.
AB  - Epifluorescence microscopy and transmission electron microscopy were applied to
      study virioplankton community in the Gulf of Trieste (northern Adriatic Sea). The
      total viral abundance was in a range between 2.5 x 10(9)/L and 2.9 x 10(10)/L and
      was positively correlated with trophic status of the environment. Viruslike
      particles were significantly correlated with bacterial abundance in all samples
      studied. Correlations with other physicochemical or biological parameters were
      not significant. The data suggest that, because of the substantial fraction of
      tailed viruses present (26%), bacteriophages are an important component of the
      virioplankton community in the Gulf of Trieste. The abundance of viruslike
      particles in the seawater changed at hour intervals in a range from 1.3 x 10(9)/L
      to 5.1 x 10(9)/L. A significant fraction (71%) of the bacterial isolates was
      inducible in vitro by mitomycin C, and a high occurrence (51%) of lysogenic
      isolates with more than one phage morphotype present in the lysate was detected.
      The presence of lysogenic bacteria in the seawater was confirmed in situ with a
      mitomycin C induction experiment on the natural bacterial population. Results
      suggest that virioplankton is an abundant component of the microbial community in
      the Gulf of Trieste.

PMID- 14708750
TI  - Diversity of Geobacteraceae species inhabiting metal-polluted freshwater lake
      sediments ascertained by 16S rDNA analyses.
AB  - The abundance, distribution, and phylogenetic diversity of members of the Fe(III)
      reducing family Geobacteraceae were studied along a gradient of metal
      contaminants in Lake Coeur d'Alene, Idaho. Partial 16S rRNA gene fragments were
      amplified by PCR using primers directed toward conserved regions of the gene
      within the family Geobacteraceae. Analysis of amplicons separated by denaturing
      gradient gel electrophoresis (DGGE) suggested within-site variation was as great
      as between-site variation. Amplicons were cloned and grouped by RFLP type and
      DGGE migration distance and representatives were sequenced. Grouping clones with
      3% or less sequence dissimilarity, 15 distinct phylotypes were identified
      compared to 16 distinct DGGE bands. Only 1 phylotype was recovered from all
      sites. This clone, B14, is most closely related to Geobacter metallireducens and
      constituted a greater portion of the pristine community than of the contaminated
      communities. A second phylotype, Q2, predominated in the contaminated communities
      and was notably absent from the pristine libraries. Clone Q2 presents a high
      degree of sequence similarity to two Geobacter spp. previously isolated from this
      region of Lake Coeur d'Alene. Six phylotypes were unique to the contaminated
      sediments, whereas two were found only in the pristine sediments. Indices of
      diversity (Shannon and Simpson) were consistently higher when calculated with
      DGGE data than when clone library data were used. Most-probable-number PCR and
      real-time PCR suggested that the Geobacteraceae phylotypes were spread relatively
      evenly across all three sites along the gradient. Our data indicate that the
      Geobacteraceae are diverse and abundant in Lake Coeur d'Alene sediments,
      regardless of metals content. These results provide insight into the ability of
      dissimilatory Fe(III)-reducing bacteria to colonize habitats with elevated metal
      concentrations, and they have important implications for the management and
      remediation of metal-contaminated sites.

PMID- 14708751
TI  - Analysis of methanogen diversity in a hypereutrophic lake using PCR-RFLP analysis
      of mcr sequences.
AB  - The incidence and diversity of methanogens in Priest Pot, a dynamic and active
      lake, were monitored by analysing mcrA gene sequences generated from total DNA
      samples obtained at different times of the year and amplified using the
      polymerase chain reaction. A number of mcrA clones were analysed by developing an
      RFLP-based protocol to generate a number of restriction patterns that were
      assigned to a number of classes. The RFLP patterns for each class were compared
      with published sequence information for mcrA from cultured methanogens as well as
      with those from other experimental studies. They could be used to assign
      tentative identification for some of the Priest Pot clones and also revealed the
      presence of a number of clones that could not be affiliated to any known
      methanogens. The limitations of using RFLP profiles of mcrA gene sequences for
      studying methanogen ecology are discussed.

PMID- 14708752
TI  - Dynamics of microcystin-degrading bacteria in mucilage of Microcystis.
AB  - To reveal the process of degradation of hepatotoxic microcystin produced in
      Microcystis cells during the Microcystis bloom period, we used fluorescence in
      situ hybridization (FISH) to analyze the population dynamics of microcystin
      degrading bacteria in Microcystis mucilage. We designed and applied an
      oligonucleotide probe targeted to the 16S rRNA sequence of strain Y2 of a
      microcystin-degrading bacterium (MCD-bacterium), which was isolated from Lake
      Suwa, Japan. In both the 1998 and 1999 tests, FISH clearly showed that MCD
      bacteria existed in the mucilage and that, when a high concentration of cell
      bound microcystin was detected, MCD-bacteria exceeded 10% of the sum of bacteria
      hybridized with group-specific probes. The concentration of MCD-bacteria was
      highest in summer 1998, when a toxic species, M. viridis, was dominant. There was
      a high correlation between the number of MCD-bacteria in the mucilage and the
      concentration of cell-bound microcystin in the lake. Our results suggest that MCD
      bacteria responded to changes in the concentration of microcystin and degraded
      the microcystin when it was released from Microcystis cells. We also analyzed
      changes in the bacterial community structure associated with the Microcystis
      colonies by using domain- and group-specific oligonucleotide probes. Changes in
      the concentrations of the Cytophaga/Flavobacterium group and delta
      Proteobacteria, which can degrade macromolecules derived from Microcystis cells,
      were synchronized with changes in the concentration of Microcystis. The results
      not only suggest the significant role of MCD-bacteria in detoxification, but also
      demonstrate a possible sequence of degradation from Microcystis cells to
      microcystin maintained in the cell, which is then carried out by bacterial
      consortia in the mucilage.

PMID- 14708753
TI  - Ultrasound registration of the bone surface for surgical navigation.
AB  - OBJECTIVE: To allow non-invasive registration of the bone surface for computer
      assisted surgery (CAS), this investigation reports the development and evaluation
      of intraoperative registration using 2D ultrasound (US) images. This approach
      employs automatic segmentation of the bone surface reflection from US images
      tagged with the 3D position to enable the application of CAS to minimally
      invasive procedures. METHODS: The US-based registration method was evaluated in
      comparison to point-based registration, which is the predominant method in
      current clinical use. The absolute accuracy of the US-based registration was
      determined using a phantom pelvis, with fiducial registration providing the
      ground truth. The relative accuracy was determined by an intraoperative study
      comparing the US registration to the point-based registration obtained as part of
      the HipNav experimental protocol. RESULTS: The phantom pelvis study demonstrated
      equivalent accuracy between point- and US-based registration under in vitro
      conditions. In the intraoperative study, the US-based registration was
      sufficiently consistent with the point-based registration to warrant larger-scale
      clinical trials of this non-invasive registration method. CONCLUSION: Ultrasound
      based registration eliminates the need for physical contact with the bone surface
      as in point-based registration. As a result, non-invasive registration could
      fully unlock the potential of computer-assisted surgery, enabling development of
      the next generation of minimally invasive surgical procedures.

PMID- 14708754
TI  - Automated fiducial marker detection for patient registration in image-guided
      neurosurgery.
AB  - OBJECTIVE: The registration of applied fiducial markers within the preoperative
      data is often left to the surgeon, who has to identify and tag the center of each
      marker. This is both time-consuming and a potential source of error. For this
      reason, the development of an automated procedure was desirable. In this study,
      we have investigated the accuracy of a software algorithm for detecting fiducial
      markers within the navigation data set. The influence of adjustable values for
      accuracy and threshold on the sensitivity and specificity of the detection
      process, as well as the time gain, was investigated. PATIENTS AND METHODS: One
      hundred MP-RAGE MRI data sets of patients with different pathologies who were
      scheduled for image-guided surgery were used in this study. A total of 591
      applied fiducial markers were to be detected using the algorithm of the software
      VVPlanning 1.3 (BrainLAB, Heimstetten, Germany) on a Pentium II standard PC. The
      size value of a marker in the y-direction is called "accuracy" and depends on the
      slice thickness. "Threshold" describes the gray level above which the algorithm
      starts searching for pixel clusters. The threshold value was changed stepwise on
      the basis of a constant "accuracy" value. The "accuracy" value was changed on the
      basis of that threshold value at which all markers were detected correctly.
      RESULTS: The time needed for automatic detection varied between 12 s and 25 s. An
      optimum value for adjustable marker size was found to be 1.1 mm, with 8
      undetected markers (1.35%) and 7 additionally detected structures (1.18%) out of
      591. The mean gray level (Threshold) for all data sets above which marker
      detection was correct was 248.9. The automatic detection of markers was good for
      higher gray levels, with 11 missed markers (1.86%). Starting the algorithm at
      lower gray levels led to a decreased incidence of missed markers (0.17%), but
      increased the incidence of additionally detected structures to 27.92%.
      CONCLUSION: The automatic marker-detection algorithm is a robust, fast and
      objective instrument for reliable fiducial marker registration when used with
      optimum settings for both threshold and accuracy.

PMID- 14708755
TI  - Analysis of procedure time in robot-assisted surgery: comparative study in
      laparoscopic cholecystectomy.
AB  - INTRODUCTION: Robotic surgery systems have been introduced to deal with the basic
      disadvantages of laparoscopic surgery. However, working with these systems may
      lead to time loss due to additional robot-specific tasks, such as set-up of
      equipment and sterile draping of the system. To evaluate loss of time in robot
      assisted surgery, we compared 10 robot-assisted cholecystectomies to 10 standard
      laparoscopic cholecystectomies. MATERIALS AND METHODS: The robot-assisted
      procedures were performed with the da Vinci telemanipulation system. The total
      time in the operating room (OR) was scored and divided into preoperative,
      operative, and postoperative phases. These phases were further divided into
      smaller time-frames to precisely define moments of time loss. RESULTS: The most
      significant difference between the two groups was found in the preoperative
      phase. Robot-related tasks led to time loss in all time-frames of this phase. In
      the operative phase, the trocar entry time-frame was longer in robot-assisted
      cases than in standard procedures. Additionally, postoperative OR clearing was
      longer in the robot-assisted cases. Total operating time did not differ
      significantly between the two procedures. CONCLUSION: Robot-assisted surgery
      leads to time loss during preparation of routine laparoscopic procedures.

PMID- 14708756
TI  - Accurate determination of a joint rotation center based on the minimal amplitude
      point method.
AB  - In many computer-assisted surgery procedures in the field of joint replacement a
      joint rotation center must be located. To this end, joints such as the hip or the
      shoulder are approximated as spherical joints, and the most commonly used
      numerical method is the sphere-fitting algorithm. However, this method has a
      numerical instability where there is a limited range of motion caused by, for
      example, joint impingement. The aim of the present study was to develop an
      alternative kinematic method called the minimal amplitude point method. This
      method estimates the localization of the rotation center and can easily be
      integrated into program codes of computer-assisted surgery modules. It mainly
      consists of identifying the point of a mobile segment that moves least in the
      reference coordinate system of an immobile segment using an optimization
      procedure (genetic algorithm). The point determined can then be assumed to be the
      rotation center of the joint. To compare results of the two methods, an
      experimental set-up of two rigid solids linked by a spherical joint with known
      geometry was used to compute the rotation center. In contrast to the sphere
      fitting method, the minimal amplitude point method permits the evaluation of the
      rotation center with an error of less than 4.1 mm, having a range of motion (ROM)
      of 5 degrees. An equivalent accuracy for the sphere-fitting method requires an
      ROM of 45 degrees.

PMID- 14708757
TI  - C-arm-based three-dimensional navigation: a preliminary feasibility study.
AB  - OBJECTIVE: With the new Siremobil Iso-C3D C-arm, three-dimensional (3D) datasets
      can be acquired intraoperatively in near-real time. Preliminary studies
      investigated the advantages of this system for depiction in joint and spinal
      surgery. Three-dimensional navigation seems feasible using the DICOM dataset of
      the Siremobil Iso-C3D in navigation devices. An experimental study was designed
      to investigate the feasibility and accuracy of this new technique. MATERIALS AND
      METHODS: After implantation of fiducial markers (titanium mini-screws,
      Leibinger), a Siremobil Iso-C3D C-arm with standard imaging options was used to
      acquire pre-interventional 3D datasets of the specimens. These isotropic voxel
      data were transferred via DICOM to a medivision navigation system using the spine
      module. After registration of the fiducials, a total of 20 pedicle screws were
      implanted (in 4 artificial-bone vertebral bodies and 6 cadaver vertebrae in situ)
      with the use of the navigation system in real-time mode. Post-interventionally,
      Iso-C3D and CT scans were obtained to control for implant position in the cadaver
      study. RESULTS: Fiducial marker implantation and registration require a special
      protocol to ensure correct identification and patient orientation in the DICOM
      dataset. The obtained accuracy was within 2 mm. Post-interventional imaging of
      the cadaveric vertebrae showed 10 of 12 screws to be correctly placed, with the
      other two in marginal intraosseous positions. CONCLUSIONS: Three-dimensional
      navigation with the Siremobil Iso-C3D data set is feasible, the accuracy being
      comparable to that of CT-based navigation and adequate for clinical
      interventions. Fiducial marker-based registration allows navigation of different
      bones in the same dataset without additional 3D scanning. This method is very
      useful as an additional tool in registration-free Iso-C3D-based navigation, since
      the navigation system allows the use of only one dynamic reference base (DRB).

PMID- 14708758
TI  - Experimental robotic milling in skull-base surgery.
AB  - OBJECTIVE: In the field of otorhinolaryngology, a variety of skull implants have
      been developed to assist hearing-impaired or even deaf patients. The first step
      in the implantation procedure, and also in lateral skull-base surgery, is to
      drill the calvarian or mastoid bone. We intended to investigate the hitherto
      unknown parameters for performing this procedure and to establish the first set
      up for robotic milling of the lateral skull base. MATERIALS AND METHODS:
      Experimental milling of the skull base was conducted on two human specimens using
      a hexapod robot. RESULTS: Optimized parameters were determined with a drill speed
      of 30,000 revolutions/min and a form feed rate of 5 mm/s for the calvarium and 1
      mm/s for mastoid bone, respectively, in a spiral-path fashion. While using a
      cutting burr, mean force levels were 4.81 N for calvarian bone and 6.12 N for
      mastoid bone, respectively--well below our empirical limit of 10 N. However,
      maximum levels easily surpassed these limits, reaching 27.7 N. CONCLUSION: The
      prerequisites for robotic skull-base surgery were fulfilled. With further work to
      implement feedback of sensory input, robots may increase precision for various
      tasks in skull-base surgery.

PMID- 14708765
TI  - Influence of solution and gas phase processes on protein-carbohydrate binding
      affinities determined by nanoelectrospray Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - The influence of solution pH, analyte concentration and in-source dissociation on
      the measurement of the association constant for a single chain variable fragment
      of a monoclonal antibody (scFv) and its native trisaccharide ligand by
      nanoelectrospray-Fourier transform ion cyclotron resonance mass spectrometery has
      been systematically investigated. From the results of this study, experimental
      conditions that preserve the original distribution of bound and unbound protein
      in solution into the gas phase, such that the nanoES mass spectrum provides a
      quantitative measure of the solution composition, were identified. These include
      the use of short spray durations (<10 min) to minimize pH changes, equimolar
      concentrations of protein and ligand to minimize the formation of nonspecific
      complexes, and short accumulation times (<2 s) in the hexapole of the ion source
      to avoid collisional heating and dissociation of the gaseous complex. Application
      of this methodology to the scFv and a series of carbohydrate ligands yields
      results that are in agreement with values previously determined by isothermal
      titration calorimetry. Competitive binding experiments performed on solutions
      containing the scFv and a mixture of carbohydrate ligands were also found to
      yield accurate association constants.

PMID- 14708772
TI  - Immobilized enzyme electron spin resonance: a method for detecting enzymatically
      generated transient radicals.
AB  - The study of enzymatically generated, transient radicals provides valuable
      information about radical reactivity as well as enzyme function. ESR methods to
      detect transient radicals are generally based on continuous flow and have the
      potential to consume large quantities of enzyme, substrate, and buffer.
      Experimental approaches have been pursued to minimize sample volumes, although
      none have made the continuous-flow ESR approach generally applicable for enzymes
      and substrates available in limited quantities. We have developed an alternative
      approach to the traditional continuous-flow ESR method that provides the same
      high-resolution ESR spectra, but does not consume large quantities of enzyme,
      substrate, or buffer. The method utilizes enzyme immobilized onto an inert
      substrate packed directly into an ESR flat cell. Flowing substrate solution over
      the immobilized enzyme generates in situ, transient radicals, which can then be
      observed on the submillisecond time scale. We have termed this method
      "immobilized enzyme ESR," abbreviated IE-ESR. In this paper, we have described
      the details of the IE-ESR technique and have presented data collected using the
      IE-ESR technique for transient radicals from limited quantity enzymes, limited
      quantity substrates, and D2O buffers. An extension of this technique to ESR spin
      trapping has also been discussed.

PMID- 14708773
TI  - Resolution of multiple ssDNA structures in free solution electrophoresis.
AB  - By using high concentrations of buffer, electroosmotic flow within uncoated
      channels of a microfluidic chip was minimized, allowing the free solution
      electrophoretic separation of DNA. More importantly, because of the ability to
      efficiently dissipate heat within these channels, field strengths as high as 600
      V/cm could be applied with minimal Joule heating (<2 degrees C). As a result of
      the higher field strengths, separations within an 8-cm-long channel were achieved
      within a few minutes. However, when the electrophoretic separation of single
      stranded DNA (ssDNA) less than 22 bases in length was performed, containing the
      fluorophore Texas Red as an end label, more than the expected single peak was
      observed at this high electric field. On the other hand, the free solution
      electrophoresis of a double-stranded DNA (dsDNA) consisting of a random sequence
      did exhibit the expected single peak. The appearance of these multiple peaks for
      ssDNA is shown to be dependent upon the base content and sequence of the ssDNA as
      well as on the chemical structure of the fluorophore used to tag the DNA for
      detection. Specifically, the peaks can be attributed to different secondary
      structures that result either from hydrophobic interactions between the DNA bases
      and an uncharged fluorescent dye or from G-quadruplexes within guanine-rich
      strands.

PMID- 14708776
TI  - Direct dating of archaeological pottery by compound-specific 14C analysis of
      preserved lipids.
AB  - A methodology is described demonstrating the utility of the compound-specific 14C
      technique as a direct means of dating archaeological pottery. The method uses
      automated preparative capillary gas chromatography employing wide-bore capillary
      columns to isolate individual compounds from lipid extracts of archaeological
      potsherds in high purity (>95%) and amounts (>200 microg) sufficient for
      radiocarbon dating using accelerator mass spectrometry (AMS). A protocol was
      developed and tested on n-alkanes and n-carboxylic acids possessing a broad range
      of 14C ages. Analytical blanks and controls allowed background 14C measurements
      to be assessed and potential sources of errors to be detected, i.e.,
      contamination with modern or dead 14C, isotopic fraction effects, etc. A "Russian
      doll" method was developed to transfer isolated target compounds onto tin
      powder/capsules prior to combustion and AMS analyses. The major advantage of the
      compound-specific technique is that 14C dates obtained for individual compounds
      can be directly linked to the commodities processed in the vessels during their
      use, e.g., animal fats. The compound-specific 14C dating protocol was validated
      on a suite of ancient pottery whose predicted ages spanned a 5000-year date
      range. Initial results indicate that meaningful correlations can be obtained
      between the predicted date of pottery and that of the preserved lipids. These
      findings constitute an important step forward to the direct dating of
      archaeological pottery.

PMID- 14708777
TI  - Quantitation of underivatized free amino acids in mammalian cell culture media
      using matrix assisted laser desorption ionization time-of-flight mass
      spectrometry.
AB  - In this investigation, a quantitative matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry (MALDI-TOFMS) method was developed for the
      analysis of underivatized free amino acids in mammalian cell culture media.
      Calibration curves were developed for 12 amino acids over the linear range of 1
      100 microM with coefficients of determination ranging from r2 = 0.9220 to r2 =
      0.9973. An aerospray method was utilized for the sample deposition method, and
      the matrix, alpha-cyano-4-hydroxycinnamic acid, served as the internal standard.
      This assay was used to analyze bioreactor samples from five time points in the
      process. Concentrations determined through interpolation of the calibration
      curves were comparable to those obtained via reversed-phase HPLC based analysis
      with an average percent difference of 19.71%. Repeatability and intermediate
      precision studies were also performed, and the relative standard deviations
      ranged from 0.5943 to 21.41 and 3.157 to 18.97, respectively.

PMID- 14708778
TI  - Reproducibility of quantitative proteomic analyses of complex biological mixtures
      by multidimensional protein identification technology.
AB  - If quantitative proteomic technologies are to be of widespread use to the
      biological community, the reproducibility of each method must be investigated and
      determined. We have analyzed the reproducibility of complex quantitative
      proteomic analyses of metabolically labeled S. cerevisiae analyzed via
      multidimensional protein identification technology (MudPIT). Three independent
      cell growths of S. cerevisiae grown in rich and minimal media and independent
      MudPIT analyses of each were compared and contrasted. Quantitative MudPIT was
      found to be intra- and interexperimentally reproducible at both the peptide and
      protein levels. Proteins of potential low abundance were detected, identified,
      and quantified by identical peptides from three independent samples. In addition,
      when multiple peptides were matched to a protein, the relative abundance of each
      peptide was in agreement across the three samples. Despite the reproducibility,
      errors in the experimental determination of protein expression levels occurred,
      but the impact of the variation was minimized by replicate experiments. Last,
      quantitative MudPIT analyses will likely be improved by increasing the number of
      peptide hits per protein in a given analysis, which will provide for greater
      intraexperimental reproducibility.

PMID- 14708781
TI  - Characterization of DNA immobilization and subsequent hybridization on a 2D
      arrangement of streptavidin on a biotin-modified lipid bilayer supported on SiO2.
AB  - We show how the water content (and effective density) of thin adsorbed films
      composed of biomolecules can be determined using combined quartz crystal
      microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance
      (SPR) analysis. In particular, these techniques, combined with theoretical
      treatment using a Voigt-based viscoelastic model, were applied to analyze the
      state of surface immobilized single stranded biotin-modified probe DNA (b-DNA)
      coupled via streptavidin to a biotin-doped supported phospholipid bilayer (b
      SPB)). From a proper analysis, it is demonstrated how changes in effective
      thickness, delta(f), and the viscoelastic components (shear viscosity, eta(f),
      and shear elasticity, mu(f))) can be obtained during both DNA immobilization and
      hybridization with single stranded fully complementary target DNA. In particular,
      it is demonstrated how this type of analysis can be used to control the state of
      streptavidin arrangement for improved measurements of DNA hybridization kinetics.
      The latter is demonstrated by identifying a surface-coverage dependent
      viscoelastic behavior of immobilized b-DNA, which is shown to influence the
      hybridization efficiency.

PMID- 14708785
TI  - High-throughput nuclear magnetic resonance analysis using a multiple coil flow
      probe.
AB  - An automated method for high-throughput nuclear magnetic resonance (NMR)
      spectroscopy has been developed using a four-coil Multiplex NMR probe. The probe
      is constructed with solenoidal microcoils optimized for detection of small
      volume, mass-limited samples and a flow-through design. Four samples can be
      simultaneously injected into the Multiplex probe with a robotics liquid handler
      and then analyzed in rapid succession using a selective excitation experiment.
      Due to the simultaneous injection of four samples and the reduced analysis time
      with rapid selective excitation, the analysis rate achieved thus far is as low as
      1 sample/34 s for 1D 1H NMR.

PMID- 14708787
TI  - Simultaneous quantitative analysis of anionic, cationic, and nonionic surfactants
      in water by electrospray ionization mass spectrometry with flow injection
      analysis.
AB  - A rapid method is described for the quantitative analysis of anionic, cationic,
      and nonionic surfactants in water samples by flow injection analysis coupled to
      electrospray ionization mass spectrometry (FIA/ESI-MS). All surfactants were
      isolated by liquid-liquid extraction and quantified using labeled triethoxylated
      nonylphenol ([13C6]-NP3EO) and sodium dibutylnaphthalenesulfonate as internal
      standards. FIA/ESI-MS was performed by alternating both positive and negative
      ionization modes, which allows simultaneous analysis of most common surfactants
      in a short time. Quality parameters of the method, such as linear range,
      repeatability, reproducibility, and limits of detection were studied. This method
      was applied to the analysis of wastewater treatment plant effluents from
      Catalonia (NE Spain).

PMID- 14708788
TI  - Development of high-sensitivity ion trap ion mobility spectrometry time-of-flight
      techniques: a high-throughput nano-LC-IMS-TOF separation of peptides arising from
      a Drosophila protein extract.
AB  - A linear octopole trap interface for an ion mobility time-of-flight mass
      spectrometer has been developed for focusing and accumulating continuous beams of
      ions produced by electrospray ionization. The interface improves experimental
      efficiencies by factors of approximately 50-200 compared with an analogous
      configuration that utilizes a three-dimensional Paul geometry trap (Hoaglund
      Hyzer, C. S.; Lee, Y. J.; Counterman, A. E.; Clemmer, D. E. Anal. Chem. 2002, 74,
      992-1006). With these improvements, it is possible to record nested drift
      (flight) time distributions for complex mixtures in fractions of a second. We
      demonstrate the approach for several well-defined peptide mixtures and an
      assessment of the detection limits is given. Additionally, we demonstrate the
      utility of the approach in the field of proteomics by an on-line, three
      dimensional nano-LC-ion mobility-TOF separation of tryptic peptides from the
      Drosophila proteome.

PMID- 14708790
TI  - Calibration of ion effective temperatures achieved by resonant activation in a
      quadrupole ion trap.
AB  - The present paper describes a calibration of the ion effective temperatures as a
      function of the resonant activation amplitude in a quadrupole ion trap mass
      spectrometer. MS/MS experiments are performed on leucine enkephalin (M + H)+,
      bradykinin (M + H)+, (M + 2H)2+, and (M + 3H)3+, and ubiquitin (M + 11H)11+. For
      each amplitude, the effective temperature is calculated as the temperature that
      would give the same dissociation rate constant as the one observed and is
      calculated using published Arrhenius parameters. The effective temperature is
      found to be linearly dependent on the activation amplitude on the range
      investigated. The dependence of the slope and of the intercept of the T(eff) = f
      (amplitude) functions on the parent ion m/z is examined and an equation is
      derived to calibrate the ion effective temperature between 365 and 600 K. Below
      365 K, a deviation from linearity is expected. Above 600 K, the validity of the
      equation will depend on whether the rapid energy exchange limit is still reached.
      Calculating backward, the Arrhenius parameters from the measured dissociation
      rates using this calibration show excellent agreement with the published values.
      The calibration can therefore be used to determine Arrhenius activation
      parameters from dissociation kinetics under resonant activation in quadrupole ion
      trap mass spectrometers.

PMID- 14708789
TI  - Laser desorption and imaging of proteins from ice via UV femtosecond laser
      pulses.
AB  - We have employed 200-fs, 400-nm laser pulses to desorb intact protein molecular
      ions directly from a frozen aqueous matrix. The resulting spectra obtained using
      a variety of proteins varying in molecular weight from 1060 (bradykinin) to 5778
      Da (insulin) are compatible with those obtained with traditional matrix-assisted
      laser desorption/ionization experiments. High-quality spectra could be generated
      using a fluence of 4.0-9.0 J/cm2 to desorb proteins from an aqueous solution
      frozen onto metal substrates with a sensitivity in the femtomole range. Although
      the mechanism behind this effect is still not clear, we speculate that it
      involves explosive boiling of the ice layer due to rapid heating of the
      substrate. Imaging experiments conducted on the ice layer suggest that the yield
      of protein is approximately independent of the film thickness and is very
      reproducible from shot to shot. The results are particularly significant since
      they open the possibility of examining a range of biomaterials directly from the
      in vivo aqueous environment.

PMID- 14708791
TI  - Study of lipid and apolipoprotein binding interactions using vesicle affinity
      capillary electrophoresis.
AB  - Vesicle affinity capillary electrophoresis (VCE), a newly developed technique,
      was designed to assess the effect of physicochemical properties of apolipoprotein
      (apo) on the binding to lipoproteins, under physiological conditions (phosphate
      saline buffer system at pH 7.4 and 37 degrees C), using vesicle as a model. The
      technique results in similar lipid binding properties of apo CIII (CIII) and its
      peptides compared to other techniques. It also offers a fast and more sensitive
      tool in determining the lipid affinity of apos in a unique system simulating the
      dynamic binding properties of apo in vivo. A noncompetitive binding model is used
      to determine the multiple binding properties of CIII and its peptides to vesicle.
      The VCE binding constants are dependent on temperature, physicochemical
      properties of the protein (hydrophobicity and charge), and nature of the vesicle.
      The vesicles used in the VCE experiments described here have been fully
      characterized and found to be stable under different temperatures (4 and 37
      degrees C) and voltage conditions. Migration behavior of CIII and related
      peptides is reported in terms of relative mobility in order to correct for
      variability in viscosity at different vesicle concentrations. The VCE method
      provides very precise data on the migration time from 0.1 to 3.3% RSD at the
      highest concentration of vesicle. The model and current data have been used to
      determine VCE binding constants and protein-to-lipid binding ratios. The model
      predicts that higher lipid affinity (K(B)), protein-lipid binding ratio (n), and
      lower protein concentration result in a shift of the binding isotherm toward a
      lower concentration range of vesicle. A higher vesicle mobility, reflecting the
      size and charge of the vesicle, results in a larger separation window between the
      migration time of the free protein and the complex. The value of VCE for
      structure-function studies and drug design for peptides and proteins that are
      strongly bound to lipids has been illustrated.

PMID- 14708794
TI  - An amperometric detector formed of highly dispersed Ni nanoparticles embedded in
      a graphite-like carbon film electrode for sugar determination.
AB  - We achieved improved detection limits for sugars by developing a novel thin film
      containing 0.8% highly dispersed Ni nanoparticles in disordered graphite-like
      carbon (Ni-NDC) as a detection electrode for high-performance liquid
      chromatography. The Ni-NDC film was prepared in one step by a simple radio
      frequency (rf) sputtering method at a temperature below 200 degrees C. We
      characterized the film by XPS, TEM, and AFM analysis and found that the average
      Ni nanoparticle size was 3 nm and that the film consisted of a mixture of Ni,
      NiO, Ni2O3, and Ni(OH)2. We studied the electrochemical detection of sugars using
      the 0.8% Ni-NDC film electrode. The film electrode had excellent electrocatalytic
      ability and good stability compared with a Ni-bulk electrode with regard to the
      electrooxidation of sugars. We employed the Ni-NDC film as an HPLC detection
      electrode. We achieved a good separation of four sugars (glucose, fructose,
      sucrose, lactose) at a relatively low constant detection potential (0.40 V vs
      Ag/AgCl) and a linearity of over 3 orders of magnitude. We obtained improved
      detection limits for the investigated sugars, namely, 20, 25, 50, and 37 nM for
      glucose, fructose, sucrose, and lactose, respectively. This is at least 1 order
      of magnitude lower than the detection limits obtained with a Ni-bulk electrode
      with the same measurement condition. The Ni-NDC film electrode also showed good
      reproducibility with a relative standard deviation of 1.75% for 40 consecutive
      injections of glucose in a flow system.

PMID- 14708796
TI  - Fluidic preconcentrator device for capillary electrophoresis of proteins.
AB  - A new preconcentration device was developed for analysis of proteins by capillary
      electrophoresis (CE). The microfluidic device uses an electric field to capture
      proteins that pass through the system. The capture zone is maintained in the flow
      stream by the interaction between hydrodynamic and electrical forces. The device
      consists of a flow channel made of PEEK tubing with two electrical junctions,
      each of which is covered with a conductive membrane. A syringe pump provides the
      flow stream and also allows the injection of up to 13.5 microL of a dilute
      sample. The system can be easily connected to a CE device postcapture for off
      line preconcentration of proteins. For the proteins used in this study,
      preconcentration factors up to 40-fold can be achieved. CE detection limits for
      bovine carbonic anhydrase, alpha-lactalbumin and beta-lactoglobulins A and B were
      in the nanomolar range using UV detection at 200 nm. Preconcentration is
      dependent on both time and initial protein concentration. We show the possibility
      of using an off-line fluidic preconcentrator device employing counterflow
      capillary electrophoresis with minimum sample manipulation, achieving detection
      limits similar to on-line approaches.

PMID- 14708797
TI  - A microfluidic electrocapture device in sample preparation for protein analysis
      by MALDI mass spectrometry.
AB  - The design and operation of a microfluidic device for sample preparation in MALDI
      mass spectrometry of peptides and proteins is described. It is particularly
      useful for proteomics applications and for mass determination of proteins in salt
      and detergent-containing solutions. The system consists of a flow channel with
      two conductive areas or electrical junctions where proteins and peptides are
      retained by means of an electric field. The microfluidic device is made of PEEK
      tubing, and the junctions are covered with a conductive polymeric membrane. A
      syringe pump connected to the device produces a flow stream, and injection of
      sample is carried out manually via hydrodynamic pressure. Proteolytic peptides
      and intact proteins in salt- and detergent-containing acidic media were captured
      at the cathode junction followed by exchange of the original solution to a
      solvent suitable for subsequent mass spectrometry. Using this principle, a
      significant desalting effect was obtained for tryptic peptides in mass-mapping
      experiments. Protein sequence coverages were high (up to 40%) at subpicomole
      levels with results better than those obtained using reversed-phase solid-phase
      extraction. In contrast to the latter technique, the microfluidic device has the
      capacity to efficiently remove detergents such as CHAPS before peptide mapping
      and protein analysis.

PMID- 14708798
TI  - Separation of recombinant human erythropoietin glycoforms by capillary
      electrophoresis using volatile electrolytes. Assessment of mass spectrometry for
      the characterization of erythropoietin glycoforms.
AB  - The separation of the glycoforms of erythropoietin (EPO) by capillary
      electrophoresis (CE) was recently published as a monograph by the European
      Pharmacopoeia (European Pharmacopoeia 4 2002, 1316, 1123-1128). Although the
      experimental CE conditions employed a background electrolyte containing additives
      suitable for on-line UV-absorption detection, they were not appropriate for on
      line mass spectrometry (MS) detection. In this work, an attempt was made to
      investigate experimental conditions employing volatile electrolyte systems to
      achieve the separation and characterization of EPO glycoforms using CE and ESI-MS
      methodologies. The influence of several operating conditions, such as the coating
      of the internal walls of the capillary as well as the composition, concentration,
      and the pH of the separation buffer were investigated. The results demonstrated
      that when the internal walls of the capillaries were permanently coated with
      Polybrene and a buffer electrolyte containing 400 mM of HAc-NH4Ac (acetic acid
      ammonium acetate), pH 4.75, was used, a significantly reproducible separation was
      achieved for EPO glycoforms. Intact EPO was characterized by two mass
      spectrometry techniques: electrospray ionization (ESI-MS) and matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF-MS). The data demonstrated
      that MALDI-TOF-MS provided a good approximation to an average molecular mass of
      the EPO molecule. However, it was still necessary to carry out further separation
      of the intact EPO glycoforms in order to obtain molecular mass information when
      ESI-MS was used.

PMID- 14708800
TI  - On-line preconcentration prior to on-column derivatization monolith
      octadecasiloxane capillary electrochromatography for the determination of
      biogenic amines.
AB  - To expand the applications of the on-line preconcentration technique with
      capillary electrochromatography (CEC) to biogenic amines that have no specific
      chromophore or fluorophore in their molecules, a method of on-line
      preconcentration prior to on-column derivatization CEC is presented. A monolithic
      ODS capillary column (20 cm effective length x 75 microm i.d.) for CEC was
      fabricated using a thermal sol-gel reaction of tetraethyl orthosilicate to
      capture ODS particles (5-microm particle diameter) in a capillary tube. A
      standard model biogenic amine solution consisting of histamine, methylhistamine,
      and serotonin was electrokinetically injected from the anodic site of the
      capillary column with 5 kV, and these amines were effectively concentrated at the
      inlet site of the capillary column by a field-amplified sample stacking, a
      gradient effect mode, or both. This preconcentration occurred whenever the
      several types of solvent for reconstitution of the amines, e.g., water
      (noneluting solvent or low-conductivity solvent), 0.9% sodium chloride
      (noneluting solvent or high-conductivity solvent), or 60% acetonitrile in 10 mM
      borate buffer (pH 10) (eluting solvent) were employed. After concentration, the
      amines were subsequently derivatized, separated, and detected during CEC with an
      optimum CEC run buffer solution containing 60% acetonitrile in 5 mM o
      phthalaldehyde/2-mercaptoethanol-10 mM borate buffer (pH 10) when 5 kV was
      continuously applied. Using the present system, equipped with a fluorescence
      detector instead of a UV/visible detector, the detection sensitivity for amines
      reached a 0.1 microM level, which increased sensitivity by a factor of 10(3)
      times greater than that of normal on-column derivatization CEC.

PMID- 14708808
TI  - Acute myocardial infarction: disposition to the operating room?
AB  - Given their low incidence, mechanical complications of AMI represent a diagnostic
      and therapeutic challenge for the EP. When the panoply of medical interventions
      has reached its limitation, surgical treatment plays a role in the management of
      the patient who has AMI. For patients who have CS and severe compromise of
      myocardial reserve, surgical intervention might represent the only means of
      restoring blood flow to the myocardium. For patients who have mechanical
      complications, correction of the defect before the onset of terminal organ
      failure might provide long-term survival.

PMID- 14708809
TI  - The vasculopathic patient: uncommon surgical emergencies.
AB  - Recognition of the patient who has an emergent vascular disorder and the early
      initiation of simple management steps in the ED can significantly impact patient
      outcome. The vasculopathic patient presents with significant comorbid conditions
      and a small window of opportunity to alter the prognosis favorably. The critical
      role of the EP lies in prompt use of this opportunity and appropriate direction
      of further care.

PMID- 14708810
TI  - Aortic emergencies.
AB  - Prompt recognition of actual or impending aortic emergencies is essential to the
      effective practice of emergency medicine. Understanding the pathophysiologic
      principles and awareness of the potential subtleties in the clinical
      presentations of aortic dissection, aneurysm, and occlusive disease are
      prerequisites to this task. Knowledge of current diagnostic modalities is also
      important if these entities are to be identified rapidly and managed efficiently
      to maximize the potential for a good patient outcome. Awareness of the potential
      complications of these conditions and the necessary interventional and
      resuscitative measures that might be called for in the appropriate clinical
      setting are likewise essential requirements for the EP. Appropriate surgical
      consultation and mobilization of operative resources form the backbone of
      appropriate management in the patient who has an aortic emergency.

PMID- 14708811
TI  - The acute cerebrovascular event: surgical and other interventional therapies.
AB  - Over the next decade, more early and aggressive treatments will become available
      for acute stroke. As EPs have been forced to push their skills and knowledge
      significantly further with the advent of time-sensitive interventions for
      myocardial ischemia, a similar sophistication will undoubtedly emerge in the
      management of acute stroke. Certain components of the neurological examination
      will likely assume a new significance and, as with the renewed focus on the
      nature of ST segment change on the ECG in ACS, there will be new attention to
      early imaging findings in stroke. Although it is unclear whether the balance of
      future advances in treatment will come from the world of neurosurgery, neurology,
      or interventional radiology, the EP is relatively assured to play a central role
      in their implementation.

PMID- 14708812
TI  - Surgical complications of selected gastrointestinal emergencies: pitfalls in
      management of the acute abdomen.
AB  - Complaints referable to the abdomen are common emergency department
      presentations. Many of these conditions prove to be benign and self-limited,
      whereas others are potentially catastrophic. Because serious and benign intra
      abdominal conditions share many relatively nonspecific symptoms, it is often
      difficult to identify patients who have life-threatening problems early in the
      course of their disease. Apart from relieving the patient's symptoms, the
      emergency physician's primary role is to detect and stabilize life-threatening
      conditions in a rapid and cost-effective manner.

PMID- 14708813
TI  - Abdominal surgical emergencies in infants and young children.
AB  - Surgical emergencies can be missed easily in children, who are not always able to
      volunteer relevant information. Awareness of the entities discussed in this
      review might help the EP uncover subtle clues to early diagnoses that might not
      be initially apparent. Ill-appearing children who have abdominal pain and
      vomiting should be considered to have ischemic or necrotic bowel until proven
      otherwise. Possible diagnoses include volvulus, intussusception, and necrotizing
      enterocolitis. Bilious vomiting, especially in a young infant, should be
      considered to be an indication of a high bowel obstruction such as midgut
      volvulus, which warrants immediate surgical consultation. Significant rectal
      bleeding with abdominal pain can result from intussusception, volvulus, or an
      inflamed Meckel's diverticulum. Rectal bleeding with unstable vital signs can
      result from an upper GI bleed (eg, peptic ulcer disease). Painless rectal
      bleeding can result from a Meckel's diverticulum, polyps, arteriovenous
      malformation, or a tumor. Examination of the genitalia is imperative, especially
      in boys, to exclude the possibility of an incarcerated hernia or testicular
      torsion.

PMID- 14708814
TI  - Abdominal surgical emergencies in the elderly.
AB  - The evaluation of abdominal pain can be considerably more challenging in elderly
      patients. A higher likelihood of life-threatening pathology combined with a
      myriad of diagnostic pitfalls in this population mandate a more cautious approach
      with greater use of diagnostic resources and specialist consultation.

PMID- 14708815
TI  - Nontraumatic abdominal surgical emergencies in the pregnant patient.
AB  - Although most EPs are aware of the diverse presentations of ectopic pregnancy,
      this diagnosis remains a formidable challenge in the ED. The diagnosis of
      abdominal surgical emergencies in pregnant patients continues to challenge EPs,
      surgeons, and obstetricians alike. Understanding how the gravid state can obscure
      common conditions such as appendicitis, cholecystitis. bowel obstruction, and
      adnexal torsion might help the EP identify suspicious cases early, preventing
      serious consequences to the mother and fetus.

PMID- 14708816
TI  - The AIDS patient with abdominal pain: a new challenge for the emergency
      physician.
AB  - As the prevalence of HIV infection continues to increase, EPs will be called upon
      to evaluate increasing numbers of AIDS patients who have abdominal pain, some of
      whom will require emergent surgical intervention. In addition to the myriad
      causes of abdominal pain in the nonimmunocompromised patient, the differential
      diagnosis in the AIDS patient includes a wide variety of opportunistic infections
      and neoplasms (Table 5). Evaluation frequently requires extensive laboratory
      studies and cultures and advanced imaging (CT, ultrasound, and so forth). A low
      threshold for surgical and other subspecialty consultation should be in place
      because of the often subtle presentation of surgical emergencies in AIDS
      patients.

PMID- 14708817
TI  - Gastrointestinal hemorrhage: is the surgeon obsolete?
AB  - The management of GI hemorrhage has undergone tremendous evolution in recent
      decades. Once commonly managed by surgeons, the almost continuous introduction of
      new technologies and pharmacotherapies has dramatically improved clinicians'
      ability to identify and control sources of bleeding without surgery. Although a
      gastroenterologist can successfully manage most cases of GI hemorrhage
      endoscopically, surgical consultation remains an important consideration for the
      emergency physician in selected cases.

PMID- 14708818
TI  - Emergent surgical complications of genitourinary infections.
AB  - The entities described in this article represent processes that arise from, or
      can be mistaken for, common GU infections. It might be difficult to determine the
      point at which pyelonephritis develops into EPN or perinephric abscess. It might
      be equally challenging to distinguish scrotal cellulitis from Fournier's
      gangrene; however, as most EPs will acknowledge, the mere awareness of these
      entities in the appropriate clinical circumstances might be enough to prevent a
      "near-miss" of a surgical emergency.

PMID- 14708819
TI  - Necrotizing soft-tissue infections.
AB  - It has been more than 130 years since NSTIs were first described. Despite the
      development of various classification systems and progress in surgical
      management, these infections continue to have high mortality and pose enormous
      diagnostic and therapeutic challenges. For optimal outcome, treatment involves
      rapid institution of appropriate antibiotic coverage and early wide surgical
      debridement. Recovery requires aggressive resuscitation, postoperative
      nutritional support and wound care that is similar to the care of burn patients
      in many respects. The entire therapeutic process requires a well-prepared and
      coordinated team of health care professionals including EPs, general, orthopedic,
      and other specialist surgeons, infectious disease consultants, specially trained
      nursing staff, and physical therapists.

PMID- 14708820
TI  - Surgical emergencies in the intravenous drug user.
AB  - Numerous surgical complications arise from parenteral drug use. Some
      complications have severe sequelae and most prove to be a diagnostic challenge.
      It is likely that these problems will remain a significant burden on the health
      care system as a result of continued widespread drug abuse. EPs must always
      maintain vigilance when evaluating medical complaints in the IVDU.

PMID- 14708821
TI  - Surgical issues in the poisoned patient.
AB  - Some toxicologic emergencies require immediate or urgent surgical intervention in
      addition to routine medical care. The EP must be familiar with the indications
      for operative care, even though many of these poisonings and exposures are
      relatively rare. The EP must also be knowledgeable regarding the various means of
      surgical decontamination that are available, including temporary cardiopulmonary
      bypass. Finally, a high level of vigilance must be maintained for patients who
      have delayed presentation and fulminant organ failure necessitating early
      involvement of the transplantation team.

PMID- 14708822
TI  - Occult trauma in high-risk populations.
AB  - Several groups of patients are at increased risk for traumatic injury that is
      "occult," or not apparent on initial presentation. Perhaps the most notorious are
      those who abuse alcohol, but other groups include the elderly, coagulopathic,
      those with neurological disease, and the mentally ill. Moreover, traumatic injury
      can coexist with (or be masked by) medical pathology, resulting in the
      disposition of injured patients to nonsurgical services where surveillance for
      traumatic injury diminishes. Because delays or failures in diagnosis might result
      in unnecessary pain, morbidity, and mortality, it is important for the emergency
      physician to identify occult presentations of trauma before disposition. This
      review highlights commonly missed traumatic injuries in adult patients.

PMID- 14708823
TI  - Surgical management and strategies in the treatment of hypothermia and cold
      injury.
AB  - Increased participation in outdoor activities and the epidemic of homelessness
      have caused the incidence of cold injuries in the civilian population to rise
      dramatically over the last 20 years. Knowledge of the treatment is crucial for
      emergency physicians in rural and urban areas. Recent developments have
      significantly advanced the understanding of the pathophysiology of hypothermic
      and frostbite injuries. Together with improved rewarming techniques and use of
      radiological assessment of tissue viability, future advancements should allow for
      a more aggressive and active approach to the management of these injuries.

PMID- 14708824
TI  - Chronic inflammatory demyelinating polyneuropathy after initiation of peritoneal
      dialysis--a distinct clinical entity?

PMID- 14708825
TI  - Transplanting solid organs from HBsAg negative donors positive for antibody to
      hepatitis B core antigen: the implications.

PMID- 14708826
TI  - Continuous flow peritoneal dialysis: a new double lumen catheter.
AB  - Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in
      the sixties. It was then abandoned because of technical reasons, but, today, a
      new interest in this technique is emerging, because of new technical solutions
      and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a
      certain amount of fluid is maintained in the peritoneal cavity, while a
      continuous inflow and outflow is provided via twin catheters or through a double
      lumen catheter. In this paper a new double lumen catheter is presented. The
      catheter is characterized by the presence of a diffuser in the inflow lumen,
      while a standard coiled shape characterizes the outflow lumen. The diffuser
      allows the use of high dialysate flows without peritoneal damage and with an
      excellent distribution of the fluid. The other feature of the catheter is the
      removable hub which allows for an easy subcutaneous tunneling of the catheter
      with a subsequent connection to the y segment. The special shape also guarantees
      a minimum recirculation during treatment. Data obtained in the first implanted
      catheter showed a progressive increase in small solute clearances in relation to
      an increase of the flow and the tidal volume in the peritoneal cavity. In
      particular, urea clearances up to 48 ml/min and creatinine clearances up to 39
      ml/min were obtained. No major complications were observed after one year of use
      of the catheter.

PMID- 14708827
TI  - Chronic hemodialysis in a Nigerian teaching hospital: practice and costs.
AB  - The incidence of end-stage renal disease (ESRD) is on the rise in developing
      countries. To identify issues related to renal replacement therapy in ESRD
      patients in the developing world, we analyzed the practice and costs of
      hemodialysis in Nigerian ESRD patients. Ten ESRD patients were dialyzed at the
      Jos University Teaching Hospital, Jos, Plateau State, Nigeria, between June 15
      and July 15, 2003. In these patients, we analyzed initiation, vascular access
      issues, frequency, duration, adequacy and economics of chronic hemodialysis. The
      Nigerian patients were referred to the nephrologist for the first time only when
      they had developed frank uremia. No patient had a permanent vascular access at
      the time dialysis was initiated. Only two patients had a functioning dialysis
      fistula, while the other eight patients were dialyzed through temporary femoral
      vein catheters that were removed after each dialysis. Frequency of dialysis was
      three times weekly in 2 patients, twice weekly in 1 patient and once weekly or
      less frequently in 7 patients. The duration of a dialysis session was prescribed
      to be 4 hours, but sessions often lasted for as long as 10 hours because of
      breakdowns of the antiquated dialysis machines. The urea reduction ratio was 45.3
      +/- 8.6%. In every case, the cost of dialysis was borne by the patients and their
      families. Comparison of the cost of dialysis, with extensive re-use of supplies,
      to monthly incomes of Nigerians with different professions revealed that the
      great majority of Nigerians cannot afford three times weekly dialysis.
      Underdialysis in Nigerian ESRD patients is common and caused by socioeconomic
      factors and technologic deficits. One step towards correction of underdialysis
      could be sharing of the cost of dialysis by the public.

PMID- 14708828
TI  - Seasonal variations of chronic hemodialysis dose in South Croatia.
AB  - INTRODUCTION: The dialysis parameters are used for prescribing the dose of
      dialysis therapy. Delivered dialysis dose could be calculated from predialysis
      and postdialysis blood urea concentrations. Seasonal variations in some clinical
      and laboratory variables occur among chronic hemodialysis patients. Seasonal
      variations in chronic hemodialysis dose have not been investigated. We
      prospectively compared hemodialysis adequacy parameters in order to demonstrate
      its seasonal differences. SUBJECTS AND METHODS: Data were processed on 201 single
      dialysis treatments involving a group of 51 anuric chronic hemodialysis patients.
      The study period was 12 months. Four measurements per subject were obtained (in
      January, April, July, and October). RESULTS: We could not demonstrate seasonal
      variability in prescribed and delivered hemodialysis dose, in "delta" values
      (absolute differences between prescribed and delivered dialysis doses for the
      same hemodialysis treatment), or in ultrafiltration per hemodialysis. Seasonal
      differences were found in blood urea concentrations before and after hemodialysis
      (p = 0.001, p = 0.010). When the data were grouped into two groups: cold (January
      and October) and mild (April and July) months; we could not demonstrate
      significant differences in dialysis adequacy parameters, but there were
      differences in blood urea concentration before hemodialysis (26.06 +/- 14.73 vs.
      24.35 +/- 4.50, p = 0.004), blood urea concentration alter hemodialysis (10.24 +/
      2.96 vs. 9.43 +/- 2.60, p = 0.019), and ultrafiltration per hemodialysis (3.36
      +/- 1.13 vs. 3.10 +/- 1.11, p = 0.046). CONCLUSION: Based of the results of this
      investigation conducted on chronically hemodialyzed patients in the mild
      Mediterranean climate in South Croatia, Europe; we have concluded that clinicians
      should not pay attention to season when they prescribe hemodialysis dose or
      analyze delivered hemodialysis dose.

PMID- 14708829
TI  - Effects of dialyzer membrane on serum albumin levels in patients receiving
      hemodialysis.
AB  - Biocompatibility of the dialyzer membrane has been thought to affect the
      nutritional status in patients receiving chronic hemodialysis. In a series of
      patients treated in an outpatient dialysis unit, serum albumin was measured
      before and after changing the dialyzer membrane from one of cellulose to one of
      polysulfone. There were 48 patients (25 men and 23 women) who had been on
      dialysis for a mean duration of 78.6 months. The follow-up period was at least 6
      months for each type of membrane. Delivered dose of dialysis was higher using the
      polysulfone membrane but serum albumin was not affected by a change to the more
      biocompatible membrane. Nutritional considerations are not important in choosing
      a membrane for dialysis.

PMID- 14708830
TI  - Numerical simulation of a realistic total cavo-pulmonary connection: effect of
      unbalanced pulmonary resistances on hydrodynamic performance.
AB  - Total cavo pulmonary connection (TCPC) is one of the surgical techniques adopted
      to compensate the failure of the right heart in pediatric patients. The main goal
      of this procedure is the realization of a configuration for the caval veins and
      for the pulmonary arteries that can guarantee as low as possible pressure losses
      and appropriate lung perfusion. Starting from this point of view, a realistic
      TCPC with extracardiac conduit (TECPC) is investigated by means of Computational
      Fluid Dynamics (CFD) to evaluate the pressure loss under different pressure
      conditions, simulating different vessel resistances, on the pulmonary arteries. A
      total flow of 3 L/min, with a distribution between the inferior vena cava (IVC)
      and the superior vena cava (SVC) equal to 6/4, was investigated; three different
      boundary conditions for the pressure were imposed, resulting in three simulations
      in steady-state conditions, to the right pulmonary artery (RPA) and to the left
      pulmonary artery (LPA), simulating a balanced (deltaP(LPA-RPA) = 0 mmHg) and two
      unbalanced pulmonary resistances to blood flow (a pressure difference deltaP(LPA
      RPA) = +/- 2 mmHg, respectively). The geometry for the TECPC was realized
      according to MRI derived physiological values for the vessels and for the
      configuration adopted for the anastomosis (the extra-cardiac conduit was inclined
      22 degrees towards the left pulmonary artery with respect to the IVC axis). The
      computed power losses agree with previous in vitro Particle Image Velocimetry
      investigations. The results show that a higher resistance on the LPA causes the
      greater pressure loss for the TECPC under study, while the minimum pressure loss
      can be achieved balancing the pulmonary resistances, subsequently obtaining a
      balanced flow repartition towards the lungs.

PMID- 14708831
TI  - Design of a continuous flow centrifugal pediatric ventricular assist device.
AB  - Thousands of pediatric patients suffering from cardiomyopathy or single
      ventricular physiologies secondary to debilitating heart defects may benefit from
      long-term mechanical circulatory support due to the limited number of donor
      hearts available. This article presents the initial design of a fully implantable
      centrifugal pediatric ventricular assist device (PVAD) for 2 to 12 year olds.
      Conventional pump design equations, including a nondimensional scaling approach,
      enabled performance estimations of smaller scale versions (25 mm and 35 mm
      impeller diameters) of our adult support VAD. Based on this estimated
      performance, a computational model of the PVAD with a 35 mm impeller diameter was
      generated. Employing computational fluid dynamics (CFD) software, the flow paths
      through the PVAD and overall performance were analyzed for steady state flow
      conditions. The numerical simulations involved flow rates of 2 to 5 LPM for
      rotational speeds of 2750 to 3250 RPM and incorporated a k-epsilon fluid
      turbulence model with a logarithmic wall function to characterize near-wall flow
      conditions. The CFD results indicated best efficiency points ranging from 25% to
      28%, which correlate well with typical values of blood pumps. The results further
      demonstrated that the pump could deliver 2 to 5 LPM at 70 to 95 mmHg for desired
      physiologic conditions in resting 2 to 12 year olds. Scalar stress levels
      remained below 300 Pa, thereby signifying potentially low levels of hemolysis.
      Several flow regions in the pump exhibited signs of vortices, retrograde flow,
      and stagnation points, which require optimization and further study. This CFD
      model represents a reasonable starting point for future model enhancements,
      leading to prototype manufacturing and experimental validation.

PMID- 14708832
TI  - Pilot study on prevention of lung injury during surgery for type A acute aortic
      dissection: no evident improvements with celsior flushing through the pulmonary
      artery.
AB  - OBJECTIVE: Postoperative respiratory failure is a frequent and serious
      complication in patients with type A acute aortic dissection. Experimental
      evidence suggests that pulmonary artery perfusion using hypothermic protective
      solutions helps prevent lung injury. The aim of this pilot prospective study was
      to evaluate the effect of pulmonary artery flushing during selective cerebral
      perfusion (SCP) on lung function. METHODS: Twenty patients referred for acute
      type A aortic dissection, who were free from preoperative respiratory
      dysfunction, were assigned prospectively and alternately to two treatment groups.
      Pulmonary flushing was performed during SCP in group P (10 patients), while
      conventional Kazui technique was applied in group N (10 patients). Lung perfusion
      consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung
      function was evaluated by intubation time, scoring of chest radiograms at 12
      hours after CPB, and PaO2/FiO2 assessed from immediately before surgery to 72
      hours after termination of cardiopulmonary bypass. RESULTS: Incidence of pre,
      intra and post operative determinants of lung dysfunction proved homogeneous in
      both groups. Lung oxygenation function showed a marked post operative decline
      followed by a slow improvement in both groups. Analysis of respiratory ratios did
      not disclose significant differences even though the flushed group had a better
      performance in all study patients. The incidence of prolonged ventilator support
      (longer than 72 hours) (30% vs 20%, p = NS) and severity of x-ray pulmonary
      infiltrate score were comparable (mean score 1.7 +/- 0.71 vs 1.6 +/- 0.68, p =
      NS). CONCLUSIONS: Pulmonary artery flushing with Celsior solution does not seem
      to provide an effective preservation of lung function.

PMID- 14708833
TI  - Effect of lipoprotein apheresis on oxidative stress and antioxidant status in
      familial hypercholesterolemic patients.
AB  - Extracorporeal low-density lipoprotein (LDL) apheresis is an established and
      highly effective therapy for the patients with familial hypercholesterolemia (FH)
      not adequately responding to diet and drug therapy alone. This study was designed
      to measure the effect of lipid apheresis on oxidant and antioxidant status in a
      patient with FH. The levels of plasma lipid peroxidation were determined as
      thiobarbituric acid-reactive substances. The activities of the antioxidant
      enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GPx) were established in one subject with FH before and after lipid apheresis.
      The pre- and post lipid apheresis procedures witness a significant decrease in
      oxidative stress (p < 0.05) but the erythrocyte levels of CAT, SOD and GPx were
      unchanged.

PMID- 14708834
TI  - The special problems of adolescents.

PMID- 14708835
TI  - Development of a speech-in-multitalker-babble paradigm to assess word-recognition
      performance.
AB  - A simple word-recognition task in multitalker babble for clinic use was developed
      in the course of four experiments involving listeners with normal hearing and
      listeners with hearing loss. In Experiments 1 and 2, psychometric functions for
      the individual NU No. 6 words from Lists 2, 3, and 4 were obtained with each word
      in a unique segment of multitalker babble. The test paradigm that emerged
      involved ten words at each of seven signal-to-babble ratios (S/B) from 0 to 24
      dB. Experiment 3 examined the effect that babble presentation level (70, 80, and
      90 dB SPL) had on recognition performance in babble, whereas Experiment 4 studied
      the effect that monaural and binaural listening had on recognition performance.
      For listeners with normal hearing, the 90th percentile was 6 dB S/B. In
      comparison to the listeners with normal hearing, the 50% correct points on the
      functions for listeners with hearing loss were at 5 to 15 dB higher signal-to
      babble ratios.

PMID- 14708836
TI  - Distortion product otoacoustic emissions: comparison of sequential versus
      simultaneous presentation of primary-tone pairs.
AB  - This Grason-Stadler GSI-60 system for measuring distortion product otoacoustic
      emissions (DPOAEs) allows the examiner to present one set of primary-tone pairs
      at a time (i.e., sequential presentation), or to present as many as four sets of
      primary-tone pairs at a time (i.e., simultaneous presentation). The Sequential
      and Simultaneous protocols were used to compare administration times, DPOAEs, and
      noise floors (NFs) on normal-hearing subjects at three frequencies (f2 = 1000,
      2000, and 4000 Hz) and eight intensities (L1 = 40-75 dB SPL in 5 dB steps; L2 =
      30-65 dB SPL). The Simultaneous protocol was completed in less than half the time
      (mean = 2 minutes, 21 seconds) required for the Sequential protocol (mean = 5
      minutes, 13 seconds). When stimulus intensity (L1) was <60 dB SPL, the Sequential
      and Simultaneous protocols yielded similar DPOAEs and NFs. However, at the higher
      L1 intensities, the NFs for the Simultaneous protocol were larger than those for
      the Sequential protocol. The higher Simultaneous NFs reflect the greater system
      distortion/noise generated by the GSI-60 instrumentation. Reliability was
      assessed using the standard error of measurement of the difference between two
      scores. The data revealed no significant differences between protocols, and
      suggest that differences between two DPOAEs are statistically significant if they
      exceed approximately 7 dB (95% confidence interval).

PMID- 14708837
TI  - Counseling adolescents with hearing loss with the use of self
      assessment/significant other questionnaires.
AB  - After adapting a pair of adult Self-Assessment/Significant Other questionnaires,
      the first author explored the value of the modified questionnaires in providing
      counseling to adolescents with hearing loss. Twenty adolescents with hearing loss
      served as subjects; peers with normal hearing were selected as their Significant
      Other to capitalize on the importance of peer relationships and opinions during
      adolescence. Each dyad completed a 12-item questionnaire designed to explore the
      communicative, emotional, and social impact of hearing loss. Responses to each
      pair of questionnaires were reviewed by the adolescent and the audiologist and
      served as a basis for counseling. Subsequent dialogues revealed recurring themes
      as the teens attempted to face age-appropriate developmental challenges as
      individuals with hearing loss. Based on their responses to a follow-up
      questionnaire, most of the adolescents found the counseling process beneficial.

PMID- 14708838
TI  - The effects of click and tone-burst stimulus parameters on the vestibular evoked
      myogenic potential (VEMP).
AB  - Vestibular evoked myogenic potentials (VEMP) are short latency electromyograms
      (EMG) evoked by high-level acoustic stimuli and recorded from surface electrodes
      over the tonically contracted sternocleidomastoid (SCM) muscle and are presumed
      to originate in the saccule. The present experiments examined the effects of
      click and tone-burst level and stimulus frequency on the latency, amplitude, and
      threshold of the VEMP in subjects with normal hearing sensitivity and no history
      of vestibular disease. VEMPs were recorded in all subjects using 100 dB nHL click
      stimuli. Most subjects had VEMPs present at 500, 750, and 1000 Hz, and few
      subjects had VEMPs present at 2000 Hz. The response amplitude of the VEMP
      increased with click and tone-burst level, whereas VEMP latency was not
      influenced by the stimulus level. The largest tone-burst-evoked VEMPs and lowest
      thresholds were obtained at 500 and 750 Hz. VEMP latency was independent of
      stimulus frequency when tone-burst duration was held constant.

PMID- 14708839
TI  - Unilateral hearing loss in children with shunt-treated hydrocephalus.
AB  - This study investigated the characteristics of hearing loss in children with
      ventriculoperitoneal (VP) shunted hydrocephalus. Twelve hydrocephalic children
      with patent VP shunts participated. The etiology of the hydrocephalus was either
      intraventricular hemorrhage or spina bifida. Audiometric examination included
      pure-tone air conduction thresholds, tympanometry, contralateral and ipsilateral
      acoustic reflex thresholds (ARTs), and distortion product otoacoustic emissions
      (DPOAEs). A unilateral, high-frequency, cochlear hearing loss was found in the
      ear ipsilateral to the shunt placement in 10 (83%) of the 12 shunt-treated
      hydrocephalic children. No hearing loss was observed in the ear contralateral to
      shunt placement. Based on the pure-tone audiometric findings, coupled with the
      decrease in DPOAE amplitude in the shunt ear, the hearing loss appears to be
      cochlear in nature. We suggest that cochlear hydrodynamics are disrupted as the
      result of reduced perilymph pressure, a consequence of cerebrospinal fluid (CSF)
      reduction due to the combined effects of a patent shunt and a patent cochlear
      aqueduct. In addition, a concomitant brain stem involvement is evidenced in the
      ART pattern, possibly produced by the patent shunt draining the CSF from the
      subdural space, resulting in cranial base hypoplasia.

PMID- 14708840
TI  - Acoustic hemifields in the spatial release from masking of speech by noise.
AB  - The Hearing-in-Noise Test (HINT) is able to measure the benefit to speech
      intelligibility in noise conferred when the noise masker is displaced 90 degrees
      in eccentricity from a speech source located at zero degrees azimuth. Both
      psychoacoustic and neurophysiological data suggest that the perceptual benefit of
      the 90-degree azimuth separation would be greatest if the speech and noise were
      presented in different acoustic hemifields, and would be smallest if the two
      sources were in the same acoustic hemifield. The present study tested this
      hypothesis directly in ten normal-hearing adult listeners. Using the HINT
      stimuli, we confirmed the hypothesis. Release from masking scores averaged 8.61
      dB for "between-hemifield" conditions, 6.05 dB for HINT conditions, and 1.27 dB
      for "within-hemifield" conditions, even though all stimulus configurations
      retained a 90-degree angular separation of speech and noise. These data indicate
      that absolute separation of speech and noise alone is insufficient to guarantee a
      significant release from masking, and they suggest that what matters is the
      location of the stimulus elements relative to the left and right spatial
      perceptual channels.

PMID- 14708841
TI  - The effects of high-frequency hearing loss on low-frequency components of the
      click-evoked otoacoustic emission.
AB  - Click-evoked otoacoustic emission (CEOAE) input/output (I/O) functions were
      measured in ears with normal hearing and in ears with sensorineural hearing loss
      above 2000 Hz. The low- to midfrequency CEOAEs obtained from the ears with high
      frequency hearing loss were significantly reduced in level compared to the CEOAEs
      obtained from the ears with normal hearing even though there were no significant
      group differences in the 250-2000 Hz pure-tone thresholds. The findings are
      discussed within the context of two hypotheses that explain the low- to
      midfrequency reduction in transient-evoked otoacoustic emission (TEOAE)
      magnitude: (1) subclinical damage to the more apical regions of the cochlea not
      detected by behavioral audiometry, or (2) trauma to the basal region of the
      cochlea that affects the generation of low-frequency emissions. It is proposed
      that localized damage at basal cochlear sites affects the generation of low- to
      midfrequency CEOAE energy.

PMID- 14708842
TI  - Strongyloidiasis in Sfax (Tunisia): a survey over 13 years period.
AB  - A retrospective study of strongyloidiasis cases was carried out in Sfax
      University (Tunisia), between 1989 and June 2001. Diagnosis was done by direct
      stool examination, concentration methods, Baermann larval extraction and fecal
      culture. Strongyloidiasis was diagnosed in 27 patients of whom 77% were males
      living in rural areas under low socioeconomic level. Mean age of patients was 47
      years (8 to 85 years). Hypereosinophilia was present in 75 % of cases, and 7
      patients were treated by systemic corticosteroids. So, it is important to detect
      this parasite by repeated parasitological stool examinations, particularly before
      a long corticosteroid treatment.

PMID- 14708843
TI  - Pancreatitis due to ascaris lumbricoides, a case report.
AB  - Ascaris is the 2nd commonest intestinal parasite world-wide. Although infection
      can pass asymptomatic, some can present with complications. The reported case is
      a Syrian female patient presented with acute on top of chronic pancreatitis due
      to A. lumbricoides. She received Ascaris treatment every 6 months but still
      having eggs in stool due repeated infections.

PMID- 14708844
TI  - Effect of carnosine administration on the immune response of rabbit to
      Schistosoma mansoni antigens.
AB  - SDS-PAGE separation of soluble worm antigen preparation (SWAP), cercarial antigen
      preparation (CAP), and soluble egg antigen (SEA) of Schistosoma mansoni showed
      obvious qualitative and quantitative differences. The shared polypeptides of the
      three stages of S. mansoni were 116, 72.768 and 32.367 kDa under reducing
      conditions. The different anti-sera raised in rabbits against the different
      stages of antigens were recognized by electroimmune transfer blotting (EITB).
      Each of the 3 groups separated eight bands. Carnosine treatment of rabbits
      immunized with SWAP, CAP or SEA resulted in the disappearance of two bands in
      SWAP group and one band in CAP group in comparison with the non-treated immunized
      groups. This indicated that the carnosine modulated immune response of rabbits
      against S. mansoni antigens.

PMID- 14708845
TI  - Suface topography of adult Anchitrema sanguineum (Sansio, 1894) Looss, 1899 and
      Prosthodendrium (Prosthodendrium) urna (Looss, 1907) Dollfus, 1931 infecting bats
      in Upper Egypt (Qena).
AB  - Anchitrema sanguineum and Prosthodendrium (Prosthodendrium) urna are two digenean
      trematodes infecting many species of bats in Egypt. The surface topography of
      them was studied by scanning electron microscopy. Examination of A. sanguineum
      revealed the presence of posteriorly directed broadbase spines allover the body.
      The oral sucker is bordered by several small sucker-like papillae and few
      irregularly distributed pores. The ventral sucker is smaller than the oral one
      and surrounded by several papillae. In P. (P.) urna the body is covered with
      simple, spines posteriorly directed. The oral sucker has few papillae and its
      tegumental rim slightly elevated. The ventral sucker is slightly larger than the
      oral one.

PMID- 14708846
TI  - Re-evaluation of zoonotic cutaneous leishmaniasis status in North Sinai
      Governorate, Egypt.
AB  - Generally speaking, there are at least few endemic zoonotic cutaneous
      leishmaniasis (ZCL) in the Sinai and the Suez Canal Governorates. A spotlight
      survey for new cases of human ZCL among out-patients with skin complaints
      revealed sixteen out of 100 (16%) individuals examined. But, none ZCL infection
      was found among 50 normal individuals. The typing of three human isolates proved
      to be Leishmania major Zymodeme London 70. Trapping and examination of the rodent
      reservoirs and sand-fly vector(s) were carried out as well, but will be published
      later on.

PMID- 14708847
TI  - Morbidity of schistosomiasis mansoni in rural Alexandria, Egypt.
AB  - A parasitological survey of stool and urine of 2577 from 3281 individuals living
      in Abis villages, Alexandria was undertaken in 1998 in order to investigate the
      prevalence of schistosomiasis in this area and risk factors for hepatic
      morbidity. A random sample of 1082 individuals was interviewed using a
      questionnaire regarding risk factors for liver morbidity. All interviewed adults
      (total: 728) were clinically examined for evidence of organomegally
      (hepatomegally and/or splenomegally). Individuals with clinically detected
      organomegally were referred for detailed investigations (total: 65). The criteria
      for severe hepatic morbidity were AST/ALT ratio higher than 1, prothrombin
      activity < 70%, and evidence of portal hypertension. The results revealed that
      prevalence of S. mansoni accounted for 20.5%, with low intensity of infection and
      increased with age to reach a maximum of 40-46.3% at 15-30 years of age.
      Intensity of infection followed the same pattern. All tested urine samples were
      negative for S. haemato-bium. The prevalence of clinically detected organomegally
      was 10.3% among adults (75/728). Significant risk factors for developing
      organomegally were age > or = 35 years (2.2 folds), farming occupation (1.7
      fold), history of parenteral anti-schisto-somal treatment (PAT) with or without
      tablets (2.03 folds), and heavy water canal exposure (2.85 folds). Detailed
      morbidity study on 65 individuals with clinically detected organomegally showed
      that 52.3% reported heavy score for water canal exposure, 33.8% were positive for
      HCV antibodies, and 7.7% for HBV antibodies. Procollagen level was higher than
      5.5 microg/l in 26.2% of this group. The results of Doppler ultrasonography
      showed that 33.3% recorded a portal vein diameter > or = 13 mm, 26.2% periportal
      fibrosis more than grade 2 (> 5 mm), 19% hepatofugal direction of portal blood
      flow, 30.2% collaterals, 28.6% splenomegaly, and 17.5% hepatofugal direction of
      splenic blood flow. The burden of severe hepatic morbidity was alarming among
      this group: 33.8% with portal hypertension, 24.6% with prothrombin activity < 70,
      and 13.8% with AST/ALT ratio > 1. There was a 4.44 and 3.7 fold increased risk
      for portal hypertension with elevated levels of PIIIP and positive serologic
      tests for HCV and/or HBV infections, respectively. Similarly, a 4.58 and 18.35
      fold increased risk for AST/ALT more than one was attributed to these two
      factors, respectively. Elevated procollagen level was significantly associated
      with viral infection (HCV and/or HbsAG). Seropositivity for HCV antibodies was
      found strikingly high in adults above 35 years (positive HCV antibodies in 45.9%
      of individuals). This indicates a high level of endemicity in the study area
      which is also endemic for S. mansoni. So, a heavy burden of severe liver disease
      exist in rural Alexandria is attributed to combined infection of S. mansoni and
      hepatitis viruses. This emphasizes the need for intervenetion strategies
      targeting these two main liver offenders.

PMID- 14708848
TI  - Eimeria gasperettii n. sp. (Apicomplexa: Eimeriidae) from the horned viper,
      Cerates cerastes gasperettii in Saudi Arabia.
AB  - Eimeria gasperettii n. sp. is described from the gall bladder of the horned
      viper, Cerastes cerastes gasperettii from Al-Thumamah, central region of Saudi
      Arabia. Sporulated oocysts are ellipsoid in shape, measuring 38.8 x 25.5 (29-41 x
      17.2-28.4) microm with smooth brownish-yellow bilayered wall, 1.7(1.5-2.0)
      microm.thick. Micropyle polar granule and oocyst residuum are absent. Sporocysts
      are ellipsoid reaching 13.8 x 9.6 (11-14.5 x 8.0-10.3) microm. Sporocyst residuum
      is present. The sporocyst lacks a Stieda body. Sporozoites are crescent-shaped
      blunt at one end and slightly tapered at the other. Eimeria species from
      Viperidae are compared.

PMID- 14708849
TI  - Culicini mosquito larvae in Greater Cairo.
AB  - No doubt, there is a marked civilization and modern establishment of housing,
      agricultural and industrial projects in Egypt. In a survey to evaluate the
      culicini mosquito larvae in Greater Cairo, five species were recovered. These
      were Culex pipiens, Cx. pusillus, Cx. perexiguus Culiseta longia reolata and
      Aedes caspius. The taxonomic features of the larvae were given and illustrated.
      The results were discussed on the light of previous work carried out in Egypt.

PMID- 14708850
TI  - Diagnosis of Fasciola gigantica in snail using the polymerase chain reaction
      (PCR) assay.
AB  - The 124-bp repetitive and highly abundant DNA sequence--used as a specific probe
      for the detection of Fasciola hepatica infection in snails--was tested in the
      detection of F. gigantica infection in Lymnaea natalensis. The probe did not show
      any positive PCR results with Lymnaea natalensis, Physa acuta, Biomphalaria
      alexandrina and Bulinus trucatus or with Schistosoma mansoni, S. haematobium and
      Echinostoma liei. However, the probe was found capable to detect F. gigantica
      infection within L. natalensis at very early stages of the prepatent period and
      at very low concentrations. Thus, the present assay is specific and sensitive for
      the detection of F. gigantica within its intermediate host. It confirmed the idea
      that 124-bp repetitive and highly abundant DNA sequence in Fasciola sp. genome
      could be used as an epidmiological tool for examination of fasciolosis
      intermediate host. The nucleic acid-based assay could eliminate both inherent
      uncertainties and lengthy periods of time required for visual examination of the
      snails. Also, the assay is valuable in epizootiology of F. gigantica, vector
      suitability and host-parasite relationship.

PMID- 14708851
TI  - Difference in the susceptibility to certain molluscicides and Schistosoma mansoni
      infection of three forms Egyptian Biomphalaria glabrata.
AB  - The first generation of 3 morphologically different forms of B. glabrata
      collected from Giza were compared for LC50 values susceptibility to bayluscide
      and copper sulphate (chemical molluscicides) and Anagallis arvensis and Calendula
      micrantha (plant molluscicides) and to Schistosoma mansoni infection. Form (2) as
      juvenile and adult were less sensitive to C. micrantha and A. arvensis. Form (3)
      as juvenile and form (1) as adult were least sensitive to CuSO4. Approximately
      the same susceptibility to bayluscide was observed in the 3 forms either as
      juvenile or adult. The sublethal concentrations of the molluscicides on B.
      glabrata 3 forms showed no significant difference in the growth or survival rate
      in between. Form (2) was significantly higher in the egg lying capacity. The
      total protein concentration was not affected except in certain cases where the
      increase was primarily due to the increase in the globulin concentrations which
      indicate with the marked increase observed in the urea concentration and marked
      increase or inhibition in the activity of either AST or ALT that the digestive
      gland of the 3 forms of snails is seriously affected by molluscicides. The 3
      forms of B. glabrata showed low susceptibility to infection with the local strain
      of S. mansoni.

PMID- 14708852
TI  - Clinical and parasitological studies on the efficacy of Mirazid in treatment of
      schistosomiasis haematobium in Tatoon, Etsa Center, El Fayoum Governorate.
AB  - No doubt, schistosomiasis tops all the endemic parasitic diseases world-wide
      particularly in Egypt. This study evaluated the efficacy of Mirazid (Commiphora
      molmol) in the treatment of parasitologically and clinically and ultrasonography
      confirmed cases of schistosomiasis haematobium in Tatoon village. A sum of 70 out
      of 885 individuals of both sexes (>15 to 60 years old) screened for S.
      haematobium infection were selected. They had light infection (1-10 eggs/10 ml.),
      moderate infection (10-100 eggs/10 ml.) and heavy infection (>100/10 ml.). They
      were subjected to urine and stool analysis, renal function tests, clinical
      examination and abdomino-pelvic ultrasound. They were treated with Mirazid as 10
      mgm/Kg. However, eight of them were unable to swallow the drug. Out of the 62
      schistosomiasis haematobium patients, 57 (91.9%) were cured after two months
      follow up and the cure rate reached 59 (95.2%) on the 3rd month post-Mirazid
      treatment. The cure result was evaluated clinically, parasitologically and
      ultrasonographically. So, Mirazid in a dose of two capsules (600 mgm) on an empty
      stomach before breakfast for six successive days proved to be very effective and
      safe in the treatment of schistosomiasis haematobium.

PMID- 14708853
TI  - On the pathogenicity of attenuated Schistosoma mansoni cercariae released from
      metabolically disturbed Biomphalaria alexandrina.
AB  - Biomphalaria alexandrina were treated with sublethal concentrations (LC10) of dry
      powdered leaves Solanum nigrum or whole dry Ambrosia maritima. The two plants
      affected the development of schistosome parasite within snails by disturbing the
      glycolytic flux, the most important metabolic pathway for schistosome-infected
      snails. Attenuated cercariae released from treated snails were used to infect
      male albino mice to evaluate their pathogenicity compared to control cercariae
      shed from untreated snails. The mean number of worms established declined from
      about 70 +/- 17.6 worms/mouse infected with control cercariae to 23.4 +/- 20.33
      and 14.18 +/- 10.06 worms/mouse infected with S. nigrum and A. maritima
      attenuated cercariae respectively. Most males and females detected in these
      animals measured 0.4-0.6 and 0.6-1.2 mm respectively compared to 1.2-1.4 and 1.4
      1.7 mm in males and females released from mice infected with normal cercariae.
      Egg count in the liver and intestine of mice infected with attenuated cercariae
      was remarkably lower showing reduced fecundity of worms developed from attenuated
      cercariae. Number and size of granulomatous reactions showed remarkable reduction
      in attenuated cercariae-infected mice. Biochemical analyses for pathogenicity
      achieved with attenuated cercariae showed that while serum aspartate and alanine
      aminotransferases (AST &ALT) were more or less similar, depleted glycogen and
      elevated lipid peroxides were normalized when compared to those infected with
      normal cercariae.

PMID- 14708854
TI  - Human zoonotic cutaneous leishmaniasis and associated sand flies (Diptera:
      Psychodidae) in Sheikh Atiya village, southern Sinai, Egypt.
AB  - Zoonotic cutaneous leishmaniasis is endemic in Sinai Peninsula. Human cases were
      recorded from the northern Sinai, however little was known about the disease in
      southern Sinai. During entomological surveys conducted southern Sinai in summers
      of 1997-1999, a clinically confirmed ZCL case was encountered for the first time
      in Sheikh Atiya village in June 1999. The parasite was isolated and identified as
      L. major using cellulose acetate electrophoresis. A total of 784 phlebotomine
      sand flies were collected. Sand fly species composition at Sheikh Atiya village
      showed that P. papatasi and P. alexandri were the most abundant species in the
      area and each comprises about 47 % of the flies collected. P. sergenti and P.
      kazeruni occurred in very low numbers. All the female flies dissected (N = 304)
      were negative for any Leishmania-like flagellates. When the identified isolate
      was inoculated in the footpads of a clean laboratory colonized Acomys cahirinus
      dimidiatus, a lesion was developed on the site of inoculation 9 months post
      injection. The role of P. alexandri and A. c. dimidiatus in transmission of
      leishmaniasis in southern Sinai remains questionable. Environmental factors
      contributed to the appearance of ZCL in the area are discussed.

PMID- 14708855
TI  - Biomphalaria alexandrina: cellular responses of susceptible and resistant snails
      to Schistosoma mansoni infection.
AB  - Distribution pattern of Schistosoma mansoni miracidia level of host
      susceptility/resistance and the basic cellular responses brought into play during
      the parasite development. Several snail stocks showed a wide spectrum of host
      reaction to the parasite. From the present study, a vigorous "resistant-type"
      cellular response to invading miracidia is seen in the histological sections of
      non-susceptible snails. In this respect, they were classified in our study as
      "resistant snails". B. alexandrina experimentally infected with S. mansoni
      exhibit a wide range of histopathological and immunological changes. The rate of
      phagocytosis as well as the actual number of hemocytes were determined in
      different groups of snails during the infection cycle. The significant
      fluctuation (increase and/or decrease) in circulating hemocyte number was only
      correlated with a shift in hemocyte populations in the first two days after
      exposure to the infective stage. The in vitro phagocytic activity of resistant
      snail hemocytes was found to be higher than that observed in susceptible snails.
      The observed phagocytic activity indicates that susceptible snail hemocytes were
      capable of recognizing parasite antigen in vitro, despite of that, they were not
      able to clear the infection in vivo. Thus suggesting the presence of endogenous
      factors preventing the immune system of susceptible snails from destroying the
      developed parasite larvae. Therefore, the mechanism underlying the susceptibility
      of the snails should be investigated by studying the host-parasite interactions.

PMID- 14708856
TI  - Malaria status in Al-Hodeidah Governorate, Republic of Yemen. Part II: Human
      factors causing the persistence of chloroquine resistant P. falciparum local
      strain.
AB  - Two hundred and nine Yemeni with P. falciparum local strain satisfing all
      criteria of WHO for monitoring chloroquine sensitivity by in vivo and in vitro
      tests in urban and rural population of Al-Hodiedah G. were interviewed to study
      the human factors causing the persistence of chloroquine resistant. A pre
      designed questionnaire sheet was used for every case, which included data
      concerning assessment of chloroquine resistant problem. The results revealed
      that, 54.7% of the studied group had used chloroquine for malaria treatment.
      About 75.0% were used antimalarial drugs by over the counter (OTC) i.e. self
      medication which was more common in rural (76.9%) than urban areas (63.6%).
      Chloroquine resistant was increased with the decrease of education level;
      decrease income/capita/month; among younger age-group (<15 years); and sleeping
      in open air in courts (56.3%, 57.8%, 56.6% and 66.7% respectively). The highest
      percentage of chloroquine resistant (71.0%) was recorded among cases with high
      parasite density (>1000 asexual parasite/microL); in presence of gametocytes
      (82.6%); among cases who did not complete antimalarial course (89.7%); those who
      gave a history of receiving antimalarial drugs without laboratory diagnosis
      (75.0%); those keeping leftover drugs after usage (63.8%) and reading expiry date
      and pamphlet of malaria drugs (26.9%). The results suggested the need for
      increasing of public awareness on emergence and spread of chloroquine-resistant
      and to outline potential risk factors useful for health workers in Yemen,
      especially in remote areas to identify high risk P. falciparum patients for
      chloroquine resistance before treatment.

PMID- 14708857
TI  - A possible role for an enkephalinergic system in the internal defense mechanism
      of Biomphalaria alexandrina exposed to Schistosoma mansoni.
AB  - The present study documents that in Bioniphalaria alexandrina coordinated
      responses to Schistosoma mansoni infection are modulated by receptor-mediated
      opioid signals. Rather comprehensive tests in susceptible and resistant snails
      have demonstrated: I- the presence of an endogenaus opioids in the snail
      hemolymph (in particular, Leu-enkephalin-like material). II- in vitro treatment
      of snail hemocytes with synthetic Leu-enkephalin analogue (DADLE) resulted in the
      modulation of cellular adherence, and phagocytic activity. III- the addition of
      Naloxone, either alone or in combination whith DADLE, generally reduced hemocyte
      activity indicating opioid-receptor-mediated mechanism. V- the presence of DADLE
      or Naloxone modulated the level of IL-2-, TNF-gamma- and FNF-alpha-like molecules
      in S. mansoni resistant and susceptible snails. Specifically, DADLE and DADLE in
      combination with Naloxone generally were found to be capable of modulating
      resistant snail hemocytes at concentrations of 10(-6) and 10(-8) M. Similar
      actions after incubation with the same concentrations were not detected in the
      susceptible snails. These observations demonstrate the existence of a complete
      opioid system in B. alexandrina, associated with susceptibility and resistance to
      S. mansoni infection, the results suggest the role of such opioid system in
      molecular signaling within the host and in host-parasite interactions.

PMID- 14708858
TI  - Vaccination against congenital toxoplasmosis.
AB  - Different types of Toxoplasma gondii vaccines were evaluated using
      parasitological and histopathological means to induce immunity in Swiss pregnant
      mice and their pups against the challenge with virulent RH strain. Immunization
      was performed before mating by using live cyst vaccines (LCV), LCV-IL-2
      combination, irradiated cyst vaccine (ICV) and ICV-IL-2 combination. It was
      demonstrated that pre-immunization with the current vaccines offered significant
      protection of both dams and pups. The highest level of protection was noticed in
      mice which received LCV-IL-2, followed by ICV-IL-2, then LCV and the least
      protection was elicited in dams immunized with ICV alone. The results threw light
      on the possibility of applying such vaccines not only in mice but also in other
      mammalian hosts including human.

PMID- 14708860
TI  - Cellular immune response in giardiasis.
AB  - There was statistically significant difference between all groups of giardiasis
      patients regarding the grade of CD4 lymphocyte infiltration (P<0.001), being more
      marked in symptomatic group. The prevalence of flatulence, anorexia and vomiting
      were more frequent in patients with heavy CD4 lymphocyte infiltration in
      duodenum. A high statistical significant increase was in the mean OD values of
      anti-Giardia duodenal secretory IgA in patients with marked CD4 infiltration in
      duodenum. But, a statistical insignificant difference in mean OD values of anti
      Giardia total serum Ig in patients with different grades of CD4 infiltration in
      symptomatic group. There was statistically significant increased in the mean OD
      values of anti-Giardia total serum Ig in patients with marked intraepithelial CD8
      lymphocyte Infiltration in the duodenum In the asymptomatic group, there was
      statistically insignificant difference in the mean OD values of anti-Giardia
      total serum Ig in patients with different grade of intra-epithelial CD8
      infiltration in symptomatic group. There is statistically significant increased
      in the mean OD values of anti-Giardia total serum Ig in patients with marked
      intra-epithelial CD8 lymphocyte infiltration in the duodenum regarding
      immunohistochemical staining of Giardia antigen in duodenal biopsies. All the 61
      symptomatic giardiasis patients revealed Giardia antigen stains in their duodenal
      biopsies with a sensitivity of 100% while asymptomatic group a sensitivity of
      93.181%. None in the controls showed positive Giardia antigen in the duodenal
      biopsies with 100% specificity.

PMID- 14708859
TI  - The histo-pathology of human giardiasis.
AB  - In giardiasis symptomatic group (I) the prevalence of diarrhoea was 5/7 (71.43%),
      13/13 (100%) in Grade 0, I, II, III and IV pathology respectively which is
      statistically insignificant in comparison to each other (P > 0.05). The
      prevalence of abdominal pain is 71.43%, 73.33%, 95%, 91.67% and 100% in Grade 0,
      I, II, I & IV pathology respectively which is statistically insignificant to each
      other (P > 0.05). The prevalence of flatulence is 42.86%, 40%, 80%, 83.33% and
      100% in Grade 0, I, II, III & IV pathology respectively, was statistically
      significant in comparison to each other (P < or = 0.05) So, the prevalence of
      flatulence is more frequent in patients with marked pathological changes in the
      duodenum. The prevalence of anorexia was 14.29%, 53.33%, 65%, 50% & 100% in Grade
      0, I, II, III & IV pathology respectively, statistically significant in
      comparison to each other (P < or = 0.05). The prevalence of vomiting was 0%,
      13.33%, 15%, 16.67 & 85.71% in Grade 0, I, II, III and IV pathology respectively,
      significant increased in Grade IV and absent in Grade 0 (P < or = 0.001).

PMID- 14708861
TI  - Evaluation of a new enzyme immunoassay for the detection of Helicobacter pylori
      in stool specimens.
AB  - H. pylori infects the gastric mucosa and causes many digestive disorders such as
      peptic ulcer, chronic gastritis and gastric cancer. H. pylori infection relates
      neither to functional health status, nor to intensity of dyspepsia. There is
      evidence that in most patients with H. pylori positive functional dyspepsia do
      not improve with eradication of the organism.This study evaluated the diagnostic
      accuracy of HpSA by determining the sensitivity and specificity of the stool
      antigen test in predicting successful eradication during and after anti microbial
      therapy. The work was conducted on patients who underwent upper gastrointestinal
      endoscopy at Al-Azhar University hospitals. Fifty patients (34 male & 16 female)
      with dyspepsia were selected, the exclusion criteria included use of antibiotics
      and proton pump inhibitors up to one month before the study. All cases were
      submitted to, full history, general and local examination and upper
      gastrointestinal endoscopy. Biopsies were taken from the antrum and body of the
      stomach for rapid urease test and histopathology. Stool samples were taken to
      detect H. pylori stool antigen. Positive patients received eradication treatment
      for one month and H. pylori status was re-determined by rapid urease test,
      histological examination and HpSA test one month later. H. pylori was detected by
      rapid urease test in 29 (58%) dyspeptic patient by histology in 26(52%) dyspeptic
      patient, while H. pylori was detected by HpSA immunoassay in 16 (32%) dyspeptic
      patient. The sensitivity and specificity of HpSA were 57.7% and 95.8%
      respectively. After successful eradication of H. pylori, reassessment by rapid
      urease test and histology revealed curative rate of 86.2% and 84.6% respectively,
      while HpSA immunoassay revealed curative rate 75%. Based on these results, the
      HpSA immunoassay gave sensitivity (75%) and specificity (100%). The H. pylori
      stool test represents an accurate and novel non-invasive concept for diagnosis of
      infection and can be used for daily routine in clinical practice. HpSA is a
      promising non-invasive test for diagnosis of H. pylori infection but may be
      hampered by low patient acceptability. So, HpSA is a valuable test in the pre-and
      post eradication assessment of infection. HpSA can be profitably employed in the
      primary diagnosis of H. pylori infection. This non invasive test could be very
      useful in investigating dyspeptic young patients. Also, it could be used
      profitably in epidemiological studies to determine the prevalence of H. pylori
      infection in the asymptomatic subjects in different communities.

PMID- 14708862
TI  - Efficacy of Mirazid (Commiphora molmol) against fascioliasis in Egyptian sheep.
AB  - The efficacy of Mirazid (Commiphora molmol or Myrrh) was evaluated in sheep
      naturally infected with fascioliasis. Total doses of one or two capsules (300 mg
      each) were given for one, two or three successive days on an empty stomach an
      hour before breakfast. A total dose of 600 mg gave a cure rate of 83.3%, while a
      total dose of 900 to 1200 mg gave a complete cure rate (100%), with no clinical
      side effect. The cure rate was achieved by stool examination and/or
      macroscopically on slaughtering the sheep. Mirazid proved to be safe and very
      effective in sheep fascioliasis in Gharbia Governorate.

PMID- 14708863
TI  - Cellular and humoral immune responses to recombinant Smp17.7 Schistosoma mansoni
      antigen.
AB  - To determine the immunological responses to S. mansoni antigen rSmp17.7, a total
      of 184 subjects, 174 patients from a schistosomiasis endemic area, and 10
      controls were used. Proliferation, cytokine profile in culture supernatants from
      antigen-stimulated peripheral blood mononuclear cells and specific IgG1, IgG3,
      IgG4, IgA, IgM & IgE levels were assessed. The highest stimulation index to
      rSmp17.7 was detected in S. mansoni patients. The evaluation of the cytokine
      profile [IL-2, IL-4 & IFN-gamma] in response to this antigen showed a significant
      increase as demonstrated by ELISA. Specifically, IFN-gamma and IL-2 were
      significantly detected by flow cytometry. IgG1 and IgM were the only Igs which
      showed a significant increase. These results highlight the importance of rSmp17.7
      as a candidate vaccine for schistosomiasis. The results pave the way to
      understand the mechanism of schistosome-vaccine efficacy.

PMID- 14708864
TI  - Molluscicidal and in-vitro schistosomicidal activities of the latex and some
      extracts of some plants belonging to Euphorbiacea.
AB  - Plant molluscicicdes proved to be good means for controlling fresh water snails
      of schistosomiasis. The molluscicidal activities of the natural and lyophilized
      latex extracts of Euphorbia royleana and E. mouritanica and acetonitril and
      chloroform extracts of Jatropha carcus were investigated against Biomphalaria
      alexandrina the intermediate hosts for S. mansoni. The lyophilized latex extract
      of E. royleana showed the highest toxicity against snails with LC90 value of 11
      ppm. While the natural latex extract of E. mouritanica showed the lowest toxicity
      against snails with LC90 value of 60 ppm. While, the acetonitril extract of
      Jatropha carcus gave high toxicity against snails with LC90 value of 6 ppm and
      the chloroform extract gave low toxicity against snails with LC90 value of 55
      ppm. The in-vitro schistosomicidal activities of the lyophilized latex extract of
      E. royleana and the acetonitril extract of J. carcus were studied against S.
      mansoni adults showed that the lyophilized latex extract of E. royleana gave 100%
      mortality after exposure to 30 ppm for 4 consecutive days and 66.7% mortality
      after exposure to 10 ppm for 5 consecutive days. The acetonitril extract of J.
      carcus gave 91.7% mortality after exposure to 100 ppm for 4 consecutive days and
      58.3% mortality after exposure to 50 ppm for 5 consecutive days.

PMID- 14708865
TI  - Mutation in rugose gene locus affects the pigment cell number and alters the
      optic lobe phenotype in the Drosophila visual system.
AB  - In the Drosophila melanogaster, developmental signals orchestrate cell
      differentiation in a sequential manner which lead to precise neural and cellular
      patterns. The previous work demonstrated that the rugose (rg) gene is required
      for proper differentiation of the cone and pigment cells in the Drosophila
      compound eye. In this study, the pigment cell number in several ommatidia in
      rugose mutant eyes was analyzed and showed multiplication of secondary pigment
      cells in the null mutation. In addition, rugose mutant-flies exhibit optic lobe
      defects. The lamina, medulla, lobula and lobula plate are affected by mutation.
      The results suggest that rugose gene encodes a secondary pigment cell specific
      function, and plays an essential role in determining the optic lobe's structure.

PMID- 14708866
TI  - Opportunistic intestinal parasites among children with chronic liver disease.
AB  - Two hundred children were included in this study, 80 patients showing clinical
      and/or biochemical evidence of chronic liver disease, 80 immuno-compromised
      children due to causes other than chronic liver disease and 40 healthy control.
      All were subjected to detailed history, thorough clinical examination,
      investigated by liver function tests and stool examination by special techniques
      for opportunistic intestinal parasites. Autoimmune chronic hepatitis represented
      12.5% of cases with chronic liver disease, hepatic schistosomiasis 30%,
      congenital cholestasis 25%, chronic viral hepatitis 20% and metabolic liver
      diseases 12.5%. The incidence of opportunistic intestinal parasites with chronic
      liver disease (92.5%) was nearly similar to the immuno-compromised ones (90%) and
      significantly higher than controls (30%). Mixed infection was not detected in
      controls while 57.5% of patients with chronic liver disease and 35% of immuno
      compromised were infected by 2 parasites and 12.5% of each group was infected by
      more parasites. The commonest parasites were G. lamblia, E. histolytica and C.
      parvum but no Strongyloides stercoralis was detected. Children with chronic liver
      disease can be considered immuno-compromised and are liable to infection by
      opportunistic intestinal parasites.

PMID- 14708867
TI  - Methods used in the diagnosis of malaria: where do we stand?
AB  - In developing nations, limited resources lead to inadequate malaria diagnosis. In
      wealthy countries, poor familiarity with malaria may lead to clinical and
      laboratory misdiagnosis. Giemsa thick and thin blood films remain the current
      standard for diagnosis. Although it has good sensitivity and allows species
      identification and parasite counts, it is time consuming, requires microscopic
      expertise and maintenance of equipment. Microscopy with fluorescent stains (QBC),
      dipstick antigen detection of HRP2 and pLDH (Parasight-F, ICT Malaria Pf,
      OptiMAL), polymerase chain reaction assays and some automated blood cell
      analyzers offer new approaches and are reviewed here, with emphasis on clinical
      relevance and the potential to complement conventional microscopy.

PMID- 14708868
TI  - Human pathogenic protozoa in bivalves collected from local markets in Alexandria.
AB  - Bivalves are filter feeders concentrating pathogens from waters and are often
      eaten raw. Two species, Caelatura Iaronia pruneri and Donax trunculus limiacus
      commonly known as Gandofli and Om el Kholool respectively were examined.
      Shellfish were collected from markets in Alexandria to detect any human
      pathogenic protozoa in them. The infectivity of the detected protozoa was studied
      by experimental animal inoculation. The results revealed the presence of
      infectious Cryptosporidia oocysts and Microsporidia spores in both bivalves.
      Cyclospora sp. was detected only in Gandofli but was non-infectious to mice.
      There is a potential risk of acquiring protozoa infections if shellfish are eaten
      raw or insufficiently cooked.

PMID- 14708869
TI  - In vitro effect of Mirazid on Schistosoma mansoni worms.
AB  - Measuring Mirazid ability for contracting the worm muscle and its effect on the
      worm surface ultra-structure can be used to monitor the in vitro effect of any
      drug. This study aims at investigating the actual effect of Mirazid (a new
      schistosomicide; purified oleo-resin extract of Myrrh, derived from Commiphora
      molmol plant) on S. mansoni worms by detecting its in vitro effect. Three groups
      of white albino mice (5 mice in each group) were infected by 100 cercariae for
      each mouse. The 3rd group served as a control group. Seven weeks post-infection
      the mice were sacrificed, perfused and worms were collected. Muscle tension of
      the worms collected from the first group of mice, was assayed in response to
      Mirazid in rising concentrations of 100, 200, 300 and 400 nM. The in vitro effect
      of Mirazid on the muscle tension of single S. mansoni worm was determined using a
      special device to determine percentage of change in worm length (% shortening).
      The drug elicited somatic muscle contraction and reached the highest response
      with 400 nM Mirazid. The maximal increase in the muscle tension (48% shortening)
      was induced by the highest concentration (400 nM) of the drug. The worms
      collected from the second group of mice were scanned by electron microscopy. The
      worms were exposed each to 10 ul of Mirazid in concentration of 10(-6) and
      collected after 10, 20 and 30 minutes of exposure. Ten minutes exposure caused
      disruption of the tegument and collapse of tubercles. After 20 minutes, the
      tegument appeared edematous with more disruption and more shrinkage of tubercles.
      After 30 minutes, the tegument appeared markedly edematous with extensive
      disruption of the inter-papillary areas and sensory bulbs. The spines covering
      the tubercles appeared to be lost.

PMID- 14708870
TI  - Microcirculatory dysfunction during intestinal ischemia-reperfusion.
AB  - Oxido-reductive stress is a crucial factor of the tissue response during ischemia
      reoxygenation injuries. Reperfusion affects primarily the microvasculature in a
      manner consistent with an acute inflammatory reaction. In this respect, the
      salient data suggest an important connection between endothelial cell-derived
      humoral mediators and the perivascular mast cell system. Increased endothelin-1
      and decreased nitric oxide formation, mast cell degranulation and leukocyte
      accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too.
      Constitutively produced nitric oxide inhibits, while increasingly formed
      endothelin-1 significantly enhances the degranulation of the intestinal mast
      cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a
      secondary role in reperfusion-induced structural injury, but contributes
      significantly to leukocyte recruitment into the reperfused intestinal mucosa. It
      is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is
      involved in the mechanism of ischemia-reperfusion-induced endothelial cell
      leukocyte interactions, where mast cells act to amplify the process of leukocyte
      sequestration. The alteration in the balance between endothelial cell-derived
      proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a
      significant influence on the mucosal integrity, and the antagonism of endothelin
      A receptor activation in this setting tips the equilibrium toward tissue salvage.

PMID- 14708871
TI  - Pathophysiology and functional consequences of human partial epilepsy: lessons
      from positron emission tomography studies.
AB  - Positron emission tomography (PET) is a powerful clinical and research tool that,
      in the past two decades, has provided a great amount of novel data on the
      pathophysiology and functional consequences of human epilepsy. PET studies
      revealed cortical and subcortical brain dysfunction of a widespread brain
      circuitry, providing an unprecedented insight in the complex functional
      abnormalities of the epileptic brain. Correlation of metabolic and neuroreceptor
      PET abnormalities with electroclinical variables helped identify parts of this
      circuitry, some of which are directly related to primary epileptogenesis, while
      others, adjacent to or remote from the primary epileptic focus, may be secondary
      to longstanding epilepsy. PET studies have also provided detailed data on the
      functional anatomy of cognitive and behavioral abnormalities associated with
      epilepsy. PET, along with other neuroimaging modalities, can measure longitudinal
      changes in brain function attributed to chronic seizures as well as therapeutic
      interventions. This review demonstrates how development of more specific PET
      tracers and application of multimodality imaging by combining structural and
      functional neuroimaging with electrophysiological data can further improve our
      understanding of human partial epilepsy, and helps more effective application of
      PET in presurgical evaluation of patients with intractable seizures.

PMID- 14708872
TI  - Extents of visual, auditory and bimodal receptive fields of single neurons in the
      feline visual associative cortex.
AB  - Extracellular microelectrode recordings were carried out on 150 neurons in the
      anterior ectosylvian sulcal region of halothane-anesthetized, immobilized,
      artificially ventilated cats. Fifty-nine neurons were visual, 60 were auditory
      and 31 were bimodal visual-auditory. As the extent of the receptive fields has
      never been exactly determined, we introduced a quasi-objective, computer-based,
      statistical method in order to estimate the receptive field sizes in the anterior
      half of the perimeter. The visual, auditory and bimodal cells had very large
      receptive fields, often with portions extending well into the ipsilateral
      hemifield. The mean extents of the visual and auditory receptive fields in the
      horizontal plane were 75.75 degrees (N=59, SD: +/- 28.620, range: 15-135
      degrees), and 132.5 degrees (N=60, SD: +/- 46.72 degrees, range: 15-165 degrees)
      respectively. These data suggest that a single visual neuron can carry
      information from the whole visual field of the right eye and a single auditory
      unit can carry information of azimuths throughout the whole area of the
      horizontal plane studied. The mean extent of the bimodal receptive fields in the
      horizontal plane was 82.1 degrees (N=31, SD: +/- 24.24 degrees, range: 30-135
      degrees). In 21 of the 31 bimodal cells we observed a facilitatory interaction
      between visual and auditory stimuli. The mean extent of the facilitatory
      interactions in these cells was 75.75 degrees (N=21, SD: +/- 24.56 degrees,
      range: 45-135 degrees).

PMID- 14708873
TI  - Reduction of the prenatal hypoxic-ischemic brain edema with noscapine.
AB  - Cytotoxic free radicals and release of several neurotransmitters such as
      bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We
      have studied the efficacy of noscapine, an opium alkaloid and a bradykinin
      antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d
      old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was
      produced by legation of the right common carotid artery followed by 3 h of
      hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received
      noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post
      recovery for the assessment of cerebral damage by histological methods. Our
      results showed that noscapine was an effective agent in reducing the extent of
      brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is
      concluded that noscapine may be a useful drug in the managements of patients
      after stroke.

PMID- 14708874
TI  - Total monoamine oxidase activity in the hypothalamus, ovary and uterus of rats
      with an extreme number of ovarian corpora lutea.
AB  - The activity of total monoamine oxidase (MAO) in the rat ovary and uterus
      fluctuates significantly under various physiological conditions. We analyzed
      total MAO activity in the hypothalamus, uterus and ovary in adult rats, having an
      extreme number of corpora lutea (hyperluteinized ovaries) resulting from the
      mechanical lesions in the posterior hypothalamic region of neonatal rats. Total
      MAO activity in the hypothalamus (30.21 +/- 1.53 pmol/mg tissue/min) and uterus
      (3.16 +/- 0.61 pmol/mg tissue/min) of rats with hyperluteinized ovaries did not
      show a significant difference as compared to that of intact controls (31.09 +/-
      1.72 and 2.90 +/- 0.40 pmol/mg tissue/min, respectively). In contrast, in the
      ovaries of hyperluteinized rats, total MAO activity (21.16 +/- 1.70 pmol/mg
      tissue/min) was significantly higher (p<0.01) when compared to that of intact
      controls (13.61 +/- 1.30 pmol/mg tissue/min). The increased MAO activity in the
      hyperluteinized ovaries may be attributed to the increased number of transformed
      and accumulated corpora lutes as a consequence of diminished luteolysis.

PMID- 14708875
TI  - The effect of the pulsatile electromagnetic field in children suffering from
      bronchial asthma.
AB  - From the bibliography it is well known that pulsatile electromagnetic field has
      an anti-inflammatory and analgesic effect. It causes vasodilatation,
      myorelaxation, hyper-production of connective tissue and activation of the cell
      membrane. Therefore our aim was to study the possible therapeutic effect of
      pulsatile electromagnetic field in asthmatic children. Forty-two children
      participating in this study were divided in two groups. The 1st group consisting
      of 21 children (11 females, 10 males, aged 11.8 +/- 0.4 yr) was treated by
      pulsatile electromagnetic field and pharmacologically. The 2nd group served as
      control, consisting also of 21 children (11 females, 10 males, aged 11.7 +/- 0.3
      yr) and was treated only pharmacologically. Therapeutic effect of the pulsatile
      electromagnetic field was assessed on the basis of pulmonary tests performed by
      means of a Spirometer 100 Handi (Germany). The indexes FVC, IVC, ERV, IRV, FEV1,
      FEV1/FVC%, MEF75,50,25, PEF, PIF and the changes of the flow-volume loop were
      also registered. The pulsatile electromagnetic field was applied by means of the
      device MTU 500H, Therapy System (Brno, Czech Republic) for 5 days, two times
      daily for 30 minutes (magnetic induction: 3 mT, frequency: 4 Hz as recommended by
      the manufacturer). The results in children of the 1st group showed an improvement
      of FVC of about 70 ml, IVC of about 110 ml, FEV1 of about 80 ml, MEF75 of about
      30 ml, PEF of about 480 ml, PIF of about 550 ml. The increases of ERV, IRV and
      FEV1/FVC and decreases of MEF25,50 were statistically insignificant. The results
      in the 2nd group were less clear. The flow-volume loop showed a mild improvement
      in 14 children. This improvement in the 2nd group was less significant. The
      clinical status of children and their mood became better. We believe that the
      pulsatile electro-magnetotherapy in children suffering from asthma is effective.
      On the basis of our results we can recommend it as a complementary therapy.

PMID- 14708876
TI  - Both zinc deficiency and supplementation affect plasma melatonin levels in rats.
AB  - At physiological levels, zinc and various hormones affect each other
      reciprocally. Reduction in zinc levels in pinealectomized rats suggests the
      relation between zinc and melatonin. The effect of both zinc deficiency and
      supplementation on plasma melatonin levels in rats were investigated in this
      study. The study was done in Selcuk University, Experimental Medicine Research
      and Application Center. Twenty-four adult male Sprague Dawley rats were divided
      into 3 groups. Eight rats were fed with zinc-deficient diet. Zinc supplementation
      was administered intaperitoneally to 8 rats. The remaining 8 rats were used as
      controls. All rats sacrificed 3 weeks later. Plasma melatonin and zinc levels
      were determined. The plasma zinc levels of the zinc-supplemented group were
      higher than those of the other groups as expected (P<0.01). Similarly, the
      melatonin levels in the zinc-supplemented group were higher than those in the
      other groups. A significant decrease was observed in melatonin levels of the zinc
      deficient group compared to the control and zinc-supplemented group (P<0.01). The
      results of this study suggest that zinc deficiency decreases the melatonin levels
      and zinc supplementation may increase the plasma melatonin levels in rats.

PMID- 14708877
TI  - Mass spectrometry in laboratory medicine.

PMID- 14708878
TI  - Mass spectrometry-based proteomics: current status and potential use in clinical
      chemistry.
AB  - For some years now, scientists have been spending a lot of effort in developing
      methods to analyse and compare complex protein samples. One of the goals of such
      global analyses of what is known as proteomes is to discover specific protein
      markers--or fingerprints of protein markers--from various types of affected
      biological samples. Considering the battery of technologies currently available,
      mass spectrometry (MS) constitutes an essential tool in proteomics. We describe
      here the type of MS instrumentation that is currently dedicated to proteomics
      research. We also describe the major experimental workflows that are typically
      used in proteomics today, with a focus on those incorporating MS as a major
      analysis tool.

PMID- 14708879
TI  - Application of gas chromatography-mass spectrometry for analysis of isoprostanes:
      their role in cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the major cause of death in the Western
      hemisphere. Oxidative stress is involved in the pathophysiology of cancer,
      neurodegenerative conditions and CVD. Lipid peroxidation is one of the oxidative
      modifications possible in biological systems. The isoprostanes are derivatives of
      one specific lipid, i.e., arachidonic acid, after lipid peroxidation. Several
      isoprostanes have been identified in biological tissues and fluids, among them 8
      iso prostaglandin F2alpha (8-iso-PGF2alpha, 8-epi-PGF2alpha, iPF2alpha-III, 15
      F2t-IsoP) and its metabolite, 2,3-dinor-4,5-dihydro-8-iso-PGF2alpha. The
      isoprostanes are reliable in vivo markers of lipid peroxidation in humans: they
      are endogenously formed, characteristic in structure, ubiquitous in nature,
      stable in- and ex vivo and reliably quantitatable. In this Review, different
      analytical approaches will be discussed including immunologic, chromatographic
      and spectrometric techniques with the main emphasis on mass spectrometry.
      Analysis of isoprostanes applying radio immunoassay (RIA), enzyme immunoassay
      (EIA), high performance-liquid chromatography (HPLC), liquid chromatography
      tandem mass spectrometry (LC-tandem MS), gas chromatography-mass spectrometry (GC
      MS) and GC-tandem MS will be exemplified in the field of cardiovascular research.
      Results from several clinical studies are included indicating the validity of
      isoprostanes as surrogate parameters of oxidative stress in cardiovascular
      disease.

PMID- 14708880
TI  - The application of clinical proteomics to cancer and other diseases.
AB  - The term "clinical proteomics" refers to the application of available proteomics
      technologies to current areas of clinical investigation. The ability to
      simultaneously and comprehensively examine changes in large numbers of proteins
      in the context of disease or other changes in physiological conditions holds
      great promise as a tool to unlock the solutions to difficult clinical research
      questions. Proteomics is a rapidly growing field that combines high throughput
      analytical methodologies such as two-dimensional gel electrophoresis and SELDI
      mass spectrometry methods with complex bioinformatics to study systems biology-
      the system of interest is defined by the investigator. Even with all its
      potential, however, studies must be carefully designed in order to differentiate
      true clinical differences in protein expression from differences originating from
      variation in sample collection, variation in experimental condition, and normal
      biological variability. Proteomic analyses are already widely in use for clinical
      studies ranging from cancer to other diseases such as cardiovascular disease,
      organ transplant, and pharmacodynamic studies.

PMID- 14708881
TI  - Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in
      serum with liquid chromatography-electrospray ionization mass spectrometry.
AB  - Therapeutic drug monitoring of antipsychotic drugs has become more and more
      important in recent years, and a well-organized therapeutic drug monitoring
      service with fast turn-around times is very important. Therefore, an analytical
      method coupling high-performance liquid chromatography to mass spectrometry with
      electrospray ionization in the positive mode was established in our laboratory.
      Amitriptyline, citalopram, clomipramine (including norclomipramine), desipramine,
      dibenzepin, doxepin (including nordoxepin), escitalopram, flupentixol,
      fluphenazine, fluvoxamine, imipramine, nortriptyline, opipramol, pipamperone,
      reboxetine, thioridazine, trimipramine and zuclopenthixol were separated on a
      reversed-phase C18 column. The mobile phase consisted of acetonitrile and
      ammonium acetate buffer pH 4. Because of different organic solvents used for the
      liquid-liquid extraction and the different volumes of mobile phases in which the
      residues were dissolved, four analytical systems had to be applied. Within the
      run-time of maximal 10 minutes the 13 antidepressant and five neuroleptic drugs
      were baseline separated on the corresponding mass-to-charge track. The
      calibration range of each drug was linear, all between-day coefficients of
      variation were below 7% and the recovery rates were between 60 and 103%. Using 1
      ml of serum, the lower limits of quantification were between 1.2 and 54 nmol/l
      for the different drugs and below the therapeutic range for each of the different
      drugs.

PMID- 14708882
TI  - Mass spectrometric analysis of human transferrin in different body fluids.
AB  - In this study, we present a versatile new procedure for the analysis of
      transferrin and its isoforms isolated from human body fluids such as serum,
      plasma, and cerebrospinal fluid. This method is based on a three-step procedure:
      (i) isolation of transferrins using anion-exchange chromatography with UV
      detection; (ii) concentration of the transferrin fraction; (iii) detection of the
      transferrins with liquid chromatography-electrospray mass spectrometry. Pre
      analytical sample procedures can be omitted and no immunoaffinity columns or
      transferrin-specific immunoassays were used. Anticoagulants such as heparin,
      EDTA, citrate, and oxalate do not interfere with our analysis. According to their
      respective molecular masses, up to ten different isoforms of transferrin could be
      identified in a serum sample from a patient with a congenital disorder of
      glycosylation type Ia (CDG-Ia). The method was successfully applied to different
      pathological samples from patients with CDG-Ia, CDG-Ib, CDG-Ic, CDG-Ie, CDG-If,
      and CDG-IIa. Additionally, samples from alcohol consumers that were found with
      turbidimetric immunoassay to contain increased levels of carbohydrate-deficient
      transferrin were analyzed.

PMID- 14708883
TI  - Profiling and in vivo quantification of proteins by high resolution mass
      spectrometry: the example of goserelin, an analogue of luteinizing hormone
      releasing hormone.
AB  - Proteins are essential biomolecules which are frequently involved in major
      pathological syndromes and are widely used as diagnostic markers or therapeutic
      agents. The emergence of proteomics will doubtless further increase the
      significance of proteins both in the clinic and in the life sciences in general.
      Our main objective is to offer innovative solutions to what we like to call the
      "post-proteomics era". To achieve our goal, we intend to develop novel approaches
      and technologies for in vivo metabolic studies of proteins using mass
      spectrometry (MS), focusing on pharmacokinetics and pharmacodynamics. Using
      goserelin as a model, we have successfully developed and validated a liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and
      quantification of an intact analogue of luteinizing hormone-releasing hormone
      (LHRH) in small volumes of rat plasma samples at concentrations ranging from 0.3
      to 405.0 microg/l. To this end, a microbore reversed-phase-HPLC system was
      coupled on-line to a tandem high resolution quadrupole time-of-flight (Q-TOF)
      instrument fitted with an electrospray ion source and operated in LC-MS/MS mode.
      External calibration was used and the high resolution was crucial to discard
      contaminating signals, which would not have been possible with the more
      conventional triple quadrupole mass spectrometers operated in a static mode. For
      low sample amounts, calibration curves were constructed corresponding to rat
      plasma levels of 0.3 to 16.4 microg/l and found to be of third order with a
      coefficient of determination greater than 0.999. The relative standard deviation
      was found to be lower than 15%. A lower limit of detection (LLOD) of 0.17
      microg/l and a lower limit of quantification (LLOQ) of 0.3 microg/l were
      determined.

PMID- 14708884
TI  - Determination of nicotine and its major metabolite cotinine in plasma or serum by
      gas chromatography-mass spectrometry using ion-trap detection.
AB  - A specific method has been developed for the quantitative determination of
      nicotine and its major metabolite cotinine in plasma or serum of active and
      passive smokers. Deuterium-labelled nicotine and cotinine were used as internal
      standards. The amounts of nicotine and cotinine present in a sample of plasma or
      serum were extracted with a simple extraction procedure (liquid-liquid or solid
      phase extraction). The extracts were analysed by gas chromatography coupled with
      mass spectrometry using ion-trap detection. The analysis was done in positive
      chemical ionisation with methanol as the liquid reagent. The method has been
      demonstrated to be linear up to 1000 microg/l. Limits of quantification for
      nicotine and cotinine are 10 and 5 microg/l, respectively with liquid-liquid
      extraction, and 1 microg/l for each of the compounds with solid-phase extraction.
      The present method has been applied to several real cases.

PMID- 14708885
TI  - Analysis of nitrofuran metabolites in food by high-performance liquid
      chromatography with tandem mass spectrometry detection.
AB  - A reliable and sensitive procedure is presented for the analysis of nitrofuran
      metabolite residues in foods of animal origin, like poultry and shrimp. The
      method is based on a one-step extraction/derivatization, followed by solid-phase
      extraction clean-up with polymeric phase cartridges. The separations were carried
      out by liquid chromatography coupled with tandem mass spectroscopy detection.
      Results from the full validation of the procedure and from a survey of food
      available from the Swiss market, with the analysis of 236 samples of shrimp,
      poultry, fish and rabbit, are presented and demonstrate that this method is
      satisfactory in order to control nitrofuran residues in foods of animal origin.

PMID- 14708886
TI  - Automated LC-MS method for the fast stereoselective determination of methadone in
      plasma.
AB  - Methadone (MTD) is a chiral drug widely used for the treatment of opioid
      dependence for which a rapid analytical method for the determination of each
      enantiomer would be advantageous. In order to improve method sensitivity and to
      automate the entire analytical process, a column-switching configuration has been
      developed. An online extraction system coupled to a cellulose-based chiral
      stationary phase (CSP), namely Chiralcel OJ-R, was used and detection was
      performed by mass spectrometry. Fifty microl of plasma were injected into the
      liquid chromatography-mass spectrometry (LC-MS) system after addition of
      acetonitrile (ACN) containing methadone deuterated D9 (MTD-D9) (internal
      standard) and centrifugation. For the rapid extraction step, a large particle
      size support was selected. A baseline separation of MTD enantiomers was obtained
      in less than 12 min. Trueness and precision were evaluated with control samples
      at 500 ng/ml of (R,S)-methadone. Trueness values were 106.6% and 103.0% for (R)
      MTD and (S)-MTD, respectively, with a coefficient of variation inferior to 2.5%
      for both compounds. Finally, a good concordance was found using this method for
      analysis of plasma samples from patients in maintenance treatment as compared to
      a previously described HPLC-UV method after liquid-liquid extraction.

PMID- 14708887
TI  - Proteome analysis of diseased joints from mice suffering from collagen-induced
      arthritis.
AB  - Strains of mice that are susceptible to autoimmunity have provided experimental
      models to analyze the molecular basis for the complex multifactorial inheritance
      of human autoimmune disease. In this study proteins associated with collagen
      induced arthritis (CIA) in mice were experimentally identified using a global
      proteomics approach. Two-dimensional gels of proteins from inflamed and non
      inflamed joints showed a distinguished protein profile visualizing about 530
      Coomassie-stained protein spots in the pH 4-7 range. A total of 76 spots were
      identified by peptide mass fingerprinting with good confidence. They included
      proteins of cytoskeletal origin, chaperones, enzymes and also some signal
      transduction molecules. Comparison to gels from non-inflamed paws pointed to
      proteins that were differentially expressed between the control and diseased
      state. Ferritin light chain and antioxidant protein 2 were slightly more
      abundant, lymphoid enhancer binding factor 1 slightly, but significantly, less
      abundant in inflamed paws. Fourteen of the identified proteins were the products
      of genes that had increased transcript levels in the diseased state. However, on
      the protein level no significant differences were found in comparison to the
      controls. This study provides us with the framework for more detailed approaches
      to understanding the complex disease arthritis that go beyond global proteomics.

PMID- 14708888
TI  - Quantitative analysis of bile acids in human plasma by liquid chromatography
      electrospray tandem mass spectrometry: a simple and rapid one-step method.
AB  - Bile acids play a pivotal role in the metabolism of cholesterol and lipids. Their
      blood concentrations are important prognostic and diagnostic indicators of
      hepatobiliary and intestinal dysfunction. This class of molecules comprises a
      heterogeneous group of compounds with a common cholesterol scaffold. Recently,
      the introduction of liquid chromatography coupled to tandem mass spectrometry
      methods has revealed an innovative path in the quantisation of specific bile
      acids in biological specimens. A robust and sensitive method has been developed
      based on high performance liquid chromatography separation coupled to an
      electrospray triple-quadrupole mass spectrometer. Human plasma samples were
      analysed on a C18 reverse-phase column. The elution profiles were monitored in
      multiple reaction-monitoring mode, quantifying and identifying each analyte by
      its own unique precursor to product patterns. A linear correlation over a broad
      range of bile acid concentrations (0.1-100 microM) was observed. The average
      recovery period for all of the analysed bile acids was 98 +/- 3%. Intra-day and
      inter-day precision averages were 2% and 5.4%, respectively. The determination
      was achieved within a single chromatographic run for all unconjugated, glycine-
      and taurine-conjugated isomeric forms of bile acids. As a proof of principle this
      method has been validated on a small subset of cholestatic patients (n = 7) and
      compared to appropriate clinical controls (n = 10). Based upon our encouraging
      experimental results, the described HPLC separation coupled to tandem mass
      spectrometry method for the analysis of bile acids in biological samples is
      deemed a robust and accurate procedure. Consequently, we propose this technique
      as a suitable candidate method for the identification and quantitation of bile
      acids in routine analysis.

PMID- 14708889
TI  - Organic acids in the second morning urine in a healthy Swiss paediatric
      population.
AB  - Organic acid analysis is used for the early detection/ exclusion and for the
      follow-up of inherited disorders of amino acid and organic acid metabolism.
      Urinary organic acid concentrations in 417 healthy Caucasian children (1 day to
      17 years of age) were determined after liquid solid extraction, as their
      trimethylsilyl derivatives, by gas chromatography and mass spectrometry.
      Concentrations of most of the organic acids adjusted for creatinine tend to
      decrease with age. No differences were found between gender except for the Krebs
      cycle intermediates in the older age groups. In neonates, the immaturity of the
      neonatal kidney led to a much larger variation of organic acid levels when
      related to creatinine. The low number of subjects (n = 36-52) per age class
      resulted in large 95% confidence intervals of the percentiles used for decision.
      This must be taken into account when using the data for exclusion or diagnosis of
      disorders.

PMID- 14708890
TI  - Decreasing incidence of hepatocellular carcinoma among children following
      universal hepatitis B immunization.
AB  - Hepatocellular carcinoma (HCC) is one of the 10 most common malignant tumors
      worldwide. Chronic infection with hepatitis B or C virus is closely related to
      hepatocarcinogenesis. The outcome of current therapies for HCC is not
      satisfactory. Prevention is the best way to control HCC. Among the various
      strategies of HCC prevention, immunization against hepatitis B virus infection is
      the most effective. Universal hepatitis B immunization has proved to be effective
      in reducing the incidence of HCC to 1/4-1/3 of that in children born before the
      hepatitis B vaccination era in Taiwan. The problems we face in achieving global
      control of hepatitis-related HCC include: (1) no effective vaccine for the
      prevention of hepatitis C and its related HCC; (2) no immunization program for
      hepatitis B in areas with inadequate resources; (3) poor compliance to the
      immunization program as a result of ignorance, anxiety, or poverty; and (4)
      vaccine failure. Integration of the hepatitis B vaccination program into the
      expanded program of immunization for all infants throughout the world will be
      most urgent and important for HCC control. The reduction of the incidence of HCC
      will be seen in adults 30-40 years of age after the launch of the universal
      hepatitis B vaccination program. This concept of cancer vaccine can be applied to
      other infectious agents and their related cancers.

PMID- 14708891
TI  - Genetic cholestasis, causes and consequences for hepatobiliary transport.
AB  - Bile salts take part in an efficient enterohepatic circulation in which most of
      the secreted bile salts are reclaimed by absorption in the terminal ileum. In the
      liver, the sodium-dependent taurocholate transporter at the basolateral
      (sinusoidal) membrane and the bile salt export pump at the canalicular membrane
      mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular
      secretion is the driving force for the enterohepatic cycling of bile salts and
      most genetic diseases are caused by defects of canalicular secretion. Impairment
      of bile flow leads to adaptive changes in the expression of transporter proteins
      and enzymes of the cytochrome P-450 system involved in the metabolism of
      cholesterol and bile acids. Bile salts act as ligands for transcription factors.
      As such, they stimulate or inhibit the transcription of genes encoding
      transporters and enzymes involved in their own metabolism. Together these changes
      appear to serve mainly a hepatoprotective function. Progressive familial
      intrahepatic cholestasis (PFIC) results from mutations in various genes encoding
      hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or
      permanent cholestasis. The relapsing type of cholestasis is called benign
      recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type
      1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene.
      This is associated with permanent cholestasis since birth. Serum gamma
      glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2.
      Bile diversion procedures, causing a decreased bile salt pool, have a beneficial
      effect in a number of patients with these diseases. However, liver
      transplantation is often necessary. PFIC type 3 is caused by mutations in the
      MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane.
      Because of the inability to secrete phospholipids, patients with PFIC type 3
      produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum
      gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is
      useful for patients with a partial defect. Liver transplantation is a more
      definitive therapy for these patients.

PMID- 14708892
TI  - Local antigen-driven oligoclonal expansion of B cells in the liver portal areas
      of patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: The antigen-driven clonal proliferation of B cells within target
      tissue has been reported in some autoimmune diseases. The purpose of this study
      was to examine the clonal characteristics of B cells in the liver portal area of
      primary biliary cirrhosis (PBC). METHODS: The liver portal area was
      microdissected from liver biopsy sections from two PBC patients. Genomic DNA was
      extracted and rearranged immunoglobulin heavy chain variable region (VH) genes
      were amplified and sequence analyzed. RESULTS: Sixteen VH sequences from portal
      area 1A of patient 1 had three different rearrangements. Nineteen VH sequences
      from portal area 1B of this patient had three different rearrangements. In three
      sequences from the portal area 1B, a stepwise accumulation of somatic mutations
      was observed. Between the sequences from the two portal areas, no common VH
      sequence was observed. In patient 2, 15 VH sequences from portal area 2A had
      three different rearrangements. Fourteen VH sequences from portal area 2B had two
      different rearrangements. One rearrangement was present both in the portal area
      2A and portal area 2B. CONCLUSION: The oligoclonal B cell proliferation and
      stepwise accumulation of somatic mutations suggested that an antigen-driven B
      cell response had occurred in the portal area of PBC.

PMID- 14708893
TI  - Gene expression in HCV-associated hepatocellular carcinoma--upregulation of a
      gene encoding a protein related to the ubiquitin-conjugating enzyme.
AB  - BACKGROUND/AIMS: To investigate gene expression in HCV-associated human
      hepatocellular carcinomas (HCC) by identifying up- and down-regulated genes.
      METHODS: Differential display RT-PCR was used to compare levels of gene
      expression in tumorous and non-tumorous tissues from the same livers.
      Differential expression was confirmed using a ribonuclease protection assay
      (RPA). The relative expression levels of one candidate gene were studied in
      various normal tissues and malignant cell lines using a multiple tissue
      expression (MTE) array. Further characterisation of this gene was carried out
      using nucleotide sequence analysis programmes and Northern hybridisation.
      RESULTS: Fifty-two differentially expressed cDNA fragments were identified and 29
      were cloned, sequenced and compared with the nucleotide sequence database. RPA
      confirmed reproducibly that one particular cDNA was upregulated in the tumour
      cells. Analysis using the MTE array revealed that this selected candidate gene is
      expressed at high levels in various human tumour cell lines. The expression
      levels in HCV-associated HCC were higher than in other tumours. Investigation
      revealed that this novel gene lies on chromosome 17. The transcript is
      approximately 2.5 kb in size and encodes a protein similar to the ubiquitin
      conjugating enzyme. CONCLUSIONS: The ubiquitin system may be involved in HCV
      related hepatocarcinogenesis and in the development of other cancers.

PMID- 14708894
TI  - Expression of 8-hydroxy-2'-deoxyguanosine in chronic liver disease and
      hepatocellular carcinoma.
AB  - Reactive oxygen species may be involved in the progression of chronic liver
      disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether
      clinicopathological findings in liver diseases are related to oxidative DNA
      damage, hepatic expression of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) was
      examined in 75 liver disease patients, which included 32 chronic hepatitis (CH),
      13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8-OHdG
      positive hepatocytes than LC (P < 0.05). In CH and LC, the number of 8-OHdG
      positive hepatocytes was correlated with alanine aminotransferase and asparate
      aminotransferase (P < 0.01 and P < 0.05, respectively). Of 30 HCC cases, 25 cases
      (83%) showed stronger immunoreactivity than non-cancerous counterparts. The
      patients with poorly differentiated HCC had a larger tumor size and higher levels
      of AFP, and exhibited higher labeling indices of PCNA-, TUNEL- and 8-OHdG
      positive cells than those with well and moderately differentiated HCC. Our
      findings suggest that oxidative DNA damage is increased in association with
      necroinflammation in chronic liver disease and determination of 8-OHdG is useful
      in assessing high-grade malignancy in HCC.

PMID- 14708895
TI  - Isolated tuberculous liver abscesses with multiple hyperechoic masses on
      ultrasound: a case report and review of the literature.
AB  - Cases of isolated tuberculous liver abscess are rare. The diagnosis is often
      delayed or missed because of nonspecific symptoms and the disease's rare
      occurrence. Less than 25 cases have been documented in the imaging literature to
      date. This report demonstrates the difficulty in correctly diagnosing local
      hepatic tuberculosis. We report the case of a 56-year-old male with hepatitis C
      related liver cirrhosis and end-stage renal disease treated with hemodialysis,
      who developed intermittent fever and hepatomegaly with unusual multiple
      hyperechoic hepatic lesions on ultrasound. To our knowledge, this is only the
      second reported case of hyperechoic mass-like hepatic lesions on ultrasound and
      the only case without pulmonary involvement. A greater awareness of this rare
      clinical entity may prevent needless surgical interventions, because the
      prognosis of hepatic tuberculous abscess is good for the majority of patients if
      diagnosed early and prompt, effective treatment is administered.

PMID- 14708896
TI  - Ornidazole-induced liver damage: report of three cases and review of the
      literature.
AB  - Metronidazole and ornidazole, synthetic nitroimidazole derivatives, are used in
      the treatment of infections caused by anaerobic bacteria and protozoa. The drugs
      are well tolerated and serious side effects are very rarely encountered.
      Hepatotoxicity is a rare side effect and hitherto only six cases have been
      reported. We describe three patients who developed hepatitis after ornidazole use
      and review the previously reported cases. All three cases used ornidazole in
      conventional doses and developed hepatitis and associated cholestasis. They
      improved 1-2 months after discontinuation. We concluded that nitroimidazole
      derivatives may cause hepatotoxic damage resembling acute cholestatic hepatitis.
      Early recognition and withdrawal of the drug may prevent further damage.

PMID- 14708897
TI  - Epitope mapping on E1alpha subunit of pyruvate dehydrogenase complex with
      autoantibodies of patients with primary biliary cirrhosis.
AB  - BACKGROUND: A major mitochondrial autoantigen recognized by sera of patients with
      primary biliary cirrhosis (PBC) is dihydrolipoamide acetyltransferase (E2) of the
      pyruvate dehydrogenase complex (PDH). The alpha subunit of pyruvate decarboxylase
      (E1alpha) of PDH is also recognized in some E2-reactive PBC sera, suggesting that
      the occurrence of autoimmunity against Elalpha is subsequent to that against E2.
      METHODS. To investigate the mechanism inducing autoimmunity against E1alpha, we
      surveyed immunoreactive sequences of E1alpha by ELISA with synthesized
      oligopeptides, and determined minimum amino acid residues for each determinant.
      RESULTS: The major determinants of E1alpha appeared to reside in its N-terminal
      region, apparently forming 'nested epitopes', and all E1alpha-reactive PBC sera
      tested recognized these regions. Minor epitopes were also found scattered
      throughout the entire sequence. The reactivities of these minor epitopes to
      individual PBC sera were proportional to those of the major epitopes. All the
      epitopes were located in hydrophilic regions of E1alpha, and many of them were
      out of the known functional domains (TPP-binding domain, subunit interaction
      site, and phosphorylation sites) whose structures are phylogenically well
      conserved. Furthermore, the sequences of many epitopes appeared to be specific to
      humans. CONCLUSION: These observations suggest that determinant spreading might
      underlie the autoimmunity against Elalpha.

PMID- 14708898
TI  - Dietary effect of different high-fat diet on rat liver stereology.
AB  - BACKGROUND/AIMS: Dietary habits are considered to be responsible for a fatty
      liver. The aims of this work are to study the effects of different lipid sources
      on rat hepatic structure. METHODS: Twenty 21-day-old to 18-month-old male rats
      were fed one of the following diets: soybean oil, canola oil, lard and egg yolk
      (LE), or canola oil+lard and egg yolk (CA+LE). The blood serum triglyceride
      samples were analyzed. The following hepatic biometry and the stereology
      parameters were determined: densities of volume (V(v)) and surface (S(v)),
      absolute volume (V) and surface (S) of the hepatocytes (h), fat globules (g), and
      hepatic sinusoids (s), and numerical density of the hepatocytes (N(v)[h]).
      RESULTS: The largest values of V(v)[h], S(v)[h], V[h], and S[h] were found in the
      LE group. However, the largest values of V(v)[g], S(v)[g], and S[g] were found in
      the CA+LE group, and the smallest values of those parameters were found in the LE
      group. On the other hand, V[g] was larger in the CA+LE group. V(v)[s] and V[s]
      were larger in the LE group and smaller in the CA+ LE group. CONCLUSION: Long
      term administration of canola oil or soybean oil resulted in similar effects on
      hepatocytes, hepatic sinusoids, and fat globules. Long-term administration of
      lard and egg yolk attenuates hepatic fat accumulation and increases hepatic
      sinusoids. The administration of the canola oil and lard and egg yolk mixture
      increases hepatic fat accumulation, reducing the hepatic sinusoids.

PMID- 14708899
TI  - The hemodynamic effects of ATP in retrograde perfusion of the bivascularly
      perfused rat liver.
AB  - AIMS/BACKGROUND: In the sinusoidal bed the distribution of water is flow-limited,
      but it becomes partly barrier-limited when adenosine triphosphate (ATP) is
      introduced. This effect could be exerted either directly by ATP or by substances
      released from presinusoidal regions. Furthermore, portally infused ATP seems to
      be able to diffuse in the direction of the arterial bed. It is not known if this
      diffusion route is specific. Answers to these questions can be obtained from
      indicator-dilution experiments in retrograde perfusion. METHODS: Indicator
      dilution experiments, using [14C]sucrose and [3H]water, were conducted. Rat
      livers were perfused in the retrograde mode (hepatic vein+hepatic artery -->
      portal vein). RESULTS: When ATP was infused into the hepatic vein, the
      distribution of [3H]water remained essentially flow-limited. The infusion of ATP
      into the hepatic artery increased the sucrose and extra-sucrose spaces of the
      arterial bed, but infusion into the hepatic vein was without effect. CONCLUSIONS:
      The results indicate that the induction of barrier-limited distribution of
      [3H]water is not a direct effect of ATP. Furthermore, if the transhepatic
      diffusion of ATP can occur from presinusoidal regions to the arterial bed, as
      shown by previous work, a similar diffusion does not occur from postsinusoidal
      regions.

PMID- 14708900
TI  - Effect of apoE/ATP-containing liposomes on hepatic energy state.
AB  - BACKGROUND/AIMS: ATP-containing liposomes partially prevent ATP depletion in the
      cold-stored liver. As hepatocytes can specifically bind apoE, we investigated
      whether the addition of apoE to large (200 nm) ATP-containing liposomes increases
      their uptake by the liver and further improves hepatic energy stores. METHODS:
      Livers from fasted male Hartley guinea-pigs (231 +/- 3 g) were perfused for 90
      min under our standard conditions (Control, n = 6) or after a single bolus
      addition of plain liposomes (Lip, n = 6), ATP (5 micromol)-containing liposomes
      (ATP-Lip, n = 6) or apoE/ATP-containing liposomes (0.8 or 8mg apoE/g
      phospholipids; apoE1-Lip and apoE10-Lip, respectively, n = 6 in each group).
      Liposome uptake and its impact on energy and nitrogen metabolism were studied.
      RESULTS: At its highest concentration, apoE significantly increased liposome
      uptake (apoE10-Lip: - 9.17 +/- 0.69 vs apoE1-Lip: - 6.18 +/- 0.44 vs ATP-Lip: -
      6.40 +/- 0.88 nmol min(-1) g(-1) P < 0.05). This was associated with a
      significant increase in intrahepatic ATP (apoE10-Lip: 1033 +/- 137 vs apoE1-Lip:
      811 +/- 98 and ATP-Lip: 648 +/- 36 nmol g(-1); P < 0.05), which was restored to
      its level in non-perfused livers. Hepatic viability and nitrogen metabolism were
      not affected. CONCLUSIONS: Hepatic ATP content being a key factor in the
      maintenance of liver graft function, apoE/ATP-containing liposomes should be
      useful in liver preservation for transplantation.

PMID- 14708902
TI  - Mitochondrial DNA dysfunction in oncocytic hepatocytes.
AB  - Hepatic oncocytes with abundant granular, eosinophilic cytoplasm due to
      mitochondrial hyperplasia are seen in various chronic liver diseases,
      particularly chronic hepatitis and cirrhosis. Increased mitochondria in oncocytes
      are thought to be a compensatory mechanism for deficiencies in the hepatocellular
      respiratory chain, although the pathogenesis of these deficiencies has been
      uncertain. We selected seven cases of cirrhosis (six with oncocytes, one without)
      for the following analysis: histoenzymatic and immunohistochemical staining of
      several mitochondrial DNA (mtDNA)- and nuclear DNA (nDNA)-encoded respiratory
      chain enzymes; immunostaining using antibodies against double-strand-DNA (anti
      DNA) and against Ki-67 (a cell proliferation marker); and Southern blot analysis
      for mtDNA and nDNA. Eighty percent of oncocytes showed histoenzymatic and
      immunohistochemical deficiencies of cytochrome c oxidase and the mtDNA-encoded
      subunit I of complex IV, with preserved expression of nDNA-encoded succinate
      dehydrogenase and the iron-sulfur subunit of complex III (FeS). Cytoplasmic (but
      not nuclear) anti-DNA staining was partially or completely absent in
      approximately 50% of oncocytes. Three cases with oncocytes studied by Southern
      blot showed mtDNA reductions of 66%, 71%, and 85%. In conclusion, hepatic
      oncocytes demonstrate significant deficiencies of mtDNA and mtDNA-encoded
      respiratory chain enzymes. We propose that mtDNA depletion plays an important
      role in hepatocellular oncocytic transformation.

PMID- 14708901
TI  - Inhibition of nuclear factor kappaB and phosphatidylinositol 3-kinase/Akt is
      essential for massive hepatocyte apoptosis induced by tumor necrosis factor alpha
      in mice.
AB  - BACKGROUND/AIMS: Tumor necrosis factor (TNF)-alpha itself does not induce liver
      injury in normal mice or hepatocytes. Rather, this event, especially in vitro, is
      explained by the fact that the TNF-alpha/TNF receptor system not only triggers
      downstream signals leading to apoptosis but also induces an antiapoptotic pathway
      through the activation of nuclear factor (NF)-kappaB. The aim of this study was
      to determine whether inhibition of antiapoptotic pathways influences the
      susceptibility of mice to TNF-alpha. Here, we focused on the roles of NF-kappaB
      and phosphatidylinositol 3-kinase (PI3K)-regulated serine/threonine kinase Akt.
      METHODS: TNF-alpha was administered to BALB/c mice after treatment with an
      adenovirus expressing a mutant form IkappaBalpha (Ad5IkappaB), the PI3K inhibitor
      wortmannin, or both. Liver injury was assessed biochemically and histologically.
      The expression of Bcl-2 family members and caspase activity were examined.
      RESULTS: In the mice livers, treatment with Ad5IkappaB or the wortmannin
      suppressed the activation of NF-kappaB or Akt, respectively. Suppression of
      either NF-kappaB or Akt showed a slight increase in transaminase levels and focal
      liver cell death after TNF-alpha administration. However, in mice treated with
      both Ad5IkappaB and wortmannin, TNF-alpha administration resulted in massive
      hepatocyte apoptosis and hemorrhagic liver destruction in mice. The combination
      of Ad5IkappaB, wortmannin, and TNF-alpha markedly increased the activation of
      caspase-3 and -9, and activated caspase-8 to a lesser degree, suggesting that TNF
      alpha-induced hepatocyte apoptosis is dependent on type II cell death signaling
      pathway, probably through the mitochondria. Inhibition of the NF-kappaB and
      PI3K/Akt pathways had no effect on expression of Bcl-2 families. CONCLUSION: The
      inducible activation of NF-kappaB and constitutive activation of Akt regulate
      hepatocyte survival against TNF-alpha, which occurs independent of Bcl-2
      families.

PMID- 14708903
TI  - The change in renal replacement therapy on acute renal failure in a general
      intensive care unit in a university hospital and its clinical efficacy: a
      Japanese experience.
AB  - The aim of our study was to examine renal replacement therapies (RRT) that have
      been used for acute renal failure (ARF) in our intensive care unit (ICU) patients
      and to compare their outcomes. Sixteen patients who underwent intermittent
      hemodialysis (IHD), 14 patients who underwent continuous hemofiltration (CHF) in
      combination with IHD (CHF + IHD), and 38 patients who underwent continuous
      hemodiafiltration (CHDF) were evaluated. Regarding the effects of blood
      purification on hemodynamics and renal function, the percentage increase in blood
      pressure and percent rapid increase in urinary output were the greatest in the
      CHDF group. The hourly urinary output after the start of initial blood
      purification increased only in the CHDF group. The survival rate was
      significantly higher in the CHDF group. These results suggest that CHDF should be
      the first-line therapy for patients with ARF and that we are moving in the right
      direction regarding the application of RRT to treat ARF in ICU patients.

PMID- 14708904
TI  - Pharmacokinetics of nafamostat mesilate during continuous hemodiafiltration with
      a polyacrylonitrile membrane.
AB  - We studied the pharmacokinetics of nafamostat mesilate (NM) used as an
      anticoagulant in continuous hemodiafiltration (CHDF) with a polyacrylonitrile
      (PAN) membrane used as the hemofilter. Six patients undergoing CHDF for multiple
      organ dysfunction syndrome (MODS) were chosen as subjects. The inlet NM
      concentration measured 24 h after the start of CHDF was significantly greater
      than that after 1 h (P = 0.0431). No significant difference was observed between
      the outlet NM concentration and the ultrafilter concentration at 1 h or 24 h
      after the start of CHDF. However, concentrations at 24 h differed significantly
      from concentrations at 1 h at all sites. Significant correlation was observed
      between the dose of NM and the outlet NM concentration (P = 0.0475). No
      statistical correlation was observed between the dose of catecholamines and the
      outlet NM concentration (P = 0.0985). This study is the first to disclose a mild
      but significant time-dependent serum NM concentration in patients with MODS.

PMID- 14708905
TI  - Ascites from patients with encapsulating peritoneal sclerosis augments NIH/3T3
      fibroblast proliferation.
AB  - Encapsulating peritoneal sclerosis (EPS) remains one of the major causes of
      dropout in continuous ambulatory peritoneal dialysis by reducing ultrafiltration
      capacity. To demonstrate whether ascites from patients with EPS (EPS ascites) has
      fibroblast proliferation activity, we used NIH/3T3 fibroblasts to examine the
      effects of EPS ascites on fibroblast proliferation activity by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Encapsulating
      peritoneal sclerosis ascites dose-dependently augmented NIH/3T3 fibroblast
      proliferation. The protein kinase C inhibitors and the tyrosine kinase inhibitors
      partially inhibited the stimulatory effects of EPS ascites on fibroblast
      proliferation activity. In EPS ascites, levels of interleukin (IL)-1beta, IL-6,
      IL-8, transforming growth factor (TGF)-beta1, hepatocyte growth factor (HGF), and
      platelet-derived growth factor (PDGF)-AB were elevated. The treatment with IL
      1beta, HGF, TGF-beta1, and PDGF-AB alone or in combination at similar
      concentrations to those in EPS ascites exhibited small but significant fibroblast
      proliferation activities. We conclude that EPS ascites stimulate NIH/3T3
      fibroblast proliferation via protein kinase C and tyrosine kinase. The elevated
      cytokine and growth factors partly contribute to the EPS ascites-induced
      fibroblast proliferation.

PMID- 14708906
TI  - Who should be taking the blood pressure?
AB  - Given the variability of blood pressure, it is often difficult to make a
      diagnosis of hypertension or to evaluate the effect of treatment on the basis of
      single blood pressure readings in the office. To obtain multiple measurements one
      can either turn to ambulatory blood pressure monitoring or have the patient take
      his or her own pressure. Both approaches require the availability of reliable,
      validated devices. Currently, only some instruments which measure blood pressure
      oscillometrically at the upper arm can be recommended for self-measurements.
      Studies are in progress to assess the prognostic significance of self-measured
      blood pressure data.

PMID- 14708907
TI  - Home blood pressure measurement with oscillometric upper-arm devices.
AB  - The market for automated blood pressure measuring devices is growing rapidly.
      Many patients want to buy a device for blood pressure measurement at home and ask
      their physician for advice about which one to choose. In this article an overview
      is given of the different devices available for blood pressure measurement and
      possible pitfalls in the interpretation of measurements taken at home are pointed
      out. A second article will specifically address those devices that are used to
      take blood pressure measurements at the wrist.

PMID- 14708908
TI  - Oscillometric wrist blood pressure measuring devices.
AB  - Devices measuring blood pressure oscillometrically at the wrist are becoming more
      and more popular. These devices are small, easy to handle and can measure blood
      pressure without the need to undress. However, few of the wrist devices have been
      validated properly, i.e. according to internationally accepted protocols. In this
      article current literature on wrist blood pressure measuring devices is
      presented. The importance of positioning the wrist at heart level for accurate
      measurements is stressed.

PMID- 14708909
TI  - Cardiac and metabolic effects in patients who present with a multinodular goitre.
AB  - Twenty-six consecutive patients who presented with clinically euthyroid
      multinodular goitre were studied for an overnight fasting serum lipid profile and
      24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p <
      0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs
      controls (n = 15) while mean FT4 was not different from controls. Total serum
      HDL, LDL cholesterol and triglycerides were lower in patients but creatinine,
      ferritin and SHBG levels did not differ between patients and controls. The 24
      hour ambulatory continuous ECG recordings did not demonstrate significant
      differences in mean, minimal and maximal heart rate between the study and the
      control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also
      showed no differences between the two groups. Atrial fibrillation was absent in
      both the study and the control group. Premature atrial and ventricular complexes
      occurred equally frequently in both groups. Comparison of patients with a serum
      TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no
      differences. In conclusion, in consecutive patients who present with multinodular
      goitre, effects were found on the lipid profile, but not on the heart. It is
      argued that in this type of patients, cardiac effects depend on the degree of
      subclinical hyperthyroidism.

PMID- 14708910
TI  - F-18-fluorodeoxyglucose positron emission tomography in diagnosis and follow-up
      of patients with different types of vasculitis.
AB  - BACKGROUND: F-18-fluorodeoxyglucose (FDG) accumulates in inflammatory cells due
      to an increased metabolic rate. Therefore, FDG positron emission tomography (PET)
      represents a promising imaging technique in patients with vasculitis. The aim of
      this study was to assess the value of FDG PET in the diagnosis of different types
      of vasculitis. METHODS: The results of FDG PET performed because of suspected
      vasculitis or fever of unknown origin with results indicating vasculitis were
      reviewed. These results were compared with the final diagnosis, based on the
      American College of Rheumatology 1990 criteria. RESULTS: FDG PET was ordered
      because of suspected vasculitis in 20 patients, because of fever of unknown
      origin in two patients, and for follow-up of vasculitis in five patients.
      Fourteen patients were diagnosed with vasculitis (giant cell arteritis n = 5,
      polymyalgia rheumatica n = 2, polyarteritis nodosa n = 3, Takayasu n = 1, Churge
      Strauss n = 1, Wegener's granulomatosis n = 1, vasculitis skin n = 1), two
      patients were diagnosed with fibromuscular dysplasia and one patient had media
      necrosis of the aorta. In five patients no diagnosis could be reached. FDG PET
      results were considered to be true-positive in ten patients, true-negative in 14
      patients and false-negative in three patients resulting in a positive predictive
      value of 100% and a negative predictive value of 82%. CONCLUSIONS: FDG PET
      appears to be a promising new imaging technique in diagnosing and determining the
      extent of various forms of vasculitis. Furthermore, FDG PET may become a useful
      tool for evaluating the effect of treatment of vasculitis.

PMID- 14708911
TI  - Hypertension in neurofibromatosis.

PMID- 14708912
TI  - Unexpected survival from severe metformin-associated lactic acidosis.
AB  - Lactic acidosis is a recognised complication of the antihyperglycaemic biguanide
      agent metformin, especially in patients with renal failure. We report a case of
      severe lactic acidosis and hypothermia due to metformin treatment and renal
      impairment. The favourable outcome despite extremely unfavourable clinical signs
      and symptoms for survival after admission and initial treatment was unexpected.
      Specific aspects of the clinical course are addressed.

PMID- 14708913
TI  - Postpartum ovarian vein thrombosis: report of a case and review of literature.
AB  - Postpartum ovarian vein thrombosis (POVT) is an uncommon disease and it may
      complicate streptococcal group B infection of the vagina and endometrium.
      Obstruction of the right ureter is an uncommon complication of POVT. We present a
      case of POVT complicated by thrombus extension in the inferior vena cava and
      ureteral obstruction with urinary leakage, and outline the clinical presentation,
      radiological investigations useful in diagnosis and treatment of the disease
      process.

PMID- 14708914
TI  - Severe maternal respiratory distress due to the amniotic fluid embolism syndrome
      in a twin pregnancy.
AB  - A 28-year-old female with a twin pregnancy at 29 6/7 weeks who was having
      premature uterine contractions developed acute respiratory failure due to sudden
      pulmonary oedema requiring mechanical ventilation. No evidence for venous
      thromboembolism, pulmonary infection or myocardial infarction was found.
      Subsequently a mild coagulopathy and foetal distress developed. Ultrasonography
      revealed oligohydramnios of one of the foetuses. A Caesarean section was
      performed and postoperatively mother and babies had an uneventful clinical
      course. By exclusion of other causes, we diagnosed severe maternal acute
      respiratory distress due to the amniotic fluid embolism syndrome in a twin
      pregnancy.

PMID- 14708915
TI  - Palliative care at home. Dying at home: an increasingly important trend.

PMID- 14708916
TI  - Statistics can affect treatment decisions.

PMID- 14708917
TI  - Acupuncture and adverse effects.

PMID- 14708918
TI  - Acupuncture and adverse effects.

PMID- 14708919
TI  - Evidence sketchy on circumcision and cervical cancer link.

PMID- 14708920
TI  - Evidence sketchy on circumcision and cervical cancer link.

PMID- 14708921
TI  - Evidence sketchy on circumcision and cervical cancer link.

PMID- 14708922
TI  - Why not family medicine?

PMID- 14708923
TI  - A finger or tube in every orifice.

PMID- 14708924
TI  - Hemophilia during pregnancy.
AB  - QUESTION: A patient in my clinic, who is 10 weeks into her first pregnancy and is
      a known carrier of hemophilia B, is considering the advantages and disadvantages
      of antenatal tests and is especially worried about a vaginal delivery thatmight
      cause bleeding. How should I manage her pregnancy? ANSWER: Many female carriers
      of hemophilia were found to have lower-than-expected levels of plasma factors,
      which are thought to be due to X chromosome inactivation. Chorionic villous
      sampling is the preferred test to determine the sex of the fetus and whether a
      male infant is affected with hemophilia. Vaginal delivery is not contraindicated
      and has been proven during the last two decades to be as safe as cesarean
      section. Vacuum extraction should be avoided to minimize risk of intracranial
      hemolysis and severe cephalhematoma.

PMID- 14708925
TI  - Ophthaproblem. Retinopathy of prematurity.

PMID- 14708926
TI  - An approach to dyspnea in advanced disease.
AB  - INTRODUCTION: To describe an approach to assessment and treatment of dyspnea.
      SOURCES OF INFORMATION: New level I evidence can guide management of dyspnea in
      advanced illness. Assessment and use of adjuvant medications and oxygen relies on
      level II and III evidence. MAIN MESSAGE: Opioids are first-line therapy for
      managing dyspnea in advanced illness. They are safe and effective in reducing
      shortness of breath. Neuroleptics are useful adjuvant medications. Evidence does
      not support use of oxygen for every patient experiencing dyspnea; it should be
      tried for patients who do not benefit from first-line medications and
      nonmedicinal therapies. CONCLUSION: Opioids relieve dyspnea and are indicated as
      first-line treatment for dyspnea arising from advanced disease of any cause.

PMID- 14708928
TI  - Ethical issues in palliative care. Views of patients, families, and nonphysician
      staff.
AB  - OBJECTIVE: Much of what we know about ethical issues in palliative care comes
      from the perceptions of physicians and ethicists. In this study our goal was to
      hear other voices and to gain first-hand knowledge of the possibly contrasting
      views of patients, their families, nurses, volunteers, and other team members on
      end-of-life issues. DESIGN: Qualitative study using semistructured interviews.
      SETTING: Inpatient and consultation palliative care service of the Royal Victoria
      Hospital in Montreal, Que. PARTICIPANTS: Of 113 people interviewed, 13 were
      patients, 43 were family members, 32 were volunteers, 14 were nurses, and 11 were
      other staff. METHOD: Interviewers elicited subjects' perspectives on ethical
      issues. Content analysis was used to identify, code, and categorize themes in the
      data. MAIN FINDINGS: Communication difficulties and insufficient resources and
      staff were the most frequently mentioned problems in this palliative care
      setting. CONCLUSION: The findings of this study will help guide policy decisions
      and setting of educational priorities in end-of-life care, particularly regarding
      the importance of adequate communication.

PMID- 14708927
TI  - Lifestyle interventions for type 2 diabetes. Relevance for clinical practice.
AB  - OBJECTIVE: To review evidence from literature on type 2 diabetes pertinent to
      physical activity and diet and lifestyle modification, and to determine the
      relevance of this evidence to clinical practice. QUALITY OF EVIDENCE: Direct
      (level I) evidence supports interventions for physical activity and diet
      modification for primary prevention and management of type 2 diabetes. Few
      studies examine the effectiveness of primary health care providers' making such
      interventions. MAIN MESSAGE: Family physicians have an important role in
      identifying people at risk of developing type 2 diabetes and managing those
      diagnosed with the disease, yet they struggle to deliver practice-based
      interventions that promote sustainable behaviour change among their patients.
      CONCLUSION: It is evident that supporting patients to make changes in their
      physical activity and dietary habits can prevent onset of type 2 diabetes.
      Translating this finding into effective recommendations for clinical practice
      requires further effort and evaluation.

PMID- 14708929
TI  - Short report: ibuprofen versus glucosamine sulfate. Treating osteoarthritis pain.

PMID- 14708930
TI  - Residents' page.

PMID- 14708931
TI  - Bioethics and religions: religious traditions and understandings of morality,
      health, and illness.
AB  - For many individuals, religious traditions provide important resources for moral
      deliberation. While contemporary philosophical approaches in bioethics draw upon
      secular presumptions, religion continues to play an important role in both
      personal moral reasoning and public debate. In this analysis, I consider the
      connections between religious traditions and understandings of morality,
      medicine, illness, suffering, and the body. The discussion is not intended to
      provide a theological analysis within the intellectual constraints of a
      particular religious tradition. Rather, I offer an interpretive analysis of how
      religious norms often play a role in shaping understandings of morality. While
      many late 19th and early 20th century social scientists predicted the demise of
      religion, religious traditions continue to play important roles in the lives of
      many individuals. Whether bioethicists are sympathetic or skeptical toward the
      normative claims of particular religious traditions, it is important that
      bioethicists have an understanding of how religious models of morality, illness,
      and healing influence deliberations within the health care arena.

PMID- 14708932
TI  - Multicultural health care in practice. An empirical exploration of multicultural
      care in The Netherlands.
AB  - This study presents a first assessment of the challenges faced by Dutch health
      care providers dealing with the increasing cultural diversity in Dutch society.
      Qualitative interviews with 24 Dutch caregivers and policy-makers point to a
      number of important difficulties encountered when confronted with the growing
      diversity of patient populations. The study focuses explicitly on the challenges
      health care providers perceive in their direct interactions with patients. On the
      basis of the observations of the 24 respondents five strategies were formulated
      to improve the delivery of care in a multicultural environment. Their findings
      were further evaluated by confronting the empirical data with care-ethical
      notions (attentiveness, responsibility, competence, and responsiveness) and
      intercultural communication-theory.

PMID- 14708933
TI  - Requiring consent vs. waiving consent for medical records research: a Minnesota
      law vs. the U.S. (HIPAA) privacy rule.
AB  - The use of medical records in research can yield information that is difficult to
      obtain by other means. When such records are released to investigators in
      identifiable form, however, substantial privacy and confidentiality risks may be
      created. These risks become more common and more serious as medical records move
      to an electronic format. In 1996, the state of Minnesota enacted legislation with
      respect to consent requirements for the use of medical records in research. This
      legislation has been widely criticized because--it is claimed--it creates an
      unnecessary impediment to research. In this article, we show that these arguments
      rest upon misinterpretation and/or misrepresentation of the 1996 legislation. A
      consent requirement had actually been present in Minnesota since 1976 (though
      codified in a patient rights statute rather than a privacy statute). The 1996 law
      does not require specific consent, as often claimed, but rather only a general
      authorization. The campaign against the Minnesota legislation appears to have
      been motivated by concern with respect to the then impending federal privacy
      rule. The HIPAA rule, as enacted, is in fact less stringent with respect to
      consent than the Minnesota consent law. On the other hand, the Minnesota consent
      law has not been effectively applied or enforced. As we change the way we manage
      sensitive medical information, new efforts are needed to provide protection
      against the confidentiality risks in research. Patient consent is an important
      tool in this regard. New instrumentalities are needed to solicit and document
      consent.

PMID- 14708934
TI  - Persecutors or victims? The moral logic at the heart of eating disorders.
AB  - Eating Disorders, particularly anorexia and bulimia, are of immense contemporary
      importance and interest. News stories depicting the tragic effects of eating
      disorders command wide attention. Almost everybody in society has been touched by
      eating disorders in one way or another, and contemporary obsession with body
      image and diet fuels fascination with this problem. It is unclear why people
      develop eating disorders. Clinical and sociological studies have provided
      important information relating to the relational systems in which eating
      disorders are mainly found. This paper shows that their explanations are not
      conclusive and points out that the reasons why people develop eating disorders
      should not be found in the dysfunctional interactions occurring in both familial
      and social systems, but in the moral beliefs that underlie these interactions.
      Eating disorders are impossible to understand or explain, unless they are viewed
      in the light of these beliefs. A moral logic, that is a way of thinking of
      interpersonal relations in moral terms, gives shape to and justifies the clinical
      condition, and finds consistent expression in abnormal eating behaviour. The
      analysis offered here is not mainstream either in philosophy (eating disorders
      are in fact seldom the subject of philosophical investigation) or in clinical
      psychology (the methods of philosophical analysis are in fact seldom utilised in
      clinical psychology). However, this paper offers a important contribution to the
      understanding of such a dramatic and widespread condition, bringing to light the
      deepest reasons, which are moral in nature, that contribute to the explanation of
      this complex phenomenon.

PMID- 14708935
TI  - Utilitarian theories reconsidered: common misconceptions, more recent
      developments, and health policy implications.
AB  - Despite the prevalence of the terms utilitarianism and utilitarian in the health
      care and health policy literature, anecdotal evidence suggests that authors are
      often not fully aware of the diversity of utilitarian theories, their principles,
      and implications. Further, it seems that authors often categorically reject
      utilitarianism under the assumption that it violates individual rights. The
      tendency of act utilitarianism to neglect individual rights is attenuated,
      however, by the diminishing marginal utility of wealth and the disutility of a
      protest by those who are disadvantaged. In practice, act utilitarians tend to
      introduce moral rules and preserve traditional rules. At the same time, the
      tenability of rule utilitarianism is limited because it ultimately collapses into
      act utilitarianism or a deontological theory. Negative utilitarianism is a viable
      utilitarian variant only if we accept complete aversion to suffering, ie, if we
      disregard any forgone opportunities to increase pleasure. Finally, the adoption
      of preference utilitarianism requires us to accept the subjectivity of individual
      claims which may be perceived as unfair.

PMID- 14708936
TI  - Resource allocation in health care: health economics and beyond.
AB  - As resources in health care are scarce, managers and clinicians must make
      difficult choices about what to fund and what not to fund. At the level of a
      regional health authority, limited approaches to aid decision makers in shifting
      resources across major service portfolios exist. A participatory action research
      project was conducted in the Calgary Health Region. Throughfive phases of action,
      including observation of senior management meetings, as well as two sets of one
      on-one interviews and two focus groups, an approach to priority setting at the
      macro level within the health region was developed and implemented. The resulting
      macro level approach builds on the program budgeting and marginal analysis
      (PBMA)framework. Using a multi-disciplinary expert panel, about dollar 45M (CAN)
      was released for the 2002/03 fiscal year and made available for re-allocation to
      service growth areas and the deficit. Important qualitative themes from the
      managers and clinicians informed both process development and refinement. The
      approach developed here not only facilitated re-allocation of resources, but also
      drew in both clinicians and managers to work together on this challenging task.
      The approach is pragmatic, transparent and evidence based, and should have
      application elsewhere.

PMID- 14708937
TI  - The meaning of quality in health care: a conceptual analysis.
AB  - During the past three decades, there has been an ongoing debate on the quality of
      health care. Defining quality is an important part of it. This paper offers a
      review of definitions and a conceptual analysis in order to understand and
      explain the differences between them. The analysis results in a semantic rule,
      expressing the meaning of quality as an optimal balance between possibilities
      realised and a framework of norms and values. This rule is postulated as a formal
      criterion of meaning, e.g. when (correctly) applied people understand each other.
      The rule suits the abstract nature of the term "quality." Quality doesn't exist
      as such. It is constructed in an interaction between people. This interaction is
      guided by rules in order to transfer information, e.g. communicate on quality.
      The rule improves our ability to discuss the debate on quality and to develop a
      theory grounding actions such as quality assurance or quality improvement.

PMID- 14708938
TI  - Expression of nerve growth factor in human pancreatic beta cells.
AB  - Nerve growth factor (NGF) is an important modulator of rat pancreatic beta-cell
      physiology in vitro. In this study, we analysed the expression of NGF, TrkA and
      insulin in human pancreatic islets from normal, ductal adenocarcinoma and
      insulinoma-afflicted samples, using double immunofluorescent labelling and
      confocal microscopy. We found that in normal human pancreas, insulin and NGF are
      co-expressed in beta cells. Moreover, similar to previous observations in rat,
      the high affinity NGF receptor TrkA is also expressed in beta cells. Pancreatic
      beta cells in normal islets from adenocarcinoma and mucinous cystadenocarcinoma
      patients also expressed NGF. In 2 out of 15 exocrine tumour samples, NGF was
      detected also in the tissue surrounding the islets, while 2 out of 13
      adenocarcinoma tumours expressed this growth factor. In five insulinoma samples,
      we observed weaker immunofluorescent labelling of insulin and NGF in the
      neoplastic tissue, compared to the islets not afflicted by the tumour, which may
      be a consequence of increased hormone secretion rate. We demonstrate that human
      beta cells express TrkA and NGF. These findings are consistent with the
      hypothesis that NGF modulates insulin secretion through a paracrine/autocrine
      loop, similar to the one observed in cultured rat beta cells.

PMID- 14708939
TI  - Structural determinants of heparan sulphate modulation of GDNF signalling.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has many functions including
      regulation of kidney morphogenesis and of neuron growth and survival in the
      enteric, sensory and central nervous systems. Reports of GDNF being used against
      Parkinson's disease in human patients have sparked intense clinical interest in
      GDNF signalling. We recently showed that GDNF signalling requires cell surface
      heparan sulphate glycosaminoglycans (Barnett et al., 2002, J. Cell Sci. 115, 4495
      4503). Here we use exogenous modified heparins to determine those structural
      features required to inhibit GDNF signalling in ex vivo assays. 2-O-sulphate
      groups were found to impart high activity but were not absolute requirements for
      the inhibition of GDNF signalling. These findings may explain the similarities
      between the phenotypes of transgenic mice lacking GDNF and those lacking heparan
      sulphate 2-sulphotransferase, the enzyme responsible for achieving 2-O-sulphation
      of uronic acids in vivo.

PMID- 14708940
TI  - PDGF-BB induces expression of LTBP-1 but not TGF-beta1 in a rat cirrhotic fat
      storing cell line.
AB  - TGF-beta, a profibrogenic cytokine is predominantly secreted as a latent molecule
      complexed with one of the latent TGF-beta binding proteins (LTBP). Due to the
      proposed functions of LTBP-1 and -3 in regulating TGF-beta-bioavailability and 
      activity, we investigated the effects of PDGF-BB and TGF-beta1 on their
      expression levels in Cirrhotic fat storing cells (CFSC). CFSC basally express
      LTBP-1 and -3 and TGF-beta1. LTBP-1 colocalizes with LAP and the cells secrete
      some active TGF-beta1. Promoter studies showed no strong induction of the LTBP-1
      promoters after stimulation, although mRNA and protein levels were increased by
      PDGF-BB treatment without affecting TGF-beta1 expression. Vice versa, TGF-beta1
      treatment did not alter LTBP-1 expression while an autocrine induction was found.
      Our data indicate that LTBP-1 but not TGF-beta1 is induced by PDGF-BB and that
      TGF-beta1 autoinduction does not affect the expression of LTBP-beta1. This
      divergent regulation may represent an important mechanism for modulation of TGF
      beta bioavailability.

PMID- 14708941
TI  - Distribution of insulin like growth factor-1 (IGF-1) and its receptor in the
      intestines of the one-humped camel (Camelus dromedarius).
AB  - The distribution of insulin-like growth factor-1 (IGF-1) and its receptor in the
      gut of the one-humped camel (Camelus dromedarius) were studied by
      immunohistochemistry and quantitative receptor autoradiography. IGF-1-IR cells
      occurred mainly in the lamina propria and epithelium of the small intestine,
      while in the large intestine positive cells were seen in the columnar cells of
      the epithelial layer of colonic glands. IGF-I was also discernible in the
      muscularis externa of the intestines. Autoradiography revealed a higher
      concentration of receptors in the mucosa compared to the muscular layer. With
      regard to the mucosa, the highest density of receptors was discernible in the
      duodenum. Immunohistochemistry revealed the main sites of the receptors to be the
      lamina propria, epithelia of the crypts and the villi of intestines. Double
      immunofluorescence studies with combined antisera to IGF-I and its receptor
      showed that the ligand and its receptor usually occurred within the same cell in
      the mucosa. A few cells with varied profiles immunoreacted to either the ligand
      or the receptor but not to both. Cells with varied profiles immunoreacted to
      antiserum of the receptors but not to the ligand in the muscle layer. Thus IGF-1
      might be acting on its receptor via both an autocrine and paracrine modes in the
      camel mucosa. In the muscularis layer, IGF-1 may be acting by different
      mechanisms. Our data demonstrate that unlike all other mammals studied, the camel
      contains a high concentration of IGF-1 receptors in the duodenal mucosa compared
      to other parts of the camel gut. It also possesses a higher concentration of the
      receptor in its mucosa compared to the muscle layer. We speculate that this might
      be a significant feature necessary for the regenerative ability of the duodenal
      mucosa in the one-humped camel.

PMID- 14708942
TI  - HB-GAM/Pleiotrophin and Midkine are differently expressed and distributed during
      retinoic acid-induced neural differentiation of P19 cells.
AB  - HB-GAM/Pleiotrophin and Midkine (MK) are developmentally-regulated proteins with
      putative functions during cell growth and differentiation. Using the P19 cell
      which is a model to study the events associated with early development, we
      examined the expression and cellular localization of HB-GAM and MK during neural
      differentiation of P19 cells induced by retinoic acid (RA). The temporal
      expressions of HB-GAM and MK transcripts and both the levels and cellular
      localizations of the corresponding proteins appeared dramatically different. MK
      mRNA, already expressed in untreated P19 cells, was transiently increased by
      exposure to RA and then largely down regulated. More interestingly, HB-GAM which
      was not detected in untreated P19 cells was strongly expressed after 2 days of RA
      treatment and this expression persists throughout the duration of the culture
      suggesting that it could be involved in different aspects of this differentiation
      process.

PMID- 14708943
TI  - A 5'-distal element mediates vitamin D-inducibility of PDGF-A gene transcription.
AB  - Expression of the platelet-derived growth factor-A subunit (PDGF-A) is regulated
      to a significant degree by DNA elements located in the 5'-distal region of the
      gene. A potent basal enhancer (ACE66) located approximately 7 kb upstream of the
      transcription start site contains a number of half-sites for nuclear receptor
      binding, two of which are arranged in the form of direct repeat-3 motif that
      corresponds to a consensus vitamin D response element (VDRE). Electrophoretic
      mobility shift assays confirmed that the ACE66 sequence was recognized as a high
      affinity target for binding of heterodimers of recombinant vitamin D receptor
      (VDR) and its partner, retinoid-X receptor-alpha (RXRalpha). VDRE activity was
      localized by transient transfection analysis to a direct repeat-3 motif within
      the 5'-portion of the ACE66 element. Moreover, 1,25-(OH)2D3 was validated as a
      regulator of the endogenous PDGF-A gene by the vitamin D-stimulated upregulation
      of PDGF-A mRNA levels in a VDR-expressing clone of JEG-3 cells. Thus, PDGF-A
      represents a novel mitogenic target of 1,25-(OH)2D3 whose expression is induced
      via binding of hormone-activated VDR to a response element located far upstream
      of the transcription start site.

PMID- 14708944
TI  - Patent foramen ovale: paradoxical embolism and paradoxical data.

PMID- 14708945
TI  - Intracardiac echocardiographic guidance during transcatheter device closure of
      atrial septal defect and patent foramen ovale.
AB  - OBJECTIVES: To describe our experience with intracardiac echocardiographic (ICE)
      guidance during transcatheter device closure of atrial septal defect (ASD) and
      patent foramen ovale (PFO) and to describe a detailed stepwise approach for
      performing ICE examinations. PATIENTS AND METHODS: We reviewed the ICE results of
      all patients who underwent transcatheter device closure of ASD/PFO at the Mayo
      Clinic in Rochester, Minn, between October 2000 and November 2002. Conscious
      sedation was used, and all ICE studies were performed using a diagnostic
      ultrasound catheter. RESULTS: Ninety-four patients (47 male; median age, 51 years
      [range, 17-81 years]) underwent ICE during transcatheter device closure of
      ASD/PFO. Total procedure time was 128 minutes (range, 27-320 minutes). ICE
      identified a previously unrecognized anatomical diagnosis in 32 of 94 patients.
      An additional ASD or PFO was found in 16 patients; a redundant atrial septum or
      an atrial septal aneurysm was found in 12 patients. There were few ICE
      complications (4%): 3 patients developed atrial fibrillation, and 1 developed
      supraventricular tachycardia; of these 4, 2 resolved spontaneously, and 2
      required cardioversion with no recurrence. CONCLUSION: ICE provides anatomical
      detail of ASD/PFO and cardiac structures facilitating congenital cardiac
      interventional procedures. ICE eliminates major drawbacks related to the use of
      transesophageal echocardiographic guidance for transcatheter device closure of
      ASD/PFO, specifically problems related to airway management. Finally, ICE gives
      the interventional cardiologist the ability to control all aspects of imaging
      without relying on additional echocardiographic support. We believe that ICE
      should be considered the preferred imaging technique for guidance of
      transcatheter device closure of ASD/PFO in adults and larger pediatric patients.

PMID- 14708946
TI  - Transcatheter Amplatzer device closure of atrial septal defect and patent foramen
      ovale in patients with presumed paradoxical embolism.
AB  - OBJECTIVE: To review our experience with, and profile the safety and efficacy of,
      the Amplatzer PFO (patent foramen ovale) occluder (APO) and Amplatzer septal
      occluder (ASO) used to close PFO and/or atrial septal defect (ASD) in patients
      with paradoxical embolism (PE). PATIENTS AND METHODS: Between April 1998 and
      November 2002, 103 patients at the Mayo Clinic in Rochester, Minn, and
      Scottsdale, Ariz, mean age 52.4 years, with presumed PE (transient ischemic
      attack [n=22], stroke [n=77], or peripheral emboli [n=4]) underwent transcatheter
      device closure of PFO (n=81), ASD (n=12), and ASD/PFO (n=10) with 106 devices
      (APO [n=22] or ASO [n=84]). RESULTS: All devices deployed successfully, and no
      patients died. Procedural complications included atrial fibrillation (n=2),
      vessel injury (n=3), profound sinus node dysfunction (n=1), and device
      embolization with successful retrieval (n=1). At 3 months, 7 of 95 monitored
      patients had trivial residual shunt; at 12 months, 2 of 28 monitored patients had
      trivial residual shunt. Three patients had recurrent events--2 transient ischemic
      attacks and 1 retinal artery occlusion--at a mean +/- SD follow-up of 8.3 +/- 8.1
      months (range, 1-34 months). None of these 3 patients had residual shunt or
      evidence of intracardiac thrombus. The average annual recurrence of all events
      was 3.6% at 23 months. The overall mean +/- SD freedom from recurrence of all
      events was 98.9% +/- 1.2% and 83.8% +/- 10.2% at 12 and 29 months of follow-up,
      respectively. CONCLUSIONS: Transcatheter device closure of PFO and/or ASD with
      use of APO/ASO in patients with presumed PE is effective and safe. Recurrent
      events may occur in the absence of a residual shunt.

PMID- 14708947
TI  - Frequency, clinical characteristics, and respiratory parameters of
      hepatopulmonary syndrome.
AB  - OBJECTIVES: To determine the frequency and the clinical characteristics of
      hepatopulmonary syndrome (HPS) in cirrhotic candidates for orthotopic liver
      transplantation and to identify the major respiratory parameters predictive of
      the presence of changes in arterial oxygenation. PATIENTS AND METHODS: Patients
      underwent transthoracic contrast-enhanced echocardiography, pulmonary
      scintigraphy, pulmonary function test with diffusing capacity of lung for carbon
      monoxide (DLCO), and measurement of arterial blood gases. RESULTS: Fifty-six
      patients were studied. Twenty-five patients (45%) presented with intrapulmonary
      vascular dilatations, but only 9 (16%) fulfilled the criteria for HPS. The
      clinical or demographic characteristics considered did not differ in the patients
      with and without HPS. The DLCO value was significantly lower in patients with HPS
      (P=.01). However, 32 (80%) of 40 patients with low DLCO values did not fulfill
      the criteria for HPS. An alveolar arterial oxygen gradient (AaPO2) of more than
      20 mm Hg showed a higher diagnostic accuracy (91%) in the assessment of HPS than
      did the DLCO of less than 80% predicted (41%) and the AaPO2 of more than 15 mm Hg
      (71%). CONCLUSIONS: The AaPO2 proved to be a more reliable index than PaO2 and
      DLCO for the determination of changes in arterial oxygenation in HPS. The DLCO
      does not seem to be a good marker for HPS screening. Intrapulmonary vascular
      dilatations were frequent, even in patients who did not fulfill the criteria for
      HPS.

PMID- 14708948
TI  - Prevalence of human immunodeficiency virus testing in patients with hepatitis B
      and C infection.
AB  - OBJECTIVES: To determine the proportion of patients with hepatitis B virus (HBV)
      and hepatitis C virus (HCV) who are adequately assessed for human
      immunodeficiency virus (HIV) and to identify variables associated with absence of
      HIV testing. PATIENTS AND METHODS: We retrospectively reviewed the medical
      records of patients who had positive serologic test results for reactive HBV
      and/or HCV between January 1999 and December 1999 and were followed up at a
      general internal medicine clinic in East Harlem, NY. Data were collected on
      patient demographics, HIV risk factors, and other variables that might influence
      the physician's decision to test the patient for HIV. Primary outcomes were HIV
      tests performed and documented discussions of at-risk HIV behavior. RESULTS: The
      HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the
      141 patients with reactive HBV and/or HCV serologic test results. Predictors of
      HIV testing on multivariate logistic regression were age younger than 50 years
      (odds ratio [OR], 25; 95% CI, 13-3.8), male sex (OR, 1.6; 95% CI, 1.1-2.2), and
      having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9). Injection
      drug use was not significantly associated with HIV testing. CONCLUSIONS: Although
      HBV and HCV have clear epidemiological links with HIV, this study shows that a
      high percentage of these patients are not being tested. Although some of the
      factors associated with lack of testing were identified, further studies on the
      barriers to HIV testing are needed to reveal potential approaches to increase
      rates of HIV testing in this high-risk population.

PMID- 14708949
TI  - Primer on medical genomics. Part XI: Visualizing human chromosomes.
AB  - In the past century, various methods to visualize human chromosomes were
      discovered. Chromosome analyses provide an overall view of the human genome that
      cannot be achieved with any other approach. The methods to visualize chromosomes
      include various techniques to produce bands along chromosomes, specialized
      procedures for specific disorders, and fluorescent-labeled DNA for targeted loci.
      Cytogenetic methods guide the study of the relationship between chromosome
      structure and gene function. They also aid in mapping locations of genes and
      identifying chromosome anomalies associated with medical disorders. The clinical
      diagnosis, prognosis, and response to treatment can be established for many
      malignant diseases. Cytogenetic methods provide an important diagnostic tool for
      clinical practice.

PMID- 14708950
TI  - Renal cell carcinoma with acrometastasis and scalp metastasis.

PMID- 14708951
TI  - Patent foramen ovale and stroke.
AB  - A patent foramen ovale (PFO) is a frequent remnant of embryological development
      with clinical importance in thromboembolism, paradoxical embolism, stroke,
      platypnea-orthodeoxia, decompression sickness, and migraine headache. The
      proposed mechanisms of stroke with PFO include paradoxical embolization, in situ
      thrombosis within the canal of the PFO, associated atrial arrhythmias, and
      concomitant hypercoagulable states. Prospective trials using aspirin treatment to
      reduce recurrent stroke showed a significant recurrence of neurologic events in
      patients with a PFO and atrial septal aneurysm. Use of warfarin anticoagulation
      does not further reduce recurrent stroke rates compared with antiplatelet
      therapy. Both surgical and catheter-based modes of closure have been shown to
      decrease the rate of subsequent embolic events substantially. Successful closure,
      defined by transesophageal echocardiography, appears to predict freedom from
      subsequent embolic events. To our knowledge, no randomized trials comparing
      anticoagulation with surgical or catheter-based closure have been performed.

PMID- 14708952
TI  - Phosphorus nutrition and the treatment of osteoporosis.
AB  - Bone mineral consists of calcium phosphate, and phosphorus is as important as
      calcium in supporting bone augmentation and maintenance. Although typical adult
      diets contain abundant phosphorus, 10% to 15% of older women have intakes of less
      than 70% of the recommended daily allowance. When these women take high-dose
      calcium supplements that consist of the carbonate or citrate salts, all their
      food phosphorus may be bound and hence unavailable for absorption. Current
      generation anabolic agents for treating osteoporosis require positive phosphorus
      balances of up to 90 mg/d. Attention to the nutritional adequacy of the diets of
      such patients is essential if they are to realize the full potential of such
      therapies. A calcium phosphate supplement may be preferable to the usual
      carbonate or citrate salts because its phosphate serves to spare food phosphorus.

PMID- 14708953
TI  - Cardiovascular disease resulting from a diet and lifestyle at odds with our
      Paleolithic genome: how to become a 21st-century hunter-gatherer.
AB  - Our genetic make-up, shaped through millions of years of evolution, determines
      our nutritional and activity needs. Although the human genome has remained
      primarily unchanged since the agricultural revolution 10,000 years ago, our diet
      and lifestyle have become progressively more divergent from those of our ancient
      ancestors. Accumulating evidence suggests that this mismatch between our modern
      diet and lifestyle and our Paleolithic genome is playing a substantial role in
      the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic
      cardiovascular disease. Until 500 generations ago, all humans consumed only wild
      and unprocessed food foraged and hunted from their environment. These
      circumstances provided a diet high in lean protein, polyunsaturated fats
      (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber,
      vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical
      and anthropological studies show hunter-gatherers generally to be healthy, fit,
      and largely free of the degenerative cardiovascular diseases common in modern
      societies. This review outlines the essence of our hunter-gatherer genetic legacy
      and suggests practical steps to re-align our modern milieu with our ancient
      genome in an effort to improve cardiovascular health.

PMID- 14708954
TI  - Hand hygiene: a frequently missed lifesaving opportunity during patient care.
AB  - Health care-associated infections constitute one of the greatest challenges of
      modern medicine. Despite compelling evidence that proper hand washing can reduce
      the transmission of pathogens to patients and the spread of antimicrobial
      resistance, the adherence of health care workers to recommended hand-hygiene
      practices has remained unacceptably low. One of the key elements in improving
      hand-hygiene practice is the use of an alcohol-based hand rub instead of washing
      with soap and water. An alcohol-based hand rub requires less time, is
      microbiologically more effective, and is less irritating to skin than traditional
      hand washing with soap and water. Therefore, alcohol-based hand rubs should
      replace hand washing as the standard for hand hygiene in health care settings in
      all situations in which the hands are not visibly soiled. It is also important to
      change gloves between each patient contact and to use hand-hygiene procedures
      after glove removal. Reducing health care-associated infections requires that
      health care workers take responsibility for ensuring that hand hygiene becomes an
      everyday part of patient care.

PMID- 14708955
TI  - 61-year-old woman with shortness of breath after surgery.

PMID- 14708956
TI  - Inappropriate medications for elderly patients.
AB  - The use of medications is common in elderly persons, and this population has the
      highest risk of medication-related problems. Elderly persons are more susceptible
      to the effects of various medications for a number of reasons. It is well known
      that polypharmacy is one of the most serious problems in caring for elderly
      persons; however, many of these patients continue to receive medications that
      have an increased risk of causing harm. In 1991, an important article was
      published about inappropriate medication use in the elderly population. This
      article raised awareness of the problem and presented explicit criteria for
      determining which medications were inappropriate for elderly patients residing in
      long-term care facilities. This list of drugs is still used for evaluating
      medications taken by elderly persons and for determining whether satisfactory
      prescribing practices are being used. We reviewed the medications described as
      inappropriate for elderly persons and searched the scientific literature to
      determine whether evidence exists to defend or refute the labeling of particular
      drugs. At times, evidence was difficult to find, and many of the original studies
      were dated. For most medications listed as inappropriate, we found evidence to
      support these designations.

PMID- 14708957
TI  - Syndromic immunodeficiencies: genetic syndromes associated with immune
      abnormalities.
AB  - In syndromic immunodeficiencies, clinical features not directly associated with
      the immune defect are prominent. Patients may present with either infectious
      complications or extra-immune medical issues. In addition to the immunologic
      abnormality, a wide range of organ systems may be affected. Patients may present
      with disturbances in skeletal, neurologic, dermatologic, or gastrointestinal
      function or development. These conditions can be caused by developmental
      abnormalities, chromosomal aberrations, metabolic disorders, or teratogens. For a
      number of these conditions, recent advances have resulted in an enhanced
      understanding of their genetic basis. The finding of immune deficits in a number
      of defined syndromes with congenital anomalies suggests that an underlying
      genetic syndrome should be considered in those patients in whom a significant non
      immune feature is present.

PMID- 14708958
TI  - Platelet-activating factor, a pleiotrophic mediator of physiological and
      pathological processes.
AB  - Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with
      diverse pathological and physiological effects. This bioactive phospholipid
      mediates processes as diverse as wound healing, physiological inflammation,
      apoptosis, angiogenesis, reproduction and long-term potentiation. Recent progress
      has demonstrated the participation of MAP kinase signaling pathways as modulators
      of the two critical enzymes, phospholipase A2 and acetyltransferase, involved in
      the remodeling pathway of PAF biosynthesis. The unregulated production of
      structural analogs of PAF by non-specific oxidative reactions has expanded this
      superfamily of signaling molecules to include "PAF-like" lipids whose mode of
      action is identical to that of authentic PAF. The action of members of this
      family is mediated by the PAF receptor, a G protein-coupled membrane-spanning
      molecule that can engage multiple signaling pathways in various cell types.
      Inappropriate activation of this signaling pathway is associated with many
      diseases in which inflammation is thought to be one of the underlying features.
      Inactivation of all members of the PAF superfamily occurs by a unique class of
      enzymes, the PAF acetylhydrolases, that have been characterized at the molecular
      level and that terminate signals initiated by both regulated and unregulated PAF
      production.

PMID- 14708959
TI  - What is the role of fluoroquinolones in intensive care?
AB  - Fluoroquinolones are a class of antibiotics that are widely used in the treatment
      of a number of severe infections frequently observed in intensive care units
      (ICU). From a pharmacodynamic point of view, the optimal conditions for
      guaranteeing clinical recovery and preventing the occurrence of resistance to
      this class of antibiotics are represented by the ratios of C(max)/MIC > 12.2 and
      AUC(24h)/MIC equal to 100-125 hours for Gram-negative bacteria, and about 30-40
      hours for Gram-positive cocci. Taking this into consideration, the
      pharmacokinetics and pharmacodynamics shown in healthy volunteers suggest that
      with the use of standard doses of the various fluoroquinolones, an optimal
      AUC(free)/MIC ratio for Gram-negative bacteria may be ensured with a minimum
      inhibitory concentration (MIC) < 0.25-0.5 mg/L and for Gram-positive bacteria
      with an MIC < 0.5-1 mg/L. The need to increase the dosage, or to combine them
      with other antibiotics is therefore recognized, when it is necessary to ensure
      adequate coverage of intermediately sensitive microorganisms (MIC 1-2 mg/L). In
      addition, patients recovered in the ICU often present some peculiar
      pathophysiological conditions that increase the distribution volume and/or the
      renal clearance of the drug. Thus it is likely that in this situation it would be
      reasonable to increase daily dosages, independent of the in vitro pattern of drug
      sensitivity (e.g. 500 mg b.i.d. for levofloxacin). Data from various clinical and
      pharmacological studies suggesting a potential role for fluoroquinolones both in
      monotherapy and combination therapy in the treatment of different clinically
      severe conditions are presented and discussed. This offers the dual opportunity
      to evaluate the role of quinolones as an alternative to aminoglycosides in
      combination with a beta-lactam and, at the same time, to consider their use in a
      periodic rotation program of anti-Gram-negative antibiotic therapy when there is
      a high risk of resistance selection, such as in the ICU. In conclusion, the role
      of fluoroquinolones in the treatment of multiple infectious diseases, such as
      bacteremia/sepsis, pneumonia and severe urinary tract infections in an
      environment such as the ICU is growing stronger, while there are convincing data
      indicating that these molecules might play a role in the treatment of meningitis
      in the near future.

PMID- 14708960
TI  - What is the role of glycopeptides in intensive care?
AB  - Bacterial infections are the major cause of illness and death in the intensive
      care unit (ICU). In general, each unit is in itself a high risk environment for
      infections, simultaneously containing many diverse factors that favor the spread
      of clinically evident and generally serious infections: the constant presence of
      serious concomitant diseases, the frequent use of invasive diagnostic methods and
      procedures, the elevated selective pressure caused by multiple and prolonged
      antibiotic treatment on endogenous and environmental microbial flora.
      Notwithstanding the fact that the bacterial epidemiology of the ICU varies
      slightly in different countries and in different ICUs, in the last 15 years a
      general and progressive increase in the etiology of Gram-positive aerobic
      bacteria has been observed. Currently, Staphylococcus aureus is the etiologic
      agent most frequently responsible for infections in the ICU; S. aureus +
      coagulase-negative Staphylococcus (CoNS) + Enterococcus are responsible for more
      than 60% of infections. More recent data confirm that next to modifications in
      bacterial etiology in the ICU, the most alarming phenomenon is the methicillin
      resistance of S. aureus (MRSA). The high percentage of multi-resistance compels
      us to reconsider therapy relative to the choice of antibiotics to use and, in
      particular, raises the question of possibly selecting the class of glycopeptides,
      alone or in combination, as the choice of treatment every time that an infection
      is caused by a Gram-positive microorganism. The use of glycopeptides, as with all
      antibiotics, must be evaluated in a suitable manner with the objective of
      limiting the selective pressure on resistant bacterial flora caused by their use.
      It is widely understood that inappropriate use of antibiotics, such as selecting
      an antibacterial agent with an inadequate spectrum that is thus ineffective,
      determines an increase in the mortality rate compared to using an agent with an
      appropriate spectrum of activity.

PMID- 14708961
TI  - What is the role of streptogramins in intensive care?
AB  - The combination of two injectable streptogramins, quinupristin/dalfopristin,
      provides a new pharmacological choice proven to be therapeutically efficacious
      against most Gram-positive, multi-resistant microorganisms. They have been shown
      to be efficacious above all in critically ill patients hospitalized in intensive
      care who have unique alterations in homeostasis that makes tissue penetration of
      various pharmacological antimicrobials difficult. In cases of infection localized
      in difficult-to-treat sites, the combination with other drugs, such as cefepime,
      a glycopeptide or linezolid, is able to potentiate the action of the
      streptogramin with positive results which allow resolution of the illness. In
      this article, we review data from the literature on the use of
      quinupristin/dalfopristin in the treatment of Gram-positive, multi-resistant
      infections in critically ill patients.

PMID- 14708962
TI  - Human hyalohyphomycoses: a review of human infections due to Acremonium spp.,
      Paecilomyces spp., Penicillium spp., and Scopulariopsis spp.
AB  - Human infections due to opportunistic molds are on the rise. This is due to
      recent advances in medical technology that have led to increased numbers of
      patients who are immunosuppressed, receiving broad-spectrum antibiotics, or have
      indwelling medical devices. In this article, human infections caused by four
      hyalohyphomycoses, Acremonium spp., Paecilomyces spp., Penicillium spp., and
      Scopulariopsis spp., will be reviewed. Specific areas of focus will include the
      epidemiology, mycology, clinical presentations, and treatment options for each of
      these four hyaline molds.

PMID- 14708963
TI  - Scedosporium species infections and treatments.
AB  - Scedosporium species are now increasingly isolated from immunocompromised and
      immunocompetent patients. Unfortunately, Scedosporium species infections are
      generally resistant to amphotericin B, and S. prolificans strains are
      particularly resistant to presently-available antifungal agents. Here we review
      the microbiology, expanding epidemiology, numerous clinical presentations, and
      diagnostic tools available for Scedosporium species infections. Finally, we
      detail the available in vitro, animal model, and clinical data on the treatment
      of Scedosporium species infections with special emphasis on the role of newer
      antifungal therapies for these recalcitrant infections.

PMID- 14708964
TI  - Infections caused by Fusarium species.
AB  - Fusariosis, an emerging opportunistic mycosis caused by Fusarium species, carries
      a high mortality rate in immunocompromised patients. The dismal prognosis of
      patients with fusariosis is aggravated by the limited therapeutic options. Here
      we give an overview of the epidemiology, pathogenesis, clinical manifestations,
      antifungal susceptibility and management of fusariosis.

PMID- 14708965
TI  - Epidemiology, clinical manifestations, and therapy of infections caused by
      dematiaceous fungi.
AB  - The dematiaceous (brown-pigmented) fungi are a large and heterogenous group of
      moulds that cause a wide range of diseases including phaeohyphomycosis,
      chromoblastomycosis, and eumycotic mycetoma. Among the more important human
      pathogens are Alternaria species, Bipolaris species, Cladophialophora bantiana,
      Curvularia species, Exophiala species, Fonsecaea pedrosoi, Madurella species,
      Phialophora species, Scedosporium prolificans, Scytalidium dimidiatum, and
      Wangiella dermatitidis. These organisms are widespread in the environment, being
      found in soil, wood, and decomposing plant debris. Cutaneous, subcutaneous, and
      corneal infections with dematiaceous fungi occur worldwide, but are more common
      in tropical and subtropical climates. Infection results from traumatic
      implantation. Most cases occur in immunocompetent individuals. Dematiaceous
      moulds are also important causes of invasive sinusitis and allergic fungal
      sinusitis. Infection is thought to follow inhalation. Although cerebral infection
      is the commonest form of systemic phaeohyphomycosis, other localized deep forms
      of the disease, such as arthritis, and endocarditis, have been reported.
      Disseminated infection is uncommon, but its incidence is increasing, particularly
      among immunocompromised individuals. Scedosporium prolificans is the most
      frequent cause. A number of dematiaceous fungi are neurotropic, including
      Cladophialophora bantiana, Ramichloridium mackenziei, and Wangiella dermatitidis.
      Although cases have occurred in immunocompromised persons, cerebral
      phaeohyphomycosis is most common in immunocompetent individuals with no obvious
      risk factors. Most forms of disease caused by dematiaceous fungi require both
      surgical and medical treatment. Itraconazole is currently the most effective
      antifungal agent for chromoblastomycosis and subcutaneous phaeohyphomycosis,
      while ketoconazole remains useful for mycetoma. Extensive surgical debridement
      combined with amphotericin B treatment is recommended for chronic invasive
      sinusitis. Long-term treatment with itraconazole has led to improvement or
      remission in some patients that had failed to respond to amphotericin B. Allergic
      fungal sinusitis requires surgical removal of impacted mucin combined with
      postoperative oral corticosteroids. Antifungal treatment is not usually of
      benefit, but post-operative itraconazole may reduce the need for reoperation. The
      clinical outcome of cerebral and other deep-seated forms of phaeohyphomycosis is
      dismal, with long-term survival being reported only when complete surgical
      resection of discrete lesions is possible. The development of new antifungal
      agents and combination treatment may help to improve the management of these
      infections.

PMID- 14708966
TI  - Development of new strategies to prevent type 1 diabetes: the role of animal
      models.
AB  - Type 1 diabetes is an immune-mediated disease typically preceded by a long
      preclinical stage during which a growing number of islet-cell-specific
      autoantibodies appear in the serum. Although antigen-specific T lymphocytes and
      cytokines rather than these autoantibodies are the likely executors of beta-cell
      destruction, these autoantibodies reflect the existence of autoimmunity that
      targets islet beta-cells. Abrogation of this autoimmunity during the preclinical
      stage would be the key to the prevention of type 1 diabetes. However, the quest
      of protecting islet-cells from the immune attack requires detailed knowledge of
      mechanisms that control islet-inflammation and beta-cell-destruction, and of
      mechanisms that control immune tolerance to peripheral self-antigens in general.
      This knowledge can only be obtained through further innovative research in
      experimental animal models. In this review, we will first examine how research in
      non-obese diabetic mice has already led to promising new strategies of diabetes
      prevention now being tested in human clinical trials. Thereafter, we will discuss
      how recent advances in understanding the mechanisms that control immune response
      to peripheral self-antigens such as beta-cell antigens may help to develop even
      more selective and effective strategies to prevent diabetes in the future.

PMID- 14708967
TI  - Mechanobiology and diseases of mechanotransduction.
AB  - The current focus of medicine on molecular genetics ignores the physical basis of
      disease even though many of the problems that lead to pain and morbidity, and
      bring patients to the doctor's office, result from changes in tissue structure or
      mechanics. The main goal of this article is therefore to help integrate mechanics
      into our understanding of the molecular basis of disease. This article first
      reviews the key roles that physical forces, extracellular matrix and cell
      structure play in the control of normal development, as well as in the
      maintenance of tissue form and function. Recent insights into cellular
      mechanotransduction--the molecular mechanism by which cells sense and respond to
      mechanical stress--also are described. Re-evaluation of human pathophysiology in
      this context reveals that a wide range of diseases included within virtually all
      fields of medicine and surgery share a common feature: their etiology or clinical
      presentation results from abnormal mechanotransduction. This process may be
      altered by changes in cell mechanics, variations in extracellular matrix
      structure, or by deregulation of the molecular mechanisms by which cells sense
      mechanical signals and convert them into a chemical or electrical response.
      Molecules that mediate mechanotransduction, including extracellular matrix
      molecules, transmembrane integrin receptors, cytoskeletal structures and
      associated signal transduction components, may therefore represent targets for
      therapeutic intervention in a variety of diseases. Insights into the mechanical
      basis of tissue regulation also may lead to development of improved medical
      devices, engineered tissues, and biologically-inspired materials for tissue
      repair and reconstruction.

PMID- 14708968
TI  - The iron hypothesis of atherosclerosis and its clinical impact.
AB  - The iron hypothesis as an alternative explanation for the gender difference in
      the incidence and mortality of atherosclerosis has provoked increased debates and
      public health concerns. In this review we summarize the historical and recent
      literature on the iron hypothesis and discuss several related clinical issues and
      their implications. Apart from misconstruction of study populations, lack of a
      good method to reflect the iron contents of tissues may be the major factor for
      causing inconsistent results from epidemiological studies. Published data from 11
      countries clearly indicate that the mortality from cardiovascular diseases is
      correlated with liver iron. We propose that redox-active iron in tissue is the
      atherogenic portion of total iron stores. Recently developed magnetic resonance
      imaging techniques in combination with Fe chelators may allow future studies to
      examine this component of body iron in lesions and the whole body. Several
      clinical situations characterized by increased iron stores have been proposed as
      'human models' suitable for further tests of the iron hypothesis. Patients with
      end-stage renal disease may be the most unique cohort, having significant
      increases in their iron stores, low-density lipoprotein (LDL) oxidation, and
      cardiovascular events. Other patient groups may be well suited for specific
      studies of different atherogenic events. With a better understanding of iron
      driven oxidative damage, well controlled and effectively designed studies on
      these models will finally bring us to the truth of the iron hypothesis.

PMID- 14708969
TI  - Unheralded sudden cardiac death: do autonomic tone and thrombosis interact as key
      factors in aetiology?
AB  - Unheralded sudden cardiac death is a personal and family tragedy that continues
      to elude research-based progress on aetiology or prevention. Instinctive links
      between autonomic imbalance, sympathetic activation and serious arrhythmia are
      longstanding and backed by many observational reports. However the role of the
      more familiar mechanisms of coronary occlusion and thrombus formation are
      underplayed. Sympathetic overactivity may also mediate sudden death through
      precipitation of vasospasm; platelet activation and inhibition of endogenous
      fibrinolysis as well as the propagation of arrhythmia. The integration of
      autonomic, thrombotic and vascular tone may be the key to better understanding of
      the individual process of unheralded sudden cardiac death. In this review we
      analyse the evidence for this hypothesis.

PMID- 14708970
TI  - Effects of bosentan on cellular processes involved in pulmonary arterial
      hypertension: do they explain the long-term benefit?
AB  - Pulmonary arterial hypertension is a rapidly progressing disease characterized by
      an over- expression of endothelin. In addition to its potent pulmonary
      vasoconstrictor effects, endothelin has been shown to produce many of the
      aberrant changes, such as hypertrophy, fibrosis, inflammation, and neurohormonal
      activation that underlie the shortened life span in pulmonary arterial
      hypertensive patients. The fact that endothelin expression correlates
      significantly with disease severity and outcome in these patients suggests that
      endothelin, through binding to both ETA and ETB receptor subtypes, is a key
      causative agent in the pathophysiology of pulmonary arterial hypertension. The
      orally active dual endothelin receptor antagonist bosentan competitively
      antagonizes the binding of endothelin to both endothelin receptor subtypes with
      high affinity and specificity. In animal models relevant for the pathophysiology
      of pulmonary hypertension, bosentan not only causes selective pulmonary
      vasodilation, but also prevents vascular hypertrophy and cardiac remodeling,
      attenuates pulmonary fibrosis, decreases vascular inflammation, and blunts
      neurohormonal activation. These experimental data may explain the effects on
      disease progression and the long-term benefit observed with bosentan in pulmonary
      arterial hypertension.

PMID- 14708971
TI  - New insights into estrogen receptor function in human breast cancer.
AB  - An important new concept associated with estrogen receptor (ER) function in
      breast cancer is that ER status/ phenotype is multifaceted. In particular, the
      two full-length, ligand binding ERs (ER-alpha and ER-beta) and possibly multiple
      variant isoforms of ER must be considered. In addition, cross-talk factors that
      can influence ER activity in a ligand independent fashion and factors downstream
      of the ER, including coactivators and corepressors, clearly have important roles
      in ER function. Their careful evaluation in addition to ER status will be
      necessary to more fully understand the etiology of breast cancer and the changes
      occurring in estrogen signaling during breast tumorigenesis and breast cancer
      progression. Such knowledge is necessary to have a significant impact on better
      prevention and treatment strategies for human breast cancer.

PMID- 14708972
TI  - The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate
      dehydrogenase.
AB  - It is well documented that disturbances in mitochondrial function are associated
      with rare childhood disorders and possibly with many common diseases of ageing,
      such as Parkinson's disease and dementia. There has also been increasing evidence
      linking mitochondrial dysfunction with tumorigenesis. Recently, heterozygous
      germline mutations in two enzymes of the Krebs tricarboxylic acid cycle (TCA
      cycle) have been shown to predispose individuals to tumours. The two enzymes,
      fumarate hydratase (FH) and succinate dehydrogenase (SDH), are ubiquitously
      expressed, playing a vital role in adenosine triphosphate (ATP) production
      through the mitochondrial respiratory chain. Germline mutations in FH are
      associated with leiomyomatosis and renal cell carcinoma, whilst SDH mutations are
      associated with predisposition to paraganglioma (PGL) and phaeochromocytoma
      (PCC). At present, there are few data to explain the pathway(s) involved in this
      predisposition to neoplasia through TCA cycle defects. We shall review the
      mechanisms by which mutations in FH and SDH might play a role in tumorigenesis.
      These include pseudo-hypoxia, mitochondrial dysfunction and impaired apoptosis,
      oxidative stress and anabolic drive. All of these mechanisms are currently poorly
      defined. To date, FH and SDH mutations have not been reported in non-familial
      leiomyomata, renal cancers, PCCs or PGLs. It remains entirely possible, however,
      that the underlying mechanisms of tumorigenesis in these sporadic tumours are the
      same as those in the Mendelian syndromes.

PMID- 14708973
TI  - A recombination event, induced in ovo, between a low passage infectious
      bronchitis virus field isolate and a highly embryo adaptedvaccine strain.
AB  - The possibility of genomic recombination among different strains of infectious
      bronchitis virus (IBV) was examined in eve by coinfecting specific pathogen free
      embryonating chicken eggs with commonly used, embryo-adapted vaccine strains of
      IBV (Arkansas, Massachusetts, and Connecticut), and a Delaware-072-like field
      virus isolated from a layer farm in Minnesota. Recombination was observed between
      th e Massachusetts and the Delaware-072-like strains of the virus. The
      recombination event was assessed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) using a combination of specific primers designed to flank a
      known recombination hot spot of the viral genomic sequence that codes for the S1
      subunit of the spike envelope protein. The use of these primers allowed the
      detection of viruses that have undergone recombination around this hot spot.
      Cloning and sequencing of the RT-PCR product obtained was performed to confirm
      these results.

PMID- 14708974
TI  - Nitric oxide synthase expression in the endothelium of pulmonary arterioles in
      normal and pulmonary hypertensive chickens subjected to chronic hypobaric
      hypoxia.
AB  - To determine whether or not exposure to chronic hypoxia and subsequent
      development of pulmonary hypertension syndrome (PHS) induce alterations in
      endothelial nitric oxide (NO) production in broiler's pulmonary vascular bed of
      broilers, we studied the expression of nitric oxide synthase enzyme in pulmonary
      endothelial cells by a nicotinamide adenine dinucleotide phosphate (NADPH)
      diaphorase histochemical staining reaction. For this purpose, 60 broilers of
      three different ages (17, 30, and 42 days) were used. The animals were
      distributed in two groups: a) 30 healthy (nonhypertensive) broilers and b) 30
      chicks with PHS. All broilers in group b had fewer NADPH-diaphorase-positive
      endothelial cells in arterioles than did the nonhypertensive broilers. These
      differences were highly significant (P < 0.01). These results demonstrate for,
      the first time in broilers, that hypoxia-induced pulmonary hypertension is
      associated with a decrease of endothelial-derived NO expression in pulmonary
      vessels.

PMID- 14708975
TI  - Evaluation of the protection conferred by commercial vaccines against the
      California 99 isolate of infectious bronchitis virus.
AB  - An infectious bronchitis virus (IBV) was isolated from commercial broilers from
      the state of California exhibiting respiratory distress, inflamed tracheas,
      airsaculitis, and edematous lungs. After reverse transcriptase-polymerase chain
      reaction (RT-PCR), the California isolate exhibited an identical restriction
      fragment length polymorphism (RFLP) pattern to some isolates obtained from
      California, known as California 99 isolates. Commercial Mass-Conn and Mass-Ark
      vaccines were used to vaccinate commercial broiler chickens via eye drop once at
      1 or 10 days of age or twice at 1 and 10 days of age. At 27 days of age the birds
      were challenged via eye drop with the isolated IBV California 99 strain.
      Protection was measured by failure to reisolate the challenge virus from tracheas
      5 days postchallenge and complemented withthe tracheal and epithelium thickness
      scores. When the Mass-Ark vaccine was included in the vaccination programs, there
      was protection against challenge with the IBV California 99 isolate. The Mass
      Conn vaccine conferred protection when used once at 1 day of age and twice at 1
      and 10 days of age. However, no total protection was achieved when used as the
      only vaccine at 10 days of age, since one of the replicates was positive for
      virus isolation. Significant differences (P < 0.05) in the epithelium thickness
      and tracheal scores were observed between the unvaccinated-unchallenged group and
      the groups vaccinated once or twice with the Mass-Conn vaccine. Based on these
      results, all chickens were protected against the California 99 isolate when the
      IBV Arkansas type was used as a vaccine.

PMID- 14708976
TI  - Efficacy of DNA vaccines against infectious bursal disease virus in chickens
      enhanced by coadministration with CpG oligodeoxynucleotide.
AB  - The objective of the present study was to investigate the feasibility of a DNA
      vaccine and CpG oligodeoxynucleotide (ODN) to protect chickens against infectious
      bursal disease virus (IBDV) infection. Two plasmids DNA carrying VP2 genes of the
      very virulent (vv) strain of IBDV were constructed with reverse transcription
      polymerase chain reaction and designated as pcDNA3.1-VP2 and pCI-VP2. The VP2
      protein expressed in COS-7 cells transfected with the plasmid was confirmed by
      indirect immunofluorescence assay. Seven-day-old chickens were intramuscularly
      injected with the plasmids alone or plus commercial attenuated infectious bursal
      disease (IBD) vaccine or synthetic CpG ODN twice at weekly intervals. Chickens at
      5 wk old were orally inoculated with vvIBDV strain 99J1 and observed for 7 days
      after challenge. Immunization with plasmid plus commercial attenuated IBD vaccine
      or CpG ODN conferred protection for 70%-80% of chickens, as evidenced by the
      absence of dinical signs, mortality, and atrophy in the cloacal bursa. About 25%
      45% of chickens vaccinated with commercial attenuated IBD vaccine or pcDNA3.1-VP2
      or pCI-VP2 plasmid alone had dinical signs and died after challenge. Furthermore,
      there were significantly different histopathologic lesion scores in the clocal
      bursae between the pcDNA3.1-VP2 or pCI-VP2 plus CpG or live vaccine and pcDNA3.1
      VP2, pCI-VP2, or live vaccine vaccinated group. Enzyme-linked immunosorbent assay
      antibody titers in chickens vaccinated the constructs DNA plus live vaccine or
      CpG ODN were significantly higher than in those inoculated with the constructs or
      the live vaccine alone. These results suggest that coadministration of the
      constructed plasmid pcDNA3.1-VP2 or pCI-VP2 with CpG ODN or commercial attenuated
      IBD vaccine could protect chickens efficiently from direct vvIBDV challenge.

PMID- 14708977
TI  - Intestinal immunomodulation by vitamin A deficiency and lactobacillus-based
      probiotic in Eimeria acervulina-infected broiler chickens.
AB  - In a 2 X 2 factorial study, a broiler starter ration was amended for vitamin A
      (control, C; deficient, A) and probiotic status (-, P) to investigate their
      modulatory effects onthe host immune system. Birds were inoculated orally with
      Eimeria acervulina (EA) oocysts, and disease susceptibility was evaluated by
      assessment of fecal oocyst shedding. Humoral and local cellular mediated immunity
      were assessed by evaluation of antibody and cytokine (interferon-gamma [IFN
      gamma] and interleukin-2 [IL-2]) levels in sera and intestinal secretions on a 3
      day interval after inoculation. Fecal oocyst shedding was highest (P < 0.05) in A
      birds, followed by AP, C-, and CP birds. Feeding the probiotic reduced shed
      oocysts by 20% in A fed birds and by 26% in C fed birds. Intestinal IFN-gamma was
      relatively constant in all treatment groups except for A-, where it declined
      steadily and was lower (P < 0.05) from day 6 on. Serum IFN-gamma levels
      fluctuated within each treatment and over time were not revealing. Intestinal IL
      2 was highest in CP birds at 3 and 9 days postinfection (DPI) and lowest in A-
      birds at 3, 9, and 12 DPI (P < 0.05); no difference between treatments was found
      at 6 DPI (P > 0.05). Eimeria-specific intestinal antibody (Ab) level was constant
      (P > 0.05) in C- birds but increased with time (P < 0.05) in A-, AP, and CP
      birds. Serum Ab levels were also constant in A- and CP birds but increased (P <
      0.05) in C- and AP birds after 6 DPI. The data demonstrate for the first time a
      probiotic-enhanced immunity in vitamin A deficient birds. This study is also the
      first to demonstrate the probiotic effect on local cell-mediated immunity of
      chickens, best manifested by apparent lower intestinal invasion and development
      by EA, on the basis of higher IL-2 secretion and lower EA oocyst production.

PMID- 14708978
TI  - Comparison of Chinese field strains of avian leukosis subgroup J viruses with
      prototype strain HPRS-103 and United States strains.
AB  - Eight Chinese field strains of subgroup J avian leukosis viruses (ALV-J) were
      isolated from broilers or parent stocks during January 1999 to April 2001. One
      strain, SD9902, was an acute transforming virus, able to induce typical
      myelocytomatosis in 22-38 days after inoculation of 1-day-old meat-type chicks.
      The envelope protein and 3'-untranslated region (UTR) of the eight field strains
      were compared with the U.K. prototype HPRS-103 and several U.S. field strains
      isolated in 1993-97. All Chinese strains shared an almost identical deletion with
      the U.S. strain 4817 in the E element region of 3'-UTR when compared with the
      prototype HPRS-103, indicating that they have a very close phylogenic
      relationship. Every year, China has to import grandparent stocks of meat-type
      chickens, mainly from the United States. Chinese isolates should represent a part
      in the phylogenic tree of U.S. ALV-J evolution. Envelope protein gp85 amino acid
      sequence analysis demonstrated that, interestingly, all recent Chinese isolates
      were more closely related to HPRS-103 and the earliest U.S. isolates but not to
      the late U.S. isolates. The result implies that envelope gp85 may not have
      diverged from prototype and older strains. It is also possible that some recently
      imported birds could have been infected by the older viruses that were introduced
      in the late 1990s.

PMID- 14708979
TI  - Antigen-specific lymphocyte proliferation and interleukin production in chickens
      immunized with killed Salmonella enteritidis vaccine or experimental subunit
      vaccines.
AB  - Lymphocyte proliferation and interleukin (IL)-2 and IL-6 levels in serum were
      measured as indicators of cell-mediated immunity after immunization of chickens
      with a commercial killed Salmonella enteritidis (SE) vaccine or experimental
      subunit vaccines of crude protein (CP) extract or the outer membrane protein
      (OMP). Significantly increased proliferative responses to SE flagella, but not
      lipopolysaccharide, porin, CP, or OMP, were observed at 1 wk postimmunizarion in
      the three vaccination groups. The responses to flagella were specific because
      flagella-induced proliferation was not seen in chickens immunized with adjuvant
      alone. Of the three immunization protocols, use of the killed SE vaccine appeared
      most effective because it induced higher flagella-stimulated lymphocyte
      proliferation at 1 and 2 wk postvaccination compared with the CP- and OMP
      vaccinated groups. Significantly increased IL-2 and IL-6 levels in serum were
      seen at 1 wk postimmunization in the three vaccination groups compared with
      adjuvant alone, but there were no differences between the killed vaccine and the
      subunit vaccines at this time, and the levels of both lymphokines returned to
      baseline at 2 wk postimmunization. We conclude that cell-mediated immunity to SE
      after vaccination with the killed bacterial vaccine or subunit vaccines is
      transient and mainly limited to flagella.

PMID- 14708980
TI  - Immunopathologic investigations with an attenuated chicken anemia virus in day
      old chickens.
AB  - The immunopathologic effects induced by two attenuated chicken anemia virus (CAV)
      isolates, known as cloned isolate 34 (CI 34) and cloned revertant isolate 18 (CRI
      18), that were derived from highly passaged pools of Cux-1 CAV isolate, were
      compared with those induced by a pathogenic, molecularly cloned, low-passage Cux
      1 isolate (CI Cux). This comparison involved the intramuscular inoculation of 1
      day-old specific-pathogen-free chicks with each of the viruses and investigation
      of birds at selected days postinoculation for gross pathology and depletions in
      the thymic T-cell populations as determined by flow cytometry. Whereas infection
      with the pathogenic CI Cux produced severe anemia and pronounced bone marrow and
      thymus lesions, infections with the attenuated CRI 18 and CI 34 isolates produced
      no anemia, no or mild lesions, respectively, and moderate T-cell depletion. The
      results suggest that, with CAV, reduced pathogenicity for 1-day-old chicks
      correlates with reduced depletion of T-cell populations in the thymus and with
      reduced severity of lesions in the thymus and bone marrow.

PMID- 14708981
TI  - The effect of dietary lysine deficiency on the immune response to Newcastle
      disease vaccination in chickens.
AB  - The effect of lysine deficiency on chicken immune function was evaluated using
      broiler chickens fed a diet with lysine at 67% of the control diet (1.24%
      lysine). The evaluation of humoral immune function was conducted by measuring the
      antibody production to a live Newcastle disease virus (NDV) vaccination using the
      hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay
      (ELISA). The cellular immune function was evaluated through the use of cutaneous
      basophil hypersensitivity test. The antibody response to NDV vaccination was
      reduced in broiler chickens fed a lysine-deficient diet when measured by ELISA
      but not when measured by HI. The cell-mediated immune response was also reduced
      by lysine deficiency.

PMID- 14708982
TI  - Effect of electrostatic space charge on reduction of airborne transmission of
      Salmonella and other bacteria in broiler breeders in production and their
      progeny.
AB  - Salmonella in birds is a concern because of the human foodborne illness
      associated with the consumption of poultry meat and eggs. One of the methods of
      transmission of Salmonella within a flock can be by the air. Therefore, we used
      reduction of transmission of Salmonella to monitor the effectiveness of the
      electrostatic space charge system (ESCS). During the average broiler breeder
      laying cycle of 40 wk, a large amount of dust becomes airborne and accumulates on
      walls, ceiling, and equipment. Many microorganisms adhere to these dust
      particles, making dust an excellent vector for horizontal disease transmission
      between birds. We used two environmentally controlled rooms containing commercial
      broiler breeders to evaluate the effectiveness of an ESCS that produced a strong
      negative electrostatic charge to reduce airborne dust and, subsequently,
      microorganism levels. The ESCS caused the dust to become negatively charged,
      therefore moving to the grounded floor in the treatment room. The use of the ESCS
      resulted in a significant reduction (P < 0.0001, 61% reduction) in airborne dust
      concentration levels, which resulted in a significant reduction (P < 0.0001, 76%
      reduction) in total airborne bacteria and gram-negative bacteria (48% reduction)
      in the treatment room. Significant reductions (P < 0.05) of gram-negative
      bacteria (63% reduction) on the egg collection belts were also recorded in the
      treatment room, which resulted in a significant reduction (P < 0.0001) of gram
      negative bacteria (28% reduction) on the eggshell surface. The ESCS treatment
      resulted in fewer Salmonella enteritidis-positive hens and their progeny from the
      treatment room due to reductions of dust and airborne bacteria. In addition, this
      significant reduction in bacteria on the eggshell surface should result in less
      bacteria in the day-old chicks, therefore better early chick livability. There
      was no significant difference (P > 0.05) in egg production, male or female body
      weights, mortality, or reproductive performance in the ESCS room compared with
      the control room.

PMID- 14708983
TI  - Influence of a reovirus-antibody complex vaccine on efficacy of Marek's disease
      vaccine administered in ovo.
AB  - Two experiments determined the influence of an experimental reovirus-antibody
      complex vaccine on Mareks disease virus (MDV) vaccine when used in ovo. Designs
      were the same except that specific-pathogen-free (SPF) broiler eggs were used in
      Experiment 1 and commercial broiler eggs with maternal antibodies against
      reovirus were used in Experiment 2. At 18 days of incubation, embryos were
      separated into four groups and inoculated with either diluent, MDV vaccine,
      reovirus-antibody complex vaccine, or a combination of reovirus-antibody complex
      and MDV vaccine. At 5 days of age, half the chickens in each group were
      challenged with MDV. At 7 wk old, all were euthanatized, weighed, and examined.
      At 7 days of age, remaining chickens in each group were challenged with reovirus.
      At 21 days old, chickens were euthanatized and weighed. No vaccine adversely
      affected hatchability or posthatch mortality in SPF or commercial chickens. There
      were no significant differences in protection against reovirus challenge when
      vaccines were used separately or in combination, and lesion scores were nearly
      identical in all vaccinated groups in both experiments. However, percentage of
      protection against reovirus was lower in Experiment 2, indicating an adverse
      effect of maternal immunity on efficacy of the reovirus vaccine. There were no
      significant differences in protection against MDV when the vaccines were used
      separately or combined. Severity of MDV lesions was nearly identical in all
      vaccinated groups in both experiments. However, the combination of vaccines gave
      numerically lower protection against MDV than MDV vaccine alone. Use of a larger
      number of birds, as in field conditions, may result in statistically lower
      protection for the vaccine combination. Large field trials are needed to
      determine the potential of the reovirus-antibody complex vaccine.

PMID- 14708985
TI  - Immunization of turkeys with a DNA vaccine expressing either the F or N gene of
      avian metapneumovirus.
AB  - In this study we compared protection by DNA vaccination with the F (pCMV-F) or N
      (pCMV-N) gene from avian metapneumovirus (aMPV) in turkeys. One-week-old turkey
      poults received two intramuscular injections 2 wk apart. Birds were challenged
      with a turkey-embryo-adapted aMPV at 5 wk of age. Birds vaccinated with pCMV-F
      had decreased clinical signs of disease as well as significantly reduced virus
      load in tracheal swabs compared with birds vaccinated with pCMV-N or unvaccinated
      control birds. Serum neutralizing antibodies were significantly higher in birds
      receiving pCMV-F compared with all other groups. These results indicate that DNA
      vaccination with the F, but not N, gene of aMPV can induce significant protection
      against aMPV infection.

PMID- 14708984
TI  - Individual and combined effects of the Fusarium mycotoxins fumonisin B1 and
      moniliformin in broiler chicks.
AB  - The individual and combined effects of feeding fumonisin B1 (FB1; 0, 100, 200 mg
      FB1/kg) and moniliformin (M; 0, 100, 200 mg M/kg) were evaluated using a 3 x 3
      factorial arrangement of treatments. Significant mortality (P < 0.05) occurred in
      chicks fed all diets containing 200 mg M/kg (50%-65%). Compared with controls and
      chicks fed FB1, both feed intake and body weight gain were decreased (P < 0.05)
      in chicks fed diets containing 100 mg M/kg. Chicks fed M had heavier heart
      weights (P < 0.05) than control chicks or chicks fed FB1. Compared with controls,
      chicks fed diets containing 200 mg M/kg or a combination of 200 mg FB1/kg and 100
      mg M/kg had increased kidney and liver weights (P < 0.05). Significant FB1 by M
      interactions (P < 0.05) were observed for serum total protein and aspartate
      aminotransferase. Mild to moderate periportal extramedullary hematopoiesis and
      mild focal hepatic necrosis were observed in chicks fed FB1 alone. An increased
      incidence of large pleomorphic cardiomyocyte nuclei, loss of cardiomyocytes, and
      mild focal renal tubular mineralization were observed in chicks fed M alone. Both
      cardiac and renal lesions were observed in chicks fed combinations of FB1 and M.
      Data indicate FB1 and M, alone or in combination, can adversely affect chick
      performance and health at these dietary concentrations. The interactive effects
      of FB1 and M were not synergistic and were less than additive in nature. At the
      dietary concentrations studied, M is much more toxic to broilers than FB1.

PMID- 14708986
TI  - Molecular characterization of plasmids with antimicrobial resistant genes in
      avian isolates of Pasteurella multocida.
AB  - The complete nucleotide sequences of two plasmids from avian isolates of
      Pasteurella multocida that caused outbreaks of fowl cholera in Taiwan were
      determined. The entire sequences of the two plasmids, designated as pJR1 and
      pJR2, were 6792 bp and 5252 bp. Sequence analysis showed that the plasmid pJR1
      contained six major genes: the first gene (sulII) encoded a type II sulfonamide
      resistant dihydropteroate synthase, the second gene (tetG) encoded a tetracycline
      resistance protein, the third gene (catB2) encoded a chloramphenicol
      acetyltransferase, the fourth gene (rep) encoded a replication protein, and the
      fifth and sixth genes (mbeCy and deltambeAy) encoded proteins involved in the
      mobilization of plasmid. The plasmid pJR2 contained five major genes: the first
      gene (deltaintI1) encoded a truncated form of a type I integrase, the second gene
      (aadA1) encoded an aminoglycoside adenylyltransferase that confers resistance to
      streptomycin and spectinomycin, the third gene (blaP1) encoded a beta-lactamase
      that confers resistance to ampicillin and carbenicillin, and the fourth and fifth
      genes might encode proteins involved in the plasmid replication or segregation.
      Sequence comparisons showed that the antibiotic resistance genes found in pJR1
      and pJR2 exhibited a high degree of sequence homology to the corresponding genes
      found in a great variety of gram-negative bacteria, including Escherichia coli,
      Salmonella enterica Typhimurium DT104, Psedomonas spp., P. multocida, Mannheimia
      spp., and Actinobacills pleuropneumoniae, which suggests that these resistance
      genes were disseminated in these bacteria. Although sulII and tetG genes were
      found previously in P. multocida or Mannheimia spp., this is the first report on
      the presence of catB2, aadA1, and blaP1 genes in bacteria of the family
      Pasturellaceae. Moreover, the aadA1 and blaP1 genes found in pJR2 were organized
      into an integron structure, which is a site-specific recombination system capable
      of capturing and mobilizing antibiotic resistance genes. This is also the first
      report on the presence of an integron in bacteria of the family Pasteurellaceae.
      The presence of a P. multocida integron might facilitate the spreading of
      antibiotic resistance genes between P. multocida and other gram-negative
      bacteria.

PMID- 14708987
TI  - Pathology and histology of dietary tryptophan deficiency in broiler chicks.
AB  - The purpose of this experiment was to characterize a lesion of the rhamphotheca
      associated with tryptophan (TIRP) deficiency, search for other histological
      abnormalities,and determine whether bird size and housing conditions are
      contributing factors to these lesions. Day-old broiler chicks (Ross X Ross 308)
      were placed in either floor pens with fresh pine shavings or Petersime battery
      brooders with two pens of 10 chicks each per treatment. Broiler chicks from 0 to
      21 days of age were fed adequate (0.24%) and deficient (0.09%) levels of TRP in
      diets based on corn, corn gluten meal, and gelatin. Separate groups of control
      chicks were pair fed daily with the deficient chicks. Deficient chicks grew less
      efficiently than did the pair-fed controls. Upon gross examination, a lesion of
      the maxillary rhamphotheca in the vicinity of the nares was observed in 61% of
      TRP-deficient birds housed in the battery and 13% of the birds housed in floor
      pens. A similar gross lesion was only observed in one control bird. These lesions
      were located along the upper portion of the beak between the nares and appeared
      as a crusty or scab-like area on gross examination, composed of detritus,
      heterophils, and plasma protein. Inflammation occasionally was observed at the
      dermoepidermal junction. The incidence of lesions was reduced in floor pens
      compared to battery brooders, but similarly sized birds did not exhibit the
      lesion. The number of lesions seen grossly and histologically in TRP-deficient
      birds, as compared to control birds, supports the hypothesis that TRP deficiency
      is the primary cause of these lesions around the nares of broilers. Secondary
      environmental factors, perhaps coprophagy, also influence the incidence of the
      lesion.

PMID- 14708988
TI  - Bacteriophage treatment of a severe Escherichia coli respiratory infection in
      broiler chickens.
AB  - A bacteriophage to a serotype 02, nonmotile Escherichia coli was isolated from
      municipal waste treatment facilities and poultry processing plants. A study was
      conducted to determine the efficacy of multiple vs. single intramuscular (i.m.)
      injections of bacteriophage to treat a severe E. coli respiratory infection. The
      birds were challenged at 7 days of age by injection of 6 x 10(4) colony-forming
      units (cfu) of E. coli into the thoracic air sac followed by an i.m. injection
      into the thigh with either heat-killed or active bacteriophage. There were 16
      treatments with three replicate pens of 10 birds. There were four control
      treatments, which included untreated birds, birds injected with either heat
      killed or active bacteriophage, and birds challenged only with E. coli. In the
      remaining treatments, birds were injected with heat-killed or active
      bacteriophage either once immediately after E. coli challenge or immediately
      after challenge and at 8 and 9 days of age, once at 8 days of age or at 8, 9, and
      10 days of age, and once at 9 days of age or at 9, 10, and 11 days of age.
      Mortality was significantly decreased from 57% to 13% in the birds given a single
      i.m. injection of bacteriophage immediately after E. coli challenge, and there
      was complete recovery in birds treated immediately after challenge and at 8 and 9
      days of age, which was a significant improvement from the single injection
      treatment. There was a significant reduction in mortality from 57% to 10% in the
      birds treated with bacteriophage once at 8 days of age and those birds treated at
      8, 9, and 10 days of age, with no difference between single or multiple
      treatments. The mortality in the single or multiple phage treated birds that
      started at 9 days of age was reduced from 57% to 28% and 27%, respectively, but
      was not statistically different from the control. These data suggest that
      bacteriophage can be an effective treatment when administered early in this
      experimental E. coli respiratory disease and that early multiple treatments are
      better than a single treatment. The efficacy of bacteriophage treatment
      diminishes as it is delayed, with no difference between single or multiple
      treatments. Bacteriophage may provide an effective alternative to antibiotics,
      but like and biotic therapy, the effectiveness of phage to rescue animals
      decreases the longer treatment is delayed in the disease process.

PMID- 14708989
TI  - Real-time polymerase chain reaction testing for the detection of Mycobacterium
      genavense and Mycobacterium avium complex species in avian samples.
AB  - Diagnosis of avian mycobacteriosis, caused by Mycobacterium genavense or species
      belonging to the Mycobacterium avium complex (MAC), is problematic. Polymerase
      chain reaction (PCR) offers rapid and sensitive detection of minute quantities of
      DNA, and conventional protocols have been used for evaluating avian specimens.
      The recent development of real-time PCR offers several advantages over
      conventional PCR. In attempts to improve diagnosing avian mycobacteriosis, a real
      time TaqMan PCR assay was developed targeting the 65-kD heat shock protein gene
      of M. genavense and MAC spp. Nineteen reference isolates, 16 clinical isolates,
      and 32 avian tissue samples were used to evaluate the assay. When sufficient
      amplicons were produced, the species of mycobacteria was determined by standard
      sequencing of TaqMan PCR products and compared with results from commercial
      mycobacteriology laboratories and/or standard sequencing of conventional PCR
      products. The TaqMan PCR detected DNA from reference isolates of M. genavense,
      MAC spp., and Mycobacterium tuberculosis complex spp. Of the clinical isolates,
      the TaqMan PCR detected DNA from 10 of 12 Mycobacterium avium avium isolates and
      two of three Mycobacterium avium intracellulare isolates. For the tissue samples,
      the TaqMan PCR amplified DNA in six of nine samples that were identified by
      sequencing of conventional PCR products and/or by commercial mycobacteriology
      laboratories as being MAC spp. positive and three of four samples that were
      positive for M. genavense. There was some disagreement between speciation results
      from the TaqMan PCR and those from commercial mycobacteriology laboratories or
      conventional PCR or both. This disagreement was suspected to be because of
      relatively small numbers of base pairs in the TaqMan PCR products. The TaqMan PCR
      may provide a useful tool for evaluating clinical samples for DNA from
      mycobacteria species that most commonly infect birds; however, further refinement
      is needed in order to improve sensitivity and provide more accurate speciation.

PMID- 14708990
TI  - Experimental selection of virus derivatives with variations in virulence from a
      single low-pathogenicity H6N1 avian influenza virus field isolate.
AB  - A mixture of viruses with variations in virulence is likely present within a low
      pathogenicity avian influenza virus (LPAIV) population. An H6N1 AIV was isolated
      from a field case showing 3.8% weekly mortality and a 33% egg production drop in
      Taiwan. The pathologic lesions included proventricular hemorrhage and urate
      deposition in the kidneys and on visceral organs. From the field isolate, a done
      (2838N) that caused no lesions or death was obtained using limit dilution in
      chicken embryos and a done (2838V) that caused renal lesions and death was
      obtained using contact infection in chicks. Both clones were inoculated
      intranasally in 4-week-old specific pathogen free (SPF) chickens to test their
      virulence. Renal urate deposition was found in chickens inoculated with 2838V but
      not in chickens inoculated with 2838N. In situ hybridization, polymerase chain
      reaction, and virus isolation were used to confirm the spread of 2838V from the
      respiratory tract to the renal tissue. We found that contact infection in
      chickens is a good method to obtain a more virulent done from a heterogeneous
      virus population.

PMID- 14708991
TI  - Safety and efficacy of an experimental reovirus vaccine for in ovo
      administration.
AB  - A commercial reovirus vaccine alone or experimental reovirus vaccine plus
      antibody complex were inoculated into 18-day-old specific pathogen free (SPF)
      broiler embryos at 0.1 of the recommended chick dose. The following groups were
      used: group 1A was not vaccinated or challenged; group 1B was not vaccinated, but
      was challenged with virulent reovirus; group 2 received the vaccine complexed
      with 1/4 dilution of antiserum; group 3 received the vaccine with 1/8 dilution of
      antiserum; group 4 received the vaccine with 1/16 dilution of antiserum, and
      group 5 received vaccine alone. At 1, 3, 6, 9, and 12 days of age, serum was
      collected and antibody against avian reovirus was analyzed by enzyme-linked
      immunosorbent assay (ELISA). At the same times, spleens were collected and
      vaccine virus detected by inoculating chicken embryo fibroblasts (CEFs) and
      examining for cytopathic effect. At 15 days of age, chickens in groups 2-5 were
      challenged with reovirus. At 22 days of age, birds were euthanatized and weighed.
      Efficacy of the vaccines was based on safety, percent protection, and antibody
      response. In ovo vaccination with the commercial or experimental vaccines did not
      adversely affect hatchability of SPF chickens. The vaccine complexed with
      antibody resulted in significantly less posthatch mortality (3.7%) when compared
      to mortality of chickens that received vaccine alone (17%). Both vaccine virus
      recovery and antibody response were delayed at least 3 days in birds receiving
      the experimental vaccines. In evo administration of reovirus antibody complex
      vaccines provided at least 70% protection. The experimental reovirus-antibody
      complex vaccines were safe and efficacious when given in ovo to SPF broiler
      embryos.

PMID- 14708992
TI  - Cecal colonization of chicks by bovine-derived strains of Campylobacter.
AB  - Campylobacter jejuni and Campylobacter coli strains were isolated from feces of
      dairy cattle at farms with no known problem due to campylobacteria. Farms were
      located in the northeast, desert southwest, and Pacific west. Twenty isolates
      were identified by ribotyping with a RiboPrinter. The ability of these bovine
      isolates to colonize the ceca of chicks was determined by challenge inoculation
      and reisolation of the challenge strain from the ceca at 1 and 2 wk after
      challenge. Isolates recovered from chick ceca were examined by ribotyping to
      assure they matched the challenge strain. One hundred percent of the bovine
      derived challenge strains were capable of colonizing chicks. These results
      indicate that dairy cattle may be asymptomatic Campylobacter carriers and
      potential sources of campylobacteria contamination of poultry facilities.

PMID- 14708993
TI  - An adenovirus linked to mortality and disease in long-tailed ducks (Clangula
      hyemalis) in Alaska.
AB  - An adenovirus was isolated from intestinal samples of two long-tailed ducks
      (Clangula hyemalis) collected during a die-off in the Beaufort Sea off the north
      coast of Alaska in 2000. The virus was not neutralized by reference antiserum
      against known group I, II, or III avian adenoviruses and may represent a new
      serotype. The prevalence of the virus was determined in live-trapped long-tailed
      ducks at the mortality site and at a reference site 100 km away where no
      mortality was observed. Prevalence of adenovirus antibodies in serum samples at
      the mortality site was 86% compared to 10% at the reference site. Furthermore,
      50% of cloacal swabs collected at the mortality site and only 7% of swabs from
      the reference site were positive for adenoviruses. In 2001, no mortality was
      observed at either of the study areas, and virus prevalence in both serum and
      cloacal samples was low, providing further evidence that the adenovirus was
      linked to the mortality event in 2000. The virus was used to infect long-tailed
      ducks under experimental conditions and resulted in lesions previously described
      for avian adenovirus infections and similar to those observed in long-tailed duck
      carcasses from the Beaufort Sea. The status of long-tailed ducks has recently
      become a concern in Alaska due to precipitous declines in breeding populations
      there since the mid-1970s. Our findings suggest that the newly isolated
      adenovirus is a disease agent and source of mortality in long-tailed ducks, and
      thus could be a contributing factor in population declines.

PMID- 14708994
TI  - Characterizing avian Escherichia coli isolates with multiplex polymerase chain
      reaction.
AB  - Colibacillosis caused by Escherichia coli infections account for significant
      morbidity and mortality in the poultry industry. Yet, despite the importance of
      colibacillosis, much about the virulence mechanisms employed by avian E. coli
      remains unknown. In recent years several genes have been linked to avian E. coli
      virulence, many of which reside on a large transmissible plasmid. In the present
      study, a multiplex polymerase chain reaction (PCR) protocol to detect the
      presence of four of these genes is described. Such a protocol may supplement
      current diagnostic schemes and provide a rapid means of characterizing the E.
      coli causing disease in poultry. The targets of this procedure included iss, the
      increased serum survival gene; tsh, the temperature sensitive hemagglutinin gene;
      cvi, the ColV immunity gene; and iucC, a gene of the aerobactin operon.
      Organisms, known for their possession or lack of these genes, were used as a
      source of the template DNA to develop the multiplex PCR protocol. Identity of the
      amplicons was confirmed by size, DNA:DNA hybridization with specific gene probes,
      and DNA sequencing. When the multiplex PCR protocol was used to characterize 10
      E. coli isolates incriminated in avian colibacillosis and 10 from the feces of
      apparently healthy birds, nine of the isolates from apparently healthy birds
      contained no more than one gene, while the 10th contained all four. Also, eight
      of the isolates incriminated in colibacillosis contained three or more genes,
      while the remaining two contained two of the target genes. Interestingly, the
      isolates of sick birds containing only two of the targeted genes killed the least
      number of embryos,and the isolate of healthy birds that contained all the genes
      killed the most embryos amongthis group. These genes were not found among the non
      E. coli isolates tested, demonstrating the procedure's specificity for E. coli.
      Overall, these results suggest that this protocol might be useful in
      characterization and study of avian E. coli.

PMID- 14708995
TI  - Effect of a commerical competitive exclusion product on the colonization of
      Salmonella infantis in day-old pheasant chicks.
AB  - One-day-of-age pheasant chicks were treated orally with the competitive exclusion
      product Broilact in three replicate trials. The following day the treated chicks
      and untreated control chicks were challenged likewise with approximately 10(3)
      colony-forming units (cfu) of Salmonella infantis. Five days after challenge the
      cecal contents of the birds were examined quantitatively and by enrichment for S.
      infantis. In all three trials Broilact effectively reduced colonization of the
      challenge organism, the mean infection factor (IF) value (the logarithmic number
      of colony forming units of salmonella organisms per gram of cecal contents) for
      the treated groups being 2.9 and that for the salmonella control groups 8.4.
      Mortality during the 1 week rearing period was 5.0% in the Broilact treated
      groups and 8.5% in the salmonella control groups.

PMID- 14708996
TI  - Characterization of Egyptian field strains of infectious bursal disease virus.
AB  - The reverse transcriptase-polymerase chain reaction/restriction fragment length
      polymorphism (RT-PCR/RFLP) technique was used for identification and
      characterization of Egyptian field strains of infectious bursal disease viruses
      (IBDVs) that caused severe outbreaks with (30%-60%) mortality rate. Twenty-four
      bursal samples collected from 24 field outbreaks in commercially reared chicken
      flocks experiencing signs typical of infectious bursal disease (IBD) were used.
      Ten of the bursal samples examined were determined to contain IBDV as evidenced
      by amplification of a 743-bp region of the VP2 gene of IBDV by RT-PCR. The RT-PCR
      products of the detected viruses were characterized by digestion with three
      restriction enzymes, BstN, MboI, and SpI. Three different RT-PCR/RFLP profiles
      were observed. Seven of the detected viruses had RFLP profiles identical to the
      very virulent European strains of IBDV (vvIBDVs). One virus had a RFLP profile
      identical to the U.S. classic vaccine strain, and one virus had a unique RFLP
      profile. The clinical history of the outbreaks and the presence of the SspI site
      in the 743-bp RT-PCR fragment were the criteria for designating the viruses as
      belonging to the very virulent (vv) phenotype.

PMID- 14708997
TI  - Titration of Marek's disease cell-associated vaccine virus (CVI 988) of
      reconstituted vaccine and vaccine ampoules from Dutch hatcheries.
AB  - Thirty-one outbreaks of Marek's disease (MD) were reported in the Netherlands and
      retrospectively analyzed. The outbreaks occurred mostly in vaccinated commercial
      layer and a few breeder flocks of several breeds; however, the cause of the
      outbreaks could not be established. Therefore, in a prospective study, the
      occurrence of true vaccine failures was assessed onfive hatcheries. The plaque
      forming units (PFU) of MD vaccine per chicken dose were determined through in
      vitro assays on vacine ampoules (2 to 5 per hatchery) and samples of
      reconstituted vaccine (approximately 22 per hatchery). All forty reconstituted
      vaccine samples of hatcheries 1 and 4 showed PFU doses <10(3). In hatchery 4, 14
      samples showed extreme low PFU (< or = 10 PFU). In hatcheries 2, 3, and 5, the
      numbers of MD vaccine suspensions with a titer > or = 10(3) PFU, which is the
      standard required, were 1 (5%), 17 (77%), and 3 (14%), respectively. Some vaccine
      ampoules showed < 10(3) PFU per chicken dose. This study shows the usefulness to
      assess the PFU per chicken dose of reconstituted MD vaccine and vaccine ampoules
      to unravel true vaccine failures, which could result in disease outbreaks in the
      field.

PMID- 14708998
TI  - Chicken anemia virus in broilers: dynamics of the infection in two commercial
      broiler flocks.
AB  - Chicken anemia virus (CAV) can cause a disease syndrome characterized by severe
      anemia, bone marrow atrophy, and severe immunosuppression in young chicks.
      Maternal antibodies prevent these clinical signs but do not prevent infection,
      transmission of the virus, or immunosuppression. The clinical disease is rare
      today because of the widespread practice of vaccinating breeders, but the
      subclinical form of the disease is ubiquitous. The dynamics of CAV infection, CAV
      antibody responses, relative lymphoid organ weights, and associated lesions were
      studied in two broiler flocks from a commercial producer. Both groups had
      detectable CAV antibodies at hatch, which waned over the first 3 wk of life. Both
      groups had detectable CAV DNA in both thymi and bursae over the same period. At
      35 days of age, virus was detectable by polymerase chain reaction in 16 of 20
      chickens, and 7 of 20 had detectable antibodies. By 42 days of age, virus was
      detectable in 18 of 20 chickens, and 18 of 20 had antibodies to CAV. We observed
      a decrease in relative thymic weights beginning at 35 days of age, coincidental
      withthe detection of CAV in the thymus. Bursal sizes began to decrease at 28 days
      of age, coincidental with a rise in antibody titers to infectious bursal disease
      virus. In this study, we demonstrated that under typical field conditions CAV
      infections in broilers have unique dynamics unlike those reported in egg laying
      strains of chickens managed under specific-pathogen-free conditions.

PMID- 14708999
TI  - Infection models for Salmonella typhimurium DT110 in day-old and 14-day-old
      broiler chickens kept in isolators.
AB  - A series of experiments was undertaken to investigate the infection dynamics of
      various doses of S. typhimurium in day-old and 14-day-old broiler chickens kept
      in isolators. The infections were followed quantitatively in ceca and ileum by
      enumerating the colony forming units (cfu) of the challenge strain. It was found
      that the inoculation of 10(7) cfu of S. typhimurium to day-old chickens
      established stable cecal infection in all the animals for 35 days. For 14-day-old
      chickens, stable and lasting infections were seen with inoculation of 10(9) cfu.
      Lower doses yielded more variable results, and the bacteria were rapidly
      eliminated from most birds, especially in 14-day-old inoculated chickens.
      Salmonella was found in spleen and liver 2-3 days postinoculation. Salmonella was
      cleared from both organs or reduced to very low numbers within 3 weeks.

PMID- 14709000
TI  - Enteric helminths of juvenile and adult wild turkeys (Meleagris gallopavo) in
      eastern Kansas.
AB  - Viscera of 49 wild turkeys (Meleagris gallopavo) collected in the spring of 2001
      and 23 wild turkeys collected in the fall and winter of 2001-02 from 12 counties
      in eastern Kansas were examined for enteric helminths. Four cestode species, two
      trematode species, one nematode species, and one acanthocephalan species were
      identified. Two cestode and two trematode species present in the spring sample
      also were present in the fall and winter sample. Parasite prevalence was similar
      to previous studies of enteric helminths of wild turkeys except for the low
      numbers of nematode species and individuals recovered in the present study.

PMID- 14709001
TI  - Comparison of four rapid DNA extraction techniques for conventional polymerase
      chain reaction testing of three Mycobacterium spp. that affect birds.
AB  - Mycobacteriosis is an avian disease that is most commonly caused by Mycobacterium
      avium or Mycobacterium genavense. In order to optimize molecular laboratory tests
      for diagnosing mycobacteriosis in birds, we compared four methods of rapid DNA
      extraction with isolates of M. avium, M. genavense, and Mycobacterium fortuitum.
      DNA extraction methods included enzymatic lysis, boiling for 30 min followed by
      enzymatic lysis, four cycles of freezing and thawing followed by enzymatic lysis,
      and bead beating followed by enzymatic lysis. The DNA yield and purity for the
      four methods were evaluated by spectrophotometry and compared. The bead beating
      with enzymatic lysis technique yielded significantly purer and higher
      concentrations of extracted DNA compared with other DNA extraction methods. All
      four methods yielded extraction products for all three organisms that were
      successfully amplified by polymerase chain reaction (PCR) for a fragment in the
      65-kD heat shock protein gene. Subjectively, the PCR amplification products were
      most abundant for samples extracted by bead beating with enzymatic lysis.

PMID- 14709002
TI  - Outbreak of Fowl cholera in Baikal teals in Korea.
AB  - Fowl cholera (FC) caused by Pasteurella multocida was diagnosed in waterfowl,
      Baikal teals (Anas formosa), submitted to the National Veterinary Research and
      Quarantine in Korea. The total number of mortalities was 13,228 out of
      approximately 100,000 birds that wintered in Cheonsoo Bay, the most important
      habitat area of Baikal teals in the world. Clinical signs were detected in only a
      few birds because of sudden death. Grossly, the dead Baikal teals had lesions
      consistent with FC, including multifocal necrotic foci in the liver with
      enlargement, petechial or ecchymotic hemorrhages on the heart, and mucoid
      exudates in the duodenal mucosa. Microscopically, there were hepatocytic necrosis
      with bacterial colonization, hemorrhage and necrosis in the myocardium, and
      hemorrhagic enteritis. Pasteurella multocida was isolated from the liver and the
      heart of all birds examined, and the isolate (P-627) was the serotype 1 X 12 X 13
      by the agar gel immunodiffusion test. In order to estimate the virulence of P
      627, 5-wk-old commercial ducks were exposed intramuscularly or intratracheally to
      the bacterium. On the basis of mortality rate, the isolate, P-627, was found to
      be highly virulent. This is the first report of an outbreak of FC in Baikal teals
      in Korea.

PMID- 14709004
TI  - Reflections and challenges.

PMID- 14709003
TI  - Pathology of listerial encephalitis in chickens in Japan.
AB  - Neural signs (torticollis, drowsiness) and mortality were observed in five
      chickens of a native chicken flock (reared for meat) that included 450 male birds
      on a farm that had 2300 native chickens and 1120 layers. Histologic lesions were
      observed in the medulla oblongata, optic lobe, cerebellum, and spinal cord of the
      affected birds. The lesions, which were most severe in the medulla oblongata,
      were massive abscesses with rarefaction (demyelination and malacia) of the
      parenchyma with gram-positive bacteria. The degenerative and necrotic areas were
      characterized by fibrin thrombosis, hemorrhages, and congestion in the blood
      vessels. Immunohistochemically, the bacteria positive for L. monocytogenes
      antigen were observed in the medulla oblongata, cerebellum, and spinal cord.
      Ultrastructurally, the small rod-shaped and thin-cell-walled bacteria were
      observed in the parenchyma of the medulla oblongata. Listeria monocytogenes
      (serotype 4b) was isolated from the medulla oblongata and spinal cord. The
      pathogenesis of listerial encephalitis in chickens was discussed.

PMID- 14709005
TI  - Improved HPLC determination of phenolic compounds in cv. golden delicious apples
      using a monolithic column.
AB  - A rapid HPLC-DAD determination of phenols in apple using an RP monolithic column
      is reported. Because of the hydrodynamic advantages offered by this kind of
      column and the use of acidified acetonitrile as eluent, assays of apple extracts
      can be performed in <21 min. Assays of pulp and peel extracts were carried out
      without the need for time-consuming sample pretreatment except filtration.
      Several flavanols, hydroxycinnamic acids, dihydrochalcones, and six quercetin
      glycosides were identified and quantified. A seventh quercetin derivative, two
      chalcone-related compounds, and three hydroxycinnamic derivatives were also
      found. Peels proved to be richer in phenols than pulps, the former being composed
      mainly of (-)-epicatechin, procyanidin B2, chlorogenic acid, phloridzin, hyperin,
      and avicularin. In pulps, where the chlorogenic acid was the principal phenolic
      compound, quercetin glycosides were found in very low amounts.

PMID- 14709006
TI  - Development of a new method, based on a bioreactor coupled with an L-lactate
      biosensor, toward the determination of a nonspecific inhibition of L-lactic acid
      production during milk fermentation.
AB  - The development and characteristics of a bioreactor employing bacteria
      (Streptococcus thermophilus) encapsulated in Ca-alginate beads coupled with an L
      lactate biosensor are reported. The biosensor comprises a carbon paste electrode
      modified with enzymes HRP (horseradish peroxidase), LOD (lactate oxidase), and
      FcH (ferrocene) as redox mediator. The measurement of L-lactate is based on the
      signal produced by H(2)O(2), the product of the enzymatic oxidation of L-lactate
      by LOD. The detection of H(2)O(2) is performed at the electrode surface via
      HRP/FcH at low operating potential (-100mV vs Ag/AgCl). Optimization studies were
      performed using the bioreactor in conjunction with an L-lactate electrode
      operating in a flow injection system to assess the ability of encapsulated
      bacteria to ferment carbohydrate solutions. The possibility of using the
      developed method to assess the fermentation capability of milk samples was
      evaluated. Bronopol (2-bromo-2-nitro propane-1,3-diol) was chosen to simulate the
      effect of an inhibitory agent of milk fermentation. The obtained results
      indicated that the evaluation of the amount of L-lactate amount produced through
      the bioreactor could be used as a measure of inhibition of lactic acid production
      in milk samples.

PMID- 14709007
TI  - Characterization of royal jelly proteins in both Africanized and European
      honeybees (Apis mellifera) by two-dimensional gel electrophoresis.
AB  - In this study, the proteins contained in royal jelly (RJ) produced by Africanized
      honeybees and European honeybees (Apis mellifera) haven been analyzed in detail
      and compared using two-dimensional gel electrophoresis, and the N-terminal amino
      acid sequence of each spot has been determined. Most spots were assigned to major
      royal jelly proteins (MRJPs). Remarkable differences were found in the
      heterogeneity of the MRJPs, in particular MRJP3, in terms of molecular weights
      and isoelectric points between the two species of RJ. Furthermore, during the
      determination of the N-terminal amino acid sequence of each spot, for the first
      time, MRJP4 protein has been identified, the existence of which had been only
      implied by cloning of its cDNA sequence. The presence of heterogeneous bands of
      glucose oxidase was also identified. Thus, the results suggest that two
      dimensional gel electrophoresis provides a suitable method for the qualitative
      analysis of the proteins contained in RJ derived from different honeybee species.

PMID- 14709008
TI  - A new test method for the evaluation of total antioxidant activity of herbal
      products.
AB  - A new test method for measuring the antioxidant power of herbal products, based
      on solid-phase spectrophotometry using tetrabenzo-[b,f,j,n][1,5,9,13]
      tetraazacyclohexadecine-Cu(II) complex immobilized on silica gel, is proposed.
      The absorbance of the modified sorbent (lambda(max) = 712 nm) increases
      proportionally to the total antioxidant activity of the sample solution. The
      method represents an attractive alternative to the mostly used radical scavenging
      capacity assays, because they generally require complex long-lasting stages to be
      carried out. The proposed test method is simple ("drop and measure" procedure is
      applied), rapid (10 min/sample), requires only the monitoring of time and
      absorbance, and provides good statistical parameters (s(r)<or= 0.2). The method
      was approved in the analysis of the most popular herbal beverages (black and
      green teas) and drugs (Echinacea products). The results obtained were compared
      with the content of total flavonoids and tannins of teas and total caffeic acid
      derivatives of Echinacea, determined spectrophotometrically.

PMID- 14709009
TI  - Optimization of a supercritical fluid extraction/reaction methodology for the
      analysis of castor oil using experimental design.
AB  - The aim of this work was to optimize a supercritical fluid extraction
      (SFE)/enzymatic reaction process for the determination of the fatty acid
      composition of castor seeds. A lipase from Candida antarctica (Novozyme 435) was
      used to catalyze the methanolysis reaction in supercritical carbon dioxide (SC
      CO(2)). A Box-Behnken statistical design was used to evaluate effects of various
      values of pressure (200-400 bar), temperature (40-80 degrees C), methanol
      concentration (1-5 vol %), and water concentration (0.02-0.18 vol %) on the yield
      of methylated castor oil. Response surfaces were plotted, and these together with
      results from some additional experiments produced optimal extraction/reaction
      conditions for SC-CO(2) at 300 bar and 80 degrees C, with 7 vol % methanol and
      0.02 vol % water. These conditions were used for the determination of the castor
      oil content expressed as fatty acid methyl esters (FAMEs) in castor seeds. The
      results obtained were similar to those obtained using conventional methodology
      based on solvent extraction followed by chemical transmethylation. It was
      concluded that the methodology developed could be used for the determination of
      castor oil content as well as composition of individual FAMEs in castor seeds.

PMID- 14709010
TI  - Initial study of honey adulteration by sugar solutions using midinfrared (MIR)
      spectroscopy and chemometrics.
AB  - Fourier transform infrared (FTIR) spectroscopy and attenuated total reflection
      (ATR) sampling have been used to detect adulteration of honey samples. The sample
      set comprised 320 spectra of authentic (n = 99) and adulterated (n = 221) honeys.
      Adulterants used were solutions containing both d-fructose and d-glucose prepared
      in the following respective weight ratios: 0.7:1.0, 1.2:1.0 (typical of honey
      composition), and 2.3:1.0. Each adulterant solution was added to individual
      honeys at levels of 7, 14, and 21% w/w. Spectral data were compressed and
      analyzed using k-nearest neighbors (kNN) and partial least squares (PLS)
      regression techniques. A number of data pretreatments were explored. Best
      classification models were achieved with PLS regression on first derivative
      spectra giving an overall correct classification rate of 93%, with 99% of samples
      adulterated at levels of 14% w/w or greater correctly identified. This method
      shows promise as a rapid screening technique for detection of this type of honey
      adulteration.

PMID- 14709011
TI  - Engineering of a broad specificity antibody for simultaneous detection of 13
      sulfonamides at the maximum residue level.
AB  - Sulfa antibiotics (sulfonamides) are a group of molecules sharing the p
      aminobenzenesulfonamide moiety. Sulfonamides are used in veterinary and human
      medicine. Sometimes, the meat or milk of medicated animals is contaminated with
      residual sulfonamides. Current analytical methods for sulfonamides are unfit for
      screening of food, because they are either too laborious, insensitive, or
      specific for a few sulfa compounds only. A rapid immunoassay for detection of all
      sulfas in a single reaction would thus be useful. Previously, we used protein
      engineering to improve the broad specificity of sulfa antibody 27G3. In this
      study, we improved the best mutant of the previous studies with site-directed
      mutagenesis. The new mutants recognized different sulfonamides with affinities
      sufficient for detection of all 13 tested sulfonamides below the MRL level. We
      furthermore demonstrated the functionality of one mutant in some real sample
      matrices.

PMID- 14709012
TI  - Extending applicability of the oxygen radical absorbance capacity (ORAC
      fluorescein) assay.
AB  - The ORAC-fluorescein (ORAC-FL) method recently validated using automatic liquid
      handling systems has now been adapted to manual handling and using a conventional
      fluorescence microplate reader. As calculated for Trolox, the precision of the
      method was <3.0, expressed as percent coefficient of variation. The accuracy of
      the method was <2.3, expressed as percent variation of the mean. The detection
      and quantification limits were those corresponding to 0.5- and 1-microM Trolox
      standard solutions, respectively. The method has been applied to 10 pure
      compounds (benzoic and cinnamic acids and aldehydes, flavonoids, and butylated
      hydroxyanisole), to 30 white, rose, and bottled- and oak-aged red wines, and to 7
      commercial dietary antioxidant supplements. All samples exhibited a good linear
      response with concentration. As seen by other methodologies, the chemical
      structure of a compound determines its antioxidant activity (ORAC-FL value). Of
      particular interest were the results with oak-aged red wines from different
      vintages (1989-2002) that confirm influence of vintage, but not origin of the
      oak, in the antioxidant activity of wines from the same variety. Dietary
      antioxidant supplements presented a great variability (170-fold difference) in
      their antioxidant potency. This work proves applicability of the ORAC-FL assay in
      evaluating the antioxidant activity of diverse food samples.

PMID- 14709013
TI  - Mechanisms of cancer chemoprevention by hop bitter acids (beer aroma) through
      induction of apoptosis mediated by Fas and caspase cascades.
AB  - The bitter acids of hops (Humulus lupulus L.) mainly consist of alpha-acids, beta
      acids, and their oxidation products that contribute the unique aroma of the beer
      beverage. Hop bitter acids displayed a strong growth inhibitory effect against
      human leukemia HL-60 cells, with an estimated IC(50) value of 8.67 microg/mL, but
      were less effective against human histolytic lymphoma U937 cells. Induction of
      apoptosis was confirmed in HL-60 cells by DNA fragmentation and the appearance of
      a sub-G1 DNA peak, which were preceded by dissipation of mitochondrial membrane
      potential, cytochrome c release, and subsequent induction of pro-caspase-9 and -3
      processing. Cleavages of PARP and DFF-45 were accompanied with activation of
      caspase-9 and -3 triggered by hop bitter acids in HL-60 cells. The change in the
      expression of Bcl-2, Bcl-X(L), and Bax in response to hop bitter acids was
      studied, and the Bcl-2 protein level slightly decreased; however, the Bcl-X(L)
      protein level was obviously decreased, whereas the Bax protein level was
      dramatically increased, indicating that the control of Bcl-2 family proteins by
      hop bitter acids might participate in the disruption of mitochondrial integrity.
      In addition, the results showed that hop bitter acids promoted the up-regulation
      of Fas and FasL prior to the processing and activation of pro-caspase-8 and
      cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in hop
      bitter acids-induced cells. Taken together, these findings suggest that a certain
      intimate link might exist between receptor- and mitochondria-mediated death
      signalings that committed to cell death induced by hop bitter acids. The
      induction of apoptosis by hop bitter acids may offer a pivotal mechanism for
      their chemopreventive action.

PMID- 14709014
TI  - Isolation and characterization of polyphenol type-A polymers from cinnamon with
      insulin-like biological activity.
AB  - The causes and control of type 2 diabetes mellitus are not clear, but there is
      strong evidence that dietary factors are involved in its regulation and
      prevention. We have shown that extracts from cinnamon enhance the activity of
      insulin. The objective of this study was to isolate and characterize insulin
      enhancing complexes from cinnamon that may be involved in the alleviation or
      possible prevention and control of glucose intolerance and diabetes. Water
      soluble polyphenol polymers from cinnamon that increase insulin-dependent in
      vitro glucose metabolism roughly 20-fold and display antioxidant activity were
      isolated and characterized by nuclear magnetic resonance and mass spectroscopy.
      The polymers were composed of monomeric units with a molecular mass of 288. Two
      trimers with a molecular mass of 864 and a tetramer with a mass of 1152 were
      isolated. Their protonated molecular masses indicated that they are A type doubly
      linked procyanidin oligomers of the catechins and/or epicatechins. These
      polyphenolic polymers found in cinnamon may function as antioxidants, potentiate
      insulin action, and may be beneficial in the control of glucose intolerance and
      diabetes.

PMID- 14709015
TI  - Contribution of conjugated linoleic acid to the suppression of inflammatory
      responses through the regulation of the NF-kappaB pathway.
AB  - Data from a number of researchers have shown that conjugated linoleic acid (CLA)
      has some beneficial health activities in animal models. Because inflammatory
      responses are associated with pathophysiology of many diseases, the aim of this
      study is to explore the effect and mechanism of CLA in the regulation of
      lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages.
      The addition of increasing levels of CLA proportionally augmented the
      incorporation of CLA in cultures. CLA diminished LPS-induced mRNA and protein
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)
      as well as subsequent production of nitric oxide and prostaglandin E(2),
      respectively. We further examined the effect of CLA on LPS-induced NF-kappaB
      activation by Western blot and the electrophoretic mobility shift assay. The
      addition of CLA at 200 microM significantly diminished LPS-induced protein
      expression of the cytoplasmic phosphorylated inhibitor kappaBalpha and nuclear
      p65 as well as NF-kappaB nuclear protein-DNA binding affinity. In conclusion, our
      data suggest that CLA may inhibit LPS-induced inflammatory events in RAW 264.7
      macrophages and this inhibitory activity of CLA, at least in part, occurs through
      CLA modulating the NF-kappaB activation and therefore negatively regulating
      expression of inflammatory mediators.

PMID- 14709016
TI  - Mechanical and water barrier properties of glutenin films influenced by storage
      time.
AB  - The goal of this work was to study the effect of storage time on the functional
      properties of glutenin films plasticized with selected hydrophilic low molecular
      weight compounds: glycerol (GL), triethanolamine (TEA), and sorbitol (S).
      Glutenins were extracted from wheat gluten, and films were cast from film-forming
      solutions. The glutenin-based films were homogeneous, flexible, translucent, and
      easy to handle. Films were stored in an environmental chamber at 50 +/- 5%
      realtive humidity and 23 +/- 2 degrees C. Optical, mechanical, and water vapor
      permeability properties were monitored at regular intervals for 16 weeks. Films
      plasticized with GL and TEA had similar mechanical and water vapor barrier
      properties during the first few days of fabrication. Films plasticized with S
      were stronger, with better water vapor barrier properties. Mechanical and water
      vapor permeability properties of films plasticized with GL changed dramatically
      over time, whereas the properties of films plasticized with TEA and S remained
      stable during storage. Color properties of films plasticized with GL, TEA, and S
      did not change within the time period studied.

PMID- 14709017
TI  - Usefulness of amino acid composition to discriminate between honeydew and floral
      honeys. Application to honeys from a small geographic area.
AB  - With the aim of finding methods that could constitute a solid alternative to
      melissopalynological and physicochemical analyses to determine the botanical
      origin (floral or honeydew) of honeys, the free amino acid content of 46 honey
      samples has been determined. The honeys were collected in a small geographic area
      of approximately 2000 km(2) in central Spain. Twenty-seven honey samples were
      classified as floral and 19 as honeydew according to their palynological and
      physicochemical analyses. The resulting data have been subjected to different
      multivariant analysis techniques. One hundred percent of honey samples have been
      correctly classified into either the floral or the honeydew groups, according to
      their content in glutamic acid and tryptophan. It is concluded that free amino
      acids are good indicators of the botanical origin of honeys, saving time compared
      with more tedious analyses.

PMID- 14709018
TI  - Nutrients and antioxidant molecules in yellow plums (Prunus domestica L.) from
      conventional and organic productions: a comparative study.
AB  - Yellow plums (Prunus domestica L) conventionally and organically grown in the
      same farm were selected to study the influence of different agronomic practices
      on antioxidant vitamins (ascorbic acid, vitamin E, beta-carotene) and phenolics
      (total polyphenols, phenolic acids, flavonols) concentration. Conventional plums
      were grown on tilled soil. Three organic cultivations were performed: tilled
      soil, soil covered with trifolium, and soil covered with natural meadow.
      Differences in macronutrients were marginal, whereas antioxidant vitamins and
      phenolic compounds concentration markedly differed among cultivations. Ascorbic
      acid, alpha-, gamma-tocopherols, and beta-carotene were higher in organic plums
      grown on soil covered with natural meadow. The highest phenolic acids content was
      detected in plums grown on soil covered with trifolium. Total polyphenols content
      was higher in conventional plums. Quercetin was higher in conventional plums, but
      myrecitin and kaempferol were higher in organic plums. Under the same cultivar
      and climate conditions, the type of soil management turned out of primary
      importance in influencing the concentration of health-promoting compounds.

PMID- 14709019
TI  - Cartap hydrolysis relative to its action at the insect nicotinic channel.
AB  - The insecticide cartap is the bis(thiocarbamate) derivative of 2
      (dimethylamino)propane-1,3-dithiol, which on oxidation forms the natural toxicant
      nereistoxin (NTX) [4-(dimethylamino)-1,2-dithiolane]. Both cartap and NTX are ion
      channel blockers of the nicotinic acetylcholine receptor (nAChR). Cartap was
      originally proposed to act only after metabolic conversion to NTX and later
      suggested to block directly without activation. The present study uses a new
      approach to differentiate these hypotheses, that is, pH effects on channel
      blocking activity and hydrolysis rates. As controls, mecamylamine (the classic
      channel blocker) and NTX are stable and similar in channel-blocking potency
      ([(3)H]thienylcyclohexylpiperidine binding assay, honeybee nAChR) at pH 6.1-8.4.
      In contrast, cartap is >200-fold more effective at pH 7.4 than at pH 6.1,
      indicating that it undergoes hydrolytic activation. Cartap slowly hydrolyzes to
      cartap monothiol at pH 6.1 but quickly forms the dithiol and some NTX at pH 7.4.
      The relationship between potency and hydrolysis products at various pH ranges
      suggests that cartap dithiol is the most plausible blocking agent.

PMID- 14709021
TI  - Microwave-assisted extraction for the simultaneous determination of thiamethoxam,
      imidacloprid, and carbendazim residues in fresh and cooked vegetable samples.
AB  - Microwave-assisted extraction (MAE) was carried out for the simultaneous
      determination of the insecticides thiamethoxam [(EZ)-3-(2-chloro-1,3-thiazol-5
      ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine], imidacloprid [1-(6
      chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine], and the fungicide
      carbendazim (methyl benzimidazol-2-ylcarbamate) in vegetable samples. Five crop
      samples consisting of cabbage, tomatoes, chilies, potatoes, and peppers were
      fortified with the three pesticides and subjected to MAE followed by cleanup to
      remove coextractives prior to analysis by high-performance liquid chromatography.
      Using the selected microwave exposure time and power setting, the recoveries of
      the three pesticides from the fortified vegetable samples ranged from 68.1 to
      106%. The corresponding recoveries for samples processed simultaneously but
      without microwave exposure ranged from 37.2 to 61.4%. The recoveries by MAE were
      comparable to those obtained by the conventional blender extraction technique.
      The precision of the MAE method was demonstrated by relative standard deviations
      of <7% for the three pesticides. The cooked cabbage and tomato samples showed no
      breakdown of the parent compounds, and the recoveries of three pesticides were
      comparable to those obtained with the uncooked samples.

PMID- 14709020
TI  - Kinetics and mechanism of cymoxanil degradation in buffer solutions.
AB  - The kinetics and mechanism(s) of the hydrolytic degradation of a compound are
      needed to evaluate a compound's abiotic degradation in the environment. In this
      paper, the hydrolysis of cymoxanil [2-cyano-N-[(ethylamino)carbonyl]-2
      (methoxyimino) acetamide] was investigated in dark sterile aqueous solutions
      under a variety of pH conditions (pH 2.8-9.2) and temperatures (15-50 degrees C).
      Hydrolysis of cymoxanil was described by first-order kinetics, which was
      dependent on pH and temperature. Cymoxanil degraded rapidly at pH 9 (half-life =
      31 min) and relatively slowly at pH 2.8 (half-life = 722 days). The effect of
      temperature on the rate of cymoxanil degradation was characterized using the
      Arrhenius equation with an estimated energy of activation of 117.1 kJ mol(-)(1).
      An increase in temperature of 10 degrees C resulted in a decrease in half-life by
      a factor of approximately 5. Three competing degradation pathways are proposed
      for the hydrolysis of cymoxanil, with two of the pathways accounting for
      approximately 90% of cymoxanil degradation. These two pathways involved either
      initial cyclization to 1-ethyldihydro-6-imino-2,3,5(3H)-pyrimidinetrione-5-(O
      methyloxime) (1, Figure 1) or direct cleavage of the C-1 amide bond to form
      cyano(methoxyimino) acetic acid (7). The third pathway of degradation involved
      initial cyclization to 3-ethyl-4-(methoxyimino)-2,5-dioxo-4
      imidazolidinecarbonitrile (8), which rapidly degrades into 1-ethyl-5
      (methoxyimino)-2,4-imidazoline-2,4-dione (9). All three pathways eventually lead
      to the formation of the polar metabolite oxalic acid.

PMID- 14709022
TI  - Stereochemical course of the generation of 3-mercaptohexanal and 3
      mercaptohexanol by beta-lyase-catalyzed cleavage of cysteine conjugates.
AB  - The product resulting from the reaction between E-2-hexenal and l-cysteine was
      shown to be a diastereoisomeric mixture of 2-(2-S-l-cysteinylpentyl)-1,3
      thiazolidine-4-carboxylic acid 1. Treatment of the conjugate with two sources of
      cysteine-S-conjugate beta-lyase (tryptophanase from E. coli and a crude enzyme
      extract prepared from Eubacterium limosum) resulted in the formation of 3
      mercaptohexanal. The reaction proceeded with a slight preference for the (S)
      configured product, however, with low conversion rate. The role of 3-S-l
      cysteinylhexanal 2 as substrate for beta-lyases was demonstrated by in situ
      generation of 2 from 3-S-(N-acetyl-l-cysteinyl)hexanal using acylase. Opposite
      enantioselectivity was observed for the liberation of 3-mercaptohexanol from 3-S
      l-cysteinylhexanol 5 by the enzyme preparations from Eubacterium limosum and
      tryptophanase. Various yeasts produced 3-mercaptohexanol starting from 1 as well
      as from 5. The reactions proceeded without preferential formation of one of the
      enantiomers.

PMID- 14709023
TI  - Antioxidant capacity and phenolic content in leaf extracts of tree spinach
      (Cnidoscolus spp.).
AB  - Total phenolic content and antioxidant capacity of two tree spinach species
      (Cnidoscolus chayamansa McVaugh and C. aconitifolius Miller.) were determined in
      raw and cooked leaf extracts. Antioxidant capacity was assessed by the oxygen
      radical absorbance capacity (ORAC) assay, and flavonoid glycoside composition was
      quantified by HPLC and identified by GC. Total phenolics and antioxidant capacity
      were higher in raw than in cooked leaf extracts. The ORAC values were strongly
      correlated with total phenolic content (r = 0.926) in all leaf extracts. The
      major flavonoids isolated from the leaf extracts were kaempferol-3-O-glycosides
      and quercetin-3-O-glycosides. C. aconitifolius leaves contained more varieties of
      the flavonoid glycosides than C. chayamansa. Cooking reduced antioxidant activity
      and phenolic content and resulted in losses of some kaempferol glycoside and
      quercetin glycoside residues in leaf extracts. The results of this study indicate
      that tree spinach leaves are a rich source of natural antioxidants for foods.

PMID- 14709024
TI  - Inhibition of apple polyphenol oxidase activity by procyanidins and polyphenol
      oxidation products.
AB  - The rate of consumption of dissolved oxygen by apple polyphenol oxidase in cider
      apple juices did not correlate with polyphenol oxidase activity in the fruits and
      decreased faster than could be explained by the decrease of its polyphenolic
      substrates. The kinetics parameters of a crude polyphenol oxidase extract,
      prepared from apple (Braeburn cultivar), were determined using caffeoylquinic
      acid as a substrate. Three apple procyanidin fractions of n 80, 10.5, and 4 were
      purified from the parenchyma of cider apples of various cultivars. Procyanidins,
      caffeoylquinic acid, (-)-epicatechin, and a mixture of caffeoylquinic acid and (
      )-epicatechin were oxidized by reaction with caffeoylquinic acid o-quinone in
      order to form oxidation products. All the fractions were evaluated for their
      inhibitory effect on PPO activity. Native procyanidins inhibited polyphenol
      oxidase activity, the inhibition intensity increasing with n. The polyphenol
      oxidase activity decreased by 50% for 0.026 g/L of the fraction of n 80, 0.17 g/L
      of the fraction of n 10.5, and 1 g/L of the fraction of n 4. The inhibitory
      effect of oxidized procyanidins was twice that of native procyanidins. Oxidation
      products of caffeoylquinic acid and (-)-epicatechin also inhibited polyphenol
      oxidase.

PMID- 14709025
TI  - The behavior of deuterium-labeled monolignol and monolignol glucosides in lignin
      biosynthesis in angiosperms.
AB  - To examine the behavior of monolignol and monolignol glucosides in lignin
      biosynthesis, pentadeutero[9-D(2), 3-OCD(3)]coniferyl alcohol and pentadeutero[9
      D(2), 3-OCD(3)]coniferin were synthesized and fed to growing Eucalyptus
      camaldulensis and Magnolia kobus. The differences in the incorporation patterns
      of these labeled precursors were studied using gas chromatography-mass
      spectrometry (GC-MS). Both precursors were incorporated into lignin, but the
      labeled coniferyl alcohol was incorporated more directly, resulting in a high
      proportion of pentadeutero-labeled guaiacyl and syringyl units in newly formed
      xylem, while labeled coniferin tended to be incorporated in lignin as
      tetradeutero units, especially in syringyl lignin in both trees. However, the
      incorporation efficiencies of the precursors into syringyl lignin were higher in
      Magnolia than in Eucalyptus, and the ratios of tetradeutero to pentadeutero in
      guaiacyl lignin were lower in Magnolia than in Eucalyptus when the trees were fed
      coniferin.

PMID- 14709026
TI  - In vitro gastrointestinal digestion study of broccoli inflorescence phenolic
      compounds, glucosinolates, and vitamin C.
AB  - Broccoli (Brassica oleracea L. var. italica cv. Marathon) inflorescences are a
      good source of bioactive compounds, such as phenolics (flavonoids and
      hydroxycinnamoyl derivatives), glucosinolates, and vitamin C. In this work, these
      health-promoting compounds were submitted to digestion under in vitro
      gastrointestinal conditions (pH, temperature, enzyme, and chemical conditions).
      This technique differentiated among the compounds associated with macromolecules
      in soluble and insoluble form and those that are freely soluble. In addition, it
      evaluates the chemical stability of the broccoli compounds under simulated
      physiological conditions. The gastric digestion of broccoli caused high losses in
      glucosinolates (69% loss), whereas phenolics and vitamin C presented higher
      stability under these conditions. Thus, there were no losses in flavonoids, a 7%
      loss of vitamin C, and a variable rate of loss (6-25%) in hydroxycinnamic acid
      derivatives. The stability of all of the compounds was affected by the in vitro
      intestinal conditions. Under the in vitro conditions, flavonoids and
      hydroxycinnamoyl acid derivatives were of low availability, due to their
      significant losses under these conditions, at the end of the experiment (84 and
      80% loss, respectively). Vitamin C was the metabolite that showed the greater
      decrease after intestinal digestion (91% loss). Regarding the remaining
      glucosinolates, these compounds presented higher stability under intestinal
      conditions, rendering an availability similar to that found for phenolics (75%
      loss). Therefore, broccoli components were affected by gastric and/or intestinal
      conditions depending on the type of compound. Thus, glucosinolates were mainly
      degraded by gastric conditions, whereas phenolic compounds and vitamin C were
      degraded by intestinal conditions.

PMID- 14709027
TI  - Inhibition of peroxynitrite-mediated reactions by vanillin.
AB  - Several neurodegenerative diseases such as Alzeimer's and Parkinson's as well as
      septic shock and inflammation involve formation of reactive oxygen and nitrogen
      species that include peroxynitrite (PON). PON can also react with endogenous
      antioxidants. Therefore, dietary supplementation with antioxidants may help in
      these diseases. An exogenous antioxidant, vanillin (4-hydroxy-3
      methoxybenzaldehyde), used widely as a food flavoring agent, was evaluated for
      its ability to scavenge PON and inhibit PON-mediated reactions. Nitration of
      tyrosine by PON was assessed by high-performance liquid chromatography (HPLC).
      This reaction was inhibited by vanillin. The oxidation of dihydrorhodamine 123 to
      fluorescent rhodamine 123 was also inhibited by vanillin. The kinetics of
      reaction between PON and vanillin was studied by stopped-flow technique. The
      products of this reaction were analyzed by HPLC, and hydroxyvanillin was
      identified as one of the five products with absorption at 350 nm. These data
      demonstrate that vanillin effectively scavenges PON in cell-free systems.

PMID- 14709028
TI  - Comment on comparison of the total phenolic and ascorbic aid content of freeze
      dried and air-dried marionberry, strawberry, and corn grown using conventional,
      organic, and sustainable agricultural practices.

PMID- 14709030
TI  - Design of a synthetic foldamer that modifies the growth of calcite crystals.
AB  - An oligopyridine foldamer, whose structure is dictated by bifurcated hydrogen
      bonds, was designed to recognize the surface of calcite through three
      carboxylates, projected from one face of the molecule. At low concentrations of
      the trimer, elongated calcite crystals with angular, teeth-like growths,
      identified as {0l} faces, were exclusively formed. In the presence of a related
      monomer, only calcite rhombohedra are formed, indicating that it is the ordered
      array of carboxylates that causes the morphological changes, via a specific
      interaction between the foldamer and the newly expressed faces of the growing
      calcite crystals.

PMID- 14709031
TI  - High affinity, paralog-specific recognition of the Mena EVH1 domain by a
      miniature protein.
AB  - Many protein domains involved in cell signaling contain or interact with proline
      rich sequences, and the design of molecules that perturb signaling pathways
      represents a foremost goal of chemical biology. Previously we described a protein
      design strategy in which the well-folded alpha-helix in avian pancreatic
      polypeptide (aPP) presents short alpha-helical recognition epitopes. The
      miniature proteins designed in this way recognize even shallow protein clefts
      with high affinity and specificity. Here we show that the well-folded type-II
      polyproline helix in aPP can present the short PPII-helical recognition epitope
      within the ActA protein of Listeria monocytogenes. Like miniature proteins that
      use an alpha-helix for protein recognition, the miniature protein designed in
      this way displays high affinity for a natural ActA target, the EVH1 domain Mena1
      112, and achieves the elusive goal of paralog specificity, discriminating well
      between EVH1 domains Mena1-112, VASP1-115, and Evl1-112. Most importantly, the
      miniature protein competed with ActA in Xenopus laevis egg cytoplasmic extracts,
      decreasing actin-dependent motility of L. monocytogenes and causing extreme speed
      variations and discontinuous tail formation. Our results suggest that miniature
      proteins based on aPP may represent an excellent framework for the design of
      ligands that differentiate the roles of EVH1 domains in vitro and in vivo.

PMID- 14709032
TI  - Probing glycosyltransferase activities with the Staudinger ligation.
AB  - The development of rapid screening methods for probing glycosyltransferase
      activities is essential for advancing the field of glycobiology. While assays for
      specific glycosyltransferases exist, there is no generalizable method that can be
      applied across the enzyme superfamily. Herein we describe a novel
      glycosyltransferase assay that exploits their unnatural substrate tolerance and
      the unique chemical reactivity of the azide. We applied this "azido-ELISA" to the
      family of polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs), all
      of which were able to transfer N-azidoacetylgalactosamine (GalNAz) from the
      unnatural nucleotide sugar donor UDP-GalNAz. The azide was detected and
      quantified by Staudinger ligation with a phosphine probe in a microtiter plate
      format. This approach should be applicable to any glycosyltransferase or group
      transfer enzyme that tolerates unnatural azido substrates.

PMID- 14709033
TI  - A systematic study of CO oxidation on metals and metal oxides: density functional
      theory calculations.
AB  - CO oxidation on Ru(0001), Rh(111), Pd(111), Os(0001), Ir(111), Pt(111), and their
      corresponding metal oxides is studied using density functional theory. It is
      found that (i) the reactivity of metal oxide is generally higher than that of the
      corresponding metal, and (ii) on both metals and metal oxides, the higher the
      chemisorption energy is in the initial state, the larger the reaction barrier.
      The barriers are further analyzed by decomposing them into electronic and
      geometric effects, and the higher reactivity of metal oxides is attributed mainly
      to the surface geometric effect. Moreover, the electronic effect on both metals
      and metal oxides follows the same pattern: the shorter the OC-O bond distance in
      the TS, the higher the barrier.

PMID- 14709034
TI  - Polymer-initiated photogeneration of silver nanoparticles in SPEEK/PVA films:
      direct metal photopatterning.
AB  - Cross-linking of sulfonated poly(ether-ether)ketone-poly(vinyl alcohol) (SPEEK
      PVA) materials yields flexible polymer films, possessing high light-sensitivity
      and ion-exchange capabilities. Adsorbed Ag+ ions are photoreduced in the film
      under illumination (lambda = 350 nm), leading to metal nanoparticle formation in
      places where the film has been exposed to the light. Nanoparticles form via
      reduction of Ag+ by the polymeric alcohol radicals, generated in the system as a
      result of photochemical H-abstraction from PVA molecules by the excited carbonyl
      triplet state of SPEEK. Use of the films for direct metal photopatterning is
      demonstrated.

PMID- 14709035
TI  - Emission energy correlates with inverse of gold-gold distance for various
      [Au(SCN)2]- salts.
AB  - A series of bis(thiocyanato)gold(I) complexes with Au-Au interactions show
      luminescence in the range from 500 to 670 nm. The series of salts correlates
      emission energy with the reciprocal of the Au-Au distance. As the Au-Au distance
      increases, the emission energy decreases. The ligand system provides no framework
      for the Au-Au interaction. The emission energy seems totally determined by the Au
      Au distance.

PMID- 14709036
TI  - Catalytic asymmetric acyl halide-aldehyde cyclocondensation reactions of
      substituted ketenes.
AB  - Catalytic asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions of
      alkyl-substituted ketenes with structurally diverse aldehydes provide cis
      disubstituted beta-lactones with high enantioselectivity. The AAC reactions
      utilize a novel Al(III)-triamine catalyst in which the metal's dynamic
      coordination geometry leads to a highly selective catalyst complex. These AAC
      reactions represent a functional solution to highly enantioselective substituted
      ester enolate aldol additions.

PMID- 14709037
TI  - Halogen bonding: a new interaction for liquid crystal formation.
AB  - It is shown for the first time that liquid crystal behavior can be induced
      through halogen bonding. Thus, mixing the nonmesomorphic components 4
      alkoxystilbazole with pentafluoroiodobenzene leads to a 1:1 halogen-bonded
      complex whose integrity is shown by X-ray single-crystal analysis and which shows
      thermotropic smectic A and nematic phases.

PMID- 14709038
TI  - Catalytic sulfoxidation and epoxidation with a Mn(III) triazacorrole: evidence
      for a "third oxidant" in high-valent porphyrinoid oxidations.
AB  - The reaction between (TBP)8(Cz)Mn(III) (1) and the oxygen atom donors
      iodosylbenzene (PhIO) or p-cyanodimethylaniline-N-oxide (CDMANO) leads to the
      manganese(V)-oxo complex (TBP)8(Cz)Mn(V)O (2), which has been isolated and
      characterized previously. Under catalytic conditions with 1 as added catalyst and
      PhIO as oxidant, both sulfoxidation of PhSMe and epoxidation of cis-stilbene is
      observed, whereas with CDMANO no sulfoxidation takes place, suggesting that 2 is
      not the active oxidant. Examination of the independent reactivity of isolated 2
      toward PhSMe and cis-stilbene supports this conclusion. A mechanism which relies
      on a novel type of oxidant involving Lewis acid activation of PhIO by the Mn(V)
      oxo complex 2 accounts for these observations and is confirmed by 18O-labeling
      experiments.

PMID- 14709039
TI  - In vitro evolution of functional DNA using capillary electrophoresis.
AB  - Electrophoretic selection with capillary electrophoresis (CE) is used, for the
      first time, to isolate functional nucleic acid sequences using SELEX (systematic
      evolution of ligands by exponential enrichment). SELEX uses molecular evolution
      to select functional sequences (aptamers) from random RNA or DNA libraries.
      Conventional SELEX is usually performed with affinity chromatography, which may
      introduce significant bias into the selection step. Important biases include the
      slow kinetics involved in the elution of strongly bound sequences and performing
      the selection with the target molecule tethered to the stationary support, not in
      free solution. In this novel CE-SELEX approach, selection occurs in free
      solution. The nucleic acid sequences that bind the target undergo a mobility
      shift, migrating at a different rate, allowing them to be separated from the
      inactive sequences. Thus, there is no need to wash the active sequences off a
      column as in conventional SELEX, eliminating any kinetic bias. In this work, the
      viability of CE-SELEX was demonstrated by performing selections against
      immunoglobulin E (IgE). Anti-IgE aptamers with dissociation constants as low as
      40 nM were obtained in only two rounds of selection.

PMID- 14709040
TI  - In vivo synthesized proteins with monoexponential fluorescence decay kinetics.
AB  - Tryptophan, when in a protein, typically shows multiexponential fluorescence
      decay kinetics. Complex kinetics prevents a straightforward interpretation of
      time-resolved fluorescence protein data, particularly in anisotropy studies or if
      the effect of a dynamic quencher or a resonance energy transfer (RET) acceptor is
      investigated. Here, time-resolved fluorescence data are presented of an isosteric
      tryptophan analogue, 5-fluorotryptophan, which when biosynthetically incorporated
      in proteins shows monoexponential decay kinetics. Data are presented indicating
      that the presence of a fluoro atom at the 5-position suppresses the electron
      transfer rate from the excited indole moiety to the peptide bond. This process
      has been related to the multiexponential fluorescence decay of tryptophan in
      proteins. The monoexponential decay of 5-fluorotryptophan makes it possible to
      measure simultaneously multiple distances between 5-fluorotryptophan and a RET
      acceptor. We demonstrate that for an oligomeric protein, consisting of two single
      tryptophan-containing subunits, the individual distances between 5
      fluorotryptophan and the single substrate binding site can be resolved using a
      substrate harboring a RET acceptor.

PMID- 14709041
TI  - Substituent effects and nearly degenerate transition states: rational design of
      substrates for the tandem Wolff-Cope reaction.
AB  - The substrate scope for a ketene-assisted Cope (tandem Wolff-Cope) reaction is
      elucidated from first-principles quantum mechanics. An alternate pathway (trans)
      leading to an undesired and unstable product lies perilously close (
      approximately 2.5 kcal/mol) to the primary (cis) reaction pathway; this near
      degeneracy arises from preferential ketene stabilization of a radicaloid trans
      transition state over an aromatic cis transition state. Normally, substitution at
      "forbidden" sites causes the alternate pathway to be favored and the reaction to
      fail, but using simple conformational analysis principles we design substrates
      that defy this rule.

PMID- 14709042
TI  - Nanoparticles from cationic copolymer and DNA that are soluble and stable in
      common organic solvents.
AB  - DNA by virtue of its superlative ability to self-assemble has found use beyond
      biological research in the design and fabrication of nanomaterials. However,
      developing novel DNA-based materials for chemical applications might be
      restricted due to the insoluble nature of DNA in most common organic solvents. In
      this Communication, we are reporting the first demonstration of making DNA
      soluble in a variety of nonbiological solvents such as acetonitrile, benzene,
      dimethyl sulfoxide (DMSO), and tetrahydrofuran with the help of poly(ethylene
      glycol) (PEG)-based cationic random copolymers. Because of complex formation
      between cationic copolymer and anionic DNA, nanoparticles are formed. These
      nanoparticles are expected to exhibit micelle-like structures with a nanometric
      core of cationic units neutralized by phosphate anions of DNA, surrounded by a
      shell of PEG segments. As PEG is soluble in the organic solvents used in this
      study, nanoparticles are stable in these solvents, making entrapped DNA soluble
      in these organic solvents.

PMID- 14709043
TI  - A new patterning method using photocatalytic lithography and selective atomic
      layer deposition.
AB  - We report a new patterning method using photocatalytic lithography of
      alkylsiloxane self-assembled monolayers and selective atomic layer deposition of
      thin films. The photocatalytic lithography is based on the fact that the
      decomposition rate of the alkylsiloxane monolayers in contact with TiO2 is much
      faster than that with SiO2 under UV irradiation in air. The photocatalytic
      lithography, using a quartz plate coated with patterned TiO2 thin films, was done
      to prepare patterned monolayers of the alkylsiloxane on Si substrates. A ZrO2
      thin film was selectively deposited onto the monolayer-patterned Si substrate by
      atomic layer deposition.

PMID- 14709044
TI  - Reversible modulation of quantum dot photoluminescence using a protein- bound
      photochromic fluorescence resonance energy transfer acceptor.
AB  - Multiple copies ( approximately 20) of Escherichia coli maltose binding protein
      (MBP) were coordinated to luminescent semiconductor quantum dots (QDs) via a C
      terminal oligohistidine segment. The MBP was labeled with a sulfo-N
      hydroxysuccinimide-activated photochromic BIPS molecule (1',3-dihydro-1'-(2
      carboxyethyl)-3,3-dimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-(2H)-indoline]) at
      two different dye-to-MBP ratios; D/P = 1 and 5. The ability of MBP-BIPS to
      modulate QD photoluminescence was tested by switching BIPS from the colorless
      spiropyran (SP) to the colored merocyanine (MC) using white light (>500 nm) or UV
      light ( approximately 365 nm), respectively. QDs surrounded by MBP-BIPS with D/P
      = 1 were quenched on average approximately 25% with consecutive repeated
      switches, while QDs surrounded by MBP-BIPS with D/P = 5 were quenched
      approximately 60%. This result suggests a possible use of BIPS-labeled proteins
      in QD-based nanostructures as part of a threshold switch or other biosensing
      device.

PMID- 14709045
TI  - Microporous manganese formate: a simple metal-organic porous material with high
      framework stability and highly selective gas sorption properties.
AB  - Novel microporous metal-organic framework material composed of Mn(II) and formate
      ions displays permanent porosity, high thermal stability, and size-selective gas
      sorption behavior. The framework is stable enough to maintain single
      crystallinity after the complete guest removal at 150 degrees C under a reduced
      pressure. Most importantly, it selectively adsorbs H2 and CO2 but not N2 and
      other gases with larger kinetic diameters, which appears to be due to the small
      aperture of the channels. Despite a moderate H2 storage capacity, which is
      however still higher than that of any zeolite, its H2 surface coverage is one of
      the highest among the known microporous materials. Thus this new zeolite-like
      material made of a simple organic building block may find useful applications in
      gas separation and sensor.

PMID- 14709046
TI  - A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug
      discovery by intentional lead hybridization.
AB  - We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM)
      non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational
      hybridization of two structurally distinct leads. Two micromolar inhibitors were
      discovered by a parallel rational design and random screening program, and
      individual crystal structures of bovine ADA in complexation with these inhibitors
      revealed several unknown binding sites and distinct binding modes. Using this
      information as the starting point, highly effective lead hybridization was
      achieved in only two structure-based drug design iterations. The conceptual
      approach illustrated by this example promises to be broadly useful in the search
      for new chemical entities and can contribute greatly to improve the overall
      efficiency and speed of drug discovery.

PMID- 14709047
TI  - Fluorous mixture synthesis of stereoisomer libraries: total syntheses of (+)
      murisolin and fifteen diastereoisomers.
AB  - The synthesis of a stereoisomer library of 16 murisolins in individual pure form
      by fluorous mixture synthesis is reported. Four stereoisomeric precursors are
      tagged with different fluorous tags, and the resulting mixture is taken through
      the synthesis with four splits and late stage demixing and detagging to give all
      16 products. These products exhibit only six different sets of NMR spectra, but
      all can be differentiated by chiral HPLC. The structure of murisolin is
      confirmed, but the structures of murisolin A and 16,19-cis-murisolin may never be
      known with certainty because insufficient data were collected on natural samples
      to differentiate each of them from one other isomer.

PMID- 14709048
TI  - The nature of the surface species formed on Au/TiO2 during the reaction of H2 and
      O2: an inelastic neutron scattering study.
AB  - Inelastic neutron spectroscopy (INS) has been employed to identify surface
      species formed during the H2-O2 reaction on Au/TiO2 catalysts. Determination of
      the surface intermediates formed in this reaction is crucial to develop a
      mechanistic understanding for the direct vapor-phase propylene epoxidation
      reaction and synthesis of H2O2. Although the presence of intermediate hydroperoxo
      species (during these reactions) has been suggested in literature, it has never
      been demonstrated. Our studies provide direct evidence for the formation of
      surface hydroperoxo species during the H2-O2 reaction.

PMID- 14709049
TI  - 2',5'-linked DNA is a template for polymerase-directed DNA synthesis.
AB  - Genomes are composed of nucleic acids bearing 3',5'-phosphodiester-linked sugars.
      The 2',5'-phosphodiester linkage is a fundamental alternative to the natural
      linkage and is the predominant product of most nontemplate, nonenzymatic
      oligomerizations of nucleotide monomers. This fact suggests a chemical bias for
      the formation of 2',5'-phosphodiester bonds, an important consideration in the
      context of molecular evolution on Earth or elsewhere. Although 2',5'-linked RNA
      occurs naturally, it is evidently not used to encode genetic information.
      Nevertheless, the capacity of the 2',5'-phosphodiester linkage to serve as a
      genetic material has been probed in laboratory experiments. Initial studies
      examined both self-pairing and pairing with natural nucleic acids. These studies
      showed that, while 2',5'-linked DNA and RNA form double and triple helices with
      themselves, their interactions with natural nucleic acids are asymmetric-pairing
      is seen with 3',5'-linked RNA but not DNA. Although the ability to form a stable
      structure (such as a helix) is likely a necessary condition for nonenzymatic
      information transfer, in the case of enzymatic reactions this precondition may be
      expected to be lifted in cases where the enzyme can serve as a "template for the
      template" and make up for structural deficiencies that would be fatal to its
      abiotic counterpart. In support of this suggestion, we demonstrate that 2',5'
      linked DNA is a template for enzymatic synthesis of natural DNA with a variety of
      DNA polymerases and reverse transcriptases directing the incorporation of all
      four natural nucleotides with fidelity.

PMID- 14709050
TI  - Divalent ansa-zirconocenes: stereoselective synthesis and high activity for
      propylene polymerization.
AB  - The reduction of ZrCl4(PR3)2 with Li powder, in the presence of a stoichiometric
      amount of trans-1,4-diphenyl-1,3-butadiene, affords the Zr(II) diene complexes
      (1) in 90-93% yields. This reaction consists of a rate-limiting step for the
      formation of the chloride-bridged Zr(III) dimer (2) and a fast diene-driven
      disproportionation of 2 to 1 and ZrCl4(PR3)2 that re-enters the reduction cycle.
      The reaction of 1 with Li2{Me2Si(2-Me-4-Ph-Ind)2} in toluene produces
      quantitatively the desired racemic, divalent ansa-zirconocene (3) that is a
      highly active isospecific propylene polymerization catalyst upon activation with
      common activators.

PMID- 14709051
TI  - The role of proton donors in SmI2-mediated ketone reduction: new mechanistic
      insights.
AB  - The effects of proton donors (alcohols and water) on the rate of reduction of
      acetophenone by SmI2 have been examined utilizing stopped-flow spectrophotometric
      studies. The rate orders with respect to proton source and the kinetic isotope
      effects were determined as well. The reaction was first-order in phenol, 2,2,2
      trifluoroethanol, methanol, and ethanol and zero-order in 2-propanol and 2-methyl
      2-propanol when 25 equiv of proton source were used in the reduction. Methanol,
      ethanol, 2,2,2-trifluoroethanol, and phenol also showed a direct correlation
      between the pKa of the alcohol and the rate of reduction. Under the same
      conditions, water had a fractional rate order of 1.4. Further studies showed that
      water has a rate order of 1 at lower concentrations (<8 equiv) and a rate order
      of 2 at higher concentrations (>80 equiv). These results clearly indicate that
      the nature of the proton donor and its concentration affects the rates of
      reduction. Water has a high affinity for SmI2 (compared to that of the alcohols),
      and the onset of coordination at relatively low concentrations channels the
      reaction through a mechanistically distinct pathway.

PMID- 14709052
TI  - Elucidating the mechanism of cis double bond formation in epothilone
      biosynthesis.
AB  - The epothilones, originally isolated from the myxobacterium Sorangium cellulosum,
      are macrocyclic compounds that are synthesized by a modular polyketide synthase,
      an enzyme complex composed of six large, multifunctional proteins. The
      penultimate intermediates in epothilone production, and the products of the PKS
      catalyzed reactions, are epothilones D and C, which contain a 12,13-cis-double
      bond. The 12 and 13 positions of epothilones are generated during the fourth
      elongation step that is governed by module 4. Module 4 does not contain a
      dehydratase (DH) domain, which is required for dehydration to create the double
      bond. A DH domain, present in module 5 and presumed to act in the fifth
      elongation step at the 10 and 11 positions, was proposed to act as well to
      generate the 12,13-cis-double bond. Inactivation of the DH domain in module 5
      resulted in the production of 10,11-dehydro-13-hydroxyepothilone D as the major
      product, confirming that DH5 is required for 12,13 dehydration. A mechanistic
      model based on domain skipping and modular stuttering is presented to explain the
      basis for the iterative DH5 activity observed.

PMID- 14709053
TI  - A formal synthesis of (-)-mycalamide A.
AB  - Novel strategies are developed for an efficient formal synthesis of (-)
      mycalamide A. The left-hand side (-)-7-benzoylpederic acid is synthesized from
      (2S,3S)-2,3-epoxybutane. The key features include a highly regioselective Ru
      catalyzed alkene-alkyne coupling reaction and a novel way to control the
      challenging C(7) stereocenter. The right-hand side was synthesized from (R)
      pantolactone. The complex trioxodecalin core is constructed with two Pd(0)
      catalyzed O-pi-allyl cyclizations. The first one is chemoselective, while the
      second one is highly diastereoselective. Three additional steps would be required
      to complete a total synthesis of (-)-mycalamide A.

PMID- 14709055
TI  - A switchable self-doped polyaniline: interconversion between self-doped and non
      self-doped forms.
AB  - A novel strategy for the synthesis of a substituted polyaniline that can be
      switched between a self-doped and non-self-doped state is presented. The approach
      uses the complexation between boronic acid-substituted aniline, a diol (d
      fructose), and fluoride to generate an anionic monomer. Under these conditions,
      chemical polymerization results in a self-doped, water-soluble, conducting
      polyaniline under neutral aqueous conditions. The self-doped polymer can be
      simply and reversibly converted to an insoluble non-self-doped form by reducing
      the concentration of fluoride. Characteristics of the polymerization reaction and
      the resulting polymer are discussed.

PMID- 14709054
TI  - Gated electron transfer as a probe of the configurational dynamics of peptide
      protein complexes.
AB  - Gated electron-transfer measurements are used to probe the configurational
      dynamics of complexes formed between small metallopeptides and cytochrome c. The
      results show that that an apparently subtle chemical alteration of the
      metallopeptide produces significant changes to the dynamics of the peptide
      protein complex.

PMID- 14709056
TI  - Biomolecule-assisted synthesis of highly ordered snowflakelike structures of
      bismuth sulfide nanorods.
AB  - A biomolecule-assisted simple technique has been developed for the spontaneous
      ordering of the Bi2S3 nanorods into snowflakelike superstructures in high yield
      under microwave-hydrothermal conditions. In this method, glutathione (GSH) is
      used as both an assembling agent and a sulfur source. By controlling the molar
      ratio between bismuth nitrate and glutathione as well as the synthetic
      temperature, several kinds of Bi2S3 one-dimensional nanomaterials such as
      snowflakelike structures, nanowires constructed of particles, short nanorods, and
      fine and long nanowires have been controllably synthesized.

PMID- 14709057
TI  - A dramatic elongation of the lifetime of charge-separated state by complexation
      with yttrium triflate in ferrocene-anthraquinone linked dyad.
AB  - Seven million times elongation of the lifetime of charge-separated state is
      attained in the presence of yttrium triflate [Y(OTf)3] in the photoinduced
      electron-transfer reaction of a ferrocene-anthraquinone dyad (Fc-AQ) with a rigid
      amide spacer in benzonitrile at 298 K as compared with the lifetime in its
      absence. Such remarkable elongation of the CS lifetime in the presence of Y(OTf)3
      results from the strong binding of Y(OTf)3 with the AQ*- moiety of Fc+-AQ*-.

PMID- 14709058
TI  - A stable radical-substituted radical cation with strongly ferromagnetic
      interaction: nitronyl nitroxide-substituted 5,10-diphenyl-5,10-dihydrophenazine
      radical cation.
AB  - A stable radical-substituted radical ion with strongly ferromagnetic
      intramolecular interaction (J) between the radical and radical ion sites is an
      attractive spin building block of organic magnets. We prepared 2-nitronyl
      nitroxide-substituted 5,10-diphenyl-5,10-dihydrophenazine radical cation, 1+. The
      1+ salt was stable under aerated conditions at room temperature and had a large
      J/kB value (>/=+700 K).

PMID- 14709059
TI  - Synthesis and structure of 1-zirconacyclopent-3-yne complexes without
      substituents adjacent to the triple bond.
AB  - Five-membered metallacyclic alkynes that have no substituents adjacent to the
      triple bond have been synthesized, isolated, and structurally characterized.
      Zirconocene dichlorides, Cp'2ZrCl2 (Cp' = C5H5, C5H4-t-Bu), reacted with 1,4
      dichlorobut-2-yne in the presence of magnesium to give 1-zirconacyclopent-3-yne
      compounds (5 (a) Cp' = C5H5, (b) Cp' = C5H4-t-Bu) that have a -CH2CCCH2- moiety
      in good yields. They are stable enough to be isolated in a pure form, despite the
      absence of substituents. 5a reacted with an equimolar amount of Cp2Zr(but-1
      ene)(PMe3) to produce a bimetallic complex in which the zirconacyclopentyne
      coordinates to the other zirconocene moiety as an alkyne.

PMID- 14709060
TI  - Reversible super-hydrophobicity to super-hydrophilicity transition of aligned ZnO
      nanorod films.
AB  - Remarkable surface wettability transition occurs with an inducement of
      ultraviolet (UV) for aligned ZnO nanorod films. The inorganic oxide films, which
      show super-hydrophobicity (left), become super-hydrophilic (right) when exposed
      to UV illumination. After the films are placed in the dark, the wettability
      evolves back to super-hydrophobicity. This reversible effect is ascribed to the
      cooperation of the surface photosensitivity and the aligned nanostructure. Such
      special property will greatly extend the applications of ZnO films.

PMID- 14709061
TI  - Recognition of G-1:C73 atomic groups by Escherichia coli histidyl-tRNA
      synthetase.
AB  - This work focuses on the RNA-protein interactions necessary for efficient
      aminoacylation of tRNAHis by Escherichia coli histidyl-tRNA synthetase (HisRS).
      The E. coli tRNAHis acceptor stem is characterized by a unique "extra" G-1:C73
      base pair. Previous in vivo and in vitro studies showed that G-1:C73 is a major
      recognition element for E. coli HisRS. To further probe the role of the G-1:C73
      base pair in specific aminoacylation, we carried out atomic group "mutagenesis"
      studies. Systematic base analogue substitutions at the -1:73 position of
      chemically synthesized microhelixHis substrates suggest that the G-1 base serves
      to position the 5'-monophosphate, which is critical for aminoacylation.
      Additionally, the C73 and G-1 bases contain major groove exocyclic atomic groups
      that contribute to HisRS recognition.

PMID- 14709062
TI  - Measurement of five dipolar couplings from a single 3D NMR multiplet applied to
      the study of RNA dynamics.
AB  - A new three-dimensional NMR experiment is described that yields five scalar or
      dipolar couplings from a single cross-peak between three spins. The method is
      based on the E.COSY principle and is demonstrated for the H1'-C1'-C2' fragment of
      ribose sugars in a uniformly 13C-enriched 24-nucleotide RNA stem-loop structure,
      for which a complete set of couplings was obtained for all nonmodified
      nucleotides. The values of the isotropic J couplings and the 13C1' and 13C2'
      chemical shifts define the sugar pucker. Once the sugar pucker is known, the five
      dipolar couplings between C1'-H1', C2'-H2', H1'-H2', C1'-H2', and C2'-H1',
      together with C1'-C2', C3'-H3', and C4'-H4' available from standard experiments,
      can be used to derive the five unknowns that define the local alignment tensor,
      thereby simultaneously providing information on relative orientation and dynamics
      of the ribose units. Data indicate rather uniform alignment for all stem
      nucleotides in the 24-nt stem-loop structure, with only a modest reduction in
      order for the terminal basepair, but significantly increased mobility in part of
      the loop region. The method is applicable to proteins, nucleic acids, and
      carbohydrates, provided 13C enrichment is available.

PMID- 14709063
TI  - Fragmentation of the conjugate base of 2-(1-hydroxybenzyl)thiamin: does
      benzoylformate decarboxylase prevent orbital overlap to avoid it?
AB  - The base-catalyzed addition of thiamin to benzaldehyde produces 2-(1
      hydroxybenzyl)thiamin (HBnT), but in neutral solution HBnT undergoes base
      catalyzed irreversible fragmentation into pyrimidine and thiazole derivatives.
      The fragmentation (rather than elimination) occurs in proportion to the extent
      that N1' is protonated or alkylated. Generating the conjugate base of HBnT by
      decarboxylation surprisingly leads to fragmentation independent of the state of
      N1'. Therefore, a cationic state at N1' specifically promotes removal of the
      C2alpha proton rather than the fragmentation process itself. It is suggested that
      benzoylformate decarboxylase, which generates a similar intermediate, exerts
      stereoelectronic control of the conformation of the carbanion, blocking
      fragmentation and facilitating protonation.

PMID- 14709064
TI  - Formation and stability of a Janus-Wedge type of DNA triplex.
AB  - A new type of DNA targeting with the formation of a Janus-Wedge (J-W) triple
      helix is described. The "wedge" residue (W) attached to a PNA backbone is
      designed to insert itself into double-stranded DNA and base pair with both Watson
      Crick faces. To study the stability of such an assembly, we have examined the
      formation of the J-W triplex with dC8 - T8 target sequence. The use of this
      target sequence permits the study of this new helix form without competing Watson
      Crick interactions between the two target residues. Studies indicate that the W
      strand binds to both target strands, with defined polarity and a stability (-15.2
      kcal/mol) that is roughly the sum of the two independent duplex interactions.

PMID- 14709065
TI  - An efficient direct alpha-alkylation of ketones with primary alcohols catalyzed
      by [Ir(cod)Cl]2/PPh3/KOH system without solvent.
AB  - alpha-Alkylation of ketones was successfully achieved by the reaction of ketones
      with alcohols catalyzed by iridium complexes in the presence of a small amount of
      base. For example, 2-octanone was allowed to react with butanol under the
      influence of [Ir(cod)Cl]2/PPh3/KOH to give 6-dodecanone in good yield. The
      reaction was found to proceed by using a 1:1 mixture of ketone and alcohol
      without use of any solvent.

PMID- 14709066
TI  - Poly(fluoroalkyl acrylate)-bound ruthenium carbene complex: a fluorous and
      recyclable catalyst for ring-closing olefin metathesis.
AB  - The synthesis of a fluorous olefin metathesis catalyst derived from the Grubbs
      second-generation ruthenium carbene complex is described. The air stable fluorous
      polymer-bound ruthenium carbene complex 1 shows high reactivity in effecting the
      ring-closing metathesis of a broad spectrum of diene and enyne substrates leading
      to the formation of di-, tri-, and tetrasubstituted cyclic olefins in minimally
      fluorous solvent systems (PhCF3/CH2Cl2, 1:9-1:49 v/v). The catalyst can be
      readily separated from the reaction mixture by fluorous extraction with FC-72 and
      repeatedly reused. The practical advantage offered by the fluorous catalyst is
      demonstrated by its sequential use in up to five different metathesis reactions.

PMID- 14709067
TI  - Lateral quantized charge transfer across nanoparticle monolayers at the air/water
      interface.
AB  - Lateral quantized charge transfer was observed with gold nanoparticle monolayers
      at the air/water interface. The electronic conductivity was measured by using an
      interdigitated arrays (IDA) electrode perpendicularly aligned at the air/water
      interface where a particle ensemble was trapped between the IDA fingers. The
      overall voltammetric responses were analogous to that of the Coulomb blockade
      with a relatively flat central gap. This gap was found to shrink with increasing
      surface pressure. Differential pulse voltammetry revealed a series of well
      defined voltammetric peaks within this central gap, which are ascribed to the
      single electron transfer of the particle ensemble. This observation was
      interpreted on the basis of relatively weak electronic coupling between
      neighboring particles where the particles behave more individually.

PMID- 14709068
TI  - A new reaction sequence involving palladium-catalyzed unsymmetrical aryl
      coupling.
AB  - Biphenylylalkenes containing an ortho substituent in one ring and a different
      ortho-, meta-, or para-substituent in the other are prepared in satisfactory
      yield from an ortho-substituted aryl iodide, an ortho-, meta-, or para
      substituted aryl bromide, a terminal olefin, and a base in DMF under the joint
      catalytic action of palladium(0) and norbornene.

PMID- 14709069
TI  - Establishing the parabolic relationship between reactivity and activity for
      derivatives and analogues of the duocarmycin and CC-1065 alkylation subunits.
AB  - The preparation of a novel series of N-aryl CBI derivatives is detailed in which
      an aryl para substituent could be used to predictably modulate the reactivity of
      the resulting CC-1065/duocarmycin alkylation subunit analogue (rho = 0.17). The
      derivatives were found to be exceptionally stable and to exhibit a well-defined
      relationship between reactivity and cytotoxic potency. When combined with the
      results of an extensive series of N-acyl CBI analogues and derivatives assembled
      over the past 15 years, the studies define a fundamental parabolic relationship
      between reactivity and cytotoxic potency.

PMID- 14709070
TI  - Cross-couplings of alkyl electrophiles under "ligandless" conditions: Negishi
      reactions of organozirconium reagents.
AB  - This report establishes that simple, "ligandless" palladium complexes can
      catalyze the first zirconium-Negishi reactions of alkyl electrophiles. In view of
      the attractiveness of ligandless catalysts (cost, simplicity, and ease of
      purification), these observations add a significant and intriguing new dimension
      to the development of effective palladium-based processes for coupling alkyl
      electrophiles.

PMID- 14709071
TI  - Copper(I)-catalyzed disilylation of alkylidene malonates employing a Lewis base
      activation strategy.
AB  - The disilylation of activated alpha,alpha-unsaturated esters has been
      accomplished by utilizing symmetrical disilanes and catalytic quantities of
      copper(I) salts in the presence of Lewis bases such as DMF. This new methodology
      with various alkylidene malonates is moderate to high yielding and affords alpha
      silyl diesters, compounds that previously have not been readily accessible, that
      can be further manipulated to cleanly afford useful alpha-substituted alpha
      hydroxy esters.

PMID- 14709072
TI  - Low 13C-background for NMR-based studies of ligand binding using 13C-depleted
      glucose as carbon source for microbial growth: 13C-labeled glucose and 13C
      forskolin binding to the galactose-H+ symport protein GalP in Escherichia coli.
AB  - Obtrusive 13C-backgrounds can be a problem in 13C NMR-based studies of ligand
      binding to bacterial membrane transport proteins in their natural state in inner
      membranes. This is largely solved for the bacterial galactose-H+ symport protein
      GalP by growing the producing organism Escherichia coli on 13C-depleted glucose
      (13C </= 0.07%) as the main carbon source. 13C solid-state NMR-based binding
      studies for the inhibitor forskolin 1 and the transported substrate glucose 2,
      both singly labeled with 13C, are reported and discussed. For 1, tight binding is
      observed, while for 2, significant exchange takes place during the time scale of
      the NMR experiment.

PMID- 14709073
TI  - Chemically distinct Ni sites in the A-cluster in subunit beta of the acetyl-CoA
      decarbonylase/synthase complex from Methanosarcina thermophila: Ni L-edge
      absorption and X-ray magnetic circular dichroism analyses.
AB  - The 5-subunit-containing acetyl-CoA decarbonylase/synthase (ACDS) complex plays
      an important role in methanogenic Archaea that convert acetate to methane, by
      catalyzing the central reaction of acetate C-C bond cleavage in which acetyl-CoA
      serves as the acetyl donor substrate reacting at the ACDS beta subunit active
      site. The properties of Ni in the active site A-cluster in the ACDS beta subunit
      from Methanosarcina thermophila were investigated. A recombinant, C-terminally
      truncated form of the beta subunit was employed, which mimics the native subunit
      previously isolated from the ACDS complex, and contains an A-cluster composed of
      an [Fe(4)S(4)] center bridged to a binuclear Ni-Ni site. The electronic
      structures of these two Ni were studied using L-edge absorption and X-ray
      magnetic circular dichroism (XMCD) spectroscopy. The L-edge absorption data
      provided evidence for two distinct Ni species in the as-isolated enzyme, one with
      low-spin Ni(II) and the other with high-spin Ni(II). XMCD spectroscopy confirmed
      that the species producing the high-spin signal was paramagnetic. Upon treatment
      with Ti(3+) citrate, an additional Ni species emerged, which was assigned to
      Ni(I). By contrast, CO treatment of the reduced enzyme converted nearly all of
      the Ni in the sample to low-spin Ni(II). The results implicate reaction of a high
      spin tetrahedral Ni site with CO to form an enzyme-CO adduct transformed to a low
      spin Ni(II) state. These findings are discussed in relation to the mechanism of C
      C bond activation, in connection with the model of the beta subunit A-cluster
      developed from companion Ni and Fe K edge, XANES, and EXAFS studies.

PMID- 14709074
TI  - Enantioselective total synthesis of erogorgiaene: applications of asymmetric Cu
      catalyzed conjugate additions of alkylzincs to acyclic enones.
AB  - The first enantioselective synthesis of erogorgiaene (1), an inhibitor of
      mycobacterium tuberculosis, is disclosed. The total synthesis highlights the
      utility of asymmetric conjugate additions (ACA) of alkylzincs to acyclic
      alpha,beta-unsaturated ketones catalyzed by peptidic phosphine ligands and
      (CuOTf)(2).C(6)H(6). Moreover, several critical attributes of this catalytic C-C
      bond-forming reaction are illustrated in the context of the total synthesis;
      these include the significance of various structural features of the amino acid
      based chiral ligands and the chiral ligand's effectiveness in reactions involving
      achiral and chiral substrates. In addition, the total synthesis showcases some of
      the special properties of nonphosphine Ru complex 3 as a highly effective
      catalyst for olefin cross-metathesis.

PMID- 14709075
TI  - Dynamics of protein and peptide hydration.
AB  - Biological processes often involve the surfaces of proteins, where the structural
      and dynamic properties of the aqueous solvent are modified. Information about the
      dynamics of protein hydration can be obtained by measuring the magnetic
      relaxation dispersion (MRD) of the water (2)H and (17)O nuclei or by recording
      the nuclear Overhauser effect (NOE) between water and protein protons. Here, we
      use the MRD method to study the hydration of the cyclic peptide oxytocin and the
      globular protein BPTI in deeply supercooled solutions. The results provide a
      detailed characterization of water dynamics in the hydration layer at the surface
      of these biomolecules. More than 95% of the water molecules in contact with the
      biomolecular surface are found to be no more than two-fold motionally retarded as
      compared to bulk water. In contrast to small nonpolar molecules, the retardation
      factor for BPTI showed little or no temperature dependence, suggesting that the
      exposed nonpolar residues do not induce clathrate-like hydrophobic hydration
      structures. New NOE data for oxytocin and published NOE data for BPTI were
      analyzed, and a mutually consistent interpretation of MRD and NOE results was
      achieved with the aid of a new theory of intermolecular dipolar relaxation that
      accounts explicitly for the dynamic perturbation at the biomolecular surface. The
      analysis indicates that water-protein NOEs are dominated by long-range dipolar
      couplings to bulk water, unless the monitored protein proton is near a partly or
      fully buried hydration site where the water molecule has a long residence time.

PMID- 14709076
TI  - Hydroxylation by the hydroperoxy-iron species in cytochrome P450 enzymes.
AB  - Intramolecular and intermolecular kinetic isotope effects (KIEs) were determined
      for hydroxylation of the enantiomers of trans-2-(p
      trifluoromethylphenyl)cyclopropylmethane (1) by hepatic cytochrome P450 enzymes,
      P450s 2B1, Delta2B4, Delta2B4 T302A, Delta2E1, and Delta2E1 T303A. Two products
      from oxidation of the methyl group were obtained, unrearranged trans-2-(p
      trifluoromethylphenyl)cyclopropylmethanol (2) and rearranged 1-(p
      trifluoromethylphenyl)but-3-en-1-ol (3). In intramolecular KIE studies with
      dideuteriomethyl substrates (1-d(2)) and in intermolecular KIE studies with
      mixtures of undeuterated (1-d(0)) and trideuteriomethyl (1-d(3)) substrates, the
      apparent KIE for product 2 was consistently larger than the apparent KIE for
      product 3 by a factor of ca. 1.2. Large intramolecular KIEs found with 1-d(2)
      (k(H)/k(D) = 9-11 at 10 degrees C) were shown not to be complicated by tunneling
      effects by variable temperature studies with two P450 enzymes. The results
      require two independent isotope-sensitive processes in the overall hydroxylation
      reactions that are either competitive or sequential. Intermolecular KIEs were
      partially masked in all cases and largely masked for some P450s. The intra- and
      intermolecular KIE results were combined to determine the relative rate constants
      for the unmasking and hydroxylation reactions, and a qualitative correlation was
      found for the unmasking reaction and release of hydrogen peroxide from four of
      the P450 enzymes in the absence of substrate. The results are consistent with the
      two-oxidants model for P450 (Vaz, A. D. N.; McGinnity, D. F.; Coon, M. J. Proc.
      Natl. Acad. Sci. U.S.A. 1998, 95, 3555), which postulates that a hydroperoxy-iron
      species (or a protonated analogue of this species) is a viable electrophilic
      oxidant in addition to the consensus oxidant, iron-oxo.

PMID- 14709077
TI  - Model studies on p-hydroxybenzoate hydroxylase. The catalytic role of Arg-214 and
      Tyr-201 in the hydroxylation step.
AB  - A model C-(4a)-flavinhydroperoxide (FlHOOH) is described that contains the
      tricyclic isoalloxazine moiety, the C-4a-hydroperoxide functionality, and a beta
      hydroxyethyl group to model the effect of the 2'-OH group of the ribityl side
      chain of native FADHOOH. The electronic structures of this reduced flavin
      (H(3)()Fl(red)()), its N1 anion (H(2)()Fl(red)()(-)()), oxidized flavin
      (HFl(ox)()), and FlHOOH have been fully optimized at the B3LYP/ 6-31+G(d,p) level
      of theory. This model C-4a-flavinhydroperoxide is used to describe the transition
      state for the key step in the paradigm aromatic hydroxylase, p-hydroxybenzoate
      hydroxylase (PHBH): the oxidation of p-hydroxybenzoate (p-OHB). The Tyrosine-201
      residue in PHBH is modeled by phenol, and Arginine-214 is modeled by guanidine.
      Electrophilic aromatic substitution proceeds by an S(N)2-like attack of the
      aromatic sextet of p-OHB phenolate anion on the distal oxygen of FlHOOH 3. The
      transition structure for oxygen atom transfer is fully optimized [B3LYP/6
      31+G(d,p)] and has a classical activation barrier of 24.9 kcal/mol. These data
      suggest that the role of the Tyr-201 is to orient the p-OHB substrate and to
      properly align it for the oxygen transfer step. Although the negatively charged
      phenolate oxygen does activate the C-3 carbon of p-OHB phenolate anion toward
      oxidation relative to ortho oxidation of the carboxylate anion, it appears that H
      bonding the Tyr-201 residue to this phenolic oxygen stabilizes both the ground
      state (GS) and the transition state (TS) approximately equally and therefore
      plays only a minor role, if any, in lowering the activation barrier. Complexation
      of p-OHB with guanidine has only a modest effect upon the oxidation barriers.
      When the complex is in the form of a salt-bridge (10a), the barrier is only
      slightly reduced. When the TSs are placed in THF solvent (COSMO) with full
      geometry optimization, salt-bridge TS-A is slightly favored (DeltaDeltaE() = 2.3
      kcal/mol).

PMID- 14709078
TI  - DNA sequence dependent monomer-dimer binding modulation of asymmetric
      benzimidazole derivatives.
AB  - A number of studies indicate that DNA sequences such as AATT and TTAA have
      significantly different physical and interaction properties. To probe these
      interaction differences in detail and determine the influence of charge, we have
      synthesized three bisbenzimidazole derivatives, a diamidine, DB185, and
      monoamidines, DB183 and DB210, that are related to the well-known minor groove
      agent, Hoechst 33258. Footprinting studies with several natural and designed DNA
      fragments indicate that the synthetic compounds bind at AT sequences in the minor
      groove and interact more weakly at sites with TpA steps relative to sites without
      such steps. Circular dichroism spectroscopy also indicates that the compounds
      bind in the DNA minor groove. Surprisingly, Tm studies as a function of ratio
      indicate that the monoamidines bind to TTAA sequences as dimers, whereas the
      diamidine binds as a monomer. Biosensor-surface plasmon resonance (SPR) studies
      allowed us to quantitate the interaction differences in more detail. SPR results
      clearly show that the monoamidine compounds bind to the TTAA sequence in a
      cooperative 2:1 complex but bind as monomers to AATT. The dication binds to both
      sequences in monomer complexes but the binding to AATT is significantly stronger
      than binding to TTAA. Molecular dynamics simulations indicate that the AATT
      sequence has a narrow time-average minor groove width that is a very good
      receptor site for the bisbenzimidazole compounds. The groove in TTAA sequences is
      wider and the width must be reduced to form a favorable monomer complex. The
      monocations thus form cooperative dimers that stack in an antiparallel
      orientation and closely fit the structure of the TTAA minor groove. The amidine
      groups in the dimer are oriented in the 5' direction of the strand to which they
      are closest. Charge repulsion in the dication apparently keeps it from forming
      the dimer. It instead reduces the TTAA groove width, in an induced fit process,
      sufficiently to form a minor groove complex. The dimer-binding mode of DB183 and
      DB210 is a new DNA recognition motif and offers novel design concepts for
      selective targeting of DNA sequences with a wider minor groove, including those
      with TpA steps.

PMID- 14709079
TI  - Unique tautomeric properties of isoguanine.
AB  - The tautomeric properties of isoguanine (also named 2-oxoadenine or 2
      hydroxyadenine) have been studied in the gas phase, in different pure solvents,
      and in the DNA environment using state of the art theoretical methods. Our
      results show that isoguanine constitutes an unique example of how tautomerism can
      be modulated by the environment. Compared to the tautomeric preference in the gas
      phase, both polar solvents and the DNA microenvironment dramatically change the
      intrinsic tautomeric properties of isoguanine. Tautomers which are important in
      physiological conditions are less than 1/10(5) of the total population of
      isoguanine in the gas phase. The impact of the present findings in the
      understanding of spontaneous mutations and in the design of new nucleobases with
      multiple recognition properties is discussed.

PMID- 14709080
TI  - Duplex dissociation of telomere DNAs induced by molecular crowding.
AB  - Because of the importance of telomere DNAs, the structures of these DNAs in vivo
      are currently of great research interest in the medical, pharmaceutical,
      chemical, and industrial fields. To understand the structure of biomolecules in
      vivo, their properties studied in vitro are extrapolated to the in vivo
      condition, while the condition in a living cell is inherently molecularly crowded
      and a nonideal solution contains various biomolecules. We investigated the effect
      of molecular crowding, which is one of the most important cellular environmental
      conditions, on the structure and stability of the telomere and G-rich and C-rich
      DNAs using circular dichroism (CD) spectra, CD melting curves, and isothermal
      titration calorimetry (ITC). The CD spectra and CD melting curves of G-rich DNA,
      C-rich DNA, and the 1:1 mixture of G-rich and C-rich DNAs showed that each G-rich
      DNA, C-rich DNA, and the 1:1 mixture form the antiparallel G-quadruplex, I-motif,
      and duplex, respectively, in the noncrowding condition as previously considered.
      On the contrary, the G-rich and C-rich DNAs individually form the parallel G
      quadruplex and I-motif, respectively, in the molecular crowding condition, and
      the 1:1 mixture folds into the parallel G-quadruplex and I-motif but does not
      form a duplex. The ITC measurements indicated that the thermodynamic stability
      (DeltaG degrees (20)) of the duplex formation between the G-rich and C-rich DNAs
      in the noncrowding condition was -10.2 kcal mol(-)(1), while only a small heat
      change was observed in the ITC measurements in the molecular crowding condition.
      These ITC results also demonstrated that the molecular crowding condition
      prevents any duplex formation between G-rich and C-rich DNAs. These results
      indicate that a structural polymorphism of the telomere DNAs is induced by
      molecular crowding in vivo.

PMID- 14709081
TI  - Polymer brushes on single-walled carbon nanotubes by atom transfer radical
      polymerization of n-butyl methacrylate.
AB  - Polymer brushes with single-walled carbon nanotubes (SWNT) as backbones were
      synthesized by grafting n-butyl methacrylate (nBMA) from the ends and sidewalls
      of SWNT via atom transfer radical polymerization (ATRP). Carboxylic acid groups
      on SWNT were formed by nitric acid oxidation. The ATRP initiators were covalently
      attached to the SWNT by esterification of 2-hydroxyethyl 2'-bromopropionate with
      carboxylic acid groups. Methyl 2-bromopropionate (MBP) was added as free
      initiator during the brush preparation to control growth of the brushes and to
      monitor the polymerization kinetics. Size-exclusion chromatography (SEC) results
      show that the molecular weight of free poly(n-butyl methacrylate) (PnBMA)
      increased linearly with nBMA monomer conversion. PnBMA cleaved from the SWNT
      after high conversion had the same molecular weight as PnBMA produced in
      solution. Thermogravimetric analyses (TGA) show that the amount of PnBMA grown
      from the SWNT increased linearly with the molecular weight of the free PnBMA. The
      most highly PnBMA-functionalized SWNT dissolve in 1,2-dichlorobenzene,
      chloroform, and tetrahydrofuran, and solubility increases with the amount of
      PnBMA bound to SWNT. Near-infrared and Raman spectra indicate that the side walls
      of the SWNT were lightly functionalized by the nitric acid treatment and that the
      degree of functionalization of the SWNT did not change significantly during the
      formation of initiator or during the polymerization. Atomic force microscopy
      (AFM) images show contour lengths of the SWNT brushes on a mica surface from 200
      nm to 2.0 microm and an average height of the backbone of 2-3 nm, indicating that
      the bundles of original SWNT were broken into individual tubes by
      functionalization and polymerization.

PMID- 14709082
TI  - Hexakis(4-iodophenyl)-peri-hexabenzocoronene- a versatile building block for
      highly ordered discotic liquid crystalline materials.
AB  - Hexakis (4-iodophenyl)-peri-hexabenzocoronene (5), a novel functionalizable
      mesogenic building block, was prepared by rational multistep synthesis. Although
      sparingly soluble in common solvents, it can be obtained in pure form and then
      functionalized via Hagihara-Sonogashira coupling to give a series of highly
      ordered columnar liquid crystalline molecules 14a-c. The total synthesis involves
      five 6-fold transformations, all in excellent to near quantitative isolated
      yields. Their thermotropic liquid crystalline behavior was studied by
      differential scanning calorimetry (DSC), polarized optical microscopy (POM) and
      wide-angle X-ray diffraction (WAXD). Compared to the normal alkyl-subsituted
      hexabenzocoronenes (HBCs), 14a-c exhibit more highly ordered columnar mesophases,
      including three-dimensionally ordered superstructures (helical columnar
      mesophase). These could arise from additional intracolumnar pi-pi interactions
      between, and space-filling requirements introduced by, the rigid-rod side groups.
      Atomic force microscopy (AFM) revealed self-assembled bundles of columnar
      aggregates in spin-coated films and isolated several-micron-long nanoribbons
      composed of a defined number of columns in drop cast films.

PMID- 14709083
TI  - Schulzeines A-C, new alpha-glucosidase inhibitors from the marine sponge Penares
      schulzei.
AB  - Three new alpha-glucosidase inhibitors, schulzeines A-C (1-3), were isolated from
      the marine sponge Penares schulzei. Their structures were elucidated by spectral
      analysis and chemical degradations to be the isoquinoline alkaloids, encompassing
      two amino acids, and C(28) fatty acid, the last of which was sulfated. Absolute
      stereochemistry of schulzeines was determined by application of the modified
      Mosher analysis to fragments obtained by chemical degradation. Schulzeines A-C
      inhibit alpha-glucosidase with IC(50) values of 48-170 nM.

PMID- 14709084
TI  - Direct observation of odd-even effect for chiral alkyl alcohols in solution using
      vibrational circular dichroism spectroscopy.
AB  - The odd-even effect of chiral alkyl alcohols, (S)-CH(3)CHOHC(n)()H(2)(n)()(+1) (n
      = 2-8), in solution state has been observed spectroscopically for the first time.
      The vibrational circular dichroism (VCD) bands at 1148 cm(-)(1) exhibit a clear
      odd-even effect. The observed VCD bands of (R)-(-)-2-hexanol correspond well to
      those predicted (population weighted). Density functional theory calculations
      indicate that the most prevalent conformations in solution are the all-trans
      forms. The odd-even effect of the VCD bands is ascribed to the alternating
      terminal methyl motions in the alkyl chains relative to fixed motions near the
      chiral center in the trans conformations. The conformational sensitivity of VCD
      for the chiral alcohols in the solution state may be useful for the design of
      liquid crystals and ligands in the future.

PMID- 14709085
TI  - Origins of enantioselectivity in reductions of ketones on cinchona alkaloid
      modified platinum.
AB  - A model to explain the stereoselectivities of reductions of activated ketones on
      cinchona alkaloid modified platinum is proposed and is supported by calculations
      by density functional and force field methods. The model involves nucleophilic
      catalysis by the cinchona alkaloid. The zwitterionic adduct between a cinchona
      alkaloid and ketone is adsorbed on Pt through the quinoline ring and two
      heteroatoms and is subsequently reduced with inversion. The model rationalizes
      the observed stereoselectivities for hydrogenation of carbonyl compounds.

PMID- 14709086
TI  - Lanthanide-transition-metal carbonyl complexes: new [Co4(CO)11]2- clusters and
      lanthanide(II) isocarbonyl polymeric arrays.
AB  - Two types of Ln(II)-Co(4) isocarbonyl polymeric arrays, [(Et(2)O)(3)(
      )(x)()(THF)(x)()Ln[Co(4)(CO)(11)]]( infinity ) (1-3; x = 0, 1) and
      [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4), were prepared and structurally
      characterized. Transmetalation involving Ln(0) and Hg[Co(CO)(4)](2) in Et(2)O
      yields [(Et(2)O)(3)Ln[Co(4)(CO)(11)]]( infinity ) (1, Ln = Yb; 2, Ln = Eu).
      Dissolution of the solvent-separated ion pairs [Ln(THF)(x)()][Co(CO)(4)](2) (Ln =
      Yb, x = 6; Ln = Eu) in Et(2)O affords [(Et(2)O)(2)(THF)Yb[Co(4)(CO)(11)]](
      infinity ) (3) and [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4). In these
      reactions, oxidation and condensation of the [Co(CO)(4)](-) anions result in
      formation of the new tetrahedral cluster [Co(4)(CO)(11)](2)(-). The two types of
      Ln(II)-Co(4) compounds contain different isomers of [Co(4)(CO)(11)](2)(-), and,
      consequently, the structures of the infinite isocarbonyl networks are distinct.
      The cluster in [(Et(2)O)(3)(-)(x)()(THF)(x)()Ln[Co(4)(CO)(11)]]( infinity ) (1-3)
      possesses pseudo C(3)(v)() symmetry (an apical Co, three basal Co atoms; one face
      bridging, three edge-bridging, seven terminal carbonyls) and connects to Ln(II)
      centers through eta(2),micro(4)- and eta(2),micro(3)-carbonyls to generate a 2-D
      puckered sheet. In contrast, [(THF)(5)Eu[Co(4)(CO)(11)]]( infinity ) (4)
      incorporates a C(2)(v)() symmetric cluster (two unique Co environments; two face
      bridging, one edge-bridging, eight terminal carbonyls), and isocarbonyl linkages
      (eta(2),micro(4)-carbonyls) to Eu(II) atoms create a 1-D zigzag chain. Complexes
      1-4 contain the first reported eta(2),micro(4)-CO bridges between a Ln and a
      transition-metal carbonyl cluster. Infrared spectroscopic studies revealed that
      the isocarbonyl associations to Ln(II) persist in solution. The solution
      structure and dynamic behavior of the [Co(4)(CO)(11)](2)(-) cluster in 1 was
      investigated by variable-temperature (59)Co and (13)C NMR spectroscopies.

PMID- 14709087
TI  - Shape-persistent macrocycles with intraannular polar groups: synthesis, liquid
      crystallinity, and 2D organization.
AB  - The synthesis of macrocycles with intraannular polar ester groups and
      extraannular oligo-alkyl groups is described. The compounds exhibit stable liquid
      crystalline phases showing fan-shaped textures under the polarizing microscope,
      typical for a columnar order of the molecules. X-ray powder diffraction data of
      the LC phase indicate that the unit cell contains two symmetry-related units, a
      feature pointing most probably to a restricted rotation of the macrocycles within
      a stack. The X-ray data were further supported by solid-state NMR experiments,
      showing that the rigid core of the compounds does not rotate with kHz or higher
      frequencies within the column in the LC phase. Apart from the organization of the
      molecules in the LC phase, the 2D organization of the macrocycles at the solvent
      highly oriented pyrolytic graphite (HOPG) interface was investigated and showed
      that these compounds are capable of nanofunctionalizing the HOPG surface in the
      multinanometer regime.

PMID- 14709088
TI  - Ruffling-induced chirality: synthesis, metalation, and optical resolution of
      highly nonplanar, cyclic, benzimidazole-based ligands.
AB  - Expedient five-step syntheses of a cyclic bis(benzimidazole)-based amide 5 and
      two sterically more hindered analogues 23-24 have been developed. These amides
      are chiral due to the inherent ruffling of the macrocyclic plane. Racemization of
      the optical antipodes of these compounds has been studied using dynamic chiral
      stationary phase HPLC. These studies reveal that, while the parent amide 5
      racemizes rapidly, for the sterically more hindered amides 23-24, the rate of
      racemization is significantly reduced. Bis(benzimidazole)-based amides 5 and 23
      24 form stable Ni(II) complexes 25-27, respectively. Like their parent ligands,
      complexes 25-27 are chiral due to their highly ruffled geometry. Studies of these
      complexes by chiral stationary phase HPLC reveal that metalation leads to a much
      lower rate of racemization. Incorporation of a strap can slow racemization even
      further. A series of strapped cyclic amides 54-57, along with their corresponding
      dimers 58-61, have been prepared. The rate of racemization for amides 54-57 is
      strongly dependent on the length of the strap. X-ray single-crystal structure
      analysis of the Ni(II) complex of strapped amide 54 reveals that the
      bis(benzimidazole) core retains its highly ruffled shape, with the two phenyl
      rings of the macrocycle located anti to the strap. Chiral separation of strapped
      ligands 54-57 and their corresponding Ni(II) complexes is shown to be facile by
      chiral stationary phase HPLC.

PMID- 14709089
TI  - The rearrangements of naphthylnitrenes: UV/Vis and IR spectra of azirines, cyclic
      ketenimines, and cyclic nitrile ylides.
AB  - Ar matrix photolysis of 1- and 2-naphthyl azides 3 and 4 at 313 nm initially
      affords the singlet naphthyl nitrenes, (1)()1 and (1)()2. Relaxation to the
      corresponding lower energy, persistent triplet nitrenes (3)()1 and (3)()2
      competes with cyclization to the azirines 15 and 18, which can also be formed
      photochemically from the triplet nitrenes. On prolonged irradiation, the azirines
      can be converted to the seven-membered cyclic ketenimines 10 and 13,
      respectively, as described earlier by Dunkin and Thomson. However, instead of the
      o-quinoid ketenimines 16 and 19, which are the expected primary ring-opening
      products of azirines 15 and 18, respectively, we observed their novel bond-shift
      isomers 17 and 20, which may be formally regarded as cyclic nitrile ylides. The
      existence of such ylidic heterocumulenes has been predicted previously, but this
      work provides the first experimental observation of such species. The factors
      which are responsible for the special stability of the ylidic species 17 and 20
      are discussed.

PMID- 14709090
TI  - Ruthenium-catalyzed Heck-type olefination and Suzuki coupling reactions: studies
      on the nature of catalytic species.
AB  - Ruthenium-catalyzed Heck olefination and Suzuki cross coupling reactions have
      been developed. When starting with a ruthenium complex [RuCl(2)(p-cymene)](2) as
      a homogeneous catalyst precursor, induction periods were observed and ruthenium
      colloids of zero oxidation state were generated under catalytic conditions.
      Isolated ruthenium colloids carried out the olefination, implying that active
      catalytic species are ruthenium nanoclusters. To support this hypothesis,
      ruthenium nanoparticles stabilized with dodecylamine were independently prepared
      via a hydride reduction procedure, and their catalytic activity was subsequently
      examined. Olefination of iodobenzene with ethyl acrylate was efficiently
      catalyzed by the ruthenium nanoparticles under the same conditions, which could
      be also reused for the next runs. In poisoning experiments, the conversion of the
      olefination was completely inhibited in the presence of mercury, thus supporting
      our assumption on the nature of catalytic species. No residual ruthenium was
      detected from the filtrate at the end of the reaction. On the basis of the
      postulation, a heterogeneous catalyst system of ruthenium supported on alumina
      was consequently developed for the Heck olefination and Suzuki cross coupling
      reactions for the first time. It turned out that substrate scope and selectivity
      were significantly improved with the external ligand-free catalyst even under
      milder reaction conditions when compared to results with the homogeneous
      precatalyst. It was also observed that the immobilized ruthenium catalyst was
      recovered and reused up to several runs with consistent efficiency. Especially in
      the Suzuki couplings, the reactions could be efficiently carried out with as low
      as 1 mol % of the supported catalyst over a wide range of substrates and were
      scaled up to a few grams without any practical problems, giving coupled products
      with high purity by a simple workup procedure.

PMID- 14709091
TI  - [Ni0]-catalyzed Co-oligomerization of 1,3-butadiene and ethylene: a theoretical
      mechanistic investigation of competing routes for generation of linear and cyclic
      C10-olefins.
AB  - A detailed theoretical investigation of the mechanism for the [Ni(0)]-catalyzed
      co-oligomerization of 1,3-butadiene and ethylene to afford linear and cyclic
      C(10)-olefins is presented. Crucial elementary processes have been carefully
      explored for a tentative catalytic cycle, employing a gradient-corrected density
      functional theory (DFT) method. The favorable route for oxidative coupling starts
      from the prevalent [Ni(0)(eta(2)-butadiene)(2)(ethylene)] form of the active
      catalyst through oxidative coupling between the two eta(2)-butadienes. The
      initial eta(3),eta(1)(C(1))-octadienediyl-Ni(II) product is the active precursor
      for ethylene insertion, which preferably takes place into the syn-eta(3)-allyl
      Ni(II) bond of the prevalent eta(3)-syn,eta(1)(C(1)),Delta-cis isomer. The
      insertion is driven by a strong thermodynamic force, giving rise entirely to
      eta(3),eta(1),Delta-trans-decatrienyl-Ni(II) forms, with the eta(3)
      anti,eta(1),Delta-trans isomer almost exclusively generated. Occurrence of
      allyl,eta(1),Delta-cis isomers, however, is precluded on both kinetic and
      thermodynamic grounds, thereby rationalizing the observation that cis-DT and
      cis,cis-CDD are never formed. Linear and cyclic C(10)-olefins are generated in a
      highly stereoselective fashion, with trans-DT and cis,trans-CDD as the only
      isomers, along competing routes of stepwise transition-metal-assisted H-transfer
      (DT) and reductive CC elimination under ring closure (CDD), respectively, that
      start from the prevalent eta(3)-anti,eta(1),Delta-trans-decatrienyl-Ni(II)
      species. The role of allylic conversion in the octadienediyl-Ni(II) and
      decatrienyl-Ni(II) complexes has been analyzed. As a result of the detailed
      exploration of all important elementary steps, a theoretically verified, refined
      catalytic cycle is proposed and the regulation of the selectivity for formation
      of linear and cyclic C(10)-olefins is elucidated.

PMID- 14709092
TI  - Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles.
AB  - High-temperature solution phase reaction of iron(III) acetylacetonate,
      Fe(acac)(3), with 1,2-hexadecanediol in the presence of oleic acid and oleylamine
      leads to monodisperse magnetite (Fe(3)O(4)) nanoparticles. Similarly, reaction of
      Fe(acac)(3) and Co(acac)(2) or Mn(acac)(2) with the same diol results in
      monodisperse CoFe(2)O(4) or MnFe(2)O(4) nanoparticles. Particle diameter can be
      tuned from 3 to 20 nm by varying reaction conditions or by seed-mediated growth.
      The as-synthesized iron oxide nanoparticles have a cubic spinel structure as
      characterized by HRTEM, SAED, and XRD. Further, Fe(3)O(4) can be oxidized to
      Fe(2)O(3), as evidenced by XRD, NEXAFS spectroscopy, and SQUID magnetometry. The
      hydrophobic nanoparticles can be transformed into hydrophilic ones by adding
      bipolar surfactants, and aqueous nanoparticle dispersion is readily made. These
      iron oxide nanoparticles and their dispersions in various media have great
      potential in magnetic nanodevice and biomagnetic applications.

PMID- 14709093
TI  - Spectroscopic properties and quantum chemistry-based normal coordinate analysis
      (QCB-NCA) of a dinuclear tantalum complex exhibiting the novel side-on end-on
      bridging geometry of N2: correlations to electronic structure and reactivity.
AB  - The vibrational properties and the electronic structure of the side-on end-on
      N(2)-bridged Ta complex ([NPN]Ta(micro-H))(2)(micro-eta(1):eta(2)-N(2)) (1)
      (where [NPN] = (PhNSiMe(2)CH(2))(2)PPh) are analyzed. Vibrational
      characterization of the Ta(2)(micro-N(2))(micro-H)(2) core is based on resonance
      Raman and infrared spectroscopies evaluated with a novel quantum chemistry-based
      normal coordinate analysis (QCB-NCA). The N-N stretching frequency is found at
      1165 cm(-)(1) exhibiting a (15)N(2) isotope shift of -37 cm(-)(1). Four other
      modes of the Ta(2)N(2)H(2) core are observed between 430 and 660 cm(-)(1). Two
      vibrations of the bridging hydrido ligands are also identified in the spectra. On
      the basis of experimental frequencies and the QCB-NCA procedure, the N-N force
      constant is determined to be 2.430 mdyn A(-)(1). The Ta-N force constants are
      calculated to be 2.517 mdyn A(-)(1) for the Ta-eta(1)-N(2) bond and 1.291 and
      0.917 mdyn A(-)(1) for the Ta-eta(2)-N(2) bonds, respectively. DFT calculations
      on 1 suggest that the bridging dinitrogen ligand carries a charge of -1.1, which
      is equally distributed over the two nitrogen atoms. However, orbital analysis
      reveals that the terminal nitrogen makes lower contributions to the pi orbitals
      and much higher contributions to the pi orbitals of the N(2) ligand than the
      bridging nitrogen. This suggests that reactions of the dinitrogen ligand with
      electrophiles should preferentially occur at the terminal N atom, in agreement
      with experimental results.

PMID- 14709094
TI  - Proton transfer and a dielectric phase transition in the molecular conductor
      (HDABCO+)2(TCNQ)3.
AB  - One-dimensional dielectric (N.H.N)( infinity ) hydrogen-bonding chains of
      monoprotonated 1,4-diazabicyclo[2.2.2]octane (HDABCO(+)) were introduced into an
      electrically conducting 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) salt as the
      countercation structure. Room-temperature electrical conductivity was
      approximately 10(-)(3) S cm(-)(1), with a semiconductive behavior. The
      temperature-dependent dielectric constants of (HDABCO(+))(2)(TCNQ)(3) indicated a
      dielectric transition at 306 K. A large deuterium isotope effect for the
      dielectric transition (DeltaT = 70 K) was observed for the deuterated salt,
      (DDABCO(+))(2)(TCNQ)(3). Thermally activated order/disorder of the protons or
      deuteriums within the one-dimensional hydrogen-bonding chains of (HDABCO(+))(
      infinity ) and (DDABCO(+))( infinity ) affected the dielectric responses in the
      TCNQ-based semiconductors.

PMID- 14709095
TI  - Attenuating negative differential resistance in an electroactive self-assembled
      monolayer-based junction.
AB  - The negative differential resistance (NDR) peak current observed in redox active
      self-assembled monolayer-based molecular junctions has been attenuated by
      controlling the composition of the molecular junction. Two approaches studied
      here include capping the electroactive ferrocenyl groups with beta-cyclodextrin
      and functionalizing the scanning tunneling microscope tip used to probe the self
      assembled monolayer (SAM) with n-alkanethiols of different lengths. These are the
      first examples of systematic modification of the magnitude of the NDR response in
      a molecule-based system.

PMID- 14709096
TI  - Fluorescence resonance energy transfer between quantum dot donors and dye-labeled
      protein acceptors.
AB  - We used luminescent CdSe-ZnS core-shell quantum dots (QDs) as energy donors in
      fluorescent resonance energy transfer (FRET) assays. Engineered maltose binding
      protein (MBP) appended with an oligohistidine tail and labeled with an acceptor
      dye (Cy3) was immobilized on the nanocrystals via a noncovalent self-assembly
      scheme. This configuration allowed accurate control of the donor-acceptor
      separation distance to a range smaller than 100 A and provided a good model
      system to explore FRET phenomena in QD-protein-dye conjugates. This QD-MBP
      conjugate presents two advantages: (1) it permits one to tune the degree of
      spectral overlap between donor and acceptor and (2) provides a unique
      configuration where a single donor can interact with several acceptors
      simultaneously. The FRET signal was measured for these complexes as a function of
      both degree of spectral overlap and fraction of dye-labeled proteins in the QD
      conjugate. Data showed that substantial acceptor signals were measured upon
      conjugate formation, indicating efficient nonradiative exciton transfer between
      QD donors and dye-labeled protein acceptors. FRET efficiency can be controlled
      either by tuning the QD photoemission or by adjusting the number of dye-labeled
      proteins immobilized on the QD center. Results showed a clear dependence of the
      efficiency on the spectral overlap between the QD donor and dye acceptor.
      Apparent donor-acceptor distances were determined from efficiency measurements
      and corresponding Forster distances, and these results agreed with QD
      bioconjugate dimensions extracted from structural data and core size variations
      among QD populations.

PMID- 14709097
TI  - A comparative study of claisen and cope rearrangements catalyzed by chorismate
      mutase. An insight into enzymatic efficiency: transition state stabilization or
      substrate preorganization?
AB  - In this work we present a detailed analysis of the activation free energies and
      averaged interactions for the Claisen and Cope rearrangements of chorismate and
      carbachorismate catalyzed by Bacillus subtilischorismate mutase (BsCM) using
      quantum mechanics/molecular mechanics (QM/MM) simulation methods. In gas phase,
      both reactions are described as concerted processes, with the activation free
      energy for carbachorismate being about 10-15 kcal mol(-)(1) larger than for
      chorismate, at the AM1 and B3LYP/6-31G levels. Aqueous solution and BsCM active
      site environments reduce the free energy barriers for both reactions, due to the
      fact that in these media the two carboxylate groups can be approached more easily
      than in the gas phase. The enzyme specifically reduces the activation free energy
      of the Claisen rearrangement about 3 kcal mol(-)(1) more than that for the Cope
      reaction. This result is due to a larger transition state stabilization
      associated to the formation of a hydrogen bond between Arg90 and the ether
      oxygen. When this oxygen atom is changed by a methylene group, the interaction is
      lost and Arg90 moves inside the active site establishing stronger interactions
      with one of the carboxylate groups. This fact yields a more intense rearrangement
      of the substrate structure. Comparing two reactions in the same enzyme, we have
      been able to obtain conclusions about the relative magnitude of the substrate
      preorganization and transition state stabilization effects. Transition state
      stabilization seems to be the dominant effect in this case.

PMID- 14709098
TI  - Rhodium-catalyzed methylenation of aldehydes.
AB  - The rhodium-catalyzed methylenation of aldehydes using trimethylsilyldiazomethane
      and triphenylphosphine produces a variety of terminal alkenes in excellent
      yields. These mild and nonbasic reaction conditions allow the conversion of
      enolizable substrates (keto aldehydes and nonracemic alpha-substituted aldehydes)
      to terminal alkenes without epimerization. Optimization of the reaction
      conditions led to the conclusion that a variety of rhodium(I) sources can be used
      as catalysts. The effect of the solvent on the reaction has also been studied,
      and it indicates that although the THF is the best solvent, other solvents may be
      used. The reactivity of the system is very much dependent on the nature of the
      phosphine reagent. The use of an easily removable phosphine is also described.
      Spectroscopic studies indicate that the reaction proceeds via an unusual
      mechanism which leads to the in situ formation of the salt-free phosphorus ylide,
      methylenetriphenylphosphorane.

PMID- 14709099
TI  - Highly active trialkoxymolybdenum(VI) alkylidyne catalysts synthesized by a
      reductive recycle strategy.
AB  - A systematic study of alkyne metathesis catalyzed by trialkoxymolybdenum(VI)
      alkylidyne complexes is reported, in which substrate functional groups, alkynyl
      substituents, and catalyst ligands are varied. Sterically hindered
      trisamidomolybdenum(VI) propylidyne complex 5 was prepared conveniently through a
      previously communicated reductive recycle strategy. Alcoholysis of 5 with various
      phenols/alcohols provides a set of active catalysts for alkyne metathesis at room
      temperature, among which the catalyst with p-nitrophenol as ligand shows the
      highest catalytic activity and is compatible with a variety of functional groups
      and solvents. A key finding that enabled the use of highly active molybdenum(VI)
      catalysts is replacement of the commonly used propynyl substituents on the
      starting alkyne substrates with butynyl groups. Under reduced pressure using
      1,2,4-trichlorobenzene as an involatile solvent, the alkyne metathesis of butynyl
      substituted compounds proceeds well at 30 degrees C providing high yields (83%
      97%) of dimers. Rationalization of the special role played by butynyl substrates
      is discussed.

PMID- 14709101
TI  - Ab initio molecular dynamics study of formate ion hydration.
AB  - We perform ab initio molecular dynamics simulations of the aqueous formate ion.
      The mean number of water molecules in the first solvation shell, or the hydration
      number, of each formate oxygen is found to be consistent with recent experiments.
      Our ab initio pair correlation functions, however, differ significantly from many
      classical force field results and hybrid quantum mechanics/molecular mechanics
      predictions. They yield roughly one less hydrogen bond between each formate
      oxygen and water than force field or hybrid methods predict. Both the BLYP and
      PW91 exchange correlation functionals give qualitatively similar results. The
      time dependence of the hydration numbers are examined, and Wannier function
      techniques are used to analyze electronic configurations along the molecular
      dynamics trajectory.

PMID- 14709102
TI  - Mechanism of homogeneous Ir(III) catalyzed regioselective arylation of olefins.
AB  - The mechanism of hydroarylation of olefins by a homogeneous Ph-Ir(acac)(2)(L)
      catalyst is elucidated by first principles quantum mechanical methods (DFT), with
      particular emphasis on activation of the catalyst, catalytic cycle, and
      interpretation of experimental observations. On the basis of this mechanism, we
      suggest new catalysts expected to have improved activity. Initiation of the
      catalyst from the inert trans-form into the active cis-form occurs through a
      dissociative pathway with a calculated DeltaH(0 K)() = 35.1 kcal/mol and
      DeltaG(298 K)() = 26.1 kcal/mol. The catalytic cycle features two key steps, 1,2
      olefin insertion and C-H activation via a novel mechanism, oxidative hydrogen
      migration. The olefin insertion is found to be rate determining, with a
      calculated DeltaH(0 K)() = 27.0 kcal/mol and DeltaG(298 K)() = 29.3 kcal/mol. The
      activation energy increases with increased electron density on the coordinating
      olefin, as well as increased electron-donating character in the ligand system.
      The regioselectivity is shown to depend on the electronic and steric
      characteristics of the olefin, with steric bulk and electron withdrawing
      character favoring linear product formation. Activation of the C-H bond occurs in
      a concerted fashion through a novel transition structure best described as an
      oxidative hydrogen migration. The character of the transition structure is seven
      coordinate Ir(V), with a full bond formed between the migrating hydrogen and
      iridium. Several experimental observations are investigated and explained: (a)
      The nature of L influences the rate of the reaction through a ground-state
      effect. (b) The lack of beta-hydride products is due to kinetic factors, although
      beta-hydride elimination is calculated to be facile, all further reactions are
      kinetically inaccessible. (c) Inhibition by excess olefin is caused by
      competitive binding of olefin and aryl starting materials during the catalytic
      cycle in a statistical fashion. On the basis of this insertion-oxidative hydrogen
      transfer mechanism we suggest that electron-withdrawing substituents on the acac
      ligands, such as trifluoromethyl groups, are good modifications for catalysts
      with higher activity.

PMID- 14709100
TI  - Energy migration in novel pH-triggered self-assembled beta-sheet ribbons.
AB  - Energy migration between tryptophan residues has been experimentally demonstrated
      in self-assembled peptide tapes. Each peptide contains 11 amino acids with a Trp
      at position 6. The peptide self-assembly is pH-sensitive and forms amphiphilic
      tapes, which further stack in ribbons (double tapes) and fibrils in water
      depending on the concentration. Fluorescence spectra, quenching, and anisotropy
      experiments showed that when the pH is lowered from 9 to 2, the peptide self
      assembly buries the tryptophan in a hydrophobic and restricted environment in the
      interior of stable ribbons as expected on the basis of the peptide design. These
      fluorescence data support directly and for the first time the presence of such
      ribbons which are characterized by a highly packed and stable hydrophobic
      interior. In common with Trp in many proteins, fluorescence lifetimes are
      nonexponential, but the average lifetime is shorter at low pH, possibly due to
      quenching with neighboring Phe residues. Unexpectedly, time-resolved fluorescence
      anisotropy does not change significantly with self-assembly when in water. In
      highly viscous sucrose-water mixtures, the anisotropy decay at low pH was largely
      unchanged compared to that in water, whereas at high pH, the anisotropy decay
      increased significantly. We concluded that depolarization at low pH was not due
      to rotational diffusion but mainly due to energy migration between adjacent
      tryptophan residues. This was supported by a master equation kinetic model of Trp
      Trp energy migration, which showed that the simulated and experimental results
      are in good agreement, although on average only three Trp residues were visited
      before emission.

PMID- 14709103
TI  - Quantum chemical study on the configurations of encapsulated metal ions and the
      molecular vibration modes in endohedral dimetallofullerene La2@C80.
AB  - The configuration of La ions of La(2)@C(80) in the [80]fullerene cage was
      investigated by use of quantum chemical calculations. We found that the D(3)(d)()
      configuration is the global minimum in total energy, being more stable by 1.9
      kcal/mol than the D(2)(h)() configuration, which has been considered to be the
      most stable. The potential energy surface calculation clarified that La ions
      travel between 10 equivalent D(3)(d)() positions through D(2)(h)() positions and
      consequently form pentagonal dodecahedral trajectory, which is in good agreement
      with the previous synchrotron radiation structural study. The experimental and
      theoretical investigation of the Raman spectrum revealed that the symmetry of
      molecular vibration is dramatically reduced simply by encapsulation of two La
      ions, and resulting vibrational modes were successfully assigned. The Raman peak
      at 163 cm(-)(1) was interpreted as the in-phase synchronously coupled mode of the
      [80]fullerene cage elongation and the La-La stretching, rather than a
      conventional and naive assignment as a metal-to-cage vibration mode.

PMID- 14709104
TI  - Direct covalent grafting of conjugated molecules onto Si, GaAs, and Pd surfaces
      from aryldiazonium salts.
AB  - Using aryldiazonium salts that are air-stable and easily synthesized, we describe
      here a one-step, room-temperature route to direct covalent bonds between pi
      conjugated organic molecules on three material surfaces: Si, GaAs, and Pd. The Si
      can be in the form of single crystal Si including heavily doped p-type Si,
      intrinsic Si, heavily doped n-type Si, on Si(111) and Si(100), and on n-type
      polycrystalline Si. The formation of the aryl-metal or aryl-semiconductor bond
      attachments was confirmed by corroborating evidence from ellipsometry,
      reflectance FTIR, XPS, cyclic voltammetry, and AFM analyses of the surface
      grafted monolayers. A data-encompassing explanation for the mechanism suggests a
      diazonium activation by reduction at the open circuit potential, with aryl
      radical secondary products bonding to the surface. The synthetic details are
      included for preparing the surface-grafted monolayers and the precursor diazonium
      salts. This spontaneous diazonium activation reaction offers an attractive route
      to highly passivating, robust monolayers and multilayers on many surfaces that
      allow for strong bonds between carbon and surface atoms with molecular species
      that are near perpendicular to the surface.

PMID- 14709105
TI  - 15N Chemical shielding in glycyl tripeptides: measurement by solid-state NMR and
      correlation with X-ray structure.
AB  - 15N chemical shielding parameters are reported for central glycyl residues in
      crystallographically characterized tripeptides with alpha-helix, beta-strand,
      polyglycine II (3(1)-helix), and extended structures. Accurate values of the
      shielding components (2-5 ppm) are determined from MAS and stationary spectra of
      peptides containing [2-(13)C,(15)N]Gly. Two dipolar couplings, (1)H-(15)N and
      (13)C(alpha)-(15)N, are used to examine (15)N shielding tensor orientations in
      the molecular frame and the results indicate that the delta(11), delta(33) plane
      of the shielding tensor is not coincident with the peptide plane. The observed
      isotropic shifts, which vary over a range of 13 ppm, depend on hydrogen bonding
      (direct and indirect) and local conformation. Tensor spans, delta(span) =
      delta(11) - delta(33), and their deviations from axial symmetry, delta(dev) =
      delta(22) - delta(33), vary over a larger range and are grouped according to 2
      degrees structure. Augmented by previously reported (13)C(alpha) shielding
      parameters, a prediction scheme for the 2 degrees structure of glycyl residues in
      proteins based on shielding parameters is proposed.

PMID- 14709106
TI  - The role of intermolecular and molecule-substrate interactions in the stability
      of alkanethiol nonsaturated phases on Au(111).
AB  - The structure and stability of alkanethiols self-assembled on Au(111) have been
      studied as a function of the molecular chain length by means of atomic force
      microscopy (AFM) and grazing incidence X-ray diffraction (GIXD). Below
      saturation, phases consisting of molecules with different tilt angles and
      periodicities are formed. Differences in the mechanical stability of these phases
      are revealed by AFM experiments and discussed in terms of the competition between
      intermolecular and molecule-substrate interactions as a function of chain length.
      For long molecules, intermolecular interactions play a dominant role which
      stabilizes the formation of closed packed 30 degrees tilted ( radical 3x radical
      3)R30 degrees structures. For short molecules, the van der Waals interaction with
      the gold substrate favors the formation of a 50 degrees tilted phase in which the
      molecules are arranged in a rectangular configuration.

PMID- 14709107
TI  - An approach to developing a force field for molecular simulation of martensitic
      phase transitions between phases with subtle differences in energy and structure.
AB  - d,l-Norleucine is one of only a few molecules whose crystals exhibit a
      martensitic or displacive-type phase transformation where the emerging phase
      shows a topotaxial relationship with the parent phase. The molecular mechanism
      for such phase transformations, particularly in molecular crystals, is not well
      understood. Crystalline phases that exhibit displacive phase transitions tend to
      be very similar in structure and energy. Consequently, the development of a force
      field for such phases is challenging as the phase behavior is determined by
      subtle differences in their lattice energies and entropies. We report an approach
      for developing a force field for such phases with an application to d,l
      norleucine. The proposed procedure includes calculation of the phase diagram of
      the crystalline phases as a function of temperature to identify the best force
      field. d,l-Norleucine also presents an additional problem since in the solid
      state it exists as a zwitterion that is unstable in vacuo and therefore cannot be
      characterized using high-level ab initio calculations in the gas phase. However,
      a stable zwitterion could be obtained using Onsager's reaction-field continuum
      model for a solvent (SCRF) using both Hartree-Fock and density functional theory.
      A number of force fields and the various sets of partial charges obtained from
      the SCRF calculations were screened for their ability to reproduce the crystal
      structures of the two known phases, alpha and beta, of d,l-norleucine. Selected
      parameter sets were then employed in free energy minimizations to identify the
      best set on the basis of a correct prediction of the alpha-beta phase transition.
      The Williams' nonbonded parameters combined with partial charges from SCRF
      Polarized Continuum Model calculation were found to reproduce the structures of
      the phases accurately and also maintained their stability in extended molecular
      dynamics simulations in the Parrinello-Rahman constant stress ensemble. Moreover,
      we were also able to successfully simulate the phase transformation of the beta-
      to the alpha-phase. The identified force field should enable detailed studies of
      the phase transformations exhibited by crystals of d,l-norleucine and hence
      enhance our understanding of martensitic-type transformations in molecular
      crystals.

PMID- 14709111
TI  - Sources of variability and systematic error in mouse timing behavior.
AB  - In the peak procedure, starts and stops in responding bracket the target time at
      which food is expected. The variability in start and stop times is proportional
      to the target time (scalar variability), as is the systematic error in the mean
      center (scalar error). The authors investigated the source of the error and the
      variability, using head poking in the mouse, with target intervals of 5 s, 15 s,
      and 45 s, in the standard procedure, and in a variant with 3 different target
      intervals at 3 different locations in a single trial. The authors conclude that
      the systematic error is due to the asymmetric location of start and stop decision
      criteria, and the scalar variability derives primarily from sources other than
      memory.

PMID- 14709112
TI  - Pavlovian conditioning: the CS-UR relation.
AB  - A new Pavlovian procedure used fluid-elicited throat-movement responses of the
      pigeon (N=66) to study the effects on conditioning of the temporal relation of
      the conditioned stimulus (CS) to the unconditioned stimulus-unconditioned
      response (US-UR). Because the throat-movement response has a substantial latency
      and duration, the relation of the CS to the US and UR could be independently
      evaluated. Four experiments indicated that, operationally, the relation of the CS
      to the UR--not to the US--is critical for conditioning in this preparation. The
      conventional emphasis on CS-US relations is based on procedures that confound the
      occurrence of the US with the UR and that foster generalization decrement between
      training and testing. The authors indicate how several conditioning phenomena may
      be reinterpreted in terms of CS-UR relations.

PMID- 14709113
TI  - Absence of an interaction between navigational strategies based on local and
      distal landmarks.
AB  - In 3 experiments, rats were required to escape from a Morris pool by swimming to
      a submerged platform that was located at the apex of a notional, equilateral
      triangle with 2 different landmarks occupying the corners at the base. Training
      for 1 group was always conducted in view of the landmarks surrounding the pool
      and with the triangular array in a fixed orientation. Subjects could therefore
      identify the direction of the platform from a single landmark within the pool by
      reference to cues outside the pool or to the other landmark within the pool. Both
      strategies were used, and the results from additional groups revealed that the
      first of these strategies did not affect the acquisition of the second one.

PMID- 14709114
TI  - Immediacy versus anticipated delay in the time-left experiment: a test of the
      cognitive hypothesis.
AB  - In the time-left experiment (J. Gibbon & R. M. Church, 1981), animals are said to
      compare an expectation of a fixed delay to food, for one choice, with a
      decreasing delay expectation for the other, mentally representing both upcoming
      time to food and the difference between current time and upcoming time (the
      cognitive hypothesis). The results of 2 experiments support a simpler view: that
      animals choose according to the immediacies of reinforcement for each response at
      a time signaled by available time markers (the temporal control hypothesis). It
      is not necessary to assume that animals can either represent or subtract
      representations of times to food to explain the results of the time-left
      experiment.

PMID- 14709115
TI  - The US-preexposure effect in lithium-induced flavor-aversion conditioning is a
      consequence of blocking by injection cues.
AB  - In 2 experiments, rats received flavor-aversion conditioning in which the
      unconditioned stimulus (US) was an orally consumed solution of lithium chloride
      (LiCl). The resulting aversion was not attenuated by giving preexposure to
      injections of LiCl, although such preexposure did attenuate aversions established
      using injected LiCl as the US (Experiment 1). This outcome suggests that blocking
      by injection-related cues is responsible for the US-preexposure effect observed
      in this situation. Experiment 2 confirmed this interpretation by showing that
      presenting such cues (by giving an injection of saline) at the time that the LiCl
      was drunk resulted in an attenuation of conditioning in animals preexposed to
      injections of LiCl. The US-preexposure effect obtained in these experiments can
      be explained solely in terms of blocking by injection cues, although other
      mechanisms may contribute to the effect seen in other flavor-aversion paradigms.

PMID- 14709116
TI  - Associative history affects the associative change undergone by both presented
      and absent cues in human causal learning.
AB  - R. A. Rescorla (2000) noted that a number of influential theories of associative
      learning do not take the associative history of cues (i.e., the prior training
      that they have received) into account when calculating the associative change
      undergone by those cues. The authors tested this assumption in a human causal
      learning paradigm and found associative history to be an important determinant of
      the learning undergone by cues that are presented on a trial. Moreover,
      associative history was also found to influence the amount of retrospective
      revaluation undergone by absent cues. These findings conflict with models of
      causal learning in which the associative change undergone by an element of a cue
      compound is governed by a summed error term (e.g., R. A. Rescorla & A. R. Wagner,
      1972).

PMID- 14709117
TI  - Choice with initial and terminal link reinforcement: an alternative self-control
      paradigm.
AB  - Self-control is demonstrated when a less desirable immediate outcome is chosen to
      ensure a substantially better future. In a novel animal analogue of this
      situation, primary reinforcement was delivered in both the initial and terminal
      links of a concurrent chain schedule. Rats made initial link choices between
      equal amounts of ethanol-free or ethanol-containing milk. Choosing the ethanol
      free reinforcer resulted in delivery of the larger terminal link reinforcer and
      was thus analogous to self-control. Self-control decreased as the delay between
      initial and terminal links increased. The results have implications for human
      choice situations where decisions are made between two immediately available
      reinforcement alternatives each associated with a different delayed outcome.

PMID- 14709118
TI  - New Zealand's Health Practitioners Competence Assurance Act.

PMID- 14709119
TI  - Antivenom efficacy, safety and availability: measuring smoke.
AB  - Improving safety is important, but in many regions antivenoms are not available.

PMID- 14709120
TI  - Designing the health workforce for the 21st century.

PMID- 14709121
TI  - Prevalence of skin screening by general practitioners in regional Queensland.
AB  - OBJECTIVE: To establish the prevalence and predictors of skin screening by
      general practitioners in regional Queensland. DESIGN: Questionnaire administered
      to participants by professional interviewers via telephone. PARTICIPANTS AND
      SETTING: Participants were 3100 adults aged > or = 30 years (66.9% overall
      response rate), selected from residents of 18 regional Queensland communities
      with populations of between 2000 and 10 000 (as recorded in the 1996 Australian
      census). Within the last 10 communities surveyed, an additional telephone survey
      of 727 participants evaluated mole density. The survey was conducted between
      January and October 1998. MAIN OUTCOME MEASURE: Prevalence of whole-body skin
      examinations by GPs. RESULTS: 11% of participants reported a whole-body skin
      examination by a GP during the previous 12 months, and 20% during the previous 3
      years. Men and women reported a similar prevalence of whole-body skin
      examinations. Factors associated with a significantly increased likelihood of
      having had a whole-body skin examination within the previous 3 years included a
      positive attitude towards skin screening, a personal history of non-melanoma skin
      cancer, a tendency to burn, and having more than four moles on the right upper
      arm. CONCLUSIONS: A substantial proportion of Queenslanders undergo skin
      screening. Those at highest risk for skin cancer are more likely to be screened.

PMID- 14709122
TI  - Factors influencing the number needed to excise: excision rates of pigmented
      lesions by general practitioners.
AB  - OBJECTIVE: To identify doctor and patient characteristics associated with
      excision of benign versus malignant pigmented skin lesions. DESIGN, SETTING AND
      PARTICIPANTS: Retrospective audit of data on 4741 pigmented skin lesions excised
      from November 1998 to February 2000 by 468 general practitioners (39% response
      rate) from 223 practices in Perth, WA. (The data used were from the baseline
      period of a randomised controlled trial of a diagnostic aid for pigmented skin
      lesions.) MAIN OUTCOME MEASURE: The number needed to treat (NNT), defined as the
      number of pigmented lesions needed to be excised to identify one melanoma, in
      relation to demographic characteristics of GPs and patients. RESULTS: Relatively
      more benign lesions were excised per melanoma (NNT = 83) in the youngest patients
      (aged 10-19 years) compared with the oldest (aged > or = 70) (NNT = 11) (P
      [trend] < 0.001), in females (NNT = 37) compared with males (NNT = 23) (P =
      0.02), and in the most socioeconomically disadvantaged (NNT = 60) compared with
      the least disadvantaged group (NNT = 20) (P [trend] < 0.001). The most recently
      graduated GPs excised more benign lesions for each melanoma (NNT = 59) than the
      least recently graduated (NNT = 22) (P [trend] = 0.01). CONCLUSIONS: GPs could
      raise their threshold for excising pigmented lesions in patients who are young,
      female, or from areas of low socioeconomic status, or if the GPs themselves are
      recent graduates.

PMID- 14709123
TI  - Parallel infusion of hydrocortisone +/- chlorpheniramine bolus injection to
      prevent acute adverse reactions to antivenom for snakebites.
AB  - OBJECTIVE: To investigate the efficacy of continuous infusion of hydrocortisone
      with or without chlorpheniramine bolus against early adverse reactions to
      polyspecific antivenom. DESIGN AND SETTING: Prospective, double-blind,
      randomised, placebo-controlled trial at General Hospital, Anuradhapura, Sri
      Lanka. SUBJECTS: 52 patients with snake envenoming were randomised to receive
      infusion of hydrocortisone (Group A), hydrocortisone with chlorpheniramine bolus
      (Group B) or placebo (Group C) during the administration of antivenom.
      INTERVENTION: Hydrocortisone 1000 mg in 300 mL of normal saline infusion was
      started 5 min before and continued for 30 min after antivenom. Chlorpheniramine
      10 mg intravenous bolus dose was given 5 min after commencement of antivenom.
      MAIN OUTCOME MEASURES: Occurrence and severity of adverse reactions to antivenom.
      RESULTS: Adverse reactions were observed in 80% (12/15) of Group A, 52% (11/21)
      of Group B, and 81% (13/16) of Group C. Reactions were mild or moderate except in
      two patients. A significant reduction in the number of adverse reactions was seen
      in Group B compared with the placebo group (difference, 29 percentage points; 95%
      CI, 0.2 to 58 percentage points). There was no significant difference between
      Group A and the placebo group. CONCLUSION: Prophylaxis with a parallel
      hydrocortisone infusion alone is ineffective in reducing the occurrence of acute
      adverse reaction to antivenom serum, but combining it with chlorpheniramine seems
      efficacious.

PMID- 14709124
TI  - An outbreak of Plasmodium vivax malaria in Far North Queensland, 2002.
AB  - OBJECTIVE: To describe an outbreak of Plasmodium vivax malaria in Far North
      Queensland in 2002. DESIGN: Epidemiological and entomological investigations;
      molecular analyses of the infecting parasites. MAIN OUTCOME MEASURES: Case
      characteristics, adult and larval mosquito counts at the outbreak location,
      haplotyping of parasites in blood samples from different cases determined through
      sequencing of AMA1 and MSP1 genes. RESULTS: A man with imported P. vivax malaria
      stayed at a camping ground 95 km north of Cairns in late September 2002. This led
      to an outbreak of P. vivax malaria in 10 adults who stayed at the camping ground
      in October. Large numbers of Anopheles farauti sensu lato larvae were present in
      stagnant pools in a creek at the camping ground, and many adult mosquitoes were
      collected nearby. Not only had most of the infected patients been exposed to
      mosquitoes at night, they were also less likely than other campers to have used
      insect repellents appropriately (odds ratio, 0.01; P < 0.001). Two different
      haplotypes of P. vivax, only one of which was detected in the imported case, were
      involved in the outbreak. CONCLUSIONS: Although local transmission of malaria is
      rare in Far North Queensland, the risk is probably higher in the dry season
      (September to December). Campers need to be aware of the increased risk of
      mosquito-borne diseases. Sexual recombination of multiple gametocytes in
      mosquitoes infected by the imported case may have resulted in the two haplotypes
      of P. vivax involved in the outbreak.

PMID- 14709125
TI  - Fatal leptospirosis presenting as musculoskeletal chest pain.
AB  - After holidaying in Vanuatu, a 24-year-old man presented with pleuritic chest
      pain and chest wall tenderness thought to be musculoskeletal in origin. He
      developed fatal acute renal failure, jaundice, respiratory failure, myocarditis
      and rhabdomyolysis. Subsequent serological results showed a rise in serum titre
      of antibodies to Leptospira grippotyphosa, from 1 : 50 to 1 : 800, consistent
      with acute infection.

PMID- 14709126
TI  - Travel insurance and medical evacuation: view from the far side.
AB  - Travel insurers and medical evacuation companies have a responsibility to provide
      an efficient high-quality service to their clients. These companies often deliver
      a standard far short of best practice and far short of their promotional
      brochures. Their services are overdue for governmental review and a lifting of
      standards. Travellers must be given realistic advice about the risks of foreign
      travel and that healthcare resources at their destination may be very limited.
      Travellers must check with their insurer that the policy they buy truly meets
      their needs. Some people should not travel overseas.

PMID- 14709127
TI  - SunSmart Plus": the more informed use of sunscreens.
AB  - The sun protection factor (SPF) of sunscreens is determined by a testing protocol
      that specifies a sunscreen application rate of 2 mg/cm(2) on the skin. Most
      people, for cosmetic and economic reasons, only apply enough sunscreen to achieve
      an SPF of about a third or even a quarter of the level stated on the product. To
      increase public awareness of the problem, manufacturers could be required to
      state both a "tested SPF" and an "expected SPF" (a third of the tested SPF) on
      product labelling. The "SunSmart" message could be modified to make the public
      more aware of the actual protection level they are achieving with sunscreen.
      Other aspects of the SunSmart message (eg, sun avoidance, wearing protective
      clothing) should also be reinforced.

PMID- 14709128
TI  - An unusual cause of an epidural abscess.
AB  - A previously well 30-year-old man presented with severe progressive back pain,
      joint pain and fever. Magnetic resonance imaging confirmed an epidural abscess. A
      sexual history revealed both risk factors for and previous symptoms of a sexually
      acquired infection. Neisseria gonorrhoeae was isolated from a rectal swab and
      from a wrist aspirate, consistent with disseminated gonococcal infection. The
      epidural abscess resolved clinically and radiologically after treatment for N.
      gonorrhoeae with ceftriaxone.

PMID- 14709129
TI  - Mobile telephone use among Melbourne drivers: a preventable exposure to injury
      risk.

PMID- 14709130
TI  - Control of genital chlamydial infection in the Kimberley region of Western
      Australia.

PMID- 14709131
TI  - Positive Q fever skin test after vaccination.

PMID- 14709132
TI  - Reuse of single-use medical devices: how often does this still occur in
      Australia?

PMID- 14709134
TI  - The public hospital of the future.

PMID- 14709135
TI  - Australian healthcare reform: in need of political courage and champions.

PMID- 14709139
TI  - The intergenerational effects of fetal programming: non-genomic mechanisms for
      the inheritance of low birth weight and cardiovascular risk.
AB  - Many epidemiological studies in diverse populations have demonstrated a link
      between low birth weight and subsequent disease. This evidence has given rise to
      the fetal origins hypothesis, which suggests that exposure of the fetus to an
      adverse environment in utero leads to permanent programming of tIssue function
      and a risk of cardiovascular disease. An alternative hypothesis is that low birth
      weight and adult cardiovascular disease are independent features of a genetic
      predisposition to cardiovascular disease. This review describes evidence that the
      programming phenomenon may not be limited to the first generation offspring.
      Results of human and animal studies identify intergenerational programmed effects
      on both birth weight and cardiovascular disease. This may represent a mechanism
      for the non-genetic inheritance of a predisposition to low birth weight and
      adverse cardiovascular risk across a number of generations.

PMID- 14709140
TI  - C-type natriuretic peptide in reproduction, pregnancy and fetal development.
AB  - C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that
      consists of three structurally related peptides with a 17-amino acid ring linked
      by a disulfide bond. In contrast to atrial and brain natriuretic peptides that
      are mainly cardiovascular hormones, CNP acts predominantly in an
      autocrine/paracrine fashion, is commonly considered to be an endothelial hormone
      with antimitogenic properties, and is characterized as a regulator of
      endochondral ossification. Its biological effects are mediated by an
      intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B
      (GC-B) activation. There is growing evidence that this peptide is also involved
      in various reproductive processes as well as in embryonic and fetal development.
      In rodents, CNP and its receptor are highly expressed in the uterus and ovaries
      with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is
      detectable in mice embryos and shows an organ-specific expression in maternal
      reproductive tIssues with the highest concentration in the placenta. This could
      indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation
      e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans,
      besides a postulated fetal de novo synthesis of CNP, both the peptide and its
      receptor are expressed in the placenta and myometrium with opposite regulation of
      CNP in pregnancies complicated by pre-eclampsia or intrauterine growth
      retardation. Since the maternal plasma levels do not reflect these alterations,
      one can conclude that this part of the natriuretic peptide system acts locally
      suggesting that CNP-stimulated cGMP release exhibits organ-specific effects.
      Importantly, CNP has also become a peptide with a distinct role in male
      reproductive processes, since endocrine function of the testis and the regulation
      of penile erection are regulated by the CNP/GC-B axis. This review gives a
      comprehensive overview of the multiple functions of CNP in reproduction and
      pregnancy as well as in embryonic and fetal development.

PMID- 14709141
TI  - cAMP inhibits natriuretic peptide receptor-B activity and increases C-type
      natriuretic peptide in FRTL-5 rat thyroid cells.
AB  - C-type natriuretic peptide (CNP) and its cognate guanylyl cyclase receptor, the
      natriuretic peptide receptor B (NPR-B) together constitute a regulatory system
      that controls cell function via the generation of intracellular cyclic GMP. In
      this report we have examined the role of cAMP signaling in the regulation of CNP
      and NPR-B activity in the FRTL-5 rat thyroid follicular cell line. As had been
      observed earlier with TSH, the cAMP mimetic, dibutyryl cAMP (dbcAMP; 1 mM)
      induced a significant reduction in CNP-stimulated cGMP generation that was first
      apparent after 6 h of treatment. The inhibitory effect of dbcAMP on NPR-B was
      dose dependent, with an EC50 of 0.2 mM. Pretreatment of FRTL-5 cells with either
      of two protein kinase A (PKA) inhibitors, KT-5720 and H-89, failed to curtail the
      dbcAMP reduction in NPR-B activity, suggesting that the cAMP pathway leading to
      inhibition of NPR-B is PKA independent. Whereas either a 30-min or a 24-h
      treatment with the protein kinase C-activator phorbol myristate acetate failed to
      alter maximal levels of CNP-stimulated cGMP, a 24-h exposure to the calcium
      ionophore A23187 reduced CNP-stimulated cGMP to about one-third of control.
      Pretreatment of FRTL-5 cells with the cell-permeable calcium chelator 1,2 bis(2
      aminophenoxy)ethane-N,N,N1,N1-tetraacetic acid, tetraacetoxymethyl ester
      completely abrogated the cAMP-induced reduction of CNP-stimulated cGMP. Real-time
      PCR showed no effect of dbcAMP on NPR-B transcript at 3 and 6 h, but indicated a
      40% reduction in transcript by dbcAMP at 24 h. In contrast, real-time PCR
      indicated a 5-fold increase in CNP transcript at 3 h, reaching 15.4-fold above
      control at 6 h in cells treated with dbcAMP. In addition, immunofluorescence
      staining of FRTL-5 cells with a specific antibody for CNP-22 showed the presence
      of cytoplasmic CNP that was up-regulated by incubation with either TSH or dbcAMP.
      These results suggested that cAMP signaling regulates the natriuretic peptide
      system in rat thyroid cells by increasing CNP expression, and reducing NPR-B
      activity. This latter action of cAMP appears to be both PKA independent and
      calcium dependent, and provides support for a dominant role for calcium in the
      regulation of NPR-B in the rat thyroid.

PMID- 14709142
TI  - Permissive effects of thyroid hormones on rat anterior pituitary mitotic
      activity.
AB  - The anterior pituitary is active mitotically and apoptotically under basal
      conditions and in response to a variety of physiological and pathophysiological
      stimuli. Hypothyroidism in man is associated with a modest but very occasionally
      dramatic increase in overall pituitary size. The mechanisms underlying this
      reversible phenomenon remain obscure. In the present study we have examined young
      adult rat anterior pituitary following surgical thyroidectomy and subsequent
      thyroid hormone treatment and withdrawal using an extremely accurate system for
      quantifying directly identified mitotic and apoptotic events. Despite the
      expected increase in the number and/or proportion of immunohistochemically
      identifiable thyrotrophs three weeks after thyroidectomy, mitotic and apoptotic
      activity remained unchanged, as did pituitary wet weight, in comparison with sham
      operated and intact controls. In contrast, mitotic but not apoptotic activity was
      enhanced by treatment of thyroidectomized animals with thyroid hormones
      (triiodothyronine (T3) and thyroxine (T4) 1.8 microg and 3.6 microg/100 g body
      weight per day respectively), and once again declined to levels seen in intact
      animals within 72 h of subsequent thyroid hormone withdrawal. Thyroid hormone
      induced enhancement of mitotic activity was also seen in intact rats treated with
      similar doses of thyroid hormones for 7 days and in thyroidectomized rats treated
      for a similar period with very low dose thyroid hormone replacement at a level
      that had no effect on raised hypothalamic TRH- or pituitary TSHbeta-transcript
      prevalence (0.018 microg T3 plus 0.036 microg T4/100 g body weight per day). Thus
      changes in mitotic and apoptotic activity are unlikely to be the principle
      mechanism for the apparent increase in thyrotrophs up to 4 weeks after
      thyroidectomy. In contrast, the data indicate that thyroid hormones have a
      permissive effect on anterior pituitary mitotic activity in thyroidectomized male
      rats. Thyroid hormone-induced enhancement of mitotic activity in intact rats
      further suggests that in euthyroid rats, ambient thyroid hormone levels are a
      limiting factor for anterior pituitary mitotic activity. In summary, this time
      course study of young, male rats has shown for the first time that thyroidectomy,
      thyroid hormone replacement and subsequent withdrawal has no significant effect
      on anterior pituitary apoptotic activity. Secondly, it has shown that the
      anterior pituitary mitotic response to thyroidectomy is blocked by complete
      thyroid hormone deprivation, but can be restored by very low level thyroid
      hormone replacement, and thirdly that in intact animals thyroid hormone levels
      significantly limit anterior pituitary mitotic activity.

PMID- 14709143
TI  - Endogenous thyroid hormones modulate pituitary somatotroph differentiation during
      chicken embryonic development.
AB  - Growth hormone cell differentiation normally occurs between day 14 and day 16 of
      chicken embryonic development. We reported previously that corticosterone (CORT)
      could induce somatotroph differentiation in vitro and in vivo and that thyroid
      hormones could act in combination with CORT to further augment the abundance of
      somatotrophs in vitro. The objective of the present study was to test our
      hypothesis that endogenous thyroid hormones regulate the abundance of
      somatotrophs during chicken embryonic development. Plasma samples were collected
      on embryonic day (e) 9-14. We found that plasma CORT and thyroid hormone levels
      increased progressively in mid-embryogenesis to e 13 or e 14, immediately before
      normal somatotroph differentiation. Administration of thyroxine (T4) and
      triiodothyronine (T3) into the albumen of fertile eggs on e 11 increased
      somatotroph proportions prematurely on e 13 in the developing chick embryos in
      vivo. Furthermore, administration of methimazole, the thyroid hormone synthesis
      inhibitor, on e 9 inhibited somatotroph differentiation in vivo, as assessed on e
      14; this suppression was completely reversed by T3 replacement on e 11. Since we
      reported that T3 alone was ineffective in vitro, we interpret these findings to
      indicate that the effects of treatments in vivo were due to interactions with
      endogenous glucocorticoids. These results indicate that treatment with exogenous
      thyroid hormones can modulate somatotroph abundance and that endogenous thyroid
      hormone synthesis likely contributes to normal somatotroph differentiation.

PMID- 14709144
TI  - Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral
      epithelium and salivary glands.
AB  - Many studies have shown that the oral mucosa and salivary glands are sensitive to
      estrogen action. However, the expression of estrogen receptors (ERs) within these
      tissues is an area of controversy. ERs exist as two subtypes (ERalpha and
      ERbeta), and we hypothesized that the incongruity between ER expression and
      estrogen sensitivity may result from differential expression of ER subtypes in
      oral tissues. To test this hypothesis, we analyzed oral mucosal and salivary
      gland samples for ERalpha and ERbeta protein expression by immunohistochemistry
      from a cross-section of patients attending hospital for surgical problems of the
      head and neck. ERalpha was not detected in oral buccal and gingival epithelium or
      in salivary glands. In contrast, ERbeta was widely expressed at high levels in
      all oral tissues studied. Within these tissues, ERbeta was observed primarily in
      keratinocytes and salivary gland acinar and ductal cells. Our results
      demonstrating the expression of only the ERbeta subtype within oral tissues may
      explain the contradictory results from previous studies investigating ER
      expression in these tissues. Importantly, these results suggest that estrogens
      may act via ERbeta in oral tissues and explain the effect of hormonal changes on
      the oral mucosa as well as on saliva secretion and composition.

PMID- 14709145
TI  - First lactation ovarian function in dairy heifers in relation to prepubertal
      metabolic profiles.
AB  - The aim of this study was to determine whether any differences in the GH-IGF-I
      axis in juvenile calves were predictive of fertility problems as adult cows.
      Endogenous metabolic hormone profiles before and after feeding and the response
      to a GH-releasing factor (GRF) challenge were measured in prepubertal (6 month)
      dairy calves. These metabolic parameters were subsequently related to physical
      characteristics at puberty and to ovarian function during the first lactation.
      Milk progesterone analysis was used to categorize the animals into those with
      normal progesterone profiles following calving (n=17) and those that developed
      delayed ovulation (DOV1, n=9) or persistent corpus luteum (PCL1, n=6) profiles.
      There were associations between prepubertal GH parameters, glucose and non
      esterified fatty acid (NEFA) concentrations and the body condition score at which
      the animals attained puberty. The calves which subsequently developed DOV1
      profiles as cows tended to have a higher GH pulse amplitude during fasting than
      normal profile animals, they did not show the anticipated decrease in circulating
      glucose concentrations following a post-prandial rise in insulin and they also
      had the lowest IGF-I concentrations. The calves that later developed PCL1 had a
      significantly larger GH pulse amplitude and pulse area than normal profile
      animals in the fed period and had the highest IGF-I concentrations. There were no
      differences in prepubertal insulin or NEFA concentrations or in the GH response
      to a GRF challenge between the different progesterone profile categories. Plasma
      IGF-I concentrations in prepubertal animals were positively correlated with their
      post-calving concentrations, whereas glucose concentrations had a negative
      correlation between these time-periods. These results suggested that the
      different juvenile endocrine profiles of the DOV1 cows may predispose them to a
      higher rate of tIssue mobilization during lactation and a consequent reduction in
      fertility, while altered GH and IGF-I levels in PCL1 cows may later contribute to
      the maintenance of the persistent corpus luteum. Therefore metabolic differences
      in prepubertal calves were later reflected by altered reproductive function
      during the first lactation.

PMID- 14709146
TI  - Localization and estrogenic regulation of androgen receptor mRNA expression in
      the mouse uterus and vagina.
AB  - Androgen receptors (AR) are highly expressed in female reproductive organs. In
      order to define the possible involvement of estrogens in the regulation of AR
      expression in the uterus and vagina, we have studied the effect of short-term
      administration of 17beta-estradiol (E2) to ovariectomized adult mice on AR mRNA
      levels. Seven days after ovariectomy, the mice received a single injection of E2
      (0.05 microg/mouse) 3, 12 or 24 h before they were killed. The levels of AR mRNA
      were measured in the different uterine and vaginal compartments using
      quantitative in situ hybridization. In the uterus, AR mRNA was expressed in the
      luminal and glandular epithelial cells, stromal cells and smooth muscle cells. In
      the vagina, AR mRNA was localized in both epithelial and stromal cells. In the
      uterus after ovariectomy, AR mRNA levels were decreased by 18% in the epithelial
      cells, 23% in the stromal cells and 50% in the myometrial cells. AR mRNA levels
      were completely restored as early as 3 h after E2 administration in the
      epithelium and stroma, and at the 12-h time-interval in the myometrium. In the
      vaginal epithelium, ovariectomy induced a 70% decrease in AR mRNA expression. No
      effect could be detected 3 h after E2 administration, while at the longest time
      intervals (12 and 24 h) there was an increase in mRNA levels corresponding to 70%
      of the levels observed in intact animals. In the vaginal stroma, ovariectomy was
      responsible for a 55% decrease in mRNA levels. While no significant changes were
      observed at the 3-h time-interval, a complete restoration of AR mRNA levels in
      stromal cells could be recorded at the longest time-intervals after E2
      administration. The data obtained indicated that, in adult mice, estrogens exert
      a positive regulation of AR mRNA expression in the different compartments of both
      the uterus and the vagina.

PMID- 14709147
TI  - Effect of Lepidium meyenii (Maca) on spermatogenesis in male rats acutely exposed
      to high altitude (4340 m).
AB  - Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between
      4000 and 4500 m in the central Andes. Maca is traditionally employed in the
      Andean region for its supposed fertility-enhancing properties. The aim of this
      study was to test the hypothesis that Maca can prevent high altitude-induced
      testicular disturbances. Adult male rats were exposed for 21 days to an altitude
      of 4340 m and treated with vehicle or aqueous extract of Maca (666.6 mg/day). The
      lengths of the stages of the seminiferous epithelium and epididymal sperm counts
      were obtained at 0, 7, 14 and 21 days of exposure. The stages of the seminiferous
      tubules were assessed by transillumination. A dose-response study was also
      performed at sea level to determine the effect of Maca given to male rats at
      doses of 0, 6.6, 66.6 and 666.6 mg/day for 7 days on body weight, seminiferous
      tubule stages and epididymal sperm count. The length of stage VIII and the
      epididymal sperm count were increased in a dose-dependent manner in Maca-treated
      rats but treatment reduced the length of stage I. At the highest dose, sperm
      count increased 1.58 times, the length of stage VIII increased 2.4 times and the
      length of stage I was reduced 0.48 times compared with the value at dose 0.
      Exposure to high altitude resulted in a reduction in epididymal sperm count after
      7 days and lower values were maintained up to 21 days. Altitude reduced
      spermiation (stage VIII) to half and the onset of spermatogenesis (stages IX-XI)
      to a quarter on days 7 and 14 but treatment with Maca (666.6 mg/day) prevented
      these changes. Data on transillumination and epididymal sperm count in the Maca
      treated group exposed to high altitude were similar to those obtained at sea
      level. Maca increased the sperm count on day 21 of exposure to high altitude to
      values similar (1095.25 +/- 20.41x10(6) sperm, means +/- S.E.M.) to those
      obtained in the Maca-treated group at sea level (1132.30 +/- 172.95x10(6) sperm).
      Furthermore, in the Maca-treated group exposed for 21 days to high altitude,
      epididymal sperm count was higher than in the non-treated group at sea level
      (690.49 +/- 43.67x10(6) sperm). In conclusion, treatment of rats with Maca at
      high altitude prevented high altitude-induced spermatogenic disruption.

PMID- 14709148
TI  - Role of putative membrane receptors in the effect of androgens on human vascular
      cell growth.
AB  - We have reported previously that dihydrotestosterone (DHT) induces a biphasic
      effect on DNA synthesis in human vascular smooth muscle cells (VSMC), i.e.
      stimulation at low concentrations and inhibition at high concentrations. In
      contrast, DHT dose-dependently stimulated [(3)H]thymidine incorporation in a
      human endothelial cell line (ECV304). Additionally, DHT increased the specific
      activity of creatine kinase (CK) in both vascular cell types. In the present
      study, we have determined whether some of these effects are exerted via membrane
      binding sites. We measured changes in DNA synthesis and CK after treatment with
      DHT and the membrane-impermeant testosterone-3-carboxymethyl oxime conjugated to
      bovine serum albumin (BSA) (T-BSA). High concentrations of either DHT or T-BSA
      inhibited VSMC proliferation (by 52+22% and 51+25% respectively). DHT as well as
      T-BSA increased DNA synthesis in ECV304 cells dose-dependently. In contrast, T
      BSA did not affect CK in either cell type. In both cell types, DHT as well as T
      BSA increased mitogen-activated protein kinase (MAPK) kinase activity as measured
      by total phosphorylated MAPK. Further, the inhibitory effect of either the free
      or protein-bound androgens on DNA synthesis was blocked by UO126, an inhibitor of
      MAPK kinase activity. T-BSA conjugate labeled with Europium showed binding to
      whole VSMC, which could be displaced by excess T-BSA, but not by estradiol-BSA or
      the free hormones. Finally, using T-BSA linked to the fluorescent dye Cy3.5, we
      directly demonstrated the presence of membrane-binding sites for androgen in
      VSMC. Hence, the inhibitory effects of testosterone on DNA synthesis in VSMC are
      apparently exerted by membrane-binding sites for androgen, do not require
      intracellular entry of the hormone and its binding to the classical nuclear
      receptors and are linked to MAPK activation.

PMID- 14709149
TI  - Established risk factors for coronary heart disease are unrelated to androgen
      induced baldness in female-to-male transsexuals.
AB  - A high scalp sensitivity to androgens is part of the pathophysiology of male
      pattern baldness (MPB). Androgens affect established risk factors for coronary
      heart disease (CHD), and a supposedly heightened impact on these risk factors is
      hypothesized to explain the epidemiological association between MPB and CHD. In
      this retrospective, observational study we studied 81 female-to-male transsexual
      (F-->M) subjects, mean age 36.7 years (range 21-61), treated with testosterone
      esters (n=61; 250 mg i.m./2 weeks) or testosterone undecanoate (n=20; 160-240
      mg/day orally). The degree of MPB was self-assessed using a 5-point scale (i.e.
      type I (no hair loss) to type V (complete hair loss)). Body mass index, blood
      pressure and levels of lipid and insulin were retrospectively assessed at the
      start of testosterone administration (0.5-24 years before) and between 3 and 4
      months of follow-up. We found that 31 of 81 (38.3%) F-->M transsexuals had MPB
      type II-V. Thinning of hair was related to the duration of androgen
      administration and present in about 50% of F-->M transsexuals after 13 years.
      None of the CHD risk factors at follow-up, nor proportional changes, was
      associated with the degree MPB, except that there was an unexpected tendency of
      lower fasting glucose levels in balding subjects. Therefore, our findings do not
      support the idea that MPB serves as an indicator of increased CHD risk through
      androgenic effects on classic CHD risk factors.

PMID- 14709150
TI  - Adrenocorticotropin induces heme oxygenase-1 expression in adrenal cells.
AB  - Heme oxygenase (HO) catalyzes the first and rate-controlling step of heme
      catabolism into biliverdin, iron and carbon monoxide. Three isoforms of HO have
      been identified so far: the inducible HO-1 and the constitutive HO-2 and HO-3.
      Both HO-1 and HO-2 were expressed in zona fasciculata (ZF) adrenal cells and in a
      mouse adrenocortical cell line (Y1). HO-1 but not HO-2 expression was upregulated
      by adrenocorticotropic hormone (ACTH) and accumulation of HO-1 protein correlated
      with an increase in HO activity in Y1 cells. ACTH induced HO-1 expression in a
      time- and dose-dependent manner with a maximum after 5 h of treatment and a
      threshold concentration of 0.1 mIU/ml. Actinomycin D and cycloheximide completely
      blocked the effect of ACTH on HO-1 mRNA expression whereas mRNA stability was not
      affected by ACTH. Permeable analogs of cAMP mimicked the effect of ACTH on HO-1
      expression and ACTH induction was prevented by the protein kinase A (PKA)
      inhibitor H89. Steroid production was significantly increased when both HO-1 and
      HO-2 activities were inhibited by Sn-protoporphyrin IX (SnPPIX). The lipid
      peroxidation and increase in carbonyl content triggered by hydrogen peroxide was
      prevented by treatment of Y1 cells with bilirubin and ACTH.

PMID- 14709151
TI  - Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the
      human adrenocortical carcinoma cell line H295R.
AB  - A number of conditions related to sex-reversal in boys and men and precocious
      puberty in girls are caused by estrogen-secreting adrenal tumors. In these
      tumors, cytochrome P450 aromatase (aromatase) that is encoded in the CYP19 gene
      is expressed at high levels. To investigate the molecular mechanism of aromatase
      expression in these adrenal tumors, we characterized the activity, gene
      transcript and genomic promoter region of aromatase in the human adrenocortical
      carcinoma cell line H295R. Aromatase activity and the transcript of the CYP19
      gene were highly up-regulated by forskolin, but not by dexamethasone. The results
      from exon I-specific reverse transcriptase (RT)-PCR and the transfection of
      reporter constructs suggested that promoter I.3 and promoter II were activated in
      H295R. Deletion and mutation analysis suggested that cAMP response element-like
      sequence (CLS) and steroidogenic factor-1 (SF-1) motif, were critical for the
      activation of promoter II. The results of this work should provide the basis for
      the molecular analysis of aromatase expression in adrenocortical cells.

PMID- 14709152
TI  - Expression of enzyme associated with steroid hormone synthesis and local
      production of steroid hormone in endometrial carcinoma cells.
AB  - Endometrial carcinoma is a common malignancy of the genital tract. In the present
      study, we examined the expression of human steroidogenic acute regulatory (StAR)
      protein, P450 side-chain cleavage enzyme (P450 scc), 17alpha-hydroxylase/17,20
      desmolase (P45017alpha) and aromatase (P450 arom) in endometrial carcinoma cells
      to clarify the ability of these cells to produce steroid hormones. The results of
      RT-PCR analysis showed that StAR, P450 scc and P45017alpha genes were expressed
      in endometrial carcinoma cells. To examine the protein expression of StAR and
      P450 scc, we performed Western blotting using extracts from carcinoma cells. StAR
      protein and P450 scc were detected in both HHUA and HOUA-1 cells. The production
      of pregnenolone in HHUA cells increased 2.4-fold with transfection of a StAR
      expression vector and 4.3-fold with transfection of an F2 side-chain cleavage
      system. The RT-PCR product of 3beta-hydroxysteroid dehydrogenase was present in
      endometrial carcinoma cells. In endometrial carcinoma cells, the production of
      progesterone also increased with over-expression of StAR and the F2 system.
      Results of steroid metabolic assays showed that endometrial carcinoma cells
      produced not only 17alpha-hydroxyprogesterone but also androstenedione.
      Endometrial carcinoma cells express enzymes that are associated with the
      production of steroid hormones. Locally produced steroid hormones may have
      effects on tumor proliferation and tumorigenesis.

PMID- 14709153
TI  - Impact of chronic catheterization and automated blood sampling (Accusampler) on
      serum corticosterone and fecal immunoreactive corticosterone metabolites and
      immunoglobulin A in male rats.
AB  - Jugular catheters were inserted in nine male rats under general isofluorane
      anesthesia and the catheters were connected to a commercially available
      computerized blood sampling device (Accusampler). Blood samples (150 microl) were
      collected every 4 h during the first 24 h after surgery and every 12 h during the
      following 72 h until 94 h after surgery, when the animals were killed. All fecal
      pellets were collected at blood sampling. Serum corticosterone and fecal
      concentrations of immunoreactive corticosterone metabolites and immunoglobulin A
      (IgA) were quantified by ELISAs. In blood, high corticosterone concentrations
      (>200 ng/ml) were recorded in the first samples obtained after surgery, but the
      concentrations decreased steadily during the day and became cyclical, showing a
      diurnal variation with high levels during evenings and low levels in the
      mornings. The automatic blood sampling itself did not result in recordable
      increases in serum corticosterone concentrations. The time delay between the
      presence of elevated corticosterone levels in blood and in feces was
      approximately 12 h. Fecal immunoreactive corticosterone metabolite levels
      remained elevated during the 94 h study period after surgery. The fecal
      concentrations of IgA showed substantial between-animal variation and decreased
      non-significantly after the surgery. Like serum corticosterone, fecal IgA showed
      a diurnal variation in amounts excreted, in this case with high values in the
      morning and low values in the evening. The concentrations of fecal corticosterone
      and IgA were negatively correlated in samples obtained before surgery but no
      correlation existed after surgery. This indicates that fecal immunoreactive
      corticosterone metabolites, but not IgA, constitute a good marker of acute
      stress. For immunoreactive corticosterone metabolites as well as for IgA, the
      concentration in feces correlated well with total excretion, making single fecal
      samplings usable as a measure of total secretion.

PMID- 14709154
TI  - ACTH stimulates insulin secretion from MIN6 cells and primary mouse and human
      islets of Langerhans.
AB  - It has previously been suggested that ACTH and ACTH-related peptides may act as
      paracrine modulators of insulin secretion in the islets of Langerhans. We have,
      therefore, examined the expression and function of the ACTH receptor (the
      melanocortin 2 receptor, MC2-R) in human and mouse primary islet tIssue and in
      the MIN6 mouse insulinoma cell line. Mouse MC2-R mRNA was detected in both MIN6
      cells and mouse islet tIssue by PCR amplification of cDNA. In perifusion
      experiments with MIN6 pseudo-islets, a small, transient increase in insulin
      secretion was obtained when ACTH(1-24) (1 nM) was added to medium containing 2 mM
      glucose (control) but not when the medium glucose content was increased to 8 mM.
      Further investigations were performed using static incubations of MIN6 cell
      monolayers; ACTH(1-24) (1 pM-10 nM) provoked a concentration-dependent increase
      in insulin secretion from MIN6 monolayer cells that achieved statistical
      significance at concentrations of 1 and 10 nM (150 +/- 13.6% basal secretion; 187
      +/- 14.9% basal secretion, P<0.01). Similar responses were obtained with ACTH(1
      39). The phosphodiesterase inhibitor IBMX (100 microM) potentiated the responses
      to sub-maximal doses of ACTH(1-24). Two inhibitors of the protein kinase A (PKA)
      signaling pathway, Rp-cAMPS (500 microM) and H-89 (10 microM), abolished the
      insulin secretory response to ACTH(1-24) (0.5-10 nM). Treatment with 1 nM ACTH(1
      24) caused a small, statistically significant increase in intracellular cAMP
      levels. Secretory responses of MIN6 cells to ACTH(1-24) were also influenced by
      changes in extracellular Ca2+ levels. Incubation in Ca2+-free buffer supplemented
      with 0.1 mM EGTA blocked the MIN6 cells' secretory response to 1 and 10 nM ACTH(1
      24). Similar results were obtained when a Ca2+ channel blocker (nitrendipine, 10
      microM) was added to the Ca2+-containing buffer. ACTH(1-24) also evoked an
      insulin secretory response from primary tIssues. The addition of ACTH(1-24) (0.5
      nM) to perifusions of mouse islets induced a transient increase in insulin
      secretion at 8 mM glucose. Perifused human primary islets also showed a secretory
      response to ACTH(1-24) at basal glucose concentration (2 mM) with a rapid initial
      spike in insulin secretion followed by a decline to basal levels. Overall the
      results demonstrate that the MC2-R is expressed in beta-cells and suggest that
      activation of the receptor by ACTH initiates insulin secretion through the
      activation of PKA in association with Ca2+ influx into beta-cells.

PMID- 14709155
TI  - Analysis of the effect of leptin on immune function in vivo using diet-induced
      obese mice.
AB  - Leptin can regulate several immune functions. However, the role of leptin on
      lymphocyte function has not been recognized in vivo. Accordingly, we have
      investigated the effect of leptin on starvation-induced immune dysfunction using
      diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat
      diet for 14 weeks and control mice were fed a standard diet for the same period.
      The obese and control groups of mice were then starved for 48 h, and received
      intraperitoneal injections of recombinant leptin or phosphate-buffered saline
      four times during starvation. Other control mice in both diet groups were free
      fed without being starved. Although starvation of the control mice dramatically
      reduced the weights of the immune organs, cytokine production and increased
      proliferation of cultured splenocytes, these levels returned to those of the free
      feeding groups with exogenous leptin administration. However, these effects of
      leptin were not observed in obese mice. These findings provide some evidence that
      leptin can regulate the immune function in vivo. It is also suggested that the
      action of leptin might not appear in obesity.

PMID- 14709156
TI  - Transgenic overexpression of insulin-like growth factor I prevents streptozotocin
      induced cardiac contractile dysfunction and beta-adrenergic response in
      ventricular myocytes.
AB  - Diabetic cardiomyopathy is characterized by cardiac dysfunction and altered
      level/function of insulin-like growth factor I (IGF-I). Both endogenous and
      exogenous IGF-I have been shown to effectively alleviate diabetes-induced cardiac
      dysfunction and oxidative stress. This study was designed to examine the effect
      of cardiac overexpression of IGF-I on streptozotocin (STZ)-induced cardiac
      contractile dysfunction in mouse myocytes. Both IGF-I heterozygous transgenic
      mice and their wild-type FVB littermates were made diabetic with a single
      injection of STZ (200 mg/kg, i.p.) and maintained for 2 weeks. The following
      mechanical indices were evaluated in ventricular myocytes: peak shortening (PS),
      time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of
      shortening/relengthening (+/- dL/dt). Intracellular Ca2+ was evaluated as resting
      and peak intracellular Ca2+ levels, Ca2+-induced Ca2+ release and intracellular
      Ca2+ decay rate (tau). STZ led to hyperglycemia in FVB and IGF-I mice. STZ
      treatment prolonged TPS and TR90, reduced Ca2+-induced Ca2+ release, increased
      resting intracellular Ca2+ levels and slowed tau associated with normal PS and +/
      dL/dt. All of which, except the elevated resting intracellular Ca2+, were
      prevented by the IGF-I transgene. In addition, myocytes from STZ-treated FVB mice
      displayed an attenuated contractile response to the beta-adrenergic agonist
      isoproterenol, which was restored by the IGF-I transgene. Contractile response to
      the alpha-adrenergic agonist phenylephrine and angiotensin II was not affected by
      either STZ treatment or IGF-I. These results validate the beneficial role of IGF
      I in diabetic cardiomyopathy, possibly due to an improved beta-adrenergic
      response.

PMID- 14709157
TI  - Agouti-related protein (83-132) is a competitive antagonist at the human
      melanocortin-4 receptor: no evidence for differential interactions with pro
      opiomelanocortin-derived ligands.
AB  - Interactions between pro-opiomelanocortin (POMC)-derived peptides, agouti-related
      protein (AGRP) and the melanocortin-4 receptor (MC4-R) are central to energy
      homeostasis. In this study we have undertaken comprehensive pharmacological
      analysis of these interactions using a CHOK1 cell line stably transfected with
      human MC4-R. Our main objectives were (1) to compare the relative affinities and
      potencies of POMC-derived peptides endogenously secreted within the hypothalamus,
      (2) to investigate the potency of AGRP(83-132) antagonism with respect to each
      POMC-derived peptide and (3) to determine whether AGRP(83-132) and POMC-derived
      peptides act allosterically or orthosterically. We have found that beta
      melanocyte-stimulating hormone (betaMSH), desacetyl alpha MSH (da-alphaMSH) and
      adrenocorticotrophic hormone all have very similar affinities and potencies at
      the MC4-R compared with the presumed natural ligand, alphaMSH. Moreover, even MSH
      precursors, such as beta lipotrophic hormone, showed significant binding and
      functional activity. Therefore, many POMC-derived peptides could have important
      roles in appetite regulation and it seems unlikely that alphaMSH is the sole
      physiological ligand. We have shown that AGRP(83-132) acts as a competitive
      antagonist. There was no significant difference in the potency of inhibition by
      AGRP(83-132) or agouti(87-132) at the MC4-R, regardless of which POMC peptide was
      used as an agonist. Furthermore, we have found that AGRP(83-132) has no effect on
      the dissociation kinetics of radiolabelled Nle4,D-Phe7 MSH from the MC4-R,
      indicating an absence of allosteric effects. This provides strong pharmacological
      evidence that AGRP(83-132) acts orthosterically at the MC4-R to inhibit Gs
      coupled accumulation of intracellular cAMP.

PMID- 14709158
TI  - Direct stimulation of osteoclastogenesis by MIP-1alpha: evidence obtained from
      studies using RAW264 cell clone highly responsive to RANKL.
AB  - Macrophage inflammatory protein-1alpha (MIP-1alpha) is a member of the CC
      chemokines. We have previously reported the use of a whole bone marrow culture
      system to show that MIP-1alpha stimulates the formation of osteoclast-like
      multinucleated cells. Here we use rat bone marrow cells deprived of stromal
      cells, and clones obtained from murine macrophage-like cell line RAW264 to show
      that MIP-1alpha acts directly on cells in osteoclast lineage. We obtained several
      types of RAW264 cell clones, one of these clones, designated as RAW264 cell D
      clone (D clone), showed an extremely high response to receptor activator of
      NFkappaB ligand (RANKL) and tumor necrosis factor-alpha (TNF-alpha), while the
      other clone, RAW264 cell N clone (N clone), demonstrated no response to RANKL or
      TNF-alpha. Although both clones expressed receptor activator NFkappaB (RANK)
      before being stimulated for differentiation, only the D clone expressed cathepsin
      K when cells were stimulated to differentiate to osteoclasts. MIP-1alpha
      stimulated the formation of mononuclear preosteoclast-like cells from rat bone
      marrow cells deprived of stromal cells. MIP-1alpha also stimulated formation of
      osteoclast-like multinucleated cells from the D clone, when these cells were
      stimulated with RANKL and TNF-alpha. These findings provide strong evidence to
      show that MIP-1alpha acts directly on cells in the osteoclast lineage to
      stimulate osteoclastogenesis. Furthermore, pretreatment of RAW264 cell D clone
      with MIP-1alpha significantly induced adhesion properties of these cells to
      primary osteoblasts, suggesting a crucial role for MIP-1alpha in the regulation
      of the interaction between osteoclast precursors and osteoblasts in
      osteoclastogenesis.

PMID- 14709159
TI  - Changes in pulmonary vascular function after acute methionine loading in normal
      men.
AB  - Elevated blood levels of Hcy (homocysteine) are associated with endothelial
      dysfunction in the systemic and coronary arterial beds. We wished to know if
      similar changes could be detected in the pulmonary circulation, using non
      invasive tests. We studied ten normal young men aged 23-31 years, in whom acute
      hyperhomocysteinaemia was induced by oral ingestion of methionine.
      Cardiopulmonary exercise testing [including measurement of exhaled breath NO
      (nitric oxide)] was performed on two occasions, with and without methionine
      loading. In addition, blood samples for vWf (von Willebrand factor) and factor
      VIIIc were taken as markers of endothelial function. After oral methionine,
      plasma Hcy increased from 11.8 +/- 3.1 to 31.2 +/- 10.3 micromol/l (values are
      means +/- S.D.; P < 0.0001), whereas there was no increase after placebo. After
      exercise there was an increase in V(NO) (NO production) and circulating plasma
      levels of vWf and factor VIIIc, but these were similar in the two tests. Exercise
      time, HR (heart rate) and BP (blood pressure) responses and P V(O2) (peak
      achieved O2 uptake) were also similar in the two tests. V(E) (expiratory minute
      ventilation)/ V(CO2) (CO2 production) was similar in the two groups at rest
      (methionine, 31.9 +/- 3.9; placebo, 30.5 +/- 3.9; P = 0.11), but increased during
      exercise after methionine (at peak, 32.2 +/- 4.6 compared with 29.9 +/- 2.8; P =
      0.016). P(ETCO2) (end-tidal partial pressure of CO2) was also similar in the two
      groups at rest (35.1 +/- 2.9 compared with 36.8 +/- 3.2; P = 0.11), but decreased
      throughout the methionine test (peak 34.1 +/- 4.4 compared with 36.7 +/- 3.5; P =
      0.006). V(E) vs V(CO2) slope also increased in the methionine test (25.2 +/- 2.4
      compared with 22.8 +/- 2.3; P = 0.003). In conclusion, small, but consistent and
      significant, changes in respiratory gas exchange were seen after methionine
      loading, compatible with a V / Q (ventilation/perfusion) mismatch due to
      pulmonary vascular endothelial dysfunction.

PMID- 14709160
TI  - Identification of a Ser/Thr cluster in the C-terminal domain of the human
      prostaglandin receptor EP4 that is essential for agonist-induced beta-arrestin1
      recruitment but differs from the apparent principal phosphorylation site.
AB  - hEP4-R (human prostaglandin E2 receptor, subtype EP4) is a G(s)-linked
      heterotrimeric GPCR (G-protein-coupled receptor). It undergoes agonist-induced
      desensitization and internalization that depend on the presence of its C-terminal
      domain. Desensitization and internalization of GPCRs are often linked to agonist
      induced beta-arrestin complex formation, which is stabilized by phosphorylation.
      Subsequently beta-arrestin uncouples the receptor from its G-protein and links it
      to the endocytotic machinery. The C-terminal domain of hEP4-R contains 38 Ser/Thr
      residues that represent potential phosphorylation sites. The present study aimed
      to analyse the relevance of these Ser/Thr residues for agonist-induced
      phosphorylation, interaction with beta-arrestin and internalization. In response
      to agonist treatment, hEP4-R was phosphorylated. By analysis of proteolytic
      phosphopeptides of the wild-type receptor and mutants in which groups of Ser/Thr
      residues had been replaced by Ala, the principal phosphorylation site was mapped
      to a Ser/Thr-containing region comprising residues 370-382, the presence of which
      was necessary and sufficient to obtain full agonist-induced phosphorylation. A
      cluster of Ser/Thr residues (Ser-389-Ser-390-Thr-391-Ser-392) distal to this
      site, but not the principal phosphorylation site, was essential to allow agonist
      induced recruitment of beta-arrestin1. However, phosphorylation greatly enhanced
      the stability of the beta-arrestin1-receptor complexes. For maximal agonist
      induced internalization, phosphorylation of the principal phosphorylation site
      was not required, but both beta-arrestin1 recruitment and the presence of Ser/Thr
      residues in the distal half of the C-terminal domain were necessary.

PMID- 14709161
TI  - Modelling and bioinformatics studies of the human Kappa-class glutathione
      transferase predict a novel third glutathione transferase family with similarity
      to prokaryotic 2-hydroxychromene-2-carboxylate isomerases.
AB  - The Kappa class of GSTs (glutathione transferases) comprises soluble enzymes
      originally isolated from the mitochondrial matrix of rats. We have characterized
      a Kappa class cDNA from human breast. The cDNA is derived from a single gene
      comprising eight exons and seven introns located on chromosome 7q34-35.
      Recombinant hGSTK1-1 was expressed in Escherichia coli as a homodimer (subunit
      molecular mass approximately 25.5 kDa). Significant glutathione-conjugating
      activity was found only with the model substrate CDNB (1-chloro-2,4
      ditnitrobenzene). Hyperbolic kinetics were obtained for GSH (parameters: K(m)app,
      3.3+/-0.95 mM; V(max)app, 21.4+/-1.8 micromol/min per mg of enzyme), while
      sigmoidal kinetics were obtained for CDNB (parameters: S0.5app, 1.5+/-1.0 mM;
      V(max)app, 40.3+/-0.3 micromol/min per mg of enzyme; Hill coefficient, 1.3),
      reflecting low affinities for both substrates. Sequence analyses, homology
      modelling and secondary structure predictions show that hGSTK1 has (a) most
      similarity to bacterial HCCA (2-hydroxychromene-2-carboxylate) isomerases and (b)
      a predicted C-terminal domain structure that is almost identical to that of
      bacterial disulphide-bond-forming DsbA oxidoreductase (root mean square deviation
      0.5-0.6 A). The structures of hGSTK1 and HCCA isomerase are predicted to possess
      a thioredoxin fold with a polyhelical domain (alpha(x)) embedded between the beta
      strands (betaalphabetaalpha(x)betabetaalpha, where the underlined elements
      represent the N and C motifs of the thioredoxin fold), as occurs in the bacterial
      disulphide-bond-forming oxidoreductases. This is in contrast with the cytosolic
      GSTs, where the helical domain occurs exclusively at the C-terminus
      (betaalphabetaalphabetabetaalphaalpha(x)). Although hGSTK1-1 catalyses some
      typical GST reactions, we propose that it is structurally distinct from other
      classes of cytosolic GSTs. The present study suggests that the Kappa class may
      have arisen in prokaryotes well before the divergence of the cytosolic GSTs.

PMID- 14709162
TI  - Herpes simplex virus VP22-human papillomavirus E2 fusion proteins produced in
      mammalian or bacterial cells enter mammalian cells and induce apoptotic cell
      death.
AB  - Infection by high-risk HPV (human papillomavirus) is supposed to be the primary
      cause of cervical cancer. The HPV E2 protein (E2) is a DNA-binding protein that
      regulates viral gene expression and is required for efficient viral replication.
      Overexpression of the E2 protein in cervical cancer cells can induce growth
      arrest and/or apoptotic cell death, suggesting that E2 might be useful in the
      treatment of this disease. In the present study, we show that VP22 (herpes
      simplex virus VP22 protein) can be used to deliver E2 to target cells. VP22-E2
      fusion proteins induce apoptosis in transiently transfected HPV-transformed
      cervical carcinoma cell lines. However, VP22-E2 fusion proteins do not kill COS-7
      cells, probably because these cells constitutively express the simian-virus-40 T
      antigen and this protein sequesters the tumour suppressor protein p53. When COS-7
      cells producing VP22-E2 are seeded into cultures of HPV-transformed cells, VP22
      E2 enters the non-producing cells and induces apoptosis. VP22-E2 proteins
      produced in bacterial cells can also enter cervical cancer cells and induce
      apoptosis in a dose-dependent manner. Our results suggest that local delivery of
      VP22-E2 fusion proteins could be used to treat cervical cancer and other HPV
      associated diseases.

PMID- 14709163
TI  - Pulmonary surfactant protein A isolation as a by-product of porcine pulmonary
      surfactant production.
AB  - A pulmonary surfactant reduces surface tension at the air/liquid interface of the
      alveoli and stabilizes alveoli at low lung volumes. Surfactant deficiency and
      dysfunction were shown to be present in a number of pulmonary diseases, and
      surfactant replacement therapy is the common clinical conduct. The hydrophilic SP
      A (surfactant protein A) is absent when solvent extraction was used during
      exogenous surfactant production. Addition of SP-A to the surfactant preparation
      increases the surface activity and completely counteracts inhibition by blood
      proteins. SP-A recognizes and binds to carbohydrate structures on the surfaces of
      pathogenic micro-organisms, and acts as opsonins or cross-linking molecules by
      binding to a variety of cells that participate in the pulmonary immune response.
      The purification procedure yielded 206 mg of high-purity SP-A/kg of porcine lung,
      as judged by gel filtration, SDS/PAGE and Western blotting. The electrophoretic
      profiles obtained showed that pure SP-A consists of proteins of wide molecular
      mass in the range 26-36 kDa and a dimer in the range 56-60 kDa. The Western-blot
      results displayed the same band pattern profile after incubating the membrane
      using a commercially available polyclonal anti-SP-A antibody produced in goat.
      Gel-filtration experiments confirmed the molecular mass of SP-A in 10 mM NaCl
      solution. The isolated SP-A showed mannose-binding ability, representative of its
      functionality.

PMID- 14709164
TI  - Live and let diet.
AB  - It used to be that one's generation could be defined simply by the war one fought
      in. Since the middle of the last century, equally defining are the diets that
      each generation has been swept up in.

PMID- 14709166
TI  - Scratching the (T cell) surface.
AB  - Using a genome-scale approach to study transcription levels in a human CD8+ T
      cell clone, a recent study has suggested that the repertoire of molecules on the
      surface of T cells is close to being completely characterized.

PMID- 14709167
TI  - Characterization of the Schistosoma transcriptome opens up the world of helminth
      genomics.
AB  - Among the metazoan parasites that cause debilitating disease in man, schistosomes
      are the first group for which near-complete transcriptome complements have been
      described. This new genomic information will have an enormous impact on all
      future investigations into the biology, pathogenesis and control of
      schistosomiasis.

PMID- 14709165
TI  - Computational prediction of transcription-factor binding site locations.
AB  - Identifying genomic locations of transcription-factor binding sites, particularly
      in higher eukaryotic genomes, has been an enormous challenge. Various
      experimental and computational approaches have been used to detect these sites;
      methods involving computational comparisons of related genomes have been
      particularly successful.

PMID- 14709168
TI  - How many genes in a genome?
AB  - Despite the current good level of annotation, the Drosophila genome still holds
      surprises. A recent study has added perhaps 2,000 genes to the predicted total,
      and raises a number of questions about how genome annotation data should be
      stored and presented.

PMID- 14709169
TI  - Unveiling the gene-expression profile of pollen.
AB  - Four recent papers have characterized the transcription profile of pollen grains,
      showing striking differences between gene expression in pollen and other plant
      tissues. These studies increase the number of known pollen-expressed genes by as
      much as 50-fold and have identified many novel genes that are potentially pollen
      specific.

PMID- 14709170
TI  - The not-so-humble worm.

PMID- 14709171
TI  - Frontiers in plant genetics.

PMID- 14709172
TI  - Spiralians in the limelight.

PMID- 14709173
TI  - MicroRNA targets in Drosophila.
AB  - BACKGROUND: The recent discoveries of microRNA (miRNA) genes and characterization
      of the first few target genes regulated by miRNAs in Caenorhabditis elegans and
      Drosophila melanogaster have set the stage for elucidation of a novel network of
      regulatory control. We present a computational method for whole-genome prediction
      of miRNA target genes. The method is validated using known examples. For each
      miRNA, target genes are selected on the basis of three properties: sequence
      complementarity using a position-weighted local alignment algorithm, free
      energies of RNA-RNA duplexes, and conservation of target sites in related
      genomes. Application to the D. melanogaster, Drosophila pseudoobscura and
      Anopheles gambiae genomes identifies several hundred target genes potentially
      regulated by one or more known miRNAs. RESULTS: These potential targets are rich
      in genes that are expressed at specific developmental stages and that are
      involved in cell fate specification, morphogenesis and the coordination of
      developmental processes, as well as genes that are active in the mature nervous
      system. High-ranking target genes are enriched in transcription factors two-fold
      and include genes already known to be under translational regulation. Our results
      reaffirm the thesis that miRNAs have an important role in establishing the
      complex spatial and temporal patterns of gene activity necessary for the orderly
      progression of development and suggest additional roles in the function of the
      mature organism. In addition the results point the way to directed experiments to
      determine miRNA functions. CONCLUSIONS: The emerging combinatorics of miRNA
      target sites in the 3' untranslated regions of messenger RNAs are reminiscent of
      transcriptional regulation in promoter regions of DNA, with both one-to-many and
      many-to-one relationships between regulator and target. Typically, more than one
      miRNA regulates one message, indicative of cooperative translational control.
      Conversely, one miRNA may have several target genes, reflecting target
      multiplicity. As a guide to focused experiments, we provide detailed online
      information about likely target genes and binding sites in their untranslated
      regions, organized by miRNA or by gene and ranked by likelihood of match. The
      target prediction algorithm is freely available and can be applied to whole
      genome sequences using identified miRNA sequences.

PMID- 14709174
TI  - Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae.
AB  - BACKGROUND: Although the protein-coding sequences in the Saccharomyces cerevisiae
      genome have been studied and annotated extensively, much less is known about the
      extent and characteristics of the untranslated regions of yeast mRNAs. RESULTS:
      We developed a 'Virtual Northern' method, using DNA microarrays for genome-wide
      systematic analysis of mRNA lengths. We used this method to measure mRNAs
      corresponding to 84% of the annotated open reading frames (ORFs) in the S.
      cerevisiae genome, with high precision and accuracy (measurement errors +/- 6
      7%). We found a close linear relationship between mRNA lengths and the lengths of
      known or predicted translated sequences; mRNAs were typically around 300
      nucleotides longer than the translated sequences. Analysis of genes deviating
      from that relationship identified ORFs with annotation errors, ORFs that appear
      not to be bona fide genes, and potentially novel genes. Interestingly, we found
      that systematic differences in the total length of the untranslated sequences in
      mRNAs were related to the functions of the encoded proteins. CONCLUSIONS: The
      Virtual Northern method provides a practical and efficient method for genome
      scale analysis of transcript lengths. Approximately 12-15% of the yeast genome is
      represented in untranslated sequences of mRNAs. A systematic relationship between
      the lengths of the untranslated regions in yeast mRNAs and the functions of the
      proteins they encode may point to an important regulatory role for these
      sequences.

PMID- 14709176
TI  - Identification of androgen-coregulated protein networks from the microsomes of
      human prostate cancer cells.
AB  - BACKGROUND: Androgens play a critical role in the development of prostate cancer
      dysregulation of androgen-regulated growth pathways can led to hormone-refractory
      prostate cancer. A comprehensive understanding of androgen-regulated cellular
      processes has not been achieved to date. To this end, we have applied a large
      scale proteomic approach to define cellular processes that are responsive to
      androgen treatment in LNCaP prostate cancer cells. RESULTS: Using isotope-coded
      affinity tags and mass spectrometry we identified and quantified the relative
      abundance levels of 1,064 proteins and found that distinct cellular processes
      were coregulated by androgen while others were essentially unaffected. Subsequent
      pharmacological perturbation of the cellular process for energy generation
      confirmed that androgen starvation had a profound effect on this pathway.
      CONCLUSIONS: Our results provide evidence for the role of androgenic hormones in
      coordinating the expression of critical components involved in distinct cellular
      processes and further establish a foundation for the comprehensive reconstruction
      of androgen-regulated protein networks and pathways in prostate cancer cells.

PMID- 14709177
TI  - Antisense transcripts with rice full-length cDNAs.
AB  - BACKGROUND: Natural antisense transcripts control gene expression through post
      transcriptional gene silencing by annealing to the complementary sequence of the
      sense transcript. Because many genome and mRNA sequences have become available
      recently, genome-wide searches for sense-antisense transcripts have been
      reported, but few plant sense-antisense transcript pairs have been studied. The
      Rice Full-Length cDNA Sequencing Project has enabled computational searching of a
      large number of plant sense-antisense transcript pairs. RESULTS: We identified
      sense-antisense transcript pairs from 32,127 full-length rice cDNA sequences
      produced by this project and public rice mRNA sequences by aligning the cDNA
      sequences with rice genome sequences. We discovered 687 bidirectional transcript
      pairs in rice, including sense-antisense transcript pairs. Both sense and
      antisense strands of 342 pairs (50%) showed homology to at least one expressed
      sequence tag other than that of the pair. Microarray analysis showed 82 pairs
      (32%) out of 258 pairs on the microarray were more highly expressed than the
      median expression intensity of 21,938 rice transcriptional units. Both sense and
      antisense strands of 594 pairs (86%) had coding potential. CONCLUSIONS: The large
      number of plant sense-antisense transcript pairs suggests that gene regulation by
      antisense transcripts occurs in plants and not only in animals. On the basis of
      our results, experiments should be carried out to analyze the function of plant
      antisense transcripts.

PMID- 14709178
TI  - Functional classification of proteins for the prediction of cellular function
      from a protein-protein interaction network.
AB  - We here describe PRODISTIN, a new computational method allowing the functional
      clustering of proteins on the basis of protein-protein interaction data. This
      method, assessed biologically and statistically, enabled us to classify 11% of
      the Saccharomyces cerevisiae proteome into several groups, the majority of which
      contained proteins involved in the same biological process(es), and to predict a
      cellular function for many otherwise uncharacterized proteins.

PMID- 14709179
TI  - Recombining overlapping BACs into a single larger BAC.
AB  - BACKGROUND: BAC clones containing entire mammalian genes including all the
      transcribed region and long range controlling elements are very useful for
      functional analysis. Sequenced BACs are available for most of the human and mouse
      genomes and in many cases these contain intact genes. However, large genes often
      span more than one BAC, and single BACs covering the entire region of interest
      are not available. Here we describe a system for linking two or more overlapping
      BACs into a single clone by homologous recombination. RESULTS: The method was
      used to link a 61-kb insert carrying the final 5 exons of the human CFTR gene
      onto a 160-kb BAC carrying the first 22 exons. Two rounds of homologous
      recombination were carried out in the EL350 strain of bacteria which can be
      induced for the Red genes. In the first round, the inserts of the two overlapping
      BACs were subcloned into modified BAC vectors using homologous recombination. In
      the second round, the BAC to be added was linearised with the very rare-cutting
      enzyme I-PpoI and electroporated into recombination efficient EL350 bacteria
      carrying the other BAC. Recombined BACs were identified by antibiotic selection
      and PCR screening and 10% of clones contained the correctly recombined 220-kb
      BAC. CONCLUSION: The system can be used to link the inserts from any overlapping
      BAC or PAC clones. The original orientation of the inserts is not important and
      desired regions of the inserts can be selected. The size limit for the fragments
      recombined may be larger than the 61 kb used here and multiple BACs in a contig
      could be combined by alternating use of the two pBACLink vectors. This system
      should be of use to many investigators wishing to carry out functional analysis
      on large mammalian genes which are not available in single BAC clones.

PMID- 14709180
TI  - A comparative analysis of data generated using two different target preparation
      methods for hybridization to high-density oligonucleotide microarrays.
AB  - BACKGROUND: To generate specific transcript profiles, one must isolate homogenous
      cell populations using techniques that often yield small amounts of RNA,
      requiring researchers to employ RNA amplification methods. The data generated by
      using these methods must be extensively evaluated to determine any technique
      dependent distortion of the expression profiles. RESULTS: High-density
      oligonucleotide microarrays were used to perform experiments for comparing data
      generated by using two protocols, an in vitro transcription (IVT) protocol that
      requires 5 microg of total RNA and a double in vitro transcription (dIVT)
      protocol that requires 200 ng of total RNA for target preparation from RNA
      samples extracted from a normal and a cancer cell line. In both cell lines, about
      10% more genes were detected with IVT than with dIVT. Genes were filtered to
      exclude those that were undetected on all arrays. Hierarchical clustering using
      the 9,482 genes that passed the filter showed that the variation attributable to
      biological differences between samples was greater than that introduced by
      differences in the protocols. We analyzed the behavior of these genes separately
      for each protocol by using a statistical model to estimate the posterior
      probability of various levels of fold change. At each level, more differentially
      expressed genes were detected with IVT than with dIVT. When we checked for genes
      that had a posterior probability greater than 99% of fold change greater than 2,
      in data generated by IVT but not dIVT, more than 60% of these genes had posterior
      probabilities greater than 90% in data generated by dIVT. Both protocols
      identified the same functional gene categories to be differentially expressed.
      Differential expression of selected genes was confirmed using quantitative real
      time PCR. CONCLUSION: Using nanogram quantities on total RNA, the usage of dIVT
      protocol identified differentially expressed genes and functional categories
      consistent with those detected by the IVT protocol. There was a loss in
      sensitivity of about 10% when detecting differentially expressed genes using the
      dIVT protocol. However, the lower amount of RNA required for this protocol, as
      compared to the IVT protocol, renders this methodology a highly desirable one for
      biological systems where sample amounts are limiting.

PMID- 14709175
TI  - An integrated gene annotation and transcriptional profiling approach towards the
      full gene content of the Drosophila genome.
AB  - BACKGROUND: While the genome sequences for a variety of organisms are now
      available, the precise number of the genes encoded is still a matter of debate.
      For the human genome several stringent annotation approaches have resulted in the
      same number of potential genes, but a careful comparison revealed only limited
      overlap. This indicates that only the combination of different computational
      prediction methods and experimental evaluation of such in silico data will
      provide more complete genome annotations. In order to get a more complete gene
      content of the Drosophila melanogaster genome, we based our new D. melanogaster
      whole-transcriptome microarray, the Heidelberg FlyArray, on the combination of
      the Berkeley Drosophila Genome Project (BDGP) annotation and a novel ab initio
      gene prediction of lower stringency using the Fgenesh software. RESULTS: Here we
      provide evidence for the transcription of approximately 2,600 additional genes
      predicted by Fgenesh. Validation of the developmental profiling data by RT-PCR
      and in situ hybridization indicates a lower limit of 2,000 novel annotations,
      thus substantially raising the number of genes that make a fly. CONCLUSIONS: The
      successful design and application of this novel Drosophila microarray on the
      basis of our integrated in silico/wet biology approach confirms our expectation
      that in silico approaches alone will always tend to be incomplete. The
      identification of at least 2,000 novel genes highlights the importance of
      gathering experimental evidence to discover all genes within a genome. Moreover,
      as such an approach is independent of homology criteria, it will allow the
      discovery of novel genes unrelated to known protein families or those that have
      not been strictly conserved between species.

PMID- 14709182
TI  - Report from the CDC. Telephone focus groups: an emerging method in public health
      research.
AB  - BACKGROUND: The focus group is a widely used qualitative method in public health
      research. Typically, focus groups involve face-to-face interaction, although
      focus groups have also been conducted via telephone conference calls. METHODS:
      The indexed medical and social sciences literature was reviewed to assess what is
      empirically known about the telephone focus group method and how this method has
      been used to explore health topics. RESULTS: Thirteen studies reported in 16
      publications were found that used telephone focus groups. Of the 13 studies, 12
      investigated health topics, and none explored any methodological issues. Some
      health studies used the telephone focus group method exclusively, whereas others
      used it in conjunction with additional methods. The studies involved a variety of
      lay and professional populations in six countries and explored a range of topics.
      Several of the studies included participants from a wide geographic area, such as
      across the entire United States. Two rationales for using the telephone focus
      group method were reported: assembling geographically disparate participants and
      increasing participant anonymity by eliminating visual contact. CONCLUSIONS:
      Health researchers appear to be the primary users of the telephone focus group
      method for academic research. The telephone focus group method may be especially
      useful in health studies involving populations that do not have adequate
      representation in any single region and studies investigating sensitive topics.
      Methods studies are needed to compare the group dynamics of telephone and in
      person focus groups and determine the most appropriate size and duration for
      telephone focus groups.

PMID- 14709183
TI  - Toward optimal health: the experts discuss management of low back pain in women.
      Interview by Jodi Godfrey Meisler.

PMID- 14709184
TI  - Sexual trauma and pregnancy: a conceptual framework.
AB  - In this paper, we propose that a history of sexual traumatization is associated
      with pregnancy complications and poor pregnancy-related outcomes. We further
      hypothesize that this relationship is mediated by the sequelae of trauma
      (psychopathology, health problems, and increased negative health behaviors). We
      review the literature linking sexual trauma with psychopathology, health, and
      health behavior and then outline the impact of these variables on pregnancy.
      Based on this review, we draw conclusions about the potential impact of sexual
      trauma on pregnancy outcomes. We suggest future directions for this area of
      research and discuss the clinical implications of this association, including the
      development of prenatal intervention and prevention programs.

PMID- 14709185
TI  - The importance of estrogen replacement in young women with Turner syndrome.
AB  - BACKGROUND: Most girls with Turner syndrome (TS) need estrogen replacement
      treatment (ERT) to induce and maintain feminization and prevent osteoporosis.
      There is abundant information on ERT use in postmenopausal women, but there is
      little information on this issue in women with TS. We aimed to determine the
      level of ERT use in women with TS living in the United States and assess the
      effects of ERT adherence vs. nonadherence on bone mineral density (BMD). METHODS:
      Fifty women with TS aged 30-59 years had ERT history obtained by structured
      interviews and BMD assessed at the lumbar spine by dual x-ray absorptiometry
      (DXA) and quantitative computed tomography (QCT). RESULTS: Thirty-four of the 50
      women with TS had received ERT according to current recommendations, and the rest
      did not either because of physician failure to prescribe (5 of 50) or because of
      nonadherence to prescribed ERT (11 of 50). The mean duration of ERT was 25 +/- 2
      years for the standard of care group vs. 8 +/- 2 years for the others (p <
      0.0001). The major factor promoting adherence to ERT was education on the
      importance of ERT for bone health (p < 0.001). As expected, lumbar spine BMD was
      significantly reduced in women not taking ERT according to current guidelines
      (e.g., a reduction of 20% by QCT, p < 0.001) with 6 of 16 of these women having
      osteoporosis and 3 of 16 having vertebral compression fractures compared with 0
      of 34 in the ERT adherent group. CONCLUSIONS: Approximately 70% of women with TS
      in this sample of highly educated women in the United States are taking ERT as
      currently recommended and appear to be protected from osteoporosis of the spine,
      whereas those women using ERT less than 75% of the time are at grave risk for
      osteoporosis. In a time of new reservations about postmenopausal ERT, it is
      important to emphasize to young women with TS and their caregivers that ERT is
      critical for bone health.

PMID- 14709186
TI  - Candida transmission and sexual behaviors as risks for a repeat episode of
      Candida vulvovaginitis.
AB  - OBJECTIVE: To assess associations between female and male factors and the risk of
      recurring Candida vulvovaginitis. METHODS: A prospective cohort study of 148
      women with Candida vulvovaginitis and 78 of their male sexual partners was
      conducted at two primary care practices in the Ann Arbor, Michigan, area.
      RESULTS: Thirty-three of 148 women developed at least one further episode of
      Candida albicans vulvovaginitis within 1 year of follow-up. Cultures of Candida
      species from various sites of the woman (tongue, feces, vulva, and vagina) and
      from her partner (tongue, feces, urine, and semen) did not predict recurrences.
      Female factors associated with recurrence included recent masturbating with
      saliva (hazard ratio 2.66 [95% CI 1.17-6.06]) or cunnilingus (hazard ratio 2.94
      [95% CI 1.12-7.68]) and ingestion of two or more servings of bread per day (p </=
      0.05). Male factors associated with recurrences in the woman included history of
      the male masturbating with saliva in the previous month (hazard ratio 3.68 [95%
      CI 1.24-10.87]) and lower age at first intercourse (hazard ratio 0.83 [95% CI
      0.71-0.96]). CONCLUSIONS: Sexual behaviors, rather than the presence of Candida
      species at various body locations of the male partner, are associated with
      recurrences of C. albicans vulvovaginitis.

PMID- 14709187
TI  - Structured diet and physical activity prevent postpartum weight retention.
AB  - BACKGROUND: Postpregnancy weight retention contributes to the near-epidemic
      prevalence of obesity in the United States. This study examines the impact of an
      individualized, structured diet and physical activity intervention on weight loss
      in overweight women during the first year postpartum. METHODS: Forty overweight
      postpartum women were randomized to either a structured (STR) or a self-directed
      (SELF) intervention. Measurements included body weight, percent body fat, daily
      caloric intake, habitual physical activity, and cardiorespiratory fitness.
      Subjects in STR received individualized diet and physical activity prescriptions
      derived from baseline measurements. They met weekly for the first 12 weeks and
      kept daily food and activity diaries. Subjects in SELF received a single 1-hour
      educational session about diet and activity. RESULTS: Only 23 of 40 participants
      remained in the study at 1 year postpartum. Of those, STR (n = 13) had a
      significant weight loss (7.3 kg, p < 0.01), a significant decrease in percent
      body fat (6%, p < 0.01), and no change in fat-free mass. SELF (n = 10) had no
      significant change in weight, percent body fat, or fat-free mass. CONCLUSIONS:
      Women who committed to this one class per week for 12 weeks postpartum had a high
      likelihood of successful weight loss that persisted at 1 year. Women who were
      overweight before pregnancy were unlikely to lose the pregnancy-related weight
      without the help of a formal intervention. This suggests that healthcare
      professionals should strongly encourage postpartum women to enroll in a
      structured diet and exercise program.

PMID- 14709188
TI  - Women in academic medicine: a report of focus groups and questionnaires, with
      conjoint analysis.
AB  - BACKGROUND: The percentage of women graduating from U.S. medical schools has
      increased dramatically over the past 30 years, but the distribution of women and
      men across faculty ranks in academic medical centers has remained nearly
      unchanged. Women remain underrepresented in the senior ranks of academic
      medicine. The purpose of the study was to evaluate the work environment at Duke
      University Medical Center, with particular emphasis on gender climate. METHODS:
      An independent firm conducted structured focus groups and administered
      questionnaires, analyzed through conjoint analysis. Focus groups were stratified
      by rank and included the following groups of women: medical students, residents,
      fellows, junior faculty, senior faculty, and women in fields with few women.
      RESULTS: The conjoint analysis demonstrated that the women placed high value on
      the quality of their personal and work lives and rated these as more important
      than other traditional markers of career success, such as stature of their
      institution or earnings potential. Discussions during the focus groups elaborated
      on what "quality of personal and professional life" meant. They described a need
      for career efficiencies that allow individuals to excel professionally while also
      honoring their personal values and responsibilities. The discussions also
      suggested that similar problems have increasing importance for men. CONCLUSIONS:
      The results suggest that institutions should provide more alternative models of
      success and increase flexible work options. Future studies of women in academic
      medicine should explore the role of value conflict in career development in
      academic medicine and probe the idea that the priorities articulated by the women
      in these focus groups may reflect the values of a generation as much as they do
      gender.

PMID- 14709189
TI  - A "ton of feathers": gender discrimination in academic medical careers and how to
      manage it.
AB  - PURPOSE: To evaluate the experience of gender discrimination among a limited
      sample of women in academic medicine, specifically, the role of discrimination in
      hindering careers, coping mechanisms, and perceptions of what institutions and
      leaders of academic medicine can do to improve the professional workplace climate
      for women. METHODS: In-depth, semistructured telephonic individual interviews of
      18 women faculty who experienced or may have experienced discrimination in the
      course of their professional academic medical careers from 13 of the 24
      institutions of the National Faculty Survey. A consensus taxonomy for classifying
      content evolved from comparisons of coding. Themes expressed by multiple faculty
      were studied for patterns of connection and grouped into broader categories.
      RESULTS: Forty percent of respondents ranked gender discrimination first out of
      11 possible choices for hindering their career in academic medicine. Thirty-five
      percent ranked gender discrimination second to either "limited time for
      professional work" or "lack of mentoring." Respondents rated themselves as poorly
      prepared to deal with gender discrimination and noted effects on professional
      self-confidence, self-esteem, collegiality, isolation, and career satisfaction.
      The hierarchical structure in academe is perceived to work against women, as
      there are few women at the top. Women faculty who have experienced gender
      discrimination perceive that little can be done to directly address this issue.
      Institutions need to be proactive and recurrently evaluate the gender climate, as
      well as provide transparent information and fair scrutiny of promotion and salary
      decisions. CONCLUSIONS: According to this subset of women who perceive that they
      have been discriminated against based on gender, sexual bias and discrimination
      are subtly pervasive and powerful. Such environments may have consequences for
      both women faculty and academic medicine, affecting morale and dissuading younger
      trainees from entering academic careers. Medical schools need to evaluate and may
      need to improve the environment for women in academe.

PMID- 14709190
TI  - Pregnancy with chronic kidney disease: outcome in Indian women.
AB  - BACKGROUND: Fetal survival and the risk of accelerated renal damage are the two
      major concerns with pregnancies complicated by chronic kidney disease. Although
      fetal survival has increased significantly due to improved antenatal and neonatal
      services, the maternal and neonatal morbidity is still considerable. METHODS:
      This retrospective analysis of 51 pregnancies was conducted at a tertiary care
      center in India to estimate the risk of obstetrical complications, perinatal
      morbidity and mortality, and the effect of pregnancy on renal function in women
      with different types and severity of renal disease. RESULTS: The type of renal
      disease and the degree of renal insufficiency did not have a significant effect
      on the chances of successful pregnancy outcome once the pregnancy had progressed
      beyond the first trimester. The risk of prematurity was significantly increased
      when the diastolic blood pressure was >/= 90 mm Hg at conception (OR 8.3, CI 1.6
      41.5). All patients with a diastolic blood pressure > 100 mm Hg delivered
      preterm. Hypertension worsened in 16 (35.5%) women during pregnancy, of which 13
      had to be terminated preterm because of uncontrolled blood pressure. Serum
      creatinine deteriorated during pregnancy in 32.5%, the percentage increase
      showing a significant inverse correlation to the baseline creatinine clearance.
      CONCLUSIONS: Hypertension at conception was a significant independent factor
      influencing the gestational age at delivery. The baseline renal function did not
      correlate with the risk of acceleration of hypertension during pregnancy.
      However, the deterioration of renal function during pregnancy had a significant
      inverse correlation to basal creatinine clearance.

PMID- 14709191
TI  - Postmenopausal hormone therapy and migraine headache.
AB  - BACKGROUND: Estrogen withdrawal has been described as a trigger for migraine
      headache, and some studies suggest that estrogen and progestin may exacerbate
      migraine. No population-based studies have examined the association between
      hormone therapy (HT) and migraine among postmenopausal women. METHODS: To examine
      the association between HT and migraine headache in postmenopausal women, we used
      self-report of HT use, HT characteristics, and migraine headache within the past
      year among 17,107 postmenopausal female health professionals enrolled in the
      Women's Health Study. RESULTS: Analyses were restricted to the 17,107 of 21,788
      postmenopausal women who were postmenopausal at baseline and who were never
      (38.5%) or current (61.5%) users of HT. Of these, 1,909 (11.2%) experienced
      migraine headache within the last year. Women with migraine headache were
      significantly younger, had a younger age at menopause, were more likely to have
      had a surgical menopause, and were more likely to be current users of HT. After
      adjusting for age, race, smoking, alcohol use, ever use of oral contraception,
      age at menopause, and menopause type, the odds ratio (OR) for migraine headache
      was 1.42 (95% CI 1.24-1.62) for women who were current users of HT compared with
      never users. ORs were similar for users of estrogen alone (OR 1.39, 95% CI 1.14
      1.69) and users of both estrogen and progestin (OR 1.41, 95% CI 1.22-1.63).
      CONCLUSIONS: In this cross-sectional study, current HT use was associated with
      higher rates of migraine headache than nonuse. Clinical trials are needed to
      determine if HT increases the incidence of migraine in postmenopausal women.

PMID- 14709192
TI  - Nonadherence and osteoporosis treatment preferences of older women: a qualitative
      study.
AB  - BACKGROUND: Physicians must have an understanding of patients' medication beliefs
      in order to enhance medication adherence. To increase understanding, this study
      examined how beliefs about medication and four osteoporosis treatments influenced
      treatment selection and adherence. METHODS: Six focus groups, three with 28
      African Americans and one with 11 non-Hispanic white women, were conducted in
      English. Two groups with 16 Hispanics were conducted in Spanish. The convenience
      sample was recruited from senior centers and housing in lower socioeconomic
      geographic areas. The average age was 74.8 +/- 1.1 years. RESULTS: Adherence was
      associated with recognition of the serious consequences of nonadherence,
      realization of the beneficial effects, and the belief that medicines are not
      harmful. Doubts about physicians' competence to prescribe appropriate drugs were
      also revealed. Women who thought they were unlikely to fracture or perceived
      fracture outcomes as not severe chose no treatment. If they identified a need,
      they weighed benefits against the attendant risks to find the best alternative
      among the affordable options. Price considerations eliminated raloxifene and
      alendronate. Consideration of side effects eliminated estrogen and raloxifene.
      Calcium was viewed as a low-cost, low-risk alternative. Those who could afford
      alendronate and who viewed its side effects as preventable preferred it. Benefit
      and risk assessments may have been biased by fear of cancer and thromboembolic
      events. CONCLUSIONS: Women's beliefs about necessity of treatment, medication
      safety, cost of treatment, and treatment goals appear critical to osteoporosis
      treatment selection and adherence.

PMID- 14709194
TI  - Technology for portable measurement of blood lactate.

PMID- 14709195
TI  - A multicenter study of the accuracy of the One Touch Ultra home glucose meter in
      children with type 1 diabetes.
AB  - Data are not readily available on the accuracy of one of the most commonly used
      home blood glucose meters, the One Touch Ultra (LifeScan, Milpitas, California).
      The purpose of this report is to provide information on the accuracy of this home
      glucose meter in children with type 1 diabetes. During a 24-h clinical research
      center stay, the accuracy of the Ultra meter was assessed in 91 children, 3-17
      years old, with type 1 diabetes by comparing the Ultra glucose values with
      concurrent reference serum glucose values measured in a central laboratory. The
      Pearson correlation between the 2,068 paired Ultra and reference values was 0.97,
      with the median relative absolute difference being 6%. Ninety-four percent of all
      Ultra values (96% of venous and 84% of capillary samples) met the proposed
      International Organisation for Standardisation (ISO) standard for instruments
      used for self-monitoring of glucose when compared with venous reference values.
      Ninety-nine percent of values were in zones A + B of the Modified Error Grid. A
      high degree of accuracy was seen across the full range of glucose values. For 353
      data points during an insulin-induced hypoglycemia test, the Ultra meter was
      found to have accuracy that was comparable to concurrently used benchmark
      instruments (Beckman, YSI, or i-STAT); 95% and 96% of readings from the Ultra
      meter and the benchmark instruments met the proposed ISO criteria, respectively.
      These results confirm that the One Touch Ultra meter provides accurate glucose
      measurements for both hypoglycemia and hyperglycemia in children with type 1
      diabetes.

PMID- 14709196
TI  - A fully implantable subcutaneous glucose sensor array: enhanced accuracy from
      multiple sensing units and a median-based algorithm.
AB  - Although continuous electrochemical glucose monitoring holds promise in the
      management of diabetes, its utility is limited in part because of error of
      unclear origin. The use of redundant glucose sensors in an array might reduce
      such error. We hypothesized that in a subcutaneously implanted array, a median
      based continuous computation that excludes outlying data would lead to more
      accurate glucose measurement than averaging of all signals. Each rat was
      implanted with an array of four sensing units, and each unit transmitted data
      independently to an external monitoring device. Animals underwent perturbation of
      glucose by insulin infusions in diabetic animals and glucose infusions in
      nondiabetic animals, and in both, capillary glucose monitoring was performed
      frequently. Repeat glucose perturbation studies were performed every 1-2 weeks.
      We observed that a median-based technique, the Z-score with Median Absolute
      Deviation (ZMAD), consistently led to greater sensing accuracy as compared with
      signal averaging. The ZMAD technique yielded a correlation coefficient of 0.93,
      and 96% of values fell in the A and B regions of the Clarke error grid,
      demonstrating a high degree of accuracy of the unified signal. When tested in an
      implanted array of glucose sensors, a median-based technique (ZMAD) yields an
      accurate unified signal, and its accuracy is superior to signal averaging.

PMID- 14709197
TI  - Modeling beta-cell insulin secretion--implications for closed-loop glucose
      homeostasis.
AB  - Glucose sensing and insulin delivery technology can potentially be linked to form
      a closed-loop insulin delivery system. Ideally, such a system would establish
      normal physiologic glucose profiles. To this end, a model of beta-cell secretion
      can potentially provide insight into the preferred structure of the insulin
      delivery algorithm. Two secretion models were evaluated for their ability to
      describe plasma insulin dynamics during hyperglycemic clamps (humans; n=7), and
      for their ability to establish and maintain fasting euglycemia under conditions
      simulated by the minimal model. The first beta-cell model (SD) characterized
      insulin secretion as a static component that had a delayed response to glucose,
      and a dynamic component that responded to the rate of increase of glucose. The
      second model (PID) described the response in terms of a proportional component
      without delay, an integral component that adjusted basal delivery in proportion
      to hyper/hypoglycemia, and a derivative component that responded to the rate of
      glucose change. Both models fit the beta-cell response during the clamp, and
      established fasting euglycemia under simulated closed-loop conditions; however,
      the SD model did not maintain euglycemia following simulated changes in insulin
      sensitivity or glucose appearance, whereas the PID model did. The PID model was
      more stable under the simulated closed-loop conditions. Both the SD and PID
      models described beta-cell secretion in response to a rapid increase in glucose.
      However, the PID model could maintain fasting euglycemia and was more stable
      under closed-loop conditions, and thus is more suited for such conditions.

PMID- 14709198
TI  - A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive
      insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8).
AB  - In a pilot study, the metabolic effects of continuous subcutaneous insulin
      infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at
      diagnosis in patients with Type 1 diabetes and continued for a 2-year period were
      evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean
      +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs.
      ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight.
      CSII was started immediately after admission to the hospital. Parameters of
      metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were
      evaluated for a 2-year follow-up period. Data are presented for a total of 19
      patients who remained in the study for its duration. Two years after diagnosis,
      mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups,
      respectively (p=not significant). Compared with baseline values, an increase of
      baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was
      observed; however, the difference between the groups was not significant. The
      insulin requirement for the entire duration of the study, but not at entry and 3
      months, was significantly higher in CSII compared with ISIT patients (0.62 +/-
      0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial
      completion patients on CSII continued with this mode of therapy. Implementation
      of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2
      years thereafter achieved similar and optimal metabolic control, but more insulin
      was required with the CSII group. Both types of intensive insulin therapy
      combined with NA are able to preserve C-peptide secretion or even increase
      baseline levels for up to 2 years after diagnosis.

PMID- 14709199
TI  - Unique approach to derivation of random error in laboratory assays: application
      to glycohemoglobin testing demonstrates poor clinical performance for
      immunochemistry assay.
AB  - The measurement of glycohemoglobin is the best measure of mean glucose within a 3
      4 month range. As it is used for patient education, counseling, feedback control,
      and ultimately for patient motivation, its measurement should be optimally
      accurate and precise. Duplicate hemoglobin A1c readings were used to determine
      physiological (changes over time between measurements) and analytic variation of
      two widely used laboratory assays: Bio-Rad Variant II's high-performance liquid
      chromatography (HPLC) system and Roche's immunoassay. The average variation of
      grouped duplicates was calculated and graphed against corresponding time
      intervals. Regression to the y-intercept (0 day separation between readings) was
      used to determine the analytic variation. Analytic coefficients of variation
      (CVs) for the HPLC and immunoassay were determined as 2.6% and 5.1%,
      respectively. The CV of the immunoassay method exceeds physiologically
      established limits of 2-3% and those of the National Glycohemoglobin
      Standardization Program (3-4%). The Bio-Rad HPLC system produces a CV within
      these limits.

PMID- 14709200
TI  - The importance of precision for hemoglobin A1c measurement.

PMID- 14709201
TI  - Alternative site blood glucose testing: a multicenter study.
AB  - The aim of this study was to compare glucose measurements between fingertip and
      forearm using the blood glucose (BG) monitoring system One Touch Ultra
      (LifeScan), an electrochemical sensor that requires only a very small drop of
      blood (1 microL). Patients with type 1 or type 2 diabetes were identified in five
      outpatient diabetes clinics. Participants were requested to use the One Touch
      Ultra at home for 1 week for the measurement of BG levels from both sites.
      Patients filled in a questionnaire about their experience with testing blood
      samples from fingertip and forearm. The agreement between the measurements from
      the two sites was assessed using linear regression analysis, mean absolute
      relative error (MARE), the Bland-Altman method, and Error Grid Analysis (EGA).
      Overall, 112 patients were recruited, of whom 58% had type 1 diabetes. Linear
      regression analysis showed an intercept of 17.7, statistically different from 0
      (p<0.0001). The slope was 0.956, and the Pearson correlation coefficient was
      0.95. A MARE of 12.1% (SD=11.8%) was obtained, with a greater deviation of the
      forearm values from the fingertip ones in the hypoglycemic range (MARE=22.3%;
      SD=21.7%). The Bland-Altman bias plot showed a mean bias of 10.2 mg/dL (SD=23.1),
      with no correlation between mean difference and average BG levels (r=0.02). The
      EGA showed that 89.2% of the values fell in zone A, 10.4% in zone B, and 0.4% in
      zone C. The vast majority of patients (71%) declared that the collection of blood
      from the forearm caused no pain or less pain than the traditional site. Only 17%
      of the patients declared that it was impossible to obtain any blood from the
      forearm, while 63% reported with satisfaction that the quantity requested was
      small. At the end of the study period, 32% of the participants indicated the
      forearm as the preferred test site. Alternative site testing on the arm, with a
      BG meter that requires only a very small drop of blood, is feasible and reliable
      under routine clinical conditions. When testing with the express purpose of
      detecting hypoglycemia, the finger still remains the recommended test site.

PMID- 14709202
TI  - "Sweet Talk": text messaging support for intensive insulin therapy for young
      people with diabetes.
AB  - Optimal diabetes management involves considerable behavioural modification, while
      nonadherence contributes significantly to poor glycaemia. Extensive research on
      psychological interventions aiming to improve glycaemia suggests that current
      strategies are costly and time-consuming and in our experience do not appeal to
      young people with Type 1 diabetes. Text messaging has rapidly become a socially
      popular form of communication. It is personal, highly transportable, and widely
      used, particularly in the adolescent population. However, text messaging coupled
      with specific behavioural health strategies has yet to be utilised effectively.
      We have developed a novel support network ("Sweet Talk"), based on a unique text
      messaging system designed to deliver individually targeted messages and general
      diabetes information. Individualised motivation strategies--based on social
      cognition theory, the health belief model, and goal setting--form the theoretical
      basis of the message content. Intensifying insulin therapy and increasing contact
      with the diabetes team can improve control, but are difficult to provide within
      existing resources. Our support system offers a means of contact and support
      between clinic visits and aims to increase adherence with intensive insulin
      regimens and to improve clinical outcome.

PMID- 14709203
TI  - Diabetes Patient Tracker, a personal digital assistant-based diabetes management
      system for primary care practices in Oklahoma.
AB  - It has been demonstrated that electronic patient registries combined with a
      clinical decision support system have a significant positive impact on the
      documentation and delivery of services provided by health care professionals.
      While implementation of available commercial systems has not always been proven
      effective in a number of primary care practices, development and implementation
      of such a system in a practice-based research network might enhance successful
      implementation. Physicians in our practice-based research network (Oklahoma
      Physicians Resource/Research Network) initiated a project that aimed at
      designing, testing, and implementing a personal digital assistant-based diabetes
      management system. We utilized the "best practice" approach to determine the
      principles on which the application must operate. System development and beta
      testing were also accomplished based on the direct feedback of user clinicians.
      Practice Enhancement Assistants (PEAs) were available in the practices for
      assistance with implementation. Implementation of the Diabetes Patient Tracker
      (DPT) resulted in a significant improvement (p<0.05) in nine of 10 diabetic
      quality of care measures compared with pre-intervention levels in 20 primary care
      practices. Regular PEA visits similarly increased the number of foot exams and
      retinal exams performed in the last year (p=0.03 and 0.02, respectively). DPT is
      a low-cost, feasible, easily implementable, and very effective paper-less tool
      that significantly improves patient care and documentation in primary care
      practices.

PMID- 14709204
TI  - MINMOD Millennium: a computer program to calculate glucose effectiveness and
      insulin sensitivity from the frequently sampled intravenous glucose tolerance
      test.
AB  - The Bergman Minimal Model enables estimation of two key indices of
      glucose/insulin dynamics: glucose effectiveness and insulin sensitivity. In this
      paper we describe MINMOD Millennium, the latest Windows-based version of minimal
      model software. Extensive beta testing of MINMOD Millennium has shown that it is
      user-friendly, fully automatic, fast, accurate, reproducible, repeatable, and
      highly concordant with past versions of MINMOD. It has a simple interface, a
      comprehensive help system, an input file editor, a file converter, an intelligent
      processing kernel, and a file exporter. It provides publication-quality charts of
      glucose and insulin and a table of all minimal model parameters and their error
      estimates. In contrast to earlier versions of MINMOD and some other minimal model
      programs, Millennium provides identified estimates of insulin sensitivity and
      glucose effectiveness for almost every subject.

PMID- 14709205
TI  - Newborn screening and type 1 diabetes: historical perspective and current
      activities at the CDC Division of Laboratory Sciences.

PMID- 14709206
TI  - Predicting energy expenditure of physical activity using hip- and wrist-worn
      accelerometers.
AB  - To investigate the association between physical activity and health, we need
      accurate and detailed free-living physical activity measurements. The
      determination of energy expenditure of activity (EEACT) may also be useful in the
      treatment and maintenance of nutritional diseases such as diabetes mellitus.
      Minute-to-minute energy expenditure during a 24-h period was measured in 60
      sedentary normal female volunteers (35.4 +/- 9.0 years, body mass index 30.0 +/-
      5.9 kg/m2), using a state-of-the-art whole-room indirect calorimeter. The
      activities ranged from sedentary deskwork to walking and stepping at different
      intensities. Body movements were simultaneously measured using a hip-worn
      triaxial accelerometer (Tritrac-R3D, Hemokentics, Inc., Madison, Wisconsin) and a
      wrist-worn uniaxial accelerometer (ActiWatch AW64, MiniMitter Co., Sunriver,
      Oregon) on the dominant arm. Movement data from the accelerometers were used to
      develop nonlinear prediction models (separately and combined) to estimate EEACT
      and compared for accuracy. In a subgroup (n=12), a second 24-h study period was
      repeated for cross-validation of the combined model. The combined model, using
      Tritrac-R3D and ActiWatch, accurately estimated total EEACT (97.7 +/- 3.2% of the
      measured values, p=0.781), as compared with using ActiWatch (86.0 +/- 4.7%,
      p<0.001) or Tritrac-R3D (90.0 +/- 4.6%, p<0.001) alone. This model was also
      accurate for all intensity categories during various physical activities. The
      subgroup cross-validation also showed accurate and reproducible predictions by
      the combination model. In this study, we demonstrated that movement measured
      using accelerometers at the hip and wrist could be used to accurately predict
      EEACT of various types and intensity of activities. This concept can be extended
      to develop valid models for the accurate measurement of free-living energy
      metabolism in clinical populations.

PMID- 14709207
TI  - Actigraphy as metabolic ethography: measuring patterns of physical activity and
      energy expenditure.

PMID- 14709216
TI  - Why doesn't everyone use it?

PMID- 14709217
TI  - Effect of blended CO2 and erbium:YAG laser irradiation on normal and keloid
      fibroblasts: a serum-free study.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of combined CO2
      and Er:YAG laser irradiation on normal (NF) and keloid (KF) facial dermal
      fibroblast production of TGF-beta1 and bFGF. BACKGROUND DATA: Keloids produce
      excess collagen. TGF-beta1 is integral to the growth and stimulation of
      fibroblasts and collagen; bFGF inhibits collagen synthesis. TGF-beta1 and bFGF
      production influence wound healing and may be manipulated by laser irradiation.
      MATERIALS AND METHODS: Human normal fibroblasts (NF) and keloid fibroblasts (KF)
      (2 x 10(4) cells/mL in serum-free media) were exposed to 1.7 J/pulse Er:YAG laser
      energy and CO2 delivered at either 3 or 5 W and at a duty cycle of 25%, 50%, or
      100%. TGF-beta1 and bFGF were assayed using a quantitative ELISA. RESULTS: KF
      demonstrated a statistically significant mean population doubling time (PDT) when
      compared with NF (p=0.01). Irradiated KF and NF had longer PDTs than controls.
      All NF, excluding one irradiated group, and the three KF treated with 3 W
      secreted more bFGF than controls. Irradiated KF secreted less TGF-beta1 than
      controls. Significance was reached with the two groups exposed to 3 W at a duty
      cycle of 25% and 50% (p=0.04 and 0.05, respectively). All irradiated NF secreted
      less TGF-beta1 than controls. CONCLUSION: The combined CO2 and Er:YAG laser
      increased the release of bFGF, which has been shown to promote tightly organized
      collagen bundles, and decreased the concentration of TGF-beta1, which has also
      been shown to promote fibrosis formation. This laser may have a future role in
      keloid treatment, as well as normal facial scar prevention.

PMID- 14709218
TI  - Histopathological changes in dental pulp irradiated by Er:YAG laser: a
      preliminary report on laser pulpotomy.
AB  - OBJECTIVE: The effects of Er:YAG laser irradiation on the pulp tissue during a
      pulpotomy procedure were evaluated histopathologically. BACKGROUND DATA: The
      effects on pulp tissue during laser pulpotomy using Er:YAG laser irradiation are
      not clear. MATERIALS AND METHODS: Sixty mesial root canals of mandibular first
      molars in rats were divided into four groups. In three of these groups, root
      canals were irradiated using an Er:YAG laser at 2 Hz and 34, 68, and 102 mJ/pulse
      for 15 sec. Non-irradiated canals served as controls. The effects of laser
      irradiation on the remaining pulp tissue and periodontal tissues were evaluated
      at 0 days, 2 days, and 1 week after irradiation under light microscopy. RESULTS:
      At 1 week after treatment, no inflammation or resorption was observed in any
      cases in the control or 34 mJ/pulse-irradiated groups. However, moderate to
      severe inflammation was observed in 9 of 10 cases (90%) in the 68 and 102
      mJ/pulse-irradiated groups. CONCLUSION: These results suggest that effects on
      pulp tissues during a pulpotomy procedure by Er:YAG laser irradiation are
      minimal, if appropriate parameters are selected, and this is a potential therapy
      for pulpotomy of human teeth.

PMID- 14709219
TI  - Low-intensity near-infrared laser radiation-induced changes of
      acetylcholinesterase activity of human erythrocytes.
AB  - OBJECTIVE: The aim of the present study was to investigate the transformations of
      red blood cells produced by low-intensity infrared laser radiation (810 nm).
      BACKGROUND DATA: Low-intensity (the output power of a laser device in the
      milliwatt range) laser radiation as a local phototherapeutic modality is
      characterized by its ability to induce non-thermic, nondestructive
      photobiological processes in cells and tissues. However, the exact theory
      concerning the therapeutic effects of laser biostimulation has not been
      developed. MATERIALS AND METHODS: The suspensions of human erythrocytes in PBS
      (10% hematocrit) were irradiated with near-infrared (810 nm) therapy laser at
      different light doses (0-20 J) and light power (fluence rate; 200 or 400 mW) at
      37 degrees C. As the parameters characterizing the cell structural and functional
      changes membrane acetylcholinesterase (AchEase) activity, the membrane potential,
      the level of intracellular glutathione, the level of products of membrane lipid
      peroxidation, and the cell osmotic stability were measured. RESULTS: It was found
      that near-infrared low-intensity laser radiation produced complex biphasic dose
      dependent changes of the parameters of AchEase reaction in the dose-dependent
      manner: at smaller doses of radiation (6 J) the maximal reaction rate and
      Michaelis-Menten constant value decreased, and at higher radiation doses these
      parameters increased. No significant changes of erythrocyte stability, cellular
      redox state (reduced glutathione or lipid peroxidation product levels), or cell
      membrane electrochemical potential were observed. CONCLUSION: Low-intensity near
      infrared laser radiation (810 mn) produced AchEase activity changes, reflecting
      the effect of light on the enzyme due to energy absorption. Protein molecule
      conformational transitions and enzyme activity modifications in cells have been
      suggested as laser radiation-induced events.

PMID- 14709220
TI  - Degree of conversion of composite resin: a Raman study.
AB  - OBJECTIVE: Near infrared Raman spectroscopy (RS) was used to monitor, in vitro,
      the degree of conversion (DC) of composite resins (Z100, 3M), photoactivated by
      both the halogen lamp and the argon laser beam. BACKGROUND DATA: Several methods
      were used to study the alterations of composite resins. Vibration methods such as
      RS allow a precise assessment of the depth of polymerization and the degree of
      conversion of composite resins. MATERIALS AND METHODS: Sixty circular blocks of
      resin (7 mm x 2.5 mm) were cured using a halogen light source (n=30, lambda=400
      500 nm, power density=478 mW/cm2) or an argon laser beam (n=30, lambda=488 nm,
      power density=625 mW/cm2) using the same irradiation time (5, 10, 20, 30, 40, and
      60 sec). The directly irradiated (top) and the non-irradiated (bottom) surfaces
      were analyzed immediately after curing by Raman spectroscopy. RESULTS: The Raman
      results show systematic changes of the relative intensities between the peaks at
      1610 (aromatic C=C stretching mode) and the 1640 cm(-1) (methacrylate C=C
      stretching mode), as a function of irradiation time. After 60 sec of irradiation
      time, the maximum degree of conversion reached for the samples cured either by
      the argon laser or halogen lamp was 66.4% and 62.2%, respectively. CONCLUSION:
      The argon laser was more effective and showed better biocompatibility, with less
      residual monomer in the bottom (2.5 mm). These results show that RS can be used
      as an effective method to study the degree of conversion of composite resins.

PMID- 14709221
TI  - Usefulness of low-level laser for control of painful stomatitis in patients with
      hand-foot-and-mouth disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of low-level
      laser therapy (LLLT) for the control of painful stomatitis in patients with hand
      foot-and-mouth disease (HFMD). BACKGROUND DATA: LLLT has been successfully
      applied to various painful oral mucosal diseases, although there have been few
      reports on LLLT for HFMD patients. MATERIALS AND METHODS: Through a randomized
      double-blind placebo controlled trial, the painful period of HFMD stomatitis was
      compared between the LLLT group (n=11) and the placebo LLLT one (n=9), which had
      similar clinical backgrounds. The LLLT parameters supplied were as follows:
      wavelength of 830 nm, power of 30 mW, frequency of 30 Hz, and energy output of
      1.1 J/cm2. Acceptability and safety of the treatment were also evaluated.
      RESULTS: The painful period was shorter in the LLLT group (4.0 +/- 1.3 days) than
      in the placebo LLLT one (6.7 +/- 1.6 days) with a statistically significant
      difference (p<0.005). The treatment was judged acceptable for 90.0% (18 of 20) of
      patients. No adverse events were observed in any cases. CONCLUSION: LLLT is a
      useful method to control HFMD stomatitis by shortening the painful period, with
      its high acceptability and lack of adverse events.

PMID- 14709222
TI  - Prevention of dental caries in partially erupted permanent teeth with a CO2
      laser.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of CO2 laser
      irradiation in the prevention of pit and fissure caries in immature molars with
      covering opercula. BACKGROUND DATA: In pediatric dentistry, it is not unusual to
      find partially erupted immature permanent teeth, especially with opercula.
      Conventional dental caries prevention is not effective in these cases because of
      the immaturity of tooth substance and the presence of the opercula, which
      accumulate a substantial amount of plaque. MATERIALS AND METHODS: The CO2 laser
      was used on 22 immature erupting molars with opercula. In each case, we first cut
      the operculum with a CO2 laser in a 2- or 3-watt continuous mode. Then, the
      occlusal surface was irradiated spot by spot along the pits and fissures of the
      molar using a CO2 laser in a 2-watt pulsed mode with 0.2 sec of irradiation time
      (average power, 0.3 watt; pulse width, 10 msec; repetition time, 15 Hz; energy
      density, 15 J/cm2). Each of the studied teeth was clinically examined for dental
      caries for 3 years. RESULTS: It took less than 2 min to cut the operculum, and
      there was no bleeding. The irradiation imparted acid resistance to the teeth
      without any discomfort to the patients. The patients did not complain of any pain
      after the procedure. Only two of the studied teeth developed dental caries during
      the observation period. CONCLUSION: We conclude that a CO2 laser might be an
      effective mode of treatment in the prevention of pit and fissure caries in
      partially erupted permanent molars covered with opercula.

PMID- 14709223
TI  - Laser-induced temperature changes in dentine.
AB  - OBJECTIVE: The purpose of this work is to study the temperature rise and
      potential thermal damage caused during ablation of human dentine using a super
      pulsed carbon dioxide laser of 9.6-microm wavelength, equipped with a water
      cooling spray and scanner system. BACKGROUND DATA: There have been no reports on
      thermal effects of super pulsed CO2 laser of 9.6 microm wavelength on human
      dentine recently. MATERIALS AND METHODS: Two different types of samples were
      investigated to yield data most consistent with a typical clinical situation.
      Human dentine slices and crown segments were studied at a drilling depth of 1.0
      +/- 0.1 mm and 2.5 +/- 0.5 mm, respectively. A control group treated with a
      conventional hand piece was compared to four laser groups with settings varying
      from 2 to 8 W. RESULTS: In the laser group demonstrating the highest elevation in
      temperature of the four studied, dentine slices lased at 2 W for 15 sec showed a
      mean temperature rise of less than 1.68 degrees C at an ablation rate of 0.86 +/-
      0.08 mm. Conventional drilling with a comparable ablation rate of 0.76 +/- 0.59
      mm resulted in a mean rise of 2.87 degrees C. The laser groups of crown segments
      revealed a constant decrease in temperature. SEM observations were lacking the
      typical morphological changes seen in earlier studies, specifically extensive
      melting, charring or cracking. CONCLUSION: A maximum rise of mean temperature to
      1.68 degrees C in closest vicinity to the pulpal chamber and the morphological
      unaltered dentine surfaces demonstrate the safe and tissue preserving character
      of the superpulsed 9.6 microm CO2 laser. The laser caused an even lower
      temperature rise than conventional drilling. Moreover, the laser showed
      acceptable efficacy with ablation rates that did not significantly differ from
      the conventional dental drill.

PMID- 14709226
TI  - Laser literature watch.

PMID- 14709224
TI  - Effect of 830-nm laser light on the repair of bone defects grafted with inorganic
      bovine bone and decalcified cortical osseous membrane.
AB  - OBJECTIVE: The aim of this study was to assess histologically the effect of LLLT
      (lambda830 nm) on the repair of standardized bone defects on the femur of Wistar
      albinus rats grafted with inorganic bovine bone and associated or not to
      decalcified bovine cortical bone membrane. BACKGROUND DATA: Bone loss may be a
      result of several pathologies, trauma or a consequence of surgical procedures.
      This led to extensive studies on the process of bone repair and development of
      techniques for the correction of bone defects, including the use of several types
      of grafts, membranes and the association of both techniques. There is evidence in
      the literature of the positive effect of LLLT on the healing of soft tissue
      wounds. However, its effect on bone is not completely understood. MATERIALS AND
      METHODS: Five randomized groups were studied: Group I (Control); Group IIA (Gen
      ox); Group IIB (Gen-ox + LLLT); Group IIIA (Gen-ox + Gen-derm) and Group IIIB
      (Gen-ox + Gen-derm + LLLT). Bone defects were created at the femur of the animals
      and were treated according to the group. The animals of the irradiated groups
      were irradiated every 48 h during 15 days; the first irradiation was performed
      immediately after the surgical procedure. The animals were irradiated
      transcutaneously in four points around the defect. At each point a dose of 4
      J/cm2 was given (phi approximately 0.6 mm, 40 mW) and the total dose per session
      was 16 J/cm2. The animals were humanely killed 15, 21, and 30 days after surgery.
      The specimens were routinely processed to wax, serially cut, and stained with H&E
      and Picrosirius stains and analyzed under light microscopy. RESULTS: The results
      showed evidence of a more advanced repair on the irradiated groups when compared
      to non-irradiated ones. The repair of irradiated groups was characterized by both
      increased bone formation and amount of collagen fibers around the graft within
      the cavity since the 15th day after surgery, through analysis of the
      osteoconductive capacity of the Gen-ox and the increment of the cortical repair
      in specimens with Gen-derm membrane. CONCLUSION: It is concluded that LLLT had a
      positive effect on the repair of bone defect submitted the implantation of graft.

PMID- 14709227
TI  - Neural mechanisms for response selection: representation specific or modality
      independent?

PMID- 14709228
TI  - Common neural substrates for response selection across modalities and mapping
      paradigms.
AB  - In many situations, people can only compute one stimulus-to-response mapping at a
      time, suggesting that response selection constitutes a "central processing
      bottleneck" in human information processing. Using fMRI, we tested whether common
      or distinct brain regions were involved in response selection across visual and
      auditory inputs, and across spatial and nonspatial mapping rules. We isolated
      brain regions involved in response selection by comparing two conditions that
      were identical in perceptual input and motor output, but differed in the
      complexity of the mapping rule. In the visual-manual task of Experiment 1, four
      vertical lines were positioned from left to right, and subjects pressed one of
      four keys to report which line was unique in length. In the auditory-manual task
      of Experiment 2, four tones were presented in succession, and subjects pressed
      one of four keys to report which tone was unique in duration. For both visual and
      auditory tasks, the mapping between target position and key position was either
      spatially compatible or incompatible. In the verbal task of Experiment 3,
      subjects used nonspatial mappings that were either compatible ("same" if colors
      matched; "different" if they mismatched) or incompatible (the opposite).
      Extensive activation overlap was observed across all three experiments for
      incompatible versus compatible mapping in bilateral parietal and frontal regions.
      Our results indicate that common neural substrates are involved in response
      selection across input modalities and across spatial and nonspatial domains of
      stimulus-to-response mapping, consistent with behavioral evidence that response
      selection is a central process.

PMID- 14709229
TI  - Common neural mechanisms for response selection and perceptual processing.
AB  - Behavioral evidence supports a dissociation between response selection (RS;
      stimulus-to-response [S-R] mapping) and perceptual discrimination (PD): The
      former may be subject to a central processing bottleneck, whereas the latter is
      not (Pashler, 1994). We previously (Jiang & Kanwisher, 2003) identified a set of
      frontal and parietal regions involved in RS as those that produce a stronger
      signal when subjects follow a difficult S-R mapping rule than an easy mapping
      rule. Here, we test whether any of these regions are selectively activated by RS
      and not perceptual processing, as predicted by the central bottleneck view. In
      Experiment 1, subjects indicated which of four parallel lines was unique in
      length; PD was indexed by a higher BOLD response when the discrimination was
      difficult versus easy. Stimuli and responses were closely matched across
      conditions. We found that all regions-of-interest (ROIs) engaged by RS were also
      engaged by perceptual processing, arguing against the existence of mechanisms
      exclusively involved in RS. In Experiments 2 and 3, we asked what processes might
      go on in these ROIs, such that they could be recruited by both RS and perceptual
      processing. Our data argue against an account of this common activation in terms
      of spatial processing or general task difficulty. Thus, PD may recruit the same
      central processes that are engaged by RS.

PMID- 14709230
TI  - Neural evidence for representation-specific response selection.
AB  - Response selection is the mental process of choosing representations for
      appropriate motor behaviors given particular environmental stimuli and one's
      current task situation and goals. Many cognitive theories of response selection
      postulate a unitary process. That is, one central response-selection mechanism
      chooses appropriate responses in most, if not all, task situations. However,
      neuroscience research shows that neural processing is often localized based on
      the type of information processed. Our current experiments investigate whether
      response selection is unitary or stimulus specific by manipulating response
      selection difficulty in two functional magnetic resonance imaging experiments
      using spatial and nonspatial stimuli. The same participants were used in both
      experiments. We found spatial response selection involves the right prefrontal
      cortex, the bilateral premotor cortex, and the dorsal parietal cortical regions
      (precuneus and superior parietal lobule). Nonspatial response selection,
      conversely, involves the left prefrontal cortex and the more ventral posterior
      cortical regions (left middle temporal gyrus, left inferior parietal lobule, and
      right extrastriate cortex). Our brain activation data suggest a cognitive model
      for response selection in which different brain networks mediate the choice of
      appropriate responses for different types of stimuli. This model is consistent
      with behavioral research suggesting that response-selection processing may be
      more flexible and adaptive than originally proposed.

PMID- 14709231
TI  - Working memory for complex scenes: age differences in frontal and hippocampal
      activations.
AB  - Age differences in frontal and hippocampal activations in working memory were
      investigated during a maintenance and subsequent probe interval in an event
      related fMRI design. Younger and older adults either viewed or maintained
      photographs of real-world scenes (extended visual or maintenance conditions) over
      a 4-sec interval before responding to a probe fragment from the studied picture.
      Behavioral accuracy was largely equivalent across age and conditions on the probe
      task, but underlying neural activations differed. Younger but not older adults
      showed increased left anterior hippocampal activations in the extended visual
      compared with the maintenance condition. On the subsequent probe interval,
      however, older adults showed more left and right inferior frontal activations
      than younger adults. The increased frontal activations at probe in older adults
      may have been compensatory for the decreased hippocampal activations during
      maintenance, but alternatively could have reflected the increased difficulty of
      the probe task for the older subjects. Thus, we demonstrate qualitatively
      different engagement of both frontal and hippocampal structures in older adults
      in a working memory task, despite behavioral equivalence.

PMID- 14709232
TI  - ERP evidence for a sex-specific Stroop effect in emotional speech.
AB  - The present study investigated the interaction of emotional prosody and word
      valence during emotional comprehension in men and women. In a prosody-word
      interference task, participants listened to positive, neutral, and negative words
      that were spoken with a happy, neutral, and angry prosody. Participants were
      asked to rate word valence while ignoring emotional prosody, or vice versa.
      Congruent stimuli were responded faster and more accurately as compared to
      incongruent emotional stimuli. This behavioral effect was more salient for the
      word valence task than for the prosodic task and was comparable between men and
      women. The event-related potentials (ERPs) revealed a smaller N400 amplitude for
      congruent as compared to emotionally incongruent stimuli. This ERP effect,
      however, was significant only for the word valence judgment and only for female
      listeners. The present data suggest that the word valence judgment was more
      difficult and more easily influenced by task-irrelevant emotional information
      than the prosodic task in both men and women. Furthermore, although emotional
      prosody and word valence may have a similar influence on an emotional judgment in
      both sexes, ERPs indicate sex differences in the underlying processing. Women,
      but not men, show an interaction between prosody and word valence during a
      semantic processing stage.

PMID- 14709233
TI  - Processing tonal modulations: an ERP study.
AB  - A common stylistic element of Western tonal music is the change of key within a
      musical sequence (known as modulation in musical terms). The aim of the present
      study was to investigate neural correlates of the cognitive processing of
      modulations with event-related brain potentials. Participants listened to
      sequences of chords that were infrequently modulating. Modulating chords elicited
      distinct effects in the event-related brain potentials: an early right anterior
      negativity reflecting the processing of a violation of musical regularities and a
      late frontal negativity taken to reflect processes of harmonic integration.
      Additionally, modulations elicited a tonic negative potential suggested to
      reflect cognitive processes characteristic for the processing of tonal
      modulations, namely, the restructuring of the "hierarchy of harmonic stability"
      (which specifies musical expectations), presumably entailing working memory
      operations. Participants were "nonmusicians"; results thus support the hypothesis
      that nonmusicians have a sophisticated (implicit) knowledge about musical
      regularities.

PMID- 14709234
TI  - An event-related FMRI investigation of implicit semantic priming.
AB  - The neural basis underlying implicit semantic priming was investigated using
      event-related fMRI. Prime-target pairs were presented auditorily for lexical
      decision (LD) on the target stimulus, which was either semantically related or
      unrelated to the prime, or was a nonword. A tone task was also administered as a
      control. Behaviorally, all participants demonstrated semantic priming in the LD
      task. fMRI results showed that for all three conditions of the LD task,
      activation was seen in the superior temporal gyrus (STG), the middle temporal
      gyrus (MTG), and the inferior parietal lobe, with greater activation in the
      unrelated and nonword conditions than in the related condition. Direct
      comparisons of the related and unrelated conditions revealed foci in the left
      STG, left precentral gyrus, left and right MTGs, and right caudate, exhibiting
      significantly lower activation levels in the related condition. The reduced
      activity in the temporal lobe suggests that the perception of the prime word
      activates a lexical-semantic network that shares common elements with the target
      word, and, thus, the target can be recognized with enhanced neural efficiency.
      The frontal lobe reductions most likely reflect the increased efficiency in
      monitoring the activation of lexical representations in the temporal lobe, making
      a decision, and planning the appropriate motor response.

PMID- 14709235
TI  - Orienting attention to locations in internal representations.
AB  - Three experiments investigated whether it is possible to orient selective spatial
      attention to internal representations held in working memory in a similar fashion
      to orienting to perceptual stimuli. In the first experiment, subjects were either
      cued to orient to a spatial location before a stimulus array was presented (pre
      cue), cued to orient to a spatial location in working memory after the array was
      presented (retro-cue), or given no cueing information (neutral cue). The stimulus
      array consisted of four differently colored crosses, one in each quadrant. At the
      end of a trial, a colored cross (probe) was presented centrally, and subjects
      responded according to whether it had occurred in the array. There were
      equivalent patterns of behavioral costs and benefits of cueing for both pre-cues
      and retro-cues. A follow-up experiment used a peripheral probe stimulus requiring
      a decision about whether its color matched that of the item presented at the same
      location in the array. Replication of the behavioral costs and benefits of pre
      cues and retro-cues in this experiment ruled out changes in response criteria as
      the only explanation for the effects. The third experiment used event-related
      potentials (ERPs) to compare the neural processes involved in orienting attention
      to a spatial location in an external versus an internal spatial representation.
      In this task, subjects responded according to whether a central probe stimulus
      occurred at the cued location in the array. There were both similarities and
      differences between ERPs to spatial cues toward a perception versus an internal
      spatial representation. Lateralized early posterior and later frontal
      negativities were observed for both pre- and retro-cues. Retro-cues also showed
      additional neural processes to be involved in orienting to an internal
      representation, including early effects over frontal electrodes.

PMID- 14709236
TI  - Grammar processing outside the focus of attention: an MEG study.
AB  - To address the cerebral processing of grammar, we used whole-head high-density
      magnetoencephalography to record the brain's magnetic fields elicited by
      grammatically correct and incorrect auditory stimuli in the absence of directed
      attention to the stimulation. The stimuli were minimal short phrases of the
      Finnish language differing only in one single phoneme (word-final inflectional
      affix), which rendered them as either grammatical or ungrammatical. Acoustic and
      lexical differences were controlled for by using an orthogonal design in which
      the phoneme's effect on grammaticality was inverted. We found that occasional
      syntactically incorrect stimuli elicited larger mismatch negativity (MMN)
      responses than correct phrases. The MMN was earlier proposed as an index of
      preattentive automatic speech processing. Therefore, its modulation by
      grammaticality under nonattend conditions suggests that early syntax processing
      in the human brain may take place outside the focus of attention. Source analysis
      (single-dipole models and minimum-norm current estimates) indicated
      grammaticality dependent differential activation of the left superior temporal
      cortex suggesting that this brain structure may play an important role in such
      automatic grammar processing.

PMID- 14709237
TI  - Direct evidence for a binding between cognitive and motor functions in humans: a
      TMS study.
AB  - During voluntary motor actions, the cortico-spinal (CS) excitability is known to
      be modulated, on the one hand by cognitive (intention-related) processes and, on
      the other hand, by motor (performance-related) processes. Here, we studied the
      way these processes interact in the tuning of CS excitability during voluntary
      wrist movement. We used transcranial magnetic stimulation (TMS) both as a
      reliable tool for quantifying the CS excitability, through the motor-evoked
      potentials (MEPs), and as a central perturbation evoking a movement (because the
      stimulation intensity was above threshold) with subjects instructed to prepare
      (without changing their muscle activation) either to "let go" or to "resist" to
      this evoked movement. We studied the simultaneous evolution of both the motor
      performance and the MEPs in the wrist flexor and extensor, separately for the
      successful trials (on average, 66% of the trials whatever the condition) and the
      unsuccessful trials; this allowed us to dissociate the intention- and performance
      related processes. To their great surprise, subjects were found able to
      cognitively prepare themselves to resist a TMS-induced central perturbation; they
      all reported an important cognitive effort on the evoked movement. Moreover,
      because TMS only evoked short-latency MEPs (and no long-latency components), the
      amplitude of these short-latency MEPs was found to be related in a continuous way
      to the actual movement whatever the prior intention. These results demonstrate
      that prior intention allows an anticipatory modulation of the CS excitability,
      which is not only selective (as already known) but also efficient, giving the
      intended motor behavior a real chance to be realized. This constitutes a direct
      evidence of the role of the CS excitability in the binding between cognitive and
      motor processes in humans.

PMID- 14709238
TI  - A monotonic code for sound azimuth in primate inferior colliculus.
AB  - We investigated the format of the code for sound location in the inferior
      colliculi of three awake monkeys (Macaca mulatta). We found that roughly half of
      our sample of 99 neurons was sensitive to the free-field locations of broadband
      noise presented in the frontal hemisphere. Such neurons nearly always responded
      monotonically as a function of sound azimuth, with stronger responses for more
      contralateral sound locations. Few, if any, neurons had circumscribed receptive
      fields. Spatial sensitivity was broad: the proportion of the total sample of
      neurons responding to a sound at a given location ranged from 30% for ipsilateral
      locations to 80% for contralateral locations. These findings suggest that sound
      azimuth is represented via a population rate code of very broadly responsive
      neurons in primate inferior colliculi. This representation differs in format from
      the place code used for encoding the locations of visual and tactile stimuli and
      poses problems for the eventual convergence of auditory and visual or
      somatosensory signals. Accordingly, models for converting this representation
      into a place code are discussed.

PMID- 14709240
TI  - Precise oculomotor correlates of visuospatial mental rotation and circular motion
      imagery.
AB  - Visual imagery is a basic form of cognition central to activities such as problem
      solving or creative thinking. Phenomena such as mental rotation, in which mental
      images undergo spatial transformations, and motion imagery, in which we imagine
      objects in motion, are very elusive. For example, although several aspects of
      visual imagery and mental rotation have been reconstructed through mental
      chronometry, their instantaneous evolution has never been directly observed. We
      paired mental chronometry to eye movement recording in subjects performing a
      visuospatial mental rotation task and an instructed circular motion imagery task.
      In both tasks, sequences of spontaneous saccades formed curved trajectories with
      a regular spatio-temporal evolution. In the visuospatial mental rotation task,
      saccadic amplitude decreased progressively within each sequence, resulting in an
      average gaze rotation with a bell-shaped asymmetrical angular velocity profile
      whose peak and mean increased with the amount of the to-be-performed rotation, as
      in reaching movements. In the second task, the average gaze rotation reproduced
      faithfully the to-be-imagined constant-velocity circular motion, thus excluding
      important distortions in the oculomotor performance. These findings show for the
      first time the instantaneous spatio-temporal evolution of mental rotation and
      motion imagery. Moreover, the fact that visuospatial mental rotation is modeled
      as a reaching act suggests that reaching pertains to the realm of visuospatial
      thinking, rather than being restricted to the motor domain. This approach based
      on eye movement recording can be profitably coupled to methods such as event
      related potentials, transcranial magnetic stimulation, or functional magnetic
      resonance to study the precise neuronal dynamics associated with an ongoing
      mental activity.

PMID- 14709239
TI  - Spatial and temporal sequence learning in patients with Parkinson's disease or
      cerebellar lesions.
AB  - The functional role of different subcortical areas in sequence learning is not
      clear. In the current study, Parkinson's patients, patients with cerebellar
      damage, and age-matched control participants performed a serial reaction time
      task in which a spatial sequence and a temporal sequence were presented
      simultaneously. The responses were based on the spatial sequence, and the
      temporal sequence was incidental to the task. The two sequences were of the same
      length, and the phase relationship between them was held constant throughout
      training. Sequence learning was assessed comparing performance when both
      sequences were present versus when the dimension of interest was randomized. In
      addition, sequence integration was assessed by introducing phase-shift blocks. A
      functional dissociation was found between the two patient groups. Whereas the
      Parkinson's patients learned the spatial and temporal sequences individually,
      they did not learn the relationship between the two sequences, suggesting the
      basal ganglia play a functional role in sequence integration. In contrast, the
      cerebellar patients did not show any evidence of sequence learning at all,
      suggesting the cerebellum might play a general role in forming sequential
      associations.

PMID- 14709241
TI  - Two percent of HIV-positive U.S. blood donors are infected with non-subtype B
      strains.
AB  - To estimate the prevalence of HIV strains other than the predominant HIV-1B
      subtype in the U.S. blood donor population we genetically and serologically
      characterized HIV in infected blood donations collected throughout he United
      States from 1997 to mid-2000. Using a combination of DNA heteroduplex mobility
      and DNA sequence analyses of the env and gag regions of HIV-1 we determined that
      285 of 312 infections were caused by HIV-1B and six by non-subtype B HIV-1 (four
      HIV-1C, one HIV-1AE, one HIV-1A). Genetic distances of greater than 14% in the
      envelope V3-V5 region of the four HIV-1C strains indicated that they did not
      share a recent common origin. HIV-1 group M, N, and O, and HIV-2 specific peptide
      serological testing of the 20 PCR-negative samples determined that one infection
      was caused by HIV-2 and none by HIV-1 group N and O. The major risk factor for
      infection with a non-HIV-1B strain was sex with an HIV-infected person from
      Africa although three of seven non-HIV-1B-infected subjects did not fit that
      category. For four of seven non-HIV-1B-infected subjects the subtype detected was
      consistent with the African country of origin of the infected person or of their
      sexual partner. The frequency of genetically confirmed non-subtype-B HIV
      infection in a geographically dispersed group of infected U.S. blood donors in
      1977-2000 was therefore 2.0% (6/312).

PMID- 14709242
TI  - Emergence of the HIV type 1 epidemic in the twentieth century: comparing
      hypotheses to evidence.
AB  - The existence of multiple groups of HIV-1 and HIV-2 suggests that zoonotic
      transmissions of SIV have occurred at a low rate for centuries. Hence, an
      increase in the rate of human-to-human transmission may be necessary and
      sufficient to explain the emergence of HIV as an epidemic in the twentieth
      century. Three common hypotheses to explain accelerated transmission are (1)
      social changes accelerated sexual transmission, (2) health care changes
      accelerated parenteral transmission, and (3) serial passaging adapted HIV for
      persistent infection and sexual transmission. These hypotheses can be compared to
      a range of evidence. Temporal and geographic discontinuities in HIV epidemic
      growth are not easily explained by supposed increases in sexual transmission over
      time. Large historic changes in sexual transmission are hard to explain based on
      weak evidence associating HIV prevalence in African communities with differences
      in sexual behavior. On the other hand, documented iatrogenic outbreaks show high
      rates of parenteral transmission. The distribution of hepatitis C virus
      infections and the history of multiinjection treatment for trypanosomiasis in
      Central Africa suggest widespread parenteral transmission of blood-borne viruses
      during 1920-1940, coinciding in time and place with the early HIV epidemic. This
      suggests an important role for parenteral transmission in the early spread of
      HIV. Further research could improve our understanding of the early HIV epidemic.

PMID- 14709243
TI  - SENV infection in HIV-positive patients: prevalence, subtype characterization,
      and impact on HIV disease progression.
AB  - Among 165 HIV-infected patients, prevalence of SEN virus (SENV) infection was
      51.5%, with subtype A predominance and unique SENV variant (67%), but also SENV
      superinfections with multiple variants were frequent. High prevalence,
      superinfection and broad SENV subtype diversification have been demonstrated, all
      linked to intravenous drug use (IVDU) as a risk factor for HIV acquisition. At
      multivariate analysis, SENV infection did not appear to have any negative impact
      on survival, while a possible protective effect needs further investigation.

PMID- 14709245
TI  - HIV Type 1 replication in cerebrospinal fluid of patients with AIDS-related non
      Hodgkin's lymphoma receiving chemotherapy and antiretroviral therapy.
AB  - Chemotherapy for cancer could have negative effects on HIV-1 dynamic in addition
      to the effects on immunological status. At the moment few data are available
      about the effects of chemotherapy on systemic HIV-1 replication, but the effects
      on the central nervous system, considered an independent compartment for viral
      replication, has never been investigated. We studied 19 HIV-1-infected patients
      with non-Hodgkin lymphoma (NHL) treated concomitantly with chemotherapy and
      highly active antiretroviral therapy (HAART) to evaluate HIV-1 replication and
      assess virological response to HAART in cerebrospinal fluid during chemotherapy.
      No patients were diagnosed with lymphoma involvement of the central nervous
      system. In 18 of 19 patients an HIV-1 load below 200 copies/ml was obtained in
      cerebrospinal fluid (CSF) during treatment. A correlation between plasma and CSF
      HIV-1 RNA levels was present at baseline, and was confirmed at the fourth cycle
      of chemotherapy. A significant decline in the mean difference between plasma and
      CSF HIV-1 RNA load was observed when comparing the value at the first cycle of
      chemotherapy with subsequent cycles. HAART even during chemotherapy allows us to
      obtain an effective control of HIV-1 infection in CSF in patients affected by
      NHL. In HIV-infected patients with NHL, the contemporaneous administration of
      HAART and chemotherapy is advisable to obtain a suppression of HIV-1 replication
      in CNS compartment during the potentially immunosuppressing effect of cancer
      treatment.

PMID- 14709244
TI  - Treatment of chronic hepatitis C in HIV-infected patients with interferon alpha
      2b plus ribavirin.
AB  - One hundred six HIV-infected patients with chronic hepatitis C virus (HCV)
      infection were randomized to receive ribavirin (RBV) 400 mg bid plus interferon
      alpha-2b (IFN-alpha) at two different doses, 3 mU tiw (control arm) or 5 mU daily
      for the first 6 weeks, followed by 3 mU tiw until completing 6 months of therapy
      (induction arm). All patients had CD4 counts above 350 cells/microl and 89% were
      taking antiretroviral therapy. Adverse effects leading to treatment
      discontinuation occurred in 12.3% of patients, a rate quite similar to that seen
      in HCV-monoinfected patients. Negative serum HCV-RNA values (< 60 IU/ml) were
      recorded in 24.7% and 35.5% of patients at 3 and 6 months of therapy. However, in
      the intent-to-treat analysis, sustained response was reached by only 16% of
      patients (22.4% in the on-treatment analysis). No differences between treatment
      arms were noticed. Patients with HCV genotypes 2 or 3 had a 7-fold higher
      response rate than those with HCV genotypes 1 or 4. Therefore, early, end-of
      treatment, and sustained response rates are lower in HIV/HCV-coinfected patients
      treated with RBV/IFN-alpha combination therapy. Since HCV-related liver disease
      is currently one of the leading causes of morbidity and mortality among HIV
      infected patients, new treatment options are urgently needed for coinfected
      individuals.

PMID- 14709246
TI  - Peripheral blood Dendritic cells are not a major reservoir for HIV type 1 in
      infected individuals on virally suppressive HAART.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells, and their
      physiological localization in tissues that interact with the external environment
      is important as a first barrier against pathogens such as human immunodeficiency
      virus type I (HIV-1). Several models have been proposed to explain the possible
      role of DCs as a reservoir for HIV-1 in patients on virally suppressive highly
      active antiretroviral therapy (HAART). However, the low yield of cell isolates
      has made this evaluation a difficult task. The present study analyzes whether
      peripheral blood DCs from HIV-1-infected individuals on virally suppressive
      HAART, with plasma HIV-1 RNA levels of less than 50 copies/ml, carry either HIV-1
      provirus and/or HIV-1 virions. Peripheral blood DCs were isolated from a cohort
      of 10 HIV-1-seropositive men taking suppressive HAART. In five patients,
      plasmacytoid and myeloid dendritic cells were isolated to attempt to identify
      their respective roles in HIV-1 residual disease. Viral out-growth assays were
      performed in vitro, as well as gag and R/U5 polymerase chain reaction (PCR)
      amplification of viral RNA and DNA, respectively, from DC and peripheral blood
      mononuclear cell (PBMC) extracts. Fluorescence activated cell-sorting (FACS) data
      revealed cellular yields from 85.90 to 95.18%, of relatively pure DCs isolated
      from patients' PBMCs. Although HIV-1 RNA gag and DNA RU/5 were detected in all
      PBMC samples isolated from the patients, proviral DNA and viral RNA forms were
      not detected in any of the DC isolates. In addition, no replication-competent
      virus was demonstrated in DC coculture assays, while virus was isolated from each
      patients' CD8+ T-lymphocyte-depleted PBMC cocultures. Furthermore, HIV-1 gag
      proviral DNA was not detected in either plasmacytoid or myeloid DC subfractions.
      The current study suggests that in HIV-1-infected individuals treated with
      suppressive HAART, peripheral blood DCs do not carry HIV-1 proviral DNA or viral
      particles attached to their surface. These populations of peripheral blood DCs
      are likely not a major HIV-1 reservoir in patients on HAART with clinically
      undetectable plasma viral RNA.

PMID- 14709247
TI  - Humans have antibodies reactive with Bovine leukemia virus.
AB  - Bovine leukemia virus (BLV) is an oncogenic retrovirus that commonly infects
      cattle and causes B cell leukosis in 1-5% of infected cattle. BLV-infected cells
      are present in marketed beef and dairy products. In the decade after the
      discovery of BLV in 1969, studies using agar gel immunodiffusion and complement
      fixation assays failed to find antibodies to BLV in human sera. This led to the
      prevailing opinion that exposure of humans to BLV and/or the potential for
      infection are not significant and therefore the virus is not a public health
      hazard. We reexamined this issue using more sensitive immunological techniques
      available today. Using immunoblotting to test the sera of 257 humans for
      antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV capsid antigen
      (p24), we detected at least one antibody isotype reactive with BLV in 74% of the
      human sera tested. The specificity of the reactivity was strongly suggested by
      competition studies and by ruling out cross-reacting antibodies to other chronic
      human viruses. Our results suggest that antibodies reactive with the BLV capsid
      antigen may serve as a biomarker for exposure to BLV and this exposure may be
      widespread. The results do not necessarily mean that humans are actually infected
      with BLV; the antibodies could be a response to heat-denatured BLV antigens
      consumed in food. They do, however, suggest that further studies in this area
      could be important.

PMID- 14709248
TI  - Hypermutation of HIV type 1 genomes isolated from infants soon after vertical
      infection.
AB  - Hypermutation involving excessive G-to-A substitutions in the dinucleotide
      context GA or GG is common among the lentiviruses and results in multiple stop
      codons across the genome. Hypermutated viruses have been associated with slower
      disease progression and might reflect an antiviral cell-defense mechanism.
      However, it is unclear how soon G-to-A substitutions are generated after
      infection and whether they occur randomly along the genome. In this report we
      describe for the first time hypermutated sequences detected at delivery and in
      the first weeks of life, which suggests that they could be either generated in
      utero and soon after birth and/or vertically transmitted. Hypermutated C2-C5 env
      clones were harbored in 13.2% of 243 infants and 18.6% of 199 mothers. A lower
      extent of hypermutation was found in infants than in mothers (Fisher's exact p =
      0.034), but there was no relationship between the percent hypermutated Gs and
      viral subtype or transmission status of the mother. Analyses of six hypermutated
      full-length HIV-1 clones showed that although all genes could be affected by G-to
      A substitutions, there was a significant drop in the extent of hypermutation
      between the central polypurine tract and the beginning of env, indicating that
      hypermutation across the HIV-1 genome might occur in a specific pattern. The
      genomic regions most affected by hypermutation were pol and env while both
      polypurine tracts remained unaffected. A better understanding of the mechanism of
      hypermutation may reveal novel virus-host interactions that could be targeted in
      drug development.

PMID- 14709249
TI  - A cluster of HIV type 1 subtype C sequences from Ethiopia, observed in full
      genome analysis, is not sustained in subgenomic regions.
AB  - The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. One
      approach to minimize genetic diversity in the evaluation of HIV-1 vaccines is to
      match the vaccine sequence to the predominant subtype in a vaccine cohort. Over
      two million Ethiopians are infected with HIV-1, and the predominant subtype is
      thought to be subtype C. Understanding the phylogenetic relationships between
      sequences from Ethiopia and within subtype C can help decide what sequence(s)
      should comprise a candidate vaccine. To that end, nearly full genome sequencing
      was used to characterize HIV-1 from volunteers who emigrated from Ethiopia. DNA
      extracted from peripheral blood mononuclear cells (PMBC) was amplified using
      primers in the long terminal repeats to generate nearly full-length genomes.
      Amplicons were directly sequenced with dye terminators and automated sequencers.
      Sequences were phylogenetically analyzed by neighbor joining. The six new
      Ethiopian sequences were all subtype C, consistent with previous partial and full
      genome analysis. Together with two other Ethiopian sequences, the new sequences
      formed a geographic cluster when the complete genome was analyzed. However,
      subgenomic trees showed only a weak geographic cluster, or none, with respect to
      Ethiopian strains. Although immunological responses must be considered, from a
      phylogenetic perspective, there is no compelling support for use of Ethiopian
      subtype C sequences, compared to other subtype C, as vaccine prototype strains.

PMID- 14709250
TI  - The antiviral activity of the CXCR4 antagonist AMD3100 is independent of the
      cytokine-induced CXCR4/HIV coreceptor expression level.
AB  - The chemokine receptor CXCR4 is the main coreceptor used by T-tropic X4 HIV-1
      strains to infect its target T cells. It has been proven that the CXCR4
      expression level in T cells is strongly up-regulated by interleukin (IL)-4, a Th2
      type cytokine that is secreted preferentially in HIV-infected patients in a later
      stage of disease. This results in an enhancement of HIV-1 replication in CD4+ T
      lymphocytes. We have now evaluated the potency of the CXCR4 antagonist AMD3100 in
      phytohemagglutinin (PHA)/IL-2- versus PHA/IL-4-activated T cells in order to
      determine whether the compound has comparable CXCR4-antagonistic and anti-HIV-1
      effects under these different cytokine treatments. We analyzed the CXCR4
      expression level and the dose-dependent inhibition of CXCR4 expression by
      AMD3100, by monitoring the binding of an anti-CXCR4 monoclonal antibody (clone
      12G5). We also determined stromal cell-derived factor (SDF)-1-induced
      intracellular calcium signaling and HIV-1 replication in these cells in the
      absence and presence of AMD3100. The CXCR4 expression level in PHA/IL-4
      stimulated cells was much higher than in PHA/IL-2-stimulated cells. However, the
      potency of the bicyclam AMD3100 to block anti-CXCR4 mAb binding, SDF-1-induced
      intracellular calcium signaling, and HIV-1 replication of the X4 NL4.3 strain and
      three primary isolates remained unchanged. Our data indicate that CXCR4
      antagonists such as AMD3100 act independently of the HIV-1 coreceptor expression
      level. These compounds should therefore be useful in suppressing HIV-1 infection
      in all stages of the disease.

PMID- 14709251
TI  - HIV protease inhibitor ritonavir induces lipoatrophy in male mice.
AB  - We investigated the effects of the HIV protease inhibitor ritonavir on body
      composition, serum lipids, and gene expression in C57BL/6 mice. Dual-energy X-ray
      absorptiometry measurements in ritonavir-treated male mice revealed whole-body
      lipoatrophy. In female mice fat reduction was restricted to the gonadal depot. A
      histopathological analysis showed no visible abnormalities in liver or adipose
      tissue from ritonavir-treated mice, although adipocytes were significantly
      smaller in diameter. Serum triglyceride levels were increased in ritonavir
      treated male mice. Ritonavir was coadministered with the peroxisome proliferator
      activated receptor alpha (PPARalpha) agonist gemfibrozil and the PPARgamma
      agonist rosiglitazone for 8 weeks. Neither drug alleviated the
      hypertriglyceridemia or lipoatrophy in ritonavir-treated male mice. Rather,
      gemfibrozil exacerbated the lipoatrophy. Ritonavir reduced basal expression of
      two PPARalpha target genes in liver, as well as the PPARgamma target gene
      phosphoenolpyruvate carboxykinase (PEPCK) in adipose tissues. Ritonavir partially
      inhibited induction of PPAR target genes by gemfibrozil and rosiglitazone.
      Gemfibrozil induced expression of fatty acid oxidation genes in liver, and this
      induction was less substantial when ritonavir was coadministered. Similarly,
      rosiglitazone induced expression of uncoupling protein-1, uncoupling protein-2,
      and PEPCK in adipose tissues, and this effect was partially inhibited by
      ritonavir. Thus, the effects of ritonavir on serum triglycerides and body
      composition may be due, at least in part, to an inhibition of PPAR function.

PMID- 14709252
TI  - Estimating the weight of dental amalgam restorations.
AB  - AIM: Data on the weights of amalgam restorations are lacking. The aim of this
      study was to determine these weights and to develop criteria to facilitate their
      estimation. METHODS: Four separate regression models with 4 covariates in various
      combinations were used to estimate the weight of amalgam restorations. Model I,
      based on 514 restorations from both natural and anatomical replica teeth,
      contained 3 covariates: the number of restored surfaces (covariate A), the type
      of tooth (covariate B) and whether the restoration had been removed from a
      natural tooth or an anatomical replica tooth (covariate C). Model II, based on
      359 restorations from anatomical replicas, contained 2 covariates: A and B. Model
      III, based on 155 restorations from natural teeth, contained 3 covariates:
      covariates A and B and whether the natural teeth had been extracted in 2002 or at
      least 15 years previously (covariate D). In model IV, covariate D was removed
      from model III. RESULTS: Model I explained 72% of the variation in the weight of
      restorations; the partial R2 for covariates A, B and C in model I was 0.5818,
      0.797 and 0.0579, respectively (p < 0.001). In model III, the weights of the
      restorations did not depend on covariate D (p = 0.93). The least square mean
      weight of amalgam restorations with 1, 2, 3, and 4 or more surfaces restored (and
      95% confidence interval) was 0.31 g (0.28-0.34 g), 0.49 g (0.45-0.53 g), 0.81 g
      (0.76-0.86 g) and 1.38 g (1.31-1.45 g), respectively. CONCLUSION: The number of
      surfaces restored (covariate A) accounted for at least 80% of the variation in
      the weight of restorations in all models and therefore provides the best estimate
      for the weight of amalgam restorations.

PMID- 14709253
TI  - Implant imaging for the dentist.
AB  - Dental implants have become part of routine treatment plans in many dental
      offices because of their increasing popularity and acceptance by patients.
      Appropriate preplacement planning, in which imaging plays a pivotal role, helps
      to ensure a satisfactory outcome. The development of precise presurgical imaging
      techniques and surgical templates allows the dentist to place these implants with
      relative ease and predictability. This article gives an overview of current
      practices in implant imaging for the practising dentist, with emphasis on
      selection criteria. Imaging protocols for site assessment and restorative
      evaluation are discussed. This information will enable the dentist to select and
      use appropriate radiographic images (digital or film) for implant treatment
      planning, restoration and postoperative follow-up. Modalities presented include
      intraoral and panoramic projections, linear and complex motion tomography and
      computed tomography (CT). The use of CT image reformatting software such as
      Dentascan and SimPlant with 3-dimensional reconstructions is discussed.

PMID- 14709255
TI  - The association of third molars with mandibular angle fractures: a meta-analysis.
AB  - OBJECTIVE: To estimate the relative risk of mandibular angle fractures among
      people with a lower third molar compared with those without a lower third molar.
      METHODS: Data for a case-control meta-analysis were obtained by performing a
      literature search in MEDLINE and EMBASE to identify suitable observational
      studies. To be included, studies had to present data on patients with mandibular
      fractures, incorporate cross-classified information about the presence of a lower
      third molar and indicate whether the fracture was a mandibular angle fracture on
      the ipsilateral side. RESULTS: Six studies, involving 3,002 patients with
      mandibular fractures, met the inclusion criteria. Crude relative risk estimates
      for an angle fracture, comparing patients with a third molar with those without,
      ranged from 1.2 to 12.7. There was evidence of heterogeneity across the 6 studies
      (p = 0.001), but when 2 studies with less methodologic rigour were excluded, a
      test of homogeneity was no longer statistically significant (p = 0.22). The
      estimated relative risk across the remaining 4 studies was 2.4 (95% CI 1.9 to
      3.0). CONCLUSIONS: The presence of a lower third molar may double the risk of an
      angle fracture of the mandible. This could have a bearing on any clinical
      decision on whether to extract the molar.

PMID- 14709254
TI  - Outcomes of vital primary incisor ferric sulfate pulpotomy and root canal
      therapy.
AB  - PURPOSE: To compare ferric sulfate (FS) pulpotomy and primary tooth root canal
      therapy (RCT) in cariously exposed vital pulps of primary incisors. METHODS: A
      total of 133 incisors in 50 children were randomly selected to be treated by FS
      pulpotomy (64) or RCT (69). RESULTS: Two years after treatment, 77 incisors (41
      FS pulpotomy, 36 RCT) were available for clinical and radiographic examination.
      There was no clinical evidence of pathosis in 78% of FS pulpotomy-treated and
      100% of RCT-treated incisors. Two independent pediatric dentists evaluated
      periapical radiographs of the treated incisors. Incisors were classified into 1
      of 4 treatment outcomes: N, normal treated incisor; H, nonpathologic radiographic
      change present; PO, pathologic change present, but not requiring immediate
      extraction; PX, pathologic change present, extract immediately. Survival analysis
      was applied. A moderate level of agreement between raters was found for incisors
      with outcome PX (K = 0.54). Intra-rater reliability was substantial for incisors
      with outcome PX (K = 0.61). No difference was demonstrated in the proportion of
      FS pulpotomy- and RCT-treated incisors rated PX at the 2-year recall (x2 = 0.6).
      RCT incisors demonstrated a significantly higher survival rate than FS pulpotomy
      incisors at 2 years (p = 0.04). CONCLUSIONS: Treatment outcomes for RCT incisors
      were not significantly different from FS pulpotomy-treated incisors at 2 years;
      however, at 2 years the survival rate of RCT incisors was statistically greater
      than that of FS pulpotomy-treated incisors.

PMID- 14709257
TI  - Taper proton pump inhibitor to once daily for GERD.

PMID- 14709258
TI  - Sertraline effective for children and adolescents with major depression.

PMID- 14709259
TI  - Screening and intervention for excessive drinking produce small results.

PMID- 14709260
TI  - Azithromycin ineffective for secondary coronary heart disease.

PMID- 14709261
TI  - Influenza vaccine does not prevent acute otitis media in young children.

PMID- 14709262
TI  - Elevated D-dimer level predicts recurrent VTE.

PMID- 14709263
TI  - Treating urinary incontinence in the elderly--conservative therapies that work: a
      systematic review.
AB  - OBJECTIVE: To evaluate the effectiveness of conservative treatment in the
      community-based elderly (aged > or = 55 years) with stress, urge, and mixed
      urinary incontinence. DESIGN: Systematic review of before-after studies or
      randomized controlled trials on the effect of exercise and drug therapy in
      urinary incontinence. MAIN OUTCOMES MEASURED: Reduction of urinary accidents,
      patient's perception, cystometric measurement, perineometry, and side effects.
      SEARCH STRATEGY: MEDLINE (1966-2001), EMBASE (1986-2001), Science Citation Index
      (1988-2001), The Cochrane Library, and PiCarta were searched. RESULTS Four before
      after studies and 4 randomized controlled trials were identified. Drug therapy
      alone: no study of sufficient quality. Drug therapy compared with behavioral
      therapy, 3 studies: bladder-sphincter biofeedback reduced urinary accidents in
      cases of urge or mixed incontinence by 80.7%, significantly better than
      oxybutynin (68.5%) or placebo (39.4%). Adding drug to behavioral treatment or
      behavioral to drug treatment also resulted in significant reduction in urodynamic
      urge incontinence (57.5%-88.5% vs 72.7-84.3%). Pelvic floor exercises alone
      reduced urinary accidents by 48% (compared with 53% for phenylpropanolamine) in
      patients with mixed or stress incontinence. Behavioral therapy, 5 studies:
      bladder-sphincter biofeedback in case of urge or mixed incontinence, bladder
      training in case of urge incontinence and pelvic floor exercises in case of
      stress incontinence reduced the urinary accidents with 68% to 94%. CONCLUSION:
      There are only a few studies of sufficient methodological quality on the effect
      of conservative treatment of urinary incontinence in the elderly. Behavioral
      therapy reduced urinary accidents; the effect of drug therapy is unclear. We
      recommend behavioral therapy as first choice.

PMID- 14709264
TI  - Bald spots on a young girl.

PMID- 14709265
TI  - Preventing VTE in hospitalized patients.

PMID- 14709267
TI  - Referral for small brain aneurysms.

PMID- 14709266
TI  - Why the elderly fall in residential care facilities, and suggested remedies.
AB  - OBJECTIVE: To study precipitating factors for falls among older people living in
      residential care facilities. DESIGN: Prospective cohort study. SETTING: Five
      residential care facilities. PARTICIPANTS: 140 women and 59 men, mean age +/- SD
      82.4 +/- 6.8 (range, 65-97). MEASUREMENTS: After baseline assessments, falls in
      the population were tracked for 1 year. A physician, a nurse, and a
      physiotherapist investigated each event, and reached a consensus concerning the
      most probable precipitating factors for the fall. RESULTS: Previous falls and
      treatment with antidepressants were found to be the most important predisposing
      factors for falls. Probable precipitating factors could be determined in 331
      (68.7%) of the 482 registered falls. Acute disease or symptoms of disease were
      judged to be precipitating, alone or in combination in 186 (38.6%) of all falls;
      delirium was a factor in 48 falls (10.0%), and infection, most often urinary
      tract infection, was a factor in 38 falls (7.9%). Benzodiazepines or neuroleptics
      were involved in the majority of the 37 falls (7.7%) precipitated by drugs.
      External factors, such as material defects and obstacles, precipitated 38 (7.9%)
      of the falls. Other conditions both related to the individual and the
      environment, such as misinterpretation (eg, overestimation of capacity or
      forgetfulness), misuse of a roller walker, or mistakes made by the staff were
      precipitating factors in 83 (17.2%) of falls. CONCLUSION: Among older people in
      residential care facilities, acute diseases and side effects of drugs are
      important precipitating factors for falls. Falls should therefore be regarded as
      a possible symptom of disease or a drug side effect until proven otherwise.
      Timely correction of precipitating and predisposing factors will help prevent
      further falls.

PMID- 14709268
TI  - Remembering the meanings of sensitivity, specificity, and predictive values.

PMID- 14709269
TI  - Clinical inquiries. Are inhalers with spacers better than nebulizers for children
      with asthma?

PMID- 14709270
TI  - Clinical inquiries. Do antipyretics prolong febrile illness?

PMID- 14709271
TI  - Clinical inquiries. Is folate supplementation indicated for patients with CAD?

PMID- 14709272
TI  - Clinical inquiries. Are liver function tests required for patients taking
      isoniazid for latent TB?

PMID- 14709273
TI  - Clinical inquiries. Do ACE inhibitors prevent nephropathy in type 2 diabetes
      without proteinuria?

PMID- 14709274
TI  - Clinical inquiries. What is the accuracy of stress radionuclide imaging for the
      diagnosis of CAD?

PMID- 14709275
TI  - Seeing and believing.

PMID- 14709276
TI  - Restoring accommodation to the presbyopic eye: how do we measure success?

PMID- 14709277
TI  - Misleading statistical comparison.

PMID- 14709278
TI  - Retinal nerve fiber loss after acute intraocular pressure elevation.

PMID- 14709279
TI  - Low-dose tissue plasminogen activator.

PMID- 14709280
TI  - Flap position in laser in situ keratomileusis.

PMID- 14709281
TI  - Why is the A-constant not a constant?

PMID- 14709282
TI  - Consultation section. Cataract surgical problem.

PMID- 14709283
TI  - Subluxated lens: phacoemulsification with iris hooks.
AB  - We describe a technique to manage subluxated cataracts with the use of 4 or 5
      disposable nylon iris hooks placed on the capsulorhexis edge to support the lens
      and stabilize the capsular bag during phacoemulsification. The use of an
      endocapsular tension ring provides excellent centration of the capsular bag,
      enabling endocapsular intraocular lens (IOL) implantation. Sixteen eyes with
      zonular dialysis between 90 degrees and 180 degrees had surgery with this
      technique. The mean visual acuity significantly improved from 0.26 +/- 0.18 to
      0.68 +/- 0.33 (P<.001). The surgeries were uneventful. Postoperative
      complications included cystoid macular edema 5 months after surgery in 1 eye and
      slight IOL dislocation with no symptoms detected 2 months after surgery in 4
      eyes. The technique appears to be safe, ensuring a stable IOL with reduced
      surgical risks.

PMID- 14709284
TI  - Sealed-capsule irrigation device.
AB  - We present a sealed-capsule irrigation technique and a disposable instrument that
      facilitate selective targeting of lens epithelial cells after
      phacoemulsification.

PMID- 14709285
TI  - Endoillumination-assisted cataract surgery in a patient with corneal opacity.
AB  - We present a technique to better visualize cataracts through corneal opacity. A
      70-year-old Japanese woman with retinal detachment, cataract, and corneal opacity
      in the left eye was treated with phacoemulsification, 3-port vitrectomy, and
      intraocular lens implantation. To circumvent the difficulty of performing
      continuous curvilinear capsulorhexis (CCC) and subsequent cataract surgery
      through a hazy cornea, we used an endoilluminator as a light source outside the
      cornea for CCC and inside the anterior chamber for phacoemulsification. As a
      result, CCC and subsequent cataract surgery were successfully and easily
      performed despite potentially troublesome corneal opacity. The use of an
      endoilluminator can be an effective supportive measure for cataract surgery in
      patients with corneal opacity.

PMID- 14709286
TI  - Cataract surgery without preoperative eyedrops.
AB  - We present a technique that uses intracameral lidocaine to induce pupil dilation
      without using preoperative mydriatic eyedrops. After 1 or 2 drops of topical
      lidocaine hydrochloride 1% (Xylocaine-MPF 1%) are applied to the ocular surface,
      a 1.0 mm side-port incision is created through which Xylocaine-MPF 1% is injected
      into the anterior chamber. The lidocaine paralyzes the pupil sphincter, and
      adequate mydriasis occurs within 90 seconds. Epinephrine (0.3 cc of 1:1000) is
      added to the irrigation fluid comprising balanced salt solution (BSS), and
      standard phacoemulsification with intraocular lens implantation is performed.
      Pupil dilation is maintained or increased during the procedure. Postoperatively,
      the pupil returns more quickly to normal size and reaction. Using lidocaine for
      mydriasis instead of standard dilating drops eliminates the cardiac risk of
      topical sympathetic agents, decreases the time patients wait in the holding area
      before surgery, reduces the risk of superficial punctate keratopathy, and
      provides faster recovery of normal pupil function.

PMID- 14709287
TI  - Understanding the accommodating intraocular lens.
AB  - PURPOSE: To review current accommodating intraocular lens (IOL) designs and
      introduce a new design consisting of a plus lens and a minus lens. SETTING:
      Cornea Consultants of Boston, Boston, Massachusetts, USA. METHODS: Computer
      simulation studies of a model eye calculated the pseudoaccommodation range with
      different powers of 1 IOL or of 2 IOLs acting as a doublet. RESULTS: The doublet
      consisting of a convex (plus) lens and a concave (minus) lens gave a greater
      range of power change than a single convex lens or a doublet consisting of 2
      convex lenses. The greater range of power results from the plus lens moving
      forward. CONCLUSION: The results show that an IOL design consisting of positive
      and negative lenses that move closer or farther from each other offers a greater
      range of pseudoaccommodation than other designs.

PMID- 14709288
TI  - Efficacy of brimonidine 0.2% in controlling acute postoperative intraocular
      pressure elevation after phacoemulsification.
AB  - PURPOSE: To determine the efficacy of brimonidine tartrate 0.2% drops given 2
      times a day in reducing intraocular pressure (IOP) spikes during the first 24
      hours after phacoemulsification cataract surgery. SETTING: Department of
      Ophthalmology, General Hospital of Patras Agios Andreas, Patras, Greece. METHODS:
      In this prospective double-blind placebo-controlled study, 1 eye of 40
      consecutive normotensive cataract patients having small-incision cataract surgery
      was randomized into 1 of 2 treatment arms. Twenty patients received a placebo
      (artificial tears) and 20 patients received brimonidine tartrate 0.2% drops 2
      times a day the day before and the day of surgery. Diurnal IOP variation was the
      primary efficacy variable; IOP was measured at baseline, before surgery, and 4,
      6, 12, and 24 hours postoperatively. RESULTS: The placebo group had higher IOPs
      at every time point after surgery. Peak elevation of IOP occurred 6 hours after
      surgery. The mean IOP in the placebo group (27.71 mm Hg +/- 3.75 [SD]) was
      statistically significantly higher than in the brimonidine group (21.45 +/- 1.32
      mm Hg) (P<.001). A major IOP rise (>/=20 mm Hg above baseline IOP) occurred in 1
      patient (5%) in the placebo group who required emergency hypotensive therapy.
      Twenty-four hours after surgery, 11 eyes (55%) in the brimonidine group and 4
      eyes (20%) in the placebo group had an IOP lower than baseline. CONCLUSION:
      Prophylactic treatment with brimonidine tartrate 0.2% 2 times a day for 2 days
      was effective in reducing IOP peaks throughout the first 24 hours after
      phacoemulsification surgery.

PMID- 14709289
TI  - In vivo and in vitro repeatability of Hartmann-Shack aberrometry.
AB  - PURPOSE: To assess the in vivo and in vitro repeatability of objective refraction
      and higher-order aberrations (HOAs) measured by a commercially available Hartmann
      Shack wavefront sensor. SETTING: Department of Ophthalmology, Johann-Wolfgang
      Goethe University, Frankfurt am Main, Germany. METHODS: After pupil dilation of
      40 myopic or myopic, astigmatic eyes of 20 patients, wavefront measurements were
      performed 6 times in each eye and in a test object provided by the manufacturer
      by 2 experienced examiners using a Hartmann-Shack wavefront sensor (Zywave,
      software version 3.21, Bausch & Lomb). The mean standard deviation (SD) and the
      coefficient of variation (CV) for sphere, cylinder, and each Zernike polynomial
      were computed for a 7.0 mm pupil diameter. Vector analysis was performed for the
      astigmatism. After the data were subdivided into 2 groups with 3 measurements in
      each, one measurement that best matched the subjective manifest refraction was
      chosen in each group and the difference between them was calculated. RESULTS: The
      mean SD (CV) was 0.15 diopter (D) (7%) for the sphere value of the predicted
      phoropter refraction and 0.16 D (22%) for astigmatism. Thirty-two eyes had an
      axis deviation of at least 10 degrees. Vector analysis revealed a mean SD of
      0.24@109.8. Other results for mean SD and mean CV were as follows: total in vivo
      higher-order RMS, 0.097 microm, 13.4%; sphere in myopic test device, 0.034 D,
      0.65%; sphere in hyperopic test object, 0.035 D, 0.72%. The difference between
      the 2 best-matched refractions was significantly different from zero (0.11 D,
      P<.001). The CV was significantly higher for HOAs than for the 2nd-order
      aberrations (defocus and astigmatism). CONCLUSIONS: Repeatability of Hartmann
      Shack aberrometry by the Zywave wavefront sensor was not satisfactory,
      particularly for small amounts of HOAs. Under these conditions, aberrometry
      measurements should be repeated several times and outliers should be excluded in
      calculating the means.

PMID- 14709290
TI  - Effect of laser in situ keratomileusis on optic nerve head topography and retinal
      nerve fiber layer thickness.
AB  - PURPOSE: To determine whether laser in situ keratomileusis (LASIK) produces
      significant changes in optic nerve head (ONH) topography and retinal nerve fiber
      layer (RNFL) thickness as measured by the Heidelberg Retina Tomograph (HRT) and
      to evaluate the potential neuroprotective effect of topical betaxolol on these
      changes. SETTING: Department of Ophthalmology, University of Texas Southwestern
      Medical Center, Dallas, Texas, USA. METHODS: In this prospective randomized
      double-masked comparative case series, 34 patients having LASIK for myopia were
      randomly assigned to receive topical betaxolol 0.5% solution or placebo twice a
      day for 2 days before the procedure and 7 days after the procedure. Preoperative
      and postoperative (1 week and 1 and 3 months) images were made with the HRT. Four
      HRT parameters (rim area, rim volume, mean RNFL thickness, and cup shape measure)
      were analyzed in a masked fashion. The Student paired t test was used for
      statistical analysis. RESULTS: No significant changes from baseline occurred in
      any HRT parameter in either patient group or when the patients were evaluated as
      a single group. CONCLUSIONS: Laser in situ keratomileusis did not adversely
      affect ONH morphology or RNFL thickness as measured by HRT. Since no neural
      damage was detected, the potential neuroprotective effect of betaxolol could not
      be evaluated.

PMID- 14709291
TI  - To lift or recut: changing trends in LASIK enhancement.
AB  - PURPOSE: To report serious complications caused by recutting laser in situ
      keratomileusis (LASIK) flaps for enhancement and reconsider the current preferred
      method of LASIK enhancement. SETTING: Multiple surgeon practices. METHODS: This
      retrospective noncomparative nonconsecutive case series comprised LASIK patients
      in the private practices of 9 experienced refractive surgeons and those reported
      in a survey of refractive surgeons. Case histories, refractions, corneal
      topographies, slitlamp photographs, and measurements of uncorrected and best
      corrected (BCVA) visual acuity after recutting LASIK flaps were collected.
      Surveys of refractive surgeons and an analysis of changing practice trends among
      the authors and these surgeons were assessed. RESULTS: In 12 cases, significant
      loss of BCVA and subjective visual difficulties resulted from recutting LASIK
      flaps. Most surveyed surgeons had changed their practice from recutting to
      lifting flaps even 9 to 10 years postoperatively with good results. CONCLUSION:
      Recutting flaps for enhancement should be avoided unless other alternatives are
      unavailable.

PMID- 14709292
TI  - Understanding, retaining, and removing dispersive and pseudodispersive ophthalmic
      viscosurgical devices.
AB  - PURPOSE: To analyze and explain the rheologic behavior of pseudodispersive
      viscoadaptive ophthalmic viscosurgical devices (OVDs) and compare it with that of
      dispersive OVDs. SETTING: York Finch Eye Associates and Humber River Regional
      Hospital, Toronto, Ontario, Canada. METHODS: Poiseuille's law was used as a basis
      of understanding fluid aspiration. Each OVD class was analyzed to determine how
      well it fit the law and why. RESULTS: Higher viscosity cohesive OVDs are removed
      in a manner predicted by Poiseuille's law. Lower viscosity dispersive and
      viscoadaptive OVDs are not. CONCLUSIONS: Lower viscosity dispersive OVDs possess
      inadequate cohesion to maintain continuous contact with the aspiration port
      during irrigation/aspiration, whereas viscoadaptive OVDs are too rigid to permit
      scrolling around obstacles in the eye (the intraocular lens), also resulting in
      interrupted contact with the aspiration port. Dispersion and pseudodispersion
      represent opposite ends of a spectrum of increasing cohesion and rigidity
      correlating with increasing zero-shear viscosity and are not similar.

PMID- 14709293
TI  - Stability of refraction, accommodation, and lens position after implantation of
      the 1CU accommodating posterior chamber intraocular lens.
AB  - PURPOSE: To investigate stability of refraction, anterior chamber depth (ACD),
      and accommodation up to 12 months after implantation of the 1CU accommodating
      posterior chamber intraocular lens (PC IOL). SETTING: Department of
      Ophthalmology, University Erlangen-Nurnberg, Erlangen, Germany. METHODS: In a
      prospective study, 15 eyes of 15 patients (mean age 62.2 years +/- 13.4 [SD]
      [range 44 to 86 years]) had phacoemulsification and PC IOL implantation. Distance
      refraction, accommodative range measured by the near point with an
      accommodometer, ACD measured with the IOLMaster (Carl Zeiss Meditec), and near
      visual acuity with best distance correction (Birkhauser charts at 35 cm) were
      determined after 3, 6, and 12 months and analyzed for signs of systematic
      changes. RESULTS: After 3, 6, and 12 months, the mean distance refraction was 
      0.28 +/- 0.54 diopters (D), -0.29 +/- 0.52 D, and -0.21 +/- 0.54 D, respectively;
      the mean accommodative range, 1.93 +/- 0.47 D, 1.85 +/- 0.62 D, and 2.02 +/- 0.38
      D, respectively; the mean ACD without pharmacological induction of ciliary muscle
      contraction, 4.40 +/- 0.44 mm, 4.35 +/- 0.50 mm, 4.25 +/- 0.53 mm, respectively;
      and the mean near visual acuity with best distance correction, 0.41 +/- 0.15,
      0.37 +/- 0.12, and 0.39 +/- 0.11, respectively. There were no statistically
      significant changes in any measurement during the follow-up (P>.1). CONCLUSIONS:
      Refraction, ACD, and accommodative range remained stable without indication of a
      systemic trend toward myopia, hyperopia, PC IOL dislocation, or regression of
      accommodative properties. The 1CU accommodating PC IOL provided stable
      refraction, accommodation, and PC IOL position for up to 1 year.

PMID- 14709294
TI  - Lack of fluorophotometric evidence of aqueous-vitreous barrier disruption after
      posterior capsulorhexis.
AB  - PURPOSE: To evaluate the integrity of the aqueous-vitreous barrier by assessing
      the flow of fluorescein from the anterior chamber to the anterior vitreous using
      fluorophotometry in eyes with a posterior continuous curvilinear capsulorhexis
      (PCCC) and in eyes without a PCCC. SETTING: University Hospital Antwerp, Edegem,
      Belgium. METHODS: Ten patients had bilateral extracapsular cataract extraction
      with implantation of an intraocular lens. In 1 eye, a PCCC was performed; the
      other eye served as a negative control. The eyes of 2 other patients who had
      complicated cataract surgery with posterior capsule and anterior hyaloid membrane
      rupture served as positive controls. All patients had fluorophotometry of both
      eyes 12 to 18 months after surgery to measure the flow of fluorescein from the
      anterior chamber to the anterior vitreous. RESULTS: There were no statistically
      significant differences in the distribution pattern of fluorescein between eyes
      with PCCC and eyes without PCCC. In contrast, enhanced flow was detected in both
      eyes with rupture of the posterior capsule and the anterior hyaloid. CONCLUSIONS:
      In this fluorophotometry study, a PCCC did not seem to disrupt the aqueous
      vitreous barrier. Results indicate that an intact anterior vitreous membrane is
      crucial to maintain the barrier function between the anterior and the posterior
      segments of the eye.

PMID- 14709295
TI  - Two-year results of conductive keratoplasty for the correction of low to moderate
      hyperopia.
AB  - PURPOSE: To evaluate the 2-year postoperative safety, efficacy, predictability,
      and stability results of conductive keratoplasty (CK) to correct low to moderate
      hyperopia. SETTING: Department of Ophthalmology, Stanford University Medical
      Center, Stanford, California, USA. METHODS: In a prospective nonrandomized
      noncontrolled trial, 25 eyes of 14 patients with +0.75 to +3.00 diopters (D) of
      hyperopia and </=0.75 D of cylinder were treated with CK. Low-energy, radio
      frequency current was applied to the peripheral corneal stroma through a probe
      inserted at 8 to 32 treatment spots. An early nomogram was used in 2 eyes, and a
      current nomogram was used in 23 eyes; the intended refraction was plano. The 23
      eyes treated with the current nomogram were analyzed for efficacy,
      predictability, and stability. All 25 eyes were included in the safety and
      patient-satisfaction analyses. RESULTS: Preoperatively, the mean manifest
      refraction spherical equivalent (MRSE) in the 23 current-nomogram eyes was +1.55
      D. At 2 years, the uncorrected visual acuity was 20/20 or better in 64% of eyes
      and 20/40 or better in 95%. The MRSE was within +/-0.50 D in 64% of eyes, within
      +/-1.00 D in 91%, and within +/-2.00 D in 100%. No eye lost more than 1 line of
      best spectacle-corrected visual acuity or had an induced cylinder greater than
      0.75 D. The mean MRSE of the cohort with all follow-ups was +0.48 D, which
      reflected a 29% regression from the intended plano and 43% regression from the 1
      month postoperative overcorrection. The rate of regression appeared to be low and
      decreasing, +0.024 D per month between 12 and 24 months. A patient survey
      revealed improved quality of vision and a high level of satisfaction.
      CONCLUSIONS: Conductive keratoplasty appeared to be safe, effective, and
      predictable for correcting low to moderate hyperopia. Mild hyperopic regression
      was observed; however, the rate of regression indicated by the mean change in
      MRSE per month was low and decreased over the 2-year follow-up. Longer follow-up
      may be necessary to further characterize the refractive stability of CK.

PMID- 14709296
TI  - Comparison of LADARVision and Visx Star S3 laser in situ keratomileusis outcomes
      in myopia and hyperopia.
AB  - PURPOSE: To compare visual outcomes with 2 commonly used excimer lasers, the
      Autonomous LADARVision (LV) (Alcon Laboratories Inc.) and the Visx Star S3 (S3),
      in the performance of myopic and hyperopic astigmatic laser in situ
      keratomileusis (LASIK). SETTING: Zale Lipshy University Hospital Laser Center for
      Vision, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
      METHODS: In this retrospective single-center 3-surgeon cohort comparison, 100
      consecutive LV-treated myopic eyes with a mean manifest refraction spherical
      equivalent (MRSE) of -3.22 diopters (D) (range 0 to -6.00 D) (mean astigmatism
      0.95 D [range 0 to 4.00 D]) were compared with 100 consecutive S3-treated eyes
      with a similar MRSE (mean MRSE -3.19 D; mean astigmatism 0.66 D [range 0 to 2.75
      D]). Forty-one consecutive LV-treated hyperopic eyes with a mean MRSE of +2.59 D
      (range +1.00 to +6.00 D) (mean astigmatism 0.89 D [range 0 to 3.50 D]) were
      compared with 25 consecutive S3-treated eyes with a similar MRSE (mean MRSE +2.70
      D; mean astigmatism 0.87 D [range 0 to 2.75 D]). The following outcomes were
      compared: uncorrected visual acuity, refractive predictability and stability,
      gain or loss of best spectacle-corrected visual acuity, and need for enhancement.
      RESULTS: Statistically significant differences in outcomes were found between
      lasers in the treatment of hyperopia and hyperopic astigmatism. No outcome
      differences between lasers were found in the treatment of myopia and myopic
      astigmatism. CONCLUSION: The LV and S3 lasers yielded equivalent results in
      myopic LASIK between 0 and -6.00 D; however, the LADARVision yielded
      statistically significantly better results in hyperopic LASIK between +1.00 and
      +6.00 D.

PMID- 14709297
TI  - Characteristic clinical findings and visual outcomes.
AB  - PURPOSE: To describe a potentially serious complication of laser in situ
      keratomileusis (LASIK) that can masquerade as a persistent epithelial defect.
      SETTING: Refractive surgery centers in academic institutions. METHODS: Charts of
      4 eyes in which epithelial-defect-masquerade syndrome was diagnosed were reviewed
      to determine the time to diagnosis and the presence of associated features that
      may have contributed to the delay in diagnosis. Clinical findings and outcomes of
      medical and surgical intervention were recorded. RESULTS: All eyes developed an
      epithelial defect involving the edge of the flap during surgery. The diagnosis of
      epithelial ingrowth was delayed because of the presence of stromal edema (n = 4),
      diffuse lamellar keratitis (n = 3), and contraction of the flap leading to gutter
      widening (n = 4). Epithelial ingrowth was diagnosed 5, 7, 15, and 60 days after
      LASIK. All eyes satisfied the following criteria: convexity of the peripheral
      epithelium at the edge of the flap associated with light reflections at the end
      of the flap, fluorescein pooling in the gutter, stromal edema, reduced best
      spectacle-corrected visual acuity (<20/60 in 3 eyes), and partial healing of the
      epithelial defect limited to the flap hinge. One eye developed stromal scarring
      and ulceration that required fortified antibiotics. Surgical repair included
      epithelial scraping after the flap was lifted and ironing followed by placement
      of a contact lens after surgery. The epithelial defect healed 5, 7, 21, and 24
      days after surgery. The final uncorrected visual acuity ranged from 20/15 to
      20/100. CONCLUSIONS: Epithelial ingrowth following LASIK-associated epithelial
      defects may masquerade as stromal edema associated with a persistent epithelial
      defect. A high index of suspicion for epithelial ingrowth is essential to avoid a
      delayed diagnosis, which can result in irreversible visual loss due to stromal
      melting and infectious keratitis.

PMID- 14709298
TI  - Intracameral mydriatics in phacoemulsification cataract surgery.
AB  - PURPOSE: To evaluate intracameral injection of mydriatics in phacoemulsification
      cataract surgery and compare the results with those of conventional topical
      mydriatics. SETTING: Department of Clinical Science/Ophthalmology, Umea
      University Hospital, Umea, Sweden. METHODS: This prospective randomized double
      blind study included 60 patients who were given topical (topical group) or
      intracameral (intracameral group) mydriatics. The topical mydriatics comprised 3
      drops of cyclopentolate 1% and phenylephrine 10% given 15 minutes apart and 150
      microL intracameral lidocaine hydrochloride 1% (Xylocaine) and the intracameral
      mydriatics, placebo eyedrops and 150 microL intracameral cyclopentolate 0.1%,
      phenylephrine 1.5%, and Xylocaine 1%. The pupil size was recorded preoperatively,
      throughout surgery, and 1 day and 1 month postoperatively. Preoperative and
      postoperative corneal endothelial morphology, corneal thickness, intraocular
      pressure, visual acuity, aqueous cells and flare, phacoemulsification energy,
      duration of surgery, pulse, blood pressure, and intraoperative sensation of pain
      and glare were also recorded. RESULTS: With intracameral mydriatics, mydriasis
      reached 95% +/- 3% (SD) of its final value within 20 seconds. In the intracameral
      group, the pupils were smaller than in the topical group (mean 6.7 +/- 1.0 mm
      versus 7.7 +/- 1.0 mm, P<.001) but did not contract intraoperatively. The pupils
      in the topical group tended to contract, and the difference between groups was
      significant (P =.0020). The intracameral group reported less glare during the
      procedure (P<.001). There was no difference in endothelial cell loss,
      inflammatory reaction, postoperative corneal swelling, or surgical performance
      between the groups. CONCLUSIONS: Intracameral mydriatics were a rapid, effective,
      and safe alternative to topical mydriatics in phacoemulsification. Their use can
      simplify preoperative routines and in certain high-risk groups, may reduce the
      risk for cardiovascular side effects.

PMID- 14709299
TI  - Prednisolone and flurbiprofen drops to maintain mydriasis during
      phacoemulsification cataract surgery.
AB  - PURPOSE: To compare the effects on the pupil of pretreatment with prednisolone 1%
      eyedrops, flurbiprofen 0.03% eyedrops, and sodium chloride 0.9% eyedrops in
      patients having phacoemulsification cataract surgery. SETTING: Christopher Home
      Eye Unit, Royal Albert Edward Infirmary, Wigan, United Kingdom. METHODS: One
      hundred thirty-six white patients having phacoemulsification with no history of
      eye disease, antiinflammatory medication, or diabetes were enrolled in this
      prospective randomized double-blind study. Patients were allocated to receive
      flurbiprofen 0.03%, prednisolone 1%, or sodium chloride 0.9% (placebo) eyedrops
      at 30-minute intervals beginning 2 hours before surgery. All patients received
      cyclopentolate 1% and phenylephrine 2.5% drops preoperatively and epinephrine
      1:10(6) intraoperatively in the intraocular irrigating solution. The pupil
      diameter was measured from a television screen at the preset magnification of the
      operating microscope immediately before the incision, at the end of nucleus
      emulsification, at the end of irrigation/aspiration (I/A), and at the end of
      surgery. One hundred twelve patients with a baseline pupil diameter of at least
      6.0 mm who had uneventful phacoemulsification were analyzed. RESULTS: The
      baseline pupil diameters were statistically similar. An analysis of variance did
      not reveal an overall significant mydriasis-maintaining effect of prednisolone or
      flurbiprofen compared to the placebo at any stage of surgery (P =.16 to.37). The
      95% confidence interval showed flurbiprofen to be superior to prednisolone at the
      end of surgery. According to the paired t test, the reduction from the baseline
      at the end of I/A in the prednisolone group (P =.051) and at the end of surgery
      in the flurbiprofen group (P =.22) was not significant. CONCLUSION: In the
      presence of epinephrine in the intraocular irrigating solution, both prednisolone
      1% and flurbiprofen 0.03% failed to maintain mydriasis at the crucial steps of
      nuclear emulsification and cortical I/A.

PMID- 14709300
TI  - Treatment of acute pseudophakic cystoid macular edema: Diclofenac versus
      ketorolac.
AB  - PURPOSE: To investigate whether topical diclofenac sodium 0.1% solution (Voltaren
      Ophthalmic) is as efficacious as topical ketorolac tromethamine 0.5% solution
      (Acular) in the treatment of established, chronic cystoid macular edema (CME)
      after uneventful phacoemulsification cataract extraction with posterior chamber
      intraocular lens (IOL) implantation. SETTING: Referral-based vitreoretinal
      private practice. METHODS: This randomized prospective study comprised 34
      consecutive patients with clinical CME after uneventful phacoemulsification
      cataract extraction with posterior chamber IOL implantation who were referred to
      a private vitreoretinal practice for evaluation and management. Exclusion
      criteria included a history of previous intraocular surgery, vitreous loss during
      cataract surgery, CME, uveitis, and vitreoretinal pathology. The eye with CME was
      treated with 1 drop 4 times daily of diclofenac sodium 0.1% solution or ketorolac
      tromethamine 0.5% solution. Outcomes were measured by observing for improvement
      in CME and visual acuity. RESULTS: Both treatment methods resulted in a
      significant reduction in CME and a significant improvement in visual acuity.
      Within 26 weeks, diclofenac reduced CME in 16 patients (89%) and ketorolac, in 14
      patients (88%) (P =.92, confidence interval [CI] 95%). Within 26 weeks,
      diclofenac eliminated CME in 14 patients (78%) and ketorolac, in 12 patients
      (75%) (P =.86, CI 95%). The mean time to initial CME reduction was 7.5 weeks with
      diclofenac and 8.0 weeks with ketorolac (P =.41, CI 95%). The mean time to CME
      resolution was 13.6 weeks with diclofenac and 12.8 weeks with ketorolac (P =.49,
      CI 95%). CONCLUSIONS: Diclofenac sodium 0.1% solution and ketorolac tromethamine
      0.5% topical ophthalmic solution eyedrops were equally effective in reducing the
      severity and duration of CME after uneventful phacoemulsification with posterior
      chamber IOL implantation. Either solution may be considered for CME after
      cataract surgery, especially in patients who may not tolerate corticosteroid
      treatment.

PMID- 14709301
TI  - Neodymium:YAG laser capsulotomy in vitrectomized pseudophakic eyes with
      persistent endotamponade.
AB  - PURPOSE: To evaluate the feasibility and limits of neodymium:YAG (Nd:YAG) laser
      capsulotomy in eyes with persistent endotamponade. SETTING: Department of
      Ophthalmology, University Cologne, Cologne, Germany. METHODS: In this consecutive
      series, an Nd:YAG laser capsulotomy was performed by 1 surgeon in 6 eyes with
      posterior capsule opacification (PCO) and persistent endotamponade caused by
      proliferative vitreoretinopathy. The endotamponade was with silicone oil (5000
      centistokes) in 5 eyes and with perfluorohexyloctane (F(6)H(8)) in 1 eye. Also
      evaluated were 6 vitrectomized eyes without endotamponade that had an Nd:YAG
      laser capsulotomy for PCO by the same surgeon. All 12 eyes were pseudophakic. The
      mean follow-up after capsulotomy was approximately 6 months (range 2 to 12
      months). Follow-up examinations included visual acuity, intraocular pressure
      measurement, and IOL centration and capsule reopacification evaluation. RESULTS:
      The total energy required was higher in eyes with persistent endotamponade. In 3
      of these eyes, the laser capsulotomy could not be successfully completed and was
      surgically enhanced. The laser capsulotomy in eyes without endotamponade was
      successful in all cases. Complete reopacification occurred in 2 eyes with
      persistent endotamponade within 2 months and in no eye without endotamponade.
      Improvement in visual acuity was limited in all eyes because of retinal
      pathology. CONCLUSIONS: Neodymium:YAG laser capsulotomy in pseudophakic eyes with
      persistent endotamponade was successful but had a relatively high reintervention
      rate. The visual prognosis was limited in all cases because of retinal pathology.

PMID- 14709302
TI  - Transscleral fixation of a foldable intraocular lens in aphakic vitrectomized
      eyes.
AB  - PURPOSE: To evaluate the clinical outcomes of transscleral fixation of a foldable
      intraocular lens (IOL) in eyes that had pars plana lensectomy combined with pars
      plana vitrectomy for severe vitreoretinal disease. SETTING: Seoul National
      University Hospital, Seoul, Korea. METHODS: The medical records of 21 patients
      who had a transscleral fixation of a foldable IOL after previous vitrectomy
      combined with lensectomy for severe posterior segment pathology were reviewed.
      The underlying vitreoretinal diseases were complicated proliferative diabetic
      retinopathy (n = 9), proliferative vitreoretinopathy (n = 5), traumatic retinal
      detachment (n = 3), intraocular foreign body (n = 2), and uveitic retinal
      detachment (n = 2). The postoperative best corrected visual acuity (BCVA) was
      compared with the preoperative BCVA. Autorefractometry and keratometry
      measurements and central endothelial cell counts were evaluated 1 day
      preoperatively and 6 months postoperatively. RESULTS: The mean age of the
      patients was 54.5 years. The preoperative aphakic period ranged from 2 to 22
      months. The visual acuity reached the preoperative BCVA by 2 months after surgery
      and was better than the preoperative BCVA at 6 months (P =.006) and at the final
      visit (P =.003). Six months postoperatively, the mean myopic shift by cycloplegic
      autorefractometry was -1.0 diopter (D) and the mean scalar shift in surgically
      induced keratometric cylinder, 1.0 D. The mean central corneal endothelial loss
      at 6 months was 6.7% (range 2.4% to 22.2%). The only vitreoretinal complications
      were a transient vitreous hemorrhage and a reopened macular hole that was
      reattached after fluid-gas exchange. CONCLUSION: Transscleral fixation of a
      foldable IOL was safe and led to favorable visual outcomes in aphakic
      vitrectomized eyes with previous severe vitreoretinal disease.

PMID- 14709303
TI  - Refractive outcomes after arcuate keratotomy using the Terry astigmatome.
AB  - PURPOSE: To investigate the refractive outcomes after arcuate keratotomy for
      astigmatism. SETTING: Uludag University, Faculty of Medicine, Department of
      Ophthalmology, Bursa, Turkey. METHOD: Sixteen eyes of 11 patients with
      astigmatism had arcuate keratotomy using the Terry astigmatome. The mean age of
      the patients was 36 years +/- 10 (SD). All patients received preoperative and
      postoperative ophthalmic examinations consisting of best spectacle-corrected
      (BSCVA) and uncorrected (UCVA) visual acuities, corneal topography, and
      ultrasonic pachymetry. Surgery was performed using topical anesthesia of
      oxybuprocaine 0.1% eyedrops. The Terry astigmatome was selected by the mean
      paracentral (estimated incision area) corneal thickness. All patients received
      topical ofloxacin 0.3% and topical diclofenac 0.1% eyedrops postoperatively.
      RESULTS: The mean corneal astigmatism was -4.0 +/- 1.1 diopters (D) (range -2.2
      to -6.0 D) preoperatively and -1.8 +/- 0.8 D (range -0.6 to -3.0 D)
      postoperatively. The mean surgically induced corneal astigmatism was 2.5 +/- 0.6
      D. The mean UCVA (logMAR) was 0.74 +/- 0.25 preoperatively and 0.18 +/- 0.23 1
      week postoperatively, and the mean BSCVA (logMAR) was 0.19 +/- 0.24 and 0.19 +/-
      0.23, respectively. There were no intraoperative or postoperative complications.
      CONCLUSION: Arcuate keratotomy using the Terry astigmatome was a safe and
      reliable treatment for corneal astigmatism.

PMID- 14709304
TI  - Effect of central corneal thickness on surgically induced astigmatism in cataract
      surgery.
AB  - PURPOSE: To evaluate the effect of central corneal thickness (CCT) on surgically
      induced astigmatism (SIA) in cataract surgery using temporal clear corneal
      incisions. SETTING: Department of Ophthalmology, Seoul National University
      Hospital, Seoul, Korea. METHODS: The retrospective nonrandomized clinical study
      comprised 129 eyes that had cataract surgery performed through a sutureless
      temporal clear corneal incision. Eyes were categorized according to the axis of
      the preoperative astigmatism: against the rule (ATR, 0 to 45 degrees; n = 64) or
      with the rule (WTR, 46 to 90 degrees; n =65). Corneal topography was taken
      preoperatively and 1 day and 2 months postoperatively to evaluate the change in
      the cornea. The SIA was calculated using the polar method from simulated
      keratometric readings obtained with topography. Correlations between SIA and CCT
      were analyzed by linear regression analysis and compared between the ATR and the
      WTR groups. RESULTS: One day postoperatively, the SIA was negatively correlated
      with CCT in the ATR group but not in the WTR group (P =.050 versus P =.92; linear
      regression analysis). At 2 months, the correlation between CCT and SIA was no
      longer statistically significant. CONCLUSIONS: Central corneal thickness was
      negatively correlated with the amount of SIA immediately postoperatively when the
      preoperative astigmatism was ATR. The correlation was not present 2 months after
      surgery. These results may be applied to abnormally thin corneas such as those
      after keratorefractive surgery.

PMID- 14709305
TI  - Traumatic subconjunctival crystalline lens dislocation.
AB  - PURPOSE: To evaluate the clinical features and visual outcomes in patients with
      traumatic subconjunctival crystalline lens dislocation. SETTING: Izmir Ataturk
      Education and Research Hospital, Department of Ophthalmology, Izmir, Turkey.
      METHODS: The clinical records of 5 patients with subconjunctival crystalline lens
      dislocation secondary to blunt trauma were reviewed. RESULTS: The median age of 3
      women and 2 men was 63 years (range 62 to 73 years). The lenses were dislocated
      to the superior (n = 1), temporal (n = 1), superotemporal (n = 1), and
      superonasal (n = 2) quadrants. All patients had various degrees of hyphema and
      vitreous hemorrhage. One patient had traumatic optic neuropathy. Visual acuity
      improved in all patients after lens removal and scleral rupture repair.
      CONCLUSION: With timely intervention, the visual outcome was reasonably good in
      patients with subconjunctival dislocation of the crystalline lens.

PMID- 14709306
TI  - Effect of ophthalmic viscosurgical devices on lens epithelial cells: a
      morphological study.
AB  - PURPOSE: To investigate the morphological effects of Viscoat (sodium hyaluronate
      3.0%-chondroitin sulfate 4.0%) on lens epithelial cells (LECs). SETTING:
      Department of Ophthalmology, University of Texas Southwestern Medical Center,
      Dallas, Texas, USA, and the Laboratory of Ultrastructural Morphology, Zoological
      Institute, University of Liege, Liege, Belgium. METHODS: Human LECs collected via
      capsulorhexis were examined by light microscopy (LM) and transmission electron
      microscopy (TEM). Lens epithelial cells from rabbit capsulorhexis samples were
      studied by LM and TEM following exposure to Provisc (sodium hyaluronate 1.0%) or
      Viscoat ophthalmic viscoelastic device (OVD). Since Viscoat is hypertonic (340
      mOsm), hypertonic, isotonic, and hypotonic solutions were compared to investigate
      a possible mechanism for the observed effects. The effects of Provisc and Viscoat
      on rabbit LECs in the intact lens were also compared. RESULTS: Human LECs
      gathered via capsulorhexis following exposure to Viscoat were generally thinner
      than control samples and often had condensed nuclei and increased intracellular
      vacuolization. Rabbit capsular tissue exposed in situ to Viscoat demonstrated
      changes similar to those seen in humans. Cells exposed to Provisc were similar to
      cells in untreated controls in humans and rabbits. Corneal endothelial cells
      exposed to either agent were unaffected. Experiments with hypertonic and
      hypotonic buffers induced some of the changes noted with Viscoat, but the effects
      were less severe. Lens epithelial cells in intact rabbit lenses exposed to
      Viscoat appeared similar to LECs in the control samples. CONCLUSIONS: Light
      microscopy and TEM of human lens capsule tissue suggest that Viscoat induces
      significant morphological changes in LECs during cataract surgery. The changes
      may underlie the improved visualization of these cells that has been reported
      during cataract surgery. Corneal endothelial cells were unaffected by exposure to
      Viscoat. Studies in a rabbit model suggest that the hyperosmolarity of Viscoat
      may play a partial role in the LEC changes.

PMID- 14709307
TI  - Ectasia after laser in situ keratomileusis.
AB  - Eighty-five cases of post laser in situ keratomileusis ectasia were reviewed and
      analyzed. Cases of keratoconus or forme fruste keratoconus were eliminated; many
      remaining case reports lacked key information. The current literature is unable
      to define a specific residual corneal thickness or a range of preoperative
      corneal thickness that would put an eye at risk for developing ectasia. The most
      logical cause for eyes without preexisting pathology to develop ectasia is a
      postablation stromal thickness that is mechanically unstable; this "minimal"
      thickness is probably specific to each eye. The preoperative and postoperative
      corneal thickness, measured flap thickness, and microkeratome and laser
      parameters used in a given case are required to determine the range of residual
      corneal thickness that puts the eye at risk for developing ectasia. Other as yet
      undetermined factors may play a role in the development of this complication.

PMID- 14709308
TI  - Refractive lensectomy and accommodating lens implantation in a case of hyperopia.
AB  - We present a 39-year-old woman with high hyperopia who developed an intolerance
      to contact lenses due to dry-eye syndrome and Grave's disease. Refractive
      lensectomy with implantation of a custom-made +31.00 diopter (D) accommodating
      intraocular lens (IOL) (1CU, HumanOptics) was performed in both eyes. This
      foldable IOL has modified haptics with transmission elements that allow axial
      movement of the IOL optic and capsular bag secondary to contraction of the
      ciliary muscle. The calculated pseudophakic accommodation induced by the anterior
      shift of a +31.00 D IOL is 2.20 D per millimeter of axial displacement. After 6
      months, the accommodative range determined by defocusing was 3.00 D. The
      subjective near point with best distance correction was 32.00 cm. Refractive
      lensectomy and implantation of an accommodating IOL based on focus shift may be a
      refractive solution in eyes with high hyperopia and a short axial length.

PMID- 14709309
TI  - Imaging scleral expansion bands for presbyopia with optical coherence tomography.
AB  - A 57-year-old woman was treated for mild presbyopia with implantation of scleral
      expansion bands (SEB). Although near vision was temporarily restored, the effect
      dissipated after 1 year. Slitlamp-adapted optical coherence tomography (OCT) at
      1310 nm allowed precise cross-sectional visualization of the hyporeflective
      intrascleral segments. The OCT method provided precise images of the segment
      depth and thickness, the scleral thickness at the scleral spur, the anterior
      chamber angle, and the angle-opening distance. Intrascleral tilting of 1 segment
      was seen; this required removal of the SEB because of marked foreign-body
      sensation. Noncontact, slitlamp-adapted OCT can be used to evaluate scleral
      changes after SEB implantation.

PMID- 14709310
TI  - Collamer intraocular lens implantation with active uveitis.
AB  - Two patients with active iritis developed cataracts and had successful cataract
      surgery with implantation of a Collamer (Staar Surgical, AG) intraocular lens
      (IOL). Both patients developed severe bilateral uveitis, which in 1 patient was
      refractory to control. Different IOL materials have been used in iritis patients
      with varying degrees of success. The IOLs used in these patients remained free of
      cellular and noncellular deposits, such as those that frequently develop on the
      anterior surface of IOLs in uveitis patients. Two of the 3 eyes developed a
      secondary membrane that was successfully treated by a neodymium:YAG laser
      posterior capsulotomy.

PMID- 14709311
TI  - Implantation of a custom intraocular lens with a 30-diopter torus for the
      correction of high astigmatism after penetrating keratoplasty.
AB  - We present a 62-year-old woman who had implantation of an intraocular lens (IOL)
      with a torus of 30.0 diopters (D) in an eye after penetrating keratoplasty. The
      patient presented with cataract and a best corrected visual acuity of 20/400.
      Penetrating keratoplasty was performed in 1975 because of decompensated
      keratoconus. With a clear but inferiorly decentered corneal graft, visual acuity
      was limited because of keratoplasty-related high corneal astigmatism of 22.5@156
      that could not be successfully treated with spectacles or contact lenses. A
      custom toric IOL with -30.0 D of cylindrical power was implanted in the capsular
      bag via a sclerocorneal tunnel incision. Additionally, a spherical IOL of -15.0 D
      sphere was implanted in the ciliary sulcus. Six months after implantation, the
      IOLs were still well centered and the uncorrected visual acuity was 20/60.

PMID- 14709312
TI  - Effect of flap hinge placement on post-laser in situ keratomileusis wound healing
      in the presence of superior corneal vascularization.
AB  - We report a case that demonstrates a difference in wound healing after laser in
      situ keratomileusis using microkeratomes with both superior and nasal hinges in a
      patient with bilateral superior corneal vascularization. Subsequently, the
      patient experienced lamellar keratitis, epithelial defects, and peripheral
      thinning in both eyes. These postoperative conditions were more extensive and
      required more time to resolve in the eye with a nasal hinge flap. Creating a
      superiorly hinged flap decreases the likelihood of transecting extensive corneal
      pannus and may reduce the degree of postoperative complications.

PMID- 14709313
TI  - Corneal perforation after conductive keratoplasty with previous refractive
      surgery.
AB  - A 56-year-old woman had conductive keratoplasty (CK) for residual hyperopia and
      astigmatism. Three years before the procedure, the patient had arcuate
      keratotomy, followed by laser in situ keratomileusis 2 years later for high
      astigmatism correction in both eyes. During CK, a corneal perforation occurred in
      the right eye; during the postoperative examination, an iris perforation and
      anterior subcapsule opacification were seen beneath the perforation site. The
      perforation was managed with a bandage contact lens and an antibiotic-steroid
      ointment; it had a negative Seidel sign by the third day. The surgery in the left
      eye was uneventful. Three months after the procedure, the uncorrected visual
      acuity was 20/32 and the best corrected visual acuity 20/20 in both eyes with a
      significant improvement in corneal topography. Care must be taken to prevent CK
      treated spots from coinciding with areas in the corneal stroma that might have
      been altered by previous refractive procedures.

PMID- 14709314
TI  - Favorable outcome using a black diaphragm intraocular lens for traumatic aniridia
      with total iridectomy.
AB  - A 25-year-old man had a penetrating injury to the left eye. Ocular examination
      revealed a full-thickness corneal laceration, total aniridia, anterior capsule
      rupture, and microscopic hyphema. Ten days after the immediate primary-repair
      surgery, aspiration of the lens secondary to traumatic cataract was performed.
      Four months later, a black diaphragm intraocular lens was implanted.
      Postoperatively, the best corrected visual acuity was 20/20 in both eyes.
      Multifocal spectacles were prescribed to provide the near and far vision required
      for the patient's job. Normal intraocular pressure and acceptable photophobia
      were noted during the 18-month follow-up.

PMID- 14709315
TI  - Suture fixation of an intraocular lens combined with pars plana vitrectomy and
      gas tamponade.
AB  - We describe suturing an intraocular lens (IOL) after pars plana lensectomy and
      vitrectomy combined with gas tamponade in 4 patients with vitreoretinal disease
      and subluxated lenses that could not be managed with capsular tension rings. The
      IOL haptics were sutured before the fluid-gas exchange in a horizontal (case 1),
      oblique (cases 2 and 4), and vertical (case 3) manner. In a case of unavoidable
      horizontal fixation due to limited scleral space, the upper part of the IOL
      tilted anteriorly postoperatively because of the enhanced effect of the gas
      bubble. A peripheral anterior iris synechia also occurred. The IOL remained well
      positioned in cases with oblique and vertical fixations, and no other
      complications occurred. Careful preoperative planning of the surgical design can
      help avoid unnecessary horizontal fixation.

PMID- 14709316
TI  - Injection of an intraocular lens without an injector.

PMID- 14709317
TI  - Pseudokeratoprosthesis after corneal melt in a pseudophakic eye.

PMID- 14709318
TI  - Water modulation of lens epithelial cells during cataract surgery.

PMID- 14709321
TI  - Molecular physiology of P2 receptors in the central nervous system.
AB  - Neurons of the central nervous system (CNS) are endowed with ATP-sensitive
      receptors belonging to the P2X (ligand-gated cationic channels) and P2Y (G
      protein-coupled receptors) types. Whereas a number of P2X receptors mediate fast
      synaptic responses to the transmitter ATP, P2Y receptors mediate either slow
      changes of the membrane potential in response to non-synaptically released ATP or
      the interaction with receptors for other transmitters. To date seven P2X and
      seven P2Y receptors of human origin have been molecularly identified and
      functionally characterized. P2X subunits may occur as homooligomers or as
      heterooligomeric assemblies of more than one subunit. P2X(7) subunits do not form
      heterooligomeric assemblies and are unique in mediating apoptosis and necrosis of
      glial cells and possibly also of neurons. The P2X(2), P2X(4), P2X(4)/P2X(6) and
      P2Y(1) receptors appear to be the predominant neuronal types. The localisation of
      these receptors may be at the somato-dendritic region (postsynaptic) or at the
      nerve terminals (presynaptic). Postsynaptic P2 receptors appear to be mostly
      excitatory, while presynaptic P2 receptors may be either excitatory (P2X) or
      inhibitory (P2Y). Since in the CNS the stimulation of a single neuron may
      activate multiple networks, a concomitant stimulation of facilitatory and
      inhibitory circuits as a result of ATP release is also possible. Finally, the
      enzymatic degradation of ATP may lead to the local generation of adenosine which
      can modulate via A(1) or A(2A) receptor-activation the ATP effect.

PMID- 14709322
TI  - Induction of proteins involved in multidrug resistance (P-glycoprotein, MRP1,
      MRP2, LRP) and of CYP 3A4 by rifampicin in LLC-PK1 cells.
AB  - P-glycoprotein, multidrug resistance-related proteins (MRPs) and lung resistance
      related protein (LRP) are involved in multidrug resistance in tumor cells but are
      also expressed in normal tissues. In the LLC-PK(1) tubular renal cell line, a 15
      day treatment with 25 microM rifampicin significantly increased the mRNA levels
      of P-glycoprotein, MRP1, MRP2, LRP and cytochrome P450 3A4 (CYP 3A4). Western
      blot analysis confirmed a moderate increase in the expression of P-glycoprotein
      and MRP2, but not MRP1 also at the protein level. The intracellular uptake of
      doxorubicin was significantly lower in rifampicin pretreated cells. A
      pretreatment with 6-[82S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic
      acid]cyclosporin D, valspodar (PSC 833), a specific inhibitor of P-glycoprotein,
      with (3-(3-(2-(7-chloro-2-quinidinyl)ethenyl-phenyl)((3-diimethyl amino-3oxo
      propyl)thio)methyl)thio)propanoic acid, sodium salt (MK-571), a specific
      inhibitor of MRP1, and with verapamil, that inhibits both proteins, significantly
      increased doxorubicin cell accumulation in rifampicin pretread cells. In
      rifampicin treated cells cultured on porous membranes, doxorubicin showed a
      polarized transport, that was reduced by a pretreatment with PSC 833. A chronic
      treatment with rifampicin induces the expression of transport proteins and of CYP
      3A4 and could therefore alter the renal elimination kinetics of drugs that are
      their substrates.

PMID- 14709323
TI  - Amino acid substitutions from an indispensable disulfide bond affect P2X2
      receptor activation.
AB  - The roles of six amino acid residues downward from an extracellular disulfide
      bond involving Cys(224) in rat P2X(2) receptor were examined. When Cys(224) or
      Pro(225) was replaced with alanine, the responsiveness to ATP was lost. When
      Ile(226) was replaced with other hydrophobic amino acids, the responsiveness to
      ATP was reduced or abolished. When Phe(227) was replaced with leucine or
      isoleucine, the responsiveness to ATP was abolished. The responsiveness to ATP
      was moderately decreased with the alanine-substitution for Arg(228) and it was
      markedly decreased with the alanine-substitution for Leu(229). As for the alanine
      substitution for Gly(230), the sensitivity was changed, but the maximal response
      to ATP was not reduced. The results suggested that a precise structure is
      required for amino acid residues close to the disulfide bond and, in general, the
      amino acid residues at odd number positions and those closer to the disulfide
      bond are more influential to the ATP responsiveness.

PMID- 14709324
TI  - Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C
      receptor agonist.
AB  - YM348, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine, showed a
      high affinity for cloned human 5-HT(2C) receptors (K(i): 0.89 nM). The functional
      selectivity for 5-HT(2C) receptors in the 5-HT(2) receptor family was the highest
      among 5-HT(2C) receptor agonists, including m-chlorophenylpiperazine (mCPP) and
      Ro60-0175 ((S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine). Oral
      administration of YM348 induced penile erections and hypolocomotion in rats,
      being completely inhibited by a selective 5-HT(2C) receptor antagonist, SB242084
      (6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy) pyridin-3-yl carbamoyl]
      indoline). The dose-response curve for penile erections, unlike that for
      hypolocomotion, was an inverted U-shape in the dose range of 0.0677-2.03 mg/kg. A
      selective 5-HT(2A) receptor antagonist, MDL100907 (R(+)-alpha-(2,3
      dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol), and a
      selective 5-HT(2B) receptor antagonist, RS-127445 (2-amino-4-(4-fluoronaphth-1
      yl)-6-isopropylpyrimidine), had no effect on the decline in penile erection
      frequency at 2.03 mg/kg of YM348. YM348 did not affect blood pressure at 2.03
      mg/kg. In conclusion, YM348 is a novel, potent and orally active 5-HT(2C)
      receptor agonist, and neither the activation of 5-HT(2A) or 5-HT(2B) receptors
      nor a cardiovascular effect is likely to contribute to the inverted U-shape dose
      response curve for penile erections.

PMID- 14709325
TI  - In vivo effects of aripiprazole on cortical and striatal dopaminergic and
      serotonergic function.
AB  - In vivo microdialysis was used to monitor the effects of oral aripiprazole and
      olanzapine on basal extracellular concentrations of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole
      acetic acid (5-HIAA) in the medial prefrontal cortex and striatum of conscious,
      freely moving rats. Acute aripiprazole administration did not affect dopamine
      output, but produced moderate increases in DOPAC and HVA concentrations, in
      medial prefrontal cortex or striatum of drug-naive rats. Similarly, aripiprazole
      did not affect dopamine output but produced moderate elevations in DOPAC and HVA
      concentrations in the striatum of chronic aripiprazole-pretreated rats.
      Olanzapine produced comparatively larger elevations in dopamine, DOPAC, and HVA
      in both regions, which, in the striatum, were diminished after chronic olanzapine
      exposure. Aripiprazole reduced extracellular 5-HIAA concentrations in the medial
      prefrontal cortex and striatum of drug-nai;ve rats, but not in chronic
      aripiprazole-pretreated rats. Together, these data provide in vivo evidence of
      aripiprazole-induced changes in forebrain dopaminergic and serotonergic function
      that may reflect its partial agonist activity at presynaptic dopamine D(2) and 5
      HT(1A) receptors and antagonist activity at 5-HT(2A) receptors.

PMID- 14709326
TI  - Behavioral mechanisms underlying inhibition of food-maintained responding by the
      cannabinoid receptor antagonist/inverse agonist SR141716A.
AB  - This study investigated the possible behavioral mechanisms underlying the
      anorectic effect of the cannabinoid CB(1) receptor antagonist/inverse agonist N
      (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted
      and trained to emit stable responding in daily 10-min, fixed ratio 10 food
      reinforced operant sessions. Under these conditions, as well as under free
      feeding conditions, SR141716A inhibited food-maintained responding (ED(50) values
      ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A
      suppressed intracranial self-stimulation with a potency which was slightly lower
      than the anorectic potency (ED(50): 4.50 mg/kg). As assessed during a 10-min test
      period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the
      observed inhibition of operant behavior is not a direct consequence of impairment
      of locomotor activity. SR141716A, however, attenuated saccharin-preference in a
      conditioned taste aversion paradigm (ED(50): 6.45 mg/kg). Although the data
      support the suggestion that the anorectic effect of SR141716A results from an
      attenuating effect on the rewarding effect of food, the contribution of drug
      induced aversion/malaise cannot be excluded.

PMID- 14709327
TI  - Ritanserin counteracts both rat vacuous chewing movements and nigro-striatal
      tyrosine hydroxylase-immunostaining alterations induced by haloperidol.
AB  - The effect of subchronic co-administration of ritanserin (1.5 mg/kg, i.p., twice
      a day) and haloperidol (1 mg/kg, i.p., twice a day) on rat vacuous chewing
      movements and on tyrosine hydroxylase-immunostaining was investigated. Ritanserin
      significantly reduced rat vacuous chewing movements observed following 2, 3 and 4
      weeks of haloperidol administration and after 5 days of haloperidol withdrawal.
      Furthermore, ritanserin prevented the reduction of striatal tyrosine hydroxylase
      immunostaining and the shrinkage of nigral dopaminergic cell bodies induced by
      haloperidol. The present results indicate that ritanserin may possess protective
      properties on both dopaminergic nigro-striatal neuron alterations and vacuous
      chewing movements induced by haloperidol, and provide further evidence indicating
      a possible association between these two haloperidol-induced effects.

PMID- 14709328
TI  - Role of Rho-kinase in maintaining airway smooth muscle contractile phenotype.
AB  - This study aims to investigate the role of Rho-kinase in phenotype switching and
      proliferation of bovine tracheal smooth muscle. To induce different phenotypic
      states, bovine tracheal smooth muscle strips were cultured (8 days) in 10% foetal
      bovine serum (foetal bovine serum, less contractile phenotype) or insulin (1
      microM, hypercontractile phenotype) and compared to strips cultured in serum-free
      medium. In contraction experiments, the Rho-kinase inhibitor (+)-(R)-trans-4-(1
      aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide (Y-27632, 1 microM) decreased
      sensitivity to methacholine and KCl and lowered maximal responsiveness to KCl in
      all strips irrespective of the phenotype present. To investigate the effects of
      Rho-kinase bovine tracheal smooth muscle phenotypic regulation, strips were
      pretreated with Y-27632 (1 microM) for 8 days. This resulted in a decreased
      maximal contractility to both methacholine and KCl, quantitatively comparable to
      the decrease in contractility induced by platelet-derived growth factor (PDGF, 10
      ng/ml). The combination of Y-27632 and PDGF responded additively. Y-27632 did not
      affect basal or PDGF-induced bovine tracheal smooth muscle cell proliferation,
      determined both as increases in [3H]thymidine incorporation and cell number.
      Inhibitors of the p42/p44 mitogen-activated protein kinase (MAPK) pathway, the
      p38 MAPK pathway and the phosphatidyl inositol (PI) 3-kinase pathway all
      inhibited PDGF-induced proliferation and phenotype changes. These results show
      that the functional contribution of Rho-kinase to bovine tracheal smooth muscle
      contraction is not dependent on phenotypic state. In addition, Rho-kinase is not
      involved in phenotypic modulation or proliferation induced by PDGF, whereas
      p42/p44 MAPK, p38 MAPK and PI 3-kinase are. Rho-kinase is, however, a major
      regulator involved in the basal maintenance of contractility in bovine tracheal
      smooth muscle.

PMID- 14709330
TI  - Arf GAPs: multifunctional proteins that regulate membrane traffic and actin
      remodelling.
AB  - The ADP-ribosylation factor (Arf) Arf GTPase-activating proteins (GAPs) are a
      family of proteins that induce hydrolysis of GTP bound to Arf. A conserved domain
      containing a zinc finger motif mediates catalysis. The substrate, Arf.GTP,
      affects membrane trafficking and actin remodelling. Consistent with activity as
      an Arf regulator, the Arf GAPs affect both of these pathways. However, the Arf
      GAPs are likely to have Arf-independent activities that contribute to their
      cellular functions. Structures of the Arf GAPs are diverse containing catalytic,
      protein-protein interaction and lipid interaction domains in addition to the Arf
      GAP domain. Some Arf GAPs have been identified and characterized on the basis of
      activities other than Arf GAP. Here, we describe the Arf GAP family, enzymology
      of some members of the Arf GAP family and known functions of the proteins. The
      results discussed illustrate roles for both Arf-dependent and -independent
      activities in the regulation of cellular architecture.

PMID- 14709329
TI  - Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma,
      reduces acute inflammation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid and thyroid hormone receptors. The PPAR-gamma
      receptor subtype appears to play a pivotal role in the regulation of cellular
      proliferation and inflammation. The thiazolidinedione rosiglitazone (Avandia) is
      a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, that was
      recently approved by the Food and Drug Administration for treatment of type II
      diabetes mellitus. In the present study, we have investigated the effects of
      rosiglitazone in animal models of acute inflammation (carrageenan-induced paw
      oedema and carrageenan-induced pleurisy). We report here for the first time that
      rosiglitazone (given at 1, 3 or 10 mg/kg i.p. concomitantly with carrageenan
      injection in the paw oedema model, or at 3, 10 or 30 mg/kg i.p. 15 min before
      carrageenan administration in the pleurisy model) exerts potent anti-inflammatory
      effects (e.g. inhibition of paw oedema, pleural exudate formation, mononuclear
      cell infiltration and histological injury) in vivo. Furthermore, rosiglitazone
      reduced: (1) the increase in the staining (immunohistochemistry) for
      nitrotyrosine and poly (ADP-ribose) polymerase (PARP), (2) the expression of
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), intercellular
      adhesion molecules-1 (ICAM-1) and P-selectin in the lungs of carrageenan-treated
      rats. In order to elucidate whether the protective effect of rosiglitazone is
      related to activation of the PPAR-gamma receptor, we also investigated the effect
      of a PPAR-gamma antagonist, bisphenol A diglycidyl ether (BADGE), on the
      protective effects of rosiglitazone. BADGE (30 mg/kg i.p.) administered 30 min
      prior to treatment with rosiglitazone significantly antagonized the effect of the
      PPAR-gamma agonist and thus abolished the anti-inflammatory effects of
      rosiglitazone. We propose that rosiglitazone and other potent PPAR-gamma agonists
      may be useful in the therapy of inflammation.

PMID- 14709331
TI  - Prostaglandin F2alpha increases glucose transport in 3T3-L1 adipocytes through
      enhanced GLUT1 expression by a protein kinase C-dependent pathway.
AB  - The effect of prostaglandin F2alpha (PGF2alpha) on glucose transport in
      differentiated 3T3-L1 adipocytes was examined. Whereas PGF2alpha had little
      influence on insulin-stimulated 2-deoxyglucose uptake, it increased basal glucose
      uptake in a time- and dose-dependent manner, reaching maximum at approximately 8
      h. The long-term effect of PGF2alpha on glucose transport was inhibited by both
      cycloheximide and actinomycin D. In concord, while the content of GLUT4 protein
      was not altered, immunoblot and Northern blot analyses revealed that both GLUT1
      protein and mRNA levels were increased by exposure of cells to PGF2alpha. The
      effect of PGF2alpha on glucose uptake was inhibited by GF109203X, a selective
      protein kinase C (PKC) inhibitor. In addition, in cells depleted of
      diacylglycerol-sensitive PKC by prolonged treatment with 4beta-phorbol 12beta
      myristate 13alpha-acetate (PMA), the stimulatory effects of PGF2alpha on glucose
      transport and GLUT1 mRNA accumulation were both inhibited. In accord, PMA was
      shown to stimulate GLUT1 mRNA accumulation. To further investigate if PKC may be
      activated by PGF2alpha, we tested several diacylglycerol-sensitive PKC isozymes
      and found that PGF2alpha was able to activate PKCepsilon. Taken together, these
      results indicate that PGF2alpha may enhance glucose transport in 3T3-L1
      adipocytes by stimulating GLUT1 expression via a PKC-dependent mechanism.

PMID- 14709332
TI  - Association of PI 3-K with tyrosine phosphorylated Vav is essential for its
      activity in neutrophil-like maturation of myeloid cells.
AB  - The importance of the Vav family of signal transduction molecules in
      hematopoietic cells has long been acknowledged, even though its role and its
      regulatory mechanism are not completely understood. We have previously
      demonstrated that tyrosine-phosphorylated Vav, also located inside the nucleus of
      myeloid cells, is up-regulated during maturation of promyelocytic precursors
      induced by all-trans-retinoic acid (ATRA). Here, we report that the tyrosine
      phosphorylation of Vav during granulocytic maturation is dependent on the
      tyrosine kinase Syk and is essential for the morphological changes of the cell
      nucleus. These ATRA-induced events are independent on the guanine nucleotide
      exchange activity of Vav. We also found that, in differentiating cells, and in
      both cytoplasmic and nuclear compartments, tyrosine phosphorylated Vav associates
      with the regulatory subunit of phosphoinositide 3-kinase (PI 3-K). The Vav/p85
      interaction is essential for the ATRA-induced PI 3-K activity and for association
      of PI 3-K with actin, particularly in the nucleus. Our data indicate an
      unprecedented crucial function for Vav in modulating the morphological maturation
      process of myeloid cells in a GDP-GTP exchange factor (GEF)-independent manner
      and suggest a role of Vav as an adaptor protein responsible of targeting PI 3-K
      to its intranuclear substrates.

PMID- 14709333
TI  - Systematic identification of immunoreceptor tyrosine-based inhibitory motifs in
      the human proteome.
AB  - Immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are short sequences of
      the consensus (ILV)-x-x-Y-x-(LV) in the cytoplasmic tail of immune receptors. The
      phosphorylation of tyrosines in ITIMs is known to be an important signalling
      mechanism regulating the activation of immune cells. The shortness of the motif
      makes it difficult to predict ITIMs in large protein databases. Simple pattern
      searches find ITIMs in approximately 30% of the protein sequences in the RefSeq
      database. The majority are false positive predictions. We propose a new database
      search strategy for ITIM-bearing transmembrane receptors based on the use of
      sequence context, i.e. the predictions of signal peptides, transmembrane helices
      (TMs) and protein domains. Our new protocol allowed us to narrow down the number
      of potential human ITIM receptors to 109 proteins (0.7% of RefPep). Of these, 36
      have been described as ITIM receptors in the literature before. Many ITIMs are
      conserved between orthologous human and mouse proteins which represent novel ITIM
      receptor candidates. Publicly available DNA array expression data revealed that
      ITIM receptors are not exclusively expressed in blood cells. We hypothesise that
      ITIM signalling is not restricted to immune cells, but also functions in diverse
      solid organs of mouse and man.

PMID- 14709334
TI  - Cooperation between PKC-alpha and PKC-epsilon in the regulation of JNK activation
      in human lung cancer cells.
AB  - Phorbol esters can induce activation of two mitogen-activated protein kinase
      (MAPK) pathways, the extracellular signal-regulated kinase (ERK) pathway and the
      c-Jun N-terminal kinase (JNK) pathway. Unlike ERK activation, JNK activation by
      phorbol esters is somehow cell-specific. However, the mechanism(s) that
      contribute to the cell-specific JNK activation remain elusive. In this study, we
      found that phorbol 12-myristate 13-acetate (PMA) induced JNK activation only in
      non-small cell lung cancer (NSCLC) cells, but not in small cell lung cancer
      (SCLC) cells, whereas ERK activation was detected in both cell types. In NSCLC
      cells, PMA induced JNK activation in a time- and dose-dependent manner. JNK
      activation was attenuated by protein kinase C (PKC) down-regulation through
      prolonged pre-treatment with PMA and significantly inhibited by PKC inhibitors
      Go6976 and GF109203X. Subcellular localization studies demonstrated that PMA
      induced translocation of PKC-alpha, -betaII, and -epsilon isoforms, but not PKC
      delta, from the cytosol to the membrane. Analysis of various PKC isoforms
      revealed that PKC-epsilon was exclusively absent in the SCLC cell lines tested.
      Ectopic expression of PKC-epsilon in SCLC cells restored PMA activation of JNK
      signaling only in the presence of PKC-alpha, suggesting that PKC-alpha and PKC
      epsilon act cooperatively in regulating JNK activation in response to PMA.
      Furthermore, using dominant negative mutants and pharmacological inhibitors, we
      define that a putative Rac1/Cdc42/PKC-alpha pathway is convergent with the PKC
      epsilon/MEK1/2 pathway in terms of the activation of JNK by PMA.

PMID- 14709336
TI  - Prostacyclin receptor-mediated activation of extracellular signal-regulated
      kinases 1 and 2.
AB  - The prostacyclin mimetic cicaprost increased phosphorylation of extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) in Chinese hamster ovary cells
      transiently expressing human (hIP-CHO) or mouse prostacyclin (mIP-CHO) receptors,
      but not in human neuroblastoma SK-N-SH cells or rat/mouse neuroblastoma-glioma
      NG108-15 cells which endogenously express IP receptors. Cicaprost stimulated
      ERK1/2 activity in hIP-CHO and mIP-CHO cells with EC50 values of 60 and 83 nM,
      respectively, and this response was significantly inhibited by protein kinase C
      inhibitors and agents which elevate cyclic AMP. A poor correlation was discovered
      between the level of ERK1/2 activity and the ability of agents to increase or
      decrease cyclic AMP production. The potent inhibitory effect of 3-isobutyl-1
      methyl xanthine on cicaprost-stimulated phospho-ERK1/2 may be due to inhibition
      of phosphoinositide 3-kinase. Therefore, IP receptor-mediated activation of
      ERK1/2 in CHO cells occurs through a Gq/11/protein kinase C-dependent and a
      phosphoinoside 3-kinase-dependent process which is insensitive to IP receptor
      generated cyclic AMP.

PMID- 14709335
TI  - Interleukin-17 signal transduction pathways implicated in inducing matrix
      metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes.
AB  - Interleukin (IL)-17 promotes cartilage breakdown by inducing matrix
      metalloproteinases (MMPs) and aggrecanases (a disintegrin and metalloproteinase
      with thrombospondin motif, ADAMTS) in arthritic joints. We investigated IL-17
      signaling pathways inducing MMP-3, MMP-13 and ADAM-TS4 genes in bovine articular
      chondrocytes. IL-17 stimulated phosphorylation of extracellular signal-regulated
      kinase (ERK), protein 38 (p38) and c-Jun N-terminal kinase (JNK). ERK pathway
      inhibitors, PD98059 and U0126, down-regulated IL-17-induced MMP and ADAM-TS4 gene
      expression. Protein 38 and JNK pathway inhibitors, SB203580 and SP600125, also
      reduced induction of these genes. Antioxidants and activating protein-1
      transcription factor inhibitors, nordihydroguaiaretic acid and N-acetyl-L
      cysteine (NAC) suppressed MMP and ADAM-TS4 genes. Similarly, nuclear factor kappa
      B (NF-kappaB) pathways inhibitors curcumin and Bay-11-7085 also blocked their
      induction. Thus MMP-3, MMP-13 and ADAM-TS4 genes are coordinately up-regulated by
      IL-17 via MAP kinases, activating protein-1 (AP-1) and NF-kappaB mediators, which
      could be targeted for reducing IL-17-triggered cartilage damage.

PMID- 14709337
TI  - Potentiation of signal transduction mitogenesis and cellular proliferation upon
      binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate
      cancer cells.
AB  - The alpha2-macroglobulin signalling receptor is upregulated in highly metastatic
      1-LN prostate cancer cells. Stimulation of 1-LN cells with activated alpha2
      macroglobulin (alpha2M*) caused a two- to threefold increase in [3H]thymidine
      uptake and cell number. These events require the Ras-dependent MAPK and PI 3
      kinase/Akt signalling cascades. Incubation of 1-LN cells with alpha2M* induced
      Grb2, shc, sos and Raf-1 expression, as well as phosphorylation of MEK 1/2, ERK
      1/2, p38 MAPK and JNK. This treatment also increased PI 3-kinase activation, PDK1
      expression, Akt phosphorylation and p70s6k phosphorylation. Levels of the early
      gene products c-fos protein and thymidylate synthase were comparably increased.
      Exposure of 1-LN cells to alpha2M* significantly raised the levels of
      phosphorylated CREB by about 15-20 min and phosphorylated p53 by about 60-90 min
      of incubation. We conclude that the growth regulatory effects of ligating the
      alpha2M* signalling receptor on 1-LN cells are exerted via the onset and
      crosstalk between the Ras-dependent MAPK and PI 3-kinase/Akt signalling cascades.

PMID- 14709338
TI  - Dynamin-2 associates with the dopamine receptor signalplex and regulates
      internalization of activated D2 receptors.
AB  - Dopamine receptors (DRs) are implicated in modulating a variety of important
      neuronal processes including those involved in development and plasticity.
      Although dopamine receptors are known to be internalized in response to ligand
      activation, the mechanisms regulating this process have not been clearly defined.
      Here, we show that D2 dopamine receptors (D2Rs) undergo dynamin-2-dependent
      internalization in response to agonist treatment. Using a cleavable biotin assay
      to quantify receptor internalization, we found that expression of dynamin-2
      mutants defective in GTPase function virtually abolished agonist-induced D2R
      internalization. In contrast, expression of a dynamin-1 mutant did not alter D2R
      internalization. In human embryonic kidney (HEK) 293 cells and primary striatal
      neurons, dynamin-2 was found to localize to sites of D2R internalization.
      Dynamin/D2R association was examined in adult rat forebrain using subcellular
      fractionation and coimmunoprecipitation methods. D2Rs and dynamin-2 were
      coexpressed in non-synaptosomal fractions, and dynamin-2 was found to
      coimmunoprecipitate with the D2R signalling complex (signalplex). Taken together,
      our findings suggest that dynamin-2 regulates D2R internalization and thus is
      likely to play an important role in D2R mediated dopaminergic transmission.

PMID- 14709339
TI  - Protein kinase C modulates negatively the hepatocyte growth factor-induced
      migration, integrin expression and phosphatidylinositol 3-kinase activation.
AB  - Previously, we reported that, in hepatocyte growth factor (HGF)-induced HepG2
      cells, protein kinase C (PKC) decreased the duration of intensive Erk1/Erk2 MAP
      kinase activation. This study shows that the inhibition of PKC enhanced
      significantly the HGF-induced integrin expression. Beside the prolonged
      activation of Erk1/Erk2, the activity of phosphatidylinositol 3-kinase (PI 3K)
      was required for growth factor-induced integrin expression. PI 3-kinase was
      activated to a higher extent in response to HGF than to epidermal growth factor
      (EGF), though the activation was transient in both cases. In EGF-induced cells,
      PI 3K activation was terminated by the loss of phosphotyrosine docking sites for
      PI 3K. To the contrary, the decrease of PI 3K activation, which followed the HGF
      induced increase was not accompanied by the loss of phosphotyrosine docking sites
      and was prevented by the inhibition of PKC. The negative modulator effects of PKC
      on integrin expression and PI 3-kinase activation correlated with its ability to
      limit the HGF-induced motogen response.

PMID- 14709340
TI  - Translocated in liposarcoma (TLS) is a substrate for fibroblast growth factor
      receptor-1.
AB  - Binding of fibroblast growth factor (FGF) to the high affinity receptor-1 (FGFR
      1) leads to activation of its endogenous tyrosine kinase activity. A number of
      substrates for the FGFR-1 kinase have been identified. Among those, FGF receptor
      substrate-2 (FRS-2) was identified by virtue of its interaction with p13suc, a
      yeast protein involved in cell cycle regulation. We have used immobilized p13suc
      to identify a new substrate for FGRF-1, which is identical to "translocated in
      liposarcoma" (TLS). TLS is a RNA/DNA-binding protein which occurs in fusion
      products with different transcription factors in a variety of solid tumours. We
      show that TLS is tyrosine phosphorylated in intact cells by a number of different
      growth factors, indicating a role in growth regulation.

PMID- 14709341
TI  - Suppressive silver methods--a tool for identifying axotomy-induced neuron
      degeneration.
AB  - Suppressive silver methods evolved from empirical observations about 50 years ago
      that argyrophilia of normal nerve fibers can be suppressed by a short period of
      oxidation of tissue sections, whereas degenerating nerve fibers in the same
      preparations were still clearly visible. Based on this property, suppressive
      silver impregnation became the main technique for investigating pathways in the
      central nervous system until the early 1970s. Suppressive silver methods were
      also found to visualize degenerating nerve cell bodies, in addition to
      degenerating nerve fibers. This possibility has given these methods an important
      place among current tools for identifying neuronal degeneration in trauma,
      disease and toxicity. In this article we demonstrate and review the usefulness of
      suppressive silver methods in identifying neurons undergoing degeneration as a
      result of peripheral or central axon injury in immature animals. The
      documentation is based on previously published data from experiments in which
      silver impregnation was used to demonstrate degeneration of motoneurons following
      pure motor axon injury or mixed peripheral nerve injury, as well as on new
      results on degeneration-induced argyrophilia in the inferior olive following
      cerebellar lesions. We find that silver precipitates resulting from these
      injuries are localized either to the entire neuronal cytoplasm, to a few
      (typically two) intranuclear bodies, or to both sites. The findings are discussed
      in relation to morphological features of apoptosis, necrosis and retrograde
      neuronal responses. We suggest that suppressive silver methods allow
      visualization of different processes of neuronal degeneration, and therefore may
      be a useful adjunct for identifying axotomy-induced neuronal degeneration.

PMID- 14709342
TI  - Dual separate pathways for sensory and hedonic aspects of taste.
AB  - It is proposed that in the gustatory system there exist separate sensory and
      hedonic (reward-aversion) representations in each of the primary structures in
      which processing of gustatory stimuli occurs. Anatomical and physiological data
      are used to determine putative separate sensory and hedonic representations in
      the nucleus of the solitary tract, parabrachial complex, gustatory thalamus, and
      cortical gustatory areas. In the nucleus of the solitary tract, the sensory
      representation is located in the rostralmost part of the nucleus, and the hedonic
      representation most probably in the intermediate parts. In the parabrachial
      complex, the sensory representation is located in the central medial and ventral
      lateral subnuclei, and in the waist area, and the hedonic representation in the
      inner division of the external lateral subnucleus and in the external medial
      subnucleus. In the rodent gustatory thalamic relay, the sensory representation
      occurs in the dorsal lateral parts of the nucleus, and the hedonic representation
      in the ventromedial parts. In rodent gustatory insular cortex, the sensory
      representation is found in anterior parts of the gustatory area, and the hedonic
      representation caudal to the sensory representation. The function of the separate
      sensory and hedonic representations is discussed in relation to the conditioned
      taste aversion paradigm.

PMID- 14709343
TI  - Morphine actions in the rat forebrain: role of protein kinase C.
AB  - Acute administration of morphine induces expression of the immediate-early gene
      (IEG) c-Fos in dorsomedial striatum, portions of cerebral cortex, and in several
      midline-intralaminar thalamic nuclei, partly via a trans-synaptic mechanism that
      involves activation of glutamate receptors. Because activation of protein kinase
      C (PKC) may occur following the activation of glutamate receptors, we determined
      whether pharmacological inhibition of PKC would attenuate morphine-induced c-Fos
      expression, and whether acute administration of morphine would induce
      translocation of PKC. The selective PKC antagonist NPC 15437 given 30 min prior
      to morphine significantly decreased morphine-induced c-Fos expression in striatum
      and cingulate cortex, but not in centrolateral thalamus. In another experiment,
      rats were given an acute dose of morphine, and immunocytochemical analysis was
      performed for the betaI and betaII isoforms of PKC. Morphine induced a rapid and
      transient translocation of PKC betaII, but not betaI, from perinuclear spots to
      plasma membrane in numerous cortical and striatal neurons. Prior administration
      of naloxone blocked this response. Ultrastructural studies confirmed
      translocation from Golgi apparatus to plasma membrane 15 min after morphine
      injection. Double immunocytochemistry at the light microscopic level demonstrated
      co-localization of translocated PKC betaII and c-Fos in some cortical neurons 90
      min after morphine injection. These results support a role for PKC, especially
      PKC betaII, in the rapid effects of morphine on the brain.

PMID- 14709344
TI  - Angiotensin II attenuates chemical hypoxia-induced caspase-3 activation in
      primary cortical neuronal cultures.
AB  - In this study we determined whether caspase-3 is required in mouse cortical
      neurons for sodium azide-mediated apoptosis. Primary cortical neuronal cultures
      were treated with a cell permeable caspase-3 inhibitor, DEVD (1 nM-100 fM), prior
      to sodium azide-induced hypoxia. Treatment with the caspase-3 inhibitor resulted
      in a dose-dependent decrease in apoptosis, suggesting that sodium azide-induced
      apoptosis is mediated through a caspase-3 dependent pathway. Levels of cytochrome
      c release and caspase-3 cleavage were assayed by Western analysis. Cytochrome-c
      release and caspase-3 cleavage were observed at 5 h (85.3+/-5.8%) and 8 h (53.4+/
      14.9%), respectively. We have previously reported that angiotensin II, acting
      through the AT(2) receptor subtype, protects cultured mouse cortical neurons from
      sodium azide-induced apoptosis. We also examined whether the protective effect of
      angiotensin II is mediated through modulation of caspase-3. Pre-treatment of
      cells with angiotensin II and the AT(1) receptor antagonist, losartan, reduced
      levels of sodium azide-induced caspase-3 cleavage by 95.0+/-4.0%. Cells pre
      treated with the AT(2) receptor antagonist, PD123319 showed a smaller reduction
      of caspase-3 cleavage (53.8+/-3.4%). Our findings indicate that sodium azide
      induced apoptosis is caspase-3 dependent and that angiotensin II protects
      cortical neurons from chemical-induced apoptosis by reducing caspase-3 cleavage.

PMID- 14709345
TI  - Beta-adrenoceptor modulation of transiently overexpressed alpha 2-adrenoceptors
      in brain and peripheral tissues: cellular mechanisms underlying the developmental
      toxicity of terbutaline.
AB  - Terbutaline, a selective beta(2)-adrenoceptor (beta(2)AR) agonist, is widely used
      as a tocolytic to arrest preterm labor but recent studies indicate that excessive
      betaAR stimulation can alter the expression and function of other
      neurotransmitter receptors that are essential to fetal/neonatal development. In
      many immature tissues, alpha(2)-adrenergic receptors (alpha(2)ARs) are
      overexpressed and the receptors are thought to play a role in cell proliferation
      and architectural assembly. We evaluated whether betaAR agonists perturb the
      expression of alpha(2)ARs in central and peripheral tissues during various
      developmental stages in the fetal and neonatal rat. In peripheral tissues (heart,
      liver, kidney) administration of terbutaline (10mg/kg s.c. for 4 days) elicited
      decrements in alpha(2)AR expression only during a critical developmental window
      that differed for each tissue; terbutaline was more effective than isoproterenol,
      a mixed beta(1)/beta(2) agonist. Neonatal destruction of sympathetic nerves with
      6-hydroxydopamine (6-OHDA) had a biphasic effect, initially reducing alpha(2)ARs
      but subsequently elevating receptor expression. In contrast to the effects in the
      periphery, terbutaline administration promoted alpha(2)AR expression in neonatal
      brain regions with effects preferential to males. As the rat is an altricial
      species, these results during late gestation and the early neonatal period
      indicate that betaAR input modulates alpha(2)AR expression during developmental
      stages in which betaAR tocolytics are likely to be used. Disruption of alpha(2)AR
      expression and function may therefore contribute to adverse effects that have
      been noted in the offspring of pregnant women treated with terbutaline.

PMID- 14709346
TI  - A neurobehavioral screening of the ckr mouse mutant: implications for an animal
      model of schizophrenia.
AB  - A model of schizophrenia, the chakragati (ckr) mouse was serendipitously created
      as a result of a transgenic insertional mutation. The apparent loss-of-function
      of an endogenous gene produced mice that, when homozygous, displayed an abnormal
      circling behavior phenotype. To determine whether this phenotype could be
      corrected by atypical antipsychotics, we compared the effects of clozapine and
      olanzapine on rotational turns and hyperactivity. Both of these drugs
      successfully ameliorated circling behavior and hyperactivity in homozygous mice.
      The increased motor activity of these mutant mice was both qualitatively and
      quantitatively similar to that observed in wild-type animals treated with
      dizocilpine, an N-methyl-D-aspartate receptor antagonist that produces behaviors
      resembling positive symptoms of schizophrenia. Mice either homozygous or
      heterozygous for the mutation also displayed enlargement of the lateral
      ventricles, which was accompanied only in the homozygous genotype by a loss of
      individual myelinated axons in the striatum and agenesis of the corpus callosum.
      These structural brain deficits were selective in that the nigro-striatal
      dopamine system was normal in these homozygous mice. In addition, two types of
      interneurons in the neostriatum, namely those producing acetylcholine or nitric
      oxide synthase were also devoid of significant structural abnormalities. These
      results indicate that the ckr mouse mutant could be used as a possible animal
      model to study the pathophysiology of schizophrenia and suggest possible
      strategies for treating the behavioral aspects of this brain disease.

PMID- 14709347
TI  - Non-opioid-dependent anti-inflammatory effects of low frequency
      electroacupuncture.
AB  - Low frequency electroacupuncture, which is commonly used in pain relief, is known
      to induce opioid-mediated analgesia. This study examined the contribution of the
      opioid system in mediating the anti-inflammatory effects of low frequency EA in a
      standard model of acute inflammation, the carrageenan-induced edema model.
      Carrageenan was injected in the hind paw of anesthetized rats and low frequency
      electroacupuncture was applied to acupoints equivalent to Zusanli (St 36) and
      Sanyinjiao (Sp 6) in humans just prior to the induction of inflammation in the
      ipsilateral leg. Induction of Fos protein, reflecting neuronal activation, was
      investigated in the spinal cord with immunohistochemistry. It was found that
      electroacupuncture strongly inhibited the carrageenan-induced edema by over 60%,
      and suppressed the associated Fos expression in the superficial laminae (I-II) of
      the ipsilateral dorsal horn by 50%. Neither the anti-edematous effect nor the
      suppression of Fos expression in the superficial spinal laminae was affected by
      intraperitoneal injection of the opioid antagonist naloxone. These results
      demonstrate that low frequency electroacupuncture is capable of inhibiting
      peripheral inflammation and the associated central neuronal activity via a non
      opioid-dependent mechanism.

PMID- 14709348
TI  - Adaptive morphological changes of neocortical interneurons in response to
      enlarged and more complex pyramidal cells in p21H-Ras(Val12) transgenic mice.
AB  - Morphological features of interneuronal adaptation to an altered, more complex
      neuronal architecture have been investigated in p21H-Ras(Val12) transgenic mice.
      This transgenic strain serves as a model for studying the morphogenetic role of
      the G-protein p21Ras on cortical principal neurons. We have recently demonstrated
      that postmitotic expression of constitutively active p21H-Ras(Val12) in the
      neocortical pyramidal cell population results in increased size and dendritic
      complexity of the affected neurons, leading to an enlarged cortical volume.
      Interneurons do not express the transgene and are therefore excluded from direct,
      intrinsic p21H-Ras(Val12) effects. In the present study, immunolabelling of gamma
      amino-butyric-acid (GABA), and of the calcium-binding proteins parvalbumin,
      calbindin and calretinin revealed that in the transgenic mice local circuit
      neurons are not increased in either somal size or number and their main
      morphological characteristics are preserved. However, the dendritic arbour of
      interneurons was found to be extended, at least in the vertical dimension, to
      follow the cortical expansion. Immunostaining for the vesicular GABA transporter
      revealed a denser inhibitory innervation of p21H-Ras(Val12)-expressing pyramidal
      cell perikarya than in those of wild-type animals, while the overall density of
      inhibitory axon terminals within the cortex was decreased in the transgenic
      animals as a consequence of cortical expansion. The findings of the present study
      demonstrate the morphogenetic capacity of interneurons for adapting to
      morphological alterations of principal neurons in the cerebral cortex.

PMID- 14709349
TI  - Characteristics of nociceptors in the periodontium--an in vitro study in rats.
AB  - Recent studies have indicated that nociceptors can be classified into various
      types according to their physiological properties. These studies have clarified
      that the frequency distribution of various nociceptor types is different among
      body sites and animal species. In the present study, we investigated the
      physiological properties of rat's periodontal nociceptors in an in vitro jaw
      nerve preparation. Responses were recorded from functional single filaments in
      the inferior alveolar nerve. To determine the nociceptor type, calibrated von
      Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five
      subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta
      high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat
      nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C
      high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C
      POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of
      C-innervated nociceptors were found. The present results suggest that periodontal
      nociceptors transmit mainly fast pain, and may thus play a role in rapid
      detection of injure-related stimuli during mastication.

PMID- 14709350
TI  - Leukocytes and coronary heart disease.
AB  - Inflammation has been demonstrated to be an important risk factor for the
      development of cardiovascular events. Patients with elevated white blood cell
      counts have been shown to be in a higher risk of developing acute myocardial
      infarction and acute coronary and vascular events. We review the clinical data of
      high white blood cell counts and the prognosis, and demonstrate several possible
      mechanisms. It is possible that measuring white blood cell count and
      subpopulations could be used for a better way of risk stratification of patients
      admitted with acute vascular events.

PMID- 14709351
TI  - Relationship of circulating C-reactive protein levels to thyroid status and
      cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is
      associated with elevated hsCRP.
AB  - The mechanism(s) by which low circulating levels of thyroid hormones may lead to
      development of premature atherosclerosis remain to be established. These
      mechanisms include indirect effects of thyroid hormones on cardiovascular risk
      factors such as plasma lipoproteins, homocysteine and fibrinogen. High
      sensitivity C-reactive protein (hsCRP) has been identified as an independent
      predictor of cardiovascular events. We presently investigated the relationship
      between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid
      hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers).
      None of these subjects presented a recent history of infection or inflammatory
      disease and those taking drugs known to influence thyroid or hsCRP were excluded.
      Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity
      immunoassay. In the population of non-smokers, plasma FT4 levels were negatively
      and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant
      correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14,
      P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division
      of the population on the basis of FT4 tertiles, the mean level of hsCRP was
      significantly higher in non-smoker patients with the lowest FT4 tertile as
      compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l,
      respectively, P<0.05). No correlation between FT4 levels and CRP was found in
      smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly
      negatively correlated with free thyroxine levels in non-smoker hyperlipidemic
      patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic
      subjects constitute a new biomarker of elevated cardiovascular risk.

PMID- 14709352
TI  - Impairment of vascular function following BCG immunisation is associated with
      immune responses to HSP-60 in the cholesterol-fed rabbit.
AB  - An immune response to heat shock protein (HSP)-60/65 has recently been implicated
      in atherogenesis. The aim of this study was to determine whether this effect may
      be mediated by impairment of endothelial function. Rabbits were injected with
      bacillus Calmette-Guerin (BCG) vaccine (n=12) or saline (n=12). A further
      injection of BCG or saline was administered after 2 weeks. After a further 2
      weeks, animals were fed either a 0.25-1% cholesterol diet or a chow diet for 16
      weeks. Blood cholesterol levels were maintained at 10-12mmol/l by altering the
      dietary cholesterol content. Plasma levels of anti-mycobacterial antibodies rose
      following BCG immunisation, but anti-HSP antibodies developed only in the BCG
      immunised, cholesterol-fed rabbits. Aortic endothelium from cholesterol-fed, but
      not chow-fed, rabbits stained positively for HSP-60, independently of the
      immunisation protocol. Endothelial function was impaired in the BCG immunised,
      cholesterol-fed rabbits as measured by acetylcholine-mediated relaxation of
      isolated non-atherosclerotic carotid artery rings (P<0.05). This impairment was
      positively associated with the level of plasma anti-HSP-60 antibodies (P<0.01).
      These results suggest that BCG immunisation impairs endothelial responses, at
      least in part, by immune responses against mycobacterial and vascular HSP.

PMID- 14709353
TI  - Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in
      apolipoprotein E-knockout mice.
AB  - Atherosclerosis has a close relationship to inflammation, particularly T helper
      type 1 lymphocyte (Th1) response. Interleukin-10 (IL-10), is thought to suppress
      Th1 response. To target therapeutic strategy for atherosclerosis, we tested
      whether IL-10 gene transfer suppresses atherosclerosis in apolipoprotein E
      knockout (apoE-KO) mice. Four-week-old apoE-KO mice were divided into two groups
      and either murine IL-10 cDNA plasmid or empty control vector was transferred to
      the femoral muscle with the use of Hemagglutinating virus of Japan (HVJ)
      liposome. At 1 week after transfection, high cholesterol diet was started and
      continued for 8 weeks. After euthanasia, histological studies of atherosclerotic
      lesions and quantitative RT-PCR for Th1 cytokines (IL-12 and IFN-gamma) in
      spleens were performed. IL-10 cDNA gene transfer to the muscle increased plasma
      IL-10 levels and depressed expression of Th1 cytokines without changing plasma
      cholesterol levels. IL-10 gene transfer significantly reduced the atherosclerotic
      plaque area and the macrophage infiltrated area. IL-12 and IFN-gamma mRNA
      expressions in spleens and plasma IFN-gamma levels were decreased by IL-10 gene
      transfer. Therefore, IL-10 gene transfer changed the Th1 response and suppressed
      atherosclerotic lesion formation in apoE-KO mice. IL-10 could be a new target as
      a therapeutic tool for the treatment of atherosclerosis.

PMID- 14709354
TI  - Rapamycin attenuates atherosclerosis induced by dietary cholesterol in
      apolipoprotein-deficient mice through a p27 Kip1 -independent pathway.
AB  - Activation of immune cells and dysregulated growth and motility of vascular
      smooth muscle cells contribute to neointimal lesion development during the
      pathogenesis of vascular obstructive disease. Inhibition of these processes by
      the immunosuppressant rapamycin is associated with reduced neointimal thickening
      in the setting of balloon angioplasty and chronic graft vessel disease (CGVD). In
      this study, we show that rapamycin elicits a marked reduction of aortic
      atherosclerosis in apolipoprotein E (apoE)-null mice fed a high-fat diet despite
      sustained hypercholesterolemia. This inhibitory effect of rapamycin coincided
      with diminished aortic expression of the positive cell cycle regulatory proteins
      proliferating cell nuclear antigen and cyclin-dependent kinase 2. Moreover,
      rapamycin prevented the normal upregulation of the proatherogenic monocyte
      chemoattractant protein-1 (MCP-1, CCL2) seen in the aorta of fat-fed mice.
      Previous studies have implicated the growth suppressor p27(Kip1) in the
      antiproliferative and antimigratory activities of rapamycin in vitro. However,
      our studies with fat-fed mice doubly deficient for p27(Kip1) and apoE disclosed
      an antiatherogenic effect of rapamycin comparable with that found in apoE-null
      mice with an intact p27(Kip1) gene. Taken together, these findings extend the
      therapeutic application of rapamycin from the restenosis and CGVD models to the
      setting of diet-induced atherosclerosis. Our results suggest that rapamycin
      dependent atheroprotection occurs through a p27(Kip1)-independent pathway that
      involves reduced expression of positive cell cycle regulators and MCP-1 within
      the arterial wall.

PMID- 14709355
TI  - A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi,
      associated with high density lipoprotein deficiency, corneal opacities, planar
      xanthomas, and premature coronary artery disease.
AB  - Familial HDL deficiency (FHD) is a rare autosomal dominant lipoprotein disorder.
      We describe a novel genetic variant of the apolipoprotein A-I (apoA-I) gene
      resulting in FHD. The proband is a 51-year-old woman who was hospitalized due to
      severe heart failure. Her plasma HDL-cholesterol (C) and apoA-I concentrations
      were 0.08mmol/l and 1mg/dl, respectively. She exhibited corneal opacities and
      planar xanthomas on eyelids and elbows. Coronary angiography demonstrated
      extensive obstructions in two major vessels. Genomic DNA sequencing of the
      patient's apoA-I gene revealed a homozygosity for a GC deletion between 5 GC
      repeats in exon 4, creating a frameshift and a stop codon at residue 178. We
      designated this mutation as apoA-I Shinbashi. The proband's father, son, and
      daughter were found to be heterozygous for this mutation and their HDL-C and apoA
      I levels were about half of normal levels, demonstrating a gene dosage effect.
      The father underwent coronary bypass surgery at age of 70 years. Lecithin
      cholesterol acyltransferase (LCAT) activity was decreased by 63% in the
      homozygote and 31% in heterozygotes, respectively. This new case of apoA-I
      deficiency, apoA-I Shinbashi, is the first case involving a single gene defect of
      the apoA-I gene to develop all the characteristics for apoA-I deficiency,
      including premature coronary heart disease.

PMID- 14709356
TI  - Effects of streptozotocin-induced diabetes in apolipoprotein AI deficient mice.
AB  - During the past decade a number of investigators have attempted to develop mouse
      models of diabetic macrovascular disease. Hyperglycemia might increase vascular
      damage because it increases oxidant stress. For this reason we studied animals
      that were deficient in HDL; HDL is widely believed to protect against oxidant
      stress. An inbred line of mice doubly deficient in LDL receptor and apoAI was
      made diabetic with streptozotocin (STZ); control mice had an average glucose of
      7.2+/-2mmol/l and STZ-treated mice had an average glucose of 19.4+/-6.5mmol/l.
      The animals were fed a high cholesterol but low fat diet leading to plasma
      cholesterol levels of 9.4+/-1.6mmol/l in control animals and 10.1+/-1.8mmol/l in
      STZ-treated mice. The control and STZ-treated animals had similar plasma
      lipoprotein profiles. Atherosclerosis assessed at 23 weeks averaged
      38154microm(2) in control and 32962microm(2) in STZ-treated mice. Therefore STZ
      induced diabetes does not alter plasma lipoproteins or atherosclerosis in HDL
      deficient mice.

PMID- 14709357
TI  - Effect of genistein against copper-induced lipid peroxidation of human high
      density lipoproteins (HDL).
AB  - Several studies have demonstrated that the isoflavone genistein exerts a
      protective effect against lipid peroxidation of low density lipoproteins (LDL).
      Aim of our study was to investigate whether genistein protects high density
      lipoproteins (HDL), isolated from normolipemic subjects, against Cu(++)-induced
      lipid peroxidation. Our results demonstrated that genistein exerts an inhibitory
      effect against Cu(++)-induced lipid peroxidation of HDL, as shown by the lower
      increase in the levels of conjugated dienes in lipoproteins oxidized after
      preincubation with different concentrations of genistein (0.5-2.5microM).
      Moreover the analysis of fluorescence emission spectra of tryptophan (Trp) and
      Laurdan (6-dodecanoyl-2-dimethyl-aminonaphthalene) demonstrated that genistein
      prevents the alterations of apoprotein structure and physico-chemical properties,
      associated with Cu(++)-triggered lipid peroxidation of lipoproteins. The
      protective effect exerted by genistein against oxidative damage of lipoproteins
      was realized at concentrations similar to those observed in plasma of human
      subjects consuming a traditional soy diet or receiving a soy supplement.
      Therefore, we suggested that antioxidant activity exerted by genistein against
      lipid peroxidation of HDL in vitro could be of physiological relevance.

PMID- 14709358
TI  - Chronic withdrawal of a high-palatable obesity-inducing diet completely reverses
      metabolic and vascular abnormalities associated with dietary-obesity in the rat.
AB  - Chronic consumption of a high-palatable diet induces obesity and markedly impairs
      arterial relaxation. We have recently reported that endothelial function is only
      partially resorted after acute withdrawal of palatable diet. Therefore, this
      study was designed to investigate the effects of chronic withdrawal of high
      palatable obesity-inducing diet on metabolic and vascular function in rats.
      Wistar rats were fed either standard laboratory chow throughout (controls) or
      given a highly-palatable diet (diet-fed) for 15 weeks; or fed the diet for 8
      weeks and then returned to chow (diet-to-chow) for further 7 weeks before
      sacrifice. Diet-fed rats had higher body weight, fat mass, liver and heart weight
      than both chow-fed and diet-to-chow groups (P<0.01 for all). Compared with chow
      fed and diet-to-chow groups, diet-fed rats had significantly raised fasting
      plasma levels of insulin, leptin and triglycerides levels (each +180%; P<0.0001),
      but not glucose or non-esterified fatty acids. There were no significant
      differences between any metabolic parameters between chow-fed and diet-to-chow
      groups. Mesenteric arteries showed no significant differences between any groups
      in KCl-induced tension generation, while diet-fed groups had significantly higher
      noradrenaline-induced vasoconstriction than both chow-fed and diet-to-chow
      groups. Maximum endothelial-dependent vasorelaxation responses to carbamylcholine
      (CCh) were significantly (by 23%; P<0.001) attenuated in the diet-fed group. This
      defect was abolished in the diet-to-chow group. There were no significant
      differences in endothelium-independent vasorelaxation responses to sodium
      nitroprusside between the three groups. In conclusion, palatable diet induces
      obesity and metabolic abnormalities as well as a marked endothelial dysfunction.
      These abnormalities are completely reversed by chronic withdrawal of the obesity
      inducing high-palatable diet.

PMID- 14709359
TI  - Effects of altering infusion parameters on intimal hyperplasia following local
      catheter-based delivery into the rabbit iliac artery.
AB  - BACKGROUND: Efficient local gene or drug therapy requires optimized application
      modalities to avoid vessel damage, which might lead to increased neointimal
      hyperplasia. Aim of the study was to evaluate different application parameters
      for local delivery using the channeled balloon catheter in order to minimize
      vessel trauma induced by local application. METHODS AND RESULTS: Sixty
      cholesterol fed rabbits were randomly enrolled into twelve groups of different
      local application parameters: group I, application pressure 2atm/application
      volume 1ml physiologic saline; group II, 2atm/2ml; group III, 2atm/5ml; group IV,
      4atm/1ml; group V, 4atm/2ml; group VI, 4atm/5ml. The other six groups received
      Ringer's solution instead of saline. Administration of the solution was randomly
      performed in one iliac artery using the channeled balloon catheter with
      simultaneous balloon angioplasty (8atm). The contralateral iliac artery served as
      a control and was treated with balloon angioplasty only. Four weeks after local
      therapy, calibrated angiography was performed; the animals were sacrificed,
      vessel segments were excised and quantitative morphometric measurements were
      obtained. In none of the animals acute complications, e.g. dissection, thrombosis
      or perforation of the vessel, was noted. Up to an application pressure of 4atm
      and an application volume of 5ml, no significant neointima formation was seen
      compared to arteries which underwent angioplasty only. Additionally, no
      significant differences between saline and Ringer's solution were detected. In a
      multivariate analysis, neither application pressure nor volume were found to have
      a statistically significant influence on the amount of neointimal hyperplasia.
      CONCLUSIONS: Local application of "drugs" using the channeled balloon catheter is
      safe and feasible without significant induction of neointimal hyperplasia
      compared to angioplasty, if an application volume of 5ml and a pressure of 4atm
      is not exceeded.

PMID- 14709360
TI  - Evidence for a reversal with age in the pattern of near-wall blood flow around
      aortic branches.
AB  - The changes that occur with age in the distribution of atherosclerotic lesions
      around arterial branch points challenge accepted theories relating disease to
      haemodynamic stresses. We investigated whether flow near branch points changes
      with age in a way that can account for the different lesion distributions. Flow
      around 20 branches from immature and mature aortas was investigated by examining
      the length:width ratio and orientation of endothelial nuclei; these properties
      depend on the magnitude and direction of near-wall flows, respectively. There
      were significant changes in the pattern of nuclear shape with age, consistent
      with a reversal in the pattern of shear around branches. In control regions away
      from branches, there were no such changes. The role of haemodynamic stresses in
      atherogenesis may require re-evaluation in the light of these results.

PMID- 14709361
TI  - HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new
      implications for atherosclerosis.
AB  - The beneficial effects of statins in atherosclerosis have been partly attributed
      to their immunomodulating functions. Dendritic cells (DC), which are
      "professional" antigen-presenting cells, were recently detected in
      atherosclerotic plaques. It is assumed that DC play a critical role in the
      immunological processes related to atherosclerosis. Thus, we investigated the
      effects of statins on maturation and antigen-presenting function of DC. Human
      monocyte-derived DC were incubated with simvastatin or atorvastatin (1-10microM)
      for different periods (1-48h), and were subsequently stimulated with a cytokine
      cocktail (1.25ng/ml TNF-alpha, 1ng/ml Il-1beta, and 0.5microg/ml prostaglandin
      E(2)) to induce maturation. In contrast to untreated DC, statin-preincubated DC
      exhibited an immature phenotype and a significantly lower expression of the
      maturation-associated markers CD83, CD40, CD86, HLA-DR, and CCR7. The inhibitory
      statin effect was completely reversed by mevalonate or geranylgeranyl
      pyrophosphate. In addition, preincubation with statins significantly reduced the
      ability of cytokine-stimulated DC to induce T cell proliferation. In the present
      study, we have shown that statins inhibit the maturation and antigen-presenting
      function of human myeloid dendritic cells, thus maybe contributing to their
      beneficial effects in atherosclerosis. Therefore, the use of statins as
      immunomodulators might also provide a new therapeutic approach to other
      immunological disorders.

PMID- 14709362
TI  - High prevalence of peripheral arterial disease and co-morbidity in 6880 primary
      care patients: cross-sectional study.
AB  - We aimed to obtain reliable data on the epidemiology, co-morbidities and risk
      factor profile of peripheral arterial disease (PAD) in general medical practise.
      In the cross-sectional part of the observational German Epidemiological Trial on
      Ankle Brachial Index (getABI study), 344 general practitioners throughout Germany
      determined the ABI of consecutive, unselected patients aged 65 years or older
      with bilateral Doppler ultrasound measurements. Additional assessments comprised
      patient history with the focus on atherothrombotic diseases, physical
      examination, and the WHO questionnaire on intermittent claudication. A total of
      6880 patients were included (42.0% male, mean age 72.5 years, mean body mass
      index 27.3 kg/m(2), mean systolic/diastolic blood pressure 143.7/81.3 mmHg). The
      prevalence of PAD for men/women as indicated by an ankle brachial index (AB1)<0.9
      was 19.8/16.8%. Patients with PAD were slightly older than patients without PAD,
      suffered more frequently from diabetes (36.6 vs. 22.6%; adjusted OR: 1.8),
      hypertension (78.8 vs. 61.6%; OR: 2.2), lipid disorders (57.2 vs. 50.7%; OR: 1.3)
      and other coexisting atherothrombotic diseases (any cerebrovascular event: 15.0
      vs. 7.6%; OR: 1.8; any cardiovascular event: 28.9 vs. 17.0%; OR: 1.5). The data
      highlight the high prevalence of PAD in primary care. PAD patients are
      characterised by a high co-morbidity, particularly with regard to other
      manifestations of atherothrombosis. Doppler ultrasound measurement for ABI
      determinations is a non-invasive, inexpensive, reliable tool in primary care and
      enables GPs to identify patients at risk of PAD.

PMID- 14709363
TI  - C-reactive protein and microalbuminuria differ in their associations with various
      domains of vascular disease.
AB  - C-reactive protein (CRP) and microalbuminuria (MA) have been identified as risk
      markers for cardiovascular disease (CVD). We questioned whether CRP and MA are
      similar markers of vascular disease in different regions of the vascular tree
      like the heart, kidneys and extremities or if they differ in their relationships
      with these vascular beds. Baseline levels of CRP and urinary albumin were
      measured in 6669 non-diabetic participants in the Prevention of Renal and
      Vascular ENdstage Disease (PREVEND) study, a Dutch cohort derived from the
      general population. We defined three domains of vascular disease; coronary heart
      disease (myocardial infarction or infarct pattern on the ECG), renal
      insufficiency (creatinine clearance <60 ml min(-1)) and peripheral artery disease
      (ankle brachial index <0.9 or lower limb revascularisation). The prevalence of an
      elevated CRP (27.7 vs. 17.9%) and MA (17.5 vs. 10.4%) were increased in subjects
      with vascular disease as compared with subjects without CVD. The prevalence of an
      elevated CRP was equal in subjects with either coronary heart disease, renal
      insufficiency or peripheral artery disease (28.4 vs. 29.5 vs. 26.0%, NS), whereas
      MA was most prevalent in subjects with coronary heart disease (22.5 vs. 12.8 vs.
      14.9%, P<0.05). Using multivariate analyses, CRP was independently associated
      with all three domains of vascular disease, whereas MA was independently
      associated with coronary heart disease only. In addition, we found synergistic
      contributions of an elevated CRP and older age to the risk of vascular disease in
      all three domains. Thus, CRP and MA are risk markers for vascular disease, each
      showing a different risk profiling for different vascular beds.

PMID- 14709364
TI  - Glucose interaction magnifies atherosclerotic risk from cholesterol. Findings
      from the PDAY Study.
AB  - OBJECTIVE: To examine whether the atherosclerotic risk from cholesterol is
      modified by serum glucose level. METHODS: Data from the Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY) study of 1530 individuals with
      complete autopsy data for total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C) and hemoglobin A1c (HbA1c) were examined with any
      atherosclerotic raised lesions (RL) >0% of surface area on any of three arterial
      specimens as the outcome. A TC/HDL-C ratio was categorized into quintiles and
      HbA1c was dichotomized as the upper quartile versus lower three quartiles. Odds
      ratios (ORs) were estimated from logistic regression models adjusting for sex,
      race, age, body mass index, smoking and hypertension. RESULTS: An interaction
      product term of TC/HDL x HbA1c was statistically significant (P=0.006) despite
      adjustment for the main effects and other covariates. In models stratified by
      HbA1c, ORs (3.0, 3.9, 1.9, 3.5) for four upper quintiles of TC/HDL-C in the upper
      HbA1c stratum were substantially higher than those in the lower HbA1c stratum
      (0.9, 1.3, 1.4 and 1.1). Strata differences were even more striking in the subset
      of those > or =25 years old. CONCLUSIONS: These results suggest a synergistic
      interaction between glucose and cholesterol that magnifies the atherosclerotic
      risk associated with TC/HDL-C for those with higher HbA1c levels.

PMID- 14709365
TI  - Clinical and nutritional correlates of C-reactive protein in type 2 diabetic
      nephropathy.
AB  - BACKGROUND: Patients with diabetic nephropathy are at elevated cardiovascular
      risk. C-reactive protein (CRP) has been used to successfully predict
      cardiovascular events. OBJECTIVE: We identified clinical and biochemical
      characteristics that correlate with CRP levels in diabetic nephropathy patients.
      DESIGN: Baseline data obtained from 722 patients in the Irbesartan Diabetic
      Nephropathy Trial included age, sex, body mass index (BMI), systolic blood
      pressure (BP), serum creatinine, plasma low- and high-density cholesterol,
      triacylglycerol, serum albumin, hemoglobin A1C, 24h urinary protein excretion,
      plasma total homocysteine (tHcy), folate, B12, pyridoxal 5'-phosphate (PLP,
      active form of Vitamin B(6)), and plasma CRP levels. RESULTS: In univariate
      analyses CRP was positively associated with female sex (r=0.08; P=0.04), BMI
      (r=0.34; P<0.01), serum creatinine (r=0.21; P<0.01), hemoglobin A1C (r=0.08;
      0.04), and inversely associated with PLP (r=-0.17; P<0.01) and folate (r=-0.09;
      P=0.02). A stepwise multiple regression model found CRP directly correlated with
      BMI (P<0.01) and serum creatinine (P<0.01), and inversely correlated with PLP
      (P<0.01). The final model explained 16% of the total variance of CRP.
      CONCLUSIONS: These results extend previous findings of an inverse relationship
      between Vitamin B(6) and CRP. The lack of association between CRP and certain
      established or emerging cardiovascular risk factors offers novel information
      regarding cardiovascular risk in this population.

PMID- 14709366
TI  - Effects of long-term negative energy balance with exercise on plasma lipid and
      lipoprotein levels in identical twins.
AB  - Plasma lipid and lipoprotein concentrations were measured before and after a
      58,000kcal (244MJ) negative energy balance protocol induced entirely by
      supervised endurance exercise over a 93-day period in seven pairs of young
      sedentary and healthy male monozygotic twins. The negative energy balance induced
      significant changes in all measures of body weight and composition except fat
      free mass. The mean weight loss was 5.0+/-0.6kg, and it was entirely accounted
      for by the loss of body fat. In response to the program, improvement in the
      plasma lipid profile was seen including decreases in plasma total (P=0.028) and
      low density lipoprotein (LDL) (P=0.004) cholesterol; total cholesterol/high
      density lipoprotein (HDL) cholesterol ratio (P=0.002); and HDL apolipoprotein A-I
      concentration (P=0.062). Statistically significant within-pair resemblance was
      found for the changes in total and very low density lipoprotein (VLDL)
      cholesterol; total, VLDL and LDL triglycerides, and total, VLDL and LDL
      apolipoprotein B. The findings suggest that favorable changes in the lipid
      profile can be obtained through chronic negative energy balance achieved by
      clamping daily energy intake and adding daily moderate intensity exercise even in
      persons with relatively normal lipid levels at baseline. Furthermore, within-pair
      resemblance among twin brothers strongly suggests that genetic differences
      partially account for the variation in the response of lipids and lipoproteins to
      the negative energy balance protocol.

PMID- 14709367
TI  - The interactive effects of hepatic lipase gene promoter polymorphisms with sex
      and obesity on high-density-lipoprotein cholesterol levels in Taiwanese-Chinese.
AB  - OBJECTIVES: Hepatic lipase (HL) is involved in the metabolism of several
      lipoproteins and plays a key role in reverse cholesterol transport. The aim of
      the current study was to test the statistical association between two HL gene
      promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a
      Taiwanese-Chinese population. METHODS: A sample population of 716 Taiwanese
      Chinese individuals was analyzed. DNA was extracted from the blood and genotypes
      were determined by polymerase chain reaction, restriction enzyme digestion, and
      agarose gel electrophoresis. RESULTS: Analysis of the data revealed that these
      two polymorphisms are in strong linkage disequilibrium (D/D(max)=0.97, P<0.001).
      A significantly lower total cholesterol/HDL-C ratio was noted for carriers with
      the -514T and -250A alleles compared to non-carriers (P=0.007 and 0.004,
      respectively). A significant trend of the association was also found on the high
      levels of high-density-lipoprotein cholesterol (HDL-C) among carriers with the 
      514T and -250A alleles as opposed to that of non-carriers (P=0.030 and 0.023,
      respectively). Multivariate analysis has demonstrated that the effects of HL
      514C/T and HL-250G/A polymorphisms on HDL-C levels were not affected by subjects'
      sex, body mass index, plasma triglyceride levels and the cholesterol ester
      transfer protein gene TaqIB polymorphism. Subgroup analysis on each sex has
      revealed that the two studied polymorphisms were significantly associated with
      HDL-C levels among males but not significant in women. The same association
      between obese and non-obese men was not consistent. The P-value of the respective
      polymorphisms on HDL-C levels were 0.012 and 0.002 among obese men, but not
      significant among non-obese men. CONCLUSION: Analysis of our data revealed an
      independent association between the HL gene promoter polymorphisms and HDL-C
      levels in Taiwanese-Chinese. The data also suggests that the HL-514C/T and HL
      250G/A polymorphisms interact with sex and obesity on HDL-C levels. The findings
      give clues for identifying high risk population in preventive medicine and
      clinical diagnosis. The subsequent impacts on treatment profiles and prognosis
      were derived from this study.

PMID- 14709368
TI  - Smoking and diabetes differ in their associations with subclinical
      atherosclerosis and coronary heart disease-the ARIC Study.
AB  - Atherosclerosis, nearly universally present in major arteries of Western adults,
      is characterized in all affected arteries by cholesterol-laden plaques and
      consistently associated with blood cholesterol levels. Other risk factors are
      reported to have relatively stronger or weaker associations with different
      atherosclerotic manifestations, but such differences have never previously been
      quantified. Measuring them may offer fresh clues to atherogenic processes and
      their prevention. The Atherosclerosis Risk in Communities Study (ARIC)
      ascertained incident coronary heart disease (CHD) and measured subclinical
      atherosclerosis as carotid artery intimal medial thickness using ultrasound and
      as lower extremity arterial disease (LEAD) using ankle-brachial blood pressure
      index. Blood cholesterol was associated with all endpoints. When standardized
      against LDL cholesterol associations, diabetes and smoking showed substantially
      different strengths of associations with different endpoints. Relative to
      associations with LDL cholesterol: (1) smoking, but not diabetes, increased in
      its strength of association with the severity of the underlying arterial disease;
      (2) the diabetes and smoking associations with CHD were much stronger in women
      than men, a phenomenon which, the standardization pattern suggests, is due to a
      gender difference in CHD pathogenesis, possibly attributable to arteriolar
      differences.

PMID- 14709369
TI  - The close relationship between postprandial remnant metabolism and insulin
      resistance.
AB  - The aim of this study was to investigate the relationship between postprandial
      remnant-like particle (RLP) metabolism and insulin resistance (IR). The study
      group consisted of 52 randomly selected subjects. To evaluate postprandial
      hyperlipidemia, serum lipid and lipoprotein concentrations during fasting and 4h
      after the fat-loading test were measured in each subject. IR was assessed using
      the index of homeostasis model assessment (HOMA-R). The subjects were divided
      into two groups according to the value of HOMA-R: an IR group (n=17) with a HOMA
      R value >/=1.73, and a normal (NR) group (n=35) with a HOMA-R value <1.73. Both
      fasting and postprandial RLP-cholesterol (RLP-C) concentrations were higher in
      the IR group than in the NR group (6.2+/-2.6 versus 4.1+/-1.7mg/dl fasting value,
      and 9.7+/-4.0 versus 5.8+/-2.9mg/dl postprandial value). The changes in RLP-C
      concentration during the fat-loading test were twice as high in the IR group
      compared with the NR group (3.5+/-2.4 versus 1.6+/-1.6mg/dl, P=0.0022). The HOMA
      R correlated significantly with both fasting and postprandial triglyceride
      (r=0.41 and 0.43, respectively) and RLP-C (r=0.36 and 0.50, respectively) in all
      subjects. Multiple regression analysis indicate that postprandial RLP-C
      concentration was an independent predictor of HOMA-R regardless of age, BMI, and
      other lipid profiles. Thus, postprandial RLP metabolism is closely related to IR.
      Atherosclerotic proliferation in IR syndrome may be caused by the accumulation of
      postprandial remnant lipoproteins after the daily fat intake.

PMID- 14709370
TI  - Response of lipoprotein(a) levels to therapeutic life-style change in obese
      African-Americans.
AB  - Lipoprotein(a) (Lp(a)) is regarded as an independent risk factor for
      Atherosclerotic cardiovascular disease. The objectives of this study were: to
      determine the effects of diet and exercise on Lp(a) and to evaluate the relation
      of Lp(a) with the lipid profile (total serum cholesterol (TC), triglycerides
      (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL)
      cholesterol). Baseline Lp(a), body mass index (BMI) and the lipid profiles were
      measured in 343 Obese (BMI >30kg/m(2)) African-Americans. After a 3-month
      intervention of diet and exercise by 105 participants, their lipids were re
      measured. Baseline Lp(a) levels ranged from 1.2 to 280mg/dl. Lp(a) was inversely
      associated with triglyceride (P<0.05). After the intervention, Lp(a) and HDL
      increased by a mean of 20 and 5%, respectively. Total cholesterol, triglycerides,
      LDL and BMI decreased by 7, 10, 11 and 8%, respectively. Women taking estrogen
      replacement had a negligible change in Lp(a) while participants taking HMG-CoA
      reductase inhibitors had an increase in Lp(a) levels by 30%.

PMID- 14709371
TI  - Urinary cyclic GMP excretion and blood pressure levels in a general population.
AB  - Dysfunction of the nitric oxide (NO) system is potentially involved in the
      development of hypertension, but only limited data are currently available from
      experimental or clinical studies. We investigated cross-sectionally the relation
      between urinary excretion of cyclic guanosine 3',5'-monophosphate (cyclic GMP), a
      second messenger of NO, and hypertension in a general population sample of
      Japanese men and women. The samples comprised 1541 subjects (788 men and 753
      women) aged 40-79 years who participated in cardiovascular risk surveys between
      1997 and 2002 and underwent a 24h urine collection. Urinary excretion of cyclic
      GMP was measured using a 125I-labeled cyclic GMP radioimmunoassay, and was
      adjusted for urinary creatinine excretion (nmol/mmol creatinine). Urinary cyclic
      GMP excretion was 66.0+/-62.0nmol/mmol creatinine (mean+/-S.D.). Compared with
      normal blood pressure individuals, the multivariate-adjusted mean value of
      urinary cyclic GMP excretion was significantly higher in people with moderate
      hypertension, but not higher in severe hypertension. Among subjects with
      hypertensive end-organ damage, we observed reduced urinary cyclic GMP excretion
      in severe hypertension and no increased excretion in moderate hypertension,
      compared with normal blood pressure. Although we had the limited number of
      subjects with severe hypertension (n=15), our data suggest that NO bioactivity
      may be increase in the early stage of hypertension but decreased in severe
      hypertension with end-organ damage.

PMID- 14709372
TI  - Association of gene polymorphisms with coronary artery disease in individuals
      with or without nonfamilial hypercholesterolemia.
AB  - A substantial proportion of individuals with coronary artery disease (CAD) has
      concomitant hypercholesterolemia. A large-scale association study was performed
      to identify separately genes that confer susceptibility to CAD in the absence or
      presence of nonfamilial hypercholesterolemia. The study population comprised 5248
      unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735
      women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541
      individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707
      individuals (1991 men, 716 women) did not have this condition. The genotypes for
      33 polymorphisms of 27 candidate genes were determined with a fluorescence- or
      colorimetry-based allele-specific DNA primer-probe assay system. Multivariate
      logistic regression analysis with adjustment for age, body mass index, and the
      prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia
      revealed that three polymorphisms [994G --> T (Val279Phe) in the platelet
      activating factor acetylhydrolase gene, 242C --> T (His72Tyr) in the NADH/NADPH
      oxidase p22 phox gene, and 1100C --> T in the apolipoprotein C-III gene] were
      significantly associated with CAD in men with hypercholesterolemia. Genotyping of
      these three polymorphisms may prove informative for prediction of the genetic
      risk for CAD in men with nonfamilial hypercholesterolemia.

PMID- 14709373
TI  - Soluble thrombomodulin and vascular adhesion molecule-1 are associated to leptin
      plasma levels in obese women.
AB  - Recent studies have suggested that leptin, a plasma protein secreted by
      adipocytes, may play a role in artherothrombosis. In this study, we tested the
      hypothesis that leptin contributes to in vivo endothelial dysfunction in obese
      subjects. A cross-sectional comparison of plasma leptin, soluble thrombomodulin
      (sTM) and soluble vascular adhesion molecule-1 (VCAM-1) was carried out in 35
      obese women (age 48+/-13) selected with a body mass index (BMI) > or =30kg/m(2)
      and 25 normal weight women (age 50+/-11, BMI < 25). An additional study was
      conducted to determine the short-term effects of weight loss induced by caloric
      restriction. Plasma levels of leptin, sTM and sVCAM-1 were measured before and
      after weight loss. Obese women had higher levels of leptin (35+/-22 versus 22+/
      19, P<0.01), sTM (4.8+/-1.8 versus 1.9+/-1.5, P<0.001) and sVCAM-1 (726+/-109
      versus 583+/-50, P<0.001) than non-obese women. sTM and sVCAM-1 concentrations
      had a positive correlation with BMI (sTM, r=0.70, P<0.001; sVCAM-1, r=0.60,
      P<0.001), waist circumference (sTM, r=0.66, P<0.001; sVCAM-1, r=0.37, P<0.01) and
      leptin levels (sTM, r=0.53, P<0.001; sVCAM-1, r=0.42, P<0.005). At multiple
      regression analysis leptin predicted sTM and sVCAM-1 independently of obesity
      measures and other covariates. Twenty-nine obese patients who completed the
      program of weight reduction showed a significant decrease in leptin, sTM, and
      sVCAM-1 levels. The magnitude of decrease of sTM and sVCAM-1 was related to the
      magnitude of reduction in leptin levels. Therefore, our results show that obesity
      is associated with enhanced levels of atherosclerosis markers. These
      abnormalities are related to abdominal obesity possibly mediated by leptin
      levels, and are reversible with weight loss.

PMID- 14709374
TI  - Increased circulating malondialdehyde-modified LDL in the patients with familial
      combined hyperlipidemia and its relation with the hepatic lipase activity.
AB  - Familial combined hyperlipidemia (FCHL) is characterized by elevated levels of
      serum total cholesterol (TC), triglyceride (TG), or both. The increased incidence
      of coronary artery diseases (CAD) in the patients with FCHL is believed to be
      caused by circulating atherogenic lipoproteins associated with the complex
      phenotype. Recent establishment of sensitive detection system for malondialdehyde
      modified (MDA)-LDL, which is one of oxidized lipoproteins, showed its increased
      circulating level in the patients with CAD. In order to know the atherogenic
      lipoproteins resulted from the dyslipidemia observed in FCHL, we measured the
      serum MDA-LDL level in the patients. The circulating MDA-LDL level and the ratio
      of MDA-LDL and LDL-C in FCHL were significantly higher (P<0.05) than those in
      control, which are adjusted about the age, serum TC, LDL-C and HDL-C levels,
      respectively. Furthermore, the circulating MDA-LDL level and the ratio of MDA-LDL
      and LDL-C were negatively correlated (R=-0.635, P<0.01 and R=-0.702, P<0.01,
      respectively) with hepatic lipase (HL) activity in FCHL. The serum MDA-LDL level
      and the ratio of MDA-LDL and LDL-C were in the subjects with T/T genotypes in the
      HL C-514T polymorphism were significantly increased compared to those with C/C
      genotype, respectively. The subjects with T/T genotype showed the activities to
      65 and 79% of those in the subjects with C/C genotype in male and female,
      respectively. The intima-media thickness (IMT) of carotid artery was
      significantly higher (P<0.05) in the subjects with T/T genotype than those with
      C/C genotype in male. These findings indicate that the circulating MDA-LDL level
      is possibly contributing the atherogenic process in FCHL, and the common HL
      polymorphism might be a determinant of the serum level of oxidized LDL in the
      patients with FCHL.

PMID- 14709375
TI  - Adventitial heat shock protein 60 in human coronary atherosclerosis.

PMID- 14709376
TI  - Lipid-lowering drugs and homocysteine. A comparison between statins and other
      lipid-lowering drugs.

PMID- 14709377
TI  - Relationship of post-heparin hepatic and lipoprotein lipases to high density
      lipoprotein modulation in obese children.

PMID- 14709378
TI  - Association analysis between polymorphisms of the lymphotoxin-alpha gene and
      myocardial infarction in a Japanese population.

PMID- 14709379
TI  - Hyperhomocysteinemia due to Helicobacter pylori?

PMID- 14709380
TI  - Simultaneous multi-analyte determination of estrone, isoproturon and atrazine in
      natural waters by the RIver ANAlyser (RIANA), an optical immunosensor.
AB  - In most medical and environmental applications of biosensors, only single
      analytes are determined. However, the monitoring of several analytes is obviously
      preferable in order to gather more information about the sample under analysis.
      In line with this, different technologies are being developed to obtain multi
      analyte sensors. In this paper, an analytical method for the simultaneous
      determination of three different contaminants-atrazine, isoproturon, and estrone
      in natural waters by using an optical immunosensor prototype, the so-called
      "RIver ANAlyser" (RIANA), is described. RIANA is based on a rapid solid-phase
      fluoroimmunoassay that takes place at an optical transducer chip. The transducer
      surface is chemically modified with three analytes derivatives placed in
      different discrete locations. The sensor surface can be regenerated thus allowing
      the performance of several measurements with the same transducer. Each test
      cycle, including one regeneration step, is accomplished in 15 min. Detection
      limits achieved were 0.155, 0.046, and 0.084 microg/l, for atrazine, isoproturon,
      and estrone, respectively. Satisfactory repetition, with relative standard
      deviations between 1.06 and 6.98%, was obtained. Excluding a minor non-specifical
      binding of the isoproturon antibodies, no cross-reactivity effects were observed.
      Matrix effects were significant only in the case of wastewater samples. Biosensor
      measurements were validated using conventional liquid chromatography-mass
      spectrometry. The results obtained with both techniques were in good agreement.

PMID- 14709381
TI  - Biosensors for determination of total and natural antioxidant capacity of red and
      white wines: comparison with other spectrophotometric and fluorimetric methods.
AB  - Research was carried out to experimentally evaluate the antioxidant capacity of
      several red and white wines using a superoxide dismutase (SOD) biosensor recently
      developed by the present authors. Measurements were performed by comparing the
      biosensor response to increasing concentration of the superoxide radical produced
      in solution by the xanthine/xanthine oxidase system, both in the presence and
      absence of the test sample.The results were compared with those of two
      traditional spectrophotometric methods and of a spectrofluorimetric method
      described in literature.Lastly, also the polyphenol, sulfite and ascorbic acid
      contents of the different wine samples examined were measured using a tyrosinase
      biosensor, a sulfite oxidase biosensor and an ascorbate oxidase biosensor,
      respectively.

PMID- 14709382
TI  - Direct detection of glucose by surface plasmon resonance with bacterial
      glucose/galactose-binding protein.
AB  - The monitoring and management of blood glucose levels are key components for
      maintaining the health of people with diabetes. Traditionally, glucose monitoring
      has been based on indirect detection using electrochemistry and enzymes such as
      glucose oxidase or glucose dehydrogenase. Here, we demonstrate direct detection
      of glucose using a surface plasmon resonance (SPR) biosensor. By site
      specifically and covalently attaching a known receptor for glucose, the
      glucose/galactose-binding protein (GGBP), to the SPR surface, we were able to
      detect glucose binding and determine equilibrium binding constants. The site
      specific coupling was accomplished by mutation of single amino acids on GGBP to
      cysteine and subsequent thiol conjugation. The resulting SPR surfaces had glucose
      specific binding properties consistent with known properties of GGBP. Further
      modifications were introduced to weaken GGBP-binding affinity to more closely
      match physiologically relevant glucose concentrations (1-30 mM). One protein with
      a response close to this glucose range was identified, the GGBP triple mutant
      E149C, A213S, L238S with an equilibrium dissociation constant of 0.5mM. These
      results suggest that biosensors for direct glucose detection based on SPR or
      similar refractive detection methods, if miniaturized, have the potential for
      development as continuous glucose monitoring devices.

PMID- 14709383
TI  - Determination of binary pesticide mixtures by an acetylcholinesterase-choline
      oxidase biosensor.
AB  - In this study, acetylcholinesterase (AChE) and choline oxidase (ChO) were co
      immobilized on poly(2-hydroxyethyl methacrylate) (pHEMA) membranes to construct a
      biosensor for the detection of anti-cholinesterase compounds. pHEMA membranes
      were prepared with the addition of SnCl(4) to achieve the desired porosity.
      Immobilization of the enzymes was done by surface attachment via epichlorohydrin
      (Epi) and Cibacron Blue F3G-A (CB) activation. Enzyme immobilized membrane was
      used in the detection of anti-cholinesterase activity of aldicarb (AS),
      carbofuran (CF) and carbaryl (CL), as well as two mixtures, (AS+CF) and (AS+CL).
      The total anti-cholinesterase activity of binary pesticide mixtures was found to
      be lower than the sum of the individual inhibition values.

PMID- 14709384
TI  - Development of a direct-binding chloramphenicol sensor based on thiol or sulfide
      mediated self-assembled antibody monolayers.
AB  - A batch-type antibody-immobilized quartz crystal microbalance (QCM) system for
      detecting chloramphenicol (CAP) was developed. To bind an anti-CAP antibody onto
      the gold electrode surface of piezoelectric crystals, self-assembled monolayers
      (SAMs) of different thiols or sulfides were formed by a chemisorption procedure.
      Then, the anti-CAP antibody was covalently linked to the pre-formed monolayers by
      an activation procedure using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
      hydrochloride and N-hydroxysulfosuccinimide. The antibody-immobilized QCM chip
      thus prepared was installed in a well holder and was measured for sensor
      response. Compared with the bare QCM chip and the QCM chip only coated with 3
      mercaptopropionic acid (MPA), the antibody-immobilized sensor showed greatly
      enhanced frequency shifts by 10-50-fold after CAP injection. In this case, CAP
      detection which was indicated by steady-state resonant frequency shift was
      accomplished within 10 min. When CAP solution was injected into the reaction cell
      in 50mM concentration, the frequency shifts obtained were, respectively, 530 and
      505 Hz in case of thiosalicylic acid and MPA immobilization. Repeated use of the
      sensor chips up to eight times was possible after 1 min regeneration with 0.1M
      NaOH. This system demonstrated a potential application of thiol or sulfide
      mediated SAMs as the pre-coatings of a real-time detection on CAP in solution.

PMID- 14709386
TI  - A visual DNA chip for simultaneous detection of hepatitis B virus, hepatitis C
      virus and human immunodeficiency virus type-1.
AB  - For the simultaneously visual detection of hepatitis B virus (HBV), hepatitis C
      virus (HCV) and human immunodeficiency virus type-1 (HIV-1), a qualitative DNA
      chip method, combining multiplex and nested polymerase chain reaction (PCR) with
      arrayed anchored primer PCR and a biotin-avidin alkaline phosphatase (Av-AP)
      indicator system, was developed. After pretreatment of infected blood samples and
      reverse transcription of the RNA virus genome, PCR was performed in a single tube
      by using the outer primer pairs. Second round nested multiplex PCR was performed
      on the DNA chip, on which the primers array had already been prepared. During the
      arrayed anchored multiplex PCR, 5[N-(N-biotinylaminocaproyl)-epsilon-3
      aminoallyl]-2-deoxy-uridine-5-triphosphate (biotin-11-dUTP) was incorporated into
      the extended DNA chains in order to bind avidin alkaline phosphatase via avidin
      and biotin. To produce purple precipitates on the chips, the enzyme substrate 5
      bromo-4-chloro-3-indolyl phosphate (BCIP) was used in conjunction with the
      enhancer, nitro blue tetrazolium (NBT). Blood samples containing the three
      viruses were tested using this DNA chip and about 1 pg of specific viral DNA
      fragments were detected on the chip wells after nested PCR.

PMID- 14709385
TI  - Measuring synchronization in neuronal networks for biosensor applications.
AB  - Cultures of neurons can be grown on microelectrode arrays (MEAs), so that their
      spike and burst activity can be monitored. These activity patterns are quite
      sensitive to changes in the environment, such as chemical exposure, and hence the
      cultures can be used as biosensors. One key issue in analyzing the data from
      neuronal networks is how to quantify the level of synchronization among different
      units, which represent different neurons in the network. In this paper, we
      propose a synchronization metric, based on the statistical distribution of unit
      to-unit correlation coefficients. We show that this synchronization metric
      changes significantly when the networks are exposed to bicuculline, strychnine,
      or 2,3-dioxo-6-nitro-l,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamide (NBQX).
      For that reason, this metric can be used to characterize pharmacologically
      induced changes in a network, either for research or for biosensor applications.

PMID- 14709387
TI  - Novel amperometric immunosensors based on iridium oxide matrices.
AB  - Novel immunosensors based on antibodies immobilized in electrochemically grown
      iridium oxide (IrOx) thin film matrices have been developed. Antibody loading in
      the oxide was evaluated using a non-competitive electrochemical immunoassay for
      IgG. Anti-IgG loading in the oxide was found to be dependent on the concentration
      of anti-IgG present in the oxide growth step, with 400 microg/ml anti-IgG
      producing maximum amperometric responses. To study the potential analytical
      properties of the matrix, the dose-response behavior of the sensors was
      determined using optimized alkaline phosphatase-linked IgG immunoassay.
      Hydroquinone diphosphate (HQDP) was used as enzyme substrate and the oxidation of
      hydroquinone was detected amperometrically at +420 mV. The sensors displayed a
      linear dose-response behavior for IgG concentrations between 10 and 200 ng/ml,
      saturating above 600 ng/ml, and had a low detection limit of 8 ng/ml.Finally, the
      method was used to produce sensors containing immobilized anti-transferrin. Using
      a non-optimized electrochemical immunoassay for human transferrin (HT), dose
      response behavior was observed for HT concentrations between 100 and 600
      ng/ml.The results presented in this paper show that IrOx matrices represent a new
      method for immunosensor fabrication. The oxide acts as a hydrophilic, highly
      porous, three-dimensional matrix that can immobilize antibodies and retain their
      activity. The method is attractive because it offers the potential for high
      antibody loadings and is suitable for mass production of sensors in an easy and
      economical manner.

PMID- 14709388
TI  - A piezoelectric immunoagglutination assay for Toxoplasma gondii antibodies using
      gold nanoparticles.
AB  - The serologic detection of anti-Toxoplasma gondii immunoglobulins plays a key
      role in the clinical diagnosis of Toxoplasmosis. In this paper, a simple, rapid
      and highly sensitive agglutination-based piezoelectric immunoassay has been
      firstly developed for directly detecting anti-T. gondii immunoglobulins in
      infected rabbit serum (IRS) and infected rabbit blood (IRB). The proposed
      technique is based on that the specific agglutination of antigen-coated gold
      nanoparticles, averaging 10nm in diameter, in the presence of the corresponding
      antibody causes a frequency change that is monitored by a piezoelectric device.
      In contrast to the commonly used piezoelectric assays, it possesses an attractive
      advantage in that the immobilization of antibody or antigen on the crystal is
      unnecessary. Use of a newly prepared sensing probe which was modified by a plasma
      polymerized film (PPF) of n-butyl amine and further by a heparin layer resulted
      in a response-enhanced immunoagglutination and a high compatibility of the probe
      with biological samples. An appropriate reagent consisting of 1% normal rabbit
      serum (NRS) and 0.1% bovine serum albumin (BSA) for diluting the analytes were
      verified in counteracting the background interference of assay. Moreover, an
      optimization of assay medium composition with the addition of poly(ethylene
      glycol) (PEG) serving as immunoagglutination rate and sensitivity enhancer was
      investigated in detail. It is found that the developed immunoagglutination assay
      system is sensitive to dilution ratio of anti-T. gondii antibody as low as
      1:5500. Analytical results of several specimens obtained using the developed
      technique are in satisfactory agreement with those given by the ELISA method,
      implying a promising alternative approach for detecting anti-T. gondii antibodies
      in the clinical diagnosis.

PMID- 14709389
TI  - A novel piezoelectric quartz micro-array immunosensor based on self-assembled
      monolayer for determination of human chorionic gonadotropin.
AB  - A novel multi-channel 2 x 5 model of piezoelectric quartz micro-array
      immunosensor has been developed for quantitative detection of human chorionic
      gonadotropin (hCG) in serum or urine samples. Every crystal unit of the
      fabricated piezoelectric hCG micro-array immunosensor can oscillate independently
      without interfering each other. A 2 x 5 model of micro-array immunosensor as
      compared with a one-channel immunosensor can provide eight times higher detection
      speeds for hCG assay. The anti-hCG antibody is deposited on the gold electrode's
      surface of 10 MHz quartz AT-cut crystal by self-assembled technique using
      sulfosuccinimidyl 6-[3'-(2-pyridyldithio) propionamido] hexanoate (Sulfo-LC
      SPDP), and serves as an antibody recognizing layer. The highly ordered self
      assembled monolayers (SAM) ensure well-controlled surface structure and offer
      many advantages to the performance of the sensor. Compared with conventional
      antibody immobilization methods, the amount and the reaction activity of antibody
      monolayer coated by the SAM binding are bigger than those by the SPA method, and
      less non-specific binding caused by other analytes in sample is found. Under the
      optimized experimental conditions, the results showed that micro-array
      immunosensor quantitatively detected serum or urine hCG in the range of 2.5-500
      mIU/ml with high precision (CV<5%); other hormones in human serum and urine did
      not interfere with the determination markedly. Serum and urine samples of 60
      patients were detected by the micro-array immunosensor, and the results agreed
      well with those given by the commercial radioimmunoassay test kit, with
      correlation coefficient of 0.92. After regeneration with urea solution the coated
      immunosensor can be reused five times without appreciable loss of activity.

PMID- 14709390
TI  - A biosensor for the analysis of acetonitrile.
AB  - A biosensor for monitoring acetonitrile was constructed. A mixed culture was
      taken from a degradation reactor and mounted on top of a Clark electrode. The
      amperometric biosensor was placed in a flow-through cell and integrated into a
      flow injection system. The metabolic response in terms of oxygen consumption was
      well correlated to the concentration of acetonitrile in standard solutions.
      However, when the reaction products, acetic acid and ammonia, were also present,
      the response was erratic, due to the additional metabolic reaction on acetate. By
      introducing a hydrophobic barrier it was possible to eliminate the negative
      influence of these charged products and thus to improve the operational
      selectivity of the sensor. The biosensor showed good stability for analysis
      during at least 6 days and future work will focus on using it for monitoring and
      control of degradation processes.

PMID- 14709391
TI  - Target discrimination by surface-immobilized molecular beacons designed to detect
      Francisella tularensis.
AB  - A molecular beacon (MB) array was designed based on unique regions of the 16S
      rRNA of the bacterium Francisella tularensis. Nucleic acid molecular beacons
      undergo a spontaneous fluorogenic conformational change when they hybridize to
      specific complementary targets. The array was printed on aldehyde glass or
      hydrogel slides and evaluated for functioning in presence of complementary
      oligonucleotide sequences, single-nucleotide mismatch sequences and multiple
      nucleotide mismatch sequences. Discriminating true target from mismatched targets
      was found to be dependent on type, number, and location of mismatches within the
      beacon (i.e. located in the stem or loop regions). Optimal conditions for
      molecular beacon deposition, and target hybridization were determined for
      oligonucleotide target mismatch discrimination. The beacon array was stable upon
      recharging by exposure to an alkaline solution, and repeatedly used. In addition,
      performance of the beacon array biosensor was compared with molecular beacons in
      homogeneous solution.

PMID- 14709392
TI  - A fluorescent coagulation assay for thrombin using a fibre optic evanescent wave
      sensor.
AB  - A fibre optic evanescent wave sensor is used for the rapid detection of thrombin.
      Coagulation of solution phase fluorescently labelled fibrinogen to unlabelled
      fibrinogen bound to the surface of the fibre optic is observed in real time by
      the evanescent wave sensor. Thrombin concentrations down to 0.01 NIHml(-1) are
      detectable within 5 min. The potential application of this technique for rapid
      amplified immunosensing is discussed.

PMID- 14709393
TI  - Application of on-chip cell cultures for the detection of allergic response.
AB  - In this report, the development of a microfluidic cell chip for monitoring
      allergic response is described. A rat basophilic leukemia cell line (RBL-2H3), a
      tumor analog of rat mucosal mast cells, has been used as a model to observe its
      allergic response upon antigen stimulus. The cells were cultivated on a
      poly(dimethylsiloxane) (PDMS) chip, the surface of which was modified by several
      methods. The PDMS chip, which comprised a cell cultivation chamber and
      microfluidic channels, was fabricated by conventional molding methods. In order
      to detect the allergic response, a fluorescent dye, quinacrine, was introduced
      inside the cell compartment that included histamine. The cells were stimulated
      with dinitrophenylated bovine serum albumin (DNP-BSA) after incubation with anti
      DNP IgE. When exocytosis events occurred, the microfluidic system detected the
      fluorescent signal of quinacrine, which was released from RBL-2H3 cells by using
      a photomultiplier tube (PMT) fitted onto a microscope.

PMID- 14709394
TI  - A low noise multichannel integrated circuit for recording neuronal signals using
      microelectrode arrays.
AB  - This paper reports on the development of a fully integrated 32-channel integrated
      circuit (IC) for recording neuronal signals in neurophysiological experiments
      using microelectrode arrays. The IC consists of 32 channels of low-noise
      preamplifiers and bandpass filters, and an output analog multiplexer. The
      continuous-time RC active filters have a typical passband of 20-2000 Hz; the low
      and the high cut-off frequencies can be separately controlled by external
      reference currents. This chip provides a satisfactory signal-to-noise ratio for
      neuronal signals with amplitudes greater than 50 microV. For the nominal passband
      setting, an equivalent input noise of 3 microV rms has been achieved. A single
      channel occupies 0.35 mm(2) of silicon area and dissipates 1.7 mW of power. The
      chip was fabricated in a 0.7 microm CMOS process.

PMID- 14709395
TI  - Transition metal half-sandwich complexes as redox mediators to glucose oxidase.
AB  - Chromium and manganese half-sandwich complexes are evaluated as mediators to
      glucose oxidase (GOx) since they are of similar size to ferrocene derivatives
      (sandwich complexes) and contain a single pi-ligand for interaction with the
      enzyme co-factor. A series of seven amino derivatives of [(eta
      C(6)H(6))Cr(CO)(3)] were investigated of which only [[eta
      C(6)Me(4)(NH(2))(2)]Cr(CO)(3)] (7), with the lowest oxidation potential of +40 mV
      (versus SCE), was found to display reversible electrochemistry. Small catalytic
      currents were recorded in the presence of GOx and glucose when complex (7) was
      incorporated in a screen-printed carbon electrode. Manganese cyclopentadienyl
      (Cp) half-sandwich complexes were found to be more effective GOx mediators and
      comparable in efficacy to ferrocene derivatives. A mediator rate constant k(M) of
      2.1 x 10(5)M(-1)s(-1) was determined for the water-soluble complex [(eta
      MeC(5)H(4))Mn(NO)(CN)(2)]Na (11) compared to a range of 3 x 10(4) to 8 x 10(6)M(
      1)s(-1) previously determined for ferrocenes under the same experimental
      conditions. beta-Cyclodextrin (beta-cd) was found to be helpful in solubilising
      hydrophobic complexes such as [(eta-MeC(5)H(4))Mn(NO)(S(2)CNMe(2))] (15) and the
      neutral oxidised form of [MeCpMn(NO)[(SCCN)(2)]]NEt(4) (14), either directly as
      an inclusion adduct or in situ during cyclic voltammetry. Screen-printed
      amperometric electrodes, containing a mediator and GOx immobilised in an organic
      conducting carbon layer, were useful in assessing the mediation ability of
      complex (15) where aqueous insolubility precluded any kinetic studies with GOx in
      solution. This work was briefly extended to other oxidoreductase enzymes apart
      from GOx. Thus, rotating ring-disk voltammetry demonstrated that the beta-cd
      complex of compound (15) is also a useful mediator to Horseradish peroxidase
      (HRP) since it displays an identical catalytic current to the ferrocene
      ethanolamine derivative (1) used in the MediSense ExacTech and Precision QID
      blood glucose biosensor electrodes.

PMID- 14709396
TI  - Dielectrophoretic registration of living cells to a microelectrode array.
AB  - We present a novel microfabricated device to simultaneously and actively trap
      thousands of single mammalian cells in alignment with a planar microelectrode
      array. Thousands of 3 micromdiameter trapping electrodes were fabricated within
      the bottom of a parallel-plate flow chamber. Cells were trapped on the electrodes
      and held against destabilizing fluid flows by dielectrophoretic forces generated
      in the device. In general, each electrode trapped only one cell. Adhesive regions
      were patterned onto the surface in alignment with the traps such that cells
      adhered to the array surface and remained in alignment with the electrodes. By
      driving the device with different voltages, we showed that trapped cells could be
      killed by stronger electric fields. However, with weaker fields, cells were not
      damaged during trapping, as indicated by the similar morphologies and
      proliferation rates of trapped cells versus controls. As a test of the device, we
      patterned approximately 20000 cells onto a 1cm(2) grid of rectangular adhesive
      regions, with two electrodes and thus two cells per rectangle. Our method
      obtained 70+/-1% fidelity versus 17+/-1% when using an existing cell-registration
      technique. By allowing the placement of desired numbers of cells at specified
      locations, this approach addresses many needs to manipulate and register cells to
      the surfaces of biosensors and other devices with high precision and fidelity.

PMID- 14709397
TI  - Protective actions of gliclazide on high insulin-enhanced neutrophil-endothelial
      cell interactions through inhibition of mitogen activated protein kinase and
      protein kinase C pathways.
AB  - BACKGROUND AND AIM: There are many lines of evidence indicating that
      hyperinsulinemia but not hyperglycemia is linked to the development of
      atherosclerotic diseases such as coronary events in diabetic patients. K(ATP)
      channel blockers of the sulphonylurea class are used widely to treat type 2
      diabetes mellitus even with hyperinsulinemia. In this study, we determined
      whether K(ATP) channel blockers can protect against atherosclerotic processes
      enhanced by hyperinsulinemia, namely leukocyte-endothelial cell interactions. In
      addition, we characterized the intracellular mechanisms involved in protective
      actions of the K(ATP) channel blocker(s). METHOD: Studies of adhesion between
      neutrophils and human umbilical vein endothelial cells incubated in insulin-rich
      medium with or without K(ATP) channel blockers were performed. Adhered
      neutrophils were quantified by measuring their myeloperoxidase activities, and
      surface expression of endothelial ICAM-1 was examined using an enzyme
      immunoassay. RESULTS: Both neutrophil adhesion and ICAM-1 expression enhanced by
      high insulin (100 microU/ml, 48 h) were attenuated by gliclazide (20 microM), but
      not by other K(ATP) channel blockers (glibenclamide, nateglinide, and
      glimepiride). In addition, both neutrophil adhesion and ICAM-1 expression which
      were increased by a MAP kinase activator, anisomycin (1 microM), or a PKC
      activator, phorbol 12-myristate 13-acetate (10 nM) were also attenuated by
      gliclazide. Nitric oxide (NO) synthase inhibitors did not affect these effects of
      gliclazide. CONCLUSIONS: These results suggest that among K(ATP) channel
      blockers, only gliclazide can act directly on endothelial cells to inhibit
      neutrophil-endothelial cell adhesion and ICAM-1 expression enhanced by
      hyperinsulinemia. These effects of gliclazide are mediated through inhibiting
      activation of MAP kinase and PKC, unrelated to NO production.

PMID- 14709398
TI  - Electron microscopic evaluation of the endothelial surface layer of glomerular
      capillaries.
AB  - Recent data from various vascular beds suggest that a layer of
      mucopolysaccharides covering the endothelial cells play an important role in
      transport processes, among others. In this study, electron microscopy (EM) was
      used to explore the presence of an endothelial surface layer (ESL) in rat
      glomerular capillaries. We adopted various fixation and labeling techniques, as
      follows: (1) negatively charged lipid particles were used as a tracer that was
      expected to be excluded from the ESL. The density of intravascular lipid
      particles in flow-arrested capillaries was 89% lower in a 200-nm periendothelial
      area than in the rest of the luminal space (n = 6 rats, P < 0.001); (2) podocytes
      of cryofixed fresh tissue had a 20-nm extramembranous coat, interpreted as the
      true glycocalyx; the coat was less expressed on the endothelium; (3) on unfixed
      endothelial cells, colloidal lanthanum labeled a 60-nm-thick layer, occasionally
      forming lumps; (4) perfusion with a fluorocarbon-based oxygen-carrying fixative,
      followed by tannic acid contrast enhancement, revealed an extensive (> 200 nm)
      ESL not previously described; however, this finding was restricted to superficial
      glomerular capillaries; (5) Cupromeronic Blue cytochemistry displayed a loose
      proteoglycan network in fenestral openings and, occasionally, a semiordered ESL;
      (6) ferricyanide-reduced osmication resulted in increased numbers of fenestral
      diaphragms. In conclusion, this study provides novel morphological evidence to
      support the presence of a significant glomerular ESL.

PMID- 14709399
TI  - Signal transduction pathways activated in human pulmonary endothelial cells by
      OxPAPC, a bioactive component of oxidized lipoproteins.
AB  - The bioactive component of mildly oxidized low-density lipoproteins, oxidized 1
      palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), activates
      tissue factor expression and monocyte adhesion to endothelial cells (EC) from
      systemic circulation, but blocks expression of inflammatory adhesion molecules
      (VCAM, E-selectin) and neutrophil adhesion associated with EC acute inflammatory
      response to bacterial lypopolysacharide (LPS). Due to constant exposure to oxygen
      free radicals, lipids in the injured lung are especially prone to oxidative
      modification and increased OxPAPC generation. In this study, we focused on OxPAPC
      mediated intracellular signaling mechanisms that lead to physiological responses
      in pulmonary endothelial cells. Our results demonstrate that OxPAPC treatment
      activated in a time-dependent fashion protein kinase C (PKC), protein kinase A
      (PKA), Raf/MEK1,2/Erk-1,2 MAP kinase cascade, JNK MAP kinase and transient
      protein tyrosine phosphorylation in human pulmonary artery endothelial cells
      (HPAEC), whereas nonoxidized PAPC was without effect. Pharmacological inhibition
      of PKC and tyrosine kinases blocked activation of Erk-1,2 kinase cascade upstream
      of Raf. OxPAPC did not affect myosin light chain (MLC) phosphorylation, but
      increased phosphorylation of cofillin, a molecular regulator of actin
      polymerization. Finally, OxPAPC induced p60Src-dependent tyrosine phosphorylation
      of focal adhesion proteins paxillin and FAK. Our results suggest a critical
      involvement of PKC and tyrosine phosphorylation in OxPAPC-induced activation of
      Erk-1,2 MAP kinase cascade associated with regulation of specific gene
      expression, and demonstrate rapid phosphorylation of cytoskeletal proteins, which
      indicates OxPAPC-induced EC remodeling.

PMID- 14709400
TI  - Effects of pulmonary ischemia-reperfusion on platelet adhesion in subpleural
      arterioles in rabbits.
AB  - Reperfusion of the ischemic lung is associated with increased pulmonary vascular
      resistance and reduced alveolar perfusion in conjunction with an inflammatory
      response. To determine the contribution of platelet-endothelial interactions, we
      examined effects of pulmonary ischemia-reperfusion (IR) on platelet adhesion and
      diameter of arterioles and investigated the hypothesis that this process is P
      selectin mediated. In anesthetized rabbits with open-chest and ventilated lungs,
      we examined subpleural arterioles by fluorescence microscopy. Ischemia was caused
      by reversibly occluding the right pulmonary artery for 2 h. Fluorescently labeled
      platelets were injected into the right atrium and the right lung was observed
      after 0.5, 1.0, and 2.0 h of reperfusion. Platelets rolling and adherence along
      arterioles occurred with a decrease in diameter that was significant during IR,
      but not after 3- to 5-min occlusion (control). Systemic pretreatment with
      Fucoidan (a ligand to P- and L-selectin) inhibited platelet rolling, adherence,
      and the decrease in diameter. Pretreatment of only exogenously labeled platelets
      with monoclonal antibody (MoAb) to P-selectin prevented platelet rolling and
      adherence, but not the decrease in diameter. These results indicate that in the
      intact lung, pulmonary IR causes platelet rolling and adhesion along arteriolar
      walls, and suggest that this process, which is mediated by P-selectin,
      contributes to vasoconstriction and hypoperfusion. Thus, it appears that platelet
      endothelial interactions may contribute to the development of pulmonary IR
      injury.

PMID- 14709401
TI  - Assessment of hepatic ischemia-reperfusion injury by simultaneous measurement of
      tissue pO2, pCO2, and pH.
AB  - INTRODUCTION: The objective of this study was to determine whether the
      simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple
      parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring
      of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A)
      receptor antagonist (ET(A)-RA) or isotonic saline. METHODS: Fourteen anesthetized
      swine were subjected to 2 h of hepatic vascular exclusion. The animals were
      randomized into two groups: control group (n = 7, saline solution iv) and therapy
      group (n = 7, ET(A)-RA). For evaluation of ischemia-reperfusion injury, the data
      of the multiple-parameter sensor (pO(2para), pCO(2para), and pH(para)) were
      compared with partial oxygen pressure in tissue (p(ti)O(2)), laser Doppler flow,
      and systemic hemodynamic, metabolic data, and time course of transaminases.
      RESULTS: In the control group 30 and 60 min after reperfusion, the following
      values were measured: p(ti)O(2): 34.0 +/- 8.6 / 36.3 +/- 7.0 mm Hg (P < 0.05 vs.
      preop.: 49.8 +/- 12.1 mm Hg), laser Doppler area: 133.3 +/- 23.2 / 156.4 +/- 15.4
      (P < 0.05 vs. preop.: 215.9 +/- 14.8). Animals in the therapy group revealed
      significantly improved values (p(ti)O(2): 54.0 +/- 8.6 / 58.1 +/- 7.8 mm Hg,
      laser Doppler: 210.2 +/- 38.5 / 225.2 +/- 21.3; P < 0.05). Using the Paratrend,
      also an improvement in the therapy group was seen 30 and 60 min after
      reperfusion. The values showed a strong correlation with p(ti)O(2) (r = 0.895; P
      < 0.05) and laser Doppler flow (r = 0.807; P < 0.05). In the treatment group,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate
      dehydrogenase (GLDH) were reduced 6 and 18 h after reperfusion, respectively,
      indicating hepatoprotection by the therapy (P < 0.05 vs. control). CONCLUSIONS:
      The Paratrend sensor offers the opportunity to study postischemic organ
      hemodynamics through the simultaneous measurement of interstitial pH, pCO(2), and
      pO(2) in a small tissue region. This method offers a prognostic tool for the
      study of the effects of experimental vasoactive therapy on liver microcirculation
      and perspectives for continuous monitoring of human liver microperfusion after
      liver surgery and trauma.

PMID- 14709402
TI  - Does hormone replacement therapy influence retinal microvascular caliber?
AB  - Previous population-based data suggest that retinal arteriolar diameter is wider
      in women than in men. Estrogen exposures could account for this difference. To
      evaluate the effects of HRT on small blood vessels, we assessed the relationship
      between use of hormone replacement therapy (HRT) and retinal microvascular
      diameter in older women in the Blue Mountains Eye Study baseline population (n =
      1993, age >/= 49 years). Information on HRT use was recorded by trained
      interviewers. A computer-assisted program measured retinal vessel diameters from
      digitized photographs. Average arteriolar diameter was calculated as the central
      retinal arteriolar equivalent (CRAE); the lowest quintile of CRAE was considered
      generalized arteriolar narrowing. Of the 1897 women with complete data, 79 (4%)
      were premenopausal and 315 (17%), 224 (12%), and 1279 (67%) were current, past,
      and never HRT users, respectively. Among women aged < 65 years, multivariate
      adjusted mean CRAE for the four groups was 196, 198, 201, and 200 microm (P <
      0.0001), respectively. Among postmenopausal women >/= 65 years, multivariate
      adjusted mean CRAE was 187, 188, 191 microm (P < 0.0001), respectively, for
      current, past, and never users. Current HRT users were 40% more likely than never
      users to have generalized arteriolar narrowing (95% confidence interval 1.0-2.1).
      It appears that the use of HRT in older women may not have any long-term
      vasodilatory effects on retinal arterioles. These data do not support our
      hypothesis that exogenous estrogen exposures account for observed wider retinal
      arteriolar diameters in women.

PMID- 14709403
TI  - Dynamic intravital fluorescence microscopy--a novel method for the assessment of
      microvascular permeability in acute pancreatitis.
AB  - Edema formation is the first manifestation of acute pancreatitis.
      Microcirculatory derangements like leukocyte-endothelial cell interaction and
      perfusion failure result in enhancement of microvascular permeability to large
      molecules playing a pivotal role in the progression of the acutely altered
      pancreatic tissue. Due to the lack of suitable methods the crucial mechanisms of
      enhanced permeability in vivo are not very well investigated. Sprague-Dawley rats
      were randomly assigned to three groups: (a) sham operated animals with normal
      pancreas, (b) the pancreatitis group induced by 60 min temporary occlusion of the
      arterial supply followed by reperfusion and (c) the histamine group in which the
      pancreas was superfused with 10(-5)M histamine. The pharmacokinetics of
      tetramethylrhodamine-labelled BSA in the intravital microscopic images of a
      capillary network of the pancreas were densitometrically quantified over 20 min.
      From these data the effective microvascular permeability was calculated taking
      also into account morphology of microvessels, elimination rate of the tracer from
      the intravascular space and capillary microhematocrit. In addition macromolecular
      leakage of gold-labelled BSA was investigated by electron microscopy.
      Microvascular permeability was 0.10 +/- 0.02 x 10(-7) cm/s, 0.49 +/- 0.04 x 10(
      7) cm/s and 1.21 +/- 0.29 x 10(-7) cm/s for control, ischemia and histamine
      group, respectively (P < 0.05 ischemia, histamine vs. control and ischemia vs.
      histamine). Electron microscopy revealed albumin extravasation in the last two
      groups. We established a technique allowing to quantify microvascular
      permeability in pancreatic tissue by dynamic intravital microscopy being
      independent of the investigator. This technique enabling accurate
      pathophysiologic characterisation in terms of edema formation can form the basis
      for evaluating in the future novel treatment strategies directed against acute
      pancreatitis.

PMID- 14709404
TI  - Role of Rho GTPases in thrombin-induced lung vascular endothelial cells barrier
      dysfunction.
AB  - Thrombin-induced barrier dysfunction of pulmonary endothelial monolayer is
      associated with dramatic cytoskeletal reorganization, activation of actomyosin
      contraction, and gap formation. Phosphorylation of regulatory myosin light chains
      (MLC) is a key mechanism of endothelial cell (EC) contraction and barrier
      dysfunction, which is triggered by Ca(2+)/calmodulin-dependent MLC kinase (MLCK)
      and Rho-associated kinase (Rho-kinase). The role of MLCK in EC barrier regulation
      has been previously described; however, Rho-mediated pathway in thrombin-induced
      pulmonary EC dysfunction is not yet precisely characterized. Here, we demonstrate
      that thrombin-induced decreases in transendothelial electrical resistance (TER)
      indicating EC barrier dysfunction are universal for human and bovine pulmonary
      endothelium, and involve membrane translocation and direct activation of small
      GTPase Rho and its downstream target Rho-kinase. Transient Rho membrane
      translocation coincided with translocation of upstream Rho activator, guanosine
      nucleotide exchange factor p115-RhoGEF. Rho mediated activation of downstream
      target, Rho-kinase induced phosphorylation of the EC MLC phosphatase (MYPT1) at
      Thr(686) and Thr(850), resulting in MYPT1 inactivation, accumulation of diphospho
      MLC, actin remodeling, and cell contraction. The specific Rho-kinase inhibitor,
      Y27632, abolished MYPT1 phosphorylation, MLC phosphorylation, significantly
      attenuated stress fiber formation and thrombin-induced TER decrease. Furthermore,
      expression of dominant-negative Rho and Rho-kinase abolished thrombin-induced
      stress fiber formation and MLC phosphorylation. Our data, which provide
      comprehensive analysis of Rho-mediated signal transduction in pulmonary EC,
      demonstrate involvement of guanosine nucleotide exchange factor, p115-RhoGEF, in
      thrombin-mediated Rho regulation, and suggest Rho, Rho-kinase, and MYPT1 as
      potential pharmacological and gene therapy targets critical for prevention of
      thrombin-induced EC barrier disruption and pulmonary edema associated with acute
      lung injury.

PMID- 14709405
TI  - Monocyte chemoattractant protein-1 alters expression of tight junction-associated
      proteins in brain microvascular endothelial cells.
AB  - The chemokine monocyte chemoattractant protein (MCP-1) is recognized to mediate
      extravasation of mononuclear leukocytes into the brain during a variety of
      neuroinflammatory conditions. In large part produced by parenchymal neural cells
      during these disease states, it is unclear how this chemokine can stimulate the
      migration of circulating leukocytes that lie behind the highly impermeant blood
      brain barrier (BBB). Based on the premise that disruption of tight junctions
      (TJs) could foster leukocyte extravasation, experiments were conducted to test
      the hypothesis that MCP-1 alters the expression and/or distribution of the TJ
      associated proteins zonulae occludens-1 (ZO-1) and occludin in brain
      microvascular endothelial cells (BMEC) comprising the BBB. Exposure to MCP-1
      caused a loss in immunostaining of ZO-1 at inter-endothelial junctional regions
      in both cultured BMEC and isolated brain microvessels, as well as a similar
      effect on occludin in cultured BMEC, but did not alter occludin staining in
      microvessels. In cellular fractionation experiments, ZO-1 associated
      predominantly with the detergent-resistant cytoskeletal framework (CSK) in both
      cultured BMEC and brain microvessels, while a slimmer majority of occludin
      partitioned with the CSK. Following MCP-1 exposure, ZO-1 was reduced in the CSK
      fraction of cultured BMEC and microvessels, with a shift of ZO-1 to the detergent
      soluble fraction in both cases. Occludin exhibited a similar pattern of MCP-1
      induced loss and shift from the CSK in cultured BMEC, but remained nearly
      constant in microvessels. Lastly, expression of caveolin-1, a major structural
      component of membrane microdomains thought to be functionally complexed with TJs,
      was additionally altered by MCP-1 treatment of both cultured BMEC and
      microvessels. These results indicate that, in addition to its chemotactic
      activity, MCP-1 might alter BBB integrity during CNS inflammation.

PMID- 14709406
TI  - Expression of Toll-like receptors 2 and 4 on human intestinal lymphatic vessels.
AB  - The Toll-like receptor (TLR) is a part of the innate immune system sensing
      pathogen-associated molecular patterns (PAMPs). Recently, TLRs 2 and 4 have been
      demonstrated for the ligand engagements, which result in the induction of
      cytokines. Here we investigated the expression of TLRs 2 and 4 on lymphatic
      vessels producing cys-cys chemokine ligand 21 (CCL21) in the human small
      intestine. The specificity of antibodies to TLRs was tested on a human monocyte
      leukemia cell line, umbilical vein endothelial cells (HUVEC), and periodontal
      ligament fibroblasts (PDLF) with the examination for the TLR gene expression by
      the reverse transcription-polymerase chain reaction (RT-PCR), and lymphatic
      vessels were identified by antibodies for platelet-endothelial cell adhesion
      molecule-1 (PECAM-1) and desmoplakin. The expression of CCL21 was not clearly
      detected on collecting lymphatic vessels in the submucosa while it was generally
      observed on the central lacteals of villi and lymphatic capillaries in the lamina
      propria mucosae. The reaction of antibodies to TLRs 2 and 4 was also not clearly
      detected on collecting lymphatic vessels in the submucosa and central lacteals of
      villi, but generally observed on lymphatic capillaries expressing CCL21 in the
      lamina propria mucosae of tissue where the expression of CCL21 and TLRs was not
      clearly observed in blood vessels. These may suggest that the expression of
      CCL21, and TLRs 2 and 4 is predominantly induced in the peripheral lymphatic
      endothelium of the small intestinal microcirculation. The lymphatic endothelium
      may contribute to allow dendritic cells to home into secondary lymphoid tissue
      through the expression of TLRs, the ligand engagements of which result in the
      induction of chemokines.

PMID- 14709407
TI  - Integrating the roles of extracranial lymphatics and intracranial veins in
      cerebrospinal fluid absorption in sheep.
AB  - At relatively low cerebrospinal fluid (CSF) pressures, the majority of CSF
      drainage in 6- to 8-month-old sheep occurs through the cribriform plate into
      lymphatic vessels in the nasal submucosa. As CSF pressures are elevated, other
      absorption sites are recruited and these may include transport through arachnoid
      projections. To test for the transport of CSF directly into the venous sinus, the
      concentration of a tracer (131I-human serum albumin [HSA]) administered into the
      CSF compartment was measured in the confluence of the intracranial venous sinuses
      (torcular) and in the peripheral blood (inferior vena cava). CSF pressures were
      adjusted to favor absorption. Enrichment of the CSF tracer in the cranial venous
      system was most evident when the CSF-venous sinus pressure gradients were high.
      Peak concentration differences occurred 90 s after the CSF pressures were
      elevated. When pressure gradients approached 30 cm H(2)O, tracer concentrations
      in the torcular were approximately twofold higher than those observed in
      peripheral blood. The greatest concentration differences favoring the torcular
      were obtained when the CSF-venous sinus pressure gradients were elevated to high
      levels (20- to 40 cm H(2)O) and when CSF access to the paranasal lymphatics and
      CSF transport into the spinal subarachnoid compartment were prevented. In
      conjunction with previous studies, these results are compatible with the view
      that CSF absorption in the adult animal can occur directly into the cranial
      venous system. However, contrary to the established view, this pathway may
      represent a secondary system that is recruited to compliment lymphatic transport
      when global absorption capacity is stressed or compromised.

PMID- 14709408
TI  - Tumor necrosis factor alpha is not implicated in the genesis of experimental
      autoimmune gastritis.
AB  - Experimental autoimmune gastritis (EAG) characterised by mononuclear cell
      infiltrate, parietal and zymogenic cell destruction and circulating
      autoantibodies to gastric H(+)/K(+)ATPase is an animal model for human autoimmune
      gastritis, that leads to pernicious anaemia. We have previously shown that Fas
      has a role in initiating damage to target cells in EAG. Here we used three
      strategies to examine the role of TNFalpha in this disease. We administered
      neutralising anti-TNFalpha antibody either as a single injection or as twice
      weekly injections for 8 weeks to mice subjected to neonatal thymectomy-induced
      EAG. To address the role of apoptotic signals through TNFR1, TNFR1 deficient mice
      were either neonatally thymectomised or crossed to PC-GMCSF transgenic mice that
      spontaneously develop EAG. Neonatally thymectomised mice treated with anti
      TNFalpha antibody developed destructive gastritis and autoantibodies to gastric
      H(+)/K(+)ATPase similar to control mice. Following either neonatal thymectomy or
      crossing to PC-GMCSF transgenic mice, TNFR1 deficient mice developed autoantibody
      positive destructive gastritis at similar frequency compared with wild type and
      heterozygous littermates. Our observations that neutralisation of TNFalpha and
      absence of TNFR1 has no discernible effect on development of EAG suggest that
      TNFalpha is not required for mucosal cell damage or development of autoimmune
      gastritis. While blocking TNFalpha activity has therapeutic benefit in certain
      autoimmune diseases, this is not the case for EAG.

PMID- 14709409
TI  - Nasal instillation of gpMBP can exacerbate murine EAE: effect of mucosal priming
      is an age-dependent phenomenon.
AB  - Nasal installation or oral feeding of antigens can alter the subsequent immune
      response in animals and humans. Most mucosal treatments with antigens tend to
      down-regulate disease, inducing full tolerance or immune deviation; however,
      priming has also been reported. We evaluated the course of experimental
      autoimmune encephalomyelitis (EAE) in (SJL x B10.PL)F1 mice after nasal
      instillation of myelin basic protein. There was a tendency towards exacerbation
      of subsequent disease in animals if they were nasally exposed to gpMBP during the
      neonatal period (first week of life), compared to exposure during adulthood.
      Later, at 11 months of age, this tendency to exacerbate disappeared. Our results
      suggest that mucosal exposure during early life may regularly modulate the anti
      self immune response upwards in individuals genetically predisposed to autoimmune
      diseases.

PMID- 14709410
TI  - Apoptosis in feathers of Smyth line chickens with autoimmune vitiligo.
AB  - Vitiligo is an acquired dermatological disorder characterized by a loss of
      epidermal melanocytes resulting in depigmentation of the skin. Mechanisms
      underlying the destruction of melanocytes in vitiligo remain unclear. An animal
      model to study spontaneously occurring autoimmune vitiligo is the mutant Smyth
      line (SL) of chickens. This investigation was designed to determine whether the
      pathogenesis of depigmentation in Smyth line chicken vitiligo (SLV) involves an
      apoptotic mechanism. Terminal deoxynucleotide transferase-mediated fluorescein
      dUTP nick end labeling (TUNEL) was used to detect in situ cell apoptosis in
      cryostat sections of 2-week-old regenerating feathers. Two-week-old regenerating
      feathers were obtained from SL chickens and their normally pigmented controls
      including the parental Brown line (BL) and Light Brown Leghorn (LBL) chickens at
      6, 8, 10 and 12 weeks of age. In feathers from vitiliginous SL chickens, the
      number of TUNEL+ cells was significantly (P<or=0.05) higher than that in the
      feathers of non-vitiliginous SL, BL or LBL chickens. These TUNEL+ cells were
      primarily located in the epithelial barb ridge where melanocyte cell bodies are
      located. The extent of this apoptosis in the feathers of SLV chickens varied with
      the severity of depigmentation of the feathers (i.e., highest in active
      depigmentation), suggesting a close association between apoptosis and the
      disappearance of melanocytes. In addition to TUNEL staining, most sections were
      double-stained with monoclonal antibodies specific to either CD8 or MHC class II
      molecules to further explore the relationship between CD8+ feather-infiltrating
      lymphocytes and this increase in apoptotic cells. Compared to normally pigmented
      controls, the number of CD8+ and MHC class II+ cells in the feather pulp and the
      barb ridge increased 2-4 weeks before the visible onset of SLV, and was directly
      related to the changes in the number of TUNEL+ cells prior to, at onset and
      during depigmentation. Moreover, some of these infiltrating CD8+ cells were
      localized next to or near the TUNEL+ cells. These observations suggest that
      enhanced apoptosis in the feather of SLV chickens is a pathogenic mechanism
      involved in the death of melanocytes and appears to be induced by infiltrating
      cytotoxic T lymphocytes (CD8+).

PMID- 14709411
TI  - Inverse correlation between the incidences of autoimmune disease and infection
      predicted by a model of T cell mediated tolerance.
AB  - The contribution of pathogenic infections to the etiology of autoimmune diseases
      remains one of the outstanding problems in immunology. According to the classical
      concept of antigen mimicry, a direct correlation between the incidence of
      autoimmunity and infections would be expected. This view is supported by a few
      examples of autoimmune disorders, which are documented as being caused by
      infection with particular pathogens. In contrast, there are several experimental
      animal models where infection appears to prevent the onset of autoimmunity.
      Moreover, some epidemiological studies suggest an inverse correlation between the
      incidence of autoimmunity and infections in human populations. Here we propose a
      solution to this puzzle based on a theoretical model of tolerance driven by
      regulatory T cells. The concepts here developed delineate the conditions
      predicting an inverse correlation between the incidence of autoimmunity and
      exposition to common infections, and those in which antigen mimicry and
      inflammation of target organs have a role in the etiology of specific autoimmune
      disorders.

PMID- 14709412
TI  - Natural anti-FcepsilonRIalpha autoantibodies may interfere with diagnostic tests
      for autoimmune urticaria.
AB  - IgG autoantibodies against the alpha-chain of the high affinity IgE receptor are
      claimed to play a pathogenetic role in autoimmune urticaria. The best methods for
      detection of functional autoantibodies are currently the autologous serum skin
      test and the basophil histamine release assay. A simplified and feasible
      screening test would facilitate the diagnosis of autoimmune urticaria. Here we
      offer an explanation for the difficulties in establishing a screening test for
      autoantibodies directed against the alpha-chain of the high affinity IgE receptor
      in autoimmune urticaria. Identical autoantibodies in chronic urticaria patients
      and healthy donors belonging to the natural autoantibody repertoire were found by
      sequence analysis of anti-alpha-chain autoantibodies isolated by repertoire
      cloning from antibody libraries. These natural autoantibodies bound to the
      receptor and triggered histamine release but only if IgE was previously removed
      from the receptor. Diagnostic assays used for detection of antibodies directed
      against the IgE receptor may require signal comparison with and without the
      artificial removal of IgE, immune complexes, and complement in order to avoid
      false positive or negative results. After IgE removal diagnostic tests will
      detect natural autoantibodies against the high affinity IgE receptor regardless
      of whether they are pathogenic or not.

PMID- 14709413
TI  - Epitopes recognised by tissue transglutaminase antibodies in coeliac disease.
AB  - The interaction between IgA tissue transglutaminase (tTG) antibodies (Abs) and
      35S-labelled tTG produced in a transcription/translation (TnT) system with
      various amino acid (aa) deletions has been studied. These experiments showed that
      the tTG N-terminal aa 1-89 were important for tTG Ab binding in all 15 coeliac
      disease sera studied and the central residues (aa 401-491) were important for
      binding of tTG Abs in all but one sera. The contribution of C-terminal residues
      to tTG Ab binding varied in different coeliac sera but overall was less than the
      contributions of the N terminal and central regions. Mouse monoclonal antibodies
      (MAbs) to tTG were produced and the tTG aa sequences recognised by the MAbs
      determined using modified 35S-labelled tTG proteins. Analysis of the inhibiting
      effects of patient sera tTG Ab on binding of tTG MAbs to tTG confirmed the
      importance of the N-terminal and central regions of tTG in forming serum tTG Ab
      binding sites. Recombinant human tTG was expressed in yeast and purified to
      better than 95% homogeneity using MAb affinity chromatography as a final
      purification step. This material was highly suitable for use in an ELISA for
      tTGAb.

PMID- 14709414
TI  - One-step cloning of anti tissue transglutaminase scFv from subjects with celiac
      disease.
AB  - Celiac disease is characterized by intestinal mucosal injury and malabsorption
      precipitated by dietary exposure to gluten of some cereals with a prominent role
      being played by gliadins, specific antigenic determinants found in wheat gluten.
      Patients suffering from celiac disease have serum antibodies recognizing gliadin,
      as well as the endomysial autoantigen tissue transglutaminase. Phage display
      antibody libraries have revealed ectopic production of anti-transglutaminase
      antibodies by intestinal lymphocytes with a biased use of the VH5 antibody gene
      family. Here we report a study on the pairing of VH and VL families in the
      antibodies to transglutaminase. Our results led to the construction of small
      phage display antibody libraries based on the amplification of the two genes in
      the VH5 family from intestinal lymphocytes. This method can be used for the rapid
      characterization of the anti-transglutaminase response in a potentially large
      number of subjects including asymptomatic patients whose serum antibodies may be
      undetectable.

PMID- 14709415
TI  - Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G
      polymorphism in Japanese patients with type 1 diabetes.
AB  - Interleukin-18 (IL-18) is a potent proinflammatory cytokine which is strongly
      associated with the development of diabetes in NOD mice. To test the putative
      involvement of IL-18 gene polymorphism in predisposition to human type 1
      diabetes, the SNPs at position -607 (C/A) and -137 (G/C) in the promoter region
      of IL-18 gene were analyzed by sequence-specific PCR in 116 patients with type 1
      diabetes and 114 normal controls. A linkage disequilibrium found only three of
      the four possible haplotypes defined by these SNPs. The distribution of the IL-18
      gene genotypes at position -607 was significantly different between patients with
      type 1 diabetes and normal controls (P=0.023). Furthermore, there was a
      significant increase in haplotype 1 (-607C/-137G) in the patients compared with
      controls (P=0.006). The association study of the susceptible CTLA-4 genotype (GG
      at nucleotide position 49 in exon 1) or HLA-DR4-DQB1*0401 and type 1 diabetes
      showed that the predisposing IL-18 gene haplotype modulates the risk on CTLA-4 GG
      genotype, but not on HLA-DR4-DQB1*0401 haplotype. Among subjects carrying the
      CTLA-4 GG genotype, the frequency of IL-18 haplotype 1 in patients with type 1
      diabetes was significantly higher than that in controls (91% vs. 71%, P=0.012).
      However, IL-18 haplotype 1 was not frequent in patients who do not exhibit the
      CTLA-4 high-risk genotype. These results suggest that the IL-18 gene polymorphism
      is associated with a type 1 diabetes susceptibility, and there might be a gene
      gene interaction between IL-18 gene with susceptible CTLA-4 gene.

PMID- 14709416
TI  - Frequency of proteinase 3 (PR3)-specific autoreactive T cells determined by
      cytokine flow cytometry in Wegener's granulomatosis.
AB  - OBJECTIVE: Previous studies have shown proliferation to Wegener's autoantigen,
      proteinase 3 (PR3). We tested immunogenicity of PR3-derived peptides and
      determined frequencies of PR3-specific T cells using cytokine flow cytometry in
      Wegener's granulomatois (WG). METHODS: Peripheral blood T-cell responses were
      measured after stimulation with previously described PR3-derived peptides. PBMC
      were stimulated with PR3-derived peptides or control stimuli for up to 10 days.
      Cells were stained with antibodies against CD4 or CD8, CD69 and intracellular TNF
      alpha and analyzed by flow cytometry. PR3-specific T cells were counted as the
      percentage of CD69(+)TNF-alpha(+)double positive T cells after stimulation.
      RESULTS: Frequencies of PR3-specific peripheral blood T cells after short-term
      stimulation (<or=0.4%) were lower compared to frequencies of PR3-specific CD4(+)T
      cells (0.64+/-0.09%, mean+/-SEM) and PR3-specific CD8(+)T cells (0.65+/-0.18%)
      after 10 days of stimulation in WG. There were no differences of the frequency of
      PR3-specific T cells between WG and healthy controls after stimulation with other
      peptides. The frequency of PR3-specific CD8(+)T cells stimulated with a
      preferentially HLA-A*0201 binding PR3-peptide sequence was higher compared to the
      frequency of T cells stimulated with a HLA-B*0702 binding PR3-peptide in one WG
      patient whose HLA type was known (A2B7). CONCLUSION: Low frequencies of TNF
      alpha(+)PR3-specific T cells can be detected in individual WG patients and
      controls using cytokine flow cytometry. The pattern and time course of cytokine
      production in response to PR3 peptides needs to be further elucidated. Additional
      factors such as the influence of proinflammatory or regulatory T cells might be
      important for the induction of autoimmunity in WG.

PMID- 14709417
TI  - Identification of autoantibody against poly (ADP-ribose) polymerase (PARP)
      fragment as a serological marker in systemic lupus erythematosus.
AB  - OBJECTIVES: By utilizing serological analysis of a recombinant cDNA expression
      library (SEREX), we previously found that autoantibodies to poly (ADP-ribose)
      polymerase (PARP) are specifically present in the sera of patients with SLE. In
      this study, recombinant proteins of various domains of PARP were used to
      determine the PARP domain that is associated with SLE. METHODS: We produced four
      recombinant PARP proteins, which contained various PARP domains, and then carried
      out enzyme linked immunosorbent assay (ELISA) using these recombinant proteins to
      identify domains useful for SLE diagnosis. The recombinant proteins used in this
      analysis were; ADPNF (amino acids 1-234), ET-L2 (amino acids 339-680), ET-L3
      (amino acids 681-1014), and ADPCF (amino acids 300-1014). RESULT: ELISA with
      ADPNF or ET-L2 showed low sensitivity in the sera of patients with SLE (14.3% and
      17.0% respectively), whereas ELISA with ET-L3 or ADPCF showed high sensitivity in
      the sera of patients with SLE (34.0% and 49.1%, respectively). Autoantibodies to
      ADPCF were not found in the sera of patients with rheumatoid arthritis (0/30),
      systemic sclerosis (0/30) or healthy donors (0/54) and were rarely found in
      polymyositis/dermatomyositis (1/30) and Sjogren syndrome (1/14). Autoantibodies
      to ADPCF were closely associated with the presence of an oral ulcer in SLE
      (P=0.03, by the chi-square test). CONCLUSION: The high sensitivity and
      specificity shown by autoantibodies to ADPCF protein could be used as a valuable
      serologic maker for the diagnosis of SLE.

PMID- 14709418
TI  - Simulators for laparoscopic surgery: a coming of age.

PMID- 14709419
TI  - Metabolomic analysis of adrenal lipids during hypoxia in the neonatal rat:
      implications in steroidogenesis.
AB  - The nursing rat pup exposed to hypoxia from birth exhibits ACTH-independent
      increases in corticosterone and renin/ANG II-independent increases in
      aldosterone. These increases are accompanied by significant elevation of plasma
      lipid concentrations in the hypoxic neonates. The purpose of the present study
      was to compare changes in the concentrations of specific fatty acid metabolites
      and lipid classes in serum and adrenal tissue from normoxic and hypoxic rat pups.
      We hypothesized that lipid alterations resulting from hypoxia may partly explain
      increases in steroidogenesis. Rats were exposed to normoxia or hypoxia from
      birth, and pooled serum and adrenal tissue from 7-day-old pups were subjected to
      metabolomic analyses. Hypoxia resulted in specific and significant changes in a
      number of fatty acid metabolites in both serum and the adrenal. Hypoxia increased
      the concentrations of oleic (18:1 n-9), eicosapentaenoic (EPA; 20:5 n-3), and
      arachidonic (20:4 n-6) acids in the triacylglyceride fraction of serum and
      decreased oleic and EPA concentrations in the cholesterol ester fraction. In the
      adrenal, hypoxia caused an increase in several n-6 fatty acids in the
      triacylglyceride fraction, including linoleic (18:2 n-6) and arachidonic acid.
      There was also an increase in the concentration of alpha-linolenic acid (18:3 n
      3) in the triacylglyceride fraction of the hypoxic adrenal, along with an
      increase in linoleic acid concentration in the diacylglyceride fraction. We
      propose that specific changes in lipid metabolism in the adrenal, as a result of
      hypoxia, may partly explain the increased steroidogenesis previously observed.
      The mechanism responsible may involve alterations in cellular signaling and/or
      mitochondrial function. These cellular changes may be a mechanism by which the
      neonate can increase circulating adrenal steroids necessary for survival,
      therefore bypassing a relative insensitivity to normal stimuli.

PMID- 14709420
TI  - Glucose-dependent insulinotropic peptide: differential effects on hepatic artery
      vs. portal vein endothelial cells.
AB  - Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing
      effects on splanchnic blood flow. GIP infusion in dogs results in an increase in
      portal vein circulation but a drop in hepatic artery blood flow. In an effort to
      evaluate whether these different responses were related to intrinsic differences
      in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein
      endothelial cells (PVEC). We report that there are differences in GIP activation
      of the signal transduction pathways in these two cell types. GIP stimulates
      secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28
      nM) but not from PVEC. This effect could be abolished by preventing a rise in
      intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1
      secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist
      blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50
      0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct
      differences in GIP effects on HAEC from those on PVEC. We conclude that
      differences in GIP stimulation of ET-1 vs. nitric oxide production in different
      vascular beds may account for some of the observed differences in its
      physiological effects.

PMID- 14709421
TI  - Characterization of the portal signal during 24-h glucose delivery in
      unrestrained, conscious rats.
AB  - To characterize the "portal signal" during physiological glucose delivery, liver
      glycogen was measured in unrestrained rats during portal (Po) and peripheral (Pe)
      constant-rate infusion, with minimal differences in hepatic glucose load (HGL)
      and portal insulin between the delivery routes. Hepatic blood flows were measured
      by Doppler flowmetry during open surgery. Changes in hepatic glucose, portal
      insulin, glucagon, lactate, and free fatty acid concentrations were generally
      similar in either delivery except for glucagon at 4 h. Hepatic glycogen, however,
      increased continuously in Po and was higher than Pe at 8 and 24 h, although it
      decreased to the level of Pe upon the removal of Po at 8 h. There was a near
      linear relationship between hepatic glycogen and HGL in either delivery, with the
      slope being twice as high in Po and the intercepts converging to basal HGL. The
      hepatic response to Po did not alter upon 80% replacement by Pe. These results
      suggest that negative arterial-portal glucose gradients increase the rate of
      hepatic glycogen synthesis against the incremental HGL in an all-or-nothing mode.

PMID- 14709422
TI  - Trauma team activation criteria as predictors of patient disposition from the
      emergency department.
AB  - Many trauma centers use mainly physiologic, first-tier criteria and mechanism
      related, second-tier criteria to determine whether and at what level to activate
      a multidisciplinary trauma team in response to an out-of-hospital call. Some of
      these criteria result in a large number of unnecessary team activations while
      identifying only a few additional patients who require immediate operative
      intervention. OBJECTIVES: To separately evaluate the incremental predictive value
      of individual first-tier and second-tier trauma team activation criteria for
      severe injury as reflected by patient disposition from the emergency department
      (ED). METHODS: This was a prospective cohort study in which activation criteria
      were collected prospectively on all adult patients for whom the trauma team was
      activated during a five-month period at an urban, Level 1 trauma center. Severe
      injury disposition ("appropriate" team activation) was defined as immediate
      operative intervention, admission to the intensive care unit (ICU), or death in
      the ED. Data analysis consisted of recursive partitioning and multiple logistic
      regression. RESULTS: Of the 305 activations for the mainly physiologic first-tier
      criteria, 157 (51.5%) resulted in severe injury disposition. The first-tier
      criterion that caused the greatest increase in "inappropriate" activations for
      the lowest increase in "appropriate" activations was "age > 65." Of the 34
      additional activations due to this criterion, seven (20.6%) resulted in severe
      injury disposition. Of the 700 activations for second-tier, mechanism-related
      criteria, 54 (7.7%) resulted in ICU or operating room admissions, and none
      resulted in ED death. The four least predictive second-tier criteria were
      "motorcycle crash with separation of rider," "pedestrian hit by motor vehicle,"
      "motor vehicle crash with rollover," and "motor vehicle crash with death of
      occupant." Of the 452 activations for these four criteria, only 18 (4.0%)
      resulted in ICU or operating room admission. CONCLUSIONS: The four least
      predictive second-tier, mechanism-related criteria added little sensitivity to
      the trauma team activation rule at the cost of substantially decreased
      specificity, and they should be modified or eliminated. The first-tier, mainly
      physiologic criteria were all useful in predicting the need for an immediate
      multidisciplinary response. If increased specificity of the first-tier criteria
      is desired, the first criterion to eliminate is "age > 65."

PMID- 14709423
TI  - Performance of a novel clinical score, the Pediatric Asthma Severity Score
      (PASS), in the evaluation of acute asthma.
AB  - OBJECTIVES: To evaluate the reliability, validity, and responsiveness of a new
      clinical asthma score, the Pediatric Asthma Severity Score (PASS), in children
      aged 1 through 18 years in an acute clinical setting. METHODS: This was a
      prospective cohort study of children treated for acute asthma at two urban
      pediatric emergency departments (EDs). A total of 852 patients were enrolled at
      one site and 369 at the second site. Clinical findings were assessed at the start
      of the ED visit, after one hour of treatment, and at the time of disposition.
      Peak expiratory flow rate (PEFR) (for patients aged 6 years and older) and pulse
      oximetry were also measured. RESULTS: Composite scores including three, four, or
      five clinical findings were evaluated, and the three-item score (wheezing,
      prolonged expiration, and work of breathing) was selected as the PASS.
      Interobserver reliability for the PASS was good to excellent (kappa = 0.72 to
      0.83). There was a significant correlation between PASS and PEFR (r = 0.27 to
      0.37) and pulse oximetry (r = 0.29 to 0.41) at various time points. The PASS was
      able to discriminate between those patients who did and did not require
      hospitalization, with area under the receiver operating characteristic curve of
      0.82. Finally, the PASS was shown to be responsive, with a 48% relative increase
      in score from start to end of treatment and an overall effect size of 0.62,
      indicating a moderate to large effect. CONCLUSIONS: This clinical score, the
      PASS, based on three clinical findings, is a reliable and valid measure of asthma
      severity in children and shows both discriminative and responsive properties. The
      PASS may be a useful tool to assess acute asthma severity for clinical and
      research purposes.

PMID- 14709424
TI  - Interactions between emergency medicine programs and the pharmaceutical industry.
AB  - OBJECTIVES: To examine the beliefs and practices of emergency medicine program
      directors regarding interactions with the pharmaceutical industry. The authors
      also sought to study the prevalence of program policies and the desire for
      organizational policies. METHODS: The Board of the Council of Emergency Medicine
      Residency Directors (CORD) requested and approved a member survey. An
      institutional review board-approved, Web-based, 30-item survey was sent to all
      CORD members subscribed to the organization's listserv in May 2002 and was
      completed by June 2002. Program director respondents were surveyed as to their
      beliefs and practices regarding industry sponsorship of speakers, social events,
      drug samples, travel to conferences, and the educational value of marketing
      representatives. Subjects were queried about their awareness of existing
      guidelines and whether they desired policy development by CORD. RESULTS: Surveys
      were returned from 106 programs (85%). The majority of program directors (72%)
      "never" or "very rarely" allowed unrestricted interactions between pharmaceutical
      representatives and residents at work. However, only 52% of program directors
      said they "never" or "very rarely" allowed pharmaceutical representatives to give
      residents free drug samples at work. Only 46% said they "never" or "very rarely"
      allowed pharmaceutical representatives to teach residents. Two thirds of program
      directors desired CORD guidelines regarding interactions with the pharmaceutical
      industry. Program directors seeking guidelines were less likely to allow
      pharmaceutical representatives to teach residents (p = 0.001). They were also
      less likely to allow pharmaceutical representatives unrestricted interactions
      with residents (p = 0.05). CONCLUSIONS: A wide range of practices exist among
      emergency medicine residency program directors, and most desire organizational
      guidelines regarding interactions with the pharmaceutical industry.

PMID- 14709425
TI  - Reliability of a structured interview scoring instrument for a Canadian
      postgraduate emergency medicine training program.
AB  - OBJECTIVES: To determine the reliability of scores assigned to interviews of
      medical students applying to an emergency medicine program. METHODS: A scoring
      instrument was derived based on faculty and resident input, institutional and
      national documents, and previous application procedures. Candidates were
      interviewed by four pairs of interviewers. Interviewers were asked to score the
      candidates on five visual analog scales (VASs) with objective anchors. Each
      interview assessed a unique candidate characteristic. All interviewers were given
      explicit instructions on scoring procedures and instrument use. The data were
      entered into an Excel database and transferred to SPSS, and reliabilities were
      measured with a two-way mixed-effect Cronbach's alpha. RESULTS: Forty
      applications were received for the 2002 residency entry year. Thirty-eight
      application packages were complete, and 16 candidates were interviewed. Data
      collection was complete for all 16. The average measure intraclass correlations
      for each individual interviewer across the five VASs ranged from 0.72 to 0.92
      (mean, 0.85). The interrater reliability within the four interviews (personal
      characteristics, trainability, suitability for emergency medicine, and
      suitability for the specific training program) were low at 0.36, 0.59, 0.69, and
      0.49. The overall reliability of the four interview scores was 0.83, and for the
      eight interviewer scores it was 0.86. CONCLUSIONS: The reliability of the overall
      interview scores was very high. The intraclass correlations for each
      interviewer's VAS scores were also high, but interrater correlations within
      interview teams were moderate and not higher than those across interview teams.
      This study suggests that an interview assessment instrument can be highly
      reliable overall and that interviewers base scores on an overall global
      impression.

PMID- 14709426
TI  - Effectiveness of an adult-learning, self-directed model compared with traditional
      lecture-based teaching methods in out-of-hospital training.
AB  - Until recently, the U.S. Army Combat Medic School used a traditional teaching
      model with heavy emphasis on large group lectures. Skills were taught separately
      with minimal links to didactics. OBJECTIVES: To evaluate whether the adult
      learning model improves student learning in terms of cognitive performance and
      perception of proficiency in military medic training. METHODS: The study
      population was two sequential groups of randomly selected junior, enlisted,
      active duty soldiers with no prior formal emergency medical training who were
      enrolled in an experimental model of a U.S. Army Combat Medic School. The control
      population was a similar group of students enrolled in the traditional
      curriculum. Instructors were drawn from the same pool, with experimental group
      instructors receiving two weeks of training in adult-learning strategies. The
      study population was enrolled in the experimental program that emphasized the
      principles of adult learning, including small-group interactive approach, self
      directed study, multimedia didactics, and intensive integrated practice of
      psychomotor skills. Instructors and students were also surveyed at the end of the
      course as to their confidence in performing four critical skills. The survey
      instrument used a five-point scale ranging from "strongly disagree" through
      "undecided" to "strongly agree." Proficiency for this survey was defined as the
      sum of the top two ratings of "agree" or "strongly agree" to questions regarding
      the particular skill. Both experimental and control programs lasted ten weeks and
      covered the same academic content and nonacademic (e.g., physical fitness)
      requirements, and the two groups of students had similar duty days. Evaluations
      included performance on internal and National Registry of Emergency Medical
      Technicians (NREMT) written examinations and other measures of academic and
      nonacademic performance. RESULTS: One hundred fifty students (experimental n =
      81, control n = 69) were enrolled in 1999-2000. The scores for internal course
      grade, NREMT written score, and NREMT written pass rate were, respectively, 86.3,
      71.6, and 63% for the experimental group; and 85.8, 69.6, and 49% for the control
      group. The p-value was </= 0.05 for the comparison between internal course grade
      and NREMT written score, but p > 0.05 for the comparison between NREMT written
      pass rates. Students in both the adult-learning and traditional groups rated
      themselves high in proficiency, whereas instructors in the traditional group were
      generally much more modest in their rating of student proficiency than
      instructors of the adult-learning program. CONCLUSIONS: In this study setting, an
      adult-learning model offers only a modest improvement in cognitive evaluation
      scores over traditional teaching when measured at the end of the course.
      Additionally, students in the traditional teaching model assess themselves as
      proficient more frequently than instructors, whereas instructor and student
      perception of proficiency more closely matched in the adult-learning model.

PMID- 14709427
TI  - Estimating the degree of emergency department overcrowding in academic medical
      centers: results of the National ED Overcrowding Study (NEDOCS).
AB  - OBJECTIVES: No single universal definition of emergency department (ED)
      overcrowding exists. The authors hypothesize that a previously developed site
      sampling form for academic ED overcrowding is a valid model to quantify
      overcrowding in academic institutions and can be used to develop a validated
      short form that correlates with overcrowding. METHODS: A 23-question site
      sampling form was designed based on input from academic physicians at eight
      medical schools representative of academic EDs nationwide. A total of 336 site
      samplings at eight academic medical centers were conducted at 42 computer
      generated random times over a three-week period by independent observers at each
      site. These sampling times ranged from very slow to severely overcrowded. The
      outcome variable was the degree of overcrowding as assessed by the charge nurse
      and ED physicians. The full model consisted of objective data that were obtained
      by counting the number of patients, determining patients' waiting times, and
      obtaining information from registration, triage, and ancillary services. Specific
      objective data were indexed to site-specific demographics. The outcome and
      objective data were compared using a multiple linear regression to determine
      predictive validity of the full model. A five-question reduced model was
      calculated using a backward stepdown procedure. Predictive validity and
      relationships between the outcome and objective data were assessed using a mixed
      effects linear regression model, treating center as random effect. RESULTS:
      Overcrowding occurred 12% to 73% of the time (mean, 35%), with two hospitals
      being overcrowded more than 50% of the time. Comparison of objective and outcome
      data resulted in an R(2) of 0.49 (p < 0.001), indicating a good degree of
      predictive validity. A reduced five-question model predicted the full model with
      88% accuracy. CONCLUSIONS: Overcrowding varied widely between academic centers
      during the study period. Results of a five-question reduced model are valid and
      accurate in predicting the degree of overcrowding in academic centers.

PMID- 14709428
TI  - Predictors of emergency department patient satisfaction: stability over 17
      months.
AB  - OBJECTIVES: The contradictory findings reported in the emergency department (ED)
      patient satisfaction literature may be due to methodologic differences between
      studies, as well as actual differences in predictors. The authors examined the
      stability of predictors of ED patient satisfaction across multiple assessments
      over 17 months. METHODS: All patients who presented for emergency care to the
      authors' hospital during four designated time periods spanning 17 months were
      eligible. The participants were contacted by telephone and the following were
      assessed: demographics, visit characteristics, perceived waiting times,
      subjective quality of care indicators, and overall satisfaction. The authors
      computed logistic regressions to predict overall satisfaction for each of the
      four periods. They compared the results across the assessments, both visually and
      using an aggregated logistic regression, to determine the consistency of the
      final equations. Interpretations based on traditional p-value cut-offs and odds
      ratios (ORs) were compared. RESULTS: When using a p-value cut-off strategy of p <
      0.05, notable discrepancies in the predictors of overall satisfaction were
      common. Six indicators, including age, perceived wait before bed placement,
      perceived wait before physician evaluation, physician care, discharge
      instructions, and waiting time satisfaction, were statistically associated with
      satisfaction for only one of the four assessments. In contrast, examining the
      size of the ORs associated with each predictor showed far fewer discrepancies.
      Only physician care appeared to have large differences in the strength of its
      relation to overall satisfaction. This trend was confirmed by the aggregated
      logistic regression analysis. CONCLUSIONS: Using p-value cut-offs as the sole
      criterion for interpreting which variables are most important in determining ED
      patient satisfaction is ill-advised, and may lead to spurious conclusions of
      discrepant findings. Nevertheless, some determinants of ED satisfaction likely
      differ meaningfully based on the cohort that is being examined. Overgeneralizing
      conclusions derived from a single ED patient satisfaction study should be
      avoided, especially those studies that are cross-sectional and use a single site.

PMID- 14709429
TI  - Reliability and validity of scores on The Emergency Severity Index version 3.
AB  - OBJECTIVES: No widely used triage instrument accurately assesses patient acuity.
      The Emergency Severity Index (ESI) promises to facilitate reliable acuity
      assessment and possibly predict patient disposition. However, reliability and
      validity of ESI scores have not been established in emergency departments (EDs)
      outside the original research sites, and version 3 (v.3) of the ESI has not been
      evaluated. The study hypothesis was that scores on the ESI v.3 show good
      interrater reliability and predict hospital admission, admission site, and death.
      METHODS: The authors conducted an ED-based cross-sectional retrospective study of
      403 systematically selected ED records of patients who presented to an academic
      medical center. Twenty-seven variables were abstracted, including triage level
      assigned, admission status, site, and death. Using a standard process, the
      researchers determined the true triage level. Weighted kappa and Pearson
      correlation were used to calculate interrater reliability between true triage
      level and triage score assigned by the registered nurse (RN). The relationships
      between the true ESI level and admission, admission site, and death were
      assessed. RESULTS: Interrater reliability between RN ESI level and the true ESI
      level was kappa = 0.89; Pearson r = 0.83 (p < 0.001). Hospital admission by ESI
      level was as follows: 1 (80%), 2 (73%), 3 (51%), 4 (6%), and 5 (5%). A higher
      percentage of ESI level-1 and level-2 patients (40%, 12%) were admitted to the
      intensive care unit than ESI levels 3-5 (2%, 0%, 0%). Admission to telemetry for
      ESI levels 1-5 was 20%, 19%, 7%, 1%, and 0%, respectively. Three of four patients
      who died were ESI level 1 or 2. CONCLUSIONS: Scores on the ESI assigned by nurses
      have excellent interrater reliability and predict hospital admission and location
      of admission.

PMID- 14709430
TI  - A comparison of trauma intubations managed by anesthesiologists and emergency
      physicians.
AB  - Although airway management by emergency physicians has become standard for
      general emergency department (ED) patients, many believe that anesthesiologists
      should manage the airways of trauma victims. OBJECTIVES: To compare the success
      and failure rates of trauma intubations performed under the supervision of
      anesthesiologists and emergency physicians. METHODS: This was a prospective,
      observational study of consecutive endotracheal intubations (ETIs) of adult
      trauma patients in a single ED over a 46-month period. All ETIs before November
      26, 2000, were supervised by anesthesiologists (34 months), and all ETIs from
      November 26, 2000, onward were supervised by emergency physicians (12 months).
      Data regarding clinical presentation, personnel involved, medications used,
      number of attempts required, and need for cricothyrotomy were collected. Study
      outcomes were: 1) successful intubation within two attempts, and 2) failure of
      intubation. Failure was defined as inability to intubate, resulting in successful
      intubation by another specialist, or cricothyrotomy. Odds ratios (ORs) with 95%
      confidence intervals (95% CIs) were used to compare results between groups.
      RESULTS: There were 673 intubations during the study period. Intubation within
      two attempts was accomplished in 442 of 467 patients (94.6%) managed by
      anesthesiologists, and in 196 of 206 of patients (95.2%) managed by emergency
      physicians (OR = 1.109, 95% CI = 0.498 to 2.522). Failure of intubation occurred
      in 16 of 467 (3.4%) patients managed by anesthesiologists, and in four of 206
      (1.9%) patients managed by emergency physicians (OR = 0.558, 95% CI = 0.156 to
      1.806). CONCLUSIONS: Emergency physicians can safely manage the airways of trauma
      patients. Success and failure rates are similar to those of anesthesiologists.

PMID- 14709431
TI  - Out-of-hospital care of critical drug overdoses involving cardiac arrest.
AB  - OBJECTIVES: Death from acute drug poisoning, also termed drug overdose, is a
      substantial public health problem. Little is known regarding the role of
      emergency medical services (EMS) in critical drug poisonings. This study
      investigates the involvement and potential mortality benefit of EMS for critical
      drug poisonings, characterized by cardiovascular collapse requiring
      cardiopulmonary resuscitation (CPR). METHODS: The study population was composed
      of death events caused by acute drug poisoning, defined as poisoning deaths and
      deaths averted (persons successfully resuscitated from out-of-hospital cardiac
      arrest by EMS) in King County, Washington, during the year 2000. RESULTS: Eleven
      persons were successfully resuscitated and 234 persons died from cardiac arrest
      caused by acute drug poisoning, for a total of 245 cardiac events. The EMS
      responded to 79.6% (195/245), attempted resuscitation in 34.7% (85/245), and
      successfully resuscitated 4.5% (11/245) of all events. Among the 85 persons for
      whom EMS attempted resuscitation, opioids, cocaine, and alcohol were the
      predominant drugs involved, although over half involved multiple drug classes.
      Among the 11 persons successfully resuscitated, return of circulation was
      achieved in six following EMS cardiopulmonary resuscitation alone, in one
      following CPR and defibrillation, and in the remaining four after additional
      advanced life support. CONCLUSIONS: In this community, EMS was involved in the
      majority of acute drug poisonings characterized by cardiovascular collapse and
      may potentially lower total mortality by approximately 4.5%. The results show
      that, in some survivors, return of spontaneous circulation may be achieved with
      CPR alone, suggesting a different pathophysiology in drug poisoning compared with
      cardiac arrest due to heart disease.

PMID- 14709432
TI  - Clinical pearls: cerebrospinal fluid double ring sign.

PMID- 14709433
TI  - Who wrote this paper? Basics of authorship and ethical issues.

PMID- 14709434
TI  - Council of Emergency Medicine Residency Directors position on interactions
      between emergency medicine residencies and the pharmaceutical industry.

PMID- 14709435
TI  - End-of-life models and emergency department care.
AB  - Many people die in emergency departments (EDs) across the United States from
      sudden illnesses or injuries, an exacerbation of a chronic disease, or a terminal
      illness. Frequently, patients and families come to the ED seeking lifesaving or
      life-prolonging treatment. In addition, the ED is a place of transition-patients
      usually are transferred to an inpatient unit, transferred to another hospital, or
      discharged home. Rarely are patients supposed to remain in the ED. Currently,
      there is an increasing amount of literature related to end-of-life care. However,
      these end-of-life care models are based on chronic disease trajectories and have
      difficulty accommodating sudden-death trajectories common in the ED. There is
      very little information about end-of-life care in the ED. This article explores
      ED culture and characteristics, and examines the applicability of current end-of
      life care models.

PMID- 14709436
TI  - Advanced statistics: linear regression, part I: simple linear regression.
AB  - Simple linear regression is a mathematical technique used to model the
      relationship between a single independent predictor variable and a single
      dependent outcome variable. In this, the first of a two-part series exploring
      concepts in linear regression analysis, the four fundamental assumptions and the
      mechanics of simple linear regression are reviewed. The most common technique
      used to derive the regression line, the method of least squares, is described.
      The reader will be acquainted with other important concepts in simple linear
      regression, including: variable transformations, dummy variables, relationship to
      inference testing, and leverage. Simplified clinical examples with small datasets
      and graphic models are used to illustrate the points. This will provide a
      foundation for the second article in this series: a discussion of multiple linear
      regression, in which there are multiple predictor variables.

PMID- 14709437
TI  - Advanced statistics: linear regression, part II: multiple linear regression.
AB  - The applications of simple linear regression in medical research are limited,
      because in most situations, there are multiple relevant predictor variables.
      Univariate statistical techniques such as simple linear regression use a single
      predictor variable, and they often may be mathematically correct but clinically
      misleading. Multiple linear regression is a mathematical technique used to model
      the relationship between multiple independent predictor variables and a single
      dependent outcome variable. It is used in medical research to model observational
      data, as well as in diagnostic and therapeutic studies in which the outcome is
      dependent on more than one factor. Although the technique generally is limited to
      data that can be expressed with a linear function, it benefits from a well
      developed mathematical framework that yields unique solutions and exact
      confidence intervals for regression coefficients. Building on Part I of this
      series, this article acquaints the reader with some of the important concepts in
      multiple regression analysis. These include multicollinearity, interaction
      effects, and an expansion of the discussion of inference testing, leverage, and
      variable transformations to multivariate models. Examples from the first article
      in this series are expanded on using a primarily graphic, rather than
      mathematical, approach. The importance of the relationships among the predictor
      variables and the dependence of the multivariate model coefficients on the choice
      of these variables are stressed. Finally, concepts in regression model building
      are discussed.

PMID- 14709438
TI  - Frequency of incomplete abdominal aorta visualization by emergency department
      bedside ultrasound.
AB  - OBJECTIVES: To determine how often emergency physicians (EPs) scanning the
      abdominal aorta (AA) of nonfasted emergency department (ED) patients are able to
      visualize the entire AA. METHODS: The authors performed a retrospective study of
      patients receiving ultrasound (US) by EPs to rule out abdominal aortic aneurysm
      (AAA) at a suburban Level I ED. For patients being evaluated for possible AAA,
      EPs evaluated the entire length of the AA with US in short axis, making standard
      proximal, middle, and distal measurements. AAA was defined as dilation of the AA
      to >3 cm. Video of each US and data sheets were evaluated by a hospital
      credentialed sonologist for visualization of the AA. Any portions of the AA not
      visualized were noted. If one third or more of the length of the AA was not seen,
      the examination was considered inadequate, allowing for potentially missing an
      AAA. Statistical analysis included descriptive statistics. RESULTS: Ultrasounds
      of 207 patients were completed. In 35 patients (17%), a portion of the AA less
      than one third its length was not seen. In 17 patients (8%), a significant
      portion of the AA (at least one third its length) could not be visualized and
      therefore could have potentially concealed an AAA. In four patients, the AA could
      not be seen at all. There were 29 AAAs discovered (14%), and none were missed.
      CONCLUSIONS: Significant portions of AA (at least one third of its length) were
      not visualized on bedside US in 8% of nonfasted patients; this rate is higher
      than radiology studies of fasted patients receiving US for evaluation of their
      aortas.

PMID- 14709439
TI  - Customer satisfaction in a large urban fire department emergency medical services
      system.
AB  - OBJECTIVES: The purpose of this study was to determine if emergency medical
      services (EMS) customer satisfaction could be assessed using telephone-survey
      methods. The process by which customer satisfaction with the EMS service in a
      large, fire department-based EMS system is reported, and five month results are
      presented. METHODS: Ten percent of all patients transported during the period of
      October 15, 2001, through March 15, 2002, were selected for study. In addition,
      during the same period, all EMS incidents in which a patient was not transported
      were identified for contact. Customer-service representatives contacted patients
      via telephone and surveyed them from prepared scripts. RESULTS: A total of 88,528
      EMS incidents occurred during the study period. Of these, 53,649 resulted in
      patient transports and 34,879 did not. Ten percent of patients transported
      (5,098) were selected for study participation, of which 2,498 were successfully
      contacted; of these, 2,368 (94.8%) reported overall satisfaction with the service
      provided. Of the 34,879 incidents without transport, only 5,859 involved patients
      who were seen but not transported. All of these patients were selected for study.
      Of these, 2,975 were successfully contacted, with 2,865 (96.3%) reporting overall
      satisfaction. The most common reason given for nonsatisfaction in both groups was
      the perception of a long response time. CONCLUSIONS: It is possible to conduct a
      survey of EMS customer satisfaction using telephone-survey methods. Although
      difficulties exist in contacting patients, useful information is made available
      with this method. Such surveys should be an integral part of any EMS system's
      quality-improvement efforts. In this survey, the overwhelming majority of
      patients, both transported and not transported, were satisfied with their
      encounter with EMS.

PMID- 14709440
TI  - The demands of 24/7 coverage: using faculty perceptions to measure fairness of
      the schedule.
AB  - OBJECTIVES: Ensuring fair, equitable scheduling of faculty who work 24-hour, 7
      day-per-week (24/7) clinical coverage is a challenge for academic emergency
      medicine (EM). Because most emergency department care is at personally valuable
      times (evenings, weekends, nights), optimizing clinical work is essential for the
      academic mission. To evaluate schedule fairness, the authors developed objective
      criteria for stress of the schedule, modified the schedule to improve equality,
      and evaluated faculty perceptions. They hypothesized that improved equality would
      increase faculty satisfaction. METHODS: Perceived stress was measured for types
      of clinical shifts. The seven daily shifts were classified as weekday, weekend,
      or holiday (plus one unique teaching-conference coverage shift). Faculty assigned
      perceived stress to shifts (ShiftStress) utilizing visual analog scales (VAS).
      Faculty schedules were measured (ShiftScores) for two years (1998-1999), and
      ShiftScore distribution of faculty was determined quarterly. Schedules were
      modified (1999) to reduce interindividual ShiftScore standard deviation (SD). The
      survey was performed pre- and postintervention. RESULTS: Preintervention, 26
      faculty (100% of eligible) assigned VAS to 22 shifts. Increased stress was
      perceived in progression (weekday data, 0-10 scale) from day to evening to night
      (2.07, 5.00, 6.67, respectively) and from weekday to weekend to holiday (day
      shift data, 2.07, 4.93, 5.87). The intervention reduced interindividual
      ShiftScore SD by 21%. Postintervention survey revealed no change in perceived
      equality or satisfaction. CONCLUSIONS: Faculty perceived no improvement despite
      scheduling modifications that improved equality of the schedule and provided
      objective measures. Other predictors of stress, fairness, and satisfaction with
      the demanding clinical schedule must be identified to ensure the success of EM
      faculty.

PMID- 14709441
TI  - The smallpox immunization program compared with clinical research.

PMID- 14709442
TI  - Society for Academic Emergency Medicine (SAEM) Neurologic Emergencies Interest
      Group response to the SAEM Board position on optimizing care of the stroke
      patient.

PMID- 14709445
TI  - Balancing the yeses and nos.

PMID- 14709446
TI  - Biological fallacy.

PMID- 14709449
TI  - European concerted action on anticoagulation. Quality assessment of the CoaguChek
      Mini and TAS PT-NC point-of-care whole-blood prothrombin time monitors.
AB  - BACKGROUND: International Normalized Ratios (INRs) for prothrombin time obtained
      with the CoaguChek Mini and TAS (RapidPointCoag) PT-NC systems are markedly
      different and also differ from the "true" INR. There is therefore a need for
      local quality assessment (QA) of the two systems. METHODS: A set of 60
      lyophilized artificially depleted and 60 lyophilized coumarin plasmas were tested
      at 10 centers on both point-of-care testing monitors. Subsets of three and five
      plasmas were selected as QA plasmas and compared with the remaining 55 to assess
      the relative ability of the systems to characterize performance at the individual
      centers. The incidence of aberrant results (outliers; >15% deviation from the
      true INR) was also recorded. The expected incidence with the QA plasmas was
      calculated and compared. RESULTS: On both systems, INR with the common sets of 55
      lyophilized plasmas varied considerably between centers. With the TAS PT-NC,
      subsets of five and three European Concerted Action on Anticoagulation (ECAA)
      artificially depleted plasmas gave good correlation with the 55 plasmas, but the
      coumarin plasmas performed less well. With the CoaguChek Mini, correlation was
      good with sets of five artificially depleted QA plasmas and reasonable with three
      but was less satisfactory with the coumarin plasmas. Outliers were detected with
      both types of plasmas on both test systems but with variable success.
      CONCLUSIONS: With the TAS PT-NC, three ECAA artificially depleted lyophilized
      plasmas provided reliable QA, but five lyophilized coumarin plasmas were
      required. With the CoaguChek Mini, five artificially depleted plasmas gave
      reliable QA but coumarin plasmas gave poorer results. ECAA QA plasmas provide a
      local system for checking INRs obtained with monitors of both types.

PMID- 14709450
TI  - Distribution and correlates of C-reactive protein concentrations among adult US
      women.
AB  - BACKGROUND: Understanding the distribution of C-reactive protein (CRP)
      concentration among adult women in the US helps to establish the magnitude of
      women at increased risk for cardiovascular disease. METHODS: We examined the
      distribution and correlates of CRP, using data from 2205 women >or=20 years of
      age from the National Health and Nutrition Examination Survey 1999-2000. CRP was
      measured with a high-sensitivity latex-enhanced turbidimetric assay. RESULTS: CRP
      concentration ranged from 0.1 to 296.0 mg/L (median, 2.7 mg/L). After exclusion
      of women with a CRP concentration >10 mg/L, the median was 2.2 mg/L.
      Approximately 25.7% of women, representing approximately 26.8 million women, did
      not report using hormone replacement therapy and had a CRP concentration >3.0 to
      10 mg/L, a category considered to indicate high risk for cardiovascular disease.
      Multiple linear regression analysis included age, race or ethnicity, education,
      smoking status, total cholesterol concentration, triglyceride concentration,
      systolic blood pressure, waist circumference, and concentrations of glucose,
      insulin, c-peptide, and glycated hemoglobin. CRP concentration varied by race or
      ethnicity (Mexican American > white) and hormone replacement therapy (users >
      nonusers). In addition, significant and independent associations existed between
      CRP and waist circumference, total cholesterol and triglyceride concentrations,
      and systolic blood pressure but not age, smoking status, alcohol use, insulin
      concentration, glycated hemoglobin, and c-peptide concentration. CONCLUSION:
      Large numbers of US women have an increased concentration of CRP.

PMID- 14709451
TI  - Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute
      tubular necrosis.
AB  - BACKGROUND: Acute tubular necrosis (ATN) has high mortality, especially in
      patients who require renal replacement therapy (RRT). We prospectively studied
      the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins
      and enzymes as predictors of a need for RRT in ATN. METHODS: In 73 consecutive
      patients with initially nonoliguric ATN, we measured urinary excretion of
      alpha(1)- and beta(2)-microglobulin, cystatin C, retinol-binding protein, alpha
      glutathione S-transferase, gamma-glutamyltransferase, lactate dehydrogenase, and
      N-acetyl-beta-D-glucosaminidase early in the course of ATN. RESULTS: Twenty-six
      patients (36%) required RRT a median of 4 (interquartile range, 2-6) days after
      detection of proteinuria and enzymuria. Patients who required RRT had higher
      urinary cystatin C and alpha(1)-microglobulin [median (interquartile range), 1.7
      (1.2-4.1) and 34.5 (26.6-45.1) g/mol of creatinine] than patients who did not
      require RRT [0.1 (0.02-0.5) and 8.0 (5.0-17.5) g/mol of creatinine]. Urinary
      excretion of cystatin C and alpha(1)-microglobulin had the highest diagnostic
      accuracies in identifying patients requiring RRT as indicated by the largest
      areas under the ROC curves: 0.92 (95% confidence interval, 0.86-0.96) and 0.86
      (0.78-0.92), respectively. Sensitivity and specificity were 92% (95% confidence
      interval, 83-96%) and 83% (73-90%), respectively, for urinary cystatin C >1 g/mol
      of creatinine, and 88% (78-93%) and 81% (70-88%) for urinary alpha(1)
      microglobulin >20 g/mol of creatinine. CONCLUSION: In nonoliguric ATN, increased
      urinary excretion of cystatin C and alpha(1)-microglobulin may predict an
      unfavorable outcome, as reflected by the requirement for RRT.

PMID- 14709452
TI  - Regional anesthesia, block room and efficiency: putting things in perspective.

PMID- 14709453
TI  - Obstructive sleep apnea and tonsillectomy: do we have a new indication for
      extended postoperative observation?

PMID- 14709454
TI  - A risk adapted approach reduces the overall institutional incidence of
      postoperative nausea and vomiting.
AB  - PURPOSE: Routine prophylactic antiemetic treatment of surgical patients appears
      justified only in case of an increased risk of postoperative nausea and vomiting
      (PONV). The objective of this investigation was to assess the feasibility and
      efficacy of a dichotomized risk score adapted management of PONV based on
      ondansetron prophylaxis and treatment with respect to the overall institutional
      rate of PONV. METHODS: After estimating the individual PONV risk by a simplified
      score, 162 adult patients scheduled for elective surgery received either 4 mg
      ondansetron intravenously (two to four risk factors = high-risk) or no
      prophylaxis (zero to one risk factor = low-risk). For antiemetic treatment
      ondansetron was given intravenously and orally. Incidence of PONV was recorded
      during the first 24 hr after recovery. RESULTS: Data from 159 subjects were
      analyzed with 44 patients classified as low-risk and 115 patients classified as
      high-risk. Nine low-risk and 58 high-risk patients experienced PONV. The expected
      institutional PONV incidence of 47% was reduced to 36%. Treatment with
      ondansetron was necessary in seven low-risk and 37 high-risk patients with a
      complete response rate of 71% (low-risk) and 43% (high-risk). CONCLUSION:
      Providing antiemetic prophylaxis with ondansetron to high-risk patients strictly
      based on a simplified risk score can reduce the overall institutional rate of
      PONV. However, classifying patients into two groups while using ondansetron as
      the single antiemetic in the high-risk group appears to be of limited efficacy as
      the incidence of PONV in high-risk patients is still double that of low-risk
      patients.

PMID- 14709455
TI  - Remifentanil provides better analgesia than alfentanil during breast biopsy
      surgery under monitored anesthesia care.
AB  - PURPOSE: To compare the analgesic effects of remifentanil and alfentanil during
      breast biopsy under monitored anesthesia care (MAC). METHODS: Sixty patients
      received sedation with propofol (50 microg.kg(-1).min(-1)). After receiving a
      loading dose of opioid (either remifentanil 0.5 microg.kg(-1), or alfentanil 2.5
      microg.kg(-1)), an infusion was initiated (remifentanil 0.05 microg.kg(-1).min(
      1) or alfentanil 0.25 microg.kg(-1).min(-1)), and this was supplemented with
      local anesthetic infiltration. The pain was evaluated with a ten-point visual
      analogue scale (VAS) during local anesthetic infiltration and deep tissue
      dissection. Inadequate analgesia, defined as VAS scores > or = 5, was treated
      first with boluses of opioid (remifentanil group 10 microg or alfentanil group 50
      microg) and if inadequate after two treatments with additional local anesthetic.
      Postoperative times were recorded including the times until discharge criteria
      were achieved and patient's actual discharge. RESULTS: The pain scores were
      similar between the two groups during the initial injections of local anesthetic
      in the breast, however, patients in the remifentanil group had lower mean pain
      scores during deep tissue dissection (2.3 vs 4.3, P < 0.01). Patients in the
      remifentanil group required fewer rescue doses of opioid (1.9 vs 3.6, P < 0.03)
      and local anesthetic (5 vs 15, P < 0.006). The two study groups had comparable
      speed of recovery. CONCLUSION: Remifentanil was a better opioid choice than
      alfentanil for breast biopsy under MAC at the doses studied, but it did not
      increase the rapidity in which patients recovered postoperatively.

PMID- 14709456
TI  - Midazolam causes less sedation in volunteers with red hair.
AB  - PURPOSE: We studied sedation, cognition, and mood during midazolam infusion in
      volunteers with red and non-red (blond or brown) hair, to test the hypothesis
      that patients with red hair may require more drugs to attain desired levels of
      sedation. METHODS: Twenty red and 19 non-red hair subjects were studied in a
      randomized, placebo-controlled cross-over design. Subjects were studied during
      placebo and midazolam at 30 ng.mL(-1) target effect site concentration. Sedation
      was assessed using the observer's assessment of alertness/sedation (OAA/S) scale,
      the drowsiness visual analogue scale (VAS), and the bispectral index; cognition
      was assessed using the Repeatable Battery for Assessment of Neuropsychological
      Status; and mood was assessed using the bipolar form of the Profile of Mood
      States (POMS). RESULTS: Red hair volunteers showed significantly higher OAA/S (P
      < 0.01) and lower drowsiness VAS (P < 0.05) scores compared to non-red hair
      subjects during midazolam infusion. Visuospatial score was significantly higher
      in subjects with red compared to non-red hair during placebo and midazolam
      trials. Delayed memory score was significantly higher during midazolam infusion
      in subjects with red compared to non-red hair. There were no group differences in
      POMS during either trials. CONCLUSION: Midazolam appears to cause significantly
      less sedation and cognitive impairment in red haired subjects.

PMID- 14709457
TI  - Tranexamic acid reduces the need for allogenic red blood cell transfusions in
      patients undergoing total hip replacement.
AB  - PURPOSE: This prospective randomized double-blind trial evaluates the efficacy of
      tranexamic acid (TA) to decrease blood losses and red blood cell transfusions in
      patients undergoing primary unilateral total hip replacement (THR). METHODS:
      Forty ASA class I to III patients received either iv TA 10 mg.kg(-1) bolus before
      surgery plus a 1 mg.kg(-1).hr(-1) infusion until wound closure (Group TA) or a
      placebo (Group P). Red blood cell transfusions were administered according to a
      standardized protocol. RESULTS: One patient of Group P was excluded because of an
      erroneous diagnosis at enrollment. Total measured blood losses (Group TA: 1308 +/
      462 mL vs Group P: 1469 +/- 405 mL), preoperative hemoglobin levels (Group TA:
      130.4 +/- 12.5 g.L(-1) vs Group P: 131.4 +/- 12.8 vs g.L(-1)), and seven-day
      postoperative hemoglobin values (Group TA: 97.8 +/- 11.8 g.L(-1) vs Group P:
      102.9 +/- 12.2 g.L(-1)) were similar. Autologous whole blood was available in
      five patients of Group P and seven patients of Group TA. Fewer patients in Group
      TA required red blood cells (Group TA: 6/20 vs Group P: 13/19; P = 0.026) and
      allogenic red blood cell transfusions (Group TA: 0/20 vs Group P: 8/19; P =
      0.0012). The median number of transfused unit per patient was also significantly
      less in patients of Group TA (0 unit) than in Group P (2 units; P = 0.03).
      CONCLUSION: TA did not change measured blood losses but reduced red blood cell
      transfusion requirements in patients undergoing primary unilateral THR.

PMID- 14709458
TI  - Rapid preparation of severe uncontrolled thyrotoxicosis due to Graves' disease
      with Iopanoic acid--a case report.
AB  - PURPOSE: To report the rapid preoperative preparation of a case of thyrotoxicosis
      due to Graves' disease resistant to medical treatment. CLINICAL FEATURES: A 14-yr
      old boy presented with a history of progressive swelling in the neck. Signs and
      symptoms were compatible with hyperthyroidism. Thyroid function tests revealed:
      serum T4 296.5 nmol.L(-1), serum T3 6.06 nmol.L(-1) and serum thyroid-stimulating
      hormone < 0.15 mIU.L(-1). The diagnosis of thyrotoxicosis due to Graves' disease
      was made. Therapy was instituted with carbimazole 30 mg.day(-1) and propranolol
      80 mg.day(-1), which were gradually increased to carbimazole 80 mg.day(-1) and
      propranolol 120 mg.day(-1), without response. Preparation was attempted by adding
      Iopanoic acid 500 mg four times a day and dexamethasone 0.5 mg four times a day
      in addition to the above drugs for five days. T3 levels declined to 1.8 nmol.L(
      1), but the serum T4 remained elevated. Symptoms of hyperthyroidism persisted but
      with decreased intensity. As the patient could not be made euthyroid, surgery was
      planned to relieve the symptoms. Anesthesia was uneventful except for
      intraoperative and postoperative tachycardia, which was managed successfully with
      esmolol. CONCLUSION: In life threatening thyrotoxicosis refractory to medical
      treatment, Iopanoic acid may be used as an adjuvant to antithyroid drugs for
      rapid preparation of the patient prior to surgery.

PMID- 14709459
TI  - Brachial plexus anesthesia compared to general anesthesia when a block room is
      available.
AB  - PURPOSE: Regional anesthesia is often felt to be beneficial to patient care but
      detrimental to operating room (OR) efficiency. In this report we compare how a
      block room (BR) affects OR time (ORT) utilization for brachial plexus anesthesia
      (BPA) in a busy upper limb practice. We also compare how anesthetic technique,
      BPA or general anesthesia (GA), impacts on the time to recovery and discharge in
      patients having outpatient upper limb surgery. METHODS: With the Ethics
      Committee's approval, a prospective study using hospital databases was
      undertaken. All patients presenting for surgery on the upper limb between
      November 1999 and April 2000 were eligible for analysis. A comparison was made of
      the various time intervals that comprise a patient's hospital stay for either GA
      or BPA. Demographic data (ASA, age, outpatient status), and location of BPA were
      analyzed. RESULTS: Use of the BR for BPA significantly reduced the pre-procedure
      anesthesia ORT when compared to BPA done in the OR (11.4 vs 32.9 min, P < 0.05;
      GA pre-procedure time was 17.8 min). In the ambulatory patient, BPA alone reduced
      post procedure anesthesia ORT, postanesthetic care unit, surgical day care unit,
      and total hospital times when compared to those receiving GA. On average those
      receiving a BPA spent 1.5 hr less in hospital (P < 0.01). Additionally, fewer
      admissions (2.4 vs 5.4%) occurred in the BPA group. CONCLUSION: The use of a BR
      reduces the anesthesia ORT associated with BPA. Secondly, BPA improves the
      recovery time phase of outpatients undergoing surgery on the upper limb.

PMID- 14709460
TI  - The posterior lumbar plexus (psoas compartment) block and the three-in-one
      femoral nerve block provide similar postoperative analgesia after total knee
      replacement.
AB  - PURPOSE: To compare the efficacy of a continuous posterior lumbar plexus (PSOAS)
      block to a continuous three-in-one femoral nerve (FEM) block in patients
      undergoing primary total knee replacement (TKR). METHODS: Sixty patients were
      randomly allocated to receive iv patient-controlled morphine analgesia (PCA), PCA
      plus a continuous FEM block with 30 mL ropivacaine 0.5% and epinephrine 1:200,000
      bolus followed by an infusion of ropivacaine 0.2% at 12 mL.hr(-1) for 48 hr, or
      PCA plus a continuous PSOAS block with the same bolus and infusion regimen as the
      FEM group. Postoperative morphine consumption, verbal analogue scale pain scores
      at rest and during physiotherapy, and evidence of sensory and motor blockades
      were noted. RESULTS: Both regional techniques significantly reduced 48 hr
      morphine consumption (FEM 37.3 +/- 34.7 mg, P = 0.0002; PSOAS 36.1 +/- 25.8 mg, P
      < 0.0001) compared to PCA (72.2 +/- 26.6 mg). Pain scores at rest, six and 24 hr
      after TKR were lower in the FEM and PSOAS groups compared to the PCA group (P <
      0.0001). Although sensory and motor blockades of the obturator nerve were
      achieved more often in the PSOAS group than in the FEM group (P < 0.0001),
      morphine consumption and pain scores did not differ between the two groups.
      CONCLUSION: Both continuous PSOAS block and continuous three-in-one FEM block
      provided better analgesia than PCA but no differences were seen between the two
      regional techniques.

PMID- 14709461
TI  - Ropivacaine plasma concentrations are similar during continuous lumbar plexus
      blockade using the anterior three-in-one and the posterior psoas compartment
      techniques.
AB  - PURPOSE: To compare ropivacaine blood concentrations obtained after a continuous
      lumbar plexus block performed either by the anterior three-in-one femoral (FEM)
      technique or the posterior (psoas compartment; PSOAS) technique. METHODS: As a
      substudy of a larger clinical trial, 24 patients were randomly allocated to
      receive a bolus of 30 mL of ropivacaine 0.5% plus epinephrine 1:200,000 followed
      by an infusion of ropivacaine 0.2% at 12 mL.hr(-1) for 48 hr via one of the two
      continuous lumbar plexus block techniques. Plasma ropivacaine concentrations, up
      to 48 hr, were measured by high performance liquid chromatography. RESULTS: Mean
      plasma ropivacaine concentrations were higher in the PSOAS group at 15, 30, and
      60 min (two-way analysis of variance, P < 0.0001) but areas under the curve were
      similar for both groups (FEM 452.4 +/- 253.6 mg.hr(-1).L(-1), PSOAS 433.4 +/-
      99.0 mg.hr(-1).L(-1)). Mean maximal plasma concentrations were observed at 48 hr
      and were comparable for the two techniques (FEM 2630.9 +/- 1470.3 ng.L(-1), PSOAS
      2325.1 +/- 604.2 ng.mL(-1)). There was no correlation between blood
      concentrations at 48 hr and body weight (r2 = 0.085, P = 0.21). One patient in
      the FEM group achieved a concentration of 6201 ng.mL(-1) at 48 hr. CONCLUSIONS:
      Although the posterior PSOAS block results in higher early plasma concentrations
      of local anesthetic than the anterior three-in-one FEM block, both techniques are
      equivalent with regards to their potential toxicity when a continuous infusion is
      administered. Local anesthetic accumulation occurs with an infusion of
      ropivacaine 0.2% at 12 mL.hr(-1) and can lead to potentially dangerous
      concentrations at 48 hr.

PMID- 14709462
TI  - Massive hemorrhage in a previously undiagnosed abdominal pregnancy presenting for
      elective Cesarean delivery.
AB  - PURPOSE: To report a case of previously undiagnosed abdominal pregnancy diagnosed
      at the time of Cesarean section for persistent oblique lie. Delivery of the fetus
      was followed by near catastrophic hemorrhage. The management of massive
      hemorrhage in the context of the obstetric patient is discussed. CLINICAL
      FEATURES: A 32-yr-old, ASA 1 primigravida was scheduled for elective Cesarean
      delivery at 38 weeks gestation under general anesthesia for a persistent oblique
      lie. On opening the abdomen, the extra-uterine position of the fetus became
      obvious. Delivery of the fetus was accompanied by torrential hemorrhage. A
      portion of the placenta was non-resectable and, following surgery, the patient
      was sent to the intensive care unit. The patient continued to lose blood and was
      returned to the operating room soon after. The abdomen was packed with large
      swabs and the wound left open. The hemorrhage continued and the application of
      military anti-shock trousers (MAST suit) helped stem the loss. A total of 36 U of
      red cells, 20 U of fresh frozen plasma, 7 U of platelets and 10 U of
      cryoprecipitate were transfused perioperatively. Both the baby and the mother
      survived. CONCLUSION: Massive hemorrhage in obstetric patients is a major test
      for the anesthetic and obstetric teams. As our experience shows, a
      multidisciplinary team based approach helped manage this crisis. Obstetric
      patients are often young and have great physiological reserve. In this case we
      feel that the MAST suit significantly contributed to the positive outcome.

PMID- 14709463
TI  - Children with severe OSAS who have adenotonsillectomy in the morning are less
      likely to have postoperative desaturation than those operated in the afternoon.
AB  - PURPOSE: To determine, in a subset of children previously reported, if the time
      of day when adenotonsillectomy for severe obstructive sleep apnea syndrome (OSAS)
      was performed affected the incidence of postoperative respiratory complications.
      CLINICAL FEATURES: Children having adenotonsillectomy were included if they had a
      polysomnographic diagnosis of severe OSAS within six months prior to operation.
      Patients who met the inclusion criteria were grouped by the occurrence of
      postoperative desaturation into a saturated (SAT) and desaturated (deSAT) group.
      The charts of children in group deSAT were reviewed. The clock time of the
      surgical procedure was recorded and categorized as morning (AM) or afternoon
      (PM). RESULTS: Eighty-eight patients met the inclusion criteria. There were 31
      girls and 57 boys. The mean +/- SD age (yr) and weight (kg) were 4.6 +/- 2.9 yr
      and 20.8 +/- 14.5 kg respectively. There were 63 children in the SAT group and 25
      in the deSAT group. Differences in age, weight and gender were not significant.
      The preoperative oxygen saturation (SaO2) nadir for the SAT and deSAT groups was
      80.8 +/- 10.2% and 67.6 +/- 17.5% (P < 0.05) respectively. The preoperative
      obstructive apnea and hypopnea index was 15.8 +/- 10.2 and 35.7 +/- 34.6
      events.hr(-1) (P < 0.05), respectively. Surgery in 63 (71.6%) children was
      performed in the AM. Univariate logistic regression identified PM surgery [odds
      ratio (OR) 4.6, 95% confidence interval (CI) 1.7 to 12.6, P = 0.002] and a
      preoperative SaO2 nadir < 80% (OR 3.6, 95% CI 1.4 to 9.4, P = 0.009) as risk
      factors predicting postadenotonsillectomy desaturation. CONCLUSION: Children with
      severe OSAS whose surgery is performed in the AM are less likely to desaturate
      following adenotonsillectomy than children whose surgery is performed in the PM.

PMID- 14709464
TI  - Repair of incarcerated inguinal hernia in an infant with acute viral
      bronchiolitis.
AB  - PURPOSE: To describe the anesthetic concerns and management options in an infant
      with acute viral bronchiolitis who required emergency surgery. CLINICAL FEATURES:
      A 12-week-old infant presented to the emergency department with an incarcerated
      right inguinal hernia. The history was complicated by concurrent acute
      bronchiolitis. As the hernia was irreducible, emergency surgery was required.
      General endotracheal anesthesia, following a rapid sequence induction, was
      supplemented with a caudal epidural block. Inhaled salbutamol and suctioning for
      thick tracheal secretions were required and were found to be clinically useful.
      The baby made a good postoperative recovery. CONCLUSIONS: A variety of techniques
      may be used to anesthetize the infant with concurrent acute bronchiolitis. In
      this case a good outcome was achieved with combined general and regional
      anesthesia, together with the use of inhaled salbutamol.

PMID- 14709465
TI  - Laryngeal damage due to an unexpectedly large and inappropriately designed cuffed
      pediatric tracheal tube in a 13-month-old child.
AB  - PURPOSE: To present a case of laryngeal damage in an infant caused by a too large
      and inappropriately designed cuffed tracheal tube. CLINICAL FEATURES: A 13-month
      old child undergoing cardiac surgery was intubated with an uncuffed endotracheal
      tube with an internal diameter (ID) of 4.0 mm. Because of an important air leak
      around the tracheal tube during mechanical ventilation, a cuffed endotracheal
      tube ID 4.0 mm was inserted. The air leak with the tube cuff not inflated was
      acceptable at 25 cm H2O airway pressure. After extubation on the third
      postoperative day, the patient showed increasing stridor and respiratory
      deterioration. Fibreoptic laryngoscopy of the spontaneously breathing patient
      showed a large intra-laryngeal web. After surgical removal of the web, the child
      rapidly recovered and was discharged from the hospital on the 12th postoperative
      day. Inspection of the 4.0 mm (ID) cuffed tracheal tube revealed a cuff
      positioned inappropriately high and an increase of 0.7 mm in outer tube diameter
      compared to the 4.0 mm (ID) uncuffed tracheal tube from the same manufacturer.
      The tube cuff is likely to be situated within the larynx when placed in
      accordance to insertion depth formulas or radiological criteria, as used for
      uncuffed tracheal tubes in children. CONCLUSION: The larger than expected
      tracheal tube with its intra-laryngeal cuff position in a 13-month-old child
      likely caused mucosal damage and an inflammatory reaction within the larynx
      resulting in granulation tissue formation and fibrous healing around the tracheal
      tube.

PMID- 14709466
TI  - Best evidence in critical care medicine: Therapeutic hypothermia to improve
      neurologic outcome after cardiac arrest.

PMID- 14709467
TI  - High frequency oscillatory ventilation in the management of a high output
      bronchopleural fistula: a case report.
AB  - PURPOSE: To describe the use of high frequency oscillatory ventilation (HFOV) in
      the management of a high output bronchopleural fistula (BPF). CLINICAL FEATURES:
      A 55-yr-old female developed a BPF after thoracotomy and decortication of an
      empyema. The patient deteriorated on the second postoperative day (pH 7.10 PCO2
      89) requiring 100% oxygen and mechanical ventilation. After initial improvement,
      deterioration occurred by 24 hr with conventional positive pressure ventilation
      (volume or pressure limited) because of decreased pulmonary compliance and
      bilateral diffuse airspace disease (acute respiratory distress syndrome),
      persistent increased peak and plateau airway pressures, a prolonged inspired
      oxygen concentration greater than 0.6, and inability to apply positive end
      expiratory pressures because of an increased BPF leak (530 mL.breaths(-1)). HFOV
      was initiated and maintained for 28 days until resolution of the airspace disease
      and decreased leak through the BPF to 100 mL.breaths(-1). CONCLUSION: We report
      the successful use of HFOV in a patient with high output BPF. We suggest that
      HFOV is a useful technique in patients with a BPF when conventional positive
      pressure ventilation fails.

PMID- 14709468
TI  - Recurrent cytomegalovirus disease, visceral leishmaniosis, and Legionella
      pneumonia after liver transplantation: a case report.
AB  - PURPOSE: Recurrent cytomegalovirus (CMV) disease is a frequent complication of
      liver transplantation. Visceral leishmaniosis in a transplant recipient is, on
      the other hand, extremely rare and only two cases of kala-azar have been
      described after liver transplantation. Immunosuppressed patients are known to be
      at risk of Legionella infection and the relationship between infection with this
      organism and hospital water supplies has been well described. These three
      diseases carry a high mortality rate. Our report examines the potential
      relationship between these complications. CLINICAL FEATURES: We describe the case
      of a liver transplant recipient who presented the three complications
      successively and survived. After reviewing the literature, we explore hypotheses
      linking these infections and discuss treatment strategies. CONCLUSIONS: In the
      patient described, infection with leishmania probably occurred months prior to
      the clinical presentation, a delay that matches the incubation period of kala
      azar. The simultaneous onset of leishmaniosis and of a high CMV viremia may have
      been a coincidence. However, CMV infection has been shown to be an independent
      predictor of invasive fungal infection in liver transplant recipients. CMV does
      indeed have a suppressive effect on the humoral and cellular immune response in
      vitro as well as in vivo. The clinical manifestations of leishmaniosis may,
      therefore, have been precipitated in this patient by the additive
      immunosuppressive effect of antirejection drugs and CMV.

PMID- 14709471
TI  - Successful aspiration of blood does not exclude malposition of a large-bore
      central venous catheter.

PMID- 14709469
TI  - An additional explanation for atrioventricular block after the administration of
      atropine.

PMID- 14709472
TI  - Sensory breast skin dermatome testing in a parturient with previous breast
      surgery can be unreliable.

PMID- 14709473
TI  - [Peripheral venous cannulation in patients with "no more veins"].

PMID- 14709475
TI  - PDA's: are we there yet?

PMID- 14709476
TI  - Epidural anesthesia in a patient with hyperkalemic periodic paralysis undergoing
      orthopedic surgery.

PMID- 14709477
TI  - Labour analgesia in a parturient with lumbar tattoo: a routine management? or
      not?

PMID- 14709478
TI  - Altered bupivacaine pharmacokinetics by MgSO4 in rats.

PMID- 14709480
TI  - Videolaryngoscopy in the management of the difficult airway.

PMID- 14709482
TI  - Videolaryngoscopy in the management of the difficult airway.

PMID- 14709483
TI  - Nasotracheal intubation, epistaxis and atelectasis in a patient with anhidrotic
      ectodermal dysplasia.

PMID- 14709484
TI  - Warming the tracheal tube and kinking.

PMID- 14709485
TI  - Nitrous oxide added to propofol does not influence the increase in cerebral blood
      flow velocity elicited by surgical stimulation.

PMID- 14709486
TI  - NHS direct.

PMID- 14709487
TI  - Colonic transit times and behaviour profiles in children with defecation
      disorders.

PMID- 14709488
TI  - Health economics in paediatrics.

PMID- 14709489
TI  - Blood transfusion.

PMID- 14709490
TI  - Massacre of the innocents.

PMID- 14709491
TI  - Variations in neurodegenerative disease across the UK: findings from the national
      study of Progressive Intellectual and Neurological Deterioration (PIND).
AB  - AIMS: To identify any UK children with variant Creutzfeldt-Jakob disease (vCJD)
      and obtain information about the causes of progressive intellectual and
      neurological deterioration (PIND) and the geographical distribution of cases.
      METHODS: The PIND Study uses the monthly surveillance card that is sent to all UK
      paediatricians by the British Paediatric Surveillance Unit. Case details are
      obtained from the reporting paediatricians by telephone interview, site visit, or
      self completion of a questionnaire. A paediatric neurology expert group then
      classifies the anonymised cases. The Communicable Disease Surveillance Centre
      (CDSC) provides mapping support. RESULTS: After five years and five months of
      surveillance, 1400 children had been reported. In the UK the majority of PIND
      cases had a confirmed diagnosis (comprising 99 different conditions); 505 "no
      cases" and 97 "outstanding" cases were excluded. A total of 798 PIND cases were
      included as follows: 577 with a confirmed underlying diagnosis; six with definite
      or probable vCJD, 51 who had undiagnosed PIND but were not thought to have vCJD,
      and 164 cases who were still under investigation. In some districts there were
      unexpectedly high numbers of PIND cases with a heterogeneous mixture of
      underlying diagnoses. In the five districts with the largest numbers of resident
      cases the majority not only came from a particular ethnic group but also had high
      reported rates of consanguinity. CONCLUSIONS: In districts with large numbers of
      PIND cases there are major resource implications. These children and their
      families have complex problems and they need access to diagnostic facilities and
      appropriate service provision.

PMID- 14709493
TI  - Colonic transit times and behaviour profiles in children with defecation
      disorders.
AB  - AIMS: To evaluate children referred for defecation disorders using the child
      behavioural checklist (CBCL). METHODS: A total of 215 patients were divided into
      three groups: 135 (5-14 years of age) with paediatric constipation (PC), 56 (5-17
      years) with functional non-retentive faecal soiling (FNRFS), and 24 (5-16 years)
      with recurrent abdominal pain (RAP). Behavioural scores were correlated with
      colonic transit time (CTT) and anorectal function parameters (manometry and EMG).
      RESULTS: No significant differences in the mean CBCL scores were found among the
      three patient groups. However, children with PC and FNRFS had significantly more
      behavioural problems than the Dutch normative sample, while children with RAP had
      scores within the normal range. No significant differences were found between CTT
      in the patient groups, with respect to the CBCL. Similarly, no significant
      difference existed between children able or unable to relax their pelvic floor
      muscles during defecation attempts and their behaviour profiles. CONCLUSION:
      There seems to be no relation between colonic/anorectal function and specific
      behavioural profiles. On the other hand, children with defecation disorders show
      more behavioural problems than do controls.

PMID- 14709494
TI  - Personality functioning: the influence of stature.
AB  - BACKGROUND: The Wessex Growth Study has monitored the psychological development
      of a large cohort of short normal and average height control participants since
      school entry. AIMS: To examine the effect of stature on their personality
      functioning now that they are aged 18-20 years. METHODS: This report contains
      data from 48 short normal and 66 control participants. Mean height SD score at
      recruitment was: short normals -2.62 SD, controls -0.22 SD. Final height SD score
      was: short normals -1.86, controls 0.07. The Adolescent to Adult Personality
      Functioning Assessment (ADAPFA) measures functioning in six domains: education
      and employment, love relationships, friendships, coping, social contacts, and
      negotiations. RESULTS: No significant effect of recruitment height or final
      height was found on total ADAPFA score or on any of the domain scores.
      Socioeconomic status significantly affected total score, employment and
      education, and coping domain scores. Gender had a significant effect on total
      score, love relationships, coping, and social contacts domain scores. Salient
      aspects of daily living for this sample were identified from the interviews
      (prevalence%): consuming alcohol (94%), further education (63%), love
      relationships (55%), current drug use (29%), experience of violence (28%),
      parenthood (11%), and unemployment (9%). Stature was not significantly related to
      behaviour in any of these areas. CONCLUSIONS: Despite previously reported links
      between short stature and poorer psychosocial adaptation, no evidence was found
      that stature per se significantly affected the functioning of the participants in
      these areas as young adults.

PMID- 14709496
TI  - Comparison of evoked arousability in breast and formula fed infants.
AB  - BACKGROUND: Currently, there is no consistent evidence that breast feeding
      reduces the risk for sudden infant death syndrome (SIDS). Arousal from sleep is
      believed to be an important survival mechanism that may be impaired in victims of
      SIDS. Previously it has been shown that arousability is impaired by the major
      risk factors for SIDS such as prone sleeping and maternal smoking. AIMS: To
      establish whether arousability was altered by method of feeding, and whether
      breast fed infants would have lower arousal thresholds. METHODS: Forty three
      healthy term infants were studied using daytime polysomnography on three
      occasions: 2-4 weeks post-term, 2-3 months post-term, and 5-6 months post-term.
      Multiple measurements of arousal threshold (cm H(2)O) in response to nasal air
      jet stimulation applied alternately to the nares were made in both active sleep
      (AS) and quiet sleep (QS) while infants slept supine. Arousal thresholds and
      sleep period lengths were compared between formula fed and breast fed infants at
      each age. RESULTS: Arousal thresholds were not different between breast fed and
      formula fed infants in QS. However, in AS breast fed infants were significantly
      more arousable than formula fed infants at 2-3 months of age. There was no
      difference between groups of infants when sleep period length was compared at any
      study. CONCLUSIONS: Breast fed infants are more easily aroused from AS at 2-3
      months of age than formula fed infants. This age coincides with the peak
      incidence of SIDS.

PMID- 14709497
TI  - Trends in paediatric health economic evaluation: 1980 to 1999.
AB  - BACKGROUND: Although standard methods for conducting economic evaluations have
      evolved, little attention has been paid to their application in paediatrics. The
      Paediatric Economic Database Evaluation (PEDE) Project was conceived to promote
      research into paediatric health economic methods. AIM: To examine trends in
      paediatric economic evaluation between 1980 and 1999. METHODS: A comprehensive
      literature database created for the PEDE project was the source of the data.
      Descriptive statistics were used to summarise trends. Publication volume, study
      outcome category, analytical technique, and journal type were examined over the
      study period. RESULTS: The literature search resulted in 787 full paediatric
      economic evaluations. The volume of publications increased from 61 to 440
      citations per 5 year period. The most common health outcome category was cases of
      disease/condition/abnormality. Cost-effectiveness analysis (CEA) was the most
      common technique used, accounting for a majority of evaluations in all time
      periods. The proportion of studies using CEA increased by 23 percentage points,
      while the proportion using cost-benefit analysis decreased from 31% in 1980-84 to
      12% in 1995-99. Cost-utility analysis was the least common analytical technique.
      Publication in journals of paediatrics/perinatal medicine was the most common
      venue for all intervals and increased as a proportion of the total over time.
      CONCLUSIONS: The growth in publication of paediatric economic evaluations
      suggests that increasing attention should be paid to the application of health
      economic methods to a paediatric population to ensure high quality allocation
      decisions.

PMID- 14709498
TI  - Ethnic group differences in overweight and obese children and young people in
      England: cross sectional survey.
AB  - AIMS: To determine the percentage of children and young adults who are obese or
      overweight within different ethnic and socioeconomic groups. METHODS: Secondary
      analysis of data on 5689 children and young adults aged 2-20 years from the 1999
      Health Survey for England. RESULTS: Twenty three per cent of children (n = 1311)
      were overweight, of whom 6% (n = 358) were obese. More girls than boys were
      overweight (24% v 22%). Afro-Caribbean girls were more likely to be overweight
      (odds ratio 1.73, 95% CI 1.29 to 2.33), and Afro-Caribbean and Pakistani girls
      were more likely to be obese than girls in the general population (odds ratios
      2.74 (95% CI 1.74 to 4.31) and 1.71 (95% CI 1.06 to 2.76), respectively). Indian
      and Pakistani boys were more likely to be overweight (odds ratios 1.55 (95% CI
      1.12 to 2.17) and 1.36 (95% CI 1.01 to 1.83), respectively). There were no
      significant differences in the prevalence of obese and overweight children from
      different social classes. CONCLUSION: The percentage of children and young adults
      who are obese and overweight differs by ethnic group and sex, but not by social
      class. British Afro-Caribbean and Pakistani girls have an increased risk of being
      obese and Indian and Pakistani boys have an increased risk of being overweight
      than the general population. These individuals may be at greater combined
      cumulative risk of morbidity and mortality from cardiovascular disease and so may
      be a priority for initiatives to target groups of children at particular risk of
      obesity.

PMID- 14709499
TI  - Soy formula complicates management of congenital hypothyroidism.
AB  - AIMS: To test the hypothesis that feeding soy formula to infants with congenital
      hypothyroidism (CH) leads to prolonged increase of thyroid stimulating hormone
      (TSH). METHODS: The study was a review of 78 patients seen during their first
      year of life between 1990 and 1998. Data regarding clinical diagnosis, date of
      treatment initiation, TSH, levothyroxine dose, weight, length, and diet
      information from each visit were collected from the charts. RESULTS: There were
      eight patients in the soy diet group and 70 in the non-soy diet group. There was
      no significant difference between the two groups in the starting dose of
      levothyroxine or the change in this dose over one year. There was a significant
      difference between the two groups in the following areas: time to TSH
      normalisation, first TSH on treatment, percentage with increased TSH at 4 months
      of age, percentage with increased TSH throughout the first year of life, and in
      the overall trend of TSH at each visit. CONCLUSIONS: Infants fed soy formula had
      prolonged increase of TSH when compared to infants fed non-soy formula. These
      infants need close monitoring of free thyroxine and TSH measurements, and they
      may need increased levothyroxine doses to achieve normal thyroid function tests.

PMID- 14709502
TI  - Progressive fibrosis of the quadriceps muscle.

PMID- 14709501
TI  - Greek adolescents, fitness, fatness, fat intake, activity, and coronary heart
      disease risk.
AB  - BACKGROUND: A dramatic increase in adult mortality rates from coronary heart
      disease (CHD) in Greece, accompanied by increased prevalence of CHD risk factors
      in children, has been documented. However, there is controversy about the
      independent effects of certain lifestyle parameters on primary CHD risk factors.
      AIMS AND METHODS: To examine the association between CHD risk factors (HDL-C, LDL
      C, HDL-C/TC, triglycerides, systolic and diastolic blood pressure) and lifestyle
      parameters (fitness, fatness, fat intake, and physical activity) in 210 12-year
      old Greek pupils. RESULTS: Correcting for the fixed factors of gender and
      maturation, analyses of covariance (ANCOVA) with backward elimination of the
      lifestyle covariates revealed significant associations between three CHD risk
      factors (HDL-C, HDL-C/TC, systolic blood pressure) and physical activity levels.
      In contrast, the covariates aerobic fitness, fatness and fat intake failed to
      reach significance with any of the CHD risk factors. CONCLUSIONS: In Greek
      schoolchildren, primary CHD risk factors are mainly associated with physical
      activity levels, independently of fitness, fatness, and/or fat intake. Prevention
      strategies should concentrate on enhancing physical activity early in life, if
      the increased prevalence of Greek adult CHD mortality is to be diminished.

PMID- 14709503
TI  - Prevalence of tic disorders among primary school students in the city of Pavia,
      Italy.
AB  - BACKGROUND: The prevalence of tic disorders in children varies from 1% to 29%
      depending on the characteristics of the study population, the diagnostic
      criteria, and the study design and methods. AIMS: To calculate the prevalence of
      tic disorders among primary school children in Italy. METHODS: The study
      population comprised 2347 primary school children from the city of Pavia (pop. 80
      073), Northern Italy. Using trained school teachers as the source of cases, all
      children with motor or vocal tics occurring intermittently and unpredictably out
      of a background of normal motor activity were accepted. The type, frequency, and
      circumstances of tic disorders were noted. School performance was correlated to
      the presence of tics. RESULTS: A total of 68 children (56 boys, 12 girls) aged 6
      11 years were identified with tic disorders. The period prevalence was 2.9% (95%
      CI 2.3 to 3.7). The prevalence was 4.4% in boys and 1.1% in girls, with no
      detectable trends at age 6-11. Motor tics were present in 46 cases, vocal tics in
      6, and motor and vocal tics in 16. Situation related tics were noted in 37 cases.
      A significant correlation was found between the presence of tic disorders and
      impaired school performance. DISCUSSIONS: Tic disorders are a fairly uncommon but
      disabling clinical disorder among primary school children from an urban
      community. The fairly low prevalence of this clinical condition, as compared to
      other reports, can be explained by the choice of stringent diagnostic criteria
      and the exclusion of patients with other movement disorders.

PMID- 14709504
TI  - Ethnic differences in the rates of BCG vaccination.
AB  - An audit of the selective neonatal BCG immunisation programme showed that only
      51% of eligible infants received the vaccination. Infants of Indian
      subcontinental origin (ISC) were significantly more likely to have been
      vaccinated than non-ISC infants (ISC 70% v non-ISC 29%). Greater awareness of the
      eligibility of non-ISC infants for BCG as well as simplification of the
      eligibility criteria are needed to help increase BCG vaccination rates.

PMID- 14709505
TI  - Nasal/buccal midazolam use in the community.
AB  - A telephone survey was carried out to evaluate the effectiveness and convenience
      of nasal/buccal midazolam in terminating prolonged seizures in the community. A
      total of 33/40 (83%) families who had used it found it effective and easy to use;
      20/24 (83%) preferred using midazolam to rectal diazepam.

PMID- 14709507
TI  - The progression of maternal RSV antibodies in the offspring.
AB  - The concentrations of maternal anti-RSV IgG antibodies were followed in 49
      healthy newborns over the first six months of life. At birth, 41 mothers (83%)
      tested positive for anti-RSV IgG and all of their babies carried maternal anti
      RSV IgG. Anti-RSV IgG positivity dropped to 73% at 1 month, 6% at 3 months, and
      2% at 6 months. Between 3 and 6 months, 8% did acquire RSV infection, half of
      them as acute bronchiolitis and half as non-specific respiratory infection. All
      of the patients who acquired clinical RSV disease had an antibody concentration
      of <20 RU/ml which may be the cut off value for protection.

PMID- 14709508
TI  - International parallels in leukaemia and diabetes epidemiology.
AB  - Acute lymphoblastic leukaemia (ALL) and type 1 diabetes have an environmental
      aetiology and common epidemiological features. Incidence rates and national
      characteristics of both conditions were investigated in 40 countries worldwide.
      There was a significant positive correlation between diseases. Markers of wealth
      and affluence were significantly associated with high incidence.

PMID- 14709509
TI  - NHS Direct: virtually engaged.
AB  - In the five years since its launch in March 1998, NHS Direct in England and Wales
      has established itself as the world's largest provider of telephone healthcare
      advice. NHS Direct now handles over half a million telephone calls and NHS Direct
      Online half a million on-line transactions every month. Consistently 30-40% of
      calls to the telephone service are about children.

PMID- 14709511
TI  - Pacemaker twiddling.

PMID- 14709510
TI  - The effect of asthma and its treatment on growth.
AB  - Asthma has little, if any, significant effect on attained adult height. Untreated
      asthma results in a delay of puberty by approximately 1.3 years, and pubertal
      delay is likely to explain the majority of apparent growth failure in asthmatics.
      All currently available inhaled corticosteroids (ICS) result in growth
      suppression at conventional doses (400 microg/day of beclomethasone dipropionate
      equivalent), but the growth suppressive effects are relatively short lived, after
      which growth reverts to pretreatment levels. Younger, prepubertal children,
      appear more sensitive to the growth suppressive effects of ICS. Asthmatic
      children receiving conventional doses of ICS (400 microg/day of BDP equivalent)
      will attain an adult height indistinguishable from their predicted adult height
      (based on their mid parental height), and no different from non-asthmatics. Adult
      height could possibly be decreased in severe asthmatics, but this is unlikely to
      be greater than a 1.2 cm decrement. Recent longitudinal studies offer reassurance
      that at conventional doses ICS do not have significant long term effects on
      growth, and that their benefits consistently outweigh their side effects.

PMID- 14709512
TI  - Pitfalls in the assessment of body composition in survivors of acute
      lymphoblastic leukaemia.
AB  - BACKGROUND: Body fat mass (FM) and fat free mass (FFM) in childhood are often
      estimated by conversion of a measured variable into compartmental body
      composition using constants or regression equations that have been previously
      derived in healthy individuals. Application of such constants or equations to
      children with disease states may lead to inappropriate conclusions since the
      "normal" relationships may become altered. AIMS AND METHODS: To test this
      hypothesis by taking measurements of body composition using dual energy x ray
      absorptiometry (DEXA) as a "gold standard" method and calculating hydration and
      body potassium constants using isotopic water dilution and whole body potassium
      counting. Measurements of bioelectrical impedance (BIA) by two different
      analysers (RJL and Holtain) were also performed to allow comparison with body
      water measurements. RESULTS: Measurements were performed in 35 children treated
      for acute lymphoblastic leukaemia (ALL) and compared to those in 21 children
      treated for a variety of other malignancies and 32 healthy sibling controls. The
      mean hydration and potassium content of FFM was significantly reduced in the ALL
      group compared to both other malignancies and controls. Application of equations
      derived from controls for the measurement of FFM derived from bioelectrical
      impedance led to an underestimation of 1.15 kg when compared to that derived from
      DEXA in children treated for ALL but not in other malignancies. For all groups
      combined, BIA was significantly different in the two analysers. CONCLUSION: Care
      needs to be taken in the application of equations derived from the normal
      population to body composition measurement in children treated for ALL.

PMID- 14709513
TI  - Performance of blood tests in diagnosis of inflammatory bowel disease in a
      specialist clinic.
AB  - AIMS: To determine the reliability of a panel of blood tests in screening for
      ulcerative colitis and Crohn's disease. METHODS: The subjects were 153 children
      referred to a paediatric gastroenterology department with possible inflammatory
      bowel disease (IBD). Of these, 103 were found to have IBD (Crohn's disease 60,
      ulcerative colitis 37, indeterminate colitis 6). The 50 without IBD formed the
      controls. Blood tests evaluated included haemoglobin, platelet count, ESR, CRP,
      and albumin. Receiver operating characteristic curves were used where possible to
      determine optimal threshold values. Binary logistic regression analysis was used
      to investigate the five screening tests in combination, and a stepwise method was
      used to find the best test combination. RESULTS: The optimal screening strategy
      used a combination of haemoglobin and platelet count and "1 of 2 abnormal" as the
      criterion for positivity. This was associated with a sensitivity of 90.8% (95% CI
      83.3 to 95.7%), a specificity of 80.0% (95% CI 65.7 to 89.8%), and positive and
      negative predictive values of 94.4% and 75.9% respectively. CONCLUSIONS:
      Haemoglobin and platelet count provide a useful screening test combination for
      patients with suspected IBD. These tests are not completely reliable however. If
      clinical suspicion is high further investigations are required.

PMID- 14709514
TI  - A randomised crossover trial of facemask efficacy.
AB  - The efficacy of different facemasks that can be used in the delivery of aerosol
      medication to children with recurrent wheeze or asthma was investigated. The
      results showed a statistically significant difference between some of the masks
      used, which has important implications for current clinical practice

PMID- 14709515
TI  - Fusidic acid resistance in Staphylococcus aureus.
AB  - This review summarises current knowledge of the microbiological and clinical
      aspects of fusidic acid resistance in Staphylococcus aureus, and makes
      recommendations about fusidic acid prescribing and further research.

PMID- 14709516
TI  - End stage renal disease due to bilateral renal malakoplakia.
AB  - Malakoplakia typically affects the bladders of immunocompromised adults who have
      defective intracellular killing of Escherichia coli. Renal malakoplakia is rare
      in children and generally has a good outcome. In the case presented, however, it
      caused end stage renal failure in a 5 year old girl. The management dilemmas
      surrounding renal transplantation are highlighted.

PMID- 14709520
TI  - Does early administration of dexamethasone improve neurological outcome in
      children with meningococcal meningitis?

PMID- 14709521
TI  - Should nifedipine be used to counter low blood sugar levels in children with
      persistent hyperinsulinaemic hypoglycaemia?

PMID- 14709522
TI  - Do steroids help children with acute urticaria?

PMID- 14709524
TI  - Fever phobia revisited.

PMID- 14709525
TI  - Miconazole and clobazam; a useful interaction in Dravet's syndrome?

PMID- 14709526
TI  - RCPCH guideline appraisal on EEG after first seizure.

PMID- 14709527
TI  - Juvenile myasthenia gravis mimicking recurrent VI nerve palsy of childhood.

PMID- 14709528
TI  - Severe vitamin D deficient rickets in black Afro-Caribbean children.

PMID- 14709529
TI  - Voiding dysfunction in Duchenne muscular dystrophy.

PMID- 14709530
TI  - Hyperchloraemic acidosis consistent with ammonium chloride administration.

PMID- 14709531
TI  - Prevention of hyponatraemia.

PMID- 14709532
TI  - Miliaria crystallina complicating staphylococcal scalded skin syndrome.

PMID- 14709538
TI  - Nuclear stress granules: the awakening of a sleeping beauty?
AB  - Nuclear stress granules are subnuclear compartments that form in response to heat
      shock and other stress stimuli. Although many components of nuclear stress
      granules have been identified, including HSF1 and pre-mRNA processing factors,
      their function remains a mystery. A paper in this issue describes the stress
      induced transcriptional activation of one of the nuclear stress granule target
      sites, a heterochromatic region that has been considered silent (Jolly et al.,
      2004). These intriguing findings will certainly give the research of these
      structures a new twist.

PMID- 14709539
TI  - Trafficking of plasmepsin II to the food vacuole of the malaria parasite
      Plasmodium falciparum.
AB  - A family of aspartic proteases, the plasmepsins (PMs), plays a key role in the
      degradation of hemoglobin in the Plasmodium falciparum food vacuole. To study the
      trafficking of proPM II, we have modified the chromosomal PM II gene in P.
      falciparum to encode a proPM II-GFP chimera. By taking advantage of green
      fluorescent protein fluorescence in live parasites, the ultrastructural
      resolution of immunoelectron microscopy, and inhibitors of trafficking and PM
      maturation, we have investigated the biosynthetic path leading to mature PM II in
      the food vacuole. Our data support a model whereby proPM II is transported
      through the secretory system to cytostomal vacuoles and then is carried along
      with its substrate hemoglobin to the food vacuole where it is proteolytically
      processed to mature PM II.

PMID- 14709540
TI  - PEX19 is a predominantly cytosolic chaperone and import receptor for class 1
      peroxisomal membrane proteins.
AB  - Integral peroxisomal membrane proteins (PMPs) are synthesized in the cytoplasm
      and imported posttranslationally. Here, we demonstrate that PEX19 binds and
      stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting
      signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals,
      and is essential for PMP targeting and import. These results show that PEX19
      functions as both a chaperone and an import receptor for newly synthesized PMPs.
      We also demonstrate the existence of two PMP import mechanisms and two classes of
      mPTSs: class 1 mPTSs, which are bound by PEX19 and imported in a PEX19-dependent
      manner, and class 2 mPTSs, which are not bound by PEX19 and mediate protein
      import independently of PEX19.

PMID- 14709541
TI  - Role of the hydrophobic domain in targeting caveolin-1 to lipid droplets.
AB  - Although caveolins normally reside in caveolae, they can accumulate on the
      surface of cytoplasmic lipid droplets (LDs). Here, we first provided support for
      our model that overaccumulation of caveolins in the endoplasmic reticulum (ER)
      diverts the proteins to nascent LDs budding from the ER. Next, we found that a
      mutant H-Ras, present on the cytoplasmic surface of the ER but lacking a
      hydrophobic peptide domain, did not accumulate on LDs. We used the fact that wild
      type caveolin-1 accumulates in LDs after brefeldin A treatment or when linked to
      an ER retrieval motif to search for mutants defective in LD targeting. The
      hydrophobic domain, but no specific sequence therein, was required for LD
      targeting of caveolin-1. Certain Leu insertions blocked LD targeting,
      independently of hydrophobic domain length, but dependent on their position in
      the domain. We propose that proper packing of putative hydrophobic helices may be
      required for LD targeting of caveolin-1.

PMID- 14709542
TI  - Apaf-1 and caspase-9 do not act as tumor suppressors in myc-induced
      lymphomagenesis or mouse embryo fibroblast transformation.
AB  - Based on experiments with cultured fibroblasts, the apoptosis regulators caspase
      9 and Apaf-1 are hypothesized to function as tumor suppressors. To investigate
      their in vivo role in lymphomagenesis, an IgH enhancer-driven c-myc transgene was
      crossed onto Apaf-1(-/-) and caspase-9(-/-) mice. Due to perinatal lethality, Emu
      myc transgenic Apaf-1(-/-) or caspase-9(-/-) fetal liver cells were used to
      reconstitute lethally irradiated recipient mice. Surprisingly, no differences
      were seen in rate, incidence, or severity of lymphoma with loss of Apaf-1 or
      caspase-9, and Apaf-1 was not a critical determinant of anticancer drug
      sensitivity of c-myc-induced lymphomas. Moreover, loss of Apaf-1 did not promote
      oncogene-induced transformation of mouse embryo fibroblasts. Thus, Apaf-1 and
      caspase-9 do not suppress c-myc-induced lymphomagenesis and embryo fibroblast
      transformation.

PMID- 14709543
TI  - Oriented clonal cell growth in the developing mouse myocardium underlies cardiac
      morphogenesis.
AB  - During heart morphogenesis, cardiac chambers arise by differential expansion of
      regions of the primitive cardiac tube. This process is under the control of
      specific transcription factors such as Tbx5 and dHAND. To gain insight into the
      cellular mechanisms that underlie cardiogenesis, we have used a retrospective
      clonal approach based on the spontaneous recombination of an nlaacZ reporter gene
      targeted to the murine alpha-cardiac actin locus. We show that clonal growth of
      myocardial cells is oriented. At embryonic day (E) 10.5, the shape of clones is
      characteristic of a given cardiac region and reflects its morphology. This is
      already detectable in the primitive cardiac tube at E8.5, and is maintained after
      septation at E14.5 with additional modulations. The clonal analysis reveals new
      subdivisions of the myocardium, including an interventricular boundary region.
      Our results show that the myocardium, from the time of its formation, is a
      polarized and regionalized tissue and point to the role of oriented clonal cell
      growth in cardiac chamber morphogenesis.

PMID- 14709544
TI  - IGF-I instructs multipotent adult neural progenitor cells to become
      oligodendrocytes.
AB  - Adult multipotent neural progenitor cells can differentiate into neurons,
      astrocytes, and oligodendrocytes in the mammalian central nervous system, but the
      molecular mechanisms that control their differentiation are not yet well
      understood. Insulin-like growth factor I (IGF-I) can promote the differentiation
      of cells already committed to an oligodendroglial lineage during development.
      However, it is unclear whether IGF-I affects multipotent neural progenitor cells.
      Here, we show that IGF-I stimulates the differentiation of multipotent adult rat
      hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling
      analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte
      differentiation by IGF-I appears to be mediated through an inhibition of bone
      morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the
      hippocampus leads to an increase in oligodendrocyte markers. These data
      demonstrate the existence of a single molecule, IGF-I, that can influence the
      fate choice of multipotent adult neural progenitor cells to an oligodendroglial
      lineage.

PMID- 14709545
TI  - Amyloid-beta peptide induces oligodendrocyte death by activating the neutral
      sphingomyelinase-ceramide pathway.
AB  - Amyloid-beta peptide (Abeta) accumulation in senile plaques, a pathological
      hallmark of Alzheimer's disease (AD), has been implicated in neuronal
      degeneration. We have recently demonstrated that Abeta induced oligodendrocyte
      (OLG) apoptosis, suggesting a role in white matter pathology in AD. Here, we
      explore the molecular mechanisms involved in Abeta-induced OLG death, examining
      the potential role of ceramide, a known apoptogenic mediator. Both Abeta and
      ceramide induced OLG death. In addition, Abeta activated neutral sphingomyelinase
      (nSMase), but not acidic sphingomyelinase, resulting in increased ceramide
      generation. Blocking ceramide degradation with N-oleoyl-ethanolamine exacerbated
      Abeta cytotoxicity; and addition of bacterial sphingomyelinase (mimicking
      cellular nSMase activity) induced OLG death. Furthermore, nSMase inhibition by 3
      O-methyl-sphingomyelin or by gene knockdown using antisense oligonucleotides
      attenuated Abeta-induced OLG death. Glutathione (GSH) precursors inhibited Abeta
      activation of nSMase and prevented OLG death, whereas GSH depletors increased
      nSMase activity and Abeta-induced death. These results suggest that Abeta induces
      OLG death by activating the nSMase-ceramide cascade via an oxidative mechanism.

PMID- 14709546
TI  - Microdomains of the C-type lectin DC-SIGN are portals for virus entry into
      dendritic cells.
AB  - The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule
      grabbing non-integrin (DC-SIGN; CD209) facilitates binding and internalization of
      several viruses, including HIV-1, on DCs, but the underlying mechanism for being
      such an efficient phagocytic pathogen-recognition receptor is poorly understood.
      By high resolution electron microscopy, we demonstrate a direct relation between
      DC-SIGN function as viral receptor and its microlocalization on the plasma
      membrane. During development of human monocyte-derived DCs, DC-SIGN becomes
      organized in well-defined microdomains, with an average diameter of 200 nm.
      Biochemical experiments and confocal microscopy indicate that DC-SIGN
      microdomains reside within lipid rafts. Finally, we show that the organization of
      DC-SIGN in microdomains on the plasma membrane is important for binding and
      internalization of virus particles, suggesting that these multimolecular
      assemblies of DC-SIGN act as a docking site for pathogens like HIV-1 to invade
      the host.

PMID- 14709547
TI  - Glial lipoproteins stimulate axon growth of central nervous system neurons in
      compartmented cultures.
AB  - The role of lipoproteins secreted by cortical glial cells in axon growth of
      central nervous system (CNS) neurons was investigated. We first established
      compartmented cultures of CNS neurons (retinal ganglion cells). Addition of glial
      cell-conditioned medium (GCM) to distal axons increased the rate of axon
      extension by approximately 50%. Inhibition of 3-hydroxy-3-methylglutaryl-CoA
      reductase in glial cells diminished the secretion of cholesterol and
      apolipoprotein E, and prevented the growth stimulatory effect of GCM. When glia
      derived lipoproteins containing apolipoprotein E were provided to distal axons,
      axon extension was stimulated to the same extent as by GCM. In contrast, addition
      of lipoproteins to cell bodies failed to enhance growth. The growth stimulatory
      effect of glial lipoproteins was abrogated in the presence of receptor-associated
      protein, RAP, indicating involvement of receptor(s) of the low density
      lipoprotein receptor family in stimulation of axonal extension. These
      observations suggest that glial cells stimulate axon growth of CNS neurons by
      providing lipoproteins containing cholesterol and apolipoprotein E to distal
      axons.

PMID- 14709548
TI  - Lassa virus glycoprotein signal peptide displays a novel topology with an
      extended endoplasmic reticulum luminal region.
AB  - Lassa virus glycoprotein C (GP-C) is translated as a precursor (preGP-C) into the
      lumen of the endoplasmic reticulum (ER) and cotranslationally cleaved into the
      signal peptide and immature GP-C before GP-C is proteolytically processed into
      its subunits, GP-1 and GP-2, which form the mature virion spikes. The signal
      peptide of preGP-C comprises 58 amino acids and contains two distinct hydrophobic
      domains. Here, we show that each hydrophobic domain alone can insert preGP-C into
      the ER membrane. Furthermore, we demonstrate that the native signal peptide only
      uses the N-terminal hydrophobic domain for membrane insertion, exhibiting a novel
      type of a topology for signal peptides with an extended ER luminal part, which is
      essential for proteolytic processing of GP-C into GP-1 and GP-2.

PMID- 14709549
TI  - Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA
      receptor trafficking via the GDI.Rab5 complex. Potential role in (S)-3,5
      dihydroxyphenylglycene-induced long term depression.
AB  - Recent evidence has emphasized the importance of p38 mitogen-activated protein
      kinase (MAPK) in the induction of metabotropic glutamate receptor (mGluR)
      dependent long term depression (LTD) at hippocampal CA3-CA1 synapses. However,
      the cascade responsible of mGluR to activate p38 MAPK and the signaling pathway
      immediately downstream from it to induce synaptic depression is poorly
      understood. Here, we show that transient activation of group I mGluR with the
      selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) activates p38 MAPK
      through G protein betagamma-subunit, small GTPase Rap1, and MAPK kinase 3/6
      (MKK3/6), thus resulting in mGluR5-dependent LTD. Furthermore, our data clearly
      show that an accelerating AMPA receptor endocytosis by stimulating the formation
      of guanyl nucleotide dissociation inhibitor-Rab5 complex is a potential
      downstream processing of p38 MAPK activation to mediate DHPG-LTD. These results
      suggest an important role for Rap1-MKK3/6-p38 MAPK pathway in the induction of
      mGluR-dependent LTD by directly coupling to receptor trafficking machineries to
      facilitate the loss of synaptic AMPA receptors.

PMID- 14709550
TI  - A new group of antifungal and antibacterial lipopeptides derived from non
      membrane active peptides conjugated to palmitic acid.
AB  - We report on the synthesis, biological function, and a plausible mode of action
      of a new group of lipopeptides with potent antifungal and antibacterial
      activities. These lipopeptides are derived from positively charged peptides
      containing d- and l-amino acids (diastereomers) that are palmitoylated (PA) at
      their N terminus. The peptides investigated have the sequence K(4)X(7)W, where X
      designates Gly, Ala, Val, or Leu (designated d-X peptides). The data revealed
      that PA-d-G and PA-d-A gained potent antibacterial and antifungal activity
      despite the fact that both parental peptides were completely devoid of any
      activity toward microorganisms and model phospholipid membranes. In contrast, PA
      d-L lost the potent antibacterial activity of the parental peptide but gained and
      preserved partial antifungal activity. Interestingly, both d-V and its
      palmitoylated analog were inactive toward bacteria, and only the palmitoylated
      peptide was highly potent toward yeast. Both PA-d-L and PA-d-V lipopeptides were
      also endowed with hemolytic activity. Mode of action studies were performed by
      using tryptophan fluorescence and attenuated total reflectance Fourier transform
      infrared and circular dichroism spectroscopy as well as transmembrane
      depolarization assays with bacteria and fungi. The data suggest that the
      lipopeptides act by increasing the permeability of the cell membrane and that
      differences in their potency and target specificity are the result of differences
      in their oligomeric state and ability to dissociate and insert into the
      cytoplasmic membrane. These results provide insight regarding a new approach of
      modulating hydrophobicity and the self-assembly of non-membrane interacting
      peptides in order to endow them with both antibacterial and antifungal activities
      urgently needed to combat bacterial and fungal infections.

PMID- 14709551
TI  - The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase
      dependent survival signaling cascade.
AB  - Hepatitis C virus (HCV) establishes a persistent infection, with up to 80% of
      infected individuals proceeding to chronic hepatitis, which in many cases may
      result in liver cirrhosis and hepatocellular carcinoma (HCC); indeed HCV
      infection is increasingly associated with the development of HCC. The long time
      period (up to 30 years) between primary infection and the onset of HCC implies
      that HCV is not directly oncogenic but in some way predisposes patients to
      develop tumors, though the mechanism for this is unclear as yet. We report here
      that NS5A binds directly to the Src homology 3 domain of the p85 regulatory
      subunit of phosphoinositide 3-kinase (PI3K), and this interaction is mediated by
      a novel (non-proline-rich) motif within NS5A. Coimmunoprecipitation analysis
      revealed that NS5A bound native heterodimeric PI3K and enhanced the
      phosphotransferase activity of the catalytic (p110) subunit both in vitro and in
      human cell lines harboring a subgenomic HCV replicon or expressing NS5A alone.
      NS5A-mediated activation of PI3K resulted in increased phosphorylation and
      activity of Akt/protein kinase B and concomitantly provided protection against
      the induction of apoptosis in both replicon-harboring cells and cells stably
      expressing NS5A alone. These data suggest that stimulation of PI3K by NS5A may
      represent an indirect mechanism for development of HCC in HCV-infected patients
      and further suggests potential therapeutic strategies to counteract the
      occurrence of HCV-related HCC.

PMID- 14709552
TI  - Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta
      amyloid peptide production and alters lymphopoiesis and intestinal cell
      differentiation.
AB  - Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of
      the amyloid precursor protein (APP) to produce the pathogenic beta-amyloid
      (Abeta) peptides, is an attractive approach to the treatment of Alzheimer
      disease. In addition to APP, however, several other gamma-secretase substrates
      have been identified (e.g. Notch), and altered processing of these substrates by
      gamma-secretase inhibitors could lead to unintended biological consequences. To
      study the in vivo consequences of gamma-secretase inhibition, the gamma-secretase
      inhibitor LY-411,575 was administered to C57BL/6 and TgCRND8 APP transgenic mice
      for 15 days. Although most tissues were unaffected, doses of LY-411,575 that
      inhibited Abeta production had marked effects on lymphocyte development and on
      the intestine. LY-411,575 decreased overall thymic cellularity and impaired
      intrathymic differentiation at the CD4(-)CD8(-)CD44(+)CD25(+) precursor stage. No
      effects on peripheral T cell populations were noted following LY-411,575
      treatment, but evidence for the altered maturation of peripheral B cells was
      observed. In the intestine, LY-411,575 treatment increased goblet cell number and
      drastically altered tissue morphology. These effects of LY-411,575 were not seen
      in mice that were administered LY-D, a diastereoisomer of LY-411,575, which is a
      very weak gamma-secretase inhibitor. These studies show that inhibition of gamma
      secretase has the expected benefit of reducing Abeta in a murine model of
      Alzheimer disease but has potentially undesirable biological effects as well,
      most likely because of the inhibition of Notch processing.

PMID- 14709553
TI  - Binding of copper(I) by the Wilson disease protein and its copper chaperone.
AB  - The Wilson disease protein (WND) is a transport ATPase involved in copper
      delivery to the secretory pathway. Mutations in WND and its homolog, the Menkes
      protein, lead to genetic disorders of copper metabolism. The WND and Menkes
      proteins are distinguished from other P-type ATPases by the presence of six
      soluble N-terminal metal-binding domains containing a conserved CXXC metal
      binding motif. The exact roles of these domains are not well established, but
      possible functions include exchanging copper with the metallochaperone Atox1 and
      mediating copper-responsive cellular relocalization. Although all six domains can
      bind copper, genetic and biochemical studies indicate that the domains are not
      functionally equivalent. One way the domains could be tuned to perform different
      functions is by having different affinities for Cu(I). We have used isothermal
      titration calorimetry to measure the association constant (K(a)) and
      stoichiometry (n) values of Cu(I) binding to the WND metal-binding domains and to
      their metallochaperone Atox1. The association constants for both the chaperone
      and target domains are approximately 10(5) to 10(6) m(-1), suggesting that the
      handling of copper by Atox1 and copper transfer between Atox1 and WND are under
      kinetic rather than thermodynamic control. Although some differences in both n
      and K(a) values are observed for variant proteins containing less than the full
      complement of six metal-binding domains, the data for domains 1-6 were best
      fitted with a single site model. Thus, the individual functions of the six WND
      metal-binding domains are not conferred by different Cu(I) affinities but instead
      by fold and electrostatic surface properties.

PMID- 14709554
TI  - Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an
      evolutionarily conserved motif and is sensitive to inositol hexakisphosphate.
AB  - Synaptotagmins are membrane proteins that possess tandem C2 domains and play an
      important role in regulated membrane fusion in metazoan organisms. Here we show
      that both synaptotagmins I and II, the two major neuronal isoforms, can interact
      with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the
      immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion
      complex. A stretch of basic amino acids highly conserved throughout the animal
      kingdom is responsible for this calcium-independent interaction. Inositol
      hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer,
      which is mirrored by changes in chromaffin cell exocytosis. Our results shed new
      light on the functional importance of the conserved polybasic synaptotagmin
      motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up
      regulate the probability of SNARE-mediated membrane fusion.

PMID- 14709555
TI  - Purification and cloning of an endogenous protein inhibitor of carp nephrosin, an
      astacin metalloproteinase.
AB  - Nephrosin is a newly discovered member of the astacin family. It is a secreted
      proteinase and is present in carp head kidney, kidney, and spleen, all of which
      are responsible for immune and hematopoietic functions in fish. A complex formed
      by nephrosin and its inhibitor was purified from carp kidney extract by heparin
      affinity column chromatography. The presence of the nephrosin-inhibitor complex
      in different tissues was examined by immunoblotting with polyclonal antisera
      against the purified nephrosin inhibitor and nephrosin. Both nephrosin and the
      nephrosin inhibitor were present mainly in gill, head kidney, kidney, and spleen.
      In addition, we have cloned the cDNA encoding the nephrosin inhibitor. There are
      two different cDNA clones possibly resulting from two different genes, and the
      long form contains unique tandem repeat sequences in the 3'-end. The deduced
      primary structure of nephrosin inhibitor is similar to that of fetuin-A, a
      mammalian protein present in blood, liver, cerebrospinal fluid, and cerebral
      cortex during fetal development. Treatment with both N-glycosidase F and O
      glycosidase removed the carbohydrate moiety of the nephrosin inhibitor and
      decreased the apparent molecular mass from 40 to 30 kDa. The nephrosin inhibitor
      seems to be synthesized in liver and then secreted to the blood as a precursor.
      When it was distributed into hematopoietic tissues, it was processed from 67 to
      40 kDa and acquired inhibitory activity. This processing phenomenon of fetuin has
      not been reported elsewhere. Importantly, the presence of an endogenous inhibitor
      of nephrosin is the first report of this kind for astacin enzymes. It is very
      likely that endogenous tissue inhibitors may also be present for the regulation
      of other astacin enzymes.

PMID- 14709556
TI  - Isolation of nlz2 and characterization of essential domains in Nlz family
      proteins.
AB  - In this study, we first cloned nlz2, a second zebrafish member of the nlz-related
      zinc-finger gene family. nlz2 was expressed together with nlz1 in a broad
      posterior domain during gastrula stages as well as at the midbrain-hindbrain
      boundary and in the hindbrain caudal to rhombomere 4 during segmentation. nlz2
      was also expressed in regions distinct from nlz1, notably in the forebrain,
      midbrain, and trunk. Misexpression of nlz2 in zebrafish embryos disrupted gene
      expression in the rostral hindbrain, similar to the effect of misexpressing nlz1.
      We next compared the nlz1 and nlz2 sequences to identify and characterize domains
      conserved within this family. We found a C-terminal domain required for nuclear
      localization and two conserved domains (the Sp motif and a putative C(2)H(2) zinc
      finger) required for nlz1 function. We also demonstrate that Nlz1 self-associated
      via its C terminus, interacted with Nlz2, and bound to histone deacetylases.
      Last, we found two forms of Nlz1 generated from alternative translation
      initiation sites in vivo. These forms have distinct activities, apparently
      depending on the function of the N-terminal Sp motif. Our data demonstrate that
      nlz2 functions similarly to nlz1 and define conserved domains essential for
      nuclear localization, self-association, and corepressor binding in this novel
      family of zinc-finger genes.

PMID- 14709557
TI  - Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic
      elongation factor 2 kinase and to its phosphorylation at a novel site, serine
      398.
AB  - Protein synthesis consumes a high proportion of the metabolic energy of mammalian
      cells, and most of this is used by peptide chain elongation. An important
      regulator of energy supply and demand in eukaryotic cells is the AMP-activated
      protein kinase (AMPK). The rate of peptide chain elongation can be modulated
      through the phosphorylation of eukaryotic elongation factor (eEF) 2, which
      inhibits its activity and is catalyzed by a specific calcium/calmodulin-dependent
      protein kinase termed eEF2 kinase. Here we show that AMPK directly phosphorylates
      eEF2 kinase, and we identify the major site of phosphorylation as Ser-398 in a
      regulatory domain of eEF2 kinase. AMPK also phosphorylates two other sites (Ser
      78 and Ser-366) in eEF2 kinase in vitro. We develop appropriate phosphospecific
      antisera and show that phosphorylation of Ser-398 in eEF2 kinase is enhanced in
      intact cells under a range of conditions that activate AMPK and increase the
      phosphorylation of eEF2. Ser-78 and Ser-366 do not appear to be phosphorylated by
      AMPK within cells. Although cardiomyocytes appear to contain a distinct isoform
      of eEF2 kinase, it also contains a site corresponding to Ser-398 that is
      phosphorylated by AMPK in vitro. Stimuli that activate AMPK and increase eEF2
      phosphorylation within cells increase the activity of eEF2 kinase. Thus, AMPK and
      eEF2 kinase may provide a key link between cellular energy status and the
      inhibition of protein synthesis, a major consumer of metabolic energy.

PMID- 14709558
TI  - Autocrine/paracrine secreted Frizzled-related protein 2 induces cellular
      resistance to apoptosis: a possible mechanism of mammary tumorigenesis.
AB  - Abnormal regulation of apoptosis and cell proliferation is thought to be involved
      in tumor formation. The secreted Frizzled-related protein 2 (SFRP2) was detected
      in primary culture of canine mammary gland tumors but not in normal mammary
      tissues. Thus, to elucidate the role of SFRP2 in mammary tumorigenesis, we
      overexpressed SFRP2 in mammary gland tumor and MCF7 cells. The results indicated
      that SFRP2 is secreted and incorporated into the extracellular matrix (ECM) of
      the tumor and normal cells. In an attempt to understand the molecular basis
      underlying the interaction between SFRP2 and ECM, co-immunoprecipitation and cell
      adhesion assays were carried out. SFRP2 was found to be associated with the
      fibronectin-integrin protein complex and could promote cell adhesion. DNA
      fragmentation and caspase 3 activity analyses showed that the susceptibility of
      the cells to UV-induced apoptosis decreased in the context of SFRP2
      overexpression. Upon disruption of the fibronectin-integrin connection, the
      antiapoptosis activity of SFRP2 was decreased. Moreover, SFRP2 was found to
      induce tumorous transformation in normal mammary epithelial cells and to inhibit
      apoptosis in a modified paracrine model. Collectively, our results emphasize the
      relevance of SFRP2 and ECM in mammary tumorigenesis and provide further insight
      into the mechanism of SFRP2 action.

PMID- 14709559
TI  - The effect of cholesterol and monosialoganglioside (GM1) on the release and
      aggregation of amyloid beta-peptide from liposomes prepared from brain membrane
      like lipids.
AB  - In order to investigate the influence of cholesterol (Ch) and
      monosialoganglioside (GM1) on the release and subsequent deposition/aggregation
      of amyloid beta peptide (Abeta)-(1-40) and Abeta-(1-42), we have examined Abeta
      peptide model membrane interactions by circular dichroism, turbidity
      measurements, and transmission electron microscopy (TEM). Model liposomes
      containing Abeta peptide and a lipid mixture composition similar to that found in
      the cerebral cortex membranes (CCM-lipid) have been prepared. In all, four Abeta
      containing liposomes were investigated: CCM-lipid; liposomes with no GM1 (GM1
      free lipid); those with no cholesterol (Ch-free lipid); liposomes with neither
      cholesterol nor GM1 (Ch-GM1-free lipid). In CCM liposomes, Abeta was rapidly
      released from membranes to form a well defined fibril structure. However, for the
      GM1-free lipid, Abeta was first released to yield a fibril structure about the
      membrane surface, then the membrane became disrupted resulting in the formation
      of small vesicles. In Ch-free lipid, a fibril structure with a phospholipid
      membrane-like shadow formed, but this differed from the well defined fibril
      structure seen for CCM-lipid. In Ch-GM1-free lipid, no fibril structure formed,
      possibly because of membrane solubilization by Abeta. The absence of fibril
      structure was noted at physiological extracellular pH (7.4) and also at
      liposomal/endosomal pH (5.5). Our results suggest a possible role for both Ch and
      GM1 in the membrane release of Abeta from brain lipid bilayers.

PMID- 14709560
TI  - Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2,
      cPLA2delta, induced in psoriatic skin.
AB  - Psoriasis is a common skin disease characterized by hyperplastic regenerative
      epidermal growth and infiltration of immunocytes. The etiology of psoriasis is
      unknown, although several genetic and cellular factors have been elucidated. To
      find new psoriasis-related genes, we have cloned cDNAs that are differentially
      expressed between normal and psoriatic skins. Among these clones, we have
      identified a new gene that codes for a new member of the type IV cytosolic
      phospholipase A(2) (cPLA(2)) family. We refer to this gene as cPLA(2)delta. It
      encodes a polypeptide of 818 amino acids that has significant homology with known
      cPLA(2) proteins in the C2 and catalytic domains. The cPLA(2)delta gene was
      mapped to the 15q13-14 chromosomal locus, near to the locus of the cPLA(2)beta
      gene, from which it is separated by a physical distance of about 220 kb. To
      identify the phospholipase A(2) activity of cPLA(2)delta, we transfected COS-7
      cells with His-tagged cPLA(2)delta. The cell lysate from these cells had calcium
      dependent phospholipase A(2) activity. Northern blot analysis revealed that a
      cPLA(2)delta transcript of about 4 kb is expressed in stratified squamous
      epithelia, such as those in skin and cervix, but not in other tissues. In situ
      hybridization and immunohistochemistry revealed that cPLA(2)delta is expressed
      strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly
      and discontinuously in atopic dermatitis and mycosis fungoides, and not detected
      in the epidermis of normal skin; cPLA(2)alpha is not detected in either normal or
      psoriatic skin. These results suggest that cPLA(2)delta exhibits a unique
      distribution pattern compared with that of known cPLA(2) subtypes, and it may
      play a critical role in inflammation in psoriatic lesions.

PMID- 14709561
TI  - A piece of my mind. Winners and losers.

PMID- 14709562
TI  - National autism summit charts a path through a scientific, clinical wilderness.

PMID- 14709563
TI  - Global AIDS epidemic worsens.

PMID- 14709564
TI  - FDA seeks genome-based drug data.

PMID- 14709567
TI  - Efficacy of sertraline in the treatment of children and adolescents with major
      depressive disorder.

PMID- 14709568
TI  - Efficacy of sertraline in the treatment of children and adolescents with major
      depressive disorder.

PMID- 14709569
TI  - Efficacy of sertraline in the treatment of children and adolescents with major
      depressive disorder.

PMID- 14709570
TI  - Efficacy of sertraline in the treatment of children and adolescents with major
      depressive disorder.

PMID- 14709571
TI  - Hormone therapy and risk of gynecologic cancers.

PMID- 14709572
TI  - Magnets for patients with heel pain.

PMID- 14709573
TI  - Changes in prescribing patterns following publication of the ALLHAT trial.

PMID- 14709574
TI  - Relationship between CCR5 density and viral load after discontinuation of
      antiretroviral therapy.

PMID- 14709575
TI  - National use of postmenopausal hormone therapy: annual trends and response to
      recent evidence.
AB  - CONTEXT: Postmenopausal hormone therapy use increased dramatically during the
      past 2 decades because of a prevailing belief in its health benefits. Recent
      evidence from randomized trials published in July 2002 demonstrated adverse
      cardiovascular disease events and other risks with hormone therapy in the form of
      oral estrogen combined with progestin. OBJECTIVE: To describe patterns of hormone
      therapy use from 1995 until July 2003, including the impact of recent evidence.
      DESIGN, SETTING, AND POPULATION: Two databases were used to describe national
      trends in hormone therapy use from January 1995 to July 2003. The National
      Prescription Audit database provided data on the number of hormone therapy
      prescriptions filled by retail pharmacies and the National Disease and
      Therapeutic Index database provided data on patient visits to office-based
      physicians during which hormone therapy was prescribed. MAIN OUTCOME MEASURES:
      Annual number of hormone therapy prescriptions and characteristics of visits to
      physicians during which hormone therapy was prescribed. RESULTS: Annual hormone
      therapy prescriptions increased from 58 million in 1995 to 90 million in 1999,
      representing approximately 15 million women per year, then remained stable
      through June 2002. Adoption of new oral estrogen/progestin combinations,
      primarily Prempro, accounted for most of this growth. Obstetrician/gynecologists
      provided more than 70% of hormone therapy prescriptions, and more than one third
      of patients were older than 60 years. Following the publication of trial results
      in July 2002, hormone therapy prescriptions declined in successive months.
      Relative to January-June 2002, prescriptions from January-June 2003 declined by
      66% for Prempro and 33% for Premarin. Small increases were observed in vaginal
      formulations and in new prescriptions for low-dose Premarin. If prescription
      rates observed through July 2003 remain stable, a decline to 57 million
      prescriptions for 2003, similar to the rate in 1995, is projected. CONCLUSIONS:
      Clinical practice responded rapidly to recent evidence of harms associated with
      hormone therapy. Since July 2002, many patients have discontinued hormone therapy
      or are tapering to lower doses.

PMID- 14709576
TI  - Impact of clinical trial results on national trends in alpha-blocker prescribing,
      1996-2002.
AB  - CONTEXT: Research on factors that influence prescribing patterns and the extent
      of change produced by clinical trial findings is limited. OBJECTIVE: To examine
      the changes in prescribing of alpha-blockers for hypertension treatment before
      and after the April 2000 publication of the unfavorable Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) early termination
      involving the study's doxazosin mesylate arm. Changes in prescribing were
      considered in the context of other potential concurrent influences on medication
      use between 1996 and 2002, including changes in alpha-blocker drug prices,
      generic conversion, drug promotion, and competition. DESIGN, SETTING, AND
      PATIENTS: Using 2 national pharmaceutical market research reports published by
      IMS HEALTH, alpha-blocker prescription orders reported in the National
      Prescription Audit-a random computerized sample of about 20 000 of 29 000 retail,
      independent, and mail order pharmacies and mass merchandise and discount houses-
      and office-based physician alpha-blocker prescribing patterns reported in the
      National Disease and Therapeutic Index--a random stratified sample of about 3500
      physician offices--were tracked. OUTCOME MEASURES: Trends in physician-reported
      use of alpha-blockers and alpha-blocker prescribing and dispensing by US
      pharmacies. RESULTS: There were steady increases in alpha-blocker new
      prescriptions, dispensed prescriptions, and physician drug use from 1996 through
      1999. There was a moderate reversal in these trends following ALLHAT early
      termination and subsequent publications in early 2000. Between 1999 and 2002, new
      annual alpha-blocker prescription orders declined by 26% (from 5.15 million to
      3.79 million), dispensed prescriptions by 22% (from 17.2 million to 13.4
      million), and physician-reported drug use by 54% (from 2.26 million to 1.03
      million). Other potential influences did not appear to have contributed
      significantly to this decline although cessation of alpha-blocker marketing may
      have hastened the decline. CONCLUSIONS: Modest yet statistically significant
      declines in the use of doxazosin and other alpha-blockers coincided with the
      early termination of the ALLHAT doxazosin arm. Although physicians responded to
      this new evidence, strategies to augment the impact of clinical trials on
      clinical practice are warranted.

PMID- 14709577
TI  - Intrathecal ziconotide in the treatment of refractory pain in patients with
      cancer or AIDS: a randomized controlled trial.
AB  - CONTEXT: Ziconotide (formerly SNX-111) selectively blocks N-type voltage
      sensitive calcium channels and may be effective in patients with pain that is
      refractory to opioid therapy or those with intolerable opioid-related adverse
      effects. OBJECTIVE: To assess the safety and efficacy of intrathecal ziconotide
      in patients with pain that is refractory to conventional treatment. DESIGN,
      SETTING, AND PATIENTS: Double-blind, placebo-controlled, randomized trial
      conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the
      United States, Australia, and the Netherlands. Patients were 111 individuals ages
      24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain
      Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a
      2:1 ratio to receive ziconotide or placebo treatment. INTERVENTIONS: Intrathecal
      ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase
      for responders and crossover of nonresponders to the opposite treatment group.
      MAIN OUTCOME MEASURE: Mean percentage change in VASPI score from baseline to the
      end of the initial titration period. RESULTS: Of the evaluable population, 67
      (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving
      placebo were taking opioids at baseline (median morphine equivalent dosage of 300
      mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based
      on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores
      were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group
      (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%
      62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo
      group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase.
      Pain relief was moderate to complete in 52.9% of patients in the ziconotide group
      compared with 17.5% in the placebo group (P<.001). Five patients receiving
      ziconotide achieved complete pain relief, and 50.0% of patients receiving
      ziconotide responded to therapy compared with 17.5% of those receiving placebo (P
      =.001). CONCLUSION: Intrathecal ziconotide provided clinically and statistically
      significant analgesia in patients with pain from cancer or AIDS.

PMID- 14709578
TI  - Enthusiasm for cancer screening in the United States.
AB  - CONTEXT: Public health officials, physicians, and disease advocacy groups have
      worked hard to educate individuals living in the United States about the
      importance of cancer screening. OBJECTIVE: To determine the public's enthusiasm
      for early cancer detection. DESIGN, SETTING, AND PARTICIPANTS: Survey using a
      national telephone interview of adults selected by random digit dialing,
      conducted from December 2001 through July 2002. Five hundred individuals
      participated (women aged > or =40 years and men aged > or =50 years; without a
      history of cancer). MAIN OUTCOME MEASURES: Responses to a survey with 5 modules:
      a general screening module (eg, value of early detection, total-body computed
      tomography); and 4 screening test modules: Papanicolaou test; mammography;
      prostate-specific antigen (PSA) test; and sigmoidoscopy or colonoscopy. RESULTS:
      Most adults (87%) believe routine cancer screening is almost always a good idea
      and that finding cancer early saves lives (74% said most or all the time). Less
      than one third believe that there will be a time when they will stop undergoing
      routine screening. A substantial proportion believe that an 80-year-old who chose
      not to be tested was irresponsible: ranging from 41% with regard to mammography
      to 32% for colonoscopy. Thirty-eight percent of respondents had experienced at
      least 1 false-positive screening test; more than 40% of these individuals
      characterized that experience as "very scary" or the "scariest time of my life."
      Yet, looking back, 98% were glad they had had the initial screening test. Most
      had a strong desire to know about the presence of cancer regardless of its
      implications: two thirds said they would want to be tested for cancer even if
      nothing could be done; and 56% said they would want to be tested for what is
      sometimes termed pseudodisease (cancers growing so slowly that they would never
      cause problems during the persons lifetime even if untreated). Seventy-three
      percent of respondents would prefer to receive a total-body computed tomographic
      scan instead of receiving 1000 dollars in cash. CONCLUSIONS: The public is
      enthusiastic about cancer screening. This commitment is not dampened by false
      positive test results or the possibility that testing could lead to unnecessary
      treatment. This enthusiasm creates an environment ripe for the premature
      diffusion of technologies such as total-body computed tomographic scanning,
      placing the public at risk of overtesting and overtreatment.

PMID- 14709579
TI  - Surgical site infection and the routine use of perioperative hyperoxia in a
      general surgical population: a randomized controlled trial.
AB  - CONTEXT: Surgical site infection (SSI) in the general surgical population is a
      significant public health issue. The use of a high fractional inspired
      concentration of oxygen (FIO2) during the perioperative period has been reported
      to be of benefit in selected patients, but its role as a routine intervention has
      not been investigated. OBJECTIVE: To determine whether the routine use of high
      FIO2 during the perioperative period alters the incidence of SSI in a general
      surgical population. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized
      controlled trial conducted between September 2001 and May 2003 at a large
      university hospital in metropolitan New York City of 165 patients undergoing
      major intra-abdominal surgical procedures under general anesthesia.
      INTERVENTIONS: Patients were randomly assigned to receive either 80% oxygen (FIO2
      of 0.80) or 35% oxygen (FIO2 of 0.35) during surgery and for the first 2 hours
      after surgery. MAIN OUTCOME MEASURES: Presence of clinically significant SSI in
      the first 14 days after surgery, as determined by clinical assessment, a
      management change, and at least 3 prospectively defined objective criteria.
      RESULTS: The study groups were closely matched in a large number of clinical
      variables. The overall incidence of SSI was 18.1%. In an intention-to-treat
      analysis, the incidence of infection was significantly higher in the group
      receiving FIO2 of 0.80 than in the group with FIO2 of 0.35 (25.0% vs 11.3%; P
      =.02). FIO2 remained a significant predictor of SSI (P =.03) in multivariate
      regression analysis. Patients who developed SSI had a significantly longer length
      of hospitalization after surgery (mean [SD], 13.3 [9.9] vs 6.0 [4.2] days;
      P<.001). CONCLUSIONS: The routine use of high perioperative FIO2 in a general
      surgical population does not reduce the overall incidence of SSI and may have
      predominantly deleterious effects. General surgical patients should continue to
      receive oxygen with cardiorespiratory physiology as the principal determinant.

PMID- 14709580
TI  - Family perspectives on end-of-life care at the last place of care.
AB  - CONTEXT: Over the past century, nursing homes and hospitals increasingly have
      become the site of death, yet no national studies have examined the adequacy or
      quality of end-of-life care in institutional settings compared with deaths at
      home. OBJECTIVE: To evaluate the US dying experience at home and in institutional
      settings. DESIGN, SETTING, AND PARTICIPANTS: Mortality follow-back survey of
      family members or other knowledgeable informants representing 1578 decedents,
      with a 2-stage probability sample used to estimate end-of-life care outcomes for
      1.97 million deaths from chronic illness in the United States in 2000. Informants
      were asked via telephone about the patient's experience at the last place of care
      at which the patient spent more than 48 hours. MAIN OUTCOME MEASURES: Patient-
      and family-centered end-of-life care outcomes, including whether health care
      workers (1) provided the desired physical comfort and emotional support to the
      dying person, (2) supported shared decision making, (3) treated the dying person
      with respect, (4) attended to the emotional needs of the family, and (5) provided
      coordinated care. RESULTS: For 1059 of 1578 decedents (67.1%), the last place of
      care was an institution. Of 519 (32.9%) patients dying at home represented by
      this sample, 198 (38.2%) did not receive nursing services; 65 (12.5%) had home
      nursing services, and 256 (49.3%) had home hospice services. About one quarter of
      all patients with pain or dyspnea did not receive adequate treatment, and one
      quarter reported concerns with physician communication. More than one third of
      respondents cared for by a home health agency, nursing home, or hospital reported
      insufficient emotional support for the patient and/or 1 or more concerns with
      family emotional support, compared with about one fifth of those receiving home
      hospice services. Nursing home residents were less likely than those cared for in
      a hospital or by home hospice services to always have been treated with respect
      at the end of life (68.2% vs 79.6% and 96.2%, respectively). Family members of
      patients receiving hospice services were more satisfied with overall quality of
      care: 70.7% rated care as "excellent" compared with less than 50% of those dying
      in an institutional setting or with home health services (P<.001). CONCLUSIONS:
      Many people dying in institutions have unmet needs for symptom amelioration,
      physician communication, emotional support, and being treated with respect.
      Family members of decedents who received care at home with hospice services were
      more likely to report a favorable dying experience.

PMID- 14709581
TI  - Physician-citizens--public roles and professional obligations.
AB  - Although leaders and other commentators have called for the medical profession's
      greater engagement in improving systems of care and population health, neither
      medical education nor the practice environment has fostered such engagement.
      Missing have been a clear definition of physicians' public roles, reasonable
      limits to what can be expected, and familiarity with tasks that are compatible
      with busy medical practices. We address these issues by proposing a definition
      and a conceptual model of public roles that require evidence of disease causation
      and are guided by the feasibility and efficacy of physician involvement. We then
      frame a public agenda for individual physicians and physician organizations that
      focuses on advocacy and community participation. By doing so, we aim to stimulate
      dialogue about the appropriateness of such roles and promote physician engagement
      with pressing health issues in the public arena.

PMID- 14709582
TI  - Health effects of climate change.

PMID- 14709583
TI  - The complex world of prescribing behavior.

PMID- 14709586
TI  - STUDENTJAMA. Ethical issues in medical education.

PMID- 14709587
TI  - STUDENTJAMA. Teaching invasive procedures to medical students.

PMID- 14709588
TI  - STUDENTJAMA. Medical student care of indigent populations.

PMID- 14709589
TI  - STUDENTJAMA. Unclaimed bodies at the anatomy table.

PMID- 14709590
TI  - STUDENTJAMA. Living with the patient.

PMID- 14709591
TI  - JAMA patient page. Prenatal care.

PMID- 14709592
TI  - Interactive effects of MC1R and OCA2 on melanoma risk phenotypes.
AB  - The relationships between MC1R gene variants and red hair, skin reflectance,
      degree of freckling and nevus count were investigated in 2331 adolescent twins,
      their sibs and parents in 645 twin families. Penetrance of each MC1R variant
      allele was consistent with an allelic model where effects were multiplicative for
      red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed,
      four common alleles were strongly associated with red hair and fair skin
      (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles
      having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were
      separately combined for the purposes of this analysis and designated as strong
      'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair
      alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups
      with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye
      color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye
      color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln),
      which were confirmed as modifying eye color. MC1R genotype effects on
      constitutive skin color, freckling and mole count were modified by eye color, but
      not genotype for these two OCA2 SNPs. This is probably due to the association of
      these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a
      R/R genotype (but not R/r), those who also had brown eyes had a mole count twice
      that of those with blue eyes. This suggests that other OCA2 polymorphisms
      influence mole count and remain to be described.

PMID- 14709593
TI  - Behavioral characterization of mouse models for Smith-Magenis syndrome and
      dup(17)(p11.2p11.2).
AB  - Contiguous gene syndromes (CGS) refer to a group of disorders associated with
      chromosomal rearrangements in which the phenotype is thought to result from
      altered copy number of physically linked dosage-sensitive genes. Smith-Magenis
      syndrome and [dup(17)(p11.2p11.2)] are CGS associated with a heterozygous
      deletion or duplication of band p11.2 of chromosome 17, respectively. We
      previously constructed animal models for these CGSs by engineering rearranged
      chromosomes carrying a deletion/deficiency [Df(11)17] (Del mutant) or a
      duplication [Dp(11)17 ] (Dup mutant) of the syntenic region on mouse chromosome
      11. Here we present a behavioral analysis of these models indicating that
      heterozygous male mice carrying the engineered deletion or the duplication are
      hypoactive or hyperactive, respectively. In addition, male Dup mutant mice, but
      not Del mutant mice, have impaired contextual fear conditioning. Circadian rhythm
      studies revealed period length differences in Del mutant mice, but not Dup mutant
      mice. These results indicate that some of the behavioral abnormalities are gene
      dosage sensitive, whereas other behavioral abnormalities are specific to mice
      carrying the deletion or the duplication and can be observed in a sex
      preferential manner. Our findings suggest that there is a gene(s) present in this
      defined genomic interval that is responsible for behavioral abnormalities in the
      mouse, as has been shown for the human syntenic region.

PMID- 14709594
TI  - A screen for drugs that protect against the cytotoxicity of polyglutamine
      expanded androgen receptor.
AB  - Spinobulbar muscular atrophy is a neurodegenerative disorder caused by expansion
      of a CAG triplet repeat sequence encoding a polyglutamine tract in the androgen
      receptor. It has been shown that the mutant protein is toxic in cell culture and
      triggers an apoptotic cascade resulting in activation of caspase-3. We developed
      an assay of caspase-3 activation in cells expressing the mutant androgen
      receptor. This assay was used to screen 1040 drugs, most of which are approved
      for clinical use. Drugs that inhibit polyglutamine-dependent activation of
      caspase-3 were subjected to follow-up screens to identify compounds that
      reproducibly prevent polyglutamine-induced cytotoxicity. Four drugs satisfied
      these criteria. Three of these (digitoxin, nerifolin and peruvoside) are
      structurally and functionally related compounds of the cardiac glycoside class
      and known inhibitors of Na(+)K(+)-ATPase. The fourth compound, suloctidil, is a
      calcium channel blocker.

PMID- 14709595
TI  - Rescue of a human mRNA splicing defect by the plant cytokinin kinetin.
AB  - The defective splicing of pre-mRNA is a major cause of human disease. Exon
      skipping is a common result of splice mutations and has been reported in a wide
      variety of genetic disorders, yet the underlying mechanism is poorly understood.
      Often, such mutations are incompletely penetrant, and low levels of normal
      transcript and protein are maintained. Familial dysautonomia (FD) is caused by
      mutations in IKBKAP, and all cases described to date involve an intron 20
      mutation that results in a unique pattern of tissue-specific exon skipping.
      Accurate splicing of the mutant IKBKAP allele is particularly inefficient in the
      nervous system. Here we show that treatment with the plant cytokinin kinetin
      alters splicing of IKBKAP. Kinetin significantly increases inclusion of exon 20
      from the endogenous gene, as well as from an IKBKAP minigene. By contrast the
      drug does not enhance inclusion of alternatively spliced exon 31 in MYO5A.
      Benzyladenine, the most closely related cytokinin, showed a similar but less
      dramatic effect. Our findings reveal a remarkable impact on splicing fidelity by
      these small molecules, which therefore provide new tools for the dissection of
      mechanisms controlling tissue-specific pre-mRNA splicing. Further, kinetin should
      be explored as a treatment for increasing the level of normal IKAP in FD, and for
      other splicing disorders that may share a similar mechanism.

PMID- 14709596
TI  - Association between schizophrenia with ocular misalignment and polyalanine length
      variation in PMX2B.
AB  - The increased incidence of minor physical anomalies (MPAs) in schizophrenia is
      the fundamental basis for the neurodevelopmental hypothesis of schizophrenia
      etiology. Ocular misalignment, or strabismus, falls into the category of MPAs,
      but this phenotype has not been assessed in schizophrenia. This study reveals
      that a subtype of strabismus, constant exotropia, displays marked association
      with schizophrenia (P=0.00000000906). To assess the genetic mechanisms, we
      examined the transcription factor genes ARIX (recently identified as a causative
      gene for syndromic strabismus) and its paralogue, PMX2B. We identified frequent
      deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B,
      with a modest association between these functional polymorphisms and constant
      exotropia in schizophrenia (P=0.029). The polymorphisms were also associated with
      overall schizophrenia (P=0.012) and more specifically with schizophrenia
      manifesting strabismus (P=0.004). These results suggest a possible interaction
      between PMX2B and other schizophrenia-precipitating factors, increasing the risk
      of the combined phenotypes. This study also highlights the unique nature of the
      polyalanine length variations found in PMX2B. In contrast with other
      transcription factor genes, the variations in PMX2B show a high prevalence, with
      deletions being more common than insertions. Additionally, the polymorphisms are
      of ancient origin and stably transmitted, with mild phenotypic effects. In
      summary, our study lends further support to the disruption of neurodevelopment in
      the etiology of schizophrenia, by demonstrating the association of a specific
      MPA, in this case, constant exotropia with schizophrenia, along with molecular
      variations in a possible causative gene.

PMID- 14709597
TI  - Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the
      retinoid cycle: a reappraisal of the human disease sequence.
AB  - Mutations in ABCA4, which encodes a photoreceptor specific ATP-binding cassette
      transporter (ABCR), cause autosomal recessive forms of human blindness due to
      retinal degeneration (RD) including Stargardt disease. The exact disease sequence
      leading to photoreceptor and vision loss in ABCA4-RD is not known. Extrapolation
      from murine and in vitro studies predicts that two of the earliest
      pathophysiological features resulting from disturbed ABCR function in man would
      be slowed kinetics of the retinoid cycle and accelerated deposition of lipofuscin
      in the retinal pigment epithelium (RPE). To determine the human pathogenetic
      sequence, we studied surrogate measures of retinoid cycle kinetics, lipofuscin
      accumulation, and rod and cone photoreceptor and RPE loss in ABCA4-RD patients
      with a wide spectrum of disease severities. There were different extents of
      photoreceptor/RPE loss and lipofuscin accumulation in different regions of the
      retina. Slowing of retinoid cycle kinetics was not present in all patients; when
      present, it was not homogeneous across the retina; and the extent of slowing
      correlated well with the degree of degeneration. The orderly relationship between
      these phenotypic features permitted the development of a model of disease
      sequence in ABCA4-RD. The model predicted lipofuscin accumulation as a key and
      early component of the disease expression in man, as in mice. In man, however,
      abnormal slowing of the rod and cone retinoid cycle occurs at later stages of the
      disease sequence. Knowledge of the human ABCA4 disease sequence will be critical
      for defining rates of progression, selecting appropriate patients and retinal
      locations for future therapy, and choosing appropriate treatment outcomes.

PMID- 14709598
TI  - Acrodermatitis enteropathica mutations affect transport activity, localization
      and zinc-responsive trafficking of the mouse ZIP4 zinc transporter.
AB  - The Zip4 protein is involved in dietary zinc uptake from the intestinal lumen.
      The human ZIP4 gene (SLC39A4) was identified because of its association with
      acrodermatitis enteropathica (AE), a genetic disorder of zinc absorption. To
      date, several SLC39A4 mutations have been identified in AE patients. To
      investigate the effects of these mutations on function of the Zip4 transporter,
      we introduced six AE-associated missense mutations into the orthologous mouse
      ZIP4 gene for functional expression in cultured cells. All mutations decreased
      65Zn uptake activity of mZip4, thereby providing a causal link to AE. The mutants
      fell into two groups based on their phenotypic effects. Several alleles (G340D,
      L382P, G384R, G643R) failed to localize on the cell surface at high levels. These
      defects were attributable to misfolding and/or mislocalization in the secretory
      pathway. Two other alleles (P200L and G539R) accumulated to high levels in the
      plasma membrane and had wild-type apparent Km values for 65Zn uptake. However,
      these mutations decreased the Vmax of uptake to approximately 30% of wild-type.
      We showed previously that wild-type mZip4 is regulated post-translationally in
      response to zinc status. In zinc-replete cells, mZip4 is found largely in
      intracellular compartments. In zinc-limited cells, surface levels increase
      markedly because the rate of endocytosis decreases. Surprisingly, endocytosis of
      both P200L and G539R is no longer zinc responsive; these proteins are endocytosed
      at a slow rate regardless of zinc status. These effects suggest a zinc sensing
      mechanism for regulating Zip4 trafficking in response to zinc.

PMID- 14709599
TI  - Deficiency of the first mannosylation step in the N-glycosylation pathway causes
      congenital disorder of glycosylation type Ik.
AB  - Defects of N-linked glycosylation represent diseases with multiple organ
      involvements that are classified as congenital disorders of glycosylation (CDG).
      In recent years, several CDG types have been attributed to defects of dolichol
      linked oligosaccharide assembly in the endoplasmic reticulum. The profiling of
      [3H]mannose-labeled lipid-linked oligosaccharides was instrumental in identifying
      most of these glycosylation disorders. However, this method is poorly suited for
      the identification of short lipid-linked oligosaccharide biosynthesis defects. To
      adequately resolve deficiencies affecting the first steps of lipid-linked
      oligosaccharide formation, we have used a non-radioactive procedure employing the
      fluorescence detection of 2-aminobenzamide-coupled oligosaccharides after HPLC
      separation. By applying this method, we have detected the accumulation of
      dolichylpyrophosphate-GlcNAc2 in a previously untyped CDG patient. The
      accumulation pattern suggested a deficiency of the ALG1 beta1,4
      mannosyltransferase, which adds the first mannose residue to lipid-linked
      oligosaccharides. This was supported by the finding that this CDG patient was
      compound heterozygous for three mutations in the ALG1 gene, leading to the amino
      acid substitutions S150R and D429E on one allele and S258L on the other. The
      detrimental effect of these mutations on ALG1 protein function was demonstrated
      in a complementation assay using alg1 Saccharomyces cerevisiae yeast mutants. The
      ALG1 mannosyltransferase defect described here represents a novel type of CDG,
      which should be referred to as CDG-Ik.

PMID- 14709600
TI  - Human tra2-beta1 autoregulates its protein concentration by influencing
      alternative splicing of its pre-mRNA.
AB  - HTRA2-BETA1 is an SR-like protein that regulates alternative splice site
      selection in a concentration-dependent manner. Its proper concentration is
      important as several pathological states are associated with its change. We
      investigated the mechanism that controls the cellular HTRA2-BETA1 concentration
      and found it utilizes a negative feedback loop to regulate the splicing of its
      exon 2. TRA2-BETA1 binds to four enhancers present in exon 2, which activates its
      inclusion. Inclusion of exon 2 generates mRNAs that are not translated into
      proteins. Mutations of exon 2 enhancers demonstrate that TRA2-BETA1 binds a
      degenerate sequence GHVVGANR, which is found more frequently in exons than in
      introns. Hyperphosphorylation of TRA2-BETA1 strongly reduces its binding to RNA.
      Presence of the CLK2 kinase prevents the usage of exons 2 and 3, generating the
      htra2-beta3 mRNA. The resulting HTRA2-BETA3 protein lacks the first RS domain of
      HTRA2-BETA1, is expressed in several tissues and has no influence on tra2-beta
      splice site selection. HTRA2-BETA1 interacting proteins promote exon 2 skipping
      by sequestering it, which upregulates the HTRA2-BETA1 protein synthesis. We
      propose that the regulation of the tra2-beta pre-mRNA alternative splicing
      provides a robust and sensitive molecular sensor that measures the ratio between
      HTRA2-BETA1 and its interacting proteins.

PMID- 14709601
TI  - Intraosseous oral leiomyoma: systematic review and report of one case.
AB  - OBJECTIVES: The objectives of this study were to report one case of intraosseous
      oral leiomyoma and to systematically review the English literature. METHODS: The
      clinical and radiographic findings of a patient who presented with intraosseous
      oral leiomyoma were recorded. In addition, 11 references from the English
      literature that reported 12 patients were reviewed. RESULTS: Thirteen patients
      (age range 8 months to 71 years; mean 36 years, median 25 years) were reported to
      present with intraosseous oral leiomyoma. After excluding one patient whose sex
      was not reported, there were five female patients (42%) and seven males (58%).
      The majority of patients presented with either no symptoms or with an
      asymptomatic swelling. Eleven of 13 lesions occurred in the mandible; the most
      common site was the posterior of the jaw. Radiographically, intraosseous oral
      leiomyoma was found to present as either a unilocular or multilocular
      radiolucency with either well defined or ill defined borders and frequent
      cortical involvement. CONCLUSIONS: Intraosseous oral leiomyoma was found to occur
      in the mandibular posterior region of relatively young patients, with cortical
      involvement and a slight male gender preference. Surgical excision was the
      treatment of choice and no recurrence has been encountered.

PMID- 14709602
TI  - Maxillary bone invasion by gingival carcinoma as an indicator of cervical
      metastasis.
AB  - OBJECTIVES: To evaluate the significance of maxillary bone invasion by gingival
      carcinoma as an indicator of cervical metastasis. METHODS: Twenty-one patients
      with squamous cell carcinoma of the upper gingiva were included in the study. The
      extent of bone invasion was assessed by dental CT. Six patients had cervical
      metastases at the initial examination and eight more developed them during the 2
      year follow-up period. The relationship of cervical metastases with age and
      gender of these patients, as well as with the size of the lesion and extent of
      bone invasion, was examined by logistic multivariate regression analysis.
      RESULTS: There was a significant relationship between the presence of bone
      invasion and the presence of cervical metastasis (P<0.05). CONCLUSIONS: Maxillary
      bone invasion is an indicator of cervical metastasis in gingival carcinoma.

PMID- 14709603
TI  - Usefulness of heavily T(2) weighted magnetic resonance images for the
      differential diagnosis of parotid tumours.
AB  - OBJECTIVES: To evaluate the usefulness of heavily T(2) weighted (T2W) magnetic
      resonance (MR) images for the differential diagnosis of parotid tumours. METHODS:
      Conventional T2W and heavily T2W images obtained from 43 patients with parotid
      tumours were reviewed retrospectively. Tumours were classified pathologically
      into three types: pleomorphic adenoma (25 cases), Warthin's tumour (7 cases) and
      malignant tumour (11 cases). During interpretation of each MR image, special
      attention was paid to the homogeneity and signal intensity displayed by the solid
      portions of the tumours. RESULTS: Heavily T2W images could distinguish
      pleomorphic adenoma from Warthin's tumour and malignant tumours based on the
      homogeneity and signal intensity of the solid portions, whereas conventional T2W
      images could not. On conventional T2W images, neither homogeneity nor signal
      intensity differed significantly among these three tumour types. On heavily T2W
      images, malignant and Warthin's tumours appeared more homogeneous than
      pleomorphic adenoma (P<0.0061); signal intensity from pleomorphic adenoma was
      significantly different to signal intensity from malignant tumours (P<0.05) and
      Warthin's tumour (P<0.005). CONCLUSIONS: Heavily T2W MR images can be useful in
      distinguishing pleomorphic adenoma from Warthin's tumour and malignant tumours.

PMID- 14709604
TI  - Evaluation of coronal CT findings of rare cases of isolated medial orbital wall
      blow-out fractures.
AB  - OBJECTIVES: To report rare cases of isolated medial orbital wall blow-out
      fractures and to evaluate their coronal CT findings. METHODS: Nine cases of
      medial orbital wall blow-out fractures, diagnosed by coronal CT in a general
      medical hospital between 1995 and 1999, were studied. CT was performed using
      direct coronal acquisition with a slice thickness of 5 mm. Images were obtained
      at bone window settings. Clinical examination findings from the medical records
      were used to give information on the cause of injury, ocular symptoms and the
      days after injury that the CT examination was performed. RESULTS: Most of the
      patients (67%) were young male adults. The cause of injury was most frequently
      the result of fist fighting or athletics (78%). Diplopia and/or limitation of the
      gaze were the main ocular symptoms (78%). The average time from injury to CT
      examination was 4 days (range 0-16 days). Seven of the nine patients with medial
      orbital wall fractures had isolated medial orbital wall blow-out fractures.
      Herniation of orbital contents toward the ethmoid sinus was observed among all
      nine fractures. Only three patients (33%) had a swelling and/or medial deviation
      of the medial rectus muscle, all three having isolated medial orbital wall blow
      out fractures. CONCLUSIONS: Nine cases of medial orbital wall blow-out fractures
      were examined, seven of which were isolated medial wall blow-out fractures. CT
      findings of this type of fracture included herniation of the orbital contents
      toward the ethmoid sinus. However, swelling and/or medial deviation of the medial
      rectus muscle was also seen.

PMID- 14709605
TI  - Temporomandibular internal derangement: correlation of MRI findings with clinical
      symptoms of pain and joint sounds in patients with bruxing behaviour.
AB  - OBJECTIVES: The aim of this study was to correlate magnetic resonance imaging
      (MRI) findings of effusion, disc displacement, condylar bony changes and disc
      form with clinical findings of pain and sounds in patients with bruxing and non
      bruxing behaviour. METHODS: Disc displacement was confirmed by MRI in 102 joints
      from 64 patients (total of 128 joints) with bruxing behaviour who were referred
      for clinically diagnosed internal derangements of the temporomandibular joint
      (TMJ). Sixty joints with internal derangement from 30 patients without bruxing
      behaviour served as a control group. The clinical inclusion criteria were pain in
      the pre-auricular area and muscles of mastication, limitation or deviation in
      mandibular range of motion, and TMJ sounds. Signs of bruxism were diagnosed
      clinically and were obtained from the patient's history given on their first
      visit. Pain was evaluated using a visual analogue scale. RESULTS: Of the 102
      joints in the study group with disc displacement, 53 (52%) showed disc
      displacement with reduction and 49 (48%) showed disc displacement without
      reduction. In the control group, 16 joints were classified as normal. Of the
      remaining 44 joints, 27 (61%) had disc displacement with reduction and 17 (39%)
      had unilateral disc displacement without reduction. Condylar bony changes were
      seen in 55% of the reducing joints in the study group and in 38% of the reducing
      joints in the control group, compared with 86% of the non-reducing joints in the
      study group and 24% of the non-reducing joints in the control group. There was a
      strong correlation between age and degenerative change in the study group. In the
      reducing joints, there was a significant difference in the prevalence of condylar
      bony changes between the study and control groups (P<0.01). In non-reducing
      joints, 30% of painful joints in the study group and 59% of those in the control
      group showed a strong signal in the joint space on T(2) weighted imaging.
      Statistically significant differences between the study and control groups were
      also found for disc form and the prevalence of effusion and disc displacement.
      Joint sounds were important in unilaterally affected joints in the study group. A
      statistically significant correlation was found between joint sounds and reducing
      joints (P<0.05). CONCLUSION: It was demonstrated that a higher prevalence of
      condylar bony changes occurred in reducing joints in patients with bruxing
      behaviour.

PMID- 14709606
TI  - Snoring, sleep apnoea and swallowing dysfunction: a videoradiographic study.
AB  - OBJECTIVES: Snoring is associated with subclinical pharyngeal swallowing
      dysfunction, probably owing to vibration trauma to the pharyngeal tissues caused
      by snoring. Negative intrathoracic pressure during apnoea causes stretching of
      the velum and pharynx. The aim of this study was to investigate whether patients
      with severe sleep apnoea have an increased frequency of videoradiographically
      diagnosed subclinical pharyngeal swallowing dysfunction compared with snoring
      patients with or without mild sleep apnoea as well as with non-snoring controls.
      METHODS: Eighty consecutive patients referred for sleep apnoea recordings because
      of snoring were examined. Fourteen of these patients were excluded because they
      suffered from dysphagia. Fifteen non-snoring, non-dysphagic volunteers served as
      controls. Videoradiography was performed to examine the oral and pharyngeal
      swallowing function in patients and controls. Overnight sleep apnoea recordings
      were used to evaluate the apnoea-hypopnoea index (AHI). RESULTS: Pharyngeal
      swallowing dysfunction was observed in 34/66 (52%) of the snoring patients and in
      1/15 (7%) of the non-snoring controls. Pharyngeal swallowing dysfunction was
      observed in 50% of patients with an AHI of >or=30, in 61% of patients with an AHI
      of 5-29 and in 43% of patients with an AHI of <5. There was no significant
      difference in the frequency of pharyngeal swallowing dysfunction between snoring
      patients with different AHIs. CONCLUSION: Snoring patients run an increased risk
      of developing subclinical pharyngeal swallowing dysfunction independent of
      concomitant sleep apnoea.

PMID- 14709607
TI  - Bitewing examination with four digital receptors.
AB  - OBJECTIVES: To evaluate recording errors and patient discomfort during bitewing
      examinations using four digital receptors. METHODS: Seventy-eight patients had
      two bitewings taken on each side of the mouth with the intention of displaying
      the tooth surfaces from the distal surface of the canine to the distal surface of
      the most posterior molar, using four digital receptors, two charge-coupled device
      (CCD) and two photostimulable phosphor (PSP) systems. The patients scored their
      feelings of discomfort during the examination on a visual analogue scale.
      Receptor positioning errors in the sagittal plane were determined from the tooth
      surfaces present on each image and in the vertical plane from the presence of the
      alveolar bone crest. Cone positioning errors were determined from cone cuts.
      RESULTS: Canine and premolar surfaces were more often not depicted on the CCD
      images than on the PSP images (P<0.05). Cone cuts occurred in 19% of DenOptix
      images, in 9% of Digora images and in one Planmeca image. The bone crest was more
      often missing in the upper jaw on Planmeca images than on PSP images (P<0.01). In
      the lower jaw, Trophy images more often missed the bone crest than the other
      systems (P<0.05). Patients ranked the receptors as follows (with increasing
      discomfort): DenOptix, Planmeca, Digora and Trophy, with all being significantly
      different (P<0.05). CONCLUSIONS: It was more difficult to correctly position CCD
      sensors than PSP plates in the vertical plane, resulting in more images with
      missing alveolar bone crest. CCD sensors most often did not display the most
      anterior surfaces in a bitewing examination.

PMID- 14709608
TI  - Quality of digital pre-implant tomography: comparison of film-screen images with
      storage phosphor images at normal and low dose.
AB  - OBJECTIVES: The aim of this pilot study was to compare the image quality of a
      storage phosphor system with that of conventional film-screen in pre-implant
      conventional tomography, and to test the influence of radiation dose on image
      quality in the storage phosphor system. METHODS: Cross-sectional conventional
      tomographic images (Scanora) technique) were obtained on 11 patients with film
      screen and with storage phosphor image plates (Digora) PCT) at normal and low
      doses. Ten observers graded the visibility of anatomical structures of importance
      for implant planning. A three-step rating scale was used, where -1 =worse,
      0=equal and 1=better than the reference image. RESULTS: Although image quality
      was graded as equally good in the majority (59%) of images, the storage phosphor
      system scored significantly lower than film-screen (-0.37 vs 0.00, respectively)
      for all the images. Low dose storage phosphor images were rated significantly
      lower (-0.21) than normal dose images (0.00). CONCLUSIONS: In the majority of
      patients, anatomic structures of importance for implant planning are visualized
      equally well on storage phosphor and film-screen images. However, where
      differences do exist, storage phosphor images score lower than film-screen
      images. Dose reduction in the storage phosphor system had a negative influence on
      image quality.

PMID- 14709609
TI  - Radiation absorbed doses at compact bone-titanium interfaces in diagnostic
      radiography: a Monte Carlo approach.
AB  - OBJECTIVES: The aim of this study was to estimate the radiation absorbed dose at
      cortical tissue-implant interfaces in diagnostic radiology. METHODS: Since our
      interest was the radiation dose at an interface (cortical bone-implant
      interface), a Monte Carlo simulation was considered to be the most suitable
      method for studying the problem. The Monte Carlo code employed was MCNP4B. A
      phantom consisting of soft tissue, cortical bone, an implant and air, with
      appropriate chemical compositions and densities, was described in the code. The
      implant simulated had a commercial name of ASTM67, grade 2 and was 1.9 mm wide.
      The incident photon beam was divergent of 20 cm x 20 cm at a source-to-phantom
      distance of 40 cm. Two energy spectra were employed (70 kVp and 100 kVp, 0.5 mm
      Al internal filtration) and their photon fluence distribution against energy was
      described in the code with an energy interval of 5 keV. The computations that led
      to radiation dose calculations had a spatial resolution of 0.01 cm (100 microm)
      to allow a detailed radiation dose distribution across the cortical bone-titanium
      interface. Monte Carlo runs took place both with and without an implant in the
      phantom and, in each case, 120 million photon histories were followed, leading to
      a radiation dose statistical fluctuation between 5% and 10%. RESULTS: The ratio
      of radiation dose with implant to dose without implant against depth allows a
      direct estimate of the effect of the implant on the radiation dose to the
      cortical bone surrounding the implant. At a distance >or=100 microm there was no
      radiation dose increase due to the titanium implant. However, in contact with the
      implant (i.e. the first layers of cells) there was a sharp radiation dose
      increase as high as 3.5 times the radiation dose compared with when the implant
      was absent. Also, the newly formed bone inside the implant's tiny hole received a
      radiation dose close to 50% of the radiation dose without the implant owing to
      high absorption by the implant itself. CONCLUSIONS: Assuming that the patient
      received five radiographic images over a 6-month period, the maximum radiation
      dose at the cortical bone-titanium interface was estimated to be less than 20 mGy
      (0.02 Gy).

PMID- 14709610
TI  - MRI findings in lingual venous malformations.
AB  - OBJECTIVES: To describe the plain and enhanced MRI findings of lingual venous
      malformations and to discuss the importance of contrast medium in the
      differential diagnosis of high intensity lesions of the tongue on T(2) weighted
      images. METHODS: The clinical records and MR images of eight patients affected by
      a lingual venous malformation were retrospectively reviewed. Patients presented
      with a palpable submucosal bluish-red soft mass in the tongue. MRI examinations
      were performed on a 0.5 T superconducting unit. Plain and enhanced SE (spin echo)
      T(1) weighted and FSE (fast spin echo) T(2) weighted images were acquired in
      axial, sagittal and coronal planes. Axial SPGR (spoiled gradient recalled echo)
      T(1) weighted images were also obtained before and after intravenous (i.v.)
      injection of paramagnetic contrast medium. RESULTS: Five of eight venous
      malformations were located at the tip of the tongue. The other three involved the
      whole tongue and had an extralingual extent; two extended into the submandibular
      space and one into the glossoepiglottic valleculae. The largest diameter ranged
      from 2.5 cm to 8 cm. All lingual venous malformations presented as lobulated
      masses that were slightly hyperintense or isointense on T(1) weighted images and
      highly hyperintense on T(2) weighted images with respect to normal tongue and/or
      surrounding muscles. They showed a slow and homogeneous filling following iv
      injection of contrast medium. Millimetre-sized hypointense foci and linear
      hypointense strands were sometimes noticed, which were owing to phleboliths, flow
      void or septation. CONCLUSION: Knowledge of MRI findings of lingual venous
      malformations is useful for differential diagnosis with other high intensity
      lingual lesions on T(2) weighted images. This discrimination is achievable using
      iv paramagnetic contrast medium.

PMID- 14709611
TI  - Integration of multiple direct digital imaging sources in a picture archiving and
      communication system (PACS).
AB  - OBJECTIVES: The aim of this report was to describe a flexible picture archiving
      and communication system (PACS) able to handle and communicate digital image data
      from various radiography systems and other sources. METHODS: The radiographic
      image is acquired using the vendor's own software. Following image capture, a
      "request for update" message (appending a record to an Access database) activates
      our PACS engine, "DigiMerge". Images from sources with no patient-related
      organizing software, e.g. TWAIN-compatible scanners and digital cameras, are
      handled by a self-developed program, "MedCom-T". DigiMerge generates and
      maintains one database based on all manufacturers' databases (software: VixWin
      2000, Digora for Windows, Dimaxis Pro, Sidexis, CDR DICOM for Windows, Trophy for
      Windows). This database contains patient information, image information and image
      path. The program "DigiView" searches a patient and displays patient and image
      data from the database generated by DigiMerge. With DigiView, images can be
      viewed at any workstation in the dental school, but only temporary changes can be
      made (contrast, brightness, etc.) and no image can be deleted. RESULTS: The PACS
      is currently installed on 86 workstations. Statistics collected by DigiMerge
      reveal that approximately 2000 new digital images are recorded each month, half
      of which are radiographs and the other half are clinical photographs. Statistics
      collected by DigiView reveal that 500-800 digital images are opened per week.
      CONCLUSIONS: The self-developed PACS is able to manage images from a range of
      digital modalities each providing its own image data format.

PMID- 14709612
TI  - Primary Ewing's sarcoma of the paranasal sinus with intracranial extension:
      imaging features.
AB  - Extraskeletal Ewing's sarcoma is often described as a tumour involving the soft
      tissues of the lower extremities and the paravertebral region. Involvement of the
      paranasal sinus is a very rare entity. We present a case of primary Ewing's
      sarcoma of the paranasal sinus extending into the middle cranial fossa in a 40
      year-old female. CT and MRI findings of this unusual case are discussed. To our
      knowledge, this case is the first to be reported with CT and MRI documentation.

PMID- 14709613
TI  - Jud Coon: 35 years of p450 research, a synopsis of p450 history.
AB  - The year 2004 marks the 50th anniversary of the discovery of cytochrome P450.
      Minor J. (Jud) Coon has been a leader in this field for the last 35 years. This
      review summarizes his contributions to P450 research by discussing six of his
      most significant publications; not surprisingly, these papers serve as landmarks
      for the major directions followed in P450 research.

PMID- 14709614
TI  - Catalytic roles of CYP2C9 and its variants (CYP2C9*2 and CYP2C9*3) in lornoxicam
      5'-hydroxylation.
AB  - The effects of allelic variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) on lornoxicam
      5'-hydroxylation were studied using the corresponding variant protein expressed
      in baculovirus-infected insect cells and human liver microsomes of known
      genotypes of CYP2C9. The results of the baculovirus expression system showed that
      CYP2C9.3 gives higher K(m) and lower V(max) values for lornoxicam 5'
      hydroxylation than does CYP2C9.1. In contrast, K(m) and V(max) values of CYP2C9.1
      and CYP2C9.2 for the reaction were comparable. Lornoxicam 5'-hydroxylation was
      also determined in liver microsomes of 12 humans genotyped for the CYP2C9 gene
      (*1/*1, n = 7; *1/*2, n = 2; *1/*3, n = 2; *3/*3, n = 1). A sample genotyped as
      *3/*3 exhibited 8- to 50-fold lower intrinsic clearance for lornoxicam 5'
      hydroxylation than did samples genotyped as *1/*1. However, the values for
      intrinsic clearance for *1/*3 were within the range of values exhibited by
      samples of *1/*1. In addition, no appreciable differences were observed in
      kinetic parameters for lornoxicam 5'-hydroxylation between *1/*1 and *1/*2. In
      conclusion, this study showed that lornoxicam 5'-hydroxylation via CYP2C9 was
      markedly decreased by the substitution of Ile359Leu (CYP2C9.3), whereas the
      effect of the substitution of Arg144Cys (CYP2C9.2) was nonexistent or negligible.
      Additional in vivo studies are required to confirm that individuals with
      homologous CYP2C9*3 allele exhibit impaired lornoxicam clearance.

PMID- 14709615
TI  - New secondary metabolites of phenylbutyrate in humans and rats.
AB  - Phenylbutyrate is used to treat inborn errors of ureagenesis, malignancies,
      cystic fibrosis, and thalassemia. High-dose phenylbutyrate therapy results in
      toxicity, the mechanism of which is unexplained. The known metabolites of
      phenylbutyrate are phenylacetate, phenylacetylglutamine, and
      phenylbutyrylglutamine. These are excreted in urine, accounting for a variable
      fraction of the dose. We identified new metabolites of phenylbutyrate in urine of
      normal humans and in perfused rat livers. These metabolites result from
      interference between the metabolism of phenylbutyrate and that of carbohydrates
      and lipids. The new metabolites fall into two categories, glucuronides and
      phenylbutyrate beta-oxidation side products. Two questions are raised by these
      data. First, is the nitrogen-excreting potential of phenylbutyrate diminished by
      ingestion of carbohydrates or lipids? Second, does competition between the
      metabolism of phenylbutyrate, carbohydrates, and lipids alter the profile of
      phenylbutyrate metabolites? Finally, we synthesized glycerol esters of
      phenylbutyrate. These are partially bioavailable in rats and could be used to
      administer large doses of phenylbutyrate in a sodium-free, noncaustic form.

PMID- 14709616
TI  - Suppression of drug-metabolizing enzymes and efflux transporters in the intestine
      of endotoxin-treated rats.
AB  - Infection and inflammation impose a suppression in the expression and activity of
      several drug transporters and drug-metabolizing enzymes in liver. In the
      intestine, cytochrome P450 3A (CYP3A), P-glycoprotein (PGP/mdr1), and the
      multidrug resistance-associated protein 2 (MRP2) are important barriers to the
      absorption of many clinically important drugs; thus, the expression and activity
      of these proteins were examined in inflammation. Transport and metabolism were
      determined in jejunum segments isolated at 24 h from endotoxin-treated or control
      rats (n = 8) mounted in Ussing chambers. Transport and metabolism of (3)H
      digoxin, 5-carboxyfluorescein (5-CF), amiodarone (AM), and 7-benzyloxyquinoline
      (7-BQ) were measured for 90 min in the presence and absence of inhibitors.
      Reverse transcription-polymerase chain reaction was used to measure mRNA levels.
      As compared with controls, levels of mdr1a and mrp2 mRNA were significantly
      decreased by approximately 50% in the jejunum of LPS-treated rats. Corresponding
      reductions in the basolateral-->apical efflux of digoxin, AM, and 5-CF were
      observed, resulting in significant increases in the apical-->basolateral
      absorption of these compounds. Intestinal CYP3A mRNA levels and CYP3A-mediated
      metabolism of 7-BQ and AM were also decreased by approximately 50 to 70% (p <
      0.05) in the LPS group. Mannitol permeability and lactate dehydrogenase release
      were not altered. These studies indicate that endotoxin-induced inflammation
      imposes a reduction in the intestinal expression and activity of PGP, mrp2, and
      CYP3A in rats, which elicits corresponding changes in the intestinal transport
      and metabolism of their substrates. Hence, infection and inflammatory diseases
      may impose variability in drug bioavailability through alterations in the
      intestinal expression and activity of drug transporters and metabolic enzymes.

PMID- 14709617
TI  - In vitro metabolism of hyperforin in rat liver microsomal systems.
AB  - Hyperforin is an important active component of St. John's wort (Hypericum
      perforatum) that has been suggested to be responsible for the St. John's wort
      antidepressive effects and herbal-drug interactions. In this study, the in vitro
      metabolism profile of hyperforin was investigated using liver microsomes from
      male and female Sprague-Dawley rats, with or without induction by phenobarbital
      or dexamethasone. Four major Phase I metabolites, named 19-hydroxyhyperforin, 24
      hydroxyhyperforin, 29-hydroxyhyperforin, and 34-hydroxyhyperforin, were isolated
      by high performance liquid chromatography and identified by mass spectrometry and
      NMR. Results suggest that hydroxylation is a major biotransformation of the
      hyperforin pathway in rat liver and that inducible cytochrome P450 3A (CYP450 3A)
      and/or CYP2B may be the major cytochrome P450 isoforms catalyzing these
      hydroxylation reactions.

PMID- 14709618
TI  - The pregnane X receptor binds to response elements in a genomic context-dependent
      manner, and PXR activator rifampicin selectively alters the binding among target
      genes.
AB  - The pregnane X receptor (PXR) is a key regulator of genes encoding several major
      types of cytochrome P450 enzymes and transporters (e.g., multidrug resistance-1,
      MDR1); therefore, PXR contributes significantly to drug-drug interactions. PXR
      binds to response elements and confers transactivation. Several target genes such
      as CYP3A4 and 3A7 contain two PXR elements (distant and proximal) that are
      separated by more than 7000 nucleotides in the genome. Disruption of the distant
      element causes a 73% decrease of the reporter activity, whereas inactivation of
      the proximal element decreases by only 53%. This study was undertaken to test the
      hypothesis that PXR differentially binds to the elements with the distant
      enhancer being bound to a higher extent. To test this hypothesis, a stable
      transfected line (hPXR-HRE) was prepared to constitutively express human PXR and
      harbor a chromatinized CYP3A4-ER6 reporter. This line responded to rifampicin and
      dexamethasone similarly as hepatocytes based on the relative potency and
      activation kinetics. Contrary to the hypothesis, chromatin immunoprecipitation
      experiments showed that the genomic fragment harboring the proximal element was
      preferably precipitated over the fragment containing the distant element in the
      CYP3A4 gene, but the opposite was true with the CYP3A7 gene. In addition, the
      promoters from the MDR1 and CYP2B6 genes were abundantly present in the PXR
      immunocomplexes from the vehicle-treated cells. However, such abundant
      interactions were markedly diminished when cells were treated with PXR activator
      rifampicin. These findings suggest that PXR binding is dependent on the genomic
      context and PXR activators modulate such bindings.

PMID- 14709619
TI  - N-acetylation of the glutamate residue of intact glutathione conjugates in rats:
      a novel pathway for the metabolic processing of thiol adducts of xenobiotics.
AB  - We report herein the identification of a novel metabolic pathway that involves
      acetylation of the amino group of the glutamic acid residue of intact glutathione
      (GSH) conjugates of a series of compounds in rat hepatocytes and in rats in vivo.
      The "nonacetylated" as well as the "acetylated" GSH conjugates of the compounds
      in question were detected in rat hepatocyte incubations and in rat bile. These
      conjugates were characterized by online liquid chromatography-mass spectrometry
      on an ion-trap mass spectrometer as well as accurate mass measurements using a
      high-resolution quadrupole time-of-flight instrument. The accurate mass
      measurements on the molecular ions of nonacetylated and acetylated GSH adducts
      clearly revealed the addition of a mass equivalent to C(2)H(2)O in the latter
      conjugates. Furthermore, the collision-induced dissociation of the molecular ions
      of nonacetylated GSH adducts yielded fragment ions involving the loss of
      pyroglutamate (129 Da), which are typical of many GSH conjugates. For acetylated
      adducts, however, fragment ions resulting from a loss of 171 Da (equivalent to N
      acetyl-pyroglutamate) were observed, indicating that acetylation had occurred on
      the glutamic acid residue of the GSH conjugates. An enzyme-catalyzed
      transacetylation process that utilized acetyl CoA as the acetyl donor, and
      resulted in the formation of the same acetylated adducts that were detected in
      rat hepatocytes and in rat bile, was identified in rat liver microsomes. This
      appears to be the first reported instance of N-acetylation of intact GSH
      conjugates in any species and represents a novel pathway of metabolic processing
      of thiol adducts of xenobiotics.

PMID- 14709620
TI  - Characterization of novel dihydrothienopyridinium and thienopyridinium
      metabolites of ticlopidine in vitro: role of peroxidases, cytochromes p450, and
      monoamine oxidases.
AB  - Ticlopidine is an agent that inhibits adenosine diphosphate-induced platelet
      aggregation. Metabolic studies with ticlopidine have indicated that the principal
      routes of metabolism are N-dealkylation, N-oxidation, and oxidation of the
      thiophene ring. However, ticlopidine shares some structural features that are
      similar to those of cyclic tertiary amines such as 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine and tetrahydroisoquinolines, which are converted to neurotoxic
      pyridinium metabolites, via the iminium (dihydropyridinium) species. The current
      in vitro studies examined the potential of ticlopidine to undergo a similar
      conversion by cytochrome P450 (P450), peroxidases, and monoamine oxidase (MAO).
      The results from these studies have suggested that ticlopidine undergoes an
      overall 4-electron oxidation to the novel thienopyridinium metabolite (M6) via
      the intermediate 2-electron oxidation product, the thienodihydropyridinium
      metabolite (M5) by P450, horseradish peroxidase, and myeloperoxidase and, to a
      lesser extent, by MAO. The structures of these metabolites were characterized by
      liquid chromatography (LC)-tandem mass spectrometry and LC-NMR. Qualitative
      studies with baculovirus-expressed P450s revealed the involvement of P450 3A4 in
      this conversion. Interestingly, M5 was the primary metabolite in the peroxidase
      mediated reactions and was quite stable to air oxidation or disproportionation.
      It was less electrophilic and did not form cyanide, glutathione, or N
      acetylcysteine adducts. On the other hand, M6 was the major metabolite in P450
      catalyzed oxidation of ticlopidine. The results from this study have revealed
      that in addition to metabolism of the thiophene ring of ticlopidine, the
      tetrahydropyridine moiety of the compound is susceptible to a 2-electron and a 4
      electron oxidation like other cyclic tertiary amines.

PMID- 14709621
TI  - Metabolism of apigenin by rat liver phase I and phase ii enzymes and by isolated
      perfused rat liver.
AB  - The metabolism of apigenin, a low estrogenic flavonoid phytochemical, was
      investigated in rat using liver models both in vitro (subcellular fractions) and
      ex vivo (isolated perfused liver). In vitro, phase I metabolism led to the
      formation of three monohydroxylated derivatives: luteolin which was the major
      metabolite (K(m) = 22.5 +/- 1.5 microM; V(max) = 5.605 +/- 0.090 nmol/min/mg
      protein, means +/- S.E.M.), scutellarein, and iso-scutellarein. These oxidative
      pathways were mediated by cytochrome P450 monooxygenases (P450s). The use of P450
      inhibitors and inducers showed that CYP1A1, CYP2B, and CYP2E1 are involved. In
      vitro studies of phase II metabolism indicated that apigenin underwent
      conjugation giving three monoglucuronoconjugates and one monosulfoconjugate.
      Luteolin led to the formation of four monoglucuronoconjugates, two
      sulfoconjugates, and one methylconjugate identified as diosmetin. Ex vivo during
      the apigenin perfusion of an isolated rat liver, none of the phase I metabolites
      could be recovered. In contrast, two monoglucuronoconjugates and one of the
      sulfoconjugates of apigenin already identified in vitro were recovered. Moreover,
      two new derivatives were isolated and identified as a diglucuronoconjugate and a
      glucuronosulfoconjugate. This work provides new data about the metabolism of
      apigenin and shows the interest value of using various experimental models in
      metabolic studies.

PMID- 14709622
TI  - CYP3A induction by liver x receptor ligands in primary cultured rat and mouse
      hepatocytes is mediated by the pregnane X receptor.
AB  - The effects of oxysterol and drug ligands of the liver X receptor (LXR) on
      cytochrome P450 expression were evaluated in primary cultured rodent hepatocytes.
      Treatment of rat hepatocyte cultures with either 25-hydroxycholesterol or
      24(S),25-epoxycholesterol (10(-5) to 5 x 10(-5) M) produced concentration
      dependent elevations in CYP3A mRNA and immunoreactive protein levels but did not
      increase the amounts of CYP1A1, CYP2B, or CYP4A gene products. The effects of
      24(S),25-epoxycholesterol on CYP3A content were much greater than were those of
      25-hydroxycholesterol, consistent with the relative abilities of these sterols to
      bind and activate LXR. To understand the mechanistic basis of these observations,
      experiments were performed using primary cultured hepatocytes prepared from
      LXRalpha/beta- or pregnane X receptor (PXR)-null mice. CYP3A mRNA levels were
      increased after treatment with 24(S),25-epoxycholesterol in both wild-type and
      LXR-null mouse hepatocytes. In contrast, neither 24(S),25-epoxycholesterol nor
      either of two additional potent LXR ligands, 22(R)-hydroxycholesterol and N
      (2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1(trifluoromethyl)ethyl
      ]phenyl]-benzenesulfonamide (T0901317), altered CYP3A mRNA levels in hepatocytes
      prepared from PXR-null mice, although these agents induced CYP3A mRNA content in
      wild-type cultures. As evidence that the LXR ligands also activated PXR in rat
      hepatocytes, cotransfection of primary cultures with a dominant negative PXR
      abolished reporter gene induction after treatment with any of the test agents.
      These results indicate that selected LXR ligands are capable of activating PXR,
      probably as a defensive measure to prevent the accumulation of these potentially
      toxic endogenous molecules.

PMID- 14709623
TI  - Characterization of N-glucuronidation of the lung carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in human liver: importance of
      UDP-glucuronosyltransferase 1A4.
AB  - The nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), is one of the most potent and abundant procarcinogens
      found in tobacco and tobacco smoke and is considered to be a causative agent for
      several tobacco-related cancers. Glucuronidation of the major metabolite of NNK,
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), has been implicated as an
      important mechanism for NNK detoxification. To characterize NNAL metabolism by N
      glucuronidation in humans, high-pressure liquid chromatography was used to detect
      glucuronide conjugates of NNAL formed in human liver microsomes in vitro. In
      addition to peaks corresponding to the O-glucuronides of NNAL (NNAL-O-Gluc), a
      second series of peaks were observed in human liver microsomes that were
      identified by liquid chromatography-mass spectrometry to be NNAL N-glucuronides
      (NNAL-N-Gluc). Microsomes prepared from liver specimens from individual subjects
      (n = 42) exhibited substantial variability in the levels of NNAL-N-Gluc (49-fold
      variability) and NNAL-O-Gluc (49-fold variability) formed in vitro. This
      variability was likely not due to differences in tissue quality, as substantial
      variability (5-fold) was also observed in the ratio of NNAL-N-Gluc/NNAL-O-Gluc
      formation, with a mean ratio of 1.7 in the 42 specimens. Liver microsomes from
      smokers (n = 14) exhibited no significant difference in the levels of either NNAL
      N-Gluc or NNAL-O-Gluc formation, or in the ratio of NNAL-N-Gluc/NNAL-O-Gluc
      formation, as compared with liver microsomes from never smokers (n = 28).
      Overexpressed UDP-glucuronosyltransferase (UGT) 1A4 exhibited significant levels
      of N-glucuronidating activity (V(max)/K(m) = 3.11 microl. min(-1). g(-1)) in
      vitro; no NNAL-N-glucuronide formation was detected for the 11 other
      overexpressed UGT enzymes tested in these studies. These results demonstrate the
      importance of N-glucuronidation in the metabolism of NNAL and the role of UGT1A4
      in this pathway.

PMID- 14709624
TI  - The olivacine derivative s 16020 (9-hydroxy-5,6-dimethyl-N-[2
      (dimethylamino)ethyl)-6H-pyrido(4,3-B)-carbazole-1-carboxamide) induces CYP1A and
      its own metabolism in human hepatocytes in primary culture.
AB  - The olivacine derivative 9-hydroxy-5,6-dimethyl-N-[2-(dimethylamino)ethyl)-6H
      pyrido(4,3-b)-carbazole-1-carboxamide (S 16020) exhibits a potent antitumor
      activity. However, when administered in cancer patients, its blood clearance
      increases after repeated administrations, whereas the volume of distribution
      remains constant, suggesting that the drug is able to induce its own metabolism.
      The aim of this work was to identify the enzymes involved in S 16020 metabolism
      and determine whether this molecule is an enzyme inducer in human hepatocytes in
      primary cultures. Among a battery of cDNA-expressed cytochromes P450 (P450s) and
      flavin monooxygenase (FMO), only CYP1A1, CYP1A2, and FMO3 were able to generate
      detectable amounts of metabolites of S 16020. In primary hepatocytes, S 16020
      behaved as a CYP1A inducer, producing an increase in CYP1A2 protein, acetanilide
      4-hydroxylation, ethoxyresorufin O-deethylation, and chlorzoxazone 6
      hydroxylation to an extent similar to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), a prototypical CYP1A inducer. The levels of other P450 proteins,
      including CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2E1, and CYP3A4, and related
      activities were not affected by S 16020. In primary hepatocytes, pretreatment of
      cells with S 16020 or TCDD produced a significant and similar increase of S 16020
      metabolism, consistent with the previous indications on the role of CYP1As. We
      conclude that CYP1As and FMO3 are the major phase I enzymes involved in the
      metabolism of S 16020 and that this molecule is a potent hydrocarbon-like inducer
      able to stimulate its own metabolism in primary human hepatocytes and liver.

PMID- 14709625
TI  - Potent inhibition of human liver aldehyde oxidase by raloxifene.
AB  - The selective estrogen receptor modulator, raloxifene, has been demonstrated as a
      potent uncompetitive inhibitor of human liver aldehyde oxidase-catalyzed
      oxidation of phthalazine, vanillin, and nicotine-Delta1'(5')-iminium ion, with
      K(i) values of 0.87 to 1.4 nM. Inhibition was not time-dependent. Raloxifene has
      also been shown to be a noncompetitive inhibitor of an aldehyde oxidase-catalyzed
      reduction reaction of a hydroxamic acid-containing compound, with a K(i) of 51
      nM. However, raloxifene had only small effects on xanthine oxidase, an enzyme
      related to aldehyde oxidase. In addition, several other compounds of the same
      therapeutic class as raloxifene were examined for their potential to inhibit
      aldehyde oxidase. However, none were as potent as raloxifene, since IC(50) values
      were orders of magnitude higher and ranged from 0.29 to 57 micro M. In an
      examination of analogs of raloxifene, it was shown that the bisphenol structure
      with a hydrophobic group on the 3-position of the benzthiophene ring system was
      the most important element that imparts inhibitory potency. The relevance of
      these data to the mechanistic understanding of aldehyde oxidase catalysis, as
      well as to the potential for raloxifene to cause drug interactions with agents
      for which aldehyde oxidase-mediated metabolism is important, such as zaleplon or
      famciclovir, is discussed.

PMID- 14709626
TI  - Metabolism of opioids is altered in liver microsomes of sickle cell transgenic
      mice.
AB  - Pain in sickle cell anemia (SCA) is clinically managed with opioid analgesics.
      There are reports that SCA patients tolerate high doses of these drugs without
      adequate pain relief. The current study investigated the in vitro hepatic
      metabolism of opioids in mouse models of sickle cell anemia, with the hypothesis
      that higher dose requirements in SCA could be explained by an increased
      metabolism rate of opioids. Various rodent cytochrome P450 substrates, i.e.,
      buprenorphine and codeine, and rodent uridine glucuronosyltransferase substrates,
      i.e., morphine, buprenorphine, and estradiol, were studied. The three groups used
      were: 1) control C57BL mice, 2) mice with the human alpha-globin and sickle beta
      globin transgenes (SC), and 3) mice with the human alpha-globin and sickle beta
      globin transgenes, and homozygous for the murine alpha-globin and heterozygous
      for the beta(major)-gene knockout (SCKO). In vitro hepatic microsomal incubations
      were carried out for each substrate, and data were fit to the Michaelis-Menten
      equation. Morphine formation had a higher V(max) in SCKO microsomes (0.4 +/-
      0.009 nmol/min. mg; estimate +/- S.E.) than controls (0.25 +/- 0.007). Morphine-3
      glucuronide formation had V(max) estimates of 18.9 +/- 0.6, 25.1 +/- 0.4, and
      27.06 +/- 1.1 nmol/min. mg in control, SC, and SCKO microsomes, respectively. The
      control V(max) for estradiol-3-glucuronide formation was 2-fold greater than in
      SCKO microsomes. The control V(max) for estradiol 17-glucuronide formation was
      3.4- and 2.2-fold greater than in SC and SCKO microsomes. Thus, in vitro
      metabolism of opioids is altered in SCA mouse models, which may lead to altered
      clearances of these drugs.

PMID- 14709627
TI  - Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence
      that inhibition is irreversible.
AB  - Azamulin [14-O-(5-(2-amino-1,3,4-triazolyl)thioacetyl)-dihydromutilin] is an
      azole derivative of the pleuromutilin class of antiinfectives. We tested the
      inhibition potency of azamulin toward 18 cytochromes P450 using human liver
      microsomes or microsomes from insect cells expressing single isoforms. In a
      competitive inhibition model, IC(50) values for CYP3A (0.03-0.24 microM) were at
      least 100-fold lower than all other non-CYP3A enzymes except CYP2J2 (
      approximately 50-fold lower). The IC(50) value with heterologously expressed
      CYP3A4 was 15-fold and 13-fold less than those of CYP3A5 and CYP3A7,
      respectively. The reference inhibitor ketoconazole was less selective and
      exhibited potent inhibition (IC(50) values <10 microM) for CYP1A1, CYP1B1,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP4F2, and CYP4F12. Inhibition of CYP3A by
      azamulin appeared sigmoidal and well behaved with the substrates 7-benzyloxy-4
      trifluoromethylcoumarin, testosterone, and midazolam. Preincubation of 4.8 microM
      azamulin in the presence of NADPH for 10 min inhibited approximately 95% of
      testosterone 6beta-hydroxylase activity compared with preincubation in the
      absence of NADPH. Catalytic activities of CYP1A2, CYP2C8, CYP2C9, CYP2C19,
      CYP2D6, and CYP2E1 were unaffected by similar experiments. Incubation of azamulin
      with heterologously expressed CYP3A4 yielded a type I binding spectrum with a
      spectral dissociation constant of 3.5 microM, whereas no interaction was found
      with CYP2D6. Azamulin exhibited good chemical stability when stored in
      acetonitrile for up to 12 days. Aqueous solubility was found to be >300 microM.
      Azamulin represents an important new chemical tool for use in characterizing the
      contribution of CYP3A to the metabolism of xenobiotics.

PMID- 14709628
TI  - Studies on the metabolism of the novel, selective cyclooxygenase-2 inhibitor
      indomethacin phenethylamide in rat, mouse, and human liver microsomes:
      identification of active metabolites.
AB  - The metabolism of 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N
      phenethyl-acetamide (indomethacin phenethylamide, LM-4108), a highly selective
      cyclooxygenase-2 inhibitor, was studied in rat, mouse, and human liver
      microsomes. The primary site of oxidation in all species examined was on the
      methylene carbons of the phenethyl side chain to form the 1'- and 2'-hydroxy and
      2'-oxo metabolites as determined by electrospray ionization liquid chromatography
      tandem mass spectrometry. Half-lives for the disappearance of 10 microM LM-4108
      in rat, human, and mouse liver microsomes (0.15 pmol P450/ml) were 11 min, 21
      min, and 51 min, respectively. Indomethacin formation was not observed in
      incubations with rat, mouse, or human liver microsomes. Both the 2'-hydroxy-LM
      4108 and 2'-oxo-LM-4108 metabolites were synthesized and found to be equipotent
      to the parent compound with regard to COX-2 inhibitory potency and selectivity
      [2'-hydroxy-LM-4108: IC(50)(COX-2) = 0.06 microM, IC(50)(COX-1) >66 microM; 2'
      oxo-LM-4108: IC(50)(COX-2) = 0.05 microM, IC(50)(COX-1) >66 microM]. The
      formation of the metabolites was strongly inhibited by specific CYP3A4 inhibitors
      ketoconazole and troleandomycin but not by other isoform-selective inhibitors.
      These findings were confirmed by demonstrating that cloned, expressed CYP3A4
      catalyzed side chain oxidation. O-Demethylation was a minor oxidative pathway in
      contrast to the metabolism of indomethacin and was catalyzed by CYP2D6. Upon
      intravenous administration of LM-4108 to Sprague-Dawley rats, oxidative
      metabolism on the phenethyl side chain constituted the rate-limiting steps in its
      clearance. The active metabolites, 2'-oxo- and 2'-hydroxy-LM-4108, as well as 1'
      hydroxy-LM-4108, were all observed in rat plasma and thus may contribute to COX-2
      inhibition in vivo. The glucuronides of 2'hydroxy-LM-4108 and O-desmethyl-2'
      hydroxy-LM-4108 were also identified in rat bile.

PMID- 14709629
TI  - Metabolism and mutagenicity of source water contaminants 1,3-dichloropropane and
      2,2-dichloropropane.
AB  - Cytochrome P450-dependent oxidation and glutathione (GSH)-dependent conjugation
      are the primary routes of metabolism of haloalkanes. Using rat liver microsomes
      and cytosol, we investigated the metabolism of two halopropanes found on the U.S.
      Environmental Protection Agency Contaminant Candidate List, 1,3-dichloropropane
      (1,3-DCP) and 2,2-dichloropropane (2,2-DCP). An automated headspace technique
      using gas chromatography was developed to determine rates of metabolism.
      Additional dihaloalkanes (1,2-dichloroethane, 1,2-dichloropropane, 1,4
      dichlorobutane, 1,2-dibromoethane, 1,2-dibromopropane, 1,4-dibromobutane) were
      evaluated to assess structure-activity relationships. In general, brominated
      dihaloalkanes were eliminated from rat cytosol faster than chlorinated
      dihaloalkanes, reflecting the expected halide order of reactivity (Br > Cl).
      Furthermore, the rate of GSH conjugation was proportional to alpha,omega
      haloalkane chain length. The clearance of 1,3-DCP via the GSH conjugation pathway
      (1.6 x 10(-4) l/h/mg cytosol protein) was minor relative to the P450 pathway (2.8
      x 10(-2) l/h/mg microsomal protein). In contrast, we did not observe metabolism
      of 2,2-DCP via the GSH-dependent conjugation pathway and observed only a minor
      level of clearance via the P450 pathway (7 x 10(-4) l/h/mg microsomal protein).
      Neither compound was mutagenic in various strains of Salmonella, including those
      containing GSTT1-1, indicating that GSTT1-1 does not metabolize 1,3-DCP or 2,2
      DCP to mutagens. Analysis of the reaction products of 1,3-DCP and GSH in cytosol
      by liquid chromatography/mass spectrometry revealed significant production of S
      (3-chloropropyl) glutathione conjugate, indicating that the conjugate half
      mustard does not rearrange to form a sulfonium ion, as typically occurs with
      vicinal dihaloalkanes.

PMID- 14709630
TI  - Development of a computational approach to predict blood-brain barrier
      permeability.
AB  - The objectives of this study were to generate a data set of blood-brain barrier
      (BBB) permeability values for drug-like compounds and to develop a computational
      model to predict BBB permeability from structure. The BBB permeability, expressed
      as permeability-surface area product (PS, quantified as logPS), was determined
      for 28 structurally diverse drug-like compounds using the in situ rat brain
      perfusion technique. A linear model containing three descriptors, logD, van der
      Waals surface area of basic atoms, and polar surface area, was developed based on
      23 compounds in our data set, where the penetration across the BBB was assumed to
      occur primarily by passive diffusion. The correlation coefficient (R(2)) and
      standard deviation (S.D.) of the model-predicted logPS against the observed are
      0.74 and 0.50, respectively. If an outlier was removed from the training data
      set, the R(2) and S.D. were 0.80 and 0.44, respectively. This new model was
      tested in two literature data sets, resulting in an R(2) of 0.77 to 0.94 and a
      S.D. of 0.38 to 0.51. For comparison, four literature models, logP, logD, log(D.
      MW(-0.5)), and linear free energy relationship, were tested using the set of 23
      compounds primarily crossing the BBB by passive diffusion, resulting in an R(2)
      of 0.33 to 0.61 and a S.D. of 0.59 to 0.76. In summary, we have generated the
      largest PS data set and developed a robust three-descriptor model that can
      quantitatively predict BBB permeability. This model may be used in a drug
      discovery setting to predict the BBB permeability of new chemical entities.

PMID- 14709631
TI  - An assessment of udp-glucuronosyltransferase induction using primary human
      hepatocytes.
AB  - Uridine diphosphate glucuronosyltransferases (UGTs) catalyze the glucuronidation
      of a wide range of xenobiotics and endogenous substrates. However, there is a
      lack of information concerning the response of human UGTs to inducers, and this
      observation prompted the current investigation. The glucuronidation of estradiol
      (3- and 17-positions), naphthol, propofol, and morphine (3- and 6-positions) was
      assessed against a battery of recombinant human UGTs to determine selective
      glucuronidation reactions for induction studies. The potential induction of the
      glucuronidation of estradiol at the 3-position, naphthol, propofol, and morphine
      at the 3-position was subsequently investigated in cultured primary human
      hepatocytes against a range of prototypic inducers including dexamethasone, 3
      methylcholanthrene (3-MC), phenobarbital, rifampicin, and omeprazole. Treatment
      with 3-MC induced estradiol-3-glucuronidation (up to 2.5-fold) in four of five
      donors investigated. Statistically significant increases in naphthol
      glucuronidation (up to 1.7-fold) were observed following treatment with
      carbamazepine. UGT1A9-mediated propofol glucuronidation was induced by
      phenobarbital (up to 2.2-fold) and rifampicin (up to 1.7-fold). However,
      treatment with alpha-naphthoflavone and tangeretin resulted in a decrease in
      propofol glucuronidation (30% of control values). Statistically significant
      induction of morphine-3-glucuronidation was observed in at least three donors
      following treatment with phenobarbital, rifampicin, and carbamazepine. Each UGT
      isoform investigated displayed a distinct induction profile. Although
      statistically significant increases in glucuronidation were observed for each
      reaction studied, the level of induction was less than that observed for CYP1A2
      or CYP3A4 and exhibited a large interdonor variability. The clinical relevance of
      the induction responses obtained in this study is unclear.

PMID- 14709632
TI  - Functional characterization of four naturally occurring variants of human
      pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding
      activity and the transactivation of the CYP3A4 promoter/enhancer region.
AB  - Metabolism of administered drugs is determined by expression and activity of many
      drug-metabolizing enzymes, such as the cytochrome P450 (P450s) family members.
      Pregnane X receptor (PXR) is a master transcriptional regulator of many
      drug/xenobiotic-metabolizing enzymes, including P450s and drug transporters. In
      this study, we describe the functional analysis of four naturally occurring human
      PXR (hPXR) variants (R98C, R148Q, R381W, and I403V) that we have recently
      identified. By a reporter gene assay using the CYP3A4 promoter/enhancer reporter
      in COS-7 or HepG2 cells, it was found that the R98C variant failed to
      transactivate the CYP3A4 reporter. The R381W and I403V variants also showed
      varying degrees of reduction in transactivation, depending on the dose of PXR
      activators, rifampicin, clotrimazole, and paclitaxel. The transcriptional
      activities of the R148Q variant were not significantly different from that of the
      wild-type hPXR. The electrophoretic mobility shift assay revealed that only the
      R98C variant lacked DNA binding. Furthermore, the cellular localization of the
      hPXR proteins was analyzed. All four variants as well as the wild-type hPXR
      localized exclusively to the nucleus, regardless of the presence or absence of
      rifampicin. These data suggest that the R98C, R381W, and I403V hPXR variants,
      especially R98C, may influence the expression of drug-metabolizing enzymes and
      transporters, which are transactivated by PXR.

PMID- 14709635
TI  - Facts and recommendations about total homocysteine determinations: an expert
      opinion.
AB  - BACKGROUND: Measurement of plasma total homocysteine has become common as new
      methods have been introduced. A wide range of disorders are associated with
      increased concentrations of total homocysteine. The purpose of this review is to
      provide an international expert opinion on the practical aspects of total
      homocysteine determinations in clinical practice and in the research setting and
      on the relevance of total homocysteine measurements as diagnostic or screening
      tests in several target populations. METHODS: Published data available on Medline
      were used as the basis for the recommendations. Drafts of the recommendations
      were critically discussed at meetings over a period of 3 years. OUTCOME: This
      review is divided into two sections: (a) determination of homocysteine (methods
      and their performance, sample collection and handling, biological determinants,
      reference intervals, within-person variability, and methionine loading test); and
      (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin
      deficiencies, cardiovascular disease, renal failure, psychiatric disorders and
      cognitive impairment, pregnancy complications and birth defects, and screening of
      elderly and newborns). Each of these subsections concludes with a separate series
      of recommendations to assist the clinician and the research scientist in making
      informed decisions. The review concludes with a list of unresolved questions.

PMID- 14709633
TI  - Topological changes in the CYP3A4 active site probed with phenyldiazene: effect
      of interaction with NADPH-cytochrome P450 reductase and cytochrome b5 and of site
      directed mutagenesis.
AB  - The active site topology of heterologously expressed CYP3A4 purified from an
      Escherichia coli expression system was examined using phenyldiazene. Incubation
      of CYP3A4 with phenyldiazene and subsequent oxidation yielded all four potential
      N-phenylprotoporphyrin IX regioisomers derived from attack on an available
      nitrogen atom in pyrrole rings B, A, C, or D (N(B):N(A):N(C):N(D) = 6:73:7: 13).
      Further study using 28 active site mutants showed that substitution of residues
      closer to the heme, Ala-305, Thr-309, or Ala-370, with a larger residue caused
      the most drastic changes in regioisomer formation, which reflected the location
      of each amino acid residue replaced in a CYP3A4 homology model. Previous studies
      have suggested a conformational change in CYP3A4 upon binding of NADPH-cytochrome
      P450 reductase (CPR) or cytochrome b(5) (b(5)). Therefore, regioisomer formation
      was also compared in the absence of redox partners and in the presence of CPR,
      b(5), or both. Formation of all four regioisomers in CYP3A4 wild type,
      particularly the minor ones, was reduced in the presence of b(5). CPR also
      greatly decreased the three minor isomers but increased the major isomer
      significantly. The presence of b(5) and CPR restored minor isomer formation and
      suppressed the enhancement of N(A) formation caused by CPR alone. Interestingly,
      the effects of the redox partners differed among representative active site
      mutants. In particular, the increase in N(C) upon substitution of Ala-370 with
      Phe was significantly reversed in the presence of redox partners, strongly
      suggesting that a conformational change occurs around pyrrole ring C due to
      protein-protein interactions between CYP3A4 and CPR or b(5).

PMID- 14709636
TI  - Immuno-PCR for detection of antigen to Angiostrongylus cantonensis circulating
      fifth-stage worms.
AB  - BACKGROUND: Definitive diagnosis of infestation with Angiostrongylus cantonensis
      is difficult because the parasitic nematode is undetectable in the cerebrospinal
      fluid (CSF) of one-half of afflicted patients and the diagnostic sensitivity of
      ELISA for circulating worm antigens in patient sera is low. We studied immuno-PCR
      as a diagnostic tool. METHODS: We studied 30 controls and 60 afflicted patients
      (30 confirmed by parasitologic analysis of CSF). We used a monoclonal antibody to
      capture circulating A. cantonensis antigens in serum samples. A DNA label
      generated by PCR amplification with biotinylated primer was bound by use of
      streptavidin to a biotinylated third antibody. Circulating antigens sandwiched by
      monoclonal antibody were detected by PCR amplification of the DNA label. RESULTS:
      The detection limit of the ELISA was 100-1000 times higher than that of the
      immuno-PCR. The concentrations of circulating antigens in patients were markedly
      higher than those in controls (Wilcoxon rank-sum test, P <0.001). At a cutoff of
      0.1 ng/L, sensitivity and specificity for immunodiagnosis of patients with
      angiostrongyliasis by immuno-PCR were 98% (95% confidence interval, 91-99%) and
      100% (93-100%), respectively. The test was positive in all parasitologically
      confirmed cases. CONCLUSIONS: Immuno-PCR is a promising technique for diagnosis
      of A. cantonensis infestation.

PMID- 14709637
TI  - Detection of SARS coronavirus in patients with severe acute respiratory syndrome
      by conventional and real-time quantitative reverse transcription-PCR assays.
AB  - BACKGROUND: A novel coronavirus (CoV) was recently identified as the agent for
      severe acute respiratory syndrome (SARS). We compared the abilities of
      conventional and real-time reverse transcription-PCR (RT-PCR) assays to detect
      SARS CoV in clinical specimens. METHODS: RNA samples isolated from nasopharyngeal
      aspirate (NPA; n = 170) and stool (n = 44) were reverse-transcribed and tested by
      our in-house conventional RT-PCR assay. We selected 98 NPA and 37 stool samples
      collected at different times after the onset of disease and tested them in a real
      time quantitative RT-PCR specific for the open reading frame (ORF) 1b region of
      SARS CoV. Detection rates for the conventional and real-time quantitative RT-PCR
      assays were compared. To investigate the nature of viral RNA molecules in these
      clinical samples, we determined copy numbers of ORF 1b and nucleocapsid (N) gene
      sequences of SARS CoV. RESULTS: The quantitative real-time RT-PCR assay was more
      sensitive than the conventional RT-PCR assay for detecting SARS CoV in samples
      collected early in the course of the disease. Real-time assays targeted at the
      ORF 1b region and the N gene revealed that copy numbers of ORF 1b and N gene
      sequences in clinical samples were similar. CONCLUSIONS: NPA and stool samples
      can be used for early diagnosis of SARS. The real-time quantitative RT-PCR assay
      for SARS CoV is potentially useful for early detection of SARS CoV. Our results
      suggest that genomic RNA is the predominant viral RNA species in clinical
      samples.

PMID- 14709638
TI  - Beta-thalassemia microelectronic chip: a fast and accurate method for mutation
      detection.
AB  - BACKGROUND: beta-Thalassemia is one of the most common genetic diseases in
      humans. We developed an automated electronic microchip for fast and reliable
      detection of the nine most frequent mutations accounting for >95% of the beta
      thalassemia alleles in the Mediterranean area. METHODS: We developed a microchip
      based assay to identify the nine most frequent mutations (cd39C>T, IVS1-110G>A,
      IVS1-1G>A, IVS1-6T>C, IVS2-745C>G, cd6delA, -87C>G, IVS2-1G>A, and cd8delAA) by
      use of the Nanogen Workstation. The biotinylated amplicon was electronically
      addressed on the chip to selected pads, where it remained embedded through
      interaction with streptavidin in the permeation layer. The DNA at each test site
      was then hybridized to a mixture of fluorescently labeled wild-type or mutant
      probes. RESULTS: Assays conditions were established based on the analysis of 700
      DNA samples from compound heterozygotes or homozygotes for the nine mutations.
      The assays were blindly validated on 250 DNA samples previously genotyped by
      other methods, with complete concordance of results. Alternative multiplexed
      formats were explored: the combination of multiplex PCR with multiple addressing
      and/or hybridization allowed analysis of all nine mutations in the same sample on
      one test site of the chip. CONCLUSIONS: The open flexible platform can be
      designed by the user according to the local prevalence of mutations in each
      geographic area and can be rapidly extended to include the remaining mutations
      causing beta-thalassemia in other regions of the world.

PMID- 14709639
TI  - Size distributions of maternal and fetal DNA in maternal plasma.
AB  - BACKGROUND: The discovery of fetal DNA in maternal plasma has opened up an
      approach for noninvasive prenatal diagnosis. Despite the rapid expansion in
      clinical applications, the molecular characteristics of plasma DNA in pregnant
      women remain unclear. METHODS: We investigated the size distribution of plasma
      DNA in 34 nonpregnant women and 31 pregnant women, using a panel of quantitative
      PCR assays with different amplicon sizes targeting the leptin gene. We also
      determined the size distribution of fetal DNA in maternal plasma by targeting the
      SRY gene. RESULTS: The median percentages of plasma DNA with size >201 bp were
      57% and 14% for pregnant and nonpregnant women, respectively (P <0.001, Mann
      Whitney test). The median percentages of fetal-derived DNA with sizes >193 bp and
      >313 bp were 20% and 0%, respectively, in maternal plasma. CONCLUSION: Plasma DNA
      molecules are mainly short DNA fragments. The DNA fragments in the plasma of
      pregnant women are significantly longer than those in the plasma of nonpregnant
      women, and the maternal-derived DNA molecules are longer than the fetal-derived
      ones.

PMID- 14709640
TI  - Troponin I in patients without chest pain.
AB  - BACKGROUND: Testing for troponin has important clinical value for patients who
      present with typical symptoms of acute coronary syndromes (ACS) such as chest
      pain (CP). Much less is known about the value of troponin testing for patients
      who present with other symptoms of ACS (anginal equivalent symptoms). METHODS:
      The utilization and prognostic value of cardiac troponin I (cTnI) were evaluated
      at a Veterans Affairs Acute Care Facility. Clinical charts of 1184 predominantly
      male patients, who submitted specimens for initial cTnI testing by AxSYM, were
      evaluated for demographic data, cardiovascular risk factors, major diseases, and
      complaints at the time of testing. The endpoint was defined as all-cause death
      during a 200-day period after initial testing. RESULTS: Sixty-one percent of cTnI
      tests were ordered for patients who did not present with CP. Patients presenting
      with symptoms other than CP did not have significantly lower plasma cTnI than
      patients with CP. However, patients with symptoms other than CP were rarely
      diagnosed with ACS unless cTnI was >/=2 microg/L. The mortality during the follow
      up period was severalfold higher among patients presenting with symptoms other
      than CP (CP, 6%; without CP, 22%; P <0.0001, chi(2) test). cTnI >/=0.2 microg/L
      provided significant additional predictive information for patients who presented
      with anginal equivalent symptoms such as shortness of breath or general weakness.
      CONCLUSION: Patients with anginal equivalent symptoms of ACS and low-positive
      cTnI are less often diagnosed with ACS and have a higher mortality than patients
      with CP.

PMID- 14709641
TI  - Light-induced byproducts of vitamin C in multivitamin solutions.
AB  - BACKGROUND: When solutions of multivitamin preparations (MVPs) are exposed to
      light, H(2)O(2) as well as organic peroxides are generated and the concentration
      of vitamin C decreases. The aim of this study was to determine, using mass
      spectrometry, whether the generation of oxidative byproducts of vitamin C, such
      as dehydroascorbate (DHA) and 2,3-diketogulonic acid (DKG), accounted for the
      reported decrease in ascorbic acid in MVPs exposed to light. METHODS: Mass
      spectrometry was used to document the formation of byproducts of ascorbic acid in
      solutions containing a MVP, vitamin C + riboflavin, and vitamin C + H(2)O(2) +
      Fe(2+). The involvement of ascorbic acid and H(2)O(2) in the formation of organic
      peroxides was tested by measuring peroxide concentrations in solutions containing
      H(2)O(2) with or without ascorbic acid and with or without Fe(2+) before and
      after addition of catalase. RESULTS: The loss of ascorbic acid in photo-exposed
      MVPs was associated with the concomitant generation of byproducts different from
      DHA and DKG. Among them, one mass fingerprint was particularly observed with
      solutions of vitamin C + riboflavin exposed to ambient light as well as with the
      solution of vitamin C + H(2)O(2) + Fe(2+), suggesting a Fenton-like reaction.
      This fingerprint was associated with the formation of catalase-resistant
      peroxides. CONCLUSION: Exposure of MVPs to light leads to the rapid loss of
      ascorbic acid and generation of specific byproducts that differ from DHA and DKG.
      The conversion of vitamin C into byproducts could be of biological importance in
      accounting for the decrease in ascorbic acid concentrations and the generation of
      organic peroxides in light-exposed MVPs.

PMID- 14709642
TI  - Sensitivity of whole-blood T lymphocytes in individual patients to tacrolimus (FK
      506): impact of interleukin-2 mRNA expression as surrogate measure of
      immunosuppressive effect.
AB  - BACKGROUND: To optimize immunosuppressive treatment in individual transplant
      patients, functional measurements of the effects of tacrolimus (FK 506) are of
      clinical importance. Previous investigations have demonstrated the occurrence of
      tacrolimus-resistant production of interleukin-2 (IL-2) in vitro, which may
      explain in part why rejection episodes are still a frequent problem despite
      attainment of therapeutic blood concentrations and HLA matching. However, an
      adequate surrogate marker to define the tacrolimus response in individual
      patients has not been established. METHODS: We investigated the immunosuppressive
      effects of tacrolimus on anti-CD3/anti-CD28 T-cell costimulation in a human whole
      blood assay, analyzing T-cell proliferation, activation marker expression (CD25,
      CD69), IL-2 protein expression, and cytokine mRNA expression in vitro (n = 11
      healthy individuals). We also quantified IL-2 mRNA expression in patients
      undergoing tacrolimus (n = 4) or cyclosporin A (CsA; n = 4) monotherapy before ex
      vivo living-donor kidney transplantation. RESULTS: T-cell proliferation; CD25,
      CD69, and IL-2 concentrations; and IL-4 mRNA were significantly decreased in
      vitro. In contrast, cytokine mRNA profiles revealed variable tacrolimus
      sensitivity. Whole-blood samples from 3 of 11 healthy individuals demonstrated
      marked suppression of IL-2 mRNA expression (>50%) when tacrolimus was
      administered in vitro. When CsA was added to whole-blood cultures, the influence
      on IL-2 mRNA expression was comparable to that of tacrolimus in 9 of 11
      individuals. Two individuals responded conversely, indicating that differences in
      the in vitro response to tacrolimus and CsA among individuals may be attributable
      to potential heterogeneity in the involvement of the CD28 pathway. Kinetic
      profiles of IL-2 mRNA expression also revealed individually distinct degrees of
      calcineurin inhibitor sensitivity in patients undergoing tacrolimus or CsA
      monotherapy before living-donor kidney transplantation. CONCLUSIONS: Our results
      suggest an individual degree of calcineurin inhibitor sensitivity of activated
      whole-blood lymphocytes based on IL-2 mRNA expression. Our approach is
      potentially valuable for identifying transplant patients in whom IL-2 mRNA
      expression is unaffected or even enhanced after initiation of immunosuppressive
      therapy. Such individuals may be less sensitive to the immunosuppressive agent
      and therefore at increased risk of transplant rejection. Prospective studies are
      necessary to determine the correlation of IL-2 mRNA expression with the clinical
      risk of transplant rejection.

PMID- 14709643
TI  - Immunoassay of estradiol: unanticipated suppression by unconjugated estriol.
AB  - BACKGROUND: Accurate measurement of estradiol is important in clinical settings.
      The quality of laboratory estimations of estradiol may be assessed through
      external quality-assurance surveys. METHODS: Estradiol was measured by
      microparticle enzyme immunoassay (MEIA) and other immunoassays. Proficiency
      testing of medical laboratories was conducted using samples prepared from normal
      male human serum supplemented with exogenous estradiol and other steroid and
      nonsteroid hormones, and participant laboratories measured estradiol by a variety
      of commonly used immunoassay techniques. RESULTS: The imprecision (CV) for
      measurement of estradiol [100-300 ng/L (367-1102 pmol/L)] was </=22% for most
      analytical techniques. Greater imprecision, as high as 40% for the same
      concentration range, was observed for the (AxSYM) MEIA method in the proficiency
      testing event of September 2001. Results from this method were bimodal in
      distribution. We found that unconjugated estriol at concentrations >1.5 microg/L
      (>5.2 nmol/L) interfered with the MEIA method, leading to decreased recovery of
      added estradiol by up to 50%. This suppression in estradiol measurement was
      prevented by dilution of the specimen before measurement. Addition of
      unconjugated estriol gave a positive bias in some other immunoassay methods for
      estradiol. Poor comparability among the immunoassay methods for measurement of
      estradiol at clinically relevant concentrations [ approximately 60 ng/L (220
      pmol/L)] was revealed. CONCLUSIONS: A negative interference of unconjugated
      estriol with the MEIA method is a source of error for estradiol measurement. Lack
      of specificity and lack of comparability among immunoassay methods for estradiol
      may have detrimental effects on medical practice.

PMID- 14709644
TI  - IFCC reference system for measurement of hemoglobin A1c in human blood and the
      national standardization schemes in the United States, Japan, and Sweden: a
      method-comparison study.
AB  - BACKGROUND: The national programs for the harmonization of hemoglobin (Hb)A(1c)
      measurements in the US [National Glycohemoglobin Standardization Program (NGSP)],
      Japan [Japanese Diabetes Society (JDS)/Japanese Society of Clinical Chemistry
      (JSCC)], and Sweden are based on different designated comparison methods (DCMs).
      The future basis for international standardization will be the reference system
      developed by the IFCC Working Group on HbA(1c) Standardization. The aim of the
      present study was to determine the relationships between the IFCC Reference
      Method (RM) and the DCMs. METHODS: Four method-comparison studies were performed
      in 2001-2003. In each study five to eight pooled blood samples were measured by
      11 reference laboratories of the IFCC Network of Reference Laboratories, 9
      Secondary Reference Laboratories of the NGSP, 3 reference laboratories of the
      JDS/JSCC program, and a Swedish reference laboratory. Regression equations were
      determined for the relationship between the IFCC RM and each of the DCMs.
      RESULTS: Significant differences were observed between the HbA(1c) results of the
      IFCC RM and those of the DCMs. Significant differences were also demonstrated
      between the three DCMs. However, in all cases the relationship of the DCMs with
      the RM were linear. There were no statistically significant differences between
      the regression equations calculated for each of the four studies; therefore, the
      results could be combined. The relationship is described by the following
      regression equations: NGSP-HbA(1c) = 0.915(IFCC-HbA(1c)) + 2.15% (r(2) = 0.998);
      JDS/JSCC-HbA(1c) = 0.927(IFCC-HbA(1c)) + 1.73% (r(2) = 0.997); Swedish-HbA(1c) =
      0.989(IFCC-HbA(1c)) + 0.88% (r(2) = 0.996). CONCLUSION: There is a firm and
      reproducible link between the IFCC RM and DCM HbA(1c) values.

PMID- 14709645
TI  - Online measurement of urea concentration in spent dialysate during hemodialysis.
AB  - BACKGROUND: We describe online optical measurements of urea in the effluent
      dialysate line during regular hemodialysis treatment of several patients.
      Monitoring urea removal can provide valuable information about dialysis
      efficiency. METHODS: Spectral measurements were performed with a Fourier
      transform infrared spectrometer equipped with a flow-through cell. Spectra were
      recorded across the 5000-4000 cm(-1) (2.0-2.5 microm) wavelength range at 1-min
      intervals. Savitzky-Golay filtering was used to remove baseline variations
      attributable to the temperature dependence of the water absorption spectrum. Urea
      concentrations were extracted from the filtered spectra by use of partial least
      squares regression and the net analyte signal of urea. RESULTS: Urea
      concentrations predicted by partial least-squares regression matched
      concentrations obtained from standard chemical assays with a root mean square
      error of 0.30 mmol/L (0.84 mg/dL urea nitrogen) over an observed concentration
      range of 0-11 mmol/L. The root mean square error obtained with the net analyte
      signal of urea was 0.43 mmol/L with a calibration based only on a set of pure
      component spectra. The error decreased to 0.23 mmol/L when a slope and offset
      correction were used. CONCLUSIONS: Urea concentrations can be continuously
      monitored during hemodialysis by near-infrared spectroscopy. Calibrations based
      on the net analyte signal of urea are particularly appealing because they do not
      require a training step, as do statistical multivariate calibration procedures
      such as partial least-squares regression.

PMID- 14709647
TI  - The interleukin-6 G(-174)C promoter polymorphism does not determine plasma
      interleukin-6 concentrations in experimental endotoxemia in humans.
AB  - BACKGROUND: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an
      essential role in the pathogenesis of acute and chronic infections. As the role
      of the IL-6 G(-174)C polymorphism in determining serum concentrations of IL-6 is
      controversial, we studied the genotype-specific IL-6 response in a well
      standardized model of systemic inflammation. METHODS: A total of 76 healthy young
      males (age range, 19-35 years) received a single bolus of 2 ng/kg endotoxin
      [lipopolysaccharide (LPS)] intravenously. Plasma IL-6 was measured by enzyme
      immunoassay at 0, 2, 6, and 24 h after LPS infusion, and the IL-6 promoter
      genotype was analyzed by a mutagenic separated PCR assay. RESULTS: IL-6 increased
      300-fold 2 h after LPS challenge and returned almost to normal within 24 h.
      Neither basal IL-6 nor the IL-6 response to LPS was significantly affected by the
      IL-6 promoter genotype. CONCLUSIONS: The IL-6 G(-174)C promoter polymorphism does
      not significantly influence basal concentrations of IL-6 or peak IL-6 in human
      endotoxemia.

PMID- 14709646
TI  - Invasive trophoblast antigen (hyperglycosylated human chorionic gonadotropin) in
      second-trimester maternal urine as a marker for down syndrome: preliminary
      results of an observational study on fresh samples.
AB  - BACKGROUND: Down syndrome screening is commonly performed in the US using
      maternal age and three or four second-trimester maternal serum markers that can
      identify up to 75% of affected pregnancies by offering diagnostic studies to 5%
      of women. Invasive trophoblast antigen [ITA; hyperglycosylated human chorionic
      gonadotropin (hCG)] is a promising marker that can be measured in urine or serum
      in the first or second trimester. We report preliminary results for urinary ITA
      in an ongoing observational study. METHODS: Women undergoing second-trimester
      amniocentesis for reasons not associated with biochemical testing provided
      consent and a urine (and possibly serum) sample that was tested within a few
      days. Demographic and pregnancy-related information was collected, along with
      karyotype. Screening performance was modeled for ITA alone and in combination
      with serum markers RESULTS: Twelve recruitment centers collected urine from 2055
      women with singleton pregnancies between 15 and 20 weeks of gestation (2023
      unaffected, 28 Down syndrome, and 4 pregnancies with other chromosome
      abnormalities). After correction for gestational age, urine concentration, and
      maternal race and weight, the ITA measurements were higher in women with a Down
      syndrome pregnancy (median ITA, 4.33 multiples of the median). At a 75% detection
      rate, the false-positive rate could be reduced by substituting ITA for hCG
      measurements (from 5.6% to 2.6% for the triple test) or by adding ITA
      measurements to existing combinations (from 3.3% to 2.0% for the quadruple test).
      CONCLUSIONS: Our data provide preliminary confirmation of the potential
      usefulness of urinary ITA measurements in detecting Down syndrome in a setting
      that simulates routine usage.

PMID- 14709648
TI  - Simplified HPLC method for urinary and circulating creatinine.

PMID- 14709649
TI  - Multiplex single-nucleotide primer extension analysis to simultaneously detect
      eleven BRCA1 mutations in breast cancer families.

PMID- 14709650
TI  - Effects of filtration on glyceraldehyde-3-phosphate dehydrogenase mRNA in the
      plasma of trauma patients and healthy individuals.

PMID- 14709651
TI  - Effects of concentration and temperature on the stability of nevirapine in whole
      blood and serum.

PMID- 14709652
TI  - Preferential isolation of fragmented DNA enhances the detection of circulating
      mutated k-ras DNA.

PMID- 14709653
TI  - Plasma mitochondrial DNA concentrations after trauma.

PMID- 14709654
TI  - Testing for anti-human transglutaminase antibodies in saliva is not useful for
      diagnosis of celiac disease.

PMID- 14709655
TI  - Evaluation of an enzyme immunometric assay to measure serum adiponectin
      concentrations.

PMID- 14709657
TI  - Measurement of 20-hydroxyeicosatetraenoic acid in human urine by gas
      chromatography-mass spectrometry.

PMID- 14709656
TI  - Proteinuria and hypertension are independent factors affecting fetal DNA values:
      a retrospective analysis of affected and unaffected patients.

PMID- 14709658
TI  - Rapid genotyping for tumor necrosis factor-alpha (TNF-alpha)-863C/A promoter
      polymorphism that determines TNF-alpha response.

PMID- 14709659
TI  - Effect of thyroxine replacement on creatinine, insulin-like growth factor 1, acid
      labile subunit, and vascular endothelial growth factor.

PMID- 14709660
TI  - Genomic sequencing of a SARS coronavirus isolate that predated the Metropole
      Hotel case cluster in Hong Kong.

PMID- 14709661
TI  - Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in
      human plasma.

PMID- 14709662
TI  - Quantification of 5,6-dihydrouracil by HPLC-electrospray tandem mass
      spectrometry.

PMID- 14709663
TI  - Vitamin B12 status in the elderly as judged by available biochemical markers.

PMID- 14709664
TI  - Immediate availability of C-reactive protein and leukocyte count data influenced
      physicians' decisions to prescribe antimicrobial drugs for new outpatients with
      acute infections.

PMID- 14709665
TI  - Quantitative tissue factor gene expression analysis in whole blood: development
      and evaluation of a real-time PCR platform.

PMID- 14709666
TI  - Sequencing: not always the "gold standard".

PMID- 14709667
TI  - S100B protein in clinical diagnostics: assay specificity.

PMID- 14709668
TI  - Multicenter characterization and validation of the intron-8 poly(T) tract (IVS8
      T) status in 25 Coriell cell repository cystic fibrosis reference cell lines for
      cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation assays.

PMID- 14709669
TI  - Artifactual undetectable HDL-cholesterol with the Beckman synchron LX and vitros
      950 assays temporally associated with a paraprotein.

PMID- 14709670
TI  - EDTA is a better anticoagulant than heparin or citrate for delayed blood
      processing for plasma DNA analysis.

PMID- 14709671
TI  - Cross-reactivity of three recombinant insulin analogs with five commercial
      insulin immunoassays.

PMID- 14709673
TI  - The Arabidopsis LUT1 locus encodes a member of the cytochrome p450 family that is
      required for carotenoid epsilon-ring hydroxylation activity.
AB  - Lutein, a dihydroxy xanthophyll, is the most abundant carotenoid in plant
      photosynthetic tissues and plays crucial structural and functional roles in the
      light-harvesting complexes. Carotenoid beta-and epsilon-hydroxylases catalyze the
      formation of lutein from alpha-carotene (beta,epsilon-carotene). In contrast to
      the well studied beta-hydroxylases that have been cloned and characterized from
      many organisms, the epsilon-hydroxylase has only been genetically defined by the
      lut1 mutation in Arabidopsis. We have isolated the LUT1 gene by positional
      cloning and found that, in contrast to all known carotenoid hydroxylases, which
      are the nonheme diiron monooxygenases, LUT1 encodes a cytochrome p450-type
      monooxygenase, CYP97C1. Introduction of a null mutant allele of LUT1, lut1-3,
      into the beta-hydroxylase 1/beta-hydroxylase 2 (b1 b2) double-mutant background,
      in which both Arabidopsis beta-hydroxylases are disrupted, yielded a genotype
      (lut1-3 b1 b2) in which all three known carotenoid hydroxylase activities are
      eliminated. Surprisingly, hydroxylated beta-rings were still produced in lut1-3
      b1 b2, suggesting that a fourth unknown carotenoid beta-hydroxylase exists in
      vivo that is structurally unrelated to beta-hydroxylase 1 or 2. A second
      chloroplast-targeted member of the CYP97 family, CYP97A3, is 49% identical to
      LUT1 and hypothesized as a likely candidate for this additional beta-ring
      hydroxylation activity. Overall, LUT1 defines a class of carotenoid hydroxylases
      that has evolved independently from and uses a different mechanism than nonheme
      diiron beta-hydroxylases.

PMID- 14709674
TI  - DNA nanotubes self-assembled from triple-crossover tiles as templates for
      conductive nanowires.
AB  - DNA-based nanotechnology is currently being developed as a general assembly
      method for nanopatterned materials that may find use in electronics, sensors,
      medicine, and many other fields. Here we present results on the construction and
      characterization of DNA nanotubes, a self-assembling superstructure composed of
      DNA tiles. Triple-crossover tiles modified with thiol-containing double-stranded
      DNA stems projected out of the tile plane were used as the basic building blocks.
      Triple-crossover nanotubes display a constant diameter of approximately 25 nm and
      have been observed with lengths up to 20 microm. We present high-resolution
      images of the constructs, experimental evidence of their tube-like nature as well
      as data on metallization of the nanotubes to form nanowires, and electrical
      conductivity measurements through the nanowires. DNA nanotubes represent a
      potential breakthrough in the self-assembly of nanometer-scale circuits for
      electronics layout because they can be targeted to connect at specific locations
      on larger-scale structures and can subsequently be metallized to form nanometer
      scale wires. The dimensions of these nanotubes are also perfectly suited for
      applications involving interconnection of molecular-scale devices with macroscale
      components fabricated by conventional photolithographic methods.

PMID- 14709675
TI  - Global gene repression by KaiC as a master process of prokaryotic circadian
      system.
AB  - A kaiABC clock gene cluster was previously identified from cyanobacterium
      Synechococcus elongatus PCC 7942, and the feedback regulation of kai genes was
      proposed as the core mechanism generating circadian oscillation. In this study,
      we confirmed that the Kai-based oscillator is the dominant circadian oscillator
      functioning in cyanobacteria. We probed the nature of this regulation and found
      that excess KaiC represses not only kaiBC but also the rhythmic components of all
      genes in the genome. This result strongly suggests that the KaiC protein
      primarily coordinates genomewide gene expression, including its own expression.
      We also found that a promoter derived from E. coli is feedback controlled by KaiC
      and restores the complete circadian rhythm in kaiBC-inactivated arrhythmic
      mutants, provided it can express kaiB and kaiC genes at an appropriate level.
      Unlike eukaryotic models, specific regulation of the kaiBC promoter is not
      essential for cyanobacterial circadian oscillations.

PMID- 14709676
TI  - Traffic-based feedback on the web.
AB  - Usage data at a high-traffic web site can expose information about external
      events and surges in popularity that may not be accessible solely from analyses
      of content and link structure. We consider sites that are organized around a set
      of items available for purchase or download, consider, for example, an e-commerce
      site or collection of online research papers, and we study a simple indicator of
      collective user interest in an item, the batting average, defined as the fraction
      of visits to an item's description that result in an acquisition of that item. We
      develop a stochastic model for identifying points in time at which an item's
      batting average experiences significant change. In experiments with usage data
      from the Internet Archive, we find that such changes often occur in an abrupt,
      discrete fashion, and that these changes can be closely aligned with events such
      as the highlighting of an item on the site or the appearance of a link from an
      active external referrer. In this way, analyzing the dynamics of item popularity
      at an active web site can help characterize the impact of a range of events
      taking place both on and off the site.

PMID- 14709677
TI  - Rat model of familial combined hyperlipidemia as a result of comparative mapping.
AB  - Total genome scan was carried out in 266 F2 intercrosses from the Prague
      hypertriglyceridemic (HTG) rat that shares several clinical characteristics with
      human metabolic syndrome. Two loci for plasma triglycerides (TG) were localized
      on chromosome 2 (Chr 2) (LOD 4.4, 3.2). The first locus overlapped with the rat
      syntenic region of the human locus for the metabolic syndrome and for small,
      dense LDL, while the second overlapped with the syntenic region of another locus
      for small, dense LDL in humans by the comparative mapping approach. Loci for TG
      on rat Chr 13 (LOD 3.3) and Chr 1 (LOD 2.7) overlapped with the syntenic region
      of loci for human familial combined hyperlipidemia (FCHL) in Finnish and Dutch
      populations, respectively. The concordances of loci for TG localized in this
      study with previously reported loci for FCHL and its related phenotypes are
      underlying the generalized importance of these loci in dyslipidemia. These data
      suggest the close relationship between dyslipidemia in HTG rats and human FCHL,
      establishing a novel animal model for exploration of pathophysiology and therapy
      based on genomic determinants.

PMID- 14709678
TI  - Differential expression of the closely linked KISS1, REN, and FLJ10761 genes in
      transgenic mice.
AB  - We previously reported the development and characterization of transgenic mice
      containing a large 160-kb P1 artificial chromosome (PAC) encompassing the renin
      (REN) locus from human chromosome 1. Here we demonstrate that PAC160 not only
      encodes REN, but also complete copies of the next upstream (KISS1) and downstream
      (FLJ10761) gene along human chromosome 1. Incomplete copies of the second
      upstream (PEPP3) and downstream (SOX13) genes are also present. The gene order
      PEPP3-KISS1-REN-FLJ10761-SOX13 is conserved in mice containing either one or two
      copies of the REN locus. Despite the close localization of KISS1, REN, and
      FLJ10761, they each exhibit distinct, yet overlapping tissue-specific expression
      profiles in humans. The tissue-specific expression patterns of REN and FLJ10761
      were retained in transgenic mice containing PAC160. Expression of REN and
      FLJ10761 were also proportional to copy number. Expression of KISS1 in PAC160
      mice showed both similarities and differences to humans. These data suggest that
      expression of gene blocks encoded on large genomic clones are retained when the
      clones are used to generate transgenic mice. Genomic elements which act to
      insulate genes from their neighbors are also apparently retained.

PMID- 14709679
TI  - Metal ligand affinity pipettes and bioreactive alkaline phosphatase probes: tools
      for characterization of phosphorylated proteins and peptides.
AB  - An alkaline phosphatase-bioreactive probe, in which the enzyme is covalently
      bound to the mass spectrometry target, has been developed for studies of
      phosphoproteins. The bioreactive probe was used in combination with affinity
      capture and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry to study hydrolysis of several phosphoproteins found in human
      saliva. Human salivary proteins were extracted from diluted human saliva with
      immobilized metal-affinity pipettes, which under defined conditions bound the
      phosphoproteins of interest preferentially over histatins. Phosphoproteins were
      eluted directly from the affinity pipettes to the bioreactive probe with diluted
      ammonium hydroxide, which provided conditions appropriate for hydrolysis by the
      alkaline phosphatase covalently bound to the probe surface. Results indicate the
      combination of metal-affinity pipette extraction, alkaline phosphatase
      bioreactive probes, and matrix-assisted laser desorption/ionization mass
      spectrometry is an effective way to find and characterize phosphoproteins, known
      and unknown, in complex mixtures. Facile hydrolysis of human salivary
      phosphoproteins by the bioreactive probes was readily observed.

PMID- 14709680
TI  - When urokinase was gone: commentary on another year of thrombolysis without
      urokinase.

PMID- 14709681
TI  - Development of a research agenda for interventional oncology: proceedings from an
      interdisciplinary consensus panel.

PMID- 14709682
TI  - Catheter-directed thrombolytic therapy for limb ischemia: current status and
      controversies.
AB  - Absence of urokinase from the United States market for the past 4 years has
      resulted in increasing experience with other plasminogen activators in catheter
      directed thrombolytic therapy. The differences in the pharmacologic properties
      and biologic behavior of these agents may translate into clinical outcomes that
      are distinct. Some of these manifestations can be predicted based on the existing
      large clinical trials in the acute myocardial infarction literature. However,
      because of the fundamental differences in techniques and thrombolytic regimens,
      extrapolation of the coronary data may not always predict the performance of
      these agents in peripheral catheter-directed fibrinolysis. In this article, the
      current status of the available lytic agents in the treatment of limb ischemia is
      reviewed.

PMID- 14709684
TI  - Ultrasonographic modalities to assess vascular anatomy and disease.
AB  - Medical ultrasound (US) encompasses a family of imaging techniques linked by the
      use of high-frequency sound waves, typically 2.5-10 million cycles per second
      (MHz), to interrogate tissue. Although similar, each imaging technique has
      relatively distinct features and may provide unique information. This review is
      designed to provide vascular and interventional radiologists with an in-depth
      understanding of each US imaging technique and relevant physics principles to
      assist in optimizing the US examination so that the specific vascular anatomy and
      disease states in question can be comprehensively understood. This review will be
      limited to principles of transcutaneous US and will not include specific
      techniques for assessment of individual vessels (except for illustrative
      purposes) or methods to optimize US scan parameters.

PMID- 14709685
TI  - Efficacy and safety of reteplase for central venous catheter occlusion in
      patients with cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of reteplase for central venous
      catheter (CVC) occlusion in patients with cancer. MATERIALS AND METHODS: An open
      label, single-arm, prospective study was conducted. Reteplase (0.4 U) was
      instilled into each catheter lumen with a dwell time of 30 minutes in patients
      with cancer with a dysfunctional CVC. If the function of the catheter was not
      restored in 30 minutes, an additional dwell time of 30 minutes was allowed (a
      total of 60 minutes possible dwell time for the first dose). A second dose was
      repeated at 60 minutes after the first dose if catheter function was not restored
      (a total of 120 minutes for up to two doses). The primary efficacy outcome was
      the restoration of CVC function. RESULTS: Of 139 patients who received reteplase,
      the first-attempt success rate after a 30-minute dwell time was 66.9%. The
      cumulative success rates at 60, 90, and 120 minutes were 88.5%, 94.7%, and 94.7%,
      respectively. The variation of patient age, catheter age, CVC occlusion age, CVC
      type, number of lumen, or occlusion type was not associated with the efficacy of
      reteplase. There were no treatment-associated adverse events reported during the
      study period. CONCLUSION: Reteplase at 0.4-U dosing per catheter lumen is an
      effective and safe alternative that rapidly restores the patency of occluded CVCs
      in patients with cancer.

PMID- 14709686
TI  - Alteplase for treatment of occluded peripherally inserted central catheters:
      safety and efficacy in 240 patients.
AB  - PURPOSE: Peripherally inserted central catheters (PICCs) have dramatically
      improved intravenous therapy, but thrombotic occlusion remains a common problem.
      Despite the popularity of PICCs, there are few prospective data on the use of
      fibrinolytic agents to salvage these particular devices. The purpose of this
      study was to evaluate the efficacy and safety of alteplase treatment. MATERIALS
      AND METHODS: A subgroup analysis was performed from a phase IIIB prospective,
      multicenter trial of 995 patients evaluating the use of alteplase to restore
      function in occluded venous catheters. Two hundred forty patients (126 men; mean
      age, 53.5 years; range, 2-90 y) with occluded single-lumen (n = 104) or double
      lumen (n = 136) PICCs were identified and constitute the study population.
      Dysfunction was defined as the inability to withdraw 3 mL of blood. Alteplase (2
      mg/2 mL) was instilled into the dysfunctional lumen and assessed at 30 and 120
      minutes. If the lumen remained occluded, a second alteplase dose was instilled
      and assessed at 30 and 120 minutes. Patency was defined as the ability to
      withdraw 3 mL blood and infuse 5 mL of saline solution. The primary efficacy
      endpoint was the cumulative restored patency rate after a maximum of two doses of
      alteplase. The primary safety endpoint was the incidence of intracranial
      hemorrhage within 5 days of treatment. Serious adverse events were recorded for
      30 days after treatment. RESULTS: The primary efficacy endpoint was 92.9% (95%
      CI: 88.8%, 95.8%). Cumulative efficacy 30 and 120 minutes after first and second
      doses were 59.4%, 81.1%, 89.1%, and 92.9%, respectively. The primary safety
      endpoint was 0.0%. One major hemorrhage was reported: a patient with acute flare
      of ulcerative colitis experienced hematochezia 3 days after treatment. One
      serious adverse event (fever) was attributed to study drug. CONCLUSIONS:
      Treatment with use of a maximum of two doses of alteplase is safe and effective
      in restoring function to occluded PICCs.

PMID- 14709688
TI  - Extrinsic compression of the left innominate vein in hemodialysis patients.
AB  - PURPOSE: Central venous stenosis is a common problem in hemodialysis patients.
      The most well known cause is intrinsic stenosis, usually a result of subclavian
      vein catheterization. A lesser-known cause is extrinsic compression of the left
      innominate vein. This study investigates the prevalence of this phenomenon in a
      series of patients undergoing diagnostic fistulography. MATERIALS AND METHODS:
      One hundred six fistulograms of 48 patients were reviewed retrospectively. In
      reviewing the fistulograms, attention was paid to the central veins, which were
      graded for extrinsic compression of the left innominate vein. Presence of
      collaterals was noted, as well as the presence of any intrinsic stenosis of the
      left innominate or subclavian veins. Medical records were reviewed for a history
      of catheterization of the left-side venous system for hemodialysis or any other
      reason. The type of vascular access (native fistula, synthetic graft) and
      indication for the fistulogram were recorded. RESULTS: Some degree of extrinsic
      compression was observed in 21 of 48 of patients (44%). Twelve of 48 patients
      (25%) had mild, six of 48 patients (13%) had moderate and three of 48 patients
      had (6%) severe compression. Among patients with any degree of extrinsic
      compression only four of 21 patients (19%) had previous left subclavian or
      jugular catheterization. Intrinsic stenosis was observed in 11 of 48 patients
      (23%). All but two of them had undergone previous left subclavian or jugular
      catheterization and two had concomitant extrinsic compression. Collaterals were
      seen in 21 of 48 patients (44%). Eleven of 21 patients (52%) with extrinsic
      compression showed collateral veins. Ten of 11 patients (91%) with intrinsic
      stenosis had collateral veins. All three patients with severe extrinsic
      compression were symptomatic and were treated with stent placement after
      angioplasty failed because of elastic recoil. CONCLUSION: Extrinsic compression
      is a common finding on diagnostic hemodialysis fistulography and may be
      hemodynamically significant. Unlike intrinsic stenosis, it is unrelated to
      previous central catheterization. Angioplasty alone may not be adequate for
      treatment and stent placement may be required.

PMID- 14709689
TI  - Do simultaneous bilateral tunneled infusion catheters in patients undergoing bone
      marrow transplantation increase catheter-related complications?
AB  - PURPOSE: Secure venous access with multiple lumens is necessary for the care of
      allogeneic hematopoietic stem cell transplant (HSCT) recipients. The outcomes
      associated with simultaneous bilateral tunneled internal jugular infusion
      catheter placement in the HSCT recipient population were investigated in an
      attempt to determine whether simultaneous introduction of these catheters
      compounds or magnifies the risks (infection, venous thrombosis) associated with
      tunneled catheters. MATERIALS AND METHODS: Patients undergoing HSCT and receiving
      bilateral tunneled infusion catheters in a single procedure were identified using
      a quality assurance data base. Medical records for the duration of
      catheterization were reviewed; 43 patients were included in the study (mean age,
      42 years; range, 22-56). Diagnoses included acute lymphocytic leukemia (n = 4),
      acute myelogenous leukemia (n = 8), aplastic anemia (n = 2), chronic myelogenous
      leukemia (n = 17), chronic lymphocytic leukemia (n = 1), Hodgkin lymphoma (n =
      1), myelodysplasia (n = 4), myelofibrosis (n = 2), and non-Hodgkin lymphoma (n =
      4). Cox proportional hazards regression analysis was performed to determine
      differences in infection rates between dual- and triple-lumen catheters. RESULTS:
      Forty-three pairs of catheters were placed. All met venous access needs for HSCT
      recipient care. Complete follow-up was achieved for 77 of 87 (89%) catheters. The
      overall infection rate was 0.25 per 100 catheter-days. The rate was 0.19 and 0.33
      for dual- and triple-lumen catheters, respectively (P =.15). Mechanical failure
      did not differ between catheter types (dual: 0.14 episodes per 100 days, triple:
      0.05 per 100 days, P =.2). CONCLUSIONS: Bilateral multilumen tunneled infusion
      catheter placement in a single procedure using imaging guidance is safe with
      acceptable outcomes and meets venous access needs for HSCT. There is a trend
      toward higher infection rates, with more lumens and more mechanical failure with
      dual-lumen catheters.

PMID- 14709691
TI  - Percutaneous ablation of VX2 carcinoma-induced liver tumors with use of ethanol
      versus acetic acid: pilot study in a rabbit model.
AB  - PURPOSE: Acetic acid has been employed as a chemical ablation agent for liver
      tumors because of its superior diffusion characteristics compared with ethanol
      and the resulting requirement for smaller volumes and fewer injection sessions.
      Early tissue changes were compared after injection of acetic acid and ethanol in
      a rabbit model of hepatocellular carcinoma. MATERIALS AND METHODS: VX2 tumors
      were created in the left lobe of the liver in 11 male New Zealand White rabbits.
      Each animal underwent a midline minilaparotomy to expose the tumor-laden left
      lobe, followed by injection of 1.0 mL of 100% ethanol (n = 5) or 50% acetic acid
      (n = 6) with use of a 20-gauge infusion needle. Animals were killed 30 minutes
      after surgery; explanted livers were sectioned and examined for gross and
      microscopic changes. RESULTS: Injection of each agent produced rapid diffusion
      through tumor and surrounding hepatic parenchyma, with immediate protein
      precipitation manifested by blanching as a result of coagulation effect. The
      sizes of coagulation zones, expressed as mean products of the maximum
      perpendicular diameters of tumoral diffusion, were 13.0 cm(2) +/- 9.4 and 1.3
      cm(2) +/- 1.8 for acetic acid and ethanol, respectively (P =.049). No differences
      in histologic changes were seen between agents. CONCLUSIONS: In this animal
      model, acetic acid produced significantly larger zones of tumor coagulation
      compared with ethanol when injected into VX2 carcinoma in equal volumes. Further
      evaluation is necessary before these findings can be extrapolated to a clinical
      setting.

PMID- 14709692
TI  - Small intestinal submucosa aneurysm sac embolization for endoleak prevention
      after abdominal aortic aneurysm endografting: a pilot study in sheep.
AB  - PURPOSE: To percutaneously create an improved abdominal aortic aneurysm model of
      endoleak after endograft placement and to explore efficacy of small intestinal
      submucosal embolization of the residual aneurysmal sac for prevention of
      endoleaks. MATERIALS AND METHODS: Abdominal aortic aneurysm was created
      transluminally by over-dilation of a Palmaz stent in 12 sheep. Approximately 20%
      undersized endografts suspended between two stent-graft adapters were used to
      bridge the aneurysm in a manner that two lumbar pairs remained patent within the
      residual aneurysm sac. Size of the residual aneurysm sac was increased by
      placement of an undersized stent-graft consisting of damaged lyophilized small
      intestinal submucosal sheets sandwiched between two Zilver stents. In six sheep,
      residual aneurysm sacs were embolized by combining small intestinal submucosal
      sponge and small intestinal submucosal sheet pieces. The other six sheep served
      as the control group. Angiography performed immediately after the procedure was
      compared with follow-up angiography before the animals were killed at 1, 3, and 7
      months. Gross and histologic examinations were also obtained. RESULTS: Aortic
      ruptures (n = 3) and dissections (n = 2) during aneurysm creation responded well
      to endograft placement. Eleven endografts were placed successfully, one was
      misplaced. The mean diameter of aneurysmal sac was 16 mm in the study and 15.2 mm
      in the control group. In the study group, in four sheep, the sac and seven pairs
      of lumbar arteries were occluded by embolization and remained obstructed by
      organized thrombus during the entire study. There were no type II endoleaks. Four
      type III new endoleaks developed without antegrade filling of lumbar arteries. In
      the control group, five animals had type I and II endoleaks at the initial
      studies. Only one sheep exhibited completely organized thrombosis of the
      aneurysmal sac and without endoleaks. In the other four sheep with partially
      organized sac thrombosis, endoleaks were unchanged. One type III endoleak
      occurred in this group. CONCLUSION: The combination of small intestinal
      submucosal sponge and small intestinal submucosal sheet pieces is a promising
      embolic material for occlusion of the residual sac after endovascular abdominal
      aortic aneurysm repair and for prevention of type II endoleaks.

PMID- 14709693
TI  - Transjugular intrahepatic portosystemic shunt creation as treatment for
      refractory chylous ascites and chylothorax in a patient with cirrhosis.
AB  - The etiology of chylothorax is usually considered to consist of four major
      categories: tumors, trauma, idiopathic conditions, and miscellaneous conditions.
      It appears that chylothorax is a rare and underreported manifestation of
      cirrhosis resulting from transdiaphragmatic passage of chylous ascites. This
      condition can be debilitating as a result of respiratory compromise from a large
      volume of pleural fluid, as well as metabolic derangements, malnutrition, and
      immunologic impairment from loss of vital lymphatic constituents. Herein the
      authors present a case of a 46-year-old male patient with cirrhosis and
      complications of high-volume chylous ascites and chylothorax who was successfully
      treated with creation of a transjugular intrahepatic portosystemic shunt.

PMID- 14709694
TI  - N-butyl cyanoacrylate glue embolization of splenic artery aneurysms.
AB  - A patient with Polyarteritis Nodosa presented with abdominal pain and low
      hematocrit level. Abdominal computed tomography (CT) depicted the presence of
      free blood and CT angiography revealed two aneurysms in the inferior branch of
      the splenic artery that were subsequently treated by endovascular transarterial
      embolization with N-Butyl Cyanoacrylate. Post embolization splenic arteriography
      demonstrated complete embolization of both aneurysms, including the inflow and
      outflow vessels.

PMID- 14709695
TI  - Radiofrequency thermal ablation of hepatic cyst.

PMID- 14709696
TI  - Treatment of renal cell carcinoma-associated dermatomyositis with renal arterial
      embolization and percutaneous radiofrequency heat ablation.

PMID- 14709697
TI  - Misinterpretation of postembolization syndrome after conservative treatment of
      fibroids.

PMID- 14709698
TI  - High living.

PMID- 14709699
TI  - Rudolf Virchow, public health, and the built environment.

PMID- 14709703
TI  - Health and the built environment.

PMID- 14709704
TI  - The built environment and mental health.
AB  - The built environment has direct and indirect effects on mental health. High-rise
      housing is inimical to the psychological well-being of women with young children.
      Poor-quality housing appears to increase psychological distress, but
      methodological issues make it difficult to draw clear conclusions. Mental health
      of psychiatric patients has been linked to design elements that affect their
      ability to regulate social interaction (e.g., furniture configuration, privacy).
      Alzheimer's patients adjust better to small-scale, homier facilities that also
      have lower levels of stimulation. They are also better adjusted in buildings that
      accommodate physical wandering. Residential crowding (number of people per room)
      and loud exterior noise sources (e.g., airports) elevate psychological distress
      but do not produce serious mental illness. Malodorous air pollutants heighten
      negative affect, and some toxins (e.g., lead, solvents) cause behavioral
      disturbances (e.g., self-regulatory ability, aggression). Insufficient daylight
      is reliably associated with increased depressive symptoms. Indirectly, the
      physical environment may influence mental health by altering psychosocial
      processes with known mental health sequelae. Personal control, socially
      supportive relationships, and restoration from stress and fatigue are all
      affected by properties of the built environment. More prospective, longitudinal
      studies and, where feasible, randomized experiments are needed to examine the
      potential role of the physical environment in mental health. Even more
      challenging is the task of developing underlying models of how the built
      environment can affect mental health. It is also likely that some individuals may
      be more vulnerable to mental health impacts of the built environment. Because
      exposure to poor environmental conditions is not randomly distributed and tends
      to concentrate among the poor and ethnic minorities, we also need to focus more
      attention on the health implications of multiple environmental risk exposure.

PMID- 14709705
TI  - Sorting out the connections between the built environment and health: a
      conceptual framework for navigating pathways and planning healthy cities.
AB  - The overarching goal of this article is to make explicit the multiple pathways
      through which the built environment may potentially affect health and well-being.
      The loss of close collaboration between urban planning and public health
      professionals that characterized the post-World War II era has limited the design
      and implementation of effective interventions and policies that might translate
      into improved health for urban populations. First, we present a conceptual model
      that developed out of previous research called Social Determinants of Health and
      Environmental Health Promotion. Second, we review empirical research from both
      the urban planning and public health literature regarding the health effects of
      housing and housing interventions. And third, we wrestle with key challenges in
      conducting sound scientific research on connections between the built environment
      and health, namely: (1) the necessity of dealing with the possible health
      consequences of myriad public and private sector activities; (2) the lack of
      valid and reliable indicators of the built environment to monitor the health
      effects of urban planning and policy decisions, especially with regard to land
      use mix; and (3) the growth of the "megalopolis" or "super urban region" that
      requires analysis of health effects across state lines and in circumscribed areas
      within multiple states. We contend that to plan for healthy cities, we need to
      reinvigorate the historic link between urban planning and public health, and
      thereby conduct informed science to better guide effective public policy.

PMID- 14709707
TI  - How suburban sprawl shapes human well-being.

PMID- 14709706
TI  - Residential environments and cardiovascular risk.
AB  - The article begins with a discussion of the rationale for studying the
      relationship between residential environments and cardiovascular health. Existing
      empirical research relating residential environments to cardiovascular outcomes
      and risk factors is summarized. The research areas discussed include neighborhood
      socioeconomic characteristics and cardiovascular disease, the effects of
      residential environments on physical activity, and the effects of residential
      environments on diet. Other mechanisms through which residential environments may
      affect cardiovascular health are also briefly noted. Key challenges in
      investigating the relationship between residential environments and health are
      discussed. These challenges include characterizing environments (including
      definition and geographic scale as well as conceptualization and measurement of
      relevant features), the limitations of observational studies, and the need to
      evaluate the health impact of interventions or "naturally" occurring changes in
      local environments. The need for interdisciplinary work is emphasized.

PMID- 14709708
TI  - Integrating behavioral and social science into a public health agency: a case
      study of New York City.
AB  - In the last century, both the health and life expectancy of Americans improved
      dramatically. These gains were primarily the result of advances in public health.
      But the approaches used may not be adequate to achieve the next level of
      improvements in health. Because health exists in the context of social,
      environmental, community, religious, political, and other spheres, ecological
      approaches that incorporate behavioral and social science theory and
      methodologies may provide the best avenue for advancing health in the 21st
      century. In 1999, the New York City Department of Health (NYCDOH) undertook the
      task of integrating behavioral and social science into its public health
      practice. The experience serves as a case study on the integration process at a
      public health agency.

PMID- 14709709
TI  - Use of social and behavioral sciences by public health departments in major
      cities.
AB  - Individual behavior and social contexts are critical determinants of health. We
      surveyed commissioners or their designees in 22 departments of health serving US
      cities of at least 500,000 people to examine their use of scientific approaches
      to influence individual behavior and social contexts. Each department used
      behavioral or social science in its work, but only four departments were judged
      to have integrated these approaches throughout their operations, using both
      centralized and decentralized structures. Degree of integration was unrelated to
      collaboration with universities or communities but was related to use of explicit
      theories. Behavioral and social sciences were employed most frequently in the
      areas of HIV/AIDS and maternal and child health and in the service of changing
      individual behavior rather than larger contexts, although across departments many
      health problems and approaches were involved. Commissioners generally found the
      approaches valuable, but articulated barriers to more widespread adoption.

PMID- 14709710
TI  - The role of social and behavioral science in public health practice: a study of
      the New York City Department of Health.
AB  - Studies over the last decade have demonstrated the effectiveness of public health
      interventions based on social and behavioral science theory for many health
      problems. Little is known about the extent to which health departments are
      currently utilizing these theories. This study assesses the application of social
      and behavioral science to programs in the New York City Department of Health
      (NYCDOH). Structured open-ended interviews were conducted with executive and
      program management staff of the health department. Respondents were asked about
      the application of social and behavioral sciences within their programs, and
      about the benefits and barriers to increasing the use of such approaches. Themes
      related to the aims of the study were identified, a detailed coding manual
      developed, narrative data were coded independently by two investigators
      (kappa.85), and data analyzed. Interviews were conducted with 61 eligible
      individuals (response rate 88%). The most common applications of social and
      behavioral science were individual-level behavior change to prevent HIV
      transmission and community-level interventions utilizing community organizing
      models and/or media interventions for health promotion and disease prevention.
      There are generally positive attitudes about the benefits of utilizing these
      sciences; however, there are also reservations about expanded use because of
      resource constraints. While NYCDOH has successfully applied social and behavioral
      sciences in some areas of practice, many areas use them minimally or not at all.
      Increasing use will require additional resources. Partnerships with academic
      institutions can bring additional social and behavioral science resources to
      health departments and benefit researchers understanding of the health department
      environment.

PMID- 14709711
TI  - The primary care delivery system in New York's low-income communities: private
      physicians and institutional providers in nine neighborhoods.
AB  - Despite a recent policy emphasis on managed care as the preferred method of
      financing and delivering care to Medicaid beneficiaries and other indigent
      populations, there is little information on the availability or the
      characteristics of primary care providers in low-income neighborhoods. Data from
      two independent surveys of primary care were analyzed. A 1998 street canvass of
      each of nine neighborhoods identified 367 primary care offices and 567 private
      practice primary care physicians. Survey data on primary care were collected from
      a total of 280 ambulatory care sites across the city in 1997 and 1999.
      Information on services, hours, and other data on primary care offered at sites
      in these nine neighborhoods was compiled to develop a profile of the primary care
      delivery system. There are relatively few private practice physicians providing
      primary care in these neighborhoods. While there are considerably more primary
      care physicians at the ambulatory care sites, there is a wide variation in supply
      across neighborhoods, driven largely by the presence of sizeable safety-net
      facilities in several of the neighborhoods. Several indicators of access to
      primary care across these neighborhoods show similar neighborhood variations.
      Without primary care availability, managed care's promise of greater access to
      quality care for low-income populations may fall short.

PMID- 14709712
TI  - Income inequality and infant mortality in New York City.
AB  - A series of studies have demonstrated that people who live in regions where there
      are disparities in income have poorer average health status than people who live
      in more economically homogeneous regions. To test whether such disparities might
      explain health variations within urban areas, we examined the possible
      association between income inequality and infant mortality for zip code regions
      within New York City using data from the 1990 census and the New York City
      Department of Health. Both infant mortality and income inequality (percentage of
      income received by the poorest 50% of households) varied widely across these
      regions (range in infant mortality: 0.6-29.6/1,000 live births; range in income
      inequality: 12.7-27.3). An increase of one standard deviation in income
      inequality was associated with an increase of 0.80 deaths/1,000 live births (P
      <.001), controlling for other socioeconomic factors. This finding has important
      implications for public health practice and social epidemiological research in
      large urban areas, which face significant disparities both in health and in
      social and economic conditions.

PMID- 14709713
TI  - Knowledge of, attitudes toward, and stage of change for female and male condoms
      among Denver inner-city women.
AB  - Despite availability for a decade and documented acceptability among some groups
      of women for the method, female condom use is still rare. We surveyed 198 young
      women (15-25 years old) living in the inner city of Denver about their knowledge
      of, attitudes toward, and practices regarding female and male condoms. Most (75%)
      women had ever considered using male condoms; 32% had ever considered using
      female condoms; and use of either was sporadic. We examined predictors for being
      in either precontemplation or a later stage along the change continuum at both
      the bivariate and multivariate levels. Our findings suggest that African
      Americans and younger women are more likely to contemplate using female condoms.
      Both lack of knowledge and positive attitudes toward female condoms in this
      sample suggest that programs designed to raise awareness and knowledge of female
      condoms while improving their image are needed.

PMID- 14709714
TI  - Alcohol use and incarceration adversely affect HIV-1 RNA suppression among
      injection drug users starting antiretroviral therapy.
AB  - We conducted this study among HIV-infected injection drug users to determine the
      effect of self-reported alcohol use and prior incarceration at the time of
      initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We
      examined the demographics, recent incarceration history, and drug and alcohol use
      history from the Vancouver Injection Drug User Study (VIDUS) questionnaire
      closest to the date of initiating antiretroviral therapy. We linked these data to
      the HIV/AIDS Drug Treatment Program. There were 234 VIDUS participants who
      accessed antiretroviral therapy through the Drug Treatment Program from August 1,
      1996, to July 31, 2001. In terms of illicit drug use, 196 (84%) reported
      injecting heroin and cocaine at the time of initiating antiretroviral therapy.
      Multiple logistic regression revealed that in the 6 months prior to initiating
      antiretroviral therapy, alcohol use (adjusted odds ratio [AOR] 0.32; 95% CI 0.13
      0.81) and incarceration (AOR 0.22; 95% CI 0.09-0.58) were independently
      associated with lower odds of HIV-1 RNA suppression. Factors positively
      associated with HIV-1 RNA suppression included: adherence (AOR 1.27; 95% CI 1.06
      1.51); lower baseline HIV-1 RNA (AOR 1.30; 95% CI 1.01-1.66); highly active
      antiretroviral therapy (AOR 4.10; 95% CI 1.56-10.6); months on therapy (AOR 1.1;
      95% CI 1.06-1.14). Among HIV-infected injection drug users who were on
      antiretroviral therapy, any alcohol use and incarceration in the 6 months prior
      to initiating antiretroviral therapy were negatively associated with achieving
      HIV-1 RNA suppression. In addition to addiction treatment for active heroin and
      cocaine use, the identification and treatment of alcohol problems should be
      supported in this setting. As well, increased outreach to HIV-infected drug users
      recently released from prison to ensure continuity of care needs to be further
      developed.

PMID- 14709715
TI  - Mortality rates and causes of death in a cohort of HIV-infected and uninfected
      women, 1993-1999.
AB  - HIV/AIDS-associated and non-HIV/AIDS-associated death rates and causes of death
      between 1993 and 1999 were examined in 885 HIV-infected women and 425 uninfected
      women of the HIV Epidemiology Research Study cohort. Causes of death were
      determined by review of death certificates and the National Death Index. Adjusted
      hazard ratios were calculated for mortality risk factors. In the 885 HIV-infected
      women and 425 uninfected women, 234 deaths and 8 deaths, respectively, occurred
      by December 31, 1999. All-cause death rates in the HIV-infected women were
      unchanged between the pre-HAART (1993-1996) and HAART eras (1997-1999)-5.1 versus
      5.4 deaths per 100 person-years (py). AIDS as a cause of death decreased from 58%
      of all deaths in 1996 to 19% in 1999, while HAART use increased to 42% by the end
      of 1999. In spite of the modest proportion ever using HAART, HIV-related
      mortality rates did decline, particularly in women with CD4+ cell counts less
      than 200/mm(3). Drug-related factors were prominent: for the 129 non-AIDS
      defining deaths, hepatitis C positivity (relative hazard [RH] 2.6, P <.001) and
      injection drug use (RH 1.7, P = 0.02) were strong predictors of mortality, but
      were not significant in the Cox model for 105 AIDS-defining deaths (RH 0.9, P
      >.30 and RH 0.7, P >.30, respectively. The regression analysis findings, along
      with the high percentage of non-AIDS deaths attributable to illicit drug use,
      suggest that high levels of drug use in this population offset improvements in
      mortality from declining numbers of deaths due to AIDS.

PMID- 14709716
TI  - Murine tenascin-W: a novel mammalian tenascin expressed in kidney and at sites of
      bone and smooth muscle development.
AB  - We cloned and characterized a novel member of the tenascin family of
      extracellular matrix proteins--the murine orthologue of zebrafish tenascin-W.
      Full-length recombinant tenascin-W was expressed and purified from mammalian cell
      cultures. Rotary shadowing followed by electron microscopy showed that tenascin-W
      forms hexabrachions. We studied its expression during development and in the
      adult by immunohistochemistry, in situ hybridization and immunoblotting. Tenascin
      W is expressed during palate formation, osteogenesis and smooth muscle
      development. In the adult, tenascin-W is found in the kidney, cardiac semilunar
      valves, corneal limbus and periosteum. Tenascin-W and tenascin-C expression
      overlap in many of these areas. Bone-morphogenic-protein-2 treated C2C12 cells
      secrete tenascin-W and are able to adhere to and to extend actin-rich processes
      on a tenascin-W substratum. In vitro, cells bind to tenascin-W in an RGD
      dependent manner. This adhesion is increased by transfection of alpha8 integrin,
      which localizes with tenascin-W in the periosteum and kidney.

PMID- 14709717
TI  - The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell
      substratum interactions and a reduction in cell proliferation.
AB  - The receptor protein tyrosine phosphatase density-enhanced phosphatase-1 (DEP-1)
      has been implicated in aberrant cancer cell growth and immune cell function,
      however, its function within cells has yet to be properly elucidated. To
      investigate the cellular function of DEP-1, stable cell lines inducibly
      expressing DEP-1 were generated. Induction of DEP-1 expression was found to
      decrease PDGF-stimulated tyrosine phosphorylation of a number of cellular
      proteins including the PDGF receptor, and to inhibit growth factor-stimulated
      phosphorylation of components of the MAPK pathway, indicating that DEP-1
      antagonised PDGF receptor signalling. This was supported by data showing that DEP
      1 expression resulted in a reduction in cell proliferation. DEP-1-expressing
      cells had fewer actin-containing microfilament bundles, reduced vinculin and
      paxillin-containing adhesion plaques, and were defective in interactions with
      fibronectin. Defective cell-substratum adhesion correlated with lack of
      activation of FAK in DEP-1-expressing cells. Time-lapse interference reflection
      microscopy of live cells revealed that although small focal contacts at the
      leading edge were generated in DEP-1-expressing cells, they failed to mature into
      stable focal adhesions, as found in control cells. Further motility analysis
      revealed that DEP-1-expressing cells retained limited random motility, but showed
      no chemotaxis towards a gradient of PDGF. In addition, cell-cell contacts were
      disrupted, with a change in the localisation of cadherin from discrete areas of
      cell-cell contact to large areas of membrane interaction, and there was a
      parallel redistribution of beta-catenin. These results demonstrate that DEP-1 is
      a negative regulator of cell proliferation, cell-substratum contacts, motility
      and chemotaxis in fibroblasts.

PMID- 14709718
TI  - Swm1p subunit of the APC/cyclosome is required for activation of the daughter
      specific gene expression program mediated by Ace2p during growth at high
      temperature in Saccharomyces cerevisiae.
AB  - SWM1 was originally identified for its role in the late steps of the sporulation
      process, being required for spore wall assembly. This protein, recently
      identified as one of the core subunits of the anaphase-promoting complex (APC) is
      also required to complete cell separation in vegetative cells during growth at
      high temperature. Mutants lacking SWM1 show a thermosensitive growth defect that
      is suppressed by osmotic support in the culture medium. At the restrictive
      temperature, swm1 mutants are unable to complete separation, forming chains of
      cells that remain associated and, with prolonged incubation times, the stability
      of the cell wall is compromised, resulting in cell lysis. This separation defect
      is due to a reduction in expression of CTS1 (the gene encoding chitinase) and a
      group of genes involved in cell separation (such as ENG1,SCW11, DSE1 and DSE2).
      Interestingly, these genes are specifically regulated by the transcription factor
      Ace2p, suggesting that Swm1p is required for normal expression of Ace2p-dependent
      genes during growth at high temperatures. Although no defect in Ace2p
      localization can be observed at 28 degrees C, this transcription factor is unable
      to enter the nucleus of the daughter cell during growth at 38 degrees C. Under
      these growth conditions, swm1 cells undergo a delay in exit from mitosis, as
      determined by analysis of Clb2p degradation and Cdc28p-Clb2p kinase assays, and
      this could be the reason for the cytoplasmic localization of Ace2p.

PMID- 14709719
TI  - Trafficking of beta2-adrenergic receptors: insulin and beta-agonists regulate
      internalization by distinct cytoskeletal pathways.
AB  - Insulin and beta-adrenergic agonists stimulate a rapid phosphorylation and
      sequestration of the beta2-adrenergic receptors (beta2ARs). Although the
      expectation was that a common pathway would be involved in the trafficking of the
      beta2AR in response to either hormone, studies reported herein show the existence
      of unique cytoskeletal requirements for internalization/recycling of G-protein
      coupled receptors, such as the beta2AR. Treatment of human epidermoid carcinoma
      A431 cells with nocodazole, which binds tubulin monomer in vivo and catalyzes the
      depolymerization of microtubules, effectively blocks beta-adrenergic agonist
      induced, but not insulin-induced, sequestration of beta2ARs. Treatment with
      latrunculin-A, an agent that sequesters actin monomer and leads to loss of actin
      filaments, had no effect on the ability of beta-adrenergic agonists to stimulate
      internalization of beta2ARs, but blocked the ability of insulin to stimulate
      counterregulation of beta2ARs via internalization. Although nocodazole had no
      effect on insulin-stimulated sequestration of beta2ARs, the recycling of the
      internalized receptors to the cell membrane was sensitive to depolymerization of
      microtubules by this agent. Latrunculin-A, by contrast, blocks the recycling of
      beta2ARs internalized in response to beta-agonist, while attenuating recycling of
      receptors internalized in response to insulin stimulation. These data show the
      existence of unique cytoskeletal requirements for G-protein-coupled-receptor
      trafficking in response to agonist compared with a counterregulatory hormone, and
      for sequestration versus recycling of the receptors to the cell membrane.

PMID- 14709720
TI  - A role for the spectrin superfamily member Syne-1 and kinesin II in cytokinesis.
AB  - Expression of a dominant negative fragment of the spectrin family member Syne-1
      causes an accumulation of binucleate cells, suggesting a role for this protein in
      cytokinesis. An association of this fragment with the C-terminal tail domain of
      the kinesin II subunit KIF3B was identified by yeast two-hybrid and co
      precipitation assays, suggesting that the role of Syne-1 in cytokinesis involves
      an interaction with kinesin II. In support of this we found that (1) expression
      of KIF3B tail domain also gives rise to multinucleate cells, (2) both Syne-1 and
      KIF3B localize to the central spindle and midbody during cytokinesis in a
      detergent resistant and ATP sensitive manner and (3) Syne-1 localization is
      blocked by expression of KIF3B tail. Also, membrane vesicles containing syntaxin
      associate with the spindle midbody with identical properties. We conclude that
      Syne-1 and KIF3B function together in cytokinesis by facilitating the
      accumulation of membrane vesicles at the spindle midbody.

PMID- 14709721
TI  - Mechanism of recruiting Sec6/8 (exocyst) complex to the apical junctional complex
      during polarization of epithelial cells.
AB  - Sec6/8 (exocyst) complex regulates vesicle delivery and polarized membrane growth
      in a variety of cells, but mechanisms regulating Sec6/8 localization are unknown.
      In epithelial cells, Sec6/8 complex is recruited to cell-cell contacts with a
      mixture of junctional proteins, but then sorts out to the apex of the lateral
      membrane with components of tight junction and nectin complexes. Sec6/8 complex
      fractionates in a high molecular mass complex with tight junction proteins and a
      portion of E-cadherin, and co-immunoprecipitates with cell surface-labeled E
      cadherin and nectin-2alpha. Recruitment of Sec6/8 complex to cell-cell contacts
      can be achieved in fibroblasts when E-cadherin and nectin-2alpha are co
      expressed. These results support a model in which localized recruitment of Sec6/8
      complex to the plasma membrane by specific cell-cell adhesion complexes defines a
      site for vesicle delivery and polarized membrane growth during development of
      epithelial cell polarity.

PMID- 14709722
TI  - Gene switching in Amoeba proteus caused by endosymbiotic bacteria.
AB  - The expression of genes for S-adenosylmethionine synthetase (SAMS), which
      catalyzes the synthesis of S-adenosylmethionine (AdoMet), a major methyl donor in
      cells, was studied in symbiont-free (D) and symbiont-bearing (xD) amoeba strains
      to determine the effect of bacterial endosymbionts. The symbionts suppressed the
      expression of the gene in host xD amoebae, but amoebae still exhibited about half
      the enzyme activity found in symbiont-free D amoebae. The study was aimed at
      elucidating mechanisms of the suppression of the amoeba's gene and determining
      the alternative source for the gene product. Unexpectedly, we found a second sams
      (sams2) gene in amoebae, which encoded 390 amino acids. Results of experiments
      measuring SAMS activities and amounts of AdoMet in D and xD amoebae showed that
      the half SAMS activity found in xD amoebae came from the amoeba's SAMS2 and not
      from their endosymbionts. The expression of amoeba sams genes was switched from
      sams1 to sams2 as a result of infection with X-bacteria, raising the possibility
      that the switch in the expression of sams genes by bacteria plays a role in the
      development of symbiosis and the host-pathogen interactions. This is the first
      report showing such a switch in the expression of host sams genes by infecting
      bacteria.

PMID- 14709723
TI  - Chaperone-mediated folding and assembly of myosin in striated muscle.
AB  - De novo folding and assembly of striated muscle myosin was analyzed by expressing
      a GFP-tagged embryonic myosin heavy chain (GFP-myosin) in post-mitotic C2C12
      myocytes using replication defective adenoviruses. In the early stages of muscle
      differentiation, the GFP-myosin accumulates in bright globular foci and short
      filamentous structures that are later replaced by brightly fluorescent
      myofibrils. Time-lapse microscopy shows that the intermediates are dynamic and
      are present in elongating and fusing myocytes and in multinucleated myotubes.
      Immunostaining reveals the co-localization of the molecular chaperones Hsc70 and
      Hsp90 with the GFP-myosin in the intermediates, but not in the mature myofibrils.
      Uninfected cells have similar intermediates suggesting a common pathway for
      myosin maturation. Two conformation-sensitive antibodies that bind the unfolded
      motor domain and the coiled-coil conformation of the rod demonstrate that in the
      intermediates, the myosin rod is folded but the motor domain is not folded.
      Electron microscopy reveals that the intermediates contain loose filament bundles
      surrounded by a protein rich matrix. Geldanamycin, a specific inhibitor of Hsp90,
      reversibly blocks myofibril assembly and triggers accumulation of myosin folding
      intermediates. We conclude that multimeric complexes of nascent myosin filaments
      associated with Hsc70 and Hsp90 are intermediates in the folding and assembly
      pathway of muscle myosin.

PMID- 14709724
TI  - A domain of Rad9 specifically required for activation of Chk1 in budding yeast.
AB  - The Rad9 protein is a key adaptor protein in Saccharomyces cerevisiae DNA damage
      checkpoint pathways. Its adaptor function is to link the activity of the Mec1
      kinase to the activation of two parallel signalling pathways dependent on the
      Rad53 and Chk1 kinases. The mechanisms by which Rad9 interacts with, and
      activates, Rad53 are well understood. However, little was known about how Rad9
      facilitates the activation of Chk1. We show here that the N-terminus of Rad9 is
      specifically important for phosphorylation and activation of the Chk1 kinase but
      not for the phosphorylation and activation of the Rad53 kinase. The Chk1
      activation domain (CAD) of Rad9 is specifically important for signalling cell
      cycle arrest after cdc13-1- and yku70Delta-induced telomere damage but not for
      tolerating ultraviolet-induced damage or inhibiting nuclease activity at
      telomeres. This work extends data showing that separable domains within the Rad9
      adaptor protein allow it to activate two distinct kinase signalling pathways
      independently of each other.

PMID- 14709725
TI  - One less thing to worry about: the shrinking spectrum of tumors in BRCA founder
      mutation carriers.

PMID- 14709726
TI  - What now for aspirin and cancer prevention?

PMID- 14709727
TI  - Birthday of a breakthrough: fibronectin research proves important, but not as
      originally expected.

PMID- 14709728
TI  - 'Mother of psycho-oncology' discusses field's need for parity and people power:
      Jimmie C. Holland interviewed by Rabiya S. Tuma.

PMID- 14709729
TI  - In different cultures, cancer screening presents challenges.

PMID- 14709730
TI  - Stat bite: Cervical cancer mortality by ethnicity and socioeconomic area, 1995
      1999.

PMID- 14709733
TI  - Checking out the neighborhood: researchers examine environment's effect on tumor
      growth.

PMID- 14709734
TI  - BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer.
AB  - BACKGROUND: Mutations in BRCA1 and/or BRCA2 (BRCA1/2) profoundly increase the
      risks of breast and ovarian cancers, but it is unclear whether mutations in these
      genes increase the risk of colorectal cancer. We investigated BRCA1/2 founder
      mutations and a family history of breast cancer as potential risk factors for
      colorectal cancer. METHODS: In the population-based Molecular Epidemiology of
      Colorectal Cancer study in northern Israel, 1422 case patients with incident
      colorectal cancer, diagnosed between March 31, 1998, and December 31, 2002, and
      1566 control subjects without colorectal cancer were genotyped for the BRCA1
      187delAG, BRCA1 5385insC, and BRCA2 6174delT founder mutations. Genotypes and
      interview data from all case patients and control subjects and from only those of
      Ashkenazi Jewish descent (1002 case patients and 1038 control subjects) were used
      to calculate odds ratios [ORs] from logistic regression. RESULTS: Twenty-four
      (2.4%) case patients and 20 (1.9%) control subjects carried one of the three
      mutations (OR = 1.24, 95% confidence interval [CI] = 0.68 to 2.26). A family
      history of breast cancer in a female relative was not associated with an
      increased risk of colorectal cancer, even after adjustment for the presence of a
      BRCA founder mutation (OR = 1.03, 95% CI = 0.75 to 1.41). CONCLUSIONS: Although
      weak associations cannot be excluded, Ashkenazi BRCA founder mutations do not
      confer a strongly elevated risk of colorectal cancer. Similarly, a family history
      of breast cancer does not appear to be a strong risk factor for colorectal cancer
      in this population.

PMID- 14709735
TI  - A prospective study of aspirin use and the risk of pancreatic cancer in women.
AB  - BACKGROUND: In vitro experiments and limited animal studies suggest that aspirin
      and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis.
      Because few studies have examined the association between aspirin use and
      pancreatic cancer in humans and the results have been inconsistent, we examined
      the relationship between aspirin use and the development of pancreatic cancer in
      the Nurses' Health Study. METHODS: Among 88 378 women without cancer at baseline,
      we documented 161 cases of pancreatic cancer during 18 years of follow-up.
      Aspirin use was first assessed at baseline in 1980 and updated biennially
      thereafter. All statistical tests were two-sided. RESULTS: Participants were
      classified according to history of aspirin use. In a multivariable analysis, the
      risk of pancreatic cancer was not associated with current regular aspirin use
      (defined as two or more standard tablets per week; relative risk [RR] = 1.20, 95%
      confidence interval [CI] = 0.87 to 1.65), compared with use of fewer than two
      tablets per week. Increasing duration of regular aspirin use, compared with non
      use, was associated with a statistically significant increase in risk: Women who
      reported more than 20 years of regular aspirin use had an increased risk of
      pancreatic cancer (RR = 1.58, 95% CI = 1.03 to 2.43; P(trend) =.01). Among women
      who reported aspirin use on at least two of three consecutive biennial
      questionnaires compared with consistent non-users of aspirin, the risk increased
      with dose (one to three tablets per week: RR = 1.11, 95% CI = 0.70 to 1.76; four
      to six tablets per week: RR = 1.29, 95% CI = 0.70 to 2.40; seven to 13 tablets
      per week: RR = 1.41, 95% CI = 0.76 to 2.61; and > or = 14 tablets per week: RR =
      1.86, 95% CI = 1.03 to 3.35) (P(trend) =.02). CONCLUSION: Extended periods of
      regular aspirin use appear to be associated with a statistically significantly
      increased risk of pancreatic cancer among women.

PMID- 14709736
TI  - Active smoking, household passive smoking, and breast cancer: evidence from the
      California Teachers Study.
AB  - BACKGROUND: There is great interest in whether exposure to tobacco smoke, a
      substance containing human carcinogens, may contribute to a woman's risk of
      developing breast cancer. To date, literature addressing this question has been
      mixed, and the question has seldom been examined in large prospective study
      designs. METHODS: In a 1995 baseline survey, 116 544 members of the California
      Teachers Study (CTS) cohort, with no previous breast cancer diagnosis and living
      in the state at initial contact, reported their smoking status. From entry into
      the cohort through 2000, 2005 study participants were newly diagnosed with
      invasive breast cancer. We estimated hazard ratios (HRs) for breast cancer
      associated with several active smoking and household passive smoking variables
      using Cox proportional hazards models. RESULTS: Irrespective of whether we
      included passive smokers in the reference category, the incidence of breast
      cancer among current smokers was higher than that among never smokers (HR = 1.32,
      95% confidence interval [CI] = 1.10 to 1.57 relative to all never smokers; HR =
      1.25, 95% CI = 1.02 to 1.53 relative to only those never smokers who were
      unexposed to household passive smoking). Among active smokers, breast cancer
      risks were statistically significantly increased, compared with all never
      smokers, among women who started smoking at a younger age, who began smoking at
      least 5 years before their first full-term pregnancy, or who had longer duration
      or greater intensity of smoking. Current smoking was associated with increased
      breast cancer risk relative to all nonsmokers in women without a family history
      of breast cancer but not among women with such a family history. Breast cancer
      risks among never smokers reporting household passive smoking exposure were not
      greater than those among never smokers reporting no such exposure. CONCLUSION:
      Our study provides evidence that active smoking may play a role in breast cancer
      etiology and suggests that further research into the connection is warranted,
      especially with respect to genetic susceptibilities.

PMID- 14709737
TI  - Consolidation therapy with autologous bone marrow transplantation in adults with
      acute myeloid leukemia: a meta-analysis.
AB  - BACKGROUND: The optimal consolidation therapy for adults who are in first
      remission of acute myeloid leukemia after induction chemotherapy and who do not
      have a histocompatible donor is poorly established. We conducted a meta-analysis
      to compare the efficacy of autologous bone marrow transplantation with that of
      non-myeloablative chemotherapy alone (or no further treatment). METHODS: Eligible
      studies were identified by searching electronic databases and by examining the
      reference lists of relevant studies and review articles. Eligible studies were
      those that prospectively enrolled adults with acute myeloid leukemia and randomly
      assigned patients who were in first remission and who did not have a matched
      sibling donor to one of the two consolidation therapies. Two reviewers
      independently assessed all studies for relevance and validity. We used a fixed
      effects model to calculate the ratio of probabilities for disease-free and
      overall survival at 48 months or at the nearest recorded assessment point for
      each study and for all studies combined. All statistical tests were two-sided.
      RESULTS: We identified 587 potentially relevant studies, 36 of which were
      retrieved for detailed evaluation. In the six studies eligible for this meta
      analysis, a total of 1044 patients were randomly assigned to receive autologous
      bone marrow transplantation or non-myeloablative chemotherapy (five studies) or
      autologous bone marrow transplantation or no further treatment (one study).
      Compared with patients who received chemotherapy or no further treatment,
      patients who received autologous bone marrow transplantation had a better disease
      free survival (ratio of disease-free survival probabilities = 1.24, 95%
      confidence interval [CI] = 1.06 to 1.44; P =.006) but a similar overall survival
      (ratio of overall survival probabilities = 1.01, 95% CI = 0.89 to 1.15; P =.86).
      CONCLUSION: Our results do not support the routine use of autologous bone marrow
      transplantation in adult acute myeloid leukemia patients in first remission.

PMID- 14709738
TI  - Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular
      endothelial growth factor expression.
AB  - BACKGROUND: Alternative treatment options are needed for advanced neuroblastoma
      patients because their prognosis remains poor after intensive chemotherapy.
      Neuroblastoma cells express platelet-derived growth factor (PDGF), stem cell
      factor (SCF), and vascular endothelial growth factor (VEGF) and their respective
      receptors, PDGFR, c-Kit, and Flk-1. We therefore evaluated the effects of
      imatinib mesylate (imatinib), a selective inhibitor of the tyrosine kinase
      activities of c-Kit and PDGFR, on the growth of neuroblastoma cells in vivo and
      in vitro. METHODS: We tested seven human neuroblastoma cell lines for their
      sensitivity to imatinib. Cell viability was assessed by trypan blue dye
      exclusion. Apoptosis was evaluated by nuclear staining, flow cytometry, and
      western blotting. Protein assays included immunoprecipitation, western blotting,
      enzyme-linked immunosorbent assays, and immunohistochemistry. mRNA expression was
      assessed by northern blotting. We used a xenograft model in SCID mice (10 mice
      per group) to evaluate the effects of imatinib oral therapy (50 or 100 mg/kg
      every 12 hours for 14 days) on neuroblastoma tumor growth. All statistical tests
      were two-sided. RESULTS: All seven neuroblastoma cell lines treated with imatinib
      displayed concentration-dependent decreases in cell viability, which coincided
      with an induction of apoptosis, and with ligand-stimulated phosphorylation of c
      Kit and PDGFR. The imatinib concentrations that caused 50% inhibition of growth
      and 50% inhibition of ligand-induced phosphorylation of these receptors were 9-13
      micro M and 0.1-0.5 microM, respectively. Expression of VEGF, but not
      phosphorylation of Flk-1, its receptor, was reduced in neuroblastoma cells
      treated with imatinib at 10 microM or higher. Mice treated with imatinib at 50
      mg/kg or 100 mg/kg had statistically significantly smaller tumors than control
      mice treated with vehicle (mean tumor volume in mice treated with imatinib at 50
      mg/kg = 1546 mm3, in control mice = 2954 mm3; difference = 1408 mm3, 95%
      confidence interval [CI] = 657 to 2159 mm3; P<.001; mean tumor volume in mice
      treated with imatinib at 100 mg/kg = 463 mm3; difference = 2491 mm3, 95% CI =
      1740 to 3242 mm3; P<.001). CONCLUSIONS: Imatinib inhibited the growth of
      neuroblastoma cells in vitro and in vivo. This inhibition was associated with
      suppression of PDGFR and c-Kit phosphorylation and inhibition of VEGF expression.

PMID- 14709739
TI  - Anticancer chemosensitization and radiosensitization by the novel poly(ADP
      ribose) polymerase-1 inhibitor AG14361.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA
      strand breaks. Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging
      chemotherapy and radiation therapy in vitro. Because classical PARP-1 inhibitors
      have limited clinical utility, we investigated whether AG14361, a novel potent
      PARP-1 inhibitor (inhibition constant <5 nM), enhances the effects of
      chemotherapy and radiation therapy in human cancer cell cultures and xenografts.
      METHODS: The effect of AG14361 on the antitumor activity of the DNA alkylating
      agent temozolomide, topoisomerase I poisons topotecan or irinotecan, or x
      irradiation or gamma-radiation was investigated in human cancer cell lines A549,
      LoVo, and SW620 by proliferation and survival assays and in xenografts in mice by
      tumor volume determination. The specificity of AG14361 for PARP-1 was
      investigated by microarray analysis and by antiproliferation and acute toxicity
      assays in PARP-1-/- and PARP-1+/+ cells and mice. After intraperitoneal
      administration, the concentration of AG14361 was determined in mouse plasma and
      tissues, and its effect on PARP-1 activity was determined in tumor homogenates.
      All statistical tests were two-sided. RESULTS: AG14361 at 0.4 micro M did not
      affect cancer cell gene expression or growth, but it did increase the
      antiproliferative activity of temozolomide (e.g., in LoVo cells by 5.5-fold, 95%
      confidence interval [CI] = 4.9-fold to 5.9-fold; P =.004) and topotecan (e.g., in
      LoVo cells by 1.6-fold, 95% CI = 1.3-fold to 1.9-fold; P =.002) and inhibited
      recovery from potentially lethal gamma-radiation damage in LoVo cells by 73% (95%
      CI = 48% to 98%). In vivo, nontoxic doses of AG14361 increased the delay of LoVo
      xenograft growth induced by irinotecan, x-irradiation, or temozolomide by two- to
      threefold. The combination of AG14361 and temozolomide caused complete regression
      of SW620 xenograft tumors. AG14361 was retained in xenografts in which PARP-1
      activity was inhibited by more than 75% for at least 4 hours. CONCLUSION: AG14361
      is, to our knowledge, the first high-potency PARP-1 inhibitor with the
      specificity and in vivo activity to enhance chemotherapy and radiation therapy of
      human cancer.

PMID- 14709740
TI  - Frequency of BRCA1 and BRCA2 mutations in unselected Ashkenazi Jewish patients
      with colorectal cancer.
AB  - Mutations in BRCA1 and BRCA2 that predispose to breast and ovarian cancer are
      detected in approximately 2.5% of the Ashkenazi Jewish population. To explore
      whether carriers of Ashkenazi founder mutations in BRCA1 or BRCA2 have an
      increased risk for colorectal cancer, we screened 586 unselected Ashkenazi Jewish
      case patients with colorectal cancer for the three common founder mutations in
      BRCA1 and BRCA2. We identified six carriers (1.02%) among these case patients.
      After adjusting for age at diagnosis and sex by use of logistic regression
      analysis, we compared the incidence of carriers in this group of 586 case
      patients with that of 5012 Ashkenazi Jewish control subjects without a known
      history of colorectal cancer. The presence of a founder BRCA mutation was not
      associated with the risk of colorectal cancer (relative risk = 0.50, 95%
      confidence interval = 0.22 to 1.14). We thus recommend that counseling for
      colorectal cancer screening and prevention in individuals with BRCA mutations be
      based on the personal and family history of colorectal cancer or associated
      syndromic malignancies.

PMID- 14709741
TI  - Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast
      cancer.
AB  - Recent studies have indicated that the tamoxifen-related risk of uterine corpus
      cancer may be especially high for some uncommon cell types, although the
      magnitude of risk has not been quantified. We evaluated data from 39 451 breast
      cancer patients diagnosed from 1980 through 2000 who were initially treated with
      tamoxifen and found that the overall risk of subsequent uterine corpus cancer was
      increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95%
      confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population.
      The relative risk was substantially higher for malignant mixed mullerian tumors
      (MMMTs) (O/E = 4.62, O = 34, 95% CI = 3.20 to 6.46) than for endometrial
      adenocarcinomas (O/E = 2.07, O = 306, 95% CI = 1.85 to 2.32), although the excess
      absolute risk was smaller-an additional 1.4 versus 8.4 cancers per 10 000 women
      per year, respectively. Among those who survived for 5 years or longer, there was
      an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial
      adenocarcinomas, with patients developing MMMTs having a worse prognosis. These
      findings indicate that tamoxifen may have delayed effects, such as the increased
      risk of MMMTs, rare but aggressive tumors of unclear pathogenesis.

PMID- 14709743
TI  - Re: Etiology of pancreatic cancer, with a hypothesis concerning the role of N
      nitroso compounds and excess gastric acidity.

PMID- 14709755
TI  - The changing content of Psychosomatics: reflection of the growth of consultation
      liaison psychiatry?
AB  - Psychosomatics is the official journal of the Academy of Psychosomatic Medicine,
      the national organization of consultation-liaison psychiatrists. The articles
      published in Psychosomatics, therefore, represent an important element of the
      scholarship of consultation-liaison psychiatry, and the evolution of this
      literature should reflect the development of its knowledge base in the past 40
      years. This paper analyzes the content of Psychosomatics over this period and
      discusses the scientific, academic, and social (including economic and political)
      factors that have influenced the changes in the content of the journal and, thus,
      the subspecialty.

PMID- 14709756
TI  - Identification of traumatic stress reactions in women at increased risk for
      breast cancer.
AB  - It has been shown that the diagnosis and treatment of cancer may constitute a
      traumatic event that generates in patients and some of their family members
      traumatic reactions that are consistent with the symptom profile of posttraumatic
      stress disorder (PTSD). The present study was conducted to establish the degree
      to which women at increased familial risk for breast cancer showed such traumatic
      reactions and to establish which demographic or psychological variables may
      contribute to the experience of such traumatic reactions in at-risk individuals.
      Seventy-three women from the Revlon UCLA Breast Center High Risk Clinic were
      assessed for traumatic reactions that might be consistent with the DSM-IV
      criteria for PTSD. The results showed that women at increased risk for breast
      cancer exhibited traumatic responses similar to those reported by cancer
      patients. When the authors used a self-report instrument that maps onto DSM-IV
      criteria, 4% of the study subjects reported symptoms consistent with criteria for
      a potential diagnosis of PTSD, and an additional 7% of the subjects reported
      symptoms consistent with potentially subclinical levels of PTSD, according to DSM
      IV criteria.

PMID- 14709757
TI  - Effects of duloxetine on painful physical symptoms associated with depression.
AB  - Painful physical symptoms are common features of major depressive disorder and
      may be the presenting complaints in primary care settings. The effect of the dual
      serotonin (5-HT) and norepinephrine reuptake inhibitor duloxetine on emotional
      and painful physical symptoms in outpatients with major depressive disorder was
      evaluated in three randomized, double-blind, placebo-controlled trials. The
      trials' primary objective was to evaluate the effect of duloxetine on mood, and
      subjects were not enrolled on the basis of presence, type, or severity of pain.
      However, the pain-relieving effects of duloxetine were evaluated by a priori
      defined analyses of results from a visual analogue scale and the Somatic Symptom
      Inventory. Compared with placebo, duloxetine was associated with significant
      reduction in pain severity. The authors concluded that duloxetine reduces the
      painful physical symptoms of depression.

PMID- 14709758
TI  - Plasma levels of citalopram in depressed patients with hepatitis C.
AB  - Hepatitis C affects an estimated 4 million Americans and 100 million people
      worldwide. Rates of depression are higher than that seen in the general
      population. Antidepressant therapy is often initiated at lower doses in patients
      with liver disease because of concerns about impaired metabolism and clearance.
      This study assessed plasma levels of citalopram in 15 subjects with hepatitis C
      and major depression during an 8-week trial. The mean citalopram dose at study
      completion was 26.67 mg/day. Mean plasma levels of citalopram, compared with
      levels previously reported, were lower than expected (at 10 mg/day [N = 1]: 21
      ng/ml [N = 1]; at 20 mg/day [N = 8]: mean = 42.25 ng/ml, SD = 18.38; at 30 mg/day
      [N = 1]: 54 ng/ml; at 40 mg/day [N = 5]: mean = 76.2 ng/ml, SD = 35.86). There
      was a tendency for lower plasma levels to be found in those subjects receiving
      interferon, although a statistically significant difference was not observed.
      Citalopram was well tolerated. The results of this study suggest that patients
      with major depression and hepatitis C, but without evidence of severe liver
      disease, may be able to tolerate usual recommended doses of citalopram, thus
      avoiding the potential for undertreatment of the depression.

PMID- 14709759
TI  - Update on psychotropic medication use in renal disease.
AB  - Renal failure is a common medical condition, and many patients have comorbid
      psychiatric disorders. In this review, which is intended as a resource for
      consultation psychiatrists, the authors discuss pharmacokinetic considerations
      and provide information about the use of individual psychotropic medications in
      patients with renal disease. Most psychotropic medications are fat soluble,
      easily pass the blood-brain barrier, are not dialyzable, are metabolized
      primarily by the liver, and are excreted mainly in bile. Consequently, the
      majority of these drugs can be safely used with the end-stage renal disease
      population.

PMID- 14709760
TI  - Association between apolipoprotein E epsilon4 and neuropsychiatric symptoms
      during interferon alpha treatment for chronic hepatitis C.
AB  - Neuropsychiatric complications are common in patients with chronic hepatitis C
      undergoing treatment with interferon alpha. These side effects include
      alterations of mood, cognition, and neuroendocrine function and are
      unpredictable. In a number of neurological disorders characterized by
      neuropsychiatric symptoms and cognitive dysfunction, inheritance of an
      apolipoprotein E (APOE) epsilon4 allele is associated with adverse
      neuropsychiatric outcomes. The authors present evidence that the APOE genotype
      may influence a patient's neuropsychiatric response to interferon alpha
      treatment. The inheritance of APOE genotypes was examined in 110 patients with
      chronic hepatitis C treated with interferon alpha. A retrospective investigation
      was conducted by assessing the rates of psychiatric referral and neuropsychiatric
      symptoms experienced during treatment along with other complaints indicating
      psychological distress. A highly statistically significant association was seen
      between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients
      with an epsilon4 allele were more likely to be referred to a psychiatrist and had
      more neuropsychiatric symptoms during antiviral treatment than those without an
      epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely
      to experience irritability or anger and anxiety or other mood symptoms. These
      data demonstrate that an individual's APOE genotype may influence the
      neuropsychiatric response to antiviral therapy with interferon alpha. Prospective
      studies evaluating the importance of APOE in susceptibility to interferon alpha
      induced neuropsychiatric complications are needed. Moreover, pathways involving
      APOE should be considered in understanding the pathophysiology of interferon
      alpha-induced neuropsychiatric complications.

PMID- 14709761
TI  - Changes in psychological distress of women with breast cancer in long-term
      remission and their husbands.
AB  - The purpose of this randomized, prospective study was to identify factors
      influencing the psychological distress of breast cancer patients and their
      husbands during remission. Background variables and distress levels of 172
      couples in two locations (Graz, Austria, and Jerusalem, Israel) were assessed by
      using three standardized instruments in two interviews conducted 6-8 months
      apart. In both geographic-cultural groups, women whose partners refused to
      participate in the interview reported significantly less perceived family
      support. The global severity index (measuring total psychological distress)
      reflected minor changes in psychological distress of both patients and their
      husbands over time.

PMID- 14709762
TI  - Nonfearful panic disorder in chest pain patients.
AB  - The prevalence of non-fearful panic disorder (panic attacks without the
      experience of fear) was estimated in 199 patients consecutively referred to
      outpatient cardiac investigation for chest pain. Fifty-nine patients met the
      criteria for panic disorder, and 17 patients fulfilled the criteria for non
      fearful panic disorder. The patients with non-fearful panic disorder had lower
      scores on self-reported panic symptoms and lower frequencies of agoraphobia and
      comorbid axis I disorders than the patients with panic disorder and had a higher
      prevalence of somatic disorders than the patients without panic disorder. The
      patients with non-fearful panic disorder did not differ significantly from the
      patients with panic disorder in health-related quality of life.

PMID- 14709763
TI  - Modafinil monotherapy in poststroke depression.

PMID- 14709764
TI  - Lithium-induced nephrogenic diabetes insipidus in a surgical patient.

PMID- 14709765
TI  - Ecstasy: pharmacodynamic and pharmacokinetic interactions.
AB  - At "raves," young people dance and ingest illicit drugs, the most common of which
      is MDMA (N-methyl-3,4,-methylenedioxymethamphetamine) or "ecstasy." This drug is
      metabolized principally through the cytochrome P450 (CYP450) 2D6 enzyme.
      Pharmacokinetic drug-drug interactions can occur if MDMA is combined with other
      recreational or therapeutic drugs that are 2D6 inhibitors. Ecstasy concentration
      may increase to cause toxicity. Since ecstasy is pro-serotonergic, it may also be
      involved in pharmacodynamic drug-drug interactions when other pro-serotonergic
      drugs are combined with it, leading to a central serotonin syndrome. Some drugs
      are both pro-serotonergic and CYP450 2D6 inhibitors and, if co-administered with
      ecstasy, may cause both pharmacokinetic and pharmacodynamic drug-drug
      interactions.

PMID- 14709766
TI  - Zolpidem-induced delirium with mania in an elderly woman.

PMID- 14709767
TI  - Promethazine-induced psychosis in a 16-year-old girl.

PMID- 14709768
TI  - Hypochondriasis and ECT.

PMID- 14709771
TI  - The role of CSF-1 in normal physiology of mammary gland and breast cancer: an
      update.
AB  - Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms
      proto-oncogene) were initially implicated as essential for normal monocyte
      development as well as for trophoblastic implantation. However, studies have
      demonstrated that CSF-1 and CSF-1R have additional roles in mammary gland
      development during pregnancy and lactation. This apparent role for CSF-1/CSF-1R
      in normal mammary gland development is very intriguing because this
      receptor/ligand pair has also been found to be important in the biology of breast
      cancer in which abnormal expression of CSF-1 and its receptor correlates with
      tumor cell invasiveness and adverse clinical prognosis. Recent findings also
      implicate tumor-produced CSF-1 in promotion of bone metastasis in breast cancer,
      and a certain membrane-associated form of CSF-1 appears to induce immunity
      against tumors. This review aims to summarize recent findings on the role of CSF
      1 and its receptor in normal and neoplastic mammary development that may
      elucidate potential relationships of growth factor-induced biological changes in
      the breast during pregnancy and tumor progression.

PMID- 14709772
TI  - Multiple sclerosis: etiological mechanisms and future directions.
AB  - Multiple sclerosis (MS) is a complex human autoimmune-type disease with a
      predominantly unknown etiology. Immunologic destruction of myelin basic protein
      (MBP) throughout the nervous system is the major pathology of multiple sclerosis.
      This review will attempt to update new information about basic mechanisms and
      therapeutic management of the disease. The significance of the structure of MBP
      is discussed with respect to the contribution of such structures to the disease
      process. A number of MBP peptides that serve as the immunodominant antigens in MS
      patients have been identified. These peptides have been studied in animal models
      for their antigenic characteristics and ability to induce disease. Evidence for
      genetic contributions is reviewed with multigenerational twin studies providing
      the best evidence for susceptible haplotypes. The role of microorganisms/viruses
      and environmental agents are discussed as potential etiological factors but are
      now thought to be of minor importance to the primary causal development of the
      disease. Of major consideration are immunological mechanisms that contribute to
      the development of autoimmunity. In particular, antigen expression, cytokine and
      leukocyte interactions, and regulatory T-cells are discussed. Particular
      attention is given to regulatory T-cells (Treg), which help balance/modulate
      other T-cells such as Th1 and Th2 cells, and how such Treg regulate autoimmunity
      is addressed. The importance of the role of Tregs is exemplified by the
      demonstration that administration of oral antigens can induce specific Tregs that
      counteract experimental autoimmune encephalomyelitis in animal models. The
      significance of animal studies to human multiple sclerosis is discussed. A
      potential role for natural antibodies and innate immune mechanisms to help
      provide resistance to disease development is also reviewed. Finally, a variety of
      therapeutic agents that have been and continue to be utilized for multiple
      sclerosis is reviewed. Trials with oral antigens, such as glatirmer acetate
      (copolymer 1) especially in combination with interferon-beta, have shown promise.
      Antibody therapy and bone marrow transplantation are also briefly discussed.

PMID- 14709773
TI  - The asymmetry of existence: do we owe our existence to cold dark matter and the
      weak force?
AB  - A common theme throughout biology is homochirality, including its origin and
      especially implications. Homochirality has also intrigued scientists because of
      the hypothesis that life, as it currently exists, could not have occurred without
      it. In this review, we discuss several hypotheses regarding homochirality and
      their linkage to processes that range from subatomic in scale to processes that
      help define the structure of the universe. More importantly, this exploration
      begins with the knowledge that humans inhabit the universe in which there is an
      excess of normal matter over antimatter. It is a universe characterized by
      homochirality but is nonetheless contained in what is most easily described as a
      3+1 dimensional spacetime wherein most laws of physics are invariant under
      spacetime transformations. This restriction on spacetime poses significant
      constraints on the processes that can be invoked to explain homochirality.
      However, in dealing with such restraints, including the total mass contained in
      the universe, the concepts of cold dark matter and dark energy can be
      incorporated into cosmological models with resultant behaviors and predictions
      very much in accord with the findings of the cosmic background surveys. Indeed,
      the introduction of cold dark matter and dark energy to solve problems relating
      to the mass found in the universe may provide a means for generating the needed
      asymmetry to allow homochirality to arise.

PMID- 14709774
TI  - Ingestion of proanthocyanidins derived from cacao inhibits diabetes-induced
      cataract formation in rats.
AB  - Proanthocyanidins derived from cacao (CLP) have various antipathophysiological
      functions. We have tested whether dietary supplementation with CLP prevents
      cataract formation in rats with diabetes induced by streptozotocin (STZ), using
      histological, histochemical, and biochemical analyses. Starting at 7 days after
      the streptozotocin challenge, the animals were fed either a normal diet or a diet
      containing 0.5% w/w CLP over 10 weeks. There were no significant differences in
      plasma and urine glucose concentrations, plasma fructose amines, and plasma
      thiobarbituric reactive substances (TBARS) between the two dietary groups.
      Antioxidant status as assessed by measuring lipid peroxide production in plasma
      in response to azocompounds was lower in the STZ-rats fed control diet than in
      animals fed CLP. Opacity was first detected in the lenses of the control dietary
      group 5 weeks after STZ injection and cataracts had developed in the majority of
      these animals by 10 weeks. These changes were rarely seen in the STZ/CLP diet
      group. Histological examinations of the eyes of the STZ-treated normal diet group
      revealed focal hyperplasia of the lens epithelium and liquefaction of cortical
      fibers. There were similar but considerably less severe changes in the animals
      fed CLP. Hydroxynonenal (HNE), a marker of oxidative stress, was detected
      immunohistochemically in the lenses of the STZ-treated normal diet group, but not
      of those receiving CLP. Our findings suggest that CLP inhibits diabetes-induced
      cataract formation possibly by virtue of its antioxidative activity.

PMID- 14709775
TI  - Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in
      rats.
AB  - The objective was to investigate the bioavailability and mechanism of calcium
      absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of
      studies was performed in adult Sprague-Dawley male rats. In the first study, each
      group of rats (n = 10/group) was assigned to one of the five test meals labeled
      with (45)Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg
      calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur
      uptake indicated better calcium bioavailability from ASC than AC at both calcium
      loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic
      studies were performed to further investigate the mechanism of superior calcium
      bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses
      of 25 mg Ca as ASC or AC. Each dose contained 20 micro Ci (45)Ca. Two additional
      groups of rats (n = 10/group) received an intravenous injection (iv) of 10 micro
      Ci (45)Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC.
      Sequential blood samples were collected over 48 hrs. Urine and fecal samples were
      collected every 12 hrs for 48 hrs and were analyzed for total calcium and (45)Ca
      content. Total calcium and (45)Ca from serum, urine, and feces were fitted by a
      compartment kinetics model with saturable and nonsaturable absorption pathways by
      WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in
      calcium bioavailability between the two salts was due to differences in saturable
      rather than passive intestinal absorption and not to endogenous secretion or
      calcium deposition rate. The higher bioavailability of calcium ascorbate was due
      to a longer transit time in the small intestine compared with ASC.

PMID- 14709776
TI  - Chylomicron margination, lipolysis, and vitamin a uptake in the lactating rat
      mammary gland: implications for milk retinoid content.
AB  - We have reported previously that the concentration of vitamin A (VA) in the milk
      of lactating rats varies with dietary VA intake, even when plasma retinol
      concentration is unaffected. In the current study, we investigated the role of
      lipolysis in the uptake of chylomicron (CM) VA into mammary tissue of lactating
      rats and estimated the proportion of CM-VA that is associated with the mammary
      gland during CM clearance. Chylomicrons containing [(3)H]VA, mainly as retinyl
      esters, were prepared in donor rats and administered intravenously to lactating
      recipient rats. Chylomicron VA rapidly disappeared from plasma and appeared in
      mammary tissue (maximum within 2-3 mins), followed by a decline. Concomitantly,
      uptake by liver increased continuously, reaching a plateau within 20-30 mins.
      Active lipolysis in mammary tissue was necessary for rapid VA uptake, as
      significantly less CM-VA was recovered in mammary tissue of postlactating rats
      than of lactating rats, after heparin treatment in lactating rats, or after
      injection of preformed CM remnants in lactating rats. [(3)H]Vitamin A uptake by
      mammary tissue increased linearly with CM-VA dose over a 150-fold dose range
      (R(2) = 0.972, P = 0.0001), suggesting a high capacity for uptake and apparent
      first-order assimilation of CM-VA during CM remnant formation in situ. Model
      based compartmental analysis using WinSAAM predicted that approximately 42% of CM
      VA marginated, that is, were temporarily removed, from plasma to the mammary
      glands during lipolysis and that a total of 3.8% of CM-VA was transferred to
      mammary tissue. The model-predicted t(1/2) for CM remnants was 3.04 mins. The
      metabolism of CM-VA in the lactating mammary gland, in proportion to VA
      absorption and CM-VA contents, may explain how milk VA concentration varies even
      when plasma retinol levels are unchanged. The mechanism of CM margination and
      mammary gland uptake described here for VA may be similar for other lipophilic
      substances.

PMID- 14709777
TI  - Dissecting autocrine effects on pulsatile release of gonadotropin-releasing
      hormone in cultured rat hypothalamic tissue.
AB  - The control of reproductive function is manifested centrally through the control
      of hypothalamic release of gonadotropin-releasing hormone (GnRH) in episodic
      events or pulses. For GnRH release to occur in pulses, GnRH neurons must
      coordinate release events periodically to elicit a bolus of GnRH. We used a
      perifusion culture system to examine the release of GnRH from both intact
      hypothalami and enzymatically dispersed hypothalamic cells after challenge with
      GnRH analogs to evaluate the role of anatomical neuronal connections on
      autocrine/paracrine signals by GnRH on GnRH neurons. The potent GnRH agonist des
      Gly(10)-D-Ala(6)-GnRH N-ethylamide, potent GnRH antagonists D-Phe(2)-D-Ala(6)
      GnRH and D-Phe(2,6)-Pro(3)-GnRH or vehicle were infused, whereas GnRH release
      from hypothalamic tissue and cells were measured. PULSAR analysis of GnRH release
      profiles was conducted to evaluate parameters of pulsatile GnRH release. Infusion
      of the GnRH agonist resulted in a decrease in mean GnRH (P < 0.001), pulse nadir
      (P < 0.01), and pulse frequency (P < 0.05) but no effect on pulse amplitude.
      Infusion of GnRH antagonists resulted in an increase in mean GnRH (P < 0.001),
      pulse nadir (P < 0.05), and pulse frequency (P < 0.05) and in GnRH pulse
      amplitude only in dispersed cells (P < 0.05). These results are consistent with
      the hypothesis that GnRH inhibits endogenous GnRH release by an ultrashort-loop
      feedback mechanism and that treatment of hypothalamic tissue or cells with GnRH
      agonist inhibits ultrashort-loop feedback, whereas treatment with antagonists
      disrupts normal feedback to GnRH neurons and elicits an increased GnRH signal.

PMID- 14709778
TI  - Different responses of atrial natriuretic peptide secretion and its receptor
      density to salt intake in rats.
AB  - This study investigated whether high-salt intake influences atrial natriuretic
      peptide (ANP) system, atrial content, and release rate of ANP as well as receptor
      density in the kidney were measured in salt intake rats. Male Sprague-Dawley rats
      received either 0.9% or 2% salt in their drinking water for 10 days. The stretch
      induced ANP secretion from isolated perfused non-beating left atria was
      accentuated, and the production of cGMP by ANP in renal cortical tissue membranes
      were pronounced in rats exposed to 0.9% salt for 10 days but not in rats exposed
      to 2% salt. The levels of ANP receptor density and expression in renal cortex
      were decreased in 2% salt intake rats but not in 0.9% salt intake rats. No
      significant differences in atrial and plasma concentrations of ANP and water
      balance were observed in both salt intakes. Therefore, these results suggest that
      atrial ANP secretion and its binding sites in the kidney may respond differently
      to ingested salt concentrations in rats.

PMID- 14709779
TI  - Inhibition of stimulated ascorbic acid and luteinizing hormone-releasing hormone
      release by nitric oxide synthase or guanyl cyclase inhibitors.
AB  - Ascorbic acid (AA), an antioxidant, is present in high concentrations in the
      hypothalamus. Previously, we have shown that AA inhibited stimulated release of
      luteinizing hormone-releasing hormone (LHRH) from medial basal hypothalami in
      vitro. We have also demonstrated that cell membrane depolarization by high [K(+)]
      media-induced AA release that is blocked by N(G)-mono-methyl-L-arginine, a
      competitive inhibitor of nitric oxide synthase (NOS), indicating that the release
      process is mediated by NO. The release of LHRH is also mediated by NO. We
      hypothesized that AA is a co-transmitter released with classical transmitters
      from synaptic vesicles that acts to reduce chemically the NO formed, thereby
      providing feed-forward inhibitory control over LHRH release. Because NO acts by
      activating guanylyl cyclase (GC) resulting in production of cGMP, in the present
      investigation we studied the effects of an NOS inhibitor LY 83583 and GC
      inhibitor, O.D.Q. to further characterize the role of NO in high [K(+)]-induced
      AA and LHRH release. Medial basal hypothalami were incubated in 0.5 ml of Krebs
      Ringer Bicarbonate buffer or medium containing increased potassium [K(+) = 56 mM]
      for 1 hr or combinations of high [K(+)] + LY 83583 or O.D.Q. for 1 hr. AA and
      LHRH released into the incubation medium were measured by high-pressure liquid
      chromatography and radioimmunoassay, respectively. Cell membrane depolarization
      with high [K(+)] produced a significant increase in both AA and LHRH release. A
      combination of high [K(+)] + LY 83583 or high [K(+)] + O.D.Q. decreased basal AA
      and completely blocked high [K(+)]-induced AA and LHRH release. As in the case of
      high [K(+)], LHRH release induced by the excitatory amino acid N-methyl-D
      aspartic acid (NMDA) was blocked by both the inhibitors. NMDA alone failed to
      alter AA release, but the combined presence of NMDA and the inhibitors totally
      blocked AA release. Because LY 83583 and O.D.Q. were shown to inhibit NOS and
      soluble GC, respectively, the data demonstrate that basal and high [K(+)]-induced
      AA and high [K(+)] and NMDA-stimulated LHRH release were mediated by NO by its
      activation of GC and consequent generation of cGMP.

PMID- 14709780
TI  - Insulin-mediated increase in sympathetic nerve activity is attenuated by C
      peptide in diabetic rats.
AB  - Connecting peptide (C-peptide) is secreted along with insulin in equimolar
      amounts into portal circulation in response to beta cell stimulation. The
      biological function of C-peptide had been mostly limited to establishing the
      secondary and tertiary structure of proinsulin. Recent studies have suggested
      that C-peptide can impact several functions, such as autonomic and sensory nerve
      function, insulin secretion, and microvascular blood flow. In this study we
      examined the effects of C-peptide in the presence or absence of insulin on
      cardiovascular and sympathetic nerve activity in both normal and streptozotocin
      (STZ)-induced diabetic Wistar rats. Animals were made diabetic by a single
      intravenous injection of STZ (50 mg/kg) and maintained for 6 weeks. The diabetic
      animals had higher plasma glucose, lower plasma insulin, and C-peptide, compared
      with the normal animals. To characterize cardiovascular and autonomic nervous
      responses, the animals were anesthetized with urethane/alpha-chloralose and
      instrumented for the recording of mean arterial pressure (MAP), heart rate (HR),
      and lumbar sympathetic nerve activity (LSNA). A bolus administration of C-peptide
      alone did not alter MAP, HR, or LSNA in normal or diabetic animals. The bolus
      administration of insulin alone increased HR and LSNA in normal and diabetic
      animals. However, the administration of insulin plus C-peptide attenuated the
      increase in HR in normals and the increase in LSNA in diabetic rats. We concluded
      that the C-peptides play a role in modulating the insulin-stimulated sympathetic
      nerve response.

PMID- 14709781
TI  - The focal segmental glomerulosclerosis permeability factor: biochemical
      characteristics and biological effects.
AB  - Focal segmental glomerulosclerosis (FSGS) is characterized by steroid resistant
      nephrotic syndrome and progression to end-stage renal disease. Proteinuria in
      certain patients with FSGS may be caused by a circulating factor (FSGS
      permeability factor [FSPF]). The current report documents the biochemical
      characteristics and the biological and molecular effects of 70% ammonium sulfate
      supernatant of plasma from patients with recurrence of FSGS after transplantation
      (FSGS 70% supernatant). FS permeability activity, defined as the capacity of
      plasma from patients with FSGS to increase albumin permeability (P(alb)) of
      isolated glomeruli, was assessed in vitro. Permeability activity was not affected
      by lyophilization. FSPF bound strongly to matrices containing Mono-Q anion
      exchanger or protein A. It eluted from matrix-bound Cibacron blue F3GA over a
      wide range of salt concentrations, indicating a potential binding with other
      proteins, such as albumin. FSPF caused a maximal increase in P(alb) within 2 mins
      of incubation in vitro. Cellular proteins isolated from glomeruli with increased
      P(alb) showed decreased tyrosine phosphorylation of focal adhesion kinase,
      paxillin, and other proteins. Tyrosine phosphatase ]inhibition prevented the
      increase in P(alb). Intravenous administration of as little as 3 mg protein in
      FSGS 70% supernatant increased P(alb), while 9 mg or more were required to
      produce proteinuria. We conclude that FSPF is a low-molecular-weight protein,
      carries an anionic charge, and binds to protein A. Effects of FSPF on the
      glomerular permeability barrier are rapid and dose dependent and involve
      signaling through altered phosphorylation of cellular proteins. Identification of
      these biochemical and biological characteristics may be used to design strategies
      for removing FSPF from circulation and for purification and identification of
      this factor.

PMID- 14709782
TI  - Surfactant releases internal calcium stores in neutrophils by G protein-activated
      pathway.
AB  - Pulmonary surfactant with surfactant-associated proteins (PS+SAP) decreases
      pulmonary inflammation by suppressing neutrophil activation. We have observed
      that PS+SAP inserts channels into artificial membranes, depolarizes neutrophils,
      and depresses calcium influx and function in stimulated neutrophils. We
      hypothesize that PS+SAP suppresses neutrophil activation by depletion of internal
      Ca(++) stores and that PS+SAP induces depletion through release of Ca(++) stores
      and through inhibition of Ca(++) influx. Our model predicts that PS+SAP releases
      Ca(++) stores through insertion of channels, depolarization of neutrophils, and
      activation of a G protein-dependent pathway. If the model of channel insertion
      and membrane depolarization is accurate, then gramicidin-a channel protein with
      properties similar to those of PS+SAP-is expected to mimic these effects. Human
      neutrophils were monitored for [Ca(++)] responses after exposure to one of two
      different PS+SAP preparations, a PS-SAP preparation, gramicidin alone, and
      gramicidin reconstituted with phospholipid (PLG). [Ca(++)] responses were
      reexamined following preexposure to inhibitors of internal Ca(++) release or the
      G protein pathway. We observed that (i) 1% PS+SAP-but not PS-SAP-causes transient
      increase of neutrophil [Ca(++)] within seconds of exposure; (ii) 1% PLG-but not
      gramicidin alone-closely mimics the effect of PS+SAP on Ca(++) response; (iii)
      PS+SAP and PLG equally depolarize neutrophils; (iv) direct inhibition of internal
      Ca(++) stores releases or of G protein activation suppresses Ca(++) responses to
      PS+SAP and PLG; and (v) preexposure to either PS+SAP or PLG inhibits Ca(++)
      influx following fMLP stimulation. We conclude that PS+SAP independently
      depolarizes neutrophils, releases Ca(++) from internal stores by a G protein
      mediated pathway, and alters subsequent neutrophil response to physiologic
      stimulants by depleting internal Ca(++) stores and by inhibiting Ca(++) influx
      during subsequent fMLP activation. The mimicking of these results by PLG supports
      the hypothesis that PS+SAP initiates depolarization via channel insertion into
      neutrophil plasma membrane.

PMID- 14709783
TI  - Effects of genistein or soy milk during late gestation and lactation on adult
      uterine organization in the rat.
AB  - In utero and lactational exposure to estrogenic agents has been shown to
      influence morphological and functional development of reproductive tissues. Thus,
      consumption of dietary phytoestrogens, such as isoflavones, during pregnancy and
      lactation could influence important periods of development, when the fetus and
      neonate are more sensitive to estrogen exposure. In this study, reproductive
      outcomes after developmental exposure to isoflavones were examined in Long-Evans
      rats maternally exposed to isoflavones via a commercial soy beverage or as the
      isolated isoflavone, genistein. Most reproductive endpoints examined at birth,
      weaning, and 2 months of age were not significantly modified in pups of either
      sex after lactational exposure to soy milk (provided to the dams in place of
      drinking water) from birth until weaning. However, soy milk exposure induced a
      significant increase in progesterone receptor (PR) in the uterine glandular
      epithelium of the 2-month-old pups. In pregnant dams treated with genistein (GEN;
      15 mg/kg body weight) by gavage, from Gestational Day 14 through weaning, PR
      expression in the uterine glandular epithelium from 2-month-old GEN-treated
      females (postexposure) was also significantly increased. Diethylstilbesterol
      (DES) also stimulated uterine PR expression only in the glandular but not luminal
      epithelial cells. However, unlike DES, in utero/lactational exposure to GEN did
      not increase expression of the proliferation marker, proliferating cell nuclear
      antigen (PCNA), in the luminal epithelial cells of the 2-month-old rat uteri.
      These experiments demonstrate that developmental exposure to dietary isoflavones,
      at levels comparable to the ranges of human exposure, modify expression of the
      estrogen-regulated PR in the uterus of sexually mature rats weeks after exposure
      ended. Since the PR is essential for regulating key female reproductive
      processes, such as uterine proliferation, implantation, and maintenance of
      pregnancy, its increased expression suggests that soy phytoestrogen exposure
      during reproductive development may have long-term reproductive health
      consequences.

PMID- 14709784
TI  - Urocortin protects coronary endothelial function during ischemia-reperfusion: a
      brief communication.
AB  - Urocortin is a vasodilator peptide related to corticotrophin-releasing factor,
      which may protect myocardium during coronary ischemia-reperfusion. To study
      whether urocortin also protects coronary endothelial function during ischemia
      reperfusion, hearts from Sprague-Dawley rats were perfused at constant flow and
      then exposed to 15 mins ischemia followed by 15 mins reperfusion. In one series
      of experiments, we found that the coronary relaxation to urocortin (10(-11) to
      10(-8) M) was reduced by ischemia-reperfusion (51 +/- 4% vs. 79 +/- 4% of the
      active tone, for the 10(-10) Mdose). In other series of experiments, we observed
      that ischemia-reperfusion reduced the coronary relaxation to a test dose of
      acetylcholine (10(-6) M) (25 +/- 2% vs. 54 +/- 9% of active tone), without
      modifying the relaxation to sodium nitroprusside (10(-6) M). Treatment with a low
      threshold concentration of urocortin (10(-11) M), administered before ischemia
      and during reperfusion, partly improved the coronary relaxation to acetylcholine
      (36 +/- 3% of active tone). These results suggest that ischemia-reperfusion
      impairs the coronary vasodilation to urocortin and produces endothelial
      dysfunction and that this endothelial dysfunction may be improved by urocortin.

PMID- 14709785
TI  - Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque
      model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of substantia
      nigra pars compacta (SNc) neurons. The onset of clinical symptoms only occurs
      after the degeneration has exceeded a certain threshold. In most of the current 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nonhuman primate models,
      nigrostriatal lesions and the onset of PD symptoms are the result of an immediate
      neuronal degeneration in the SNc caused by acute injection of the toxin. In order
      to develop a model that more closely mimics the degeneration pattern of human PD,
      we eventually established a protocol that produces a progressive parkinsonian
      state by treating monkeys repeatedly with MPTP for 15 +/- 2 d. Mean onset of
      parkinsonian symptoms occurred after 13.2 d of treatment. At this time, 56.8 +/-
      6.3% of tyrosine hydroxylase immunoreactive neurons and 75.2 +/- 6.2% of Nissl
      stained cells remained in the SNc. Striatal dopamine transporter (DAT) binding
      and dopamine (DA) content decreased to 19.7 +/- 4.9% and 18.2 +/- 5.6% of
      untreated monkeys. Parallel 123I-PEI single-photon emission computed tomography
      (SPECT) imaging in living animals showed a similar decrease in striatal DAT
      binding. In this article, we examine how this and other chronic MPTP models fit
      with human pathology.

PMID- 14709786
TI  - The mechanism of axon growth: what we have learned from the cell adhesion
      molecule L1.
AB  - Cell adhesion molecules (CAMs) are not just an inert glue that mediates static
      cell-cell and cell-extracellular matrix (ECM) adhesion; instead, their adhesivity
      is dynamically controlled to enable a cell to migrate through complex
      environmental situations. Furthermore, cell migration requires distinct levels of
      CAM adhesivity in various subcellular regions. Recent studies on L1, a CAM in the
      immunoglobulin superfamily, demonstrate that cell adhesion can be spatially
      regulated by the polarized internalization and recycling of CAMs. This article
      examines the molecular mechanism of axon growth, with a particular focus on the
      role of L1 trafficking in the polarized adhesion and migration of neuronal growth
      cones.

PMID- 14709787
TI  - Triggers and mediators of hemorrhagic transformation in cerebral ischemia.
AB  - Intracerebral hemorrhagic transformation is a multifactorial phenomenon in which
      ischemic brain tissue converts into a hemorrhagic lesion with blood-vessel
      leakage, extravasation, and further brain injury. It has been estimated that up
      to 30-40% of all ischemic strokes undergo spontaneous hemorrhagic transformation,
      and this phenomenon may become even more prevalent with the increasing use of
      thrombolytic stroke therapy. An emerging conceptual model suggests that the loss
      of microvascular integrity and disruption of neurovascular homeostasis connects
      the experimental findings of blood-cell extravasation to brain injury after
      hemorrhage. In this short article, we examine mechanisms related to reperfusion
      injury and oxidative stress, leukocyte infiltration, vascular activation, and
      dysregulated extracellular proteolysis as potential triggers of hemorrhagic
      transformation. Perturbations in cell-cell and cell-matrix signaling within the
      hypothesized neurovascular unit may ultimately lead to neuroinflammation and
      apoptotic-like cell death in the parenchyma. Further investigations into the
      molecular mediators of hemorrhagic transformation may reveal new therapeutic
      targets for this clinically complex problem.

PMID- 14709788
TI  - Leptin: a multifaceted hormone in the central nervous system.
AB  - It is well established that the adipocyte-derived hormone leptin is an important
      circulating satiety factor that regulates body weight and food intake via its
      actions on specific hypothalamic nuclei. However, there is growing evidence that
      leptin and its receptors are widely expressed throughout the brain, in regions
      not generally associated with energy homeostasis, such as cortex, cerebellum,
      brainstem, basal ganglia, and hippocampus. In this review the author discusses
      recent advances made in leptin neurobiology, with particular emphasis on the role
      of this endocrine peptide in normal and pathophysiological hippocampal function.

PMID- 14709789
TI  - Wild-type huntingtin plays a role in brain development and neuronal survival.
AB  - While the role of the mutated Huntington's disease (HD) protein in the
      pathogenesis of HD has been the focus of intensive investigation, the normal
      protein has received less attention. Nonetheless, the wild-type HD protein
      appears to be essential for embryogenesis, since deletion of the HD gene in mice
      results in early embryonic lethality. This early lethality is due to a critical
      role the HD protein, called huntingtin (Htt), plays in extraembryonic membrane
      function, presumably in vesicular transport of nutrients. Studies of mutant mice
      expressing low levels of Htt and of chimeric mice generated by blastocyst
      injection of Hdh-/- embryonic stem cells show that wildtype Htt plays an
      important role later in development as well, specifically in forebrain formation.
      Moreover, various lines of study suggest that normal Htt is also critical for
      survival of neurons in the adult forebrain. The observation that Htt plays its
      key developmental and survival roles in those brain areas most affected in HD
      raises the possibility that a subtle loss of function on the part of the mutant
      protein or a sequestering of wild-type Htt by mutant Htt may contribute to HD
      pathogenesis. Regardless of whether this is so, the prosurvival role of Htt
      suggests that HD therapies that block production of both wild-type and mutant Htt
      may themselves be harmful.

PMID- 14709790
TI  - From hindbrain segmentation to breathing after birth: developmental patterning in
      rhombomeres 3 and 4.
AB  - Respiration is a rhythmic motor behavior that appears in the fetus and acquires a
      vital importance at birth. It is generated within central pattern-generating
      neuronal networks of the hindbrain. This region of the brain is of particular
      interest since it is the most understood part with respect to the cellular and
      molecular mechanisms that underlie its development. Hox paralogs and Hox
      regulating genes kreisler/mafB and Krox20 are required for the normal formation
      of rhombomeres in vertebrate embryos. From studies of rhombomeres r3 and r4, the
      authors review mechanisms whereby these developmental genes may govern the early
      embryonic development of para-facial neuronal networks and specify patterns of
      motor activities operating throughout life. A model whereby the regional identity
      of progenitor cells can be abnormally specified in r3 and r4 after a mutation of
      these genes is proposed. Novel neuronal circuits may develop from some of these
      misspecified progenitors while others are eliminated, eventually affecting
      respiration and survival after birth.

PMID- 14709791
TI  - Distinct intracellular Ca2+ response to extracellular adenosine triphosphate in
      pancreatic beta-cells in rats and mice.
AB  - Extracellular adenosine triphosphate (ATP) has distinct effects on insulin
      secretion from pancreatic beta-cells between rats and mice. Using a confocal
      microscope, we compared changes between rats and mice in cytosolic free calcium
      concentration ([Ca2+]c) in pancreatic beta-cells stimulated by extracellular ATP.
      Extracellular ATP (50 microM) induced calcium release from intracellular calcium
      stores by activating P2Y receptors in both rat and mouse beta-cells. The
      intracellular calcium release stimulated by extracellular ATP is significantly
      smaller in amplitude and longer in duration in rat beta-cells than in mouse. In
      response to extracellular ATP, rat beta-cells activate store-operated calcium
      entry following intracellular calcium release. This response is lacking in mouse
      beta-cells. Rat and mouse beta-cells both responded to 9 mM glucose by increasing
      [Ca2+]c. This increase, however, was pronounced only in the rat beta-cells. In 9
      mM glucose, extracellular ATP induced a pronounced calcium release above the
      increased level of [Ca2+]c in rat beta-cells. In mouse beta-cells, however,
      extracellular ATP did not exhibit calcium release on top of the increased level
      of [Ca2+]c in 9 mM glucose. These results demonstrate distinct responses between
      rat and mouse beta-cells to extracellular ATP under the condition of low and high
      glucose. Considering that extracellular ATP inhibits insulin secretion from mouse
      beta-cells but stimulates insulin secretion from rat beta-cells, we suggest that
      store-operated Ca2+ entry may be related to exocytosis in pancreatic rat beta
      cells.

PMID- 14709792
TI  - HSP90 is a key for telomerase activation and malignant transition in
      pheochromocytoma.
AB  - Recent studies on a limited number of pheochromocytomas (PCs) revealed a
      potential role of telomerase in the malignant transition of these tumors.
      Telomerase is a ribonucleoprotein complex that includes the telomerase RNA
      component (hTR), the telomerase-associated protein (TP1), the telomerase
      catalytic subunit (hTERT), and the heat-shock protein 90 (HSP90). The
      interactions between these subunits and the activation machinery of telomerase
      are still unclear. To test whether the expression and regulation of telomerase
      subunits are reflected in the malignant transition of PCs, we determined their
      mRNA and/or protein expression in 28 benign and 9 malignant PCs and compared the
      results with telomerase activity. Reverse transcriptase polymerase chain reaction
      analysis revealed that TP1 was ubiquitously expressed. hTR was found in all
      malignant (100%) and in 13/28 (46%) benign PCs. By contrast, hTERT was clearly
      associated with aggressive biologic behavior. All the malignant (100%) but only
      2/28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs but
      was also expressed at a lower level in benign tumors. High telomerase activity
      was measurable in only hTERT-positive tissues. Our data indicate that hTERT,
      HSP90, and telomerase activity are upregulated in malignant cells of the adrenal
      medulla. Overexpression of HSP90 is an important factor in the activation of
      telomerase via hTERT. The common expression of hTERT and telomerase activity thus
      represents an additional prognostic marker that may identify more aggressive
      tumors.

PMID- 14709793
TI  - Modulatory role of testosterone in plasma leptin turnover in rats.
AB  - We explored whether testosterone influences circulating leptin turnover in rats.
      Sham-operated male and female rats and 21-d gonadectomized rats treated or not
      treated with testosterone propionate were used. Anesthetized rats were implanted
      with an iv catheter, and then blood samples were drawn before and throughout a 60
      min period following systemic leptin administration. Plasma testosterone,
      estradiol, and leptin concentrations were monitored. The results indicated that
      while gonadectomy blunted circulating concentrations of the homologous sex
      steroid, testosterone therapy, in gonadectomized rats, restored plasma
      testosterone concentrations to values found in normal male rats. Pharmacokinetic
      parameters evaluated during the test indicated the following: First, in the
      overall pharmacokinetic analyses, testosterone therapy in gonadectomized rats
      induced a more rapid disappearance of leptin from the circulation. Second,
      orchidectomy significantly enhanced the area under the curve (AUC) of circulating
      leptin, an effect fully reversed by testosterone treatment. Third, testosterone
      treatment in ovariectomized rats significantly decreased the AUC of leptin
      concentrations. Fourth, while gonadectomy alone did not modify circulating leptin
      half-life, conversely, testosterone therapy in gonadectomized rats decreased
      leptin halflife in the circulation. Finally, while orchidectomy reduced leptin
      body clearance, this parameter was increased by androgen therapy in
      gonadectomized rats. Our results strongly support that testosterone could play a
      main role in plasma leptin turnover by increasing leptin clearance rate and
      shortening plasma leptin half-life.

PMID- 14709794
TI  - Characterization of a membrane-associated estrogen receptor in a rat hypothalamic
      cell line (D12).
AB  - The ability of estrogens to produce rapid changes in cellular function has been
      firmly established. The question remains whether these changes are mediated by a
      modified form of the nuclear estrogen receptor (ER) that is associated with the
      plasma membrane (mER) or by a completely novel membrane receptor. Therefore, we
      characterized the biochemical properties of the nuclear and membrane-associated
      ERs expressed endogenously in a rat hypothalamic endothelial cell line (D12).
      Radioligand binding experiments using D12 membrane fractions showed that these
      cells exhibit properties consistent with a binding site specific for estrogens
      (mER). Equilibrium binding assays using [125I]16-alpha-iodo-3,17- beta-estradiol
      revealed saturable binding to mER, an affinity value similar to nuclear ER, with
      differing receptor expression levels. Competition assays revealed that 9 of 12 ER
      ligands tested had comparable affinities for mER and ER. For example, 17-alpha
      estradiol and estrone had similar binding characteristics for both receptors
      while differences were noted for raloxifene, 17beta-estradiol (E2), and
      genistein. Western blot and immunocytochemical analyses using antibodies specific
      for ERalpha confirmed that D12 cells expressed a membrane-associated protein with
      a molecular mass (67 kDa) similar to that of ERalpha that colocalized with
      caveolae-enriched membranes. A rapid increase in intracellar Ca2+ levels in the
      presence of E2 suggests that mER can mediate physiologic changes through calcium
      mobilization. These data support the expression of mER in these brain-derived
      endothelial cells that is similar to, but biochemically distinguishable from,
      nuclear ERalpha.

PMID- 14709795
TI  - Pituitary adenylate cyclase-activating polypeptide does not colocalize with
      vasoactive intestinal polypeptide in the hypothalamic magnocellular nuclei and
      posterior pituitary of cats and rats.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP) immunoreactive cells were demonstrated in the
      hypothalamic magnocellular nuclei in cats and rats. In cats these immunoreactive
      cells were stained without any treatment or intervention; however, in rats we had
      to use the pituitary stalk section to enhance the amount of PACAP and VIP for
      successful immunostaining. In both species the regions occupied by PACAP and VIP
      immunoreactive cells partially overlap each other in the paraventricular and
      supraoptic nuclei. Nevertheless, in either cats or rats PACAP and VIP
      immunoreactivities do not colocalize in the same cells studied by double labeling
      immunohistochemistry (IHC) or by the combination of immunohistochemistry and in
      situ hybridization. As was expected, PACAP and VIP immunoreactive materials were
      stored in different fibers of the posterior pituitary where the distribution of
      PACAP and VIP fibers also showed different patterns: PACAP fibers form a dense
      plexus at the periphery of the posterior lobe, in the vicinity of the
      intermediate lobe; however, the VIP fibers were evenly distributed mainly in the
      center of the posterior lobe. In spite of the high sequence homology of PACAP and
      VIP, the two peptides are synthesized in different subpopulations of hypothalamic
      neurons. This different distribution correlates well with the different role of
      the hypothalamic PACAP and VIP in the biologic clock and in the functions of the
      anterior and posterior pituitary.

PMID- 14709796
TI  - Endocrinologic comparison of activin a secretion during pregnancy and early
      lactation in Japanese monkeys, chimpanzees, and humans.
AB  - Secretion of activin A in Japanese monkeys and chimpanzees during pregnancy and
      early postpartum periods was investigated, and the results were compared with
      those in humans. Plasma activin A increased throughout pregnancy in Japanese
      monkeys, and the level was significantly higher in the third and fourth quarters
      than in the first quarter. After parturition in the Japanese monkey, circulating
      activin A decreased to levels seen during the normal menstrual cycle. In
      chimpanzees, plasma activin A remained low until the third quarter of pregnancy
      and abruptly increased in the fourth quarter. After parturition in chimpanzees,
      however, circulating activin A concentrations still remained as high as levels in
      the fourth quarter until 42 h after parturition, then decreased to nadir levels
      at 1 mo after parturition, suggesting that activin A in chimpanzees may be
      secreted from other organs such as uterus in addition to placenta. Positive
      staining with inhibin/ activin alpha-, betaA-, and betaB-subunit antisera was
      observed in the cytoplasm of the syncytiotrophoblast of term placenta in the
      Japanese monkey, chimpanzee, and human. These results demonstrated that
      circulating activin A gradually increased from early pregnancy in Japanese
      monkey, whereas an abrupt increase occurred at late pregnancy in chimpanzees.
      These results also demonstrated that the syncytiotrophoblast of placenta is the
      source of activin A in Japanese monkeys and chimpanzees as well as humans.

PMID- 14709797
TI  - Low urinary 6-sulfatoxymelatonin levels in patients with severe congestive heart
      failure.
AB  - OBJECTIVE: To assess urinary 6-sulfatoxymelatonin excretion in patients admitted
      to the hospital because of congestive heart failure (CHF). METHODS: Urinary 6
      sulfatoxymelatonin was measured by a specific radioimmunoassay in 33 hospitalized
      patients with CHF and in 146 healthy ambulatory volunteers. Individuals with
      hepatic or renal failure were excluded from the sample. Data were analyzed by the
      Mann-Whitney test and regression analysis. RESULTS: 6-Sulfatoxymelatonin levels
      were significantly lower in CHF patients than controls (median 2.6 vs 6.02
      microg, p < 0.0001). This decrease was observed regardless of beta-adrenergic
      blocker or benzodiazepine medication. A significant decrease in 6
      sulfatoxymelatonin excretion occurred with age. There were no significant
      differences in urinary 6-sulfatoxymelatonin levels between chronic and acute CHF
      patients. CONCLUSIONS: The results suggest that circulating melatonin levels are
      low in patients with CHF. Such a decrease may precede aggravation of heart
      failure.

PMID- 14709798
TI  - Luteinizing hormone acts directly at granulosa cells to stimulate periovulatory
      processes: modulation of luteinizing hormone effects by prostaglandins.
AB  - The midcycle surge of luteinizing hormone (LH) triggers events within the primate
      periovulatory follicle that culminate in follicle rupture and luteinization of
      the follicle wall; these events include the shift from primarily estrogen to
      primarily progesterone production, vascularization of the granulosa cell layer,
      and expression of matrix metalloproteinases and their inhibitors (MMPs and TIMPs)
      thought to be necessary for follicle rupture. However, it is unknown if LH acts
      directly at granulosa cells to regulate these important periovulatory processes.
      The ovulatory LH surge also stimulates the production of prostaglandins (PGs) by
      the follicle just before follicle rupture, suggesting that LH may have both PG
      dependent and PG-independent actions. To address these questions, gonadotropins
      were administered to adult female rhesus monkeys to stimulate the development of
      multiple, large preovulatory follicles. Granulosa cells were aspirated and
      maintained in vitro for up to 48 h in serum-free, chemically defined medium.
      Granulosa cells were cultured with LH alone or in combination with PGs to
      determine if these hormones act directly at granulosa cells to induce the
      production of factors implicated in periovulatory processes. LH treatment
      increased media progesterone (p < 0.05) and vascular endothelial growth factor
      (VEGF; p < 0.05) levels as well as stimulating expression of mRNAs for MMP-1 (p =
      0.05), MMP-9 (p < 0.05), and TIMP-1 (p < 0.05), similar to the effects of an
      ovulatory dose of gonadotropin in vivo. PGE2 alone elevated media progesterone
      levels but decreased LH stimulation of MMP- 1 mRNA (p < 0.05). PGF2alpha reduced
      LH-stimulated TIMP-1 mRNA (p < 0.05) levels. These studies suggest a direct
      action of LH on granulosa cells to stimulate the processes involved in tissue
      remodeling and neovascularization, i.e., MMPs/TIMPs and angiogenic factors, as
      well as steroidogenesis. LH-stimulated PGs may have a regulatory role to modulate
      some effects of the LH surge, such as MMP/TIMP expression.

PMID- 14709799
TI  - Agouti-related protein (AGRP) is conserved and regulated by metabolic state in
      the zebrafish, Danio rerio.
AB  - Agouti-related protein (AGRP) and proopiomelanocortin (POMC) genes encode
      secreted hypothalamic factors regulated by metabolic state in mammals and are
      involved in energy homeostasis. The zebrafish, Danio rerio, is a model system for
      forward genetics in vertebrates: POMC and AGRP in this organism have not been
      well characterized. Toward this end, AGRP and POMC were cloned from zebrafish.
      Zebrafish AGRP cDNA encodes a 127-amino-acid protein 36% and 40% identical to
      human and mouse AGRP, respectively. Zebrafish POMC cDNA encodes a 222-amino-acid
      preprohormone. Sequence identity to the mammalian ortholog is about 50%.
      Zebrafish AGRP and POMC transcripts were detected at 24 h post-fertilization
      (hpf) by RTPCR, and in situ hybridization demonstrated zebrafish AGRP mRNA
      exclusively in hypothalamus and POMC mRNA in hypothalamus and pituitary. Fasting
      did not alter POMC transcript levels, while AGRP transcripts were significantly
      upregulated. The ratio of AGRP/POMC transcripts in adult brain was increased up
      to threefold by fasting. These results demonstrate that the melanocortin system
      is regulated by metabolic state in zebrafish, and this finding thus provides a
      vertebrate system for the genetic analysis of the role of the melanocortin system
      in energy homeostasis.

PMID- 14709800
TI  - Macroprolactinemia: the consequences of a laboratory pitfall.
AB  - The objective of this study was to assess the prevalence of macroprolactin, a
      macromolecule with reduced bioactivity, in hyperprolactinemic patients. Prolactin
      was measured before and after precipitation of macroprolactin by polyethylene
      glycol in 306 patients. Only patients with prolactin values >700 mIU/L (n = 270)
      entered the study. In 23% of the patients, macroprolactinemia was found. In
      women, the occurrence of macroprolactinemia increased with advancing age (< 30
      yr: 16%; 30-45 yr: 28%; > 45 yr: 42%; p < 0.05). A priori clinical signs of
      hyperprolactinemia (morphological abnormalities in pituitary imaging,
      galactorrhea infertility) occurred significantly less frequently in
      macroprolactinemia than in true hyperprolactinemia. In eight females
      macroprolactinemia and true hyperprolactinemia appeared simultaneously. To avoid
      diagnostic and therapeutic pitfalls, the screening for macroprolactinemia of all
      patients with prolactin levels of > 700 mIU/ L is recommended.

PMID- 14709801
TI  - The food contaminants bisphenol A and 4-nonylphenol act as agonists for estrogen
      receptor alpha in MCF7 breast cancer cells.
AB  - Xenoestrogens are chemically distinct industrial products potentially able to
      disrupt the endocrine system by mimicking the action of endogenous steroid
      hormones. Among such compounds, the ubiquitous environmental contaminants
      bisphenol A (BPA) and 4-nonylphenol (NPH) may promote adverse effects in humans
      triggering estrogenic signals in target tissues. Following a research program on
      human exposure to endocrine disruptors, we found contamination of fresh food by
      BPA and NPH. More important, these contaminants were found to display estrogen
      like activity using as a model system the estrogen-dependent MCF7 breast cancer
      cells (MCF7wt); its variant named MCF7SH, which is hormone-independent but still
      ERalpha-positive, and the steroid receptor-negative human cervical carcinoma HeLa
      cells. In transfection experiments BPA and NPH activated in a direct manner the
      endogenous ERalpha in MCF7wt and MCF7SH cells, as the antiestrogen
      hydroxytamoxifen was able to reverse both responses. Moreover, only the hormone
      binding domains of ERalpha and ERbeta expressed by chimeric proteins in HeLa
      cells were sufficient to elicit the transcriptional activity upon BPA and NPH
      treatments. Transfecting the same cell line with ERalpha mutants, both
      contaminants triggered an estrogen-like response. These transactivation
      properties were interestingly supported in MCF7wt cells by the autoregulation of
      ERalpha which was assessed by RT-PCR for the mRNA evaluation and by
      immunoblotting and immunocytochemistry for the determination of protein levels.
      The ability of BPA and NPH to modulate gene expression was further confirmed by
      the upregulation of an estrogen target gene like pS2. As a biological
      counterpart, concentrations of xenoestrogens eliciting transcriptional activity
      were able to stimulate the proliferation of MCF7wt and MCFSH cells. Only NPH at a
      dose likely too high to be of any physiological relevance induced a severe
      cytotoxicity in an ERalpha-independent manner as ascertained in HeLa cells. The
      estrogenic effects of such industrial agents together with an increasing
      widespread human exposure should be taken into account for the potential
      influence also on hormone-dependent breast cancer disease.

PMID- 14709802
TI  - Regulation of cell growth and expression of 7B2, PC2, and PC1/3 by TGFbeta 1 and
      sodium butyrate in a human pituitary cell line (HP75).
AB  - Recent studies have shown that 7B2 and the neuroendocrine- specific proconvertase
      PC2 have important roles in pituitary cell proliferation and hormone secretion.
      Studies from our laboratory have also shown that TGFb1 regulates anterior
      pituitary cell proliferation and hormone secretion. To study the regulation of
      7B2 in human pituitary tumors, we used a cell line derived from a human pituitary
      adenoma (HP75) that has been shown to express 7B2, PC1, PC2, and TGFbeta
      receptors to analyze the effects of TGFbeta1 and the histone deacetylase
      inhibitor (HDACI) sodium butyrate (NaB) treatment on 7B2 mRNA expression along
      with the neuroendocrine-specific proconvertases 1/3 (PC1) and PC2 mRNA and
      protein expression. RNA was quantified by real-time PCR and proteins were
      detected by immunohistochemistry and Western blotting. Treatment of cells with 1
      mM NaB or 1 nM TGF 1 for 4 d decreased cell proliferation with a concomitant
      increase in the cell cycle protein p21. Real-time PCR analysis showed a
      significant increase in 7B2 mRNA after NaB and TGFbeta1 treatment. PC2 mRNA was
      down regulated by NaB while PC1 mRNA was unchanged. TGFbeta1 stimulated PC1, but
      not PC2 mRNA levels. Changes in PC1 and PC2 protein were similar to changes in
      the mRNAs, but the differences were not significant. These results indicated that
      NaB and TGFbeta1 inhibit pituitary cell proliferation and regulate the expression
      of 7B2, PC1, and PC2 in a cell culture model of pituitary tumors. Our results
      also indicate that inhibition of pituitary cell proliferation is associated with
      increased expression of 7B2 mRNA.

PMID- 14709803
TI  - Inducible expression of dominant negative insulin-like growth factor I receptor
      in MCF-7 breast cancer cells.
AB  - The insulin-like growth factor I receptor (IGF-IR) is expressed in many cell
      types and is critical for normal growth and development. In the healthy mammary
      gland, the role of IGF-IR is not fully elucidated. However, IGF-IR, which is
      primarily expressed in the mammary epithelial cells, is known to play an
      obligatory role in cellular transformation, facilitating the progression to
      breast cancer. We have utilized the tetracycline regulatory (tet-on) system to
      generate an in vitro model system to allow us to further investigate IGF-I/IGF-IR
      function in mammary epithelial cells. A plasmid construct containing a mutant IGF
      I receptor (IGF-IR-DN) fused to the tetracycline operator (tetOPh(CMV)-IGF-IR-DN)
      was stably transfected into MCF-7 human breast cancer cells. The conditional
      regulation of the IGF-IR-DN gene expression was studied in four independent
      clonal lines. The translated IGF-IR-DN protein was detected only in the stably
      transfected doxycycline- induced cells, and its expression was up-regulated
      (three- to sixfold) following induction. IGF-I stimulated cell proliferation
      diminished (twofold) in doxycycline- induced cells compared to uninduced cells,
      demonstrating that the transgene construct was functional and ruling out any
      pleiotropic effect that may be attributed to doxycycline. Interestingly,
      autophosphorylation of the IGF-IR and phosphorylation of the downstream
      substrate, insulin receptor substrate-1 (IRS-1), was not inhibited in
      doxycycline/IGF-I treated cells, suggesting the possibility that activation of
      downstream substrates other than the IRS-1 may be critical for optimal cell
      proliferation. This novel in vitro model should allow us to more directly examine
      the role of IGF-I/IGF-IR signaling and function in mammary epithelial cells.

PMID- 14709805
TI  - Evolved regulation of gonadotropin-releasing hormone receptor cell surface
      expression.
AB  - Dominant negative effects of mutant gonadotropin-releasing hormone (GnRH)
      receptors (GnRHR; isolated from patients with idiopathic hypogonadotropic
      hypogonadism) on plasma membrane expression (PME) and function of the wt GnRHR
      were examined. In addition, we assessed the effect of mutants on wt GnRHR with
      receptor modifications that, by themselves, diminished PME. Among such mechanisms
      that restrict PME of GnRHR in primates are: (a) addition of the primate-specific
      K191 and (b) deletion of the carboxyl tail ("Ctail") found in pre-mammalian
      species (fish, birds) of GnRHR. We prepared rat (r) and human (h) GnRHR plasmids
      (88% homologous), each with or without the K191; chimeras were then made with C
      tail or each of four truncated fragments (selected to isolate consensus sites for
      palmitoylation or phosphorylation) of the 51-amino-acid Ser-rich piscine GnRHR C
      tail and then expressed in COS-7 cells. The data suggest that the dominant
      negative effect of the mutants on the hGnRHR requires intrinsic low PME that co
      evolved with the dominant-negative effect. The data further reveal that
      additional modifications must have occurred in primates that are important for
      both the diminution of the PME and the development of the dominant negative
      effect of the mutants.

PMID- 14709804
TI  - Tamoxifen is an estrogen antagonist on gonadotropin secretion and responsiveness
      of the hypothalamic-pituitary- adrenal axis in female monkeys.
AB  - The selective estrogen receptor modulator, tamoxifen, effectively slows the
      progression of estrogen-positive breast cancer and reduces the possibility of
      this cancer developing in women at high risk. Despite the widespread acceptance
      of tamoxifen as a therapeutic agent for this disease, its effects on other
      estrogen-dependent pathways, particularly on neural circuits regulating brain
      function and peripheral hormone secretion, are poorly understood. The present
      study, using previously ovariectomized rhesus monkeys, examined the effects of
      tamoxifen, in both the presence and absence of estradiol replacement, on the
      reproductive and hypo-thalamic-pituitary-adrenal (HPA) axes. In Experiment 1,
      monkeys randomly assigned to three groups (n = 8 each) were treated with placebo
      and either two doses of estradiol, two doses of tamoxifen alone, or two doses of
      tamoxifen plus high-dose estradiol to assess the effects on negative feedback
      suppression of luteinizing hormone (LH). Both doses of tamoxifen effectively
      antagonized the negative feedback efficacy of estradiol on LH secretion. In
      contrast, neither the low- or high-dose tamoxifen alone had any effect on LH
      secretion, as concentrations during tamoxifen treatments were indistinguishable
      from those during placebo. In Experiment 2, females were randomly assigned to one
      of four treatment groups (placebo, n = 6; estradiol, n = 5; tamoxifen only, n =
      5; or tamoxifen plus estradiol, n = 6) to assess the effects on glucocorticoid
      negative feedback and pituitary and adrenal responsiveness to exogenous
      corticotropin- releasing hormone (CRH). Tamoxifen also antagonized the
      facilitating effects of estradiol on basal and CRH-induced ACTH and cortisol
      secretion. However, this antagonism produced basal and CRH-stimulated cortisol
      and ACTH concentrations that were lower than placebo-treated females.
      Interestingly, tamoxifen in the absence of estradiol produced a similar
      diminution in ACTH and cortisol response. These data suggest that, in the
      presence of estradiol, tamoxifen not only antagonized estrogenic facilitation of
      HPA responsivity but also actually attenuated the response compared with the
      placebo-treatment condition. Taken together, these data indicate that tamoxifen
      acts as an estrogen antagonist on the neural circuits controlling the
      neuroendocrine regulation of the hypothalamic-pituitary-ovarian and adrenal axes
      in ovariectomized macaque females.

PMID- 14709806
TI  - Chronic daily ethanol and withdrawal: 5. Diurnal effects on plasma thyroid
      hormone levels.
AB  - We previously demonstrated that chronic daily ethanol consumption and daily
      withdrawal by male rats in a modified ethanol liquid diet paradigm produced (a)
      chronically increased adrenal glucocorticoid activity; (b) decreased plasma
      testosterone; (c) decreased forebrain proopiomelanocortin gene expression; and
      (d) corresponding alterations in plasma leptin levels-all of which are consistent
      with reported changes during alcohol abuse and alcoholism. Each of these systems
      interact with hypothalamo-pituitary-thyroid (HPT) regulation, and links between
      chronic alcohol abuse and thyroid dysfunction have been suggested by both human
      and rat studies. Accordingly, we have begun to investigate potential HPT
      mediation of, or response to, alterations in these systems by investigating
      plasma thyroid hormone levels in the same chronic daily ethanol/ withdrawal
      paradigm. Chronic daily episodes of ethanol consumption and withdrawal by male
      Sprague- Dawley rats decreased plasma levels of free (non-protein- bound)
      triiodothyronine (T3) (p < 0.01) and free thyroxine (T4) (p < 0.05) in the
      morning but not in the afternoon, relative to both ad libitum-fed and pair-fed
      controls (n = 9/treatment). Plasma total T4 levels were likewise suppressed (p <
      0.01) in the morning, whereas total T3 levels were increased (p < 0.05) in the
      afternoon. These changes eliminated normal diurnal patterns (higher in the
      morning) of plasma free T3, free T4, and total T3 concentrations. Three weeks
      after cessation of ethanol consumption, morning plasma levels of free and total
      T3 and T4, as well as plasma thyroid-stimulating hormone (TSH), were all not
      significantly changed by the prior ethanol consumption or pair-feeding. These
      results reveal that plasma thyroid hormone concentrations are suppressed in a
      time of day dependent manner by chronic daily ethanol consumption and daily
      withdrawal in this model of chronic ethanol abuse. During subsequent long-term
      "abstinence," these thyroid hormones returned to control levels. These results
      are consistent with evidence that thyroid function is commonly diminished in
      alcoholism, with variable reports of recovery during abstinence. Further
      investigations with this rat model of daily ethanol consumption and daily
      withdrawal will help resolve interactions and roles of the HPT axis in alcohol
      abuse.

PMID- 14709808
TI  - Stimulus-induced behavior in F1 hybrids of seizure-sensitive and seizure
      resistant gerbils.
AB  - We previously established two strains of Mongolian gerbil: a seizure-sensitive
      strain, established by selective inbreeding for motor seizures elicited by a
      stimulus called the S method and a seizure-resistant strain that does not exhibit
      inducible seizures. The behavior of the seizure-sensitive strain is characterized
      by a progressive increase in responsiveness to weekly application of the S
      method, from repetitive backward ear movements appearing after postnatal day 40,
      to a full-blown seizure, while the seizure-resistant strain is apparently
      unaffected by the stimulation. The difference between these two strains is
      presumably genetic. To determine the genetic factors underlying this difference,
      we first examined developmental changes in the stimulus-induced behavior of the
      F1 hybrids. When the S method was applied, most F1 hybrids had repetitive
      movements of the ears (and head) similar to the seizure-sensitive gerbils, but
      generalized seizures emerged considerably later than in seizure-sensitive
      gerbils. These results suggest that a half dose of the gene products involved
      renders most gerbils susceptible to the stimulus but is insufficient for the
      rapid accumulation of an as yet undefined change needed to spread the abnormal
      electrophysiologic activity to elicit generalized seizures.

PMID- 14709807
TI  - Frequent appearance of autoantibodies against prohormone convertase 1/3 and
      neuroendocrine protein 7B2 in patients with nonfunctioning pituitary
      macroadenoma.
AB  - Among pituitary disorders having mass effect of the pituitary gland,
      nonfunctioning pituitary macroadenoma and lymphocytic hypophysitis are difficult
      to differentiate without histological examination. In order to efficiently
      distinguish lymphocytic hypophysitis and pituitary tumors, we studied the
      presence of autoantibodies against prohormone-processing enzymes, prohormone
      convertase (PC) 1/3, PC2, carboxypeptidase E (CPE), and PC2 regulatory protein,
      7B2, by radioligand assay using recombinant human 35S-labeled protein in patients
      with clinically nonfunctioning pituitary macroadenoma, lymphocytic hypophysitis,
      and other pituitary diseases. The indexes for anti-PC1/3 antibodies (Ab) were
      significantly higher in patients with nonfunctioning pituitary macroadenoma than
      in patients with lymphocytic hypophysitis. Patients positive for either anti
      PC1/3 or anti-7B2 Ab were significantly frequent among patients with
      nonfunctioning pituitary macroadenoma than in other pituitary diseases and
      healthy controls. None of the patients was positive for anti-PC2 Ab or anti-CPE
      Ab. These results suggest that autoantibodies against PC1/3 and 7B2 are novel
      tumor-associated autoantibodies and can be helpful in the diagnosis of clinically
      nonfunctioning pituitary macroadenoma.

PMID- 14709809
TI  - Classical olfactory conditioning in the cockroach Periplaneta americana.
AB  - We established a classical conditioning procedure for the cockroach, Periplaneta
      americana, by which odors were associated with reward or punishment. Cockroaches
      underwent differential conditioning trials in which peppermint odor was
      associated with sucrose solution and vanilla odor was associated with saline
      solution. Odor preference of cockroaches was tested by allowing them to choose
      between peppermint and vanilla sources. Cockroaches that had undergone one set of
      differential conditioning trials exhibited a significantly greater preference for
      peppermint odor than did untrained cockroaches. Memory formed by three sets of
      differential conditioning trials, with an inter-trial interval of 5 min, was
      retained at least 4 days after conditioning. This conditioning procedure was
      effective even for cockroaches that had been harnessed in plastic tubes. This
      study shows, for the first time in hemimetaborous insects, that both freely
      moving and harnessed insects are capable of forming olfactory memory by classical
      conditioning procedure. This procedure may be useful for future
      electrophysiological and pharmacological studies aimed at elucidation of neural
      mechanisms underlying olfactory learning and memory.

PMID- 14709810
TI  - Unique behavior and function of the mitochondrial ribosomal protein S4 (RPS4) in
      early Dictyostelium development.
AB  - Certain proteins encoded by mitochondrial DNA (mt-DNA), including mt-ribosomal
      protein S4 (rps4), appear to play important roles in the initiation of cell
      differentiation. Partial disruption of rps4 in Dictyostelium discoideum Ax-2
      cells by means of homologous recombination greatly impairs the progression of
      differentiation, while the the rps4(OE) cells in which the rps4 mRNA was
      overexpressed in the extra-mitochondrial cytoplasm exhibit enhanced
      differentiation (Inazu et al., 1999). We have prepared a specific anti-RPS4
      antibody and generated transformants (rps4(AS) cells) by antisense-mediated gene
      inactivation of rps4. Surprisingly, in the rps4(AS) cells the progress of
      differentiation was found to be markedly inhibited, suggesting that the antisense
      rps4 RNA synthesized in the extra-mitochondrial cytoplasm might be as effective
      as the partial disruption of rps4 gene. Immunostaining of the rps4(OE) cells with
      the anti-RPS4 antibody demonstrated that the RPS4 protein synthesized in the
      extra-mitochondrial cytoplasm is capable of moving to the nucleus, as predicted
      by PSORTII. Taken together with the results obtained using immunostained Ax-2
      cells, we propose a possible pathway of RPS4 translocation coupled with
      differentiation.

PMID- 14709811
TI  - Occurrence of two types of Hynobius naevius in Northern Kyushu, Japan (Amphibia:
      Urodela).
AB  - A survey to examine genetic variation among Hynobius naevius from four localities
      of Fukuoka Pref., northern Kyushu, Japan, resulted in the detection of two,
      sympatric, genetic types (A and B) that are clearly different in the allelic
      frequencies of four loci (ACOH-A, ACOH-B, ADH-A, and SOD-A) in each locality.
      Morphological investigations between the two genetic types also proved that they
      are clearly discriminated; the type A is about 75 mm in SVL, lacks mottling
      pattern on bluish purple dorsum, and possesses relatively short vomerine teeth
      series, while the type B is about 60 mm in SVL, and has light mottling on reddish
      purple ground color. These results strongly suggest that reproductive isolation
      occurs between these two types, and that they could be regarded as separate
      species. Populations from Toyota-cho, western Honshu, and Yabe-machi, central
      Kyushu, both close to Fukuoka Pref., were very similar to the types A and B,
      respectively. From these results, we consider that two evolutionary lineages that
      first evolved allopatrically in western Honshu and southern Kyushu secondarily
      contacted and became sympatric in the region of northern Kyushu.

PMID- 14709812
TI  - Phylogeography and population structure of the Japanese wild boar Sus scrofa
      leucomystax: mitochondrial DNA variation.
AB  - Phylogeographic characteristics and population structure of Japanese wild boar
      (Sus scrofa leucomystax) were investigated using mitochondrial DNA (mtDNA)
      sequence data. Sixteen Japanese wild boar haplotypes detected from partial
      sequences of the mtDNA control region (574-bp) from 180 Japanese wild boar
      specimens from 10 local populations on Honshu, Shikoku, and Kyushu islands and 41
      haplotypes from other S. scrofa were analyzed using the neighbor-joining method.
      The Japanese wild boars were more closely related to Northeast Asian wild boars
      from Mongolia than to the other Asian continental S. scrofa. The Japanese and
      Northeast Asian wild boars were not significantly distinguished by corrected
      average pairwise difference analysis. The ancestors of Japanese wild boars are
      suggested to have been part of the continental S. scrofa population that spread
      from Southeast to Northeast Asia during the Middle to Late Pleistocene. The
      Japanese wild boar mtDNA haplotype cladogram shows 95% parsimoniously plausible
      branch connections supporting three sympatric clades. Nested clade analysis
      indicates that these three clades are the result of distinct historical events or
      gene flow. The present population of Japanese wild boars may have been formed by
      a few independent migrations of distinct clades from the continent with
      subsequent mixing on the Japanese Islands.

PMID- 14709813
TI  - In vitro susceptibility and a new point mutation associated with tylosin
      resistance in Japanese canine intestinal spirochetes.
AB  - The in vitro susceptibilities of six commonly used antimicrobial agents against
      29 isolates of intestinal spirochetes isolated from dogs in Japan were examined
      by the agar dilution technique. In addition, the genetic basis of tylosin
      resistance in in vitro selected resistant mutants of two reference strains and
      three tylosin-susceptible field isolates obtained by three successive subcultures
      on blood agar containing 1 microg/ml of tylosin was investigated. Carbadox was
      the most active (MIC: < 0.00625) of all the antimicrobial agents. Although all
      the isolates were susceptible to tylosin, some were resistant to erythromycin.
      Tiamulin, lincomycin and dimetridazole were also very active against the
      isolates. All the resistant isolates did not harbor any plasmids. In vitro
      selected tylosin-resistant mutants of previously tylosin-susceptible isolates
      showed a new mutation in which their adenine at the base position equivalent to
      2062 of 23S rDNA of Escherichia coli has been replaced by cytosine. These
      findings may both provide guidance towards the proper choice of antimicrobial
      agents for the treatment of canine intestinal spirochetosis, and add to the
      understanding of the genetic basis of tylosin resistance.

PMID- 14709814
TI  - Serum from dogs Infected with Babesia gibsoni inhibits maturation of
      reticulocytes and erythrocyte 5'-nucleotidase activity in vitro.
AB  - Erythrocyte 5'-nucleotidase is thought to be involved in the maturation of
      erythrocytes. In the present study, in vitro incubation of canine erythrocytes
      demonstrated that significant inhibition of 5'-nucleotidase activity occurred in
      the presence of serum from dogs infected with Babesia gibsoni, when the enzyme
      was assayed with cytidine 5'-monophosphate (5'-CMP) and inosine 5'-monophosphate
      (5'-IMP) as substrates. The multiplication of B. gibsoni in in vitro culture also
      resulted in a significant decrease in the enzyme activity of erythrocytes in the
      culture. Furthermore, the infected serum and 5'-CMP retarded the maturation of
      canine reticulocytes in vitro. These results suggested that nucleotides such as
      5'-CMP and 5'-IMP might accumulate in young erythrocytes and/or serum in dogs
      infected with B. gibsoni as a result of decreased activity of erythrocyte 5'
      nucleotidase, resulting in the delayed maturation of reticulocytes.

PMID- 14709815
TI  - Re-serviced females on commercial swine breeding farms.
AB  - The objectives of this study were to observe subsequent reproductive performance
      of re-serviced females by the number of services within a parity, to measure mean
      days to re-service and culling intervals, to determine lifetime performance in re
      serviced gilts, and to investigate re-serviced females across parities on
      commercial farms. Reproduction records on 539 U.S.A. farms were used to observe
      re-serviced females by the number of service groups at the herd level. Farrowing
      rate decreases by approximately 10%, and re-service occurrence increases by
      approximately 5% for each increase in the number of services increase within a
      parity group (P<0.05). Only in parity 0 to 2 groups, average pigs born alive at
      subsequent farrowing in the second or later service groups were greater than in
      the first service group (P<0.05), but in parity >or=3, the third or later service
      groups produced fewer pigs born alive than the other service groups (P<0.05).
      Lifetime performance and re-service events were observed in 39945 individual
      females on the 149 selected farms that had complete 5-year records. Means of days
      to re-service, first-mating-to-culling intervals in gilts and weaning-to-culling
      intervals in sows were 46.3 days, 95.2 days, and 48.2 days, respectively. Re
      serviced gilts had longer NPD (>50 days), a lower parity at culling (>0.5) and
      fewer lifetime pigs born alive (>2 pigs) than non-return gilts (P<0.05), but no
      difference in average pigs born alive per parity was found between re-serviced
      gilt groups and non-return gilts. Of 19677 re-serviced females, 35.6% had two or
      more re-services across parities in pig life, 10.6% had 3 or more re-services,
      and 1.95% had four or more re-services. Accurate estrus detection with a boar and
      improved mating techniques on re-serviced females are suggested to improve herd
      productivity.

PMID- 14709817
TI  - Conditioned fear-related ultrasonic vocalizations are emitted as an emotional
      response.
AB  - Ultrasonic vocalizations (USVs) are observed along with freezing behavior when
      rats are placed under fearful situation. Coping style with stress is categorized
      into two forms, namely passive and emotional avoidance and active operant
      avoidance. In this study, fear-induced USV was compared between two conditioning
      protocols. Two groups of male Wistar rats were contextually conditioned for 10
      days by exposing to the shock box. One group was shock-unavoidable and the other
      shock-avoidable by operant control of emitting the USVs. They were then proceeded
      to the extinction phase. As the results, the shock-unavoidable group emitted
      greater USV in both conditioning and extinction phases. The extinction burst,
      commonly seen in active learned responses, was not observed in either group. The
      duration of freezing was also longer in shock-unavoidable conditioned rats. These
      results suggest that under the shock-unavoidable condition, rats receive more
      stress and thus emit more USV. It is therefore concluded that fear-induced USV is
      an emotional and passive response to the stress, rather than being controlled in
      an operant-way.

PMID- 14709816
TI  - Expression of estrogen receptor alpha and beta in the uterus and vagina of
      immature rats treated with 17-ethinyl estradiol.
AB  - The action of estrogen on target organs has been actively studied with the
      discovery of estrogen receptor (ER) beta. This study was carried out to examine
      the expression of ERalpha and ERbeta in the uterus and the vagina of immature
      Sprague-Dawley rats treated with 17-ethinyl estradiol (EE). Twenty days old rats
      were subcutaneously treated with EE at the doses of 0 (vehicle control), 0.03,
      0.3, 1.0, 3.0, and 10.0 microg/kg/day for three consecutive days. The treatment
      of EE at the doses of 0.3, 1.0, 3.0 and 10.0 microg/kg/day significantly
      increased the weights of the uterus and vagina of rats (p<0.01) and retained
      fluid in the uterus of rats. At the high doses of 3.0 and 10.0 microg/kg/day, the
      treatment of EE caused an increase in the uterine height, hypertrophy, and a
      decrease in the expression of ERalpha and ERbeta in the uterine luminal and
      glandular epithelium. The treatment of EE at the doses of 3.0 and 10.0
      microg/kg/day also caused cornification and a decrease in the expression of
      ERalpha and ERbeta in the vaginal epithelium. These results suggest that the EE
      treatment decrease the expression of ERalpha and ERbeta in the uterus and vagina
      of immature rats and that may be associated with the morphological changes such
      as increase in the uterine height, hypertrophy of the uterine epithelium, and
      cornification of the vagina.

PMID- 14709818
TI  - Distribution of protein gene product 9.5-immunopositive and NADPH-diaphorase
      positive neurons in the common marmoset (Callithrix jacchus) accessory olfactory
      bulb.
AB  - The principal center of the accessory olfactory system is the accessory olfactory
      bulb (AOB). In primates, simians are divided into two groups, New and Old World
      monkeys, and the AOB is present in only New World monkeys. The common marmoset
      (Callithrix jacchus) is a species of New World monkey. Although the morphology of
      the common marmoset AOB has been demonstrated, the distribution patterns of the
      mitral/tufted and granule cells of the AOB remain unclear. In the present study,
      therefore, the distribution of the mitral/tufted and granule cells in the common
      marmoset AOB was examined using two histochemical markers including immuno
      staining for protein gene product (PGP) 9.5 and NADPH-diaphorase staining. The
      vomeronasal nerves, gomeruli and mitral/tufted cells showed PGP 9.5
      immunoreactivity. The mitral/tufted cells were arranged in only one or two rows
      along the margin of the glomerular layer to form the mitral/tufted cell layer
      (MTL). Since the mitral/tufted cells occurred sparsely in the common marmoset,
      the MTL was illegible. NADPH-diaphorase reactivity was primarily detected in the
      rostral and caudal areas of the AOB. In these areas, granule cells showed NADPH
      diaphorase reactivity. Since the granule cells were sparse, the common marmoset
      AOB displayed less-developed granule cell layer. Although the functional
      significance of the AOB remains to be solved in the common marmoset, small-sized
      and less-laminated AOB may show that sexual behavior of the common marmoset has
      lesser dependence on the accessory olfactory system.

PMID- 14709819
TI  - Rhodococcus equi virulence plasmids recovered from horses and their environment
      in Jeju, Korea: 90-kb type II and a new variant, 90-kb type V.
AB  - Rhodococcus equi was isolated from fecal and soil samples from four native Jeju
      horse farms and six Thoroughbred farms in Jeju, Korea. The isolates were examined
      for the presence of virulence-associated 15-17-kDa antigens (VapA) by colony
      blotting, using the monoclonal antibody 10G5, and for the gene encoding VapA by
      PCR. R. equi was isolated from all 36 soil samples collected from the 10 farms
      with between 5.0 x 10(2) and 7.5 x 10(4) colony-forming units (cfu) per gram of
      soil, and from 37 of 40 fecal samples with between 5.0 x 10(1) and 1.1 x 10 (5)
      cfu per gram of feces. Virulent R. equi was isolated from seven farms and
      appeared in 2.0% of isolates (10 of 508). Of the 10 virulent isolates, four
      contained a 90-kb type II plasmid, which has been found in isolates from the Kiso
      native horses of Japan, and the other six contained a new variant, which did not
      display the EcoRI and EcoT22I digestion patterns of the 10 representative
      plasmids already reported (85-kb types I, II, III, and IV; 87-kb types I and II;
      90-kb types I, II, III, and IV). We designated the new variant as the "90-kb type
      V" plasmid, because its EcoRI digestion pattern is similar to that of the 90-kb
      type II plasmid. This is the first report of the prevalence of virulent R. equi
      in Jeju, Korea. The same virulence plasmid type is found in both Korean and
      Japanese isolates, providing insight into the origin, ancestry, and dispersal of
      native horses in Korea and Japan.

PMID- 14709820
TI  - A comparative pathological study on granulomatous meningoencephalomyelitis and
      central malignant histiocytosis in dogs.
AB  - Histiocytic proliferative disorders in canine central nervous system (CNS)
      including granulomatous meningoencephalomyelitis (GME) and malignant
      histiocytosis were compared pathologically. Lesions of GME mainly existed in the
      white matter of the cerebrum, brainstem and cerebellum and consisted of
      characteristic perivascular cuffing, parenchymal granuloma and leptomeningeal
      infiltrates of mononuclear cells. In malignant histiocytosis, there were two
      histological patterns, diffuse proliferation of neoplastic histiocytes through
      the leptomeninges and neoplastic nodule formation in the parenchyma. Neoplastic
      histiocytes exhibited mild to severe cellular atypia and high ability of invasion
      into the brain parenchyma. Mitotic and phagocytic figures were also observed.
      Several histiocytic markers, including lysozyme, alpha1-antitrypsin and lectin
      RCA-1, revealed histiocytic origin of both inflammatory and neoplastic cells,
      however, those were not determinative for the discrimination between GME and
      malignant histiocytosis. CD3- and PCNA-positive cells existed in the lesions of
      both diseases. The number of CD3-positive cells in GME tended to be greater than
      in malignant histiocytosis, while the difference was not statistically
      significant.

PMID- 14709821
TI  - CD38 gene disruption inhibits the contraction induced by alpha-adrenoceptor
      stimulation in mouse aorta.
AB  - CD38 is an ectoenzyme with ADP-ribosyl cyclase and hydrolase activities, which
      synthesizes cyclic ADP-ribose from NAD and hydrolyzes cyclic ADP-ribose to ADP
      ribose. It has been shown that cyclic ADP-ribose is a potent Ca(2+) mobilizing
      messenger in many cells. To know the physiological role of cyclic ADP-ribose in
      vascular smooth muscle, we examined the effects of various agonists in the aorta
      isolated from CD38 knockout (CD38(-/-)) mouse. Western blot analysis showed that
      CD38 protein was detected in the aorta isolated from wild-type (CD38(+/+)) mouse,
      but not from CD38(-/-) mouse. In the aortae isolated from both CD38(+/+) and
      CD38(-/-) mice, KCl, phenylephrine and norepinephrine induced concentration
      dependent contraction. KCl produced similar concentration-dependent responses in
      the aortae from both CD38(+/+) and CD38(-/-) mice. Maximum force of contraction
      induced by KCl (65 mM) was same in the size. Phenylephrine- and norepinephrine
      induced contractions were, however, significantly smaller in the aortae from
      CD38(-/-) mice than in those from CD38(+/+) mice. 5-Hydroxytryptamine, endothelin
      1, caffeine and thapsigargin-induced contractions were not significantly
      different in these two aortae. These results suggest that CD38 gene disruption
      inhibits alpha-adrenoceptor-induced vascular contractions and cyclic ADP-ribose
      mediated signal transduction system is committed in these responses.

PMID- 14709822
TI  - Spermatogenetic disorders in adult rats exposed to tributyltin chloride during
      puberty.
AB  - Adverse effects of tributyltin (TBT) chloride were investigated on the
      reproductive system in male adult rats as exposed during puberty. Fifty Sprague
      Dawley rats at the age of 35 days were assigned to five different groups:
      negative control receiving vehicle, methyltestosterone (10 mg/kg B.W.), and TBT
      chloride treatments (5, 10, and 20 mg/kg B.W.). Animals were treated by oral
      gavage for ten consecutive days and sacrificed at 5 weeks after final treatment.
      The treatment of TBT chloride at the high dose of 20 mg/kg B.W. significantly
      decreased homogenization-resistant testicular sperm counts (p<0.05). The TBT
      chloride treatment at the doses of 10 and 20 mg/kg B.W. also significantly
      decreased caudal epididymal sperm counts (p<0.01). Some of motion kinematic
      parameters (motility, mean angular displacement, lateral head displacement, and
      dance) of sperms retrieved from vasa deference were significantly decreased in
      rats treated with the TBT chloride at the dose of 20 mg/kg B.W. (p<0.05). These
      results provide a further evidence that an exposure to TBT chloride during
      pubertal period in male rats produces spermatogenic disorders characterized by
      decreasing testicular and epididymal sperm counts and some motion parameters of
      sperms in the vasa deference.

PMID- 14709823
TI  - Adjuvant effect of chicken interferon-gamma for inactivated Salmonella
      Enteritidis antigen.
AB  - The adjuvant effect of chicken interferon-gamma (ChIFN-gamma) was examined for
      protecting chickens against intestinal colonization of Salmonella Enteritidis
      (SE) following oral exposure. Ten 7-week-old chickens per group were immunized
      with inactivated SE twice with or without co-administration of ChIFN-gamma
      intramuscularly, and all chickens were challenged with SE. Sera collected from
      immunized groups with or without ChIFN-gamma, and from unimmunized group were
      measured for SE antibody by agglutination test. The levels of antibodies were
      raised by 1 week post-immunization and did not show any difference between groups
      with and without ChIFN-gamma. No antibodies were detected in unimmunized group
      before challenge. Fecal samples from each group were cultured at 1, 4, 7, and 13
      days post-challenge to determine the incidence of intestinal colonization and the
      numbers of SE shed into the environment. Co-administration of ChIFN-gamma,
      significantly reduced the incidence of intestinal colonization (P<0.05). At 13
      days post-challenge, the bacterial counts of SE in organs were also reduced in
      ChIFN-gamma administered group. These data suggest co-administration of ChIFN
      gamma with SE antigen enhances protection against SE challenge without
      acceleration of antibody production.

PMID- 14709824
TI  - Therapeutic effect of aromatase inhibitor in two azoospermic dogs with high
      plasma estradiol-17beta levels.
AB  - Two azoospermic dogs with high plasma estradiol-17 beta (E(2)) levels were
      subcutaneously injected with an aromatase inhibitor (AI), 4-androstene-4-ol-3,17
      dione, 2 mg every other day for 4 weeks. Before the AI treatment the plasma E(2)
      levels of the two dogs (21 and 22 pg/ml, respectively) were higher than those of
      2 normal dogs (8.1 and 12.3 pg/ml), and they fell to 11-17 pg/ml between 1 and 4
      weeks after the start of AI treatment. The plasma testosterone levels after the
      start of AI treatment had increased to 2.1-3.1 ng/ml. A small number of sperm
      were detected in the semen of the two dogs between 3 and 6 weeks after the start
      of AI treatment. These results indicate that the testicular function of infertile
      dogs with high plasma E(2) levels can be temporarily improved by AI therapy.

PMID- 14709825
TI  - The influence of early weaning on aggressive behavior in mice.
AB  - Early postnatal experiences have been shown to have a tremendous influence on
      behavior development. In this study, we focused on weaning time and investigated
      the effects of early weaning on adulthood aggressive behavior in mice with the
      resident-intruder test. Early weaning resulted in decreased sideways threat and
      tail rattle. In addition, the frequency of attack bites was more variable in the
      early weaned group, although the mean frequency did not differ from the normally
      weaned group. The results of the present study suggest that aggressive behavior
      is also affected by early weaning manipulation.

PMID- 14709826
TI  - Molecular cloning and expression of bottlenose dolphin (Tursiops truncatus)
      interleukin-8.
AB  - The bottlenose dolphin interleukin (IL)-8 cDNA was molecularly cloned. The
      dolphin IL-8 has an open reading frame of 303-bp encoding 101 amino acids. The
      homology of the amino acid sequence with that of other species was: sheep, 89.1%;
      cattle, 88.1%; pig, 85.1%; dog, 85.1%; horse, 79.2%; human, 74.5%; and macaque,
      72.3%. The amino acid sequence suggested that dolphin IL-8 was a CXC chemokine.
      The recombinant dolphin IL-8 protein was recognized with anti-ovine IL-8
      monoclonal antibody.

PMID- 14709827
TI  - Cytokine and inducible nitric oxide synthase gene expressions in peripheral blood
      mononuclear cells and related clinical characteristics in Theileria orientalis
      sergenti-infected calves.
AB  - Eight splenectomized calves were inoculated with Theileria orientalis sergenti
      (Tos)-infected tick gland homogenate (5 calves) or infected erythrocyte
      suspension (3 calves). Clinical characteristics were different in calves post
      infection. Animals were divided into 3 groups on the basis of susceptibility as
      high, middle, and low. Increase in mRNA of IFN-gamma, IL-2, and TNF-alpha was
      observed in peripheral blood mononuclear cells at the peak of infection and was
      seen to be related with pyrexia and parasitemia. Expression of IL-1, IL-4, and
      inducible nitric oxide synthase was not observed. Decreased plasma
      nitrite/nitrate level was observed in the groups. The results of this study
      indicate that Th1 response is the predominant response in Tos infection, and this
      response is also related with their clinical characteristics.

PMID- 14709828
TI  - Hydrocephalus with visual deficits in a cat.
AB  - A 22-month-old male Japanese mongrel cat with a history of dysuria and recurrent
      generalised tonic-clonic seizure was examined by neuro-opthalmological testing
      and computed tomography (CT). Vision testing revealed narrowing of the visual
      field in the right eye, and complete visual deficits in the left eye. Pupillary
      reactions, and motor and sensory function in the eyelids and the eyes were
      normal. The cat was diagnosed as hydrocephalus by CT examination, because
      dilation of the right lateral ventricle, and compression of the right temporal
      and occipital cortices was shown. The etiology of the hydrocephalus was unclear.
      Although a unilateral lesion of the upper visual pathway was suspected, a
      complete homonymous hemianopsia was not shown.

PMID- 14709829
TI  - Usefulness of infrared thermometry in determining body temperature in mice.
AB  - The rectal temperature obtained using a standard electronic thermometer was
      compared with ear, back skin, tail skin, and sole skin temperatures obtained
      using an infrared thermometer in B6C3F1 mice. Using both methods, we investigated
      baseline temperatures, diurnal and 2-week variations in temperatures, and ethanol
      induced hypothermia in these body locations. Ear and back temperatures were shown
      to be close to and consistent with rectal temperatures in various situations, and
      measured temperatures at these sites were almost constant, with very similar
      diurnal variation. Conversely, tail and sole temperatures were lower and much
      more variable. These results indicate that ear and back skin temperatures
      obtained using a convenient and non-invasive infrared thermometer are as
      reliable, and should be safer and less stressful to animal subjects, compared to
      standard rectal temperature measurements.

PMID- 14709830
TI  - Comparison of the effects of isotonic and hypertonic sodium bicarbonate solutions
      on acidemic calves experimentally induced by ammonium chloride administration.
AB  - The objectives of this study were to evaluate and compare the effects of
      intravenously (IV) administered infusion of isotonic solution (ISB) or hypertonic
      sodium bicarbonate solution (HSB) on acid-base equilibrium and the plasma
      osmolarity in acidemic calves experimentally induced by 5 M-NH(4)Cl, IV infusion
      (1.0 ml/kg, over 1 hr). The ISB and HSB infusion induced progressive and
      significant increases in their HCO(3)(-) and BE levels that persisted throughout
      the period of fluid administration. The plasma osmolarity in the ISB groups was
      significantly decreased. The plasma osmolarity in the HSB group was significantly
      higher than in the calves in the other groups (p<0.05). ISB solution might be
      safe and effective for treating and reviving conscious calves from experimentally
      induced metabolic acidosis.

PMID- 14709831
TI  - Temporal dynamic changes in synthesis of chondroitin sulfate isomers in canine
      articular chondrocyte culture.
AB  - To investigate temporal dynamic changes in the synthesis of chondroitin 6-sulfate
      (CS6) and chondroitin 4-sulfate (CS4) in vitro, normal articular cartilage of
      femoral heads was harvested from three dogs. Chondrocytes were isolated and
      cultured in alginate microspheres for 21 days. On days 7, 14 and 21, DNA content
      was quantified by fluorometric assay using Hoechst 33258. On days 14 and 21,
      proteoglycans were extracted, and the amounts of CS6 and CS4 were quantified
      after chondroitinase ABC digestion using capillary electrophoresis. The DNA
      content and amounts of CS6 and CS4 increased during the culture period. The
      amounts of CS6 and CS4 divided by DNA content revealed that the synthesis of CS6
      was more up-regulated than CS4.

PMID- 14709832
TI  - The detection of bovine lactoferrin binding protein on Toxoplasma gondii.
AB  - Lactoferrin (LF), a member of the transferrin (TF) protein family, is an iron
      binding protein that is known to interact with bacteria through a specific
      receptor. We examined the binding of bovine LF (bLF), bovine TF (bTF), and
      ovotransferrin (OTF) by Toxoplasma gondii using a fluorescence test and the
      streptavidin-biotin (SAB) method using biotin-streptavidin, and found that bLF,
      bTF, and OTF bound to the protein components of T. gondii. Furthermore, we
      confirmed that bLF, bTF, and OTF bound a 42 kDa soluble protein of T. gondii by
      far Western blot method. These results demonstrated that bLF binding proteins are
      present on T. gondii.

PMID- 14709833
TI  - A case of a ruptured pheochromocytoma with an intratumoral aneurysm managed by
      coil embolization.
AB  - Although the spontaneous rupture of adrenal pheochromocytoma is rare, it can be
      lethal because it can induce serious changes in the circulation. We describe a 32
      year old man with bilateral pheochromocyroma presenting as abdominal pain. In the
      emergency room, an abdominal MRI showed an aneurysmal vessel in the right adrenal
      mass and accompanying hemorrhage around the tumor capsule. The bleeding site was
      found by transfemoral abdominal angiography. Coil embolization was done in the
      bleeding vessels, specifically branches of the right adrenal artery. The
      hemorrhage was successfully controlled and vital signs of the patient were
      restored. Following emergency care, biochemical and imaging studies showed
      compatible findings of a bilateral adrenal pheochromocytoma. Postoperative
      histologic findings confirmed these observations. A ruptured pheochromocytoma
      should be considered as a cause of acute abdomen in cases of a concomitant
      adrenal mass. Intratumoral aneurysmal bleeding may be a cause of ruptured tumor,
      and careful angiographic intervention will help to ensure safe control of
      bleeding in such an emergency situation, even in cases of bilateral tumor.

PMID- 14709834
TI  - Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and
      hypothyroidism.
AB  - Bone turnover is reported to increase in favour of resorption in overt
      hyperthyroidism and the rate of resorption is associated with the levels of
      thyroid hormones. Hypothyroidism, on the other hand, was shown to cause no
      disturbance of calcium kinetics and found to associate lower trabecular
      resorption surfaces and increased bone cortical thickness. Similar studies are
      very rare in subclinical thyroid disorders and consequently we aimed to examine
      calcium and bone metabolism in subclinical thyroid disorders. Thirteen patients
      with subclinical hyperthyroidism secondary to untreated Graves' disease, 20
      patients with subclinical hypothyroidism and 10 healthy subjects participated in
      this survey. Briefly calcium, phosphorus, and creatinine (Cre), urinary
      deoxypyridinoline (U-DPD) and serum osteocalcin (OC) were measured as biochemical
      markers for calcium metabolism. Concerning serum Ca and phosphorus levels, there
      were no differences between three of the groups, but urinary Ca excretion was
      higher in subclinical hyperthyroid patients compared to control and hypothyroid
      subjects. Hypothyroid patients had similar U-DPD levels with control subjects (p
      = 0.218). Serum OC and U-DPD were higher in subclinical hyperthyroid compared to
      control subjects (p<0.001 and p<0.001 respectively). We demonstrated a higher
      bone turnover and greater calcium excretion in subclinical hyperthyroid patients.
      Additionally, we found that subclinical hypothyroidism is not associated with
      disturbed calcium metabolism. As persistent increase in bone turnover is
      responsible for accelerated bone loss, patients with Graves' disease may have
      increased risk for osteoporosis.

PMID- 14709835
TI  - Alveolar gas exchange in patients with type 2 diabetes mellitus.
AB  - The present study has been conducted to quantify and compare the capacity of gas
      exchange in patients with type 2 diabetes mellitus (DM) and healthy controls and
      also to investigate the effects of various factors on alveolar capillary
      permeability. A total of 37 subjects, 25 patients with DM and 12 healthy controls
      were recruited for the study. All the participants were evaluated with simple
      spirometric tests and simple breath carbonmonoxide (CO) diffusion test (DLCO).
      The ratio of DLCO value to the alveolar ventilation (VA) was used to assess
      alveolar membrane permeability. Diabetic patients were also evaluated in detail
      with respect to degenerative diabetic complications including the presence of
      microalbuminuria, advanced nephropathy, sensorial and autonomic neuropathy,
      retinopathy, hypertension and macrovascular disease. The results of simple
      spirometric tests which determined lung capacity were similar in the diabetic
      patients and the healthy controls. Ratio of DLCO/VA, which determines alveolar
      membrane permeability, revealed statistically significant decline in pulmonary
      gas exchange in the diabetic group (p: 0.037). Pearson correlation analysis
      revealed statistically significant correlation between duration of diabetes
      mellitus, age and urinary albumin excretion with DLCO/VA values (Pearson: -0.726,
      p: 0.001; Pearson: -0.438, p: 0.036; Pearson: -0.472, p: 0.023 respectively).
      This study demonstrated the decreased alveolar gas exchange capacity in diabetic
      patients compared with healthy controls. Detrimental effects of DM on alveolar
      capillaries were found to be correlated with age, duration of DM and urinary
      albumin excretion. Microalbuminuria was the only significant predictor of
      DLCO/VA.

PMID- 14709836
TI  - Seasonal variation in relapse rate of graves' disease after thionamide drug
      treatment.
AB  - OBJECTIVE: Controversy abounds on the issue of seasonal variation in new onset of
      Graves' disease, partly due to the difficulty of precisely dating the exact start
      of symptoms. To address the possible relationship between climatic changes and
      disease activity from a different perspective, we reviewed time of relapse during
      regular follow-up after successful drug treatment with thionamides. DESIGN:
      Retrospective analysis of a case series in a university clinic. PATIENTS AND
      MEASUREMENTS: We consecutively registered patients who experienced re-emergence
      of hyperthyroidism between 1992 and 2001 after successful antithyroid drug
      therapy. Excluded were subjects with superimposing painless thyroiditis, in
      postpartum, on immunomodulatory drugs, or off thionamides prematurely on their
      own volition. RESULTS: Fifty-two patients recurred 2 to 36 months after drug
      cessation. The frequency was higher in spring and summer (March to August) than
      in autumn and winter (September to February). With a new coated-tube
      radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected
      in sera from 87.5% of the reworsened patients. CONCLUSIONS: Graves' disease tends
      to relapse more frequently in spring and summer. Further clinical studies are
      warranted to clarify underlying mechanism (s) for this seasonal variation.

PMID- 14709837
TI  - The effect of leptin, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide
      (NO) production on insulin resistance in Otsuka Long-Evans fatty rats.
AB  - Adipocytokines and nitric oxide (NO) play important roles in type 2 diabetes;
      however, the regulatory mechanism has not been fully clarified. To investigate
      the role of adipocytokines and NO production on insulin resistance in type 2
      diabetes, the LETO rats and the OLETF rats were fed a control diet or a high-fat
      diet for 4 weeks. After 4 weeks the blood levels of leptin, tumor necrosis factor
      alpha (TNF-alpha), and NO were measured. As an indicator of insulin resistance,
      the homeostasis model assessment for insulin resistance (HOMA-R) was applied.
      Food intake in high-fat diet group rats was lower than in control diet group
      rats. The high fat diet increased body weight (BW), but did not significantly
      affect the HOMA-R and blood pressure (BP). Leptin and TNF-alpha levels were
      significantly higher in the OLETF rats than in the LETO rats, while NO levels did
      not change between the two groups. The high-fat diet elevated blood leptin
      levels, but not TNF-alpha and NO levels. The HOMA-R in the OLETF rats was
      correlated with leptin, but not with BP, BW, TNF-alpha or NO. NO showed an
      inverse correlation with BP. In conclusion, leptin, TNF-alpha, and NO may each
      regulate insulin sensitivity through their own unique pathways. The elucidation
      of the regulatory mechanism of adipocytokines and NO may give a clue to clarify
      the pathophysiology of insulin resistance.

PMID- 14709838
TI  - Effect of treatment with oral calcitriol on calcium metabolism and fasting serum
      25(OH)- or 1,25(OH)2-vitamin D level in Japanese postmenopausal women.
AB  - The aim of this study was to investigate the effect of daily oral administration
      of calcitriol on calcium metabolism in Japanese postmenopausal women. For this
      purpose, we administered 0.5 microg of daily calcitriol to 18 Japanese
      postmenopausal women for up to 24 weeks. During the first 28 days, daily
      administration of 0.5 microg of oral calcitriol increased fasting serum 1,25(OH)
      2D levels significantly in 9 women (Group B) (p<0.005), while no significant
      change was seen in another 9 women without calcitriol administration (Group A).
      The first 28-day calcitriol supplement increased fasting urinary calcium
      excretion (urinary Ca/Cr) from 0.133 +/- 0.072 to 0.171 +/- 0.089 (p<0.05) and
      fractional excretion of calcium (FECa) without changing serum Ca2+. Urinary
      NTx/Cr excretion, an index of bone resorption, decreased significantly from 64.8
      +/- 24.5 to 50.3 +/- 27.2 nMBCE/mMCr in Group B. Following the 28-day control
      period, 0.5 microg of oral calcitriol was also administered to women in Group A
      for another 20 weeks. At the end of the 24-week investigation period, the effects
      of oral calcitriol on urinary calcium excretion and bone resorption were still
      significant in both Group A and B. A positive correlation was found between
      urinary Ca/Cr and NTx/Cr excretion at the start (r = 0.657, p<0.05), but this
      correlation was lost by calcitriol treatment (r = 0.135). These results indicated
      that calcitriol supplement was effective in suppressing bone resorption in
      postmenopausal women, and that an increased fasting urinary calcium excretion due
      to calcitriol supplement was predominantly caused by increased intestinal calcium
      absorption in these women.

PMID- 14709839
TI  - The effect of physiologic hyperinsulinemia during an oral glucose tolerance test
      on the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in healthy
      young adults born with low and with normal birth weight.
AB  - Several data support that adrenal hyperandrogenism affects women with low birth
      weight (LBW). We also found an association between serum dehydroepiandrosterone
      (DHEA) and fasting insulin levels. The aim of our study was to detect the acute
      effects of reactive hyperinsulinemia during oral glucose tolerance test (OGTT) on
      DHEA(S) levels in LBW men and women. Fifty three men and 47 women (of those, 37
      men and 33 women were LBW) were enrolled. DHEA, DHEAS, and insulin levels were
      measured before and during OGTT. Cortisol was also measured. DHEA/cortisol ratio
      during OGTT was calculated to analyze the acute effect of hyperinsulinemia on
      DHEA levels. During OGTT, DHEA and cortisol levels decreased in each individual,
      independently of gender and birth weight. Serum DHEAS decreased to a minor (but
      significant) extent only in LBW women (p<0.05). The rate of DHEA/cortisol
      increased in both gender, independently of birth weight. The increase of the rate
      of DHEA/cortisol during OGTT was associated with maximal insulin response (r =
      0.45, p<0.05) and with the insulin(AUC) (r = 0.48, p<0.05) in women. Our results
      suggest that reactive hyperinsulinemia during OGTT might activate the androgen
      pathway of adrenal cortex including DHEA production. Therefore acute
      hyperinsulinemia might counterbalance to some extent the diurnal decrease of DHEA
      during OGTT.

PMID- 14709840
TI  - Anti-alpha-enolase antibodies in pituitary disease.
AB  - A previous study reported a high prevalence of autoantibodies to alpha-enolase in
      lymphocytic hypophysitis and these antibodies efficiently distinguished
      lymphocytic hypophysitis from pituitary tumors. To confirm this, we examined
      autoantibodies to alpha-enolase in patients with lymphocytic hypophysitis (n =
      17), pituitary non-functioning adenoma (n = 13), other pituitary diseases (n =
      17) and other autoimmune diseases (n = 30), and compared to healthy controls (n =
      46). Autoantibodies were found in 41.2%, 46.2%, 23.5%, 20.0% and 4.3%,
      respectively. Our findings indicate that detection of anti-alpha-enolase
      antibodies is not suitable for specific diagnosis of lymphocytic hypophysitis.

PMID- 14709841
TI  - Epidermal growth factor enhances invasive activity of BeWo choriocarcinoma cells
      by inducing alpha2 integrin expression.
AB  - The trophoblast, an important component of the mammalian placenta, has several
      essential biological roles in the maintenance of pregnancy. First, trophoblast
      cells must attach to the uterine endometrium, and then they must invade to a
      depth at which the vascular network exists. Here, we investigated the effects of
      epidermal growth factor (EGF) on alpha2 integrin expression, adhesiveness to
      collagen, and invasive activity using human BeWo choriocarcinoma cells. EGF
      induced the expression of alpha2 integrin mRNA and protein, as shown by Northern
      blotting, Western blotting, and flow cytometry. Human chorionic gonadotropin
      (hCG) secretion was enhanced by the addition of EGF, which suggests that the BeWo
      cells functionally differentiated similarly to normal trophoblasts. EGF also dose
      dependently stimulated the invasiveness of BeWo cells. Antibody against alpha2
      integrin inhibited this effect, suggesting that it may be mediated by an increase
      of cell surface integrin. EGF had no effect on the adhesiveness of BeWo cells to
      collagen, whereas it stimulated the chemokinetic activity in a dose-dependent
      manner. The increase of chemokinetic activity was suppressed by antibody against
      alpha2 integrin. These results suggest that EGF may induce alpha2 integrin
      expression in trophoblast cells, thereby enhancing their invasiveness into the
      endometrium via an increase of their chemokinetic activity.

PMID- 14709842
TI  - Unilateral adrenalectomy improves insulin resistance and diabetes mellitus in a
      patient with ACTH-independent macronodular adrenal hyperplasia.
AB  - ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of
      Cushing's syndrome. Bilateral adrenalectomy is considered to be a standard
      therapy for AIMAH, although lifetime replacement of glucocorticoids is necessary
      after the procedure. This paper describes a subject with AIMAH who underwent
      unilateral adrenalectomy of the predominantly enlarged gland and subsequently
      displayed an improvement in insulin resistance and diabetes mellitus, the
      cardinal symptoms before the operation, concomitant with alleviation of abnormal
      cortisol secretion. The patient was a 61-year-old man with a body mass index of
      25.6 kg/m2. He was diagnosed as having diabetes mellitus, hypertension, and
      hyperlipidemia at 50 years of age. Eight years after diagnosis, bilateral
      enlargement of the adrenal glands was revealed by chance upon computed tomography
      of the abdomen. Typical manifestations of Cushing's syndrome were not
      demonstrated. Basal levels of serum and urinary cortisol had not increased,
      although the serum cortisol level displayed no circadian rhythm and no response
      to the administration of dexamethasone. Despite sulfonylurea treatment, the
      patient's HbA1C level was as high as 7.6% (normal range 4.3-5.8%). Fasting
      insulin concentration was increased to 42.6 microU/ml, and the homeostasis model
      insulin resistance index (HOMA-R) was calculated to be 15.5 (with a normal range
      of less than 2.5), indicating severe insulin resistance. Unilateral adrenalectomy
      of the predominantly enlarged gland revealed that the resected gland consisted of
      multiple nodules of various sizes. Based on endocrinological, radiological, and
      pathological findings, a diagnosis of AIMAH was made. Ten months after the
      unilateral adrenalectomy, cortisol circadian rhythms were restored, and serum
      cortisol concentration was suppressed in response to the administration of low
      doses of dexamethasone, suggesting an improvement in the cortisol secretory
      pattern. Levels of HbA1C, fasting insulin, and HOMA-R decreased to 5.7%, 12.7
      microU/ml, and 2.2, respectively. An improvement in hyperlipidemia was also
      observed. Insulin resistance and glucose intolerance are recognized as features
      of mild hypercortisolism. In the present case, unilateral adrenalectomy was
      effective in ameliorating insulin resistance and improving glycemic control.
      Unilateral adrenalectomy might be an alternative therapy for improvement of
      glucose and lipid metabolism in subjects with AIMAH.

PMID- 14709843
TI  - Comparison of different thyroidectomy techniques for benign thyroid disease.
AB  - Extent of thyroidectomy in the management of benign thyroid disease remains
      controversial. In this clinical study, three different thyroidectomy techniques
      were compared by means of the complication, short period recurrence and L
      thyroxin requirement rates. Two hundred consecutive patients who had bilateral
      subtotal thyroidectomy (BST) (n = 71), unilateral total lobectomy + contralateral
      subtotal lobectomy (Dunhill Procedure (DP)) (n = 71), or total thyroidectomy (TT)
      (n = 58) for benign thyroid disorders were included in this study. One patient
      was re-operated due to bleeding in BST group. Wound infection was observed in 1
      patient both in BST and DP group and 2 patients in TT group. Temporary
      hypocalcaemia was seen in 14 (19.7%) of BST group, in 19 (26.7%) of DP group, and
      in 14 (24.1%) patients of TT group (p>0.05). Transient recurrent laryngeal nerve
      palsy developed in 1 patient both in DP and TT group. One patient of DP group had
      secondary thyroidectomy due to postoperative diagnosis of papillary carcinoma.
      There was no significant difference in the mean durations of hospitalization
      between the groups. Mean postoperative follow-up periods were 27.7 months (6-56),
      34.8 months (8-55), 26.5 months (6-54) in BST, DP and TT groups, respectively.
      While all patients were administered L-thyroxin in TT group, 26 (36.6%) patients
      in DP group and 34 (47.8%) patients in BST group needed no L-thyroxin
      supplementation and L-thyroxin requirement rates were not different in either
      group. We think that total thyroidectomy should be adopted for benign thyroidal
      diseases, because its complications are no different than those for BST and DP.
      If individual factors and patient's preference are not in favor of lifelong L
      thyroxin supplementation, however, DP may be carried out for benign thyroidal
      diseases instead of BST.

PMID- 14709844
TI  - Changes in anthropometry with testosterone therapy in a female with gender
      identity disorder.
AB  - A 31-year-old regularly menstruating Japanese female was referred to our
      outpatient clinic by a psychiatrist. She had been diagnosed as having gender
      identity disorder by detailed counseling and clinical intervention 3 years
      earlier. After obtaining fully informed written consent, we treated her with 125
      mg of testosterone enanthate, intramuscularly, every 2 weeks for 4 months. Serum
      testosterone levels increased to the normal male value (from 28 to 432 ng/dL).
      Although menstrual cycle remained regular, her voice became lower after 4 months
      of therapy. Body weight, body mass index, and lean body mass increased, while
      body fat mass and percentage of body fat decreased. However, trunk-leg fat ratio
      did not change during the observation period. During testosterone therapy, a
      disproportionate increase in lean body mass and decrease in body fat mass are
      early onset events, while the shift toward upper body fat distribution may be a
      late onset event along with increase in BMD.

PMID- 14709845
TI  - Fertile eunuch syndrome with the mutations (Trp8Arg and Ile15Thr) in the beta
      subunit of luteinizing hormone.
AB  - Fertile eunuch syndrome is caused by isolated LH deficiency, but its
      pathophysiology still remains controversial. We report a case of fertile eunuch
      syndrome with homozygous Trp8Arg and Ile15Thr mutations in the LH beta subunit
      gene. An 18-year-old man was admitted to our hospital for hypogonadism.
      Examination of genitalia revealed Tanner G1PH1, whereas both testes were
      elastically palpated and developed up to 18 ml. Endocrinological evaluations
      revealed normogonadotropic hypogonadism and there were normal responses after
      GnRH and hCG stimulation. Intratesticular testosterone concentration was almost
      normal (1.34 x 10(3) ng/g). By PCR direct sequencing, homozygous Trp (8) Arg and
      Ile (15) Thr mutations in exon 2 of LH beta were detected. Normal virilization
      and improved semen parameters were achieved after hCG supplementation. To our
      knowledge, this is the first case of fertile eunuch syndrome with homozygous Trp
      (8) Arg and Ile (15) Thr mutations in beta subunit of LH gene.

PMID- 14709846
TI  - A case of ACTH-producing pheochromocytoma associated with pregnancy.
AB  - Ectopic ACTH syndrome is rarely caused by pheochromocytoma. We report a case of a
      28-year-old woman with Cushing's syndrome due to ACTH-producing adrenal
      pheochromocytoma. She had delivered preterm baby at 32nd week of gestation with
      'severe preeclampsia'. After delivery, persistent hypertension accompanied by
      severe headache led her to being misdiagnosed as Cushing's syndrome due to right
      adrenal adenoma (normal plasma ACTH level) and cerebral vasculitis of unknown
      etiology. She was referred to our hospital for surgical treatment. Repeated
      biochemical studies suggested coexistence of ectopic ACTH syndrome and
      pheochromocytoma. To reverse her clinical deterioration, right total and left
      subtotal adrenalectomy was performed with presumptive diagnosis of 1) right
      adrenal pheochromocytoma causing ectopic ACTH syndrome or 2) coexistence of ACTH
      dependent Cushing's syndrome and right adrenal pheochromocytoma. Pathologic
      examination of right adrenal mass revealed pheochromocytoma which showed strong
      immunostaining for ACTH. Plasma ACTH and urinary cortisol excretion normalized
      after surgery, but she succumbed to multiple cerebral infarcts and disseminated
      intravascular coagulation. Pregnancy and inappropriately low plasma ACTH at
      initial evaluation might have hampered early diagnosis. To our knowledge, this is
      the first description of a case with ectopic ACTH syndrome due to
      pheochromocytoma associated with pregnancy.

PMID- 14709847
TI  - Risk factors for adrenal crisis in patients with adrenal insufficiency.
AB  - Patients with adrenal insufficiency have a life-threatening risk of adrenal
      crisis, thus preventing adrenal crisis is an important clinical issue. In order
      to clarify the risk factors for adrenal crisis, the medical records of 137
      patients with established adrenal insufficiency were retrospectively
      investigated. The explanatory variables analyzed were gender, etiology of
      hypoadrenalism, class of adrenocortical hormone replaced, duration of steroid
      replacement, age at time of survey, age at time of diagnosis of hypoadrenalism,
      state of other hormone deficiencies (growth hormone and sex steroids), diabetes
      insipidus, and mental disorder. Diagnosis of adrenal crisis was based on physical
      and laboratory findings. Forty (29%) of the 137 patients had at least one episode
      of adrenal crisis. Based on the Akaike Information Criterion (AIC), steroid
      replacement therapy of more than 4 yrs' duration was the largest single
      contributor to the occurrence of an adrenal crisis, followed by mental disorder
      and sex steroid deficiency. In the subclass of patients with secondary adrenal
      insufficiency (N = 115), sex steroid deficiency was the greatest risk factor.
      Patients with untreated hypogonadism had a significantly higher relative risk of
      3.70 (95% confidential interval: 1.71-7.98) compared to those without
      hypogonadism or with treated hypogonadism. Furthermore, among patients with
      hypogonadism aged younger than 50 yrs, those treated with sex hormone (5/51: 10%)
      suffered less frequently from adrenal crisis than those untreated (7/11: 64%, p =
      0.0004). In conclusion, the present study has, for the first time, clarified the
      risk factors of adrenal crisis. Among them, sex hormone deficiency has an
      especially important implication because it can be treated by hormone replacement
      therapy with the hope of reducing the risk of adrenal crisis.

PMID- 14709848
TI  - Hypoglycemia associated with big insulin-like growth factor II produced during
      development of malignant fibrous histiocytoma.
AB  - We describe a rare case of hypoglycemia associated with a high molecular weight
      form of insulin-like growth factor II (big IGF-II) produced during the
      development of malignant fibrous histiocytoma (MFH). A 66-year-old man was
      referred to our department for further evaluation of hypoglycemia. At the age of
      59, he had been diagnosed as having a MFH in the retroperitoneum, and underwent
      incomplete resection of the tumor. He had no symptoms of hypoglycemia at that
      time. Within the last few years, he developed symptoms of hypoglycemia in the
      early morning. Computerized tomography scans of the abdomen showed multiple
      tumors around the peritoneum and the liver. Serum insulin levels were decreased
      although no other hormonal deficiencies were observed. Serum IGF-II levels were
      elevated as a result of big IGF-II production. Taken together, these results
      indicated that hypoglycemia in this patient was associated with the production of
      big IGF-II by the MFH. The most effective therapeutic modality in patients with
      non-islet cell tumor hypoglycemia is resection of the tumor. In our case, as
      complete resection was impossible, dexamethasone and glucagon were administered
      and proved to be effective for preventing hypoglycemia.

PMID- 14709849
TI  - Hypercholesterolemia and obesity in adult patients with hypopituitarism: a report
      of a nation-wide survey in Japan.
AB  - Dyslipidemia and obesity are common in adult patients with hypopituitarism.
      Possible contributions of age, sex and hormone deficiencies to
      hypercholesterolemia and obesity in adult hypopituitary patients were analyzed in
      1, 272 Japanese cases based on a database of a national survey on adult
      hypopituitarism. In patients on routine hormone replacement therapy, 30.5% of
      male and 40.7% of female subjects were considered hypercholesterolemic. In
      univariate analysis, hypercholesterolemia was more prevalent in female, aged,
      untreated Gn-deficient and TSH-deficient groups. In multivariate analysis, sex of
      female, age older than 40 yr and TSH deficiency were the independent contributing
      factors to hypercholesterolemia. Obesity (body mass index (BMI) > or = 25 kg/m2)
      was more prevalent in male, TSH-deficient and ADH-deficient groups. Severe
      obesity (BMI > or = 30) was observed in high prevalence in the youngest group.
      These findings suggest that hypercholesterolemia and obesity were prevalent in
      different age and gender groups in Japanese adult patients with hypopituitarism.
      Insufficient replacement of thyroid hormone and possibly gonadotropin deficiency
      might contribute to hypercholesterolemia. In contrast, hypothalamic dysfunction
      as well as hormone deficiencies might play roles in obesity in these patients.

PMID- 14709850
TI  - Relapse of Graves' disease in a patient with pheochromocytoma.
AB  - We describe a patient with right adrenal tumor detected incidentally. The tumor
      was diagnosed as pheochromocytoma by endocrinological and radiological studies,
      and was removed surgically. Graves' disease, which had been in remission for more
      than two decades after discontinuation of antithyroid drug treatment, relapsed
      during preoperative evaluation of pheochromocytoma when the patient was treated
      with alpha- and beta1-adrenergic antagonists. Administration of methimazole
      resulted in a rapid improvement of thyroid function and the patient remained
      euthyroid on small doses of methimazole. This case may suggest possible
      involvement of excessive catecholamine secretion and beta2-adrenergic receptor
      activation by pheochromocytoma in the relapse of Graves' disease.

PMID- 14709851
TI  - Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549
      cell growth through activation of p21(WAF1/CIP1 ).
AB  - Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4
      cells. This gene was able to induce cell transformation in vitro and is also
      associated with p53-dependent and -independent apoptosis. In this study, we
      cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the
      hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly
      inhibited cell growth, which was determined by the adherent cell growth
      properties, colony formation in soft agar and [3H] thymidine incorporation,
      respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was
      associated with the activation of p21WAF1/CIP1 in A549 cells, but not in HeLa
      cells. The hPTTG overexpression increased both the p21WAF1/CIP1 mRNA and protein
      expression levels as determined by both Northern and Western blot analysis,
      respectively, in A549 cells. The increased expression of p21WAF1/CIP1 mRNA was
      regulated at the transcription level and was independent on p53 expression
      because the luciferase activity increased after the co-transfection of hPTTG and
      p21WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The
      subcellular distribution of hPTTG was dependent on cell type, and was
      predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse
      distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells.
      These results indicate that an overexpression of hPTTG inhibits the cell growth
      due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent.

PMID- 14709852
TI  - Reference values for urinary steroids in Japanese newborn infants: gas
      chromatography/mass spectrometry in selected ion monitoring.
AB  - Urinary steroid profile analysis using gas chromatography/mass spectrometry
      (GC/MS) has been reported for the diagnosis of abnormal steroidogenesis in
      newborn infants with some success. We tried to establish the reference values of
      63 urinary steroids in Japanese newborn infant, using GC/MS in selected ion
      monitoring (SIM) that utilizes two characteristic mass ions for each steroid for
      definitive identification. We studied 36 healthy full-term newborn infants (1-56
      days of age) on spot urine samples to define the reference values (mg/g
      creatinine, median and 10-90 percentile range) and to investigate the possible
      difference between daytime and nighttime levels. We also studied 23 healthy adult
      females (20-24 years of age) on 24-hour-urine for the comparison of the reference
      values of newborn infants. Fifty metabolites of DHEA, pregnenolone, 17
      hydroxypregnenolone, androstenedione, progesterone, 17-hydroxyprogesterone, 21
      deoxycortisone, corticosterone, 18-hydroxycorticosterone, aldosterone, 18
      hydroxycortisol, 11-deoxycortisol, cortisone, cortisol, and estrogen in each
      infant were measurable without interference, but 13 metabolites of 11
      hydroxyandrostenedione, pregnenolone, 11-deoxycorticosterone, corticosterone, 11
      dehydrocorticosterone, 21-deoxycortisol, 11-deoxycortisol and cortisol were
      unmeasurable in each infant due to the interference of fetal cortex steroids as
      confirmed by abnormal peak area ratios of two mass ions. All 63 metabolites in
      each control adult were measurable without interference. 16alpha-, 16beta-, and
      15beta-hydroxy metabolites of 3beta-hydroxy-5-en-steroids, and 6beta-, 18-hydroxy
      and 11-oxo-metabolites of corticosteroids were significantly higher in full-term
      newborn infants than those in adults as previously reported. Urinary steroids
      showed little circadian variation in the newborn infants, indicating that spot
      urine can substitute for 24-hour urine.

PMID- 14709853
TI  - Acromegaly with fibrous dysplasia: McCune-Albright Syndrome -- clinical studies
      in 3 cases and brief review of literature--.
AB  - The McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic
      fibrous dysplasia, cafe-au-lait macules and hyperfunctioning endocrinopathies
      including growth hormone (GH) excess. Polyostotic bone lesions and cafe-au-lait
      macules are common while monostotic bone lesions are rare. Similarly, acromegaly
      as a manifestation of endocrine hyperfunction with MAS is uncommon and in most of
      the instances somatotropinoma has not been documented. We report 3 patients, two
      of them had monostotic lesion, none had cafe-au-lait macules and all had GH
      secreting pituitary macroadenoma. All of them underwent transfrontal pituitary
      adenomectomy and had histopathological confirmation of GH secreting pituitary
      adenoma. A brief review of literature is also presented.

PMID- 14709854
TI  - Immunization with ACE (Angiotensin Converting Enzyme) develops diabetic changes
      in the kidney and retina in diabetogenic rats.
AB  - In normal New Zealand white rabbits, immunization with rabbit lung ACE
      (angiotensin converting enzyme) induced atherosclerotic retinal changes, and
      glomerular changes similar to those seen in diabetic nephropathy. Also, in
      genetically diabetogenic rats, immunization with the rabbit lung ACE induced
      diabetic nephropathy and retinopathy.

PMID- 14709855
TI  - A case of a novel mutant vasopressin receptor-dependent nephrogenic diabetes
      insipidus with bilateral non-obstructive hydronephrosis in a middle aged man:
      differentiation from aquaporin-dependent nephrogenic diabetes insipidus by
      response of factor VII and von Willebrand factor to 1-diamino-8-arginine
      vasopressin administration.
AB  - We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent
      nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive
      hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2
      (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor
      (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old
      man was admitted to hospital because of polyuria, which had been present from
      infancy and was suspected of causing non-obstructive hydronephrosis. His mother's
      father, the older brother of his mother and his second daughter also all had
      polyuria. Sodium concentration, osmolality and vasopressin in blood were high,
      while sodium concentration and osmolality in urine were low. There were no
      changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion.
      Neither was heart rate, diastolic blood pressure nor facial flushing affected.
      These findings suggested this case was V2R-dependent NDI rather than AQP2
      dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R
      missense mutation involving a substitution of cysteine for arginine at position
      104 (R104C) located in the first extracellular loop of the V2R. It was also found
      that the patient's mother and his second daughter were heterozygous for this
      R104C mutation.

PMID- 14709856
TI  - The prevalence of late onset congenital adrenal hyperplasia in hirsute women from
      Central Anatolia.
AB  - Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association
      with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study
      aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute
      women. Sixty-three patients with hirsutism were evaluated to determine the
      frequency of LO CAH by comparing them with their age and body mass index matched
      28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20
      were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent
      ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11
      desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA
      S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and
      DHEA-S levels did not differ between groups. However, stimulated F levels were
      found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients
      with hirsutism met the criterion for 21 hydroxylase deficiency. We found no
      subject presumed to have 11-beta hydroxylase deficiency, but one subject in
      control group (3.57%) and two patients among PCOS subjects (4.65%) had
      exaggerated DHEA-S response which was suggestive of mild 3-beta hydroxysteroid
      dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems
      to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia.
      Mild 3-beta HSD deficiency may also be an underlying cause for hirsutism and it
      may be seen without any clinical presentation. Adrenal hyperactivity is likely to
      be the main reason of hyperandrogenemia in women with hirsutism.

PMID- 14709857
TI  - A case of anterior hypopituitarism showing recurrent pituitary mass associated
      with central diabetes insipidus.
AB  - We report a case of anterior hypopituitarism showing recurrent pituitary mass
      associated with central diabetes insipidus. A 76-year old woman was hospitalized
      with general fatigue and 5 kg body weight loss. Endocrinological examinations and
      pituitary provocative tests demonstrated hypopituitarism and central diabetes
      insipidus. T1-weighted image of magnetic resonance imaging (MRI) revealed an
      intrasellar cystic mass with ring enhancement suggesting pituitary abscess. MRI
      films subsequently obtained from another hospital and studied retrospectively
      showed intrasellar cystic mass with ring enhancement 4 years earlier, and a mass
      shape that was decreased after 2 years. Over the subsequent years, the patient
      has remained asymptomatic with hormone replacement therapy only. Cystic pituitary
      adenoma or Rathke's cleft cyst with repeated infection may be involved in the
      repeated change of pituitary mass shape although neither pituitary surgery nor a
      pituitary biopsy was performed because of the patient's age and condition. It is
      reported that apparent recurrence of Rathke's cleft cysts after initially
      successful surgery was higher than suggested by previous reports, and that long
      term follow-up with pituitary imaging and neuroophthalmological assessment is
      essential. Careful evaluation by follow-up brain MRI is needed in the present
      case to prevent future recurrence of pituitary abscess.

PMID- 14709858
TI  - Efficacy of immunoglobulin and prednisolone in diabetic amyotrophy.

PMID- 14709859
TI  - A significant adverse correlation between serum cortisol and TSH in a case of
      cyclic Cushing's disease based on a continuous three-year observation.

PMID- 14709860
TI  - A lethal complication, acute necrotizing pancreatitis, of Turner's Syndrome with
      primary hyperparathyroidism.

PMID- 14709861
TI  - Benign Thyroid Diseases among Chernobyl Liquidators.

PMID- 14709862
TI  - Recent developments in the maytansinoid antitumor agents.
AB  - Maytansine and its congeners have been isolated from higher plants, mosses and
      from an Actinomycete, Actinosynnema pretiosum. Many of these compounds are
      antitumor agents of extraordinary potency, yet phase II clinical trials with
      maytansine proved disappointing. The chemistry and biology of maytansinoids has
      been reviewed repeatedly in the late 1970s and early 1980s; the present review
      covers new developments in this field during the last two decades. These include
      the use of maytansinoids as "warheads" in tumor-specific antibodies, preliminary
      metabolism studies, investigations of their biosynthesis at the biochemical and
      genetic level, and ecological issues related to the occurrence of such typical
      microbial metabolites in higher plants.

PMID- 14709863
TI  - Cerebrosides and a monoacylmonogalactosylglycerol from Clinacanthus nutans.
AB  - A mixture of nine cerebrosides and a monoacylmonogalactosylglycerol were
      separated from the leaves of Clinacanthus nutans. The structures of the
      cerebrosides were characterized as 1-O-beta-D-glucosides of phytosphingosines,
      which comprised a common long-chain base, (2S,3S,4R,8Z)-2-amino-8(Z)-octadecene
      1,3,4-triol with nine 2-hydroxy fatty acids of varying chain lengths (C(16),
      C(18), C(20-26)) linked to the amino group. The glycosylglyceride was
      characterized as (2S)-1-O-linolenoyl-3-O-beta-D-galactopyranosylglycerol. The
      structures were established on the basis of the spectroscopic data and chemical
      reactions.

PMID- 14709864
TI  - Potentiometric and spectroscopic studies on yttrium(III) complexes of
      dihydroxybenzoic acids.
AB  - The equilibrium reactions of yttrium(III) ion with dihydroxybenzoic acids (2,3
      dihydroxybenzoic acid (2,3-DHBA) and 3,4-dihydroxybenzoic acid (3,4-DHBA))
      (H(3)L) were investigated in aqueous solution by means of potentiometric and
      spectroscopic methods, in 0.1 mol.l(-1) ionic strength medium at 25 degrees C.
      The stability constants are reported for YL, YL(HL)(2-) and YL(2)(3-)- type
      mononuclear complexes. 2,3-DHBA can bind Y(III) ion strongly and the salicylate
      mode is effective over the acidic pH range. But in higher pH range, 2,3-DHBA and
      3,4-DHBA act more efficiently through catecholate groups. The complexes of 2,3
      DHBA are more stable than the complexes of 3,4-DHBA.

PMID- 14709865
TI  - Indirect potentiometric titration of ascorbic acid in pharmaceutical preparations
      using copper based mercury film electrode.
AB  - A simple and rapid potentiometric method for the estimation of ascorbic acid in
      pharmaceutical dosage forms has been developed. The method is based on treating
      ascorbic acid with iodine and titration of the iodide produced equivalent to
      ascorbic acid with silver nitrate using Copper Based Mercury Film Electrode
      (CBMFE) as an indicator electrode. Interference study was carried to check
      possible interference of usual excipients and other vitamins. The precision and
      accuracy of the method was assessed by the application of lack-of-fit test and
      other statistical methods. The results of the proposed method and British
      Pharmacopoeia method were compared using F and t-statistical tests of
      significance.

PMID- 14709866
TI  - HPLC retention behavior of poly-aromatic-hydrocarbons on aminopropyl silica gels
      modified with Cu(II)- and Ni(II)-phthalocyanine derivatives in non-polar eluent.
AB  - A comparative study was conducted to elucidate the mechanism underlying the
      separation of poly-aromatic-hydrocarbons (PAHs) and related compounds thereof on
      a column packed with silica gels modified with Ni(II)- or Cu(II)-phthalocyanine
      derivatives (PCS) (Ni- or Cu-PCS(D) column) and commercially available PYE and
      NPE columns with a non-polar eluent, such as n-hexane. It has been revealed that
      the dominant interaction responsible to the separation of PAHs on the Cu-PCS(D)
      and the PYE columns with n-hexane is the pi-pi interaction; however, in the
      separation of PAHs having 4 rings such as pyrene on the Ni-PCS(D) column,
      participation of pi-d interaction was indicated. The predominant role of pi-pi
      interaction in the separation of PAHs of less than three rings on the Ni-PCS(D)
      column was demonstrated using anthracene. All the columns possessed planar
      recognition ability and were estimated to be potentially useful in the separation
      and the analysis of PAHs.

PMID- 14709867
TI  - Structures of platinum(II) complexes of 2-aminomethylaziridine and S-2
      aminomethylazetidine and correlation of anticancer activities of (2
      aminomethylazacycloalkane)platinum(II) complexes with the geometry of the chelate
      rings formed with platinum(II).
AB  - The spectroscopic properties of platinum(II) complexes with 2-aminomethyl
      derivatives of small-membered 1-aza-cycloalkane, i.e., =2
      aminomethylaziridine=azida and S-2-aminomethylazetidine=S-azeda, and the crystal
      structures of their dichloro complexes demonstrate that the conformation of the
      fused three- (azida) or four- (S-azeda) and five-membered chelate ring formed by
      the coordination of S-azida and S-azeda to platinum(II) has an S(N) absolute
      configuration at the secondary amine site and that the two alkyl groups extend
      axially from the five-membered chelate ring. The chelate ring of the azida is
      more planar than the S-azeda or other 2-aminomethyl-1-azacycloalkanes. The
      anticancer activity reported for azeda and 2-aminomethylpyrrolidine appears to be
      related to their coordination structure, namely the presence of cis-fused
      successive rings.

PMID- 14709868
TI  - Preparation and characterization of novel branched beta-cyclodextrins having beta
      D-galactose residues on the non-reducing terminal of the side chains and their
      specific interactions with peanut (Arachis hypogaea) agglutinin.
AB  - Six novel branched beta-cyclodextrins (betaCDs) having beta-D-galactose residues
      on the non-reducing terminal of the sugar side chains, namely 6(1),6(4)-di-O
      (beta-D-galactosyl)-betaCD (10), 6-O-(beta-D-galactosyl)-betaCD (11), 6(1),6(4)
      di-O-(beta-lactosyl)-betaCD (14), 6-O-(beta-lactosyl)-betaCD (15), 6(1),6(4)-di-O
      (4'-O-beta-D-galactosyl-beta-lactosyl)-betaCD (18), and 6-O-(4'-O-beta-D
      galactosyl-beta-lactosyl)-betaCD (19), were chemically synthesized using the
      trichloroacetimidate method. The reaction products were separated by HPLC on an
      amino column into dibranched and monobranched betaCDs. Their structures were
      confirmed by mass spectrometry (MS) and two-dimensional (2D) NMR spectroscopic
      analysis. To study the length of the sugar side chains attached to the CD ring,
      which leads to differences in the functions of the branched CDs, interactions of
      these compounds with peanut (Arachis hypogaea) agglutinin (PNA) were investigated
      using an optical biosensor and an inhibition assay based on hemagglutination. The
      results showed that all branched betaCDs interacted with PNA, and the binding
      affinity was 18>14>10 and 19>15>11 when the derivatives were compared on the
      basis of side chain length.

PMID- 14709869
TI  - Studies on tellurium-containing heterocycles. Part 20. Reactions of 2
      benzoselenopyrylium salts and 2-benzotelluropyrylium salts with nucleophiles:
      formation of 1-functionalized 1H-isoselenochromenes and 1H-isotellurochromenes.
AB  - The reactions of the 2-benzoselenopyrylium (1A) and 2-benzotelluropyrylium
      cations (1B) with a variety of nucleophiles have been investigated. LiAlH(4),
      sodium alkoxide (NaOMe, NaOi-Pr and NaOt-Bu), diethylamine, n-butylamine and
      acetone reacted with 1 to give the 1H-isochromenes (2) and the corresponding 1
      substituted products (4-9) under mild conditions in almost good to high yields.
      The 1-alkyl(phenyl)isoselenochromenes (10-13) and 1-benzylisochromenes (18A,
      18B), which were produced by the reaction of the salts 1 with Grignard reagents,
      were converted to the corresponding 1,3-disubstituted 2-benzopyrylium salts (14
      17, 19) by treatment with triphenylcarbenium tetrafluoroborate (Ph(3)C(+) BF(4)(
      )), respectively. The 1-benzylselenopyrylium salts (19A) and 1
      benzyltelluropyrylium salts (19B) exist in the solvent as an equilibrium mixture
      of the salts (19) and the corresponding (Z)-benzylidene compounds (20).

PMID- 14709870
TI  - CCR5 antagonists as anti-HIV-1 agents. 1. Synthesis and biological evaluation of
      5-oxopyrrolidine-3-carboxamide derivatives.
AB  - A novel lead compound, N-(3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl)-1-methyl-5
      oxo-N-phenylpyrrolidine-3-carboxamide (1), was identified as a CCR5 antagonist by
      high-throughput screening using [(125)I]RANTES and CCR5-expressing CHO cells. The
      IC(50) value of 1 was 1.9 microM. In an effort to improve the binding affinity of
      1, a series of 5-oxopyrrolidine-3-carboxamides was synthesized. Introduction of
      3,4-dichloro substituents to the central phenyl ring (10i, IC(50)=0.057 microM;
      11b, IC(50)=0.050 microM) or replacing the 1-methyl group of the 5-oxopyrrolidine
      moiety with a 1-benzyl group (12e, IC(50)=0.038 microM) was found to be effective
      for improving CCR5 affinity. Compound 10i, 11b, and 12e also inhibited CCR5-using
      HIV-1 envelope-mediated membrane fusion with IC(50) values of 0.44, 0.19, and
      0.49 microM, respectively.

PMID- 14709871
TI  - Stannyl radical addition-cyclization of oxime ethers connected with olefins.
AB  - Stannyl radical addition-cyclization of oxime ethers connected with olefin
      moieties was studied. The radical reactions proceeded effectively by the use of
      triethylborane as a radical initiator to provide the functionalized pyrrolidines
      via a carbon-carbon bond-forming process.

PMID- 14709872
TI  - A new series of estrogen receptor modulators: effect of alkyl substituents on
      receptor-binding affinity.
AB  - New types of selective estrogen receptor modulators (SERMs) were synthesized and
      evaluated for their binding affinity and biological effect on reproductive cells.
      A proposed lead structure (B) was derivatized to provide compounds 30 and 44,
      which showed good estrogen-receptor binding affinity (K(i) values: 6.3 and 10 nM,
      respectively), as well as minimal impact on mammary and uterine carcinoma cells.
      Introduction of an alkyl group in the core structure considerably enhanced
      receptor-binding affinity of the compounds tested. Synthesis and structure
      activity relationships of these compounds are described.

PMID- 14709873
TI  - Mechanistic considerations for the consecutive cyclization of 2,3
      dibromopropylamine hydrobromide giving a strained molecule, 1
      azabicyclo[1.1.0]butane.
AB  - The effective formation of 1-azabicyclo[1.1.0]butane (2) by treatment of 2,3
      dibromopropylamine hydrobromide (1) with n-BuLi could be understood considering a
      rational reaction pathway via both transition states 10 and 19 based on the
      intramolecular Br...Li(+) coordination. A similar cyclization pathway starting
      from N-benzyl-3-bromopropylamine hydrochloride (17) to afford N-benzylazetidine
      (18) could also be postulated on the basis of a transition state 20 involving the
      intramolecular Br...Li(+) coordination.

PMID- 14709874
TI  - Stereochemistry of the asymmetric carbopalladation of allenes followed by
      nucleophilic substitution reactions with carbo- and aminonucleophiles.
AB  - The stereochemistry of the asymmetric palladium-catalyzed reaction of allenes
      with iodobenzene followed by nucleophilic substitution reaction with sodium
      malonate and N-methylbenzylamine is described. On the basis of the absolute
      configuration of the product and the stereochemical result of a similar reaction
      of a chiral allene, the mechanism of the above asymmetric reactions is discussed.

PMID- 14709875
TI  - Seven novel seco-prezizaane-type sesquiterpenes from the pericarps of Illicium
      merrillianum.
AB  - Seven new seco-prezizaane-type sesquiterpenes were isolated from the methanol
      extract of the pericarps of Illicium merrillianum. Their structures were
      elucidated as 3-deoxypseudoanisatin (1), 2beta-hydroxy-3,6-dedioxypseudoanisatin
      (2), 8alpha-hydroxy-10-deoxycyclomerrillianolide (3), 10beta
      hydroxypseudoanisatin (4), 10beta-hydroxycyclopseudoanisatin (5), 1,6-dihydroxy-3
      deoxyminwanensin (6), and 8-deoxymerrilliortholactone (7) by analyses of their
      spectroscopic data and chemical transformation. Compounds 4 and 5 as well as 6
      and 7 coexist as a keto/acetal equilibrated mixture in methanol solution.

PMID- 14709876
TI  - Two new cytotoxic clerodane diterpenoids from Casearia membranacea.
AB  - In addition to casearlucin A (3), two new clerodane diterpenes, caseamembrols A
      (1) and B (2) have been isolated from the leaves and twigs of Casearia
      membranacea by bioassay-guided fractionation. The structures of the new compounds
      were established on the basis of extensive 1D- and 2D-NMR spectroscopic analysis.
      Compounds 1-3 exhibited significant cytotoxicity against human prostate (PC-3)
      cancer cells.

PMID- 14709877
TI  - Stereodivergent synthesis of chiral 2-alkenylaziridines: palladium(0)-catalyzed
      2,3-cis-selective aziridination and base-mediated 2,3-trans-selective
      aziridination.
AB  - Whereas treatment of the allylic mesylates of N-protected 2-alkyl-4-amino-(E)-2
      alken-1-ols with sodium hydride in DMF yields exclusively the corresponding
      thermodynamically less stable 2,3-trans-2-alkenyl-3-alkylaziridines, exposure of
      the methyl carbonates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols to a
      catalytic amount of Pd(PPh(3))(4) in THF or 1,4-dioxane affords predominantly the
      corresponding thermodynamically more stable 2,3-cis-2-alkenyl-3-alkylaziridines.
      The kinetically favored trans-selective aziridination would be attributed to the
      allylic 1,3-strain in aza-anionic intermediates. The conformational analysis of
      the sterically highly congested 2-alkenylaziridines thus obtained is also
      presented.

PMID- 14709878
TI  - Studies on non-thiazolidinedione antidiabetic agents. 3. Preparation and
      biological activity of the metabolites of TAK-559.
AB  - Preparation and biological activity of the metabolites of the potent
      antihyperglycemic and antihyperlipidemic agent, (E)-4-(4-[(5-methyl-2-phenyl-1,3
      oxazol-4-yl)methoxy]benzyloxyimino)-4-phenylbutyric acid (TAK-559) (1), were
      investigated. Metabolites M-I (2), M-II (3), M-III (4) and M-IV (5) were
      synthesized and their biological activities were evaluated by in vitro and in
      vivo experiments. Compounds 2-4 activate human peroxisome proliferator-activated
      receptor gamma one (hPPARgamma1) and hPPARalpha, but their activities are weaker
      than those of TAK-559 (1). Compound 5 only activates hPPARgamma1 weakly. TAK-559
      (1) showed potent in vivo plasma glucose and triglyceride lowering activities in
      Wistar fatty rats after intraperitoneal administration, while its metabolites (2
      5) showed comparatively weak activities.

PMID- 14709879
TI  - Chiral ligand-controlled asymmetric conjugate addition of alpha
      trimethylsilanylacetate to acyclic and cyclic enones.
AB  - The reaction of lithium ester enolate with enones provides a challenge for
      chemoselectivity, that is, discrimination between a conjugate addition and a 1,2
      addition. Asymmetric conjugate addition of a lithium enolate of alpha
      trimethylsilanylacetate to acyclic and cyclic alpha,beta-unsaturated ketones was
      mediated by an external chiral ligand to give the corresponding 1,4-adducts in
      good enantioselectivity of 74% and good chemoselectivity.

PMID- 14709880
TI  - Justicidone, a novel p-quinone-lignan derivative from Justicia hyssopifolia.
AB  - An uncommon, previously unreported p-quinone-lignan compound called justicidone
      (4-(1,3-benzodioxol-5-yl)-6-methoxynaphtho[2,3-c]furan-1,5,8(3H)-trione) (2),
      along with the known savinin (1) were isolated from Justicia hyssopifolia
      (Acanthaceae). Their structures were determined by spectroscopic methods.

PMID- 14709881
TI  - An improved synthesis of benzocycloalkanone derivatives.
AB  - A convenient and improved annulation method for the synthesis of bicyclic ketones
      was developed. A 2,2-dimethyl-6-(2-phenylsulfonyl)ethylcyclohexanone was
      converted into a sulfonylester by the addition of ethyl acetate and subsequent
      dehydration. A Dieckmann type condensation of the sulfonylester followed by
      desulfonylation afforded the 8,8-dimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-2
      one in good yield. This annulation method was also applicable for the synthesis
      of the benzocyclooctanone derivative.

PMID- 14709882
TI  - Immunosuppressive diterpenes from Veronicastrum sibiricum.
AB  - Two new diterpenes, named sibiriquinone A (1) and B (2), along with four known
      diterpenes have been isolated from the aerial part of Veronicastrum sibiricum.
      Their structures were elucidated by spectroscopy. The isolated compounds showed
      significant immunosuppressive activities.

PMID- 14709883
TI  - Cytotoxic C-benzylated dihydrochalcones from Uvaria acuminata.
AB  - Two new C-benzylated dihydrochalcones, isochamuvaritin (1) and acumitin (2), have
      been isolated from the African medicinal plant Uvaria acuminata, together with
      the previously reported benzylbenzoate (3), uvaretin (4), isouvaretin (5),
      diuvaretin (6), and uvangoletin (7). The structural elucidation of compounds 1
      and 2 in spectroscopic studies is described. C-Benzylated dihydrochalcones,
      especially 1, 2, 4, and 6, showed considerable cytotoxicity toward human
      promyelocytic leukemia HL-60 cells.

PMID- 14709884
TI  - Pregnane- and furostane-type oligoglycosides from the seeds of Allium tuberosum.
AB  - Two furostane-type steroidal oligoglycosides (1, 2), together with a new pregnane
      type oligoglycoside (3), were obtained from the seeds of Allium tuberosum
      ROTTLER. On the basis of spectroscopic analysis, the structures of three new
      oligoglycosides (1-3) were elucidated as 26-O-beta-D-glucopyranosyl-(25R)
      3beta,22xi,26-trihydroxyl-5alpha-furostane 3-O-beta-chacotrioside, 26-O-beta-D
      glucopyranosyl-(25S)-3beta,5beta,6alpha,22xi,26-pentahydroxyl-5beta-furostane 3-O
      alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside, and 3-O-alpha-L
      rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl 3beta,5beta,6alpha,16beta
      tetrahydroxypregnane 16-(5-O-beta-D-glucopyranoyl-4(S)-methyl-5-hydroxypentanoic
      acid) ester, respectively.

PMID- 14709885
TI  - Selective scavenging property of the indole moiety for the nitrating species of
      peroxynitrite.
AB  - The inhibitory effect on tyrosine nitration and oxidation of peroxynitrite was
      evaluated for more than 40 reagents including natural and synthetic compounds,
      and the inhibiting efficiency of each compound for nitration was compared with
      that for oxidation, to characterize its property as a peroxynitrite scavenger. In
      the presence of various concentrations of testing compounds, the nitrating and
      oxidizing activities were measured by monitoring the formation of 3-nitrotyrosine
      and dityrosine with an HPLC-UV-fluorescence detector. The IC(50) values for
      nitration and oxidation were determined, and the ratio of these two IC(50) values
      was calculated for each compound. Although the IC(50) values varied from compound
      to compound, it was revealed that the ratio of two IC(50) values (IC(50) for
      oxidation/IC(50) for nitration) was 1 in almost all the compounds tested, except
      five indole derivatives (L-tryptophan, melatonin, 5-methoxytryptamine,
      tryptamine, and tetrahydro-beta-carboline) and one synthetic selenium-containing
      compound ((2R,3R,4S)-2-amino-3,4-dihydroxy-5-phenylselenopentan-1-ol, ADPP). The
      indole derivatives showed a specific inhibitory effect on tyrosine nitration
      without affecting the oxidation. ADPP was confirmed to have a preferable
      inhibitory activity for tyrosine oxidation. It was suggested that compounds
      showing an IC(50) value ratio of 1 scavenged the common species for nitration and
      oxidation, while the indole derivatives and ADPP preferably scavenged the
      nitrating and oxidizing species, respectively. From a stopped flow study, it was
      also revealed that the nitrotyrosine formation was relatively slow, unlike an OH
      radical reaction. These results imply that the peroxynirite reaction at least
      partly proceeds through specific species for nitration.

PMID- 14709886
TI  - Determination of alpha-tocopherol in the Traditional Chinese Medicinal
      preparation Sea buckthorn oil capsule by non-aqueous reversed phase-HPLC.
AB  - A non-aqueous reversed phase HPLC was developed for determining alpha-tocopherol
      in Sea buckthorn oil capsule without the need for saponification. A reversed
      phase column (Alltima C(18), 4.6 x 250 mm, 5 microm) was used with a mobile phase
      of methanol-acetonitrile (95 : 5, v/v) and flow rate of 1 ml/min. The contents in
      capsule were extracted with n-hexane. Detection wavelength was set at 292 nm.
      Each analysis requires no longer than 20 min. The linearity range for alpha
      tocopherol was 9.4-47.0 microg/ml. The detection limit was 0.94 microg/ml. The
      mean recovery was 95.82 (RSD 2.3%). This method is suitable for quantitative
      analysis of alpha-tocopherol in Sea buckthorn oil or its Traditional Chinese
      Medicinal preparation.

PMID- 14709887
TI  - 3-epicabraleahydroxylactone and other triterpenoids from camellia oil and their
      inhibitory effects on Epstein-Barr virus activation.
AB  - The structure of a triterpenoid isolated from the nonsaponifiable lipid (NSL) of
      the seed oil of the camellia (Camellia japonica L.; Theaceae) was established to
      be (20S)-3beta-hydroxy-25,26,27-trisnordammaran-24,20-olide (1; 3
      epicabraleahydroxylactone) on the basis of spectroscopic and chemical methods.
      Six other triterpenoids isolated from the NSL were identified as 3
      epicabraleadiol (2), ocotillol II (3), ocotillol I (4), dammarenediol II (5),
      (20R)-taraxastane-3beta,20-diol (6), and lupane-3beta,20-diol (7). Upon
      evaluation of the seven triterpenoids (1-7) with respect to their inhibitory
      effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells, three compounds (5-7) showed
      potent inhibitory effects against EBV-EA induction (IC(50) values of 277-420 mol
      ratio/32 pmol TPA).

PMID- 14709888
TI  - A new pentacyclic triterpenoid glucoside from Prunus serrulata var. spontanea.
AB  - A new triterpenoid, 2alpha,3alpha,24-trihydroxyurs-12-en-28-oic acid-28-O-beta-D
      glucopyranosyl ester (4) along with four known triterpenoids, ursolic acid (1),
      2alpha-hydroxyursolic acid (2), 2alpha,3alpha,24-trihydroxyurs-12-en-28-oic acid
      (3), and 2alpha,3alpha,19alpha,24-tetrahydroxyurs-12-en-28-oic acid-28-O-beta-D
      glucopyranosyl ester (5), were isolated from the leaves of Prunus serrulata var.
      spontanea (Rosaceae). Compounds 3-5 showed ONOO(-) scavenging activity, whereas
      compounds 1 and 2 were virtually inactive.

PMID- 14709889
TI  - Synthesis of hexahydropyridazine-3-phosphonic acid.
AB  - The synthesis of hexahydropyridazine-3-phosphonic acid (piperidazine-3-phosphonic
      acid) was performed via a hetero-Diels-Alder reaction followed by Lewis acid
      catalyzed phosphonylation. This two-step procedure was improved to a one-pot
      reaction.

PMID- 14709890
TI  - Synthesis and antifungal activity of novel 14-membered benzomacrolides, as
      galbonolide analogues.
AB  - Asymmetric total synthesis of benzene analogues of galbonolide, a 14-membered
      antifungal macrolide, possessing a benzene ring instead of a conjugated diene
      structure, was achieved starting from chiral 1-aryl-1-propanol obtained by enzyme
      catalyzed kinetic resolution with high enantioselectivity. Representatively, a
      method for the introduction of a methylthio and chloride function at the vinyl
      position was also established. The resulting analogues unfortunately exhibited
      very little antifungal potency in comparison with galbonolide A.

PMID- 14709891
TI  - Phagocytic removal of apoptotic spermatogenic cells by Sertoli cells: mechanisms
      and consequences.
AB  - More than half of differentiating spermatogenic cells undergo apoptosis before
      maturing into spermatozoa during mammalian spermatogenesis. These cells are
      selectively and rapidly eliminated through phagocytosis by Sertoli cells, a
      testicular somatic cell type possessing phagocytic activity. We have investigated
      the mechanism by which Sertoli cells specifically recognize and phagocytose
      apoptotic spermatogenic cells and the consequences of phagocytosis. We showed by
      in vitro as well as in vivo analyses that Sertoli cells recognize apoptotic
      spermatogenic cells through the binding of their surface receptor, class B
      scavenger receptor type I, to phosphatidylserine that is expressed on the surface
      of spermatogenic cells during apoptosis. The inhibition of phagocytosis in live
      animals resulted in a decrease in the number of epididymal sperm. These results
      suggest that phosphatidylserine-mediated phagocytosis of apoptotic spermatogenic
      cells by Sertoli cells is required for the efficient production of sperm.

PMID- 14709892
TI  - Effects of oxygen on the reactivity of nitrogen oxide species including
      peroxynitrite.
AB  - This paper describes the O(2)-dependent control of the reactivity of nitrogen
      oxide species for the production of biologically important nitrated and
      nitrosated compounds. In this study, the effects of O(2) on the reactivity of NO,
      NO(2), and ONOO(-)/ONOOH for nitration of tyrosine (Tyr) and nitrosation of
      glutathione (GSH) and morpholine (MOR) were examined. NO produced S
      nitrosoglutathione (GSNO) and N-nitrosomorpholine (NMOR) through the formation of
      N(2)O(3) under aerobic conditions, and NO(2) produced 3-nitrotyrosine (3
      NO(2)Tyr), GSNO, and NMOR. Transnitrosation from GSNO to MOR was observed only in
      the presence of O(2). Although preformed ONOO(-)/ONOOH produced all the products
      under aerobic conditions, the formation of 3-NO(2)Tyr and GSNO was markedly
      reduced and the formation of NMOR was enhanced under anaerobic conditions. The
      reactivity of the CO(2) adduct of ONOO(-) was similarly dependent on O(2). 3
      NO(2)Tyr was produced effectively by reaction with ONOO(-)/ONOOH at the O(2)
      concentration of 270 microM and by reaction with its CO(2) adduct at O(2)
      concentrations greater than 5 microM. Generation of.OH from ONOO(-)/ONOOH was
      suppressed under anaerobic conditions. The reactivity of ONOO(-)/ONOOH and.OH
      generation from ONOO(-) were reversibly controlled by the O(2) concentration.

PMID- 14709893
TI  - Phorbol myristate acetate stimulates degradation of a structural analogue of
      platelet-activating factor to a neutral lipid in human leukemic K562 cells:
      relevance to the release of lipids.
AB  - In our attempt to investigate the mechanism of the release of platelet-activating
      factor (PAF) from cells, the erythroleukemic cell line K562 was preloaded with a
      radiolabeled PAF analogue having an ethylcarbamyl residue, 1-O-octadecyl-2-O
      ethylcarbamyl-sn-glycero-3-phosphocholine (ethylcarbamyl-PAF), that is resistant
      to the hydrolytic action of PAF acetylhydrolase. Its extracellular release was
      monitored using an albumin back-extraction method, and its metabolic degradation
      was analyzed by TLC. Phorbol myristate acetate (PMA) was found to stimulate the
      release of two radioactive lipids, ethylcarbamyl-PAF itself and its metabolite, 1
      O-octadecyl-2-ethylcarbamyl-sn-glycerol, whereas only ethylcarbamyl-PAF was
      released from the resting cells. The increased release of radioactive lipids in
      PMA-stimulated cells was suggested to be due to stimulated degradation of
      intracellular ethylcarbamyl-PAF into the cell-permeable metabolite. Thus K562
      cells have much less capacity to release intact PAF-like lipid in comparison with
      its high ability to uptake exogenously added PAF analogues previously described
      by us and others.

PMID- 14709894
TI  - The immune-enhancing effect of the herbal combination Bouum-Myunyuk-Dan.
AB  - The herbal formulation Bouum-Myunyuk-Dan (BMD) has long been used for various
      diseases. It has been shown to have antimicrobial and anti viral activity
      clinically. However, it is still unclear how BMD exerts these effects in
      experimental models. In this study, we investigated the effect of BMD on the
      production of cytokines in a human T cell line, MOLT-4 cells, and in mouse
      peritoneal macrophages. As a result, BMD significantly increased the viability
      and proliferation of splenocytes (p<0.05) and also significantly increased
      interleukin (IL)-2 and IL-4 production compared with media control (about 2.7
      fold for IL-2 and 6.7-fold for IL-4, p<0.05) after 24 h. BMD increased the
      interferon (IFN)-gamma production by 3.7-fold but there were no significant
      differences compared with controls. Maximal effective concentrations of BMD were
      1 mg/ml for IL-2 and IL-4 and 0.1 mg/ml for IFN-gamma. In addition, BMD (0.01
      mg/ml) increased the production of tumor necrosis factor (TNF)-alpha and IL-12 in
      mouse peritoneal macrophages (by 2.7-fold for TNF-alpha and 42.5-fold for IL-12,
      p<0.05). In conclusion, these data indicate that BMD may have an immune-enhancing
      effect through the production of various cytokines.

PMID- 14709895
TI  - The Oriental medicine "Cool-Cool (Cool-X-A)" inhibits inflammatory cytokine
      production and migration in mast cells.
AB  - Plant medications have been applied to treat pains from various types of
      arthritis in Korea. Rheumatoid arthritis (RA) is well known to be a chronic
      autoimmune/inflammatory disease that leads to progressive joint damage and
      cartilage destruction. Accumulation and activation of mast cells have been
      demonstrated in rheumatoid synovial tissue. Because infiltrated mast cells and
      their mediators may contribute to the initiation and progression of the
      inflammatory process and matrix degradation of RA, we tested the inhibitory
      effects of "Cool-Cool" (CC, Cool-X-A), an Oriental medication, on the production
      and migration of major inflammatory cytokines in mast cells. CC was treated in
      vitro before activation of human mast cell line (HMC-1) with phorbol 12-myristate
      13-acetate, and the cytotoxicity of CC was assessed by 3-[4,5-dimethylthiazol-2
      yl]-2,5-diphenyltetrazoliumbromide assay. CC had no cytotoxic effects on HMC-1
      cell viability. The inhibitory effects on cytokine production were monitored by
      enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain
      reaction (RT-PCR). CC inhibited not only the secretion but also the expression of
      TNF-alpha and IL-8 in HMC-1 cells. CC also suppressed migration of mast cells
      induced by stem cell factor. These findings may help in understanding the
      mechanism of action of this herbal medication, leading to the control of mast
      cells in inflammatory conditions like RA.

PMID- 14709896
TI  - Antioxidant and free radical-scavenging activity of Choto-san and its related
      constituents.
AB  - The antioxidant properties of Choto-san and its related constituents such as
      Chotoko and Choto-san without Chotoko, and phenolic compounds contained in
      Chotoko such as epicatechin, caffeic, acid and quercetin were evaluated. In the
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay, the scavenging
      activity of Chotoko (IC(50) 14.3 microg/ml) was found to be higher than that of
      Choto-san (IC(50) 206.2 microg/ml) and Choto-san without Chotoko (IC(50) 244.3
      microg/ml). Epicatechin (IC(50) 10.4 microM), caffeic acid (IC(50) 13.8 microM),
      and quercetin (IC(50) 7.1 microM) also revealed scavenging activity against DPPH
      radicals. Choto-san (IC(50) 67.7 microg/ml) exhibited stronger inhibitory
      activity against superoxide anion formation than Choto-san without Chotoko
      (IC(50) 92.4 microg/ml) but weaker activity than Chotoko (IC(50) 18.3 microg/ml).
      The generation of superoxide anion was also inhibited by epicatechin (IC(50)
      175.2 microM), caffeic acid (IC(50) 141.7 microM), and quercetin (IC(50) 18.7
      microM). In a hydroxyl radical-scavenging experiment, Choto-san (IC(50) 2.4
      mg/ml), Chotoko (IC(50) 2.2 mg/ml), Choto-san without Chotoko (IC(50) 2.8 mg/ml),
      epicatechin (IC(50) 3.9 mM), caffeic acid (IC(50) 3.6 mM), and quercetin (IC(50)
      1.9 mM) exhibited activity. In NG108-15 cells, when added simultaneously with
      H(2)O(2) (500 microM), Choto-san (250 microg/ml), Chotoko (250 microg/ml), Choto
      san without Chotoko (500 microg/ml), epicatechin (200 microM), caffeic acid (200
      microM), and quercetin (200 microM) effectively protected cells from oxidative
      damage. In conclusion, the present results provide evidence that Choto-san acts
      as an antioxidant and cytoprotective agent against oxidative damage, which is due
      at least partly to the phenolic compounds contained in Chotoko.

PMID- 14709897
TI  - Effects of low molecular weight chondroitin sulfate on type II collagen-induced
      arthritis in DBA/1J mice.
AB  - In order to evaluate the improvement in the treatment of chronic arthritis, we
      investigated chondroitin sulfate depolymerization product (low molecular weight
      chondroitin sulfate, LMWCS) and intact chondroitin sulfate (CS) in vitro and in
      vivo. LMWCS was prepared by a chemical depolymerization process induced by
      hydrogen peroxide in the presence of copper salts. LMWCS (300 mg/kg) and CS (1200
      mg/kg) were orally administered to DBA/1J mice once daily for 14 d prior to
      initial immunization with type II collagen. Their elastase activities and the
      production of cytokines in sera were examined on type II collagen-induced
      arthritis in DBA/1J mice. We also compared the paracellular transport of LMWCS
      and CS across Caco-2 cell monolayers and examined the inhibitory effects on
      elastase activities. LMWCS inhibited elastase activity slightly, but CS did not
      show inhibition. Hind paw edema was significantly decreased by LMWCS treatment.
      Levels of anti-type II collagen antibody and tumor necrosis factor-alpha (TNF
      alpha) in sera were also reduced by LMWCS treatment but not in case of CS,
      although no significant difference was observed between LMWCS and CS on
      interleukin-6 (IL-6) induction. The LMWCS preparation showed preventive effects
      on the type II collagen-induced arthritis in DBA/1J mice and better permeability
      through Caco-2 cells.

PMID- 14709898
TI  - Effect of sodium diclofenac on serum and tissue concentration of amoxicillin and
      on staphylococcal infection.
AB  - The effect of sodium diclofenac on serum and tissue amoxicillin concentration as
      well as their effect against staphylococcal infection was observed. Four
      polyurethane sponges were placed in the back of thirty rats. After 14 d, two
      granulomatous tissues received 0.5 ml of 10(8) cfu/ml (Staphylococcus aureus).
      Two days later, the rats were divided into five groups: group 1 received
      amoxicillin 50 mg/kg/p.o., group 2 received amoxicillin 25 mg/kg/p.o., group 3
      received sodium diclofenac 2.5 mg/kg/i.m. and amoxicillin 50 mg/kg/p.o., group 4
      received sodium diclofenac 2.5 mg/kg/i.m., and group 5 (control group) received
      NaCl 1 ml/p.o. After six hours of drug administration, blood serum (10 microl)
      and noninfected granulomatous tissues were placed on Mueller-Hinton agar
      inoculated with 10(8) cfu/ml (S. aureus). Infected tissues were dispersed in a
      sonic system and were spread (10 microl) on salt mannitol agar. Microorganisms
      were counted and the inhibition zones were measured after 18 h of incubation at
      37 degrees C. Amoxicillin tissue concentration was 6.27 microg/g for group 1,
      2.18 microg/g for group 2, and 0.72 microg/g for group 3. The serum
      concentrations were 11.56 microg/ml for group 1, 5.36 microg/ml for group 2, and
      1.34 microg/ml for group 3. No differences were observed among group 1, 2, and 3
      regarding staphylococci counts (Kruskall-Wallis test p>0.05). Group 4 reduced
      (p<0.05) staphylococci counts comparing to group 5. It was concluded that sodium
      diclofenac reduced serum and tissue amoxicillin concentration and, even in large
      doses, amoxicillin was not effective in eradicating the staphylococcal infection
      after 6 h of administration.

PMID- 14709899
TI  - Cytochrome P450 1A1 (CYP1A1) inhibitor alpha-naphthoflavone interferes with UDP
      glucuronosyltransferase (UGT) activity in intact but not in permeabilized hepatic
      microsomes from 3-methylcholanthrene-treated rats: possible involvement of UGT
      P450 interactions.
AB  - The effects of cytochrome P450 (P450, CYP) ligands and permeabilization of
      microsomes on 3-hydroxybenzo(a)pyrene [3-OH-B(a)P] glucuronidation mediated by
      rat hepatic microsomes were studied. While the UDP-glucuronosyltransferase (UGT)
      activity with non-permeabilized microsomes from 3-methylcholanthrene (MC)-treated
      rats was markedly reduced by alpha-naphthoflavone (NF), this inhibitor had hardly
      any effect when permeabilized microsomes were used in which the inhibitor was
      expected to have easy access to UGT. Kinetic analysis indicated that the
      inhibitory effect of alpha-NF is competitive. These results suggest that a UGT
      isoform(s) involved in 3-OH-B(a)P glucuronidation is interfered by a CYP1A
      inhibitor via a mechanism dependent on the intact nature of microsomal membranes
      in MC-treated rats. It is likely that P450 functions as a substrate transporter
      for some isoforms of UGT via possible interactions between UGT and P450.

PMID- 14709900
TI  - A study on the interaction between p60 c-Src receptor tyrosine kinase and
      arylcarboxylic and arylacetic acid derivatives based on docking modes and in
      vitro activity.
AB  - The fundamental role that receptor tyrosine kinases play in cancer and other
      proliferative diseases has provided the impetus for an extensive effort on the
      part of both academic and pharmaceutical laboratories to develop highly specific
      inhibitors. In this study, inhibitory activity of previously synthesized
      arylacetic and arylcarboxylic acid derivatives were examined against substrate of
      tyrosine kinase. It can be assumed that the activity of compounds becomes higher
      when the -CH(2) linkage exist between aromatic ring and the amide group of the
      side chain. In addition, when the R(1) and R(2) substitutents are methyl group in
      both series, the higher activity observed. The data obtained from docking study
      (DOCK4.0) indicated that compounds 2, 4, 7, 8, 11 render satisfactory interaction
      with the active site of enzyme, Lys295 of p60(c-Src) tyrosine kinase. Comparison
      of this interaction and the evaluation of biological data showed that compound 4
      is the most active among the entire derivatives.

PMID- 14709901
TI  - Development of an assay system for saikosaponin a using anti-saikosaponin a
      monoclonal antibodies.
AB  - For immunization, saikosaponin a (SSa) was conjugated with bovine serum albumin
      (BSA). The hapten number in an antigen conjugate was determined to be eleven by
      matrix-assisted laser adsorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF Mass). Hybridomas secreting monoclonal antibodies (MAb) against SSa
      were produced by fusing splenocytes immunized with SSa-BSA conjugate and a
      hypoxanthine-aminopterin-thymidine-sensitive (HAT) mouse myeloma cell line, P3
      X63-Ag8-653. A high specific MAb against SSa was selected from hybridomas using
      enzyme-linked immunosorbent assay (ELISA) analysis. Weak cross-reactivities
      occurred with saikosaponin c, b(2) and d, which are stereochemical and/or
      functional isomers of SSa, but no cross-reactivities were observed with other
      related steroidal glycosides. The full range of the assay extends 26 ng/ml to 1.5
      microg/ml of SSa. Good correlation of SSa concentrations in a crude extract of
      Bupleuri radix between ELISA and HPLC methods was obtained after hydrolysis of
      acyl saikosaponins by treatment with a mild alkaline solution. The newly
      established ELISA has been applied for the quantitative assay of SSa in the
      Bupleuri radix and the Kampo medicines (TCM) prescribed with Bupleuri radix.

PMID- 14709902
TI  - The flavonoid naringenin inhibits dimethylnitrosamine-induced liver damage in
      rats.
AB  - Naringenin, a phytoalexin found in grapefruits and tomatoes, has been reported to
      exhibit a wide range of pharmacological properties. In this study, we
      investigated the protective effect of naringenin on hepatic injury induced by
      dimethylnitrosamine (DMN) in rats. Oral administration of naringenin (20 and 50
      mg/kg daily for 4 weeks) remarkably prevented the DMN-induced loss in body and
      liver weights and inhibited the elevation of serum alanine transaminase,
      aspartate transaminase, alkaline phosphatase, and bilirubin levels. Naringenin
      also restored serum albumin and total protein levels, and reduced the hepatic
      level of malondialdehyde. Furthermore, DMN-induced collagen accumulation, as
      estimated by histological analysis of liver tissue stained with Sirius red, was
      reduced in the naringenin-treated rats. A reduction in hepatic stellate cell
      activation, as assessed by alpha-smooth muscle actin staining, was associated
      with naringenin treatment. In conclusion, these results demonstrate that
      naringenin exhibited in vivo hepatoprotective and anti-fibrogenic effects against
      DMN-induced liver injury. It suggests that naringenin may be useful in preventing
      the development of hepatic fibrosis.

PMID- 14709903
TI  - Studies on intestinal absorption of sulpiride (3): intestinal absorption of
      sulpiride in rats.
AB  - The aim of this study was to investigate whether the concomitant administration
      of the substrates or inhibitors of PEPT1, OCTN1, OCTN2, and P-glycoprotein
      affects the intestinal absorption of sulpiride in rats. The absorption of
      sulpiride from rat intestine was decreased by the substrates or inhibitors of
      PEPT1, OCTN1, and OCTN2. On the other hand, the absorption was increased by the
      substrates of P-glycoprotein. The effects of these concomitantly administered
      drugs on the pharmacokinetic behavior of sulpiride after oral administration in
      rats were investigated. Peak concentration (C(max)) and area under the plasma
      concentration-time curve (AUC(0-8 h)) of sulpiride were decreased by the
      concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, and
      OCTN2. However, the same parameters were significantly increased by the
      concomitant administration of the substrates of P-glycoprotein. The present
      results suggest the possibility of drug-drug interaction during the absorption
      process in the small intestine due to the coadministration of sulpiride and these
      agents. These findings provide important information for preventing adverse
      effects and for ensuring the effectiveness of sulpiride and concomitantly
      administered drugs.

PMID- 14709904
TI  - Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium
      tuberculosis strain Aoyama B, augments anti-tumor activities of X-ray irradiation
      against B16 melanoma in association with the improvement of type 1T cell
      responses.
AB  - In this study, the effects of combination therapy consisting of X-ray irradiation
      and Z-100 on the survival time of C57BL/6 mice inoculated with B16F10 melanoma
      were investigated. Survival time was significantly prolonged in B16F10 melanoma
      bearing mice treated with the X-ray irradiation (5 Gy) and Z-100 (10 mg/kg s.c.)
      combination therapy compared with mice irradiated with X-rays alone. The weight
      of primary tumors and number of metastatic colonies were also significantly
      suppressed by the combination therapy compared with that in the X-ray irradiation
      group. These results indicated that Z-100 could enhance the anti-tumor effects of
      radiotherapy against B16F10 melanoma. On the other hand, the survival time of CD4
      knockout mice bearing the same tumors was not prolonged by the combination
      therapy compared with mice irradiated with X-rays alone, suggesting that CD4+
      cells are partly involved in augmentation of the anti-tumor effect of
      radiotherapy by Z-100. In addition, type 1 cytokine (IL-2, IFN-gamma) production
      was significantly increased and type 2 cytokine (IL-4, IL-10) production was
      significantly suppressed in the tumor-bearing mice treated with the combination
      therapy compared with the X-ray irradiation group. Moreover, interleukin-12
      production by CD11c+ cells was also significantly increased in mice treated with
      the combination therapy compared with the X-ray irradiation group. These results
      indicate that Z-100 augmented the anti-tumor effects of X-ray irradiation.
      Moreover, we demonstrated that the effects of Z-100 were expressed at least in
      part, by the improvement of the T cell responses from type 2-dominant to type 1
      dominant via up-regulation of IL-12 production.

PMID- 14709905
TI  - Convenient procedures for human hair protein films and properties of alkaline
      phosphatase incorporated in the film.
AB  - We have developed a novel method of extracting proteins from human hair in the
      absence of detergent called the "Shindai Method". Using the protein solution
      consisting of hard alpha-keratins and matrix proteins prepared by this method, we
      developed two procedures for preparing hair protein films. The protein solution
      was mixed with trichloroacetic acid (TCA), perchloric acid (PCA) or guanidine-HCl
      (GHA), and then exposed in distilled water. Light brown aggregates immediately
      formed (Pre-cast method). The other method is based on the same characteristics
      of the hair proteins to form protein aggregates. The protein was directly exposed
      to the solution containing TCA, PCA, GHA, HCl, H(2)SO(4) or acetate buffer (Post
      cast method). The maximum yield was greater than 70%. These protein films were
      water-insoluble and mainly made up of alpha-keratins. Scanning electron
      micrographs showed that the fine surface of the protein films was composed of
      particles, filaments, and porous structures and the constitution was dependent on
      the preparation procedure used. When porcine intestine alkaline phosphatase (ALP)
      was mixed with the hair protein solution in a Post-cast method using acetate
      buffer (pH 5), ALP was incorporated into the alpha-keratin films. The activity
      retained in the protein film was approximately 8% of the original level. The
      biochemical properties of the ALP activity in the film were similar to those of
      the native enzyme.

PMID- 14709906
TI  - Establishment of an enzyme-linked immunosorbent assay for measurement of sotalol.
AB  - We have established an enzyme-linked immunosorbent assay suitable for routine
      monitoring of serum levels of sotalol. Anti-sotalol antibody was obtained by
      immunizing rabbits with sotalol conjugated with bovine serum albumin using the N
      succinimidyl ester method. An enzyme marker was similarly prepared by coupling
      sotalol with beta-D-galactosidase. The detection limit of sotalol by the enzyme
      linked immunosorbent assay was approximately 32 ng/ml with 50-microl samples.
      This assay was specific for sotalol because of very slight cross-reactivity with
      4-(methanesulfonylamino)benzonitrile (1.6%), but none with D,L-isoproterenol.
      Using this assay, drug levels were easily measured in the serum of rabbits after
      oral administration of sotalol at a single dose of 3 mg/kg. The enzyme-linked
      immunosorbent assay should be a valuable tool in therapeutic drug monitoring and
      pharmacokinetic studies of sotalol.

PMID- 14709907
TI  - Effect of cefixime and cefdinir, oral cephalosporins, on cytochrome P450
      activities in human hepatic microsomes.
AB  - The effects of two kinds of oral cephalosporins, cefixime and cefdinir, on
      cytochrome P450 (CYP) activities in human hepatic microsomes were investigated.
      Both cefixime and cefdinir at 2 mM concentration neither inhibited nor stimulated
      CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7
      hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9
      mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'
      hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation, CYP2E1-mediated
      chlorzoxazone 6-hydroxylation, CYP3A4-mediated nifedipine oxidation, or CYP3A4
      mediated testosterone 6beta-hydroxylation. The free fractions of cefixime and
      cefdinir in the incubation mixture, which were measured by ultracentrifugation,
      were 86.1-93.8% and 94.1-97.8%, respectively. These results suggest that both
      cefixime and cefdinir would not cause clinically significant interactions with
      other drugs, which are metabolized by CYPs, via the inhibition of metabolism.

PMID- 14709908
TI  - The carboxyl terminal sequence of rat transporter associated with antigen
      processing (TAP)-like (ABCB9) is heterogeneous due to splicing of its mRNA.
AB  - Transporter associated with antigen processing (TAP)-like (TAPL) is a half-type
      ATP-binding cassette (ABC) transporter with sequence similarity to TAP1 and TAP2
      and is highly conserved in mammals. Tissue distribution of the TAP family (TAP1,
      TAP2, TAPL) in rat was investigated using the semi quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). In young male rat, greater
      amounts of TAPL mRNA were detected in the brain and testis than in the thymus and
      intestine. On the other hand, both TAP1 and TAP2 mRNAs had higher expression in
      the thymus. Furthermore, the expression level of TAP1 in the intestine and that
      of TAP2 in the brain and testis were also high. Analysis of rat TAPL cDNAs
      demonstrated that the carboxyl terminal sequence of the ATP-binding region was
      heterogeneous. At least four different isoforms (C-I, -II, -III, -IV) could be
      produced by alternative splicing of mRNA, as was confirmed by a genomic data
      search. Both C-III and C-IV types had shorter carboxyl-terminal sequences, and
      the C-III had the shortest sequence. The functional heterogeneity of the carboxyl
      terminal splicing variants of TAPL is discussed.

PMID- 14709909
TI  - Susceptibility of mouse splenic cells to oxidative DNA damage by x-ray
      irradiation.
AB  - Susceptibility to oxidative stress by X-ray irradiation was examined in splenic
      cells of BDF1 mouse and fetal human lung fibroblasts, TIG-7. Survival rates of
      splenic cells irradiated with X-rays were lower than those of TIG-7 cells
      irradiated similarly. The content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG) immediately after X-ray irradiation in the DNA of splenic cells increased
      until 2 Gy irradiation, but remained constant above 2 Gy. The 8-oxodG contents
      rose in proportion to the dose of X-rays in TIG-7 cells. Although the survival
      rate of splenic cells exposed to 1 Gy irradiation decreased with time, the
      survival rate of TIG-7 cells remained unchanged. The 8-oxodG content in splenic
      cells irradiated with X-rays did not decrease even 48 h after irradiation, while
      that in TIG-7 cells decreased with time, and recovered to the pre-irradiation
      level after 48 h. A DNA ladder was observed in splenic cells 2 h after X-ray
      irradiation, but the ladder was not found in fibroblasts. Furthermore, caspase-3
      activity increased after X-ray irradiation of splenic cells. These results
      indicate that splenic cells are sensitive to oxidative stress induced by X-ray
      irradiation and that splenic cells damaged by even low doses of X-rays are
      removed through apoptosis rather than by a repair pathway.

PMID- 14709910
TI  - Activation of C-kinase eta through its cholesterol-3-sulfate-dependent
      phosphorylation by casein kinase I in vitro.
AB  - The physiological correlation between casein kinase I (CK-I) and an isoform eta
      of protein kinase C (C-kinase eta) was investigated in vitro, since it has been
      reported that (i) cholesterol-3-sulfate (CH-3S) effectively activates C-kinase
      eta rather than the other isoforms (C-kinase epsilon and C-kinase delta) in
      vitro; and (ii) CK-I efficiently phosphorylates CH-3S-binding proteins, such as
      high mobility group protein 1 (HMG1), in the presence of CH-3S in vitro. We found
      that (i) CK-I phosphorylated Thr in preference to Ser on recombinant human C
      kinase isoform eta (rhC-kinase eta) in the presence of CH-3S; (ii) this
      phosphorylation was selectively inhibited by CK-I-7 (a CK-I inhibitor); and (iii)
      the activity (phosphorylation of protamine sulfate) of rhC-kinase eta was approx.
      3.2-fold stimulated by its full phosphorylation by CK-I in the presence of 3
      microM CH-3S. These results suggest that CK-I is a protein kinase responsible for
      the activation of rhC-kinase eta in the presence of CH-3S in vitro.

PMID- 14709911
TI  - Pyroglutamyl aminopeptidase I, as a drug metabolizing enzyme, recognizes
      xenobiotic substrates containing L-2-oxothiazolidine-4-carboxylic acid.
AB  - Pyroglutamyl aminopeptidase I (PAP-I) is known for specifically removing the L
      pyroglutamate (L-pGlu) residue from the amino terminus of L-pGlu proteins and
      peptides. In general, substrate recognition of PAP-I as to L-pGlu moiety is
      tightly regulated. However, we recently identified PAP-I as a metabolic enzyme of
      an organic nitrate compound, RS-7897, which contains L-2-oxothiazolidine-4
      carboxylic acid (L-OTCA). L-OTCA is a latent sulfhydryl group, which has moiety
      structurally related to L-pGlu. In this study, we investigated the substrate
      specificity of PAP-I toward modified L-pGlu-containing substrates using
      recombinant rat, mouse and human PAP-Is. PAP-I was tolerant of replacement of a
      carbon atom at the 4-position of the L-pGlu moiety by a sulfur atom (L-OTCA), an
      oxygen atom (L-2-oxooxazolidine-4-carboxylic acid, L-OOCA) and an NH group (L-2
      oxoimidazolidine-4-carboxylic acid, L-OICA). The K(m) values for rat PAP-I in
      hydrolyzing L-pGlu-L-Ala, L-OTCA-L-Ala, L-OOCA-L-Ala and L-OICA-L-Ala were 0.057,
      0.43, 0.71 and 0.42 mM, respectively. Similar results were observed in mouse and
      human PAP-Is as well. Moreover, the hydrolysis of RS-7897 in rat and mouse liver
      cytosols were both completely inhibited by an antibody against rat PAP-I,
      strongly suggesting that PAP-I is solely involved in the hydrolysis of L-OTCA
      containing compounds in rat and mouse liver cytosols.

PMID- 14709912
TI  - Herbkines increases physical stamina in mice.
AB  - Herbkines has been used for the purpose of development of physical strength. In
      the present study, we investigated the effect of Herbkines on performance of the
      forced swimming test (FST) and on blood biochemical parameters related to
      fatigue: blood urea nitrogen (BUN), creatine kinase (CK), lactic dehydrogenase
      (LDH), glucose (Glc), and total protein (TP). Herbkines were orally administered
      to mice, 10 ml/kg, continuously once per day for 2 weeks using a feeding
      atraumatic needle. After 2 d, on FST, the immobility time was decreased in the
      Herbkines-fed group (178+/-8.2 s) in comparison with the control group (189+/-22
      s); however, the statistical difference was very weak (p=0.596). After 2 weeks,
      the immobility time was significantly decreased in the Herbkines-fed group (196+/
      4.5 s) in comparison with the control group (221+/-6.2 s). In addition, the
      content of BUN in the blood serum was significantly decreased. However, the
      levels of CK, LDH, Glc, and TP did not show a significant change. The results
      predict a potential benefit of Herbkines as an anti-fatigue treatment and for
      improving physical stamina.

PMID- 14709913
TI  - Inhibitory effects of long-term administration of ferulic acid on microglial
      activation induced by intracerebroventricular injection of beta-amyloid peptide
      (1-42) in mice.
AB  - Flavonoids and monophenolic compounds have been well described in recent years as
      antioxidants and scavengers of reactive oxygen and nitrogen species. In the
      present study, we aimed to characterize the effects of long-term administration
      of ferulic acid on the centrally administered beta-amyloid peptide (Abeta)(1-42)
      induced activation of microglial cells in mice. Abeta(1-42) increased the
      immunoreactivity of OX-42, a microglial marker, and interferon-gamma in the
      hippocampus at 8 h after the intracerebroventricular injection. The effects were
      suppressed by long-term (4-week) pretreatment with ferulic acid. This inhibition
      of microglial cell activation may underlie the beneficial effects of long-term
      administration of ferulic acid on Abeta(1-42)-induced toxicity in vivo.

PMID- 14709914
TI  - Potentiated modulation of pregnolone on GABAA receptors in behaviorally stressed
      borderline-hypertensive rats.
AB  - The modulatory effects of behavioral stress on [(3)H]flunitrazepam, an agonist
      for the central-type benzodiazepine receptor binding to the GABA(A)
      benzodiazepine receptor complex, in borderline hypertensive rats (BHR) were
      examined. In repeatedly immobilized (for 2 weeks, for 2 h/d) BHR, enhancement of
      [(3)H]flunitrazepam binding to the receptor was observed to be potentiated. The
      percent enhancement of [(3)H]flunitrazepam binding in BHR was higher than that in
      normotensive control Wistar-Kyoto rats. Pregnanolone, a neuroactive steroid that
      has been reported to be a putative endogenous modulator in the stress response,
      concentration dependently enhanced [(3)H]flunitrazepam binding to the receptor.
      Enhancement of [(3)H]flunitrazepam binding was observed to be potentiated by the
      same immobilized stress, and the EC(50) values of pregnanolone in BHR was
      significantly lower than those in controls and E(max) values were higher. From
      the above results, it can be concluded that neural modulation to behavioral
      stress, especially in GABAergic neurotransmission, is exaggerated in BHR. We
      propose strain-specific differences of stress reactivity as an important
      pathogenetic factor in psychosomatic disorders including stress-induced
      hypertension. This is supported by reports showing exaggerated cardiovascular and
      symathoadrenal responses to stress in BHR.

PMID- 14709915
TI  - Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats.
AB  - The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia
      forficata was investigated in a model of alloxan-induced diabetes in rats. The
      biochemical parameters studied were: plasma glucose, serum triglycerides,
      cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL).
      Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48
      h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed
      significant reductions in plasma glucose, triglycerides, total cholesterol and
      HDL-cholesterol after treatment with the extracts and glibenclamide (used as
      standard) as compared to the diabetic controls. Levels of LDL were not altered.
      In conclusion, our results showed that the plant extracts when administered by
      gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol
      levels. These results suggest the validity of the clinical use of B. forficata in
      the treatment of diabetes mellitus type II.

PMID- 14709916
TI  - Drug-drug interactions between antiarrhythmic drugs in chick embryos.
AB  - The drug-drug interactions between antiarrhythmic drugs were studied in chick
      embryos. Fertilized eggs of White Leghorns were incubated and investigated.
      Procainamide or flecainide with and without propranolol was injected into the air
      sac of a fertilized egg. Electrocardiograms (ECGs) were recorded 0 to 60 min
      after the injection. After each drug injection alone, the heart rate was not
      different compared with the control. However, the heart rate was significantly
      decreased by combinations of procainamide and propranolol or flecainide and
      propranolol. In addition, arrhythmia was produced in combination with
      propranolol. These findings indicate that the drug-drug interactions between
      antiarrhythmic drugs have a marked influence on the heart rate in chick embryos.

PMID- 14709917
TI  - Lack of action potential-prolonging effect of terfenadine on rabbit myocardial
      tissue preparations.
AB  - The effects of terfenadine, an antiallergic drug also known for its QT-prolonging
      and arrhythmogenic activities, on the action potential of isolated myocardial
      tissue preparations from rabbits were examined with microelectrode techniques. In
      the Purkinje fibers and atrium, terfenadine concentration dependently decreased
      the maximum rate of rise (+.V(max)) without affecting other action potential
      parameters. In the ventricle, terfenadine had little effect on action potential
      configuration. In the sinoatrial node, terfenadine 20 microM prolonged cycle
      length mainly through inhibition of +.V(max). Terfenadine 1 microM completely
      inhibited the human ether a go-go-related gene (HERG) channel current expressed
      in HEK293 cells in the same experimental solution as in microelectrode
      experiments. The lack of terfenadine effect on the action potential duration
      suggests that there are drugs for which the HERG channel inhibitory action
      underlying in vivo QT prolongation cannot be evaluated based on their action
      potential-prolonging activity in isolated myocardial tissue preparations.

PMID- 14709918
TI  - Effects of benzyl glucoside and chlorogenic acid from Prunus mume on
      adrenocorticotropic hormone (ACTH) and catecholamine levels in plasma of
      experimental menopausal model rats.
AB  - To investigate the effectiveness of benzyl beta-D-glucopyranoside (BG) and
      chlorogenic acid (CA), the constituents of the fruit of Prunus mume, for
      relieving tension in experimental menopausal model rats (M-rats) caused by ether
      stress, the effects of BG and CA on adrenocorticotropic hormone (ACTH) and
      catecholamine (adrenaline, noradrenaline, and dopamine) levels were examined in
      the plasma of M-rats. Caffeic acid, quinic acid, and rosmarinic acid, which are
      compounds structurally related to CA, were also examined. BG obviously recovered
      catecholamine levels decreased by ether stress and increased dopamine to high
      levels. On the other hand, CA significantly decreased the ACTH level increased by
      ether stress and showed the greatest effect of all compounds. These results
      suggest that BG and CA may contribute to relieving the tension in M-rats caused
      by ether stress.

PMID- 14709919
TI  - 5-Hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone: a pancreatic
      lipase inhibitor isolated from Alpinia officinarum.
AB  - A pancreatic lipase inhibitor, 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl
      3-heptanone (HPH), from the rhizome of Alpinia officinarum (AO) was isolated and
      its antihyperlipidemic activity was measured. HPH inhibited a pancreatic lipase
      with an IC(50) value of 1.5 mg/ml (triolein as a substrate). HPH significantly
      lowered the serum TG level in corn oil feeding-induced triglyceridemic mice, and
      reduced serum triglyceride (TG) and cholesterol in Triton WR-1339-induced
      hyperlipidemic mice. However, HPH did not show hypolipidemic activity in high
      cholesterol diet-induced hyperlipidemic mice. Based on these findings, we propose
      that PL inhibitors may be effective as hypolipidemic agents.

PMID- 14709920
TI  - Trypanocidal constituents in plants 3. Leaves of Garcinia intermedia and
      heartwood of Calophyllum brasiliense.
AB  - The constituents of the leaves of Garcinia intermedia and heartwood of
      Calophyllum brasiliense were investigated based on their trypanocidal activity
      against epimastigotes of Trypanosoma cruzi, the etiologic agent of Chagas'
      disease. As the active components, the polyisoprenylated benzophenone derivative
      guttiferone A and the xanthone 8-desoxygartanin were isolated along with the
      biflavonoids podocarpusflavone A and amentoflavone, and friedelin from the
      former. Three xanthones, jacareubin, 6-deoxyjacareubin, and 1,3,5,6-tetrahydroxy
      2-(3-methyl-2-butenyl)xanthone from the latter showed activity. The trypanocidal
      activity of these compounds against trypomastigotes, an infectious form of T.
      cruzi, was examined as well as gossypol, berberine chloride, and harmine for
      comparison.

PMID- 14709921
TI  - Application of single-nucleotide polymorphism analysis of the trnK gene to the
      identification of Curcuma plants.
AB  - We previously found that Curcuma plants and drugs derived from Curcuma longa, C.
      phaeocaulis, C. zedoaria, and C. aromatica could be identified by the nucleotide
      differences at two sites and the existence of a 4-base indel on trnK gene. In
      this paper, based on species-specific nucleotide sequences, the application of a
      new method, single-nucleotide polymorphism (SNP) analysis was investigated to
      identify Curcuma plants more conveniently. First, three types of reverse primer
      were synthesized in different lengths, 34 mer, 26 mer, and 30 mer, to anneal the
      template DNAs from each species at sites immediately upstream from substitution
      positions 177 and 645, and at the site including the 4-base insertion from 728 to
      731, respectively. After single-base extension reaction of these primers using
      fluorescent-labeled ddNTPs and PCR products of the trnK gene region as template,
      the resulting products were detected using an ABI PRISM 310 Genetic Analyzer. The
      electrophoretogram showed three or two peaks at different positions depending on
      the 27 mer, 31 mer, and 35 mer product lengths. Each peak was derived from the
      incorporated fluorescent-labeled ddNMPs complementary to template nucleotides at
      positions 645, 724, and 177, respectively. C. phaeocaulis showed three peaks of
      ddCMP, ddAMP, and ddAMP. The other three species showed two peaks derived from 27
      mer and 35 mer products: peaks of ddCMP and ddAMP in C. longa, those of ddCMP and
      ddTMP in C. zedoaria, and those of ddTMP and ddAMP in C. aromatica. Thus SNP
      analysis to identify four Curcuma plants was newly developed.

PMID- 14709922
TI  - Statistical trial designs and clinical practice: are they compatible?

PMID- 14709923
TI  - Statistical principles: myths or facts?

PMID- 14709924
TI  - Consent and equipoise, the crucial ethical issues in randomised clinical trials.
AB  - Randomised clinical trials are widely accepted as the gold standard of clinical
      research. They seem to be the only means of conclusively establishing a
      relationship between an intervention and an observed outcome. However,
      randomisation by definition rules out individual choice of a treatment option.
      The justification of randomising is that the different options are in equipoise,
      and therefore no patient is at a disadvantage in the trial. There is concern
      whether equipoise, in a strict sense, is at all possible. This would require that
      there is no evidence as to the comparative efficacy of the treatments to be
      tested. This condition is in contrast to an honest null hypothesis. Several
      suggestions have been made to solve the tension of the equipoise requirement and
      are discussed in this paper. The second important condition for randomised
      clinical trials is to obtain informed consent from the patient. Valid consent
      requires that it is given voluntarily by a competent person who is adequately
      informed.

PMID- 14709925
TI  - Clinical research and industrial sponsoring: avenues towards transparency and
      credibility.
AB  - Clinical research is intended to serve the patient, in the pursuit of a deepened
      understanding of physiological interactions and their changes in disease, and of
      potentially beneficial implications for the patient. The impetus to perform
      clinical research is shaped by various intentions, such as the desire to provide
      cure or relief, striving for personal and professional success, public attention,
      financial considerations, or simply scientific curiosity. A similarly wide range
      of diverging interests must be assumed to impinge on diagnostic and therapeutic
      decisions in clinical work. How are we to perform clinical research and therapy
      with the patients' benefit in mind, in view of such a complex motivational
      status, and how are we to perceive the peculiar interests of those influencing
      clinical work, including ourselves? In this review, we attempt to elucidate the
      complex pathways of interaction between physicians and industrial sponsors.
      Special attention will be paid to the following topics: the pharmaceutical
      market, public interests, legal and ethical issues, conflicts of interest, and
      the potential impact of industry-sponsored drug trials on medical information and
      subsequent therapeutic decisions. We will conclude with recommendations for an
      acceptable position in the tension between cooperation and corruptibility, a
      position that grants priority to the patient's needs rather than third party
      interests.

PMID- 14709926
TI  - Malpractice in oncology.
AB  - In oncology, as in all other medical disciplines, medical malpractice is assumed
      when the physician has not taken sufficient care in his treatment, and when he
      has not met the required standards of medical care. The physician is liable for
      damages when distinct harm has arisen from this. In oncology, accusations of
      malpractice arise especially when suspicion of a malignancy is not based on
      unequivocal substantive diagnostic criteria (for example, the appropriate
      appraisal of routine x-rays or screening scans), or in terms of organizational
      mistakes. Stringent safeguards in oncological diagnostics and therapy are usually
      based on approved and generally recognized guidelines. From the time that the
      malignancy is suspected, there is therefore little concrete danger that
      malpractice will be attested provided these guidelines are complied with. The
      tolerance accorded by experts in respect of intraoperative complications in
      oncological operations appears to be great amongst medical expert witnesses. If a
      malpractice is attested, the distinct damage resulting from this can only be
      appraised approximately, e.g. by comparing the statistical probability of
      survival in various tumor stages.

PMID- 14709927
TI  - Typical medication errors in oncology: analysis and prevention strategies.
AB  - Pharmacotherapy in oncology is complex. It has a small therapeutic range, and is
      susceptible to errors. Medication errors--especially overdosage--often have
      serious effects while underdosage entails unnoticed impairment of the therapeutic
      success. Typical medications and procedures susceptible to errors are described:
      unintentional intrathecal injections, the application of platinum compounds and
      anthracyclines, confusion of total and single dose, errors of calculation and
      preparation, or in operation of infusion pumps. Suitable prevention strategies
      are standardisation, separation of intrathecal and intravenous chemotherapy, and
      use of specialized software for planning and calculating chemotherapy, as well as
      non-punitive notification and recording systems for errors and near-errors in
      treatment.

PMID- 14709928
TI  - Error prevention and error management in medicine--adopting strategies from other
      professions.
AB  - The report of the Institute of Medicine (IOM) 'To Err Is Human' received public
      interest. The simple term 'medical error' as it has been used in public so far
      does not describe the complex setting in medicine. The development of error
      management in industry (e.g. aviation) with an emphasis on human factors,
      communication, and systematic error is demonstrated in order to design similar
      approaches for medicine. Recommendations are based on the principles for
      designing safety systems in health care organisations published in the IOM
      report.

PMID- 14709929
TI  - Randomized clinical trial: myths around elementary statistical principles.
AB  - In discussing design and results of randomized clinical trials, in particular
      with clinical oncologists, one often encounters the opinion that a phase III
      trial is a complicated, highly costly, and difficult task. Part of this opinion
      seems to originate in myths around underlying biostatistical principles such as
      randomization, sampling and sample size, statistical hypotheses, statistical
      error probabilities, and statistical power. This work clarifies basic statistical
      issues of randomized clinical trials and the interpretation of their results. Six
      issues ('myths') relevant for the design of clinical trials and the
      interpretation of their results are addressed. They concern choice of study
      design, choice of participating centers, and recruitment of patients as well as
      statistical questions of establishing study hypotheses and interpreting p values.
      These myths are shown to be caused primarily through a misunderstanding of
      statistical inference and statistical thinking that can be avoided when a
      rational understanding of statistical principles is translated into a clinical
      research approach. We also conclude that before clinical evidence is summarized
      from different studies each study should be examined thoroughly.

PMID- 14709930
TI  - Coping of cancer patients during and after radiotherapy--a follow-up of 2 years.
AB  - AIM: We wanted to understand coping strategies specific to different phases up to
      two years after radiotherapy, to identify patients who are at higher risk of mood
      disturbances and to characterise the association between coping strategies and
      psychosocial adaptation. PATIENTS AND METHODS: From 1997 to 2001, 2,169 patients
      with different diagnoses were screened (27.8% refused to participate). Data of
      276 patients from the beginning of radiotherapy (ti1) and 5 follow-up
      investigations (ti6/2 years) could be analysed. With the FKV (Freiburg
      Questionnaire Coping with Disease) cancer-specific coping aspects were assessed.
      The association between coping styles and psychosocial adaptation was evaluated
      using the Questionnaire on Stress in Cancer Patients (QSC) and the questionnaire
      on Functional Assessment of Cancer Treatment (FACT-G). RESULTS: 'Active problem
      orientated' coping and 'distractions' are the most important coping strategies.
      Only 'active problem-orientated' and 'depressive' coping showed a significant
      decrease. We observed higher means on the scales of the FKV in women. Marital
      status (single, married, divorced/widowed) had a significant influence on active
      problem-orientated coping and spirituality. Age, children, education, T/M status
      and curative/ palliative intention of treatment had no influence on coping
      styles. Breast cancer patients and lymphoma patients demonstrated the highest use
      of coping strategies after radiotherapy with a significant decrease of 'active
      problem-orientated coping'. Depressive coping and minimizing importance at ti1
      were associated with high psychosocial distress and low quality of life (QoL) at
      ti6. CONCLUSION: The correlation of coping mechanisms at the beginning of
      radiotherapy with low QoL and high psychosocial stress at 2 years could help to
      identify patients at risk for low psychosocial adaptation. Psycho-oncologically
      trained teams of physicians would best correspond to this profile of needs and
      would contribute significantly to an ameliorated adaptation of patients to cancer
      which could lead to higher life satisfaction.

PMID- 14709931
TI  - Impact of inguinal dissection on prognosis of early-stage squamous cell carcinoma
      of the vulva--a retrospective analysis.
AB  - BACKGROUND: Inclusion of inguinal lymphadenectomy in the surgical procedure is a
      potential prognostic factor for squamous cell vulvar carcinoma. PATIENTS AND
      METHODS: A total of 33 women with early-stage squamous cell vulvar carcinoma were
      analyzed retrospectively. Before the establishment of FIGO criteria in 1983, 17
      patients with stage I and 2 patients with stage II were evaluated clinically
      without inguinal lymphadenectomy. All patients underwent post-operative
      radiotherapy with a median dose of 45 Gy to the pelvis (vulva included) and boost
      dose to the vulva ranging from 10 to 20 Gy. Factors assessed for prognostic value
      included age, inguinal lymph node dissection, differentiation grade, and total
      irradiation dose to the vulva and pelvis. RESULTS: The log-rank test and the
      univariate regression analysis revealed that all above factors except irradiation
      dose decreased the overall survival. In the multivariate regression analysis,
      differentiation grade and the absence of inguinal dissection were independent
      predictors for decreased survival with a relative risk up to 2.6 (95% CI = 1.3,
      5.6) and 2.7 (95% CI = 1.31, 5.44), respectively. CONCLUSION: Clinical evaluation
      of inguinal lymph node involvement is inadequate and node dissection is
      definitely the only appropriate surgical procedure for vulvar carcinoma.

PMID- 14709932
TI  - Weekly paclitaxel and carboplatin combination chemotherapy in patients with
      advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The combination of paclitaxel and carboplatin is active in the
      treatment of squamous cell carcinoma of the head and neck (SCCHN). However,
      considerable toxicity develops with 3-weekly drug administration. Treatment on a
      weekly basis may allow for a higher dose intensity with less adverse effects.
      PATIENTS AND METHODS: Enrolled in this study were 31 patients with locally
      advanced, metastatic or relapsed SCCHN, most of them pretreated. They received
      weekly i.v. infusions of 80 mg/m(2) paclitaxel over 1 h combined with carboplatin
      at an area under the concentration time curve of 2 mg/ml/min over 30 min.
      RESULTS: The overall response rate was 52% with 1 complete response and 16
      partial responses. Median progression-free survival was 5.4 months, median
      overall survival 12.8 months. Grade 3/4 hematologic adverse events occurred in 7
      patients and grade 3 peripheral neuropathy in one. 10 patients required dose
      reduction or treatment delay due to neutropenia, thrombocytopenia or neuropathy.
      CONCLUSIONS: Weekly administration of paclitaxel and carboplatin appears to be
      safe and efficacious in patients with advanced, metastatic or recurrent SCCHN.

PMID- 14709933
TI  - Relapse after high-dose therapy in relapsed Ewing's tumor patients: effects of
      maintenance chemotherapy in two selected patients?
AB  - BACKGROUND: The prognosis for patients with high-risk Ewing's tumor, i.e.
      primarily multifocal or early relapsed disease, is extremely poor with
      conventional relapse therapy. High-dose radio/chemotherapy (HDC) with subsequent
      stem cell transplantation seems to improve outcome in this patient cohort. In
      spite of this intensified therapy however, relapse remains the most frequent
      cause of death. In the majority of patients the time to second relapse after HDC
      is shorter than the time to first relapse after conventional therapy (3.4 vs. 18
      months). Event-free survival in Ewing's tumor patients who suffer a second
      relapse after first-line therapy (EICESS 92) is 2% after 18 months. CASE REPORT:
      The present report describes the clinical course of two girls who relapsed after
      HDC and subsequently received low-dose oral trofosfamide and etoposide. The
      patient with very late multifocal relapse after first-line treatment and a second
      localized relapse 30 months after HDC remains disease-free for 5 years after the
      last relapse. However, the other patient with 2 early relapses after first-line
      treatment and HDC, respectively, did not benefit from this regime. CONCLUSION: We
      propose that low-dose maintenance therapy may be beneficial in the subgroup of
      Ewing's tumor patients with late relapse after HDC.

PMID- 14709934
TI  - Capecitabine as salvage therapy for a breast cancer patient with extensive liver
      metastases and associated impairment of liver function.
AB  - BACKGROUND: Breast cancer metastasizing to the liver with presence of a
      parenchymatous icterus presents a therapeutic dilemma. Treatment-related toxicity
      can be unpredictable due to altered drug clearance, and bilirubin exceeding 5,0
      mg/dl is generally considered an absolute contraindication for the administration
      of cytotoxic agents. The pharmacokinetics of capecitabine--an active oral 5
      fluorouracil prodrug for the treatment of advanced breast cancer--are not
      affected in patients with mild to moderate hepatic dysfunction, but there are no
      data available for patients with severe hyperbilirubinemia. PATIENT AND METHODS:
      We herein report the case of a female patient with advanced breast cancer with
      predominant liver metastases and severe hyperbilirubinemia (12 mg/dl). The
      patient received oral capecitabine at a dose of 2,500 mg/m2/day in 2 divided
      doses for 2 weeks, followed by 1 week rest. RESULTS: Several assessments of liver
      function parameters including serum bilirubin showed a decrease to normal values
      within 2.5 months. After 7 courses of treatment, a partial remission was
      confirmed by CT scan. Treatment with capecitabine was well tolerated with grade 2
      hand-and-foot syndrome and mild nausea being the only side effects. CONCLUSION:
      This case report suggests that capecitabine can be safely administered without
      dose adjustment in patients with extensive liver metastases and hepatic
      dysfunction.

PMID- 14709935
TI  - Drug resistance in human melanoma: mechanisms and therapeutic opportunities.
AB  - In malignant melanoma chemotherapy is very ineffective. This poor prognosis
      largely results from resistance to conventional chemotherapy. The cellular
      mechanisms involved in melanoma chemoresistance have yet to be fully elucidated.
      The relevance of well analyzed drug-resistance mechanisms such as intra
      /extracellular transport, drug-resistance by induction of certain enzyme systems
      and DNA repair is reviewed. The results of many studies suggest that drug
      resistance in melanoma is most likely caused by a dysregulation of apoptotic
      processes. Identification of genes and gene products that are responsible for
      apoptosis, together with emerging information about the mechanism of action and
      structures of apoptotic regulatory and effector proteins, has laid a foundation
      for the discovery of drugs, some of which are now undergoing evaluation in human
      clinical trails for melanoma treatment. The complexity of the molecular variants
      involved in signal transduction along apoptotic pathways suggests that the cell
      may have a variety of possibilities for regulating apoptosis and generating
      apoptosis deficiency. However, identification of drug resistance mechanisms
      provides new therapeutic targets to overcome chemoresistance in this and other
      malignancies.

PMID- 14709937
TI  - A novel mobile device for intraoperative radiotherapy (IORT).

PMID- 14709936
TI  - Ductal carcinoma in situ of the breast: diagnosis and management.
AB  - Currently, no precise morphologic or biologic prognostic factors reliably
      identify patients with ductal carcinoma in situ (DCIS) who are at high risk of
      disease progression. DCIS is a disease with an extremely favorable prognosis and
      a small likelihood of dying from breast cancer, regardless of what type of
      treatment is received. No retrospective or prospective study to date has
      demonstrated a significant difference in breast cancer specific mortality
      regardless of treatment. The similarities between DCIS and invasive cancer
      suggest that an important area for future research should be elucidating the
      processes that can either unleash or contain the invasive potential of DCIS
      cells. Thus, an understanding of the biology of DCIS can assist in the
      prevention, the assessment, and the diagnosis of invasive breast cancer.

PMID- 14709938
TI  - Tension-free vaginal tape efficacy in relation to collagen quantity of
      pubocervical fascia.
AB  - OBJECTIVE(S): To investigate whether the quantity of collagen types I and III in
      the pubocervical fascia of women with genuine stress incontinence (GSI) affects
      the efficacy of the tension-free vaginal tape (TVT) procedure. METHODS: Sixty
      three patients participated in the study and were divided in 2 groups as follows:
      37 patients with GSI and pelvic organ prolapse stage I (group 1), and 26 patients
      with pelvic organ prolapse stage I but not GSI (control group). Urodynamic
      studies confirmed the diagnosis of GSI. Biopsies were obtained during surgery
      from the pubocervical fascia. RESULTS: The quantity of collagen types I and III
      was statistically significantly reduced in patients with GSI compared to the
      control group. The efficacy of the TVT procedure in patients with a significant
      reduction in collagen type I was an 82.1% cure. In patients with a significant
      reduction in collagen type III, the TVT efficacy was an 85.1% cure. The efficacy
      of the TVT procedure was not statistically significantly different between
      patients with GSI and a significant reduction in collagen types I and III, and
      patients with no reduction in collagen types I and III. CONCLUSIONS: The
      significantly reduced quantity of collagen types I and III in the pubocervical
      fascia of women with GSI does not affect the efficacy of the TVT procedure at an
      average of 25 months of follow-up.

PMID- 14709939
TI  - Dosing strategies for antidepressant clinical trials: a commentary.

PMID- 14709940
TI  - Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and
      nefazodone in healthy volunteers.
AB  - An antidepressant for use in the patient receiving concomitant drug treatment,
      over-the-counter medications, or herbal products should lack cytochrome P-450
      (CYP) 3A4 inductive or inhibitory activity to provide the least likelihood of a
      drug-drug interaction. This study addresses the potential of 4 diverse
      antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit
      or induce CYP3A4. In a 4-way crossover design, 16 subjects received clinically
      relevant doses of venlafaxine, nefazodone, or sertraline for 8 days or fluoxetine
      for 11 days. Treatments were separated by a 7- to 14-day washout period and
      fluoxetine was always the last antidepressant taken. CYP3A4 activity was
      evaluated for each subject at baseline and following each antidepressant using
      the erythromycin breath test (EBT) and by the pharmacokinetics of alprazolam
      (ALPZ) after 2-mg dose of oral ALPZ. Compared to baseline, venlafaxine,
      sertraline, and fluoxetine caused no apparent inhibition or induction of
      erythromycin metabolism (P > 0.05). For nefazodone, a statistically significant
      inhibition was observed (P < 0.0005). Nefazodone was also the only antidepressant
      that caused a significant change in ALPZ disposition, decreasing its area under
      the concentration-versus-time curve (AUC; P < 0.01), and increasing its
      elimination half-life (16.4 vs. 12.3 hours; P < 0.05) compared with values at
      baseline. No significant differences were found in the pharmacokinetics of ALPZ
      with any of the other antidepressants tested. These results demonstrate in vivo
      that, unlike nefazodone, venlafaxine, sertraline, and fluoxetine do not possess
      significant metabolic inductive or inhibitory effects on CYP3A4.

PMID- 14709941
TI  - Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol)
      levels and clinical responses with respect to milnacipran versus paroxetine
      treatment.
AB  - The purpose of this study was to investigate the effects of milnacipran and
      paroxetine on plasma levels of catecholamine metabolites, and we attempted to
      elucidate the differences between the mechanisms of these drugs in
      catecholaminergic neurons. In depressed patients, we investigated the
      relationships among pretreatment levels of catecholamine metabolites, the changes
      in plasma catecholamine metabolite levels before and after administration of
      milnacipran or paroxetine, and clinical response to these drugs. Responders to
      milnacipran showed lower pretreatment levels of plasma 3-methoxy-4
      hydroxyphenylglycol (pMHPG) than did nonresponders to milnacipran; there was also
      a positive correlation between changes in pMHPG levels and percent improvement of
      the score on the 17-item Hamilton Rating Scale for Depression (HRSD). On the
      other hand, responders to paroxetine showed higher pretreatment levels of pMHPG
      than did nonresponders to paroxetine, and a negative correlation was observed
      between changes in pMHPG levels and percent improvement of the HRSD score.
      However, a significant difference was not observed in the pretreatment plasma
      level of homovanillic acid between responders and nonresponders to treatment with
      milnacipran or paroxetine. These results suggest that there is an association
      between baseline pMHPG levels and clinical responses with respect to milnacipran
      versus paroxetine treatment.

PMID- 14709943
TI  - Meta-analysis of the efficacy of methylphenidate for treating adult attention
      deficit/hyperactivity disorder.
AB  - This article reviews the efficacy of methylphenidate (MPH) for adult attention
      deficit/hyperactivity disorder (ADHD). A literature search identified double
      blind placebo-controlled MPH treatment studies of ADHD adults. Meta-analysis
      estimated the pooled effect size for MPH treatment and tested for publication
      bias. Meta-analysis regression assessed the influence of study design features on
      medication effects. Six trials met criteria and were included in this meta
      analysis. These studies included a total of 140 MPH-treated ADHD adults and 113
      placebo-treated ADHD adults. The mean effect size of 0.9 was statistically
      significant and there was no evidence of publication bias. Larger MPH effect
      sizes were associated with physician ratings of outcome and use of higher doses.
      When treatment is optimized to high doses, the effect size for MPH in adults was
      1.3. We found strong support for the assertion that MPH is efficacious for
      treating adult ADHD. Because the degree of efficacy of MPH in treating ADHD
      adults is similar to what has been reported from meta-analyses of the child and
      adolescent literature, our work provides further assurance to clinicians that the
      diagnosis of ADHD can be validly applied in adulthood.

PMID- 14709942
TI  - Platelet serotonergic predictors of clinical improvement in obsessive compulsive
      disorder.
AB  - OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the most efficient
      pharmacological treatment of obsessive-compulsive disorders (OCD). Previous
      studies have suggested that some peripheral serotonergic parameters can be used
      to predict the clinical outcome of the treatment of OCD patients with SRIs. We
      tried to identify further peripheral serotonergic parameters that could help
      predict the clinical outcome of SRI treatment in a sample of patients with OCD.
      METHODS: We compared 19 OCD patients before and after 8 weeks of SRI treatment
      with 19 sex-matched and age-matched controls. We assessed clinical improvement
      and whole-blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT)
      and 5-HT2A receptor binding characteristics and platelet IP3 content. RESULTS:
      Before treatment, OCD patients had higher platelet IP3 content and fewer 5-HTT
      binding sites than the controls. Treatment with SRIs further lowered the number
      of 5-HTT binding sites, normalized platelet IP3 contents, and lowered the number
      of platelet 5-HT2A binding sites and whole-blood 5-HT concentrations below
      control values. The patients who improved most following SRI treatment had higher
      whole-blood 5-HT concentrations before treatment. CONCLUSION: Our results confirm
      that whole-blood 5-HT concentration is a predictor for clinical improvement and
      indicate that abnormal intracellular mechanisms may be involved in OCD patients,
      in particular, the overstimulation of the phosphoinositide signaling system.

PMID- 14709944
TI  - Changes in symptoms and adverse events after discontinuation of atomoxetine in
      children and adults with attention deficit/hyperactivity disorder: a prospective,
      placebo-controlled assessment.
AB  - Drugs that affect neurotransmitter release can induce changes in neuroregulation
      during chronic administration. Thus, in addition to recurrence of symptoms of the
      illness, discontinuation of treatment can be associated with clinical signs and
      symptoms related to these changes. Atomoxetine, a new drug approved in the United
      States for treatment of attention deficit/hyperactivity disorder (ADHD), is
      associated with blockade of the presynaptic norepinephrine transporter. Because
      treatment of ADHD typically involves chronic treatment, the potential for
      production of a discontinuation syndrome as well as recurrence of symptoms upon
      drug discontinuation were assessed as part of the clinical development process.
      The effects of discontinuation of atomoxetine were assessed in children and
      adults with ADHD following 9 to 10 weeks of continuous therapy in 4 large
      studies. Symptoms of ADHD worsened following drug discontinuation but did not
      return to pretreatment levels. The incidence of discontinuation-emergent adverse
      events was low and there were no statistically significant differences between
      the patients abruptly discontinuing from atomoxetine and those continuing on
      placebo. Discontinuation of atomoxetine did not result in the development of an
      acute discontinuation syndrome and was well tolerated. It appears that
      atomoxetine may be discontinued without risk for symptom rebound or
      discontinuation-emergent adverse effects. Tapering of doses is not necessary when
      atomoxetine is discontinued.

PMID- 14709945
TI  - Effects of once-daily osmotic-release methylphenidate on blood pressure and heart
      rate in children with attention-deficit/hyperactivity disorder: results from a
      one-year follow-up study.
AB  - OBJECTIVE: Studies of vital signs in children and adolescents with attention
      deficit/hyperactivity disorder (ADHD) receiving stimulants indicate a variable
      effect on blood pressure (BP) and heart rate (HR). We evaluated the longer-term
      effects on vital signs of once-daily osmotic-release methylphenidate (MPH,
      Concerta) in children with ADHD. METHODS: As part of a 1-year open-extension
      trial, we studied children with ADHD (aged 6-13 years; baseline assessment, n =
      432) who were entered into an open-label study of osmotic-release MPH (18-54 mg)
      for up to 1 year. Subjects' BP and HR were recorded at monthly visits and, when
      applicable, analyses were by last observation carried forward. RESULTS: Compared
      to off-drug baseline, osmotic-release MPH was associated with minor clinical,
      although statistically significant, changes in systolic and diastolic blood
      pressure (DBP) (3.3 and 1.5 mm Hg, Ps < 0.001) and HR (3.9 bpm, P < 0.0001) at 12
      month end point. There was no clear dose-response relationship. There was no
      tolerance to the pressor effects of osmotic-release MPH over the 1-year period.
      There was an inverse relationship between baseline vital signs and positive
      change in vital signs at end point. CONCLUSIONS: Over a 12-month period, osmotic
      release MPH produced minor clinical, although statistically significant, changes
      in BP and HR in children with ADHD.

PMID- 14709946
TI  - Predictors of response in generalized social phobia: effect of age of onset.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the
      pharmacological treatment of generalized social phobia (GSP). However, little is
      known about the predictors of response to treatment. Two hundred and four
      outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20
      week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d.
      Response was defined as the percentage of patients with a Clinical Global
      Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much
      improved). Outcome analyses were conducted using regression models including
      treatment group as a categorical predictor and study visit as a repeated measure.
      Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia
      Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several
      possible predictors of response to treatment including DSM-IV comorbidity, age,
      sex, age of onset of GSP, and duration of illness. Patients with later-onset
      (especially adult-onset) GSP tend to have a better response to treatment than
      those with earlier-onset GSP. This result generally appears in our analyses as a
      2-way interaction, where the association with response is greatest for patients
      with adult-onset GSP (in contrast to those with child or adolescent onset). This
      finding is most robust for symptom measures, but is still apparent for the
      Sheehan measure of disability at work. This advantage for later-onset GSP can be
      accounted for neither by severity of illness nor by duration of illness. Superior
      treatment outcome for later-onset GSP may be mediated by the degree of social and
      family disability.

PMID- 14709947
TI  - A double-blind placebo-controlled study of controlled release fluvoxamine for the
      treatment of generalized social anxiety disorder.
AB  - This was a randomized double-blind placebo-controlled multicenter study to assess
      the efficacy, safety, and tolerability of fluvoxamine in a controlled release
      (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A
      total of 300 subjects with GSAD were randomly assigned to receive either
      fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from
      baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global
      Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as
      well as the mean end point scores in Clinical Global Impression Improvement Scale
      (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared
      between the fluvoxamine CR and placebo treatment groups. Arizona Sexual
      Experience Scale (ASEX), adverse event, and other safety parameters were also
      assessed. The results demonstrated that fluvoxamine CR was significantly superior
      to placebo in decreasing LSAS total score (primary measure) starting at week 4.
      At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37%
      reduction) in the LSAS total score in the fluvoxamine CR group compared with 
      27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change).
      Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at
      end point (secondary measures). When compared with placebo, fluvoxamine CR did
      not cause any significant weight gain or clinically significant sexual
      dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious,
      safe, and well-tolerated treatment of generalized social anxiety disorder.

PMID- 14709948
TI  - A randomized open-label study of the impact of quetiapine versus risperidone on
      sexual functioning.
AB  - OBJECTIVE: To compare sexual functioning in patients treated with quetiapine or
      risperidone. METHODS: This open-label study included patients with schizophrenia
      or a related psychotic illness who were randomized to quetiapine (200-1200 mg/d)
      or risperidone (1-6 mg/d) for 6 weeks. Sexual dysfunction was assessed by a
      semistructured interview, the Antipsychotics and Sexual Functioning Questionnaire
      (ASFQ), based upon the Utvalg for Kliniske Undersogelser (UKU). RESULTS: Four of
      25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients
      (50%) reported sexual dysfunction (chi 2 = 6.4; df = 1; P = 0.006) on the ASFQ.
      Six patients (11.7%; 4 on risperidone, 2 on quetiapine) spontaneously reported
      sexual dysfunction. The mean+/-SD dose was 580+/-224 mg/d for quetiapine and 3.2
      +/- 1.3 mg/d for risperidone. Mean +/- SD prolactin levels in quetiapine- and
      risperidone-treated patients were 13.8 +/- 17.9 and 57.7 +/- 39.7 ng/mL,
      respectively. CONCLUSION: Sexual dysfunction was less common in patients treated
      with quetiapine than with risperidone. Direct questioning about sexual
      functioning is necessary to avoid underestimating the frequency of sexual side
      effects in patients with schizophrenia and related psychotic disorders.

PMID- 14709949
TI  - A randomized evaluation of the effects of six antipsychotic agents on QTc, in the
      absence and presence of metabolic inhibition.
AB  - Many drugs have been associated with QTc prolongation and, in some cases, this is
      augmented by concomitant administration with metabolic inhibitors. The effects of
      6 antipsychotics on the QTc interval at and around the time of estimated peak
      plasma/serum concentrations in the absence and presence of metabolic inhibition
      were characterized in a prospective, randomized study in which patients with
      psychotic disorders reached steady-state on either haloperidol 15 mg/d (n = 27),
      thioridazine 300 mg/d (n = 30), ziprasidone 160 mg/d (n = 31), quetiapine 750
      mg/d (n = 27), olanzapine 20 mg/d (n = 24), or risperidone 6-8 mg/d increased to
      16 mg/d (n = 25/20). Electrocardiograms (ECGs) were done at estimated Cmax at
      steady-state on both antipsychotic monotherapy and after concomitant
      administration of appropriate cytochrome P-450 (CYP450) inhibitor(s). Mean QTc
      intervals did not exceed 500 milliseconds in any patient taking any of the
      antipsychotics studied, in the absence or presence of metabolic inhibition. The
      mean QTc interval change was greatest in the thioridazine group, both in the
      presence and absence of metabolic inhibition. The presence of metabolic
      inhibition did not significantly augment QTc prolongation associated with any
      agent. Each of the antipsychotics studied was associated with measurable QTc
      prolongation at steady-state peak plasma concentrations, which was not augmented
      by metabolic inhibition. The theoretical risk of cardiotoxicity associated with
      QTc prolongation should be balanced against the substantial clinical benefits
      associated with atypical antipsychotics and the likelihood of other toxicities.

PMID- 14709950
TI  - Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma
      clozapine concentrations: a predictive model and nomograms to aid clozapine dose
      adjustment and to assess compliance in individual patients.
AB  - The measurement of plasma clozapine concentrations is useful in assessing
      compliance, optimizing therapy, and minimizing toxicity. We measured plasma
      clozapine and norclozapine (N-desmethylclozapine) concentrations in samples from
      3782 patients (2648 male, 1127 female). No clozapine was detected in 291 samples
      (227 patients, median prescribed dose 300 mg/d). In 4963 (50.2 %) samples (2222
      patients); plasma clozapine concentration ranged from 10 to 350 ng/mL.Step-wise
      backward multiple regression analysis (37 % of the total samples) of log10 plasma
      clozapine concentration against log10 clozapine dose (mg/d), age (year), sex
      (male = 0, female = 1), cigarette smoking habit (nonsmokers = 0; smokers = 1),
      body weight (kg), and plasma clozapine/norclozapine ratio (clozapine metabolic
      ratio, MR) showed that these covariates explained 48% of the observed variation
      in plasma clozapine concentration (C = ng/mL x 10-3) (P < 0.001) according to the
      following equation: log 10 (C) = 0.811 log 10 (dose) + 0.332 (MR) + 69.42 X 10 (
      3) (sex) + 2.263 x 10 (-3) (age) + 1.976 x 10(-3) (weight) - 0.171 (smoking
      habit) - 3.180. This model and its associated confidence intervals were used to
      develop nomograms of plasma clozapine concentration versus dose for male and
      female smokers and nonsmokers. Predicted plasma clozapine changes by +48% in
      nonsmokers, +17% in females, +/-8 % for every 0.1 change in MR (reference 1.32),
      +/-4% for every 5 years (reference 40 years), and +/-5 % for every 10 kg body
      weight (reference 80 kg). The nomograms can be used (i) to individualize dosage
      to achieve a given target plasma clozapine concentration, and (ii) for
      quantitative evaluation of adherence by estimating the likelihood of an observed
      concentration being achieved by a given dosage regimen. The model has been
      validated against published data.

PMID- 14709954
TI  - Psychotropic prescribing for acute inpatient admissions in patients with severe
      psychosis.

PMID- 14709951
TI  - The effects of St. John's wort extract and amitriptyline on autonomic responses
      of blood vessels and sweat glands in healthy volunteers.
AB  - St. John's wort extract is widely used and advertised as a "natural
      antidepressant" lacking autonomic side effects. This randomized, double-blind,
      placebo-controlled study compared the effects of St. John's wort extract on
      autonomic responses of blood vessels and sweat glands with those of amitriptyline
      and placebo. A randomized, double-blind, crossover study was performed in healthy
      male volunteers aged 22 to 31 years (25 +/- 3 years; mean +/- SD) years. Subjects
      orally received capsules with 255 to 285 mg St. John's wort extract (900 microg
      hypericin content), 25 mg amitriptyline, and placebo 3 times daily for periods of
      14 days each with at least 14 days between. Vasoconstrictory response of
      cutaneous blood flow (VR) and skin conductance response (SR) following a single
      deep inspiration were employed as parameters of autonomic function. St. John's
      wort extract had no effect on VR and SR. In contrast, SR was diminished and the
      dilation phase of VR was prolonged following multiple dosing with amitriptyline
      (P < 0.05). Decreased electrodermal reactivity observed with amitriptyline
      reflects inhibition of acetylcholine at peripheral m3-cholinoreceptors, whereas
      prolongation of VR induced by the tricyclic drug may be due to sustained
      activation of central and/or peripheral sympathetic neurons.

PMID- 14709952
TI  - The effect of vitamin E treatment on tardive dyskinesia and blood superoxide
      dismutase: a double-blind placebo-controlled trial.
AB  - Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD).
      Vitamin E, a free radical scavenger, has been reported to improve symptoms of TD.
      The present study was designed to replicate this finding in a group of Chinese
      patients with TD, and to examine the effect of vitamin E treatment on blood
      superoxide dismutase (SOD), a critical enzyme in the detoxification of free
      radicals. Forty-one inpatients with TD completed a double-blind, placebo
      controlled, parallel-group study of vitamin E. Twenty-two of the patients were
      randomly assigned to receive a fixed dose of 1200 IU/d vitamin E, and 19 were
      assigned to a placebo for 12 weeks. Patients were assessed primarily using the
      Abnormal Involuntary Movement Scale (AIMS) at baseline, weeks 6 and 12. Blood SOD
      levels were measured by radioimmunometric assay before and after treatment. The
      results showed that the reduction in AIMS score from baseline was significantly
      higher with vitamin E treatment compared with placebo (45.9% vs. 4.3%). Blood SOD
      levels were significantly increased after treatment with vitamin E (P = 0.001),
      but no change with placebo treatment (P < 0.05). These results support earlier
      findings of the efficacy of vitamin E in the treatment of TD. Moreover, the
      efficacy of vitamin E may be due to its ability to increase SOD level, which may
      reduce oxidative injure in tardive dyskinesia.

PMID- 14709953
TI  - A prospective trial of modafinil as an adjunctive treatment of major depression.
AB  - Modafinil is a wake-promoting agent approved by the Federal Drug Administration
      for the treatment of narcolepsy. Preliminary evidence indicates that modafinil
      may improve fatigue and excessive sleepiness associated with a variety of
      conditions. The purpose of this study was to investigate the utility of modafinil
      as an adjunctive treatment of depressed patients. Subjects with a history of
      major depression with partial response on a stable therapeutic dose of an
      antidepressant were eligible to participate. All subjects endorsed complaints of
      significant fatigue and/or excessive sleepiness on clinical assessment. Modafinil
      was added to their existing regimen at a dose of 100 to 400 mg/d for 4 weeks.
      Subjects were assessed at 2-week intervals for improvement using the standard
      depression scales (HDRS, BDI, CGI), fatigue scales (VASF, FSI), and a
      neuropsychologic battery. Thirty-five subjects were entered and 31 subjects
      completed the 4-week trial. Significant improvements were seen across all 3
      measures of depression (HDRS, BDI, CGIS) and both measures of fatigue (VASF,
      FSI). On the neurocognitive battery, significant gains in the Stroop Interference
      Test were seen at 4 weeks, whereas the other cognitive tests showed no change.
      Modafinil may be a useful and a well-tolerated adjunctive agent to standard
      antidepressants in the treatment of major depression.

PMID- 14709957
TI  - Complete dopamine D2 receptor occupancy without extrapyramidal side effects under
      benperidol.

PMID- 14709956
TI  - Are high initial doses of olanzapine required to reduce agitation associated with
      schizophrenia?

PMID- 14709955
TI  - Olanzapine excretion into breast milk: a case report.

PMID- 14709960
TI  - Quetiapine for alcohol use and craving in bipolar disorder.

PMID- 14709959
TI  - Postmortem clozapine levels.

PMID- 14709961
TI  - Reply to article by Margolese and associates on tolerance and rebound during
      maintenance with quetiapine.

PMID- 14709958
TI  - Clozapine-induced sialorrhea treated with sublingual ipratropium spray: a case
      series.

PMID- 14709963
TI  - Carbamazepine-induced hypersensitivity syndrome, associated with human
      herpesvirus 6 reactivation.

PMID- 14709966
TI  - Zonisamide-induced depression and mania in patients with epilepsy.

PMID- 14709965
TI  - An open-label trial of bupropion in the treatment of pathologic gambling.

PMID- 14709967
TI  - More data for the CYP2D6 hypothesis?: the in vivo inhibition of CYP2D6 isoenzyme
      and extrapyramidal symptoms induced by antidepressants in the elderly.

PMID- 14709970
TI  - Sensitivity of median sensory nerve conduction tests in digital branches for the
      diagnosis of carpal tunnel syndrome.
AB  - OBJECTIVE: To compare the sensitivity of median sensory nerve conduction tests
      performed by stimulating digital branches in patients with carpal tunnel
      syndrome. DESIGN: A prospective study in 506 hands of patients with carpal tunnel
      syndrome diagnosed electrophysiologically. RESULTS: The sensitivity of median
      sensory nerve conduction tests across the first three digit-to-wrist segments and
      palm-to-wrist segment was determined. The most common abnormal electrophysiologic
      finding was the slowing of sensory nerve conduction velocity over the palm-to
      wrist segment, which was detected in 98.5% of the hands. Slowing of sensory nerve
      conduction velocity over the digit 1-, 2-, and 3-to-wrist segments of the median
      nerve was found in 95.4%, 88%, and 82% of the hands, respectively. CONCLUSION:
      The sensory nerve conduction velocity test of the digit 1-to-wrist segment has
      the most sensitivity among the three digital branches of the median sensory
      nerve, and it may be used more widely in the electrodiagnosis of carpal tunnel
      syndrome.

PMID- 14709968
TI  - Isokinetic performance after total hip replacement.
AB  - OBJECTIVE: To evaluate differences in isokinetic hip flexion, extension, and
      abduction muscle performance of operated vs. nonoperated hips in older adults who
      have undergone elective, unilateral, total hip replacement (THR) surgery and
      completed rehabilitation. DESIGN: Quasi-experimental study using a nonequivalent
      posttest-only control group design, comprising 20 unilateral THR patients and a
      convenience sample of 22 healthy older adults. THR patients participated between
      4 and 5 mos after surgery. THR subjects received an average of 13 outpatient or
      home-based physical therapy sessions. Isokinetic muscle strength and fatigue was
      assessed through measurement of hip peak torque per body weight, total work, and
      average power using a robotic dynamometer. RESULTS: Comparisons of THR subjects'
      operated vs. nonoperated hips showed no significant differences in isokinetic
      performance for any of the examined variables. THR subjects' operated hips
      generated significantly less peak torque per body weight, total work, and average
      power across all exercises as compared with a population of healthy subjects.
      CONCLUSIONS: THR subjects' operated and nonoperated hips showed similar
      biomechanical performance. THR patients are not being restored to the same level
      of strength and muscular endurance as compared with a population of healthy
      adults. These findings may be useful in providing a preliminary rationale for
      revising current approaches in THR rehabilitation protocols.

PMID- 14709969
TI  - Leg muscle activation patterns of sit-to-stand movement in stroke patients.
AB  - OBJECTIVE: To describe the characteristics of leg muscle activation patterns in
      hemiplegic stroke patients during the movement of rising from a chair and to
      determine the differences of leg muscle activation patterns between stroke
      fallers and nonfallers. DESIGN: Subjects stood up from an armless chair at a
      comfortable, self-paced speed. Leg muscle activation time and patterns during the
      sit-to-stand movement were analyzed using multichannel surface electromyography
      and a force platform. The differences between stroke fallers and nonfallers were
      compared. RESULTS: The mean onset time of muscle activity in the affected limbs
      of stroke fallers was markedly delayed for the tibialis anterior muscle and
      earlier for the soleus muscle. The muscle activation patterns in the affected
      side of the stroke fallers exhibited a wide range of variation. Seventy percent
      of our stroke fallers exhibited no or merely low-amplitude activity in their
      tibialis anterior muscle when the patients were rising from a chair. Half of the
      stroke fallers exhibited premature or excessive activation of their soleus muscle
      when the rising activity was initiated. CONCLUSIONS: Stroke patients who
      exhibited no or low-amplitude muscle activity in the tibialis anterior,
      associated with premature or excessive activation of the soleus muscle in their
      hemiplegic limbs, when rising from a chair were prone to falling. The
      compensatory excessive tibialis anterior and quadriceps muscle activation in the
      unaffected limbs of stroke patients might have a role in preventing them from
      falling.

PMID- 14709964
TI  - Valproate monotherapy in the treatment of civilian patients with non-combat
      related posttraumatic stress disorder: an open-label study.

PMID- 14709971
TI  - Effect of co-morbid traumatic brain injury on functional outcome of persons with
      spinal cord injuries.
AB  - OBJECTIVE: This study was undertaken to determine if persons who sustain a spinal
      cord injury (SCI) and co-morbid brain injury (dual diagnosis [DDS]) evidence
      smaller functional gains and experience significantly longer rehabilitation
      lengths of stay than persons with only an SCI. DESIGN: This retrospective
      comparison study was performed at a 100-bed rehabilitation hospital specializing
      in acute SCI and traumatic brain injury rehabilitation. Summary scale outcome
      data of persons who sustained an SCI were compared with outcome data of a group
      of persons with a DDS. Comparisons were established by matching groups
      principally on level of SCI and admission Motor FIM trade mark score and
      secondarily on education, sex, and age. Outcome measures included admission Motor
      and Cognitive FIM score, discharge Motor and Cognitive FIM score, Motor and
      Cognitive FIM change, length of stay, and rehabilitation charges. RESULTS:
      Persons with a DDS evidenced a significantly more impaired Cognitive FIM score at
      admission and discharge from rehabilitation. Persons with a DDS also achieved a
      significantly lower Motor FIM change than persons with SCI. There were no
      significant differences between DDS and SCI groups regarding Cognitive FIM
      change, length of stay, or rehabilitation charges. Injury severity as defined by
      the Glasgow Coma Scale or intracranial lesions did not predict response to
      treatment in the DDS group. CONCLUSION: Persons with a DDS achieved smaller
      functional gains during rehabilitation than peers with SCI. Brain injuries seem
      to limit functional gains, although the relationship between brain injury
      severity and functional change is not linear. Prospective studies are needed to
      identify factors limiting functional gains in rehabilitation and assist in
      developing specific treatment programs for persons with SCI and brain injury.

PMID- 14709972
TI  - Effect of shortened length of stay on functional and educational outcome after
      pediatric rehabilitation.
AB  - OBJECTIVE: The purpose of this study was to assess changes in the length of stay
      and its effect on effectiveness and return to school in an inpatient pediatric
      rehabilitation unit during a 5-yr period from fiscal year 1997 through 2001.
      DESIGN: We reviewed prospectively collected data for a cohort of 321 children
      during fiscal years 1997-2001. RESULTS: Length of stay was significantly
      shortened, with mean lengths of stay of 58.9, 43.5, 30.7, 40.9, and 24.0 days in
      years 1997 through 2001, respectively. Change in length of stay remained
      significantly decreased after adjusting for age, sex, admission diagnosis,
      admission severity, and type of health insurance. There was no difference in mean
      change in effectiveness measured by change in admission and discharge WeeFIM
      ratings. There were significant differences across years in the educational
      placement of children at discharge, with a declining trend in the proportion of
      children discharged to classroom-based educational services. CONCLUSION: There
      was a reduction in inpatient length of stay during a 5-yr period for children in
      this pediatric rehabilitation setting. During this time, there was no change in
      the effectiveness of rehabilitation as measured by functional outcome. However,
      using return to a classroom setting as a marker of reintegration into routine
      activities, fewer children returned to a similar level of community
      participation.

PMID- 14709973
TI  - Mechanical measurements of the effects of intrathecal baclofen dosage adjustments
      in cerebral palsy: a pilot study.
AB  - OBJECTIVE: The purpose of this pilot study was to determine the feasibility of
      using mechanical measures of stretch reflexes to monitor spasticity after
      intrathecal baclofen dosage changes. DESIGN: Mechanical measures were made in
      studying six participants with cerebral palsy who were undergoing treatment for
      spasticity using intrathecal baclofen therapy. Mechanical measurements of stretch
      reflexes were made before and after pump implant in four of the six participants
      and after dosage changes in all participants, for a period of up to 2 yrs. The
      measurements comprised electromyograms and resistive torque responses to movement
      of the ankle, imposed with an isokinetic dynamometer. For each test session,
      random movements were applied to the ankle at each of four to seven speeds,
      repeated three or five times. RESULTS: Stretch reflex excitability decreased in
      three of four participants after initiation of intrathecal baclofen therapy and
      decreased with increasing dosages in three of the six participants. Broken
      catheters coincided with heightened mechanical measures in two cases. CONCLUSION:
      Mechanical measures of stretch reflexes change after intrathecal baclofen dosage
      adjustments, reflecting the clinical course of intrathecal baclofen therapy.

PMID- 14709974
TI  - Botulinum neurotoxin type B and physical therapy in the treatment of piriformis
      syndrome: a dose-finding study.
AB  - OBJECTIVE: To measure dosage effects of botulinum neurotoxin type B with physical
      therapy in piriformis syndrome. DESIGN: Prospective study of consecutive patients
      complaining of buttock pain and sciatica, measuring serial H-reflex tests in
      flexion, adduction, and internal rotation; visual analog scale; and adverse
      effects at 0, 2, 4, 8, and 12 wks. We used an electrophysiologic criterion for
      piriformis syndrome: a 1.86-msec prolongation of the H-reflex with the flexion,
      adduction, and internal rotation test. Four piriformis syndrome groups were
      identified. Serial groups were injected once with either 5000, 7500, 10,000, or
      12,500 units of botulinum neurotoxin type B in successive months under
      electromyographic guidance in four separate locations of the affected piriformis
      muscle, with a 1-mo safety observation period between groups. Patients received
      physical therapy twice weekly for 3 mos. RESULTS: The flexion, adduction, and
      internal rotation test and visual analog scale declined significantly,
      correlating at 72% sensitivity and 77% specificity. A total of 24 of 27 study
      patients had >/=50% pain relief. Mean visual analog scale score declined from 6.7
      to 2.3. A volume of 12,500 units of botulinum neurotoxin type B was superior to
      10,000 units at 2 wks postinjection. The most severe adverse effects were dry
      mouth and dysphagia, approaching 50% of patients at 2 and 4 wks. CONCLUSION:
      Physical therapy and 12,500 units of botulinum neurotoxin type B seem to be safe
      and effective treatment for piriformis syndrome. In addition, the flexion,
      adduction, and internal rotation test seems to be an effective means of
      diagnosing piriformis syndrome and assessing its clinical improvement. Injection
      may benefit patients for >3 mos.

PMID- 14709975
TI  - Technical standards for the education of physicians with physical disabilities:
      perspectives of medical students, residents, and attending physicians.
AB  - OBJECTIVE: This pilot study assessed the opinions of medical students, residents,
      and attending physicians regarding the technical standards for medical school
      admission and the competencies required of graduates in the context of physical
      disability issues. DESIGN: Students, residents, and faculty from all specialties
      at a major academic medical center were surveyed regarding the concept of the
      "undifferentiated graduate;" the relative importance of motor, sensory,
      observation, and communication skills; the importance of specific technical
      skills; and the use of physician extenders and other accommodations to fulfill
      technical standards. RESULTS: Respondents placed higher importance on observation
      and communication skills compared with motor skills. Of respondents, 69.8% either
      disagree or strongly disagree with the idea that a medical student should be an
      undifferentiated candidate possessing all the technical skills necessary to enter
      any specialty. CONCLUSIONS: Technical skills used in interpretation and
      observation were more important to respondents than those technical skills that
      are purely procedural. Respondents largely rejected the concept of the
      undifferentiated graduate. Although statistical analyses are of limited
      reliability because of low response rates, this study represents the most
      extensive sampling to date of medical professionals' opinions on these issues.
      Respondents' narrative comments also provided valuable perspectives.

PMID- 14709976
TI  - Autonomic dysreflexia after intramuscular injection in traumatic tetraplegia: a
      case report.
AB  - Autonomic dysreflexia is a syndrome of massive imbalance of reflex sympathetic
      discharge occurring in patients with spinal cord lesion above the splanchnic
      outflow (T6). It is characterized by a sudden onset and severe increase in blood
      pressure and is potentially life threatening. The most common causes are bladder
      and rectum distention. In this case study, we report an autonomic dysreflexia
      case that developed after intramuscular injection in a 29-yr-old tetraplegic
      patient with C5 American Spinal Injury Association grade A lesion. After careful
      scrutiny of English literature, this clinical manifestation seems to be an
      unusual event.

PMID- 14709977
TI  - Refeeding syndrome: implications for the inpatient rehabilitation unit.
AB  - Patients admitted to inpatient rehabilitation units commonly have underlying
      medical disorders and are at risk for poor oral intake and malnutrition, which
      may be compounded by dysphagia and anorexia. The refeeding syndrome is an
      underappreciated but clinically important entity characterized by acute
      electrolyte abnormalities, fluid retention, and dysfunction of various organ
      systems, which can result in significant morbidity and, occasionally, death.
      Reinstitution of nutrition by any route in a undernourished patient may lead to
      acute electrolyte shifts and fluid retention, which are hallmarks of the
      refeeding syndrome. As such, this article briefly summarizes the clinical
      manifestations and treatment of refeeding syndrome as it relates to patients
      admitted to the inpatient rehabilitation unit.

PMID- 14709978
TI  - Linguistic and gait disturbance in a child with Laurence-Moon-Biedl syndrome:
      left temporal and parietal lobe hypoplasia.
AB  - Laurence-Moon-Biedl syndrome is an autosomal recessive disorder characterized by
      retinitis pigmentosa, obesity, polydactyly, hypogenitalism, mental retardation,
      and renal abnormalities. We report the linguistic and gait disorders in a child
      with Laurence-Moon-Biedl syndrome associated with left temporal and parietal
      hypoplasia as determined by magnetic resonance imaging. Our patient was mildly
      mentally retarded, scoring better on the performance subtest than on the verbal
      subtest. He received serial assessments for developmental, language, speech, and
      gait functions, before and after rehabilitation, at age 4.5 and 6 yr,
      respectively. After comprehensive rehabilitation, the boy achieved improvement in
      speech, language, fine motor, and gait functions. Early comprehensive
      rehabilitation programs seem beneficial for improving functional development for
      children with Laurence-Moon-Biedl syndrome.

PMID- 14709979
TI  - Pertinacious habit on a rehabilitation unit: repetitive finger licking while
      paging through the clinical chart.
AB  - A survey was performed to determine the frequency of unrecognized repetitive
      licking of fingers while reviewing hospital charts by various healthcare
      professionals who, by this habit, may be putting themselves at risk of acquiring
      a nosocomial infection. Nine of 14 charts demonstrated the presence of
      Staphylococci aureus, cultures obtained from three of nine charts grew
      methicillin-resistant S. aureus, and six grew methicillin-susceptible S. aureus.
      Of the 50 healthcare professionals surveyed, five (10%) admitted to habitual
      repetitive licking of fingers while reviewing charts. In addition, 30 (60%) of
      those surveyed had observed other professionals doing so. Forty-seven (94%)
      acknowledged that they did not routinely wash their hands after reviewing the
      charts, potentially placing themselves at risk of acquiring a nosocomial
      infection. As an immediate consequence of this study, staff members have been
      encouraged to wash their hands before and after reviewing a patient's chart.

PMID- 14709980
TI  - Injury in a throwing athlete: understanding the kinetic chain.

PMID- 14709983
TI  - Efficacy of pediatric-specific trauma centers.

PMID- 14709984
TI  - Pharmacologic therapy for persistent pulmonary hypertension of the newborn: as
      "poly" as the disease itself.

PMID- 14709985
TI  - How much energy must we spend to assess the energy expenditure in the critically
      ill pediatric patient?

PMID- 14709988
TI  - The application of sentinel node radiolocalization to solid tumors of the head
      and neck: a 10-year experience.
AB  - OBJECTIVES/HYPOTHESIS: The goals of the research study were to develop an easily
      mastered, accurate, minimally invasive technique of sentinel node
      radiolocalization with biopsy (SNRLB) in the feline model; to compare it with
      blue-dye mapping techniques; and to test the applicability of sentinel node
      radiolocalization biopsy in three head and neck tumor types: N0 malignant
      melanoma, N0 Merkel cell carcinoma, and N0 squamous cell carcinoma. STUDY DESIGN:
      Prospective consecutive series studies were performed in the feline model and in
      three head and neck tumor types: N0 malignant melanoma (43 patients), N0 Merkel
      cell carcinoma (8 patients), and N0 squamous cell carcinoma (20 patients).
      METHODS: The technique of sentinel node radiolocalization with biopsy was
      analyzed in eight felines and compared with blue-dye mapping. Patterns of
      sentinel node gamma emissions were recorded. Localization success rates were
      determined for blue dye and sentinel node with radiolocalization biopsy. In the
      human studies, all patients had sentinel node radiolocalization biopsy performed
      in a similar manner. On the morning of surgery, each patient had sentinel node
      radiolocalization biopsy of the sentinel lymph node performed using an
      intradermal or peritumoral injection of technetium Tc 99m sulfur colloid.
      Sentinel nodes were localized on the skin surface using a handheld gamma
      detector. Gamma count measurements were obtained for the following: 1) the "hot"
      spot/node in vivo before incision, 2) the hot spot/node in vivo during
      dissection, 3) the hot spot/node ex vivo, 4) the lymphatic bed after hot
      spot/node removal, and 5) the background in the operating room. The first
      draining lymph node(s) was identified, and biopsy of the node was performed. The
      radioactive sentinel lymph node(s) was submitted separately for routine
      histopathological evaluation. Preoperative lymphoscintigrams were performed in
      patients with melanoma and patients with Merkel cell carcinoma. In patients with
      head and neck squamous cell carcinoma, the relationship between the sentinel node
      and the remaining lymphatic basin was studied and all patients received complete
      neck dissections. The accuracy of sentinel node radiolocalization with biopsy,
      the micrometastatic rate, the false-negative rate, and long-term recurrence rates
      were reported for each of the head and neck tumor types. In the melanoma study,
      the success of sentinel node localization was compared for sentinel node
      radiolocalization biopsy, blue-dye mapping, and lymphoscintigraphy. In the Merkel
      cell carcinoma study, localization rates were evaluated for sentinel node
      radiolocalization biopsy and lymphoscintigraphy. In the head and neck squamous
      cell carcinoma study, the localization rate of sentinel node radiolocalization
      biopsy and the predictive value of the sentinel node relative to the remaining
      lymphatic bed were determined. All results were analyzed statistically. RESULTS:
      Across the different head and neck tumor types studied, sentinel node
      radiolocalization biopsy had a success rate approaching 95%. Sentinel node
      radiolocalization biopsy was more successful than blue-dye mapping or
      lymphoscintigraphy at identifying the sentinel node, although all three
      techniques were complementary. There was no instance of a sentinel node-negative
      patient developing regional lymphatic recurrence. In the head and neck squamous
      cell carcinoma study, there was no instance in which the sentinel node was
      negative and the remaining lymphadenectomy specimen was positive. CONCLUSION: In
      head and neck tumors that spread via the lymphatics, it appears that sentinel
      node radiolocalization biopsy can be performed with a high success rate. This
      technique has a low false-negative rate and can be performed through a small
      incision. In head and neck squamous cell carcinoma, the histological appearance
      of the sentinel node does appear to reflect the regional nodal status of the
      patient.

PMID- 14709989
TI  - Management of neck metastasis with carotid artery involvement.
AB  - OBJECTIVES: To demonstrate aggressive management of neck metastasis adherent to
      the internal or common carotid artery using sound oncologic principles while
      minimizing the significant risk of complications. STUDY DESIGN: Our 13 year
      experience of treating patients with recurrent or residual neck metastasis
      adherent to the internal or common carotid artery was retrospectively reviewed.
      METHODS: Angiography was used in patients who demonstrated fixation of the
      carotid artery on examination or imaging, followed by balloon test occlusion and
      single photon emission computer tomography (SPECT) scanning. The majority of
      carotid resections were reconstructed with a vein graft, especially if there was
      insufficient collateral cerebral circulation. Radical resection of the soft
      tissue including the carotid artery was performed followed by 15 to 20 Gray of
      electron beam delivered directly to the deep tissue. More recently, the carotid
      has been permanently occluded preoperatively, if possible. The assessment of the
      cerebral circulation and management of the carotid artery were analyzed as was
      survival, site of recurrence, and complications. RESULTS: Fifty-eight charts were
      reviewed. The majority of patients (41) had their carotid artery reconstructed at
      time of resection, and the remaining had either the artery ligated or permanently
      occluded preoperatively. Strokes occurred in 11 patients. The median disease
      specific survival was 12 months, with 24% of patients dying from distant
      metastasis. CONCLUSIONS: The high risk of complications, loss of life's quality,
      and mortality must be balanced against the natural history of the disease if left
      untreated. The decision is a heavy burden for the patient, family, and head and
      neck surgeon.

PMID- 14709990
TI  - Meningioma of the jugular foramen: glomus jugulare mimic and surgical challenge.
AB  - OBJECTIVES: Meningiomas involving the jugular foramen are rare lesions, with
      approximately 34 cases reported in the English literature. Clinically, these
      tumors mimic the more common glomus jugulare tumor. After surgical resection,
      meningiomas have worse cranial nerve outcomes and higher recurrence rates than
      glomus tumors. There is controversy regarding the selection of surgical approach,
      particularly with regard to management of the facial nerve. A reliable means of
      accurate preoperative diagnosis would help surgical planning and patient
      counseling. STUDY DESIGN: We present a series of six consecutive large jugular
      foramen meningiomas resected by a single surgeon from 1996 to 2002. METHODS:
      Retrospective case series (chart review). RESULTS: The preoperative diagnosis was
      correct in nearly all (6/7) cases on the basis of the characteristic imaging
      findings seen with a combination of temporal bone dedicated computed tomography
      and high-resolution enhanced magnetic resonance imaging. Five of six patients had
      lateral facial nerve rerouting (infratemporal fossa Fisch type A), and three
      patients also had posterior rerouting (transcochlear approach with division of
      greater superficial petrosal nerve). Total tumor removal was accomplished in 83%.
      One patient suffered recurrence over a mean follow-up period of 2.5 years. New
      postoperative vocal cord palsies occurred in 50% of patients, and all required
      vocal cord medialization. At 1 year, 50% of patients had normal or near normal
      (House-Brackmann I or II) facial function. Postoperative cerebrospinal fluid
      leaks occurred in two patients, and both eventually required ventriculoperitoneal
      shunts. CONCLUSIONS: Meningiomas involving the jugular foramen are surgically
      challenging tumors that pose unique diagnostic issues. The majority of these
      lesions can be completely resected. A relatively high postoperative complication
      rate, which can be controlled with appropriate intervention, is seen with these
      surgeries.

PMID- 14709991
TI  - Hydroxyapatite cement in temporal bone surgery: a 10 year experience.
AB  - OBJECTIVES: To describe the indications for successful use of hydroxyapatite
      cement (HAC) in temporal bone surgery. STUDY DESIGN: Retrospective case review.
      METHODS: One hundred nine temporal bone defects related to surgical approaches to
      the skull base, infection, neoplasms, or congenital defect in 102 adults and
      children were corrected using HAC over a 10-year period. The results and
      complications were obtained through retrospective chart review. RESULTS: Ninety
      seven percent of temporal bone defects were successfully repaired using HAC, and
      the reconstruction remained stable over the course of this study. There was one
      case of postoperative cerebrospinal fluid leak. Wound infection occurred in three
      patients, which required reoperation and removal of the biomaterial. CONCLUSIONS:
      HAC is a biomaterial that should be used as the primary method to reconstruct
      temporal bone defects. Proper use of this biomaterial results in restoration of
      the integrity of the temporal bone and elimination of cerebrospinal fluid leak as
      a postoperative complication.

PMID- 14709992
TI  - Tissue-engineered human nasal septal cartilage using the alginate-recovered
      chondrocyte method.
AB  - OBJECTIVES: Tissue engineering of nasal septal cartilage has numerous potential
      applications in craniofacial reconstruction. Chondrocytes suspended in alginate
      gel have been shown to produce a substantial cell-associated matrix. The
      objective of this study was to determine whether cartilage tissue could be
      generated using the alginate-recovered-chondrocyte (ARC) method, in which
      chondrocytes are cultured in alginate as an intermediate step in tissue
      fabrication. METHODS: Nasal septal chondrocytes from five patient donors were
      isolated by enzymatic digestion, then expanded in monolayer culture. At
      confluency, a portion of those cells were seeded at high density onto a
      semipermeable membrane and cultured for 14, 21, or 28 days (monolayer group). The
      remaining cells were suspended in alginate and cultured until a cell-associated
      matrix was observed (10-17 days). Cells and their associated matrix were released
      from alginate (ARC group), seeded onto a semipermeable membrane, and cultured as
      already described. DNA (Hoechst 33258 Assay), glycosaminoglycan (GAG;
      dimethylmethylene blue assay), and collagen (hydroxyproline assay) were analyzed
      biochemically. Immunohistochemistry was performed to assess expression of
      collagens type I and type II. Histochemistry was performed to localize cells
      accumulating sulfated GAG (Alcian blue stain). RESULTS: The ARC constructs, in
      contrast to the monolayer constructs, had substantial structural stability and
      the histologic and gross appearance of cartilaginous tissue. ARC constructs
      demonstrated significantly greater GAG and collagen accumulation than monolayer
      constructs (P <.05). Histologic analysis revealed substantial GAG and collagen
      type II production and only moderate collagen type I production. The composition
      of the matrix was thus similar to that of native human septal cartilage.
      CONCLUSIONS: Tissue-engineered human nasal septal cartilage using the ARC method
      has the histologic and gross appearance of native cartilage and has biochemical
      composition more like that of native cartilage than monolayer constructs. This is
      the first report of human nasal septal neocartilage formation without the use of
      biodegradable scaffolds.

PMID- 14709993
TI  - The effects of the plasminogen pathway on scar tissue formation.
AB  - OBJECTIVES/HYPOTHESIS: The authors sought to determine the role of the
      plasminogen pathway in wound healing. They hypothesized that decreased fibrin
      degradation may lead to increased collagen deposition. Presuming that the degree
      of histopathological abnormality correlates with the aesthetic appearance of the
      scar, we conducted a study that attempted to determine the histopathological
      appearance of scar tissue in mice with and without impaired function of the
      plasminogen pathway. STUDY DESIGN: Mice with and without deficiencies in the
      plasminogen pathway underwent surgery. The role of the plasminogen pathway in
      wound healing was studied by analysis of scar tissue formation using the methods
      described. METHODS: A 2-cm incision was made on the dorsum of mice with and
      without specified genetic deficiencies in the plasminogen pathway. After the
      animals were killed, the tissue was harvested, fixed, and prepared using
      hematoxylin and eosin as well as trichrome stains. Histopathological analysis and
      scoring were performed by two separate investigators in a blinded manner.
      Student's t test was used to determine statistical significance between groups.
      RESULTS: A statistically significant difference in collagen orientation was noted
      between mice with impaired plasminogen pathway function and the wild-type
      (control) group (P =.0163). A statistical trend toward improved wound healing for
      plasminogen-deficient mice was found for overall histomorphological score (P
      =.0706). CONCLUSION: The role of the plasminogen pathway in wound healing is one
      that should be noted and may lead to the development of new therapies that reduce
      scar tissue formation. Hence, the role of other thrombolytic and anti
      thrombolytic agents in wound healing should be further investigated to precisely
      identify agents that play the most significant role in scar tissue formation.

PMID- 14709994
TI  - Time scale for periosteal readhesion after brow lift.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to determine the time interval after
      brow lift required to achieve periosteal readhesion to the skull with
      preoperative strength [corrected]. STUDY DESIGN: Randomized prospective analysis
      of variance with repeated measures. METHODS: Twenty-one New Zealand white
      rabbits, each serving as its own control, underwent subperiosteal elevation on
      one side of the skull. The elevated periosteum was lifted and fixed to a
      resorbable screw, and the contralateral periosteum was left untouched. Adhesion
      characteristics were subsequently examined at postoperative days 5, 6, 7, 8, 10,
      12, and 17. Seven subjects were assessed histologically to determine attachment
      of periosteum to underlying bone. Fourteen subjects underwent biomechanical
      analysis of the bone-periosteum interface using the following three measures of
      periosteal readhesion strength: ultimate shear strength, shear stiffness, and
      shear energy [corrected]. RESULTS: Blinded histological analysis showed a
      qualitative increase in the number of markers of periosteal healing on days 8 to
      12 for the operated sides. Analysis of ultimate shear strength and shear
      stiffness demonstrated a significant relationship to postoperative day (P <.001).
      The ultimate shear strength and shear stiffness of the operated side approached
      that of the nonoperated side by postoperative days 12 and 8, respectively. Shear
      energy was significantly lower for all time points on the operated side as
      compared with the control (P <.02). CONCLUSION: Periosteal readhesion after
      surgical elevation approaches preoperative strength by the twelfth postoperative
      day.

PMID- 14709996
TI  - Ossicular reconstruction with titanium prosthesis.
AB  - OBJECTIVES: To evaluate the results when using titanium total ossicular
      replacement prosthesis (TORP) or partial ossicular replacement prosthesis (PORP)
      in chronic ear disease. STUDY DESIGN: Retrospective chart review was performed.
      METHODS: Sixty-eight ossicular procedures using a titanium TORP (n = 30) or PORP
      (n = 38) were performed at a tertiary referral center between December 1999 and
      June 2002. The ossiculoplasty was performed either alone or in combination with
      other chronic ear surgery. Cartilage grafts were used universally. Nineteen
      percent were primary operations, and 6% were planned second stages. The majority
      were revision procedures. Follow-up ranged from 3 months to 2.5 years. RESULTS:
      The prosthesis is easy to insert, well tolerated, and has a low extrusion rate.
      Average air-bone gap (ABG) improvement was 13 dB with closure of the ABG to
      within 20 dB in 57% of cases. Hearing results were better for primary versus
      revision cases for PORPs versus TORPs and for intact canal wall (ICW) procedures
      versus canal wall-down (CWD) procedures. CONCLUSION: Titanium is a satisfactory
      material for use in ossicular reconstruction because of its ease of insertion,
      tissue tolerance, and low rate of extrusion. Caution is advised when selecting
      candidates for this procedure during revision surgery, especially if the canal
      wall and stapes superstructure are absent.

PMID- 14709995
TI  - Internal jugular vein thrombosis and deep neck infection from intravenous drug
      use: management strategy.
AB  - OBJECTIVE: Internal jugular vein thrombosis (IJVT) manifests in multiple clinical
      scenarios including traumatic, neoplastic, and infectious processes. No clear
      management algorithm exists for IJVT in the setting of deep neck infections. This
      study examines the cause, diagnosis, and treatment strategy for IJVT in the
      setting of deep neck infections caused by intravenous drug use (IVDU). STUDY
      DESIGN: Retrospective chart review. METHODS: The clinical, radiographic, and
      laboratory data of 11 IVDU patients with deep neck infections and IJVT are
      reviewed in a retrospective fashion. The patients were seen in a university
      tertiary care facility. RESULTS: Eleven patients with deep neck infections,
      recent history of IVDU, and concurrent IJVT were identified. All patients
      underwent computed tomography (CT) scanning. Antibiotic therapy was instituted in
      all cases, abscesses were treated invasively with aspiration or incision and
      drainage, and no veins were ligated or resected. Three patients received
      anticoagulation. One patient had bilateral IJVT with thrombus extension through
      the sigmoid sinus to the lateral sinus. This patient received anticoagulation and
      developed bacteremia. No further IJVT complications have been diagnosed at an
      average of 14 months postintervention. CONCLUSION: IJVT and deep neck infection
      caused by IVDU constitute a clinical entity present even in the modern day era of
      antibiotic therapy. Aggressive antibiotic therapy and surgical intervention for
      the deep neck infection is recommended. The indications for anticoagulation
      remain variable. Although anticoagulation is often recommended in the presence of
      thrombus progression or septic emboli, the very presence of IJVT does not mandate
      the need for anticoagulation. Ligation or resection of the thrombosed vein may be
      reserved for selected cases, but was not necessary in our series.

PMID- 14709997
TI  - Results with titanium ossicular reconstruction prostheses.
AB  - OBJECTIVES/HYPOTHESIS: Despite the enthusiasm of recent short-term reviews, no
      center in the United States has published results meeting American Academy of
      Otolaryngology-Head and Neck Surgery guidelines with titanium-based prostheses.
      The purpose of the study was threefold. The first purpose was to review results
      with a titanium prosthesis system in cases meeting American Academy of
      Otolaryngology-Head and Neck Surgery reporting guidelines. The second was to
      compare these results with previously published results using non-titanium-based
      prostheses. The third was to examine the authors' results for any evidence of a
      "learning curve." STUDY DESIGN: Retrospective chart review was performed for the
      period from February 2000 to August 2001 and for the period from July 2002 to
      February 2003. METHODS: Of 313 cases, 130 consecutive cases were identified in
      the first period and 65 in the second time period. One hundred two patients had
      adequate follow-up for published guidelines. All cases were performed by the
      senior author (c.g.j.). Comparison data were obtained from a previous publication
      involving the senior author. RESULTS: Successful rehabilitation (<or=20 dB pure
      tone average air-bone gap) of conductive hearing loss was obtained in 70% of
      partial ossicular chain reconstructions and 44% of total ossicular chain
      reconstructions when titanium prostheses were used. Comparison data revealed
      successful rehabilitation in 48% and 21% of non-titanium-based partial and total
      reconstructions, respectively. Postoperative pure-tone average air-bone gaps were
      not significantly different when compared with results in the period from July
      2002 to February 2003. CONCLUSION: Newer titanium-based ossicular reconstruction
      devices represent an improvement over previously used non-titanium-based
      prostheses. The authors think that this improvement is realized rapidly because
      no learning curve existed in their data.

PMID- 14709998
TI  - Electrophysiologic effects of placing cochlear implant electrodes in a
      perimodiolar position in young children.
AB  - OBJECTIVE: The purpose of this study was to intraoperatively record the
      electrically evoked auditory brainstem response (EABR) before and after placement
      of the electrode positioning system (EPS) (CII Bionic Ear with HiFocus I cochlear
      implant electrode array) as well as before and after stylet removal (Nucleus
      Contour cochlear implant electrode array). It was hypothesized that physiologic
      changes would occur after perimodiolar positioning of the electrode array and
      these changes would be evident from the EABR recordings. STUDY DESIGN:
      Consecutive young (11-36 month old) pediatric cochlear implant recipients (n =
      17) had intraoperative EABRs recorded from three intracochlear electrodes that
      represented apical, medial, and basal locations. Wave V amplitudes and thresholds
      were studied relative to electrode location and pre- versus postperimodiolar
      positioning. These evoked potential measures were analyzed for statistical
      significance. SETTING: Tertiary referral children's hospital/medical college.
      RESULTS: Wave V thresholds of the EABR were lower, and amplitudes were larger
      after perimodiolar positioning, although the changes were dependent on electrode
      location and implant design. Statistically significant decreases in EABR wave V
      threshold and increases in suprathreshold wave V amplitude were found for the
      basal electrode for the CII Bionic Ear HiFocus I and for the apical electrode for
      the Nucleus Contour. CONCLUSIONS: Placement of either the CII Bionic Ear HiFocus
      I or Nucleus Contour cochlear implant electrode array in the perimodiolar
      position in young children resulted in less electrical current necessary to
      stimulate the auditory system. Changes in electrophysiologic thresholds and
      amplitudes, measured with EABR, indicate that the electrode array is placed
      closer to the modiolus with both electrode designs.

PMID- 14709999
TI  - Bilateral bone-anchored hearing aids (BAHAs): an audiometric evaluation.
AB  - OBJECTIVES: Since the technique to implant bone-anchored hearing aids (BAHAs)
      with the use of osseointegrated implants was developed in 1977, more than 15,000
      patients have been fitted with BAHAs worldwide. Although the majority have
      bilateral hearing loss, they are primarily fitted unilaterally. The main
      objective of this study was to reveal benefits and drawbacks of bilateral fitting
      of BAHAs in patients with symmetric or slight asymmetric bone-conduction
      thresholds. The possible effects were divided into three categories: hearing
      thresholds, directional hearing, and binaural hearing. STUDY DESIGN: Prospective
      study of 12 patients with bilateral BAHAs. METHODS: Baseline audiometry,
      directional hearing, speech reception thresholds in quiet and in noise, and
      binaural masking level difference were tested when BAHAs were fitted unilaterally
      and bilaterally. RESULTS: Eleven of the 12 patients used bilateral BAHAs on a
      daily basis. Tests performed in the study show a significant improvement in sound
      localization with bilateral BAHAs; the results with unilateral fitting were close
      to the chance level. Furthermore, with bilateral application, the improvement of
      the speech reception threshold in quiet was 5.4 dB. An improvement with bilateral
      fitting was also found for speech reception in noise. CONCLUSIONS: Overall, the
      results with bilateral fitted BAHAs were better than with unilaterally fitted
      BAHA; the benefit is not only caused simply by bilateral stimulation but also, to
      some extent, by binaural hearing. Bilateral BAHAs should be considered for
      patients with bilateral hearing loss otherwise suitable for BAHAs.

PMID- 14710000
TI  - Comparison of free radicals and antioxidant enzymes in chronic otitis media with
      and without tympanosclerosis.
AB  - OBJECTIVE/HYPOTHESIS: The pathogenesis of tympanosclerosis is unclear. The study
      was performed to investigate the role of nitric oxide, free oxygen radicals, and
      antioxidants in development of tympanosclerosis in patients with chronic otitis
      media. STUDY DESIGN: A prospective study in patients with nasal polyps. METHODS:
      Sixty-five patients who underwent tympanoplasty or tympanoplasty together with
      mastoidectomy were included in the study. Preoperative venous blood samples were
      drawn, and serum sodium, potassium, calcium, alkaline phosphatase, inorganic
      phosphorus, parathormone, and calcitonin levels were measured. The patients who
      had tympanosclerotic plaques on tympanic membrane or middle ear mucosa or near
      the ossicular chain or mastoid bone were designated as group 1 (n = 34), and the
      remaining patients as group 2 (n = 31). Intraoperatively, specimens were obtained
      from the middle ear mucosa and tympanic membrane to measure nitric oxide and
      malondialdehyde levels. In addition, plasma malondialdehyde levels and
      erythrocyte superoxide dismutase and catalase activity were determined. RESULTS:
      All patients had similar demographic features and serum electrolyte and hormone
      levels. Nitric oxide and malondialdehyde levels of the specimens obtained from
      the middle ear mucosa (P =.001) and tympanic membrane (P =.01) and, in parallel
      to this, the plasma malondialdehyde activity level were higher in group 1 than in
      group 2. Moreover, group 2 had significantly lower erythrocyte catalase activity
      levels (P =.001) compared with group 1, whereas such a significant difference was
      not present for superoxide dismutase activity levels (P >.05). CONCLUSION: The
      study results suggest that nitric oxide, free oxygen radicals, and catalase may
      have a role in the development of tympanosclerosis in patients with chronic
      otitis media.

PMID- 14710001
TI  - Prothrombotic factors in children with otitis media and sinus thrombosis.
AB  - OBJECTIVE: Venous sinus thrombosis (VST) is the second most common intracranial
      complication of acute otitis media (AOM). There is some evidence that hereditary
      and acquired prothrombotic disorders are risk factors for VST. The aim of the
      present study was to evaluate whether children with AOM complicated VST have a
      prothrombotic tendency, which might have important therapeutic and preventive
      implications. STUDY DESIGN: Retrospective. METHODS: The files of children
      hospitalized at Schneider Children's Medical Center of Israel, a tertiary
      referral center, from 1999 to 2002, because of AOM complicated by acute
      mastoiditis and VST were reviewed. All children underwent laboratory work-up for
      hypercoagulability. RESULTS: Seven children met the study criteria. Of these,
      five had prothrombotic disorders, namely elevated levels of lipoprotein
      apolipoprotein (Lp[a]) (n = 4), antibodies to beta 2-glycoprotein and to
      cardiolipin (markers of antiphospholipid syndrome) (n = 4), and heterozygosity
      for factor V Leiden mutation (n = 1). One child had three abnormalities, two
      children had two abnormalities, and two children had one abnormality.
      CONCLUSIONS: A prothrombotic tendency may exist in children with AOM complicated
      by mastoiditis and VST. Further studies are needed to evaluate its extent.

PMID- 14710002
TI  - Functional magnetic resonance imaging of activation in subcortical auditory
      pathway.
AB  - OBJECTIVES: Functional magnetic resonance imaging (fMRI) has been used to
      investigate activation of the auditory cortex; however, assessment of activation
      in the subcortical auditory pathway has been challenging. The aim of this study
      was to examine neural correlates of cortical and subcortical auditory activation
      evoked by pure-tone stimulus using silent fMRI. STUDY DESIGN: Prospective
      analysis. METHODS: Seventeen normal-hearing volunteers (7 male, 10 female; age
      range, 14-37 yrs) underwent silent fMRI. An audiometer was used to deliver pure
      tones of 1000 Hz to the left ear. Pure tones were presented at hearing thresholds
      determined in the scanner. Brain regions showing increased activation during pure
      tone stimulus presentation were mapped and auditory activations exceeding P <.001
      were included in the analysis. RESULTS: Pure-tone stimuli evoked bilateral
      activation in cortical regions of the transverse and superior temporal gyri and
      the planum temporale. Activation in subcortical structures included the medial
      geniculate body, inferior colliculus, lateral lemniscus, superior olivary
      complex, and cochlear nucleus. CONCLUSIONS: Silent functional magnetic resonance
      imaging findings documented the feasibility of detecting activation elicited by
      pure tone along the cortical and subcortical auditory pathway. The use of this
      technique in the assessment of disorders with auditory dysfunction merits further
      investigation.

PMID- 14710003
TI  - Long-term results after interval therapy with intratympanic gentamicin for
      Meniere's disease.
AB  - OBJECTIVES: The new single-shot and interval treatment for Meniere's disease with
      gentamicin was designed to avoid cochlear damage during treatment with
      gentamicin. METHODS: To date, 90 patients were treated with the single-shot or
      interval gentamicin therapy. Fifty-seven cases of Meniere's disease were followed
      up prospectively between 2 and 4 years. During one treatment series, a maximum of
      three intratympanic gentamicin injections within 15 days were applied, each
      consisting of 0.3 mL (12 mg) of gentamicin (days 1, 8, and 15). Thirty of these
      57 patients (53%) needed only one injection to be controlled (single-shot
      treatment). RESULTS: Vertigo attacks were completely controlled in 95% and
      partially controlled in 5%, whereas hearing remained unchanged or even improved.
      Tinnitus as well as aural fullness were controlled in approximately 50% of the
      cases. CONCLUSION: Our results with this group of patients after interval
      treatment or single-shot application of intratympanic gentamicin demonstrate the
      effectiveness of this treatment modality with very low side effects, and,
      although our experience is still limited, it allows for expanding the indication
      on early cases of Meniere's disease before permanent hearing loss occurs. Even
      cases of bilateral Meniere's disease can be treated successfully using this
      method. Cochleotoxic side effects can be prevented by treatment intervals of 7
      days.

PMID- 14710004
TI  - Endoscopic surgery for recurrent inverted papilloma.
AB  - OBJECTIVES/HYPOTHESIS: Inverted papilloma of the nose and paranasal sinuses is
      noted for its high rate of recurrence. The feasibility of endoscopic treatment
      for inverted papilloma has been shown in the literature; however, reports
      discussing the efficacy of endoscopic surgery for recurrent diseases are rare.
      The study determined the effectiveness of endoscopic surgery for recurrent
      inverted papilloma and described when endoscopic medial maxillectomy was
      indicated. STUDY DESIGN: Retrospective. METHODS: Seventeen patients with
      recurrent inverted papilloma were treated over a 10-year period. Krouse's staging
      system was used for tumor grading. Because of the extent of the tumor in the
      majority (70.6%) of the patients, en bloc resection could not be regularly
      achieved; therefore, sequential segmental endoscopic surgery was the chosen
      treatment. Some diseases that extensively involved the maxillary sinus were
      treated by the combination of endoscopic medial maxillectomy (EMM) and sequential
      segmental surgery (SSES) to extirpate the whole disease. RESULTS: Efficacy was
      evaluated strictly by radiographic study. Successful treatment was accomplished
      in 14 (82.4%) patients. Three (17.6%) patients had residual disease; each
      required one revision surgery. None of the patients had recurrence at the time of
      writing. There were no major complications or associated malignancies encountered
      in the patients. CONCLUSION: Endoscopic surgery is an effective treatment for
      recurrent inverted papilloma. Precise determination of the sites of tumor origin
      and attachment during the operation is the key to the successful treatment.
      Recurrent inverted papilloma tends to behave more aggressively and has a higher
      postoperative recurrence rate than the primary lesion. Stage III disease had a
      higher recurrence rate (27.3%) than that of other stages (0%).

PMID- 14710005
TI  - Evaluation of the inferior turbinate in patients with deviated nasal septum by
      using computed tomography.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to measure the dimensions, composition,
      and possible structural and radiological changes of the compensatory hypertrophic
      inferior turbinate in patients with deviated nasal septum. STUDY DESIGN: A
      prospective, nonrandomized clinical trial at a university medical center.
      METHODS: Twenty-three patients with deviated nasal septum and compensatory
      hypertrophy of the inferior turbinate in the contralateral nasal cavity were
      examined by computed tomography. RESULTS: The dimensions of the compensatory
      hypertrophic inferior turbinate in patients with septal deviation were compared
      with normal control subjects. The difference in width of the medial and lateral
      mucosa and the conchal bone between the two groups was statistically significant
      (P <.05). CONCLUSION: The present study uncovers the dimensions and composition
      of the inferior turbinate with compensatory hypertrophy in patients with nasal
      septum deviation. The findings support the decision to excise the inferior
      turbinate bone at the time of septoplasty, because of the significant bony and
      mucosal expansion.

PMID- 14710007
TI  - Smoking in chronic rhinosinusitis: a predictor of poor long-term outcome after
      endoscopic sinus surgery.
AB  - OBJECTIVE: This study was designed to determine whether smoking patients have
      poorer outcomes after endoscopic sinus surgery (ESS) based on a reliable
      validated rhinosinusitis-specific quality-of-life outcomes test. STUDY DESIGN:
      Retrospective chart and computed tomography (CT) review with telephone and letter
      questionnaire. METHODS: Charts of 230 adult patients undergoing ESS for chronic
      rhinosinusitis between January 1995 and December 1998 were reviewed. Each
      participating patient completed a detailed questionnaire, including the Sino
      Nasal Outcome Test-16 (SNOT-16), at an average of 52 months after surgery.
      Preoperative CT scans were reviewed and the findings used to stage the patients'
      conditions. Multivariate analysis was used to assess these data. RESULTS: Eighty
      two patients completed the questionnaire, with 26 who smoked at the time of
      surgery and continued to smoke at the time of answering the questionnaire
      (Smokers). Average SNOT-16 score in Smokers was 27.5, versus 18.2 in those who
      did not smoke at the time of surgery (Non-Smokers). There was a statistically
      significant correlation between elevated SNOT-16 scores and smoking (P <.001) and
      antibiotic use within the past year (P <.001). There was an association between
      high SNOT-16 scores and both prior smoking and passive smoke exposure that did
      not reach statistical significance (P =.055 and P =.267, respectively). CT
      staging scores and prior ESS were not statistically correlated with SNOT-16
      scores. CONCLUSIONS: Smoking is associated with statistically worse outcomes
      after ESS based on average SNOT-16 scores. Although no investigator has proved
      that the effects of smoking on sinonasal health are reversible, we counsel
      smoking patients considering ESS about the desirability of smoking cessation (for
      this and many health reasons), and the possibility of a poorer postsurgery
      outcome should they continue smoking.

PMID- 14710006
TI  - Distribution of 3-nitrotyrosine in the nasal polyps of atopic patients.
AB  - OBJECTIVE: To investigate whether formation of nitrotyrosine in the nasal polyps
      of atopic patients occurs. STUDY DESIGN: A nonrandomized, retrospective,
      controlled qualitative and quantitative study. METHODS: Nasal polyp tissue
      samples were acquired from 12 atopic patients. Control fragments of nasal mucosa
      were taken from 10 patients undergoing corrective surgery of the nasal septum.
      For routine histologic examinations, hematoxylin-eosin staining was used. Low
      magnification microscopy was designed to yield pathologic characteristics and
      high magnification to quantify the number of eosinophils in the subepithelial
      connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical
      method. RESULTS: Hematoxylin-eosin staining revealed presence of numerous
      eosinophils in the epithelium and in the subepithelial connective tissue. All
      polyps were characterized by epithelial damage. Nitrotyrosine was present in the
      eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet
      cells, glands, and vessels were found to be negative. No significant differences
      concerning the localization of nitrotyrosine were recognized among the examined
      nasal polyps. CONCLUSIONS: Nitrotyrosine immunohistochemical staining in nasal
      polyp tissues suggested the existence of progressive epithelium injury caused by
      peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to
      be precisely established. The lack of nitrotyrosine in glands and blood vessels
      indicated that peroxynitrite does not have a significant role in the vascular and
      glandular dysfunction of nasal polyps.

PMID- 14710008
TI  - Microbiology of recurrent acute rhinosinusitis.
AB  - OBJECTIVE: We undertook to evaluate the microbiology of recurrent acute
      rhinosinusitis. METHODS: Repeated aspirations of maxillary sinus secretions by
      endoscopy were performed in eight patients over a period of 98 to 185 days.
      RESULTS: Bacteria were recovered for all 25 aspirates. A total of 31 isolates-14
      Streptococcus pneumoniae, 11 Haemophilus influenzae, 5 Moraxella catarrhalis, and
      1 Staphylococcus aureus-were recovered. The organism persisted in consecutive
      cultures in 13 instances and were eliminated in 8, and new organisms emerged in 6
      instances. An increase in antimicrobial resistance was noted in 5 instances (3 in
      S. pneumoniae and 2 H. influenzae). CONCLUSIONS: This study illustrates the
      microbial dynamics of recurrent acute rhinosinusitis, with the changes in
      microbial findings and increased bacterial resistance that occurs over time.

PMID- 14710009
TI  - Sleep disordered breathing: surgical outcomes in prepubertal children.
AB  - OBJECTIVE: To evaluate the treatment outcomes of sleep disordered breathing (SDB)
      in prepubertal children 3 months following surgical intervention. STUDY DESIGN:
      Retrospective investigation of 400 consecutively seen children with SDB who were
      referred to otolaryngologists for treatment. METHOD: After masking the identities
      and conditions of the children, the following were tabulated: clinical symptoms,
      results of clinical evaluation and polysomnography at entry, the treatment chosen
      by the otolaryngologists, and clinical and polysomnographic results 3 months
      after surgery. RESULTS: Treatment ranged from nasal steroids to various surgical
      procedures. Adenotonsillectomy was performed in only 251 of 400 cases (68%). Four
      cases included adenotonsillectomy in conjunction with pharyngoplasty (closure of
      the tonsillar wound by suturing the anterior and posterior pillar to tighten the
      airway). Persistent SDB was seen in 58 of 400 children (14.5%), and an additional
      8 had persistent snoring. Best results were with adenotonsillectomy. CONCLUSION:
      SDB involves obstruction of the upper airway, which may be partially due to
      craniofacial structure involvement. The goal of surgical treatment should be
      aimed at enlarging the airway, and not be solely focused on treating inflammation
      or infection of the lymphoid tissues. This goal may not be met in some patients,
      thus potentially contributing to residual problems seen after surgery. The
      possibility of further treatment, including collaboration with orthodontists to
      improve the craniofacial risk factors, should be considered in children with
      residual problems.

PMID- 14710010
TI  - Viscoelasticity of rabbit vocal folds after injection augmentation.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold function is related to the viscoelasticity of
      the vocal fold tissue. Augmentation substances used for injection treatment of
      voice insufficiency may alter the viscoelastic properties of vocal folds and
      their vibratory capacity. The objective was to compare the mechanical properties
      (viscoelasticity) of various injectable substances and the viscoelasticity of
      rabbit vocal folds, 6 months after injection with one of these substances. STUDY
      DESIGN: Animal model. METHODS: Cross-linked collagen (Zyplast), double cross
      linked hyaluronan (hylan B gel), dextranomers in hyaluronan (DHIA), and
      polytetrafluoroethylene (Teflon) were injected into rabbit vocal folds. Six
      months after the injection, the animals were killed and the right- and left-side
      vocal folds were removed. Dynamic viscosity of the injected substances and the
      vocal folds was measured with a Bohlin parallel-plate rheometer during small
      amplitude oscillation. RESULTS: All injected vocal folds showed a decreasing
      dynamic viscosity with increasing frequency. Hylan B gel and DiHA showed the
      lowest dynamic viscosity values, and vocal folds injected with these substances
      also showed the lowest dynamic viscosity (similar to noninjected control
      samples). Teflon (and vocal folds injected with Teflon) showed the highest
      dynamic viscosity values, followed by the collagen samples. CONCLUSION:
      Substances with low viscoelasticity alter the mechanical properties of the vocal
      fold to a lesser degree than substances with a high viscoelasticity. The data
      indicated that hylan B gel and DiHA render the most natural viscoelastic
      properties to the vocal folds. These substances seem to be appropriate for
      preserving or restoring the vibratory capacity of the vocal folds when glottal
      insufficiency is treated with augmentative injections.

PMID- 14710011
TI  - Granular cell tumor of the trachea in pregnancy: a case report and review of
      literature.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were to present a case report of a woman
      with recurrent disease during consecutive pregnancies and to discuss the
      diagnosis and management of granular cell tracheal tumors, with particular
      attention to pregnancy and hyperestrogenic states. STUDY DESIGN: Case report and
      literature review. METHODS: A Medline search and comprehensive review of
      literature to assess all cases of granular cell tumors of the trachea were
      compared and collected, with particular attention to individual cases of
      pregnancy or cases related to the hyperestrogenic state. RESULTS: Thirty-two
      cases of granular cell tumors of the trachea were found. Only a few cases related
      to the hyperestrogenic state were obtained. The case report describes a woman
      with recurrent disease in subsequent pregnancies during the later stages of
      pregnancy. CONCLUSION: Few cases of granular cell tumors of the trachea have been
      reported, with even fewer being pregnancy related. The diagnosis and management
      of these tumors include careful attention to patient symptoms and airway
      management.

PMID- 14710012
TI  - Clinical and histological healing of surgical wounds treated with mitomycin C.
AB  - OBJECTIVES/HYPOTHESIS: The proven ability of mitomycin C to inhibit fibroblasts
      in vitro has stimulated its use in research animals and in humans to control
      healing. The objective of the study was to follow the healing process of surgical
      wounds in the dorsum of rats treated topically with mitomycin C. STUDY DESIGN:
      Prospective experimental study. METHODS: Two distinct surgical wounds were made
      to the dorsum of 10 adult rats. One of the wounds received topical mitomycin C
      diluted at 0.5 mg/mL during a 5-minute period, and the other wound was used as a
      control. The healing process was followed clinically and histologically after the
      rats were killed at different post-treatment periods. The degree of fibrosis was
      evaluated histologically by two different pathologists. RESULTS: Surgical wounds
      treated with mitomycin C presented delayed healing when compared with the
      untreated wounds, with remission of scabs 7 days after the control wounds.
      Histological analysis at 1 month after treatment revealed a significant reduction
      in fibrosis of the wounds treated with mitomycin C when compared with the
      untreated wounds. After the third month the degree of fibrosis was comparable in
      both wounds. CONCLUSION: Topical mitomycin C delays the healing of surgical
      wounds in rats up to the fourth week following treatment, but the degree of
      fibrosis is comparable in both treated and untreated wounds after 12 weeks. In
      otolaryngology this characteristic of the drug may be useful in the treatment of
      external ear canal stenosis, choanal atresias, nasal cicatricial stenosis,
      laryngeal stenosis, and keloids.

PMID- 14710013
TI  - Epidermal growth factor receptor in undifferentiated carcinoma of the
      nasopharynx.
AB  - OBJECTIVES: To determine the expression levels of epidermal growth factor
      receptor (EGFR) and its prognostic value in undifferentiated carcinoma (UC) of
      the nasopharynx. STUDY DESIGN: A prospective study of 75 patients diagnosed with
      UC over a 4-year period in a tertiary care hospital. MATERIALS AND METHODS:
      Postnasal space biopsies were obtained and processed, and immunohistochemical
      staining was performed. The over-expression of EGFR was measured, and the
      expression levels were statistically analyzed with the clinical and pathologic
      variables. Disease-free and overall survival analyses were performed. RESULTS:
      There were 62 (82.7%) specimens that showed over-expression of EGFR levels. Over
      expression of EGFR correlated significantly only with primary tumor size (P
      =.007). Age, sex, positive smoking and family history, presence of nodal
      metastasis, distant metastasis, and Epstein-Barr virus serology titers were not
      significantly correlated with over-expression of EGFR. Both 54-month disease-free
      and 56-month overall survivals were not associated with EGFR over-expression.
      CONCLUSION: The frequency of over-expression of EGFR in UC is similar to other
      squamous cell carcinoma (SCC) of the head and neck region. Only primary tumor
      size is independently correlated with over-expression of EGFR. EGFR over
      expression does not affect disease-free and overall survival.

PMID- 14710014
TI  - Recurrent pleomorphic adenoma of the parotid gland: a prospective
      histopathological and immunohistochemical study.
AB  - OBJECTIVES/HYPOTHESIS: Histopathological characteristics and proliferation
      indices of recurrent pleomorphic adenoma were described in a series of 31
      patients who were referred to the authors' clinic for revision surgery. STUDY
      DESIGN: Prospective series of 31 patients. METHODS: Serial sections of surgical
      specimen using the whole-organ sectioning technique were carried out for light
      microscopic examination after total parotidectomy and periparotid fat resection.
      The nodules were examined with special reference to localization, amount, size,
      histological subtypes, capsular alterations, and the amount of nodule spilling.
      Expression of proliferation markers (Ki67/MIB-1) according to the size and
      histological subtypes of the nodules was also investigated. RESULTS: Most
      recurrences were multinodular, and the number of nodules was much higher than
      expected, ranging from 1 to 157. The myxoid subtype was predominant. Eighty
      percent of the patients exhibited widely distributed nodules also lying outside
      the scar. These nodules contained only a thin pseudocapsule and often lacked
      complete encapsulation. The majority of multinodular recurrences of parotid
      pleomorphic adenoma consisted of small nodules (less than 1 mm in diameter).
      Smaller nodules showed similar or higher levels of proliferative activity than
      larger nodules. CONCLUSION: The extended multifocal distribution of tumor
      recurrences after insufficient resection of pleomorphic adenoma (most often after
      enucleation) can explain a high incidence of further recurrences. Therefore, a
      total parotidectomy including removal of surrounding fat tissue seems to be
      appropriate for the initial treatment of recurrent pleomorphic adenoma.

PMID- 14710015
TI  - Orbitozygomatic resection of meningiomas of the orbit.
AB  - OBJECTIVE: To review our experience with the surgical treatment of orbital
      meningiomas. METHODS: A retrospective review of all patients presenting to the
      author for treatment of orbital meningiomas over a 5 year period with a minimum
      of 1 year follow-up were included in this review. Demographic data, surgical
      approaches, and recurrence rates were documented. RESULTS: A total of seven
      patients were treated for this condition. Complete surgical resection was
      achieved with the outlined technique in 71% of the patients, and gross tumor
      removal was achieved in the remaining 29% of patients. This latter group received
      postoperative gamma-knife treatment, and only a single patient has evidence of
      persistent disease that is nonprogressive at 3-year follow-up. CONCLUSIONS:
      Meningioma of the orbit, whether primary (ectopic) or secondary. should be
      treated as at other sites with complete surgical excision if possible. Gamma
      knife or intensity modulated radiotherapy may be useful for residual microscopic
      disease. Surgical clearance is facilitated with the broad field exposure afforded
      by the orbitozygomatic approach outlined in the article, with particular
      attention directed at positive identification of key landmarks particularly in
      retro-orbital and cavernous sinus extension.

PMID- 14710016
TI  - The impact of severe acute respiratory syndrome on otorhinolaryngological
      services at the Prince of Wales Hospital in Hong Kong.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to describe the impact of severe acute
      respiratory syndrome (SARS) on the services of the division of
      otorhinolaryngology-head and neck surgery at an academic tertiary referral
      hospital in Hong Kong. STUDY DESIGN: Descriptive. METHODS: Records of general and
      subspecialty outpatient attendance, ward admissions, ward bed occupancy, and
      elective and emergency surgery were obtained for the period since the SARS
      outbreak and for an equivalent period before the outbreak. The changes in these
      parameters were determined against the background of new SARS cases. RESULTS:
      Since the outbreak of SARS in March 2003, the weekly outpatient clinic attendance
      has declined by 59%, the number of operations performed by 79%, the average ward
      bed occupancy rate by 79% and the daily admission rate by 84%. A dramatic
      increase of 300% in the number of patients defaulting on their outpatient
      appointments was recorded. CONCLUSION: The substantial decrease in
      otorhinolaryngological services at an academic tertiary referral hospital in Hong
      Kong has been multifaceted. The decrease in attendance at the outpatient clinics
      reflects the increased number of patients defaulting on their appointments.
      Nonessential elective surgery was suspended soon after the outbreak, accounting
      for the decrease in the number of surgical procedures performed and partially for
      the decrease in ward bed occupancy and ward admissions. The temporary closure of
      the accident and emergency department contributed to the decrease in ward
      admissions and emergency surgical procedures. The reduced service offered by the
      hospital is having an impact on the quality of care available to patients with
      non-life-threatening otorhinolaryngological conditions.

PMID- 14710017
TI  - Technique of en block laser endoscopic frontolateral laryngectomy for glottic
      cancer.
AB  - During the last 30 years, there has been expansion of the role of endoscopic
      partial laryngectomy procedures since Jako, Strong, and Vaughan explored the
      possibilities of CO2 laser microlaryngeal procedures. Despite the fact that a
      number of investigators have verified the validity of endolaryngeal laser
      resection of mid-sized glottic cancer, there are many who are unfamiliar with the
      technique and others who are uncomfortable with sectioning the tumor to
      facilitate its resection. In the past 3 years, 15 patients underwent successful
      en block resection of mid-sized glottic cancer (T1b 2, T2b 11, T3 2). Because en
      block resection is more consistent with open oncologic approaches, this method
      should widen the acceptance of this approach in selected lesions. The nuances of
      en block endoscopic frontolateral laryngectomy are presented with the hope that
      more surgeons will adopt this philosophy as an aspect of their armamentarium.

PMID- 14710018
TI  - Pharyngeal entry through the vallecula.
AB  - The authors describe a technique of entry into the vallecula with the guide of a
      small Deaver retractor inserted transorally, beyond the tongue base, into the
      vallecula. The tip of the Deaver directs the surgeon to the pharyngotomy site and
      allows pharyngeal entry and access without damaging structures in the region.
      This technique is particularly useful in total laryngectomy with or without
      pharyngectomy and is applicable whenever entry to the pharynx through the
      vallecula is indicated.

PMID- 14710019
TI  - [Neurological manifestations of leprosy].
AB  - Leprosy, also known as Hansen's disease, is a chronic, infectious disease caused
      by Mycobacterium leprae. Bacilli localize preferentially in the skin and
      peripheral nerves and have a propensity to cause nerve damage. The resulting
      disability has caused great suffering for victims in many countries. Despite
      recent advances in the immunopathogenesis, epidemiology and prognostic factors of
      leprosy nerve damage, many aspects of the disease have remained enigmatic. The
      spectrum of clinical and pathological manifestations of the disease ranges from
      lepromatous to tuberculoid, depending on the host's T-cell-mediated immune
      response. Diagnosis is based on three criteria: characteristic skin lesions in
      association with thickened nerves, demonstration of acid fast bacilli in slit
      skin smears, and histopathology of skin biopsies. Nerve biopsy is necessary to
      establish the diagnosis of pure "neural leprosy". In developed countries, the
      diagnosis is suspected when a patient who has stayed in an endemic area suffers
      from a peripheral neuropathy of unknown etiology. To facilitate determination of
      the appropriate antibiotic regimen, patients are classified as either
      paucibacillary or multibacillary. Some patients may have multibacillary leprosy
      in nerves and paucibacillary leprosy in skin, which emphasizes the usefulness of
      nerve biopsy. The course of the disease is often complicated by immune mediated
      "reactions", which can rapidly lead to further nerve damage, namely reversal
      reaction and erythema nodosum leprosy. However, nerves are often functionally
      impaired before developing obvious symptoms such as skin reactions or nevralgia
      (silent neuropathy). Early recognition and prompt treatment with corticosteroids
      of leprous reactions and "silent neuropathies" is very important to prevent
      disability with all its attendant problems. Research progress from clinical
      trials may improve current methods of prevention and treatment of nerve damage in
      leprosy.

PMID- 14710020
TI  - [Functional brain lateralization in children: developmental theories and
      implication for developmental diseases].
AB  - The functional specialization of each hemisphere in adults is now well accepted.
      Neuropsychology of hemispheric functioning in young children is a more debatable
      issue and must take into account additional factors such as development and
      maturation, characterized by complex changes in anatomy and organization. The
      first part of this review describes the theory behind the development of the
      functional organization of the brain. Second, we discuss data regarding brain
      lesions in children with brain damage and with normal development. We comment on
      the concept of plasticity and the critical period. We also discuss the
      neurobiological processes underlying the functional organization of the brain in
      the model of developmental disorders in children. We chose three disorders
      involving the left hemisphere (developmental dysphasia), both hemispheres (benign
      rolandic epilepsy) or the right hemisphere (congenital hydrocephalus) in order to
      examine their relationship to a specific hemispheric functional organization. We
      used classic neuropsychological tests such as the dichotic listening task, the
      dichaptic palpation and the time-sharing paradigm. The patterns observed in each
      pathology are discussed in light of data obtained in children with brain lesions.

PMID- 14710021
TI  - [Routine clinical diagnosis of primary progressive non-fluent aphasia].
AB  - It may be difficult to distinguish between a primary progressive aphasia at a
      very mild stage from the beginning of Alzheimer's disease (AD). However, this may
      be achieved by carrying out simple neuro-psychological tests. Nine non-fluent PPA
      (NFPPA) and 76 AD patients with comparable MMSE as well as 58 control subjects
      were evaluated using simple tests: MMSE, fluency, apraxia, naming, digital span,
      story memory, 5 words memory test. NFPPA patients had significantly impaired
      functions during the semantic category fluency and naming tests as compared to AD
      patients, whereas they showed a better delayed recall of the 5 words and story
      memory tests. As compared to AD, MMSE of NFPPA patients was also better in the
      time orientation and word recall sub-tests, although inferior in words repetition
      and language items. Thus, with comparable MMSE, NFPPA patients have more lexico
      semantic difficulties, but a better delayed verbal memory than AD patients. These
      simple tests easily confirm the language impairment of NFPPA patients as opposed
      to the mnestic difficulties of AD, even at very early stages of these
      pathologies.

PMID- 14710022
TI  - [Cerebellar mutism syndromes with subsequent dysarthria: a study of three
      children and a review of the literature].
AB  - Cerebellar mutism and subsequent dysarthria (MSD) is a possible complication of
      posterior fossa surgery. It is usually seen in children after resection of a
      cerebellar mass lesion. Most patients become mute after a period of (near)normal
      postoperative speech, and are dysarthric once speech resumes. The
      pathophysiological mechanisms underlying MSD are most probably multifactorial,
      combining neuroanatomical, neurophysiological, neuropsychological, and
      psychological factors. The aim of the present article is to better define the MSD
      syndrome. The cerebellum is not only involved in motor control. It is also part
      of a distributed neural circuitry which underlies higher cognitive functions such
      as, for instance, those associated with the programming of kinetic parameters
      before motor initiation of a movement. We hypothesize that it could also be
      involved in the mental initiation which precedes the programming of any
      intentional bucco-phonatory movements to be performed in order to express
      oneself.

PMID- 14710023
TI  - [Parkinson's disease as a model of aging: prospective analysis of gait
      discorders].
AB  - Falls are a dramatic consequence of the age-related gait disorders. There are few
      prospective studies on falls predictive of the biomechanical features of gait.
      According to the literature, there are similarities between the gait observed in
      older people and in parkinsonian subjects. The objective of this study was to
      apply multiparametric gait analysis to demonstrate changes of the neuromotor gait
      pattern connected with falls. This prospective study included two groups of 16
      subjects aged more than 60 years, who had not fallen during the previous year.
      One group included 16 minimally disabled parkinsonian patients off drugs, and the
      other group 16 healthy people. Gait recordings were obtained with a three
      dimensional optoelectronic movement analysis system coupled with 2 force
      platforms in all persons who were followed for 1 year to collect data on all new
      events, particularly falls. Data analysis concerned spatiotemporal stride and
      three-dimensional power peaks developed in each lower limb joint. Cluster
      analysis of the 32 persons was used to determine various infraclinic neuromotor
      gait patterns. A post hoc analysis of variance was then applied to identify
      discriminating parameters. Three groups of subjects were identified with 3
      different neuromotor gait patterns, independently of the presence of Parkinson
      disease. There were no fallers in first group (n=18). The second group (n=8) had
      20 p.cent fallers and the third group (n=4) 100 p.cent fallers. The groups
      differed by 4 spatiotemporal parameters and 3 joint power peaks in the sagittal
      plane. Functional capacity was good in the first group with no falls recorded.
      This group of subjects had characteristics reported in the literature
      corresponding to a category of persons who compensate well for the phenomena of
      aging. Functional capacity was intermediary in the second group (20 p. cent were
      fallers). The kinematic pattern appeared to be less successful, revealing a
      tendency for stiff posture. The third group (100 p. cent fallers) exhibited
      inferior functional capacity. In this group, the kinematic pattern appeared to be
      disrupted. The subjects were unable to adapt satisfactorily to situations other
      than by stereotypical neuromotor reactions. In conclusion this study demonstrated
      a close determinism between physiological neuromotor aging and Parkinson's
      disease. The prospective follow-up demonstrated that falls that occurred were
      related to changes in neuromotor gait patterns. Three phases of gait pattern were
      also identified from minimal to major risk of falls.

PMID- 14710024
TI  - [Functional prognosis of paraplegia due to cord ischemia: a retrospective study
      of 23 patients].
AB  - The functional prognosis of spinal cord infarct is not well known, complicating
      care of patients suffering from ischemic paraplegia. The aim of this study was to
      evaluate the clinical and functional outcome of patients with spinal cord infarct
      treated in rehabilitation centers in order to identify factors influencing
      functional outcome. We studied cases of non-trauma-related paraplegia treated
      between 1992 and 1999. Spinal compression and infectious and inflammatory
      myelopathy were excluded. Age, gender, cardiovascular risk factors, initial and
      final clinical findings according to the American Spinal Injury Association
      (ASIA/IMSOP) criteria, MRI findings, and initial urodynamic findings were
      analyzed. Two groups were identified regarding extension of the spinal cord
      infarct to the cone or not. Assessment of functional outcome was based on the
      Frankel classification, ambulatory ability, wheelchair use, and bladder control.
      Cases of spinal cord infarct were then classified according to extension to the
      cone or not, determined on the basis of initial clinical, MRI, and urodynamic
      findings. Twenty-three patients (19 males and 4 females) were selected for
      analysis. Mean age was 54 years, with no mortality during the follow-up period.
      At discharge, the group of nine patients whose infarct had not extended to the
      medullary cone had a significantly better motor recovery using the ASIA motor
      score (p<0.01). Patients whose infarct did not extend to the cone used
      wheelchairs less often, were more often in Frankel class D (p<0.05), and had
      normal bladder control more often (p<0.05) than patients whose infarct extended
      to the cone. Lack of extension to the medullary cone appeared to be a factor
      predictive of better functional outcome.

PMID- 14710025
TI  - [Guillain-Barre syndrome revealing visceral leishmaniasis in an immunocompetent
      woman].
AB  - Visceral leishmaniasis is an endemic parasitic infection rarely observed in
      association with Guillain-Barre syndrome in immunocompetent patients. A 40-year
      old immunocompetent woman was admitted to our unit with recent onset difficulty
      in walking. The neurological examination and electrophysiological study led to
      the diagnosis of Guillain-Barre syndrome. During hospitalization, she developed
      cytopenia involving all three lines revealing visceral leishmaniasis. A few cases
      of visceral leishmaniasis with neuropathy have been reported, mainly in tropical
      regions. Neuropathological manifestations of visceral leishmaniasis are probably
      underestimated. The question is whether Guillain-Barre syndrome and visceral
      leishmaniasis are causally related.

PMID- 14710026
TI  - [Traumatic dissection of the internal carotid artery: malignant supratentorial
      infarction and decompressive treatment].
AB  - We present a case report of a thirty-six-year-old right-handed female. She
      suffered with a malignant space-occupying supratentorial ischemic stroke caused
      by a traumatic cervical internal carotid artery dissection. She had a car
      accident and, initially, presented with a normal examination. In two days, she
      became comatose (Glasgow Coma Scale score was 5) with complete left hemiplegia,
      right mydriasis and required respiratory assistance despite the medical
      treatment. It was decided to perform a large right frontotemporoparietal bone
      flap with large dural plasty. Eighteen months later, with intensive
      rehabilitation, the results of neuropsychological testing were normal, and the
      Barthel Index score was 90. The indications for decompressive surgery in
      malignant space-occupying supratentorial ischemic stroke remains controversial.
      The age, general condition, neurological examination (consciousness, pupils,
      deficit), extent of parenchymal hypodensity and attenuated corticomedullary
      contrast on the brain CT, degree of midline shift, presence of uncal hernation,
      disparition of the visibility of the mesencephalic cisterns and third ventricle,
      high level of the intracranial pressure, and perhaps the results of the perfusion
      and diffusion-weighted MRI, are the elements to decide (or not decide)
      decompressive surgery.

PMID- 14710027
TI  - [Tramadol-induced epileptic seizures].
AB  - A previously non-epileptic 17-year-old patient presented with 2 generalized
      epileptic seizures, which occurred at 6 months of interval, following the oral
      intake of 200-250 mg of tramadol. Urine analysis showed only the product and its
      metabolites. Epileptic seizures induced by tramadol and high risk factors are
      described and discussed.

PMID- 14710028
TI  - [Primary leiomyosarcoma of the cavernous sinus associated with Epstein-Barr virus
      in a kidney graft].
AB  - Immunodeficient patients have an increased incidence of neoplasms, whether the
      immunodeficiency is due to genetic disorder, the acquired immunodeficiency
      syndrome (AIDS), or immunosuppressive therapy. Leiomyosarcoma (LMS) is a rare
      neoplasm, even if its incidence has increased because of AIDS. Less than fifteen
      cases were described after organ transplantation. An intracranial localization is
      exceptional (five cases in the literature) and was never described after organ
      transplantation, to our knowledge. Our present report focuses on a 45-year-old
      immunocompromised patient, who received immunosuppressive therapy for renal
      transplantation. He suffered from atypical peri-orbital headaches six months
      after transplantation and a mass involving the cavernous sinus was identified.
      Surgical biopsy was performed. Histologic examination revealed a LMS. Epstein
      Barr virus was identified by quantitative polymerase chain reaction in the LMS.
      Immunosuppression was reduced, the patient received adriamycin and protontherapy
      was realized. He died two years after the transplantation because of tumor
      progression and kidney failure.

PMID- 14710029
TI  - [Systemic sarcoidosis revealed by acute ataxic sensory polyradiculoneuropathy].
AB  - We present the case of a 35-year-old man who developed bilateral uveitis and
      acute ataxic sensorial polyradiculoneuropathy with sphincter dysfunction. The
      patient had multiple mediastinal adenopathies. Pathology examination led to the
      diagnosis of sarcoidosis. The patient improved partially spontaneously and
      totally after oral corticosteroid therapy. This case illustrates an unusual
      presentation of acute polyradiculoneuritis which is usually a predominantly motor
      disorder in sarcoidosis. Sensorial and ataxic neuropathy is uncommon. The course
      is more chronic and progressive.

PMID- 14710030
TI  - [Cervical spine manipulation: risks--benefit--assessment].
AB  - Cervical manipulation is a widely used method indicated in non-specific
      mechanical neck pain and cervicogenic headache. Cervical manipulation can cause
      severe neurologic complications which are both rare and generally unpredictable,
      which can be compared with the accidents occurring with other treatments
      (nonsteroidal anti-inflammatory drugs...). To decrease this risk, we propose five
      recommendations developed by consensus: --unwanted effects, however minor (e.g.
      nausea or vertigo), of prior manipulation should be searched for routinely and
      taken as contraindications for future spinal manipulations; --a thorough physical
      examination, including a neurological evaluation should be performed prior to
      manipulation; --all know indications and contraindications should be followed; --
      manipulations should be performed only by physicians experienced in this
      technique; --special caution should be exercised when performing first-line
      cervical manipulation and simple, honest and easily understandable information
      about these risks should be included when informed consent is obtained.

PMID- 14710031
TI  - [Acute motor polyradiculopathy revealing neurosyphilis in an immunocompetent
      patient].

PMID- 14710032
TI  - [Neurological manifestations of temporal arteritis].

PMID- 14710033
TI  - [Contrast ultrasonography: a technological advancement at the service of the
      patient].

PMID- 14710034
TI  - [Detection modes of ultrasound contrast agents].
AB  - Ultrasound contrast agents have been used for many many years in cardiology.
      Their application in other fields is more recent, related to the availability of
      agents that can pass through the pulmonary circulation. Physical properties of
      contrast microbubbles are closely bound to their gas content, shell composition,
      frequency of ultrasound beam, pulse repetition frequency, acoustic power and wave
      phase. Specific ultrasound sequences have to be used to adequately exploit
      microbubble-specific interactions with the ultrasound beam. The aim of this paper
      is to review physical properties of ultrasound contrast agents, present imaging
      sequences developed for optimal use of these contrasts and general applications.

PMID- 14710035
TI  - [Contrast ultrasound imaging in liver disease].
AB  - The recent introduction of high-end ultrasound equipments combined with the
      introduction of contrast agents provides marked improvements in liver imaging for
      the detection and the characterization of focal lesions. Previous imaging methods
      were based on high acoustic power and demonstrated improved detection of focal
      liver lesions. However, good and reliable results were difficult to achieve due
      to limited number of sweeps, as most of the microbubbles were destroyed within
      one pass. Non linear imaging methods at low acoustic power allowed great advances
      in the characterization by limiting signal from background tissue as well as
      agent collapse allowing continuous imaging starting from the time of contrast
      injection until complete disappearance of the agent. Contrast-enhanced imaging of
      the liver follows conventional sonography performed with high standards for
      detection and localization of lesions using multiple sweeps. Then targeted
      acquisition is performed for specific lesion characterization after a second
      contrast injection. Interpretation is based on the presence or not of
      microbubbles within the lesion (hyper-, hypo- or isosignal) and the delay from
      injection (arterial, portal or parenchymal or late phase). A well-recognized
      semiology is reported in this paper. Based on these criteria, sensitivity and
      specificity are close to those reported with other modalities with accuracy 85
      95% for focal liver lesions and 75% for hepatocellular carcinomas. Those results
      markedly improve ultrasound accuracy compared to conventional sonography, and so
      put contrast-enhanced sonography among recommended non-invasive imaging methods
      for focal liver lesions with changes in diagnostic strategy.

PMID- 14710036
TI  - [Contrast-enhanced ultrasonography: renal applications].
AB  - Color Doppler US of the urinary tract is still facing a few limitations
      including, for B-mode imaging, the detection of small lesions, and, for color
      Doppler, the detection of low flow. Ultrasound contrast agents (USCA) improve
      these two limitations and allow the development of new functional applications
      for renal blood flow quantification. This improvement results from an increased
      acoustic response obtained from the microbubbles, as well as from the development
      of pulse sequencing and signal processing that led to the concept of specific
      ultrasound sequences. Most of the clinical indications of contrast-enhanced
      ultrasonography remain to be validated with the improved detection of the non
      linear response. USCA improve the detection of abnormal micro and macrovascular
      disorders of the kidney, particularly for the detection and the characterization
      of renal artery stenosis, as well as for the visualization of renal infarction.
      This technique showed potentials for the study of renal masses, especially
      atypical cystic lesions. Among the remaining indications, the detection of reflux
      and testicular torsion are the most promising.

PMID- 14710037
TI  - [Sonocystography: a new method for the diagnosis and follow-up of vesico-ureteric
      reflux in children].
AB  - Vesicoureteral reflux (VUR) is a common finding in children presenting with acute
      urinary infection, with a frequency ranging from 20 to 50%. If radiological
      retrograde cystography still remains the standard technique, sonocystography now
      appears as a valuable alternative method, due to the properties of recent
      ultrasound contrast agents and the wide use of harmonic imaging. The analysis of
      the literature and the experience acquired by the authors during a clinical trial
      allow summarizing the current data on this new technique. Because of its
      accuracy, it may replace radiological cystography in the detection of VUR in
      girls, the follow-up in both boys and kids, and the management of recurrent
      infection in children presenting with normal radiological cystography.

PMID- 14710038
TI  - [Value of sonographic contrast agents in the evaluation of the cerebral
      arteries].
AB  - Stroke is a frequent and severe disorder. Most strokes are ischemic in nature and
      20% are due to atherosclerosis of the cerebral arteries. Sonographic examination
      plays a key role in the diagnosis and management of patients with cerebrovascular
      disease. However, shortcomings can be encountered in the ultrasound evaluation of
      cervical and intracranial arteries. Contrast agents are known to improve the
      signal / noise ratio and they can therefore compensate for these shortcomings in
      most cases. They have proved to be helpful in unfavorable examinations in daily
      practice. Moreover, their use increases the accuracy and the potential of the
      technique especially in the intra-cranial examination, increasing the role of
      ultrasound techniques.

PMID- 14710039
TI  - [Contrast echocardiography: from experimental validation into practice].
AB  - Contrast echocardiography is at last becoming a reality. The experimental
      validation step has been completed with success and the first clinical results
      bring confirmation. The second generation contrast agents which are becoming
      available on the market, and the spread of enhancement techniques as Real-time
      mode allow perfect visualization of microbubbles within the left ventricular
      cavity, but equally at the level of the myocardial crown, thus targeting two
      direct applications in echocardiography: the first, indisputably, concerns
      improvement in the detection of the endocardium in all situations where it is
      insufficient, and in particular during stress echocardiography; second, more
      ambitious, is with regards to the study of myocardial perfusion with a potential
      role in clinical practice that remains to be determined.

PMID- 14710040
TI  - [Discussion on demographics].

PMID- 14710041
TI  - [Breast cancer screening program in France: recommendations for radiologists].

PMID- 14710042
TI  - [Recommendations for radiologists involved with the breast cancer screening
      program].

PMID- 14710043
TI  - [MRI and in utero ventriculomegaly].
AB  - Ventriculomegaly constitutes the major indication of fetal brain MRI. MRI is
      therefore of utmost importance to look for a cause through the depiction of
      criteria of malformations and through the definition of criteria of destructive
      lesions. Malformations and destructive lesions are the most common causes of
      ventricular dilatation. Some challenging points are worth mentioning in term of
      mechanism with the challenge of hydrocephalus (in term of increased in
      intracranial pressure) and of isolated ventriculomegaly. The image itself is also
      challenging since a similar image may be of different origin. In term of natural
      history of fetal brain injury an irregular, nodular aspect of the ventricular
      wall and/or the germinal matrix is often the only pathologic MRI finding that is
      known to be of clastic origin. In term of prognosis the challenge is represented
      by the isolated mild ventriculomegaly, the literature being quite confusing. The
      purpose of this review paper is to highlight the underlying mechanisms and
      pathophysiology of ventricular dilatation based on results from the literature as
      well as from personal experience.

PMID- 14710044
TI  - [Progress in cardiovascular interventional MRI].
AB  - The purpose of this article is to review recent developments in the field of MR
      guided vascular interventions. Such interventions require real-time visualization
      of catheters and guidewires to define their location with regards to the vascular
      system and surrounding tissues. In the first part of the article, passive and
      active catheter visualization, real-time angiography, and interactivity
      techniques that make guidance of intra-vascular instruments possible are
      described. Subsequently animal coronary and peripheral interventions performed
      under MR guidance are described. MR guided interventions could potentially open
      up new applications for the treatment of cardio-vascular disease in the near
      future.

PMID- 14710045
TI  - [CD-ROM burning of CT scan images: initial experience].
AB  - OBJECTIVES: To evaluate the cost, the functionment and the impact of the
      installation of a CD-ROM burning system of CT scan images. MATERIALS AND METHODS:
      An automated CD-ROM burning system (e-patient*, TSI, Paris, France) allows to
      burn CDs for CT scan examinations containing more than 4 films. During a 3 month
      period, we have delivered for each examination a CD-ROM including images with a
      Dicom viewer and a selection of interesting images printed on one film. The
      system has been evaluated by the technologists, the radiologists and the
      referring physicians by means of a questionnaire. The costs and the technical
      problems have also been studied. RESULTS: The benefits of our system are the
      increase of the diagnostic performances of the referring physicians who use the
      DICOM format and a reduction of the printing costs. All referring physicians
      pointed out major changes in their daily work including difficulties to visualize
      images in relation with a lack of computer infrastructure and the impossibility
      of simultaneous analysis of several examinations. Technologists encountered
      technical problems to bum examinations and radiologists had to do extra work to
      related to image selection. CONCLUSION: The installation of an automated burning
      system requires the creation of a dedicated team to train all the users and adapt
      the presentation of results to the clinical constraints (i.e. performing and
      printing an image selection). This system will not replace the hospital network
      but will be complementary.

PMID- 14710046
TI  - [Advantage of virtual endoscopy in the evaluation of the ossicular chain].
AB  - PURPOSE: Our study consists of a comparison of traditional computed tomography
      (CT) data sets with 2 views of virtual endoscopy in the preoperative evaluation
      of various diseases of the middle ear. MATERIALS AND METHODS: We studied 59
      patients, all sent for conductive hearing loss with normal eardrum who underwent
      a complete CT examination: axial helical acquisition and coronal incremental
      acquisition: virtual endoscopy with selection of two reproducible views: an
      external one of the auditory canal and a lower one of the hypotympanum. Reading
      was performed by 2 independent radiologists. All patients were subsequently
      operated by the same surgeon. Results were compared with surgical reports.
      RESULT: Virtual endoscopy is valuable for the evaluation of ossicular and
      prosthesis dislocations, morphological anomalies of the malleus, incus, and
      stapes superstructure. Nevertheless, standard axial and coronal CT images remain
      necessary as confirmed by the poor results of virtual endoscopy in cases of attic
      obstruction, cholesteatomas and otospongiosis. CONCLUSION: Virtual endoscopy is a
      valuable technique of the evaluation of some ossicular chain pathologies but it
      cannot be used alone.

PMID- 14710047
TI  - [Diagnosis of ectopic mediastinal parathyroid adenomas: value of cardiac MRI].
AB  - Primary hyperparathyroidism is due to an adenoma in 85% of cases. In 10% of
      cases, the parathyroid adenoma may be in an ectopic location. Ten per cent of
      these ectopic adenomas are located in the mediastinum. Imaging modalities
      performed in persistent or recurrent hyperparathyroidism include ultrasound, MIBI
      scintigraphy, venous blood sampling, helical CT and MRI. The authors report 3
      cases of ectopic adenoma located in the mediastinum, where pre-operative
      diagnosis was confirmed using cardiac MRI sequences.

PMID- 14710048
TI  - [Aneurysm of the persistent sciatic artery].
AB  - The authors report a case of persistent sciatic artery presenting with limb
      ischemia and pulsatile mass in the buttock treated only by femoro tibio peroneal
      by pass graft since follow up helical CTA at six months showed spontaneous
      aneurysmal exclusion by thrombosis of the persistent sciatic artery above the
      aneurysm. Review of the literature confirms the rarity of this anomaly, which is
      frequently associated with aneurysmal transformation and its specific inherent
      complications. It is treated by femoro popliteal shunt with endovascular
      embolization.

PMID- 14710049
TI  - [Manubrio-sternal arthritis and behcet's disease: report of 3 cases].
AB  - Manubrio-sternal joint involvement in arthritis is described and may be evidenced
      by erosion, reactive sclerosis and ankylosis. Some reports of such involvement
      appear in the radiological literature in association with psoriatic arthritis and
      spondylarthropathy. Involvement of the manubrio-sternal joint in Behcet's disease
      is very uncommon. To our knowledge, only one case has been described. We report a
      case of manubrio-sternal arthritis in a women with Behcet's disease. Two others
      cases with suspicion of Behcet's disease are described.

PMID- 14710050
TI  - [Carcinoid tumor of the small bowel: value of hydro-MR imaging for diagnosis].
AB  - Hydro-MR imaging is a technique based on the use of a strongly T2-weighted single
      shot fast spin-echo (SSFSE) sequence, similar to that used for MR
      cholangiography. We report herein one case of carcinoid tumor of the small bowel
      diagnosed by hydro-MR imaging. This non invasive MR technique showed suggestive
      features such as radial convergence and segmental dilatation of a small bowel
      loop, similar to those seen on conventional follow-through studies. This case
      illustrates the major role that may be played in the future by hydro-MR imaging
      for the non invasive diagnosis of carcinoid tumor of the small bowel without the
      use of ionizing radiation.

PMID- 14710051
TI  - [Bowel obstruction in pregnancy: value of Single Shot Fast Spin Echo MR sequence
      (SS-FSE)].
AB  - Bowel obstruction is a rare but serious complication of pregnancy for both the
      mother and the developing fetus. The authors report a case of small bowel
      obstruction in an early pregnant patient. Increasing delay between the onset of
      symptoms and the diagnosis remains a significant contributing factor to the high
      morbidity and mortality in the pregnant patient population. So, prompt diagnosis
      and therapy are essential. Single Shot Fast Spin Echo MR sequence confirmed the
      presence of bowel obstruction and identified the zone of transition.

PMID- 14710052
TI  - [Stepping-table MR angiography of the upper limb arteries].
AB  - Stepping-table MR angiography of the upper limb arteries is reported in a patient
      with clinical and sonographic signs of ischemia. Advantages and limitations of
      the technique are discussed.

PMID- 14710053
TI  - [Quid? Ossification of the posterior common vertebral ligament].

PMID- 14710054
TI  - Severe preeclampsia is associated with high inhibin A levels and normal leptin
      levels at 7 to 13 weeks into pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine whether maternal serum
      inhibin A and leptin concentrations changed in the first trimester of pregnancy
      in patients in whom severe preeclampsia subsequently developed. STUDY DESIGN:
      Blood samples were collected prospectively from patients during the first
      trimester of prenatal care. Patients in whom severe preeclampsia with no evidence
      of glucose intolerance or gestational diabetes mellitus subsequently developed
      were identified (study group, 30 patients) and matched with control subjects in a
      1:2 ratio (control group, 60 patients). Inhibin A and leptin concentrations were
      determined in these first-trimester serum samples for both the study and control
      groups. RESULTS: Leptin levels were correlated highly with body mass index in
      both groups but were not correlated with the subsequent onset of preeclampsia.
      Serum inhibin A concentrations were significantly higher in women in whom
      preeclampsia subsequently developed than in women in whom it did not. With a
      specific cutoff value, the estimated odds for severe preeclampsia were almost
      five times higher in women with high inhibin A concentrations than in women with
      normal levels (odds ratio, 4.93; 95% CI, 1.83, 13.28). CONCLUSION: High serum
      inhibin A levels in the first trimester of pregnancy could be used as an early
      risk marker for preeclampsia.

PMID- 14710055
TI  - Impact of oral contraceptive pill use on premenstrual mood: predictors of
      improvement and deterioration.
AB  - OBJECTIVES: The purpose of this study was to estimate risk factors for the
      deterioration and improvement of premenstrual mood disturbance with oral
      contraceptive pill use. STUDY DESIGN: Predictors of the deleterious and
      beneficial effects of oral contraceptive pill use on premenstrual mood were
      analyzed with the use of logistic regression in a nested case-control study
      within a community-based cohort of 976 premenopausal women in Massachusetts.
      RESULTS: Of 658 women who were using oral contraceptive pills, 16.3% of the women
      reported oral contraceptive pill-related premenstrual mood deterioration, and
      12.3% of the women reported premenstrual mood improvement. In adjusted models,
      previous depression was the only significant predictor of mood deterioration
      (odds ratio, 2.0; 95% CI, 1.1-3.8); early-onset premenstrual mood disturbance and
      dysmenorrhea were significant predictors of oral contraceptive pill-related mood
      improvement (odds ratio, 3.1 [95% CI, 1.9-5.2] and odds ratio, 2.3 [95% CI, 1.4
      3.9], respectively). CONCLUSION: Oral contraceptive pills do not influence
      premenstrual mood in most women. Premenstrual mood is most likely to deteriorate
      in women with a history of depression and to improve in women with early-onset
      premenstrual mood disturbance or dysmenorrhea.

PMID- 14710056
TI  - Thriving in the midst of chaos: Presidential address.

PMID- 14710057
TI  - Utility of preemptive local analgesia in vaginal hysterectomy.
AB  - OBJECTIVE: Our purpose was to determine whether preemptive administration of long
      acting local anesthetics before vaginal hysterectomy will improve postoperative
      pain. STUDY DESIGN: A blinded, randomized, trial of paracervical injection of
      0.5% bupivacaine with epinephrine or normal saline solution placebo with
      epinephrine was conducted. Verbal analog pain scores were collected at 1, 2, 3,
      4, 6, and 24 hours after surgery. Morphine use in the postanesthesia care unit
      and by patient-controlled morphine analgesia was recorded. RESULTS: Twenty
      patients were enrolled. Nine were randomized to bupivacaine. There was no
      difference between groups regarding age, length of surgery, blood loss, or length
      of stay. Pain scores were lower in the bupivacaine group by analysis of variance
      (P=.03). Total morphine and patient-controlled analgesia morphine was
      significantly less in patients receiving bupivacaine (P=.01 and.04). CONCLUSION:
      Paracervical block with a 0.5% bupivacaine with 1:200,000 epinephrine before
      vaginal hysterectomy is associated with lower pain scores and a reduction in
      morphine requirements after surgery.

PMID- 14710059
TI  - Fecal and urinary incontinence after vaginal delivery with anal sphincter
      disruption in an obstetrics unit in the United States.
AB  - OBJECTIVE: The purpose of this study was to estimate the incidence of urinary and
      bowel incontinence in relation to anal sphincter laceration in primiparous women
      and to identify factors that are associated with anal sphincter laceration in a
      unit that uses primarily midline episiotomy. STUDY DESIGN: From January 1, 1997,
      to March 30, 2000, 2941 questionnaires concerning pelvic floor function 6 months
      after delivery were mailed to primiparous women who were delivered vaginally at
      the University of Michigan Medical Center. Charts were reviewed for 2858
      deliveries to assess the use of episiotomy and the degree of perineal trauma,
      along with demographic and pertinent delivery variables. There were 943 women who
      completed the urinary function questionnaire and 831 women who completed the
      bowel function questionnaire. Univariate analysis was performed on all
      covariates. Multiple logistic regression was used for the analysis of the
      presence of third- or fourth-degree lacerations as the outcome. RESULTS: Nineteen
      percent of the women who completed the survey had sustained third- or fourth
      degree lacerations during childbirth. The women in the sphincter laceration group
      were more likely (23.0%) to have bowel incontinence than the women in the control
      group (13.4%) (P<.05). The incidence of worse bowel control was nearly 10 times
      higher in women with fourth-degree lacerations (30.8%) compared with women with
      third-degree lacerations (3.6%, P<.001). Macrosomia (odds ratio, 2.19; 95% CI,
      1.61, 2.99), forceps-assisted delivery (odds ratio, 4.75; 95% CI, 3.43, 6.57),
      and vacuum-assisted delivery (odds ratio, 3.51; 95% CI, 2.64, 4.66) were
      associated with higher risks of third- and fourth-degree lacerations. Midline
      episiotomy (odds ratio, 2.24; 95% CI, 1.81, 2.77), but not mediolateral (odds
      ratio, 0.66; 95% CI, 0.375, 1.19), episiotomy was associated with anal sphincter
      lacerations. More than one half of the women had new onset of urinary
      incontinence after delivery and reported several lifestyle modifications to
      prevent leakage. CONCLUSION: Women with third- and fourth-degree lacerations were
      more likely to have bowel incontinence than women without anal sphincter
      lacerations. Fourth-degree lacerations appear to affect anal continence greater
      than third-degree lacerations.

PMID- 14710061
TI  - Patient-selected goals: a new perspective on surgical outcome.
AB  - OBJECTIVE: This study was undertaken to study the relationship between
      achievement of patient goals, overall satisfaction, and objective outcome
      measures. STUDY DESIGN: After Institutional Review Board approval, we
      prospectively evaluated 78 women undergoing pelvic reconstructive surgery at
      Loyola University Medical Center. After informed consent for surgery, patients
      were asked to state their goals for surgery. In a follow-up telephone
      conversation, these goals were reviewed and negotiated to modify expectations.
      The same physician investigator contacted women 3 months after surgery to assess
      goal achievement, overall satisfaction, and their surgical experience. Date were
      analyzed with Spearman correlation and Mann-Whitney tests. RESULTS: Of 78 women,
      75% indicated that they met most of their goals, and 72% were more than 80%
      satisfied. Patient satisfaction was moderately correlated to goal achievement
      (rho=0.57, P<.001). Objective cure, defined as no urodynamic stress incontinence
      and stage 0 or I prolapse, was not related to satisfaction (P=.14).
      Dissatisfaction was highly associated with feeling "unprepared for surgery"
      (P<.001). CONCLUSION: Objective and subjective outcomes are necessary to predict
      patient satisfaction.

PMID- 14710063
TI  - A randomized, controlled trial to compare ketorolac tromethamine versus placebo
      after cesarean section to reduce pain and narcotic usage.
AB  - OBJECTIVE: The purpose of this study was to determine whether postcesarean
      section administration of ketorolac tromethamine reduces pain and narcotic usage.
      STUDY DESIGN: A double-blinded randomized, placebo-controlled trial of ketorolac
      tromethamine was performed. Patients were randomly assigned to receive either
      ketorolac tromethamine or placebo. Patient-controlled analgesia (PCA) was used
      for pain control. Visual analog scales (VAS) were administered postoperatively to
      assess pain levels. Morphine equivalents and attempts were recorded. RESULTS:
      There were 22 patients in each arm of the study. There was no significant
      difference between patient demographics, blood loss, and type of anesthesia. Pain
      scores were significantly different at 2, 3, 4, 6, 12, and 24 hours by analysis
      of variance (ANOVA) (P=.033). There was a significant decrease in pain medication
      usage (P=.008) in the study group. CONCLUSION: Ketorolac tromethamine is
      efficacious in reducing postoperative pain and narcotics usage after cesarean
      section.

PMID- 14710067
TI  - McIndoe procedure for vaginal agenesis: long-term outcome and effect on quality
      of life.
AB  - OBJECTIVE: The purpose of this study was to evaluate quality of life, sexual
      function, and long-term outcome in women after undergoing the McIndoe procedure
      for vaginal agenesis. STUDY DESIGN: This was a retrospective descriptive study of
      patients who were treated with the McIndoe procedure for vaginal agenesis.
      Participants answered a structured questionnaire to describe self-reported
      outcomes in quality of life, sexual function and satisfaction, and body image
      after the McIndoe procedure. Patient characteristics along with short- and long
      term findings were abstracted from the medical record. RESULTS: Eighty-six
      patients responded to the questionnaire. Average age (+/-SD) at surgery was 21+/
      6 years (range, 12-49 years). The mean number of years (+/-SD) since surgery was
      23+/-12 (range, 2-50 years). Seventy-nine percent of the respondents stated that
      the McIndoe procedure improved their quality of life. Ninety-one percent of the
      respondents were sexually active, with 75% able to achieve orgasm. Reported self
      image was improved in 55% of the women. CONCLUSION: The McIndoe procedure
      improves quality of life and sexual satisfaction and provides a functional vagina
      with minimal complications.

PMID- 14710065
TI  - The safety of incidental appendectomy at the time of abdominal hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to assess the complication rates of
      incidental appendectomies in women who undergo benign gynecologic procedures.
      STUDY DESIGN: This was a retrospective case-controlled study of patients who did
      (n=100 women) or did not (n=100 women) undergo incidental appendectomies at the
      time of an abdominal hysterectomy between June 1995 and January 2001. Information
      was abstracted from hospital and clinic records and a gynecologic oncology
      database. Data were obtained about age, body mass index, hypertension, diabetes
      mellitus, the number of days with nothing by mouth, the length of hospital stay,
      and postoperative complications (cellulitis, fever, ileus, pneumonia,
      thromboembolic disease). Data were analyzed with the use of two-sample t tests,
      Wilcoxon Rank sum tests, chi(2) tests, and multiple logistic regressions.
      RESULTS: There was no difference in preoperative diagnosis or operative procedure
      for either group. The number of patients in the group that did have incidental
      appendectomy versus the group that did not have incidental appendectomy with
      additional procedures at the time of abdominal hysterectomy was bilateral
      salpingo-oophorectomy (66 vs 61 women), unilateral oophorectomy (19 vs 19 women),
      lysis of adhesions (9 vs 8 women), and others (12 vs 8 women). Compared with the
      group that did not have incidental appendectomy, the group that did have
      incidental appendectomy was younger (mean age+/-SD: 44+/-9.6 years vs 48+/-13.6
      years, P=.02) and had a lower mean body mass index (26.1+/-6.0 kg/m(2) vs 29.8+/
      8.9 kg/m(2), P=.0009). No significant differences were found between the two
      groups (the group that did have incidental appendectomy vs the group that did not
      have incidental appendectomy, respectively) with respect to the following
      postoperative complications: fever (40 vs 27 women), cellulitis (1 vs 2 women),
      wound collection (4 vs 6 women), wound dehiscence (1 vs 5 women), wound abscess
      (7 vs 6 women), ileus (3 vs 2 women), and urinary tract infection (4 vs 10
      women). The mean length of hospital stay was significantly longer in the group
      that did have incidental appendectomy than in the group that did not have
      incidental appendectomy (3.6+/-1.52 days vs 3.1+/-1.1 days, P=.006). However, the
      difference was no longer significant when patients who were fed electively on the
      postoperative day 2 were excluded from the analysis (3.16+/-1.13 days vs 3.04+/
      1.13 days, P=.507). Thirty-one percent of the histologic specimens were abnormal,
      with fibrous obliteration being most common, and there was one case of acute
      appendicitis. CONCLUSION: An incidental appendectomy at the time of benign
      gynecologic procedures does not increase postoperative complication rates or
      length of hospital stay. The inclusion of incidental appendectomies in all
      abdominal hysterectomies could potentially decrease the morbidity and mortality
      rates because of appendicitis in elderly women.

PMID- 14710069
TI  - Anatomy of ilioinguinal and iliohypogastric nerves in relation to trocar
      placement and low transverse incisions.
AB  - OBJECTIVE: The purpose of this study was to map the course of the ilioinguinal
      and iliohypogastric nerves. STUDY DESIGN: The courses of iliohypogastric and
      ilioinguinal nerves from 11 fresh frozen cadavers were mapped from their lateral
      emergence on the anterior abdominal wall to their midline termination in
      reference to fixed bony landmarks. Bivariate fit ellipses were generated for each
      nerve and compared with sites of standard abdominal surgical incisions. RESULTS:
      Thirteen iliohypogastric and 16 ilioinguinal nerves were identified and mapped.
      On average, the proximal end of the ilioinguinal nerve entered the abdominal wall
      3.1 cm medial and 3.7 cm inferior to the anterior superior iliac spine, then
      followed a linear course to terminate 2.7 cm lateral to the midline and 1.7 cm
      superior to pubic symphysis. The iliohypogastric nerve entered the abdominal wall
      on average 2.1 cm medial and 0.9 cm inferior to the anterior superior iliac
      spine, which followed a linear course to terminate 3.7 cm lateral to the midline
      and 5.2 cm superior to pubic symphysis. CONCLUSION: Abdominal wall surgical sites
      below the level of the anterior superior iliac spine have the potential for
      ilioinguinal or iliohypogastric injury.

PMID- 14710071
TI  - Abdominal hysterectomy for the enlarged myomatous uterus compared with vaginal
      hysterectomy with morcellation.
AB  - OBJECTIVE: The purpose of this study was to compare intraoperative and
      postoperative complications of abdominal hysterectomy for the enlarged, myomatous
      uterus with vaginal hysterectomy with morcellation. STUDY DESIGN: Medical records
      of 139 patients who underwent vaginal hysterectomy with morcellation and 244
      patients who underwent total abdominal hysterectomy for an enlarged, myomatous
      uterus between August 1990 and July 2001 were reviewed. Uterine weights of >982 g
      were excluded because this was the largest uterus removed vaginally, which left
      208 evaluable cases of total abdominal hysterectomy. The perioperative and
      postoperative course of the two groups was compared. The Student t test was used
      for continuous variables, and the Fisher exact test was used for binary or
      categoric data. RESULTS: There were no significant differences between the two
      groups in surgical or anesthetic risk factors (P>.05). Operative time was similar
      between the groups (P>.05). Length of hospital stay was increased significantly
      with total abdominal hysterectomy (mean, 3.9 days vs 2.6 days; P<.001).
      Perioperative complications were increased with the abdominal route (10% vs 25%,
      P<.001). CONCLUSION: In this large series, uterine morcellation at the time of
      vaginal hysterectomy is safe and facilitates the removal of moderately enlarged
      and well-supported uteri and is associated with decreased hospital stay and
      perioperative morbidity rate compared with the abdominal route.

PMID- 14710073
TI  - Morbidity and mortality rates of elective gynecologic surgery in the elderly
      woman.
AB  - OBJECTIVE: The purpose of this study was to report perioperative morbidity and
      mortality rates in elderly women who undergo gynecologic surgery. STUDY DESIGN:
      The charts of 54 consecutive women ages 70 to 85 years who underwent major
      gynecologic surgery between June 1998 and November 2002 were reviewed
      retrospectively. RESULTS: The mean age was 76.7 years. Fifty procedures (92.6%)
      were performed for pelvic organ prolapse and/or urinary incontinence. Forty-nine
      of the procedures were performed vaginally, and 27 of the procedures (50%) were
      performed with the use of general anesthesia. Postoperative cardiac complications
      occurred in five patients (10%), including three myocardial infarctions, two of
      which were fatal. Other complications included benign cardiac arrhythmias in two
      patients, slow return of gastrointestinal function in five patients (9.3%), and
      transient mental status changes in four patients (7.4%). The mean length of stay
      was 4 days. CONCLUSION: Postoperative complications occurred infrequently among
      elderly women who underwent gynecologic surgery. Although age alone is not a
      contraindication to elective surgery, there may be increased risks for geriatric
      women.

PMID- 14710075
TI  - Cadaveric fascia lata sling for stress urinary incontinence: a prospective
      quality-of-life analysis.
AB  - OBJECTIVE: The purpose of this study was to describe the effects of full-length
      cadaveric fascia lata (CFL) sling on quality-of-life outcomes. STUDY DESIGN:
      Patients were 102 women (aged 29 to 87 years) who underwent the sling procedure
      for stress incontinence associated with intrinsic sphincter deficiency. They were
      followed up at 12, 24, 36, and 48 months with the Incontinence Impact
      Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI-6), and a patient
      satisfaction questionnaire. RESULTS: Mean IIQ score declined from 55.1 before
      surgery to 11.0 at 12 months (P<.001). Mean UDI score declined from 67.1 to 28.0
      at 12 months (P<.01). At 12 months, 79.7% of patients reported that leakage was
      better or much better, and 90.2% reported that they were somewhat or completely
      satisfied with their progress. Results were maintained throughout the 48-month
      follow-up period. CONCLUSION: The CFL sling procedure has an enduring beneficial
      effect on lower urinary tract symptoms and quality of life.

PMID- 14710077
TI  - Collagen content of nonsupport tissue in pelvic organ prolapse and stress urinary
      incontinence.
AB  - OBJECTIVE: Reduction in the collagen content of the pelvic floor tissue of the
      patients with pelvic organ prolapse and/or stress urinary incontinence has been
      documented previously. However, this is less clear for nonsupport tissue. We
      aimed to compare the collagen content of the uterine cervix, a nonsupport tissue,
      of women who had pelvic organ prolapse with and without stress urinary
      incontinence against those without these problems. STUDY DESIGN: Cervical
      collagen content was compared between 14 women who had pelvic organ prolapse with
      and without stress urinary incontinence and 17 controls without these conditions.
      Specimens were obtained after surgery for benign gynecologic conditions. RESULTS:
      Groups were similar with respect to age, parity, body mass index, and tobacco
      use. Women who had pelvic organ prolapse with and without stress urinary
      incontinence possessed significantly less collagen compared with the controls
      (8.10%+/-3.43% vs 12.35%+/-4.72%, P=.0104). Furthermore age, parity, body mass
      index, or tobacco use had no significant relationship to collagen content.
      CONCLUSION: Cervical collagen content is significantly decreased in women who
      have pelvic organ prolapse with and without stress urinary incontinence
      regardless of age, parity, body mass index, or tobacco use.

PMID- 14710079
TI  - Tension-free vaginal tape procedure is an ideal treatment for obese patients.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of obesity on
      the success of the tension-free vaginal tape (TVT) procedure for stress urinary
      incontinence. Specifically, do patients with a body mass index (BMI) of 35
      kg/m(2) or greater have a lower cure rate of stress urinary incontinence? STUDY
      DESIGN: This retrospective cohort study identified 35 patient pairs who had
      undergone TVT in Winnipeg, Manitoba, Canada, for stress urinary incontinence from
      November 1999 to July 2001. Obese patients (defined as BMI greater than or equal
      to 35 kg/m(2)) were paired with nonobese patients (defined as BMI less than or
      equal to 30 kg/m(2)). The subjects were matched for age (within 5 years) and
      prior continence surgeries. Patients with a maximum urethral closure pressure of
      less than or equal to 20 cm H(2)O were excluded. Follow-up was either by
      objective cough stress test or subjective cure assessed by telephone interview.
      Cure was defined as no postoperative stress incontinence. Statistical analysis
      was performed by conditional logistic regression for matched controls. RESULTS:
      The follow-up range was 6 to 24 months. There were seven failures in all, four in
      obese and three in nonobese patients, giving cure rates of 88.6% and 91.4%,
      respectively. This difference was not statistically significant (P>.05). There
      were five bladder perforations (identified at the time of the procedure), all
      occurring in nonobese patients (P< .05). CONCLUSION: These data do not
      demonstrate a difference in cure of TVT in obese versus nonobese patients. Given
      the finding of fewer complications, this procedure may be an ideal surgical
      treatment modality for stress urinary incontinence in obese women.

PMID- 14710081
TI  - Long-term results of abdominal sacrocolpopexy.
AB  - OBJECTIVE: Our purpose was to determine the long-term results after abdominal
      sacrocolpopexy. STUDY DESIGN: Computer-coded procedure logs identified women who
      had an abdominal sacrocolpopexy performed from 1985 to 1992. Subjects answered a
      validated, condition-specific symptom questionnaire, a sexual function
      questionnaire, and a demographic survey. Failures were defined by reoperation or
      symptoms. The data were analyzed with use of the Student t test and the Fisher
      exact test. RESULTS: At the time of surgery the subjects (n=38) had a mean age of
      59.2 years (range 40-77 years), parity 4.03 (1-9), BMI 26.5 (18.6-40.2), and
      stage of prolapse 2.56 (0-4). The mean follow-up interval was 13.7 years (10-17
      years). The total number of failures was 10 (26.3%), 4 (10.5%) because of
      reoperation and 6 (16%) because of symptoms. Symptom distress scores were low and
      similar between failures and successes. Twelve subjects were available for
      examination and most defects were noted in the anterior wall. CONCLUSION: This
      long-term outcome analysis of abdominal sacrocolpopexy found the procedure to be
      durable with a 74% success rate at a mean follow-up of 13.7 years.

PMID- 14710083
TI  - Vaginal paravaginal repair with an AlloDerm graft.
AB  - OBJECTIVE: This study was undertaken to describe outcomes of a technique of
      vaginal paravaginal repair that used AlloDerm graft (LifeCell, Branchburg, NJ) in
      women with recurrent stage II or with primary or recurrent stage III/IV anterior
      vaginal wall prolapse. STUDY DESIGN: This was an observational study. Thirty
      three women underwent a vaginal paravaginal repair using AlloDerm graft. Anterior
      vaginal wall prolapse was staged using the pelvic organ prolapse quantification
      system preoperatively and every 6 months after surgery. Recurrence of prolapse,
      changes in functional status (urinary symptoms, prolapse symptoms, and sexual
      activity), and complications were recorded. Objective failure was defined as
      recurrent anterior vaginal wall prolapse, stage II or greater, and subjective
      failure as symptomatic recurrent anterior vaginal wall prolapse. Life-table
      analysis evaluated objective and subjective failure. Risk factors for recurrent
      anterior vaginal wall prolapse were evaluated. RESULTS: The mean age was 65.2
      years and 93% of the women were white. Preoperatively, 6 women had recurrent
      stage II, 24 women had stage III, and 3 women had stage IV anterior vaginal wall
      prolapse. The median length of follow-up was 18 months. Postoperatively, 12 women
      had asymptomatic stage II anterior vaginal wall prolapse (not beyond the hymen)
      develop, and 1 woman had symptomatic stage II prolapse develop. Thus, there were
      13 (41%) objective failures and 1 (3%) subjective failure. Life-table analysis
      demonstrated the cumulative probability of an objective failure was 0.24 at 1
      year and 0.50 at 2, 3, and 4 years. The cumulative probability of a subjective
      failure was 0.00 at 1 and 2 years and 0.11 at 3 and 4 years. No risk factors for
      objective failure were identified. Voiding complaints resolved in 11 of 14 (79%)
      women (P=.004), incontinence symptoms resolved in 17 of 19 (89%) women (P<.001),
      and urgency symptoms resolved in 20 of 23 (87%) women (P<.001) (all two-tailed
      Fisher exact test). Twenty-one women (64%) were sexually active, and none
      complained of postoperative dyspareunia. Complications included 1 case of febrile
      morbidity, 1 cystotomy, and 1 anterior wall breakdown secondary to hematoma
      formation caused by heparin therapy. No other erosions or rejections were seen.
      CONCLUSION: Vaginal paravaginal repair with AlloDerm graft in women with
      recurrent stage II or stage III/IV anterior vaginal wall prolapse is safe and has
      good subjective but only fair objective success within the first 2 years.

PMID- 14710085
TI  - Effects of oxidized regenerated cellulose on the expression of extracellular
      matrix and transforming growth factor-beta1 in human peritoneal fibroblasts and
      mesothelial cells.
AB  - OBJECTIVE: The purpose of this study was to evaluate the potential biologic
      effects of oxidized regenerated cellulose, which has been shown in multiple human
      in vivo studies to reduce postoperative adhesion development, on the messenger
      RNA levels of transforming growth factor-beta1, type I collagen, type III
      collagen, and fibronectin. STUDY DESIGN: The oxidized regenerated cellulose was
      dissolved in saline solution and added to confluent, monolayer cultures of human
      normal fibroblasts and mesothelial cells. Control cells were maintained in media
      alone at the same pH. After 24 hours of treatment, total RNA was extracted from
      all cells. Real-time reverse transcription-polymerase chain reaction was
      performed to determine the relative change in messenger RNA levels of type I,
      type HI collagen, fibronectin, transforming growth factor-beta1, and beta-actin
      (housekeeping gene) in response to the oxidized regenerated cellulose treatment
      (n=4 cultures). Student t tests were performed for each cell type, which compared
      oxidized regenerated cellulose-treated cells to control cells. Calculated power
      for the statistically significant findings ranged from 65% to 100%. RESULTS:
      Transforming growth factor-beta1 messenger RNA was elevated by the oxidized
      regenerated cellulose treatment in the mesothelial cells by 13% (control cells,
      0.562+/-0.022; oxidized regenerated cellulose-treated cells, 0.636+/-0.014;
      P=.03). In normal fibroblasts, transforming growth factor-beta1 messenger RNA was
      slightly, but not significantly, decreased in oxidized regenerated cellulose
      exposed normal fibroblasts compared with controls (control cells, 0.622+/-0.062;
      oxidized regenerated cellulose-treated cells, 0.609+/-0.006; P=.85). Type I
      collagen was found to be increased by exposure to oxidized regenerated cellulose
      in both mesothelial cells and normal peritoneal fibroblasts. Type I collagen was
      increased by 23% in mesothelial cells (control cells [0.587+/-0.018] vs oxidized
      regenerated cellulose-treated cells [0.722+/-0.010], P=.002), and 27% in normal
      fibroblasts (control cells, 0.522+/-0.018, oxidized regenerated cellulose-treated
      cells, 0.665+/-0.009; P=.001). However, messenger RNA levels of type III collagen
      and fibronectin (other representative molecules of the extracellular matrix) were
      not altered significantly by oxidized regenerated cellulose application in vitro.
      CONCLUSION: Oxidized regenerated cellulose influences the expression of factors
      that are accepted commonly to be associated with adhesiogenesis. Oxidized
      regenerated cellulose increased the expression of transforming growth factor
      beta1 in mesothelial cells and type I collagen in mesothelial cells and normal
      peritoneal fibroblasts. Minimization of these oxidized regenerated cellulose
      induced molecular changes, if they occur in vivo, may improve the ability of
      oxidized regenerated cellulose to reduce postoperative adhesion development.

PMID- 14710087
TI  - Prevalence of anal incontinence among mothers of multiples and analysis of risk
      factors.
AB  - OBJECTIVE: The object of this study was to determine the prevalence of anal
      incontinence among women with previous multiple pregnancy and childbirth and
      assess risk factors. STUDY DESIGN: A 77-item questionnaire was administered to
      769 mothers of multiples. Statistical analyses included chi(2), Student t test,
      and logistic regression. RESULTS: Seven hundred thirty-three (95.3%) women
      completed the survey, 94% of them white, with a median age of 37 years. Fecal
      incontinence affected 10% (6.3% arose during pregnancy, 40.6% after delivery,
      53.1% unrelated to childbirth). Although delivery by cesarean section only was
      associated with lower prevalence in univariate analysis (5.8% vs 11%, P=.02), age
      was the only significant covariate in multivariate regression (P=.0001). Flatal
      incontinence affected 25.2% (21.2% during pregnancy, 30.3% after delivery, 48.5%
      unrelated), increasing with age (P=.0001). Soiling affected 10%, increasing with
      age (P=.0001). CONCLUSION: Mothers of multiples reported substantial rates of
      fecal (10%) and flatal (25.2%) incontinence. Advancing age was the major risk
      factor. Delivery by cesarean section only was not significantly protective,
      although elective (before labor) cesarean deliveries were not separately
      assessed.

PMID- 14710089
TI  - Adoption of the pelvic organ prolapse quantification system in peer-reviewed
      literature.
AB  - OBJECTIVE: The purpose of this study was to examine the method of describing
      pelvic organ prolapse in the peer-reviewed literature since the introduction of
      the Pelvic Organ Prolapse Quantification System (POPQ). STUDY DESIGN:
      Representative US and international gynecology and urology journals were selected
      for review. All prolapse or urinary incontinence articles published in these
      journals from January to December of 1999 (period 1) and July 2001 to June 2002
      (period 2) were hand searched by two independent reviewers. Systems for grading
      the severity of pelvic organ prolapse were separated into the following
      categories: POPQ, Baden-Walker system, Beecham system, grade without reference,
      or nonstandardized system. Chi-square and Fisher exact tests were used for
      statistical analysis. RESULTS: A prolapse staging system was not referenced, or a
      nonstandardized staging system was used in 54.8% of studies. Overall, the POPQ
      system was the most common system used (22.6%), followed by the Baden-Walker
      system (19.8%). There was a statistically significant increase in the use of POPQ
      from period 1 (13.3%) to period 2 (28%) (P=.03). Articles published in gynecology
      journals were more likely to use the POPQ system than those published in urology
      journals (29% vs. 14%, P=.009). CONCLUSION: POPQ was the most common system used;
      however, the staging system was not cited or a nonstandardized staging system was
      used in more than half of studies.

PMID- 14710091
TI  - Effect of periurethral denervation on function of the female urethra.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of periurethral
      denervation on contractile function of the female rat urethra. STUDY DESIGN:
      Periurethral nerve transection or sham operation was performed in 16 young female
      rats. After 2 weeks, contractile function of the external urethra sphincter (EUS)
      and longitudinal smooth muscle was determined. Inhibitors of nitric oxide (NO)
      signaling were used to evaluate the role of nitric oxide in nerve-mediated
      relaxation. Statistical comparisons were conducted by Student t test. RESULTS:
      Periurethral nerve transection resulted in gross evidence of urinary retention
      and bladder distention. In normal and sham-operated rats, nerve-mediated
      relaxation of urethral smooth muscle was inhibited by L-nitroarginine and
      oxadiazolo quinoxalin-1-one (ODQ), and this relaxation response was impaired
      significantly after periurethral nerve injury. Relaxation responses to the NO
      donor sodium nitroprusside remained intact. Contractile function of the EUS was
      not altered by periurethral nerve injury. CONCLUSION: Neurons surrounding the
      urethra contain NO and innervate smooth muscle of the inner urethra. Periurethral
      denervation results in impaired urethral smooth muscle relaxation with no
      appreciable effect on contractility of the external striated sphincter.

PMID- 14710092
TI  - Menopause-related symptoms: what are the background factors? A prospective
      population-based cohort study of Swedish women (The Women's Health in Lund Area
      study).
AB  - OBJECTIVE: The purpose of this study was to analyze the influence of
      sociodemographic characteristics and environmental factors on self-reported
      menopause-related symptoms among middle-aged Swedish women. STUDY DESIGN: Women
      who were born in the years 1935 to 1945 and who were living in the Lund area of
      southern Sweden were investigated. Each woman completed a generic questionnaire
      and underwent a personal interview that pertained to sociodemographic
      characteristics, lifestyle, and current health-related problems. With these
      background factors, the frequency and intensity of hot flushes and vaginal
      dryness were determined; risk factor analysis was evaluated with the use of the
      multiple regression models. RESULTS: There were 6917 participants, with a
      response rate of 64%. A lower risk for hot flushes was related to older age, high
      education, and vigorous physical exercise. The major risk factors for vasomotor
      complaints were current weight gain, part-time employment, oophorectomy,
      unhealthy lifestyle, and concomitant health problems. Light smoking, late age of
      menopause, higher education, and excessive weight reduced the risk of vaginal
      dryness. However, older age, marriage, and chronic diseases negatively affected
      vaginal complaints. The background factors had less impact on symptoms in women
      who used hormone replacement therapy. CONCLUSION: Sociodemographic
      characteristics, lifestyle, and concomitant health problems appear to be
      important modifiable determinants for menopause-related symptoms.

PMID- 14710093
TI  - Glycosaminoglycan profile in bladder and urethra of castrated rats treated with
      estrogen, progestogen, and raloxifene.
AB  - OBJECTIVE: This study was undertaken to evaluate the action of conjugated equine
      estrogens alone, medroxyprogesterone, the combination of these estrogens with
      progestogens, and of raloxifene on the glycosaminoglycan profile in the bladder
      and urethra of adult oophorectomized rats in comparison with noncastrated rats.
      STUDY DESIGN: Sixty adult rats, of which 50 were submitted to bilateral
      oophorectomy, were studied. After 4 days, the latter were assigned to five groups
      of 10 animals each. For 30 consecutive days the following treatments were given:
      group 1, conjugated equine estrogens; group 2, conjugated equine estrogens
      combined with medroxyprogesterone acetate; group 3, medroxyprogesterone; group 4,
      raloxifene; and group 5, placebo. Thereafter the bladders and urethras of the
      animals were removed, processed to yield a dry powder of which the sulfated
      glycosaminoglycan content was determined by densitometry after agarose gel
      electrophoresis and that of hyaluronic acid by a fluorimetric assay. RESULTS:
      Glycosaminoglycans found in the bladder and urethra were dermatan sulfate,
      heparan sulfate, and hyaluronic acid. In the bladder, hypoestrogenism or
      replacement with estrogens led to a lower sulfated glycosaminoglycan content.
      Replacement with estrogens and/or medroxyprogesterone reverted this effect.
      Hypoestrogenism decreased the dermatan sulfate/heparan sulfate ratio and reduced
      hyaluronic acid content. Estrogen therapy reverted this alteration and
      medroxyprogesterone addition annulled the estrogenic effect. In the urethra,
      castration did not alter hyaluronic acid content and sulfated glycosaminoglycan
      content, but raloxifene decreased the latter. CONCLUSION: Castrated rats had a
      decrease in sulfated glycosaminoglycans and hyaluronic acid content in the
      bladder. Hormonal replacement altered the quantity and quality of
      glycosaminoglycans. In the urethra, raloxifene reduced sulfated
      glycosaminoglycans.

PMID- 14710094
TI  - High intraepithelial expression of estrogen and progesterone receptors in the
      transformation zone of the uterine cervix.
AB  - OBJECTIVE: Because sex hormones may be involved in tumor initiation and
      progression, we analyzed the presence of hormone receptors in the transformation
      zone of the uterine cervix where the majority of human papillomavirus infections
      and associated (pre)neoplastic lesions develop. STUDY DESIGN: By using 23 total
      hysterectomy samples from young women who underwent surgery for noncervical
      benign uterine disease, we analyzed, by immunohistologic techniques, the in situ
      expression of estrogen (E(2)-R) and progesterone (P(4)-R) receptors in the
      transformation zone and ectocervix of the same women. RESULTS: The expression of
      estrogen receptors and progesterone receptors is significantly higher in the
      transformation zone compared with the ectocervix. Immunohistochemical
      localization indicated that hormone receptor-positive cells are mainly observed
      in (para)basal and intermediate cell layers in both the transformation zone and
      ectocervical epithelium. When transformation zone samples were segregated into
      epithelial tissues with a predominantly mature (7/23 samples) or immature (16/23
      samples) squamous metaplasia, only biopsy specimens with immature squamous
      metaplasia showed a significantly higher density of hormone receptor-positive
      cells compared with ectocervical epithelium (P<.01). CONCLUSION: Our results
      suggest that the cervical transformation zone may be at increased risk of the
      development of cancer because of a high sensitivity to sex hormone regulation.

PMID- 14710096
TI  - Modified technique for suprapubic catheter insertion that avoids urinary leakage.
AB  - When a large bore suprapubic catheter, such as a Foley catheter, is required for
      postoperative drainage of the bladder, nearly 10% of patients experience urinary
      leakage. We describe a novel technique involving the tubularization of the
      bladder during large bore suprapubic catheter placement to prevent urinary
      leakage while the catheter is in place and after its removal.

PMID- 14710095
TI  - Membrane-associated serine/threonine protein phosphatase in endometrial cancer.
AB  - OBJECTIVE: Reversible serine/threonine protein phosphorylation catalyzed by
      kinases and phosphatases plays a crucial role in cellular growth and
      differentiation. We attempted to determine the subcellular location of
      serine/threonine phosphatase (protein phosphatase type 2A [PP2A]) in endometrial
      cancer. STUDY DESIGN: Endometrial cancers surgically removed were examined. PP2A
      activity was assessed by measuring the dephosphorylation of phosphopeptide highly
      selective for the PP2A in cytosol and membranes fractionated on a continuous
      sucrose density gradient. Its protein level was detected by immunoblotting with a
      specific antibody. RESULTS: There were three peaks of PP2A enzyme activity and
      immunoreactivity corresponding by marker enzyme analysis to the cytoplasm, plasma
      membrane, and endoplasmic reticulum fractions. An enzyme kinetic analysis showed
      the different activity in cytosol and plasma membrane; K(m) values of 98+/-12
      micromol/L for cytosol and 32+/-6.2 micromol/L for plasma membrane (P<.01),
      respectively. The membrane phosphatase was sensitive to inhibition by okadaic
      acid and sodium fluoride, characteristics suggestive of PP2A activity.
      CONCLUSION: PP2A activity in the plasma membrane of endometrial cancers might be
      distinct from that present in the cytosol. The plasma membrane PP2A may be
      responsible for a rapid and initial decrease in intracellular level of
      phosphoserine and phosphothreonine, interfering with serine/threonine protein
      phosphorylation-mediated growth of endometrial cancer.

PMID- 14710097
TI  - Gastroschisis: the effect of labor and ruptured membranes on neonatal outcome.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      labor and ruptured membranes on the neonatal outcome of infants with
      gastroschisis. STUDY DESIGN: We reviewed the outcomes of 60 neonates who were
      prenatally diagnosed with gastroschisis and who were delivered at the University
      of North Carolina Hospitals between June 1989 and April 1999. RESULTS: The mean
      gestational age at delivery was 36 weeks. Four infants (7%) died in the neonatal
      period, and 19 infants (32%) had a major morbidity. No significant differences
      appeared in any of the neonatal outcomes when they were stratified by the
      presence or absence of labor and presence or absence of ruptured membranes. After
      being controlled for confounding variables, the risk of neonatal death or major
      neonatal morbidity because of exposure to either labor or ruptured membranes was
      no different than the risks caused by no labor or intact membranes, respectively.
      CONCLUSION: Labor and ruptured membranes do not appear to be associated with
      increased neonatal morbidity or mortality rates in neonates with gastroschisis.

PMID- 14710098
TI  - Effectiveness of cervical cerclage for a sonographically shortened cervix: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of
      cerclage for a shortened cervix on transvaginal ultrasound scanning in terms of
      the rates of preterm delivery and adverse neonatal and maternal outcomes. STUDY
      DESIGN: Pre-MEDLINE and MEDLINE, EMBASE, and the Cochrane Library were searched
      for human studies that compared cerclage placement to no cerclage on the basis of
      transvaginal ultrasound findings of a short cervix (< or =2.5 cm). Two authors
      independently determined eligibility and abstracted data. Meta-analyses were
      conducted when possible. RESULTS: Thirty-five studies were reviewed; 6 studies
      were eligible and were included in the analysis. There was no statistically
      significant effect of cerclage on the rates of preterm delivery (<37, <34, <32,
      and <28 weeks of gestation), preterm labor, neonatal mortality or morbidity,
      gestational age at delivery, or time to delivery. Birth weight was significantly
      higher with than without cerclage (P=.004). CONCLUSION: The available evidence
      does not support cerclage for a sonographically detected short cervix. A
      randomized controlled trial is needed to determine whether this intervention will
      reduce adverse neonatal outcomes.

PMID- 14710099
TI  - Does cerclage location influence perinatal outcome?
AB  - OBJECTIVE: The study was undertaken to measure cerclage location within the
      cervix and to determine whether placement closer to the internal os is related to
      perinatal outcome. STUDY DESIGN: We analyzed data collected during a randomized
      trial of cervical cerclage versus no cerclage that was conducted at Lehigh Valley
      Hospital between May 1998 and June 2001 in women with ultrasound findings of
      short cervix less than 25 mm or funneling between 16 and 24 weeks' gestation.
      Women who were randomly assigned to the cerclage arm had cervical measurements
      performed before cerclage, including dilation of the internal os, depth of
      membrane prolapse into the endocervical canal, cervical length below any funnel
      (distal length), and total cervical length (including any funnel). Measurements
      obtained after cerclage placement included the distance from external os to
      cerclage (A), and a repeat of the same four measurements. The distance from the
      external os to the cerclage (A) was divided by the total cervical length (B) and
      a cerclage to cervical length ratio (A/B) was calculated. The relationship
      between these measurements and gestational age at birth was assessed by linear
      regression analysis. RESULTS: Of 150 patients enrolled, 74 received a McDonald
      cerclage suture. Mean distal cervical length was 1.9+/-0.9 cm before and 2.9+/
      1.0 cm after cerclage (P=.001). The mean distance between the cerclage and
      external os (A) was 1.8+/-0.6 cm; the total cervical length after cerclage (B)
      was 3.6+/-0.9 cm. The mean cerclage to cervical length ratio (A/B) was 0.5+/-0.1.
      Linear regression analysis did not demonstrate a correlation between either the
      cerclage to external os measurement (A) or the cervical length ratio (A/B) and
      gestational age at birth (R(2)=0.0006 and 0.008, P=.8 and.6, respectively).
      CONCLUSION: The length of the cervix below the level of cerclage is not related
      to duration of pregnancy in women treated with cerclage because of ultrasound
      evidence of cervical effacement.

PMID- 14710100
TI  - Vaginal administration of the nitric oxide donor isosorbide mononitrate for
      cervical ripening at term: a randomized controlled study.
AB  - OBJECTIVE: Our aim was to examine the effect of the nitric oxide donor isosorbide
      mononitrate on the uterine cervix at term and to evaluate possible adverse
      effects of this treatment. STUDY DESIGN: Term pregnant women were randomly
      selected to receive either 40 mg vaginally administered isosorbide mononitrate or
      placebo 4 hours before elective cesarean section. Cervical status, maternal blood
      pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler
      indices, and various side effects were examined. RESULTS: Isosorbide mononitrate
      induced a significant increase in cervical distensibility. It also caused a
      significant change in maternal blood pressure and maternal pulse rate. In
      addition, the frequency of maternal headache and palpitations was significantly
      higher in the isosorbide mononitrate group versus the placebo group. However, the
      intensity of these symptoms was moderate. CONCLUSION: Vaginal administration of
      40 mg of isosorbide mononitrate induces cervical ripening at term. Although the
      majority of women experienced side effects, no serious clinical maternal or fetal
      adverse effects, resulting in specific medication or emergency cesarean section,
      were diagnosed.

PMID- 14710101
TI  - Increased fetal adiposity: a very sensitive marker of abnormal in utero
      development.
AB  - OBJECTIVE: Because offspring of women with gestational diabetes mellitus have an
      increased risk of obesity and diabetes mellitus as young adults, our purpose was
      to characterize body composition at birth in infants of women with gestational
      diabetes mellitus and normal glucose tolerance. STUDY DESIGN: One hundred ninety
      five infants of women with gestational diabetes mellitus and 220 infants of women
      with normal glucose tolerance had anthropometric measurements and total body
      electrical conductivity body composition evaluations at birth. Parental
      demographic, anthropometric, medical and family history data, and diagnostic
      glucose values were used to develop a stepwise regression model that related to
      fetal growth and body composition. RESULTS: There was no significant difference
      in birth weight (gestational diabetes mellitus [3398+/-550 g] vs normal glucose
      tolerance [3337+/-549 g], P=.26) or fat-free mass (gestational diabetes mellitus
      [2962+/-405 g] vs normal glucose tolerance [2975+/-408 g], P=.74) between groups.
      However, infants of women with gestational diabetes mellitus had significantly
      greater skinfold measures (P=.0001) and fat mass (gestational diabetes mellitus
      [436+/-206 g] vs normal glucose tolerance [362+/-198 g], P=.0002) compared with
      infants of women with normal glucose tolerance. In the gestational diabetes
      mellitus group, although gestational age had the strongest correlation with birth
      weight and fat-free mass, fasting glucose level had the strongest correlation
      with neonatal adiposity. CONCLUSION: Infants of women with gestational diabetes
      mellitus, even when they are average weight for gestational age, have increased
      body fat compared with infants of women with normal glucose tolerance. Maternal
      fasting glucose level was the strongest predictor of fat mass in infants of women
      with gestational diabetes mellitus. This increase in body fat may be a
      significant risk factor for obesity in early childhood and possibly in later
      life.

PMID- 14710102
TI  - Maternal morbidity and perinatal outcomes among pregnant women with respiratory
      hospitalizations during influenza season.
AB  - OBJECTIVES: A population-based assessment of maternal and perinatal morbidity
      related to respiratory illness during influenza season among pregnant women has
      not been published. The objectives of this investigation were to describe and
      quantify the impact of respiratory hospitalization during pregnancy on serious
      maternal and perinatal morbidity. STUDY DESIGN: A matched cohort study using an
      administrative database of pregnant women enrolled in the Tennessee Medicaid
      population to determine pregnancy outcomes associated with respiratory
      hospitalizations during influenza season. Pregnant women aged 15 to 44 years with
      a respiratory hospitalization during influenza seasons 1985-1993 were matched by
      gestational age and presence of comorbidity with pregnant control subjects
      without a respiratory hospitalization. RESULTS: During the eight influenza
      seasons studied, 293 women with singleton pregnancies had respiratory disease
      hospitalizations (5.1:1000). Women with asthma had high rates of such
      hospitalization (59.7:1000). Compared with matched controls, women with
      respiratory hospitalizations had similar modes of delivery, delivery length of
      stay, and episodes of preterm labor. The prevalence of prematurity and low birth
      weight among infants born to such women was likewise similar between the two
      groups. CONCLUSION: In this population of pregnant women, those with asthma
      accounted for half of all respiratory-related hospitalizations during influenza
      seasons, with 6% of pregnant women with asthma requiring respiratory
      hospitalization during influenza season, (odds ratio 10.63, 95% CI, 8.18-13.83,
      compared with women without a medical comorbidity). We detected no significant
      increase in adverse perinatal outcomes associated with respiratory
      hospitalizations during influenza season.

PMID- 14710103
TI  - Maternal myo-inositol, glucose, and zinc status is associated with the risk of
      offspring with spina bifida.
AB  - OBJECTIVE: The purpose of this study was to investigate the maternal and
      children's myo-inositol, glucose, and zinc status in association with spina
      bifida risk. STUDY DESIGN: Sixty-three mothers and 70 children with spina bifida
      and 102 control mothers and 85 control children were investigated. The maternal
      and child serum myo-inositol, serum glucose, and red blood cell zinc
      concentrations were measured when the child was between 1 and 3 years old. These
      data were compared between cases and control subjects. The association with spina
      bifida was expressed by the ratio of geometric means and by odds ratios and 95%
      CI for a cutoff value at the extreme 10th percentile of the control group.
      RESULTS: The geometric mean of the maternal myo-inositol concentration tended to
      be 5% (95% CI, -1% to 11%) lower in cases. Interestingly, the odds ratio for the
      extreme low maternal myo-inositol concentration was 2.6 (95% CI, 1.1-6.0). The
      glucose and zinc concentrations were significantly higher at 7% (95% CI, 4%-10%)
      and significantly lower at 5% (95% CI, 0%-9%), in case mothers compared with
      control mothers. The odds ratios (95% CI) for maternal high glucose and low zinc
      concentrations were 4.6 (2.0-10.5) and 2.9 (1.2-7.0), respectively. The geometric
      mean of the myo-inositol concentration tended to be 7% (95% CI, 0%-14%) lower in
      children with spina bifida; the glucose and zinc concentrations were comparable.
      CONCLUSION: Maternal myo-inositol, glucose, and zinc status are associated with
      the risk of spina bifida in offspring. Furthermore, the myo-inositol status of
      the child seems to contribute to this risk as well.

PMID- 14710104
TI  - Effects of maternal antioxidant supplementation on maternal and fetal antioxidant
      levels: a randomized, double-blind study.
AB  - OBJECTIVE: We sought to determine whether vitamins C and E could be delivered to
      the fetal-placental unit through maternal oral supplementation. STUDY DESIGN: In
      a randomized, double-blind study, 20 women received a daily prenatal vitamin with
      or without 400 IU of vitamin E and 500 mg of vitamin C, starting at 35 weeks'
      gestation. At randomization, a nutritional questionnaire, plasma vitamin C and E
      and red blood cell (RBC) vitamin E levels were determined. At delivery,
      concentrations of maternal and fetal plasma vitamin C and E, maternal and fetal
      RBC vitamin E, amniotic fluid vitamin C, and chorioamnion vitamin E and tensile
      strength were determined. RESULTS: Maternal plasma vitamin E levels increased in
      the supplemented women but not in the control subjects. No changes in maternal
      vitamin C levels were noted. Maternal plasma vitamin C concentrations at delivery
      correlated closely with amniotic fluid vitamin C levels. Similarly, maternal
      plasma vitamin E levels at delivery correlated with the chorioamnion
      concentration of vitamin E. CONCLUSIONS: Maternal plasma vitamin E levels are
      increased by oral supplementation. Maternal plasma vitamin C and E concentrations
      correlate with the concentration of vitamin C in the amniotic fluid and vitamin E
      in the chorioamnion, respectively.

PMID- 14710105
TI  - Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy
      outcomes.
AB  - OBJECTIVE: The purpose of this study was to correlate low maternal pregravid
      weight, delivery weight, and poor gestational weight gain with perinatal
      outcomes. STUDY DESIGN: Maternal and perinatal data from January 1997 to June
      2001 were obtained from a perinatal database at MetroHealth Medical Center. Low
      maternal weight (LMW) was defined as pregravid or delivery weight <100 pounds or
      body mass index (BMI) < or =19.8 kg/m(2). Low maternal weight gain was defined as
      <0.27 kg per week. Perinatal complication rates in these subjects were compared
      with those with weights of 100 to 200 pounds, normal BMI (>19.8, <26 kg/m(2)),
      and normal gestational weight gain (0.27-0.52 kg/wk). Chi-square and t tests were
      used where appropriate. P<.05 was significant. RESULTS: A percentage (2.6%) of
      15,196 subjects began pregnancy weighing < or =100 pounds; 0.15% weighed <100
      pounds at delivery and 13.2% had a pregravid BMI < or =19.8 kg/m(2). Pregravid
      LMW was highly correlated with ethnicity (Asians, 8.6%; Hispanics, 4.3%;
      Caucasians, 2.5%; African Americans, 1.9%; P<.001). Subjects with pregravid LMW
      were at increased risk for intrauterine growth restriction (IUGR) (relative risk
      [RR], 2.3, 95% CI, 1.3-4.05), and perineal tears (3rd-degree lacerations; RR,
      1.8, 95% CI, 1.1-2.9), and low birth weight ([LBW] <2500 g; RR, 1.8, 95% CI, 1.1
      2.9). They had a lower risk of cesarean section (RR, 0.72, 95% CI, 0.56-0.92) and
      preterm delivery (PTD) (RR, 1.1, 95% CI, 0.97-1.06). Pregravid BMI <19.8 kg/m(2)
      was associated with preterm labor (PTL) (RR, 1.22, 95% CI, 1.02-1.46), IUGR (RR,
      1.67, 95% CI, 1.2-2.39), and LBW (<2500 g; RR, 1.13, 95% CI, 1.0-1.27) and was
      protective against cesarean delivery (RR, 0.8, 95% CI, 0.71-0.91). Delivery LMW
      was associated with LBW (<2500 g; RR, 2.81, 95% CI, 1.62-4.84), active-phase
      arrest (RR, 5.07, 95% CI, 1.85-13.9), PTL and PTD (RR, 2.5, 95% CI, 1.02-6.33,
      and RR, 2.45, 95% CI, 1.4-4.4, respectively), a lower gestational age at delivery
      (36.8 vs 38.3 wks, P<.05), and mediolateral episiotomy (RR, 9.6, 95% CI, 1.9
      48.0). A percentage (0.8%) of subjects had BMI <19.8 kg/m(2) at delivery. Low
      delivery BMI was associated with birth weight <2500 g (RR, 1.74, 95% CI, 1.3
      2.32), PTL (RR, 2.16, 95% CI, 1.45-3.19), and PTD (RR, 1.57, 95% CI, 1.18-2.11).
      Failure to thrive in pregnancy (weight gain <0.27 kg/wk) was associated with LBW
      (<1500 g; RR, 1.23, 95% CI, 1.03-1.45), <2500 g; RR, 1.22, 95% CI, 1.13-1.33),
      and PTL and PTD (RR, 1.2, 95% CI, 1.05-1.37, and RR, 1.11, 95% CI, 1.02-1.2,
      respectively). CONCLUSION: Low weight and BMI at conception or delivery, as well
      as poor weight gain during pregnancy, are associated with LBW, prematurity, and
      maternal delivery complications.

PMID- 14710106
TI  - Stillbirth and neonatal outcomes in South Australia, 1991-2000.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of maternal
      factors associated with impaired placental function on stillbirth and neonatal
      death rates in South Australia. STUDY DESIGN: From 1991 to 2000, the South
      Australian Pregnancy Outcome Unit's population database was searched to identify
      stillbirths and neonatal deaths in women with maternal medical conditions during
      pregnancy and in twin and singleton pregnancies. RESULTS: Women with hypertension
      and carbohydrate intolerance and who smoked during pregnancy had an increased
      risk of stillbirth. Women with twin pregnancies had a significantly higher
      stillbirth rate than for singletons at each week of gestational age. An increase
      in stillbirth rate at later gestations was seen with singletons, with a similar
      trend in twins but rising from 36 weeks' gestation. CONCLUSION: There is a
      clinical correlation between maternal factors associated with impaired placental
      function and increased risk of stillbirth, suggesting that intrauterine fetal
      death represents the mortality end point in a spectrum of intrauterine hypoxia.

PMID- 14710107
TI  - Effect of the antenatal administration of celecoxib during the second and third
      trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in
      rabbits.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of celecoxib on
      prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. STUDY
      DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A),
      from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood
      and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation
      products. RESULTS: Preterm delivery occurred in 4 of 11 controls, 0 of 9 in
      celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F(2alpha) was
      reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma
      thromboxane B(2) was suppressed in celecoxib-B at 20 days and delivery. Cervical
      prostaglandin E(2) was increased; uterine and cervical plasma thromboxane B(2)
      declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide
      oxidation products at delivery and cervical nitric oxide oxidation products in
      celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were
      decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B.
      CONCLUSION: Further studies are required to evaluate the therapeutic benefits of
      cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.

PMID- 14710108
TI  - Response of fetal prostanoids, nitric oxide, and ductus arteriosus to the short-
      and long-term antenatal administration of celecoxib, a selective cyclo-oxygenase
      2 inhibitor, in the pregnant rabbit.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that the maternal
      administration of therapeutic doses of celecoxib would not affect ductus
      arteriosus patency or alter renal and hepatic prostanoids in the fetal rabbit.
      STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib
      A), from 13-28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Fetal
      serum and lung tissue were analyzed for nitric oxide oxidation products. Fetal
      plasma, liver, and kidney were analyzed for prostaglandin levels. RESULTS: The
      ductus arteriosus was patent in both treatment groups. Celecoxib induced
      elevations of plasma prostaglandin E(2) production. In celecoxib-B liver and
      kidney, the 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) levels
      were increased, and the prostaglandin E(2) and thromboxane B(2) levels were
      decreased substantially. CONCLUSION: This preliminary evaluation demonstrates
      that the maternal administration of celecoxib does not influence fetal ductus
      arteriosus patency adversely in rabbits.

PMID- 14710109
TI  - Pharmacokinetics of betamethasone after maternal or fetal intramuscular
      administration.
AB  - OBJECTIVE: The purpose of this study was to determine the pharmacokinetics of
      betamethasone in maternal and fetal circulations after maternal or fetal
      intramuscular administration. STUDY DESIGN: Ewes that bore single fetuses
      underwent surgery at approximately 96 days of pregnancy for the implantation of
      fetal and maternal vascular catheters. At approximately 103 days, five ewes were
      injected intramuscularly with betamethasone (0.5 mg/kg body weight) or five
      fetuses received ultrasound-guided intramuscular injections of betamethasone (0.5
      mg/kg estimated fetal weight). Maternal and fetal blood samples were collected
      serially for the measurement of plasma betamethasone concentrations. RESULTS:
      Fetal injection caused higher peak fetal betamethasone concentrations (341.2+/
      23.7 nmol/L) than maternal injection (37.6+/-3.7 nmol/L; P<.001) and greater
      cumulative betamethasone exposure. The half-life of betamethasone in the fetal
      circulation was shorter after fetal injection (1.1+/-0.3 hours) than after
      maternal injection (8.5+/-2.0 hours; P=.006). CONCLUSION: The duration of fetal
      and maternal exposure to betamethasone can be minimized by direct fetal
      intramuscular administration that, in sheep, affords lung maturation without
      adverse effects on fetal growth.

PMID- 14710110
TI  - Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2
      inhibition by N-acetylcysteine in the human term decidua and fetal membranes.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of N
      acetylcysteine on the activity and secretion of the matrix metalloproteinases in
      the decidua, amnion, and chorion and the secretion of the tissue inhibitor of
      matrix metalloproteinase-1. STUDY DESIGN: Samples from eight nonlaboring women
      were taken at elective cesarean section and incubated in an in vitro organ
      culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase
      2 and matrix metalloproteinase-9 activity was measured with the use of gel
      zymography. Western blot analysis was used to measure matrix metalloproteinase
      and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed
      with the paired Student t test. RESULTS: N-acetylcysteine had a direct inhibitory
      effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity,
      regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L
      N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix
      metalloproteinase-9 activity in all three tissues. A differential response was
      demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue
      that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20
      mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at
      all in chorion. Matrix metalloproteinase-9 secretion was not affected in a
      statistically significant manner in any tissue. In the chorion, matrix
      metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor
      of matrix metalloproteinase-1 secretion significantly decreased in the decidua at
      20 mmol/L. CONCLUSION: N-acetylcysteine, at higher concentrations, has an
      inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9
      activity, regardless of the tissue origin and the differential effect on
      secretion depending on the tissue and N-acetylcysteine concentration.

PMID- 14710111
TI  - Renal and placental secretion of erythropoietin during anemia or hypoxia in the
      ovine fetus.
AB  - OBJECTIVE: The source of the erythropoietin (EPO) that circulates in the fetus is
      unknown although it is known that EPO does not cross the placenta and that fetal
      kidneys, liver, and placenta express the EPO gene. This study tested to what
      extent in vivo EPO secretion by the fetal kidneys and placenta can be
      demonstrated under normoxic and hypoxic conditions. STUDY DESIGN: Renal arterial
      and venous EPO concentrations were determined in eight late-gestation chronically
      catheterized fetal sheep made progressively anemic by exchange transfusion with
      saline solution over 5 to 8 days. In a separate additional series of experiments,
      umbilical arterial and venous EPO concentrations were determined in nine normoxic
      fetuses and in nine fetuses subjected to 12 hours of hypoxia induced by lowering
      maternal-inspired oxygen content. Organ secretion rates were calculated as the
      product of plasma flow rate and the arteriovenous concentration differences.
      RESULTS: Renal vein plasma EPO concentration was higher than the arterial
      concentration in 36 of 40 paired samples (P<.0001) by 16.3%+/-2.7% (mean+/-SE).
      This difference was concentration independent over a range of 12 to 4100 mU/mL.
      Renal EPO secretion rates were variable and averaged 155+/-105 mU/min when
      hematocrit was 31.3%+/-1.6% (n=5) and 1124+/-300 mU/min post-exchange transfusion
      when hematocrit was 15.6%+/-0.8% (n=12). In contrast, umbilical venous and
      arterial EPO concentrations (range 9-35 mU/mL), although highly correlated
      (r=0.94), were not different during normoxia (Po(2)=21.6+/-0.5 mm Hg, n=9). Under
      hypoxic conditions (Po(2)=15.6+/-0.4 mm Hg, n=9), umbilical vein EPO
      concentration (range 151-1245 mU/mL) was higher than arterial concentration
      (range 140-951 mU/mL) in eight of nine paired samples by 13.6%+/-3.3% (P<.01).
      Under these conditions, estimated umbilical EPO secretion rate was 27,900+/
      11,500 mU/min. CONCLUSION: Under nonanemic, normoxic basal conditions, the
      kidneys secreted EPO into the fetal circulation, whereas secretion by the
      placenta was not demonstrated. In the phlebotomy-induced fetal anemia
      experiments, the kidney demonstrated marked, progressive increases in the rate of
      EPO production. Similarly, in the fetal hypoxemia experiments, the placenta
      demonstrated progressive increases--albeit an order of magnitude greater than the
      kidneys--in EPO production rate. As an extension of these findings, we speculate
      that the hypoproliferative neonatal anemia that invariably occurs in the early
      weeks after birth is in part the result of loss of EPO production by the
      placenta.

PMID- 14710113
TI  - Chorioamnionitis induced by subchorionic endotoxin infusion in sheep.
AB  - OBJECTIVE: This study was undertaken to determine whether subchorionic endotoxin
      infusion causes chorioamnionitis and preterm lung maturation, as occurs after
      intra-amniotic endotoxin. STUDY DESIGN: From day 118 of pregnancy, sheep received
      infusions of endotoxin (subchorionic 7.5 mg/d, n=11; intra-amniotic 2.5 mg/d,
      n=9) until delivery of lambs at 120 or 124 days. Other sheep received a single
      intra-amniotic injection of endotoxin (10 mg, n=7) at 118 days before delivery at
      124 days. Controls (n=9) received equivalent saline solution treatments. RESULTS:
      Chorioamnionitis accompanied all endotoxin treatments. Lung inflammation occurred
      after intra-amniotic endotoxin infusion or injection but not after subchorionic
      endotoxin. Umbilical arterial pH was lower and Pco(2) was higher than control
      after subchorionic endotoxin. Lung compliance and surfactant were increased after
      intra-amniotic endotoxin infusion or injection but not after subchorionic
      endotoxin. CONCLUSION: Chorioamnionitis may result from inflammatory stimuli at
      various intrauterine sites, with different sites causing different fetal effects
      and not all cases of chorioamnionitis being accompanied by enhanced lung
      maturation.

PMID- 14710114
TI  - Human maternal and fetal plasma glyceryl trinitrate concentrations.
AB  - OBJECTIVE: This study was undertaken to determine the maternal and fetal steady
      state concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites
      during transdermal administration, at the time of fetal blood sampling for
      obstetric indications. STUDY DESIGN: Transdermal GTN (0.4 mg/h) was applied
      approximately 2 hours before investigative fetal blood sampling to maintain
      uterine quiescence. Serial maternal venous (MV) and a single fetal venous (FV)
      plasma samples were collected and assayed for GTN and its metabolites, 1,2- and
      1,3-glyceryl dinitrate. RESULTS: The steady-state MV plasma concentration was
      4.3+/-0.84 nmol/L (mean+/-SEM, n=7), and the dinitrate metabolites were
      detectable in the MV but not quantifiable. GTN was detectable in the FV (n=7) but
      was not quantifiable as the levels were less than the lower limit of sensitivity
      of the assay (<1 nmol/L). CONCLUSION: During transdermal GTN administration, the
      steady-state FV/MV concentration ratio is less than 0.23 at the time of fetal
      blood sampling.

PMID- 14710115
TI  - Cord C-peptide and insulin-like growth factor-I, birth weight, and placenta
      weight among North African and Belgian neonates.
AB  - OBJECTIVE: Despite their low socioeconomic status, infants of North African
      immigrants have been reported to have high birth weights in Belgium. The aim of
      the study was to further explore potential mechanisms explaining this high birth
      weight. STUDY DESIGN: Venous umbilical cord blood samples and perinatal
      characteristics of live-born infants from mothers of North African and Belgian
      nationality were collected in 1997 through 1998 at the University Hospital La
      Citadelle, Liege, Belgium. RESULTS: The median connecting peptide (C-peptide)
      concentration was significantly higher among North African than Belgian neonates
      (0.125 vs 0.110 pmol/mL, P=.04). However, the median insulin-like growth factor-I
      concentrations among North African and Belgian newborn infants were,
      respectively, 74.0 and 69.6 ng/mL (P=.45). Nationality remained significantly
      associated with C-peptide after adjusting for age and parity. C-peptide, insulin
      like growth factor-I correlated positively with birth weight and remained
      significant factors for birth weight after adjusting for confounders in multiple
      regression. CONCLUSION: These results suggest a link between higher C-peptide
      levels and birth weights among North African neonates in Belgium.

PMID- 14710116
TI  - Penetration of toxic shock syndrome toxin-1 across porcine vaginal mucosa ex
      vivo: permeability characteristics, toxin distribution, and tissue damage.
AB  - OBJECTIVE: The purpose of this study was to evaluate transvaginal penetration of
      toxic shock syndrome toxin-1 and its effects on permeability and tissue integrity
      in vitro with the use of excised porcine vaginal mucosa. STUDY DESIGN:
      Permeability to tritiated water (1 and 10 microg/mL applied toxin) and
      transmucosal flux of (35)S-methionine-labeled toxic shock syndrome toxin-1 (10
      and 20 microg/mL) for up to 12 hours were assessed with the use of a continuous
      flow perfusion system. The location of labeled toxin that penetrated the mucosal
      tissue strata was determined. The integrity of toxin-treated, intact, scalpel
      incised tissue was evaluated histopathologically. RESULTS: Toxic shock syndrome
      toxin-1 caused a non-dose-dependent increase in mucosal permeability and
      traversed the intact mucosa at a low rate without disrupting tissue integrity. In
      incised vaginal mucosa, toxic shock syndrome toxin-1 induced subepithelial
      separation and atrophy that were analogous to clinically relevant vaginal lesions
      that were reported in fatal cases of menstrual toxic shock syndrome. CONCLUSION:
      An in vitro model could be used to demonstrate that toxic shock syndrome toxin-1
      permeates the vaginal mucosa and distributes throughout the tissue. Histologic
      evaluation of tissues that were exposed to toxic shock syndrome toxin-1
      demonstrated lesions that were similar to those lesions that were reported in
      cases of menstrual toxic shock syndrome.

PMID- 14710117
TI  - Four-dimensional ultrasonography of the fetal heart with spatiotemporal image
      correlation.
AB  - OBJECTIVE: This study was undertaken to describe a new technique for the
      examination of the fetal heart using four-dimensional ultrasonography with
      spatiotemporal image correlation (STIC). STUDY DESIGN: Volume data sets of the
      fetal heart were acquired with a new cardiac gating technique (STIC), which uses
      automated transverse and longitudinal sweeps of the anterior chest wall. These
      volumes were obtained from 69 fetuses: 35 normal, 16 with congenital anomalies
      not affecting the cardiovascular system, and 18 with cardiac abnormalities.
      Dynamic multiplanar slicing and surface rendering of cardiac structures were
      performed. To illustrate the STIC technique, two representative volumes from a
      normal fetus were compared with volumes obtained from fetuses with the following
      congenital heart anomalies: atrioventricular septal defect, tricuspid stenosis,
      tricuspid atresia, and interrupted inferior vena cava with abnormal venous
      drainage. RESULTS: Volume datasets obtained with a transverse sweep were utilized
      to demonstrate the cardiac chambers, moderator band, interatrial and
      interventricular septae, atrioventricular valves, pulmonary veins, and outflow
      tracts. With the use of a reference dot to navigate the four-chamber view,
      intracardiac structures could be simultaneously studied in three orthogonal
      planes. The same volume dataset was used for surface rendering of the
      atrioventricular valves. The aortic and ductal arches were best visualized when
      the original plane of acquisition was sagittal. Volumes could be interactively
      manipulated to simultaneously visualize both outflow tracts, in addition to the
      aortic and ductal arches. Novel views of specific structures were generated. For
      example, the location and extent of a ventricular septal defect was imaged in a
      sagittal view of the interventricular septum. Furthermore, surface-rendered
      images of the atrioventricular valves were employed to distinguish between normal
      and pathologic conditions. Representative video clips were posted on the
      Journal's Web site to demonstrate the diagnostic capabilities of this new
      technique. CONCLUSION: Dynamic multiplanar slicing and surface rendering of the
      fetal heart are feasible with STIC technology. One good quality volume dataset,
      obtained from a transverse sweep, can be used to examine the four-chamber view
      and the outflow tracts. This novel method may assist in the evaluation of fetal
      cardiac anatomy.

PMID- 14710118
TI  - The history of cesarean technique.
AB  - Cesarean section has been practiced since ancient times. Unfortunately, no
      ancient medical documents describing the techniques for cesarean section are
      extant. In the early medieval period, cesarean section was usually performed by
      midwives. One of the first explicit instructions in medical literature on
      cesarean technique dates from about 1480 ce from southern Germany. We discuss the
      evolution of cesarean surgical technique and point up the contribution of many
      giants in the field of obstetrics and gynecology, such as Blundell, Frank,
      Harris, Joel-Cohen, Kehrer, Kerr, Lebas, Levret, Maylard, Pfannenstiel, Porro,
      Portes, and Sanger.

PMID- 14710119
TI  - Posterior presentation comments.

PMID- 14710121
TI  - Wishing the WISH cells were pure.

PMID- 14710123
TI  - A change in medical student attitudes of obstetrics-gynecology clerkships toward
      seeking consent for pelvic examinations on an anesthetized patient.

PMID- 14710125
TI  - Low birth weight and prematurely in infertility patients.

PMID- 14710127
TI  - Research on maternal and fetal safety after exposure to antidepressants in utero.

PMID- 14710129
TI  - Base excess during cord occlusion.

PMID- 14710131
TI  - Fetal betamethasone treatment and neonatal outcome in preeclampsia and
      intrauterine growth restriction.

PMID- 14710133
TI  - Midwifery: a philosophy not a function.

PMID- 14710134
TI  - Active management of the third stage of labor: why is it controversial?

PMID- 14710135
TI  - Role of human papilloma virus testing in cervical cancer prevention.
AB  - A clear causal relationship has been established between human papilloma virus
      (HPV) infection and the development of cervical cancer. Genital HPV infection is
      currently the most common sexually transmitted disease worldwide. The recent 2001
      American Society for Colposcopy and Cervical Pathology Consensus Guidelines have
      included HPV testing for management of women with cervical cytological
      abnormalities. Clinicians now face the challenge of deciding when to use HPV
      testing in follow-up of abnormal Pap tests. This article includes updates on HPV,
      cervical cancer screening, and HPV testing technology. Recommendations for
      integration of HPV testing into clinical practice are provided.

PMID- 14710136
TI  - The landscape of caring for women: a narrative study of midwifery practice.
AB  - Our purpose was to expand knowledge on the process and outcomes of midwifery
      care. Narrative analysis was used to interpret stories provided by midwives to
      illustrate their practice and recipients of midwifery care about their
      experience. A purposive sample of 14 midwives and four recipients of midwifery
      care was recruited as a subsample from a prior Delphi study on midwifery
      practice. Three broad themes were identified: 1) the midwife in relationship with
      the woman, 2) orchestration of an environment of care, and 3) the outcomes of
      care, called "life journeys" for the woman and the midwife. The findings are
      discussed from the perspectives of therapeutic landscapes described in cultural
      geography and prior research on midwifery practice. The challenge is to confirm
      the associations between the processes of care identified in these narratives
      with both short- and long-term outcomes in the health of women and their
      families. These appear to go well beyond the usual perinatal measures currently
      used in health care research and hold implications for how care is delivered,
      measured, and evaluated.

PMID- 14710137
TI  - Supporting women in labor: analysis of different types of caregivers.
AB  - Continuous labor support offers multiple benefits for mothers and infants. The
      type of caregiver that is the best support person in labor has not been
      identified. A critical review of the English language literature was conducted to
      describe the current state of knowledge on different types of labor support
      persons. Randomized trials and other published reports were identified from
      relevant databases and hand searches. Studies were reviewed and assessed by using
      a structured format. Eight randomized trials met the selection criteria for
      inclusion in this analysis. These trials investigated untrained and trained lay
      women, female relatives, nurses, lay midwives, and student lay midwives as labor
      support persons. Support by untrained lay women starting in early labor and
      continuing into the postpartum period demonstrates the most consistent beneficial
      effect on childbirth outcomes. However, more randomized controlled trials are
      warranted before firm conclusions may be drawn.

PMID- 14710138
TI  - Building evidence for practice: a pilot study of newborn bulb suctioning at
      birth.
AB  - The purpose of the study was to examine the effects of bulb suctioning on
      healthy, term newborns and the feasibility of conducting a large-scale study of
      this practice. In a randomized, controlled two-group design pilot study, 10
      newborns received oronasopharyngeal bulb suctioning at birth and 10 did not.
      Differences in Apgar scores, heart rates, and oxygen saturation levels were
      determined. Infants were randomized to groups before delivery. The participants
      were 20 term, healthy newborns of uncomplicated pregnancies. Apgar scores, heart
      rates, and oxygen saturation levels in the first 20 minutes of life were the main
      outcome variables. There were no statistically significant differences in Apgar
      scores between groups. Apgar scores at 5 and 10 minutes were 9 or 10 for all
      newborns. Newborns receiving bulb suctioning showed a statistically significant,
      lower heart rate (P=.042) during the first 20 minutes and a significantly higher
      SpO2 level (P=.005) by 15 minutes of age. Although statistically significant,
      these findings were not considered clinically significant because values remained
      within normal parameters.

PMID- 14710139
TI  - Retirement among Florida's certified nurse-midwives: an impending workforce
      crisis.
AB  - An anonymous survey was mailed to 499 CNMs in Florida in May 2001 to examine the
      impact of CNM retirement on the Florida women's health provider workforce and to
      estimate the replacement demand for CNMs. The survey also investigated where
      Florida's CNMs studied midwifery, reasons for choosing education programs,
      reasons for moving to Florida, and causes of underemployment of CNMs. Two hundred
      eighty respondents returned the survey. Thirty-nine percent of respondents
      received their midwifery education in Florida. Eighty-one percent of respondents
      were working as CNMs. From 2010 through 2025, an average of 11 CNMs in Florida
      will reach age 65 each year. These data indicate that retirement will generate
      demand for new CNMs in the next two decades. These data, along with future
      research tracking midwifery education, employment, and retirement, could be used
      to plan program funding, clinical site needs, and legislative support of
      midwifery.

PMID- 14710140
TI  - Clinician perspectives on participation in research.
AB  - Midwifery practice settings offer ideal opportunities to conduct research on
      normal childbearing. Increasing the output of midwifery research would benefit
      midwives, as well as the women they serve. But finding ways to add research
      activities to a busy clinical schedule is a challenge. Factors thought to promote
      clinician participation in research are as follows: perceived relevance of the
      research topic, a relationship with a lead researcher, regular feedback to
      clinicians, minimal impact of a study on usual clinical care, and some level of
      compensation for clinicians who participate in research. Barriers include time
      constraints, lack of research updates and support, and limited research skills of
      clinicians. Joint projects by academic researchers teamed with active clinician
      groups are suggested as one way to move a midwifery research agenda forward.

PMID- 14710141
TI  - Factor V Leiden and contraception.
AB  - Factor V Leiden is the most common genetic cause of primary and recurrent venous
      thromboembolism in women. It is an inherited thrombophilia that results from a
      genetic mutation. A college-aged woman who presented for care and had a positive
      family history of venous thrombosis tested positive for Factor V Leiden.
      Laboratory tests and plans for continuing care are discussed.

PMID- 14710142
TI  - Resources for evidence-based practice, January/February 2004.

PMID- 14710143
TI  - New guidelines for Pap screening and management of results.

PMID- 14710148
TI  - Genital warts.

PMID- 14710149
TI  - Nurse-midwifery week 2003.

PMID- 14710150
TI  - Vaginal birth after previous cesarean section.

PMID- 14710151
TI  - Joint statement: management of the third stage of labour to prevent post-partum
      haemorrhage.

PMID- 14710166
TI  - Paediatric obesity: what do we know and are we doing the right thing?

PMID- 14710152
TI  - Percentage of live births attended by CNMs in the United States, 1989-2001.

PMID- 14710167
TI  - Effect of physical activity on autonomic nervous system function in lean and
      obese children.
AB  - OBJECTIVE: The autonomic nervous system (ANS) is a key factor in the regulation
      of energy balance and body fat storage;however, to what extent the physical
      activity during the childhood years contributes to variations in ANS function is
      still unclear. The present study was designed to investigate the ANS activity in
      lean and obese children, focusing on the differences in physical activity levels.
      SUBJECTS: This study was performed on 1080 school children initially recruited to
      the present study. In all, 24 physically active and 24 inactive obese children (>
      or =120% of the standard body weight) were chosen as samples. Then, 24 lean
      active and 24 lean-inactive children, who were matched individually in age,
      gender, height, and the amount of sports activity, were carefully selected from
      the remaining children. MEASUREMENTS: Physical activity was classified as the
      frequency of participation in after-school sports activities (active; > or =3
      times per week, inactive; nothing). The ANS activities were measured during the
      resting condition by means of heart rate (HR) variability power spectral
      analysis, which enables us to identify separate frequency components, that is,
      low frequency (LF; 0.03-0.15 Hz), reflecting mixed sympathetic (SNS) and
      parasympathetic nervous system (PNS) activity, high frequency (HF; 0.15-0.5 Hz),
      mainly associated with PNS activity, and total power (TP; 0.03-0.5 Hz),
      evaluating the overall ANS activity. The spectral powers were log transformed for
      statistical testing. RESULTS: The lean-active group demonstrated lower resting HR
      as well as significantly higher TP, LF, and HF powers compared to the remaining
      groups. In contrast, the obese-inactive group showed significantly lower TP
      (P<0.05 vs the remaining groups), LF (P<0.05 vs the lean groups), and HF power
      (P<0.05 vs the lean groups), respectively. The obese-active and lean-inactive
      groups were nearly identical in all spectral parameters. The correlation analysis
      revealed that TP among 48 inactive children was significantly and negatively
      associated with the percentage of body fat (r=-0.53, P<0.001); however, such
      correlation among 48 active children was modest (r=-0.33, P=0.02). CONCLUSION:
      Our data suggest that obese children possess reduced sympathetic as well as
      parasympathetic nervous activities as compared to lean children who have similar
      physical activity levels. Such autonomic reduction, associated with the amount of
      body fat in inactive state, might be an etiological factor of onset or
      development of childhood obesity. On the other hand, regular physical activities
      could contribute to enhance the overall ANS activity in both lean and obese
      children. These findings further imply that regular physical activity might be
      effective in preventing and treating obesity beginning in the childhood.

PMID- 14710168
TI  - High protein intake sustains weight maintenance after body weight loss in humans.
AB  - BACKGROUND: A relatively high percentage of energy intake as protein has been
      shown to increase satiety and decrease energy efficiency during overfeeding. AIM:
      To investigate whether addition of protein may improve weight maintenance by
      preventing or limiting weight regain after weight loss of 5-10% in moderately
      obese subjects. DESIGN OF THE STUDY: In a randomized parallel design, 148 male
      and female subjects (age 44.2 +/- 10.1 y; body mass index (BMI) 29.5 +/- 2.5
      kg/m2; body fat 37.2 +/- 5.0%) followed a very low-energy diet (2.1 MJ/day)
      during 4 weeks. For subsequent 3 months weight-maintenance assessment, they were
      stratified according to age, BMI, body weight, restrained eating, and resting
      energy expenditure (REE), and randomized over two groups. Both groups visited the
      University with the same frequency, receiving the same counseling on demand by
      the dietitian. One group (n=73) received 48.2 g/day additional protein to their
      diet. Measurements at baseline, after weight loss, and after 3 months weight
      maintenance were body weight, body composition, metabolic measurements, appetite
      profile, eating attitude, and relevant blood parameters. RESULTS: Changes in body
      mass, waist circumference, REE, respiratory quotient (RQ), total energy
      expenditure (TEE), dietary restraint, fasting blood-glucose, insulin,
      triacylglycerol, leptin, beta-hydroxybutyrate, glycerol, and free fatty acids
      were significant during weight loss and did not differ between groups. During
      weight maintenance, the 'additional-protein group' showed in comparison to the
      nonadditional-protein group 18 vs 15 en% protein intake, a 50% lower body weight
      regain only consisting of fat-free mass, a 50% decreased energy efficiency,
      increased satiety while energy intake did not differ, and a lower increase in
      triacylglycerol and in leptin; REE, RQ, TEE, and increases in other blood
      parameters measured did not differ. CONCLUSION: A 20% higher protein intake, that
      is, 18% of energy vs 15% of energy during weight maintenance after weight loss,
      resulted in a 50% lower body weight regain, only consisting of fat-free mass, and
      related to increased satiety and decreased energy efficiency.

PMID- 14710169
TI  - Within- and between-laboratory precision in the measurement of body volume using
      air displacement plethysmography and its effect on body composition assessment.
AB  - OBJECTIVE: To determine and compare the extent of within- and between-laboratory
      precision in body volume (BV) measurements using air displacement plethysmography
      (ADP), the BOD POD body composition system, and to interpret any such variability
      in terms of body composition estimates. DESIGN: Repeated test procedures of BV
      assessment using the BOD POD ADP were reproduced at two laboratories for the
      estimation of precision, both within and between laboratories. SUBJECTS: In
      total, 30 healthy adult volunteers, 14 men (age, 19-48 y; body mass index (BMI),
      19.7-30.3 kg/m2) and 16 women (age, 19-40 y; BMI, 16.3-35.7 kg/m2), were each
      subjected to two test procedures at both laboratories. Two additional volunteers
      were independently subjected to 10 repeated test procedures at both laboratories.
      MEASUREMENTS: Repeated measurements of BV, uncorrected for the effects of
      isothermal air in the lungs and the surface area artifact, were obtained using
      the BOD POD ADP, with the identical protocol being faithfully applied at both
      laboratories. Uncorrected BV measurements were adjusted to give estimates of
      actual BV that were used to calculate body density (body weight (BWt)/actual BV)
      from which estimates of body composition were derived. The differences between
      repeated BV measurements or body composition estimates were used to assess within
      laboratory precision (repeatability), as standard deviation (SD) and coefficient
      of variation; the differences between measurements reproduced at each laboratory
      were used to determine between-laboratory precision (reproducibility), as bias
      and 95% limits of agreement (from SD of the differences between laboratories).
      RESULTS: The extent of within-laboratory methodological precision for BV
      (uncorrected and actual) was variable according to subject, sample group and
      laboratory conditions (range of SD, 0.04-0.13 l), and was mostly due to within
      individual biological variability (typically 78-99%) rather than to technical
      imprecision. There was a significant (P<0.05) bias between laboratories for the
      10 repeats on the two independent subjects (up to 0.29 l). Although no
      significant bias (P=0.077) was evident for the sample group of 30 volunteers (
      0.05 l), the 95% limits of agreement were considerable (-0.68 to 0.58 l). The
      effects of this variability in BV on body composition were relatively greater:
      for example, within-laboratory precision (SD) for body fat as % BWt was between
      0.56 and 1.34% depending on the subject and laboratory; the bias (-0.59%) was not
      significant between laboratories, but there were large 95% limits of agreement (
      3.67 to 2.50%). CONCLUSION: Within-laboratory precision for each BOD POD
      instrument was reasonably good, but was variable according to the prevailing
      conditions. Although the bias between the two instruments was not significant for
      the BV measurements, implying that they can be used interchangeably for groups of
      similar subjects, the relatively large 95% limits of agreement indicate that
      greater consideration may be needed for assessing individuals with different ADP
      instruments. Therefore, use of a single ADP instrument is apparently preferable
      when assessing individuals on a longitudinal basis.

PMID- 14710170
TI  - Influence of gender, age and BMI on lower limb muscular power output in a large
      population of obese men and women.
AB  - OBJECTIVE: To depict the general trends of muscle anaerobic performance in obese
      subjects within a wide range of age and body weight. DESIGN: Cross-sectional
      study for the measurement of lower limb maximal anaerobic power output with a
      modification of the Margaria stair climbing test in a large population of obese
      subjects of both genders within a wide span of age (18-80 y) and body mass index
      (BMI, 30-68 kg m(-2)). Furthermore, body composition was also determined by
      bioimpedance analysis in a representative subgroup, in order to evaluate the
      relationships between fat-free mass (FFM) and power output. SUBJECTS: A total of
      1298 obese subjects (486 males, 812 females) from an Italian population seeking
      medical support for body weight reduction. Within this sample, a consistent
      subgroup of 193 subjects (59 males, 134 females) was also selected for accessory
      study of body composition. RESULTS: In general, male subjects developed
      significantly higher lower limb power output (W) than female subjects (P<0.001
      0.01), both in absolute terms and per unit body mass. In both genders, W was
      influenced negatively by age (P<0.001) and positively by BMI (P<0.001). While the
      effect of age was similar in both genders, BMI had a different positive effect in
      male and in female subjects, being more definite in male subjects. In the
      subgroup, FFM was found to depend both on age and BMI, in a fashion comparable
      with that displayed by W. The gender-related differences in W disappeared when
      expressed per unit FFM and a significant linear correlation was found between FFM
      and W, both in male and female subjects (R2=0.32-0.51, P<0.001). CONCLUSIONS: The
      lower limb maximal power output is significantly higher in obese male subjects
      than in female subjects, being negatively influenced by age but positively
      related to BMI. Female subjects appear to be at a greater disadvantage for effect
      of obesity, the major motor limitations being suffered by older women with higher
      BMI. These gender differences in age- and BMI-dependent W changes seem to be
      related to changes in FFM in the subgroup in whom body composition was studied.

PMID- 14710171
TI  - Genetics of egg production in Drosophila sechellia.
AB  - Drosophila sechellia, an island endemic that specializes on a single host plant,
      has a lower rate of egg production than its generalist sister species D.
      melanogaster, D. simulans, and D. mauritiana. Earlier work showed that part of
      this difference in egg production was due to a reduction in the number of
      ovarioles in D. sechellia relative to its sister species. Here, I extend this
      earlier work by genetically analyzing the difference in egg production between D.
      sechellia and D. simulans. In all, 10 genetic markers were used in several
      interspecific backcrosses to identify chromosome regions that affected the rate
      of egg production. While previously mapped factors affecting ovariole number
      appear to impact the rate of egg production, new, non-ovariole factors were also
      identified. Overall, the difference in egg production between D. sechellia and D.
      simulans appears to be a polygenic trait. The relationship between these factors
      and genes involved the adaptation of D. sechellia to its host plant is not yet
      clear. The data are consistent with the hypothesis that decline in egg production
      is, in part, a negative pleiotropic effect of genetic changes required for host
      specialization in D. sechellia, although finer-scale genetic analysis of both
      traits is needed to truly test this hypothesis.

PMID- 14710172
TI  - Allelic diversity of S-RNase at the self-incompatibility locus in natural
      flowering cherry populations (Prunus lannesiana var. speciosa).
AB  - In the Rosaceae family, which includes Prunus, gametophytic self-incompatibility
      (GSI) is controlled by a single multiallelic locus (S-locus), and the S-locus
      product expressed in the pistils is a glycoprotein with ribonuclease activity (S
      RNase). Two populations of flowering cherry (Prunus lannesiana var. speciosa),
      located on Hachijo Island in Japan's Izu Islands, were sampled, and S-allele
      diversity was surveyed based on the sequence polymorphism of S-RNase. A total of
      seven S-alleles were cloned and sequenced. The S-RNases of flowering cherry
      showed high homology to those of Prunus cultivars (P. avium and P. dulcis). In
      the phylogenetic tree, the S-RNases of flowering cherry and other Prunus
      cultivars formed a distinct group, but they did not form species-specific
      subgroups. The nucleotide substitution pattern in S-RNases of flowering cherry
      showed no excess of nonsynonymous substitutions relative to synonymous
      substitutions. However, the S-RNases of flowering cherry had a higher Ka/Ks ratio
      than those of other Prunus cultivars, and a subtle heterogeneity in the
      nucleotide substitution rates was observed among the Prunus species. The S
      genotype of each individual was determined by Southern blotting of restriction
      enzyme-digested genomic DNA, using cDNA for S-RNase as a probe. A total of 22 S
      alleles were identified. All individuals examined were heterozygous, as expected
      under GSI. The allele frequencies were, contrary to the expectation under GSI,
      significantly unequal. The two populations studied showed a high degree of
      overlap, with 18 shared alleles. However, the allele frequencies differed
      considerably between the two populations.

PMID- 14710173
TI  - Ethical profits from publishing.

PMID- 14710174
TI  - Are we becoming less disposable?

PMID- 14710175
TI  - Building scientific capacity in developing countries.

PMID- 14710176
TI  - An active life in science. Interview by Holger Breithaupt and Caroline Hadley.

PMID- 14710177
TI  - A cause without a disease.

PMID- 14710178
TI  - The changing identity of the scientist.

PMID- 14710181
TI  - Life in a crowded world.

PMID- 14710182
TI  - Lentiviral transgene vectors.

PMID- 14710183
TI  - Roles of G-protein-coupled receptor dimerization.
AB  - The classical idea that G-protein-coupled receptors (GPCRs) function as monomeric
      entities has been unsettled by the emerging concept of GPCR dimerization. Recent
      findings have indicated not only that many GPCRs exist as homodimers and
      heterodimers, but also that their oligomeric assembly could have important
      functional roles. Several studies have shown that dimerization occurs early after
      biosynthesis, suggesting that it has a primary role in receptor maturation. G
      protein coupling, downstream signalling and regulatory processes such as
      internalization have also been shown to be influenced by the dimeric nature of
      the receptors. In addition to raising fundamental questions about GPCR function,
      the concept of dimerization could be important in the development and screening
      of drugs that act through this receptor class. In particular, the changes in
      ligand-binding and signalling properties that accompany heterodimerization could
      give rise to an unexpected pharmacological diversity that would need to be
      considered.

PMID- 14710184
TI  - Chemotaxis: signalling modules join hands at front and tail.
AB  - Chemotaxis is the result of a refined interplay among various intracellular
      molecules that process spatial and temporal information. Here we present a
      modular scheme of the complex interactions between the front and the back of
      cells that allows them to navigate. First, at the front of the cell, activated
      Rho-type GTPases induce actin polymerization and pseudopod formation. Second,
      phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) is produced in a
      patch at the leading edge, where it binds pleckstrin-homology-domain-containing
      proteins, which enhance actin polymerization and translocation of the pseudopod.
      Third, in Dictyostelium amoebae, a cyclic-GMP-signalling cascade has been
      identified that regulates myosin filament formation in the posterior of the cell,
      thereby inhibiting the formation of lateral pseudopodia that could misdirect the
      cell.

PMID- 14710185
TI  - A test of the CoHR motif associated with meiotic double-strand breaks in
      Saccharomyces cerevisiae.
AB  - Meiotic recombination is not random along chromosomes; rather, there are
      preferred regions for initiation called hotspots. Although the general properties
      of meiotic hotspots are known, the requirements at the DNA sequence level for the
      determination of hotspot activity are still unclear. The sequence of six known
      hotspots in Saccharomyces cerevisiae was compared to identify a common homology
      region (CoHR). They reported that the locations of CoHR sequences correspond to
      mapped double-strand break (DSB) sites along three chromosomes (I, III, VI). We
      report here that a deletion of CoHR at HIS2, a hotspot used to identify the
      motif, has no significant effect on recombination. In the absence of CoHR, DSB
      formation occurs at a high frequency and at the same sequences as in wild-type
      strains. In cases where the deletion of sequences containing the CoHR motif has
      been shown to reduce recombination, we propose that it may be a reflection of the
      location of the deletion, rather than the loss of CoHR, per se.

PMID- 14710186
TI  - Molecular evidence indicating that the yeast PAF complex is required for
      transcription elongation.
AB  - PAF is a five-subunit protein complex composed of Paf1, Cdc73, Leo1, Rtf1 and
      Ctr9, which was purified from yeast in association with RNA polymerase II and
      which is believed to function in transcription elongation. However, no direct
      proof exists for this yet. To assay whether PAF is required in elongation, we
      determined the in vitro transcription-elongation efficiencies of mutant cell
      extracts using a DNA template containing two G-less cassettes. paf1Delta or
      cdc73Delta cell extracts showed reduced transcription-elongation efficiencies (16
      18% of the wild-type levels), whereas leo1Delta and rtf1Delta showed wild-type
      levels. In vivo transcription efficiency was diminished in the four mutants
      analysed, as determined by their abilities to transcribe lacZ. Our work provides
      molecular evidence that PAF has a positive role in transcription elongation and
      is composed of at least two functionally different types of subunits (Paf1-Cdc73
      and Leo1-Rtf1).

PMID- 14710187
TI  - MlaA, a hexameric ATPase linked to the Mre11 complex in archaeal genomes.
AB  - We identify and characterize MlaA, a novel protein, which is found in a conserved
      operon with Mre11 and Rad50 in archaeal genomes. MlaA is fused with Mre11 in
      Methanobacter thermoautotrophicus, suggesting the MlaA is functionally linked to
      the Mre11 complex. MlaA preferentially and cooperatively binds double-stranded
      and secondary structure containing DNA and has double-stranded but not single
      stranded DNA-stimulated ATPase activity. Electron microscopy reveals that MlaA
      forms a 360-kDa hexameric ring structure with a central hole. Our data suggest
      that the archaeal Mre11 complex is associated with a novel hexameric ATPase that
      could be required for the processing of DNA double-stranded breaks and
      recombination intermediates.

PMID- 14710188
TI  - D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific
      phosphorylation and nuclear exclusion of FOXO1a.
AB  - The protein kinase CK1 phosphorylates serine residues that are located close to
      another phosphoserine in the consensus pSer-Xaa-Xaa-Ser. This specificity
      generates regions in its target proteins containing two or more neighbouring
      phosphoserine residues, termed here multisite phosphorylation domains (MPDs). In
      this paper, we demonstrate that D4476 is a potent and rather selective inhibitor
      of CK1 in vitro and in cells. In H4IIE hepatoma cells, D4476 specifically
      inhibits the phosphorylation of endogenous forkhead box transcription factor O1a
      (FOXO1a) on Ser322 and Ser325 within its MPD, without affecting the
      phosphorylation of other sites. Our results indicate that these residues are
      targeted by CK1 in vivo and that the CK1-mediated phosphorylation of the MPD is
      required for accelerated nuclear exclusion of FOXO1a in response to IGF-1 and
      insulin. D4476 is much more potent and specific than IC261 or CKI-7, and is
      therefore the most useful CK1 inhibitor currently available for identifying
      physiological substrates of CK1.

PMID- 14710189
TI  - Adaptation to extreme environments: macromolecular dynamics in bacteria compared
      in vivo by neutron scattering.
AB  - Mean macromolecular dynamics was quantified in vivo by neutron scattering in
      psychrophile, mesophile, thermophile and hyperthermophile bacteria. Root mean
      square atomic fluctuation amplitudes determining macromolecular flexibility were
      found to be similar for each organism at its physiological temperature (
      approximately 1 A in the 0.1 ns timescale). Effective force constants determining
      the mean macromolecular resilience were found to increase with physiological
      temperature from 0.2 N/m for the psychrophiles, which grow at 4 degrees C, to 0.6
      N/m for the hyperthermophiles (85 degrees C), indicating that the increase in
      stabilization free energy is dominated by enthalpic rather than entropic terms.
      Larger resilience allows macromolecular stability at high temperatures, while
      maintaining flexibility within acceptable limits for biological activity.

PMID- 14710190
TI  - Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian
      family with scattered phylogenetic distribution.
AB  - While the genome sequence and gene content are available for an increasing number
      of organisms, eukaryotic selenoproteins remain poorly characterized. The dual
      role of the UGA codon confounds the identification of novel selenoprotein genes.
      Here, we describe a comparative genomics approach that relies on the genome-wide
      prediction of genes with in-frame TGA codons, and the subsequent comparison of
      predictions from different genomes, wherein conservation in regions flanking the
      TGA codon suggests selenocysteine coding function. Application of this method to
      human and fugu genomes identified a novel selenoprotein family, named SelU, in
      the puffer fish. The selenocysteine-containing form also occurred in other fish,
      chicken, sea urchin, green algae and diatoms. In contrast, mammals, worms and
      land plants contained cysteine homologues. We demonstrated selenium incorporation
      into chicken SelU and characterized the SelU expression pattern in zebrafish
      embryos. Our data indicate a scattered evolutionary distribution of
      selenoproteins in eukaryotes, and suggest that, contrary to the picture emerging
      from data available so far, other taxa-specific selenoproteins probably exist.

PMID- 14710191
TI  - Vegfc is required for vascular development and endoderm morphogenesis in
      zebrafish.
AB  - During embryogenesis, complex morphogenetic events lead endodermal cells to
      coalesce at the midline and form the primitive gut tube and associated organs.
      While several genes have recently been implicated in endoderm differentiation, we
      know little about the genes that regulate endodermal morphogenesis. Here, we show
      that vascular endothelial growth factor C (Vegfc), an angiogenic as well as a
      lymphangiogenic factor, is unexpectedly involved in this process in zebrafish.
      Reducing Vegfc levels using morpholino antisense oligonucleotides, or through
      overexpression of a soluble form of the VEGFC receptor, VEGFR-3, affects the
      coalescence of endodermal cells in the anterior midline, leading to the formation
      of a forked gut tube and the duplication of the liver and pancreatic buds.
      Further analyses indicate that Vegfc is additionally required for the initial
      formation of the dorsal endoderm. We also demonstrate that Vegfc is required for
      vasculogenesis as well as angiogenesis in the zebrafish embryo. These data argue
      for a requirement of Vegfc in the developing vasculature and, more surprisingly,
      implicate Vegfc signalling in two distinct steps during endoderm development,
      first during the initial differentiation of the dorsal endoderm, and second in
      the coalescence of the anterior endoderm to the midline.

PMID- 14710192
TI  - A mechanism for the activation of the Na/H exchanger NHE-1 by cytoplasmic
      acidification and mitogens.
AB  - Eukaryotic cells constantly have to fight against internal acidification. In
      mammals, this task is mainly performed by the ubiquitously expressed
      electroneutral Na(+)/H(+) exchanger NHE-1, which activates in a cooperative
      manner when cells become acidic. Despite its biological importance, the mechanism
      of this activation is still poorly understood, the most commonly accepted
      hypothesis being the existence of a proton-sensor site on the internal face of
      the transporter. This work uncovers mutations that lead to a nonallosteric form
      of the exchanger and demonstrates that NHE-1 activation is best described by a
      Monod-Wyman-Changeux concerted mechanism for a dimeric transporter. During
      intracellular acidification, a low-affinity form of NHE-1 is converted into a
      form possessing a higher affinity for intracellular protons, with no requirement
      for an additional proton-sensor site on the protein. This new mechanism also
      explains the activation of the exchanger by growth signals, which shift the
      equilibrium towards the high-affinity form.

PMID- 14710193
TI  - Cyclin B degradation leads to NuMA release from dynein/dynactin and from spindle
      poles.
AB  - The protein NuMA localizes to mitotic spindle poles where it contributes to the
      organization of microtubules. In this study, we demonstrate that NuMA loses its
      stable association with the spindle poles after anaphase onset. Using extracts
      from Xenopus laevis eggs, we show that NuMA is dephosphorylated in anaphase and
      released from dynein and dynactin. In the presence of a nondegradable form of
      cyclin B (Delta90), NuMA remains phosphorylated and associated with dynein and
      dynactin, and remains localized to stable spindle poles that fail to disassemble
      at the end of mitosis. Inhibition of NuMA or dynein allows completion of mitosis,
      despite inducing spindle pole abnormalities. We propose that NuMA functions early
      in mitosis during the formation of spindle poles, but is released from the
      spindle after anaphase, to allow spindle disassembly and remodelling of the
      microtubule network.

PMID- 14710194
TI  - Involvement of the intermediate filament protein cytokeratin-18 in actin pedestal
      formation during EPEC infection.
AB  - While remaining extracellular, enteropathogenic Escherichia coli (EPEC) establish
      direct links with the cytoskeleton of the target epithelial cell leading to the
      formation of actin-rich pedestals underneath attached bacteria. The translocated
      adaptor protein Tir forms the transmembrane bridge between the cytoskeleton and
      the bacterium; the extracellular domain of Tir functions as a receptor for the
      bacterial adhesin intimin, while the intracellular amino and carboxy termini
      interact with a number of focal adhesion and other cytoskeletal proteins; and
      recruitment of some is dependent on phosphorylation of Tyr 474. Using Tir as bait
      and HeLa cell cDNA library as prey in a yeast two-hybrid screen, we identified
      cytokeratin 18 as a novel Tir partner protein. Cytokeratin 18 is recruited to the
      EPEC-induced pedestal and has a direct role in actin accretion and cytoskeleton
      reorganization. This study is the first to implicate intermediate filaments in
      microfilament reorganization following EPEC infection.

PMID- 14710195
TI  - Distinct molecular phenotypes in bovine prion diseases.
AB  - Bovine spongiform encephalopathy (BSE) in cattle, the most likely cause of
      variant Creutzfeldt-Jakob disease in humans, is thought to be caused by a unique
      infectious agent, with stable features, even when transmitted to other species.
      Here, we show the existence of an atypical molecular phenotype among cattle
      diagnosed with BSE in France. Following western blot analysis, three cases showed
      unusual features of the electrophoretic profiles of the protease-resistant prion
      protein (PrP(res)) accumulating in the brain. The PrP(res) patterns were similar
      in these three atypical cases, showing a higher molecular mass of unglycosylated
      PrP(res) and strong labelling by P4 monoclonal antibody compared to 55 typical
      BSE cases. This finding suggests either some phenotypic modifications of PrP(res)
      following infection by the BSE agent or the existence of alternative origins of
      such diseases in cattle.

PMID- 14710196
TI  - Protein kinase-independent activation of CFTR by phosphatidylinositol phosphates.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride
      channel that is expressed in many epithelia and in the heart. Phosphorylation of
      CFTR by protein kinases is thought to be an absolute prerequisite for the opening
      of CFTR channels. In addition, nucleoside triphosphates were shown to regulate
      the opening of phosphorylated CFTR. Here, we report that phosphatidylinositol 4,5
      bisphosphate (PIP(2)) activates human CFTR, resulting in ATP responsiveness of
      PIP(2)-treated CFTR. PIP(2) alone is not sufficient to open CFTR, but ATP opens
      nonphosphorylated CFTR after application of PIP(2). The effect of PIP(2) is
      independent of protein kinases, as PIP(2) activates CFTR in the complete absence
      of Mg. Phosphatidylinositol and phosphatidylinositol monophosphate activate CFTR
      less efficiently than PIP(2). PIP(2) application to phosphorylated CFTR may
      inhibit the CFTR chloride current. We suggest that regulation of CFTR by PIP(2)
      is a previously unrecognized, alternative mechanism to control chloride
      conductance.

PMID- 14710197
TI  - Angiogenesis inhibitors in clinical development; where are we now and where are
      we going?
AB  - Angiogenesis is crucial for tumour growth and the formation of metastases.
      Various classes of angiogenesis inhibitors that are each able to inhibit one of
      the various steps of this complex process can be distinguished. Results from
      clinical studies with these agents are summarised. In general, it has been shown
      that most angiogenesis inhibitors can be safely administered, but that tumour
      regressions are rare. Combining angiogenesis inhibitors with cytotoxic
      chemotherapy can enhance anticancer activity. Recently, some promising data with
      regard to clinical efficacy have been presented. While performing clinical
      studies with angiogenesis inhibitors, defining biological activity is crucial,
      but thus far no validated techniques are available. It is conceivable that in the
      near future various classes of angiogenesis inhibitors will be combined in an
      attempt to further improve antiangiogenic and anticancer activity.

PMID- 14710198
TI  - Cancer pharmacogenetics.
AB  - The large number of active combination chemotherapy regimens for most cancers has
      led to the need for better information to guide the 'standard' treatment for each
      patient. In an attempt to individualise therapy, pharmacogenetics and
      pharmacogenomics (a polygenic approach to pharmacogenetic studies) encompass the
      search for answers to the hereditary basis for interindividual differences in
      drug response. This review will focus on the results of studies assessing the
      effects of polymorphisms in drug-metabolising enzymes and drug targets on the
      toxicity and response to commonly used chemotherapy drugs. In addition, the need
      for polygenic pharmacogenomic strategies to identify patients at risk for adverse
      drug reactions will be highlighted.

PMID- 14710199
TI  - Cancer treatment with kinase inhibitors: what have we learnt from imatinib?
AB  - Over the past few years, a number of anticancer drugs have been developed that
      specifically target kinases known to be oncogenic. The leading drug in this area
      is imatinib mesylate, which targets ABL, KIT and PDGFR. It has been remarkably
      effective in the treatment of chronic myeloid leukaemia, although resistance
      remains a significant problem. From the imatinib experience in this setting, we
      present some principles of kinase inhibition that may have more general
      applicability in targeted anticancer therapy. It is clear that the identification
      of appropriate targets (activated kinases) and monitoring levels of response (to
      recognise emerging resistance) are essential to optimise clinical management.

PMID- 14710200
TI  - First-line endocrine treatment of breast cancer: aromatase inhibitor or
      antioestrogen?
AB  - Until recently, endocrine therapy for breast cancer was relatively simple. If the
      tumour expressed hormone receptors, regardless of stage and age, tamoxifen was
      indicated. While this largely remains the case for premenopausal women, clinical
      trials in postmenopausal women have broadened our choice to include one of three
      selective aromatase inhibitors (AIs), the nonsteroidal agents anastrozole or
      letrozole and the steroidal agent exemestane. Comparative data concerning the
      efficacy, toxicity, tolerability and cost of AI vs tamoxifen continues to evolve
      with over 40 000 women slated to be involved in clinical trials. Currently,
      tamoxifen remains an appropriate choice for adjuvant treatment, and will remain
      so unless a clear survival advantage emerges for adjuvant AI therapy. However,
      anastrozole is widely seen as a useful alternative, with particular merit for
      patients prone to the development of serious tamoxifen side effects. For
      endocrine therapy naive advanced disease, several trials have provided evidence
      that a nonsteroidal AI has replaced tamoxifen as optimal treatment. In the
      neoadjuvant setting, letrozole was also more effective than tamoxifen, both in
      terms of response rates and the incidence of breast-conserving surgery, and so AI
      therefore also dominates this evolving indication. The ongoing adjuvant clinical
      trials ask all the relevant questions regarding tamoxifen and AI in combination,
      sequence and duration, except for 5 years of an AI vs a longer period. For both
      the advanced and early-stage disease, resistance remains the key obstacle to
      overcome, and trials that combine endocrine agents with signal transduction
      inhibitors such as HER1 and HER2 kinase inhibitors, farnesyl transferase
      inhibitors, mTOR inhibitors as well as COX2 inhibitors are being developed in a
      concerted attempt to address this problem.

PMID- 14710201
TI  - Breast cancer treatment in clinical practice compared to best evidence and
      practice guidelines.
AB  - There is sparse evidence on community practice patterns in treating women with
      breast cancer. This study compared care of women with breast cancer with evidence
      from meta-analyses and US National Comprehensive Cancer Network (NCCN) clinical
      guidelines. Records of 4395 women with breast cancer were abstracted from
      practices of 19 surgeon oncologists in six specialty practices in the
      Philadelphia region during 1995-1999. Patients were followed through December
      2001. Low-frequency data were obtained on all patients. All other data were from
      a random sample of 464 women, minimum of 50 patients per practice. Actual care
      provided was compared to NCCN guidelines and results of meta-analyses. Fewer than
      half the women received treatments reflecting meta-analysis results or NCCN
      guidelines, by disease stage/TNM status. Adherence to either standard varied from
      0% for LCIS to 87% for stages IIA or IIB node positive. There are multiple
      interactive reasons for low adherence to guidelines or meta-analyses results,
      including insufficient health system supports to clinicians, inadequate
      organisation and delivery systems and ineffective continuing medical education.
      The paucity of written information from patient records on physician/patient
      interactions limits the understanding of treatment decisions.

PMID- 14710202
TI  - Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as
      first-line chemotherapy in metastatic breast cancer.
AB  - In this phase II, multicentre trial, patients with metastatic breast cancer (MBC)
      were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET).
      The primary objective of this study was to determine the tolerability and
      activity in terms of complete responce (CR) and overall response rate of the GET
      combination in this patient population. Patients with no prior treatment for MBC,
      and at least one bidimensionally measurable lesion received gemcitabine 1000 mg
      m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin
      i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1,
      every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were
      enrolled from seven Italian institutions. A total of 297 chemotherapy courses
      were administered with a median of six cycles patient(-1) (range 1-8). Seven
      patients (15%) obtained CR and 27 patients (56%) had partial responce, for an
      overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of
      23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months
      (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main
      haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in
      62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and
      well tolerated as first-line chemotherapy for MBC.

PMID- 14710203
TI  - Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane
      pretreated patients with HER2-overexpressing metastatic breast cancer.
AB  - Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has
      been shown in vitro and in vivo. In previous experiences, weekly administration
      of trastuzumab and paclitaxel has shown significant activity in metastatic breast
      cancer. In this phase II study, we evaluated the activity and the toxicity of
      this weekly regimen in anthracycline- and taxane-pretreated patients with HER2
      overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25
      patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by
      2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion
      week(-1)). The treatment was planned to continue until disease progression or
      prohibitive toxicity; in patients with responsive or stable disease, after 6
      months of therapy, the decision to stop paclitaxel while continuing weekly
      trastuzumab was left to the physicians' judgement. At the median follow-up of
      19.6 months (range 9.2-38.1), all patients are evaluable for response and
      toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial
      responses (PR), four (16%) stable diseases and seven (28%) disease progressions.
      The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of
      response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6
      months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever
      and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was
      recorded in one patient (4%). Two patients (8%) came off study for grade 3
      cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had
      already received anthracyclines and taxanes. Onycholysis grade 2 was observed in
      five patients (20%). These results confirm that weekly administration of
      trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated
      metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions
      grade 3 were observed (8%), we recommend that cardiac function should be
      monitored in these patients.

PMID- 14710204
TI  - A randomised controlled trial of a psychoeducational intervention for women at
      increased risk of breast cancer.
AB  - This study aimed to compare the impact of two versions of a psychoeducational
      written intervention on cancer worry and objective knowledge of breast cancer
      risk-related topics in women who had been living with an increased risk of
      familial breast cancer for several years. Participants were randomised to three
      conditions: scientific and psychosocial information pack (Group 1), scientific
      information pack only (Group 2) or standard care control (Group 3). They
      completed postal questionnaires at baseline (n=163) and 4 weeks (n=151). As
      predicted, there was a significant decrease in cancer worry for Group 1, but not
      Group 2. Objective knowledge significantly improved for both Group 1 and Group 2
      as expected, but not Group 3. However, there was an unpredicted decline in cancer
      worry for Group 3. This study supports the value of a scientific and psychosocial
      information pack in providing up-to-date information related to familial risk of
      breast cancer for long-term attendees of a familial breast cancer clinic. Further
      research is warranted to determine how the information pack could be incorporated
      into the existing clinical service, thus providing these women with the type of
      ongoing psychosocial support that many familial breast cancer clinics are
      currently lacking.

PMID- 14710205
TI  - Radiation sterilisation of cultured human brain tumour cells for clinical immune
      tumour therapy.
AB  - The aim is to investigate the radiosensitivity of noninfected cultured human
      glioma cells to ascertain that intracutaneously administered cells are viable
      enough to produce interferon-gamma but not able to proliferate. Cell cultures
      were established from five patients undergoing brain tumour surgery. By
      karyotyping, we found four malignant (three glioblastoma multiforme (GBM), one
      giant cell glioma) and one normal. The cells were irradiated with (137)Cs-gamma
      rays at absorbed dose levels of 0, 20, 40, 60, 80, 100 and 120 Gy. The fraction
      of viable cells was examined by MTT incorporation assay. The average of the data
      obtained from three GBM cell cultures was fitted to an exponential model. The
      parameters were: extrapolation number n=0.85+/-0.10, mean lethal dose D(0)=12.4+/
      3.2 Gy and an additional uncertainty parameter deltaS=0.14+/-0.03. By setting
      deltaS=0, the corresponding values of the parameters were n=0.86+/-0.16 and
      D(0)=30.0+/-8.1 Gy. The rate of proliferation was examined by (3)H-thymidine
      incorporation. The average of the proliferation data obtained from three GBM cell
      cultures was fitted to an exponential model yielding n=0.943+/-0.005 and
      D(0)=5.8+/-0.5 Gy for deltaS=0.057+/-0.005, and by setting deltaS=0, n=1.00+/
      0.02 and D(0)=8.4+/-1.6 Gy. No outgrowth of plated cells was observed after 4
      weeks at an absorbed dose of 100 Gy. This absorbed dose is recommended for
      irradiation of 2 x 10(6) glioma cells used for clinical immunisation.

PMID- 14710206
TI  - Bilateral germ-cell tumours: 22-year experience at the Institut Gustave Roussy.
AB  - The aim of this study was to describe the incidence, clinical and histological
      characteristics, treatment and long-term follow-up of bilateral germ-cell tumours
      (BGCT) of the testis in order to determine in what respects they differ
      significantly from unilateral germ-cell tumours. In all, 31 patients with BGCT
      had metachronous tumours and 14 had synchronous tumours. Among the metachronous
      tumours, 61% occurred more than 5 years after the first tumour. The overall
      incidence of BGCT in patients with testicular germ-cell tumours (TGCT) was 1.9%.
      The incidence was 3.2% in patients presenting with a seminoma and 1.4 % in
      patients presenting with a nonseminomatous germ-cell tumour (NSGCT). Patients
      under 30 years of age at the time of the initial diagnosis had a higher incidence
      of bilateral tumours compared with older men. The outcome of BGCT was excellent.
      A high association was found between BGCT, sterility and suspected genetic risk
      factors for TGCT. These results argue against a systematic contralateral biopsy
      at diagnosis of first TGCT in all patients, but emphasise the importance of
      patient education and of the need to better identify patients at risk for a
      second TGCT. Therapeutic indications for synchronous BGCT, including conservative
      treatment, need to be better defined.

PMID- 14710207
TI  - Estimation of glomerular filtration rate in paediatric cancer patients using 51CR
      EDTA population pharmacokinetics.
AB  - Estimation of glomerular filtration rate (GFR) using the clearance of chromium 51
      EDTA ((51)Cr-EDTA) (or other radiolabelled isotopes) is reliable, but invasive
      and not always practicable. Mathematical models have been devised for estimating
      GFR using readily obtainable patient characteristics. Unfortunately, these models
      were developed using various patient populations and may not provide the optimal
      prediction of GFR in children with cancer. The current study uses population
      pharmacokinetics to determine the relationship between (51)Cr-EDTA clearance, and
      patient covariates in 50 paediatric cancer patients. These models were validated
      using a separate group of 43 children and were compared with previously published
      models of renal function. Body size was the major determinant of (51)Cr-EDTA
      clearance and inclusion of weight or surface area reduced the residual
      variability between individuals (coefficient of variation) from 61 to 32%. Serum
      creatinine was the only other parameter that significantly improved the model.
      Mean percentage error values of -5.0 and -1.1% were observed for models including
      weight alone or weight and creatinine, respectively, with precision estimates of
      21.7 and 20.0%. These simple additive models provide a more rationale approach
      than the use of complex formulae, involving additional parameters, to predict
      renal function.

PMID- 14710209
TI  - Definitive chemoradiation in patients with inoperable oesophageal carcinoma.
AB  - We performed a retrospective study of 90 consecutive cases with inoperable
      carcinoma of the oesophagus treated with definitive chemoradiation at a single
      cancer centre between 1995 and 2002. For the last 4 years, 73 patients have
      received therapy according to an agreed protocol. This outpatient-based regimen
      involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50
      Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks.
      Cisplatin 60 mg m(-2) day(-1) is given every 3 weeks together with continuous
      infusional 5-fluorouracil 300 mg m(-2) day(-1), reduced to 225 mg m(-2) day(-1)
      during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4
      toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned
      chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51%
      (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage,
      particularly T4 disease, was associated with a worse prognosis. Patients
      considered not suitable for surgery for reasons other than their disease, mainly
      co-morbidity, had a significantly better outcome, median survival 40 (26, >96)
      months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively
      (P<0.001). This schedule is a feasible, tolerable and effective treatment for
      patients with oesophageal cancer considered unsuitable for surgery.

PMID- 14710208
TI  - Phase II study of viscum fraxini-2 in patients with advanced hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide.
      Although a wide range of therapeutic options is available, the efficacy of these
      methods and the prognosis of patients with HCC remain very poor. This study was
      conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients
      with chemotherapy-naive, advanced hepatocellular carcinoma. 23 patients with
      unrespectable HCC who had received no prior systemic chemotherapy with
      objectively measurable tumors were enrolled on this study. The mistletoe
      preparation for the study is an aqueous injectable solution. It contains one
      milliliter of viscum fraxini in dilution stage-2 (15 mg extract of 20 mg
      mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate,
      ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules.
      2 ampoules of viscum fraxini-2 were administered subcutaneously once weekly. As
      assessed by conventional imaging criteria, 3 (13.1%) patients have achieved
      complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%)
      had progressive disease while 9 (39.1%) patients didn't have evaluation of
      response due to early death. The median overall survival time for all patients
      was 5 months (range 2-38 months), for those who achieved a CR was 29 months
      (range 12-38 months) and, for those who achieved a PR was 6.5 months (range 6-7
      months). The median progression free survival for all patients was 2 months
      (range 1-38 months), for those who achieved a CR, it was 29 months (range 8-38
      months) and for those who achieved a partial response, it was 5 months (range 4-6
      months). No hematologic toxicity has been encountered. The spectrum of non
      hematologic toxicity was mild. The WHO toxicity criteria grade 3-4 were 34.8%
      drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of
      injection. No drug related discontinuation or toxic deaths have occurred. Viscum
      fraxini-2 seems to be particularly promising in patients with advanced HCC, it
      shows antitumor activity and low toxicity profile. Further studies in combination
      with other active agents are clearly warranted.

PMID- 14710210
TI  - The effects of transdermal and oral oestrogen replacement therapy on colorectal
      cancer risk in postmenopausal women.
AB  - The aim of this study was to examine the effects of oral and transdermal
      oestrogen replacement therapy on the risk of colorectal cancer. Data from a
      nested case-control study, designed to investigate the effect of hormone
      replacement therapy (HRT) on colorectal cancer were analysed. New cases of
      colorectal cancer, diagnosed between 1992 and mid-1998 (N=1197), were identified
      using the Saskatchewan Cancer Agency cancer registry. Women >/=50 years of age,
      eligible for coverage by the Saskatchewan Prescription Drug Plan, were included
      in the study. Four controls per case were age matched to cases, using incidence
      density sampling. The outpatient prescription drug plan database was used to
      ascertain oestrogen prescriptions. Women were classified according to history of
      transdermal (TDE) and oral (OE) oestrogen use. Conditional logistic regression
      was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
      Compared with women who had never used HRT, ORs for <3 and >/=3 years of TDE use
      and colorectal cancer were 0.69 (95% CI: 0.43-1.10) and 0.33 (95% CI: 0.12-0.95),
      and for OE use were 0.90 (95% CI: 0.73-1.01) and 0.75 (95% CI: 0.60-0.93),
      respectively. The risk reduction for colorectal cancer with TDE may be greater in
      magnitude than that which has been reported for oral HRT.

PMID- 14710211
TI  - Efficacy and tolerability of gefitinib in pretreated elderly patients with
      advanced non-small-cell lung cancer (NSCLC).
AB  - The activity and toxicity profile of gefitinib in non-small cell lung cancer
      (NSCLC) patients aged 70 years or older has been only partially evaluated. The
      aim of this study was to evaluate the response rate and safety of gefitinib in
      elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and
      with at least one measurable lesion received gefitinib at the daily dose of 250
      mg until disease progression, unacceptable toxicity or refusal. From August 2001
      to May 2003, 40 consecutive elderly patients have been enrolled onto the study in
      three Italian institutions. We observed one complete (2.5%) and one partial
      response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months,
      including six patients (15%) who had disease stabilisation of 6 months or longer,
      for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median
      duration of response was 4.4 months (range 1.7-9.2). The side effects were
      generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea
      occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring
      hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and
      acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in
      elderly pretreated NSCLC patients. The disease-control rate achieved suggests
      that this drug could represent a valid option in the management of this
      unfavourable subgroup of patients.

PMID- 14710212
TI  - Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in
      advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study
      (WJTOG9803).
AB  - Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well
      tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC).
      A randomised phase II study compared their efficacy and toxicity in 108 patients
      with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2)
      and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8
      and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response
      rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2
      year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and
      25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for
      DI, respectively. The progression-free survival time was 20 weeks (95% confidence
      interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with
      DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia
      (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and
      vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI
      (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion,
      although the DI and DC regimens had different toxicity profiles, there was no
      significant difference in survival.

PMID- 14710213
TI  - Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic
      review and meta-analysis.
AB  - Animal and laboratory studies suggest that regular use of nonsteroidal anti
      inflammatory drugs (NSAIDs) may reduce prostate cancer risk. To assess this
      association, we conducted a systematic review and meta-analysis of observational
      studies published before January 2003. We derived summary odds ratios (ORs) using
      both fixed and random effects models and performed subgroup analyses to explore
      the possible sources of heterogeneity between combined studies. We identified 12
      reports (five retrospective and seven prospective studies). Most studies of
      aspirin use reported inverse associations, but only two were statistically
      significant. The summary OR for the association between aspirin use and prostate
      cancer was 0.9 (95% confidence interval: 0.82-0.99; test of homogeneity P=0.32),
      and varied from 1.0 for retrospective studies to 0.85 for prospective studies.
      Studies that measured exposure to a mixture of NSAIDs were less consistent. These
      results indicate an inverse association between aspirin use and prostate cancer
      risk. The current epidemiological evidence and, in particular, the strong and
      consistent laboratory evidence underline the need for additional epidemiological
      studies to confirm the direction and magnitude of the association.

PMID- 14710215
TI  - Effects of a 105 hours psychological training program on attitudes, communication
      skills and occupational stress in oncology: a randomised study.
AB  - There is today a wide consensus regarding the need to improve communication
      skills (CS) of health-care professionals (HCPs) dealing with cancer patients.
      Psychological training programs (PTPs) may be useful to acquire the needed CS.
      Testing the efficacy of PTP will allow to define their optimal content. The
      present study was designed to assess the impact of a PTP on HCP stress, attitudes
      and CS, and on HCP and patients' satisfaction with HCP communication skills in a
      randomised study. A total of 115 oncology nurses were randomly assigned to a 105
      h PTP or to a waiting list. Stress was assessed with the Nursing Stress Scale,
      attitudes with a Semantic Differential Questionnaire, CS used during one
      simulated and one actual patient interview with the Cancer Research Campaign
      Workshop Evaluation Manual, and satisfaction with the nurses' CS with a
      questionnaire completed by the patients and the nurses. Trained (TG) and control
      (CG) groups were compared at baseline, after 3 months (just following training
      for TG) and after 6 months (3 months after the end of training for TG). Compared
      to controls, trained nurses reported positive changes on their stress levels
      (P</=0.05) and on their attitudes (P</=0.05). Positive training effects were
      found on CS used during the simulated interview: a significant increase in
      facilitative behaviours (open questions: P</=0.001; evaluative functions:
      P</=0.05) and a significant decrease in inhibitory behaviours (inappropriate
      information: P</=0.01; false reassurance: P</=0.05). Less positive training
      effects were found regarding interviews with a cancer patient: a significant
      increase in educated guesses (P</=0.001) was noticed. No training effect was
      observed on nurses' satisfaction levels, but a positive training effect was found
      on patients' satisfaction levels (P</=0.01). Although results outline PTP
      efficacy, they indicate the need to design PTP, amplifying the transfer of
      learned CS to clinical practice.

PMID- 14710214
TI  - Randomized Phase II trial assessing estramustine and vinblastine combination
      chemotherapy vs estramustine alone in patients with progressive hormone-escaped
      metastatic prostate cancer.
AB  - Based on the results of combined data from three North American Phase II studies,
      a randomised Phase II study in the same patient population was performed, using
      combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL)
      in hormone refractory prostate cancer patients. In all, 92 patients were
      randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral
      EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by
      2 weeks rest). The end points were toxicity and PSA response in both groups, with
      the option to continue the trial as a Phase III study with time to progression
      and survival as end points, if sufficient responses were observed. Toxicity was
      unexpectedly high in both treatment arms and led to treatment withdrawal or
      refusal in 49% of all patients, predominantly already during the first treatment
      cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA
      progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks,
      and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms,
      respectively. There was no correlation between PSA response and survival. While
      the PSA response in the patients tested was less than half that recorded in the
      North American studies, the toxicity of EMP monotherapy or in combination with
      VBL was much higher than expected. Further research on more effective and less
      toxic treatment strategies for hormone refractory prostate cancer is mandatory.

PMID- 14710216
TI  - Urinary endogenous sex hormone levels in postmenopausal women after caloric
      restriction in young adulthood.
AB  - We investigated whether the 1944-1945 Dutch famine has affected postmenopausal
      sex hormone concentrations with data from 163 women (young adults during the
      famine). Urinary sex hormone concentrations showed modest elevations with
      increasing famine exposure. Effects were absent in parous women, but more
      pronounced in women who had never given birth.

PMID- 14710217
TI  - Nutrition, lifestyle and colorectal cancer incidence: a prospective investigation
      of 10998 vegetarians and non-vegetarians in the United Kingdom.
AB  - In a cohort of 10 998 men and women, 95 incident cases of colorectal cancer were
      recorded after 17 years. Risk increased in association with smoking, alcohol, and
      white bread consumption, and decreased with frequent consumption of fruit. The
      relative risk in vegetarians compared with nonvegetarians was 0.85 (95% CI: 0.55
      1.32).

PMID- 14710218
TI  - Intakes of plant foods, fibre and fat and risk of breast cancer--a prospective
      study in the Malmo Diet and Cancer cohort.
AB  - The objective of this study was to investigate prospectively the associations
      between intakes of plant foods, fibre and relative fat and risk of breast cancer
      in a subsample of 11 726 postmenopausal women in the Malmo Diet and Cancer
      cohort. Data were obtained by an interview-based diet history method, a
      structured questionnaire, anthropometrical measurements and national and regional
      cancer registries. During 89 602 person-years of follow-up, 342 incident cases
      were documented. Cox regression analysis examined breast cancer risks adjusted
      for potential confounders. High fibre intakes were associated with a lower risk
      of postmenopausal breast cancer, incidence rate ratio=0.58, 95% CI: 0.40, 0.84,
      for the highest quintile of fibre intake compared to the lowest quintile. The
      combination high fibre-low fat had the lowest risk when examining the effect in
      each cell of cross-classified tertiles of fibre and fat intakes. An interaction
      (P=0.049) was found between fibre- and fat-tertiles. There was no significant
      association between breast cancer risk and intakes of any of the plant food
      subgroups. These findings support the hypothesis that a dietary pattern
      characterised by high fibre and low fat intakes is associated with a lower risk
      of postmenopausal breast cancer.

PMID- 14710219
TI  - Salt and salted food intake and subsequent risk of gastric cancer among middle
      aged Japanese men and women.
AB  - Evidence on the association between salt intake and gastric cancer is sparse,
      especially in prospective studies. We conducted a population-based prospective
      study in Japan, where the majority of men has been infected with Helicobacter
      pylori. A total of 18 684 men and 20 381 women aged 40-59 years who reported
      their dietary habits and did not report any serious disease at baseline were
      followed from 1990 to 2001. A total of 486 cases, 358 men and 128 women, with
      histologically confirmed gastric cancer were documented among them. The quintile
      category of salt intake was dose-dependently associated with gastric cancer risk
      in men after adjusting for potential confounding factors (P for trend <0.001),
      while a trend was not clear in women (P for trend=0.48). Although stratification
      by study area, with varied salt intake and gastric cancer incidence, attenuated
      the observed clear associations with salt and salted foods, the frequency
      categories of highly salted foods such as salted fish roe and salted fish
      preserves were strongly associated with the risk in both sexes. Restriction of
      salt and salted food intake is a practical strategy to prevent gastric cancer in
      areas with high risk.

PMID- 14710220
TI  - A nested case-control study of stomach cancer in relation to green tea
      consumption in Japan.
AB  - To evaluate whether green tea consumption provides protection against stomach
      cancer, the relative risks (RRs) were calculated in the Japan Collaborative Study
      for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare
      (JACC Study). The study was based on 157 incident cases and 285 controls aged 40
      79 years. Cox proportional hazards regression analysis was used to estimate the
      RRs for stomach cancer. It was found that green tea consumption had no protective
      effect against stomach cancer. After adjustment for age, smoking status, H.
      pylori infection, history of peptic ulcer, and family history of stomach cancer
      along with certain dietary elements, the risks associated with drinking one or
      two, three or four, five to nine, and 10 or more cups of green tea per day,
      relative to those of drinking less than one cup per day, were 1.3 (95% confidence
      interval (CI): 0.6-2.8), 1.0 (95% CI: 0.5-1.9), 0.8 (95% CI: 0.4-1.6), and 1.2
      (95% CI: 0.6-2.5), respectively (P for trend=0.899). We found no inverse
      association between green tea consumption and the risk of stomach cancer.

PMID- 14710221
TI  - Infectious diseases in the first year of life, perinatal characteristics and
      childhood acute leukaemia.
AB  - The objective of the present study was to investigate the role of early common
      infections and perinatal characteristics in the aetiology of childhood common
      leukaemia. A case-control study was conducted from 1995 to 1998 in France, and
      included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic
      leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched
      with 567 population-based controls. Data on the medical history of the child and
      his/her environment were collected using self-administered questionnaires.
      Analyses were conducted using nonconditional logistic regression. A slight
      negative association with early infections was observed (OR=0.8; 95% CI (0.6
      1.0)). The association was stronger for early gastrointestinal infections. Early
      day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI
      (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months
      and between 3 and 6 months, respectively). No association with breast-feeding was
      observed, irrespective of its duration. A birth order of 4 or more was associated
      with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A
      history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI
      (0.3-0.90). Although the results regarding birth order and breast-feeding do not
      fit with Greaves' hypothesis, the study supports the hypothesis that early common
      infections may play a protective role in the aetiology of childhood leukaemia,
      although this effect was not more marked for common ALL.

PMID- 14710222
TI  - A case-control study of endogenous hormones and cervical cancer.
AB  - Both parity and oral contraceptive use are associated with elevated circulating
      levels of sex hormones, at least transiently, and with increased risk of cervical
      cancer in human papillomavirus (HPV)-infected women. We directly evaluated
      whether elevations in the physiologic levels of these hormones predispose to the
      development of cervical neoplasia. We identified 67 premenopausal and 43
      postmenopausal women with cervical intraepithelial neoplasia 2, 3, or cervical
      cancer (>/=CIN2) diagnosed during enrollment of a population-based cohort of 10
      077 women. Four controls, two chosen randomly and two chosen from women testing
      positive for cancer-associated HPV, were matched to each case on menopausal
      status, age, days since last menses (pre), or years since menopause (post). Sex
      hormone-binding globulin, oestradiol, oestrone, oestrone-sulphate,
      dehydroepiandrosterone sulphate, and progesterone were measured in enrollment
      plasma. There was no consistent association between the sex hormones and risk of
      >/=CIN2. Excluding cases with invasive disease had a minimal impact on results.
      Though this case-control study was based on a well-defined population, it was
      limited by reliance on a single measure of hormone levels taken at the time of
      diagnosis. Nonetheless, our results do not support the hypothesis that plasma
      levels of sex hormones have an important bearing on the risk of cervical
      neoplasia in HPV-infected women.

PMID- 14710223
TI  - Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long
      term results of a prospective study.
AB  - We assessed the association of sex hormone levels with breast cancer risk in a
      case-control study nested within the cohort of 7054 New York University (NYU)
      Women's Health Study participants who were postmenopausal at entry. The study
      includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and
      563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for
      breast cancer for the highest quintile of each hormone and sex-hormone binding
      globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21),
      P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone;
      2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33),
      P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for
      dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for
      SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years
      prior to diagnosis showed results in the same direction as overall analyses,
      although the tests for trend did not reach statistical significance for DHEAS and
      SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95
      cases and their matched controls who had given a second blood donation within 5
      years of diagnosis, were of small magnitude and overall not different in cases
      and controls. The association of androgens with risk did not persist after
      adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95%
      CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the
      oestrogen most strongly associated with risk in our study. Our results support
      the hypothesis that the associations of circulating oestrogens with breast cancer
      risk are more likely due to an effect of circulating hormones on the development
      of cancer than to elevations induced by the tumour. They also suggest that the
      contribution of androgens to risk is largely through their role as substrates for
      oestrogen production.

PMID- 14710224
TI  - Heterogeneity of breast cancer risk within the South Asian female population in
      England: a population-based case-control study of first-generation migrants.
AB  - South Asian women in England have a lower breast cancer risk than their English
      native counterparts, but less is known about variations in risk between distinct
      South Asian ethnic subgroups. We used the data from a population-based case
      control study of first-generation South Asian migrants to assess risks by ethnic
      subgroup. In all, 240 breast cancer cases, identified through cancer registries,
      were individually matched on age and general practitioner to two controls.
      Information on the region of origin, religious and linguistic background, and on
      breast cancer risk factors was obtained from participants. Breast cancer odds
      varied significantly between the ethnic subgroups (P=0.008), with risk increasing
      in the following order: Bangladeshi Muslims (odds ratio (OR) 0.33, 95% confidence
      interval (CI): 0.10, 1.06), Punjabi Hindu (OR 0.59, 95% CI: 0.33, 1.27), Gujarati
      Hindu (1=reference group), Punjabi Sikh (OR 1.23, 95% CI: 0.72, 2.11) and
      Pakistani/Indian Muslims (OR 1.76, 95% CI: 1.10, 2.81). The statistically
      significant raised risk in Pakistani/Indian Muslims increased with adjustment for
      socioeconomic and reproductive risk factors (OR 2.12, 95% CI: 1.25, 3.58), but
      was attenuated, and no longer significant, with further adjustment for waist
      circumference and intake of nonstarch polysaccharides and fat (OR 1.49, 95% CI:
      0.85, 2.63). These findings reveal differences in breast cancer risk between
      South Asian ethnic subgroups, which were not fully explained by reproductive
      differences, but were partly accounted for by diet and body size.

PMID- 14710225
TI  - Kallikrein gene downregulation in breast cancer.
AB  - Recent evidence suggests that many members of the human kallikrein gene family
      are differentially regulated in breast cancer and other endocrine-related
      malignancies. In this study, we utilised the serial analysis of gene expression
      (SAGE) and expressed sequence tag (EST) databases of the Cancer Genome Anatomy
      Project (CGAP) to perform in silico analyses of the expression pattern of the 15
      human kallikrein genes in normal and cancerous breast tissues and cell lines
      using different analytical tools such as Virtual Northern blotting, Digital
      Differential Display and X-profiler. Our results indicate that at least four
      kallikrein genes (KLK5, 6, 8, 10) are downregulated in breast cancer. Probing
      eight normal and 24 breast cancer SAGE libraries with gene-specific tags for each
      of the above kallikreins indicated moderate-to-high expression densities in
      normal breast (27-319 tags per million; tpm, in two to five out of eight
      libraries), compared to no or low expression (0 - 34 tpm in zero to two libraries
      out of 24) in breast cancer. These data were verified by screening the EST
      databases, where all mRNA clones isolated for these genes, except for one in
      each, were from normal breast libraries, with no clones detected from breast
      cancer tissues or cell lines (with the exception of KLK8). X-profiler comparison
      of two pools of normal and breast cancer libraries further verified the presence
      of significant downregulation of expression levels of 4 of the kallikreins genes
      (KLK5, 6, 10, 12). We experimentally verified the downregulation of these four
      kallikreins (KLK5, 6, 8, 10 and 12) by RT - PCR analysis.

PMID- 14710226
TI  - Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial
      cells: comparison of mRNA and protein expression.
AB  - Microarray analysis offers a powerful tool for studying the mechanisms of
      cellular transformation, although the correlation between mRNA and protein
      expression is largely unknown. In this study, a microarray analysis was performed
      to compare transcription in response to overexpression of the ErbB-2 receptor
      tyrosine kinase in a model mammary luminal epithelial cell system, and in
      response to the ErbB-specific growth factor heregulin beta1. We sought to
      validate mRNA changes by monitoring changes at the protein level using a parallel
      proteomics strategy, and report a surprisingly high correlation between
      transcription and translation for the subset of genes studied. We further
      characterised the identified targets and relate differential expression to
      changes in the biological properties of ErbB-2-overexpressing cells. We found
      differential regulation of several key cell cycle modulators, including cyclin
      D2, and downregulation of a large number of interferon-inducible genes,
      consistent with increased proliferation of the ErbB-2-overexpressing cells.
      Furthermore, differential expression of genes involved in extracellular matrix
      modelling and cellular adhesion was linked to altered adhesion of these cells.
      Finally, we provide evidence for enhanced autocrine activation of MAPK signalling
      and the AP-1 transcription complex. Together, we have identified changes that are
      likely to drive proliferation and anchorage-independent growth of ErbB-2-
      overexpressing cancer cells.

PMID- 14710227
TI  - Increased risk of malignant progression in benign proliferating breast lesions
      defined by expression of heat shock protein 27.
AB  - Heat shock protein 27 (hsp-27) is a regulator of oestrogen receptor (ER)
      expression and a modulator of intracellular homeostasis. In this laboratory,
      Shaaban et al demonstrated the importance of ER-alpha, together with Ki67, in
      enhancing the progression of benign breast lesions of defined morphological
      types. To better understand the mechanisms by which ER-alpha promotes breast
      neoplasia, this study was performed to test the hypothesis that the roles of ER
      alpha and hsp-27 may be defined by their quantitative expression in proliferative
      breast lesions of varying histological risk. The expression of hsp-27 was
      identified using a specific monoclonal antibody and analysed to assess the
      proportion of positive epithelial cells using digitised morphometric image
      analysis. The expression of ER-alpha was analysed by immunohistochemistry and
      Western blotting in a variety of benign (HUMA121) and malignant mammary cell
      lines, including ER-alpha(+) (MCF7, ZR-75, T47D) and ER-alpha(-) (MDA-MB 231)
      breast cancer cell lines. The data confirm that, during progression from normal
      through proliferative breast lesions to in situ cancer, there was a significant
      increase in both the proportion and the optical density of the epithelial cells
      expressing hsp-27. The mean levels of expression ranged from 7.4% of the total
      number of epithelial cells in normal lobules to 25.17% of epithelial cells in
      hyperplasias of usual type (HUT) to 61.1% of epithelial cells in ductal carcinoma
      in situ (P<0.001). The study has confirmed the expression of hsp-27 to be closely
      associated with ER-alpha(+) expression, and that its regulated expression occurs
      early along the mammary oncogenic pathway, supporting the initial hypothesis. It
      is our proposal that the differential expression of hsp-27 modulates the
      phenotypic behaviour of morphologically benign epithelial cells and hence may be
      an important determinant in initiating, or promoting, a population of human
      mammary cancers.

PMID- 14710228
TI  - G388R mutation of the FGFR4 gene is not relevant to breast cancer prognosis.
AB  - This study screened large cohorts of node-positive and node-negative breast
      cancer patients to determine whether the G388R mutation of the FGFR4 gene is a
      useful prognostic marker for breast cancer as reported by Bange et al in 2002.
      Node-positive (n=139) and node-negative (n=95) breast cancer cohorts selected for
      mutation screening were followed up for median periods of 89 and 87 months,
      respectively. PCR - RFLP analysis was modified to facilitate molecular screening.
      Curves for disease-free survival were plotted according to the Kaplan - Meier
      method, and a log-rank test was used for comparisons between groups. Three other
      nonparametric linear rank-tests particularly suitable for investigating possible
      relations between G388R mutation and early cancer progression were also used.
      Kaplan - Meier analysis based on any of the four nonparametric linear rank tests
      performed for node-positive and node-negative patients was not indicative of
      disease-free survival time. G388R mutation of the FGFR4 gene is not relevant for
      breast cancer prognosis.

PMID- 14710229
TI  - Analysis of the expression and localisation of a LAP protein, human scribble, in
      the normal and neoplastic epithelium of uterine cervix.
AB  - Recently, a LAP protein, scribble, was identified in Drosophila epithelia as a
      basolateral protein that controls the apical-basolateral polarity. Loss of
      scribble causes disorganisation and overgrowth of the epithelia. Scribble has a
      human homologue, human scribble (hScrib), which is a substrate of ubiquitin
      mediated degradation by human papillomavirus E6 and the E6AP ubiquitin-protein
      ligase. In the present study, we revealed that hScrib localised to the
      basolateral regions of the epithelial cell line MDCK and human uterine cervical
      epithelial tissues by immunofluorescence. Human scribble colocalised rather with
      the adherens junction protein E-cadherin, but not with the tight junction protein
      ZO-1. Histochemical analysis showed a dramatic decrease in the expression of
      hScrib with the progression of disease from normal uterine cervical tissues to
      invasive cervical cancers through the precursor lesions. In contrast, the
      expression of hScrib was retained in the throughout epithelial layer of the HPV
      negative cervical high-grade squamous intraepithelial lesions (H-SIL). Although
      quantitative RT-PCR revealed no significant downregulation of hScrib mRNA
      expression in the H-SIL, it revealed a clear downregulation in the invasive
      cancers. These results suggest the possibility that degradation by HPV E6 is one
      of the causal roles for the progressive decrease of hScrib expression during the
      disease progression from low-grade squamous intraepithelial lesions to H-SIL, and
      a cooperative role of downregulation of hScrib mRNA expression and ubiquitin
      mediated degradation of hScrib by E6 and E6AP led to the complete decrease of
      hScrib expression during the process of carcinogenesis from H-SIL to invasive
      cancer. These data underscore the importance of hScrib in the construction of
      tissue architecture and prevention of cancer development.

PMID- 14710230
TI  - Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma
      patients.
AB  - Previously, we reported that Bcl-2 was frequently expressed in renal cell
      carcinoma (RCC) specimens, but p53 mutation was a rare event. However, it was
      unclear whether Bcl-2 positivity was associated with the clinicopathological
      characteristics and prognosis in RCC. Therefore, we investigated the expression
      of Bcl-2 protein and its roles in 101 RCC specimens. In addition, the
      proliferation index (PI), apoptotic index (AI), caspase-3 and p53 expression were
      examined. The immunohistochemical method was applied for Bcl-2, caspase-3 and p53
      protein expression. To investigate the proliferation activity and apoptosis of
      tumour cells, PI and AI were calculated based on Ki-67 and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL)
      positive cells, respectively. Bcl-2 expression was detected in 72 out of 101
      (71.3%) specimens. Bcl-2 positivity was inversely correlated with PI (P<0.0001)
      and AI (P=0.0074). Furthermore, Bcl-2 positivity was significantly correlated
      with better survival (P=0.0014), and was associated with lower stage (P=0.0301)
      and grade (P=0.0020). In RCC, frequent Bcl-2 expression was correlated with
      favourable character without higher PI and AI. Thus, Bcl-2 expression might be
      applied as a novel predictor of better prognosis in RCC patients.

PMID- 14710231
TI  - p53 and VEGF expression are independent predictors of tumour recurrence and
      survival following curative resection of gastric cancer.
AB  - This study was undertaken to determine the value of tumour microvessel density
      (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as
      prognostic markers in patients with gastric cancer operated on for cure. In all,
      156 patients with curatively resected gastric cancer constituted the basis of
      this blinded retrospective evaluation. Patients were treated with either surgery
      alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53
      expression, and VEGF expression were assayed using immunohistochemical
      techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and
      55 (35%) patients developed tumour recurrence. Positive correlations between MVD
      and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD
      >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with
      shorter disease-free survival, and positive VEGF expression (P=0.01) was also
      associated with shorter overall survival. Multivariate analysis confirmed that,
      in addition to the pathological tumour stage, lymph node ratio, the extent of
      lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were
      independently associated with both disease-free survival (P<0.0005 and 0.02,
      respectively) and overall survival (P<0.02 and 0.01, respectively). Finally,
      patients whose tumours did not show p53 expression had a survival benefit
      compared to those expressing p53 when treated with adjuvant chemotherapy
      (P=0.01). This investigation demonstrates that p53 expression and VEGF expression
      are independent prognostic factors for both disease-free survival and overall
      survival in patients with curatively resected gastric cancer, and that p53 status
      may also influence response to chemotherapy.

PMID- 14710232
TI  - Differential gene-expression profiles associated with gastric adenoma.
AB  - Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The
      purpose of the present study was to identify gene-expression profiles linked to
      the heterogeneous nature of gastric adenoma as compared to adenocarcinoma.
      Suppression subtractive hybridisation analysis was performed to extract relevant
      genes from two cases of low- and high-grade gastric adenomas. The identified
      genes were quantified by RT-PCR in 14 low-grade adenoma, nine high-grade adenoma
      and nine adenocarcinoma samples, followed by hierarchical clustering analysis to
      separate tumours into groups according to their gene-expression profiles. Nine
      genes previously implicated in carcinogenesis in a variety of organs, including
      three genes related to gastric adenocarcinoma, were identified. The
      overexpression of these genes in gastric adenoma has not been reported
      previously. The clustering analysis of these nine genes across 32 cases
      identified three groups, one of which consisted primarily of adenocarcinomas,
      whereas the other two groups consisted of adenomas. One group of adenomas,
      characterised by larger tumour size, exhibited gene-expression profiles of an
      intestinal cell lineage implicated in the pathogenesis of an intestinal-type
      gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas
      with smaller tumour size exhibited a unique expression profile. In conclusion,
      clustering analysis of expression profiles using a limited number of genes may
      serve as molecular markers for gastric adenoma with different biological
      properties. Although the prognostic values of these gene-expression profiles need
      to be evaluated in further follow-up study of adenoma cases, these findings add
      new insights to (a) our understanding of the pathogenesis of gastric tumours, (b)
      the development of specific tumour markers for clinical practice, and (c) the
      design of novel therapeutic targets.

PMID- 14710233
TI  - Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas
      of patients with familial adenomatous polyposis and in human colorectal cancer
      cell lines.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive potential
      against colorectal carcinomas (CRCs). Inhibition of cyclooxygenase (COX)-2
      underlies part of this effect, although COX-2-independent mechanisms may also
      exist. Nonsteroidal anti-inflammatory drugs appear to inhibit the initial stages
      of the adenoma-carcinoma sequence, suggesting a link to the APC/beta-catenin/TCF
      pathway (Wnt-signalling pathway). Therefore, the effect of the NSAID sulindac on
      nuclear (nonphosphorylated) beta-catenin and beta-catenin/TCF-mediated
      transcription was investigated. Nuclear beta-catenin expression was assessed in
      pretreatment colorectal adenomas and in adenomas after treatment with sulindac
      from five patients with familial adenomatous polyposis (FAP). Also, the effect of
      sulindac sulphide on beta-catenin/TCF-mediated transcription was studied.
      Adenomas of FAP patients collected after treatment with sulindac for up to 6
      months showed less nuclear beta-catenin expression compared to pretreatment
      adenomas of the same patients. Sulindac sulphide abrogated beta-catenin/TCF
      mediated transcription in the CRC cell lines DLD1 and SW480, and decreased the
      levels of nonphosphorylated beta-catenin. As a result, the protein levels of the
      positively regulated TCF targets Met and cyclin D1 were downregulated after
      sulindac treatment. This study provides in vivo and in vitro evidence that
      nuclear beta-catenin localisation and beta-catenin/TCF-regulated transcription of
      target genes can be inhibited by sulindac. The inhibition of Wnt-signalling
      provides an explanation for the COX-2-independent mechanism of chemoprevention by
      NSAIDs.

PMID- 14710234
TI  - Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2
      positive breast cancer cells.
AB  - Due to its pivotal role in the growth factor-mediated tumour cell migration, the
      adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to
      block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby
      minimising metastasis formation. Here, we present an approach to block PLC-gamma1
      activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1
      SH2 domains, which were fused to the TAT-transduction domain to ensure a high
      protein transduction efficiency. Two proteins were generated containing one PLC
      gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT
      treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a
      reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%,
      concomitant with a complete abrogation of the EGF-driven calcium influx. In
      addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated
      migration of about 75% combined with a markedly decreased time locomotion of
      single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by
      about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast
      cancer cells, we conclude from our results that the protein-based PLC-gamma1
      inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to
      minimise metastasis formation because of the blockade of cell migration and
      proliferation.

PMID- 14710235
TI  - Additive antitumour effect of the epidermal growth factor receptor tyrosine
      kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant
      (Faslodex, ICI 182,780) in breast cancer cells.
AB  - A high expression level of epidermal growth factor receptor (EGFR)/HER1 has been
      suggested to lead to a shorter survival time and resistance to endocrine therapy
      in patients with breast cancer. To test the hypothesis that inhibition of the
      EGFR signalling pathway affects the antitumour effect of endocrine therapy, an
      EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, and an oestrogen receptor
      (ER) antagonist, fulvestrant, were administered to human breast cancer cells. A
      total of five human breast cancer cell lines were used. The effects of single or
      combined treatments with gefitinib and/or fulvestrant on cell growth, cell cycle
      progression and apoptosis were analysed. Changes in the expression levels of
      cyclin-dependent kinase inhibitors, p21 and p27, an antiapoptotic factor, Bcl-2,
      and a proapoptotic factor, Bax, were also investigated. All cell lines tested
      were sensitive to gefitinib (50% growth inhibitory concentration, 10-28.5
      microM). Breast cancer cell lines with a high expression level of HER1 or HER2
      were more sensitive to gefitinib than the others. Gefitinib induced a significant
      G1-S blockade in ER-positive KPL-3C cells. Gefitinib induced significant
      apoptosis in HER1-overexpressing MDA-MB-231 cells. Gefitinib additively increased
      the antitumour effect of fulvestrant in all three ER-positive cell lines in a
      medium supplemented with 17beta-oestradiol. The combined treatment promoted cell
      cycle retardation in KPL-3C cells, which is associated with an upregulation of
      p21 by fulvestrant and gefitinib, respectively. Apoptosis was associated with
      downregulation of Bcl-2 by gefitinib in MDA-MB-231 cells. These results suggest
      an additive interaction between the EGFR-TKI gefitinib and the antioestrogen
      fulvestrant in ER-positive breast cancer cells.

PMID- 14710237
TI  - S100A4 regulates cell motility and invasion in an in vitro model for breast
      cancer metastasis.
AB  - Elevated levels of the calcium-binding protein S100A4 are associated with poor
      patient survival in breast cancer patients and induce metastasis in rodent
      models. To investigate the effects of S100A4 on different components of the
      metastatic process, epithelial cells lines have been isolated from nonmalignant
      tumours in neu transgenic mice and from malignant tumours in neu/S100A4 double
      transgenic mice. Additional cell lines expressing both Neu and S100A4 have also
      been derived by transfection of rat S100A4 cDNA into tumour cell lines cloned
      from neu single transgenic mice. Using these cells in transfilter migration
      assays, it has been shown that increases in either motility or invasive
      properties correlate with each other and with the level of S100A4 protein.
      Injection of three of the cell lines separately into the mammary fat pads of nude
      mice showed that elevated levels of S100A4 correlated with the degree of
      metastasis to the lungs. In contrast, changes in cell proliferation and cell
      substrate adhesion did not correlate with S100A4 levels. Neither motility nor
      invasiveness correlated with proteolytic degradation of gelatin as measured by
      zymography. Thus, the results suggest that the main effect of increases in S100A4
      levels in metastasis is to generate increased cell motility and invasion and that
      this latter change is not dependent upon an increased ability to degrade the
      intercellular matrix.

PMID- 14710236
TI  - Bombesin antagonists inhibit proangiogenic factors in human experimental breast
      cancers.
AB  - The overexpression of angiogenic factors such as vascular endothelial growth
      factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors
      (IGFs) plays a role in the migration and proliferation of endothelial cells in
      many cancers. Consequently, we investigated the effects of bombesin/gastrin
      releasing peptide (GRP) antagonists on the expression of these angiogenic
      factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as
      the vascular density in MDA-MB-435 human oestrogen-independent breast cancers.
      Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated
      with bombesin/GRP antagonists for 6 weeks. Daily administration of 20 microg of
      RC-3095 or 10 microg of RC-3940-II significantly decreased the weight of MDA-MB
      435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was
      associated with a substantial reduction in the expression of mRNA and protein
      levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the
      tumours. Both bombesin/GRP antagonists significantly decreased the vessel density
      of the tumours by about 37%, as shown by immunohistochemical detection of vessels
      on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33
      46% reduction in MMP-9 activity after the treatment with either antagonist. In
      vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and
      the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study
      demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC
      3940-II, and underscores their possible therapeutic application for treatment of
      breast cancers.

PMID- 14710238
TI  - Encapsulation into sterically stabilised liposomes enhances the immunogenicity of
      melanoma-associated Melan-A/MART-1 epitopes.
AB  - Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic
      reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are
      currently used in clinical applications despite an acknowledged poor
      immunogenicity. Encapsulation into liposomes has been suggested to improve the
      immunogenicity of discrete antigen formulations. We comparatively evaluated the
      capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or
      following inclusion into sterically stabilised liposomes (SSL) to be recognised
      by specific CTL, to stimulate their proliferation and to induce them in healthy
      donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived
      tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma
      cells served as targets of specific CTL in 51Cr release assays upon pulsing by
      untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27
      35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to
      stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the
      presence of immature dendritic cells (iDC), as antigen-presenting cells (APC).
      Induction of specific CTL upon stimulation with soluble or SSL-encapsulated
      peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and
      monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with
      SSL M27-35 resulted in a five-fold more effective killing by specific CTL as
      compared with equal amounts of S M27-35. Encapsulation into SSL also provided a
      partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages
      regarding M26-35 were detectable in these assays. However, at low epitope
      concentrations (</=100 ng ml(-1)), SSL M26-35 was significantly more effective in
      inducing CTL proliferation than S M26-35, in the presence of iDC, as APC.
      Preincubation with iDC for 6 h virtually abolished the capacity of S M26-35 to
      stimulate specific CTL proliferation, but only partially affected that of SSL M26
      35. Most importantly, SSL M26-35 was able to enhance the induction of specific
      CTL in healthy donors PBMC and in melanoma-derived TIL as compared to S M26-35.
      Taken together, our data indicate that encapsulation of TAA epitopes into SSL
      results in effective immunogenic formulations suitable for clinical use in active
      specific tumour immunotherapy.

PMID- 14710240
TI  - Improved safety and effectiveness of imaging predicted for MR mammography.

PMID- 14710239
TI  - Highly selective toxic and proapoptotic effects of two dimeric ribonucleases on
      thyroid cancer cells compared to the effects of doxorubicin.
AB  - The lack of selectivity of conventional antitumour drugs against cancer cells is
      responsible for their high toxicity. The development of new tumour-specific drugs
      is therefore highly needed. We tested the cytotoxic effects and the nature of
      cell death induced by a naturally dimeric bovine RNase and a newly engineered
      dimeric human RNase upon three genetically well-defined normal and malignant
      thyroid cell systems. RNases effects were compared with those of doxorubicin, a
      conventional antineoplastic drug. Our results show significant and selective
      proapoptotic effects exerted on tumour cells by both RNases, the strength of
      their cytotoxic and apoptotic activity being directly related to the degree of
      cell malignancy. No toxic effects were observed upon normal cells. Doxorubicin
      showed, instead, cytotoxic and apoptotic effects also against normal cells. The
      in vitro results were corroborated by the antitumour action of both dimeric
      RNases towards a malignant human thyroid tumour grown in nude mice. These results
      indicate a selective action of dimeric RNases against cancer cells and suggest
      the potential application of these molecules or their derivatives to the
      treatment of aggressive subtypes of thyroid cancer.

PMID- 14710244
TI  - [Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide, alone or
      in combination, on the rat hearts in vitro].
AB  - OBJECTIVE: To study the effects of adrenomedullin (ADM) and proadrenomedullin N
      terminal 20 peptide (PAMP) alone or in combinations on the isolated rat hearts as
      well as the possible signaling pathways involved in their actions. METHODS: In
      isolated rat hearts the left ventricular pressure (LVP), LVP+/-dp/dtmax, coronary
      fluid (CF) and heart rate(HR) of the hearts infused at different concentrations
      of ADM and/or PAMP were determined by a 4-cannal physiological recorder, then the
      cAMP contents were assayed in myocardium. RESULTS: After being infused with ADM
      from 10(-11) to 10(-8) mol x L(-1) or PAMP from 10(-11) to 10(-8)mol x L(-1), the
      LVP and LVP+/-dp/dtmax of the isolated hearts decreased gradually in a
      concentration-dependent manner, and at the same concentration, the effects of
      PAMP were more potent than those of the ADM. When ADM and PAMP were co
      administrated with both concentrations as low as from 10(-11) to 10(-10) mol x L(
      1), the cardiac parameters were decreased more than either ADM or PAMP
      administrated alone. However, the inhibitory effects of ADM and PAMP were
      attenuated when they were in combination at higher concentrations as from 10(-9)
      to 10(-8) mol x L(-1). When the rat hearts were infused with ADM PAMP and ADM
      plus PAMP, the CF were always higher than those of the controls and decreased
      when co-administrated with L-NAME, an inhibitor of NOS, but the decreased degree
      of LVP and LVP+/-dp/dtmax were attenuated by L-NAME. The cAMP contents in the
      left cardiac ventricle were increased significantly by ADM infusions but not
      changed obviously by PAMP, and were of no statistical difference in rat hearts
      with ADM administrated alone from those combinated with ADM and PAMP. CONCLUSION:
      These results showed that ADM and PAMP infused alone or in combinations inhibited
      the function of rat hearts in vitro, which might be partly involved with the
      NOS/NO pathway.

PMID- 14710245
TI  - [Effects of high pulmonary blood flow on pulmonary vascular structure and the
      gene expression of cystathionine-gamma-lyase].
AB  - OBJECTIVE: To examine the alteration of pathologic structure and endogenous
      hydrogen sulfide pathway in rats with pulmonary hypertension induced by high
      pulmonary blood flow. METHODS: Sixteen SD rats were randomly divided into
      shunting group and control group. An 11-week aortocaval shunting was produced in
      rats of shunting group, and pulmonary artery mean pressure (mPAP) was evaluated
      using right cardiac catheterization. The ratios of right ventricular mass to body
      weight (RV/BW) and right ventricular mass to left ventricular plus septal mass
      [RV/(LV+S)] were also detected. Pulmonary vascular micro- and ultra- structures
      were examined. Meanwhile the concentration of plasma hydrogen sulfide (H(2)S) was
      measured by spectrophotography. The gene expression of cystathionine-gamma-lyase
      (CSE)was detected by in situ hybridization, and the activity of CSE in lung
      tissues was measured by H(2)S production according to chemical analysis. RESULTS 
      After 11 weeks of aortocaval shunting, pulmonary artery mean pressure was
      significantly increased. Muscularization of small pulmonary vessels and relative
      medial thickness of pulmonary arteries were obviously increased in shunting rats
      compared with controls. Ultrastructure of intrapulmonary arteries changed
      obviously in shunting rats. Meanwhile, plasma H(2)S concentration was decreased
      and the activity of CSE (according to H(2)S production) in lung tissues decreased
      in shunting rats. CSEmRNA expression by pulmonary arteries was significantly
      suppressed. CONCLUSION: Pulmonary vascular structural remodeling is the important
      pathologic basis for pulmonary hypertension induced by high pulmonary blood flow.
      The down-regulation of endogenous H(2)S pathway might play an important role in
      the development of high pulmonary blood flow  induced pulmonary hypertension.

PMID- 14710246
TI  - [Effects of hypoxia on heme oxygenase/carbon monoxide and type I collagen in
      pulmonary artery smooth muscle cells of rats].
AB  - OBJECTIVE: To explore changes of expression of heme oxygenase (HO) and production
      of endogenous carbon monoxide in hypoxic pulmonary artery smooth muscle cells
      (PASMCs) of rats and study their effects on type I collagen under hypoxia.
      METHODS: PASMCs of rats were cultured in vitro and incubated under hypoxic
      condition for 24 hours. The relative content of CO released into medium by PASMCs
      was detected using spectrophotometry. Western blot was applied to assay the
      expressions of HO-1 and transforming growth factor-beta(3) (TGF-beta(3)). The
      expressions of HO-1, TGF-beta(3) and type I collagen were detected by
      immunohistochemical assay. The expressions of procollagen type I were detected by
      in situ hybridization. RESULTS: Hypoxia induced the expression of TGF-beta(3),
      type I collagen and mRNA in rat PASMCs, elevated the expression of HO-1 and CO
      content compared to controls by 67.45% (P<0.01) and 35.41% (P<0.05),
      respectively. In the hypoxic PASMCs treated with protoporphyrin-IX (ZnPP)(10
      micromol x L(-1)), an inhibitor of HO, the expression of HO-1 and the CO content
      were 23.9%(P<0.05), 7.88% (P<0.01) lower than those of hypoxic PASMCs,
      respectively. ZnPP promoted the expression of TGF-beta(3) (393%,P<0.01), type I
      collagen protein and mRNA in hypoxic PASMCs. Hemin (20 micromol x L(-1)), an
      inducer of HO, caused an increase in the expression of HO-1 and CO content in
      hypoxic rat PASMCs by 105% (P<0.05), 8.83% (P<0.01) compared to hypoxic PASMCs,
      respectively. Hemin inhibited the expression of TGF-beta(3) by 68.12% (P<0.01),
      and type I collagen protein and mRNA in hypoxic PASMCs. CONCLUSION: HO/CO system
      is up-regulated by hypoxia and endogenous CO may play an important role in
      decreasing collagen synthesis and inhibiting the expression of TGF-beta(3) in
      hypoxic rat PASMCs.

PMID- 14710247
TI  - [Ultrastructural and immunoelectron microscopic study on light chain deposition
      diseases and primary amyloidosis of the kidney].
AB  - OBJECTIVE: To investigate the role of electron microscopy (EM) and immunoelectron
      microscopy (IEM) in the diagnosis of light chain deposition diseases (LCDD) and
      primary amyloidosis (AL) of the kidney. METHODS   Renal biopsy specimens
      collected in our hospital from Jan. 1994 to Feb. 2002 were studied by EM, and
      ultrastructural immunogold labeling for light chains (kappa, Lambda) were made on
      the cases suggested of LCDD and early stage AL in the preliminary diagnosis.
      RESULTS: Six cases were diagnosed as LCDD, and punctate, granular, electron-dense
      material was identified in the outside of tubular basement membrane (TBM), inner
      layer of glomerular basement membrane (GBM) and vascular walls by EM. Two of
      which showed interrupted segmental localization of granular material in
      subendothelial areas of GBM. The granular material was labeled by monotypical
      light chains (4 cases of kappa chain, 2 cases of Lambda chain). Thirty-six cases
      were diagnosed as AL. EM revealed fibrillary material distributed in glomerular
      mesangium, GBM and vascular walls; 15 of them showed segmental distribution of
      fibrils in mesangium and/or GBM, and were further studied by IEM labeling for
      light chains. The fibrillary material was labeled by monotypical light chains (4
      cases of kappa chain, 11 cases of Lambda chain). CONCLUSION   The diagnosis of
      renal LCDD and early stage of AL depended on EM, IEM is a unique diagnostic tool
      in early stage of LCDD and AL.

PMID- 14710248
TI  - [Use of biopsy results to predict capsular perforation and seminal vesicle
      invasion in prostate cancer].
AB  - OBJECTIVE: To determine the ability of clinical tests to predict extraprostatic
      cxtension and seminal vesicle invasion. METHODS: Clinical T stage, TPSA total
      prostate specific antigen and pathologic features in systematic biopsy specimens
      were correlated with pathologic stage in 40 consecutive patients with clinically
      localized prostate cancer detected by systematic needle biopsies and treated with
      radical prostatectomy. RESULTS: Extraprostatic extension was observed in 20
      patients (50%) and seminal vesicle invasion was noted in 11(28%). Preoperative
      variables predictors of extraprostatic extension and seminal vesicle invasion on
      univariate analysis were TPSA, Gleason score, the total length of cancer, the
      number of positive cores, the percentage of positive cores, the maximum length of
      cancer in any one core in the biopsy specimen and the percentage of cancer in the
      biopsy set P<0.05 . In multivariate analysis, TPSA, Gleason score, the total
      length of cancer and the percentage of positive cores in the biopsy specimens
      were the only significant predictors of extraprostatic extension and seminal
      vesicle invasion P<0.01 . A model was constructed to predict advanced stage: the
      TPSA >or=11 microg x L(-1) and Gleason score/5 and percentage of positive cores
      in the biopsy specimen >or=27% or the total length of cancer>or=7.3 mm P<0.001 .
      CONCLUSION: The combination of TPSA, the total length of cancer, Gleason score
      and percentage of positive cores in the biopsy specimens provides the best
      prediction of capsular perforation and seminal vesicle invasion. Models based on
      this combination of factors may be clinically useful to stratify patients for
      nonoperative treatment.

PMID- 14710250
TI  - [Heritability of insulin sensitivity in twins].
AB  - OBJECTIVE: To explore the contribution of genetic and environmental effects to
      insulin sensitivity. METHODS: The insulin sensitivity of 249 pairs of twins was
      estimated by use of logarithm transformed homeostasis model assessment (HOMA), of
      whom 169 pairs were monozygous and 80 pairs dizygous. To formulate a univariate
      genetic model for the variation of insulin sensitivity, the relative influences
      of gene and environment on the insulin sensitivity were divided into four
      contributing components as A (additive effects of alleles),D (dominance effects) 
      C (common environmental effects) and E (specific environmental effects).
      Heritability of insulin sensitivity was estimated by maximum  likelihood method,
      which included the influences of age and sex on model. RESULTS: The influence of
      age on insulin sensitivity was not significant  chi(2)=1.851  P=0.604  . The AE
      model fitted the data best. The heritability of insulin sensitivity was 0.35 in
      males and 0.46 in females, respectively. CONCLUSION: 35% of the variance in
      insulin sensitivity was due to additive effects in males and 46% due to additive
      effects in females in this twin study.

PMID- 14710249
TI  - [Expressions of MAD2 and p55CDC in prostate cancer and their correlations with
      the prostate cancer grading].
AB  - OBJECTIVE: To investigate if downregulation of two mitotic checkpoint proteins,
      MAD2 and p55CDC, is a frequent event in human prostate cancer and whether
      decreased expression of these two proteins are associated with progression of
      prostate cancer. METHODS: Using immunohistochemistry technique, the expressions
      of MAD2 and p55CDC proteins are examined in 46 benign prostate hyperplasia (BPH)
      and 65 prostate cancer tissues. Differential expressions were compared first
      between BPH and prostate cancer specimens, and then among prostate cancer samples
      with different Gleason grades. RESULTS: We found that down-regulation of MAD2 and
      p55CDC expressions was significant in prostate cancer (96% and 83%, respectively)
      compared to BPH (19.5% and 4.3%, respectively) (P<0.001). In addition, decreased
      expression levels of these two proteins were associated with increased Gleason
      grade. CONCLUSION: Our results indicate that loss of MAD2 and p55CDC protein
      expression is a frequent event in prostate carcinoma and the decreased
      expressions of these two proteins are associated with increased Gleason grade.
      Our results provide first in vivo evidence to support the hypothesis that down
      regulation of certain mitotic checkpoint proteins plays an important part in
      human tumourigenesis.

PMID- 14710251
TI  - [Risk factors of cytomegalovirus infection and antiviral efficacy in recipients
      of hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To analyze the incidence, risk factors and antiviral effect of
      cytomegalovirus infection after hematopoietic stem cell transplantation (HSCT).
      METHODS: Two hundred and two patients who underwent HSCT in our institution from
      Jan, 1998 to Dec, 2000 were analyzed in a retrospective way. Conditioning
      regimens consisted of total body irradiation (TBI) or busulfan plus
      cyclophosphomide. Allo-HSCT patients received cyclosporn A and short-term
      methotrexate as graft-versus host disease (GVHD) prophylaxis. As prophylaxis of
      CMV infection, 10 mg x (kg(-1) x d(-1)) ganciclovir were used per day for eight
      days before HSCT. Cytomegalovirus was detected after HSCT once a week using
      polymerase chain reaction (PCR) method. If CMV was positive or patients had signs
      of CMV disease, ganciclovir or/and foscarnet was used for the treatment. RESULTS:
      The incidence of CMV infection was 35.6% (72/202). Among these active infections,
      interstitial pneumonia accounted for 44.4%, viraemia 33.3% and CMV enteritis
      13.9%. The peak interval of infection was from 60 to 90 days after HSCT.
      Effective rate of anti-CMV treatment was about 60%. Allo-HSCT, acute and chronic
      GVHD were important risk factors for CMV infection. Age, sex, disease status
      before HSCT, pre-conditioning regimen were not significantly associated with the
      occurrence of CMV infection. CONCLUSION: CMV infection is one of the important
      complications of allo-HSCT.Effective prevention and treatment may improve the
      survival rate for these patients.

PMID- 14710252
TI  - [Effect of glucose-free treatment on the neural precursor cells in vitro].
AB  - OBJECTIVE: To investigate the survival, division, and differentiation of neural
      precursor cells (NPCs) following glucose-free treatment in vitro. METHODS:
      Cultured neonatal rat hippocampal NPCs were exposed to glucose-free media for 6
      hours, and then were returned to regular media containing normal level glucose.
      At different time points after glucose-free treatment, trypan blue staining was
      used to determine cell viability, MTT assay to measure cell metabolic rate, 5'
      bromo-deoxyuridine (BrdU) incorporation to determine the NPCs division, and
      immunocellulochemistry and western blot analysis to study the NPCs
      differentiation. RESULTS: (1) At different time points (0, 1, 7 d) after glucose
      free treatment, NPCs viability decreased compared with NPCs control. On 0 and 1 d
      after glucose-free treatment, NPCs viability was higher than neurons viability.
      (2) On 0 and 1 d after glucose-free treatment, NPCs metabolic rates decreased
      significantly compared with NPCs control. On 0, 1, and 7 d after glucose-free
      treatment, NPCs metabolic rates were higher than that in neurons. (3) After
      glucose-free treatment, BrdU incorporation of NPCs was similar to NPCs control
      (P>0.05). (4) After glucose-free treatment, NPCs differentiation didn't change
      significantly (P>0.05). CONCLUSION: These findings demonstrated that glucose-free
      treatment impaired NPC's viability, but didn't affect the division and
      differentiation of NPCs.

PMID- 14710253
TI  - [Integrin alpha6 beta4 and experimental allergic neuritis].
AB  - OBJECTIVE: To explore the relationship between integrins alpha6,beta4 and the
      process of the injury and repair of the myelin, their expressions in experimental
      allergic neuritis were analyzed. METHODS: Experimental allergic neuritis (EAN)
      models were induced in Lewis rats. The expressions of integrins alpha6 and beta 4
      and their receptor laminin, both in the acute phase and recovery phase of EANs,
      were analyzed by in situ hybridization and immunohistochemistry. RESULTS: The
      expression of beta4 decreased in the acute phase P<0.05 and showed no significant
      changes in the recovery phase(P=0.6840). There were no significant changes of the
      expression of alpha6 and laminin both in the acute phase and recovery phase of
      EANs by immunohistochemistry (alpha6 P=0.0751;laminin P=0.2047). The similar
      results were obtained by in situ hybridization (beta4 in acute phase P<0.05;beta4
      in recovery phase P=0.823;alpha6 P= 0.81). CONCLUSION: The expressions of
      integrins of Schwann cells were affected by inflammation injury, and their
      patterns of expression were similar to those of integrins alpha6, beta1 and beta4
      during embryogenesis. It is inferred that integrin beta4 and the reformation of
      myelin have a more imitate relationship. The expression changes of alpha6 and
      beta4 correlate with the injury and repair of myelin during EAN.

PMID- 14710254
TI  - [Coronary artery bypass grafting in patients following percutaneous coronary
      interventions].
AB  - OBJECTIVE: To investigate and analyze the clinical outcomes of coronary artery
      bypass grafting (CABG) in patients with history of previous percutaneous coronary
      interventions (PCI). METHODS: We studied 76 patients with a history of PCI who
      underwent CABG surgery in our institute from August of 1999 to April of 2002,
      which was 14.0 percent of concurrent CABG. There were 39 cases with PTCA alone
      and 37 combined with stent implantation, of whom 5 had undergone re-do PCI
      therapy. Then 46 patients encountered re-stenosis and 6 developed new lesion in
      native coronary arteries. There were 4 cases with unsuccessful PCI, 11 cases with
      residual lesion in important vessels and 9 cases with acute complications during
      PCI. There was a higher incidence of myocardial infarction in group PCI than that
      in group Non-PCI, and a lower incidence of triple vessel disease (P<0.01).
      RESULTS: Group PCI had more emergent surgeries (27.6% vs 13.3%) and fewer OPCAB
      procedures (91.3% vs 97.2%) than group Non-PCI (P<0.01). The mean number of
      distal anastomosis in group PCI was smaller than that in group Non-PCI (P<0.01).
      There were 6 people who died in group PCI, of whom 3 died of heart pump failure,1
      of ventricular fibrillation, 1 of neurological complication, and 1 of renal
      failure. The mortality of group PCI was higher than group Non-PCI (7.9% vs 1.9%,
      P<0.01). In group PCI, there were 4 with peri-operative myocardial infarction, 1
      with late death and 1 with recurrent angina pectoris. CONCLUSION: CABG is usually
      the most effective and necessary way to treat PCI failure, unsatisfactory
      revascularization and its acute complications. It is most important to promptly
      and appropriately deal with acute complications of PCI in reducing the mortality.

PMID- 14710255
TI  - [Effects of hydroxyl radicals  low density lipoprotein and cholesterol on the
      calcium  responding behavior of vascular endothelial cells].
AB  - OBJECTIVE: To investigate the effects of hydroxyl radicals, low density
      lipoprotein and cholesterol on the response of vascular endothelial cells to the
      change in extracellular calcium ion concentration. METHODS: After treatment with
      the above mentioned atherogenic factors respectively, the cells were loaded with
      Fluo-3 and then the response of the cells to the increase in extracellular
      [Ca(2+)] was observed under a confocal laser scanning microscope. RESULTS: Normal
      vascular endothelial cells were sensitive to the increase in extracellular
      [Ca(2+)]. The free calcium ions in cytosol increased pulsively until a maximum
      was reached, and then was reduced to the initial level rapidly. Treatment with
      hydroxyl radicals produced by Fe(2+)-EDTA made the cells rather slow to the
      change in extracellular [Ca(2+)]. A morphological examination showed that some
      damage to the cells was caused. After cultivation with low density lipoprotein
      (0.10 g x L(-1)), the cells lost most of their capability to modulate
      intracellular calcium ion and thus the calcium level remained high at the end of
      the experiment. If a hydroxyl radical treatment preceded the incubation with low
      density lipoprotein, a more serious damage was observed. Some of the cells were
      caused to death while the extracellular [Ca(2+)] increased. Upon exposing to a
      higher level of extracellular calcium ion, the cytosol [Ca(2+)] did not increase;
      contrarily, it decreased gradually. The hydroxyl radical oxidation followed by
      cholesterol treatment made the cells respond disorderly to the increase in
      extracellular [Ca(2+)], indicating that rather serious damage had been caused to
      the cells. CONCLUSION: These findings indicate that hydroxyl radicals, low
      density lipoprotein and cholesterol interfere with the response of vascular
      endothelial cells to extracellular calcium ions. This may be one of the ways
      these factors contribute to the initiation and development of atherosclerosis.

PMID- 14710256
TI  - Electrochromatographic properties of synthetic poly(styrene-divinylbenzene)
      encapsulated packing material and sulphonic cation-exchange phase based on the
      former.
AB  - OBJECTIVE: To develop new kinds of stationary phases suitable for applications in
      capillary electrochromatography (CEC), as well as in LC, which can be tailored to
      realize selective separations of solutes difficult to separate with conventional
      stationary phases. METHODS: Purchased spherical silica particles (5 microm) were
      refluxed in anhydrous toluene with vinyl-triethoxysilane for 18 h, to modify the
      surface with vinylsilyl groups. The silylated silica particles were subsequently
      stirred in an n-henanol-acetonitril mixture (1:4, volume fraction) for 18 h.
      Styrene and divinylbenzene in the mixture co-polymerized to form a crosslinked
      encapsulation layer on the silica surface, and bonded on the surface vinyl groups
      at the same time, both reactions were initiated by azo-iso-butyronitrile. The
      poly(Styrene-divinylbenzene) encapsulated silica(PS-DES) produced can be used as
      a non-conventional stationary phase for CEC itself. By sulphonation of the PS-DES
      phase with chlorosulphonic acid, strong cation-exchange stationary phase of
      sulphonic type was obtained. RESULTS: The manufactured PS-DES as well as the
      sulphonated phases were respectively packed into capillaries,and the columns thus
      prepared were tested for their chromatographic characteristics. It was found that
      the PS-DES phase showed reversed-phase characteristics. Due to the phenyl groups
      in the encapsulated polymer, it introduced pi-pi electronic interaction between
      the solutes molecules and stationary phase during the chromatographic separation
      process, therefore it showed unique selectivity on separating aromatic compounds,
      also polar- as well as some alkaline drugs was analyzed on the column packed with
      the phase. It was demonstrated that the sulphonated phase could be used to
      prepare columns for the separation of alkaline drugs, symmetric peaks were
      obtained for them and base-line separation was realized. CONCLUSION: It is
      possible that these stationary phases prepared can be used for solving the
      analytical problems in which non-conventional selectivity are needed ( the
      analyses of alkaline drugs are examples) In some cases, the analysts can realize
      the anticipated separation results based on the different separation mechanism
      from that of the conventional stationary phases.

PMID- 14710257
TI  - [La accumulation and microstructure change of leg bones of rats fed with
      La(NO(3))(3) in low dosage for a long term].
AB  - OBJECTIVE: To study La accumulation and microstructure change of leg bones of
      rats fed with La(NO(3))(3) in low dosage for a long term. METHODS: After the rats
      were fed by La(NO(3))(3) in dosage of 2 mg x (kg(-1) x d(-1)) for 6 months, the
      contents of La and Ca,P in the leg bones were determined by ICP MS and
      spectrophotometry; the microstructure changes of the leg bones were investigated
      by electron microscopy and X-ray powder diffraction. RESULTS: In the leg bones of
      tested rats, the contents of La and P increased greatly, and those of Ca did not
      change obviously, so that Ca/P ratio values decreased in comparison with the
      control group. CONCLUSION: La was accumulatied in the rat leg bones and the
      change of bone microstructure induced after the rats were fed with La(NO(3))(3)
      in low dosage for a long term.

PMID- 14710258
TI  - [Development of sustained release tablet of tamoxifen citrate and its in vitro
      release profile].
AB  - OBJECTIVE: To reduce the frequency of administration of tamoxifen citrate so as
      to improve its bioavailability and patients' compliance. METHODS: HPMC(K4M) was
      employed as major retarded-release controller. The wetting granulation and
      directly compressing method was used to produce the sustained release tablet.
      Then the in vitro release profile was applied as main criteria to evaluate six
      formulations according to the variation of HPMC(K4M) amount. The concentration of
      tamoxifen citrate was measured by UV spectrometry. Finally the releasing
      characteristics of sustained release and conventional tablets were compared to
      clarify the sustained effect of the former. RESULT: At 278 nm there was no
      interaction between tamoxifen citrate and the recipients so that it was adopted
      as the wavelength of determination. The recovery efficiency of this method ranged
      from 95%-105%. The final formulation could release 86.40% of its loading amount
      in 12 h and its releasing profile fitted the Zero-order equation well. The
      percentages of accumulative release in 1 h were 76.81% and 7.08% for sustained
      release tablet and conventional tablet respectively. CONCLUSION: The sustained
      release tablet of tamoxifen citrate could demonstrate a continuous and stable
      releasing profile and last for over 12 h. It has significant retarded effect in
      comparison with the conventional one and could be a new choice of regimen in its
      clinical application.

PMID- 14710259
TI  - [Cationic liposomes enhance the inhibitory effects of antisense
      oligodeoxynucleotide on hepatitis B virus].
AB  - OBJECTIVE: To study the interaction between 3beta-[N-(N', N'-dimethylaminoethane)
      carbamoyl] cholesterol (DC-chol), a cationic lipid, and antisense
      oligodeoxynucleotide (asODN), and the cytotoxicity to HepG(2) 2.2.15 cells and
      the inhibitory effects of asODN cationic liposomes on hepatitis B virus. METHODS:
      Extract efficiency was used to estimate the interaction between DC-chol and asODN
      under different conditions; MTT was applied to examine the infection of DC-chol
      concentration on the cytotoxicity of treated cells; By ELISA technology, we
      examined the contents of HBsAg, and HBeAg in the culture medium, and evaluated
      the accelerate efficiency of neutral liposome and cationic liposomes to the
      inhibitory effects of asODN on hepatitis B virus, and the infection of charge
      ratio on the inhibitory effects of asODN cationic liposomes. RESULTS: When the
      charge ratio >0.6, DC-chol could efficiently extract the asODN from the aqueous
      phase; The alkaline condition and the presence of Na(+), Cl(-) ions prevented the
      efficient interaction between DC-chol and the asODN; DC-chol cationic liposomes
      had some toxicity to HepG(2) 2.2.15 cells, at low concentration (0.84-26.94 mg x
      L(-1)), and the toxicity of DC/chol was linear with the concentration of DC/chol;
      Within 1.25-5.00 micromol x L(-1), the inhibition efficacy of asODN was
      correlated to its concentration; liposomes could enhance the inhibition efficacy
      of asODN on hepatitis B virus, and cationic liposomes could enhance much more
      (from 60% to 95%). CONCLUSION: Surface-modified DC-chol cationic liposomes can
      efficiently enhance the anti-hepatitis B virus efficiency of asODN in vitro.

PMID- 14710260
TI  - [Role of tissue factor in the invasive ability of cultured human colon carcinoma
      cells].
AB  - OBJECTIVE: To analyze the role of tissue factor (TF) in the in vitro invasive
      ability of human colon carcinoma cells (HT-29). METHODS: The eukaryotic
      expression vectors pcDNA3.1/Zeo bearing either sense or antisense TFcDNA were
      transfected into HT-29 cells by the way of lipofactamine 2000. TF proteins in
      transfected cells were detected by Western blot. In vitro Matrigel invasion
      assays were used to show the invasive ability of HT-29 cells with sense/antisense
      TFcDNA transfection. RESULTS: HT-29 cells with sense-TFcDNA transfection showed
      increased TF expression and invasive ability compared with the cells without
      transfection, but HT-29 cells with antisense-TFcDNA transfection got the contrary
      change. CONCLUSION: TF can increase the invasive ability of HT-29 cells in vitro.

PMID- 14710261
TI  - [Effect of recombinant human trefoil factor on protection of gastric mucosa and
      healing of chronic gastric ulcer in rats].
AB  - OBJECTIVE: To study the effect of recombinant human intestinal trefoil factor (
      rhITF) on the healing of rat chronic gastric ulcer, protect gastric mucosal and
      mechanisms are involved. METHODS: (1) Acute gastric mucosal injury was induced by
      ethanol, stress, aspirin and pylorusl ligation. The injury index,MDA,
      GMBL,hexosamine (Hex) and acid output were measure. (2) Chronic gastric ulcer was
      induced in rats by application of 50% glacial acetic acid to the serosa of the
      glandular stomach. After injury, rats received by rhITF or vehicle orally twice
      daily for 11 days. On day 12, gastric mucosal blood flow  GMBF   was measured
      under ether anesthesia. Then the pylorus was ligated for 3 hours and each stomach
      removed. The gastric acid output, ulcer index, Hex and nitric oxide(NO) content
      in gastric mucosa, as well as iNOSmRNA in the ulcer bed were determined. RESULTS:
      (1) rhITF protected gastric mucosa from the acute lesion, and increased Hex
      content in gastric mucosa. (2) rhITF treatment significantly decreased the ulcer
      index and gastric acid output, but increased the GMBF, Hex and NO content in
      comparison with the control groups. In addition, rhITF also stimulated iNOSmRNA
      expression in the ulcer bed by situ hybridization analysis. CONCLUSION: rhITF can
      protect gastric mucosa against acute lesion, and enhance the healing of chronic
      gastric ulcer in the rats. This action may result from the inhibition of gastric
      acid output, increase of GMBF.Hex and NO content and rhITF stimulated iNOSmRNA
      expression.

PMID- 14710262
TI  - [Application of combined epidural-spinal anesthesia in pediatric surgery and
      postoperative analgesia].
AB  - OBJECTIVE: To compare the anesthetic and analgesic efficacy of ropivacaine and
      bupivacaine and their side reactions in combined spinal-epidural anesthesia
      (CSEA) and postoperative analgesia in pediatric surgery. METHODS: Fifty children
      for lower abdominal surgery, aged 6-14 years, were randomly assigned to receive
      either ropivacaine (Group R, n=25) or bupivacaine (Group B, n=25) for CSEA.
      Spinal injection for Group R was a mixture of 1.5 ml of 10 g x L(-1) ropivacaine,
      0.5 ml distilled water and 1ml of 100 g x L(-1) dextrose. The injection for Group
      B was the same as that for Group R except 0.5 ml of 7.5 g x L(-1) bupivacaine.
      The terminal concentrations of anesthetics were 5 g x L(-1) for the two groups.
      The injection volume was calculated as: ml=(age x 0.2 + weight x 0.5) divided by
      2. When operations prolonged to 1.5 h, epidural infusion at the rate of 1 mg x
      (kg(-1) x h(-1)) started with 2.5 g x L(-1) ropivacaine for Group R and 2.5 g x
      L(-1) bupivacaine for Group B. The observed variables were the changes in blood
      pressure, heart rate, SpO(2), block level, visual analogue scores, and motor
      block. Epidural postoperative analgesia was performed for Group R with 100 ml of
      0.75 g x L(-1) ropivacaine to which 100 mg tramadol and 5 mg were added, and for
      Group B with 100 ml of 0.75 g/L(-1) bupivacaine instead. Backgroup infusion was 3
      ml x h(-1) for the children aged 6-9 years or 4 ml x h(-1) for the children aged
      10-14 years, bolus was 2 ml controlled by children or their parents when
      necessary, and locktime was 15 min. The observed variables were the efficacy of
      postoperative analgesia, recession of motor block of legs, and the incidence of
      headache, nausea and vomiting, leg numbness, and urinary retention within 24 h
      after operation. RESULTS: There was no significant difference between the two
      groups in block level. Motor block was much milder in Group R than that in Group
      B during operation, and recessed faster after operation. Only one case of nausea
      occurred in each group, and one case of urinary retention in Group B without
      statistical significance. CONCLUSION: Either ropivacaine or bupivacaine can be
      satisfactorily used in CSEA for analgesia during and after operation. However,
      ropivacaine has a weaker motor block than bupivacaine, which benefits early
      walking after operation and recovery of bowl movement.

PMID- 14710263
TI  - [Impact of nutritional status, inflammation and cardiovascular disease on the
      mortality of 90 Chinese peritoneal dialysis patients].
AB  - OBJECTIVE: To investigate the impact of nutritional status, inflammation and
      cardiovascular disease on the mortality of 90 patients with continuous ambulatory
      peritoneal dialysis (CAPD). METHODS: A cross-sectional study was performed in 90
      clinically stable CAPD patients. Patients' nutritional status (by SGA), chronic
      inflammation (by CRP), cardiovascular disease (CVD) were evaluated. All patients
      were followed for 24 months. RESULTS: Thirty-three of the 90 (36.67%) patients
      died during the follow-up, five patients transferred to hemodialysis and 3
      patients received transplantation. The causes of death were CVD in 12, infection
      in 13 and other causes in 7. Seventeen patients who died were malnourished.
      Malnourished patients had significantly higher mortality than well nourished
      patients (P<0.05). Patients with high serum CRP had higher mortality (P<0.01).
      CVD patients had also significantly higher mortality (P<0.01). The patients with
      malnutrition-inflammation-CVD (MIA) syndrome had significantly lower survival
      rate as compared with those with one or two components of MIA (P<0.01).
      CONCLUSION: During 2-year follow up, 45 percent of 90 CAPD patients left the
      program. The most common causes of death were CVD and infection. Half of the
      patients who died were malnourished. Inflammation, malnutrition and CVD may have
      aggravated each other, and contributed to the poor outcome of this patient
      population.

PMID- 14710264
TI  - [Effects of unilateral mandibular distraction osteogenesis on temporomandibular
      joint].
AB  - OBJECTIVE: To study the effects of unilateral mandibular distraction
      osteogenesis(MDO) on the temporomandibular joint(TMJ). METHODS: Ten rhesus
      monkeys were used to perform right MDO. After 5 days, latency period, the
      distractor was initiated at the rate of 0.5 mmx2/day, totally 15 days. When MDO
      completed, and 2,4,6,and 12 weeks after MDO, X-ray films of bilateral TMJ were
      taken and one group of animals was sacrificed. Bilateral TMJ were obtained and
      paraffin slices were made  HE and immunohistochemistry stains of TGF-beta1 were
      done on the slices. RESULTS: After MDO, the monkeys' mandible midline obviously
      deflected to the left side. The front teeth had open bite and reverse bite. The
      right molars were severely open bite and the left molars were reverse bite. From
      the X-ray film, we can see that the right condylar process moved backward and
      upward in the acetabulum, while the left condylar process moved forward and
      downward. On the slices, both sides of the TMJ showed different degrees of
      degeneration and proliferation, but the changes on the right side were more
      severe and obvious than the left side, and had involved all the cartilage's
      layers and the bone tissues under the cartilage. In some animals, there even
      appeared cartilage erosion and light histological changes of acetabulum. During
      the consolidation period, the open bite gradually closed, and the condylar
      process gradually moved to normal position. Twelve weeks after MDO, the open bite
      at the right side disappeared, but the front teeth open bite and reverse bite
      still existed. The right condylar process still lay a little backward and had
      some degree of degeneration. The left TMJ had the normal position and histology
      except for cartilage hypertrophy layer thickness. At different times during
      consolidation period, the positive stains of TGF-beta1 in condylar process on
      both sides were all more obvious than that of the control group. CONCLUSION: MDO
      can cause TMJ position change and light histological degeneration, but these
      changes can gradually rehabilitate in the future. TGF-beta1 may play a role in
      the reconstructive process of TMJ degeneration.

PMID- 14710265
TI  - [Cephalometric comparison of hard-tissue morphology between extraction and non
      extraction orthodontic treatment in borderline cases].
AB  - OBJECTIVE: To compare hard-tissue morphology by cephalometric measurements
      between extraction and non-extraction orthodontic treatment in borderline cases.
      METHODS: The samples consisted of 33 cases selected as borderline cases by 5
      orthodontic specialists. They were divided into 21 extraction cases (including 13
      four first premolar extraction cases and 8 second premolar extraction cases) and
      12 nonextraction cases by checking patients' treatment records. Conventional
      cephalometric analysis was made to compare hard tissue structures before and
      after orthodontic treatment and the same comparison was made between two
      different extraction patterns. RESULTS: No statistical difference was found on
      pretreatment hard-tissue morphology between extraction and non-extraction groups
      divided from borderline cases. The SNB angle of the four first premolars
      extraction group was smaller than that of the four second premolars extraction
      group by (4.0+/-1.3) degrees   P<0.01  . The statistical significant differences
      of the post-treatment hard-tissue cephalometry between extraction and
      nonextraction and between two different extraction patterns were found to be
      limited to the items related to the tooth position. CONCLUSION: Conventional
      cephalometric analysis cannot differentiate extraction or non-extraction
      treatment selection from borderline cases. The differences between extraction and
      non-extraction orthodontic treatments were limited to tooth positions but had no
      skeletal relation. Extraction of the four second premolars could prevent upper
      incisors from uprighting as it often follows the four first premolar extraction
      treatment. Extraction of the four first premolars could change the incisor
      position much more than extraction of the four second premolars. The changes of
      four second premolar extraction treatment were much similar to non-extraction
      treatment.

PMID- 14710266
TI  - [Computer tomograghy study on periodontal patients with anterior displaced teeth
      before and after combined orthodontic-periodontal treatment].
AB  - OBJECTIVE: To evaluate evaluation of the changes of alveolar bone height in the
      periodontal patients with anterior teeth displacement before and after combined
      orthodontic-periodontal treatment with circumferential fibrotomy. METHODS:
      Totally 16 periodontal patients with anterior displaced teeth were analyzed after
      random clinical trialed as groups with and without circumferential fibrotomy of
      involving teeth followed by orthodontic intrusion. Evaluations of the changes of
      alveolar bone were given before and after treatment by means of periapical X-ray
      film and CT scan of the involving teeth. RESULTS: Orthodontic treatment with
      circumferential fibrotomy can increase the height of crest bone. Alveolar bone
      height was increased in the patients with circumferential fibrotomy followed by
      orthodontic intrusion of displaced anterior teeth. Alveolar bone height was
      increase by 1.2 mm on average in circumferential fibrotomy patient. In the
      patients with symmetric alveolar bone loss, 0.8 mm increase of alveolar bone
      height was observed following treatment. For the patients with asymmetric
      alveolar bone loss, 0.9 mm increase of alveolar bone height was detected in mild
      bone loss patients, but 1.4 mm and 2.2 mm increase of alveolar bone height were
      found in moderate and severe bone loss patients, respectively. For patients
      having the orthodontic treatment without circumferential fibrotomy, the alveolar
      bone height was increased by 0.1 mm only. Statistic significance was found
      between the circumferential fibrotomy group and non-fibrotomy group. CONCLUSION:
      Combined orthodontic-periodontal treatment with circumferential fibrotomy could
      correct the malpositioned teeth, and improve the periodontium conditions and gain
      the crest bone.

PMID- 14710267
TI  - [Changes of upper airway morphology induced by mandibular advancement in patients
      with obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To determine the changes of upper airway morphology induced by
      mandible position from central relation to advancement position in patients with
      obstructive sleep apnea syndrome. METHODS: Nineteen patients (17 males and 2
      females) suffering from obstructive sleep apnea syndrome were confirmed with
      polysomnography. Occlusal wax record was made with mandible in advancement
      position. Helical computed tomography was performed on each patient in central
      relation and mandibular advancement position with wax record in situ
      respectively. On each slice, anteroposterior and transverse diameters were
      obtained. Airway shape was expressed as the anteroposterior/transverse (AP/T)
      diameter ratio. Paired-samples t test was employed to compare the measurements.
      RESULTS: With mandibular advancement, average and minimal diameters of
      glossopharynx and hypopharynx were increased significantly. Compared with it, the
      change of transverse diameter was more prominent. All segments of upper airway
      were increased significantly except hypopharynx laterally. Moreover, the change
      of velopharynx shape was observed on axial planes. Ellipse with transversal long
      axis became more compressed. CONCLUSION: Upper airway morphology of all segments
      was influenced by mandibular advancement whether in the sagittal or transverse
      plane of space, or airway shape. Not only anatomic connection but also regulation
      of the nerve system and other still unknown mechanism make contribution to the
      changes of upper airway morphology in patients with obstructive sleep apnea
      syndrome. The changes of upper airway morphology above mentioned constitute the
      rationale of treatment of obstructive sleep apnea syndrome with oral appliances.

PMID- 14710268
TI  - [Calprotectin and total protein in gingival crevicular fluid during experimental
      gingivitis].
AB  - OBJECTIVE: To measure GCF calprotectin and total protein for evaluating whether
      the calprotectin could be a sensitive marker for the initial inflammation of
      gingiva. METHODS: Eleven young male subjects with healthy gingiva, who had no
      systemic diseases, were selected for this study. GCF samples (4 teeth /person)
      were collected with strips of filter paper at baseline (0 day), on the 7 th, 14
      th, 21 st days (without oral hygiene), and 28 th day (7 days after reestablishing
      oral hygiene) during experimental gingivitis. The amount of calprotectin was
      measured by ELISA. The amount of total protein was assessed with protein-dye
      binding assay. RESULTS: The amount of calprotectin increased during the
      experimental gingivitis, and reached the highest level on the 21 st day. After
      oral hygiene was reestablished it reduced to the level of baseline. The amount of
      total protein had the same tendency as calprotectin. CONCLUSION: The amount of
      calprotectin and the total protein in GCF can reflect the initial inflammation of
      gingiva.

PMID- 14710269
TI  - The burden of infections and child health in Iraq.

PMID- 14710270
TI  - Extraction of urinary bladder stone as described by Abul-Qasim Khalaf Ibn Abbas
      Alzahrawi (Albucasis) (325-404 H, 930-1013 AD). A translation of original text
      and a commentary.
AB  - This is a detailed study of the technique of cystolithotomy as practiced by the
      Muslim surgeon Alzahrawi (Albucasis) in Cordova more than 1000 years ago. In
      addition to translating the relevant chapter in his book Al-Tasreef, his
      technique is critically evaluated comparing it with that of his predecessors and
      his successors. The study confirmed the originality of Alzahrawi who described
      operative steps and invented operative instruments not known in the Greco-Roman
      era. He was also the first to describe, in details, the operative technique in
      women and to recommend the 2-stage operation in complicated cases. His
      modifications and innovations greatly influenced surgery in Middle Ages Europe up
      to the 18th century which witnessed the beginnings of the modern method using the
      suprapubic, instead of the perineal, approach. Alzahrawi's influence is vividly
      seen in the practice of the Italian lithotomist "Marianus Sanctus" (16th
      century), the French "Jack De Beaulieu" (17th century) and the English "Shelsden"
      (18th century). Alzahrawi is the founder of lithotripsy. He introduced Al
      Kalaleeb forceps to crush large bladder stones and Al-Mishaab to drill and
      fragment an impacted urethral stone. Andreas a Cruce (18th century) only added
      screw action to Al-Kalaleeb lithotrite but Amussat managed in 1822 to apply it
      transurethrally. Similarly, by the notion of transurethrally getting at the stone
      while within the bladder, Alzahrawi's idea of drilling by Al-Mishaab was the
      foundation of the litholepte of Fournier de Lempdes (1812), the instrument of
      Gruithusien (1813), Civiale's trilabe (1818) and the brise coque of Rigal De
      Galliac (1829).

PMID- 14710271
TI  - Ambulatory blood pressure monitoring. A pediatric review.
AB  - Hypertension is one of the major contributors to cardiovascular, renal and
      central nervous system morbidity and mortality. Although it is more prevalent in
      the adult population, hypertension and its sequelae are being seen in the
      pediatric population with increasing frequency. Blood pressure (BP) is not a
      static phenomenon. It is highly variable, changing constantly in response to
      various activities, stimuli, and stresses. Consideration of all of these factors
      make intermittent clinic BP measurements less effective in accounting for BP
      rhythmicity so ambulatory BP monitoring has emerged as a useful tool to give a
      detailed analysis of BP patterns during the day and night. It is becoming more
      and more evident that ABPM could be a useful tool in evaluation of white coat
      hypertension, apparent drug resistant hypertension, to evaluate efficacy of
      medications for control of hypertension, in evaluation of borderline
      hypertension, to further elaborate on chronology of hypertension and above all to
      assess the end organ damage risk as measurement of 24 hour BP parameters do
      correlate with hypertensive end organ injury.

PMID- 14710272
TI  - Non-Langerhan's cell histiocytoses of the skin.
AB  - Histiocytic proliferations may be reactive or neoplastic. The neoplastic
      proliferations (histiocytoses) are subdivided into a few categories. One of these
      categories is the non-Langerhan's cell histiocytoses (NLCH). Cutaneous NLCH is a
      heterogeneous collection of conditions which can be sub grouped on the basis of
      the morphological appearance of the lesional histiocyte into xanthomatized,
      oncocytic, vacuolated, spindle-cell and polymorphous subtypes. The clinical
      characteristics and histological appearances of a variety of conditions within
      each subtype are discussed.

PMID- 14710273
TI  - Disease burden and case management of bacterial meningitis among children under 5
      years of age in Saudi Arabia.
AB  - OBJECTIVE: This study was designed to explore the case management and disease
      burden of bacterial meningitis among children below the age of 5 years in the
      Kingdom of Saudi Arabia. METHODS: A prospective descriptive study was conducted
      during June 1999 through to May 2001 in 8 hospitals from 5 cities in different
      areas of the country. Those were, King Fahad Specialist Hospital and Maternity &
      Children Hospital, Buraidah, Belgorashi General Hospital and King Fahad
      Specialist Hospital, Al-Baha, Maternity & Children Hospital and Ohud Hospital, Al
      Madina, Al-Qatif General Hospital in the Eastern Region and Prince Abdulrahman
      Bin Ahmed Alsudairy Central Hospital, Sakaka. The study population was 171,818
      children under the age of 5 years. RESULTS: During the study period 208 cases of
      bacterial meningitis were identified, 141 (67.8%) with a definite causative
      organism: Hemophilus influenzae type b, Neisseria meningitidis, Streptococcus
      pneumoniae and other bacterial species. The remaining 67 cases (32%) were labeled
      as aseptic meningitis. A considerable proportion of cases was found to have
      received an antibiotic prior to presentation. While symptoms such as fever or
      poor feeding were common among cases, meningeal signs were less prominent. A
      lumbar puncture was carried out on all cases to reach diagnosis by gram stain,
      latex agglutination test and cerebrospinal fluid (CSF) and blood cultures
      following standard procedures. The immediate burden of meningitis cases was found
      to be the lengthy stay of patients in the hospital wards and intensive care
      units. Some of the main causative agents were resistant to the conventional
      antimicrobial therapy, but susceptible to newer antibiotics. CONCLUSION: The
      study being based on a population based surveillance gave a better overview on
      causative organisms of meningitis emphasizing that Gram stain, serology of CSF
      and culture (of CSF and blood) should be used. A high index of suspicion is
      needed to diagnose meningitis in children. Lumbar tap should be encouraged and
      supported in terms of training and more authorization to apply in diagnostic
      tests of such conditions. Audiometric measurement is a crucial need in the
      assessment of meningitis cases and in the process of their follow up. This type
      of service is clearly missing in our system. Influential steps are to be planned
      to avail this service.

PMID- 14710274
TI  - Prevalence of H.influenzae biotypes and their clinical significance in a
      University Hospital.
AB  - OBJECTIVE: Hemophilus influenzae is an important pathogen that is responsible for
      invasive and non-invasive infections in both children and adults. This study aims
      to assess the relationship of biotypes to the sites of infection, serotypes,
      antimicrobial susceptibility, beta-lactamase production and age. METHODS: A total
      of 200 isolates of H.influenzae were obtained from clinical specimens over a
      period of 12 months from January 2001 through to January 2002 from King Abdul
      Aziz University Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: Most of the
      strains were non-typable and were isolated from patients with non-invasive
      infections. The typable isolates from invasive infections mostly serotype b were
      isolated from blood, cerebrospinal fluid and hip joint aspirate. Biotype II
      accounted for 37% of the isolates followed by biotypes III and I (29.5% and 23%).
      The remaining 10.5% were made up of biotypes IV, V, VI and VII. A significantly
      high resistance to cotrimoxazole (33.5%) and ampicillin (19%) was observed. Two
      point five percent of the isolates were resistant to chloramphenicol. All the
      isolates resistant to ampicillin were beta-lactamase producers and susceptible to
      cefuroxime, ceftriaxone, ciprofloxacin and rifampicin. CONCLUSION: This study
      revealed that biotypes II and III are the predominant biotypes of H.influenzae
      found in non-invasive infections. There is an apparent relationship between
      biotype and site of infection which could be useful as an epidemiological marker.

PMID- 14710275
TI  - MRSA prevalence in a teaching hospital in Western Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of Methicillin Resistant Staphylococcus
      aureus (MRSA) colonization in our institution. METHODS: A 5-day period prevalence
      study of all adult and pediatric patients. Excluded areas were the adult
      intensive care unit (screened on admission and weekly thereafter), the outpatient
      hemodialysis population (screened monthly), and newborns. Our facility is a
      referral/teaching hospital for the National Guard population and their dependants
      in Western Saudi Arabia. A total of 240 patients were screened. Nasal sampling
      was carried out and isolation/identification of MRSA was performed using standard
      microbiological methods. RESULTS: The total number of patients sampled was 240
      and of those 10 (4%) were colonized. The 10 positives were found in 4 patient
      care areas; adult male medicine 5, adult male oncology 3, adult female medicine
      one, adult high dependency unit one. These patients care areas had 69 patients
      (42 males and 27 females). Ten (14%) were colonized by MRSA; 9 males (21%) and
      one female (3%). Statistical analysis Chi Square for discontinuous variables, "F"
      test for continuous variables found that one), male gender (p=0.04), 2) the
      presence of a long term invasive device (p=0.04), 3), length of stay (p=0.004)
      were predictive of MRSA colonization. CONCLUSION: The overall prevalence of MRSA
      colonization in our hospital was low, however a sub-segment of the population
      identified as male, having long term invasive devices, and hospitalized more than
      2 weeks, were frequently colonized. Any strategy, in our hospital, to control the
      spread of MRSA should include the testing of this population.

PMID- 14710276
TI  - A comparative study on the application of 3 molecular methods in epidemiological
      typing of bacterial isolates using MRSA as a prototype.
AB  - OBJECTIVE: To evaluate and compare 3 widely used molecular techniques, namely,
      restriction endonuclease analysis of plasmid deoxyribonucleic acid (REAP),
      randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis
      (PFGE) for their suitability and usefulness in the typing and fingerprinting of
      bacterial isolates. METHODS: Twenty-four epidemiologically unrelated methicillin
      resistant Staphylococcus aureus (MRSA) isolates were used to evaluate the
      molecular typing methods (REAP, RAPD and PFGE). The study was conducted at the
      Research and Diagnostic Laboratories of King Faisal Specialist Hospital and
      Research Center from January 2002 through January 2003. RESULTS: Only 20.8% of
      all isolates studied were of the same genotypes by all 3 methods. Two major
      clusters of strains each representing 33% of the total number of isolates were
      identified by REAP analysis. Each of RAPD and PFGE however, identified one major
      cluster represented by 54% and 83% of the total number of isolates, all 3 typing
      methods, therefore, showed the clonal genetic relatedness among distant MRSA
      isolates. However inter-strain comparison of fingerprint data generated from each
      method revealed differences in clonal representation of the MRSA isolates.
      CONCLUSION: Although a variety of molecular assays are available for typing of
      bacterial species, there is no single standardized protocol for routine analysis.
      Reproducibility and interpretation of genotypic data are therefore, highly
      dependent on methodologies employed by the individual laboratory. Our findings
      illustrate the importance of using a combination of methods in typing schemes of
      bacterial isolates. In terms of reproducibility and typeability we found that
      PFGE is superior to REAP and RAPD and, therefore, more suitable for routine,
      standardized tracing of nosocomial bacterial isolates.

PMID- 14710277
TI  - Tetanus experience in a public hospital in Western Saudi Arabia.
AB  - OBJECTIVE: Tetanus although rare, has not been eradicated and continues to
      present from time to time. Early diagnosis and management may be life saving.
      This study aims to evaluate all patients admitted with clinical diagnosis of
      tetanus in King Abdul-Aziz Hospital Jeddah, Kingdom of Saudi Arabia over the last
      3 years. METHODS: All patients admitted with clinical diagnosis of Tetanus in
      King Abdul-Aziz Hospital and Oncology Center from January 2000 through to
      December 2002 were retrospectively reviewed and data was analyzed to determine
      the demographic features, clinical details, management, and outcome of treatment.
      RESULTS: A total of 11 patients were admitted during this period. All patients
      were diagnosed in emergency room by clinical examination. Their ages ranged from
      22-68 years. The immunization status of these patients was unknown. All of them
      were males with 4 of them being injection-drug users. Eight patients had a
      definite history of injury mainly involving the lower limbs. The incubation
      period ranged from 5-30 days. Nine patients required mechanical ventilation for a
      period varying from 2-4 weeks. All patients received Tetanus Immunoglobulin with
      a dose ranging from 500-3000 unit. The spasms were mainly controlled by diazepam
      infusion with a maximum dose of 480mg/day. Magnesium sulphate was used in 6
      patients to control spasms and autonomic dysfunction. Metronidazole was used in
      addition to benzyl penicillin in 9 patients. Out of the 11 cases 10 were
      discharged home and only one patient died 6 days after admission. CONCLUSION:
      Tetanus is still a problem in developing countries. It is a potentially fatal
      disease, without early medical intervention. Primary immunization and scheduled
      booster immunization are important preventive measures that have greatly reduced
      the incidence of tetanus.

PMID- 14710278
TI  - Prevalence of gestational trophoblastic disease. A single institution experience.
AB  - OBJECTIVE: To study the incidence and time trends of gestational trophoblastic
      disease in the Kingdom of Saudi Arabia (KSA). METHODS: A retrospective study of
      medical records of 64,762 pregnancies registered and treated at Security Forces
      Hospital, Riyadh, KSA, from January 1988 through to December 1998. RESULTS: Fifty
      nine cases of hydatidiform mole (36 complete hydatidiform mole (CHM) and 23
      partial hydatidiform mole (PHM) and 2 cases of choriocarcinoma were observed, out
      of 64,762 pregnancies registered at Security Forces Hospital, Riyadh, KSA, during
      an 11 year period. The temporal trends exhibited significant reduction in the
      incidence of GTD during the study period. CONCLUSION: The incidence of GTD has
      declined with the rapid socio-medical development of the KSA, and is now
      comparable to that of Europe. The optimal management of this disease depends on
      prompt diagnosis, correct stratification of the risk category and appropriate
      treatment using various modalities such as chemotherapy and surgery.

PMID- 14710279
TI  - Clinical profile of patients operated for benign adnexal tumors and the
      histopathological types.
AB  - OBJECTIVE: To study the clinical presentation of patients with benign adnexal
      tumors who had surgical management and the histopathological types of the tumors.
      METHODS: Retrospective data were collected on 110 patients who underwent surgery
      for benign adnexal tumor from January 1999 through to April 2002, in Sultan
      Qaboos University Hospital, Sultanate of Oman. The histopathological types of the
      tumors were also studied. RESULTS: Abdominal pain was the commonest presenting
      symptom in 65% of the patients followed by abnormalities of vaginal bleeding.
      Most of the patients were managed by laparotomy and ovarian cystectomy. The
      commonest histopathological type was benign mature teratoma in 28% of the
      patients. CONCLUSION: Benign mature teratoma was the commonest histopathological
      type. Most of the patients had laparotomy; ovarian cystectomy and recurrences
      were few.

PMID- 14710280
TI  - Study of pelvicaliceal anatomy by helical computerized tomography. Is it
      feasible?
AB  - OBJECTIVE: To evaluate the role of 3-dimensional images produced by computerized
      tomography (CT), using intravenous contrast to study pelvicaliceal anatomy. This
      might be of help in endourological procedures. METHODS: The study was conducted
      in King Fahd Hospital of the University, King Faisal University, Dammam, Kingdom
      of Saudi Arabia. The study took place from July 2002 through to October 2002.
      Helical CT was carried out for patients who were investigated using excretory
      urography for any reason, after obtaining a written consent. A CT was carried out
      to the kidneys only within 10 minutes (between the 5 and 15 minute films of
      excretory urography). Images were reprocessed by 3-dimension construction after
      subtracting all structures except for the pelvicaliceal system. Thirty-six normal
      kidneys were studied. RESULTS: The upper pole was drained by a single caliceal
      infundibulum in all 36 (100%) kidneys. The middle segment of the kidney was
      drained by 2 infundibula in 32 (89%) kidneys. Four (11%) kidneys had no middle
      caliceal infundibula. The lower pole was drained by 2 caliceal infundibula in 23
      (64%) and a single infundibulum in 13 (36%) kidneys. The minor calices draining
      each renal segment were seen clearly. CONCLUSION: Three-dimensional images
      derived by helical CT are feasible for evaluating the anatomy of pelvicaliceal
      system, and, can be of help in endourological procedures.

PMID- 14710281
TI  - A formula for the estimation of the body surface area of Saudi male adults.
AB  - OBJECTIVE: Human body surface area (BSA) is the preferred denominator for
      physiological indices of body metabolism and for drug dosages. The Du Bois and Du
      Bois height/weight nomogram, used for fast and convenient estimation of patients
      BSA, is not suitable for all populations due to ethnic differences in body shape
      and build. The purpose of this study was to obtain direct measurements of BSA and
      use the data to construct a prediction formula for Saudi male adults. METHODS:
      Body surface area was measured in 21 adult male Saudis at Assir Central Hospital
      in Abha, Kingdom of Saudi Arabia between 2000 and 2003, using a coating
      technique. Areas of the coating material were determined with a compensating
      planimeter. Other anthropometric indices were measured or calculated according to
      standard procedures. Measured values of BSA were subjected to linear regression
      analysis using the least squares method to obtain a formula for predicting BSA
      from heights and weights. RESULTS: Mean body mass index (BMI) was 25.1 +/- 1.6
      kg/m2; linearity, 2.46 +/- 0.13 cm/kg; surface to mass ratio, 0.025 +/- 0.0008
      m2/kg; relative sitting height (RSH), 0.51 +/- 0.005. The closest fit to measured
      BSA values was given by the biexponential regression equation: BSA=0.02036 x
      H(0.516) x W(0.427) +/- 0.01283. This formula predicts BSA of Saudi male adults
      more accurately than all existing equations tested and yields a convenient BSA
      table for Saudis. CONCLUSION: The use of our formula, with prediction accuracy
      superior to those of existing formulae, should facilitate the establishment of
      normal values of other physiological indices. It should also lead to more
      reliable and precise drug dosages and expedite rapid decision making in critical
      care situations.

PMID- 14710282
TI  - Dental health status and caries pattern of preschool children in Al-Kharj, Saudi
      Arabia.
AB  - OBJECTIVE: The objective of this study was to assess dental caries and its
      relation to plaque, tooth brushing habit and past dental attendance, and to
      determine the caries pattern in primary dentition of preschool children. METHODS:
      One hundred and three, 5-year-old children, from preschool nurseries in Al-Kharj,
      Kingdom of Saudi Arabia were studied in 1994. The World Health Organization
      criteria was used to determine caries. RESULTS: Only 16.5% were caries free. The
      mean decayed missing filled teeth (dmft) was 7.1, and by excluding caries free
      children it was 8.5. The decay component of dmft was predominant (82%). Almost
      90% of the children had plaque present on their teeth and one-third never brushed
      their teeth while two-thirds had never been to a dentist. All children who never
      brushed their teeth had plaque and caries. Molars were the teeth, which were most
      frequently carious, and caries among all teeth was always bilateral. CONCLUSION:
      There was high prevalence of untreated caries and high dental needs with
      concomitant poor dental health among these preschool children.

PMID- 14710283
TI  - The effect of unilateral partial edentulism to muscle thickness.
AB  - OBJECTIVE: Teeth and muscles play a very important role for occlusal equilibrium
      and function. When tooth loss begins, it may also affect the function of the
      muscle tissues. METHODS: The thickness of the masseter and anterior temporalis
      muscles were measured bilaterally in 30 healthy fully dentate adults and in 30
      unilateral edentulous patients by using ultrasonographic imaging. All scans were
      carried out by the same radiologist to eliminate the inter-observer difference,
      using a real time scanner (Toshiba SSA- 270 A Japan). A 7.5 MHz linear transducer
      was used. The transducer was held against the cheek with light pressure. The
      effect of age, sex, duration of the partial edentulism, unilateral chewing habits
      of the individuals to the muscle thickness were also evaluated. In all subjects,
      facial proportion index was also determined. RESULTS: No study has been found in
      the literature concerning the masticatory muscle thickness in unilateral partial
      edentulous patients. Therefore, the main purpose of this study was to compare and
      establish the differences of the muscle thicknesses between dentate and
      edentulous sides in unilateral partial edentulous patients with ultrasonography
      and to test whether the variation in the thickness of the muscle is related to
      the variation in the facial morphology using the facial proportional indices in
      the study groups. In the present study, ultrasonography revealed a large
      variation in the thicknesses of the masseter and temporalis muscles in
      experimental and control groups, during both relaxed and contracted conditions.
      The thicknesses of the muscles in females during both relaxed and contracted
      conditions were less than those in males in both control and experimental groups.
      In experimental group, a high negative correlation was found between the
      thickness of the masseter muscle and Facial proportion Index (FPI) in females,
      however, the statistical analysis showed no significant difference in males.
      Also, a high negative correlation was found in control group, especially in
      females. There was no statistically significant relationship between thicknesses
      of the muscles and age of the subjects in both groups. There was no statistically
      significant relationship between unilateral chewing habits and muscle thickness.
      In this study, the duration of partial edentulism did not affect the thickness of
      the muscles. CONCLUSION: Further research is required to study muscular atrophy
      for comparison with total edentulism.

PMID- 14710284
TI  - Malignant biliary strictures. Diagnosis and management.
AB  - OBJECTIVE: To identify the cause, methods of diagnosis and management of
      malignant biliary strictures in our institution and compare with studies from
      other communities. METHODS: From March 1998 through to August 2002, we reviewed
      1000 files of patients who underwent endoscopic retrograde
      cholangiopancreatography (ERCP) at the Gastroenterology unit, King Khalid
      University Hospital in Riyadh, Kingdom of Saudi Arabia for malignant biliary
      strictures (MBS). Clinical, laboratory data, method of diagnosis and management
      were recorded. RESULTS: Seventy-two patients (72/1000) with MBS were encountered.
      Forty one (57%) were males and 31 (43%) were females and the majority were Saudi
      nationals (82%). Jaundice and right upper quadrant pain were the most frequent
      symptoms in 84.7% and 52.8% of patients. Cholangiocarcinoma was present in 31
      (43%) and pancreatic adenocarcinoma in 23 (31.9%) patients. Other malignancies
      found included gallbladder carcinoma in 5 patients (6.9%), ampullary carcinoma in
      5 (6.9%), metastatic liver carcinoma in 4 patients (5.6%), hepatocellular
      carcinoma in 2 (2.8%) and lymphoma in 2 (2.8%). The diagnosis was entertained
      mainly by ERCP (93%). Endoscopic palliation was carried out in 77.8% of patients,
      percutaneous transhepatic drainage in 13.9% and surgery in 6 (8.3%). The mean
      survival was higher for the endoscopic compared to the percutaneous transhepatic
      and surgery groups (6.9 +/- 4.13, 4.27 +/- 4.29 and 3.67 +/- 2.65 months).
      CONCLUSION: In non-resectable tumors, ERCP is the optimal method of diagnosis and
      palliation of MBS.

PMID- 14710285
TI  - Gastroesophageal reflux in bronchial asthma patients. A clinical note.
AB  - OBJECTIVE: The objective is to correlate the symptoms of gastroesophageal reflux
      with the results of esophageal reflux with the results of esophageal pH metry in
      asthmatic patients. METHODS: A prospective study was carried out in King Fahd
      Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia (KSA), during the
      period January 2000 through to February 2001, whereby 50 patients (34 females and
      16 females) with primary diagnosis of bronchial asthma were consecutively
      enrolled, their mean age + SD was 38.01 + 9.8 years. Twenty-two subjects who were
      not suffering from asthma or gastroesophageal reflux (GER) (13 females and 9
      males) constituted the control group. A questionnaire was administered to all
      participants and demographic data; asthma and GER symptoms were obtained.
      Esophageal manometry was performed, whereby the location, length and resting
      pressure of the lower esophageal sphincter (LES) were determined, pH catheter was
      inserted nasogastrically, and ambulatory pH data over 24 hours were collected.
      Pulmonary function tests were also performed. RESULTS: Twenty-two (44%) patients
      with asthma had a Demeester score greater than 14.7 and were therefore diagnosed
      as having pathological GER. Accordingly, the asthma patients were divided into 2
      groups, asthma patients with GER (n=22) and those without GER (n=28). Multiple
      logistic regression analysis revealed that age did not significantly influence
      occurrence of GER, but it indicated that hoarseness of voice and nocturnal
      symptoms were significant predictors for the presence of GER in asthmatic
      patients, hence, the probability of having GER in an asthma patient is nearly 8
      times if he/she has nocturnal symptoms and about 7 times if they have hoarseness
      of voice. However 36.4% of asthmatic patients diagnosed by esophageal ph metry as
      having GER did not complain of heartburn and hoarseness of voice; such as the
      reflux was silent. CONCLUSION: The frequency of GER among 50 patients with asthma
      reporting to KFHU, Al-Khobar, KSA is 44%. The presence of nocturnal symptoms and
      hoarseness of voice are significant clinical predictors of GER in asthmatic
      patients. Patients with difficult to treat asthma should be subjected to
      esophageal pH metry since a substantial proportion of them may have silent
      reflux.

PMID- 14710287
TI  - Predictors of neonatal mortality in the intensive care unit in Abha, Saudi
      Arabia.
AB  - OBJECTIVE: Based on 11 months of prospective surveillance in the neonatal
      intensive care unit (NICU) of Abha General Hospital, Abha, Kingdom of Saudi
      Arabia, The association of neonatal morbidity and mortality with different risk
      factors were studied for prediction of different factors of mortality. METHODS:
      All neonates admitted to the ICU during the period of study; April 2002 through
      to February 2003 were included. They were followed until discharge or death.
      RESULTS: Of the 277 infants admitted, 62 died (22.4%). The 3 common illnesses
      were prematurity with respiratory problems (31%), respiratory distress syndrome
      (27%) and perinatal asphyxia (7.6%). Sixty one percent of deaths occurred within
      the first 3 days, while only 3.2% died after the first month. Fifty-five percent
      of admission were premature; the percent of mortality among them was 35%. Those
      who were delivered before 30 week constituted 13% with a very high case fatality
      rate, 86%. Multivariate analysis revealed that gestational age, severity of
      illness, Apgar score <7 at 5 minutes (asphyxia) and mechanical ventilation were
      the most important predictors of mortality. CONCLUSION: Mortality in the NICU is
      high, these results suggest more effort is needed to identify and reduce risk
      factors associated with neonatal mortality with special emphasis on prematurity,
      and to evaluate medical care provided in NICU.

PMID- 14710286
TI  - Lack of association of coronary artery disease with H.pylori infection.
AB  - OBJECTIVE: It has been suggested from previous studies that there is an
      associated increased risk of coronary artery disease (CAD) in patients with
      Helicobacter pylori (H.pylori). However, others dispute this. We therefore
      evaluated this hypothesis in a group of patients with confirmed H.pylori
      infection. METHODS: A total of 158 patients with dyspeptic symptoms were
      evaluated by esophago-gastro-duodenoscopy (EGD) in King Khalid University
      Hospital in Riyadh, Kingdom of Saudi Arabia from May through to June 1997.
      Endoscopic biopsies and histology as well as culture and serology for H.pylori
      were obtained. In patients with confirmed H.pylori a further analysis was
      performed looking at associated (CAD) or known risk factors for CAD. RESULTS:
      Among the 158 patients who underwent EGD, 143 patients (90.5%) were found to have
      H.pylori either by culture, histology or serology, or both in a percentage of
      (31.5%) (77.6%) and (60.8%). There was no evidence of CAD in this group of
      patients based on history, electrocardiogram (ECG), echocardiography, ECG stress
      test, dypiridamole thallium scan or coronary angiography. Other known risk
      factors for CAD were cigarette smoking (12.6%), diabetes mellitus (10.5%),
      hypertension (1.4%) and hyperlipidemia (2.8%). CONCLUSION: Helicobacter pylori
      infection does not increase the risk of CAD, and should not be considered as an
      independent risk factor for CAD. Further, prospective large trial is needed to
      confirm our finding.

PMID- 14710288
TI  - Idiopathic granulomatus lobular mastitis. A forgotten clinical diagnosis.
AB  - OBJECTIVE: To review clinicopathological features of all cases diagnosed as
      idiopathic granulomatous lobular mastitis (IGLM) in our hospital and compare them
      with other data from the Kingdom of Saudi Arabia. METHODS: Reports of all breast
      specimens received in histopathology laboratory in Qatif Central Hospital,
      Kingdom of Saudi Arabia over a 14 year period (1988 through to 2002) were
      collected and those diagnosed as IGLM were selected for analysis of both
      pathological material and clinical data. RESULTS: Eleven patients representing
      1.6% of all breast specimens were diagnosed as IGLM. The mean age was 35 years
      (range 25-50). Both breasts were equally affected. The most frequent presenting
      symptom was a breast mass of 2-22 weeks duration. The most common clinical
      diagnosis was chronic abscess (5 patients). Relation to pregnancy, lactation or
      oral contraceptives pills was elicited in 4 patients. Recurrence at different
      time intervals occurred in 3 patients. Microscopically there was an evident
      granulomatous inflammation mostly in lobular distribution. Ductal inflammation
      with epithelial changes was noted in most cases. Staining and cultures were
      negative for both mycobacterium and fungal organisms. CONCLUSION: Granulomatous
      mastitis is not unheard of and clinicians should keep it in their list of
      differential diagnosis of breast lumps so appropriate handling of breast
      specimens including microbiological studies can be pursued. Utility of fine
      needle aspiration biopsy as a diagnostic tool is to be considered.

PMID- 14710289
TI  - Skin cancers in Western Saudi Arabia.
AB  - OBJECTIVE: A retrospective analysis of skin cancers in a major referral centre in
      Taif region, Kingdom of Saudi Arabia, (KSA). METHODS: The case records of all
      malignant skin cancers diagnosed during a 10 year period, from 1992 through to
      2001 were taken for the study. The clinical and histopathological details were
      noted. These were compared to reports from the rest of KSA and other countries.
      RESULTS: One hundred and four cases of malignant skin lesions including primary
      and metastatic tumors were seen. The majority were Saudis. The male to female
      ratio was 2.25:1. Most of the patients were over the age of 60 years. Basal cell
      carcinoma was the most frequent (51%) followed by squamous cell carcinoma (26%)
      and malignant melanoma (12.5%). Other rare primary tumors were those arising from
      the skin appendages, dermatofibrosarcoma protuberans and Kaposi's sarcoma.
      Metastatic skin lesions were seen in 5; in one it resulted from a surgical
      procedure and in the others the primary site could not be determined. CONCLUSION:
      The number of patients seen in this report is not high indicating that protective
      factors like clothing and skin type of the individual played a protective role.
      However, we feel that more studies should be encouraged in other regions along
      with the creation of a registry within each area to monitor the information
      regarding skin cancers. This could then be incorporated in health education
      programmes to be imparted to the public.

PMID- 14710290
TI  - Mesenteric cystic teratoma in children.
AB  - Mesenteric teratoma is an extremely rare tumor, arising, akin all other
      teratomas, from totipotent primordial cells and displays a mixture of tissues of
      tridermal or bidermal origin. Two cases of mature mesenteric teratoma in a 5
      month-old girl and a 4-month-old boy, the youngest reported in the literature,
      excluding a case recently diagnosed prenatally, are described. Diagnostic tools,
      differential diagnosis and management are also discussed.

PMID- 14710291
TI  - A case of rifampicin induced pseudomembraneous colitis.
AB  - We report a case pf pseudomembranous colitis that developed in a patient with
      tuberculous abdominal lymphadenopathy during treatment with rifampicin. The
      patient had delayed presentation (3 months) after the start of rifampicin. She
      had one relapse after 2 months that was successfully treated, and she finished
      her antituberculosis therapy without any further relapses. Awareness of this
      serious complication of rifampicin therapy should be encountered.

PMID- 14710292
TI  - Necrotizing fasciitis complicated by multiple pneumoceles.
AB  - This paper reports a 14-year-old male patient who developed necrotizing fasciitis
      of the leg after a minor trauma. He was admitted to our intensive care unit with
      septic shock and acute lung injury. The clinical course was complicated by
      bilateral multiple pneumoceles resulting in bilateral pneumothoraces. The
      causative organism was found to be Staphylococcus aureus. This young patient
      survived and was discharged home in fair general condition.

PMID- 14710293
TI  - Isolated unilateral pleural effusion as the only manifestation of the ovarian
      hyperstimulation syndrome.
AB  - Isolated unilateral pleural effusion is uncommon presentation of ovarian hyper
      stimulation syndrome. The pathogenesis of this syndrome involved an increased
      permeability of the ovarian capillaries and of the mesothelial vessels triggered
      by the release of vasoactive substances by the ovaries under human chorionic
      gonadotropin stimulation. Early recognition of this unusual presentation of
      ovarian hyperstimulation syndrome should allow for physicians to ensure a better
      and minimally invasive management of these potentially pregnant patients.

PMID- 14710294
TI  - Benign mullerian type cyst of the uterus in a perimenopausal woman.
AB  - A perimenopausal patient presented with a history of irregular vaginal bleeding.
      Clinical examination revealed lower abdominal mass, and the pre operative
      diagnosis was an ovarian cyst. At laparotomy the ovaries and tubes were normal,
      and the cyst was anatomically attached to the uterus with a short pedicle. There
      was no obvious sign of malignancy at laparotomy. The histopathology of the cyst
      was a benign Mullerian type cyst. Bilateral tubal ligation performed at the same
      time revealed normal fallopian tubes. The patient was followed up 6 weeks and 6
      months later, and she remains symptom free. The unusual anatomical location of
      the cyst is discussed.

PMID- 14710295
TI  - Aorto carotid bypass in Takayasu's disease.

PMID- 14710296
TI  - Wandering spleen.

PMID- 14710297
TI  - The oral hygiene habits of school students in Riyadh, Saudi Arabia.

PMID- 14710298
TI  - Comparison of PCR and disc diffusion methods in detecting methicillin resistance
      among Staphylococcus species from nosocomial infections.

PMID- 14710299
TI  - Osmotic fragility and Na+-K+ ATPase activity of erythrocytes of HIV/AIDS
      patients.

PMID- 14710300
TI  - Tonsillectomy blood splash.

PMID- 14710301
TI  - Etiology of chronic diarrhea.

PMID- 14710302
TI  - Isolated agenesis of the gallbladder.

PMID- 14710303
TI  - [Intraoperative detection of ischemic brain hypoxia using oxygen tissue pressure
      microprobes].
AB  - OBJECTIVE AND IMPORTANCE: Detection of intraoperative ischemic events could lead
      to the resolution of their cause and to the prevention of the definitive
      establishment of a postoperative infarct. We want to illustrate the possibilities
      that intraoperative monitoring of oxygen tissue pressure (PtiO2) in critical
      areas during a neurosurgical vascular procedure offers, enhancing its reliability
      and immediacy in obtaining information about tissue oxygenation status as a
      marker of ischemia in the vascular territory at risk. CLINICAL PRESENTATION: We
      report the case of a 32 year-old male with a deep arteriovenous malformation
      (AVM) localised in the insular region. The patient had been previously treated
      with radiosurgery without achieving a satisfactory result. INTERVENTION: AVM
      removal was performed through a transylvian transinsular approach. PtiO2 was
      monitorised at the temporal pole (reference area) and at the posterior temporal
      region (risk area). Both probes maintained close tissue oxygenation levels until
      the last stage of the AVM resection when, during the coagulation of a supposed
      afferent vessel, a brisk fall of the oxygen tissue pressure in the posterior
      temporal region was detected. An ischemic infarct in this area was observed
      postoperatively. CONCLUSIONS: PtiO2 monitoring has a high reliability in the
      detection of intraoperative tissue hypoxia. Data obtained could lead to early
      identification of these events and, whatever possible, to resolve this situation
      preventing the definitive establishment of an ischemic infarct.

PMID- 14710304
TI  - [Intraoperative cortical mapping in the surgical resection of low-grade gliomas
      located in eloquent areas].
AB  - INTRODUCTION: Surgical selection of patients harboring low-grade gliomas based on
      radiological criteria may be insufficient due to individual variability in
      eloquent areas location and to the fact that function can be preserved within
      infiltrated brain tissue. Brain stimulation mapping safety for patients with low
      grade gliomas is evaluated, analyzing whether this technique modifies the extent
      of resection and minimizes postoperative deficits. MATERIAL AND METHODS: Twenty
      five patients with lowgrade gliomas (II/IV WHO) located in eloquent areas
      underwent tumor resection with the aid of intraoperative mapping. Patients
      underwent surgery under local or general anesthesia depending on the neurological
      function to be explored. All procedures were performed from an oncological point
      of view, trying to achieve a radical tumor resection but stopping removal
      whenever functional tissue was found within or near the lesion. RESULTS: Total or
      subtotal resection was achieved in 16 patients (64%); in five cases (20%)
      resection was partial, and in the remaining (16%) only a biopsy was obtained.
      Tumors located in the supplementary motor area (SMA) or in the operculum were
      those which could be more often totally resected. Thirteen patients (52%)
      experienced neurological worsening immediately after surgery but eight of them
      had almost completely recovered six months after the procedure. CONCLUSIONS:
      Intraoperative functional mapping can optimize extent of resection minimizing
      permanent morbidity. Functional tissue can be found within the infiltrated brain
      and this must be considered in the presurgical planning. SMA and opercular tumors
      allow radical resection with low morbidity whereas insular tumors remain a
      challenge even with the aid of this technique.

PMID- 14710305
TI  - [Pituitary apoplexy].
AB  - Pituitary apoplexy is an infrequent complication of pituitary adenomas, caused by
      hemorrhagic or ischemic infarction in the tumor, with typical clinical
      presentation: severe headache of sudden onset, visual disturbances, sleep
      tendency or comma. Along the last ten years we have treated eight patients with
      pituitary apoplexy. The diagnostic was clinically established in all of them.
      Seven cases complained of severe headache and vomiting. Eight patients reported
      visual disturbances. In one case low level of consciousness and meningeal
      irritation were the only findings. In six cases the apoplexy was the first
      pituitary adenoma manifestation. MRI and CT studies demonstrated the pituitary
      stroke in seven patients. Surgical trans-sphenoidal decompression was performed
      in seven patients, requiring urgent management in only one case. All patients
      experienced a marked visual improvement, but there was no amelioration of
      endocrine preoperative disturbances in any case. We conclude that quick
      diagnosis, early onset of hormonal therapy and urgent or delayed trans-sphenoidal
      surgery, depending on clinical manifestations, constitute the principies of the
      appropriate treatment of pituitary apoplexy.

PMID- 14710306
TI  - [Endoscopic nasal surgery in sellar tumors].
AB  - The advances in endoscopy have improved the approach to the sellar region
      throught nasal cavity. We studied 20 patients with pituitary adenomas operated on
      using an endoscope through nasal cavity with transseptal- trassphenoidal approach
      during the last two years. Average age was 45.6 years, and 75% were females. 30%
      of the patients had non functioning adenomas, 30% acromegaly, 25% Cushing's
      disease and 10% prolactinomas. No complications occurred during surgery. The more
      common complications were diabetes insipidus (two cases) and CSF leak (one case).
      Two patients needed hormonal treatment because panhypopituitarism. No patients
      developed septal perforation, nasal deformity, epistaxis, meningitis, lip
      numbness or oronasal fistula.

PMID- 14710307
TI  - [Meningioma: a model of cytogenetic evolution in tumoral initiation and
      progresion].
AB  - Meningiomas are tumors of the central nervous system with a great morphological
      heterogeneity. They are generally benign, and have the capacity to progress to a
      higher histological grade (atypical and anaplastic), which is associated with an
      increase in biological aggressivity and/or capacity to recur. Citogenetically
      this evolution is characterized by total or partial monosomy 22 in the early
      phase, continued by numerical and structural changes during tumor progression. In
      this study, we present a review of 85 cases of meningiomas: 43 benign, 28
      atypical and 14 anaplastic. We study the clinical and histopathological features,
      and their correlation with cytogenetie abnormalities present in these tumors.
      Numerical aberrations such as monosomy of chromosome 10, 14 and 18, and
      structural abnormalities such as deletions on 1p are directly associated with a
      higher agressivity of tumors. An association of aberatons on 1p and chromosome 14
      are more commonly found in atypical and anaplastic meningiomas. These facts imply
      that the presence of complex karyotypes progressively increases from grade I to
      grade III meningiomas. Furthermore, these karyotypes are common in recurrent
      tumors.

PMID- 14710308
TI  - Posterior fossa subdural hematoma mimicking intracerebellar hemorrhage.
AB  - Subdural hematomas of the posterior fossa are very rare and most cases are
      related to head injury. The influence of anticoagulation in cases of spontaneous
      development is well known. Although diagnosis is easily achieved by CT sean,
      atypical forms may lead to the wrong diagnosis of cerebellar hematoma. We present
      a case of a posterior fossa acute subdural hematoma occurring in an
      anticoagulated patient who was preoperatively misdiagnosed as an intracerebellar
      hemorrhage.

PMID- 14710309
TI  - Cervicothoracolumbar spinal epidural abscess with tetraparesis. Good recovery
      after non-surgical treatment with antibiotics and dexamethasone. Case report and
      review of the literature.
AB  - We report the conservative treatment of a spinal epidural abscess (SEA) caused by
      escherichia coli and affecting the anterior epidural space from C2 to L4 in a
      diabetic, obese patient presenting with tetraparesis. The favourable clinical
      response to the administration of dexamethasone and antibiotics is described. We
      review the literature on non-surgical treatment of SEA with special regard to the
      use of corticosteroids.

PMID- 14710310
TI  - [A case report. Right papilledema, left facial paresis].

PMID- 14710311
TI  - [The passing of time. In memory of Juan Luis Barcia Salorio].

PMID- 14710312
TI  - Intravenous leiomyomatosis.

PMID- 14710313
TI  - CT scanning for the detection of tuberculous mediastinal and hilar
      lymphadenopathy in children.
AB  - BACKGROUND: The diagnosis of primary pulmonary tuberculosis (PTB) in children
      relies heavily on the radiographic demonstration of mediastinal lymphadenopathy.
      Plain radiographs may be unreliable and CT is the current 'gold standard' for
      demonstrating this. Only two previous studies have described the CT findings of
      mediastinal adenopathy exclusively in children. OBJECTIVE: To determine the
      prevalence, distribution, characteristics and effect on the bronchial tree of
      mediastinal lymphadenopathy using modern CT techniques, in children suspected of
      PTB. MATERIALS AND METHODS: One hundred children (54 boys, 46 girls) with
      clinically suspected PTB were prospectively recruited from an overnight admission
      ward if they met the WHO criteria for suspected PTB. CT scans were evaluated by a
      panel of radiologists with regard to a predetermined set of criteria. RESULTS:
      Lymph nodes were present in 92 patients, and nodes greater than 1 cm were present
      in 46 patients. Enhancement of lymph nodes was present in 67 patients and was
      almost invariably 'ghost-like' ring enhancement. Calcification was present in
      only 9 patients. The most common location for lymphadenopathy was the subcarinal
      position ( n=90), followed by the hila ( n=85; left 74, right 72, bilateral 61),
      the anterior mediastinum ( n=79), the precarinal position ( n=64) and the right
      paratracheal position ( n=63). Multiple sites of involvement were present in 88
      patients, and a single site for lymphadenopathy (subcarinal) was present in only
      4 patients. Bronchial compression was identified in 29 patients. Most commonly,
      the left main bronchus was involved ( n=21), followed by the right main bronchus
      ( n=14) and the bronchus intermedius ( n=8), 16 right-sided compressions in
      total. CONCLUSIONS: Lymphadenopathy was common, but only 46 patients had lymph
      nodes greater than 1 cm. Enhancement characteristics of tuberculous adenopathy
      differ from that described previously. Typical enhancement was 'ghost-like'
      rather than discreet ring enhancing with a low-density centre. The site most
      frequently involved by nodes also differs from previous studies. The subcarinal
      region should be the site receiving most attention for the identification of
      lymphadenopathy, as this is most frequently involved and is also the site of the
      largest lymph-node masses. The presence of lymph-node groups at other recognised
      sites adds confidence when there is doubt, as multifocal involvement is common.
      Approximately one-quarter of patients with hilar adenopathy may have bronchial
      compression in childhood.

PMID- 14710314
TI  - Polyorchidism: imaging may denote reproductive potential of accessory testicle.
AB  - MRI in a 9-year-old boy with left testicular polyorchidism and prior right
      orchiectomy showed single epididymis-ductus deferens complex. This anatomical
      arrangement suggests the possibility of reproductive potential and alters the
      patient's management.

PMID- 14710315
TI  - Self-directed learning.

PMID- 14710316
TI  - Good readers needed.

PMID- 14710317
TI  - Self-directed learning.

PMID- 14710318
TI  - Pushing for more research.

PMID- 14710319
TI  - Effectiveness of leukotriene receptor antagonists for dysmenorrhea of
      endometriosis.

PMID- 14710320
TI  - Graduating medical students reveal that economics plays role in choice of family
      medicine.

PMID- 14710321
TI  - Macronutrients and pediatric obesity.

PMID- 14710323
TI  - Moving forward in knowledge on the process of primary care: convergence rather
      than parallelism in scholarship (hopefully).

PMID- 14710324
TI  - Primary care practice coordination versus physician continuity.
AB  - BACKGROUND AND OBJECTIVES: This study assesses the influence of primary care
      continuity--both clinician and system--on patient outcomes. We consider the
      presumed benefits of physician continuity and practice coordination within a
      multi-specialty group. METHODS: The practices of 194 family physicians and
      general internists caring for 320000 adult members of a health maintenance
      organization were evaluated using four aggregate measures of outcomes--cancer
      screening in women, diabetic management examinations, patient satisfaction
      ratings, and ambulatory costs. Physician continuity and practice coordination
      were assessed using sequential sets of multiple regression models while
      controlling for patient panel and physician characteristics. RESULTS: Physician
      continuity, defined as seeing the same designated physician during 1 year, was
      not associated with any patient outcome. Practice coordination, measured by
      shared practice, team tenure, and medical clinic size, was significantly
      associated with three of the outcomes. Both medical clinic size and shared
      practice were associated with higher rates of cancer screening and diabetic
      management examinations. Team tenure exhibited a significant positive association
      with cancer screening, diabetic management, and patient satisfaction.
      CONCLUSIONS: While physician continuity was not associated with patient outcomes,
      primary care practice structure was. Practice coordination should be assessed to
      identify mechanisms to support improved care.

PMID- 14710325
TI  - The patient-physician relationship, primary care attributes, and preventive
      services.
AB  - BACKGROUND: The importance of a sustained relationship between patients and
      physicians is a defining characteristic of family medicine. This study examined
      whether there is an association among the length of the patient-physician
      relationship, various attributes of primary care, and the delivery of clinical
      preventive services to Medicare beneficiaries. METHODS: The data source for this
      study was the 1993 Medicare Current Beneficiary Survey. Primary care attribute
      scales were developed by conducting a factor analysis of 17 survey questions.
      Three clinical preventive services were measured as outcomes: influenza
      vaccination, mammography, and an eye examination for diabetics. Path analyses
      were used to test the relationships between length of relationship, primary care
      attributes, and delivery of clinical preventive services. RESULTS: As the length
      of the relationship increased, scores on communication, accumulated knowledge of
      the patient by the physician, and trust all improved. Length of relationship and
      communication predicted accumulated knowledge of the patient by the physician,
      accumulated knowledge predicted trust, and trust predicted delivery of preventive
      services. CONCLUSIONS: Among elderly Medicare beneficiaries, the ability to
      develop a sustained relationship with a provider is related to the realization of
      other important attributes of primary care. Trust was associated with delivery of
      important clinical preventive services. Efforts should be made to protect the
      ability of patients and physicians to sustain a relationship over time.

PMID- 14710326
TI  - Managing crisis: the role of primary care for people with serious mental illness.
AB  - BACKGROUND AND OBJECTIVES: More than 30% of patients with serious mental illness
      in the United Kingdom now receive all their health care solely from primary care.
      This study explored the process of managing acute mental health crises from the
      dual perspective of patients and primary care health professionals. METHODS:
      Eighteen focus groups involving 45 patients, 39 general practitioners, and eight
      practice nurses were held between May and November 2002 in six Primary Care
      Trusts across the British West Midlands. The topic guide explored perceptions of
      gold standard care, current issues and critical incidents in receiving/providing
      care, and ideas on improving services. RESULTS: Themes relevant to the management
      of acute crisis included issues of process, such as access, advocacy,
      communication, continuity, and coordination of care; the development of more
      structured care that might reduce the need for crisis responses; and issues
      raised by the development of a more structured approach to care. CONCLUSIONS:
      Access to services is a complicated yet crucial feature of managing care in a
      crisis, with patients identifying barriers at the level of primary care and
      health professionals at the interface with secondary care. The development of
      more structured systems as a solution may generate its own ethical and pragmatic
      challenges.

PMID- 14710327
TI  - The relationship between continuity of care and trust with stage of cancer at
      diagnosis.
AB  - BACKGROUND AND OBJECTIVES: While continuity of care has been associated with an
      increased rate of cancer screening, it is unclear if continuity leads to earlier
      detection of cancer. This study examined the relationship between continuity of
      care and trust in one's physician with stage of cancer among newly diagnosed
      colorectal and breast cancer patients. METHODS: A total of 119 newly diagnosed
      cancer patients (97 breast, 22 colorectal) were surveyed in face-to-face
      interviews. The relationship between continuity of care and trust with the
      patient's primary care physicians prior to diagnosis were examined in
      relationship to the patient's stage at diagnosis via Spearman correlations and
      chi-square analyses. A stepwise logistic regression model was computed to examine
      the best predictors of stage at diagnosis. RESULTS: Half of the patients reported
      that their cancer was found through screening. Continuity of care prior to
      diagnosis was related to receiving mammography. Continuity of care was not,
      however, significantly related to earlier detection. Trust in one's primary care
      physician was related to earlier detection among both the entire sample of
      patients with colon and breast cancer and among a subsample of women with breast
      cancer. In a multivariate model, only detection through screening and trust
      predicted stage of diagnosis. CONCLUSIONS: Continuity of care is not related to
      earlier detection of cancer, while trust with a regular physician was associated
      with earlier detection of cancer.

PMID- 14710328
TI  - The challenge of promoting integration: conceptualization, implementation, and
      assessment of a pilot care delivery model for patients with type 2 diabetes.
AB  - BACKGROUND: The Cote-des-Neiges diabetes pilot project strove to conceptualize,
      implement, and assess an integrated health care system for Type 2 diabetes. Using
      a disease management and population-based approach, a multidisciplinary team
      sought to (1). organize health care in an integrative framework, (2). promote
      behavior changes in patients to foster self-care, (3). introduce tools to allow
      family physicians to modify their practices, and (4). encourage local community
      action to support patients and providers. METHODS: Information from a needs
      assessment helped guide the development of the care model, which was implemented
      over a 1-year period. A preliminary assessment was undertaken using qualitative
      methods. Data were collected through in-depth interviews, focus groups,
      participant observation, and document analysis. RESULTS: (1). Physicians and
      patients appreciated having access to a multidisciplinary team and related
      services, and personalized communication was preferred to computerized links.
      (2). Patients also perceived the benefit of individualized assessment and self
      care educational sessions allowing them to participate in their illness
      management. (3). A diabetes care flow sheet altered the management strategies of
      physicians. (4). Limited time prevented full development of networking efforts to
      promote community mobilization. CONCLUSIONS: Approaches to chronic diseases such
      as diabetes require integrative health care strategies to support patients and
      providers in their community. In spite of time constraints, patients perceived
      the value of education with increasing involvement in their illness, physicians
      reported changes in their practice, and steps were initiated to mobilize
      community resources.

PMID- 14710329
TI  - Specialist management and coordination of "out-of-domain care".
AB  - BACKGROUND AND OBJECTIVES: Fifteen percent of Medicare patients receive care only
      from specialists. This has led to the supposition that there might be a "hidden
      system of primary care," where specialists provide comprehensive care to their
      patients, including care traditionally outside their specialty domain. This study
      explores the perspectives of specialists at an academic medical center on their
      decisions to provide "out-of-domain" care and how it is coordinated. METHODS: We
      used grounded theory methodology and a constant comparative process with 13
      specialist interviews. RESULTS: Patient requests drive the provision of out-of
      domain care. Specialist comfort with this care and desire to perform it are
      involved with their decision to provide out-of-domain care. Coordination of out
      of-domain care performed by specialists can be difficult and time consuming but
      is important and is facilitated by electronic medical records. CONCLUSIONS: The
      results suggest that there is no hidden system of primary care. Coordination
      among all providers of medical care for a patient is needed to prevent medical
      errors, especially when specialists provide out-of-domain care.

PMID- 14710330
TI  - Family medicine trainees still value continuity of care.
AB  - BACKGROUND AND OBJECTIVES: Continuity of care in family medicine is under
      pressure due to an increase in part-time work, delegation of tasks, and the
      development of walk-in centers. It is uncertain to what extent newly qualified
      professionals value personal continuity. Insight into trainees' views may be
      helpful for training purposes and for improving continuity of care for patients
      in the future. We explored trainees' views on continuity for hypothetical
      scenarios and related these to personal characteristics and trainers' views.
      METHODS: We sent a questionnaire to all trainees and trainers of the eight family
      medicine training institutes in The Netherlands. RESULTS: The response rate was
      595/1048 (57%) for trainees and 478/776 (62%) for trainers. Trainees attached
      more importance to continuity than trainers. Both highly valued continuity for
      serious problems, such as discussing the future when seriously ill (99% and 97%,
      respectively) and valued it low for minor problems, such as an episode of flu
      (14% and 6%, respectively). Trainees' views were barely related to the views of
      their personal trainers and to personal characteristics such as age, gender, and
      training faculty to a minor extent only. CONCLUSIONS: The new generation of
      professionals still value continuity of care. It may remain one of the basic
      features of general practice in the future.

PMID- 14710331
TI  - What factors are associated with achieving high continuity of care?
AB  - BACKGROUND AND OBJECTIVES: Although continuity of care has been found to be
      associated with improved health outcomes in children, little is known about what
      factors predict having consistent contact with a pediatric provider. This study
      explored what patient, family, provider, and system factors are associated with
      high continuity of both total and well-child care. METHODS: This cross-sectional
      study involved 759 patients presenting to a primary care pediatric clinic.
      Patients completed surveys about demographic variables, attitudes about
      continuity of care, and family functioning, as well as provider-level
      information. Outcomes were measured with a continuity of care index that
      quantified the degree to which a patient experienced continuous care with a
      provider. RESULTS: In Tobit regression models, the variables associated with
      increased total continuity of care were continuity belief, higher family control,
      increased provider availability, and better provider rating. Associated with
      decreased total continuity of care were: number of visits, patient age, and time
      at clinic. For well-child care, the variables associated with increased
      continuity of care were continuity belief, increased provider availability,
      better provider rating, and greater reported household income. Provider
      availability was the strongest predictor of total continuity of care, and
      continuity belief was the strongest predictor of well-child continuity of care.
      CONCLUSIONS: Increased provider availability may improve overall continuity of
      care for pediatric patients.

PMID- 14710332
TI  - Continuity of care from a patient's point of view: context, process, relation.
AB  - BACKGROUND: It is easy to forget about the real human experience when faced with
      the pressure of output measurement, organizational change, and large-scale
      statistical studies. This article takes a different perspective and provides a
      glimpse into one man's life to show the many relationships that can be involved
      when someone is ill. METHODS: The information in this paper is based on
      interviews with multiple individuals involved in the care of one patient. The
      theoretical framework is narrative--it takes discourse as its material base--and
      introduces the concept of the "signifier" to organize the data. RESULTS: The
      interview results demonstrate the theoretical strength of the signifier concept
      and reveal the process and context of the work of three particular physicians and
      the nature of the relations they were able to establish with this one patient and
      his son. CONCLUSIONS: This way of conceptionalizing the process of care from the
      patient's point of view enables us to reflect on the changing nature of
      continuity of care as a core value for family physicians

PMID- 14710333
TI  - The structure of primary care: framing a big picture.

PMID- 14710334
TI  - Mathematical determination of inspiratory upper airway resistance using a
      polynomial equation.
AB  - We have previously shown that the pressure-flow relationship of the upper airway
      during nonrapid eye movement sleep can be characterized by a polynomial equation:
      F(P) = AP(3) + BP(2) + CP + D. On the basis of fluid mechanic principles, we
      hypothesized that we could objectively calculate upper airway resistance (R(UA))
      using the polynomial equation. We manually measured RUA (mR(UA)) from the first
      linear portion of a pressure-flow loop in 544 breaths from 20 subjects and
      compared the mRUA to the R(UA) calculated from the polynomial equation (cRUA).
      Bland-Altman analysis showed that the mean difference between mR(UA) and cRUA was
      0.0 cm H2O/L/s (95% CI, 0.1 to 0.1 cm H2O/L/s) with an upper limit of agreement
      of 2.0 cm H (2)O/L/s (95% CI, 1.9 to 2.1 cm H2O/L/s) and a lower limit of
      agreement -2.0 cm H2O/L/s (95% CI, -2.1 to -1.9 cm H2O/L/s). Additional Bland
      Altman analyses showed that the agreement between the two measures was excellent
      for both inspiratory flow-limited and non-flow-limited breaths. We conclude that
      R(UA) can be measured in a simple, objective, and reproducible fashion from a
      polynomial function that characterizes the upper airway pressure-flow
      relationship.

PMID- 14710335
TI  - Pulmonary function and sleep apnea.
AB  - The purpose of this study was to determine whether there is a relationship
      between pulmonary function measured during wakefulness and sleep apnea. We
      prospectively studied 1296 patients, who were free of any lung disease, referred
      to our sleep clinic for evaluation of possible sleep apnea. All patients had in
      hospital nocturnal polysomnography and pulmonary function measurements, which
      included flow-volume curve, body plethysmography, and single-breath diffusing
      capacity for carbon monoxide. The results were analyzed by comparing pulmonary
      function data between four groups of patients, grouped according to apnea
      severity as reflected by their apnea/hypopnea index: nonapneics (apnea-hypopnea
      index </= 10), mild apnea (10 < apnea-hypopnea index </= 30), moderate apnea (30
      < apnea-hypopnea index </= 50), and severe apnea (apnea-hypopnea index > 50).
      Analysis of covariance demonstrated no difference in any of the pulmonary
      function parameters between the four groups, after adjusting for age, body mass
      index, or weight as the covariate. We conclude that in nonsmoking patients
      without lung disease, sleep apnea is unrelated to pulmonary function measured
      during wakefulness.

PMID- 14710336
TI  - Symptoms of sleep breathing disorders in children are underreported by parents at
      general practice visits.
AB  - Sleep breathing disorders (SBD) in children are reportedly underdiagnosed in
      general practice. A contributory factor may be parental underreporting of
      symptoms. This possibility was examined by comparing the frequency with which
      snoring was mentioned at general practitioner visits by parents with frequency
      that snoring was reported on questionnaire evaluation immediately prior to
      consultation. We also examined the effects of age and gender on SBD symptoms.
      Parents of 626 children aged 0 to 16 years attending their general practitioner
      for sick child visits completed selected items from the Sleep Disturbance Scale
      for Children and the Obstructive Sleep Apnea Syndrome Expanded Childhood
      Questionnaire. Parents and general practitioners were also asked if snoring was
      discussed at the current consultation visit or at a prior consultation visit in
      the previous 12 months. Eighteen percent (112 of 626) of children were frequent
      snorers (more than three times per week), whereas 0.6 to 5.0% of children snored
      and had one or more additional SBD symptom suggestive of obstructive sleep apnea.
      SBD symptoms tended to peak in early to middle childhood with few gender
      differences. We found that snoring was patently underreported by parents. In the
      children with a history of frequent snoring on questionnaire evaluation and where
      the reason for the consultation visit was documented, snoring was mentioned by
      parents at the current consultation visit in only 8% (8 of 100) of cases and at a
      prior consultation visit in only 15% (15 of 100) of cases. The present findings
      support a need for increased parental education regarding the symptoms and
      clinical significance of SBD.

PMID- 14710337
TI  - Obstructive sleep apnea in a referral population in India.
AB  - There are few published studies of obstructive sleep apnea in the Asian
      subcontinent. The objectives were to describe the syndrome and evaluate the
      utility of computed tomography (CT) cephalometry in patients found to have
      obstructive sleep apnea (OSA) by polysomnography. This article reports on a
      retrospective case series in a referral population. A total of 880 patients (560
      males and 320 females) were seen in a referral center in Hyderabad, South India,
      during the last 7 years. All patients with suspected obstructive sleep apnea were
      evaluated with 16-channel polysomnogram by overnight sleep study; 600 subjects
      (68%; 480 males and 120 females) underwent evaluation with CT cephalometry. Mean
      age was 51.4 +/- 9.5 years (standard deviation). The mean apnea-hypopnea index
      (AHI) was 27.93 +/- 3.8. The majority of patients had more than 10 AHI; mean
      percentage of sleep efficiency was 80.62 +/- 15.38; mean percentage of rapid eye
      movement (REM) sleep was 13.79 +/- 7.89; mean awake arterial oxygen saturation
      (SaO2) was 90%; mean sleep SaO2 was 84% +/- 4.4%; mean Epworth Sleepiness Scale
      (ESS) score was 12.3 +/- 2.8. The tongue base area (TBA) was found to be
      significantly associated with obstructive sleep apnea (OSA), with mean TBA 1032.8
      +/- 427 mm2 compared with normal controls at 561.1 +/- 197.6 mm2 (p < 0.001).
      Mean gonion-gnathion-hyoid angle (Go-Gn-H) was 28.5 +/- 10.5 in OSA and 16 +/-
      16.7 in controls; uvula area was 452.5 +/- 145.8 mm2 in OSA and 221.4 +/- 49.85
      mm2 in controls; uvula diameter was 13.8 +/- 2.74 mm in OSA and 10.1 +/- 1.72 mm
      in controls. A total of 704 patients with OSA (80%) were found to be
      hypertensive, with daytime mean blood pressure of 160/100 +/- 8.5/4.8 mm Hg. Mean
      duration of reported hypertension was 2 years. The present study showed moderate
      to severe OSA in a majority of suspected cases referred for polysomnogram. Mild
      disease was seen in 20.45% of patients (n = 180). On CT cephalometry, the TBA
      correlated significantly with OSA; hypertension is common in patients with OSA.

PMID- 14710338
TI  - Should women with obstructive sleep apnea syndrome be screened for
      hypothyroidism?
AB  - This study was conducted to determine if there is a significant increase in
      prevalence of hypothyroidism in women with OSAS such that screening might be
      warranted. Women undergoing polysomnography (PSG) at Duke University between
      January 1, 2000 and August 21, 2001 were considered for enrollment. Those with a
      respiratory disturbance index (RDI) >/= 10 were included for further analysis.
      Demographic data and documentation of thyroid testing was obtained. Thyroid
      testing obtained within 1 year of the PSG was used for this study. Demographic
      data of the euthyroid and hypothyroid groups were compared. Prevalence of
      hypothyroidism was calculated and compared with the prevalence of hypothyroidism
      in the Framingham study. A total of 118 women had OSAS per PSG. Seventy-five
      patients had thyroid function testing within 1 year of PSG evaluation. The mean
      age, body mass index, and RDI in the euthyroid and hypothyroid groups were not
      significantly different. The prevalence of hypothyroidism was 9.3%; the
      established prevalence of hypothyroidism in women in the general population is
      5.9%. There was no statistically significant difference in the prevalence between
      these groups. The prevalence of hypothyroidism in women with OSAS is no higher
      than that seen in the general population. Screening women with symptoms of OSAS
      for hypothyroidism is unlikely to be useful.

PMID- 14710339
TI  - Improvement of facial appearance and nocturnal breathing with geniotomy (sliding
      genioplasty): report of two cases.
AB  - This article reports on two cases of nonobese female patients who presented in an
      orthodontic practice complaining of dental malocclusion and facial dysharmony.
      Because of the observed clinically and radiographically extreme mandibular
      retrognathia, they were referred for a sleep study and were found to have mild
      sleep apnea. Surgery in the form of advancement geniotomy was offered to relieve
      their retroglossal obstruction, improve their nocturnal sleep, and simultaneously
      address their facial esthetic concerns. Advancement geniotomy is useful for sleep
      apneic patients with exclusively retroglossal obstruction secondary to mandibular
      retrognathia.

PMID- 14710340
TI  - Preventative risk management for obstructive sleep apnea.

PMID- 14710343
TI  - The thymic insulin-like growth factor axis: involvement in physiology and
      disease.
AB  - A repertoire of neuroendocrine-related genes is transcribed in the non-lymphoid
      compartment of the thymus, transposing the dual physiological role of this organ
      at the molecular level in T-cell development towards the establishment of central
      T-cell self-tolerance. The "neuroendocrine self" has been defined as a series of
      antigen sequences processed from precursors predominantly expressed in the thymus
      and first encountered by differentiating T-lymphocytes in their early life. All
      the members of the insulin gene family are expressed in the thymus according to a
      precise hierarchy and cellular topography, whereby IGF-II (epithelium of the
      subcapsular cortex and medulla) exceeds IGF-I (macrophages), which in turn far
      exceeds INS (rare subsets of medullary epithelial cells). This hierarchy in the
      degree of their respective thymic expression explains why IGF-II is more
      tolerated than IGF-I, and much more so than insulin. Evidence has been found for
      significant regulatory/tolerogenic properties in the IGF-II B:11 - 25 sequence
      after analysis of the cytokine secretion profile in peripheral blood mononuclear
      cells isolated from ten DQ8+ type 1 diabetic adolescents. In the thymus, IGF
      ligands and receptors also intervene in the control of T-cell proliferation and
      differentiation. Here, we also discuss how a disturbance in the intrathymic IGF
      mediated signaling could contribute to the pathogenesis of T-cell leukemia.

PMID- 14710342
TI  - Rapid induction of IGF-IR signaling in normal and tumor tissue following
      intravenous injection of IGF-I in mice.
AB  - The detection of IGF-IR signaling in animal models has important implications for
      determining the role of this receptor in normal physiology and tumor growth.
      While many reports have correlated changes in plasma IGF-I levels in vivo with
      biological responses, few have shown that altered IGF-I levels can directly
      affect signaling within normal or tumor tissue. Here, we present new data that
      shows how the intravenous (IV) injection of IGF-I can be used to directly examine
      IGF signaling at the tissue level. Tail-vein IV injection of IGF-I into mice
      resulted in a rapid and dose-dependent activation of the IGF-I receptor and
      downstream phosphorylation of Akt and ERK1/2 in liver, kidney, and mammary gland.
      Similarly, IV IGF-I rapidly stimulated signaling in HT-29 colorectal and in MCF-7
      breast cancer xenografts. This study shows how IV IGF injection can be used to
      examine the signaling mechanisms used by IGF-IR, in both normal mammary tissue
      and during tumor growth, and may provide a model for the characterization of IGF
      inhibitors.

PMID- 14710344
TI  - The role of the GH/IGF system in pituitary tumorigenesis.
AB  - Pituitary adenomas are mostly benign tumours that originate from differentiated
      anterior pituitary cells. Altered expression of growth factors or their receptors
      could enhance clonal expansion of pituitary adenoma cells. GHRH overstimulation
      or an activating point mutation in the Gs a-subunit leads to increased GH
      secretion and tumour formation. In contrast, IGF-I suppresses basal and GHRH
      stimulated GH secretion in pituitary adenoma cells, whereas prolactin secretion
      is unaffected. Somatostatin analogues and pegvisomant, a novel growth hormone
      receptor antagonist, results in a reduction of serum IGF-I levels and clinical
      improvement in patients suffering from pituitary adenoma. Thus, this review
      focuses on the role of the growth hormone/insulin-like growth factor system in
      pituitary tumorigenesis with particular focus on the genetic alterations
      described in pituitary adenomas up to now.

PMID- 14710345
TI  - Adaptations of the IGF system during malignancy: human skeletal muscle versus the
      systemic environment.
AB  - Presented in this study are data derived from a unique cohort of patients both
      with and without cancer, for whom we not only have serum samples, allowing us to
      investigate systemic factors impacting on skeletal muscle maintenance, but also
      primary skeletal muscle cultures giving us a model to mimic the in vivo muscle
      milieu. Possible local effects of autocrine/paracrine and endocrine IGF system
      components impacting on myoblast growth and differentiation could therefore be
      assessed. We report for the first time that the decrease in myoblast stem cell
      numbers seen with normal aging is lost in cancer patients. We further report that
      serum IGF-I, IGF-II and IGFBP-3 all show positive correlations with myoblast
      retrieval in control patients, but that with the exception of IGFBP-3 these
      correlations are lost in malignancy. Indeed IGF-II switches to a negative
      correlation with myotube formation in malignancy. Furthermore we provide initial
      evidence to suggest that there is an apparent altered regulation of local IGFBP-3
      production during malignancy which may enable satellite cell proliferation, stem
      cell infiltration or both. Finally we show the importance of investigations not
      only monitoring the systemic impact of serum factors on skeletal muscle responses
      but also critically assessing the role that locally produced muscle IGFBP-3 may
      have on the systemic environment.

PMID- 14710346
TI  - Impact of IGF-I/IGF-IR circuit on the angiogenetic properties of Ewing's sarcoma
      cells.
AB  - The insulin-like growth factor receptor I (IGF-I)-mediated circuit is a major
      autocrine loop for Ewing's sarcoma (ES) cells, and plays a role the pathogenesis
      and malignancy of this tumor. IGF-I receptor (IGF-IR) has emerged as a good
      therapeutic site for ES patients. In this study, we analyzed the impact of
      strategies targeting the IGF-IR on the regulation of VEGFs, which are of
      fundamental importance in angiogenesis, and TGFbeta, CTGF and Cyr61, which are
      factors primarily involved in skeletal growth control and angiogenesis. IGF-I
      increases expression of VEGF-A, TGFbeta, CTGF and Cyr61 mRNA. However, only the
      modulation of VEGF-A expression appears to be mediated by IGF-IR. Functional
      assays on endothelial cells indicate a strict correlation between survival and
      proliferation of HUVECs and VEGF-A levels, confirming a major role for this
      factor in angiogenesis. Blockage of IGF-IR functions by neutralizing antibody or
      antisense strategies significantly reduced the expression and secretion of VEGF-A
      by ES cells, and supernatants of treated cells were unable to sustain the
      survival and proliferation of HUVECs. Analysis of the signaling mechanisms
      involved in constitutive or IGF-induced expression and secretion of VEGF-A
      indicated that PI3-K and MAPK signaling pathways are both required for VEGF
      expression and production in ES cells. Selective inhibitors LY294002 or PD98059
      were highly effective in reducing the ability of ES cells to produce VEGF-A and
      stimulate survival and proliferation of HUVECs. Taken together, these findings
      add a new activity to the IGF-I repertoire in ES and highlight how disruption of
      IGF-IR functions may constitute an effective tool for the control of
      neovascularization in this tumor.

PMID- 14710347
TI  - The role of the IGF axis in hepatocarcinogenesis.
AB  - Primary hepatocellular carcinoma (HCC) is one of the most common forms of
      malignant cancer with the fourth highest mortality rate worldwide. Major risk
      factors for the development of HCC include chronic infections with the hepatitis
      B or C virus, alcohol consumption, exposure to dietary aflatoxin B1, hereditary
      liver disease or liver cirrhosis of any etiology. Recent studies have discovered
      changes in the insulin-like growth factor (IGF) axis that affect the molecular
      pathogenesis of HCC, including the autocrine production of IGFs, IGF binding
      proteins (IGFBPs), IGFBP proteases, and IGF receptor expression. Characteristic
      alterations detected in HCC and hepatoma cell lines comprise the overexpression
      of IGF-II and the IGF-I receptor emerging as critical events in malignant
      transformation and growth of tumors. Simultaneous reduction of IGFBP expression
      and the increase in proteolytic cleavage of IGFBPs result in an excess of
      bioactive IGFs. Finally, defective functions of the IGF-II/mannose 6-phosphate
      receptor involved in degradation of IGF II, the activation of the growth
      inhibitor TGF-beta1, and the lysosomal targeting of cathepsin proteases capable
      to degrade extracellular matrix proteins may contribute to the development of
      HCC.

PMID- 14710348
TI  - Nutrition, insulin, insulin-like growth factors and cancer.
AB  - The incidence of colon, pancreatic, and kidney cancers, as well as aggressive
      prostate cancer in men, and breast and endometrial cancer in women is invariably
      high in Western countries. Nutritional and related factors have been typically
      implicated. This review presents a model integrating nutrition, insulin and IGF-1
      physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1)
      insulin and the IGF-1 axis function in an integrated fashion to promote cell
      growth and survival; (2) chronic exposure to these growth properties enhances
      carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer
      risk. The model presented here summarizes the data that chronic exposure to high
      levels of insulin and IGF-1 may mediate many of the risk factors for some cancers
      that are high in Western populations. This hypothesis may help explain some of
      the epidemiologic patterns observed for these cancers, both from a cross-national
      perspective and within populations. Of particular importance is that some of
      relevant factors are modifiable through nutritional and lifestyle interventions.
      Out of a variety of perspectives presented, nutritional manipulation through the
      insulin pathway may be more feasible than attempting to influence total IGF-1
      concentrations, which are determined largely by growth hormone. Further study is
      required to test these conclusions.

PMID- 14710349
TI  - Caloric restriction and insulin-like growth factors in aging and cancer.
AB  - This review examines the influence of a reduction in caloric intake on cancer and
      longevity. Data indicating that rodents subjected to caloric restriction display
      lower tumor incidence, reduced susceptibility to carcinogens and extended
      lifespan is analyzed. The potential role of the growth hormone/insulin-like
      growth factor type 1 (IGF-I) axis in this effect is discussed as is the evidence
      that a reduction in growth hormone and/or IGF-I leads to a reduction in
      spontaneous tumors and susceptibility to carcinogens.

PMID- 14710350
TI  - Acromegaly and colorectal cancer: a comprehensive review of epidemiology,
      biological mechanisms, and clinical implications.
AB  - Acromegaly is an endocrine disorder characterised by sustained hypersecretion of
      growth hormone (GH) with concomitant elevation of insulin-like growth factor
      (IGF)-I, and is associated with malignancy and premature mortality from
      cardiovascular and respiratory diseases. In particular, there may be an increased
      risk of colorectal neoplasia, but the exact extent of this is contentious.
      Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are
      misleading, but population-based studies on colorectal cancer risk are more
      consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI:
      1.32, 3.14). Possible mechanisms underlying this increased risk include direct
      actions as a consequence of elevated levels of circulating GH and IGF-I and/or
      other perturbations within the IGF system. Other possible mechanisms include
      altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared
      genetic susceptibility and increased bowel length. However, most explanations
      only offer indirect evidence, and the expectation of acromegaly as a natural
      model of colorectal carcinogenesis has not materialised. From a clinical
      perspective, it seems reasonable to consider a once-only colonoscopic screening
      at approximately age 55 years, but potential risks and benefits should be
      balanced.

PMID- 14710351
TI  - Epidemiology and biology of insulin-like growth factor binding protein-3 (IGFBP
      3) as an anti-cancer molecule.
AB  - The Insulin-like Growth Factor (IGF) signaling system plays a central role in
      cellular growth, differentiation and proliferation. IGFBP-3 is the most abundant
      IGF binding protein in human serum and has been shown to be a growth inhibitory,
      apoptosis-inducing molecule, capable of acting via IGF-dependent and IGF
      independent mechanisms. Over the last decade, several clinical studies have
      proposed that individuals with IGFBP-3 levels in the upper range of normal may
      have a decreased risk for certain common cancers. This includes evidence of a
      protective effect against breast cancer, prostate cancer, colorectal cancer, and
      lung cancer. In addition, a series of in vitro studies and animal experiments
      point towards an important role for IGFBP-3 in the regulation of cell growth and
      apoptosis. In this brief review, we discuss the biological role of IGFBP-3 and
      summarize the epidemiological and experimental evidence suggesting a role for
      IGFBP-3 as an anti-cancer molecule.

PMID- 14710352
TI  - Subcellular localization of IRS-1 in cell proliferation and differentiation.
AB  - The type 1 insulin-like growth factor receptor (IGF-IR) and its docking protein,
      insulin receptor substrate-1 (IRS-1), play important roles in cell
      transformation, cell differentiation and aging. IRS-1 and other IRS proteins can,
      under certain conditions, localize to the nuclei of cells, where they undergo
      interactions with nuclear and nucleolar proteins. In this study, we confirm and
      extend these observations, demonstrating that IRS-1 is preferentially nuclear in
      growing cells. Differentiation and inhibition of ribosomal RNA synthesis cause
      subcellular redistribution of IRS-1 and other nuclear proteins to the cytoplasm.

PMID- 14710353
TI  - The insulin-like growth factor axis in cell cycle progression.
AB  - Emerging evidence suggests that members of the Insulin-like Growth Factors (IGFs)
      family, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding
      proteins (IGFBPs) play a central role in the development and progression of
      cancer. Cancer cells exhibit an increased and deregulated proliferative activity.
      Abnormalities in many positive and negative modulators of the cell cycle are also
      frequent in many cancer types. Recent advances in the understanding of cell-cycle
      control mechanisms have been applied to outline the molecular mechanism through
      which IGFs regulate cell cycle progression. In this review, we will provide a
      brief overview of the role of the IGF system as a regulator of some components of
      the cell cycle.

PMID- 14710354
TI  - Activation of pro-apoptotic p38-MAPK pathway in the prostate cancer cell line M12
      expressing a truncated IGF-IR.
AB  - The type I insulin-like growth factor receptor (IGF-IR) plays a critical role in
      signaling survival and proliferation in many cell types. Activation of IGF-IR by
      its ligands promotes cell proliferation via mitogen-activated protein kinase
      (MAPK) cascade and cell survival via phosphoinositide 3-kinase (PI3K) cascade.
      The IGF-IR emerges as a powerful growth factor for many tumor cells. A truncated
      IGF-IR 486/STOP, described as a dominant negative IGF-IR mutant, was shown to
      induce apoptosis and inhibit tumor growth in vivo while endogenous IGF-IR was
      activated. To investigate the mechanism(s) of the action of 486/STOP, we have
      introduced 486/STOP into the prostate tumor model cell line M12 and its
      derivative M12lisn that expresses high levels of wild type IGF-IR. We have found
      that 486/STOP induces apoptosis in M12 and M12lisn cells in culture and that
      486/STOP acts through activation of the pro-apoptotic p38-MAPK without
      interfering with wild type IGF-IR activation. In addition, our results have
      indicated that 486/STOP induced activation of p38-MAPK increases through
      activation of endogenous IGF-IR. These data suggest that activation of the IGF-IR
      by 486/STOP can selectively enhance the previously reported IGF-IR pro-apoptotic
      signaling pathways.

PMID- 14710355
TI  - Functional and physical interactions between BRCA1 and p53 in transcriptional
      regulation of the IGF-IR gene.
AB  - The insulin-like growth factor-I receptor (IGF-IR) mediates the biological
      actions of the IGFs, and is critical for normal mammary gland development as well
      as for malignant transformation. Transcription of the IGF-IR gene is under
      inhibitory control by a number of transcription factors with tumor suppressor
      activity, including BRCA1 and p53. To assess the potential functional
      interactions between BRCA1 and p53 in transcriptional control of the IGF-IR gene,
      co-transfections were performed on MCF-7 breast cancer cells using an IGF-IR
      promoter luciferase reporter construct together with expression vectors encoding
      BRCA1 and wild-type and mutant p53. Similar experiments were performed in the
      colorectal cancer cell line HCT116 (+/+), which expresses a wild-type p53 gene,
      and its HCT116 (-/-) derivative, which lacks p53. BRCA1 was able to suppress IGF
      IR promoter activity both in the absence and presence of p53. However, BRCA1 had
      no effect in mutant p53-expressing cells. Co-immunoprecipitation experiments
      showed that BRCA1 and p53 physically interact. In summary, our data suggest that
      the transcriptional activity of BRCA1 depends on the cellular status of p53.
      Inability of mutant tumor suppressors to repress IGF-IR gene expression may
      result in increased IGF-IR levels and IGF binding, leading to a reduction in
      apoptosis and enhanced survival capacity of malignant cells.

PMID- 14710356
TI  - Insulin-like growth factor-I suppresses degradation of the pro-survival
      transcription factor myocyte enhancer factor 2D (MEF2D) during neuronal
      apoptosis.
AB  - Cultured rat cerebellar granule neurons (CGNs) require depolarization-mediated
      calcium influx for survival. Calcium regulates the activity of the pro-survival
      transcription factor, myocyte enhancer factor 2D (MEF2D). MEF2D is
      hyperphosphorylated and degraded in CGNs undergoing apoptosis induced by lowering
      the extracellular potassium concentration from 25 mM to 5 mM. Since insulin-like
      growth factor-I (IGF-I) is known to protect CGNs from apoptotic cell death, we
      investigated the effects of IGF-I on MEF2D processing during apoptosis. IGF-I
      administered during the apoptotic insult did not prevent the hyperphosphorylation
      of MEF2D and consequential loss of DNA binding. However, IGF-I significantly
      blocked the degradation of MEF2D. Furthermore, IGF-I had no effect on the initial
      loss of MEF2 transcriptional activity following hyperphosphorylation, but the
      recovery of MEF2 activity following restoration of intracellular calcium was
      significantly increased by IGF-I. We conclude that IGF-I blocks the degradation
      of MEF2D and enhances recovery of MEF2 activity by protecting MEF2D from caspase
      dependent cleavage during apoptosis. These results suggest that IGF-I can prolong
      the time of commitment to irreversible cell death and enhance the recovery of
      neurons subjected to an acute apoptotic stimulus by preserving the activity of
      the pro-survival factor MEF2D.

PMID- 14710357
TI  - Regulation of IGF-I receptor signaling in tumor cells.
AB  - Signals from the IGF-IR and other members of the IR family contribute to the
      growth, survival, adhesion, and motility of tumor cells. These signals are
      initiated through recruitment of adapter proteins including the IRS family and
      Shc proteins, and are mediated through the PI3-kinase, mitogen activated protein
      (MAP) kinase and stress-activated protein kinase (SAPK) pathways. Regulation of
      signaling responses from the IGF-IR involves the actions of regulatory adapter
      proteins including RACK1 and Grb10 that recruit or sequester cytoplasmic
      proteins, and the actions of phosphatases including tyrosine PTP-1B, PTEN, and
      PP2A. This review focuses on the signaling pathways that are activated by the IGF
      IR in tumor cells, the mechanisms of regulation of these pathways by adapter
      proteins and phosphatases, and how modulation of IGF-IR signaling could
      contribute to cancer progression.

PMID- 14710358
TI  - The insulin receptor isoform exon 11- (IR-A) in cancer and other diseases: a
      review.
AB  - The insulin receptor plays a vital role in mediating the actions of insulin.
      These include metabolic and mitogenic effects. This review will focus on the role
      of the insulin receptor isoforms in normal development and the pathogenesis of
      certain cancers and type 2 diabetes. There are two insulin receptor isoforms
      arising from the alternative splicing of exon 11 resulting in either the exon 11+
      (IR-B) isoform (including 12 amino acids encoded by exon 11) or the exon 11- (IR
      A) isoform. The isoforms have different affinities for insulin, IGF-II and IGF-I
      with the exon 11- isoform binding both insulin and IGF-II with high affinities.
      Interestingly, differential expression of the insulin receptor isoforms has been
      demonstrated in disease. Several cancer cell types that also overexpress IGF-II
      preferentially express the exon 11- isoform. Activation of the exon 11- insulin
      receptor by IGF-II and insulin results in mitogenic effects and a potentiation of
      the cancer phenotype. Also hyperinsulinemia has been associated with increased
      risk of cancer. Differential expression of the insulin receptor isoforms has also
      been demonstrated in type 2 diabetes although there is some discrepancy in the
      literature as to which isoform is expressed.

PMID- 14710359
TI  - Insulin-like growth factor I (IGF-I) stimulates proliferation but also increases
      caspase-3 activity, Annexin-V binding, and DNA-fragmentation in human MG63
      osteosarcoma cells: co-activation of pro- and anti-apoptotic pathways by IGF-I.
AB  - Insulin-like growth factor-I (IGF-I) was found to promote proliferation, cell
      survival, and inhibition of apoptosis. But in some instances, IGF-I was found to
      mildly induce apoptosis, i. e. Fas-mediated apoptosis in human MG63 osteosarcoma
      cells. In the present study, we intended to further investigate IGF-I dependent
      pathways leading either to proliferation and cell survival or to cell death. MG63
      osteosarcoma cells were treated with serum free medium alone or in combination
      with IGF-I, a neutralizing antibody against the human IGF-I receptor (alphaIR-3)
      or non-immune control IgG (1) for two to six days. We investigated cell survival
      (cell count), proliferation (CD71-FACS), apoptosis (Annexin-V-FACS, Caspase-3
      activity, PCD) and anti-apoptosis (112-Ser Bad phosphorylation), and regulation
      of IGF-I receptor surface expression (IGF-I receptor-FACS). We found that IGF-I
      treatment (48 h) stimulated cell growth and proliferation, but also mildly
      induced apoptosis. IGF-I activated specific apoptotic pathways (Caspase-3
      activation, Annexin-V binding and DNA degradation), as well as anti-apoptotic
      signals (Bad phosphorylation at serine 112). alphaIR-3 blocked cell
      proliferation, strongly induced apoptosis, and inhibited Bad-phosphorylation.
      Thus, IGF-I treatment overall resulted in increased tumour cell mass, despite a
      detectable stimulation of apoptosis; in other words proliferation exceeded cell
      death. If IGF-I was first added on day 0, 2, or 4 of serum free culture, we found
      decreasing IGF-I specific effects on proliferation and apoptosis. In parallel, we
      found a down-regulation of IGF-I receptors (FACS) by serum withdrawal, which was
      partly reversed if IGF-I was added. Therefore receptor number might have an
      impact on IGF-I function in MG63 cells. In conclusion, co-activation of apoptosis
      and proliferation by IGF-I might result in higher cell turnover in MG63
      osteosarcoma cells. Furthermore, in sarcomas or carcinomas showing clinical
      association to IGF-I levels and malignancy, IGF-I dependent apoptosis and
      proliferation could be a significant mechanism of malignant tumour growth.

PMID- 14710360
TI  - Expression of the insulin-like growth factor-I receptor in primary breast cancer
      and lymph node metastases: correlations with estrogen receptors alpha and beta.
AB  - Numerous laboratory studies and some epidemiological data have suggested the
      involvement of the insulin-like growth factor-I receptor (IGF-IR) in breast
      cancer development and progression. However, data on IGF-IR expression in human
      tissues, including breast cancer sections, are limited and often inconsistent. We
      therefore examined by immunohistochemistry the expression of IGF-IR in primary
      tumors and breast cancer metastases to lymph nodes, and correlated IGF-IR
      positivity with estrogen receptor (ER) status and selected clinicopathological
      features. We found that 1) IGF-IR was expressed in primary tumors as well as in
      lymph node metastases, but the expression in primary tumors was more frequent (56
      % vs. 44.4 %); 2) IGF-IR expression in primary tumors was associated with
      negative node status (p < 0.033); 3) in node-negative primary tumors, IGF-IR
      positively correlated with ERbeta (p < 0.008; r = 0.538), but not with ERalpha,
      tumor size or grade; 4) both IGF-IR-positive and IGF-IR-negative primary tumors
      were found to produce IGF-IR-positive as well as IGF-IR-negative metastases; 5)
      in metastases, IGF-IR expression did not associate with ERalpha, ERbeta or any of
      the studied pathobiological markers. The results suggest that IGF-IR could become
      a viable pharmaceutical target in breast cancer therapy, but such therapy should
      be based on IGF-IR assessment in primary tumor and metastasis in each potential
      patient.

PMID- 14710361
TI  - The role of the IGF-I receptor in the regulation of matrix metalloproteinases,
      tumor invasion and metastasis.
AB  - The breakdown of the extracellular matrix (ECM) by proteinases is an essential
      step in the process of cancer invasion and metastasis. Malignant progression is
      frequently associated with upregulated production and/or activity of one or
      several ECM degrading proteinases. Prominent among them are the matrix
      metalloproteinases (MMPs). The MMPs constitute a family of structurally related,
      zinc-dependent endopeptidases collectively capable of degrading essentially all
      the components of the extracellular matrix. At present, 23 members of the human
      MMP gene family are known. The increased expression and/or activity of one or
      more members of this family have been documented in essentially all human
      malignancies and some have been implicated in the process of angiogenesis.
      Prominent among those are MMP-2 and MT1-MMP, two metalloproteinases that form a
      cell membrane-associated complex leading to MMP-2 activation and ECM proteolysis.
      Here, we review our data that identified the type 1 insulin-like growth factor
      receptor (IGF-IR) as a regulator of tumor invasion and the synthesis of MT1-MMP
      and MMP-2 and report on the signal transduction pathways that mediate this
      regulation. These findings are discussed in the context of a broader review of
      the role of the IGF-IR/IGF axis in the regulation of tumor invasion and
      metastasis.

PMID- 14710362
TI  - Modulation of the actions of IGFs by IGFBP-5 in the mammary gland.
AB  - IGFBP-5 has been associated with cell death in a number of systems; recently, the
      first evidence that it is involved in apoptosis of the mammary gland has been
      provided by studies, both in vivo and in vitro, involving the addition of
      exogenous IGFBP-5 and from a transgenic mouse expressing IGFBP-5 on a mammary
      specific promoter. These studies have indicated that the effects are mediated in
      part by inhibition of IGF-signalling and involving members of the Bcl-2 family,
      but a role for IGF-independent effects cannot be ruled out. These IGF-independent
      effects involve potential interactions with components of the extracellular
      matrix involved in tissue remodelling such as components of the plasminogen
      system. In addition, intracellular events involving nuclear localisation of IGFBP
      5 have been shown to have potential to inhibit cell proliferation. IGFBP-5 binds
      to a considerable number of molecules in the extracellular matrix, but the
      specific roles of these interactions in modulating its biological effects are
      poorly understood. The development of IGFBP-5 mutants, with differential binding
      characteristics, will aid in elucidating the precise roles of IGFBP-5 and
      potentially offer new therapeutic approaches based on IGF-independent effects in
      addition to its classical role of modulating IGF actions.

PMID- 14710363
TI  - Increased activity of catalase in tumor cells overexpressing IGFBP-2.
AB  - Elevated levels of IGFBP-2 are found in serum and tissues under various stressful
      conditions and in many malignancies. In previous studies, we have shown that
      overexpression of IGFBP-2 results in increased tumorigenic potential in Y-1 mouse
      adrenocortical tumor cells, and that these effects are presumably mediated
      through IGF-independent mechanisms. Here, we show that highly proliferative IGFBP
      2-overexpressing Y-1 cells, but not control Y-1 cells, grow to very high cell
      densities. In order to evaluate whether the increased cell densities in IGFBP-2
      transfected Y-1 cells were accompanied by alterations in the oxidative stress
      system, we analyzed the effect of IGFBP-2 overexpression on the activity of
      various antioxidative enzymes in two malignant cell lines. Among the tested
      antioxidative enzymes (catalase, superoxide-dismutase, glutathione peroxidase,
      glutathione S-transferase), only catalase enzyme activity was significantly
      higher in IGFBP-2-transfected Y-1 mouse adrenocortical tumor cells and in IGFBP-2
      transfected human colon tumor cells (Caco-2) compared to control-transfected Y-1
      and Caco-2 cells and non-tumor 293 human epithelial cells. However,
      overexpression of catalase in malignant cells did not result in increased
      resistance to oxidative stress as measured by cell viability and protein
      oxidation after treatment of the cells with hydrogen peroxide. This might be due
      to an upregulation of the GST enzyme activity after treatment with H (2)O (2)
      that we observed selectively in the control-transfected Y-1 cells and which might
      compensate for the higher catalase activity in the IGFBP-2 overexpressing cells.
      In summary, we found a strong and selective upregulation of the catalase activity
      in IGFBP-2 overexpressing malignant Y-1 and Caco-2 cell lines that might
      contribute to the highly malignant phenotype of IGFBP-2 overexpressing tumors
      through as yet unknown mechanisms.

PMID- 14710364
TI  - Insulin-like growth factor binding protein-6 and CCI-779, an ester analogue of
      rapamycin, additively inhibit rhabdomyosarcoma growth.
AB  - Rhabdomyosarcomas secrete high levels of insulin-like growth factor-II,
      suggesting this autocrine growth factor plays a major role in the unregulated
      growth of this childhood cancer. Treatment of Rh30 rhabdomyosarcoma cells with
      insulin-like growth factor binding protein-6 (IGFBP-6; 1000 ng/ml), which binds
      insulin-like growth factor-II with high affinity, inhibited growth in vitro (p <
      0.001). Co-incubation of cells with rapamycin (1.56 ng/ml), an inhibitor of p70
      S6 kinase, and IGFBP-6 (200 ng/ml) resulted in a significant reduction in Rh30
      cell number compared to rapamycin or IGFBP-6 alone (p < 0.05 for both). Co
      treatment of Rh30 cells with CCI-779 (5 and 50 ng/ml), an ester analogue of
      rapamycin, and IGFBP-6 (200 or 1000 ng/ml) also inhibited growth in vitro
      relative to CCI-779 alone (p < 0.01 and p < 0.001, respectively). In a nude mouse
      model, xenografts of Rh30 cells transfected with a recombinant vector encoding
      IGFBP-6 (phBP6-E3) showed delayed growth relative to vector control xenografts
      (27 days vs. 19 days to reach an average tumour volume of 0.5 cm (3); p < 0.001).
      Treatment with CCI-779 (10 mg/kg) of mice inoculated with vector control
      xenografts, also delayed growth (to 31 days; p = 0.0055) relative to untreated
      mice with vector control xenografts. Co-treatment with CCI-779 (10 mg/kg) reduced
      phBP6-E3 transfected xenograft growth even further (to 45 days) compared to
      vector control xenografts (p < 0.001, day 33). CCI-779 thus acts additively with
      IGFBP-6 to reduce rhabdomyosarcoma growth both in vitro and in vivo.

PMID- 14710365
TI  - Actions of IGFBP on epithelial cancer cells: potential for new therapeutic
      targets.

PMID- 14710366
TI  - Combined effects of tamoxifen and a chimeric humanized single chain antibody
      against the type I IGF receptor on breast tumor growth in vivo.
AB  - Proliferative and anti-apoptotic actions of IGFs are mediated by the IGF-I
      receptor (IGF-IR), to which both IGF-I and -II bind with high affinity. We
      previously reported that alphaIGF-IR scFv-Fc (scFv-Fc) consisting of the alphaIGF
      IR scFv and human IgG (1) Fc domain retained general characteristics of the
      parental 1H7 monoclonal antibody, and significantly suppressed MCF-7 tumor
      growth. We proposed IGF-IR down-regulation as a possible mechanism for inhibition
      of MCF-7 tumor growth. To further determine the therapeutic potentials of this
      approach, in vivo effects of this antibody on breast tumor growth were evaluated
      in the absence or presence of tamoxifen (Tam) using a T61 human breast tumor
      model. T61 xenograft growth in athymic mice was compared under five conditions,
      PBS, scFv-Fc, Tam, scFv-Fc+Tam, and control antibody. While treatment with PBS
      and control antibody did not affect T61 tumor growth, scFv-Fc, Tam, and scFv
      Fc+Tam treatments significantly suppressed the tumor growth during the first two
      weeks of treatment. Although the growth inhibitory effect of scFv-Fc during the
      first two weeks was significant, the tumor grew as rapidly as PBS-treated tumors
      thereafter. This rapid tumor growth was suppressed when scFv-Fc was combined with
      Tam. Throughout four weeks, the combined Tam+scFv-Fc treatment was more effective
      in inhibiting the T61 tumor growth than scFv-Fc or Tam treatment alone. scFv-Fc
      treatment down-regulated IGF-IR which appears to contribute to tumor growth
      inhibition. This study provides evidence that simultaneous targeting of IGF-IR
      and the estrogen receptor may enhance the therapeutic effect.

PMID- 14710367
TI  - Development of molecular agents for IGF receptor targeting.
AB  - The type 1 insulin-like growth factor receptor (IGF1R) is a promising anticancer
      treatment target, being frequently overexpressed by tumours, and mediating
      proliferation, motility and apoptosis protection. Design of specific kinase
      inhibitors is problematic because of homology between the IGF1R and insulin
      receptor. This obstacle can be circumvented using sequence-specific molecular
      agents including antisense, triplex and ribozymes. Recent studies indicate that
      profound sequence-specific IGF1R gene silencing can be induced by small
      interfering RNAs that mediate RNA interference in mammalian cells. IGF1R
      downregulation blocks tumour growth and metastasis, and enhances sensitivity to
      cytotoxic drugs and irradiation. In murine melanoma cells, radiosensitisation is
      associated with impaired activation of Atm, which is required for initiation of
      cell cycle checkpoints and DNA repair pathways after double-strand DNA breaks.
      Furthermore, tumour cells killed in vivo following IGF1R downregulation can
      provoke an immune response, protecting against tumour rechallenge. After years of
      studying the role of the IGF system in tumour biology, novel agents for IGF1R
      targeting will soon be available for clinical testing. This review summarises the
      development of molecular agents, and considers factors that will influence
      clinical activity, including the requirement of established tumours for IGF
      signalling, and the efficacy and toxicity of IGF1R inhibitors.

PMID- 14710368
TI  - Inhibition of the biologic response to insulin-like growth factor I in MCF-7
      breast cancer cells by a new monoclonal antibody to the insulin-like growth
      factor-I receptor. The importance of receptor down-regulation.
AB  - We developed a mouse monoclonal antibody (4G11) against insulin-like growth
      factor I receptor by immunizing mice with mouse embryo fibroblasts overexpressing
      the human insulin-like growth factor-I receptor. Not only did the 4G11 antibody
      inhibit the binding of [ (125)I]insulin-like growth factor-I to the fibroblast
      receptor, but 4G11 antibody also potently down-regulated the insulin-like growth
      factor-I receptor. 4G11 Fab fragment inhibited ligand binding, but did not down
      regulate the receptor, suggesting that receptor aggregation is required for down
      regulation. 4G11 antibody also down-regulated the receptor in MCF-7 breast cancer
      cells, a panel of colon cancer cells and MG-63 osteosarcoma cells. Receptor
      recovery in MCF-7 cells after down-regulation by 4G11 antibody was slow,
      requiring 32 - 48 h for full recovery. Receptor down-regulation in MCF-7 cells by
      4G11 antibody was confirmed by FACS analysis of intact and permeabilized cells.
      In contrast to 4G11 antibody, insulin-like growth factor-I did not down-regulate
      the receptor in MCF-7 cells. Down-regulation of the receptor by 4G11 antibody in
      MCF-7 cells resulted in inhibition of Akt and MAPK activation by insulin-like
      growth factor-I. We conclude that the ability of a monoclonal antibody to down
      regulate the receptor may be an important antibody property in targeting the
      insulin-like growth factor-I receptor for the treatment of certain cancers.

PMID- 14710369
TI  - The insulin-like growth factors and insulin-signalling systems: an appealing
      target for breast cancer therapy?
AB  - There is compelling evidence from epidemiological studies in humans, as well as
      in vitro and in vivo experimental observations including transgenic animal
      models, for a role of the IGF/insulin signalling system in cancer tumourigenesis.
      In this review focused on breast cancer, we review the experimental evidence,
      discuss the cellular and molecular mechanisms of tumourigenicity by the IGFs and
      insulin and various possible therapeutic strategies based on the mechanisms
      discussed.

PMID- 14710370
TI  - Bone microdamage and cell apoptosis.
AB  - Accumulation of microdamage in bone leads to the reduced strength of our
      skeleton. In health, bone adapts to the prevailing mechanical needs of the
      organism and is also capable of self-repair, sensing, removing and replacing
      damaged or mechanically insufficient volumes of bone. In disease and old age
      these characteristics are reduced. In order to undertake both of the processes of
      functional adaptation and repair the bone resorbing and forming cells must be
      very accurately targeted to areas of physiological need. The mechanism by which
      cells are precisely targeted to areas requiring repair is both clinically
      relevant and poorly understood. The osteocyte has been assumed to play a role in
      sensing damage and signaling for its removal, due largely to its abundance
      throughout the mineralized bone matrix. However, until recently there has been
      little evidence that osteocyte function is modified in the vicinity of the
      microdamage. Here I outline the possibility that the targeted removal of bone
      containing microcracks might involve signals derived from the apoptotic death of
      the osteocyte. I shall discuss data that support or refute this view and will
      consider the possible molecular mechanisms by which controlled cell death might
      contribute to the signals for repair in the light of work involving cells in bone
      and other tissue systems.

PMID- 14710374
TI  - Hypothermic cardiopulmonary bypass and circulatory arrest in the management of
      extensive thoracic and thoracoabdominal aortic aneurysms.
AB  - Hypothermic cardiopulmonary bypass, usually in combination with an interval of
      circulatory arrest, was used for the treatment of 211 patients with extensive
      thoracic or thoracoabdominal aortic disease during a 17-year interval. Profound
      hypothermia, distal perfusion, and intravenous methylprednisolone and thiopental
      were used for neuroprotection. No other technique or other adjunctive agents were
      used. The 30-day mortality rate was 7.1% (15 patients). It was 40% (8 of 20) for
      patients undergoing emergent operations for aortic rupture or acute dissection
      and 3.7% (7 of 191) for all other patients (P<0.001). Paraplegia occurred in 5
      and paraparesis in 1 of the 205 operative survivors whose lower limb function
      could be assessed postoperatively (2.9%). Of the 121 survivors with
      thoracoabdominal aortic disease, paraplegia occurred in 1 of 38 patients with
      Crawford type I disease (2.6%), 2 of 49 with type II (4.1%), and 2 of 34 with
      type III (5.9%). Paralysis developed in 1 (1.7%) of the 58 patients who underwent
      aortic dissection. Renal dialysis was required in 6 (2.9%) of the 205 operative
      survivors, prolonged inotropic support (>48 hours) in 23 (11%), reoperation for
      bleeding in 10 (5%), mechanical ventilation (>48 hours) in 50 (24%), and
      tracheostomy in 21 (10%). Four (1.9%) patients sustained a stroke. Hypothermic
      cardiopulmonary bypass provides safe and substantial protection against
      paralysis, and renal, cardiac, and visceral organ system failure that equals or
      exceeds that of other currently used techniques but without the need for other
      adjuncts.

PMID- 14710373
TI  - The use of left heart bypass in the repair of thoracoabdominal aortic aneurysms:
      current techniques and results.
AB  - The surgical repair of thoracoabdominal aortic aneurysms (TAAA) remains
      challenging. The prevention of spinal cord ischemic complications requires a
      multidisciplinary approach. The protective effect of left heart bypass (LHB),
      particularly regarding spinal cord ischemia, during the repair of extensive TAAA
      is evaluated here. Data from 1,250 consecutive patients who underwent the repair
      of extent I or extent II TAAA over a 16-year period was prospectively entered
      into a database. LHB was used in 666 (53.3%) patients. This group was
      retrospectively compared with 584 (46.7%) patients who had undergone surgery
      without the use of LHB. A total of 1,173 (93.8%) patients were 30-day survivors.
      Paraplegia or paraparesis developed postoperatively in 68 (5.5%) patients. In
      patients with extent I TAAA, paraplegia and paraparesis rates in the LHB cohort
      (9 of 290, 3.1%) and those without LHB (13 of 313, 4.2%) were statistically
      similar (P=0.866). The latter was observed despite the fact that longer clamp
      times were used in the LHB group. In patients with extent II TAAA, the LHB group
      had a statistically significant lower incidence of paraplegia or paraparesis (17
      of 375, 4.5%) compared with the non-LHB group (29 of 259, 11.2%; P=0.019). In our
      experience, we identified LHB as protective for reducing the risk of
      postoperative paraplegia and paraparesis in patients who underwent the repair of
      extent I and extent II TAAA, the latter statistically significant.

PMID- 14710375
TI  - Femoro-femoral partial bypass in the treatment of thoracoabdominal aneurysms.
AB  - This article describes our rationale for the use of femoro-femoral bypass as a
      primary modality for perfusion in the repair of thoracoabdominal aortic aneurysms
      at Stanford University School of Medicine. Benefits and limitations of this
      method are discussed and compared with other described techniques.

PMID- 14710376
TI  - Regional hypothermia with epidural cooling for prevention of spinal cord ischemic
      complications after thoracoabdominal aortic surgery.
AB  - Multiple operative adjuncts have been developed and clinically applied to reduce
      the incidence of spinal cord ischemic complications (SCI) after thoracoabdominal
      aneurysm (TAA) repair. Hypothermia is known to reduce oxygen requirements in
      central nervous tissue and has been successfully applied in the arena of central
      cardioaortic surgery. Based on our experimental and clinical results, we have
      employed regional hypothermia by epidural cooling to ameliorate SCI during TAA
      repair in over 300 patients. This review describes the results obtained in our
      experience using an approach to TAA repair whereupon the spinal cord is protected
      during surgery by regional hypothermia via epidural cooling.

PMID- 14710377
TI  - The role of evoked potential monitoring in operative management of type I and
      type II thoracoabdominal aortic aneurysms.
AB  - Spinal cord ischemia with subsequent paraplegia remains the most dreaded and
      impressive complication following thoracoabdominal aortic aneurysm repair.
      Protective measures, such as cerebrospinal fluid drainage, distal aortic
      perfusion, and epidural cooling, have significantly reduced paraplegia rate. A
      major impediment is the inability to assess the efficacy of reattaching
      intercostal arteries or the contributing value of the adjunctive procedures
      during the operation. Monitoring motor-evoked potentials is a reliable technique
      to assess spinal cord integrity, dictating surgical strategies to restore and
      maintain blood supply to the gray matter. Based on motor-evoked potentials,
      hemodynamic and operative maneuvers during thoracoabdominal aortic aneurysm
      repair resulted, in our experience, in prevention of neurologic deficit in 98% of
      patients.

PMID- 14710378
TI  - The role of pharmacology in spinal cord protection during thoracic aortic
      reconstruction.
AB  - Surgery of the thoracic aorta continues to have a significant risk of neurologic
      complication. Several strategies to minimize this risk are emerging.
      Pharmacologic protection from these complications continues to be researched, but
      at this point few medications are being used clinically. This article reviews the
      pathophysiology of ischemic spinal cord injury and summarizes the investigational
      pharmacology that may prevent these serious complications.

PMID- 14710380
TI  - Ethical considerations for innovations and clinical trials.
AB  - The ethical imperative to improve practice through innovation and research finds
      justification in the requirements of physicians to help patients, minimize the
      harms of treatment and disease, and to bring the benefits of scientific medicine
      to those suffering from illnesses for which satisfactory treatment has not yet
      been developed. This article discusses the values and principles that underlie
      clinical trials; the need for evidence-based knowledge; the difference between
      research and therapy; the ethical duty to improve care through research; the
      challenge of conflict of interest; the relevance of clinical equipoise; the need
      for research review and postapproval monitoring; and the value of disseminating
      results to research subjects, colleagues, and the public. Public confidence and
      willingness to participate in clinical trials will continue if the ethical
      standards set by professional, government, and international bodies are met.

PMID- 14710381
TI  - Assessing statistical analyses of clinical trials: primer in statistical methods
      for thoracic surgeons.
AB  - Each year there are many randomized controlled trials published for thoracic
      surgeons. To apply the results of these articles to their patients, surgeons need
      to have an understanding of the criteria for assessing the validity of these
      articles. They need to be able to recognize both methodological and statistical
      flaws a study may have. This article presents a published "validity" tool that
      can be used for assessment, gives flowcharts to show which statistical tests can
      be used, and also presents the assessment findings of a review of 52 published
      randomized controlled trials. Key issues discussed include documentation of
      validity items in the methods section, overuse of P values, and correct
      statistical analyses for patients measured at various times. The article
      concludes with suggestions for future assessment and publication.

PMID- 14710382
TI  - Computerized tomography screening for lung cancer: new findings and diagnostic
      work-up.
AB  - On computerized tomography (CT) screening for lung cancer within the Early Lung
      Cancer Action Project, both at baseline and repeat screening, we found not only
      solid but also subsolid nodules, which unlike solid ones do not completely
      obscure the lung parenchyma. We established that subsolid nodules represent
      approximately 20% of the nodules shown on screening and that they have a higher
      frequency of malignancy than solid nodules. Although we found growth of solid
      nodules to be a reliable indicator of malignancy, growth of subsolid nodules was
      more difficult to assess. On review of our results to date in screening, we have
      continued to refine our definition of a positive result of screening from that
      given in our initial publication on screening. We have also provided an updated
      screening regimen. It starts with the initial, low-dose CT test and for all those
      with positive results on this initial test, the regimen continues by specifying
      the work-up needed to rule-in a diagnosis of malignancy. In this regimen, we
      found growth assessed by high-resolution CT to be a useful indicator of
      malignancy and have developed image-processing tools to help in this assessment.
      Once growth is ascertained, we recommend fine-needle aspiration for confirmation
      of malignancy. It may be that once criteria for definitive growth are established
      and validated, fine-needle aspiration may become optional. However, in the
      meantime, in the context of screening, a more cautious approach is warranted.

PMID- 14710383
TI  - Nonsmall-cell lung cancer: chemoprevention studies.
AB  - Lung cancer is the leading cause of cancer-related death in the world. Tobacco is
      an addictive agent producing carcinogenic effects that have been extremely
      difficult to prevent or detect in a curable stage. Important randomized
      controlled studies have been published in "healthy" smokers (primary prevention);
      patients with early lesions, such as mucosal dysplasia/metaplasia (secondary
      prevention); and those who have already had definitive treatment for their first
      tobacco-related malignancy (tertiary prevention). To date, the results have been
      generally disappointing. It is critical to remember that lung cancer is usually
      diagnosed decades after the patient has begun or even stopped smoking. We must
      intervene with more effective agents or combinations of agents and do it earlier
      in the process of carcinogenesis. Approximately 10% of patients with lung cancer
      either never smoked or only were "passive" smokers due to their environment,
      workplace. These "never-smokers" may actually benefit from retinoids, while
      current smokers have not benefited from alpha-tocopherol, retinal, N
      acetylcysteine, or isotretinoin. Smokers are actually harmed by the concurrent
      use of beta-carotene. We now have unprecedented knowledge regarding the control
      of cellular growth and senescence. New diagnostic tools also allow detection of
      smaller lesions. We must use all our knowledge of the cancer biology, new risk
      models, more refined intermediate markers, and modern detection tools to focus
      more clearly on the pathology of lung cancer and design research to ask more
      probing and relevant questions so we can begin to put an end to the worldwide
      scourge of this terrible killer.

PMID- 14710384
TI  - Clinical trials of peripheral stage I (T1N0M0) non-small cell lung cancer.
AB  - Debate continues regarding the choice of resection for peripheral stage I
      (T1N0M0) non-small cell lung cancer (NSCLC). Anatomic lobectomy has been
      considered the standard of care for resectable NSCLC; however, intriguing results
      of clinical trials have been reported with the use of sublobar resection as
      primary therapy of selected small peripheral lung cancers. Most modern clinical
      studies comparing lobectomy to sublobar resection of stage I NSCLC demonstrate
      equivalent survival, but local recurrence following sublobar resection appears to
      be greater. Low energy computed tomography screening programs for lung cancer
      have increasingly identified small peripheral lesions potentially amenable to
      effective therapeutic management with sublobar resection. We discuss the possible
      management scenarios for stage I NSCLC in this age of early computed tomography
      detection of lung cancer, more precise molecular biologic staging of the disease,
      optimized peri-operative management of the marginally resectable patient, and
      improved adjunctive treatment measures for local control following lung cancer
      resection.

PMID- 14710385
TI  - Results of clinical trials of multimodality therapy for resectable nonsmall-cell
      lung cancer.
AB  - More than 50% of patients presenting with so-called early stage or surgical
      disease nonsmall-cell lung cancer will die of their cancer despite resection.
      Over the years, postoperative efforts to improve the survival of these patients
      have been disappointing. There is presently a lot of enthusiasm surrounding the
      strategy of preoperative or induction chemotherapy in the treatment of such
      patients. Worldwide, at least 4 large-scale ongoing cooperative group trials are
      evaluating this question at the present time. Only by completing these trials in
      a timely manner will we know if induction chemotherapy should become the standard
      of care for all patients with surgical disease nonsmall-cell lung cancer.

PMID- 14710386
TI  - Results of clinical trials for locally advanced and metastatic nonsmall-cell lung
      cancer.
AB  - Chemotherapy in nonsmall-cell lung cancer (NSCLC) is not just a reality but has
      resulted in important improvements in quality of life and survival for patients
      with locally advanced and metastatic NSCLC. For patients with stage IV NSCLC,
      platinum-based 2-drug combinations are superior to single-agent therapy and have
      a superior therapeutic index than 3-drug combinations. Concurrent chemoradiation
      has become the standard of care for patients with locally advanced NSCLC. The
      addition of consolidation chemotherapy following definitive chemoradiation
      appears to improve median survival. The era of molecularly targeted therapies for
      NSCLC is here. Early results with some of the targeted agents studied for the
      treatment of NSCLC have generated a great deal of excitement. In this article, we
      review the results of recent clinical trials in locally advanced and metastatic
      NSCLC.

PMID- 14710387
TI  - Small-cell lung cancer: a review of clinical trials.
AB  - Small-cell lung cancer (SCLC) is expected to account for 25% of the approximate
      170,000 cases of lung cancer diagnosed in the United States in 2002. Although
      sensitive and responsive to chemotherapy, SCLC has an increased propensity for
      early metastases, with relapses being common and long-term survival rates being
      poor. Clinical trials have played a vital role in expanding our knowledge base
      for this disease and have resulted in newer modalities, including
      chemotherapeutic agents, prophylactic cranial irradiation, and thoracic
      radiotherapy designed to improve overall outcomes. Clinical trials have also
      served to clarify the role of surgery in a disease that traditionally has been
      thought to be nonoperable. This review will focus on the results of clinical
      trials that have had an effect on the treatments of patients with limited and
      extensive-stage SCLC, with recommendations from the National Comprehensive Cancer
      Network being emphasized.

PMID- 14710388
TI  - Clinical trials for pulmonary metastasectomy.
AB  - There remains great controversy as to the indications and true benefits for
      pulmonary metastasectomy. The number of metastatic lesions, length of disease
      free interval, and unilaterality has shown to be important prognostic factors on
      overall survival. In this review, we evaluate a number of clinical trials and
      critically assess the rational to perform pulmonary metastasectomy, which is a
      local treatment for a systemic disease process.

PMID- 14710389
TI  - Clinical trials in lung volume reduction surgery.

PMID- 14710396
TI  - History of antibody therapy for non-Hodgkin's lymphoma.
AB  - Monoclonal antibodies (mAbs) were the first successful targeted therapy for
      cancer. In contrast to the nonspecific nature of most chemotherapy, antibodies
      bind with high specificity to cell-surface antigens, resulting in targeted
      killing of malignant cells, relative sparing of normal tissues, and low toxicity.
      Antibody therapy has undergone substantial development since Ehrlich's notion of
      a "magic bullet," in 1890. It was not until the 1970s, however, that mAbs became
      viable as therapeutic tools and clinical studies showed them to be effective. The
      results were most impressive in hematologic malignancies, especially B-cell non
      Hodgkin's lymphoma. In 1997, rituximab (Rituxan; Genentech Inc, South San
      Francisco, CA, and Biogen Idec Inc, Cambridge, MA) became the first mAb approved
      by the US Food and Drug Administration for use in the treatment of cancer. The
      first approval for a radiolabeled antibody to treat cancer was in 2002 for (90)Y
      ibritumomab tiuxetan (Zevalin; Biogen Idec). This is a conjugate of an anti-CD20
      mAb (ibritumomab, the murine parent of rituximab) with the beta-emitter
      radionuclide (90)Y. (90)Y ibritumomab tiuxetan has been shown to be safe and
      effective in the indicated patient population. Other radioimmunoconjugates are
      being investigated for the treatment of non-Hodgkin's lymphoma, as are several
      immunotoxins. This article reviews important events in the development of mAb
      therapy and radioimmunotherapy for B-cell non-Hodgkin's lymphoma.

PMID- 14710397
TI  - Radiobiology of radioimmunotherapy with 90Y ibritumomab tiuxetan (Zevalin).
AB  - Radioimmunotherapy represents a significant advance over unlabeled immunotherapy
      for the treatment of patients with B-cell non-Hodgkin's lymphoma. The efficacy of
      radioimmunotherapeutic agents depends in large part on the basic biological
      effects associated with their components, monoclonal antibodies and
      radionuclides, separately and in combination. The radiobiological effects
      associated with yttrium 90-labeled ibritumomab tiuxetan (Zevalin; Biogen Idec
      Inc, Cambridge, MA) include the induction of apoptosis and cell-cycle
      redistribution (eg, arrest of cells in the G(2)/M phase of the cell cycle).
      Because of dose-rate effects, tumor cells may, in some cases, be more susceptible
      to the low-dose-rate radiation used in radioimmunotherapy than to the high-dose
      rate radiation used in external beam radiotherapy. The efficacy of
      radioimmunotherapy may potentially be optimized through a variety of approaches,
      including the use of agents that increase the expression of certain tumor
      antigens (thus facilitating improved biodistribution of radiolabeled monoclonal
      antibodies) or that sensitize tumor cells to radiation.

PMID- 14710398
TI  - Efficacy and safety of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy for
      non-Hodgkin's lymphoma.
AB  - Radioimmunotherapy, an emerging treatment option for certain patients with non
      Hodgkin's lymphoma (NHL), enables the targeting of cytotoxic radiation to tumor
      cells with minimal irradiation of normal cells. Yttrium 90 ibritumomab tiuxetan
      (Zevalin; Biogen Idec Inc, Cambridge, MA) was approved in February 2002 for the
      treatment of patients with relapsed or refractory low-grade, follicular, or
      transformed B-cell NHL, including patients with rituximab-refractory NHL. Yttrium
      90 ibritumomab tiuxetan is an effective treatment with a consistent overall
      response rate of 73% to 83%. It has a good safety profile and is generally well
      tolerated in the indicated population. The results of clinical trials show that
      (90)Y ibritumomab tiuxetan can be used effectively and safely in many patients
      with NHL, including those with mild thrombocytopenia and those with disease that
      is refractory to rituximab, without the adverse events associated with
      conventional chemotherapy and external beam radiation therapy. The use of (90)Y
      ibritumomab tiuxetan does not preclude subsequent therapy with other conventional
      treatment options.

PMID- 14710399
TI  - Selecting patients for treatment with 90Y ibritumomab tiuxetan (Zevalin).
AB  - Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the
      first radioimmunotherapeutic agent approved by the US Food and Drug
      Administration. It is indicated for treating patients with relapsed or refractory
      low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including
      patients with rituximab-refractory follicular non-Hodgkin's lymphoma. Proper
      patient selection is essential for optimizing the efficacy and safety of
      treatment with (90)Y ibritumomab tiuxetan. It may be advisable to use (90)Y
      ibritumomab tiuxetan relatively early in a patient's course of treatment because
      overall and complete response rates, and the estimated median duration of
      response, are higher among patients who have had fewer median prior
      antineoplastic regimens than among those who have had a greater median number of
      such regimens. Furthermore, the myeloablative effect of multiple courses of
      chemotherapy can preclude the later use of (90)Y ibritumomab tiuxetan. In
      contrast, other therapies, including chemotherapy and rituximab, can be used
      safely and successfully after (90)Y ibritumomab tiuxetan without concerns about
      increased hematologic toxicity from the previous radioimmunotherapy. The main
      adverse event associated with (90)Y ibritumomab tiuxetan therapy is hematologic
      toxicity and, as a result, only patients with adequate bone marrow reserves and
      less than 25% lymphoma marrow involvement should currently be considered for
      clinical therapy.

PMID- 14710400
TI  - Practical considerations and radiation safety in radioimmunotherapy with yttrium
      90 ibritumomab tiuxetan (Zevalin).
AB  - 90Y ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA), the first
      radioimmunotherapeutic agent approved by the US Food and Drug Administration, is
      a promising treatment option in patients with relapsed or refractory low-grade,
      follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with
      rituximab-refractory follicular non-Hodgkin's lymphoma. The ibritumomab tiuxetan
      regimen is administered on an outpatient basis over approximately 1 week and with
      the simplicity of weight-based dosing (ie, calculation of whole body clearance is
      unnecessary). Other than acrylic shielding, only universal precautions are
      required to administer (90)Y ibritumomab tiuxetan, and patient isolation is
      unnecessary. This treatment regimen requires a coordinated multidisciplinary
      approach. Oncologists play a leading role in selecting patients for (90)Y
      ibritumomab tiuxetan therapy and in prescribing and overseeing the treatment.

PMID- 14710403
TI  - [The elderly and work: the third age as vocation].

PMID- 14710401
TI  - Future directions in radioimmunotherapy for B-cell lymphoma.
AB  - Rituximab has become a staple in the management of B-cell non-Hodgkin's lymphoma,
      but it has limited activity as a single agent, with responses in about half of
      patients with recurrent follicular and low-grade lymphoma. Radioimmunotherapy
      (RIT) may surmount inherent or acquired antibody resistance by targeting a
      radionuclide to tumor cells. This strategy is particularly appealing for B-cell
      lymphoma because CD20 affords an outstanding target and lymphomas are inherently
      radiosensitive. The efficacy and safety of RIT have been established in the
      treatment of relapsed or refractory indolent non-Hodgkin's lymphoma, and yttrium
      90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first
      RIT agent to be approved by the US Food and Drug Administration. This supplement
      to Seminars in Oncology seeks to present hematologists and medical oncologists
      with the most recent developments in RIT with (90)Y ibritumomab tiuxetan for non
      Hodgkin's lymphoma, to clarify the role of the medical oncologist in the
      administration of the ibritumomab tiuxetan regimen, to indicate how and when RIT
      with (90)Y ibritumomab tiuxetan may most successfully be integrated into the
      continuum of treatment for patients with B-cell lymphoma, and to describe ongoing
      clinical trials with (90)Y ibritumomab tiuxetan in B-cell lymphomas.

PMID- 14710404
TI  - [Epidemiology in the elderly].

PMID- 14710405
TI  - [Requirements of the clinician].

PMID- 14710407
TI  - [Neuroradiologic diagnosis of dementias].

PMID- 14710406
TI  - [Physiological aging of the brain and chronic cerebral vasculopathies].

PMID- 14710408
TI  - [Diagnostic imaging of degenerative diseases of the extrapyramidal system].

PMID- 14710409
TI  - [Requirements of the clinician].

PMID- 14710410
TI  - [Osteoporosis in the elderly. Requirements of the gynecologist].

PMID- 14710411
TI  - [Bone densitometry in the diagnosis and follow-up of osteoporosis].

PMID- 14710412
TI  - [Diagnostic imaging of degenerative disease of the shoulder, hip, and knee].

PMID- 14710413
TI  - [Aging: anatomo-pathologic assessment].

PMID- 14710414
TI  - [Requirements of the elderly in modern society].

PMID- 14710415
TI  - [Requirements of the clinician].

PMID- 14710416
TI  - [Thoracic examination in cardiac aging].

PMID- 14710417
TI  - [Modern diagnostic imaging in cardiac aging].

PMID- 14710418
TI  - [Radiologic study of aging of the aorta and the coronary arteries].

PMID- 14710419
TI  - [Diagnostic imaging in aging of the peripheral vessels].

PMID- 14710420
TI  - [Requirements of the clinician].

PMID- 14710421
TI  - [Thoracic aging].

PMID- 14710422
TI  - [Radiologic study of pulmonary thromboembolism].

PMID- 14710423
TI  - [Radiologic study of heart failure in the elderly].

PMID- 14710424
TI  - [Diagnostic imaging of pneumonia in the elderly].

PMID- 14710425
TI  - [The radiologist and the elderly].

PMID- 14710426
TI  - [Problems with injectable contrast media in the elderly].

PMID- 14710427
TI  - [Requirements of the clinician].

PMID- 14710428
TI  - [Diagnostic imaging of deglutition and continence-defecation disorders].

PMID- 14710429
TI  - [Role of diagnostic imaging in intestinal diseases in advanced age (small
      intestine-colon)].

PMID- 14710430
TI  - [Radiology of the aging liver. Imaging and therapy].

PMID- 14710431
TI  - [Diagnostic imaging of the bile ducts and pancreas].

PMID- 14710432
TI  - [Inquiries of the clinician].

PMID- 14710433
TI  - [Renal tumors in the elderly].

PMID- 14710434
TI  - [Diagnostic imaging of chronic renal infections and renal infections in
      diabetes].

PMID- 14710435
TI  - [Diagnostic imaging of the bladder and prostate in the elderly].

PMID- 14710436
TI  - [Radiologic technology at the service of the elderly].

PMID- 14710437
TI  - Reduction of rat pleural microvilli caused by noise pollution.
AB  - Scanning electron microscopy (SEM) was used to investigate whether chronic
      exposure to noise modifies pleural morphology. Rats were submitted to 8-h/day
      schedule of noise that is similar to the working hours at cotton-mill rooms.
      Morphometry of the area occupied by microvilli on the pleural surface showed a
      decrease in microvilli after 3 months of rat exposure to noise. The reduction of
      microvilli was 10% after 3 months of noise exposure (reaching 20% after 7 months
      of noise treatment) and is consistent with pleural effusions found in some of the
      patients working in noise-polluted environments.

PMID- 14710438
TI  - Clara cell 10-KDA protein inhibits endotoxin-induced airway contraction in
      isolated perfused rat lungs.
AB  - Clara cell 10-kDa protein (CC10) is a major component of bronchoalveolar lavage
      fluid and is suggested to be a natural regulator of airway inflammation, possibly
      through its effects on the proinflammatory enzyme(s), phospholipase A2. We
      examined the effect of recombinant human (rh) CC10 on endotoxin-induced airway
      contraction and cytokine release in isolated perfused rat lungs. We found that
      rhCC10 added to the lung perfusate abolished the endotoxin-induced airway
      contraction, and that it inhibited both the release of interleukin-1 beta and
      interleukin-6 into the lung perfusate and the release of tumor necrosis factor
      alpha into the pulmonary lavage fluid. By contrast, the levels of interferon
      gamma were unaffected by CC10 administration. Rutin, a phospholipase A2
      inhibitor, and N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      synthase inhibitor, also attenuated the contraction induced by endotoxin. These
      findings demonstrate that rhCC10 inhibits endotoxin-induced airway contraction
      and the release of proinflammatory cytokines (interleukin-1 beta, interleukin-6,
      and tumor necrosis factor-alpha) in isolated perfused rat lungs. The results also
      indicate that phospholipase A2 and nitric oxide are involved in the airway
      contraction in this model, possibly through their influence on the production of
      eicosanoids.

PMID- 14710439
TI  - Pulmonary deposition of monodisperse aerosols in patients with chronic
      obstructive pulmonary disease.
AB  - In order to improve patient convenience and drug availability for patients with
      alpha 1-protease inhibitor deficiency, the administration via the inhalation
      route has been considered. This study investigated if it is possible to obtain
      high values of peripheral aerosol deposition by using optimized and controlled
      inhalation conditions. Therefore, peripheral deposition was studied in 10
      patients with alpha 1-protease inhibitor deficiency (phenotype PiZ) and moderate
      to severe chronic obstructive pulmonary disease by measuring the 24-hour
      Clearance of radiolabeled inert iron oxide particles with diameters of 2 microns,
      3 microns, and 4 microns. Patients inhaled a large volume of aerosol (1000 to
      2000 cm3), which was normalized to the individual lung function, with a flow rate
      of 200 cm3/S. Due to this breathing pattern, peripheral deposition was for all
      particle sizes above 50% of the inhaled aerosol. The highest peripheral
      deposition (68%) was found for 3-microns particles.

PMID- 14710440
TI  - Chronic zinc deficiency induces an antioxidant adaptive response in rat lung.
AB  - Few studies are available about the role of dietary zinc (Zn) in respiratory
      diseases. Adult male rats were divided into 2 groups and fed respectively a
      moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2
      months, thiobarbituric acid-reactive species (TBARS), total glutathione,
      glutathione disulfide, protein carbonyls, metallothionein, and the activities of
      glutathione peroxidase (GPx), catalase, CuZn-superoxide dismutase (CuZnSOD) and
      glucose-6-phosphate dehydrogenase (G-6-PDH) were increased, but protein thiols
      decreased. In lung tissue at 4 months, TBARS, metallothionein, and the activities
      of CuZnSOD, Mn-superoxide dismutase (MnSOD) increased. The activities GPx,
      catalase, G-6-PDH were lower than control group. The changes were accompanied by
      histological alterations in Zn-deficient lung. The results provide evidence of
      the pro-oxidative effects of Zn-deficiency in lung, and suggest that the time of
      treatment play a key role in determining lung susceptibility to oxidative stress.

PMID- 14710441
TI  - Heterogenous and compartment-specific activation of nonlymphocytic, mononuclear
      cells in intraabdominal sepsis.
AB  - Although sepsis is associated with increased production of cellular pro- and anti
      inflammatory mediators by monocyte/macrophages, the compartmentalization and
      nature of such activation has not been clearly defined. The authors examined the
      activation of nonlymphocytic mononuclear cells in different compartments in the
      cecal ligation and puncture (CLP) model of septic peritonitis. Control and CLP
      rat mononuclear cells from the peritoneal cavity, bronchoalveolar, as well as the
      lung vascular compartment were isolated 24 and 48 hours post surgery and release
      of nitric oxide (NO), interleukin (IL)-12, and monocyte chemoattractant protein-1
      (MCP-1) was measured from culture media. Peritoneal macrophages (PMs) from CLP
      rats increased release of all three mediators compared to controls. Cells from
      the lung vascular compartment after CLP increased release of NO, but MCP-1
      release was unchanged. Levels of IL-12 were not detectable. Similarly,
      bronchoalveolar macrophages (BMs) of CLP rats had increased release of NO,
      whereas IL-12 was not detectable. Release of MCP-1 increased 48 hours after CLP.
      Almost all PMs and BMs possessed innate phagocytic ability that was not altered
      during sepsis. The percentage of cells in the lung vascular compartment that had
      phagocytic ability, increased 48 hours post CLP, versus controls. The authors
      also evaluated lung injury at 24 hours after surgery by measurement of
      bronchoalveolar lavage protein and LDH activity. There was an increase in both
      these parameters 24 hours after CLP as compared to controls. Thus, there was
      heterogenous and compartment-specific activation of mononuclear cells in sepsis.
      There was nonspecific inflammatory activation in the primary site of injury. In a
      remote organ (lung), the authors show for the first time that there was selective
      activation of NO without increased release of the proinflammatory cytokine, IL
      12. Phagocytic activity was maintained in the bronchoalveolar compartment whereas
      in the lung vascular compartment, the percentage of phagocytic cells increased.

PMID- 14710442
TI  - Depletion of glutathione S-transferase P1 induces apoptosis in human lung
      fibroblasts.
AB  - Glutathione S-transferase P1 (GSTP1) is one of the xenobiotic-metabolizing and
      antioxidant enzymes, identified in the peripheral lungs. Recently, the authors
      reported the association between GSTP1 gene polymorphism and susceptibility to
      chronic obstructive pulmonary disease (COPD), and protective effect of GSTP1
      against cigarette smoke in human lung fibroblasts in vitro. In this study, the
      authors investigated that depletion of GSTP1 by itself could induce cell death,
      including apoptosis, in human lung fibroblast-derived HFL-1 cells. The level of
      apoptosis and necrosis was increased significantly with GSTP1 antisense vector
      transfection. It was also observed that the transfection efficiency and the
      expression level of the vector were weaker in the transfectant of the antisense
      vector than in those of the sense and control vectors, which is also thought to
      indicate that inhibition of GSTP1 expression by the antisense vector alone
      affects cellular viability. However, there was no difference among these
      transfectants neither on glutathione (GSH) level nor on c-Jun NH2-terminal kinase
      (JNK) activation. Therefore, the authors report here that underexpression of
      GSTP1 appeared to induce apoptosis on lung fibroblasts, which suggests that GSTP1
      may have protective effects against apoptosis in the airway cells, though the
      mechanism of this apoptotic pathway is still to be elucidated.

PMID- 14710443
TI  - [PHRC REAL.FR: French network on Alzheimer's disease].

PMID- 14710444
TI  - [The French network multicenter study. Predictive factors of hospitalization and
      management of Alzheimer's disease patients (REAL.FR)].
AB  - We present in this article the REAL.FR research program on Alzheimer disease (AD)
      and its management. This is a French multicenter prospective study whose
      objectives are to study the natural history of AD and the modalities of its
      management. In order to pursue these aims, we set up a cohort of 700 AD patients
      in France. They entered the study in year 2000 and will be followed for at least
      four years. The study population consists of AD patients, living in the community
      at the time of enrollment and looked after by an informal caregiver. On
      inclusion, each patient underwent a full investigation which included
      gerontological and social evaluation. Patients will be seen every six months for
      at least four years. During follow-up, events which have occurred during the
      previous six months are noted (i.e. admissions to hospital or to an institution,
      use of new in-home help services...). To date, 577 patients have been reviewed at
      6 month, 489 at 12 month, 358 at 18 month, 266 at 24 month, 178 at 30 month and
      31 at 36 month. 48 death have been registered, 42 patients have been
      institutionalised and 124 have been dropped out. Mean age of patients on
      inclusion was 77.4 +/- 7 years. Nearly one-third of patients were living at home
      when they were enrolled in the study. Our preliminary results are encouraging
      regarding the feasibility of patients follow-up. The satisfactory participation
      of patients and their families in the later evaluations which have already been
      carried out also seem promising for the continuation of follow-up.

PMID- 14710445
TI  - [Clinical evaluation of dementia in a cohort of 358 patients with the French
      version of the Clinical Dementia Rating (CDR) scale].
AB  - PURPOSE: A reliable global rating of dementia severity in Alzheimer's disease is
      critical both in clinical and research practice. In this paper, we present the
      results of the assessment of a cohort of 358 patients using the French version of
      the Clinical Dementia Rating Scale (CDR). METHODS: 358 patients from a
      multicentric cohort were assessed in a comprehensive way: cognitive (Mini Mental
      Status Examination), functional (Activities of Daily Living), behavioural (Neuro
      Psychiatric Inventory) and global (Global Dementia Scale). CDR staging was
      performed after both patient and caregiver interview. RESULTS: 27.6% of the
      patient had a CDR 0.5 (questionable dementia), 43% CDR 1 (mild dementia), 24.9%
      CDR 2 (moderate dementia) and 4.5% CDR 3 (severe dementia). All the rating scales
      were highly correlated with CDR stages (p < 0.0001). The CDR was also correlated
      with the Global Dementia Scale (p < 0.0001), but a perfect overlap of individual
      stages was not achieved. CONCLUSIONS: CDR staging takes into account the major
      domains of dementia assessment: cognition, function and behaviour. Staging
      Alzheimer's patients as CDR 0.5 arises the issue of the relationship between very
      mild dementia and Mild Cognitive Impairment. This study represents the first step
      of the CDR (French version) validation which is underway in this cohort.

PMID- 14710446
TI  - [Vascular risk factors and Alzheimer's disease].
AB  - BACKGROUND AND OBJECTIVE: Recent epidemiological study and clinico-pathologic
      data suggest overlaps between Alzheimer disease and cerebrovascular lesions that
      may magnify the effect of mild Alzheimer disease pathology and promote
      progression of cognitive decline. There is now strong epidemiologic evidence
      supporting an association between Alzheimer disease and two major vascular risk
      factors--blood pressure and diabetes. The major objective of this study is to
      analyse the impact of vascular risk factors on natural history of Alzheimer's
      disease. METHODS: Descriptive analyse of the vascular risk factors on 520
      Alzheimer's disease patients issue from the population of the "Programme
      Hospitalier de Recherche Clinique: "Reseau sur la maladie d'Alzheimer francais".
      RESULTS: The description of the vascular risk factors in the Alzheimer's disease
      patients from the "Programme Hospitalier de Recherche Clinique. "Reseau sur la
      maladie d'Alzheimer Francais" was made and the projects and perspectives of
      analyses based on the longitudinal data were discussed. 45% of subjects have high
      blood pressure, they were significantly older (p < 0.05), have more frequent
      impairment of ADLs (p < 0.05), and one-leg balance impairment (p < 0.05). 10% of
      patients have diabetes and 23.95% hypercholesterolemia. CONCLUSIONS: The first
      data on vascular risk factors of the "Programme Hospitalier de Recherche
      Clinique: "Reseau sur la maladie d'Alzheimer francais"" are the first step on
      comprehension of the impact of vascular risk factors and their traitments on
      Alzheimer's disease.

PMID- 14710447
TI  - [Relationship between arterial pressure and cognitive functions. Data for the
      French Network on Alzheimer's disease (REAL.FR)].
AB  - The relationships between arterial hypertension and cognitive decline are complex
      and studies indicate controversial results. OBJECTIVES: To evaluate, in a cross
      sectional study, the relationships between cognitive functions and blood pressure
      in a population of subjects with Alzheimer's disease. METHODS: In 520 subjects of
      a survey in a French population with Alzheimer's disease, relationships between
      the severity of cognitive decline and a history of hypertension or blood pressure
      level have been searched. Cognitive functioning was assessed with validated
      neuropsychological tests evaluating cognitive functions and the capacities in the
      activities of daily living (Mini Mental State Examination (MMSE), Alzheimer's
      Disease Assessment Scale--Cognitive part (ADAS-Cog), Instrumental Activities of
      Daily Living (IADL), Activities of Daily Living (ADL), Clinical Dementia Rating
      (CDR), Global Deterioration Scale (GDS) of Reisberg). In 456 subjects blood
      pressure was measured during the consultation. RESULTS: The results indicate that
      after adjustment on age, sex, education level, and the other cardiovascular risk
      factors, subjects with a history of hypertension have a more marked cognitive
      decline than subjects without history of hypertension. Indeed, in subjects with a
      history of hypertension, the cognitive impairment and its consequences on
      activities of daily living are more important than in subjects without history of
      hypertension (ADAS-cog 19.02 +/- 8.48 vs 17.49 +/- 8.53 p = 0.06, MMSE 19.55 +/-
      4.41 vs 20.30 +/- 4.42, p = 0.08, score ADL 5.31 +/- 0.86 vs 5.51 +/- 0.87, p =
      0.01, CDR 6.94 +/- 3.29 vs 6.19 +/- 3.26 p = 0.03; global CDR 1.18 +/- 0.62 vs
      1.05 +/- 0.60, p = 0.03, GDS of Reisberg 4.41 +/- 0.74 vs 4.27 +/- 0.75, p =
      0.05). In contrast, no relation between blood pressure measurements and cognitive
      function is observed, and moreover an inverse correlation between blood pressure
      and consequences on activities of daily living is found. CONCLUSIONS: This work
      indicates that relationships between blood pressure and cognitive functions are
      more complex than a simple linear relation. The present results show that a
      history of arterial hypertension is associated with a more marked cognitive
      decline in subjects with Alzheimer's disease. In contrast, when the Alzheimer's
      disease is already developed no relation between blood pressure and cognitive
      functions appears and moreover an inverse correlation with the consequences on
      activities of daily living is found.

PMID- 14710448
TI  - [Patients with Alzheimer's disease living alone at home in the cohort of
      REAL.FR].
AB  - OBJECTIVE: Despite the French population's growing, we reported an increasing
      numbers of older adults living alone and an increasing number of older adults
      with Alzheimer's disease. Social and medical problems may be exacerbated with
      subjects with both phenomena. The objective is to identify differences in
      patterns between persons with dementia who live alone versus living with some
      people at home. METHOD: 700 subjects with mild to moderate Alzheimer's disease
      from the French Alzheimer network (REAL.FR). We studied social and demographic
      feature, nutritional and cognitive statute and a comprehensive geriatric
      assessment. RESULTS: In this study, 28% of subjects with probable or possible
      Alzheimer's disease live alone. They are more likely to be women (p < 0.001) with
      few physical impairments (p < 0.02). Subject are more frailty: lower incomes,
      impairment in the nutritional status and balance, and are more likely to use
      medical and non medical services (p < 0.0001). They are more likely to be
      malnourished than the others. On the other hand, there is no association between
      disability's cognitive levels and living alone. CONCLUSION: We need longitudinal
      survey to follow up this population to determine predicting factors for keeping
      them alone at home and to anticipate long-term care placement.

PMID- 14710449
TI  - [Clinical features of ambulatory patients over 80 years of age followed for
      Alzheimer's disease. French prospective multicenter study REAL.FR].
AB  - PURPOSE: Twice out off three, patients with Alzheimer's disease (AD) are aged 80
      and older. Very old patients are more frail, have social precariousness and have
      often polypathology. Few data are available about these elderly patients. The aim
      of our study was to analyse characteristics of AD patients aged 80 and older.
      MATERIAL AND METHODS: This is a prospective, multicentric French study (REAL.FR)
      of a cohort of ambulatory AD patients, with Mini-Mental State values between 10
      and 26. Clinical and social data at inclusion of patients aged 80 and older and
      patients younger were compared. RESULTS: Six hundred eighty nine patients (488
      women, 201 men) were included between April 2000 and June 2002. The mean age was
      77.8 +/- 6.9 years. Two hundred sixty four patients (38%) were aged 80 and older.
      Those patients were more dependant for Activities of Daily Living (ADL) than
      younger patients (ADL score of Katz: 5.2 +/- 1.07 et 5.6 +/- 0.74 respectively; p
      < 0.001 and IADL (Instrumental Activities of Daily Living) score of Lawton: 7.3
      +/- 3.57 et 9.3 +/- 1.57 respectively; p < 0.001). Duration of evolution of the
      disease were comparable between older and younger patients. CONCLUSION: In our
      cohort, AD patients aged 80 and older had a weakest autonomy for the ADL than
      younger patients with the same stage of the disease. Results has implications on
      care. Following the cohort will permit to specify evolution of data.

PMID- 14710450
TI  - [Nutritional status and Alzheimer's disease: preliminary results of the REAL.FR
      study].
AB  - Weight loss is common in elderly people with dementia, particularly those with
      Alzheimer' disease (AD), and feeding difficulties are major issues in their care
      in the later stages of the disease. In this study (REAL FR for Reseau sur la
      maladie d'Alzheimer Francais) we prospectively used the Mini Nutritional
      Assessment (MNA) to examine the nutritional status of 479 subjects. Three groups
      of patients were studied: group 1 = 22 patients with undernutrition (MNA = 17),
      group 2 = 166 patients with risk of undernutrition (17 < MNA < 24), and group 3 =
      291 patients without undernutrition (MNA = 24). Correlations with behavioral and
      psychological signs and symptoms of dementia (Neuropsychiatric Inventory NPI),
      with caregiver distress (Zarit), and with the Mini Mental State Examination
      (MMSE) were studied. Undernutrition is more frequently associated with low MMSE
      (p < 0.001), high behavioural disturbances (p < 0.001) and high distress of
      caregivers (p < 0.001). Risk of undernutrition is also associated with NPI (p <
      0.001) and Zarit (p < 0.001). These first results in a French cohort of patients
      with AD underline the importance of the evaluation of nutritional status and
      finally the follow-up of eating behavior, cognitive status and the quality of
      life of the caregivers.

PMID- 14710451
TI  - [Behavioral and psychologic symptoms in Alzheimer's disease: results of the
      REAL.FR study].
AB  - Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) are important
      manifestations of Alzheimer's Disease (AD) and other forms of dementia, because
      they are associate with care-giver distress, increase the likelihood of
      institutionalization, and may be associated with more rapid cognitive decline In
      this study (REAL.FR for Reseau sur la maladie d'Alzheimer Francais) we
      prospectively used the Neuropsychiatric Inventory NPI to examine BPSD. 255 AD
      patients with a Mini-Mental State Examination (MMSE) score between 11 and 20 and
      244 AD patients with a MMSE between 21 and 30 were examined. Factor analysis was
      carried out leading to three different syndromes according to the level of
      cognitive impairment. BPSD were detected in 92.5% of the patients with a MMSE
      between 11 and 20, and in 84% of the patients with a MMSE between 21 and 30.
      Apathy was the most common abnormality, followed by anxiety and dysphoria. These
      results in a French cohort of patients with AD underline the importance of the
      evaluation and finally of the treatment of BPSD.

PMID- 14710452
TI  - [Depressive symptoms in Alzheimer's disease: preliminary results of the REAL.FR
      study].
AB  - The Alzheimer's disease (AD) is today regarded as a degenerative pathology with a
      serious and common complication: occurrence of mental and behavioral
      disturbances. Among this neuropsychiatrics symptoms, the depressive symptoms
      occupy a significant place by their frequency and their consequences on the
      caregiver's burden. The prevalence of such disorders is very variously
      appreciated in the literature. OBJECTIVE: To assess with precision depressive
      symptoms in a population with Alzheimer's disease rated on neuropsychiatric
      inventory NPI. METHOD: Cross-sectional study of patients with AD presenting at
      the consultation of psycho-geriatic, geriatric or neurologic services in 16
      french university hospitals. The frequency of the depression was evaluated with
      the NPI on a population of 578 subjects with AD. We studied the association
      existing between these symptoms and the antecedents of depression and we studied
      the gravity of these disorders according to the cognitive status. RESULTS:
      Caregivers describe less one depressive symptom for approximately 40% of the
      subjects included in the study n = 229. The average score of gravity is close to
      4 and is thus clinically significant. More the stage of dementia is severe more
      the number of subjects presenting a clinically significant score is important.
      Scores of depression evolve parallel to the stage of dementia. The antecedents of
      depression are a risk factor for depressive symptoms in the AD p < 0.001.
      DISCUSSION: These results confirm those of primary studies. In our study, more
      than the prevalence of depressive symptoms it seems that is the severity of the
      disorder which is associated with the dementia severity. The continuation of this
      work will allow a prospective evaluation of depressive symptoms in the AD.

PMID- 14710453
TI  - [Wandering and Alzheimer's type disease. Descriptive study. REAL.FR research
      program on Alzheimer's disease and management].
AB  - PURPOSE: Wandering is a common problem among patients with Alzheimer's disease.
      Few studies have examined this problematic behaviour in the community. The aim of
      the present study was to increase our understanding of wandering during
      Alzheimer's disease in subjects living in the community. METHODS: We studied 571
      patients with Alzheimer's disease living in the community. Objective cognitive
      status was assessed using a series of standardized neuropsychological tests.
      Nutritional assessment, risk of fall, autonomy were assessed as well as the
      burden of their family. The behavioural abnormalities of patients were assessed
      with their caregiver using the Neuro-Psychiatric Inventory. Patients with or
      without wandering were described. RESULTS: Prevalence of wandering was 12.6%.
      Patients with wandering appeared to have more severe cognitive impairment, less
      autonomy and were undernourished. Behavioural and psychological signs
      significantly associated with wandering were delirium, aggressiveness,
      irritability, depression, anxiety, euphoria, apathy, desinhibition and eating
      behaviour disorder. Subtype of Alzheimer's disease patients seemed to have
      frontal release behaviour. CONCLUSION: Wandering is a common behaviour in
      Alzheimer's disease patients living in the community. Special care must be
      organized to help those frail patients and their caregivers.

PMID- 14710454
TI  - [Factors associated with the moderately severe stage of Alzheimer's disease:
      first results of the REAL.FR study].
AB  - OBJECTIVE: Most studies of Alzheimer's disease deal with the mild to moderate
      stages of the disease. However the great majority of cases evolve toward a stage
      of marked severity which can last many years. The few studies of severe dementia
      that have been carried out have included institutionalized patients. The aim of
      this study is to describe associated factors with a moderately severe Alzheimer's
      disease in a French community dwelling patients. METHODS: Initial data from a
      French cohort Study of Alzheimer's patients (REAL.FR: Reseau sur la maladie
      d'Alzheimer francais) were analysed. These included sociodemographic and medical
      factors and measures of cognitive and non cognitive performance. We compared two
      groups according the stage of the disease: moderately severe patients (Mini
      Mental Status score < 15) and mild to moderate patients (Mini Mental Status score
      > or = 15). RESULTS: Moderately severe stage of disease was independently related
      to age (OR: 0.35; 95% CI: 0.16-0.78 for patient aged between 75-80 years compared
      to patient < or = 75 years), low educational level (non-obtention of french
      certificate of primary education, OR: 2.43; IC a 95%: 1.28-4.59) and disability
      to perform activities of daily living (OR: 3.35; 95% CI: 1.62-6.93). After
      multivariate analysis, there was no difference between the 2 groups for the other
      factors like behavioral symptoms. CONCLUSIONS: Severe dementia represents major
      medical and socio-economical problem. Better knowledge of the natural history of
      the severe stage of the disease is necessary for better clinical practice.

PMID- 14710455
TI  - [Rapid loss of the Mini Mental State Examination: REAL.FR study].
AB  - BACKGROUND: Alzheimer's disease is a chronic pathology requiring regular follow
      up. The predictive factors of rapid cognitive decline remain unclear. OBJECTIVES:
      To analyse the baselines characteristics of patients at increased risk of rapid
      cognitive decline. METHODS: This study presents transversal data on a community
      based sample of 340 patients diagnosed with probable Alzheimer's disease and
      followed by REAL.FR group. Rapid cognitive decline was defined as a 3-points or
      greater loss on the Mini Mental State Examination (MMSE) within six months.
      RESULTS: 54% of patients presented a rapid cognitive decline. Logistic regression
      analysis showed a positive association between rapid cognitive decline and a MMSE
      < or = 20 (p < 0.003) or a greater BMI (p < 0.02) and a tendency towards a
      negative correlation with anxiety (p = 0.06) and negative correlation with the
      burden severity (p < 0.05). CONCLUSIONS: Patients with a worse cognitive status,
      a greater BMI and less anxiety or burden were at increased risk of rapid
      cognitive decline. Future studies should focus on determining etiologies for
      patients with rapid cognitive loss and help clinicians target these patients for
      interventions aiming to delay or stabilise the course of this disease.

PMID- 14710456
TI  - [Burden experienced by informal caregivers assisting Alzheimer's patients in the
      REAL.FR study].
AB  - BACKGROUND: Most AD patients are cared for at home by informal caregivers. The
      effect of different kind of stressors on caregivers has been referred to as
      caregiver burden. OBJECTIVE: To determine (1) the level of burden of informal
      caregivers of Alzheimer's patients in a French national sample; (2) the factors
      associated with a high level of burden. METHODS: Cross-sectional study of
      informal caregivers of the demented elderly referred to a psychogeriatric,
      geriatric or neurological service. The principal caregivers of 531 patients with
      mild to moderate dementia attending an outpatient cognitive assessment clinic
      were interviewed via a structured questionnaire that focused upon caregiver
      related characteristics such as whether they were living with the patients, their
      feelings of burden assessed by the Zarit Burden Interview and patients were
      examined at baseline to evaluate their cognitive, behavioral and functional
      limitation. RESULTS: Logistic regression analysis showed that patients'
      characteristics (MMSE, behavioral problems, nutritional problems), caregiver's
      characteristics (female gender, number of tasks involved in caregiving,
      cohabitation) and the provision of medical services were independently associated
      with a high level of burden. In this study increased caregiver burden was related
      independently to increased levels of patient behaviour disturbance and cognitive
      impairment. However, neither the illness duration nor the functional disabilities
      in activities of daily living affected the level of burden. This may have
      relevance to appropriate interventions for informal caregivers.

PMID- 14710457
TI  - New paradigms for research on heterosexual and sexual-minority development.
AB  - As psychological research on sexual-minority (i.e., nonheterosexual) adolescents
      has increased over the past 20 years, it has become increasingly segregated from
      research on mainstream heterosexual youths, as if the knowledge gleaned from each
      population had nothing to offer our understanding of the other. To the contrary,
      understanding of both populations would be greatly improved by integrating
      investigations of sexual-minority issues into mainstream psychological research
      on adolescents. I outline 4 weaknesses in contemporary research on sexual
      minority youth that stem from--and perpetuate--its historical isolation from
      mainstream developmental research: misspecification of the populations under
      study, lack of attention to within-group diversity, failure to test alternative
      explanations for--and moderators of--"sexual-minority effects," and insufficient
      attention to the underlying processes and mechanisms through which sexual
      minority effects operate. Correcting these weaknesses has important implications
      for future research on how same-sex and other-sex sexuality shape adolescent
      psychosocial development and clinical child and adolescent problems.

PMID- 14710458
TI  - Adolescent romance and emotional health in the United States: beyond binaries.
AB  - Research on adolescent same-sex sexuality has focused almost exclusively on risk
      in the lives of self-identified lesbians, gays, and bisexuals. The attention to
      same-sex self identity may obscure heterogeneity in same-sex romance (attractions
      and relationships) and thus may inaccurately characterize sexual-minority youth
      as more different than heterosexual youth in terms of emotional health risk.
      Using data from the National Longitudinal Study of Adolescent Health, we examine
      the nexus of romantic attractions and relationships among contemporary U.S.
      adolescents, linking experiences of romance to indicators of emotional health. We
      conclude that broadening the scope of inquiry beyond binaries of identity (that
      is, gay vs. straight) provides the opportunity to more fully understand the
      health and well-being of all adolescents.

PMID- 14710459
TI  - Suicide attempts among sexual-minority male youth.
AB  - The purpose of this study was to provide data addressing Diamond's (this issue) 4
      problem areas in sexual orientation research by comparing gay, bisexual, and
      questioning male youth who report attempting suicide with those who do not.
      Secondary analyses were conducted with 2 datasets, 1 with a gay support group (n
      = 51) and the other with online youth (n = 681). Reported suicide attempts ranged
      from 39% among support-group youth, to 25% among Internet gay support group
      youth, to 9% among Internet non-support group youth. Sexual orientation,
      behavior, and identity did not predict suicidal attempt status, but suicide
      attempters experienced higher levels of both generic life stressors (low self
      esteem, substance use, victimization) and gay-related stressors, particularly
      those directly related to visible (femininity) and behavioral (gay sex) aspects
      of their sexual identity. Support-group attendance was related to higher levels
      of suicidality and life stressors, as well as certain resiliency factors. Results
      suggest that there exists a minority of sexual-minority youth who are at risk but
      that it would be inappropriate to characterize the entire population as such.

PMID- 14710460
TI  - Mom, dad, I'm straight: the coming out of gender ideologies in adolescent sexual
      identity development.
AB  - Little attention has been given to how femininity and masculinity ideologies
      impact sexual-identity development. Differentiating violations of conventional
      femininity and masculinity ideologies as part of an overt process of sexual
      identity development in sexual-minority adolescents suggested the possibility of
      a parallel process among heterosexual adolescents. Based on feminist theory and
      analysis of heterosexual adolescents narratives about relationships, the
      importance of negotiating femininity and masculinity ideologies as part of sexual
      identity development for all adolescents is described.

PMID- 14710461
TI  - Extending the boundaries of research on adolescent development.
AB  - The mainstream psychology literature has historically failed to include
      individuals with nonheterosexual sexual orientations in its study of many areas,
      including adolescent development, sexual development, psychotherapy, couple
      relationships, aging, suicide, and substance abuse. The articles contained in
      this issue make clear that knowledge of human behavior will be more complete when
      research designs are expanded to reflect more accurately the diversity of sexual
      orientations and sexual expressions. Furthermore, when sexuality is categorized
      into a rigidly defined group like lesbian, gay, bisexual, and transgender (LGBT),
      it constrains the ways in which individuals might otherwise think about it.
      Knowledge of human behavior will be advanced more effectively when the field of
      psychology integrates people of diverse and complex sexualities into its research
      and studies the mediators and moderators associated with this diversity.

PMID- 14710462
TI  - Positive events as a stress buffer for children and adolescents in families in
      transition.
AB  - This study examined whether positive events mitigated the relation between
      negative events and maladjustment in samples of children and adolescents
      experiencing family transitions. The study examined this relation in two samples,
      used multiple reporters of maladjustment, and employed "tailor-made" checklists
      to measure events. The first sample included 86 stepfamilies with adolescents 10
      to 17 years of age. The second sample included 171 divorced families with
      children 8 to 15 years of age. Evidence that positive events are protective for
      children and adolescents experiencing high levels of negative events was found
      across the 2 samples and across mother and child report of adjustment. These
      findings have implications for theory and intervention development.

PMID- 14710463
TI  - Popularity, friendship quantity, and friendship quality: interactive influences
      on children's loneliness and depression.
AB  - A mediational model positing that the effects of popularity on children's
      loneliness and depression are passed through indexes of friendship experiences
      was tested using structural equation modeling. Children (193 3rd through 6th
      graders) completed a battery of sociometric and self-report questionnaires from
      which measures of popularity, multiple friendship dimensions (i.e., quantity and
      quality of best and good friendships), and loneliness and depression were
      derived. Confirmation of a slightly modified model supported the mediational
      hypothesis. Although popularity exerted no direct impact on the adjustment
      indexes, it strongly influenced friendship, which, in turn, affected depression
      through its strong association with loneliness. It appears that popularity is
      important for setting the stage for relationship development, but that it is
      dyadic friendship experiences that most directly influence feelings of loneliness
      and depression.

PMID- 14710464
TI  - Elementary school age children's future intentions and use of substances.
AB  - This study describes the lifetime prevalence and future intentions related to
      trying cigarettes, chewing tobacco, alcohol, marijuana, and inhalants of students
      in the 1st through 7th grade. This article also describes the identification of
      these substances by children in the 1st through 3rd grade. Participants were
      1,075 1st through 5th graders within a school district in western Oregon who were
      followed for 3 years. Across most substances, prevalence and intentions increased
      with grade, with a moderate increase between 3rd and 4th grade and a larger
      increase between 5th and 6th grade. Boys were more likely than girls to identify
      alcohol and cigarettes and were more likely than girls to report trying chewing
      tobacco. In addition, 3rd-grade boys were more likely to identify marijuana and,
      in the early grades, alcohol. Boys were also more likely than girls to intend to
      use tobacco and drink alcohol when older. For alcohol and cigarettes, intention
      was related to subsequent trying of the substance, suggesting that intention may
      be an early warning sign of subsequent substance use.

PMID- 14710465
TI  - Aggressive and nonaggressive boys' physiological and cognitive processes in
      response to peer provocations.
AB  - This study examined physiological and social-cognitive correlates of aggression
      in an in vivo laboratory provocation situation. Fifty-one male participants (ages
      9 to 13) were selected based on teacher aggression screenings, ranging from
      normative to high levels. A provocation was induced by the experimenter
      communicating a threat from an unseen "peer" in the laboratory. Bivariate linear
      regression analyses showed that aggression significantly predicted heart rate at
      both pre- and postinduction, and aggression significantly predicted attributions
      of intent following the provocation. Results indicated that aggression was a
      significant predictor of changes in hostile attribution and heart rate following
      the threat induction. A positive correlation also was found between heart rate
      change and attribution change. The findings suggest that both physiological and
      social-cognitive processes should be addressed in clinical interventions with
      aggressive children.

PMID- 14710466
TI  - Callous/unemotional traits moderate the relation between ineffective parenting
      and child externalizing problems: a partial replication and extension.
AB  - We replicated and extended Wootton, Frick, Shelton, and Silverthorn's (1997)
      finding that children's callous/unemotional (C/U) traits moderated the
      association between poor parenting and children's externalizing problems. C/U
      traits were indexed (a) as dichotomous scores (D-C/U) above or below a cut score
      on the original C/U subscale and (b) as continuous scores (C-C/U-R) on the
      revised C/U subscale. Results did not support a moderating role for D-C/U scores,
      but significant interactions were found between C-C/U-R scores and poor parenting
      when predicting teachers and peers ratings of externalizing behavior. Poor
      parenting was unrelated to problem behavior in children with relatively high C
      C/U-R scores.

PMID- 14710467
TI  - Community violence and children's psychological well-being: does parental
      monitoring matter?
AB  - Poor, inner-city children are exposed to inordinately high rates of community
      violence. Although the link between exposure to violence and adverse mental
      health outcomes is well documented, less attention has focused on factors that
      may buffer children from negative outcomes. Using a sample of 163 4th- and 5th
      grade children, this study investigated whether children's perceptions of
      parental monitoring moderate the relation between children's violence exposure
      and their psychological well-being, as assessed by depression and hopelessness.
      Greater exposure to community violence was associated with more symptoms of
      depression and feelings of hopelessness. Moreover, parental monitoring buffered
      to a certain extent the relation between violence exposure and psychological
      functioning. Increased monitoring had a positive impact on the psychological well
      being of children who were less exposed to violence; however, as violence
      exposure increased, the impact of parental monitoring was attenuated.

PMID- 14710468
TI  - Separation anxiety disorder in young children: a longitudinal and family
      analysis.
AB  - We conducted a longitudinal study of young children with clinical, subclinical,
      or nonclinical levels of separation anxiety to evaluate the diagnostic stability
      and concomitant parent and family variables of separation anxiety disorder (SAD).
      Youngsters were assessed at age 3 years (n = 60) and 3.5 years later (n = 44).
      Data were collected from children, parents, teachers, and clinicians. Results
      revealed that most diagnoses of SAD were not stable during this developmental
      period, as many children drifted toward subclinical or nonclinical status. In
      addition, children with clinical SAD, compared to those with subclinical SAD or
      no symptoms of SAD, had a disproportionately higher number of comorbid diagnoses
      and experienced significantly greater somatic concerns, anxiety, and general
      internalizing behavior. In addition, their parents experienced greater
      depression, obsessive-compulsive behavior, phobic anxiety, and general distress.
      The results preliminarily support prior findings that most children experience a
      dissipation of SAD symptoms in young childhood but that some children continue to
      experience stable, significant distress. The results are consistent with prior
      research on older children that SAD remits for many but not all youth and suggest
      that parent and family variables may have much to do with cases of poor remission
      in this population.

PMID- 14710469
TI  - Father involvement in parent training: when does it matter?
AB  - We examined the impact of father involvement on treatment. Participants were 107
      families enrolled in parent-child interaction therapy (PCIT), including 56
      involved-father (IF) families, 16 uninvolved-father (UF) families, and 35 absent
      father (AF) families. All groups showed improvements during treatment to within
      the average range on the Eyberg Child Behavior Inventory (ECBI), although mothers
      from AF families reported better treatment outcome than mothers from IF families.
      Improvements occurred on the Beck Depression Inventory (BDI) and the Parenting
      Stress Index (PSI) as well, but there were no group differences. At a 4-month
      follow-up, mothers in IF families maintained treatment gains on the ECBI. In
      contrast, mothers in AF families reported significant decline at follow-up,
      although their scores remained within the normal range. Results suggest that
      father participation in treatment may not affect immediate treatment outcome but
      may help to maintain the beneficial effects of PCIT.

PMID- 14710470
TI  - Longitudinal correlates of depressive symptoms among urban African American
      children: II. Extension of findings across 3 years.
AB  - We examined the association between childhood self-reported depressive symptoms
      and 2 areas of child psychosocial functioning: social and cognitive competence.
      Urban African American children, ages 6 to 11 and their mothers (N = 177) were
      interviewed at 2 assessments separated by 3 years. As a test of the relations
      among depressive symptoms and subsequent psychosocial functioning, independent
      hierarchical regression analyses were performed, with mother-reported social and
      cognitive competence and grades at the latter assessment as dependent variables.
      The analyses indicated that Children's Depression Inventory (CDI) scores at the
      initial assessment predicted changes in mother-reported social competence from
      the initial assessment to the latter assessment. This study also examined the
      impact of an additional stressor, maternal HIV infection, on this same relation.
      The analyses indicated that maternal HIV infection did not moderate the relation
      between childhood self-reported depressive symptoms and later competence.

PMID- 14710471
TI  - Wave-front analysis as screening technique for amblyogenic ametropia with and
      without cycloplegia.
AB  - INTRODUCTION: For many years, attempts have been made to find an easy, efficient
      and inexpensive method to screen children for amblyogenic ametropia. Wave-front
      analysis is a new way to determine the refractive state of the eye from a
      distance. This technique could be a useful tool for infant screening. PURPOSE:
      The purpose of the study was the evaluation of the efficacy of a commercially
      available wave-front analyzing autorefractometer (SureSight, software version
      2.0, Welch Allyn, Skaneateles Falls, NY 13153, U.S.A.) in detecting amblyogenic
      ametropia in patients with and without cycloplegia. METHODS: 256 eyes (-28.25 D
      to +7.88 D spherical equivalent) of 128 patients (1-81 years) were examined with
      the wave-front autorefractometer under cycloplegia. Prior to this investigation,
      108 eyes (-21.38 D to 75 D) of 54 of these patients (1-76 years) were refracted
      without cycloplegia. The readings of the wave-front autorefractometer were
      compared with the results of retinoscopy under cycloplegia. RESULTS: Without
      cycloplegia, the sensitivity in detecting any amblyogenic ametropia such as
      anisometropia, astigmatism, myopia or hyperopia was 94%, while the specificity
      was 63%. Following cycloplegia, the sensitivity decreased to 87% and the
      specificity increased to 80%. CONCLUSION: Wave-front analyzing refractometry is
      highly applicable for infant screening. At the present state of development, the
      efficacy in detecting amblyogenic ametropia is similar to that of other screening
      techniques and instruments that operate from distance. Cycloplegia enhances the
      sensitivity in detecting hyperopia and decreases the sensitivity in detecting
      astigmatism.

PMID- 14710473
TI  - Bilateral Duane retraction syndrome associated with an extraordinary hand
      anomaly.
AB  - Duane retraction syndrome is an ocular motility disorder with which an increasing
      number of congenital abnormalities appear to be associated. In the present paper
      the authors report a case of bilateral Duane retraction syndrome with an
      extraordinary hand abnormality. Numerous theories concerning the etiology and
      pathogenesis of Duane retraction syndrome and its relationship to the associated
      findings have been proposed, but the exact mechanism is still under
      investigation. Further multi-centered studies and the classification of the
      associated clinical findings in an organized manner may help to explain this
      mechanism.

PMID- 14710472
TI  - Different levels of TIMPs and MMPs in human lateral and medial rectus muscle
      tissue excised from strabismic patients.
AB  - PURPOSE: To arrive at an understanding of the differences in gene and protein
      expression between human lateral and medial rectus muscle tissue excised from
      strabismic patients. METHODS: Resected fragments of the lateral and medial rectus
      muscles obtained during strabismus surgery were frozen under liquid nitrogen and
      pulverized by a Freezer/Mill system. Radiolabelled cDNA was synthesized from
      polyA+ RNA and hybridized with a gene array nylon membrane (Atlas Human 1.2
      Array) to detect the difference in gene expression between the lateral and medial
      rectus muscles. Based on the gene array results, tissue inhibitor of
      metalloproteinases (TIMP)-1 and 2, matrix metalloproteinase (MMP)-2, and bone
      morphogenetic protein (BMP)-4 were measured in solubilized muscle tissues by
      enzyme immunoassay and normalized by unit length of resection. RESULTS: The
      resected lateral rectus muscle had significantly smaller amounts of TIMP-1, TIMP
      2 and BMP-4 but larger amounts of MMP-2 compared to the medial rectus muscle (P <
      0.001, Mann-Whitney U test). The amounts of TIMP-1 in the muscle when the lateral
      and medial rectus were combined were positively correlated with TIMP-2 and BMP-4,
      while the amounts of TIMP-2 positively correlated with BMP-4 (P < 0.001, Spearman
      rank correlation test). The amounts of BMP-4 in both muscles increased
      significantly with age (P = 0.0003). CONCLUSIONS: Resected tissue from the
      lateral and medial rectus muscles had different levels of expression of TIMP-1
      and 2, MMP-2, and BMP-4. These molecular differences may underlie different
      characteristics of the two extraocular muscles and may also influence the process
      of wound healing after strabismus surgery.

PMID- 14710474
TI  - Strabismus following endoscopic orbital decompression for thyroid eye disease.
AB  - Endoscopic orbital decompression may be used to treat disfiguring proptosis or
      sight threatening optic nerve compression in patients with thyroid eye disease.
      Strabismus is common in thyroid eye disease and frequently follows decompression
      surgery. We retrospectively reviewed patients undergoing endoscopic decompression
      for thyroid eye disease, by a single surgeon, from 1994 to 2000. Twenty-three
      patients (21 female, 2 male) were identified with a mean age of 47.5 years. At
      presentation, 21 patients had proptosis, 8 optic nerve compression (2 without
      proptosis) and 11 strabismus (9 complained of diplopia) with a mean BSV score of
      24.5 before decompression. Forty orbits were decompressed with a mean decrease in
      proptosis of 3.3 mm. Following decompression, the mean BSV score was 25, and 17
      patients had manifest strabismus in primary gaze (3 at near only) of whom 10 had
      pre-existing strabismus. Five patients had new diplopia (22%). Eleven patients
      ultimately required strabismus surgery of whom 8 had manifest strabismus before
      decompression. Following strabismus surgery, the mean BSV score was 37. The final
      BSV score for those not requiring strabismus surgery was 29. Mean follow-up was
      28 months. Endoscopic orbital decompression can effectively treat disfiguring
      proptosis. Diplopia is a common complication, but pre-existing diplopia may
      improve.

PMID- 14710475
TI  - The incidence of strabismus and refractive error in patients with
      blepharophimosis, ptosis and epicanthus inversus syndrome (BPES).
AB  - A retrospective review was carried out of 204 patients with blepharophimosis,
      (blepharo) ptosis and epicanthus inversus syndrome (BPES). Of these, 94 (46%) had
      an autosomal dominant family history of BPES. Forty (20%) had manifest
      strabismus. Of these, 28 (70%) had esotropia, 10 (25%) had exotropia and 2 (5%)
      had hypertropia. Twelve (6%) patients had nystagmus. Seventy (34%) patients had a
      significant refractive error requiring spectacles. Twenty-one (30%) of these
      patients had anisometropic hypermetropia and 24 (34%) had anisometropic myopia.
      Forty-three patients had bilateral amblyopia and 40 had unilateral amblyopia,
      with 26 (65%) of these undergoing occlusion treatment. Of these, 14 had
      strabismus and refractive error, 7 refractive error only, 2 strabismus only and 3
      neither refractive error nor strabismus. We conclude that there is a higher
      incidence of strabismus and refractive error in patients with BPES than in the
      normal population.

PMID- 14710476
TI  - Outcome of ocular motility disturbances in orbital injuries.
AB  - AIMS: The purpose of this study was to retrospectively address the referral
      patterns of patients with orbital injuries presenting to the Orthoptic Clinic, to
      document the types of injury sustained and corresponding ocular motility defects,
      and to evaluate the eventual ocular motility outcome of these patients. METHODS:
      This study documented the findings of orthoptic and ophthalmic investigations,
      history of orbital injury and surgical details where applicable. Case notes of 30
      patients were reviewed, of which 22 had an orbital fracture and eight a soft
      tissue injury. The severity of injury, referral pattern to either maxillofacial
      or ophthalmology units, and age at time of injury were compared to eventual
      ocular motility outcome. RESULTS AND CONCLUSION: Despite there being more
      patients referred initially to the maxillofacial unit, there was no significant
      difference in outcome regardless of route of referral, type of injury or age at
      time of injury. The causes of injury included sports, assault, falls and road
      traffic accidents.

PMID- 14710477
TI  - [Possible consequences of subclinical hypothyroidism].
AB  - Subclinical hypothyroidism is defined as elevated TSH in the presence of normal
      free T4 and T3 levels. This review discusses the following questions concerning
      subclinical hypothyroidism that have not been solved yet: 1) does elevated TSH
      always mean failure of the thyroid gland? 2) Do patients with subclinical
      hypothyroidism always develop overt hypothyroidism? 3) Are they symptomatic? 4)
      Does treatment with L-Thyroxine cure these symptoms,--if they exist? Summarizing
      the results of the literature one can give the following answers: 1) Elevated TSH
      with normal free T4 can but does not necessarily mean thyroid failure. 2)
      Patients with positive thyroid antibodies and especially with TSH levels above 10
      mU/l are at high risk to develop overt hypothyroidism. 3) Typical symptoms
      (thyroid-specific, cardiovascular, neurological and psychiatric and finally
      alterations of risk factors for atherosclerosis) seem to occur in a greatly
      varying percentage of patients--some of the described symptoms are of
      questionable clinical importance. 4) Some of the symptoms, especially the
      cardiovascular, seem to be treatable by L-T4, whereas others like most of the
      changes in lipid metabolism can not be influenced by normalization of the TSH
      levels. In conclusion, screening for TSH and free T4 seems to be justified in
      elderly women, where the prevalence of the disease is approximately 20%. However,
      treatment of "symptoms" of subclinical hypothyroidism like elevated cholesterol
      levels or depression should be done only in patients with a TSH > 10 mU/l and
      there only with great caution in order to avoid unnecessary overdosage with the
      danger of eliciting atrial fibrillation.

PMID- 14710478
TI  - [Subclinical hyperthyroidism and atrial fibrillation].
AB  - Atrial fibrillation (AF), the most widespread arrhythmia, is a source of
      disability and death in the elderly, in particular because of the functional
      heart failure entailed and the considerable frequency of thromboembolic
      complications. Today, overt hyperthyroidism (oHT) is generally believed to be the
      most important extracardiogenic predisposition factor for AF. There exists no
      widespread acceptance so far that subclinical hyperthroidism (sHT) influences the
      occurrence of AF. Furthermore, there are no clear recommendations for treatment
      of sHT to prevent AF. Recent data confirm AF prevalence to be 5-6 times higher
      not only in cases of oHT but also in sHT patients compared with a reference group
      with normal thyroid function. Subclinical hyperthyroidism increases the
      prevalence of AF approximately to the same extent as oHT and has to be included
      in diagnostical considerations in patients with AF.

PMID- 14710479
TI  - [Hypothyroidism and the heart].
AB  - The cardiovascular system is sensitive to the action of thyroid hormones, and
      thyroid dysfunction causes a wide spectrum of cardiovascular changes. The effect
      of overt hypothyroidism on the cardiovascular system has long been recognised.
      Nowadays, the clinical presentation of cardiovascular symptoms related to
      hypothyroidism is only rarely observed due to early diagnosis of hypothyroidism
      by easily available thyroid-stimulating hormone assays. Overt hypothyroidism
      causes changes in such parameters of cardiovascular function as heart rate, left
      ventricular systolic and diastolic function, blood, arterial pressure and
      systemic vascular resistance. During the last years, there has been increasing
      evidence that subclinical hypothyroidism may also impair the cardiovascular
      system. This review discusses the effect of hypothyroidism on the cardiovascular
      system.

PMID- 14710481
TI  - [Significance of thyroid function in the treatment of sterility].
AB  - Latent subclinical hypothyroidism represents a particular problem in treatment
      for sterility, and can only be diagnosed after the results of a TRH test have
      been obtained (delta TSH > 15 microE/ml). Bearing these results in mind and by
      the administration of thyroid gland hormones or combinations of gonadotropins or
      clomifen, pregnancy rates in women with anovulatory sterility can be improved.

PMID- 14710480
TI  - [Value of intensive thyroid assessment in male infertility].
AB  - In infertile men thyroid hormone and antibody testing was performed and
      correlated with the results of semen analyses. Evaluation included semen
      analyses, physical examination, evaluation of sex steroid hormones, thyroid
      hormones (bTSH, fT4, fT3) and thyroid antibody testing (TGA, TPO-Ab, TRAK).
      Furthermore 45 men with normal thyroid function were scheduled for TRH testing.
      No one was diagnosed as having manifest hypo- or hyperthyroidism. Latent thyroid
      dysfunction had no effect on semen parameters. Elevated TPO-Ab were significantly
      correlated with reduction in motility of spermatozoa. The routine assessment of
      thyroid hormones and antibodies in infertile men is not recommended. Subclinical
      hypothyroidism as a result of TRH testing is a rare finding in infertile men.

PMID- 14710483
TI  - Nursing's message to the world. Interview by Marie Manthey.

PMID- 14710482
TI  - [Disorders of the thyroid gland in neonates and youth: latent hypothyroidism and
      hyperthyroidism].
AB  - Etiology and clinical manifestation of subclinical hypothyroidism is different in
      neonates and in young. In the neonatal period babies present with jaundice and/or
      constipation due to thyroid hypoplasia, thyroid ectopia or transient
      hypothyroidism. The main reason for subclinical hypothyroidism in the youth is
      Hashimoto thyroiditis. Indication for thyroxin therapy in subclinical
      hypothyroidism is discussed controversial in the literature. For best growing and
      maturation in childhood thyroxin therapy should be given. Subclinical
      hyperthyroidism is rare in childhood. The main reasons are Graves' disease or
      Hashimoto thyroiditis (initial period). The therapy of subclinical
      hyperthyroidism is the same as in overt hyperthyroidism.

PMID- 14710484
TI  - The leader as a voice coach. Interview by Beth Good.

PMID- 14710485
TI  - [Experiencing autonomy in the nursing home: an on site study].

PMID- 14710486
TI  - [Nursing, caring or compassion. A healing culture or interpersonal relations].

PMID- 14710487
TI  - [Intuition as the basis of effective interventions: trusting complex internal
      logic].

PMID- 14710488
TI  - [Competence in making nursing diagnoses: what computers cannot do].

PMID- 14710489
TI  - [Teaching concept for introduction of electronic data processing: adjusting to
      the needs and abilities of students].

PMID- 14710490
TI  - [East-West educational dialogue in nursing: "I wish for more uniformity"
      (interview by Katrin Balzer)].

PMID- 14710491
TI  - [Unit management in a primary nursing system: from unit mother to leadership
      role].

PMID- 14710492
TI  - [Developing a trusting relationship with the patient: a question of attitude].

PMID- 14710493
TI  - [Autonomy as the central value in nursing: freedom of choice].

PMID- 14710494
TI  - [Gray zone of patient mental competence: the path to autonomy via dialogue].

PMID- 14710495
TI  - [150 years subcutaneous injection: history of effectiveness and adverse effects].

PMID- 14710496
TI  - [The woman--not worth mentioning?].

PMID- 14710497
TI  - [From case to case: sleepless in....].

PMID- 14710498
TI  - [Stress prevention--also an educational topic: before it is too late].

PMID- 14710499
TI  - [Wound management, 12--Dressings for intravascular indwelling catheters: search
      for optimal nursing care--a never ending story?].

PMID- 14710500
TI  - ["Are you afraid?" Results of a study of communication between nurses and
      demented elderly patients].

PMID- 14710501
TI  - The bone and joint decade 2000-2010.

PMID- 14710502
TI  - The rise of osteoarthritis.

PMID- 14710503
TI  - The changing dimensions of rheumatoid arthritis and its treatment.

PMID- 14710504
TI  - Community wells to mitigate the arsenic crisis in Bangladesh.
AB  - OBJECTIVE: To monitor the effectiveness of deep community wells in reducing
      exposure to elevated levels of arsenic in groundwater pumped from shallower
      aquifers. METHODS: Six community wells ranging in depth from 60 m to 140 m were
      installed in villages where very few of the wells already present produced safe
      water. By means of flow meters and interviews with villagers carrying water from
      the community wells, a study was made of the extent to which these were used
      during one year. The results were compared with household and well data obtained
      during a previous survey in the same area. FINDINGS: The mean arsenic
      concentration in water pumped from wells already in use in the villages where the
      community wells, were installed was 180 +/- 140 micrograms/l (n = 956). Monthly
      sampling for 4-11 months showed that arsenic levels in groundwater from five of
      the six newly installed wells were consistently within the WHO guideline value of
      10 micrograms/l for drinking-water. One of these wells met the Bangladesh
      standard of 50 micrograms/l arsenic but failed to meet the WHO guideline values
      for manganese and uranium in drinking-water. The community wells were very
      popular. Many women walked hundreds of metres each day to fetch water from them.
      On average, 2200 litres were hand-pumped daily from each community well,
      regardless of the season. CONCLUSION: A single community well can meet the needs
      of some 500 people residing within a radius of 150 m of it in a densely populated
      village. Properly monitored community wells should become more prominent in
      campaigns to reduce arsenic exposure in Bangladesh. Between 8000 and 10,000 deep
      community wells are needed to provide safe water for the four to five million
      people living in the most severely affected parts of the country.

PMID- 14710505
TI  - Prevalence of reproductive tract infections, genital prolapse, and obesity in a
      rural community in Lebanon.
AB  - OBJECTIVE: To determine the prevalence of reproduction-related illnesses in a
      rural community in Lebanon. METHODS: Data were collected through interviews with
      women in their homes, physical examinations and history taking by physicians in a
      clinic in the community, and laboratory tests. A total of 557 ever-married women
      aged 15-60 years were selected randomly. FINDINGS: Just over half of the sample
      (268, 50.6%) had five or more children, and (320, 78.9%) of women aged < 45 years
      were using contraception. The prevalence of reproductive tract infections was
      very low: six (1.2%) women had sexually transmitted diseases and 47 (9.3%) had
      endogenous reproductive tract infections. None had chlamydial infection or a
      positive serological finding of syphilis. None had invasive cervical cancer, and
      only one had cervical dysplasia. In contrast, genital prolapse and gynaecological
      morbidity were elevated. Half of the women studied (251, 49.6%) had genital
      prolapse, and 153 (30.2%) were obese. CONCLUSION: The prevalence of reproductive
      tract infections in this conservative rural community in east Lebanon was low.
      Possible explanations include the conservative nature of the community, the high
      rate of utilization of health care services, and the liberal use of antibiotics
      without a prescription. More importantly, the study showed an unexpectedly high
      prevalence of genital prolapse and obesity--a finding that has clear implications
      for primary health care priorities in such rural communities.

PMID- 14710506
TI  - Burden of major musculoskeletal conditions.
AB  - Musculoskeletal conditions are a major burden on individuals, health systems, and
      social care systems, with indirect costs being predominant. This burden has been
      recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade
      2000-2010. This paper describes the burden of four major musculoskeletal
      conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back
      pain. Osteoarthritis, which is characterized by loss of joint cartilage that
      leads to pain and loss of function primarily in the knees and hips, affects 9.6%
      of men and 18% of women aged > 60 years. Increases in life expectancy and ageing
      populations are expected to make osteoarthritis the fourth leading cause of
      disability by the year 2020. Joint replacement surgery, where available, provides
      effective relief. Rheumatoid arthritis is an inflammatory condition that usually
      affects multiple joints. It affects 0.3-1.0% of the general population and is
      more prevalent among women and in developed countries. Persistent inflammation
      leads to joint destruction, but the disease can be controlled with drugs. The
      incidence may be on the decline, but the increase in the number of older people
      in some regions makes it difficult to estimate future prevalence. Osteoporosis,
      which is characterized by low bone mass and microarchitectural deterioration, is
      a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip
      fracture is the most detrimental fracture, being associated with 20% mortality
      and 50% permanent loss in function. Low back pain is the most prevalent of
      musculoskeletal conditions; it affects nearly everyone at some point in time and
      about 4-33% of the population at any given point. Cultural factors greatly
      influence the prevalence and prognosis of low back pain.

PMID- 14710507
TI  - New approaches to pharmacological treatment of osteoporosis.
AB  - Osteoporosis has been recognized as a major public health problem for less than
      two decades. The increasing incidence of fragility fractures, such as vertebral,
      hip, and wrist fractures, first became apparent from epidemiological studies in
      the early and mid-1980s, when effective treatment was virtually unavailable.
      Pharmacological therapies that effectively reduce the number of fractures by
      improving bone mass are now available widely in countries around the world. Most
      current agents inhibit bone loss by reducing bone resorption, but emerging
      therapies may increase bone mass by directly promoting bone formation--as is the
      case with parathyroid hormone. Current treatment alternatives include
      bisphosphonates, calcitonin, and selective estrogen receptor modulators, but
      sufficient calcium and vitamin D are a prerequisite. The availability of evidence
      based data that show reductions in the incidence of fractures of 30-50% during
      treatment has been a major step forward in the pharmacological prevention of
      fractures. With all agents, fracture reduction is most pronounced for vertebral
      fracture in high-risk individuals; alendronate and risedronate also may protect
      against hip fracture in the elderly. New approaches to pharmacological treatment
      will include further development of existing drugs, especially with regard to
      tolerance and frequency of dosing. New avenues for targeting the condition will
      emerge as our knowledge of the regulatory mechanisms of bone remodelling
      increases, although issues of tissue specificity may be difficult to solve. In
      the long term, information gained through knowledge of bone genetics may be used
      to adapt pharmacological treatments more precisely to each individual.

PMID- 14710508
TI  - Rehabilitation of landmine victims--the ultimate challenge.
AB  - Antipersonnel landmines are often used indiscriminately and frequently result in
      injury or death of non-combatants. In the last 65 years, over 110 million mines
      have been spread throughout the world into an estimated 70 countries. Landmine
      victims use a disproportionately high amount of medical resources; the vast
      majority of incidents occur in regions and countries without a sophisticated
      medical infrastructure and with limited resources, where rehabilitation is
      difficult in the best of circumstances. It is suggested that only a quarter of
      the patients with amputation secondary to landmines receive appropriate care.

PMID- 14710509
TI  - Low back pain.
AB  - Low back pain is a leading cause of disability. It occurs in similar proportions
      in all cultures, interferes with quality of life and work performance, and is the
      most common reason for medical consultations. Few cases of back pain are due to
      specific causes; most cases are non-specific. Acute back pain is the most common
      presentation and is usually self-limiting, lasting less than three months
      regardless of treatment. Chronic back pain is a more difficult problem, which
      often has strong psychological overlay: work dissatisfaction, boredom, and a
      generous compensation system contribute to it. Among the diagnoses offered for
      chronic pain is fibromyalgia, an urban condition (the diagnosis is not made in
      rural settings) that does not differ materially from other instances of
      widespread chronic pain. Although disc protrusions detected on X-ray are often
      blamed, they rarely are responsible for the pain, and surgery is seldom
      successful at alleviating it. No single treatment is superior to others; patients
      prefer manipulative therapy, but studies have not demonstrated that it has any
      superiority over others. A WHO Advisory Panel has defined common outcome measures
      to be used to judge the efficacy of treatments for studies.

PMID- 14710510
TI  - Improved education in musculoskeletal conditions is necessary for all doctors.
AB  - It is likely that everyone will, at some time, suffer from a problem related to
      the musculoskeletal system, ranging from a very common problem such as
      osteoarthritis or back pain to severely disabling limb trauma or rheumatoid
      arthritis. Many musculoskeletal problems are chronic conditions. The most common
      symptoms are pain and disability, with an impact not only on individuals' quality
      of life but also, importantly, on people's ability to earn a living and be
      independent. It has been estimated that one in four consultations in primary care
      is caused by problems of the musculoskeletal system and that these conditions may
      account for up to 60% of all disability pensions. In contrast, teaching at
      undergraduate and graduate levels--and the resulting competence and confidence of
      many doctors--do not reflect the impact of these conditions on individuals and
      society. Many medical students do not have any clinical training in assessing
      patients with bone and joint problems. Under the umbrella of the Bone and Joint
      Decade 2000-2010, experts from all parts of the world with an interest in
      teaching have developed recommendations for an undergraduate curriculum to
      improve the teaching of musculoskeletal conditions in medical schools. The goal
      for each medical school should be a course in musculoskeletal medicine
      concentrating on clinical assessment, common outpatient musculoskeletal problems
      and recognition of emergencies. Improving competency in the management of
      musculoskeletal problems within primary care settings through improved education
      is the next aim, but there are needs for improvement for all professionals and at
      all levels within the health care system.

PMID- 14710511
TI  - Road traffic injuries--a neglected pandemic.

PMID- 14710512
TI  - Recent developments and future research in the bone and joint decade 2000-2010.

PMID- 14710514
TI  - Osteoarthritis beginning with inflammation. Definitions and correlations. 1975.

PMID- 14710513
TI  - Inflammation as an important feature of osteoarthritis.

PMID- 14710515
TI  - Tobacco control begins to take hold in the Philippines.

PMID- 14710516
TI  - "Transformation" prescribed for mental health care in the USA.

PMID- 14710517
TI  - Polio eradication: 7 countries and US$ 210 million to go.

PMID- 14710518
TI  - India remobilizes against polio.

PMID- 14710519
TI  - [Energy cost of running during a specific transition in duathlon].
AB  - The aim of the present study was to investigate the variability of the energy
      cost of running (Cr) during a simulated duathlon performed in outdoor conditions
      by elite duathletes. This duathlon consisted of 5 km of running, 30 km of
      cycling, and 5 km of running. The main result was the lack of significant
      difference in Cr between the two running bouts (210 +/- 10 mL d'O2.km-1.kg-1 vs.
      217 +/- 10 mL d'O2.km-1.kg-1). This result is different from those observed
      during a triathlon, where an increase of energy cost of running bout has been
      reported. Furthermore, during a short-distance duathlon performed by well-trained
      subjects, none of the physiological (ventilation alteration, metabolic changes,
      or dehydration) or biomechanical factors that are classically evoked in triathlon
      research to explain Cr variability seem to be affected by the run-cycle-run
      transition. These results seem to minimize the negative effect of the cycle-to
      run transition during a short-duration event in well-trained subjects.

PMID- 14710520
TI  - [Catecholamine response to the Wingate test in untrained women].
AB  - Supramaximal exercises are well known to induce a severe stress on the adrenal
      medulla and nervous sympathetic system. This stress induces increased plasma
      catecholamines concentrations. The responses of catecholamines to supramaximal
      exercises in women are still not well characterized and have been studied mostly
      in trained subjects. Hence the aim of the present study was to evaluate plasma
      catecholamine responses to a Wingate test in young and untrained women (n = 6)
      and men (n = 7). Venous plasma catecholamine concentrations were determined by
      HPLC, at rest, at the end of the warm-up and of the exercise, and during recovery
      (5, 10, 20, and 30 mn). Our results failed to show any significant difference in
      resting catecholamine concentrations ([A]p: 0.41 +/- 0.05 vs. 0.45 +/- 0.05 nmol.
      L-1; [NA]p: 3.28 +/- 0.68 vs. 2.58 +/- 0.26 nmol.L-1), kinetics, and maximal
      plasma catecholamine concentrations (Amax: 4.47 +/- 1.08 vs. 3.31 +/- 0.63 nmol.L
      1; NAmax: 18.05 +/- 1.11 vs. 14.01 +/- 2.02 nmol.L-1) in response to the Wingate
      test between women and men, respectively. The Amax/NAmax ratio used as an index
      of adrenal medulla sensitivity to sympathetic input was also similar between
      genders. In conclusion, this study was able to demonstrate, in untrained
      subjects, that gender did not alder the sympatho-adrenergic response induced by a
      severe stress.

PMID- 14710521
TI  - Ambulatory activity and simple cardiorespiratory parameters at rest and
      submaximal exercise.
AB  - The purpose of this study was to explore the relationship between objectively
      determined ambulatory activity and simple cardiorespiratory parameters (heart
      rate and blood pressure at rest and during submaximal exercise) in individuals
      who were stratified for self-reported participation (yes/any vs. no/none) in
      vigorous physical activity (PA). Ninety-eight subjects (African Americans: 7 M,
      16 F; Caucasians: 33 M, 42 F; mean age 46.4 +/- 15.4 yrs; mean BMI 26.7 +/- 4.8)
      wore a pedometer for 21 consecutive days and completed a 10-min submaximal
      treadmill graded exercise test with HR (beats/min) and BP (mmHg) measured while
      walking at 4.8 km/hr and a 10% grade. Subjects averaged 7,618 +/- 3.045
      steps/day. There were no differences in steps/day by self-reported vigorous PA
      strata. There was an inverse relationship (r = -0.35, p = 0.03) between steps/day
      and resting HR in subjects who reported no vigorous PA. There was an inverse
      relationship (r = -0.22, p = 0.04) between steps/day and submaximal HR in all
      subjects. When stratified for self-reported vigorous PA, the inverse relationship
      between steps/day and submaximal HR was stronger for those reporting no vigorous
      PA (r = -0.39, p = 0.01) vs. those reporting any vigorous PA (r = -0.28, p =
      0.05). There was no relationship between steps/day and BP at rest or during
      exercise in this normotensive sample.

PMID- 14710522
TI  - Increase in serum S100B protein level after a swimming race.
AB  - Physical activity has been shown to be a beneficial stimulus to the central and
      peripheral nervous systems. The S100B is a cytokine physiologically produced and
      released predominantly by astrocytes on the central nervous system (CNS). In
      order to study the possible influence of a nonimpact exercise on S100B serum
      levels, we measured this protein serum level after a 7,600-meter swimming race.
      We observed an increase in S100B levels in athletes post-race compared with their
      baseline values, pointing to a potential acute influence of physical exercise on
      serum S100B levels not related with CNS injury. We discuss this result and
      emphasize the possible central and peripheral origins of S100B serum levels.

PMID- 14710523
TI  - [Effect of 4 weeks of training on the limit time at VO2 max].
AB  - The purpose of this study was to examine the effect of 4 weeks training in
      running on the time spent at VO2max (tlim VO2max). Eight athletes carried out,
      before and after an aerobic training, an incremental and five exhaustive tests at
      90, 95, 100, 115% vVO2max and at the critical power at VO2max (CV'; slope of the
      linear relation between the tlim VO2max and the distance limit at VO2max). This
      training did not significantly improve VO2max (p = 0.17) or tlim VO2max (p =
      0.72). However, the "tlim VO2max-intensity" curve was shifted toward the right,
      meaning that the athlete had to run at a higher intensity after training to
      obtain the same tlim VO2max. Tlim VO2max at CV' before training was significantly
      higher than tlim VO2max at 90, 95, 100, and 115% vVO2max (p < 0.05). This
      training increased CV' in absolute value (13.9 +/- 1.3 vs. 14.9 +/- 1.2 km.h-1, p
      < 0.05; n = 6) but not in relative value (86 +/- 4 vs. 86 +/- 5% vVO2max; p =
      0.9). In conclusion, in spite of the shift of the "tlim VO2max-intensity" curve,
      tlim VO2max was not significantly increased by this training. Furthermore, CV'
      allowed subjects to spend the longest time of exercise at VO2max during a
      continuous exercise with constant speed, but CV', expressed in % vVO2max, did not
      improve with this training.

PMID- 14710524
TI  - Potential interactions among vascular and muscular functional compartments during
      active hyperemia.
AB  - The increase in blood flow that accompanies the start of contractions (active
      hyperemia) is a complex phenomenon involving a fast phase in which blood flow
      increases quickly and then slows or decreases (seek phase) before stabilizing at
      a flow corresponding to the metabolic rate (matched phase). This pattern of blood
      flow change involves contributions from a flow-induced increase in flow, a
      response to short periods of occlusion or partial occlusion due to force
      generated by the muscle contraction, and metabolism. Even denervated, the
      vascular bed, which consists of endothelial cells, vascular smooth muscle cells,
      and an adventitial layer that has significant secretory potential, is able to
      coordinate the response pattern. Within the vascular wall, communication is
      possible bidirectionally across the wall and also along the wall in a retrograde
      or upstream direction. The signals involved, which range from endothelial cell
      products such as nitric oxide and endothelin to adenosine, a skeletal muscle
      metabolite, appear to be situation- and time-dependent. In addition to the
      communication potential within and along the vascular wall, signals from the
      vascular system are able to exert inotropic effects on mammalian skeletal muscle.

PMID- 14710525
TI  - Metabolic control of muscle blood flow during exercise in humans.
AB  - During muscle contraction, several mechanisms regulate blood flow to ensure a
      close coupling between muscle oxygen delivery and metabolic demand. No single
      factor has been identified to constitute the primary metabolic regulator, yet
      there are signal transduction pathways between skeletal muscle and the
      vasculature that induce vasodilation. A link between muscle metabolic events and
      microvascular control of blood flow is illustrated by local dilation of terminal
      arterioles during contraction of muscle fibers and conduction of vasodilation
      upstream. Endothelial-derived vasodilator mechanisms are known to exert control
      of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and
      endothelial-derived hyperpolarization factor (EDHF) are possible mediators of
      muscle vasodilation during exercise. In humans, adenosine has been shown to
      contribute to functional hyperemia as blood flow is reduced under nonselective
      adenosine-receptor blockade. No clear role has been demonstrated for either NO or
      PGI2(2), based on studies employing selective inhibition of these substances
      individually, suggesting a redundancy of vasodilator mechanisms. This is
      supported by recent work demonstrating that combined blockade of NOS and PGI2,
      and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans.
      Combined vasodilator blockade studies offer the potential to uncover important
      interactions and compensatory vasodilator responses. The signaling pathways that
      link metabolic events evoked by muscle contraction to vasodilatory signals in the
      local vascular bed remains an important area of study.

PMID- 14710526
TI  - Regulation of blood flow at the onset of exercise by feed forward and feedback
      mechanisms.
AB  - Blood flow adapts quickly after the onset of exercise to meet the metabolic
      demands of skeletal muscle. This review approaches the issue of how rapidly blood
      flow adapts and what the mechanisms for adaptation are primarily from a control
      theory perspective. Several recent papers have suggested that O2 transport
      proceeds at a rate that anticipates the metabolic demand over a very wide range
      of work rates. When considered from a control theory perspective, this implies
      involvement of feed forward control. Although there is one very important feed
      forward mechanism in the muscle pump that is activated with the onset of
      exercise, other evidence suggests that adjustment of blood flow to match the
      metabolic demand relies on feedback control from local dilator factors released
      in proportion to the metabolic demand. These distinct mechanisms with different
      onset times mean that blood flow adapts to the exercise demand with at least two
      distinct phases. The time course of the adaptation varies greatly between work
      rates, showing that blood flow control cannot be described by a linear control
      system and that the mechanisms responsible for vasodilation are dependent on work
      rate.

PMID- 14710527
TI  - [Disinhibition effects of benzodiazepines].

PMID- 14710528
TI  - [Medication-induced psychoses].

PMID- 14710529
TI  - [Experimental animal models of psychoses].

PMID- 14710530
TI  - [Drug abuse and schizophrenia: epidemiological data].

PMID- 14710531
TI  - [Schizophrenia and alcohol abuse: clinical data].

PMID- 14710532
TI  - [Schizophrenia and drug abuse: genetic aspects].

PMID- 14710533
TI  - [The effect of neuroleptics on the social behavior disorders of schizophrenic
      patients].

PMID- 14710534
TI  - [Therapeutic strategies in schizophrenic drug abuse].

PMID- 14710535
TI  - [From neuroleptics toward antipsychotics: psychopharmacology stand point].

PMID- 14710536
TI  - [From neuroleptics toward antipsychotics: practice of changing the treatment,
      choice of the time and disputes, clinical aspects].

PMID- 14710537
TI  - [From neuroleptics toward antipsychotics: quality of life and schizophrenia].

PMID- 14710539
TI  - Are more lumbar punctures needed after CT scan?

PMID- 14710538
TI  - Want to drastically cut LWBS numbers? Try ice packs and adding a fast track.
AB  - Your ED's left-without-being-seen (LWBS) rate is a direct reflection of quality
      of care and customer service, plus a high rate can put you at risk of charges
      that you are violating the Emergency Medical Treatment and Labor Act. Some simple
      strategies can help, but faster throughput is the ultimate solution. Handing out
      ice packs and other comfort items will help people wait longer. Announcing
      waiting times might help, but it can backfire. A dedicated minor emergency unit
      can reduce LWBS rates dramatically. One facility cut the rate from 14% to 2%.

PMID- 14710540
TI  - Tool ensures follow-up for traumatized children.

PMID- 14710541
TI  - 'Preflight checklist' builds safety culture, reduces nurse turnover.

PMID- 14710542
TI  - Risks to consider when planning a program for bariatric surgery.

PMID- 14710543
TI  - Study on RN education stirs controversy.

PMID- 14710544
TI  - Evolving role of the specialty coordinator.

PMID- 14710545
TI  - Frequent questions on OR fire safety.

PMID- 14710546
TI  - Planning a family visit program for PACU.
AB  - Hospitals can develop or improve a PACU visitation program by establishing a
      policy, setting rules for visitation, ensuring patient privacy, educating staff
      and families, and performing quality control. Resistance from nursing staff is
      fairly easy to overcome, and visitation in the PACU for all patients seems likely
      to become standard practice. Sullivan warns that not allowing visitation may be
      detrimental: "If you don't have a visitor program, you'll probably have people
      somehow figuring out what your phone number is, lurking outside the door, and
      trying to see if they can get in." She is confident that "if you have a good
      program that meets the needs of the patient, the family, and the nurse, it will
      be successful." PACU visitarion is integral to patient care and consistent with
      regulations such as those of the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO). Jeran explains: "As nurses, we're taught to believe in
      family-centered care. That's the way nursing programs are set up; that's what
      JCAHO wants. I think it's unacceptable to have an area [in the hospital] where
      you don't reunite the family, even if it's just for a few minutes. She adds,
      "Anything that's going to make the patient and family more comfortable as they go
      through a very stressful period needs to be instituted, and we just have to
      figure out a way to make it work for everyone."

PMID- 14710547
TI  - GAO report fills in picture of niche hospitals.

PMID- 14710548
TI  - Professional aspirations. From bedside helpers to certified long-term care
      experts, the nation's caregivers have come into their own.

PMID- 14710549
TI  - Comforting changes. In 25 years, long term care equipment has advanced to make
      residents' and caregivers' lives more comfortable.

PMID- 14710550
TI  - Breaking with tradition. Long-term care facilities have moved from sterile and
      foreboding to homes away from home.

PMID- 14710551
TI  - Histories of associations. American Association of Homes and Services for the
      Aging.

PMID- 14710552
TI  - Selling medicine.

PMID- 14710553
TI  - Medication errors: protecting both patient and provider.
AB  - Administering the right medication in the right dose via the right route to the
      right patient is essential to quality patient care. Providers must be educated on
      all related policies and periodically reviewed. In addition, providers must take
      personal responsibility to assure knowledge and ability to determine the correct
      medication in any given scenario and calculate the correct dose. EMS
      administrators, employers, providers and medical directors must work together to
      identify system problems and establish policies and procedures for efficient and
      effective prevention of medication errors. Until next time, be safe!.

PMID- 14710557
TI  - Beyond the debriefing debate: what should we be doing?
AB  - It is clear that it is very difficult to treat trauma-related stress after the
      fact. EMS and fire personnel must develop personal stress management strategies
      and have a personal-support system in place. Most stresses in EMS are the day-to
      day hassles of the job. Occasionally, some of us will be involved in a disaster
      operation. As with the day-to-day stressors, the best way to manage disasters is
      through planning and preparation. As Lauren Simon Ostrow wrote, "In the end, EMS
      may want to re-examine the all-American notion that we should always feel good,
      that stress is bad and that we have to take corrective action to resolve every
      negative reaction to stress, even if it is normal."

PMID- 14710558
TI  - Acute renal failure.

PMID- 14710560
TI  - Joint Commission examines the issue of organ donation.

PMID- 14710561
TI  - JCAHO joins organ donation breakthrough collaborative.

PMID- 14710562
TI  - 2004 changes for assisted living, critical access hospitals, health care
      networks, office-based surgery, and preferred provider organizations.

PMID- 14710563
TI  - National Patient Safety Goal on abbreviations clarified, implementation revised.

PMID- 14710564
TI  - Paediatric dentistry in the new millennium: 6. Dental anomalies in children.
AB  - Developmental defects of the human dentition are not uncommon and can adversely
      affect the physical and psychological health of children. This paper reviews
      briefly the most common dental defects that can occur during childhood and
      discusses in more detail defects of enamel and dentine. Guidelines are provided
      for clinicians to identify children who deviate from normal dental development in
      order to provide appropriate interventions or make appropriate referrals.

PMID- 14710565
TI  - Clinical governance in primary dental care--getting started.
AB  - Clinical Governance is a contractual requirement of everyone working in the NHS.
      This article explores the components, standards and key stages in developing
      effective clinical governance in primary dental care and the issues associated
      with quality assurance.

PMID- 14710566
TI  - Pathological migration: an unusual cause of midline diastema.
AB  - A 34-year-old female attended the orthodontic department and was concerned with a
      midline diastema in the lower arch. The diagnosis made was pathological migration
      owing to the habitual placement of her tongue stud on the incisal edges of her
      mandibular central incisors, forcing them apart. This article describes the
      causes of pathological migration, and other possible complications due to oral
      piercings.

PMID- 14710567
TI  - Use of tooth-coloured restorations in the management of toothwear.
AB  - The problem of toothwear appears to be increasing in both children and adults.
      Recent developments in bonding and aesthetic restorations have added to the
      dentist's armamentarium for restoring worn teeth. Bonded ceramic and composite
      restorations offer the possibility of conservative restoration of teeth already
      damaged by toothwear. Despite this, concern still remains regarding the
      durability and clinical performance of these restorations. This paper reviews the
      currently available techniques for providing tooth-coloured restorations in
      toothwear cases.

PMID- 14710568
TI  - Marsupialization of a large unilateral mandibular dentigerous cyst in a 6-year
      old boy--a case report.
AB  - This paper describes the case of a 6-year-old boy who presented with an
      asymptomatic large unilateral dentigerous cyst related to an unerupted 6. It was
      marsupialized under general anaesthetic, and subsequently resolved rapidly. The
      pathogenesis and aetiology of dentigerous cysts is discussed, together with
      alternative treatment modalities. This paper illustrates that a conservative
      surgical approach to the management of a dentigerous cyst in a child can be very
      successful. By preserving the associated permanent tooth, marsupialization
      minimizes any disruption to future dental development.

PMID- 14710569
TI  - The restorative management of hypodontia with implants: I. Overview of
      alternative treatment options.
AB  - The first part of this paper discusses the clinical features of patients with
      hypodontia. Medical, social and clinical factors must be taken into account,
      along with risks and benefits, before a treatment plan can be recommended and
      implemented for a patient. An overview of treatment options are considered with
      examples. In the second part, implant treatment options will be discussed in
      detail.

PMID- 14710570
TI  - Revisiting the role of dentists in prescribing antibiotics.
AB  - The purpose of this paper is to review the principles of therapeutic and
      prophylactic prescribing in light of the increasing problem of antibiotic
      resistance and the evidence of inappropriate use of antibiotics in dentistry.
      Recommendations based on a review of the evidence and good practice for
      prescribing therapeutic and prophylactic antibiotics will be given.

PMID- 14710571
TI  - Dentistry in the Armed Forces.
AB  - This paper describes the way dentistry is practiced in the Armed Forces and
      highlights the differences with civilian practice, especially during military
      operations. The military lifestyle is discussed and the various training pathways
      and career options available to Armed Forces dentists are outlined.

PMID- 14710572
TI  - Physical signs for the general dental practitioner. Case 10. CREST syndrome.

PMID- 14710573
TI  - [Psoriasis: a current disease].

PMID- 14710574
TI  - [Epidemiology and genetics of psoriasis].

PMID- 14710575
TI  - [Physiopathology of psoriasis].

PMID- 14710576
TI  - [How to evaluate the severity of psoriasis?].

PMID- 14710577
TI  - [Scores and indexes for evaluation psoriasis].

PMID- 14710578
TI  - [Questions to ask the patient in order to know his/her disease. The somatic
      context].

PMID- 14710579
TI  - [Questions to ask the patient in order to know his/her disease. The point of view
      of the patient].

PMID- 14710580
TI  - [Questions to ask the patient in order to know his/her disease. The psychologic
      context].

PMID- 14710581
TI  - [Psoriasis: do current treatments respond to all situations in practice?].

PMID- 14710582
TI  - [Near or far-off therapeutic perspectives].

PMID- 14710583
TI  - The study with a million women (and hopefully fewer mistakes).

PMID- 14710584
TI  - Hormone replacement therapy in climacteric and aging brain.

PMID- 14710585
TI  - The effect of polycystic ovary syndrome on health-related quality of life.
AB  - This article reviews current literature regarding polycystic ovary syndrome
      (PCOS) and health-related quality of life (HRQoL), as well as examining how some
      of the manifestations of PCOS affect HRQoL. The only quantitative study was
      performed in adolescent girls. It used a well-validated instrument and showed
      that HRQol was worse in those with PCOS in the areas of general health
      perceptions, behavior, physical functioning and family activity. No comparable
      study exists for adults with PCOS. However, qualitative psychological studies
      have demonstrated higher levels of depression, psychological and psychosexual
      morbidity and an increased response to stress in women with PCOS compared with
      controls. Low self-esteem, decreased social activity and less romantic
      contentment were reported in women with PCOS. Weight and hirsutism consistently
      caused more concern than menstrual problems or infertility. The symptoms
      associated with PCOS, namely hirsutism, acne, diabetes mellitus and obstructive
      sleep apnea syndrome (OSAS) were all reported to reduce HRQoL in separate
      studies. Encouragingly, treatment for acne and OSAS improved the HRQoL, although
      treatment for hirsutism did not. Quantitative studies on the effect of PCOS on
      HRQoL and the benefit of treatments need to be conducted.

PMID- 14710586
TI  - Insulin resistance and lipid profile in women with polycystic appearing ovaries:
      implications with regard to polycystic ovary syndrome.
AB  - The aim of this study was to investigate carbohydrate and lipid profiles in women
      with polycystic appearing ovaries (PCO) on ultrasound examination who did not
      fulfill the criteria for polycystic ovary syndrome (PCOS). We sonographically
      evaluated and biochemically diagnosed 35 patients with PCO, 31 women with PCOS
      and 23 healthy controls. We performed oral glucose tolerance tests (OGTT) and
      calculated the quantitative insulin sensitivity check index (QUICKI) and the
      homeostatic model assessment (HOMAIR) scores. Serum fasting insulin levels, 1-h
      insulin response, HOMAIR and QUICKI scores were significantly higher in the PCO
      and PCOS groups than in the controls. However, serum fasting glucose levels,
      fasting insulin levels, HOMAIR and QUICKI scores were similar in women with PCO
      and PCOS. In women with PCO, high-density lipoprotein (HDL) levels were higher,
      and very-low-density lipoprotein (VLDL) and triglyceride levels were lower
      compared with women with PCOS. Furthermore, insulin responses to OGTT, HOMAIR and
      QUICKI scores and lipid values correlated with serum androgen levels and body
      mass index (BMI) in PCO patients. In conclusion, women with PCO who do not
      fulfill the criteria for PCOS have abnormal insulin sensitivity and insulin
      resistance. The finding of similar insulin abnormalities in women with PCO to
      those in women with PCOS confirms that women with PCO have similar metabolic
      characteristics to those with PCOS.

PMID- 14710587
TI  - A prospective randomized controlled study of the effect of short coincubation of
      gametes during insemination on zona pellucida thickness.
AB  - A prospective, randomized study was conducted to evaluate the thickness, of zona
      pellucida (ZP) after brief or standard exposure of human oocytes to spermatozoa,
      and to determine the correlation between ZP thickness, fertilization rate and
      embryo quality. The mean ZP thickness 48 h after insemination was found to be
      significantly less in fertilized oocytes than in non-fertilized oocytes in all
      treated groups (13.72 +/- 3.0 microns and 15.08 +/- 2.5 microns, respectively; p
      < 0.007). Zona pellucida thickness correlated positively with embryo quality.
      Brief exposure of gametes was found to influence ZP thickness. The ZP was
      significantly thinner after brief and intracytoplasmic sperm injection (ICSI)
      exposure of oocytes to spermatozoa than after standard in vitro fertilization
      (IVF). The mean ZP thickness 24 and 48 h after fertilization was significantly
      greater in standard IVF (16.43 +/- 2.8 microns and 15.22 +/- 2.7 microns,
      respectively) than in either the brief exposure or ICSI groups (12.78 +/- 2.4
      microns and 13.01 +/- 3.5 microns vs. 13.46 +/- 2.2 microns and 13.16 +/- 2.4
      microns; p < 0.0001).

PMID- 14710588
TI  - Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent.
AB  - Endometrial cancer and hyperplasia have long been associated with diabetes.
      Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may
      inhibit the effect of progestogen therapy. This case report describes the
      treatment of a patient with atypical endometrial hyperplasia with an insulin
      sensitizing agent. A 37-year-old patient presented after failed treatment of
      endometrial hyperplasia with progestogen therapy. One month after initiating
      metformin therapy the patient's endometrial biopsy demonstrated proliferative
      endometrium. This patient's atypical endometrial hyperplasia regressed after the
      initiation of treatment with an insulin-sensitizing agent. This relatively new
      class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.

PMID- 14710589
TI  - Body mass index influences plasma concentration of neuropeptide Y in healthy
      female volunteers: a pilot study.
AB  - Neuropeptide Y (NPY) was measured in plasma obtained from healthy female
      volunteers twice in the natural menstrual cycle or the hormonal cycle caused by
      oral contraceptives about 2 weeks apart. The ratio between the NPY plasma
      concentration in the second sample and the first sample was influenced negatively
      by body mass index (BMI). There were no differences in NPY plasma concentrations
      on comparing the first and second samples. Age and the use or non-use of oral
      contraceptives did not exert any influence. BMI might be a confounding factor
      when determining NPY in the plasma of healthy women.

PMID- 14710590
TI  - Prevalence of thyroid disorders in pregnant women with mild iodine deficiency.
AB  - To assess the prevalence of thyroid disorders in a region with mild iodine
      deficiency, this study was undertaken in a randomized sample of pregnant women
      during different gestational periods. Evaluations were performed in 215 women:
      thyroid ultrasound scanning, thyroid stimulating hormone (TSH), free thyroxine
      (T4) and thyroid peroxidase (TPO) antibodies. At the time of participation in the
      study, some women (90/215) had been receiving 150-200 micrograms iodine.
      Hypothyroidism was found in four women (1.86%). Positive TPO antibodies were seen
      in 34 of 215 women (15.8%), and TPO antibody level over 150 mU/l was found in
      9.8% (21/215). There was no significant difference between TSH levels in women
      with positive or negative TPO antibodies. There were no differences in TSH level
      between the women receiving and those not receiving iodine prophylaxis. The
      prevalence of goiter in 211 euthyroid women was found to be 24.2% (51/211). in
      the group with iodine prophylaxis, thyroid volume was found to be significantly
      lower (t = 2.5; p = 0.02) than in women who had not received it, or had started
      it during the second trimester. By comparison of history data on the prevalence
      of aborted pregnancy between the group with positive (26.5%; 9/34) and the group
      with negative TPO antibodies (14.3%; 26/181), no significant differences were
      found. We conclude that, in mild iodine deficiency, pregnancy is related to a
      high risk of goiter, which can be prevented by iodine prophylaxis. TPO antibody
      carrier status in pregnant women is probably not associated with a significant
      risk of thyroid dysfunction or spontaneous abortion.

PMID- 14710592
TI  - Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule.
AB  - Ovarian steroids are important modulators of normal cell growth and
      differentiation as well as of carcinogenesis. External stimuli trigger cell
      surface receptors, resulting in activation of central signal transduction
      pathways, that are mediated by members of the mitogen-activated protein kinase
      (MAPK) family. These in turn, indirectly regulate cellular functions such as cell
      proliferation, cell cycle, and maintenance of malignant phenotype. In our in
      vitro study, we have investigated the effects of two synthetic estrogens on ERK 2
      activation. Estrogen receptor positive cells were incubated with the synthetic
      estrogens, ethinylestradiol (10(-9) mol/l) and 17 beta-estradiol valerate (10(-9)
      mol/l), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen 17 beta
      estradiol (10(-9) mol/l), for 5 min. The same experiments were repeated prior to
      preincubation with the antiestrogen ICI 182780. ERK 2 or the active form alone
      were detected by immunoblotting. A cell proliferation assay was used to study the
      response of cells to various treatments. Time kinetics were performed to study
      duration of kinase activated state. Cell incubation with EGF as well as with
      either natural or synthetic estrogen stimulated proliferation. ICI 182780
      inhibited this effect, but only in the case of estrogen. Synthetic estrogens
      activated MAP kinase in a time-dependent fashion, similar to 17 beta-estradiol.
      The estrogen receptor antagonist ICI 182780 blocked this effect. EGF induced a
      more pronounced and prolonged activation, even in the presence of the
      antiestrogen. Ethinylestradiol as used in oral contraceptives, and 17 beta
      estradiol and 17 beta-estradiol valerate as used in hormone replacement therapy,
      are able to activate MAP kinase. This activation was blocked by an antiestrogen.

PMID- 14710591
TI  - Low-dose (2.5 mg/day) finasteride treatment in hirsutism.
AB  - This study was performed to confirm the therapeutic effects of low-dose, (2.5
      mg/day) finasteride in hirsute women. Our study was a non-randomized prospective
      clinical trial. Twenty-nine patients with hirustism were included in the study.
      The patients received 2.5 mg finasteride once a day over a period of 12 months.
      Follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin,
      17 alpha-hydroxyprogesterone, estradiol, androstenedione, total and free
      testosterone, dehydroepiandrosterone sulfate levels and hirsutism scores were
      determined in all patients before treatment and at every 6 months during the
      therapy. The hirsutism score decreased from a mean of 18.4 +/- 4.6 to 8.4 +/- 4.2
      during the study. The per cent reduction in hirsutism score (mean +/- SD) at 6
      and 12 months was 29.2 +/- 14.5 and 55.7 +/- 14.9%, respectively. There were no
      significant differences in any of the hormone levels and no serious side-effects
      were observed during the treatment. In conclusion, low-dose finasteride (2.5
      mg/day) is a cost-effective, well-tolerated therapeutic agent without significant
      abnormal biochemical findings and can be used in place of high-dose (5 mg/day)
      finasteride in the treatment of hirsutism.

PMID- 14710593
TI  - 46, XY agonadism associated with adrenal adenoma/myelolipoma: report of a case
      analyzing Y-chromosome-specific sequences.
AB  - A unique patient with 46, XY agonadism associated with adrenal
      adenoma/myelolipoma is described. The patient was an 18-year-old female with
      primary amenorrhea, lack of secondary sexual development and an aldosterone
      producing adrenocortical adenoma associated with foci of myelolipoma. Molecular
      analyses of Y-chromosome-specific regions, including automated sequencing of the
      entire coding region of SRY, the Y-linked testis-determining gene, were
      performed. Our results excluded the possibility that a mutation in SRY was
      responsible for this unusual clinical combination.

PMID- 14710594
TI  - Reproductive abnormalities, teratogenicity, and developmental problems in
      American kestrels (Falco sparverius) exposed to polychlorinated biphenyls.
AB  - This study found abnormalities in multiple reproductive stages in captive
      American kestrels (Falco sparverius) when exposed to polychlorinated biphenyls
      (PCBs) through dietary and in ovo exposure. American kestrels laid eggs with
      environmentally relevant total PCB levels (34.1 micrograms/g whole egg wet
      weight) when consuming PCB-spiked (Aroclor 1248:1254:1260) food (5-7 micrograms/g
      body weight per day) for 100 d only in 1998. In 1999, the same adults laid eggs
      with estimated total PCBs of 23 micrograms/g. Effects of maternal (only female
      exposed) and paternal (only male exposed) in ovo PCB exposure were investigated.
      Maternal F1 eggs contained predicted total PCB concentrations of 0.34
      microgram/g. Specific abnormalities occurred more frequently during dietary F0
      exposure, particularly aggressive courtship interactions, clutch abandonment,
      occurrences of cracked eggs, and developmental effects. Multiple developmental
      effects were more pronounced during than after dietary PCB exposure of adults,
      and although these effects were limited, nevertheless they occurred in the F1
      maternal and F1 paternal pairs. However, the incidence of multiple deformities
      throughout the breeding season increased dramatically from 1998 (13%) to 1999
      (56%) in F0 PCB-exposed pairs. Developmental abnormalities were unlikely to be
      attributed to the extrinsic factors of disease, genetics, or nutritional (vitamin
      D3) deficiencies, but rather to adverse changes in parental behavior and
      intrinsic factors involving altered genetic material and PCB exposure. Readily
      cleared PCB congeners may induce specific types of behavioral and developmental
      abnormalities, but persistent congeners and metabolites are likely producing (1)
      odd laying patterns, (2) odd laying patterns, (2) developmental effects including
      embryonic underdevelopment and edema, and (3) increased incidences of multiple
      deformities within a clutch.

PMID- 14710595
TI  - Comparative susceptibility of B cells with different lineages to cytotoxicity and
      apoptosis induction by translational inhibitors.
AB  - The trichothecene mycotoxins, Shiga toxins (STs), and ricin are potent
      translational inhibitors that exert diverse mechanisms of action but all have the
      capacity to induce death by apoptosis. Germinal centers containing actively
      dividing B cells are particularly sensitive to protein synthesis inhibition, and,
      of these, the immature B cell is reportedly most susceptible to apoptosis. The
      objective of this study was to test the hypothesis that immature and mature B
      cell lineages were differentially susceptible to apoptosis and cytotoxicity
      induction by representative trichothecene mycotoxins, ST-1, and ricin, as well as
      cycloheximide (CHX), a prototypical protein synthesis inhibitor commonly used to
      study cell signal transduction. WEHI-231 and CH31 cells were used as
      representatives of phenotypically immature B cells, whereas CH12.LX cells were
      used to model mature B cells. Resultant data suggest that Type D and Type A
      trichothecenes, ricin, and ST-1 were more potent inducers of apoptosis than CHX,
      whereas Type B and Type A trichothecene metabolites were less. CHX and the
      trichothecenes affected immature and mature B cells equally, thus suggesting that
      toxicity due to these natural toxins was lineage independent. In contrast, mature
      B cells were more sensitive to ricin- and ST-1-induced cytotoxicity and apoptosis
      than immature B cells. Taken together, these results suggest that B cells are
      targets of a diverse array of naturally occurring translational inhibitors.
      Upregulation of apoptosis in B lymphocytes may contribute to the impairment of
      the immune response and other symptoms described following exposure to these
      toxins.

PMID- 14710597
TI  - Pharmacokinetics/pharmacodynamics (PK/PD) modeling of risks of kidney toxicity
      from exposure to cadmium: estimates of dietary risks in the U.S. population.
AB  - An analysis of epidemiological studies of associations between exposure to
      cadmium and kidney toxicity was conducted. Dose-response functions relating low
      molecular-weight (LMW) proteinuria to various indices of cadmium dose (dietary
      cadmium intake, urinary cadmium excretion, or tissue cadmium burden) were
      obtained from 15 studies of diverse exposures (occupational, general
      environmental, environmental contamination). Estimates of the dose corresponding
      to probabilities of LMW proteinuria of 0.1, 0.15, or 0.2 were transformed from
      the reported dose units into corresponding estimates of target organ dose
      (microgram Cd/g renal cortex, RC) by simulation using a pharmacokinetics (PK)
      model. The median RC associated with a 0.1 probability (RC10M) of LMW proteinuria
      was predicted to be 153 micrograms Cd/g cortex (95% confidence interval [CI]: 84
      263). The lower confidence limit on the RC10M (RC10L, 84 micrograms/g cortex) was
      predicted to be attained with a constant chronic intake of 1 microgram/kg/d in
      females or 2.2 micrograms/kg/d in males. The RC10L was 2.5-5 times higher than
      the median RCs predicted to result from dietary cadmium intake in U.S. nonsmokers
      (microgram Cd/g cortex: 33, females; 17, males) and 1.6-3 times higher than the
      corresponding 95th percentile RCs (53, females; 27, males). Additional exposure
      from smoking cigarettes (approximately 20 cigarettes/d, 3 micrograms Cd
      inhaled/d) was predicted to increase the median RC (microgram/g cortex) by
      approximately 45-70% (48, females; 29, males); however, predicted 95th percentile
      RCs for smokers (66, females; 38, males) were lower than the RC10L. These results
      indicate that, for most of the U.S. population, dietary-derived risks are likely
      to be negligible, in the absence of exposures from other sources.

PMID- 14710596
TI  - Organochlorines affect the major androgenic hormone, testosterone, in male polar
      bears (Ursus maritimus) at Svalbard.
AB  - Normal sexual development and subsequent reproductive function are dependent on
      appropriate testosterone production and action. The regulation of steroid
      hormones, including androgens, can be influenced by both biological and
      environmental factors, including environmental chemicals. Concentrations of
      organochlorines are considerably greater in Svalbard polar bears than in polar
      bears from other regions. Between 1995 and 1998, samples were collected from 121
      male polar bears (Ursus maritimus) from the Svalbard area. In this study,
      testosterone concentration variations were described for male polar bears during
      different seasons and for all age groups. To study possible relationships between
      plasma testosterone concentrations and biological factors, such as age, axial
      girth, and extractable plasma fat, and organochlorine contaminants including
      hexachlorocyclohexanes, hexachlorobenzene, chlordanes, p,p'-DDE, and 16
      individual polychlorinated biphenyl (PCB) congeners, identical statistical
      analyses were performed on the total population and a subsample of reproductively
      active adults. Of the biological factors, axial girth showed a significant
      positive relationship and percentage extractable fat and a significant negative
      relationship with the testosterone concentrations. Both the epsilon pesticides
      and epsilon PCBs made significant negative contributions to the variation of the
      plasma testosterone concentration. The continuous presence of high concentrations
      of organochlorines in male polar bears throughout their life could possibly
      aggravate any reproductive toxicity that may have occurred during fetal and early
      postnatal development.

PMID- 14710599
TI  - [Relearning astonishment].

PMID- 14710598
TI  - Dioxin, dibenzofuran, and polychlorinated biphenyl (PCB) levels in food from
      Agent Orange-sprayed and nonsprayed areas of Laos.
AB  - During the Vietnam War, a phenoxy-herbicide mixture called Agent Orange, which
      was contaminated with 2,3,7,8-tetrachlorodibenzodioxin, or TCDD, was used
      primarily for destruction of forest and other foliage in order to prevent enemy
      troop movement and protect American and allied troops and military bases in the
      south of Vietnam. Smaller areas of Laos and Cambodia were also sprayed with Agent
      Orange between 1962 and 1971 from fixed-wing aircraft. In 2001, 28 food samples
      consisting of meat, fish, and dairy products were collected in sprayed and
      nonsprayed areas of Laos and analyzed for dioxins, dioxinlike dibenzofurans, and
      selected polychlorinated biphenyl (PCB) congeners by high-resolution gas
      chromatography/high-resolution mass spectrometry at laboratories in Germany and
      Canada. Low levels of dioxin and other dioxinlike substances were found in
      Laotian food, similar to levels present in recent exported Vietnamese food to
      United States. Vietnam is geographically adjacent to Laos. Total dioxin toxic
      equivalent (TEQ) levels were similar in samples from sprayed and non-sprayed
      areas, ranging from 0.009 to 0.851 pg/g or parts per trillion (ppt) in sprayed
      Sepone, and from 0.022 to 0.537 pg/g or ppt wet weight in non sprayed Vientiane.
      However, the Laotian fish samples from the Agent Orange-sprayed area had, on
      average, a higher proportion of total TEQ from TCDD (31.7% vs. 9.4%) compared to
      the nonsprayed area. Some other food items, duck eggs and pork liver from Sepone,
      also had severalfold higher TCDD levels than similar food samples from Vientiane,
      0.029 vs. 0.011 pg/g and 0.070 vs. 0.004 pg/g wet weight, respectively. There
      were no substantial differences in levels of dibenzofuran and PCB congeners. In
      general, elevated TCDD levels were not found in Laotian food samples. It is
      possible that dioxin-contaminated areas, or "hot spots," exist in Laos as they do
      in Vietnam, although they have not yet been identified.

PMID- 14710600
TI  - [Quality of life. Nursing care in the tempo of dementia].

PMID- 14710601
TI  - [Symptoms of dementia. Fear of memory loss].

PMID- 14710602
TI  - [Information and communication technology. Patient--electronically connected].

PMID- 14710603
TI  - [Work organization. 12-hour shift--a model with question marks].

PMID- 14710604
TI  - [Frankfurt Book Exhibit. Multitude of new publications].

PMID- 14710605
TI  - [Independent, but sweet].

PMID- 14710606
TI  - [Basic and graduate education becomes concrete].

PMID- 14710607
TI  - [Resolutely yes!].

PMID- 14710608
TI  - [Benevolent nursing care at home. The precious nursing of family caregivers].

PMID- 14710609
TI  - [Psychiatric nursing in an open milieu. Lost values in routine nursing care].

PMID- 14710610
TI  - [Standards of care in anesthesia. Quality guarantee in the operating room].

PMID- 14710611
TI  - [Aromatherapy improves well being in EMS. Orange, lavender or pine?].

PMID- 14710612
TI  - ["Knowing to take time for the patient" (interview by Francoise Taillens)].

PMID- 14710614
TI  - [Development of cariology. Introduction].

PMID- 14710615
TI  - [Caries diagnosis: the lesions are central].
AB  - In this paper two new visual scoring systems are described, aimed at estimating
      both depth and activity of occlusal lesions. Their validity is acceptable for
      lesion depth estimation. However, the validity of the activity estimate is to be
      questioned. Both for approximal enamel and dentine lesions as for deep dentinal
      occlusal lesions, bite-wing radiographs are still useful for evaluation of new
      lesions and lesion progression. Many quantitative caries diagnostic methods are
      being developed, but to this date none of them has been shown to be reliably
      applicable in lesion monitoring. The evaluation of caries risk factors is
      primarily useful for selecting preventive treatment options. Other caries
      prediction-tests than those based on the present caries lesions are of little
      value. The main disadvantage of such prediction models is that they are usually
      limited to application in children, where caries is a disease that affects all
      ages.

PMID- 14710616
TI  - [Decision making in cariology].
AB  - By conducting an oral examination, during radiographic examination and in
      treatment planning procedures dentists make numerous decisions. A dentist will be
      required to make his decisions explicit. Decision trees and decision analyses may
      play an important role. In a decision analysis, the probability of correct and
      incorrect decisions are multiplied by the utility of the decision outcomes. The
      treatment outcome with the highest expected utility should be selected. Complex
      decision tasks such as the estimation of an individual's caries risk or the
      diagnosis of bone disorders are currently available as computer applications.
      Also, a preliminary version of a computer programme which detects caries lesions
      from bitewing radiographs independent from the dentist has become available. It
      is expected that the applicability of decision analyses will increase when
      implemented in the dental practice software packages.

PMID- 14710617
TI  - [Routine dental examination as evaluation tool in clinical cariology].
AB  - As a result of the caries prevalence of the Dutch population the character of the
      routine dental examination is changing. Caries screening remains relevant for
      high caries risk individuals but the interpretation of early caries lesions
      deserves more attention, especially the assessment of progression of caries
      lesions in time. Diagnosis of caries by dental practitioners in the Netherlands
      mainly consists of visual inspection in combination with bitewing radiography and
      both methods play an important role in the timing of bitewing radiographs and
      forthcoming recall visits for oral health examination. The content and frequency
      of the routine dental examination are discussed in relation to the individual
      risk prediction as relevant aspects of quality of dental care in the Netherlands.

PMID- 14710618
TI  - [Prevention on track? Reinforcement requested].
AB  - The improvement of the dentition of children starting in the seventies of last
      century has come to a halt. There are indications that the interest of children
      and young parents in dental health is declining. The government shows fewer
      activities to inform the public on dental health issue by mass communication. The
      future of dental health education by child care organisations or school medical
      services is uncertain. A great deal of dental health education has to be given in
      the dental office. In spite of all the preventive efforts in the past, there is a
      group of children still at high risk for dental caries. Older people may all
      become at risk when the interest in dental health or the ability for self care
      declines. New ways are to be sought to motivate these risk groups for adequate
      dental care. Parents, teachers, school medical services but also children of
      older people and volunteer and professional aid for the elderly should be
      involved.

PMID- 14710619
TI  - [Dental care for the handicapped patient].
AB  - In the last years the caries risk in the Netherlands has shifted to vulnerable
      groups consisting of people unable to commit themselves to independent preventive
      dental care. These groups, children with behaviour management problems, mentally
      disabled, and elderly people make a change in the perspective of preventive
      dental care necessary. A more individual approach is advised. The costs of the
      changes possibly have to be drawn from the regular dental budget.

PMID- 14710620
TI  - [Sealing of pits and fissures].
AB  - Sealing of pits and fissures depends on patient- and tooth factors. Prevention of
      occlusal carious is indicated for children with a high caries risk and especially
      when the morphology makes teeth more susceptible for developing caries (deep pits
      and fissures). Good occlusal caries diagnosis is difficult and a golden standard
      does not exist. When sealing of pits and fissures is indicated a preventive or a
      therapeutic approach can be chosen. A generally accepted guideline for sealing is
      still missing. Every approach has its advantages and disadvantages and depends on
      the individual operator.

PMID- 14710621
TI  - [Caries profunda: current views and treatment concepts].
AB  - Current insight of the caries process demands new, more selective and less
      invasive techniques and methods for excavation. Nowadays the biological aspects
      of teeth and pulp tissue in reaction to caries need to be respected and even
      used. The general practitioner is confronted with a wide range of new techniques
      and methods and needs to choose the best suitable. The purpose of this article is
      to inform the general practitioner about the current views concerning treatment
      of caries profunda and the different treatment concepts. Thereby the authors hope
      to assist the general practitioner in their choice for the proper treatment.

PMID- 14710622
TI  - [Dental caries in the Netherlands at the turn of the century].
AB  - In this paper an overview is given of recent studies concerning the prevalence of
      dental caries in children and adults in The Netherlands. Compared to the oral
      status in the past, the prevalence in children is still low. The decrease of
      caries is now also visible in adults up to the age of 45 years. The caries
      experience of people in older age categories is still high. A significant
      relationship was found between caries prevalence in children and level of school
      education of the mother and between caries experience of adults and their level
      of school education. A relatively high caries prevalence was found in children
      whose mothers were born in Turkey or Morocco. On the other hand, adults born in
      these countries had a lower caries experience than native Dutch adults.

PMID- 14710623
TI  - [Cariology, making the balance].

PMID- 14710624
TI  - Relating parasite communities to host environmental conditions using phylogenetic
      tools.
AB  - There are many tools available for analysing parasite communities, either based
      on the proportions or presence/absence of species. These analyses rely on
      phylogenetic distances, and analyses of actual characters (e.g. species). The
      phylogenetic analysis (Wanger parsimony) was compared to a cluster analysis
      (UPGMA) and correspondence analyses of two real helminth communities in sheep
      (one farm and with repeated sampling along time) or goats (several farms, each
      sampled once). The cladograms obtained using Wagner parsimony provided a clearer
      structuring of the helminth communities than classical analyses. The homogeneous
      groups of parasite communities on goat farms were significantly related (Fisher'
      exact test) to the environmental characteristics. The evolution along time
      pattern of change in the sheep infection of sheep was not the same for in all the
      animals, and two groups of communities could be distinguished in the last lamb
      cohorts. Phylogenetic analyses provide an effective performing tool to for
      interpreting the change in evolution of helminth communities with environmental
      conditions.

PMID- 14710625
TI  - Detection and counting of Cryptosporidium parvum in HCT-8 cells by flowcytometry.
AB  - The objective of the present study was to evaluate flowcytometry analysis (FCA)
      as a tool for rapidly and objectively estimating the percentage of cells infected
      with Cryptosporidium parvum in an in vitro model. We compared the results to
      those obtained with immunofluorescence assay (IFA) and evaluated the intra-assay
      variability of both assays and the inter-assay variability of IFA. Human
      ileocecal adenocarcinoma cells (HCT-8) were infected with different doses of
      excysted oocysts. After 24 hours, cells were analysed by FCA and by IFA using a
      monoclonal antibody that recognises a C. parvum antigenic protein and a lectin
      that binds with glycoproteins present in the parasitophorous vacuoles. The
      coefficient of variability in terms of the percentage of infected cells was lower
      for FCA (i.e., 13-14%) than for IFA (i.e., 27-38% when performed by a single
      operator and 19-22% when performed by three operators), suggesting that FCA is
      more accurate, in that it is not subject to operator expertise. FCA also has the
      advantage of allowing the entire culture to be examined, thus avoiding problems
      with heterogeneity among microscopic fields. In light of these results, this
      method could also be used to test new anti-Cryptosporidium drugs.

PMID- 14710627
TI  - Progamotaenia capricorniensis sp. nov. (Cestoda: Anoplocephalidae) from wallabies
      (Marsupialia: Macropodidae) from Queensland, Australia.
AB  - Progamotaenia capricorniensis sp. nov. (Cestoda: Anoplocephalidae) is described
      from the wallabies Macropus dorsalis (Gray, 1837) and Petrogale assimilis Ramsay,
      1877 from Queensland, Australia. The new species is characterised by a fimbriated
      velum composed of 26-32 digitiform to triangular projections on each side of the
      proglottis, paired uteri and 140-190 testes distributed in a single band across
      the medulla. Minor variation occurs in the distribution of the testes. The above
      characters distinguish the new species from its most closely related congeners P.
      lagorchestis (Lewis, 1914), P. proterogyna (Fuhrmann, 1932), P. spearei
      Beveridge, 1980 and P. villosa (Lewis, 1914). P. capricorniensis appears to
      exhibit a highly disjunct distribution within its usual host, M. dorsalis.

PMID- 14710626
TI  - Effect of Anapsos in a murine model of experimental trichomoniasis.
AB  - Immunomodulator effect of Anapsos (Polypodium leukotomas extract) in NMRI (US
      Naval Medical Research Institute) outbred mice infected by the intraperitoneal
      route with 10(7) Trichomonas vaginalis has been tested. Gross histopathologic
      changes in abdominal organs and mortality rate, as a consequence of the
      pathogenicity of the protozoa and the immune response of the host, were
      evaluated. Among the different treatment regimes assayed, Anapsos at doses of 20
      mg/Kg/day administered for 10 days before infection decreases the parasite
      pathogenicity index (PI) in the treated animals when compared to those of the
      untreated control group. The immunosuppressor treatments with azathioprine (100
      mg/Kg/day x 1), cyclophosphamide (100 mg/Kg/day x 1), and FK-506 (10 mg/Kg/day x
      10) significantly decreased the PI, while an immunostimulant treatment with
      glycophosphopeptical (13 mg/Kg/day x 10) increased it. These assays have shown
      the usefulness of the murine model of experimental trichomoniasis for the study
      of immunomodulator activity of natural or synthetic drugs.

PMID- 14710628
TI  - Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: V. Five new
      species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius Nasutus.
AB  - The examination of gill parasites from Pangasius nasutus (Bleeker, 1862)
      (Siluriformes, Pangasiidae) revealed the presence of five new species of
      Monogenea, all belonging to Thaparocleidus Jain, 1952 (Monogenea,
      Ancylodiscoididae) as defined by Lim (1996) and Lim et al. (2001): T. serpens n.
      sp. T. ocrea n. sp., T. megagripus n. sp., T. citreum n. sp. and T. alatus n. sp.

PMID- 14710629
TI  - Larval trypanorhynchs (Platyhelminthes: Eucestoda: Trypanorhyncha) from black
      scabbard fish, Aphanopus carbo and oceanic horse mackerel, Trachurus picturatus
      in Madeira (Portugal).
AB  - Four different types of trypanorhynch postlarvae were found attached to the
      stomach mucosa, external stomach wall or free in the body cavity of two marine
      fishes from Madeira, namely blackscabbard fish, Aphanopus carbo and oceanic horse
      mackerel, Trachurus picturatus. Morphological features shown by SEM indicated
      that the postlarvae belonged to the species Tentacularia coryphaenae,
      Sphyriocephalus tergestinus, Nybelinia lingualis and possibly N. yamaguitii.
      Prevalence [mean intensity (range)] of T. coryphaenae, S. tergestinus and
      Nybelinia spp. in A. carbo (n = 135) was 12.6% [1.65 +/- 1.27(1-6)], 5.9% [1.57
      +/- 0.79 (1-3)] and 2.2% [1.33 +/- 0.58 (1-2)] respectively. The prevalence of T.
      coryphaenae and S. tergestinus showed some seasonality, with a rise in prevalence
      of T. coryphaenae corresponding to a decrease in prevalence of S. tergestinus.
      However these differences were not significant. In T. picturatus (n = 304) only
      N. lingualis was found at a prevalence of 9.6%. Both S. tergestinus and N.
      lingualis were recovered only from the stomach mucosa or external stomach wall,
      while T. coryphaenae was observed either attached to the stomach mucosa or free
      in the visceral cavity of the fish. The paper presents the first scanning
      electron micrographs (SEM) of Sphyriocephalus tergestinus and a new geographical
      record of N. lingualis in T. picturatus.

PMID- 14710630
TI  - Redescription of four species of Mehdiella from Testudinidae, with a key to the
      species and discussion on the relationships among the species of this genus.
AB  - Four species of the genus Mehdiella Seurat, 1918 are redescribed: M. cristata
      Petter, 1966 and M. stylosa dollfusi Petter, 1966, parasite of Pyxix arachnoides
      Bell, 1827 from Madagascar, M. s. stylosa (Thapar, 1925) and M. uncinata
      (Drasche, 1884), parasite of Testudo graeca Linneaus, 1758, Testudo hermanni
      Gmelin, 1789 and Testudo horsfieldii (Gray, 1844) from Palaearctic region. Light
      microscopy and scanning electron microscopy (SEM) studies revealed new
      informations on the morphology of these species. On the basis of this
      morphological study, the sub-species Mehdiella stylosa dollfusi and M. s. stylosa
      are raised to level of species. The position of Mehdiella cristata among the
      species of the genus Mehdiella and the relationships among the species of the
      genus Mehdiella are discussed. A key to the eight valid species Mehdiella is
      given.

PMID- 14710631
TI  - Helminth parasites of cats from the Vientiane province, Laos, as indicators of
      the occurrence of causative agents of human parasitoses.
AB  - A total of 55 domestic cats (Felis catus f. domestica) and one wild (Bengal) cat
      (Prionaluirus bengalensis) from the Vientiane Province, central Laos, were
      examined for helminth parasites with emphasis given to potential human parasites.
      The following species were found (parasites infective to man marked with an
      asterisk): Opisthorchis viverrini, Haplorchis pumilio, H. taichui, H. yokogawai,
      Stellantchasmus falcatus (Digenea); Spirometra sp., Dipylidium caninum, Taenia
      taeniaeformis (Cestoda); Capillariidae gen. sp., Toxocara canis, T. cali,
      Ancylostoma ceylanicum, A. tubaeforme, Gnathostoma spinigerum, Physaloptera
      preputialis (Nematoda); and Oncicola sp. (Acanthocephala). This study
      demonstrated that examination of cats may provide useful data on the occurrence
      of helminths which are potential causative agents of human diseases.

PMID- 14710632
TI  - Two new fleas (Siphonaptera: Ceratophyllidae: Leptopsyllinae) of Madagascar:
      Tsaractenus rodhaini n. sp. and Paractenopsyllus (Consobrinopsyllus n. subgen.)
      goodmani n. sp.
AB  - Following considerable sampling in Malagasy forests, two new species of endemic
      fleas from Madagascar are described. These are T. rodhaini n. sp. and P. goodmani
      n. sp., collected on small mammals. The material of T. rodhaini allows us to
      describe the previously unknown female of the genus Tsaractenus. We also complete
      the initial description of the genus with new diagnostic characters. Although it
      belongs to Paractenopsyllus, P. goodmani shows many unique characteristics. To
      help resolve certain systematic issues involving Malagasy Leptopsyllinae we
      introduce the new subgenus Consobrinopsyllus of Paractenopsyllus for P. goodmani.
      Its particular condition makes us consider valuable characters of the genus
      Tsaractenus. Carrying several traits of this genus, P. goodmani could constitute
      an intermediate step between the two endemic Malagasy leptopsylline genera.
      Considering these new findings the actual taxonomic position of the Malagasy
      genera among the Leptopsyllinae is discussed.

PMID- 14710633
TI  - Efficacy of mosquito nets treated with a pyrethroid-organophosphorous mixture
      against Kdr- and Kdr+ malaria vectors (Anopheles gambiae).
AB  - In order to prevent the resistance of Anopheles gambiae s.l. to pyrethroids from
      spreading too quickly and to lengthen the effectiveness of insecticide
      impregnated mosquito nets, it has recently been suggested to use mixtures of
      insecticides that have different modes of action. This study presents the results
      obtained with tulle mosquito nets treated with bifenthrin (a pyrethroid) and
      chlorpyrifos-methyl (an organophosphorous) both separately and in mixture on two
      strains of An. gambiae, one sensitive to all insecticides, and the other
      resistant to pyrethroids. The values of KDt50 and KDt95 and the mortality induced
      with the mixture of bifenthrin (25 mg/m2) and chlorpyrifos-methyl (4.5 mg/m2)
      show a significant synergistic effect on the strain of An. gambiae susceptible to
      insecticides. However, the tested combination does not induce any synergistic
      effect on the VKPR strain selected with permethrin, but only enhances the
      effectiveness of the two insecticides taken separately.

PMID- 14710634
TI  - Changes in Plasmodium falciparum gametocytaemia in children with chloroquine
      sensitive asexual infections.
AB  - A non-compartmental pharmacokinetic model was used to describe the changes in
      gametocytaemia in nine children with chloroquine-sensitive Plasmodium falciparum
      malaria in whom asexual parasitaemia cleared within 72 h of chloroquine
      treatment. Peak gametocytaemia was 74 +/- 19.9 (se), range 24-198, geometric mean
      58 sf (sexual forms)/microliter. Time to peak gamelocytaemia was 43.2 +/- 14.4,
      range 0-120 h. Following peak gametocytaemia, gametocytes persisted in blood for
      a period of 168-504 h. The decline from peak gametocytaemia was exponential with
      a half-life of gametocytaemia of 43.2 +/- 20.4, range 13.1-206 h. The mean pre
      treatment sex ratio was male-biased and remained so till complete elimination of
      gametocytaemia. Peak microgametocytaemia, area under the curve of
      microgametocytaemia versus time, and the half-life of microgametocytaemia were
      significantly higher than those of macrogametocytaemia. The volume of blood
      completely cleared of macrogametocytaemia per unit time was significantly higher
      than that of microgametocytaemia. Macrogometocytes are cleared from the
      circulation faster than microgametocytes but chloroquine treatment of chloroquine
      sensitive infections has little or no significant effect on gametocyte sex ratios
      in this group of children.

PMID- 14710635
TI  - Effect of two formulations of benzimidazole carbamates on the viability of cysts
      of Echinococcus granulosus in vivo.
AB  - Two different preparations, solution and suspension, of three benzimidazole
      carbamate drugs, mebendazole, albendazole and ricobendazole, were compared by
      analyzing their in vivo activity against Echinococcus granulosus cysts in a mouse
      model. Polyvinylpyrrolidone was used for the elaboration of drug solutions and
      these formulations manifested better results in terms of reduction of number of
      viable hydatid cysts in mice than the reference drug suspensions. The effect was
      more prominent on mebendazole-treated mice, at doses of 25-50 mg/kg. There was a
      correlation between ED50 and pharmacokinetical parameters of AUC0-infinity and
      Cmax, showing that a significant improvement on solubility affects the in vivo
      activity of these drugs.

PMID- 14710636
TI  - First record of Mastophorus muris (Gmelin, 1790) (Nematoda: Spiruroidea) from a
      wild host in South America.
AB  - Mastophorus muris (Gmelin, 1790) (Nematoda: Spiruroidea) is reported parasitizing
      the grey leaf-eared mouse Graomys griseoflavus (Waterhouse, 1837) (Rodentia:
      Sigmodontinae) from the province of La Pampa, Argentina. The distinct position of
      Mastophorus (Spirocercidae: Mastophorinae) and Protospirura (Spiruridae),
      sometimes still confused, is again confirmed. The pattern of pseudolabial teeth
      (a large central tooth with smaller teeth on each side), which seems to be rather
      stable in all known descriptions, is here confirmed with the aid of scanning
      electron microscopy. The finding represents the first record of the species in
      Argentina, but also from a wild host in South America. This indicates an
      expansion of the distribution range of the species, which, in the subcontinent,
      was hitherto restricted to domestic rodents.

PMID- 14710638
TI  - First two cases of human dirofilariasis recorded in Croatia.

PMID- 14710637
TI  - Specific IgE induced by Kudoa sp. (Myxosporea: Multivalvulida) antigens in BALB/c
      mice.
AB  - The majority of Kudoa species infect the somatic muscle of fish establishing
      cysts. As there is no effective method to detect infected fish without destroying
      them, these parasited fish reach the consumer. We have developed this work to
      determine whether this parasite contains antigenic compounds capable of provoking
      an immune response in laboratory animals, in order to consider the possible
      immunopathological effects in man by the ingestion of Kudoa infected fish. BALB/c
      mice were injected by the subcutaneous route with the following extracts
      suspended in aluminium hydroxide: Group 1 (black Kudoa sp. pseudocyst extract),
      group 2 (white Kudoa sp. pseudocyst extract). Specific IgE levels were measured
      by ELISA. IgE detected in both groups 1 and 2 showed the possible allergenic
      nature of some of the components of the parasitic extracts.

PMID- 14710639
TI  - [Legal problems of physicians in hospitals].

PMID- 14710640
TI  - [Structure and limitations of past and future functions of hospitals in Germany
      from the physicians's point of view].
AB  - The present paper describes the emergence of hospitals from the xenodochia of the
      early Christian period up to the hospitals founded in the middle of the 19th
      century. Based on this tradition the development of German hospitals up to the
      present day has been influenced by the increase in scientific medical knowledge
      (anaesthesia, asepsis, antisepsis, roentgenology). Also, the differentiation of
      the traditional medical specialties into additional special fields and branches
      will be illustrated. Here, a special role may be attributed to both the laws and
      regulations releasing hospitals from the care for the invalid and elderly and a
      change in the prerequisites for hospital financing, which finally led to today's
      German hospitals being "acute care hospitals". Especially after World War II, the
      organisation and management structure of German hospitals were also affected by
      socio-political changes; it will be emphasised that the pyramidal structure
      (hierarchy) of quality, experience and competence is an indispensable
      requirement, which particularly applies to the structure of the medical staff.
      When a human being falls ill he does so as an entire psychophysical unit; the
      medical care for the diseased person must therefore not regard this unit that
      forms man as arbitrarily divided individual sections. The development of modern
      health technologies (such as--to mention just a few--dialysis, ultrasound,
      endoscopy, cardiac catheterisation, computed tomography, magnetic resonance
      imaging) should not lead to a complete autonomy of process engineers and thus to
      the splitting up of medicine into individual allotments because such an approach
      would be based on an utterly erroneous perception of man. In German hospitals,
      measures of internal quality assurance have been known for ages, long before
      politicians also discovered the necessity of so-called external quality assurance
      in medicine. Quality assurance has always been a matter-of-factness with
      hospitals. The presentation of the quality of hospital care to the outside world
      is a necessity. Scientifically founded clinical guidelines will be welcome in
      hospitals if they identify the necessary lower limit on medical practices by
      summarising the world-wide knowledge about diagnosis and treatment and if they
      are regularly checked and updated. But guidelines determining an upper limit on
      medical practices serve economical purposes only, fixing the manoeuvring space
      for practising the art of medicine to the disadvantage of the patients and
      transforming medicine from an attention-giving into an allocation-oriented
      profession. The future of German hospitals will only partially depend on the
      progress achieved in the medical sciences; to a greater extent it will be
      restricted by political decisions and general economic conditions.

PMID- 14710641
TI  - [Structure and limitations of German hospitals with regard to the future--the
      example of the Vivantes Group].
AB  - The German health care system is marked by increasing tension between rising
      needs, financiability and reformability. Structural deficits and a high
      performance potential are typical of the German hospital system. In these terms,
      Berlin occupies a leading position in the intra-national comparison. The
      introduction of a new payment system for hospitals that is based on case fees
      (DRGs) will lead to a radical reorganisation of hospitals in both quantity and
      structure. The health care provider Vivantes brings a clear answer to this
      challenge: even today this group offers a graduated and complex network
      integrating outpatient, inpatient, nursing and rehabilitative care units--whilst
      steadily reducing the capacities required. The integration of external
      enterprises is capable of improving the network both qualitatively and
      economically and offering a win-win situation. Integrative purchase-of-service
      contracts should be formulated to give a noticeable advantage to providers,
      sickness funds and insured persons.

PMID- 14710642
TI  - [Work-time regulations--organization--liability and financing. Why young
      physicians run away from hospitals].
AB  - Junior doctors refuse to work in German hospitals as working conditions are
      outrageous. The German Working Time Law has not correctly transposed the European
      Union's Working Time Directive (EU 93/104). The Marburger Bund is fighting for a
      reform of the working conditions and has developed a new model for organising
      working hours, which would not only lead to a correct transposition of the EU
      Directive, but would also bring better working conditions and better patient care
      to German hospitals.

PMID- 14710643
TI  - [Compensation for hospital-based physicians].
AB  - In German hospitals there are four groups of physicians associated with different
      compensation schemes: the senior consultants receiving both a salary from the
      hospital and fees earned from ambulatory and stationary private patients; house
      officers (residents) receiving a salary, overtime allowance and a share in the
      senior consultants' fees; external doctors with a hospital affiliation
      (Belegarzte) receiving only the fees paid by patients or their health insurers;
      medical consultants (Konsiliararzte) earning fees for optional services from
      private patients, for other services from the hospital.

PMID- 14710644
TI  - [Labor law issues in hospitals by structural changes and changes in hospital
      ownership].
AB  - The present article deals with the potential impact of structural changes and
      changes in hospital control or ownership on the employment contracts of the
      physicians concerned. While taking the applicable jurisdiction into
      consideration, the author examines the options of assigning new responsibilities
      or decreasing compensation opportunities, amending or even terminating employment
      contracts, outsourcing hospital-related services, or allowing physicians in the
      future to provide these services at their own risk. Furthermore, the article
      outlines the change in employer in various "change of control" scenarios such as
      in the case of hospital privatisation.

PMID- 14710645
TI  - [Conflict situations in a hospital in the case of a civil lawsuit].
AB  - In the case of possible malpractice the physician is threatened with various
      legal proceedings. These may range from civil lawsuits including out-of-court
      settlement, independent evidential procedures (sections 485 et seqq.), criminal
      litigation and proceedings at the labour court to the withdrawal of the
      registration as a panel doctor. The annual number of civil lawsuits for damages,
      pain and suffering is estimated as approximately 10,000. In 35% of all cases
      expert commissions decide on malpractice; 85% are settled out of court so that
      15% of cases proceed with litigation in a civil court. Of special importance to
      the physician sued in malpractice litigation is his pre-trial strategy. The
      present paper names the most important basic rules. The physician's failure to
      comply with these rules may result in severe penalties including the loss of
      malpractice insurance.

PMID- 14710646
TI  - [Situation of legal conflicts in criminal proceedings].
AB  - Criminal proceedings against physicians involving an alleged professional
      malpractice usually represent a complex problem raising issues in various
      (potential) areas of conflict. In many cases such proceedings are accompanied by
      liability actions in civil courts, occasionally proceedings have been initiated
      by the Medical Board in order to clarify a case of professional misconduct.
      Often, a medical malpractice insurance is involved. In order to protect the
      physician's interests in the best possible way, any action in the various matters
      needs concerted efforts. No statement or comment regarding the allegations should
      be rendered to the prosecution before access to the investigation file has been
      granted. No negative conclusions may be drawn from the use of the right to refuse
      testimony. The preparation of a written statement requires a thorough legal and
      factual analysis of the allegations as well as the evidence they are based on. In
      this respect professional legal assistance is essential. It does not constitute a
      breach of the doctor-patient confidentiality if the physician discloses
      information in order to defend himself against criminal allegations. If several
      physicians are charged with an offense it is recommendable in most cases to
      coordinate defense activities.

PMID- 14710647
TI  - [Legal conflict situations with the Code of Professional Medical Conduct].
AB  - The health care marketplace is undergoing a major transformation that is
      characterised by the increasing competition between hospitals and physicians.
      Heads of medical departments are nowadays requested to undertake not only medical
      and management but also marketing functions. Hospital brochures, internet
      presentations, press conferences, polls and other tools are used for marketing
      purposes. The present article describes the legal possibilities and limitations
      of hospital marketing in Germany.

PMID- 14710648
TI  - [Legal aspects of conflict situations from the hospital physician's perspective].
AB  - The majority of hospital physicians have already adapted to "normal conflict
      situations". Standards in patient information, diagnosis, treatment and follow-up
      have become established practice as have the resultant consequences of the
      failure to observe these standards, possibly on the basis of guidelines and
      directives. The legal developments in recent years make organisational
      shortcomings and mistakes in taking on patients without any requisite
      specialisation a liable offense. Similarly, faulty documentation is a much
      discussed medical and legal issue. New fields of legal dispute arise from the
      growing financial pressure and the increasing managerial responsibilities placed
      on senior physicians. Likewise, budgeting requirements and legal claims of
      employees based on working time legislation may also bear legal consequences.
      With the introduction of a flat-rate remuneration system for hospital services
      (DRGs: diagnosis related groups), liability claims against senior physicians due
      to coding errors have been included in the contractual agreements. Serious new
      conflicts essentially arising from time pressure and the overloading of
      physicians with bureaucratic, financial and administrative tasks can only be
      satisfactorily resolved if doctors are allowed to do what they are intended to do
      and if they are provided with the time and financial resources their every day
      work and continuing medical education require.

PMID- 14710649
TI  - [Authorization, institutional services, hospital-based practices and cooperation
      in the hospital--from the perspective of the hospital-based physician].
AB  - The partitioning of patient care into an ambulatory and stationary sector, which
      has been in existence for decades, was wanted from a general political and
      economic point of view and has since been a guarantee for high-quality care in
      both sectors. The demographic development and scientific medical advances leading
      to higher life expectancy in the face of increasingly sparse resources have made
      us recognise that there might be a considerable cost-saving potential in
      promoting stronger integration of stationary and ambulatory care. The trend
      towards increased specialisation of the medical profession, but also the
      emergence of new professions within the health care sector require increasing
      efforts to ensure consistent courses of treatment and the necessary
      interdisciplinary and interprofessional continuity. But given insufficient
      budgets and the resultant distribution conflicts within this system the situation
      will become more critical. Integration does not simply happen, it must be wanted,
      designed and organised. It is dependent on crossborder co-operation and interface
      competence, especially general conditions promoting instead of inhibiting co
      operation and integration. This requires an integrative system of patient care
      opening its borders on both sides. If this system which is intended to ensure an
      open and holistic concept of care is to be directed towards the individual
      patient, the transfer of care between the ambulatory and stationary sectors must
      not be system-related and thus imply that the patient will have to change his
      doctor(s) without being asked. Integrative care can and will be successful if
      general conditions are established that allow the medical profession to meet the
      challenges of integration and interface organisation, the lack of which is the
      result of misguided health care policy and not a failure that can be blamed on
      health care providers.

PMID- 14710650
TI  - [Authorization, institutional services, hospital-based practices and cooperation
      in the hospital--from the point of view of the hospital owners].
AB  - Structural changes in the financing of hospital-based health care in Germany make
      a revision of the currently existing strict separation between ambulatory and
      stationary patient care inevitable. The present monopolist situation of office
      based physicians (organised in private practices without any legal or financial
      relation to a hospital) will be amended by the participation of hospitals and
      hospital-employed doctors in ambulatory services of a different kind. These may
      include the institutional authorization of hospitals to participate in ambulatory
      services, especially in the case of emergencies and first aid, and co-operations
      between doctors in private practices and hospitals. Such co-operations are now
      legally enabled to provide "integrated services", but still lacking acceptance by
      the parties involved in the health care services. Ambulatory medical care is an
      already huge and now rapidly growing market, whereas the classical hospital
      services represent a declining product. Therefore hospitals will have to act
      accordingly or they will even forfeit the opportunity to use the ambulatory care
      sector to improve the intensity of utilisation of their hospital beds. In
      addition, hospitals will have to accept that office-based doctors are their
      customers and have to be treated as such. The establishment of regional networks
      may be a solution to this problem. Integrated services can only be established if
      new ways of co-operation and knowledge transfer are introduced into this area
      step by step. The present article provides practical examples of co-operation
      models.

PMID- 14710651
TI  - [Networking: ambulatory and stationary mesdical care].
AB  - A better co-operation between health care sectors and primary and specialised
      treatment levels is inevitable for ensuring good patient care. Many informal co
      operations already exist, and their experience may be used for developing new
      forms of co-operation. Therefore, the existing legal basis has to be changed,
      barriers must be abolished and new incentives established. Quality management
      that is both practicable and adapted to the needs of these new forms of patient
      care must be an integral part of this development.

PMID- 14710652
TI  - [Legal implications of the interlocking of ambulatory and stationary care].
AB  - In Germany, ambulatory and stationary care are separated at both a legal and an
      organisational level. For some time though there have been efforts to make the
      border between these two sectors of care more permeable. However, the measures
      that have been implemented in order to achieve this goal such as the forms of
      integrated care in accordance with sections 140 a et seqq. of the Fifth Book of
      Social Code (SGB V) have yet failed to meet with the intended success, which is
      due to a lack of co-operation between the two sectors. One of the reasons is
      economic: on the one hand, the interlocking of the two sectors of care is
      supposed to bring about increased and more efficient co-operation between
      providers of care, on the other hand, though, these terms may easily be reduced
      to a single outcome, that is being "cheaper". The other is that medical
      professionals suffer from a legally founded fear of contact resulting from the
      difficult legal separation of areas of responsibility and liability between
      ambulatory and stationary care. There are considerable differences between the
      two sectors in respect of both organisational and clinical issues so that the
      respective liability parameters are of a different nature and different legal
      relevance.

PMID- 14710653
TI  - [The hospital physician in the conflict between ambulatory and inpatient care].
AB  - The case presented demonstrates the typical risk a physician with a hospital
      affiliation--here: an otorhinolaryngologist--faces in performing ambulatory
      surgery procedures. After tonsillectomy recurrent haemorrhage was seen in a 5
      year old patient during the first two postoperative weeks. Though the patient is
      finally admitted to a hospital, a further night-time bleeding episode fails to
      get duly recognised and appropriately controlled. This failure results in a
      central nervous system damage leaving the child severely and multiply disabled.
      Five medical experts differ in their judgement of the question whether the
      attending physician failed to observe medical standards and whether the CNS
      damage was caused by this failure. The court judged the physician's negligence to
      be a crude medical error thus leading to a shift in the burden of proof. A legal
      action for damage against the physician could be successfully filed.

PMID- 14710654
TI  - [Conflict between inpatient and outpatient care. Summary of the discussion].

PMID- 14710655
TI  - [Risk management from the physician's perspective].
AB  - Risk Management in a hospital is intended to recognise, manage and potentially
      eliminate existing risks by implementing suitable preventive measures as early as
      possible. Physicians in all areas of responsibility in a hospital are called upon
      to support such efforts by active co-operation. Co-operation and communication, a
      clear distribution of responsibilities, obligatory instructions, elimination of
      organisational deficiencies, regular information to staff and circulation of
      written agreements are both useful and necessary.

PMID- 14710656
TI  - [Risk management from the hygienist's perspective].
AB  - Each year numerous patients acquire nosocomial infections in our hospitals, but
      the proportion of nosocomial infections that could potentially be prevented by
      infection control measures applied under routine working conditions remains
      unclear. Experts estimate that at least 20% of all nosocomial infections are
      likely to be avoidable. Various studies demonstrated that nosocomial infections
      can be significantly reduced by appropriate intervention methods in hospitals
      that are interested in quality management activities. However, continuous efforts
      are necessary to maintain these improvements. Also, hospitals must implement a
      wide range of policies designed to limit liability, some of which may only be
      marginally relevant to medical necessity. Persons working in the field of
      infection control therefore must have an understanding of both the medical and
      legal implications of their work, and those trained in the field of hospital
      epidemiology and infection control represent valuable support resources of
      today's hospitals.

PMID- 14710657
TI  - [Risk management from the perspective of the hematologist].
AB  - The present paper deals with the physician's accountability during the
      implementation of hemotherapeutic measures. Since July 1, 1998 a Transfusion Law
      ('Transfusionsgesetz') regulates the clinical use of blood products in Germany in
      accordance with the guidelines established by the German Medical Association and
      the Paul Ehrlich Institute, which are regularly revised and adapted on the basis
      of current professional knowledge and technology. The therapeutic freedom allowed
      under the Code of Professional Medical Conduct is taken into account by the fact
      that the responsibility for hemotherapy in each individual case lies with the
      attending physician, no matter whether this applies to the diagnosis, the patient
      counselling or the administration of the transfusion itself. The administration
      of blood products, whether in hospital or a doctor's office, must follow certain
      quality-assumed rules governing transfusions as stipulated by the Transfusion
      Law. The responsibility for establishing regulations for hemotherapy and the
      introduction of a quality assurance system lies with the management of the
      treatment centre who appoint a specific physician as the hemovigilant
      ('Transfusionsverantwortlichen') who is responsible for meeting both these
      duties. The hemovigilant must be assisted by physicians specially appointed for
      transfusion measures (Transfusionsbeauftragte) who are responsible for the
      implementation of the hemotherapy regulations and quality assurance measures in
      the individual medical departments. As it is the hospital management's
      responsibility to ensure quality assurance, its duty also extends to monitoring
      the quality assurance system. Therefore a quality manager
      ('Qualitatsbeauftragter') will have to be appointed who must not be subject to
      directives. In case the management of the patient care centre does not fulfill
      the legal requirements or, for example, does not take action when shortcomings
      are discovered by the hemovigilant or quality manager that can only be dealt with
      by the management, then the organisational responsibility lies with the hospital
      management. Experience to date has demonstrated the success of the Transfusion
      Law. Whereas previously hospital managements have often failed to respond to
      suggestions for change or improvement, their attention may now be drawn to this
      law. This has led to blood products being increasingly used according to the same
      standards and keeping transfusing physicians on safe legal ground.

PMID- 14710658
TI  - [Risk management from the perspective of the radiation protection officer.
      Consequences of new radiation protection laws in hospitals].
AB  - The implications of the new radiation protection law for hospitals. The novel
      German radiation control regulation ("Roentgenverordnung") came into effect on
      July 1, 2002. It contains a number of new rules the majority of which clearly
      take a more restrictive approach towards the application of ionising radiation.
      New dose thresholds have been set for control and monitoring areas and written
      working instructions are now required for all areas of radiology departments. The
      new regulations also require the indication for a radiological examination to be
      checked by a radiologist who has completed a formalised training in radiation
      protection. This particular aspect will have serious implications for every day
      practice. The necessity of having a trained radiologist on site for 24 hours a
      day will cause problems in many hospitals. The power of the responsible external
      independent control body ("arztliche Stelle") has been increased as have the
      duties of medical physicists. The performance of x-ray examinations that are not
      medically indicated is punishable by law as bodily harm. This as well as many
      other regulations are currently being checked for applicability in terms of
      guidelines, the majority of which are not yet available.

PMID- 14710660
TI  - [Organizational malpractice. Summary of discussion].

PMID- 14710659
TI  - [Risk management from the judicial perspective].
AB  - The jurisdification of medicine is an unstoppable force that finds its visible
      expression in a medical liability boom which--apart from the negative impact of
      legal and out-of-court proceedings on the bond of the doctor-patient relationship
      -bears considerable economic disadvantages for the providers of care. It is
      therefore necessary to fight in particular the legally influenced causes of
      medical liability for which risk management seems to be a suitable, effective
      tool. As the examples taken from the jurisdiction in the organisational sector
      will demonstrate, risk management pinpoints the sources of trouble so that we are
      able to learn from current errors and provide appropriate remedies for the
      future. Risk management, though, is not a "unique event", but a dynamic,
      repetitive process that has to be institutionally secured by appointing a risk
      manager so that the proposals discussed, recommendations and essential measures
      can actually be implemented.

PMID- 14710661
TI  - [Quality assurance, quality management or quality control?].
AB  - The current concept of quality in the German health care system dates back to the
      period of the 1950s and 1960s, also including current legislation. Nevertheless,
      quality initiatives are in full progress. The German health care system is
      supposed to learn from experiences described in the fields of industry,
      technology and commerce. The philosophy and technology of quality management can
      provide an ideal solution to the common problems of the health care system.

PMID- 14710662
TI  - [Quality assurance versus regulations--the perspective of the medical director].
AB  - Quality assessment measures and measures leading to more quality improvement
      would be more than welcome to the medical profession. The mesh of institutions
      and methods needs to be simplified and should then be presented in a clear and
      understandable way to the physician who delivers curative care. Participation in
      quality assuring measures must be recognised as a matter of fact by the medical
      profession and be desired; regulating factors or even constraints, though, will
      lead to counter-productive effects and thus remain unsatisfactory.

PMID- 14710663
TI  - [Quality assurance versus regulation--the perspective of a lawyer].
AB  - In February 2003, the German Federal Ministry of Health presented a concept for
      establishing a German National Institute for Clinical Excellence. In sharp
      contrast to this concept, a closer look at other medical quality assurance
      activities in Germany shows that there is no area of responsibility in the German
      health care system where such an institution might prove useful. In Germany, the
      institutions of self-administration were the first to organise and promote
      medical quality assurance activities. The German Hospital Federation, the
      Association of Sickness Funds for salaried employees, the Association of Private
      Health Insurers, the professional organisations of German physicians and other
      organisations of self-administration entered into contracts pertaining to a
      medical quality partnership in order to create maximal benefit for all patients,
      i.e. to exactly address the patients' needs and treat their diseases with the
      best possible outcome. Such a framework of self-administration renders redundant
      the requirement for a German National Institute for Clinical Excellence.

PMID- 14710664
TI  - [Comprehensive ambulatory care quality management for patients with depressive
      disorders].
AB  - Depressive disorders are of great medical and political significance. Despite
      improvements in the treatment of depressive patients, the potential for guideline
      oriented diagnosis and therapy as well as better co-operation between different
      levels of care is evident. This study is part of the German Research Network on
      Depression and Suicidality. The study is conducted in Southern Baden, North Rhine
      and Munich. The objective is to develop a quality management program for primary
      care physicians and psychiatrists. A comprehensive continuous medical education
      concept as well as quality management measures were developed, implemented and
      evaluated. A total of 66 physicians (43 primary care physicians and 23
      psychiatrists) participated. They documented the diagnostic and treatment
      measures provided to depressive patients before and after the intervention that
      had been implemented in the intervention regions of Southern Baden and North
      Rhine. Effects regarding guideline orientation and implementation of stepped-care
      treatment are analysed with an intervention/control group design and prepost data
      measurement.

PMID- 14710665
TI  - [Clinical practice guidelines for the diagnosis and therapy of depressive
      disorders in primary care].
AB  - The guidelines for diagnosis and treatment of depressive disorders are practice
      oriented and evidence-based recommendations for primary care of depressive
      patients. They were developed in the context of subproject 3.1 "Comprehensive
      Quality Management in Outpatient Care" within the German Research Network on
      Depression and Suicidality. The guidelines were developed by research groups from
      study centres in Freiburg, Duesseldorf and Munich and an external expert group.
      In addition, a close co-operation was established with the Guideline Clearing
      Commission of the Agency for Quality in Medicine (AQuMed) and the Drug Commission
      of the German Medical Profession (AkdA) and are intended as an orientational aid
      in terms of a "pathway of care". The guidelines particularly address physicians
      in primary care. The development process followed the methodological
      recommendations of the Association of the Scientific Medical Societies in Germany
      (AWMF) and the requirements of evidence-based medicine. National and
      international guidelines for depressive disorders as well as Cochrane reviews
      (CR) and quality-assessed reviews (CRD) were taken into account. The present
      formulation of the treatment guidelines and the evidence was agreed upon in a
      consensus process that included all participants.

PMID- 14710666
TI  - [Development and evaluation of a basic documentation tool for guideline-oriented
      ambulatory care of depressive patients].
AB  - Quality assurance in the treatment of mental disorders is becoming increasingly
      significant. In this context, documentation systems are important in order to
      control the implementation of guidelines, to analyse shortcomings and to reveal
      improvement possibilities. Up till now there is no specific documentation tool
      for the outpatient care of depressive disorders. Within the project
      "Comprehensive Quality Management in Out-patient Care" a documentation tool for
      primary care as well as for psychiatric care of depressive patients has been
      developed, which embraces the principal diagnostic and therapeutic measures. This
      documentation tool consisting of an instrument for the physician to record the
      first consultation, a second instrument to record the following consultations as
      well as a patient questionnaire has been implemented and evaluated in primary
      care and psychiatric practices. The evaluation results demonstrate that the
      documentation tool is able to assess guideline-oriented treatment measures.
      Physicians evaluated the usefulness and practicability of the documentation tool
      positively. And although the documentation efforts required are quite extensive,
      this documentation tool provides a suitable basis for external or internal
      quality assurance as well as patient-oriented case-monitoring.

PMID- 14710667
TI  - [Agreement in physicians' and patients' assessment of depressive disorders].
AB  - Depression is one of the most frequently encountered mental health disorders in
      primary care. The health and financial burden caused by this disorder emphasise
      the clinical importance of depressive disorders. Research shows that these
      conditions often remain unrecognised and untreated. The aim of this study is to
      analyse if and how primary care physicians identify this condition in comparison
      to the patients' self-evaluation. A total of 1,233 cases in 32 primary care
      physicians' offices were examined to see if symptoms of depression were
      recognised. The assessment procedures were evaluated, too. In this study, the
      prevalence of depressive disorders was 10%, and the recognition rate of primary
      care physicians 45%. These results underscore the importance of improving
      physicians' recognition of depression and use of ICD-10 criteria for differential
      diagnosis. Conclusions must be drawn for a specific training of primary care
      physicians that focuses on the improvement of diagnosis and treatment of
      depressed patients.

PMID- 14710668
TI  - [Reason for encounter and diagnosis of depression in patients in general
      practice].
AB  - The present study investigates the extent to which the physicians' diagnosis of
      depression was influenced by the reason that patients gave for seeking help, i.e.
      the reason for encounter. The level of correspondence between the somatic
      diagnoses of 20 GPs and the self-ratings of 862 patients from the regions of
      North Rhine and Southern Baden in regard to the presence of a depressive syndrome
      was recorded. In addition to the somatic diagnosis of depression (yes/no), the
      reason for encounter as well as primary and secondary diagnoses of the
      participating GPs were also documented. The results show that approximately 10%
      of the GPs' patients judged themselves to be depressed and that in these
      patients, the GPs diagnosed depression in only 39% of cases. This low level of
      correspondence between physician and patient in regard to depression can be
      accounted for by the finding that first, there is little difference between
      depressed and non-depressed patients in the manner in which they distinguish
      themselves in regard to their reason for encounter and that second, depressed
      patients expressed more somatic (57%) than mental symptoms (20%). A depressive
      disorder was only reported for 5% of the patients who had judged themselves to be
      depressed. On the whole, the results have shown that the reasons for seeking
      treatment expressed by patients had a significant influence on correspondence
      between the physician and patient: for patients who had been judged by a
      physician and themselves to be depressed, mental complaints (34%) were more
      likely to be reported than for patients who had not been diagnosed with
      depression by their GPs (10%). Additional questions addressed to the physicians
      revealed that they were more likely to diagnose depression on the basis of the
      patients' self-ratings and behaviour than to routinely question the patients for
      symptoms of depression. Hence, the study underlines the need for training in
      criteria-orientated diagnosis and the application of suitable screening
      instruments for depressive disorders in general practice.

PMID- 14710669
TI  - [Subjectively-perceived inappropriate treatment of depressed patients in general
      and psychiatric practice].
AB  - In the present study, process quality in outpatient depression care was
      documented by general practitioners and specialists in psychiatry. Opportunities
      to improve inpatient treatment were identified by comparing current physicians'
      treatment procedures with guideline recommendations and, furthermore, by
      evaluating treatment outcomes from the patients' perspective. Data of 350
      depressed outpatients were collected by 43 GPs and 23 specialists in psychiatry
      in three study regions (Rhineland, South Baden and Munich). Data reflected
      psychopathology, diagnostic assessment, investigation of suicidal intentions as
      well as somatic and psychotherapeutic measures at the first visit. Additionally,
      change in depression symptoms after six to eight weeks by means of self-rating (n
      = 165) and expert rating (n = 70) was measured. The study shows that the GPs and,
      to a lesser extent, the specialists, still fail to orient themselves towards
      guideline recommendations regarding assessment, therapy and referral in
      depression care. These findings seem to be reflected in insufficient self rated
      treatment outcome: one half of the patients reported a reduction in depression
      symptoms, the other half of patients reported stagnation or even progression.
      Expert ratings of treatment courses were more positive. The results indicate a
      considerable need for guideline training and improvement of networking and co
      operation between GPs and specialists as well as between inpatient and outpatient
      settings.

PMID- 14710670
TI  - [Continuing education and quality management measures for the implementation of
      clinical practice guidelines].
AB  - In the past years it could be shown that evidence-based guideline-oriented
      treatment of depressive patients leads to better diagnosis, to more adequate
      therapy and to better networking of the different levels of care. And yet,
      guidelines have been rarely used. On the other hand, better short-dated support
      of depressive patients is achievable by medical education. But to ensure the
      application of guidelines in the long term, it is necessary to consider
      individual practice and local/regional conditions. There is a need for
      interactive and experience-oriented educational concepts. The present educational
      concept of "Out-patient Depression Management" has been developed as part of the
      "Comprehensive Quality Management in Out-patient Care" project and implemented in
      two study regions of Southern Baden and North Rhine. The depression management
      concept was designed as a combination of interactive, guideline-oriented
      continuous medical education with interdisciplinary quality circles. The
      evaluation of the depression management concept shows very positive ratings from
      both primary care physicians and psychiatrists: 70% of the primary care
      physicians and 83% of the psychiatrists were satisfied or much satisfied with the
      program. 70% of the primary care physicians and 50% of the psychiatrists
      evaluated the usefulness for practice as good or very good.

PMID- 14710671
TI  - [Cost optimization of the outpatient management of depression].
AB  - Against the background of the important role of depressive disorders in health
      policy, outpatient management still seems to have some optimisation potential. In
      particular, improvement can be expected from a stricter adherence to diagnostic
      and therapeutic guidelines. The article discusses potential elements of a quality
      orientated, guideline-based reimbursement system as a component of a
      comprehensive strategy for implementing available guidelines. This includes
      focussing on target areas typical of depression as well as improving outcome by
      controlling process elements during treatment.

PMID- 14710672
TI  - [Guideline-oriented patient information on depression--an example contributing to
      the provision of sound professional health information for patients and
      relatives].
AB  - It is a prerequisite of sound professional information on the various courses of
      the disease and available treatment options in order to guarantee that persons
      affected are actively involved in their individual treatment course or preventive
      measures. In the following article, guideline-oriented patient information on
      depression will be presented, which--as a result of a co-operation between AQuMed
      and the Department of Quality Assurance of the DGPPN--emerged from a series of
      lay information on psychiatric diseases.

PMID- 14710673
TI  - Getting ahead. Diversity becoming part of hospitals' business practice.

PMID- 14710674
TI  - 4-minute heroes.

PMID- 14710675
TI  - Back to basics.

PMID- 14710676
TI  - [Various mechanisms of mRNA degradation].

PMID- 14710677
TI  - [Adaptive mutations].

PMID- 14710678
TI  - [Protein S-thiolation as an antioxidative and regulatory mechanism].

PMID- 14710679
TI  - [The significance of polymorphisms in the human glutathione transferase genes].

PMID- 14710680
TI  - [The characteristics of ILT receptors].

PMID- 14710681
TI  - [Dolichols--long-chain isoprenoid lipids required for protein modification].

PMID- 14710683
TI  - Facility profile. Surgery center streamlines outpatient care.

PMID- 14710682
TI  - [The characteristic of ribulose-1,5-biphosphate carboxylase/oxygenase(rubisco).
      Directions of studies].

PMID- 14710684
TI  - Safe keeping.

PMID- 14710685
TI  - Taking charge. Developing a health care incident command system.

PMID- 14710686
TI  - Meshing missions. Integrating utility infrastructure master plans with ongoing
      facility renovations.

PMID- 14710687
TI  - Room with a view. Looking at the future of patient room design.

PMID- 14710688
TI  - Waste away. Composting programs take hold at pioneering health care facilities.

PMID- 14710689
TI  - New approaches to the treatment of sepsis.
AB  - The clinical spectrum of sepsis, severe sepsis, and septic shock is responsible
      for a growing number of deaths and excessive health care expenditures. Until
      recently, despite multiple clinical trials, no intervention provided a beneficial
      outcome in septic patients. Within the last 2 years, studies that involved
      drotrecogin alfa (activated), corticosteroid therapy, and early goal-directed
      therapy showed efficacy in those with severe sepsis and septic shock. These
      results have provided optimism for reducing sepsis-related mortality.

PMID- 14710690
TI  - Hemodynamic monitoring in the intensive care unit.
AB  - Hemodynamic monitoring is a diagnostic tool. Because hemodynamic monitoring often
      requires invasive procedures, it can be associated with an increased incidence of
      untoward events. Like any diagnostic tool, its ability to improve outcome will be
      primarily related to the survival benefit enjoyed by specific therapies that can
      only be given without complications based on their use. Presently, few specific
      treatment plans fit into this category. The diagnostic accuracy of preload
      responsiveness is markedly improved by the use of arterial pulse pressure or
      stroke volume variation, neither of which require pulmonary arterial
      catheterization. The field of hemodynamic monitoring is rapidly evolving and will
      probably continue to evolve at this rapid pace over the next 5 to 10 years as new
      technologies, information management systems, and our understanding of the
      pathophysiology of critical illness progresses.

PMID- 14710691
TI  - Critical issues in nephrology.
AB  - Renal and electrolyte problems are common in patients in the ICU. Several
      advances that occurred in the recent past have been incorporated in the diagnosis
      and management of these disorders and were reviewed in this article.
      Unfortunately, many important questions remain unanswered, especially in the area
      of ARF, where new therapies are anxiously awaited to make the transition from
      bench to bedside. Better studies are sorely needed to define the best approach to
      dialysis in patients who have ARF.

PMID- 14710692
TI  - Critical issues in endocrinology.
AB  - Endocrine emergencies are commonly encountered in the ICU. This article focuses
      on several important endocrine emergencies, including diabetic hyperglycemic
      states, adrenal insufficiency, myxedema coma, thyroid storm, and pituitary
      apoplexy. Other endocrine issues that are related to intensive care, such as
      intensive insulin therapy, relative adrenal insufficiency, and thyroid function
      test abnormalities are also covered in detail.

PMID- 14710693
TI  - Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood
      product transfusions in critically ill patients.
AB  - Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are
      essential to identifying and managing their causes successfully. In all cases,
      clinicians should evaluate RBC measurements alongside WBC and platelet counts and
      WBC differentials. Multiple competing factors may coexist; certain factors affect
      RBCs independent of those that affect WBCs or platelets. Ideally, clinicians
      should examine the peripheral blood smear for morphologic features of RBCs, WBCs,
      and platelets that provide important clues to the cause of the patient's
      hematologic disorder. Thrombocytopenia arises from decreased platelet production,
      increased platelet destruction, or dilutional or distributional causes. Drug
      induced thrombocytopenias present diagnostic challenges, because many medicines
      can cause thrombocytopenia and critically ill patients often receive multiple
      medications. If they suspect type II HIT, clinicians must promptly discontinue
      all heparin sources, including LMWHs, without awaiting laboratory confirmation,
      to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired
      protein C deficiency, thereby exacerbating the prothrombotic state of type II
      HIT, warfarin should be withheld until platelet counts increase to more than
      100,000/microL and type II HIT is clearly resolving. The presence of a
      consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis
      of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels,
      and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D
      dimer, levels are the most specific DIC parameter and reflect fibrinolysis of
      cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of
      factors or the presence of inhibitors. Clinicians should suspect factor
      inhibitors when the prolonged PT or aPTT does not correct or only partially
      corrects following an immediate assay of a 1:1 mix of patient and normal plasma.
      In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus
      anticoagulant) can produce a prolonged aPTT that does not correct with normal
      plasma but is overcome by adding excess phospholipid or platelets. Paradoxically,
      a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the
      antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or
      plasma products is sometimes warranted, but clinicians must carefully weigh
      potential benefits against known risks. In critically ill patients, administering
      RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not
      have ischemic heart disease, guidelines recommend a transfusion threshold of HGB
      levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least
      10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to
      increase erythropoiesis offers an alternative to RBC transfusion, assuming
      normal, responsive progenitor cells and adequate iron, folate, and cobalamin
      stores. Future research should examine whether clinical outcomes from rHuEPO use
      in critically ill patients are important and cost-effective. Because platelets
      play an instrumental role in primary hemostasis, platelet transfusions are often
      important in managing patients who are bleeding or at risk of bleeding with
      thrombocytopenia or impaired platelet function. Platelet transfusions carry
      risks, and decisions to transfuse platelets must consider clinical circumstances.
      Most important, platelet transfusions are generally contraindicated if the
      underlying disorder is TTP or type II HIT, because platelet transfusion in these
      settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma
      products can correct hemostasis when bleeding arises from malfunction,
      consumption, or underproduction of plasma coagulation proteins. Choice of plasma
      product for transfusion depends on clinical circumstances. FFP is the most
      commonly used plasma product to correct clotting factor deficiencies,
      particularly coagulopathies that are attributable to multiple clotting factor
      deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or
      rFVIIa that is administered in small volumes may provide advantages over FFP when
      coagulopathies require quick reversal without risk of volume overload. Factor
      concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses
      inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic
      abnormalities from severe liver dysfunction; extensive surgery, trauma, or
      bleeding; excessive warfarin anticoagulation; and certain platelet disorders
      requires further study to determine optimal and cost-effective dosing regimens.
      Recombinant activated protein C reduces mortality from severe sepsis that is
      associated with organ dysfunction in adults who are at high risk for death
      (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease,
      as do fibrinogen and platelet levels. Because of its anticoagulant effect,
      however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa
      use must take into account bleeding risks.

PMID- 14710694
TI  - Critical issues in digestive diseases.
AB  - This article discussed the diagnosis and management of acute GI bleeding,
      prophylaxis against GI bleeding, acute pancreatitis, and acalculous
      cholecystitis. These diseases are commonly encountered in the ICU setting. Acute
      GI bleeding is usually obvious and with GI and with available interventional
      radiologic techniques, patients rarely need surgery. Conversely, acalculous
      cholecystitis is difficult to diagnosis; therefore, a high degree of suspicion
      needs to be exercised with all critically ill patients.

PMID- 14710695
TI  - Nutritional support in critical care.
AB  - Despite the key role of nutrition in health and the almost universal use of
      supplemental feeding in the ICU, there is a lack of high-quality evidence to
      guide clinical practice. Enteral nutrition is superior to TPN in almost all
      circumstances and most patients in the ICU can be fed successfully by this route.
      There is little evidence to support the use of special feeds and the role of
      immunonutrients remains unproven. Nutritional support cannot completely prevent
      the adverse effects of catabolic illness and overfeeding should be avoided.

PMID- 14710696
TI  - A rational approach to the evaluation and treatment of the infected patient in
      the intensive care unit.
AB  - Critically ill patients are at increased risk of acquiring nosocomial infections.
      A thorough clinical evaluation and the selection of appropriate diagnostic
      techniques are important elements in the evaluation of these patients.
      Nonetheless, this selection process can be difficult because of the wide spectrum
      of disease that is seen in the ICU and the lack of standardized studies that have
      evaluated the different diagnostic methods that are available. Many different
      antimicrobials are available for the treatment of ICU-acquired infections. Most
      antimicrobial regimens have not been evaluated in large-scale, prospective,
      randomized trials. Until this information is available, the clinician must make
      an effort to be familiar with the different clinical and epidemiologic variables
      that can be used to stratify patients at the moment of selecting antimicrobial
      therapy. The information provided in this article, used in association with good
      clinical judgment, will help the critical care physician provide optimal initial
      management of the infected patient in the ICU.

PMID- 14710698
TI  - Toxicology in the critically ill patient.
AB  - Intoxications present in many forms including: known drug overdose or toxic
      exposure, illicit drug use, suicide attempt, accidental exposure, and chemical or
      biological terrorism. A high index of suspicion and familiarity with toxidromes
      can lead to early diagnosis and intervention in critically ill, poisoned
      patients. Despite a paucity of evidence-based information on the management of
      intoxicated patients, a rational and systematic approach can be life saving.

PMID- 14710697
TI  - Pharmacologic issues in the critically ill.
AB  - The pharmacotherapy of critically ill patients poses numerous challenges to the
      ICU team. Polypharmacy and alterations in drug disposition are common in the ICU;
      critically ill patients have limited physiologic reserve to deal with adverse
      drug events. Careful prescribing, based upon sound pharmacologic principles,
      decreases the potential for preventable adverse events and maximizes the
      opportunity for successful therapy. A systematic approach to reporting, analysis,
      and prevention of errors is a further step in our ultimate goal to provide
      optimal care for the vulnerable patients whom we support in our ICUs.

PMID- 14710699
TI  - Management of agitation in the intensive care unit.
AB  - Although the effective evaluation and management of agitated patients often
      receives less attention than other aspects of critical illness, it is among the
      most important and rewarding challenges that face critical care physicians. Key
      features of effective management include a thorough, organized search for
      potentially dangerous and correctable causes; a sound understanding of the
      pharmacology of analgesics and sedatives; and keeping a steady eye on appropriate
      management goals. In turn, the reward for excellent care will be shorter lengths
      of stay, more rapid liberation from mechanical ventilation, improved cognition,
      cost savings, and, perhaps, improved survival.

PMID- 14710700
TI  - Cognitive impairment in the intensive care unit.
AB  - Delirium is a frequent complication in older patients in the ICU and often
      persists beyond their ICU stay. Delirium in older persons in the ICU is a dynamic
      and complex process. There is a high prevalence of pre-existing cognitive
      impairment in patients who are admitted to the medical ICU. This pre-existing
      cognitive impairment is an important predisposing risk factor for the development
      of delirium during and after the ICU stay. Given the high rates of delirium in
      the ICU that range from 50% to 80% (see references [27, 28, 34]), future studies
      are urgently needed to examine risk factors for delirium in the ICU setting, such
      as examining the impact of psychoactive medication use on delirium rates and
      persistence in the ICU setting. Moreover, studies that examine the impact of
      delirium prevention in the ICU on rates of delirium, duration and persistence of
      delirium, and long-term cognitive and functional outcomes post-ICU stay are
      greatly needed.

PMID- 14710701
TI  - Guidelines in the intensive care unit.
AB  - The recent movement toward standardization of critical care practice is
      associated with a growth in the use of guidelines and protocols. Although
      complex, the process of guideline development, implementation, evaluation, and
      maintenance can be systematic. Guideline implementation can improve the processes
      and outcomes of care; however, guideline adherence represents a major challenge
      to their success. The quality of the growing number of practice guidelines in
      critical care is important to assess and several useful instruments are available
      for this purpose.

PMID- 14710702
TI  - Prognostication and intensive care unit outcome: the evolving role of scoring
      systems.
AB  - Prognostic scoring systems remain important in clinical practice. They enable us
      to characterize our patient populations with robust measures for predicted
      mortality. This allows us to audit our own experience in the context of
      institutional quality control measures and facilitates, albeit imperfectly,
      comparisons across units and patient populations. Practically, they provide an
      objective means to characterize case-mix and this helps to quantify resource
      needs when negotiating with hospital administrators for funding. Prognostic
      scores also help to stratify patient populations for research purposes. To be
      used accurately and effectively, one must have a good understanding of the
      limitations that are intrinsic to these prognostic systems. It is important to
      understand the details of their derivation and validation. The population of
      patients that is used to develop the models may not be relevant to your patient
      population. The model may have been derived several years before and may no
      longer reflect current practice patterns and treatment. These models may become
      obsolete over time. As with all scoring systems, there are potential problems
      with misclassification and more serious, systematic error, in data collection.
      One needs to rigorously adhere to guidelines about how these data are to be
      collected and processed; the persons who collect the data require regular updates
      and ongoing training. In their current form, the systems should not be used to
      prognosticate in individual patients, nor should they be used to define medical
      futility. The prognostic models should be viewed as being in evolution. Many
      patient and ICU characteristics that seem to have an important impact on
      mortality have yet to be incorporated into any of the current models. As an
      example, these may include the genetic characteristics of the patients and the
      ICU's organizational structure and process of care [51, 52]. Because the organ
      dysfunction measures are able to be obtained daily they give a much more complete
      understanding of the patient's entire ICU course as opposed to the initial 24
      hour period. Daily scores also help to capture the intensity of resource use and
      may help us gain a better understanding of what is truly ICU-acquired organ
      dysfunction. These measures may also be used for research to better characterize
      the natural history and course of a certain disease group or population. Also,
      they may be used in innovative ways to predict ICU mortality and post-ICU long
      term morbidity. These current and developing applications will help us to further
      understand the link between ICU severity of illness and long-term morbidity as we
      move beyond survival as the sole measure of ICU outcome.

PMID- 14710703
TI  - Improving care for patients dying in the intensive care unit.
AB  - It is impossible for ICU clinicians to avoid caring for dying patients and their
      families. For many, this is an extremely rewarding aspect of their clinical
      practice. There is ample evidence that there is room to improve the care of
      patients who are near death in the ICU. Despite the considerable holes in our
      knowledge about optimal care of dying critically ill patients, there is
      considerable agreement on the general principles of caring for these patients and
      about how to measure the outcomes of palliative care in the ICU. Practical
      approaches to improving the quality of end-of-life care exist and should be
      implemented.

PMID- 14710704
TI  - The evaluation and management of shock.
AB  - Shock is an emergency that requires continuous bedside evaluation, resuscitation,
      and re-evaluation. The initial bedside examination allows the clinician to
      determine whether the patient exhibits a clinical picture that is consistent with
      hypovolemic, cardiogenic, or vasodilatory shock. The primary survey dictates
      urgent initial resuscitation that usually consists of intubation, ventilation,
      and volume support. Vasoactive therapy is started when the patient is well volume
      resuscitated and consists of inotropic support for cardiogenic shock and pressor
      therapy for vasodilatory shock. The secondary survey is helpful in revealing the
      cause of shock and necessary to institute early definitive therapy. Early shock
      has a hemodynamic component, which is often easily reversed. Septic shock and
      prolonged shock from any cause has an inflammatory component, which is not easily
      reversed and leads to multiple-system organ failure (MSOF) and death. Success in
      treatment of shock depends on early recognition of shock and the rapid tempo of
      resuscitation of its hemodynamic component to prevent or minimize the
      inflammatory component.

PMID- 14710705
TI  - Supporting high school students to engage in recreational activities with peers.
AB  - The authors investigated the effects of an intervention package to support five
      high school students with extensive support-needs to initiate and engage in
      recreational activities with general-education peers in their physical education
      classes. The intervention components were (a) assessing participants'
      recreational activity goals, (b) teaching self-prompting using a picture book,
      (c) programming common stimuli, and (d) asking participants to assess daily
      performance and evaluate daily goal achievement. The intervention was associated
      with increases in participants' initiation of and engagement in recreational
      activities with general-education peers, as well as increases in ratings of
      quality of interaction. In addition, participants typically assessed with
      accuracy their performance of recreational activities and whether they had
      achieved their recreational goals. Findings are discussed with respect to future
      research and practice.

PMID- 14710706
TI  - The use of a positive procedure to increase engagement on-task and decrease
      challenging behavior.
AB  - The exhibition of stereotypic and self-injurious behavior (SIB) combined with a
      lack of work engagement makes it very difficult to place a person with severe
      disabilities in an integrated work environment. The purpose of this research was
      to examine use of a positive procedure to increase engagement on-task and reduce
      self-injurious slapping and stereotypic clothes manipulation by a 46-year-old man
      with severe disabilities. A single-subject research design was used to examine
      the effects of the combined DRA-DRO (differential reinforcement of alternative
      behavior-differential reinforcement of other behavior) procedure in fostering
      more appropriate behavior. Following 30 years of institutionalization, the man
      was successfully integrated into community-based employment.

PMID- 14710707
TI  - Behavioral interventions to reduce the pica of persons with developmental
      disabilities.
AB  - The consumption of nonfood items (i.e., pica) frequently occurs in persons with
      developmental disabilities. Pica may result in the puncture or blockage of the
      digestive tract, infestation by gastrointestinal parasites, and can interfere
      with an individual's daily learning, occupational performance, and quality of
      life. Twenty-six published studies have examined the efficacy of behavioral
      intervention packages (e.g., differential reinforcement of other behavior,
      noncontingent attention, or overcorrection) on the pica of persons with
      developmental disabilities. This article reviews those studies and discusses the
      effectiveness, generality, and acceptability of the various intervention packages
      used to reduce pica. Additionally, this article highlights the recent clinical
      advancements that have been made in the treatment of the pica of persons with
      developmental disabilities.

PMID- 14710708
TI  - Cognitive behavioral treatment for older adults with generalized anxiety
      disorder. A therapist manual for primary care settings.
AB  - At least four academic clinical trials have demonstrated the utility of cognitive
      behavior therapy (CBT) for older adults with generalized anxiety disorder (GAD).
      These data may not generalize, however, to more heterogeneous and functionally
      impaired patients and the medical settings in which they typically receive care.
      A recent pilot project suggested the potential benefits of a new version of CBT
      for GAD among older patients in primary care. The manual developed and tested in
      this pilot project is presented here. Treatment components include motivation and
      education, relaxation skills, cognitive therapy, problem-solving-skills training,
      exposure exercises, and sleep-management-skills training. Procedures are designed
      to be administered flexibly to maximize attention to individual patient needs.
      Examples of session summaries, patient handouts, and homework forms are provided.

PMID- 14710709
TI  - Functional analysis of erratic body movement maintained by visual stimulation.
      Incorporating conjugate reinforcement into a paired-stimulus preference
      assessment.
AB  - A concurrent-operants design was used to analyze the repetitive behavior of
      observing reflective surfaces while simultaneously engaging in erratic gross
      motor body movements (EBMs) exhibited by a young boy diagnosed with autism. The
      assessment involved an evaluation of preference for controlled (i.e., the
      participant controlled the visual activity on a TV screen) versus uncontrolled
      (i.e., the participant viewed a previously recorded tape from the controlled
      condition) TV footage of his EBMs. The analysis indicated that both observing and
      EBMs were maintained by the direct correspondence between the body movements and
      the visual stimulation they produced when controlled by the participant. Thus,
      the EBMs appeared to be maintained on a conjugate schedule of reinforcement.

PMID- 14710710
TI  - Smoking cessation for high school students. Impact evaluation of a novel program.
AB  - This pilot study was designed to evaluate the feasibility and the impact of a
      smoking-cessation program that would meet the specific needs of high school
      students. Feedback from focus groups conducted with adolescent smokers at a
      Connecticut high school was used to develop a tailored intervention. Intervention
      components included commonly used behavioral strategies, with additional options
      to assist students to quit smoking, including use of bupropion, concomitant
      support for parent smoking cessation, stress management, and physician
      counseling. On completion, 20 of the 22 enrolled students remained committed to
      quitting. Twenty-seven percent of students quit smoking and 69% of those who
      continued to smoke reduced the number of cigarettes smoked per day by an average
      of 13. Providing additional options to students and additional support for
      concomitant parental cessation may enhance the appeal of adolescent smoking
      cessation programs. Further investigation into efficacy of bupropion use for
      adolescent cessation is warranted.

PMID- 14710711
TI  - The functional profiles of school refusal behavior. Diagnostic aspects.
AB  - School refusal behavior is a common problem seen by mental health professionals
      and by educators but little consensus is available as to its classification,
      assessment, and treatment. This study assessed 143 youth with primary school
      refusal behavior and their parents to examine diagnoses that are most commonly
      associated with proposed functions of school refusal behavior. As expected,
      results indicated that great heterogeneity in diagnoses marks this population. In
      general, anxiety-related diagnoses were associated more with negatively
      reinforced school refusal behavior; separation anxiety disorder was associated
      more with attention-seeking behavior; and oppositional defiant disorder and
      conduct disorder were associated more with pursuit of tangible reinforcement
      outside of school. These results are discussed within the context of
      classification, assessment, and treatment of this population.

PMID- 14710712
TI  - [Antifungal treatment of systemic mycoses, new molecules and new concepts on in
      vitro tests. 7th National Congress of the Spanish Society of Chemotherapy].

PMID- 14710713
TI  - Filling in the blanks.

PMID- 14710714
TI  - [Multiple hamartoma in the right breast with bilateral accessory breasts: report
      of one case].

PMID- 14710715
TI  - Finding a way forward in dementia care.

PMID- 14710716
TI  - Diagnostic strategies in CADASIL.

PMID- 14710717
TI  - New low-dose estrogen approved for prevention of postmenopausal osteoporosis.

PMID- 14710718
TI  - Guideline for hand hygiene in  healthcare settings.

PMID- 14710719
TI  - The research-quality assessment connection. 1987.

PMID- 14710720
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14710721
TI  - Report and abstracts of the 12th Annual Meeting of the European Neuropeptide
      Club. Olsztyn, Poland, May 22-25, 2002.

PMID- 14710722
TI  - Haloperidol reduces IgG immunoreactivity in the rat brain.
AB  - Immunohistochemical staining with non-specific IgG reliably labels a subset of
      neurons in both rat and human brain, overlapping the distribution of cortico
      limbic D2 receptors (D2R). We used haloperidol to up-regulate rat D2R to observe
      any associated changes in IgG immunostaining. Rats were treated with haloperidol
      or vehicle for 30 d. Some rats were assessed for D2R up-regulation with
      apomorphine. The remaining rats were processed immunohistochemically and IgG
      stained cells counted and statistically analysed in three cortico-limbic areas.
      Other brain regions were surveyed qualitatively. Positive (anti-glial fibrillary
      acidic protein or anti-tyrosine hydroxylase staining) and negative (antisera
      omitted) controls were performed on adjacent sections. Haloperidol dramatically
      the IgG staining areas quantified with all surveyed regions significantly
      decreased. Positive control staining was robust, ruling out generalized
      immunoreactivity reduction. These observations raise the possibility of an
      immunological effect of haloperidol in the brain. The identification and function
      of these IgG-labelled sites may have useful implications for psychosis.

PMID- 14710723
TI  - Development of wet environment TEM (wet-ETEM) for in situ studies of liquid
      catalyst reactions on the nanoscale.
AB  - We present the development of in situ wet environmental transmission electron
      microscopy (wet-ETEM) for direct probing of controlled liquid-catalyst reactions
      at operating temperatures on the nanoscale. The first nanoscale imaging and
      electron diffraction of dynamic liquid hydrogenation and polymerization reactions
      in the manufacture of polyamides reported here opens up new opportunities for
      high resolution studies of a wide range of solution-solid and solution-gas-solid
      reactions in the chemical and biological sciences.

PMID- 14710724
TI  - Attitude is a line item.

PMID- 14710725
TI  - NAHC cost report database reveals PEP, outlier episode losses.

PMID- 14710726
TI  - Seasonal adjustment.

PMID- 14710727
TI  - Presidential address given at the 69th annual meeting of the American Mosquito
      Control Association, March 2003. AMCA and you in 2002-2003: is the Clean Water
      Act swamping mosquito control efforts against West Nile virus?

PMID- 14710728
TI  - Geographical distribution of Anopheles darlingi in the Amazon Basin region of
      Peru.
AB  - Malaria has reemerged as a significant public health disease threat in Peru,
      especially within the Amazon Basin region. This resurgence of human cases caused
      by infection with Plasmodium falciparum and Plasmodium vivax is thought to be
      associated with the spread of Anopheles darlingi, the principal South American
      malaria vector, into new areas of the Amazon Basin. However, comprehensive
      studies of the distribution for this species have not been conducted in Peru for
      several years, nor are historical accounts accurate enough to determine if An.
      darlingi was actually present and not collected or misidentified. Therefore, the
      objective of this study is to define the distribution of An. darlingi as well as
      obtain data on distribution and abundance of other Anopheles species in this
      region. Mosquitoes were collected during 2001 in the Departments of Loreto and
      Ucayali, the two largest Amazonian Departments of Peru. A total of 60,585
      specimens representing 12 species of the subgenera Nyssorhynchus and Anopheles
      were collected at 82 (88.2%) of 93 collecting sites. The majority of mosquitoes
      obtained were identified as An. benarrochi, comprising 70.7% of mosquitoes
      collected, followed by An. darlingi (24.0%), Anopheles mattogrosensis (2.4%), and
      Anopheles triannulatus (1.5%). Anopheles darlingi was collected from 48.8% of
      sites, indicating that this species is established throughout central Loreto,
      including further west in the Amazon Basin than previously reported. These data
      suggest that this species is now found in areas of the Amazon Basin region where
      it has not been previously reported.

PMID- 14710729
TI  - Has Aedes albopictus established in California?
AB  - Significant numbers of the Asian tiger mosquito, Aedes albopictus, were detected
      on the west coast of the USA in mid-June 2001, in containerized oceanic shipments
      of "lucky bamboo" (Dracaena spp.) originating from South China. Wholesale
      nurseries in California importing large quantities of lucky bamboo became the
      focal points of infestation. Greater Los Angeles County Vector Control District
      immediately implemented an adulticiding protocol at the Los Angeles/Long Beach
      Harbors, followed by larviciding soon after the shipment was delivered to the
      wholesale nursery. Intensive surveys are currently being conducted above ground
      and in the underground storm drain systems using battery-operated CDC/CO2-baited
      light traps and ovitraps, both enhanced with an attractant (water rinse of tiger
      shrimps), to determine extent of infestation and perhaps establishment of Ae.
      albopictus locally.

PMID- 14710730
TI  - Introduction and potential establishment of Aedes albopictus in California in
      2001.
AB  - Aedes albopictus was discovered in Los Angeles, California, in June 2001 in a
      maritime cargo container from China containing a shipment of a commercial plant
      product known as "Lucky Bamboo" (Dracaena spp.). To keep the plants alive during
      the ocean transit, they were shipped in 5-8 cm of water, providing an excellent
      habitat for Ae. albopictus. Mosquito infestations were subsequently detected at
      15 nursery distributors of Dracaena in 2 northern and 4 southern California
      counties. The distribution of the Ae. albopictus infestations was limited to the
      vicinity of those nursery distributors with documented infestations. Infestations
      persisted for more than 5 months near some of the nurseries, and eggs were found
      in ovitraps until mid-November 2001 up to 1,000 m from the original infestation
      sites. Overwintering Ae. albopictus populations were discovered in April, July,
      and August 2002 at original infestation sites in Chino, San Bernardino County,
      and Monterey Park and Rowland Heights, Los Angeles County, respectively.
      Specimens were found at some sites of overwintering populations until October
      2002.

PMID- 14710731
TI  - Description of Bruceharrisonius, a new subgenus of Ochlerotatus, and a
      redescription of its type species Oc. (Brh.) greenii.
AB  - The new subgenus Bruceharrisonius is described and principal features of all
      known stages are provided for separating it from other subgenera of genus
      Ochlerotatus. The female, male, female and male genitalia, pupa, and 4th-stage
      larva of the type species, Oc. greenii, are described in detail. Eight species
      (Oc. alektorovi, Oc. aureostriatus, Oc. doonii, Oc. christophersi, Oc. greenii,
      Oc. hurlbuti, Oc. okinawanus, and Oc. taiwanus) currently are recognized in the
      subgenus.

PMID- 14710732
TI  - Polymerase chain reaction assay identifies North American members of the Culex
      pipiens complex based on nucleotide sequence differences in the
      acetylcholinesterase gene Ace.2.
AB  - Nucleotide sequence differences in the acetylcholinesterase gene Ace.2 were used
      to develop an assay to distinguish among North American mosquitoes of the Culex
      pipiens complex. Taxon-specific polymerase chain reaction primers based on
      sequence differences within intron 2 of Ace.2 distinguish among the sibling
      species Cx. pipiens Linneaus and Cx. quinquefasciatus Say and their F1 hybrids.
      This assay may be used to confirm the species composition of mosquito pools,
      identify individual specimens collected in arbovirus surveillance programs and
      other mosquito studies, and define zones of hybridization.

PMID- 14710733
TI  - Genetic relationships among populations of Aedes aegypti in Taiwan by using
      phenotypic and random amplified DNA-polymerase chain reaction markers.
AB  - An analysis of gene flow was conducted among collections of Aedes aegypti from 7
      localities along the southwestern and southeastern coasts in Taiwan. Markers
      include 7 types of scaling patterns and 23 random amplified polymorphic DNA
      (RAPD) loci amplified by the polymerase chain reaction. Differences in scaling
      pattern and in the frequencies of RAPD markers were detected among populations
      and cluster analyses revealed 2 main groups on each side of the Central Mountain
      Range. Regression analysis of geographic distances and pairwise F(ST) values
      estimated from RAPD markers showed that southwestern populations are isolated by
      distance and that populations within 15 km are panmictic. This is a shorter
      distance than detected among collections of Ae. aegypti in similar published
      studies from Mexico and Argentina.

PMID- 14710734
TI  - The species composition and seasonal distribution of mosquitoes in vernal pools
      in suburban Montreal, Quebec.
AB  - A study was conducted in the spring and summer of 1998 to determine the
      invertebrate community in vernal pools on the western portion of the Island of
      Montreal. This paper examines the mosquitoes (Diptera: Culicidae) found in 10
      pools. Fifteen species in 4 genera (Aedes, Anopheles, Culex, and Ochlerotatus)
      were collected and the seasonal distribution of each species was determined.
      Ochlerotatus stimulans was the most abundant species. Two peaks occurred in
      larval abundance, in late April and early July. Larvae were more abundant in the
      spring; larval density was higher later in the summer. The abundance of
      mosquitoes in these pools was similar to those found in remote regions of the
      province.

PMID- 14710735
TI  - Age-dependent bloodfeeding of Aedes aegypti and Aedes albopictus on artificial
      and living hosts.
AB  - In order to quantify age-dependent acquisition of a bloodmeal, we compared
      bloodfeeding patterns of Aedes aegypti and Aedes albopictus starting from the
      time of first responsiveness to a bloodmeal up to 15 days postemergence. In
      separate experiments, cohorts of Ae. aegypti and Ae. albopictus of known age were
      offered their first bloodmeal from a silicon-membrane system or a restrained
      chicken. For cohorts ranging from 3 to 15 days old, the proportions feeding were
      significantly affected by species, age, feeding protocol, and the age x feeding
      protocol interaction. For both feeding protocols, a higher proportion of Ae.
      aegypti than Ae. albopictus, on average, consumed blood. Regressions of
      proportion feeding versus age indicated significantly positive slopes for Ae.
      albopictus and Ae. aegypti on the membrane system, and no significant
      relationship was observed for either species on the restrained chicken.
      Additionally, slopes for Aedes, as a group, fed on the membrane system were
      significantly different from those fed on the living host. For both Aedes species
      fed on the restrained chicken and for Ae. aegypti fed on the membrane system, the
      proportions feeding exhibited periodic patterns, with peaks approximately 2 days
      apart, suggesting possible control by endogenous rhythms.

PMID- 14710736
TI  - An easy field method for estimating the abundance of culicid larval instars.
AB  - A new method is proposed that avoids manual counting of mosquito larvae in order
      to estimate larval abundance in the field. This method is based on the visual
      comparison between abundance, in a standardized sampling tray (called an abacus),
      with 5 (abacus 5) or 10 (abacus 10) diagrammatically prepared abundance classes.
      Accuracy under laboratory and field conditions and individual bias have been
      evaluated and both abaci provide a reliable estimation of abundance in both
      conditions. There is no individual bias, whether people are familiar or not with
      its use. They could also be used for a quick estimation of larval treatment
      effectiveness, for the study of population dynamics and spatial distribution.

PMID- 14710737
TI  - The impact of wetland vegetation drying time on abundance of mosquitoes and other
      invertebrates.
AB  - Vegetation management for constructed treatment wetlands often involves knocking
      down emergent vegetation with heavy equipment and inundating the dead vegetation
      after a period of drying. Such practices create favorable conditions for larval
      mosquitoes. We studied the relationship between length of the drying period for
      an emergent macrophyte, Typha sp., and the abundance of aquatic invertebrates in
      replicated 0.18-m3 wading pools. The mosquito, Culex tarsalis, was significantly
      more abundant in pools containing vegetation aged for 2 wk before inundation
      compared to pools containing vegetation aged 5 wk, freshly cut vegetation, or
      without vegetation. Potential larval mosquito food resources (particles between 2
      and 61 microm in equivalent spherical diameter) in the 2-wk aging treatment did
      not differ significantly from the other treatments during the 5-wk experiment.
      The abundance of other larval culicids, nonculicine Diptera, and potential
      mosquito predators (i.e., Dytiscidae and Aeshnidae) did not differ significantly
      among the vegetation aging treatments.

PMID- 14710738
TI  - Artificial bloodfeeding of Anopheles sacharovi on a membrane apparatus.
AB  - Anopheles sacharovi, the main human malaria vector in Turkey, has been maintained
      in our laboratory by feeding on anesthetized rabbits for about 20 years but it is
      a difficult species to colonize and bloodfeed. To eliminate the need for keeping
      and using live rabbits to supply blood meals, artificial bloodfeeding methods
      with suitable membrane apparatus were investigated. The feeding apparatus
      designed by the World Health Organization and 3 other types designed by us (for
      feeding on preserved human blood) were tested. Artificial membranes (latex and
      paraffin film) and locally produced and dried calf intestine were used. The calf
      intestine membrane gave the best feeding results and a modified apparatus
      designated type III was the most successful. This apparatus was preferable for
      the artificial feeding of An. sacharovi because it has a small reservoir, is easy
      to use, is adaptable to different feeding conditions, and supports reasonably
      high bloodfeeding rates 44.4-50.5% as compared to 35% on live rabbits.

PMID- 14710739
TI  - Blood-meal analysis for anopheline mosquitoes sampled along the Kenyan coast.
AB  - A total of 1,480 Anopheles gambiae sensu lato and 439 An. funestus, collected
      from 30 sites along the Kenyan coast, were tested by direct enzyme-linked
      immunosorbent assay (ELISA) for blood-meal identification. Overall, the enzyme
      linked immunosorbent assay (ELISA) identified 92 and 87% of the samples tested in
      An. gambiae s.l. and An. funestus, respectively. Of these, human IgG was detected
      in 98.97% (n = 1,347) of An. gambiae s.l. and 99.48% (n = 379) of An. funestus.
      Only 14 (1.03%) of the An. gambiae s.l. had fed on other vertebrate hosts tested,
      which were bovines, chickens, and goats. Additionally, only 2 An. funestus had
      fed on goats. In all the 28 sites that had bloodfed mosquitoes, An. gambiae s.l.
      had a human blood index greater than 0.9. Twenty-five of these sites had a human
      blood index greater than 0.9 for An. funestus, while the other 3 sites had no
      bloodfed mosquitoes. The An. gambiae s.l. were tested by polymerase chain
      reaction (PCR) for species identification. A total of 338 were An. gambiae s.s.,
      79 were An. arabiensis, and 12 were An. merus. The human blood index was 0.96,
      0.91, and 1.0 for An. gambiae s.s., An. arabiensis, and An. merus, respectively.
      The Plasmodium falciparum sporozoite infection rates were 6.2% for species in the
      An. gambiae complex and 3.7% for An. funestus. These results emphasize that An.
      funestus and members of the An. gambiae complex on the Kenyan coast are highly
      anthropophilic, with nearly all specimens feeding on humans during every blood
      meal. The results further demonstrated active transmission of P. falciparum
      sporozoites by the primary vector species. This study suggests that the use of
      insecticide-treated nets will be effective for controlling biting mosquitoes
      inside houses along the coast of Kenya.

PMID- 14710740
TI  - Expanded polystyrene (EPS) floats for surveillance of Ochlerotatus japonicus.
AB  - Blocks of expanded polystyrene (EPS) were placed in a variety of habitats to
      investigate their potential as an egg-collection device for container-dwelling
      Aedes and Ochlerotatus species. Eggs from Ochlerotatus japonicus, Oc.
      triseriatus, Oc. hendersoni, and Aedes albopictus were collected with EPS floats.
      The float provides an inexpensive, low-maintenance alternative to the Centers for
      Disease Control ovitrap for sampling container-dwelling mosquito species that are
      important vectors of disease. Eggs collected on the floats have many potential
      applications, including use in routine population surveillance; detection of Oc.
      japonicus, Ae. albopictus, and other container-dwelling species in new areas;
      species distribution studies; natural transovarial transmission studies;
      ovipositional studies; collection of local field populations for insecticide
      resistance assays; assessment of adulticiding efficacy; and establishment of new
      laboratory colonies.

PMID- 14710741
TI  - Spatiotemporal oviposition and habitat preferences of Ochlerotatus triseriatus
      and Aedes albopictus in an emerging focus of La Crosse virus.
AB  - The number of cases of encephalitis caused by La Crosse virus recently has
      increased in southwestern Virginia counties. This article presents results of a
      study conducted from May to September 2000 in Wise County, VA, that examined the
      area-wide oviposition activity and habitat preferences of Ochlerotatus
      triseriatus and Aedes albopictus, potential vectors of La Crosse virus in the
      region. Data from 490 ovitrap collections made throughout the county showed that
      mean oviposition activity throughout the study was higher for Oc. triseriatus
      (20.4 eggs/trap-day) than for Ae. albopictus (3.7 eggs/trap-day). The 2 species
      also had distinct habitat preferences for oviposition, with Oc. triseriatus
      favoring forested habitats and Ae. albopictus favoring urban/residential
      habitats. A landcover map of 6 habitat types derived from Landsat satellite
      imagery of the county showed that 63% of the county was forested and 18% was
      urban/residential. A Bayesian decision-rule model that incorporated the ovitrap
      data and landcover map was moderately successful at predicting the occurrence of
      high oviposition activity and abundance of the 2 species. The predictions
      reflected seasonal and spatial fluctuations in oviposition activity, with
      accuracies between 55 and 79% for Oc. triseriatus and 70 and 94% for Ae.
      albopictus. Kappa (K), a measure of the predictive power of the model, varied
      from poor (K < 0.4) to good (0.4 < K < 0.75) for both species, and was highest
      during periods when actual egg abundance was high. This suggests that the
      predictions were most accurate during periods when the risk for La Crosse virus
      transmission is greatest. Limitations and suggestions for improving the model are
      discussed.

PMID- 14710742
TI  - Flavivirus isolations from mosquitoes collected from western Cape York Peninsula,
      Australia, 1999-2000.
AB  - After the 1st appearance of Japanese encephalitis virus (JE) on mainland
      Australia in 1998, a study was undertaken to investigate whether JE had become
      established in enzootic transmission cycles on western Cape York Peninsula. Adult
      mosquitoes were collected during the late wet season from Kowanyama and
      Pormpuraaw in April 1999, and Pormpuraaw and Barr's Yard in April 2000. Despite
      processing 269,270 mosquitoes for virus isolation, no isolates of JE were
      obtained. However, other flaviviruses comprising Murray Valley encephalitis
      virus, Kunjin virus, Alfuy virus, and Kokobera virus (KOK) were isolated.
      Isolates of the alphaviruses Ross River virus, Barmah Forest virus (BF), and
      Sindbis virus (SIN) also were obtained. The majority (88%) of isolates were from
      members of the Culex sitiens subgroup. Single isolates of KOK, BF, and SIN were
      obtained from Ochlerotatus vigilax, Oc. normanensis, and Anopheles bancroftii,
      respectively. The isolations of flaviviruses during the late wet season indicate
      that conditions were suitable for flavivirus activity in the area. No evidence
      was found to suggest that JE has become established in enzootic transmission
      cycles on western Cape York, although study sites and field trips were limited.

PMID- 14710743
TI  - Laboratory evaluation of 18 repellent compounds as oviposition deterrents of
      Aedes albopictus and as larvicides of Aedes aegypti, Anopheles quadrimaculatus,
      and Culex quinquefasciatus.
AB  - Among 18 experimental skin repellent compounds tested at five concentrations in
      the laboratory as oviposition deterrents against Aedes albopictus. 12 compounds
      showed significant activity, with median effective dose values ranging from 0.005
      to 0.052%. The test compounds also were evaluated in the laboratory as larvicides
      against laboratory-reared 4th instars of Aedes aegypti, Anopheles
      quadrimaculatus, and Culex quinquefasciatus with the same concentrations employed
      for the oviposition deterrency tests against Ae. albopictus. Larval mortality
      data at 24 and 48 h after treatment indicated that 12 test repellents caused
      larval mortalities in the range of 67 to 100% against An. quadrimaculatus, 10
      compounds induced 55-100% larval mortalities of Ae. aegypti, whereas larval
      mortality caused by 9 compounds ranged from 74 to 100% against Cx.
      quinquefasciatus. These mortality data did not fit the linear model of the
      statistical analysis. However, multiway analysis of variance of these data showed
      that the repellent compounds, concentrations used, species of mosquitoes, and
      exposure times affect the degree of larval mortalities.

PMID- 14710744
TI  - Laboratory efficacy tests for fungal metabolites of Chrysosporium tropicum
      against Culex quinquefasciatus.
AB  - Efficacy of fungal metabolites of Chrysosporium tropicum was evaluated against
      Culex quinquefasciatus larvae in the laboratory to determine their larvicidal
      activity at 6 concentrations, with a mortality range of 10-95%. Efficacy of C.
      tropicum was analyzed by probit analysis procedures. The LC50 (concentration
      lethal to 50% of the population) values were 38.9, 63.7, 79.0, and 122.6
      microl/ml for the 1st, 2nd, 3rd, and 4th instars, respectively. The LC50 values
      were 79.5, 95.6, 136.9, and 174.5 microl/ml against the 1st-, 2nd-, 3rd-, and 4th
      stage larvae, respectively. Lethal concentrations of fungal metabolites were
      significantly different among the 4 instars. The 1st-stage larvae were most
      susceptible, whereas 4th instars were least susceptible to C. tropicum
      metabolites. The larvicidal potential of C. tropicum metabolites warrants field
      trials against various species of mosquitoes.

PMID- 14710745
TI  - Laboratory and field evaluations of novaluron, a new insect growth regulator
      (IGR), against Culex mosquitoes.
AB  - Limited laboratory and field studies have indicated that the insect growth
      regulator (IGR) novaluron exhibits good activity against larvae of pest species
      in the orders Coleoptera, Hemiptera (suborder Heteroptera), and Lepidoptera by
      both ingestion and contact. We completed laboratory and field studies to evaluate
      activity and efficacy of novaluron against Culex mosquitoes. In laboratory
      studies, novaluron was highly active against Cx. quinquefasciatus, as indicated
      by low levels of inhibition of emergency (IE), at the 50% level, IE50 (0.159 ppb
      for 2nd-stage larvae and 0.118 ppb for 4th-stage larvae) and IE90, at the 90%
      level, (0.604 ppb for 2nd-stage larvae and 0.595 ppb for 4th-stage larvae). In
      outdoor microcosm and mesocosm studies against natural populations, novaluron
      yielded excellent control of immature Culex mosquitoes for up to 14 days at 1.25,
      2.5, and 5 ppb in microcosms, and for up to 7 days at the dosages of 1, 5, and 10
      mg/m2 in mesocosms. Based on qualitative observations, novaluron seemed to have a
      favorable margin of safety for nontarget aquatic invertebrates cohabiting with
      mosquito larvae. Further large-scale field studies are warranted to evaluate
      initial efficacy and longevity of novaluron against various mosquito species, as
      well as its safety for nontarget biota.

PMID- 14710746
TI  - Susceptibility of Italian populations of Aedes albopictus to temephos and to
      other insecticides.
AB  - We evaluated larval and adult susceptibility to 5 insecticides commonly used for
      control of Aedes albopictus, by using 15 field-collected populations from
      northern and central Italy, and we compared these data, collected in 2002, with
      those from evaluations conducted in 1992-93, 1996, and 1998-99. Larvae were
      tested for susceptibility to temephos and to the conventional diagnostic dosages
      of chlorpyrifos and fenthion proposed by the World Health Organization for Aedes
      aegypti. Adults were exposed to the diagnostic dosages of deltamethrin and
      permethrin. Overall, all of the populations tested in 2002 were still susceptible
      to temephos: median lethal concentration (LC50) values ranged from 0.0026 to
      0.0085 mg/liter, and LC99 values ranged from 0.0093 to 0.023 mg/liter. These
      populations were also fully susceptible to chlorpyrifos and fenthion, and adults
      were susceptible to deltamethrin and permethrin. When comparing these data with
      those from previous evaluations, we observed a slight yet progressive increase in
      the LC50 and LC99 values of susceptibility to temephos, and these values are
      approaching the diagnostic dosage of 0.02 mg/liter proposed for Ae. aegypti.
      However, the implications of these findings need to be considered in light of the
      results of previous studies that have shown that larval Ae. albopictus are less
      susceptible than Ae. aegypti to organophosphate insecticides.

PMID- 14710747
TI  - A semifield evaluation of Vectobac DT (ABG-6499), a new formulation of Bacillus
      thuringiensis israelensis for control of Aedes albopictus.
AB  - We evaluated the effectiveness and duration of effectiveness of a new formulation
      of Bacillus thuringiensis var. israelensis (Bti) for control of larval Aedes
      albopictus. The product tested was Vectobac DT (ABG-6499), a Bti tablet
      formulation containing 3.4% of active ingredient (3,400 ITU/mg) supplied by SCAE
      Valent BioSciences Italy S.r.l. The study was conducted at the Botanical Garden
      of the University of Rome "La Sapienza" between June and September 2002, the most
      favorable season for the development of Ae. albopictus in Italy. Black 20-liter
      plastic buckets containing water and an organic substrate were used as
      experimental breeding sites. The number of larvae in these buckets was estimated
      weekly, and positive buckets were treated with the recommended dose of the
      larvicide. The results showed that Vectobac DT induced 100% larval mortality
      after 24 h in all experimental breeding sites during the entire study period.
      Nonetheless, in most cases, the larvicidal activity only lasted about 48 h; thus,
      effective mosquito control would require that treatment be performed every 8-10
      days in this habitat.

PMID- 14710748
TI  - Effects of the agricultural insecticide lambda-cyhalothrin (Warrior) on
      mosquitofish (Gambusia affinis).
AB  - Because agricultural insecticides have potential to disrupt biological control of
      mosquitoes, we quantified whether an insecticide used in rice fields causes
      mortality of mosquitofish. Laboratory studies have shown that lambda-cyhalothrin
      (Warrior) is toxic to fish; however, some studies report low field toxicities of
      pyrethroids to fish because they degrade rapidly and adsorb to soil. We tested
      whether Warrior kills mosquitofish under field conditions. Replicated enclosures
      in a rice field were either sprayed with Warrior at 5.8 g active ingredient/ha or
      were untreated. Mosquitofish were either added before the spray, or 7 days later.
      Of those added before the spray, none survived. Most fish added 7 days later
      survived.

PMID- 14710749
TI  - Transfer of Heizmannia thelmae from subgenus Mattinglyia to subgenus Heizmannia
      of genus Heizmannia and new characters for separating the two subgenera.
AB  - Heizmannia thelmae is formally transferred from subgenus Mattinglyia and assigned
      to subgenus Heizmannia. Rationale for this action is provided. New characters of
      the adults, female genitalia, and pupae are listed for separating the 2 subgenera
      of Heizmannia.

PMID- 14710750
TI  - Anopheles (Cellia) carnevalei in Equatorial Guinea (West-Central Africa).
AB  - Anopheles (Cellia) carnevalei is described in the mainland region (Rio Muni) of
      Equatorial Guinea. Anophelines collected were identical to An. nili with
      exception of some morphological characters found in wings, head, and legs.

PMID- 14710751
TI  - First record of Aedes albopictus from Trinidad, West Indies.
AB  - This is the 1st report of the occurrence of Aedes albopictus in Trinidad, West
      Indies. Eggs collected in 2 ovitraps, 1 in November and 1 in December 2002, were
      hatched and reared to adults at the Insect Vector Control Division laboratory.
      Three female Ae. albopictus emerged, whereas 6 females were collected by human
      bait collections. The implications of these findings are discussed.

PMID- 14710752
TI  - Sensitivity of the VecTest antigen assay for eastern equine encephalitis and
      western equine encephalitis viruses.
AB  - VecTest assays for detecting eastern equine encephalitis virus (EEE) and western
      equine encephalitis virus (WEE) antigen in mosquito pools were evaluated to
      determine their sensitivity and specificity by using a range of EEE, WEE, St.
      Louis encephalitis virus (SLE), and West Nile virus (WN) dilutions as well as
      individual and pooled mosquitoes containing EEE or WEE. The EEE test produced
      reliable positive results with samples containing > or = 5.3 log10 plaque-forming
      units (PFU) of EEE/ml, and the WEE test produced reliable positive results with
      samples containing > or = 4.7 log10 PFU WEE/ml. Both assays detected the
      respective viral antigens in single virus-positive mosquitoes and in pools
      containing a single positive mosquito and 49 negative specimens. The SLE and WN
      assays also contained on the dipsticks accurately detected their respective
      viruses. No evidence was found of cross reaction or false positives in any of the
      tests. The VecTest assays were less sensitive than the EEE- and WEE-specific
      TaqMan reverse transcriptase polymerase chain reaction and Vero cell plaque
      assay, but appear to be useful for detecting arboviruses in mosquito-based
      arbovirus surveillance programs.

PMID- 14710753
TI  - Evaluation of carbon dioxide- and 1-octen-3-ol-baited Centers for Disease Control
      Fay-Prince traps to collect Aedes albopictus.
AB  - During the summer of 2001, field studies were performed to evaluate the effects
      of carbon dioxide (CO2) and 1-octen-3-ol (octenol) on the ability to collect
      Aedes albopictus with Centers for Disease Control (CDC) Fay-Prince traps. Results
      from these studies indicated that Ae. albopictus is significantly more attracted
      to CO2- or CO2 + octenol-baited CDC Fay-Prince traps than unbaited or octenol
      baited traps. However, the difference between the responses to CO2 and CO2 +
      octenol was not statistically different, indicating that CO2 is driving the
      response of Ae. albopictus to CDC Fay-Prince traps.

PMID- 14710754
TI  - Integrated vector management guidelines for adult mosquitoes.
AB  - A written document was developed to clarify the District's adult mosquito
      management tactics to other interested individuals and agencies. The program
      described consists of 7 discrete components: 1) initiation criteria, 2) treatment
      area delineation, 3) agricultural and land-use practices, 4) meteorological
      conditions, 5) continuance criteria, 6) termination criteria, and 7) factors
      influencing implementation. The guidelines were adopted as policy by the
      District's Board of Trustees in 1998 and have been implemented in each of the
      last 5 years. The adult mosquito population is monitored with 6 Mosquito Magnets
      traps strategically located in the rice culture areas. Samples are collected
      daily and laboratory technicians notify the Adulticide/Airplane Coordinator of
      collection results before 1:00 p.m.

PMID- 14710755
TI  - Mosquito systematics: from organisms to molecules--a tribute to Kenneth L.
      Knight.
AB  - The person, career, and achievements of Kenneth Lee Knight are portrayed. Ken was
      a gentlemanly naval officer, scientist, and scholar who made substantial
      contributions to medical entomology and the systematics of mosquitoes. His
      interest in the history of mosquito taxonomy serves as the backdrop for reviewing
      the development of mosquito systematics from an organismal to molecular
      perspective. Benefits and problems associated with the application of modern
      methods used in mosquito systematics research are pointed out.

PMID- 14710756
TI  - Cryptobia (Trypanoplasma) salmositica and salmonid cryptobiosis.
AB  - Salmonid cryptobiosis is caused by Cryptobia (Trypanoplasma) salmositica. The
      haemoflagellate has been reported from all species of Pacific Oncorhynchus spp.
      on the west coast of North America. It is normally transmitted by the freshwater
      leech, Piscicola salmositica, in streams and rivers, and sculpins, Cottus spp.,
      are considered important reservoir hosts. The pathogen can also survive on the
      body surface of fish because it has a contractile vacuole to osmoregulate when
      the fish is in fresh water. This allows for direct transmission between fish,
      especially in aquaculture facilities. The parasite divides rapidly by binary
      fission in the blood to cause disease, the severity of which is directly related
      to parasitaemia. Cryptobia salmositica has a mitochondrium and it normally
      undergoes aerobic respiration; however, if its mitochondrium is damaged it will
      switch to glycolysis. Its glycolytic enzymes and catalase are contained in
      glycosomes. Cysteine protease is a metabolic enzyme, and its neutralization
      inhibits oxygen consumption and multiplication of the parasite. An important
      virulent factor in cryptobiosis is a secretory metalloprotease. The protective
      mechanism involves production of complement fixing antibodies, phagocytosis by
      macrophages, and cell-mediated cytotoxicity. Recovered fish are protected,
      probably for life as the immunity is non-sterile. Clinical signs of the disease
      include anaemia, anorexia, splenomegaly, general oedema and abdominal distension
      with ascites. The metabolism and swimming performance of infected fish are
      significantly reduced and the bioenergetic cost of the disease is very
      considerable. Fish are susceptible to hypoxia and their immune system is
      depressed during acute cryptobiosis. Severity of the disease and mortality rates
      vary significantly between species and stocks of salmon. Protective strategies
      include selective breeding of Cryptobia-resistant fish. This is innate resistance
      to infection and it is controlled by a dominant Mendelian locus. In these fish
      the parasite is lysed via the alternative pathway of complement activation. In
      Cryptobia-tolerant fish (infected with the pathogen but which do not suffer from
      disease) the metalloprotease secreted by the parasite is neutralized by alpha2
      macroglobulin. Hence, the production of a transgenic Cryptobia-tolerant salmon is
      an option. This strategy has the advantage in that human intervention (e.g.
      vaccination, chemotherapy) is not required once the transgenic fish is produced.
      Acquired immunity is another option; a single dose of the attenuated live vaccine
      protects fish for at least 2 years. The protective mechanism in vaccinated fish
      is similar to that in recovered fish. The trypanocidal drug, isometamidium
      chloride, is an effective therapeutic and prophylactic agent. It accumulates in
      the mitochondrium of the parasite and significantly disrupts aerobic respiration
      by causing lesions in the organelle. Efficacy of the drug is significantly
      increased after its conjugation to antibodies. This immuno-chemotherapeutic
      strategy has the advantage in that it will lower the drug dosage and hence side
      effects of chemotherapy. It will probably reduce the accumulation of the drug in
      fish, an important consideration in food fish.

PMID- 14710757
TI  - Tracing the route of Sphaerospora truttae from the entry locus to the target
      organ of the host, Salmo salar L., using an optimized and specific in situ
      hybridization technique.
AB  - Sphaerospora truttae is an important pathogen of Atlantic salmon parr in Scottish
      aquaculture. To trace the early development of S. truttae and to overcome the
      common problem of detecting low numbers of cryptic, early myxosporean stages, a
      DNA-based approach was applied in this study. Specific primers were designed for
      S. truttae from Atlantic salmon, based on 18S rDNA sequences, obtained from
      isolated myxosporean spores. These were 5' biotin-labelled and used in an
      optimized and rapid in situ hybridization (ISH) protocol, which provided a strong
      and specific signal of the parasite within host tissue sections and, at the same
      time, minimized structural damage to tissues due to processing. This methodology
      provided a reliable tool enabling the detection of S. truttae stages down to
      single cell level. Using ISH the epithelium of the gills was identified as the
      predominant entry locus of the parasite. By 3 days after infection S. truttae had
      penetrated the vascular epithelia and thereafter proliferated in the blood for at
      least 10 days before exiting the vascular system through capillary walls. From
      day 12 post-infection onwards, the kidney, as well as the spleen and the liver,
      were invaded. Numbers of S. truttae invading the kidney (37.3%) differed little
      from numbers found in the spleen (35.3%) and the liver (27.4%). The latter organs
      represented a dead end in the development of S. truttae as all stages in these
      organs degenerated and sporogony was found to take place exclusively inside the
      renal tubules. Early sporogonic stages were found from day 25 post-infection but
      mature spores only developed after at least 15 days of proliferation within the
      tubules.

PMID- 14710758
TI  - Establishment and characterization of two new cell lines derived from flounder,
      Paralichthys olivaceus (Temminck & Schlegel).
AB  - Two new cell cultures from flounder, Paralichthys olivaceus (Temminck &
      Schlegel), flounder fin (FFN) cells from fin tissue and flounder spleen (FSP)
      cells from spleen tissue, were established and characterized. The cells
      multiplied well in Eagle's minimum essential medium, supplemented with 10% foetal
      bovine serum, and have been subcultured more than 100 times, becoming continuous
      cell lines. Modal diploid chromosome number of FFN and FSP cells was 64 and 62,
      respectively. Polymerase chain reaction products were obtained from FFN and FSP
      cells with primer sets ofmicrosatellite markers of flounder. Optimal growth
      temperature was 20 degrees C and consisted of epithelioid cells. FFN and FSP
      cells showed cytopathic effects after inoculation of infectious pancreatic
      necrosis virus, marine birnavirus, chum salmon virus, infectious haematopoietic
      necrosis virus, spring viraemia of carp virus and hirame rhabdovirus. Thus these
      new cell lines may be useful for studying a wide range of fish viruses.

PMID- 14710759
TI  - A hyperparasitic microsporidian infecting the salmon louse, Lepeophtheirus
      salmonis: an rDNA-based molecular phylogenetic study.
AB  - The sea louse, Lepeophtheirus salmonis, is an obligate ectoparasitic copepod that
      lives on the external surface of salmonid fish. It is the most common
      ectoparasite of marine cage-reared salmonids, causing major economic loss to the
      aquaculture industry. During a sea louse monitoring programme, samples of L.
      salmonis were found to harbour an unreported microsporidian parasite. The
      microsporidian was observed in pre-adult and adult stages of both male and female
      copepods, with a prevalence of up to 5%. Unfixed spores were slightly pyriform in
      shape measuring 2.34 microm by 1.83 microm (+/- 0.01 microm) and were not
      observed to be enclosed by a sporophorous vesicle. The microsporidian infection
      was observed in all areas of the copepods' body, xenoma-like cysts forming
      directly under the cuticle in the epidermal tissue layer. In the present study,
      rDNA (530f-580r) sequence data gathered from the unidentified microsporidian
      parasite isolated from infected sea lice were compared with equivalents available
      in the databases in an attempt to identify its systematic position. The
      microsporidian was found to group within the phylogenetic clade containing the
      family Enterocytozoonidae, being most similar to members of the intranuclear
      genus Nucleospora. This is the first report of a hyperparasitic microsporidian
      infecting a caligid copepod.

PMID- 14710760
TI  - A novel serotype of Flavobacterium psychrophilum detected using antiserum against
      an isolate from amago, Oncorhynchus masou rhodurus Jordan & Gilbert, in Japan.

PMID- 14710761
TI  - Deuteromycotic fungi infecting barramundi cod, Cromileptes altivelis
      (Valenciennes), from Australia.

PMID- 14710762
TI  - Goitre in large and small spotted dogfish, Scyliorhinus stellaris (L.) and
      Scyliorhinus canicula (L.).

PMID- 14710763
TI  - First isolation of sleeping disease virus from rainbow trout, Oncorhynchus mykiss
      (Walbaum), in the United Kingdom.

PMID- 14710764
TI  - Periodontal ultrasonography.
AB  - OBJECTIVES: The aim of this study was to investigate high-frequency ultrasound
      imaging for periodontal assessment. MATERIAL AND METHODS: A newly developed
      ultrasonic scanner with a frequency of 20 MHz was used. Pig jaws were selected as
      the experimental model. Three teeth per jaw were imaged with the scanner and
      duplicate measurements were made of the distance from a fixed landmark on the
      teeth to the alveolar bone crest. These measurements were compared to
      transgingival and direct measurements of the same teeth following reflection of
      the soft tissues. One further jaw was used for histological comparison with the
      ultrasound image. RESULTS: Using ultrasonography, it was possible to image the
      main periodontal structures. The ultrasound measurements showed better
      repeatability than either of the other two methods (repeatability coefficient:
      0.44 mm for ultrasound, 0.93 mm for transgingival probing and 0.6 mm for direct
      measurements). Also, ultrasound was in better agreement with direct, open probing
      measurements (0.004 +/- 0.58 mm) than transgingival probing with direct
      measurements (0 +/- 0.7 mm). CONCLUSIONS: Ultrasonography provides a highly
      accurate and repeatable technique for periodontal assessment in this model.

PMID- 14710765
TI  - Effect of enamel matrix proteins (Emdogain') on healing after re-implantation of
      "periodontally compromised" roots. An experimental study in the dog.
AB  - OBJECTIVE: The present experiment was performed to assess whether Emdogain
      applied on the root surface of extracted teeth or teeth previously exposed to
      root planning can protect the tooth from ankylosis following re-implantation.
      MATERIAL AND METHODS: The experiment included two groups of dogs, including five
      animals each. The root canals of all mandibular third premolars (3 P 3) were
      reamed and filled with gutta-percha. A crestal incision was placed from the area
      of the second to the fourth premolar. Buccal and lingual full thickness flaps
      were elevated. With the use of a fissure bur, the crown and furcation area of 3 P
      3 were severed in an apico-coronal cut. The distal and mesial tooth segments were
      luxated with an elevator and extracted with forceps. Group A: The mesial and
      distal segments of 3 P 3 were air dried on a glass surface for 60 min. The roots
      from the right side were conditioned and exposed to Emdogain application. The
      roots from the left side received the same treatment with the exception of
      Emdogain application. The mesial and distal tooth segments were re-implanted and
      the crown portions were severed with a horizontal cut and removed. The buccal and
      lingual flaps were mobilized and sutured to obtain complete coverage of the
      submerged roots. Group B: A notch was prepared in each root, 4-5 mm apical of the
      cemento-enamel junction. The area of the root that was located coronal to the
      notch was scaled and planned. The roots in the right side of the mandible were
      treated with Emdogain, while the roots in the left side served as controls. After
      6 months of healing, the dogs were killed and blocks containing one root with
      surrounding tissues were harvested, and prepared for histological examination,
      which also included morphometric assessments. Thus, the proportions of the roots
      that exhibited signs of (i) replacement (ii) inflammatory and (iii) surface
      resorption were calculated. RESULTS AND CONCLUSION: It was demonstrated that
      healing of a re-implanted root that had been extracted and deprived of vital
      cementoblasts was characterized by processes that included root resorption,
      ankylosis and new attachment formation. It was also demonstrated that Emdogain
      treatment, i.e. conditioning with EDTA and placement of enamel matrix proteins on
      the detached root surface, failed to interfere with the healing process.

PMID- 14710766
TI  - Bilaminar techniques for the treatment of recession-type defects. A comparative
      clinical study.
AB  - OBJECTIVES: Complete root coverage is the primary objective to be accomplished
      when treating gingival recessions in patients with aesthetic demands.
      Furthermore, in order to satisfy patient demands fully, root coverage should be
      accomplished by soft tissue, the thickness and colour of which should not be
      distinguishable from those of adjacent soft tissue. The aim of the present split
      mouth study was to compare the treatment outcome of two surgical approaches of
      the bilaminar procedure in terms of (i) root coverage and (ii) aesthetic
      appearance of the surgically treated sites. MATERIAL AND METHODS: Fifteen young
      systemically and periodontally healthy subjects with two recession-type defects
      of similar depth affecting contralateral teeth in the aesthetic zone of the
      maxilla were enrolled in the study. All recessions fall into Miller class I or
      II. Randomization for test and control treatment was performed by coin toss
      immediately prior to surgery. All defects were treated with a bilaminar surgical
      technique: differences between test and control sites resided in the size,
      thickness and positioning of the connective tissue graft. The clinical re
      evaluation was made 1 year after surgery. RESULTS: The two bilaminar techniques
      resulted in a high percentage of root coverage (97.3% in the test and 94.7% in
      the control group) and complete root coverage (gingival margin at the cemento
      enamel junction (CEJ)) (86.7% in the test and 80% in the control teeth), with no
      statistically significant difference between them. Conversely, better aesthetic
      outcome and post-operative course were indicated by the patients for test
      compared to control sites. CONCLUSIONS: The proposed modification of the
      bilaminar technique improved the aesthetic outcome. The reduced size and minimal
      thickness of connective tissue graft, together with its positioning apical to the
      CEJ, facilitated graft coverage by means of the coronally advanced flap.

PMID- 14710767
TI  - Role of smoking and HbA1c level in periodontitis among insulin-dependent diabetic
      patients.
AB  - OBJECTIVES: The aim was to analyse the role of smoking and HbA1c level in
      attachment loss (AL) and probing depths (PDs) among insulin-dependent diabetic
      patients. MATERIAL AND-METHODS: The study subjects were selected from a group of
      149 insulin-dependent diabetic patients and included 64 patients (39 men and 25
      women) aged 30 years or older. Data were obtained from patient records and by
      clinical examination. The outcome variables were the number of sites with AL and
      PDs of 5-9 mm. Relative risks (RRs) with 95% confidence intervals (CIs) were
      estimated using Poisson regression models. RR was adjusted for the number of
      teeth, dental calculus and age. RESULTS: RR for AL among the smokers was 4.15
      (95% CI: 2.30-7.63) and that for PD among the smokers was 7.96 (95% CI: 4.91
      13.19). HbA1c was not related to AL or PD. Among smokers with HbA1c > 8.5, RR for
      AL was 12.34 (95% CI: 4.14-39.35), but RR was not elevated for PD. CONCLUSIONS:
      It can be concluded that the poor metabolic control together with smoking is
      extremely detrimental for AL.

PMID- 14710768
TI  - Salivary cystatin activity and cystatin C in experimental gingivitis in non
      smokers.
AB  - BACKGROUND: Subjects with natural gingivitis and periodontitis have elevated
      levels of salivary cystatins compared to periodontally healthy individuals.
      Experimental gingivitis studies, however, have yielded conflicting results. AIM:
      The present study investigated whether experimentally induced gingivitis is
      associated with changes in salivary cystatin levels. MATERIAL & METHODS: Plaque
      scores, bleeding indexes and whole saliva samples of 35 non-smoking young adults
      were collected at the start and at the end of an experimental gingivitis trial,
      and 3 weeks after resuming oral hygiene. The saliva samples were assayed for
      protein concentrations, cystatin activity and cystatin C concentration. RESULTS:
      During experimental gingivitis, plaque and bleeding scores increased
      significantly in all subjects and subsequently decreased significantly after
      reinstalment of oral hygiene procedures. No significant changes were observed for
      the protein concentration, cystatin activity and cystatin C concentration. No
      significant relation could be established between these salivary parameters and
      bleeding on marginal probing. CONCLUSION: The present study confirms earlier
      results from Lie et al. (2001) that no significant changes occur in salivary
      cystatin activity and cystatin C concentration during and after experimental
      gingivitis.

PMID- 14710769
TI  - Clinical course of chronic periodontitis. I. Role of gingivitis.
AB  - OBJECTIVES: The purpose of this study was to determine the influence of long
      standing gingival inflammation on periodontal attachment loss. On the basis of
      repeated examinations, the present report describes the influence of gingival
      inflammation on the initiation of periodontitis from 16 to 59 years of age.
      MATERIAL AND METHODS: The data originated from a 26-year longitudinal study of
      Norwegian males, who practiced daily oral home care and received state-of-the-art
      dental care. The initial examination included 565 individuals. Subsequent
      examinations took place in 1971, 1973, 1975, 1981, 1988 and 1995. Thus, the study
      covers the age range of 16-59 years. All tooth sites were divided into four
      categories according to their history of gingival inflammation over the entire
      observation period: sites always scoring GI = 0, GI = 1 and GI = 2 sites (GI =
      gingival index). Sites disclosing various GI scores at different observation
      periods were not considered. RESULTS: The mean cumulative attachment loss for non
      inflamed (GI = 0) sites in individuals approaching 60 years of age was 1.94 mm.
      Sites always scoring GI = 1 yielded 2.42 mm, and sites that always scored GI = 2
      exhibited 3.31 mm of periodontal attachment loss. At interproximal sites of all
      three groups where gingival trauma was assumed to be minimal or non-existent,
      only very few sites expressed attachment loss due to gingival recession (2-4%).
      At interproximal sites always scoring GI = 0, 20% loss of attachment was in the
      form of pocket formation by 59 years of age. The GI = 1 and the GI = 2 cohorts
      exhibited attachment loss with pocket formation in 28% and 54%, respectively.
      CONCLUSION: This study has shown that, as men approach 60 years of age, gingival
      sites that throughout the 26 years of observation bled on probing had
      approximately 70% more attachment loss than sites that were consistently non
      inflamed (GI = 0). Before 40 years of age, there was a slight increase in
      periodontal attachment loss due to pocket formation, but after this, the
      frequency increased significantly. Loss of attachment due to gingival recession
      was very small in all three groups. The fact that sites with non-inflamed gingiva
      also exhibited some loss of attachment and pocket formation may be explained by
      fluctuation in the variations of tissue status during long observation intervals
      combined with the presence of subclinical inflammation.

PMID- 14710770
TI  - Clinical course of chronic periodontitis. II. Incidence, characteristics and time
      of occurrence of the initial periodontal lesion.
AB  - AIM: The purpose of this study was to assess the initiation and progression of
      periodontal disease during adult life. MATERIALS AND METHODS: In a 26-year
      longitudinal investigation of the initiation and progression of chronic
      periodontitis that started in 1969 and included 565 men of Norwegian middle
      class, 223 who had participated in some, but not all, intermediate examinations
      presented at the last survey in 1995. Fifty-four individuals were available for
      examination in all seven surveys. RESULTS: Covering the age range from 16 to 60
      years, the study showed that at 16 years of age, 5% of the participants had
      initial loss of periodontal attachment (ILA > or = 2 mm) at one or more sites.
      Both the subject incidence and the site incidence increased with time, and by 32
      years of age, all individuals had one or more sites with loss of attachment. As
      age progressed, new lesions affected sites, so that as these men approached 60
      years of age approximately 50% of all available sites had ILA. An assessment of
      the intraoral distribution of the first periodontal lesion showed that,
      regardless of age, molars and bicuspids were most often affected. At and before
      the age of 40 years, the majority of ILA was found in buccal surfaces in the form
      of gingival recession. By 50 years, however, a greater proportion of sites
      presented with attachment loss attributed to pocket formation or a combination of
      pocket formation and gingival recession. As individuals neared 60 years of age,
      approximately half of the interproximal areas in posterior teeth had these
      lesions. CONCLUSION: This investigation has shown that, in a well-maintained
      population who practises oral home care and has regular check-ups, the incidence
      of incipient periodontal destruction increases with age, the highest rate occurs
      between 50 and 60 years, and gingival recession is the predominant lesion before
      40 years, while periodontal pocketing is the principal mode of destruction
      between 50 and 60 years of age.

PMID- 14710771
TI  - Clinical course of chronic periodontitis. III. Patterns, variations and risks of
      attachment loss.
AB  - AIM: The purpose of this study was to assess the rate of attachment loss during
      various stages of adult life in a well-maintained middle-class population.
      MATERIAL AND METHODS: The data originated from a 26-year longitudinal study of
      Norwegian males who had received regular and adequate dental care and practised
      daily oral home care. The initial examination in 1969 included 565 individuals
      aged between 16 and 34 years. Subsequent examinations took place in 1971, 1973,
      1975, 1981, 1988 and 1995. Thus, the study covers the age range of 16-59 years.
      The rate of the annual attachment loss was calculated as the difference between
      the individual mean attachment loss between two examinations divided by the years
      between examinations. The mean annualized relative risk of attachment loss was
      calculated as the frequency distribution of sites with initial periodontal
      attachment loss (loss of attachment at the first time of occurrence > or = 2 mm)
      and healthy sites (loss of attachment always < 2 mm). For comparison of
      significant changes in annual attachment loss rates between the age groups and
      mean annualized relative risks of attachment loss as they proceeded through adult
      life, the Wilcoxon Mann-Whitney U-test was used. RESULTS: The mean overall
      individual attachment loss during 44 years (between 16 and 59 years) totaled 2.44
      mm (range 0.14-2.44 mm), averaging an annual mean rate of 0.05 mm/year. The
      highest annual rate of attachment loss occurred before 35 years of age (0.08-0.1
      mm/year), after which the mean annual rate decreased to about 0.04-0.06 mm/year
      for the next three decades of life leading to 60 years. The mean annualized
      relative risk of initial attachment loss increased significantly from adolescence
      (1.2%) to the maximum at 30-34 years of age (6.9%). After the age of 34 years,
      the risk of initial attachment loss decreased again, but after the age of 40
      years, another continuous increase was observed. CONCLUSIONS: Over a 26-year
      period, 25% of the subjects went through adult life with healthy and stable
      periodontal conditions. The remaining 75% developed slight to moderately
      progressing periodontal disease with progression rates varying between 0.02 and
      0.1 mm/year with a cumulative mean of loss of attachment of 2.44 mm as they
      approached 60 years of age. The annual mean rate and the mean annualized risk of
      initial attachment loss were highest between 16 and 34 years of age. Only 20% of
      the sites continued to lose further attachment during the remainder of the
      observation period, and less than 1% of the sites showed substantial loss of
      attachment (> 4 mm).

PMID- 14710772
TI  - Effect of various chlorhexidine regimens on salivary bacteria and de novo plaque
      formation.
AB  - AIM: The aim of the present experiment was to study the effect of different
      chlorhexidine regimens on the number of bacteria in saliva, and on de novo plaque
      formation. MATERIAL AND METHODS: Ten subjects with gingivitis, but no signs of
      destructive periodontitis, were recruited. Following a screening examination, the
      volunteers were given oral hygiene instruction, meticulous scaling and
      professional mechanical tooth cleaning (PTC). The PTC was repeated once every 3
      days during a 2-week period to establish healthy gingival conditions. The study
      was designed as a double-blind cross-over clinical trial including three phases.
      Each experimental phase comprised one preparatory period of 7 days and one plaque
      accumulation period (no oral hygiene measures) of 4 days. During all preparatory
      periods, the volunteers (i) performed mechanical tooth cleaning using a
      toothbrush and dentifrice and (ii) were, in addition, given two sessions of PTC.
      The final PTC was delivered after bacterial sampling had been made on Day 0.
      Preparatory period A: the participants continued the self-performed plaque
      control regimen that employed only mechanical means. Preparatory period B: the
      participants were in addition instructed to rinse and gargle, twice daily, with a
      0.2% chlorhexidine mouthrinse. Preparatory period C: in addition to the above,
      the participants were instructed to brush the dorsum of the tongue for 60 s,
      twice daily, with a 1.0% chlorhexidine gel. Following each plaque accumulation
      period, there was a 10-day washout interval. The presence and amount of dental
      plaque (QHI) was scored after 1, 2 and 4 days of no oral hygiene. Samples of
      saliva were obtained on Day 0 and after 1 and 2 days. The samples were placed on
      Brucella agar plates and incubated (anaerobically) for 5 days. The total number
      of colony-forming units was determined and used to estimate the density of
      bacteria in saliva. RESULTS: In period A, the mean QHI increased from 1.0 (Day 1)
      to 1.4 (Day 2) and 2.1 (Day 4). The corresponding scores for periods B and C were
      0.5, 0.8, 1.6 and 0.3, 0.8, 1.2, respectively. At all re-examination intervals
      more plaque formed during period A than during periods B and C. Further, during
      period C, less plaque formed than that during period B. Saliva samples from Day 0
      in period A contained a larger number of TVC than the baseline samples in periods
      B and C. There was no significant difference in TVC among the groups on Day 2.
      CONCLUSION: The daily use of chlorhexidine as an adjunct to mechanical tooth
      cleaning markedly reduced the number of microorganisms that could be detected in
      saliva. The number of salivary bacteria may have influenced the amount of plaque
      that formed during an early phase of no oral hygiene.

PMID- 14710773
TI  - Isolated gingival metastasis from hepatocellular carcinoma mimicking a pyogenic
      granuloma.
AB  - BACKGROUND: Oral metastatic tumours are uncommon and account for approximately 1%
      of malignant oral neoplasms. RESULTS: If the cases where the oral location is in
      the jawbone, with secondary invasion to the oral soft tissue, are excluded, only
      10 cases of gingival metastasis from hepatocellular carcinoma (HCC) have been
      previously reported in the literature. The clinicopathologic features of an HCC
      with gingival metastasis are reported. Six months after the multicentric HCC and
      alcoholic cirrhosis was diagnosed, a 65-year-old male patient presented a rapidly
      growing, lobulated and reddish exophytic lesion that was located in the gum in
      the incisal region of the upper jaw. The lesion was excised, and the final
      diagnosis of gingival metastasis of the HCC was established. Diagnostic
      investigations did not show any evidence of other metastatic lesions. This
      article describes a case with solitary metastasis from HCC in the gingiva, an
      event that, to our knowledge, has not been previously published. CONCLUSIONS: The
      clinical appearance of isolated gingival metastasis from HCC in the present case
      mimicked a pyogenic granuloma.

PMID- 14710774
TI  - Cow's milk antibodies in patients with newly diagnosed type 1 diabetes: primary
      or secondary?

PMID- 14710775
TI  - Duration of breast feeding and bovine serum albumin antibody levels in type 1
      diabetes: a case-control study.
AB  - OBJECTIVE: To compare the levels of bovine serum albumin (BSA) antibodies and
      their relationship with duration of breast feeding, age of exposure to cow's
      milk, and human leukocyte antigen (HLA-DQ) genotype in children with and without
      type 1 diabetes. METHODS: Serum samples from 143 (0.3-14.7 yr) newly diagnosed
      children with type 1 diabetes and 107 unrelated control children (0.8-13.5 yr)
      were evaluated for BSA antibodies. Duration of breast feeding and exposure to
      cow's milk were recorded on questionnaires. HLA-DQ typing was determined by
      polymerase chain reaction. RESULTS: One hundred percent of the diabetic children
      were positive for BSA antibodies compared to 1.9% for healthy controls (p <
      0.001). Diabetic children also had higher levels of immunoglobulin G antibodies
      than unrelated controls (55.1 vs. 17.8 ng/mL, p < 0.0001). Duration of breast
      feeding (5.4 vs. 7.6 months, p < 0.02), but not age of exposure to cow's milk
      (8.3 vs. 9.2 months, p = 0.11), differed between cases and controls. There was no
      difference in antibody titer by duration of breast feeding or age of exposure to
      cow's milk in the cases or controls. CONCLUSION: Higher levels of antibodies to
      BSA were found in children recently diagnosed with type 1 diabetes compared to
      the controls, particularly those with high or moderate HLA-DQ genotypes. The BSA
      profile, however, does not seem to depend on duration of breast feeding or age of
      exposure to cow's milk in this population.

PMID- 14710776
TI  - Change in glycemic control predicts change in weight in adolescent boys with type
      1 diabetes.
AB  - OBJECTIVE: To characterize the intraindividual relationships between changes in
      weight, glycosylated hemoglobin (HbA1c) levels, and reported total daily insulin
      dose between clinic visits in adolescent boys with type 1 diabetes (T1D).
      RESEARCH DESIGN AND METHODS: Intraindividual changes in HbA1c, anthropometric
      data, and reported total daily insulin dose between consecutive visits for 94
      adolescent boys with T1D were analyzed. RESULTS: Average quarterly weight gain
      was 2.8 kg during periods of improving, 1.5 kg during periods of minimal change,
      and 0.8 kg during periods of worsening glycemic control (improving vs. minimal
      change p < 0.001; minimal change vs. worsening p = 0.11; improving vs. worsening
      p < 0.001). Analyzing the quarterly weight velocity according to change in
      reported total daily dose of insulin, we found significantly greater weight gain
      during intervals when the family reported a decreasing insulin dose compared to
      intervals when the family reported no change in insulin dose (p = 0.003).
      Conversely, weight change during periods of reported increasing insulin dose was
      similar to that when the family reported that the boy's insulin dose did not
      change. CONCLUSIONS: Quarterly weight velocity was correlated with degree of
      change in glycemic control between visits in adolescent boys with T1D. When
      weight loss or inadequate weight gain and worsening glycemic control occur, the
      possibility of insulin omission must be explored. Reviewing the adolescent's
      growth data and then the division of responsibilities for diabetes management
      within the family, clinicians must reconcile discrepancies between weight
      velocity and a reportedly adequate dose of insulin.

PMID- 14710777
TI  - Self-efficacy and its interrelation with family environment and metabolic control
      in Turkish adolescents with type 1 diabetes.
AB  - OBJECTIVE: To explore the relationship between self-efficacy, family environment
      (cohesion and organization) and metabolic control. RESEARCH DESIGN AND METHODS: A
      total of 100 adolescents with diabetes were assessed on a single occasion.
      Eligibility criteria were an age range of 11-18 yr, diagnosis of type 1 diabetes
      of at least 1 yr duration, and ability to complete the questionnaire unaided.
      Adolescents completed self-efficacy and family environment questionnaires.
      Metabolic control was assessed by HbA1c. Statistical analysis was performed using
      Statistical Package for the Social Sciences (SPSS) Version 10.0. Independent
      paired t-tests and Pearson's correlation coefficient were used as test methods.
      RESULTS: Boys and girls were comparable on self-efficacy, and self-efficacy
      scores were quite satisfactory for both boys and girls. There was a significant
      positive correlation between self-efficacy and family cohesion in girls, but self
      efficacy was not related to the family environment (cohesion and organization)
      and metabolic control in the total sample. CONCLUSION: In the present study,
      there was no relationship between self-efficacy, family environment, and
      metabolic control in the total sample, but in girls, self-efficacy and family
      cohesion was positively correlated.

PMID- 14710778
TI  - Prevention of type 2 diabetes in youth: etiology, promising interventions and
      recommendations.

PMID- 14710779
TI  - Transplantation immunology 2003: simplified approach.
AB  - Transplantation has been performed clinically for four decades and has become the
      standard of care for end-stage organ failure. Understanding of the immunobiology
      of transplantation has made tremendous advances, but knowledge still lags behind
      the clinical use. As a result, nonspecific immunosuppression remains the standard
      therapy. This article presents an overview of current knowledge of the
      immunobiology of solid organ transplantation, with emphasis on T-cell activation
      (antigen presentation, CoS) and cellular allograft (transplantation) immunity.
      The molecular events of T-cell activation, with some emphasis on the sites of
      action of modern immunosuppression, are reviewed. A simplified approach to
      understanding the immunobiology and strategy of maintenance immunosuppression is
      discussed. Key early and late steps in T-cell activation and the sites of action
      of immunosuppressive agents are reviewed. The required cellular interactions for
      the alloresponse and the targets of biologic agents used in transplants are
      reviewed. Special considerations for the immunology in neonates, infants, and
      children as recipients are provided. Understanding the immunobiology of
      transplantation is key to making decisions about children with transplants,
      developing better protocols, and creating tolerance in the future.

PMID- 14710780
TI  - Tolerance: is it achievable in pediatric solid organ transplantation?
AB  - Significant advances have been made in the understanding of allograft rejection.
      There is growing awareness that allograft acceptance, or tolerance, is also an
      active process rather than a passive absence of rejection. Mechanistic awareness
      of this process has spawned many preclinical strategies for the prevention of
      allograft rejection without the need for chronic immunosuppression. These
      therapies are currently entering clinical trials. This article reviews the
      prevailing therapies that hold promise for future clinical application. In
      particular, their application in children is discussed, as are biologic aspects
      of childhood immunity that may play a role in the success or failure of these
      strategies.

PMID- 14710782
TI  - Current status of kidney transplant: update 2003.
AB  - Pediatric transplantation has seen remarkable advances over the past two decades
      with reduced morbidity and mortality, reduced rejection rates, and improved long
      term patient and allograft survival. Infants currently have short-term patient
      and allograft survival rates better than any other age group; short-term
      allograft survival rates in CD recipients are equal to those in LD recipients.
      With decreased rejection, long-term allograft survival is improving dramatically.
      Transplantation allows for much reduced risks and improved metabolic status,
      growth and development, and more normal social interactions. The future of
      transplantation continues to be exciting, with opportunities for reduced
      immunosuppressive medications and their side effects, and the elusive goal of
      transplantation tolerance seems within reach.

PMID- 14710781
TI  - Current immunosuppressive agents: efficacy, side effects, and utilization.
AB  - Advances in immunosuppressive therapy over the past decade have led to dramatic
      improvements in graft survival. With the development of new agents, the focus of
      the transplant community is to establish regimens that maintain excellent graft
      survival rates but with fewer toxicities including infection, nephrotoxicity,
      malignancy, and cosmetic effects. Examples include the use of steroid-free
      protocols and calcineurin avoidance regimens, which are currently being studied
      by NAPRTCS. The ultimate goal of transplant immunosuppressive therapy is the
      induction of tolerance. As we learn more about immune function from basic and
      clinical research, tolerance to allografts seems a more reachable goal.

PMID- 14710783
TI  - Current status of liver transplantation in children.
AB  - There are two critical issues on opposite ends of the timeline for patients who
      are eligible for liver transplantation. On the one hand, the crisis in the
      cadaveric organ supply makes surviving to transplant ever more risky. On the
      other hand, patients who receive successful transplants face the consequences of
      long-term immunosuppression and its potentially life-threatening complications.
      The donor shortage is forcing difficult decisions that affect all patients who
      await liver transplantation. It is important to scrutinize carefully the results
      of all policies that govern allocation and the ethics of the solutions we
      advocate to ensure that no patient subgroup is being at a disadvantage. Current
      immunosuppression practices are being challenged by an increasing understanding
      of the immunologic events triggered by the allograft and the goal to free
      patients from consequences of a lifetime of immunosuppression. Clinicians can
      expect, and perhaps require, that new immunosuppressive protocols will address
      how the planned intervention might be expected to advance the understanding of
      tolerance mechanisms. As knowledge increases, clinicians can anticipate
      innovative new immunosuppressive proposals. Calcineurin and steroid-free
      induction, the use of donor-derived bone marrow infusion, recipient pretreatment,
      costimulatory blockade, and new antibody induction approaches are all being
      proposed--often in combination--for clinical trials. Researchers face additional
      challenges in defining endpoints if the goal is not just the short-term reduction
      in rejection but the minimization, and eventual discontinuation, of
      immunosuppressive drugs while maintaining excellent long-term graft function. How
      much "failure" will be accepted and how will it be defined? How will clinicians
      interpret liver biopsies if they begin to accept that some lymphocytic
      infiltrates may be beneficial mediators of the ongoing immune activation
      necessary for the maintenance of tolerance? How will they adjust
      immunosuppression practices to the dynamic processes in the immune response that
      maintain tolerance? Remarkable short-term successes in providing transplants for
      thousands of children with liver failure have brought these challenges into sharp
      focus. Clinicians must seek to move the life-giving science of transplantation
      toward a new goal: providing long lifetimes of excellent graft function with
      minimal toxicity from immunosuppressive drugs and the hope of freedom from
      immunosuppression altogether. Pediatric liver recipients, whose grafts have
      inherent tolerogenic potential and for whom we can anticipate decades of life
      after transplant, may prove to be an ideal study population to further these
      goals.

PMID- 14710784
TI  - Current status of heart transplantation in children: update 2003.
AB  - Heart transplant is an effective therapy for children with end-stage heart
      disease. Success of this treatment depends on coordination and careful
      communication among the family, primary care physician, and transplant team.
      Primary care physicians play an essential role in the monitoring and management
      of the medical, nutritional, developmental, and psychosocial issues of pediatric
      heart transplant patients and their families (Box 3). Ongoing assessment of the
      child and parent's progress in adapting to transplant is crucial in order for
      appropriate referrals to occur. Relationships with the primary care team can
      improve medical outcomes for this complex group of patients and provide a
      framework for improved adherence to care.

PMID- 14710785
TI  - Current status of small bowel transplantation in children: update 2003.
AB  - This article reviews the current indications for intestinal transplantation and
      advances in immunosuppression and postoperative care, which help to improve the
      outcome results of intestinal transplantation. Major current controversies and
      future trends are discussed briefly.

PMID- 14710786
TI  - Immunization of children after solid organ transplantation.
AB  - The array of immunizations commonly used in childhood has risen in an attempt to
      prevent many of the potentially serious infections of infancy and childhood. In
      this article, the authors provide rational guidelines for vaccination of these
      children. The authors briefly review the susceptibilities caused by
      immunosuppression in these patients, discuss the problems with various
      immunizations, and make individual recommendations regarding the use of each
      vaccine. Most recommendations are based on inferences from populations that may
      not be directly comparable to the transplantation population (patients with HIV
      or cancer or patients who have undergone bone marrow transplant), from case
      reports, and from small series of patients. The best recommendations ultimately
      must await the results of controlled trials of immunization.

PMID- 14710787
TI  - Infectious complications in pediatric solid organ transplantation.
AB  - Transplantation has emerged as one of the remarkable achievements of the latter
      half of the twentieth century for treatment of many end-stage organ disorders.
      Survival in pediatric solid organ transplantation continues to improve as
      strategies for immunosuppression, prevention and treatment of infectious
      complications progress. This article presents the summaries of the common and
      opportunistic pathogens that cause infectious complications for the pediatric
      transplant recipient. In addition, an approach to the pediatric transplant
      patient who presents with specific symptoms suggestive of infection is provided.

PMID- 14710788
TI  - Posttransplantation lymphoproliferative disorders.
AB  - Over the last decade, much has been learned about the nature of PTLD. The pivotal
      role of EBV infection in most cases has been established, and the pathologic
      description of lesions has been simplified in the current classification. It
      seems likely that further understanding of the molecular pathology may lead to
      greater ability to define optimal treatment regimens and prognosis. Quantitative
      PCR techniques for EBV have enhanced the capability for early diagnosis of EBV
      infection and PTLD and have proved useful tools for monitoring response to
      therapy. In particular, this technique seems to help predict when reintroduction
      of immunosuppression should be instituted. Several exciting new therapies are on
      the horizon, including use of monoclonal antibodies against B-cell surface
      antigens and the development of cellular therapies, such as the use of EBV
      specific cytotoxic T-cell infusions. Such strategies offer the promise of
      controlling abnormal B-cell proliferation without the risk of allograft
      rejection, because the host alloresponse is not enhanced by these therapies. The
      role of chemotherapy and the optimal regimens required remain to be defined
      fully. Understanding of the cause, behavior, and optimal treatment for EBV
      negative PTLD remains limited, partly because of the rarity of these lesions.
      There is an increasing level of interest in PTLD among clinical and basic
      investigators and recognition of the need for multicenter trials to define
      optimal prevention and treatment strategies. A degree of optimism seems
      warranted.

PMID- 14710789
TI  - Neurodevelopmental outcome of solid organ transplantation in children.
AB  - The literature regarding organ transplantation has emphasized graft survival in
      the arena of organ transplantation for life-threatening disease. The concept of
      "if you can't get it to work .... replace it" has been successful in the adult
      transplant population and has found its way into the pediatric population. With
      the improvement in patient and graft survival rates and management of
      complications, the questions multiply concerning quality-of-life issues.
      Neurodevelopmental outcome is emerging as one of the focal points for parents,
      physicians, and education specialists as they request information regarding early
      intervention and therapies for this growing population of children from the
      successful era of organ transplantation.

PMID- 14710790
TI  - Psychosocial adaptation after solid organ transplantation in children.
AB  - The possibility of extending life with advanced medical procedures such as organ
      transplantation in childhood has made it possible to focus on patients' well
      being in a wider perspective. They still experience a high prevalence of medical
      and physical disabilities, which definitively have an impact on a child's
      psychosocial adjustment after transplantation. Many disabilities originate before
      transplantation, and much effort should be taken to diminish possible
      complications and ameliorate growth and neurodevelopment, which have an impact
      for later adjustment regardless of a successful transplantation. Well-being and
      QOL are not necessarily always correlated to the degree of physical disability.
      Different social, financial, and demographic factors also have an impact, as do
      children's and families' ability to cope with a chronic disorder. Nonadherence
      and noncompliance are a great problem, particularly in adolescents. They are the
      result and a possible cause of inferior psychosocial adjustment. Continuous
      multidisciplinary support, follow-up, and education are needed to cope with this
      problem. Validated and reliable health status measures in pediatric transplant
      recipients are scarce in the literature, and few assessments can be completed by
      the children themselves. A continuing effort must be made to improve psychosocial
      adjustment and QOL after transplantation to achieve the ultimate goal in
      medicine: the overall well-being of our patients.

PMID- 14710791
TI  - Gynecologic issues of the adolescent female solid organ transplant recipient.
AB  - Advances in the field of transplant medicine are providing adolescent recipients
      with continual improvements in health and quality of life. With expanding
      opportunities for normal social and sexual relationships, adolescents require
      careful attention to their gynecologic and reproductive health (Box 1). Medical
      considerations vary depending on the type of organ transplanted, underlying and
      comorbid conditions, and current medication use. Most adolescent girls achieve
      menarche, however, and irregular cycles should be evaluated and managed with the
      same considerations applied to healthy young women. The management of menstrual
      disorders frequently uses hormonal contraceptive methods. Many transplant
      recipients also are sexually active and require a contraceptive method to prevent
      a mistimed pregnancy. With careful attention to organ function, other medical
      problems, and concurrently prescribed medications, many transplant recipients can
      use safely the currently available methods of hormonal contraception.

PMID- 14710792
TI  - Pregnancy in female pediatric solid organ transplant recipients.
AB  - This article from the National Transplantation Pregnancy Registry (NTPR)
      describes the pregnancy outcomes of female transplant recipients who received a
      solid organ transplant when younger than 21 years old. The analysis includes
      kidney, liver, liver-kidney, heart, and lung recipients. No recipients in the
      registry received a pancreas-kidney or heart-lung transplant before age 21. To
      date, the NTPR has not received report of a pregnancy in a small bowel recipient.
      This article also reviews immunosuppressive medications with regard to pregnancy
      safety.

PMID- 14710793
TI  - Transitioning care of the pediatric recipient to adult caregivers.
AB  - The development of transitional care is one of the major challenges for the
      twenty-first century as the survival rates and medical outcomes for child and
      adolescent recipients of solid organ transplants continue to improve. Such
      developments must include pediatric and adult care providers and require training
      of professionals in both arenas. Transition is a process in which the transfer to
      adult care is only one event within that process. The key elements of transition
      for pediatric recipients are discussed, and the importance of a coordinated,
      structured, multidisciplinary approach involving the adolescents themselves is
      highlighted.

PMID- 14710794
TI  - Communicating with families of patients in an acute hospital with advanced
      cancer: problems and strategies identified by nurses.
AB  - After pain management, poor communication with health professionals creates the
      most distress for families of patients with cancer. Difficulties communicating
      with families also have been identified as potentially stressful for nurses. This
      is particularly the case for nurses working in acute care settings. However,
      little research has been undertaken to examine the specific problems and
      challenges confronting nurses who endeavor to communicate with families of
      patients with cancer in a hospital setting. The purpose of this study was to
      describe nurses' perceptions of communication issues, potential barriers, and
      strategies associated with nurse-family interactions in an acute cancer hospital
      setting. Focus groups were conducted with nurses from two cancer wards at an
      Australia hospital. Four distinct themes emerged. First, all nurses described
      communication difficulties they encountered when interacting with families.
      Second, team factors appeared to be a central determinant of the quality of nurse
      family communication. Third, nurses described difficulties associated with the
      delivery of bad news and treatment plans that are not clearly defined for the
      patient. Finally, the effects of poor communication on nurses were notably and
      vividly described. In this report, recommendations for clinical practice and
      subsequent research are offered.

PMID- 14710795
TI  - Communication needs, methods, and perceived voice quality head and neck surgery:
      a literature review.
AB  - Patients with head and neck cancer experience complex and frustrating
      communication problems after surgery, yet patient communication during the in
      hospital postoperative period has received relatively little attention in
      clinical and research literature. A computerized and hand search of the medical
      (MEDLINE, Cancerlit), psychological (health and psychosocial instruments), and
      nursing (CINAHL) literature (1968 to August, 2001) produced 10 published studies
      and 1 clinical case report specifically addressing the communication needs,
      methods, or perceived voice quality of patients with head and neck cancer during
      the postoperative period (3 days to 19 months). This review presents a summary
      and critique of research and related literature on in-hospital postoperative
      communication with adult patients who have head and neck cancer. Four major
      themes are addressed: 1) information needs, 2) communication methods and
      perceived voice quality, 3) adjustment and adaptation to communication
      impairment, and 4) quality-of-life perceptions related to communication and
      socialization. This review shows that the communication needs, communication
      methods, and perception of voice quality among patients with head and neck cancer
      have been ignored during the in-hospital period. Clinical issues and
      technological advancements in augmentative and alternative communication
      applicable to the in-hospital period are discussed, and research implications are
      presented.

PMID- 14710796
TI  - Having a parent with cancer: coping and quality of life of children during
      serious illness in the family.
AB  - Little research has addressed how a parent's cancer affects young children. The
      purpose of this study was to explore the well-being and coping of young children
      during a period of cancer illness in the family. An explorative design was
      chosen, and data were collected through qualitative in-depth interviews with
      children (ages, 7-12 years) and their parents. Data were analyzed and interpreted
      within a phenomenologic-hermeneutic frame of understanding. Four major themes
      emerged in the findings: illness ruling in the family, reactions over and under
      the surface, many efforts to manage the situation, and feeling good most of the
      time. This report discusses how children's reactions and their management of such
      a difficult life event affect their quality of life. By going "in and out" of the
      situation, both literally and emotionally, the children cope with the situation
      and maintain a balance in life. In general, the children reported "feeling good,"
      but they put a lot of effort into it, and their quality of life appeared to be
      fragile. Their well-being was especially vulnerable at the time of the diagnosis
      and when the illness situation changed.

PMID- 14710797
TI  - Effect of unrealistic optimism, perceived control over disease, and experience
      with female cancer on behavioral intentions of Israeli women to undergo screening
      tests.
AB  - Early detection of cancer can lower mortality rates. Detection tests are
      available for some cancers such as breast and cervical cancer. Unrealistic
      optimism can affect compliance with health recommendations. Factors such as past
      experience (personal or at workplace) and perceived control over the disease
      influence unrealistic optimism. The purpose of this study was to examine the
      influence of past experience and perceived control over disease on unrealistic
      optimism towards breast and cervical cancer, and to examine the effect of
      unrealistic optimism, perceived control over the disease, and past experience on
      intentions to undergo screening tests. The study design was quasi-experimental
      correlative. Past experience was measured among 3 groups of women living in Tel
      Aviv ranging in age from 21 to 60 years: oncology nurses (n = 50), obstetric
      nurses (n = 50), and laywomen (n = 50). These groups were presumed to differ from
      each other in the extent to which they were aware of cancer. In addition, the 2
      types of malignancy represented different levels of awareness. Questionnaires
      were used to measure the study variables. Experience had a strong impact on
      unrealistic optimism with both cancers. However, the cancers differed in the
      impact of unrealistic optimism on behavioral intentions. With breast cancer (the
      more frequent), there was only a main effect of unrealistic optimism. A 3-way
      interaction was found with cervical cancer. The results indicate that unrealistic
      optimism plays a role in predicting participation in early detection testing and
      should be considered as an influencing factor in health-promoting plans.

PMID- 14710798
TI  - Hereditary breast cancer considering Cowden syndrome: a case study.
AB  - Hereditary breast cancer and the BRCA1 and BRCA2 genes have received a great deal
      of publicity over the past few years. Patients and family members frequently ask
      if they can be tested to see whether they have the "breast cancer gene," assuming
      that all breast cancers can be linked to one chromosomal site. Although the BRCA1
      and BRCA2 genes are the most common sites for hereditary breast cancer mutations,
      there are other hereditary gene mutations associated with breast cancer. Nurses
      should be aware of the spectrum of hereditary cancer syndromes and their
      associated "red flags." Important skills for the oncology nurse interested in
      genetic health include careful assessment of benign and malignant disease
      histories, alertness to physical findings, performance of risk assessments, and
      ability to access genetic health resources. The following case study describes
      the assessment process for a less common genetic disorder known as Cowden
      syndrome, or multiple hamartoma syndrome, a hereditary cancer syndrome associated
      with early-onset breast cancer, thyroid cancer, goiters, enlarged head size, and
      a variety of skin findings.

PMID- 14710799
TI  - Challenges of recruitment and retention in multisite clinical research.
AB  - This article reviews recruitment and retention issues in a multisite, multistate
      (California, New York, Connecticut, Georgia, Alabama) 6-month prospective cross
      sectional study focused on quality of life among 230 women with lung cancer.
      Recruitment of women into clinical trials and their retention are important, yet
      understudied. To date, few articles have described the challenges associated with
      recruiting women with lung cancer to participate in clinical research. Data from
      this trial were used to investigate the most effective strategies for recruitment
      across sites, to identify the most common reasons for refusal and attrition, and
      to identify challenges and potential solutions to recruitment and retention
      issues associated with multisite clinical research studies. Strategies for
      recruitment included letters from physicians, posters, announcements in community
      support groups, and newspaper and radio advertisements. Three sites allowed the
      researchers to contact potential participants directly, whereas 2 sites required
      the potential participants to contact the researchers for further information.
      Enrollment included 63% of the women eligible for the study (n = 230). The most
      common reasons for refusal were health limitations (n = 60), lack of interest (n
      = 46), and inconvenience (n = 16). The most common reasons for attrition (24% of
      the sample) were death (n = 21) and severity of illness (n = 13). Challenges
      related to recruitment and retention varied by geographic location.

PMID- 14710800
TI  - Research priorities of Korean oncology nurses.
AB  - Systematic nursing research activities in South Korea began in the 1970s, but
      research into oncology did not begin until the mid-1980s. Although the number of
      Korean oncology nursing studies has increased steadily since then, no national
      agenda exists for future research in oncology nursing. This study involved a
      descriptive survey of oncology nursing research priorities among Korean oncology
      nurses. The analysis included 59 members of the Korean Oncology Nursing Society.
      The questionnaire used by the Oncology Nursing Society in a US survey was revised
      and translated into Korean. The questionnaire contained 108 items. In addition,
      respondents were asked to rank 5 items in order of research priority. The Korean
      Oncology Nursing Society members ranked prevention of cancer and cancer risk
      reduction as the top research priority, followed by pain management, quality of
      life, hospice and end-of-life care, and standards of care. These findings provide
      the basis for developing a Korean oncology nursing research agenda, and for
      determining the direction of oncology research funding.

PMID- 14710801
TI  - Assisted dying and end-of-life symptom management.
AB  - This qualitative study aimed to describe symptom management strategies oncology
      nurses have used in responding to and preventing requests of terminally ill
      patients with cancer for assisted dying (AD). The study involved secondary
      analysis of written stories from 36 nurses who agreed to describe their
      experiences with a request for assisted dying. Of the 36 nurses, 12 refused to
      support patient requests for AD and described their attempts to control the
      circumstances of dying by controlling symptoms. The remaining 24 nurses denied
      ever receiving requests for AD and described symptom management practices
      believed to prevent such requests. Data were analyzed using Denzin's process of
      interpretive interactionism. Two themes emerged from the participant's stories:
      alternative strategies for AD and prevention of requests for AD. The participants
      shared many examples of clinical interventions and other features of nursing
      responses to relieve or prevent suffering including physical, emotional, and
      spiritual care practices; comfort and medication management; and service as
      teacher-advocate. Both the nurses who had received requests for AD and those who
      had not used a variety of similar symptom management approaches to alleviate
      suffering. In doing so, these nurses upheld current standards of both their
      professional and specialty organizations.

PMID- 14710802
TI  - Onward in my journey: preparing nurses for a new age of cancer care.
AB  - Cancer nursing education in the United Kingdom currently is the subject of
      widespread debate. The imperative to improve cancer care is driven by
      professional and ethical obligations for clinical excellence and an aggressive
      political agenda seeking to demonstrate tangible improvements through centrally
      administered targets and benchmarks. Attempts to provide a holistic approach to
      care have engendered a range of alternative approaches underpinned by an
      appreciation of the "cancer journey." Despite the laudable intent of national
      policy initiatives aimed at improving the experience of cancer treatment, they
      have evidenced an emerging polarization in the practice arena. Nursing
      interventions, priorities, and goals are at risk of becoming confused by the
      competing paradigms of an outcome-driven strategy and a less focused humanistic
      philosophy of care. This dilemma presents significant problems in the planning of
      appropriate and effective education preparation for cancer nurses. This article
      aims to address the tensions produced by a dichotomy between the pragmatics of
      clinical practice and a professional quest for holism. It focuses on a specialist
      practitioner cancer nursing program, using case examples to illustrate
      innovations in teaching and learning. Embracing a postmodern perspective,
      reflection, and critical thinking, the discussion offers a challenge to
      diagnostic clinical language through the discursive structures of metaphor,
      narrative, and story.

PMID- 14710803
TI  - Mammograms and Pap smears for Australian deaf women.
AB  - This study aimed to assess baseline knowledge about mammograms and Pap smears
      among Australian Deaf women, to investigate their participation in breast and
      cervical cancer screening services, and to explore, where relevant, their
      perceptions about their access to breast and cervical screening services. An
      interview schedule was developed, and a convenience sample of 13 Deaf women was
      interviewed face-to-face by the first researcher with an accredited Auslan
      interpreter. The Deaf women's knowledge about mammograms and Pap smears often was
      incomplete. However, most of the eligible women had undergone a mammogram and had
      been rescreened within the recommended time frame. Although most had received a
      Pap smear, some were not attending as recommended by the Cancer Council of
      Australia. This exploration into the experiences of Deaf women can prompt all
      nurses to consider the needs of particular minorities and the barriers they may
      face to participate fully in health services.

PMID- 14710804
TI  - Feasibility of exercise during treatment for multiple myeloma.
AB  - Fatigue and insomnia are problems for patients with cancer. Research findings
      show that aerobic exercise decreases cancer-related fatigue. Because patients
      with cancer who have skeletal muscle wasting may not obtain maximum benefit from
      aerobic exercise training, exercise programs may need to include resistance
      training. Thus far, testing exercise as an intervention for fatigue has focused
      on patients with breast cancer and excluded patients with bone metastasis. There
      is a need to test the feasibility and effectiveness of exercise for patients with
      other types of cancer and with bone involvement. The effect of aerobic and
      strength resistance training on the sleep of patients with cancer has not been
      tested. A pilot/feasibility study with a randomized controlled design was
      conducted to investigate home-based exercise therapy for 24 patients receiving
      high-dose chemotherapy and autologous peripheral blood stem cell transplantation
      as treatment for multiple myeloma. None of the patients injured themselves.
      Because of the small sample size in the feasibility study, the effect of exercise
      on lean body weight was the only end point that obtained statistical
      significance. However, the results suggest that an individualized exercise
      program for patients receiving aggressive treatment for multiple myeloma is
      feasible and may be effective for decreasing fatigue and mood disturbance, and
      for improving sleep.

PMID- 14710805
TI  - Autonomous detection of aerosolized Bacillus anthracis and Yersinia pestis.
AB  - We have developed and tested a fully autonomous pathogen detection system (APDS)
      capable of continuously monitoring the environment for airborne biological threat
      agents. The system is designed to provide early warning to civilians in the event
      of a terrorist attack. The final APDS will be completely automated, offering
      aerosol sampling, in-line sample preparation fluidics, multiplexed detection and
      identification immunoassays, and orthogonal, multiplexed PCR (nucleic acid)
      amplification and detection. The system performance (current capabilities include
      aerosol collection, multiplexed immunoassays, sample archiving, data reporting,
      and alarming) was evaluated in a field test conducted in a Biosafety Level 3
      facility, where the system was challenged with, and detected, a series of
      aerosolized releases containing two live, virulent biological threat agents
      (Bacillus anthracis and Yersinia pestis). Results presented here represent the
      first autonomous, simultaneous measurement of these agents.

PMID- 14710806
TI  - Integrated hydrogenated amorphous Si photodiode detector for microfluidic
      bioanalytical devices.
AB  - Hydrogenated amorphous silicon (a-Si:H) PIN photodiodes have been developed and
      characterized as fluorescence detectors for microfluidic analysis devices. A
      discrete a-Si:H photodiode is first fabricated on a glass substrate and used to
      detect fluorescent dye standards using conventional confocal microscopy. In this
      format, the limit of detection for fluorescein flowing in a 50-microm deep
      channel is 680 pM (S/N = 3). A hybrid integrated detection system consisting of a
      half-ball lens, a ZnS/YF3 multilayer optical interference filter with a pinhole,
      and an annular a-Si:H photodiode is also developed that allows the laser
      excitation to pass up through the central aperture in the detector. Using this
      integrated detection device, the limit of detection for fluorescein is 17 nM, and
      DNA fragment sizing and chiral analysis of glutamic acid are successfully
      performed. The a-Si:H detector exhibits high sensitivity at the emission
      wavelengths of commonly used fluorescent dyes and is readily microfabricated and
      integrated at low cost making it ideal for portable microfluidic bioanalyzers and
      emerging large scale integrated microfluidic technologies.

PMID- 14710807
TI  - Low-attomole electrospray ionization MS and MS/MS analysis of protein tryptic
      digests using 20-microm-i.d. polystyrene-divinylbenzene monolithic capillary
      columns.
AB  - This work explores the use of 20-microm-i.d. polymeric polystyrene-divinylbenzene
      monolithic nanocapillary columns for the LC-ESI-MS analysis of tryptic digest
      peptide mixtures. In contrast to the packing of microparticles, capillary columns
      were prepared, without the need of high pressure, in fused-silica capillaries, by
      thermally induced in situ copolymerization of styrene and divinylbenzene. The
      polymerization conditions and mobile-phase composition were optimized for
      chromatographic performance leading to efficiencies over 100000 plates/m for
      peptide separations. High mass sensitivity (approximately 10 amol of peptides) in
      the MS and MS/MS modes using an ion trap MS was found, a factor of up to 20-fold
      improvement over 75-microm-i.d. nanocolumns. A wide linear dynamic range
      (approximately 4 orders of magnitude) was achieved, and good run-to-run and
      column-to-column reproducibility of isocratic and gradient elution separations
      were found. As samples, both model proteins and tissue extracts were employed.
      Gradient nano-LC-MS analysis of a proteolytic digest of a tissue extract,
      equivalent to a sample size of approximately 1000 cells injected, is presented.

PMID- 14710808
TI  - Chemical ionization mass spectrometer instrument for the measurement of
      tropospheric HO2 and RO2.
AB  - Laboratory characterizations of the peroxy radical chemical ionization mass
      spectrometer (PerCIMS) instrument have been performed. The instrument functions
      by drawing ambient air through a 50-microm-diameter orifice into an inlet held at
      low pressure. Peroxy radicals (HO2 and RO2) within this air are detected by
      amplified chemical conversion into a unique ion (HSO4-) via the chemistry
      initiated by the addition of NO and SO2 to the inlet. HSO4- ions are then
      quantified by a quadrupole filter mass spectrometer. PerCIMS provides
      measurements of the sum of peroxy radicals, HO2 + RO2 (HOxROx mode), or the HO2
      component only (HO2 mode), achieved through the control of concentration of NO
      and SO2 added to the instrument. The characterization and response of this
      instrument have been evaluated through modeling of inlet chemistry and laboratory
      experiments and have also been demonstrated through successful deployment during
      field campaigns. The performance of PerCIMS with respect to calibration pressure
      and relative humidity is reported, as are the sensitivities of the instrument to
      organic peroxy radicals with different hydrocarbon groups. These data show
      PerCIMS to be a practical field instrument for the fast and accurate evaluation
      of the concentration of peroxy radicals over a variety of atmospheric conditions.
      The estimated accuracy of the derived [HOxROx] concentrations is +/- 35% (at the
      95% confidence interval), while [HO2] measurements have accuracies of +/- 41% (at
      the 95% confidence interval). Typical precision of measurements well above the
      detection limit is 10%, and typical detection limits are 1 x 10(7) radicals cm(
      3) for 15-s averaging times.

PMID- 14710809
TI  - Dual-function microanalytical device by in situ photolithographic grafting of
      porous polymer monolith: integrating solid-phase extraction and enzymatic
      digestion for peptide mass mapping.
AB  - Microfluidic devices with a dual function containing both a solid-phase extractor
      and an enzymatic microreactor have been prepared, and their operation has been
      demonstrated. The devices were fabricated from a 25-mm-long porous poly(butyl
      methacrylate-co-ethylene dimethacrylate) monolith prepared within a 50-microm
      i.d. capillary. This capillary with a pulled 9-12-microm needle tip was used as a
      nanoelectrospray emitter coupling the device to a mass spectrometer.
      Photografting with irradiation through a mask was then used to selectively
      functionalize a 20-mm-long portion of the monolith, introducing reactive poly(2
      vinyl-4,4-dimethylazlactone) chains to enable the subsequent attachment of
      trypsin, thereby creating an enzymatic microreactor with high proteolytic
      activity. The other 5 mm of unmodified hydrophobic monolith served as micro solid
      phase extractor (microSPE). The dual-function devices were used in two different
      flow directions; concentration of myoglobin that was absorbed from its dilute
      solution, followed by elution and digestion or digestion, followed by
      concentration. Operations in both directions afforded equal sequence coverage.
      Different volumes of myoglobin solution ranging from 2 to 20 microL were loaded
      on the device. Very high sequence coverages of almost 80% were achieved for the
      highest loading. Despite the very short length of the extractor unit, the device
      operated in the digest-solid-phase extraction direction also enabled the
      separation of peaks that mostly contained undigested protein and peptides.

PMID- 14710810
TI  - Graphical method for analysis of ultrahigh-resolution broadband mass spectra of
      natural organic matter, the van Krevelen diagram.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is becoming an important tool
      in the study of natural organic matter (NOM) at the molecular level. Ultrahigh
      resolution ESI-MS analyses of NOM often produce very complicated spectra;
      therefore, visual presentation and structural interpretations of the spectra are
      difficult. To meet this analytical challenge, we herein propose and demonstrate
      an approach using the van Krevelen diagram. With this approach, complicated mass
      spectra can be visualized in a way that allows for (1) possible reaction pathways
      to be identified and presented, and (2) qualitative analyses on major classes of
      compounds that comprise ultrahigh-resolution spectra. The qualitative analyses
      are in a good agreement with results obtained from analyses by other analytical
      techniques. Additionally, the van Krevelen diagram can be expanded to a 3D plot
      by using peak intensities or relative intensities as the z-axis. The 3D van
      Krevelen diagram allows for an evaluation of the relative significance of
      structurally related compounds. The 3D plot can also be a useful tool for
      compositional differentiation among samples.

PMID- 14710811
TI  - A filtration-based protein microarray technique.
AB  - Protein microarrays are an emerging technology for studying protein expression
      profiling and protein functions. However, with the current design approaches, the
      overall performance of protein microarrays can be compromised by diffusion
      limited kinetics. We developed a new protein microarray platform that utilizes a
      filtration assay with protein microarrays printed on protein-permeable
      nitrocellulose filter membranes. Compared with protein microarrays assayed with
      the conventional incubation-shaking method, this new approach overcomes the
      diffusion limit. We demonstrated that this novel technique can improve the
      overall reaction kinetic rate by 10-fold, yield a dynamic range of 4 decades, and
      enhance the assay sensitivity and specificity. Further, using multistacking
      protein chips, at least 14 chips can be probed simultaneously, with 22400
      different reactions in a single assay. The advantages of large fluorescent dyes,
      such as phycobilisome and quantum dots, can be better exploited using the
      filtration assay. The potential clinical applications of the filtration-based
      protein microarrays were demonstrated by detecting carcinoembryonic antigen in
      human plasma samples.

PMID- 14710813
TI  - Small molecules as mathematical partitions.
AB  - Small molecules can be represented as modular structures: small numbers of
      unbreakable cells, of known elemental composition, joined together at cleavable
      seams. The cells are a mathematical partition of the molecular weight. A
      systematic process is described here for converting mass spectral data into these
      simple modular structures; a computer program was then developed and tested using
      this process. On the basis of this preliminary work, it appears that this
      partitioning approach may be practicable for many compounds. Examples
      illustrating some of the limitations encountered with this approach are also
      presented.

PMID- 14710812
TI  - A chemometric approach for brain tumor classification using magnetic resonance
      imaging and spectroscopy.
AB  - A new classification approach was developed to improve the noninvasive diagnosis
      of brain tumors. Within this approach, information is extracted from magnetic
      resonance imaging and spectroscopy data, from which the relative location and
      distribution of selected tumor classes in feature space can be calculated. This
      relative location and distribution is used to select the best information
      extraction procedure, to identify overlapping tumor classes, and to calculate
      probabilities of class membership. These probabilities are very important, since
      they provide information about the reliability of classification and might
      provide information about the heterogeneity of the tissue. Classification
      boundaries were calculated by setting thresholds for each investigated tumor
      class, which enabled the classification of new objects. Results on
      histopathologically determined tumors are excellent, demonstrated by spatial maps
      showing a high probability for the correctly identified tumor class and,
      moreover, low probabilities for other tumor classes.

PMID- 14710814
TI  - Spatial profiling with MALDI MS: distribution of neuropeptides within single
      neurons.
AB  - MALDI MS imaging and single-cell profiling are important new capabilities for
      mass spectrometry. The distribution of neuropeptides within a cell plays an
      important role in the functioning of the cells in a neuronal network. Protocols
      for subcellular MALDI MS are described that allow comparative peptide profiling
      of cell bodies and the neuronal processes (neurites) using single isolated
      neurons from the neuronal model Aplysia californica. The seawater surrounding the
      neurons is problematic for mass spectrometry and so must be removed in a manner
      that does not cause morphological changes or a redistribution of the
      neuropeptides. Several protocols have been investigated for subcellular spatial
      profiling, including the use of air-drying, replacement of the seawater with
      deionized water, and substitution of the cell matrix with fluorinert, mineral oil
      and glycerol, as well as paraformaldehyde fixation. Glycerol stabilization offers
      the best combination of preservation of cell morphology and prevention of
      neuropeptide redistribution. The profiles of the peptides in specific neuronal
      processes and the cell bodies demonstrate a variety of differences that appear to
      be cell-specific. These methods are suitable for smaller cells and subcellular MS
      imaging.

PMID- 14710815
TI  - Ultrafast microfluidic mixer and freeze-quenching device.
AB  - The freeze-quenching technique is extremely useful for trapping meta-stable
      intermediates populated during fast chemical or biochemical reactions. The
      application of this technique, however, is limited by the long mixing time of
      conventional solution mixers and the slow freezing time of cryogenic fluids. To
      overcome these problems, we have designed and tested a novel microfluidic silicon
      mixer equipped with a new freeze-quenching device, with which reactions can be
      followed down to 50 micros. In the microfluidic silicon mixer, seven 10-microm
      diameter vertical pillars are arranged perpendicular to the flow direction and in
      a staggered fashion in the 450-pL mixing chamber to enhance turbulent mixing. The
      mixed-solution jet, with a cross section of 10 microm x 100 microm, exits from
      the microfluidic silicon mixer with a linear flow velocity of 20 m/s. It
      instantaneously freezes on one of two rotating copper wheels maintained at 77 K
      and is subsequently ground into an ultrafine powder. The ultrafine frozen powder
      exhibits excellent spectral quality and high packing factor and can be readily
      transferred between spectroscopic observation cells. The microfluidic mixer was
      tested by the reaction between azide and myoglobin at pH 5.0. It was found that
      complete mixing was achieved within the mixing dead time of the mixer (20
      micros), and the first observable point for this coupled device was determined to
      be 50 micros, which is approximately 2 orders of magnitude faster than
      commercially available instruments.

PMID- 14710816
TI  - Quartz crystal microbalance sensor for organic vapor detection based on
      molecularly imprinted polymers.
AB  - Molecularly imprinted polymers on quartz crystal microbalances (QCM) are examined
      for their ability to detect vapors of small organic molecules with greater
      sensitivity and selectivity than the traditional amorphous polymer coatings.
      Hydroquinone and phenol serve as noncovalently bound templates that generate
      shape-selective cavities in a poly(acrylic) or poly(methacrylic) polymer matrix.
      The imprinted polymers are immobilized on the piezoelectric crystal surface via a
      precoated poly(isobutylene) layer. The behavior of the imprinted polymer films is
      characterized by the dynamic and steady-state response of the QCM frequency to
      pulses of organic vapors in dry air. The apparent partition coefficients are
      determined for imprinted and nonimprinted polymers prepared by two synthetic
      methods and for varying mole ratios of template to monomer. The hydroquinone
      imprinted polymers and, to a lesser extent, the phenol-imprinted polymers exhibit
      greater sensitivity and higher selectivity than the nonimprinted polymers toward
      organic vapors that are structurally related to the templates. These results
      indicate that molecularly imprinted polymers are promising for the development of
      selective piezoelectric sensors for organic vapor detection.

PMID- 14710817
TI  - Monocrystalline diamond paste-based electrodes and their applications for the
      determination of Fe(II) in vitamins.
AB  - A new class of electrochemical sensors, namely, electrodes based on diamond
      paste, was designed using monocrystalline diamond (natural diamond 1 microm and
      synthetic diamond, 50 microm (synthetic-1) and 1 microm (synthetic-2)) powder and
      paraffin oil. The characterization of the electrodes was performed using cyclic
      voltammetry and differential pulse voltammetry. Fe(II) was determined by
      differential pulse voltammetry (DPV) at 75 mV (vs Ag/AgCl) using all diamond
      paste-based electrodes. The linear concentration range was between 10(-8) and 10(
      4) mol/L for both the natural diamond and synthetic-2 with detection limits of
      10(-10) and 10(-9) mol/L, respectively, whereas the linear concentration range
      for synthetic-1 was between 10(-7) and 10(-3) mol/L with a detection limit of 10(
      8) mol/L Fe(II) was determined successfully from four types of pharmaceutical
      products. The recovery values of Fe(II) in the pharmaceutical products were
      higher than 98.00% with relative standard deviation values < 5%.

PMID- 14710818
TI  - Electrochemically deposited sol-gel-derived silicate films as a viable
      alternative in thin-film design.
AB  - Sol-gel-derived silicate films were electrochemically deposited on conducting
      surfaces from a sol consisting of tetramethoxysilane (TMOS). In this method, a
      sufficiently negative potential is applied to the electrode surface to reduce
      oxygen to hydroxyl ions, which serves as the catalyst for the hydrolysis and
      condensation of TMOS. The electrodeposition process was followed by the
      electrochemical quartz crystal microbalance and cyclic voltammetry. The
      electrodeposited films were characterized for their surface morphology, porosity,
      and film thickness using atomic force microscopy, electrochemical probe
      techniques, surface area and pore size analysis, and profilometry. The
      electrodeposited films were found to have a completely different surface
      structure and to be significantly rougher relative to spin-coated films. This is
      likely due in part to the separation of the gelation and evaporation stages of
      film formation. The electrodeposited films were found to be permeable to simple
      redox molecules, such as ruthenium(III) hexaammine and ferrocene methanol. Film
      thickness can be easily varied from < 75 nm to > 15 microm by varying the
      electrode potential from -600 mV to more than -1000 mV, respectively. The
      electrodeposition process was further applied for the electroencapsulation of
      redox molecules and organic dyes within the silicate network. Cyclic
      voltammograms for the gel-entrapped ferrocene methanol (FcCH2OH) and
      ruthenium(II) tris(bipyridine) (Ru(bpy)3(2+)) exhibited the characteristic redox
      behavior of the molecules. The electroencapsulation of organic dyes in their
      "native" form proved to be more difficult because these species typically contain
      reducible functionalities that change the structure of the dye.

PMID- 14710819
TI  - Fabrication of integrated microelectrodes for electrochemical detection on
      electrophoresis microchip by electroless deposition and micromolding in capillary
      technique.
AB  - A new method for the fabrication of an integrated microelectrode for
      electrochemical detection (ECD) on an electrophoresis microchip is described. The
      pattern of the microelectrode was directly made on the surface of a microscope
      slide through an electroless deposition procedure. The surface of the slide was
      first selectively coated with a thin layer of sodium silicate through a
      micromolding in capillary technique provided by a poly(dimethylsiloxane) (PDMS)
      microchannel; this left a rough patterned area for the anchoring of catalytic
      particles. A metal layer was deposited on the pattern guided by these catalytic
      particles and was used as the working electrode. Factors influencing the
      fabrication procedure were discussed. The whole chip was built by reversibly
      sealing the slide to another PDMS layer with electrophoresis microchannels at
      room temperature. This approach eliminates the need of clean room facilities and
      expensive apparatus such as for vacuum deposition or sputtering and makes it
      possible to produce patterned electrodes suitable for ECD on microchip under
      ordinary chemistry laboratory conditions. Also once the micropattern is ready, it
      allows the researchers to rebuild the electrode in a short period of time when an
      electrode failure occurs. Copper and gold microelectrodes were fabricated by this
      technique. Glucose, dopamine, and catechol as model analytes were tested.

PMID- 14710820
TI  - Carbon nanotube purification: preparation and characterization of carbon nanotube
      paste electrodes.
AB  - Paste electrodes have been constructed using single-wall carbon nanotubes mixed
      with mineral oil. The electrochemical behavior of such electrodes prepared with
      different percentages of carbon nanotubes has been compared with that of graphite
      paste electrodes and evaluated with respect to the electrochemistry of
      ferricyanide with cyclic voltammetry. Carbon nanotubes were purified by a
      treatment with concentrated nitric acid, then oxidized in air. In addition,
      electrochemical pretreatments were carried out to increase the selectivity of
      carbon nanotube electrodes. Performances of carbon nanotube paste and carbon
      paste electrodes were evaluated by studying such parameters as current peak,
      deltaEp, anodic and cathodic current ratio, and charge density toward several
      different electroactive molecules. Data interpretation based on the carbon
      nanotubes and carbon surface area is presented. Carbon nanotube paste and carbon
      paste electrodes were tested as H2O2 and NADH probes, and several analytical
      parameters were evaluated. The oxidative behavior of dopamine was examined at
      these electrodes. The two-electron oxidation of dopamine to dopaminequinone
      showed an excellent reversibility in cyclic voltammetry that was significantly
      better than that observed at carbon paste electrodes.

PMID- 14710821
TI  - Composite carbon paste biosensor for phenolic derivatives based on in situ
      electrogenerated polypyrrole binder.
AB  - Amperometric biosensors based on new composite carbon paste (CPE) electrodes have
      been designed for the determination of phenolic compounds. The composite CPEs
      were prepared by in situ generation of polypyrrole (PPy) within a paste
      containing the enzyme polyphenol oxidase (PPO). The best paste composition
      (enzyme/pyrrole monomer/carbon particles/Nujol) was determined for a model
      enzyme, glucose oxidase, according to the enzymatic activity of the resulting
      electrodes and to the enzyme leakage from the paste during storage in phosphate
      buffer. The in situ electrogenerated PPy enables improvement in enzyme
      immobilization within the paste since practically no enzyme was lost in solution
      after 72 h of immersion. Moreover, the enzyme activity remains particularly
      stable under storage since the biocomposite structure maintains 80% of its
      activity after 1-month storage. Following the optimization of the paste
      composition, PPO-based carbon paste biosensors were prepared and presented
      excellent analytical properties toward catechol detection with a sensitivity of
      4.7 A M(-1) cm(-2) and a response time lower than 20 s. The resulting biosensors
      were finally applied to the determination of epicatechin and ferulic acid as
      flavonol and polyphenol model, respectively.

PMID- 14710822
TI  - Reagentless amperometric immunosensors based on direct electrochemistry of
      horseradish peroxidase for determination of carcinoma antigen-125.
AB  - A novel strategy for immunoassay and the preparation of reagentless immunosensors
      was proposed. This strategy was based on the immobilization of antigen and the
      direct electrochemistry of horseradish peroxidase (HRP) that was labeled to an
      antibody. A reagentless immunosensor for carcinoma antigen-125 (CA 125)
      determination was developed. The immunosensor was prepared by immobilizing CA 125
      with titania sol-gel on a glassy carbon electrode by the vapor deposition method.
      The incubation of the immunosensor in phosphate buffer solution (PBS) including
      HRP-labeled CA 125 antibody led to the formation of a HRP-modified surface. The
      immobilized HRP displayed its direct electrochemistry with a rate constant of
      3.04 +/- 1.21 s(-1). With a competition mechanism, a differential pulse
      voltammetric determination method for CA 125 was established by the peak current
      decrease of the immobilized HRP. The current decrease resulted from the
      competitive binding of the CA 125 in sample solution and the immobilized CA 125
      to the limited amount of HRP-labeled CA 125 antibody. Under optimal conditions,
      the current decrease was proportional to CA 125 concentration ranging from 2 to
      14 units mL(-1) with a detection limit of 1.29 units mL(-1) at a current decrease
      by 10%. The CA 125 immunosensor showed good accuracy and acceptable precision and
      fabrication reproducibility with intraassay CVs of 8.7 and 5.5% at 8 and 14 units
      mL(-1) CA 125 concentrations, respectively, and interassay CV of 19.8% at 8 units
      mL(-1). The storage stability was acceptable in a pH 7.0 PBS at 4 degrees C for
      15 days. The proposed method provided a new promising platform for clinical
      immunoassay.

PMID- 14710823
TI  - Microchip capillary electrophoresis with an integrated indium tin oxide electrode
      based electrochemiluminescence detector.
AB  - This paper describes an indium tin oxide (ITO) electrode-based Ru(bpy)3(2+)
      electrochemiluminecence (ECL) detector for a microchip capillary electrophoresis
      (CE). The microchip CE-ECL system described in this article consists of a
      poly(dimethylsiloxane) (PDMS) layer containing separation and injection channels
      and an electrode plate with an ITO electrode fabricated by a photolithographic
      method. The PDMS layer was reversibly bound to the ITO electrode plate, which
      greatly simplified the alignment of the separation channel with the working
      electrode and enhanced the photon-capturing efficiency. In our study, the high
      separation electric field had no significant influence on the ECL detector, and
      decouplers for isolating the separation electric field were not needed in the
      microchip CE-ECL system. The ITO electrodes employed in the experiments displayed
      good durability and stability in the analytical procedures. Proline was selected
      to perform the microchip device with a limit of detection of 1.2 microM (S/N = 3)
      and a linear range from 5 to 600 microM.

PMID- 14710824
TI  - Mass spectrometry and tandem mass spectrometry of citrus limonoids.
AB  - Methods for atmospheric pressure chemical ionization tandem mass spectrometry
      (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass
      spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation
      patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and
      deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D
      glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17
      beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside
      (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D
      glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in
      low-energy collisionally activated dissociation (CAD). The four limonoid
      aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from
      citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively
      identified in the crude extract of grapefruit seeds by ESI mass spectrometry in
      both positive and negative ion analysis. Ammonium hydroxide or acetic acid was
      added to the mobile phase to facilitate ionization. During positive ion APCI
      analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct
      ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added
      to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc 
      H] and [M + HOAc]-) or a deprotonated molecular ion were produced during
      negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase
      modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of
      [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the
      mobile phase. After collisionally activated dissociation (CAD) of the limonoid
      aglycone molecular ions in negative ion APCI analysis, fragment ions indicated
      structural information of the precursor ions, showing the presence of methyl,
      carboxyl, and oxygenated ring structure. CAD of the adduct ion [M + H + NH3]+ of
      limonoid glucosides produced the aglycone moiety corresponding to each glucoside.
      The combination of mass spectrometry and tandem mass spectrometry provides a
      powerful technique for identification and characterization of citrus limonoids.

PMID- 14710825
TI  - Development of a poly(dimethylsiloxane) interface for on-line capillary column
      liquid chromatography-capillary electrophoresis coupled to sheathless
      electrospray ionization time-of-flight mass spectrometry.
AB  - An interface in elastomeric poly(dimethylsiloxane) (PDMS) for on-line orthogonal
      coupling of packed capillary liquid chromatography (LC) (i.d. = 0.2 mm) with
      capillary electrophoresis (CE) in combination with sheathless electrospray
      ionization (ESI) time-of-flight mass spectrometric (TOFMS) detection is
      presented. The new interface has a two-level design, which in combination with a
      continuous CE electrolyte flow through the interface provides integrity of the LC
      effluent and the CE separation until an injection is desired. The transparent and
      flexible PDMS material was found to have a number of advantages when combined
      with fused silica column technology, including ease to follow the process and
      ease to exchange columns. By combining conventional microscale systems of LC, CE,
      and ESI-MS, respectively, the time scales of the individual dimensions were
      harmonized for optimal peak capacity per unit time. The performance of the LC-CE
      TOFMS system was evaluated using peptides as model substances. A S/N of about 330
      was achieved for leucine-enkephaline from a 0.5 microL LC injection of 25
      microg/mL peptide standard.

PMID- 14710826
TI  - The effect of small cations on the positive electrospray responses of proteins at
      low pH.
AB  - Solutions consisting of protein and small molecule mixtures have been subjected
      to electrospray ionization to study the influence of small molecule/cation
      components at high concentrations on the electrospray responses of proteins.
      Emphasis was placed on solutions consisting of equal parts methanol and water and
      containing 1 vol % acetic acid. The results, therefore, are relevant to low pH
      solutions with significant organic content, a commonly used set of conditions in
      electrospray ionization mass spectrometry that tends to denature proteins. A
      variety of small cations/molecules were selected to sample a range of chemical
      characteristics. For example, sodium and cesium cations were studied to represent
      metal ions, tetrabutylammonium and tetramethylammonium cations were studied to
      represent quaternary ammonium compounds with different surface activities, and
      octadecylamine and glycine were studied to represent species that compete for
      protons but have different surface activities. A methodology for measuring
      relative ion suppression efficiencies was developed and applied for protein ions
      derived from bovine cytochrome c. The form of the small cation (i.e., metal ion,
      quaternary ammonium ion, or protonated molecule) did not appear to be a factor in
      determining the efficiency with which protein ion signals were suppressed. The
      extent to which ions are expected to concentrate on the surface, however, was the
      major factor in determining the ion suppression efficiency. Itwas found that the
      ion suppression efficiency of the most surface active species in this study was
      comparable to that of a protein on another protein after normalization by charge.
      These results are particularly relevant to the development of mixture analysis
      strategies based on ionization and tandem mass spectrometry applied to mixtures
      of whole proteins.

PMID- 14710827
TI  - Quantitative analysis with desorption/ionization on silicon mass spectrometry
      using electrospray deposition.
AB  - Desorption/ionization on silicon mass spectrometry (DIOS-MS) is demonstrated as a
      quantitative analytical tool when coupled to electrospray deposition (ESD). In
      this study, we illustrate the utility of DIOS-MS in the quantitative analysis of
      a peptide and two amino acids with deuterated and structural analogues used as
      internal standards. An important feature of this approach is the incorporation of
      ESD to improve sample homogeneity across the porous silicon surface. ESD allowed
      for a marked improvement in quantitative analysis due to its applicability to LC
      DIOS, and because of the absence of matrix, sample can be deposited at very low
      flow rates (150 nL/min). Experiments comparing the traditional dried droplet and
      ESD methods show that ESD samples exhibit significantly improved quantitation and
      much higher sample-to-sample reproducibility.

PMID- 14710828
TI  - Laser power dependence of mass spectral signatures from individual bacterial
      spores in bioaerosol mass spectrometry.
AB  - Bioaerosol mass spectrometry is being developed to analyze and identify
      biological aerosols in real time. Characteristic mass spectra from individual
      bacterial endospores of Bacillus subtilis var. niger were obtained in a bipolar
      aerosol time-of-flight mass spectrometer using a pulsed 266-nm laser for
      molecular desorption and ionization. Spectra from single spores collected at an
      average fluence of approximately 0.1 J/cm2 frequently contain prominent peaks
      attributed to arginine, dipicolinic acid, and glutamic acid, but the shot-to-shot
      (spore-to-spore) variability in the data may make it difficult to consistently
      distinguish closely related Bacillus species with an automated routine.
      Fortunately, a study of the laser power dependence of the mass spectra reveals
      clear trends and a finite number of "spectral types" that span most of the
      variability. This, we will show, indicates that a significant fraction of the
      variability must be attributed to fluence variations in the profile of the laser
      beam.

PMID- 14710829
TI  - Proton transfer reaction mass spectrometry, a tool for on-line monitoring of
      acrylamide formation in the headspace of maillard reaction systems and processed
      food.
AB  - The formation of acrylamide was measured in real time during thermal treatment
      (120-170 degrees C) of potato as well as in Maillard model systems composed of
      asparagine and reducing sugars, such as fructose and glucose. This was achieved
      by on-line monitoring of acrylamide released into the headspace of the samples
      using proton transfer reaction mass spectrometry (PTR-MS). Unambiguous
      identification of acrylamide by PTR-MS was accomplished by gas chromatography
      coupled simultaneously to electron-impact MS and PTR-MS. The PTR-MS ion signal at
      m/z 72 was shown to be exclusively due to protonated acrylamide obtained without
      fragmentation. In model Maillard systems, the formation of acrylamide from
      asparagine was favored with increasing temperature and preferably in the presence
      of fructose. Maximum signal intensities in the headspace were obtained after
      approximately 2 min at 170 degrees C, whereas 6-7 min was required at 150 degrees
      C. Similarly, the level of acrylamide released into the headspace during thermal
      treatment of potato was positively correlated to temperature.

PMID- 14710830
TI  - High-precision position-specific isotope analysis of 13C/12C in leucine and
      methionine analogues.
AB  - We report an automated method for high-precision position-specific isotope
      analysis (PSIA) of carbon in amino acid analogues. Carbon isotope ratios are
      measured for gas-phase pyrolysis fragments from multiple sources of 3
      methylthiopropylamine (3MTP) and isoamylamine (IAA), the decarboxylated analogues
      of methionine and leucine, using a home-built gas chromatography (GC)-pyrolysis
      GC preparation system coupled to a combustion-isotope ratio mass spectrometry
      system. Over a temperature range of 620-900 degrees C, the characteristic
      pyrolysis products for 3MTP were CH4, C2H6, HCN, and CH3CN and for IAA products
      were propylene, isobutylene, HCN, and CH3CN. Fragment origin was confirmed by 13C
      labeling, and fragments used for isotope analysis were generated from unique
      moieties with > 95% structural fidelity. Isotope ratios for the fragments were
      determined with an average precision of SD(delta13C) < 0.3% per thousand, and
      relative isotope ratios of fragments from different sources were determined with
      an average precision of SD(delta(delta)13C) < 0.5% per thousand. Delta(delta)13C
      values of fragments were invariant over a range of pyrolysis temperatures. The
      delta(delta)13C of complementary fragments in IAA was within 0.8% per thousand of
      the delta(delta)13C of the parent compounds, indicating that pyrolysis-induced
      isotopic fractionation is effectively taken into account with this calibration
      procedure. Using delta(delta)13C values of fragments, delta(delta)13C values were
      determined for all four carbon positions of 3MTP and for C1, C2, and the propyl
      moiety of IAA, either directly or indirectly by mass balance. Large variations in
      position-specific isotope ratios were observed in samples from different
      commercial sources. Most dramatically, two 3MTP sources differed by 16.30% per
      thousand at C1, 48.33% per thousand at C2, 0.37% per thousand at C3, and 5.36%
      per thousand at C(methyl). These PSIA techniques are suitable for studying subtle
      changes in intramolecular isotope ratios due to natural processes.

PMID- 14710831
TI  - Chip-based solid-phase extraction pretreatment for direct electrospray mass
      spectrometry analysis using an array of monolithic columns in a polymeric
      substrate.
AB  - An array of eight porous monolithic columns, prepared in a Zeonor polymeric chip
      by UV-initiated polymerization of butyl methacrylate and ethylene dimethacrylate,
      was tested for solid-phase extraction (SPE) cleanup of biological samples prior
      to directly coupled electrospray mass spectrometry (ESI-MS). The chip, fabricated
      by hot embossing and thermal bonding, consists of eight parallel channels (10 mm
      long, 360 microm i.d.) connected via external fused-silica capillaries. The
      monomer mixture was aspirated simultaneously into the eight channels using a
      homemade vacuum manifold device and polymerized in parallel for 20 min under UV
      irradiation. The porous monolithic columns were then characterized by scanning
      electron microscopy and evaluated by ESI-MS applications with respect to sample
      capacity, recovery, reproducibility of peak area or peak height ratios, and
      linearity between peak height ratio and concentration using imipramine as a
      pharmaceutical test compound. The average sample capacity was estimated to be
      0.30 microg with a relative standard deviation (RSD) of 26.5% for the eight
      monolithic columns on the same polymeric chip. For two chips prepared using the
      same monomer mixture, the difference in average sample capacity was 7.0%. The
      average recovery for the eight monolithic SPE columns on the same chip was 79.1%
      with an RSD of 7.9%. Using imipramine-d3 as an internal standard, the RSD of peak
      height ratios for the eight different columns was 2.0% for a standard solution
      containing 1 microg/mL imipramine. A linear calibration curve (R2 = 0.9995) was
      obtained for standard aqueous solutions of imipramine in the range from 0.025 to
      10 microg/mL. To demonstrate the analytical potential of the chip-based SPE
      system, two different types of real-world samples including human urine sample
      and P450 drug metabolism incubation mixture were tested. Similar to standard
      aqueous solution, a linear correlation (R2 = 0.9995) was also found for human
      urine sample spiked with imipramine in the range of 0.025-10 microg/ mL. When
      aliquots of a human urine sample spiked with 1 microg/mL imipramine were loaded
      onto eight different monolithic columns, the RSD of peak height ratios was 3.8%.
      For a P450-imipramine incubation mixture, the formation of the N-demethylated
      metabolite (m/z 267.2) and the monohydroxylated metabolite (m/z 297.2) of
      imipramine was observed following chip-based monolithic SPE sample cleanup and
      preconcentration.

PMID- 14710833
TI  - Mass spectrometric characterization of functional poly(methyl methacrylate) in
      combination with critical liquid chromatography.
AB  - State-of-the-art techniques for the mass spectrometric characterization of
      synthetic polymers have been applied to functional poly(methyl methacrylate),
      synthesized by reversible addition-fragmentation chain-transfer (RAFT)
      polymerization. The polymers were first separated effectively according to
      functionality by liquid chromatography (LC) at the critical conditions (i.e.,
      almost no influence of molecular weight on retention). The separated polymers
      were characterized off-line by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS), and both off-line and on-line by LC
      electrospray-ionization-quadrupole-TOF-MS (LC-ESI-QTOF- MS). The on-line ESI
      experiments confirmed a clear baseline separation of the hydroxyl-functional
      prepolymers according to the number of hydroxyl groups. Labile end groups of
      PMMA, such as the dithioester group, were lost in the MALDI-TOF-MS experiments,
      while they were observed intact in the ESI-QTOF-MS spectra. This indicates that
      in the present case ESI is a much softer ionization technique than is MALDI. The
      ESI-MS experiments provided direct evidence that the RAFT polymers still
      exhibited living characteristics in the form of the dithio moiety.

PMID- 14710832
TI  - Application of molecular beam deflection time-of-flight mass spectrometry to
      peptide analysis.
AB  - The application of molecular beam deflection time-of-flight mass spectrometry
      (MBD-TOFMS) to peptide identification is described. The technique permits a
      simultaneous measurement of molecular mass and electric dipole susceptibility.
      The mass and susceptibility are not strongly correlated, and the results can be
      presented as a two-dimensional map. The susceptibility provides a useful way to
      disperse isobaric and isomeric peptides, and at least for small peptides, the
      susceptibility is significantly different for different amino acid sequences.
      Results for peptides in the mass range 1000-2300 Da show that the mass and
      susceptibility lead to a higher identification score than mass spectra alone.

PMID- 14710834
TI  - Polymer-coated fibrous materials as the stationary phase in packed capillary gas
      chromatography.
AB  - Synthetic polymer filaments have been introduced as the support material in
      packed capillary gas chromatography (GC). The filaments of the heat-resistant
      polymers, Zylon, Kevlar, Nomex, and Technora, were longitudinally packed into a
      short fused-silica capillary, followed by the conventional coating process for
      open-tubular GC columns. The separation of several test mixtures such as n
      alkylbenzenes and n-alkanes was carried out with these polymer-coated fiber
      packed capillary columns. With the coating by various polymeric materials on the
      surface of these filaments, the retentivity was significantly improved over the
      parent fiber-packed column (without polymer coating) as well as a conventional
      open-tubular capillary of the same length. The results demonstrated a good
      combination of Zylon as the support and poly(dimethylsiloxane)-based materials as
      the coating liquid-phase for the successful GC separation of n-alkanes and
      polycyclic aromatic hydrocarbons (PAHs), while successful applications for other
      separations such as poly(ethylene glycol) coating for the separation of alcohols
      were also obtained. From the results it has been suggested that the selectivity
      of the fiber-packed column could be tuned by selecting different coating
      materials, indicating the promising possibility for a novel usage of fine fibrous
      polymers as the support material that can be combined with newly synthesized
      coating materials specially designed for particular separations. Taking advantage
      of good thermal stability of the fibers, the column temperature could be elevated
      to higher than 350 degrees C with the combination of a short metallic capillary.

PMID- 14710835
TI  - Targeted multidimensional gas chromatography using microswitching and cryogenic
      modulation.
AB  - A new method is described that allows fast target analysis in multidimensional
      gas chromatography by using a microswitching valve between two GC columns, with
      cryogenic trapping and rapid re-injection of trapped solutes in the second
      dimension. The essence of the procedure is that heart-cut fractions from the
      first column (1D) can be selectively transferred to column 2 (2D), where a
      moveable cryogenic trap first focuses the transferred solute(s) at the head of
      the second column and then permits their facile rapid analysis on 2D. Since 2D is
      a short narrow-bore column, which exhibits very fast analysis (on the order of a
      few seconds elution), peak responses (heights) are significantly enhanced (by up
      to 40-fold). Additionally, by using a 2D phase of a selectivity different from
      that used for 1D, it is possible to also separate components that are not
      resolved on the first column and to increase the resolution for other compounds.
      The heart-cut valve isolates the section(s) of solutes of interest from the first
      column separation, and this provides a considerable simplification to the
      chromatogram-in addition to the separation and sensitivity advantages. By using
      this method, multidimensional gas chromatography with multiple heart-cuts can be
      completed within the same time as the primary column separation. Since the
      described method permits non-heart-cut fractions to be transferred to a monitor
      detector, normal detection of these fractions is still permitted. By modulation
      of the cryotrap, it is also possible to achieve comprehensive two-dimensional gas
      chromatography for the heart-cut fractions; however, only those compounds passed
      to the second, separation column, which passes through the cryotrap, will be
      subjected to GC x GC analysis. The technique and the various modes of operation
      are described in this paper.

PMID- 14710836
TI  - Development of water-based liquid chromatography at the critical condition.
AB  - Liquid chromatography at the critical condition (LCCC) is a chromatographic
      technique that allows for the isolation of one area of the polymer matrix so that
      other areas of the polymer may be probed with size-exclusion or adsorptive
      chromatographic modes. This technique has been successfully applied to the
      analysis of functionality distributions in functionalized oligomers and to
      polymer distributions within copolymers. Herein, the critical conditions of two
      polar polymers, poly(acrylic acid) and polystyrene sulfonate, are determined.
      These conditions were identified by varying buffer concentration, organic
      modifier within the mobile phase, or both. At the critical condition of
      poly(acrylic acid), the retention characteristics of a copolymer of acrylic acid
      and vinyl pyrrolidinone were determined. This extension to water-based mobile
      phase conditions will substantially broaden the possible applications of LCCC.

PMID- 14710837
TI  - Initial characterization of humic acids using liquid chromatography at the
      critical condition followed by size-exclusion chromatography and electrospray
      ionization mass spectrometry.
AB  - Structural information on humic acids is difficult to obtain because of the
      heterogeneity of the acids. Herein liquid chromatography at the critical
      condition, LCCC, is used to provide a sorting mechanism for the diverse types of
      molecules contained in humic acids. The critical condition of polymers that are
      believed to model some subunit of the humic acid is determined. Humic acids from
      three different terrestrial sources (soil, compost, and peat) are then separated
      under these chromatographic conditions. The portion of the humic acid that has
      structure similar to that of the model polymer elutes at the retention volume of
      the critical condition of the model. Next, fractions are collected and further
      characterized. This detailed characterization includes high-efficiency size
      exclusion chromatography and electrospray mass spectrometry. The size-exclusion
      chromatograms of the fractions were found to be markedly different from that of
      the original humic acid sample. This is strong evidence that the LCCC separation
      mechanism is different from size fractionation. The mass spectra of the humic
      acid fractions were also markedly different from those of the bulk humic acids
      previously reported. The mass spectra of specific fractions collected had
      repeating clusters of m/z values, which is more evidence that the critical
      condition separation is a powerful sort function.

PMID- 14710838
TI  - Nonaqueous capillary zone electrophoresis of synthetic organic polypeptides.
AB  - Poly(Nepsilon-trifluoroacetyl-L-lysine) was used as a model solute to investigate
      the potential of nonaqueous capillary electrophoresis (NACE) for the
      characterization of synthetic organic polymers. The information obtained by NACE
      was compared to that derived from size exclusion chromatography (SEC)
      experiments, and the two techniques were found to be complimentary for polymer
      characterization. On one hand, NACE permitted (i) the separation of oligomers
      according to their molar mass and (ii) the separation of the polymers according
      to the nature of the end groups. On the other hand, SEC experiments were used for
      the characterization of the molar mass distribution for higher molar masses. Due
      to the tendency of the solutes (polypeptides) to adsorb onto the fused-silica
      capillary wall, careful attention was paid to the rinsing procedure of the
      capillary between runs in order to keep the capillary surface clean. For that
      purpose, the use of electrophoretic desorption under denaturating conditions was
      very effective. Optimization of the separation was performed by studying (i) the
      influence of the proportion of methanol in a methanoVacetonitrile mixture and
      (ii) the influence of acetic acid concentration in the background electrolyte.
      Highly resolved separation of the oligomers (up to a degree of polymerization n
      of approximately 50) was obtained by adding trifluoroacetic acid to the
      electrolyte. Important information concerning the polymer conformations could be
      obtained from the mobility data. Two different plots relating the effective
      mobility data to the degree of polymerization were proposed for monitoring the
      changes in polymer conformations as a function of the number of monomers.

PMID- 14710839
TI  - A surface acoustic wave biosensor concept with low flow cell volumes for label
      free detection.
AB  - Special surface acoustic wave (SAW) devices using horizontally polarized surface
      shear waves can be operated in water. They allow an easy detection of molecules
      with biological relevance (e.g., proteins) via direct detection of the adsorbed
      mass. The transducer structures of conventional SAW devices are usually connected
      to the electronics by bond wires. In consequence, flow cell volumes can hardly be
      designed smaller than 50 microL. A new type of SAW device that is coupled
      capacitively with the electronics enables the reduction of flow cell volumes down
      to 60 nL, which decreases sample consumption and reduces the length of the
      measurement cycles down to a few minutes. To create an immunosensor, the SAW
      devices first are coated with a thin parylene layer for creating a sensor surface
      that is chemically homogeneous. Then OptoDex, a dextran containing both
      photoactive and functional groups is immobilized photochemically. Finally,
      antibodies are coupled via conventional EDC/NHS chemistry. The technique has been
      used to monitor urease binding at anti-urease-coated SAW devices in real time and
      with good resolution. Because of the simple sensor handling and the economical
      sample use, the new SAW device is particularly suitable for the design of an
      array.

PMID- 14710840
TI  - A method for monitoring the surface conservation of wooden objects by Raman
      spectroscopy and multivariate control charts.
AB  - The principles of quality control and multivariate statistical analysis were
      applied to the monitoring of the conservation state of wooden works of art. Three
      degradation processes (exposure to a wet atmosphere, to an acidic attack, and to
      UV light) were simulated on the surface of wooden boards of the XVI century and
      were monitored by the use of Raman spectroscopy. The resulting spectra were
      treated by principal component analysis, which allowed reduction of the system
      dimensionality. The relevant principal components were used to build multivariate
      control charts, namely, the Shewhart, CUSUM, and SMART (simultaneous scores
      monitoring and residual tracking) control charts. The Shewhart charts allowed
      identification of the effects due to the degradation processes. The CUSUM charts
      permitted identifcation of the exact moment in which the degradation treatment
      was started. The SMART charts provided a synthetic description of the
      conservation state of the wooden surface by means of only two charts: the T2
      Hotelling and the DModX charts.

PMID- 14710841
TI  - Compound-specific carbon isotope analysis of volatile organic compounds in the
      low-microgram per liter range.
AB  - Compound-specific carbon isotope analysis (CSIA) has become an important tool in
      biological, archeological, and geological studies as well as in forensics, food
      sciences, and organic chemistry. If sensitivity could be enhanced, CSIA would
      further have an improved potential for environmental applications such as, for
      example, in situ remediation studies to assess contaminated environments,
      identification of pollutant degradation pathways and kinetics, distinction
      between degradation/formation mechanisms, or, verification of contaminant
      sources. With this goal in mind, we have developed methods to determine delta13C
      values of commonly reported groundwater contaminants in low-microgram per liter
      concentrations. Several injection and preconcentration techniques were evaluated
      for this purpose, i.e., on-column injection, split/ splitless injection, solid
      phase microextraction (SPME), and purge and trap (P&T) in combination with gas
      chromatography-isotope ratio mass spectrometry. The delta13C values of the target
      compounds were determined by liquid injections of the analytes dissolved in
      diethyl ether or, in the case of P&T and SPME, by extraction from water spiked
      with the analytes. P&T extraction was the most efficient preconcentration
      technique reaching method detection limits (MDLs) from 0.25 to 5.0 microg/L.
      These are the lowest MDLs reported so far for continuous-flow isotope ratio
      determinations, using a commercially available and fully automated system.
      Isotopic fractionation resulting from preconcentration and injection was
      investigated and quantified for the priority groundwater pollutants methyl tert
      butyl ether (MTBE), chloroform, tetrachloromethane, chlorinated ethylenes,
      benzene, and toluene. The isotopic fractionations caused by the extraction
      techniques were small but highly reproducible and could therefore be corrected
      for. P&T was characterized by a higher reproducibility and smaller isotopic
      fractionations than SPME. Among the liquid injection techniques, cold on-column
      injection resulted in slightly better precision compared to split/splitless
      injection. However, the MDLs determined for liquid injections were 4-6 orders of
      magnitude higher (i.e., 9.5-2800 mg/L) than for P&T and SPME. Since both of the
      latter methods are solventless, a better chromatographic resolution was obtained
      than for the liquid injection techniques. The P&T and SPME methods described here
      are also applicable for CSIA of D/H ratios, which require 10-20 times higher
      analyte concentrations than 13C/12C analysis. Finally, the applicability of the
      described methods is demonstrated for pollutant concentrations of only 5-60
      microg/L in environmental samples.

PMID- 14710842
TI  - Species-specific isotope dilution with permeation tubes for determination of
      gaseous mercury species.
AB  - Instrumentation and methodology for determination of the gaseous mercury species
      Hg0, (CH3)2Hg, and CH3Hg+ has been developed. The method is based on continuous
      addition of gaseous isotopically enriched Hg species (tracers) at the point of
      sample acquisition, in combination with reduced pressure sampling on Carbotrap
      adsorbent tubes. Permeation tubes are used for generation of the tracers.
      Collected species are thermally desorbed and purged through an aqueous sodium
      tetraethylborate solution for derivatization of CH3Hg+. The purged gas is dried
      with a Nafion membrane, and the Hg species are subsequently collected on a
      smaller Tenax TA adsorbent tube. Species are then thermally desorbed from the
      Tenax TA and introduced into a gas chromatograph connected to an inductively
      coupled plasma mass spectrometer for separation and detection. To be able to add
      tracers during field sampling, we developed a portable device, supplying the
      permeation tubes with a thermostated and mass flow-controlled air stream of 5.0
      +/- 0.1 degrees C and 50.0 mL min(-1), respectively. Typical permeation rates
      obtained during a period of more than 6 weeks were 12.93 +/- 0.56, 0.42 +/- 0.01,
      and 0.49 +/- 0.03 (mean +/- standard deviation) pg of Hg min(-1) for a set of
      199Hg0, (CH3)2 198Hg, and CH3 200Hg+ tubes, respectively. Methodological
      detection limits (3sigma) were determined to 700 pg of Hg m(-3) for Hg0 and 50 pg
      of Hg m(-3) for (CH3)2Hg and CH3Hg+. The collection efficiencies for sampled
      volumes of 400 L of synthetic air on the Carbotrap tubes used in this study were
      13 +/- 2, 102 +/- 2, and 99 +/- 4% for Hg0, (CH3)2Hg, and CH3Hg+, respectively.
      Desorption efficiencies for the above species and tubes were 98 +/- 2, 98 +/- 1,
      and 90 +/- 4%, respectively. Fractions (20-40%) of the added (CH3)2 198Hg and CH3
      200Hg+ tracers were found to be transformed during the analytical processing of
      collected air samples. Determined concentrations in the research laboratory air,
      corrected for species transformations, were 3-53, 8-11, and 1-2 ng of Hg m(-3)
      for Hg0, (CH3)2Hg, and CH3Hg+, respectively. Concentrations in the ambient air
      were determined to be 2.1-2.6 ng m(-3) for Hg0 and below the detection limit for
      (CH3)2Hg and CH3Hg+.

PMID- 14710843
TI  - Modeling temperature-dependent protein structural transitions by combined near-IR
      and mid-IR spectroscopies and multivariate curve resolution.
AB  - The combination of near- and midinfrared spectroscopies (NIR and MIR) is proposed
      to monitor temperature-dependent transitions of proteins. These techniques offer
      a high discriminating power to distinguish among protein structural conformations
      but, in temperature-dependent processes, present the drawback associated with the
      intense and evolving absorption of the deuterium oxide, used as a solvent in the
      protein solutions. Multivariate curve resolution-alternating least squares (MCR
      ALS) is chosen as the data analysis technique able to unravel the contributions
      of the pure protein and deuterium oxide species from the mixed raw experimental
      measurements. To do so, MCR-ALS works by analyzing simultaneously experiments
      from MIR and NIR on pure deuterium oxide solutions and protein solutions in D2O.
      This strategy has proven to be effective for modeling the protein process in the
      presence of D2O and, therefore, for avoiding the inclusion of artifacts in the
      data stemming from inadequate baseline corrections. The use of MIR and NIR and
      MCR-ALS has been tested in the study of the temperature-dependent evolution of
      beta-lactoglobulin. Only the combined use of these two infrared techniques has
      allowed for the distinction of the three pure conformations involved in the
      process in the working thermal range: native, R-type state, and molten globule.

PMID- 14710844
TI  - Laser desorption combined with hyperthermal surface ionization time-of-flight
      mass spectrometry.
AB  - A setup combining laser desorption of nonvolatile molecules and their aerodynamic
      acceleration in a supersonic molecular beam followed by hyperthermal surface
      ionization in a reflectron time-of-flight mass spectrometer is described. While
      laser desorption performs the intact transfer of the analyte molecules into the
      gas phase, hyperthermal surface ionization opens up the possibility to
      efficiently ionize even larger molecules with a small and potentially controlled
      degree of fragmentation. Being an ionization technique, which is particularly
      effective for aromatic and heterocyclic compounds, the selectivity can further be
      increased by tuning the kinetic energy to which the molecules are accelerated in
      the supersonic beam. The results obtained for several polycyclic aromatic
      hydrocarbons and biochemical substances show that sufficient acceleration can be
      achieved even for molecules with a molecular weight above 5000 amu and that HSI
      preserves its advantageous features even for thermally labile large molecules
      such as insulin.

PMID- 14710845
TI  - MALDI analysis of Bacilli in spore mixtures by applying a quadrupole ion trap
      time-of-flight tandem mass spectrometer.
AB  - A novel ion trap time-of-flight hybrid mass spectrometer (qIT-TOF MS) has been
      applied for peptide sequencing in proteolytic digests generated from spore
      mixtures of Bacilli. The method of on-probe solubilization and in situ
      proteolytic digestion of small, acid-soluble spore proteins has been recently
      developed in our laboratory, and microorganism identification in less than 20 min
      was accomplished. In this study, tryptic peptides were generated in situ from
      complex spore mixtures of B. subtilis 168, B. globigii, B. thuringiensis subs.
      Kurstaki, and B. cereus T, respectively. MALDI analysis of bacterial peptides
      generated was performed with an average mass resolving power of 6200 and a mass
      accuracy of up to 10 ppm using a trap-TOF tandem configuration. Precursor ions of
      interest were usually selected and stored in the quadrupole ion trap with their
      complete isotope distribution by choosing a window of +/- 2 Da. Sequence-specific
      information on isolated protonated peptides was gained via tandem MS experiments
      with an average mass resolving power of 4450 for product ion analysis, and
      protein and bacterial sources were identified by database searching.

PMID- 14710846
TI  - Characterization of Bacillus spore species and their mixtures using postsource
      decay with a curved-field reflectron.
AB  - A strategy is proposed for the rapid identification of Bacillus spores, which
      relies on the selective release of a family of proteins, referred to as small,
      acid-soluble spore proteins (SASPs). In this work, SASPs were selectively
      solubilized from Bacillus spores on the MALDI sample plate by using 10% TFA.
      Proteolytic digests of SASPs generated in situ from spores of B. subtilis 168, B.
      globigii, B. thuringiensis subs. Kurstaki HD-1, B. cereus T, and the
      nonpathogenic strain B. anthracis Sterne were prepared in 5-25 min by using
      trypsin immobilized on Agarose beads and subsequently analyzed by MALDI-TOFMS
      using a curved-field reflectron. Protein identification was obtained by partial
      sequencing of distinctive tryptic peptides from Bacillus spores via post-source
      decay analysis combined with genome-based database searches by Mascot Sequence
      Query. Various unique SASPs were identified, allowing the characterization of
      Bacillus species by obtaining sequence-specific information on single peptides.
      The applicability of this approach for the rapid identification of Bacillus
      species was further established by analyzing spore mixtures.

PMID- 14710847
TI  - Determination of N-glycosylation sites and site heterogeneity in glycoproteins.
AB  - An approach for the characterization of glycosylation sites and oligosaccharide
      heterogeneity in glycoproteins based on a combination of nonspecific proteolysis,
      deglycosylation, and matrix-assisted laser desorption/ionization Fourier
      transform mass spectrometry (MALDI-FT MS) is described. Glycoproteins were
      digested with Pronase yielding primarily glycopeptides and amino acids.
      Nonglycosylated peptide fragments were susceptible to complete Pronase digestion
      to their constituent amino acids. Steric hindrance prohibited the digestion of
      the peptide moiety attached to the glycan. Glycopeptides were desalted and
      concentrated using solid-phase extraction and analyzed by MALDI MS. The
      oligosaccharides were also analyzed by MALDI MS after releasing the glycans from
      glycoproteins using PNGase F. The peptide moiety of the glycopeptides was
      identified by subtracting the masses of the glycans derived from PNGase F
      treatment from the masses of the glycopeptides. The experimental strategy was
      validated using glycoproteins with known oligosaccharide structures, ribonuclease
      B and chicken ovalbumin. This procedure was then used to determine the N
      glycosylation sites and site heterogeneity of a glycoprotein whose glycosylation
      pattern was unknown, namely, the Xenopus laevis egg cortical granule lectin. This
      procedure is useful for determining protein site heterogeneity and structural
      heterogeneities of the oligosaccharide moiety of glycoproteins.

PMID- 14710848
TI  - The presence of 19-kDa Bcl-2 in dividing cells.
AB  - The 26-kDa bcl-2 gene product inhibits apoptosis and cell proliferation. Cleavage
      of Bcl-2 into a 22-kDa fragment inactivates its anti-apoptotic activity and is a
      key event in apoptosis. Here, and in recent work, we describe massive 19-kDa Bcl
      2 immunoreactivity in non-apoptotic cells, suggesting a link with viability
      rather than cell death. Loss of 19 kDa Bcl-2 in adriamycin-induced apoptotic
      cells underlines this. G2/M-phase accumulation of cells by nocodazole-treatment
      also results in loss of 19 kDa Bcl-2. Next to its well-documented cytoplasmic
      localization, a substantial pool of Bcl-2 resides in nuclei. Hampered nuclear
      localization of Bcl-2 leads to a loss of cell cycle repression. This has led us
      to point at a pivotal role for nuclear Bcl-2 in cellular proliferation. In this
      report, cellular fractionation of bcl-2 transfected cells in various phases of
      the cell cycle reveals a constitutive cytoplasmic pool of 19 kDa Bcl-2. Nuclear
      19-kDa Bcl-2 immunoreactivity is far more pronounced in rapidly dividing nuclei
      compared with more quiescent nuclear fractions. This implicates that ongoing cell
      proliferation involves cleavage of nuclear Bcl-2 with a 19-kDa fragment.

PMID- 14710849
TI  - Stages of activation of hepatic stellate cells: effects of ellagic acid, an
      inhibiter of liver fibrosis, on their differentiation in culture.
AB  - To further explore that hepatic stellate cell (HSC) activation results in
      physiological protection against environmental insult, the profile of
      differentiation of HSC has been examined upon treatment with ellagic acid (EA), a
      plant-derived antioxidant that shows multiple protective effects during liver
      disease. Sparse rat liver cell cultures were grown in media containing EA (3, 6,
      30 and 100 microg/ml) and, as controls, without EA, and inspected until day 7 in
      culture. The cells were double-labelled with antibodies against glial fibrillary
      acidic protein (GFAP) and smooth muscle alpha-actin (SMAA), marker proteins of
      quiescent and activated HSC, respectively. In EA-free culture conditions, the
      quiescent (SMAA-/GFAP+) HSC transiently acquired a semi-activated (SMAA+/GFAP+),
      phenotype and were further transformed into activated (SMAA+/GFAP-), pleomorphic
      HSC. Up to a concentration of 30 microg/ml, EA induced an early synthesis of SMAA
      in all HSC and inhibited their morphologic differentiation and individual growth
      throughout the culture period. At a concentration of 6 microg/ml, EA supported
      the semi-activated (SMAA+/GFAP+) phenotype of HSC throughout the culture period,
      whereas treatment with high EA concentrations (30 microg/ml) resulted in an early
      loss of GFAP expression. IN CONCLUSION: (i) the uniform response of HSC to EA by
      mild activation adds functional significance to cellular features preceding the
      transformation of HSC to myofibroblasts; (ii) the high sensitivity of HSC to EA
      treatment suggests their involvement in any mechanisms of protection by this
      antioxidant; (iii) the maintenance of HSC morphology might be one of the factors
      playing a role in the prevention or slowing down of liver fibrosis; (iv) because
      the effects of EA are concentration- and time-dependent, an arbitrary usage of
      this antioxidant is a matter of potential concern; (v) the various patterns of
      HSC activation observed might correspond to distinct activities of these cells,
      which, in turn, might lead to different outcomes of liver fibrosis.

PMID- 14710850
TI  - Hypoxia-induced irreversible S-phase arrest involves down-regulation of cyclin A.
AB  - We have studied hypoxia-induced cell cycle arrest in human cells where the
      retinoblastoma tumour suppressor protein (pRB) is either functional (T-47D cells)
      or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). All
      cells in S phase are immediately arrested upon exposure to extreme hypoxia.
      During an 18-h extreme hypoxia regime, the cyclin A protein level is down
      regulated in cells of both types when in S-phase, and, as we have previously
      shown, pRB re-binds in the nuclei of all T-47D cells (Amellem et al. 1996).
      Hence, pRB is not necessary for the down-regulation of cyclin A during hypoxia.
      However, our findings indicate that re-oxygenation cannot release pRB from its
      nuclear binding following this prolonged exposure. The result is permanent S
      phase arrest even after re-oxygenation, and this is correlated with a complete
      and permanent down-regulation of cyclin A in the pRB functional T-47D cells. In
      contrast, both cell cycle arrest and cyclin A down-regulation in S phase are
      reversed upon re-oxygenation in non-pRB-functional NHIK 3025 cells after
      prolonged exposure to extreme hypoxia. Our results indicate that pRB is involved
      in permanent S-phase arrest and down-regulation of cyclin A after extreme
      hypoxia.

PMID- 14710851
TI  - Identification of differentially expressed genes in isogenic highly metastatic
      and poorly metastatic cell lines of R3230AC rat mammary adenocarcinoma.
AB  - Tumour metastasis occurs as a result of a cascade of events including alterations
      in the expression of various genes. The identification of such genes is essential
      to understanding formation of metastasis. In a previous study, highly metastatic
      (LN4.D6) and poorly metastatic (CAb.D5) cell lines were obtained from the rat
      mammary adenocarcinoma cell line R3230AC. Subtractive hybridization was used to
      identify differentially expressed genes between these two cell lines. We
      identified eight cDNA clones in CAb.D5 and six cDNA clones in LN4.D6 that were
      differentially expressed. One of the cDNA clones in each cell line had no
      homology with known sequences. Expression patterns of these differentially
      expressed genes were examined in a pair of rat mammary and prostate
      adenocarcinoma cell lines. Compared with cell lines examined, cDNA FF-10 was only
      expressed in CAb.D5; however, cDNA RB-8, RE-1, RF-5 were only expressed in the
      highly metastatic LN4.D6. No correlation was observed between expression patterns
      of the differentially expressed genes and metastatic potential of these cells.
      However, differential expression of genes, especially cytokeratins (CK8 and CK5)
      and collagens (III and IV) between highly metastatic and low metastatic rat
      mammary adenocarcinoma cell lines might initiate further investigation of these
      genes in metastatic process.

PMID- 14710852
TI  - Over-expression of cyclin D1 regulates Cdk4 protein synthesis.
AB  - Increased Cdk4 expression occurs coincident with over-expression of cyclin D1 in
      many human tumours and tumourigenic mouse models. Here, we investigate both in
      vivo and in vitro the mechanism by which Cdk4 expression is regulated in the
      context of cyclin D1 over-expression. Cdk4 mRNA levels in cyclin D1-over
      expressing tissue and cultured cells were unchanged compared with controls. In
      contrast, Cdk4 protein levels were increased in cyclin D1-over-expressing tissue
      and cells versus their respective controls. This increase was not due to altered
      protein stability, but appeared to be due to an increase in Cdk4 protein
      synthesis. We also performed immunoprecipitation and in vitro kinase assays to
      demonstrate an increase in cyclin D1-Cdk4 complex formation and associated kinase
      activity. Blocking cyclin D1 expression resulted in diminished Cdk4 protein but
      not mRNA levels. These findings suggest a mechanism by which Cdk4 expression is
      increased in the context of cyclin D1 over-expression during tumourigenesis.

PMID- 14710854
TI  - Serotypic and antibiotic susceptibility pattern of Salmonella species isolated
      from cases of gastroenteritis at Infectious Diseases Hospital (IDH), Delhi from
      1997-2000.
AB  - A total number of 11,551 stool samples/rectal swabs obtained from acute
      gastroenteritis cases admitted at Infectious Diseases Hospital (IDH), Delhi
      during a period of four years from 1997-2000 were processed at National Institute
      of Communicable Diseases (NICD), Delhi to look for the presence of
      enteropathogens. One hundred twelve Salmonellae species belonging to different
      serotypes were isolated. The commonest species was S. typhimurium, accounting for
      31% of isolates, followed by S. weltervreden (19%), S. litchfield (15%) and
      others. 61% of S. typhimurium isolates depicted multidrug resistance to
      Chloramphenicol, Tetracycline, Furazolidone and Co-trimoxazole. However, none
      showed resistance to quinolones and third generation cephalosporins. Estimation
      of minimum inhibitory concentration (MIC) for S. typhimurium against Ampicillin,
      Chloramphenicol and Cephalothin was carried out by E test. A good correlation
      between disc diffusion technique and E test was observed.

PMID- 14710853
TI  - Dietary pectin and calcium inhibit colonic proliferation in vivo by differing
      mechanisms.
AB  - Diet plays an important role in promoting and/or preventing colon cancer;
      however, the effects of specific nutrients remain uncertain because of the
      difficulties in correlating epidemiological and basic observations. Transmissible
      murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, causes
      significant hyperproliferation and hyperplasia in the mouse distal colon and
      increases the risk of subsequent neoplasia. We have recently shown that TMCH is
      associated with an increased abundance of cellular beta-catenin and its nuclear
      translocation coupled with up-regulation of its downstream targets, c-myc and
      cyclin D1. In this study, we examined the effects of two putatively protective
      nutrients, calcium and soluble fibre pectin, on molecular events linked to
      proliferation in the colonic epithelium during TMCH. Dietary intervention
      incorporating changes in calcium [high (1.0%) and low (0.1%)] and alterations in
      fibre content (6% pectin and fibre-free) were compared with the standard AIN-93
      diet (0.5% calcium, 5% cellulose), followed by histomorphometry and
      immunochemical assessment of potential oncogenes. Dietary interventions did not
      alter the time course of Citrobacter infection. Both 1.0% calcium and 6% pectin
      diet inhibited increases in proliferation and crypt length typically seen in
      TMCH. Neither the low calcium nor fibre-free diets had significant effect. Pectin
      diet blocked increases in cellular beta-catenin, cyclin D1 and c-myc levels
      associated with TMCH by 70%, whereas neither high nor low calcium diet had
      significant effect on these molecules. Diets supplemented with either calcium or
      pectin therefore, exert anti-proliferative effects in mouse distal colon
      involving different molecular pathways. TMCH is thus a diet-sensitive model for
      examining the effect of specific nutrients on molecular characteristics of the
      pre-neoplastic colonic epithelium.

PMID- 14710855
TI  - Knowledge, attitude and practices towards HIV among nurses in a tertiary care
      teaching hospital: two decades after the discovery.
AB  - Accidental transmission of HIV infection to health care workers during
      occupational exposure is a real threat today. The first such case in India has
      been documented by NACO recently. Adequate knowledge about the disease and
      practice of safety measures are our best bet to reduce such transmission. A
      survey was carried out amongst over 500 nurses in a tertiary care referral
      hospital in Delhi to assess their knowledge, attitude and practices towards
      HIV/AIDS. While overall knowledge was satisfactory, there were gaping holes in
      vital areas. The conversion of their theoretical knowledge into safe practices
      was shockingly poor. It was due to attitude problems as much as inadequate
      supplies. High incidence of accidental exposures in the near past and complete
      ignorance of post-exposure prophylaxis guidelines was another highlight of this
      study. Despite tremendous efforts put in by the Government as well as various Non
      Governmental Organizations, we are completely ill equipped to fight the menace of
      occupational HIV transmission. In order to fight this menace, "safe practices"
      have to be made a "way of life" for HCWs. Our health care planners need to take
      note of it and our teaching and training programmes need complete re-orientation
      to achieve this goal.

PMID- 14710856
TI  - Antibiotic sensitivity pattern of the bacteria isolated from nosocomial
      infections in ICU.
AB  - The incidence of nosocomial infections in ICU is 4-5 times greater than in
      general ward. Critically ill patients are always at higher risk of developing
      nosocomial infections with resistant strains. This study is an attempt to know
      the antibiotic sensitivity pattern of the common isolates in ICU. Samples
      comprising urine, blood, endotracheal secretions and throat swabs were collected
      from 102 ICU patients of them, 56 patients showed evidence of nosocomial
      infection (54.9%), from whom 120 different organisms were isolated. Antibiotic
      sensitivity test was done according to Kirby Bauer method. Klebsiella pneumoniae
      were the most prevalent isolates from respiratory tract infections followed by
      Proteus spp, Escherichia coli, Staphylococci spp. and Acinetobacter spp. The gram
      negative enteric bacilli were uniformly resistant to betalactam antibiotics as
      well as betalactam-betalactamase inhibitors. Resistance to Ciprofloxacin and
      Ceftriaxone ranged from 50-100% and 25-83.3% respectively. Staphylococci were
      100% resistant to penicillin and tetracycline, 80% to cotrimoxazole, 60% to
      erythromycin and gentamicin and 40% to amikacin. Acinetobacter spp. were highly
      resistant to most of the antibacterial agents except gentamicin while Pseudomonas
      spp. showed 75% resistance to it. The increased prevalence of resistant organisms
      in ICU probably reflects lack of proper antibiotic policy resulting in prolonged
      and indiscriminate use of antimicrobial agent.

PMID- 14710857
TI  - Larvicidal activity of latex and stem bark of Euphorbia tirucalli plant on the
      mosquito Culex quinquefasciatus.
AB  - The methanolic, chloroform and ether extracts of Euphorbia tirucalli latex and
      stem bark were evaluated for larvicidal activity against laboratory-reared larvae
      of Culex quinquefasciatus (Diptera: Culicidae), vector of the brancroftian
      filariasis and worst urban nuisance mosquito. The latex extracts contain more
      potent larvicidal components (177.14 mg/L-326.37 mg/L) than the stem bark
      extracts (237.663 mg/L-513.39 mg/L). The order of toxicity (LC50) for the latex
      extracts was Methanol extract (177.14 mg/L) > Chloroform (200.76 mg/L) > Ether
      (326.37 mg/L) while the rank of order of toxicity (LC50) of stem bark extracts
      was Ether (237.66 mg/L) > Chloroform (343.515 mg/L) > Methanol (513.387 mg/L),
      Higher doses (LC90 24 h of mosquito larvae) of each extract did not cause any
      mortality among fishes after 24 h. The study gave a weight into the possibility
      of formulating suitable preparation from the latex and stem bark extracts of the
      plant for use in mosquito control programme.

PMID- 14710858
TI  - First report of Vibrio cholerae infection from Andaman and Nicobar, India.
AB  - Out of 34 Stool Samples collected during an outbreak of diarrhoea, Vibrio
      cholerae 01 was isolated from 10 samples contrary to earlier reports that
      Shigella species was the only cause of diarrhoeal disease in Andaman & Nicobar
      Islands.

PMID- 14710859
TI  - Evaluation of a two step AFB cold staining method and simplified concentration
      technique for diagnosis of pulmonary tuberculosis.
AB  - Ziehl Neelsen (Z-N) stain is the commonly used procedure for demonstration for
      AFB. A Simple cold stain technique and Simplified concentration technique were
      compared with the conventional methods on 1484 sputum samples over a period of 3
      months. A positivity rate of 9.3% was observed on direct microscopy with an
      increase in the yield by 30% after concentration. It was observed that the simple
      cold staining and simplified concentration are viable alternatives for
      demonstration of mycobacteria in busy clinical laboratories.

PMID- 14710860
TI  - Intensified pulse polio immunisation coverage in slums of a metropolitan city: an
      appraisal.
AB  - A study was conducted by house-to-house visit during 2nd and 3rd round of IPPI in
      Nov and Dec 2000 in two slums adjacent to Medical College Kolkata. Total houses
      visited in these two rounds were 2836 and 611 children were immunised at home.
      Mothers of 503 children (who did not receive IPPI dose at booth on NIDs) were
      interviewed. For rest 104 children, mothers were not available during the time of
      visit. The result showed that infants were the largest group (30.6%) to receive
      vaccine at home. Majority (84.1%) was permanent residents of the locality. Only
      4.2% were Bengali-speaking Hindus while most other were Hindi or Urdu speaking
      Muslims. "Health workers will bring vaccine at door steps" was the reason of non
      attendance at booth by 30.2% parents. No routine immunisation was received by
      14.9% children. The source of information regarding IPPI was, 45.4% from medical
      students, 28.5% from health workers, 15.1% from TV, 5.6% from relatives and
      neighbours, 3.6% from miking and 1.8% from newspapers respectively.

PMID- 14710861
TI  - Human brucellosis: review of an under-diagnosed animal transmitted disease.
AB  - Human brucellosis is an important animal transmitted disease of man. Although,
      the cases have been recorded all over the world, the prevalence is higher in
      developing countries. Lack of sufficient knowledge about the disease among the
      physicians, its under-diagnosis or misdiagnosis and absence of effective
      prevention and management strategies are attributed to the widespread of the
      disease. Increase in the occurrence of animal brucellosis has also resulted
      indirectly in an increase in the prevalence of human infection. Absence of
      characteristic clinical symptoms, chronic nature of the infection and difficulty
      in isolation of the causal agent from the patients make the diagnosis of the
      disease more difficult. The serological tests employed for diagnosing human
      brucellosis vary in terms of their sensitivity and specificity. Therefore, a
      combination of serological tests is desirable. Currently no vaccine is available
      against human brucellosis, which could check the spread of the disease
      effectively. It is suggested that clinicians investigate the cases of pyrexia of
      unknown origin (PUO) for brucellosis. It is desirable that specimens from cases
      of tuberculosis, typhoid, rheumatoid arthritis, urogenital infections, kala-azar,
      cirrhosis, bacterial endocarditis, leukemia and filariasis should also be
      screened for brucellosis in man. The cases of meningitis of unestablished
      etiology as the cases of human brucellosis are often misdiagnosed as cases of
      typhoid or tuberculosis.

PMID- 14710862
TI  - A case report on self-cure of visceral leishmaniasis.

PMID- 14710863
TI  - An epidemiological surveillance of acute flaccid paralysis in Alwar district.

PMID- 14710864
TI  - [Inhibition and working memory: effect of acute sleep deprivation on a random
      letter generation task].
AB  - The literature contains inconsistent data on the effects of acute sleep
      deprivation on the superior cognitive functions. The primary purpose of this
      study is to determine the effectiveness of inhibition, one of the functions of
      the working memory executive centre (EC), over an extended, 36-hour waking
      period. Inhibition is a cognitive mechanism whereby individuals ignore non
      relevant information recorded in their working memory. We also tested the effects
      of a 36-hour period of acute sleep deprivation on simple reaction time. Twelve
      young, healthy volunteers (M = 21.5 years, sigma = 2.3) performed a random
      generation task involving letters and a simple reaction time psychomotor test
      over four sessions held at 10-hour intervals. Each participant was assigned a
      "constant routine." Participants were kept awake in a prone position within a
      room whose environment was held strictly constant (light, noise, temperature,
      meals, etc.). This control procedure provided assurance that any variation in
      participant performance was solely caused by sleep deprivation. The random
      generation task, nearly two minutes in length, consisted in verbally producing a
      sequence of 100 letters in a random fashion (i.e. by inhibiting, for example,
      alphabetical order) and by keeping to a set rhythm. Our assumption was that
      capacity for inhibition diminished as the number of hours of sleep deprivation
      increased. The simple reaction test, 10 minutes in length, involved pressing a
      button as swiftly as possible to cause a black square to disappear from a screen.
      In this case our assumption was that acute sleep deprivation alters simple
      reaction time. Analysis of variance (ANOVA) through repeated measures using the
      "sessions" factor as an intra-subject variable showed no significant changes in
      randomization indices of the random generation task, contrary to analysis of
      average simple reaction times. Participants' reaction times deteriorated over the
      first two minutes of the test during the night they were deprived of sleep. It
      would seem that the contradictory results of previous studies of the effects of
      acute sleep deprivation on the inhibition function would be due to errors in
      factor identification. In conclusion, the inhibition function, as measured during
      the performance of a brief task, seems to remain intact during an extended, 36
      hour waking period. Simple reaction time assessed by means of a brief psychomotor
      test is affected during a night of sleep deprivation. The working-memory
      inhibition executive function shows greater resistance to acute sleep deprivation
      than does psychomotor reaction time for the performance of short tasks.

PMID- 14710865
TI  - The effect of perceptual distinctiveness on the prospective and retrospective
      components of prospective memory in young and old adults.
AB  - In two experiments, the effect of perceptual distinctiveness of cues on
      prospective memory performance was examined. Young and older adults completed a
      visual search task with embedded prospective memory instructions. On each trial,
      participants were asked to indicate the position of a target letter in a letter
      string, unless either of two letters previously identified as prospective memory
      cues was presented. Each prospective cue was associated with a specific response.
      Perceptual distinctiveness was manipulated by spatially displacing a single
      letter. The prospective component (successful detection of the cue) and the
      retrospective memory component (recalling the correct response when a cue is
      detected) were measured separately. Perceptual displacement of cues modulated
      performance of the prospective component but not the retrospective component.
      Young adults successfully detected a larger proportion of cues (prospective
      component) than older adults. However, there were minimal effects of age and no
      effect of cue displacement on participants' ability to recall the intention once
      they detected a cue (retrospective component performance). Results are discussed
      within the context of current theoretical models of prospective memory.

PMID- 14710866
TI  - Examining the interactivity of lexical orthographic and phonological processing.
AB  - The number and type of connections involving different levels of orthographic and
      phonological representations differentiate between several models of spoken and
      visual word recognition. At the sublexical level of processing, Borowsky, Owen,
      and Fonos (1999) demonstrated evidence for direct processing connections from
      grapheme representations to phoneme representations (i.e., a sensitivity effect)
      over and above any bias effects, but not in the reverse direction. Neural network
      models of visual word recognition implement an orthography to phonology
      processing route that involves the same connections for processing sublexical and
      lexical information, and thus a similar pattern of cross-modal effects for
      lexical stimuli are expected by models that implement this single type of
      connection (i.e., orthographic lexical processing should directly affect
      phonological lexical processing, but not in the reverse direction). Furthermore,
      several models of spoken word perception predict that there should be no direct
      connections between orthographic representations and phonological
      representations, regardless of whether the connections are sublexical or lexical.
      The present experiments examined these predictions by measuring the influence of
      a cross-modal word context on word target discrimination. The results provide
      constraints on the types of connections that can exist between orthographic
      lexical representations and phonological lexical representations.

PMID- 14710867
TI  - [Differential effects of aging on processes involved in mental imagery
      generation].
AB  - The purpose of this study was to measure the degree to which the deterioration of
      mental image generation processes observed in elderly subjects by Dror and
      Kosslyn (1994) depends on the nature of the processing (referential vs.
      representational) involved in performing the task at hand. In keeping with the
      results of research showing that processing resources diminish as normal aging
      occurs (Craik & Bird, 1982; Rabinowitz, Craik & Ackerman, 1982), we suggest that
      generation ability based on referential processing is affected to a greater
      extent in older adults than is the generation ability involving representational
      processing. Fifteen young adults and 15 elderly persons performed a generation
      task modeled on that used by Dror and Kosslyn (1994). Observations were based on
      two contrasting conditions. In the first instance, subjects were required to
      generate an image representation of numbers when instructed to do so by a graphic
      stimulus, e.g., "31" (representational generation). In the second case,
      generation was produced on the basis of a verbal stimulus, e.g., "thirteen"
      (referential generation). Results (response time and number of accurate answers)
      show that, compared to young adults, elderly adults have a diminished ability to
      generate images based on words rather than numbers and do so at a slower pace.
      Our results suggest, therefore, that the performance of the first type of
      generation is cognitively more demanding for elderly subjects than that which is
      founded on figurative stimuli. The deterioration of mental image generation
      processes observed in elderly subjects by Dror and Kosslyn (1994) is therefore
      dependent on the nature of processing (referential vs. In conclusion we suggest
      two complementary assumptions to explain the observed dissociation. The
      differential effect of age may be the result of a deficienness cy linked to the
      nature of processing (control vs. automatic). Our second assumption is that, more
      specifically, referential generation involves more processing resources than does
      representational generation because it requires an additional transcoding
      operation. In this instance, the differential effect of aging that we observed
      would be closely linked to the number of cognitive operations involved in mental
      image generation.

PMID- 14710868
TI  - A paradigm for exploring what the mind does while deciding what it should do.
AB  - One widespread belief about automatic mental processes is that, among other
      characteristics, they are involuntary. No initial conscious intent is necessary
      because such processing is stimulus initiated. This claim was studied in the
      context of a novel task-choice procedure in which subjects were informed as to
      which of two tasks they should perform on a letter string either well in advance
      of a target, or when the target appeared. The hypothesis that initial processing
      of the target occurs without intent predicts that the effect of contrast
      reduction will be absent when the task cue appears synchronously with the target.
      This is because initial processing of the target should be completed during the
      time taken to decode the task cue. The results are inconsistent with this
      account. Instead, they support an account in which functional target processing
      is delayed until the subject knows what the task is. Some directions for future
      investigations are noted.

PMID- 14710869
TI  - Adults' understanding of inversion concepts: how does performance on addition and
      subtraction inversion problems compare to performance on multiplication and
      division inversion problems?
AB  - Problems of the form a + b - b have been used to assess conceptual understanding
      of the relationship between addition and subtraction. No study has investigated
      the same relationship between multiplication and division on problems of the form
      d x e / e. In both types of inversion problems, no calculation is required if the
      inverse relationship between the operations is understood. Adult participants
      solved addition/subtraction and multiplication/division inversion (e.g., 9 x 22 /
      22) and standard (e.g., 2 + 27 - 28) problems. Participants started to use the
      inversion strategy earlier and more frequently on addition/subtraction problems.
      Participants took longer to solve both types of multiplication/division problems.
      Overall, conceptual understanding of the relationship between multiplication and
      division was not as strong as that between addition and subtraction. One
      explanation for this difference in performance is that the operation of division
      is more weakly represented and understood than the other operations and that this
      weakness affects performance on problems of the form d x e / e.

PMID- 14710870
TI  - President signs bill assisting veterinary graduates with debt load. Student loan
      repayment offered to veterinarians working in underserved areas.

PMID- 14710871
TI  - Thoughts on laboratory animal veterinarians.

PMID- 14710872
TI  - Believes AVMA stance on antimicrobials too stagnant.

PMID- 14710873
TI  - What is your diagnosis? Avulsion fracture of the plantar aspect of the distal end
      of the calcaneus and plantar proximal intertarsal subluxation.

PMID- 14710874
TI  - Management strategies to decrease calf death losses in beef herds.

PMID- 14710875
TI  - Current approved drugs for aquatic species.

PMID- 14710876
TI  - Duration of serologic response to five viral antigens in dogs.
AB  - OBJECTIVE: To determine whether vaccinated dogs either remained seropositive or
      responded serologically to revaccination for 5 key viral antigens after extended
      periods since their last vaccination. DESIGN: Serologic survey. ANIMALS: 322
      healthy client-owned dogs. PROCEDURE: Dogs were > or = 2 years old and vaccinated
      against canine distemper virus (CDV), canine adenovirus-1 (CAV-1), canine
      adenovirus-2 (CAV-2), canine parainfluenza virus (CPIV), and canine parvovirus
      (CPV). On day 0, dogs were revaccinated with a vaccine from the same vaccine line
      as they had historically received. Antibody titers were measured in sera
      collected at day 0 (prevaccination titer) and 5 to 7 days later (postvaccination
      titer). Dogs were considered to have responded serologically if they had a day-0
      serum neutralization titer to CDV > or = 1:32; a serum neutralization titer to
      CAV-1, CAV-2, or CPIV > or = 1:16; a hemagglutination inhibition titer to CPV >
      or = 1:80; or a > or = 4-fold increase in antibody titer after revaccination.
      RESULTS: The percentage of dogs that had titers at or greater than the threshold
      values or responded to revaccination with a > or = 4-fold increase in titer was
      98.1% for CDV, 98.4% for CAV-1, 99.0% for CAV-2, 100% for CPIV, and 98.1% for
      CPV. CONCLUSIONS AND CLINICAL RELEVANCE: In most dogs, vaccination induced a
      response that lasted up to and beyond 48 months for all 5 antigens. Although not
      equivalent to challenge-of-immunity studies as a demonstration of efficacy,
      results suggest that revaccination with the same vaccine provides adequate
      protection even when given less frequently than the traditional 1-year interval.
      The study provides valuable information for clinicians to help determine
      appropriate revaccination intervals.

PMID- 14710877
TI  - Duration of serologic response to three viral antigens in cats.
AB  - OBJECTIVE: To determine whether vaccinated cats either remained seropositive or
      responded serologically to revaccination against 3 key viral antigens after
      extended periods since their last vaccination. DESIGN: Serologic survey. ANIMALS:
      272 healthy client-owned cats. PROCEDURE: Cats were > or = 2 years old and
      vaccinated for feline panleukopenia virus (FPV), feline calicivirus (FCV), and
      feline herpesvirus (FHV). On day 0, cats were revaccinated with a vaccine from
      the same line of vaccines as they had historically received. Antibody titers were
      measured in sera collected on day 0 (prevaccination titer) and 5 to 7 days later
      (postvaccination titer). Cats were considered to have responded serologically if
      they had a day-0 hemagglutination inhibition titer to FPV > or = 1:40, serum
      neutralization (SN) titer to FCV > or = 1:32, SN titer to FHV > or = 1:16, or >
      or = 4-fold increase in antibody titer after revaccination. RESULTS: The
      percentage of cats that had titers at or above the threshold values or responded
      to revaccination with a > or = 4-fold increase in titer was 96.7% for FPV, 97.8%
      for FCV, and 88.2% for FHV. CONCLUSIONS AND CLINICAL RELEVANCE: In most cats,
      vaccination induced a response that lasted up to and beyond 48 months for all 3
      antigens. Although not equivalent to challenge-of-immunity studies as a
      demonstration of efficacy, results suggest that revaccination with the vaccine
      used in our study provides adequate protection even when given less frequently
      than the traditional 1-year interval. The study provides valuable information for
      clinicians to determine appropriate revaccination intervals.

PMID- 14710878
TI  - Cardiorespiratory effects of epidural administration of morphine and fentanyl in
      dogs anesthetized with sevoflurane.
AB  - OBJECTIVE: To determine the cardiorespiratory effects of epidural administration
      of morphine alone and in combination with fentanyl in dogs anesthetized with
      sevoflurane. DESIGN: Prospective study. ANIMALS: 6 dogs. PROCEDURE: Dogs were
      anesthetized with sevoflurane and allowed to breathe spontaneously. After a
      stable plane of anesthesia was achieved, morphine (0.1 mg/kg [0.045 mg/lb]) or a
      combination of morphine and fentanyl (10 microg/kg [4.5 microg/lb]) was
      administered through an epidural catheter, the tip of which was positioned at the
      level of L6 or L7. Cardiorespiratory variables were measured for 90 minutes.
      RESULTS: Epidural administration of morphine alone did not cause any significant
      changes in cardiorespiratory measurements. However, epidural administration of
      morphine and fentanyl induced significant decreases in diastolic and mean
      arterial blood pressures and total peripheral resistance. Stroke volume was
      unchanged, PaCO2 was significantly increased, and arterial pH and base excess
      were significantly decreased. Heart rate was significantly lower after epidural
      administration of morphine and fentanyl than after administration of morphine
      alone. None of the dogs had any evidence of urine retention, vomiting, or
      pruritus after recovery from anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that epidural administration of morphine at a dose of 0.1 mg/kg
      in combination with fentanyl at a dose of 10 microg/kg can cause
      cardiorespiratory depression in dogs anesthetized with sevoflurane.

PMID- 14710879
TI  - Effects of a whole-body spandex garment on rectal temperature and oxygen
      consumption in healthy dogs.
AB  - OBJECTIVE: To determine whether a full-body spandex garment would alter rectal
      temperatures of healthy dogs at rest in cool and warm environments. DESIGN:
      Prospective study. ANIMALS: 10 healthy dogs. PROCEDURES: Each dog was evaluated
      at a low (20 degrees to 25 degrees C [68 degrees to 77 degrees F]) or high (30
      degrees to 35 degrees C [86 degrees to 95 degrees F]) ambient temperature while
      wearing or not wearing a commercially available whole-body spandex garment
      designed for dogs. Oxygen consumption was measured by placing dogs in a flow
      through indirect calorimeter for 90 to 120 minutes. Rectal temperature was
      measured before dogs were placed in the calorimeter and after they were removed.
      RESULTS: Rectal temperature increased significantly more at the higher ambient
      temperature than at the lower temperature and when dogs were not wearing the
      garment than when they were wearing it. The specific rate of oxygen consumption
      was significantly higher at the lower ambient temperature than at the higher
      temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that wearing a
      snug spandex body garment does not increase the possibility that dogs will
      overheat while in moderate ambient temperatures. Instead, wearing such a garment
      may enable dogs to better maintain body temperature during moderate heat loading.
      These results suggest that such garments might be used for purposes such as wound
      or suture protection without causing dogs to overheat.

PMID- 14710880
TI  - Accuracy of ultrasound-guided fine-needle aspiration of the liver and cytologic
      findings in dogs and cats: 97 cases (1990-2000).
AB  - OBJECTIVE: To evaluate the accuracy of ultrasound-guided fine-needle aspiration
      of the liver and cytologic findings in dogs and cats. DESIGN: Retrospective
      study. ANIMALS: 56 dogs and 41 cats. PROCEDURE: Medical records of dogs and cats
      evaluated from 1990 to 2000 by use of cytologic and histopathologic examination
      of the liver were reviewed. Histologic and cytologic diagnoses were categorized
      as vacuolar hepatopathy, inflammation, neoplasia, cirrhosis, primary cholestasis,
      shunt, normal, and other. RESULTS: Overall agreement between the histopathologic
      diagnosis and cytologic diagnosis was found in 17 of the 56 (30.3%) canine cases
      and 21 of the 41 (51.2%) feline cases. Vacuolar hepatopathy was the category with
      the highest percentage of agreement. Vacuolar hepatopathy was identified via
      cytologic examination in 7 of 11 and 15 of 18 dogs and cats, respectively, in
      which histopathologic examination revealed that it was the predominant disease
      process. However, it was also the category that was most commonly misdiagnosed
      via cytologic examination. Inflammatory disease was accurately identified
      cytologically in 5 of 20 and 3 of 11 dogs and cats, respectively. CONCLUSIONS AND
      CLINICAL RELEVANCE: Acknowledging the limitations of cytology and the extent of
      discrepancies between cytologic and histopathologic findings in dogs and cats
      will help clinicians make better decisions in diagnosing liver disease.

PMID- 14710881
TI  - Efficacy of radiation therapy for incompletely resected grade-III mast cell
      tumors in dogs: 31 cases (1987-1998).
AB  - OBJECTIVE: To determine the efficacy (durations of remission and survival) of an
      alternating-day radiation protocol for incompletely excised histologic grade-III
      solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS:
      31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol)
      was delivered to an area bordered by margins > or = 3 cm around the surgical scar
      and to the associated local-regional lymph nodes. Dogs were not given
      chemotherapeutic agents concurrently or after radiation. Information on
      signalment, duration of remission, and survival time was obtained from medical
      records. RESULTS: Median and mean durations of remission were 27.7 and 17.0
      months, respectively (range, 1 to 47 months). Median and mean durations of
      survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with
      tumors located on the skin of the pinna, perineum, and prepuce had a median
      duration of remission greater than dogs with tumors located at other sites (27.7
      and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter
      before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months,
      respectively). The remission rate was 65% and survival rate was 71% at 1 year
      after treatment. Sixteen dogs that were euthanatized had complications associated
      with local-regional tumor progression. Systemic metastases to liver, spleen,
      intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL
      RELEVANCE: Without further treatment, incompletely excised grade-III mast cell
      tumors have high local-regional recurrence; local-regional treatment with
      radiation may effectively be used to manage many such tumors.

PMID- 14710882
TI  - Flow cytometric detection of platelet-bound antibody in three horses with immune
      mediated thrombocytopenia.
AB  - Immune-mediated thrombocytopenia (IMT) is a sporadic cause of thrombocytopenia in
      horses for which it is difficult to establish a definitive diagnosis. In this
      report, we describe 3 horses with severe thrombocytopenia in which flow
      cytometric analysis of platelets for surface-bound IgG was used in an attempt to
      substantiate a provisional diagnosis of IMT. A distinct proportion (4.28%, 5.04%,
      and 7.95%) of platelets with surface-bound IgG was detected in the 3
      thrombocytopenic horses, but not in 6 healthy horses (0.03% to 0.15%) or 6 horses
      with colic (0.00% to 1.21%). These results, in conjunction with elimination of
      other potential causes of the thrombocytopenia, established a diagnosis of IMT.
      The horses were treated with glucocorticoids alone or in combination with
      azathioprine, and the thrombocytopenia gradually resolved. Flow cytometric
      detection of platelet-bound IgG was readily performed and may be a useful adjunct
      for the diagnosis of IMT.

PMID- 14710883
TI  - Scintigraphic abnormalities of the pelvic region in horses examined because of
      lameness or poor performance: 128 cases (1993-2000).
AB  - OBJECTIVE: To identify scintigraphic abnormalities in the pelvic region of horses
      examined because of hind limb lameness or poor performance and determine the
      clinical relevance of areas of abnormal radiopharmaceutical uptake (ARU) in these
      horses. DESIGN: Retrospective study. ANIMALS: 128 horses. PROCEDURE: Medical
      records were reviewed, and information on signalment, history, admitting
      complaints, physical examination findings, and results of lameness examinations
      was recorded. Clinical relevance of areas of ARU was determined by comparison
      with results of other diagnostic tests. For horses with clinically relevant areas
      of ARU, follow-up information was obtained through telephone interviews with
      owners and trainers and analysis of race records. RESULTS: Areas of ARU were
      identified in the tuber coxae (25 horses), ischiatic tuber (9), hip joint (10),
      third trochanter (10), ilium (5), sacral tuber region (22), greater trochanter
      (1), cranial femoral cortex (1), skeletal muscle surrounding the pelvis (34), or
      multiple areas (11). In 44 horses, areas of ARU were associated with the primary
      cause of lameness; in 51, areas of ARU were not associated with the primary cause
      of lameness; and in 33, the primary cause of lameness was not determined. Thirty
      six of the 44 horses with clinically relevant areas of ARU were available for
      follow-up; 15 (42%) had a good outcome. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that pelvic scintigraphy may be useful in identifying
      abnormalities in horses with hind limb lameness or poor performance.

PMID- 14710884
TI  - Hypomagnesemia among cows in a confinement-housed dairy herd.
AB  - Between January and March 2002, 55 cows in a 1,200-cow commercial dairy herd in
      south Florida died. Most of the cows that were found dead did not have any
      clinical signs of disease prior to death. Because of a history of a feed change,
      a bloom of blue-green algae in cow cooling ponds, and initial necropsy findings
      of moderate enteritis, the preliminary differential diagnosis included
      clostridial enteritis, blue-green algae toxicosis, and mycotoxicosis. Rumen
      acidosis, hypomagnesemia, and heavy metal toxicosis were included as secondary
      considerations. On the basis of physical examination and gross necropsy findings,
      results of clinicopathol ogic testing, and results of feed and water analyses, a
      diagnosis of hypomagnesemia was made. Control procedures that were implemented
      included changing the forage source and increasing the magnesium concentration in
      the diet.

PMID- 14710885
TI  - Histopathology and genetics of cutaneous T-cell lymphoma.
AB  - There is emerging evidence that genomic and chromosomal instability are features
      of CTCL, including variants such as MF, Sezary syndrome, and primary cutaneous
      CD30+ LCAL, and that specific chromosomal abnormalities are common. Additional
      resolution of specific regions of chromosomal loss and gain are required to
      define putative genes that may be of fundamental pathogenetic importance in CTCL.
      Inactivation of well-defined cell cycle and TSG are common as for other types of
      NHL. The prognostic significance of these abnormalities in CTCL has yet to be
      determined. The dysregulation of specific transcription factors is of interest,
      but requires further study. It is hoped that greater understanding of these
      molecular abnormalities will permit the development of CTCL-specific therapies
      that alleviate suffering and prolong survival.

PMID- 14710886
TI  - Immunopathogenesis of cutaneous T-cell lymphomas.
AB  - The physiopathology of cutaneous T-cell lymphomas is poorly understood. Little is
      known about the factors that drive a mature T-cell clone to accumulate in the
      skin, despite the feedback mechanisms that normally control immune response. This
      article discusses the identification of tumor-specific antigens.

PMID- 14710887
TI  - Primary cutaneous CD30-positive lymphoproliferative disorders.
AB  - Primary cutaneous CD30-positive (anaplastic) large T-cell lymphoma and
      lymphomatoid papulosis have many overlapping clinical, histologic, and
      immunophenotypic features. These entities are currently considered as parts of a
      spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. We
      provide the clinician with practical guidelines for the diagnosis, management,
      and treatment of patients within this spectrum of primary cutaneous CD30-positive
      lymphoproliferative disorders. Most patients within this spectrum of disease have
      an excellent prognosis. Multi-agent chemotherapy should be reserved for patients
      who have extracutaneous disease.

PMID- 14710888
TI  - Primary cutaneous B-cell lymphomas: a practical approach.
AB  - PCBCL are a heterogeneous group of B-cell lymphomas that originate in the skin,
      with the absence of extracutaneous disease at diagnosis. Overall, these cutaneous
      lymphomas have an excellent prognosis. Recurrences are common but dissemination
      is rare. The EORTC classification allows a more uniform diagnosis and treatment
      of patients with PCBCL. Careful clinical and pathologic correlation is critical
      in confirming a diagnosis of PCBCL, before deciding on therapy. Several
      therapeutic options that are aimed at cure, are available. In most instances,
      chemotherapy should not be the first line of treatment.

PMID- 14710889
TI  - Peripheral T-cell lymphomas: diagnosis and management.
AB  - Peripheral T-cell lymphomas are a diverse group of diseases with varying clinical
      manifestations. Response to conventional chemotherapy generally is poor.
      Treatment using purine analogs has achieved response rates between 25% and 60% in
      relapsed/refractory patients, with minimal toxicity. The highest response rates
      were seen with pentostatin and gemcitabine. Using purine analogs in combination
      therapy may improve response rates, albeit with an increased risk of toxicity.
      The role of purine analogs as first line therapy in patients who have otherwise
      favorable prognostic factors has not been defined. Monoclonal antibody therapy
      has emerged in the last decade as a promising approach in treating T-cell
      malignancies. Campath-1H is an effective and well-tolerated therapy in these
      diseases. Durable remissions have been seen in heavily pretreated patients and in
      up to two thirds of patients who had T-PLL, which is the largest disease group
      studied. These results in T-PLL are significantly better than those reported with
      other therapies; this suggests that Campath-1H should be moved to first line
      therapy in this aggressive disease. The way in which monoclonal antibodies work
      indicate that they may be particularly useful in treating patients who have
      minimal residual disease, and, in this setting, facilitate stem cell
      transplantation. In addition, the activity of Campath-1H to deplete T cells has
      been exploited in preparative regimens before allogeneic bone marrow
      transplantation. These approaches may be worth further investigation in patients
      who have T-cell lymphomas. None of the therapies that are available to treat the
      mature T-cell neoplasms seems to be curative, other than in selected patients who
      have favorable ALCL. Much of the data have been drawn from small, non-randomized
      studies. There is a need for larger, prospective, randomized trials to examine
      these novel therapies and to further explore combination regimens, which may
      exploit potential synergism.

PMID- 14710890
TI  - The Sezary syndrome: hematologic criteria.
AB  - The hematologic criteria for Sezary syndrome that were recently proposed by the
      International Society on Cutaneous Lymphomas are critically evaluated. Based on
      the experience at two institutions, revisions to the definition for Sezary
      syndrome are proposed.

PMID- 14710891
TI  - Selective immmunotherapy through extracorporeal photochemotherapy: yesterday,
      today, and tomorrow.
AB  - ECP's extensive clinical record, as well as a considerable improvement in the
      understanding of the mechanism that underlies its efficacy, opens potential novel
      strategies for the treatment of cancer, GVHD, transplant rejection, and
      autoimmunity. The low side effect profile of this therapy has made it a more
      attractive treatment consideration than current conventional chemotherapeutic and
      immunosuppressive medications. As the mechanism of action of ECP is more fully
      elucidated and clinical studies are completed, the role of ECP in modern
      therapeutics of CTCL and other malignancies, as well as in the treatment of other
      T-cell mediated diseases, will be become clearer.

PMID- 14710892
TI  - Topical and systemic retinoid therapy for cutaneous T-cell lymphoma.
AB  - Because curative therapies for CTCL are not yet available, short of TSEB in
      patients who have early-stage disease and allogeneic bone marrow transplantation
      in patients who have more advanced disease, the goal of current therapies is to
      prevent progression of MF and to preserve quality of life. The overall conclusion
      drawn from the studies reported in the literature, is that retinoids as
      monotherapy, or in combination with other nonaggressive treatment modalities,
      represent a low-risk treatment alternative that is especially suitable for
      controlling early stages of MF and other CTCL. A combination of therapies may be
      more effective in controlling CTCL as shown with IFN-alpha plus retinoids, and,
      recently, IFN-alpha with bexarotene and other modalities. For example,
      isotretinoin, followed by TSEB (for stage I to II disease) or preceded by
      chemotherapy (for stage II and IV disease) and bexarotene plus PUVA or
      photopheresis plus IFN, gave overall response rates of 82% and 69% in patients
      who had MF and SS, respectively. Retinoids as monotherapy may induce complete
      remissions, but usually these responses are of short duration and relapses are
      common. Clinical response is not identical to histologic clearance. Even in cases
      with clinically complete clearance of skin lesions, lymphoid infiltrates
      persisted, which are most likely the source of recurrences. The new generation of
      retinoids, the RXR selective agonists like bexarotene, represent a promising
      approach for refractory or persistent MF that is unresponsive to first-line
      therapies. Individual differences in response to retinoids may be due to
      different expression of retinoid receptors, functional polymorphisms in
      metabolizing retinoids, or resistance to some retinoids. In the future,
      pharmacogenomic studies are needed to clarify the mechanisms that underlie the
      differing response rates of patients who have CTCL to retinoids. In addition, new
      agonists of RAR and RXR, either selective or pan agonists, will become available
      and will enlarge the spectrum of vitamin A analogs that have antitumoral
      properties.

PMID- 14710893
TI  - Total skin electron beam radiotherapy for patients who have mycosis fungoides.
AB  - It has taken four decades of basic and clinical research to bring about a
      consensus process and published report that recognize a TSEB radiotherapy
      technique that is optimized from several perspectives (see references [2-4, 13]).
      Short and long-term clinical results with consensus TSEB radiotherapy technique
      are good. The therapeutic ratio of TSEB radiotherapy is well-defined and is
      clinically acceptable. Meanwhile, adjuvant PUVA and ECP may significantly improve
      results, but further data are needed to confirm these preliminary findings (see
      references [23, 34, 39, 40, 42]).

PMID- 14710894
TI  - Cytokine therapy of cutaneous T-cell lymphoma: interferons, interleukin-12, and
      interleukin-2.
AB  - It is well accepted that cutaneous T-cell lymphomas (CTCL), including mycosis
      fungoides and Sezary syndrome, represent lymphomas that are highly responsive to
      immune modifying agents. Furthermore, the recent emphasis on the use of cytokine
      related therapeutics is based upon the exceedingly important role of the host
      immune response in effecting progression of disease. In this article we discuss
      the data that support the importance of the host immune response in the control
      of progression of CTCL and the role that cytokine therapy has in supporting the
      host immune response and the effects of this approach to induce regression of
      skin and systemic disease.

PMID- 14710895
TI  - Interleukin-2 receptor-directed therapies for cutaneous lymphomas.
AB  - Our emerging understanding of the IL-2/IL-2R system opens the possibility for
      more specific immunotherapy of CTCL. This understanding, taken in conjunction
      with the ability to produce humanized antibodies to the IL-2R subunit by genetic
      engineering; to arm these antibodies, as well as IL-2 itself with toxins or with
      alpha- and beta-emitting radionuclides; and to modulate IL-2R subunits to
      optimize targeting of these agents provides a rational therapeutic strategy for
      the treatment of IL-2R-expressing CTCL. Although most of these studies were
      conducted in HTLV-1-associated T-cell lymphomas or CTCL, it is likely that these
      agents may be applicable to other T-cell lymphomas, including the anaplastic
      large cell lymphomas, peripheral T-cell lymphomas, and the natural killer
      lymphomas, because these cells express the IL-2 receptor.

PMID- 14710896
TI  - Novel agents for cutaneous T-cell lymphoma.
AB  - Several novel therapies have recently emerged for the treatment of hematologic
      malignancies; several agents have demonstrated activity against T-cell lymphomas
      in vitro or in early clinical trials. This article discusses how these therapies
      may be implemented in the treatment of patients who have advanced or refractory
      cutaneous T-cell lymphoma.

PMID- 14710898
TI  - High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma.
AB  - Although most patients who have cutaneous T-cell lymphoma have an indolent
      clinical course, patients who have cutaneous tumors, lymph node or visceral
      involvement, or peripheral blood involvement generally have rapidly progressive
      disease with shorter survival. In those patients with poor prognostic features,
      conventional combination chemotherapy is usually ineffective. High-dose
      chemotherapy with autologous hematopoietic stem cell transplant (HSCT) results in
      high remission rates, but the recurrence is inevitable and rapid. Allogeneic
      HSCT, in contrast, provides durable long-term remissions and is currently the
      only potentially curative therapy.

PMID- 14710897
TI  - Vaccine therapy for cutaneous T-cell lymphoma.
AB  - We demonstrated that percutaneous peptide immunization by way of skin with
      impaired barrier function is a simple and noninvasive strategy to generate
      effective immune responses against tumors. This therapeutic strategy seems to be
      beneficial for the treatment of skin-associated malignancies, including CTCL,
      because specific CTLs are considered to be well-induced in lymph nodes that
      neighbor barrier-disrupted skin (Fig. 3). There remain unsolved issues concerning
      (1) the ability of cytokines and growth factors to enhance efficacy of this
      therapy and (2) the time schedule of clinical trials. It was recently shown that
      application of antigenic protein or its coding DNA to skin with increased
      permeability yields antigen-specific antibody responses. Because the skin
      represents an easily accessible site for immunization and vaccination,
      percutaneous immunization using corneum barrier-disrupted skin is an alternative
      to injection of CTL-inducing molecules and can readily be exploited for cancer
      treatment in humans. The effective induction of CTLs suggests that the method
      that uses barrier-disrupted skin can potentially be applied to treatments of
      virus and helminth infections with the use of certain antigenic peptides.

PMID- 14710899
TI  - Prognosis, clinical outcomes and quality of life issues in cutaneous T-cell
      lymphoma.
AB  - Although the need for a specific QOL index for MF/SS has been recognized, little
      work has been done in this area. QOL instruments should address general health
      concepts, as well as specific issues that are relevant to patients who have
      MF/SS; a combination of two instruments may be appropriate. Confirming the
      validity, reliability, and responsiveness to change of a combination of QOL
      instruments, such as SKINDEX-29 and FACT-G, in patients who have MF/SS will be
      relevant. For patients who have MF/SS, focusing our efforts on improving the
      disease and their QOL should translate into improvements that are meaningful to
      them. Thus, our goal should be to incorporate the findings of QOL research into
      practice and use the results to guide our practices, as they relate to therapy.
      Some important considerations are: We must be explicit about what will be done
      with the information that is obtained about an individual's QOL. We should
      consider what additional knowledge QOL measures provide that we could not
      otherwise have. We should be ready for unexpected results, as exemplified by
      instances where aggressive therapy could result in improved QOL. Although
      challenges exist in moving forward QOL research in CTCL, the words of wisdom of
      Tannock bring the concept of QOL into perspective: "When cure remains elusive, it
      is time to start treating the patient, not just the tumor." A final consideration
      is that we should not forget the dimension of spirituality, which is especially
      relevant to patients who have advanced MF/SS. Spirituality is characterized by
      the capacity to seek purpose and meaning, to have faith, to love, to forgive, and
      to see beyond current circumstances. Spirituality enables a person to rise above
      suffering. Unfortunately, research on spirituality is scarce, in part, because of
      the difficulty in assessing spiritual suffering. Nevertheless, physicians who are
      caring for patients who have advanced MF/SS should acknowledge the spiritual
      dimension as an integral component of the dying process.

PMID- 14710900
TI  - Percutaneous tracheotomy.

PMID- 14710901
TI  - Interaction between the hypothalamic-pituitary-adrenal axis and behavioural
      compensation following unilateral vestibular deafferentation.
AB  - Vestibular compensation is defined as the process of behavioural recovery that
      occurs following the loss of sensory input from one or both vestibular
      labyrinths. The visual and postural instability resulting from the vestibular
      damage must alter the homeostasis of the subject; however, very little research
      has been conducted that investigates the interaction between vestibular
      compensation and the adaptive stress response of the body, i.e. the hypothalamic
      pituitary-adrenal (HPA) axis. The aim of this review is to describe and evaluate
      the experimental evidence indicating a link between vestibular compensation and
      the body's response to stress, via the HPA axis.

PMID- 14710902
TI  - Endolymphatic sac tumor (low-grade papillary adenocarcinoma) of the temporal
      bone.
AB  - The entity which has come to be known as an endolymphatic sac tumor (ELST) has,
      in the past, been known as adenocarcinoma of endolymphatic sac origin, aggressive
      papillary tumor of the temporal bone and Heffner's tumor. ELSTs arise in the
      vicinity of the inner ear and may extend to involve both the posterior fossa as
      well as the middle ear and the external ear canal, which may complicate the
      differential diagnosis ELSTs are typically seen in adults, with only rare
      descriptions in pediatric patients. They may be sporadic tumors or they may arise
      as part of the symptom complex of von Hippel-Lindau disease. Clinical signs at
      presentation range from a mass in the external ear canal to sensorineural
      deafness to cranial nerve palsies. Imaging studies reveal a destructive lesion of
      the petrous bone which is heterogeneous on MR scanning. Light microscopy reveals
      two chief patterns: a follicular pattern, reminiscent of thyroid parenchyma; and
      a papillary/solid pattern. Both patterns are often admixed in the same tumor, and
      the individual tumor cells are cytologically bland. Immunohistochemically, ELSTs
      are typically keratin-, vimentin- and epithelial membrane antigen-positive; they
      are often S-100 protein-positive and neuron-specific enolase-positive as well.
      ELSTs are difficult to extirpate surgically (owing to their locally aggressive
      nature); nevertheless, surgical excision remains the mainstay of current therapy.
      These are slow-growing (albeit locally aggressive) tumors which have only rarely
      been reported to metastasize; as such, they remain principally a problem of local
      control.

PMID- 14710903
TI  - Expression of G-protein alpha subunit genes in the vestibular periphery of Rattus
      norvegicus and their chromosomal mapping.
AB  - OBJECTIVE: Heterotrimeric G-proteins play an important role in mediating signals
      transduced across the cell membrane by membrane-bound receptors. The precise role
      of G-proteins and their coupled receptors in the physiology of the vestibular
      neuroepithelium is not well understood. The purpose of this study was to better
      define the role of these proteins by examining their expression in the rat
      vestibular periphery and characterizing their chromosomal location. MATERIAL AND
      METHODS: To characterize G-protein alpha subunit gene expression in the target
      tissue of interest, we performed polymerase chain reaction (PCR) using degenerate
      G-protein primers corresponding to conserved regions in the G-protein alpha
      subunit coding sequence on a normalized rat vestibular cDNA library. PCR
      amplicons were cloned and 50 clones were randomly selected and sequenced.
      Radiation hybrid (RH) mapping was used to determine the chromosomal location of G
      alpha(olf) and two previously identified G-protein alpha subunits--G alpha(i2)
      and G alpha(i2(vest))--in the rat genome. RESULTS: The following G-protein alpha
      subunits were identified in the normalized cDNA library: G alpha(olf), G
      alpha(s), G alpha(o) and G alpha(s2). G alpha(olf) maps to chromosome 18 between
      markers D18Mit17b and D18Mgh2. G alpha(i2) maps to chromosome 8 between markers
      D8Rat65 and D8Mgh2. G alpha(i2(vest)) maps to chromosome 1 between markers
      D1Rat132 and D1Rat202. These chromosomal locations in the rat genome are syntenic
      to chromosomal regions in which the homologous G-protein alpha subunit genes have
      been localized in the human and mouse genomes, further validating RH mapping as
      an effective and accurate tool. We were unable to RH map the location of G
      alpha(o) due to its extensive homology with the hamster gene. CONCLUSION: The
      characterization of G-protein alpha subunit gene expression in the vestibular
      periphery and the chromosomal localization of these genes in the rat revealed
      that a diverse group of these second messengers are expressed.

PMID- 14710904
TI  - Otolith dysfunction during vertiginous attacks in Meniere's disease.
AB  - OBJECTIVE: Vertiginous attacks of Meniere's disease (MD) are characterized by
      various types of vertigo, namely rotatory vertigo, dizziness and drop attack.
      When a patient complains of dizziness without spontaneous nystagmus, otolith
      dysfunction cannot be ruled out. The purpose of this study was to evaluate
      otolith dysfunction during vertiginous attacks of MD or delayed endolymphatic
      hydrops. MATERIAL AND METHODS: Vestibular function tests were carried out daily
      for several days in 11 patients (MD, n = 9; delayed endolymphatic hydrops, n = 2)
      during vertiginous attacks. Otolith function was evaluated by means of the static
      torsional position of both eyes [static ocular torsion (OT)] whilst in an upright
      position. We defined otolith dysfunction as an abnormal change (range) in OT
      without spontaneous nystagmus or as an abnormal change in OT without a change in
      spontaneous nystagmus. RESULTS: Four patients had an abnormal change (range) in
      OT without spontaneous nystagmus or an abnormal change in OT without a change in
      spontaneous nystagmus during vertiginous attacks of MD. CONCLUSIONS: Otolith
      dysfunction occurs in patients during vertiginous attacks of MD. In cases of
      ataxia without spontaneous nystagmus, otolith dysfunction most likely causes
      atypical attacks of MD.

PMID- 14710905
TI  - Expression of angiogenic growth factors in acoustic neurinoma.
AB  - OBJECTIVES: Acoustic neurinoma (AN) can grow to a large size, but the growth
      promoting molecular pathways remain unknown. As angiogenesis has been described
      as being activated in many cancers, we undertook this study in order to examine
      the microvascular network of AN and the expression of angiogenic growth factors
      and their cognate receptors in AN. The aim was to draw conclusions regarding the
      underlying mechanisms and potential benefit of a pathway-specific anticancer
      therapy. MATERIAL AND METHODS: Surgical specimens from 34 patients with AN were
      analysed immunohistochemically for the expression of vascular endothelial growth
      factor (VEGF), VEGF-receptor 1 (VEGF-R1), VEGF-receptor 2 (VEGF-R2) and
      transforming growth factor-beta1 (TGF-beta1). The microvessel density (MVD) was
      defined using CD31 staining and macrophage infiltration using CD68 staining. MVD
      was correlated to tumour size, patient age and duration of symptoms. RESULTS:
      With 1 exception each for VEGF and VEGF-R1, none of the 34 tumours expressed
      either VEGF, TGF-beta1, VEGF-R1 or -R2. No tumour-infiltrating macrophages were
      detected. The MVDs determined were low and did not correlate with tumour size,
      duration of symptoms or patient age. CONCLUSION: These findings indicate that ANs
      either do not express or express very low levels of the analysed proangiogenic
      growth factors. We conclude that tumour angiogenesis is not likely to be a
      relevant mechanism of AN growth and might therefore not be a suitable anticancer
      therapy target.

PMID- 14710906
TI  - Acquisition profiles of syllable-initial consonants in Mandarin-speaking children
      with cochlear implants.
AB  - OBJECTIVES: To examine the production and discrimination skills of Mandarin
      initial-consonant syllables in children with cochlear implants (CIs), as a
      function of both age at implantation and length of CI experience. In addition, we
      also aimed to evaluate the relationship between these children's perception and
      production profiles. MATERIAL AND METHODS: Thirty prelingually deaf children aged
      between 6 years 0 months and 12 years 6 months who received their implants
      between the ages of 2 years 3 months and 10 years 3 months participated. The
      ability of the children to produce the 21 Mandarin initial-consonant syllables
      were elicited using a set of 105 pictures. In addition, the 21 consonants were
      arranged into 16 minimal pairs to determine the children's discrimination skills
      by asking them to accurately identify the target consonants. RESULTS: The
      children's mean accurate consonant production score was 57.9% (SD 19.5%) and the
      average correct consonant discrimination score was 76.67% (SD 11.18%), which was
      significantly higher than the 50% chance level [t(29) = 13.07: p < 0.001]. There
      were significant negative correlations between the performance level of consonant
      production and both age at implantation and length of CI experience. Children who
      received their implants at a younger age (< 6 years) tended to demonstrate an
      acquisition profile similar to that of children with normal hearing, i.e. the
      production and perception skills tended toward near-synchronization, and the
      mastery of production slightly preceded that of perception. CONCLUSION: This
      report demonstrates that early implantation is associated with a near-synchronous
      acquisition profile of the production and discrimination of Mandarin consonants,
      which is similar to that of normal-hearing children at a younger age.
      Specifically, early implantation can promote children's production skills of
      Mandarin initial-consonant syllables.

PMID- 14710907
TI  - Contribution of the vestibular apparatus to postural control when rising from a
      chair.
AB  - OBJECTIVE: The everyday act of rising from a chair is known to require the
      combined angular control of a number of the body's joints, especially those
      within the pitch plane. Precisely how this control is exerted, however, remains
      controversial. The aim of this study was to obtain a better understanding of the
      contribution made by the vestibular apparatus to postural control of the body and
      head when an individual rises from a chair. MATERIAL AND METHODS: A total of 24
      healthy controls and 38 patients with varying degrees of vestibular dysfunction
      were examined. Electromagnetic motion sensors were used to analyze the angular
      control of the head and body as subjects rose from a chair with their eyes open
      or closed. RESULTS: We found that unilateral vestibular dysfunction caused
      fixation of the head with respect to the body, resulting in a loss of spatial
      stability of the head which was not compensated for by visual input. Visual input
      did appear to compensate for bilateral vestibular loss, enabling patients with
      bilateral vestibular apparatus impairment or central disorders to fix the
      position of their head in space. CONCLUSION: The act of rising from a chair is
      normally controlled by vestibular and proprioceptive input; the head is aligned
      according to the gravitational reference so as to obtain stable visual
      information. In patients with unilateral vestibular hypofunction, posture is
      still controlled by these two inputs, although the ability to align the head is
      diminished. In patients with bilateral vestibular hypofunction or a central
      disorder, head alignment is maintained using visual input, although it may not be
      the sole or predominant stabilizing force.

PMID- 14710908
TI  - Effect of botulinum toxin type A on nasal symptoms in patients with allergic
      rhinitis: a double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To investigate the possible beneficial effects of botulinum toxin type
      A (BTX-A) on nasal symptoms in patients with allergic rhinitis (AR). MATERIAL AND
      METHODS: Thirty-four patients (21 females, 13 males; mean age 28 years) were
      included in the study. AR was diagnosed by means of history, clinical examination
      and skin prick test. Patients were randomly divided into 3 subgroups a follows:
      in Group A, 20 units of BTX-A was injected into each nasal cavity (total 40
      units); in Group B, 30 units of BTX-A was injected into each nasal cavity (total
      60 units); and in Group C, 2 ml of isotonic saline was injected as placebo. The
      symptoms of AR (rhinorrhea, nasal obstruction, sneezing, itching) were scored by
      the patient on a six-point scale (from 0 to 5). All of the patients were followed
      up at Weeks 1, 2, 4, 6 and 8; at each visit an anterior rhinoscopic examination
      was done and symptom scores were recorded. RESULTS: There was no statistically
      significant difference between Groups A and B in terms of average symptom scores.
      Rhinorrhea, nasal obstruction and sneezing scores in Groups A and B were
      significantly better than those in Group C at all time points. Although itching
      scores were significantly lower at Weeks 1 and 2, there was no difference in the
      Week 4, 6 and 8 scores in Groups A and B. When total symptom scores were
      evaluated, the results for Groups A and B were similar but significantly better
      than those for Group C. CONCLUSION: In selected cases, injection of 40 units of
      BTX-A into the turbinates, as a single agent, may help the symptomatic control of
      AR for up to 8 weeks.

PMID- 14710909
TI  - Suppressive activity of macrolide antibiotics on nitric oxide production from
      nasal polyp fibroblasts in vitro.
AB  - The influence of macrolide antibiotics on nitric oxide (NO) generation was
      examined using human nasal polyp fibroblasts (NPFs) in vitro. Addition of
      roxithromycin (RXM) at a concentration of > 7.5 microg/ml to cell cultures was
      shown to suppress NO production in response to stimulation with 25.0 ng/ml tumor
      necrosis factor (TNF)-alpha. However, jyosamycin (JM) did not suppress NO
      production from NPFs induced by TNF-alpha stimulation in vitro, even when added
      to cell cultures at a concentration of 20.0 microg/ml. We then examined the
      influence of RXM on inducible nitric oxide synthase (iNOS) mRNA expression in
      NPFs. Addition of RXM at a dose of 7.5 microg/ml to cell cultures caused
      reduction of iNOS mRNA expression, which was enhanced by TNF-alpha stimulation in
      vitro.

PMID- 14710910
TI  - Comparing nasal secretion eosinophil count with skin sensitivity test in allergic
      rhinitis in Ibadan, Nigeria.
AB  - OBJECTIVES: The aim of this prospective study was to assess the usefulness of
      nasal smear eosinophilia compared with a skin sensitivity test for the diagnosis
      of allergic rhinitis and to determine the degree of correlation between the
      tests. MATERIAL AND METHODS: Fifty patients with a clinical history suggestive of
      nasal allergy and 20 controls were studied. A range of allergens were used for
      the skin sensitivity test in both groups. Nasal smears were examined by light
      microscopy. RESULTS: A positive skin test reaction was demonstrated in 90% of the
      study population and 25% of the controls, whereas 76% of the patients and 15% of
      the controls demonstrated significant nasal smear eosinophilia. There was 66%
      correlation between the skin test and nasal eosinophilia, although this was not
      statistically significant (correlation coefficient -0.187 p = 0.193). This study
      does, however, demonstrate that both tests are sensitive for the diagnosis of
      allergic rhinitis, with sensitivities of 0.90 (95% CI 0.82-0.98) for the skin
      test and 0.76 (95% CI 0.64-0.88) for nasal eosinophilia. CONCLUSION: Both the
      skin-prick test and the nasal smear eosinophilia showed correlation with the
      clinical history, although the skin-prick test was more sensitive. No
      statistically significant correlation was demonstrable between the two tests.

PMID- 14710911
TI  - Induction of apoptosis in nasal polyp fibroblasts by glucocorticoids in vitro.
AB  - OBJECTIVE: To examine the possible mechanisms underlying the therapeutic mode of
      action of glucocorticoids (GCs) in nasal polyposis. MATERIAL AND METHODS: The
      effects of GCs on nasal polyps were firstly evaluated by examining the growth of
      fibroblasts derived from 10 nasal polyps in vitro. Subsequently, the ability of
      GCs to induce apoptotic cell death in fibroblasts was examined. RESULTS: Addition
      of betamethasone 21-phosphate (BET) at a concentration of > 1 x 10(-3) M to cell
      cultures inhibited cell growth in all cases examined. BET and dexamethasone 21
      phosphate, but not testosterone or estradiol, caused apoptotic cell death in 2/10
      nasal polyp fibroblasts, as assessed by agarose gel electrophoresis, when the
      cells were cultured with the agents for > 96 h. The minimum concentration of
      agent needed to cause apoptosis was 1 x 10(-3) M, which is half of the
      recommended therapeutic dose. CONCLUSION: The present findings suggest that
      topical application of GCs in nasal polyposis patients suppresses proliferation
      of fibroblasts in polyps and results in favorable modification of the clinical
      status of these patients.

PMID- 14710912
TI  - Uridine-5'-triphosphate and adenosine triphosphate gammaS induce mucin secretion
      via Ca2+-dependent pathways in human nasal epithelial cells.
AB  - OBJECTIVES: Nucleotides such as adenosine triphosphate (ATP) and uridine-5'
      triphosphate (UTP) play fundamental roles in the early stage of secretion in
      nasal epithelial cells via the P2Y receptor. In this study, we examined the
      expression pattern of P2Y subtypes and their functions on Ca2+ influx ([Ca2+]i)
      in normal human nasal epithelial (NHNE) cells. We also examined the effect of UTP
      (an agonist for P2Y2) and ATPgammaS (an agonist for P2Y11) on mucin secretion and
      mucin gene expression. MATERIAL AND METHODS: The expression pattern of P2Y
      receptors and the mRNA levels of MUC5AC, MUC5B and MUC8 were examined after
      treatment with UTP and ATPgammaS by means of reverse transcriptase polymerase
      chain reaction. Mucin was quantified by an immunoblotting assay. We measured
      [Ca2+]i in NHNE cells using a double perfusion chamber. RESULTS: Two uracil
      sensitive receptors (P2Y2, P2Y4) and two adenine-selective receptors (P2Y1,
      P2Y11) were expressed in NHNE cells. UTP and ATPgammaS increased [Ca2+]i via
      caffeine-sensitive pathways, and these two agonists stimulated mucin secretion to
      a similar magnitude without their gene enhancement. In addition, the mucin
      stimulatory effects subsided when the intracellular Ca2+ was removed by 2-bis-(2
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. CONCLUSION:
      This study showed that P2Y2 and P2Y11 receptors were expressed in NHNE cells and
      that their agonists, UTP and ATPgammaS, act as secretogogues on mucin secretion
      via Ca2+-dependent pathways.

PMID- 14710913
TI  - Effects of loratadine on red wine-induced symptoms and signs of rhinitis.
AB  - OBJECTIVE: Intake of red wine may produce nasal symptoms. Little is known about
      the pathophysiology and pharmacology of this condition. The aim of this study was
      to examine whether nasal symptoms produced by red wine are reproducible,
      associated with mucinous secretion or plasma exudation and affected by
      antihistamine treatment. MATERIAL AND METHODS: Twenty-eight subjects with a
      history of nasal symptoms associated with red wine intake received oral
      challenges with red wine and raspberry juice in a crossover design. Nasal
      symptoms and peak inspiratory flow (PIF) were assessed. Nasal lavages were
      performed and levels of fucose and alpha2-macroglobulin were determined as
      indices of mucinous secretion and plasma exudation, respectively. Twelve
      responders (according to preset criteria) were re-challenged 1 h after loratadine
      (10 mg) treatment, in a double-blind, placebo-controlled crossover design. Nasal
      symptoms and PIF were reassessed. Nasal lavages were performed and levels of
      fucose were redetermined. RESULTS: Red wine intake produced nasal symptoms (p <
      0.05) and decreased nasal PIF (p < 0.01-0.05). A total of 54% of subjects were
      categorized as responders, and in this group red wine produced a slight increase
      in lavage fluid levels of fucose (p < 0.05). In contrast, levels of alpha2
      macroglobulin were unaffected. A total of 83% of responders developed symptoms at
      re-challenge. Loratadine reduced post-challenge nasal secretion (p < 0.05). Also,
      red wine failed to reduce nasal PIF in patients receiving loratadine. CONCLUSION:
      Nasal symptoms associated with red wine intake can be reproduced by oral red wine
      challenges. This symptomatology may be associated with mucinous secretion, but
      not with plasma exudation. Loratadine may partially reduce nasal symptoms
      associated with intake of red wine.

PMID- 14710914
TI  - Sleep apnea and Down's syndrome.
AB  - OBJECTIVE: Obstructive sleep apnea has been reported to occur in 20-50% of
      children with Down's syndrome in case series of patients referred for evaluation
      of suspected sleep apnea. In this population-based controlled study, we aimed to
      investigate whether sleep apnea is related to Down's syndrome. MATERIAL AND
      METHODS: Every child aged 2-10 years with Down's syndrome residing in the Umea
      healthcare district (n = 28) was invited to participate in the study, with their
      siblings acting as controls. Successful overnight sleep apnea recordings and
      echocardiography were performed in 17/21 children with Down's syndrome and in 21
      controls. RESULTS: Obstructive sleep apnea could not be diagnosed, either in
      children with Down's syndrome or in the control children. The apnea-hypopnea
      index in the children with Down's syndrome was 1.2 +/- 1.5 and did not differ
      from that in controls. Snoring and hypertrophy of the tonsils were more common in
      children with Down's syndrome than in controls. Children with Down's syndrome
      slept for a shorter time (p < 0.001) and changed body position more often (p <
      0.05) than the control children. CONCLUSIONS: Snoring, restless sleep and
      hypertrophy of the tonsils were common among children with Down's syndrome.
      Obstructive sleep apnea was, however, not related to Down's syndrome in the
      present population-based controlled study.

PMID- 14710915
TI  - Extranodal lymphoma originating from mucosa-associated lymphoid tissue of the
      nasopharynx.
AB  - Non-Hodgkin's lymphoma originating from mucosa-associated lymphoid tissue has
      been connected with autoimmune disease. These tumours often arise in gastric
      mucosa and are extremely rare in airway mucosa. Three cases of mucosa-associated
      lymphoid tissue lymphoma in the cavum have been reported in the literature. A 52
      year-old male with rheumatoid arthritis presented with an 8-month history of
      nasal obstruction and recurrent nasal blood discharge. On physical examination a
      bulky mass was observed in the nasopharynx. CT demonstrated a soft tissue lesion
      in the nasopharynx without bone destruction. MRI showed a contrast-enhanced mass
      with extension to the left pterygoid muscle. Biopsy revealed a low-grade B-cell
      lymphoid tumour of the marginal zone. The patient received six cycles of
      cyclophosphamide, vincristine and prednisone with adriamycin treatment, together
      with intracranial methrotrexate as a prophylactic measure. After 48 months of
      follow-up there was no evidence of disease and a control MRI scan was normal. The
      prognosis of this type of tumour is unpredictable and there are too few cases to
      enable definitive conclusions to be drawn.

PMID- 14710916
TI  - Videostrobokymographic analysis of benign vocal fold lesions.
AB  - OBJECTIVES: Videostrobokymography (VSK) has recently been introduced. The aim of
      this study was to analyze vibratory patterns and objective parameters in various
      benign vocal fold lesions using VSK and to examine the efficacy of VSK in
      clinical applications. MATERIAL AND METHODS: Using VSK, we analyzed the vibration
      patterns of normal vocal folds, various benign lesions such as nodules, polyps,
      cysts and Reinke's edema and cases of unilateral vocal fold paralysis. We also
      calculated the objective parameters open quotient and asymmetric index and
      compared them with their mean values in normal controls. RESULTS: In nodules,
      polyps and cysts, the open quotient at the site of the lesion was similar to the
      mean value in the normal controls; however, on the other parts of the vocal
      folds, it was much larger than the normal mean value. In Reinke's edema,
      irregular and asymmetric vibrations were observed. The posterior area of the
      vocal folds showed larger open quotients than the anterior area. In unilateral
      vocal fold paralysis, irregular vocal fold vibration and incomplete closure of
      the vocal folds were documented. Much larger asymmetric indices were calculated
      for unilateral vocal fold paralysis than in normal controls or for other lesions.
      The asymmetric index may be a good quantitative parameter of vibration in
      patients with vocal fold paralysis. CONCLUSION: This study demonstrated that VSK
      could generate clear quantitative documentation of fine vibrations of vocal folds
      in many different types of benign lesion. VSK has the potential to be an
      effective tool for the quantitative analysis of vibratory patterns of vocal folds
      in clinical settings.

PMID- 14710917
TI  - Skin and eye: uncommon sites of distant metastasis from tongue base squamous cell
      carcinoma.
AB  - The frequency of non-lymphatic distant metastases from primary head and neck
      squamous cell carcinoma (SCC) appears to be higher than previously presumed. The
      general conditions of the affected patients, who usually also present with
      locoregional recurrences, are so impaired as to limit the use of available
      methods for diagnosing the distant spread of head and neck SCC. The incidence
      reported in autopsy studies is approximately three to four times higher than that
      in clinical studies. Lung metastases from head and neck SCC are most common,
      followed by metastases to bone and liver. Metastases to the skin are unusual.
      Secondary ocular localizations of head and neck SCC are exceedingly rare. We
      report the first case of synchronous intraocular (involving the choroid and
      vitreous body) and cutaneous metastases from a recurrent tongue base SCC in a 64
      year-old woman who had undergone radiotherapy, bilateral neck dissection and
      chemotherapy. Cytological evaluation of vitreous aspirate and histological
      diagnosis of the skin lesion were performed < 1 month before the patient's death.
      Skin metastases occur in 1-4% of patients with diagnosed head and neck SCC and
      are usually associated with advanced or recurrent disease. To the best of our
      knowledge, fewer than 10 cases of ocular metastases from head and neck SCC have
      been reported. The average survival time after diagnosis of ocular or skin
      metastases from head and neck SCC is 7 months. Treatment for eye and skin
      metastases is palliative and rarely alters patient outcome.

PMID- 14710918
TI  - Re: Autoimmunity in sudden sensorineural hearing loss...by Cadoni et al.

PMID- 14710919
TI  - It's a bug's life: biosensors for environmental monitoring.

PMID- 14710920
TI  - Development of a framework for metals risk assessment.

PMID- 14710921
TI  - Experimental approaches for size-based metal speciation in rivers.
AB  - A review of the different methodologies employed to fractionate and characterize
      riverine suspended particulate matter is presented. The importance of size-based
      metal speciation is underlined and the possibility of studying it by the
      Sedimentation Field Flow Fractionation (SdFFF) technique is illustrated. The
      studies on the metal load in river Suspended Particulate Matter (SPM) performed
      over the last ten years are critically reviewed focusing on the different methods
      employed to collect, concentrate and size-fractionate samples. The fact that
      there is no homogeneity in methods and data collection in this field is
      underlined. Among the different fractionation techniques, Field Flow
      Fractionation (FFF) methodologies have proved to be a good approach to study the
      role of SPM in metal load and transport. The possibility of studying size-based
      metal speciation using the SdFFF technique is presented and the importance of
      metal speciation in rivers is underlined.

PMID- 14710922
TI  - The use of sensor arrays for environmental monitoring: interests and limitations.
AB  - Continuous, in situ monitoring of air, water and land quality is fundamental to
      most environmental applications. Low cost and non-invasive chemical sensor arrays
      provide a suitable technique for in situ monitoring. Their ability and
      performance under realistic conditions is discussed in this paper. Published
      studies report promising results despite a number of limitations that are
      associated with both the technology itself and its application in ever changing
      ambient conditions. Early investigations include the analysis of single
      substances as well as odour and wastewater organic load monitoring. Reported
      applications typically highlight the sensitivity of the currently available
      sensors to changes in temperature, humidity and flow rate. Two types of
      approaches are recommended to deal with these effects: either working under fixed
      experimental conditions or measuring the external parameters to numerically
      compensate for their change. The main challenge associated with the use of non
      specific sensor arrays lies in establishing a relationship between the measured
      multivariate signals and the standards metrics that are traditionally used for
      quality assessment of gas mixtures. For instance, odour monitoring requires
      calibration against olfactometric measurements while investigations of wastewater
      samples still need to be correlated with organic pollution parameters such as
      BOD, COD or TOC. On the other hand, results obtained in the field have
      demonstrated how sensor arrays can be readily used as simple alarm devices or as
      early warning systems based on a general air/water quality index.

PMID- 14710923
TI  - Water quality test based on dielectrophoretic measurements of fresh water algae
      Selenastrum capricornutum.
AB  - A method is described whereby dielectrophoresis of algal cells is used to perform
      rapid water quality analysis, specifically detecting the presence of CuSO4. The
      dielectric collection spectrum of the fresh water alga Selenastrum capricornutum
      was determined for a range of concentrations of CuSO4 from 25 mg L(-1) to 0.25 mg
      L(-1) for exposure times of 15 min and 18 h. In all cases increasing the
      concentration of CuSO4 reduced cell collection, but a step reduction was observed
      in collection between 2 mg L(-1) and 5 mg L(-1). This method has potential for
      forming a rapid, low-cost test for water quality with broad specificity and
      significantly reduced analysis time compared to current methods.

PMID- 14710924
TI  - Multiplex-PCR and PCR-RFLP assays to monitor water quality against pathogenic
      bacteria.
AB  - In this work we developed and optimized two molecular-based approaches to monitor
      rapidly, sensitively and specifically bacterial pathogens from three different
      genera, Escherichia coli, Pseudomonas aeruginosa, and Salmonella spp., directly
      in waters. To achieve this aim, firstly a multiplex-PCR assay (M-PCR) was
      optimized using a primer pair specific for each pathogen. Secondly, as a
      molecular confirmatory test after isolation of the pathogens by classical
      microbiological methods, PCR-RFLP of their amplified 16S rDNA genes was
      performed. It was observed from the results that the developed M-PCR assay has
      significant impact on the ability to detect sensitively, rapidly and specifically
      the three pathogens directly in water within a short time (5 h from sampling to
      obtain final results), therefore it represents a considerable advancement over
      other known more time-consuming and less-sensitive methods for identification and
      characterization of these kinds of pathogens.

PMID- 14710925
TI  - Application and validation of a new biotic index using data from several water
      systems.
AB  - Protozoans of Lake Donghu were collected from five stations using the PFU method.
      The sampling was conducted for one year and two times a month. The aim of this
      research was to test the applicability of a new protozoa biotic index, species
      pollution value (SPV) and community pollution value (CPV), established by the
      authors using data from the River Hanjiang. Each station's CPV was calculated
      from the SPV and the correlation analysis between the CPV and the comprehensive
      chemical index of stations I, II, III showed a significant correlation between
      them. The pollution status of the five stations was correctly evaluated by the
      CPV. These results suggested that the biotic index could be applied in water
      systems other than the River Hanjiang. The SPV of some protozoa species in Lake
      Donghu, not observed in the River Hanjiang were established. In order to further
      test the applicability of the biotic index, protozoan and chemistry data from the
      Rivers Torrente Stirone and Parma of Italy were used. The results showed that the
      CPV for the two rivers had a close relationship with the chemical water quality,
      which indicated that the biotic index could be applied in other parts of the
      world for the monitoring and estimating of water quality. Since the results of
      testing and verifying the biotic index in some other water systems in China were
      also satisfactory, this indicated that the biotic index has an extensive
      suitability for freshwater ecosystems. As long as more than 50% of the species in
      a sample have a SPV, the CPV calculated from the SPV is reliable for monitoring
      and evaluating water quality.

PMID- 14710926
TI  - Determination of VOCs in yellow eel from various inland water bodies in Flanders
      (Belgium).
AB  - Twenty freshwater eels caught in Flanders (Belgium) were analysed by GC-MS for a
      total of 52 VOCs. The most prominent VOCs are the BTEX and a number of
      chlorinated compounds such as chloroform and tetrachloroethene. The observed
      concentrations which, typically, were in the low ng/g wet weight range, could be
      linked to the major emission sources and the present study gives new evidence
      that combustion of fossil fuels is a major source of BTEX in the environment. The
      concentration levels in eels seem to be a reflection of the actual concentrations
      in their environment. For eels from the same location similar patterns and
      concentrations were observed, and the concentrations agree with what can be
      expected from those of the water column. Generally speaking, the observed
      concentrations do not seem to pose a threat for organisms. More definite
      statements will, however, require a larger dataset. The study suggests that the
      yellow eel can possibly be used as a biomonitor or sentinel organism for VOCs.

PMID- 14710927
TI  - Survey of the occurrence of residues of methyl tertiary butyl ether (MTBE) in
      Dutch drinking water sources and drinking water.
AB  - An indicative survey has been carried out in The Netherlands investigating the
      presence of methyl tertiary butyl ether (MTBE) in drinking water and the
      corresponding sources. In total, 71 different sites used for the preparation of
      drinking water in The Netherlands were sampled in two successive seasons in 2001
      involving the analysis of 156 samples. (ground water (n = 88), surface water (n =
      17), bank filtrate water (n = 6) and drinking water (n = 45)). To combine high
      sample throughput with high selectivity and sensitivity, off-line purge and trap
      for sampling and gas chromatography mass spectrometry equipped with an automated
      thermal desorption sampler (TDS-GC-MS) was selected as the preferred analytical
      methodology. The developed procedure enabled the analysis of at least 40 samples
      per day and provided a limit of quantification of 2 ng l(-1). In the first period
      63 samples of raw water were analyzed. Concentrations ranged between < 10 ng l(
      1) and 420 ng l(-1) with a median concentration below 10 ng l(-1). The second
      period was focused at the re-sampling of positive locations (MTBE > 10 ng l(-1))
      and a few additional drinking water utilities of which both the raw and drinking
      water of the utilities were analyzed. The median concentration of MTBE in the
      selected set of drinking water samples was 20 ng l(-1) (n = 45). At one location
      MTBE was found at a level of 2900 ng l(-1) caused by point source contamination
      of the ground water (11 900 ng l(-1)). Special attention has been paid to the
      quality of the results by analyzing all samples in duplicate and the analysis of
      control samples during each series of analyses.

PMID- 14710928
TI  - Transportation and fate of cationic surfactant in river water.
AB  - The degradation, sorption, transportation and material balance of cationic
      surfactants discharged from domestic waste into river water was studied. Ion-pair
      solid-phase extraction behavior showed that the sorption of cationic surfactants
      as an ion-pair with anionic surfactant onto river sediment was so strong that
      little cationic surfactant was found in the bulk water. Cationic surfactant was
      found in river sediment at more than 500 times higher concentration than that in
      the bulk water. The degradation of the cationic surfactant was very slow in river
      water and much slower in the sediment. A material balance of cationic surfactant
      was estimated for a river running through Toyama City by measuring the flow rate
      and the concentration of cationic surfactant in the water at several points. It
      was found that more than 30% of cationic surfactant introduced to the river was
      lost during the river running through ca. 3 km in 3 h. This reduction probably
      comes from a quick transfer of the cationic surfactant from river water to
      sediment and water weed by means of adsorption or precipitation with suspending
      solids.

PMID- 14710929
TI  - The use of isotopes to identify landfill gas effects on groundwater.
AB  - An evaluation of the source of volatile organic compounds in groundwater samples
      was performed at a landfill in southern California. The 3H (tritium) content of
      the water in leachate and water from the gas-collection system (condensed water
      and entrained water droplets) and the delta 13C and 14C content of the inorganic
      carbon in landfill gas CO2, leachate, and gas-collection system water were used
      to characterize the dissolved inorganic carbon (DIC) inside the landfill, while
      the same parameters were monitored in groundwater samples from affected
      monitoring wells and an unaffected well. Tritium levels from leachate and gas
      collection system condensate ranged from approximately 2000 TU to over 4000 TU,
      orders of magnitude higher than unaffected groundwater. The average 14C content
      of DIC in the landfill pore-water samples was 121 pMC and the 14C content of
      unaffected groundwater DIC was 93 pMC, while the 14C content of the dissolved
      inorganic carbon in groundwater with VOC detections ranged from 105 to 119 pMC.
      The delta 13C of DIC in pore water was consistently above 0 per thousand and the
      delta 13C of unaffected groundwater DIC was -20.3 per thousand, while the delta
      13C of DIC in affected groundwater samples was increased from -17.3 to -13.2 per
      thousand. The increases in both delta 13C and 14C in landfill gas-impacted
      groundwater DIC generally correlated with the number of volatile organic
      compounds detected and their concentrations. Based on the tritium and DIC 14C
      levels in leachate and water from the gas-collection system compared to those of
      unaffected water, significant increases in the tritium content of the water would
      be expected to accompany VOC detections and increases in delta 13C and 14C caused
      by landfill water. The results rule out landfill water as the VOC source, leaving
      landfill gas as the source. The identities and concentrations of the specific
      VOCs in affected groundwater samples varied among wells as well as between two
      leachate samples, ruling out the use of a VOC "fingerprint" for leachate or
      landfill gas to be compared to groundwater VOC concentrations.

PMID- 14710930
TI  - Aluminium speciation in effluents and receiving waters.
AB  - The respective speciation of aluminium in sewage effluent and in river water
      receiving effluent, has been examined. Results showed that concentrations of
      reactive aluminium changed over a timescale of hours and were controlled
      predominantly by pH. A minimum concentration of reactive aluminium occurred at a
      pH of approximately 6.8, coinciding with the prevalence of non-reactive,
      insoluble Al(OH)3 species. For receiving waters of low pH value, typically < pH
      5, a large proportion of the 'naturally present' aluminium can be present in a
      reactive form at concentrations higher than the proposed Environmental Quality
      Standard (EQS). Mixing of waters of this type with effluent of a higher pH value
      leads to the precipitation of aluminium hydroxide. Mixing of effluent of pH value
      in the range 7.5-8.0 with river water in the same (or slightly higher) pH range
      appears to result in no appreciable change in the proportion of reactive
      aluminium; the change in concentration tends to be related simply to dilution. On
      the basis of a theoretical knowledge of aluminium speciation, results obtained in
      this work indicate that it is possible to make predictions about the proportion
      of reactive aluminium present in a receiving water, based on the pH values of the
      effluent water mixture and the concentration in the effluent. Reasonable
      comparisons between measured and predicted values were obtained at higher pH
      values, but the relationship was less certain at pH values less than 6.5 for
      which levels of reactive metal tended to be higher than the quality standard
      value.

PMID- 14710931
TI  - Inventory compilation and distribution of heavy metals in wastewater from small
      scale industrial areas of Delhi, India.
AB  - Delhi has the highest cluster of small-scale industries (SSI) in India. There are
      generally less stringent rules for the treatment of waste in SSI due to less
      waste generation within each individual industry. This results in SSI disposing
      of their wastewater untreated into drains and subsequently into the river Yamuna,
      which is a major source of potable water in Delhi, thus posing a potential health
      and environmental risk to the people living in Delhi and downstream. To study the
      quantity, quality and distribution of heavy metals in liquid waste from
      industrial areas, wastewater, suspended materials and bed sediments were
      collected from industrial areas and from the river Yamuna in Delhi. This study
      has also focused on the efficiency of production processes in small-scale
      industries in India. Heavy metals such as Fe, Mn, Cu, Zn, Ni, Cr, Cd, Co and Pb
      were detected using a GBC 902 atomic absorption spectrometer. The concentration
      of heavy metals observed was as follows: Fe 2-212, Mn 0.3-39, Cu 0.2-20, Zn 0.2
      5, Ni 0.6-6, Cr 0.2-53, Cd 0.08-0.2, Co 0.013-0.55, Pb 0.3-0.7 mg L(-1) in
      wastewater; Fe 5842-78 000, Mn 585-10 889, Cu 206-7201, Zn 406-9000, Ni 22-3621,
      Cr 178-10 533, Co 17-114, Cd 13-141, Pb 67-50 171 mg kg(-1) in suspended
      material; and Fe 3000-84000, Mn 479-1230, Cu 378-8127, Zn 647-4010, Ni 164-1582,
      Cr 139-3281, Co 20-54, Cd 37-65, Pb 228-293 mg kg(-1) in bed residues. This
      indicates that SSI could be one of the point sources of metals pollution in the
      river system.

PMID- 14710932
TI  - Preservation of sulfidic waters containing dissolved As(III).
AB  - Solutions containing variable concentrations of sulfide (0 to 31 ppm) and
      arsenite (0.35 to 10 ppm) were subjected to several different preservation
      treatments. As predicted by equilibrium thermodynamics, at near-neutral pH the
      experimental solutions were undersaturated with respect to orpiment (As2S3).
      However, upon acidification to pH 2 with HCl or HNO3, instantaneous precipitation
      of poorly crystalline As2S3 occurred in sulfidic solutions which resulted in the
      loss of dissolved arsenite. These results have implications concerning the
      practice of acidifying water samples containing hydrogen sulfide with HCl or HNO3
      for the purpose of preserving total arsenic values. If a near-neutral water
      sample contains 1 ppm arsenite and as little as 0.4 ppm sulfide, loss of
      dissolved arsenic will occur upon acidification. An alternative three-step
      preservation method involving base addition, oxidation, and acidification is
      proposed and investigated as an appropriate technique for preserving sulfide
      bearing aqueous samples for total arsenic.

PMID- 14710933
TI  - Analysis of uranium and its correlation with some physico-chemical properties of
      drinking water samples from Amritsar, Punjab.
AB  - Fission track technique has been used for uranium estimation in drinking water
      samples collected from some areas of Amritsar District, Punjab, India. The
      uranium concentration in water samples is found to vary from 3.19 to 45.59 microg
      l(-1). Some of the physico-chemical properties such as pH, conductance and
      hardness and the content of calcium, magnesium, total dissolved solids (TDS),
      sodium, potassium, chloride, nitrate and heavy metals viz. zinc, cadmium, lead
      and copper have been determined in water samples. An attempt has been made to
      correlate uranium concentration with these water quality parameters. A positive
      correlation of conductance, nitrate, chloride, sodium, potassium, magnesium, TDS,
      calcium and hardness with uranium concentration has been observed. However, no
      correlation has been observed between the concentration of uranium and the heavy
      metals analysed.

PMID- 14710934
TI  - Uranium(VL) interactions with OPC/PFA grout.
AB  - The sorption of uranium on to Ordinary Portland Cement (OPC)/Pulverized Fuel Ash
      (PFA, fly ash) grout material has been investigated with respect to time, pH,
      grout:uranium ratio and the chemical composition of the supporting solution. The
      information obtained is of relevance to the disposal of low-level nuclear waste.
      The grout material has been chemically characterised and is negatively charged
      above pH 2.3. At the uranium concentrations studied (2 microM) all uranyl
      hydroxide aqueous species are expected to be monomeric, rather than polymeric.
      Uranium(VI) sorption on to the grout material has been explained in terms of
      inner sphere complexation binding by means of hydroxide bridge formation between
      the uranium and grout surface. It is also proposed that oligomeric uranyl species
      are formed across the grout surface, perhaps stabilising the repulsive effects of
      the negatively charged grout surface and anionic uranyl hydroxide species.
      Thermodynamic modelling has been used to explain the sorption variation versus
      solution pH and identifies potential binding mechanisms.

PMID- 14710935
TI  - The effect of humic acids on the sequential extraction of metals in soils and
      sediments using ICP-AES and chemometric analysis.
AB  - The effect of humic acids on the sequential extraction of metals from various
      soils and sediments has been studied. A new multi-element extraction method
      optimised via experimental design has been employed. The method uses
      centrifugation to pass the extractant solution, at varying pH, through the
      sediment sample. The sequential leaches were collected and analysed by ICP-AES.
      Chemometric data processing was utilised to identify the composition of the
      physico-chemical components in order to characterise the sample. A sediment
      sample collected from Carnon River (Cornwall, UK) and a reference material (NIST
      2711 agricultural soil) were spiked with humic acids and the sequential
      extraction scheme was used to monitor the changes in metal distribution. The
      method has proved a quick and reliable way to evaluate different sediment
      samples, and has potential as a new tool for environmental geochemistry analysis.

PMID- 14710936
TI  - Predominant anthropogenic sources and rates of atmospheric mercury accumulation
      in southern Ontario recorded by peat cores from three bogs: comparison with
      natural "background" values (past 8000 years).
AB  - Peat cores from three bogs in southern Ontario provide a complete, quantitative
      record of net rates of atmospheric Hg accumulation since pre-industrial times.
      For comparison with modern values, a peat core extending back 8000 years was used
      to quantify the natural variations in Hg fluxes for this region, and their
      dependence on climatic change and land use history. The net mercury accumulation
      rates were separated into "natural" and "excess" components by comparing the
      Hg/Br ratios of modern samples with the long-term, pre-anthropogenic average
      Hg/Br. The average background mercury accumulation rate during the pre
      anthropogenic period (from 5700 years BC to 1470 AD) was 1.4 +/- 1.0 microg m(-2)
      per year (n = 197). The beginning of Hg contamination from anthropogenic sources
      dates from AD 1475 at the Luther Bog, corresponding to biomass burning for
      agricultural activities by Native North Americans. During the late 17th and 18th
      centuries, deposition of anthropogenic Hg was at least equal to that of Hg from
      natural sources. Anthropogenic inputs of Hg to the bogs have dominated
      continuously since the beginning of the 19th century. The maximum Hg accumulation
      rates decrease in the order Sifton Bog, in the City of London, Ontario (141
      microg Hg m(-2) per year), Luther Bog in an agricultural region (89 microg Hg m(
      2) per year), and Spruce Bog which is in a comparatively remote, forested region
      (54 microg Hg m(-2) per year). Accurate age dating of recent peat samples using
      the bomb pulse curve of 14C shows that the maximum rate of atmospheric Hg
      accumulation occurred during AD 1956 and 1959 at all sites. In these (modern)
      samples, the Hg concentration profiles resemble those of Pb, an element which is
      known to be immobile in peat bogs. The correlation between these two metals,
      together with sulfur, suggests that the predominant anthropogenic source of Hg
      (and Pb) was coal burning. While Hg accumulation rates have gone into strong
      decline since the late 1950's, Hg deposition rates today still exceed the average
      natural background values by 7 to 13 times.

PMID- 14710937
TI  - Assessment of lead, zinc, copper, nickel and chromium in total suspended
      particulate matter from the workplace in Al-Rusayl Industrial Estate, Oman.
AB  - Total suspended particulates (TSP) were collected with a high volume sampler from
      the indoor work environment of 23 industries in Al-Rusayl Industrial Estate in
      Muscat, Oman. The values measured ranged from 39 microg m(-3) to 1033 microg m(
      3). TSP in the ambient air of the area was found to have an average value of 1802
      microg m(-3). TSP were analyzed for Pb, Cu, Ni, Zn and Cr. Compared to other
      metals, Pb emission was high with values ranging from 3 to 15 109 ng m(-3) with
      the mean value being 1 293 ng m(-3); Cu concentration varied from 3 to 2600 ng m(
      3) with a mean value of 131 ng m(-3); Ni concentration ranged from 6 to 46 ng m(
      3) with a mean value of 17 ng m(-3); Cr concentration ranged from 1 to 133 ng m(
      3) with a mean value of 23 ng m(-3) while that of Zn varied from 0.01 to 1 978 ng
      m(-3) with the mean value being 464 ng m(-3). The concentrations of Pb, Ni, Cu,
      Cr, and Zn in the ambient air were also measured and found to have the following
      values: 122, 18, 16, 5 and 0.01 ng m(-3), respectively. These values indicate
      that the industries in the area do not contribute significantly to heavy metal
      air pollution.

PMID- 14710938
TI  - Seasonal variability of endotoxin in ambient fine particulate matter.
AB  - Endotoxin is a toxic, pro-inflammatory compound that has been detected in indoor
      air and dust in homes and occupational settings, and also in outdoor air. Data on
      the outdoor sampling of endotoxin are limited. Currently, little is known about
      the seasonal variation and influence of temperature on outdoor endotoxin levels.
      In the present study, we report endotoxin levels in fine fraction particulate
      matter with a 50% aerodynamic cutoff diameter of 2.5 microm (PM2.5) and describe
      the seasonal variation of endotoxin in Munich, Germany. In 1999-2000, PM2.5 was
      collected at forty outdoor monitoring sites across Munich. Approximately four
      samples were collected at each site for a total of 158 samples. Endotoxin
      concentrations in the PM2.5 samples were determined using the kinetic chromogenic
      Limulus Amebocyte Lysate (LAL) assay. The geometric mean endotoxin concentration
      was 1.07 EU mg PM2.5(-1) (95% C.I.: 0.915-1.251) or 0.015 EU m(-3) of sampled air
      (95% C.I.: 0.013-0.018). Munich endotoxin levels were significantly related to
      ambient temperature (p < 0.0001) and percent relative humidity (p < 0.0001).
      Sampling periods with higher average temperatures yielded higher levels of
      endotoxin in PM2.5 (r = 0.641), whereas decreases in percent relative humidity
      were associated with increased endotoxin levels in PM2.5 (r = -0.388). Endotoxin
      levels were significantly higher during the warmer seasons of spring [means ratio
      (MR): 2.5-2.7] and summer (MR: 2.1-3.0) than during winter. Although temperature
      and relative humidity do not explain all of the variability in endotoxin levels,
      their effects were significant in our data set. Temperature effects and seasonal
      variation of endotoxin should be considered in future studies of outdoor
      endotoxin.

PMID- 14710939
TI  - Airborne rice pollen and pollen allergen in an agricultural field: aerobiological
      and immunochemical evidence.
AB  - Grass pollens are well known among the health hazardous bioaerosols causing
      respiratory allergy. Being an important member of the grass family, the rice
      plants contribute a huge pollen load in agricultural fields during flowering.
      This results in a seasonal trigger of hay fever and respiratory allergy in the
      field workers and people living in the vicinity. Studies on the monitoring of
      airborne rice pollen and the intensity of the released allergen in agricultural
      fields are largely lacking. The aims of the present study were: (1) daily and
      hourly monitoring of airborne rice pollen in an agricultural field during the
      flowering period of plants in a winter crop season by using the Burkard 7-Day
      Volumetric Sampler and (2) the measurement of hourly airborne allergen intensity
      in the field in a peak rice pollen period by the double-antibody and
      chemiluminescence techniques to find out its relationship with the airborne rice
      pollen concentration. The monthly average concentration of rice pollen was 95
      pollen m(-3) and the range of daily average pollen concentration was 0 to 386
      pollen m(-3). A bimodal diurnal periodicity showed that the airborne rice pollen
      concentrations remained high at two different times of the day: between 08:00 h
      to 12:00 h and 14:00 h to 16:00 h. Deposition of airborne rice pollen allergen
      showed darker intensities on the immunostained tapes from the Burkard Sampler at
      the same two positions corresponding to higher pollen counts. These observations
      provided direct evidence of the allergenicity of airborne rice pollen in field
      conditions.

PMID- 14710940
TI  - Flux of organic compounds from grass measured by relaxed eddy accumulation
      technique.
AB  - Fluxes of some Volatile Organic Compounds (VOC) from grass were measured at a
      golf course in western Sweden, using the Relaxed Eddy Accumulation (REA)
      technique. The sampling was done by collecting VOC onto adsorbent tubes and the
      analysis was performed by thermal desorption followed by GC/MS. High emissions
      were observed after cutting. Transient fluxes of (Z)-3-hexenyl acetate (0.51
      microg m(-2) s(-1)), (Z)-3-hexen-1-ol (0.14 microg m(-2) s(-1)) and (Z)-3-hexenal
      (0.40 microg m(-2) s(-1)) were measured, even at low temperatures. The REA
      technique requires a relatively large fetch area that is sometimes not available.
      Therefore, a procedure for correcting measured fluxes from a limited fetch is
      suggested.

PMID- 14710941
TI  - Atmospheric wet deposition of soluble macro-nutrients in the Cilician Basin,
      north-eastern Mediterranean sea.
AB  - In order to estimate wet deposition atmospheric fluxes of macro-nutrients into
      the eastern Mediterranean coastal waters, soluble inorganic phosphate (PO4(3-)),
      nitrate (NO3-) and nitrite (NO2-) concentrations in precipitation (from February
      1996 to June 1997) have been measured at a coastal sampling site, Erdemli,
      Turkey. Water-soluble inorganic PO4(3)-P, a reactive, bioavailable, limiting
      macro-nutrient in the oligotrophic waters of the eastern Mediterranean was
      studied with respect to its contribution to biological productivity. Reactive
      PO4(3-)-P and NO2(-) + NO3(-)-N concentrations were found to be highly variable
      in rainwater samples. One of the aims of the study was to determine the
      contribution of dust transport to the soluble macro-nutrient budget of the
      eastern Mediterranean. No differences were found between the mean reactive P and
      NO(2-) + NO3(-)-N concentrations of "red rain" and normal rain events. Most
      likely as a result of low solubility of crustal phosphorus, dust episodes were
      not found to be important sources of reactive P, in terms of wet deposition. The
      annual wet deposition fluxes of reactive PO4(3-)-P and NO2(-) + NO3(-)-N into the
      Cilician Basin were respectively estimated to be 0.010 g P m(-2) per year and
      0.23 g N m(-2) per year, which are comparable to the fluxes from land-based
      sources in the north-eastern Mediterranean. The incorporation of water soluble
      bioavailable PO4(3-)-P and NO2(-) + NO3(-)-N delivered via atmospheric wet
      deposition could be responsible for approximately 3.3% (0.40 g C m(-2) per year)
      and 11.0% (1.31 g C m(-2) per year) respectively, of the mean annual new
      production in the north-eastern Mediterranean.

PMID- 14710942
TI  - Airborne observations of vegetation and implications for biogenic emission
      characterization.
AB  - Measuring hydrocarbons from aircraft represents one way to infer biogenic
      emissions at the surface. The focus of this paper is to show that complementary
      remote sensing information can be provided by optical measurements of a
      vegetation index, which is readily measured with high temporal coverage using
      reflectance data. We examine the similarities between the vegetation index and in
      situ measurements of the chemicals isoprene, methacrolein, and alpha-pinene to
      estimate whether the temporal behavior of the in situ measurements of these
      chemicals could be better understood by the addition of the vegetation index.
      Data were compared for flights conducted around Houston in August and September
      2000. The three independent sets of chemical measurements examined correspond
      reasonably well with the vegetation index curves for the majority of flight days.
      While low values of the vegetation index always correspond to low values of the
      in situ chemical measurements, high values of the index correspond to both high
      and low values of the chemical measurements. In this sense it represents an upper
      limit when compared with in situ data (assuming the calibration constant is
      adequately chosen). This result suggests that while the vegetation index cannot
      represent a purely predictive quantity for the in situ measurements, it
      represents a complementary measurement that can be useful in understanding
      comparisons of various in situ observations, particularly when these observations
      occur with relatively low temporal frequency. In situ isoprene measurements and
      the vegetation index were also compared to an isoprene emission inventory to
      provide additional insight on broad issues relating to the use of vegetation
      indices in emission database development.

PMID- 14710943
TI  - Role of volcanic dust in the atmospheric transport and deposition of polycyclic
      aromatic hydrocarbons and mercury.
AB  - The role of volcanic ash as scavenger of atmospheric pollutants, in their
      transport and final deposition to the ground is examined. Attention is focused on
      polycyclic aromatic hydrocarbons (PAHs) and on particulate mercury (Hgp). The ash
      fall deposits studied belong to the 2001 and 2002 eruptive activity of Mount
      Etna, Southern Italy, and were investigated at three (2001) and four (2002) sites
      downwind of the major tephra dispersal pattern. The dry deposition of mercury and
      PAHs was determined, and, in particular, a downward flux to the ground of PAHs
      (approximately 7.29 microg m(-2) per day) and mercury (750 ng m(-2) per day) was
      estimated in Catania from October 26 to October 28, 2002. Finally, evidence on
      the anthropogenic origin of PAHs scavenged from the troposphere by volcanic ash
      is supported by the analysis of PAH compositions in granulometrically homogeneous
      fractions.

PMID- 14710944
TI  - Distribution of polycyclic aromatic hydrocarbons in the atmosphere of Hong Kong.
AB  - This paper reports the monitoring results of eleven polycyclic aromatic
      hydrocarbons (PAHs), four to six-ring, at two urban sites-Central & Western (CW)
      and Tsuen Wan (TW) in Hong Kong from January to December 2000; and the findings
      of a study conducted in 2001 of the partitioning of the gaseous and particulate
      phases of PAHs. The sum of the eleven PAHs under study (sigmaPAHs) was found to
      range from 6.46 to 38.8 ng m(-3). The annual mean levels at 12.2 ng m(-3) and
      15.8 ng m(-3) for CW and TW respectively are comparable to those recorded for the
      previous two years and are also within the reported ranges for other metropolitan
      cities in the Asia Pacific region. Amongst the selected eleven PAHs, fluoranthene
      and pyrene were the two most abundant found in the urban atmosphere of Hong Kong
      during the study period accounting for approximately 80%, of the total PAHs. The
      ratios of benzo(a)pyrene to benzo(g,h,i)perylene (BaP/BghiP) and indeno(1,2,3
      cd)pyrene to benzo(g,h,i)perylene (IDP/BghiP) indicate that diesel and gasoline
      vehicular exhausts were the predominant local emission sources of PAHs. Seasonal
      variations with high winter to summer ratios for each of the individual PAHs (CW:
      1.6-16.7 and TW: 0.82-8.2) and for sigmaPAHs (CW: 1.9 and TW: 1.8) and a spatial
      variation of BaP amongst the air monitoring stations are noted. Results of
      correlation studies illustrate that local meteorological conditions such as
      ambient temperature, solar radiation, wind speed and wind direction have
      significant impact on the concentrations of atmospheric PAHs accounting for the
      observed seasonal variations. A snapshot comparison of the concentrations of PAHs
      at four sites including a roadside site, a rural site and the two regular urban
      sites CW and TW was also performed using the profiles of PAHs recorded on two
      particulate episode days in March 2000.

PMID- 14710945
TI  - Long-term measurement of volatile organic compounds in ambient air by canister
      based one-week sampling method.
AB  - A canister-based 1 week sampling method using a mechanical flow controller and a
      6 L fused-silica-lined canister was evaluated for the long-term measurement of 47
      VOCs in ambient air at pptv (volume/volume) to ppbv levels by use of a three
      stage preconcentation method followed by GC-MS analysis. The GC conditions were
      initially optimized for complete separations of several pptv-level VOCs (e.g.
      vinyl chloride, 1,3-butadiene, acrylonitrile, 1,2-dichloroethane and chloroform)
      in ambient air because the selected ions are easily interfered with by coexisting
      C4-, C5-hydrocarbons and analytes presented at ppbv levels. Thirty-four VOCs
      determined by the 1 week and 24 h sampling method in December 16-22 (2002) had
      concentrations of 6.0-15000 pptv per compound. Concentrations of 28 VOCs
      (including polar VOCs (e.g. methyl isobutyl ketone and butyl acetate)) obtained
      by the method were approximately equal to the mean values calculated from 24 h
      sampling (< +/- 10% deviation). Six VOCs that had low concentrations of 6.0-43
      pptv showed more than +/- 10% deviation. Thirteen VOCs were not detected during
      the entire sampling period. The effect of relative humidity or ozone for the
      specific VOCs (e.g. MIBK, butyl acetate, vinyl chloride, 1,3-butadiene and
      styrene) was negligible.

PMID- 14710946
TI  - Microenvironmental regulation of the initiated cell.
AB  - In the classical skin model of tumor initiation, keratinocytes treated once with
      carcinogen retain their normal appearance and growth behavior indefinitely unless
      promoted to growth into papillomas. Because many of the papillomas regress and
      may recur with further promotion, their cells can also be considered as
      initiated. The growth of initiated keratinocytes can be inhibited either in vitro
      or in vivo by close association with an excess of normal keratinocytes, but it is
      enhanced by dermal fibroblasts. Chick embryo fibroblasts (CEF) in culture produce
      transformed foci after infection with Rous sarcoma virus (RSV) on a background of
      normal CEF in a medium containing 10% or less calf serum (CS), but they retain
      normal appearance and growth regulation in 10% fetal bovine serum (FBS) or 20%
      CS. Transformation of a carcinogen-treated line of mouse embryo fibroblasts is
      prevented, and can be reversed, in high concentrations of FBS in the presence of
      an excess of normal cells. FBS has high, broad-spectrum antiprotease activity.
      Increased protease production occurs in a variety of transformed cells and is
      correlated with progression in tumors. Protease treatment stimulates DNA
      synthesis and mitosis in confluent, contact-inhibited normal cell cultures.
      Synthetic inhibitors of proteases suppress transformation in carcinogen-treated
      cultures and inhibit tumor formation in animals. Several different classes of
      protease may be overexpressed in the same transformed cells. It is proposed that
      excessive protease production accounts for major features of neoplastic
      transformation of initiated cells, but that transformation can be held in check
      by protease inhibitors present in serum and released from surrounding cells. It
      would be informative to determine whether high concentrations of FBS would
      inhibit the neoplastic development of initiated keratinocytes.

PMID- 14710947
TI  - Persistent infection with Helicobacter pylori and the development of gastric
      cancer.
AB  - Gastric malignancies have been closely linked to infection of the gastric mucosa
      with Helicobacter pylori, but the individual factors involved in the multistage
      process of tumor development are still poorly understood. H. pylori evades the
      host defense system and causes persistent infection and chronic inflammation.
      Immune activation leads to DNA damage by the release of oxygen and nitrogen
      radicals. Ongoing tissue repair mechanisms and the secretion of cytokines and
      growth factors, as well as bacterial effector molecules, cause disturbances in
      the balance between epithelial cell proliferation and apoptosis, promote the
      accumulation of potential oncogenic mutations, and support neovascularization and
      tumor growth. In addition, H. pylori might hamper the development of an efficient
      antitumor immunity and provoke immune-mediated pathology. This review summarizes
      the recent progress in the understanding of the intimate bacteria-host
      relationship and the mechanisms by which H. pylori may promote the process of
      tumor development.

PMID- 14710949
TI  - Natural killer cells and cancer.
AB  - Natural killer (NK) cells are lymphocytes that were first identified for their
      ability to kill tumor cells without deliberate immunization or activation.
      Subsequently, they were also found to be able to kill cells that are infected
      with certain viruses and to attack preferentially cells that lack expression of
      major histocompatibility complex (MHC) class I antigens. The recent discovery of
      novel NK receptors and their ligands has uncovered the molecular mechanisms that
      regulate NK activation and function. Several activating NK cell receptors and
      costimulatory molecules have been identified that permit these cells to recognize
      tumors and virus-infected cells. These are modulated by inhibitory receptors that
      sense the levels of MHC class I on prospective target cells to prevent unwanted
      destruction of healthy tissues. In vitro and in vivo, their cytotoxic ability can
      be enhanced by cytokines, such as interleukin (IL)-2, IL-12, IL-15 and interferon
      alpha/beta (IFN-alpha/beta). In animal studies, they have been shown to play a
      critical role in the control of tumor growth and metastasis and to provide innate
      immunity against infection with certain viruses. Following activation, NK cells
      release cytokines and chemokines that induce inflammatory responses; modulate
      monocyte, dendritic cells, and granulocyte growth and differentiation; and
      influence subsequent adaptive immune responses. The underlining mechanism of
      discriminating tumor cells and normal cells by NK cells has provided new insights
      into tumor immunosurveillance and has suggested new strategies for the treatment
      of human cancer.

PMID- 14710948
TI  - High-resolution analysis of genetic events in cancer cells using bacterial
      artificial chromosome arrays and comparative genome hybridization.
AB  - Chromosome analysis of cancer cells has been one of the primary means of
      identifying key genetic events in the development of cancer. The relatively low
      resolution of metaphase chromosomes, however, only allows characterization of
      major genetic events that are defined at the megabase level. The development of
      the human genome-wide bacterial artificial chromosome (BAC) libraries that were
      used as templates for the human genome project made it possible to design
      microarrays containing these BACs that can theoretically span the genome
      uninterrupted. Competitive hybridization to these arrays using tumor and normal
      DNA samples reveals numerical chromosome abnormalities (deletions and
      amplifications) that can be accurately defined depending on the density of the
      arrays. At present, we are using arrays with 6,000 BACs, which provide an average
      resolution of less than 700 kb. Analysis of tumor DNA samples using these arrays
      reveals small deletions and amplifications that were not detectable by chromosome
      analysis and provides a global view of these genetic changes in a single
      hybridization experiment in 24 hours. The extent of the genetic changes can then
      be determined precisely and the gene content of the affected regions established.
      These arrays have widespread application to the analysis of cancer patients and
      their tumors and can detect constitutional abnormalities as well. The
      availability of these high-density arrays now provides the opportunity to
      classify tumors based on their genetic fingerprints, which will assist in
      staging, diagnosis, and even prediction of response to therapy. Importantly,
      subtle genetic changes that occur consistently in tumor cell types may eventually
      be used to stratify patients for clinical trials and to predict their response to
      custom therapies.

PMID- 14710950
TI  - Immunity to cancer through immune recognition of altered self: studies with
      melanoma.
AB  - The adaptive immune system is capable of recognizing cancer through T- and B-cell
      receptors. However, priming adaptive immunity against self antigens is
      potentially a difficult task. Presentation of altered self to the immune system
      is a strategy to elicit immunity against poorly immunogenic antigens. We have
      shown that immunization with conserved paralogues of tumor antigens can induce
      adaptive immunity against self antigens expressed by cancer. Remarkably, cancer
      immunity elicited by closely related paralogues can generate distinct adaptive
      immune responses, either antibody or T-cell dependent. Cancer immunity induced by
      xenogeneic immunization follows multiple and alternative pathways. The effector
      phase of tumor immunity can be mediated by cytotoxic T cells or macrophages and
      perhaps natural killer cells for antibody-dependent immunity. Helper CD4+ T cells
      are typically, but not always, required to generate immunity. Autoimmunity is
      frequently observed following immunization. Cancer immunity and autoimmunity use
      overlapping mechanisms, and therefore they are difficult to uncouple, but
      distinct pathways can be discerned that open the eventual possibility of
      uncoupling tumor immunity from autoimmunity. Studies examining the molecular
      basis for immunogenicity of conserved paralogues are facilitating the development
      of new strategies to rationally design vaccines that trigger adaptive immune
      responses to cancer.

PMID- 14710951
TI  - Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune
      surveillance.
AB  - Interferon-gamma-receptor (IFN-gammaR)-deficient mice are more susceptible to
      tumor induction by methylcholanthrene (MCA) in comparison to control littermates.
      The cellular source of IFNgamma is not known, but the absence of T cells does not
      significantly increase the incidence of MCA-induced tumors. However, it appears
      that the presence of T cells in combination with unknown, perhaps environmental,
      factors can decrease MCA-induced tumor incidence, indicating that IFN-gamma of
      unknown origin contributes to the protective response. The current knowledge of
      cancer biology, immune regulation, and tumor-promoting effects of inflammation
      are difficult to reconcile with the concept of immune surveillance against non
      virus-associated cancer. Analysis of the primary MCA-treated mouse indicates, as
      one protective mechanism, a tissue repair response against MCA-induced damage, in
      the course of which MCA is encapsulated and persists for long time in tumor-free
      mice, termed foreign-body reaction. The protection from DNA damage could
      simultaneously diminish tissue injury and malignant transformation. We argue that
      inhibition of MCA-induced carcinogenesis is mechanistically different from tumor
      transplantation immunity and that a longer latency in MCA-treated mice is
      unlikely due to T cell-mediated tumor recognition and selection of less
      immunogenic variants. We discuss that the IFNgammaR-dependent mechanism against
      MCA is unrelated to the original concept of T cell-mediated immune surveillance
      and that the increased spontaneous tumor incidence observed in some immune
      deficient mice is likely to be explained by opportunistic infection and tumor
      promoting chronic inflammation.

PMID- 14710952
TI  - Epigenetic theories of cancer initiation.
AB  - I argue that carcinogenic insults injure many cells rather than mutate a few.
      This results from evidence that such insults convert too many cells to a
      precancerous state and that too many of the converted cells then revert to
      plausibly involve mutation and its repair; from evidence that the delays between
      such insults and chemically demonstrable mutations are long enough to easily
      allow nonmutational mechanisms to work; from evidence that even ionizing
      radiation first acts on the cytoplasm and mainly affects cells unhit by it; from
      the fact that such insults induce proto-oncogene expression far too quickly to do
      so by mutation; and from the fact that fusions of various cells and cell parts
      show that the tumorous or nontumorous nature of the product depends on its
      cytoplasmic rather than its nuclear component. I further argue that reduced DNA
      methylation, modifications of the histone code, and tissue disorganization are
      the three main mechanisms of epigenetic cancer initiation. Hypomethylation would
      result from DNA excision repair. Moreover, a methyl-deficient diet is
      carcinogenic and demethylation is also known to be carcinogenic via the histone
      code. Finally, I strongly argue for tissue disorganization as a mechanism of
      cancer initiation. This results from evidence that skin carcinogens disrupt the
      dermal/epidermal connection and from the fact that tumorigens swiftly disrupt gap
      junctions, as well as from evidence that such disruption is tumorigenic.

PMID- 14710953
TI  - Contribution of somesthetic cues to the perception of body orientation and
      subjective visual vertical.
AB  - Without relevant visual cues, the subjective visual vertical (SVV) is biased in
      roll-tilted subjects toward the body axis (Aubert or A-effect). This study
      focused on the role of the somatosensory system with respect to the SVV and on
      whether somesthetic cues act through the estimated body tilt. The body cast
      technology was used to obtain a diffuse tactile stimulation. An increased A
      effect was expected because of a greater underestimation of the body position in
      the body cast. Sixteen subjects placed in a tilt chair were rolled sideways from
      0 degrees to 105 degrees. They were asked to verbally indicate their subjective
      body position and then to adjust a luminous line to the vertical under strapped
      and body cast conditions. Results showed a greater A-effect (p < .001) but an
      overestimation of the body orientation (p < .01) in the body cast condition for
      the higher tilt values (beyond 60 degrees). Since the otolith organs produced the
      same gravity response in both conditions, errors were due to a change in
      somesthetic cues. Visual and postural errors were not directly related (no
      correlation). However, the angular distance between the apparent body position
      and the SW remained stable, suggesting that the change in somatosensory pattern
      inputs has a similar impact on the cognitive processes involved in assessing the
      perception of external space and the sense of self-position.

PMID- 14710954
TI  - The integration of auditory and visual motion signals at threshold.
AB  - To interpret our environment, we integrate information from all our senses. For
      moving objects, auditory and visual motion signals are correlated and provide
      information about the speed and the direction of the moving object. We
      investigated at what level the auditory and the visual modalities interact and
      whether the human brain integrates only motion signals that are ecologically
      valid. We found that the sensitivity for identifying motion was improved when
      motion signals were provided in both modalities. This improvement in sensitivity
      can be explained by probability summation. That is, auditory and visual stimuli
      are combined at a decision level, after the stimuli have been processed
      independently in the auditory and the visual pathways. Furthermore, this
      integration is direction blind and is not restricted to ecologically valid motion
      signals.

PMID- 14710955
TI  - Learning in combined-feature search: specificity to orientation.
AB  - We investigated the dynamics and specificity of learning in the search for a
      target defined by combined features belonging to the same dimension (a rotated L)
      among homogeneous or heterogeneous distractors (differently rotated Ls). We found
      that learning makes searching faster although the search strategy does not
      change, remaining parallel with homogeneous distractors and serial with
      heterogeneous distractors. Learning was found to be specific for combined-feature
      orientation, although simple features did not change in the transfer stimulus:
      Transfer was partial when either the target or the distractors were rotated (so
      that their global orientation became the same) and totally absent when target and
      distractors were swapped. These results, which apply to searches among both
      homogeneous and heterogeneous distractors, rule out the possibility that learning
      is specific for orientation of just simple features. Instead, the results suggest
      that specificity of learning with combined features reflects the activation of
      junction detectors responding to a combined feature of a particular orientation.

PMID- 14710956
TI  - Inhibition of return for the length of a line?
AB  - Inhibition of return is most often measured using an exogenous spatial cuing
      method. The experiments presented here follow up on a small number of studies
      that have examined whether a similar effect occurs for nonspatial stimulus
      attributes. In Experiments 1 and 2, the task was to identify a target line as
      either short or long. In this context, targets on valid trials were of the same
      length as that of a preceding cue, whereas targets on invalid trials were of a
      different length than that of a preceding cue. The results were similar to those
      in spatial orienting studies in that responses were slower for valid than for
      invalid targets only at stimulus onset asynchronies (SOAs) longer than 300 msec.
      In Experiment 3, the stimuli were the same but the task was to detect the onset
      of the target line. This task change resulted in slower responses for valid than
      for invalid targets at all SOAs. A similar result was observed in Experiment 4,
      in which validity was defined by color rather than line length, and the task was
      to identify the target color. The discussion centers on an opponent process
      approach to interpreting cuing effects, and consequent difficulties in
      distinguishing spatial and nonspatial cuing effects based on their time course.

PMID- 14710957
TI  - Inhibition of return to occluded objects.
AB  - Since many visual objects are vulnerable to occlusion, an active process that
      tracks objects behind occluders confers considerable ecological validity to the
      visual system. We studied this possibility by testing whether inhibition of
      return can be observed with occluded objects. In our experiments, two moving
      objects disappeared or reappeared behind occluders while a cue and a probe were
      presented. Contrary to the results of a previous study (Tipper, Weaver, Jerreat,
      & Burak, 1994), responses were consistently delayed for the cued object that was
      occluded when it was cued (Experiment 1), when it was probed (Experiment 2), or
      both (Experiment 3). These results suggest that attention can select occluded
      objects that are out of view. Our findings are in line with prior studies that
      have demonstrated similar perceptual/attentional effects for occluded objects, as
      well as for visible objects.

PMID- 14710958
TI  - Prioritizing selection of new elements: bottom-up versus top-down control.
AB  - Watson and Humphreys (1997) have proposed that prioritized selection of new over
      old elements occurs because observers can apply top-down inhibition to the
      locations of the old elements by a mechanism they refer to as visual marking.
      However, recent evidence has suggested that the top-down mechanism is
      questionable (Donk & Theeuwes, 2001). In the present study, we investigated
      whether prioritized selection of new over old elements occurs in a bottom-up or a
      top-down fashion. Observers were presented with displays containing one set of
      elements (old elements) followed, after a certain time interval, by a second set
      of elements (new elements). The observers were instructed to search for the
      presence of a target that was presented with equal probability among the old and
      the new elements (Experiments 1 and 2) or twice as often among the old elements
      than among the new elements (Experiment 3). The results show that new elements
      were prioritized for selection over old ones even though the observers had no
      incentive to do so. The results suggest that prioritized selection of new over
      old elements is not mediated by a top-down inhibition process, as was proposed by
      Watson and Humphreys (1997). Instead, prioritization of new elements appears to
      be a bottom-up process. The implications of these results are discussed in terms
      of models of attentional control.

PMID- 14710959
TI  - Goal-driven modulation of oculomotor capture.
AB  - In a recent study, Ludwig and Gilchrist (2002) showed that stimulus-driven
      oculomotor capture by abrupt onset distractors was modulated by distractor-target
      similarity: Participants were more likely to fixate an irrelevant onset when it
      shared the target color. Here we test whether this pattern of performance is the
      result of (1) inhibition of all items in the distractor color, (2) a response
      bias to local color discontinuities, or (3) the integration of stimulus-driven
      abrupt onset signals with goal-driven information about the target features. The
      results of two experiments clearly support the third explanation. We conclude
      that oculomotor capture is modulated by, but not contingent upon, top-down
      control, and our findings argue for an integrative view of the saccadic system.

PMID- 14710960
TI  - The influence of contrast and spatial factors in the perceived shape of
      boundaries.
AB  - When an edge can be perceived to continue either with a collinear edge of the
      opposite contrast polarity or with a noncollinear edge of the same contrast
      polarity, observers perceive an alignment between the edges of the same contrast
      polarity, even though they are noncollinear. Using several stimulus
      configurations and both free and tachistoscopic viewing, we studied the luminance
      and spatial factors affecting the perceived distortion and binding. The results
      showed that the two noncollinear edges tended to align when they had the same
      contrast polarity (Experiment 1A) and to misalign when they had opposite contrast
      polarity (Experiment 2), providing that (1) they were separated by a distance
      larger than 1 arcmin and smaller than 3-4 arcmin (for all configurations) and (2)
      they laterally overlapped for about 7 arcmin (Experiment 1B). The results also
      showed that the direction of apparent distortion depended on the direction of
      overlapping. The results of Experiment 3 ruled out the local attraction/repulsion
      explanation but, instead, supported the suggestion that the interaction concerned
      the global edges, or part of them, and produced an inward tilt, which made the
      edges of the same contrast polarity perceptually to align, or an outward tilt, so
      that the edges of opposite contrast polarity were perceived to be more
      misaligned. From the overlap and distance limits found, it can be inferred that
      for two noncollinear contours to join perceptually, the tilt must not exceed 18
      degrees, a limit compatible with the orientation bandwidth of contrast-sensitive
      early cortical mechanisms.

PMID- 14710961
TI  - The influence of object-image velocity change on perceived heading in minimal
      environments.
AB  - When human observers move forward and rotate their eyes, a complex pattern of
      light flows across the retina. This pattern is referred to as retinal flow. A
      model has been proposed to explain how humans perceive their direction of self
      movement (or heading) from (1) static depth, (2) direction of image motion, and
      (3) whether image velocity undergoes acceleration or deceleration (Wang &
      Cutting, 1999). However, findings from past research in which sparse or
      minimalist stimuli were used have suggested that not all of the information to
      which participants are sensitive is captured within the scope of this model. In
      particular it has been suggested that the magnitude or size of image velocity
      change may be of significance beyond simply whether image velocity could be
      categorized as speeding up (i.e., accelerating) or slowing down (i.e.,
      decelerating). In two experiments, the influence of this factor on heading
      judgments under minimal conditions was investigated. Evidence was found in
      support of the idea that the rate of image velocity change can influence
      judgments of the direction of self-movement in minimalist conditions.

PMID- 14710962
TI  - Reversible-figure perception: mechanisms of intentional control.
AB  - Observers can exert a degree of intentional control over the perception of
      reversible figures. Also, the portion of the stimulus that is selected for
      primary or enhanced processing (focal-feature processing) influences how
      observers perceive a reversible figure. Two experiments investigated whether
      voluntary control over perception of a Necker cube could be explained in terms of
      intentionally selecting appropriate focal features within the stimulus for
      primary processing. In Experiment 1, varying observers' intentions and the focus
      of primary processing produced additive effects on the percentage of time that
      one alternative was perceived. In Experiment 2, the effect of varying the focus
      of primary processing was eliminated by the use of a small cube, but the effect
      of intention was unaltered. The results indicate that intentional control over
      perception can be exerted independently of focal-feature processing, perhaps by
      top-down activation or priming of perceptual representations. The results also
      reveal the limits of intentional control.

PMID- 14710963
TI  - High familiarity enhances visual change detection for face stimuli.
AB  - Does high familiarity with a face enable particularly efficient visual
      processing? In three experiments, we presented briefly and successively two pairs
      of faces (either famous or recently learned), masking each presentation. Between
      the first and the second presentations, one face changed, and the task was to
      locate this change. Performance was significantly better when the change involved
      a famous face. This superfamiliarity effect was found only for changes occurring
      in the left visual field and was abolished by inverting the faces. Extended prior
      study of the recently learned faces did not improve performance with these
      stimuli. The results suggest that superfamiliarity promotes highly efficient
      visual processing and may especially activate a configural mode of analysis.

PMID- 14710964
TI  - Semantic activation in the absence of perceptual awareness.
AB  - Participants performed a semantic categorization task on a target that was
      preceded by a prime word belonging either to the same category (20% of trials) or
      to a different category (80% of trials). The prime was presented for 33 msec and
      followed either immediately or after a delay by a pattern mask. With the
      immediate mask, reaction times (RTs) were shorter on related than on unrelated
      trials. This facilitatory priming reached significance at prime-target stimulus
      onset asynchronies (SOAs) of 400 msec or less and remained unaffected by task
      practice. With the delayed mask, RTs were longer on related than on unrelated
      trials. This reversed (strategic) semantic priming proved to be significant (1)
      only at a prime-target SOA of 400 msec or longer and (2) after the participants
      had some practice with the task. The present findings provide further evidence
      that perceiving a stimulus with and without phenomenological awareness can lead
      to qualitatively different behavioral consequences.

PMID- 14710965
TI  - Does right-left prevalence occur for the Simon effect?
AB  - In four experiments, we investigated whether a right-left prevalence effect
      occurs for the Simon task, in which stimulus location is irrelevant, when the
      stimulus and the response sets vary along horizontal and vertical dimensions
      simultaneously. Simon effects were evident for both dimensions, and they were of
      similar magnitude, indicating no prevalence effect. Manipulations of the relative
      salience of the dimensions for the stimulus and the response sets resulted in a
      larger Simon effect for the more salient dimension than for the less salient one,
      but there was no overall prevalence effect. The results indicate that
      manipulations of salience affect the relative magnitudes of automatic response
      activation for the vertical and the horizontal dimensions but that the right-left
      prevalence effect is due to a coding bias in intentional response selection
      processes when stimulus location is relevant.

PMID- 14710966
TI  - ARDS: predicting mortality and improving survival.

PMID- 14710967
TI  - Botulinum toxin--role in headache prophylaxis.

PMID- 14710968
TI  - Clinical profile of ARDS.
AB  - OBJECTIVES: Several studies have been published in western literature on
      incidence, prevalence, clinical course, outcome and mortality in patients with
      acute respiratory distress syndrome (ARDS). There are very few studies on the
      pattern of ARDS seen in Indian population. There are anecdotal reports of ARDS
      associated with different tropical diseases and the exact association of these
      life-threatening disorders with ARDS is not clearly described in the Indian
      literature. The study was carried out to identify the clinical pattern of Indian
      patients who died of ARDS. METHODS: This was a three and a half year
      retrospective study comprising of 98 patients who died of ARDS in the intensive
      care unit of Apollo Hospital, a tertiary care referral centre between January
      1999 to June 2002. The present study looked at only those patients who died from
      ARDS and did not evaluate the clinical outcome or survival pattern of ARDS
      patients. The criteria used for diagnosis of ARDS was based upon
      American/European consensus statement for definition of acute lung injury (ALI)
      and ARDS. The patient demographic data consisted of age, sex, associated major
      illness in the part, clinical disorders associated with ARDS, length of hospital
      stay, use and duration of mechanical ventilation and the presence of sepsis and
      organ failure defined by ACCP/SCCM consensus conference definition. Seventy
      patients were ventilated with volume control mode and 28 patients with pressure
      control ventilation. Lung protective strategy was used in all the cases
      comprising of low tidal volumes at the rate of 5-ml/kg-body weight. Statistical
      analysis of the data was done by SPSS 10 for windows (SPSS, Inc., Chicago,
      Illinois). RESULTS: There were 98 patients during the study period who died of
      ARDS. Fifty one males and 47 female patients. Thirty patients had primary
      pulmonary infection, 18 had severe sepsis with multiorgan failure, 12 patients
      had polytrauma and 10 each had recent abdominal surgery and pancreatitis. Length
      of ICU stay was less than 10 days in 58 patients whereas in 40 patients it was
      more than 10 days. Duration of mechanical ventilation was less than seven days in
      80 patients and more than seven days in 18 patients. Positive body fluid cultures
      were obtained in 42 out of 98 patients and of these, 14 patients had
      microbiological diagnosis established by blood culture, another 14 by
      endotracheal secretion culture, eight by urine culture and in the remaining six
      patients based upon wound cultures. The commonest organisms isolated from the
      body fluids were Pseudomonas and Klebsiella. CONCLUSION: Primary pulmonary
      infection was associated with ARDS is one-third of patients. Multiorgan failure
      was seen in 18% of patients who died from ARDS. Severe sepsis was identified as a
      significant risk factor for ARDS.

PMID- 14710969
TI  - Primary Sjogren's syndrome: rarity in India.
AB  - OBJECTIVE: Primary Sjogren's syndrome (SS) is rarely reported from India. We have
      studied the clinical spectrum and immunological profile of patients with primary
      SS. METHODS: A prospective analysis of patients with primary Sjogren's syndrome
      fulfilling San Francisco criteria, seen at our clinic in the last 10 years was
      carried out. RESULTS: The study included 26 patients, 21 being women. The
      presenting symptoms included dry eyes, dry mouth, and arthritis/arthralgia. Extra
      glandular manifestations were glomerulonephritis, vasculitis, renal tubular
      acidosis and peripheral neuropathy. The important laboratory abnormalities were
      hypergammaglobulinaemia (16/20), antinuclear antibodies (18/26), anti-La (11/19)
      and anti-Ro (10/19). Minor salivary gland provided a definitive diagnosis in
      16/26 (60%). CONCLUSION: The prevalence of primary Sjogren's syndrome is rare
      even in tertiary care rheumatology clinics. The clinical and immunological
      profile as seen here is similar to that reported in Western countries.

PMID- 14710970
TI  - The Chennai Urban Rural Epidemiology Study (CURES)--study design and methodology
      (urban component) (CURES-I).
AB  - The report of World Health Organization (WHO) shows that India tops the world
      with the largest number of diabetic subjects. This increase is attributed to the
      rapid epidemiological transition accompanied by urbanization, which is occurring
      in India. There is very little data regarding the influence of affluence on the
      prevalence of diabetes and its complications particularly retinopathy in the
      Indian population. Furthermore, there are very few studies comparing the
      urban/rural prevalence of diabetes and its complications. The Chennai Urban Rural
      Epidemiology Study (CURES) is designed to answer the above questions. CURES is
      initially planned as a cross-sectional study to evolve later into a longitudinal
      study. Subjects for the urban component of the CURES have been recruited from
      within the corporation limits of Chennai City. Chennai (formerly Madras), the
      largest city in Southern India and the fourth largest in India has been divided
      into 10 zones and 155 wards. 46 wards were selected by a systematic random
      sampling method to represent the whole of Chennai. Twenty thousand and one
      individuals were recruited for the study, this number being derived based on a
      sample size calculation. The study has three phases. Phase one is a door to door
      survey which includes a questionnaire, anthropometric, fasting capillary blood
      glucose and blood pressure measurements. Phase two focussed on the prevalence of
      diabetic complications particularly retinopathy using standardized techniques
      like retinal photography etc. Diabetic subjects identified in phase one and age
      and sex matched non-diabetic subjects will participate in these studies. Phase
      three will include more detailed studies like clinical, biochemical and vascular
      studies on a sub-sample of the study subjects selected on a stratified basis from
      phase one. CURES is perhaps one of the largest systematic population based
      studies to be done in India in the field of diabetes and its complications like
      retinopathy, nephropathy and neuropathy.

PMID- 14710971
TI  - Role of multidetector CT virtual bronchoscopy in the evaluation of post
      tracheostomy tracheal stenosis--a preliminary study.
AB  - AIM: To study the technique and utility of virtual bronchoscopy (virtual reality
      endobronchial simulation, VRES) as a tool to evaluate post-tracheostomy tracheal
      stenoses and to correlate the findings of virtual and invasive bronchoscopy and
      to follow-up treated lesions or those currently under treatment that were
      initially diagnosed with VRES. METHODOLOGY: This prospective study comprised nine
      patients in the age group 13 to 65 years presenting with breathlessness and
      stridor following one or multiple tracheostomies. They underwent plain CT using a
      multidetector CT (MDCT) scanner (Siemens Volume Zoom) using narrow (1 mm)
      collimation. These thin slice images were post-processed using an Irix-based
      workstation with a 'Fly-Through' endoscopy application. These patients also
      underwent a rigid (three patients) or fiberoptic (six patients) bronchoscopy.
      RESULTS: Of the nine patients that underwent VRES, five were found to have
      stenoses, three had obstructing granulation tissue, one had an obstructing
      membrane and one had synechiae. The invasive bronchoscopic findings supported the
      VRES diagnosis in all but one case of stenosis, one of granulation tissue and the
      case with synechiae. Membranes and synechiae were relatively difficult to
      diagnose without the corresponding axial and multiplanar images. VRES achieved a
      higher sensitivity, while invasive bronchoscopy a higher specificity.
      CONCLUSIONS: VRES proved to be comparable to invasive bronchoscopy in the
      depiction of post-tracheostomy tracheal stenoses, with a notable advantage in
      critical stenoses in that the airway distal to the stenosis could be assessed
      with VRES but not with invasive bronchoscopy. A preliminary VRES was found to be
      of assistance in the selection of patients for the more invasive therapeutic
      procedures such as laser ablation of granulation tissue and its follow-up.

PMID- 14710972
TI  - A cost-effectiveness analysis of three antimalarial treatments for acute,
      uncomplicated Plasmodium falciparum malaria in Mumbai, India.
AB  - BACKGROUND: Malaria is a major public health problem representing 2.3% of the
      overall global disease burden. The cost of treatment of malaria continues to rise
      as older drugs and insecticides become less effective and are replaced by more
      effective, but also more expensive products. METHODS: A post-hoc pharmacoeconomic
      analysis (direct and indirect costs only) of three antimalarials, chloroquine,
      mefloquine and co-artemether, was carried out to address the problem of switch to
      a more expensive first-line antimalarial in the face of growing chloroquine
      resistance. RESULTS: From the perspective of a large public hospital, it was seen
      that in an area of high grade chloroquine resistance, the total expenditure on
      patients who fail chloroquine would exceed the excess expenditure on mefloquine
      when the RII + RIII resistance exceeded 9%. CONCLUSIONS: Switch to a more
      expensive drug like mefloquine as a first-line option would be cost-effective
      when the moderate-severe chloroquine resistance exceeded 9%.

PMID- 14710973
TI  - Large pericardial effusion: the differentiation of tuberculous from chronic
      idiopathic effusion.
AB  - AIMS: Tuberculosis is a common cause of pericardial effusion in many parts of the
      world often presenting with tamponade. Its recognition is important but not
      always easy. This study was to prospectively compare the features of tuberculous
      with chronic idiopathic pericardial effusion. METHODOLOGY: We studied 47 patients
      with large pericardial effusions or tamponade. All had pericardiocentesis and
      chest CT studies. Twenty-eight had tuberculous and 19 viral or idiopathic
      effusion. Pericardial biopsy was done in 26/28 and tuberculin skin test in 23/28
      with tuberculosis and all received specific treatment. RESULTS: Patients with
      idiopathic effusion were older with thinner pericardium. Tamponade was frequent
      in both groups (64%). Fever (p<0.001) and pericardial rub (p<0.002) were more
      with tuberculosis. The skin test measured 17 +/- 3.2 mm. On echocardiography
      pericardial deposits and strands in the pericardial space were more with
      tuberculosis. The fluid was similar in quantity and quality. Only and all 28 with
      tuberculosis had enlarged mediastinal lymph glands on CT measuring 19.5 +/- 8.3
      mm. On follow up of 16 +/- 10.2 months glands disappeared in 81% and regressed in
      19%. Lymphadenopathy was not seen in any patient with viral/idiopathic
      pericarditis. All patients in both groups were well at follow up. CONCLUSIONS:
      Tamponade is frequent with large tuberculous and chronic idiopathic effusions.
      The quantity and quality of the effusion were similar. Fever and pericardial rub
      were more frequent with tuberculosis as also deposits and strands on
      echocardiography and patients had a strongly positive skin test. Mediastinal
      lymph gland enlargement on chest CT was found only and in all with tuberculous
      effusion.

PMID- 14710974
TI  - Pneumomediastinum and pneumopericardium in staphylococcal bronchopneumonia.

PMID- 14710975
TI  - Pitting oedema in hypothyroidism.

PMID- 14710976
TI  - H.L. Helmholtz (1821-1894) postal stamp released in West Berlin--1971 in Germany-
      1994.

PMID- 14710977
TI  - Adjuvant role of vitamin B analogue (sulbutiamine) with anti-infective treatment
      in infection associated asthenia.
AB  - AIMS OF THE STUDY: Asthenic symptoms such as weakness accompany illness. This
      study investigates whether the centrally acting cholinergic agent, vitamin B
      analogue (sulbutiamine), is effective and acceptable in relieving these symptoms
      in infectious disease when combined with specific anti-infective treatment.
      METHODOLOGY: In a prospective uncontrolled, non-randomised, commercial,
      observational study, 1772 patients with an infectious disease and asthenic
      symptoms, drawn from the practice of 350 randomly selected physicians throughout
      India, received vitamin B analogue (sulbutiamine) in addition to specific anti
      infective treatment for 15 days. The primary outcome variable was complete
      resolution of asthenic symptoms with treatment. RESULTS: The number (%, 95%
      confidence interval) of patients with complete resolution of all asthenic
      symptoms was 916 (51.7, 49.4-54). In the remaining patients, severe asthenia was
      reduced but persisted in 11 (0.6, 0-26); and moderate asthenia in 94 (5.3, 0
      17.6). The response was greater in patients with acute infection and symptoms
      more related to cerebral function. Side effects occurred in 10 (0.6%), patients
      and well being improved significantly. CONCLUSIONS: Vitamin B analogue
      (sulbutiamine) may be a useful adjunct to specific anti-infective treatment.

PMID- 14710978
TI  - Botulinum toxin in migraine.

PMID- 14710979
TI  - Smoking--a renal risk factor.
AB  - Smoking has adverse effects on health, causing ischemic heart disease, stroke,
      chronic obstructive lung disease and cancers of the respiratory,
      gastrointestinal, pancreas, kidney and urinary tract. Smoking causes an acute
      increase in mean arterial pressure and heart rate. Chronic smoking reduces the
      renal plasma flow. There is clinical evidence that smoking has adverse effects on
      renal outcome in essential hypertension, diabetic nephropathy, primary glomerular
      diseases, systemic diseases involving the kidney and renal allograft recipients.

PMID- 14710980
TI  - Echocardiography in evaluation of pericardial disease.

PMID- 14710981
TI  - Brainstem death: implications in India.
AB  - Brainstem death and brain death although practically same with regards to the
      concept of organ donation, remain technically different. Brain death mandates
      irreversible cessation of all the functions of the entire brain and brainstem
      while brainstem death signifies irreversible damage to the brainstem. As per the
      Indian law, brainstem death is the legal requirement and not brain death.

PMID- 14710982
TI  - Pulmonary mucormycosis presenting with recurrent laryngeal nerve palsy.
AB  - Pulmonary mucormycosis is an uncommon infection and its endobronchial form is
      rare. Fever, cough, dyspnoea and hemoptysis are the usual presenting symptoms.
      Hoarseness of voice, a rare manifestation of endobronchial mucormycosis, has been
      reported earlier but its exact anatomical basis was unclear. We report an
      instance of polypoid endobronchial mucormycosis and vocal cord paralysis in a
      patient with type I diabetes and diabetic ketoacidosis.

PMID- 14710983
TI  - Hyperhomocysteinemia masquerading as pulmonary embolism.
AB  - We describe a 30-year-old male who presented with acute onset of breathlessness,
      tachycardia, and palpitations associated with distension of jugular vein and
      clear lungs on physical examination. The chest X-ray was normal and ECG was
      showing S1Q3T3 and right ventricular strain pattern. His 2-D echocardiography was
      showing dilated right atrium, right ventricular dilatation and moderate pulmonary
      arterial hypertension. He was found to have thrombosis involving left side of
      deep venous system with normal superficial venous system (Doppler proved). All
      routine blood investigations for etiology of recurrent DVT were normal except
      serum homocyteine level, which was significantly raised. Megaloblastic anemia on
      peripheral smear and hyperhomocysteinemia prompted us to search for its cause,
      which was subsequently found to be vitamin B12 deficiency. Such an association of
      megaloblastic anemia due to vitamin B12 deficiency leading to
      hyperhomocysteinemia and subsequent thrombosis in left venous system presenting
      as acute pulmonary embolism has not been described earlier in the medical
      literature.

PMID- 14710984
TI  - Prenatal diagnosis in a haemophilia A family by both factor VIII activity and
      antigen measurements.
AB  - With the advent of molecular biology techniques prenatal diagnosis in haemophilia
      A is generally being performed by first trimester chorionic villus sampling
      followed by the DNA analysis using various polymorphic markers of factor VIII
      gene. Here we report antenatal diagnosis in a haemophilia A family performed in
      the second trimester by measuring both factor VIII:C and factor VIII:Ag in the
      fetal blood sample.

PMID- 14710985
TI  - Bilateral renal papillary necrosis due to Candida infection in a diabetic patient
      presenting as anuria.
AB  - A 38 years insulin-dependent diabetic male, with nephropathy on antituberculous
      treatment presented with painless frank hematuria followed by anuria for a day
      which was associated with fever. Ultrasonogram of the abdomen showed bilateral
      hydroureteronephrosis. Necrotic papillae were retrieved after ureteroscopy which
      on histopathological examination and culture showed Candida albicans. This was
      successfully treated with fluconazole and ureteroscopic removal of necrotic
      papillae.

PMID- 14710986
TI  - Spinal neurenteric cyst presenting as burning feet syndrome.
AB  - Spinal neurenteric cysts are rare congenital cysts of endodermal origin. A 34
      years old man presented with burning feet syndrome of two years duration.
      Magnetic resonance imaging (MRI) revealed an intradural extramedullary cystic
      mass lesion extending from L2 to L5 vertebrae causing severe compression and
      displacement of terminal portion of conus medullaris and filum terminale to the
      right side. Additionally, tethered cord and filar lipoma were also present.
      Cystic mass and filar lipoma were resected along with release of tethered cord.
      Histopathology confirmed a neurenteric cyst. This case is reported in view of
      rare occurrence and peculiar presentation.

PMID- 14710987
TI  - Red cell exchange using cell separator (therapeutic erythrocytapheresis) in two
      children with acute severe malaria.
AB  - Red cell exchange using a cell separator (therapeutic erythrocytapheresis) has
      been used successfully in a large number of clinical conditions including acute
      severe cases of malaria. We report two children suffering from severe malaria
      (Plasmodium falciparum) with infestation rates of 75% and 67% respectively. They
      were treated successfully with erythrocytapheresis in combination with
      antimalarial treatment.

PMID- 14710988
TI  - Evaluation of the beta cell response by C-peptide measurement in parents of
      children with type I diabetes.

PMID- 14710989
TI  - Ineffectiveness of iron polymaltose in treatment of iron deficiency anemia.

PMID- 14710991
TI  - Marrow scan in assessment of osteomyelitis in the diabetic foot.

PMID- 14710990
TI  - Time to take leptospirosis seriously in India!

PMID- 14710992
TI  - Is the 'rule of halves' in hypertension still valid? Evidence from the Chennai
      urban population study.

PMID- 14710993
TI  - Respiratory disorders and air travel: role of physician.

PMID- 14710994
TI  - Saving quinolones for tuberculosis.

PMID- 14710995
TI  - Glycoinositolphospholipid from Trypanosoma cruzi: structure, biosynthesis and
      immunobiology.
AB  - The pathogenic protozoan parasite Trypanosoma cruzi expresses on its surface an
      unusual family of glycoinositolphospholipids (GIPLs) closely related to
      glycosylphosphatidylinositol (GPI) anchors. Different parasite isolates express
      distinct GIPLs which fall into two series, depending on the substitution of the
      third mannosyl residue in the conserved glycan sequence Man4-(AEP)-GlcN-InsPO4 by
      ethanolamine phosphate or beta-galactofuranose. Although the exact role of these
      molecules in the cell biology and pathogenicity of T. cruzi remains unknown, the
      lipid and glycan moieties impart distinct responses to host T and B lymphocytes
      and phagocytes, overall favouring an immune response permissive to the parasite.
      The biosynsthesis of GIPLs follows a pathway similar to that observed for GPI
      anchors. However, a more detailed understanding might enable the development of
      specific inhibitors of parasite-specific enzymes and lead to novel drugs to
      ameliorate Chagas disease.

PMID- 14710996
TI  - Biodiversity and evolution of the Myxozoa.
AB  - Myxozoans (phylum Myxozoa) are metazoan parasites utilizing invertebrate and
      (mainly) aquatic vertebrate hosts. They have in common with cnidarians the
      possession of virtually identical, highly complex organelles, namely the polar
      capsules in myxozoan spores, serving for attachment to new hosts and the
      nematocysts in surface epithelia of cnidarians, serving for food capture.
      Although myxozoan spores are multicellular, the simple trophic body forms of
      almost all species, reduced to syncytial plasmodia or single cells, reveal no
      clues to myxozoan ancestry or phylogenetic relationships. The myxozoan genus
      Buddenbrockia is one of only two known genera belonging to a clade which diverged
      early in the evolution of the Myxozoa. Today the Myxozoa are represented by two
      classes, the Myxosporea, containing all the better-known genera, which alternate
      between fish and annelids, and the Malacosporea, containing Buddenbrockia and
      Tetracapsuloides, parasitising bryozoans. The latter genus also infects salmonid
      fish, causing proliferative kidney disease (PKD). The enigmatic Buddenbrockia has
      retained some of its ancestral features in a body wall of two cell layers and a
      worm-like shape, maintained by four longitudinally-running muscle blocks, similar
      to a gutless nematode and suggestive of a bilaterian ancestry. Although some
      analyses of 18S rDNA sequences tend towards a cnidarian (diploblast) affinity for
      myxozoans, the majority of these studies place them within, or sister to, the
      Bilateria. The latter view is supported by their possession of central class Hox
      genes, so far considered to be synapomorphic for Bilateria. The simple body form
      is, therefore, an extreme example of simplification due to parasitism. Various
      hypotheses for the occurrence of identical complex organelles (nematocysts and
      polar capsules) in diploblast and triploblast phyla are evaluated: common
      ancestry, convergent evolution, gene transfer and, especially, endosymbiosis. A
      theory of the evolution of their digenetic life cycles is proposed, with the
      invertebrate as primary host and secondary acquisition of the vertebrate host
      serving for asexual population increase.

PMID- 14710997
TI  - The mitochondrial genomics of parasitic nematodes of socio-economic importance:
      recent progress, and implications for population genetics and systematics.
AB  - Mitochondria are subcellular organelles in which oxidative phosphorylation and
      other important biochemical functions take place within the cell. Within these
      organelles is a genome, called the mitochondrial (mt) genome, which is distinct
      from, but cooperates closely with the nuclear genome of the cell. Investigating
      mt genomes has significant implications for various fundamental research areas,
      including mt biochemistry and physiology, and, importantly, such genomes provide
      a rich source of markers for population genetic and systematic studies. While
      approximately 250 complete mt genome sequences have been determined for a range
      of metazoan organisms from various phyla, few of these represent parasitic
      helminths. Until 1998, only two mt genome sequences had been determined for
      parasitic nematodes, in spite of their socio-economic importance and the need for
      investigations into their population genetics, taxonomy and evolution. However,
      since that time, there has been some progress. The main focus of the present
      chapter is to review the state of knowledge of the mt genomics for parasitic
      nematodes, to describe recent technological improvements to mt genome sequencing,
      to summarize applications of mt gene markers for studying the systematics and
      population genetics of parasitic nematodes, and to emphasize prospects and
      opportunities for future research in these areas.

PMID- 14710998
TI  - The cytoskeleton and motility in apicomplexan invasion.
AB  - We consider the cytoskeletal structure, function, and motility of the invasive
      zoites of the Apicomplexa. This monophyletic group possess a prominent
      microtubular cytoskeleton, with a very distinct polarity. It is associated with a
      non-actin based filamentous system, and with a cisternal double membrane assembly
      beneath the plasma membrane. The origin of the microtubular cytoskeleton is a set
      of apical rings. Its role in motility is still unclear, but the present knowledge
      of apicomplexan tubulins' molecular biology and chemistry is outlined. Actin and
      accessory proteins are present, and it is apparent that actin polymerisation is
      tightly controlled in zoites. It does not contribute to the cytoskeleton
      ordinarily, but is crucial in the acto-myosin linear motor which drives gliding,
      capping, and invasion, the best understood aspects of zoite motility. Several
      myosins distinct from the primary linear motor myosin are also found, but not yet
      well understood functionally. Many of the myosins fall into a class of the
      superfamily so far seen only in this phylum. The possible relationships of the
      actin, myosin, cytoskeletal linkage proteins, and external force-transducing
      adherent proteins are discussed.

PMID- 14710999
TI  - The contribution of Salvador Moncada to our understanding of the biology of
      nitric oxide.
AB  - The observation, by Furchgott and Zawadzki, that a factor of short average life,
      released by endothelial cells accounted for vasodilation was the beginning of one
      of the most fascinating adventures in the recent history of science. The
      discovery that this released factor was nitric oxide had tremendous implications
      for our understanding not only of the homeostasis of the vascular tissue, but
      also of a variety of other biological processes ranging from synaptic plasticity
      to regulation of immune responses. This review article will lead the reader
      through the landmark events in this adventure, highlighting the fundamental role
      played by Salvador Moncada and his team.

PMID- 14711000
TI  - Peroxynitrous acid--where is the hydroxyl radical?
AB  - Peroxynitrite is an inorganic toxin of physiological interest, formed from the
      diffusion-controlled reaction of superoxide and nitrogen monoxide with a rate
      constant of (1.6 +/- 0.3) x 10(10) M(-1) s(-1). On the basis of three experiments
      we conclude that homolysis of the O-O bond in peroxynitrous acid is unlikely: (1)
      the yield of nitrite from the decomposition of peroxynitrite shows a dependence
      on the peroxynitrite concentration and is lower than expected for homolysis; (2)
      the yield of [15N]nitrate from the reaction of [15N]nitrite with peroxynitrous
      acid predicted by homolysis does not correspond to that found experimentally, and
      (3) the reaction of peroxynitrous acid with monohydroascorbate does not yield
      ascorbyl radicals. Activation volumes determined from high-pressure kinetic
      studies are inconclusive.

PMID- 14711001
TI  - The anti-parasitic effects of nitric oxide.
AB  - Endogenous and exogenous nitric oxide (NO) possesses antiparasitic effects on
      both Protozoa and Metazoa. However, NO production requires a tight control to
      limit cytotoxic damage to the host's own cells. The best known parasitic
      macromolecular targets for NO(-donors) are cysteine proteases, which are relevant
      in several aspects of the parasite life cycle and parasite-host relationships,
      and appear as promising targets for anti-parasitic chemotherapy.

PMID- 14711002
TI  - Nitric oxide signaling in plant-pathogen interactions.
AB  - Nitric oxide (NO), first characterized as an endothelium-derived relaxation
      factor, is involved in diverse cellular processes including neuronal signaling,
      blood pressure homeostasis, and immune response. Recent studies have also
      revealed a role for NO as a signaling molecule in plants. As a developmental
      regulator, NO promotes germination, leaf extension and root growth, and delays
      leaf senescence and fruit maturation. Moreover, NO acts as a key signal in plant
      resistance to incompatible pathogens by triggering resistance-associated
      hypersensitive cell death. In addition, NO activates the expression of several
      defense genes (e.g. pathogenesis-related genes, phenylalanine ammonialyase,
      chalcone synthase) and could play a role in pathways leading to systemic acquired
      resistance.

PMID- 14711003
TI  - Control of the nitric oxide-cytochrome c oxidase signaling pathway under
      pathological and physiological conditions.
AB  - Prominent among the mechanisms of interaction of nitric oxide (NO) with
      intracellular targets are the reactions with heme proteins. For example, the
      mechanism through which NO induces synthesis of the second messenger cyclic GMP
      involves the binding of NO to the heme in soluble guanylate cyclase. It has only
      recently been appreciated that NO binding to the binuclear oxygen binding site in
      cytochrome c oxidase may also serve as a signal transduction pathway. We
      postulate that NO is uniquely positioned to control mitochondrial respiration and
      in doing so regulates oxygen gradients within the cell. In this short overview
      the mechanisms of NO-dependent regulation of mitochondrial function will be
      discussed in the context of some of the biological and physiological
      consequences.

PMID- 14711004
TI  - Competitive, reversible, physiological? Inhibition of mitochondrial cytochrome
      oxidase by nitric oxide.
AB  - In the mid 1990s a number of research groups recognized that mitochondrial oxygen
      consumption could be reversibly inhibited by nitric oxide at the level of the
      enzyme cytochrome c oxidase. The inhibition was apparently competitive with
      respect to the oxygen concentration. This review critically assesses the present
      state of knowledge as regards the hypothesis that nitric oxide is a competitive,
      reversible, physiological inhibitor of cytochrome oxidase.

PMID- 14711005
TI  - Mitochondrial nitric-oxide synthase: role in pathophysiology.
AB  - The biochemistry of the mitochondrial production of nitric oxide is reviewed to
      gain insight into the basic role of this radical in mitochondrial and cellular
      oxidative metabolism. The mitochondrial production of nitric oxide is catalyzed
      by a nitric-oxide synthase (mtNOS). This enzyme has the same cofactor and
      substrate requirements as other constitutive nitric-oxide synthases. Its
      occurrence was demonstrated in various mitochondrial preparations from different
      organs and species using diverse approaches (oxidation of oxymyoglobin, electron
      paramagnetic resonance in conjunction with spin trap, radiolabeled L-arginine,
      immunohistochemistry, nitric-oxide electrode). MtNOS has been identified as the
      alpha isoform of nNOS, acylated at a Thr or Ser residue, and phosphorylated at
      the C-terminal end. Endogenous nitric oxide reversibly inhibits oxygen
      consumption and ATP synthesis by competitive inhibition of cytochrome oxidase.
      Nitric oxide is the first molecule that fulfills the requirement for a cytochrome
      oxidase activity modulator: it is a competitive inhibitor, produced endogenously
      at a fair rate near the target site, at concentrations high enough to exhibit an
      inhibitory effect on cytochrome oxidase. The role of the mitochondrial nitric
      oxide production is discussed in terms of the physiological (modulating oxygen
      gradients into tissues) and pathological (abrogation of oxygen gradient
      modification, apoptosis, protein nitrative/oxidative stress) implications.

PMID- 14711006
TI  - Nitric oxide and mitochondrial complex IV.
AB  - Micromolar nitric oxide (NO) rapidly (ms) inhibits cytochrome c oxidase in
      turnover with physiological substrates. Two reaction mechanisms have been
      identified leading, respectively, to formation of a nitrosyl- [a3(2+) -NO] or a
      nitrite- [a3(3+) -NO2-] derivative of the enzyme. In the presence of O2, the
      nitrosyl adduct recovers activity slowly, following NO displacement at k'
      approximately equal to 0.01 s(-1) (37 degrees C); the recovery of the nitrite
      adduct is much faster. Relevant to pathophysiology, the enzyme does not degrade
      NO by following the first mechanism, whereas by following the second one it
      promotes NO oxidation and disposal as nitrite/nitrate. The reaction between NO
      and cytochrome c oxidase has been investigated at different integration levels of
      the enzyme, including the in situ state, such as in mouse liver mitochondria or
      cultured human SY5Y neuroblastoma cells. The respiratory chain is inhibited by
      NO, either supplied exogenously or produced endogenously via the NO synthase
      activation. Inhibition of respiration is reversible, although it remains to be
      clarified whether reversibility is always full and how it depends on
      concentration of and time of exposure to NO. Oxygraphic measurements show that
      cultured cells or isolated state 4 mitochondria exposed to micromolar (or less)
      NO recover from NO inhibition rapidly, as if the nitrite reaction was
      predominant. Mitochondria in state 3 display a slightly more persistent
      inhibition than in state 4, possibly due to a higher accumulation of the nitrosyl
      adduct. Among a number of parameters that appear to control the switch over
      between the two mechanisms, the concentration of reductants (reduced cytochrome
      c) at the cytochrome c oxidase site has been proved to be the most relevant one.

PMID- 14711007
TI  - Mitochondria as targets of apoptosis regulation by nitric oxide.
AB  - In addition to their vital role as the cell's power stations, mitochondria exert
      an important function in apoptosis. In response to most if not all apoptosis
      inducers, mitochondrial membranes are permeabilized, leading to the release of
      potentially toxic proteins, mostly from the intermembrane space to the rest of
      the cells. Such pro-apoptotic intermembrane proteins include the caspase
      independent death effector AIF, as well as cytochrome c, which can trigger the
      activation of caspases, once it has reached the cytosol. The mitochondrial
      permeabilization process can be induced by a variety of different xenobiotics,
      via a direct effect on mitochondrial membranes. Alternatively, mitochondrial
      permeabilization can be induced by endogenous second messengers, which are
      elicited in response to stress. The permeabilization process is controlled by the
      mitochondrial permeability transition pore complex (PTPC), by proteins of the Bcl
      2/Bax family, as well as by lipids and metabolites. Nitric oxide (NO) is one of
      the second messengers that can trigger apoptosis by inducing mitochondrial
      membrane permeabilization. This effect may involve a direct effect on the PTPC
      and/or indirect effects secondary to the NO-mediated inhibition of oxidative
      phosphorylation. This has far-reaching implications for the pathophysiology of
      NO.

PMID- 14711008
TI  - NO production by Pseudomonas aeruginosa cd1 nitrite reductase.
AB  - The structural and catalytic properties of Pseudomonas aeruginosa cd1 nitrite
      reductase, a key enzyme in bacterial denitrification, are reviewed in this paper.
      The mechanism of reduction of nitrite to NO is discussed in detail with special
      attention to the structural interpretation of function. The ability to stabilize
      negatively charged molecules, such as the substrate (nitrite) and other ligands
      (hydroxide and cyanide), is a key feature of catalysis in cd1NIRs. The positive
      potential in the active site is largely due to the presence of the two conserved
      distal histidines, which are involved in both substrate binding and product
      release.

PMID- 14711009
TI  - Truncated hemoglobins and nitric oxide action.
AB  - Truncated hemoglobins (trHbs) build a separate subfamily within the hemoglobin
      superfamily; they are scarcely related by sequence similarity to (non-)vertebrate
      hemoglobins, displaying amino acid sequences in the 115-130 residue range. The
      trHb tertiary structure is based on a 2-on-2 alpha-helical sandwich, which hosts
      a unique hydrophobic cavity/tunnel system, traversing the protein matrix, from
      the molecular surface to the heme distal site. Such a protein matrix system may
      provide a path for diffusion of ligands to the heme. In Mycobacterium
      tuberculosis trHbN the heme-bound oxygen molecule is part of an extended hydrogen
      bond network including the heme distal residues TyrB10 and GlnE11. In vitro
      experiments have shown that M. tuberculosis trHbN supports efficiently nitric
      oxide dioxygenation, yielding nitrate. Such a reaction would provide a defense
      barrier against the nitrosative stress raised by host macrophages during lung
      infection. It is proposed that the whole protein architecture, the heme distal
      site hydrogen bonded network, and the unique protein matrix tunnel, are optimally
      designed to support the pseudo-catalytic role of trHbN in converting the reactive
      NO species into the harmless NO3-.

PMID- 14711010
TI  - Interplay of Cu,Zn superoxide dismutase and nitric oxide synthase in
      neurodegenerative processes.
AB  - Reactive oxygen and nitrogen species (ROS and RNS) have been extensively
      recognized as important signaling molecules implicated in physiological processes
      such as gene expression, cell differentiation and immune activation.
      Nevertheless, continuous production of these species may produce oxidative and/or
      nitrosative stress resulting in cell damage and ultimately leading to cell death.
      Due to the high oxygen consumption and relative poor antioxidant defense, the
      central nervous system is highly susceptible to ROS- and RNS-mediated toxicity.
      Actually, the oxidative and nitrosative stress have been implicated in the
      pathogenesis of neurodegeneration of a large variety of neurological disorders.
      This review will cover some aspects of the involvement of ROS- and RNS-mediated
      apoptotic processes occurring in cellular models of familial amyotrophic lateral
      sclerosis (FALS), in particular the cases associated with mutations in SOD1, the
      gene encoding Cu,Zn superoxide dismutase (Cu,Zn SOD). A possible role for
      proteasome in the inhibition of neurodegenerative process by balancing ROS and
      RNS species is envisaged on the basis of evidence provided by results obtained
      from studies on this experimental model.

PMID- 14711011
TI  - A role for endogenous electric fields in wound healing.
AB  - This review focuses on the experimental evidence supporting a role for endogenous
      electric fields in wound healing in vertebrates. Most wounds involve the
      disruption of epithelial layers composing the epidermis or surrounding organs in
      the body. These epithelia generate a steady voltage across themselves that will
      drive an injury current out of the wounded region, generating a lateral electric
      field that has been measured in four different cases to be 40-200 mV/mm. Many
      epithelial cells, including human keratinocytes, have the ability to detect
      electric fields of this magnitude and respond with directed migration. Their
      response typically requires Ca2+ influx, the presence of specific growth factors
      and intracellular kinase activity. Protein kinase C is required by neural crest
      cells and cAMP-dependent protein kinase is used in keratinocytes while mitogen
      activated protein kinase is required by corneal epithelial cells. Several recent
      experiments support a role for electric fields in the stimulation of wound
      healing in the developing frog neurula, adult newt skin and adult mammalian
      cornea. Some experiments indicate that when the electric field is removed the
      wound healing rate is 25% slower. In addition, nearly every clinical trial using
      electric fields to stimulate healing in mammalian wounds reports a significant
      increase in the rate of healing from 13 to 50%. However, these trials have
      utilized many different field strengths and polarities, so much work is needed to
      optimize this approach for the treatment of mammalian wounds.

PMID- 14711012
TI  - The role of mitotic checkpoint in maintaining genomic stability.

PMID- 14711013
TI  - The regulation of oocyte maturation.

PMID- 14711014
TI  - Stem cells: a promising source of pancreatic islets for transplantation in type 1
      diabetes.
AB  - Diabetes is a disease that affects millions and causes a major burden on the
      health care system. Type 1 diabetes has traditionally been managed with exogenous
      insulin therapy, however factors such as cost, lifestyle restriction, and life
      threatening complications necessitate the development of a more efficient
      treatment alternative. Pancreas transplantation, and more recently transplant of
      purified pancreatic islets, has offered the potential for independence from
      insulin injections. Islet transplantation is gaining acceptance as it has been
      shown to be effective for certain patients with type 1 diabetes. One obstacle,
      however, is the fact that there is an inadequate supply of cadaveric human islets
      to implement this procedure on a widespread clinical basis. A promising source of
      transplantable islets in the future will come through the use of adult or
      embryonic stem cells. This chapter presents an overview of the advancements made
      in the development of a stem cell based application to islet transplantation.
      Advantages and limitations are discussed regarding the use of embryonic stem
      cells, adult pancreatic stem/progenitor cells, and the use of nonpancreatic
      tissues based on current experimental models in the literature. It is concluded
      that stem cells offer the greatest potential for the development of an abundant
      source of pancreatic islets, although specific obstacles must be overcome before
      this can become a reality.

PMID- 14711015
TI  - Differentiation potential of adipose derived adult stem (ADAS) cells.

PMID- 14711016
TI  - Behind the scenes in arthritis care.

PMID- 14711017
TI  - The Wisconsin Arthritis Program--a new partnership to reduce the leading cause of
      disability.
AB  - There are known and effective strategies to prevent arthritis, reduce symptoms,
      decrease disability, and improve quality of life. For example: Weight management
      and physical activity may lower risk. Early diagnosis and appropriate self
      management may decrease pain. Arthritis Self-help Course, an evidence-based
      education program, may reduce pain and enhance self-management. The new Wisconsin
      Arthritis Program will engage citizens, health professionals, and organizations
      together as partners to reach more people in order to utilize effective
      strategies to prevent arthritis, reduce symptoms, decrease disability, and
      improve quality of life.

PMID- 14711018
TI  - Pain management in arthritis: evidence-based guidelines.

PMID- 14711019
TI  - The state of arthritis in Wisconsin.
AB  - Arthritis is the leading cause of disability and functional limitation in
      Wisconsin and trails only heart disease as the leading cause of work disability.
      In 2001, the estimated prevalence of arthritis/chronic joint symptoms (CJS) among
      US adults was 33%, representing approximately 69.9 million adults. Wisconsin has
      established a statewide program to address this chronic condition. Prior to its
      inception, no state-based arthritis surveillance was available. The Wisconsin
      Behavioral Risk Factor Surveillance System (BRFSS) first included questions on
      chronic joint symptoms and doctor-diagnosed arthritis in 2000. That data provides
      a baseline to describe the burden of arthritis in Wisconsin. This report
      summarizes the prevalence of arthritis and its distribution among Wisconsin
      adults. 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- 14711020
TI  - Obesity and physical inactivity among Wisconsin adults with arthritis.
AB  - INTRODUCTION: Arthritis is the leading cause of disability in Wisconsin, and
      affects approximately 34% of Wisconsin adults. Obesity is an established risk
      factor for arthritis; however, the relationship between arthritis and obesity has
      not been well characterized at the population level in Wisconsin. OBJECTIVES:
      Describe the relationship between arthritis, obesity, physical inactivity, and
      efforts to lose weight among Wisconsin adults. METHODS: Wisconsin Behavioral Risk
      Factor Surveillance System 2000-2001. Arthritis was defined by either doctor
      diagnosis or self-reported chronic joint symptoms. RESULTS: Overall, 36% of
      respondents had arthritis. Among adults with arthritis, 28% were obese (BMI>30)
      compared to 16% without arthritis. The prevalence of leisure time physical
      inactivity was substantially higher among those with arthritis compared to those
      without arthritis (27.8% vs. 19.2%). Although prevalence of obesity was higher
      among those with arthritis, only 46% of adults with arthritis made an effort to
      lose weight. CONCLUSIONS: A high proportion of adults with arthritis are obese
      and are physically inactive, even though studies have shown that weight loss and
      regular physical activity relieve arthritis symptoms. Efforts should be made to
      promote weight loss and physical activities among adults with arthritis.

PMID- 14711021
TI  - A new era in rheumatoid arthritis treatment.
AB  - Rheumatoid Arthritis (RA) is a systemic autoimmune disease that primarily
      manifests as a chronic symmetric polyarthritis. Treatment in the past was aimed
      at symptomatic pain relief. The initiation of disease modifying anti-rheumatic
      drugs (DMARDs) was historically started only after significant disease activity
      was present in order to reduce side effects from drug toxicities. Unfortunately,
      irreversible joint damage may occur early in the disease course. Evidence of bony
      destruction is common on radiographs within the first 2 years after disease
      onset. Therefore, more aggressive treatment became the standard with earlier
      introduction of DMARDs in hopes of preventing joint destruction. Within the past
      few years, greater understanding of the pathophysiology of RA has permitted
      development of therapies targeted at specific cytokines. Tumor Necrosis Factor
      alpha (TNF-alpha) is a pro-inflammatory cytokine believed to play a key role in
      the inflammatory response in RA. Three drugs--etanercept, infliximab, and
      adalimumab--are anti-TNF-alpha agents approved in the United States for the
      treatment of RA. This article is a review of indications, clinical trials, and
      toxicities of these 3 agents.

PMID- 14711022
TI  - Newer approaches to the treatment of rheumatoid arthritis.
AB  - Growing evidence suggests that rheumatoid arthritis should no longer be
      considered a benign disease. Considerable data suggest that this disease is
      associated with diminished long-term survival. Other studies have also shown that
      in patients with rheumatoid arthritis, bone damage can occur very early in the
      disease course. Older disease modifying agents for treating rheumatoid arthritis
      were limited by long-term toxicity. Newer agents, including methotrexate,
      leflunomide, and the biologic agents etanercept, infliximab, adalimumab, and
      anakinra have shown long-term efficacy and superior long-term tolerability. Newer
      approaches to treating this disease have stressed treatment early in the disease
      course, before irreversible joint damage occurs, using combinations of second
      line disease modifying agents.

PMID- 14711023
TI  - The epidemiology of agriculture-related osteoarthritis and its impact on
      occupational disability.
AB  - BACKGROUND: Hip and knee osteoarthritis and undiagnosed chronic joint pain are
      more prevalent in agricultural workers than other occupational groups,
      significantly impacting the ability of small farm operators and farm workers to
      maintain a livelihood. METHODS: Agricultural risk factors, economic impacts,
      national and state AgrAbility data, gender, and farm/non-farm prevalence
      differences of arthritis and joint arthropathy in a Wisconsin farm cohort are
      reviewed. RESULTS: Agricultural workers (primarily male) are at increased risk
      for developing osteoarthritis of the hip and knee. In Wisconsin, the prevalence
      rate of osteoarthritis is higher in a male farm vs. a male rural non-farm cohort.
      Arthritis comprises 10%-12% of the disability referrals to state and national
      AgrAbility programs. Back pain, joint injury, and orthopedic injury account for
      another 38%. The ability to perform agricultural job duties is significantly
      affected by arthritis and lack of access to health care. Obesity is an additional
      independent risk factor for osteoarthritis in the rural population. CONCLUSIONS:
      The agricultural work force is at particular risk for arthritis-related
      disability. Improved access to health care for diagnosis and treatment can lessen
      disability. Prevention of arthritis is multi-factorial, involving ergonomic
      improvements, lifestyle modification to prevent obesity, and adequate medical
      treatment of arthritis.

PMID- 14711024
TI  - Juvenile idiopathic arthritis: an update.
AB  - Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy of
      childhood. Previous terminology identified this entity as juvenile rheumatoid
      arthritis. The 7 subsets of JIA identified under the new classification system
      are discussed, as are current treatments. A differential diagnosis of JIA is
      included as this condition continues to be diagnosed by exclusion. Recent
      studies, which discuss the outcome of adults with previous childhood arthritis,
      are reviewed.

PMID- 14711025
TI  - Arthritis efforts at Medical College aimed at damage control, prevention.

PMID- 14711026
TI  - Make your retirement plan a priority.

PMID- 14711027
TI  - How to find the real one (at the level of pre-mRNA splicing).
AB  - The mature mRNA always carries nucleotide sequences that faithfully mirror the
      protein product according to the niles of the genetic code. However, in the
      chromosome, the nucleotide sequence that represents a certain protein is
      interrupted by additional sequences. Therefore, most eukaryotic genes are longer
      than their final mRNA products. The human genome project revealed that only a
      tiny portion of sequences serves as protein-coding region and almost one quarter
      of the genome is occupied by non-coding intervening sequences. The elimination of
      these non-coding regions from the precursor RNA in a process termed splicing must
      be extremely precise, because even a single nucleotide mistake may cause a fatal
      error. At present, two types of intervening sequences have been identified in
      protein-coding genes. One of them, the U2-dependent or major-class is prevalent
      and represents 99% of known sequences. The other one, the so-called U12-dependent
      or minor-class of introns, occurs in much lesser amounts in the genome. The basic
      problem of nuclear splicing concerns i/ the molecular mechanisms, which ensure
      that the coding regions are correctly recognized and spliced together: ii/ the
      principles and mechanisms that guarantee the high fidelity of the splicing
      system; iii/ the differences in the excision mechanisms of the two classes of
      introns. We are going to present models explaining how intervening sequences are
      accurately removed and the coding regions correctly juxtaposed. The two splicing
      mechanisms will also be compared.

PMID- 14711028
TI  - Autonomic nerves terminating on smooth muscle cells of vessels in the pineal
      organ of various mammals.
AB  - The significance of autonomic nerves reaching the pincal organ was already
      investigated in connection to the innervation of pinealocytes and mediating light
      information from the retina for periodic melatonin secretion. In earlier works we
      found that some autonomic nerve fibers are not secretomotor but terminate on
      arteriolar smooth muscle cells in the pineal organ of the mink (Mustela vison).
      Studying in serial sections the pineal organ of the mink and 15 other mammalian
      species in the present work, we investigated whether similar axons of vasomotor
      type are generally present in the wall of pineal vessels, further, whether they
      reach the organ via the conarian nerves or via periarterial plexuses. In all
      species investigated, axons of perivasal nerve bundles were found to form
      terminal enlargements on the smooth muscle layer of pineal arterioles. The
      neuromuscular endings contain several synaptic and some granular vesicles. Axon
      terminals are also present around pineal veins. In serial sections, we found that
      the so-called conarian autonomic nerves reach the pineal organ alongside pineal
      veins draining into the great internal cerebral vein. Similar nerves present near
      arteries of the arachnoid enter the pineal meningeal capsule and septa by
      arterioles, both perivenous and periarterial nerves form terminals of vasomotor
      type. The arteriomotor and venomotor regulation of the tone of the vessels of the
      pineal organ may serve the vascular support for circadian and circannual periodic
      changes in metabolic activity of the pineal tissue.

PMID- 14711029
TI  - Subcellular localization of components of the dystrophin glycoprotein complex in
      cultured retinal muller glial cells.
AB  - The dystrophin glycoprotein complex (DGC) is a membrane-associated protein
      complex binding extracellular matrix (ECM) molecules, such as laminin and forming
      a bridge towards the cytoskeleton. The molecular composition of the DGC is cell
      type dependent and it is involved in cell adhesion and motility. Here we present
      immunocytochemical localization of beta-dystroglycan, the central member of the
      DGC, utrophin and Dp71f, the spliced 71 kDa dystrophin protein product of the DMD
      gene, in cultured retinal Muller glial cells. It is shown that beta-dystroglycan
      and utrophin are colocalized in clusters in all parts of Muller cells including
      the lamellipodium and leading edge of migrating cells. As a contrast, Dp71f
      labels are distinct from beta-dystroglycan and confined to the perinuclear
      cytoplasm of Muller cells indicating that Dp71f is not a member of the DGC in
      cultured Muller cells.

PMID- 14711030
TI  - Mitochondrial DNA4977 deletion in brain of newborns died after intensive care.
AB  - Mitochondrial DNA (mtDNA) deletion affecting 4977 base pairs (mtDNA4977), the
      most common mtDNA mutation in humans, was analysed in brain specimens (frontal,
      temporal, and cerebellar cortices, caudate nucleus, thalamus, and hippocampus)
      and in other tissues (blood clot, liver, kidney, heart, and muscle) taken at
      autopsy of deceased neonates. mtDNA4977 deletion determined by polymerase chain
      reaction (PCR) could be demonstrated in each neonatal sample, however, quantity
      of mtDNA4977 deletion was less in the newborn samples than in those of the
      elderlies. Results obtained suggest that contrary to certain data mtDNA4977
      deletion can be present in neonates. The mtDNA4977 deletion could be generated by
      perinatal hypoxia or temporary oxygen oversaturations during the intensive care
      of the neonates, as the mtDNA is sensitive to oxidative damage. In combination
      with other factors an additional causative role of mtDNA4977 deletion reported
      here cannot be ruled out in development of cerebral palsy or mental retardation
      of unknown origin often seen in neonates underwent neonatal intensive care
      procedures.

PMID- 14711031
TI  - Size of the vomeronasal organ in wild Microtus with different mating strategies.
AB  - Most studies on mammalian vomeronasal organ (VNO) have been on laboratory-bred
      animals. Our present study examines the VNO in wild-caught meadow voles (Microtus
      pennsylvanicus: n=16) and prairie voles (M. ochrogaster: n=15). These species
      vary in their mating strategies and degree of parental care by males. M.
      ochrogaster exhibits pair bonding and more paternal care compared to M.
      pennsylvanicus, a promiscuous species. We hypothesize that sexual dimorphism will
      occur in the promiscuous species based on previous studies which suggest that
      those who exhibit more aggressive or masculine behavior have larger VNOs. Our
      results support our original finding that VNOs are not different in size in wild
      Microtus spp. that vary in male parental tendencies. However, the present study
      also indicates that M. pennsylvanicus, the species exhibiting more disparate
      parental tendencies, exhibited larger VNOs in females than males. This is the
      reverse of previous findings on rats, and we hypothesize that this difference may
      be due to mate selectivity and/or maternal aggression.

PMID- 14711032
TI  - Immunohistochemical analysis of substance P containing nerve fibres and their
      contacts with mast cells in the diabetic rat's tongue.
AB  - Sensory neuropathy is common symptom of the diabetes mellitus and the prevalence
      of oral lesions is higher in diabetic patients. The distribution of substance P
      was studied immunohistochemically in streptozotocin induced diabetic rat's
      tongue. The morphological association of sensory nerves (substance P
      immunoreactive) with mast cells (nerve fibre-mast cell contact) was monitored.
      The substance P nerve fibre mast cell contacts were very scanty in control
      tongue. The number of substance P nerve terminals and mast cells was
      significantly increased (p < 0.05) in diabetes mellitus after 4 weeks of the
      treatment compared with the control tongue. The number of mast cell nerve
      contacts was even more significantly increased (p < 0.001) in diabetes. The
      distance between nerve fibres and mast cells was about 1 mm and very often less
      than 200 nm. In some instances, the mast cells were degranulated in the vicinity
      to nerve fibres. Increased number of mast cell nerve contacts in neurogenic
      inflammation might cause vasoconstriction and lesions of the oral mucosa, so some
      disorders such lichen planus, leukoplakia and cancer might frequently develop in
      diabetes mellitus.

PMID- 14711033
TI  - A comparative methodical study of the faecal steroid analysis on birds: looking
      for a valid method of testosterone determination.
AB  - In a comparative study, a relatively simple and high sensitivity method was
      developed for analysis of testosterone-equivalent(s) in the faeces of different
      bird species. To determine the recovery of extractions and purifications, tritium
      labelled testosterone was added to the wet samples. Then the samples were treated
      with sodium dodecil sulphate (SDS), an emulsificator to "open-up" the complex,
      lipid-coated particles of faecal samples. This emulsification resulted in the
      decrease of the quantity of interfering substances after diethyl-ether extraction
      and the linearity of the measured testosterone equivalents from aliquots in the
      range of 2 and 10 mg of faeces. In the RIA, we applied a group specific
      polyclonal testosterone antibody which cross-reacted with reduced metabolites and
      at a certain level with sulphate conjugates as well. The use of Helix enzymes did
      not modified significantly the results of the analysis relating to a low level of
      conjugated androgens in the faecal extracts. The biological validity of the
      method was tested on domestic cockerels, where between the plasma and faecal
      testosterone values a four hours phase shift was observed, with a correlation of
      0.6355. This method is suitable for "non invasive", behavioural-ethological
      studies.

PMID- 14711034
TI  - Ultrastructural studies on the pheromone-producing cells in the silkmoth, Bombyx
      mori: formation of cytoplasmic lipid droplets before adult eclosion.
AB  - In Bombyx mori, pheromone-producing cells accumulate a number of lipid droplets
      in the cytoplasm preceding the production of the sex pheromone, bombykol. The
      process of lipid droplet formation in the pheromone-producing cells was
      investigated by using light and electron microscopy. Light microscopy revealed
      that the lipid droplets appeared from 2 days before adult eclosion and dramatic
      accumulation took place between 2 days and 1 day before eclosion. Electron
      microscopical studies revealed that smooth endoplasmic reticulum and numerous
      vesicles, their sizes being less than 1 microm, were detectable 2 days before
      eclosion, and some vesicles were fused with mitochondria at this stage. These
      characteristic changes in the pheromone-producing cells suggest that fatty acyl
      CoA synthesis following de novo fatty acid synthesis takes place at this time.
      Involutions in the basal plasma membrane of the cells occurred throughout the
      observed period, which were extensive on the day before adult eclosion. Besides
      extensive basal involutions, immature lipid droplets appeared and then mature
      fully electron-dense lipid droplets were observed on the day of adult eclosion.
      These ultrastructural observations, combined with recent physiological studies
      suggest, that the basal involutions presumably reflect the uptake of lipidic
      components required for the construction of lipid droplets, the function of which
      is to store the bombykol precursor and to provide it for bombykol biosynthesis in
      response to pheromonotropic stimuli by pheromone biosynthesis activating
      neuropeptide (PBAN).

PMID- 14711035
TI  - Effects of various hormones on the sexual maturity of European eel (Anguilla
      anguilla L.) females from farm and lakes.
AB  - Previously described and alternative methods of the induction of sexual
      maturation in the European eel were investigated. Weekly administrations of a
      gonadoliberin agonist (nnRH-A=D-Phe6-GnRH-Ea) did not induce statistically
      significant effect on the gonads of treated eels in none of the dosages used (0.1
      microg and 10 microg/fish). Carp pituitary extract and carp pituitary extract
      together with a dopamine antagonist caused considerable external changes
      (increase in eye size) and significant gonadal development in two treatment
      groups: wild and cultivated stocks. The induction of the ovulation by double
      amount of CP and gonadoliberin agonist with dopamine antagonist mixture was not
      successful in a wild stock. Fertilisation of stripped eggs of farm eel was
      attempted unsuccessfully in, due to low egg quality. An advanced phase of the
      sexual maturation process could be induced in specimen infected by Anguillicola
      crassus indicating, that nematode infection is not a limiting factor in the
      artificial propagation of the European eel.

PMID- 14711036
TI  - Identification and induction of hsp70 gene by heat shock and cadmium exposure in
      carp.
AB  - A member of the multi-gene family, encoding 70 kD stress proteins, was identified
      from the common carp (Cyprimus carpio). Homologies, observed at both nucleic acid
      and amino acid levels, and also the intronless structure of this gene, strongly
      suggest that it corresponds to a heat-inducible hsp70 gene in carp. Gene-specific
      primers were selected and used in RT-PCR reactions to measure the basal hsp70
      mRNA levels and to follow the inducer-specific expression of this gene in
      different tissues during in vivo studies. Carp hsp70 mRNA is not detectable in
      the brain and muscle, and its concentration is around the limit of detection in
      the kidney and liver of unstressed animals. The expression of hsp70 is induced by
      elevated temperature and it responds to Cd treatment in a tissue and time
      dependent manner.

PMID- 14711037
TI  - Effect of adrenalectomy on rat peritoneal macrophage response.
AB  - Glucocorticoid hormones are important for vital functions and act to modulate
      inflammatory and immune responses. In contrast to other hormonal systems no
      endogenous mediators have been identified that can directly counter-regulate
      their potent anti-inflammatory and immunosuppressive properties. Glucocorticoids
      are known to interfere with the ability of the macrophage not only to induce and
      amplify an immune response but also to inhibit macrophage inflammatory effector
      functions. Although the actual immunocompetence of animals undergoing endocrine
      gland ectomy has never been directly studied, there is no doubt that adrenal
      hormones are deeply involved in the development and maintenance of the immunitory
      functions and this may in turn influence the inflammatory reaction. To study the
      effect of endogenous glucocorticoids on the functions of rat peritoneal
      macrophages and induction of humoral immune response we observed some of the rat
      peritoneal macrophage effector functions, provided that endogenous
      glucocorticoids are depicted by adrenalectomy. The mean phagocytic index (PI) of
      control macrophage (Mphi) is increased from 23,825 +/- 427 to 31,895 +/- 83 after
      adrenalectomy (P < or = 0.001). Intracellular killing capacity in control cell is
      82% which is found to be 73% in case of adrenalectomised cell (p < 0.05). The
      amount of nitric oxide released from control Mphi 20.25 +/- 1 microM following
      adrenalectomy shows the amount of nitric oxide release was 18.25 microM (p < or =
      0.01 ). The percentage of DNA fragmentation in control Mphi was 68.82 +/- 4 which
      was reduced to 56.76 +/- 1 after adrenalectomy (p < or = 0.01). In sheep red
      blood cell (SRBC) immunised and adrenalectomised animal, agglutination titre was
      obtained at lowest antibody concentration (1 : 128) whereas serum from SRBC
      immunised normal rats showed early agglutination (1: 32). Endogenous
      glucocorticoid depleted rats show enhanced phagocytic capacity, antibody raising
      capacity as well as on the other hand adrenal hormone insufficiency reduces the
      intracellular killing capacity, nitric oxide (NO) release, improper cell
      maturation and heightens the probability of infection. These observations
      demonstrate a counter-regulatory system via glucocorticoid that functions to
      control inflammatory and immune responses.

PMID- 14711038
TI  - Quantitative evaluation of macrophage phagocytosing capacity by a fluorometric
      assay.
AB  - This paper reviews sensitive and simple quantitative evaluation of macrophage
      phagocytosing capacity by applying fluoresecin-labeled Sacharomyces cerevisiae
      cells. Yeast cells were conjugated with fluoresceinisothiocyanate (FITC) and used
      as fluorescent particles. A time course analysis within this method showed that
      phagocytosis of yeast cells was temperature dependent and that the number of that
      ones ingested by macrophages increased rapidly during the initial 60 min of
      incubation at 37 degrees C. Free fluorescent cells can be effectively removed by
      aspiration from the well. Furthermore, yeast cells required preopsonization with
      serum to achieve optimal uptake of the cells. The uptake of nonopsonized yeast
      cells by macrophages was significantly lower than that of opsonized cells (P <
      0.05). We propose that about 50% of mouse macrophages can carry functionally
      active FcR responsible for phagocytosis.

PMID- 14711039
TI  - Antidiuretic activity of aqueous bark extract of Sri Lankan Ficus racemosa in
      rats.
AB  - The decoction (D) of the bark of Ficus racemosa Linn (Family: Moraceae) is
      claimed as an antidiuretic by some Sri Lankan traditional practitioners. However,
      the validity of this claim has not been scientifically proven or refuted. The aim
      of this study was to evaluate the antidiuretic potential of D of the bark of F.
      racemosa (made as specified in traditional use) in rats using three doses (250,
      500 or 1000 mg/kg) following oral administration. The reference drug used was
      ADH. The results demonstrated both the low- and high-doses of D and ADH
      significantly impaired the total urine output. The D-induced antidiuresis had a
      rapid onset (within 1 h), peaked at 3 h and lasted throughout the study period (5
      h). However, antidiuretic potential of D was about 50% lower than that of ADH.
      The D was well tolerated even with subchronic administration. The D caused a
      reduction in urinary Na+ level and Na+/K+ ratio, and an increase in urinary
      osmolarity indicating multiple mechanisms of action. The results provide
      scientific support for its claimed antidiuretic action and deserve intensive
      scrutiny.

PMID- 14711040
TI  - Growth and developmental responses of potato to osmotic stress under in vitro
      conditions.
AB  - The effect of mannitol on different genotypes of potato was studied in callus and
      plantlet culture. In vitro responses of five potato genotypes with well-known
      field behaviour to water deficit were analysed. After a 4-week-long cultivation
      on media containing mannitol up to 0.8 M, different morpho-physiological
      parameters were determined and statistically analysed. The useful concentration
      of mannitol for in vitro screening the osmotic tolerance of different genotypes
      depended on the type of culture; it was 0.4 M in plantlet-test and 0.8 M in
      callus-test. In callus-test the relative increase of callus mass was a useful
      parameter for determination of osmotic tolerance of genotypes at cellular level.
      In plantlet culture, stress index calculated from the rate of surviving in vitro
      shoots, number and length of roots per surviving explant and the rate of rooted
      explants were applicable to determine three groups according to the tolerant,
      medium tolerant and sensitive categories in agreement with the field behaviour of
      these genotypes. Under in vitro stress conditions we were able to distinguish the
      examined genotypes with different drought tolerance.

PMID- 14711041
TI  - Evaluation of changes in the element content and biomass of invaded with
      Meloidogyne arenaria Tiny Tim tomato plants under NH4VO3 treatment.
AB  - The parasite-host system Meloidogyne arenaria--Tiny Tim tomato plants has been
      studied in order to investigate the influence of the process of invasion on the
      chemical composition and biomass of plants. The concentrations of seven chemical
      elements Cu, Zn, Mg, K, Na, Mn and Fe have been determined using AAS in controls
      and invaded plants, and their changes have been evaluated under treatment with
      NH4VO3 in three different concentrations 0.01, 0.1 and 0.13 mg/100 ml H2O. The
      process of treatment with NH4VO3 disbalances significantly the trace element
      content of plants. The lowest concentration (0.01 mg NH4VO3) causes bigger
      changes in the concentrations of Mn, Fe and Na in non-invaded plants. The highest
      concentration (0.13 mg NH4VO3) balances the content of the elements back to their
      levels in the control plants for the elements Zn, Fe and Na. The pure effect of
      the process of invasion with Meloidogyne arenaria on the biomass (leaves, stems,
      roots and total biomass) of Tiny Tim plants is expressed in a significant
      increasing, mainly due to the development of the parasites. After treatment with
      different concentrations of NH4VO3 the decreasing in the biomass of leaves, stems
      and roots is observed which reflects on the total biomass of plants. The
      concentration of NH4VO3 eliminates the unfavourable changes not only in the
      chemical content of plants but also in their biomass. It could be taken into
      consideration as an alternative method used instead of treatment with
      nematocides.

PMID- 14711042
TI  - Effects of acetylsalicylic acid on fresh weight pigment and protein content of
      bean leaf discs (Phaseolus vulgaris L.).
AB  - The effects of 100, 250, and 500 ppm acetylsalicylic acid solutions treatments on
      weight alteration, pigment and protein amounts in discs from the primary leaves
      of one month old bean (Phaseolus vulgaris L.) seedlings produced tinder
      greenhouse conditions are presented. The experiments show that: 100 ppm ASA had
      no significant influence (P > 0.05) but 250 and 500 ppm ASA caused an increase on
      weight loss (P < 0.01); ASA at higher concentrations (250 and 500 ppm),
      generally, caused a decrease on pigment amounts (P < 0.05-P < 0.01) but 100 ppm
      ASA had no considerably significant influence on them (P > 0.05), none of the ASA
      treatments caused a statistically significant influence on carotenoid amount (P >
      0.05); 100 and 250 ppm ASA treatments did not cause a significant influence on
      protein amount (P > 0.05). however 500 ppm ASA treatment caused an increase on
      protein injury (P < 0.05). Consequently, it is supposed that wet weight loss,
      pigment and protein injury have somewhat increased on leaf discs. depending on
      the toxic effect of high acetylsalicylic acid concentrations.

PMID- 14711043
TI  - Phylogenetic relationship of the genus Gilbertella and related genera within the
      order Mucorales based on 5.8 S ribosomal DNA sequences.
AB  - The complete ITS (internal transcribed spacer) region coding the ITS1, the ITS2
      and the 5.8S rDNA was amplified by polymerase chain reaction from two strains of
      Gilbertella persicaria, six strains in the Mucoraceae (Mucor piriformis, M.
      rouxii, M. circinelloides, Rhizomucor miehei, R. pusillus and R. tauricus) and
      four strains representing three species of the Choanephoraceae (Blakeslea
      trispora, Choanephora infundibulifera and Poitrasia circinans). Sequences of the
      amplified DNA fragments were determined and analysed. G. persicaria belongs to
      the monogeneric family (Gilbertellaceae), however, originally it was described as
      Choanephora persicaria. The goal of this study was to reveal the phylogenetic
      relationship among fungi belonging to Gilbertellaceae, Choanephoraceae and
      Mucoraceae. Our results support that the "intermediate" position of this family
      is between Choanephoraceae and Mucoraceae.

PMID- 14711044
TI  - When A. Rose is not A. Rose: the vagaries of author searching.
AB  - Creation of a faculty database is a challenging but worthwhile project. In 2002,
      librarians at the University of Missouri-Columbia were approached by the School
      of Medicine to create a database of faculty publications. This article outlines
      the project and gives special emphasis to the problems of author searching.
      Discussion items include author searching syntax and providing ideas for how to
      determine if a publication was written by a particular author.

PMID- 14711045
TI  - Making sense of autoimmune and rheumatic disorders at the reference desk.
AB  - This paper discusses concepts and terminology of some aspects of the autoimmune
      and rheumatic disorders as related to medical reference work. Details of
      anatomic, biochemical, and pathologic processes are not discussed. Knowledge of
      the specific terminology involved in this area may help to ensure a good approach
      to developing prudent strategies for database searching of the medical literature
      and, therefore, is reviewed. MeSH thesaurus terms are shown and textword synonyms
      are presented that provide tools for thorough searching techniques. Commonly used
      medical jargon as well as older terminology for this area is also explained.
      Examples of specific search strategies are illustrated.

PMID- 14711046
TI  - User satisfaction survey and usage of an electronic desktop document delivery
      service at an academic medical library.
AB  - In June 2000, the Biomedical Library at the University of South Alabama
      introduced Prospero, an electronic desktop document delivery service. From June
      2000 to November 2002, Prospero delivered 28% of interlibrary loan requests and
      72% of document delivery requests. In November 2002, the library conducted a user
      satisfaction survey of the Prospero service. Forty-two surveys were used. Fifteen
      responses were received from affiliated faculty, staff, and students, who
      generally expressed satisfaction with the service. Twenty-seven responses were
      received from unaffiliated users, comprised of medical libraries, individual
      users, and businesses. Based on the survey results, the library deemed the
      Prospero service a success. To better support users, the library's Web page was
      updated to include hardware and software requirements for successful use of the
      Prospero service, as well as screen shots of the Prospero process.

PMID- 14711047
TI  - Using clinical vignette assignments to teach medical informatics.
AB  - In response to curricular changes, many academic health sciences librarians have
      participated in curriculum planning and/or developed informatics course
      requirements for students enrolled at health sciences universities. This article
      describes the use of clinical vignette assignments, student journal club
      activities, and vignette-type multiple choice questions to teach and assess
      skills related to managing biomedical information, communicating effectively,
      basic computing, and life-long learning.

PMID- 14711048
TI  - ISI's Journal Citation Reports on the Web.
AB  - This column features an overview of the Institute for Scientific Information's
      (ISI) Journal Citation Reports (JCR) database. Basic searching techniques are
      presented, as well as simple ways to manipulate data contained in the file. The
      Journal Citation Reports database can provide information on highest impact
      journals, most frequently used journals, "hottest" journals, and largest journals
      in a field or discipline.

PMID- 14711049
TI  - Web-based PDA downloads for clinical practice guidelines and decision support
      tools.
AB  - The extraordinary volume of health-related information made available on the
      Internet comes at a high cost for effectively storing and accessing clinical
      information resources. Additionally, the ability to use critical patient care
      information is limited to the availability of computer access. Physicians and
      other health care professionals have readily adopted personal digital assistants
      (PDAs), also known as handheld computers, because the devices provide succinct
      critical patient care information at the point of need. Clinical practice
      guidelines available through the Internet for use with PDAs present health
      professionals, who have little time, with powerful information already formatted
      for point-of-care devices. This paper will review several strategies for finding
      and accessing point-of-care clinical information.

PMID- 14711050
TI  - New roles: professional staff sharing between a hospital and an academic library.
AB  - Childrens Hospital Los Angeles is a pediatric hospital and research institute
      affiliated with the Keck School of Medicine of the University of Southern
      California (USC). Historically, the library at Childrens Hospital was staffed by
      a hospital-employed librarian. In 1999, the library position was outsourced to
      USC's Norris Medical Library. The new position is staffed by a librarian who
      divides her time equally between two locations: the Childrens Hospital Library
      and the Norris Medical Library. This staff sharing arrangement has three primary
      goals: increase the collaboration between the libraries; improve access to
      resources and library staff expertise; and provide faster document delivery
      service to the Childrens Hospital library. This paper presents the details of the
      position, and addresses the pros and cons for both libraries and the librarian.

PMID- 14711051
TI  - Reinventing a health sciences digital library--organizational impact.
AB  - What is the organizational impact of becoming a digital library, as well as a
      physical entity with facilities and collections? Is the digital library an add-on
      or an integrated component of the overall library package? Librarians see
      sweeping environmental and technological changes. The staff members feel
      exhilarated and challenged by the pressures to adapt quickly and effectively.
      Librarians recognize that a Web presence, like other technology components, must
      be continuously enhanced and regularly re-engineered. The Health Sciences
      Library, University of North Carolina at Chapel Hill, is reinventing its digital
      presence to better meet the needs of the community. This paper provides a case
      study focusing on major changes in planning processes, organizational structure,
      staffing, budgeting, training, communications, and operations at the Health
      Sciences Library.

PMID- 14711052
TI  - Regulation of the immune response by the interaction of chemokines and proteases.

PMID- 14711053
TI  - Molecular mechanisms of host-pathogen interaction: entry and survival of
      mycobacteria in macrophages.

PMID- 14711054
TI  - B lymphoid neoplasms of mice: characteristics of naturally occurring and
      engineered diseases and relationships to human disorders.

PMID- 14711055
TI  - Prions and the immune system: a journey through gut, spleen, and nerves.
AB  - For more than two decades it has been contended that prion infection does not
      elicit immune responses: transmissible spongiform encephalopathies do not go
      along with conspicuous inflammatory infiltrates, and antibodies to the prion
      protein are typically undetectable. Why is it, then, that prions accumulate in
      lymphoid organs, and that various states of immune deficiency prevent peripheral
      prion infection? This review revisits the current evidence of the involvement of
      the immune system in prion diseases, while attempting to trace the elaborate
      mechanisms by which peripherally administered prions invade the brain and
      ultimately cause damage. The investigation of these questions leads to unexpected
      detours, including the neurophysiology of lymphoid organs, and even the function
      of a prion protein homolog in male fertility.

PMID- 14711056
TI  - Roles of the semaphorin family in immune regulation.
AB  - The immune system and the nervous system have distinct roles in maintaining
      physiological homeostasis. These independent systems, however, influence each
      other while sharing common resources, including the cytokines and members of the
      immunoglobulin superfamily. Semaphorins are one of these shared molecular
      families that are biologically active in both systems. Although semaphorins were
      originally identified as axon guidance factors functioning in the nervous system,
      recent studies have uncovered additional immunological functions. For example,
      ligand-receptor systems distinct from those characterized in the nervous system
      govern class IV semaphorin, CD100/Sema4D and Sema4A activity in immune responses.
      This review provides an overview of the currently emerging immunoregulatory
      functions of "Immuno-semaphorins."

PMID- 14711057
TI  - HLA-G molecules: from maternal-fetal tolerance to tissue acceptance.
AB  - Over the past few years, HLA-G, the non-classical HLA class I molecule, has been
      the center of investigations that have led to the description of its specific
      structural and functional properties. Although located in the HLA class I region
      of chromosome six, the HLA-G gene may be distinguished from other HLA class I
      genes by its low polymorphism and alternative splicing that generates seven HLA-G
      proteins, whose tissue-distribution is restricted to normal fetal and adult
      tissues that display a tolerogeneic function toward both innate and acquired
      immune cells. We review these points, with special emphasis on the role of HLA-G
      in human pathologies, such as cancer, viral infection, and inflammatory diseases,
      as well as in organ transplantation.

PMID- 14711058
TI  - The zebrafish as a model organism to study development of the immune system.

PMID- 14711059
TI  - Control of autoimmunity by naturally arising regulatory CD4+ T cells.
AB  - Naturally acquired immunological self-tolerance is not entirely accounted for by
      clonal deletion, anergy, and ignorance. It is now well established that the T
      cell-repertoire of healthy individuals harbors self-reactive lymphocytes with a
      potential to cause autoimmune disease and these lymphocytes are under dominant
      control by a unique subpopulation of CD4+ T cells now called regulatory T cells.
      Efforts to delineate these Treg cells naturally present in normal individuals
      have revealed that they are enriched in the CD25+ CD4+ population. The
      identification of the CD25 molecule as a useful marker for naturally arising CD4+
      regulatory T cells has made it possible to investigate many key aspects of their
      immunobiology, including their antigen specificities and the cellular/molecular
      pathways involved in their development and their mechanisms of action.
      Furthermore, reduction or dysfunction of the CD25+ CD4+ regulatory T cell
      population can be responsible for certain autoimmune diseases in humans.

PMID- 14711060
TI  - Epidemiologic trends in overweight and obesity.
AB  - Obesity in adults is associated with excess mortality and excess risk of coronary
      heart disease, hypertension, hyperlipidemia, diabetes, gallbladder disease,
      certain cancers, and osteoarthritis. Overweight children often become overweight
      adults, and overweight in adulthood is a health risk. Although childhood
      overweight may not always result in excess adult health risk, immediate
      consequences of overweight in childhood are psychosocial and also include
      cardiovascular risk factors such as hypertension, high cholesterol, and abnormal
      glucose tolerance. The causes of obesity are poorly understood, and both the
      prevention and the treatment of obesity are difficult. In this context, the
      ability to track epidemiologic trends in overweight and obesity is important.

PMID- 14711061
TI  - The genetics of obesity.
AB  - Obesity prevalence has increased markedly over the past few decades. The obesity
      pandemic has huge implications for public health and our society. Although
      multiple studies show that the genetic contribution to obesity is significant,
      our genes have not changed appreciably over this time period. It was hypothesized
      that natural selection favors genotypes that result in a thrifty metabolism
      because individuals who carry these genotypes would be more likely to survive
      times of nutrient scarcity and to pass these genotypes to successive generations.
      Now that most of the world has adopted an increasingly "obesigenic" lifestyle of
      excess caloric intake and decreased physical activity, these same genes
      contribute to obesity and poor health. With the exception of the rare mutations
      that cause severe morbid obesity, it seems that numerous genes, each with modest
      effect, contribute to an individual's predisposition toward the more common forms
      of obesity. Variants in several candidate genes have been identified: association
      analyses and functional studies show that they contribute to modest obesity and
      related phenotypes. More recently, insights regarding gene-gene interactions have
      begun to emerge. Genome-wide scans for obesity phenotypes have led to the
      identification of several chromosome regions that are likely to harbor obesity
      susceptibility genes. Because of the increasing number of genome scans, several
      regions of replication have emerged. Positional cloning of these genes will
      undoubtedly unveil new insights into the molecular and pathophysiologic
      mechanisms of energy homeostasis and obesity.

PMID- 14711062
TI  - Risks of obesity.
AB  - Obesity is a chronic disease caused by an imbalance between the energy ingested
      in food and the energy expended. Enlarged fat cells produce the clinical problems
      associated with obesity either because of the weight or mass of the extra fat or
      because of the increased secretion of free fatty acids and numerous peptides from
      enlarged fat cells. The consequence of these two mechanisms is other diseases,
      such as diabetes mellitus, gallbladder disease, osteoarthritis, heart disease,
      and some forms of cancer. The spectrum of medical, social, and psychologic
      disabilities includes a range of medical and behavioral problems.

PMID- 14711063
TI  - Obesity and type 2 diabetes.
AB  - The increasing prevalence of obesity is accompanied by an increasing prevalence
      of type 2 diabetes. Obesity not only increases the risk of developing type 2
      diabetes but also compounds its health risks and complicates its management. The
      health benefits of weight loss and the efficacy of current weight loss strategies
      in obese persons with type 2 diabetes are evaluated. In addition, the article
      reviews the results of lifestyle intervention trials designed to reduce
      conversion to type 2 diabetes in at-risk individuals.

PMID- 14711064
TI  - Obesity and hypertension.
AB  - This article has discussed some of the mechanisms involved in the causal relation
      between obesity and hypertension. Obesity causes a constellation of maladaptive
      disorders that individually and synergistically contribute to hypertension, among
      other cardiovascular morbidities. Well-designed population-based studies are
      needed to assess the individual contribution of each of these disorders to the
      development of hypertension. In addition, because the control of obesity may
      eliminate 48% of the hypertension in whites and 28% in blacks, this article has
      offered an up-to-date on the management of this problem. It is hoped that this
      article will help scientists formulate a thorough understanding of obesity
      hypertension and form the basis for more research in this field, which has a huge
      impact on human life.

PMID- 14711065
TI  - Obesity and dyslipidemia.
AB  - The primary dyslipidemia related to obesity is characterized by increased
      triglycerides, decreased HDL levels, and abnormal LDL composition. Much work has
      been done to elucidate the pathogenesis of the dyslipidemia of obesity, which
      seems to be closely related to insulin resistance in obese individuals; however,
      more studies in humans are needed to further understand the metabolic mechanisms
      underlying the changes, and to distinguish between the roles of insulin
      resistance and body fat in the lipoprotein changes. The dyslipidemia associated
      with obesity no doubt plays a major role in the development of atherosclerosis
      and CVD in obese individuals. All of the components of the dyslipidemia,
      including higher triglycerides, decreased HDL levels, and increased small, dense
      LDL particles, have been shown to be atherogenic. Weight loss and exercise, even
      if they do not result in normalization of body weight, can improve this
      dyslipidemia and thus reduce CVD risk. In addition, obese individuals should be
      targeted for intense lipid-lowering therapy, when necessary.

PMID- 14711066
TI  - Obesity and obstructive sleep apnea.
AB  - There is a very high prevalence of OSA in obese individuals and a high prevalence
      of obesity in patients with OSA. The pathophysiology of OSA is intimately linked
      to obesity. Anatomic and functional considerations of the pharyngeal airway, the
      CNS, central obesity, and leptin likely interact in the development of OSA in
      obese individuals. OSA may itself predispose individuals to worsening obesity
      because of sleep deprivation, daytime somnolence, and disrupted metabolism. The
      diagnosis of OSA requires the clinician's awareness of its potential to cause a
      spectrum of acute and chronic neurocognitive, psychiatric, and nonspecific
      symptoms in patients who may be unaware that their sleep is disturbed. Symptoms
      and examination findings help predict which obese individuals have OSA, and
      polysomnography is the gold standard by which to make the diagnosis and assess
      the effects of treatment. Numerous disease states are associated with both OSA
      and obesity, and it is becoming clear that the relationships are mediated by
      complex interrelated mechanisms. Common diseases and disease mechanisms in OSA
      and obesity suggest that conditions related to obesity may be better managed if
      patients, particularly those who are morbidly obese, are evaluated and treated
      for previously undiagnosed OSA. OSA is cured in only specific cases with
      craniofacial or upper airway surgery, and the general application of UVP is not
      efficacious. OSA also can be cured with sufficient lifestyle-mediated or surgical
      weight loss; however, in the absence of long-term weight maintenance, OSA returns
      with weight gain. Although not curative, nasal CPAP is the initial treatment of
      choice for most patients because of its noninvasive approach and technical
      efficacy. It is limited, however, by patient acceptance and long-term compliance.
      Advances in mask comfort and use of humidified air should increase its
      acceptance. Future management strategies include newer generations of positive
      airway devices that automatically titrate pressures (which are not yet
      recommended by expert organizations) and multidisciplinary approaches to managing
      the care of patients with OSA.

PMID- 14711067
TI  - Obesity and endocrine disease.
AB  - Several endocrine abnormalities are reported in obesity. Some of these
      abnormalities are considered as causative factors for the development of obesity,
      whereas others are considered to be secondary effects of obesity and usually are
      restored after weight loss. Thyroid hormones usually are normal in obesity, with
      the exception of T3 which is elevated. Prolactin is normal but prolactin response
      to different stimuli is blunted. GH is low and GH response to stimuli is blunted.
      IGF-I levels are normal or elevated. Cortisol, ACTH, and urine free cortisol
      levels are usually normal; however, a hyperresponsiveness of the HPA axis with
      increased cortisol and ACTH response to stimulatory tests is observed in
      centrally obese individuals. Total testosterone and SHBG levels are low, but free
      testosterone levels are usually normal in obese men. LH and FSH levels usually
      are normal and estrogens are elevated. Norepinephrine levels are elevated,
      whereas epinephrine levels are low or normal. Aldosterone levels are elevated but
      renin activity is usually normal. Parathyroid hormone levels are elevated with
      normal serum calcium levels and increased urine calcium levels. Monogenic
      mutations that result in severe obesity have been described in several
      individuals. Also, several endocrine diseases have obesity as one their clinical
      manifestations. Hypothyroidism, Cushing's syndrome, GH and testosterone
      deficiency, polycystic ovarian syndrome, insulinoma, hypothalamic lesions, and
      genetic syndromes often present with obesity. In most of these conditions,
      appropriate treatment of the primary disease results in weight loss. In addition,
      the fat cell has been found to be an endocrine organ that produces several
      peptides that are bioactive and participate in the regulation of adipocyte
      function.

PMID- 14711068
TI  - Assessment of the obese patient.
AB  - Obesity may be the most significant medical problem that health care providers
      will face over the coming decades. Physicians must aggressively address this
      chronic disease, providing both preventive and therapeutic care. Because this
      topic traditionally has not been taught in medical schools, physicians need to
      acquire the knowledge, skills, and attitudes necessary to be effective obesity
      care providers. Performing a detailed initial assessment, including an obesity
      focused history, physical examination, and selected laboratory and diagnostic
      tests, is fundamental to the process of care.

PMID- 14711069
TI  - Medical nutrition therapy for the treatment of obesity.
AB  - Most physicians do not have the benefit of in-house registered dietitians to
      facilitate patient evaluation and create treatment plans. Fortunately, with the
      new tools that are available to physicians and patients, energy balance can be
      evaluated. Then, a balanced deficit diet can be encouraged to achieve a weight
      management goal while maintaining healthy food intake patterns. Patients should
      also be counseled regarding weight maintenance diets to prevent weight gain. A
      low-fat diet is preferred because the patient will benefit from improved cardiac
      risk as a result of weight loss and a restricted saturated fat content is
      healthier. Other diets and approaches are acceptable if they are hypocaloric and
      do not negatively impact the patient's health (eg, some high-protein, high-fat
      diets can increase lipid levels; high-carbohydrate diets can increase
      triglycerides in patients who have type 2 diabetes). As patients lose weight,
      further increases in physical activity and exercise should be emphasized to help
      maintain lost weight. It is also helpful from a behavioral perspective to
      encourage patients to monitor their weight, food intake, and physical activity.
      Medical offices can support patients by providing weekly or biweekly weigh-ins to
      track progress and provide ongoing feedback. Patients should be reminded that the
      ultimate goal of any weight management program is gradual, incremental weight
      losses that are maintained over time. Sustainable and enjoyable changes in eating
      practices and physical activity patterns must be made along with a lifelong
      commitment to health.

PMID- 14711070
TI  - Exercise in the treatment of obesity.
AB  - Exercise is an important component of behavioral weight control interventions,
      and exercise may be most effective for weight control when combined with
      modifications to energy intake. Clinicians should initially encourage overweight
      and obese adults to adopt at least 150 minutes of moderate-intensity exercise per
      week (30 min x 5 d/wk), because this level of exercise has been shown to improve
      health-related outcomes. Higher levels of exercise, however, may be necessary to
      enhance long-term weight loss and to facilitate weight loss maintenance. It is
      now recommended that exercise be progressively increased to approximately 300
      minutes per week (60 min x 5 d/wk) to optimize the impact of exercise on body
      weight regulation. Adoption of this high level of exercise may be challenging,
      however, and therefore clinicians should counsel patients to incorporate
      intermittent and lifestyle approaches for exercise to maximize adherence.
      Moreover, devices such as pedometers may facilitate goal-setting and self
      monitoring of exercise, and these are critical components of effective behavioral
      interventions. Incorporation of these recommendations may increase the likelihood
      of clinicians' prescribing exercise for overweight and obese adults to
      effectively manage their body weight.

PMID- 14711071
TI  - Behavioral treatment of obesity.
AB  - Behavioral treatment for obesity seeks to identify and modify eating, activity,
      and thinking habits that contribute to patients' weight problems. This approach
      recognizes that body weight is affected by factors other than behavior, which
      include genetic, metabolic, and hormonal influences. Behavioral treatment helps
      obese individuals develop a set of skills (eg, a low-fat diet, a high-activity
      lifestyle, realistic expectations) to regulate weight, even though patients may
      remain overweight after treatment. This article describes the behavioral
      treatment of obesity, its short- and long-term results, and methods to improve
      long-term weight loss.

PMID- 14711072
TI  - Obesity and pharmacologic therapy.
AB  - Obesity is a chronic, complex, multifactorial disorder with increasing prevalence
      in modern society. Lifestyle modification has had limited success in treating
      this disorder. Currently approved pharmacologic treatments for obesity include
      sibutramine and orlistat, which have been associated with significantly greater
      weight loss than that seen with dieting alone. In addition, a greater percentage
      of patients who receive medical treatment achieve weight losses of more than 5%
      to 10% of their initial body weight. This weight loss is associated with
      improvements in blood pressure, insulin sensitivity, and dyslipidemia. Multiple
      new therapies that target several different regulatory pathways are currently in
      clinical trials.

PMID- 14711073
TI  - Basic pharmacodynamics of antibacterials with clinical applications to the use of
      beta-lactams, glycopeptides, and linezolid.
AB  - Time above MIC for free drug concentrations is the important PK-PD parameter
      correlating with the efficacy of beta-lactam antibiotics. The duration of time
      plasma concentrations needed to exceed the MIC is relatively similar for most
      organisms except staphylococci. Neutrophils contribute very little to the overall
      activity of beta-lactams. The appearance of increasing antimicrobial resistance
      can challenge the efficacy of these drugs when concentrations do not exceed the
      MIC for 40% to 50% of the dosing interval. Time above MIC with oral amoxicillin
      and amoxicillin-clavulanate can be enhanced with high-dose formulations. Time
      above MIC with parenteral preparations can be enhanced by longer intravenous
      infusions or even continuous infusion. The 24-hour AUC-MIC is probably the
      important PK-PD parameter correlating with the efficacy of vancomycin and
      teicoplanin. It clearly is the important parameter for the efficacy of linezolid.
      Usual doses of these drugs generally provide adequate plasma concentrations to
      treat effectively infections in which plasma concentrations are predictive of
      tissue concentrations. Penetration of these drugs into respiratory secretions,
      such as ELF, is enhanced for linezolid and reduced for vancomycin. This may give
      linezolid an advantage over vancomycin in certain respiratory infections.

PMID- 14711074
TI  - Pharmacodynamics and dosing of aminoglycosides.
AB  - Aminoglycosides are concentration-dependent killing agents whose pharmacodynamic
      predictors of efficacy are the area-under-the-curve to minimum inhibitory
      concentration ratio and the peak to minimum inhibitory concentration ratio.
      Prospective studies have shown that these agents can be given once-daily or less
      frequently in most clinical settings, with equal efficacy and possible reduced
      toxicity. Dosages for different clinical settings have been studied and methods
      are available to monitor once-daily dosing.

PMID- 14711075
TI  - Clinical pharmacodynamics of quinolones.
AB  - An understanding of fundamental PK-PD principles forms the basis for the rational
      use of antimicrobial agents. For quinolones, the fAUC24:MIC ratio is predictive
      of efficacy in animal and in vitro infection models, and in infected patients.
      The magnitude of the fAUC24:MIC ratio predictive of efficacy in animal and in
      vitro infection models has been shown to be concordant with those obtained from
      human data. By accounting for PK and microbiologic variability together with PK
      PD targets associated with efficacy or resistance suppression by Monte Carlo
      simulation, it is possible to discriminate between therapeutic regimens and
      select those regimens likely to be of greater benefit to patients. The maturation
      of antimicrobial PK-PD as a scientific discipline continues to accelerate and
      currently impacts clinical practice, drug development, and regulatory decision
      making.

PMID- 14711076
TI  - Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical
      applications.
AB  - Although the polymyxins seem attractive because of their unique structure and
      mechanism of action, relatively little is known about this group of antibiotics.
      Much of the available information is from a different era of medical practice
      when the manipulation of dosing strategies, or optimization of pharmacodynamic
      parameters, was not commonplace. Moreover, the more recent information that is
      available is limited in scope with regards to patient populations and
      microorganisms.

PMID- 14711077
TI  - Impact of pharmacodynamics on dosing of macrolides, azalides, and ketolides.
AB  - The study of pharmacodynamics characterizes the relationship between changing
      drug concentrations over time and antimicrobial and toxicologic effects and
      thereby offers a targeted approach to the design of dosing regimens for many
      antimicrobials. Distinct patterns of antimicrobial dynamics have been elucidated
      from these relationships and pharmacodynamic parameters (peak-MIC, AUC-MIC, T >
      MIC) have been used to quantify antimicrobial effects in relation to drug
      exposure. These relationships can be used to predict efficacy of a given dosing
      regimen. The accuracy of these predictions is influenced, in part, by the
      completeness of the model in which they are studied. This article discusses
      various in vitro and in vivo studies and clinical data that have contributed to
      the understanding of pharmacodynamics of the macrolides, azalides, and ketolides.

PMID- 14711078
TI  - Impact of pharmacodynamics on breakpoint selection for susceptibility testing.
AB  - In their report, Ericsson and Sherris stated that "adequately described
      sensitivity categorization schemes have been based on four main concepts" and
      went on to describe the advantages and inherent limitations of those four
      criteria. These limitations are very comparable with what is increasingly viewed
      as limitations to the current breakpoint systems because those four concepts have
      always been tried to be brought together in one breakpoint system. In line of
      this development, the European Committee on Antimicrobial Susceptibility Testing
      has recently recognized that clinical breakpoints based on PK-PD relationships
      confer a different meaning to resistance than early detection of microorganisms
      that do not belong to the natural bacterial population, but somehow have acquired
      resistance mechanisms and have introduced a wild-type cutoff breakpoint conveying
      a different meaning than clinical breakpoint. Similarly, there is increasing
      worry on the setting of clinical breakpoints based on frequency distributions
      because they do not bear an optimal relationship between dose and bacteriologic
      or clinical effect. This is especially apparent for older drugs because PK-PD was
      not used until a few years ago. Because dose-effect relationships have now been
      reasonably well established for most drugs, these should now be used to
      reappraise current clinical breakpoints.

PMID- 14711079
TI  - Antimicrobial tissue concentrations.
AB  - The clinical outcome of anti-infective treatment is determined by both PK and PD
      properties of the antibiotic. Only the free tissue concentrations of antibiotics
      at the target site, which are usually lower than the total plasma concentrations,
      are responsible for therapeutic effect. The free antibiotic concentrations at the
      site of action are a more appropriate PK input value for PK-PD analysis. The
      unbound tissue concentrations can be measured directly by microdialysis. Using
      plasma concentrations overestimates the target site concentrations and its
      clinical efficacy. The optimal dosing regimens of antibiotics have an impact on
      patients' outcome and cost of therapy, and reduce the emergence of resistance.

PMID- 14711080
TI  - Intracellular pharmacodynamics of antibiotics.
AB  - This article establishes the pharmacokinetic-pharmacodynamic parameters that are
      important when considering the intracellular activity of antibiotics. Generally
      speaking, the main classes of antibiotics seem to share globally the same
      properties against extracellular and intracellular organisms. The specific
      cellular pharmacokinetic properties may modulate those parameters so as to let
      other ones to become critical. Simple rules, such as equating accumulation and
      activity, are certainly incorrect, and other determinants need to be added to the
      equation. Finally, this article emphasizes the fact that much remains to be done
      in this area before rational therapeutic choices can be made.

PMID- 14711081
TI  - Clinical pharmacodynamics of antifungals.
AB  - Application of pharmacodynamic principles to antifungal drugs has provided an
      understanding of the relationship between drug dosing and treatment outcomes
      similar to that observed in antibacterial pharmacodynamics. Initial observations
      with triazole pharmacodynamics have correlated with clinical trial results and
      proved useful for validation of in vitro susceptibility breakpoints.
      Pharmacodynamic studies have been invaluable for clinical trial dosing design for
      numerous antibacterial drugs in the development stage. More recently,
      pharmacodynamics has been used for the development of treatment guidelines.
      Although there remain many unanswered questions regarding antifungal
      pharmacodynamics, available data suggest usefulness in the application of
      pharmacodynamics to antifungal clinical development.

PMID- 14711082
TI  - Pharmacodynamics and clinical use of anti-HIV drugs.
AB  - Antiretroviral drug exposure has been linked to both antiviral efficacy and the
      development of toxicity and further research in this area is ongoing and
      necessary. Use of these data may have important implications for TDM of HAART
      regimens in clinical practice. TDM, in conjunction with an assessment of the
      patient's viral resistance in the form of an IQ, needs to be examined and
      validated in large clinical trials.

PMID- 14711083
TI  - Cryptic organelles in parasitic protists and fungi.
AB  - A number of parasitic protists and fungi have adopted extremely specialised
      characteristics of morphology, biochemistry, and molecular biology, sometimes
      making it difficult to discern their evolutionary origins. One aspect of several
      parasitic groups that reflects this is their metabolic organelles, mitochondria
      and plastids. These organelles are derived from endosymbiosis with an alpha
      proteobacterium and a cyanobacterium respectively, and are home to a variety of
      core metabolic processes. As parasites adapted, new demands, or perhaps a
      relaxation of demands, frequently led to significant changes in these organelles.
      At the extreme, the organelles are degenerated and transformed beyond
      recognition, and are referred to as "cryptic". Generally, there is no prior
      cytological evidence for a cryptic organelle, and its presence is only discovered
      through phylogenetic analysis of molecular relicts followed by their localisation
      to organelle-like structures. Since the organelles are derived from eubacteria,
      the genes for proteins and RNAs associated with them are generally easily
      recognisable, and since the metabolic activities retained in these organelles are
      prokaryotic, or at least very unusual, they often serve as an important target
      for therapeutics. Cryptic mitochondria are now known in several protist and
      fungal parasites. In some cases (e.g., Trichomonas), well characterised but
      evolutionarily enigmatic organelles called hydrogenosomes were shown to be
      derived from mitochondria. In other cases (e.g., Entamoeba and microsporidia),
      "amitochondriate" parasites have been shown to harbour a previously undetected
      mitochondrial organelle. Typically, little is known about the functions of these
      newly discovered organelles, but recent progress in several groups has revealed a
      number of potential functions. Cryptic plastids have now been found in a small
      number of parasites that were not previously suspected to have algal ancestors.
      One recent case is the discovery that helicosporidian parasites are really highly
      adapted green alga, but the most spectacular case is the discovery of a plastid
      in the Apicomplexa. Apicomplexa are very well-studied parasites that include the
      malaria parasite, Plasmodium, so the discovery of a cryptic plastid in
      Apicomplexa came as quite a surprise. The apicomplexan plastid is now very well
      characterised and has been shown to function in the biosynthesis of fatty acids,
      isopentenyl diphosphate and heme, activities also found in photosynthetic
      plastids.

PMID- 14711084
TI  - Phylogenetic insights into the evolution of parasitism in hymenoptera.
AB  - The Hymenoptera are one of the four megadiverse orders of insects, with over
      100000 described species and several times this number still waiting to be
      described. A major part of this diverse group is formed of large lineages of
      parasitoid wasps. Some of these lineages have in turn given rise to subgroups
      that have gone on to diversify into other lifestyles, such as gall-forming on,
      and pollination of, plants, as well as a broad array of food-collecting behaviors
      associated with social living in colonies. Thus, the Hymenoptera demonstrate the
      large evolutionary potential of parasitism as a lifestyle, in contrast to early
      assertions that parasitism tends to lead to evolutionary 'dead ends' driven by
      overspecialization. Phylogenetic approaches have already led to a number of
      important insights into the evolution of parasitism in Hymenoptera. A series of
      examples are discussed in this review, including the origin of parasitism in the
      order, the development of koinobiosis in some groups, coevolution with symbiotic
      viruses, and the evolution in some groups away from parasitism and into such
      habits as gall formation, pollination of figs, nest building and sociality. The
      potential for comparative analysis of hymenopteran habits is large, but progress
      is still in its early stages due to the paucity of available well-supported
      phylogenies, and the still limited accumulation of basic biological data for many
      taxa.

PMID- 14711085
TI  - Nematoda: genes, genomes and the evolution of parasitism.
AB  - Nematodes are remarkably successful, both as free-living organisms and as
      parasites. The diversity of parasitic lifestyles displayed by nematodes, and the
      diversity of hosts used, reflects both a propensity towards parasitism in the
      phylum, and an adaptability to new and challenging environments. Parasitism of
      plants and animals has evolved many times independently within the Nematoda.
      Analysis of these origins of parasitism using a molecular phylogeny highlights
      the diversity underlying the parasitic mode of life. Many vertebrate parasites
      have arthropod-associated sister taxa, and most invade their hosts as third stage
      larvae: these features co-occur across the tree and thus suggest that this may
      have been a shared route to parasitism. Analysis of nematode genes and genomes
      has been greatly facilitated by the Caenorhabditis elegans project. However, the
      availability of the whole genome sequence from this free-living rhabditid does
      not simply permit definition of 'parasitism' genes; each nematode genome is a
      mosaic of conserved features and evolutionary novelties. The rapid progress of
      parasitic nematode genome projects focussing on species from across the diversity
      of the phylum has defined sets of genes that have patterns of evolution that
      suggest their involvement with various facets of parasitism, in particular the
      problems of acquisition of nutrients in new hosts and the evasion of host immune
      defences. With the advent of functional genomics techniques in parasites, and in
      particular the possibility of gene knockout using RNA interference, the roles of
      many putative parasitism genes call now be tested.

PMID- 14711086
TI  - Life cycle evolution in the digenea: a new perspective from phylogeny.
AB  - We use a new molecular phylogeny, developed from small and large subunit
      ribosomal RNA genes, to explore evolution of the digenean life cycle. Our
      approach is to map character states on the phylogeny and then use parsimony to
      infer how the character evolved. We conclude that, plesiomorphically, digenean
      miracidia hatched from eggs and penetrated gastropod first intermediate hosts
      externally. Fork-tailed cercariae were produced in rediae and emerged from the
      snail to be eaten directly by the teleost definitive host. These plesiomorphic
      characters are seen in extant Bivesiculidae. We infer that external encystment
      and the use of second intermediate hosts are derived from this behaviour and that
      second intermediate hosts have been adopted repeatedly. Tetrapod definitive hosts
      have also been adopted repeatedly. The new phylogeny proposes a basal dichotomy
      between 'Diplostomida' (Diplostomoidea, Schistosomatoidea and Brachylaimoidea)
      and 'Plagiorchiida' (all other digeneans). There is no evidence for coevolution
      between these clades and groups of gastropods. The most primitive life cycles are
      seen in basal Plagiorchiida. Basal Diplostomida have three-host life cycles and
      are associated with tetrapods. The blood flukes (Schistosomatoidea) are inferred
      to have derived their two-host life cycles by abbreviating three-host cycles.
      Diplostomida have no adult stages in fishes except by life cycle abbreviation. We
      present and test a radical hypothesis that the blood-fluke cycle is plesiomorphic
      within the Diplostomida.

PMID- 14711087
TI  - Progress in malaria research: the case for phylogenetics.
AB  - Malaria, from the Italian for "bad air", is a term used to describe a human
      disease caused by any of four parasites of the genus, Plasmodium. There are in
      fact over 200 described species of Plasmodium that parasitize reptiles, birds,
      and mammals, and may or may not cause disease in these various hosts. In this
      chapter, we highlight important evolutionary studies that have been undertaken to
      determine the relatedness among these species and their place in the taxonomic
      hierarchy. We begin by providing an overview of our present understanding of the
      phylum to which malaria parasites belong--Apicomplexa. The unique characteristics
      of these parasites reflect both their adaptation to the parasitic life style as
      well as some vestigial remnants of their pre-parasitic evolutionary past.
      Phylogenetic analyses provide the means for discerning the means by which these
      characteristics have come into existence. We next discuss the systematics of the
      genus Plasmodium. Morphology, genomic structure and content as well as host
      affiliation of these parasites are all traits that have been used for
      establishing taxonomic arrangements. Molecular phylogenetics has proven to be an
      invaluable tool in this regard and so we discuss the current phylogenetic picture
      of the genus as well as the correspondence among the various datasets
      (morphology, molecules, and host-preference). Lastly, we present a detailed
      account of our current understanding of the evolutionary past of the most deadly
      of the human malaria species--P. falciparum.

PMID- 14711088
TI  - Phylogenies, the comparative method and parasite evolutionary ecology.
AB  - A growing number of comparative analyses in the field of parasite evolution and
      ecology have used phylogenetically based comparative methods. However, the
      comparative approach has not been used much by parasitologists. We present the
      rationale for the use of phylogenetic information in comparative studies, and we
      illustrate the use of several phylogenetically based comparative methods with
      case studies in parasite evolutionary ecology. The independent contrasts method
      is the most popular one, but presents some problems for studying co-adaptation
      between host and parasite life traits. The eigenvector method has been recently
      proposed as a new method to estimate and correct for phylogenetic inertia. We
      illustrate this method with an investigation of patterns of helminth parasite
      species richness across mammalian host species. This method seems to perform well
      in situations where host and parasite phylogenies are not perfectly congruent,
      but one might still want to correct for the effects of both. Finally, we present
      a method recently proposed for variation partitioning in a phylogenetic context,
      i.e. the phylogenetically structured environmental variation.

PMID- 14711089
TI  - Recent results in cophylogeny mapping.
AB  - Virtually every problem in biology benefits from consideration within an
      evolutionary frame work. Parasitism has been part of life ever since one organism
      was able to provide an environment for another: questions of parasitology
      naturally lend themselves to consideration of the shared ancient history of
      parasites and hosts. The derivation of that shared history is therefore an area
      of great interest to theoreticians and practitioners alike. The most intuitive
      approach to this is by cophylogeny mapping. Mathematically the problem is that of
      optimally mapping the dependent tree into the independent one, e.g., parasite
      into host or gene tree into organismal phylogeny. This article describes some of
      the recent advances in cophylogenetic simulation, significance testing, and
      theoretical properties of maps. In simulation the author shows that the number of
      ways of mapping the parasite phylogeny into that of the hosts does indeed grow
      exponentially quickly in most cases and shows no close correlation with the
      similarity between the phylogenies, and that under a simple coevolutionary model,
      the range of behaviours of simulated parasite phylogenies is extremely broad and
      would appear to confound efforts to infer model parameters from observed cases.
      In the area of significance testing the author demonstrates that the maximal
      number of inferred codivergence events is not necessarily the best statistic for
      measuring cophylogenetic agreement, and that significance testing by
      randomisation which does not alter the parasite tree substantially biases
      results, and provides a new test to determine whether phylogenetic similarity is
      consistent with preferential host switching.

PMID- 14711090
TI  - Inference of viral evolutionary rates from molecular sequences.
AB  - The processes of mutation and nucleotide substitution contribute to the observed
      variability in virulence, transmission and persistence of viral pathogens. Since
      most viruses evolve many times faster than their human hosts, we are in the
      unusual position of being able to measure these processes directly by comparing
      viral genes that have been isolated and sequenced at different points in time.
      The analysis of such data requires the use of specific statistical methods that
      take into account the shared ancestry of the sequences and the randomness
      inherent in the process of nucleotide substitution. In this paper we describe the
      various statistical methods for estimating evolutionary rates, which can be
      classified into three general approaches: linear regression, maximum likelihood,
      and Bayesian inference. We discuss the advantages and shortcomings of each
      approach and illustrate their use through the analysis of two example viruses;
      human immunodeficiency virus type 1 and dengue virus serotype 4. Reliable
      estimates of viral substitution rates have many important applications in
      population genetics and phylogenetics, including dating evolutionary events and
      divergence times, estimating demographic parameters such as population size and
      generation time, and investigating the effect of natural selection on molecular
      evolution.

PMID- 14711091
TI  - Detecting adaptive molecular evolution: additional tools for the parasitologist.
AB  - It is likely that infectious diseases have shaped the evolution of many
      vertebrates, including humans. The etiological agents of disease continuously
      strive to evade the immune response and the immune response, in turn, seeks to
      change in order to keep pace with the invaders. This 'arms race' may be
      characterized by the selection for new variant hosts and new variant parasites.
      Here we discuss the utility of phylogenetics in detecting adaptive evolution at
      the molecular level and, for illustration, we concentrate on a family of surface
      exposed proteins (the rifins) found in the recently sequenced genome of
      Plasmodium falciparum. We employed phylogeny-based methods in order to
      characterize adaptive evolution in these proteins. We found evidence for adaptive
      evolution in many of the amino acid residues in at least one lineage. These
      results indicate that there has been selection for those strains of P. falciparum
      that contain the new genotypes. These proteins are likely to be of great
      importance for the survival of the parasite. Studies of the interaction of these
      proteins with the antigen-presenting cells of the immune system should lead to a
      better understanding of malarial infection.

PMID- 14711092
TI  - Molecular detection and typing of fungal pathogens.
AB  - A major goal of molecular testing is to develop a cost-effective as well as
      sensitive and specific assay that can detect microbial DNA in clinical samples
      early in the course of disease. Additionally, the ability to analyze the genetic
      relatedness of fungi on a timelier basis using molecular methods will have a
      positive impact on epidemiologic investigating. As technology advances, it seems
      apparent that commercially available molecular assays will become available in
      the near future for the management of patients with suspected fungal infections.

PMID- 14711093
TI  - Recent advances in laboratory procedures for pathogenic mycobacteria.
AB  - Just as tuberculosis has persisted for many centuries as one of most serious and
      deadly infectious diseases in many parts of the world, so has the motivation to
      develop improved laboratory methods for characterizing M. tuberculosis isolates.
      Modern technology has lead to great improvements in mycobacteriology laboratory
      procedures, particularly in detection, identification, epidemiologic strain
      typing, and drug susceptibility testing. Although the usefulness of some of these
      newer methods is under evaluation, many already are showing potential as adjuncts
      to clinical diagnostic procedures.

PMID- 14711094
TI  - Molecular detection of resistance to antituberculous therapy.
AB  - Drug-resistant tuberculosis is becoming increasingly common and represents a
      worldwide threat. Therefore, new approaches for the rapid susceptibility testing
      of Mycobacterium tuberculosis are needed to replace traditional culture-based
      methods. This article presents the genetic background of drug resistance in
      tubercle bacillus, and the methods currently available for genotypic
      susceptibility testing.

PMID- 14711095
TI  - Molecular diagnosis of viral infections of the central nervous system.
AB  - The development of techniques for the amplification of DNA and RNA opened the way
      for the creation of extremely specific, sensitive, and rapid diagnostic tests for
      the detection of viral infections of the central nervous system. Polymerase chain
      reaction (PCR) and reverse transcription PCR diagnostic assays have
      revolutionized the approach to the diagnosis of important viral pathogens--in
      particular, enteroviruses (EVs), herpes viruses, and JC virus (JCV). These
      molecular approaches to diagnosis have led to improvements in clinical outcome
      and patient care. Additionally, their use has permitted a better understanding of
      the natural history and clinical spectrum of the syndromes caused by these
      important human pathogens. This article summarizes the current understanding with
      regard to the available, molecularly based, diagnostic assays for the detection
      of EVs, herpes viruses, and JCV.

PMID- 14711096
TI  - Molecular methods for ehrlichiosis and Lyme disease.
AB  - This article reviews molecular techniques that have been developed and are
      effective in the clinical laboratory for the emerging tick-borne infections,
      ehrlichiosis and Lyme disease.

PMID- 14711097
TI  - Molecular epidemiology in the public health and hospital environments.
AB  - The increasing speed and ease of genomic sequencing coupled with available
      funding to sequence multiple, unrelated strains of the same species will lead
      inevitably to the identification of candidate genes that can be used as molecular
      typing tools (MLST, SLST, microarray approach). However, it is important to note
      that even the most sophisticated typing tool should never replace a full
      epidemiologic investigation in which all available information is taken into
      account. Nevertheless, the typing methods discussed in this article and those yet
      to be developed have significantly improved the quality of health care worldwide.

PMID- 14711098
TI  - Molecular detection of infections associated with neoplasia.
AB  - This article discusses the molecular targets and the methods for identification
      of human papillomavirus and the human gammaherpesviruses, Epstein-Barr virus and
      human herpesvirus type 8.

PMID- 14711099
TI  - Detection of antiretroviral resistance in HIV-1.
AB  - Resistance testing should be readily available to every clinician who specializes
      in HIV/AIDS. Based in part on requests we receive in our laboratory, we believe
      that the use of resistance testing is expanding. However, selecting an initial
      antiretroviral treatment regimen or changing a failing one according to the test
      results is complex and inexact and requires knowledgeable interpretation to
      maximize the clinical benefit. Future studies about viral fitness and other
      viral, host, and pharmacologic factors responsible for disease progression likely
      will facilitate more precise application of resistance testing to the clinical
      setting.

PMID- 14711100
TI  - MRI during pregnancy.
AB  - The use of ultrasonography (USG) during pregnancy provides a tremendous amount of
      valuable information about fetal and maternal well-being. However, in some cases
      the image quality may be poor due to maternal fat tissue, fetal position, or some
      other reason. Magnetic resonance imaging (MRI) can provide clear images from
      multiple angles without X-ray exposure. We believe that it is important to
      evaluate the usefulness of MRI for diagnostic purposes during pregnancy. While
      MRI can provide different information to what can be obtained from USG, it is not
      always superior to USG. The clinical indications for MRI during pregnancy are
      limited but well defined. Fetal MRI is a valuable complement to USG especially in
      the further evaluation of problems first detected by USG. When MRI is performed,
      we must consider its purpose and accordingly determine the appropriate procedure
      to provide the most precise and useful diagnostic information.

PMID- 14711101
TI  - Magnetic resonance imaging and ultrasound in the assessment of the fetal central
      nervous system.
AB  - Ultrasound is the screening modality of choice for evaluation of the fetal
      central nervous system (CNS). However, in cases of difficult diagnosis further
      fetal investigation is desirable. Due to ultrafast magnetic resonance imaging
      (MRI) techniques artifacts from fetal motions are minimized. MRI involves no
      exposure to radiation and hence appears to be safe. Due to the better soft tissue
      contrast, additional investigation by MRI may extend the sonographic diagnosis of
      fetal CNS-anomalies. Ultrasound and MRI are complementary imaging methods in the
      evaluation of the fetal CNS. The most important indications for ultrasound are
      screening for CNS anomalies and serial assessment of the dynamic of the disorder.
      The most important indications for fetal MRI are the "second opinion" and
      investigation by fetal MRI instead of postpartum MRI (especially in cases of
      planned postpartum intervention). In this article the indications and limitations
      of ultrasound and magnetic resonance imaging in the evaluation of the fetal CNS
      are discussed.

PMID- 14711102
TI  - Maternal erythrocyte malondialdehyde level in preeclampsia prediction: a
      longitudinal study.
AB  - We aimed to determine the value of maternal erythrocyte malondialdehyde levels in
      the prediction of preeclampsia. 110 healthy women were included in this
      prospective study. Maternal erythrocyte malondialdehyde levels were measured at
      each trimester of pregnancy (10-14, 20-25 and 30-35 gestational weeks). On follow
      up, patients were assigned to two groups as normotensive women and preeclamptic
      patients. Preeclampsia had developed in eight (8.9%) of the 90 pregnant women who
      completed the study. Preeclamptic patients were diagnosed between 36 and 39
      gestational weeks (36.8 +/- 1.0 weeks). Malondialdehyde levels of preeclamptic
      patients increased significantly in the third trimester (p < 0.05), while there
      was no difference between values of malondialdehyde in the first and second
      trimester. Malondialdehyde levels were significantly higher in the patients who
      developed preeclampsia than in those who did not in the third trimester (p <
      0.05). With the use of the receiver operating characteristics (ROC) 35.98 nmol
      malondialdehyde/gm hemoglobin was found to be a cut-off value predictive for the
      development of preeclampsia in the third trimester. However, cut-off values in
      the first and second trimesters could not be found. The sensitivity, specificity,
      positive and negative predictive values were 89, 75, 29 and 98%, respectively.
      Preeclampsia risk was found to increase nearly 24 times in values above 35.98
      nmol malondialdehyde/ gm hemoglobin. Our results showed that maternal erythrocyte
      malondialdehyde could predict patients within a few weeks prior to onset of
      clinical symptoms of preeclampsia in the third trimester. There is no evidence of
      enhanced early lipid peroxidation in pregnancies with late onset preeclampsia.

PMID- 14711103
TI  - Effect of fetal macrosomia on human placental glucose transport and utilization
      in insulin-treated gestational diabetes.
AB  - The aim of this study was to compare glucose transport and utilization in human
      placentae from pregnancies affected by insulin-treated GDM with and without
      macrosomia, and from non-diabetic control pregnancies. Placental lobules were
      perfused for 4 h. Maternal D-glucose concentration was 4, 8, 16, or 24 mM while
      the fetal D-glucose was maintained at 3mM. 14C-D-glucose and 3H-L-glucose were
      infused into the maternal circulation. Radioactivity, D-glucose and L-lactate
      levels were measured in the fetal and maternal effluent perfusates. Glucose
      uptake from the maternal perfusate, and transfer to the fetal effluent were not
      significantly different between groups. Insulin-treated GDM group without
      macrosomia had reduced glucose utilization compared to the control group while
      the insulin-treated GDM group with macrosomia did not. Lactate release into the
      fetal effluent was significantly reduced in both insulin-treated GDM groups
      compared to the control group. In conclusion, placental glucose utilization is
      different between insulin-treated GDM placentae with and without fetal
      macrosomia.

PMID- 14711104
TI  - Association between maternal-fetal Doppler velocimetry and fetal lung maturity.
AB  - AIMS: To correlate maternal-fetal Doppler velocimetry parameters to indices of
      fetal lung maturity (FLM). METHODS: Fifty-five consecutive third trimester
      pregnancies in which a pulsed-wave Doppler study, including uterine resistance
      index (Ut RI), umbilical artery pulsatility index (UA PI), middle cerebral artery
      pulsatility index (MCA PI) and the UA/MCA ratio was performed within 24 hours
      before amniocentesis and within a week from birth. FLM was determined by amniotic
      fluid lamellar bodies count (LBs). RESULTS: A positive correlation between MCA PI
      and LBs (p < 0.007, r = 0.44) was found. MCA PI showed a trend to lower values in
      fetuses that developed RDS at birth (1.3 +/- 0.5 vs. 1.7 +/- 0.4, NS). LBs
      significantly decreased as Ut RI increased (O.R.: 0.98, C.I. 0.97-0.99, p <
      0.05). A mean Ut RI > 0.64 was correlated to delayed FLM (LBs < 20,000/microl;
      sensitivity: 90.9%, specificity: 90.3%; positive predictive value: 76.9%,
      negative predictive value: 96.6%). COMMENT: In third trimester pregnancies
      abnormal uterine artery waveforms may be associated to a delayed FLM, as
      expressed by decreased amniotic fluid LBs.

PMID- 14711105
TI  - Does the thrifty phenotype result from chronic glutamate intoxication? A
      hypothesis.
AB  - The thrifty phenotype hypothesis proposes that the epidemiological associations
      between poor fetal and infant growth and the subsequent development of the
      metabolic syndrome, result from the effects of poor nutrition in early life. The
      present review however, considers an opposite explanation. We hypothesize that
      fetal over-nutrition plays a major role in the development of the metabolic
      syndrome. We found evidence that the thrifty phenotype may be the consequence of
      fetal hyperglutamatemia. Maternal glutamate (GLU) reaches the fetal circulation,
      as part of the materno-fetal glutamine-glutamate exchange. Glutamine is absorbed
      from the maternal circulation, and deaminated for nitrogen utilization, resulting
      in a fetal production of GLU. GLU is extracted as it returns to the placenta.
      When the umbilical plasma flow is low, GLU may be trapped in the fetal
      circulation, and reaches neurotoxic levels. Administering GLU to newborn rodents
      completely destructs arcuate nucleus neurons, and results in permanently elevated
      plasma leptin levels that fail to adequately counter-regulate food intake.
      Chronic fetal exposure to elevated levels of GLU may be caused by chronic
      maternal over-nutrition or by reduced umbilical plasma flow. We strongly suggest
      abandoing the flavoring agent monosodium glutamate and reconsidering the
      recommended daily allowances of protein and amino acids during pregnancy.

PMID- 14711106
TI  - Fetal hand movements and facial expression in normal pregnancy studied by four
      dimensional sonography.
AB  - AIM: To evaluate the developmental pattern of fetal hand movements and facial
      activity and expression during the second and third trimester of pregnancy by
      four-dimensional ultrasound (4D-US). SUBJECTS AND METHODS: A total of 25 fetuses
      in uncomplicated pregnancies were analyzed; 15 fetuses at 13 to 16 weeks and 10
      fetuses at 30 to 33 weeks of gestation were studied with abdominal 4D-US. After
      standard assessment in two dimensional (2D) real-time B mode, a 4D mode was
      switched on. Further examination lasted a maximum of 15 minutes. RESULTS:
      Isolated hand movement and subtypes of hand movements were easily recognized by
      4D-US. The sub-types of hand to head movement are: hand to head, hand to mouth,
      hand near mouth, hand to face, hand near face, hand to eye and hand to ear. All
      subtypes of hand to head movement can be seen from 13 weeks of gestation, with
      fluctuating incidence. Facial activities and different forms of expression are
      easily recognized by 4D-US. Among these, two types can be easily differentiated:
      smiling and scowling. CONCLUSIONS: 4D-US is superior over real-time two
      dimensional ultrasound (2D-US) for qualitative, but inferior for quantitative
      analysis of hand movements. Thus 4D-US makes it possible to determine exactly the
      direction of the fetal hand, but the exact number of each type of hand movements
      can still not be determined. 4D-US is superior over two- and three-dimensional
      sonography in the evaluation of complex facial activity and expression. Among
      facial activities observed by 4D-US, simultaneous eyelid and mouthing movements
      dominate between 30 and 33 weeks of gestation. Pure mouth movements such as mouth
      opening, tongue expulsion, yawning and pouting are present, but at a
      significantly lower incidence. Facial expressions such as smiling and scowling
      can be precisely observed using 4D-US.

PMID- 14711107
TI  - Stable microbubble test and click test to predict respiratory distress syndrome
      in preterm infants not requiring ventilation at birth.
AB  - AIMS: To determine the usefulness of the stable microbubble test (SMT) and of the
      click test (CT) on gastric aspirates obtained soon after birth to predict
      respiratory distress syndrome (RDS) in preterm babies not requiring ventilation
      at birth. PATIENTS AND METHODS: The study was carried out with a cohort between
      24 and 34 weeks of gestational age. Gastric secretions were collected before 1
      hour of life and frozen for further analysis. RESULTS: 110 neonates were studied.
      For a cut-off value 10 microbubbles/mm2 (mb/mm2) the sensitivity and specificity
      to predict RDS were 73.9 % and 92%, respectively, in the SMT. The best SMT cut
      off point to predict RDS was < or = 15 mb/mm2 (sensitivity = 82.6% specificity =
      85.1%) if equal weight was given to false-positive and false-negative results. CT
      (104 samples) showed a sensitivity of 100% and a specificity of 45.1% to predict
      RDS. The overall accuracy of the SMT was better than the overall accuracy of the
      CT (87.5% vs. 64.4%; p < 0.001) to predict RDS. CONCLUSIONS: The SMT is more
      accurate than the CT to predict RDS in infants below 35 weeks of gestational age
      and may be helpful to select patients to receive surfactant.

PMID- 14711108
TI  - Staphylococcal scalded skin syndrome in two very low birth weight infants.
AB  - Two premature infants with very low birth weight were diagnosed with
      staphylococcal scalded skin syndrome (SSSS) during hospitalization in the
      neonatal intensive care unit. This syndrome which is rare in premature infants,
      is characterized by blistering and superficial desquamation of the skin and is
      caused by two epidermolytic toxins (ETA and ETB) produced by Staphylococcus
      aureus. Staphylococcal scalded skin syndrome usually occurs in young children
      probably because of inefficient clearance of the epidermolytic toxins from the
      bloodstream, which causes dysfunction of cell adhesion in the superficial
      epidermis. Early diagnosis and early treatment with parenterally administered
      beta-lactamase resistant penicillins are important to prevent life threatening
      complications of this syndrome.

PMID- 14711109
TI  - Umbilical glutathione levels are higher after vaginal birth than after cesarean
      section.
AB  - Glutathione plays an important role in quenching reactive oxygen species,
      resulting in oxidation of glutathione, which in times of prolonged oxidative
      stress may be excreted from the erythrocyte. We investigated arterial and venous
      umbilical cord levels of glutathione in neonates born by vaginal delivery (n =
      140) or cesarean section (n = 38). In a subset of neonates who were delivered
      vaginally maternal levels were assessed in parallel (n = 14). Median (5th-95th
      percentile) glutathione levels in venous and arterial umbilical samples were
      higher after vaginal delivery as compared to cesarean section, 2.7 (0.9-7.3)
      versus 2.0 (0.6-11.5; P < 0.03) and 3.5 (0.6-22.7) versus 2.3 (0.7-24.3)
      micromol/L (P < 0.02), respectively. Maternal glutathione levels were higher, 7.8
      (4.3-10.6) micromol/L, than corresponding venous (P < 0.001) or arterial (P <
      0.02) umbilical levels. These results suggest that vaginal delivery is associated
      with more oxidative stress than delivery by cesarean section.

PMID- 14711110
TI  - Gastrointestinal contrast studies in high-risk neonates with suspected
      necrotising enterocolitis--a note of caution.
AB  - Upper gastrointestinal contrast studies are frequently performed in neonates to
      rule out conditions such as malrotation. Low osmolality water-soluble (LOWS)
      contrast media are currently considered safe for use in neonates. The clinical
      course of a neonate with suspected necrotising enterocolitis, who deteriorated
      significantly due to peritonitis following contrast study with LOWS, is reported.
      The possibility that LOWS contrast media may not always be safe in high-risk
      neonates is raised.

PMID- 14711111
TI  - Fatal intracranial hemorrhage in a pregnant patient with autoimmune
      thrombocytopenic purpura.
AB  - Thrombocytopenia in pregnancy is a frequent cause of hematological consultation.
      Autoimmune thrombocytopenic purpura results from platelet destruction due to
      autoantibodies. Spontaneous intracranial hemorrhage is a rare but devastating
      complication of these patients. We present a fatal case of intracranial
      hemorrhage in a 18 week pregnant woman diagnosed with autoimmune
      thrombocytopenia. The clinical course and treatment of this unusual clinical
      complication is discussed in relation to the world literature.

PMID- 14711112
TI  - Pregnancy complicated with pure red cell aplasia: a case report.
AB  - A 31-year-old Japanese pregnant woman had no remarkable previous medical and
      family histories except for artificial abortion in 1993. A full-term normal
      infant was subsequently delivered in 1998. In this pregnancy, she began to
      experience general fatigability with a hemoglobin concentration of 8.5 g/dl at 19
      weeks of gestation. Although she had been treated with intravenous iron, the
      hemoglobin decreased to 6.0 g/dl. She was referred to our hospital at 34 weeks of
      gestation. The laboratory data were as follows on this admission; hemoglobin 5.1
      g/dl, RBC 128 x 10(4)/l, reticulocytes 1.1%, WBC 7.1 x 10(9)/l, platelet count
      229 x 10(9)/l, folic acid 5.6 ng/ml, serum vitamin B12 200 pg/ml, ferritin 184
      ng/ml, parvovirus B19 (-). A bone marrow aspiration revealed normal
      granulopoiesis and megakaryocytes, but almost complete absence of erythropoietic
      precursors. A diagnosis of pure red cell aplasia was made due to these findings.
      Treatment with prednisone (50 mg/day) and blood transfusion was started before
      delivery. She was delivered transvaginally at 37 weeks of gestation. The neonate
      was a normal female infant without anemia (hemoglobin 17.9 g/dl) and the 1 minute
      Apgar score was 8. Her hemoglobin level rose to 12.1 g/dl spontaneously two weeks
      after delivery.

PMID- 14711113
TI  - Mucopolysaccharidosis type VII as a cause of recurrent non-immune hydrops
      fetalis.
AB  - BACKGROUND: Mucopolysaccharidosis type VII (MPS VII) is a rare lysosomal storage
      disease first described by Sly in 1973. There are fewer than thirty reported
      cases world wide. This extremely rare disorder can present in-utero as hydrops
      fetalis and has a high recurrence rate. However, prenatal diagnosis in the
      absence of a previously affected child, has not been reported to date. CASE: This
      is a case of a non-consanguineous couple, with no history of a previously
      affected child with MPS VII, presenting with recurrent hydrops fetalis. During
      the work-up, the affected fetus was diagnosed in-utero with beta-glucuronidase
      deficiency which is pathognomonic for MPS VII. Prenatal diagnosis was then
      performed in subsequent pregnancies. CONCLUSION: The importance of an extensive
      and thorough investigation for the etiology of hydrops fetalis is discussed.

PMID- 14711114
TI  - Higher risk of persistent pulmonary hypertension of the newborn after cesarean.
AB  - Authors suggest that high incidence of persistence pulmonary hypertension among
      neonates delivered by elective cesarean is related to lower levels of circulating
      norepinephrine in neonates after cesarean section than after vaginal delivery.

PMID- 14711115
TI  - Dynamics of endosomal sorting.
AB  - The endocytic pathway receives cargo from the cell surface via endocytosis,
      biosynthetic cargo from the late Golgi complex, and various molecules from the
      cytoplasm via autophagy. This review focuses on the dynamics of the endocytic
      pathway in relationship to these processes and covers new information about the
      sorting events and molecular complexes involved. The following areas are
      discussed: dynamics at the plasma membrane, sorting within early endosomes and
      recycling to the cell surface, the role of the cytoskeleton, transport to late
      endosomes and sorting into multivesicular bodies, anterograde and retrograde
      Golgi transport, as well as the autophagic pathway.

PMID- 14711116
TI  - Role of rab proteins in epithelial membrane traffic.
AB  - Small GTPase rab proteins play an important role in various aspects of membrane
      traffic, including cargo selection, vesicle budding, vesicle motility, tethering,
      docking, and fusion. Recent data suggest also that rabs, and their divalent
      effector proteins, organize organelle subdomains and as such may define
      functional organelle identity. Most rabs are ubiquitously expressed. However,
      some rabs are preferentially expressed in epithelial cells where they appear
      intimately associated with the epithelial-specific transcytotic pathway and/or
      tight junctions. This review discusses the role of rabs in epithelial membrane
      transport.

PMID- 14711117
TI  - Mechanisms of insulator function in gene regulation and genomic imprinting.
AB  - Correct temporal and spatial patterns of gene expression are required to
      establish unique cell types. Several levels of genome organization are involved
      in achieving this intricate regulatory feat. Insulators are elements that
      modulate interactions between other cis-acting sequences and separate chromatin
      domains with distinct condensation states. Thus, they are proposed to play an
      important role in the partitioning of the genome into discrete realms of
      expression. This review focuses on the roles that insulators have in vivo and
      reviews models of insulator mechanisms in the light of current understanding of
      gene regulation.

PMID- 14711119
TI  - Molecular aspects of membrane trafficking in paramecium.
AB  - Results achieved in the molecular biology of Paramecium have shed new light on
      its elaborate membrane trafficking system. Paramecium disposes not only of the
      standard routes (endoplasmic reticulum --> Golgi --> lysosomes or secretory
      vesicles; endo- and phagosomes --> lysosomes/digesting vacuoles), but also of
      some unique features, e.g. and elaborate phagocytic route with the cytoproct and
      membrane recycling to the cytopharynx, as well as the osmoregulatory system with
      multiple membrane fusion sites. Exocytosis sites for trichocysts (dense-core
      secretory vesicles), parasomal sacs (coated pits), and terminal cisternae (early
      endosomes) display additional regularly arranged predetermined fusion/fission
      sites, which now can be discussed on a molecular basis. Considering the regular,
      repetitive arrangements of membrane components, availability of mutants for
      complementation studies, sensitivity to gene silencing, and so on, Paramecium
      continues to be a valuable model system for analyzing membrane interactions. This
      review intends to set a new baseline for ongoing work along these lines.

PMID- 14711118
TI  - Unresolved issues in mammalian fertilization.
AB  - This review considers the role of the sperm in fertilization, addressing areas of
      misunderstanding and unfounded assumptions and taking particular advantage of the
      large body of data resulting from work with rodent species in vitro. Considerable
      attention is given to the appropriate use and interpretation of assays for
      capacitation, acrosomal exocytosis, hyperactivation, and sperm protein
      phosphorylation, as well as tests for sperm-zona and sperm-oocyte membrane
      interactions. The lack of general agreement on the means of sperm adhesion to and
      penetration of the zona pellucida is addressed, and the need for new approaches
      to this problem is pointed out. Some molecular advances in our understanding of
      specific steps in the process of fertilization are discussed in the context of
      intact cell-matrix and cell-cell interaction. This review should provide
      practical information for researchers just beginning the study of fertilization
      and interesting but not widely known observations to stimulate new ideas in
      experienced scientists.

PMID- 14711120
TI  - Organization, developmental dynamics, and evolution of plastid nucleoids.
AB  - The plastid is a semiautonomous organelle essential in photosynthesis and other
      metabolic activities of plants and algae. Plastid DNA is organized into the
      nucleoid with various proteins and RNA, and the nucleoid is subject to dynamic
      changes during the development of plant cells. Characterization of the major DNA
      binding proteins of nucleoids revealed essential differences in the two lineages
      of photosynthetic eukaryotes, namely nucleoids of green plants contain sulfite
      reductase as a major DNA-binding protein that represses the genomic activity,
      whereas the prokaryotic DNA-binding protein HU is abundant in plastid nucleoids
      of the rhodophyte lineage. In addition, current knowledge on DNA-binding
      proteins, as well as the replication and transcription systems of plastids, is
      reviewed from comparative and evolutionary points of view. A revised hypothesis
      on the discontinuous evolution of plastid genomic machinery is presented: despite
      the cyanobacterial origin of plastids, the genomic machinery of the plastid
      genome is fundamentally different from its counterpart in cyanobacteria.

PMID- 14711121
TI  - Fundamental principles of evidence-based medicine applied to mental health care.
AB  - This article discusses the fundamental principles of evidence-based medicine:
      using the best available evidence, individualizing the evidence, attending to
      patient preferences, and expanding clinical expertise. These principles have
      important implications for the adoption of evidence-based practices in mental
      health care.

PMID- 14711122
TI  - Finding and evaluating the evidence: a critical step in evidence-based medicine.
AB  - Practitioners of evidence-based medicine are expected to review the evidence for
      treatment effectiveness with their patients as part of the shared decision-making
      process. This requires practitioners to know the evidence or to know how to find
      and evaluate it. To find the evidence, the practitioner must craft the search
      question by considering the domains of population, intervention, and outcome as a
      means to individualize the search for each patient. To evaluate the evidence, the
      practitioner needs to understand the strengths and weaknesses of various types of
      scientific evidence. Most practitioners will consult EBP guidelines first. If
      guidelines do not answer the search question, the practitioner will turn to
      systematic reviews, ensuring that their methods of selection and evaluation are
      explicit and appropriate. Searching the scientific literature for single studies
      is also possible, but evaluating primary sources is more difficult. Given the
      constraints of time and expertise, the authors anticipate that computerized
      expert systems, based on current evidence, will become increasingly prominent.

PMID- 14711123
TI  - The role of information technology in evidenced-based practice.
AB  - Clinical Computing is a natural tool for evidence-based practice. Automated self
      report produces accurate clinical assessments both in research and clinical
      settings, thus assuring that patients in each satisfy the same symptom criteria.
      The Electronic Medical Record (EMR) eventually will form a real-time Information
      bridge between research and clinical settings. Despite substantial literature
      demonstrating the efficacy of clinical computing in psychiatric care and
      research, however, psychiatrists have been slow to adopt computers, and research
      has dwindled. The steady emergence of system-wide EMRs, will spark a resurgence.

PMID- 14711124
TI  - Training in evidence-based practice.
AB  - Controversy surrounds the concept of EBP. Many individuals question whether
      research is capable of guiding decisions about diagnosis and treatment, or
      whether it simply gives oversimplified answers to highly complex questions about
      human behavior. These concerns aside, it is hard to envision a future in which
      consumers and payers do not demand that the health professions ground their
      interventions in an evidence base. It is sobering to recognize that training in
      EBP has been far from the norm in the various behavioral health disciplines. This
      is just one aspect of a much larger crisis in behavioral health workforce
      education. Graduate and residency programs have not kept pace with many of the
      changes in behavioral health care delivery over the past decade. The field
      continues to use continuing education strategies that are ineffective, and little
      training is offered to the paraprofessional and bachelor-prepared staff members
      who comprise a large segment of the workforce in public sector and inpatient
      settings. Broad strategies are needed to overcome the lethargy in behavioral
      health education and training programs to make them more relevant to contemporary
      clinical practice. Incorporating evidence-based approaches to treatment is one
      critical element of needed reforms. General medicine has laid a foundation that
      can be built on for teaching the process of EBP. Psychiatry and psychology have
      taken the lead in identifying those interventions to be taught that are evidence
      based or empirically supported. Research on continuing education and adult
      learning illuminates the educational strategies that are likely effective in
      teaching evidence-based interventions and an evidence-based process of care.
      Additionally, the research on changing provider behavior shows the importance of
      ensuring practice environments that support and reinforce, rather than thwart,
      the practice of evidence-based treatment. There are many resources to draw on but
      the task facing educators is substantial.

PMID- 14711125
TI  - Consumers and families as partners in implementing evidence-based practice.
AB  - Evidence-based practices represent an extremely important advance in the mental
      health system, and NAMI continues its support of efforts to develop and implement
      these interventions. Moving forward, the authors envision consumers and family
      members playing a much greater role in developing and promulgating EBP.
      Individually and corporately, consumers can: facilitate research that will
      expedite equitable implementation of existing and new EBPs; play a significant
      role in providing services; play a lead role in promoting policies that support
      EBP implementation through the development and use of advocacy toolkits;
      influence provider adaptation of EBP through the broad development and testing of
      resources that urge EBP consumerism; and, advance through the monitoring of EBP.
      These consumer-led activities generally have been relegated to a lower level of
      importance in the current research, policy, and funding environment leading to
      poorly developed partnerships and "buy in" from the consumer community. It is
      important that the level of importance of these activities and the role of
      consumers and families be rethought. Further advancement of EBP will require
      implementing a three-track program of research, including a much greater focus on
      action research and the involvement of consumers as research and evaluation
      partners. This is the fastest and most effective way to achieve breakthrough
      results in practices for treating people with serious mental illnesses and to
      address the serious and growing problem of racial and cultural disparities and
      the disconnect that causes between those individuals and the means to their
      recovery. The hope of consumers and families rest on the ability to initiate
      action now.

PMID- 14711126
TI  - Strategies for leading the implementation of evidence-based practices.
AB  - Many mental health authority and program administrators would like to implement
      behavioral health practices that have been demonstrated to be effective. Leading
      practice implementation involves promoting behavior change in health care
      providers. Reviews of the general medical literature on practice change conclude
      that education alone has little impact on practitioner behavior and that
      intensive, multifaceted interventions that attend to local circumstances have the
      greatest likelihood of affecting change. This article briefly reviews the
      literature on health care practice change and offers some strategy suggestions
      for administrators who are leading evidence-based practice implementation
      initiatives.

PMID- 14711127
TI  - Public policy and evidence-based practice.
AB  - The time has come to add to the body of EBP implementation knowledge at multiple
      levels, including knowledge about policy, program priorities, clinician practice,
      consumer adherence, and family member support. Implementation at the policy
      level, however, is primary and paramount. The national initiative supporting EBP
      implementation is one of the most important innovations on the mental health
      horizon. It will serve as the testing ground for what can be learned about
      bridging the gap between science and service. This important initiative will not
      go far if it is not supported by mental health policies--at state and federal
      levels--that create the organizational and financial incentives to implement
      EBPs. In addition, it will be a time-limited activity if it also does not yield
      lessons about how to adapt to new evidence and on-going systemic changes.
      Organizations must be flexible and able to learn and adapt. The promise of
      decades of research must be realized in practice. There is an opportunity to
      combine quality improvement with accountability through performance measurement
      and the implementation of effective new services and treatments. The Surgeon
      General simultaneously identified this research's promise and documented its
      shortcomings. His report outlines courses of action for policymakers that should
      guide clinicians away from service disparities and toward the implementation of
      EBP.

PMID- 14711128
TI  - Evidence-based practices: setting the context and responding to concerns.
AB  - After nearly 20 years of progress in general medicine, the evidence-based
      practice movement is becoming the central theme for mental health care reform in
      the first decade of 2000. Several leaders in the movement met to discuss concerns
      raised by six stakeholder groups: consumers, family members, practitioners,
      administrators, policy makers, and researchers. Recurrent themes relate to
      concerns regarding the limits of science, diversion of funding from valued
      practices, increased costs, feasibility, prior investments in other practices,
      and shifts in power and control. The authors recommend that all stakeholder
      groups be involved in further dialog and planning to ensure that practices emerge
      that represent the integration of the best research evidence with clinical
      expertise and consumer values.

PMID- 14711129
TI  - Evidence-based treatment for schizophrenia.
AB  - Taken together, the research on what treatments help people with schizophrenia
      point to the value of treatment programs that combine medications with a range of
      psychosocial services. Provision of such packages of services likely reduces the
      need for crisis-oriented care hospitalizations and emergency room visits and
      enables greater recovery. For most people with schizophrenia, the combination of
      psychopharmacological and psychosocial interventions improves outcomes. Several
      psychosocial treatments have demonstrated efficacy. These include family
      intervention, supported employment, assertive community treatment, skills
      training, and CBT. In the same way that psychopharmacologic management must be
      tailored individually to the needs and preferences of the patient, so too should
      the selection of psychosocial treatments. At the very least, all people with
      schizophrenia should be provided with education about their illness. Beyond
      illness education, all of the recommended psychosocial interventions would be
      used rarely during any one phase of illness for an individual. Some psychosocial
      treatments share treatment components, and patients have different clinical and
      social needs at different points in their illness course. Knowledge regarding how
      best to combine treatments to optimize outcomes is scarce.

PMID- 14711130
TI  - Children and evidence-based practice.
AB  - Issues and challenges related to reducing the gap between child mental health
      research and practice are not minor. As the field continues to mature, energized
      by the challenges to develop treatment in more innovative ways and to disseminate
      EBP, the potential for improving child mental health is strong.

PMID- 14711131
TI  - Evidence-based practices in geriatric mental health care: an overview of
      systematic reviews and meta-analyses.
AB  - At least 20% of people over the age of 65 suffer from mental disorders. It is
      anticipated that the number of older Americans with psychiatric disorders will
      double over the next 30 years. There is, however, substantial unmet need. The
      recent Surgeon General's Report on Mental Health, a Report on Mental Health from
      the Administration on Aging, and an expert consensus statement underscore the
      need to plan for the challenge of providing services for elderly people with
      major mental disorders. Among the greatest challenges is the expertise gap that
      affects clinicians practicing in routine clinical settings. This gap reflects
      inadequate training in geriatrics and a failure to incorporate contemporary
      clinical research findings and known evidence-based practices (EBPs) into usual
      care. This article provides an overview of the emerging evidence-base supporting
      the efficacy of empirically-validated geriatric mental health interventions for
      major geriatric mental health disorders, including systematic EBP reviews, meta
      analytic studies, and expert consensus statements. Cautions and limitations
      regarding the reliance on randomized, controlled trials, meta-analyses, and
      systematic reviews also are presented.

PMID- 14711133
TI  - The future of evidence-based practices in mental health care.
AB  - The values and recommendations discussed here are featured prominently in the
      final report of the President's New Freedom Commission on Mental Health. It is
      the author's hope that these recommendations will be implemented thoughtfully and
      thoroughly. If so, the benefits of EBP can be realized by individuals who
      experience mental disorders, their families and friends, and the broader society.

PMID- 14711134
TI  - Hypothesis: Superoxide scavengers or superoxide dismutase may potentiate the
      therapeutic efficacy of contact dermatitis against alopecia areata.

PMID- 14711132
TI  - Evidence-based practices for substance use disorders.
AB  - There are inherent complexities in evaluating EBPs for substance use disorders:
      the heterogeneity of the disorder itself, the variability in people who suffer
      from them, the range of settings in which services are provided, and multiple
      lines of research development. This article outlined four models for evaluating
      the evidence for interventions for substance use disorders, and presented brief
      descriptions of pharmacological, behavioral/psychosocial, and treatment services
      that have a clearly defined intervention (chemical agent or manual-guided
      therapy) and a documented record of objective evaluation. Although substantial
      work is underway to evaluate effectiveness in the real world, clinicians and
      individuals with substance use disorders and their families should be cognizant
      of the burgeoning array of effective treatment alternatives that are available.

PMID- 14711135
TI  - One score and ten PDRs ago: the transformation of medical practice.

PMID- 14711136
TI  - Beware confusing micrograms and milligrams.

PMID- 14711137
TI  - Tissue fillers.

PMID- 14711138
TI  - The rounded Siegel scalpel handle: a better instrument for curved incisions.

PMID- 14711139
TI  - A possible role for non-ablative radiofrequency in the treatment of rosacea.

PMID- 14711140
TI  - Remittive effects of intramuscular alefacept in psoriasis.
AB  - Alefacept is the first biologic agent approved for the treatment of chronic
      plaque psoriasis in the United States. Alefacept, administered intravenously
      (i.v.) or intramuscularly (i.m.), was found to be well tolerated, safe, and
      efficacious in two pivotal phase 3 studies in patients with moderate to severe
      psoriasis. Treatment with i.v. alefacept was associated with a median duration of
      off-treatment response of 216 days (approximately 7 months). In a follow-up
      extension study to the phase 3 i.m. study, duration of therapeutic response was
      also examined. Patients who achieved a > or = 75% reduction in baseline Psoriasis
      Area and Severity Index (PASI 75) with the first course of alefacept 15 mg i.m.
      in the phase 3 study maintained a PASI 50 for a median duration of 209 days. In
      addition, the extension study demonstrated that a second course of i.m. alefacept
      is safe and well tolerated in patients with psoriasis.

PMID- 14711141
TI  - Short incubation PDT versus 5-FU in treating actinic keratoses.
AB  - The efficacy of photodynamic therapy (PDT) using broad area treatment with 5
      aminolevulinic acid (ALA) has not been compared to topical 5-fluorouracil (5-FU)
      in the treatment of actinic keratoses (AK). The purpose of this study was to
      compare the efficacy and tolerability of PDT using short incubation time, broad
      area treatment with ALA plus activation with either blue light or laser light to
      topical 5-FU in the treatment of AK of the face and scalp. Thirty-six subjects
      with AK of either the face or scalp were randomized to receive either application
      of ALA for 1 hour followed by activation with blue light or pulsed dye laser or
      topical 5-FU. Efficacy was evaluated by grading AK lesions and photoaging signs.
      Tolerability was assessed by scoring crusting/erosions, erythema and
      stinging/burning. Treatment with PDT using ALA plus blue light was as effective
      as topical 5-FU in clearing AK. PDT using ALA plus laser light was the least
      effective treatment. All treatments made improvements in the signs of photoaging.
      Both PDT treatments were better tolerated than 5-FU. In conclusion, broad area
      PDT treatment with ALA plus activation with blue light appears to be as effective
      as 5-FU in the treatment of AK. ALA plus laser light is somewhat less effective
      than the above therapies. Efficacy could likely be improved with further study of
      laser parameters and incubation times.

PMID- 14711142
TI  - Photodynamic therapy for molluscum contagiosum infection in HIV-coinfected
      patients: review of 6 patients.
AB  - Molluscum contagiosum, a viral disease of the skin, manifests as a smooth
      surfaced, firm, and spherical papule with umbilication of the vertex. It commonly
      presents as multiple lesions, which may be extensive in immunocompromised
      patients, and may mimic cutaneous tumors in HIV co-infected patients. Infection
      usually persists for 6 months to 5 years before resolving naturally. Among immune
      impaired persons with HIV infection is generally more persistent. To date, single
      and combination therapies for such patients have been unsatisfactory. Recent
      observations from a dermatology practice in which 6 patients with HIV and
      molluscum contagiosum were treated with 5-aminolevulinic acid (Levulan Kerastick)
      in conjunction with photodynamic therapy suggest clinical benefits; i.e.,
      substantial reduction in lesional count and severity. Additional research is
      mandated.

PMID- 14711143
TI  - Compatibility of desoximetasone and tacrolimus.
AB  - The physical and chemical compatibility of desoximetasone ointment 0.25% and
      tacrolimus ointment 0.1%, both widely used to treat atopic dermatitis, were
      determined. A 1:1 (w/w) mixture of desoximetasone ointment 0.25% (Topicort, Taro
      Pharmaceuticals USA, Inc.) and tacrolimus ointment 0.1% (Protopic, Fujisawa
      Healthcare, Inc.) were prepared and stored under three different
      temperature/relative humidity conditions: 25 degrees C/60% RH; 30 degrees C/60%
      RH; and 40 degrees C/75% RH. Unmixed ointments stored under the same temperature
      and humidity conditions as the mixture served as controls. Samples were evaluated
      at days 1, 2, 7, 14, and 28 for color, degree of physical separation, and
      chemical stability via reverse-phase high performance liquid chromatography.
      Ranges of relative recovery for each active ingredient for all storage conditions
      ((% Mixture/% Control) x 100) were 89.6-109.3% for tacrolimus and 99.0-103.4% for
      desoximetasone. No significant difference in physical appearance or
      chromatographic profile between the mixture and controls was observed. Therefore,
      we conclude that desoximetasone ointment 0.25% (Topicort) and tacrolimus ointment
      0.1% (Protopic) are physically and chemically compatible up to four weeks when
      mixed in a ratio of 1:1 (w/w).

PMID- 14711144
TI  - Effect of PTU on IL-12 and IL-10 in psoriasis.
AB  - Propylthiouracil (PTU), an antithyroid thioureylene with immunomodulatory
      properties, has been shown to be effective in the therapy of patients with plaque
      psoriasis. The mechanism of action of antithyroid thioureylenes in psoriasis
      remains unknown. Propylthiouracil is a commonly used agent in the treatment of
      patients with Graves' hyperthyroidism, a condition associated with elevated
      levels of interleukin-12 (IL-12), which fall significantly after propylthiouracil
      treatment. IL-12 is believed to play a pivotal role in the development of
      psoriasis. Production of IL-12 is modulated by the anti-inflammatory cytokine IL
      10. The effect of PTU on IL-12 and IL-10 levels was, therefore, studied in twelve
      patients with plaque psoriasis. Treatment with 300 mg of PTU daily in divided
      doses for three months produced significant improvement of the PASI and
      histological scores in the patients. Serum IL-12 concentrations were undetectable
      at baseline and did not change with treatment. IL-10 concentrations were 1.39 +/-
      1.49 pg/ml (mean +/- SD) at baseline, and showed no significant change after 2
      weeks (1.63 +/- 1.61 pg/ml and 12 weeks 1.15 +/- 1.58 pg/ml of treatment with
      PTU. The data suggest that the clinical improvement with patients with psoriasis
      treated with PTU is not due to a fall in circulating IL-12 or a rise in IL-10
      concentrations. Although the drug may have effects on lesional production of
      these cytokines this is not reflected in the circulating levels. It is speculated
      that the beneficial effect is likely mediated by an inhibitory effect on
      keratinocyte proliferation or promotion of apoptosis in these proliferated
      keratinocytes.

PMID- 14711145
TI  - Comparing therapy costs for physician treatment of warts.
AB  - To compare the cost of several common modalities used to treat non-genital warts
      in immunocompetent patients, we identified studies published in English using
      standard search strategies and evaluated the literature for the following common
      non-genital wart therapies: cryotherapy with liquid nitrogen, carbon dioxide and
      pulsed-dye laser therapy, topical squaric acid, intralesional bleomycin,
      intralesional interferon alpha injections, and intralesional immunotherapy with
      Candida antigens. Standard treatment algorithms, compiled by dermatologists
      experienced in the treatment of patients with moderate wart burdens, were
      utilized for cost-comparison analyses. Based on the cost analysis model, the
      least expensive treatment option for non-genital warts were carbon dioxide laser
      therapy (157 dollars) and Candida antigen injections (190 dollars). The other
      treatment modalities examined ranged from 495 dollars (bleomycin) to 1227 dollars
      (interferon alpha). Although treatment with the carbon dioxide laser therapy is
      the least expensive, pain and post-procedure complications limit the use of this
      modality.

PMID- 14711146
TI  - Fixed drug eruption to ibuprofen in daughter and father.
AB  - Fixed drug eruption (FDE) is a common cutaneous reaction which may be seen in
      reaction to several medications. The usual etiologic agents associated with FDE
      are phenazones, sulfonamides, and tetracyclines. Often the causative agent is
      made out from the patients history; in some cases, oral challenge or topical
      testing may be required. The pathophysiology of FDE is unclear. Cell-mediated,
      rather than humoral immunity is thought to be involved. Herein we report a case
      of FDE in a daughter and father.

PMID- 14711147
TI  - Doxycycline-induced photo-onycholysis.
AB  - An uncommon manifestation of phototoxicity, photo-onycholysis results in the
      separation of the distal nail from the nail bed. Photo-onycholysis may follow the
      use of various medications or may occasionally be idiopathic. We present a case
      of photo-onycholysis in a patient treated with doxycycline for acne vulgaris.

PMID- 14711148
TI  - Generalized granuloma annulare in a patient with adult onset diabetes mellitus.
AB  - Granuloma annulare is a benign idiopathic disorder, which affects the dermis.
      Several reports have demonstrated an association between granuloma annulare and
      diabetes mellitus. We report the case of a 69-year-old man with an unusual
      presentation of generalized granuloma annulare following the diagnosis of adult
      onset diabetes mellitus.

PMID- 14711149
TI  - Imiquimod for the treatment of Bowen's disease and invasive squamous cell
      carcinoma.
AB  - Topical imiquimod is an immune response modifier FDA approved for the treatment
      of anogenital warts. Recent studies have reported its effectiveness in the
      treatment of some types of basal cell carcinomas. There have also been some case
      reports and case series reporting success treating of squamous cell carcinoma in
      situ with imiquimod. We report two patients with squamous cell carcinoma in situ
      and one with invasive squamous cell carcinoma treated with 5% imiquimod cream.
      Lesions were located on shin, posterior shoulder, and nasal tip. 5% imiquimod
      cream was applied at night for six weeks. Side effects included erythema and
      crusting in one patient. Biopsies taken four weeks after treatment revealed no
      residual squamous cell carcinoma in situ or squamous cell carcinoma. Topical 5%
      imiquimod cream is becoming established as a promising treatment for squamous
      cell carcinoma in situ. It also seems to be an alternative treatment for some
      cases of squamous cell carcinoma.

PMID- 14711150
TI  - Reticulate and stellate acral pigmentation associated with systemic lupus
      erythematosus and high titers of circulating anticardiolipin antibodies: a
      possible association with acral microlivedo.
AB  - A Hispanic man with a twenty-eight year history of systemic lupus erythematosus
      (SLE) and a high titer of anticardiolipin IgG antibodies was noted to have
      reticulate and stellate acral pigmentation. The patient reported that hand
      swelling and erythema developed soon after the diagnosis of SLE was established.
      This episode resolved quickly without recurrence or immediate sequelae. We
      postulate that this eruption was related to SLE and anticardiolipin antibodies.
      Reticulate and stellate acral pigmentation should be considered a possible
      manifestation of SLE and high titers of anticardiolipin antibodies, or a
      consequence of therapy.

PMID- 14711151
TI  - Improvement of acanthosis nigricans on isotretinoin and metformin.
AB  - Acanthosis nigricans (AN) is an eruption of hyperpigmented, velvety thickened
      patches, often with papillomatosis, that occurs symmetrically on any body site
      but most commonly at the axillae, neck, groin, and flexural surfaces. We report a
      case of a 55-year-old obese male who developed acanthosis nigricans with striking
      papillomatosis and tripe palms who experienced improvement on a long-term
      tapering dosage of isotretinoin, with additional benefit with the addition of
      metformin. While oral retinoids have been reported to positively impact AN,
      improvement of AN with metformin has been reported in only two prior cases.
      Combined therapy with isotretinoin and metformin for AN has not been reported
      previously.

PMID- 14711152
TI  - Botox reverses the signs of photoaging.

PMID- 14711153
TI  - From immature to mature pattern ERG and VEP.
AB  - Electrophysiological parameters in children reflect not only pathological
      processes, but also maturation of the visual system. This review investigates
      PERG and PVEP changes in infants and schoolchildren in order to establish the
      time scale for electrophysiological maturation of the visual system. Studies
      using pattern-reversal and pattern-onset stimulation are presented. Maturational
      changes have been found to be rapid in infants and gradual in schoolchildren.
      PERG age-related changes in infants were seen as a decrease in latency and in
      schoolchildren as a decrease in amplitude. PVEP age-related changes in infants
      were seen as a decrease in latency, an increase in amplitude and the development
      of the waveform. In schoolchildren, PVEP changes were more gradual, with a
      decrease in latency, a decrease in amplitude and transformation of the waveform.
      In conclusion, electrophysiological maturation proceeds until adulthood.
      Therefore, in paediatric clinical work, normative values in infants and
      schoolchildren are an important factor in differentiating maturation of the
      visual system from pathological processes.

PMID- 14711154
TI  - Magnocellular and parvocellular developmental course in infants during the first
      year of life.
AB  - The visual system undergoes major modifications during the first year of life. We
      wanted to examine whether the magnocellular (M) and parvocellular (P) pathways
      mature at the same rate or if they follow a different developmental course. A
      previous study carried out in our laboratory had shown that the N1 and P1
      components of pattern visual evoked potentials (PVEPs) were preferentially
      related to the activity of P and M pathways, respectively. In the present study,
      PVEPs were recorded at Oz in 33 infants aged between 0 and 52 weeks, in response
      to two spatial frequencies (0.5 and 2.5 c deg(-1)) presented at four contrast
      levels (4, 12, 28 and 95%). Results indicate that the P1 component appeared
      before the N1 component in the periods tested and was unambiguously present at
      birth. The P1 component showed a rapid gain in amplitude in the following months,
      to reach a ceiling around 4-6 months. Conversely, the N1 component always
      appeared later and then gained in amplitude until the end of the first year
      without reaching a plateau. Latencies were also computed but no developmental
      dissociation was revealed. Results obtained on amplitude are interpreted as
      demonstrating a developmental dissociation between the underlying M and P
      pathways, suggesting that the former is functional earlier and matures faster
      than the latter during the first year of life.

PMID- 14711155
TI  - Development of ERG responses: the ISCEV rod, maximal and cone responses in normal
      subjects.
AB  - PURPOSE: Summarize ISCEV ERG responses from normal infants and children. METHODS:
      The amplitudes and implicit times of the ISCEV rod, maximal dark-adapted and cone
      responses from a total of 409 normal infants (n = 128), children and adult
      controls were compiled. The subjects, aged 1 week to 52 years, were divided into
      seven age groups, including four in infancy (< 52 weeks). The response parameters
      for each age group were summarized as percentiles. RESULTS: In each ISCEV
      condition, the youngest infants (1-5 weeks) had significantly smaller amplitudes
      and longer implicit times than adults. Amplitude increased and implicit time
      decreased systematically with age. CONCLUSIONS: The developmental changes in ERG
      responses are significant. The medians and ranges herein provide provisional
      norms against which the ERG responses from pediatric patients can be compared.

PMID- 14711156
TI  - Standard full-field electroretinography in healthy preterm infants.
AB  - The purpose of this study was to determine electroretinographic parameters
      according to the standard protocol from the International Society for Clinical
      Electrophysiology of Vision (ISCEV) in healthy preterm infants with normal
      fundus. Seventeen healthy preterm infants with normal fundus were recruited and
      divided in two age groups: 3-week group, nine infants with mean adjusted age at
      test = 2.67 +/- 0.92 weeks and 8-week group, eight infants with mean adjusted age
      at test = 7.92 +/- 1.72 weeks. Full-field ERGs were obtained with a Burian-Allen
      bipolar contact lens electrode from the anesthetized cornea in one eye, through a
      fully dilated pupil after 30 min of dark adaptation. The standard ISCEV protocol
      was used and the following responses were recorded: rod, maximal, oscillatory
      potentials, cone and 30 Hz flicker. Median values and 1st, 5th, 95th and 99th
      percentiles for amplitude and implicit time are described for both age groups.
      There was statistically larger amplitude for 30 Hz flicker (t = 2.191; p = 0.046)
      and for cone response (t = 2.307; p = 0.044) in the 8-week-old group.
      Statistically shorter implicit times were found in 8-week group for rod response
      (t = 3.219; p = 0.015), cone response (t = 2.839; p = 0.016) and flicker response
      (t = 3.326; p = 0.005). Shortening of implicit time was evident in the older
      group of preterms and this finding is consistent with other maturational studies
      confirming the anatomical and functional development of the photoreceptors.
      Medians and ranges between the 1st and 99th and the 5th and 95th percentiles can
      be used as a baseline for future comparisons with infants with ROP.

PMID- 14711157
TI  - Faster and more sensitive VEP recording in children.
AB  - PURPOSE: In the difficult-to-test paediatric population, shorter test procedures
      are desirable. This study investigates whether Laplacian analysis of a three
      occipital-electrode montage detects steady-state VEPs (ssVEPs) more often or
      faster in children than a conventional montage, and if so, in which age groups.
      METHODS: Steady-state VEPs (7.78 reversals/s; checkerboard stimulus) to various
      checksizes (60-3', 0.07-14 cpd equivalent) were recorded from 80 normal children
      aged from 1 month to 13 years and 19 adults. Active occipital electrodes were
      placed at Oz and symmetrically either side at 15% of the subject's half-head
      circumference (right occipital and left occipital, RO and LO). The Laplacian
      analysis used 2Oz-(RO+LO) instead of the conventional Oz-Fz. Fourier analysis and
      a circular T2 statistic was used to determine VEP detection time (DT). The number
      of responses detected overall by each analysis method and the effects of age and
      checksize on DT differences between analysis methods were investigated. RESULTS:
      The Laplacian analysis detected more VEPs than the conventional Oz-Fz (95 versus
      84%, p = 0.001) in children's age groups. The Laplacian analysis also provided
      faster response detection to 3' checks in all subjects over the age of five, and
      to 6' and 9' in 7-9-year-olds. CONCLUSION: A Laplacian analysis offers increased
      sensitivity and faster VEP detection over conventional (Oz-Fz) recording in
      children over five for threshold-sized VEPs. Simultaneous use of both
      conventional (Oz-Fz) VEP recording and a Laplacian analysis in all patient ages
      is likely to give faster, more accurate VEP assessments.

PMID- 14711158
TI  - Optic neuritis in children--clinical and electrophysiological follow-up.
AB  - Optic neuritis (ON) in children usually presents with visual loss, relative
      afferent pupillary defect (RAPD), abnormal optic disc appearance, defects of
      visual field and colour vision, as well as with abnormalities of visual evoked
      potentials (VEP). Both, clinical and VEP parameters, improve after the attack;
      the time until recovery, however, is as yet unknown. The aim of this study was to
      follow-up children with ON for 1 year and to determine clinical and VEP recovery.
      Twelve children (six with bilateral, six with unilateral ON) were studied in the
      acute phase and systematically followed-up for 1 year. The results show that
      initially, visual acuity was diminished in all eyes, while after 1 year, in only
      14% of them. Optic disc appearance was abnormal in 83.3% of the eyes in the acute
      phase, and in 85% after 1 year. At the disease onset RAPD could be detected in
      67%, visual field defects in 58.5%, and colour vision defects in 50% of eyes, but
      none of these abnormalities persisted in any eye until the end of study. VEP were
      abnormal in 83% of eyes in the acute phase and in 56% at the final follow-up (at
      6 or 12 months). VEP normalization, when occurred, was mostly observed during the
      first 6 months. Complete clinical and VEP recovery was observed in three
      children. Both, clinical and electrophysiological recovery in children with ON
      were relatively substantial and fast within the first year. VEP improvement may
      indicate better prognosis.

PMID- 14711159
TI  - Alteration of electroretinographic recordings when performed under sedation or
      halogenate anesthesia in a pediatric population.
AB  - Fran The effects of sedation and of halogenate anesthesia on electroretinographic
      recordings were investigated by reviewing the hospital charts of 27 patients who
      were eventually diagnosed free of retinal disease. The same ERG protocol was
      performed in conscious (n=9), sedated (chloral hydrate or pentobarbital sodium,
      n=9) and anesthetized (halothane or isoflurane, in combination with N2O, n=9)
      young patients. Sedation decreased the a- and b-wave amplitude of the scotopic
      bright-flash response, without affecting implicit times. ERG recordings performed
      in photopic conditions showed minimal disturbances. Anesthesia spared the a-wave
      of the scotopic bright-flash response but decreased more severely the b-wave. In
      addition, anesthesia reduced the amplitude and prolonged the implicit time of the
      photopic responses, affecting predominantly the ionotropic glutamate dependent
      OFF components (peak of b-wave, 0P4 and 0P5). The normal retinal physiology is
      affected by sedation and anesthesia through different mechanisms that still
      remain to be fully elucidated. These alterations in electroretinographic
      recordings must be considered when evaluating ERGs obtained under similar
      sedation/anesthetized conditions.

PMID- 14711160
TI  - Examining visual field defects in the paediatric population exposed to
      vigabatrin.
AB  - The antiepileptic drug, vigabatrin, has been linked to a specific pattern of
      visual field loss. The majority of studies have not included the paediatric
      population due to difficulties assessing visual field function. This is a
      particular problem as vigabatrin is effective against infantile spasms. A field
      specific visual evoked potential was developed which consisted of a central
      stimulus (0-5 degrees radius) and a peripheral stimulus (30-60 degrees radius).
      Both stimuli consist of black and white checks which increase in size with
      eccentricity. Responses are recorded from occipital electrodes O2 and O1 referred
      to frontal electrode Fz. Electroretinograms and perimetry was performed were
      possible as a comparison. Thirty-nine children with epilepsy treated with
      vigabatrin aged from 3 to 15 years were included in the study; 35/39 children
      complied with the field-specific VEP, 26/39 complied with the ERG and 11/39
      performed perimetry. Of these results, 18 children had normal ERG responses and
      eight had abnormal response. Visual field testing revealed four children had
      abnormal and seven had abnormal visual field results. The Field-specific VEP
      identified three of four abnormal perimetry results and six of seven normal
      perimetry results, giving a sensitivity of 75% and a specificity of 85.7%. When
      comparing perimetry results with the ERG parameters only the 30-Hz flicker
      amplitude, with a cut-off amplitude below 70 microV, gave a useful sensitivity of
      75% and a specificity of 71%. The field-specific VEP is a useful alternative
      method that is both well tolerated by young children and gives a reliable
      indication of likely peripheral visual field loss associated with vigabatrin. The
      defect appears to have a similar prevalence in children as it does in adults.

PMID- 14711161
TI  - Longitudinal changes in photopic OPs occurring with vigabatrin treatment.
AB  - PURPOSE: Vigabatrin (gamma-vinyl-GABA) is an antiepileptic drug successful in the
      management of infantile spasms. Photopic ERGs were tested in children followed
      longitudinally before and during vigabatrin treatment. METHODS: Subjects were 26
      infants (age range 1.5-24 months, median 7.6 months) on vigabatrin treatment who
      had been tested on multiple visits (two to four visits; mean, three visits).
      Eighteen of these were assessed initially before starting vigabatrin therapy and
      eight were assessed within 1 week of initiation of the drug. ERGs were recorded
      at 6-month intervals. Standard ISCEV protocol with Burian-Allen bipolar contact
      lens electrodes (standard flash 2.0 cd.s/m2) was used. Although ISCEV standards
      were followed, a higher flash intensity (set at 3.6 cd.s/m2) was chosen for
      single-flash cone assessment to provide a better definition of OPs. Photopic OPs
      were divided into categories of early OPs and late OP (OP4). Responses were
      compared with age corrected limits extrapolated from our lab control database.
      RESULTS: Results showed differential effects of vigabatrin on the summed early OP
      amplitudes versus the late OP (OP4) and cone b-wave amplitude. The early OPs
      showed significant decrease (p = 0.0005, repeated measures analysis of variance)
      after 6 months and remained decreased for the duration of treatment. There was no
      significant change seen in the late OP. The cone b-wave amplitude showed initial
      increase (p = 0.04) after 6 months, followed by a decrease after 18 months; a
      trend similar to that of the late OP. CONCLUSION: Early photopic OPs were
      disrupted more than the late OP, suggesting relative deficit in the ON
      (depolarizing) retinal pathways.

PMID- 14711163
TI  - A research-based tool for identifying and strengthening culturally competent and
      evaluation-ready HIV/AIDS prevention programs.
AB  - Recent literature on racial disparities in HIV/AIDS and effective HIV/AIDS health
      service delivery efforts has underscored the importance of cultural sensitivity,
      relevance and competence in reducing such disparities and providing effective
      health service delivery. Less work has been done on the role of cultural
      competence in the delivery of effective HIV/AIDS prevention programs, perhaps
      because few such prevention programs aimed at minority populations have to date
      been demonstrated as effective. This article surveys the various ways that the
      concept of cultural competence has been studied, extends the concept to the field
      of HIV/AIDS prevention, and presents a simple-to-use instrument that
      operationalizes the concept for use with HIV/AIDS prevention programs. The
      article also explores the idea of evaluation readiness among HIV/AIDS prevention
      programs in the hope of eventually enlarging the pool of minority-focused
      HIV/AIDS programs demonstrated as effective. The resultant tool can serve as a
      research-based framework that: (a) serves as a cost-effective way to select
      promising programs--especially promising minority-focused programs-for rigorous
      outcome evaluation; (b) advances the field of HIV/AIDS prevention research by
      providing a conceptual framework for studying the relationship between cultural
      competence and program effectiveness; and (c) serves as a framework for building
      capacity in HIV/AIDS prevention programs, pointing to ways in which such programs
      can be strengthened.

PMID- 14711162
TI  - Changes in the electroretinogram resulting from discontinuation of vigabatrin in
      children.
AB  - Electroretinograms (ERGs) have been recorded longitudinally in children before
      and during treatment with the antiepileptic drug vigabatrin for the past 3.5
      years. Vigabatrin induced changes in ERG responses occur in children; the most
      dramatic changes occur in the oscillatory potentials. The purpose of this study
      was to identify changes in ERG responses associated with discontinuation of
      vigabatrin treatment. If vigabatrin-induced changes reverse after discontinuation
      of the drug we infer that the original change is not an indicator of toxicity.
      ERG data were analyzed from 17 children who discontinued vigabatrin therapy. The
      duration of treatment ranged from 5 to 52 months, the age for the first ERG
      ranged from 6 to 38 months (median 10 months). ERGs were tested using the
      standard protocol established by the International Society for Clinical
      Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes.
      In addition to standard responses we recorded photopic oscillatory potentials
      (OPs). During vigabatrin treatment OPs show a greater change than other ERG
      responses, with the early occurring wavelets from the photopic OPs showing the
      greatest change. With discontinuation of vigabatrin the amplitude of the early
      wavelets of the photopic OPs increased dramatically compared with amplitudes
      while taking the drug (paired t-test, p = 0.000075). The scotopic oscillatory
      potentials also show some recovery. Although changes in oscillatory potentials
      may occur with vigabatrin toxicity, a large change likely occurs with a non-toxic
      pharmacological effect of vigabatrin on GABAergic amacrine cells in the inner
      plexiform layer. Reduction of OPs in children on vigabatrin may not be related to
      toxicity.

PMID- 14711164
TI  - Respondent perspectives on self-report measures of condom use.
AB  - There is much concern about the validity of self-reported condom use. In an
      effort to improve self-report measures, a study using semistructured interviews
      was conducted to elicit the perspectives of women who had participated in a
      microbicide clinical trial in which self-reports of condom use were included.
      Women were asked about their comprehension of the questions, how they remembered
      their condom use and their sensitivity to the expectations of the interviewer,
      and how this affected their answers. Although most women believed they were
      accurate in their answers about condom use, a number of women admitted to
      exaggerating their condom use or believed other women did, citing concerns
      related to interviewers' expectations of them as the primary reason. Most women
      did not believe that comprehension or memory was a problem and a number were able
      to articulate strategies for remembering their condom use.

PMID- 14711165
TI  - Prevalence and risk behaviors of Chinese men who seek same-sex partners via the
      internet in Hong Kong.
AB  - To examine the prevalence of Internet sex networking among men who have sex with
      men (MSM) in Hong Kong and risk behaviors associated with the behavior, a
      telephone survey of 15,230 Hong Kong Chinese men aged 18-60 was conducted. Of the
      283 active MSM (having engaged in some MSM behaviors in the last 6 months)
      identified, 17.7% had networked for MSM partners via the Internet in the last 6
      months. Younger age (odds ratio [OR] for age < or = 25 vs. age >25 = 4.67, 95%
      confidence interval [CI] = 2.35-9.28) and being an anal-sex MSM (OR = 4.72, 95%
      CI=2.36-9.44) were independent predictors of Internet sex networking. Being an
      Internet sex networker was associated with some risk behaviors such as having
      contracted a sexually transmitted disease (adjusted OR = 4.79, 95% CI = 1.34
      17.11), having had > or = 3 MSM partners (adjusted OR = 4.74, 95% CI = 2.20
      10.23), and having engaged in anal sex (adjusted OR = 3.95, 95% CI = 1.89-8.23).
      HIV prevention programs for MSM should thereby include Internet-based
      interventions.

PMID- 14711166
TI  - HIV/AIDS knowledge, beliefs, and behavior among women of childbearing age in
      India.
AB  - This study investigated the relationships of health beliefs and HIV/AIDS
      knowledge with frequency of condom use among women of childbearing age in four
      major Indian cities. Surveys were completed by 210 women attending six primary
      health care centers. Among the sexually active women (N = 139), 68% noted rare or
      no use of condoms during intercourse. Perceived benefits (p < .05) and normative
      efficacy in requesting condom use (p = .01) were related to a greater frequency
      of condom use. About 54% of women knew that breast milk could transmit HIV, but
      fewer than a third were aware that an HIV-positive mother does not always infect
      her infant at delivery. Most participants endorsed HIV testing for women prior to
      pregnancy. Approximately three fourths of participants advocated abortion for HIV
      seropositive pregnant women. Intervention efforts may benefit from dispelling
      misconceptions about AIDS (particularly regarding vertical transmission),
      emphasizing perceived benefits and women's efficacy in requesting condom use,
      increasing the availability of HIV testing, and highlighting choices for
      seropositive women of reproductive age as alternatives to abortion.

PMID- 14711167
TI  - HIV and STD testing in prisons: perspectives of in-prison service providers.
AB  - Because individuals at risk for HIV and STDs are concentrated in prisons and
      jails, incarceration is an opportunity to provide HIV and STD testing. We
      interviewed 72 service providers working in U.S. prisons in four states about
      their experiences with and perceptions regarding HIV and STD testing in prison.
      Providers' job duties represented administration, education, security,
      counseling, and medical care. Providers' knowledge of prison procedures and
      programs related to HIV and STD testing was narrowly limited to their specific
      job duties, resulting in many missed opportunities for prevention counseling and
      referral. Suggestions include increasing health care and counseling staff so
      posttest counseling can be provided for those with negative as well as positive
      test results, providing additional prevention programs for incarcerated persons,
      improving staff training about HIV and STD testing, and improving communication
      among in-prison providers as well as between corrections and public health staff.

PMID- 14711168
TI  - HIV risk behavior history of prison inmates in Hungary.
AB  - As part of an intervention in correctional facilities in Hungary, we conducted
      research on AIDS-related attitudes and the HIV risk behavior history of 551 male
      and 81 female inmates to assess needs for and to tailor AIDS education programs.
      Although lifetime injection drug use was uncommon (8% of men, 3% of women), many
      Hungarian inmates had engaged in unprotected sex and had had high-risk sex
      partners: a quarter of men had primary partners who sold sex, about half of them
      had sex with female prostitutes, 13% of women had worked as prostitutes, and 9%
      of all inmates indicated having had sex in prison. Because many prison inmates
      may constitute a potential bridge population for the sexual transmission of HIV
      between the general population and high-risk populations, interventions among
      prison inmates may provide an opportunity to reach an at-risk population and to
      prevent the wider spread of sexually transmitted HIV.

PMID- 14711169
TI  - Assessing the HIV/AIDS health services needs of African immigrants to Houston.
AB  - This study investigated HIV/AIDS knowledge, risk behaviors and perceptions, and
      access to services among Black immigrants from more than 20 African nations to
      Houston, Texas, United States. Three hundred nine respondents completed a 98-item
      self-administered questionnaire on HIV/AIDS knowledge, risk behaviors, access to
      services, and stigma. Data analysis revealed this population to be highly
      educated (70.9% had educational attainment levels beyond high school), with a
      plurality motivated to immigrate to the United States for academic reasons
      (45.0%). As a group they displayed a high level of knowledge about modes of HIV
      transmission. Generally, Christian background respondents had higher knowledge
      than those of Muslim background. Nevertheless, 36.3% reported that they had never
      used a condom, with the overwhelming majority of respondents reporting low self
      perceived risk for contracting HIV (79.5%). These findings, together with the
      persistent practice of traditional rituals such as body scarring/tattooing by a
      significant minority (20.1%), a lack of awareness about vertical transmission
      (16.3% of women; 29.9% of men), and discouraging scores on an HIV stigma
      perception scale, suggest that a targeted campaign to raise awareness in this
      population is warranted.

PMID- 14711170
TI  - Determination of cholesterol absorption in humans: from radiolabel to stable
      isotope studies.
AB  - Hypercholesterolemia is a major health risk. Dietary cholesterol absorption is
      one important factor affecting levels of plasma and tissue cholesterol.
      Considerable effort has thus been devoted to develop reliable in vivo clinical
      methodologies to determine dietary cholesterol absorption in humans. The present
      paper summarises radiolabelled experiments and major advances in stable isotope
      technologies to determine cholesterol absorption. Initially, direct methods
      employing gastro-intestinal intubation were developed. Later, indirect methods
      using oral-faecal cholesterol balance permitted calculation of cholesterol mass
      absorption. Once the use of radiolabelled [3H, 14C]cholesterol balance was
      developed in healthy humans, it was finally possible to distinguish exogenous and
      endogenous cholesterol. Non-invasive and safer stable isotope (2H, 13C, 18O)
      labelled cholesterol tracers then replaced radioisotopes for use in infants and
      adults. Stable isotopes and radioisotopes showed identical cholesterol kinetics.
      The most promising contemporary stable isotope assessment of cholesterol
      absorption is a dual stable isotope dual tracer approach based on simultaneous
      administration of oral and intravenous differentially labelled cholesterol
      tracers, followed by plasma sampling for 3-4 d. Online GC/Combustion/IRMS and
      GC/Pyrolysis/IRMS allow minimal amounts of dual stable isotope cholesterol
      tracers to be detected. Using the dual stable isotope dual tracer approach, the
      percent cholesterol absorption in adult volunteers has been determined to be 50
      70%.

PMID- 14711171
TI  - Box-modeling of bone and tooth phosphate oxygen isotope compositions as a
      function of environmental and physiological parameters.
AB  - A time-dependent box model is developed to calculate oxygen isotope compositions
      of bone phosphate as a function of environmental and physiological parameters.
      Input and output oxygen fluxes related to body water and bone reservoirs are
      scaled to the body mass. The oxygen fluxes are evaluated by stoichiometric
      scaling to the calcium accretion and resorption rates, assuming a pure
      hydroxylapatite composition for the bone and tooth mineral. The model shows how
      the diet composition, body mass, ambient relative humidity and temperature may
      control the oxygen isotope composition of bone phosphate. The model also computes
      how bones and teeth record short-term variations in relative humidity, air
      temperature and delta18O of drinking water, depending on body mass. The
      documented diversity of oxygen isotope fractionation equations for vertebrates is
      accounted for by our model when for each specimen the physiological and diet
      parameters are adjusted in the living range of environmental conditions.

PMID- 14711172
TI  - Magnesium enrichment and distribution in plants.
AB  - Food products enriched with stable isotopes are used in nutrition to study the
      metabolic fate of nutrients in humans. This study reports on the labeling of
      green beans, white beans, soybeans and wheat with a stable isotope of magnesium
      (25Mg) obtained in greenhouse conditions for further studies on magnesium
      bioavailability. Soybean and green bean are the most efficient plant species to
      obtain large amounts of edible parts rapidly with a minimum loss of labeled Mg in
      other parts of the plants. The results obtained showed that a relatively high
      percentage of the magnesium found in seeds (grains/beans) can come from the
      redistribution of magnesium previously accumulated in other organs.

PMID- 14711173
TI  - Isotope composition of Zelkova serrata leaves as an indicator of atmospheric
      pollution in Japan.
AB  - In spite of increasing concern regarding the effects of greenhouse gases,
      atmospheric CO2 concentration continues to increase, with current levels now as
      high as 370 ppm. This elevated CO2 concentration influences not only atmospheric
      characteristics, but also ground vegetation: leaf structure, chemical composition
      and carbon-isotope composition are all affected. It was with this in mind that we
      investigated the viability of coupling an isotopic and a botanical approach to
      determine leaf interaction in relation to atmospheric pollution levels. Results
      show that, among the botanical indexes considered, the most reliable proxy of
      atmospheric CO2 levels would appear to be leaf mass per area (LMA), which
      increases with pollution. Our study also shows that LMA determination coupled
      with carbon-isotope compositions is a sensitive tracer of the local pollution
      level variations.

PMID- 14711174
TI  - Isotopic study of post-anthesis foliar incorporation of sulphur and nitrogen in
      wheat.
AB  - Nitrogen (N) and sulphur (S) supplies have a strong influence on the quality and
      quantity of wheat storage proteins, which play an important role in the bread
      making process. In order to relate the incorporation and distribution of foliar N
      and S fertilisers at the post-anthesis stage to the quality of wheat, 15N and 34S
      isotopes were used as tracers. The incorporation of these tracers in different
      plant parts (leaves, stems, ears) and in each storage protein fraction (gliadins,
      HMW and LMW glutenin subunits) was determined by isotopic ratio mass spectrometry
      coupled with an elemental analyser (EA-IRMS). By this means, the true recovery
      coefficient of N and S (TRCNfertiliser and TRCSfertiliser) and the N and S
      derived from fertilisers (Ndff and Sdff) could be determined. The TRCNfertiliser
      and TRCSfertiliser values of the different plant parts provide evidence of the
      applied N and S assimilation and translocation from wheat leaves to the seeds.
      The determination of Ndff and Sdff incorporated into storage proteins shows the
      efficiency and the influence of N and S incorporation into each storage protein
      fraction. Moreover, a favourable stage for fertiliser application can be
      determined by the TRCNfertiliser values in the grain and in the whole plant. The
      fertilisers enriched in stable isotope used in the culture techniques can be a
      means of understanding the effectiveness of fertilisers in the expression of
      wheat quality.

PMID- 14711175
TI  - The use of stable isotopes to evaluate water mixing and water use by flood plain
      trees along the Garonne valley.
AB  - Before the confluence of the Tarn, the Garonne valley was the driest area in the
      entire south-west of France, due to the relatively low rainfall and low summer
      discharge of the Garonne River and its tributaries. The natural abundance of the
      stable isotope of oxygen (18O) and ionic charge of surface and ground water were
      used to estimate the water source for the Garonne River and phreatic subsurface
      water. We also measured these constituents in the sap of trees at several flood
      plain sites to better understand the source of water used by these trees. 18O
      signatures and conductivity in the Garonne River indicated that the predominance
      of water was from high altitude surface runoff from the Pyrenees Mountains.
      Tributary inputs had little effect on isotopic identity, but had a small effect
      on the conductivity. The isotopic signature and ionic conductivity of river water
      (delta18O: -9.1 per thousand to -9.0 per thousand, conductivity: 217-410
      microS/cm) was distinctly different from groundwater (delta18O: -7.1 per thousand
      to -6.6 per thousand, conductivity: 600-900 microS/cm). Isotopic signatures from
      the sap of trees on the flood plain showed that the water source was shallow
      subsurface water (<30 cm), whereas trees further from the river relied on deeper
      ground water (>1 m). Trees at both locations maintained sap with ionic charges
      much greater (2.3-3.7x) than that of source water. The combined use of 18O
      signatures and ionic conductivity appears to be a potent tool to determine water
      sources on geographic scales, and source and use patterns by trees at the local
      forest scale. These analyses also show promise for better understanding of the
      effects of anthropogenic land-use and water-use changes on flood plain forest
      dynamics.

PMID- 14711176
TI  - Determining the content and 13C abundance of total dissolved carbon in water
      samples by TOC analyser-mass spectrometer coupling.
AB  - A combined system consisting of a TOC analyser connected to a quadrupole MS was
      recently described as a way of measuring the N content and the 15N abundance of
      total dissolved nitrogen in aqueous samples. This work examines whether this
      combination of instruments can also be used for the 13C determination of the
      total dissolved carbon in aqueous samples. A level of precision good for 13C
      enriched samples was achieved with a relative standard deviation of <3%. By using
      an isotope ratio MS instead of the quadrupole MS employed here, TOC-MS coupling
      also ought to be suitable for determining natural 13C abundances.

PMID- 14711177
TI  - Noninvasive detection of coronary artery bypass graft patency by intravenous
      electron beam computed tomographic angiography.
AB  - This study evaluates the usefullness of intravenous electron beam computed
      tomographic angiography (EBA) for the detection of coronary artery bypass graft
      patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary
      artery bypass graft surgery. EBA was performed a few days before selective bypass
      graft angiography (SGA). Forty axial cross-sections of angiographic images of the
      heart were acquired consecutively by an electrocardiographic trigger signal at
      40% of the RR interval, which corresponds to the end-systolic phase. EBA data
      were reconstructed as a three-dimensional shaded surface display of the heart and
      bypass grafts. Detectability of the patency of bypass gratis was evaluated,
      taking selective angiographic images of the bypass grafts as a gold standard. One
      hundred and nine grafts (96%) out of 114 grafts were subjected to evaluation: 37
      grafts were left internal mammary artery grafts (LIMA), 7 were right internal
      mammary artery grafts (RIMA), 6 were gastroepiploic artery grafts (GEA), 7 were
      free gastroepiploic artery grafts with venous drainage (free-GEA), 7 were radial
      artery grafts (RAG), and 45 were saphenous vein gratis (SVG). The sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of EBA were 98%, 100%, 100%, 91%, and 98%, respectively. EBA sampled at the end
      systolic period was determined to be useful for the detection of coronary artery
      bypass graft patency and occlusion.

PMID- 14711178
TI  - Time course of erythrocyte antioxidant activity in patients treated by
      thrombolysis for acute myocardial infarction.
AB  - The deleterious effects of free radicals in acute myocardial
      ischaemia/reperfusion are rather well known. However, the possibility that
      thrombolysis positively affects the recovery of blood antioxidant capacity in the
      later postinfarction period, and thus contributes to the better overall outcome
      of these patients, has not yet been investigated. We followed the time course of
      erythrocyte antioxidant activity in 45 patients with first acute myocardial
      infarction (AMI), who were treated with streptokinase. Success of thrombolysis
      was evaluated by noninvasive clinical signs of reperfusion using continuous
      vector cardiography. The patients were divided into two groups according to
      successful or unsuccessful, reperfusion, The control group consisted of 24
      healthy subjects. Glutathione peroxidase (GPX) and superoxide dismutase (SOD)
      were determined immediately after admittance to the hospital (0 hours) and after
      subsequent thrombolytic therapy (1.5, 6, 12, and 24 hours after initiation of
      infusion of streptokinase), and 2, 4, and 8 days after AMI. Patients with AMI had
      decreased antioxidant enzyme activity at the time of admit- tance to the
      hospital, showing that the oxidative/antioxidative balance is disturbed early
      during the ischemic phase of AMI. In AMI patients without successful reperfusion,
      erythrocyte antioxidant enzyme activity remains low during the postinfarction
      period of 7 days. It can be concluded that prolonged ischemia reduces antioxidant
      enzyme activity. AMI patients with successful reperfusion have a significant rise
      in the activity of antioxidant enzymes within the first hours after thrombolysis,
      followed by a decrease until the third postinfarction day. During the subsequent
      postinfarction period, erythrocyte antioxidant activity gradually recovered and
      reached control levels. These beneficial effects of reperfusion on erythrocyte
      antioxidant status might contribute to the better overall prognosis of these
      patients.

PMID- 14711179
TI  - Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells
      after myocardial infarction.
AB  - Tumor necrosis factor (TNF) family proteins including TNF-alpha and Fas (CD95)
      ligand have been implicated in the development of acute myocardial infarction
      (AMI). We studied whether AMI patients displayed up-regulation of another TNF
      family member, TNF-related-apoptosis-inducing ligand (TRAIL), on peripheral blood
      mononuclear cells (PBMCs). We compared expression of TRAIL on PBMCs from 26
      patients in the acute phase of AMI with that on PBMCs from 16 healthy control
      subjects using flow cytometry and RT-PCR. In addition, expression of TRAIL
      protein on PBMCs from patients in the acute phase of AMI was also compared with
      that from the same patients 7 days later. Furthermore, we compared the expression
      of TRAIL protein on CD4+, CD8+, CD14+, and CD19+ cells from patients in the acute
      phase of AMI with that from control subjects using flow cytometry. Finally,
      expression of the TRAIL receptors (TRAILR)-1 and TRAILR-2 in human cardiomyocytes
      was examined immunohistochemically. Expression of TRAIL protein was significantly
      higher in the acute phase of AMI than in control subjects. Expression of TRAIL
      protein was significantly higher in the acute phase of AMI than 7 days later.
      TRAIL mRNA expression in the acute phase of AMI was higher than in control
      subjects. Expression of TRAIL protein on CD4+ and CD14+ cells from AMI patients
      was significantly higher than that from control subjects. Expression of TRAILR-1
      and TRAILR-2 in human cardiomyocytes was confirmed immunohistochemically. TRAIL
      on infiltrating CD4 and CD146 cells may be involved in the induction of
      cardiomyocyte apoptosis after AMI.

PMID- 14711180
TI  - Relation between the timing of the last preinfarction angina and microvascular
      reperfusion in patients with recanalized acute myocardial infarction.
AB  - In patients with recanalized acute myocardial infarction (AMI), the relation
      between the timing of preinfarction angina (PA) and microvascular reperfusion
      remains unclear. A total of 186 patients (114 with anterior and 72 with inferior
      AMI) who had total occlusion and TIMI 3 recanalization < or = 6 hours from the
      onset of AMI were divided into 4 groups according to the time interval between
      the last episode of PA and the onset of AMI: < or = 2 hours (group A, n = 52); 2
      to 48 hours (group B, n = 43), > or = 48 hours (group C, n = 33), and no PA
      (group D, n = 58). The angiographic myocardial blush grade, a marker of
      microvascular reperfusion, was retrospectively assessed immediately after
      recanalization. There were no differences in baseline characteristics, except for
      sex among the 4 groups. Myocardial blush grade 3 was more frequent (42% vs 21%,
      9%, and 14%) and peak creatine kinase was lower (2659 vs 3455, 4422, and 4622
      mU/mL) in group A than in groups B, C, and D (all P < 0.05). Multivariate
      analysis showed that PA occurring < or = 2 hours before AMI (OR 3.88, P < 0.05),
      a smaller summed ST-segment elevation before recanalization (OR 0.84, P < 0.01),
      earlier time to recanalization (OR 0.52, P < 0.05), and interior AMI (OR 4.87, P
      < 0.05) were independently associated with adequate microvascular reperfusion. We
      conclude that PA < or = 2 hours before the onset of AMI is independently
      associated with adequate microvascular reperfusion after recanalization in
      patients with AMI.

PMID- 14711181
TI  - Relationship between collateral blood flow and microvascular perfusion after
      reperfused acute myocardial infarction.
AB  - During acute occlusion of an epicardial vessel collaterals preserve the
      microvascular perfusion and limit the extent of myocardial damage. Pressure
      derived collateral flow index (CFIp) assessed by intracoronary pressure
      measurement allow us to quantify collateral vessel development. The angiographic
      myocardial blush (MB) scores, based on the contrast dye density and washout in
      the infarcted myocardium, provide important information about microvascular
      perfusion after acute myocardial infarction (AMI). In this study we assessed the
      microvascular perfusion with MB and studied the relation between CFIp in patients
      with AMI who treated with thrombolytic therapy and TIMI grade III flow restored
      in the infarct related artery (IRA). Forty-one patients with AMI who were treated
      with thrombolytic therapy and underwent stent implantation (mean of 3 days after
      AMI) to the IRA were included in this study. After angiography, CFIp was
      calculated as the ratio of simultaneously measured coronary wedge pressure-
      central venous pressure (Pv) to mean aortic pressure--Pv. Myocardial blush was
      graded densitometrically based on visual assessment of the relative contrast
      opacification of the myocardial territory subtended by the infarct vessel. There
      was a statistically significant correlation between CFIp and post-stent
      myocardial blush grades (P < 0.01, r = 0.70). There was a significant difference
      in mean CFIp among myocardial blush grades implying that higher CFIp is
      associated with better MB (0.39 +/- 0.11 in grade 3, 0.32 +/- 0.10 in grade 2,
      0.24 +/- 0.09 in grade 1, and 0.16 +/- 0.08 in grade 0, P < 0.01). Well developed
      collaterals can limit microvascular damage by preserving microvascular perfusion.
      A higher pressure-derived collateral flow index is associated with better tissue
      level perfusion as evidenced by the higher myocardial blush score.

PMID- 14711182
TI  - Plasma homocysteine levels in patients with early coronary artery stenosis and
      high risk factors.
AB  - The aim of this study was to study the relationship between plasma homocysteine
      (Hcy), folic acid, vitamin B12 and early coronary artery disease (early-CAD) and
      high coronary risk factors. The plasma Hcy levels of 58 cases with early-CAD and
      31 subjects without CAD were measured using high-performance liquid
      chromatography (HPLC) with fluorescence detection. Plasma folic acid and Vitamin
      B12 levels were measured with radioassay method. The plasma Hcy level was
      significantly higher in the early-CAD patients than in the controls [(13.7 +/-
      5.1) micromol/L vs (10.3 +/- 5.7) micromol/L]. The plasma folic acid and Vitamin
      B12 levels were significantly lower in the early-CAD patients than in the
      controls. The plasma Hcy level was higher in patients with more than 3 risk
      factors of CAD than in patients with 1 or 2 risk factors and in the controls
      [(17.3 +/- 5.1) micromol/ L vs (12.9 +/- 4.8) micromol/L, (7.8 +/- 2.5)
      micromol/L]. Other than gender, all classical coronary risk factors were related
      to the elevated Hcy level. Hcy levels were elevated in patients with early-CAD
      and with high risk factors. Hyperhomocysteinemia plays an important role in the
      pathogenesis of CAD.

PMID- 14711183
TI  - Pravastatin reduces the incidence of cardiac events among patients with
      myocardial infarction.
AB  - We retrospectively compared the incidence of cardiac events in myocardial
      infarction (MI) patients treated in our departments between 1990 and 1999 with
      pravastatin or without cholesterol-lowering agents. Our aim was to evaluate the
      efficacy of pravastatin in the secondary prevention of MI. Cardiac events-
      defined as fatal or nonfatal recurrent MI, sudden cardiac death, and death from
      congestive heart failure--occurred in 8 (2.2%) of 356 MI patients treated with
      pravastatin (17.1 cases/1.000 person x year) and in 39 (5.6%) of 700 MI patients
      not treated with cholesterol-lowering agents (54.3 cases/1000 person x year),
      which represented a significant decline among those taking pravastatin (P < 0.05,
      odds ratio: 0.39, 95% (CI: 0.18-0.84). Likewise, total mortality was
      significantly lower among patients treated with pravastatin (18 cases, 5.1%; 38.4
      cases/1,000 person x year vs 77 cases, 11.0%; 107.2 cases/1,000 person x year, P
      < 0.01, odds ratio: 0.43, 95% CI: 0.25-0.73). Subgroup analysis revealed a
      significantly lower incidence or cardiac events in the pravastatin group for 6 of
      the items among 53 patient characteristics, and was lower but not significant for
      45 items and was greater but not significant only for 2 items. Furthermore,
      multivariate analysis confirmed pravastatin to be a useful factor for preventing
      the occurrence of cardiac events in MI patients (P < 0.05, odds ratio: (0.44, 95%
      CI: 0.20-0.95), and Kaplan-Meier curves also showed pravastatin to significantly
      reduce the incidence of both cardiac events and total mortality. These findings
      are consistent with those previously reported by several large-scale clinical
      trials carried out in Western countries, and demonstrate that pravastatin is
      useful for secondary prevention of MI in Japanese patients.

PMID- 14711184
TI  - Comparison of initial efficacy and long-term follow-up of heparin-coated Jostent
      with conventional NIR stent.
AB  - The implantation of heparin-coated stents was reported to be well tolerated, but
      there are conflicting results about acute in-hospital complications. (sub)acute
      thrombosis rates, and long-term follow-up compared to uncoated stents. We
      compared the angiographic and clinical results after coronary placement of two
      stent models: the heparin-coated premounted Jostent and the uncoated premounted
      NIR stent. Of 710 patients revascularized, a total of 426 patients received
      Jostent (n = 230) or NIR stent (n = 196) implantation. The primary end points
      were acute or subacute thrombosis, urgent CABG, AMI or death, while the secondary
      end points were the comparison of the restenosis rates of the stents at the 6th
      month and of the functional angina classification of the stent groups at the 1st,
      6th and 12th months. There were no significant differences between the Jostent
      and NIR stent groups regarding angiographic and procedural success. Acute
      thrombosis rates in the Jostent and NIR stent groups were similar while no
      subacute thrombosis was observed in either group. The major adverse cardiac event
      rates of the groups also did not differ. Angiographic restenosis occurred in 17%
      of the Jostent group and 16% of the NIR stent group (NS). The combined clinical
      and angiographic restenosis rate was also similar between the Jo and NIR groups
      (19% and 18%, respectively). Comparison of functional angina classes at the 1st,
      6th and 12th months revealed no significant difference between the study groups.
      In conclusion, when compared with implantation of an uncoated premounted NIR
      stent, implantation of a heparin-coated premounted Jostent does not provide any
      more benefit with respect to initial efficacy, sub(acute) thrombosis and 6-month
      restenosis rates and 12-month clinical outcomes.

PMID- 14711185
TI  - Effects of enoxaparin and nadroparin on major cardiac events in high-risk
      unstable angina treated with a glycoprotein IIb/IIIa inhibitor.
AB  - Clinical trials have reported the beneficial effects of platelet glycoprotein
      (GP) IIb/IIIa receptor antagonists and low-molecular-weight heparins (LMWH) on
      major cardiac events (MACE) in patients presenting with unstable angina or non-ST
      elevation myocardial infarction. A number of studies have documented the
      significant superiority of low-molecular-weight heparins, especially enoxaparin,
      over unfractionated heparin in the treatment of acute coronary syndromes. The
      purpose of this study was to compare the effects of two different LMWHs,
      enoxaparin and nadroparin, accompanied by platelet GP IIb/IIIa inhibition on MACE
      in high-risk unstable angina. The study was designed as an open-label and
      observational study. Sixty-eight patients presenting with unstable angina
      associated with high-risk criteria were randomly assigned to treatment with
      enoxaparin plus tirofiban (36 patients, mean age 57 +/- 11) or nadroparin plus
      tirofiban (32 patients, mean age: 58 +/- 8). In-hospital MACE including acute
      myocardial infarction (AMI), recurrent refractory angina, death, stroke, and
      urgent revascularization were compared between the study groups. Patient
      characteristics and durations of LMWH and tirofiban treatments were not different
      between the study groups. Coronary artery risk factors, except family history
      (which was observed more frequently in the enoxaparin group, P = 0.02), were also
      similar. MACE between the enoxaparin and nadroparin groups including AMI (5.5%,
      6%), recurrent refractory angina (19%, 12%), death (0%, 3%), stroke (was not
      observed in either group), urgent revascularization (14%, 12%) and total MACE
      (19%, 15%) were not different. Enoxaparin and nadroparin, accompanied by GP
      IIb/IIIa inhibitor therapy, have similar effects on the development of major
      cardiac events in patients presenting with unstable angina and high-risk
      characteristics.

PMID- 14711186
TI  - Diffuse intimal thickening of coronary arteries in slow coronary flow.
AB  - Intravascular ultrasound imaging can detect intimal thickening and is suitable
      for detection of early atherosclerosis, which cannot be detected by conventional
      angiography. The aim of the present study was to investigate the epicardial
      coronary morphology and intracoronary pressure in relation to slow coronary flow
      (SCF). The study population consisted of 19 patients with SCF [11 (57.9%)
      females; 55.95 +/- 9.42 years]. Proximal, middle, distal and mean total vessel
      area, lumen area, intima + media area (IMA), percent IMA, and maximal intima +
      media (I + M) thickness were calculated and compared to healthy subjects.
      Proximal, middle, distal and mean I + M thickness, IMA, and % IMA of patients
      with SCF were found to be significantly higher than those of control subjects.
      Longitudinally extended massive calcification throughout the epicardial arteries
      was found in 13 (68.49%) patients with SCF and regional calcification was found
      in 6 (31.6%) patients with SCF. Proximal and distal pressure gradients of
      patients with SCF were determined to be 15.84 +/- 12.11 mmHg in the intracoronary
      pressure measurements. Fractional flow reserve values were significantly lower
      than the normal population (0.83 +/- 0.13, P < 0.0001). This study indicates that
      patients with SCF have diffuse intimal thickening, widespread calcification along
      the vessel wall and atheroma which does not cause luminal irregularities in
      coronary angiography, and a pressure gradient between proximal and distal
      segments of epicardial coronary arteries with SCF. Based on these results, we
      believe that SCF may be a form of diffuse atherosclerosis involving both the
      microvascular system and epicardial coronary arteries.

PMID- 14711187
TI  - External cardioversion in patients with persistent atrial fibrillation: a
      reappraisal of the effects of electrode pad position and transthoracic impedance
      on cardioversion success.
AB  - The optimal methods to perform external cardioversion of atrial fibrillation (AF)
      have yet to be conclusively determined. This study was performed to examine the
      relative efficacy of different pad positions on cardioversion success and the
      relationship between the transthoracic impedance (TTI) and energy requirement for
      AF cardioversion. Seventy patients with persistent AF undergoing elective
      cardioversion were randomly assigned to an electrode pad position situated either
      over the ventricular apex-right infraclavicular area (AL group, n = 31 ) or over
      the right lower sternal border-left infrascapular area close to the spine (AP
      group, n = 39). Energy was delivered at an initial 100 joules (J) and then
      increased to 150 J, 200 J, 300 J, and 360 J if needed. Energy and TTI readings
      were recorded. Mean TTI was significantly lower in the AP group than in the AL
      group. However, the cumulative success rates at each energy level were similar in
      the two groups (23% vs 19.4%, 41% vs 45.2%, 66.7% vs 74.2%, 79.5% vs 77.4%, and
      84.6% vs 83.9% at 100 J, 150 J, 200 J, 300 J and 360 J, respectively). In the AP
      group, converters showed slightly lower TTI compared to nonconverters. In the AL
      group, converters showed significantly lower TTI compared to nonconverters.
      However, for all patients as a group, TTI was the only predictor for
      cardioversion success and showed a significant relationship to the energy
      required for cardioversion, which can be described by a quadratic equation.
      Rather than pad position. TTI is the single factor that significantly affects
      cardioversion and correlates with energy requirement. The relationship between
      energy requirement and TTI further allows estimation of energy requirements to
      achieve a successfil cardioversion.

PMID- 14711188
TI  - Changes and significance of subtype function of beta-adrenoreceptors in left
      ventricular remodeling of hypertension.
AB  - Changes in the density of myocardium and blood lymphocyte beta-adrenoceptors
      (beta-AR) in left ventricular (LV) geometry have been found in patients with
      essential hypertension (EH). However, it is not known whether intrinsic beta-AR
      subtype function changes during left ventricular remodeling of hypertension. The
      purpose of this study was to further investigate the changes and clinical
      significance of beta-AR subtype function in LV remodeling in patients with EH.
      One hundred and thirty-four men (mean age, 53 years) with EH as defined in the
      Sixth Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure grades 1 to 2 and 40
      normotensives were studied. Based on the echocardiographic LV mass index and
      relative wall thickness, four patterns of LV geometry, ie, normal left ventricle,
      concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were
      identilied. beta-Adrenoreceptor subtype responsiveness was measured by a
      treadmill exercise test (to measure cardiac beta1-adrenoreceptor responsiveness)
      and by Salbutamol injection test (to measure cardiac beta2-adrenoreceptor
      responsiveness) in 134 male patients with EH. Forty normotension subjects were
      also studied as controls. In patients with EH in the groups of concentric
      remodeling, concentric hypertrophy, and eccentric hypertrophy, heart rate in
      response to the treadmill test (peak exercise-resting rate) was significantly
      higher (P < 0.05, P < 0.01. P < 0.01, respectively) than that in the control
      group. In the concentric remodeling and concentric hypertrophy group, the
      chronotropic doses of salbutamol required to increase the heart rate by 30
      beats/min (CD30) were significantly lower (P < 0.05, P < 0.01, respectively) than
      that in the control group. However, in the eccentric hypertrophy group. CD30 was
      higher significantly (P < 0.01) than that in the control group. In the concentric
      remodeling, concentric hypertrophy, and eccentric hypertrophy groups, beta1-AR
      responsiveness significantly increased them in the normotensive group, whereas
      beta2-AR responsiveness significantly increased in the concentric remodeling and
      concentric hypertrophy groups them in the normotensive group, and significantly
      decreased in the eccentric hypertrophy them in the normotensive group. The
      results suggest that non-beta-selective blocker may be beneficial for normal
      morphology, concentric remodeling and concentric hypertrophy, while beta1
      selective blockers may be beneficial for eccentric hypertrophy in patients with
      EH.

PMID- 14711189
TI  - Association of dental status with blood pressure and heart rate in 80-year-old
      Japanese subjects.
AB  - Periodontal disease is one of the main reasons for the loss of teeth in elderly
      subjects, and it has been reported that periodontal disease is a potential risk
      factor for cardiovascular disease. However, little data is available regarding
      the association between dental status and blood pressure or heart rate in elderly
      individuals, particularly in subjects over 80 years old. We studied the cross
      sectional association between dental status and blood pressure or heart rate in
      499 Japanese (195 men and 304 women) who were 80 years old. The subjects were
      divided into 4 groups according to the number of original teeth; ie, edentulous
      (n = 176), 1 to 9 teeth (n = 141), 10 to 19 teeth (n = 109), and more than 20
      teeth (n = 73). Mean systolic and diastolic blood pressures did not differ among
      the groups. However, heart rate decreased from 71.6 and 72.2 /min in the
      edentulous and I to 9 teeth groups, respectively, to 67.3 and 67.4 /min in the 10
      to 19 teeth and more than 20 teeth groups, respectively (test for trend, P =
      0.0008). In multiple regression analysis, the inverse association between the
      number of teeth and heart rate was statistically significant independently of
      other confounding factors. These results are the first to show a close inverse
      relationship between the number of teeth and heart rate in octogenariars,
      although the underlying mechanisms have not been determined.

PMID- 14711190
TI  - Effects of low and high doses of atorvastatin on arterial compliance.
AB  - At the beginning of atherosclerosis before evidence of morphological lesions or
      plaques, vascular distensibility or arterial compliance decreased gradually. This
      endothelial dysfunction is regarded as an early feature of atherosclerosis. In a
      randomized, double-blind study design, group 1 (12 patients; 7 males, 5 females)
      with serum LDL-C levels higher than 170 mg/dL and without any other risk factor
      for atherosclerosis received three months of 20 mg/day atorvastatin treatment
      while group 11 (8 males, 4 females) with the same characteristics received 80
      mg/day. Baseline and posttreatment serum lipid fractions and arterial compliance
      were measured. Arterial compliance was measured noninvasively in the left common
      carotid artery with color Doppler ultrasound. Atorvastatin reduced total
      cholesterol (TC), LDL-C, and triglyceride levels by 32% (P < 0.001), 40.8% (P <
      0.001), and 19% (P < 0.001), respectively, and increased HDL-C by 6.9%, (P =
      0.002) in the first group. In the second group these reductions were 38.5% (P <
      0.001), 46.2% (P < 0.001), and 26.78% (P < 0.001), respectively, and the increase
      in HDL was 7.8% (P = 0.03). It was observed that the decrease in serum TC, LDL-C
      and triglyceride levels were significantly higher in the second group than the
      first group. With atorvastatin, the distensibility coefficient (DC) and
      compliance coefficient (CC) increased from 18.7 +/- 3.4 to 21.3 +/- 2.9 10(-3) x
      kPa(-1) (P < 0.001) and from 0.69 +/- 0.05 to 0.77 +/- 0.03 mm2 x kPa(-1) (P <
      0.001) in the first group while they changed from 18.3 +/- 3.6 to 21.9 +/- 3.0
      10(-3) x kPa(-1) (P < 0.001) and from 0.70 +/- 0.04 to 0.81 +/- 0.01 mm2 x kPa(
      1) (P < 0.001) respectively, in the second group. DC and CC increased in both
      groups, but the differences between the groups were not significant. High doses
      of atorvastatin reduce blood lipid levels more than conventional doses, however,
      the change in compliance is not dose-dependent. As endothelial dysfunction is
      regarded as an early feature of atherosclerosis, there would be no need to
      administer aggressive doses in a patient without any risk factors other than
      hyperlipidemia.

PMID- 14711191
TI  - Inhibitory effects of carvedilol on calcium channels in vascular smooth muscle
      cells.
AB  - Carvedilol has hypotensive effects and inhibits agonist-induced cell
      proliferation of vascular smooth muscle and then prevents vascular remodeling.
      However, the basic mechanisms have not been clarified. We examined the effects of
      carvedilol on [Ca2+]i mobilization and voltage-dependent L-type Ca2+ current
      (ICa.L) in vascular smooth muscle cells, and compared them with metoprolol.
      [Ca2+]i was measured using fura-2 AM and patch clamp techniques in rat embryonic
      aortic smooth muscle cells (A7r5). In the presence of extracellular Ca2+,
      vasopressin and endothelin-1 increased [Ca2+]i due first to the Ca2+ release from
      store sites, and subsequently Ca2+ entry. Carvedilol did not inhibit the Ca2+
      release, but significantly suppressed the sustained rise due to Ca2+ entry
      concentration-dependently. Nilfedipine and nicardipine (10 microM) partly
      inhibited the sustained rise, but carvedilol inhibited it more effectively than
      the Ca2+ channel blockers. Under voltage clamp conditions, carvedilol (0.2-10
      microM) reversibly inhibited the ICa.L concentration-dependently without any
      changes in the current-voltage relationships of ICa.L. Carvedilol shifted the
      steady-state inactivation for ICa.L to more negative potentials and inhibited
      ICa.L in a voltage-dependent manner. In addition, carvedilol did not inhibit Ca2+
      release from store sites induced by thapsigargin, but significantly inhibited the
      sustained rise due to capacitative Ca2+ entry unrelated to ICa.L. In contrast,
      metoprolol did not mimic these effects of carvedilol. These results provide
      evidence that carvedilol inhibits ICa.L and may also inhibit the channels for
      agonist (vasopressin and endothelin-1)-induced Ca2+ entry in vascular smooth
      muscle cells, which might contribute to the vasorelaxing and antiproliferative
      effects of carvedilol.

PMID- 14711192
TI  - Comparison of metoprolol with low, middle and high doses of carvedilol in
      prevention of postinfarction left ventricular remodeling in rats.
AB  - The dose-related beneficial effects of carvedilol on survival in heart failure
      have been verified, however, the effects on left ventricular remodeling (LVRM)
      after acute myocardial infarction (AMI) have not been defined. This experiment
      was designed to compare the effects of low, middle, and high doses of carvedilol
      (LD-car, MD-car, and HD-car) with metoprolol (Meto) in preventing postinfarction
      LVRM in rats. After the left coronary artery was ligated, 177 surviving female SD
      rats were randomized to: (1) AMI (n = 35), (2) LD-car (0.1 mg x kg(-1) x d(-1), n
      = 35), (3) MD-car (1 mg x kg(-1) x d(-1), n = 35), (4) HD-car (10 mg x kg(-1) x
      d(-1), n = 37) and (5) Meto (2 mg x kg(-1) x d(-1), n = 35) groups. A sham
      operated group (n = 16) was also randomly selected. Gastric gavage therapy lasted
      for 4 weeks. After hemodynamic studies, the rat hearts were fixed and
      pathologically analyzed. After exclusion of rats which died or had an infarct
      size < 35% or > 55%, complete data were obtained in 69 rats, comprising AMI (n =
      11), LD-car (n = 11), MD-car (n = 12), HD-car (n = 12), Meto (n = 11) and sham (n
      = 12) groups. There were no significant differences in MI size among the five AMI
      groups (44.5-46.3%, all P > 0.05). Compared with the sham group, left ventricular
      (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal
      thickness (STh) were all significantly increased, while +/- dp/dt was
      significantly decreased in the AMI group (all P < 0.001). Compared with the AMI
      group, heart rate was significantly decreased in all except the LD-car treatment
      groups (P < 0.05-0.01); LVEDP, LVV, LVW, and STh in the four treatment groups
      were also significantly decreased (P < 0.05-0.001) except LVW and STh in the Meto
      group (both P > 0.05)(LVEDP: 14.5 +/- 4.6, 12.1 +/- 2.4, 7.7 +/- 1.9 and 13.0 +/-
      6.7 mmHg vs 24.1 +/- 5.2 mmHg; LVV: 0.82 +/- 0.1, 0.79 +/- 0.1, 0.72 +/- 0.1 and
      0.72 +/- 0.1 mL vs 0.92 +/- 0.1 mL; LVW: 666 +/- 57, 622 +/- 70, 589 +/- 57 and
      699 +/- 78 mg vs 730 +/- 79 mg; STh: 1.14 +/- 0.12, 1.18 +/- 0.21, 1.19 +/- 0.15
      and 1.35 +/- 0.20 mm vs 1.33 +/- 0.29 mm; P < 0.05-0.001); while +/- dp/dt was
      significantly increased in each therapy group (P < 0.05-0.001). There were dose
      effect relations in LVEDP and LVV in the carvedilol groups. The results indicate
      that low, middle and high dose carvedilol has dose-related effects in the
      prevention of postinfarction LVRM with respect to volume expansion and segmental
      hypertrophy in rats, while metoprolol prevents only LV dilatation but not
      hypertrophy.

PMID- 14711193
TI  - Susceptibility to ischemia and reperfusion arrhythmias in myocardial hypertrophy:
      due to flow of injury current?
AB  - Left ventricle (LV) hypertrophy is associated with an increased risk of sudden
      death, which may be due in part to a greater vulnerability to severe ventricular
      arrhythmias. Our objectives were to determine (i) whether pressure overload
      induced LV hypertrophy increases susceptibility to ischemia- and/or reperfusion
      induced ventricular fibrillation (VF), and (ii) whether any increased
      susceptibility is mediated by changes intrinsic to the hypertrophied myocardium.
      LV pressure overload was induced in rats by abdominal aortic constriction (AC),
      while controls received sham-operations (SH). Three weeks after the operation, LV
      weight was 44 +/- 3% greater in AC rats than in SH rats although right ventricle
      (RV) weights were similar. At this time, isolated hearts (n = 12/group) were
      subjected to dual coronary perfusion. Alter 15 minutes of aerobic perfusion,
      either the left or right coronary bed (supplying predominantly LV or RV tissue,
      respectively) was subjected to 7 minutes of zero-flow ischemia and either 5
      minutes of reperfusion (reperfusion study) or 40 minutes of sustained ischemia
      (ischemia study). AC rats exhibited greater susceptibility than SH rats to both
      ischemia- and reperfusion-induced ventricular fibrillation, but only when the
      hypertrophied LV was subjected to ischemia. The increased susceptibility to
      arrhythmias was not entirely due to a larger ischemic zone, indicating that
      intrinsic changes within hypertrophied myocarium played a role in
      arrhythmogenesis.

PMID- 14711194
TI  - Diltiazem facilitates inactivation of single L-type calcium channels in guinea
      pig ventricular myocytes.
AB  - Diltiazem is a benzothiazepine Ca2+ channel blocker used clinically for its
      antihypertensive and antiarrhythmic effects. We studied the mechanism of
      diltiazem blockade by recording L-type Ca2+ channel currents from cell-attached
      patches in isolated guinea pig ventricular myocytes using Ba2+ as the charge
      carrier. With diltiazem (200 microM) in the superfusate, multichannel currents
      showed a use-dependent decline in amplitude reflecting reductions in the numbers
      of superpositions of channel openings. Analysis of single-channel currents
      revealed that both open and closed times were little affected by diltiazem (50
      and 100 microM). However, the rate of decay of the averaged current during 150-ms
      depolarization steps was significantly accelerated and the open state probability
      in current containing-sweeps was significantly decreased by diltiazem, suggesting
      that the drug accelerates transition from the activated state to the inactivated
      state. The effect of diltiazem on the slow gating process was studied by
      repetitively applying 500-1000 step pulses at selected holding potentials.
      Decreased channel availability by diltiazem was reflected by the increasing
      number of blank sweeps per run at depolarized holding potentials. These results
      suggest that diltiazem reduces Ca2+ influx by accelerating inactivation during
      action potentials, and that the use-dependent blockade is due to increases in the
      number of channels in a sustained closed state.

PMID- 14711195
TI  - Congenital absence of the left circumflex coronary artery.
AB  - We report a rare case of congenital coronary artery anomaly with recurrent chest
      pain. A 44-year-old Taiwanese female patient presented with exertional chest pain
      that had lasted for 2 years. An electrocardiogram showed right axis deviation and
      an rS pattern in leads I and aVL, and an exercise stress test was inconclusive. A
      thallium-201 myocardial perfusion study revealed perfusion defects in the septal
      and inferior walls which normalized in the delayed imaging. Coronary angiography
      revealed the absence of a left circumflex coronary artery and a superdominant
      right coronary artery with terminal branches supplying the left ventricular
      inferior and posterolateral walls. An aortogram revealed no evidence of the
      existence of a left circumflex coronary artery. Administration of nitrates and
      calcium antagonists could not ameliorate her symptoms, but she remained stable
      during ordinary activity. In young premenopausal female patients who present with
      symptoms suggestive of angina pectoris and a positive stress test, congenital
      anomaly of the coronary artery should be considered and an angiographic study
      should be performed.

PMID- 14711196
TI  - Coronary artery spasm discovered in thorough examination of perioperative VT in a
      26-year-old Japanese male.
AB  - We thoroughly examined a 26-year-old Japanese male who experienced perioperative
      ventricular tachycardia. After inhaling sevoflurane, his nasal cavity was soaked
      with 1:100,000 epinephrine and he was intubated through the nose. Junctional
      tachycardia occurred five minutes after intubation, changing to ventricular
      tachycardia. Six-time cardioversion was required to stop the ventricular
      tachycardia. Echocardiography immediately following the event showed diffuse
      hypokinesis, and an electrocardiogram showed an inversion of T waves in II, III,
      aVF and V4-6. Both returned to normal within a few days. Tl scintigraphy revealed
      a normal perfusion image. Coronary angiography showed a normal coronary, but an
      injection of acetylcholine induced vasospasm in the right coronary artery.
      Examination of left ventricular tissue yielded no specific findings. During
      electrophysiological tests, ventricular tachycardia could not be induced even in
      the presence of isoprenaline. This is a very young case to elicit vasospasm in
      the coronary artery with no underlying heart disease. Although the relationship
      between perioperative ventricular tachycardia and coronary spasm is unknown,
      cardiac events can occur during anesthesia in young and low-risk patients.

PMID- 14711197
TI  - Improvement of ventricular arrhythmia by octreotide treatment in acromegalic
      cardiomyopathy.
AB  - We report a case of acromegalic cardiomyopathy in a 46-year-old Japanese man with
      pituitary adenoma. Increased secretion of growth hormone and insulin-like growth
      factor I were detected. He had left ventricular hypertrophy, impaired cardiac
      function, and frequent ventricular premature complexes. After 2-month treatment
      with octreotide, a long-acting somatostatin analogue, levels of both hormones
      were decreased. At the same time, left ventricular hypertrophy (intraventricular
      septal thickness: 22.5 to 17.8 mm), cardiac function (ejection fraction: 38 to
      50%), and frequency of ventricular premature complexes (17,249 to 2,882 beats a
      day) were improved. Transsphenoidal surgery was then safely performed. Treatment
      with octreotide is thought to have some effect on improvement of ventricular
      arrhythmia in acromegalic heart.

PMID- 14711198
TI  - Electrocardiographic J wave as a result of hypercalcemia aggravated by thiazide
      diuretics in a case of primary hyperparathyroidism.
AB  - Electrocardiographically, the QT interval is shortened, ST segment is depressed,
      and T wave becomes negative in hypercalcemia. The use of diuretics in cases with
      hyperparathyroidism decreases the excretion of calcium, causes changes in bone
      calcium turnover and parathyroid hormone activity, and forms hypercalcemia. A 67
      year-old Turkish female patient in whom we electrocardiographically observed a J
      wave is presented as a hypercalcemic case with primary, hyperparathyroidism
      aggravated by the use of a thiazide diuretic.

PMID- 14711272
TI  - Simvastatin reduced mortality and vascular events in diabetes mellitus.

PMID- 14711273
TI  - Acarbose reduced the risk for cardiovascular disease and hypertension in impaired
      glucose tolerance.

PMID- 14711274
TI  - Review: Low-dose diuretics are the best first-line antihypertensive therapy.

PMID- 14711275
TI  - Review: lower dose combination antihypertensive therapy is preferable to standard
      dose single drug therapy.

PMID- 14711276
TI  - Carvedilol was more effective than metoprolol tartrate for lowering mortality in
      chronic heart failure.

PMID- 14711277
TI  - Review: amiodarone is effective for converting atrial fibrillation to sinus
      rhythm.

PMID- 14711278
TI  - Review: comprehensive occupational therapy interventions improve outcomes after
      stroke.

PMID- 14711279
TI  - An intervention to treat depression and increase social support did not prolong
      event-free survival in coronary heart disease.

PMID- 14711280
TI  - Ticlopidine was not better than aspirin for preventing recurrent stroke in
      African-Americans with noncardioembolic ischemic stroke.

PMID- 14711281
TI  - Dalteparin reduced recurrent venous thromboembolism more than oral
      anticoagulation in patients with cancer.

PMID- 14711282
TI  - A scheduled second endoscopy 16 to 24 hours after initial endoscopic hemostasis
      reduced recurrent peptic ulcer bleeding.

PMID- 14711283
TI  - Review: regular inhaled short-acting beta2-agonists improve lung function in
      stable chronic obstructive pulmonary disease.

PMID- 14711285
TI  - Inhaled corticosteroids was safely stepped down in chronic, stable asthma.

PMID- 14711284
TI  - Review: omalizumab reduces asthma exacerbations and daily steroid use.

PMID- 14711287
TI  - Intravenous N-acetylcysteine prevented contrast nephropathy.

PMID- 14711286
TI  - Review: anticholinergic drugs improve motor function and disability in Parkinson
      disease.

PMID- 14711288
TI  - Therapeutic knee taping improved pain and disability in osteoarthritis of the
      knee.

PMID- 14711289
TI  - Review: the cosyntropin-stimulation test has limited value for detecting and
      excluding adrenal insufficiency.

PMID- 14711290
TI  - Diabetes and other comorbidities were associated with a poor outcome in the
      severe acute respiratory syndrome.

PMID- 14711291
TI  - 34% mortality rate from SARS in critically ill patients at 28 days in Toronto.

PMID- 14711292
TI  - 37% mortality rate from SARS in critically ill patients at 28 days in Singapore.

PMID- 14711293
TI  - A nurse-facilitator intervention improved the use of beta-blockers in outpatients
      with stable congestive heart failure.

PMID- 14711294
TI  - Noninvasive ventilation was cost-effective for reducing in-hospital mortality in
      COPD.

PMID- 14711295
TI  - Review: absence of somatosensory evoked potentials after onset of coma has a high
      specificity for predicting nonawakening.

PMID- 14711296
TI  - A prediction rule identified patients with atrial fibrillation at low risk for
      stroke while taking aspirin.

PMID- 14711297
TI  - Patients at the center: in our practice, and in our use of language.

PMID- 14711298
TI  - A win-win proposition: help us to build better evidence-based information systems
      for you.

PMID- 14711299
TI  - Discovery of the first N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphan to
      possess highly potent and selective opioid delta receptor antagonist activity.
AB  - A structurally novel opioid delta receptor selective antagonist has been
      identified. This compound, (+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2
      azabicyclo[3.3.1]non-7-yl-(1-phenyl-1-cyclopentane)carboxamide [(+)-KF4, (+)-4],
      showed a K(e) value of 0.15 nM in the [(35)S]GTPgammaS functional assay. (+)-KF4
      is also a delta inverse agonist with an IC(50) value of 1.8 nM. To our knowledge,
      this is the first potent and selective delta opioid receptor antagonist from the
      5-phenylmorphan class of opioids.

PMID- 14711300
TI  - Discovery of a bulky 2-tert-butyl group containing primaquine analogue that
      exhibits potent blood-schizontocidal antimalarial activities and complete
      elimination of methemoglobin toxicity.
AB  - To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two
      compounds, where C-2 position of the antimalarial drug primaquine is blocked by
      metabolically stable bulky alkyl group are synthesized. Compound 2 [R =
      C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against
      P. berghei and highly virulent multidrug-resistant P. yoelii nigeriensis strain
      in vivo. Compound 2 was also evaluated for methemoglobin (MetHb) toxicity. This
      study describes the discovery of a highly potent blood-schizontocidal
      antimalarial analogue 2, completely devoid of MetHb toxicity.

PMID- 14711301
TI  - Triacylglycerols based on 2-(N-tert-butoxycarbonylamino)oleic acid are potent
      inhibitors of pancreatic lipase.
AB  - A novel class of potent human pancreatic lipase (HPL) inhibitors was developed.
      Triacylglycerol analogues containing 2-(N-tert-butoxycarbonylamino) fatty acids
      were synthesized, and their ability to form stable films at the air/water
      interface was studied. The inhibition of human digestive lipases by the compounds
      synthesized was studied by the monolayer technique, and the triesters of glycerol
      and 2-methylglycerol with 2-(N-tert-butoxycarbonylamino)oleic acid were found to
      be potent inhibitors of HPL.

PMID- 14711302
TI  - Enantioselective synthesis and biological activity of (3S,4R)- and (3S,4S)-3
      hydroxy-4-hydroxymethyl- 4-butanolides in relation to PGE2.
AB  - Compounds 9 and 13 were synthesized, and their structures and stereochemistry
      were elucidated by spectroscopic methods. In competition binding experiments,
      specific [(3)H]-PGE(2) binding was significantly displaced by compound 9 and, to
      a lesser extent, by 13, in a dose-dependent manner. The biological properties of
      compound 9 were studied on HL-60 cells, and several effects were found related to
      those of PGE(2). Compound 9 increases c-fos mRNA level as does PGE(2) and
      antagonizes TPA-induced terminal differentiation.

PMID- 14711303
TI  - Synthesis, monoamine transporter binding properties, and behavioral pharmacology
      of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5
      yl)tropanes.
AB  - Several 3beta-(substituted phenyl)-2beta-(3-substituted isoxazol-5-yl)tropanes
      (3a-t) were evaluated for their ability to inhibit radioligand binding at the
      DAT, 5-HTT, and NET as well as in gross observation and locomotor activity in
      mice and in rats trained to discriminate cocaine. All compounds showed high
      affinity for the DAT. The IC(50) values ranged from 0.5 to 26 nM. With the
      exception of 3e and 3f, which have no substituent on the 2beta-(1,2-isoxazole)
      ring, all compounds were selective for the DAT relative to the 5-HTT and NET. No
      compound showed death when dosed at 100 mg/kg; however, most compounds did show
      signs typical of dopamine activity. The ED(50) values for 2beta-(1,2-isoxazoles)
      that caused locomotor stimulation ranged from 0.2 to 12.8 mg/kg. Most compounds
      showed slower on-set and longer duration of action relative to cocaine.
      Surprisingly, 3beta-(4-methylphenyl)-2beta-[3-(4'-chlorophenyl)isoxazol-5
      yl]tropane (3p) and 3beta-(4-methylphenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5
      yl]tropane (3r) did not produce significant increases in locomotor activity. In
      the cocaine discrimination test, all analogues showed full or at least 50%
      generalization with the exception of 3p, which did not show generalization.
      Importantly, both the locomotor activity and the cocaine discrimination
      ED(50)values were correlated with the DAT binding but not 5-HTT and NET binding.
      This provides further support for the dopamine hypothesis of cocaine abuse. High
      DAT affinity and selectivity, increased locomotor activity with slow onset and
      long duration of action, and generalization to cocaine shown by the 3beta
      (substituted phenyl)-2beta-(3-substituted isoxazol-5-yl)tropanes are properties
      thought necessary for a pharmacotherapy for treating cocaine abuse.

PMID- 14711304
TI  - Identification of novel binding interactions in the development of potent,
      selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural
      analysis, and SAR of N-phenyl amide 6-substitution.
AB  - The preparation and assessment of biological activity of 6-substituted 2
      naphthamidine inhibitors of the serine protease urokinase plasminogen activator
      (uPA, or urokinase) is described. 2-Naphthamidine was chosen as a starting point
      based on synthetic considerations and on modeling of substituent vectors. Phenyl
      amides at the 6-position were found to improve binding; replacement of the amide
      with other two-atom linkers proved ineffective. The phenyl group itself is
      situated near the S1' subsite; substitutions off of the phenyl group accessed S1'
      and other distant binding regions. Three new points of interaction were defined
      and explored through ring substitution. A solvent-exposed salt bridge with the
      Asp60A carboxylate was formed using a 4-alkylamino group, improving affinity to
      K(i) = 40 nM. Inhibitors also accessed two hydrophobic regions. One interaction
      is characterized by a tight hydrophobic fit made with a small dimple largely
      defined by His57 and His99; a weaker, less specific interaction involves alkyl
      groups reaching into the broad prime-side protein binding region near Val41 and
      the Cys42-Cys58 disulfide, displacing water molecules and leading to small gains
      in activity. Many inhibitors accessed two of these three regions. Affinities
      range as low as K(i) = 6 nM, and many compounds had K(i) < 100 nM, while moderate
      to excellent selectivity was gained versus four of five members of a panel of
      relevant serine proteases. Also, some selectivity against trypsin was generated
      via the interaction with Asp60A. X-ray structures of many of these compounds were
      used to inform our inhibitor design and to increase our understanding of key
      interactions. In combination with our exploration of 8-substitution patterns, we
      have identified a number of novel binding interactions for uPA inhibitors.

PMID- 14711305
TI  - Evaluation of P1'-diversified phosphinic peptides leads to the development of
      highly selective inhibitors of MMP-11.
AB  - Phosphinic peptides were previously reported to be potent inhibitors of several
      matrixins (MMPs). To identify more selective inhibitors of MMP-11, a matrixin
      overexpressed in breast cancer, a series of phosphinic pseudopeptides bearing a
      variety of P(1)'-side chains has been synthesized, by parallel diversification of
      a phosphinic template. The potencies of these compounds were evaluated against a
      set of seven MMPs (MMP-2, MMP-7, MMP-8, MMP-9, MMP-11, MMP-13, and MMP-14). The
      chemical strategy applied led to the identification of several phosphinic
      inhibitors displaying high selectivity toward MMP-11. One of the most selective
      inhibitors of MMP-11 in this series, compound 22, exhibits a K(i) value of 0.23
      microM toward MMP-11, while its potency toward the other MMPs tested is 2 orders
      of magnitude lower. This remarkable selectivity may rely on interactions of the
      P(1)'-side chain atoms of these inhibitors with residues located at the entrance
      of the S(1)'-cavity of MMP-11. The design of inhibitors able to interact with
      residues located at the entrance of MMPs' S(1)'-cavity might represent an
      alternative strategy to identify selective inhibitors that will fully
      differentiate one MMP among the others.

PMID- 14711306
TI  - Structural interaction fingerprint (SIFt): a novel method for analyzing three
      dimensional protein-ligand binding interactions.
AB  - Representing and understanding the three-dimensional (3D) structural information
      of protein-ligand complexes is a critical step in the rational drug discovery
      process. Traditional analysis methods are proving inadequate and inefficient in
      dealing with the massive amount of structural information being generated from X
      ray crystallography, NMR, and in silico approaches such as structure-based
      docking experiments. Here, we present SIFt (structural interaction fingerprint),
      a novel method for representing and analyzing 3D protein-ligand binding
      interactions. Key to this approach is the generation of an interaction
      fingerprint that translates 3D structural binding information from a protein
      ligand complex into a one-dimensional binary string. Each fingerprint represents
      the "structural interaction profile" of the complex that can be used to organize,
      analyze, and visualize the rich amount of information encoded in ligand-receptor
      complexes and also to assist database mining. We have applied SIFt to tackle
      three common tasks in structure-based drug design. The first involved the
      analysis and organization of a typical set of results generated from a docking
      study. Using SIFt, docking poses with similar binding modes were identified,
      clustered, and subsequently compared with conventional scoring function
      information. A second application of SIFt was to analyze approximately 90 known X
      ray crystal structures of protein kinase-inhibitor complexes obtained from the
      Protein Databank. Using SIFt, we were able to organize the structures and reveal
      striking similarities and diversity between their small molecule binding
      interactions. Finally, we have shown how SIFt can be used as an effective
      molecular filter during the virtual chemical library screening process to select
      molecules with desirable binding mode(s) and/or desirable interaction patterns
      with the protein target. In summary, SIFt shows promise to fully leverage the
      wealth of information being generated in rational drug design.

PMID- 14711307
TI  - Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial
      activities and binding affinities to wild type and mutant dihydrofolate
      reductases from Plasmodium falciparum.
AB  - The resistance to pyrimethamine (PYR) of Plasmodium falciparum arising from
      mutation at position 108 of dihydrofolate reductase (pfDHFR) from serine to
      asparagine (S108N) is due to steric interaction between the bulky side chain of
      N108 and Cl atom of the 5-p-Cl aryl group of PYR, which consequently resulted in
      the reduction in binding affinity between the enzyme and inhibitor. Molecular
      modeling suggested that the flexible antifolate, such as trimethoprim (TMP)
      derivatives, could avoid this steric constraint and should be considered as new,
      potentially effective compounds. The hydrophobic interaction between the side
      chain of inhibitor and the active site of the enzyme around position 108 was
      enhanced by the introduction of a longer and more hydrophobic side chain on TMP's
      5-benzyl moiety. The prepared compounds, especially those bearing aromatic
      substituents, exhibited better binding affinities to both wild type and mutant
      enzymes than the parent compound. Binding affinities of these compounds
      correlated well with their antimalarial activities against both wild type and
      resistant parasites. Molecular modeling of the binding of such compounds with
      pfDHFR also supported the experimental data and clearly showed that aromatic
      substituents play an important role in enhancing binding affinity. In addition,
      some compounds with 6-alkyl substituents showed relatively less decrease in
      binding constants with the mutant enzymes and relatively good antimalarial
      activities against the parasites bearing the mutant enzymes.

PMID- 14711308
TI  - Diflunisal analogues stabilize the native state of transthyretin. Potent
      inhibition of amyloidogenesis.
AB  - Analogues of diflunisal, an FDA-approved nonsteroidal antiinflammatory drug
      (NSAID), were synthesized and evaluated as inhibitors of transthyretin (TTR)
      aggregation, including amyloid fibril formation. High inhibitory activity was
      observed for 26 of the compounds. Of those, eight exhibited excellent binding
      selectivity for TTR in human plasma (binding stoichiometry >0.50, with a
      theoretical maximum of 2.0 inhibitors bound per TTR tetramer). Biophysical
      studies reveal that these eight inhibitors dramatically slow tetramer
      dissociation (the rate-determining step of amyloidogenesis) over a duration of
      168 h. This appears to be achieved through ground-state stabilization, which
      raises the kinetic barrier for tetramer dissociation. Kinetic stabilization of WT
      TTR by these eight inhibitors is further substantiated by the decreasing rate of
      amyloid fibril formation as a function of increasing inhibitor concentration (pH
      4.4). X-ray cocrystal structures of the TTR.18(2) and TTR.20(2) complexes reveal
      that 18 and 20 bind in opposite orientations in the TTR binding site. Moving the
      fluorines from the meta positions in 18 to the ortho positions in 20 reverses the
      binding orientation, allowing the hydrophilic aromatic ring of 20 to orient in
      the outer binding pocket where the carboxylate engages in favorable electrostatic
      interactions with the epsilon-ammonium groups of Lys 15 and 15'. The hydrophilic
      aryl ring of 18 occupies the inner binding pocket, with the carboxylate
      positioned to hydrogen bond to the serine 117 and 117' residues. Diflunisal
      itself appears to occupy both orientations based on the electron density in the
      TTR.1(2) structure. Structure-activity relationships reveal that para-carboxylate
      substitution on the hydrophilic ring and dihalogen substitution on the
      hydrophobic ring afford the most active TTR amyloid inhibitors.

PMID- 14711310
TI  - Application of CoMFA and CoMSIA 3D-QSAR and docking studies in optimization of
      mercaptobenzenesulfonamides as HIV-1 integrase inhibitors.
AB  - An essential step in the HIV life cycle is integration of the viral DNA into the
      host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase
      (IN). HIV-1 IN is an important and validated target, and the drugs that
      selectively inhibit this enzyme, when used in combination with reverse
      transcriptase (RT) and protease (PR) inhibitors, are believed to be highly
      effective in suppressing the viral replication. IN catalyzes two discrete
      enzymatic processes referred to as 3' processing and DNA strand transfer. As a
      part of a study to optimize new lead molecules we previously identified from a
      series of 2-mercaptobenzenesulfonamides (MBSAs), we applied three-dimensional
      quantitative structure-activity relationship methods, comparative molecular field
      analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA)
      to training sets of up to 66 compounds. Two different conformational templates
      were used: Conf-d, obtained from docking into the HIV-1 IN active site and Conf-s
      obtained by a systematic conformational search, using lead compounds 1 and 14,
      respectively. Reliable models of good predictive power were obtained after
      removal of compounds with high residuals. The Conf-s models tended to perform
      better than the Conf-d models. Cross-validated coefficients (q(2)) of up to 0.719
      (strand transfer CoMSIA, Conf-s) regression coefficients (r(2)) of up to 0.932
      (strand transfer CoMSIA, Conf-d) were obtained, with the number of partial least
      squares (PLS) components varying from 3 to 6, and the number of outliers being 4
      in most of the models. Because all biological data were determined under exactly
      the same conditions using the same enzyme preparation, our predictive models are
      promising for drug optimization. Therefore, these results combined with docking
      studies were used to guide the rational design of new inhibitors. Further
      synthesis of 12 new analogues was undertaken, and these were used as a test set
      for validation of the quantitative structure-activity relationship (QSAR) models.
      For compounds with closely related structures, binding energies given by the
      FlexX scoring function correlated with HIV-1 IN inhibitory activity.

PMID- 14711309
TI  - Quantitative structure-activity relationships for gammadelta T cell activation by
      bisphosphonates.
AB  - gammadelta T cells are the first line of defense against many infectious
      organisms and are also involved in tumor cell surveillance and killing. They are
      stimulated by a broad range of small, phosphorus-containing antigens
      (phosphoantigens) as well as by the bisphosphonates commonly used in bone
      resorption therapy, such as pamidronate and risedronate. Here, we report the
      activation of gammadelta T cells by a broad range of bisphosphonates and develop
      a pharmacophore model for gammadelta T cell activation, in addition to using a
      comparative molecular similarity index analysis (CoMSIA) approach to make
      quantitative relationships between gammadelta T cell activation by
      bisphosphonates and their three-dimensional structures. The CoMSIA analyses
      yielded R(2) values of approximately 0.8-0.9 and q(2) values of approximately 0.5
      0.6 for a training set of 45 compounds. Using an external test set, the
      activities (IC(50) values) of 16 compounds were predicted within a factor of 4.5,
      on average. The CoMSIA fields consisted of approximately 40% hydrophobic,
      approximately 40% electrostatic, and approximately 20% steric interactions. Since
      bisphosphonates are known to be potent, nanomolar inhibitors of the
      mevalonate/isoprene pathway enzyme farnesyl pyrophosphate synthase (FPPS), we
      also compared the pharmacophores for gammadelta T cell activation with those for
      FPPS inhibition, using the Catalyst program. The pharmacophores for gammadelta T
      cell activation and FPPS inhibition both consisted of two negative ionizable
      groups, a positive charge feature and an endocyclic carbon feature, all having
      very similar spatial dispositions. In addition, the CoMSIA fields were quite
      similar to those found for FPPS inhibition by bisphosphonates. The activities of
      the bisphosphonates in gammadelta T cell activation were highly correlated with
      their activities in FPPS inhibition: R = 0.88, p = 0.002, versus a human
      recombinant FPPS (N = 9 compounds); R = 0.82, p < 0.0001, for an expressed
      Leishmania major FPPS (N = 45 compounds). The bisphosphonate gammadelta T cell
      activation pharmacophore differs considerably, however, from that reported
      previously for gammadelta T cell activation by phosphoantigens (Gossman, W.;
      Oldfield, E. J. Med. Chem. 2002, 45, 4868-4874), suggesting different primary
      targets for the two classes of compounds. The ability to quite accurately predict
      the activity of bisphosphonates as gammadelta T cell activators by using 3D QSAR
      techniques can be expected to help facilitate the design of additional
      bisphosphonates for potential use in immunotherapy.

PMID- 14711311
TI  - Synthesis and structure-activity relationship for a novel class of potent and
      selective carbamoyl-triazole based inhibitors of hormone sensitive lipase.
AB  - The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in
      regulating fatty acid metabolism makes it an interesting pharmacological target
      for the treatment of insulin resistant and dyslipidemic disorders where a
      decrease in delivery of fatty acids to the circulation is desirable, e.g., in
      individuals with type 2 diabetes, metabolic syndrome, or impaired glucose
      tolerance. On the basis of a lead structure from high throughput screening, we
      have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As
      part of the lead optimization program, four new classes of carbamoyl-triazoles
      were synthesized and tested with respect to potency, efficacy and selectivity.
      Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL
      inhibitors. These compounds do not inhibit other hydrolases such as hepatic
      lipase, lipoprotein lipase, pancreatic lipase, and butyrylcholine esterase.
      However, the inhibitors 4b and 4g with IC(50) values for HSL of 0.17 and 0.25
      microM, respectively, were the only inhibitors selective against acetylcholine
      esterase. A reversible pseudosubstrate inhibition mechanism is proposed for this
      class of inhibitors.

PMID- 14711312
TI  - Semisynthetic macrolide antibacterials derived from tylosin. Synthesis and
      structure-activity relationships of novel desmycosin analogues.
AB  - A series of 20-O-substituted and 3,20-di-O-substituted derivatives of desmycosin
      were synthesized and their biological properties were evaluated. In particular,
      we have synthesized numerous side chain modified analogues of desmycosin as well
      as some analogues possessing a combination of modified side chain and alternative
      C-3 substituents. Thus, alpha,beta-unsaturated analogues of desmycosin (2),
      tylosin (1), 10,11,12,13-tetrahydrotylosin (11), and 2,3-didehydrodesmycosin (13)
      were prepared from the corresponding aldehydes by a Wittig reaction with the
      stabilized ylides (a-d), generating a trans-double bond, followed by modified
      Pfitzner-Moffat oxidation of the C-3 hydroxyl group. To evaluate the importance
      of the C-3 position of desmycosin for biological activity, the C-3 substituted
      derivatives were synthesized by a standard sequence of protective group chemistry
      followed by Wittig reaction and esterification as the key steps. For the
      attachment of the C-3 ester functionality, a mixed anhydride protocol was
      adopted. Reaction proceeded smoothly to give corresponding esters in yields
      ranging from 70 to 80%. Base- and acid-catalyzed rearrangement products including
      desmycosin 8,20-aldols (24a and 24b) and desmycosin 3,19-aldol (25) are also
      described. Parallel array synthesis and purification techniques allowed for the
      rapid exploration of structure-activity relationships within this class and for
      the improvement in potency. In vitro evaluation of these derivatives demonstrated
      good antimicrobial activity against Gram-positive bacteria for most of the
      compounds. The present derivatives of 16-membered macrolides were active against
      MLS(B)-resistant strains that were inducibly resistant, but not those
      constitutively resistant to erythromycin.

PMID- 14711313
TI  - Design and synthesis of peptidomimetic protein farnesyltransferase inhibitors as
      anti-Trypanosoma brucei agents.
AB  - On the basis of the structure of the CVIM tetrapeptide substrate of mammalian
      protein farnesyltransferase, a series of imidazole-containing peptidomimetics was
      designed and synthesized, and their inhibition activity against Trypanosoma
      brucei protein farnesyltransferase (TbPFT) was evaluated. Peptidomimetics where
      the 5-position of the imidazole ring was linked to the hydrophobic scaffold
      showed over 70% inhibition activity at 50 nM in the enzyme assay, whereas the
      corresponding C-4 regioisomers were less potent. The ester prodrug 23 was found
      to be a potent inhibitor against cultured Trypanosoma brucei brucei and
      Trypanosoma brucei rhodesiense cells with ED(50) values of 0.025 and 0.0026
      microM, respectively. Furthermore, introducing a second imidazole group into 23
      led to 31, which showed the highest inhibition activity against the parasite with
      an ED(50) of 0.0015 microM. The potency of the TbPFT inhibitors and the
      cytotoxicity of the corresponding esters to T. brucei cells were shown to be
      highly correlated. These studies validate TbPFT as a target for the development
      of novel therapeutics against African sleeping sickness.

PMID- 14711314
TI  - Synthesis and opioid activity of side-chain-to-side-chain cyclic dynorphin A-(1
      11) amide analogues cyclized between positions 2 and 5. 1. Substitutions in
      position 3.
AB  - cyclo[d-Asp(2),Dap(5)]Dyn A-(1-13)NH(2) (Dap, 2,3-diaminopropionic acid; Dyn A,
      dynorphin A), synthesized previously in our laboratory, showed sub-nanomolar
      affinity for kappa opioid receptors and potent agonist activity in the guinea pig
      ileum assay (Arttamangkul et al., J. Med. Chem. 1995, 38, 2410-2417). Various
      modifications were made in position 3 of cyclo[d-Asp(2),Dap(5)]Dyn A-(1-11)NH(2)
      that could influence the opioid receptor affinity, selectivity, and/or efficacy
      of this peptide. An optimized orthogonal synthetic strategy was developed for the
      synthesis of these cyclic peptides in which the final peptides could be cleaved
      from the solid support with trifluoroacetic acid. Substitutions of Gly(3) by Ala,
      d-Ala, Trp, and d-Trp in cyclo[d-Asp(2),Dap(5)]Dyn A-(1-11)NH(2) and its linear
      counterpart [d-Asp(2),Dap(5)]Dyn A-(1-11)NH(2) were generally well tolerated by
      both kappa and micro opioid receptors. Despite differences in the size and
      stereochemistry of the substitutions, most of the peptides (except for cyclo[d
      Asp(2),Pro(3),Dap(5)]Dyn A-(1-11)NH(2) and [d-Asp(2),d-Ala(3), Dap(5)]Dyn A-(1
      11)NH(2)) exhibited low nanomolar affinity for both kappa (K(i) = 0.21 to 2.2 nM)
      and micro (K(i) = 0.22 to 7.27 nM) opioid receptors. All of the 3-substituted
      cyclic and linear analogues synthesized showed reduced affinity for delta opioid
      receptors. Incorporation of d-Ala at position 3 of cyclo[d-Asp(2),Dap(5)]Dyn A-(1
      11)NH(2) exhibited 2-fold higher kappa opioid receptor affinity and 16-fold
      higher selectivity for kappa over micro opioid receptors than the parent cyclic
      peptide. In contrast, substitution of Ala at position 3 resulted in an analogue
      with 2.4-fold lower affinity and very low preference for kappa over micro opioid
      receptors. The Trp and d-Trp cyclic and linear analogues exhibited similar
      nanomolar affinities for kappa opioid receptors. cyclo[d-Asp(2),Pro(3),Dap(5)]Dyn
      A-(1-11)NH(2) showed the largest decreases in affinity for all three opioid
      receptors compared to the parent cyclic peptide. Except for cyclo[d-Asp(2),
      Pro(3),Dap(5)]Dyn A-(1-11)NH(2), which was a partial agonist, all of the cyclic
      peptides exhibited full agonist activity in the adenylyl cyclase assay using
      cloned kappa opioid receptors.

PMID- 14711315
TI  - (2S,1'S,2'R,3'R)-2-(2'-Carboxy-3'-hydroxymethylcyclopropyl) glycine is a highly
      potent group 2 and 3 metabotropic glutamate receptor agonist with oral activity.
AB  - The asymmetric synthesis and biological activity of (2S,1'S,2'R,3'R)-2-(2'
      carboxy-3'-hydroxymethylcyclopropyl) glycine ((+)-3) is described. This novel C
      3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3
      mGluR agonist that has proven to be orally active in both fear potentiated
      startle (animal model for anxiety) and PCP-induced motor activation (animal model
      for psychosis) assays in rats.

PMID- 14711316
TI  - Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone
      deacetylase inhibitors.
AB  - Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty
      acids exhibit the least potency, with IC(50) in the millimolar range. We
      rationalized that this weak potency was, in part, attributable to their inability
      to access the zinc cation in the HDAC active-site pocket, which is pivotal to the
      deacetylation catalysis. We thus explored the structural optimization of
      valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with
      Zn(2+)-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic
      omega-amino acid linkers. This strategy has led to a novel class of Zn(2+)
      chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees
      of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N
      hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in
      inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the
      submicromolar level showed reduced cell proliferation accompanied by histone
      hyperacetylation and elevated p21(WAF/CIP1) expression, which are hallmark
      features associated with intracellular HDAC inhibition.

PMID- 14711317
TI  - DNA-targeted 1,2,4-benzotriazine 1,4-dioxides: potent analogues of the hypoxia
      selective cytotoxin tirapazamine.
AB  - Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive
      hypoxia-selective cytotoxin, currently in phase II/III clinical trials in
      combination with radiotherapy and with cisplatin-based chemotherapy. We have
      prepared a series of 1,2,4-benzotriazine 1,4-dioxide (BTO) analogues of TPZ where
      a DNA-targeting chromophore is attached at the 3-position via a flexible linker.
      DNA binding affinity was modified through variation of the chromophore or the
      pK(a) of the linker chain. The association constants (K(DNA)) for calf thymus DNA
      ranged from 1 x 10(2) to 5.6 x 10(5) M(-1) (ionic strength of 0.01 M). DNA
      binding affinity was dependent on the presence of a positive charge, either in
      the linker chain or in the chromophore, and (for a series of 4-acridine
      carboxamide chromophore analogues) correlated strongly with linker chain pK(a).
      The efficacy of these BTOs in killing aerobic and hypoxic mouse SCCVII tumor
      cells in vitro was determined by clonogenic survival. Cytotoxicity was measured
      as the concentration required to reduce plating efficiency to 10% of controls
      (C(10)), and the hypoxic cytotoxicity ratio (HCR) for each BTO was calculated as
      C(10)(aerobic)/C(10)(hypoxic). BTOs bearing a positive charge showed increased
      hypoxic cytotoxicity (1.5-56-fold) compared to TPZ and mostly modest HCRs (8-51),
      but some excellent (>167 and 400) values. There was a strong correlation between
      K(DNA) and hypoxic cytotoxicity but no correlation between K(DNA) and HCR.
      Cytotoxicity in HT-29 human colon carcinoma cells, determined using IC(50)
      assays, showed similar relationships with a correlation between K(DNA) and
      hypoxic cytotoxicity but no correlation between K(DNA) and HCR. In this cell
      line, a higher proportion of compounds (7 of 11) had HCRs greater than or equal
      to that of TPZ. The data confirm that DNA targeting is a useful concept for
      increasing potency while maintaining hypoxic selectivity and provide a direction
      for the further development of DNA-targeted analogues of TPZ.

PMID- 14711319
TI  - Regulatory pathways for developing market vaccines.

PMID- 14711318
TI  - Restriction of a peptide turn conformation and conformational analysis of
      guanidino group using arginine-proline fused amino acids: application to mini
      atrial natriuretic peptide on binding to the receptor.
AB  - Compounds (2S,4S)- and (2S,4R)-4-(2'-guanidinoethyl)proline have been synthesized
      as a conformationally restricted arginine. Their backbones fit the i + 1 position
      in a turn, and the side chains are restricted compared to that of arginine. These
      analogues were incorporated into mini atrial natriuretic polypeptide, which has
      an important turnlike conformation at Gly(6)-Arg(7)()-Met(8)-Asp(9). Structural
      analysis revealed that the size of the conformational space of Arg(7) on binding
      to the receptor was approximately one-third of the entire conformational space.

PMID- 14711322
TI  - An overview of vaccination against infectious disease in children in 2003.

PMID- 14711323
TI  - Immune intervention in HPV infections: current progress and future developments.

PMID- 14711324
TI  - Heptavalent pneumococcal conjugate vaccine: current and future impact.
AB  - Diseases caused by Streptococcus pneumoniae contribute significantly to worldwide
      morbidity and mortality. S. pneumoniae is now the number one cause of invasive
      bacterial disease in children in countries where Haemophilus influenzae type b
      (Hib) disease has been conquered by use of the Hib conjugate vaccine. Licensure
      of a heptavalent pneumococcal conjugate vaccine for prevention of invasive
      pneumococcal disease in children less than 5 years old in the USA represents the
      culmination of more than five decades of pneumococcal vaccine development. This
      review will: highlight safety, immunogenicity and efficacy studies that led to US
      Food and Drug Administration approval of this PCV7; summarize data about the
      incidence of childhood pneumococcal disease in the USA subsequent to licensure;
      review PCV7 treatment guidelines currently in place in the USA, Canada and
      Australia; and consider future directions in pneumococcal vaccine research.

PMID- 14711325
TI  - Conjugate vaccines.
AB  - Conjugate vaccines in which the capsular polysaccharide of Haemophilus influenzae
      type b, common serotypes of Streptococcus pneumoniae and group C Neisseria
      meningitidis are covalently bound to a protein antigen to convert a T-cell
      independent immune response into a T-cell-dependent response have proved highly
      effective in the prevention of invasive disease in infants and young children.
      This review looks at what has been learnt from developing these vaccines that
      could be useful for the clinical development of future conjugate vaccines, in
      such areas as combination vaccines, dose-ranging, cross-protection of closely
      related antigens, prevention of noninvasive disease, correlates of protection and
      use in older age groups. In addition, a wide range of other organisms may be
      susceptible to conjugate vaccines and new indications and approaches are
      considered. This will be a highly active area for many years to come.

PMID- 14711326
TI  - Methodological issues and new developments in the economic evaluation of
      vaccines.
AB  - The application of economic evaluation in healthcare, including vaccination
      programs, has increased exponentially since the 1980s. There are a number of
      aspects of economic evaluation of vaccine programs that present particular
      challenges to the analyst. These include the development of the appropriate
      epidemiological models from which to estimate the costs and benefits; the
      accurate prediction of uptake rates; the incorporation of quality adjusted
      survival gains; and the inclusion of intangible but nonetheless important
      benefits and costs associated with infectious disease and vaccination. The
      estimation of marginal intervention costs presents specific difficulties,
      especially for multivalent vaccines and valuing costs and benefits over time is
      heavily influenced by the choice of discount rate, which is still a controversial
      topic. Developments in the next 5 years are likely to address all of these issues
      and result in more sophisticated and accurate models of vaccination programs.

PMID- 14711327
TI  - Hepatitis A and considerations regarding the cost-effectiveness of vaccination
      programs.
AB  - Hepatitis A vaccines have demonstrated a high degree of immunogenicity and an
      excellent safety profile. Immunization of certain populations and patient
      subgroups is recommended according to specific epidemiological and clinical
      factors, such as a greater likelihood of acquisition of infection or concerns
      regarding the risk of development of fulminant hepatitis and death. Therefore,
      the economic implications of routine and/or targeted vaccination programs in the
      general population and high-risk individuals have been examined. In this
      manuscript, the available data from the literature regarding the cost
      effectiveness of hepatitis vaccination programs in healthy individuals and in
      those with chronic liver disease are reviewed.

PMID- 14711328
TI  - Meningococcal serogroup B infections: a search for a broadly protective vaccine.
AB  - Meningococcal disease is mainly caused by serogroup B in many West European
      countries. Recently, a highly efficacious vaccine against infections caused by
      serogroup C has been introduced in the UK and The Netherlands. However, an
      effective vaccine against serogroup B has not yet become available. Outer
      membrane vesicle vaccines against serogroup B were previously tested in large
      Phase III trials but showed a low efficacy in young children. In addition, the
      high variability of the vaccines' main component, porin A, potentially diminishes
      its efficacy. Therefore, several approaches in either optimizing these outer
      membrane vesicle vaccines or searching for novel, highly conserved antigens are
      currently under investigation. The sequencing of the meningococcal genome has
      provided new opportunities to detect additional immunogenic epitopes. In this
      review, the developments in the search for a broadly protective meningococcal
      serogroup B vaccine will be discussed.

PMID- 14711329
TI  - Progress and controversy surrounding vaccines against Lyme disease.
AB  - Less than 20 years elapsed between the 1982 report of the identification and
      isolation of Borrelia burgdorferi and the licensure and marketing in the USA of a
      prophylactic vaccine against this pathogen. However, the manufacturer removed the
      vaccine from the market under 4 years after its release. The low demand
      undoubtedly was the result of limited efficacy, need for frequent boosters, the
      high price of the vaccine, exclusion of children, fear of vaccine-induced
      musculoskeletal symptoms and litigation surrounding the vaccine. Second
      generation polyvalent outer surface protein (Osp)C vaccines may overcome some of
      these concerns but the precise antigenic components required for efficacy are
      uncertain. The development of the next generation of Lyme disease vaccines is in
      its infancy.

PMID- 14711330
TI  - Vaccines in leishmaniasis: advances in the last five years.
AB  - The leishmaniases are a group of diseases caused by protozoa of the genus
      Leishmania which affects millions of people worldwide. The leishmaniases are
      transmitted to the vertebrate hosts by phlebotomine sand flies. In this review,
      we focus on clinical aspects of the leishmaniases and on the immune response
      against the parasite, both in animal models and humans. These aspects are of key
      importance to understand the many attempts to obtain an effective vaccine against
      Leishmania. We considered the last advances in new generation vaccines, including
      the use of new adjuvants to improve the protective response against the parasite.
      Finally, the possibility to use components of the sand fly saliva as part of
      vaccines against the infection by Leishmania is mentioned.

PMID- 14711331
TI  - Development of a SARS vaccine: an industrial perspective on the global race
      against a global disease.

PMID- 14711332
TI  - HIV adenovirus vaccine in Phase I trials.

PMID- 14711333
TI  - Pharmacoeconomics of elderly vaccination against invasive pneumococcal
      infections: cost-effectiveness analyses and implications for The Netherlands.
AB  - We performed a review of cost-effectiveness of elderly pneumococcal vaccination
      to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands
      and Spain and a multinational study of five European countries. Cost
      effectiveness of elderly vaccination against invasive pneumococcal infections
      varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study
      estimates cost-effectiveness at EUR 10,100 per life-year gained (price level:
      1995). This is below the level that has recently been defined for treatment of
      high cholesterol (EUR 20,000 per life-year gained) and may therefore be
      considered as favorable. Almost all studies base their estimate of vaccine
      efficacy on the same case-control study from the USA. We identify a need for a
      systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest
      further analysis with respect to potential effects on cost-effectiveness of
      extended influenza vaccination for the Dutch elderly in recent years and
      inclusion of pneumococcal re-vaccination. Pending this additional information, we
      conclude that cost-effectiveness of vaccination against invasive pneumococcal
      infections for Dutch elderly is favorable (as in several other countries) and
      justifies implementation from a pharmacoeconomic point of view.

PMID- 14711334
TI  - Strategies for the development of PSA-based vaccines for the treatment of
      advanced prostate cancer.
AB  - Prostate cancer is the second leading cause of cancer death in males in the USA.
      Vaccine strategies represent a novel therapeutic approach. One potential target
      for a prostate cancer vaccine is prostate-specific antigen (PSA), due to its
      restricted expression in prostate cancer and normal prostatic epithelial cells. A
      number of PSAspecific epitopes have been identified that can activate cytotoxic T
      lymphocytes (CTLs) and in turn lead to the killing of tumor targets by the
      peptide-specific CTLs. Strategies have now been employed in clinical trials using
      RNA-pulsed dendritic cell vaccines, recombinant protein vaccines, and recombinant
      viral vector delivery of vaccines. Newer approaches incorporating costimulatory
      molecules that enhance Tcell activation are also being investigated.

PMID- 14711335
TI  - Preventative and therapeutic vaccines for cervical cancer.
AB  - "High-risk" genotypes of the human papillomavirus (HPV), most commonly HPV
      genotype 16, are the primary etiologic agents of cervical cancer. Indeed HPV DNA
      is detected in 99% of cervical carcinomas. Thus, cervical cancer and other HPV
      associated malignancies might be prevented or treated by the induction of the
      appropriate viral-antigen-specific immune responses. Transmission of
      papillomavirus may be prevented by the generation of antibodies to capsid
      proteins L1 and L2 that neutralize viral infection. HPV L1 virus-like particles
      (VLPs) show great promise as prophylactic HPV vaccines in ongoing clinical trials
      but L2-based preventative vaccines have yet to be tested in patients. Since the
      capsid proteins are not expressed at detectable levels by infected basal
      keratinocytes or in HPV-transformed cells, therapeutic vaccines generally target
      the nonstructural early viral antigens. Two HPV oncogenic proteins, E6 and E7,
      are critical to the induction and maintenance of cellular transformation and are
      co-expressed in the majority of HPV-containing carcinomas. Although other early
      viral antigens show promise for vaccination against papillomas, therapeutic
      vaccines targeting E6 and E7 may provide the best opportunity to control HPV
      associated malignancies. Various candidate therapeutic HPV vaccines are currently
      being tested whereby E6 and/or E7 are administered in live vectors, as peptides
      or proteins, in nucleic acid form, as components of chimeric VLPs, or in cell
      based vaccines. Encouraging results from experimental vaccination systems in
      animal models have led to several prophylactic and therapeutic vaccine clinical
      trials. Should this new generation of HPV preventative and therapeutic vaccines
      function in patients as demonstrated in animal models, oncogenic HPV infection
      and its associated malignancies could be controlled by vaccination. Importantly,
      recent advances in HPV detection and continued improvements in screening further
      enhance our opportunities to systematically eradicate HPV-associated malignancy.

PMID- 14711336
TI  - Novel approaches to therapeutic cancer vaccines.
AB  - Although tumor vaccines have been studied for decades, there is no vaccine
      approved as a clinical product. Nevertheless, recent advances in immunology and
      tumor biology justify a renewed interest. First, cancer cells express many
      antigens that can be recognized by the immune system, some with high tumor
      selectivity. Second, knowledge about immune regulation, including the importance
      of costimulatory signals, has been successfully applied to the studies of tumors.
      Third, mechanisms of how tumors can escape from immunological control have been
      identified, setting the stage to discover agents to decrease their impact.
      Rejection of established mouse tumors has been accomplished as a result of
      therapeutic tumor vaccination and there are encouraging findings from vaccine
      trials in humans.

PMID- 14711337
TI  - Prevention of autoimmune diabetes by DNA vaccination.
AB  - DNA vaccination with antigen expression plasmids has been introduced as a simple
      method of inducing immunity to the antigens of infectious agents or tumors.
      Although DNA vaccination is generally immunostimulatory, it is possible to design
      suppressive vaccines that protect against autoimmune diseases such as Type 1
      diabetes. In mice prone to diabetes, investigators have delivered a plasmid
      encoding an islet-cell antigen such as insulin B chain, glutamic acid
      decarboxylase, or antigen/immunoglobulin G-Fc fusion constructs, with or without
      co-delivery of another gene encoding a cytokine or other immunoregulatory
      molecule. This approach has led to protection against disease, related to the
      generation of regulatory T-cells and increased production of regulatory
      cytokines. DNA vaccination is a promising approach to autoimmune disease
      prevention.

PMID- 14711338
TI  - Development of prophylactic vaccines for genital and neonatal herpes.
AB  - Over five decades numerous conventional candidate live attenuated and killed
      vaccines have failed to prevent genital herpes in clinical trials. However, a
      vaccine consisting of recombinant glycoprotein D from herpes simplex virus (HSV)
      2 and deacylated monophosphoryl lipid A adjuvant has recently shown partial
      efficacy against clinical disease transmitted from HSV-1 and -2 seronegative
      women (73-74%). Comparisons between the efficacy of this vaccine and previous
      failed candidates and their effects on the immune system should help guide
      development of better vaccines through selection of appropriate HSV proteins,
      adjuvants or cytokines and newer vaccine vectors, such as DNA vaccines,
      recombinant viral vaccines and specific HSV mutants.

PMID- 14711339
TI  - Mucosal immunization against respiratory bacterial pathogens.
AB  - Bacterial respiratory diseases remain a major cause of morbidity and mortality
      throughout the world. The young and the elderly are particularly susceptible to
      the pathogens that cause these diseases. Therapeutic approaches remain dependent
      upon antibiotics contributing to the persistent increases in antibiotic
      resistance. The main causes of respiratory disease discussed in this review are
      Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordatella pertussis,
      Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella
      catarrhalis and Pseudomonas aeruginosa. All these organisms initiate disease at
      the mucosal surface of the respiratory tract and thus the efficacy of the host's
      response to infection needs to be optimal at this site. Vaccines available for
      diseases caused by many of these pathogens have limitations in accessibility or
      efficacy, highlighting the need for improvements in approaches and products. The
      most significant challenges in both therapy and prevention of disease induced by
      bacteria in the respiratory tract remain the development of non-injectable
      vaccines and delivery systems/immunization regimens that improve mucosal
      immunity.

PMID- 14711340
TI  - Prospects for vaccine development against Buruli disease.
AB  - Buruli disease, caused by Mycobacterium ulcerans, is an emerging infectious
      disease in tropical areas, particularly West Africa, which can cause deep
      necrotizing skin lesions, called Buruli ulcer. Buruli disease affects all age
      groups but about 50% of the cases are diagnosed in children. There is no evidence
      that Buruli disease is transmitted by direct person-to-person contact and it is
      very likely that contaminated water of rivers, swamps and lakes serves as the
      wildlife reservoir of M. ulcerans. This review briefly discusses the
      epidemiology, microbiology, pathology and treatment of the disease. It describes
      in detail the current knowledge of the immune response and focuses on the studies
      that have dealt with vaccination. Finally, experimental approaches for future
      immunoprophylaxis are discussed.

PMID- 14711341
TI  - Neisseria meningitidis serogroup A vaccines: an overview.
AB  - A recent report by the Weekly Epidemiological Record of an outbreak of Neisseria
      meningitidis serogroup A in the Great Lakes region shows that meningococcal
      epidemics are an unsolved problem in resource-poor countries, particularly in
      Africa [1]. During the last epidemic wave in the 1990s, about 350,000 people
      developed meningitis and 1000 people died [101]. An effective polysaccharide
      vaccine has been available since the early 1970s. Unfortunately, attempts to
      contain the epidemics by timely detection of cases through active surveillance
      and prompt mass vaccination campaigns have failed to prevent the deaths of
      thousands of people in several African countries in the 1980s and 1990s. This
      article describes the epidemiology of N. meningitidis serogroup A, the available
      polysaccharide vaccines, their advantages and limitations. The current
      vaccination policies and their economic implications are discussed, to clarify
      why the use of an effective vaccine has, to date, been disappointing. The recent
      exciting developments with respect to conjugate vaccines are described.

PMID- 14711342
TI  - Advances in the identification and characterization of protective antigens for
      recombinant vaccines against tick infestations.
AB  - Ticks are economically important ectoparasites of domestic and wild animals and
      are considered to be second worldwide to mosquitoes as vectors of human
      pathogens. Current control methods for ticks, based primarily on the use of
      acaricides, have had limited efficacy in the reduction of tick infestations and
      the use of acaricides is often accompanied by serious drawbacks, including
      selection of acaricide-resistant ticks and environmental contamination.
      Development of improved vaccines against tick infestations offers a cost
      effective and environmentally sound control method. Commercial vaccines currently
      marketed for control of cattle ticks have been effective in field studies when
      used in concert with integrated control strategies. However, new antigens are
      needed to increase the efficacy of tick vaccines. Although a limited number of
      protective antigens against tick infestations have been identified and
      characterized, discovery of new antigens remains the limiting step for improving
      the efficacy of tick vaccines. Recent technologies developed for gene discovery,
      including expression library immunization and evaluation of expressed sequence
      tags, show promise for rapid, systematic and global antigen screening and should
      provide a comprehensive approach to selection of candidate vaccine antigens.
      Design of future tick vaccines should target multiple tick species, as well as
      interfere with the transmission of pathogens.

PMID- 14711343
TI  - From bioarrays to diagnostics: a systemomics approach.

PMID- 14711345
TI  - Expediting target identification and validation through RNAi.

PMID- 14711346
TI  - Spinal muscular atrophy: molecular genetics and diagnostics.
AB  - Spinal muscular atrophy is one of the most common autosomal recessive diseases,
      affecting approximately one in 10,000 live births and with a carrier frequency of
      approximately one in 50. Spinal muscular atrophy is caused by a deficiency of the
      ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN
      genes, SMN1 and SMN2. Due to a single nucleotide polymorphism (840C>T), SMN2
      produces less full-length transcript than SMN1 and cannot entirely prevent
      neuronal cell death at physiologic gene dosages. The 38-kDa SMN protein comprises
      294 amino acids and is involved in the biogenesis of uridine-rich small nuclear
      ribonucleoproteins, facilitating their cytoplasmic assembly into the spliceosome.
      Various animal models have been developed to study the pathogenesis of spinal
      muscular atrophy, as well as to test novel therapeutics. Common PCR-restriction
      fragment length polymorphism assays can detect the homozygous absence of SMN1 in
      approximately 94% of patients with clinically typical spinal muscular atrophy.
      SMN gene dosage analysis can determine the copy number of SMN1 to detect carriers
      and patients heterozygous for the absence of SMN1. Due to the genetic complexity
      and the high carrier frequency, accurate risk assessment and genetic counseling
      are particularly important. Comprehensive SMA genetic testing, combined with
      appropriate genetic counseling and risk assessment, provides the most complete
      evaluation of patients and their families at this time. New technologies, such as
      monosomal analysis techniques, may be widely available in the future.

PMID- 14711347
TI  - Recent advances in forensic genetics.
AB  - Like many applications of molecular diagnostics, the field of forensic biology is
      undergoing a phase of expansion and diversification. The growth of forensic DNA
      databases and adoption of sophisticated analytical methods have catalyzed this
      increasing role. The range of molecular markers exploited in the fight against
      crime is beginning to increase too, and genes implying personal or physical
      characteristics are emerging in the research literature. However, the operational
      context of forensic biology is unlike many other fields of science. Harmonizing
      technological breakthroughs with the requirements of law enforcement agencies and
      the complexities of the legal system is an added challenge and one which evokes
      ongoing debate. This review examines the current status of this dynamic and
      important application of modern genetics.

PMID- 14711348
TI  - Principle and applications of digital PCR.
AB  - Digital PCR represents an example of the power of PCR and provides unprecedented
      opportunities for molecular genetic analysis in cancer. The technique is to
      amplify a single DNA template from minimally diluted samples, therefore
      generating amplicons that are exclusively derived from one template and can be
      detected with different fluorophores or sequencing to discriminate different
      alleles (e.g., wild type vs. mutant or paternal vs. maternal alleles). Thus,
      digital PCR transforms the exponential, analog signals obtained from conventional
      PCR to linear, digital signals, allowing statistical analysis of the PCR product.
      Digital PCR has been applied in quantification of mutant alleles and detection of
      allelic imbalance in clinical specimens, providing a promising molecular
      diagnostic tool for cancer detection. The scope of this article is to review the
      principles of digital PCR and its practical applications in cancer research and
      in the molecular diagnosis of cancer.

PMID- 14711349
TI  - Prenatal screening for cystic fibrosis: past, present and future.
AB  - Prenatal screening for cystic fibrosis is reviewed. The disease, gene involved,
      molecular basis of disease, genotype/phenotype correlations and pilot trials are
      discussed, as well as historical perspectives, background and American College of
      Medical Genetics/American College of Obstetricians and Gynecologists
      recommendations. A number of complex challenges to the implementation of cystic
      fibrosis screening exist, including mutation testing of the cystic fibrosis
      transmembrane conductance regulator gene (CFTR), as well as laboratory and
      clinical issues. Current technologies for CFTR testing include reverse dot blots,
      amplification refractory mutation detection systems, oligonucleotide ligation
      assays, the Invader assay and NanoChip system. Emerging technologies are also
      considered, as well as quality assurance measures including analytical and
      clinical validation, reporting, residual risk calculations and prenatal
      diagnosis. An even greater challenge is clinical implementation, which focuses
      upon education and communication, choosing models, reporting, counseling and
      prenatal diagnosis.

PMID- 14711350
TI  - Accuracy of early diagnosis and its impact on the management and course of
      Alzheimer's disease.
AB  - Alzheimer's disease is the most common form of dementia in the elderly and its
      prevalence is rapidly rising. Although there is no cure for Alzheimer's disease,
      treatment can be administered to slow progression or delay the onset of symptoms.
      A major challenge is the early identification of patients who will develop
      Alzheimer's disease. As disease-modifying treatments become available, enhancing
      our ability to identify Alzheimer's early and accurately would allow intervention
      to slow, halt or even prevent disease progression or onset. Early recognition and
      intervention facilitates optimal care of Alzheimer's patients and delays the
      morbidity associated with this progressive illness.

PMID- 14711351
TI  - Clinical implications of advanced molecular cytogenetics in cancer.
AB  - The field of cytogenetics has already entered the molecular era and a rapid
      expansion of its contribution is seen in genomic disease management. Among the
      evolving advanced molecular techniques, with an impeccable balance of high
      specificity, sensitivity and assay rapidity, fluorescence in situ hybridization
      has made its home in routine clinical laboratory. Today, its clinical application
      is vivid in every phase of disease management of a number of malignancies. The
      rapid growth in the knowledge of specific associations between distinct
      chromosomal abnormalities and different types of cancers will necessitate
      simultaneous detection of multiple abnormalities using multicolor/multiplex
      fluorescence in situ hybridization tests more often in the near future. Also, as
      the human genome sequence is ascertained, genome-wide screening with microarray
      technology will gain eminence in the clinical scenario, yield better solutions
      and bring the concept of personalized medicine in cancer closer to reality than
      ever before.

PMID- 14711352
TI  - Role of molecular studies in the classification of lymphoma.
AB  - The classification of lymphomas has historically lacked both precision and
      accuracy, potentially compromising both optimal diagnosis and therapy. The
      genetic characterization of key oncogenic events and the advent of expression
      profiling have afforded the opportunity to understand, diagnose and treat these
      diseases in a much more rational and targeted manner. As exciting as these new
      and testable data are, it is also worth noting that molecular genetic analysis of
      the tumor in isolation will not be the sole arbiter of patient outcome. It is
      likely that we will remain reliant on traditional and sometimes subjective
      technologies, albeit probably to a lesser degree, with molecular studies
      significantly complementing, but certainly not replacing, microscopic,
      immunophenotypic and cytogenetic approaches. Furthermore, we will perhaps need to
      extend genotyping to the tumor milieu (the patient) in order to molecularly
      dissect drug metabolic pathways and the immune response.

PMID- 14711353
TI  - Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and
      molecular genetic testing.
AB  - Hypertrophic cardiomyopathy is a Mendelian disease characterized by cardiac
      hypertrophy. It has a prevalence of 1:500 individuals and is the most common
      cause of sudden death in the young. Other complications include heart failure and
      the need for heart transplantation. Hypertrophic cardiomyopathy is due to
      sarcomeric gene mutations, however, phenocopies with myocardial hypertrophy can
      be due to triplet-repeat syndromes (Friedreich ataxia and myotonic dystrophy),
      mitochondrial and metabolic diseases. In a peculiar form associated with Wolf
      Parkinson-White syndrome, the disease is caused by mutations in the gamma2
      regulatory subunit of the AMP-activated protein kinase gene, leading to a
      glycogen storage cardiomyopathy. In spite of the growing knowledge about the
      molecular basis of hypertrophic cardiomyopathy, very little is still known about
      the genotype-phenotype correlations and their clinical implications. In this
      review, the clinical and molecular genetics of hypertrophic cardiomyopathy are
      described.

PMID- 14711354
TI  - Diagnosis of human brucellosis using PCR.
AB  - Brucellosis is a zoonosis caused by facultative intracellular bacteria of the
      genus Brucella, which are widely distributed in both humans and animals,
      especially in the developing world. The diagnosis of human brucellosis requires
      isolation of the bacteria or confirmation through serologic tests. However,
      culture sampling sensitivity is often low, depending on the disease stage,
      Brucella species, culture medium, quantity of circulating bacteria and blood
      culture technique employed. The development of the PCR has offered a new
      dimension in the diagnosis of different microorganisms, which is possible in just
      a few hours. Over the past decade, there have been major advancements in all
      aspects of molecular diagnostics with regard to human brucellosis. PCR-based
      tests are proving to be faster and more sensitive than traditional methods.
      However, the sensitivity and specificity of the PCR for Brucella vary between
      laboratories and no standardization of sample preparation, target genes and
      detection methods have been established yet. Therefore, in this study, all the
      important aspects of the PCR for Brucella DNA detection and its utility in the
      diagnosis and follow-up of patients with brucellosis are reviewed.

PMID- 14711355
TI  - Vaccine safety: a case for synthetic vaccine formulations.

PMID- 14711356
TI  - AIDSVAX fails to prove efficacious in large-scale trial.

PMID- 14711357
TI  - Francisella: a little bug hits the big time.

PMID- 14711358
TI  - The potential role of the HIV-1 immunogen (Remune) as a therapeutic vaccine in
      the treatment of HIV infection.
AB  - Immune-based therapies, such as therapeutic vaccination, that might preserve,
      restore, enhance and induce new HIV-specific immunologic responses are currently
      being explored. HIV-specific immunotherapy with Remune (The Immune Response
      Corp.) offers the opportunity to boost immune responses against HIV-1. The
      clinical trial program in a wide range of subjects has established the efficacy
      of Remune in stimulating an appropriate immune response in HIV-positive
      individuals. Furthermore, a recent unblinded study conducted in Europe has
      documented a significant effect of Remune on viral load. Evidence regarding
      clinical end points is more difficult to collect. The same studies have revealed
      no serious safety issues in a total of more than 2000 Remune-treated patients. It
      is therefore reasonable to suggest that the risk-benefit ratio of Remune could be
      positive.

PMID- 14711359
TI  - Delivering vaccines into the skin without needles and syringes.
AB  - The skin is a highly accessible organ and due to the presence of powerful antigen
      presenting cells in the epidermis, it functions as an immune barrier. This makes
      the skin an attractive route for potential delivery of vaccines by painless and
      user-friendly methods without the requirement of needles and syringes. This
      article reviews current attempts to administer vaccines into the skin and
      discusses some of the scientific issues related to the emerging delivery
      technologies.

PMID- 14711360
TI  - Plant production systems for vaccines.
AB  - Plants offer an attractive alternative for the production and delivery of subunit
      vaccines. Various antigens have been expressed at sufficiently high levels in
      plants to render vaccine development practical. An increasing body of evidence
      demonstrates that these plant-produced antigens can induce immunogenic responses
      and confer protection when delivered orally. Plant-based vaccines are relatively
      inexpensive to produce and production can be rapidly scaled up. There is also the
      potential for oral delivery of these vaccines, which can dramatically reduce
      distribution and delivery costs. Here we describe the technology to develop plant
      based vaccines, review their advantages and discuss potential roadblocks and
      concerns over their commercialization. We also speculate on likely future
      developments with these vaccines and on their potential impact in the realms of
      human and animal health.

PMID- 14711361
TI  - Towards a vaccine against Ebola virus.
AB  - Ebola virus infection causes hemorrhagic fever with high mortality rates in
      humans and nonhuman primates. Currently, there are no vaccines or therapies
      approved for human use. Outbreaks of Ebola virus have been infrequent, largely
      confined to remote locations in Africa and quarantine of sick patients has been
      effective in controlling epidemics. In the past, this small global market has
      generated little commercial interest for developing an Ebola virus vaccine.
      However, heightened awareness of bioterrorism advanced by the events surrounding
      September 11, 2001, concomitant with knowledge that the former Soviet Union was
      evaluating Ebola virus as a weapon, has dramatically changed perspectives
      regarding the need for a vaccine against Ebola virus. This review takes a brief
      historic look at attempts to develop an efficacious vaccine, provides an overview
      of current vaccine candidates and highlights strategies that have the greatest
      potential for commercial development.

PMID- 14711362
TI  - Under-explored experimental topics related to integral mycobacterial vaccines for
      leprosy.
AB  - Many leprosy vaccine studies have utilized live or killed whole mycobacteria,
      such as Bacille Calmette-Guerin, Indian Cancer Research Center (ICRC) bacilli and
      Mycobacterium w either alone or in combination with killed Mycobacterium leprae.
      For Bacille Calmette-Guerin, the vaccine dose is generally that which gives the
      largest delayed-type hypersensitivity response with minimal side effects. The
      doses of other integral mycobacterial vaccines appear to be arbitrarily chosen.
      Hypotheses governing immunologic responses to complex antigens predict that the
      doses used may be too high, resulting in protection of some individuals and
      increasing the susceptibility of other individuals to leprosy. The natural
      history of an individual's prior exposure to environmental mycobacteria will
      affect the outcome of protective vaccination using a given dose of mycobacterial
      vaccine in the individual.

PMID- 14711363
TI  - Vaccination procedures against Coxsackievirus-induced heart disease.
AB  - Coxsackievirus B3--a member of the picornavirus family--is one of the major
      causes of virus-induced acute or chronic heart disease. Despite the fact that the
      molecular structure of this pathogen has been characterized very precisely during
      the last 10 years, until recently, there was no virus-specific preventive or
      therapeutic procedure against Coxsackievirus B3-induced human heart disease in
      clinical use. However, using different murine model systems it has been
      demonstrated that classic as well as newly developed vaccination procedures are
      quite successful in preventing Coxsackievirus B3 infections. In particular, the
      application of an interferon-gamma-expressing recombinant Coxsackievirus variant
      against Coxsackievirus B3-induced myocarditis has been effective.

PMID- 14711364
TI  - Ganglioside-based vaccines and anti-idiotype antibodies for active immunotherapy
      against cancer.
AB  - This review shall present an update in anticancer ganglioside-based
      immunotherapies, with particular emphasis on molecular vaccines and anti-idiotype
      mAbs produced by the Center of Molecular Immunology (Havana, Cuba). The project
      comprises vaccines of N-acetyl or N-glycolylneuraminic acid GM3 ganglioside
      incorporated into very small proteoliposomes and anti-idiotype antibodies to
      glycolylated gangliosides. Development of these vaccine preparations from
      preclinical models of melanoma, breast and lung cancer to human investigation is
      summarized. A brief discussion on the progress and limitations of present-day
      clinical trials and future prospects is also included.

PMID- 14711365
TI  - Dendritic cell vaccination and immunostimulation in advanced melanoma.
AB  - The most recent advances in immunology bear witness to the fact that tumors, in
      particular melanoma, escape recognition by the host's immune system and can
      locally inactivate its effectors, T-cells and antigen presenting cells. There is,
      however, preclinical evidence that the immune system, opportunely stimulated, is
      capable of recognizing and killing tumor cells. It has been verified that the
      activation of autologous dendritic cells, derived from peripheral blood and
      pulsed with tumor antigens, results in the specific stimulation of T-cells
      against the tumor. Preliminary data from dendritic cell vaccination trials,
      mainly of advanced melanoma, show unequivocal evidence of immunization and of the
      first clinical responses. Many questions remain to be answered before more
      effective and widespread use of this type of vaccination is possible, especially
      in the early stages of the disease.

PMID- 14711366
TI  - 17beta-Oestradiol enhances aortic endothelium function and smooth muscle
      contraction in male spontaneously hypertensive rats.
AB  - 17beta-Oestradiol (E(2); oestrogen) is known to increase endothelium-dependent
      vasodilatation and NO (nitric oxide) production. It is also known to decrease the
      response of VSMCs (vascular smooth muscle cells) to vasoconstrictors in vitro.
      E(2) induces a decrease in age-related BP (blood pressure) development in MSHR
      (male spontaneously hypertensive rats). Whether this decrease is due to an effect
      on the endothelium or smooth muscle is unknown. To determine this effect, we
      examined the role of E(2) on vascular endothelium and smooth muscle separately.
      We treated MSHR with E(2) (2 mg x kg(-1) of body weight x week(-1)) for 5-7 weeks
      and then examined the vasoconstrictor response in the intact and denuded rings
      (with or without endothelium respectively). SBP (systolic BP) was measured
      weekly. Aortic cGMP and cAMP contents, aortic vasoconstrictor response,
      endothelium suppression of the vasoconstrictor response and basal NO release from
      aortic rings were all measured at the end of the study. We found that the age
      related development of SBP in MSHR was decreased in E(2)-treated rats. The
      vascular response of denuded rings to a vasoconstrictor (phenylephrine and KCl)
      was increased in E(2)-treated rats; however, this phenomenon was masked in intact
      rings. The enhanced endothelial function appears to override the E(2)-increased
      smooth muscle vasoconstrictor response. Endothelium suppression, NO release and
      aortic cGMP content were all significantly higher in E(2)-treated rats than in
      controls. Thus our results suggest that E(2) improves endothelium function;
      furthermore, the accompanied NO/cGMP increase and the endothelium suppression may
      be associated with an E(2)-induced BP-lowering effect in MSHR.

PMID- 14711367
TI  - Variability of inspiratory conductance quantifies flow limitation.
AB  - In the present study, our aim was to investigate whether the variability of
      conductance over the course of inspiration reflects flow limitation.
      Pressure/flow conditions in the upper airway were modelled by a collapsible tube
      within a rigid chamber and a pump simulating respiration. Instantaneous
      conductance was estimated every 20 ms as flow/resistive pressure, and its
      variability during inspiration expressed as the 90th/50th percentile ratio.
      Accuracy of this ratio to quantify flow limitation was evaluated by observing
      whether it changed predictably with adjustments of model parameters. To
      illustrate the potential of this ratio to quantify flow limitation in a clinical
      setting, we recorded pneumotachographic airflow and oesophageal pressure in 11
      patients with obstructive sleep apnoea during nasal continuous positive airway
      pressure (CPAP) ventilation, and observed changes in the 90th/50th percentile
      ratio of inspiratory lung conductance induced by mask pressure titration. Rising
      pressure surrounding the collapsible tube from subatmospheric to positive values
      induced progressive inspiratory collapse and increased 90th/50th percentile
      ratios of inspiratory conductance as predicted. Changes in flow limitation
      induced by other model modifications were also correctly tracked by the 90th/50th
      conductance percentile ratio. Increasing mask pressure during CPAP ventilation in
      sleep apnoea patients from subtherapeutic to therapeutic pressure levels was
      associated with the expected decrease in the 90th/50th percentile ratio of
      inspiratory lung conductance from a mean of 6.5+/-3.1 to 1.6+/-0.3 ( P <0.001).
      We conclude that variability of inspiratory conductance quantified by the
      90th/50th percentile ratio may serve as a measure of flow limitation that is
      independent of the absolute value of conductance.

PMID- 14711368
TI  - The tumour-suppressor function of PTEN requires an N-terminal lipid-binding
      motif.
AB  - The PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumour
      suppressor protein is a phosphoinositide 3-phosphatase which antagonizes
      phosphoinositide 3-kinase-dependent signalling by dephosphorylating
      PtdIns(3,4,5)P3. Most tumour-derived point mutations of PTEN induce a loss of
      function, which correlates with profoundly reduced catalytic activity. However,
      here we characterize a point mutation at the N-terminus of PTEN, K13E from a
      human glioblastoma, which displayed wild-type activity when assayed in vitro.
      This mutation occurs within a conserved polybasic motif, a putative PtdIns(4,5)P2
      binding site that may participate in membrane targeting of PTEN. We found that
      catalytic activity against lipid substrates and vesicle binding of wild-type
      PTEN, but not of PTEN K13E, were greatly stimulated by anionic lipids, especially
      PtdIns(4,5)P2. The K13E mutation also greatly reduces the efficiency with which
      anionic lipids inhibit PTEN activity against soluble substrates, supporting the
      hypothesis that non-catalytic membrane binding orientates the active site to
      favour lipid substrates. Significantly, in contrast to the wild-type enzyme, PTEN
      K13E failed either to prevent protein kinase B/Akt phosphorylation, or inhibit
      cell proliferation when expressed in PTEN-null U87MG cells. The cellular
      functioning of K13E PTEN was recovered by targeting to the plasma membrane
      through inclusion of a myristoylation site. Our results establish a requirement
      for the conserved N-terminal motif of PTEN for correct membrane orientation,
      cellular activity and tumour-suppressor function.

PMID- 14711369
TI  - A novel copper site in a cyanobacterial metallochaperone.
AB  - The thylakoid lumen of the cyanobacterium Synechocystis PCC 6803 is supplied with
      copper via two copper-transporting ATPases and a metallochaperone intermediary.
      We show that the copper site of this metallochaperone is unusual and consists of
      two cysteine residues and a histidine imidazole located on structurally dynamic
      loops. Substitution of this histidine residue enhances bacterial two-hybrid
      interaction with the cytosolic copper exporter, but not the copper importer,
      suggesting that the interacting surfaces are distinct, with implications for
      metal transfer.

PMID- 14711370
TI  - Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like
      activity: physiological significance and caveats of in vitro aggregation assays.
AB  - Alpha-crystallin is a member of the small heat-shock protein family and functions
      like a molecular chaperone, and may thus help in maintaining the transparency of
      the eye lens by protecting the lens proteins from various stress conditions. Non
      enzymic glycation of long-lived proteins has been implicated in several age- and
      diabetes-related complications, including cataract. Dicarbonyl compounds such as
      methylglyoxal and glyoxal have been identified as the predominant source for the
      formation of advanced glycation end-products in various tissues including the
      lens. We have investigated the effect of non-enzymic browning of alpha-crystallin
      by reactive dicarbonyls on its molecular chaperone-like function. Non-enzymic
      browning of bovine alpha-crystallin in vitro caused, along with altered secondary
      and tertiary structures, cross-linking and high-molecular-mass aggregation.
      Notwithstanding these structural changes, methylglyoxal- and glyoxal-modified
      alpha-crystallin showed enhanced anti-aggregation activity in various in vitro
      aggregation assays. Paradoxically, increased chaperone-like activity of modified
      alpha-crystallin was not associated with increased surface hydrophobicity and
      rather showed less 8-anilinonaphthalene-l-sulphonic acid binding. In contrast,
      the chaperone-like function of modified alpha-crystallin was found to be reduced
      in assays that monitor the prevention of enzyme inactivation by UV-B and heat.
      Moreover, incubation of bovine lens with methylglyoxal in organ culture resulted
      in cataract formation with accumulation of advanced glycation end-products and
      recovery of alpha-crystallin in high proportions in the insoluble fraction.
      Furthermore, soluble alpha-crystallin from methylglyoxal-treated lenses showed
      decreased chaperone-like activity. Thus, in addition to describing the effects of
      methylglyoxal and glyoxal on structure and chaperone-like activity, our studies
      also bring out an important caveat of aggregation assays in the context of the
      chaperone function of alpha-crystallin.

PMID- 14711371
TI  - The lipid composition of high-density lipoprotein affects its re-absorption in
      the kidney by proximal tubule epithelial cells.
AB  - The kidney is believed to play a major role in the clearance of apoA-I
      (apolipoprotein A-I) and HDL (high-density lipoprotein) particles from the
      bloodstream. Proximal tubule epithelial cells of the kidney appear to prevent the
      loss of these proteins in the urine by re-absorbing them from the urinary
      filtrate. Experiments were undertaken to investigate the factors that regulate
      the renal re-absorption of apoA-I and small HDL in a transformed human proximal
      tubule epithelial (HKC-8) cell line. Fluorescent microscopic studies show that
      HKC-8 cells can readily bind and take up HDL particles. Intracellular
      localization of fluorescently labelled native HDL shows its accumulation in
      endocytotic vesicles, in a perinuclear region after 1 h. Binding studies reveal a
      saturable cell association of (125)I-HDL with the HKC-8 cell surface after 2 h.
      HKC-8 cells do not degrade apoA-I or other HDL-apoproteins. The specific cell
      association of lipid-free apoA-I is approx. 2-fold less than that observed for
      native HDL. Similarly, reconstituted HDL prepared from HDL-apoproteins and pure
      phospholipids also exhibits a low cell association with the HKC-8 cells. In
      contrast, reconstituted HDL prepared with the extracted lipids of HDL and pure
      apoA-I exhibits an even higher cell association than that observed with the
      native lipoprotein. A detailed characterization of the major lipid classes in
      reconstituted HDL shows that only cholesteryl ester increases the cell
      association of the recombinant particles. These results show that the cholesteryl
      ester content of HDL may play an important role in the re-absorptive salvage of
      HDL by the proximal tubule cells of the kidney.

PMID- 14711372
TI  - Structural model of carnitine palmitoyltransferase I based on the carnitine
      acetyltransferase crystal.
AB  - CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl
      CoA into palmitoylcarnitine in the presence of L-carnitine, facilitating the
      entry of fatty acids into mitochondria. We propose a 3-D (three-dimensional)
      structural model for L-CPT I (liver CPT I), based on the similarity of this
      enzyme to the recently crystallized mouse carnitine acetyltransferase. The model
      includes 607 of the 773 amino acids of L-CPT I, and the positions of carnitine,
      CoA and the palmitoyl group were assigned by superposition and docking analysis.
      Functional analysis of this 3-D model included the mutagenesis of several amino
      acids in order to identify putative catalytic residues. Mutants D477A, D567A and
      E590D showed reduced L-CPT I activity. In addition, individual mutation of amino
      acids forming the conserved Ser685-Thr686-Ser687 motif abolished enzyme activity
      in mutants T686A and S687A and altered K(m) and the catalytic efficiency for
      carnitine in mutant S685A. We conclude that the catalytic residues are His473 and
      Asp477, while Ser687 probably stabilizes the transition state. Several conserved
      lysines, i.e. Lys455, Lys505, Lys560 and Lys561, were also mutated. Only mutants
      K455A and K560A showed decreases in activity of 50%. The model rationalizes the
      finding of nine natural mutations in patients with hereditary L-CPT I
      deficiencies.

PMID- 14711373
TI  - Oxidative-stress-related proteome changes in Helicobacter pylori-infected human
      gastric mucosa.
AB  - Helicobacter pylori infection leads to gastroduodenal inflammation, peptic
      ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa
      from the patients with erosive gastritis, peptic ulcer or gastric cancer, which
      were either infected or not with H. pylori, was used to determine the
      differentially expressed proteins by H. pylori in the human gastric mucosa in
      order to investigate the pathogenic mechanism of H. pylori -induced gastric
      diseases. Prior to the experiment, the expression of the main 18 proteins were
      identified in the gastric mucosa and used for a proteome map of the human gastric
      mucosa. Using two-dimensional electrophoresis of the protein isolated from the H.
      pylori -infected tissues, Coomassie Brilliant Blue staining and computerized
      analysis of the stained gel, the expression of eight proteins were altered in the
      H. pylori -infected tissues compared with the non-infected tissues. MS analysis
      (matrix-assisted laser desorption/ionization-time of flight MS) of the tryptic
      fragment and a data search allowed the the identification of the four increased
      proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor,
      aldehyde dehydrogenase 2 and L-lactate dehydrogenase B chain) and the four
      decreased proteins (intracellular chloride channel protein 1, glutathione S
      transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori
      infection in the gastric mucosa. These proteins are related to cell
      proliferation, carcinogenesis, cytoskeletal function and cellular defence
      mechanism. The common feature is that these proteins are related to oxidative
      stress-mediated cell damage. In conclusion, the established gastric mucosal
      proteome map might be useful for detecting the disease-related protein changes.
      The H. pylori -induced alterations in protein expression demonstrate the
      involvement of oxidative stress in the pathogenesis of H. pylori -induced gastric
      diseases, including inflammation, ulceration and carcinogenesis.

PMID- 14711374
TI  - Is cost-effectiveness analysis preferred to severity of disease as the main
      guiding principle in priority setting in resource poor settings? The case of
      Uganda.
AB  - INTRODUCTION: Several studies carried out to establish the relative preference of
      cost-effectiveness of interventions and severity of disease as criteria for
      priority setting in health have shown a strong preference for severity of
      disease. These preferences may differ in contexts of resource scarcity, as in
      developing countries, yet information is limited on such preferences in this
      context. OBJECTIVE: This study was carried out to identify the key players in
      priority setting in health and explore their relative preference regarding cost
      effectiveness of interventions and severity of disease as criteria for setting
      priorities in Uganda. DESIGN: 610 self-administered questionnaires were sent to
      respondents at national, district, health sub-district and facility levels.
      Respondents included mainly health workers. We used three different simulations,
      assuming same patient characteristics and same treatment outcome but with varying
      either severity of disease or cost-effectiveness of treatment, to explore
      respondents' preferences regarding cost-effectiveness and severity. RESULTS:
      Actual main actors were identified to be health workers, development partners or
      donors and politicians. This was different from what respondents perceived as
      ideal. Above 90% of the respondents recognised the importance of both severity of
      disease and cost-effectiveness of intervention. In the three scenarios where they
      were made to choose between the two, a majority of the survey respondents
      assigned highest weight to treating the most severely ill patient with a less
      cost-effective intervention compared to the one with a more cost-effective
      intervention for a less severely ill patient. However, international development
      partners in in-depth interviews preferred the consideration of cost-effectiveness
      of intervention. CONCLUSIONS: In a survey among health workers and other actors
      in priority setting in Uganda, we found that donors are considered to have more
      say than the survey respondents found ideal. Survey respondents considered both
      severity of disease and cost-effectiveness important criteria for setting
      priorities, with severity of disease as the leading principle. This pattern of
      preferences is similar to findings in context with relatively more resources. In
      depth interviews with international development partners, showed that this group
      put relatively more emphasis on cost-effectiveness of interventions compared to
      severity of disease. These discrepancies in attitudes between national health
      workers and representatives from the donors require more investigation. The
      different attitudes should be openly debated to ensure legitimate decisions.

PMID- 14711375
TI  - MUC1: a multifunctional cell surface component of reproductive tissue epithelia.
AB  - MUC1 is a large, transmembrane mucin glycoprotein expressed at the apical surface
      of a variety of reproductive tract epithelia. Functions attributed to MUC1
      include those generally associated with mucins such as lubrication and hydration
      of cell surfaces as well as protection from microorganisms and degradative
      enzymes. In addition, MUC1 is an effective inhibitor of both cell-cell and cell
      extracellular matrix interactions in both normal and malignant contexts.
      Moreover, a series of recent studies has shown that the highly conserved
      cytoplasmic tail of MUC1 interacts specifically with a series of important signal
      transducing molecules including beta-catenin, Grb2 and erbB family members. MUC1
      expression in normal epithelia can be quite dynamic, varying in response to
      steroid hormone or cytokine influences. Following malignant transformation, MUC1
      often becomes highly overexpressed, loses its apical restriction, and displays
      aberrant glycosylation and altered mRNA splice variants. Regulation of MUC1
      expression can occur at the transcriptional level. In addition, post
      translational regulation of cell surface expression occurs via the activity of
      cell surface proteases or "sheddases" that release soluble forms of the large
      ectodomains. This review will briefly summarize studies of MUC1 expression and
      function in reproductive tissues with particular emphasis on the uterus. In
      addition, current knowledge of the mechanisms of MUC1 gene regulation, metabolic
      processing and potential signal transducing functions will be presented.

PMID- 14711378
TI  - Extracellular matrix: forum introduction.

PMID- 14711376
TI  - Syndecans in tumor cell adhesion and signaling.
AB  - Anchorage of cells to "heparin"--binding domains that are prevalent in
      extracellular matrix (ECM) components is thought to occur primarily through the
      syndecans, a four-member family of transmembrane heparan sulfate proteoglycans
      that communicate environmental cues from the ECM to the cytoskeleton and the
      signaling apparatus of the cell. Known activities of the syndecans trace to their
      highly conserved cytoplasmic domains and to their heparan sulfate chains, which
      can serve to regulate the signaling of growth factors and morphogens. However,
      several emerging studies point to critical roles for the syndecans' extracellular
      protein domains in tumor cell behavior to include cell adhesion and invasion.
      Although the mechanisms of these activities remain largely unknown, one
      possibility involves "co-receptor" interactions with integrins that may regulate
      integrin function and the cell adhesion-signaling phenotype. Thus, alterations in
      syndecan expression, leading to either overexpression or loss of expression, both
      of which take place in tumor cells, may have dramatic effects on tumor cell
      invasion.

PMID- 14711379
TI  - Small bowel gastrointestinal stromal tumours and ampullary cancer in Type 1
      neurofibromatosis.
AB  - BACKGROUND: Type 1 neurofibromatosis (NF-1) is an autosomal dominant disorder
      with variable penetrance; approximately 50% of cases present as new mutations
      CASE REPORT: We report a case of a 56 year-old man with Von Recklinghausen's
      disease, carcinoma of the ampulla of Vater and incidental benign gastrointestinal
      stromal tumours of the jejunum. CONCLUSIONS: Coexistence between ampullary
      carcinoid, ectopic pancreatic tissue in the jejunum and neurofibroma of the
      jejunum in NF-1 has been previously described however; the association of
      synchronous carcinoma of the ampulla of Vater and gastrointestinal stromal tumour
      of the jejunum in NF-1 has not been previously reported.

PMID- 14711377
TI  - Changes in extracellular matrix (ECM) and ECM-associated proteins in the
      metastatic progression of prostate cancer.
AB  - Prostate cancer (PCa) is no exception to the multi-step process of metastasis. As
      PCa progresses, changes occur within the microenvironments of both the malignant
      cells and their targeted site of metastasis, enabling the necessary responses
      that result in successful translocation. The majority of patients with
      progressing prostate cancers develop skeletal metastases. Despite advancing
      efforts in early detection and management, there remains no effective, long-term
      cure for metastatic PCa. Therefore, the elucidation of the mechanism of PCa
      metastasis and preferential establishment of lesions in bone is an intensive area
      of investigation that promises to generate new targets for therapeutic
      intervention. This review will survey what is currently know concerning PCa
      interaction with the extracellular matrix (ECM) and the roles of factors within
      the tumor and ECM microenvironments that contribute to metastasis. These will be
      discussed within the context of changes in expression and functional
      heterodimerization patterns of integrins, changes in ECM expression and
      reorganization by proteases facilitating invasion. In this context we also
      provide a brief summary of how growth factors (GFs), cytokines and regulatory
      signaling pathways favor PCa metastasis to bone.

PMID- 14711380
TI  - Inhibition of cell growth by EGR-1 in human primary cultures from malignant
      glioma.
AB  - BACKGROUND: The aim of this work was to investigate in vitro the putative role of
      EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the
      early passages in vitro of 17 primary cell lines grown from 3 grade III and from
      14 grade IV malignant astrocytoma explants. The explanted tumors were genetically
      characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and
      growth characteristics were examined. A recombinant adenovirus overexpressing EGR
      1 was tested in the primary cell lines. RESULTS: Low levels of EGR-1 protein were
      found in all primary cultures examined, with lower values present in grade IV
      tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1
      protein were significantly correlated to the amount of intracellular fibronectin,
      but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p =
      0.0082). Duplication time, plating efficiency, colony formation in agarose, and
      contact inhibition were also altered in the p53 mutated tumor cultures compared
      to those carrying wild-type p53. Growth arrest was achieved in both types of
      tumor within 1-2 weeks following infection with a recombinant adenovirus
      overexpressing EGR-1 but not with the control adenovirus. CONCLUSIONS:
      Suppression of EGR-1 is a common event in gliomas and in most cases this is
      achieved through down-regulation of gene expression. Expression of EGR-1 by
      recombinant adenovirus infection almost completely abolishes the growth of tumor
      cells in vitro, regardless of the mutational status of the p53 gene.

PMID- 14711381
TI  - Behavioral and antioxidant activity of a tosylbenz[g]indolamine derivative. A
      proposed better profile for a potential antipsychotic agent.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a major limitation of older
      antipsychotics. Newer antipsychotics have various other side effects such as
      weight gain, hyperglycemia, etc. In a previous study we have shown that an
      indolamine molecule expresses a moderate binding affinity at the dopamine D2 and
      serotonin 5-HT1A receptors in in vitro competition binding assays. In the present
      work, we tested its p-toluenesulfonyl derivative (TPBIA) for behavioral effects
      in rats, related to interactions with central dopamine receptors and its
      antioxidant activity. METHODS: Adult male Fischer-344 rats grouped as: i)
      Untreated rats: TPBIA was administered i.p. in various doses ii) Apomorphine
      treated rats: were treated with apomorphine (1 mg kg-1, i.p.) 10 min after the
      administration of TPBIA. Afterwards the rats were placed individually in the
      activity cage and their motor behaviour was recorded for the next 30 min The
      antioxidant potential of TPBIA was investigated in the model of in vitro non
      enzymatic lipid peroxidation. RESULTS: i) In non-pretreated rats, TPBIA reduces
      the activity by 39 and 82% respectively, ii) In apomorphine pretreated rats,
      TPBIA reverses the hyperactivity and stereotype behaviour induced by apomorphine.
      Also TPBIA completely inhibits the peroxidation of rat liver microsome
      preparations at concentrations of 0.5, 0.25 and 0.1 mM. CONCLUSION: TPBIA exerts
      dopamine antagonistic activity in the central nervous system. In addition, its
      antioxidant effect is a desirable property, since TD has been partially
      attributed, to oxidative stress. Further research is needed to test whether TPBIA
      may be used as an antipsychotic agent.

PMID- 14711382
TI  - Heterotrimeric G protein subunits are located on rat liver endosomes.
AB  - BACKGROUND: Rat liver endosomes contain activated insulin receptors and
      downstream signal transduction molecules. We undertook these studies to determine
      whether endosomes also contain heterotrimeric G proteins that may be involved in
      signal transduction from G protein-coupled receptors. RESULTS: By Western
      blotting Gsalpha, Gialpha1,2, Gialpha3 and Gbeta were enriched in both
      canalicular (CM) and basolateral (BLM) membranes but also readily detectable on
      three types of purified rat liver endosomes in the order recycling receptor
      compartment (RRC) > compartment for uncoupling of receptor and ligand (CURL) >
      multivesicular bodies (MVB) >> purified secondary lysosomes. Western blotting
      with antibodies to Na, K-ATPase and to other proteins associated with plasma
      membranes and intracellular organelles indicated this was not due to
      contamination of endosome preparations by CM or BLM. Adenylate cyclase (AC) was
      also identified on purified CM, BLM, RRC, CURL and MVB. Percoll gradient
      fractionation of liver postnuclear supernatants demonstrated co-occurrence of
      endosomes and heterotrimeric G protein subunits in fractions with little plasma
      membrane markers. By confocal microscopy, punctate staining for Gsalpha, Gialpha3
      and Gbeta corresponded to punctate areas of endocytosed Texas red-dextran in
      hepatocytes from control and cholera toxin-treated livers. CONCLUSION: We
      conclude that heterotrimeric G protein subunits as well as AC likely traffic into
      hepatocytes on endosome membranes, possibly generating downstream signals
      spatially separate from signalling generated at the plasma membrane, analogous to
      the role(s) of internalized insulin receptors.

PMID- 14711386
TI  - High-throughput screening in academia: the Harvard experience.
AB  - To identify small-molecule modulators of biologic systems, academic scientists
      are beginning to use high-throughput screening (HTS) approaches that have
      traditionally been used only in industry. The HTS laboratories that are being
      established in universities, while differing in details of staffing, equipment,
      and size, have all been created to attain 1 or more of 3 principal goals: drug
      discovery, chemical genetics, or training. This article will examine the role
      that these activities play in 4 HTS laboratories that have been created within
      the academic community of Harvard Medical School and its affiliated institutions.
      First, the 3 activities will be defined with special attention paid to describing
      the impact they are having on how academic biologic science is conducted today.
      Next, the histories and operations of the 4 Harvard laboratories are reviewed. In
      the course of these summaries, emphasis is placed on understanding the
      motivational role that the 3 activities initially played in the creation of the 4
      Harvard facilities and the roles that the activities continue to play in their
      day-to-day operations. Finally, several concerns are identified that must be
      attended to for the successful establishment and operation of an academic
      biologic science that has yet to be fully determined. HTS has the ability to
      provide the tools to test previously untestable hypotheses and can thereby allow
      the discovery of the unanticipated and the truly novel.

PMID- 14711384
TI  - Immortalization of mouse myogenic cells can occur without loss of p16INK4a,
      p19ARF, or p53 and is accelerated by inactivation of Bax.
AB  - BACKGROUND: Upon serial passaging of mouse skeletal muscle cells, a small number
      of cells will spontaneously develop the ability to proliferate indefinitely while
      retaining the ability to differentiate into multinucleate myotubes. Possible gene
      changes that could underlie myogenic cell immortalization and their possible
      effects on myogenesis had not been examined. RESULTS: We found that
      immortalization occurred earlier and more frequently when the myogenic cells
      lacked the pro-apoptotic protein Bax. Furthermore, myogenesis was altered by Bax
      inactivation as Bax-null cells produced muscle colonies with more nuclei than
      wild-type cells, though a lower percentage of the Bax-null nuclei were
      incorporated into multinucleate myotubes. In vivo, both the fast and slow
      myofibers in Bax-null muscles had smaller cross-sectional areas than those in
      wild-type muscles. After immortalization, both Bax-null and Bax-positive myogenic
      cells expressed desmin, retained the capacity to form multinucleate myotubes,
      expressed p19ARF protein, and retained p53 functions. Expression of p16INK4a,
      however, was found in only about half of the immortalized myogenic cell lines.
      CONCLUSIONS: Mouse myogenic cells can undergo spontaneous immortalization via a
      mechanism that can include, but does not require, loss of p16INK4a, and also does
      not require inactivation of p19ARF or p53. Furthermore, loss of Bax, which
      appears to be a downstream effector of p53, accelerates immortalization of
      myogenic cells and alters myogenesis.

PMID- 14711387
TI  - A reporter system for reverse transfection cell arrays.
AB  - The incredible speed of gene cloning and sequencing brought about by the genomic
      revolution has begun to outpace conventional gene discovery approaches in the
      pharmaceutical industry. High-throughput approaches for studying gene function in
      vivo are greatly needed. One potential answer to this challenge is reverse
      transfection, a high-throughput gene expression method for examining the function
      of hundreds to thousands of genes in parallel. One limitation of reverse
      transfection technology is the need for posttransfection processing of the arrays
      to analyze the activity of the expressed proteins. The authors have investigated
      the use of a reporter construct cotransfected with other genes of interest to
      monitor and screen gene function on reverse transfection microarrays. They
      developed a serum response element (SRE) reporter linked to the green fluorescent
      protein (GFP) that is cotransfected with target genes on reverse transfection
      arrays for monitoring mitogen-activated protein (MAP) kinase signaling by
      multiple targets in parallel. The authors show that this reporter system is able
      to detect inhibition of upstream MAP kinase signaling proteins by the MEK
      inhibitor U0126. The ability to monitor the activity of multiple signaling
      proteins in a multiwell format suggests the utility of reverse transfection
      reporter arrays for high-throughput screening applications.

PMID- 14711388
TI  - Statistical and graphical methods for quality control determination of high
      throughput screening data.
AB  - High-throughput screening (HTS) is used in modern drug discovery to screen
      hundreds of thousands to millions of compounds on selected protein targets. It is
      an industrial-scale process relying on sophisticated automation and state-of-the
      art detection technologies. Quality control (QC) is an integral part of the
      process and is used to ensure good quality data and mini mize assay variability
      while maintaining assay sensitivity. The authors describe new QC methods and show
      numerous real examples from their biologist-friendly Stat Server HTS application,
      a custom-developed software tool built from the commercially available S-PLUS and
      Stat Server statistical analysis and server software. This system remotely
      processes HTS data using powerful and sophisticated statistical methodology but
      insulates users from the technical details by outputting results in a variety of
      readily interpretable graphs and tables. It allows users to visualize HTS data
      and examine assay performance during the HTS campaign to quickly react to or
      avoid quality problems.

PMID- 14711389
TI  - Improved statistical methods for hit selection in high-throughput screening.
AB  - High-throughput screening (HTS) plays a central role in modern drug discovery,
      allowing the rapid screening of large compound collections against a variety of
      putative drug targets. HTS is an industrial-scale process, relying on
      sophisticated automation, control, and state-of-the art detection technologies to
      organize, test, and measure hundreds of thousands to millions of compounds in
      nano- to microliter volumes. Despite this high technology, hit selection for HTS
      is still typically done using simple data analysis and basic statistical methods.
      The authors discuss in this article some shortcomings of these methods and
      present alternatives based on modern methods of statistical data analysis. Most
      important, they describe and show numerous real examples from the biologist
      friendly Stat Server HTS application (SHS), a custom-developed software tool
      built on the commercially available S-PLUS and StatServer statistical analysis
      and server software. This system remotely processes HTS data using powerful and
      sophisticated statistical methodology but insulates users from the technical
      details by outputting results in a variety of readily interpretable graphs and
      tables.

PMID- 14711390
TI  - A modular, fully integrated ultra-high-throughput screening system based on
      confocal fluorescence analysis techniques.
AB  - The rapid increase in size of compound libraries, as well as new targets emerging
      from the Human Genome Project, require progress in ultra-high-throughput
      screening (uHTS) systems. In a joint effort with scientists and engineers from
      the biotech and the pharmaceutical industry, a modular, fully integrated system
      for miniaturized uHTS was developed. The goal was to achieve high data quality in
      small assay volumes (1-4 microL) combined with reliable and unattended operation.
      Two new confocal fluorescence readers have been designed. One of the instruments
      is a 4-channel confocal fluorescence reader, measuring with 4 objectives in
      parallel. The fluorescence readout is based on single-molecule detection methods,
      allowing high sensitivity at low tracer concentrations and delivering an
      information-rich output. The other instrument is a confocal fluorescence imaging
      reader, where the images are analyzed in terms of generic patterns and quantified
      in units of intensity per pixel. Both readers are spanning the application range
      from assays with isolated targets in homogenous solution or membrane vesicle
      based assays (4-channel reader) to cell-based assays (imaging reader). Results
      from a comprehensive test on these assay types demonstrate the high quality and
      robustness of this screening system.

PMID- 14711391
TI  - Fluorescence imaging of electrically stimulated cells.
AB  - Designing high-throughput screens for voltage-gated ion channels has been a
      tremendous challenge for the pharmaceutical industry because channel activity is
      dependent on the transmembrane voltage gradient, a stimulus unlike ligand binding
      to G-protein-coupled receptors or ligand-gated ion channels. To achieve an
      acceptable throughput, assays to screen for voltage-gated ion channel modulators
      that are employed today rely on pharmacological intervention to activate these
      channels. These interventions can introduce artifacts. Ideally, a high-throughput
      screen should not compromise physiological relevance. Hence, a more appropriate
      method would activate voltage-gated ion channels by altering plasma membrane
      potential directly, via electrical stimulation, while simultaneously recording
      the operation of the channel in populations of cells. The authors present
      preliminary results obtained from a device that is designed to supply precise and
      reproducible electrical stimuli to populations of cells. Changes in voltage-gated
      ion channel activity were monitored using a digital fluorescent microscope. The
      prototype electric field stimulation (EFS) device provided real-time analysis of
      cellular responsiveness to physiological and pharmacological stimuli. Voltage
      stimuli applied to SK-N-SH neuroblastoma cells cultured on the EFS device evoked
      membrane potential changes that were dependent on activation of voltage-gated
      sodium channels. Data obtained using digital fluorescence microscopy suggests
      suitability of this system for HTS.

PMID- 14711392
TI  - Putting thought to paper: a microARCS protease screen.
AB  - In micro-arrayed compound screening (microARCS), an agarose gel is used as a
      reaction vessel that maintains humidity and compound location as well as being a
      handling system for reagent addition. Two or more agarose gels may be used to
      bring test compounds, targets, and reagents together, relying on the pore size of
      the gel matrix to regulate diffusion of reactants. It is in the microenvironment
      of the agarose matrix that all the components of an enzymatic reaction interact
      and result in inhibitable catalytic activity. In an effort to increase the
      throughput of microARCS-based screens, reduce the effort involved in manipulating
      agarose gels, and reduce costs, blotter paper was used rather than a second
      agarose gel to introduce a substrate to a gel containing a target enzyme. In this
      assay, the matrix of the blotter paper did not prevent the substrate from
      diffusing into the enzyme gel. The compound density of the microARCS format, the
      ease of manipulating sheets of paper for reagent addition, and a scheduled
      protocol for running multiple gels allowed for a throughput capacity of more than
      200,000 tests per hour. A protease assay was developed and run in the microARCS
      format at a rate of 200,000 tests per hour using blotter paper to introduce the
      substrate. Picks in the primary screen were retested in the microARCS format at a
      density of 384 compounds per sheet. IC(50) values were confirmed in a 96-well
      plate format. The screen identified several small molecule inhibitors of the
      enzyme. The details of the screening format and the analysis of the hits from the
      screen are presented.

PMID- 14711393
TI  - A dual luciferase multiplexed high-throughput screening platform for protein
      protein interactions.
AB  - To study the biology of regulators of G-protein signaling (RGS) proteins and to
      facilitate the identification of small molecule modulators of RGS proteins, the
      authors recently developed an advanced yeast 2-hybrid (YTH) assay format for
      GalphaZ and RGS-Z1. Moreover, they describe the development of a multiplexed
      luciferase-based assay that has been successfully adapted to screen large numbers
      of small molecule modulators of protein-protein interactions. They generated and
      evaluated 2 different luciferase reporter gene systems for YTH interactions, a
      Gal4 responsive firefly luciferase reporter gene and a Gal4 responsive Renilla
      luciferase reporter gene. Both the firefly and Renilla luciferase reporter genes
      demonstrated a 40- to 50-fold increase in luminescence in strains expressing
      interacting YTH fusion proteins versus negative control strains. Because the
      firefly and Renilla luciferase proteins have different substrate specificity, the
      assays were multiplexed. The multiplexed luciferase-based YTH platform adds
      speed, sensitivity, simplicity, quantification, and efficiency to YTH high
      throughput applications and therefore greatly facilitates the identification of
      small molecule modulators of protein-protein interactions as tools or potential
      leads for drug discovery efforts.

PMID- 14711394
TI  - Rapid and automated fluorescence-linked immunosorbent assay for high-throughput
      screening of HIV-1 fusion inhibitors targeting gp41.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 plays
      an important role in the virus entry. During the process of fusion between the
      viral and target cell membranes, the N- and C-terminal heptad repeat (HR) regions
      of the gp41 extracellular domain associate to form a 6-helical bundle,
      corresponding to the fusion-active gp41 core. Any compound that blocks the gp41 6
      helix bundle formation between the N- and C-peptides, which are derived from the
      N- and C-terminal HR regions, respectively, may inhibit HIV-1 mediated membrane
      fusion. Based on this principle, we previously established a sandwich enzyme
      linked immunosorbent assay (ELISA) for drug screening by using the N-peptide N36
      and the C-peptide C34 and a monoclonal antibody (NC-1) which specifically
      recognizes the gp41 6-helix bundle. In the present study, a fluorescence-linked
      immunosorbent assay (FLISA) was developed by using fluorescein isothiocyanate
      (FITC)-conjugated C34 to replace C34 and by directly detecting fluorescence
      intensity instead of more complicated enzymatic reaction. Compared with the
      sandwich ELISA, this FLISA has similar sensitivity and specificity, but it is
      much more rapid, economic and convenient. Using an Integrated Robotic Sample
      Processing System, this assay has been applied for high-throughput screening of
      organic compounds on a large scale for HIV-1 fusion inhibitors targeting gp41.

PMID- 14711395
TI  - Determining appropriate substrate conversion for enzymatic assays in high
      throughput screening.
AB  - It is generally accepted that the conversion of substrate should be kept at less
      than 10% of the total substrate used when studying enzyme kinetics. However, 10%
      or less substrate conversion often will not produce sufficient signal changes
      required for robust high-throughput screening (HTS). To increase the signal-to
      background ratio, HTS is often performed at higher than 10% substrate conversion.
      Because the consequences of high substrate conversion are poorly understood, the
      screening results are sometimes questioned by enzymologists. The quality of an
      assay is judged by the ability to detect an inhibitor under HTS conditions, which
      depends on the robustness of the primary detection signal (Z factor) and the
      sensitivity to an inhibitor. The assay sensitivity to an inhibitor is reflected
      in the observed IC(50) value or percent inhibition at a fixed compound
      concentration when single-point data are collected. The major concern for an
      enzymatic assay under high substrate conversion is that the sensitivity of the
      screen may be compromised. Here we derive the relationship between the IC(50)
      value for a given inhibitor and the percentage of substrate conversion using a
      first-order kinetic model under conditions that obey Henri-Michaelis-Menten
      kinetics. The derived theory was further verified experimentally with a cAMP
      dependent protein kinase. This model provides guidance for assay developers to
      choose an appropriate substrate conversion in designing an enzymatic assay,
      balancing the needs for robust signal and sensitivity to inhibitors.

PMID- 14711396
TI  - Development of quantitative detection assays for CYR61 as a new marker for benign
      prostatic hyperplasia.
AB  - Among urological diseases, benign prostatic hyperplasia (BPH) exhibits a high
      morbidity rate, afflicting approximately 50% of men older than age 50 years.
      Despite intense research efforts over the past decades, the etiology and
      mechanisms of BPH progression are only poorly understood. Employing
      oligonucleotide microarrays, the authors analyzed the gene expression profiles in
      normal and BPH prostate samples and found that CYR61, an immediate early gene, is
      markedly overexpressed in BPH. To quantify cellular CYR61 mRNA expression
      directly, the authors developed an assay using branched-chain DNA (bDNA)
      technology. A human prostatic epithelial cell line, BRF-55T, derived from a BPH
      patient, was treated with fetal bovine serum to stimulate gene expression, and
      then the induction profile of the CYR61 mRNA in these serum-stimulated cells was
      quantitated using both bDNA and quantitative reverse transcriptase-PCR (RT-PCR).
      The results obtained with the 2 detection systems were found to be very similar.
      The bDNA assay was also found to be sensitive and highly reproducible. To the
      authors' knowledge, this is the first time that identifying CYR61 as a novel
      marker for BPH and its quantitation has been reported. These detection methods
      not only may be useful for diagnostic purposes but may also be used to identify
      suppressors of CYR61 expression for BPH therapy employing high-throughput
      screening assays.

PMID- 14711397
TI  - The effect of triton concentration on the activity of undecaprenyl pyrophosphate
      synthase inhibitors.
AB  - Undecaprenyl pyrophosphate synthase (UPPS) catalyzes the consecutive condensation
      of 8 molecules of isopentenyl pyrophosphate with farnesyl pyrophosphate to yield
      C55-undecaprenyl pyrophosphate, which is required for bacterial cell wall
      synthesis. UPPS is found in both gram-positive and gram-negative bacteria, and
      based on the differences between bacterial variants of UPPS and their human
      counterpart, dolicopyrophosphate synthase, it was identified as an attractive
      antibacterial target. An assay, which monitors the release of Pi by coupling the
      UPPS catalyzed reaction with inorganic pyrophosphatase, was employed to conduct
      an HTS campaign using an inhouse collection of compounds. A direct assay
      measuring the incorporation of 14C-IPP (isopentenyl pyrophosphate) was used as a
      secondary assay to evaluate the high-throughput screening (HTS) hits. From the
      HTS campaign, a few classes of UPPS inhibitors were identified. During the
      process of hit evaluation by the direct assay, the authors observed that Triton,
      an essential factor for the enzyme activity and accurate formation of the natural
      product, dramatically altered the inhibitory activity of a particular class of
      compounds. Above its critical micellar concentration (CMC), Triton abolished the
      inhibitory activity of these compounds. Further research will be required to
      establish the biophysical phenomenon that causes this effect. Meanwhile, it can
      be speculated that Triton (and other detergents) above CMC may hinder the
      identification in screening compounds of certain classes of hits.

PMID- 14711408
TI  - Dynamic actin patterns and Arp2/3 assembly at the substrate-attached surface of
      motile cells.
AB  - BACKGROUND: In the cortical region of motile cells, the actin network rapidly
      reorganizes as required for movement in various directions and for cell-to
      substrate adhesion. The analysis of actin network dynamics requires the
      combination of high-resolution imaging with a specific fluorescent probe that
      highlights the filamentous actin structures in live cells. RESULTS: Combining
      total internal reflection fluorescence (TIRF) microscopy with a method for
      labeling actin filaments, we analyze the dynamics of actin patterns in the highly
      motile cells of Dictyostelium. A rapidly restructured network of single or
      bundled actin filaments provides a scaffold for the assembly of differentiated
      actin complexes. Recruitment of the Arp2/3 complex characterizes stationary foci
      with a lifetime of 7-10 s and traveling waves. These structures are also formed
      in the absence of myosin-II. Arp2/3-actin assemblies similar to those driving the
      protrusion of a leading edge form freely at the inner face of the plasma
      membrane. CONCLUSIONS: The actin system of highly motile cells runs far from
      equilibrium and generates a multitude of patterns within a dynamic filamentous
      network. Traveling waves are the most complicated patterns based on recruitment
      of the Arp2/3 complex. They are governed by the propagated induction of actin
      polymerization. We hypothesize that the actin system autonomously generates
      primordia of specialized structures such as phagocytic cups or lamellipodia.
      These primordia would represent an activated state of the actin system and enable
      cells to respond within seconds to local stimuli by chemotaxis or phagocytic-cup
      formation.

PMID- 14711409
TI  - Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck
      triggers localized actin polymerization.
AB  - BACKGROUND: SH2/SH3 adaptor proteins play a critical role in tyrosine kinase
      signaling pathways, regulating essential cell functions by increasing the local
      concentration or altering the subcellular localization of downstream effectors.
      The SH2 domain of the Nck adaptor can bind tyrosine-phosphorylated proteins,
      while its SH3 domains can modulate actin polymerization by interacting with
      effectors such as WASp/Scar family proteins. Although several studies have
      implicated Nck in regulating actin polymerization, its role in living cells is
      not well understood. RESULTS: We used an antibody-based system to experimentally
      modulate the local concentration of Nck SH3 domains on the plasma membrane of
      living cells. Clustering of fusion proteins containing all three Nck SH3 domains
      induced localized polymerization of actin, including the formation of actin tails
      and spots, accompanied by general cytoskeletal rearrangements. All three Nck SH3
      domains were required, as clustering of individual SH3 domains or a combination
      of the two N-terminal Nck SH3 domains failed to promote significant local
      polymerization of actin in vivo. Changes in actin dynamics induced by Nck SH3
      domain clustering required the recruitment of N-WASp, but not WAVE1, and were
      unaffected by downregulation of Cdc42. CONCLUSIONS: We show that high local
      concentrations of Nck SH3 domains are sufficient to stimulate localized, Cdc42
      independent actin polymerization in living cells. This study provides strong
      evidence of a pivotal role for Nck in directly coupling ligand-induced tyrosine
      phosphorylation at the plasma membrane to localized changes in organization of
      the actin cytoskeleton through a signaling pathway that requires N-WASp.

PMID- 14711410
TI  - Relative contribution of DNA repair, cell cycle checkpoints, and cell death to
      survival after DNA damage in Drosophila larvae.
AB  - BACKGROUND: Components of the DNA damage checkpoint are essential for surviving
      exposure to DNA damaging agents. Checkpoint activation leads to cell cycle
      arrest, DNA repair, and apoptosis in eukaryotes. Cell cycle regulation and DNA
      repair appear essential for unicellular systems to survive DNA damage. The
      relative importance of these responses and apoptosis for surviving DNA damage in
      multicellular organisms remains unclear. RESULTS: After exposure to ionizing
      radiation, wild-type Drosophila larvae regulate the cell cycle and repair DNA;
      grp (DmChk1) mutants cannot regulate the cell cycle but repair DNA; okra
      (DmRAD54) mutants regulate the cell cycle but are deficient in repair of double
      strand breaks (DSB); mei-41 (DmATR) mutants cannot regulate the cell cycle and
      are deficient in DSB repair. All undergo radiation-induced apoptosis. p53 mutants
      regulate the cell cycle but fail to undergo apoptosis. Of these, mutants
      deficient in DNA repair, mei-41 and okra, show progressive degeneration of
      imaginal discs and die as pupae, while other genotypes survive to adulthood after
      irradiation. Survival is accompanied by compensatory growth of imaginal discs via
      increased nutritional uptake and cell proliferation, presumably to replace dead
      cells. CONCLUSIONS: DNA repair is essential for surviving radiation as expected;
      surprisingly, cell cycle regulation and p53-dependent cell death are not. We
      propose that processes resembling regeneration of discs act to maintain tissues
      and ultimately determine survival after irradiation, thus distinguishing
      requirements between muticellular and unicellular eukaryotes.

PMID- 14711411
TI  - BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans.
AB  - Inherited germline mutations in the tumor suppressor gene BRCA1 predispose
      individuals to early onset breast and ovarian cancer. BRCA1 together with its
      structurally related partner BARD1 is required for homologous recombination and
      DNA double-strand break repair, but how they perform these functions remains
      elusive. As part of a comprehensive search for DNA repair genes in C. elegans, we
      identified a BARD1 ortholog. In protein interaction screens, Ce-BRD-1 was found
      to interact with components of the sumoylation pathway, the TACC domain protein
      TAC-1, and most importantly, a homolog of mammalian BRCA1. We show that animals
      depleted for either Ce-brc-1 or Ce-brd-1 display similar abnormalities, including
      a high incidence of males, elevated levels of p53-dependent germ cell death
      before and after irradiation, and impaired progeny survival and chromosome
      fragmentation after irradiation. Furthermore, depletion of ubc-9 and tac-1 leads
      to radiation sensitivity and a high incidence of males, respectively, potentially
      linking these genes to the C. elegans BRCA1 pathway. Our findings support a
      shared role for Ce-BRC-1 and Ce-BRD-1 in C. elegans DNA repair processes, and
      this role will permit studies of the BRCA1 pathway in an organism amenable to
      rapid genetic and biochemical analysis.

PMID- 14711412
TI  - Evidence for reproductive isolation between cave bear populations.
AB  - The European cave bear (Ursus spelaeus), which became extinct around 15,000 years
      ago, had several morphologically different forms. Most conspicuous of these were
      small Alpine cave bears found at elevations of 1,600 to 2,800 m. Whereas some
      paleontologists have considered these bears a distinct form, or even a distinct
      species, others have disputed this. By a combination of morphological and genetic
      methods, we have analyzed a population of small cave bears from Ramesch Cave
      (2,000 m altitude) and one of larger cave bears from Gamssulzen Cave (1,300 m),
      situated approximately 10 km apart in the Austrian Alps (Figure 1A). We find no
      evidence of mitochondrial gene flow between these caves during the 15,000 years
      when they were both occupied by cave bears, although mitochondrial DNA sequences
      identical to those from Gamssulzen Cave could be recovered from a site located
      about 200 km to the south in Croatia. We also find no evidence that the
      morphology of the bears in the two caves changed to become more similar over
      time. We suggest that the two cave bear forms may have represented two
      reproductively isolated subspecies or species.

PMID- 14711413
TI  - Spermatozoal traits and sperm competition in Atlantic salmon: relative sperm
      velocity is the primary determinant of fertilization success.
AB  - Sperm competition occurs when sperm from more than one male compete for
      fertilizations. This form of post-copulatory sexual selection is recognized as a
      significant and widespread force in the evolution of male reproductive biology
      and as a key determinant of differential male reproductive success. Despite its
      importance, however, detailed mechanisms of sperm competition at the gamete level
      remain poorly understood. Here, we use natural variation in spermatozoal traits
      among wild Atlantic salmon (Salmo salar), a species naturally adapted to sperm
      competition, to examine how the relative influences of sperm (i) number, (ii)
      velocity, (iii) longevity, and (iv) total length determine sperm competition
      success. Atlantic salmon fertilize externally, and we were therefore able to
      conduct controlled in vitro fertilization competitions while concurrently
      measuring spermatozoal traits within the aqueous micro-environment to which
      salmon gametes are naturally adapted. Microsatellite DNA fingerprinting revealed
      that a male's relative sperm velocity was the primary determinant of sperm
      competition success. There was no significant relationship between fertilization
      success and either relative sperm number or total length; sperm longevity showed
      an inverse relationship with competition success. These relationships were
      consistent for two experimental repeats of the in vitro fertilization
      competitions. Our results therefore show, under the natural microenvironment for
      salmon gametes, that relative sperm velocity is a key spermatozoal component for
      sperm competition success. Atlantic salmon sperm can be considered to enter a
      competition analogous to a race in which the fastest sperm have the highest
      probability of success.

PMID- 14711414
TI  - Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm
      specification cascade.
AB  - pou5f1, also known as Oct4, is required to establish the pluripotent cell
      population necessary for embryogenesis in mouse. Additional roles during
      development, including endoderm formation, have been proposed. In zebrafish, the
      zygotic pou5f1/pou2 mutant spiel ohne grenzen (spg) shows neural plate patterning
      defects and reduced endoderm at the tailbud stage. To investigate the function of
      maternal and early zygotic pou5f1 expression, we rescued zygotic spg(m793)
      mutants by injecting pou5f1 mRNA at the one-cell stage and raised them into
      fertile homozygous spg(m793) adults that mate to produce maternal-zygotic spg
      (MZspg) mutant embryos. Although neurectoderm, mesoderm, and germ cells develop
      in MZspg mutants, gastrulation is delayed and proceeds abnormally. Further, MZspg
      mutants do not maintain expression of sox32/casanova, express little or no sox17,
      and fail to develop endodermal tissue. Constitutively active Nodal receptor TARAM
      A or sox32 overexpression induces ubiquitous sox17 expression in wild-type
      embryos, but not in MZspg mutants. Overexpression of a Pou5f1-VP16 activator
      fusion protein can rescue gastrulation and endodermal tissues in MZspg mutants.
      We propose that pou5f1 plays an activating role in zebrafish endodermal
      development, where it maintains sox32 expression during gastrulation and acts
      with sox32 to induce sox17 expression in endodermal precursor cells.

PMID- 14711415
TI  - In vivo dynamics of the rough deal checkpoint protein during Drosophila mitosis.
AB  - Rough Deal (Rod) and Zw10 are components of a complex required for the metazoan
      metaphase checkpoint and for recruitment of dynein/dynactin to the kinetochore.
      The Rod complex, like most classical metaphase checkpoint components, forms part
      of the outer domain of unattached kinetochores. Here we analyze the dynamics of a
      GFP-Rod chimera in living syncytial Drosophila embryos. Uniquely among checkpoint
      proteins, GFP-Rod robustly streams from kinetochores along microtubules, from the
      time of chromosome attachment until anaphase onset. Prometaphase and metaphase
      kinetochores continuously recruit new Rod, thus feeding the current. Rod flux
      from kinetochores appears to require biorientation but not tension because it
      continues in the presence of taxol. As with Mad2, kinetochore- and spindle
      associated Rod rapidly turns over with free cytosolic Rod, both during normal
      mitosis and after colchicine treatment, with a t1/2 of 25-45 s. GFP-Rod
      coimmunoprecipitates with dynein/dynactin, and in the absence of microtubules
      both Rod and dynactin accumulate on kinetochores. Nevertheless, Rod and
      dynein/dynactin behavior are distinguishable. We propose that the Rod complex is
      a major component of the fibrous corona and that the recruitment of Rod during
      metaphase is required to replenish kinetochore dynein after checkpoint conditions
      have been satisfied but before anaphase onset.

PMID- 14711416
TI  - The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channel regulate
      thermosensory neuron gene expression and function in C. elegans.
AB  - The cultivation temperature (T(c)) modulates the thermosensory responses
      exhibited by C. elegans on thermal gradients. The AFD sensory neurons are
      essential for thermosensory behaviors, but the molecular mechanisms by which
      temperature is sensed and the memory of the T(c) is encoded are unknown. Here, we
      show that the CMK-1 Ca2+/calmodulin-dependent protein kinase I (CaMKI) and the
      TAX-4 cyclic nucleotide-gated channel regulate gene expression, morphology, and
      functions of the AFD thermosensory neurons. Mutations in cmk-1 and tax-4 result
      in temperature-dependent defects in AFD-specific gene expression, and TAX-4
      functions are required during larval stages to maintain gene expression in the
      adult. CMK-1 and TAX-4 act cell autonomously to regulate AFD-mediated
      thermosensory behaviors. The molecular requirements for CMK-1 activity in the AFD
      neurons appear to be distinct from those previously described. We propose that
      the activation of distinct programs of AFD-specific gene expression at different
      temperatures by CMK-1 and TAX-4 enables C. elegans to sense and/or encode a
      memory for the T(c).

PMID- 14711417
TI  - A potential tension-sensing mechanism that ensures timely anaphase onset upon
      metaphase spindle orientation.
AB  - The spindle orientation checkpoint (SOC) in fission yeast has been proposed to
      delay metaphase-to-anaphase transition when the spindle poles are misaligned with
      respect to the long axis of the cell. This checkpoint is activated in the absence
      of either an actomyosin division ring or astral microtubules. Although the SOC
      could be overridden in the absence of the transcription factor Atf1p, its
      mechanistic nature remained unclear. Here, we show that the SOC-triggered
      metaphase delay depends on a subset of the spindle assembly checkpoint (SAC)
      components Mph1p and Bub1p. Based on this finding and a detailed imaging of the
      spindle orientation process, we hypothesized that the spindle pole might contain
      proteins capable of sensing the achievement of spindle alignment. We identified
      the kendrin-like spindle pole body resident Pcp1p as a candidate molecule. A
      targeted mutation in its central domain specifically triggered the SOC in spite
      of the presence of oriented spindles, causing a metaphase delay that could be
      relieved in the absence of Mph1p, Bub1p, and Atf1p. Thus, Pcp1p might provide a
      link between the mechanical process of spindle alignment and the signal
      transduction that initiates anaphase.

PMID- 14711418
TI  - The Drosophila MOS ortholog is not essential for meiosis.
AB  - In metazoan oocytes, a metaphase arrest coordinates the completion of meiosis
      with fertilization. Vertebrate mos maintains the metaphase II arrest of mature
      oocytes and prevents DNA replication between the meiotic divisions. We identified
      a Drosophila homolog of mos and showed it to be the mos ortholog by two
      additional criteria. The dmos transcripts are present in Drosophila oocytes but
      not embryos, and injection of dmos into Xenopus embryos blocks mitosis and
      elevates active MAPK levels. In Drosophila, MAPK is activated in oocytes,
      consistent with a role in meiosis. We generated deletions of dmos and found that,
      as in vertebrates, dmos is responsible for the majority of MAPK activation.
      Unexpectedly, the oocytes that do mature complete meiosis normally and produce
      fertilized embryos that develop, although there is a reduction in female
      fertility and loss of some oocytes by apoptosis. Therefore, Drosophila contains a
      mos ortholog that activates a MAPK cascade during oogenesis and is nonessential
      for meiosis. This could be because there are redundant pathways regulating
      meiosis, because residual, low levels of active MAPK are sufficient, or because
      active MAPK is dispensable for meiosis in Drosophila. These results highlight the
      complexity of meiotic regulation that evolved to ensure accurate control over the
      reproductive process.

PMID- 14711419
TI  - Push to bolster women's careers.

PMID- 14711420
TI  - Jeff Stock.

PMID- 14711422
TI  - ATP-gated P2X channels.

PMID- 14711423
TI  - Theoretical embryology: a route to extinction?

PMID- 14711426
TI  - Cellular differentiation: the violin strikes up another tune.
AB  - A switch in cellular identity in budding yeast requires the ubiquitin-dependent
      elimination of pre-existing master regulators encoded by the MAT locus. Failure
      to disassemble the prior state not only impairs the cell type transition but
      imparts a hybrid cellular fate. This theme will undoubtedly arise in many
      developmental and disease contexts.

PMID- 14711427
TI  - Visual system: how is the retina wired up to the cortex?
AB  - A single retinal output neuron transmits to primary visual cortex through
      multiple pathways with different strengths. A new study in which activity was
      simultaneously recorded in pairs of retinal and cortical neurons provides
      evidence that these pathways converge on a single cortical neuron.

PMID- 14711425
TI  - Long-term persistence of bacterial DNA.

PMID- 14711428
TI  - Dorsoventral patterning: a serpin pinned down at last.
AB  - Dorsoventral patterning in Drosophila has long been known to involve a cascade of
      proteases, held in the inactive zymogen state prior to signaling. At long last,
      the prediction that a protease inhibitor is involved in this pathway has been
      shown to be true, with the identification of a serpin that plays a key part in
      Drosophila embryonic patterning.

PMID- 14711429
TI  - Axon guidance: morphogens show the way.
AB  - Hedgehog and Wnt family proteins can act as classic developmental morphogens to
      pattern a field of nai;ve cells. Surprising new studies show that members of
      these same protein families also act as guidance cues for growing axons in the
      developing nervous system.

PMID- 14711430
TI  - Plant immunity: the origami of receptor activation.
AB  - Mutations in plant cytosolic HSP90 genes have been found to impair the immune
      responses triggered by host pathogen receptors. HSP90 links the plant receptors
      to other components essential for receptor function. The new findings suggest
      mechanistic parallels with steroid receptor regulation in animals.

PMID- 14711431
TI  - Cellular clocks: coupled circadian and cell division cycles.
AB  - Gating of cell division by the circadian clock is well known, yet its mechanism
      is little understood. Genetically tractable model systems have led to new
      hypotheses and questions concerning the coupling of these two cellular cycles.

PMID- 14711432
TI  - Centrosomes: Sfi1p and centrin unravel a structural riddle.
AB  - The discovery of Sfi1p as a novel binding partner for the Ca2+-binding protein
      centrin has provided new insight into the dynamic behavior of centrosomes. Sfi1
      binds to multiple centrin molecules along a series of internal repeats, and the
      complex forms Ca2+-sensitive contractile fibers that function to reorient
      centrioles and alter centrosome structure.

PMID- 14711433
TI  - Immune activation: death, danger and dendritic cells.
AB  - Dendritic cells are critical for host immunity, and sense microbes with pathogen
      recognition receptors. New evidence indicates that these cells also sense uric
      acid crystals in dead cells, suggesting that the immune system is conscious not
      only of pathogens, but also of death and danger.

PMID- 14711434
TI  - Vesicle transport: a close collaboration of Rabs and effectors.
AB  - COPII vesicles transport proteins destined for secretion from the ER to the Golgi
      apparatus. A recent study has shown that, in budding yeast, the formation of
      COPII vesicles requires Yip1p, an effector protein of a Rab GTPase.

PMID- 14711435
TI  - Embryonic cleavage cycles: how is a mouse like a fly?
AB  - The evolutionary advent of uterine support of embryonic growth in mammals is
      relatively recent. Nonetheless, striking differences in the earliest steps of
      embryogenesis make it difficult to draw parallels even with other chordates. We
      suggest that use of fertilization as a reference point misaligns the earliest
      stages and masks parallels that are evident when development is aligned at
      conserved stages surrounding gastrulation. In externally deposited eggs from
      representatives of all the major phyla, gastrulation is preceded by specialized
      extremely rapid cleavage cell cycles. Mammals also exhibit remarkably fast cell
      cycles in close association with gastrulation, but instead of beginning
      development with these rapid cycles, the mammalian egg first devotes itself to
      the production of extraembryonic structures. Previous attempts to identify common
      features of cleavage cycles focused on post-fertilization divisions of the
      mammalian egg. We propose that comparison to the rapid peri-gastrulation cycles
      is more appropriate and suggest that these cycles are related by evolutionary
      descent to the early cleavage stages of embryos such as those of frog and fly.
      The deferral of events in mammalian embryogenesis might be due to an evolutionary
      shift in the timing of fertilization.

PMID- 14711437
TI  - Tumors of the conjunctiva and cornea.
AB  - Tumors of the conjunctiva and cornea comprise a large and varied spectrum of
      conditions. These tumors are grouped into two major categories of congenital and
      acquired lesions. The acquired lesions are further subdivided based on origin of
      the mass into surface epithelial, melanocytic, vascular, fibrous, neural,
      histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and
      secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary
      acquired melanosis, melanoma, and other ocular surface conditions like ocular
      melanocytosis and secondary pigmentary deposition. The most frequent
      nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma,
      both of which have typical features appreciated on clinical examination. The
      caruncle displays a slightly different array of tumors compared to those
      elsewhere on the conjunctiva, as nevus and papilloma are most common, but
      oncocytoma and sebaceous gland hyperplasia, adenoma, and carcinoma can be found.
      In this report, we provide clinical description and illustration of the many
      conjunctival and corneal tumors and we discuss tumor management.

PMID- 14711438
TI  - Polypoidal choroidal vasculopathy.
AB  - Polypoidal choroidal vasculopathy was first described as a peculiar hemorrhagic
      disorder of the macula, characterized by recurrent sub-retinal and sub-retinal
      pigment epithelium bleeding in middle aged black women. The use of indocyanine
      green angiography and subsequently of optical coherent tomography has widened our
      ability to study and understand the pathophysiology of this disorder. The primary
      abnormality involves the choroidal circulation, and the characteristic lesion is
      an inner choroidal vascular network of vessels ending in an aneurysmal bulge or
      outward projection, visible clinically as a reddish orange, spheroid, polyp-like
      structure. We have also recognized that individuals of African-American and Asian
      descents are more at risk for developing polypoidal choroidal vasculopathy as the
      disorder seems to preferentially affect pigmented individuals. However, it has
      been shown that while that still holds true, patients of other racial backgrounds
      may be afflicted. Particularly, polypoidal choroidal vasculopathy has been found
      to be present in about 8-13% of white patients with clinical appearance of
      exudative age-related macular degeneration. Polypoidal choroidal vasculopathy has
      also been reported in Irish, French, German, and Italian patients. The natural
      course of the disease often follows a remitting-relapsing course, and clinically,
      it is associated with chronic, multiple, recurrent serosanguineous detachments of
      the retinal pigment epithelium and neurosensory retina with long-term
      preservation of good vision. Photodynamic treatment appears to be a promising
      alternative to conventional laser therapy, for the treatment of polypoidal
      choroidal vasculopathy. In conclusion, polypoidal choroidal vasculopathy seems to
      be a distinct clinical entity that should be differentiated from other types of
      choroidal neovascularization associated with age-related macular degeneration and
      other known choroidal degenerative, inflammatory, and ischemic disorders.

PMID- 14711439
TI  - Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision--a systematic
      review of placebo-controlled trials.
AB  - We have systematically reviewed placebo-controlled trials of V. myrtillus
      extracted anthocyanosides for evidence of positive effects on night vision.
      Searches of computerized databases and citations in retrieved articles identified
      30 trials with outcome measures relevant to vision in reduced light. Of these, 12
      were placebo-controlled. The 4 most recent trials were all randomized controlled
      trials (RCTs) and were negative in outcome. A fifth RCT and 7 non-randomized
      controlled trials reported positive effects on outcome measures relevant to night
      vision. Negative outcome was associated with more rigorous methodology but also
      with lower dose level and extracts from geographically distinct sources that may
      differ in anthocyanoside composition. Healthy subjects with normal or above
      average eyesight were tested in 11 of the 12 trials. The hypothesis that V.
      myrtillus anthocyanosides improves normal night vision is not supported by
      evidence from rigorous clinical studies. There is a complete absence of rigorous
      research into the effects of the extract on subjects suffering impaired night
      vision due to pathological eye conditions. Evidence from methodologically weaker
      trials and auxiliary evidence from animal studies, trials of synthetic
      anthocyanosides, and a recent randomized controlled trial of Ribes nigrum (black
      currant) anthocyanosides may warrant further trials of V. myrtillus
      anthocyanosides in subjects with impaired night vision.

PMID- 14711440
TI  - The amniotic membrane in ophthalmology.
AB  - The amniotic membrane is the innermost of the three layers forming the fetal
      membranes. It was first used in 1910 in skin transplantation. Thereafter it has
      been used in surgical procedures related to the genito-urinary tract, skin,
      brain, and head and neck, among others. The first documented ophthalmological
      application was in the 1940s when it was used in the treatment of ocular burns.
      Following initial reports, its use in ocular surgery abated until recently when
      it was re-discovered in the Soviet Union and South America. Its introduction to
      North America in the early 1990s heralded a massive surge in the ophthalmic
      applications of this membrane. The reintroduction of amniotic membrane in
      ophthalmic surgery holds great promise; however, although it has been shown to be
      a useful and viable alternative for some conditions, it is currently being used
      far in excess of its true useful potential. In many clinical situations it offers
      an alternative to existing management options without any distinct advantage over
      the others. Further studies will undoubtedly reveal the true potential of the
      membrane, its mechanism(s) of action, and the effective use of this tissue in
      ophthalmology.

PMID- 14711441
TI  - Ocular tuberculosis masquerading as ocular tumors.
AB  - Tuberculosis has re-emerged as a serious public health problem in recent years.
      The ocular manifestations of tuberculosis are uncommon and diverse. Occasionally,
      patients initially present with ocular symptoms that simulate intraocular
      malignancy or other inflammatory conditions. We present five patients with ocular
      tuberculosis who were referred with the suspicion of ocular malignancy. Four of
      the five patients had recently emigrated to the United States. The presenting
      features of these patients were panophthalmitis (one patient), endophthalmitis
      leading to scleral perforation (one patient), active choroidal granuloma
      associated with uveitis (two patients), and amelanotic choroidal lesion without
      inflammatory signs (one patient). Of these five cases, two had a known history of
      systemic tuberculosis, while the ocular findings in the other three cases were
      the presenting manifestation of systemic tuberculosis. Multi-drug antituberculous
      regimen were employed in all cases for a mean of 9 months (median 6 months, range
      6-12 months). Three patients responded well to therapy with salvage of the globe
      and the two remaining patients underwent primary enucleation for blind painful
      eye or perforated eye. In conclusion, ocular tuberculosis can have variable
      clinical manifestations and occasionally appears as an intraocular or epibulbar
      tumor. A high degree of clinical suspicion is important, especially in immigrants
      from developing countries.

PMID- 14711442
TI  - Sprint car visual loss.
AB  - A 16-year-old boy developed bilateral visual loss 24 hours after a sprint car
      accident. Bilateral central scotomas were demonstrated but were unexplained by a
      thorough eye examination and neuro-imaging. A diagnosis of commotio retinae was
      established by multi-focal ERG testing. This relatively new technique is
      discussed, including comparison to full-field ERG and clinical applications.

PMID- 14711443
TI  - Subretinal fluid in primary rhegmatogenous retinal detachment: physiopathology
      and composition.
AB  - During retinal detachment, subretinal fluid is present, whose composition and
      physiopathology are still little known. Under normal conditions, osmotic and
      oncotic pressures help keep the retina in place, but the main retinal attachment
      force is provided by active transport in the pigment epithelium. Subretinal fluid
      composition varies according to detachment duration; total protein concentration
      in subretinal fluid increases with time. In addition, all proteins are
      qualitatively modified. The detached retina loses its oxygen supply, and it then
      uses the anaerobic pathway to degrade glucose. Thus, long-duration retinal
      detachments feature increased lactic acid and dextrose concentrations.
      Phospholipids are also increased in subretinal fluid, reflecting retinal
      degradation. This review presents data on the physiopathology and composition of
      the subretinal fluid in retinal detachments.

PMID- 14711444
TI  - Practical astigmatism analysis for refractive outcomes in cataract and refractive
      surgery.
AB  - The fundamental concepts underpinning the vectorial analysis of astigmatism are
      straightforward and intuitive, easily understood by employing a simple golf
      putting analogy. The Alpins methodology utilizes three principal vectors and the
      various ratios between them to provide an aggregate analysis for astigmatic
      change with parallel indices for spherical correction. A comparative analysis
      employing both arithmetic and vectorial means together with necessary nomogram
      adjustments for refining both spherical and astigmatic treatments can also be
      derived. These advanced techniques, together with their suitability for
      statistical analysis, comprehensively address the outcome analysis requirements
      of the entire cornea and the eye's refractive correction, for the purpose of
      examining success in cataract and refractive surgery.

PMID- 14711450
TI  - Central serous chorioretinopathy and glucocorticoids.

PMID- 14711452
TI  - The treatment of pterygium.

PMID- 14711454
TI  - Cyanidins: metabolism and biological properties.
AB  - Cyanidin and its glycosides belong to the anthocyanins, a widespread class of
      water-soluble plant compounds that are responsible for the brilliant color (red,
      orange, blue) of fruits and flowers. They are widely ingested by humans as it has
      been estimated a daily intake around 180 mg, mainly deriving from fruits and red
      wines. This paper reviews the literature on the biological activities, absorption
      and metabolism of cyanidins, with emphasis to the antioxidant, antimutagenic and
      other protective activities ascribed to these compounds. Their role in
      contrasting development of cancer and other pathologies is also reviewed. It is
      concluded that a great deal of work is still necessary to i) definitively clarify
      the metabolism of cyanidins in human beings; ii) assess the dietary burden and
      variations within and between populations; iii) evaluate the relationship between
      cyanidin glycosides-rich food consumption and incidence of given pathologies. The
      amount of work to be performed is even more significant when considering a
      possible therapeutic use of cyanidin glycosides-based drugs. With this aim,
      information on absorption, distribution, metabolism and excretion of cyanidin
      glycosides administered by main possible routes are largely insufficient.
      However, consisting findings allow looking at cyanidins as dietary compounds with
      a potential beneficial role for human health.

PMID- 14711455
TI  - Differential effect of lentil feeding on proteosynthesis rates in the large
      intestine, liver and muscle of rats.
AB  - The aim of this work was to test the hypothesis that the trophic effect of lentil
      feeding on large intestine results from a stimulation of protein synthesis and to
      determine whether it interferes with protein metabolism in other splanchnic or
      peripheral organs. Two groups of growing Sprague Dawley male rats were pair-fed
      iso-caloric iso-nitrogenous balanced diets containing either cooked lentils (Lens
      esculenta puyensis) or casein as unique protein source. Protein synthesis rates
      were measured in vivo, in large intestine, liver and gastrocnemius at the
      postprandial state. In large intestine, protein and ribonucleic acid contents
      were higher in the lentil-fed group than in the control group, and the amount of
      proteins synthesized was also higher (+57%). By contrast, liver protein and
      ribonucleic acid contents as well as protein synthesis rates were significantly
      lower in the lentil-fed group than in the control group. In the gastrocnemius
      muscle protein and ribonucleic acid contents were significantly lower and the
      amount of protein synthesized was also lower (-18%) in the lentil fed group than
      in the control group. This study suggests that stimulation of protein synthesis
      in the large intestine is compensated for by a decrease in liver and muscle.

PMID- 14711456
TI  - Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead
      induced lipid peroxidation in rat liver.
AB  - Oxidative stress with subsequent lipid peroxidation has been postulated as one
      mechanism for lead toxicity. Hence in assessing the protective effects of lipoic
      acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead toxicity, they were
      tested either separately or in combination for their effects on selected indices
      of hepatic oxidative stress. Elevated levels of lipid peroxides were accompanied
      by altered antioxidant defense systems. Lead acetate (Pb - 0.2%) was administered
      in drinking water for five weeks to induce toxicity. LA (25 mg kg(-1) body wt.
      day(-1) i.p) and DMSA (20 mg kg(-1) body wt. day(-1) i.p) were administered
      individually and also in combination during the sixth week. Lead damage to the
      liver was evident in the decreases in hepatic enzymes alanine transaminase (
      38%), aspartate transaminase (-42%) and alkaline phosphatase (-43%); increases in
      lipid peroxidation (+38%); decreases in the antioxidant enzymes catalase (-45%),
      superoxide dismutase (-40%), glutathione peroxidase (-46%) and decreases in
      glutathione (-43%) and decreases in glutathione metabolizing enzymes, glutathione
      reductase (-59%), glucose-6-phosphate dehydrogenase (-27%) and glutathione-S
      transferase (-42%). In combination LA and DMSA completely ameliorated the lead
      induced oxidative damage. Either compound alone was however only partially
      protective against lead damage.

PMID- 14711457
TI  - Decreased serum leptin and muscle oxidative enzyme activity with a dietary loss
      of intra-abdominal fat in rats.
AB  - The purpose of the present study was to investigate the relationship among intra
      abdominal adipose storage, adaptation in the serum leptin concentration and
      skeletal muscle enzyme activity after a 4-week energy restriction (ER). Thirty
      one male Wistar rats were divided into 40% energy restricted (n=24) or ad libitum
      fed control (CL) rats (n=7). The energy-restricted rats were grouped into the
      most fat (MF, n=7), medium (n 10) and the least fat (LF, n=7) by their intra
      abdominal fat pads mass (epididymal, mesenteric, and perirenal) after ER. A
      superficial portion of M. gastrocnemius tissue obtained before and after the diet
      period were analyzed to determine the activities of hexokinase (HK), beta
      hydroxyacyl CoA dehydrogenase (beta-HAD) and citrate synthase (CS). Blood samples
      were also collected for a serum leptin assay. At the baseline, no difference was
      found in either the leptin concentration or the enzyme activities among LF, MF
      and CL. The serum leptin concentration was positively correlated with the muscle
      activities of beta-HAD and CS, while it negatively correlated with HK/beta-HAD.
      After ER, the activities of HK, beta-HAD and CS were all significantly lower in
      LF than in CL. Among the energy-restricted rats, the intra-abdominal fat pad
      weight, leptin concentration and the activities of beta-HAD, CS, beta-HAD/CS all
      significantly correlated with one another. The changes in leptin and the activity
      of beta-HAD were also positively correlated. These findings indicate that
      parallel decreases in the serum leptin and skeletal muscle enzyme activities with
      the energy restriction-induced intra-abdominal adipose reduction, thus may
      suggest the leptin to have a regulative effect on the muscle enzyme activity
      during ER.

PMID- 14711458
TI  - Garlic supplementation increases peripheral blood flow: a role for interleukin-6?
AB  - There is considerable epidemiological and clinical evidence that regular garlic
      supplementation reduces cardiovascular risk. In this study, we have investigated
      the hypothesis that dietary garlic supplementation increases tissue blood flow
      and this is mediated by the vasodilatory actions of interleukin-6 (IL-6). Venous
      occlusion plethysmography was used to measure resting calf blood flow before and
      after oral administration of 600 mg of garlic tablets once daily for 7 days in 13
      young healthy female volunteers (treatment group) and 13 female controls matched
      for age and body mass index (BMI). Blood samples were obtained at the time of
      plethysmography to measure plasma levels of IL-6, nitrate, nitrite and c-GMP. In
      the treatment group, calf blood flow increased significantly from 3.01 (2.56 to
      3.3) ml min(-1) 100 mL(-1) of tissue before garlic to 3.46 (3.0 to 4.03) ml min(
      1) 100 mL(-1) of tissue after 7 days of garlic (P = 0.001). Plasma IL-6
      concentrations increased significantly from 54.6 (32.3 to 151.6) mcg/mL before to
      151 (135.75 to 422.3) mcg/mL after 7 days of garlic (P = 0.02). However, there
      was no significant change in the plasma levels of nitrate, nitrite and c-GMP
      after the garlic (P = 0.4, 0.9 and 0.65 respectively). In the control group,
      resting calf blood flow and plasma levels of IL-6, nitrite, nitrate and c-GMP
      remained unchanged after 7 days (P = 0.62, 0.92, 0.28 and 0.35 respectively).
      Calf blood flow showed a non-linear correlation with plasma IL-6 levels after
      garlic supplementation (r = 0.86, p = <0.001) but not before. There was no
      significant relationship between blood flow and plasma nitrate, nitrite and c-GMP
      in either groups and between blood flow and IL-6 in the control group. These data
      suggest that garlic supplementation increases resting tissue blood flow and this
      may be mediated by IL-6.

PMID- 14711459
TI  - Chicken extract affects colostrum protein compositions in lactating women.
AB  - This study investigated the effect of supplementation with chicken extract on
      plasma and colostrum protein compositions in lactating women. Thirty healthy
      pregnant women were evenly divided into the control (n = 15) or chicken extract
      (CE) group (n = 15). The CE group was given one bottle (70 mL/bottle) of chicken
      extract three times a day to provide 18 g protein from the 37th week pregnancy to
      3 days postpartum. All women in the CE group consumed chicken extract at least
      for 2 weeks (18 +/- 5 days). High protein supplement was restricted in the
      control group. Blood samples were collected during the 37th week pregnancy and 3
      day postpartum, and milk was collected during 3-day postpartum. The results
      showed that plasma total protein was significantly lower by 14% in the CE group
      compared with that in the control group during 3-day postpartum. Plasma epidermal
      growth factor (EGF) significantly elevated by 236% during 3-day postpartum
      compared with those during the 37th week pregnancy in the CE group. The levels of
      lactoferrin, EGF, and transforming growth factor-beta2 (TGF-beta2) in colostrum
      significantly increased by 34%, 62%, and 196%, respectively, in the CE group
      compared with those in the control group. However, the levels of total protein,
      casein, lactalbumin, and secretory immunoglobulin A in colostrum did not
      significantly differ between two groups. Therefore, supplementation with chicken
      extract increased colostrum levels of lactoferrin, EGF, and TGF-beta2, which are
      important for the growth and immune functions of the infants, in lactating women.

PMID- 14711460
TI  - In vitro immune response of human peripheral blood cells to vitamins C and E.
AB  - Since oxygen free radicals exert a noxious effect on cell functions, the purpose
      of the study was to examine the influence of the antioxidant vitamins C and E on
      the phagocytic capacity, apoptotic death, production of TNFalpha and IL-10 by
      human peripheral blood cells. In addition, an attempt to find a correlation
      between the effect of these vitamins on apoptosis and DNA synthesis was carried
      out. Peripheral white blood cells obtained from 27 healthy volunteers were
      incubated for 24 hr without and with vitamins C and E at doses extrapolated from
      clinical practice. Incubation of cells with vit. C caused a significant increase
      in the number of latex particles internalized by each individual
      polymorphonuclear cell, but not by monocytes. Both vitamins did not change the
      number of cells capable for phagocytosis. By the method of propidium iodide
      staining for detection of apoptosis, incubation of the cells with 0.2 mg/mL vit.
      C for 24 hrs caused a 39% increase in the percentage of apoptotic cells, as
      compared to those kept at the same incubation conditions without vitamin. 0.125
      mg/mL of vit. E did not affect the percentage of apoptotic cells. On the other
      hand, applying the caspase-3 method for apoptosis detection, vitamins C and E did
      not affect the caspase-3 activity. Both vitamins caused an inhibition of 3H-TdR
      incorporation, which was dose-dependent for vit. C. Concentrations of the
      vitamins lower than those mentioned above did not alter DNA synthesis. While
      TNFalpha production was not affected by both vitamins, the spontaneous secretion
      of IL-10 was dose-dependently reduced by vit. C but remained unaltered following
      incubation with vit. E. The results, although observed in vitro, might be of
      importance when those vitamins are administered to healthy subjects.

PMID- 14711461
TI  - Effects of dietary alpha linolenic acid on cholesterol metabolism in male and
      female hamsters of the LPN strain.
AB  - N-3 polyunsaturated fatty acids and estrogens are recognized as protective
      factors of atherosclerosis, however their interactions on cholesterol metabolism
      remain unclear. Male and female hamsters were fed for 9 weeks diets containing
      12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or
      saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited
      lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (
      17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol
      ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content
      was 2.7-fold lower in response to the "linseed" diet, whereas the concentration
      of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol
      7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By
      contrast, the LDL receptor concentration did not vary with the diet. Females
      exhibited higher concentration of LDL (+24%), lower concentration of plasma
      triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of
      biliary phospholipids (-19%). Besides, there was also an interaction between
      gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL
      concentration, were 2 to 4 fold higher than in the other groups. These data
      suggest that gene and/or metabolic regulations by fatty acids could interact with
      that of sex hormones and explain why males are more sensitive to dietary fatty
      acids.

PMID- 14711462
TI  - Pain management in cancer patients with bone metastases remains a challenge.

PMID- 14711463
TI  - The elderly, fragile tumor patient: radiotherapy as an effective and most
      feasible treatment modality.

PMID- 14711464
TI  - Symptom burden in the last week of life.
AB  - In order to investigate symptom burden in the last week of life, we conducted
      after-death interviews with close relatives of deceased older persons from a
      population-based sample of older people in The Netherlands (n=270). Results show
      that fatigue, pain, and shortness of breath were common (83%, 48% and 50%,
      respectively). Other symptoms were confusion (36%), anxiety (31%), depression
      (28%), and nausea and/or vomiting (25%). Cancer patients and patients with
      chronic obstructive pulmonary disease were clearly at a disadvantage with respect
      to pain and shortness of breath, respectively. Furthermore, cognitive decline
      turned out to be predictive of specific symptom burden. Persons with cognitive
      decline in the last three months had a higher symptom burden and different
      symptoms compared to patients with no cognitive decline. It is suggested that
      older persons with cognitive decline require specific attention.

PMID- 14711465
TI  - Further validation of the multidimensional fatigue symptom inventory-short form.
AB  - A growing body of evidence is documenting the multidimensional nature of cancer
      related fatigue. Although several multidimensional measures of fatigue have been
      developed, further validation of these scales is needed. To this end, the current
      study sought to evaluate the factorial and construct validity of the 30-item
      Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). A heterogeneous
      sample of 304 cancer patients (mean age 55 years) completed the MFSI-SF, along
      with several other measures of psychosocial functioning including the MOS-SF-36
      and Fatigue Symptom Inventory, following the fourth cycle of chemotherapy
      treatment. The results of a confirmatory factor analysis indicated the 5-factor
      model provided a good fit to the data as evidenced by commonly used goodness of
      fit indices (CFI 0.90 and IFI 0.90). Additional evidence for the validity of the
      MFSI-SF was provided via correlations with other relevant instruments (range 
      0.21 to 0.82). In sum, the current study provides support for the MFSI-SF as a
      valuable tool for the multidimensional assessment of cancer-related fatigue.

PMID- 14711466
TI  - The symptom monitor. A diary for monitoring physical symptoms for cancer patients
      in palliative care: feasibility, reliability and compliance.
AB  - The aim of this study was to evaluate the feasibility, reliability and compliance
      of a new instrument, a diary to monitor physical symptoms for patients with
      cancer in the palliative phase of their illness. The development of the diary
      took place in three phases: two pilot studies and one intervention study. In
      Pilot I, reliability was tested within 13 pairs of patients and their proxy in a
      patient-proxy comparison. Pilot II was performed to test the feasibility of the
      instrument among 47 frail elderly. In the intervention study among patients with
      cancer in the palliative phase, the feasibility as well as the compliance has
      been tested. The phases have been completed with good results: reliability (ICC)
      of prevalent symptoms was above 0.75, good feasibility and good compliance. The
      Symptom Monitor can be used by patients and doctors as an instrument to monitor
      physical symptoms. The effectiveness of the use of this diary for improvement in
      treatment of symptoms in the palliative phase of cancer is being tested in a
      randomized clinical trial.

PMID- 14711467
TI  - Cancer patients' share in a population's use of opioids. A linkage study between
      a prescription database and the Danish Cancer Registry.
AB  - The aim of this study was to 1) assess cancer patients' share in a population's
      use of opioids and how much it influences the total use, and 2) analyze trends in
      the population's use of "weak" and "strong" opioids during a five-year period.
      Person-identifiable data on opioid prescriptions and cancer diagnoses from a
      Danish county (n approximately 470,000) were retrieved from a prescription
      database, OPED, and The Danish Cancer Registry from 1993-1997 (identifying 23,843
      cancer patients). In a given year, 14% of the population's opioid users were
      cancer patients, and they received 23% of the total opioid consumption. Over
      time, the number of patients using weak opioids increased and the number using
      strong opioids decreased among both cancer patients and non-cancer patients.
      Cancer patients' consumption of strong opioids increased dramatically in 1996
      1997, almost accounting for the entire increase in the whole population's
      consumption of strong opioids.

PMID- 14711468
TI  - Desire for death and requests to hasten death of Japanese terminally ill cancer
      patients receiving specialized inpatient palliative care.
AB  - A desire for death and requests to hasten death are major topics in recent
      medical literature. The aim of this study was to clarify the bereaved family
      reported incidence and reasons for desiring death and requests to hasten death
      during the whole course of terminally ill cancer patients receiving specialized
      palliative care in Japan. A nationwide questionnaire survey of 500 primary
      caregivers yielded a total of 290 responses (effective response rate, 62%). Sixty
      two (21%) families reported that the patients had expressed a desire to die, and
      29 (10%) families reported that the patients had requested that death be
      hastened. The major reasons for desiring death and requests to hasten death were:
      burden on others, dependency, meaninglessness, unable to pursue pleasurable
      activities, general malaise, pain, dyspnea, concerns about future distress, and
      wish to control the time of death. No intolerable physical symptoms were reported
      in 32% and 28% of the patients who desired death and those who requested to
      hasten death, respectively. Concerns about future distress and wishes to control
      the time of death were significantly more likely to be listed as major reasons
      for desiring death in patients who requested that death be hastened than those
      who did not. A desire for death and requests to hasten death are not uncommon in
      terminally ill cancer patients receiving specialized inpatient palliative care in
      Japan. More intensive strategies for general malaise, pain, and dyspnea near the
      end of life, and for feelings of being a burden, meaninglessness, and concerns
      about future distress would alleviate the serious suffering of patients with a
      desire for death. However, some patients with a strong wish to control the time
      of death might not receive benefit from conventional palliative care.

PMID- 14711469
TI  - Palliative care consultation in The Netherlands: a nationwide evaluation study.
AB  - Palliative care in The Netherlands is mainly provided by generalist professionals
      who are part of the regular health care system. In order to provide good quality
      palliative care, they need options for training and consultation. Therefore,
      Palliative Care Consultation (PCC) teams were established, which inform, support,
      and advise professional caregivers involved with patients in palliative care
      without taking over responsibility. This study is the first nationwide study on
      PCC teams. Investigated was the nature and effect of consultations by
      registration and evaluation of consultations given by 19 PCC teams during a one
      year period. Sixty-one percent of the requesting caregivers were primary care
      professionals and the problems discussed covered the entire field of palliative
      care, although physical problems played a dominant role. Although the patient was
      often not seen by the consultant, the consultant appeared to be able to identify
      more problems than initially discussed by the requesting professional. The types
      of problems discussed were hardly related to patient characteristics but more
      related to the discipline of the professional caregiver. According to the
      requesting professionals, consultation was helpful and contributed to improving
      the quality of palliative care.

PMID- 14711470
TI  - Effects of a continuing education program on nurses' practices of cancer pain
      assessment and their acceptance of patients' pain reports.
AB  - A hospital-based quasi-experimental (pretest and post-test) study was conducted
      in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a
      continuing education program (CEP) on nurses' practices of cancer pain assessment
      and their acceptance of patients' pain reports with respect to four types of
      misconceptions. A questionnaire was sent to on-duty nurses or head nurses with
      patient care responsibilities before the implementation of CEP (n=645) and six
      months after the program (n=630). The response rates were 92.6% and 91.3% for
      pretest and post-test surveys, respectively. The CEP was implemented in 8 weeks
      with four-repeated sessions of 4-hour lectures. A one-day workshop focused on
      cancer pain assessment and treatment was held 3 months after the four-repeated
      sessions. Several educational strategies and teaching materials were used in the
      CEP. The results showed that CEP made statistically significant yet moderate
      improvement in nurses' practices of pain assessment using pain rating scales
      (pretest 3.29+/-0.76 vs. post-test 3.48+/-0.75, P<0.001) and acceptance of
      patient's pain reports without misconceptions on addiction (3.12+/-0.80 vs.
      3.39+/-0.90, P<0.001), phantom pain (3.91+/-0.96 vs. 4.07+/-0.92, P=0.005), and
      placebo testing (3.63+/-0.72 vs. 3.81+/-0.73, P<0.001), except on patient gender
      age-related doubts (3.60+/-0.72 vs. 3.67+/-0.77, P=0.109). In order to achieve
      further improvement, additional follow-up CEP combined with a hospital-wide
      institutionalization of pain assessment should be promoted and implemented in the
      future.

PMID- 14711471
TI  - Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case
      report.
AB  - We present two patients with chemotherapy-induced painful neuropathy that had
      been poorly controlled with medications but successfully treated with spinal cord
      stimulation (SCS). A trial period of SCS provided effective pain relief in both
      patients who subsequently underwent permanent stimulator implantation.
      Psychophysical tests were performed before and after the implantation of trial
      and permanent stimulators. SCS improved pain scores and facilitated a reduction
      of medications. Both patients reported improved gait and one of them also
      reported an increase in leg flexibility. Psychophysical tests demonstrated an
      improvement in touch and sharpness detection thresholds. In summary, SCS offers a
      therapeutic option for patients with chemotherapy-induced peripheral neuropathy
      who have poor pain relief with standard medical treatment.

PMID- 14711472
TI  - Punctate midline myelotomy for intractable visceral pain caused by hepatobiliary
      or pancreatic cancer.
AB  - The purpose of this study was to demonstrate the existence of a newly recognized
      midline posterior column pathway that mediates the perception of visceral pain
      resulting from hepatobiliary or pancreatic cancer. A punctate midline myelotomy
      (PMM) of T(3) level was performed in 6 patients who experienced severe visceral
      pain caused by hepatobiliary or pancreatic cancer. Preoperatively, the pain was
      refractory to strong opioids. Clinical efficacy of PMM was evaluated by comparing
      patient pain rating on a visual analogue scale. Follow-up periods ranged from 2
      18 weeks after operation. All 6 patients had immediate pain relief after
      operation. Although the pain recurred from 2-12 weeks later in 3 patients, the
      severity of recurrent cancer pain markedly decreased. No adverse neurological
      sequelae were observed. Our results of high thoracic PMM offer clinical support
      for the concept that neurosurgical interruption of midline visceral pain pathway
      can effectively control severe visceral pain without causing adverse neurological
      sequelae in patients with hepatobiliary or pancreatic cancer.

PMID- 14711473
TI  - Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic
      syndromes in patients with advanced lung adenocarcinoma: a pilot study.
AB  - Systemic syndromes characterized by a persistent activity of circulating
      mediators (cytokines) are frequently present with advanced cancer. We grouped
      under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a
      particular variety of distressing systemic syndrome characterized by
      dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping
      clinical manifestations. SIMS may include cachexia, anorexia, nausea, early
      satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of
      this study was to ameliorate some of the SIMS symptoms in a homogeneous group of
      lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with
      evidence of SIMS were studied. SIMS was defined as the presence of weight loss,
      anorexia, fatigue performance status>/=2 and acute-phase protein response.
      Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200
      mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13
      patients either had stable weight (+/- 1%) or had gained weight. There were
      significant differences in improvement of body-weight-change rate, nausea, early
      satiety, fatigue, appetite and performance status. Patients who had any kind of
      lung infection showed higher levels of IL-10 compared to non-infected patients
      (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma,
      treated with MPA, celecoxib and dietary intervention, might have considerable
      improvement in certain SIMS outcomes. This multitargeted symptomatic approach
      deserves further study.

PMID- 14711474
TI  - Laribacter hongkongensis: a potential cause of infectious diarrhea.
AB  - In this study, we describe the isolation of Laribacter hongkongensis, a recently
      described genus and species of bacterium, in pure culture on charcoal
      cefoperazone deoxycholate agar from the stool of six patients with diarrhea.
      Three patients were residents of Hong Kong, and three of Switzerland. In none of
      the stool samples obtained from these six patients was Salmonella, Shigella,
      enterohemorrhagic Escherichia coli, Vibrio, Aeromonas, Plesiomonas, or
      Campylobacter recovered. Rotavirus antigen detection, electron microscopic
      examination for viruses, and microscopic examinations for ova and cysts were all
      negative for the stool samples obtained from the three patients in Hong Kong.
      Enterotoxigenic E. coli was recovered from one of the patients in Hong Kong.
      Unlike L. hongkongensis type strain HKU1, all the six strains were motile with
      bipolar flagellae. Sequencing of the 16S ribosomal RNA genes of the six strains
      showed that they all had sequences with only 0-2 base differences to that of the
      type strain. Pulsed field gel electrophoresis of the SpeI digested genomic DNA of
      the six isolates and that of the type strain revealed that the seven isolates
      were genotypically unrelated strains. More extensive epidemiologic studies should
      be carried out to ascertain the causative association between L. hongkongensis
      and diarrhea and to define the reservoir and modes of transmission of L.
      hongkongensis.

PMID- 14711475
TI  - Laboratory diagnosis of enteroviral infections of the central nervous system by
      using a nested RT-polymerase chain reaction (PCR) assay.
AB  - Enteroviruses are the most common pathogens identified in infants hospitalized
      for suspected aseptic meningitis. Rapid detection of enterovirus infection is
      essential in taking the decision for treatment with antiviral agents and applying
      infection control measures in hospitalized pediatric patients. The purpose of
      this study was to compare the results of conventional virus isolation with those
      of enteroviral RNA detection by reverse transcription (RT)-PCR method in
      identical specimens from cases of suspected aseptic meningitis. Cerebrospinal
      fluid (CSF) samples were collected for viral examination from 68 pediatric
      patients with suspected aseptic meningitis from 1999 to 2002. These samples were
      inoculated in HeLa, Hep-2 and RD cell culture. The viral RNA was investigated by
      in-house RT-PCR method. The isolated viruses were typed by neutralization test.
      36 of the 68 specimens were detected to be enterovirus positive by culture
      method, while 43 of them yielded positive results when RT-PCR method is used.
      Discrepancies occurred between the two methods in 15 specimens. While 11
      specimens were positive by RT-PCR, these are found to be culture-negative. The
      isolated viruses were typed as Echovirus 30 (n: 30), Group B coxsackievirus (n:
      5) and one isolate could not be typed by neutralization. Because of higher
      sensitivity and rapidity of RT-PCR, it is superior (p = 0.016) to virus culture
      of CSF for the diagnosis of enterovirus meningitis. Although the clinical
      usefulness of viral culture from CSF is limited, the final laboratory
      identification needs cultural techniques.

PMID- 14711476
TI  - Whole blood samples as an alternative to serum for detection of immunity to
      measles virus by ELISA.
AB  - The aim of this study was to evaluate enzyme linked immunosorbent assay (ELISA)
      as a testing strategy for detection of antibodies against measles virus from
      microquantities of blood soaked onto filter paper. We studied 165 healthy
      children in the age group of 1 to 2 years, attending the outpatient department of
      pediatrics. Two sets of samples were collected from each child. One by
      venipuncture and the other on Whatman filter paper-3 discs of 20 mm size by
      finger or heel prick so that each strip is completely soaked with blood on both
      sides. These were tested for measles virus antibodies by ELISA using Melotest
      measles IgG commercial ELISA kit manufactured by Melotec S. A. (Barcelona,
      Spain). The resulting sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) of the filter paper (FP) ELISA compared to
      serum ELISA was 100, 90, 97.8, and 100%, respectively. The correlation
      coefficient r = 0.93% (p < 0.001) and the agreement between the two techniques
      was 98% as calculated by the Kappa statistical method. The present study has
      found filter paper testing by ELISA to be a promising qualitative technique for
      detection of immunity against measles.

PMID- 14711477
TI  - Diagnosing and monitoring of invasive aspergillosis during antifungal therapy by
      polymerase chain reaction: an experimental study in mice.
AB  - This study evaluated the value of polymerase chain reaction (PCR) for diagnosing
      and monitoring of invasive aspergillosis during amphotericin B therapy. PCR,
      microscopy and culture of tissues samples (n = 126) and blood samples (n = 78) of
      experimentally infected mice (n = 42) were performed. The PCR results of treated
      were compared to those of untreated animals; Aspergillus fumigatus and A. terreus
      were used in this study. In the amphotericin B treated group the sensitivities of
      PCR, microscopic examination and culture of the various tissues were 69, 58, and
      53%, respectively; the specificities of all examinations were 100%. In the
      untreated group the sensitivities of PCR, microscopic examination, and culture
      were 72, 64, and 57%, respectively; the specificities of all examinations were
      100%. The 78 blood samples taken from mice under therapy were tested by PCR over
      a period of 8 days following Aspergillus infection. The test sensitivity was 77%,
      the specificity 46%, the positive predictive value 59%, and the negative
      predictive value 67%. In the untreated group the sensitivity was 92%, the
      specificity 46%, the positive predictive value 63%, and the negative predictive
      value 86%. The results suggest that this PCR method has possible clinical value
      for improving the diagnosis of invasive Aspergillus infection. Monitoring of
      blood under antifungal therapy is not recommended.

PMID- 14711478
TI  - Evaluation of the BDProbeTec ET system as screening tool in the direct detection
      of mycobacterium tuberculosis complex in respiratory specimens.
AB  - We evaluated the BDProbeTec ET System (Becton Dickinson) for the routine
      detection of Mycobacterium tuberculosis complex (MTC) in respiratory specimens
      and pleural fluids, comparing with microscopy (Ziehl Neelsen stain, ZN) and
      culture in liquid (BACTEC MGIT 960, MGIT) and solid (Lowenstein Jensen, LJ)
      media. Five hundred and two specimens, collected from 266 patients, of which 257
      with suspected tuberculosis and 9 receiving anti-tuberculosis treatment, were
      investigated. Thirty-nine specimens were positive by any method, including false
      positives. Mycobacteria were isolated from 33 specimens (32 Mycobacterium
      tuberculosis and 1 Mycobacterium chelonae). Thirty-six specimens were BDProbeTec
      ET positive, 33 specimens were MGIT positive, 27 were LJ positive and 22 were ZN
      positive. With BDProbeTec ET, 2 specimens were false negative (culture positive),
      and 2 specimens from non-treated patients were false positive (culture negative).
      The overall sensitivity, specificity, and positive and negative predictive values
      for BDProbeTec ET compared to culture were 93.7, 98.7, 83.3, and 99.5%,
      respectively, while with smear-positive and smear-negative specimens the
      sensitivities were 100% and 81.5% respectively. In five treated patients the
      disappearance of MTC could be monitored using BDProbeTec ET in parallel with
      culture. The overall inhibition rate was 0.2%. BDProbeTec ET can be very useful
      for rapid detection of MTC, especially in smear-negative respiratory specimens.

PMID- 14711479
TI  - The activity of levofloxacin and other antimicrobials against clinical isolates
      of Streptococcus pneumoniae collected worldwide during 1999-2002.
AB  - Streptococcus pneumoniae is the most important causative bacterial pathogen in
      respiratory infections. Globally, increasing levels of resistant strains
      highlight the need for continued surveillance programs to guide antibiotic
      choice. The current study compared susceptibility results of 4,788 strains of S.
      pneumoniae collected during 2001-2002 to susceptibility results from 3,884
      strains collected from the same hospitals during 1999-2000. Participant centers
      were dispersed throughout five regions. By region, the prevalence of penicillin
      resistant S. pneumoniae and percentage change from the previous 1999-2000 study
      was Mexico (26.0%, 12.5%), Brazil (7.9%; 5.5%), Asia (China, Hong Kong, South
      Korea, Thailand) (44.1%; 0.8%), Europe (France, Germany, Italy, Spain, UK)
      (11.1%; -0.6%) and South Africa (7.9; -1.8%). Multidrug-resistant (MDR) strains
      of S. pneumoniae were most frequently isolated from Asia (36.3%) compared with
      approximately 5% in the other four regions. Increases in the incidence of MDR
      isolates in Mexico (13.5%), Brazil (1.7%) and Asia (6.1%) were reported with no
      increases in MDR in South Africa and Europe. Levofloxacin resistance was rarely
      associated with MDR phenotypes. Levofloxacin maintained an MIC(90) of 1 microg/ml
      against the isolates collected from all five regions with no change during the
      study periods, despite differences in levofloxacin resistance rates between
      regions or nations (0%-3.2%). The prevalence of levofloxacin resistance (MIC > or
      =8 microg/ml) increased only slightly over the study period in Europe (0.3%-0.7%)
      and in Asia (3.0-3.2%), but little or no change was seen in Mexico (3.8%-0%) or
      Brazil or South Africa, where no levofloxacin resistant isolates were detected in
      either study period.

PMID- 14711481
TI  - Increasing prevalence of antimicrobial resistance among Enterobacteriaceae
      uropathogens in Dakar, Senegal: a multicenter study.
AB  - To assess antibiotic susceptibility among Enterobacteriaceae isolated in urine
      from outpatients in Dakar, Senegal, a prospective multicenter study involving 3
      laboratories had been conducted between June and October 2001. During this
      period, 300 strains were isolated and susceptibility testing was performed
      against antibiotics commonly used in treatment of community-acquired urinary
      tract infections (UTI). E. coli and K. pneumoniae represented 89% of isolates.
      The overall resistance rates of ampicillin, amoxicillin-clavulanic acid,
      nalidixic acid, fluoroquinolones and cotrimoxazole were respectively 77.3%,
      34.7%, 14.7%, 13.3%, and 55%. In the light of these results, a re-evaluation of
      first line therapies and prudent use of fluoroquinolones is advised. At the same
      time a continued surveillance of antimicrobial resistance should be developed in
      Senegal in order to control the emergence of multidrug resistant strains and to
      establish a national therapeutic guideline for treatment of UTI.

PMID- 14711480
TI  - In vitro pharmacodynamic activity of gatifloxacin, gemifloxacin, moxifloxacin and
      levofloxacin against Streptococcus pneumoniae containing specific mutations in
      DNA gyrase and topoisomerase IV.
AB  - An in vitro pharmacodynatnic modeling apparatus (PDMA) generated specific
      bacterial kill profiles for single-dose regimens of gatifloxacin (GT),
      gemifloxacin (GM), moxifloxacin (MX) and levofloxacin (LV) against isolates of
      Streptococcus pneumoniae with specific QRDR profiles: SP-WT (no modifications);
      SP-C (changes in parC); and SP-AC (changes in both parC and gyrA). No differences
      in 3-log reduction time or total log reduction were observed among the four
      agents for SP-WT; however, LV failed to achieve a 3-log reduction in SP-C and SP
      AC, and total log reduction after 12 hrs was minimal compared to the other
      agents. GM and MX required less time for 3-log reduction of SP-AC compared to GT,
      but total log reductions in SP-AC were similar among the three newer quinolone
      agents (GM > MX > GT). The study isolates with QRDR modifications greatly reduced
      LV activity. GM and MX maintained the greatest degree of activity against all
      study isolates and their activity was not adversely influenced by the genetic
      modifications in SP-C and SP-AC. The dual targeting characteristic of GM was also
      assessed, but did not offer significant advantages relative to MX and GT.

PMID- 14711482
TI  - Antimicrobial susceptibility trends in Campylobacter jejuni and Campylobacter
      coli isolated from a rural Egyptian pediatric population with diarrhea.
AB  - Comparative and trend analysis was conducted on annual prevalence of
      antimicrobial susceptibility among Campylobacter jejuni and Campylobacter coli
      recovered from rural Egyptian children from 1995 through 2000. C. jejuni and C.
      coli demonstrated significant decreasing trends in ciprofloxacin susceptibility
      over the study period (p < 0.001 for both). In general, C. coli demonstrated a
      higher degree of susceptibility than C. jejuni, however, there was no statistical
      difference (p = 0.2) comparing the linear trends over the duration of the study.
      There was no indication of frank macrolide (erythromycin or azithromycin)
      resistance among any Campylobacter. Moreover, there were statistically
      significant positive trends in both the MIC(50) and MIC(90) values for the
      erythromycin and azithromycin during the study period, suggesting a possible
      decreasing trend in susceptibility among Campylobacter. This study demonstrated
      that antimicrobial susceptibility in Campylobacter has significantly decreased
      from 1995 through 2000 among pediatric diarrhea cases in rural Egypt.

PMID- 14711483
TI  - Evaluation of Toxoplasma gondii recombinant proteins for the diagnosis of
      recently acquired toxoplasmosis by an immunoglobulin G analysis.
AB  - The value of T. gondii recombinant antigens rRop2, rGra4, rGra7 and rSAG1m
      (mature version) or rSAG1ct (C-terminal version) in differentiating recently
      acquired from chronic infections was determined by IgG-ELISA. The general highest
      sensitivity was observed with rRop2 whereas rSAG1m was not recognized by any of
      the serum samples, suggesting an incorrect folding. rGra4 and rGra7 showed
      significant higher sensitivity and absorbance values with serum samples from
      recently infected individuals compared to those with chronic infection. In
      contrast, rRop2 and rSAG1ct did not show differences in the reactivity pattern
      between both groups of serum samples.

PMID- 14711484
TI  - Comparison of the VERSANT HCV RNA qualitative assay (transcription-mediated
      amplification) and the COBAS AMPLICOR hepatitis C virus test, version 2.0, in
      patients undergoing interferon-ribavirin therapy.
AB  - Hepatitis C virus (HCV)-infected patients were tested for the presence of HCV RNA
      using two qualitative assays at various time points during interferon-ribavirin
      therapy. Among patients treated for 48 weeks, transcription-mediated
      amplification and the COBAS AMPLICOR Hepatitis C Virus Test results at Week 24
      predicted subsequent virologic non-response or virologic relapse in 12/15 (80%)
      and 8/15 (53%) patients, respectively.

PMID- 14711485
TI  - Improving typeability of multiple bacterial species using pulsed-field gel
      electrophoresis and thiourea.
AB  - Although pulsed-field gel electrophoresis is considered the "gold standard"
      technique for molecular typing, typeability may not be excellent for some
      bacterial species because of DNA degradation. Previous reports suggest that the
      addition of thiourea in the gel buffer can improved the typeability for some
      species. In the present study, 66 Gram-negative strains (seven species) known to
      be affected by DNA degradation and four control strains were evaluated by PFGE
      with and without the addition of 50 microg/M of thiourea to the buffer used in
      the electrophoresis. Macrorestriction patterns were obtained for all K.
      pneumoniae, S. marcescens, P. aeruginosa, and Salmonella spp., for 95.4% of E.
      coli, and for 50% of E. cloacae strains from the gels performed in the buffer
      with throurea. However, typeability was not improved for Acinetobacter spp. The
      range of non-typeable species for which thiourea can limit the problem of DNA
      degradation is considerably wider than described in previous publications.

PMID- 14711486
TI  - Molecular diagnosis of arthritis due to streptobacillus moniliformis.
AB  - Streptobacillus moniliformis was identified as etiologic agent of arthritis
      utilizing a 16S rDNA molecular kit in our clinical laboratory. With the
      increasing of human contacts with rat as pet, this method would appear suitable
      to identify fastidious Gram-negative rod involved in arthritis specially when the
      clinical context is not evocative.

PMID- 14711489
TI  - Infants' emerging ability to represent occluded object motion.
AB  - The emerging ability to represent an oscillating moving object over occlusions
      was studied in 7-21-week-old infants. The object moved at 0.25 Hz and was either
      occluded at the center of the trajectory (for 0.3 s) or at one turning point (for
      0.7 s). Each trial lasted for 20 s. Both eye and head movements were measured. By
      using two kinds of motion, sinusoidal (varying velocity) and triangular (constant
      velocity), infants' ability to take velocity change into account when predicting
      the reappearance of the moving object was tested. Over the age period studied,
      performance at the central occluder progressed from almost total ignorance of
      what happened to consistent predictive behavior. From around 12 weeks of age,
      infants began to form representations of the moving object that persisted over
      temporary occlusions. At around 5 months of age these representations began to
      incorporate the dynamics of the represented motion. Strong learning effects were
      obtained over single trials, but there was no evidence of retention between
      trials. The individual differences were profound.

PMID- 14711490
TI  - The role of historical intuitions in children's and adults' naming of artifacts.
AB  - It is commonly assumed that artifacts are named solely on the basis of properties
      they currently possess; in particular, their appearance and function. The
      experiments presented here explore the alternative proposal that the history of
      an artifact plays some role in how it is named. In three experiments, children
      between the ages of 4 and 9 years and adults were presented with familiar
      artifacts whose appearance and function were then radically altered. Participants
      were tested as to whether they believed that the modified objects were still
      members of the artifact kind. Results indicate that object history becomes
      increasingly important over the course of development.

PMID- 14711491
TI  - Cognitive profiling and preliminary subtyping in Chinese developmental dyslexia.
AB  - The present study examined the cognitive profile and subtypes of developmental
      dyslexia in a nonalphabetic script, Chinese. One hundred and forty-seven Chinese
      primary school children with developmental dyslexia were tested on a number of
      literacy and cognitive tasks. The results showed that rapid naming deficit and
      orthographic deficit were the two most dominant types of cognitive deficits in
      Chinese developmental dyslexia, and that rapid naming and orthographic processing
      had significant unique contributions to literacy performance. Seven subtypes of
      dyslexia--global deficit, orthographic deficit, phonological memory deficit, mild
      difficulty, and three other subtypes with rapid-naming-related deficits--were
      identified using scores of the cognitive tasks as classification measures in
      cluster analyses. These subtypes were validated with a behaviour checklist and
      three literacy measures. The authors suggested that orthographic and rapid naming
      deficits in Chinese dyslexic children might pose an interrelated problem in
      developing orthographic knowledge and representation. Therefore, orthographic
      related difficulties may be the crux of the problem in Chinese developmental
      dyslexia.

PMID- 14711492
TI  - Is there a causal link from phonological awareness to success in learning to
      read?
AB  - In this review, we re-assess the evidence that phonological awareness represents
      a skill specific to spoken language that precedes and directly influences the
      process of reading acquisition. Longitudinal and experimental training studies
      are examined in detail, as these are considered most appropriate for exploring a
      causal hypothesis of this nature. A particular focus of our analysis is the
      degree to which studies to date have controlled for existing literacy skills in
      their participants and the influence that these skills might have on performance
      on phonological awareness tasks. We conclude that no study has provided
      unequivocal evidence that there is a causal link from competence in phonological
      awareness to success in reading and spelling acquisition. However, we believe
      that such a study is possible and outline some ideas for its design and
      implementation.

PMID- 14711493
TI  - Improved recombinant gene expression in CHO cells using matrix attachment
      regions.
AB  - The use of animal cells such as Chinese hamster ovary (CHO) cells for recombinant
      gene expression provides many advantageous features such as proper folding and
      post-translational modification of the recombinant protein. However, recombinant
      genes introduced into animal cells are often expressed at low levels mainly due
      to position effects from the neighboring chromatin context. The tedious and time
      consuming selection and amplification procedure has been the major hurdle for
      using animal cell line such as CHO cells. To improve mammalian cell expression
      systems, we screened a variety of matrix/scaffold attachment region (MAR/SAR)
      elements for their ability to insulate transgene expression from the position
      effects in CHO cells. We found that the human beta-globin MAR element is
      particularly effective as the frequency of beta-Gal positive colonies was
      increased by up to 80%. The expression levels of these colonies were also
      enhanced about seven-fold. These improvements appear to be related to the
      increased copy numbers and a higher efficiency of expression of the integrated
      genes. When this element was used to express soluble TGF-beta type II receptor
      (sTbetaRII) through the gene amplification system, the frequency of colonies
      expressing detectable amounts of sTbetaRII was much higher than that of the
      control vector. We could also generate high sTbetaRII producers with uniform
      growth properties by a simple two-step amplification process involving two
      concentrations of methotrexate. This eliminates the need to isolate individual
      colonies followed by multi-step treatments of methotrexate and thereby greatly
      simplifies this mammalian expression system.

PMID- 14711494
TI  - Direct quantification of mRNA expression levels using single molecule detection.
AB  - Determination of the gene expression by direct quantification of mRNA is becoming
      increasingly important in basic, pharmaceutical and clinical research. We present
      a novel approach for gene quantification based on direct hybridization of gene
      specific probes to target mRNA sequences in solution at temperatures ensuring
      absolute specificity of the probe-target complex. No enzymatic steps like reverse
      transcription or amplification by PCR are involved within the quantification
      process. In order to increase specificity as well as sensitivity, two probes
      emitting fluorescence light in different colors are used for our homogeneous
      assay using fluorescence cross-correlation. We relate to the single molecule
      sensitivity of excitation and detection in confocal cavities avoiding the
      amplification of the detected signal. The analysis of the expression level of
      high, medium and low abundant genes is described in two different cell lines,
      whereby the genes are quantified in absolute numbers.

PMID- 14711495
TI  - Synthesis of the measles virus nucleoprotein in yeast Pichia pastoris and
      Saccharomyces cerevisiae.
AB  - The development of a simple, efficient and cost-effective system for generation
      of measles virus nucleoprotein might help to upgrade reagents for measles
      serology. The gene encoding measles nucleoprotein was successfully expressed in
      two different yeast genera, Pichia pastoris and Saccharomyces cerevisiae,
      respectively. Both yeast genera synthesized a high level of nucleoprotein, up to
      29 and 18% of total cell protein, in P. pastoris and S. cerevisiae, respectively.
      This protein is one of most abundantly expressed in yeast. After purification
      nucleocapsid-like particles (NLPs) derived from both yeast genera appeared to be
      similar to those detected in mammalian cells infected with measles virus. A
      spontaneous assembly of nucleoprotein into nucleocapsid-like particles in the
      absence of the viral leader RNA or viral proteins has been shown.
      Compartmentalisation of recombinant protein into large compact inclusions in the
      cytoplasm of yeast S. cerevisiae by green fluorescence protein (GFP) fusion has
      been demonstrated. Sera from measles patients reacted with the recombinant
      protein expressed in both yeast genera and a simple diagnostic assay to detect
      measles IgM could be designed on this basis.

PMID- 14711496
TI  - Recombinant proteins fused to thermostable partners can be purified by heat
      incubation.
AB  - We developed a protocol for the fast purification of small proteins and peptides
      using heat incubation as the first purification step. The proteins are expressed
      from a new bacterial expression vector (pETM-90) fused to the C-terminus of
      thermostable Ftr from Methanopyrus kandleri. The vector further contains a 6xHis
      tag to allow immobilised metal ion affinity purification and a TEV protease
      cleavage site to enable the removal of the His-tag and fusion partner. Heat
      incubation induces the specific denaturation and precipitation of the Escherichia
      coli proteins but not of the thermostable fusion protein. Using the fusion
      construct and the heat incubation protocol a number of fusion proteins were
      purified to near homogeneity. The thermostability was ensured when Ftr had a
      molecular weight higher than twice the target protein. The obtained purification
      yields were similar and, in some cases, even higher than the ones obtained by
      affinity purification with the same Ftr-fusion proteins or the same target
      proteins fused to other often used partners such as NusA, GST, or DsbA. The
      protocol does not depend on a specific thermostable protein as was shown by the
      exchange of Ftr for M. kandleri Mtd. Purification by heat incubation is a fast
      and inexpensive alternative to chromatographic techniques, particularly suitable
      for the production of antigenic sequences for which the loss of native structure
      is not detrimental. We proved that it can be easily automated.

PMID- 14711497
TI  - Expression, purification and characterization of recombinant sucrose synthase 1
      from Solanum tuberosum L. for carbohydrate engineering.
AB  - The gene sus1 from Solanum tuberosum L. encoding for sucrose synthase 1 was
      cloned into the plasmid pDR195 under the control of the PMA1 promotor. After
      transformation of Saccharomyces cerevisiae strain 22574d sus1 was constitutively
      expressed giving a specific activity of 0.3Umg(-1) protein in the crude extract.
      A one-step purification by Q-Sepharose resulted in an 14-fold purified enzyme
      preparation in 74% yield. SuSy1 was subsequently purified by immobilized metal
      ion affinity chromatography and characterized for its utilization in synthesizing
      different nucleotide sugars and sucrose analogues. The kinetic constants for the
      cleavage and synthesis reaction were determined: K(m) (UDP) 4microM; K(iS) (UDP)
      0.11mM; K(m) (sucrose) 91.6mM; K(m) (UDP-Glc) 0.5mM; K(iS) (UDP-Glc) 2.3mM; K(m)
      (D-fructose) 2.1mM; K(iS) (D-fructose) 35.9mM. Different nucleoside diphosphates
      as well as different donor substrate were accepted as follows:
      UDP>dTDP>ADP>CDP>GDP in the cleavage reaction and UDP-Glc>dTDP-Glc>ADP-Glc>CDP
      Glc in the synthesis reaction. SuSy1 shows also a broad acceptance of D- and L
      ketoses and D- and L-aldoses. The acceptance of aldoses was deduced from the
      binding of the inhibitor 5-deoxy-D-fructose (K(i) 0.3mM), an analogue of the
      natural substrate D-fructopyranoside. The broad substrate spectrum renders SuSy1
      from potato a versatile biocatalyst for carbohydrate engineering.

PMID- 14711498
TI  - Enzymatic esterification of beta-methylglucoside with acrylic/methacrylic acid in
      organic solvents.
AB  - The enzymatic esterifications of beta-methylglucoside with acrylic
      acid/methacrylic acid were carried out using Novozym 435. t-Butanol indicating
      the highest conversion value was determined as an optimal solvent. The molar
      ratio (beta-methylglucoside:acids) of 1:15 was most favorable to the
      esterification. The enzyme concentration of 5% (w/v), and the temperature (50
      degrees C for beta-methylglucoside:acrylic acid, 45 degrees C for beta
      methylglucoside:methacrylic acid) resulted in the highest final conversion. Beta
      methylglucoside of 60gl(-1) was found to be most effective in terms of short
      reaction time as well as product concentrations. Under these conditions, the
      maximum conversions for the esterification of beta-methylglucoside with acrylic
      acid and beta-methylglucoside with methacrylic acid were 59.3% after 12h and
      71.3% after 72h, respectively. The structural analysis of the products was
      performed by FT-IR spectroscopy and (1)H NMR.

PMID- 14711499
TI  - Production of tilapia insulin-like growth factor-2 in high cell density cultures
      of recombinant Escherichia coli.
AB  - An improved expression plasmid pET-insulin-like growth factor-2 (IGF2) was
      constructed and transferred into Escherichia coli BL21(DE3) for the expression of
      tilapia insulin-like growth factor-2. The recombinant insulin-like growth factor
      2 was produced as inclusion bodies, and the recombinant insulin-like growth
      factor-2 content was as high as 10.3% of the total protein content. For
      production of recombinant insulin-like growth factor-2 in E. coli, pH-stat fed
      batch cultures were used to achieve a high cell density culture. A cell
      concentration 183gl(-1) dry cell weight (DCW) was obtained after 30h cultivation
      and plasmid stability was maintained at high levels. Expression of insulin-like
      growth factor-2 was induced at three different cell concentrations, 50, 78.5, and
      114.5gl(-1) dry cell weight. When cells were induced at a cell concentration of
      114.5gl(-1) dry cell weight, the amount of insulin-like growth factor-2 produced
      was 9.69gl(-1) (11.3% of the total protein). Using a simple purification process
      including inclusion body isolation, denaturation, refolding and Ni-NTA affinity
      chromatography, 19.51mg of insulin-like growth factor-2 was obtained from a
      22.5ml of culture, and the recovery yield was 20.5%. The biological activity of
      the purified IGF-2 was demonstrated as promoting the growth of four different
      cell lines by the colorimetric bioassay and the best growth stimulation ratio was
      obtained for the Balb/3T3 clone 31A cell line.

PMID- 14711500
TI  - Transformation of terpenes using a Picea abies suspension culture.
AB  - When subjected to a Picea abies suspension cell culture, beta-pinene, either one
      of the pure enantiomers or the racemate, was transformed mainly to trans
      pinocarveol along with the minor products myrtenol, alpha-terpineol, pinocarvone,
      myrtenal and cis-pinocarveol. The absolute configuration of the major products
      corresponded to that of the starting beta-pinene enantiomer. Some of the primary
      transformation products, i.e. (1S)-cis- and (1S)-trans-pinocarveol, (1R)-myrtenol
      and (4S)-alpha-terpineol, were also tested as substrates of the P. abies
      suspension culture. They reacted more slowly than beta-pinene but, except for
      (4S)-alpha-terpineol, they were all transformed. Thus, (1R)-myrtenol was
      converted into both (1R)-myrtenal and (1R)-myrtanol, whereas (1S)-trans
      pinocarveol was converted into (1S)-pinocarvone. (4R)-Limonene was slowly
      transformed by the suspension culture into limonene-(1,2)-epoxide as the major
      product, with carveol, perillyl alcohol and 1,8-cineole as minor products.
      Autoxidation of terpenes in cell-free nutrient medium was investigated in detail.
      Alpha-pinene and beta-pinene were both autoxidized to a certain extent, while
      limonene remained unaffected. The rate of the autoxidation was more than one
      order of magnitude slower than that of the biotransformation. Moreover, different
      products were formed by autoxidation than by biotransformation.

PMID- 14711501
TI  - A new approach for fluorescence correlation spectroscopy (FCS) based
      immunoassays.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful technique for measuring
      physicochemical properties, such as concentration and diffusion constant, of bio
      molecules in complex mixtures. Although, as such, FCS is well suited for
      development of homogeneous immunoassays, a major obstacle lies in the relatively
      high molecular weight of antibodies. This is because in FCS discrimination
      between unbound fluorescently-labelled antibodies and the same antibodies bound
      to immune complexes is based on the difference of their respective diffusion
      coefficients. To overcome this limitation we here propose to use a fluorescently
      labelled tag which has two crucial properties: (a) its molecular weight is
      significantly lower than that of an antibody and (b) it is capable to
      discriminate between free antibodies and immune complexes. We have evaluated the
      feasibility of this approach in a model system consisting of mouse monoclonal IgG
      directed against the Lewis X antigen, and Protein A as a low molecular weight
      tag.

PMID- 14711502
TI  - Ionic interfaces and diphtheria toxoid interactions.
AB  - We present here a systematic study on the purification of the diphtheria toxoid
      (Dtxd) produced at the Instituto Butantan, by adding only one step on the entire
      process of its production. Aliquots of 1.0 ml of Dtxd were added to an equal
      amount of Q-Sepharose previously equilibrated with 500 mM Tris, pH 5.0-9.0
      (increments of 0.5 pH units). The best condition for the Dtxd monomer adsorption
      was achieved at pH 9.0. The best condition for desorption was obtained with 300
      mM NaCl. After studying the gel binding capacity for Dtxd, a column (C20/20)
      equilibrated with 500 mM Tris, pH 9.0, was prepared. The purification factor for
      Dtxd was 1.5. The final recovery of Dtxd was 68.75%, with 90.31% purity. The
      process methodology presented here is a very realistic sequence of separation
      steps, which is perfectly compatible with the production requirements.
      Vaccination with "toxoid highly purified toxin" is known to confer a strong
      immunity on people in the absence of undesirable reactions, which led experts of
      European Pharmacopoeia to recommend its use both for children and adult
      vaccination.

PMID- 14711503
TI  - Identification, cloning, and expression of bacteriophage T5 dnk gene encoding a
      broad specificity deoxyribonucleoside monophosphate kinase (EC 2.7.4.13).
AB  - The nucleotide sequence corresponding to 13-19.5% of the bacteriophage T5 genome
      in early region C was determined (GenBank AY 140897). One of the five major
      single-stranded interruptions (nicks) of bacteriophage T5 DNA was identified at
      18.5%. The sequenced region was annotated and the putative functions of some open
      reading frames were proposed by comparison with databases. The dnk gene, encoding
      a deoxyribonucleoside monophosphate kinase, was identified using a previously
      defined N-terminal amino acid sequence. The gene was cloned and expressed in
      Escherichia coli, the enzyme was purified to homogeneity with high yield using
      two alternative methods, and the recombinant deoxyribonucleoside monophosphate
      kinase was found to have the same activity and specificity as the native enzyme.

PMID- 14711504
TI  - Purification and characterization of the recombinant human dopamine D2S receptor
      from Pichia pastoris.
AB  - The human dopamine D2S receptor was expressed in the methylotrophic yeast Pichia
      pastoris, where the receptor with a molecular mass of approximately 40kDa
      exhibited specific and saturable binding properties. The dopamine antagonist
      [3H]spiperone showed an average dissociation constant K(d) of 0.6+/-0.17 nM for
      the dopamine D2S receptor. The receptor was solubilized using the non-ionic
      detergent dodecylmaltoside and purified by affinity chromatography using a Ni(2+)
      chelate (His-Trap) column or by batch extraction with an anti-FLAG M1 affinity
      resin. The receptor maintained its biological activity after solubilization and
      purification from the membrane protein fraction. A 244- or 185-fold enrichment,
      as judged by an increase in specific binding, was obtained after adsorption to
      the His-Trap or anti-FLAG materials, respectively.

PMID- 14711505
TI  - Expression and purification of human tryptophan hydroxylase from Escherichia coli
      and Pichia pastoris.
AB  - Tryptophan hydroxylase (TPH) from several mammalian species has previously been
      cloned and expressed in bacteria. However, due to the instability of wild type
      TPH, most successful attempts have been limited to the truncated forms of this
      enzyme. We have expressed full-length human TPH in large amounts in Escherichia
      coli and Pichia pastoris and purified the enzyme using new purification
      protocols. When expressed as a fusion protein in E. coli, the maltose-binding
      protein-TPH (MBP-TPH) fusion protein was more soluble than native TPH and the
      other fusion proteins and had a 3-fold higher specific activity than the His
      Patch-thioredoxin-TPH and 6xHis-TPH fusion proteins. The purified MBP-TPH had a
      V(max) of 296 nmol/min/mg and a K(m) for L-tryptophan of 7.5+/-0.7 microM,
      compared to 18+/-5 microM for the partially purified enzyme from P. pastoris. To
      overcome the unfavorable properties of TPH, the stabilizing effect of different
      agents was investigated. Both tryptophan and glycerol had a stabilizing effect,
      whereas dithiothreitol, (6R)-5,6,7,8,-tetrahydrobiopterin, and Fe(2+) inactivated
      the enzyme. Irrespective of expression conditions, both native TPH expressed in
      bacteria or yeast, or TPH fusion proteins expressed in bacteria exhibited a
      strong tendency to aggregate and precipitate during purification, indicating that
      this is an intrinsic property of this enzyme. This supports previous observations
      that the enzyme in vivo may be stabilized by additional interactions.

PMID- 14711506
TI  - A ribonuclease from Chinese ginseng (Panax ginseng) flowers.
AB  - A ribonuclease, with a molecular mass of 23kDa, and much higher activity toward
      poly(U) than poly(C) and only negligible activity toward poly(A) and poly(G), was
      isolated from the aqueous extract of Chinese ginseng (Panax ginseng) flowers. The
      ribonuclease was unadsorbed on diethylaminoethyl-cellulose and adsorbed on Affi
      gel blue gel and carboxymethyl-cellulose. High activity of the ribonuclease was
      maintained at pH 6-7. On either side of this pH range, there was a precipitous
      drop in enzyme activity. The activity of the enzyme peaked at 50 degrees C and
      fell to about 20% of the maximal activity when the temperature was lowered to 20
      degrees C or raised to 80 degrees C. The characteristics of this ribonuclease
      were different from those of ribonuclease previously purified from ginseng roots.

PMID- 14711507
TI  - N-terminal truncation circumvents proteolytic degradation of the human HtrA2/Omi
      serine protease in Escherichia coli: rapid purification of a proteolytically
      active HtrA2/Omi.
AB  - HtrA2/Omi, a mitochondrial trypsin-like serine protease, is pivotal in regulating
      apoptotic cell death; however, the underlying mechanism of HtrA2/Omi-mediated
      apoptosis remains to be elucidated. Using the pGEX bacterial expression system,
      we investigated the expression patterns of various forms of HtrA2/Omi. Full
      length mouse HtrA2/Omi (mHtrA2/Omi) was successfully expressed in E. coli and
      purified as a proteolytically active protein. In contrast, the expression of full
      length human HtrA2/Omi (hHtrA2/Omi) in E. coli was barely detected. On the basis
      of this result, we characterized further the expression patterns of N- or C
      terminally truncated hHtrA2/Omi proteins. We found that three copies of the
      PRAXXTXXTP motif, which exist only in hHtrA2/Omi, might serve as a primary site
      that is highly susceptible to proteolytic degradation by host proteases. Removal
      of the N-terminal region containing the PRAXXTXXTP motifs produced a form
      resistant to proteolytic degradation during expression in E. coli and
      purification, consequently improving the production of a catalytically active,
      mature hHtrA2/Omi. Our study provides a method for generating useful reagents to
      investigate molecular mechanism by which HtrA2/Omi contributes to regulating
      apoptotic cell death and to identify natural substrates of HtrA2/Omi.

PMID- 14711508
TI  - Cloning, expression, and purification of fumarase from the parasitic nematode
      Ascaris suum.
AB  - The cDNA encoding fumarase, an enzyme catalyzing reversible hydration of fumarate
      to L-malate, from the parasitic roundworm Ascaris suum, has been cloned,
      sequenced, over-expressed in Escherichia coli, and purified. The single open
      reading frame translates into a protein of 50,502Da containing 467 amino acids.
      It shows 82, 77, and 58% identity with Caenorhabditis elegans, human, and E. coli
      fumC fumarases, respectively. The A. suum fumarase shows the signature sequence
      motif (GSSIMPGKVNPTQCE), which defines not only the class II fumarase family but
      also a much broader superfamily of proteins containing GSSxMPxKxNPxxxE motif. The
      coding region was cloned into pET101D-directional TOPO expression vector and
      transformed into E. coli BL21 Star (DE3). The protein after induction was
      expressed at high levels, almost 10% of the soluble protein, purified to near
      homogeneity, and appears identical to the enzyme purified from Ascaris suum.

PMID- 14711509
TI  - Overproduction, purification, and characterization of the Plasmodium falciparum
      heat shock protein 70.
AB  - Plasmodium falciparum heat shock protein (PfHsp70) has been proposed to be
      involved in the cytoprotection of the malaria parasite through its action as a
      molecular chaperone. However, the biochemical and chaperone properties of PfHsp70
      have not been elucidated. The heterologous overproduction of P. falciparum
      proteins in Escherichia coli is problematic because of its AT-rich genome and the
      usage of codons that are rarely used in E. coli. In this paper, we describe the
      successful overproduction of (His)(6)-PfHsp70 in E. coli using the pQE30
      expression vector system. Initial experiments with E. coli [pQE30/PfHsp70]
      resulted in the overproduction of the full-length protein and truncated
      derivatives. The RIG plasmid, which encodes tRNAs for rare codons, was engineered
      into the E. coli [pQE30/PfHsp70] strain, resulting in significant reduction of
      the truncated (His)(6)-PfHsp70 derivatives and improved yields of the full-length
      protein. (His)(6)-PfHsp70 was successfully purified using nickel-chelating
      Sepharose affinity chromatography and its biochemical properties were determined.
      The V(max), K(m), and k(cat) for the basal ATPase activity of (His)(6)-PfHsp70
      were found to be 14.6 nmol/min/mg, 616.5 microM, and 1.03 min(-1), respectively.
      Gel filtration studies indicated that (His)(6)-PfHsp70 existed largely as a
      monomer in solution. This is the first study to biochemically describe PfHsp70
      and establishes a foundation for future studies on its chaperone properties.

PMID- 14711510
TI  - Expression, purification, and biochemical characterization of enteroaggregative
      Escherichia coli heat-stable enterotoxin 1.
AB  - Enteroaggregative Escherichia coli (EAEC) heat-stable enterotoxin 1 (EAST1) is a
      4.1k Da protein originally discovered in EAEC but known to be scattered in other
      diarrheagenic E. coli as well, possibly causing diarrhea in humans and animals.
      We report for the first time a method to express and purify EAST1 using the
      Glutathione S-transferase (GST) fusion system. The gst and astA genes were fused
      together on a pGEX-2T plasmid vector to produce a GST-EAST1 fusion protein. Using
      Glutathione Sepharose affinity chromatography and C(8) reverse phase high
      pressure liquid chromatography, EAST1 was purified to homogeneity with a yield of
      0.29 mg/L of culture. The protein purified by this method was confirmed to be
      EAST1 by NH(2)-terminal sequencing and mass spectrometry. The molecular weight of
      EAST1 is 4104.0 Da, confirming a 38 amino acid peptide as predicted by the astA
      gene sequence. Mass spectrometry analysis of EAST1 and of two generated peptides
      established the presence and suggested the position of two disulfide bridges of
      EAST1 in the conformations C1-C2 and C3-C4. Polyclonal antibodies were raised
      against EAST1 in New Zealand white rabbits to a titer of 1:8000 using affinity
      purified GST-EAST1 fusion protein and to a titer of 1:100 using HPLC-purified
      EAST1. The biological activity of various EAST1 preparations was tested using the
      suckling mouse assay with CD-1 and CFW mice strains, but failed to produce fluid
      accumulation in the intestine.

PMID- 14711511
TI  - Rapid, high-throughput purification of HIV-1 integrase using microtiter plate
      technology.
AB  - The human immunodeficiency virus type-1 (HIV-1) integrase (IN) catalyzes the
      insertion of the retroviral genome into the chromosome of an infected host cell.
      HIV-1 IN was expressed as a N-terminal hexa-histidine fusion in Escherichia coli.
      A high-throughput purification strategy was developed using denaturing methods
      for the initial protein extraction, followed by a one-step nickel-chelating
      chromatography purification and step-wise refolding. IN was routinely greater
      than 90% pure with yields exceeding 14 microg of purified IN per ml of E. coli
      culture. In vitro 3' processing and strand transfer assays showed the enzyme
      preparations to be highly active. The specific activity of the purified IN was
      2.65 pmol/h/microg IN, which is very similar to the activity of IN routinely
      produced by large-scale column chromatographic methods. This high-throughput
      platform should be of general utility to those interested in defining the
      structure-function relationship of proteins and enzymes.

PMID- 14711512
TI  - A novel multi-affinity tag system to produce high levels of soluble and
      biotinylated proteins in Escherichia coli.
AB  - We describe here a novel multi-affinity tag vector that can be used to produce
      high levels of soluble, in vivo biotinylated proteins in Escherichia coli. This
      system combines the solubility-enhancing ability of maltose-binding protein
      (MBP), the versatility of the hexahistidine tag (His(6)), and the site-specific
      in vivo biotinylation of a 15-amino acid tag (AviTag). We used this multi-tag
      system in an attempt to improve expression levels of two prokaryotic proteins
      elongation factor Tu (TufB) and DNA gyrase subunit A (GyrA)-as well as two
      eukaryotic nuclear receptors-glucocorticoid receptor (GR) and small heterodimer
      partner (SHP). The multi-tag system not only vastly improved the expression of
      the two prokaryotic proteins tested, but also yielded complete, site-specific, in
      vivo biotinylation of these proteins. The results obtained from the TufB
      expression and purification are presented and discussed in detail. The nuclear
      receptors, though soluble as fusion partners, failed to remain soluble once the
      MBP tag was cleaved. Despite this limitation of the system, the multi-affinity
      tag approach is a useful system that can improve expression of some otherwise
      insoluble or poorly expressing proteins, to obtain homogeneous, purified, fully
      biotinylated protein for downstream applications.

PMID- 14711513
TI  - Expression of human, mouse, and rat m-calpains in Escherichia coli and in murine
      fibroblasts.
AB  - The two best known calpains, micro- and m-calpain, are Ca(2+)-dependent cysteine
      proteases found in all mammalian tissues. They are probably involved in many
      Ca(2+)-linked signal pathways, although the details are not yet clear. The
      enzymes are heterodimers of a specific large subunit (micro-80k or m-80k) and a
      common small subunit (28k). Recombinant calpains have been obtained by co
      expression of large and small subunits in Escherichia coli and in Sf9 cells, with
      variable success. Expression with the 28k subunit is very low, but is much higher
      with a C-terminal 21k fragment of this subunit. Rat m-calpain (m-80k/21k) is well
      expressed in E. coli but mouse m-calpain (m-80k/21k) is poorly expressed, even
      though the amino acid sequences of rat-m-80k and mouse-m-80k are 92% identical.
      It had also been reported that human m-calpain could be expressed in Sf9 cells
      but not in E. coli. To investigate these differences, hybrid rat/mouse and
      rat/human m-calpains were cloned and expressed in E. coli. It was shown that Ile
      6 and Pro-127, which are specific to the mouse m-80k sequence, caused poor
      expression. High expression of human m-calpain in E. coli could be achieved by
      providing the correct Shine-Dalgarno ribosome binding site. The results provide a
      simple method to obtain approximately 10mg amounts of human m-calpain and a
      slightly modified mouse m-calpain. Expression of m-80k-EGFP fusions was also
      studied, both in E. coli and in mammalian cells, varying both the small subunit
      and the promoters. m-80k-EGFP alone was not active, but with 21k or 28k subunits
      was active in both cell types. The EGFP domain was partially cleaved during
      expression, releasing an active m-80k/21k calpain.

PMID- 14711514
TI  - Expression and rapid purification of highly active hexahistidine-tagged guinea
      pig liver transglutaminase.
AB  - Tissue transglutaminase has been identified as a contributor to a wide variety of
      diseases, including cataract formation and Celiac disease. Guinea pig tissue
      transglutaminase has a very broad substrate specificity and therefore is useful
      for kinetic studies using substrate analogues. Here, we report the expression in
      Escherichia coli of a hexahistidine-tagged guinea pig liver tissue
      transglutaminase (His(6)-tTGase) allowing rapid purification by immobilized-metal
      affinity chromatography. Using this procedure we have obtained the highest
      reported specific activity (17 U/mg) combined with a high yield (22 mg/L of
      culture) for recombinant TGase using a single-step purification protocol. Using
      two independent spectrophotometric assays, we determined that the K(m) value of
      the recombinant enzyme with the substrate Cbz-Gln-Gly is in the same range as
      values reported in the literature for the native enzyme. We have thus developed a
      rapid and reproducible protocol for the preparation of high quality tissue TGase.

PMID- 14711515
TI  - Purification of human haptoglobin 1-1, 2-1, and 2-2 using monoclonal antibody
      affinity chromatography.
AB  - Similar to blood type, human plasma haptoglobin (Hp) is classified as 3
      phenotypes: Hp 1-1, 2-1, or 2-2. The structural and functional relationship
      between the phenotypes, however, has not been studied in detail due to the
      complicated and difficult isolation procedures. This report provides a simple
      protocol that can be used to purify each Hp phenotype. Plasma was first passed
      through an affinity column coupled with a high affinity Hp monoclonal antibody.
      The bound material was washed with a buffer containing 0.2M NaCl and 0.02 M
      phosphate, pH 7.4, eluted at pH 11, and collected in tubes containing 1M Tris
      HCl, pH 6.8. The crude Hp fraction was then chromatographed on a HPLC Superose 12
      column in 0.05 M ammonium bicarbonate at a flow rate of 0.5 ml/min. The
      homogeneity of purified Hp 1-1, 2-1, or 2-2 was greater than 95% as judged by SDS
      polyacrylamide gel electrophoresis. Essentially, each Hp isolated was not
      contaminated with hemoglobin and apolipoprotein A-I as that reported from the
      other methods, and was able to bind hemoglobin. Neuraminidase treatment
      demonstrated that the purified Hp possessed a carbohydrate moiety, while Western
      blot analysis confirmed alpha and beta chains corresponding to each Hp 1-1, 2-1,
      and 2-2 phenotype. The procedures described here represent a significant
      improvement in current purification methods for the isolation of Hp phenotypes.
      Circular dichroic spectra showed that the alpha-helical content of Hp 1-1 (29%)
      was higher than that of Hp 2-1 (22%), and 2-2 (21%). The structural difference
      with respect to its clinical relevance is discussed.

PMID- 14711516
TI  - Expression, purification, and characterization of avian Thy-1 from Lec1 mammalian
      and Tn5 insect cells.
AB  - Structural studies of asparagine-linked glycoproteins are complicated by the
      oligosaccharide heterogeneity inherent to individual glycosylation sites. Herein,
      we report the cloning of a novel isoform of avian Thy-1 and the subsequent
      expression, purification, and characterization of a soluble form of Thy-1 from
      Lec1 mammalian and Tn5 insect cells. The novel isoform of Thy-1 differs from the
      previously reported chicken isoform by eight amino acid residues, but these
      changes do not alter the secondary structure content, the disulfide bond pattern,
      or the sites of glycosylation. The disulfide linkage pattern and glycoform
      distribution on each N-glycosylation site of recombinant chicken Thy-1 from both
      cell lines were determined by a combination of amino-terminal sequencing and mass
      spectrometry. The mass spectral data showed that the amino-terminal glutamine was
      modified to pyroglutamate. Recombinant Thy-1 from Lec1 cells contained
      (GlcNAc)(2)(Man)(5) on asparagine 60, whereas the oligosaccharides on asparagine
      23 and 100 contained approximately 80% (GlcNAc)(2)(Man)(4) and approximately 20%
      (GlcNAc)(2)(Man)(5). The glycoforms on Thy-1 expressed in Tn5 cells were more
      heterogeneous, with the oligosaccharides ranging over (GlcNAc)(2)(Fuc)(0
      2)(Man)(2-3) on each site. The ability to generate recombinant glycoproteins with
      restricted carbohydrate heterogeneity is the first step toward the systematic
      study of structure-function relationships in intact glycoproteins.

PMID- 14711517
TI  - A GapC chimera retains the properties of the Streptococcus uberis wild-type GapC
      protein.
AB  - The GapC products of Streptococcus agalactiae, Streptococcus dysgalactiae, and
      Streptococcus uberis share considerable homology at the DNA and amino acid
      levels. The high similarity at the protein level suggests that one GapC protein
      might be used as a single antigen to protect dairy cows against infections with
      the contagious S. agalactiae and the environmental S. dysgalactiae and S. uberis
      strains. Despite their similarities, immunization with the S. dysgalactiae GapC
      did not protect dairy cows from a challenge with S. uberis, suggesting the
      presence of regions in GapC that are involved in species-specific protection. To
      produce a single antigen that can be used to protect against all streptococcal
      mastitis infections, we constructed a GapC chimeric protein using the S. uberis
      GapC product as the backbone followed by non-conserved peptide regions from the
      S. agalactiae and S. dysgalactiae GapC proteins. We report that the chimeric GapC
      protein retains the enzymatic activity of the S. uberis GapC protein. In
      addition, we fused the chimera to the OmpF and LipoF transport sequences of
      Escherichia coli and the GapC chimeras were present in membrane fractions of E.
      coli. These extracts could be the basis of an antigen preparation for use in
      mastitis vaccines.

PMID- 14711518
TI  - Expression and purification of a small heat shock protein from the plant pathogen
      Xylella fastidiosa.
AB  - The small heat shock proteins (smHSPs) belong to a family of proteins that
      function as molecular chaperones by preventing protein aggregation and are also
      known to contain a conserved region termed alpha-crystallin domain. Here, we
      report the expression, purification, and partial characterization of a novel
      smHSP (HSP17.9) from the phytopathogen Xylella fastidiosa, causal agent of the
      citrus variegated chlorosis (CVC). The gene was cloned into a pET32-Xa/LIC vector
      to over-express the protein coupled with fusion tags in Escherichia coli
      BL21(DE3). The expressed HSP17.9 was purified by immobilized metal affinity
      chromatography (IMAC) and had its identity determined by mass spectrometry (MALDI
      TOF). The correct folding of the purified recombinant protein was verified by
      circular dichroism spectroscopy. Finally, the HSP17.9 protein also proved to
      efficiently prevent induced aggregation of insulin, strongly indicating a
      chaperone-like activity.

PMID- 14711519
TI  - Expression, purification, crystallization, and NMR studies of the helicase
      interaction domain of Escherichia coli DnaG primase.
AB  - In Escherichia coli, the DnaG primase is the RNA polymerase that synthesizes RNA
      primers at replication forks. It is composed of three domains, a small N-terminal
      zinc-binding domain, a larger central domain responsible for RNA synthesis, and a
      C-terminal domain comprising residues 434-581 [DnaG(434-581)] that interact with
      the hexameric DnaB helicase. Presumably because of this interaction, it had not
      been possible previously to express the C-terminal domain in a stably transformed
      E. coli strain. This problem was overcome by expression of DnaG(434-581) under
      control of tandem bacteriophage lambda-promoters, and the protein was purified in
      yields of 4-6 mg/L of culture and studied by NMR. A TOCSY spectrum of a 2mM
      solution of the protein at pH 7.0, indicated that its structured core comprises
      residues 444-579. This was consistent with sequence conservation among most
      closely related primases. Linewidths in a NOESY spectrum of a 0.5mM sample in
      10mM phosphate, pH 6.05, 0.1M NaCl, recorded at 36 degrees C, indicated the
      protein to be monomeric. Crystals of selenomethionine-substituted DnaG(434-581)
      obtained by the hanging-drop vapor-diffusion method were body-centered
      tetragonal, space group I4(1)22, with unit cell parameters a=b=142.2A, c=192.1A,
      and diffracted beyond 2.7A resolution with synchrotron radiation.

PMID- 14711520
TI  - Membrane protein expression and production: effects of polyhistidine tag length
      and position.
AB  - Polyhistidine tags enable the facile purification of proteins by immobilized
      metal affinity chromatography (IMAC). Both the type and position of purification
      tags can affect significantly properties of a protein such as its expression
      level, behavior in solution, and its ability to form suitable samples (esp.
      suitable crystals for X-ray crystallography). We investigated systematically the
      effects of polyhistidine tag length and position on many properties related to
      expression and purification of recombinant integral membrane proteins.
      Specifically, modified Escherichia coli pET expression vectors were built that
      placed 6- or 10-histidine tags at the N- or C-termini of the subcloned gene. The
      E. coli water channel AqpZ was subcloned into this suite of vectors and its
      expression, purification, solution properties, and yield were characterized.
      These studies show that: (1) all vectors yield similar expression levels, (2) tag
      length has a greater effect than tag position upon yield, (3) neither tag length
      nor position affects significantly detergent solubilization of the protein, (4)
      the length of the tag affects the oligomerization state of the purified protein,
      and (5) the tag length and position change chromatographic behavior of the
      detergent-solubilized protein. In addition, substitution of the lysine codon AAA
      at the second position, previously shown to have some effect upon soluble protein
      expression levels, did not have a large effect on AqpZ production. We are
      currently producing approximately 12 mg of purified AqpZ per liter of shake-flask
      culture, and preliminary crystals that diffract to approximately 5A resolution
      have been obtained.

PMID- 14711521
TI  - Improved production of recombinant fibroblast growth factor 7 (FGF7/KGF) from
      bacteria in high magnesium chloride.
AB  - Because of specificity for both heparin/heparan sulfate and the receptor complex
      on epithelial cells relative to other fibroblast growth factor (FGF) homologues,
      there is considerable interest in clinical and commercial applications of FGF7
      (also called keratinocyte growth factor or KGF) that require large quantities at
      reasonable cost. Production of recombinant FGF7 from bacteria suffers from lower
      yields and recovery relative to FGF1 and FGF2. Fusion of FGF7 at the N-terminus
      with glutathione-S-transferase (GST) followed by removal of GST by proteolysis
      while bound to natural ligand heparin improved the intrinsically low yields from
      Escherichia coli hosts to 3.2 mg per liter per OD(600), which was still only 10%
      of that for FGF1. Yield of the GST-FGF7 fusion product was improved to about 17
      mg per liter per OD(600) in strain BL21(DE3)pLysS by inclusion of 10-100mM
      magnesium chloride (MgCl(2)) in the culture medium. This improved by about five
      times the yields of fully active 54ser-FGF7 after proteolytic excision of the GST
      portion from GST-FGF7 immobilized on heparin-Sepharose. This simple enhancement
      improves the cost-effectiveness of production of recombinant FGF7 in bacteria for
      clinical and commercial applications.

PMID- 14711522
TI  - Purification and refolding of a novel cancer/testis antigen BJ-HCC-2 expressed in
      the inclusion bodies of Escherichia coli.
AB  - BJ-HCC-2 is one of the cancer/testis antigens that may be the most promising
      targets for tumor immunotherapy. To investigate the expression of BJ-HCC-2
      protein in tumor cells and its capacity to elicit CTL response, the recombinant
      protein of BJ-HCC-2 was expressed in the inclusion bodies in Escherichia coli.
      The inclusion bodies were solubilized effectively with 0.3% N-lauroyl sarcosine
      in alkaline buffer. Under this denatured form, the BJ-HCC-2 protein carrying 6x
      histidine tag was purified with Ni-NTA affinity chromatography in a single step
      with a purity of over 97%. The yield of the purified protein was about 78%. The
      purified recombinant protein was refolded in a simple way. The correct refolding
      of the recombinant protein was verified in the recovery of its secondary and
      tertiary structures as assessed by circular dichroism and fluorescence emission
      spectra. The recovery rate of refolded protein was 92.1%. The renatured protein
      displayed its immunoreactivity with the antibodies to BJ-HCC-2 protein by Western
      blotting. This method of protein purification and refolding is easy to manipulate
      and may be applicable to the hydrophobic proteins that are unable to be purified
      by other methods.

PMID- 14711523
TI  - Separation of latent, prelatent, and native forms of human antithrombin by
      heparin affinity high-performance liquid chromatography.
AB  - Latent antithrombin (LAT) is a partially denatured form of human antithrombin
      (AT). LAT does not inhibit clotting of the blood, but has previously been shown
      to inhibit angiogenesis and carcinogenesis. Another probably partially denatured
      form is the so-called prelatent AT (P-LAT), described by Larsson et al. [J. Biol.
      Chem. 276 (2001) 11996]. In the present work, an analytical heparin affinity
      chromatography method is described that separates an AT form, which is formed
      during the pasteurization process and which we believe to be identical to the
      previously described P-LAT, from native AT and LAT. Non-pasteurized AT was shown
      to contain no P-LAT, while four, heat-treated commercial AT products all
      contained P-LAT (1-6%, mean=4%). P-LAT has a slightly lower affinity to heparin
      than does native AT, but exhibits a much stronger heparin affinity when compared
      to LAT. P-LAT and native AT were shown to have very similar thrombin inhibiting
      activity, while LAT lacks such activity.

PMID- 14711524
TI  - Mu dI1(Ap lac) mutagenesis of Yersinia pestis plasmid pFra and identification of
      temperature-regulated loci associated with virulence.
AB  - The F1 capsule of Yersinia pestis, encoded by the 100 kb plasmid pFra, is often
      assumed to be essential for full virulence of Y. pestis. However, virulent
      strains of Y. pestis that are F1- and either pFra+ or pFra- have been reported.
      To assess the role of pFra-encoded factors in virulence, mutants in pFra with
      insertions of the defective transposing bacteriophage Mu dl(Ap lac) were
      obtained, by using the wild type (wt) and the pLcr-cured derivative of strain
      C092. Mutants that exhibited temperature regulation of lactose fermentation and
      retarded electrophoretic mobility of pFra were selected. A total of 15 insertion
      mutants were isolated in the wt strain (12 of which had a single insertion in the
      genome, in pFra); and 24 mutants in the isogenic pLcr- derivative. Four of the
      pLcr+ mutants, and none of the pLcr- mutants, were F1-. All F1- mutants were
      decreased in virulence for mice compared to the wt parent; and five of the F1+
      mutants also were significantly attenuated in mice. Fusion end-joints of insert
      DNA were cloned into Escherichia coli by using pMLB524, a vector for rescuing
      operon fusions of lacZ. Recombinants were obtained which contained pFra inserts
      ranging from < 2kb to approximately 36 kb, and the insertions occurred at several
      sites on pFra. All of the four F1- mutants tested mapped within the F1 capsule
      operon (caf1). The remaining five attenuated mutants sequenced were F1+ and
      mapped outside of but near the operon. Sequencing and complete analysis of the
      pFra insertions mutants could facilitate identification of new potential
      virulence factors.

PMID- 14711525
TI  - Structural comparison of the integrative and conjugative elements R391, pMERPH,
      R997, and SXT.
AB  - R391 and SXT are members of a group of eleven chromosome-borne conjugative
      elements found in the gamma-proteobacteria, whose members carry different
      antibiotic resistance traits. Recent genomic analysis of R391 and SXT revealed a
      highly conserved 'backbone' encoding integration/excision, conjugative transfer,
      and regulation functions, augmented by an array of phenotypic traits and
      transposable elements. In this study, PCR amplification and sequence analysis
      were employed to investigate the genomic structure of two further MGE of the R391
      family, pMERPH (HgR) and R997 (ApR, SmR, SuR). R997 and pMERPH were found to be
      structurally related to R391 and SXT and share a number of virtually identical
      regions with them-including putative integration, conjugative transfer, and
      regulatory determinants-interrupted by variable DNA segments and transposable
      elements. The presence of a highly conserved backbone in the four elements
      strongly suggests their origin in a common ancestral element, which itself was a
      mosaic of sequences related to phages and plasmids. Subsequent genetic
      recombination and the acquisition of transposable elements resulted in the
      possession of variable phenotypic traits among the four MGE, and diversification
      into two distinct lineages, the first one including R391 and pMERPH, the second
      one containing SXT and R997.

PMID- 14711526
TI  - Characterization of a theta-replicating plasmid from Streptococcus thermophilus.
AB  - Plasmids of Streptococcus thermophilus were previously classified, based on DNA
      homology, into at least four groups (A-D). Here, we report the characterization
      of plasmids of group B and D. The sequence analysis of pSMQ173b (group D)
      indicates that this plasmid contains 4449 bp, five open reading frames (ORFs) and
      replicates via the rolling-circle mechanism of the pGI3 family. The plasmid
      pSMQ308 (group B) contains 8144 bp and six ORFs. Two ORFs likely encode a
      primase/helicase and an integrase. Northern blot experiments demonstrate that
      these two orfs are transcribed within the three strains containing plasmids of
      group B. Two-dimensional agarose gel electrophoresis shows that pSMQ308
      replicates via a theta mechanism. To our knowledge, this is the first report of a
      plasmid replicating via a theta mode in S. thermophilus. Finally, a
      classification of 20 sequenced S. thermophilus plasmids into six groups based on
      their mode of replication is proposed.

PMID- 14711527
TI  - Plasmid curing of Oenococcus oeni.
AB  - Two strains of Oenococcus oeni, RS1 (which carries the plasmid pRS1) and RS2
      (which carries the plasmids pRS2 and pRS3), were grown in the presence of
      different curing agents and at different temperatures. Sublethal temperature
      together with acriflavine generated all possible types of cured strains, i.e.,
      lacking pRS1 (from strain RS1), and lacking pRS2, pRS3, or both (from strain
      RS2). Sublethal temperature together with acridine orange only generated cured
      strains lacking pRS3. These results suggest that acriflavine is a better curing
      agent than acridine orange for O. oeni, and that pRS3 is the most sensitive to
      these curing agents. We also observed spontaneous loss of pRS2 or both pRS2 and
      pRS3 by electroporation. The ability to cure O. oeni strains of plasmids provides
      a critical new tool for the genetic analysis and engineering of this commercially
      important bacterium.

PMID- 14711528
TI  - Analysis of the complete nucleotide sequence of an Actinobacillus
      pleuropneumoniae streptomycin-sulfonamide resistance plasmid, pMS260.
AB  - pMS260 is an 8.1-kb non-conjugative but mobilizable plasmid that was isolated
      from Actinobacillus pleuropneumoniae and encodes streptomycin (SM) and
      sulfonamide (SA) resistances. The analysis of the complete nucleotide sequence of
      the plasmid revealed a high degree of similarity between pMS260 and the broad
      host-range IncQ family plasmids. pMS260 had a single copy of an origin of
      vegetative replication (oriV). This sequence was identical to a functional oriV
      of the IncQ-like plasmid pIE1130 that had been exogenously isolated from piggery
      manure. However, pMS260 did not carry the second IncQ plasmid RSF1010-like oriV
      region present in pIE1130. A pIE1130-identical transfer origin was also found in
      pMS260. In addition, the deduced amino acid sequences from 10 open reading frames
      identified in pMS260 were entirely or nearly identical to those from genes for
      the replication, mobilization, and SM-SA resistance of pIE1130, indicating that
      pMS260 belongs to the IncQ-1 gamma subgroup. pMS260 is physically
      indistinguishable from pIE1130 apart from two DNA regions that contain the
      chloramphenicol and kanamycin resistance genes (catIII and aphI, respectively)
      and the second oriV-like region of pIE1130. The codon bias analysis of each gene
      of pIE1130 and the presence of potential recombination sites in the sulII-strA
      intergenic regions suggest that pIE1130 seems to have acquired the catIII and
      aphI genes more recently than the other genes of pIE1130. Therefore, pMS260 may
      be the ancestor of pIE1130. Information regarding the broad-host-range replicon
      of pMS260 will be useful in the development of genetic systems for a wide range
      of bacteria including A. pleuropneumoniae.

PMID- 14711529
TI  - The SHV-5 extended-spectrum beta-lactamase gene of pACM1 is located on the
      remnant of a compound transposon.
AB  - The SHV-5 extended-spectrum beta-lactamase gene of pACM1 was previously shown to
      reside on a segment of DNA ( approximately 7.9 kb) homologous to part of the
      Klebsiella pneumoniae chromosome. Regions of pACM1 overlapping the ends of the
      homology were sequenced. A defective copy of IS26 was found on each side of, and
      immediately adjacent to, the homology. The copies were oriented as direct repeats
      reminiscent of the compound transposon Tn2680. Other mobile elements and a
      putative mutagenesis gene, several of which were also defective, were also
      located in the vicinity of the homology. An intact precursor to the transposon
      remnant might have contributed to the dissemination of the SHV-5 gene.

PMID- 14711530
TI  - Characterization of the cryptic plasmid pCC1 from Corynebacterium callunae and
      its use for vector construction.
AB  - The complete nucleotide sequence of the cryptic plasmid pCC1 from Corynebacterium
      callunae (4109 bp) was determined. DNA sequence analysis revealed five open
      reading frames longer than 200 bp. One of the deduced polypeptides showed
      homology with the Rep proteins encoded by plasmids of the pIJ101/pJV1 family of
      plasmids replicating by the rolling-circle (RC) mechanism. Within this plasmid
      family, the Rep protein of pCC1 showed the highest degree of similarity to the
      Rep proteins of corynebacterial plasmids pAG3 and pBL1. These data suggest that
      the plasmid pCC1 replicates by the RC mechanism. The Escherichia
      coli/Corynebacterium glutamicum shuttle cloning vector pSCCD1, carrying the pCC1
      rep gene on the 2.1-kb DNA fragment and the streptomycin/spectinomycin resistance
      determinant, was constructed. This vector is stably maintained in population of
      C. glutamicum cells grown in the absence of selection pressure and it is
      compatible with plasmid vectors based on corynebacterial plasmids pBL1 and pSR1.

PMID- 14711531
TI  - Sequence analysis of plasmid pTS1 isolated from oral spirochetes.
AB  - The naturally occurring plasmid pTS1, identified previously in several species of
      oral spirochetes, has now been completely sequenced. Analysis of the four open
      reading frames identified on the plasmid suggests the presence of genes involved
      in replication and mobilization.

PMID- 14711532
TI  - Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to
      prevention of ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To review the available knowledge on the use of GnRH agonist for
      ovulation triggering as a means to prevent ovarian hyperstimulation syndrome
      (OHSS). DESIGN(S): Review of pertinent English language studies published over
      the past 15 years. RESULT(S): The available literature suggests that while GnRH
      agonist effectively induces final oocyte maturation and ovulation, it also
      completely and reliably prevents clinically significant OHSS. The mechanism of
      action in the context of OHSS prevention involves complete, quick, and
      irreversible luteolysis CONCLUSION(S): Controlled ovarian stimulation protocols
      based on GnRH antagonist to prevent premature LH rise and GnRH agonist for
      ovulation triggering provide a safe and OHSS-free clinical environment. Adequate
      luteal support compensates for luteolysis and assures good clinical outcome. The
      fertility community is urged to adopt these protocols. This will make OHSS a
      disease of the past.

PMID- 14711533
TI  - The limited clinical usefulness of taking a history in the evaluation of women
      with tubal factor infertility.
AB  - OBJECTIVE: To evaluate whether patient histories of gynecological infections
      predict tubal pathology seen at laparoscopic exam in infertile women. DESIGN:
      Cross-sectional analysis from a subset of case-control subjects. SETTING:
      Tertiary-level public hospitals with infertility clinics, Mexico City.
      PATIENT(S): Three hundred twenty-one nulligravid infertile women seeking
      diagnostic workup. INTERVENTION(S): Interviews conducted before evaluation by
      laparoscopy. MAIN OUTCOME MEASURES(S): Sensitivity, specificity, and predictive
      values for correlating previous pelvic inflammatory disease symptoms, vaginal
      discharge, genital tract infections, and antibodies to Chlamydia trachomatis to
      confirmed diagnoses of tubal pathology and to severe tubal pathology. RESULT(S):
      Tubal pathology was found in 58% of participants (n = 185), and severe pathology
      was found in 29% (n = 92). None of the historical infection-related factors alone
      was a good overall predictor of tubal pathology; high sensitivity values (up to
      73%) were offset by low specificity (down to 30%) and vice versa, for each
      factor. When considered simultaneously, the factors improved the overall
      predictive ability just slightly (84% sensitivity and 29% specificity) over the
      individual factors. The validity measures did not improve when examining severe
      tubal pathology alone. CONCLUSION(S): History taking related to past genital
      tract infections appears to be of little use in the evaluation of infertile
      women.

PMID- 14711534
TI  - The art of taking a history.
AB  - The standard questionnaire is a tool to collect information for a survey, but its
      validity for patient management is doubtful. Taking a history is a skill that
      cannot be replaced by a questionnaire.

PMID- 14711535
TI  - Clinical history is the essence of medicine.
AB  - Taking a history is useful in the evaluation of women with tubal factor
      infertility. A clinical history also predicts those women who will benefit from
      surgical therapy.

PMID- 14711536
TI  - Taking a history in the evaluation of infertility: obsolete or venerable
      tradition?
AB  - Taking a relevant history that includes pelvic inflammatory disease or exposure
      to sexually transmitted diseases is not obsolete.

PMID- 14711538
TI  - Revised 2003 consensus on diagnostic criteria and long-term health risks related
      to polycystic ovary syndrome.
AB  - Since the 1990 National Institutes of Health-sponsored conference on polycystic
      ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a
      broader spectrum of signs and symptoms of ovarian dysfunction than those defined
      by the original diagnostic criteria. The 2003 Rotterdam consensus workshop
      concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal
      features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a
      syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or
      PCO) is sufficient for clinical diagnosis. Its clinical manifestations may
      include menstrual irregularities, signs of androgen excess, and obesity. Insulin
      resistance and elevated serum LH levels are also common features in PCOS. PCOS is
      associated with an increased risk of type 2 diabetes and cardiovascular events.

PMID- 14711540
TI  - The development and impact of culture media for assisted reproductive
      technologies.
AB  - Changes in the composition of media used for human in vitro fertilization and
      embryo culture are reviewed, and their impact on improved pregnancy rates is
      discussed. It is concluded that changes to the formulation of culture media for
      assisted reproductive technologies over the past decade have played a significant
      role in improving outcomes from assisted reproductive technologies procedures
      involving the culture of embryos.

PMID- 14711541
TI  - Preimplantation diagnosis of repeated miscarriage due to chromosomal
      translocations using metaphase chromosomes of a blastomere biopsied from 4- to 6
      cell-stage embryos.
AB  - OBJECTIVE: To evaluate the safety and accuracy of karyotyping the blastomere
      chromosomes at metaphase in the natural cell cycle for preimplantation diagnosis.
      DESIGN: A pilot study. SETTING: A private infertility clinic and a university
      laboratory. PATIENT(S): Eleven patients undergoing IVF and preimplantation
      diagnosis. INTERVENTION(S): Intact human embryos at the 4- to 6-cell stage and
      human-mouse heterokaryons were cultured and checked hourly for disappearance of
      the nuclear envelope. After it disappeared, the metaphase chromosomes were
      analyzed by fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S):
      Percentage of analyzable metaphase plates and safety and accuracy of the method.
      RESULT(S): The success rate of electrofusion to form human-mouse heterokaryons
      was 87.1% (27/31), and analyzable chromosomes were obtained from 77.4% (24/31) of
      the heterokaryons. On the other hand, disappearance of the nuclear envelope
      occurred in 89.5% (17/19) of the human embryos and it began earlier than that in
      the heterokaryons. Analyzable chromosomes were obtained and their translocation
      sites were identified in all blastomeres biopsied from the 17 embryos. After the
      biopsy, 67.0% of the embryos could develop to the blastocyst stage.
      CONCLUSION(S): The natural cell cycle method reported herein requires frequent
      observation, but it is safe, with no artificial effects on the chromosomes and
      without loss of or damage to blastomeres, which occurred with the electrofusion
      method. Using the natural cell cycle method, we could perform preimplantation
      diagnosis with nearly 100% accuracy.

PMID- 14711542
TI  - Impact of repeated antral follicle counts on the prediction of poor ovarian
      response in women undergoing in vitro fertilization.
AB  - OBJECTIVE: To study the value of a single antral follicle count and the
      additional value of repeated counts in different cycles for the prediction of
      poor ovarian response in IVF. DESIGN: Prospective. SETTING: Tertiary fertility
      center. PATIENT(S): One hundred twenty women undergoing their first IVF cycle.
      INTERVENTION(S): Measurement of the number of antral follicles on cycle day 3 in
      two spontaneous cycles. Ovarian response. RESULT(S): A single antral follicle
      count is clearly predictive of poor ovarian response and there is good agreement
      between repeated measurements in subsequent cycles (area under the receiver
      operating characteristic curve [ROC(AUC)]; cycle 1: 0.87, cycle 2: 0.85). In a
      logistic regression analysis, information obtained after the second cycle
      contributed significantly to the prediction of poor response by the antral
      follicle count of the first cycle. The predictive accuracy of the highest of two
      counts (ROC(AUC) 0.89) was slightly better than that of each single count. The
      predictive model with the highest count yielded slightly higher values of
      specificity and positive predictive value. Sensitivity, negative predictive
      value, and error rates were slightly lower. CONCLUSION(S): A single antral
      follicle count is a good predictor of poor ovarian response in IVF. Although the
      impact of a second antral follicle count on ovarian response predictions in IVF
      is statistically significant, clinical relevance is very limited. Repeating an
      antral follicle count in a subsequent cycle is not recommended.

PMID- 14711543
TI  - A randomized, double-blind, controlled trial of the effect of adding follicular
      fluid meiosis activating sterol in an ethanol formulation to donated human
      cumulus-enclosed oocytes before fertilization.
AB  - OBJECTIVE: To evaluate the effect of follicular fluid meiosis activating sterol
      (FF-MAS) in a 0.2% ethanol formulation on chromosomal status and development of
      preembryos. DESIGN: Multicenter, prospective, randomized, double-blind, five
      parallel group, controlled trial. SETTING: Public and private IVF-clinics in
      Denmark and Sweden. PATIENT(S): Two hundred ten women undergoing IVF treatment
      donated 310 oocytes. INTERVENTIONS(S): FSH/hCG primed cumulus-enclosed oocytes
      randomized to 4 hours exposure of medium with 0.1, 1, or 10 microM FF-MAS
      dissolved in 0.2% ethanol, medium with ethanol 0.2%, or medium with water for
      injection (control) before insemination. MAIN OUTCOME MEASURE(S): Primary:
      incidence of human preembryos with chromosomal abnormalities. Secondary:
      fertilization rate, cleavage rate, and preembryo quality after 68 hours of
      culture. RESULT(S): At the preembryo level, no significant differences in
      chromosomal abnormality rate were found among any of the groups. At the
      blastomere level, a significant increased abnormality rate was observed in the
      ethanol group and the combined FF-MAS groups compared with the control group. No
      significant differences in fertilization rate, cleavage rate, or preembryo
      quality were observed among any of the groups and the control group except for a
      significant reduction in the number of embryos with >or=2 cells at 26 hours in
      the ethanol group. CONCLUSION(S): No negative effect of FF-MAS was observed.
      However, addition of ethanol 0.2% to standard IVF-medium with or without FF-MAS
      for culturing cumulus-enclosed oocytes for 4 hours before insemination increased
      the chromosomal abnormality rate at the blastomere level. Further studies of FF
      MAS in a nonethanol formulation are under way.

PMID- 14711544
TI  - Influence of embryo transfer depth on in vitro fertilization and embryo transfer
      outcomes.
AB  - OBJECTIVE: To investigate the influence of transfer distance from the fundus
      (TDF) on clinical pregnancy rate (PR) and ectopic pregnancy rate. DESIGN:
      Retrospective cohort. Between January 2000 and December 2001, 699 ultrasound (US)
      guided embryo transfers were conducted. Mock transfer was performed to measure
      uterine cavity depth 1 month before treatment. Cavity depth was measured by
      abdominal US before the transfer, from the vaginal stripe to the fundus.
      Transfers were performed with a Wallace embryo transfer catheter (Cooper
      Surgical, Shelton, CT) using US and physician's judgment of cavity depth.
      Transfer distance from the fundus was calculated by subtracting the depth of
      catheter insertion from the cavity depth, as determined by US or by mock
      transfer. Statistical analyses were performed by building a multivariable
      logistic regression model to calculate odds ratios and 95% confidence intervals
      (CI). SETTING: Women aged 23 to 43 years who are in a university-affiliated,
      community-based IVF program in Springfield, Massachusetts. PATIENT(S): All
      patients enrolled in IVF program undergoing embryo transfer. INTERVENTION(S): No
      patient received any additional procedure or intervention. All of the
      measurements obtained with the embryo catheter and the transvaginal ultrasound
      were part of the program's protocol for the embryo transfer. MAIN OUTCOME
      MEASURE(S): Odds ratio examining relationship between embryo transfer depth and
      PR.Clinical, implantation, and ectopic PR were 37%, 20%, and 2.1%. Cavity depth
      by US differed from cavity depth by mock by at least 10 mm in >30% of cases. The
      TDF by US was highly predictive of PR; TDF by mock was not predictive of PR.
      Increasing the TDF by US resulted in significantly increased PR as well as lower
      ectopic rates. Using regression analysis, the odds ratio for TDF by US was 1.11
      (95% CI: 1.07-1.14). This suggests that for every additional millimeter embryos
      are deposited away from the fundus, the odds of clinical pregnancy increased by
      11%. CONCLUSION(S): After controlling for potential confounders, the clinical PR
      is significantly influenced by the transfer distance from the fundus. Cavity
      depth by US is clinically useful to determine the depth beyond which catheter
      insertion should not occur.

PMID- 14711545
TI  - A new role for natural killer cells, interleukin (IL)-12, and IL-18 in repeated
      implantation failure after in vitro fertilization.
AB  - OBJECTIVE: To investigate the endometrial immunohistochemical staining of
      interleukin (IL)-12 and IL-18 and to quantify the CD56 bright natural killer (NK)
      cells in relation to Doppler vascular disorders. DESIGN: Controlled clinical
      study. SETTING: Research unit of a university hospital. PATIENT(S)": Thirty-five
      women with repeated implantation failure after ET in IVF and 12 fertile control
      patients.Ultrasound evaluation and endometrial biopsy on day 20. MAIN OUTCOME
      MEASURE(S): The balance between IL-12 and IL-18, the number of NK cells, and the
      vascular status among fertile and implantation failure patients. RESULT(S): The
      control patients displayed normal vascular parameters, a weak anti-IL-12
      staining, a consistent moderate stromal anti-IL-18 staining, and fewer than 15 NK
      cells/field. This pattern was observed among only 17% (6/35) of the implantation
      failure group. The remaining patients fit into one of two patterns: [1] 37%
      (13/35) had more than 40 NK cells/field with a strong anti-IL-12 and/or anti-IL
      18 staining, and [2] the remaining 46% (16/35) had a marked local depletion of IL
      18 and IL-12. Respectively, 85% and 31% of two groups displayed abnormal vascular
      parameters. CONCLUSION(S): Distinctions between the different local
      dysregulations of the cytokine network may provide clues for further exploration
      and treatment.

PMID- 14711546
TI  - Use of serum inhibin A and human chorionic gonadotropin measurements to predict
      the outcome of in vitro fertilization pregnancies.
AB  - OBJECTIVE: To assess the clinical value of maternal serum inhibin A measurements
      in early pregnancy in the prediction of outcome of IVF pregnancies and to compare
      the predictive accuracy of inhibin A concentrations with serum hCG
      concentrations. DESIGN: Retrospective study.University-based IVF program.
      PATIENT(S): One hundred fifty IVF pregnancies of 150 couples were studied during
      a 4-year period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association
      between pregnancy outcome and age, number of collected oocytes, number of
      transferred embryos, and serum hCG and inhibin A concentrations in early
      pregnancy was studied with logistic regression. Predictive accuracy of inhibin A
      and hCG concentrations was calculated by receiver-operating characteristic (ROC)
      analysis. RESULT(S): Lower serum concentrations of inhibin A and hCG were
      associated with increased odds for preclinical abortion and early pregnancy loss,
      whereas higher inhibin A and hCG concentrations were observed in multiple ongoing
      pregnancies. Inhibin A measurements were superior to hCG in the prediction of
      preclinical abortions; no significant difference was observed between the
      predictive value of hCG, inhibin A, or their combination in differentiating
      between ongoing pregnancies and early pregnancy losses. The discriminative
      potential of inhibin A for prognosticating multiple ongoing pregnancies was lower
      than that of hCG. CONCLUSION(S): Although serum inhibin A concentrations are more
      accurate than hCG levels for predicting preclinical abortion after IVF, they had
      no advantage in forecasting ongoing or multiple ongoing pregnancies, suggesting
      that routine assessment of serum inhibin A concentrations during follow-up of IVF
      pregnancies is unjustified.

PMID- 14711547
TI  - Comparison of mitochondrial DNA contents in human embryos with good or poor
      morphology at the 8-cell stage.
AB  - OBJECTIVE: To quantify the mitochondrial DNA contents in human embryos with good
      or poor quality at the 8-cell stage. DESIGN: Prospective study. SETTING: Private
      infertility clinic. PATIENT(S): Five women aged 24 to 34 years. INTERVENTION(S):
      Embryos obtained in standard superovulation and embryo culture procedures. MAIN
      OUTCOME MEASURE(S): Mitochondrial DNA (mtDNA) copy numbers in human embryos at
      cleavage stage were quantified by real-time polymerase chain reaction, in an
      effort to correlate with morphology. RESULT(S): The grade 8A embryos contained a
      mean mtDNA copy number at 1163937 (n = 8, from three patients); grade 8B embryos,
      at 939345 (n = 5, from two patients); grade 8C(+) embryos, at 637872 (n = 12,
      from 5 patients); and grade 8C(+) embryos derived from 3PN zygotes, at 300429 (n
      = 3, from a single patient). CONCLUSION(S): Great variations were found among
      blastomeres from a single embryo and among embryos from a single patient. The
      native variations of mtDNA copy number may affect developmental ability
      irrespective of morphology.

PMID- 14711548
TI  - Use of frozen semen to avoid human immunodeficiency virus type 1 transmission by
      donor insemination: a cost-effectiveness analysis.
AB  - OBJECTIVE: Reappraisal of current guidelines mandating frozen-thawed semen.
      DESIGN: Cost-effectiveness analysis comparing the use of frozen semen with the
      use of fresh semen from the same donors without a second antibody test. SETTING:
      A Markov model computer simulation. PATIENT(S): A theoretical cohort of 80000
      women whose husbands are azoospermic. INTERVENTION(S): Simulation with
      calculation of costs and payoffs. MAIN OUTCOME MEASURE(S): Total lifetime direct
      health care costs, costs per live birth, life expectancy, quality adjusted life
      years (QALY), marginal cost effectiveness (dollar/QALY). RESULT(S): If all 80000
      women who undergo donor insemination in the United States each year chose to use
      fresh semen from donors screened according to the current practice guidelines but
      without semen cryopreservation, there would be 8881 more births and the mean cost
      per live birth would be US dollars 15501 less. One recipient would become
      infected with HIV-1 every 5.1 years, during which time over 180000 noninfected
      children would be born. The average life expectancy of recipients would be
      reduced by 2 days, but their quality-adjusted life expectancy would increase by
      over 1 month. Medicolegal costs to physicians would need to exceed US dollars 780
      million per infection to equalize the cost effectiveness of the fresh and frozen
      policies. CONCLUSION(S): The guidelines should be revised to allow the use of
      fresh semen by informed recipients.

PMID- 14711549
TI  - Coenzyme Q(10) supplementation in infertile men with idiopathic
      asthenozoospermia: an open, uncontrolled pilot study.
AB  - OBJECTIVE: To clarify a potential therapeutic role of coenzyme Q(10) (CoQ(10)) in
      infertile men with idiopathic asthenozoospermia. DESIGN: Open, uncontrolled pilot
      study. PATIENT(S): Infertile men with idiopathic asthenozoospermia.
      INTERVENTION(S): CoQ(10) was administered orally; semen samples were collected at
      baseline and after 6 months of therapy. MAIN OUTCOME MEASURE (S): Semen kinetic
      parameters, including computer-assisted sperm data and CoQ(10) and
      phosphatidylcholine levels. RESULT(S): CoQ(10) levels increased significantly in
      seminal plasma and in sperm cells after treatment. Phosphatidylcholine levels
      also increased. A significant increase was also found in sperm cell motility as
      confirmed by computer-assisted analysis. A positive dependence (using the
      Cramer's index of association) was evident among the relative variations,
      baseline and after treatment, of seminal plasma or intracellular CoQ(10) content
      and computer-determined kinetic parameters. CONCLUSION(S): The exogenous
      administration of CoQ(10) may play a positive role in the treatment of
      asthenozoospermia. This is probably the result of its role in mitochondrial
      bioenergetics and its antioxidant properties.

PMID- 14711550
TI  - Comparison of the effect of oral and transdermal hormone therapy on fasting and
      postmethionine homocysteine levels.
AB  - OBJECTIVE: To compare the modifications on basal and post-methionine homocysteine
      (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy
      (HT). DESIGN: Prospective randomized study. SETTING: Outpatient service at
      university hospital. PATIENT(S): Twenty-four healthy postmenopausal women.
      INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and
      140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2)
      and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of
      Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations.
      RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2]
      micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index
      of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032;
      0.093] micromol/L) was observed. Modifications were similar in the transdermal
      and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related
      linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were
      significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5;
      75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8]
      micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post
      methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces
      post-methionine Hcy and fasting Hcy when it is elevated.

PMID- 14711551
TI  - Differential reproductive efficiency associated with common apolipoprotein e
      alleles in postreproductive-aged subjects.
AB  - OBJECTIVE: To investigate the possible impact of apolipoprotein E (APOE)
      polymorphism on reproductive efficiency. DESIGN: Population study. SETTING:
      University Departments and a Laboratory of National Research Council. PATIENT(S):
      One hundred sixty healthy unrelated subjects of postreproductive age.
      INTERVENTION(S): Peripheral blood collection and questionnaire administration.
      MAIN OUTCOME MEASURE(S): Apolipoprotein E genotypes were detected after PCR
      amplification and CfoI digestion; plasma total cholesterol was assayed.
      RESULT(S): The mean number of children of e*2 allele carriers (2.4) was lower
      than that of e*3/e*3 and e*4/e*3 subjects (3.9). The trend was similar (2.8 vs.
      4.8) when the number of pregnancies was considered. Moreover, there was a clear
      inverse relationship between number of children and e*2-carrying genotype
      proportions (chi(2) for trend = 6.3). Conversely, the e*3/e*3 genotype was
      associated with the highest number of children and pregnancies (3.9 and 4.9,
      respectively), and the e*4/e*3 genotype, with intermediate values (3.7 and 4.4).
      Carriers of e*2 allele also showed the lowest levels of total cholesterol.
      CONCLUSION(S): The e*2 allele seems to be associated with the lowest reproductive
      efficiency and the e*3 allele, with the highest. The different total cholesterol
      levels associated with APOE genotypes could have an effect on steroidogenesis and
      determine as a consequence the observed differential fertility.

PMID- 14711552
TI  - Increased growth hormone response to clonidine in nonobese normoinsulinemic
      patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To assess growth hormone (GH) levels in response to acute clonidine
      stimulation in nonobese patients with polycystic ovary syndrome (PCOS) in
      comparison to patients with idiopathic hirsutism (IH) and normal women without
      hirsutism. DESIGN: Cross-sectional study. Outpatient clinic, Porto Alegre,
      Brazil. PATIENT(S): Fourteen patients with PCOS, 11 women with IH, and 10 age-
      and weight-matched normal women without hirsutism were studied. All subjects
      presented normal body mass index (<25 kg/m(2)) and insulin levels (<25
      microIU/mL). INTERVENTION(S): Growth hormone levels were assessed in all patients
      before and 30, 60, 90, and 120 minutes after oral administration of 0.3 mg of
      clonidine. MAIN OUTCOME MEASURE(S): Growth hormone levels before and after
      clonidine administration. RESULT(S): Delta GH and GH levels at 30, 60, and 120
      minutes were significantly higher in the PCOS group than in the IH and control
      groups. CONCLUSION(S): The greater GH response to clonidine in nonobese
      normoinsulinemic PCOS patients observed in this study suggests a dysregulation in
      GH secretion in these patients. Further studies are required to elucidate the
      role of GH in the pathogenesis of PCOS and to investigate the existence of an
      association between androgens, IGF-I, and GH modulation in PCOS.

PMID- 14711553
TI  - Metformin administration modulates and restores luteinizing hormone spontaneous
      episodic secretion and ovarian function in nonobese patients with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To evaluate the effects of metformin administration on spontaneous LH
      episodic release in a group of nonobese polycystic ovary (PCOS) patients. DESIGN:
      Controlled clinical study. SETTING: PCOS patients in a clinical research
      environment. PATIENT(S): Twenty nonobese PCOS patients were enrolled after
      informed consent. INTERVENTION(S): All patients underwent hormonal evaluations
      and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the
      sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations
      and Ferriman-Gallwey scoring were also performed. MAIN OUTCOME MEASURE(S):
      Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy
      progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide
      concentrations. RESULT(S): After 6 months of metformin administration, the plasma
      LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin
      sensitivity, expressed as the glucose-to-insulin ratio, was significantly
      improved under glucose load after 6 months of treatment. Spontaneous LH episodic
      release showed a significant reduction in pulse amplitude with no changes in
      pulse frequency. Menstrual cyclicity was restored in all amenorrheic and
      oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were
      significantly reduced. CONCLUSION(S): Metformin administration improves
      reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By
      acting on the ovary and restoring normal ovarian activity, metformin positively
      modulates the reproductive axis (namely GnRH-LH episodic release).

PMID- 14711554
TI  - Glucose action and adrenocortical biosynthesis in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine if insulin or glucose action plays a role in
      adrenocortical steroidogenesis in the polycystic ovary syndrome (PCOS). DESIGN:
      Prospective cohort study. SETTING: Academic medical center. PATIENT(S): Nine
      reproductive-aged patients with PCOS and nine age-, race-, and body mass index
      matched controls. MAIN OUTCOME MEASURE(S): Insulin-modified frequently sampled
      intravenous glucose tolerance testing and an acute 60-minute ACTH-(1-24)
      stimulation test. From the glucose tolerance test, glucose and insulin were
      measured and the insulin sensitivity index, glucose effectiveness, and acute
      insulin response to glucose were determined. Dehydroepiandrosterone sulfate
      (DHEAS) basally and 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA,
      androstenedione, and cortisol during ACTH testing at 0 and 60 minute (steroid(0)
      and steroid(60)) were determined. The net change in steroid during the ACTH test
      was calculated. RESULT(S): The insulin sensitivity index had limited correlation
      with adrenocortical variables in both groups. In patients with PCOS, glucose
      effectiveness was positively associated with DHEAS, cortisol(0), cortisol(60),
      change in cortisol, DHEA(0), DHEA(60), change in DHEA, 17-hydroxyprenenolone(60),
      change in 17-hydroxypregnenolone, DHEA(0), androstenedione(0), 17
      hydroxyprenenolone(0), 17-hydroxyprogesterone(0), 17-hydroxyprenenolone(60), and
      17-hydroxyprogesterone(60). CONCLUSION(S): Adrenocortical biosynthesis, basally
      and in response to ACTH, appears to be closely associated with glucose
      effectiveness in PCOS. A common factor determining both the effectiveness of
      glucose to control its own production or uptake and adrenocortical biosynthesis
      may be aberrant in PCOS.

PMID- 14711555
TI  - Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome
      patients with adrenal androgen excess.
AB  - OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the
      polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA
      output in response to adrenocorticotropic hormone (ACTH), and that this
      abnormality is due to an identifiable alteration in the biosynthesis of AAs.
      DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary
      care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9)
      AA excess and controls (n = 12) without hyperandrogenism, matched for age and
      body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients.
      MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS),
      total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH
      stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17
      hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP),
      dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured.
      Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta
      hydroxysteroid dehydrogenase were estimated from product to precursor ratio,
      using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA
      excess, PCOS patients with AA excess demonstrated significantly greater levels of
      DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher
      activity of delta(5)17-OH, compared with PCOS patients without AA excess.
      CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater
      delta(5)17-OH activity in response to ACTH.

PMID- 14711556
TI  - Raloxifene prevents the growth of uterine leiomyomas in premenopausal women.
AB  - OBJECTIVE: To evaluate the effects of raloxifene administration on uterine
      leiomyoma size in premenopausal women. DESIGN: Prospective, randomized, open
      label, controlled clinical trial. SETTING: Tertiary care unit, University of
      Vienna, Austria. PATIENT(S): Twenty-five premenopausal women with uterine
      leiomyomas. INTERVENTION(S): Three months of treatment with raloxifene (180 mg/d)
      or no treatment. MAIN OUTCOME MEASURE(S): Baseline to end point percent change
      difference in leiomyoma volume between the therapy and control groups. RESULT(S):
      Raloxifene treatment prevented the progression of uterine leiomyomas. Compared
      with no medical intervention, raloxifene resulted in a decrease of myoma volume.
      Raloxifene was clinically well tolerated. No significant differences were
      detected in symptoms related to leiomyomas and hormonal status. CONCLUSION(S): In
      premenopausal women, high-dose raloxifene is well tolerated and inhibits the
      growth of leiomyomas.

PMID- 14711557
TI  - Maternal life events and adverse pregnancy outcomes: lessons from the Auvergne
      ectopic pregnancy registry.
AB  - OBJECTIVE: To investigate stressful maternal life events as candidate risk
      factors for ectopic pregnancy. DESIGN: Population-based registry study. SETTING:
      Auvergne ectopic pregnancy registry (France). PATIENT(S): Women (n = 641)
      registered between 1997 and 2000. INTERVENTION(S): Standard treatment of ectopic
      pregnancy. MAIN OUTCOME MEASURE(S): Based on the Psychiatric Epidemiology Life
      Events Scale, we analyzed the nonresponse bias, the confounding effects of
      sociobehavioral factors associated with both life events and ectopic pregnancy,
      and the potential buffering effects of socio-cultural variables. A multivariate
      model was constructed to test the association between life events and ectopic
      pregnancy, adjusting for identified confounders and testing interactions.
      RESULT(S): The primary hypothesis that life events might be independent risk
      factors for ectopic pregnancy was not confirmed in this study, which nevertheless
      illustrated the numerous biases and measurement problems confronting association
      studies of life events with adverse pregnancy outcomes. CONCLUSION(S):
      Recommendations are made for future studies on life events and adverse pregnancy
      outcomes to avoid most selection, information, and confounding biases.
      Methodological improvements are needed for measurement of life events to develop
      measures that more closely consider the consequences of stress and the mechanisms
      of buffering.

PMID- 14711558
TI  - Prediction of the change in bone mineral density induced by gonadotropin
      releasing hormone agonist treatment for endometriosis.
AB  - OBJECTIVE: To observe the long-term changes in bone metabolism induced by GnRH
      agonist (GnRHa) treatment and to determine the factor that affected the change in
      bone mineral density (BMD). DESIGN: Prospective observational study. SETTING:
      Department of obstetrics and gynecology in university and general hospitals.
      PATIENT(S): Fifty women with endometriosis treated with GnRHa between 1994 and
      1996. INTERVENTION(S): Leuprolide acetate administered for 24 weeks. Bone mineral
      density measurement by dual energy x-ray absorptiometry and collection of blood
      and urine samples were conducted until 12 months of posttreatment. MAIN OUTCOME
      MEASURE(S): Spinal BMD and bone turnover markers. RESULT(S): Mean BMD percent
      changes from pretreatment were -4.9% and -3.4% at 6 months of treatment and at 12
      months of posttreatment, respectively. When the patients were divided by the
      median pretreatment deoxypyridinoline (DP) level, recovery of BMD after GnRHa
      discontinuation was slower in the Low-DP group than in the High-DP group. A
      significant positive correlation was found between the pretreatment DP level and
      the percent change in BMD at 12 months of posttreatment. No significant relation
      between BMD and the other bone turnover markers was noted. CONCLUSION(S): Bone
      mineral density changes were diverse among patients who were administered GnRHa.
      The pretreatment DP level may be the predictive factor for GnRHa-induced BMD
      change.

PMID- 14711559
TI  - Intraovarian blood flow measured with color doppler ultrasonography inversely
      correlates with vascular density in the human corpus luteum of the menstrual
      cycle.
AB  - OBJECTIVE: To evaluate the morphologic characteristics underlying the
      ultrasonographic appearance and blood flow dynamics in the human corpus luteum
      (CL) of the menstrual cycle. DESIGN: Cross-sectional study. SETTING: Umea
      University Hospital, Umea, Sweden. PATIENT(S): Twenty-six otherwise healthy women
      with proven fertility and a history of regular menstrual cycles, scheduled for
      elective hysterectomy or tubal sterilization. INTERVENTION(S): An ovulatory LH
      rise in urine was established and the CL age was determined according to the day
      after the LH rise. Before surgery, a standardized ultrasonographic examination of
      the CL, including B-mode and color Doppler ultrasonography measurements, was
      performed. Upon commencing the minilaparotomy, the CL was excised and measured
      using a digital slide-caliper. The volume density (percentage of CL volume
      occupied by blood vessels) of factor VIII-related antigen immunostained
      endothelial cells was determined. MAIN OUTCOME MEASURE(S): Pulsatility index
      obtained from intraovarian blood vessels supplying the CL and volume density of
      blood vessels in CL tissue. The CL maximal and minimal outer and inner dimensions
      were measured in vivo by ultrasonography and ex vivo by a digital slide caliper.
      RESULT(S): A statistically significant decrease of blood vessel density and an
      increased resistance to blood flow, as indicated by pulsatility index, was
      established during the course of corpus luteum development. An inverse
      correlation between pulsatility index and volume density of blood vessels was
      found. A high degree of agreement between ultrasonographic and anatomic
      measurements of surgically removed CL was found. CONCLUSION(S): Transvaginal
      ultrasonography in combination with intraovarian color Doppler flow measurements
      is a simple and reliable method to evaluate the size and vascularization of the
      human CL.

PMID- 14711560
TI  - Recovery of natural fertility after grafting of cryopreserved germinative tissue
      in ewes subjected to radiotherapy.
AB  - OBJECTIVE: To recover natural fertility of ewes that were subjected to ovarian
      failure induced by radiotherapy with an autologous orthotopic graft of
      cryopreserved germinative tissue. DESIGN: Experimental surgery study. SETTING:
      University hospital unit. ANIMAL(S): Adult ewes. INTERVENTION(S): Four ewes were
      submitted to right oophorectomy and posterior dissecting and freezing of the
      germinative tissue. Afterward, they were administered radiotherapy to induce
      infertility on the remaining left ovary. Later, two of the ewes had the thawed
      fragments of the right ovary injected inside the cortex of the irradiated left
      ovary in a "sowing" procedure that eliminated the need for sutures. MAIN OUTCOME
      MEASURE(S): Recovery of fertility in ewes after transplantation of germinative
      tissue into the ovary destroyed by radiotherapy. RESULT(S): The ewes were housed
      with fertile rams. Six months following the grafting, the rams impregnated the
      transplanted ewes. More than 2 years after radiotherapy, the nongrafted (control)
      ewes have not become pregnant. CONCLUSION(S): Intracortical grafting of the
      germinative tissue circumvents the obstacle of vascular anastomosis with
      autologous ovarian implants. Patients could benefit from the subcortical grafting
      of germinative tissue in one of the ovaries, recovering fertility after
      radiotherapy treatment for malignancy.

PMID- 14711561
TI  - Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17beta
      estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa
      cells.
AB  - OBJECTIVE: To determine the effect of 17beta-E(2), levonorgestrel,
      medroxyprogesterone acetate, and norethindrone on the expression of vascular
      endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro.
      DESIGN: Prospective basic research study. SETTING: Basic research laboratory.
      PATIENT(S): None. INTERVENTION(S): Ishikawa cells were cultured in vitro. After
      24 hours' incubation in serum-free media, 1.0, 0.1, and 0.01 microM
      concentrations of E(2), levonorgestrel, medroxyprogesterone acetate, and
      norethindrone were added for a further 24 hours of incubation. MAIN OUTCOME
      MEASURE(S): Isolation and identification of VEGF isoforms 121 and 165 using
      semiquantitative polymerase chain reaction, gel electrophoresis, with beta-actin
      as an internal control. RESULT(S): Estradiol stimulated VEGF isoforms 121 and
      165. The progestins studied increased mRNA for VEGF isoforms 121 and 165 at all
      doses. Medroxyprogesterone acetate resulted in the greatest increase in both VEGF
      121 and 165 compared with norethindrone and levonorgestrel. CONCLUSION(S):
      Estradiol and progestins increased VEGF 121 and 165 isoform mRNA in Ishikawa
      cells in vitro. We hypothesize that differences in VEGF expression may be
      associated with the irregular bleeding during progestin use in clinical
      situations.

PMID- 14711562
TI  - In vitro transfection of the human vas deferens using DNA-liposome and DNA
      neutral lipid complexes.
AB  - OBJECTIVE: To transfect the human vas deferens in vitro. DESIGN: Prospective
      study, description of a procedure. SETTING: Research center and university
      hospital. PATIENT(S): Seven fertile men undergoing vasectomies or
      vasovasostomies. INTERVENTION(S): Human vas deferens pieces were transfected in
      vitro using the p-GeneGrip gene construction, which codifies for the green
      fluorescent protein (GFP). Lipofectamine or GenePorter were employed as gene
      vectors. MAIN OUTCOME MEASURE(S): After vas deferens epithelium transfection, we
      described the vas deferens foreign gene expression. Maximum transfection occurred
      in 14.7% of the vas deferens epithelial cells. After using GenePorter, we
      observed green fluorescent protein gene expression in 40% of samples, which
      occupied 9.86% of the epithelial area. After Lipofectamine treatment, transgene
      expression occurred in 33% of the samples and occupied 9.05% of the epithelial
      area. CONCLUSION(S): The human vas deferens epithelium has the potential to be
      modified by gene transfection.

PMID- 14711563
TI  - Differential in vitro actions of nitric oxide on human endometrial cell survival.
AB  - OBJECTIVE: To investigate the presence of caspase-3 and Bcl-2 concentration in
      human endometrial tissue throughout the menstrual cycle, and study the effect of
      nitric oxide (NO) on cell proliferation and apoptosis during culture. DESIGN:
      Expression of caspase-3 and Bcl-2 concentration in endometrial explants, and
      examination of L-arginine (L-Arg) effect on epithelial and stromal cell
      proliferation and apoptosis in vitro. SETTING: Prospective study.Twenty-seven
      eumenorrheic women (37 +/- 1.2 years). INTERVENTION(S): Endometrial samples were
      obtained with Pipelle suction curette from the corpus of the uterus. MAIN OUTCOME
      MEASURE(S): Apoptosis (annexin V-FITC binding), Bcl-2 concentration (ELISA),
      caspase-3 (immunohistochemistry), cell proliferation (spectrophotometric assay),
      and gene expression (RT-PCR). RESULT(S): Caspase-3 was detected by immunoassay in
      epithelial tissue throughout the menstrual cycle and in stroma during secretory
      phase. The Bcl-2 concentration was similar in endometrial homogenates obtained
      throughout the menstrual cycle, but L-Arg decreased Bcl-2 only in endometrium
      from the proliferative phase. In epithelial cells, NO increased apoptosis by 2.1
      +/- 0.2-fold, augmented mRNA expression of Bax, and reduced expression of Bcl-2
      compared with basal cultures. In stromal cells, NO increased cell proliferation
      in a dose-dependent manner, an effect that was blocked by a NO synthase
      inhibitor. CONCLUSION(S): These data indicate that NO has a differential
      regulatory function on endometrial cell survival, as indicated by the results on
      stromal cell proliferation and epithelial cell apoptosis during culture, which
      suggests paracrine interactions between both cell types.

PMID- 14711564
TI  - Regulation of matrix metalloproteinase-1 and tissue inhibitor of matrix
      metalloproteinase-1 by dichloroacetic acid in human fibroblasts from normal
      peritoneum and adhesions.
AB  - OBJECTIVE: To examine the role of stimulation of aerobic metabolism on the
      differential expression of matrix metalloproteinase-1 (MMP-1) and tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1), which are differentially
      regulated in fibroblasts isolated from normal human peritoneum and adhesions.
      DESIGN: Tissue culture study. SETTING: University research laboratory.
      PATIENT(S): Human fibroblasts cultures from normal peritoneum and adhesions that
      were exposed to dichloroacetic acid (DCA; 0 and 100 microg/mL) for 24 hours under
      normal and hypoxic conditions. MAIN OUTCOME MEASURE(S): Real-time reverse
      transcription polymerase chain reaction of MMP-1, TIMP-1, and beta-actin.
      RESULT(S): Dichloroacetic acid stimulated peritoneal fibroblast MMP-1 mRNA
      expression under normoxic conditions; this stimulation was lost during hypoxia.
      In adhesion fibroblasts, DCA increased MMP-1 mRNA expression; this effect was
      reversed by hypoxia. Expression of TIMP-1 mRNA was insignificantly increased by
      DCA in normal peritoneal and adhesion fibroblasts under normoxic conditions;
      however under hypoxic conditions, DCA reduced TIMP-1 mRNA expression from both.
      CONCLUSION(S): Regulation of metabolic activity of peritoneal cells may provide a
      target for future interventions for reduction of development of postoperative
      adhesions, particularly as it relates to healing of peritoneal sites that did not
      previously have adhesions as opposed to sites that underwent lysis of preexistent
      adhesions.

PMID- 14711565
TI  - A new follicle aspiration needle set is equally effective and as well tolerated
      as the standard needle when used in a prospective randomized trial in a large in
      vitro fertilization program.
AB  - OBJECTIVE: To compare the effectiveness and tolerability of two different 17
      gauge follicle aspiration needles used in a large in vitro fertilization (IVF)
      program. DESIGN: Prospective, randomized single blinded study. SETTING: Private
      IVF center. PATIENT(S): Three hundred women undergoing IVF were randomly
      allocated at the time of oocyte retrieval to either the study needle (n = 151;
      follicle aspiration set [FAS] set) or the standard needle (n = 149; Echotip) used
      in the practice. Patients were blinded to the needle used. INTERVENTION(S):
      Transvaginal ultrasound-guided oocyte aspiration. MAIN OUTCOME MEASURE(S): Number
      of eggs retrieved/follicles visualized, retrieval time, mean amount of blood in
      the aspirate, egg damage, patient tolerance, physician acceptability,
      implantation, and pregnancy rate. RESULT(S): No differences were found in the
      number of eggs retrieved normalized to follicles visualized. Egg damage (4% vs.
      4.2%), average blood in the aspirate (2.2 vs. 2.2), and retrieval time per egg
      (38 vs. 36 seconds) were similar with both needles. There were also no
      differences in pain or cramping scores (at 30 minutes and 24 hours after
      retrieval) or in the physicians' ratings of the two needles. The percentage of
      patients receiving an embryo transfer (ET), the implantation rate per embryo
      transfer, and the clinical pregnancy rate per embryo transfer were comparable for
      both needles. CONCLUSION(S): The FASs are equivalent.

PMID- 14711566
TI  - Preoperative leuprolide acetate combined with Interceed* optimally reduces
      uterine adhesions and fibrosis in a rabbit model.
AB  - OBJECTIVE: To determine the optimal approach to prevent adhesions comparing
      leuprolide acetate (GnRH-a), Interceed (oxidized regenerated cellulose; Johnson &
      Johnson Medical, Inc., New Brunswick, NJ), and a combination of leuprolide with
      Interceed in a rabbit uterine horn adhesion model. DESIGN: Prospective,
      randomized, blinded study. SETTING: Certified animal care facility. ANIMAL(S):
      Twenty-eight sexually mature, female New Zealand White rabbits. INTERVENTION(S):
      Animals were prospectively randomized (by number generator) to receive GnRH-a or
      saline. After 6 weeks, standard surgical manipulations were performed at three
      sites in each uterine horn by [1]. suture, [2]. unipolar cautery, and [3].
      superficial abrasion. Interceed was applied over one randomly assigned uterine
      horn only. Six weeks after surgery, uterine adhesions were assessed visually, and
      tissue fibrosis was assessed by histology. MAIN OUTCOME MEASURE(S): Presence or
      absence of adhesions and microscopic tissue fibrosis. RESULT(S): Gonadotropin
      releasing hormone agonist significantly decreased adhesions, whereas Interceed
      alone did not reduce adhesions. However, GnRH agonist plus Interceed was the most
      effective measure to reduce tissue fibrosis. CONCLUSION(S): Preoperative GnRH-a
      is more effective than Interceed in preventing surgical adhesions in the rabbit
      uterine horn. However, preoperative GnRH-a plus Interceed may provide optimal
      results in this animal model, because microscopic tissue fibrosis is minimized
      with this combination.

PMID- 14711567
TI  - Laparoscopic management of tubal ectopic pregnancy in obese women.
AB  - OBJECTIVE: To study the surgical morbidity associated with the laparoscopic
      management of tubal ectopic pregnancy in an overweight population compared with a
      lean population. DESIGN: Retrospective study. SETTING: An academic tertiary
      referral obstetrics and gynecology center. PATIENT(S): One hundred seventeen
      patients in two groups, lean (n = 90; body mass index <or= 30) and obese (n = 27;
      body mass index >30) who had pathology-confirmed tubal ectopic pregnancies that
      were managed laparoscopically. Each group was subdivided into a laparoscopically
      managed group and a group in which laparoscopy was converted to laparotomy.
      INTERVENTION(S): None. Operative time, blood loss, and complications of
      laparoscopic surgery as well as causes of conversion from laparoscopy to
      laparotomy, in obese compared with lean women, with ectopic pregnancy. RESULT(S):
      There was no significant difference in gestational age; beta-hCG level; or
      history of previous surgeries, ectopic pregnancy, pelvic inflammatory disease, or
      endometriosis or in any of the studied outcomes (conversion rate, blood loss, and
      operative time) between the lean and obese groups or their respective subgroups
      except for operative time between obese women who underwent laparotomy, which was
      significantly longer when compared with the case of lean women who underwent
      laparotomy. Intraoperative and postoperative complications were comparable
      between the lean and obese groups, and all complications occurred in the
      completed-laparoscopy group. CONCLUSION(S): Laparoscopic management of tubal
      ectopic pregnancy does not appear to significantly increase surgical morbidity in
      obese patients.

PMID- 14711568
TI  - Pelvic mass in a woman with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Magnetic resonance imaging and laparoscopy demonstrated the presence of a myoma
      in a woman with Rokitansky syndrome.

PMID- 14711569
TI  - Meiosis I arrest and azoospermia in an infertile male explained by failure of
      formation of a component of the synaptonemal complex.
AB  - OBJECTIVE: To characterize the early stages of meiosis in a male with unexplained
      azoospermia. DESIGN: Case report. SETTING: Case Western Reserve University and
      University Hospitals of Cleveland. PATIENT(S): A 30-year-old male with
      nonobstructive azoospermia. INTERVENTION(S): Immunostaining for components of the
      synaptonemal complex and recombination-associated proteins, fluorescence in situ
      hybridization (FISH) for specific chromosomes. MAIN OUTCOME MEASURE(S):
      Progression to and through pachytene of meiosis I in controls and in the patient.
      RESULT(S): We observed complete meiosis I arrest in the patient, associated with
      failure of formation of the mature, tripartite synaptonemal complex.
      CONCLUSION(S): Abnormalities in synaptonemal complex formation are responsible
      for a proportion of cases of unexplained male infertility.

PMID- 14711570
TI  - Consecutive cervical pregnancies.
AB  - OBJECTIVE: Report of a rare case of consecutive spontaneous cervical pregnancies.
      DESIGN: Case study. SETTING: Teaching hospital. PATIENT(S): One healthy
      nulliparous woman in the early years of her fourth decade. INTERVENTION(S): The
      first of two cervical pregnancies was treated with two doses of methotrexate and
      subsequent uterine artery embolization. The second was treated with methotrexate,
      intracervical Foley catheter placement, hysteroscopic ablation of the bleeding
      cervical bed, and replacement of the Foley catheter with gradual deflation of
      balloon. MAIN OUTCOME MEASURE(S): Recognition and successful treatment of
      cervical ectopic pregnancy. RESULT(S): Each of the two cervical pregnancies was
      successfully treated. The patient subsequently carried a spontaneous intrauterine
      pregnancy to term. CONCLUSION(S): A comprehensive MEDLINE search revealed that
      this appears to be the first reported case of recurrent spontaneous cervical
      pregnancies, and only the second known case of recurrent cervical pregnancy.
      Cervical pregnancies have generally been treated with hysterectomy because of the
      potential for massive hemorrhage. However, current treatment options permit
      effective conservative management in women who desire continued fertility. This
      case illustrates various treatment options, under different circumstances, in the
      same individual.

PMID- 14711571
TI  - A successful pregnancy after intracytoplasmic sperm injection and embryo transfer
      in a patient with endometrial cancer who was treated conservatively.
AB  - OBJECTIVE: To describe a patient with polycystic ovary syndrome (PCOS) conceiving
      with intracytoplasmic sperm injection (ICSI) and embryo transfer after
      conservative treatment of early stage endometrial cancer. DESIGN: Case report.
      SETTING: Tertiary center for assisted reproductive technologies.A 32-year-old
      woman with PCOS, primary infertility of 4 years duration, and grade 1
      endometrioid endometrial cancer. INTERVENTION(S): Assessment of myometrial
      invasion and extrauterine spread with magnetic resonance imaging (MRI) and
      explorative laparotomy. High-dose progestin treatment and ICSI and embryo
      transfer. MAIN OUTCOME MEASURE(S): Successful take-home baby and no residual
      endometrial cancer. RESULT(S): A healthy normal female infant with a birth weight
      of 1740 g was born by cesarean section at 30 weeks' gestation. No residual cancer
      was detected at the follow-up curettage performed 2 months after the delivery.
      CONCLUSION(S): Conservative uterus-preserving treatment may be considered in
      patients with early stage endometrial cancer. Assisted reproductive technologies
      may be used in such patients for immediate achievement of pregnancy.

PMID- 14711572
TI  - Pessimism and optimism.

PMID- 14711574
TI  - Pessimism and optimism.

PMID- 14711575
TI  - Protocols for posthumous fatherhood.

PMID- 14711577
TI  - Sex ratio associations: opinions, theories, and facts.

PMID- 14711580
TI  - Duration of azoospermia following anabolic steroids.

PMID- 14711583
TI  - Estrogen and progestogen therapy in postmenopausal women.

PMID- 14711584
TI  - Apoptosis of Leishmania (Leishmania) chagasi amastigotes in hamsters infected
      with visceral leishmaniasis.
AB  - Apoptosis in amastigotes from hamsters infected with visceral leishmaniasis was
      absent 30-day post-infection but appeared 90-day post-infection in the liver and
      spleen, as analysed using the TUNEL method. Necrosis was not present in these
      tissues and the nuclei of macrophages harbouring apoptotic amastigotes were
      preserved. Amastigote DNA fragmentation was demonstrated using agarose gel
      electrophoresis. DNA fragmentation was evident 90-day post-infection, coinciding
      with the occurrence of apoptosis of amastigotes in the tissues. Apoptosis of
      Leishmania amastigotes in vivo may constitute a mechanism that regulates growth
      of the parasite population during infection.

PMID- 14711585
TI  - A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic
      innovation.
AB  - The shikimate pathway is essential for survival of the apicomplexan parasites
      Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. As it is
      absent in mammals it is a promising therapeutic target. Herein, we describe the
      genes encoding the shikimate pathway enzymes in T. gondii. The molecular
      arrangement and phylogeny of the proteins suggests homology with the eukaryotic
      fungal enzymes, including a pentafunctional AROM. Current rooting of the
      eukaryotic evolutionary tree infers that the fungi and apicomplexan lineages
      diverged deeply, suggesting that the arom is an ancient supergene present in
      early eukaryotes and subsequently lost or replaced in a number of lineages.

PMID- 14711586
TI  - Regulation of immunity and pathogenesis in infectious diseases by CD1d-restricted
      NKT cells.
AB  - CD1d-restricted NKT cells are emerging as an unusual lymphoid lineage with
      important immunoregulatory properties. To date, much of our understanding of the
      biology of the CD1/NKT system comes from studies that utilise non-natural
      glycolipid ligands. Recent evidence suggests that NKT cells play an important
      role in the response to pathogens, manifesting a range of functions including
      cytotoxicity, help for antibody formation and regulation of Th1/Th2
      differentiation. Infectious disease models provide appropriate physiological and
      pathophysiological systems to explore the biological roles of this lineage in
      immunity and disease. Novel insights are emerging from infection models,
      particularly with respect to the nature of ligands recognised by the T cell
      receptor of NKT cells, and to the role of diverse non-T cell receptor NK
      activation and inhibitory receptors in regulation of the lineage. Such insights
      have the potential to add considerably to our understanding of the CD1/NKT cell
      system and to the immunology and pathogenesis of infectious diseases.

PMID- 14711587
TI  - Involvement of TNF in limiting liver pathology and promoting parasite survival
      during schistosome infection.
AB  - CD4(+) T cell responses and macrophage activation are essential components of
      schistosome egg-induced granuloma formation. Previous studies implicated tumour
      necrosis factor (TNF) as a potential mediator of macrophage recruitment and
      activation during schistosome infection. Here we demonstrate that signalling by
      TNF and its receptors can influence granuloma formation, but is ultimately
      dispensable for granuloma formation in this system. However, we identify a
      previously unrecognised role for TNF in limiting hepatocellular damage in
      response to schistosome eggs. Further, we show that this activity of TNF is
      independent of TNF receptors (TNFR1 and TNFR2). Taken together, these data
      suggest that additional, as yet unrecognised receptors exist for TNF and that
      these receptors are capable of mediating important pathological effects in the
      liver. Finally, we provide evidence that TNF plays an unexpected role in
      maintaining adult schistosome viability in the portal system.

PMID- 14711588
TI  - Processes leading to a spatial aggregation of Echinococcus multilocularis in its
      natural intermediate host Microtus arvalis.
AB  - The small fox tapeworm (Echinococcus multilocularis) shows a heterogeneous
      spatial distribution in the intermediate host (Microtus arvalis). To identify the
      ecological processes responsible for this heterogeneity, we developed a spatially
      explicit simulation model. The model combines individual-based (foxes, Vulpes
      vulpes) and grid-based (voles) techniques to simulate the infections in both
      intermediate and definite host. If host populations are homogeneously mixed, the
      model reproduces field data for parasite prevalence only for a limited number of
      parameter combinations. As ecological parameters inevitably vary to a certain
      degree, we discarded the homogeneous mixing model as insufficient to gain insight
      into the ecology of the fox tapeworm cycle. We analysed five different model
      scenarios, each focussing on an ecological process that might be responsible for
      the heterogeneous spatial distribution of E. mulitlocularis in the intermediate
      host. Field studies revealed that the prevalence ratio between intermediate and
      definite host remains stable over a wide range of ecological conditions. Thus, by
      varying the parameters in simulation experiments, we used the robustness of the
      agreement between field data and model output as quality criterion for the five
      scenarios. Only one of the five scenarios was found to reproduce the prevalence
      ratio over a sufficient range of parameter combinations. In the accentuated
      scenario most tapeworm eggs die due to bad environmental conditions before they
      cause infections in the intermediate host. This scenario is supported by the
      known sensitivity of tapeworm eggs to high temperatures and dry conditions. The
      identified process is likely to lead to a heterogeneous availability of infective
      eggs and thus to a clumped distribution of infected intermediate hosts. In
      conclusion, areas with humid conditions and low temperatures must be pointed out
      as high risk areas for human exposure to E. multilocularis eggs as well.

PMID- 14711589
TI  - Larval morphology, genetic divergence, and contrasting levels of host
      manipulation between forms of Pomphorhynchus laevis (Acanthocephala).
AB  - Studies on parasite species with a wide geographic and ecological range may be
      confounded by still equivocal taxonomic identification. Here, we investigated
      genetic polymorphism and behavioural changes induced in a common intermediate
      host, in two different forms of Pomphorhynchus laevis based on the morphology of
      the larval infective stage (cystacanth). A 'smooth type' (S) and a 'wrinkled
      type' (W) of cystacanth were distinguished based on their surface and shape. We
      analysed sequence divergence at both nuclear (ribosomal gene 18S rDNA, and
      ribosomal internal transcribed spacers, ITS1/ITS2) and mitochondrial (cytochrome
      c oxidase subunit 1) genes of P. laevis cystacanths and adults at various
      geographical scales. A high level of sequence divergence at ITS1, ITS2 and
      cytochrome c oxidase subunit 1 (11, 8 and 20%, respectively) was found between
      these two forms. The divergence pattern consistently discriminated two groups
      independently of geographic origin or host, and was congruent with larval
      morphology. The two forms also strongly differed in the intensity of behavioural
      change induced in their common intermediate host, Gammarus pulex, with the S-type
      parasite inducing a positive phototactism, whereas W-type infected gammarids were
      as photophylic as uninfected ones. Overall, our data strongly support the
      specific status of these two forms. We suggest that smooth cystacanths correspond
      to P. laevis, whereas wrinkled cystacanths might correspond to the previously
      described and poorly documented, Pomphorhynchus tereticollis, considered a
      synonym of P. laevis. This study also confirms the value of a joint analysis of
      internal transcribed spacers and cytochrome c oxidase subunit 1 genes to
      biogeographic studies on these species. Finally, we emphasize the importance of
      linking morphological and biological characteristics of acanthocephalan
      cystacanths to molecular data, in the study of the evolutionary ecology and
      systematics of this group.

PMID- 14711590
TI  - Are insecticide-impregnated dog collars a feasible alternative to dog culling as
      a strategy for controlling canine visceral leishmaniasis in Brazil?
AB  - In a zoonotic visceral leishmaniasis (ZVL)-endemic area in Brazil, deltamethrin
      impregnated collars (DMC) were fitted to 136 dogs for 5 months and significantly
      reduced the odds of increasing their anti-Leishmania antibody titer during this
      period by 50% (95% confidence interval 29-87%, P=0.01), as compared with a
      population of 97 uncollared dogs with pre-intervention prevalence within the same
      town. Mathematical modeling suggests that under typical Brazilian ZVL-endemic
      conditions, the epidemiological impact of community-wide DMC application should
      be greater than the currently practiced dog culling strategy, but that its impact
      will be dependent on collar coverage and loss rate. Both interventions should
      have a higher proportional impact in regions of lower endemicity, but the
      relative advantage of DMC over culling increases with transmission rate.
      Sensitivity analyses indicate that the impact of either intervention is not
      significantly affected by variation in the biology of the sandfly vector, but is
      greatly influenced by variation in dog mortality and serorecovery rates.

PMID- 14711591
TI  - The amino terminal domain of a novel WD repeat protein from Trypanosoma cruzi
      contains a non-canonical mitochondrial targeting signal.
AB  - WD (tryptophan/aspartic acid) repeat proteins perform a wide variety of functions
      in eukaryotic cells. They are characterised by the presence of a number of
      conserved repeat motifs that contribute to the beta-propeller structures which
      are the common feature of this large group of proteins. We report here the
      properties of the first characterised member of this family in the American
      trypanosome, Trypanosoma cruzi (TcBPP1). In the CL Brener clone the protein is
      482 amino acids long and is predicted to contain four WD repeat motifs, flanked
      by amino and carboxyl terminal extensions. TcBPP1 is a single copy gene present
      on a 1.0/1.6 Mb pair of homologous chromosomes in a locus that is syntenic with
      the corresponding regions of Trypanosoma brucei and Leishmania major chromosomes.
      Consistent with the proposed hybrid nature of the CL Brener clone, the proteins
      encoded by the two different alleles share only 97% identity at the amino acid
      level. To determine subcellular location, we examined transfected parasites for
      the distribution of green fluorescent protein (GFP) fused with different regions
      of TcBPP1. These studies demonstrated that a 115 amino acid peptide derived from
      the amino terminal domain of TcBPP1 is able to target GFP to the mitochondrion.
      Interestingly this region lacks a typical amino terminal presequence suggesting
      that mitochondrial import is mediated by an alternative targeting signal.

PMID- 14711592
TI  - Cryptosporidium parvum regulation of human epithelial cell gene expression.
AB  - Cryptosporidium parvum is an obligate intracellular protozoan capable of causing
      life-threatening diarrhoeal disease in immunocompromised individuals. Efforts to
      develop novel therapeutic strategies have been hampered by the lack of
      understanding of the pathogenesis of infection. To better understand the host
      response to C. parvum infection, gene expression profiles of infected human
      ileocecal adenocarcinoma cells were analysed by using Affymetrix oligonucleotide
      microarrays containing probe sets for 12,600 human genes. Statistical analysis of
      expression data from three independent experiments identified 223 genes whose
      expression was reproducibly regulated by C. parvum infection at 24 h post
      inoculation (125 up-regulated and 98 down-regulated), 13 of which were validated
      by quantitative reverse transcriptase polymerase chain reaction analysis. This
      analysis revealed the consistent up-regulation of host heat-shock genes and genes
      for pro-inflammatory chemokines IL-8, RANTES, and SCYB5. Multiple genes for host
      actin and tubulin genes were up-regulated whereas genes for actin binding
      proteins were down-regulated, confirming previous observations of host
      cytoskeleton rearrangement in response to C. parvum infection. In addition, host
      genes associated with cell proliferation and apoptosis were differentially
      regulated, reflecting the complexity of host-parasite interaction. Together, this
      study demonstrated that C. parvum infection results in significant changes in
      host biochemical pathways and provides new insights into specific biological
      processes of infectious disease caused by an intracellular protozoan parasite.

PMID- 14711593
TI  - Pharmacological characterisation of neuropeptide F (NPF)-induced effects on the
      motility of Mesocestoides corti (syn. Mesocestoides vogae) larvae.
AB  - Neuropeptide F is the most abundant neuropeptide in parasitic flatworms and is
      analogous to vertebrate neuropeptide Y. This paper examines the effects of
      neuropeptide F on tetrathyridia of the cestode Mesocestoides vogae and provides
      preliminary data on the signalling mechanisms employed. Neuropeptide F (>/=10
      microM) had profound excitatory effects on larval motility in vitro. The effects
      were insensitive to high concentrations (1 mM) of the anaesthetic procaine
      hydrochloride suggesting extraneuronal sites of action. Neuropeptide F activity
      was not significantly blocked by a FMRFamide-related peptide analog
      (GNFFRdFamide) that was found to inhibit GNFFRFamide-induced excitation
      indicating the occurrence of distinct neuropeptide F and FMRFamide-related
      peptide receptors. Larval treatment with guanosine 5'-O-(2-thiodiphosphate)
      trilithium salt prior to the addition of neuropeptide F completely abolished the
      excitatory effects indicating the involvement of G-proteins and a G-protein
      coupled receptor in neuropeptide F activity. Addition of guanosine 5'-O-(2
      thiodiphosphate) following neuropeptide F had limited inhibitory effects
      consistent with the activation of a signalling cascade by the neuropeptide. With
      respect to Ca(2+) involvement in neuropeptide F-induced excitation of M. vogae
      larvae, the L-type Ca(2+)-channel blockers verapamil and nifedipine both
      abolished neuropeptide F activity as did high Mg(+) concentrations and drugs
      which blocked sarcoplasmic reticulum Ca(2+)-activated Ca(2+)-channels (ryanodine)
      and sarcoplasmic reticulum Ca(2+) pumps (cyclopiazonic acid). Therefore, both
      extracellular and intracellular Ca(2+) is important for neuropeptide F excitation
      in M. vogae. With respect to second messengers, the protein kinase C inhibitor
      chelerythrine chloride and the adenylate cyclase inhibitor MDL-2330A both
      abolished neuropeptide F-induced excitation. The involvement of a signalling
      pathway that involves protein kinase C was further supported by the fact that
      phorbol-12-myristate-13-acetate, known to directly activate protein kinase C, had
      direct excitatory effects on larval motility. Although neuropeptide F is
      structurally analogous to neuropeptide Y, its mode-of-action in flatworms appears
      quite distinct from the common signalling mechanism seen in vertebrates.

PMID- 14711594
TI  - Analysis in Escherichia coli of Plasmodium falciparum dihydropteroate synthase
      (DHPS) alleles implicated in resistance to sulfadoxine.
AB  - Mutations in Plasmodium falciparum dihydropteroate synthase have been linked to
      resistance to the antimalarial drug, sulfadoxine, which competes with the
      dihydropteroate synthase substrate, p-aminobenzoate. In an effort to evaluate the
      role of these mutations in a simple model system, we have expressed six relevant
      alleles of the P. falciparum dihydropteroate synthase gene in Escherichia coli.
      When each construct was produced in a dihydropteroate synthase disrupted E. coli
      strain that required thymidine, the thymidine requirement was lost, indicating
      heterologous complementation had occurred. In the presence of sulfadoxine, the
      growth of the strain with the wild-type dihydropteroate synthase allele was
      inhibited while those containing each of the five mutant alleles grew, indicating
      that these mutations can confer sulfadoxine resistance in E. coli. When tested
      against twelve additional 'sulfa' drugs a variety of responses were obtained. All
      strains were resistant to sulfadiazine, but the wild-type allele conferred
      sensitivity to all other sulfa drugs. Three alleles conferred resistance to
      dapsone, a drug that is to be targetted for a new regime of malaria treatment in
      Africa. All mutant alleles remained sensitive to sulfachloropyridazine and
      sulfacetamide. These results suggest new drugs that could be tried for effective
      malaria treatment.

PMID- 14711595
TI  - Characterisation of IgG(T) serum antibody responses to two larval antigen
      complexes in horses naturally- or experimentally-infected with cyathostomins.
AB  - Cyathostomins are the most common parasitic nematodes of horses. Larval stages,
      which inhabit the intestinal wall, are particularly pathogenic and can cause
      severe colitis and colic. Despite their clinical importance, diagnostic
      techniques for the prepatent stages do not exist. A method that could estimate
      mucosal infection intensity would have a major impact on the control and
      diagnosis of cyathostominosis. Here, serum IgG(T) responses to two larval antigen
      complexes of 25 and 20 kDa were quantified in horses with experimental
      infections, natural infections and in horses that presented with clinical larval
      cyathostominosis. In experimentally-infected animals, anti-25 kDa complex IgG(T)
      levels correlated positively with field exposure and with early third stage
      larval (r(s)=0.74, P=0.015) and total mucosal parasite (r(s)=0.78, P=0.010)
      burdens. In naturally exposed horses whose parasite burdens were quantified upon
      post-mortem examination, antigen-specific IgG(T) responses were significantly
      higher in infected than in uninfected horses (P=0.0001 and 0.002, for anti-25 and
      anti-20 kDa responses, respectively). In these animals, anti-25 kDa IgG(T) levels
      correlated positively with mucosal and lumenal burdens (P<0.05). IgG(T) responses
      to the 20 kDa antigen complex correlated positively with lumenal burdens
      (P=0.0043). In cases of larval cyathostominosis, antigen-specific IgG(T) levels
      were significantly higher than in uninfected ponies (P=0.002 and 0.0035, for anti
      25 and anti-20 kDa responses, respectively). These results provide evidence that
      these two complexes contain antigens with potential as markers for prepatent
      cyathostomin infection.

PMID- 14711596
TI  - Genetic analysis of inbreeding of two strains of the parasitic nematode
      Haemonchus contortus.
AB  - Haemonchus contortus is a sheep parasitic nematode that causes severe economic
      losses. Previous studies have indicated a high degree of genetic heterogeneity,
      which is hardly affected by selection for drug resistance. As a tool for the
      analysis of the population dynamics of H. contortus and its response to drug
      resistance, we designed a strategy to study the inbreeding of a benzimidazole
      sensitive and a benzimidazole-resistant strain. After 15 generations, a
      theoretical inbreeding coefficient of 0.87 was achieved. The different stages of
      inbreeding were analysed using restriction fragment polymorphism, microsatellite
      variability and amplified fragment length polymorphism. Model-based clustering of
      the amplified fragment length polymorphism genotypes showed that the allele
      frequencies of the benzimidazole-resistant strain were stable during the last
      eight generations. In the sensitive strain a gradual shift of allele frequencies
      was observed, which led to a temporary increase of the genetic diversity around
      the eight generations.

PMID- 14711597
TI  - Inhibition of adenovirus infection by the bronchoalveolar lavage supernatant in
      vitro.
AB  - BACKGROUND: Gene transfer using the adenovirus has been discouraging, since the
      level of recombinant gene expression was always low. Non-specific and specific
      immune responses prevent infection or kill infected cells. Most of the specific
      immune responses against the adenovirus are well known and can be eluded at least
      in animal models. The non-specific immune response is not so well investigated.
      We have previously demonstrated a strong anti-adenoviral effect of
      bronchoalveolar lavage (BAL) supernatants of different patients independent of
      their content of specific anti-adenoviral immunoglobulins of the subclasses IgA,
      IgG, and IgM. In this paper we examine the influence of defensins and
      immunoglobulins within the epithelial lining fluid of the lung on the infection
      of adenovirus type 5. METHODS: Pooled BAL supernatants were separated by
      gelchromatography; IgA and IgG, respectively were removed from the BAL
      supernatants by anti-IgA- and anti-IgG affinity chromatography. RESULTS: The anti
      adenoviral capacity could be assigned to the high molecular weight portion
      including the immunoglobulin- and at a much lower degree the albumin-fractions.
      All fractions from affinity chromatography; the IgA fraction, the resulting BAL
      depleted from IgA, the IgG fraction, and the resulting BAL depleted from IgG were
      highly inhibitory on adenoviral infectivity. CONCLUSION: The main anti-adenoviral
      component in BAL is part of a high molecular weight complex, either being a large
      protein itself, or being a small peptide bound unspecifically to different bigger
      proteins. Defensins are not important factors of anti-adenoviral infectivity in
      the epithelial linig fluid of our patients.

PMID- 14711598
TI  - Hepatitis B-assocciated adult-onset Still's disease presenting with neutrophilic
      urticaria.
AB  - Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disorder
      that is characterized by quotidian fever, articular manifestations, neutrophilic
      leukocytosis, and maculopapular rash. The aetiology of the disease is unknown,
      however, an infectious cause has been suggested. Here we describe a patient in
      whom neutrophilic urticaria was the cutaneous manifestation of AOSD. In addition,
      the patient suffered from chronic hepatitis B infection that may be a potential
      trigger factor of AOSD. In patients with AOSD, serological investigations for
      detection of infection should include hepatitis serology. Further, we suggest
      that urticarial lesions may be a more common cutaneous manifestation of AOSD than
      has been recognized previously. Thus it is important to include AOSD in the
      differential diagnosis of urticaria.

PMID- 14711599
TI  - No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of
      lopinavir and efavirenz during antiretroviral treatment.
AB  - BACKGROUND: In a retrospective study of HIV patients under antiretroviral
      therapy, we investigated the influence of the MDR1 genotype (C3435T) on plasma
      levels of lopinavir (LPV) and efavirenz (EFV). METHODS: The MDR1 genotype was
      analysed from 67 patients who were treated with LPV (n = 32; mean treatment
      period 53 weeks) and/or EFV (n = 43, mean treatment period 105 weeks) between
      1999 and 2003. Plasma levels of LPV (trough levels) and EFV (12-h-levels) were
      determined every three months. Data were analysed by the Kruskal-Wallis test.
      RESULTS: There were no significant differences in the LPV and EFV plasma levels
      with respect to the MDR1 3435 genotype. CONCLUSIONS: We did not find evidence for
      an influence of the MDR1 3435 genotype on plasma levels of LPV and EFV.

PMID- 14711600
TI  - Effects of esradiol and progesterone on the proliferation of human gingival
      fibroblasts.
AB  - AIM: The aim of the in vitro study was to examine the effect of estradiol and
      progesterone on the proliferation rate of human gingival fibroblasts (HGF)
      derived from a healthy and a diabetic (type II) individual. METHODS: In the first
      experiment, cells in the logarithmic proliferative phase were incubated with
      estradiol or progesterone at concentrations of 10, 50, and 100 microg/ml for 72
      h. Beside the hormones, a glucose solution at a concentration of 200 mg/dl was
      added to the cell cultures in the second experiment in order to mimic a diabetic
      situation. The proliferation rate of the cells was determined by means of
      fluorescence activity of a redox indicator (Alamar Blue(R) Assay) added to the
      cell culture. Proliferation, expressed in relative fluorescence units (RFU), was
      determined after 24, 48, and 72 h. RESULTS: Progesterone at concentrations of 50
      and 100 microg/ml significantly (Mann-Whitney-U-Test, p<0.05) reduced cellular
      growth in both cultures. Estradiol did not have a significant effect on cellular
      growth. The effect of progesterone was slightly reduced by glucose when cells
      from the healthy individual were used and remained almost unchanged with the
      cells from the diabetic patient. CONCLUSIONS: The results of the present study
      may help to understand the role of the female sex-hormones in the development of
      gingival and periodontal diseases during pregnancy. Further research work,
      however, is needed to elucidate the cellular mechanisms leading to the effects
      observed.

PMID- 14711601
TI  - Salivary immunoglobulin A and G subclasses in HIV positive patients.
AB  - Many of the opportunistic infections in HIV are related to the mucous membranes,
      but the protection of oral mucosal compartment mediated by IgA and IgG subclasses
      in saliva is still not well documented. Therefore, the aim of this study was to
      investigate the status of salivary IgA and IgG subclass in HIV positive patients.
      Levels of IgG1, IgG2, IgG3 and IgG4 were determined by ELISA and IgA1 and IgA2 by
      radial immunodiffusion in the resting whole saliva of 33 HIV patients and 21 HIV
      seronegative healthy controls and were expressed in mg/L (IgA) and ug/L (IgG) of
      saliva. Salivary IgA2 was significantly reduced in the HIV positive patients
      (p<0.0009) when compared to the healthy controls, but no differences in salivary
      IgA1 level between HIV patients and healthy controls were found. On the other
      hand, salivary IgG1, IgG2, IgG3 and IgG4 subclasses were increased (p<0.0009) in
      HIV patients in comparison to the healthy controls. We can conclude that inspite
      of IgA2 deficiency which was found in studied HIV positive patients, mucosal
      antibody responses are quite normal and might not predispose development of oral
      opportunistic infections.

PMID- 14711602
TI  - Psychological factors in the irritable bowel syndrome.
AB  - OBJECTIVE: The role of psychological factors in the irritable bowel syndrome
      (IBS) is a matter of debate. The prevalence of psychiatric disorders is high in
      IBS patients. Positive response to antidepressant therapy and presence of family
      history of depression in IBS patients have led speculations whether this syndrome
      might be regarded as an affective spectrum disorder. In this study we tried to
      examine the possible association of IBS with affective spectrum disorders.
      METHOD: Forty IBS patients from gastroenterology outpatient clinics of a
      university hospital and state hospital, 32 controls with inflammatory bowel
      disease and 34 healthy hospital workers were included in the study. Psychiatric
      interviews were done using SCID-NP (Structured Clinical Interview for DSM-Non
      patients) and psychological factors were assessed by the SCL-90-R (Symptom
      Checklist-90-Revised), the Beck Depression Inventory, the Beck Anxiety Scale and
      the Hamilton Rating Scale for Depression. Family histories were obtained by FH
      RDC (Family History Research Diagnostic Criteria). All groups were matched for
      sociodemographic variables. RESULTS: The prevalence of psychiatric disorders and
      mood disorders was higher in the IBS group than the control groups. Also IBS
      group rated higher on anxiety and depression scales than the other groups, where
      the differences were statistically significant. Presence of positive family
      history for mood disorders was higher in the IBS group. CONCLUSION: These results
      support the hypothesis that IBS might be linked to affective spectrum disorder.
      Psychiatric assessment and therapy might be useful in the course of irritable
      bowel syndrome.

PMID- 14711603
TI  - [Fifty years ago, the double helix gave birth to molecular biology].
AB  - Fifty years ago, a paper signed by two young scientists, James Watson and Francis
      Crick, and reporting a model for DNA based on a double helix structure was
      published in the scientific review Nature in date of april 25, 1953. Although
      this model of striking simplicity and rare elegance was actually worked out in a
      few months by the two men, it was the result of quite 100 years of research aimed
      at the definition of the structure of the genetic material present in living
      organisms. The double helix was the outcome of a multidisciplinary approach
      initiated in the mid 19th century by the genetic laws of Gregor Mendel and the
      discovery of the chemical nature of the desoxyribonucleic acid by Johann
      Friedrich Miesher. The discovery of the DNA structure had been at the origin of
      major scientific progress regarding mechanisms that rule the replication and the
      expression of the genetic information. Theses researches have given birth to a
      new scientific field, molecular biology, which everyone will see very soon is
      actually part in a quasi symbiotic manner of all other biological fields dealing
      with life. The spectacular development of molecular biology during the last fifty
      years was in great part possible thanks to a concomitant enormous development of
      the different methods of investigation of the biological molecules and structure.
      The present rising of biotechnology applications is the direct consequence of the
      tremendous amount of fundamental knowledge gained during the last few decennia.
      They open very important and attractive perspectives both on medical or on socio
      economic point of views. There is no doubt that the next fifty years will be as
      fruitful as the last ones.

PMID- 14711604
TI  - [RT-PCR in clinical diagnosis].
AB  - Application fields of RT-PCR (reverse transcription-polymerase chain reaction) in
      clinical diagnosis comprises the assessment of viral load for RNA viruses and the
      analysis of gene transcription products. RT-PCR is also helpful when large genes
      have to be sequenced. Developments of quantitative approaches using real-time PCR
      recently led to a major widening of RT-PCR applications in clinical diagnosis.
      However, RT reaction is delicate due to its lack of reproducibility and to RNA
      lability and frequent contamination by DNA. In some cases additional difficulties
      come from the need to obtain a specific amplification in the presence of
      homologous sequences which might be present in higher amounts than the sequence
      of interest. These caveats have to be taken into account, when designing the RT
      protocol, and when choosing PCR primers and internal and/or external references.
      This review is aimed at helping the experimental setup of a RT-PCR based assay
      according to the objectives.

PMID- 14711605
TI  - [Antidigoxin Fab fragments and digoxin monitoring: a challenge for the
      biologist].
AB  - Following administration of anti-digoxin Fab fragments, monitoring unbound
      digoxin concentrations may help ensure appropriate dosing, and prevent
      recrudescent toxicity. Ultrafiltration by using Centrifree system and measurement
      of digoxin in the ultrafiltrate is considered as reference technique. However,
      ultrafiltration method is cumbersome, costly, and some immunoassays are affected
      by matrix differences. Another approach is to analyse the serum directly by
      digoxin immunoassays without ultrafiltering it. The validity of results obtained
      depends on the architecture of the immunoassay and the amount of Fab in the
      sample. The old radioimmunoassays and usually the other competitive immunoassays
      give inaccurate results. The fluorescence polarization immunoassay (FPIA)
      slightly underestimates the total digoxin concentrations. Total digoxin levels
      obtained at 24 hours and 48 hours after treatment permit measurement of the half
      life of digoxin Fab complexes and can be used to estimate when the patient can be
      redigitalized, if necessary. The sequential immunoassays usually overestimate the
      free digoxin concentrations. The differences observed are >25% and cannot be
      explained solely by albumin binding (normal range, 20% +/- 5%). To date,
      ultrafiltration remains the best strategy for accurate determination of digoxin
      concentrations in the presence of antidigoxin Fab fragments.

PMID- 14711606
TI  - [Bone marrow aspiration for diagnostic purposes].
AB  - Examination of bone marrow aspiration is an important tool in the diagnosis of
      haematological diseases. First attempts of bone marrow sampling took place at the
      beginning of the twentieth century. Thereafter, numerous methods were proposed
      and different materials were described. The commonly accepted sites for sampling
      are sternum and the iliac crest. We describe here a sampling procedure for each
      site. Bone marrow aspiration is a safely investigation, but not recommended for
      patients with impaired haemostasis. The physician must be aware of its side
      effects and complications which could occur. The consequence of the complications
      varies according to the type of iatrogenic injury. Prevention and rapid diagnosis
      are a crucial point in the management of bone marrow aspiration accidents. To
      avoid malpractice, the procedure should be taught by senior physicians including
      theoretical as well as practical learning. The purpose of the learning is a high
      quality of care to ensure patients the best comfort in subsequent bone marrow
      examinations, this point being particularly important in paediatrics.

PMID- 14711607
TI  - [Development of a method for determining lead blood levels with
      chronopotentiometry].
AB  - A potentiometric stripping analysis method for blood lead determination, using
      Radiometer Tracelab PSU 22, has been investigated. Hemoglobin precipitation by
      hydrochloric and perchloric acids mixture allows to obtain the same signal for
      the same lead concentrations in aqueous standards and various blood samples. Thus
      it is possible to use a time saving calibration procedure. Equilibration time
      increase improved method sensitivity and precision. The analysis time was 3
      minutes per sample. The detection limit was 0.006 microM/L. The relative standard
      deviation was 3.6% for 1.351 microM/L and 6% for 0.203 microM/L. The results of
      66 determinations obtained by this method and by graphite furnace atomic
      absorption spectrometry were compared (R=0.991). Potentiometric stripping
      analysis is less expensive and very convenient for clinical laboratories.

PMID- 14711608
TI  - [Prevalence of serologic markers in celiac disease in trisomy 21 in Tunisia].
AB  - PURPOSE: This study was aimed to investigate the prevalence of serologic markers
      of celiac disease in Tunisian patients with trisomy 21. METHODS: Twenty seven
      patients with trisomy 21 were prospectively screened by indirect
      immunofluorescence for anti-reticulin and anti-endomysium antibodies, and by an
      ELISA method for anti-gliadin and anti-transglutaminase antibodies. None of the
      27 patients had known celiac disease at the time of the study. RESULTS: Anti
      reticulin, anti-endomysium, anti-gliadin and anti-transglutaminase antibodies
      were found in respectively 11%, 11%, 18.5%, and 14.8% of cases. Only one patient
      with all serologic markers of celiac disease underwent biopsy which shows a
      villous atrophy. CONCLUSION: Anti-endomysium and anti-transglutaminase antibodies
      are good immunologic markers for the screening for celiac disease, a screening
      which is justified in patient with trisomy 21.

PMID- 14711609
TI  - [Genetic study of holoprosencephaly].
AB  - Holoprosencephaly (1/16,000 live births; 1/250 conceptuses) is a complex brain
      malformation resulting from incomplete cleavage of the prosencephalon, affecting
      both the forebrain and the face. Clinical expressivity is variable, ranging from
      a single cerebral ventricule and cyclopia to clinically unaffected carriers in
      familial dominant autosomic holoprosencephaly. The disease is genetically
      heterogeneous but additional environmental agents also contribute to the
      aetiology of holoprosencephaly. In our cohort of 143 patients, 28 heterozygous
      mutations were identified: 15 in the Sonic hedgehog gene (SHH), 6 in ZIC2, 5 in
      SIX3, and 2 in TGIF. Functional tests have been set up to validate the
      significance of SHH amino acids replacements. Novel phenotypes associated with a
      mutation have been described such as abnormalities of the pituitary gland and
      corpus callosum, colobomatous microphthalmia, choanal aperture stenosis and
      isolated cleft lip. This study confirms the great genetic heterogeneity of the
      disease, the important phenotypic variability in holoprosencephalic families, and
      the absence of evident genotype-phenotype correlations.

PMID- 14711610
TI  - [Comparison of different methods of hepatitis C virus genotyping].
AB  - In order to introduce the approach of HCV genotyping in our laboratory, a
      comparative study of 3 molecular and 1 serological methods, was conducted on 62
      HCV RNA positive sera. The molecular genotyping methods target the 5'untranslated
      (UTR) region of the virus genome and are based on an amplification of the viral
      genome, followed by partial sequencing, analyses of restriction fragment length
      polymorphisms (RFLP) or molecular hybridation (Inno LiPA, Innogenetics). The
      serological method or serotyping is based on the detection of antibodies to
      genotype specific epitopes derivated from the Non Structural (NS) 4 region of the
      viral genome (HCV 1-6 Serotyping Assay, Murex Biotech). "In house" methods,
      sequencing and RFLP, identified the genotype for 13 samples classified as non
      typables by commercial kits Inno LiPA test and HCV 1-6 Serotyping Assay. Mixed
      infections revealed, especially by Inno LiPA, could not be identified by partial
      sequencing, which seems to detect only predominant genotype. For 4 samples,
      genotyping results of the methods targeting the 5'UTR were discordant with those
      of the serotyping of the NS4 region. Commercial kits are efficient to determine
      HCV genotypes, particularly in the context of antiviral therapy and patient's
      follow-up, sequencing remains the best alternative for more complete
      characterisation of viral strains and for epidemiological investigations.

PMID- 14711611
TI  - [Pseudo-hyperkalemia and thrombocytosis].

PMID- 14711612
TI  - [Plasma determination of homocysteine on CPC Immulite 2000: comparison with
      determination on IMX Abbott].
AB  - Plasma total homocysteine is a parameter frequently included in the biological
      investigation of arterious or venous thrombotic diseases. Different techniques,
      chromatographic, enzymatic, and immunochemical, are used in the measurement of
      homocysteine. Among immunochemical methods, some are conceived to function on
      multiparametric automates, leading to a greater accessibility of the test for
      most of the clinical laboratories. In this study, we have evaluated a new
      immunoassay proposed by the DPC Company for the Immulite 2000 analyzer
      (chemiluminescence) and compared its performance against the Abbott's immunoassay
      on IMx (fluorescence polarization). The results obtained show very good general
      performance of the DPC's technique. Linearity is also excellent. The within run
      CVs are 9.9, 7.0 and 5.4% and the between run CVs are 8.2, 3.9 and 4.3%
      respectively for homocysteine levels of 4.2, 13.9 and 27.7 pmol/L. We found a
      very good correlation between DPC's and Abbott's methods (regression
      analysis:y=0.948 x + 0.05; r=0.895). The mean of differences between both methods
      is -0.55 micromol/L. On the whole, the DPC technique appeared in our experience
      as easily exchangeable, from the analytical point of view, with Abbott's
      technique.

PMID- 14711613
TI  - [Evaluation of the Granada medium used for the determination of Streptococcus
      agalactiae at the eighth month of pregnancy].
AB  - Granada medium (GM) was evaluated for the detection of group B streptococci (GBS)
      in vaginal swabs compared with the standard culture on selective blood agar (BA)
      and classical identification methods. From May to November 2002, samples from 325
      pregnant women (34 to 37 weeks of gestation) were processed and 44 of these women
      (13.5%) carried GBS. Comparatively, GM was found more sensitive than the
      selective BA (95% versus 91%) in GBS recovery. The characteristic red-orange
      colonies produced by GBS are so specific that further identification is
      unnecessary. The technique is simple and results are available after overnight
      incubation, improving the time to reporting a GBS-positive result by at least 24
      h. The inconvenience of anaerobic incubation of GM plates can be avoided when a
      cover slide is placed upon the inoculum because the same pigmentation is obtained
      under these aerobic conditions. This study confirms that the routine use of GM
      appears to be an accurate, easy and highly sensitive method of identification of
      GBS in pregnant women.

PMID- 14711614
TI  - [Drug interference with the determination of urinary proteins with pyrocatechol
      violet Upro Vitros slides].
AB  - The purpose of this study is to investigate drug's interference on proteinuria's
      determination with pyorcatechol violet (Vitros technology). Five drugs were
      selected: gelatin based vascular replacement fluids (Plasmion), deferoxamine
      (Desferal), ceftriaxone (Rocephine), ceftazidime (Fortum) and imipeneme (Tienam).
      To state precisely the role played by slide's technology, a liquid phase dosage
      was simultaneously made with pyrocatechol violet. No interference was notified
      with therapeutical range for four of them: gelatin, deferoxamine, ceftazidime and
      imipeneme. Slides technology prevents from gelatin's interference because the
      colorant is sensible to this drugs. On the other hand, positive interference was
      observed with ceftriaxone for urinary concentration upper than 0.75 g/L. This
      concentration is lower than that notified by Vitros laboratory in the technical
      data.

PMID- 14711615
TI  - [Evaluation of the heterogeneous immunoassay (ACMIA) for the measurement of blood
      cyclosporin on the Behring dimension RXL clinical chemistry analyzer].
AB  - We propose an evaluation of a new heterogeneous immunoassay of cyclosporin on RXL
      HM Dimension (Dade Behring) for therapeutic cyclosporin monitoring in whole-blood
      patients transplant. The pretreatment step is performed automatically into the
      apparatus while it is a manual step with EMIT. Linearity, intra- and inter-day
      precision, limit of quantification, precision and accuracy of dilution steps and
      stability into the equipment were studied. We realized the comparison between
      ACMIA and EMIT methods on whole-blood patients transplant recipients.
      Heterogeneous immunoassay showed a good linearity between 0 and 500 ng/mL, intra-
      and inter-day precision with coefficient of variation inferior to 7.2%. We
      observed reproducible and accurate dilutions of high concentrations (500 to 2,000
      ng/mL). The correlation with EMIT technique was correct for different type of
      transplant (n=55).

PMID- 14711616
TI  - [Report of a case of type IIa hyperlipoproteinemia with spectacular clinical
      expression].

PMID- 14711617
TI  - [Validation of a diagnostic kit for factor V Leiden mutation].
AB  - The Stagen factor V Leiden mutation is a new kit allowing to perform all steps
      necessary to identify the Leiden mutation of Factor V, from DNA extraction from
      patient's blood sample to electrophoresis of amplification products. The method
      is based on an allele specific amplification, which allows patient's genotype to
      be established in a single step. Analytical properties of the kit have been
      tested first, and revealed the robustness of the kit. In a second step, a
      prospective study of a cohort of 300 thrombophilic patients demonstrated the
      specificity and the sensitivity of the method. In additions, several controls and
      methodological ingenious processes allow to minimize the risk of human or method
      errors, making the reliability of the kit. Finally, the Stagen factor V Leiden
      mutation is easy and rapid to use in hospital or private laboratories, and is
      well-suited for small series of patients of the latter.

PMID- 14711618
TI  - [Determination of plasma troponin 1c with the Immulite Turbo Troponin I (DPC)
      method: decision limit].

PMID- 14711619
TI  - Characterization of multiple-antimicrobial-resistant salmonella serovars isolated
      from retail meats.
AB  - A total of 133 Salmonella isolates recovered from retail meats purchased in the
      United States and the People's Republic of China were assayed for antimicrobial
      susceptibility, the presence of integrons and antimicrobial resistance genes, and
      horizontal transfer of characterized antimicrobial resistance determinants via
      conjugation. Seventy-three (82%) of these Salmonella isolates were resistant to
      at least one antimicrobial agent. Resistance to the following antibiotics was
      common among the United States isolates: tetracycline (68% of the isolates were
      resistant), streptomycin (61%), sulfamethoxazole (42%), and ampicillin (29%).
      Eight Salmonella isolates (6%) were resistant to ceftriaxone. Fourteen isolates
      (11%) from the People's Republic of China were resistant to nalidixic acid and
      displayed decreased susceptibility to ciprofloxacin. A total of 19 different
      antimicrobial resistance genes were identified in 30 multidrug-resistant
      Salmonella isolates. The bla(CMY-2) gene, encoding a class A AmpC beta-lactamase,
      was detected in all 10 Salmonella isolates resistant to extended-spectrum beta
      lactams. Resistance to ampicillin was most often associated with a TEM-1 family
      beta-lactamase gene. Six aminoglycoside resistance genes, aadA1, aadA2, aacC2,
      Kn, aph(3)-IIa, and aac(3)-IVa, were commonly present in the Salmonella isolates.
      Sixteen (54%) of 30 Salmonella isolates tested had integrons ranging in size from
      0.75 to 2.7 kb. Conjugation studies demonstrated that there was plasmid-mediated
      transfer of genes encoding CMY-2 and TEM-1-like beta-lactamases. These data
      indicate that Salmonella isolates recovered from retail raw meats are commonly
      resistant to multiple antimicrobials, including those used for treating
      salmonellosis, such as ceftriaxone. Genes conferring antimicrobial resistance in
      Salmonella are often carried on integrons and plasmids and could be transmitted
      through conjugation. These mobile DNA elements have likely played an important
      role in transmission and dissemination of antimicrobial resistance determinants
      among Salmonella strains.

PMID- 14711620
TI  - Saccharomyces cerevisiae JEN1 promoter activity is inversely related to
      concentration of repressing sugar.
AB  - When carbon sources are changed, Saccharomyces cerevisiae transcriptional
      patterns drastically change. To identify genes whose transcription can be used to
      quantitatively measure sugar concentrations, we searched genomic expression
      databases for a set of genes that are highly induced during the diauxic shift,
      and we used the promoters from these genes to drive expression of green
      fluorescent protein (GFP). Certain sugars, including glucose, fructose, and
      mannose, repress the promoter of JEN1, which encodes a lactate-pyruvate
      transporter, in a dose-dependent manner. Nonrepressing carbon sources include
      galactose, raffinose, ethanol, lactate, and glycerol. JEN1 promoter activity is a
      linear function of glucose concentration when organisms are grown at a steady
      state glucose concentration below 1 g/liter. JEN1 promoter repression is specific
      to carbon source; heat or cold shock, osmotic stress, DNA damage, and nitrogen
      starvation do not significantly affect promoter activity. Activation of the JEN1
      promoter requires the Snf1 protein kinase, but multiple regulatory elements most
      likely combine to provide the linear relationship between JEN1 promoter activity
      and sugar concentration. Thus, a JEN1 promoter-reporter system appears to provide
      a good living cell biosensor for the concentration of certain sugars. The JEN1
      promoter also permits quantitative regulation of cellular functions not normally
      controlled by sugar concentrations. For example, a strain expressing FLO1 under
      control of the JEN1 promoter flocculates at a low glucose concentration.

PMID- 14711621
TI  - Identification of distinct Campylobacter lari genogroups by amplified fragment
      length polymorphism and protein electrophoretic profiles.
AB  - Campylobacter lari is a phenotypically and genotypically diverse species that
      comprises the classical nalidixic acid-resistant thermophilic campylobacters
      (NARTC) and the biochemical C. lari variants, including the urease-positive
      campylobacters (UPTC), the nalidixic acid-susceptible campylobacters (NASC), and
      the urease-producing nalidixic acid-susceptible campylobacters. To study the
      taxonomic and epidemiological relationships among strains of the C. lari
      variants, amplified fragment length polymorphism (AFLP) profiling and whole-cell
      protein profile analysis were performed with 55 C. lari strains. Great genetic
      heterogeneity in AFLP and protein profiles was observed. Numerical analysis of
      AFLP profiles and of partial protein profiles allowed discrimination of four
      distinct genogroups. AFLP cluster I included nearly homogeneous patterns for C.
      lari NARTC strains (genogroup I). UPTC strains together with non-urease-producing
      NASC strains produced highly diverse patterns and were placed in genogroup II.
      The genogroup III strains had the NASC phenotype and produced more homogeneous
      patterns. Finally, genogroup IV strains had the classical NARTC phenotype and
      produced AFLP patterns that were very distinct from those of other genogroups.
      One UPTC strain had aberrant patterns and clustered separately, which may
      indicate that there is an additional genogroup. Preliminary DNA-DNA hybridization
      experiments suggested that genogroups I and III represent a single genomic
      species and that genogroup IV represents a distinct species. The detection of
      moderate levels of DNA-DNA hybridization between a genogroup II reference strain
      and genogroup I and III reference strains highlights the need for further DNA-DNA
      hybridization experiments to clarify the taxonomic status of the former group. No
      correlation of genogroups with different sources of strains was identified. These
      data show that UPTC strains are genetically diverse and distinct from NARTC
      strains. In addition, they indicate that the classical NARTC phenotype
      encompasses at least two genogroups.

PMID- 14711622
TI  - Processing deep-sea particle-rich water samples for fluorescence in situ
      hybridization: consideration of storage effects, preservation, and sonication.
AB  - Particles are often regarded as microniches of enhanced microbial production and
      activities in the pelagic ocean and are vehicles of vertical material transport
      from the euphotic zone to the deep sea. Fluorescence in situ hybridization (FISH)
      can be a useful tool to study the microbial community structures associated with
      these particles, and thus their ecological significance, yet an appropriate
      protocol for processing deep-sea particle-rich water samples is lacking. Some
      sample processing considerations are discussed in the present study, and
      different combinations of existing procedures for preservation, size
      fractionation sequential filtration, and sonication were tested in conjunction
      with FISH. Results from this study show that water samples should be filtered and
      processed within no more than 10 to 12 h after collection, or else preservation
      is necessary. The commonly used prefiltration formaldehyde fixation was shown to
      be inadequate for the rRNA targeted by FISH. However, prefiltration formaldehyde
      fixation followed by immediate freezing and postfiltration paraformaldehyde
      fixation yielded highly consistent cell abundance estimates even after 96 days or
      potentially longer storage. Size fractionation sequential filtration and
      sonication together enhanced cell abundance estimates by severalfold. Size
      fractionation sequential filtration effectively separated particle-associated
      microbial communities from their free-living counterparts, while sonication
      detached cells from particles or aggregates for more-accurate cell counting using
      epifluorescence microscopy. Optimization in sonication time is recommended for
      different specific types of samples. These tested and optimized procedures can be
      incorporated into a FISH protocol for sampling in deep-sea particle-rich waters.

PMID- 14711623
TI  - Variable bacteriocin production in the commercial starter Lactococcus lactis
      DPC4275 is linked to the formation of the cointegrate plasmid pMRC02.
AB  - Lactococcus lactis DPC4275 is a bacteriocin-producing transconjugant of the
      industrial starter strain DPC4268. Strain DPC4275 was generated through conjugal
      transfer by mating DPC4268 with L. lactis MG1363 containing the 60-kb plasmid
      pMRC01, which encodes the genetic determinants for the lantibiotic lacticin 3147
      and for a phage resistance mechanism of the abortive infection type. The many
      significant applications of this strain prompted a genetic analysis of its
      apparently unstable bacteriocin-producing phenotype. Increased levels of lacticin
      3147 produced by DPC4275 were associated with the appearance of an 80-kb plasmid,
      designated pMRC02, which was derived from DNA originating from pMRC01 (60 kb) and
      a resident DPC4268 proteinase plasmid, pMT60 (60 kb). Indeed, pMRC02 was shown to
      be derived from the insertion of a 17-kb fragment of pMRC01, encompassing the
      lacticin 3147 operon, into pMT60. The presence of pMRC02 at a high copy number
      was found to correlate with increased levels of lacticin 3147 in DPC4275 compared
      to the wild-type containing pMRC01. Subsequent transfer of pMRC02 into the
      plasmid-free strain MG1363 by electroporation allowed a direct phenotypic
      comparison with pMRC01, also studied in the MG1363 background. Plasmid pMRC02
      displayed phage resistance similar to that by pMRC01, although it was less
      potent, as demonstrated by a larger plaque size for phage c2 infection of
      MG1363(pMRC02). While this locus is flanked by IS946 elements, the sequencing of
      pMT60-pMRC01 junction sites established that this event was unlikely to be
      insertion sequence mediated and most probably occurred by homologous
      recombination followed by deletion of most of pMRC01. This was not a random
      occurrence, as nine other transconjugants investigated were found to have the
      same junction sites. Such derivatives of commercial strains producing increased
      levels of bacteriocin could be exploited as protection cultures for food
      applications.

PMID- 14711624
TI  - Measurement of biologically available naphthalene in gas and aqueous phases by
      use of a Pseudomonas putida biosensor.
AB  - Genetically constructed microbial biosensors for measuring organic pollutants are
      mostly applied in aqueous samples. Unfortunately, the detection limit of most
      biosensors is insufficient to detect pollutants at low but environmentally
      relevant concentrations. However, organic pollutants with low levels of water
      solubility often have significant gas-water partitioning coefficients, which in
      principle makes it possible to measure such compounds in the gas rather than the
      aqueous phase. Here we describe the first use of a microbial biosensor for
      measuring organic pollutants directly in the gas phase. For this purpose, we
      reconstructed a bioluminescent Pseudomonas putida naphthalene biosensor strain to
      carry the NAH7 plasmid and a chromosomally inserted gene fusion between the sal
      promoter and the luxAB genes. Specific calibration studies were performed with
      suspended and filter-immobilized biosensor cells, in aqueous solution and in the
      gas phase. Gas phase measurements with filter-immobilized biosensor cells in
      closed flasks, with a naphthalene-contaminated aqueous phase, showed that the
      biosensor cells can measure naphthalene effectively. The biosensor cells on the
      filter responded with increasing light output proportional to the naphthalene
      concentration added to the water phase, even though only a small proportion of
      the naphthalene was present in the gas phase. In fact, the biosensor cells could
      concentrate a larger proportion of naphthalene through the gas phase than in the
      aqueous suspension, probably due to faster transport of naphthalene to the cells
      in the gas phase. This led to a 10-fold lower detectable aqueous naphthalene
      concentration (50 nM instead of 0.5 micro M). Thus, the use of bacterial
      biosensors for measuring organic pollutants in the gas phase is a valid method
      for increasing the sensitivity of these valuable biological devices.

PMID- 14711625
TI  - Structural and spectral features of selenium nanospheres produced by Se-respiring
      bacteria.
AB  - Certain anaerobic bacteria respire toxic selenium oxyanions and in doing so
      produce extracellular accumulations of elemental selenium [Se(0)]. We examined
      three physiologically and phylogenetically diverse species of selenate- and
      selenite-respiring bacteria, Sulfurospirillum barnesii, Bacillus
      selenitireducens, and Selenihalanaerobacter shriftii, for the occurrence of this
      phenomenon. When grown with selenium oxyanions as the electron acceptor, all of
      these organisms formed extracellular granules consisting of stable, uniform
      nanospheres (diameter, approximately 300 nm) of Se(0) having monoclinic
      crystalline structures. Intracellular packets of Se(0) were also noted. The
      number of intracellular Se(0) packets could be reduced by first growing cells
      with nitrate as the electron acceptor and then adding selenite ions to washed
      suspensions of the nitrate-grown cells. This resulted in the formation of
      primarily extracellular Se nanospheres. After harvesting and cleansing of
      cellular debris, we observed large differences in the optical properties (UV
      visible absorption and Raman spectra) of purified extracellular nanospheres
      produced in this manner by the three different bacterial species. The spectral
      properties in turn differed substantially from those of amorphous Se(0) formed by
      chemical oxidation of H(2)Se and of black, vitreous Se(0) formed chemically by
      reduction of selenite with ascorbate. The microbial synthesis of Se(0)
      nanospheres results in unique, complex, compacted nanostructural arrangements of
      Se atoms. These arrangements probably reflect a diversity of enzymes involved in
      the dissimilatory reduction that are subtly different in different microbes.
      Remarkably, these conditions cannot be achieved by current methods of chemical
      synthesis.

PMID- 14711626
TI  - Localization of the insertion site and pathotype determination of the locus of
      enterocyte effacement of shiga toxin-producing Escherichia coli strains.
AB  - Of 220 Shiga toxin-producing Escherichia coli (STEC) strains collected in central
      France from healthy cattle, food samples, and asymptomatic children, 12 possessed
      the eae gene included in the locus of enterocyte effacement (LEE) pathogenicity
      island. Based on gene typing, we observed 7 different eae espA espB tir
      pathotypes among the 12 STEC strains and described the new espAbetav variant. As
      previously observed, the O157 serogroup is associated with eaegamma, O26 is
      associated with eaebeta, and O103 is associated with eaeepsilon. However, the
      unexpected eaezeta allele was detected in 5 of the 12 isolates. PCR amplification
      and pulsed-field gel electrophoresis using the I-CeuI endonuclease followed by
      Southern hybridization indicated that the LEE was inserted in the vicinity of the
      selC (three isolates), pheU (two isolates), or pheV (six isolates) tRNA gene. Six
      isolates harbored two or three of these tRNA loci altered by the insertion of
      integrase genes (CP4-int and/or int-phe), suggesting the insertion of additional
      foreign DNA fragments at these sites. In spite of great genetic diversity of LEE
      pathotypes and LEE insertion sites, bovine strains harbor alleles of LEE genes
      that are frequently found in clinical STEC strains isolated from outbreaks and
      sporadic cases around the world, underscoring the potential risk of the bovine
      strains on human health.

PMID- 14711627
TI  - Rapid and specific detection of Salmonella spp. in animal feed samples by PCR
      after culture enrichment.
AB  - A PCR procedure has been developed for routine analysis of viable Salmonella spp.
      in feed samples. The objective was to develop a simple PCR-compatible enrichment
      procedure to enable DNA amplification without any sample pretreatment such as DNA
      extraction or cell lysis. PCR inhibition by 14 different feed samples and natural
      background flora was circumvented by the use of the DNA polymerase Tth. This DNA
      polymerase was found to exhibit a high level of resistance to PCR inhibitors
      present in these feed samples compared to DyNAzyme II, FastStart Taq, Platinum
      Taq, Pwo, rTth, Taq, and Tfl. The specificity of the Tth assay was confirmed by
      testing 101 Salmonella and 43 non-Salmonella strains isolated from feed and food
      samples. A sample preparation method based on culture enrichment in buffered
      peptone water and DNA amplification with Tth DNA polymerase was developed. The
      probability of detecting small numbers of salmonellae in feed, in the presence of
      natural background flora, was accurately determined and found to follow a
      logistic regression model. From this model, the probability of detecting 1 CFU
      per 25 g of feed in artificially contaminated soy samples was calculated and
      found to be 0.81. The PCR protocol was evaluated on 155 naturally contaminated
      feed samples and compared to an established culture-based method, NMKL-71. Eight
      percent of the samples were positive by PCR, compared with 3% with the
      conventional method. The reasons for the differences in sensitivity are
      discussed. Use of this method in the routine analysis of animal feed samples
      would improve safety in the food chain.

PMID- 14711628
TI  - Utilization of Escherichia coli outer-membrane endoprotease OmpT variants as
      processing enzymes for production of peptides from designer fusion proteins.
AB  - Escherichia coli outer-membrane endoprotease OmpT has suitable properties for
      processing fusion proteins to produce peptides and proteins. However, utilization
      of this protease for such production has been restricted due to its generally low
      cleavage efficiency at Arg (or Lys)-Xaa, where Xaa is a nonbasic N-terminal amino
      acid of a target polypeptide. The objective of this study was to generate a
      specific and efficient OmpT protease and to utilize it as a processing enzyme for
      producing various peptides and proteins by converting its substrate specificity.
      Since OmpT Asp(97) is proposed to interact with the P1' amino acid of its
      substrates, OmpT variants with variations at Asp(97) were constructed by
      replacing this amino acid with 19 natural amino acids to alter the cleavage
      specificity at Arg (P1)-Xaa (P1'). The variant OmpT that had a methionine at this
      position, but not the wild-type OmpT, efficiently cleaved a fusion protein
      containing the amino acid sequence -Arg-Arg-Arg-Ala-Arg downward arrow motilin,
      in which motilin is a model peptide with a phenylalanine at the N terminus. The
      OmpT variants with leucine and histidine at position 97 were useful in releasing
      human adrenocorticotropic hormone (1-24) (serine at the N terminus) and human
      calcitonin precursor (cysteine at the N terminus), respectively, from fusion
      proteins. Motilin was produced by this method and was purified up to 99.0% by two
      chromatographic steps; the yield was 160 mg/liter of culture. Our novel method in
      which the OmpT variants are used could be employed for production of various
      peptides and proteins.

PMID- 14711629
TI  - Campylobacter spp., Giardia spp., Cryptosporidium spp., noroviruses, and
      indicator organisms in surface water in southwestern Finland, 2000-2001.
AB  - A total of 139 surface water samples from seven lakes and 15 rivers in
      southwestern Finland were analyzed during five consecutive seasons from autumn
      2000 to autumn 2001 for the presence of various enteropathogens (Campylobacter
      spp., Giardia spp., Cryptosporidium spp., and noroviruses) and fecal indicators
      (thermotolerant coliforms, Escherichia coli, Clostridium perfringens, and F-RNA
      bacteriophages) and for physicochemical parameters (turbidity and temperature);
      this was the first such systematic study. Altogether, 41.0% (57 of 139) of the
      samples were positive for at least one of the pathogens; 17.3% were positive for
      Campylobacter spp. (45.8% of the positive samples contained Campylobacter jejuni,
      25.0% contained Campylobacter lari, 4.2% contained Campylobacter coli, and 25.0%
      contained Campylobacter isolates that were not identified), 13.7% were positive
      for Giardia spp., 10.1% were positive for Cryptosporidium spp., and 9.4% were
      positive for noroviruses (23.0% of the positive samples contained genogroup I and
      77.0% contained genogroup II). The samples were positive for enteropathogens
      significantly (P < 0.05) less frequently during the winter season than during the
      other sampling seasons. No significant differences in the prevalence of
      enteropathogens were found when rivers and lakes were compared. The presence of
      thermotolerant coliforms, E. coli, and C. perfringens had significant bivariate
      nonparametric Spearman's rank order correlation coefficients (P < 0.001) with
      samples that were positive for one or more of the pathogens analyzed. The absence
      of these indicators in a logistic regression model was found to have significant
      predictive value (odds ratios, 1.15 x 10(8), 7.57, and 2.74, respectively; P <
      0.05) for a sample that was negative for the pathogens analyzed. There were no
      significant correlations between counts or count levels for thermotolerant
      coliforms or E. coli or the presence of F-RNA phages and pathogens in the samples
      analyzed.

PMID- 14711630
TI  - Mur-LH, the broad-spectrum endolysin of Lactobacillus helveticus temperate
      bacteriophage phi-0303.
AB  - phi-0303 is a temperate bacteriophage isolated from Lactobacillus helveticus CNRZ
      303 strain after mitomycin C induction. In this work, the gene coding for a lytic
      protein of this bacteriophage was cloned using a library of phi-0303 in
      Escherichia coli DH5alpha. The lytic activity was detected by its expression,
      using whole cells of the sensitive strain L. helveticus CNRZ 892 as the
      substrate. The lysin gene was within a 4.1-kb DNA fragment of phi-0303 containing
      six open reading frames (ORFs) and two truncated ORFs. No sequence homology with
      holin genes was found within the cloned fragment. An integrase-encoding gene was
      also present in the fragment, but it was transcribed in a direction opposite that
      of the lysin gene. The lysin-encoding lys gene was verified by PCR amplification
      from the total phage DNA and subcloned. The lys gene is a 1,122-bp sequence
      encoding a protein of 373 amino acids (Mur-LH), whose product had a deduced
      molecular mass of 40,207 Da. Comparisons with sequences in sequence databases
      showed homology with numerous endolysins of other bacteriophages. Mur-LH was
      expressed in E. coli BL21, and by renaturing sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with L. helveticus CNRZ 892 as the substrate,
      the recombinant protein showed an apparent molecular mass of 40 kDa. The N
      terminal sequence of the protein confirmed the start codon. Hydrolysis of cell
      walls of L. helveticus CNRZ 303 by the endolysin and biochemical analysis of the
      residues produced demonstrated that Mur-LH has N-acetylmuramidase activity. Last,
      the endolysin exhibited a broad spectrum of lytic activity, as it was active on
      different species, mainly thermophilic lactobacilli but also lactococci,
      pediococci, Bacillus subtilis, Brevibacterium linens, and Enterococcus faecium.

PMID- 14711631
TI  - Genetics of zwittermicin a production by Bacillus cereus.
AB  - Zwittermicin A represents a new chemical class of antibiotic and has diverse
      biological activities, including suppression of oomycete diseases of plants and
      potentiation of the insecticidal activity of Bacillus thuringiensis. To identify
      genes involved in zwittermicin A production, we generated 4,800 transposon
      mutants of B. cereus UW101C and screened them for zwittermicin A accumulation.
      Nine mutants did not produce detectable zwittermicin A, and one mutant produced
      eightfold more than the parent strain. The DNA flanking the transposon insertions
      in six of the nine nonproducing mutants contains significant sequence similarity
      to genes involved in peptide and polyketide antibiotic biosynthesis. The mutant
      that overproduced zwittermicin A contained a transposon insertion immediately
      upstream from a gene that encodes a deduced protein that is a member of the MarR
      family of transcriptional regulators. Three genes identified by the mutant
      analysis mapped to a region that was previously shown to carry the zwittermicin A
      self-resistance gene, zmaR, and a biosynthetic gene (E. A. Stohl, J. L. Milner,
      and J. Handelsman, Gene 237:403-411, 1999). Further sequencing of this region
      revealed genes proposed to encode zwittermicin A precursor biosynthetic enzymes,
      in particular, those involved in the formation of the aminomalonyl- and
      hydroxymalonyl-acyl carrier protein intermediates. Additionally, nonribosomal
      peptide synthetase (NRPS) and polyketide synthase (PKS) homologs are present,
      suggesting that zwittermicin A is synthesized by a mixed NRPS/PKS pathway.

PMID- 14711632
TI  - Structure and characterization of flavolipids, a novel class of biosurfactants
      produced by Flavobacterium sp. strain MTN11.
AB  - Herein we report the structure and selected properties of a new class of
      biosurfactants that we have named the flavolipids. The flavolipids exhibit a
      unique polar moiety that features citric acid and two cadaverine molecules.
      Flavolipids were produced by a soil isolate, Flavobacterium sp. strain MTN11
      (accession number AY162137), during growth in mineral salts medium, with 2%
      glucose as the sole carbon and energy source. MTN11 produced a mixture of at
      least 37 flavolipids ranging from 584 to 686 in molecular weight (MW). The
      structure of the major component (23%; MW = 668) was determined to be 4-[[5-(7
      methyl-(E)-2-octenoylhydroxyamino)pentyl]amino]-2-[2-[[5-(7-methyl-(E)-2
      octenoylhydroxyamino)pentyl]amino]-2-oxoethyl]-2-hydroxy-4-oxobutanoic acid. The
      partially purified flavolipid mixture isolated from strain MTN11 exhibited a
      critical micelle concentration of 300 mg/liter and reduced surface tension to
      26.0 mN/m, indicating strong surfactant activity. The flavolipid mixture was a
      strong and stable emulsifier even at concentrations as low as 19 mg/liter. It was
      also an effective solubilizing agent, and in a biodegradation study, it enhanced
      hexadecane mineralization by two isolates, MTN11 (100-fold) and Pseudomonas
      aeruginosa ATCC 9027 (2.5-fold), over an 8-day period. The flavolipid-cadmium
      stability constant was measured to be 3.61, which is comparable to that for
      organic ligands such as oxalic acid and acetic acid. In summary, the flavolipids
      represent a new class of biosurfactants that have potential for use in a variety
      of biotechnological and industrial applications.

PMID- 14711633
TI  - Enzymatic assimilation of cyanide via pterin-dependent oxygenolytic cleavage to
      ammonia and formate in Pseudomonas fluorescens NCIMB 11764.
AB  - Utilization of cyanide as a nitrogen source by Pseudomonas fluorescens NCIMB
      11764 occurs via oxidative conversion to carbon dioxide and ammonia, with the
      latter compound satisfying the nitrogen requirement. Substrate attack is
      initiated by cyanide oxygenase (CNO), which has been shown previously to have
      properties of a pterin-dependent hydroxylase. CNO was purified 71-fold and
      catalyzed the quantitative conversion of cyanide supplied at micromolar
      concentrations (10 to 50 micro M) to formate and ammonia. The specific activity
      of the partially purified enzyme was approximately 500 mU/mg of protein. The
      pterin requirement for activity could be satisfied by supplying either the fully
      (tetrahydro) or partially (dihydro) reduced forms of various pterin compounds at
      catalytic concentrations (0.5 micro M). These compounds included, for example,
      biopterin, monapterin, and neopterin, all of which were also identified in cell
      extracts. Substrate conversion was accompanied by the consumption of 1 and 2
      molar equivalents of molecular oxygen and NADH, respectively. When coupled with
      formate dehydrogenase, the complete enzymatic system for cyanide oxidation to
      carbon dioxide and ammonia was reconstituted and displayed an overall reaction
      stoichiometry of 1:1:1 for cyanide, O(2), and NADH consumed. Cyanide was also
      attacked by CNO at a higher concentration (1 mM), but in this case formamide
      accumulated as the major reaction product (formamide/formate ratio, 0.6:0.3) and
      was not further degraded. A complex reaction mechanism involving the production
      of isocyanate as a potential CNO monooxygenation product is proposed. Subsequent
      reduction of isocyanate to formamide, whose hydrolysis occurs as a CNO-bound
      intermediate, is further envisioned. To our knowledge, this is the first report
      of enzymatic conversion of cyanide to formate and ammonia by a pterin-dependent
      oxygenative mechanism.

PMID- 14711634
TI  - Effects of polyunsaturated fatty acids in growth medium on lipid composition and
      on physicochemical surface properties of lactobacilli.
AB  - Most probiotic lactobacilli adhere to intestinal surfaces, a phenomenon
      influenced by free polyunsaturated fatty acids (PUFA). The present study
      investigated whether free linoleic acid, gamma-linolenic acid, arachidonic acid,
      alpha-linolenic acid, or docosahexaenoic acid in the growth medium alters the
      fatty acid composition of lactobacilli and their physical characteristics. The
      most abundant bacterial fatty acids identified were oleic, vaccenic, and
      dihydrosterculic acids. PUFA, especially conjugated linoleic acid (CLA) isomers
      and gamma-linolenic, eicosapentaenoic, docosahexaenoic, and alpha-linolenic
      acids, also were identified in lactobacilli. When lactobacilli were cultured in
      MRS broth supplemented with various free PUFA, the incorporation of a given PUFA
      into bacterial fatty acids was clearly observed. Moreover, PUFA supplementation
      also resulted in PUFA-dependent changes in the proportions of other fatty acids;
      major interconversions were seen in octadecanoic acids (18:1), their methylenated
      derivatives (19:cyc), and CLA. Intermittent changes in eicosapentaenoic acid
      proportions also were noted. These results were paralleled by minor changes in
      the hydrophilic or hydrophobic characteristics of lactobacilli, suggesting that
      PUFA interfere with microbial adhesion to intestinal surfaces through other
      mechanisms. In conclusion, we have demonstrated that free PUFA in the growth
      medium induce changes in bacterial fatty acids in relation to the regulation of
      the degree of fatty acid unsaturation, cyclization, and proportions of CLA and
      PUFA containing 20 to 22 carbons. The potential role of lactobacilli as
      regulators of PUFA absorption may represent another means by which probiotics
      could redirect the delicate balance of inflammatory mediators derived from PUFA
      within the inflamed intestine.

PMID- 14711635
TI  - Molecular cloning and expression in Saccharomyces cerevisiae of a laccase gene
      from the ascomycete Melanocarpus albomyces.
AB  - The lac1 gene encoding an extracellular laccase was isolated from the
      thermophilic fungus Melanocarpus albomyces. This gene has five introns, and it
      encodes a protein consisting of 623 amino acids. The deduced amino acid sequence
      of the laccase was shown to have high homology with laccases from other
      ascomycetes. In addition to removal of a putative 22-amino-acid signal sequence
      and a 28-residue propeptide, maturation of the translation product of lac1 was
      shown to involve cleavage of a C-terminal 14-amino-acid extension. M. albomyces
      lac1 cDNA was expressed in Saccharomyces cerevisiae under the inducible GAL1
      promoter. Extremely low production was obtained with the expression construct
      containing laccase cDNA with its own signal and propeptide sequences. The
      activity levels were significantly improved by replacing these sequences with the
      prepro sequence of the S. cerevisiae alpha-factor gene. The role of the C
      terminal extension in laccase production in S. cerevisiae was also studied.
      Laccase production was increased sixfold with the modified cDNA that had a stop
      codon after the native processing site at the C terminus.

PMID- 14711636
TI  - Sequence analysis of amplified DNA fragments containing the region encoding the
      putative lipase substrate-binding domain and genotyping of Aeromonas hydrophila.
AB  - DNA fragments were amplified by PCR from all tested strains of Aeromonas
      hydrophila, A. caviae, and A. sobria with primers designed based on sequence
      alignment of all lipase, phospholipase C, and phospholipase A1 genes and the
      cytotonic enterotoxin gene, all of which have been reported to have the consensus
      region of the putative lipase substrate-binding domain. All strains showed lipase
      activity, and all amplified DNA fragments contained a nucleotide sequence
      corresponding to the substrate-binding domain. Thirty-five distinct nucleotide
      sequence patterns and 15 distinct deduced amino acid sequence patterns were found
      in the amplified DNA fragments from 59 A. hydrophila strains. The deduced amino
      acid sequences of the amplified DNA fragments from A. caviae and A. sobria
      strains had distinctive amino acids, suggesting a species-specific sequence in
      each organism. Furthermore, the amino acid sequence patterns appear to differ
      between clinical and environmental isolates among A. hydrophila strains. Some
      strains whose nucleotide sequences were identical to one another in the amplified
      region showed an identical DNA fingerprinting pattern by repetitive extragenic
      palindromic sequence-PCR genotyping. These results suggest that A. hydrophila,
      and also A. caviae and A. sobria strains, have a gene encoding a protein with
      lipase activity. Homologs of the gene appear to be widely distributed in
      Aeromonas strains, probably associating with the evolutionary genetic difference
      between clinical and environmental isolates of A. hydrophila. Additionally, the
      distinctive nucleotide sequences of the genes could be attributed to the genotype
      of each strain, suggesting that their analysis may be helpful in elucidating the
      genetic heterogeneity of Aeromonas.

PMID- 14711637
TI  - Detection of Salmonella enterica serovar typhimurium by using a rapid, array
      based immunosensor.
AB  - The multianalyte array biosensor (MAAB) is a rapid analysis instrument capable of
      detecting multiple analytes simultaneously. Rapid (15-min), single-analyte
      sandwich immunoassays were developed for the detection of Salmonella enterica
      serovar Typhimurium, with a detection limit of 8 x 10(4) CFU/ml; the limit of
      detection was improved 10-fold by lengthening the assay protocol to 1 h. S.
      enterica serovar Typhimurium was also detected in the following spiked
      foodstuffs, with minimal sample preparation: sausage, cantaloupe, whole liquid
      egg, alfalfa sprouts, and chicken carcass rinse. Cross-reactivity tests were
      performed with Escherichia coli and Campylobacter jejuni. To determine whether
      the MAAB has potential as a screening tool for the diagnosis of asymptomatic
      Salmonella infection of poultry, chicken excretal samples from a private,
      noncommercial farm and from university poultry facilities were tested. While the
      private farm excreta gave rise to signals significantly above the buffer blanks,
      none of the university samples tested positive for S. enterica serovar
      Typhimurium without spiking; dose-response curves of spiked excretal samples from
      university-raised poultry gave limits of detection of 8 x 10(3) CFU/g.

PMID- 14711638
TI  - Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae,
      yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast.
AB  - The absence of alcoholic fermentation makes pyruvate decarboxylase-negative (Pdc(
      )) strains of Saccharomyces cerevisiae an interesting platform for further
      metabolic engineering of central metabolism. However, Pdc(-) S. cerevisiae
      strains have two growth defects: (i) growth on synthetic medium in glucose
      limited chemostat cultures requires the addition of small amounts of ethanol or
      acetate and (ii) even in the presence of a C(2) compound, these strains cannot
      grow in batch cultures on synthetic medium with glucose. We used two subsequent
      phenotypic selection strategies to obtain a Pdc(-) strain without these growth
      defects. An acetate-independent Pdc(-) mutant was obtained via (otherwise)
      glucose-limited chemostat cultivation by progressively lowering the acetate
      content in the feed. Transcriptome analysis did not reveal the mechanisms behind
      the C(2) independence. Further selection for glucose tolerance in shake flasks
      resulted in a Pdc(-) S. cerevisiae mutant (TAM) that could grow in batch cultures
      ( micro (max) = 0.20 h(-1)) on synthetic medium, with glucose as the sole carbon
      source. Although the exact molecular mechanisms underlying the glucose-tolerant
      phenotype were not resolved, transcriptome analysis of the TAM strain revealed
      increased transcript levels of many glucose-repressible genes relative to the
      isogenic wild type in nitrogen-limited chemostat cultures with excess glucose. In
      pH-controlled aerobic batch cultures, the TAM strain produced large amounts of
      pyruvate. By repeated glucose feeding, a pyruvate concentration of 135 g liter(
      1) was obtained, with a specific pyruvate production rate of 6 to 7 mmol g of
      biomass(-1) h(-1) during the exponential-growth phase and an overall yield of
      0.54 g of pyruvate g of glucose(-1).

PMID- 14711639
TI  - Quantitative PCR with 16S rRNA-gene-targeted species-specific primers for
      analysis of human intestinal bifidobacteria.
AB  - A highly sensitive quantitative PCR detection method has been developed and
      applied to the distribution analysis of human intestinal bifidobacteria by
      combining real-time PCR with Bifidobacterium genus- and species-specific primers.
      Real-time PCR detection of serially diluted DNA extracted from cultured
      bifidobacteria was linear for cell counts ranging from 10(6) to 10 cells per PCR
      assay. It was also found that the method was applicable to the detection of
      Bifidobacterium in feces when it was present at concentrations of >10(6) cells
      per g of feces. Concerning the distribution of Bifidobacterium species in
      intestinal flora, the Bifidobacterium adolescentis group, the Bifidobacterium
      catenulatum group, and Bifidobacterium longum were found to be the three
      predominant species by examination of DNA extracted from the feces of 46 healthy
      adults. We also examined changes in the population and composition of
      Bifidobacterium species in human intestinal flora of six healthy adults over an 8
      month period. The results showed that the composition of bifidobacterial flora
      was basically stable throughout the test period.

PMID- 14711640
TI  - Metabolism of 2,2'- and 3,3'-dihydroxybiphenyl by the biphenyl catabolic pathway
      of Comamonas testosteroni B-356.
AB  - The purpose of this investigation was to examine the capacity of the biphenyl
      catabolic enzymes of Comamonas testosteroni B-356 to metabolize
      dihydroxybiphenyls symmetrically substituted on both rings. Data show that 3,3'
      dihydroxybiphenyl is by far the preferred substrate for strain B-356. However,
      the dihydrodiol metabolite is very unstable and readily tautomerizes to a dead
      end metabolite or is dehydroxylated by elimination of water. The tautomerization
      route is the most prominent. Thus, a very small fraction of the substrate is
      converted to other hydroxylated and acidic metabolites. Although 2,2'
      dihydroxybiphenyl is a poor substrate for strain B-356 biphenyl dioxygenase,
      metabolites were produced by the biphenyl catabolic enzymes, leading to
      production of 2-hydroxybenzoic acid. Data show that the major route of metabolism
      involves, as a first step, a direct dehydroxylation of one of the ortho
      substituted carbons to yield 2,3,2'-trihydroxybiphenyl. However, other
      metabolites resulting from hydroxylation of carbons 5 and 6 of 2,2'
      dihydroxybiphenyl were also produced, leading to dead-end metabolites.

PMID- 14711641
TI  - Biodiversity among Lactobacillus helveticus strains isolated from different
      natural whey starter cultures as revealed by classification trees.
AB  - Lactobacillus helveticus is a homofermentative thermophilic lactic acid bacterium
      used extensively for manufacturing Swiss type and aged Italian cheese. In this
      study, the phenotypic and genotypic diversity of strains isolated from different
      natural dairy starter cultures used for Grana Padano, Parmigiano Reggiano, and
      Provolone cheeses was investigated by a classification tree technique. A data set
      was used that consists of 119 L. helveticus strains, each of which was studied
      for its physiological characters, as well as surface protein profiles and
      hybridization with a species-specific DNA probe. The methodology employed in this
      work allowed the strains to be grouped into terminal nodes without difficult and
      subjective interpretation. In particular, good discrimination was obtained
      between L. helveticus strains isolated, respectively, from Grana Padano and from
      Provolone natural whey starter cultures. The method used in this work allowed
      identification of the main characteristics that permit discrimination of
      biotypes. In order to understand what kind of genes could code for phenotypes of
      technological relevance, evidence that specific DNA sequences are present only in
      particular biotypes may be of great interest.

PMID- 14711643
TI  - Phylogenetic and physiological diversity of microorganisms isolated from a deep
      greenland glacier ice core.
AB  - We studied a sample from the GISP 2 (Greenland Ice Sheet Project) ice core to
      determine the diversity and survival of microorganisms trapped in the ice at
      least 120,000 years ago. Previously, we examined the phylogenetic relationships
      among 16S ribosomal DNA (rDNA) sequences in a clone library obtained by PCR
      amplification from genomic DNA extracted from anaerobic enrichments. Here we
      report the isolation of nearly 800 aerobic organisms that were grouped by
      morphology and amplified rDNA restriction analysis patterns to select isolates
      for further study. The phylogenetic analyses of 56 representative rDNA sequences
      showed that the isolates belonged to four major phylogenetic groups: the high-G+C
      gram-positives, low-G+C gram-positives, Proteobacteria, and the Cytophaga
      Flavobacterium-Bacteroides group. The most abundant and diverse isolates were
      within the high-G+C gram-positive cluster that had not been represented in the
      clone library. The Jukes-Cantor evolutionary distance matrix results suggested
      that at least 7 isolates represent new species within characterized genera and
      that 49 are different strains of known species. The isolates were further
      categorized based on the isolation conditions, temperature range for growth,
      enzyme activity, antibiotic resistance, presence of plasmids, and strain-specific
      genomic variations. A significant observation with implications for the
      development of novel and more effective cultivation methods was that preliminary
      incubation in anaerobic and aerobic liquid prior to plating on agar media greatly
      increased the recovery of CFU from the ice core sample.

PMID- 14711644
TI  - Within- and between-lake variability in the composition of bacterioplankton
      communities: investigations using multiple spatial scales.
AB  - This study examined the similarity of epilimnetic bacterial community composition
      (BCC) across several within- and among-lake spatial scales, and the environmental
      factors giving rise to similar bacterial communities in different lakes were also
      explored. Samples were collected from 13 northern and southern Wisconsin lakes
      representing gradients in lake size, productivity, dissolved organic carbon and
      humic acid contents, and pH. Hypotheses regarding patchy distribution of
      bacterial communities in lakes were tested by comparing samples collected from
      nearby (tens of meters) and distant (hundreds of meters) sampling sites in the
      same lake. BCC was characterized by using a molecular fingerprinting technique,
      automated ribosomal intergenic spacer analysis (ARISA). Overall, samples
      collected at the 10-m, 100-m, and between-lake scales differed by 13, 17, and
      75%, respectively. Variation at these last two scales was significant. The
      development of within-lake variation in BCC appeared to depend on the isolation
      of water by lake shoreline features such as bays or narrow constrictions. ARISA
      profiles from northern lakes had fewer peaks and were less similar to each other
      than were those of the southern lakes, suggesting that regional features do not
      necessarily lead to the development of similar bacterial communities. Lakes at
      similar positions on productivity and dissolved organic carbon concentration
      gradients had similar bacterial communities, and bacterial diversity was
      positively correlated with lake productivity and water temperature. Factorial
      studies taking into account these gradients, as well as regional spatial scales,
      should provide much insight into the nature of aquatic bacterial biogeography.

PMID- 14711645
TI  - Novel pathway for utilization of cyclopropanecarboxylate by Rhodococcus
      rhodochrous.
AB  - A new strain isolated from soil utilizes cyclopropanecarboxylate as the sole
      source of carbon and energy and was identified as Rhodococcus rhodochrous (H.
      Nishihara, Y. Ochi, H. Nakano, M. Ando, and T. Toraya, J. Ferment. Bioeng. 80:400
      402, 1995). A novel pathway for the utilization of cyclopropanecarboxylate, a
      highly strained compound, by this bacterium was investigated.
      Cyclopropanecarboxylate-dependent reduction of NAD(+) in cell extracts of
      cyclopropanecarboxylate-grown cells was observed. When intermediates accumulated
      in vitro in the absence of NAD(+) were trapped as hydroxamic acids by reaction
      with hydroxylamine, cyclopropanecarboxohydroxamic acid and 3
      hydroxybutyrohydroxamic acid were formed. Cyclopropanecarboxyl-coenzyme A (CoA),
      3-hydroxybutyryl-CoA, and crotonyl-CoA were oxidized with NAD(+) in cell
      extracts, whereas methacrylyl-CoA and 3-hydroxyisobutyryl-CoA were not. When both
      CoA and ATP were added, organic acids corresponding to the former three CoA
      thioesters were also oxidized in vitro by NAD(+), while methacrylate, 3
      hydroxyisobutyrate, and 2-hydroxybutyrate were not. Therefore, it was concluded
      that cyclopropanecarboxylate undergoes oxidative degradation through
      cyclopropanecarboxyl-CoA and 3-hydroxybutyryl-CoA. The enzymes catalyzing
      formation and ring opening of cyclopropanecarboxyl-CoA were shown to be
      inducible, while other enzymes involved in the degradation were constitutive.

PMID- 14711646
TI  - Comparative metabolic flux analysis of lysine-producing Corynebacterium
      glutamicum cultured on glucose or fructose.
AB  - A comprehensive approach to (13)C tracer studies, labeling measurements by gas
      chromatography-mass spectrometry, metabolite balancing, and isotopomer modeling,
      was applied for comparative metabolic network analysis of lysine-producing
      Corynebacterium glutamicum on glucose or fructose. Significantly reduced yields
      of lysine and biomass and enhanced formation of dihydroxyacetone, glycerol, and
      lactate in comparison to those for glucose resulted on fructose. Metabolic flux
      analysis revealed drastic differences in intracellular flux depending on the
      carbon source applied. On fructose, flux through the pentose phosphate pathway
      (PPP) was only 14.4% of the total substrate uptake flux and therefore markedly
      decreased compared to that for glucose (62.0%). This result is due mainly to (i)
      the predominance of phosphoenolpyruvate-dependent phosphotransferase systems for
      fructose uptake (PTS(Fructose)) (92.3%), resulting in a major entry of fructose
      via fructose 1,6-bisphosphate, and (ii) the inactivity of fructose 1,6
      bisphosphatase (0.0%). The uptake of fructose during flux via PTS(Mannose) was
      only 7.7%. In glucose-grown cells, the flux through pyruvate dehydrogenase
      (70.9%) was much less than that in fructose-grown cells (95.2%). Accordingly,
      flux through the tricarboxylic acid cycle was decreased on glucose. Normalized to
      that for glucose uptake, the supply of NADPH during flux was only 112.4% on
      fructose compared to 176.9% on glucose, which might explain the substantially
      lower lysine yield of C. glutamicum on fructose. Balancing NADPH levels even
      revealed an apparent deficiency of NADPH on fructose, which is probably overcome
      by in vivo activity of malic enzyme. Based on these results, potential targets
      could be identified for optimization of lysine production by C. glutamicum on
      fructose, involving (i) modification of flux through the two PTS for fructose
      uptake, (ii) amplification of fructose 1,6-bisphosphatase to increase flux
      through the PPP, and (iii) knockout of a not-yet-annotated gene encoding
      dihydroxyacetone phosphatase or kinase activity to suppress overflow metabolism.
      Statistical evaluation revealed high precision of the estimates of flux, so the
      observed differences for metabolic flux are clearly substrate specific.

PMID- 14711647
TI  - New molecular screening tools for analysis of free-living diazotrophs in soil.
AB  - Free-living nitrogen-fixing prokaryotes (diazotrophs) are ubiquitous in soil and
      are phylogenetically and physiologically highly diverse. Molecular methods based
      on universal PCR detection of the nifH marker gene have been successfully applied
      to describe diazotroph populations in the environment. However, the use of highly
      degenerate primers and low-stringency amplification conditions render these
      methods prone to amplification bias, while less degenerate primer sets will not
      amplify all nifH genes. We have developed a fixed-primer-site approach with six
      PCR protocols using less degenerate to nondegenerate primer sets that all amplify
      the same nifH fragment as a previously published PCR protocol for universal
      amplification. These protocols target different groups of diazotrophs and allowed
      for direct comparison of the PCR products by use of restriction fragment length
      polymorphism fingerprinting. The new protocols were optimized on DNA from 14
      reference strains and were subsequently tested with bulk DNA extracts from six
      soils. These analyses revealed that the new PCR primer sets amplified nifH
      sequences that were not detected by the universal primer set. Furthermore, they
      were better suited to distinguish between diazotroph populations in the different
      soils. Because the novel primer sets were not specific for monophyletic groups of
      diazotrophs, they do not serve as an identification tool; however, they proved
      powerful as fingerprinting tools for subsets of soil diazotroph communities.

PMID- 14711642
TI  - Multilocus sequence typing scheme for bacteria of the Bacillus cereus group.
AB  - In this study we developed a multilocus sequence typing (MLST) scheme for
      bacteria of the Bacillus cereus group. This group, which includes the species B.
      cereus, B. thuringiensis, B. weihenstephanensis, and B. anthracis, is known to be
      genetically very diverse. It is also very important because it comprises
      pathogenic organisms as well as bacteria with industrial applications. The MLST
      system was established by using 77 strains having various origins, including
      humans, animals, food, and soil. A total of 67 of these strains had been analyzed
      previously by multilocus enzyme electrophoresis, and they were selected to
      represent the genetic diversity of this group of bacteria. Primers were designed
      for conserved regions of housekeeping genes, and 330- to 504-bp internal
      fragments of seven such genes, adk, ccpA, ftsA, glpT, pyrE, recF, and sucC, were
      sequenced for all strains. The number of alleles at individual loci ranged from
      25 to 40, and a total of 53 allelic profiles or sequence types (STs) were
      distinguished. Analysis of the sequence data showed that the population structure
      of the B. cereus group is weakly clonal. In particular, all five B. anthracis
      isolates analyzed had the same ST. The MLST scheme which we developed has a high
      level of resolution and should be an excellent tool for studying the population
      structure and epidemiology of the B. cereus group.

PMID- 14711648
TI  - Generation and utilization of polyclonal antibodies to a synthetic C-terminal
      amino acid fragment of divercin V41, a class IIa bacteriocin.
AB  - Polyclonal antibodies have been generated by immunization of rabbits with a
      chemically synthesized C-terminal part of divercin V41 (DvnCt) conjugated to the
      carrier protein keyhole limpet hemocyanin (KLH). The sensitivity and reactivity
      of the DvnCt-KLH-generated antibodies were evaluated by enzyme-linked
      immunosorbent assay (ELISA) using supernatant from cultures of 13 representative
      lactic acid bacterium strains, and specificity was confirmed by Western blot
      analysis. Anti-DvnCt-KLH antibodies were able to recognize not only divercin V41
      but also enterocin P and piscicocin V1b, two other members of the class IIa
      bacteriocins. Production and activity of DvnV41 were evaluated by ELISA and
      activity tests during the growth of Carnobacterium divergens V41 in MRS medium
      containing or not containing Tween 80. Divercin V41, enterocin P, and piscicocin
      V1b were therefore purified by a single-step immunoaffinity chromatography method
      using a Sepharose matrix CNBr-activated directed binding of anti-DvnCt-KLH
      polyclonal antibodies.

PMID- 14711649
TI  - Genetic structure and population dynamics of Xanthomonas axonopodis pv. manihotis
      in Colombia from 1995 to 1999.
AB  - Restriction fragment length polymorphisms (RFLPs) were used to study the
      population genetics and temporal dynamics of the cassava bacterial pathogen
      Xanthomonas axonopodis pv. manihotis. The population dynamics were addressed by
      comparing samples collected from 1995 to 1999 from six locations, spanning four
      different edaphoclimatic zones (ECZs). Forty-five different X. axonopodis pv.
      manihotis RFLP types or haplotypes were identified between 1995 and 1999. High
      genetic diversity of the X. axonopodis pv. manihotis strains was evident within
      most of the fields sampled. In all but one site, diversity decreased over time
      within fields. Haplotype frequencies significantly differed over the years in all
      but one location. Studies of the rate of change of X. axonopodis pv. manihotis
      populations during the cropping cycle in two sites showed significant changes in
      the haplotype frequencies but not composition. However, variations in pathotype
      composition were observed from one year to the next at a single site in ECZs 1
      and 2 and new pathotypes were described after 1997 in these ECZs, thus revealing
      the dramatic change in the pathogen population structure of X. axonopodis pv.
      manihotis. Disease incidence was used to show the progress of cassava bacterial
      blight in Colombia during the 5-year period in different ecosystems. Low disease
      incidence values were correlated with low rainfall in 1997 in ECZ 1.

PMID- 14711650
TI  - Characterization of lipopolysaccharides present in settled house dust.
AB  - The 3-hydroxy fatty acids (3-OHFAs) in lipopolysaccharides (LPS) play an
      important role in determining endotoxin activity, and childhood exposure to
      endotoxin has recently been associated with reduced risk of atopic diseases. To
      characterize the 3-OHFAs in house dust (HD), we used gas chromatography-mass
      spectrometry to assay 190 HD samples. Dust from beds, bedroom floors, family
      rooms, and kitchen floors was collected as part of a birth cohort study of
      childhood asthma (study 1) and a longitudinal study of home allergen and
      endotoxin (study 2). We also measured endotoxin activity with a Limulus assay and
      computed specific activity (endotoxin activity per nanomole of LPS). Longer-chain
      (C(16:0) and C(18:0)) 3-OHFAs were predominant in HD compared with short-chain
      (C(10:0), C(12:0), and C(14:0)) acids. Endotoxin activity was positively
      correlated with short-chain 3-OHFAs in both studies. In study 2, 3-OH C(16:0) was
      negatively correlated and 3-OH C(18:0) was not correlated with endotoxin
      activity, consistent with previous findings that the Limulus assay responds
      preferentially to LPS containing short-chain 3-OHFAs. Kitchen dust contained the
      highest concentrations of 3-OH C(10:0), the highest endotoxin activities, and the
      highest specific activities (P < 0.03). Bed dust contained the largest amounts of
      long-chain 3-OHFAs, the highest concentrations of LPS, and the lowest specific
      activities. Apartments had significantly different types of LPS (P = 0.03)
      compared with single-family homes in study 2. These data suggest that the Limulus
      assay may underestimate exposure to certain types of LPS. Because nontoxic LPS
      may have immune modulating effects, analysis of 3-OHFAs may be useful in
      epidemiologic studies.

PMID- 14711651
TI  - Cell size and water permeability as determining factors for cell viability after
      freezing at different cooling rates.
AB  - This work studied the viabilities of five types of cells (two yeast cells,
      Saccharomyces cerevisiae CBS 1171 and Candida utilis; two bacterial strains,
      Escherichia coli and Lactobacillus plantarum; and one human leukemia K562 cell)
      as a function of cooling rate during freezing. The range of investigated cooling
      rates extended from 5 to 30,000 degrees C/min. Cell viability was classified into
      three ranges: (i) high viability for low cooling rates (5 to 180 degrees C/min),
      which allow cell water outflow to occur completely and do not allow any
      intracellular crystallization; (ii) low viability for rapid cooling rates (180 to
      5,000 degrees C/min), which allow the heat flow to prevail over water outflow (in
      this case, cell water crystallization would occur as water was flowing out of the
      cell); (iii) high viability for very high cooling rates (>5,000 degrees C/min),
      which allow the heat flow to be very rapid and induce intracellular
      crystallization and/or vitrification before any water outflow from the cell.
      Finally, an assumption relating cell death to the cell water crystallization as
      water is flowing out of the cell is made. In addition, this general cell behavior
      is different for each type of cell and seems to be moderated by the cell size,
      the water permeability properties, and the presence of a cell wall.

PMID- 14711652
TI  - Wolbachia transfer from Rhagoletis cerasi to Drosophila simulans: investigating
      the outcomes of host-symbiont coevolution.
AB  - Wolbachia is an endosymbiont of diverse arthropod lineages that can induce
      various alterations of host reproduction for its own benefice. Cytoplasmic
      incompatibility (CI) is the most common phenomenon, which results in embryonic
      lethality when males that bear Wolbachia are mated with females that do not. In
      the cherry fruit fly, Rhagoletis cerasi, Wolbachia seems to be responsible for
      previously reported patterns of incompatibility between populations. Here we
      report on the artificial transfer of two Wolbachia variants (wCer1 and wCer2)
      from R. cerasi into Drosophila simulans, which was performed with two major goals
      in mind: first, to isolate wCer1 from wCer2 in order to individually test their
      respective abilities to induce CI in the new host; and, second, to test the
      theoretical prediction that recent Wolbachia-host associations should be
      characterized by high levels of CI, fitness costs to the new host, and
      inefficient transmission from mothers to offspring. wCer1 was unable to develop
      in the new host, resulting in its rapid loss after successful injection, while
      wCer2 was established in the new host. Transmission rates of wCer2 were low, and
      the infection showed negative fitness effects, consistent with our prediction,
      but CI levels were unexpectedly lower in the new host. Based on these parameter
      estimates, neither wCer1 nor wCer2 could be naturally maintained in D. simulans.
      The experiment thus suggests that natural Wolbachia transfer between species
      might be restricted by many factors, should the ecological barriers be bypassed.

PMID- 14711653
TI  - Characterization of a new erm-related macrolide resistance gene present in
      probiotic strains of Bacillus clausii.
AB  - The mechanism of resistance to macrolides, lincosamides, and streptogramins B was
      studied in four Bacillus clausii strains that are mixed in a probiotic
      administered to humans for prevention of gastrointestinal side effects due to
      oral antibiotic chemotherapy and in three reference strains of B. clausii,
      DSM8716, ATCC 21536, and ATCC 21537. An 846-bp gene called erm(34), which is
      related to the erm genes conferring resistance to these antibiotics by ribosomal
      methylation, was cloned from total DNA of B. clausii DSM8716 into Escherichia
      coli. The deduced amino acid sequence presented 61% identity with that of Erm(D)
      from B. licheniformis, B. halodurans, and B. anthracis. Pulsed-field gel
      electrophoresis of total DNA digested by I-CeuI, followed by hybridization with
      an erm(34)-specific probe, indicated a chromosomal location of the gene in all B.
      clausii strains. Repeated attempts to transfer resistance to macrolides by
      conjugation from B. clausii strains to Enterococcus faecalis JH2-2, E. faecium
      HM1070, and B. subtilis UCN19 were unsuccessful.

PMID- 14711654
TI  - Nitrobenzoates and aminobenzoates are chemoattractants for Pseudomonas strains.
AB  - Three Pseudomonas strains were tested for the ability to sense and respond to
      nitrobenzoate and aminobenzoate isomers in chemotaxis assays. Pseudomonas putida
      PRS2000, a strain that grows on benzoate and 4-hydroxybenzoate by using the beta
      ketoadipate pathway, has a well-characterized beta-ketoadipate-inducible
      chemotactic response to aromatic acids. PRS2000 was chemotactic to 3- and 4
      nitrobenzoate and all three isomers of aminobenzoate when grown under conditions
      that induce the benzoate chemotactic response. P. putida TW3 and Pseudomonas sp.
      strain 4NT grow on 4-nitrotoluene and 4-nitrobenzoate by using the ortho (beta
      ketoadipate) and meta pathways, respectively, to complete the degradation of
      protocatechuate derived from 4-nitrotoluene and 4-nitrobenzoate. However, based
      on results of catechol 1,2-dioxygenase and catechol 2,3-dioxygenase assays, both
      strains were found to use the beta-ketoadipate pathway for the degradation of
      benzoate. Both strains were chemotactic to benzoate, 3- and 4-nitrobenzoate, and
      all three aminobenzoate isomers after growth with benzoate but not succinate.
      Strain TW3 was chemotactic to the same set of aromatic compounds after growth
      with 4-nitrotoluene or 4-nitrobenzoate. In contrast, strain 4NT did not respond
      to any aromatic acids when grown with 4-nitrotoluene or 4-nitrobenzoate,
      apparently because these substrates are not metabolized to the inducer (beta
      ketoadipate) of the chemotaxis system. The results suggest that strains TW3 and
      4NT have a beta-ketoadipate-inducible chemotaxis system that responds to a wide
      range of aromatic acids and is quite similar to that present in PRS2000. The
      broad specificity of this chemotaxis system works as an advantage in strains TW3
      and 4NT because it functions to detect diverse carbon sources, including 4
      nitrobenzoate.

PMID- 14711655
TI  - Census of the bacterial community of the gypsy moth larval midgut by using
      culturing and culture-independent methods.
AB  - Little is known about bacteria associated with Lepidoptera, the large group of
      mostly phytophagous insects comprising the moths and butterflies. We inventoried
      the larval midgut bacteria of a polyphagous foliivore, the gypsy moth (Lymantria
      dispar L.), whose gut is highly alkaline, by using traditional culturing and
      culture-independent methods. We also examined the effects of diet on microbial
      composition. Analysis of individual third-instar larvae revealed a high degree of
      similarity of microbial composition among insects fed on the same diet. DNA
      sequence analysis indicated that most of the PCR-amplified 16S rRNA genes belong
      to the gamma-Proteobacteria and low G+C gram-positive divisions and that the
      cultured members represented more than half of the phylotypes identified. Less
      frequently detected taxa included members of the alpha-Proteobacterium,
      Actinobacterium, and Cytophaga/Flexibacter/Bacteroides divisions. The 16S rRNA
      gene sequences from 7 of the 15 cultured organisms and 8 of the 9 sequences
      identified by PCR amplification diverged from previously reported bacterial
      sequences. The microbial composition of midguts differed substantially among
      larvae feeding on a sterilized artificial diet, aspen, larch, white oak, or
      willow. 16S rRNA analysis of cultured isolates indicated that an Enterococcus
      species and culture-independent analysis indicated that an Entbacter sp. were
      both present in all larvae, regardless of the feeding substrate; the sequences of
      these two phylotypes varied less than 1% among individual insects. These results
      provide the first comprehensive description of the microbial diversity of a
      lepidopteran midgut and demonstrate that the plant species in the diet influences
      the composition of the gut bacterial community.

PMID- 14711656
TI  - Nitrous oxide reductase (nosZ) gene fragments differ between native and
      cultivated Michigan soils.
AB  - The effect of standard agricultural management on the genetic heterogeneity of
      nitrous oxide reductase (nosZ) fragments from denitrifying prokaryotes in native
      and cultivated soil was explored. Thirty-six soil cores were composited from each
      of the two soil management conditions. nosZ gene fragments were amplified from
      triplicate samples, and PCR products were cloned and screened by restriction
      fragment length polymorphism (RFLP). The total nosZ RFLP profiles increased in
      similarity with soil sample size until triplicate 3-g samples produced visually
      identical RFLP profiles for each treatment. Large differences in total nosZ
      profiles were observed between the native and cultivated soils. The fragments
      representing major groups of clones encountered at least twice and four randomly
      selected clones with unique RFLP patterns were sequenced to verify nosZ identity.
      The sequence diversity of nosZ clones from the cultivated field was higher, and
      only eight patterns were found in clone libraries from both soils among the 182
      distinct nosZ RFLP patterns identified from the two soils. A group of clones that
      comprised 32% of all clones dominated the gene library of native soil, whereas
      many minor groups were observed in the gene library of cultivated soil. The 95%
      confidence intervals of the Chao1 nonparametric richness estimator for nosZ RFLP
      data did not overlap, indicating that the levels of species richness are
      significantly different in the two soils, the cultivated soil having higher
      diversity. Phylogenetic analysis of deduced amino acid sequences grouped the
      majority of nosZ clones into an interleaved Michigan soil cluster whose cultured
      members are alpha-Proteobacteria. Only four nosZ sequences from cultivated soil
      and one from the native soil were related to sequences found in gamma
      Proteobacteria. Sequences from the native field formed a distinct, closely
      related cluster (D(mean) = 0.16) containing 91.6% of the native clones. Clones
      from the cultivated field were more distantly related to each other (D(mean) =
      0.26), and 65% were found outside of the cluster from the native soil, further
      indicating a difference in the two communities. Overall, there appears to be a
      relationship between use and richness, diversity, and the phylogenetic position
      of nosZ sequences, indicating that agricultural use of soil caused a shift to a
      more diverse denitrifying community.

PMID- 14711657
TI  - Selection and characterization of conditionally active promoters in Lactobacillus
      plantarum, using alanine racemase as a promoter probe.
AB  - This paper describes the use of the alr gene, encoding alanine racemase, as a
      promoter-screening tool for the identification of conditional promoters in
      Lactobacillus plantarum. Random fragments of the L. plantarum WCFS1 genome were
      cloned upstream of the promoterless alr gene of Lactococcus lactis in a low-copy
      number plasmid vector. The resulting plasmid library was introduced into an L.
      plantarum Deltaalr strain (MD007), and 40,000 clones were selected. The genome
      coverage of the library was estimated to be 98%, based on nucleotide insert
      sequence and restriction analyses of the inserts of randomly selected clones. The
      library was screened for clones that were capable of complementing the D-alanine
      auxotroph phenotype of MD007 in media containing up to 10, 100, or 300 micro g of
      the competitive Alr inhibitor D-cycloserine per ml. Western blot analysis with
      polyclonal antibodies raised against lactococcal Alr revealed that the Alr
      production level required for growth increased in the presence of increasing
      concentrations of D-cycloserine, adding a quantitative factor to the primarily
      qualitative nature of the alr complementation screen. Screening of the alr
      complementation library for clones that could grow only in the presence of 0.8 M
      NaCl resulted in the identification of eight clones that upon Western blot
      analysis showed significantly higher Alr production under high-salt conditions
      than under low-salt conditions. These results established the effectiveness of
      the alanine racemase complementation screening method for the identification of
      promoters on their conditional or constitutive activity.

PMID- 14711658
TI  - Use of antibiotic susceptibility patterns and pulsed-field gel electrophoresis to
      compare historic and contemporary isolates of multi-drug-resistant Salmonella
      enterica subsp. enterica serovar Newport.
AB  - Recently, multi-drug-resistant (MDR) Salmonella enterica subspecies enterica
      serovar Newport reemerged as a public and animal health problem. The antibiotic
      resistance of 198 isolates and the pulsed-field gel electrophoresis patterns
      (PFGE) of 139 isolates were determined. Serovar Newport isolates collected
      between 1988 and 2001 were included in the study. One hundred seventy-eight
      isolates were collected from the San Joaquin valley in California and came from
      dairy cattle clinical samples, human clinical samples, bulk tank milk samples,
      fecal samples from preweaned calves, and waterways. Twenty clinical isolates from
      humans from various regions of the United States were also included in the study.
      Resistance to 18 antibiotics was determined using a disk diffusion assay. PFGE
      patterns were determined using a single enzyme (XbaI). The PFGE and antibiogram
      patterns were described using cluster analysis. Although the antibiotic
      resistance patterns of historic (1988 to 1995) and contemporary (1999 to 2001)
      isolates were similar, the contemporary isolates differed from the historic
      isolates by being resistant to cephalosporins and florfenicol and in their
      general sensitivity to kanamycin and neomycin. With few exceptions, the
      contemporary isolates clustered together and were clearly separated from the
      historic isolates. One PFGE-antibiogram cluster combination was predominant for
      the recent isolates, which were taken from human samples from all parts of the
      United States, as well as in the isolates from California, indicating a rapid
      dissemination of this phenotypic strain. The data are consistent with the
      hypothesis that the reemergence of MDR serovar Newport is not simply an
      acquisition of further antibiotic resistance genes by the historic isolates but
      reflects a different genetic lineage.

PMID- 14711659
TI  - Differential stress-induced regulation of two quinone reductases in the brown rot
      basidiomycete Gloeophyllum trabeum.
AB  - Quinone reductases (QRDs) have two important functions in the basidiomycete
      Gloeophyllum trabeum, which causes brown rot of wood. First, a QRD is required to
      generate biodegradative hydroxyl radicals via redox cycling between two G.
      trabeum extracellular metabolites, 2,5-dimethoxyhydroquinone (2,5-DMHQ) and 2,5
      dimethoxy-1,4-benzoquinone (2,5-DMBQ). Second, because 2,5-DMBQ is cytotoxic and
      2,5-DMHQ is not, a QRD is needed to maintain the intracellular pool of these
      metabolites in the reduced form. Given their importance in G. trabeum metabolism,
      QRDs could prove useful targets for new wood preservatives. We have identified
      two G. trabeum genes, each existing in two closely related, perhaps allelic
      variants, that encode QRDs in the flavodoxin family. Past work with QRD1 and
      heterologous expression of QRD2 in this study confirmed that both genes encode
      NADH-dependent, flavin-containing QRDs. Real-time reverse transcription PCR
      analyses of liquid- and wood-grown cultures showed that qrd1 expression was
      maximal during secondary metabolism, coincided with the production of 2,5-DMBQ,
      and was moderately up-regulated by chemical stressors such as quinones. By
      contrast, qrd2 expression was maximal during fungal growth when 2,5-DMBQ levels
      were low, yet was markedly up-regulated by chemical stress or heat shock. The
      total QRD activity in lysates of G. trabeum mycelium was significantly enhanced
      by induction beforehand with a cytotoxic quinone. The promoter of qrd2 contains
      likely antioxidant, xenobiotic, and heat shock elements, absent in qrd1, that
      probably explain the greater response of qrd2 transcription to stress. We
      conclude from these results that QRD1 is the enzyme G. trabeum routinely uses to
      detoxify quinones during incipient wood decay and that it could also drive the
      biodegradative quinone redox cycle. However, QRD2 assumes a more important role
      when the mycelium is stressed.

PMID- 14711660
TI  - Successful predation of filamentous bacteria by a nanoflagellate challenges
      current models of flagellate bacterivory.
AB  - Current models suggest that (i) filamentous bacteria are protected against
      predation by nanoflagellates, (ii) prey size is positively correlated with prey
      predator contact probability, and (iii) contact probability is mainly responsible
      for size-selective predation by interception-feeding flagellates. We used five
      strains of filamentous bacteria and one bacterivorous nanoflagellate, Ochromonas
      sp. strain DS, to test these assumptions. The five strains, including one
      spirochete and four Betaproteobacteria strains, were isolated by the filtration
      acclimatization method. All five strains possess flexible cells, but they differ
      in average cell length, which ranged from 4.5 to 13.7 micro m. High-resolution
      video microscopy was used to measure contact, capture, and ingestion rates, as
      well as selectivity of the flagellate feeding. Growth and feeding experiments
      with satiating and nonsatiating food conditions, as well as experiments including
      alternative well-edible prey, were performed. In contrast to predictions by
      current models, the flagellate successfully consumed all the tested filamentous
      strains. The ingestion rate was negatively correlated with bacterial length. On
      the other hand, the lengths of the filamentous bacteria were not positively
      correlated to the contact rate and capture rate but were negatively correlated to
      ingestion efficiency. In experiments including alternative nonfilamentous prey,
      the flagellates showed negative selection for filamentous bacteria, which was
      independent of food concentration and is interpreted as a passive selection. Our
      observations indicate that (i) size alone is not sufficient to define a refuge
      for filamentous bacteria from nanoflagellate predation and (ii) for the
      investigated filamentous bacteria, prey-predator contact probability could be
      more influenced by factors other than the prey size.

PMID- 14711661
TI  - Degradation of benzo[a]pyrene by Mycobacterium vanbaalenii PYR-1.
AB  - Metabolism of the environmental pollutant benzo[a]pyrene in the bacterium
      Mycobacterium vanbaalenii PYR-1 was examined. This organism initially oxidized
      benzo[a]pyrene with dioxygenases and monooxygenases at C-4,5, C-9,10, and C
      11,12. The metabolites were separated by reversed-phase high-performance liquid
      chromatography (HPLC) and characterized by UV-visible, mass, nuclear magnetic
      resonance, and circular dichroism spectral analyses. The major intermediates of
      benzo[a]pyrene metabolism that had accumulated in the culture media after 96 h of
      incubation were cis-4,5-dihydro-4,5-dihydroxybenzo[a]pyrene (benzo[a]pyrene cis
      4,5-dihydrodiol), cis-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene (benzo[a]pyrene
      cis-11,12-dihydrodiol), trans-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene
      (benzo[a]pyrene trans-11,12-dihydrodiol), 10-oxabenzo[def]chrysen-9-one, and
      hydroxymethoxy and dimethoxy derivatives of benzo[a]pyrene. The ortho-ring
      fission products 4-formylchrysene-5-carboxylic acid and 4,5-chrysene-dicarboxylic
      acid and a monocarboxylated chrysene product were formed when replacement culture
      experiments were conducted with benzo[a]pyrene cis-4,5-dihydrodiol. Chiral
      stationary-phase HPLC analysis of the dihydrodiols indicated that benzo[a]pyrene
      cis-4,5-dihydrodiol had 30% 4S,5R and 70% 4R,5S absolute stereochemistry.
      Benzo[a]pyrene cis-11,12-dihydrodiol adopted an 11S,12R conformation with 100%
      optical purity. The enantiomeric composition of benzo[a]pyrene trans-11,12
      dihydrodiol was an equal mixture of 11S,12S and 11R,12R molecules. The results of
      this study, in conjunction with those of previously reported studies, extend the
      pathways proposed for the bacterial metabolism of benzo[a]pyrene. Our study also
      provides evidence of the stereo- and regioselectivity of the oxygenases that
      catalyze the metabolism of benzo[a]pyrene in M. vanbaalenii PYR-1.

PMID- 14711662
TI  - Frequency, size, and localization of bacterial aggregates on bean leaf surfaces.
AB  - Using epifluorescence microscopy and image analysis, we have quantitatively
      described the frequency, size, and spatial distribution of bacterial aggregates
      on leaf surfaces of greenhouse-grown bean plants inoculated with the plant
      pathogenic bacterium Pseudomonas syringae pv. syringae strain B728a. Bacterial
      cells were not randomly distributed on the leaf surface but occurred in a wide
      range of cluster sizes, ranging from single cells to over 10(4) cells per
      aggregate. The average cluster size increased through time, and aggregates were
      more numerous and larger when plants were maintained under conditions of high
      relative humidity levels than under dry conditions. The large majority of
      aggregates observed were small (less than 100 cells), and aggregate sizes
      exhibited a strong right-hand-skewed frequency distribution. While large
      aggregates are not frequent on a given leaf, they often accounted for the
      majority of cells present. We observed that up to 50% of cells present on a leaf
      were located in aggregates containing 10(3) cells or more. Aggregates were
      associated with several different anatomical features of the leaf surface but not
      with stomates. Aggregates were preferentially associated with glandular trichomes
      and veins. The biological and ecological significance of aggregate formation by
      epiphytic bacteria is discussed.

PMID- 14711663
TI  - Occurrence of genes associated with enterotoxigenic and enterohemorrhagic
      Escherichia coli in agricultural waste lagoons.
AB  - The prevalence among all Escherichia coli bacteria of the LTIIa toxin gene and
      STII toxin gene, both associated with enterotoxigenic E. coli, and of three genes
      (stxI, stxII, and eaeA) associated with enterohemorrhagic E. coli was determined
      in farm waste disposal systems seasonally for 1 year. Single- and nested-PCR
      results for the number of E. coli isolates carrying each toxin gene trait were
      compared with a five-replicate most-probable-number (MPN) method. The STII and
      LTIIa toxin genes were present continuously at all farms and downstream waters
      that were tested. Nested-MPN-PCR manifested sensitivity increased over that of
      single-MPN-PCR by a factor of 32 for LTIIa, 10 for STII, and 2 for the stxI,
      stxII, and eaeA genes. The geometric mean prevalence of each toxin gene within
      the E. coli community in waste disposal site waters after nested MPN-PCR was
      1:8.5 E. coli isolates (1:8.5 E. coli) for the LTIIa toxin gene and 1:4 E. coli
      for the STII toxin gene. The geometric mean prevalence for the simultaneous
      occurrence of toxin genes stxI, stxII, and eaeA, was 1:182 E. coli. These
      findings based on total population analysis suggest that prevalence rates for
      these genes are higher than previously reported in studies based on surveys of
      single isolates. With a population-based approach, the frequency of each toxin
      gene at the corresponding disposal sites and the endemic nature of diseases on
      farms can be easily assessed, allowing farmers and public health officials to
      evaluate the risk of infection to animals or humans.

PMID- 14711664
TI  - Saturable, energy-dependent uptake of phenanthrene in aqueous phase by
      Mycobacterium sp. strain RJGII-135.
AB  - The mechanism of uptake of phenanthrene by Mycobacterium sp. strain RJGII-135, a
      polycyclic hydrocarbon-degrading bacterium, was examined with cultures grown on
      phenanthrene (induced for phenanthrene metabolism) and acetate (uninduced).
      Washed cells were suspended in aqueous solutions of [9-(14)C]phenanthrene, and
      then the cells were collected by filtration. Low-level steady-state (14)C
      concentrations in uninduced cells were achieved within the first 15 s of
      incubation. This immediate uptake did not show saturation kinetics and was not
      susceptible to inhibitors of active transport, cyanide and carbonyl cyanide m
      chlorophenylhydrazone. These results indicated that phenanthrene enters rapidly
      into the cells by passive diffusion. However, induced cells showed cumulative
      uptake over several minutes. The initial uptake rates followed saturation
      kinetics, with an apparent affinity constant (K(t)) of 26 +/- 3 nM (mean +/-
      standard deviation). Uptake of phenanthrene by induced cells was strongly
      inhibited by the inhibitors. Analysis of cell-associated (14)C-labeled compounds
      revealed that the concurrent metabolism during uptake was rapid and was not
      saturated at the substrate concentrations tested, suggesting that the saturable
      uptake observed reflects membrane transport rather than intracellular metabolism.
      These results were consistent with the presence of a saturable, energy-dependent
      mechanism for transport of phenanthrene in induced cells. Moreover, the kinetic
      data for the cumulative uptake suggested that phenanthrene is specifically bound
      by induced cells, based on its saturation with an apparent dissociation constant
      (K(d)) of 41 +/- 21 nM (mean +/- standard deviation). Given the low values of
      K(t) and K(d), Mycobacterium sp. strain RJGII-135 may use a high-affinity
      transport system(s) to take up phenanthrene from the aqueous phase.

PMID- 14711665
TI  - Overproduction of trehalose: heterologous expression of Escherichia coli
      trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase in
      Corynebacterium glutamicum.
AB  - Trehalose is a disaccharide with potential applications in the biotechnology and
      food industries. We propose a method for industrial production of trehalose,
      based on improved strains of Corynebacterium glutamicum. This paper describes the
      heterologous expression of Escherichia coli trehalose-synthesizing enzymes
      trehalose-6-phosphate synthase (OtsA) and trehalose-6-phosphate phosphatase
      (OtsB) in C. glutamicum, as well as its impact on the trehalose biosynthetic rate
      and metabolic-flux distributions, during growth in a defined culture medium. The
      new recombinant strain showed a five- to sixfold increase in the activity of
      OtsAB pathway enzymes, compared to a control strain, as well as an almost
      fourfold increase in the trehalose excretion rate during the exponential growth
      phase and a twofold increase in the final titer of trehalose. The heterologous
      expression described resulted in a reduced specific glucose uptake rate and Krebs
      cycle flux, as well as reduced pentose pathway flux, a consequence of
      downregulated glucose-6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase. The results proved the suitability of using the heterologous
      expression of Ots proteins in C. glutamicum to increase the trehalose
      biosynthetic rate and yield and suggest critical points for further improvement
      of trehalose overproduction in C. glutamicum.

PMID- 14711666
TI  - Longitudinal study of fecal shedding of Escherichia coli O157:H7 in feedlot
      cattle: predominance and persistence of specific clonal types despite massive
      cattle population turnover.
AB  - Identification of the sources and methods of transmission of Escherichia coli
      O157:H7 in feedlot cattle may facilitate the development of on-farm control
      measures for this important food-borne pathogen. The prevalence of E. coli
      O157:H7 in fecal samples of commercial feedlot cattle in 20 feedlot pens between
      April and September 2000 was determined throughout the finishing feeding period
      prior to slaughter. Using immunomagnetic separation, E. coli O157:H7 was isolated
      from 636 of 4,790 (13%) fecal samples in this study, with highest prevalence
      earliest in the feeding period. No differences were observed in the fecal or
      water trough sediment prevalence values of E. coli O157:H7 in 10 pens supplied
      with chlorinated drinking water supplies compared with nonchlorinated water pens.
      Pulsed-field gel electrophoresis of XbaI-digested bacterial DNA of the 230
      isolates obtained from eight of the pens revealed 56 unique restriction
      endonuclease digestion patterns (REDPs), although nearly 60% of the isolates
      belonged to a group of four closely related genetic subtypes that were present in
      each of the pens and throughout the sampling period. The other REDPs were
      typically transiently detected, often in single pens and on single sample dates,
      and in many cases were also closely related to the four predominant REDPs. The
      persistence and predominance of a few REDPs observed over the entire feeding
      period on this livestock operation highlight the importance of the farm
      environment, and not necessarily the incoming cattle, as a potential source or
      reservoir of E. coli O157:H7 on farms.

PMID- 14711667
TI  - Microbial anaerobic demethylation and dechlorination of chlorinated hydroquinone
      metabolites synthesized by basidiomycete fungi.
AB  - The synthesis and degradation of anthropogenic and natural organohalides are the
      basis of a global halogen cycle. Chlorinated hydroquinone metabolites (CHMs)
      synthesized by basidiomycete fungi and present in wetland and forest soil are
      constituents of that cycle. Anaerobic dehalogenating bacteria coexist with
      basidiomycete fungi in soils and sediments, but little is known about the fate of
      these halogenated fungal compounds. In sediment microcosms, the CHMs 2,3,5,6
      tetrachloro-1,4-dimethoxybenzene and 2,3,5,6-tetrachloro-4-methoxyphenol (TCMP)
      were anaerobically demethylated to tetrachlorohydroquinone (TCHQ). Subsequently,
      TCHQ was converted to trichlorohydroquinone and 2,5-dichlorohydroquinone (2,5
      DCHQ) in freshwater and estuarine enrichment cultures. Screening of several
      dehalogenating bacteria revealed that Desulfitobacterium hafniense strains DCB2
      and PCP1, Desulfitobacterium chlororespirans strain Co23, and Desulfitobacterium
      dehalogenans JW/DU1 sequentially dechlorinate TCMP to 2,3,5-trichloro-4
      methoxyphenol and 3,5-dichloro-4-methoxyphenol (3,5-DCMP). After a lag, these
      strains demethylate 3,5-DCMP to 2,6-DCHQ, which is then completely dechlorinated
      to 1,4-dihydroquinone (HQ). 2,5-DCHQ accumulated as an intermediate during the
      dechlorination of TCHQ to HQ by the TCMP-degrading desulfitobacteria. HQ
      accumulation following TCMP or TCHQ dechlorination was transient and became
      undetectable after 14 days, which suggests mineralization of the fungal
      compounds. This is the first report on the anaerobic degradation of fungal CHMs,
      and it establishes a fundamental role for microbial reductive degradation of
      natural organochlorides in the global halogen cycle.

PMID- 14711668
TI  - Analysis of dissimilatory sulfite reductase and 16S rRNA gene fragments from deep
      sea hydrothermal sites of the Suiyo Seamount, Izu-Bonin Arc, Western Pacific.
AB  - This study describes the occurrence of unique dissimilatory sulfite reductase
      (DSR) genes at a depth of 1,380 m from the deep-sea hydrothermal vent field at
      the Suiyo Seamount, Izu-Bonin Arc, Western Pacific, Japan. The DSR genes were
      obtained from microbes that grew in a catheter-type in situ growth chamber
      deployed for 3 days on a vent and from the effluent water of drilled holes at 5
      degrees C and natural vent fluids at 7 degrees C. DSR clones SUIYOdsr-A and
      SUIYOdsr-B were not closely related to cultivated species or environmental
      clones. Moreover, samples of microbial communities were examined by PCR
      denaturing gradient gel electrophoresis (DGGE) analysis of the 16S rRNA gene. The
      sequence analysis of 16S rRNA gene fragments obtained from the vent catheter
      after a 3-day incubation revealed the occurrence of bacterial DGGE bands
      affiliated with the Aquificae and gamma- and epsilon-Proteobacteria as well as
      the occurrence of archaeal phylotypes affiliated with the Thermococcales and of a
      unique archaeon sequence that clustered with "Nanoarchaeota." The DGGE bands
      obtained from drilled holes and natural vent fluids from 7 to 300 degrees C were
      affiliated with the delta-Proteobacteria, genus Thiomicrospira, and Pelodictyon.
      The dominant DGGE bands retrieved from the effluent water of casing pipes at 3
      and 4 degrees C were closely related to phylotypes obtained from the Arctic
      Ocean. Our results suggest the presence of microorganisms corresponding to a
      unique DSR lineage not detected previously from other geothermal environments.

PMID- 14711669
TI  - Growth of Escherichia coli coexpressing phosphotriesterase and
      glycerophosphodiester phosphodiesterase, using paraoxon as the sole phosphorus
      source.
AB  - Phosphotriesterases catalyze the hydrolytic detoxification of phosphotriester
      pesticides and chemical warfare nerve agents with various efficiencies. The
      directed evolution of phosphotriesterases to enhance the breakdown of poor
      substrates is desirable for the purposes of bioremediation. A limiting factor in
      the identification of phosphotriesterase mutants with increased activity is the
      ability to effectively screen large mutant libraries. To this end, we have
      investigated the possibility of coupling phosphotriesterase activity to cell
      growth by using methyl paraoxon as the sole phosphorus source. The catabolism of
      paraoxon to phosphate would occur via the stepwise enzymatic hydrolysis of
      paraoxon to dimethyl phosphate, methyl phosphate, and then phosphate. The
      Escherichia coli strain DH10B expressing the phosphotriesterase from
      Agrobacterium radiobacter P230 (OpdA) is unable to grow when paraoxon is used as
      the sole phosphorus source. Enterobacter aerogenes is an organism capable of
      growing when dimethyl phosphate is the sole phosphorus source. The enzyme
      responsible for hydrolyzing dimethyl phosphate has been previously characterized
      as a nonspecific phosphohydrolase. We isolated and characterized the genes
      encoding the phosphohydrolase operon. The operon was identified from a shotgun
      clone that enabled E. coli to grow when dimethyl phosphate is the sole phosphorus
      source. E. coli coexpressing the phosphohydrolase and OpdA grew when paraoxon was
      the sole phosphorus source. By constructing a short degradative pathway, we have
      enabled E. coli to use phosphotriesters as a sole source of phosphorus.

PMID- 14711670
TI  - Periplasmic cytochrome c3 of Desulfovibrio vulgaris is directly involved in H2
      mediated metal but not sulfate reduction.
AB  - Kinetic parameters and the role of cytochrome c(3) in sulfate, Fe(III), and U(VI)
      reduction were investigated in Desulfovibrio vulgaris Hildenborough. While
      sulfate reduction followed Michaelis-Menten kinetics (K(m) = 220 micro M), loss
      of Fe(III) and U(VI) was first-order at all concentrations tested. Initial
      reduction rates of all electron acceptors were similar for cells grown with H(2)
      and sulfate, while cultures grown using lactate and sulfate had similar rates of
      metal loss but lower sulfate reduction activities. The similarities in metal, but
      not sulfate, reduction with H(2) and lactate suggest divergent pathways.
      Respiration assays and reduced minus oxidized spectra were carried out to
      determine c-type cytochrome involvement in electron acceptor reduction. c-type
      cytochrome oxidation was immediate with Fe(III) and U(VI) in the presence of
      H(2), lactate, or pyruvate. Sulfidogenesis occurred with all three electron
      donors and effectively oxidized the c-type cytochrome in lactate- or pyruvate
      reduced, but not H(2)-reduced cells. Correspondingly, electron acceptor
      competition assays with lactate or pyruvate as electron donors showed that
      Fe(III) inhibited U(VI) reduction, and U(VI) inhibited sulfate loss. However,
      sulfate reduction was slowed but not halted when H(2) was the electron donor in
      the presence of Fe(III) or U(VI). U(VI) loss was still impeded by Fe(III) when
      H(2) was used. Hence, we propose a modified pathway for the reduction of sulfate,
      Fe(III), and U(VI) which helps explain why these bacteria cannot grow using these
      metals. We further propose that cytochrome c(3) is an electron carrier involved
      in lactate and pyruvate oxidation and is the reductase for alternate electron
      acceptors with higher redox potentials than sulfate.

PMID- 14711671
TI  - Supplementation of Perkinsus marinus cultures with host plasma or tissue
      homogenate enhances their infectivity.
AB  - The protozoan oyster parasite Perkinsus marinus can be cultured in vitro in a
      variety of media; however, this has been associated with a rapid attenuation of
      infectivity. Supplementation of defined media with products of P. marinus
      susceptible (Crassostrea virginica) and -tolerant (Crassostrea gigas, Crassostrea
      ariakensis) oysters alters proliferation and protease expression profiles and
      induces differentiation into morphological forms typically seen in vivo. It was
      not known if attenuation could be reversed by host extract supplementation. To
      investigate correlations among these changes as well as their association with
      infectivity, the effects of medium supplementation with tissue homogenates from
      both susceptible and tolerant oyster species were examined. The supplements
      markedly altered both cell size and proliferation, regardless of species;
      however, upregulation of low-molecular-weight protease expression was most
      prominent with susceptible oysters extracts. Increased infectivity occurred with
      the use of oyster product-supplemented media, but it was not consistently
      associated with changes in cell size, cell morphology, or protease secretion and
      was not related to the susceptibility of the oyster species used as the
      supplement source.

PMID- 14711672
TI  - Cultivation and growth characteristics of a diverse group of oligotrophic marine
      Gammaproteobacteria.
AB  - Forty-four novel strains of Gammaproteobacteria were cultivated from coastal and
      pelagic regions of the Pacific Ocean using high-throughput culturing methods that
      rely on dilution to extinction in very low nutrient media. Phylogenetic analysis
      showed that the isolates fell into five rRNA clades, all of which contained rRNA
      gene sequences reported previously from seawater environmental gene clone
      libraries (SAR92, OM60, OM182, BD1-7, and KI89A). Bootstrap analyses of
      phylogenetic reliability did not support collapsing these five clades into a
      single clade, and they were therefore named the oligotrophic marine
      Gammaproteobacteria (OMG) group. Twelve cultures chosen to represent the five
      clades were successively purified in liquid culture, and their growth
      characteristics were determined at different temperatures and dissolved organic
      carbon concentrations. The isolates in the OMG group were physiologically diverse
      heterotrophs, and their physiological properties generally followed their
      phylogenetic relationships. None of the isolates in the OMG group formed colonies
      on low- or high-nutrient agar upon their first isolation from seawater, while 7
      of 12 isolates that were propagated for laboratory testing eventually produced
      colonies on 1/10 R2A agar. The isolates grew relatively slowly in natural
      seawater media (1.23 to 2.63 day(-1)), and none of them grew in high-nutrient
      media (>351 mg of C liter(-1)). The isolates were psychro- to mesophilic and
      obligately oligotrophic; many of them were of ultramicrobial size (<0.1 micro
      m(3)). This cultivation study revealed that sporadically detected
      Gammaproteobacteria gene clones from seawater are part of a phylogenetically
      diverse constellation of organisms mainly composed of oligotrophic and
      ultramicrobial lineages that are culturable under specific cultivation
      conditions.

PMID- 14711673
TI  - Differential expression of pine and Cronartium quercuum f. sp. fusiforme genes in
      fusiform rust galls.
AB  - Cronartium quercuum f. sp. fusiforme is the causative agent of fusiform rust
      disease of southern pines in the United States. This disease is characterized by
      the formation of woody branch and stem galls. Differential display was used to
      identify pine genes whose expression is altered by C. quercuum f. sp. fusiforme
      infection and to identify C. quercuum f. sp. fusiforme genes that are expressed
      in fusiform rust galls. Six pine cDNAs that appeared to be differentially
      expressed in galled and healthy stems and 13 C. quercuum f. sp. fusiforme cDNAs
      expressed in galled tissues were identified. A probe that hybridizes specifically
      to C. quercuum f. sp. fusiforme 18S rRNA was used to estimate that 14% of the
      total RNA in fusiform rust galls was from C. quercuum f. sp. fusiforme. This
      finding was used to calibrate gene expression levels in galls when comparing them
      to expression levels in uninfected pines or in isolated C. quercuum f. sp.
      fusiforme cultures. According to Northern analysis and reverse transcriptase PCR
      analysis, all six of the pine clones were expressed at lower levels in galls than
      in healthy tissues. Seven of the nine C. quercuum f. sp. fusiforme clones that
      were assayed were expressed at higher levels in galls than in axenic culture. A
      number of the cDNAs encode proteins that are similar to those that play roles in
      plant development, plant defense, or fungal stress responses.

PMID- 14711674
TI  - Phylogenetic analysis of the hypervariable region of the 18S rRNA gene of
      Cryptosporidium oocysts in feces of Canada geese (Branta canadensis): evidence
      for five novel genotypes.
AB  - To assess genetic diversity in Cryptosporidium oocysts from Canada geese, 161
      fecal samples from Canada geese in the United States were analyzed. Eleven (6.8%)
      were positive for Cryptosporidium spp. following nested PCR amplification of the
      hypervariable region of the 18S rRNA gene. Nine PCR products from geese were
      cloned and sequenced, and all nine diverged from previously reported
      Cryptosporidium 18S rRNA gene sequences. Five sequences were very similar or
      identical to each other but genetically distinct from that of Cryptosporidium
      baileyi; two were most closely related to, but genetically distinct from, the
      first five; and two were distinct from any other sequence analyzed. One
      additional sequence in the hypervariable region of the 18S rRNA gene isolated
      from a cormorant was identical to that of C. baileyi. Phylogenetic analysis
      provided evidence for new genotypes of Cryptosporidium species in Canada geese.
      Results of this study suggest that the taxonomy of Cryptosporidium species in
      geese is complex and that a more complete understanding of genetic diversity
      among these parasites will facilitate our understanding of oocyst sources and
      species in the environment.

PMID- 14711676
TI  - Bacterial diversity in agricultural soils during litter decomposition.
AB  - Denaturing gradient gel electrophoresis (DGGE) of amplified fragments of genes
      coding for 16S rRNA was used to study the development of bacterial communities
      during decomposition of crop residues in agricultural soils. Ten strains were
      tested, and eight of these strains produced a single band. Furthermore, a mixture
      of strains yielded distinguishable bands. Thus, DGGE DNA band patterns were used
      to estimate bacterial diversity. A field experiment performed with litter in
      nylon bags was used to evaluate the bacterial diversity during the decomposition
      of readily degradable rye and more refractory wheat material in comparable
      luvisols and cambisols in northern, central, and southern Germany. The amount of
      bacterial DNA in the fresh litter was small. The DNA content increased rapidly
      after the litter was added to the soil, particularly in the rapidly decomposing
      rye material. Concurrently, diversity indices, such as the Shannon-Weaver index,
      evenness, and equitability, which were calculated from the number and relative
      abundance (intensity) of the bacterial DNA bands amplified from genes coding for
      16S rRNA, increased during the course of decomposition. This general trend was
      not significant for evenness and equitability at any time. The indices were
      higher for the more degradation-resistant wheat straw than for the more easily
      decomposed rye grass. Thus, the DNA band patterns indicated that there was
      increasing bacterial diversity as decomposition proceeded and substrate quality
      decreased. The bacterial diversity differed for the sites in northern, central,
      and southern Germany, where the same litter material was buried in the soil. This
      shows that in addition to litter type climate, vegetation, and indigenous
      microbes in the surrounding soil affected the development of the bacterial
      communities in the litter.

PMID- 14711675
TI  - Characterization of secretory genes ypt1/yptA and nsf1/nsfA from two filamentous
      fungi: induction of secretory pathway genes of Trichoderma reesei under secretion
      stress conditions.
AB  - Two genes involved in protein secretion, encoding the Rab protein YPT1/YPTA and
      the general fusion factor NSFI/NSFA, were characterized from two filamentous
      fungi, Trichoderma reesei and Aspergillus niger var. awamori. The isolated genes
      showed a high level of conservation with their Saccharomyces cerevisiae and
      mammalian counterparts, and T. reesei ypt1 was shown to complement yeast Ypt1p
      depletion. The transcriptional regulation of the T. reesei ypt1, nsf1, and sar1
      genes, involved in protein trafficking, was studied with mycelia treated with the
      folding inhibitor dithiothreitol (DTT) and with brefeldin A, which inhibits
      membrane traffic between the endoplasmic reticulum and Golgi complex. The well
      known inducer of the yeast and T. reesei unfolded protein response (UPR), DTT,
      induced the nsf1 gene and the protein disulfide isomerase gene, pdi1, in both of
      the experiments, and sar1 mRNA increased in only one experiment under strong UPR
      induction. The ypt1 mRNA did not show a clear increase during DTT treatment.
      Brefeldin A strongly induced pdi1 and all of the intracellular trafficking genes
      studied. These results suggest the possibility that the whole secretory pathway
      of T. reesei could be induced at the transcriptional level by stress responses
      caused by protein accumulation in the secretory pathway.

PMID- 14711677
TI  - Species differentiation of a diverse suite of Bacillus spores by mass
      spectrometry-based protein profiling.
AB  - In this study, we demonstrate the versatility of matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOFMS) protein profiling for
      the species differentiation of a diverse suite of Bacillus spores. MALDI-TOFMS
      protein profiles of 11 different strains of Bacillus spores, encompassing nine
      different species, were evaluated. Bacillus species selected for MALDI-TOFMS
      analysis represented the spore-forming bacterial diversity of typical class 100K
      clean room spacecraft assembly facilities. A one-step sample treatment and MALDI
      TOFMS preparation were used to minimize the sample preparation time. A library of
      MALDI-TOFMS spectra was created from these nine Bacillus species, the most
      diverse protein profiling study of the genus reported to date. Linear correlation
      analysis was used to successfully differentiate the MALDI-TOFMS protein profiles
      from all strains evaluated in this study. The MALDI-TOFMS protein profiles were
      compared with 16S rDNA sequences for their bacterial systematics and molecular
      phylogenetic affiliations. The MALDI-TOFMS profiles were found to be
      complementary to the 16S rDNA analysis. Proteomic studies of Bacillus subtilis
      168 were pursued to identify proteins represented by the biomarker peaks in the
      MALDI-TOFMS spectrum. Four small, acid-soluble proteins (A, B, C, and D), one DNA
      binding protein, hypothetical protein ymf J, and four proteins associated with
      the spore coat and spore coat formation (coat JB, coat F, coat T, and spoIVA)
      were identified. The ability to visualize higher-molecular-mass coat proteins (10
      to 25 kDa) as well as smaller proteins (<10 kDa) with MALDI-TOFMS profiling is
      critical for the complete and effective species differentiation of the Bacillus
      genus.

PMID- 14711678
TI  - Molecular and metabolic characterization of cold-tolerant alpine soil Pseudomonas
      sensu stricto.
AB  - Alpine soils undergo dramatic temporal changes in their microclimatic properties,
      suggesting that the bacteria there encounter uncommon shifting selection
      gradients. Pseudomonads constitute important members of the alpine soil
      community. In order to characterize the alpine Pseudomonas community and to
      assess the impact of shifting selection on this community, we examined the
      ability of cold-tolerant Pseudomonas isolates to grow on a variety of carbon
      sources, and we determined their phylogenetic relationships based on 16S
      ribosomal DNA sequencing. We found a high prevalence of Pseudomonas in our soil
      samples, and isolates from these soils exhibited extensive metabolic diversity.
      In addition, our data revealed that many of our isolates form a unique cold
      adapted clade, representatives of which are also found in the Swedish tundra and
      Antarctica. Our data also show a lack of concordance between the metabolic
      properties and 16S phylogeny, indicating that the metabolic diversity of these
      organisms cannot be predicted by phylogeny.

PMID- 14711679
TI  - Nutrient shock and incubation atmosphere influence recovery of culturable
      Helicobacter pylori from water.
AB  - Three different media-Columbia agar, Wilkins-Chalgren agar, and Helicobacter
      pylori special peptone agar-were prepared in a diluted version and compared to
      the standard medium formulation in order to study a possible nutrient shock
      effect observed when recovering H. pylori from water by counting the number of
      CFU. This same parameter was subsequently used to evaluate the influence of the
      incubation atmosphere by using a modular atmosphere-controlled system to provide
      different atmospheres and by employing an established gas generation kit as a
      control. Both a low nutrient content of the media and a rapidly achieved
      microaerophilic incubation atmosphere proved to increase the numbers of
      environment-stressed H. pylori organisms recovered. An atmosphere of 5% CO(2), 5%
      O(2), and 3% H(2) is recommended, although other atmospheres with a low oxygen
      concentration are also acceptable. Besides highlighting and assessing the
      importance of several factors in the culturability of H. pylori, this paper
      demonstrates the potential ability to develop an optimized technique for recovery
      of this pathogen from water.

PMID- 14711680
TI  - Improved method for polynucleotide probe-based cell sorting, using DNA-coated
      microplates.
AB  - We developed an improved method for cultivation-independent sorting of bacterial
      cells. The technique is based on labeling the target cells by in situ
      hybridization with polynucleotide transcript probes. Due to the probes' length,
      part of the probe remains outside the cell and can subsequently be used to
      capture the cells. Target cells are immobilized during a second hybridization
      step in microplates that are coated with DNA that is complementary to the probe
      sequence. The method was applied successfully to artificial mixtures of cells
      with polynucleotide probes targeting either rRNA, a plasmid-borne beta-lactamase
      gene, or a chromosome-borne glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      gene. Cells could be separated based on phylogenetic parameters (using rRNA
      targeted probes) as well as on other DNA-encoded traits.

PMID- 14711681
TI  - Rapid detection of Vibrio vulnificus in shellfish and Gulf of Mexico water by
      real-time PCR.
AB  - In this paper we describe optimization of SYBR Green I-based real-time PCR
      parameters and testing of a large number of microbial species with vvh-specific
      oligonucleotide primers to establish a rapid, specific, and sensitive method for
      detection of Vibrio vulnificus in oyster tissue homogenate and Gulf of Mexico
      water (gulf water). Selected oligonucleotide primers for the vvh gene were tested
      for PCR amplification of a 205-bp DNA fragment with a melting temperature of
      approximately 87 degrees C for 84 clinical and environmental strains of V.
      vulnificus. No amplification was observed with other vibrios or nonvibrio strains
      with these primers. The minimum level of detection by the real-time PCR method
      was 1 pg of purified genomic DNA or 10(2) V. vulnificus cells in 1 g of
      unenriched oyster tissue homogenate or 10 ml of gulf water. It was possible to
      improve the level of detection to one V. vulnificus cell in samples that were
      enriched for 5 h. The standard curves prepared from the real-time PCR cycle
      threshold values revealed that there was a strong correlation between the number
      of cells in unenriched samples and the number of cells in enriched samples.
      Detection of a single cell of V. vulnificus in 1 g of enriched oyster tissue
      homogenate is in compliance with the recent Interstate Shellfish Sanitation
      Conference guidelines. The entire detection method, including sample processing,
      enrichment, and real-time PCR amplification, was completed within 8 h, making it
      a rapid single-day assay. Rapid and sensitive detection of V. vulnificus would
      ensure a steady supply of postharvest treated oysters to consumers, which should
      help decrease the number of illnesses or outbreaks caused by this pathogen.

PMID- 14711682
TI  - Biodegradation of nitro-substituted explosives 2,4,6-trinitrotoluene, hexahydro
      1,3,5-trinitro-1,3,5-triazine, and octahydro-1,3,5,7-tetranitro-1,3,5-tetrazocine
      by a phytosymbiotic Methylobacterium sp. associated with poplar tissues (Populus
      deltoides x nigra DN34).
AB  - A pink-pigmented symbiotic bacterium was isolated from hybrid poplar tissues
      (Populus deltoides x nigra DN34). The bacterium was identified by 16S and 16S-23S
      intergenic spacer ribosomal DNA analysis as a Methylobacterium sp. (strain
      BJ001). The isolated bacterium was able to use methanol as the sole source of
      carbon and energy, which is a specific attribute of the genus Methylobacterium.
      The bacterium in pure culture was shown to degrade the toxic explosives 2,4,6
      trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazene (RDX), and
      octahydro-1,3,5,7-tetranitro-1,3,5-tetrazocine (HMX). [U-ring-(14)C]TNT (25 mg
      liter(-1)) was fully transformed in less than 10 days. Metabolites included the
      reduction derivatives amino-dinitrotoluenes and diamino-nitrotoluenes. No
      significant release of (14)CO(2) was recorded from [(14)C]TNT. In addition, the
      isolated methylotroph was shown to transform [U-(14)C]RDX (20 mg liter(-1)) and
      [U-(14)C]HMX (2.5 mg liter(-1)) in less than 40 days. After 55 days of
      incubation, 58.0% of initial [(14)C]RDX and 61.4% of initial [(14)C]HMX were
      mineralized into (14)CO(2). The radioactivity remaining in solution accounted for
      12.8 and 12.7% of initial [(14)C]RDX and [(14)C]HMX, respectively. Metabolites
      detected from RDX transformation included a mononitroso RDX derivative and a
      polar compound tentatively identified as methylenedinitramine. Since members of
      the genus Methylobacterium are distributed in a wide diversity of natural
      environments and are very often associated with plants, Methylobacterium sp.
      strain BJ001 may be involved in natural attenuation or in situ biodegradation
      (including phytoremediation) of explosive-contaminated sites.

PMID- 14711683
TI  - In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei
      strain Shirota.
AB  - We studied the potential inhibitory effect of Lactobacillus casei strain Shirota
      (from the fermented milk product Yakult [Yakult Ltd., Tokyo, Japan]) on
      Helicobacter pylori by using (i) in vitro inhibition assays with H. pylori SS1
      (Sydney strain 1) and nine H. pylori clinical isolates and (ii) the in vivo H.
      pylori SS1 mouse model of infection over a period of 9 months. In vitro activity
      against H. pylori SS1 and all of the clinical isolates was observed in the
      presence of viable L. casei strain Shirota cells but not in the cell-free culture
      supernatant, although there was profound inhibition of urease activity. In vivo
      experiments were performed by oral administration of L. casei strain Shirota in
      the water supply over a period of 9 months to 6-week-old C57BL/6 mice previously
      infected with H. pylori SS1 (study group; n = 25). Appropriate control groups of
      H. pylori-infected but untreated animals (n = 25) and uninfected animals given L.
      casei strain Shirota (n = 25) also were included in the study. H. pylori
      colonization and development of gastritis were assessed at 1, 2, 3, 6, and 9
      months postinfection. A significant reduction in the levels of H. pylori
      colonization was observed in the antrum and body mucosa in vivo in the
      lactobacillus-treated study group, as assessed by viable cultures, compared to
      the levels in the H. pylori-infected control group. This reduction was
      accompanied by a significant decline in the associated chronic and active gastric
      mucosal inflammation observed at each time point throughout the observation
      period. A trend toward a decrease in the anti-H. pylori immunoglobulin G response
      was measured in the serum of the animals treated with lactobacillus, although
      this decrease was not significant.

PMID- 14711684
TI  - Rapid detection of Escherichia coli O157:H7 by using green fluorescent protein
      labeled PP01 bacteriophage.
AB  - A previously isolated T-even-type PP01 bacteriophage was used to detect its host
      cell, Escherichia coli O157:H7. The phage small outer capsid (SOC) protein was
      used as a platform to present a marker protein, green fluorescent protein (GFP),
      on the phage capsid. The DNA fragment around soc was amplified by PCR and
      sequenced. The gene alignment of soc and its upstream region was g56-soc.2-soc.1
      soc, which is the same as that for T2 phage. GFP was introduced into the C- and N
      terminal regions of SOC to produce recombinant phages PP01-GFP/SOC and PP01
      SOC/GFP, respectively. Fusion of GFP to SOC did not change the host range of
      PP01. On the contrary, the binding affinity of the recombinant phages to the host
      cell increased. However, the stability of the recombinant phages in alkaline
      solution decreased. Adsorption of the GFP-labeled PP01 phages to the E. coli cell
      surface enabled visualization of cells under a fluorescence microscope. GFP
      labeled PP01 phage was not only adsorbed on culturable E. coli cells but also on
      viable but nonculturable or pasteurized cells. The coexistence of insensitive E.
      coli K-12 (W3110) cells did not influence the specificity and affinity of GFP
      labeled PP01 adsorption on E. coli O157:H7. After a 10-min incubation with GFP
      labeled PP01 phage at a multiplicity of infection of 1,000 at 4 degrees C, E.
      coli O157:H7 cells could be visualized by fluorescence microscopy. The GFP
      labeled PP01 phage could be a rapid and sensitive tool for E. coli O157:H7
      detection.

PMID- 14711685
TI  - Bradyrhizobium elkanii rtxC gene is required for expression of symbiotic
      phenotypes in the final step of rhizobitoxine biosynthesis.
AB  - We disrupted the rtxC gene on the chromosome of Bradyrhizobium elkanii USDA94 by
      insertion of a nonpolar aph cartridge. The rtxC mutant, designated DeltartxC,
      produced serinol and dihydrorhizobitoxine but no rhizobitoxine, both in culture
      and in planta. The introduction of cosmids harboring the rtxC gene into the
      DeltartxC mutant complemented rhizobitoxine production, suggesting that rtxC is
      involved in the final step of rhizobitoxine biosynthesis in B. elkanii USDA94.
      Glycine max cv. Lee inoculated with DeltartxC or with a null mutant,
      Deltartx::Omega1, showed no foliar chlorosis, whereas the wild-type strain USDA94
      caused severe foliar chlorosis. The two mutants showed significantly less
      nodulation competitiveness than the wild-type strain on Macroptilium
      atropurpureum. These results indicate that dihydrorhizobitoxine, the immediate
      precursor of the oxidative form of rhizobitoxine, has no distinct effect on
      nodulation phenotype in these legumes. Thus, desaturation of dihydrorhizobitoxine
      by rtxC-encoded protein is essential for the bacterium to show rhizobitoxine
      phenotypes in planta. In addition, complementation analysis of rtxC by cosmids
      differing in rtxC transcription levels suggested that rhizobitoxine production
      correlates with the amount of rtxC transcript.

PMID- 14711686
TI  - Role of two G-protein alpha subunits, TgaA and TgaB, in the antagonism of plant
      pathogens by Trichoderma virens.
AB  - G-protein alpha subunits are involved in transmission of signals for development,
      pathogenicity, and secondary metabolism in plant pathogenic and saprophytic
      fungi. We cloned two G-protein alpha subunit genes, tgaA and tgaB, from the
      biocontrol fungus Trichoderma virens. tgaA belongs to the fungal Galphai class,
      while tgaB belongs to the class defined by gna-2 of Neurospora crassa. We
      compared loss-of-function mutants of tgaA and tgaB with the wild type for radial
      growth, conidiation, germination of conidia, the ability to overgrow colonies of
      Rhizoctonia solani and Sclerotium rolfsii in confrontation assays, and the
      ability to colonize the sclerotia of these pathogens in soil. Both mutants grew
      as well as the wild type, sporulated normally, did not sporulate in the dark, and
      responded to blue light by forming a conidial ring. The tgaA mutants germinated
      by straight unbranched germ tubes, while tgaB mutants, like the wild type,
      germinated by wavy and highly branched germ tubes. In confrontation assays, both
      tgaA and tgaB mutants and the wild type overgrew, coiled, and lysed the mycelia
      of R. solani, but tgaA mutants had reduced ability to colonize S. rolfsii
      colonies. In the soil plate assay, both mutants parasitized the sclerotia of R.
      solani, but tgaA mutants were unable to parasitize the sclerotia of S. rolfsii.
      Thus, tgaA is involved in antagonism against S. rolfsii, but neither G protein
      subunit is involved in antagonism against R. solani. T. virens, which has a wide
      host range, thus employs a G-protein pathway in a host-specific manner.

PMID- 14711687
TI  - Bacterial Activity at -2 to -20 degrees C in Arctic wintertime sea ice.
AB  - Arctic wintertime sea-ice cores, characterized by a temperature gradient of -2 to
      -20 degrees C, were investigated to better understand constraints on bacterial
      abundance, activity, and diversity at subzero temperatures. With the fluorescent
      stains 4',6'-diamidino-2-phenylindole 2HCl (DAPI) (for DNA) and 5-cyano-2,3
      ditoyl tetrazolium chloride (CTC) (for O(2)-based respiration), the abundances of
      total, particle-associated (>3- micro m), free-living, and actively respiring
      bacteria were determined for ice-core samples melted at their in situ
      temperatures (-2 to -20 degrees C) and at the corresponding salinities of their
      brine inclusions (38 to 209 ppt). Fluorescence in situ hybridization was applied
      to determine the proportions of Bacteria, Cytophaga-Flavobacteria-Bacteroides
      (CFB), and Archaea. Microtome-prepared ice sections also were examined
      microscopically under in situ conditions to evaluate bacterial abundance (by DAPI
      staining) and particle associations within the brine-inclusion network of the
      ice. For both melted and intact ice sections, more than 50% of cells were found
      to be associated with particles or surfaces (sediment grains, detritus, and ice
      crystal boundaries). CTC-active bacteria (0.5 to 4% of the total) and cells
      detectable by rRNA probes (18 to 86% of the total) were found in all ice samples,
      including the coldest (-20 degrees C), where virtually all active cells were
      particle associated. The percentage of active bacteria associated with particles
      increased with decreasing temperature, as did the percentages of CFB (16 to 82%
      of Bacteria) and Archaea (0.0 to 3.4% of total cells). These results, combined
      with correlation analyses between bacterial variables and measures of particulate
      matter in the ice as well as the increase in CFB at lower temperatures, confirm
      the importance of particle or surface association to bacterial activity at
      subzero temperatures. Measuring activity down to -20 degrees C adds to the
      concept that liquid inclusions in frozen environments provide an adequate habitat
      for active microbial populations on Earth and possibly elsewhere.

PMID- 14711688
TI  - Genotypic and phenotypic studies of murine intestinal lactobacilli: species
      differences in mice with and without colitis.
AB  - Lactobacilli represent components of the commensal mammalian gastrointestinal
      microbiota and are useful as probiotics, functional foods, and dairy products.
      This study includes systematic polyphasic analyses of murine intestinal
      Lactobacillus isolates and correlation of taxonomic findings with data from
      cytokine production assays. Lactobacilli were recovered from mice with microbiota
      dependent colitis (interleukin-10 [IL-10]-deficient C57BL/6 mice) and from mice
      without colitis (Swiss Webster and inducible nitric oxide synthetase-deficient
      C57BL/6 mice). Polyphasic analyses were performed to elucidate taxonomic
      relationships among 88 reference and murine gastrointestinal lactobacilli.
      Genotypic tests included single-locus analyses (16S ribosomal DNA sequencing and
      16S-23S rRNA intergenic spacer region PCR) and genomic DNA profiling (repetitive
      DNA element-based PCR), and phenotypic analyses encompassed more than 50 tests
      for carbohydrate utilization, enzyme production, and antimicrobial resistance.
      From 20 mice without colitis, six Lactobacillus species were recovered; the
      majority of the mice were colonized with L. reuteri or L. murinus (72% of
      isolates). In contrast, only, L. johnsonii was isolated from 14 IL-10-deficient
      mice. Using an in vitro assay, we screened murine isolates for their ability to
      inhibit tumor necrosis factor alpha (TNF-alpha) secretion by lipopolysaccharide
      activated macrophages. Interestingly, a subpopulation of lactobacilli recovered
      from mice without colitis displayed TNF-alpha inhibitory properties, whereas none
      of the L. johnsonii isolates from IL-10-deficient mice exhibited this effect. We
      propose that differences among intestinal Lactobacillus populations in mammals,
      combined with host genetic susceptibilities, may account partly for variations in
      host mucosal responses.

PMID- 14711689
TI  - Microstructural characterization of cyanobacterial mats from the McMurdo Ice
      Shelf, Antarctica.
AB  - The three-dimensional structures of two types of cyanobacterium-dominated
      microbial mats from meltwater ponds on the McMurdo Ice Shelf were as determined
      by using a broad suite of complementary techniques, including optical and
      fluorescence microscopy, confocal scanning laser microscopy, scanning electron
      microscopy with back-scattered electron-imaging mode, low-temperature scanning
      electron microscopy, and microanalyitical X-ray energy dispersive spectroscopy.
      By using a combination of the different in situ microscopic techniques, the
      Antarctic microbial mats were found to be structures with vertical stratification
      of groups of cyanobacteria and mineral sediments, high contents of extracellular
      polymeric substances, and large void spaces occupied by water. In cyanobacterium
      rich layers, heterocystous nostocalean and nonheterocystous oscillatorialean taxa
      were the most abundant taxa and appeared to be intermixed with fine-size deposits
      of epicellular silica and calcium carbonate. Most of the cyanobacterial filaments
      had similar orientations in zones without sediment particles, but thin filaments
      were tangled among thicker filaments. The combination of the microscopic
      techniques used showed the relative positions of biological and mineral entities
      within the microbial mats and enabled some speculation about their interactions.

PMID- 14711690
TI  - Development of genetic techniques for the psychrotrophic fish pathogen
      Flavobacterium psychrophilum.
AB  - Flavobacterium psychrophilum, a member of the Cytophaga-Flavobacterium
      Bacteroides group, is an important pathogen of salmonid fish. Previous attempts
      to develop genetic techniques for this fastidious, psychrotrophic bacterium have
      met with failure. Here we describe the development of techniques for the genetic
      manipulation of F. psychrophilum and the identification of plasmids, selectable
      markers, a reporter system, and a transposon that function in several isolates of
      this fish pathogen. The antibiotic resistance genes ermF, cfxA, and tetQ function
      in F. psychrophilum. Cloning vectors based on the F. psychrophilum cryptic
      plasmid pCP1 which carried these selectable markers were introduced by
      conjugation from E. coli, resulting in antibiotic-resistant colonies of F.
      psychrophilum. Conjugative transfer of DNA into F. psychrophilum was strain
      dependent. Efficient transfer was observed for two of the seven strains tested
      (THC02-90 and THC04-90). E. coli lacZY functioned in F. psychrophilum when
      expressed from a pCP1 promoter, allowing its development as a reporter for
      studies of gene expression. Plasmids isolated from F. psychrophilum were
      efficiently introduced into F. psychrophilum by electroporation, but plasmids
      isolated from E. coli were not suitable for transfer by this route, suggesting
      the presence of a restriction barrier. DNA isolated from F. psychrophilum was
      resistant to digestion by Sau3AI and BamHI, indicating that a Sau3AI-like
      restriction modification system may constitute part of this barrier. Tn4351 was
      introduced into F. psychrophilum from E. coli and transposed with apparent
      randomness, resulting in erythromycin-resistant colonies. The techniques
      developed in this study allow for genetic manipulation and analysis of this
      important fish pathogen.

PMID- 14711691
TI  - Use of stable-isotope probing, full-cycle rRNA analysis, and fluorescence in situ
      hybridization-microautoradiography to study a methanol-fed denitrifying microbial
      community.
AB  - A denitrifying microbial consortium was enriched in an anoxically operated,
      methanol-fed sequencing batch reactor (SBR) fed with a mineral salts medium
      containing methanol as the sole carbon source and nitrate as the electron
      acceptor. The SBR was inoculated with sludge from a biological nutrient removal
      activated sludge plant exhibiting good denitrification. The SBR denitrification
      rate improved from less than 0.02 mg of NO(3)(-)-N mg of mixed-liquor volatile
      suspended solids (MLVSS)(-1) h(-1) to a steady-state value of 0.06 mg of NO(3)(-)
      N mg of MLVSS(-1) h(-1) over a 7-month operational period. At this time, the
      enriched microbial community was subjected to stable-isotope probing (SIP) with
      [(13)C]methanol to biomark the DNA of the denitrifiers. The extracted [(13)C]DNA
      and [(12)C]DNA from the SIP experiment were separately subjected to full-cycle
      rRNA analysis. The dominant 16S rRNA gene phylotype (group A clones) in the
      [(13)C]DNA clone library was closely related to those of the obligate
      methylotrophs Methylobacillus and Methylophilus in the order Methylophilales of
      the Betaproteobacteria (96 to 97% sequence identities), while the most abundant
      clone groups in the [(12)C]DNA clone library mostly belonged to the family
      Saprospiraceae in the Bacteroidetes phylum. Oligonucleotide probes for use in
      fluorescence in situ hybridization (FISH) were designed to specifically target
      the group A clones and Methylophilales (probes DEN67 and MET1216, respectively)
      and the Saprospiraceae clones (probe SAP553). Application of these probes to the
      SBR biomass over the enrichment period demonstrated a strong correlation between
      the level of SBR denitrification and relative abundance of DEN67-targeted
      bacteria in the SBR community. By contrast, there was no correlation between the
      denitrification rate and the relative abundances of the well-known denitrifying
      genera Hyphomicrobium and Paracoccus or the Saprospiraceae clones visualized by
      FISH in the SBR biomass. FISH combined with microautoradiography independently
      confirmed that the DEN67-targeted cells were the dominant bacterial group capable
      of anoxic [(14)C]methanol uptake in the enriched biomass. The well-known
      denitrification lag period in the methanol-fed SBR was shown to coincide with a
      lag phase in growth of the DEN67-targeted denitrifying population. We conclude
      that Methylophilales bacteria are the dominant denitrifiers in our SBR system and
      likely are important denitrifiers in full-scale methanol-fed denitrifying
      sludges.

PMID- 14711692
TI  - Quantum dots as a novel immunofluorescent detection system for Cryptosporidium
      parvum and Giardia lamblia.
AB  - Semiconductor quantum dot-conjugated antibodies were successfully developed to
      label Cryptosporidium parvum and Giardia lamblia. This novel fluorescence system
      exhibited superior photostability, gave 1.5- to 9-fold-higher signal-to-noise
      ratios than traditional organic dyes in detecting C. parvum, and allowed dual
      color detection for C. parvum and G. lamblia.

PMID- 14711693
TI  - Analysis of the gyrA gene of clinical Yersinia ruckeri isolates with reduced
      susceptibility to quinolones.
AB  - Antimicrobial susceptibility of seven clinical strains of Yersinia ruckeri
      representative of those isolated between 1994 and 2002 from a fish farm with
      endemic enteric redmouth disease was studied. All isolates displayed
      indistinguishable pulsed-field gel electrophoresis restriction patterns,
      indicating that they represented a single strain. However, considering both
      inhibition zone diameters (IZD) and MICs, the isolates recovered in 2001-2002
      formed a separate cluster with lower levels of susceptibility to all the
      quinolones tested, especially nalidixic acid (NA) and oxolinic acid (OA),
      compared with the isolates recovered between 1994 and 1998. Analysis of the PCR
      product of the quinolone resistance-determining region of the gyrA gene from
      clinical isolates of Y. ruckeri with reduced susceptibility to OA and NA revealed
      a single amino acid substitution, Ser-83 to Arg-83 (Escherichia coli numbering).
      Identical substitution was observed in induced OA-resistant mutant strains, which
      displayed IZD and MICs of quinolones similar to those of the clinical isolates of
      Y. ruckeri with reduced susceptibility to these antimicrobial agents. These data
      indicate in that for Y. ruckeri, the substitution of Ser by Arg at position 83 of
      the gyrA gene is associated with reduced susceptibility to quinolones.

PMID- 14711694
TI  - Cloning and heterologous expression of hematin-dependent catalase produced by
      Lactobacillus plantarum CNRZ 1228.
AB  - Lactobacillus plantarum CNRZ 1228 exhibited heme-dependent catalase activity
      under environmental conditions similar to those encountered during sausage
      fermentation. The 1,455-bp catalase gene (katL) was cloned and encoded a protein
      of 484 amino acids. Expression of katL in a heterologous host showed that katL
      encodes a functional catalase. PCR screening of selected strains of lactic acid
      bacteria for katL indicated the presence of similar genes in other strains of
      lactobacilli.

PMID- 14711695
TI  - A complete library of amino acid alterations at N304 in Streptomyces clavuligerus
      deacetoxycephalosporin C synthase elucidates the basis for enhanced penicillin
      analogue conversion.
AB  - N304 of Streptomyces clavuligerus deacetoxycephalosporin C synthase was
      mutagenized to alter its catalytic ability. Given that N304A, N304K, N304L, and
      N304R mutant enzymes exhibited significant improvements in penicillin analogue
      conversions, we advocate that replacement of N304 with residues with aliphatic or
      basic side chains is preferable for engineering of a hypercatalytic enzyme.

PMID- 14711696
TI  - Simple and reliable method to precipitate proteins from bacterial culture
      supernatant.
AB  - A simple and reliable method for precipitating protein from bacterial culture
      supernatants based on a pyrogallol red-molybdate-methanol (PRMM) protocol has
      been developed and applied for the analysis of proteins secreted by a bacterial
      type III secretion system. PRMM-based precipitation has been shown to be more
      efficient and robust than are conventional protocols.

PMID- 14711697
TI  - Pet snakes as a reservoir for Salmonella enterica subsp. diarizonae (Serogroup
      IIIb): a prospective study.
AB  - Reptile-associated Salmonella infections are an increasing problem for humans. We
      have prospectively screened two breeding groups of 16 pet snakes for colonization
      with Salmonella species. Various serovars of S. enterica subsp. diarizonae were
      found in 81% of the snakes. To avoid transmission, strict hygienic precautions
      should be applied when reptiles are handled.

PMID- 14711699
TI  - Sensitive and rapid detection of edwardsiellosis in fish by a loop-mediated
      isothermal amplification method.
AB  - Here we report a rapid and sensitive method (using loop-mediated isothermal
      amplification [LAMP]) for the diagnosis of edwardsiellosis, a fish disease caused
      by Edwardsiella tarda, in Japanese flounder. A set of four primers was designed,
      and conditions for the detection were optimized for the detection of E. tarda in
      45 min at 65 degrees C. No amplification of the target hemolysin gene was
      detected in other related bacteria. When the LAMP primers were used, detection of
      edwardsiellosis in infected Japanese flounder kidney, and spleen and seawater
      cultures was possible. We have developed a rapid and sensitive diagnostic
      protocol for edwardsiellosis detection in fish. This is the first report of the
      application of LAMP for the diagnosis of a fish pathogen.

PMID- 14711698
TI  - Intracellular symbionts and other bacteria associated with deer ticks (Ixodes
      scapularis) from Nantucket and Wellfleet, Cape Cod, Massachusetts.
AB  - The diversity of bacteria associated with the deer tick (Ixodes scapularis) was
      assessed using PCR amplification, cloning, and sequencing of 16S rRNA genes
      originating from seven ticks collected from Nantucket Island and Wellfleet, Cape
      Cod, Mass. The majority of sequences obtained originated from gram-negative
      proteobacteria. Four intracellular bacteria were detected including strains of
      Ehrlichia, Rickettsia, and Wolbachia and an organism related to intracellular
      insect symbionts from the Cytophaga-Flavobacterium-Bacteroides group. Several
      strains of members of the Sphingomonadaceae were also detected in all but one
      tick. The results provide a view of the diversity of bacteria associated with I.
      scapularis ticks in the field.

PMID- 14711700
TI  - Molecular cloning, purification, and biochemical characterization of hydantoin
      racemase from the legume symbiont Sinorhizobium meliloti CECT 4114.
AB  - Hydantoin racemase from Sinorhizobium meliloti was functionally expressed in
      Escherichia coli. The native form of the enzyme was a homotetramer with a
      molecular mass of 100 kDa. The optimum temperature and pH for the enzyme were 40
      degrees C and 8.5, respectively. The enzyme showed a slight preference for
      hydantoins with short rather than long aliphatic side chains or those with
      aromatic rings. Substrates, which showed no detectable activity toward the
      enzyme, were found to exhibit competitive inhibition.

PMID- 14711701
TI  - Identification of bacilysin, chlorotetaine, and iturin a produced by Bacillus sp.
      strain CS93 isolated from pozol, a Mexican fermented maize dough.
AB  - Three antimicrobial compounds produced by Bacillus sp. strain CS93 isolated from
      pozol were identified by using high-performance liquid chromatography and mass
      spectrometry. The three compounds were iturin, bacilysin, and chlorotetaine.
      Production of these compounds by CS93 could account for the medicinal properties
      attributed to pozol.

PMID- 14711702
TI  - Combined effects of high hydrostatic pressure and temperature for inactivation of
      Bacillus anthracis spores.
AB  - Spores of Bacillus anthracis are known to be extremely resistant to heat
      treatment, irradiation, desiccation, and disinfectants. To determine inactivation
      kinetics of spores by high pressure, B. anthracis spores of a Sterne strain
      derived mutant deficient in the production of the toxin components (strain RP42)
      were exposed to pressures ranging from 280 to 500 MPa for 10 min to 6 h, combined
      with temperatures ranging from 20 to 75 degrees C. The combination of heat and
      pressure resulted in complete destruction of B. anthracis spores, with a D value
      (exposure time for 90% inactivation of the spore population) of approximately 4
      min after pressurization at 500 MPa and 75 degrees C, compared to 160 min at 500
      MPa and 20 degrees C and 348 min at atmospheric pressure (0.1 MPa) and 75 degrees
      C. The use of high pressure for spore inactivation represents a considerable
      improvement over other available methods of spore inactivation and could be of
      interest for antigenic spore preparation.

PMID- 14711703
TI  - Role of aminotransferase IlvE in production of branched-chain fatty acids by
      Lactococcus lactis subsp. lactis.
AB  - The objective of this study was to determine the role of a lactococcal branched
      chain amino acid aminotransferase gene, ilvE, in the production of branched-chain
      fatty acids. Lactococcus lactis subsp. lactis LM0230 and an ilvE deletion mutant,
      JLS450, produced branched-chain fatty acids from amino and alpha-keto acids at
      levels above alpha-keto acid spontaneous degradation and the fatty acids' flavor
      thresholds. The deletion mutant produced the same amounts of branched-chain fatty
      acids from precursor amino acids as did the parent. This was not the case,
      however, for the production of branched-chain fatty acids from the corresponding
      precursor alpha-keto acids. The deletion mutant produced a set of fatty acids
      different from that produced by the parent. We concluded from these observations
      that ilvE plays a role in the specific type of fatty acids produced but has
      little influence on the total amount of fatty acids produced by lactococci.

PMID- 14711704
TI  - Neonatal-mouse infectivity of intact Cryptosporidium parvum oocysts isolated
      after optimized in vitro excystation.
AB  - We reexamined the finding of Neumann et al. that intact Cryptosporidium parvum
      oocysts obtained after in vitro excystation were infectious for neonatal CD-1
      mice. We used both established excystation protocols and our own protocol that
      maximized excystation. Although intact oocysts isolated after any of three
      protocols were infectious for neonatal CD-1 mice, the infectivity of intact
      oocysts isolated with our optimized excystation protocol was significantly lower
      than the infectivity of intact oocysts isolated after established protocols or
      from fresh oocysts. Excystation should not be considered a valid measure of C.
      parvum viability, given that it is biologically implausible for oocysts to be
      nonviable and yet infectious.

PMID- 14711705
TI  - Night vision after LASIK: the pupil proclaims innocence.

PMID- 14711706
TI  - Risk factors for night vision complaints after LASIK for myopia.
AB  - PURPOSE: To study the preoperative risk factors for night vision complaints
      (NVCs) after LASIK in a clinical setting. DESIGN: Retrospective noncomparative
      case series. PARTICIPANTS: Seven hundred ninety-five patients (1488 eyes) who
      underwent LASIK for myopia up to -9.75 diopters (D) (from January 1 to December
      31, 1999). SETTING: Private clinic. METHODS: A complete preoperative examination
      was performed. Patients had bilateral LASIK surgery using the Nidek EC-5000 non
      wavefront guided slit-scanning excimer laser and the Moria LSK One microkeratome.
      Patients were observed postoperatively for 12 months. MAIN OUTCOME MEASURES: The
      reported NVCs for each eye were rated on a subjective scale based on functional
      visual comfort. Clinically important NVC odds ratios (ORs) were calculated.
      RESULTS: Reports of NVCs decreased considerably from 25.6% at 1 month to 4.7% at
      12 months postoperatively, at which time all patients reported similar NVCs in
      both eyes. Stratification of risk factors at 12 months postoperatively showed a
      2.8-times increase in NVCs for initial myopia of >5 D, a 2.5-times increase for
      an optical zone of </=6.0 mm, and a 2.9-times increase for a postoperative
      spherical equivalent outside +/-0.5 D of emmetropia. The role of attempted
      spherical correction, age of the patient, and postoperative spherical equivalent
      had significant importance in logistic regression of the OR throughout the first
      postoperative year. In a stepwise logistic regression using 6- and 12-month data,
      attempted spherical correction and optical zone were the most predictive factors
      of NVCs (P<0.001). Pupil size at any month postoperatively was not statistically
      predictive of postoperative NVCs in any differential model involving it.
      CONCLUSIONS: Attempted degree of spherical correction, age, optical zone, and
      postoperative spherical equivalent were major risk factors of NVCs throughout the
      first postoperative year, whereas pupil size was not. Future wavefront studies
      that characterize higher order aberrations might be helpful for understanding
      individual visual aberrations while predicting quality of vision.

PMID- 14711707
TI  - Corneal epithelial adhesion abnormalities associated with LASIK.
AB  - PURPOSE: To assess the clinical characteristics, incidence, and pathologic
      correlation of corneal epithelial adhesion abnormalities encountered during
      LASIK. DESIGN: Prospective noncomparative interventional case series.
      PARTICIPANTS: Five hundred consecutive eyes of 268 patients undergoing primary
      LASIK procedures by one surgeon utilizing the Moria LSK One microkeratome and
      VISX Star S-2 excimer laser. METHODS: Corneal epithelial adhesion was assessed
      immediately preoperatively using a cellulose surgical sponge (adhesion test), and
      the incidence, extent, and location of epithelial defects occurring during the
      microkeratome incision of the corneal flap were recorded. Epithelial specimens
      from 7 corneas requiring debridement of dysadhesive epithelium were examined by
      transmission electron microscopy. MAIN OUTCOME MEASURES: The characteristics of
      the study population (age, gender, contact lens use, relevant ocular surface or
      systemic disease, refractive error, keratometry, pachymetry) and the
      microkeratome-related variables (head selection and vacuum level) were compared
      with the results of the preoperative epithelial adhesion test, the development of
      intraoperative epithelial effects (size and location), and the postoperative
      outcome. RESULTS: Epithelial defects were sustained by 51 corneas (10.2%), and
      among these, 31 (6.2%) were microdefects and 20 (4.0%) were macrodefects. The
      adhesion test was positive (indicative of compromised adhesion of epithelium to
      stroma) in 20 (64.5%) corneas with microdefects, but false negatives (epithelial
      defect despite negative adhesion test) occurred in 11 cases (35.4%). The adhesion
      test was positive in 16 (80%) of corneas having macrodefects, with 4 (20%) false
      negatives. Thus, the overall positive predictive value of the adhesion test was
      59%, and the percentage of positive prediction was 92% (Bayes' theorem). Among
      all other outcome measures assessed, only corneal flap thickness seemed a
      potential risk factor, as 40 (78.4%) epithelial defects were associated with the
      creation of a 180- micro m-thick flap, whereas 10 (19.6%) were associated with a
      160- micro m-thick flap and only 1 (2%) occurred with a 130- micro m flap. These
      trends were not, however, statistically significant (P = 0.15, Fisher exact
      test). Transmission electron microscopy of all epithelial debridement specimens
      disclosed consistent abnormality of the basement membrane adhesion complex, as
      thickened and multilaminated basement membrane remained adherent to the intact
      epithelial sheet. CONCLUSIONS: : Corneal epithelial dysadhesion and defects
      occurring in the course of LASIK surgery may be associated with an intrinsic
      compromise of the basement membrane adhesion complex, as evidenced clinically by
      the adhesion test and demonstrated pathologically by duplicated basement
      membrane.

PMID- 14711708
TI  - Plastic particles at the LASIK interface.
AB  - PURPOSE: To investigate the origin, composition, and persistence of the interface
      particles that frequently are observed after LASIK. DESIGN: Small case series and
      experimental animal study. METHODS: Four patients received LASIK using a Schwind
      Supratome (Schwind, Kleinostheim, Germany) and a MEL 70 G-Scan excimer laser
      (Asclepion, Jena, Germany) and were examined over the course of 1 year using slit
      lamp and in vivo confocal microscopy. Four rabbits received a monocular
      microkeratome incision and were examined immediately after surgery without
      lifting the flap. After monthly evaluation for 4 months using in vivo confocal
      microscopy, 2 corneas were processed for histologic analysis and were sectioned
      serially. To measure the iron content, atomic absorption spectrometry was
      performed on 2 operated and 2 unoperated rabbit corneas. The chemical composition
      of the metal and plastic parts of the microkeratome blade was identified using
      energy dispersive x-ray fluorescence (metal part), and Raman and infrared
      spectroscopy (plastic part). Before and after oscillation in air, the
      microkeratome blade and motor-head were examined using light and fluorescence
      microscopy. In serial sections, interface particles were identified by
      fluorescence microscopy and their chemical composition was determined using
      Coherent Antistokes Raman Scattering microscopy. RESULTS: In LASIK patients,
      thousands of brightly reflecting particles (up to 30 micro m) were observed
      throughout the interface. The highest particle density was detected where the
      microkeratome blade had first entered the cornea. Both in the center and at the
      flap edge, the morphologic features, distribution, and density of these particles
      remained unaltered throughout the 1-year observation period. In rabbit corneas,
      interface particles were observed immediately after the microkeratome incision,
      even though the flap had not been lifted. These particles were similar to those
      observed in humans and persisted unaltered throughout the study. The operated and
      unoperated rabbit corneas had comparable iron content, demonstrating that the
      particles were not fragments of the uncoated steel blade. Only a few particles
      were observed on the unused microkeratome motor head and blade, whereas numerous
      fluorescent particles were detected after oscillation in air, the amount of
      particles increasing with oscillation time. Interestingly, the only fluorescent
      part of the microkeratome was the plastic segment of the blade. This plastic
      (polyetherimide) emitted fluorescence identical to that of the observed
      particles, whereas all metal parts of the microkeratome blade and motor head were
      nonfluorescent. In serial sections, interface particles showed fluorescent
      properties equivalent to polyetherimide and exhibited molecular resonance at 1780
      and 3100 cm(-1), in accordance with the Raman spectrum of polyetherimide.
      CONCLUSIONS: Numerous plastic particles are generated during microkeratome
      oscillation and are deposited at the interface during LASIK. The particles
      persist unaltered for at least 1 year.

PMID- 14711709
TI  - Proposed mechanism for retinal tears after LASIK: an experimental model.
AB  - OBJECTIVE: To demonstrate axial length changes associated with anterior shift of
      the lens/iris diaphragm and anterior vitreous base in human cadaver eyes during
      suction ring application preceding Moria LASIK, and to propose that these changes
      may be associated with anterior retinal tears. DESIGN: Human eye study.
      MATERIALS: Eight human eye bank eyes ranging in age from 65 to 73 years. Two eyes
      had a history of intraocular surgery involving cataract extraction and
      intraocular lens implantation. INTERVENTION: Measurements of intraocular pressure
      via internal manometer and Tono-Pen, anterior chamber depth, and axial length
      before and after application of a Moria LASIK suction ring. MAIN OUTCOME
      MEASURES: Change in anterior chamber depth and axial length after Moria LASIK
      suction ring application. RESULTS: Axial length increases (mean change = 1.125
      mm, P = 0.02) after application of the suction ring, whereas anterior chamber
      depth shows no significant difference (mean change = -0.01 mm, P = 0.98),
      suggesting anterior movement of the vitreous base resulting in traction on the
      anterior retina. CONCLUSION: Axial length increase with anterior displacement of
      the vitreous base during suction ring placement might predispose susceptible eyes
      to anterior retinal tears during and after LASIK.

PMID- 14711710
TI  - Linear-long incisions with a small optical zone for the correction of astigmatism
      in older patients.
AB  - PURPOSE: To evaluate the efficacy of astigmatic keratotomy (AK) by paired linear
      (transverse)-long incisions within a small optical zone in older patients with
      3.00 diopters (D) or more of astigmatism who are intolerant of contact lenses,
      spectacles, or both. DESIGN: Prospective, noncomparative case series.
      PARTICIPANTS: Twenty-one eyes (20 patients; age range, 58-87 years) treated at
      clinics of the Taipei Veterans General Hospital were included in this study.
      METHODS: Paired linear incisions (90 degrees in length) with a central optical
      zone (OZ) of 4.5 mm were made to correct high astigmatism in older patients. The
      incisions were 80% of the corneal thickness and parallel to the axis of the
      steepest cylinder. MAIN OUTCOME MEASURES: Refraction, keratometry, corneal
      topography, and visual acuity with and without correction were measured as the
      outcome indicators. RESULTS: The mean course of the stabilization of corneal
      curvature was 1.8 months. Significant improvement from a preoperative corneal
      astigmatism of 4.52+/-1.39 D to a postoperative value of 1.82+/-0.88 D (P<0.0001)
      was shown. Marked axis deviations of more than 30 degrees were observed in 5
      cases and corneal perforation was observed in 1 case. When the corneal curvature
      stabilized, uncorrected visual acuity was improved by 2 lines or more in 15 eyes
      (71.4%). Spherical equivalents and best-corrected visual acuity did not change
      significantly. Postoperative glare was absent in all patients. CONCLUSIONS: We
      conclude that AK by linear-long incisions extending from a small OZ is effective
      and safe for correcting astigmatism.

PMID- 14711711
TI  - Thygeson's superficial punctate keratitis: ten years' experience.
AB  - PURPOSE: To evaluate the presentation, treatment, and disease course of
      Thygeson's superficial punctate keratitis. DESIGN: Observational case series.
      PARTICIPANTS: Forty patients, diagnosed and managed with Thygeson's superficial
      punctate keratitis between January 1, 1992, and December 31, 2001, on the Cornea
      Service at Wills Eye Hospital. METHODS: Retrospective chart review. MAIN OUTCOME
      MEASURES: Patient demographics, symptoms, visual acuity, ophthalmic examination,
      management, duration of disease, and length of follow-up. RESULTS: At the time of
      presentation, the mean patient age was 28.7 years. The most common presenting
      symptoms included photophobia, blurred vision, and irritation. Thirty of 38
      patients without a history of decreased vision (78.9%) initially were seen with
      visual acuities in both eyes of 20/30 or better. The 8 (21.1%) remaining patients
      all had visual acuities between 20/40 and 20/50; improvement in vision with
      treatment was noted in all 3 observed at our institution. Six patients (16%) had
      unilateral disease, whereas another 2 patients had bilateral involvement develop
      after unilateral presentation. Thirty-nine patients (97.5%) were treated with
      topical steroids at some point in their disease course. The patient not managed
      with steroids was only seen once and was managed with artificial tears for mild
      symptoms. In addition to steroids, a patient was treated for recurrent episodes
      with extended-wear contact lens, and another patient was started on topical
      cyclosporine because of an inability to be tapered off topical steroids. The
      average duration of disease in the 15 patients who were observed for more than a
      single year was 11.1 years. CONCLUSIONS: Thygeson's superficial punctate
      keratitis is a potentially chronic condition, which might affect people of all
      ages for years to decades. Corticosteroids are the mainstay of treatment, with
      extended-wear contact lens and topical cyclosporine reserved as secondary agents.

PMID- 14711712
TI  - Donor source affects the outcome of ocular surface reconstruction in chemical or
      thermal burns of the cornea.
AB  - PURPOSE: To study the association between surgical approach and postoperative
      results in chemical and thermal burns of the cornea. DESIGN: Retrospective,
      interventional, noncomparable case series. PARTICIPANTS: Thirty-two eyes of 32
      patients with chemical (n = 27) or thermal (n = 5) burns of the cornea that were
      associated with total limbal dysfunction. Eight eyes had a history of previous
      keratoplasty. INTERVENTION: Patients were treated by amniotic membrane
      transplantation combined with either conjunctivolimbal autograft transplantation
      (autograft group, n = 11) or keratolimbal allograft transplantation (allograft
      group, n = 21). Fifteen eyes had simultaneous penetrating keratoplasty
      (simultaneous group), and 6 had keratoplasty several months after ocular surface
      reconstruction (2-step group). MAIN OUTCOME MEASURES: Reconstruction of the
      corneal surface by corneal epithelium, clarity of the cornea, and incidence of
      postoperative complications. The outcome was compared between the autograft and
      allograft groups and also between the simultaneous and 2-step groups. RESULTS: At
      final examination, 17 eyes (53.1%) showed stable corneal epithelialization.
      Preoperative conditions were similar in the autograft and allograft groups and
      also in the simultaneous and 2-step groups. The autograft group showed
      significantly better results than the allograft group in both corneal
      epithelialization (Kaplan-Meier analysis, P = 0.003) and clear cornea (P =
      0.010). Although the incidences of corneal epithelialization and clear corneas
      did not significantly differ between the simultaneous and 2-step groups, the
      former had a higher rate of endothelial rejection in the central graft (P =
      0.019). CONCLUSIONS: In chemical or thermal burns of the cornea with monocular
      involvement, autografting should be considered as a first choice of surgery. Even
      in eyes with opaque corneal stroma, it may be safer to perform ocular surface
      reconstruction first, followed by keratoplasty as a secondary procedure.

PMID- 14711713
TI  - Mucous membrane pemphigoid and pseudopemphigoid.
AB  - PURPOSE: To describe the clinical characteristics of patients with mucous
      membrane pemphigoid (MMP) and pseudopemphigoid. DESIGN: Retrospective cohort
      study. PARTICIPANTS: Two hundred eighty consecutive patients referred for the
      evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001.
      METHODS: Information on patients presenting for evaluation of possible MMP was
      entered prospectively into a database, which was supplemented by a retrospective
      chart review. Mucous membrane pemphigoid was diagnosed in patients with a
      compatible clinical picture by the linear deposition of antibodies to the
      basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous
      membrane biopsy specimen or by the presence of circulating autoantibodies to
      epithelial BMZ. MAIN OUTCOME MEASURES: Demographic and clinical characteristics
      of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with
      extraocular MMP without ocular disease. RESULTS: Among patients with ocular MMP,
      extraocular disease was common (82.4% of patients). The risk of ocular
      involvement among patients with MMP seen without ocular disease was approximately
      5% per year over the first 5 years of follow-up (cumulative risk at 5 years,
      22%). Although immunohistologic confirmation of the diagnosis was obtained in all
      patients, the initial conjunctival biopsy was positive for MMP in 80% of the
      patients diagnosed with ocular MMP. The most frequent presumed causes of
      pseudopemphigoid were topical glaucoma medications (28.3%), rosacea
      blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and
      conjunctival lichen planus (8.3%). CONCLUSIONS: Patients with ocular MMP
      typically have other systemic manifestations of MMP. Patients who are initially
      seen with extraocular MMP without ocular involvement are at risk for ocular
      disease developing. The clinical characteristics of ocular MMP and
      pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied
      tissue is needed to confirm the diagnosis of MMP.

PMID- 14711714
TI  - Prevalence and causes of visual impairment and blindness among 9980 Scandinavian
      adults: the Copenhagen City Eye Study.
AB  - PURPOSE: To investigate the age-specific prevalence and causes of visual
      impairment and blindness in an epidemiologic study of an adult Scandinavian
      population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: The
      study population was composed of 9980 persons, ages 20 to 84, from the general
      population of Copenhagen, Denmark. METHODS: This study is based on the third
      Copenhagen City Heart Study (CCHS III). Participants who reported visual
      impairment or blindness or had difficulty reading newspaper type and used
      prescribed eye medications were contacted from 1999 through 2000 and asked to
      complete a standardized interview concerning their ophthalmologic history.
      Verification of objective ophthalmologic data was done with a validated
      questionnaire response method. MAIN OUTCOME MEASURES: Best-corrected visual
      acuity in the better eye and primary causes of visual impairment and blindness.
      Visual impairment was defined as visual acuity worse than 20/40 but better than
      20/200, and blindness was defined as visual acuity of 20/200 or worse. RESULTS:
      The age-standardized prevalence rates of visual impairment and blindness were
      0.66% and 0.20%, respectively, and rose significantly with age (P<0.001). For
      persons 20 to 64 years, myopia-related retinal disorders, diabetic retinopathy,
      optic neuropathy, and retinitis pigmentosa were the most common causes of
      impaired vision. For persons 65 to 84 years, cataract was the most common cause
      of visual impairment, whereas age-related macular degeneration was the major
      cause of blindness. CONCLUSIONS: Visual impairment and blindness are strongly
      associated with increasing age, and the causes are determined by age. Among
      persons aged 20 to 64 years, an intervention for the predominating eye diseases
      might have some effect. Among those aged 65 to 84 years, cataract surgery could
      reduce visual impairment by one third.

PMID- 14711715
TI  - Prevalence and causes of visual impairment in an elderly Chinese population in
      Taiwan: the Shihpai Eye Study.
AB  - OBJECTIVE: Few population-based data on the prevalence and causes of visual
      impairment are available from East Asia. The purpose of this study was to
      determine the prevalence and causes of visual impairment in an elderly Chinese
      population in Taiwan. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: The Shihpai Eye Study was a survey of vision and ocular disease
      among an elderly Chinese population 65 years of age or older residing in Shihpai,
      Taiwan. A random sample of 2045 elderly residents was identified and selected
      from the household registration databank. Among them, 1361 (66.6%) underwent a
      detailed ophthalmic examination. METHODS: The ophthalmic examination included
      best-corrected visual acuity measurements using standardized protocols. Visual
      acuity was assessed with a Snellen E chart. The major cause of visual loss was
      identified for all participants who were visually impaired. MAIN OUTCOME
      MEASURES: Low vision and blindness were defined as a best-corrected visual acuity
      in the eye with better vision worse than 20/60 to a lower limit of 20/400 and
      worse than 20/400, respectively, according to World Health Organization
      categories of visual impairment. RESULTS: The mean age of the participants was
      72.2 (range, 65-91) years old. A total of 40 participants met the World Health
      Organization criteria of low vision, and 8 were diagnosed as blind. The rate of
      blindness and low vision was estimated to be 0.59% (95% confidence interval,
      0.25%, 1.16%) and 2.94% (95% confidence interval, 2.11%, 3.99%), respectively.
      There was a significant increase in the rate of low vision (P<0.001) from 0.83%
      at 65 to 69 years of age to 8.33% at age 80 years or older. There was no gender
      difference in the prevalence of blindness or low vision. The leading cause of
      visual impairment was cataract (41.7%), followed by myopic macular degeneration
      (12.5%) and age-related macular degeneration (10.4%). CONCLUSIONS: The rate of
      blindness and low vision is close to that reported for other developed countries.
      The high frequency of myopic macular degeneration as a major cause of visual
      loss, however, is not observed in European-derived populations. Specific
      prevention or low-vision rehabilitation programs should be developed for the
      elderly Chinese population.

PMID- 14711716
TI  - A case-control study of eye injuries in the workplace in Hong Kong.
AB  - OBJECTIVE: Eye injury in the workplace is common worldwide. This study proposed
      to explore both risk and preventive factors re eye injuries in Hong Kong. DESIGN:
      Case-control study. PARTICIPANTS: A total of 239 work-related eye injury
      patients, and 253 subjects without a history of any eye injury as controls.
      METHODS: Patients with all incident cases of work-related eye injuries attending
      the ophthalmology clinics of 3 major public hospitals in Hong Kong during the
      first 3 months of 2000 were invited to participate. Controls were selected from
      the general population and were frequency matched to patients based on gender.
      Patients were interviewed face-to-face by trained interviewers in the
      ophthalmology clinics, using a structured questionnaire. Telephone interviews
      were used for controls. MAIN OUTCOME MEASURES: Risk and protective factors
      associated with eye injuries. RESULTS: Among eye injury cases, 158 patients
      (66.1%) reported having incurred 1 episode of eye injury during employment, 49
      (20.5%) having suffered 2 episodes, and 32 (13.4%) having experienced >/=="
      BORDER="0">3 eye injuries at work. Most of the patients (85.4%) did not wear any
      protective devices at the time of injury. Subjects who wore safety glasses
      regularly were less likely to have eye injuries (odds ratio [OR] = 0.29, 95%
      confidence interval [CI] = 0.14-0.62). Having a safety requirement for wearing
      safety glasses was negatively associated with eye injuries (OR = 0.31, 95% CI =
      0.15-0.62). Multivariate analysis indicated that exposures to certain work
      hazards and working in the construction industry were positively associated with
      eye injuries. Subjects who worked longer in their current job, who reported
      having received job safety training before employment, or whose machines or
      equipment were maintained or repaired regularly by employers were at lower risk
      of experiencing eye injuries. CONCLUSIONS: Construction workers and those exposed
      to multiple hazards may get eye injuries at work. They should be provided with
      protective devices that are effective in preventing such exposures. Health
      education and safety training are important in preventing eye injuries.
      Maintenance and repair of machines and equipment may effectively reduce or
      eliminate the sources of exposures.

PMID- 14711717
TI  - Vitamin E supplementation and cataract: randomized controlled trial.
AB  - OBJECTIVE: To determine whether treatment with vitamin E (500 IU daily) reduces
      either the incidence or rate of progression of age-related cataracts. DESIGN: A
      prospective, randomized, double-masked, placebo-controlled clinical trial
      entitled the Vitamin E, Cataract and Age-Related Maculopathy Trial. PARTICIPANTS:
      Of 1906 screened volunteers, 1193 eligible subjects with early or no cataract,
      aged 55 to 80 years, were enrolled and followed up for 4 years. INTERVENTION:
      Subjects were assigned randomly to receive either 500 IU of natural vitamin E in
      soybean oil encapsulated in gelatin or a placebo with an identical appearance.
      MAIN OUTCOME MEASURES: The incidence and progression rates of age-related
      cataract were assessed annually with both clinical lens opacity gradings and
      computerized analysis of Scheimpflug and retroillumination digital lens images
      obtained with a Nidek EAS-1000 lens camera. The analysis was undertaken using
      data from the eye with the more advanced opacity for each type of cataract
      separately and for any cataract changes in each individual. RESULTS: Overall, 87%
      of the study population completed the 4 years of follow-up, with 74% of the
      vitamin E group and 76% of the placebo group continuing on their randomized
      treatment allocation throughout this time. For cortical cataract, the 4-year
      cumulative incidence rate was 4.5% among those randomized to vitamin E and 4.8%
      among those randomized to placebo (P = 0.87). For nuclear cataract, the
      corresponding rates were 12.9% and 12.1% (P = 0.77). For posterior subcapsular
      cataract, the rates were 1.7% and 3.5% (P = 0.08), whereas for any of these forms
      of cataract, they were 17.1% and 16.7%, respectively. Progression of cortical
      cataract was seen in 16.7% of the vitamin E group and 18.4% of the placebo group
      (P = 0.76). Corresponding rates for nuclear cataract were 11.4% and 11.9% (P =
      0.84), whereas those of any cataract were 16.5% and 16.7%, respectively. There
      was no difference in the rate of cataract extraction between the 2 groups (P =
      0.87). Lens characteristics of the participants withdrawn from the randomized
      medications were not different from those who continued. CONCLUSIONS: Vitamin E
      given for 4 years at a dose of 500 IU daily did not reduce the incidence of or
      progression of nuclear, cortical, or posterior subcapsular cataracts. These
      findings do not support the use of vitamin E to prevent the development or to
      slow the progression of age-related cataracts.

PMID- 14711718
TI  - Visual performance with multifocal intraocular lenses: mesopic contrast
      sensitivity under distance and near conditions.
AB  - OBJECTIVE: To evaluate distance and near visual performance under bright
      (photopic) and dim (mesopic) conditions in patients who had undergone
      uncomplicated cataract extraction with multifocal or monofocal intraocular lens
      (IOL) implantation. DESIGN: Prospective, nonrandomized, masked, comparative,
      observational case series. PARTICIPANTS: Thirty-two eyes of 32 patients after
      zonal-progressive multifocal IOL implantation (Allergan Medical Optics Array SA
      40N) and 32 eyes of 32 age-matched patients after monofocal IOL implantation
      (Allergan Medical Optics SI-40NB). INTERVENTION: All eyes underwent
      phacoemulsification and IOL implantation. MAIN OUTCOME MEASURES: At 18 months
      after surgery, the monocular contrast sensitivity (CS) function was measured with
      sinusoidal grating charts at distance and near, at one photopic luminance level
      and 2 mesopic luminance levels (85, 5, and 2.5 candelas per square meter).
      RESULTS: Under bright conditions, CS at distance in the multifocal group was not
      statistically different (P>0.01) from that in the monofocal group at any tested
      grating spatial frequency (1.5, 3, 6, 12, and 18 cycles per degree [cpd]). At low
      luminances, distance CS for the multifocal group was worse than that for the
      monofocal group at the highest test spatial frequencies (12 and 18 cpd; P<0.01).
      At near, photopic CS in the multifocal group was lower than at distance; patients
      with only a monofocal distance correction, however, could not detect the test
      gratings, even at the highest available contrast. With optimal near spectacle
      additions (i.e., using the distance correction of the multifocal IOL), there were
      no significant differences between the photopic near CS values for the multifocal
      and monofocal groups. When the luminance was decreased, near CS at all spatial
      frequencies was reduced in both groups. Contrast sensitivity in the near
      corrected, multifocal group was significantly worse than in the near-corrected,
      monofocal group at high spatial frequencies (12 and 18 cpd). CONCLUSIONS: This
      work supports the findings of earlier authors that the Array multifocal IOL, with
      its center-distance design, is distance biased. Distance CS is within normal
      limits under bright photopic conditions but shows deficits at higher spatial
      frequencies (more than approximately 12 cpd) under dim mesopic conditions. Near
      CS obtained with the multifocal IOL is below that which can be achieved by an
      appropriate monofocal near correction, for all spatial frequencies and
      illumination conditions.

PMID- 14711719
TI  - Factors associated with success in first-time trabeculectomy for patients at low
      risk of failure with chronic open-angle glaucoma.
AB  - PURPOSE: To examine the relationships between study factors and trabeculectomy
      outcome in a representative sample of United Kingdom ophthalmology surgeons and
      patients. DESIGN: Cross-sectional observational study by questionnaire.
      PARTICIPANTS: All ophthalmic surgeons performing trabeculectomy in the National
      Health Service were invited to select their 4 most recent consecutive
      trabeculectomy cases satisfying study eligibility criteria before June 1996.
      Three hundred eighty-two surgeons supplied baseline data for 1450 patients and 1
      year follow-up data for 1240 (85.3%) patients. All patients had undergone first
      time trabeculectomy for chronic open-angle glaucoma. METHODS: Data were collected
      by self-administered questionnaires at baseline and 6 and 12 months
      postoperatively. Univariate analysis of the relationships between study factors
      and success was performed by chi-square test (categorical variables) and
      Student's t or Mann-Whitney U tests (continuous variables). Multiple logistic
      regression modeling of explanatory variables significant at a P value of </=0.1
      was then performed. MAIN OUTCOME MEASURE: Trabeculectomy success, defined as a
      final intraocular pressure (IOP) less than two thirds of the preoperative IOP,
      excluding patients on antiglaucoma medications. RESULTS: After multiple logistic
      regression modeling, diabetes (odds ratio [OR] = 0.485, 95% confidence interval
      [CI] = 0.271-0.868, P = 0.015), superior rectus traction suture (OR = 0.580, 95%
      CI = 0.348-0.959, P = 0.034), subconjunctival anesthetic (OR = 0.172, 95% CI =
      0.065-0.459, P<0.0001), and nonspecialist surgeons (OR = 0.539, 95% CI = 0.335
      0.865, P = 0.010) remained significantly associated with poorer outcome.
      CONCLUSIONS: In this nationally representative sample of glaucoma patients
      undergoing first-time trabeculectomy, we have identified important associations
      between diabetes, superior rectus traction suture, subconjunctival anesthetic,
      nonspecialist surgeons, and diminished trabeculectomy success. These associations
      merit further examination.

PMID- 14711720
TI  - Long-term success of argon laser peripheral iridoplasty in the management of
      plateau iris syndrome.
AB  - OBJECTIVE: To document the long-term effect of argon laser peripheral iridoplasty
      (ALPI) in eyes with plateau iris syndrome. DESIGN: Retrospective, noncomparative,
      interventional case series. SETTING: New York Eye and Ear Infirmary. METHODS: The
      charts of all patients with plateau iris syndrome treated with ALPI from 1982 to
      1991 and subsequently followed for 6 or more years were retrospectively reviewed.
      Patients with lens-related mechanisms contributing to angle closure (e.g.,
      phacomorphic or malignant glaucoma) were excluded. MAIN OUTCOME MEASURES:
      Necessity for repeat ALPI and/or any additional means of intervention. RESULTS: A
      total of 26 ALPI procedures were performed in 23 eyes of 14 patients (4 men, 10
      women). The mean age was 61+/-8.7 years. The mean follow-up was 78.9+/-8.0 months
      (range, 72-188 months). The angle in 20 of 23 (87.0%) eyes remained open
      throughout the entire follow-up period after only 1 treatment with ALPI. In 3
      eyes, there was gradual reclosure of the angle 5 to 9 years after initial ALPI,
      but they were readily reopened and maintained open by a single repeat treatment.
      No filtration surgery was necessary in any eye during follow-up. CONCLUSIONS:
      ALPI is highly effective in eliminating residual appositional closure after laser
      iridotomy caused by plateau iris syndrome. The effect is maintained for years,
      although a small proportion of patients might require retreatment.

PMID- 14711721
TI  - Topiramate-associated acute, bilateral, secondary angle-closure glaucoma.
AB  - PURPOSE: To evaluate spontaneous reports of ocular side effects associated with
      topiramate use. DESIGN: Retrospective case series. METHODS: One hundred fifteen
      case reports, primarily of a specific ocular syndrome (acute secondary angle
      closure glaucoma), were collected from spontaneous reporting systems: the Drug
      Safety section of Ortho-McNeil Pharmaceuticals, Inc. (Raritan, NJ), the Food and
      Drug Administration (Rockville, MD), the World Health Organization (Uppsala,
      Sweden), the National Registry of Drug-Induced Side Effects (Casey Eye Institute,
      Oregon Health & Science University, Portland, Oregon), and the world literature.
      MAIN OUTCOME MEASURES: The data were evaluated using the World Health
      Organization Causality Assessment Guide to the certainty of a suspected adverse
      drug reaction. RESULTS: Eighty-six cases of acute-onset glaucoma (83 bilateral
      and 3 unilateral), 17 cases of acute bilateral myopia (up to 8.75 diopters), 9
      cases of suprachoroidal effusions, 3 cases of periorbital edema, and 4 cases of
      scleritis were reported. In those cases for which management was reported, 38%
      had laser or surgical peripheral iridectomy (21 cases). CONCLUSIONS: In the
      "certain" category of the World Health Organization classification system, the
      following are caused by topiramate therapy: abnormal vision, acute secondary
      angle-closure glaucoma, acute myopia, and suprachoroidal effusions. All findings
      are reversible if recognized early and if the drug is discontinued. The first
      presenting symptom of acute secondary angle-closure glaucoma in many patients was
      blurring of vision. Peripheral iridectomy is ineffective for this type of angle
      closure glaucoma.

PMID- 14711722
TI  - Surgical management of glaucoma in infants and children with Peters' anomaly:
      long-term structural and functional outcome.
AB  - OBJECTIVE: To determine the long-term outcome of surgery for congenital glaucoma
      in infants and children with Peters' anomaly. DESIGN: Retrospective review of a
      consecutive interventional case series. SETTING: An urban academic tertiary
      referral institution. PARTICIPANTS: Thirty-four eyes of 19 children are subjects
      of this report. Included are all children 12 years of age or younger with Peters'
      anomaly who underwent surgery for primary congenital glaucoma between January
      1971 and December 1992 and completed a minimum of 3 years of follow-up from the
      date of the first glaucoma surgery. INTERVENTION: The surgical procedures
      performed were trabeculectomy, trabeculotomy, goniotomy, Molteno shunt
      implantation, cyclodialysis, and cyclocryotherapy. MAIN OUTCOME MEASURES: Primary
      outcome measures were intraocular pressure (IOP) control and final postoperative
      visual acuity. Intraocular pressure control was defined as complete success
      (IOP</=21 mmHg without antiglaucoma medication), qualified success (IOP</=21 mmHg
      with antiglaucoma mediation), or failure (IOP>21 mmHg with or without
      antiglaucoma medication, inoperable retinal detachment, phthisis, or chronic
      hypotony, defined as an IOP of </=6 mmHg). RESULTS: A total of 126 glaucoma
      procedures were performed on 34 eyes of 19 patients. The median age at time of
      first glaucoma surgery was 2.1 months (range, 2 days to 8.5 years). The median
      follow-up was 11.0 years (range, 3.2 to 22.8 years) from the time of first
      glaucoma surgery. Intraocular pressure control with or without antiglaucoma
      medication was achieved in 11 eyes (32%) after 1 or more surgical procedures.
      Major postoperative complications included graft failure in 26 eyes (76%),
      cataract in 6 eyes (18%), inoperable retinal detachment with phthisis in 12 eyes
      (35%), and phthisis alone in 6 eyes (18%). Final vision was 20/200 or better in 3
      eyes (9%), 20/400 to hand motion in 12 eyes (35%), light perception in 7 eyes
      (21%), and no light perception in 12 eyes (35%). CONCLUSIONS: Glaucoma surgery,
      combined with medical therapy, may result in adequate, long-term IOP control in
      32% of eyes with glaucoma associated with Peters' anomaly. Visual results are
      poor due to uncontrolled glaucoma, amblyopia, neurologic impairment, and other
      anterior and posterior segment anomalies that may accompany Peters' anomaly.
      Postoperative complications, including graft failure, cataract, inoperable
      retinal detachment, and phthisis, also contribute to decreased visual acuity.

PMID- 14711723
TI  - Four-year incidence of visual impairment: Barbados Incidence Study of Eye
      Diseases.
AB  - OBJECTIVE: To describe the 4-year incidence of visual impairment and causes of
      blindness among black participants of the Barbados Eye Studies. DESIGN:
      Population-based incidence study. SETTING AND PARTICIPANTS: The Barbados
      Incidence Study of Eye Diseases (BISED) followed the cohort of the Barbados Eye
      Study (BES), a prevalence study based on a simple random sample of Barbadians 40
      to 84 years of age. BISED included 3193 black participants from the original
      cohort (85% of those eligible). MAIN OUTCOME MEASURES: Best-corrected visual
      acuity (Ferris-Bailey chart) at baseline and follow-up was measured according to
      a modified Early Treatment of Diabetic Retinopathy Study protocol. By use of
      World Health Organization (WHO) criteria, low vision and blindness for an
      individual were defined as visual acuity (VA) <6/18 to 6/120 and <6/120,
      respectively, in the better eye. By commonly used US criteria, low vision and
      blindness were defined as VA < or = 20/40 and < or = 20/200, respectively. Vision
      loss was defined as a doubling of the visual angle (i.e., decrease of 15 letters
      or more read correctly between baseline and follow-up examinations). Progression
      was defined as vision loss among those with low vision at baseline. RESULTS: On
      the basis of WHO criteria, the overall 4-year incidence was 3.6% (95% confidence
      interval [CI], 3.0%-4.4%) for low vision and 0.6% (95% CI, 0.4%-1.0%) for
      blindness. Incidence rates were higher using US criteria: 5.3% (95 % CI, 4.5%
      6.2%) and 1.5% (95% CI, 1.1%-2.0%), respectively, reaching 21.5% and 7.3% for
      persons aged 70 years or older at baseline. One tenth of the cohort had vision
      loss, and 28.6% of those with low vision progressed. About one half of incident
      blindness was due to age-related cataract. Nearly one fifth was caused by open
      angle glaucoma (OAG) alone or combined with cataract, and approximately 10% was
      caused by diabetic retinopathy (DR). CONCLUSIONS: The incidence of visual
      impairment was high in this Afro-Caribbean population, particularly in older age
      groups, indicating the public health significance of visual loss for this and
      similar black populations. Cataract, OAG, and DR were among the leading causes of
      incident blindness, paralleling their high prevalence in this population.

PMID- 14711724
TI  - What is lost by digitizing stereoscopic fundus color slides for macular grading
      in age-related maculopathy and degeneration?
AB  - OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized
      nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in
      age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN:
      Comparative observational case series. PARTICIPANTS: Twenty-five patients (50
      eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least
      1 eye were randomly selected from a large ongoing collection of clinical data and
      DNA in a tertiary referral United Kingdom population. Retinal photography was
      performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on
      Ektachrome slide transparency film. The images were centered on the macula. The
      color transparencies were then digitized. The grading process has been set up
      based on the International ARM Epidemiology Study Group. All images were
      independently graded by 3 retinal specialists. Both kappa statistics and exact
      agreement were calculated to assess agreement between and within observers and
      between the 2 master copies derived from the gradings of the color slides and
      digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies
      derived from the gradings obtained from stereoscopic slide transparencies and
      digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft
      drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93%
      (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the
      presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was
      94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93%
      (kappa, 0.78) for the area covered. For the presence of choroidal
      neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was
      95% (kappa, 0.83) for the area covered. For individual features of CNV, exact
      agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and
      2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because
      of the close agreement for most categories between the grading of stereoscopic
      color slides and digitized images, digitized nonstereoscopic color images prove
      to be useful for grading ARM and AMD.

PMID- 14711725
TI  - Intraocular pressure abnormalities associated with central and hemicentral
      retinal vein occlusion.
AB  - OBJECTIVE: To evaluate the prevalence of ocular hypertension (OHT) and glaucoma
      in patients with central retinal vein occlusion (CRVO) and hemi-CRVO (HCRVO) and
      of the fall in intraocular pressure (IOP) secondary to CRVO/HCRVO. DESIGN:
      Nonrandomized comparative case series. PARTICIPANTS AND METHODS: We investigated
      674 consecutive patients who were initially seen with unilateral CRVO (n = 548)
      and HCRVO (n = 126) at their onset, with a normal fellow eye. The fellow
      uninvolved eye in each patient acted as a control. Central retinal vein occlusion
      and HCRVO were categorized into nonischemic and ischemic. At all visits, patients
      had a detailed ocular history, as well as a thorough bilateral ocular evaluation,
      including IOP recording with a Goldmann applanation tonometer; when the diagnosis
      of OHT or glaucoma was initially uncertain, the 24-hour diurnal IOP was recorded.
      The observed prevalence rates of OHT and glaucoma among patients with CRVO and
      HCRVO were compared with those in the general population. MAIN OUTCOME MEASURES:
      The prevalence of OHT and glaucoma, and of ocular hypotension secondary to
      CRVO/HCRVO. RESULTS: The overall prevalence of glaucoma was 9.9% and of OHT
      16.2%. The prevalence of glaucoma/OHT was found to be significantly (P<0.0001)
      higher in patients with CRVO and HCRVO than in the general population. There was
      no significant difference in the proportion of patients with glaucoma/OHT among
      the various types of CRVO/HCRVO (P = 0.156). Forty-eight percent of all patients
      had lower IOP (>/==" BORDER="0">2 mmHg) in the CRVO/HCRVO eye than in the fellow
      (uninvolved) eye at their initial evaluation. The prevalence of ocular
      hypotension was significantly (P<0.0001) higher in patients with glaucoma/OHT not
      on ocular hypotensive therapy than in patients without glaucoma. Among the
      patients without glaucoma, the prevalence of ocular hypotension differed
      significantly among the various types of CRVO/HCRVO (P = 0.007). CONCLUSIONS:
      Central retinal vein occlusion and HCRVO have a significant association with
      glaucoma and OHT and with a subsequent fall in IOP in the involved eye. Few
      patients with CRVO/HCRVO have high IOP in the involved eye, although many of them
      do have it in the fellow uninvolved eye. It is important to exclude glaucoma/OHT
      in the fellow eye of any patient with CRVO/HCRVO; if present, elevated IOP should
      be treated to reduce the risk of that eye developing (1) CRVO/HCRVO and (2)
      glaucomatous damage. There may be no benefit to prescribing IOP-lowering drops
      for involved eyes whose IOP is already normal.

PMID- 14711726
TI  - Results of macular hole surgery with and without epiretinal dissection or
      internal limiting membrane removal.
AB  - PURPOSE: To evaluate the results of idiopathic macular hole surgery with or
      without epiretinal dissection or peeling of the internal limiting membrane (ILM).
      DESIGN: Retrospective consecutive nonrandomized comparative interventional trial.
      PARTICIPANTS: One hundred seventy-two eyes of 162 patients with previously
      untreated idiopathic macular holes of <24 months duration. INTERVENTION: All eyes
      were treated with pars plana vitrectomy by 1 surgeon using 1 of 3 techniques: no
      epiretinal dissection (116 eyes), epiretinal dissection (27 eyes), or ILM peeling
      (29 eyes). MAIN OUTCOME MEASURES: Closure of the macular hole and visual acuity.
      RESULTS: The macular hole was closed with 1 surgery in 92.9% of 56 eyes with
      epiretinal dissection/ILM peeling versus 79.3% of 116 eyes without dissection (P
      = 0.03) and was closed with 1 surgery in 85.1% of 27 eyes in the epiretinal
      dissection group compared with 100% of 29 eyes in the ILM peeling group (P =
      0.05). Visual acuity improved 3 or more lines in 57.1% of 56 eyes in the
      epiretinal dissection/ILM peeling group compared with 38.8% of 116 eyes in the no
      dissection group 3 months postoperatively (P = 0.03). Visual acuity improved 3 or
      more lines at 3 months in the no dissection group in 32.2% of 87 eyes placed
      faceup for 24 hours compared with 58.6% of 29 eyes placed immediately prone
      postoperatively (P = 0.02). The visual and anatomic results of the no dissection
      and epiretinal dissection/ILM peeling groups were similar when comparing eyes in
      the no dissection group placed immediately prone with the epiretinal
      dissection/ILM peeling eyes also placed immediately prone. Visual improvement of
      3 or more lines at 3 months occurred in 79.2% of 24 eyes in the epiretinal
      dissection group versus 44.8% of 29 eyes in the ILM peeling group (P = 0.01) in
      eyes with successful macular hole closure. Visual acuity results were similar in
      all subgroups at the final examination after reoperations. CONCLUSIONS: The
      faceup position for 24 hours using adjuvants reduced the initial anatomic and
      visual outcomes of macular hole surgery. Internal limiting membrane peeling
      improved the likelihood of successful macular hole closure but reduced the amount
      of initial visual improvement at 3 months compared with epiretinal dissection
      alone. Final visual acuities were similar in all groups.

PMID- 14711727
TI  - Salvage external beam radiotherapy of retinal capillary hemangiomas secondary to
      von Hippel-Lindau disease: visual and anatomic outcomes.
AB  - OBJECTIVE: To examine the visual and anatomic outcomes of patients with retinal
      capillary hemangiomas secondary to von Hippel-Lindau (VHL) disease treated with
      globe-salvaging fractionated external beam radiotherapy (EBRT) after progression
      of hemangiomas despite initial therapy. DESIGN: Retrospective noncomparative
      consecutive case series. PARTICIPANTS: Review of medical records of 5 patients
      with retinal capillary hemangiomas secondary to VHL disease. INTERVENTION:
      External beam radiotherapy delivered to a total dose of 2160 cGy given over 12
      daily fractions. MAIN OUTCOME MEASURES: Data on visual acuity and tumor size were
      collected at baseline, 1, 3, 6, and 12 months after EBRT, and at final follow-up,
      using echography, fundus photographs, and clinical examination. RESULTS: Six eyes
      of 5 patients were treated. Mean follow-up was 28.3 months (range, 6-51). Mean
      baseline visual acuity was 20/70. Mean visual acuity at last follow-up was 20/45
      (range, 20/25-20/60). Tumor volume reduction was 27.5 mm(3) (range, 0.9-109.6
      mm(3)). Mean percentage reduction in tumor volume was 39.6% (range, 3.3%-71.1%).
      CONCLUSIONS: External beam radiotherapy is a useful option in the treatment of
      retinal hemangiomas secondary to VHL disease that progress despite standard
      therapy. External beam radiotherapy leads to improvement in visual acuity,
      reduction in tumor volume, and stabilization of retinal detachment in most
      patients treated.

PMID- 14711728
TI  - Histopathology of eyes enucleated after endoresection of choroidal melanoma.
AB  - PURPOSE: To demonstrate the histopathologic features of eyes enucleated after
      endoresection for choroidal melanoma to assess the complications of this
      treatment and to determine indications for further treatment after endoresection
      in the setting of possible tumor recurrence. DESIGN: Retrospective, observational
      case series. PARTICIPANTS: Sixty-one consecutive patients who had undergone
      endoresection for uveal melanoma. METHODS: Eyes that had undergone enucleation
      after endoresection were identified, and their charts and histologic
      characteristics were reviewed. Pertinent features were described. One patient was
      excluded because enucleation was performed as a primary treatment when
      endoresection was abandoned at the time of his initial treatment. MAIN OUTCOME
      MEASURES: The outcome measures included: reasons for enucleation; tumor
      recurrence; and location, clinical, and histologic characteristics of each
      recurrence. RESULTS: Twelve eyes were identified that had undergone enucleation
      after endoresection. The reasons for enucleation were: (1) local tumor recurrence
      detected by ophthalmoscopy (2 patients) or echography (1 patient); (2) opaque
      media preventing adequate ophthalmoscopy (4 patients); (3) blind and painful eye
      of uncertain cause (1 patient); and (4) a combination of blind eye and limited
      fundus view (4 patients), which was the result of untreatable retinal detachment
      (3 patients) and endophthalmitis (1 patient). Eight of 12 patients had recurrent
      choroidal melanoma. Recurrences were all located adjacent to the resection site,
      although in 1 patient there was extensive diffuse recurrence throughout the eye.
      The recurrence was visible clinically in 3 patients and obscured because of
      opaque media (2 patients), a combination of inadequate echography and retinal
      detachment (1 patient), retinal detachment (1 patient), and endophthalmitis (1
      patient). CONCLUSIONS: Recurrent disease occurred at the site of the primary
      tumor with no seeding except in 1 patient, whose marginal recurrence was not
      immediately detected and treated because of opaque media. As with other
      treatments conserving the eye, enucleation should be performed if adequate ocular
      examination is not possible, and follow-up should be lifelong.

PMID- 14711730
TI  - Voluntary suppression of the multifocal electroretinogram.
AB  - OBJECTIVE: To describe multifocal electroretinogram (mfERG) responses in 2
      patients with nonorganic visual loss and in 11 eyes of 6 healthy persons who
      suppressed their mfERG responses. DESIGN: Observational case series. METHODS: The
      mfERG results were recorded in all individuals using the Veris Science 4.2
      instrument. All subjects were instructed to adjust the hexagonal test pattern so
      that it was in best focus. A second mfERG was recorded subsequently in volunteers
      who attempted suppression with inattention and poor fixation and by adjusting the
      focus to greatest blur. MAIN OUTCOME MEASURES: Amplitude and latency of mfERG
      responses. RESULTS: Suppressed mfERGs in patients with nonorganic visual loss and
      healthy volunteers demonstrated reduced amplitude, especially centrally.
      Amplitude reduction was statistically significant in the postsuppression as
      compared with the presuppression recordings in wave forms N1 and N2.
      Statistically significant shortening of postsuppression implicit times of P1 and
      N2 waveforms also was demonstrated. CONCLUSIONS: The mfERG responses may be
      suppressed voluntarily. Amplitude may be reduced. In contrast to most reported
      pathologic conditions, the implicit time is shortened.

PMID- 14711729
TI  - Normative data for a user-friendly paradigm for pattern electroretinogram
      recording.
AB  - PURPOSE: To provide normative data for a user-friendly paradigm for the pattern
      electroretinogram (PERG) optimized for glaucoma screening (PERGLA). DESIGN:
      Prospective nonrandomized case series. PARTICIPANTS: Ninety-three normal subjects
      ranging in age between 22 and 85 years. METHODS: A circular black-white grating
      of 25 degrees visual angle, reversing 16.28 times per second, was presented on a
      television monitor placed inside a Ganzfeld bowl. The PERG was recorded
      simultaneously from both eyes with undilated pupils by means of skin cup
      electrodes taped over the lower eyelids. Reference electrodes were taped on the
      ipsilateral temples. Electrophysiologic signals were conventionally amplified,
      filtered, and digitized. Six hundred artifact-free repetitions were averaged. The
      response component at the reversal frequency was isolated automatically by
      digital Fourier transforms and was expressed as a deviation from the age
      corrected average. The procedure took approximately 4 minutes. MAIN OUTCOME
      MEASURES: Pattern electroretinogram amplitude ( micro V) and phase (pi rad);
      response variability (coefficient of variation [CV] = standard deviation [SD] /
      mean x 100) of amplitude and phase of 2 partial averages that build up the PERG
      waveform; amplitude ( micro V) of background noise waveform, obtained by
      multiplying alternate sweeps by +1 and -1; and interocular asymmetry (CV of
      amplitude and phase of the PERG of the 2 eyes). RESULTS: On average, the PERG has
      a signal-to-noise ratio of more than 13:1. The CVs of intrasession and
      intersession variabilities in amplitude and phase are lower than 10% and 2%,
      respectively, and do not depend on the operator. The CV of interocular
      asymmetries in amplitude and phase are 9.8+/-8.8% and 1.5+/-1.4%, respectively.
      The PERG amplitude and phase decrease with age. Residuals of linear regression
      lines have normal distribution, with an SD of 0.1 log units for amplitude and
      0.019 log units for phase. Age-corrected confidence limits (P<0.05) are defined
      as +/-2 SD of residuals. CONCLUSIONS: The PERGLA paradigm yields responses as
      reliable as the best previously reported using standard protocols. The ease of
      execution and interpretation of results of PERGLA indicate a potential value for
      objective screening and follow-up of glaucoma.

PMID- 14711731
TI  - Prism adaptation in visually mature patients with esotropia of childhood onset.
AB  - OBJECTIVE: To investigate the role of prism adaptation in the visually mature
      population with esotropia onset before visual maturation. DESIGN: Retrospective,
      noncomparative case series. PARTICIPANTS: Eighty-five patients, 26 prism adapted
      for near (PAN) and 59 prism adapted for distance (PAD), were included in the
      study. METHODS: Patients included in this study were older than 9 years and had
      esotropia with an onset before age 9. Mean follow-up was 30 months (range = 6
      weeks-164 months). All patients had prism adaptation and subsequent surgical
      correction. Surgical success was defined as peripheral fusion on the Worth 4-dot
      test and < or = 8(Delta) deviation at near and distance on the simultaneous prism
      and cover test. MAIN OUTCOME MEASURES: Response to preoperative prism adaptation
      and postoperative alignment and sensory results were examined. RESULTS: Twenty
      six of the 85 patients had previous surgical esotropia correction. In the PAD
      group, 41 were responders. Seventeen of these had built their deviation > or =
      "0" > 10(Delta) with prism adaptation. All responders had surgery for their prism
      adapted angle. Postoperatively, 34 of 41 (83%) responders and 6 of 18 (33%)
      nonresponders had fusion. In the PAN group, 17 were responders. Nine of these
      built their deviation with prisms. Postoperatively, 16 of 17 (94%) responders and
      builders and 1 of 9 (11%) nonresponders had successful surgery with sensory and
      motor fusion. CONCLUSIONS: Adults with esotropia onset before visual maturation
      can be prism adapted and surgically treated with a predictable outcome of sensory
      and motor fusion. Those prism adapted for near with response can be successfully
      treated with surgery for the near deviation. Prism adaptation also aids in
      determining those who would benefit from larger amounts of surgery.

PMID- 14711732
TI  - Surgical treatment of trauma-induced periodic alternating nystagmus.
AB  - PURPOSE: To report a new treatment for acquired periodic alternating nystagmus in
      which medical therapy with baclofen was not tolerated. DESIGN: Interventional
      case report and literature review. INTERVENTION: Simultaneous adjustable
      bilateral retroequatorial horizontal rectus muscle recessions. MAIN OUTCOME
      MEASURES: Ocular alignment and ocular motility recordings. RESULTS: A 30-year-old
      man had blurred vision after an emergency left temporal craniotomy for gunshot
      wounds. Ophthalmologic examination revealed periodic alternating nystagmus that
      was documented by an infrared electronystagmogram. Baclofen was started but was
      not tolerated. Bilateral lateral and medial retroequatorial rectus muscle
      recessions were performed and were successful in the treatment of this patient.
      CONCLUSION: Simultaneous bilateral retroequatorial horizontal rectus recessions
      may be an effective treatment for intractable acquired periodic alternating
      nystagmus.

PMID- 14711733
TI  - Nonarteritic anterior ischemic optic neuropathy is associated with a specific
      platelet polymorphism located on the glycoprotein Ibalpha gene.
AB  - OBJECTIVE: To evaluate the association between platelet glycoprotein
      polymorphisms and the risks of single and second eye involvement with
      nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Case-control
      study. PARTICIPANTS: Ninety-two consecutive patients with NAION, 26 of whom had
      second eye involvement, and 145 controls who attended the eye clinic for
      nonvascular entities. METHODS: Polymerase chain reactions and restriction enzyme
      analyses were performed for genotyping 5 platelet glycoprotein polymorphisms on
      DNA extracted from whole blood. MAIN OUTCOME MEASURES: Frequencies of the various
      platelet polymorphisms. RESULTS: One of the 5 platelet glycoprotein polymorphisms
      analyzed, the B allele of the glycoprotein Ibalpha variable number of tandem
      repeats (VNTR), was a significant independent risk factor for NAION, with an odds
      ratio of 4.25 and a 95% confidence interval of 1.67 to 10.82 (P = 0.0026). All
      other platelet glycoprotein polymorphisms were similarly distributed in patients
      and controls. In addition, 9 of 16 patients who bore the VNTR B allele (56.3%)
      had second eye involvement, whereas among patients not harboring the VNTR B
      allele only 17 of 72 patients (23.6%) had second eye involvement (P = 0.009).
      Moreover, second eye involvement occurred earlier in patients who bore the
      specific polymorphism. CONCLUSIONS: The presence of the VNTR B allele of
      glycoprotein Ibalpha confers a significant risk for NAION and predisposes
      affected patients to second eye involvement.

PMID- 14711734
TI  - Two cases of orbital lymphangioma associated with vascular abnormalities of the
      retina and iris.
AB  - PURPOSE: To report 2 patients with combined intraocular and orbital vascular
      abnormalities. DESIGN: Two interventional case reports. MAIN OUTCOME MEASURES:
      Clinical and pathologic findings. INTERVENTION/TESTING: Orbitotomy, fluorescein
      angiography, magnetic resonance imaging, and radiation therapy. RESULTS: Two
      patients presented with vision loss, intermittent proptosis, and cosmetic
      deformity. These patients had orbital lymphangioma, ipsilateral retinal and iris
      vascular malformations, and smaller corneal diameter on the affected side.
      CONCLUSIONS: The coexistence of these diverse vascular anomalies supports the
      established hypothesis of pluripotential orbital vascular anlagen. Disruptive
      influences of various types during embryogenesis or development may produce a
      variety of congenital orbital and intraocular vascular malformations.

PMID- 14711735
TI  - A disagreement.

PMID- 14711737
TI  - Autograft for pterygia.

PMID- 14711739
TI  - Ultraviolet light and stem cells.

PMID- 14711740
TI  - Removal of a capsular tension ring.

PMID- 14711742
TI  - OAG in the visual impairment project.

PMID- 14711743
TI  - Infliximab treatment of posterior uveitis.

PMID- 14711744
TI  - Monitored anesthesia care.

PMID- 14711745
TI  - Monitored anesthesia care.

PMID- 14711747
TI  - Monitored anesthesia care.

PMID- 14711748
TI  - Cost effectiveness analysis of laparoscopic hysterectomy compared with standard
      hysterectomy: results from a randomised trial.
AB  - OBJECTIVE: To assess the cost effectiveness of laparoscopic hysterectomy compared
      with conventional hysterectomy (abdominal or vaginal). DESIGN: Cost effectiveness
      analysis based on two parallel trials: laparoscopic (n = 324) compared with
      vaginal hysterectomy (n = 163); and laparoscopic (n = 573) compared with
      abdominal hysterectomy (n = 286). PARTICIPANTS: 1346 women requiring a
      hysterectomy for reasons other than malignancy. MAIN OUTCOME MEASURE: One year
      costs estimated from NHS perspective. Health outcomes expressed in terms of QALYs
      based on women's responses to the EQ-5D at baseline and at three points during up
      to 52 weeks' follow up. RESULTS: Laparoscopic hysterectomy cost an average of 401
      pounds sterling (708 dollars; 571 euros) more (95% confidence interval 271 pounds
      sterling to 542 pounds sterling) than vaginal hysterectomy but produced little
      difference in mean QALYs (0.0015, -0.015 to 0.018). Mean differences in cost and
      QALYs generated an incremental cost per QALY gained of 267 333 pounds sterling
      (471 789 dollars; 380 437 euros). The probability that laparoscopic hysterectomy
      is cost effective was below 50% for a large range of values of willingness to pay
      for an additional QALY. Laparoscopic hysterectomy cost an average of 186 pounds
      sterling (328 dollars; 265 euros) more than abdominal hysterectomy, although 95%
      confidence intervals crossed zero (-26 pounds sterling to 375 pounds sterling);
      there was little difference in mean QALYs (0.007, -0.008 to 0.023), resulting in
      an incremental cost per QALY gained of 26 571 pounds sterling (46 893 dollars; 37
      813 euros). If the NHS is willing to pay 30 000 pounds sterling for an additional
      QALY, the probability that laparoscopic hysterectomy is cost effective is 56%.
      CONCLUSIONS: Laparoscopic hysterectomy is not cost effective relative to vaginal
      hysterectomy. Its cost effectiveness relative to the abdominal procedure is
      finely balanced.

PMID- 14711749
TI  - The eVALuate study: two parallel randomised trials, one comparing laparoscopic
      with abdominal hysterectomy, the other comparing laparoscopic with vaginal
      hysterectomy.
AB  - OBJECTIVE: To compare the effects of laparoscopic hysterectomy and abdominal
      hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal
      hysterectomy in the vaginal trial. DESIGN: Two parallel, multicentre, randomised
      trials. SETTING: 28 UK centres and two South African centres. PARTICIPANTS: 1380
      women were recruited; 1346 had surgery; 937 were followed up at one year. Primary
      outcome Rate of major complications. RESULTS: In the abdominal trial laparoscopic
      hysterectomy was associated with a higher rate of major complications than
      abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence
      interval 0.9% to 9.1%) and the number needed to treat to harm was 20.
      Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes)
      but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted
      in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks
      after the operation, laparoscopic hysterectomy was associated with less pain and
      better quality of life than abdominal hysterectomy (SF-12, body image scale, and
      sexual activity questionnaires). In the vaginal trial we found no evidence of a
      difference in major complication rates between laparoscopic hysterectomy and
      vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and
      the number needed to treat to harm was 333. We found no evidence of other
      differences between laparoscopic hysterectomy and vaginal hysterectomy except
      that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes)
      and was associated with a higher rate of detecting unexpected pathology (16.4% v
      4.8%, P = < 0.01). However, this trial was underpowered. CONCLUSIONS:
      Laparoscopic hysterectomy was associated with a significantly higher rate of
      major complications than abdominal hysterectomy. It also took longer to perform
      but was associated with less pain, quicker recovery, and better short term
      quality of life. The trial comparing vaginal hysterectomy with laparoscopic
      hysterectomy was underpowered and is inconclusive on the rate of major
      complications; however, vaginal hysterectomy took less time.

PMID- 14711750
TI  - Global burden of maternal death and disability.
AB  - Sound information is the prerequisite for health action: without data on the
      dimensions, impact and significance of a health problem it is neither possible to
      create an advocacy case nor to establish strong programmes for addressing it. The
      absence of good information on the extent of the burden of maternal ill-health
      resulted in its relative neglect by the international health community for many
      years. Maternal deaths are too often solitary and hidden events that go
      uncounted. The difficulty arises not because of lack of clarity regarding the
      definition of a maternal death, but because of the weakness of health information
      systems and consequent absence of the systematic identification and recording of
      maternal deaths. In recent years, innovative approaches to measuring maternal
      mortality have been developed, resulting in a stronger information base. WHO,
      UNICEF and UNFPA estimates for the year 2000 indicate that most of the total
      529,000 maternal deaths globally occur in just 13 countries. By contrast,
      information on the global burden of non-fatal health outcomes associated with
      pregnancy and childbearing remains patchy and incomplete. Nonetheless, initial
      estimates based on systematic reviews of available information and confined to
      the five major direct pregnancy-related complications indicate a problem of
      considerable magnitude.

PMID- 14711751
TI  - Safe motherhood: a brief history of the global movement 1947-2002.
AB  - The health of mothers has long been acknowledged to be a cornerstone of public
      health and attention to unacceptably high level of maternal mortality has been a
      feature of global health and development discussions since the 1980s. However,
      although a few countries have made remarkable progress in recent years, the
      reality has not generally followed the rhetoric. Health and development partners
      have failed to invest seriously in safe motherhood and examples of large-scale
      and sustained programmes are rare. Safe motherhood has tended to be seen as a
      subset of other programmes such as child survival or reproductive health and is
      often perceived to be too complex or costly for under-resourced and overstretched
      health care systems that have limited capacity. Despite this, a consensus has
      emerged about the interventions needed to reduce maternal mortality and there are
      good examples (historical and contemporary) of what can be achieved within a
      relatively short time period. The activities of both grassroots organizations and
      international health and development agencies have helped to build political will
      and momentum. Further progress in improving maternal health will require
      outspoken and determined champions from within the health system and the medical
      community, particularly the obstetricians and gynaecologists, and from among
      decision-makers and politicians. But in addition, substantial and long-term
      funding--by governments and by donor agencies--is an essential and still missing
      component.

PMID- 14711752
TI  - Beyond the numbers: reviewing maternal deaths and complications to make pregnancy
      safer.
AB  - Avoiding maternal deaths is possible, even in resource-poor countries, but
      requires the right kind of information on which to base programmes. Knowing the
      level of maternal mortality is not enough; we need to understand the underlying
      factors that led to the deaths. Each maternal death or case of life-threatening
      complication has a story to tell and can provide indications on practical ways of
      addressing its causes and determinants. Maternal death or morbidity reviews
      provide evidence of where the main problems in overcoming maternal mortality and
      morbidity may lie, produce an analysis of what can be done in practical terms and
      highlight the key areas requiring recommendations for health sector and community
      action as well as guidelines for improving clinical outcomes. The information
      gained from such enquiries must be used as a prerequisite for action.

PMID- 14711753
TI  - Skilled attendants for pregnancy, childbirth and postnatal care.
AB  - This paper sets out the rationale for ensuring that all pregnant women have
      access to skilled health care practitioners during pregnancy and childbirth. It
      describes why increasing access to a skilled attendant, especially at birth, is
      not only based on legitimate demand and clinical common sense, but is also cost
      effective and feasible in resource-poor countries. Skilled attendants need to be
      supported by a health system providing a legal and policy infrastructure, an
      effective referral system and the supplies that are necessary for effective care.
      A skilled attendant providing skilled care will help achieve the goals of
      reducing both maternal and child mortality. Health care professionals as
      individual practitioners, leaders and informers have an important role in making
      this a reality.

PMID- 14711754
TI  - Empowerment of women, men, families and communities: true partners for improving
      maternal and newborn health.
AB  - Based on the Health Promotion approach, the Making Pregnancy Safer initiative has
      proposed a strategic framework for working with individuals, families and
      communities to improve maternal and newborn health. The aims are to contribute to
      the empowerment of women, families and communities to increase their influence
      and control over maternal and newborn health, as well as to increase access to
      and utilization of quality skilled care. The framework has identified those
      strategies and interventions that target the factors known to contribute to
      health inequalities and poor maternal and newborn health. While empowerment is an
      aim of the framework, it is also considered a means. Emphasis is placed on the
      processes and the quality of the processes rather than just on the actions
      themselves. The authors in this paper would like to contribute to ongoing
      discussions about the 'how' of working with women, men, families and communities
      for improved maternal and newborn health.

PMID- 14711755
TI  - Promoting standards for quality of maternal health care.
AB  - Evidence-based health care with its emphasis on the need for searching,
      retrieving, summarizing and utilizing the best available evidence in decision
      making has become essential in setting standards. Accordingly, maternity care
      standards should be based on best available evidence identified through
      systematic reviews of the literature. Promotion of standards relies on access to
      information, active strategies to facilitate professional behaviour change and
      efforts to sustain the change. Access to information is essential but
      insufficient to improve standards on its own. Changing professional behaviour is
      not accomplished easily. Active strategies based on the nature of the health care
      problem and an evaluation of the barriers that are likely to operate against
      change are required to influence professional behaviour. Once implemented, the
      standards should be regularly monitored and revised as new evidence becomes
      available.

PMID- 14711756
TI  - Pregnancy--reducing maternal deaths and disability in Sri Lanka: national
      strategies.
AB  - The declining trend in the maternal mortality rate (MMR) from the 1930s to the
      late 1990s resulted from several strategies implemented within and outside the
      health sector. Expansion of both field-based and institutional services through
      the past decades contributed to improved geographical access and provision of
      'free' services improved economic access. These led to increased use of antenatal
      and natal services provided by trained midwives and other personnel followed by
      improvements in the availability of specialized care and emergency obstetric
      care. Integration of family planning and other inputs to the maternal health
      programme has yielded positive results. The role of the private sector is limited
      to provision of a component of antenatal services. The organization for service
      provision and an information system made significant contributions towards
      improvement. The commitment of the health sector to provide services free of
      charge supported by non-health inputs, especially female education, has enabled
      Sri Lanka to make gains in maternal health.

PMID- 14711757
TI  - Unsafe abortion: the silent scourge.
AB  - An estimated 19 million unsafe abortions occur worldwide each year, resulting in
      the deaths of about 70,000 women. Legalization of abortion is a necessary but
      insufficient step toward improving women's health. Without skilled providers,
      adequate facilities and easy access, the promise of safe, legal abortion will
      remain unfulfilled, as in India and Zambia. Both suction curettage and
      pharmacological abortion are safe methods in early pregnancy; sharp curettage is
      inferior and should be abandoned. For later abortions, either dilation and
      evacuation or labour induction are appropriate. Hysterotomy should not be used.
      Timely and appropriate management of complications can reduce morbidity and
      prevent mortality. Treatment delays are dangerous, regardless of their origin.
      Misoprostol may reduce the risks of unsafe abortion by providing a safer
      alternative to traditional clandestine abortion methods. While the debate over
      abortion will continue, the public health record is settled: safe, legal,
      accessible abortion improves health.

PMID- 14711758
TI  - Abortion: developments and impact in South Africa.
AB  - The article seeks to clarify the context of the Choice on Termination of
      Pregnancy Act, 1996 (Act No.92 of 1996), the factors that led to its adoption and
      implementation including the role of research in support of policy development,
      the expanded utilization of professional nurses, and the respect and promotion of
      women's right to life and well-being. The challenges that cropped up on the road
      to implementation and sustenance are also spelt out. It is important to evaluate
      the programme because this will assist South Africa to improve on the performance
      of service delivery. It will also assist other countries, both poor and rich, to
      progressively realize the promotion of human rights. Lastly, the article also
      seeks to identify areas that will lead to the improvement of women's lives, and
      ultimately societal development and health.

PMID- 14711759
TI  - Mothers infected with HIV.
AB  - The HIV/AIDS epidemic intersects with the problem of maternal mortality in many
      circumstances. The extent of the contribution of HIV/AIDS to maternal mortality
      is difficult to quantify, as the HIV status of pregnant women is not always
      known. HIV infection and AIDS-related deaths have become one of the major causes
      of maternal mortality in many resource-poor settings. HIV impacts on direct
      (obstetrical) causes of maternal mortality by an associated increase in pregnancy
      complications such as anaemia, post-partum haemorrhage and puerperal sepsis. HIV
      is also a major indirect cause of maternal mortality by an increased
      susceptibility to opportunistic infections such as Pneumocystis carinii
      pneumonia, tuberculosis and malaria. Appropriate antiretroviral therapy started
      in pregnancy could reverse the toll of HIV-related maternal mortality. Without
      such efforts and increased HIV prevention, the gains achieved by safe motherhood
      programmes will be lost in the future.

PMID- 14711760
TI  - Malaria prevention strategies.
AB  - Acute and severe consequences of pregnancy-associated malaria (PAM), such as
      materno-fetal death or cerebral malaria, seem limited to unstable malaria areas.
      In areas of stable endemicity, the main consequences are maternal anaemia and low
      birth weight (LBW) babies, particularly in primigravidae. Placental malaria seems
      more frequent and its consequences more severe in HIV-infected women. Since 1964,
      several chemoprophylaxis controlled trials have been undertaken, mainly in
      Tropical Africa where malaria is stable. Most showed an increase in mean birth
      weight in the prophylaxis group, especially among primigravidae. Similar findings
      were made with anaemia. Prophylaxis seems less effective in the case of HIV
      malaria co-infection, which may require an increase in the number of doses. At
      present, intermittent treatment with sulfadoxine-pyrimethamine given twice or
      thrice during pregnancy in antenatal clinics seems the best policy for preventing
      PAM. Such effective prophylaxis should be integrated with other antenatal clinic
      services. Recently identified molecular receptors involved in cytoadherence of
      parasitized erythrocytes to placenta could yield new therapeutic or vaccine
      approaches, specifically targeted to pregnant women.

PMID- 14711761
TI  - Anaemia and micronutrient deficiencies.
AB  - Anaemia in pregnancy is a common and worldwide problem that deserves more
      attention. For many developing countries, prevalence rates of up to 75% are
      reported. Anaemia is frequently severe in these situations and can be expected to
      contribute significantly to maternal mortality and morbidity. After a discussion
      of definitions, screening for anaemia and prevalence, the relationship between
      anaemia and maternal mortality and morbidity will be reviewed. Micronutrient
      deficiency and especially iron deficiency is believed to be the main underlying
      cause for anaemia. More recently the role of vitamin A deficiency as a
      contributing factor to anaemia has also been examined. The difficulties of
      assessment of micronutrient sufficiency or deficiency in pregnancy are described,
      as is the interaction between infection and micronutrient deficiency states.

PMID- 14711762
TI  - Pre-eclampsia and the hypertensive disorders of pregnancy.
AB  - Pre-eclampsia is a multisystem disorder, of unknown aetiology, usually associated
      with raised blood pressure and proteinuria. Although outcome for most women and
      their babies is good, it remains a major cause of morbidity and mortality. A wide
      range of interventions for prevention and treatment of pre-eclampsia have been
      evaluated in randomized trials. This evidence provides the basis for a rational
      approach to care. Overall, there is insufficient evidence for any firm conclusion
      about the effects of any aspect of diet or lifestyle during pregnancy.
      Antiplatelet agents are associated with a 19% reduction in the risk of pre
      eclampsia (relative risk 0.81; 95% CI 0.75, 0.88), a 7% reduction in the risk of
      preterm birth (RR 0.93; 95% CI 0.89, 0.98), a 16% reduction in the risk of
      stillbirth or neonatal death (RR 0.84; 95% CI 0.74, 0.96) and an 8% reduction in
      the risk of a small for gestational age baby (RR 0.92; 95% CI 0.85, 1.00). For
      mild to moderate hypertension, trials evaluating bed rest are too small for
      reliable conclusions about the potential benefits and hazards. Antihypertensive
      agents halve the risk of progression to severe hypertension (RR 0.52; 95% CI
      0.41, 0.64), but with no clear effect on pre-eclampsia (RR 0.99; 95% CI 0.84,
      1.18), or any other substantive outcome. For severe hypertension, there is no
      good evidence that one drug is any better than another. Plasma volume expansion
      for severe pre-eclampsia seems unlikely to be beneficial, although the trials are
      small. The optimum timing of delivery for pre-eclampsia before 34 weeks is
      unclear. Magnesium sulphate more than halves the risk of eclampsia (RR 0.41; 95%
      CI 0.29, 0.58) and probably reduces the risk of maternal death (RR 0.54; 95% CI
      0.26, 1.10). It is also the drug of choice for treatment of eclampsia.

PMID- 14711763
TI  - Thromboembolism.
AB  - Venous thomboembolism (VTE) causes only about 2% of maternal deaths in the
      developing world but is a leading cause of direct maternal deaths in developed
      countries. Pregnancy increases the risk of VTE through venous stasis, changes in
      blood coagulability and damage to vessels. Early diagnosis of VTE depends
      crucially on awareness of the condition but clinical diagnosis is unreliable in
      pregnancy and objective testing is essential. Compression or duplex
      ultrasonography is used to diagnose deep venous thrombosis and a
      ventilation/perfusion scan for pulmonary embolism. Low molecular weight heparins
      are safe and effective for treatment and for thromboprophylaxis in pregnancy. All
      women should undergo risk assessment in early pregnancy or preferably before
      pregnancy. Identifying risk factors such as obesity, or a past or family history
      of thromboembolism, allows at-risk women to be offered thromboprophylaxis.
      Guidelines on thromboprophylaxis have reduced deaths after caesarean section and
      are now being developed for all women.

PMID- 14711764
TI  - Obstructed labour.
AB  - Obstructed labour is an important cause of maternal deaths in communities in
      which undernutrition in childhood is common resulting in small pelves in women,
      and in which there is no easy access to functioning health facilities with the
      capability of carrying out operative deliveries. Obstructed labour also causes
      significant maternal morbidity in the short term (notably infection) and long
      term (notably obstetric fistulas). Fetal death from asphyxia is also common.
      There are differences in the behaviour of the uterus during obstructed labour,
      depending on whether the woman has delivered previously. The pattern in
      primigravid women (typically diminishing contractility with risk of infection and
      fistula) may result from tissue acidosis, whereas in parous women, contractility
      may be maintained with the risk of uterine rupture. Ultimately, tackling the
      problem of obstructed labour will require universal adequate nutritional intake
      from childhood and the ability to access adequately equipped and staffed clinical
      facilities when problems arise in labour. These seem still rather distant
      aspirations. In the meantime, strategies should be implemented to encourage early
      recognition of prolonged labour and appropriate clinical responses. The sequelae
      of obstructed labour can be an enormous source of human misery and the prevention
      of obstetric fistulas, and skilled treatment if they do occur, are important
      priorities in regions where obstructed labour is still common.

PMID- 14711765
TI  - Post-partum haemorrhage: definitions, medical and surgical management. A time for
      change.
AB  - Any woman who gives birth can have post-partum haemorrhage which may threaten her
      life. PPH is one of the leading causes of maternal mortality and an important
      cause for serious morbidity in the developing and developed world. We are at the
      threshold of major developments in its prevention and treatment due to changing
      ideas about its definition and medical and surgical management. The
      implementation of these changes is an essential part of a wider commitment
      towards saving mothers from complications of childbirth.

PMID- 14711766
TI  - Perinatal psychiatric disorders: a leading cause of maternal morbidity and
      mortality.
AB  - The Confidential Enquiry into Maternal Deaths 1997 to 1999 finds that psychiatric
      disorder, and suicide in particular, is the leading cause of maternal death.
      Suicide accounted for 28% of maternal deaths. Women also died from other
      complications of psychiatric disorder and a significant minority from substance
      misuse. Some of the findings of the Confidential Enquiry confirm long established
      knowledge about postpartum psychiatric disorder. The findings highlight the
      severity and early onset of serious postpartum mental illness and of the risk of
      recurrence following childbirth faced by women with a previous history of serious
      mental illness either following childbirth or at other times. These findings led
      to the recommendation that all women should be asked early in their pregnancy
      about a previous history of serious psychiatric disorder and that management
      plans should be in place with regard to the high risk of recurrence following
      delivery. Other findings of the Enquiry were new and challenged some of the
      accepted wisdoms of obstetrics and psychiatry. It is likely that the suicide rate
      following delivery is not significantly different to other times in women's lives
      and for the first 42 days following delivery may be elevated. This calls into
      question the so-called 'protective effect of maternity'. The overwhelming
      majority of the suicides died violently, contrasting with the usual finding that
      women are more likely to die from an overdose of medication. Compared to other
      causes of maternal death, the suicides were older and socially advantaged. The
      Enquiry findings suggest that the risk profile for women at risk of suicide
      following delivery may be different to that in women at other times and in men.
      None of the women who died had been admitted at any time to a Mother and Baby
      Unit and their psychiatric care had been undertaken by General Adult Services.
      None of the women who died had had a previous episode correctly identified and
      none had had adequate plans for their proactive care. The conclusion is that
      there is a need for both Psychiatry and Obstetrics to acknowledge the substantial
      risk that women with a previous psychiatric history of serious mental illness
      face following delivery.

PMID- 14711767
TI  - Near misses: a useful adjunct to maternal death enquiries.
AB  - In developed countries where maternal death is rare, the factors surrounding the
      death are often peculiar to the event and are not generalizable, making analysis
      of maternal deaths less useful. Near misses are defined as pregnant women with
      severe life-threatening conditions who nearly die but, with good luck or good
      care, survive. Incorporation of near misses into maternal death enquiries would
      strengthen these audits by allowing for more rapid reporting, more robust
      conclusions, comparisons to be made with maternal deaths, reinforcing lessons
      learnt, establishing requirements for intensive care and calculating comparative
      indices. The survival of a pregnant woman is dependent on the disease, her basic
      health, the health care facilities and personnel of the health care system. The
      criteria currently used to identify a near miss vary greatly. However, areas with
      similar health care facilities, medical records and personnel should be able to
      agree on suitable criteria, making their incorporation into maternal death
      enquiries feasible.

PMID- 14711770
TI  - Nobel Prize recognizes decades of sustained development in MRI.

PMID- 14711771
TI  - Implementation of IMRT in the radiotherapy department.
AB  - This paper describes the implementation of intensity modulated radiotherapy
      (IMRT) in a radiotherapy department. When preparing to set-up an IMRT programme,
      it is important to review departmental protocols with regard to immobilization,
      CT planning, treatment planning and verification. Any additional quality
      assurance steps also need to be fully understood. A new IMRT programme is most
      likely to be successful if it builds on established clinical experience with
      three-dimensional conformal radiotherapy (CRT). Training of radiographers,
      clinicians and physicists is critical, and both team-work and communication are
      vital to ensure a smooth transition from 3DCRT to IMRT delivery in the clinic.

PMID- 14711772
TI  - State-of-the-art imaging of pancreatic neoplasms.
AB  - Pancreatic imaging with multidetector CT allows multiphase acquisition of thin
      slices in a single breath-hold and is especially valuable in obtaining isotropic
      three-dimensional reformations that improves our ability to provide accurate pre
      operative vascular mapping. Advanced MR technology allows faster imaging of
      pancreas, thus facilitating MR cholangiopancreatography. Use of tissue-specific
      MR contrast agents, endoscopic ultrasound and PET in pancreatic imaging has
      evolved considerably. This review article discusses the role of CT, MR,
      endoscopic ultrasound and PET imaging in pancreas.

PMID- 14711773
TI  - Small "indeterminate" lesions on CT of the liver: a follow-up study of stability.
AB  - Distinguishing between small benign malformations in the liver and early
      metastatic disease remains difficult. We identified a group of 115 patients with
      known or suspected malignant disease who had "indeterminate" small liver lesions
      and who underwent 2-16 CT examinations (median 5) over a follow up period of 6-60
      months (median 16). The size, shape, edge, homogeneity and attenuation of each of
      these lesions was assessed. The lesions were classified by their behaviour on
      follow up CT as either stable (79%) or unstable (21%). The unstable lesions
      (n=62) included 37 that grew larger and 25 that became smaller or disappeared in
      patients undergoing anti-tumour therapy. Image features predictive of stable
      behaviour were small size and sharp edge. Heterogeneity and soft tissue
      attenuation were significantly associated with unstable behaviour, but these
      features were seen in only a small minority of cases. Shape had no predictive
      value. A logistic regression model was constructed based on size and edge to
      allow an estimate to be made of the likelihood of an individual lesion being
      unstable. In patients with known or suspected malignant disease, the majority of
      isolated small liver lesions found on CT are benign. Although size under 5 mm and
      a sharp margin are favourable features, this appearance does not exclude
      malignancy.

PMID- 14711774
TI  - Power Doppler ultrasound of rheumatoid synovitis: quantification of therapeutic
      response.
AB  - The aim of this study is to quantify power Doppler assessment of therapeutic
      response in rheumatoid synovitis. 13 patients (6 male, 7 female) with rheumatoid
      arthritis, who had an acute exacerbation of small joint synovitis in the hands,
      were examined with quantitative power Doppler, before and after intravenous
      corticosteroid treatment. All patients were examined by a single radiologist,
      using an ATL HDI 5000 ultrasound machine (ATL, Boswell). The images were analysed
      using a specially developed software package (HDI Lab), which quantifies power
      Doppler signal. All patients improved clinically following treatment, which was
      reflected in functional disability scores, and in the C-reactive protein levels
      and erythrocyte sedimentation rate. In all cases, there was a significant
      decrease in synovial vascularity as measured by the mean amplitude of signal on
      quantitative power Doppler. Quantitative power Doppler may allow objective
      assessment of treatment in small joint synovitis.

PMID- 14711775
TI  - Pulmonary lesions associated with Sjogren's syndrome: radiographic and CT
      findings.
AB  - The aim of this study was to analyse and compare the chest radiographic and CT
      findings in patients with primary and secondary Sjogren's syndrome. We
      retrospectively evaluated the frequency of abnormality and findings of both the
      chest radiography (n=107) and CT (n=59) in patients with Sjogren's syndrome.
      Abnormal cases were classified into five patterns based on predominant CT
      findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34
      (58%) patients, respectively. Most frequently observed abnormal findings were
      linear and reticular opacities on chest radiograph, and ground-glass opacity,
      interlobular septal thickening and intralobular interstitial thickening on CT in
      both primary and secondary Sjogren's syndrome. Centrilobular abnormalities were
      significantly more common in patients with primary Sjogren's syndrome (p=0.018).
      According to our CT classification, interstitial pneumonia (IP) pattern was the
      most common in patients with both primary and secondary Sjogren's syndrome.
      Bronchiolitis pattern was more common in patients with primary Sjogren's syndrome
      and lymphoproliferative disorder (LPD) pattern was only observed in primary
      Sjogren's syndrome. In conclusion, although the most frequently observed pattern
      in our CT classification was IP pattern in both primary and secondary Sjogren's
      syndrome, centrilobular abnormalities and LPD pattern were relatively
      characteristic in patients with primary Sjogren's syndrome.

PMID- 14711776
TI  - Evaluation of the Commission of the European Communities quality criteria for the
      paediatric lateral spine.
AB  - The study aimed to evaluate the Commission of the European Communities (CEC)
      quality criteria for paediatric lateral spine radiographs, and to use these to
      assess and compare the quality of film-screen and digital images. 286 paediatric
      lateral spine radiographs (89 film-screen and 197 digital) were independently
      analysed by two observers according to the CEC criteria. Based on fulfilment of
      criteria, images were assigned two scores, an image criteria score and a visual
      grading analysis score. Sensitivity values (S) on digital radiographs were
      recorded and correlated with image quality. Variability for assignment of scores
      between observers was lower for the image criteria than the visual grading
      analysis technique. Analysis of variance for fulfilment of criteria between
      techniques, and (for digital images) age and sensitivity values was calculated.
      Film-screen did significantly better (p<0.05) than digital imaging for Criterion
      6 (visually sharp reproduction of the cortex and trabecular markings consistent
      with age), but significantly worse for Criterion 7 (reproduction of the adjacent
      soft tissues). There was a significant difference in mean S values for each age
      group when Criterion 6 was or was not met. Results show that although
      interpretation between two observers was ambiguous, the CEC criteria were able to
      detect differences in quality of film-screen and digital images. It is also
      possible to use them when optimizing target S values.

PMID- 14711777
TI  - Calcification in coronary arteries as quantified by CT scans correlated with
      tobacco consumption in patients with inoperable non-small cell lung cancer
      treated with three-dimensional radiotherapy.
AB  - It has been shown that radiological manifestations of coronary artery sclerosis
      are an indirect measure of co-morbidity and predictive of survival. The aim of
      the present study is to evaluate the outcome and side effects after three
      dimensional (3D) radiotherapy in patients with unresectable non-small cell lung
      cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification,
      Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89
      patients with unresectable NSCLC were treated with 3D-radiotherapy. The median
      age was 66.6 years and median KI 80%. All patients had 3D-treatment planning,
      based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a
      week. The mean follow-up period was 13.2 months and mean survival time 12.2
      months. Significant prognostic factors for improved survival were KI and tumour
      stage. Patients with a KI<90% had a median survival of 6.5 months compared with
      14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II
      showed a significantly longer median survival than patients with NSCLC stage IIIA
      (16.5 months versus 7 months, p<0.004). A significant correlation was seen
      between pack-years and coronary artery calcification (p<0.05) and between age and
      marked coronary artery calcification. The incidence of calcification was 67% in
      smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years
      (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery
      calcification but correlated with chronic obstructive lung disease in 19/89
      patients. Conventional CT scans for 3D-treatment planning are able to detect
      coronary artery calcification. There is a significant correlation between age,
      KI, tobacco consumption and vascular calcification. Although there was a trend to
      worse overall survival, coronary artery calcification was not a significant
      predictor of progression-free and overall survival.

PMID- 14711778
TI  - A retrospective study of bladder morbidity in patients receiving intracavitary
      brachytherapy as all or part of their treatment for cervix cancer.
AB  - A retrospective study has been undertaken in an attempt to identify physical
      parameters that could confidently be used to predict an enhanced risk of bladder
      morbidity following intracavitary brachytherapy. 366 women received brachytherapy
      as all, or part, of their treatment for cervical cancer at the Christie Hospital
      in 1990 and 1991, and of these, 60 patients developed identifiable bladder
      morbidity (graded on a scale of 1-4 using the Franco-Italian glossary). These
      were age and stage matched with 60 asymptomatic women who were also treated for
      cervical cancer by brachytherapy during the same time period. The sizes of
      applicators used in the two groups were noted and compared. The two groups were
      also compared with respect to the heights of the applicator set above the
      symphysis pubis, the degree of anteversion or retroversion of the applicator sets
      and where possible, the doses at the International Commission on Radiation Units
      and Measurements (ICRU) bladder reference point. Where CT scans of the
      applications were available, these were reviewed to see if any differences in the
      size, shape or location of the bladder were apparent. No significant difference
      was found between the two groups of patients for any of the parameters
      investigated. The physical factors investigated in this study cannot be used to
      reliably predict bladder complications. There was a significant correlation
      between bladder morbidity and morbidity in other pelvic sites.

PMID- 14711779
TI  - A generic computer program for checking photon beam dose calculations.
AB  - A computer program for checking photon external beam dose calculations is
      described. It provides a check of the treatment planning calculation by the use
      of machine data that are independent of that used in the initial calculation.
      Data required to specify any radiation beam are easily and rapidly set up and the
      program works for all the major manufacturers' machines. The user interface uses
      an interactive screen for machine data input and also for dose checking, where
      dose calculation is performed in real time as data are entered. The dose
      resulting from the planned field parameters is calculated and compared with the
      prescribed dose with a warning provided if the agreement is outside a set range
      (+/-5%). Its purpose is to act as a final quality assurance check to ensure that
      no significant errors occur in the monitor unit calculation.

PMID- 14711780
TI  - Lower moiety pelvic-ureteric junction obstruction (PUJO) of the duplex kidney
      presenting with pyonephrosis in adults.
AB  - The most common congenital abnormality of the urinary tract is a duplex kidney.
      Pelvic-ureteric junction obstruction (PUJO) is a rare association that can affect
      the lower moiety of incomplete duplex kidneys. We report two adult cases of PUJO
      of the lower moiety in a duplex kidney that both presented with pyonephrosis.
      This late presentation of lower moiety PUJO with pyonephrosis has not been
      described previously. We describe the imaging appearances of this rare
      association and highlight this important diagnostic consideration in lower moiety
      hydronephrosis of the adult patient.

PMID- 14711781
TI  - Seed migration in prostate brachytherapy: a re-implant case report.
AB  - Seed embolisation to the lung is a possible risk following permanent prostate
      brachytherapy. The purpose of this work is to analyse a seed migration case and
      to suggest methods to reduce such occurrences. With this aim, the clinical
      history of the patient who experienced seed migration, the implant technique and
      the pre- and post-plan procedures have been investigated. The massive seed
      migration has been detected in the patient by means of a pelvic X-ray and a CT
      scan of the thorax. The use of loose seeds, the implant technique and the
      presence of unfavourable anatomical characteristics, have been recognised as
      possible causes of this event. The use of linked seeds embedded in vicryl sutures
      for the peripheral portions of prostate, and the development of an implant
      technique based on both transverse and longitudinal ultrasound guidance are
      proposed in order to reduce seed migration.

PMID- 14711782
TI  - Diffusion-weighted MRI and ADC mapping in FK506 neurotoxicity.
AB  - FK506 is a newly developed potent immunosuppressant for preventing rejection
      after organ transplantation. However, FK506 can induce central nervous system
      toxicity. Until now the pathogenic mechanism of FK506 neurotoxicity was unclear.
      We report the findings of diffusion-weighted MRI and apparent diffusion
      coefficient (ADC) mapping of a FK506 neurotoxicity patient who showed increased
      signal intensities in both parieto-occipital lobes on T(2) weighted images,
      diffusion-weighted images and ADC maps. These findings suggest that a vasogenic
      oedema rather than a cytotoxic oedema may play a pivotal role in FK506
      neurotoxicity pathogenesis.

PMID- 14711783
TI  - An unusual cause of respiratory symptoms in a toddler.

PMID- 14711785
TI  - Gold--now you see it, now you don't.

PMID- 14711786
TI  - Mutations in a novel locus on mouse chromosome 11 resulting in male infertility
      associated with defects in microtubule assembly and sperm tail function.
AB  - Traditional gene knock-out approaches using homologous recombination in embryonic
      stem cells are routinely used to provide functional information about genes
      involved in reproduction. In the present study, we examined a novel approach
      using N-ethyl-N-nitrosourea (ENU) together with a balancer chromosome mating
      strategy to identify new loci with functional roles in male fertility. Our
      genetic strategy is a forward-genetic approach; thus, our phenotypic
      investigation begins with the discovery of an abnormal phenotype without previous
      knowledge of the mutant locus. We isolated eight recessive mutations on
      chromosome 11 that resulted in male or female infertility from a screen of 184
      founder pedigrees from ENU-treated males. After testing the six male infertile
      and two female infertile mutations for their ability to complement, we found that
      three independent recessive male infertile mutations failed to complement each
      other. The male infertility was associated with reduced epididymal sperm count, a
      block in late-spermatid differentiation, and increased apoptosis. Furthermore,
      the three male infertile mutants had severe defects in epididymal sperm
      morphology associated with incorrect microtubule assembly. Electron microscopy
      revealed unique defects in sperm head and tail morphology for each of the three
      alleles. One allele had an abnormal manchette assembly of the sperm head. The
      other two alleles had different abnormalities in the 9+2 patterning of the
      microtubules in the sperm tail axoneme, with one containing only five of the
      microtubule doublets and the other containing an extra doublet. The isolation of
      this allelic series identifies a new locus on mouse chromosome 11 that is
      required for spermiogenesis and male fertility.

PMID- 14711787
TI  - Bicarbonate is required for migration of sperm epididymal protein DE (CRISP-1) to
      the equatorial segment and expression of rat sperm fusion ability.
AB  - Numerous studies have demonstrated that sperm capacitation is a bicarbonate
      dependent process. In the rat, capacitation has not been studied as much as in
      other species, mainly because of the difficulties in carrying out functional
      assays with this animal model. In the present study, we have examined the
      influence of bicarbonate in the overall rat sperm capacitation process by
      analyzing involvement of the anion in 1) protein tyrosine phosphorylation, 2)
      migration of epididymal protein DE (also known as CRISP-1) from the dorsal region
      to the equatorial segment of the sperm head that occurs during capacitation, and
      3) ability of sperm to fuse with the egg. Incubation of sperm under capacitating
      conditions produced a time-dependent increase in protein tyrosine
      phosphorylation. This phosphorylation did not occur in the absence of HCO3- and
      rapidly increased by either exposure of sperm to HCO3- or replacement of the
      anion by a cAMP analog (dibutyryl-cAMP) and a phosphodiesterase inhibitor
      (pentoxifylline). The absence of HCO3- also produced a significant decrease in
      the percentage of cells showing migration of DE to the equatorial segment. This
      parameter was completely restored by addition of the anion, but dibutyryl-cAMP
      and pentoxifylline were not sufficient to overcome the decrease in DE migration.
      Sperm capacitated in the absence of HCO3- were unable to penetrate zona-free eggs
      independent of the presence of the anion during gamete coincubation. Exposure of
      these sperm to bicarbonate, or replacement of the anion by dibutyryl-cAMP and
      pentoxifylline, only partially restored the sperm fusion ability. Altogether,
      these results indicate that, in addition to its influence on protein tyrosine
      phosphorylation, bicarbonate is required to support other rat sperm capacitation-
      associated events, such as migration of DE to the equatorial segment, and
      expression of the ability of sperm to fuse with the egg.

PMID- 14711788
TI  - Upregulation of steroidogenic enzymes and ovarian 17beta-estradiol in human
      granulosa-lutein cells by Cordyceps sinensis mycelium.
AB  - There is increasing evidence that 17beta-estradiol (E2) directly influences the
      quality of maturing oocytes and thus the outcome of assisted reproduction
      treatment. Although Cordyceps sinensis (CS) mycelium, a Chinese herbal medicine,
      is believed to enhance libido and fertility in both sexes, the mechanism of its
      effect in women has not been determined. The aim of the present study was to
      evaluate the effects of CS on steroidogenic enzyme expression and E2 biosynthesis
      in human granulosa-lutein cells (GLC). We found that CS induced E2 production by
      GLC in a dose- and time-dependent manner and that a 3-h treatment with CS induced
      increased levels of mRNAs coding for the P450 side chain cleavage enzyme
      (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and aromatase. Western
      blot analysis demonstrated that, after treatment with CS for 3 h, protein levels
      of steroidogenic acute regulatory protein (StAR) and aromatase were upregulated
      while P450scc and 3beta-HSD levels showed no substantial change. New protein
      synthesis was required for CS-induced E2 production because it was abrogated by
      cycloheximide pretreatment. Addition of 22(R)-hydroxycholesterol, thus bypassing
      the need for StAR protein, did not induce as much E2 production as CS treatment,
      indicating that upregulation of StAR protein was not the only factor contributing
      to CS-induced steroidogenesis. Cotreatment of GLCs with CS and aminoglutethimide,
      an aromatase inhibitor, completely abolished CS-induced E2 production. In
      conclusion, treatment of GLCs with CS results in increased E2 production due, at
      least in part, to increased StAR and aromatase expression. These data may help in
      the development of treatment regimens to improve the success rate of in vitro
      fertilization.

PMID- 14711789
TI  - The modulatory role of transforming growth factor beta1 and androstenedione on
      follicle-stimulating hormone-induced gelatinase secretion and steroidogenesis in
      rat granulosa cells.
AB  - To investigate the potential roles of matrix metalloproteinases (MMPs) in ovarian
      granulosa cell differentiation, we studied the interactive effects of FSH and
      local ovarian factors, transforming growth factor beta1 (TGFbeta1) and
      androstenedione, on gelatinase secretion and progesterone production in rat
      ovarian granulosa cells. Granulosa cells of eCG-primed immature rats were treated
      once with various doses of FSH and TGFbeta1 and androstenedione alone or in
      combinations for 2 days. Conditioned media were analyzed for gelatinase activity
      using gelatin-zymography/densitometry and progesterone levels using enzyme
      immunoassay. Cell lysates were analyzed for steroidogenic acute regulatory (StAR)
      and cholesterol side-chain-cleavage (P450scc) enzyme protein levels. This study
      demonstrates for the first time that FSH dose-dependently increased the secretion
      of a major 63-kDa gelatinase and minor 92- and 67-kDa gelatinases. TGFbeta1 also
      dose-dependently increased the secretion of 63-kDa gelatinase, while
      androstenedione alone had no effect. The 92-kDa gelatinase was identified as the
      pro-MMP9 that could be cleaved by aminophenylmercuric acetate into the 83-kDa
      active form. Importantly, we show that TGFbeta1 and androgen act in an additive
      manner to enhance FSH stimulatory effects both on the secretion of gelatinases
      and the production of progesterone. We further show by immunoblotting that the
      enhancing effect of TGFbeta1 and androstenedione on FSH-stimulated
      steroidogenesis is partly mediated through the increased level of StAR protein
      and/or P450scc enzyme. In conclusion, this study indicates that, during antral
      follicle development, TGFbeta1 and androgen act to enhance FSH promotion of
      granulosa cell differentiation and that the process may involve the interplay of
      modulating cell- to-matrix/cell-to-cell interaction and steroidogenic activity.

PMID- 14711790
TI  - Uterine androgen receptors: roles in estrogen-mediated gene expressionand DNA
      synthesis.
AB  - The localization of androgen receptors (AR) and their ligands in the uterine
      microenvironment at early pregnancy suggest a role for AR in uterine physiology.
      We have evaluated AR expression in the pig uterine endometrium and examined
      whether AR ligands modulate peri-implantation uterine gene expression. Northern
      blot analysis demonstrated the approximately 10.5 kilobase AR transcript in
      endometrium. Endometrial levels of AR mRNA and protein were greater at early than
      at mid- or late pregnancy. Estrogen receptor-alpha mRNA levels showed similar
      maximal expression at early pregnancy. Immunocytochemical analysis of endometrium
      at early pregnancy localized AR to nuclei of glandular epithelial (GE) and
      stromal (ST) cells. To evaluate a role for AR in uterine gene regulation, the
      levels of mRNAs for insulin-like growth factor-I (IGF-I), proliferative cell
      nuclear antigen (PCNA), and AR itself were assessed in uterine endometrial
      explant cultures treated with estradiol-17beta (E), testosterone (T), and 19
      nortestosterone (N). Induction by E of AR mRNA abundance occurred in endometrium
      from Day 10 but not from Day 12 pregnant animals and this was partially blocked
      by coaddition of N or T, although neither androgen alone had any effect.
      Abundance of IGF-I and PCNA mRNAs was increased by E and inhibited by coaddition
      of either T or N in Day 10 pregnant pig endometrium. In endometrium from Day 12
      pregnant animals, addition of either N or T with E increased IGF-I mRNA levels
      over that of controls, although E alone was without effect. In contrast, PCNA
      mRNA abundance was suppressed by all steroid treatments in these explants. DNA
      synthesis in primary cultures of GE cells from endometrium at Days 10 and 12 of
      pregnancy was increased by E and was suppressed by T, the latter only at Day 12.
      E did not affect DNA synthesis in ST cells from endometrium at either pregnancy
      day, although T inhibited this process in an E-dependent manner in ST cells from
      pregnancy Day 12. Results identify AR in the pig endometrium during the window of
      maternal receptivity for implantation and demonstrate the functional, albeit
      complex, interactions of androgens and estrogens in the regulation of uterine
      endometrial gene expression and cell growth in vitro. Further elucidation of the
      role of androgens and their receptor in early pregnancy events may be relevant to
      an understanding of peri-implantation embryo loss.

PMID- 14711791
TI  - Diethylstilbestrol versus estradiol as neonatal disruptors of the hamster
      (Mesocricetus auratus) cervix.
AB  - The synthetic estrogen diethylstilbestrol (DES) is an established, estrogenic
      endocrine disruptor (ED). The Syrian golden hamster (Mesocricetus auratus) offers
      some unique advantages as an experimental system to investigate the perinatal ED
      action of DES and other estrogenic EDs. Previous analyses regarding the
      consequences of neonatal administration (100 microg) of DES versus estradiol
      17beta (E2) showed that DES had a more potent disruptive effect on morphogenesis
      and gene expression in the uterus, oviduct, and ovary as well as in the testis
      and male accessory organs. The objectives of the present study were to describe
      the histopathological consequences of the two neonatal treatment regimens in the
      hamster cervix and to compare them with our previous observations in the hamster
      uterus. As previously found in the hamster uterus, DES was more potent than E2 as
      a neonatal disruptor of the hamster cervix in prepubertal animals and in ovarian
      intact adult animals. However, the cervix-versus-uterus scenario diverged in
      animals that were ovariectomized prepubertally and then chronically stimulated
      with natural estrogen (E2). We confirmed previous observations that neonatal
      exposure to DES, but not to E2, permanently alters estrogen responsiveness in the
      adult hamster uterus, but neither neonatal treatment regimen affected estrogen
      responsiveness in the adult hamster cervix. These results suggest that an
      unidentified ovarian factor influences the extent of neonatal DES-induced
      disruption of the cervix, but not of the uterus, in hamsters.

PMID- 14711792
TI  - Effect of cryopreservation methods and precryopreservation storage on bottlenose
      dolphin (Tursiops truncatus) spermatozoa.
AB  - Research was conducted to develop an effective method for cryopreserving
      bottlenose dolphin (Tursiops truncatus) semen processed immediately after
      collection or after 24-h liquid storage. In each of two experiments, four
      ejaculates were collected from three males. In experiment 1, three
      cryopreservation methods (CM1, CM2, and CM3), two straw sizes (0.25 and 0.5 ml),
      and three thawing rates (slow, medium, and fast) were evaluated. Evaluations were
      conducted at collection, prefreeze, and 0-, 3-, and 6-h postthaw. A sperm
      motility index (SMI; total motility [TM] x % progressive motility [PPM] x kinetic
      rating [KR, scale of 0-5]) was calculated and expressed as a percentage MI of the
      initial ejaculate. For all ejaculates, initial TM and PPM were greater than 85%,
      and KR was five. At 0-h postthaw, differences in SMI among cryopreservation
      methods and thaw rates were observed (P < 0.05), but no effect of straw size was
      observed. In experiment 2, ejaculates were divided into four aliquots for
      dilution (1:1) and storage at 4 degrees C with a skim milk- glucose or a N
      tris(hydroxymethyl)methyl-2-aminoethane sulfonic acid (TES)-TRIS egg yolk
      solution and at 21 degrees C with a Hepes-Tyrode balanced salt solution
      (containing bovine albumin and HEPES) (TALP) medium or no dilution. After 24 h,
      samples were frozen and thawed (CM3, 0.5-ml straws, fast thawing rate) at 20 x
      10(6) spermatozoa ml(-1) (low concentration) or at 100 x 10(6) spermatozoa ml(-1)
      (standard concentration). The SMI at 0-h postthaw was higher for samples stored
      at 4 degrees C than for samples stored at 21 degrees C (P < 0.001), and at 6-h
      postthaw, the SMI was higher for samples frozen at the standard concentration
      than for samples frozen at the low concentration (P < 0.05). For both
      experiments, acrosome integrity was similar across treatments. In summary, a
      semen cryopreservation protocol applied to fresh or liquid-stored semen
      maintained high levels of initial ejaculate sperm characteristics.

PMID- 14711793
TI  - Alpha-melanocyte-stimulating hormone inhibits lung injury after renal
      ischemia/reperfusion.
AB  - Combined acute renal and pulmonary failure has a very high mortality. In animals,
      lung injury develops after shock or visceral or renal ischemia. Alpha-melanocyte
      stimulating hormone (alpha-MSH) is an antiinflammatory cytokine, which inhibits
      inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury.
      We sought to determine if alpha-MSH inhibits acute lung injury after renal
      ischemia and to determine the early mechanisms of alpha-MSH action. Mice were
      subjected to renal ischemia treated with vehicle or alpha-MSH. At early time
      points, we measured organ histology, leukocyte accumulation, myeloperoxidase
      activity, activation of nuclear factor-kappaB, p38 mitogen-activated protein
      kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for
      intracellular adhesion molecule-1 and tumor necrosis factor-alpha. Renal ischemia
      rapidly activated kidney and lung nuclear factor-kappaB, p38 mitogen-activated
      protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury.
      Alpha-MSH administration immediately before reperfusion significantly decreased
      kidney and lung injury and prevented activation of kidney and lung transcription
      factors and stress response genes, and lung intracellular adhesion molecule-1 and
      tumor necrosis factor-alpha at early time points after renal
      ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after
      renal ischemia. alpha-MSH protects against both kidney and lung damage after
      renal ischemia, in part, by inhibiting activation of transcription factors and
      stress genes early after renal injury.

PMID- 14711794
TI  - Prospective study of acetaminophen use and newly diagnosed asthma among women.
AB  - Acetaminophen decreases glutathione levels in the lung, which may predispose to
      oxidative injury and bronchospasm. Acetaminophen use has been associated with
      asthma in cross-sectional studies and a birth cohort. We hypothesized that
      acetaminophen use would be associated with newly diagnosed adult-onset asthma in
      the Nurses' Health Study, a prospective cohort study of 121,700 women.
      Participants were first asked about frequency of acetaminophen use in 1990. Cases
      with asthma were defined as those with a new physician diagnosis of asthma
      between 1990 and 1996 plus reiteration of the diagnosis and controller medication
      use. Proportional hazard models included age, race, socioeconomic status, body
      mass index, smoking, other analgesic use, and postmenopausal hormone use. During
      352,719 person-years of follow-up, 346 participants reported a new physician
      diagnosis of asthma meeting diagnostic criteria. Increasing frequency of
      acetaminophen use was positively associated with newly diagnosed asthma (p for
      trend = 0.006). The multivariate rate ratio for asthma for participants who
      received acetaminophen for more than 14 days per month was 1.63 (95% confidence
      interval, 1.11-2.39) compared with nonusers. It would be premature to recommend
      acetaminophen avoidance for patients with asthma, but further research on
      pulmonary responses to acetaminophen is necessary to confirm or refute these
      findings and to identify subgroups whose asthma may be modified by acetaminophen.

PMID- 14711795
TI  - Fracture risk associated with inhaled corticosteroid use in chronic obstructive
      pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are frequently treated
      with inhaled corticosteroids (ICS). However, the impact of ICS use on fracture
      risk remains unclear in these patients. This nested case-control study examines
      the association between ICS use and nonvertebral fractures in Veterans Affairs
      patients with COPD. From a cohort of 40,157 patients with a COPD diagnosis
      between October 1, 1998 and September 30, 1999, and that used services in the
      preceding 12-month period but did not have a COPD diagnosis, 1,708 cases with
      nonvertebral fractures were identified and matched to 6,817 control patients.
      Patients were 94% male, and average age was 62.7 years. ICS exposure was
      identified through prescription records and converted to beclamethasone
      equivalents. In conditional logistic regression models, exposure to ICS at any
      time during follow-up was not associated with an increased fracture risk
      (adjusted odds ratio = 0.97; 95% confidence interval, 0.84-1.11). However,
      current high-dose ICS users (> or = 700 microg per day) had an increased risk of
      fractures compared with patients with no exposure (adjusted odds ratio = 1.68;
      95% confidence interval, 1.10-2.57). In patients with COPD, current use of high
      dose ICS was associated with an increased risk of nonvertebral fractures.

PMID- 14711796
TI  - Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and
      subjects with asthma.
AB  - Persistent airway inflammation is present in cases with asthma and in smokers
      with airflow obstruction. Isolated aggregations of lymphoid cells (IALC) may be
      sites of localized inflammatory cell activation. Their distribution and
      characteristics in cartilaginous airways were assessed in postmortem tissue from
      nonsmokers (n=10), smokers (n=9), and cases of nonfatal (n=10) and fatal asthma
      (n=10). IALC were present in 70-100% of cases, were more often in proximal than
      distal airways, and 80% were confined to the outer airway wall. IALC with area
      greater than 0.1 mm2 were more frequent in both asthma groups (p<0.001). Airways
      with IALC had increased airway dimensions and greater numbers of eosinophils and
      lymphomononuclear cells. Within IALC, T and B lymphocytes were segregated and
      comprised more than 90% of all cells. Proliferating, apoptotic, and antigen
      presenting cells (Rel B+ and HLA-DR+) were less than 5%, 30-40%, and less than 1%
      of all cells, respectively, and were similar in each case group. Vascular
      structures were increased (p < 0.01) in cases of fatal asthma. These findings
      show that, even in nonsmoking cases and cases without asthma, IALC are common,
      show cellular organization, and are associated with airway wall inflammation and
      remodeling. It remains to be determined if IALC contribute to or result from
      persistent airway inflammation in asthma.

PMID- 14711797
TI  - High tidal volume ventilation causes different inflammatory responses in newborn
      versus adult lung.
AB  - We investigated the effect of high VT ventilation on adult and newborn rats by
      examining pulmonary injury and cytokine messenger RNA (mRNA). On the basis of
      compliance, edema formation, and histology, ventilation with 25 ml.kg(-1) was
      more injurious to adult rats than newborns. Ventilation with 40 ml kg(-1)
      minimally affected compliance in newborns but caused death in adults. Ventilation
      of adults for 30 minutes at 25 ml kg(-1) upregulated the mRNA expression of
      interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), macrophage
      inflammatory protein-2 (MIP-2), and IL-10, whereas in newborns such ventilation
      only increased mRNA expression of MIP-2 and IL-10. When VT was raised to 40 ml
      kg(-1) in newborns, IL-1beta mRNA levels were additionally increased at 30
      minutes, whereas ventilation for 3 hours additionally increased IL-6 and TNF
      alpha mRNA. In newborns, the addition of 100% oxygen (O2) to 30 minutes of
      ventilation blunted the high VT induction of IL-1beta, IL-10, and MIP-2 mRNA
      expressions, whereas at 3 hours, 100% O2 concentration synergistically increased
      the mRNAs for TNF-alpha and IL-6. Overall, adult rats are more susceptible to
      high VT-induced lung injury compared with newborns. In newborns, the inflammatory
      response is dependent on VT, duration, and supplemental O2. Thus, recommendations
      for VT limitation based on adult data may be inappropriate for newborns.

PMID- 14711798
TI  - Evaluation of lung injury in rats and mice.
AB  - Lung injury is a broad descriptor that can be applied to conditions ranging from
      mild interstitial edema without cellular injury to massive and fatal destruction
      of the lung. This review addresses those methods that can be readily applied to
      rats and mice whose small size limits the techniques that can be practically used
      to assess injury. The methodologies employed range from nonspecific measurement
      of edema formation to techniques for calculating values of specific permeability
      coefficient for the microvascular membrane in lung. Accumulation of pulmonary
      edema can be easily and quantitatively measured using gravimetric methods and
      indicates an imbalance in filtration forces or restrictive properties of the
      microvascular barrier. Lung compliance can be continuously measured, and light
      and electron microscopy can be used regardless of lung size to detect edema and
      structural damage. Increases in fluid and/or protein flux due to increased
      permeability must also be separated from those due to increased filtration
      pressure for mechanistic interpretation. Although an increase in the initial lung
      albumin clearance compared with controls matched for size and filtration pressure
      is a reliable indicator of endothelial dysfunction, calculated alterations in
      capillary filtration coefficient K(f,c), reflection coefficient sigma, and
      permeability-surface area product PS are the most accurate indicators of
      increased permeability. Generally, PS and K(f,c) will increase and sigma will
      decrease with vascular injury, but derecruitment of microvascular surface area
      may attenuate the affect on PS and K(f,c) without altering measurements of sigma.

PMID- 14711799
TI  - On the sources of retinoic acid in the lung: understanding the local conversion
      of retinol to retinoic acid.

PMID- 14711800
TI  - The alveolar water gate.

PMID- 14711801
TI  - Overexpression of Smurf1 negatively regulates mouse embryonic lung branching
      morphogenesis by specifically reducing Smad1 and Smad5 proteins.
AB  - Early embryonic lung branching morphogenesis is regulated by many growth factor
      mediated pathways. Bone morphogenetic protein 4 (BMP4) is one of the morphogens
      that stimulate epithelial branching in mouse embryonic lung explant culture. To
      further understand the molecular mechanisms of BMP4-regulated lung development,
      we studied the biological role of Smad-ubiquitin regulatory factor 1 (Smurf1), an
      ubiquitin ligase specific for BMP receptor-regulated Smads, during mouse lung
      development. The temporo-spatial expression pattern of Smurf1 in mouse embryonic
      lung was first determined by quantitative real-time PCR and immunohistochemistry.
      Overexpression of Smurf1 in airway epithelial cells by intratracheal introduction
      of recombinant adenoviral vector dramatically inhibited embryonic day (E) 11.5
      lung explant growth in vitro. This inhibition of lung epithelial branching was
      restored by coexpression of Smad1 or by addition of soluble BMP4 ligand into the
      culture medium. Studies at the cellular level show that overexpression of Smurf1
      reduced epithelial cell proliferation and differentiation, as documented by
      reduced PCNA-positive cell index and by reduced mRNA levels for surfactant
      protein C and Clara cell protein 10 expression. Further studies found that
      overexpression of Smurf1 reduced BMP-specific Smad1 and Smad5, but not Smad8,
      protein levels. Thus overexpression of Smurf1 specifically promotes Smad1 and
      Smad5 ubiquitination and degradation in embryonic lung epithelium, thereby
      modulating the effects of BMP4 on embryonic lung growth.

PMID- 14711802
TI  - Resistance of differentiated human airway epithelium to infection by rhinovirus.
AB  - Virtually all in vitro studies of the effects of rhinovirus on human airway
      epithelium have used cells grown under conditions known to produce low levels of
      differentiation. The relevance of the results to native epithelium is
      questionable. Here we grew primary cultures of human tracheal or nasal epithelium
      under three conditions. One condition produced pseudostratified, mucociliary
      cells virtually indistinguishable from native epithelium. The other two
      conditions produced undifferentiated squamous cells lacking cilia. Cells were
      infected for 6 h with rhinovirus-16. After a 24-h incubation period, we
      determined levels of viral RNA in the cells, numbers of infectious viral
      particles released in the mucosal medium, expression of a variety of epithelial
      cytokines and other proteins, release of IL-6 and IL-8, and transepithelial
      electrical resistance and voltage. After infection, levels of viral RNA in the
      poorly differentiated cells were 30 or 130 times those in the differentiated.
      Furthermore, expression of mRNA for inflammatory cytokines, release of infectious
      particles, and release of IL-6 and IL-8 were closely correlated with the degree
      of viral infection. Thus well-differentiated cells are much more resistant to
      viral infection and its functional consequences than are poorly differentiated
      cells from the same source.

PMID- 14711803
TI  - Inhibition of CLC-2 chloride channel expression interrupts expansion of fetal
      lung cysts.
AB  - Normal lung morphogenesis is dependent on chloride-driven fluid transport. The
      molecular identity of essential fetal lung chloride channel(s) has not been
      elucidated. CLC-2 is a chloride channel, which is expressed on the apical surface
      of the developing respiratory epithelium. CLC-2-like pH-dependent chloride
      secretion exists in fetal airway cells. We used a 14-day fetal rat lung
      submersion culture model to examine the role of CLC-2 in lung development. In
      this model, the excised fetal lung continues to grow, secrete fluid, and become
      progressively cystic in morphology (26). We inhibited CLC-2 expression in these
      explants, using antisense oligonucleotides, and found that lung cyst morphology
      was disrupted. In addition, transepithelial voltage (V(t)) of lung explants
      transfected with antisense CLC-2 was inhibited with V(t) = -1.5 +/- 0.2 mV (means
      + SE) compared with -3.7 +/- 0.3 mV (means + SE) for mock-transfected controls
      and -3.3 +/- 0.3 mV (means + SE) for nonsense oligodeoxynucleotide-transfected
      controls. This suggests that CLC-2 is important for fetal lung fluid production
      and that it may play a role in normal lung morphogenesis.

PMID- 14711804
TI  - Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal
      defect that is associated with vitamin A deficiency.
AB  - Airway hyperresponsiveness (AHR) is influenced by structural components of the
      bronchial wall, including the smooth muscle and connective tissue elements and
      the neuromuscular function. AHR is also influenced by parenchymally derived
      tethering forces on the bronchial wall, which maintain airway caliber by
      producing outward radial traction. Our previous work has shown that vitamin A
      deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in
      the expression and function of the muscarinic-2 receptors (M2R). We hypothesized
      that if decreases in radial traction from airway or parenchymal structures
      contributed to the VAD-related increase in AHR, then the radial traction would
      normalize more slowly than VAD-related alterations in neurotransmitter signaling.
      Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained
      on the VAD diet in the presence or absence of supplementation with all-trans
      retinoic acid (RA). VAD was associated with an approximately twofold increase in
      respiratory resistance and elastance compared with VAS rats. Exposure to RA for
      12 days but not 4 days restored resistance and elastance to control (VAS) levels.
      In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression
      and function, which were restored after 12 days of RA supplementation.
      Subepithelial bronchial elastic fibers were decreased by approximately 50% in VAD
      rats and were significantly restored by RA. The increase in AHR that is
      associated with VAD is accompanied by decreases in M2R expression and function
      that can be restored by RA and a reduction in airway elastic fibers that can be
      partially restored by RA.

PMID- 14711809
TI  - Isolation and characterization of a HpyC1I restriction-modification system in
      Helicobacter pylori.
AB  - Using transposon shuttle mutagenesis, we identified six Helicobacter pylori
      mutants from the NTUH-C1 strain that exhibited decreased adherence and cell
      elongation. Inverse polymerase chain reaction and DNA sequencing revealed that
      the same locus was interrupted in these six mutants. Nucleotide and amino acid
      sequences showed no homologies with H. pylori 26695 and J99 strains. This novel
      open reading frame contained 1617 base pairs. The amino acid sequence shared 24%
      identity with a putative nicking enzyme in Bacillus halodurans and 23 and 20%
      identity with type IIS restriction endonucleases PleI and MlyI, respectively. The
      purified protein, HpyC1I, showed endonuclease activity with the recognition and
      cleavage site 5'-CCATC(4/5)-3'. Two open reading frames were located upstream of
      the gene encoding HpyC1I. Together, HpyC1I and these two putative
      methyltransferases (M1.HpyC1I and M2.HpyC1I) function as a restriction
      modification (R-M) system. The HpyC1I R-M genes were found in 9 of the 15 H.
      pylori strains tested. When compared with the full genome, significantly lower G
      + C content of HpyC1I R-M genes implied that these genes might have been acquired
      by horizontal gene transfer. Plasmid DNA transformation efficiencies and
      chromosomal DNA digestion assays demonstrated protection from HpyC1I digestion by
      the R-M system. In conclusion, we have identified a novel R-M system present in
      approximately 60% of H. pylori strains. Disruption of this R-M system results in
      cell elongation and susceptibility to HpyC1I digestion.

PMID- 14711810
TI  - Ligand-induced, p38-dependent apoptosis in cells expressing high levels of
      epidermal growth factor receptor and ErbB-2.
AB  - Increased expression of the epidermal growth factor (EGF) receptor (EGFR) and
      ErbB-2 is implicated into the development and progression of breast cancer.
      Constant ligand-induced activation of EGFR and ErbB-2 receptor-tyrosine kinases
      is thought to be involved in the transformation of fibroblasts and mammary
      epithelial cells. Data herein show that ligand stimulation of cells that express
      both the EGFR and the ErbB-2 may result either in cell proliferation or apoptosis
      depending on the expression levels of EGFR and ErbB-2. Mammary tumor cells that
      express low levels of both receptors or high levels of ErbB-2 and low levels of
      EGFR survive and proliferate in the presence of EGF. In contrast, fibroblastic
      cells or mammary tumor cells, which co-express high levels of EGFR and ErbB-2
      invariably undergo apoptosis in response to EGF. In these cells persistent
      activation of p38 MAPK is an essential element of the apoptotic mechanism. Also,
      the data implicate a p38-dependent change in mitochondrial membrane permeability
      as a downstream effector of apoptosis. Ligand-dependent apoptosis in cells co
      expressing high levels of EGFR and ErbB-2 could be a natural mechanism that
      protects tissues from unrestricted proliferation in response to the sustained
      activation of receptor-tyrosine kinases.

PMID- 14711811
TI  - Flexibility at Gly-194 is required for DNA cleavage and relaxation activity of
      Escherichia coli DNA topoisomerase I.
AB  - The proposed mechanism of type IA DNA topoisomerase I includes conformational
      changes by the single enzyme polypeptide to allow binding of the G strand of the
      DNA substrate at the active site, and the opening or closing of the "gate"
      created on the G strand of DNA to the passing single or double DNA strand(s)
      through the cleaved G strand DNA. The shifting of an alpha helix upon G strand
      DNA binding has been observed from the comparison of the type IA DNA
      topoisomerase crystal structures. Site-directed mutagenesis of the strictly
      conserved Gly-194 at the N terminus of this alpha helix in Escherichia coli DNA
      topoisomerase I showed that flexibility around this glycine residue is required
      for DNA cleavage and relaxation activity and supports a functional role for this
      hinge region in the enzyme conformational change.

PMID- 14711812
TI  - Dual mechanisms for shedding of the cellular prion protein.
AB  - The cellular prion protein (PrP(C)) is essential for the pathogenesis and
      transmission of prion diseases. Whereas the majority of PrP(C) is bound to the
      cell membrane via a glycosylphosphatidylinositol (GPI) anchor, a secreted form of
      the protein has been identified. Here we show that PrP(C) can be shed into the
      medium of human neuroblastoma SH-SY5Y cells by both protease- and phospholipase
      mediated mechanisms. The constitutive shedding of PrP(C) was inhibited by a range
      of hydroxamate-based zinc metalloprotease inhibitors in a manner identical to the
      alpha-secretase-mediated shedding of the amyloid precursor protein, indicating a
      proteolytic shedding mechanism. Like amyloid precursor protein, this zinc
      metalloprotease-mediated shedding of PrP(C) could be stimulated by phorbol
      myristate acetate and by copper ions. The lipid raft-disrupting agents filipin
      and methyl-beta-cyclodextrin promoted the shedding of PrP(C) via a distinct
      mechanism that was not inhibited by hydroxamate-based inhibitors. Filipin
      mediated shedding of PrP(C) is likely to occur via phospholipase cleavage of the
      GPI anchor, since a transmembrane polypeptide-anchored PrP construct was not shed
      in response to filipin treatment. Collectively, our data indicate that shedding
      of PrP(C) can occur via both secretase-like proteolytic cleavage of the protein
      and phospholipase cleavage of the GPI anchor moiety.

PMID- 14711813
TI  - Identification of RET autophosphorylation sites by mass spectrometry.
AB  - The catalytic and signaling activities of RET, a receptor-type tyrosine kinase,
      are regulated by the autophosphorylation of several tyrosine residues in the
      cytoplasmic region of RET. Some studies have revealed a few possible
      autophosphorylation sites of RET by [(32)P]phosphopeptide mapping or by using
      specific anti-phosphotyrosine antibodies. To ultimately identify these and other
      autophosphorylation sites of RET, we performed mass spectrometry analysis of an
      originally prepared RET recombinant protein. Both the autophosphorylation and
      kinase activity of myelin basic protein as an external substrate of the
      recombinant RET protein were substantially elevated in the presence of ATP
      without stimulation by a glial cell line-derived neurotrophic factor, a natural
      ligand for RET. Mass spectrometric analysis revealed that RET Tyr(806), Tyr(809),
      Tyr(900), Tyr(905), Tyr(981), Tyr(1062), Tyr(1090), and Tyr(1096) were
      autophosphorylation sites. Levels of autophosphorylation and kinase activity of
      RET-MEN2A (multiple endocrine neoplasia 2A), a constitutively active form of RET
      with substitution of Tyr(900) by phenylalanine (Y900F), were comparable with
      those of original RET-MEN2A, whereas those of the mutant Y905F were greatly
      decreased. Interestingly, those of a double mutant, Y900F/Y905F, were completely
      abolished. Both the kinase activity and transforming activity were impaired in
      the mutants Y806F and Y809F. These results provide convincing evidence for both
      previously suggested and new tyrosine autophosphorylation sites of RET as well as
      for novel functions of Tyr(806), Tyr(809), and Tyr(900) phosphorylation in both
      catalytic kinase activities and cell growth. The significance of the identified
      autophosphorylation sites in various protein-tyrosine kinases registered in a
      data base is discussed in this paper.

PMID- 14711814
TI  - Subcellular distribution of ADAR1 isoforms is synergistically determined by three
      nuclear discrimination signals and a regulatory motif.
AB  - ADAR1 is an RNA-specific adenosine deaminase that edits RNA sequences. We have
      demonstrated previously that different ADAR1 isoforms are induced during acute
      inflammation. Here we show that the mouse ADAR1 isoforms are differentially
      localized in cellular compartments and that their localization is controlled by
      several independent signals. Nuclear import of the full-length ADAR1 is
      predominantly regulated by a nuclear localization signal at the C terminus (NLS
      c), which consists of a bipartite basic amino acid motif plus the last 39
      residues of ADAR1. Deletion of the NLS-c causes the truncated ADAR1 protein to be
      retained in the cytoplasm. The addition of this sequence to pyruvate kinase
      causes the cytoplasmic protein to be localized within the nucleus. The
      localization of nuclear ADAR1 is determined by a dynamic balance between the
      nucleolar binding activity of the nucleolar localization signal (NoLS) in the
      middle of the protein and the exporting activity of the nuclear exporter signal
      (NES) near the N terminus. The NoLS consists of a typical monopartite cluster of
      basic residues followed by the third double-stranded RNA-binding domain. These
      signals act independently; however, NES function can be completely silenced by
      the NLS-c when a regulatory motif within the catalytic domain and the NoLS are
      deleted. Thus, the intracellular distribution of the various ADAR1 isoforms is
      determined by NLS-c, NES, NoLS, and a regulatory motif.

PMID- 14711815
TI  - Evidence supporting a role for calcium in apoptosis induction by the synthetic
      triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO).
AB  - The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)
      is a novel anticancer agent that induces apoptosis in tumor cells. The cytotoxic
      stress underpinning CDDO-induced apoptosis has not been established. This study
      compared and contrasted the effects of CDDO on COLO 16 human skin cancer cells
      and their respiration-deficient (rho(0)) clones to elucidate the stress signal
      responsible for initiating apoptosis. CDDO promoted apoptosis in COLO 16 cells in
      a dose- and time-dependent manner. The rho(0) clones appeared to be more
      sensitive to CDDO-induced apoptosis implying that the disruption of mitochondrial
      respiration was not directly associated with triggering cell death. After a 4-h
      exposure to CDDO, mitochondrial inner transmembrane potential-sensitive dyes
      revealed mitochondrial hyperpolarization in the COLO 16 cells and mitochondrial
      depolarization in the rho(0) clones. Electron microscopy illustrated that this
      exposure also promoted mitochondrial condensation, endoplasmic reticulum
      dilation, and chromatin condensation in the COLO 16 cells. Endoplasmic reticulum
      dilation and chromatin condensation were also observed in the rho(0) clones, but
      the mitochondria in these cells were markedly swollen implying that the
      disruption of intracellular Ca(2+) homeostasis was associated with cell death. A
      Ca(2+)-sensitive dye confirmed that CDDO increased cytoplasmic free Ca(2+) in the
      COLO 16 cells, their rho(0) clones, as well as in malignant breast and lung
      epithelial cells. A cell-permeant Ca(2+) chelator reduced the CDDO-induced
      increase in cytoplasmic free Ca(2+), and inhibited caspase activation, the
      development of apoptotic morphology, and DNA fragmentation in the COLO 16 cells,
      implying that Ca(2+) played a pivotal role in signaling the initiation of
      apoptosis.

PMID- 14711816
TI  - Genetic evidence for an interaction between a picornaviral cis-acting RNA
      replication element and 3CD protein.
AB  - Internally located, cis-acting RNA replication elements, termed cres, are
      essential for replication of the genomes of picornaviruses such as human
      rhinovirus 14 (HRV-14) and poliovirus because they template uridylylation of the
      protein primer, VPg, by the polymerase 3D(pol). These cres form stem-loop
      structures sharing a common loop motif, and the HRV-14 cre can substitute
      functionally for the poliovirus cre in both uridylylation in vitro and RNA
      replication in vivo. We show, however, that the poliovirus cre is unable to
      support HRV-14 RNA replication. This lack of complementation maps to the stem of
      the poliovirus cre and was reversed by single nucleotide substitutions in the
      stem as well as the base of the loop. Replication-competent, revertant viruses
      rescued from dicistronic HRV-14 RNAs containing the poliovirus cre, or a chimeric
      cre containing the poliovirus stem, contained adaptive amino acid substitutions.
      These mapped to the surface of both the polymerase 3D(pol), at the tip of the
      "thumb" domain, and the protease 3C(pro), on the side opposing the active site
      and near the end of an extended strand segment implicated previously in RNA
      binding. These mutations substantially enhanced replication competence when
      introduced into HRV-14 RNAs containing the poliovirus cre, and they were additive
      in their effects. The data support a model in which 3CD or its derivatives
      3C(pro) and 3D(pol) interact directly with the stem of the cre during
      uridylylation of VPg.

PMID- 14711817
TI  - NF-kappaB participates in the corticotropin-releasing, hormone-induced regulation
      of the pituitary proopiomelanocortin gene.
AB  - Corticotropin-releasing hormone is a main regulator of mammalian stress response
      by stimulating pituitary proopiomelanocortin (POMC) gene expression, and thus
      adrenocorticotropic hormone (ACTH) secretion, which then causes glucocorticoid
      release from the adrenal. In a recent study in the pituitary corticotroph cell
      line AtT20, oxidative stress stimulated the activity of nuclear transcription
      factor B (NF-kappaB), whereas corticotropin-releasing hormone (CRH) inhibited
      both the constitutive and the oxidative stress-induced NF-kappaB DNA-binding
      activity. To further investigate the role of NF-kappaB on the CRH-induced
      pituitary POMC gene activation, AtT20 cells were transiently transfected with a
      POMC-luciferase construct mutated at an NF-kappaB binding site. After treatment
      with CRH, intracellular POMC-luciferase activity was significantly higher from
      the stimulation observed with transfection of the parental POMC-luciferase
      construct. In agreement with a previous report, CRH inhibited the constitutive NF
      kappaB DNA-binding activity in AtT20 cells, as shown by electrophoretic mobility
      shift assay, as soon as within 15 min of treatment. These effects of CRH were
      blocked by the CRH-R1 antagonist CP154,256. Our findings provide evidence that
      the regulation of corticotroph NF-kappaB activity by CRH is related to the
      activation of the pituitary POMC gene and, thus, may play an important role in
      stress response.

PMID- 14711818
TI  - Translin-associated factor X is post-transcriptionally regulated by its partner
      protein TB-RBP, and both are essential for normal cell proliferation.
AB  - To determine the functions of the DNA/RNA-binding protein TB-RBP in somatic
      cells, we examined cultured primary mouse embryonic fibroblasts (MEFs) derived
      from TB-RBP-deficient mice. The TB-RBP-deficient MEFs exhibit a reduced growth
      rate compared with MEFs from littermates. Reintroduction of TB-RBP remedies this
      defect. A partner protein of TB-RBP, Translin-associated factor X (TRAX), was
      absent in TB-RBP-deficient MEFs, despite normal TRAX mRNA levels. TRAX is
      dependent upon the presence of TB-RBP and is removed from null MEFs following
      ubiquitination. Re-introduction of TB-RBP, but not TB-RBP lacking an
      oligomerization domain, into null MEFs stabilized TRAX protein without changing
      TRAX mRNA levels. The coordinated expression of TB-RBP and TRAX is also seen in
      synchronized cells, where the amount of TRAX protein but not TRAX RNA closely
      parallels TB-RBP levels throughout the cell cycle. In transgenic mice
      overexpressing TRAX in testis, total TB-RBP and TRAX levels are constant with
      reductions of endogenous TRAX compensating for exogenous TRAX. Using RNA
      interference, reductions of either TB-RBP or TRAX (without affecting TB-RBP) slow
      cell growth rates. We conclude that TRAX is post-transcriptionally stabilized by
      TB-RBP and both proteins are needed for normal cell proliferation.

PMID- 14711819
TI  - Involvement of insulin/phosphoinositide 3-kinase/Akt signal pathway in 17 beta
      estradiol-mediated neuroprotection.
AB  - In the present study, we tested the hypothesis that 17beta-estradiol (betaE2) is
      a neuroprotectant in the retina, using two experimental approaches: 1) hydrogen
      peroxide (H(2)O(2))-induced retinal neuron degeneration in vitro, and 2) light
      induced photoreceptor degeneration in vivo. We demonstrated that both betaE2 and
      17alpha-estradiol (alphaE2) significantly protected against H(2)O(2)-induced
      retinal neuron degeneration; however, progesterone had no effect. betaE2
      transiently increased the phosphoinositide 3-kinase (PI3K) activity, when
      phosphoinositide 4,5-bisphosphate and [(32)gammaATP] were used as substrate.
      Phospho-Akt levels were also transiently increased by betaE2 treatment. Addition
      of the estrogen receptor antagonist tamoxifen did not reverse the protective
      effect of betaE2, whereas the PI3K inhibitor LY294002 inhibited the protective
      effect of betaE2, suggesting that betaE2 mediates its effect through some PI3K
      dependent pathway, independent of the estrogen receptor. Pull-down experiments
      with glutathione S-transferase fused to the N-Src homology 2 domain of p85, the
      regulatory subunit of PI3K, indicated that betaE2 and alphaE2, but not
      progesterone, identified phosphorylated insulin receptor beta-subunit (IRbeta) as
      a binding partner. Pretreatment with insulin receptor inhibitor, HNMPA, inhibited
      IRbeta activation of PI3K. Systemic administration of betaE2 significantly
      protected the structure and function of rat retinas against light-induced
      photoreceptor cell degeneration and inhibited photoreceptor apoptosis. In
      addition, systemic administration of betaE2 activated retinal IRbeta, but not the
      insulin-like growth factor receptor-1, and produced a transient increase in PI3K
      activity and phosphorylation of Akt in rat retinas. The results show that
      estrogen has retinal neuroprotective properties in vivo and in vitro and suggest
      that the insulin receptor/PI3K/Akt signaling pathway is involved in estrogen
      mediated retinal neuroprotection.

PMID- 14711820
TI  - Identification and characterization of a phorbol ester-responsive element in the
      murine 8S-lipoxygenase gene.
AB  - Murine 8S-lipoxygenase (8S-LOX) is a 12-O-tetradecanoylphorbol-13-acetate (TPA)
      inducible lipoxygenase. That is, it is not detected in normal mouse skin,
      however, a significant increase in expression is detected in the skin of TPA
      promotion-sensitive strains of mice after TPA treatment. In this study, we found
      TPA-induced 8S-LOX mRNA expression is a result of increased transcription in SSIN
      primary keratinocytes and further investigated transcriptional regulation of 8S
      LOX expression by cloning its promoter. The cloned 8S-LOX promoter (
      approximately 2 kb) in which a transcription initiation site was mapped at -27
      from the ATG has neither a TATA box nor a CCAAT box. However, the promoter was
      highly responsive to TPA in TPA promotion-sensitive SSIN but not in TPA promotion
      resistant C57BL/6J primary keratinocytes. We then identified a Sp1 binding site
      located -77 to -68 from the ATG that is a TPA-responsive element (TRE) of the
      promoter and that Sp1, Sp2, and Sp3 proteins bind to the TRE. We also found that
      the binding of these proteins to the TRE was significantly increased by TPA
      treatment and inhibition of the binding by mithramycin A decreased TPA-induced
      promoter activity as well as 8S-LOX mRNA expression. These data suggest that
      increased binding of Sp1, Sp2, and Sp3 to the TRE of the 8S-LOX promoter is a
      mechanism by which TPA induces 8S-LOX expression in keratinocytes.

PMID- 14711821
TI  - Regulation of angiotensin II type 1A receptor intracellular retention,
      degradation, and recycling by Rab5, Rab7, and Rab11 GTPases.
AB  - Previous studies have demonstrated that the interaction of the angiotensin II
      type 1A receptor (AT(1A)R) carboxyl-terminal tail with Rab5a may modulate Rab5a
      activity, leading to the homotypic fusion of endocytic vesicles. Therefore, we
      have investigated whether AT(1A)R/Rab5a interactions mediate the retention of
      AT(1A)R.beta-arrestin complexes in early endosomes and whether the overexpression
      of Rab7 and Rab11 GTPases influences AT(1A)R lysosomal degradation and plasma
      membrane recycling. We found that internalized AT(1A)R was retained in Rab5a
      positive early endosomes and was neither targeted to lysosomes nor recycled back
      to the cell surface, whereas a mutant defective in Rab5a binding, AT(1A)R-(1
      349), was targeted to lysosomes for degradation. However, the loss of Rab5a
      binding to the AT(1A)R carboxyl-terminal tail did not promote AT(1A)R recycling.
      Rather, it was the stable binding of beta-arrestin to the AT(1A)R that prevented,
      at least in part, AT(1A)R recycling. The overexpression of wild-type Rab7 and
      Rab7-Q67L resulted in both increased AT(1A)R degradation and AT(1A)R targeting to
      lysosomes. The Rab7 expression-dependent transition of "putative" AT(1A)R.beta
      arrestin complexes to late endosomes was blocked by the expression of dominant
      negative Rab5a-S34N. Rab11 overexpression established AT(1A)R recycling and
      promoted the redistribution of AT(1A)R.beta-arrestin complexes from early to
      recycling endosomes. Taken together, our data suggest that Rab5, Rab7, and Rab11
      work in concert with one another to regulate the intracellular trafficking
      patterns of the AT(1A)R.

PMID- 14711822
TI  - Probing the ArcA-P modulon of Escherichia coli by whole genome transcriptional
      analysis and sequence recognition profiling.
AB  - The ArcB/ArcA two-component signal transduction system of Escherichia coli
      regulates gene expression in response to the redox conditions of growth. Over the
      years, genetic screens have lead to the identification of about 30 ArcA-P
      controlled operons that are involved in redox metabolism. However, the discovery
      of 3 targets that are not implicated in respiratory metabolism (the tra operon
      for plasmid conjugation, psi site for Xer-based recombination, and oriC site for
      chromosome replication) suggests that the Arc modulon may comprise additional
      operons that are involved in a myriad of functions. To identify these operons, we
      derived the ArcA-P-dependent transcription profile of E. coli using
      oligonucleotide-based microarray analysis. The findings indicated that 9% of all
      open reading frames in E. coli are affected either directly or indirectly by ArcA
      P. To identify which operons are under the direct control of ArcA-P, we developed
      the ArcA-P recognition weight matrix from footprinting data and used it to scan
      the genome, yielding an ArcA-P sequence affinity map. By overlaying both methods,
      we identified 55 new Arc-regulated operons that are implicated in energy
      metabolism, transport, survival, catabolism, and transcriptional regulation. The
      data also suggest that the Arc response pathway, which translates into a net
      global downscaling of gene expression, overlaps partly with the FNR regulatory
      network. A conservative but reasonable assessment is that the Arc pathway
      recruits 100-150 operons to mediate a role in cellular adaptation that is more
      extensive than hitherto anticipated.

PMID- 14711823
TI  - Rat long chain acyl-CoA synthetase 5, but not 1, 2, 3, or 4, complements
      Escherichia coli fadD.
AB  - Long chain fatty acids are converted to acyl-CoAs by acyl-CoA synthetase (fatty
      acid CoA ligase: AMP forming, E.C. 6.2.1.3; ACS). Escherichia coli has a single
      ACS, FadD, that is essential for growth when fatty acids are the sole carbon and
      energy source. Rodents have five ACS isoforms that differ in substrate
      specificity, tissue expression, and subcellular localization and are believed to
      channel fatty acids toward distinct metabolic pathways. We expressed rat ACS
      isoforms 1-5 in an E. coli strain that lacked FadD. All rat ACS isoforms were
      expressed in E. coli fadD or fadDfadR and had ACS specific activities that were
      1.6-20-fold higher than the wild type control strain expressing FadD. In the fadD
      background, the rat ACS isoforms 1, 2, 3, 4 and 5 oxidized [(14)C]oleate at 5 to
      25% of the wild type levels, but only ACS5 restored growth on oleate as the sole
      carbon source. To ensure that enzymes of beta-oxidation were not limiting, assays
      of ACS activity, beta-oxidation, fatty acid transport, and phospholipid synthesis
      were also examined in a fadD fadR strain, thereby eliminating FadR repression of
      the transporter FadL and the enzymes of beta-oxidation. In this strain, fatty
      acid transport levels were low but detectable for ACS1, 2, 3, and 4 and were
      nearly 50% of wild type levels for ACS5. Despite increases in beta-oxidation,
      only ACS5 transformants were able to grow on oleate. These studies show that
      although ACS isoforms 1-4 variably supported moderate transport activity, beta
      oxidation, and phospholipid synthesis and although their in vitro specific
      activities were greater than that of chromosomally encoded FadD, they were unable
      to substitute functionally for FadD regarding growth. Thus, membrane composition
      and protein-protein interactions may be critical in reconstituting bacterial ACS
      function.

PMID- 14711824
TI  - Reciprocal regulation of angiotensin receptor-activated extracellular signal
      regulated kinases by beta-arrestins 1 and 2.
AB  - beta-Arrestin2 not only plays essential roles in seven membrane-spanning receptor
      desensitization and internalization but also functions as a signal transducer in
      mitogen-activated protein kinase cascades. Here we show that the angiotensin II
      type 1A receptor-mediated activation of extracellular signal-regulated kinases 1
      and 2 (ERK1/2) in HEK-293 cells is increased when the cellular level of beta
      arrestin1 is down-regulated by RNA interference but is decreased or eliminated
      when the cellular level of beta-arrestin2 is diminished. Such reciprocal effects
      of down-regulated levels of beta-arrestins 1 and 2 are primarily due to
      differences in the ability of the two forms of beta-arrestins to directly mediate
      ERK activation. These results are the first to demonstrate reciprocal activity of
      beta-arrestin isoforms on a signaling pathway and suggest that physiological
      levels of beta-arrestin1 may act as "dominant-negative" inhibitors of beta
      arrestin2-mediated ERK activation.

PMID- 14711825
TI  - Identification and characterization of EhCaBP2. A second member of the calcium
      binding protein family of the protozoan parasite Entamoeba histolytica.
AB  - Entamoeba histolytica, an early branching eukaryote, is the etiologic agent of
      amebiasis. Calcium plays a pivotal role in the pathogenesis of amebiasis by
      modulating the cytopathic properties of the parasite. However, the mechanistic
      role of Ca(2+) and calcium-binding proteins in the pathogenesis of E. histolytica
      remains poorly understood. We had previously characterized a novel calcium
      binding protein (EhCaBP1) from E. histolytica. Here, we report the identification
      and partial characterization of an isoform of this protein, EhCaBP2. Both EhCaBPs
      have four canonical EF-hand Ca(2+) binding domains. The two isoforms are encoded
      by genes of the same size (402 bp). Comparison between the two genes showed an
      overall identity of 79% at the nucleotide sequence level. This identity dropped
      to 40% in the 75-nucleotide central linker region between the second and third
      Ca(2+) binding domains. Both of these genes are single copy, as revealed by
      Southern hybridization. Analysis of the available E. histolytica genome sequence
      data suggested that the two genes are non-allelic. Homology-based structural
      modeling showed that the major differences between the two EhCaBPs lie in the
      central linker region, normally involved in binding target molecules. A number of
      studies indicated that EhCaBP1 and EhCaBP2 are functionally different. They bind
      different sets of E. histolytica proteins in a Ca(2+)-dependent manner.
      Activation of endogenous kinase was also found to be unique for the two proteins
      and the Ca(2+) concentration required for their optimal functionality was also
      different. In addition, a 12-mer peptide was identified from a random peptide
      library that could differentially bind the two proteins. Our data suggest that
      EhCaBP2 is a new member of a class of E. histolytica calcium-binding proteins
      involved in a novel calcium signal transduction pathway.

PMID- 14711826
TI  - Blood lipid mediator sphingosine 1-phosphate potently stimulates platelet-derived
      growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent
      induction of Kruppel-like factor 5.
AB  - Platelet-derived growth factors (PDGFs), potent mitogens and chemoattractants for
      mesenchymal cell types, play essential roles in development of several organs
      including blood vessels, kidney, and lung, and are also implicated in the
      pathogenesis of atherosclerosis and malignancies. Blood lipid mediator
      sphingosine 1-phosphate (S1P) regulates migration, proliferation, and apoptosis
      in a variety of cell types through multiple G protein-coupled receptors of the
      Edg family, and is necessary for vascular formation at the developmental stage.
      We found in the present study that S1P induced severalfold increases in the mRNA
      and protein levels of PDGF-A and -B chains in vascular smooth muscle cells and
      neointimal cells. S1P stimulation of PDGF mRNA and protein expression was
      abolished by the small interfering RNA duplexes targeting S1P(1)/Edg1 receptor
      subtype. S1P stimulated the small GTPase Ras in a G(i)-dependent manner, and
      activated ERK and p38 MAPK in G(i)- and Ras-dependent manners. Pertussis toxin
      pretreatment, adenovirus-mediated Asn(17)Ras expression, the MEK inhibitor
      PD98059, or the p38 MAPK inhibitor SB203580 markedly suppressed PDGF mRNA and
      protein up-regulation, indicating the involvement of G(i)-Ras-ERK/p38 MAPK in S1P
      stimulation of PDGF expression. S1P stimulated expression of the transcription
      factor KLF5 in manners dependent on G(i), Ras, and ERK/p38 MAPK. Down-regulation
      of KLF5 by small interfering RNA duplexes abolished S1P-induced PDGF-A and -B
      chain expression. On the other hand, overexpression of KLF5 stimulated basal and
      S1P-induced PDGF expression. Either S1P stimulation or KLF5 overexpression
      increased the PDGF-B promoter activity in a cis-element-dependent manner. These
      results reveal the S1P(1)-triggered, G(i)-Ras-ERK/p38 MAPK-KLF5-dependent,
      stimulatory regulation of PDGF gene transcription in vascular smooth muscle
      cells.

PMID- 14711827
TI  - Proteasomal inhibition by alpha-synuclein filaments and oligomers.
AB  - A unifying feature of many neurodegenerative disorders is the accumulation of
      polyubiquitinated protein inclusions in dystrophic neurons, e.g. containing alpha
      synuclein, which is suggestive of an insufficient proteasomal activity. We
      demonstrate that alpha-synuclein and 20 S proteasome components co-localize in
      Lewy bodies and show that subunits from 20 S proteasome particles, in contrast to
      subunits of the 19 S regulatory complex, bind efficiently to aggregated
      filamentous but not monomeric alpha-synuclein. Proteasome binding to insoluble
      alpha-synuclein filaments and soluble alpha-synuclein oligomers results in marked
      inhibition of its chymotrypsin-like hydrolytic activity through a non-competitive
      mechanism that is mimicked by model amyloid-Abeta peptide aggregates. Endogenous
      ligands of aggregated alpha-synuclein like heat shock protein 70 and
      glyceraldehyde-6-phosphate dehydrogenase bind filaments and inhibit their anti
      proteasomal activity. The inhibitory effect of amyloid aggregates may thus be
      amenable to modulation by endogenous chaperones and possibly accessible for
      therapeutic intervention.

PMID- 14711828
TI  - ART-27, an androgen receptor coactivator regulated in prostate development and
      cancer.
AB  - Androgen receptor trapped clone-27 (ART-27) is a newly described transcriptional
      coactivator that binds to the N terminus of the androgen receptor (AR). Given the
      vital importance of AR signaling in prostate growth and differentiation, we
      investigated the role of ART-27 in these processes. Immunohistochemical studies
      indicate that ART-27 protein is expressed in differentiated epithelial cells of
      adult human prostate and breast tissue. In prostate, ART-27 is abundant in AR
      positive prostate luminal epithelial cells, in contrast to the stroma, where
      cells express AR but not ART-27. The use of a rat model of androgen
      depletion/reconstitution indicates that ART-27 expression is associated with the
      elaboration of differentiated prostate epithelial cells. Interestingly, regulated
      expression of ART-27 in the androgen-sensitive LNCaP prostate cancer cell line
      inhibits androgen-mediated cellular proliferation and enhances androgen-mediated
      transcription of the prostate-specific antigen (PSA) gene. Consistent with a
      growth suppressive function, we show that ART-27 expression levels are negligible
      in human prostate cancer. Importantly, examination of ART-27 protein expression
      in early fetal prostate development demonstrates that ART-27 is detected only
      when the developing prostate gland has proceeded from a solid mass of
      undifferentiated cells to a stage in which differentiated luminal epithelial
      cells are evident. Thus, ART-27 is an AR cofactor shown to be subject to both
      cell type and developmental regulation in humans. Overall, the results suggest
      that decreased levels of ART-27 protein in prostate cancer tissue may occur as a
      result of de-differentiation, and indicate that ART-27 is likely to regulate a
      subset of AR-responsive genes important to prostate growth suppression and
      differentiation.

PMID- 14711830
TI  - Hepatitis C virus core functions as a suppressor of cyclin-dependent kinase
      activating kinase and impairs cell cycle progression.
AB  - We investigated how the hepatitis C virus (HCV) core protein affects the cell
      cycle profile and cell cycle-related molecules by using the HCV core-expressing
      stable transfectant. Analysis of the cell cycle profile showed that HCV core
      impaired G(1) to S transition. The E2F-mediated transcription, phosphorylation of
      the retinoblastoma protein, and cyclin-dependent kinase (CDK) 4 and CDK2
      activities were suppressed in HCV core-expressing cells. The expression levels of
      G(1) phase-related CDKs/cyclins and various CDK inhibitors were not substantially
      affected by expression of HCV core. When influences of HCV core on CDK-activating
      kinase (CAK) were examined, the expression levels of the CAK components, CDK7,
      cyclin H, and MAT1, were not affected. However, formation of the ternary CAK
      complex, CAK activity, and the CDK2 level with activating phosphorylation were
      inhibited by expression of the HCV core. The direct effect of HCV core on CAK was
      further assessed in the cell-free system by adding the in vitro translated HCV
      core protein to the anti-CDK7 immunoprecipitate from the cell. The results showed
      that HCV core led to dissociation of MAT1 from the CAK complex and suppressed the
      CAK activity. Furthermore, the binding assay revealed that the HCV core was
      directed against CDK7. Their interaction occurred mainly in the nucleus by the
      immunostaining. In conclusion, the HCV core protein interacts with CAK and
      functions as an extrinsic suppressor of CAK. This may be the molecular basis of
      HCV core-mediated suppression of cell cycle progression. Our findings suggest a
      novel mechanism concerning HCV core-mediated alteration in the cell cycle
      machinery.

PMID- 14711829
TI  - Neuregulin signaling on glucose transport in muscle cells.
AB  - Neuregulin-1, a growth factor that potentiates myogenesis induces glucose
      transport through translocation of glucose transporters, in an additive manner to
      insulin, in muscle cells. In this study, we examined the signaling pathway
      required for a recombinant active neuregulin-1 isoform (rhHeregulin-beta(1), 177
      244, HRG) to stimulate glucose uptake in L6E9 myotubes. The stimulatory effect of
      HRG required binding to ErbB3 in L6E9 myotubes. PI3K activity is required for HRG
      action in both muscle cells and tissue. In L6E9 myotubes, HRG stimulated
      PKBalpha, PKBgamma, and PKCzeta activities. TPCK, an inhibitor of PDK1, abolished
      both HRG- and insulin-induced glucose transport. To assess whether PKB was
      necessary for the effects of HRG on glucose uptake, cells were infected with
      adenoviruses encoding dominant negative mutants of PKBalpha. Dominant negative
      PKB reduced PKB activity and insulin-stimulated glucose transport but not HRG
      induced glucose transport. In contrast, transduction of L6E9 myotubes with
      adenoviruses encoding a dominant negative kinase-inactive PKCzeta abolished both
      HRG- and insulin-stimulated glucose uptake. In soleus muscle, HRG induced
      PKCzeta, but not PKB phosphorylation. HRG also stimulated the activity of p70S6K,
      p38MAPK, and p42/p44MAPK and inhibition of p42/p44MAPK partially repressed HRG
      action on glucose uptake. HRG did not affect AMPKalpha(1) or AMPKalpha(2)
      activities. In all, HRG stimulated glucose transport in muscle cells by
      activation of a pathway that requires PI3K, PDK1, and PKCzeta, but not PKB, and
      that shows cross-talk with the MAPK pathway. The PI3K, PDK1, and PKCzeta pathway
      can be considered as an alternative mechanism, independent of insulin, to induce
      glucose uptake.

PMID- 14711831
TI  - Protein kinase C-zeta and protein kinase B regulate distinct steps of insulin
      endocytosis and intracellular sorting.
AB  - We have investigated the molecular mechanisms regulating insulin internalization
      and intracellular sorting. Insulin internalization was decreased by 50% upon
      incubation of the cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors
      wortmannin and LY294002. PI3K inhibition also reduced insulin degradation and
      intact insulin release by 50 and 75%, respectively. Insulin internalization was
      reduced by antisense inhibition of protein kinase C-zeta (PKCzeta) expression and
      by overexpression of a dominant negative PKCzeta mutant (DN-PKCzeta). Conversely,
      overexpression of PKCzeta increased insulin internalization as a function of the
      PKCzeta levels achieved in the cells. Expression of wild-type protein kinase B
      (PKB)-alpha or of a constitutively active form (myr-PKB) did not significantly
      alter insulin internalization and degradation but produced a 100% increase of
      intact insulin release. Inhibition of PKB by a dominant negative mutant (DN-PKB)
      or by the pharmacological inhibitor ML-9 reduced intact insulin release by 75%
      with no effect on internalization and degradation. In addition, overexpression of
      Rab5 completely rescued the effect of PKCzeta inhibition on insulin
      internalization but not that of PKB inhibition on intact insulin recycling.
      Indeed, PKCzeta bound to and activated Rab5. Thus, PI3K controls different steps
      within the insulin endocytic itinerary. PKCzeta appears to mediate the PI3K
      effect on insulin internalization in a Rab5-dependent manner, whereas PKB directs
      intracellular sorting toward intact insulin release.

PMID- 14711832
TI  - Tissue distribution of AU-rich mRNA-binding proteins involved in regulation of
      mRNA decay.
AB  - Short lived cytokine and proto-oncogene mRNAs are destabilized by an A+U-rich
      element (ARE) in the 3'-untranslated region. Several regulatory proteins bind to
      AREs in cytokine and proto-oncogene mRNAs, participate in inhibiting or promoting
      their rapid degradation of ARE mRNAs, and influence cytokine expression and
      cellular transformation in experimental models. The tissue distribution and
      cellular localization of the different AU-rich binding proteins (AUBPs), however,
      have not been uniformly characterized in the mouse, a model for ARE mRNA decay.
      We therefore carried out immunoblot and immunohistochemical analyses of the
      different AUBPs using the same mouse tissues. We show that HuR protein, a major
      AUBP that stabilizes the ARE mRNAs, is most strongly expressed in the thymus,
      spleen (predominantly in lymphocytic cells), intestine, and testes. AUF1 protein,
      a negative regulator of ARE mRNA stability, displayed strong expression in thymus
      and spleen cells within lymphocytic cells, moderate expression in the epithelial
      linings of lungs, gonadal tissues, and nuclei of most neurons in the brain, and
      little expression in the other tissues. Tristetraprolin, a negative regulator of
      ARE mRNA stability, displayed a largely non-overlapping tissue distribution with
      AUF1 and was predominantly expressed in the liver and testis. KH-type splicing
      regulatory protein, a presumptive negative regulator of ARE mRNA stability, was
      distributed widely in murine organs. These results indicate that HuR and AUF1,
      which functionally oppose each other, have generally similar distributions,
      suggesting that the balance between HuR and AUF1 is likely important in control
      of short lived mRNA degradation, lymphocyte development, and/or cytokine
      production, and possibly in certain aspects of neurological function.

PMID- 14711834
TI  - Structural determinants of conformationally selective, prion-binding aptamers.
AB  - We have recently described the isolation of 2'-fluoropyrimidine-substituted RNA
      aptamers that bind selectively to disease-associated beta-sheet-rich forms of the
      prion protein, PrP, from a number of mammalian species. These aptamers inhibit
      the accumulation of protease-resistant forms of PrP in a prion-seeded, in vitro
      conversion assay. Here we identify the minimal portions of two of these aptamers
      that retain binding specificity. We determine their secondary structures by a
      combination of modeling and solution probing. Finally, we identify an internal
      site for biotinylation of a minimized, synthetic aptamer and use the resultant
      reagent in the detection of abnormal forms of PrP in vitro.

PMID- 14711833
TI  - Heat-shock treatment-mediated increase in transduction by recombinant adeno
      associated virus 2 vectors is independent of the cellular heat-shock protein 90.
AB  - Recombinant adeno-associated virus 2 (AAV) vectors transduction efficiency varies
      greatly in different cell types. We have described that a cellular protein,
      FKBP52, in its phosphorylated form interacts with the D-sequence in the viral
      inverted terminal repeat, inhibits viral second strand DNA synthesis, and limits
      transgene expression. Here we investigated the role of cellular heat-shock
      protein 90 (HSP90) in AAV transduction because FKBP52 forms a complex with HSP90,
      and because heat-shock treatment augments AAV transduction efficiency. Heat-shock
      treatment of HeLa cells resulted in tyrosine dephosphorylation of FKBP52, led to
      stabilization of the FKBP52-HSP90 complex, and resulted in approximately 6-fold
      increase in AAV transduction. However, when HeLa cells were pre-treated with
      tyrphostin 23, a specific inhibitor of cellular epidermal growth factor receptor
      tyrosine kinase, which phosphorylates FKBP52 at tyrosine residues, heat-shock
      treatment resulted in a further 18-fold increase in AAV transduction. HSP90 was
      shown to be a part of the FKBP52-AAV D-sequence complex, but HSP90 by itself did
      not bind to the D-sequence. Geldanamycin treatment, which disrupts the HSP90
      FKBP52 complex, resulted in >22-fold increase in AAV transduction in heat-shock
      treated cells compared with heat shock alone. Deliberate overexpression of the
      human HSP90 gene resulted in a significant decrease in AAV-mediated transduction
      in tyrphostin 23-treated cells, whereas down-modulation of HSP90 levels led to a
      decrease in HSP90-FKBP52-AAV D-sequence complex formation, resulting in a
      significant increase in AAV transduction following pre-treatment with tyrphostin
      23. These studies suggest that the observed increase in AAV transduction
      efficiency following heat-shock treatment is unlikely to be mediated by HSP90
      alone and that increased levels of HSP90, in the absence of heat shock,
      facilitate binding of FKBP52 to the AAV D-sequence, thereby leading to inhibition
      of AAV-mediated transgene expression. These studies have implications in the
      optimal use of recombinant AAV vectors in human gene therapy.

PMID- 14711835
TI  - Identification of a p65 peptide that selectively inhibits NF-kappa B activation
      induced by various inflammatory stimuli and its role in down-regulation of NF
      kappaB-mediated gene expression and up-regulation of apoptosis.
AB  - Because of the critical role of the nuclear transcription factor NF-kappaB in
      inflammation, viral replication, carcinogenesis, antiapoptosis, invasion, and
      metastasis, specific inhibitors of this nuclear factor are being sought and
      tested as treatments. NF-kappaB activation is known to require p65
      phosphorylation at serine residues 276, 529, and 536 before it undergoes nuclear
      translocation. Small protein domains, termed protein transduction domains (PTDs),
      which are able to penetrate cell membranes can be used to transport other
      proteins across the cell membrane. We have identified two peptides from the p65
      subunit of NF-kappaB (P1 and P6 were from amino acid residues 271-282 and 525
      537, respectively) that, when linked with a PTD derived from the third helix
      sequence of antennapedia, inhibited tumor necrosis factor (TNF)-induced NF-kappaB
      activation in vivo. Linkage to the PTD was not, however, required to suppress the
      binding of the p50-p65-heterodimer to the DNA in vitro. PTD-p65-P1 had no effect
      on TNF-induced AP-1 activation. PTD-p65-P1 suppressed NF-kappaB activation
      induced by lipopolysaccharide, interleukin-1, okadaic acid, phorbol 12-myristate
      13-acetate, H(2)O(2), and cigarette smoke condensate as well as that induced by
      TNF. PTD-p65-P1 had no effect on TNF-induced inhibitory subunit of NF
      kappaB(IkappaBalpha) phosphorylation, IkappaBalpha degradation, or IkappaBalpha
      kinase activation, but it blocked TNF-induced p65 phosphorylation and nuclear
      translocation. NF-kappaB-regulated reporter gene expression induced by TNF, TNF
      receptor 1, TNF receptor-associated death domain, TNF receptor-associated factor
      2, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65 was also suppressed by
      these peptides. Suppression of NF-kappaB by PTD-p65-P1 enhanced the apoptosis
      induced by TNF and chemotherapeutic agents. Overall, our results demonstrate the
      identification of a p65 peptide that can selectively inhibit NF-kappaB activation
      induced by various inflammatory stimuli, down-regulate NF-kappaB-mediated gene
      expression, and up-regulate apoptosis.

PMID- 14711836
TI  - Characterization of a novel C-type lectin-like gene, LSECtin: demonstration of
      carbohydrate binding and expression in sinusoidal endothelial cells of liver and
      lymph node.
AB  - A new C-type lectin-like gene encodes 293 amino acids and maps to chromosome
      19p13.3 adjacent to the previously described C-type lectin genes, CD23, dendritic
      cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN),
      and DC-SIGN-related protein (DC-SIGNR). The four genes form a tight cluster in an
      insert size of 105 kb and have analogous genomic structures. The new C-type
      lectin-like molecule, designated liver and lymph node sinusoidal endothelial cell
      C-type lectin (LSECtin), is a type II integral membrane protein of approximately
      40 kDa in size with a single C-type lectin-like domain at the COOH terminus,
      closest in homology to DC-SIGNR, DC-SIGN, and CD23. LSECtin mRNA was only
      expressed in liver and lymph node among 15 human tissues tested, intriguingly
      neither expressed on hematopoietic cell lines nor on monocyte-derived dendritic
      cells (DCs). Moreover, LSECtin is expressed predominantly by sinusoidal
      endothelial cells of human liver and lymph node and co-expressed with DC-SIGNR.
      LSECtin binds to mannose, GlcNAc, and fucose in a Ca(2+)-dependent manner but not
      to galactose. Our results indicate that LSECtin is a novel member of a family of
      proteins comprising CD23, DC-SIGN, and DC-SIGNR and might function in vivo as a
      lectin receptor.

PMID- 14711837
TI  - Established and potential strategies against papillomavirus infections.
AB  - Anogenital cancers, in particular cancer of the cervix, and common, genital and
      laryngeal warts are primarily caused by infection with human papillomaviruses.
      Traditionally, the primary goal of treatment is to remove the neoplasia by
      various surgical approaches; however, all of these have high rates of recurrence.
      Only a few non-surgical treatments have found their way into clinical practice,
      and none of them is generally recommended because of side effects, limited
      efficacy and recurrences. This article summarizes the research on pharmaceutical
      and immunological approaches that may find a place in clinical practice to
      complement or replace surgical treatments.

PMID- 14711839
TI  - Antimicrobial usage and resistance trend relationships from the MYSTIC Programme
      in North America (1999-2001).
AB  - BACKGROUND: The MYSTIC Programme is a global, longitudinal antimicrobial
      surveillance network of hospitals that frequently utilize carbapenems. One aspect
      of the programme is the ability to capture antimicrobial consumption data from
      participating institutions. The current report evaluates these relationships for
      Enterobacteriaceae and Pseudomonas aeruginosa over the initial 3 year period of
      the programme in the USA. METHODS: Between 10 and 15 medical centres participated
      during 1999-2001, each submitting up to 200 isolates/year (7003 strains overall).
      Evaluations of the relationship between drug usage and antimicrobial resistance
      in P. aeruginosa and Enterobacteriaceae for the carbapenems (imipenem and
      meropenem), cefepime, ceftazidime, ciprofloxacin, gentamicin and piperacillin
      tazobactam were determined. Data were analysed based on: (1) aggregate usage
      results; (2) medical centre-specific usage compared with resistance rates; and
      (3) medical centre-specific usage results compared with yearly changes in
      resistance rates (DeltaR). The parameter of drug usage was the defined daily dose
      (DDD)/100 patient days calculated from total grams administered, using WHO
      definitions. RESULTS: Resistance (1999-2001) among Enterobacteriaceae did not
      change significantly for beta-lactams, but tended to increase slightly for
      gentamicin (+1.1%) and ciprofloxacin (+3.1%). P. aeruginosa resistance rates
      (1999-2001) for gentamicin (+9.0%) and ciprofloxacin (+10.2%) increased, in
      contrast to a significantly decreased resistance rate for meropenem (-7.7%).
      Formulary-use changes were noted: increased meropenem and ciprofloxacin use and
      decreased consumption for imipenem, aminoglycosides, ceftazidime and cefepime.
      Aggregate ciprofloxacin DDD/100 days rates were directly related (+3.3 DDD) to
      Enterobacteriaceae and P. aeruginosa resistance changes, whereas among P.
      aeruginosa, usage and resistance were inversely correlated for gentamicin (-3.8
      DDD; +9.0% resistant). Medical centre-specific antimicrobial usage calculations
      did not demonstrate a correlation to rates of resistance (r = -0.38 to 0.61) or
      yearly changes in resistance rates (r = -0.56 to 0.43). CONCLUSIONS: The
      availability of aggregate USA medical centre antimicrobial usage data enabled us
      to identify several important trends in the incidence of resistance among P.
      aeruginosa and Enterobacteriaceae: (1) increased use of ciprofloxacin associated
      with a higher resistance among Enterobacteriaceae; and (2) a correlation between
      ciprofloxacin categories of resistance and levels of resistance to other
      antimicrobial classes in P. aeruginosa. Medical centre-specific antimicrobial
      usage and resistance did not demonstrate direct statistical relationships, and
      require a continued search for other monitoring methods that can better identify
      antimicrobial/environmental factors that lead to resistance.

PMID- 14711838
TI  - Effect of a 5 day enrofloxacin treatment on Salmonella enterica serotype
      Typhimurium DT104 in the pig.
AB  - OBJECTIVES: There are concerns that the use of enrofloxacin in livestock
      production may contribute to the development of fluoroquinolone resistance in
      zoonotic bacteria. The objective of our study was to investigate the effect of a
      single 5 day enrofloxacin treatment on Salmonella enterica serotype Typhimurium
      DT104 in a pig model. RESULTS: Our results showed that a single treatment failed
      to eradicate S. Typhimurium DT104, which continued to be isolated up to 35 days
      after treatment. We also provide evidence that treatment positively selects for
      S. Typhimurium DT104 strains that are already nalidixic acid resistant (gyrA Asn
      87) or cyclohexane resistant, the latter being indicative of an up-regulated
      efflux pump. Emergence of fluoroquinolone resistance was not detected during
      treatment or post-treatment in any of the Salmonella strains monitored. However,
      the effect of enrofloxacin on the nalidixic acid-resistant and cyclohexane
      resistant S. Typhimurium DT104 outlasted the current withdrawal time of 10 days
      for Baytril (commercial veterinary formulation of enrofloxacin). CONCLUSIONS: In
      conclusion, our study has provided direct evidence that enrofloxacin-treated pigs
      could be entering abattoirs with higher numbers of quinolone-resistant zoonotic
      bacteria than untreated pigs, increasing the risk of these entering the food
      chain.

PMID- 14711841
TI  - Should euthanasia be legal? An international survey of neonatal intensive care
      units staff.

PMID- 14711840
TI  - Linezolid versus teicoplanin in the treatment of Gram-positive infections in the
      critically ill: a randomized, double-blind, multicentre study.
AB  - OBJECTIVES: Linezolid, the only commercially available oxazolidinone, is
      indicated for the treatment of Gram-positive infections, although little has been
      published specifically on its use in the critically ill. A randomized,
      prospective study was therefore performed to compare linezolid with the
      glycopeptide antibiotic, teicoplanin, for the treatment of suspected or proven
      Gram-positive infections in an intensive care population. METHODS: Using a double
      blind, double-dummy, prospective design, patients were randomized to (i)
      intravenous linezolid (600 mg/12 h) plus teicoplanin dummy [one dose/12 h for
      three doses then every 24 h intravenously (iv)] or (ii) teicoplanin (400 mg/12 h
      for three doses then 400 mg/24 h iv) plus linezolid dummy (one dose/12 h iv).
      Other antibiotics were used in combination with the trial agents in empirical
      treatment. Clinical and microbiological assessments were made daily in the first
      week, and at 8 and 21 days after treatment. RESULTS: One hundred patients
      received linezolid plus placebo-teicoplanin, whereas 102 received teicoplanin
      plus placebo-linezolid. Population baseline characteristics were similar in both
      groups. At end of treatment, clinical success [71 (78.9%) linezolid versus 67
      (72.8%) teicoplanin] and microbiological success [49 (70.0%) versus 45 (66.2%)]
      rates were similar, as were adverse effects, intensive care unit mortality, and
      success rates at short- and long-term follow-up. Linezolid was superior at
      initial clearance of methicillin-resistant Staphylococcus aureus (MRSA)
      colonization (end of treatment, 51.1% versus 18.6%, P = 0.002). Two MRSA isolates
      showed reduced susceptibility to teicoplanin. CONCLUSIONS: Linezolid has similar
      safety and efficacy to teicoplanin in treating Gram-positive infections in the
      critically ill. Short-term MRSA clearance achieved with linezolid suggests better
      skin and mucosal penetration.

PMID- 14711842
TI  - Disentangling PK-PD in neonates.

PMID- 14711843
TI  - Should euthanasia be legal? An international survey of neonatal intensive care
      units staff.

PMID- 14711844
TI  - Can polyclonal intravenous immunoglobulin limit cytokine mediated cerebral damage
      and chronic lung disease in preterm infants?
AB  - Recent evidence suggests that inflammatory cytokines may play an important role
      in cerebral and pulmonary injury, especially in preterm infants. Immunomodulatory
      agents may help to limit such injury by reducing inflammation. Immunoglobulin has
      multiple anti-inflammatory properties and can modulate the inflammatory cytokine
      response. New evidence is required to test the hypotheses that prophylaxis or
      treatment with intravenous immunoglobulin may limit such inflammatory damage.

PMID- 14711846
TI  - Project 27/28. An enquiry into the quality of care and its effect on the survival
      of babies born at 27-28 weeks.

PMID- 14711845
TI  - Isolated mild fetal ventriculomegaly.
AB  - Ventriculomegaly is an excess of fluid in the lateral ventricles within the
      developing cerebrum. It is usually diagnosed at a routine fetal anomaly scan at
      18-22 weeks gestation. Management of the condition and counselling of parents are
      difficult, as the cause, absolute risk, and degree of resulting handicap cannot
      be determined with confidence.

PMID- 14711847
TI  - Oral sucrose analgesia for preterm infant venepuncture.

PMID- 14711848
TI  - Should euthanasia be legal? An international survey of neonatal intensive care
      units staff.
AB  - OBJECTIVE: To present the views of a representative sample of neonatal doctors
      and nurses in 10 European countries on the moral acceptability of active
      euthanasia and its legal regulation. DESIGN: A total of 142 neonatal intensive
      care units were recruited by census (in the Netherlands, Sweden, Hungary, and the
      Baltic countries) or random sampling (in France, Germany, Italy, Spain, and the
      United Kingdom); 1391 doctors and 3410 nurses completed an anonymous
      questionnaire (response rates 89% and 86% respectively). MAIN OUTCOME MEASURE:
      The staff opinion that the law in their country should be changed to allow active
      euthanasia "more than now". RESULTS: Active euthanasia appeared to be both
      acceptable and practiced in the Netherlands, France, and to a lesser extent
      Lithuania, and less acceptable in Sweden, Hungary, Italy, and Spain. More then
      half (53%) of the doctors in the Netherlands, but only a quarter (24%) in France
      felt that the law should be changed to allow active euthanasia "more than now".
      For 40% of French doctors, end of life issues should not be regulated by law.
      Being male, regular involvement in research, less than six years professional
      experience, and having ever participated in a decision of active euthanasia were
      positively associated with an opinion favouring relaxation of legal constraints.
      Having had children, religiousness, and believing in the absolute value of human
      life showed a negative association. Nurses were slightly more likely to consider
      active euthanasia acceptable in selected circumstances, and to feel that the law
      should be changed to allow it more than now. CONCLUSIONS: Opinions of health
      professionals vary widely between countries, and, even where neonatal euthanasia
      is already practiced, do not uniformly support its legalisation.

PMID- 14711849
TI  - Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of
      gestational age.
AB  - AIM: To investigate the pharmacokinetics and pharmacodynamics of single dose
      propacetamol in preterm and term infants on the first day of life. METHODS:
      Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41
      weeks) infants received a single dose of propacetamol in the first 24 hours of
      life when they had minor, painful procedures or as additional treatment in
      infants receiving opioids. Blood samples were taken from an arterial line, and
      pain was evaluated by a multidimensional pain scale. Results were reported as
      mean (SD). Student's t and Wilcoxon tests were used to compare the groups.
      RESULTS: Thirty neonates were included, 10 of which were term infants. Serum half
      life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the
      term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm
      infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational
      age correlated with serum half life (r = -0.46). No effect of sex or
      administration of prenatal steroids was found on the pharmacokinetics of
      paracetamol. In neonates who only received propacetamol (n = 15), the level of
      analgesia seemed to be associated with the therapeutic (> 5 mg/l) level.
      CONCLUSIONS: A correlation was found between gestational age and the serum half
      life of propacetamol. The maturational trend of clearance and half life in
      preterm and term neonates is in line with data on the pharmacokinetics of
      propacetamol beyond the newborn period.

PMID- 14711850
TI  - Human fetal and maternal corticotrophin releasing hormone responses to acute
      stress.
AB  - OBJECTIVES: To study the effect of acute stress, caused by intrauterine needling
      at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin
      releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH
      concentration to determine the extent of their joint control. DESIGN: Venous
      blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing
      fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either
      the IHV or the placental cord insertion (PCI). SETTING: The Centre for Fetal
      Care, Queen Charlotte's and Chelsea Hospital, London, UK. PATIENTS: Pregnant
      women undergoing clinically indicated fetal blood sampling or intrauterine
      blood/platelet transfusion. RESULTS: Fetal plasma cortisol increased with
      intrahepatic vein transfusion (mean (SD) cortisol response Delta64.7 (54.5)
      nmol/l; p < 0.0001, n = 11), and fetal corticotrophin concentrations were higher
      after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma
      CRH increased after IHV transfusion. Fetal CRH levels did not rise with
      gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p < 0.0001). There
      was a modest correlation between paired maternal and fetal values (r = 0.36; n =
      36; p = 0.03). CONCLUSIONS: Acute fetal stress, caused by IHV needling of the
      fetal abdomen, resulted in hypothalamic-pituitary-adrenal axis activation, as
      shown by a rise in fetal cortisol and corticotrophin. However, it did not result
      in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH
      is not derived from the hypophyseal-portal circulation, but from another source,
      presumably the placenta.

PMID- 14711851
TI  - Outcomes of infants born to mothers receiving methadone for pain management in
      pregnancy.
AB  - OBJECTIVE: To assess the outcomes of infants born to mothers receiving methadone
      for the management of pain in pregnancy. DESIGN: A retrospective audit was
      conducted of neonatal outcomes in 19 cases in which methadone was used in the
      management of maternal pain (pain group). Twenty four cases in which methadone
      was used for maintenance of opiate addiction in pregnancy served as a comparison
      group (maintenance group). SETTING: Regional level 3 neonatal service. RESULTS:
      Infants in the pain group were exposed to significantly smaller methadone doses,
      for shorter periods, starting later in pregnancy. Only 11% of them required
      treatment for neonatal abstinence syndrome, whereas 58% of infants in the
      maintenance group required treatment. Other neonatal morbidity in the pain group
      was considerable, probably related to prematurity. Infants in the pain group had
      significantly higher z scores for birth weight and head circumference, but not
      length, than the infants in the maintenance group. CONCLUSIONS: Methadone used
      for the treatment of maternal pain resulted in a low incidence of neonatal
      abstinence syndrome. Infants were normally grown. However, there was significant
      morbidity related to slight prematurity, and delivery in this group should be
      delayed until term if possible.

PMID- 14711852
TI  - Non-expert use of the cerebral function monitor for neonatal seizure detection.
AB  - BACKGROUND: The cerebral function monitor (CFM) is widely used to detect neonatal
      seizures, but there are very few studies comparing it with simultaneous
      electroencephalography (EEG). OBJECTIVE: To determine the accuracy of non-expert
      use of the CFM and to assess interobserver agreement of CFM seizure detection.
      PATIENTS: Babies admitted to the neonatal intensive care unit at King's College
      Hospital who were at high risk of seizure and had video-EEG monitoring. METHODS:
      Video-EEG was used to detect seizures. Each baby had CFM recordings at speeds of
      6, 15, and 30 cm/h during the EEG. Four neonatologists, trained in CFM seizure
      recognition, independently rated one hour CFM samples at three speeds from each
      baby. Interobserver agreement was quantified using Cohen's kappa. RESULTS: CFM
      traces from 19 babies with EEG seizures and 21 babies without EEG seizures were
      analysed. Overall non-expert interpretation of the CFM performed poorly as a
      seizure detector compared with simultaneous EEG (sensitivities 38% at 6 cm/h; 54%
      at 15 cm/h; 55% at 30 cm/h). Although babies with seizures were more likely to be
      correctly classified at higher speeds (p = 0.02), babies without seizures were
      also more likely to be misclassified (p < 0.001). Agreement between observers was
      not good at any speed (kappa values from 0.01 to 0.39). The observers usually
      detected generalised seizures but often missed seizures that were focal, low
      amplitude, or lasted less than one minute. CONCLUSION: Approximately half of all
      neonatal seizures may be missed using CFM alone. Neonatal seizures need to be
      diagnosed, characterised, and quantified first using EEG. The CFM may then be
      useful for long term monitoring.

PMID- 14711854
TI  - Does radio-opaque contrast improve radiographic localisation of percutaneous
      central venous lines?
AB  - BACKGROUND: Percutaneous central venous lines (long lines) are commonly used in
      neonatal practice. The position of these lines is important, because incorrect
      placement may be associated with complications. AIMS: To determine whether the
      addition of radio-opaque contrast material improves the localisation of long line
      tips over plain radiography. METHODS: Radiographs taken to identify long line
      position were identified in two periods; 106 radiographs without contrast taken
      between October 1999 and August 2000, and 96 radiographs with contrast between
      September 2001 and July 2002. Two observers independently reviewed each
      radiograph to identify the position of the line tip. The formal radiology report
      was recorded as a third observer. RESULTS: The use of contrast increased the
      proportion of radiographs in which all observers reported they could see the long
      line tip (53 (55%) v 41 (39%)). It also increased the proportion where they
      agreed on anatomical position (57 (59%) v 39 (37%)) and there was a higher kappa
      coefficient for agreement (0.56 v 0.33). CONCLUSIONS: The use of contrast while
      taking radiographs for the localisation of long line position improves the
      likelihood that an observer can see a long line tip and reduces inter-observer
      variability. Even using contrast, precise localisation of a long line tip can be
      difficult.

PMID- 14711855
TI  - Long line positioning in neonates: does computed radiography improve visibility?
AB  - OBJECTIVES: To assess the use of soft copy reporting of computed radiography (CR)
      images in determining intravenous long line tip position in neonates and compare
      visibility rates with hard copy printed images. METHOD: A retrospective study of
      all long lines inserted on the neonatal unit over a period of one year was
      performed. Forty five lines were inserted in 30 neonates over this time.
      Assessment of the CR images was made by three independent observers by reviewing
      the films on the viewing console and as hard copy printed films. RESULTS:
      Accurate identification of the line tip could be made in 66.7% of cases (kappa =
      0.9) using hard copy images and 95.6% cases (kappa = 1.0) using soft copy
      reporting (significant difference: p = 0.002). The difference in percentage
      visibility using the two techniques was 28.9% (95% confidence interval 10.2% to
      36.7%). CONCLUSION: The use of soft copy review of CR image improves the
      visibility of the line tip position compared with hard copy films and reduces the
      need for repeat radiographs with/without intravenous contrast.

PMID- 14711856
TI  - Early physiological development of infants with intrauterine growth retardation.
AB  - OBJECTIVES: To assess the patterns of early postnatal physiological adaptation
      and maturation in intrauterine growth retarded (IUGR) infants by measuring
      changes in sleeping deep body temperature, heart rate, and concentrations of
      urinary cortisol. SETTING: At home. PATIENTS: Sixty five IUGR babies and 127
      controls matched for sex, social class, and levels of parental smoking. RESULTS:
      Night time sleeping deep body temperature, heart rate, and cortisol excretion
      fell with age, eventually establishing an adult type diurnal rhythm of
      physiological function. Minimum overnight temperature showed a linear decline
      with age (p < 0.001), but the IUGR infants and the controls had significant
      differences in intercept (p = 0.007) and slope (p = 0.02). The estimated rate of
      decline per week was 0.020 degrees C for IUGR infants and 0.031 degrees C for
      controls. Maximum temperature did not show similar changes. IUGR infants had a
      mean (SE) age adjusted minimum overnight heart rate that was 4.2 (1.5) beats/min
      (p = 0.005) higher than controls. Overnight cortisol/creatinine ratios declined
      with age at a rate of 4.1% per week (log ratio -0.421 (0.0165), p = 0.01), but
      the ratio for IUGR infants was on average 42% higher (log ratio 0.35 (0.11), p =
      0.002) than for controls of the same age. Morning cortisol concentrations did not
      show a similar pattern. CONCLUSIONS: Postnatal physiological adaptation and
      maturation of IUGR infants is slower than normal and therefore they remain in a
      physiologically immature state for longer. The higher heart rates and greater
      cortisol excretion in such infants may be precursors to hypertension and
      cardiovascular disease seen in adults.

PMID- 14711857
TI  - Associations between perinatal interventions and hospital stillbirth rates and
      neonatal mortality.
AB  - BACKGROUND: Previous studies suggest that high risk and low birthweight babies
      have better outcomes if born in hospitals with level III neonatal intensive care
      units. Relations between obstetric care, particularly intrapartum interventions
      and perinatal outcomes, are less well understood, however. OBJECTIVE: To
      investigate effects of obstetric, paediatric, and demographic factors on rates of
      hospital stillbirths and neonatal mortality. METHODS: Cross sectional data on all
      65 maternity units in all Thames Regions, 1994-1996, covering 540 834 live births
      and stillbirths. Hospital level analyses investigated associations between
      staffing rates (consultant/junior paediatricians, consultant/junior
      obstetricians, midwives), facilities (consultant obstetrician/anaesthetist
      sessions, delivery beds, special care baby unit, neonatal intensive care unit
      cots, etc), interventions (vaginal births, caesarean sections, forceps,
      epidurals, inductions, general anaesthetic), parental data (parity, maternal age,
      social class, deprivation, multiple births), and birthweight standardised
      stillbirth rates and neonatal mortality. RESULTS: Unifactorial analyses showed
      consistent negative associations between measures of obstetric intervention and
      stillbirth rates. Some measures of staffing, facilities, and parental data also
      showed significant associations. Scores for interventional, organisational, and
      parental variables were derived for multifactorial analysis to overcome the
      statistical problems caused by high intercorrelations between variables. A higher
      intervention score and higher number of consultant obstetricians per 1000 births
      were both independently and significantly associated with lower stillbirth rates.
      Organisational and parental factors were not significant after adjustment. Only
      Townsend deprivation score was significantly associated with neonatal mortality
      (positive correlation). CONCLUSIONS: Birthweight adjusted stillbirth rates were
      significantly lower in units that took a more interventionalist approach and in
      those with higher levels of consultant obstetric staffing. There were no apparent
      associations between neonatal death rates and the hospital factors measured here.

PMID- 14711858
TI  - Acellular pertussis vaccine given by accelerated schedule: response of preterm
      infants.
AB  - OBJECTIVE: To describe the immune response of preterm infants to a
      diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an
      accelerated schedule, and the effects of steroids on this response. To compare
      responses with those of term infants. DESIGN: Prospective observational study.
      SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics.
      PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP
      Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to
      assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean
      concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean
      gestational age 29.1 weeks) and 54 term infants were recruited. After the third
      immunisation, preterm infants had similar GMCs to controls to diphtheria,
      tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a
      significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN
      increased with age at the third immunisation, and those to tetanus, FHA, PRN, and
      PT increased with gestational age at birth. Response to tetanus correlated
      negatively with the number of doses of antenatal steroids received. There was no
      association between responses and postnatal steroids. CONCLUSION: When immunised
      with a combined acellular pertussis- H influenzae type b vaccine under an
      accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to
      tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to
      tetanus and PRN increased with age at the third immunisation. There is, however,
      no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing
      number of doses of antenatal steroids. There was no effect for postnatal
      steroids.

PMID- 14711859
TI  - Chorioamnionitis increases matrix metalloproteinase-8 concentrations in
      bronchoalveolar lavage fluid from preterm babies.
AB  - OBJECTIVE: To determine the effects of chorioamnionitis and antenatal
      corticosteroids on matrix metalloproteinase-8 (MMP-8) concentrations in
      bronchoalveolar lavage (BAL) fluid from preterm babies in the first week of life.
      DESIGN: Prospective observational study. SETTING: Regional neonatal intensive
      care unit. PATIENTS: Thirty five ventilated preterm babies < 33 weeks gestation,
      seven of whom were born after chorioamnionitis, which was diagnosed
      histologically as the presence of inflammatory cells in the chorioamnionic plate.
      METHODS: MMP-8 was measured by enzyme linked immunosorbent assay (ELISA) in 90
      serial BAL samples taken during the first six postnatal days. The median MMP-8
      concentration for each baby was calculated. RESULTS: Median MMP-8 concentrations
      were higher in the chorioamnionitis group than in those without (43 v 5 ng/ml).
      Partial or complete courses of antenatal corticosteroids had no effect on MMP-8
      concentrations. CONCLUSIONS: Higher concentrations of MMP-8 are found in BAL
      fluid from preterm babies from pregnancies complicated by chorioamnionitis. This
      type I collagenase may contribute to the lung injury that occurs in some babies
      with respiratory distress syndrome.

PMID- 14711860
TI  - Hyperinsulinaemic hypoglycaemia in preterm neonates.
AB  - Hyperinsulinism in infancy (HI) is an important cause of severe and recurrent
      hypoglycaemia in newborn infants. It usually appears in infants born at term, and
      only one case of its occurrence in a prematurely born infant has been reported as
      an incidental finding. This is a report of seven infants born at 31-36 weeks
      gestation who experienced severe persistent hyperinsulinism. Two infants were
      large for dates. All infants were difficult to manage, suggesting that the
      occurrence of HI with prematurity may be associated with a particularly
      aggressive illness. HI should be considered in the differential diagnosis of
      severe hypoglycaemia in preterm infants.

PMID- 14711861
TI  - Characteristics of neonates with isolated rectal bleeding.
AB  - OBJECTIVE: To determine the characteristics of full term and preterm neonates
      with isolated rectal bleeding (IRB), and to follow the outcome of these low risk
      patients. DESIGN: A retrospective case-control study consisting of 147 cases (83
      full term and near term infants and 64 preterm infants) and 147 controls in a
      single institution. RESULTS: A feeding regimen that did not include breast milk
      was the only variable found to predict IRB. In full term and near term babies
      (gestational age >/= 35 weeks), 52.6% of the study group were breast fed compared
      with 83.1% of the controls (p < 0.0001). In preterm babies (gestational age </=
      34 weeks), 45.9% of the study group were breast fed compared with 74.2% of the
      controls (p = 0.0014). No obvious systemic infection cause was detected. None of
      the patients showed clinical or radiological deterioration in the days after
      diagnosis of IRB. CONCLUSIONS: The outcome of a group of low risk neonates with
      IRB was excellent. It is questionable whether antibiotic treatment is required
      and feeding needs to be stopped. Breast feeding, even if only partial, should be
      encouraged.

PMID- 14711862
TI  - Parental concern and distress about infant pain.
AB  - OBJECTIVE: To describe parent views on infant pain care and to explore relations
      between parents' experience of their infant's pain care and parental stress.
      DESIGN: Descriptive, cross sectional survey. SETTING: Nine neonatal units (196
      parents) in the United Kingdom and two neonatal units in the United States (61
      parents). PARTICIPANTS: Parents of preterm and full term infants admitted to
      hospital. INTERVENTIONS: Parents completed a three part questionnaire after the
      second day of the infant's admission and after they had made at least one
      previous visit to see their infant in the neonatal unit. MAIN OUTCOME MEASURES:
      Parent concerns about infant pain; parental stress; parent state and trait
      anxiety. RESULTS: Parents reported that their infants had experienced moderate to
      severe pain that was greater than they had expected (p < 0.001). Few parents (4%)
      received written information, although 58% reported that they received verbal
      information about infant pain or pain management. Only 18% of parents reported
      that they were shown signs of infant pain, but 55% were shown how to comfort
      their infant. Parents had numerous worries about pain and pain treatments.
      Parental stress was independently predicted by parents' estimation of their
      infant's worst pain, worries about pain and its treatment, and dissatisfaction
      with pain information received, after controlling for state anxiety and
      satisfaction with overall care (F = 29.56, df 6, p < 0.001, R(2) = 0.44). The
      findings were similar across sites, despite differences in infant
      characteristics. CONCLUSIONS: Parents have unmet information needs about infant
      pain and wish greater involvement in their infant's pain care. Parent concerns
      about infant pain may contribute to parental stress.

PMID- 14711863
TI  - Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and
      effects of corticosteroids.
AB  - AIMS: To study a longitudinal change in the expression of adhesion molecules
      CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight
      babies who develop respiratory distress syndrome, to compare these levels between
      bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of
      corticosteroid treatment on these adhesion molecules. METHODS: Of 40 eligible
      neonates, 11 neonates were oxygen dependent at 36 weeks (BPD 36 weeks), 16
      infants were oxygen dependent at 28 days, but not at 36 weeks (BPD d28), and 13
      infants did not develop BPD. Seventeen neonates received a six day course of
      steroid treatment. Expression of CD11b, CD18, and CD62L was measured on
      neutrophils and monocytes in arterial blood on days 1, 3, 7, 14, 21, and 28, and
      before and 2-3 days after initiation of dexamethasone treatment by flow
      cytometry. RESULTS: CD18 expression on neutrophils and monocytes and CD62L on
      neutrophils, measured as mean fluorescent intensity, was significantly decreased
      in BPD neonates compared to non-BPD neonates on days 1-28. Dexamethasone
      treatment significantly decreased CD11b, CD18, and CD62L expression on
      neutrophils, and CD11b and CD18L expression on monocytes. CONCLUSIONS: Decreased
      CD18 expression on neutrophils and monocytes, and decreased CD62L expression on
      neutrophils, measured as mean fluorescent intensity during the first four weeks
      of life in micropremies may be risk factors and early predictors of BPD.
      Dexamethasone use was associated with decreased expression of CD11b, CD18, and
      CD62L.

PMID- 14711865
TI  - How safe is intermittent positive pressure ventilation in preterm babies
      ventilated from delivery to newborn intensive care unit?
AB  - OBJECTIVES: To examine whether clinically determined ventilator settings will
      produce acceptable arterial blood gas values on arrival, in preterm infants
      ventilated from delivery to the newborn intensive care unit (NICU). Further, to
      examine the usefulness of tidal volume and minute ventilation measurements at
      this time. DESIGN: A prospective observational cohort study in a tertiary level 3
      NICU. PATIENTS: Twenty six preterm infants requiring intubation and mechanical
      ventilation at the point of delivery to the NICU. SETTING: Infants who required
      mechanical ventilation were monitored with a blinded Ventrak 1550 dynamic lung
      function monitor from the point of delivery to the NICU. A Drager Babylog 2000
      transport ventilator was set up to achieve adequate chest wall movement, and
      FIO(2) was adjusted to achieve preductal SaO(2) of 90-98%. Dynamic lung function
      monitoring data were recorded and related to the arterial blood gas taken on
      arrival. RESULTS: Mean gestation was 28 weeks (range 23-34) and mean birth weight
      was 1180 g (range 480-4200). A quarter (26% (95% confidence interval (CI) 12% to
      48%)) were hypocarbic, with 20% (95% CI 7% to 39%) below 25 mm Hg, and 38% (95%
      CI 20% to 60%) had hyperoxia. Some (20% (95% CI 7% to 39%)) were both hypocarbic
      and hyperoxic. Total minute ventilation per kilogram correlated significantly
      with the inverse of PaCO(2) (p < 0.001). CONCLUSIONS: Clinically determining
      appropriate mechanical ventilation settings from the point of delivery to the
      NICU is difficult, and inadvertent overventilation may be common. Severe
      hyperoxia can occur in spite of adjustment of the FIO(2) concentration to achieve
      an SaO(2) range of 90-98%. Limiting minute ventilation during resuscitation may
      prevent hypocarbia.

PMID- 14711866
TI  - Exhaled nitric oxide in chronically ventilated preterm infants.
AB  - Exhaled nitric oxide (eNO) levels were measured in eight ventilated infants, mean
      gestational age 25.8 (SD 1.7) weeks and postnatal age 55 (SD 39) days, before and
      after three days of dexamethasone treatment. The eNO levels fell from a mean of
      6.5 (SD 3.4) to 4.2 (SD 2.6) parts per billion (p = 0.031) and the mean
      supplementary oxygen levels from 62% to 45% (p = 0.0078).

PMID- 14711867
TI  - Novel genotype of mevalonic aciduria with fatalities in premature siblings.
AB  - Mevalonic aciduria is described in two very low birthweight siblings with
      unspecific clinical signs and recurrent septicaemia. Both died within the first 2
      months of life. DNA analysis showed a novel mutation in the gene encoding
      mevalonate kinase.

PMID- 14711869
TI  - Urinary ascites and anuria caused by bilateral fungal balls in a premature
      infant.
AB  - A case is reported of anuria and urinary ascites secondary to bilateral
      ureteropelvic obstruction by fungal balls. Management consisted of bilateral
      nephrostomy drainage with local irrigation with amphotericin B, and systemic
      antifungal treatment without surgery. Aspiration by paracentesis was performed
      for the urinary ascites and continuous drainage through an 8 Fr pig tail catheter
      for the urinoma. The literature on renal fungus balls in neonates and infants is
      reviewed.

PMID- 14711870
TI  - Cold comfort for babies.

PMID- 14711871
TI  - Haematological consequences of placental insufficiency.

PMID- 14711872
TI  - Senseless represses nuclear transduction of Egfr pathway activation.
AB  - The Epidermal growth factor receptor (Egfr) pathway controls cell fate decisions
      throughout phylogeny. Typically, binding of secreted ligands to Egfr on the cell
      surface initiates a well-described cascade of events that ultimately invokes
      transcriptional changes in the nucleus. In contrast, the mechanisms by which
      autocrine effects are regulated in the ligand-producing cell are unclear. In the
      Drosophila eye, Egfr signaling, induced by the Spitz ligand, is required for
      differentiation of all photoreceptors except for R8, the primary source of Spitz.
      R8 differentiation is instead under the control of the transcription factor
      Senseless. We show that high levels of Egfr activation are incompatible with R8
      differentiation and describe the mechanism by which Egfr signaling is actively
      prevented in R8. Specifically, Senseless does not affect cytoplasmic transduction
      of Egfr activation, but does block nuclear transduction of Egfr activation
      through transcriptional repression of pointed, which encodes the nuclear effector
      of the pathway. Thus, Senseless promotes normal R8 differentiation by preventing
      the effects of autocrine stimulation by Spitz. An analogous relationship exists
      between Senseless and Egfr pathway orthologs in T-lymphocytes, suggesting that
      this mode of repression of Egfr signaling is conserved.

PMID- 14711873
TI  - Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and
      differentiation of impulse-conducting Purkinje fibers in the embryonic heart.
AB  - Impulse-conducting Purkinje fibers differentiate from myocytes during
      embryogenesis. The conversion of contractile myocytes into conduction cells is
      induced by the stretch/pressure-induced factor, endothelin (ET). Active ET is
      produced via proteolytic processing from its precursor by ET-converting enzyme 1
      (ECE1) and triggers signaling by binding to its receptors. In the embryonic chick
      heart, ET receptors are expressed by all myocytes, but ECE1 is predominantly
      expressed in endothelial cells of coronary arteries and endocardium along which
      Purkinje fiber recruitment from myocytes takes place. Furthermore, co-expression
      of exogenous ECE1 and ET-precursor in the embryonic heart is sufficient to
      ectopically convert cardiomyocytes into Purkinje fibers. Thus, localized
      expression of ECE1 defines the site of Purkinje fiber recruitment in embryonic
      myocardium. However, it is not known how ECE1 expression is regulated in the
      embryonic heart. The unique expression pattern of ECE1 in the embryonic heart
      suggests that blood flow-induced stress/stretch may play a role in patterning
      ECE1 expression and subsequent induction of Purkinje fiber differentiation. We
      show that gadolinium, an antagonist for stretch-activated cation channels,
      downregulates the expression of ECE1 and a conduction cell marker, Cx40, in
      ventricular chambers, concurrently with delayed maturation of a ventricular
      conduction pathway. Conversely, pressure-overload in the ventricle by conotruncal
      banding results in a significant expansion of endocardial ECE1 expression and
      Cx40-positive putative Purkinje fibers. Coincident with this, an excitation
      pattern typical of the mature heart is precociously established. These in vivo
      data suggest that biomechanical forces acting on, and created by, the
      cardiovascular system during embryogenesis play a crucial role in Purkinje fiber
      induction and patterning.

PMID- 14711874
TI  - Prep1.1 has essential genetic functions in hindbrain development and cranial
      neural crest cell differentiation.
AB  - In this study we analysed the function of the Meinox gene prep1.1 during
      zebrafish development. Meinox proteins form heterotrimeric complexes with Hox and
      Pbx members, increasing the DNA binding specificity of Hox proteins in vitro and
      in vivo. However, a role for a specific Meinox protein in the regulation of Hox
      activity in vivo has not been demonstrated. In situ hybridization showed that
      prep1.1 is expressed maternally and ubiquitously up to 24 hours post
      fertilization (hpf), and restricted to the head from 48 hpf onwards. Morpholino
      induced prep1.1 loss-of-function caused significant apoptosis in the CNS.
      Hindbrain segmentation and patterning was affected severely, as revealed by
      either loss or defective expression of several hindbrain markers
      (foxb1.2/mariposa, krox20, pax2.1 and pax6.1), including anteriorly expressed Hox
      genes (hoxb1a, hoxa2 and hoxb2), the impaired migration of facial nerve motor
      neurons, and the lack of reticulospinal neurons (RSNs) except Mauthner cells.
      Furthermore, the heads of prep1.1 morphants lacked all pharyngeal cartilages.
      This was not caused by the absence of neural crest cells or their impaired
      migration into the pharyngeal arches, as shown by expression of dlx2 and snail1,
      but by the inability of these cells to differentiate into chondroblasts. Our
      results indicate that prep1.1 has a unique genetic function in craniofacial
      chondrogenesis and, acting as a member of Meinox-Pbc-Hox trimers, it plays an
      essential role in hindbrain development.

PMID- 14711875
TI  - The role of actin cables in directing the morphogenesis of the pharyngeal
      pouches.
AB  - The pharyngeal arches are separated by endodermal outpocketings, the pharyngeal
      pouches. These are structures of considerable importance; they are required to
      segregate the mesenchymal populations of each arch and to induce the formation of
      arch components, and they generate specific derivatives, including the
      parathyroid and the thymus. The pharyngeal pouches are first evident as localised
      sites at which the endoderm contacts the ectoderm, and they then expand along the
      proximodistal axis to generate the narrow, tight morphology of the mature pouch.
      We currently have no knowledge of the morphogenetic mechanisms that direct
      formation of the pharyngeal pouches. Here, in chick, we show that cells within
      the pharyngeal pouch endoderm have an abundance of apically located actin fibres
      that are networked within the endodermal sheet, via their insertion into N
      cadherin adherens junctions, to form a web of supra-cellular actin cables.
      Cytochalasin D disruption of these actin structures results in the formation of
      aberrant pouches that fail to generate their normal slit-like morphology. This
      suggests that the process of pharyngeal pouch morphogenesis involves the
      constraining influence of these actin cables that direct expansion, within the
      pouch, along the proximodistal axis. These results, importantly, provide us with
      vital insights into how the pharyngeal pouches form their normal morphology. They
      also give evidence, for the first time, of actin cables functioning as
      constraints during complex vertebrate morphogenetic episodes.

PMID- 14711876
TI  - Transcriptional regulation of the cardiac-specific MLC2 gene during Xenopus
      embryonic development.
AB  - The mechanisms by which transcription factors, which are not themselves tissue
      restricted, establish cardiomyocyte-specific patterns of transcription in vivo
      are unknown. Nor do we understand how positional cues are integrated to provide
      regionally distinct domains of gene expression within the developing heart. We
      describe regulation of the Xenopus XMLC2 gene, which encodes a regulatory myosin
      light chain of the contractile apparatus in cardiac muscle. This gene is
      expressed from the onset of cardiac differentiation in the frog embryo and is
      expressed throughout all the myocardium, both before and after heart chamber
      formation. Using transgenesis in frog embryos, we have identified an 82 bp
      enhancer within the proximal promoter region of the gene that is necessary and
      sufficient for heart-specific expression of an XMLC2 transgene. This enhancer is
      composed of two GATA sites and a composite YY1/CArG-like site. We show that the
      low-affinity SRF site is essential for transgene expression and that cardiac
      specific expression also requires the presence of at least one adjacent GATA
      site. The overlapping YY1 site within the enhancer appears to act primarily as a
      repressor of ectopic expression, although it may also have a positive role.
      Finally, we show that the frog MLC2 promoter drives pan myocardial expression of
      a transgene in mice, despite the more restricted patterns of expression of murine
      MLC2 genes. We speculate that a common regulatory mechanism may be responsible
      for pan-myocardial expression of XMLC2 in both the frog and mouse, modulation of
      which could have given rise to more restricted patterns of expression within the
      heart of higher vertebrates.

PMID- 14711877
TI  - Drosophila ventral furrow morphogenesis: a proteomic analysis.
AB  - Ventral furrow formation is a key morphogenetic event during Drosophila
      gastrulation that leads to the internalization of mesodermal precursors. While
      genetic analysis has revealed the genes involved in the specification of ventral
      furrow cells, few of the structural proteins that act as mediators of ventral
      cell behavior have been identified. A comparative proteomics approach employing
      difference gel electrophoresis was used to identify more than fifty proteins with
      altered abundance levels or isoform changes in ventralized versus lateralized
      embryos. Curiously, the majority of protein differences between these embryos
      appeared well before gastrulation, only a few protein changes coincided with
      gastrulation, suggesting that the ventral cells are primed for cell shape change.
      Three proteasome subunits were found to differ between ventralized and
      lateralized embryos. RNAi knockdown of these proteasome subunits and time
      dependent difference-proteins caused ventral furrow defects, validating the role
      of these proteins in ventral furrow morphogenesis.

PMID- 14711878
TI  - Expression dynamics of WOX genes mark cell fate decisions during early embryonic
      patterning in Arabidopsis thaliana.
AB  - During embryonic pattern formation, the main body axes are established and cells
      of different developmental fates are specified from a single-cell zygote. Despite
      the fundamental importance of this process, in plants, the underlying mechanisms
      are largely unknown. We show that expression dynamics of novel WOX (WUSCHEL
      related homeobox) gene family members reveal early embryonic patterning events in
      Arabidopsis. WOX2 and WOX8 are co-expressed in the egg cell and zygote and become
      confined to the apical and basal daughter cells of the zygote, respectively, by
      its asymmetric division. WOX2 not only marks apical descendants of the zygote,
      but is also functionally required for their correct development, suggesting that
      the asymmetric division of the plant zygote separates determinants of apical and
      basal cell fates. WOX9 expression is initiated in the basal daughter cell of the
      zygote and subsequently shifts into the descendants of the apical daughter
      apparently in response to signaling from the embryo proper. Expression of WOX5
      shows that identity of the quiescent center is initiated very early in the
      hypophyseal cell, and highlights molecular and developmental similarities between
      the stem cell niches of root and shoot meristems. Together, our data suggest that
      during plant embryogenesis region-specific transcription programs are initiated
      very early in single precursor cells and that WOX genes play an important role in
      this process.

PMID- 14711879
TI  - Nodal and Fgf pathways interact through a positive regulatory loop and synergize
      to maintain mesodermal cell populations.
AB  - Interactions between Nodal/Activin and Fibroblast growth factor (Fgf) signalling
      pathways have long been thought to play an important role in mesoderm formation.
      However, the molecular and cellular processes underlying these interactions have
      remained elusive. Here, we address the epistatic relationships between Nodal and
      Fgf pathways during early embryogenesis in zebrafish. First, we find that Fgf
      signalling is required downstream of Nodal signals for inducing the Nodal co
      factor One-eyed-pinhead (Oep). Thus, Fgf is likely to be involved in the
      amplification and propagation of Nodal signalling during early embryonic stages.
      This could account for the previously described ability of Fgf to render cells
      competent to respond to Nodal/Activin signals. In addition, overexpression data
      shows that Fgf8 and Fgf3 can take part in this process. Second, combining zygotic
      mutations in ace/fgf8 and oep disrupts mesoderm formation, a phenotype that is
      not produced by either mutation alone and is consistent with our model of an
      interdependence of Fgf8 and Nodal pathways through the genetic regulation of the
      Nodal co-factor Oep and the cell propagation of Nodal signalling. Moreover,
      mesodermal cell populations are affected differentially by double loss-of
      function of Zoep;ace. Most of the dorsal mesoderm undergoes massive cell death by
      the end of gastrulation, in contrast to either single-mutant phenotype. However,
      some mesoderm cells are still able to undergo myogenic differentiation in the
      anterior trunk of Zoep;ace embryos, revealing a morphological transition at the
      level of somites 6-8. Further decreasing Oep levels by removing maternal oep
      products aggravates the mesodermal defects in double mutants by disrupting the
      fate of the entire mesoderm. Together, these results demonstrate synergy between
      oep and fgf8 that operates with regional differences and is involved in the
      induction, maintenance, movement and survival of mesodermal cell populations.

PMID- 14711880
TI  - Morphogenesis during Xenopus gastrulation requires Wee1-mediated inhibition of
      cell proliferation.
AB  - Major developmental events in early Xenopus embryogenesis coincide with changes
      in the length and composition of the cell cycle. These changes are mediated in
      part through the regulation of CyclinB/Cdc2 and they occur at the first mitotic
      cell cycle, the mid-blastula transition (MBT) and at gastrulation. In this
      report, we investigate the contribution of maternal Wee1, a kinase inhibitor of
      CyclinB/Cdc2, to these crucial developmental transitions. By depleting Wee1
      protein levels using antisense morpholino oligonucleotides, we show that Wee1
      regulates M-phase entry and Cdc2 tyrosine phosphorylation in early gastrula
      embryos. Moreover, we find that Wee1 is required for key morphogenetic movements
      involved in gastrulation, but is not needed for the induction of zygotic
      transcription. In addition, Wee1 is positively regulated by tyrosine
      autophosphorylation in early gastrula embryos and this upregulation of Wee1
      activity is required for normal gastrulation. We also show that overexpression of
      Cdc25C, a phosphatase that activates the CyclinB/Cdc2 complex, induces
      gastrulation defects that can be rescued by Wee1, providing additional evidence
      that cell cycle inhibition is crucial for the gastrulation process. Together,
      these findings further elucidate the developmental function of Wee1 and
      demonstrate the importance of cell cycle regulation in vertebrate morphogenesis.

PMID- 14711881
TI  - Phenotypic clustering in MPZ mutations.
AB  - Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily with
      single extracellular, transmembrane and cytoplasmic domains. Homotypic
      interactions between extracellular domains of MPZ adhere adjacent myelin wraps to
      each other. MPZ is also necessary for myelin compaction since mice which lack MPZ
      develop severe dysmyelinating neuropathies in which compaction is dramatically
      disrupted. MPZ mutations in humans cause the inherited demyelinating neuropathy
      CMT1B. Some mutations cause the severe neuropathies of infancy designated as
      Dejerine-Sottas disease, while others cause a 'classical' Charcot-Marie-Tooth
      (CMT) disease Type 1B (CMT1B) phenotype with normal early milestones but
      development of disability during the first two decades of life. Still other
      mutations cause a neuropathy that presents in adults, with normal nerve
      conduction velocities, designated as a 'CMT2' form of CMT1B. To correlate the
      phenotype of patients with MPZ mutations with their genotype, we identified and
      evaluated 13 patients from 12 different families with eight different MPZ
      mutations. In addition, we re-analysed the clinical data from 64 cases of CMT1B
      from the literature. Contrary to our expectations, we found that most patients
      presented with either an early onset neuropathy with signs and symptoms prior to
      the onset of walking or a late onset neuropathy with signs and symptoms at around
      age 40 years. Only occasional patients presented with a 'classical' CMT
      phenotype. Correlation of specific MPZ mutations with their phenotypes
      demonstrated that addition of either a charged amino acid or altering a cysteine
      residue in the extracellular domain caused a severe early onset neuropathy.
      Severe neuropathy was also caused by truncation of the cytoplasmic domain or
      alteration of an evolutionarily conserved amino acid. Taken together, these data
      suggest that early onset neuropathy is caused by MPZ mutations that significantly
      disrupt the tertiary structure of MPZ and thus interfere with MPZ-mediated
      adhesion and myelin compaction. In contrast, late onset neuropathy is caused by
      mutations that more subtly alter myelin structure and which probably disrupt
      Schwann cell-axonal interactions.

PMID- 14711882
TI  - Myofibrillar myopathy: clinical, morphological and genetic studies in 63
      patients.
AB  - The term myofibrillar myopathy (MFM) was proposed in 1996 as a non-committal term
      for a pathological pattern of myofibrillar dissolution associated with
      accumulation of myofibrillar degradation products and ectopic expression of
      multiple proteins that include desmin, alphaB-crystallin (alphaBC), dystrophin
      and congophilic amyloid material. Subsequent studies revealed dominant mutations
      in desmin and alphaBC in some MFM patients, and clinical differences between
      kinships. We here review the clinical, structural and genetic features of 63
      unrelated patients diagnosed as having MFM at the Mayo Clinic between 1977 and
      2003. The age of onset was 54 +/- 16 years (mean +/- SD). Weakness was both
      proximal and distal in 77% and proximal only in 13%. Cardiomyopathy was diagnosed
      in 16%. Electro myography revealed a myopathic pattern associated with abnormal
      electrical irritability; 13 patients had abnormal nerve conduction studies but
      four of these had long-standing diabetes. The abnormal muscle fibres are best
      identified in trichrome-stained sections as harbouring amorphous, granular or
      pleomorphic hyaline structures, and vacuoles containing membranous material. The
      hyaline structures are strongly congophilic. Semiquantitative analysis in each
      case indicates that among the abnormal fibres, an average of 90, 75, 75, 70 and
      70% abnormally express myotilin, desmin, alphaBC, dystrophin and beta-amyloid
      precursor protein, respectively. Therefore, immunostains for these proteins, and
      especially for myotilin, are useful adjuncts in the diagnosis of MFM. Electron
      microscopy shows progressive myofibrillar degeneration commencing at the Z-disk,
      accumulation of degraded filamentous material and entrapment of dislocated
      membranous organelles in autophagic vacuoles. In all patients, we searched for
      mutations in desmin and alphaBC, as well as in telethonin, a Z-disk-associated
      protein, or in syncoilin, which together with plectin links desmin to the Z-disk.
      Two of the 63 patients carry truncation mutations in the C-terminal domain of
      alphaBC, four carry missense mutations in the head or tail region of desmin, and
      none carries a mutation in syncoilin or telethonin. Thus, MFM is morphologically
      distinct but genetically heterogeneous. Further advances in defining the
      molecular causes of MFM will probably come from linkage studies of informative
      kinships or from systematic search for mutations in proteins participating in the
      intricate network supporting the Z-disk.

PMID- 14711883
TI  - Does the representation of time depend on the cerebellum? Effect of cerebellar
      stroke.
AB  - Behaviours that appear to depend on processing temporal information are
      frequently disrupted after cerebellar damage. The present study examined the role
      of the cerebellum in explicit timing and its relationship to other psychological
      processes. We hypothesized that if the cerebellum regulates timekeeping
      operations then cerebellar damage should disrupt the perception and the
      reproduction of intervals, since both are thought to be supported by a common
      timekeeper mechanism. Twenty-one patients with cerebellar damage from stroke and
      30 normal controls performed time perception and time reproduction tasks. In the
      time reproduction task, timing variability was decomposed into a central timing
      component (clock variability) and a motor component (motor implementation
      variability). We found impairments only in time reproduction (increased clock
      variability) in patients with medial and lateral damage involving the middle- to
      superior-cerebellar lobules. To explore potential reasons for the temporal
      processing deficits, time reproduction and perception performance were correlated
      with independent measures of attention, working memory, sensory discrimination
      and processing speed. Poorer working memory correlated with increased variability
      in the 'clock' component of time reproduction. In contrast, processing speed
      correlated best with time perception. The results did not support a role for the
      cerebellum in timekeeping operations. Rather, deficits in timing movements may be
      related to a disruption in acquiring sensory and cognitive information relevant
      to the task, coupled with an additional impairment in the motor-output system.

PMID- 14711884
TI  - Monitoring dose response of enzyme replacement therapy in feline
      mucopolysaccharidosis type VI by tandem mass spectrometry.
AB  - Mucopolysaccharidosis type VI is an inherited disorder of glycosaminoglycan
      metabolism characterized by organomegaly, corneal clouding, and skeletal
      dysplasia. Recent developments in the use of tandem mass spectrometry to measure
      sulfated mono- and disaccharides have enabled us to perform noninvasive,
      biochemical monitoring during therapy regimes in mucopolysaccharidosis type VI
      cats in addition to established methods of disease evaluation. In this study,
      mucopolysaccharidosis type VI animals were given high-dose (20 mg/kg) enzyme
      replacement therapy for the first month after birth followed by low doses (1
      mg/kg) for a further 2 mo and were compared with animals maintained on 1 mg/kg
      enzyme replacement therapy for 3 mo. A sulfated monosaccharide (N
      acetylhexosamine) and a sulfated disaccharide (N-acetylhexosamine-uronic acid)
      were elevated in MPS VI cat urine and blood. These markers showed a clear
      discrimination between the treatment groups during the first 4 wk of therapy:
      values in the high-dose group were close to normal whereas those in the low-dose
      group were only slightly lower than the untreated mucopolysaccharidosis type VI
      cats. However, within 2 mo of cessation of the high-dose therapy there was
      minimal difference in the oligosaccharide levels, with both groups lying between
      the untreated and unaffected cats. At the completion of the trial, subjective
      minor improvement was noted in overall physical disease features and also in
      lysosomal vacuolation in tissues from animals on the initial high-dose enzyme
      replacement therapy compared to the low-dose therapy animals. Initial high-dose
      therapy reduced storage load in the animals but had no lasting clinical benefit
      over continuous low-dose therapy.

PMID- 14711885
TI  - Enteral tryptophan requirement determined by oxidation of gastrically or
      intravenously infused phenylalanine is not different from the parenteral
      requirement in neonatal piglets.
AB  - We have recently shown that the requirements of several amino acids differ
      substantially when neonates are fed parenterally as opposed to enterally. Our
      first objective was to determine whether the tryptophan requirement was different
      in parenterally fed (IV(fed)/IV(dose)) versus enterally fed (IG(fed)/IV(dose))
      piglets. Because of the extensive extraction of amino acids by the gut, our other
      objective was to determine whether the route of isotope administration [i.e.
      intragastric (IG(fed)/IG(dose)) versus i.v. (IG(fed)/IV(dose)) dose] affects the
      estimate of tryptophan requirement in enterally fed piglets. We used the
      indicator amino acid oxidation technique in piglets (10 +/- 0.5 d old, 2.79 +/-
      0.28 kg) receiving a complete elemental diet for 6 d either intragastrically or
      intravenously. Piglets were randomly assigned to receive test diets containing
      one of seven levels of tryptophan. All animals received a primed, constant
      infusion of l-[1-(14)C]phenylalanine either parenterally (IV(fed)/IV(dose) and
      IG(fed)/IV(dose)) or enterally (IG(fed)/IG(dose)). The mean tryptophan
      requirements for IV(fed)/IV(dose) (0.145 +/- 0.023 g/kg/d), IG(fed)/IV(dose)
      (0.127 +/- 0.022 g/kg/d), and IG(fed)/IG(dose) (0.113 +/- 0.024 g/kg/d) were
      similar as were the safe intakes (upper 95% confidence interval) (0.185, 0.164,
      0.154 g/kg/d, respectively). These data indicate that tryptophan is not
      extensively used by the gut, in contrast to all the other amino acids we have
      studied. Furthermore, in spite of a splanchnic extraction of 27% of the
      phenylalanine dose, the route of isotope infusion does not affect the tryptophan
      requirement as determined by indicator amino acid oxidation.

PMID- 14711886
TI  - Cortisol infusion decreases renin, but not PGHS-2, EP2, or EP4 mRNA expression in
      the kidney of the fetal sheep at days 109-116.
AB  - Renal prostaglandins (PG), renin, and cortisol are necessary for normal kidney
      development and function during fetal life. We examined the effects of cortisol
      infusion before completion of nephrogenesis (d 109-116 gestation; 2.0-3.0 mg
      hydrocortisone succinate/24 h) on the renal mRNA expression of PGHS-2, the PGE(2)
      receptors, EP(2) and EP(4), and renin in fetal sheep. Cortisol infusion raised
      plasma cortisol levels to 42.8 +/- 6.0 nmol/L compared with saline infusion
      levels of 1.5 +/- 0.5 nmol/L (p < 0.001), but had no effect on fetal body weight,
      proportional kidney mass, or blood gases. Cortisol decreased significantly the
      relative expression of renin mRNA (saline: 0.93 +/- 0.06 units; cortisol: 0.32 +/
      0.03 units, p < 0.05), however it had no effect upon the expression of PGHS-2,
      EP(2), or EP(4) mRNA in fetal sheep kidney. Although there is substantial
      evidence that PGE(2) acting through either the EP(2) or EP(4) receptor stimulates
      renin synthesis in the adult kidney, our results have demonstrated that before
      the completion of nephrogenesis, cortisol down-regulation of renin mRNA
      expression is independent of any change in the expression of PGHS-2, EP(2), or
      EP(4) mRNA expression. During nephrogenesis, the insensitivity of PGHS-2, EP(2),
      and EP(4) expression to down-regulation by cortisol may permit continued PG
      regulation of renal development and urine formation.

PMID- 14711887
TI  - Soluble adhesion molecules and cytokines in children affected by recurrent
      infections of the upper respiratory tract.
AB  - The objective of this study was to compare plasma levels of soluble adhesion
      molecules and Th1-Th2 type cytokines in 44 children with frequently recurrent
      respiratory infections (FRRI) of upper airways, defined as having nine or more
      episodes per year, and in 34 children without recurrence; all subjects were
      followed-up for 12 mo. The viral etiology was determined by cultures from nasal,
      pharyngeal, and ear secretions, using PCR and immunofluorescence. Plasma levels
      of five soluble adhesion molecules (E-selectin, P-selectin, L-selectin,
      intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) and
      interferon (IFN)-gamma, IL-12, IL-4, and IL-10 were measured in patients and in
      15 healthy controls using sandwich ELISA. During acute phase, all patients showed
      significant increase in plasma levels of soluble adhesion molecules; during the
      follow-up, the levels were greater in children with FRRI. A difference of
      cytokine profile was demonstrated between the patients with and without FRRI: an
      increased IL-4 and IL-10 release with decreased levels of IFN-gamma and IL-12
      suggested a skewing into Th2-type response, in patients with FRRI. This pattern
      persisted during the follow-up. In patients without recurrence, an increased IFN
      gamma and IL-12 release, together with decreased levels of IL-4 and IL-10, showed
      a skewing into Th1-type responses; in the follow-up these cytokines reached
      normal values. In conclusion, the abnormal levels of all examined parameters in
      children with FRRI may reflect the persistence of an inflammatory
      microenvironment in the airways and an activation of the immune system that may
      contribute to the frequently recurrence of the respiratory disease.

PMID- 14711888
TI  - Oral glucose before venepuncture relieves neonates of pain, but stress is still
      evidenced by increase in oxygen consumption, energy expenditure, and heart rate.
AB  - Oral glucose was recommended as pain therapy during venepuncture in neonates. It
      is unclear whether this intervention reduces excess oxygen consumption (o(2)),
      energy loss, or cardiovascular destabilization associated with venepuncture, and
      whether <2 mL glucose solution is effective. We tested the hypothesis that oral
      glucose solution attenuates the increases in neonatal oxygen consumption, energy
      expenditure (EE), and heart rate associated with venepuncture for two different
      volumes of glucose solution (2 and 0.4 mL). In this prospective, randomized,
      controlled, double-blind trial, 58 neonates (gestational age, 31-42 wk; postnatal
      age, 1-7 d) were randomized to 2 mL glucose 30%, 0.4 mL glucose 30%, or 2 mL
      water by mouth before venepuncture. The videotaped behavioral pain reactions were
      scored with the Premature Infant Pain Profile. Cry duration, o(2), EE (indirect
      calorimetry), and heart rate were measured. The 2 mL glucose solution reduced
      pain score and crying after venepuncture compared with controls [median pain
      score, 5.5 (interquartile range, 4-9) versus 11 (7-12), p = 0.01; median duration
      of first cry, 0 s (0-43 s) versus 13 s (2-47 s), p < 0.05, respectively]. The 0.4
      mL glucose solution had no effect. The 2 mL glucose solution did not attenuate
      the o(2) increase during venepuncture (1.5 +/- 0.2 mL/kg min (water) versus 1.7
      +/- 0.5 (0.4 mL glucose) versus 1.1 +/- 0.2 (2 mL glucose) (mean +/- SEM) nor EE
      nor heart rate. We conclude that oral administration of 2 mL glucose 30% before
      venepuncture reduced pain expression and crying, but did not prevent the rise in
      o(2), EE, or heart rate. Alternative therapies against the stress of nonpainful
      handling during venepuncture should be explored.

PMID- 14711889
TI  - Development and testing of new screening method for keratan sulfate in
      mucopolysaccharidosis IVA.
AB  - Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease,
      causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We
      developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five
      blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to
      determine whether KS concentration is a suitable marker for early diagnosis and
      longitudinal assessment of disease severity. Blood specimens were obtained from
      patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine
      specimens were also analyzed from patients categorized as severe (n = 56) and
      milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA
      patients were two to eight times higher than those in age-matched controls (15
      323 ng/mL). It was found that blood KS level varied with age and clinical
      severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y
      of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA
      were 1.5 times higher than in the milder form. In contrast to blood, urine KS
      levels in both MPS IVA and controls peaked between 1 and 5 y (15.3 versus 0.26
      mg/g creatinine), and thereafter declined with age. Urine KS level also varied
      with age and clinical severity, and the severe MPS IVA phenotype was associated
      with 6.7 times greater urine KS excretion than the milder one. These findings
      indicate that the new assay for blood or urine KS may be suitable for early
      diagnosis and longitudinal assessment of disease severity in MPS IVA.

PMID- 14711892
TI  - Persistent airway inflammation after resolution of respiratory syncytial virus
      infection in rats.
AB  - Neurogenic inflammation is markedly potentiated in airways that are infected with
      respiratory syncytial virus (RSV). Aims of this study were to determine whether
      this potentiation persists after the virus is cleared, investigate the mechanism
      of postviral potentiation, and define whether prophylaxis with a MAb against the
      RSV fusion protein (palivizumab) prevents this effect. Thirty days after
      inoculation, no evidence of active RSV infection was found in the airway
      epithelium by plaque assay or immunostaining and no viral nucleic sequences were
      detected by PCR, yet capsaicin-induced plasma extravasation in the airways that
      were infected 30 d earlier with RSV was still significantly larger compared with
      pathogen-free controls. Substance P content in lung tissues and capsaicin-induced
      release of this peptide from sensory nerves were significantly increased at 30 d.
      The administration of palivizumab 24 h before virus inoculation prevented the
      development of abnormal neurogenic inflammatory responses. Our data suggest that
      the airways remain abnormally susceptible to the proinflammatory effects of
      sensory nerves after RSV infection is cleared, as a result of changes in sensory
      innervation, and that this abnormality can be prevented by passive prophylaxis
      against RSV.

PMID- 14711893
TI  - Ontogenetic development of rat intestinal bile acid transport requires thyroxine
      but not corticosterone.
AB  - Absorption of bile acids by the distal ileum is an essential component of the
      enterohepatic circulation. In neonatal rats, the appearance of the apical sodium
      dependent bile acid transporter (ASBT) at 17 d of age coincides with increases in
      serum corticosterone and thyroxine. We tested the hypothesis that these hormones
      modulate ASBT expression during ileal development. Taurocholate uptake into the
      isolated ileum of normal 20-d-old pups exhibited saturable (K(m) = 0.52 mM,
      J(max) = 0.34 pmol mg/min) and nonsaturable (K(diff) = 0.015 min(-1)) components
      and was two to five times greater than uptake in the proximal intestine.
      Hypothyroid or euthyroid pups received daily thyroxine injections starting at 6 d
      of age. At 12 d of age, serum concentrations of thyroxine, ileal abundance of
      ASBT mRNA, and ileal rates of taurocholate uptake were low in hypothyroid pups
      that received an injection of vehicle (HT-) or thyroxine (HT+) and in euthyroid
      pups that received an injection of vehicle (ET-) or thyroxine (ET+). At 20 and 26
      d, ileal ASBT mRNA abundance and taurocholate uptake rate remained low in HT-
      pups but increased dramatically in ET- and ET+ pups, paralleling the increase in
      serum thyroxine. Restoration of normal plasma thyroxine in HT- pups by thyroxine
      injections (HT+) restored normal ASBT development. Sodium-glucose co-transporter
      activity and mRNA expression were independent of serum thyroxine levels.
      Corticosterone levels were significantly lower in pups that were adrenalectomized
      at 10 d of age. ASBT mRNA abundance and taurocholate uptake rate increased
      markedly with age but were the same in adrenalectomized, sham-operated, and
      nonoperated pups. Hence, endogenous thyroxine but not corticosterone regulates
      the developmentally timed appearance of ASBT.

PMID- 14711894
TI  - Systemic adrenocorticotropic hormone administration down-regulates the expression
      of corticotropin-releasing hormone (CRH) and CRH-binding protein in infant rat
      hippocampus.
AB  - Systemic adrenocorticotropic hormone (ACTH) administration is a first-line
      therapy for the treatment of infantile spasms, an age-specific seizure disorder
      of infancy. It is proposed that exogenous ACTH acts via negative feedback to
      suppress the synthesis of corticotropin-releasing hormone (CRH), a possible
      endogenous convulsant in infant brain tissue. The aim of this study was to
      determine whether systemic ACTH treatment in infant rats down-regulates the
      hippocampal CRH system, including CRH, CRH-binding protein (CRH-BP), and CRH
      receptors (CRH-R1 and CRH-R2). Daily i.p. injection of ACTH for 7 consecutive
      days (postnatal days 3-9) elevated serum corticosterone levels 20-fold measured
      on postnatal day 10, indicating systemic absorption and circulation of the ACTH.
      Semiquantitative reverse transcriptase-PCR demonstrated that both CRH and CRH-BP
      mRNA obtained from the hippocampi of ACTH-injected infant rats was significantly
      depressed relative to saline-injected animals. Comparable reductions in both CRH
      and CRH-BP synthesis were further demonstrated with radioimmunoassay. In
      contrast, neither CRH-R1 nor CRH-R2 mRNA was altered by ACTH treatment, relative
      to saline-injected rats. This latter finding was confirmed electrophysiologically
      by measuring the enhancement of hippocampal population spikes by exogenous CRH,
      also showing no differences between ACTH- and saline-injected rats. The results
      of this study support the proposal that systemic ACTH treatment down-regulates
      CRH expression in infant brain, perhaps contributing to the therapeutic efficacy
      observed during treatment of infantile spasms.

PMID- 14711895
TI  - Sildenafil, nitric oxide, and acute lung injury: pathophysiology beats
      pharmacotherapy?

PMID- 14711896
TI  - The ketogenic diet: a cautionary note.

PMID- 14711897
TI  - Development of pediatric pulmonology in the United Kingdom, Europe, and
      Australasia.
AB  - The organization of medicine in Europe, the UK and the Commonwealth countries was
      always much less formal than in the USA for many years and pediatricians
      interested in pediatric lung disease and asthma often started off as adult
      internists or specialists in adult pulmonary medicine. The early leaders in
      developing a special interest in the breathing of children during the 1940s and
      1950s were predominantly physiologists and clinicians who began to apply
      physiological techniques to the study lung function in healthy and sick infants
      and children. A major contribution to our understanding of the epidemiology of
      wheezing in children was the early establishment of a cohort study in Australia
      which is still yielding important information. It was during the early 1970s that
      pediatric pulmonary "politics" began to emerge in the UK when pediatricians
      interested in lung diseases began to arrange an informal society and meet
      regularly under the auspices of the British Paediatric Association. In fairly
      characteristic fashion, pulmonology in Europe was represented for a while by
      several different societies but due to the efforts of some dedicated enthusiasts
      there finally emerged the Paediatric Assembly of the European Respiratory Society
      (ERS) and its first Head, Max Zach, went to become President of the ERS itself.
      Despite some early doubts abut the future for pediatric pulmonology as a
      specialty in Europe and Australasia it is clearly flourishing as shown by the
      rising membership of the professional societies and the constant stream of high
      quality basic science and clinical publications.

PMID- 14711898
TI  - Pediatric pulmonology: a developmental history in north america.
AB  - We describe the development of pediatric pulmonology in North America, from its
      rudimentary beginning in the early part of the 20th century. Milestones in the
      history of lung diseases affecting children, such as tuberculosis, cystic
      fibrosis, asthma, and neonatal lung disease, are discussed. Finally, maturation
      into a subspecialty recognized by the American Board of Pediatrics is described.

PMID- 14711899
TI  - Prenatal detection of embryo resorption in osteopontin-deficient mice using
      serial noninvasive magnetic resonance microscopy.
AB  - Appropriate temporal and spatial expression of osteopontin (OPN) in the female
      genital tract may be critical for successful embryo implantation and maintenance
      of gestation. Traditionally, experimental assessments of reproductive success
      have been limited to ex vivo dissection at a single time point to determine
      embryo number and size and are inadequate for ongoing study of the effect(s) of
      genetic manipulation on any individual gestation. To investigate the role of OPN
      in the maintenance of gestation, we developed a noninvasive, in vivo method of
      pregnancy surveillance suitable for murine application using magnetic resonance
      microscopy (MRM). Gravid wild-type mice (n =7) and mice with targeted disruption
      of one or both OPN alleles (OPN(-/-), n = 9; OPN(+/-), n = 3) underwent MRM on
      postcoital days 10.5, 15.5, and 19.5. Prenatal MRM images were used to determine
      embryo numbers and sizes. There were no significant differences in embryo numbers
      determined independently by two blinded observers (mean difference between
      observers = 0.04 embryos; p = 0.87). There was a significant effect of genotype
      on embryo size, with OPN(-/-) embryos significantly smaller at all gestational
      ages. However, targeted disruption of one or more OPN alleles had no effect on
      embryo number at any gestational age. Thus, MRM may be a powerful noninvasive
      method for in vivo prenatal developmental study of genetically engineered mice.

PMID- 14711900
TI  - Interaction between inhaled nitric oxide and intravenous sildenafil in a porcine
      model of meconium aspiration syndrome.
AB  - There has been recent interest in the use of the phosphodiesterase-5 inhibitor
      sildenafil for treating pulmonary hypertension. We examined the interaction
      between inhaled nitric oxide (iNO) and i.v. sildenafil in 12 piglets with acute
      pulmonary hypertension and lung injury secondary to meconium aspiration. Six
      animals (controls) received no intervention after meconium instillation, and six
      received iNO (20 ppm) from 120 min, with the addition at 240 min of an i.v.
      sildenafil infusion (2 mg/kg over 2 h). Meconium instillation increased mean
      pulmonary artery (PA) pressure from 16.0 +/- 3.1 to 24.8 +/- 4.6 mm Hg (p < 0.01)
      and pulmonary vascular resistance (PVR) from 0.047 +/- 0.008 to 0.089 +/- 0.027
      mm Hg. ml(-1). min(-1). kg(-1) (p < 0.01). Oxygenation index increased from 3 +/-
      0.8 to 8.3 +/- 3.0 (p < 0.01). There were no further changes beyond 120 min in
      controls. iNO reduced PA pressure and PVR to baseline values, without influencing
      oxygenation. The addition of sildenafil further reduced PA pressure, tended to
      increase the cardiac output, and reduced PVR from 0.049 +/- 0.02 to 0.028 +/-
      0.01 mm Hg. ml(-1). min(-1). kg(-1) (p < 0.05). Sildenafil lowered the systemic
      blood pressure and systemic vascular resistance and produced profound arterial
      hypoxemia, reducing arterial Po(2) from 69 +/- 23 mm Hg to 49 +/- 15 mm Hg,
      despite substantial increases first in inspired oxygen fraction and subsequently
      in mean airway pressures. Consequently, the oxygenation index increased by 13.9
      +/- 4.8 (p = 0.01). When given in addition to iNO, sildenafil at a dose of >0.5
      mg/kg produced profound pulmonary vasodilation, but this was coupled with an
      unacceptable deterioration in oxygenation and systemic vasodilation in this model
      of pulmonary hypertension with acute parenchymal lung disease.

PMID- 14711901
TI  - Detrimental effects of the ketogenic diet on cognitive function in rats.
AB  - The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet
      that is widely used to treat epilepsy in children. Although the KD has been shown
      to be efficacious in the treatment of childhood epilepsy, the long-term effects
      of the KD on brain development are not clear. The objective of this study was to
      examine the long-term effects of the KD on visual-spatial memory, activity level,
      and emotionality in immature rats after status epilepticus (SE). Weanling rats
      were subjected to lithium/pilocarpine-induced SE or saline injections and were
      then randomized to either the KD or regular rat diet, both fed ad libitum. One
      month later, rats were evaluated for visual-spatial memory in the water maze,
      activity level in the open field test, and emotionality with the handling test.
      Spontaneous recurrent seizures were measured using videotaping, and seizure
      susceptibility was tested with flurothyl inhalation. Brains were weighed and
      examined for mossy fiber sprouting and cell loss. Although rats treated with the
      KD were active and seemed healthy, their weight gain was substantially lower than
      that in rats that received regular rat diet. The KD reduced the number of
      spontaneous seizures but had no discernible effect on flurothyl seizure
      susceptibility. KD-fed rats, with or without SE, had significantly impaired
      visual-spatial learning and memory compared with rats that were fed regular diet.
      The KD had minimal effects on activity level and emotionality. Rats that were
      treated with the KD had significantly impaired brain growth. No differences in
      pathology scores between the KD and regular diet groups were seen after SE.
      Despite reducing the number of spontaneous seizures after SE, the KD resulted in
      severe impairment in visual-spatial memory and decreased brain growth, with no
      effect on mossy fiber sprouting. This study raises concerns about the long-term
      effects of the KD on brain development.

PMID- 14711902
TI  - Potential role of IGF-I in hypoxia tolerance using a rat hypoxic-ischemic model:
      activation of hypoxia-inducible factor 1alpha.
AB  - Hypoxia preconditioning and subsequent tolerance to hypoxia-ischemia damage is a
      well-known phenomenon and has significant implications in clinical medicine. In
      this investigation, we tested the hypothesis that the transcriptional activation
      of IGF-I is one of the underlying mechanisms for hypoxia-induced neuroprotection.
      In a rodent model of hypoxia-ischemia, hypoxia preconditioning improved neuronal
      survival as demonstrated by decreased hypoxia-ischemia-induced neuronal
      apoptosis. To study the role of IGF-I in hypoxia tolerance, we used in situ
      hybridization to examine IGF-I mRNA distribution on adjacent tissue sections. In
      cerebral cortex and hippocampus, hypoxia preconditioning resulted in an increase
      in neuronal IGF-I mRNA levels with or without hypoxia-ischemia. To test its
      direct effects, we added IGF-I to primary neuronal culture under varying oxygen
      concentrations. As oxygen concentration decreased, neuronal survival also
      decreased, which could be reversed by IGF-I, especially at the lowest oxygen
      concentration. Interestingly, IGF-I treatment resulted in an activation of
      hypoxia-inducible factor 1alpha (HIF-1alpha), a master transcription factor for
      hypoxia-induced metabolic adaptation. To evaluate whether IGF-I transcriptional
      activation correlates with HIF-1alpha activity, we studied the time course of HIF
      1alpha DNA binding activity in the same rat model of hypoxia-ischemia. After
      hypoxia-ischemia, there was an increase in HIF-1alpha DNA binding activity in
      cortical tissues, with the highest increase around 24 h. Like IGF-I mRNA levels,
      hypoxia preconditioning increased HIF-1alpha DNA binding activity alone or with
      subsequent hypoxia ischemia. Overall, our results suggest that IGF-I
      transcriptional activation is one of the metabolic adaptive responses to hypoxia,
      which is likely mediated by a direct activation of HIF-1alpha.

PMID- 14711903
TI  - Leukocyte adhesion deficiency in children and Irish setter dogs.
AB  - Children with the genetic immunodeficiency disease leukocyte adhesion deficiency,
      or LAD, develop life-threatening bacterial infections as a result of the
      inability of their leukocytes to adhere to the vessel wall and migrate to the
      sites of infection. Recently, the canine counterpart to LAD, known as canine
      leukocyte adhesion deficiency, or CLAD, has been described in Irish setter dogs.
      This review describes how the clinical phenotype of dogs with CLAD closely
      parallels that of children with the severe deficiency phenotype of LAD, thus
      enabling the CLAD dog to provide a disease-specific, large-animal model for
      testing novel hematopoietic stem cell and gene therapy strategies before their
      translation to children with LAD.

PMID- 14711904
TI  - Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow
      morphology.
AB  - Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive
      metabolic disorder characterized by severe combined immunodeficiency and by
      complex neurologic symptomatology including ataxia, developmental delay, and
      spasticity. Herein we report severe marrow dysplasia in a patient with PNP
      deficiency. Drug-related marrow dysfunction was unlikely, and marrow virological
      studies were negative. A preleukemic myelodysplastic syndrome was also unlikely
      due to normal marrow CD34+ cells, colony growth in clonogenic assay of marrow
      mononuclear cells, apoptosis rate, and Fas expression on marrow nucleated cells,
      as well as morphologic improvement of the marrow dysplasia after normal red blood
      cell transfusion. The patient's marrow stroma showed hypersensitivity to
      irradiation and undetectable PNP enzyme activity similar to peripheral
      lymphocytes. This is the first report of PNP deficiency associated with increased
      lymphocyte and marrow stromal sensitivity to irradiation. We conclude that
      marrows from patients with PNP deficiency might have hypersensitivity to
      irradiation and can develop dysplastic morphology, caused either directly or
      indirectly by the inherited enzymatic defect.

PMID- 14711905
TI  - Estrogen receptor-alpha, sexual dimorphism and reduced-size liver ischemia and
      reperfusion injury in mice.
AB  - Estrogen (E(2)) exerts its effect on target organs principally by interacting
      with specific estrogen receptors (ER) such as ER-alpha or ER-beta. The role that
      these E(2) receptors play in mediating the protective effects observed in RSL+I/R
      induced injury remains to be defined. To study the role of ER-alpha, we
      anesthetized female and male wild type (wt; C57Bl/6) and ER-alpha-deficient
      (alphaERKO) mice and subjected them to 70% liver ischemia for 45 min followed by
      resection of the remaining 30% nonischemic lobes and reperfusion of the ischemic
      tissue. For some experiments, wt and alphaERKO male mice were injected with E(2).
      Survival was monitored on a daily basis while liver injury was assessed by
      quantifying serum alanine aminotransferase (ALT) levels and histopathology.
      Hepatic eNOS mRNA levels were evaluated using semi-quantitative RT-PCR. Our data
      showed that untreated females or males treated with E(2) survived RSL+I/R surgery
      indefinitely whereas all male mice given vehicle died within 3-5 days following
      surgery. This protective effect was diminished in alphaERKO female mice such that
      only 40% of alphaERKO females survived 7 d following RSL+I/R. Furthermore, liver
      injury was significantly higher in alphaERKO females compared with their wt
      counterparts and similar to those seen in wild type males and alphaERKO males.
      The protective effect observed in wild type females or E(2) treated males
      correlated well with increases in hepatic eNOS message whereas both male and
      female alphaERKO mice exhibited significantly lower levels of eNOS mRNA. We
      conclude that this protection may in part be due to the E(2)/ER-alpha-mediated
      activation of eNOS.

PMID- 14711906
TI  - Daily aspirin--only half the answer.

PMID- 14711907
TI  - Folic acid and the prevention of neural-tube defects.

PMID- 14711908
TI  - Peer review and federal regulations.

PMID- 14711909
TI  - A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary
      resuscitation.
AB  - BACKGROUND: Vasopressin is an alternative to epinephrine for vasopressor therapy
      during cardiopulmonary resuscitation, but clinical experience with this treatment
      has been limited. METHODS: We randomly assigned adults who had had an out-of
      hospital cardiac arrest to receive two injections of either 40 IU of vasopressin
      or 1 mg of epinephrine, followed by additional treatment with epinephrine if
      needed. The primary end point was survival to hospital admission, and the
      secondary end point was survival to hospital discharge. RESULTS: A total of 1219
      patients underwent randomization; 33 were excluded because of missing study-drug
      codes. Among the remaining 1186 patients, 589 were assigned to receive
      vasopressin and 597 to receive epinephrine. The two treatment groups had similar
      clinical profiles. There were no significant differences in the rates of hospital
      admission between the vasopressin group and the epinephrine group either among
      patients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or
      among those with pulseless electrical activity (33.7 percent vs. 30.5 percent,
      P=0.65). Among patients with asystole, however, vasopressin use was associated
      with significantly higher rates of hospital admission (29.0 percent, vs. 20.3
      percent in the epinephrine group; P=0.02) and hospital discharge (4.7 percent vs.
      1.5 percent, P=0.04). Among 732 patients in whom spontaneous circulation was not
      restored with the two injections of the study drug, additional treatment with
      epinephrine resulted in significant improvement in the rates of survival to
      hospital admission and hospital discharge in the vasopressin group, but not in
      the epinephrine group (hospital admission rate, 25.7 percent vs. 16.4 percent;
      P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; P=0.002). Cerebral
      performance was similar in the two groups. CONCLUSIONS: The effects of
      vasopressin were similar to those of epinephrine in the management of ventricular
      fibrillation and pulseless electrical activity, but vasopressin was superior to
      epinephrine in patients with asystole. Vasopressin followed by epinephrine may be
      more effective than epinephrine alone in the treatment of refractory cardiac
      arrest.

PMID- 14711910
TI  - Efficacy and safety of low-dose aspirin in polycythemia vera.
AB  - BACKGROUND: The use of aspirin for the prevention of thrombotic complications in
      polycythemia vera is controversial. METHODS: We enrolled 518 patients with
      polycythemia vera, no clear indication for aspirin treatment, and no
      contraindication to such treatment in a double-blind, placebo-controlled,
      randomized trial to assess the safety and efficacy of prophylaxis with low-dose
      aspirin (100 mg daily). The two primary end points were the cumulative rate of
      nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular
      causes and the cumulative rate of nonfatal myocardial infarction, nonfatal
      stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular
      causes. The mean duration of follow-up was about three years. RESULTS: Treatment
      with aspirin, as compared with placebo, reduced the risk of the combined end
      point of nonfatal myocardial infarction, nonfatal stroke, or death from
      cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15
      to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial
      infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or
      death from cardiovascular causes (relative risk, 0.40; 95 percent confidence
      interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality
      were not reduced significantly. The incidence of major bleeding episodes was not
      significantly increased in the aspirin group (relative risk, 1.62; 95 percent
      confidence interval, 0.27 to 9.71). CONCLUSIONS: Low-dose aspirin can safely
      prevent thrombotic complications in patients with polycythemia vera who have no
      contraindications to such treatment.

PMID- 14711911
TI  - A placebo-controlled trial of interferon gamma-1b in patients with idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is a progressive, fatal disease with no
      known efficacious therapy. METHODS: In a double-blind, multinational trial, we
      randomly assigned 330 patients with idiopathic pulmonary fibrosis that was
      unresponsive to corticosteroid therapy to receive subcutaneous interferon gamma
      1b or placebo. RESULTS: Over a median of 58 weeks, interferon gamma-1b therapy
      did not significantly affect the primary end point of progression-free survival,
      defined as the time to disease progression or death, and no significant treatment
      effect was observed on measures of lung function, gas exchange, or the quality of
      life. Ten percent of patients in the interferon gamma-1b group died, as compared
      with 17 percent of patients in the placebo group (P=0.08). Treatment with
      interferon gamma-1b was associated with more frequent constitutional symptoms.
      However, the rates of treatment adherence and premature discontinuation of
      treatment were similar in the two groups. More pneumonias were reported among
      patients in the interferon gamma-1b group, but the incidence of severe or life
      threatening respiratory tract infections was similar in the two groups.
      CONCLUSIONS: In a well-defined population of patients with idiopathic pulmonary
      fibrosis, interferon gamma-1b did not affect progression-free survival, pulmonary
      function, or the quality of life. Owing to the size and duration of the trial, a
      clinically significant survival benefit could not be ruled out.

PMID- 14711912
TI  - Autoantibodies against folate receptors in women with a pregnancy complicated by
      a neural-tube defect.
AB  - BACKGROUND: In the absence of clinical folate deficiency, periconceptional
      supplementation with folic acid reduces a woman's risk of having an infant with a
      neural-tube defect. Since antiserum to folate receptors induces embryo resorption
      and malformations in rats, we hypothesized that autoantibodies against folate
      receptors in women may be associated with pregnancy complicated by a neural-tube
      defect. METHODS: Serum from 12 women who were or had been pregnant with a fetus
      with a neural-tube defect and from 24 control women (20 with current or prior
      normal pregnancies and 4 who were nulligravid) was analyzed for autoantibodies by
      incubation with human placental folate receptors radiolabeled with [3H]folic
      acid. The properties of these autoantibodies were characterized by incubating
      serum and the autoantibodies isolated from serum with placental membranes, ED27
      cells, and KB cells, which express the folate receptors. RESULTS: Serum from 9 of
      12 women with a current or previous affected pregnancy (index subjects) and 2 of
      20 control subjects contained autoantibodies against folate receptors (P<0.001).
      The autoantibodies blocked the binding of [3H]folic acid to folate receptors on
      placental membranes and on ED27 and KB cells incubated at 4 degrees C and blocked
      the uptake of [3H]folic acid by KB cells when incubated at 37 degrees C.
      CONCLUSIONS: Serum from women with a pregnancy complicated by a neural-tube
      defect contains autoantibodies that bind to folate receptors and can block the
      cellular uptake of folate. Further study is warranted to assess whether the
      observed association between maternal autoantibodies against folate receptors and
      neural-tube defects reflects a causal relation.

PMID- 14711914
TI  - Polycystic kidney disease.

PMID- 14711913
TI  - Use of high-cost operative procedures by Medicare beneficiaries enrolled in for
      profit and not-for-profit health plans.
AB  - BACKGROUND: It is widely believed that for-profit health plans are more likely
      than not-for-profit health plans to respond to financial incentives by
      restricting access to care, especially access to high-cost procedures. Until
      recently, data to address this question have been limited. METHODS: We tested the
      hypothesis that the rates of use of 12 common high-cost procedures would be lower
      in for-profit health plans than in not-for-profit plans. Using standardized
      Medicare HEDIS data on 3,726,065 Medicare beneficiaries 65 years of age or older
      who were enrolled in 254 health plans during 1997, we compared for-profit and not
      for-profit plans with respect to rates of cardiac catheterization, coronary
      artery bypass grafting, percutaneous transluminal coronary angioplasty, carotid
      endarterectomy, reduction of femur fracture, total hip replacement, total knee
      replacement, partial colectomy, open cholecystectomy, closed cholecystectomy,
      hysterectomy, and prostatectomy. We adjusted the comparisons for sociodemographic
      case mix and for characteristics of the health plans other than their tax status,
      including the plans' location. RESULTS: The rates of carotid endarterectomy,
      cardiac catheterization, coronary-artery bypass grafting, and percutaneous
      transluminal coronary angioplasty were higher in for-profit health plans than
      they were in not-for-profit health plans; the rates of use of other common costly
      operative procedures were similar in the two types of plan. After adjustment for
      enrollee case mix and other characteristics of the plans, the for-profit plans
      had significantly higher rates than the not-for-profit plans for 2 of the 12
      procedures we studied and had lower rates for none. The geographic locations of
      the health plans did not explain these findings. CONCLUSIONS: Contrary to our
      expectations about the likely effects of financial incentives, the rates of use
      of high-cost operative procedures were not lower among beneficiaries enrolled in
      for-profit health plans than among those enrolled in not-for-profit health plans.

PMID- 14711915
TI  - Images in clinical medicine. Progression of idiopathic pulmonary fibrosis.

PMID- 14711916
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-2004. A 49-year-old woman with asymmetric painful neuropathy.

PMID- 14711917
TI  - Inserting government between patient and physician.

PMID- 14711918
TI  - Vasopressin in asystolic cardiac arrest.

PMID- 14711919
TI  - The elusive goal of therapy for usual interstitial pneumonia.

PMID- 14711920
TI  - Abortion, health, and the law.

PMID- 14711921
TI  - Putting the brakes on cylindromatosis?

PMID- 14711922
TI  - Effects of parathyroid hormone and alendronate alone or in combination in
      osteoporosis.

PMID- 14711923
TI  - D-dimer in venous thromboembolism.

PMID- 14711924
TI  - HHV-8 in pulmonary hypertension.

PMID- 14711925
TI  - Delayed onset of malaria--implications for chemoprophylaxis.

PMID- 14711926
TI  - Fondaparinux for symptomatic pulmonary embolism.

PMID- 14711927
TI  - Melanosis coli?

PMID- 14711928
TI  - Validation of the Harvard Six Cities Study of particulate air pollution and
      mortality.

PMID- 14711929
TI  - Images in clinical medicine. Optic neuritis due to Bartonella henselae infection.

PMID- 14711930
TI  - Suppression of acute herpetic pain-related responses by the kappa-opioid receptor
      agonist (-)-17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-beta-[n-methyl
      3-trans-3-(3-furyl) acrylamido] morphinan hydrochloride (TRK-820) in mice.
AB  - (-)-17-Cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-[N-methyl-3
      trans-3-(3-furyl) acrylamido] morphinan hydrochloride (TRK-820) is a kappa-opioid
      receptor agonist that has pharmacological characteristics different from typical
      kappa-opioid receptor agonists. This study was conducted to determine the
      antiallodynic and antihyperalgesic effects of TRK-820 in a mouse model of acute
      herpetic pain and to compare them with those of the kappa-opioid receptor agonist
      enadoline and the mu-opioid receptor agonist morphine. Percutaneous inoculation
      with herpes simplex virus type-1 induced tactile allodynia and mechanical
      hyperalgesia in the hind paw on the inoculated side. TRK-820 (0.01-0.1 mg/kg
      p.o.), enadoline (1-10 mg/kg p.o.) and morphine (5-20 mg/kg p.o.) dose
      dependently inhibited the allodynia and hyperalgesia, but the antiallodynic and
      antihyperalgesic dose of enadoline markedly decreased spontaneous locomotor
      activity. The antinociceptive action of TRK-820 (0.1 mg/kg) was completely
      antagonized by pretreatment with norbinaltorphimine, a kappa-opioid receptor
      antagonist, but not by naltrexone, a mu-opioid receptor antagonist. Repeated
      treatment with morphine (20 mg/kg, four times) resulted in the reduction of
      antiallodynic and antihyperalgesic effects, whereas the inhibitory potency of TRK
      820 (0.1 mg/kg) was almost the same even after the fourth administration. There
      was no cross-tolerance in antinociceptive activities between TRK-820 and
      morphine. Intrathecal and intracerebroventricular, but not intraplantar,
      injections of TRK-820 (10-100 ng/site) suppressed the allodynia and hyperalgesia.
      These results suggest that TRK-820 inhibits acute herpetic pain through kappa
      opioid receptors in the spinal and supraspinal levels. TRK-820 may have clinical
      efficacy in acute herpetic pain with enough safety margins.

PMID- 14711931
TI  - Application of a kinetic model to the apparently complex behavior of negative and
      positive allosteric modulators of muscarinic acetylcholine receptors.
AB  - The binding of allosteric modulators to G protein-coupled receptors (GPCRs) is
      often described by an equilibrium allosteric ternary complex model (ATCM). This
      study evaluated the effects of three modulators on the binding of [(3)H]N
      methylscopolamine ([(3)H]NMS) to the human M(2) muscarinic acetylcholine receptor
      (mAChR). The binding of each modulator was more complex than predicted by the
      ATCM; the inhibitors heptane-1,7-bis-(dimethyl-3-phthalimidopropyl)-ammonium
      bromide and gallamine yielded biphasic curves that were described empirically by
      a two-site binding model, whereas the enhancer alcuronium yielded a bell-shaped
      curve. Radioligand dissociation assays revealed that the modulators retarded
      [(3)H]NMS kinetics such that the system never attained equilibrium. Subsequent
      application of a kinetic ATCM accommodated and quantified all experimental
      observations. Our findings confirm and extend previous studies on the use of a
      kinetic ATCM for mAChR allosteric enhancers, but also highlight how complex
      curves displayed by allosteric inhibitors can be misinterpreted in terms of
      multisite orthosteric binding. It is possible that similar behavior of other
      allosteric modulators at GPCRs may reflect nonequilibrium binding artifacts
      rather than deviation from an ATCM.

PMID- 14711932
TI  - Protection against cocaine toxicity in mice by the dopamine D3/D2 agonist R-(+)
      trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol
      [(+)-PD 128,907].
AB  - Cocaine abuse is a public health concern with seizures and death being one
      consequence of overdose. In the present study, dopamine D(3/)D(2) receptor
      agonists dose dependently and completely prevented the convulsant and lethal
      effects of cocaine. The D(3)-preferring agonists R-(+)-trans-3,4a,10b-tetrahydro
      4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) [(+)-PD 128,907], (+)-7
      hydroxy-dipropylaminotetralin, and the mixed D(3/)D(2) agonists quinpirole and
      quinelorane were all effective against cocaine toxicity in mice. The
      anticonvulsant effects of these compounds occurred at doses below those that
      produced motor impairment as assessed in the inverted screen test. Protection
      against the convulsant effects of the selective dopamine uptake inhibitor 1-[2
      [bis(4-fluorophenyl)methoxy] ethyl]-4-[3-phenyl-propyl]piperazine (GBR 12909) was
      also conferred by (+)-PD 128,907. The possible selectivity of the effects of (+)
      PD 128,907 (3 mg/kg) for these dopaminergic compounds was demonstrated by its
      general lack of protective efficacy against a host of convulsants acting through
      other neural mechanisms [pentylenetetrazol, (+)-bicuculline, and picrotoxin, 4
      aminopyridine, and t-butylbiclyclophosphoorothionate, N-methyl-d-aspartate,
      kainate, pilocarpine, nicotine, strychnine, aminophylline, threshold electric
      shock, and 6-Hz electrical stimulation]. Direct and correlational evidence
      suggests that these effects were mediated by D(3) receptors. Protection was
      stereospecific and reversible by an antagonist of D(3) receptors [3-[4[1-(4-[2[4
      (3-diethyamino-propoxy)-phenyl]-benzoimidazol-l-yl]-butyl)-1H-benzoimidazol-2-yl]
      phenoxy]-propyl)-diethyl-amine; PD 58491] but not D(2) receptors [3[[4-(4
      chlorophenyl)-4 hydroxypipeidin-1-yl]methyl-1H-indole; L-741,626]. Anticonvulsant
      potencies were positively associated with potencies in a functional assay of D(3)
      but not D(2) receptor function. Together, these findings suggest that the
      prevention of cocaine convulsions and lethality by (+)-PD 128,907 may be due to
      D(3) receptor-mediated events.

PMID- 14711933
TI  - Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3
      adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle.
AB  - The purpose of the present study was to ascertain the role of adenylate (AC)
      versus guanylate cyclase (GC) signaling pathways in the internal anal sphincter
      (IAS) smooth muscle relaxation by beta(1)-, beta(2)-, and beta(3)-adrenoceptor
      (AR) activation by xamoterol, procaterol, and disodium 5-[(2R)-2-(3-chlorophenyl)
      2-hydroxy-ethyl]amino)propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316243),
      respectively. The above-mentioned agonists produced concentration-dependent
      relaxation of the smooth muscle strips. Both the selective G(i/o)alpha and
      G(s)alpha antagonists 8,8'-(carbonylbis(imino-3,1-phenylene))bis-(1,3,5
      naphthalene trisulfonic acid) (NF 023) and 4,4',4",4"'-(carbonylbis(imino-5,1,3
      benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid (NF 449),
      respectively, inhibited the relaxation induced by procaterol. However, only NF
      023 inhibited the relaxation induced by xamoterol and CL 316243. 1H
      [1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, a soluble GC inhibitor, significantly
      inhibited the relaxation induced by different agonists. In contrast, the
      selective AC inhibitor [9-(tetrahydro-2'-furyl)adenine] (SQ 22536) inhibited only
      the relaxation induced by procaterol. (9R,10S,12S)-2,3,9,10,11,12-Hexahydro-10
      hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg: 3',2',1'-kl]pyrrolo[3,4
      l][1,6]benzodiazocine-10-carboxylic acid, hexyl ester (KT 5720), a cAMP-dependent
      protein kinase inhibitor, attenuated the relaxation by procaterol, whereas
      (9S,10R,12R)-2,3,9,10,11,12, hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9.12-epoxy
      1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-I][1,6]benzodiazocine-10-carboxylic
      acid methyl ester (KT 5823), a selective cGMP-dependent protein kinase (PKG)
      inhibitor, attenuated the relaxation induced by xamoterol and CL 316243.
      Xamoterol produced significant increase in cGMP levels, whereas only procaterol
      enhanced the cAMP levels. Western blot analysis confirmed the presence of
      beta(1), beta(2), and beta(3)-AR subtypes in the IAS. In summary, beta(2)-AR
      activates both G(s)alpha and G(i/o)alpha-protein subunits and induces relaxation
      in the rat IAS via both cAMP/cGMP pathways. In contrast, the beta(1)/beta(3)-ARs
      activation causes the smooth muscle relaxation via G(i/o)alpha-protein
      subunit/GC/GMP/PKG pathway. These studies are important for the understanding of
      intracellular mechanisms underlying IAS smooth muscle relaxation and in turn the
      pathophysiology of certain anorectal motility disorders.

PMID- 14711934
TI  - GABA modulates presynaptic signalling mediated by dinucleotides on rat synaptic
      terminals.
AB  - Diadenosine pentaphosphate (Ap(5)A) elicits Ca(2+) transients in isolated rat
      midbrain synaptic terminals acting through specific ionotropic dinucleotide
      receptors. The activation of GABA(B) receptors by baclofen changes the sigmoidal
      concentration-response curve for Ap(5)A (EC(50) = 44 microM) into biphasic
      curves. Thus, when GABA(B) receptors are activated, the curve shows a high
      affinity component in the picomolar range (EC(50) = 77 pM) and a low-affinity
      component in the micromolar range (EC(50) = 17 microM). In addition, in the
      presence of GABA or baclofen, Ap(5)A calcium responses are increased up to 50%
      over the control values. Saclofen, a specific antagonist of GABA(B) receptors,
      blocks the potentiatory effect of baclofen. As occurs with Ap(5)A, GABA(B)
      receptors are also capable to modulate diguanosine pentaphosphate (Gp(5)G)
      induced calcium responses. The combination of immunocytochemical and
      microfluorimetric techniques carried out on single synaptic terminals have shown
      that in the presence of baclofen, 64% of the terminals responding to 100 microM
      Ap(5)A are also able to respond to 100 nM Ap(5)A. This value is close to the
      percentage of synaptic terminals responding to Ap(5)A and labeled with the anti
      GABA(B) receptor antibody (69%). The activity of cyclic AMP-dependent protein
      kinase (PKA) seems to be involved in the potentiatory effect of GABA(B) receptors
      on Ap(5)A calcium responses, because PKA activation by forskolin or dibutiryl
      cyclic AMP blocks the potentiatory effect of baclofen, whereas PKA inhibition
      facilitates calcium signaling mediated by Ap(5)A. These results demonstrate that
      the activation of presynaptic GABA(B) receptors is able to modulate dinucleotide
      responses in synaptic terminals.

PMID- 14711935
TI  - Cardiac ion channel effects of tolterodine.
AB  - Tolterodine is a muscarinic antagonist widely used in the treatment of urinary
      incontinence. Although tolterodine has not been reported to alter cardiac
      repolarization, it is chemically related to other muscarinic antagonists known to
      prolong cardiac repolarization. For this reason, we studied the effects of
      tolterodine on cardiac ion channels and action potential recordings. Using patch
      clamp electrophysiology, we found that tolterodine was a potent antagonist of the
      human ether-a-go-go-related gene (HERG) K(+) channel, displaying an IC(50) value
      of 17 nM. This potency was similar to that observed for the antiarrhythmic drug
      dofetilide (IC(50) of 11 nM). Tolterodine block of HERG displayed a positive
      voltage dependence, suggesting an interaction with an activated state.
      Tolterodine had little effect on the human cardiac Na(+) channel at
      concentrations of up to 1 microM. Inhibition of L-type Ca(2+) currents by
      tolterodine was frequency-dependent with IC(50) values measuring 143 and 1084 nM
      at 1 and 0.1 Hz, respectively. Both tolterodine and dofetilide prolonged action
      potential duration in single guinea pig myocytes over the concentration range of
      3 to 100 nM. However, prolongation was significantly larger for dofetilide
      compared with tolterodine. Tolterodine seems to be an unusual drug in that it
      blocks HERG with high affinity, but produces little QT prolongation clinically.
      Low plasma levels after therapeutic doses combined with mixed ion channel
      effects, most notably Ca(2+) channel blockade, may serve to attenuate the QT
      prolonging effects of this potent HERG channel antagonist.

PMID- 14711936
TI  - Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting.
AB  - There have been a number of reports suggesting inhibition of prostaglandin
      production may impact tumor-mediated wasting and levels of associated humoral
      factors such as hypercalcemia. These reductions were achieved using traditional
      nonsteroidal anti-inflammatory drugs (NSAIDs), which are often contraindicated in
      cancer patients. This is especially true during chemotherapeutic regimens due to
      concerns of bleeding from gastrointestinal and hematopoietic toxicities
      associated with inhibition of the housekeeping cyclooxygenase enzyme COX-1. Here,
      we report that celecoxib, one of the new class of selective COX-2 inhibitors, has
      the potential to reverse tumor-mediated wasting and associated humoral factors
      such as interleukin (IL)-6 and hypercalcemia in preclinical models of cachexia.
      Tumor bearing mice in late stage cachexia regained weight within days of the
      start of celecoxib treatment. Two models were tested. The first was the Colon 26
      (Col26) syngeneic murine model that induces high levels of circulating IL-6 and
      hypercalcemia. The second was the human head and neck 1483 HNSCC xenograft model,
      which is less inflammatory and produces less prostaglandin than Col26. Despite
      the observation that no significant impact on tumor growth was observed between
      vehicle and celecoxib-treated animals over the course of the studies, celecoxib
      rapidly reversed weight loss in both cachectic models. With the added safety of
      celecoxib over traditional NSAIDs, these results suggest a possible therapeutic
      use for celecoxib for treating tumor-mediated wasting.

PMID- 14711937
TI  - Letters to the editor: a change in policy.

PMID- 14711938
TI  - Functional outcome following scapulothoracic dissociation.
AB  - BACKGROUND: Scapulothoracic dissociation is an infrequent injury that is often
      accompanied by neurovascular injuries with a potentially devastating outcome. The
      aim of this study was to evaluate the functional outcome following
      scapulothoracic dissociation. METHODS: During a twenty-four-year period, we
      treated twenty-five patients with a scapulothoracic dissociation. The average age
      was 32.5 years. The average Injury Severity Score was 22 points. Nine patients
      had a complete brachial plexus avulsion, and ten had an incomplete brachial
      plexus avulsion. Three patients died from their associated injuries, and six
      patients required an above-the-elbow amputation. The outcome was assessed with
      use of the Short-Form 36-Item Health Survey, and the shoulder function of the
      patients who had not had an amputation was evaluated with use of the Subjective
      Shoulder Rating System. The degree of initial scapular lateralization was
      quantified with the scapula index. RESULTS: The average duration of follow-up was
      12.6 years. The physical and mental component summary scores and the scores on
      the role-physical, general health, vitality, and mental health subscales of the
      Short-Form 36-Item Health Survey were significantly lower for patients with a
      complete brachial plexus avulsion (p < 0.05). The Subjective Shoulder Rating
      System score was also significantly lower in patients with a complete brachial
      plexus avulsion (33.8 points compared with 72.5 points for the patients with no
      or an incomplete avulsion, p = 0.046). The average scapula index was 1.29 +/-
      0.19. The scores on the Short-Form 36-Item Health Survey scales and the
      Subjective Shoulder Rating System score did not correlate with the initial
      scapula index (p > 0.05). CONCLUSIONS: The presence of a complete brachial plexus
      avulsion is predictive of a poor functional outcome in a patient with a
      scapulothoracic dissociation. Therefore, we suggest a modification of the
      classification of the severity of this injury, with complete brachial plexus
      avulsion considered to be the most severe injury type. LEVEL OF EVIDENCE:
      Prognostic study, Level II-1 (retrospective cohort study). See Instructions to
      Authors for a complete description of levels of evidence.

PMID- 14711939
TI  - The cumulative long-term risk of dislocation after primary Charnley total hip
      arthroplasty.
AB  - BACKGROUND: A widely variable prevalence of dislocation after total hip
      arthroplasty has been reported, partly because of varying durations of follow-up
      for this specific end-point. The effect of demographic factors on the long-term
      risk of dislocation as a function of time after total hip arthroplasty is not
      well understood. The purpose of the present study was to determine the risk of
      dislocation as a function of time after Charnley total hip arthroplasty and to
      investigate the demographic factors that influence the cumulative risk of
      dislocation. METHODS: Six thousand six hundred and twenty-three consecutive
      primary Charnley total hip arthroplasties were performed in 5459 patients at one
      institution between 1969 and 1984. The patients included 2869 female patients and
      2590 male patients with a mean age of sixty-three years. All procedures were
      performed with a 22-mm femoral head, and all femoral and acetabular components
      were fixed with cement. The patients were followed at routine intervals and were
      specifically queried about dislocation. The cumulative risk of dislocation was
      calculated with use of the Kaplan-Meier method. RESULTS: Three hundred and twenty
      hips (4.8%) dislocated. The cumulative risk of a first-time dislocation was 1% at
      one month and 1.9% at one year and then rose at a constant rate of approximately
      1% every five years to 7% at twenty-five years for patients who were alive and
      had not had a revision by that time. Multivariate analysis revealed that the
      relative risk of dislocation for female patients (as compared with male patients)
      was 2.1 and that the relative risk for patients who were seventy years old or
      more (as compared with those who were less than seventy years old) was 1.3. Three
      underlying diagnoses-osteonecrosis of the femoral head, acute fracture or
      nonunion of the proximal part of the femur, and inflammatory arthritis-were
      associated with a significantly greater risk of dislocation than osteoarthritis
      was. CONCLUSIONS: The cumulative long-term risk of dislocation after total hip
      arthroplasty is considerably greater than has been reported in short-term
      studies. The incidence of dislocation is highest in the first year after
      arthroplasty and then continues at a relatively constant rate for the life of the
      arthroplasty. Patients at highest risk are female patients and those with a
      diagnosis of osteonecrosis of the femoral head or an acute fracture or nonunion
      of the proximal part of the femur. LEVEL OF EVIDENCE: Prognostic study, Level II
      1 (retrospective study). See Instructions to Authors for a complete description
      of levels of evidence.

PMID- 14711940
TI  - Response bias: effect on outcomes evaluation by mail surveys after total knee
      arthroplasty.
AB  - BACKGROUND: Mail survey questionnaires are increasingly being used for follow-up
      evaluations to gauge satisfaction and performance after total joint arthroplasty.
      Responses to questionnaires are subject to a variety of possible biases. We
      evaluated response behavior in a mail survey of patients who had had a total knee
      arthroplasty. METHODS: A ten-question survey that evaluated satisfaction, general
      health, and Knee Society knee function and clinical scores was mailed to 472
      patients who had undergone consecutive primary total knee arthroplasties from
      1996 to 1998. The 83% who responded were stratified as early, late, and repeat
      mailing responders. The 17% who failed to respond after two mailings were
      considered nonresponders. All of the nonresponders were eventually contacted. The
      groups were compared with regard to their scores at the preoperative office
      visit, at the most recent office visit, and on the mail survey. RESULTS: In the
      mail survey, the patients who responded earliest gave the highest satisfaction
      ratings and the nonresponders gave the poorest ratings (p < 0.001). Similarly,
      the mean Knee Society knee score (and standard deviation) was significantly
      higher for the early responders (82.7 +/- 19.0) than for the nonresponders (66.9
      +/- 16.0), as was the mean function score (68.8 +/- 24.1 compared with 48.4 +/-
      12.5) and the mean pain score (39.8 +/- 13.9 compared with 27.0 +/- 9.7) (all p <
      0.0001). The change between the preoperative and mail survey Knee Society knee
      scores was significantly higher for the early responders (46.12 +/- 25.71) than
      for the nonresponders (28.45 +/- 23.62), as was the change in the mean function
      scores (18.87 +/- 22.52 compared with 5.34 +/- 20.05) and the change in the mean
      pain scores (23.57 +/- 17.76 compared with 10.67 +/- 12.93) (all p < 0.0001).
      CONCLUSIONS: Patients who do not respond to mail surveys used for follow-up are
      unique in that they report significantly poorer outcomes than do responders. This
      potential response bias should be considered in all follow-up analyses. Because
      it may be difficult to attain 100% response rates in very large series of
      patients, division of the study cohort into more manageable segments is advised
      to achieve a more complete response rate. The assessment of patients who are lost
      to follow-up is an important and necessary component in the accurate analysis of
      outcomes after arthroplasty.

PMID- 14711941
TI  - Factors predictive of outcome after use of the Ponseti method for the treatment
      of idiopathic clubfeet.
AB  - BACKGROUND: The nonoperative technique for the treatment of idiopathic congenital
      talipes equinovarus (clubfoot) described by Ponseti is a popular method, but it
      requires two to four years of orthotic management. The purpose of this study was
      to examine the patient characteristics and demographic factors related to the
      family that are predictive of recurrent foot deformities in patients treated with
      this method. METHODS: The cases of fifty-one consecutive infants with eighty-six
      idiopathic clubfeet treated with use of the Ponseti method were examined
      retrospectively. The patient characteristics at the time of presentation, such as
      the severity of the initial clubfoot deformity, previous treatment, and the age
      at the initiation of treatment, were examined with use of univariate logistic
      regression analysis modeling recurrence. Demographic data on the family,
      including annual income, highest level of education attained by the parents, and
      marital status, as well as parental reports of compliance with the use of the
      prescribed orthosis, were studied in relation to the risk of recurrence. RESULTS:
      The parents of twenty-one patients did not comply with the use of orthotics.
      Noncompliance was the factor most related to the risk of recurrence, with an odds
      ratio of 183 (p < 0.00001). Parental educational level (high-school education or
      less) also was a significant risk factor for recurrence (odds ratio = 10.7, p <
      0.03). With the numbers available, no significant relationship was found between
      gender, race, parental marital status, source of medical insurance, or parental
      income and the risk of recurrence of the clubfoot deformity. In addition, the
      severity of the deformity, the age of the patient at the initiation of treatment,
      and previous treatment were not found to have a significant effect on the risk of
      recurrence. CONCLUSION: Noncompliance and the educational level of the parents
      (high-school education or less) are significant risk factors for the recurrence
      of clubfoot deformity after correction with the Ponseti method. The
      identification of patients who are at risk for recurrence may allow intervention
      to improve the compliance of the parents with regard to the use of orthotics,
      and, as a result, improve outcome. LEVEL OF EVIDENCE: Prognostic study, Level II
      1 (retrospective study). See Instructions to Authors for a complete description
      of levels of evidence.

PMID- 14711942
TI  - Metal-on-metal hybrid surface arthroplasty: two to six-year follow-up study.
AB  - BACKGROUND: Following the reintroduction of metal-on-metal articulating surfaces
      for total hip arthroplasty in Europe in 1988, we developed a surface arthroplasty
      prosthetic system using a metal-on-metal articulation. The present study
      describes the clinical and radiographic results of the first 400 hips treated
      with metal-on-metal hybrid surface arthroplasties at an average follow-up of
      three and a half years. METHODS: Between November 1996 and November 2000, 400
      metal-on-metal hybrid surface arthroplasties were performed in 355 patients. All
      femoral head components were cemented, but only fifty-nine of the short
      metaphyseal stems were cemented. The patients had an average age of forty-eight
      years, 73% were men, and 66% had a diagnosis of osteoarthritis. Clinical and
      radiographic follow-up were performed at three months postoperatively and yearly
      thereafter. RESULTS: The majority of the patients returned to a high level of
      activity, including sports, and 54% had activity scores of >7 on the University
      of California at Los Angeles activity assessment system. Kaplan-Meier
      survivorship curves demonstrated that the rate of survival of the components at
      four years was 94.4%. For patients with a surface arthroplasty risk index score
      of >3, the rate of survival of the components at four years was 89% compared with
      a rate of 97% for those with a score of </=3. The patients with a higher risk
      index were 4.2 times more likely to undergo revision to a total hip replacement
      at four years. Twelve hips (3%) had a revision to a total hip replacement. Seven
      of the twelve hips were revised because of loosening of the femoral component,
      and three were revised because of a femoral neck fracture. Substantial
      radiolucencies were seen around sixteen uncemented metaphyseal femoral stems. No
      femoral radiolucencies were observed among the hips in which the metaphyseal stem
      was cemented. The most important risk factors for femoral component loosening and
      substantial stem radiolucencies were large femoral head cysts (p = 0.029),
      patient height (p = 0.032), female gender (p = 0.005), and smaller component size
      in male patients (p = 0.005). CONCLUSIONS: The preliminary experience with this
      hybrid metal-on-metal bearing is encouraging. Optimal femoral bone preparation
      and component fixation are critical to improving durability. The metal-on-metal
      hybrid surface arthroplasty is easily revised to a standard femoral component if
      necessary. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or
      historical, control group]). See Instructions to Authors for a complete
      description of levels of evidence.

PMID- 14711943
TI  - The biomechanical results of total hip resurfacing arthroplasty.
AB  - BACKGROUND: With the advent of more wear-resistant bearings, there is renewed
      interest in resurfacing total hip arthroplasty. However, there is a paucity of
      information on the biomechanical results of this type of arthroplasty compared
      with those of contemporary total hip arthroplasty. METHODS: Using standardized
      radiographs, we measured and compared the biomechanical parameters that affect
      the hip joint reactive forces in fifty hips that had a metal-metal surface
      replacement with those parameters in forty hips that had a contemporary
      cementless total hip replacement performed during the same time-period by the
      same surgeon. RESULTS: On the average, the arthritic hips that were treated with
      metal-metal surface replacement had had a more valgus preoperative neck-shaft
      angle and less horizontal femoral offset than the normal, contralateral hips (p =
      0.0003). After both the metal-metal surface replacements and the cementless total
      hip replacements, the hip center of rotation was medialized by approximately 6
      mm. Both procedures were associated with an average increase in limb length of
      approximately 3 or 4 mm. After the metal-metal surface replacements, the
      horizontal femoral offset was essentially equal to the preoperative value, but
      both values averaged about 8 mm less than those on the normal, contralateral side
      (p < 0.00001). In the hips with a conventional total hip replacement, the
      horizontal femoral offset increased an average of 9.5 mm compared with the
      preoperative value and was an average of 5 mm more than that for the normal,
      contralateral hip (p = 0.001). CONCLUSIONS: The biomechanical results of total
      hip resurfacing depend on the preoperative anatomy of the proximal part of the
      femur. Limb lengthening of 1 cm can be achieved, but horizontal femoral offset is
      essentially unchanged by hip resurfacing. Horizontal femoral offset can be
      increased reliably with a contemporary total hip replacement. Arthritic hips of
      limbs that are more than 1 cm shorter than the contralateral limb or that have a
      comparatively low horizontal femoral offset may be better served by a
      contemporary total hip replacement. These biomechanical limitations should be
      considered in the selection of hips for resurfacing. LEVEL OF EVIDENCE:
      Therapeutic study, Level III-1 (case-control study). See Instructions to Authors
      for a complete description of levels of evidence.

PMID- 14711944
TI  - The oblique posterior femoral condylar radiographic view following total knee
      arthroplasty.
AB  - BACKGROUND: It is often difficult to evaluate the posterior aspects of the
      femoral condyles after total knee arthroplasty. We have developed an imaging
      technique involving the use of the oblique posterior condylar view for the
      evaluation of the posterior aspects of the femoral condyles. The purpose of the
      present study was to compare the efficacy of this view with that of the true
      lateral view. METHODS: Three orthopaedic surgeons analyzed fifty-five sets of
      radiographs (consisting of oblique posterior condylar and true-lateral views) for
      patients who had undergone total knee arthroplasty. The accuracy and
      reproducibility of the oblique posterior condylar view for the detection of
      radiolucencies were compared with those of the true-lateral view. RESULTS: The
      oblique posterior condylar view was significantly better than the true-lateral
      view for the detection of radiolucencies of the posterior aspects of the femoral
      condyles (p < 0.0005). CONCLUSIONS: Radiographic analysis with use of the oblique
      posterior condylar view is technically easy and is accurate for the evaluation of
      radiolucencies of the posterior aspects of the femoral condyles after total knee
      arthroplasty.

PMID- 14711945
TI  - Utilization of orthopaedic services for hand and wrist conditions in a capitated
      population.
AB  - BACKGROUND: The utilization of orthopaedic services (office visits and surgery)
      to treat hand and wrist conditions is not well known. In this study, we report
      the utilization rates for patients referred for orthopaedic treatment of hand and
      wrist conditions in a large population of individuals enrolled in a capitated
      insurance plan. METHODS: The study population consisted of individuals enrolled,
      between January 1998 and December 2001, in a capitated insurance plan that had an
      annual average membership of 135,188 during that period. This plan was serviced
      by an independent physician association of sixty-two orthopaedic surgeons who
      were responsible for all orthopaedic care. Data were collected prospectively in a
      centralized database as patients with various hand or wrist conditions were
      referred for orthopaedic services. Odds ratios were used to compare gender
      specific and age-specific utilization rates. RESULTS: Overall utilization rates
      were 18.06 office visits and 6.47 surgical procedures per 1000 members per year.
      The most frequent hand or wrist conditions were fractures, carpal tunnel
      syndrome, tendinitis or tenosynovitis, and ganglion or synovial cysts. These four
      diagnoses accounted for 70% of all office visits and 71% of all surgical cases.
      Across all age groups, males had a significantly higher rate of utilization of
      office visits (p < 0.001). Between the ages of thirty-five and fifty-five years,
      utilization of office visits and surgery increased approximately linearly with
      age. CONCLUSIONS: A comparison of these data with those of previous reports
      indicates that approximately one of every ten patients who are referred for
      orthopaedic services has a hand or wrist condition, and nearly half will require
      surgery.

PMID- 14711946
TI  - Clinical factors associated with an increased risk of perioperative blood
      transfusion in nonanemic patients undergoing total hip arthroplasty.
AB  - BACKGROUND: The aim of this study was to identify clinical factors associated
      with an increased need for perioperative blood transfusion in nonanemic patients
      undergoing total hip arthroplasty. METHODS: We evaluated eighty-five consecutive
      nonanemic patients who underwent elective, unilateral, cementless, primary total
      hip arthroplasty and met our inclusion criteria. We attempted to determine
      whether clinical parameters influencing perioperative blood loss, such as age,
      gender, hypertension, and body mass index, were also associated with the need for
      perioperative blood transfusion. RESULTS: Perioperative blood transfusion was
      required in twenty-four (28%) of the eighty-five nonanemic patients. When
      considered alone, age, gender, hypertension, and body mass index were not
      significantly associated with an increased risk of perioperative blood
      transfusion, on the basis of the numbers available. In contrast, there was a
      significantly increased risk of blood transfusion when two or more of these
      clinical parameters were present (p = 0.02). CONCLUSIONS: Our findings indicate
      that clinical variables such as age, gender, hypertension, and body mass index
      may have a synergistic effect on the risk of transfusion in patients undergoing
      elective total hip arthroplasty. The simultaneous analysis of these parameters
      might help to stratify patients with different risks for transfusion and may
      increase the efficiency and reduce the cost of blood-ordering practices
      associated with total hip arthroplasty. LEVEL OF EVIDENCE: Prognostic study,
      Level II-1 (retrospective study). See Instructions to Authors for a complete
      description of levels of evidence.

PMID- 14711947
TI  - Unremitting health-care-utilization outcomes of tertiary rehabilitation of
      patients with chronic musculoskeletal disorders.
AB  - BACKGROUND: Unremitting health-care-seeking behaviors have only infrequently been
      addressed in the literature as an outcome of treatment for chronic disabling work
      related musculoskeletal disorders. The limited research has never focused on the
      patient as the "driver" of health-care utilization, to our knowledge. As a
      result, little attention has been paid to the differences between treated
      patients who seek additional health care from a new provider and those who do
      not. The purpose of this project was to examine the demographic and socioeconomic
      outcome variables that characterize patients with a chronic disabling work
      related musculoskeletal disorder who pursue additional health-care services from
      a new provider following the completion of a tertiary rehabilitation treatment
      program. A prospective comparison cohort design was employed to assess
      characteristics and outcomes of these patients, all of whom were treated with the
      same interdisciplinary protocol. METHODS: A cohort of 1316 patients who had been
      consecutively treated with a rehabilitation program for functional restoration
      was divided into two groups on the basis of whether they had sought treatment
      from a new health-care provider in the year following completion of treatment.
      Group 0 (966 patients) did not visit a new health-care provider for treatment of
      their original occupational injury, and Group 1 (350 patients) visited a new
      provider on at least one occasion. A structured clinical interview to assess
      socioeconomic outcomes was carried out one year after discharge from the
      treatment program; this interview addressed pain, health-care utilization, work
      status, recurrent injury, and whether the Workers' Compensation case had been
      closed. RESULTS: The percentage of Group-0 patients who had undergone pre
      rehabilitation surgery was significantly lower than the percentage of Group-1
      patients who had done so (12% compared with 21%, odds ratio = 1.9 [95% confidence
      interval = 1.3, 2.7]; p < 0.001). One year after treatment, 90% of the Group-0
      patients had returned to work compared with only 78% of the Group-1 patients
      (odds ratio = 2.6 [95% confidence interval, 1.9, 3.6]; p < 0.001). Similarly, 88%
      of the Group-0 patients were still working at one year compared with only 62% of
      the patients in Group 1 (odds ratio = 4.5 [95% confidence interval, 3.3, 6.0]; p
      < 0.001). Whereas 96% of the Group-0 patients had resolved all related legal
      and/or financial disputes by one year, only 77% of the Group-1 patients had done
      so (odds ratio = 6.9 [95% confidence interval, 4.5, 10.5]; p < 0.001). Only a
      negligible percentage (0.4%) of the patients in Group 0 had undergone a new
      operation at the site of the original injury, whereas 12% of the Group-1 patients
      had done so (odds ratio = 31.0 [95% confidence interval, 11.0, 87.3]; p < 0.001).
      When the above outcome variables were analyzed by dividing Group 1 according to
      the number of visits to a new service provider, there was a trend for poorer
      socioeconomic outcomes to be associated with an increasing number of health-care
      visits. CONCLUSIONS: To our knowledge, the present study represents the first
      large-scale examination of patients with a chronic disabling work-related
      musculoskeletal disorder who persist in seeking health-care following the
      completion of tertiary rehabilitation. The results demonstrate that about 25% of
      patients with a chronic disabling work-related musculoskeletal disorder pursue
      new health-care services after completing a course of treatment, and this
      subgroup accounts for a significant proportion of lost worker productivity,
      unremitting disability payments, and excess health-care consumption. LEVEL OF
      EVIDENCE: Prognostic study, Level I-1 (prospective study). See Instructions to
      Authors for a complete description of levels of evidence.

PMID- 14711948
TI  - Lumbar intervertebral body fusion cages: histological evaluation of clinically
      failed cages retrieved from humans.
AB  - BACKGROUND: Although interbody cages are widely used, there is little
      histological documentation of the tissue within cages in the human spine. The
      purpose of this study was to describe the contents of retrieved, clinically
      failed, interbody cages from human patients, with special reference to the
      influence of graft type on the viability of bone in the cages. METHODS: Seventy
      eight cages that had been retrieved from forty-eight patients were analyzed.
      There were eight carbon-fiber cages and seventy threaded metal cages. Of the
      sixty-seven cages for which information about grafting was available, fifty-six
      had been packed with autograft only, six had local autograft mixed with
      demineralized bone matrix, four had allograft, and one had demineralized bone
      matrix only. The indications for cage retrieval included a failed fusion,
      malposition or migration of the cage, trauma (a compression fracture at the
      fusion site), low-back pain, progressive spondylosis, nerve-root impingement,
      and/or infection. The cages had been in situ for an average of twenty-two months.
      Undecalcified sections through the center of each plastic embedded cage were
      reviewed, and the approximate areas occupied by viable bone, necrotic bone,
      fibrocartilage, hyaline cartilage, fibrous tissue, and graft substitute were
      visually estimated. Debris particles were estimated by a semiquantitative scoring
      system. RESULTS: Seventy-one of the seventy-eight cages showed evidence of
      vascular ingrowth and areas of histologically viable bone, representing
      incorporating bone graft. The average area occupied by viable bone was 44%
      (range, 0% to 80%). In some cages, relatively large fragments of cortical bone
      graft were associated with only minimal new-bone formation. Fibrocartilage
      occupied up to 50% of the available area in these failed cages. Some cages also
      contained small fibrocartilage seams connecting segments of bone in a pattern
      that suggested motion in vivo. In thirty-one of the seventy-eight cages, > or =
      5% of the available area was occupied by hyaline cartilage, probably from
      vertebral end plates or facet joints. CONCLUSIONS: While this study was not
      designed to test the efficacy of cages or of bone graft, the prevalence of
      hyaline and fibrocartilage in these failed cages illustrates the importance of
      graft and graft-site preparation to maximize bone-graft incorporation. LEVEL OF
      EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control
      group]). See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 14711949
TI  - Retroviral delivery of Noggin inhibits the formation of heterotopic ossification
      induced by BMP-4, demineralized bone matrix, and trauma in an animal model.
AB  - BACKGROUND: The heterotopic ossification of muscles, tendons, and ligaments is a
      common problem faced by orthopaedic surgeons. We investigated the ability of
      Noggin (a BMP [bone morphogenetic protein] antagonist) to inhibit heterotopic
      ossification. METHODS: Part 1: A retroviral vector carrying the gene encoding
      human Noggin was developed and used to transduce muscle-derived stem cells. Part
      2: Cells transduced with BMP-4 were implanted into both hind limbs of mice along
      with either an equal number, twice the number, or three times the number of
      Noggin-expressing muscle-derived stem cells (treated limb) or with nontransduced
      muscle-derived stem cells (control limb). At four weeks, the mice were killed and
      radiographs were made to look for evidence of heterotopic ossification. Part 3:
      Eighty milligrams of human demineralized bone matrix was implanted into the hind
      limbs of SCID (severe combined immunodeficiency strain) mice along with 100,000,
      500,000, or 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs)
      or nontransduced muscle-derived stem cells (control limbs). At eight weeks, the
      mice were killed and radiographs were made. Part 4: Immunocompetent mice
      underwent bilateral Achilles tenotomy along with the implantation of 1,000,000
      Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced
      muscle-derived stem cells (control limbs). At ten weeks, the mice were killed and
      radiographs were made. RESULTS: Part 1: An in vitro BMP inhibition assay
      demonstrated that Noggin was expressed by muscle-derived stem cells at a level of
      280 ng per million cells per twenty-four hours. Part 2: Three varying doses of
      Noggin-expressing muscle-derived stem cells inhibited the heterotopic
      ossification elicited by BMP-4-expressing muscle-derived stem cells. Heterotopic
      ossification was reduced in a dose-dependent manner by 53%, 74%, and 99%,
      respectively (p < 0.05). Part 3: Each of three varying doses of Noggin-expressing
      muscle-derived stem cells significantly inhibited the heterotopic ossification
      elicited by demineralized bone matrix. Heterotopic ossification was reduced by
      91%, 99%, and 99%, respectively (p < 0.05). Part 4: All eleven animals that
      underwent Achilles tenotomy developed heterotopic ossification at the site of the
      injury in the control limbs. In contrast, the limbs treated with the Noggin
      expressing muscle-derived stem cells had a reduction in the formation of
      heterotopic ossification of 83% and eight of the eleven animals had no
      radiographic evidence of heterotopic ossification (p < 0.05). CONCLUSIONS: The
      delivery of Noggin mediated by muscle-derived stem cells can inhibit heterotopic
      ossification caused by BMP-4, demineralized bone matrix, and trauma in an animal
      model. CLINICAL RELEVANCE: Gene therapy to deliver Noggin may become a powerful
      method to inhibit heterotopic ossification in targeted areas of the body.

PMID- 14711950
TI  - Minimum ten-year follow-up of a straight-stemmed, plasma-sprayed, titanium-alloy,
      uncemented femoral component in primary total hip arthroplasty.
AB  - BACKGROUND: The long-term results of total hip arthroplasty without cement have
      been reported only rarely. The purpose of the present study was to evaluate the
      minimum ten-year results of primary total hip arthroplasty performed with use of
      a proximally porous-coated, plasma-sprayed, straight-stemmed, titanium-alloy
      femoral component. METHODS: The clinical and radiographic results of a
      consecutive series of 105 total hip replacements in ninety-five patients were
      reviewed ten to twelve years postoperatively. The diagnosis was osteoarthritis
      for seventy-seven hips (73%). The clinical result was evaluated on the basis of
      the Harris hip score, complications, and thigh pain. A detailed radiographic
      analysis was performed at each follow-up visit. Kaplan-Meier analysis was
      performed to evaluate the survival of the femoral component. RESULTS: The average
      Harris hip score improved from 46 points preoperatively to 92 points
      postoperatively. The average pain score at the time of the most recent follow-up
      was 42 points, with eighty-three hips (79%) rated as pain-free. Thigh pain was
      identified in only two patients. All radiolucent lines were seen around the tip
      of the stem. All hips had some degree of femoral remodeling consistent with
      osseous ingrowth. No femoral component was revised, and no femoral component had
      evidence of loosening. Eight acetabular components were revised because of
      loosening and wear, and one was revised because of recurrent dislocation. One
      focal femoral osteolytic lesion was seen. CONCLUSIONS: This femoral component
      afforded durable fixation at ten to twelve years after primary total hip
      arthroplasty. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or
      historical, control group]). See Instructions to Authors for a complete
      description of levels of evidence.

PMID- 14711951
TI  - Biomechanical analysis of reconstructions for sternoclavicular joint instability.
AB  - BACKGROUND: A variety of reconstructive methods have been described for the
      treatment of sternoclavicular joint instability, yet none have been analyzed in
      the laboratory, to our knowledge. The purpose of the present study was to
      evaluate three different reconstruction techniques with use of a cadaveric model:
      (1) intramedullary ligament reconstruction, (2) subclavius tendon reconstruction,
      and (3) reconstruction with use of a semitendinosus graft placed in a figure-of
      eight fashion through drill-holes in the clavicle and manubrium. METHODS: Thirty
      six fresh cadaveric specimens were mounted supine on a materials testing machine
      in a custom testing fixture and were subjected to anterior and posterior
      subfailure translation to determine stiffness in the intact state after
      preloading. One of the three reconstruction methods was performed, and the
      specimens were subjected to anterior or posterior translation to failure. Changes
      in stiffness compared with the intact state were analyzed statistically. RESULTS:
      In the anterior direction, the stiffness of the semitendinosus figure-of-eight
      reconstruction was significantly greater than that of the intramedullary ligament
      reconstruction but was not significantly different from that of the subclavius
      tendon reconstruction. The peak load to failure (as defined by translation equal
      to the anteroposterior diameter of the medial head of the clavicle) was 230.3 +/-
      146.1 N for the semitendinosus figure-of-eight reconstruction, 84.6 +/- 45.7 N
      for the intramedullary ligament reconstruction, and 75.6 +/- 19.0 N for the
      subclavius tendon reconstruction. In the posterior direction, the stiffness of
      the semitendinosus figure-of-eight reconstruction was significantly greater than
      those of both of the other reconstructions. The peak load to failure was 241.4 +/
      49.7 N for the semitendinosus figure-of-eight reconstruction, 85.0 +/- 22.8 N
      for the intramedullary ligament reconstruction, and 51.5 +/- 28.9 N for the
      subclavius tendon reconstruction. CONCLUSIONS: The figure-of-eight semitendinosus
      reconstruction for sternoclavicular joint instability has initial biomechanical
      properties that are superior to those of the intramedullary ligament
      reconstruction and subclavius tendon reconstruction techniques. CLINICAL
      RELEVANCE: While it is difficult to extrapolate in vitro data to the clinical
      situation, the figure-of-eight semitendinosus technique has superior initial
      biomechanical properties and may produce improved clinical outcomes in the
      surgical treatment of sternoclavicular joint instability.

PMID- 14711952
TI  - Initial stability of cemented femoral stems as a function of surface finish,
      collar, and stem size.
AB  - BACKGROUND: The optimum surface roughness of cemented femoral stems used for
      total hip replacement is a subject of controversy. While rougher surfaces provide
      stronger cement adhesion, it has been hypothesized that polished, tapered,
      noncollared stems settle into the cement mantle, providing improved stability.
      However, the effects of surface finish on the stability of straight, cemented
      stems tapered only in the coronal plane are not known. METHODS: Using composite
      model femora, we assessed the initial stability of a straight, cemented femoral
      stem as a function of surface roughness, the presence or absence of a collar,
      stem size, and the resultant cement thickness under simulated walking and stair
      climbing loads. Otherwise identical stems were manufactured with polished or
      rough surfaces, with or without a collar, in two different sizes. We isolated
      these three variables and compared their relative contributions to the motion at
      the stem-cement interface throughout cyclic loading. We defined three indicators
      of stability: per-cycle motion, rate of migration, and final migration. RESULTS:
      Surface roughness had a greater influence on per-cycle motions than did the
      presence or absence of a collar or cement thickness. Specifically, in the medial
      lateral direction, per-cycle motion of polished stems was 43 micro m greater than
      that of rough stems (p < 0.01). None of the per-cycle motions decreased over the
      77,000 load cycles. In contrast, with all stems, the rate of migration decreased
      over the course of cyclic loading, but the rate of migration of the polished
      stems was greater than that of the rough stems. Final migrations of the stems
      over the course of loading were generally distal, medial, and into retroversion.
      Compared with rough stems, polished stems had 8 to 18 micro m more axial
      migration (p < 0.001), 48 micro m more anterior-posterior migration (p < 0.001),
      and 0.4 degrees more rotational migration (p = 0.01). CONCLUSIONS: and CLINICAL
      RELEVANCE: The results indicated that, for cemented, straight femoral stems
      tapered only in the coronal plane, a rough surface offers the advantage of less
      per-cycle motion. These results may apply to widely used cemented stem designs
      based on the profile of the original Charnley femoral component, which has
      approximately parallel anterior and posterior aspects.

PMID- 14711953
TI  - Effect of COX-2-specific inhibition on fracture-healing in the rat femur.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory medications have been shown to delay
      fracture-healing. COX-2-specific inhibitors such as celecoxib have recently been
      approved for human use. Our goal was to determine, mechanically, histologically,
      morphologically, and radiographically, whether COX-2-specific inhibition affects
      bone-healing. METHODS: A nondisplaced unilateral fracture was created in the
      right femur of fifty-seven adult male rats. Rats were given no drug, indomethacin
      (1 mg/kg/day), or celecoxib (3 mg/kg/day) daily, starting on postoperative day 1.
      Fractures were analyzed at four, eight, and twelve weeks after creation of the
      fracture. Callus and bridging bone formation was assessed radiographically. The
      amounts of fibrous tissue, cartilage, woven bone, and mature bone formation were
      determined histologically. Morphological changes were assessed to determine
      fibrous healing, callus formation, and bone-remodeling. Callus strength and
      stiffness were assessed biomechanically with three-point bending tests. RESULTS:
      At four weeks, only the indomethacin group showed biomechanical and radiographic
      evidence of delayed healing. Although femora from rats treated with celecoxib
      appeared to have more fibrous tissue than those from untreated rats at four and
      eight weeks, radiographic signs of callus formation, mechanical strength, and
      stiffness did not differ significantly between the groups. By twelve weeks, there
      were no significant differences among the three groups. CONCLUSIONS:
      Postoperative administration of celecoxib, a COX-2-specific inhibitor, did not
      delay healing as seen at twelve weeks following fracture in adult rat femora. At
      four and eight weeks, fibrous healing predominated in the celecoxib group as
      compared with the findings in the untreated group; however, mechanical strength
      and radiographic signs of healing were not significantly inhibited. CLINICAL
      RELEVANCE: Many orthopaedists rely on narcotic analgesia for postfracture and
      postoperative pain, despite deleterious side effects and morbidity. Traditional
      nonsteroidal anti-inflammatory medications have been shown to delay fracture
      union. This effect may be smaller with COX-2-specific inhibitors.

PMID- 14711954
TI  - Comparison of proximal porous-coated and grit-blasted surfaces of hydroxyapatite
      coated stems.
AB  - BACKGROUND: It remains controversial whether a proximal porous coating is
      superior to a grit-blasted surface with regard to providing femoral stem fixation
      in total hip arthroplasty. We examined the hypothesis that a proximal porous
      coating would provide better fixation than would a fully grit-blasted surface of
      otherwise identical proximally hydroxyapatite-coated stems. METHODS: In a
      prospective study, seventeen patients (thirty-four hips) underwent bilateral
      sequential total hip replacement with the Anatomic Porous Replacement at the same
      operation. A proximally porous-coated femoral stem was implanted on one side, and
      a stem of the same design but with a proximal grit-blasted surface was implanted
      in the contralateral hip. A proximal hydroxyapatite coating was applied to the
      metallic substrate of both stems. The patients were followed for a mean 2.5 years
      and then were assessed radiographically and clinically with the Harris hip score.
      RESULTS: With the numbers available, no significant clinical or radiographic
      differences were found between the two cohorts. Thirty of the thirty-four hips
      had an excellent result, two were rated good, and two were rated fair. All hips
      had stable osseous fixation of the stem radiographically. The two types of stems
      were associated with the same pattern of adaptive bone-remodeling. CONCLUSIONS:
      In the first two years following total hip arthroplasty, hydroxyapatite-coated
      proximally porous-coated femoral stems do not provide fixation that is superior
      to that provided by hydroxyapatite-coated grit-blasted stems. LEVEL OF EVIDENCE:
      Therapeutic study, Level II-1 (prospective cohort study). See Instructions to
      Authors for a complete description of levels of evidence.

PMID- 14711955
TI  - Pathogenesis of metaphyseal radiolucent changes following ischemic necrosis of
      the capital femoral epiphysis in immature pigs. A preliminary report.
AB  - BACKGROUND: Although metaphyseal radiolucent changes are often seen in patients
      with Legg-Calve-Perthes disease, the pathogenesis of these changes remains
      controversial. The purpose of the present study was to determine the prevalence
      and histopathological characteristics of these metaphyseal radiolucent changes in
      a piglet model of ischemic necrosis of the capital femoral epiphysis. METHODS:
      Ischemic necrosis of the right femoral head was produced in fifty piglets by
      surgically placing a ligature tightly around the femoral neck. The contralateral,
      left hip of each animal was used as a control. Radiographs and histological
      sections of the femoral heads were examined at two, four, and eight weeks. The
      radiographs were used to measure the femoral neck length in order to assess
      growth disturbance. RESULTS: Thirteen of the fifty animals were found to have
      radiolucent changes in the proximal femoral metaphysis on the side of the
      infarcted femoral head. These changes were observed in none of the twelve animals
      that were evaluated at two weeks, in one of the fourteen animals that were
      evaluated at four weeks, and in twelve of the twenty-four animals that were
      evaluated at eight weeks. The radiolucent changes ranged from a focal cystic
      lesion to a diffuse area of radiolucency around the proximal femoral physis.
      Three distinct types of histological changes were observed in the metaphysis.
      Type-I changes were characterized by focal thickening of the physeal cartilage
      extending down into the metaphysis. Some of these lesions demonstrated cystic
      degeneration of the thickened cartilage. Type-II changes were characterized by
      central disruption of the physis and resorption and replacement of the
      metaphyseal bone in the region by fibrovascular tissue. Type-III changes were
      characterized by diffuse resorption of the physeal cartilage and resorption of
      the adjacent metaphyseal and epiphyseal bone. The mean femoral neck length on the
      infarcted side in animals with metaphyseal radiolucent changes was significantly
      shorter than that in animals without metaphyseal radiolucent changes (p = 0.02).
      CONCLUSIONS: Metaphyseal radiolucent changes frequently were observed in this
      piglet model at eight weeks after the induction of ischemia. The metaphyseal
      radiolucent changes were associated with histopathological lesions of the physis.
      The present study suggests that the presence of metaphyseal lesions can result in
      a greater growth disturbance of the proximal femoral physis than is seen in the
      absence of metaphyseal lesions. CLINICAL RELEVANCE: The present study supports
      the clinical observation that the presence of diffuse metaphyseal radiolucent
      changes may be associated with substantial growth disturbance of the proximal
      part of the femur in patients with Legg-Calve-Perthes disease. The study provides
      a histopathological basis for proximal femoral physeal growth disturbance that
      has not been clearly demonstrated in the past. These findings also may provide a
      histopathological basis for the fluidfilled metaphyseal cysts that sometimes are
      observed on the magnetic resonance imaging scans of these patients.

PMID- 14711957
TI  - Total hip wear debris presenting as lower extremity swelling. A report of two
      cases.

PMID- 14711956
TI  - Prevention of deep-vein thrombosis after total knee arthroplasty in Asian
      patients. Comparison of low-molecular-weight heparin and indomethacin.
AB  - BACKGROUND: A prospective clinical study was performed to compare the efficacy of
      low-molecular-weight heparin and indomethacin for the prevention of deep-vein
      thrombosis after total knee arthroplasty in Asian patients. METHODS: One hundred
      and fifty patients undergoing total knee arthroplasty were randomly divided into
      three groups. One group consisted of fifty-one patients who received no
      prophylaxis with an anticoagulant (the control group), one consisted of fifty
      patients who received the low-molecular-weight heparin Fraxiparine (the
      Fraxiparine group), and the third consisted of forty-nine patients who received
      indomethacin (the indomethacin group). Bilateral ascending venography was
      performed preoperatively and at five, six, or seven days postoperatively. A third
      venogram was made at three months for patients who had had a deep-vein
      thrombosis. RESULTS: The prevalence of deep-vein thrombosis was 71% in the
      control group, 50% in the Fraxiparine group (p = 0.042), and 45% in the
      indomethacin group (p = 0.011). Only 28% of the deep-vein thromboses were
      symptomatic, and there were no pulmonary emboli. CONCLUSIONS: Compared with no
      prophylaxis, Fraxiparine and indomethacin significantly lowered the prevalence of
      deep-vein thrombosis after total knee arthroplasty. Prophylaxis against deep-vein
      thrombosis in the Asian population appears to be warranted. LEVEL OF EVIDENCE:
      Therapeutic study, Level I-1a (randomized controlled trial [significant
      difference]). See Instructions to Authors for a complete description of levels of
      evidence.

PMID- 14711958
TI  - Minocycline-induced blue-green discoloration of bone. A case report.

PMID- 14711959
TI  - Use of magnetic resonance imaging in the diagnosis of an occult fracture of the
      femoral component after total hip arthroplasty. A case report.

PMID- 14711960
TI  - Recurrence of a unicameral bone cyst in the proximal part of the fibula after en
      bloc resection. A case report.

PMID- 14711961
TI  - Desmoid tumor of the subscapularis presenting as isolated loss of external
      rotation of the shoulder. A report of two cases.

PMID- 14711963
TI  - Orthopaedic surgery advances resulting from World War II.

PMID- 14711964
TI  - The orthopaedic surgeon's standard of living versus quality of life.

PMID- 14711965
TI  - Unstable nonunions of the distal part of the humerus.

PMID- 14711966
TI  - Effect of fibular plate fixation on rotational stability of simulated distal
      tibial fractures treated with intramedullary nailing.

PMID- 14711967
TI  - Patellar resurfacing in total knee arthroplasty.

PMID- 14711968
TI  - An AOA critical issue: aging of the North American population: new challenges for
      orthopaedics.

PMID- 14711969
TI  - Lying for the patient's good.

PMID- 14711971
TI  - Representation of an abstract perceptual decision in macaque superior colliculus.
AB  - We recorded from neurons in the intermediate and deep layers of the superior
      colliculus (SC) while monkeys performed a novel direction discrimination task. In
      contrast to the task we used previously, the new version required the monkey to
      dissociate perceptual judgments from preparation to execute specific operant
      saccades. The monkey discriminated between 2 opposed directions of motion in a
      random-dot motion stimulus and was required to maintain the decision in memory
      throughout a delay period before the target of the required operant saccade was
      revealed. We hypothesized that perceptual decisions made in this paradigm would
      be represented in an "abstract" or "categorical" form within the brain, probably
      in the frontal cortex, and that decision-related neural activity would be
      eliminated from spatially organized preoculomotor structures such as the SC. To
      our surprise, however, a small population of neurons in the intermediate and deep
      layers of the SC fired in a choice-specific manner early in the trial well before
      the monkey could plan the operant saccade. Furthermore, the representation of the
      decision during the delay period appeared to be spatial: the active region in the
      SC map corresponded to the region of space toward which the perceptually
      discriminated stimulus motion flowed. Electrical microstimulation experiments
      suggested that these decision-related SC signals were not merely related to
      covert saccade planning. We conclude that monkeys may employ, in part, a
      spatially referenced mnemonic strategy for representing perceptual decisions,
      even when an abstract, categorical representation might appear more likely a
      priori.

PMID- 14711972
TI  - Characterization of wide dynamic range neurons in the deep dorsal horn of the
      spinal cord in preprotachykinin-a null mice in vivo.
AB  - We previously reported that mice with a deletion of the preprotachykinin-A (pptA)
      gene, from which substance P (SP) and neurokinin A (NKA) are derived, exhibit
      reduced behavioral responses to intense stimuli, but that behavioral
      hypersensitivity after injury is unaltered. To understand the contribution of SP
      and NKA to nociceptive transmission in the spinal cord, we recorded single-unit
      activity from wide dynamic range neurons in the lamina V region of the lumbar
      dorsal horn of urethane-anesthetized wild-type and ppt-A null mutant (-/-) mice.
      We found that intensity coding to thermal stimuli was largely preserved in the
      ppt-A -/- mice. Neither the peak stimulus-evoked firing nor the neuronal activity
      during the initial phase (0-4 s) of the 41-49 degrees C thermal stimuli differed
      between the genotypes. However, electrophysiological responses during the late
      phase of the stimulus (5-10 s) and poststimulus (11-25 s) were significantly
      reduced in ppt-A -/- mice. To activate C-fibers and to sensitize the dorsal horn
      neurons we applied mustard oil (MO) topically to the hindpaw. We found that
      neither total MO-evoked activity nor sensitization to subsequent stimuli differed
      between the wild-type and ppt-A -/- mice. However, the time course of the
      sensitization and the magnitude of the poststimulus discharges were reduced in
      ppt-A -/- mice. We conclude that SP and/or NKA are not required for intensity
      coding or sensitization of nociresponsive neurons in the spinal cord, but that
      these peptides prolong thermal stimulus-evoked responses. Thus whereas behavioral
      hypersensitivity after injury is preserved in ppt-A -/- mice, our results suggest
      that the magnitude and duration of these behavioral responses would be reduced in
      the absence of SP and/or NKA.

PMID- 14711973
TI  - Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair
      affective processing in rhesus monkeys.
AB  - The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for
      affective processing. To assess whether there is a hemispheric functional
      specialization for the processing of emotion or reward or both in nonhuman
      primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala
      and PFo in one hemisphere, either left or right, were compared with unoperated
      controls on a battery of tasks that tax affective processing, including two tasks
      that tax reward processing and two that assess emotional reactions. Although the
      two operated groups did not differ from each other, monkeys with unilateral
      lesions, left and right, showed altered reward-processing abilities as evidenced
      by attenuated reinforcer devaluation effects and an impairment in object reversal
      learning relative to controls. In addition, both operated groups showed blunted
      emotional reactions to a rubber snake. By contrast, monkeys with unilateral
      lesions did not differ from controls in their responses to an unfamiliar human
      (human "intruder"). Although the results provide no support for a hemispheric
      specialization of function, they yield the novel finding that unilateral lesions
      of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to
      significantly disrupt affective processing.

PMID- 14711974
TI  - Enhancing encoding of a motor memory in the primary motor cortex by cortical
      stimulation.
AB  - Motor training results in encoding of motor memories, a form of use-dependent
      plasticity. Here we tested the hypothesis that transcranial magnetic stimulation
      (TMS) synchronously applied to a motor cortex engaged in a motor training task
      could enhance this plastic process. Healthy volunteers were studied in four
      sessions: training consisting of performance of directionally specific voluntary
      thumb movements (Train alone), training with TMS delivered during the execution
      of the training movement in a strictly temporal relationship to the motor cortex
      contralateral (Train+TMS synchronous(contra)) and ipsilateral (Train+TMS
      synchronous(ipsi)) to the training hand, and training with TMS delivered
      asynchronous to the training movement to the motor cortex contralateral to the
      training hand (Train+TMS asynchronous(contra)). Train alone, Train+TMS
      synchronous(contra), and Train+TMS asynchronous(contra) but not Train+TMS
      synchronous(ipsi) elicited a clear motor memory. The longevity of the encoded
      memory was significantly enhanced by Train+TMS synchronous(contra) when compared
      with Train alone and Train+TMS asynchronous(contra). Therefore use-dependent
      encoding of a motor memory can be enhanced by synchronous Hebbian stimulation of
      the motor cortex that drives the training task and reduced by stimulation of the
      homologous ipsilateral motor cortex, a result relevant for studies of cognitive
      and physical rehabilitation.

PMID- 14711975
TI  - Ambiguities in sound-duration selectivity by neurons in the inferior colliculus
      of the bat Molossus molossus from Cuba.
AB  - This study examines duration selectivity in auditory neurons of the inferior
      colliculus of the bat Molossus molossus (Molossidae, Chiroptera) from Cuba. Three
      main types of duration selectivity, short-, band-, and long-pass, as previously
      described in other species, are present in M. molossus. The range of best
      durations in the inferior colliculus of this species approximates the durations
      of their echolocation calls, suggesting that, as has been shown in other species
      of bats and frogs, the filter mechanism that produces duration tuning is
      selective for species-specific sounds relevant to behavior. Duration coding in M.
      molossus is not unambiguous because approximately 30% of the short- and band-pass
      neurons respond best to two different stimulus durations. This bimodal duration
      selectivity could be explained by time delayed excitatory inputs that coincide
      with an inhibitory rebound. In addition, the effect of stimulus intensity on
      duration selectivity was tested. For most of the neurons (78%), duration
      selectivity was affected by absolute sound pressure level and/or small changes of
      sound pressure. In this respect, the processing of stimulus duration by
      collicular neurons seems to be more complex in M. molossus than in other species
      studied so far.

PMID- 14711976
TI  - Pursuit-related neurons in the supplementary eye fields: discharge during pursuit
      and passive whole body rotation.
AB  - The primate frontal cortex contains two areas related to smooth-pursuit: the
      frontal eye fields (FEFs) and supplementary eye fields (SEFs). To distinguish the
      specific role of the SEFs in pursuit, we examined discharge of a total of 89
      pursuit-related neurons that showed consistent modulation when head-stabilized
      Japanese monkeys pursued a spot moving sinusoidally in fronto-parallel planes
      and/or in depth and with or without passive whole body rotation. During smooth
      pursuit at different frequencies, 43% of the neurons tested (17/40) exhibited
      discharge amplitude of modulation linearly correlated with eye velocity. During
      cancellation of the vestibulo-ocular reflex and/or chair rotation in complete
      darkness, the majority of neurons tested (91% = 30/33) responded. However, only
      17% of the responding neurons (4/30) were modulated in proportion to gaze (eye-in
      space) velocity during pursuit-vestibular interactions. When the monkeys fixated
      a stationary spot, 20% of neurons tested (7/34) responded to motion of a second
      spot. Among the neurons tested for both smooth-pursuit and vergence tracking (n =
      56), 27% (15/56) discharged during both, 62% (35/56) responded during smooth
      pursuit only, and 11% (6/56) during vergence tracking only. Phase shifts
      (relative to stimulus velocity) of responding neurons during pursuit in frontal
      and depth planes and during chair rotation remained virtually constant (< or =1
      Hz). These results, together with the robust vestibular-related discharge of most
      SEF neurons, show that the discharge of the majority of SEF pursuit-related
      neurons is quite distinct from that of caudal FEF neurons in identical task
      conditions, suggesting that the two areas are involved in different aspects of
      pursuit-vestibular interactions including predictive pursuit.

PMID- 14711977
TI  - Presumed inhibitory neurons in the macaque inferior temporal cortex: visual
      response properties and functional interactions with adjacent neurons.
AB  - Neurons in area TE of the monkey inferior temporal cortex respond selectively to
      images of particular objects or their characteristic visual features. The
      mechanism of generation of the stimulus selectivity, however, is largely unknown.
      This study addresses the role of inhibitory TE neurons in this process by
      examining their visual response properties and interactions with adjacent target
      neurons. We applied cross-correlation analysis to spike trains simultaneously
      recorded from pairs of adjacent neurons in anesthetized macaques. Neurons whose
      activity preceded a decrease in activity from their partner were presumed to be
      inhibitory neurons. Excitatory neurons were also identified as the source neuron
      of excitatory linkage as evidenced by a sharp peak displaced from the 0-ms bin in
      cross-correlograms. Most inhibitory neurons responded to a variety of visual
      stimuli in our stimulus set, which consisted of several dozen geometrical figures
      and photographs of objects, with a clear stimulus preference. On average, 10% of
      the stimuli increased firing rates of the inhibitory neurons. Both excitatory and
      inhibitory neurons exhibited a similar degree of stimulus selectivity. Although
      inhibitory neurons occasionally shared the most preferred stimuli with their
      target neurons, overall stimulus preferences were less similar between adjacent
      neurons with inhibitory linkages than adjacent neurons with common inputs and/or
      excitatory linkages. These results suggest that inhibitory neurons in area TE are
      activated selectively and exert stimulus-specific inhibition on adjacent neurons,
      contributing to shaping of stimulus selectivity of TE neurons.

PMID- 14711978
TI  - Validation of intra-operative detection of paratracheal lymph node metastasis
      using real-time RT-PCR targeting esophageal squamous cell carcinoma.
AB  - BACKGROUND: We previously reported that there was a significant correlation
      between paratracheal lymph node (LN) metastasis and cervical LN metastasis in
      thoracic esophageal squamous cell carcinoma (ESCC) patients. The purpose of this
      study was to establish an intra-operative detection method of LN micrometastasis
      (MM) of ESCC using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC)
      and real-time RT-PCR with a Light Cycler technique, and to evaluate which method,
      or combination of methods, is most suitable for intra-operative detection of
      paratracheal LN MM. METHODS: Under informed consent, we obtained 33 dissected
      paratracheal LN samples from 22 operative patients with ESCC. Afterwards, one LN
      was separated into three parts by a sharp razor, and each part was checked for
      metastasis by HE staining, IHC with anti-cytokeratin antibody and real-time RT
      PCR for SCC mRNA with a Light Cycler. RESULTS: It took 3 h for detection by real
      time RT-PCR, while it took 2 h by IHC. The detection rates of MM by HE staining,
      IHC and real-time RT-PCR were 50.0, 33.3 and 83.3%, respectively. However, there
      was a case of false negative detection that was not detected by IHC or PCR.
      CONCLUSION: The real-time RT-PCR method was useful for intra-operative detection
      of paratracheal LN metastasis. However, combination analysis of HE staining, IHC
      and real-time RT-PCR may be desirable because there was a case of false negative
      detection by IHC and real-time RT-PCR.

PMID- 14711979
TI  - Loss of heterozygosity analyses of asynchronous lesions of ductal carcinoma in
      situ and invasive ductal carcinoma of the human breast.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is known to possess
      characteristics of the pre-invasive stage of breast cancer and is the precursor
      to invasive ductal carcinoma (IDC). However, the natural history of the
      progression from DCIS to IDC remains unknown at the molecular level. METHODS: We
      investigated the loss of heterozygosities (LOHs) in tumors of seven patients with
      a history of breast biopsy. The seven specimens were diagnosed as DCIS on
      histopathological re-examination. These patients were diagnosed with ipsilateral
      breast cancer a few years after biopsy. We used thirteen selected microsatellite
      markers that were mapped to and/or very close to the tumor suppressor genes or
      regions with frequent LOHs in breast cancer. DNA isolated from microdissected
      formalin-fixed, paraffin-embedded tissues was subjected to a PCR-LOH analysis for
      these chromosome loci, and the pattern of LOHs was compared between the two
      asynchronous lesions for the seven cases. RESULTS: In all patients except one,
      the LOHs were concordant at 91% as the informative chromosome loci in cases 1 to
      6 were 56, and the concordance in LOH pattern between DCIS and IDC was detected
      at 50 loci. The LOHs had accumulated in accordance with the tumor progression
      from DCIS to IDC. The recurrent lesion occurred at or near the site of the
      primary biopsy and had similar or identical histopathologic features.
      CONCLUSIONS: These recurrences observed were probably residual disease rather
      than true recurrences. Our results suggest the following: (i) genetic
      alternations accumulate during cancer progression from DCIS to IDC, (ii) DCIS is
      a lesion that has a high risk of developing invasive transformation and (iii)
      after approximately 5 years without treatment, DCIS may develop into IDC.

PMID- 14711980
TI  - The sequencing of radiation therapy and chemotherapy after mastectomy in
      premenopausal women with breast cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prognostic importance of
      the sequencing of radiation therapy and chemotherapy after mastectomy in high
      risk premenopausal women with breast cancer in addition to other known prognostic
      factors in the literature. METHODS: In this retrospective study, 176
      premenopausal women with breast cancer were evaluated. The median age at referral
      was 39 years (range, 28-59 years); 106 patients had stage II and 70 had stage III
      disease. All were subjected to mastectomy. The median number of lymph nodes
      removed was 19. The influence of age, histological grade, number of nodes
      removed, number of positive nodes, tumor size, estrogen receptor status,
      lymphovascular invasion and sequencing of radiotherapy and chemotherapy on 5-year
      locoregional disease-free survival, 5-year systemic disease-free survival, 5-year
      disease-free survival and 5-year cancer-specific survival were studied. RESULTS:
      The 5-year locoregional disease-free survival was 94% for the entire patient
      population. Because of the small number of locoregional recurrences, none of the
      evaluated factors was prognostically significant for locoregional recurrence. The
      5-year systemic disease-free, disease-free and cancer-specific survival rates
      were 72, 70 and 77%, respectively. On multivariate analysis of host, tumor and
      treatment-related factors, the number of positive nodes [RR 1.9 (95% CI: 1.36
      2.63), RR 2 (1.46-2.84 ) and RR 1.8 (1.3-2.71), respectively], histopathological
      grade [RR 1.8 (95% CI: 1.24-2.65), RR 1.9 (1.34-2.88), RR 2.5 (1.65-4.07),
      respectively], estrogen receptor status [RR 3.5 (95% CI: 1.5-8.6), RR 3.9 (1.64
      9.41), RR 2.5 (1.05-6.24), respectively] and the sequencing of radiotherapy and
      chemotherapy [RR 1.6 (95% CI: 1.17-2.39), RR 1.7 (1.25-2.54), RR 1.6 (1.14-2.43),
      respectively] were all significant independent predictors of outcome.
      CONCLUSIONS: Our results show that in addition to traditional prognostic factors,
      the sequencing of radiation therapy and chemotherapy also predict for increased
      risk of any type of recurrence or further tumor death.

PMID- 14711981
TI  - A phase I study of hepatic arterial infusion chemotherapy with zinostatin
      stimalamer alone for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatic arterial infusion of zinostatin stimalamer and lipiodol
      emulsion shows a moderate activity against hepatocellular carcinoma. However, the
      anti-tumor activity of zinostatin stimalamer alone is uncertain. METHODS: The
      primary endpoint was to evaluate the frequency of dose-limiting toxicity and
      determine the maximum-tolerated dose of zinostatin stimalamer when used by intra
      arterial infusion. The candidates for this study were patients with
      hepatocellular carcinoma no longer amenable to established forms of treatment.
      Hepatic arterial infusion chemotherapy was performed by selectively introducing a
      catheter into the hepatic artery with zinostatin stimalamer alone. Treatment was
      repeated at 4-8-week intervals until disease progression or the appearance of
      unacceptable toxicity. The starting dose of zinostatin stimalamer was 3 mg/m(2),
      and doses were increased in 1 mg/m(2) increments in successive cohorts. At least
      three patients were treated at each dose level and three additional patients were
      treated in the presence of dose-limiting toxicity. RESULTS: Twelve patients were
      entered into this trial. Dose-limiting toxicity was observed in one of six
      patients at 3 mg/m(2), and in two of six patients at 4 mg/m(2). The maximum
      tolerated dose was judged to be 3 mg/m(2) with liver dysfunction and serum
      creatinine increase as the dose-limiting toxicity. There was one early death
      suggested to be related to the protocol treatment. None of the 12 patients
      achieved an objective tumor response. CONCLUSION: Hepatic arterial infusion with
      a zinostatin stimalamer of 3 mg/m(2) may be tolerated, but not active, in
      patients with far advanced hepatocellular carcinoma.

PMID- 14711982
TI  - Radical prostatectomy for prostate cancer patients with prostate-specific antigen
      >20 ng/ml.
AB  - OBJECTIVE: Prostate cancer patients with prostate-specific antigen (PSA) >20
      ng/ml are at high risk of progression after radical prostatectomy. Comparison has
      seldom been made between the outcomes of patients with PSA 20.1-50 ng/ml and
      those with PSA >50 ng/ml after radical prostatectomy. We retrospectively analyzed
      the outcomes of these two groups. METHODS: From 1993 to 2002, 60 prostate cancer
      patients receiving radical prostatectomy were enrolled in this study. Thirty
      seven patients with PSA 20.1-50 ng/ml were assigned to Group I. Twenty-three
      patients with PSA >50 ng/ml were assigned to Group II. Preoperatively, Group II
      had greater PSA and PSA density than Group I (P < 0.0001). Group II had higher
      biopsy Gleason score and clinical stage than Group I (P < 0.05). Pathological
      categories and outcomes of both groups were compared. RESULTS: Group II had
      higher Gleason score and tumor volume than Group I (P < 0.05). The incidence of
      organ-confined diseases was 29.7% in Group I and 0% in Group II (P < 0.05). Group
      II had higher incidence of extracapsular tumor extension, positive surgical
      margin and lymph node involvement than Group I (P < 0.05). The incidence of
      postoperative PSA >0.01 ng/ml and PSA failure were higher in Group II than Group
      I (P < 0.05). Need for adjuvant treatment and death from prostate cancer was
      similar in both groups. CONCLUSION: Patients with PSA >50 ng/ml had a poorer
      prognosis than patients with PSA 20.1-50 ng/ml. Those with PSA >50 ng/ml had
      shorter freedom from PSA failure survivals than those with PSA 20.1-50 ng/ml (P =
      0.004). Classification of high-risk prostate patients into two sub-groups with
      PSA 20.1-50 ng/ml and PSA >50 ng/ml should be considered.

PMID- 14711983
TI  - Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with
      advanced stage colorectal cancer.
AB  - OBJECTIVE: In this study, we evaluated the efficacy and tolerability of biweekly
      irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen
      (IFL) in patients with advanced stage colorectal cancer. METHODS: A total of 28
      patients were examined. The median age was 51 years (range, 30-74 years). One
      treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425
      mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every
      4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28
      patients, 18 received the chemotherapy as first line treatment, seven received it
      as second line and three received it as third line. RESULTS: An overall objective
      response rate of 21.5% was achieved in the patient group. However, the overall
      response rate for the 18 patients receiving first line treatment was 27.7%. The
      median response duration was 10.5 months (range, 3-19 months). An additional
      28.6% of the patients had stable disease for a median duration of 6.5 months
      (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1
      22+ months) and median overall survival time was 11+ months (95% confidence
      interval, 9-15 months). Toxicities were mild and manageable. CONCLUSIONS: We
      conclude that biweekly IFL is a practical and tolerable treatment option with a
      disease control rate of 50.1% in patients with advanced stage colorectal cancer.

PMID- 14711984
TI  - Histological complete response in a case of advanced gastric cancer treated by
      chemotherapy with S-1 plus low-dose cisplatin and radiation.
AB  - A 76-year-old male was diagnosed with stage IV (cT4, cN2, cP0, cH0, cM0) gastric
      carcinoma with a type 3 tumor in the cardia with lymph node metastases,
      determined by gastrofiberscope and abdominal computed tomography (CT). The
      patient was treated with chemotherapy consisting of S-1 and low-dose cisplatin
      (CDDP) during the first cycle (3 weeks). S-1 was orally administered at a dose of
      100 mg/day (60 mg/m(2)/day) on days 1-21. CDDP was infused at a dose of 10 mg/day
      (6 mg/m(2)/day) on days 1-5, 8-12 and 15-19. After this cycle, the clinical
      response was evaluated as no change (NC). In the second cycle, radiation therapy
      (2 Gy/day for 5 days/week) was initiated along with the chemotherapy. The CDDP
      dose was decreased to 7.5 mg/day because of the grade 3 thrombocytopenia and
      grade 2 leukocytopenia that occurred during the first cycle. The second cycle was
      stopped at a total radiation dose of 48 Gy due to grade 3 thrombocytopenia and
      grade 2 leukocytopenia. Examination after this treatment showed remarkable
      reduction of tumor volume in the primary lesion and lymph nodes, which was
      defined as a partial response (PR). The patient then underwent total gastrectomy
      with D1 lymph node dissection. The postoperative course was uneventful without
      surgical complications. At this time, no gastric cancer cells were detected in
      the resected specimen, including the primary lesion and lymph nodes, confirming a
      pathological complete response (CR grade 3). Thus, the chemo-radiation treatment
      regimen described here may be a potent tool to control advanced gastric
      carcinoma.

PMID- 14711985
TI  - A new perspective on nerve-sparing radical hysterectomy: nerve topography and
      over-preservation of the cardinal ligament.
AB  - BACKGROUND: Nerve-sparing radical hysterectomy was established by Japanese
      gynecologists. They identified two parts of the cardinal ligament, namely the
      vascular part and the neural part, and postulated that the neural part contained
      the pelvic splanchnic nerves. However, our fresh cadaver studies demonstrated
      that these nerves ran dorsomedially in contrast to the classical concept. The aim
      of this study is to further validate this finding in clinical cases. METHODS: We
      examined the intraoperative biopsy specimens collected from the neural part of
      the cardinal ligament in four patients with cervical carcinoma who underwent
      nerve-sparing radical hysterectomy with dissection of the neural part. RESULTS:
      Careful dissections demonstrated that the pelvic splanchnic nerves arise from the
      dorsomedial side of the neural part at the bottom of the pararectal space. The
      neural part was composed of a connective tissue with focal positive staining by S
      100 protein. CONCLUSIONS: We propose that complete dissection of the cardinal
      ligament should be performed during nerve-sparing hysterectomy to increase its
      radicality.

PMID- 14711986
TI  - Non-invasive management of invasive bladder cancer: lectures by professor William
      U. Shipley.
AB  - This report summarizes lectures by Professor William U. Shipley on the non
      invasive management of invasive bladder cancer with chemoradiotherapy and
      transurethral resection, presented at the 60th Meeting of the International
      Lectureship, in the international lectureship program of the FPCR.

PMID- 14711988
TI  - Mislocalization to the nuclear envelope: an effect of the dystonia-causing
      torsinA mutation.
AB  - Primary dystonia is a disease characterized by involuntary twisting movements
      caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a
      form of primary dystonia caused by an in-frame GAG deletion (DeltaE302/3) in the
      TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We
      show that torsinA is also present in the nuclear envelope (NE), where it appears
      to interact with substrate, and that the DeltaE302/3 mutation causes a striking
      redistribution of torsinA from the endoplasmic reticulum to the NE. In addition,
      DeltaE302/3-torsinA recruits WT torsinA to the NE, potentially providing insight
      into an understanding of the dominant inheritance of the disease. DYT1 dystonia
      appears to be a previously uncharacterized NE disease and the first, to our
      knowledge, to selectively affect CNS function.

PMID- 14711987
TI  - Gene expression profiling identifies clinically relevant subtypes of prostate
      cancer.
AB  - Prostate cancer, a leading cause of cancer death, displays a broad range of
      clinical behavior from relatively indolent to aggressive metastatic disease. To
      explore potential molecular variation underlying this clinical heterogeneity, we
      profiled gene expression in 62 primary prostate tumors, as well as 41 normal
      prostate specimens and nine lymph node metastases, using cDNA microarrays
      containing approximately 26,000 genes. Unsupervised hierarchical clustering
      readily distinguished tumors from normal samples, and further identified three
      subclasses of prostate tumors based on distinct patterns of gene expression. High
      grade and advanced stage tumors, as well as tumors associated with recurrence,
      were disproportionately represented among two of the three subtypes, one of which
      also included most lymph node metastases. To further characterize the clinical
      relevance of tumor subtypes, we evaluated as surrogate markers two genes
      differentially expressed among tumor subgroups by using immunohistochemistry on
      tissue microarrays representing an independent set of 225 prostate tumors.
      Positive staining for MUC1, a gene highly expressed in the subgroups with
      "aggressive" clinicopathological features, was associated with an elevated risk
      of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly
      expressed in the other subgroup, was associated with a decreased risk of
      recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were
      strong predictors of tumor recurrence independent of tumor grade, stage, and
      preoperative prostate-specific antigen levels. Our results suggest that prostate
      tumors can be usefully classified according to their gene expression patterns,
      and these tumor subtypes may provide a basis for improved prognostication and
      treatment stratification.

PMID- 14711989
TI  - Saccharomyces cerevisiae Sin3p facilitates DNA double-strand break repair.
AB  - There are two main pathways in eukaryotic cells for the repair of DNA double
      strand breaks: homologous recombination and nonhomologous end joining. Because
      eukaryotic genomes are packaged in chromatin, these pathways are likely to
      require the modulation of chromatin structure. One way to achieve this is by the
      acetylation of lysine residues on the N-terminal tails of histones. Here we
      demonstrate that Sin3p and Rpd3p, components of one of the predominant histone
      deacetylase complexes of Saccharomyces cerevisiae, are required for efficient
      nonhomologous end joining. We also show that lysine 16 of histone H4 becomes
      deacetylated in the proximity of a chromosomal DNA double-strand break in a Sin3p
      dependent manner. Taken together, these results define a role for the Sin3p/Rpd3p
      complex in the modulation of DNA repair.

PMID- 14711990
TI  - Multiplier operator algebras and applications.
AB  - The one-sided multipliers of an operator space X are a key to "latent operator
      algebraic structure" in X. We begin with a survey of these multipliers, together
      with several of the applications that they have had to operator algebras. We then
      describe several new results on one-sided multipliers, and new applications,
      mostly to one-sided M-ideals.

PMID- 14711991
TI  - Collapse and search dynamics of apomyoglobin folding revealed by submillisecond
      observations of alpha-helical content and compactness.
AB  - The characterization of protein folding dynamics in terms of secondary and
      tertiary structures is important in elucidating the features of intraprotein
      interactions that lead to specific folded structures. Apomyoglobin (apoMb),
      possessing seven helices termed A-E, G, and H in the native state, has a folding
      intermediate composed of the A, G, and H helices, whose formation in the
      submillisecond time domain has not been clearly characterized. In this study, we
      used a rapid-mixing device combined with circular dichroism and small-angle x-ray
      scattering to observe the submillisecond folding dynamics of apoMb in terms of
      helical content (f(H)) and radius of gyration (R(g)), respectively. The folding
      of apoMb from the acid-unfolded state at pH 2.2 was initiated by a pH jump to
      6.0. A significant collapse, corresponding to approximately 50% of the overall
      change in R(g) from the unfolded to native conformation, was observed within 300
      micros after the pH jump. The collapsed intermediate has a f(H) of 33% and a
      globular shape that involves >80% of all its atoms. Subsequently, a stepwise
      helix formation was detected, which was interpreted to be associated with a
      conformational search for the correct tertiary contacts. The characterized
      folding dynamics of apoMb indicates the importance of the initial collapse event,
      which is suggested to facilitate the subsequent conformational search and the
      helix formation leading to the native structure.

PMID- 14711992
TI  - Assessing fitness costs for transgenic Aedes aegypti expressing the GFP marker
      and transposase genes.
AB  - The development of transgenic mosquitoes that are refractory to the transmission
      of human diseases such as malaria, dengue, and yellow fever has received much
      interest due to the ability to transform a number of vector mosquito species with
      transposable elements. Transgenic strains of mosquitoes have been generated with
      molecular techniques that exhibit a reduced capacity to transmit pathogens. These
      advancements have led to questions regarding the fitness of transgenic mosquitoes
      and the ability of transformed mosquitoes to compete and effectively spread
      beneficial genes through nontransformed field populations, the core requirement
      of a genetically based control strategy aimed at reducing the spread of mosquito
      borne human disease. Here we examine the impact of transgenesis on the fitness of
      Aedes aegypti, a mosquito that transmits yellow fever. Mosquitoes were altered
      with two types of transgene, the enhanced GFP gene and two transposase genes from
      the Hermes and MOS1 transposable elements. We examined the effects of these
      elements on the survivorship, longevity, fecundity, sex ratio, and sterility of
      transformed mosquitoes and compared results to the nontransformed laboratory
      strain. We show that demographic parameters are significantly diminished in
      transgenic mosquitoes relative to the untransformed laboratory strain. Reduced
      fitness in transgenic mosquitoes has important implications for the development
      and utilization of this technology for control programs based on manipulative
      molecular modification.

PMID- 14711993
TI  - Hydrogen storage in molecular compounds.
AB  - At low temperature (T) and high pressure (P), gas molecules can be held in ice
      cages to form crystalline molecular compounds that may have application for
      energy storage. We synthesized a hydrogen clathrate hydrate, H(2)(H(2)O)(2), that
      holds 50 g/liter hydrogen by volume or 5.3 wt %. The clathrate, synthesized at
      200-300 MPa and 240-249 K, can be preserved to ambient P at 77 K. The stored
      hydrogen is released when the clathrate is warmed to 140 K at ambient P. Low T
      also stabilizes other molecular compounds containing large amounts of molecular
      hydrogen, although not to ambient P, e.g., the stability field for H(2)(H(2)O)
      filled ice (11.2 wt % molecular hydrogen) is extended from 2,300 MPa at 300 K to
      600 MPa at 190 K, and that for (H(2))(4)CH(4) (33.4 wt % molecular hydrogen) is
      extended from 5,000 MPa at 300 K to 200 MPa at 77 K. These unique characteristics
      show the potential of developing low-T molecular crystalline compounds as a new
      means for hydrogen storage.

PMID- 14711994
TI  - Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma
      cell line.
AB  - Both stem cells and cancer cells are thought to be capable of unlimited
      proliferation. Paradoxically, however, some cancers seem to contain stem-like
      cells (cancer stem cells). To help resolve this paradox, we investigated whether
      established malignant cell lines, which have been maintained for years in
      culture, contain a subpopulation of stem cells. In this article, we show that
      many cancer cell lines contain a small side population (SP), which, in many
      normal tissues, is thought to contain the stem cells of the tissue. We
      demonstrate that in the absence of serum the combination of basic fibroblast
      growth factor and platelet-derived growth factor maintains SP cells in the C6
      glioma cell line. Moreover, we show that C6 SP cells, but not non-SP cells, can
      generate both SP and non-SP cells in culture and are largely responsible for the
      in vivo malignancy of this cell line. Finally, we provide evidence that C6 SP
      cells can produce both neurons and glial cells in vitro and in vivo. We propose
      that many cancer cell lines contain a minor subpopulation of stem cells that is
      enriched in an SP, can be maintained indefinitely in culture, and is crucial for
      their malignancy.

PMID- 14711995
TI  - CO2, not HCO3-, facilitates oxidations by Cu,Zn superoxide dismutase plus H2O2.
AB  - The Cu,Zn superoxide dismutase catalyzes HCO(3)(-) -dependent oxidations by
      H(2)O(2). This activity has been shown to depend on the creation of a bound
      oxidant at the Cu(II) by interactions with H(2)O(2). The bound oxidant was then
      thought to oxidize HCO(3)(-) to CO(3)(.-), which diffuses into the bulk solution
      and there oxidizes diverse substrates. We now find that CO(2) rather than HCO(3)(
      ) facilitates the peroxidations catalyzed by Cu,Zn superoxide dismutase. This
      fact was shown by a lag in the rate of peroxidation of NADPH when NaHCO(3)(-) was
      added last and by a burst in the rate when aqueous CO(2) was added last. Both the
      lag and the burst were eliminated by carbonic anhydrase.

PMID- 14711997
TI  - A form of long-lasting, learning-related synaptic plasticity in the hippocampus
      induced by heterosynaptic low-frequency pairing.
AB  - The late, transcription- and translation-dependent phase of long-term synaptic
      potentiation (L-LTP) at the Schaffer collateral synapse of the hippocampus is an
      experimental model of the synaptic plasticity underlying long-lasting memory
      formation. L-LTP is typically induced by homosynaptic tetanic stimulation; but
      associative forms of learning are likely to require the heterosynaptic pairing of
      stimuli. Here we describe L-LTP elicited by such heterosynaptic pairing at the
      Schaffer collateral synapse in mice. We find that repeated stimulation of one
      pathway at low frequency (0.2 Hz), which does not by itself induce synaptic
      potentiation, will produce long-lasting synaptic plasticity when paired with a
      brief conditioning burst applied to an independent afferent pathway. The
      induction of heterosynaptic L-LTP is associative and critically depends on the
      precise time interval of pairing: simultaneous, conjunctional pairing induces L
      LTP; in contrast, delayed pairing induces short-lasting early-phase LTP.
      Heterosynaptically induced early-phase LTP could be depotentiated by repeatedly
      presenting unpaired test stimuli, whereas L-LTP could not. This
      heterosynaptically induced L-LTP requires PKA and protein synthesis. In addition,
      heterosynaptically induced L-LTP is impaired in transgenic mice that express
      KCREB (a dominant negative inhibitor of adenosine 3'5'-cyclic monophosphate
      response element-binding protein-mediated transcription) in the hippocampus.
      These mice have previously been shown to be impaired in spatial memory but have
      normal L-LTP as induced by a conventional homosynaptic tetanic protocol. These
      data suggest that at least in some instances this L-LTP-inducing protocol may
      better model behaviorally relevant information storage and the in vivo mechanisms
      underlying long-lasting memories.

PMID- 14711996
TI  - Glucocorticoid effects on object recognition memory require training-associated
      emotional arousal.
AB  - Considerable evidence implicates glucocorticoid hormones in the regulation of
      memory consolidation and memory retrieval. The present experiments investigated
      whether the influence of these hormones on memory depends on the level of
      emotional arousal induced by the training experience. We investigated this issue
      in male Sprague-Dawley rats by examining the effects of immediate posttraining
      systemic injections of the glucocorticoid corticosterone on object recognition
      memory under two conditions that differed in their training-associated emotional
      arousal. In rats that were not previously habituated to the experimental context,
      corticosterone (0.3, 1.0, or 3.0 mg/kg, s.c.) administered immediately after a 3
      min training trial enhanced 24-hr retention performance in an inverted-U shaped
      dose-response relationship. In contrast, corticosterone did not affect 24-hr
      retention of rats that received extensive prior habituation to the experimental
      context and, thus, had decreased novelty-induced emotional arousal during
      training. Additionally, immediate posttraining administration of corticosterone
      to nonhabituated rats, in doses that enhanced 24-hr retention, impaired object
      recognition performance at a 1-hr retention interval whereas corticosterone
      administered after training to well-habituated rats did not impair 1-hr
      retention. Thus, the present findings suggest that training-induced emotional
      arousal may be essential for glucocorticoid effects on object recognition memory.

PMID- 14711998
TI  - PLASTOCHRON1, a timekeeper of leaf initiation in rice, encodes cytochrome P450.
AB  - During postembryonic development of higher plants, the shoot apical meristem
      produces lateral organs in a regular spacing (phyllotaxy) and a regular timing
      (plastochron). Molecular analysis of mutants associated with phyllotaxy and
      plastochron would greatly increase understanding of the developmental mechanism
      of plant architecture because phyllotaxy and plastochron are fundamental
      regulators of plant architecture. pla1 of rice is not only a plastochron mutant
      showing rapid leaf initiation without affecting phyllotaxy, but also a
      heterochronic mutant showing ectopic shoot formation in the reproductive phase.
      Thus, pla1 provides a tool for analyzing the molecular basis of temporal
      regulation in leaf development. In this work, we isolated the PLA1 gene by map
      based cloning. The identified PLA1 gene encodes a cytochrome P450, CYP78A11,
      which potentially catalyzes substances controlling plant development. PLA1 is
      expressed in developing leaf primordia, bracts of the panicle, and elongating
      internodes, but not in the shoot apical meristem. The expression pattern and
      mutant phenotype suggest that the PLA1 gene acting in developing leaf primordia
      affects the timing of successive leaf initiation and the termination of
      vegetative growth.

PMID- 14711999
TI  - Managing the open abdomen.
AB  - Control of intra-abdominal fluid secretion, facilitation of abdominal
      exploration, and preservation of the fascia for abdominal wall closure is a major
      challenge in the management of patients with an open abdomen. Studies comparing
      different protocols of care have not been conducted and frequency of exploration,
      surgical procedures, and indications for definitive closure are generally based
      on clinical judgment. Morbidity and mortality rates are high. Vacuum-assisted
      therapy has been reported to help meet the challenges of managing the open
      abdomen and is particularly useful in patients with abdominal compartment
      syndromes, traumatic injuries, and severe intra-abdominal sepsis. Over the years,
      clinicians have developed various approaches to achieve vacuum-assisted closure
      using wall suction. Some disadvantages of the wall-suction methods are eliminated
      when using more recently developed vacuum therapy devices. These devices apply
      subatmospheric pressure, reducing bowel edema, bacterial counts, and inflammatory
      substances found in open abdominal wounds while eliminating the need for frequent
      dressing changes, maintaining intact skin, and improving fluid management. The
      results of six case studies presented are encouraging, suggesting that this
      treatment approach is safe and effective. Controlled clinical studies to
      establish the safety and effectiveness of this treatment approach and to
      facilitate the development of treatment guidelines are needed to help manage an
      increasingly common group of patients who might benefit from this treatment
      approach.

PMID- 14712000
TI  - The law on failure to treat pain.

PMID- 14712001
TI  - Small details make a difference: tail closures.

PMID- 14712002
TI  - A long-term view of long-term care.

PMID- 14712003
TI  - Illness behavior and social support in patients with chronic venous ulcers.
AB  - Venous ulcers are a chronic and costly condition for providers and payors, as
      well as for patients, particularly the elderly. To examine the association
      between chronic venous ulceration, illness behavior, and levels of social
      support, patients drawn from a separate clinical trial (N = 74) were interviewed
      using the Illness Behaviour Questionnaire and the Social Support Questionnaire.
      Results indicate that women had higher hypochondriasis (1.70 versus 1.03, P =
      0.19), affective disturbance (2.70 versus 1.42, P = 0.08), and number of supports
      (Social Support Questionnaire, 2.41 versus 1.81, P = 0.056) than men, although no
      score achieved a standard level of statistical significance. Patients under 70
      years of age had significantly higher hypochondriasis (1.96 versus 1.17, P =
      0.021) and irritability (1.38 versus 0.90, P = 0.026) scores than those older
      than 70 years, although denial was significantly higher in those older than 70
      years (3.97 versus 3.46, P = 0.045). The level of satisfaction with social
      support was significantly higher in those under 70 years of age (5.13 versus
      4.97, P = 0.042). These results underscore the psychological and social cost
      imposed by chronic venous ulceration on older women. They also support previous
      studies implying a greater psychological burden on younger patients. The
      association between illness behavior and social support remains unclear, but
      examining the association between illness behavior and social support among
      patients with venous ulceration provides an opportunity to increase understanding
      of the psychological, physical, and social dynamics of this chronic condition.

PMID- 14712004
TI  - Understanding venous leg ulcer pain: results of a longitudinal study.
AB  - Venous leg ulcer pain experienced during compression bandaging is poorly
      understood. A prospective, pilot cohort study was initiated to determine the
      feasibility of conducting a large-scale, repeated measures cohort study of venous
      leg ulcer pain and to document and describe the venous leg ulcer pain experience
      during the first 5 weeks of treatment with compression bandages. Eligible
      individuals admitted to a nurse-led community leg ulcer service in one Canadian
      community were recruited for the 5-week study. Pain assessment tools (ie,
      numerical rating scale and short form McGill Pain Questionnaire) were evaluated
      by 20 venous ulcer patients (mean age = 73.7 years) and their nurses for ease of
      use during one baseline and five weekly follow-up visits. Health-related quality
      of life (HRQL) information was obtained. Nurses reported on ease of integrating
      pain data collection into regular clinical care. Each pain assessment tool was
      audited for completion. Most participants found the pain assessment tools easy to
      use, but nurses reported lengthened visit times with some participants as a
      result of tool administration difficulties, particularly the visual analogue
      scale (VAS). Overall completeness of pain assessment tools ranged from 85.0%
      (visual analogue scale) to 96.3% (present pain intensity and word descriptor
      list). The vast majority of patients (18) reported ulcer pain at baseline. Total
      mean scores for all pain assessment tools used decreased over time, but most
      patients reported pain throughout the study. The most common pain descriptors
      used were "aching," "stabbing," "sharp," "tender," and "tiring." Health-related
      quality of life was low and did not change during the 5-week study. The results
      of this study suggest that the vast majority of venous ulcer patients experience
      pain and that it is feasible to examine this pain in individuals receiving care
      in the community over time.

PMID- 14712005
TI  - Venous leg ulcer patient priorities and quality of care: results of a survey.
AB  - A comprehensive patient evaluation of quality of care encompasses assessment and
      patient-rated prioritization of the various provisions of care. One hundred
      consecutive venous leg ulcer patients treated in a multidisciplinary wound
      healing center were invited to participate in a cross-sectional study to assess
      the quality of and assign priority to 28 aspects of medical technical,
      interpersonal, and organizational care. The response rate to the mailed
      questionnaire and follow-up telephone survey was 80%. Almost half (46%) of
      patients (median age 76 years, range 30 to 92) had an ulcer history of >5 years.
      Seventy-three patients (91%) were satisfied with the overall quality of care. A
      linear relationship was observed between average assessment score and the
      relative importance of the quality aspects studied. The quality of medical
      technical care and empathy aspects of interpersonal care received the most
      positive assessments and were given highest priority. Next in importance were the
      quality and coherence of information provided and cooperation between different
      healthcare sectors. Organizational aspects of care were less positively assessed
      and received lower priority ratings. Venous leg ulcer care, as provided in a
      multidisciplinary wound healing center, was assessed as satisfactory by patients,
      but areas for improvement - notably, cooperation between healthcare sectors and
      continuity of care - were observed.

PMID- 14712006
TI  - Using role models in ostomy rehabilitation.

PMID- 14712007
TI  - The anatomy of incontinence--what practitioners and patients need to know.
AB  - Stress urinary incontinence, a common problem for many women, is caused by
      hypermobility of the urethra and sphincteric deficiency. Vaginal detachments
      result in urethral hypermobility and vaginal prolapse. The focus for most
      clinicians has been solely on the urethra as the contributing factor to stress
      incontinence. However, to ensure success of continence surgery, a frequently used
      treatment with many procedural options, a concerted effort must be made to
      evaluate the global health of the vagina, treat all existing defects, and
      recreate normal pelvic support anatomy. The anatomy of urinary incontinence, the
      history of surgical procedures, as well as the advantages and disadvantages of
      current surgical techniques are described.

PMID- 14712008
TI  - Identifying and treating reversible causes of urinary incontinence.
AB  - Urinary incontinence can be a symptom of a variety of reversible conditions.
      Common and reversible causes of urinary incontinence include polyuria, exposure
      to irritants (including concentrated urine), infection, urinary retention, use of
      pharmaceuticals, stool impaction or constipation, atrophic urethritis or
      vaginitis, restricted mobility or dexterity, psychological conditions, and
      delirium or acute confused state. Healthcare professionals can use existing
      assessment strategies, tools, and parameters to guide decisions and treatment
      options to manage these conditions. First-line assessment tools are reviewed,
      including the use of a voiding and bowel diary, simple dipstick urinalysis,
      catheterization for post-void residual, the Folstein Mini Mental Status
      evaluation, and the Geriatric Depression Scale. Guidelines for estimating normal
      ranges of urine output, the influence of irritants, the risk of incontinence
      caused by stool impaction, and urinary retention are discussed. Primary care
      providers are well positioned to rule out or treat many of the reversible causes
      of urinary incontinence using simple assessment tools and pragmatic guidelines.

PMID- 14712009
TI  - Indwelling catheter management: from habit-based to evidence-based practice.
AB  - Indwelling urinary catheters are used in the care of more than five million
      patients per year. Prevalence rates range from 4% in home care to 25% in acute
      care. Catheter-associated urinary tract infections account for more than 40% of
      all nosocomial infections and can be associated with significant complications.
      Clinical practices in catheter management vary widely and frequently are not
      evidence-based. Effective nursing measures include: identifying patients who no
      longer need indwelling catheters, discussing appropriate catheter alternatives,
      and providing patient and caregiver education. Many catheter-associated problems
      can be avoided by selecting a closed catheter system with a small size catheter
      (14 to 18 French with a 5-cc balloon), following manufacturer's recommendations
      for inflation/deflation, maintaining a closed system, securing the catheter, and
      properly positioning the drainage bag. Practices such as routine catheter
      irrigation should be avoided. Current recommendations related to the management
      of encrustation and blockage also are discussed. Providing evidence-based
      catheter management strategies may reduce the rate of catheter-associated urinary
      tract infection, catheter encrustation, and leakage as well as the discomfort and
      costs associated with these complications.

PMID- 14712010
TI  - Promoting continence: simple strategies with major impact.
AB  - Urinary incontinence is a common problem, especially among women, yet it remains
      underreported and undertreated. This is partly due to patients' beliefs that
      little can be done and partly due to healthcare professionals' perception that
      treatment is limited to surgery, advanced behavioral strategies requiring
      specialized equipment, or containment devices. Nurses are in a strategic position
      to reduce the incidence of incontinence by teaching bladder health strategies
      (ie, fluid management, appropriate voiding intervals, constipation prevention,
      weight control, smoking cessation, and pelvic muscle exercises), actively
      assessing patients for incontinence, and initiating appropriate referrals and
      primary interventions. Patients with significant neurologic deficits, structural
      abnormalities such as pelvic organ prolapse, or urinary retention should be
      referred for further workup. However, most patients can be treated with primary
      continence restoration strategies, which include identifying and correcting
      reversible factors such as urinary tract infection or atrophic urethritis;
      instruction in pelvic floor muscle exercises; and instruction regarding urge
      inhibition strategies. Implementing these simple strategies can significantly
      improve bladder function and continence in the majority of patients.

PMID- 14712014
TI  - Lead bismuth calcium sodium phosphate: Pb4.6Bi0.4Ca2.6Na2.4(PO4)6.
AB  - The title compound, lead bismuth calcium sodium phosphate,
      Pb(4.6)Bi(0.4)Ca(2.6)Na(2.4)(PO(4))(6) crystallizes in the apatite structure
      type, with vacancies in sites 2a or 2b that are normally occupied by anions. The
      fact that the Bi and Pb ions are mainly localized in the 6h sites confirms the
      electron lone-pair influence on the apatite structure.

PMID- 14712015
TI  - (NH4)4Cd(HSeIVO3)2(SeVIO4)2: a new structure type with krohnkite-like chains.
AB  - Tetraammonium cadmium dihydrogenselenite(IV) diselenate(VI),
      (NH(4))(4)Cd(HSe(IV)O(3))(2)(Se(VI)O(4))(2), is the third example of a compound
      containing both hydrogen selenite and selenate anions, and has a new structure
      type. It contains krohnkite-like heteropolyhedral chains in which CdO(6)
      octahedra are linked via bridging HSeO(3) groups, having their remaining two
      trans apices decorated by SeO(4) groups. The charge-balancing NH(4) groups are
      involved in weak hydrogen bonding, whereas the H atom of the HSeO(3) group
      provides a strong hydrogen bond [O...O = 2.614 (5) A]. The average Cd-O bond
      length is 2.298 A. All atoms are on general positions except Cd (on -1).
      Relations to the krohnkite-type compounds Na(2)Mg(SO(3)).2H(2)O,
      Ba(2)CoCl(2)(SeO(3))(2) and Ba(2)Ca(HPO(4))(2)(H(2)PO(4))(2), and to the mineral
      curetonite are discussed. Unit-cell data are given for an isotypic Mn(II)
      analogue.

PMID- 14712016
TI  - Uranium cobalt tetraaluminide, UCoAl4.
AB  - The structure of UCoAl(4) can be viewed as a succession of atomic layers, with
      the compositions UCoAl and Al(3), that alternate along the c axis. The packing
      within the pure Al layer at z = 1/2 results from edge-sharing of triangles,
      squares and pentagons of Al atoms. Two successive Al(3) layers thus define
      pentagonal, square-based and trigonal prisms which are centred at z = 0 by the U,
      Co and remaining Al atoms. UCoAl(4) is a high-temperature phase that is only
      observed in as-cast samples.

PMID- 14712017
TI  - Dipotassium aquapentafluorovanadate.
AB  - The title compound, K(2)[VF(5)(H(2)O)], was synthesized from potassium antimony
      tartrate, piperazine, V(2)O(5) and HF under hydrothermal conditions. It is
      isostructural with K(2)[FeF(5)(H(2)O)] and contains polymeric anion chains held
      together by strong O-H...F bonds. Each V atom is coordinated to five terminal F
      atoms and the O atom of one water molecule. Pairs of O-H...F bonds are formed by
      two cis-related F atoms. Twofold axes run along the O-V-F axis of the V-centred
      otahedra.

PMID- 14712018
TI  - Di-mu-hydroxo-bis([bis[2-(2-pyridyl)ethyl]amine-kappa 3N]copper(II)) dichloride
      hexahydrate.
AB  - The title compound, [Cu(2)(OH)(2)(C(14)H(17)N(3))(2)]Cl(2).6H(2)O, is a
      crystallographically centrosymmetric dimer of square-pyramidal Cu(II) centres,
      with a basal-basal [Cu(2)(mu-OH)(2)](2+) bridging motif and apical pyridyl
      donors. The Cl(-) anion is hydrogen bonded to one O-H and one N-H group, and to
      three different water molecules. Because of disorder, the network of
      intramolecular hydrogen bonding in the hydrated lattice is only partly resolved.

PMID- 14712019
TI  - Trans-dichloro-cis-bis(3,6-dimethylcarbazolyl)-cis
      bis(tetrahydrofuran)zirconium(IV) benzene sesquisolvate.
AB  - In the title compound, [ZrCl(2)(C(14)H(12)N)(2)(C(4)H(8)O)(2)].1.5C(6)H(6), the
      Zr atom is pseudo-octahedral, with two Cl atoms in trans positions and two
      tetrahydrofuran molecules in cis positions. The two 3,6-dimethylcarbazolyl
      ligands are in cis positions and are canted with respect to one another. The two
      Zr-N distances are 2.1148 (18) and 2.1236 (18) A, and the N-Zr-N angle is 95.08
      (7)degrees. The title compound crystallizes as the benzene solvate, with one of
      the benzene molecules positioned on an inversion center.

PMID- 14712020
TI  - Trans-dichloro(dimethyl sulfide-kappa S)(pyridine-kappa N)platinum(II).
AB  - The structure of the title compound, [PtCl(2)(C(5)H(5)N)(C(2)H(6)S)], consists of
      discrete molecules in which the Pt-atom coordination is slightly distorted square
      planar. The Cl atoms are trans to each other, with a Cl-Pt-Cl angle of 176.60 (7)
      degrees. The pyridine ligand is rotated 64.5 (2) degrees from the Pt square plane
      and one of the Pt-Cl bonds essentially bisects the C-S-C angle of the dimethyl
      sulfide ligand. In the crystal structure, there are extensive weak C-H...Cl
      interactions, the shortest of which connects molecules into centrosymmetric
      dimers. A comparison of the structural trans influence on Pt-S and Pt-N distances
      for PtS(CH(3))(2) and Pt(pyridine) fragments, respectively, in square-planar
      Pt(II) complexes is presented.

PMID- 14712021
TI  - Potassium carbamoyldicyanomethanide.
AB  - The crystal structure of the title compound, K[(CN)(2)CC(O)NH(2))] or
      K(+).C(4)H(2)N(3)O(-), conventionally abbreviated as Kcdm, where cdm is
      carbamoyldicyanomethanide, is described. The bond lengths and angles of the cdm
      cation are comparable to those reported previously for
      [M(cdm)(2)(H(2)O)(4)].2H(2)O (M = Ni, Mn and Co). The K atoms are coordinated to
      four nitrile N atoms and two carbonyl O atoms in a distorted trigonal prismatic
      fashion, with two further N atoms semicoordinated through the centers of two
      prism side faces. This coordination leads to the formation of mixed anion-cation
      sheets parallel to the ab plane, which are joined together via hydrogen-bonding
      interactions. The cdm anion is potentially useful for the formation of transition
      metal coordination polymers, in which magnetic superexchange could occur through
      a bidentate cdm bridge. Kcdm provides a model compound by which the molecular
      geometry of the cdm anion can be analyzed.

PMID- 14712022
TI  - AgI and CuI binuclear macrocyclic complexes with 1-(3-pyridyl)ethanone oxime.
AB  - Bis[micro-1-(3-pyridyl)ethanone oxime-kappa(2)N:N']bis[nitratosilver(I)],
      [Ag(2)(NO(3))(2)(C(7)H(8)N(2)O)(2)], crystallizes as a centrosymmetric binuclear
      macrocylic complex containing silver(I) ions bridged by the organic 1-(3
      pyridyl)ethanone oxime ligand. The ligand coordinates via the pyridine and the
      oxime N atoms. A similar metal-ligand arrangement was found in the copper(I)
      complex catena-poly[[bis[micro-1-(3-pyridyl)ethanone oxime
      kappa(2)N:N']dicopper(I)]-di-micro-iodo], [Cu(2)I(2)(C(7)H(8)N(2)O)(2)](n), but
      here the centrosymmetric macrocycles are connected by double anion bridges,
      resulting in the formation of a one-dimensional coordination polymer.

PMID- 14712023
TI  - Catena-poly[bis[aqua(2,2-bipyridine-kappa 2N,N')cobalt(II)]-mu-1,2,4,5
      benzenetetracarboxylato-kappa 4O1:O2:O3:O4].
AB  - In the title complex, [Co(2)(C(10)H(2)O(8))(C(10)H(8)N(2))(2)(H(2)O)(2)], the
      four carboxylate groups are fully deprotonated and coordinate to four Co(II)
      cations in a monodentate fashion, forming a one-dimensional ribbon-like double
      chain structure, with centrosymmetric
      [Co(2)(C(10)H(2)O(8))(C(10)H(8)N(2))(2)(H(2)O)(2)] repeating units and a cavity
      of approximately 6.8 x 6.6 A. Moreover, a three-dimensional supramolecular
      structure is formed by face-to-face pi-pi interactions between the aromatic rings
      of the 2,2'-bipyridine moieties of two adjacent chains, and by hydrogen-bonding
      interactions between the coordinated aqua O atom and the coordinated carboxyl O
      atom from different chains.

PMID- 14712024
TI  - Cocrystal of the [MnIVC2H7N5)3]4+ ion and biguanidium: a double hydrogen-bond
      interaction with guanidinium-recognizing anions.
AB  - Biguanidium tris(biguanide-kappa(2)N(2),N(4))manganese(IV) hexanitrate,
      (C(2)H(9)N(5))[Mn(C(2)H(7)N(5))(3)](NO(3))(6), is a cocrystal of the
      [Mn(IV)(C(2)H(7)N(5))(3)](4+) ion and biguanidium. The cocrystal exhibits a
      double hydrogen-bonding interaction between the biguanide and nitrate groups,
      which is rarely observed in crystal structures but is proposed as a recognition
      mode for guanidinium-recognizing anionic groups in biological systems. In this
      cocrystal structure, biguanide moieties exist both as divalent cations and as
      neutral molecules.

PMID- 14712025
TI  - Chloro(L-glutamato-kappa 2N,O)(1,10-phenanthroline-kappa 2,N')copper(II)
      monohydrate.
AB  - The crystal structure of the title compound,
      [CuCl(C(5)H(8)NO(4))(C(12)H(8)N(2))].H(2)O or [CuCl(L-Glu)(phen)].H(2)O (where
      phen is 1,10-phenanthroline and L-Glu is L-glutamate), shows that the ternary
      complex consists of two neutral molecules, in which the Cu(II) ions each have a
      distorted square-pyramidal coordination geometry comprised of one bidentate
      phenanthroline ligand, one O,N-bidentate L-glutamate anion and an apical Cl(-)
      anion. The angles between the planes of the Cu-phenanthroline and the Cu
      aminocarboxylate chelate rings are 6.1 (5) and 11.8 (5) degrees in the two
      molecules. The Cu-Cl bond lengths are 2.608 (3) and 2.590 (3) A in the two
      molecules, slightly longer than the value of 2.546 A observed for the Cu-Cl bond
      in the analogous chloro(L-glycinato)(1,10-phenanthroline)copper complex [Solans,
      Ruiz-Ramirez, Martinez, Gasque & Brianso (1983). Acta Cryst. C44, 628-631].
      Additionally, the Cu ion is weakly coordinated at a sixth position by an alpha
      carboxyl O atom from a neighbouring complex. A number of intra- and
      intermolecular hydrogen bonds stabilize the crystal structure.

PMID- 14712026
TI  - Bis[aminoguanidinium(1+)] hexafluorozirconate(IV): redeterminations and normal
      probability analysis.
AB  - The crystal structure of bis[aminoguanidinium(1+)] hexafluorozirconate(IV),
      (CH(7)N(4))(2)[ZrF(6)], originally reported by Bukvetskii, Gerasimenko &
      Davidovich [Koord. Khim. (1990), 16, 1479-1484], has been redetermined
      independently using two different samples. Normal probability analysis confirms
      the reliability of all refined parameter standard uncertainties in the new
      determinations, whereas systematic error detectable in the earlier work leads to
      a maximum difference of 0.069 (6) A in atomic positions between the previously
      reported and present values of an F-atom y coordinate. Radiation-induced
      structural damage in aminoguanidinium polyfluorozirconates may result from minor
      displacements of H atoms in weak N-H...F bonds to new potential minima and
      subsequent anionic realignment.

PMID- 14712027
TI  - Bis[bis[5-tert-butyl-2-oxido-3-(1-pyridiniomethyl)phenyl]methane]dioxouranium
      bis(trifluoromethanesulfonate) pyridine disolvate: a uranyl bis(diphenoxide)
      complex resulting from homooxacalixarenecleavage.
AB  - The title compound, [UO(2)(C(33)H(38)N(2)O(2))(2)](CF(3)SO(3))(2).2C(5)H(5)N, has
      been obtained by reaction of U(IV) trifluoromethanesulfonate with p-tert
      butyltetrahomodioxacalix[4]arene in pyridine. The uranyl ion lies on an inversion
      centre and is bound to two O atoms from each diphenoxide ligand, which gives the
      usual square-planar equatorial environment. The zwitterionic diphenoxide species
      results from nucleophilic attack by pyridine on the benzylic ether C atoms of the
      homooxacalixarene, assisted by initial U coordination to the ether groups, with
      subsequent metal oxidation giving the uranyl moiety.

PMID- 14712028
TI  - Mer-(4-aminobenzenesulfonato-kappa N)triaqua(1,10-phenanthroline-kappa
      2N,N')cobalt(II) chloride.
AB  - Both coordination and hydrogen bonds contribute to networking in the
      supramolecular title compound, [Co(C(6)H(6)NO(3)S)(C(12)H(8)N(2))(H(2)O)(3)]Cl,
      which contains a discrete [Co(C(6)H(6)NO(3)S)(C(12)H(8)N(2))(H(2)O)(3)](+)
      complex cation, formed by one 4-aminobenzenesulfonate ligand, one 1,10
      phenanthroline ligand and three coordinated water molecules, together with one
      uncoordinated chloride anion. These discrete cations and chloride anions are
      connected by hydrogen-bonding interactions into a two-dimensional supramolecular
      motif. Further hydrogen-bonding interactions consolidate the structural
      architecture and extend the two-dimensional supramolecular structure into a three
      dimensional network.

PMID- 14712029
TI  - Tetrakis(tetramethylammonium) dodeca-mu-chloro-hexachloro-octahedro-hexatantalate
      chloride.
AB  - The title compound, (C(4)H(12)N)(4)[Ta(6)Cl(18)]Cl, crystallizes in the cubic
      space group Fm-3m. The crystal structure contains two different types of
      coordination polyhedra, i.e. four tetrahedral [(CH(3))(4)N](+) cations and one
      octahedral [(Ta(6)Cl(12))Cl(6)](3-) cluster anion, and one Cl(-) ion. The
      presence of three different kinds of Cl atoms [bridging (mu(2)), terminal and
      counter-anion] in one molecule makes this substance unique in the chemistry of
      hexanuclear halide clusters of niobium and tantalum. The Ta(6) octahedron has an
      ideal O(h) symmetry, with a Ta-Ta interatomic distance of 2.9215 (7) A.

PMID- 14712030
TI  - Bis(saccharinato-kappa N)zinc(II) complexes with N,N'-bidentate 2
      aminomethylpyridine and 2-aminoethylpyridine.
AB  - The structures of trans-bis[2-(aminomethyl)pyridine-kappa(2)N,N']bis(saccharinato
      kappa N)zinc(II), [Zn(C(7)H(4)NO(3)S)(2)(C(6)H(8)N(2))(2)], (I), and [2
      (aminoethyl)pyridine-kappa(2)N,N']bis(saccharinato-kappa N)zinc(II),
      [Zn(C(7)H(4)NO(3)S)(2)(C(7)H(10)N(2))], (II), exhibit octa- and tetrahedrally
      coordinated Zn(II) atoms, respectively. The diamine ligands behave as N,N'
      bidentate ligands, while saccharinate (sac) is coordinated through the N atom. In
      (I), the complex lies about an inversion centre with the Zn atom disordered and
      displaced by 0.256 (2) A from a centre of symmetry towards a sac N atom. The
      crystal structure of (I) is stabilized by N-H...O hydrogen bonds and the crystal
      packing of (II) is determined by hydrogen bonding as well as weak pi-pi stacking
      interactions between the sac ligands.

PMID- 14712031
TI  - Four trifluoromethylnitrobenzene analogues.
AB  - The crystal structures of four trifluoromethylnitrobenzene analogues
      (CF(3))C(6)H(3)(NO(2))[C(4)H(8)N(2)]R (where C(4)H(8)N(2) is piperazinyl and R is
      ethyl carboxylate, CO(2)C(2)H(5), or phenyl, C(6)H(5)), have been determined, and
      their conformations and packing arrangements are compared. The four compounds are
      ethyl 4-[4-nitro-2-(trifluoromethyl)phenyl]piperazine-1-carboxylate, (I), and
      ethyl 4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine-1-carboxylate, (II), both
      C(14)H(16)F(3)N(3)O(4), and 1-[4-nitro-2-(trifluoromethyl)phenyl]-4
      phenylpiperazine, (III), and 1-[2-nitro-4-(trifluoromethyl)phenyl]-4
      phenylpiperazine, (IV), both C(17)H(16)F(3)N(3)O(2). All molecules adopt a rod
      like conformation, while the asymmetric units of (II) and (IV) contain two unique
      molecules that pack as monodirectional pairs. All molecules pack with C-H...O/F
      close contacts to all but one of the O atoms and to five of the 18 F atoms.

PMID- 14712032
TI  - (Z)-2-(1H-Indol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-one.
AB  - The title compound, C(16)H(16)N(2)O, which contains a double bond connecting an
      azabicyclic ring system to an indol-3-ylmethylene group, crystallizes from a
      solution in ethyl acetate. The geometries of the two crystallographically
      independent molecules are nearly identical. The crystal packing of the title
      compound involves two types of intermolecular hydrogen bond.

PMID- 14712033
TI  - Two isomers of 2,4-dibenzyl-8-azabicyclo[3.2.1]octan-3-ol.
AB  - The crystal structures of the title compounds, 2 alpha,4 alpha-dibenzyl-3 alpha
      tropanol (2 alpha,4 alpha-dibenzyl-8-methyl-8-azabicyclo[3.2.1]octan-3 alpha-ol),
      C(22)H(27)NO, (I), and 2 alpha,4 alpha-dibenzyl-3 beta-tropanol (2 alpha,4 alpha
      dibenzyl-8-methyl-8-azabicyclo[3.2.1]octan-3 beta-ol), C(22)H(27)NO, (II), show
      that both compounds have a piperidine ring in a chair conformation and a
      pyrrolidine ring in an envelope conformation. Isomer (I) is asymmetric, the
      benzyl groups having different orientations, whereas isomer (II) is mirror
      symmetric, and the N and O atoms, the C atom attached to the hydroxy group, and
      the methyl C atom attached to the N atom lie on the mirror plane. In the crystal
      structures of both (I) and (II), the molecules are linked together by
      intermolecular O-H...N hydrogen bonds to form chains that run parallel to the a
      direction in (I) and parallel to b in (II).

PMID- 14712034
TI  - Three-dimensional aggregation in 2-hydroxy-3-iodo-5-nitrobenzaldehyde involving C
      H...O, iodo-nitro and aromatic pi-pi stacking interactions, and isolated dimers
      in disordered 2,4-diiodo-6-nitroanisole.
AB  - In 2-hydroxy-3-iodo-5-nitrobenzaldehyde, C(7)H(4)INO(4), the molecules are linked
      into sheets by a combination of C-H.O hydrogen bonds and two-centre iodo-nitro
      interactions, and these sheets are linked by aromatic pi-pi stacking
      interactions. Molecules of 2,4-diiodo-6-nitroanisole, C(7)H(5)I(2)NO(3), are
      disordered, with the nitro group and one of the I substituents each occupying
      common sets of sites with 0.5 occupancy. The molecules are linked into isolated
      centrosymmetric dimeric units by a single iodo-nitro interaction.

PMID- 14712035
TI  - 2-Amino-5-nitrothiazole monoethanol solvate: triply-interwoven hydrogen-bonded
      sheets containing centrosymmetric R2 2(8) and RR10 10(38) rings.
AB  - 2-Amino-5-nitrothiazole crystallizes from solution in ethanol as a monosolvate,
      C(3)H(3)N(3)O(2)S.C(2)H(6)O, in which the thiazole component has a strongly
      polarized molecular-electronic structure. The thiazole molecules are linked into
      centrosymmetric dimers by paired N-H...N hydrogen bonds [H...N = 2.09 A, N.N =
      2.960 (6) A and N-H...N = 169 degrees ], and these dimers are linked by the
      ethanol molecules, via a two-centred N-H...O hydrogen bond [H...O = 1.98 A, N...O
      = 2.838 (5) A and N-H...O = 164 degrees ] and a planar asymmetric three-centred O
      H...(O)(2) hydrogen bond [H...O = 2.07 and 2.53 A, O...O = 2.900 (5) and 3.188
      (5) A, O-H...O = 169 and 136 degrees, and O...H...O = 55 degrees ], into sheets
      built from alternating R(2)(2)(8) and R(10)(10)(38) rings. These sheets are
      triply interwoven.

PMID- 14712036
TI  - Hydrogen-bonded chains of rings in 3-iodobenzaldehyde 2,4-dinitrophenylhydrazone
      and 4-iodobenzaldehyde 2,4-dinitrophenylhydrazone, and a three-dimensional
      framework in 4-iodobenzaldehyde 4-nitrophenylhydrazone generated by the
      combination of N-H...O and C-H...O hydrogen bonds with iodo-nitro interactions.
AB  - Molecules of 3- and 4-iodobenzaldehyde 2,4-dinitrophenylhydrazone,
      C(13)H(9)IN(4)O(4), are both effectively planar. In the crystal structure of each
      compound, molecules are linked by a combination of N-H...O and C-H...O hydrogen
      bonds into complex chains of rings, containing four and three different ring
      motifs, respectively; neither compound contains any iodo-nitro interactions. In 3
      iodobenzaldehyde 4-nitrophenylhydrazone, C(13)H(10)IN(3)O(2), where the iodinated
      aryl ring is disordered over two sets of sites, the hydrogen bonds generate a
      chain of rings, while two independent I...O interactions generate a three
      dimensional framework.

PMID- 14712037
TI  - A three-dimensional hydrogen-bonded framework in N-(3-nitrophenyl)phthalimide,
      and hydrogen-bonded chains of rings in N-(3,5-dinitrophenyl)phthalimide, linked
      into sheets by dipolar interactions.
AB  - Molecules of N-(3-nitrophenyl)phthalimide, C(14)H(8)N(2)O(4), are linked into a
      three-dimensional framework by four distinct C-H...O hydrogen bonds [H...O = 2.35
      2.58 A, C.O = 3.105 (5)-3.432 (5) A and C-H...O = 128-167 degrees ]. Molecules of
      N-(3,5-dinitrophenyl)phthalimide, C(14)H(7)N(3)O(6), lie across twofold rotation
      axes in space group P2/n and are linked by a single C-H...O hydrogen bond [H...O
      = 2.58 A, C...O = 3.410 (2) A and C-H..O = 147 degrees ] into chains of rings.
      These chains are weakly linked into sheets by intermolecular interactions
      involving short dipolar O...N and O...C contacts.

PMID- 14712038
TI  - Three N2-benzoyloxybenzamidines: sheet structures built from hard and soft
      hydrogen bonds and aromatic pi-pi stacking interactions.
AB  - Molecules of the title compounds N(2)-(benzoyloxy)benzamidine,
      C(14)H(12)N(2)O(2), (I), N(2)-(2-hydroxybenzoyloxy)benzamidine,
      C(14)H(12)N(2)O(3), (II), and N(2)-benzoyloxy-2-hydroxybenzamidine,
      C(14)H(12)N(2)O(3), (III), all have extended chain conformations, with the aryl
      groups remote from one another. In (I), the molecules are linked into chains by a
      single N-H...N hydrogen bond [H...N = 2.15 A, N...N = 3.029 (2) A and N-H...N =
      153 degrees ] and these chains are linked into sheets by means of aromatic pi-pi
      stacking interactions. There is one intramolecular O-H...O hydrogen bond in (II),
      and a combination of one three-centre N-H...(N,O) hydrogen bond [H...N = 2.46 A,
      H.O = 2.31 A, N...N = 3.190 (2) A, N...O = 3.146 (2) A, N-H...N = 138 degrees and
      N-H...O = 154 degrees ] and one two-centre C-H...O hydrogen bond [H.O = 2.46 A,
      C...O = 3.405 (2) A and C-H...O = 173 degrees ] links the molecules into sheets.
      In (III), an intramolecular O-H...N hydrogen bond and two N-H...O hydrogen bonds
      [H...O = 2.26 and 2.10 A, N...O = 2.975 (2) and 2.954 (2) A, and N-H...O = 138
      and 163 degrees ] link the molecules into sheets.

PMID- 14712039
TI  - Hydrogen bonding in nitroaniline analogues: 4-nitrobenzaldehyde hydrazone forms
      hydrogen-bonded sheets of R4 4(26) rings.
AB  - Molecules of the title compound, C(7)H(7)N(3)O(2), are linked by two N-H...O
      hydrogen bonds [H...O = 2.42 and 2.47 A, N...O = 3.191 (4) and 3.245 (4) A, and N
      H...O = 150 and 151 degrees ] into sheets built from a single type of R(4)(4)(26)
      ring.

PMID- 14712040
TI  - Hydrogen bonding in C-substituted nitroanilines: pi-stacked sheets of R4 4(20)
      and R4 4(28) rings in 2-cyano-4-nitroaniline.
AB  - In the title compound, C(7)H(5)N(3)O(2), which crystallizes with Z' = 2 in space
      group P2(1)/c, the two independent molecules both exhibit positional disorder,
      with refined site-occupancy factors of 0.947 (2) and 0.053 (2) for the major and
      minor components, respectively. The major components have polarized molecular
      electronic structures. The two major components are linked into sheets of
      alternating R(4)(4)(20) and R(4)(4)(28) rings by two N-H...O hydrogen bonds
      [H...O = 2.18 and 2.21 A, N...O = 3.022 (2) and 3.043 (2) A and N-H...O both 159
      degrees ] and two N-H...N hydrogen bonds [H...N = 2.14 and 2.17 A, N...N = 2.990
      (2) and 3.001 (2) A, and N-H...N = 162 and 158 degrees ]. The sheets are linked
      into a three-dimensional framework by a single aromatic pi-pi stacking
      interaction.

PMID- 14712041
TI  - (E,E)-1,4-Diethyl-1,4-diphenyl-2,3-diazabutadiene.
AB  - Molecules of the title compound [(E,E)-propiophenone azine], C(18)H(20)N(2), lie
      across centres of inversion in space group P2(1)/c. The conformations of similar
      simple azines are discussed in terms of the soft hydrogen bonds present in the
      structures.

PMID- 14712042
TI  - 2,4,6-Trimethylbenzamide.
AB  - The crystal structure of the title compound, C(10)H(13)NO, displays an infinite
      one-dimensional network composed of primary amide molecules connected by N
      H...O[double bond]C hydrogen bonds involving the anti NH amide H atoms, thus
      generating a C(4) motif. This network is additionally stabilized by a weak N
      H...pi interaction between the syn-oriented amide H atom and the aromatic ring of
      a neighbouring molecule. The distance between the H atom and the ring centroid is
      2.50 A. The amide group and the aryl moiety are nearly perpendicular, forming an
      intramolecular dihedral angle of 84.69 (6) degrees.

PMID- 14712043
TI  - Two hydrates of 6-methoxypurine.
AB  - 6-Methoxypurine crystallizes from N,N-methylformamide as the hemihydrate,
      C(6)H(6)N(4)O.0.5H(2)O, and from water as the trihydrate, C(6)H(6)N(4)O.3H(2)O.
      Both forms crystallize in the triclinic crystal system. Upon heating the
      trihydrate, molecules of water are liberated successively; the hemihydrate is
      formed at 383 K. In the hemihydrate, the H atom on the imidazole N atom is
      disordered between the two N atoms. The water molecule in the hemihydrate and the
      H atoms of a water molecule in the trihydrate are also disordered. In the
      hemihydrate, the organic moieties are connected by N-H...N hydrogen bonds, while
      they are connected via water molecules in the trihydrate.

PMID- 14712044
TI  - Two dimorphs of 5-methylsulfanyl-1H-tetrazole.
AB  - 5-Methylsulfanyl-1H-tetrazole, C(2)H(4)N(4)S, crystallizes in dimorphic forms;
      the alpha-form crystallizes at room temperature in the monoclinic crystal system,
      space group P2(1)/m, and the beta-form crystallizes by sublimation at 423 K in
      the orthorhombic crystal system, space group Pbcm. In both forms, the molecules
      occupy crystallographic mirror planes and are connected to one another via N
      H...N hydrogen bonds, the amino H atoms being disordered. The two forms differ
      from one another in their packing; there are polar layers in the alpha-form and
      non-polar layers in the beta-form.

PMID- 14712045
TI  - Inclusion compounds of 2,5-diphenylhydroquinone.
AB  - The crystal structures of three 1:2 inclusion compounds that consist of host
      molecule 2,5-diphenylhydroquinone (C(18)H(14)O(2)) and the guest molecules 2
      pyridone (C(5)H(5)NO), 1,3-diphenyl-2-propen-1-one (chalcone, C(15)H(12)O) and 1
      (4-methoxyphenyl)-3-phenyl-2-propen-1-one (4'-methoxychalcone, C(16)H(14)O(2))
      were determined in order to study the ability of guest molecules in inclusion
      compounds to undergo photoreaction. All of the crystals were found to be
      photoresistant. The three inclusion compounds crystallize in triclinic space
      group P1. In each case, the host/guest ratio is 1:2, with the host molecules
      occupying crystallographic centers of symmetry and the guest molecules occupying
      general positions. The guest molecules in each of the inclusion compounds are
      linked to the host molecules by hydrogen bonds. In the inclusion compound where
      the guest molecule is pyridone, the host molecule is disordered so that the
      hydroxy groups are distributed between two different sites, with occupancies of
      0.738 (3) and 0.262 (3). The pyridone molecules form dimers via N-H...O hydrogen
      bonds.

PMID- 14712046
TI  - Three-dimensional hydrogen-bonding supramolecular architecture of 2-(3-pyridinio)
      5-(3-pyridyl)-1,3,4-oxadiazole perchlorate.
AB  - In the crystal structure of the title compound, C(12)H(9)N(4)O(+).ClO(4)(-), the
      protonated cation adopts a cis-I conformation and approximately planar geometry.
      Each perchlorate anion acts as the acceptor of three C-H...O weak interactions,
      which, together with N-H...N and C-H...N hydrogen bonds between the protonated
      cations, extend this structure into a three-dimensional hydrogen-bonded network.

PMID- 14712047
TI  - Hydrogen-bonding patterns in two structural isomers of 3,6-bis(2-chlorophenyl)
      1,4-dihydro-1,2,4,5-tetrazine.
AB  - Two structural isomers, 3,6-bis(2-chlorophenyl)-1,4-dihydro-1,2,4,5-tetrazine,
      (I), and 3,5-bis(2-chlorophenyl)-4-amino-1H-1,2,4-triazole, (II), both
      C(14)H(10)Cl(2)N(4), form chain-like structures in the solid state, stabilized by
      N-H...N and N-H...Cl hydrogen bonds. A contribution from weak interactions to the
      strong hydrogen-bond network is observed in both structures. The secondary graph
      sets for intermolecular hydrogen bonds [R(2)(2)(11) for (I) and R(2)(2)(12) for
      (II)] indicate the similarity between the networks.

PMID- 14712048
TI  - 1,4-Diethynyl-2,5-dimethoxybenzene at ca 150 K.
AB  - The principal determinants of packing in crystals of the title compound,
      C(12)H(10)O(2), which has crystallographically imposed inversion symmetry, are
      interactions between the alkyne H atoms and the methoxy O atoms [H...O = 2.39 (1)
      A].

PMID- 14712049
TI  - N,N-dimethylanilinium 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2
      olate.
AB  - In the title compound, C(8)H(12)N(+).C(8)HN(4)O(2)(-), the anion and cation lie
      on a crystallographic mirror plane and form planar ribbons via N-H...O [N...O =
      2.933 (4) A, H...O = 2.01 A and N-H...O = 170 degrees] and N-H...N [N...N = 3.016
      (5) A, H...N = 2.15 A and N-H...N = 169 degrees] hydrogen bonds. The ribbons are
      further linked via weak C-H...O and C-H...N hydrogen bonds. In adjacent planes,
      anions lie opposite cations; pi-pi interactions (separation a/2 = 3.520 A) exist
      between the anions and the cations, and stacks are formed, running along the a
      axis. The cations are disordered over two interpenetrating sites, with
      occupancies of 0.833 (5) and 0.167 (5).

PMID- 14712050
TI  - 2-Chlorophenyl 3-nitrobenzenesulfonate and 2,4-dichlorophenyl 3
      nitrobenzenesulfonate: supramolecular aggregation through C-H...O, pi-pi and van
      der Waals interactions.
AB  - In 2-chlorophenyl 3-nitrobenzenesulfonate, C(12)H(8)ClNO(5)S, and 2,4
      dichlorophenyl 3-nitrobenzenesulfonate, C(12)H(7)Cl(2)NO(5)S, weak C-H...O
      interactions generate S(5), S(6) and R(2)(2)(7) rings. The supramolecular
      aggregation is completed by the presence of pi-pi interactions and intermolecular
      van der Waals short contacts.

PMID- 14712051
TI  - A new monoclinic polymorph of methyl p-aminobenzoate.
AB  - Single crystals of methyl-p-aminobenzoate (MAB), C(8)H(9)NO(2), were obtained
      during the synthesis of 4-amino-N'-(5-nitro-2-thienylmethylene)benzohydrazide. A
      P2(1)/c polymorph [a = 8.5969 (4) A, b = 5.6053 (2) A, c = 15.5397 (7) A and beta
      = 96.172 (2) degrees ] of MAB was found and the intra- and intermolecular
      geometries were compared with those of the previously known C2/c structure [a =
      16.242 (2) A, b = 8.113 (2) A, c = 12.724 (2) A and beta = 69.17 (1) degrees;
      Xianti (1983). Jiegou Huaxue, 2, 219-221].

PMID- 14712052
TI  - 17-Oxo-5 alpha-androst-6-en-3 beta-yl acetate.
AB  - In the title compound, C(21)H(30)O(3), a potential inhibitor of aromatase, all
      rings are fused trans. Rings A and C have chair conformations which are slightly
      flattened, whereas the conformation of ring B is close to a half-chair. Ring D
      has a 14 alpha-envelope conformation. The steroid nucleus has a small twist, as
      shown by the C19-C10...C13-C18 (steroid numbering) torsion angle of -6.9 (3)
      degrees. Ab initio calculations of the equilibrium geometry of the molecule
      reproduce this small twist, which appears to be due to the conformation of ring B
      rather than to packing effects.

PMID- 14712053
TI  - Two androst-5-ene derivatives: 16-[4-(3-chloropropoxy)-3-methoxybenzylidene]-17
      oxoandrost-5-en-3 beta-ol and 16-[3-methoxy-4-(2-pyrrolidin-1
      ylethoxy)benzylidene]-3 beta-pyrrolidinoandrost-5-en-17 beta-ol monohydrate.
AB  - In the steroidal nucleus of 16-[4-(3-chloropropoxy)-3-methoxybenzylidene]-17
      oxoandrost-5-en-3 beta-ol, C(30)H(29)ClO(4), (I), the outer two six-membered
      rings are in chair conformations, while the five-membered ring and the central
      six-membered ring of the steroidal nucleus adopt half-chair and envelope
      conformations, respectively. In 16-[3-methoxy-4-(2-pyrrolidin-1
      ylethoxy)benzylidene]-3 beta-pyrrolidinoandrost-5-en-17 beta-ol monohydrate,
      C(37)H(54)N(2)O(3).H(2)O, (II), one C atom of one of the outer six-membered rings
      of the steroid nucleus and the four C atoms of the ethoxypyrrolidine ring are
      disordered over two sites. The five-membered ring, and the central and one of the
      outer six-membered rings of the steroidal nucleus exhibit distorted half-chair,
      chair and envelope conformations, respectively. In (I), intermolecular O-H...O
      hydrogen bonds link the molecules into chains via a co-operative O-H...O-H...O-H
      pattern. In (II), intermolecular O-H...O and O-H...N hydrogen bonds link the
      steroid and water molecules alternately into extended chains.

PMID- 14712054
TI  - The polysulfonylamines bis(methylsulfonamido) sulfone and
      bis(trifluoromethylsulfonamido) sulfone.
AB  - Bis(methylsulfonamido) sulfone, C(2)H(8)N(2)O(6)S(3) or SO(2)(NHSO(2)CH(3))(2),
      was synthesized from imidobis(sulfonyl chloride), HN(SO(2)Cl)(2), and
      bis(trimethylsilyl)methane, CH(2)[Si(CH(3))(3)](2), in chlorotrimethylsilane
      solution. In the solid state, there are two independent molecules linked by two N
      H...O hydrogen bridges into infinite chains parallel to the b axis. The central S
      atoms of the independent molecules each lie on a twofold axis.
      Bis(trifluoromethylsulfonamido) sulfone, C(2)H(2)F(6)N(2)O(6)S(3) or
      SO(2)(NHSO(2)CF(3))(2), was formed by the reaction of trichlorophosphazosulfuryl
      trifluoromethane, Cl(3)PNSO(2)CF(3), with fluorosulfonic acid, FSO(3)H. The
      molecules are connected by bifurcated N-H...O bridges into infinite layers
      parallel to the [001] plane. The central S atom lies on a twofold axis.

PMID- 14712055
TI  - 3 beta,7 alpha,12 alpha-triformyloxy-24-nor-5 beta-chol-22-ene.
AB  - The title compound, alternatively called 24-nor-5 beta-chol-22-ene-3 beta,7
      alpha,12 alpha-triyl triformate, C(26)H(38)O(6), has a cis junction between two
      of the six-membered rings. All three of the six-membered rings have chair
      conformations that are slightly flattened and the five-membered ring has a 13
      beta,14 alpha-half-chair conformation. The 3 beta, 7 alpha and 12 alpha ring
      substituents are axial and the 17 beta group is equatorial. The 3 beta-formyloxy
      group is involved in one weak intermolecular C-H...O bond, which links the
      molecules into dimers in a head-to-head fashion.

PMID- 14712056
TI  - Hydrogen bonding in C-substituted nitroanilines: a chain of R3 3(12)rings in 2
      methanesulfonyl-4-nitroaniline.
AB  - The title compound, C(7)H(8)N(2)O(4)S, exhibits a markedly polarized molecular
      electronic structure. The molecules are linked into a chain of edge-fused
      R(3)(3)(12) rings by two N-H...O[double bond]S hydrogen bonds [H...O = 2.10 and
      2.21 A, N...O = 2.900 (2) and 2.878 (2) A, and N-H...O = 152 and 133 degrees ].

PMID- 14712057
TI  - Methyl 4-nitrophenyl sulfoxide: pi-stacked chains of hydrogen-bonded R2 2(10)
      dimers.
AB  - Molecules of the title compound, C(7)H(7)NO(3)S, are linked into centrosymmetric
      R(2)(2)(10) dimers by paired C-H...O hydrogen bonds, and these dimers are linked
      into [110] chains by a single aromatic pi-pi stacking interaction.

PMID- 14712058
TI  - 6a,6b,12a,12b-Tetrahydrocycloocta[3,4]cyclobuta[1,2][8]annulene.
AB  - The cis,syn,cis-tricyclic [2+2]-dimer of cyclooctatetraene, C(16)H(16),
      crystallizes in space group Pca2(1) with two molecules in the asymmetric unit. An
      extensive network of weak C-H...pi(C[double bond]C) interactions between the two
      independent molecules, A and B, as well as A...A and B...B interactions, are
      observed in the supramolecular assembly. The C-H groups point more towards one C
      atom than to the centre of the C[double bond]C bond. Notable among the
      interactions are bifurcated (cyclobutane)C-H...C[double bond]C contacts that span
      transannularly the eight-membered ring.

PMID- 14712059
TI  - Regioisomeric 4-nitroindazole N1- and N2-(beta-D-ribonucleosides).
AB  - The structures of the isomeric nucleosides 4-nitro-1-(beta-D-ribofuranosyl)-1H
      indazole, C(12)H(13)N(3)O(6), (I), and 4-nitro-2-(beta-D-ribofuranosyl)-2H
      indazole, C(12)H(13)N(3)O(6), (II), have been determined. For compound (I), the
      conformation of the glycosylic bond is anti [chi = -93.6 (6) degrees ] and the
      sugar puckering is C2'-exo-C3'-endo. Compound (II) shows two conformations in the
      crystalline state which differ mainly in the sugar pucker; type 1 adopts the C2'
      endo-C3'-exo sugar puckering associated with a syn base orientation [chi = 43.7
      (6) degrees ] and type 2 shows C2'-exo-C3'-endo sugar puckering accompanied by a
      somewhat different syn base orientation [chi = 13.8 (6) degrees ].

PMID- 14712060
TI  - 1-Bromo-2,6-bis[(pyrazol-1-yl)methyl]benzene.
AB  - The title compound, C(14)H(13)BrN(4), has a planar central unit,
      (C)(2)C(6)H(3)Br, the pendant pyrazole rings forming dihedral angles of 83.8 (3)
      and 89.3 (3) degrees with this plane. The pyrazole rings are oriented such that
      there is an approximate twofold axis coincident with the C-Br bond.

PMID- 14712061
TI  - Intramolecular cyclization of 4,7-bis(2-bromoacetyl)-1-thia-4,7-diazacyclononane.
AB  - The reaction of 1-thia-4,7-diazacyclononane with bromoacetyl bromide in CHCl(3)
      affords the unexpected salt 4-(2-bromoacetyl)-8-oxo-1-thionia-4,7
      diazabicyclo[5.2.2]undecane bromide, C(10)H(16)BrN(2)O(2)S(+).Br(-). Two units of
      the salt are linked by S.Br contacts about a crystallographic inversion centre,
      thus forming dimers that are linked by Br...Br contacts into extended ribbons.
      S...O contacts between these ribbons generate a two-dimensional sheet.

PMID- 14712062
TI  - Evidence of mnt-myc antagonism revealed by mnt gene deletion.
AB  - Myc proteins play a central role in promoting cell proliferation and contribute
      to a diverse array of cancers. My function appears completely dependent on
      heterodimerization with Max through related bHLHZip regions. Max interaction with
      Myc is required for DNA binding at so-called E-box sequences and Myc-dependent
      transcriptional activation. The repressor with similar DNA binding specificity
      raised the possibility that Mnt may serve a general role as a Myc antagonist.

PMID- 14712063
TI  - A new kind of prion: a modified protein necessary for its own modification.
AB  - We recently described an infectious protein (prion) unrelated to amyloid
      formation, that is an enzyme whose precursor can only be activated by the active
      form of the enzyme. All previously described infectious proteins are self
      propagating amyloid forms of chromosomally encoded proteins. The infectious
      enzyme, vacuolar protease B (PrB), can activate its own precursor in an
      indefinitely self-propagating process. Transfer from cell to cell of cytoplasm
      containing active protease B transmits this non-chromosomal gene. The importance
      of this system is that many protein-modifying enzymes may act on themselves, and
      if conditions are right, may become prions as well.

PMID- 14712064
TI  - Muscle-derived stem cells.
AB  - Researchers have identified 2 types of stem cells in skeletal muscle: satellite
      cells and multipotent stem cells (MPSCs). The latter category includes different
      cell populations isolated by various researchers using several techniques. The
      methods used to isolate these cells appear to influence the stem cell
      characteristics of the MPSCs. Although MPSCs and satellite cells could represent
      different stages of maturation of the same progenitor cells, they also could
      represent distinct populations of stem cells that exist in skeletal muscle. This
      article summarizes the recent developments in muscle-derived stem cell research.

PMID- 14712065
TI  - Cdk5 phosphorylation of FAK regulates centrosome-associated miocrotubules and
      neuronal migration.
AB  - Cdk5 is a member of the cyclin-dependent kinase (Cdk) family. Unlike other Cdks
      that promote cell cycle, Cdk5 is activated in postmitotic neurons and critically
      regulates neuronal migration by phosphorylating its substrates during brain
      development. Recently, we found that Cdk5 phosphorylates focal adhesion kinase
      (FAK) at Serine 732 in vitro and is responsible for this phosphorylation in the
      developing brain. Our experiments using a phospho-specific antibody and an S732
      unphosphorylatable mutant FAK suggest that S732 phosphorylation may regulate a
      centrosome-associated microtubule structure to promote nuclear translocation, a
      critical step in neuronal migration. S732 phosphorylation does not directly
      impact on the kinase activity of FAK, but appears to prevent the accumulation of
      FAK at the centrosome. Our study reveals a similarity between Cdk5 and Cdk1 in
      the regulation of neuronal migration and cell division, respectively. In
      addition, our study implicates FAK in a signaling pathway that directly regulates
      microtubules.

PMID- 14712066
TI  - Deregulated repression of c-Jun provides a potential link to its role in
      tumorigenesis.
AB  - The transcription factor c-Jun cooperates with oncogenic alleles of ras in
      malignant transformation. Constitutively active Ras causes, via activation of
      mitogen activated protein kinases, phosphorylation of c-Jun which is essential
      for subsequent target gene activation and tumorigenesis. Studying the mechanisms
      controlling c-Jun activity we found that its transcription activation function is
      actively repressed by a presumably multimeric repressor complex that includes
      histone deacetylase 3 as a critical subunit. Suppression of c-Jun is relieved by
      MAP kinase-mediated phosphorylation and/or titration of inhibitor components. The
      viral tumorigenic counterpart of c-Jun, v-Jun, escapes this inhibition,
      suggesting deregulated transcriptional activity of c-Jun as a relevant cause for
      carcinogenesis.

PMID- 14712067
TI  - Auto-acetylation of transcription factors as a control mechanism in gene
      expression.
AB  - We have shown that the human general transcriptional factor IB (TFIIB) auto
      acetylates specifically at lysine 238 in the presence of acetyl coenzyme A in
      vitro. This is the first case of acetylation of a transcription factor in the
      absence of a factor acetyltransferase (FAT). Acetylation of TFIIB results in a
      stronger interaction with transcription factor IIF (TFIIF) and activated
      transcription in vitro. Cells transfected with mutant TFIIB incapable of auto
      acetylation show decreased levels of transcription in vitro. If auto-acetylation
      of TFIIB occurs in cells, acetyl coenzyme A levels may play an important role in
      the regulation of transcription. In addition, we report for the first time that
      the RAP30 subunit of TFIIF is also auto-acetylated in the presence of acetyl
      coenzyme A in a pH-dependent manner, similarly to TFIIB. This finding strongly
      suggests that auto-acetylation may be more important in regulating gene
      expression than previously believed.

PMID- 14712068
TI  - When pol I goes into high gear: processive DNA synthesis by pol I in the cell.
AB  - Pol I is the most abundant polymerase in E. coli and plays an important role in
      short patch repair. In accord with this role in the cell, the purified polymerase
      exhibits low processivity and high fidelity in vitro. Pol I is also the
      polymerase responsible for leader strand synthesis during ColE1 plasmid
      replication. In a previous publication, we described the generation of a highly
      error-prone DNA polymerase I. Expression of this mutant Pol I results in errors
      during the replication of a ColE1 plasmid. The distribution and spectrum of
      mutations in the ColE1 plasmid sequence downstream the ori indicates that Pol I
      is capable of more processive replication in vivo than previously accepted. Here,
      we review evidence suggesting that Pol I may be recruited into a replisome-like
      holoenzyme and speculate that processive DNA replication by Pol I may play a role
      in recombination-dependent DNA replication in the cell.

PMID- 14712069
TI  - Remodelling the Rad9 checkpoint complex: preparing Rad53 for action.
AB  - DNA damage checkpoints are signal transduction pathways that are activated after
      genotoxic insults to protect genomic integrity. The Rad9 protein functions in the
      DNA damage checkpoint pathway in Saccharomyces cerevisiae and is essential for
      the Mec1-dependent activation of the effector kinase Rad53. We recently described
      the purification of two soluble distinct Rad9 complexes. The large 850 kDa
      complex consists of hypophosphorylated Rad9 and the chaperone proteins Ssa1/2.
      This complex is found both in undamaged cells as well as in cells treated with
      DNA damaging agents. The smaller 560 kDa complex contains hyperphosphorylated
      Rad9, Ssa1/2 and, in addition, Rad53. This complex forms only in cells with
      compromised DNA integrity. Once bound to the smaller complex, Rad53 can be
      activated by in trans autophosphorylation. Here, we propose a model in which the
      large Rad9 complex is remodelled after a genomic insult by chaperone activity to
      a smaller Rad53 activating complex.

PMID- 14712070
TI  - Genetic reprogramming by retroviruses: enhanced suppression of translational
      termination.
AB  - Viruses often exploit or subvert host machinery for their own purposes during
      replication. A search for proteins interacting with the murine leukemia virus
      reverse transcriptase (RT) recently provided a new example of such exploitation.
      RT was found to bind the eukaryotic translational release factor 1 (eRF1), the
      protein that recognizes stop codons and, in complex with eRF3, causes termination
      and polypeptide release from the ribosome. RT is derived from a large Gag-Pol
      polyprotein, and its synthesis requires a translational readthrough, a
      suppression of termination, at a stop codon at the end of the gag gene. The
      binding of eRF1 by RT was found to inhibit eRF1 action, enhance the efficiency of
      readthrough, and thus cause higher levels of RT synthesis. The observations
      suggest that retroviruses manipulate the translational machinery in sophisticated
      ways to fine-tune their own gene expression.

PMID- 14712071
TI  - A novel replication arrest pathway in response to DNA damage.
AB  - DNA damage has been shown to regulate DNA replication both by inhibition of
      origin utilization, and by slowing of replication progression. We have recently
      reported another mechanism by which DNA damage affects replication, in which the
      presence of damaged DNA inhibits, in trans, the initiation of chromosomal
      replication. This inhibition occurs by blocking the association of the
      processivity clamp PCNA with undamaged chromatin. This inhibitory activity is not
      due to sequestration of replication factors by the damaged DNA, rather, it acts
      through generation of a diffusible inhibitor of PCNA loading. The activation of
      this pathway is independent of canonical checkpoint signaling, and, in fact,
      results in activation of the checkpoint. This novel pathway may therefore
      represent an amplification step to stop cell cycle progression in response to
      lower levels of DNA damage.

PMID- 14712072
TI  - The Polo-box domain: a molecular integrator of mitotic kinase cascades and Polo
      like kinase function.

PMID- 14712073
TI  - Attach first, then detach: a role for cyclin B-dependent kinase 1 in coordinating
      proteolysis with spindle assembly.

PMID- 14712074
TI  - Role of p21WAF1 in the cellular response to UV.
AB  - UV or g irradiation mediated DNA damage activates p53 and induces cell cycle
      arrest. Induction of cyclin dependent kinase inhibitor p21WAF1 by p53 after DNA
      damage plays an important role in cell cycle arrest after gamma irradiation. The
      p53 mediated cell cycle arrest has been postulated to allow cells to repair the
      DNA damage. Repair of UV damaged DNA occurs primarily by the nucleotide excision
      pathway (NER). It is known that p21WAF1 binds PCNA and inhibits PCNA function in
      DNA replication. PCNA is also required for repair by NER but there have been
      conflicting reports on whether p21WAF1 can inhibit PCNA function in NER. It has
      therefore been difficult to integrate the UV induced cell cycle arrest by p21 in
      the context of repair of UV damaged DNA. A recent study reported that p21WAF1
      protein is degraded after low but not high doses of UV irradiation, that cell
      cycle arrest after UV is p21 independent, and that at low dose UV irradiation
      p21WAF1 degradation is essential for optimal DNA repair. These findings shed new
      light on the role of p21 in the cellular response to UV and clarify some
      outstanding issues concerning p21WAF1 function.

PMID- 14712075
TI  - To be or not to be ubiquitinated?
AB  - Levels of p21, a cyclin-dependent kinase (CDK) inhibitor, are controlled in part
      at the post-translational level by protein degradation. Although the signaling
      pathways leading to p21 degradation have not yet been fully elucidated, it is
      evident that p21 ubiquitination is an essential factor in its degradation. We
      discuss that, with the only notable exception of ornithine decarboxylase,
      ubiquitination appears to be a prerequisite for proteasomal degradation rather
      than an unnecessary byproduct of such proteolysis.

PMID- 14712076
TI  - Thermodynamic cooperativity and kinetic proofreading in DNA damage recognition
      and repair.
AB  - In humans UV-induced cyclobutane thymine dimers are excised by the joint action
      of six repair factors, RPA, XPA, XPC, TFIIH, XPG, and XPF.ERCC1. Yet, in vitro
      assays show that none of these six factors is capable of detectably
      discriminating thymine dimer-containing DNA from undamaged DNA. We show how two
      elementary principles in macromolecular recognition, (1). cooperativity and (2).
      kinetic proofreading, are utilized to confer specificity to the repair system
      where none exists at the individual repair factor level and enable human cells to
      excise thymine dimers with a physiologically relevant specificity and at a
      biologically acceptable rate.

PMID- 14712077
TI  - Beta-catenin and cyclin D1: connecting development to breast cancer.
AB  - Beta-catenin and cyclin D1 have attracted considerable attention due to their
      proto-oncogenic roles in human cancer. The finding of cyclin D1 as a direct
      target gene of beta-catenin in colon cancer cells led to the assumption that
      cyclin D1 upregulation is pivotal to beta-catenin's oncogenicity. Our recent
      paper shows that this is not the case; cyclin D1 dampens the oncogenicity of
      activated beta-catenin (MMTV-DN89beta-catenin). The relationships and
      dependencies of beta-catenin and cyclin D1 point to distinct, essential and
      sequential roles during alveologenesis. These results support the concept that
      both beta-catenin's and cyclin D1's actions are more sophisticated than simple
      acceleration of the cell cycle clock. These proteins are employed at critical
      junctures involving cell fate decisions that we speculate require specific types
      of cell cycle to traverse.

PMID- 14712078
TI  - H2AX may function as an anchor to hold broken chromosomal DNA ends in close
      proximity.
AB  - The histone H2A variant, H2AX, is a core component of chromatin that is
      phosphorylated in chromatin flanking DNA double strand breaks (DSBs). Here, we
      summarize H2AX functions and outline a specific "anchoring" model, that can
      explain the translocation prone phenotype of H2AX-deficient and H2AX/p53
      deficient mice. We also discuss how this model of H2AX function could account for
      some aspects of the genomic instability and cancer prone human phenotypes
      associated with Ataxia Telangiectasia (AT), Nijmegen Breakage Syndrome (NBS),
      Ataxia Telangiectasia Like Disorder (ATLD), and Bloom's Syndrome (BS).

PMID- 14712079
TI  - HIF-1: a target for cancer, ischemia and inflammation--too good to be true?

PMID- 14712080
TI  - HIF-1's relationship to oxygen: simple yet sophisticated.
AB  - HIF-1 is a transcription factor which acts as a master regulator coordinating
      oxygen homeostasis. An oxygen sensitive signal controlling HIF-1 is provided by
      enzymatic hydroxylation reactions which require molecular oxygen and modify
      specific prolyl and asparaginyl residues in the HIF a subunit. These act as
      switches-- enabling capture by a specific ubiquitin ligase and preventing
      transactivator recruitment. An important challenge is to understand how this
      simple principle is used to tailor the oxygen response system to the diverse
      settings that occur in complex organisms such as ourselves. The emerging picture
      is of many parameters which are likely to contribute, including cofactor
      availability and regulated expression of the hydroxylase enzymes.

PMID- 14712081
TI  - Dead cells don't form tumors: HIF-dependent cytotoxins.
AB  - Elimination or reduction of tumor burden is the primary goal of cancer therapy.
      Strategies to achieve this goal with the fewest adverse effects to the patient
      are an area of intense investigation. Elevated protein levels of hypoxia
      inducible factor (HIF) are commonly found in solid tumors, while rarely found in
      healthy tissue. Numerous studies have suggested that HIF activity is essential
      for the development of solid tumors. Thus, inhibition of HIF represents an
      attractive therapeutic target for eradicating tumors. The search for small
      molecules that target and inhibit HIF activity is currently underway. We propose
      an alternate approach: to directly target and kill HIF-activated tumor cells.
      This approach is advantageous in that cells with activated HIF will be eliminated
      directly. Specific elimination of HIF-activated cells represents a potential
      mechanism for inhibiting tumor growth, with the potential advantage of sparing
      the patient of the normal tissue toxicity associated with current treatment
      options.

PMID- 14712082
TI  - Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival
      pathway and therapy target.
AB  - Over 50 genes are inducible by hypoxia, via hypoxia inducible factor 1alpha (HIF
      1alpha). Carbonic anhydrase IX (CAIX) is one of the most inducible and most
      uniformly induced genes and because of its stability and membrane location
      provides a reliable histochemical marker of hypoxia. Recent studies have shown
      the importance of pH in cell death under hypoxia, thus mechanisms of pH
      regulation are likely to be vital pathways for survival. Carbonic anhydrases have
      a widespread role in normal tissues in regulating pH, with 14 isoforms described,
      so inhibition may have substantial normal tissue toxicity. Selective nonmembrane
      permeable inhibitors are available and may synergise with chemotherapy agents
      more active in acid conditions. CAIX has a major role in regulating hydrogen ion
      (H+) flux and blockade of CAIX results in increased cell death under hypoxia,
      indicating that it is one mechanism of hypoxic adaptation. As it is commonly
      expressed in tumours with the worst prognosis it is a potential target for
      therapy.

PMID- 14712083
TI  - An unexpected role for hypoxic response: oxygenation and inflammation.
AB  - The eradication of invading microorganisms depends initially on innate immunity
      mechanisms that preexist in all individuals and act within minutes of infection.
      Pathogen spread is often countered by an inflammatory response that recruits more
      effector molecules and cells of the innate immune system from local blood
      vessels, while inducing clotting farther downstream so that pathogens cannot
      spread throughout the blood. If a microorganism crosses an epithelial barrier and
      begins to replicate in the tissues of the host, it is, in some cases, immediately
      recognized by the mononuclear phagocytes, or macrophages, that reside in tissues.
      Macrophages mature continuously from circulating monocytes that leave the
      circulation to migrate into tissues throughout the body. The second major family
      of phagocytes, the neutrophils or polymorphonuclear leukocytes (PMNs) are short
      lived cells that are abundant cells in the blood but are not present in healthy
      tissues. Both phagocytic cell types play a key role in innate immunity because
      they can recognize, ingest and destroy many pathogens without the aid of an
      adaptive immune response. This infiltration of neutrophils and later macrophages
      to the site of bacterial infection is tightly linked with the need of these
      immune defense cells to respond to the tissue microenvironment.

PMID- 14712084
TI  - Targeting topoisomerase I to inhibit hypoxia inducible factor 1.
AB  - HIF-1 is a key factor in cancer progression. Efforts are underway to identify and
      develop small molecules that inhibit HIF-1 transcriptional activity. What are the
      best targets and the best ways to develop HIF-1 inhibitors are open questions.
      However, several "nonselective" HIF-1 inhibitors have been identified, which are
      either in the clinic or under development. In this article, we discuss how
      topoisomerase I poisons, which inhibit HIF-1a protein accumulation and
      transcriptional activity, can be "rationally" used to target HIF-1 for cancer
      therapy.

PMID- 14712085
TI  - Role of raf isoforms in signal transduction pathways relevant to leukemia cell
      proliferation.
AB  - The invited commentary is addressed to the paper of Shelton et al published in
      this issue of Cell Cycle. The intracellular pathways that control cell growth
      constitute a complex nexus of signaling interactions that serve to regulate cell
      proliferation, differentiation and apoptosis. Dysregulation of these processes
      leads to the loss of control of cell growth that is characteristic of malignancy.
      Understanding cell signaling is a major challenge for modern biological research.
      One way to begin to unravel the intricate web of signaling pathways is to
      investigate the effects of mutant forms of key component proteins. One such
      protein is the serine/threonine-specific protein kinase, Raf.

PMID- 14712086
TI  - FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2
      monoubiquitination.
AB  - Monoubiquitination of FANCD2 is a key step in the DNA damage response pathway
      involving Fanconi anemia proteins and the breast cancer susceptibility gene
      products, BRCA1 and BRCA2. One critical unresolved issue is the identity of the
      ubiquitin ligase responsible for this reaction. Two proteins, BRCA1 and
      FANCL(PHF9), have been suggested to be this ligase. Here we found that FANCL, but
      not BRCA1, evolutionarily co-exists with FANCD2 in several species. Moreover, the
      proportion of FANCD2 in chromatin and nuclear matrix is drastically reduced in a
      cell line mutated in FANCL, but not in that mutated in BRCA1. This defective
      distribution of FANCD2 in the FANCL-mutant cell line is likely due to its
      defective monoubiquitination, because the monoubiquitinated FANCD2 preferentially
      associates with chromatin and nuclear matrix, whereas non-ubiquitinated FANCD2
      largely resides in the soluble fraction. Our data support the notion that FANCL,
      but not BRCA1, is the likely ligase for FANCD2 monoubiquitination.

PMID- 14712087
TI  - Structure predictions and interaction studies indicate homology of separase N
      terminal regulatory domains and Drosophila THR.
AB  - The final resolution of sister chromatid cohesion during mitotic and meiotic
      divisions is mediated by activation of separase which cleaves a cohesin complex
      subunit. The structural basis of separase regulation is unknown. Separases from
      different eukaryotes share almost no sequence similarity, especially within the
      large N-terminal domain that precedes the protease domain except in Drosophila
      melanogaster. Moreover, sequence similarity among securin proteins, which
      associate as regulatory subunits with separase, is restricted to the signals that
      promote the mitotic degradation required for separase activation. Here, we
      address the surprising divergence of separase and securin sequences. The absence
      of an extended N-terminal separase domain in dipteran species is shown to be
      correlated with the expression of an extra regulatory subunit (THR). The
      interactions of THR with separase and securin in Drosophila melanogaster are
      analogous to those of the human N-terminal separase domain with its C-terminal
      domain and securin. Even heterologous interactions between Drosophila and human
      separase complex components occur in yeast two-hybrid experiments. Tertiary
      structure predictions reveal alpha-alpha superhelix folds in both THR and the N
      terminal domains of nondipteran separases. The compatibility of these folds with
      a wide range of primary sequences has likely allowed the rapid divergence of
      THR/N-terminal separase sequences and securins, which contact this region.

PMID- 14712088
TI  - B-raf and insulin synergistically prevent apoptosis and induce cell cycle
      progression in hematopoietic cells.
AB  - FDC-P1 hematopoietic cells were conditionally transformed to grow in response to
      (delta)B Raf:ER, (delta)Raf-1:ER or DA-Raf:ER in which the hormone binding domain
      of the estrogen receptor (ER) was linked to the N-terminal truncated (delta) Raf
      genes. When these cells were deprived of IL-3 or beta-estradiol for 24 hrs, they
      exited the cell cycle and underwent apoptosis. FD/(delta)Raf-1:ER and FD/(delta)A
      Raf:ER, but not FD/(delta)B-Raf:ER cells, were readily induced to re-enter the
      cell cycle after addition of beta-estradiol or IL-3. Deprived FD/(delta)Raf-1:ER,
      but not FD/(delta)B-Raf:ER cells, expressed activated forms of MEK1 and ERK after
      beta-estradiol or IL-3 stimulation. Insulin or beta-estradiol alone did not
      induce FD/(delta)B-Raf:ER cells to re-enter the cell cycle, whereas cell cycle
      entry was observed upon their co-addition. Apoptosis was prevented in FD/(delta)B
      Raf:ER cells when they were cultured in the presence of IL-3 or beta-estradiol,
      whereas they underwent apoptosis in their absence. Insulin by itself did not
      prevent apoptosis, however, upon DB-Raf:ER or DRaf-1:ER activation and addition
      of insulin, more than an additive effect was observed in both lines indicating
      that these path- ways synergized to prevent apoptosis. Raf isoforms differ in
      their abilities to control apoptosis and cell cycle progression and B-Raf
      requires insulin-activated pathways for full antiapoptotic and proliferative
      activity.

PMID- 14712089
TI  - Differential kinetochore requirements for establishment and maintenance of the
      spindle checkpoint are dependent on the mechanism of checkpoint activation in
      Saccharomyces cerevisiae.
AB  - The spindle checkpoint in the yeast Saccharomyces cerevisiae is an intracellular
      signal transduction pathway comprised of two branches that inhibit two different
      mitotic transitions in cells treated with benzimidazole drugs such as nocodazole.
      The kinetochore is an integral component of the MAD2 branch of the spindle
      checkpoint pathway. Current models propose that the kinetochore is required for
      both the establishment and maintenance of the spindle checkpoint but a role for
      the kinetochore in the maintenance of spindle checkpoint in yeast has never been
      directly tested. We used a temperature sensitive ndc10-1 mutant to inactivate
      kinetochores before and after arresting cells in mitosis to determine the role of
      kinetochores in the establishment and maintenance of the spindle checkpoint. We
      show that both establishment and maintenance requires kinetochore function in
      response to spindle damage induced by benzimidazole drugs. Excess expression of
      the Mps1 protein kinase causes wild type cells and ndc10-1 cells to arrest in
      mitosis. Unlike the spindle checkpoint arrest activated by benzimidazoles, this
      arrest can be maintained independently of kinetochores. The arrest induced by
      excess Mps1p is independent of BUB2. Therefore, mitotic arrest induced by excess
      Mps1p expression is due to the action of the MAD2 branch of the spindle
      checkpoint pathway and excess Mps1p acts downstream of the kinetochore.

PMID- 14712090
TI  - Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl2 ratio and
      induces apoptosis independent of cell cycle association.
AB  - Anti-cancer properties of palm oil have been attributed to the presence of
      tocotrienols and carotenoids. Studies from various laboratories have shown that
      tocotrienol-rich fraction (TRF) of palm oil inhibits cell growth and induces
      apoptosis in both preneoplastic and neoplastic cells. However, the mechanism by
      which TRF induces apoptosis remains largely unknown. Since several
      chemopreventive agents have been shown to utilize p53 pathway in negative
      regulation of cell growth, using human colon carcinoma RKO cells which express
      wild type p53, we investigated the effect of TRF on components of p53 signaling
      network. Treatment of cells with TRF resulted in a dose- and time- dependent
      inhibition of growth and colony formation. Further, TRF treatment of RKO cells
      resulted in the induction of WAF1/p21 which appears to be independent of cell
      cycle regulation and is transcriptionally upregulated in p53 dependent fashion.
      These results were further confirmed by using cells that express luciferase from
      a p53 responsive promoter where TRF treatment leads to activation of p53 reporter
      activity. TRF treatment also resulted in alteration in Bax/Bcl2 ratio in favor of
      apoptosis, which was associated with the release of cytochrome c and induction of
      apoptotic protease-activating factor-1. This altered expression of Bcl2 family
      members triggered the activation of initiator caspase-9 followed by activation of
      effector caspase-3. These signaling cascades lead to condensed chromatin, DNA
      fragmentation and shrinkage of cell membrane resulting into apoptosis. Our data
      suggest that TRF-induced apoptosis in colon carcinoma cells is mediated by p53
      signaling network which appears to be independent of cell cycle association.

PMID- 14712091
TI  - Altered expression of Chk1 disrupts cell cycle remodeling at the midblastula
      transition in Xenopus laevis embryos.
AB  - Studies in several model systems, including Xenopus laevis oocytes and embryos,
      have indicated that the checkpoint kinase, Chk1, is required for early
      development, even in the absence of damaged or unreplicated DNA. Chk1 is
      transiently activated at the midblastula transition (MBT) in Xenopus, a time when
      the cell cycle remodels from rapid embryonic cleavage cycles to longer, more
      regulated somatic cell cycles. To better understand the role of Chk1 in cell
      cycle remodeling, mRNA encoding Chk1 was microinjected into 1-cell stage embryos,
      and the effects on both the MBT and on the expression of several cell cycle
      regulators were examined. Zygotic transcription, a hallmark of the MBT that
      depends upon the nucleocytoplasmic (N/C) ratio, was blocked, as was degradation
      of maternal cyclin E, an event of the MBT that occurs independent of the N/C
      ratio. Levels of mitotic cyclins were elevated throughout early development,
      consistent with cell cycle arrest at G2/M. In these embryos, Cdc25A level was
      low, whereas Cdc25C level was not affected. Furthermore, the level of Wee1
      increased at 6 hrs post-fertilization (pf), the time at which the MBT normally
      occurs, even though these embryos did not demonstrate any known markers of the
      MBT. These studies suggest that in addition to targeting Cdc25A for degradation,
      Chk1 may also function in cell cycle remodeling at the MBT by stabilizing Wee1
      until it is replaced by the somatic Wee2 protein during gastrulation.

PMID- 14712092
TI  - Cell cycle regulation of NF-YC nuclear localization.
AB  - NF-Y is a trimeric activator with histone fold, HFM, subunits that binds to the
      CCAAT-box and is required for a majority of cell cycle promoters, often in
      conjunction with E2Fs. In vivo binding of NF-Y is dynamic during the cell cycle
      and correlates with gene activation. We performed immunofluorescence studies on
      endogenous, GFP- and Flag-tagged overexpressed NF-Y subunits. NF-YA, NF-YB are
      nuclear proteins. Unexpectedly, NF-YC localizes both in cytoplamatic and nuclear
      compartments and its nuclear localization is determined by the interaction with
      its heterodimerization partner NF-YB. Most importantly, compartmentalization is
      regulated during the cell cycle of serum restimulated NIH3T3 cells, accumulating
      in the nucleus at the onset of S phase. These data point to the control of HFM
      heterodimerization as an important layer of NF-Y regulation during cell cycle
      progression.

PMID- 14712093
TI  - Persistence length of chromatin determines origin spacing in Xenopus early-embryo
      DNA replication: quantitative comparisons between theory and experiment.
AB  - In Xenopus early embryos, replication origins neither require specific DNA
      sequences nor is there an efficient S/M checkpoint, even though the whole genome
      (3 billion bases) is completely duplicated within 10-20 minutes. This leads to
      the "random-completion problem" of DNA replication in embryos, where one needs to
      find a mechanism that ensures complete, faithful, timely reproduction of the
      genome without any sequence dependence of replication origins. We analyze recent
      DNA replication data in Xenopus laevis egg extracts and find discrepancies with
      models where replication origins are distributed independently of chromatin
      structure. Motivated by these discrepancies, we have investigated the role that
      chromatin looping may play in DNA replication. We find that the loop-size
      distribution predicted from a wormlike-chain model of chromatin can account for
      the spatial distribution of replication origins in this system quantitatively.
      Together with earlier findings of increasing frequency of origin firings, our
      results can explain the random-completion problem. The agreement between
      experimental data (molecular combing) and theoretical predictions suggests that
      the intrinsic stiffness of chromatin loops plays a fundamental biological role in
      DNA replication in early-embryo Xenopus in regulating the origin spacing.

PMID- 14712094
TI  - Flavopiridol inhibits the growth of GL261 gliomas in vivo: implications for
      malignant glioma therapy.
AB  - The mechanism of action of many chemotherapeutic agents targets the cell cycle.
      Recently, we demonstrated cytotoxic and other anti-tumor effects of flavopiridol,
      the first synthetic cyclin dependent kinase (CDK) inhibitor to enter clinical
      trials, on the murine GL261 glioma cell line in vitro (Newcomb et al., Cell Cycle
      2003; 2:243). Given that flavopiridol has demonstrated anti-tumor activity in
      several human xenograft models, we wanted to evaluate it for anti-glioma activity
      in vivo in our established subcutaneous and intracranial GL261 experimental tumor
      models. In particular, the intracranial animal model recapitulates many of the
      histopathological and biological features of human high-grade glioma including
      both necrosis with pseudopalisading and invasion of the brain adjacent to tumor.
      Here we tested the activity of flavopiridol against tumors formed by GL261 cells,
      first as subcutaneous implants, and then in the intracranial model. We
      demonstrate efficacy of flavopiridol as a single modality treatment in delaying
      tumor growth in both animal models. We hypothesize that flavopiridol treatment
      induced tumor growth delay by two possible mechanisms involving growth arrest
      combined with recruitment of tumor cells to S-phase. Based on our findings,
      flavopiridol should be considered as a treatment approach for patients with high
      grade glioma.

PMID- 14712095
TI  - Laparoscopy-assisted D2 subtotal gastrectomy in early gastric cancer.
AB  - The purpose of this study is to prove the safety and efficacy of laparoscopy
      assisted subtotal gastrectomy and D2 lymph node dissection using 4 ports and an
      EEA stapler with a Billroth I anastomosis. From 1999 to 2001, 20 patients with
      EGC located in the distal stomach underwent laparoscopy-assisted Billroth I
      gastrectomy (LABIG). A 4-port-technique was performed for omentectomy, vascular
      ligation, and D2 lymph node dissection. A mini-incision was created between the
      two ports in the epigastric area and a gastroduodenal anastomosis with an EEA
      stapler and a distal resection was performed. The mean operating time was 261.8
      (170-410) minutes. There was one postoperative complication without any
      intraoperative transfusions or perioperative mortality. The number of harvested
      nodes was 31.9 +/- 11.4. Mean distance from the lesion to the margin of resection
      was 5.3 +/- 2.2 cm proximally and 4.0 +/- 2.0 cm distally. On average, oral
      liquids were started at the 4.7th (3rd-8th) postoperative day. LABIG is a safe
      and effective way of performing D2 gastrectomy in terms of morbidity and
      oncological principles. A randomized controlled clinical study to compare long
      term survival and quality of life is warranted.

PMID- 14712096
TI  - Dispersive pad site burns with modern radiofrequency ablation equipment.
AB  - Pad burns during or after radiofrequency ablation (RFA) are a skin complication
      probably underreported in the literature. We report on 4 severe pad burns, deep
      second and third degree, in 3 patients undergoing radiofrequency ablation of
      liver malignancies, 1 percutaneously and the other 2 after laparotomy. All burns
      occurred at the leading edge or at the corner of the pads attached to the
      patients' thighs. Potential causes leading to the burns are discussed. Current
      dispersive pad designs do not prevent the leading edge phenomenon and subsequent
      burns. Further developmental work in the pad design with the possibility of skin
      temperature monitoring via temperature sensors under the leading pad edge is
      needed.

PMID- 14712097
TI  - Prevention of dispersive pad skin burns during RFA by a simple method.

PMID- 14712098
TI  - Preserving the superior rectal artery in laparoscopic sigmoid resection for
      complete rectal prolapse.
AB  - Sigmoid resection is indicated in the treatment of complete rectal prolapse (CRP)
      in patients with prolonged colorectal transit time (CTT). Its use, however, has
      been limited because of fear of anastomotic leakage. This study challenges the
      current practice of dividing the mesorectum by prospectively evaluating the
      impact of sparing the superior rectal artery (SRA) on leak rates after
      laparoscopic sigmoid resection (LSR) for CRP. During a 30-month period, data on
      33 selected patients with CRP were prospectively collected. Three patients were
      withdrawn from the analysis, as they had neither resection nor anastomosis.
      Twenty-nine women and 1 man (median age 55 range 21-83 years) underwent LSR with
      preservation of SRA for a median CRP of 8 (3-15) cm. There were 20 ASA I and 10
      ASA II patients. Ten patients had undergone previous surgery. Four patients
      complained of dyschezia, whereas incontinence was present in 26 patients. Anal
      ultrasound showed isolated internal sphincter defects in 2 patients. Four young
      adults (21-32 years) had normal CTT, whereas 26 older patients had a median CTT
      of 5(4-6) days. Defecography demonstrated 10 enteroceles, two sigmoidoceles, and
      one rectal hernia through the levator ani muscle. Mortality was nil. Median
      operating room time was 180 (120-330) min, suprapubic incision length 5(3-7) cm,
      estimated blood loss 150 (50-500) mL, specimen length 20 (12-45) cm, solid food
      resumption 3(1-6) days, and length of stay 4.5(2-7) days. Thirty-day
      complications were not related to anastomosing and occurred in 20% of the
      patients. Median follow-up was 34.1 (18-48) months. One patient had a recurrence.
      Although the evidence provided by the present study suggests that sparing SRA has
      a favorable impact on anastomotic leak rates, these nonrandomized results need
      further evaluation. The division of the mesorectum at the rectosigmoid junction
      seems not necessary, and its sparing should therefore be considered as it may
      contain anastomotic leak rates.

PMID- 14712099
TI  - Can laparoscopic hernia repair alter function and volume of testis? Randomized
      clinical trial.
AB  - Testicular atrophy is a sequela of inguinal hernioplasty. The purpose of this
      study was to evaluate the effects of Lichtenstein (LHR) and laparoscopic totally
      extraperitoneal (TEP) hernia repair techniques on testicular function and volume.
      This study is a randomized prospective clinical trial with the blind assessment
      of outcome. A total of 26 patients who underwent elective herniorrhaphy for groin
      hernia were included in the study. Each patient was randomly assigned into one of
      two groups: either TEP or LHR (n = 13 for each). Six of the patients had
      bilateral hernia (n = 3 for each group). Luteinizing hormone (LH), follicle
      stimulating hormone (FSH), testosterone levels, and testicular volume by Doppler
      ultrasonography were detected just before and 3 months after the operation. LH,
      FSH levels did not change, when compared preoperative and postoperatively in both
      groups. Testicular volume and testosterone levels were observed to be
      significantly decreased after TEP when compared with LHR while no significant
      preoperative changes were observed between those groups. This affected the
      testicular volume in normal limits. TEP or LHR could not affect LH, FSH,
      testosterone values, but TEP could lead a decreasing effect on volume of testis
      in normal limits.

PMID- 14712100
TI  - Combined procedures in laparoscopic surgery.
AB  - With advancements in minimal access surgery, combined laparoscopic procedures are
      now being performed for treating coexisting abdominal pathologies at the same
      surgery. In our center, we performed 145 combined surgical procedures from
      January 1999 to December 2002. Of the 145 procedures, 130 were combined
      laparoscopic/endoscopic procedures and 15 were open procedures combined with
      endoscopic procedures. The combination included laparoscopic cholecystectomy,
      various hernia repairs, and gynecological procedures like hysterectomy,
      salpingectomy, ovarian cystectomy, tubal ligation, urological procedures,
      fundoplication, splenectomy, hemicolectomy, and cystogastrostomy. In the same
      period, 40 patients who had undergone laparoscopic cholecystectomy and 40
      patients who had undergone ventral hernia repair were randomly selected for
      comparison of intraoperative outcomes with a combined procedure group. All the
      combined surgical procedures were performed successfully. The most common
      procedure was laparoscopic cholecystectomy with another endoscopic procedure in
      129 patients. The mean operative time was 100 minutes (range 30-280 minutes). The
      longest time was taken for the patient who had undergone laparoscopic splenectomy
      with renal transplant (280 minutes). The mean hospital stay was 3.2 days (range 1
      21 days). The pain experienced in the postoperative period measured on the visual
      analogue scale ranged from 2 to 5 with a mean of 3.1. Of 145 patients who
      underwent combined surgical procedures, 5 patients developed fever in the
      immediate postoperative period, 7 patients had port site hematoma, 5 patients
      developed wound sepsis, and 10 patients had urinary retention. As long as the
      basic surgical principles and indications for combined procedures are adhered to,
      more patients with concomitant pathologies can enjoy the benefit of minimal
      access surgery. Minimal access surgery is feasible and appears to have several
      advantages in simultaneous management of two different coexisting pathologies
      without significant addition in postoperative morbidity and hospital stay.

PMID- 14712101
TI  - Surgical clip found in duodenal ulcer after laparoscopic cholecystectomy.
AB  - The wide use of surgical clips in laparoscopic surgery has led to a variety of
      complications. We describe two cases in which a surgical clip was incorporated
      into a duodenal ulcer after laparoscopic cholecystectomy. The presenting symptom
      was acute gastrointestinal bleeding. Both patients were treated endoscopically,
      and the bleeding stopped after the clip was removed from the ulcer base. Although
      the mechanism by which a surgical clip migrates into the duodenum is unclear, we
      recommend meticulous Calot's triangle dissection and removal of any wandering or
      misplaced clips. Endoscopic removal is recommended when a surgical clip is
      discovered in a bleeding ulcer.

PMID- 14712102
TI  - Emergent laparoscopic reduction of acute gastric volvulus with anterior
      gastropexy.
AB  - Gastric volvulus is characterized by abnormal rotation of the stomach around an
      axis made by two fixed portions. Symptoms of gastric volvulus range from anemia
      and weight loss to severe epigastric or chest pain associated with nonproductive
      vomiting or upper gastrointestinal bleeding. Ischemia, necrosis, and perforation
      will occur if this condition remains untreated. We report a case of a 92-year-old
      patient with acute gastric volvulus treated with laparoscopic reduction and
      anterior gastropexy. We suggest that the laparoscopic approach to gastric
      volvulus is safe and feasible and should be considered. High-risk and elderly
      patients can particularly benefit from minimally invasive access. Anterior
      gastropexy palliates the symptoms and can be considered a definitive treatment in
      this patient population.

PMID- 14712103
TI  - Fishbone perforation of the small bowel: laparoscopic diagnosis and
      laparoscopically assisted management.
AB  - We report a patient with small bowel perforation caused by a piece of fishbone
      diagnosed by laparoscopy and treated with laparoscopically assisted surgery
      through a small incision. This uncommon cause of peritonitis and the role of
      laparoscopy for this condition are discussed.

PMID- 14712104
TI  - Laparoscopic treatment for intussusception of the small intestine in the adult.
AB  - The term intussusception refers to a spontaneous invagination of a portion of the
      intestine into another bowel loop. Its incidence is higher in children, but in
      adults it causes 1% to 5% of intestinal obstructions. The diagnosis of
      intussusception in the adult is difficult due to the variability of the symptoms.
      The condition may be chronic, intermittent, or acute. Surgical intervention is
      necessary in all cases and in up to 90% of cases an organic lesion inside the
      invaginated part of the bowel is found to be the lead point. The laparoscopic
      approach offers both a diagnostic and therapeutic option. Laparoscopy may be used
      as the final diagnostic or therapeutic tool for intussusception in the adult.

PMID- 14712105
TI  - Laparoscopic splenectomy for a huge splenic cyst without preoperative drainage:
      report of a case.
AB  - Laparoscopic splenectomy currently is a safe procedure and offers better cosmetic
      results, less pain, and a shorter hospital stay than the traditional open
      procedure. However, there have been only a few reports of laparoscopic removal of
      giant splenic cysts. An 18-year-old woman was admitted with abdominal fullness.
      CT scans and MRI images of the upper abdomen revealed a cystic mass having a
      diameter of 19 cm. Preoperative diagnosis was a large splenic cyst, and
      laparoscopic splenectomy with intraoperative cyst drainage (amount of drained
      fluid: 3,000 mL) was performed. Histologically, almost the entire cyst wall was
      lined with fibrous tissue, but a small portion was covered with stratified
      squamous epithelium. The final diagnosis was epidermoid cyst. The postoperative
      course was uneventful. Laparoscopic splenectomy should be tried first even in
      patients with a huge cyst, and intraoperative drainage under laparoscopic
      guidance facilitates laparoscopic splenectomy.

PMID- 14712106
TI  - Laparoscopic repair of Morgagni diaphragmatic hernia: a new case.
AB  - A large diaphragmatic Morgagni-type hernia that was incidentally discovered in an
      8-month-old girl is described. The diaphragmatic defect was closed through
      laparoscopy. The latter approach is felt to be superior over conventional surgery
      and is therefore recommended in similar cases.

PMID- 14712107
TI  - Retroperitoneoscopic deroofing of a giant renal cyst in a solitary functioning
      hydronephrotic kidney with a 3-port technique.
AB  - To explore the safety and feasibility of performing retroperitoneoscopic renal
      cystectomy in a case of massive giant renal cyst in a solitary hydronephrotic
      renal unit. We have described the retroperitoneal three-trocar technique. The
      role of laparoscopic renal cyst ablation in giant symptomatic renal cysts and non
      polycystic kidney disease has been discussed. The patient was successfully
      managed by retroperitoneoscopic deroofing using a three-port technique. The
      operating room time was 90 minutes and her hospital stay lasted 54 hours. The
      fluid cytology and cyst histology were negative for tumor. Complete resolution of
      the cyst was noted on a follow-up ultrasound done after 2 months. Currently at 9
      month follow up, the patient is ultrasonographically free of any cyst recurrence
      or hydronephrosis. The retroperitoneal approach is feasible for marsupializing
      giant symptomatic renal cysts and appears to be safe for solitary symptomatic
      renal units too. It shortens the overall operating time and avoids the
      complications and demerits of transperitoneal access.

PMID- 14712108
TI  - Comprehensive review of minimally invasive, specifically laparoscopic approaches
      to pancreatic pseudocysts.

PMID- 14712109
TI  - Complications in endoscopic sinus surgery.

PMID- 14712111
TI  - Intravenous antibiotics for chronic rhinosinusitis: are they effective?
AB  - PURPOSE OF REVIEW: Antibiotics have been used commonly in chronic rhinosinusitis,
      often because chronic rhinosinusitis has features of a prolonged bacterial
      sinusitis, including abnormal CT findings and positive bacterial cultures. The
      advent of peripherally inserted central catheters has enabled outpatient
      parenteral antibiotic therapy to become a convenient means of delivering potent
      antibiotics for various conditions when oral antibiotics may not be effective or
      appropriate. Chronic rhinosinusitis has been included as a condition that may
      benefit from outpatient parenteral antibiotic therapy; however, there are few
      studies that document its success and, furthermore, chronic rhinosinusitis may
      not always be an infectious process. RECENT FINDINGS: Three recent uncontrolled
      retrospective studies examined outpatient parenteral antibiotic therapy in
      chronic rhinosinusitis. In one series outpatient parenteral antibiotic therapy
      was used as an adjunct to sinus surgery, in another it was used as an alternative
      to sinus surgery in the pediatric population, and in the third it was used as
      temporary resolution for adult patients who had failed other therapies including
      sinus surgery. Short-term success rates were reported in the range of 29 to 89%,
      but relapse rates were as high as 89%. Complication rates in theses studies
      ranged from 14 to 26%, including medication reactions and intravenous line
      problems. SUMMARY: The role of outpatient parenteral antibiotic therapy in the
      treatment of chronic rhinosinusitis has not been universally established.
      Although outpatient parenteral antibiotic therapy may have a role in avoiding
      sinus surgery in select pediatric populations, the contribution to a lasting
      resolution in adult patients is less clear and there are possible complications.
      Recognizing subsets of chronic rhinosinusitis patients for whom outpatient
      parenteral antibiotic therapy is appropriate will be the challenge for the
      future.

PMID- 14712112
TI  - Nasal irrigations: good or bad?
AB  - PURPOSE OF REVIEW: Nasal irrigations are often mentioned as adjunctive measures
      in treating many sinonasal conditions. Despite their widespread use, much
      mystique and uncertainty exist about the indications and therapeutic mechanisms
      of nasal irrigations. Anecdotal evidence and poorly controlled studies add to the
      confusion. Recent evidence challenges some of the assumptions underlying the use
      of nasal irrigations. RECENT FINDINGS: Studies of nasal irrigations continue to
      report the benefits in managing sinonasal complaints. Apart from improved patient
      symptomatology, prescription medication use is often decreased. When nasal
      irrigations are combined with other medical modalities, patients with chronic
      sinusitis may not require surgical intervention as often. In particular, patients
      using hypertonic saline nasal irrigations reported better outcomes. Different
      devices and techniques exist. Positive-pressure and negative-pressure methods are
      probably more effective than nebulizers. Furthermore, the popular belief that
      nasal irrigations need to be sterile is in question. SUMMARY: Nasal irrigations
      should no longer be considered merely adjunctive measures in managing sinonasal
      conditions. They are effective and underutilized. Some of the persisting
      unanswered questions will only be answered by further research.

PMID- 14712113
TI  - Chronic rhinosinusitis and eosinophils: do macrolides have an effect?
AB  - PURPOSE OF REVIEW: Long-term, low-dose macrolide therapy is effective in the
      treatment of chronic airway inflammation. It is believed that macrolide
      antibiotics produce this benefit through an antiinflammatory effect that is
      separate from their antibiotic effect. Eosinophils are key mediators in the
      inflammation seen in chronic rhinosinusitis. This review discusses the effect of
      macrolides on eosinophilic inflammation. RECENT FINDINGS: In vitro studies
      recently have suggested that macrolides increase eosinophil apoptosis and reduce
      production of eosinophil chemotactic cytokines and adhesion molecules. In vivo
      studies have shown a reduction in eosinophil count and activity in asthma and
      chronic rhinosinusitis. Clinical response to macrolide treatment is thought to be
      less likely in patients with atopy. SUMMARY: In contrast to the evidence
      supporting the effect of macrolides on neutrophilic inflammation, there are
      limited data to suggest an influence on eosinophilic inflammation. For this
      reason, patients with prominent eosinophilic inflammation may in the future be
      identified as being less likely to respond to treatment. Further in vitro and
      clinical studies are required to investigate this subject.

PMID- 14712114
TI  - Chronic sinusitis and gastroesophageal reflux: are they related?
AB  - PURPOSE OF REVIEW: Gastroesophageal reflux has been implicated in many disorders
      affecting the upper airway over the past three decades. This article reviews the
      recent literature regarding the relationship of chronic rhinosinusitis to
      gastroesophageal reflux. RECENT FINDINGS: Recent studies have demonstrated that
      patients with chronic rhinosinusitis have an increased prevalence of
      gastroesophageal reflux. In addition, many patients (especially children) have
      had improvement in their chronic sinonasal symptoms after therapeutic trials of
      antireflux therapy. SUMMARY: It is possible that gastroesophageal reflux plays a
      role in some patients with chronic rhinosinusitis; thus, evaluation and treatment
      should be considered in this patient population.

PMID- 14712115
TI  - Advantages and disadvantages of topical packing in endoscopic sinus surgery.
AB  - PURPOSE OF REVIEW: Practices regarding the use of nasal packing after endoscopic
      sinus surgery vary widely among surgeons. Recent trends have included the use of
      various topical, absorbable agents. The purpose of this review is to clarify the
      rationale for the selection of these products. RECENT FINDINGS: Although many of
      these materials have proven to be effective as hemostats, data are conflicting
      regarding their effect on mucosal healing. Studies in both humans and animals
      have raised the concern that these agents may be associated with increased scar
      tissue formation. SUMMARY: The exact roles for the various available materials
      are yet to be established. The primary advantage is that they do not require
      removal, which may improve patient comfort. Currently, however, it does not
      appear that the use of topical absorbable packing is a substitute for routine
      postoperative debridement.

PMID- 14712116
TI  - Chronic sinusitis: symptoms versus CT scan findings.
AB  - PURPOSE OF REVIEW: The association between symptoms of chronic rhinosinusitis and
      findings on a sinus CT scan remains controversial. Although the 1997 Task Force
      on Rhinosinusitis definition of chronic rhinosinusitis includes only symptoms and
      signs, many clinicians use CT scans for diagnosis and assessment of disease
      severity. RECENT FINDINGS: Two prospective studies evaluated associations between
      symptoms and CT scan findings. One study compared the diagnosis of chronic
      sinusitis with findings using a validated CT staging system; the CT findings were
      poorly predictive of the presence or absence of chronic sinusitis. The other
      study used a nonvalidated assessment of symptoms and several measurements from CT
      scans and identified a few significant associations. SUMMARY: There are few
      recent studies explicitly addressing symptom severity and CT scan findings in
      chronic sinusitis. Most studies conclude that there is little correlation between
      CT findings and symptoms but that both are important in the evaluation of
      sinusitis.

PMID- 14712117
TI  - Current value of nasal nitric oxide measurement in rhinology.
AB  - PURPOSE OF REVIEW: Since the first description of nitric oxide in the exhaled
      breath of humans by Gustafsson et al., there has been enormous interest in the
      study of nitric oxide and its role in the nose and paranasal sinuses. The aim of
      this review is to present the current knowledge about nasal NO: its physiology,
      novel methods of detection and measurement, and implications in sinonasal
      disease, focusing on the recent data from the literature. RECENT FINDINGS: Nitric
      oxide production is known to be produced in the nose at the apical tip of the
      ciliated respiratory mucosa. A new study has localized nitric oxide production in
      the pericytes and osteocytes of nasal turbinates. Studies have also discovered
      the efficacy of offline measurement techniques showing high correlation between
      standard online measurements with offline techniques. In an interesting study
      examining the influence of maxillary ostium size and nasal nitric oxide levels,
      decreased nitric oxide levels found with larger size ostia may eventually
      influence our approach to sinus surgery. SUMMARY: Nasal nitric oxide has been an
      ever-increasing topic of interest to both the allergist and the head and neck
      surgeon. The recent advances in the study of nasal nitric oxide as it relates to
      sinonasal disease and nasal physiology are discussed and important new findings
      are highlighted.

PMID- 14712118
TI  - Minimally invasive sinus technique: what is it? Should we consider it?
AB  - PURPOSE OF REVIEW: To understand the theory and application of the surgical model
      for endoscopic sinus surgery termed minimally invasive sinus technique (MIST). In
      simple terms: What is MIST? When should we use it? Does it work? RECENT FINDINGS:
      Several recent publications have addressed the efficacy of MIST. Using reliable
      outcome instruments and a 23-month follow-up period, results following MIST were
      found to equal or surpass those following functional endoscopic sinus surgery
      (FESS). These results were valid across the spectrum of disease severity. Other
      reports address the reduced revision rate (compared with FESS) following initial
      intervention with MIST, the potential to markedly reduce the rate of intranasal
      synechiae, and the reduction in immediate postoperative morbidity. SUMMARY: The
      authors believe that MIST should be considered as the initial surgical
      intervention offered to patients undergoing surgery for the treatment of chronic
      rhinosinusitis.

PMID- 14712120
TI  - Nasal endoscopy and control of epistaxis.
AB  - PURPOSE OF REVIEW: This review is designed to update the reader on the current
      state of nasal endoscopy in the control of epistaxis. Recent articles are
      reviewed and demonstrate recent developments and results. RECENT FINDINGS: The
      use of endoscopy for control of anterior and posterior epistaxis is beneficial,
      with less morbidity then external procedures or Caldwell Luc approaches.
      Postoperative endoscopic sinus surgery epistaxis is easily treated with
      endoscopic visualization. Epistaxis secondary to tumors can be controlled via an
      endoscopic approach. Patients with Osler-Weber-Rendu disease (hereditary
      hemorrhagic telangiectasia) can have more selective laser control of
      telangiectasia using endoscopic technique. Endoscopic septodermoplasty is
      straight-forward and avoids external incisions. Following a protocol for control
      of hemorrhage from an injured carotid artery during endoscopic sinus surgery,
      patients can survive with good function. SUMMARY: Endoscopic visualization and
      techniques are the state of the art for surgical control of epistaxis.
      Alternatives are embolization or external/Caldwell-Luc approaches.

PMID- 14712119
TI  - Disadvantages of minimal techniques for surgical management of chronic
      rhinosinusitis.
AB  - PURPOSE OF REVIEW: Controversy exists over the best surgical treatment for
      chronic rhinosinusitis. Minimally invasive sinus technique is a conservative
      approach in which simple ventilation of the lower sinuses is thought to cure even
      severe pathologic disease. Recent articles have suggested short-term subjective
      efficacy. Before this procedure is validated, we must compare it with the current
      gold standard: functional endoscopic sinus surgery. RECENT FINDINGS: Functional
      endoscopic sinus surgery has been the standard surgical technique for many years
      and has demonstrated true short- and long-term subjective and objective efficacy.
      With improved understanding of the pathogenesis of chronic rhinosinusitis, it
      appears that much of its success lies in its ability to fully remove diseased
      bony partitions and to remove areas of chronic inflammation and assist in the
      medical management of chronic rhinosinusitis. SUMMARY: Given our current
      knowledge of chronic rhinosinusitis, functional endoscopic sinus surgery is the
      approach that has shown great success and makes the most sense when surgery is
      truly required in the management of this disease process.

PMID- 14712121
TI  - Management of frontal sinus fractures.
AB  - PURPOSE OF REVIEW: This review summarizes the contemporary management of frontal
      sinus fractures. RECENT FINDINGS: Recent additions to the armamentarium of the
      facial trauma surgeon include bioresorbable plates and screws, and attempts to
      use endoscopic techniques when feasible. SUMMARY: The basic principles of frontal
      sinus fracture management remain the same. New approaches and new instruments
      help make repair easier, safer, and more cosmetically acceptable.

PMID- 14712122
TI  - Revision endoscopic frontal sinus surgery.
AB  - PURPOSE OF REVIEW: Recurrent or persistent frontal sinus disease after endoscopic
      sinus surgery poses formidable challenges owing to the frontal sinus outflow
      tract's complex variable anatomy, close proximity to vital structures, and
      predilection for scarring and stenosis. Frontal sinus obliteration used to be the
      preferred technique of most sinus surgeons for addressing difficult frontal sinus
      disease; however, several effective endoscopic techniques exist as excellent
      alternative procedures for addressing this difficult clinical problem. RECENT
      FINDINGS: Several endoscopic techniques have been described for addressing these
      problems including endoscopic frontal sinusotomy, the frontal sinus rescue
      procedure, endoscopic transseptal frontal sinusotomy, and the modified Lothrop
      procedure. Advances in treating recurrent frontal sinus disease have included
      recent articles reviewing the long-term outcomes of some of these techniques, the
      prevalence of frontal sinus cells, the optimization of medical management, and
      the spectrum of postoperative debridement regimens. SUMMARY: When used in the
      appropriate setting, these less invasive revision endoscopic techniques provide
      excellent results with low morbidity and several advantages. This article reviews
      recent developments in the treatment of recurrent or persistent frontal sinus
      disease including incorporation of these techniques.

PMID- 14712123
TI  - Surgical treatment of the inferior turbinate: new techniques.
AB  - PURPOSE OF REVIEW: Nasal obstruction causing airway resistance is often a result
      of structural abnormalities. Frequently, turbinate reduction procedures have been
      used after failure of medical management to address enlarged inferior turbinates,
      which potentially cause functional narrowing at the nasal valve. Controversy
      still exists as to the best or most appropriate method for surgical reduction of
      the inferior turbinate. The multitude of approaches available to the rhinologist
      is a testament to the lack of a single established method. RECENT FINDINGS: This
      paper highlights recently published literature regarding current popular and
      cutting-edge techniques. There is a trend toward less invasive techniques that
      can potentially be performed in the clinic setting, rather than in the operating
      room. In addition, surgical turbinate intervention demonstrates benefit in
      controlling symptoms of allergic rhinitis other than nasal obstruction. SUMMARY:
      Surgical reduction of the inferior turbinate can be performed using a variety of
      techniques. When analyzing different methods, emphasis on efficacy, function
      preservation, and avoidance of complications is paramount.

PMID- 14712124
TI  - Contrast dynamics during CT pulmonary angiogram: analysis of an inspiration
      associated artifact.
AB  - OBJECTIVE: Several artifacts have been observed during contrast-enhanced CT of
      the pulmonary arteries. We describe a physiological artifact caused by a
      transient interruption of the contrast column in the pulmonary arteries
      associated with inspiration immediately prior to imaging. This results from a
      variable inflow of unopacified blood from the inferior vena cava (IVC). MATERIALS
      AND METHODS: From 327 consecutive pulmonary CT-angiograms, all performed on a
      single detector scanner at 3 mm collimation (1.5 mm incremental reconstruction),
      50 positive studies, 46 indeterminate studies, and 33 negative studies (129
      exams) were retrospectively reviewed by a blinded observer to determine the
      frequency of the described contrast interruption, its severity (mild, moderate,
      or severe), and its possible contribution to misinterpretation of studies. The
      numerical change in Hounsfield units was assigned within the right ventricular
      chamber for each examination to correlate with the subjective evaluation of
      severity. Statistical significance was determined with P = 0.05%. RESULTS: The
      artifact was present in 48 (37.2%) of the 129 evaluated studies. It was greater
      in frequency (50.0%) with the negative studies. The presence was 25% with
      positive studies and 36.7% with indeterminate exams. The interruption was more
      often mild (<100 HU change) in severity (45.8%). Three (6.6%) definite false
      positives were detected where the misinterpretation was directly attributed to
      the artifact. Three (6.6%) other examinations called positive were also directly
      related to the interrupted contrast column. However, since no further pulmonary
      vascular evaluation was performed, these examinations can only be considered
      indeterminate. Two of the latter 3 studies demonstrated a severe (>150 HU change)
      and the other study demonstrated a moderate (100-150 HU) interruption of contrast
      opacification. CONCLUSIONS: During inspiration, there is a variable increase in
      unopacified venous blood from the IVC, briefly diluting the contrast column
      entering from the SVC. This interruption is common, though usually mild in
      severity. However, a short severe interruption of vascular opacification can lead
      to misinterpretation as a pulmonary embolus or contribute to an indeterminate
      examination.

PMID- 14712125
TI  - In vitro evaluation of normal and abnormal lungs with ultra-high-resolution CT.
AB  - Synchrotron radiation microtomography is a new technique with high directionality
      of a synchrotron radiation beam and a high-resolution detector array. In this
      study, we estimated the visualization of the peripheral human lung structure with
      an ultra-high-resolution computed tomography (CT) system, the synchrotron
      radiation CT. The synchrotron radiation CT system uses the bending magnet
      beamline emitted from the 8.0 GeV electron storage ring. Six lung specimens were
      obtained at autopsy: 3 normal, 1 cellular alveolitis, 1 diffuse alveolar damage,
      and 1 pulmonary hemorrhage. Each specimen was cut down to a cylindrical sample
      with 6-mm diameter and 15- to 25-mm height. The synchrotron radiation CT images
      of these lung samples were obtained using the ultra-high-resolution image
      detector system with a charge coupled device (CCD) array detector (1024 x 1024
      pixels with 12 x 12 microm2 pixel size). After that, the sample specimens were
      sliced to 200 microm (micrometer) thickness, and were observed with a
      stereomicroscope and by contact radiography. Finally, approximately 10-microm
      thick microscopic images were obtained and compared with the synchrotron
      radiation CT images. The synchrotron radiation CT could depict the peripheral
      lung including peripheral airways, airspaces, and alveolar walls individually.
      Each finding in the 3 disease processes seen on the synchrotron radiation CT
      images correlated well with the microscopic findings. The synchrotron radiation
      CT allows microtomographic imaging of human lung specimens with ultra high
      spatial resolution (12 microm) on a level approaching that of conventional
      histopathology, without sectioning.

PMID- 14712126
TI  - Application of rational practice and technical advances for optimizing radiation
      dose for chest CT.
AB  - Though clinical benefits of CT exceed the adverse effects of radiation, the
      increasing use of CT has raised a compelling case for reducing radiation
      exposure. This controversy has been compounded by the sheer magnitude of CT
      examinations being performed annually, alleged overuse, and inappropriate
      selection of optimum scanning parameters, all of which expose the patient
      population to increased radiation exposure. Recommended clinical strategies for
      radiation dose optimization include optimization of scanning parameters and
      creating awareness and adopting guidelines for legitimate indications for CT
      scanning to avoid overuse and hence, the associated over-exposure. Whereas
      technological advances have increased the applications of the modality, it is
      also assisting in development of promising techniques to reduce associated
      radiation exposure, while maintaining "optimum image quality" needed to make a
      confident diagnosis. The present pictorial essay describes the fundamentals of CT
      radiation exposure and need for CT radiation dose reduction on the basis of
      documented scanning practices and technological advances.

PMID- 14712127
TI  - Comparison of axial high-resolution CT and thin-section multiplanar reformation
      (MPR) for diagnosis of diseases of the pulmonary parenchyma: preliminary study in
      49 patients.
AB  - PURPOSE: We evaluated the diagnostic utility of coronal multiplanar reformation
      (MPR) images produced by multi-detector row CT in diffuse and focal pulmonary
      parenchymal disease. MATERIALS AND METHODS: A phantom study was conducted
      comparing spatial and low-contrast resolutions of axial high-resolution CT (HRCT)
      and coronal MPR. Non-spiral axial HRCT was performed with 2-mm collimation, and
      spiral CT was performed with 1-mm collimation and 8:1 pitch, from which MPR
      images were produced at 1.9-mm thickness and 5-mm intervals. Forty-nine patients
      were included in the clinical study. Three reviewers independently assessed the
      lesion conspicuity and disease extent on both axial HRCT and coronal MPR images,
      and the diagnostic utility of the coronal images was evaluated. Two reviewers
      subsequently assessed axial and coronal images separately, and the extent of
      abnormalities shown by each was compared. RESULTS: In phantom study, coronal MPR
      images were inferior to axial images but were considered adequate for clinical
      use. In clinical study, the image quality of MPR was regarded as good for
      observation of the lung parenchyma in all cases. The mean percentage of
      abnormalities for which 3 reviewers determined coronal MPR images as superior or
      additional information available was 22.1%, whereas 72.4% was regarded as
      comparable and 5.5% as inferior to axial images. Interobserver agreement was good
      (weighted kappa statistics 0.45-0.61). The extent of abnormality was judged to be
      shown equally on the axial and MPR images with good interobserver agreement
      (kappa statistics 0.63). CONCLUSION: Coronal MPR images may have an additional
      role to axial HRCT images in the clinical interpretation of lung parenchymal
      abnormalities.

PMID- 14712128
TI  - Pitfalls in lung cancer assessment with CT.

PMID- 14712129
TI  - Late reactivation of tuberculosis in an oleothorax.
AB  - The injection of oil into the pleural cavity was a widely used treatment of
      pulmonary tuberculosis until the advent of effective anti-tuberculous therapy.
      Long-term complications of oleothorax can occur when the oil is not removed. The
      authors present an unusual complication of oleothorax, reactivation of
      tuberculosis, 54 years after oil instillation.

PMID- 14712130
TI  - Pulmonary hamartoma: unusual radiologic appearance.
AB  - A pulmonary nodule was incidentally detected in a 50-year-old man during a
      routine health evaluation. High-resolution computed tomography (HRCT) showed that
      the lesion had the appearance of a collection of multiple tiny nodules.
      Histologic examination of the resected specimen revealed a single hamartoma
      resembling a bunch of grapes. Pulmonary alveoli and bronchioles were entrapped
      within the hamartoma with tumor buds appearing in a multicentric manner, thereby
      producing the unusual HRCT findings. Review of chest radiographs taken over the
      previous 20 years indicated that the tumor doubling time was 4968 days.

PMID- 14712131
TI  - Inhalational pulmonary talcosis: high-resolution CT findings in 3 patients.
AB  - We describe the high-resolution CT findings in 3 patients with pulmonary talcosis
      acquired by the inhalation of talc. The predominant abnormalities consisted of
      small centrilobular and subpleural nodules and conglomerated masses containing
      focal areas of high attenuation consistent with talc deposition. All patients
      also had focal ground glass opacities. The abnormalities were diffuse but were
      most severe in the upper and middle lung zones with relative sparing of the lung
      bases.

PMID- 14712132
TI  - Traumatic intrapericardial ascending aortic rupture: CT appearance.
AB  - Ascending aortic injury is seen in only 5% of patients who survive long enough to
      undergo imaging. Emergent aortography is commonly used to confirm and define
      suspected thoracic rupture. We describe a case of ascending aortic rupture at the
      root of the aorta following blunt trauma diagnosed with CT imaging.

PMID- 14712133
TI  - Disseminated pulmonary candidiasis complicating hyperimmunoglobulin E (Job's)
      syndrome.
AB  - Hyperimmunoglobulin E (Job's) syndrome is a rare disease characterized by
      recurrent pneumonia and sinusitis, pneumatoceles, chronic dermatitis, and
      elevated serum levels of immunoglobulin E. In this report, the author presents a
      case of disseminated pulmonary candidiasis in a young man with
      hyperimmunoglobulin E syndrome. His chest radiograph showed reticulonodular
      opacities in both lungs. Computed tomography scans revealed multiple pulmonary
      nodules and hilar and mediastinal enlarged lymph nodes.

PMID- 14712134
TI  - HRCT appearance of systemic mastocytosis involving the lungs.
AB  - Systemic mastocytosis is an uncommon disease of unknown prevalence. Most patients
      clinically present with urticaria pigmentosa. The diagnosis is made by finding
      increased mast cells in the involved tissues. Pulmonary involvement in systemic
      mastocytosis is rare. The chest radiographic findings include reticulonodular
      opacities and lung nodules. We present a case of histologically proven pulmonary
      and skeletal systemic mastocytosis (AKA systemic mast cell disease) associated
      with a hematologic condition, including the high-resolution computed tomographic
      findings of this disorder.

PMID- 14712135
TI  - Congenital pulmonary lymphangiectasia: CT and pathologic findings.
AB  - Congenital pulmonary lymphangiectasia is a rare disease characterized by dilation
      of lymphatic channels without lymphatic proliferation. The disease is seen almost
      exclusively in infancy and early childhood. The authors report 2 cases of
      pulmonary lymphangiectasia. The patients were a 12- and a 25-year-old male who
      presented with progressive dyspnea and hemoptysis. The diagnosis was confirmed by
      open lung biopsy. The radiographic findings consisted of bilateral reticular
      changes, peribronchial cuffing, and bilateral pleural effusions. High-resolution
      CT demonstrated extensive bilateral septal and peribronchovascular interstitial
      thickening, areas of ground-glass attenuation, and bilateral pleural effusions.
      The histologic findings consisted of ectatic and tortuous lymphatic channels in
      the interlobular septa, bronchovascular sheaths, and pleura.

PMID- 14712136
TI  - Granulomatous chest disease following intravesical bacillus Calmette-Guerin
      immunotherapy.
AB  - Bacillus Calmette-Guerin (BCG) is well accepted as an intravesicular method of
      treatment of bladder cancer. Although well tolerated in the majority of patients,
      adverse local and systemic adverse effects of this therapy have been described.
      In particular, lung disease complicating intravesicular use of BCG has been
      reported, producing 5 recognized forms of chest disease: 1) allergic interstitial
      lung disease, 2) miliary infection, 3) empyema, 4) diffuse alveolar damage, and
      5) localized consolidative or cavitary lung disease. We report an asymptomatic
      form of pulmonary disease complicating intravesical BCG therapy, that of
      pulmonary granulomas with mediastinal and hilar lymph node enlargement.

PMID- 14712137
TI  - Bronchioloalveolar carcinoma with fluctuating extent of consolidation on chest
      radiography.
AB  - We report a case of bronchioloalveolar carcinoma that required approximately 1
      year to diagnose due to alternating periods of exacerbation and improvement of
      abnormal opacity on chest radiography. It is important to consider the diagnosis
      of bronchioloalveolar carcinoma when consolidative opacities simulating pneumonia
      show an alternating pattern of worsening and improvement.

PMID- 14712138
TI  - On precision.

PMID- 14712140
TI  - Genetic testing for sale.

PMID- 14712141
TI  - Residential exposure to traffic in California and childhood cancer.
AB  - BACKGROUND: Motor vehicle emissions are a major source of air pollution in
      California. Past studies have suggested that traffic-related exposures can
      increase the risk of childhood cancer, particularly leukemia. METHODS: From
      California's statewide, population-based cancer registry, we identified cancers
      diagnosed in children younger than 5 years of age between 1988 and 1997. We
      matched these cases to California birth certificates. For each case, we randomly
      selected 2 control birth certificates, matched by birth date and sex. For each
      mother's residential address at the time of her child's birth, we calculated road
      density by summing the length of all roads within a 500-foot radius of the
      residence. Traffic density was based on road lengths and vehicle traffic counts
      for highways and major roads. RESULTS: The distributions of road and traffic
      density values were very similar for the 4369 cases and 8730 matched control
      subjects. For all cancer sites combined, the odds ratio (OR) for the highest road
      density exposure category, compared with the lowest, was 0.87 (95% confidence
      interval [CI] = 0.75-1.00). For all sites combined and for leukemia, the ORs were
      also below 1.0 for the highest traffic density exposure category (0.92 for both).
      For central nervous system tumors, the OR was 1.22 (CI = 0.87-1.70). CONCLUSIONS:
      In a large study with good power, we found no increased cancer risk among
      offspring of mothers living in high traffic density areas for all cancer sites or
      leukemia.

PMID- 14712142
TI  - Infant otitis media and the use of secondary heating sources.
AB  - BACKGROUND: This prospective study investigated the association of exposure to
      indoor secondary heating sources with otitis media and recurrent otitis media
      risk in infants. STUDY DESIGN: We enrolled mothers living in nonsmoking
      households and delivering babies between 1993 and 1996 in 12 Connecticut and
      Virginia hospitals. Biweekly telephone interviews during the first year of life
      assessed diagnoses from doctors' office visits and use of secondary home heating
      sources, air conditioner use, and day care. Otitis media episodes separated by
      more than 21 days were considered to be unique episodes. Recurrent otitis media
      was defined as 4 or more episodes of otitis media. Repeated-measures logistic
      regression modeling evaluated the association of kerosene heater, fireplace, or
      wood stove use with otitis media episodes while controlling for potential
      confounders. Logistic regression evaluated the relation of these secondary
      heating sources with recurrent otitis media. RESULTS: None of the secondary
      heating sources were associated with otitis media or with recurrent otitis media.
      Otitis media was associated with day care, the winter heating season, birth in
      the fall, white race, additional children in the home, and a maternal history of
      allergies in multivariate models. Recurrent otitis media was associated with day
      care, birth in the fall, white race, and a maternal history of allergies or
      asthma. CONCLUSION: We found no evidence that the intermittent use of secondary
      home heating sources increases the risk of otitis media or recurrent otitis
      media. This study confirms earlier findings regarding the importance of day care
      with respect to otitis media risk.

PMID- 14712143
TI  - Reproductive effects of male psychologic stress.
AB  - OBJECTIVES: Male psychologic stress can affect semen quality and couple
      fecundability. METHODS: We conducted a prospective study of 430 Danish couples
      who were trying to become pregnant for the first time. In each menstrual cycle,
      both partners filled out a 12-item version of the General Health Questionnaire
      (GHQ-12), an assessment of psychologic stress. A blood sample was drawn from both
      partners. The men collected a semen sample at enrollment and each month during
      follow up. RESULTS: Semen quality was not related to the man's GHQ score in
      either within-subject analyses or between-subject analyses. There were no
      consistent associations between stress and serum concentration of luteinizing
      hormone, follicle-stimulating hormone, inhibin B, testosterone, or estradiol. The
      pregnancy rate was 14% in cycles with an absolute GHQ-12 score in the highest
      quartile, compared with 18% in low-stress cycles. Odds of pregnancy decreased
      moderately with increasing score. The effect was confined to 77 men with a sperm
      density below 20 million/mL (adjusted odds ratio = 0.06; 95% confidence interval
      = 1.01-0.58 for highest distressed quartile vs. lowest distressed quartile in
      this low sperm density group). In within-subject analyses, cycle-specific changes
      in male stress did not change the odds of pregnancy. High absolute score was
      associated with a lower frequency of sexual intercourse, but adjustment for
      frequency had little effect. CONCLUSION: The effect of a man's daily life
      psychologic stress on his semen quality is small or nonexistent. Our results
      indicate an effect of stress only on fecundability, and this only among men with
      low sperm concentration.

PMID- 14712144
TI  - Small-for-gestational-age births in the United States: an age-period-cohort
      analysis.
AB  - BACKGROUND: During the last 2 decades, the rate of low birthweight has increased,
      as has the rate of preterm delivery, among both whites and blacks. Examination of
      causes for these secular trends has focused largely on changes in the
      distributions of maternal age and, less commonly, on birth cohort. Little is
      known as to how age, period, and birth cohort interact on trends in small births
      at term. METHODS: The U.S. natality files were used to assess trends in term
      (>/=37 weeks gestation) small-for-gestational age (SGA) births for 7 5-year
      maternal age groups (15-19 through 45-49 years), 6 delivery periods (1975, 1980,
      1985, 1990, 1995, and 2000), and 12 5-year maternal birth cohorts (1926-1930
      through 1981-1985). SGA births were defined as sex-specific birthweight below the
      10th percentile for gestational age based on 1995 livebirths in the United
      States. Logistic regression models were fit to determine the independent effects
      of age, delivery period, and birth cohort on term SGA trends, separately for
      blacks and whites. RESULTS: Between 1975 and 2000, term SGA births declined by
      23% (from 21% to 16%) among blacks and by 27% (from 12% to 9%) among whites. Term
      SGA births declined with increasing age up to 30-34 years, but increased among
      older women. Within strata of maternal age, the risk also declined with later
      maternal birth cohorts, among both blacks and whites. The strongest influence on
      SGA trends was from maternal age, followed by maternal birth cohort, and lastly
      by delivery period. In general, for any combination of age, period, and birth
      cohort, blacks showed 1.5- to 2-fold higher rates of term SGA than whites.
      CONCLUSIONS: The persistence of strong maternal age effects on risk of term SGA
      births suggests that the effect of age is at least partly the result of biologic
      factors. Term SGA trends were generally consistent for blacks and whites,
      although the magnitude of difference in the risks for combinations of age,
      period, or mother's birth cohort was higher among blacks than whites.

PMID- 14712145
TI  - Particulate air pollution and fetal health: a systematic review of the
      epidemiologic evidence.
AB  - BACKGROUND: Research on the potential impact of air pollution on the health of
      adults and children has grown rapidly over the last decade. Recent studies have
      suggested that air pollution could also be associated with adverse effects on the
      developing fetus. This systematic review evaluates the current level of
      epidemiologic evidence on the association between ambient particulate air
      pollution and fetal health outcomes. We also suggest further research questions.
      METHODS: Using database searches and other approaches, we identified relevant
      publications published between 1966 and 2001 in English. Articles were included
      if they reported original data on birthweight, gestational age at delivery, or
      stillbirth related to directly measured nonaccidental exposure to particulate
      matter. RESULTS: Twelve studies met the inclusion criteria. There was little
      consistency in the evidence linking particulate air pollution and fetal outcomes.
      Many studies had methodologic weaknesses in their design and adjustment for
      confounding factors. Even in well-designed studies, the reported magnitude of the
      effects was small and inconsistently associated with exposure at specific stages
      of pregnancy. CONCLUSIONS: The currently available evidence is compatible with
      either a small adverse effect of particulate air pollution on fetal growth and
      duration of pregnancy or with no effect. Further research should be directed
      toward clarifying and quantifying these possible effects and generating testable
      hypotheses on plausible biologic mechanisms.

PMID- 14712146
TI  - Ambient air pollution and cardiovascular emergency department visits.
AB  - BACKGROUND: Despite evidence supporting an association between ambient air
      pollutants and cardiovascular disease (CVD), the roles of the physicochemical
      components of particulate matter (PM) and copollutants are not fully understood.
      This time-series study examined the relation between ambient air pollution and
      cardiovascular conditions using ambient air quality data and emergency department
      visit data in Atlanta, Georgia, from January 1, 1993, to August 31, 2000.
      METHODS: Outcome data on 4,407,535 emergency department visits were compiled from
      31 hospitals in Atlanta. The air quality data included measurements of criteria
      pollutants for the entire study period, as well as detailed measurements of mass
      concentrations for the fine and coarse fractions of PM and several physical and
      chemical characteristics of PM for the final 25 months of the study. Emergency
      department visits for CVD and for cardiovascular subgroups were assessed in
      relation to daily measures of air pollutants using Poisson generalized linear
      models controlling for long-term temporal trends and meteorologic conditions with
      cubic splines. RESULTS: Using an a priori 3-day moving average in single
      pollutant models, CVD visits were associated with NO2, CO, PM2.5, organic carbon,
      elemental carbon, and oxygenated hydrocarbons. Secondary analyses suggested that
      these associations tended to be strongest with same-day pollution levels.
      CONCLUSIONS: These findings provide evidence for an association between CVD
      visits and several correlated pollutants, including gases, PM2.5, and PM2.5
      components.

PMID- 14712147
TI  - Underestimation of standard errors in multi-site time series studies.
AB  - Multi-site time series studies of the association of air pollution with mortality
      and morbidity have figured prominently in the literature as comprehensive
      approaches for estimating short-term effects of air pollution on health.
      Hierarchical models are generally used to combine site-specific information and
      to estimate pooled air pollution effects while taking into account both within
      site statistical uncertainty and across-site heterogeneity. Within a site,
      characteristics of time series data of air pollution and health (small pollution
      effects, missing data, and highly correlated predictors) make the modeling of all
      sources of uncertainty challenging. One potential consequence is underestimation
      of the statistical variance of the site-specific effects to be combined.In this
      paper, we investigate the impact of variance underestimation on the pooled
      relative rate estimate. We focused on two-stage normal-normal hierarchical models
      and on underestimation of the statistical variance at the first stage. By
      mathematical considerations and simulation studies, we found that variance
      underestimation did not affect the pooled estimate substantially. However, the
      pooled estimate was somewhat sensitive to variance underestimation when the
      number of sites was small and underestimation was severe. These simulation
      results are applicable to any two-stage normal-normal hierarchical model for
      combining information of site-specific results (including meta-analyses), and
      they can easily be extended to more general hierarchical formulations. We also
      examined the impact of variance underestimation on the national average relative
      rate estimate from the National Morbidity, Mortality and Air Pollution Study. We
      found that variance underestimation as large as 40% had little effect on the
      national average.

PMID- 14712148
TI  - A practical guide to dose-response analyses and risk assessment in occupational
      epidemiology.
AB  - Dose-response modeling in occupational epidemiology is usually motivated by
      questions of causal inference (eg, is there a monotonic increase of risk with
      increasing exposure?) or risk assessment (eg, how much excess risk exists at any
      given level of exposure?). We focus on several approaches to dose-response in
      occupational cohort studies. Categorical analyses are useful for detecting the
      shape of dose-response. However, they depend on the number and location of
      cutpoints and result in step functions rather than smooth curves. Restricted
      cubic splines and penalized splines are useful parametric techniques that provide
      smooth curves. Although splines can complement categorical analyses, they do not
      provide interpretable parameters. The shapes of these curves will depend on the
      degree of "smoothing" chosen by the analyst. We recommend combining categorical
      analyses and some type of smoother, with the goal of developing a reasonably
      simple parametric model. A simple parametric model should serve as the goal of
      dose-response analyses because (1) most "true" exposure response curves in nature
      may be reasonably simple, (2) a simple parametric model is easily communicated
      and used by others, and (3) a simple parametric model is the best tool for risk
      assessors and regulators seeking to estimate individual excess risks per unit of
      exposure. We discuss these issues and others, including whether the best model is
      always the one that fits the best, reasons to prefer a linear model for risk in
      the low-exposure region when conducting risk assessment, and common methods of
      calculating excess lifetime risk at a given exposure from epidemiologic results
      (eg, from rate ratios). Points are illustrated using data from a study of dioxin
      and cancer.

PMID- 14712149
TI  - The effect of cleaning on dust and the health of office workers: an intervention
      study.
AB  - BACKGROUND: Office employees often experience symptoms that could be related to
      indoor air exposures. METHODS: In an office building, 114 nonsmokers who had
      reported mucosal irritation complaints in a survey were selected to participate
      in a double-blind intervention study. The intervention was carried out in Oslo,
      Norway, during 1998. The offices of the intervention group were given a
      comprehensive cleaning, whereas the offices of the control group got a
      superficial cleaning as a placebo treatment. Dust concentration, health
      complaints, and nasal congestion were recorded before and after intervention or
      placebo. In the intervention group, the mean dust concentration was 67 microg/m3
      before intervention and 50 microg/m3 after cleaning. RESULTS: The intervention
      group reported a reduction in mucosal irritation complaints (a median reduction
      of 1.0 irritation index points on a scale 0-8) compared with no change in the
      control group. The odds ratio for reporting a 2-point reduction of the mucosal
      irritation symptom index was 3.5 (95% confidence interval [CI] = 1.2-9.1) in the
      intervention group compared with the control group. Nasal congestion, measured by
      acoustic rhinometry, was also reduced in the intervention group. The odds ratio
      for reduction in nasal congestion above the 70th percentile was 4.2 (CI = 1.3-11)
      in the intervention group versus the control group. CONCLUSIONS: This
      experimental field trial shows that comprehensive cleaning reduces the airborne
      dust in offices, and also can reduce mucosal symptoms and nasal congestion.

PMID- 14712150
TI  - Obesity in adolescence and adulthood and the risk of adult mortality.
AB  - BACKGROUND There are few long-term follow-up data on the relation between body
      mass index (BMI) in adolescence and in adulthood, and between adolescent BMI and
      adult mortality. The present study explores these relations. METHODS: In
      Norwegian health surveys during 1963-1999, height and weight were measured for
      128,121 persons in a standardized way both in adolescence (age 14-19 years) and
      10 or more years later. Persons were followed for an average of 9.7 years after
      the adult measurement. Cox proportional hazard regression models were used to
      study the association between adolescent and adult BMI and mortality. RESULTS:
      The odds ratio of obesity (BMI >/=30) in adulthood increased steadily with BMI in
      adolescence, from 0.2 for low BMI up to 16 for very high BMI. Very high
      adolescent BMI was associated with 30-40% higher adult mortality compared with
      medium BMI. Adjusting for adult BMI explained most of the association of
      adolescent obesity and mortality, especially among men. Adjustment for smoking
      did not change the results. CONCLUSIONS: Obesity in adolescence tends to persist
      into adulthood. Adolescent obesity is also connected to excess mortality, but
      this excess seems to be explained mostly by obesity in adulthood. High BMI in
      adolescence seems to be predictive of both adult obesity and mortality.

PMID- 14712151
TI  - Does ambient temperature affect foodborne disease?
AB  - BACKGROUND: Foodborne illness is a significant public health issue in most
      countries, including Australia. We examined the association between temperature
      and salmonellosis notifications, and compared these associations for 5 Australian
      cities. METHODS: Log-linear models describing monthly salmonellosis notifications
      in terms of calendar time and monthly average temperatures were fitted over the
      period 1991 to 2001 for each city. We used a negative binomial chance model to
      accommodate overdispersion in the counts. RESULTS: The long-term trend showed an
      increase in salmonellosis notifications in each of the 5 cities. There was a
      positive association between monthly salmonellosis notifications and mean monthly
      temperature of the previous month in every city. Seasonal patterns in
      salmonellosis notifications were fully explained by changes in temperature.
      DISCUSSION: The strength of the association, the consistency across 5 cities, and
      a plausible biologic pathway suggest that higher ambient temperatures are a cause
      of higher salmonellosis notifications. The lag of 1 month suggests that
      temperature might be more influential earlier in the production process rather
      than at the food preparation stage. This knowledge can help to guide policy on
      food preparation and distribution. It also suggests a basis for an early warning
      system for increased risk from salmonellosis, and raises yet another possible
      health problem with global warming.

PMID- 14712152
TI  - Prostatitis as a risk factor for prostate cancer.
AB  - BACKGROUND: The association of infection or inflammation of the prostate with
      prostate cancer has been suggested but not established. This study was undertaken
      to investigate this association. METHODS: Cases were Olmsted County, Minnesota,
      residents with histologically proven prostate cancer diagnosed between January
      1980 and December 1996. Cases (n = 409) were each matched to 2 control subjects
      (n = 803) on age at diagnosis of prostate cancer, residency in Olmsted County,
      and duration of the community medical record. The medical record of each subject
      was reviewed for a history of acute or chronic bacterial prostatitis or chronic
      pelvic pain syndrome (inflammatory type). RESULTS: The relative odds of prostate
      cancer were elevated in men with history of any type of prostatitis (odds ratio
      [OR] = 1.7; 95% confidence interval [CI] = 1.1-2.6) or acute prostatitis (2.5;
      1.3-4.7). The mean time from most recent episode of acute prostatitis to the
      diagnosis of prostate cancer was 12.2 years. After exclusion of men with acute
      prostatitis 2 years before the index date, the relationship was somewhat reduced
      (1.9; 0.9-3.8). Chronic bacterial prostatitis was more weakly associated with
      prostate cancer (1.6; 0.8-3.1), whereas chronic pelvic pain syndrome was not
      associated at all (0.9; 0.4-1.8). CONCLUSIONS: Infection in the form of acute or
      chronic bacterial prostatitis may be associated with prostate cancer. However,
      our data do not provide compelling evidence to support this. As a result of the
      limitations of current methods of assessing chronic prostatitis, biochemical or
      tissue markers of infection or inflammation of the prostate may help clarify
      their role in the pathogenesis of prostate cancer.

PMID- 14712153
TI  - Estrogen replacement therapy and ovarian cancer.
AB  - BACKGROUND: A recent meta-analysis concluded that there was no overall
      association between estrogen replacement therapy (ERT) and risk of epithelial
      ovarian cancer. However, several subsequent studies have suggested that long-term
      ERT could increase ovarian cancer risk. METHODS: We prospectively examined the
      association of ERT with epithelial ovarian cancer among 31,381 postmenopausal
      women in Iowa followed for 15 years. RESULTS: Women who were using ERT at
      baseline had an elevated multivariate-adjusted relative risk of ovarian cancer
      (1.7; 95% confidence interval [CI] = 1.1-2.8) compared with never-users. Risk was
      higher among women who had been using ERT at baseline for more than 5 years (2.5;
      CI = 1.4-4.5). A time-dependent analysis likewise yielded a relative risk of 1.7
      for current ERT use. Former ERT use was not associated with ovarian cancer
      incidence. CONCLUSIONS: Long duration of ERT use after menopause could increase
      the risk of epithelial ovarian cancer.

PMID- 14712154
TI  - Assessment of a one-page questionnaire on long-term recreational physical
      activity.
AB  - BACKGROUND: Physical activity is associated with a reduced risk of several
      chronic diseases. Although there is considerable published research on methods to
      assess current or recent recreational physical activity, there are few short,
      self-administered questionnaires designed to assess long-term physical activity.
      METHODS: We developed a one-page questionnaire to capture data on usual
      recreational physical activity during the preceding 10 years. This questionnaire
      was used in a cohort study of adults age 50 to 75 years residing in western
      Washington state. To examine the measurement characteristics of this
      questionnaire, we compared metabolic equivalent task (MET)-hours derived from
      this short questionnaire to MET-hours estimated from a detailed comparison
      interview in a subsample (n = 217) and to current body mass index (BMI; weight in
      kilograms/height in square meters) in the full sample of 57,811 persons. RESULTS:
      The age- and sex-adjusted partial Pearson correlation coefficient for total
      recreational activity between the 2 instruments was 0.68. In the full cohort, BMI
      was inversely correlated with physical activity as assessed by the one-page
      questionnaire (r = -0.22). CONCLUSIONS: This short questionnaire measures long
      term physical activity at a level of precision appropriate to the examination of
      associations in studies of physical activity and disease.

PMID- 14712155
TI  - Job strain and male fertility.
AB  - BACKGROUND: Job strain, defined as high job demands and low job control, has not
      previously been explored as a possible determinant of male fertility. We
      collected prospective data on job strain among men, and describe the associations
      with semen quality and probability of conceiving a clinical pregnancy during a
      menstrual cycle. METHODS: Danish couples (N = 399) who were trying to become
      pregnant for the first time were followed for up to 6 menstrual periods. All men
      collected semen samples, and a blood sample was drawn from both partners. Job
      demand and job control were measured by a self-administered questionnaire at
      entry, and in each cycle the participants recorded changes in job control or job
      demand during the previous 30 days. RESULTS: In adjusted analyses, no
      associations were found between any semen characteristic or sexual hormones and
      any job strain variable. The odds for pregnancy were not associated with job
      strain. CONCLUSIONS: Psychologic job strain encountered in normal jobs in Denmark
      does not seem to affect male reproductive function.

PMID- 14712156
TI  - A conversation with Jack Schull. Interview by Lowell E. Sever.

PMID- 14712157
TI  - Interpreting authorship order and corresponding authorship.

PMID- 14712158
TI  - Ischemic stroke and temperature decrease.

PMID- 14712159
TI  - Effects of ankle joint effusion on lower leg function.
AB  - BACKGROUND: Inversion ankle sprains are among the most frequently encountered
      injuries in and outside of sport. Altered feedback from joint damage and/or edema
      may negatively affect dynamic stabilization, thereby increasing the patients'
      susceptibility to further injury. In order to understand better how the
      sensorimotor system responds to the presence of ankle edema during a functional
      task, further examination is warranted. OBJECTIVE: To quantify muscle activation
      in the peroneal, tibialis anterior, and soleus musculature as well as to
      determine ankle joint peak torque, peak power, and root mean square (RMS) power
      during a closed kinetic chain activity following artificial ankle effusion.
      DESIGN: Dependent variables were compared within subjects across time intervals
      and between groups. SETTING: All data were collected in the biomechanics
      laboratory. PARTICIPANTS: Subjects were 20 healthy, neurologically sound
      volunteers (age 21.9 +/- 2.1 y, height 174.5 +/- 9.3 cm, mass 79.3 +/- 15.9 kg)
      with no lower extremity injuries. INTERVENTIONS: Subjects were prepared for
      surface electrodes on the peroneus longus (PL), tibialis anterior (TA), soleus
      (Sol), and medial malleolus (ground). Anthropometric measures for the lower
      extremity were recorded for use by the Omnikinetic closed chain dynamometer.
      Measurements were taken prior to ankle effusion (baseline), immediately following
      effusion (post), and again at 30 minutes. MAIN OUTCOME MEASUREMENTS: Testing
      consisted of 6 repetitions at 35% of 1-repetition max and a constant speed of 1.5
      Hz. Separate two-way MANOVAs with repeated measures on time intervals were used
      to detect differences between groups (effusion and control) over time for torque,
      power, and RMS power and for peak and average EMG. RESULTS: An overall time x
      group interaction was detected for EMG (F4,72=3.878; P=0.007) and kinetic
      variables (F6,70=5.55; P=0.0001). Average and peak PL EMG decreased immediately
      following effusion (Sidak's; P=0.048), and average EMG remained depressed 30
      minutes following effusion (Sidak's; P=0.02). Immediately posteffusion, a
      decrease in ankle torque was detected (Sidak's; P=0.007). No differences in TA or
      Sol EMG, power, or RMS power were detected (P>0.05). CONCLUSIONS: Decreases in
      ankle plantarflexion torque and PL EMG indicate that a neuromuscular deficit
      exists in the presence of edema that could increase the susceptibility for
      further ankle injury.

PMID- 14712160
TI  - Popliteal artery entrapment syndrome: anatomic or functional syndrome?
AB  - PURPOSE: The purpose of this retrospective study is to present our clinical
      experience in the diagnosis and treatment of young athletes with popliteal artery
      entrapment syndrome. DESIGN: Retrospective Case Series. METHODS: We report our
      experience with 5 patients with lower leg pain in a population of 2000 athletes
      in whom popliteal artery entrapment diagnosed with the use of duplex
      ultrasonography, computed tomography, digital subtraction angiography or
      conventional arteriography. Posterior surgical approach performed to offer better
      view of the anatomic structures compressing the popliteal artery. RESULTS: In 4
      patients in whom compression had not yet damaged the arterial wall, no anatomical
      abnormalities found within the popliteal fossa during surgical exploration.
      Hypertrophy of gastrocnemius muscle was the only finding. In the fifth patient an
      anatomical abnormality found in which the artery following the classic aberrant
      course, looped medially to and then beneath the medial head of gastrocnemius. All
      patients recovered completely. CONCLUSIONS: We conclude that physicians who
      encounter athletes with progressive lower leg pain should consider functional
      popliteal artery entrapment surgery, which can prevent the disease's progression.
      We discuss clinical symptoms of the syndrome, radiological and ultrasonographical
      findings, and diagnostic criteria. Early diagnosis is of great importance in
      order to avoid vascular complications, and aid in athletes' early rehabilitation.

PMID- 14712161
TI  - Unreported concussion in high school football players: implications for
      prevention.
AB  - OBJECTIVE: To investigate the frequency of unreported concussion and estimate
      more accurately the overall rate of concussion in high school football players.
      DESIGN: Retrospective, confidential survey completed by all subjects at the end
      of the football season. SETTING AND PARTICIPANTS: A total of 1,532 varsity
      football players from 20 high schools in the Milwaukee, Wisconsin, area were
      surveyed. MAIN OUTCOME MEASUREMENTS: The structured survey assessed (1) number of
      concussions before the current season, (2) number of concussions sustained during
      the current season, (3) whether concussion during the current season was
      reported, (4) to whom concussion was reported, and (5) reasons for not reporting
      concussion. RESULTS: Of respondents, 29.9% reported a previous history of
      concussion, and 15.3% reported sustaining a concussion during the current
      football season; of those, 47.3% reported their injury. Concussions were reported
      most frequently to a certified athletic trainer (76.7% of reported injuries). The
      most common reasons for concussion not being reported included a player not
      thinking the injury was serious enough to warrant medical attention (66.4% of
      unreported injuries), motivation not to be withheld from competition (41.0%), and
      lack of awareness of probable concussion (36.1%). CONCLUSIONS: These findings
      reflect a higher prevalence of concussion in high school football players than
      previously reported in the literature. The ultimate concern associated with
      unreported concussion is an athlete's increased risk of cumulative or
      catastrophic effects from recurrent injury. Future prevention initiatives should
      focus on education to improve athlete awareness of the signs of concussion and
      potential risks of unreported injury.

PMID- 14712162
TI  - Sports-related and gender differences on neuropsychological measures of frontal
      lobe functioning.
AB  - OBJECTIVE: To determine similarities and differences in the performance of female
      and male athletes on neuropsychological measures of frontal lobe functioning.
      DESIGN: A cross-sectional study of male and female college-aged athletes involved
      in one of the following sports: hockey, basketball, softball, lacrosse, soccer,
      swimming, and track. SETTING: Division III college. PARTICIPANTS: A total of 262
      athletes (male, n=157; female, n=105) participated in the study. MAIN OUTCOME
      MEASURES: Controlled Oral Word Association (letters F, A, S), Cognitive
      Assessment System (Planned Codes, Planned Connections, Number Detection), and
      WAIS-R-NI Vocabulary were administered to all athletes. RESULTS: MANCOVA was
      performed with gender and sport as fixed factors. Female athletes displayed
      faster and more accurate performance on perceptual-motor tasks (P<0.01) and on
      one condition of a verbal fluency task (P<0.01) compared with male athletes. Male
      hockey athletes showed superior perceptual-motor speed and accuracy (P<0.01)
      compared with male athletes in the track/swimming group. Evaluators were naive to
      athletes' gender and sport. CONCLUSION: Gender- and sport-specific performances
      on perceptual-motor and verbal fluency tasks were found. Adding cognitive
      components to base functions eliminates gender- and sports-related distinctions,
      suggesting that existing differences are related to basic, fundamental skills,
      which are inherent and practiced within the respective sport. Understanding the
      differences and similarities across sports and gender on various neurocognitive
      measures is relevant for determining group differences in studies examining the
      consequences of mild traumatic brain injury among athletes.

PMID- 14712163
TI  - Prevalence of eating disorders in elite athletes is higher than in the general
      population.
AB  - OBJECTIVE: The objectives of the study were to examine the prevalence of anorexia
      nervosa (AN), bulimia nervosa (BN), anorexia athletica (AA), and eating disorders
      not otherwise specified (ED-NOS) in both male and female Norwegian elite athletes
      and a representative sample from the general Norwegian population. DESIGN: A 2
      step study including self-reported questionnaire and clinical interview.
      SETTING/PARTICIPANTS: The entire population of Norwegian male and female elite
      athletes (n=1620) and controls (n=1696) was evaluated for the presence of eating
      disorders (EDs). MAIN OUTCOME MEASUREMENT: Based on the results of the
      questionnaire, all athletes and controls classified as at risk for EDs, and a
      representative sample of athletes and controls classified as healthy participated
      in the clinical part of the study to determine the number of subjects meeting the
      Diagnostic and Statistical Manual of Mental Disorders-IV criteria for EDs.
      RESULTS: More athletes (13.5%) than controls (4.6%; P<0.001) had subclinical or
      clinical EDs. The prevalence of EDs among male athletes was greater in
      antigravitation sports (22%) than in ball game (5%) and endurance sports (9%;
      P<0.05). The prevalence of EDs among female athletes competing in aesthetic
      sports (42%) was higher than that observed in endurance (24%), technical (17%),
      and ball game sports (16%). CONCLUSIONS: The prevalence of EDs is higher in
      athletes than in controls, higher in female athletes than in male athletes, and
      more common among those competing in leanness-dependent and weight-dependent
      sports than in other sports. A collaborative effort among coaches, athletic
      trainers, parents, physicians, and athletes is optimal for recognizing,
      preventing, and treating EDs in athletes.

PMID- 14712164
TI  - Acute effects of premeal versus postmeal exercise on postprandial
      hypertriglyceridemia.
AB  - OBJECTIVE: The objective of this study was to examine the effects of the timing
      of exercise relative to the consumption of a fat-rich meal (81% fat) on
      postprandial hypertriglyceridemia. DESIGN: A single bout of exercise was either
      completed 30 minutes before the fat meal (EM trial) or initiated 90 minutes after
      the fat meal (ME trial). A third trial, fat meal only, served as a control (CON
      trial). The trials performed in a random order, and venous blood samples were
      drawn before and 1.5, 3.5, 5.5, and 7.5 hours after the meal for the
      determination of triglycerides, glycerol, insulin, glucose, and free fatty acids.
      PARTICIPANTS: Ten untrained healthy males 25.2 +/- 0.9 years old (mean +/- SE)
      with maximal oxygen uptake (VO2max) of 46.6 +/- 3.0 mL.kg(-1).min(-1).
      INTERVENTION: Walking exercise performed at 50% VO2max for 90 minutes. MAIN
      OUTCOME MEASURE: Postprandial hypertriglyceridemia, which was quantified by
      calculating the area under the triglycerides curve over the 7.5-hour postprandial
      period. RESULTS: The mean incremental area under the curve (total area adjusted
      to baseline) describing postprandial hypertriglyceridemia was lower both in the
      EM trial (3.16 +/- 0.99 mmol.L(-1).8 h) and in the ME trial (2.96 +/- 0.69
      mmol.L(-1).8 h) compared with CON trial (6.18 +/- 1.10 mmol.L(-1).8 h; P<0.05).
      The corresponding areas under the curve describing the postprandial insulinemia
      were not different between trials (ME: 38.56 +/- 8.36 uIU.mL(-1).8 h; EM: 21.65
      +/- 3.80 uIU.mL(-1).8 h; CON: 25.06 +/- 5.15 uIU.mL(-1).8 h; P>0.05). CONCLUSION:
      A single bout of moderate intensity exercise decreases postprandial
      hypertriglyceridemia irrespective of the timing of the exercise relative to a
      high-fat meal.

PMID- 14712165
TI  - The practical management of Achilles tendinopathy.

PMID- 14712166
TI  - Miyoshi myopathy--an unusual cause of calf pain and tightness.

PMID- 14712167
TI  - Guillain-Barre syndrome in a collegiate football player.

PMID- 14712168
TI  - From neuroses to neuropsychiatry: replacing adjectives with science in the study
      of personality disorders.

PMID- 14712169
TI  - Refining the approaches to personality disorders.

PMID- 14712170
TI  - Neurobiologic function and temperament in subjects with personality disorders.
AB  - BACKGROUND: Personality traits have been hypothesized to involve specific
      neurotransmitter systems. In order to test this model, the relationship between
      the responses to serotonergic and noradrenergic probes, central cerebrospinal
      fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional
      Personality Questionnaire (TPQ) were evaluated in a cohort of personality
      disorder subjects. METHODS: A total of 142 patients meeting at least one
      personality disorder (meeting Diagnostic and Statistical Manual of Mental
      Disorders, Third Edition-Revised criteria) participated in these studies. The
      prolactin response to fenfluramine (a measure of serotonin function) was obtained
      for 110 subjects; growth hormone response to clonidine (a measure of
      noradrenergic function) was obtained for 77 subjects, while homovanillic acid
      (HVA) at baseline, an index of dopaminergic function, was available for 103
      subjects. Measures of central neurotransmitter function (dopaminergic,
      serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4
      hydroxyphenylglycol, respectively) were available for 36 subjects. Separate
      regression analyses utilizing each of the hypothesized associations, where the
      TPQ total scores were used as the dependent measures and the biologic indices
      were the independent measures were conducted. Exploratory correlational analyses
      between these biologic measures and the four dimensions of the TPQ (and its
      subscales) were also conducted. (Correlations are reported if they would remain
      significant at P<.01 level after Bonferroni correction for multiple comparisons
      across the six neuroendocrine measures). RESULTS: In the regression analyses,
      there was a trend association between CSF and plasma HVA in predicting novelty
      seeking (P<.07). No other significant associations were found in the other three
      measures. Regarding the individual correlational analyses, the persistence scale
      of the TPQ was significantly positively correlated with the growth hormone
      response to clonidine (r=.30, P<.008). The sentimentality subscale (reward
      dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45,
      P<.001), while the attachment subscale (also reward dependence) was correlated
      with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002). CONCLUSION: Limited
      support was provided for a relationship between monoamines, particularly dopamine
      and novelty-seeking as well as norepinephrine and reward dependence but other
      hypothesized relationships were not supported by these measures.

PMID- 14712171
TI  - Norepinephrine function in personality disorder: plasma free MHPG correlates
      inversely with life history of aggression.
AB  - OBJECTIVE: Clinical and pre-clinical data suggest the possibility of a facilitory
      role for norepinephrine (NE) in impulsive-aggressive behavior. While clinical
      studies have focused on putative central measures of NE activity, few studies
      have been published using peripheral measures. In this study, the relationship
      between plasma free NE metabolite, plasma free 3-methoxy-4-hydroxyphenylglycol
      (pMHPG), and impulsive aggression was explored in subjects with personality
      disorder. METHODS: Subjects were 30 male subjects with personality disorder in
      whom basal plasma free MHPG concentrations were obtained. Aggression was assessed
      using the Life History of Aggression (LHA) assessment and the Buss-Durkee
      Aggression scales; impulsivity was assessed using the Barratt Impulsiveness and
      the Eysenck Personality Questionnaire Impulsivity scales. RESULTS: A significant
      inverse correlation was found between LHA-Aggression and pMHPG in these subjects.
      Correlations with other behavioral measures were not statistically significant.
      pMHPG was significantly lower among subjects with borderline personality disorder
      but not significantly lower after controlling for LHA-Aggression scores.
      CONCLUSION: These data suggest that pMHPG is inversely correlated with life
      history of aggression in subjects with personality disorder and that central
      and/or peripheral NE may play a role in modulating aggressive behavior in these
      subjects.

PMID- 14712172
TI  - Abuse and neglect in childhood: relationship to personality disorder diagnoses.
AB  - BACKGROUND: Childhood history of abuse and neglect has been associated with
      personality disorders and has been observed in subjects with lifetime histories
      of suicidality and self-injury. Most of these findings have been generated from
      inpatient clinical samples. METHODS: This study evaluated self-rated indices of
      sustained childhood abuse and neglect in an outpatient sample of well
      characterized personality disorder subjects (n=182) to determine the relative
      associations of childhood trauma indices to specific personality disorder
      diagnoses or clusters and to lifetime history of suicide attempts or gestures.
      Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide
      attempts. The Childhood Trauma Questionnaire was administered to assess five
      dimensions of childhood trauma exposure (emotional, physical, and sexual abuse,
      and emotional and physical neglect). Logistic regression was employed to evaluate
      salient predictors among the trauma measures for each cluster, personality
      disorder, and history of attempted suicide and self-harm. All analyses controlled
      for gender distribution. RESULTS: Seventy-eight percent of subjects met
      dichotomous criteria for some form of childhood trauma; a majority reported
      emotional abuse and neglect. The dichotomized criterion for global trauma
      severity was predictive of cluster B, borderline, and antisocial personality
      disorder diagnoses. Trauma scores were positively associated with cluster A,
      negatively with cluster C, but were not significantly associated with cluster B
      diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder
      alone was predicted by sexual, physical, and emotional abuse. Within cluster B,
      only antisocial personality disorder showed significant associations with trauma
      scores, with specific prediction by sexual and physical abuse. For borderline
      personality disorder, there were gender interactions for individual predictors,
      with emotional abuse being the only significant trauma predictor, and only in
      men. History of suicide gestures was associated with emotional abuse in the
      entire sample and in women only; self-mutilatory behavior was associated with
      emotional abuse in men. CONCLUSION: These results suggest that childhood
      emotional abuse and neglect are broadly represented among personality disorders,
      and associated with indices of clinical severity among patients with borderline
      personality disorder. Childhood sexual and physical abuse are highlighted as
      predictors of both paranoid and antisocial personality disorders. These results
      help qualify prior observations of the association of childhood sexual abuse with
      borderline personality disorder.

PMID- 14712173
TI  - Relationship of personality to dissociation and childhood trauma in borderline
      personality disorder.
AB  - BACKGROUND: Dissociation is a prominent feature in some individuals with
      borderline personality disorder (BPD), yet our understanding of the meanings and
      implications of prominent dissociation in BPD remains limited. The purpose of
      this study was to investigate the relationship between dissociation and childhood
      trauma in BPD and to explore the relationships of dissociation and trauma to
      various personality features of BPD. METHODS: Twenty BPD subjects and 24 healthy
      comparison subjects of similar age and gender were administered the Dissociative
      Experiences Scale, the Childhood Trauma Questionnaire-short form, the
      Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the
      Relationship Style Questionnaire, and the Schema Questionnaire. RESULTS: The BPD
      group exhibited greater dissociation and childhood trauma, as well as greater
      pathology in most personality variables, compared with the healthy group.
      Dissociation in BPD was not significantly related to total childhood trauma, but
      only to emotional neglect, which accounted for 23% of the variance in
      dissociation scores. CONCLUSION: Within the BPD group, dissociation was
      associated with fearful attachment and immature defenses, while total childhood
      trauma and emotional neglect were associated with overconnection and
      disconnection schemata. This is a preliminary study with a small sample size, yet
      the correlates of dissociation in BPD merit further investigation.

PMID- 14712174
TI  - The role of childhood trauma in differences in affective instability in those
      with personality disorders.
AB  - BACKGROUND: This study examined the relationship of self-reported histories of
      childhood trauma to measures of affective instability in a sample of unmedicated
      outpatients with various personality disorders (n=174). METHODS: Childhood trauma
      was measured by the Childhood Trauma Questionnaire. Affective instability
      comprises at least two dimensions: affective lability, assessed using the
      Affective Lability Scale, and affective intensity, assessed using the Affective
      Intensity Measure. RESULTS: A history of emotional abuse was the only trauma
      variable that significantly correlated with the affect measures in the total
      sample (r=.21-.30). More fine-grained analyses revealed that the relationship of
      emotional abuse and affective instability measures varied as a function of both
      gender and personality disorder type. In subjects with borderline personality
      disorder, the correlation for emotional abuse was greatly attenuated for both
      Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total
      scores. CONCLUSION: This suggests that nontrauma-related factors may be more
      predominant in affective dyscontrol in individuals with borderline personality
      disorder.

PMID- 14712175
TI  - State-specific prevalence of current cigarette smoking among adults--United
      States, 2002.
AB  - Cigarette smoking in the United States causes serious illnesses among an
      estimated 8.6 million persons and approximately 440,000 deaths annually,
      resulting in 157 billion dollars in health-related economic costs. To reduce
      smoking prevalence, morbidity, mortality, and economic impact, state tobacco
      control programs should include interventions to help persons stop smoking. To
      assess the prevalence of current cigarette smoking among adults, attempts to
      quit, and receipt of physician advice to quit during the preceding year, CDC
      analyzed data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS)
      survey. This report summarizes the results of that analysis, which indicated a
      threefold difference in smoking prevalence across the 50 states, the District of
      Columbia (DC), Guam, Puerto Rico, and the U.S. Virgin Islands (range: 9.5%
      32.6%). To support smokers' attempts to quit, states/areas should implement
      comprehensive tobacco-control programs that include interventions to help persons
      stop smoking (e.g., quitlines).

PMID- 14712176
TI  - Bovine spongiform encephalopathy in a dairy cow--Washington state, 2003.
AB  - On December 23, 2003, the U.S. Department of Agriculture (USDA) made a
      preliminary diagnosis of bovine spongiform encephalopathy (BSE) in a single
      "downer" (i.e., nonambulatory disabled) dairy cow in Washington state. On
      December 25, this diagnosis was confirmed by the BSE international reference
      laboratory in Weybridge, England. This report summarizes the findings of the
      initial investigation of this case and describes the public health prevention
      measures adopted by USDA to protect the human food supply. The occurrence of BSE
      in the United States reinforces the need for physicians to be aware of the
      clinical features of variant Creutzfeldt-Jakob disease (vCJD) and to arrange for
      brain autopsies in all decedents with suspected or probable CJD to assess the
      neuropathology of these patients.

PMID- 14712177
TI  - Fatal respiratory diphtheria in a U.S. traveler to Haiti--Pennsylvania, 2003.
AB  - Respiratory diphtheria can be severe or fatal in unvaccinated persons; even with
      appropriate treatment, 5%-10% of patients with diphtheria die. For >50 years,
      vaccination against diphtheria has been recommended for children and adults in
      the United States. Persons who are unvaccinated or vaccinated inadequately can
      contract diphtheria during travel to areas where the disease is endemic, putting
      them and their close contacts at risk for severe illness. This report describes
      fatal respiratory diphtheria in an unvaccinated Pennsylvania resident who had
      visited Haiti, a country where the disease is endemic. The case highlights the
      need for all international travelers to be up-to-date with all recommended
      vaccinations, including a primary series of diphtheria toxoid-containing vaccine.

PMID- 14712178
TI  - Update: influenza-associated deaths reported among children aged <18 years-
      United States, 2003-04 influenza season.
AB  - During the 2003-04 influenza season, CDC has received reports from state health
      departments regarding deaths among children with evidence of influenza virus
      infection. To help investigate these deaths, CDC has requested that all influenza
      associated deaths among children aged <18 years be reported to CDC through state
      and local health departments during the 2003-04 season. This summary is based on
      preliminary data reported from 31 states as of January 6, 2004, and updates a
      previous report published in MMWR.

PMID- 14712179
TI  - Update: influenza activity--United States, December 21, 2003-January 3, 2004.
AB  - The number of states reporting widespread influenza activity decreased during
      December 21, 2003-January 3, 2004. During the latest reporting week, ending
      January 3, health departments in 38 states, the District of Columbia, and New
      York City reported widespread influenza activity. Nine states reported regional
      activity, one state reported local activity, and one state and Guam reported
      sporadic activity. The percentage of outpatient visits for influenza-like illness
      (ILI) decreased in all surveillance regions during the week ending January 3,
      with an overall national percentage of 6.2%. This percentage is above the
      national baseline of 2.5%. The percentage of specimens testing positive for
      influenza also decreased; however, the percentage of deaths attributed to
      pneumonia and influenza (P&I) increased.

PMID- 14712180
TI  - Real-time myocardial contrast echocardiography for pharmacologic stress testing:
      is quantitative estimation of myocardial blood flow reserve necessary?
AB  - BACKGROUND: Little is known about the diagnostic accuracy of quantitative real
      time myocardial contrast echocardiography (MCE) as an adjunct to stress testing.
      This study was performed to evaluate the agreement between MCE and technetium 99m
      sestamibi single photon emission computed tomography (SPECT) for detection of
      perfusion defects and to investigate whether quantitative assessment of
      myocardial perfusion can increase the diagnostic value of MCE. METHODS: MCE was
      performed at rest and during peak adenosine stress in 50 unselected patients
      undergoing SPECT imaging. Concordance between the 2 methods was assessed using
      kappa statistics. MCE images were analyzed quantitatively, measuring peak
      intensity (A) and maximal rise of signal intensity (beta). Myocardial blood flow
      reserve was estimated by calculating the ratios of A(adenosine)/A(baseline) (A
      reserve), beta(adenosine)/beta(baseline) (beta reserve), and A x
      beta(adenosine)/A x beta(baseline) (A x beta reserve). RESULTS: Visual analysis
      of MCE agreed well with SPECT (kappa = 0.67) with sensitivity of 64%, specificity
      of 97%, and overall accuracy of 87%. Quantitative analysis showed that peak
      signal intensity A significantly increased under adenosine stress in SPECT-normal
      segments (2.6 +/- 1.9 vs 3.0 +/- 1.6 dB, P <.0001), tendencially decreased in
      reversible (3.0 +/- 2.0 vs 2.4 +/- 1.2 dB, P =.07) and remained unchanged in
      fixed (0.9 +/- 0.9 vs 0.8 +/- 0.9 dB) defects. beta Increased markedly under
      adenosine in normal segments (0.4 +/- 0.4 vs 1.4 +/- 1.3, P <.0001) but not in
      segments with reversible or fixed defects. Receiver operating characteristic
      showed that beta reserve and A x beta reserve, but not A reserve, are sensitive
      parameters for detecting perfusion defects with areas under the curve of 0.84,
      0.85, and 0.61, respectively. Cut-off values of 1.9 and 2.3, respectively, for
      beta and A x beta reserve yielded sensitivity rates of 79% and 80%, specificity
      rates of 75% and 78%, and overall accuracy rates of 76% and 79%, respectively.
      CONCLUSION: Quantitative estimation of myocardial blood flow reserve by MCE
      parameters corresponds to the evaluation of myocardial perfusion by nuclear
      imaging and can increase the sensitivity but not the overall accuracy of contrast
      echocardiography.

PMID- 14712181
TI  - Harmonic imaging for endocardial visualization and myocardial contrast
      echocardiography during transesophageal echocardiography.
AB  - BACKGROUND: Although harmonic imaging (HI) improves endocardial visualization and
      is necessary for myocardial perfusion imaging, it has yet to be implemented in
      transesophageal echocardiography. Our goal was to determine whether HI
      implemented in a prototype transesophageal echocardiography probe improved
      endocardial visualization and allowed perfusion imaging. METHODS: In 23 patients,
      fundamental and harmonic images were obtained in the transgastric short-axis
      (TSAX) and midesophageal 4-chamber views, and reviewed for endocardial
      visualization by 3 readers blinded to imaging mode. In 14 additional patients,
      perfusion imaging was performed in the TSAX view during contrast infusion.
      RESULTS: HI improved overall endocardial visualization, most noticeably in the
      anterior and lateral segments (P <.004) in the TSAX view, and in the lateral
      segments (P <.01) in the midesophageal 4-chamber view. The salvage rate was 8.3%
      in the TSAX view and 12.6% in the midesophageal 4-chamber view. Myocardial
      perfusion was consistently confirmed in the inferior (86%), posterior (100%), and
      lateral (79%) segments, but rarely in the septal (21%), anteroseptal (0%), and
      anterior (14%) segments. CONCLUSION: Use of HI with transesophageal
      echocardiography improves endorcardial visualization and allows partial
      assessment of myocardial perfusion.

PMID- 14712182
TI  - Prognostic value of contrast stress echocardiography in patients with image
      quality too limited for traditional noncontrast harmonic echocardiography.
AB  - Clinical data and contrast stress echocardiography (CSE) results were analyzed in
      283 patients to establish the prognostic value of CSE for patients with limited
      echocardiogram image quality at baseline. The mean follow-up period was 736 +/-
      337 days. Only 7 patients (2.5%) had nondiagnostic image quality with contrast
      enhancement. During follow-up, 24 cardiac events (8.5%) occurred (5 cardiac
      related deaths, 2 nonfatal myocardial infarction, 17 coronary
      revascularizations). Overall sensitivity, specificity, and positive and negative
      predictive values were 60.9%, 76.8%, 19.7%, and 95.5%, respectively. Kaplan-Meier
      event-free survival was higher for patients with a negative CSE result as
      compared with those with a positive CSE finding (P <.0001). In a multivariate Cox
      proportional hazards model, positive CSE was the strongest predictor of cardiac
      events (risk ratio 3.7; 95% confidence interval 1.6-8.7). CSE can successfully
      predict cardiac events for patients with limited noncontrast echocardiographic
      image quality. A negative CSE result conferred a good prognosis.

PMID- 14712183
TI  - Measurement of coronary flow velocity reserve in the posterior descending
      coronary artery by contrast-enhanced transthoracic Doppler echocardiography.
AB  - BACKGROUND: Although the measurement of coronary flow velocity (CFV) reserve
      (CFVR) in the left anterior descending coronary artery (LAD) by transthoracic
      Doppler echocardiography has been established, its success rate in the posterior
      descending coronary artery (PD) is still limited. OBJECTIVE: This study reports
      the feasibility and diagnostic accuracy of measuring CFVR in the PD by
      transthoracic Doppler echocardiography. METHODS: CFVR in both the distal LAD and
      the PD was measured in 151 consecutive patients before coronary angiography. PD
      flow was investigated under the guidance of a nondirectional Doppler color flow
      map with harmonic imaging in the modified apical 2-chamber view. Intravenous
      contrast agent, Levovist, was injected to enhance the CFV envelope at baseline
      and during hyperemia. RESULTS: CFVR was obtained in 145 patients in the LAD and
      126 patients in the PD (P <.001). The success rate of CFVR measurement in the PD
      was significantly higher in the last 50 patients (88%) than it was in the first
      50 patients (72%) (P <.05). CFVR in the PD was significantly lower for patients
      with significant stenosis of the artery supplying the PD than it was in those
      without stenosis (1.58 +/- 0.59 vs 2.45 +/- 0.72, P <.001). CFVR in the distal
      LAD was 1.40 +/- 0.62 in patients with significant LAD stenosis and 2.45 +/- 0.80
      in those without stenosis (P <.001). If a cut-off value of CFVR < 2 was used,
      sensitivity, specificity, and accuracy for the diagnosis of significant (>50%)
      stenosis of the artery supplying the PD were 84%, 83%, and 83%, respectively,
      whereas for the LAD they were 91%, 75%, and 80%, respectively. CONCLUSIONS:
      Noninvasive measurement of CFVR in the PD could be obtained in the majority of
      unselected patients using a nondirectional Doppler color flow map and contrast
      enhanced harmonic imaging. The diagnostic accuracy of CFVR in the PD is similar
      to that of the LAD and, hence, has a potential clinical use.

PMID- 14712184
TI  - Quantitative assessment of right ventricular function using doppler tissue
      imaging in fetuses with and without heart failure.
AB  - BACKGROUND: Previous reports have established the use of Doppler tissue imaging
      (DTI) for noninvasive assessment of ventricular function, but the technique has
      not been validated for diagnosis of fetal cardiac failure. OBJECTIVE: The purpose
      of this study was to assess right ventricular (RV) function in fetuses with heart
      failure using DTI. METHODS: In all, 43 fetuses (36 control, 7 heart failure) were
      assessed using pulsed Doppler echocardiography combined with DTI. RV peak
      myocardial velocities during early diastole (Ea), atrial contraction, and systole
      were measured; and tricuspid peak velocities during early diastole (E) and atrial
      contraction. The ratio of E/Ea was used as an index of filling pressure were
      measured. From DTI, a Doppler-derived index of combined systolic/diastolic
      myocardial performance (DTI-Tei index) was measured. RESULTS: Compared with
      control fetuses, the mean Ea was significantly lower and the mean E was
      significantly higher in fetuses with heart failure, although these parameters did
      overlap between the 2 groups. The mean RV myocardial wall-motion velocity during
      atrial contraction, ratio of Ea/RV myocardial wall-motion velocity during atrial
      contraction, and RV myocardial wall-motion velocity during systole did not differ
      between the 2 groups. Compared with control fetuses, the mean E/Ea was
      significantly higher (9.71 +/- 0.91 vs 6.20 +/- 0.97; P <.0001) and the mean DTI
      Tei index was significantly greater (0.79 +/- 0.11 vs 0.55 +/- 0.05; P <.0001) in
      fetuses with heart failure. In addition, the DTI-Tei index z score was >2 in all
      fetuses with heart failure. CONCLUSIONS: This study demonstrated a clinically
      important application of DTI-derived tricuspid annular velocities in fetuses with
      heart failure. Although DTI velocities were not sufficiently sensitive to
      identify fetuses with heart failure versus control fetuses, DTI-Tei index and
      E/Ea were useful and sensitive indicators of global RV dysfunction.

PMID- 14712185
TI  - Longitudinal myocardial velocity gradient derived from pulsed Doppler tissue
      imaging in AL amyloidosis: a sensitive indicator of systolic and diastolic
      dysfunction.
AB  - OBJECTIVE: This study was performed to clarify whether the longitudinal
      myocardial velocity gradient could give new insights into the features of
      congestive heart failure in patients with primary amyloidosis. METHODS: A total
      of 33 consecutive patients with biopsy specimen-proven primary amyloidosis were
      examined by pulsed Doppler tissue imaging. RESULTS: In all, 22 had evidence of
      heart involvement, of whom 11 had clinical congestive heart failure. Sample
      volumes were placed on basal and midventricle in the apical 2- and 4-chamber
      views. Peak systolic, and peak early and late diastolic wall-motion velocities
      were measured at each site. Longitudinal myocardial velocity gradients were
      calculated as the difference between basal and midmyocardial velocities. Single
      point analysis of pulsed Doppler tissue imaging could not distinguish any
      difference among groups, whereas the longitudinal myocardial velocity gradients
      in systole and early diastole were significantly impaired in the patients with
      congestive heart failure compared with both the patients without cardiac
      involvement and those with cardiac amyloidosis without congestive heart failure.
      CONCLUSION: Longitudinal myocardial velocity gradient is a sensitive method for
      detecting systolic and diastolic dysfunction in cardiac amyloidosis and is
      superior to single-point analysis Doppler tissue imaging.

PMID- 14712186
TI  - Evaluation of right ventricular dysfunction in patients with cardiac amyloidosis
      using Tei index.
AB  - BACKGROUND: Cardiac amyloidosis is an infiltrative disease causing predominant
      diastolic dysfunction and systolic dysfunction at its advanced stage. Right
      ventricular (RV) dysfunction is an independent predictor of poor prognosis in
      congestive heart failure and cardiomyopathies. However, the assessment of RV
      function is still technically difficult because of the complicated geometry of
      the RV. The recently proposed Tei index, obtained from the cardiac time interval
      analysis, allows noninvasive and quantitative estimation of global ventricular
      function without geometric evaluation. Therefore, this study was designed to
      assess RV function for patients with cardiac amyloidosis. METHODS: Study patients
      consisted of 30 consecutive patients with biopsy specimen-proven cardiac
      amyloidosis and 50 control subjects. Patients were classified as having early or
      advanced stage of cardiac amyloidosis on the basis of mean left ventricular wall
      thickness < 15 mm or >/= 15 mm. Tei index, defined as the sum of isovolumetric
      contraction and relaxation time divided by ejection time, was obtained from
      tricuspid and pulmonary Doppler flow velocity. RESULTS: RV Tei index was
      significantly increased for patients with cardiac amyloidosis (0.54 +/- 0.16 vs
      0.28 +/- 0.05, amyloidosis vs control, P <.001). The incidences of abnormal RV
      isovolumetric contraction time, ejection time, isovolumetric relaxation time, and
      Tei index in all patients with cardiac amyloidosis were 63%, 43%, 73%, and 83%,
      respectively. The same incidences were 50%, 13%, 63%, and 75% in the early stage
      and 68%, 54%, 77%, and 86% in the advanced stage, respectively. CONCLUSION:
      Patients with cardiac amyloidosis frequently have RV dysfunction even in its
      early stage. Tei index allows simple, noninvasive, and nongeometric estimation of
      RV dysfunction in patients with cardiac amyloidosis.

PMID- 14712187
TI  - Influence of hand-carried ultrasound on bedside patient treatment decisions for
      consultative cardiology.
AB  - To test the hypothesis that hand-carried ultrasound (HCU) may influence patient
      treatment on consultative cardiology rounds, 235 patients who were hospitalized
      (aged 65 +/- 10 years) were studied. First, routine treatment decisions regarding
      diagnostic workup and therapy were made from patient history, physical
      examination, 12-lead electrocardiogram, and chart data. Second, a goal-directed
      HCU study was performed in <10 minutes focusing on left ventricular global and
      regional function, wall thickness, and presence of pericardial effusion, followed
      by a reassessment of treatment decisions. HCU data influenced treatment decisions
      in 149 patients (63%); 50% had a change in medical therapy and 22% had a change
      in their diagnostic workup (most with changes in both). In all, 12 patients (5%)
      had an immediate change in the decision for cardiac catheterization or
      pericardiocentesis. Overall agreement for the above findings with subsequent full
      size system echocardiography ranged from 92% to 100% (kappa 0.91-0.96). Goal
      directed HCU has the potential to influence bedside patient treatment decisions
      and expedite health care.

PMID- 14712188
TI  - Community screening for left ventricular hypertrophy in patients with
      hypertension using hand-held echocardiography.
AB  - Left ventricular (LV) hypertrophy (LVH) confers increased cardiovascular risk on
      patients with hypertension. Echocardiography using new hand-held devices might
      allow community-based cost-effective screening for LVH in a targeted hypertensive
      population. Thus, the aim of this study was to test the validity of hand-held
      ultrasound devices to screen for LVH in the community. Accordingly, 189 patients
      with hypertension attending a community-based heart failure screening program
      underwent echocardiography by both hand-held and standard devices by an
      experienced echocardiographer. LVH was defined as LV mass index >/=134 g.m(-2)
      for men and >/=110 g.m(-2) for women using the Devereux-modified American Society
      of Echocardiography cube equation. No significant differences were noted between
      the 2 devices in the measurement of LV wall thickness or LV mass index. Agreement
      for estimation of LVH between the 2 devices was 86% (kappa = 0.63). The
      sensitivity, specificity, and positive and negative predictive values of the hand
      held device for predicting LVH were 72%, 91%, 73%, and 90%, respectively. Thus,
      hand-held echocardiography devices accurately assessed LVH and may be used for
      community-based screening for LVH in targeted patients with hypertension.

PMID- 14712189
TI  - Absent posteroinferior and anterosuperior atrial septal defect rims: Factors
      affecting nonsurgical closure of large secundum defects using the Amplatzer
      occluder.
AB  - Using transesophageal echocardiography, we sought to determine the anatomic
      characteristics of the secundum atrial septal defects (ASDs) that extend into the
      inferior sinus venosus and have no posteroinferior (PI) rim, to determine the
      factors related to potential closure with an Amplatzer occluder. We also sought
      to understand why large secundum ASDs with a PI but without an anterosuperior
      (AS) rim may require special techniques to reorient the left atrial disk before
      deployment of the waist and right atrial disk. We measured the lengths of 5
      separate rims of the circumferences of 76 secundum ASDs, including
      anteroinferior, AS, superior, posterosuperior, and PI rims. We also measured
      anteroposterior and superoinferior defect diameters, total septal lengths, and
      the ratios of defect diameter to total septal length. The atrial depth was
      measured at the axial angle of the delivery sheath in 5 defects with no AS rim
      for which special techniques were required to achieve successful closure. Of 76
      secundum ASDs, 13 (17%) had no PI rim. Each defect extended from the fossa ovalis
      into the inferior sinus venosus. Compared with defects with a PI rim, the factors
      related to potential closure included 100% larger defect diameters, shorter
      posterosuperior rim lengths, larger defect to total septal length ratios, and
      completely flat posterior atrial walls. When the AS rim was absent the factors
      related to the need for special techniques included diameters >/= 22 mm, atrial
      depth < the calculated Amplatzer occluder left atrial disk diameter, rigid
      wire/disk interface, and obligatory left atrial disk orientation more or less
      perpendicular to the atrial septal plane.

PMID- 14712190
TI  - Biatrial aspergillosis in a patient with immunocompetency.
AB  - A 24-year-old man presented with a 24-hour history of pain and numbness in his
      left arm. The patient's clinical presentation of peripheral embolism was
      corroborated by angiography. Echocardiographic study showed masses in both right
      and left atria. Pathologic specimen from the embolus confirmed the diagnosis of
      aspergillosis.

PMID- 14712191
TI  - Anomalous origin of the left coronary artery from the pulmonary artery
      accompanied by mitral valve prolapse and regurgitation: Surgical implication of
      dobutamine stress echocardiography.
AB  - A young woman with bileaflet mitral valve prolapse and anomalous left coronary
      artery arising from the pulmonary artery, accompanied by significant mitral
      regurgitation (MR), underwent dobutamine stress echocardiography to assess the
      effect of anomalous left coronary artery arising from the pulmonary artery on MR
      severity. On the basis of the dobutamine stress echocardiography-induced
      ischemia, which exacerbated the degree of MR, a revascularization operation
      sparing the mitral valve was performed, resulting in significant improvement of
      the MR. We suggest that dobutamine stress echocardiography could be used to
      assess the relative contribution of each syndrome to the pathophysiology of MR,
      directing the surgical procedure.

PMID- 14712192
TI  - Echocardiographic tamponade in severe left ventricular dysfunction: the impact of
      small pericardial effusion and the absence of pulsus paradoxicus.
AB  - Cardiac tamponade is a commonly encountered clinical entity. It is a clinical
      syndrome characterized by elevated filling pressures, pulsus paradoxicus, and
      eventually, hypotension. It occurs as intrapericardial pressure exceeds
      intracardiac pressures altering ventricular filling. Generally tamponade occurs
      with moderate or large accumulations of pericardial fluid that result in an
      increase in pericardial pressure. It is well known that rapid accumulation of
      relatively small volumes of fluid can cause tamponade pathophysiology. We report
      a less well-recognized phenomenon. In the setting of severe left ventricular
      dysfunction, small volumes of pericardial fluid can result in excessive
      intrapericardial pressure and echocardiographic tamponade in the absence of a
      significant pulsus paradoxicus.

PMID- 14712193
TI  - Traumatic type B aortic dissection causing near total occlusion of aortic lumen
      and diagnosed by transthoracic echocardiography: A case report.
AB  - A true dissection of the descending thoracic aorta resulting from blunt chest
      trauma is a relatively rare injury compared with aortic transsection and occurs
      mostly in the region of the aortic isthmus. It is a life-threatening condition
      that requires rapid and accurate diagnosis. In this case, we report a patient
      with Stanford type B aortic dissection caused by decelerating trauma of the chest
      in a motor vehicle accident causing near total occlusion of the aortic lumen. The
      diagnosis was made by transthoracic echocardiography and confirmed by
      aortography.

PMID- 14712194
TI  - Behcet's aortitis and aortic regurgitation: a report of two cases.
AB  - Behcet's disease is a rare systemic vasculitis that may lead to neurologic
      complications and rare manifestations of aortitis and aortic regurgitation. We
      report 2 cases of Behcet's aortitis and aortic regurgitation. The first patient
      presented with acute stroke. Recognition of acute aortitis on echocardiography
      led to the diagnosis of vasculitis as the cause of the cerebral event. This case
      highlights the echocardiographic features of aortic root pathology from acute
      aortitis to subsequent aortic valve perforation. In both cases, severe aortic
      regurgitation necessitated aortic valve replacement. Both were complicated by
      valve dehiscence requiring reoperation, illustrating the postoperative morbidity
      in this inflammatory condition.

PMID- 14712195
TI  - Noncompaction of the ventricular myocardium associated with mitral regurgitation
      and preserved ventricular systolic function.
AB  - Noncompaction of the ventricular myocardium is an embryonic cardiomyopathy that
      is increasingly being recognized. Mitral regurgitation, when present, is usually
      a result of the associated left ventricular systolic dysfunction. We report 4
      patients with noncompaction of the ventricular myocardium in whom ventricular
      systolic function was preserved. Mitral regurgitation was associated with changes
      in the mitral valve leaflets and an abnormal coaptation pattern. This association
      of noncompaction of the ventricular myocardium with mitral regurgitation has not,
      to our knowledge, been reported.

PMID- 14712196
TI  - Left ventricular hypertrabeculation/noncompaction.
AB  - In normal human hearts the left ventricle (LV) has up to 3 prominent
      trabeculations and is, thus, less trabeculated than the right ventricle. Rarely,
      more than 3 prominent trabeculations can be found at autopsy and by various
      imaging techniques in the LV. For this abnormality, different synonyms are used
      such as spongy myocardium, LV noncompaction, and LV hypertrabeculation (LVHT). In
      this review it is stated that: (1) LVHT has a higher prevalence than previously
      thought and the prevalence of LVHT seems to increase with the improvement of
      cardiac imaging; (2) because LVHT is most frequently diagnosed primarily by
      echocardiography, echocardiographers should be aware and trained to recognize
      this abnormality; (3) LVHT is frequently associated with other cardiac and
      extracardiac, particularly neuromuscular, disorders; (4) there are indications
      that the cause of LVHT is usually a genetic one and quite heterogeneous; and (5)
      controversies exist about diagnostic criteria, nomenclature, prognosis, origin,
      pathogenesis, and the necessity to classify LVHT as a distinct entity and
      cardiomyopathy by the World Health Organization.

PMID- 14712197
TI  - Complications after limb salvage surgery.
AB  - Orthopedic oncology patients gain a chance at an active, disease-free life
      through the use of limb salvage surgery. This goal is reached with meticulous
      technique, detailed operative planning, and the use of endoprosthetic
      replacements and/or bone grafting. This article will address the late
      complications of limb salvage surgery, including aseptic loosening, prosthetic
      fracture and dislocation, as well as graft fracture and nonunion.

PMID- 14712198
TI  - Common abnormalities in temporomandibular joint imaging.
AB  - Magnetic resonance imaging has evolved as a prime diagnostic method for soft
      tissue abnormalities of the temporomandibular joint. The most common
      temporomandibular joint abnormalities are internal derangement and
      osteoarthritis, but there are many other reasons for pain and dysfunction that
      are often overlooked. The purpose of this paper is to illustrate several of these
      more unusual and less well-recognized causes for temporomandibular joint pain and
      dysfunction. For example, internal derangement is often seen in asymptomatic
      individuals. Another purpose is to illustrate the difference in magnetic
      resonance imaging of asymptomatic and symptomatic internal derangement.

PMID- 14712199
TI  - Bacillus Calmette-Guerin osteomyelitis in a patient with severe combined
      immunodeficiency: radiologic appearances of extensive dissemination.

PMID- 14712200
TI  - Basal ganglia: anatomy, pathology, and imaging characteristics.
AB  - Several cases of bilateral basal ganglia lesions seen in magnetic resonance
      imaging initiated a review of the anatomy, pathology, and differential diagnoses
      of this region. There are a variety of disease entities that present as
      symmetrical basal ganglia abnormalities. Although these findings may not indicate
      a specific diagnosis, knowledge of the characteristics of diseases that affect
      this area can limit the differential considerations. Clinical information is
      often essential for narrowing the possible pathology that can be found here. The
      purpose of this article is to review the anatomy of the basal ganglia, the
      pathologies, clinical histories, and imaging characteristics that can cause
      bilateral basal ganglia lesions.

PMID- 14712205
TI  - Generating mutations but providing chemosensitivity: the role of O6-methylguanine
      DNA methyltransferase in human cancer.
AB  - O(6)-methylguanine DNA methyltransferase (MGMT) is a key enzyme in the DNA repair
      network. MGMT removes mutagenic and cytotoxic adducts from O(6)-guanine in DNA,
      the preferred point of attack of many carcinogens (i.e. methylnitrosourea) and
      alkylating chemotherapeutic agents (i.e. BCNU, temozolamide, etc.).
      Hypermethylation of the CpG island located in the promoter region of MGMT is
      primarily responsible for the loss of MGMT function in many tumor types. The
      methylation-mediated silencing of MGMT has two consequences for cancer. First,
      tumors with MGMT methylation have a new mutator phenotype characterized by the
      generation of transition point mutations in genes involved in cancer etiology,
      such as the tumor suppressor p53 and the oncogene K-ras. Second, MGMT
      hypermethylation demonstrates the possibility of pharmacoepigenomics: methylated
      tumors are more sensitive to the killing effects of alkylating drugs used in
      chemotherapy. These recent results underscore the importance of MGMT in basic and
      translational cancer research.

PMID- 14712206
TI  - Opposite effects of Ha-Ras and Ki-Ras on radiation-induced apoptosis via
      differential activation of PI3K/Akt and Rac/p38 mitogen-activated protein kinase
      signaling pathways.
AB  - It has been well known that Ras signaling is involved in various cellular
      processes, including proliferation, differentiation, and apoptosis. However,
      distinct cellular functions of Ras isozymes are not fully understood. Here we
      show the opposing roles of Ha-Ras and Ki-Ras genes in the modulation of cell
      sensitivity to ionizing radiation. Overexpression of active isoform of Ha-Ras
      (12V-Ha-Ras) in Rat2 cells increases resistance to the ionizing radiation.
      Constitutive activation of phosphoinositide-3-kinase (PI3K) and Akt is detected
      specifically in 12V-Ha-Ras-overexpressing cells. The specific PI3K inhibitor
      LY294002 inhibits PI3K/Akt signaling and potentiates the radiation-induced
      apoptosis, suggesting that activation of the PI3K/Akt signaling pathway is
      involved in the increased radio-resistance in cells overexpressing 12V-Ha-Ras.
      Overexpression of activated Ki-Ras (12V-Ki-Ras), on the other hand, markedly
      increases radiation sensitivity. The p38 mitogen-activated protein kinase (MAPK)
      activity is selectively enhanced by ionizing radiation in cells overexpressing
      12V-Ki-Ras. The specific p38 MAPK inhibitor, PD169316, or dominant-negative p38
      MAPK decreases radiation-induced cell death. We further show that the mechanism
      that underlies potentiation of cell death in cells overexpressing 12V-Ki-Ras
      involves Bax translocation to the mitochondrial membrane. Elevated Bax
      translocation following ionizing irradiation in 12V-Ki-Ras-overexpressing cells
      is completely inhibited by PD169316 or dominant-negative p38 MAPK. In addition,
      introduction of cells with RacN17, a dominant-negative mutant of Rac, resulted in
      a marked inhibition of radiation-induced Bax translocation and apoptotic cell
      death as well as p38 MAPK activation. Taken together, these findings explain the
      opposite effects of Ha-Ras and Ki-Ras on modulation of radiosensitivity, and
      suggest that differential activation of PI3K/Akt and Rac/p38 MAPK signaling by Ha
      Ras and Ki-Ras may account for the opposing response to the ionizing radiation.
      These data provide an explanation for the diverse biological functions of Ras
      isozymes, and partly accounts for the differential response of transformed cells
      to anticancer treatments.

PMID- 14712207
TI  - P21(WAF1/CIP1) is dispensable for G1 arrest, but indispensable for apoptosis
      induced by sodium butyrate in MCF-7 breast cancer cells.
AB  - Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However,
      its mechanism of action is not totally elucidated. Here, we showed that NaB
      induced cell cycle arrest and apoptosis were associated with an increase of
      P21(waf1/cip1) in MCF-7 breast cancer cells. This increase was more important in
      the nuclei, as revealed by immunofluorescence analysis. Transient transfections
      of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21
      deficient for interaction with PCNA (p21PCNA-), abrogated NaB-induced cell cycle
      arrest. This indicated that cell cycle blockage involved the interaction of
      P21(waf1/cip1) with CDK. However, P21(waf1/cip1) was dispensable, since p21
      antisense did not modify cell cycle arrest. On the other hand, NaB-induced
      apoptosis was abolished by p21 antisense or p21PCNA-. In addition, NaB decreased
      PCNA levels, but increased the association of PCNA with P21(waf1/cip1). These
      results suggested that NaB-induced apoptosis required P21(waf1/cip1) and its
      interaction with PCNA.

PMID- 14712208
TI  - Radiation resistance of human melanoma analysed by retroviral insertional
      mutagenesis reveals a possible role for dopachrome tautomerase.
AB  - While melanomas are resistant to the cytotoxic effects of radiotherapy, little is
      known about the molecular mechanisms underlying this intrinsic resistance. Here,
      we describe the utilization of retroviral insertional mutagenesis to facilitate
      the analysis of genetic changes that are associated with radioresistance in human
      melanoma. A radial growth phase human melanoma cell line, WM35, was infected with
      a replication-defective amphotropic murine retrovirus and subsequently selected
      for X-ray radiation-resistant variants. Several radiation-resistant clones were
      independently isolated and characterized. Interestingly, these clones also
      displayed resistance to ultraviolet radiation and to the chemotherapeutic drug
      cis-diamminedichloroplatinum(II) (CDDP). By Northern and Western analyses, we
      showed that the expression of DOPAchrome tautomerase (DCT), also known as
      tyrosinase-related protein 2 (TYRP2), an enzyme that functions in eumelanin
      synthesis, was significantly elevated in the radiation-resistant clones relative
      to the parental WM35 cells. Moreover, the levels of DCT in a variety of human
      melanoma cell lines correlated with their relative levels of radioresistance and
      the enforced expression of DCT conferred increased resistance to UV(B) treatment.
      An analysis of stress signaling induced by radiation as well other cytotoxic
      stressors showed that resistance associated with DCT overexpression applied
      specifically to treatments that activate the ERK/MAPK pathway. Indeed, DCT
      overexpression in a melanoma cell line resulted in increased ERK activity.
      Moreover, ectopic expression of dominant-active MEK in this melanoma cell line
      conferred UV(B) resistance suggesting that the ERK/MAPK pathway downstream of DCT
      may play a critical role in radiation and drug resistance. Overall, given that
      each gamma- and UV(B)-resistant cell line also exhibited resistance to CDDP and
      that CDDP-resistant clones showed increased resistance to UV(B) irradiation,
      these results suggest a common mechanism underlying radio- and chemoresistance,
      which is mediated by DCT expression.

PMID- 14712210
TI  - Phosphorylation of p53 at serine 37 is important for transcriptional activity and
      regulation in response to DNA damage.
AB  - The p53 tumor suppressor protein plays a critical role in mediating cellular
      response to stress. Upon DNA damage, post-translational modifications stabilize
      and activate this nuclear phosphoprotein. To determine the effect of
      phosphorylation site mutants in the context of the whole p53 protein, we
      performed reporter assays in p53 and MDM2 knockout mouse embryonic fibroblasts
      transfected with full-length p53 constructs. We show that mutation of S37 causes
      a decrease in p53 transcriptional activity compared to wild-type p53. Our data
      further suggest that the dephosphorylation of p53 at S37 is a regulated event
      involving protein phosphatase 2A (PP2A). Coimmunoprecipitation and
      immunofluorescence microscopy studies demonstrate that PP2A and p53 associate
      with one another in vivo following gamma-irradiation. Consistent with these
      observations, phosphorylated S37 accumulates in cell extracts prepared from gamma
      irradiated Molt-4 cells in the presence of okadaic acid. Furthermore, in vitro
      phosphatase assays show that PP2A dephosphorylates p53 at S37. These results
      suggest that dephosphorylation of p53 at S37 plays a role in the transcriptional
      regulation of the p53 protein in response to DNA damage.

PMID- 14712209
TI  - Rapid induction of mitochondrial events and caspase-independent apoptosis in
      Survivin-targeted melanoma cells.
AB  - The inhibitor of apoptosis (IAP) protein Survivin is expressed in most cancers
      and is a key factor in maintaining apoptosis resistance. Although several IAPs
      have been shown to act as direct inhibitors of caspases, the precise
      antiapoptotic function of Survivin remains controversial. To clarify the
      mechanism by which Survivin protects cells, we investigated the kinetics of
      apoptosis and apoptotic events following Survivin inhibition utilizing a melanoma
      cell line harboring a tetracycline-regulated Survivin dominant-negative mutant
      (Survivin-T34A). Blocking Survivin resulted in both caspase activation and
      apoptosis; however, the level of apoptosis was only partially reduced by caspase
      inhibition. Survivin blockade also resulted in mitochondrial events that preceded
      caspase activation, including depolarization and release of cytochrome c and
      Smac/DIABLO. Levels of other IAPs were not altered in Survivin-targeted cells,
      although modest cleavage of XIAP and Livin was observed. The earliest
      proapoptotic event observed in Survivin-targeted cells was nuclear translocation
      of mitochondrial apoptosis-inducing factor (AIF), known to trigger both apoptotic
      mitochondrial events and caspase-independent DNA fragmentation. These findings
      suggest that a key antiapoptotic function of Survivin relates to inhibition of
      mitochondrial and AIF-dependent apoptotic pathways, and its expression in
      melanoma and other cancers likely protects against both caspase-independent and 
      dependent apoptosis.

PMID- 14712211
TI  - The destruction box of human Geminin is critical for proliferation and tumor
      growth in human colon cancer cells.
AB  - A domain-specific disruption was performed on the destruction box sequence of
      endogenous Geminin gene, an inhibitor of the DNA replication initiation complex,
      in a human cancer cell line HCT116 resulting in the formation of a protein that
      was stable in the G1 phase of the cell cycle. Although the total amount of
      Geminin in asynchronous cultures was not elevated, the G1-specific stabilization
      of Geminin, diminished chromatin loading of minichromosome maintenance complex,
      inhibited DNA replication, and resulted in the accumulation of cells in G1. The
      mutated Geminin suppressed in vivo tumorigenicity and in vitro cell growth. Cells
      carrying this mutation failed to support the replication of a plasmid bearing the
      oriP replicator of Epstein-Barr virus. The DNA damage checkpoint pathway was
      activated in the mutated cells with increased levels of p53 protein and its
      target, the p21 protein. All these deficits were rescued by overexpression of
      Cdt1, a replication initiator protein that binds to Geminin. Therefore,
      alteration of the cell cycle-dependent regulation of endogenous Geminin in human
      cells without increasing total protein level inhibits DNA replication and
      suppresses tumor growth.

PMID- 14712212
TI  - Expression and functional significance of CDC25B in human pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer
      related deaths. Deregulation of cell-cycle control is thought to be a crucial
      event in malignant transformation, and CDC25 phosphatases are a family of cyclin
      dependent kinase activators, which act at different points of the cell cycle,
      including G1-S and G2-M transition. Here, we investigated the expression and
      functional significance of CDC25s in PDAC. CDC25B mRNA expression levels in human
      pancreatic tissue samples were analysed by cDNA array, quantitative PCR and
      Northern blotting. Immunohistochemistry was carried out to localize and quantify
      CDC25B expression. Two specific CDC25B inhibitors were utilized to determine the
      functional relevance of CDC25B. By quantitative RT-PCR, CDC25B mRNA was
      overexpressed in pancreatic cancer (7.5-fold) in comparison to the normal
      pancreas. Strong nuclear CDC25B immunoreactivity was present in both pancreatic
      and metastatic cancer samples, and there was a marked increase of the percentage
      of positive cells in primary cancer (48.6+/-16.3%) and metastatic tissues (71.7+/
      3.1%) compared to normal samples (8.3+/-1.8%). Two CDC25B inhibitors reduced the
      growth of pancreatic cancer cell lines, resulting in the accumulation of
      phosphorylated CDC2 and G2/M arrest. These findings demonstrate an important role
      of CDC25B in cell-cycle progression, raising the possibility that inhibition of
      CDC25B may have therapeutic potential in pancreatic cancer.

PMID- 14712213
TI  - DBCCR1 mediates death in cultured bladder tumor cells.
AB  - Chromosome 9, which is often partially or fully reduced to homozygosity in
      bladder cancer cells, harbors several tumor suppressor loci including deleted in
      bladder cancer chromosome region 1 (DBCCR1) at 9q32-33. To study DBCCR1 function,
      stable cell lines, inducible for DBCCR1 expression by tetracycline, were made,
      but the DBCCR1 protein was not expressed at detectable levels. To understand the
      fate of DBCCR1-expressing cells, human bladder tumor cells were transiently
      transfected with an expression vector containing DBCCR1 fused to enhanced green
      fluorescent protein (EGFP). Initially, DBCCR1-EGFP-expressing cells demonstrated
      diffuse cytoplasmic green fluorescence with nuclear exclusion patterns. After
      time, the intensity level of green fluorescence increased and a granular
      distribution of protein became visible in the cells. At this point, cells rounded
      up and detached from the tissue culture dish. Cells transfected with a control
      vector, containing only EGFP, and partial DBCCR1-EGFP fusion constructs did not
      demonstrate this behavior. DBCCR1-mediated cell death in cultured tumor cells was
      independent of caspase-3 activation and did not result in detectable DNA strand
      breaks by TUNEL staining that are hallmarks of the classical apoptotic pathway.

PMID- 14712214
TI  - Human fibroblasts require the Rb family of tumor suppressors, but not p53, for
      PML-induced senescence.
AB  - Cellular senescence is a permanent cell cycle arrest that can be triggered by a
      variety of stresses including short telomeres and activated oncogenes.
      Promyelocytic leukemia protein (PML) is a central component of the senescence
      response, and is able to trigger the process when overexpressed in human diploid
      fibroblasts (HDFs). Senescence induced by PML in HDFs is characterized by a
      modest increase in p53 levels and activity, the accumulation of
      hypophosphorylated Rb and a reduced expression of E2F-dependent genes. To dissect
      the p53 and Rb family requirements for PML-induced senescence, we used the
      oncoproteins E6 and E7 from human papillomavirus type 16. We found that the
      coexpression of E6 and E7 inhibited the growth arrest and senescence induced by
      PML. In addition, these viral oncoproteins blocked the formation of PML bodies
      and excluded both p53 and Rb from PML bodies. Expression of dominant-negative p53
      alone failed to block PML-induced senescence and expression of E6 only delayed
      the process. On the other hand, expression of E7 was sufficient to block PML
      induced senescence, while an E7 mutant unable to bind Rb did not. Together, these
      data indicate that PML-induced senescence engages the Rb tumor-suppressor pathway
      predominantly.

PMID- 14712215
TI  - Peroxisome proliferator-activated receptor-gamma activation inhibits tumor
      progression in non-small-cell lung cancer.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of
      the nuclear hormone receptor superfamily of ligand-activated transcription
      factors and a crucial regulator of cellular differentiation. Differentiation
      inducing and antiproliferative effects of PPAR-gamma suggest that PPAR-gamma
      agonists might be useful as effective anticancer agents. Few studies have
      examined the efficacy of these agonists in animal models of tumorigenesis, and
      their mechanism(s) of action are still not clear. Our studies indicate higher
      PPAR-gamma expression in primary tumors from non-small-cell lung cancer (NSCLC)
      patients when compared to normal surrounding tissue. The expression of PPAR-gamma
      was also observed in several NSCLC lines. The treatment of lung adenocarcinoma
      cells (A549) with troglitazone (Tro), a PPAR-gamma ligand, enhanced PPAR-gamma
      transcriptional activity and induced a dose-dependent inhibition of A549 cell
      growth. The observed growth arrest was predominantly due to the inhibition of
      cell proliferation without significant induction of apoptosis. Cell cycle
      analysis of Tro-treated cells revealed a cell cycle arrest at G(0)/G(1) with
      concomitant downregulation of G(0)/G(1) cyclins D and E. In addition, Tro
      treatment stimulated sustained Erk1/2 activation in A549 cells, suggesting the
      activation of a differentiation-inducing pathway. Furthermore, treatment of A549
      tumor-bearing SCID mice with Tro or Pio inhibited primary tumor growth by 66.7%
      and significantly inhibited the number of spontaneous lung metastatic lesions.
      Collectively, our data demonstrate that activation of PPAR-gamma impedes lung
      tumor progression and suggest that PPAR-gamma ligands may serve as potential
      therapeutic agents for NSCLC.

PMID- 14712216
TI  - H4(D10S170), a gene frequently rearranged with RET in papillary thyroid
      carcinomas: functional characterization.
AB  - Human thyroid papillary carcinomas are characterized by rearrangements of the RET
      protooncogene with a number of heterologous genes, which generate the
      RET/papillary thyroid carcinoma (PTC) oncogenes. One of the most frequent
      variants of these recombination events is the fusion of the intracellular kinase
      encoding domain of RET to the first 101 amino acids of a gene named H4(D10S170).
      We have characterized the H4(D10S170) gene product, showing that it is a
      ubiquitously expressed 55 KDa nuclear and cytosolic protein that is
      phosphorylated following serum stimulation. This phosphorylation was found to
      depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be
      associated to the relocation of H4(D10S170) from the nucleus to the cytosol.
      Overexpression of the H4(D10S170) gene was able to induce apoptosis of thyroid
      follicular epithelial cells; conversely a carboxy-terminal truncated H4(D10S170)
      mutant H4(1-101), corresponding to the portion included in the RET/PTC1
      oncoprotein, behaved as dominant negative on the proapoptotic function and
      nuclear localization of H4(D10S170). Furthermore, conditional expression of the
      H4(D10S170)-dominant negative truncated mutant protected cells from stress
      induced apoptosis. The substitution of serine 244 with alanine abrogated the
      apoptotic function of H4(D10S170). These data suggest that loss of the
      H4(D10S170) gene function might have a role in thyroid carcinogenesis by
      impairing apoptosis.

PMID- 14712217
TI  - Induction of protein growth factor systems in the ovaries of transgenic mice
      overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor
      (LPA2).
AB  - The lipid growth factor lysophosphatidic acid (LPA) is produced by ovarian cancer
      cells in quantities sufficient to attain concentrations of up to 10 microM. An
      autocrine circuit was demonstrated when ovarian cancer cells, but not normal
      ovarian surface epithelial cells, were proven to express LPA(2) (Edg-4) and
      LPA(3) (Edg-7) G protein-coupled receptors for LPA. Human LPA(2) now has been
      expressed transgenically in C57BL/6 mouse ovaries under direction of the alpha
      inhibin large promoter. Human LPA(2) mRNA and protein were detected in all
      transgenic (TG) mouse ovaries at levels far higher than in other tissues and at
      least fivefold higher than in cultured lines of human ovarian cancer cells, with
      the expected sex cord-stromal distribution. Most LPA(2) TG ovaries produced
      significantly higher levels than non-TG ovaries of type A, but not type B,
      vascular endothelial growth factor (VEGF), isomers of VEGF-A, and urokinase-type
      plasminogen activator (uPA). Many LPA(2) TG ovaries had elevated expression of
      VEGF receptors 1 and 2, and a depressed level of type 2 PA inhibitor. Thus, the
      LPA-LPA(2) circuit regulates ovarian cells both directly and through increases in
      protein growth factor systems.

PMID- 14712218
TI  - Insulin-like growth factor-I signaling in human neuroblastoma cells.
AB  - Neuroblastoma is a heterogeneous tumor consisting of N (neuronal) and S (stromal)
      cells. We report that more tumorigenic and motile N cells express higher levels
      of IGF-I receptor (IGF-IR) than less tumorigenic, more adherent S cells. Shc, one
      of the two major docking partners of IGF-IR, is equally expressed in N and S cell
      lines. IGF-I treatment phosphorylates Shc in N cells, but only weakly activates
      Shc in S cells. Expression of the second partner, insulin receptor substrate
      (IRS), is cell type specific. S cells exclusively express IRS-1 that undergoes
      sustained phosphorylation by IGF-I. In contrast, N cells express IRS-2 that is
      transiently phosphorylated by IGF-I. Downstream of IRS-2 and Shc, IGF-I treatment
      results in strong activation of Akt and MAPK in N cells and activation of both
      pathways is required for IGF-I-mediated differentiation. Only IGF-IR activation
      of phosphatidylinositol-3 kinase is required for tumor edge ruffling in N and S
      cells, with stimulation of focal adhesion kinase (FAK) and paxillin. This
      detailed understanding of the 'biochemical signature' of N and S cells provides
      the background needed to target and disrupt specific IGF signaling pathways in an
      attempt to develop more effective therapies.

PMID- 14712219
TI  - Characterization of HBV integrants in 14 hepatocellular carcinomas: association
      of truncated X gene and hepatocellular carcinogenesis.
AB  - Although the integration of hepatitis B virus (HBV) into human DNA has been found
      to be associated with the development of hepatocellular carcinoma (HCC), the
      molecular mechanism remains unclear. In order to obtain additional insight into
      the correlation of HBV integration and HCC development, integrated HBV in 14
      primary HCC cases was isolated and characterized by sequencing analysis. Our
      findings in this study showed that: (1) none of the known cellular oncogene or
      tumor suppressor gene was affected by the HBV integration; (2) although the
      integration of HBV is random, the integration site was often within or close to
      human repetitive sequences; (3) integrated HBV may possess the capacity to
      transpose to another chromosome region through reintegration; (4) rearrangements
      of HBV sequence were observed in all the 14 integrants, involving (most
      frequently) X (12/14 integrants), P (8/14), S (7/14), and C (7/14) genes; and (5)
      3'-deleted X gene and consequent C-terminal truncated X protein caused by HBV
      integration was observed in 10 cases. These deletions cause the losses of p53
      dependent transcriptional repression binding site, transcription factor Sp1
      binding site, and growth-suppressive effect domain, leading to cell proliferation
      and transformation. This finding suggests that 3'-deleted X gene caused by the
      HBV integration may play an important role in the HCC development.

PMID- 14712220
TI  - TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric
      DNA.
AB  - The cancer-prone and premature aging disease Werner syndrome is due to loss of
      WRN gene function. Cells lacking WRN demonstrate genomic instability, including
      telomeric abnormalities and undergo premature senescence, suggesting defects in
      telomere metabolism. This notion is strongly supported by our finding of physical
      and functional interactions between WRN and TRF2, a telomeric repeat binding
      factor essential for proper telomeric structure. TRF2 binds to DNA substrates
      containing telomeric repeats and facilitates their degradation specifically by
      WRN exonuclease activity. WRN and TRF2 also interact directly in the absence of
      DNA. These results suggest that TRF2 recruits WRN for accurate processing of
      telomeric structures in vivo. Thus, our findings link problems in telomere
      maintenance to both carcinogenesis and specific features of aging.

PMID- 14712221
TI  - Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells.
AB  - The chemokine-CXCL12 and its receptor, CXCR4, have recently been shown to play an
      important role in regulating the directional migration of breast cancer cells to
      sites of metastasis. In the present study, we showed that CXCL12 enhanced the
      chemotaxis, chemoinvasion and adhesive properties of breast cancer cells;
      parameters that are critical for development of metastasis. We have also
      evaluated the signaling mechanisms that regulate CXCL12-induced and CXCR4
      mediated breast cancer cell motility and invasion. These studies revealed that
      CXCL12 induces the tyrosine phosphorylation of focal adhesion kinase (FAK) at
      residues 397 and 577, and of RAFTK/Pyk2 at residues 402 and 579/580. The
      cytoskeletal proteins paxillin and Crk, as well as tyrosine phosphatase SHP2 and
      adaptor protein Cbl, were also phosphorylated. CXCL12 induced the activation of
      PI 3-kinase, and increased its association with Cbl and SHP2. PI 3-kinase,
      RAFTK/Pyk2 and tyrosine phosphatase inhibitors significantly blocked CXCL12
      induced chemotaxis and chemoinvasion. The role of SHP2 and Cbl in CXCL12-induced
      chemotaxis and chemoinvasion in breast cancer cells was further defined by
      transiently overexpressing wild-type SHP2, wild-type Cbl, dominant-negative SHP2,
      Cbl mutants 70Z/3 and G306E or double transfectants of the Cbl and SHP2
      constructs. We found a novel role of Cbl in CXCL12-induced chemotaxis, which may
      be mediated through the activation and formation of a multimeric complex
      comprised of Cbl, SHP2 and PI 3-kinase. We also observed the activation of matrix
      metalloproteinases 2 and 9 upon CXCL12 stimulation. These studies provide new
      information regarding signaling pathways that may regulate CXCL12-induced
      metastasis in breast cancer cells.

PMID- 14712222
TI  - Stat3 enhances vimentin gene expression by binding to the antisilencer element
      and interacting with the repressor protein, ZBP-89.
AB  - Vimentin exhibits a complex pattern of developmental- and tissue-specific
      expression and is aberrantly expressed in most metastatic tumors. The human
      vimentin promoter contains multiple DNA elements, some of which enhance gene
      expression and one that inhibits. A silencer element (at -319) binds the
      repressor ZBP-89. Further upstream (at -757) is an element, which acts positively
      in the presence of the silencer element and, thus, is referred to as an
      antisilencer (ASE). Previously, we showed that Stat1alpha binds to this element
      upon induction by IFN-gamma. However, substantial binding and reporter gene
      activity was still present in nontreated cells. Here, we have found that Stat3
      binds to the ASE element in vitro. Transfection experiments in COS-1 cells with
      various vimentin promoter--reporter constructs show that gene activity is
      dependent upon the cotransfection and activation of Stat3. Moreover, activated
      Stat3 can overcome ZBP-89 repression. Coimmunoprecipitation studies demonstrate
      that Stat3 and ZBP-89 can interact and confocal microscopy detects these factors
      to be colocalized in the nucleus. Moreover, a correlation exists between the
      presence of activated Stat3 and vimentin expression in MDA-MB-231 cells, which is
      lacking in MCF7 cells where vimentin is not expressed. In the light of these
      results, we propose that the interaction of Stat3 and ZBP-89 may be crucial for
      overcoming the effects of the repressor ZBP-89, which suggests a novel mode for
      Stat3 gene activation.

PMID- 14712223
TI  - Microarray screening for target genes of the proto-oncogene PLAG1.
AB  - PLAG1 is a proto-oncogene whose ectopic expression can trigger the development of
      pleomorphic adenomas of the salivary glands and of lipoblastomas. As PLAG1 is a
      transcription factor, able to activate transcription through the binding to the
      consensus sequence GRGGC(N)(6-8)GGG, its ectopic expression presumably results in
      the deregulation of target genes, leading to uncontrolled cell proliferation. The
      identification of PLAG1 target genes is therefore a crucial step in understanding
      the molecular mechanisms involved in PLAG1-induced tumorigenesis. To this end, we
      analysed the changes in gene expression caused by the conditional induction of
      PLAG1 expression in fetal kidney 293 cell lines. Using oligonucleotide microarray
      analyses of about 12 000 genes, we consistently identified 47 genes induced and
      12 genes repressed by PLAG1. One of the largest classes identified as upregulated
      PLAG1 targets consists of growth factors such as the insulin-like growth factor
      II and the cytokine-like factor 1. The in silico search for PLAG1 consensus
      sequences in the promoter of the upregulated genes reveals that a large
      proportion of them harbor several copies of the PLAG1-binding motif, suggesting
      that they represent direct PLAG1 targets. Our approach was complemented by the
      comparison of the expression profiles of pleomorphic adenomas induced by PLAG1
      versus normal salivary glands. Concordance between these two sets of experiments
      pinpointed 12 genes that were significantly and consistently upregulated in
      pleomorphic adenomas and in PLAG1-expressing cells, identifying them as putative
      PLAG1 targets in these tumors.

PMID- 14712224
TI  - Activated Ras induces a proangiogenic phenotype in primary endothelial cells.
AB  - Angiogenic factors alter endothelial cell phenotype to promote the formation of
      new blood vessels, a process critical for a number of normal and pathological
      conditions. Ras is required for the induction of the angiogenic phenotype in
      response to vascular endothelial growth factor (VEGF). However, VEGF generates
      many signals, several of which are not dependent upon Ras activation. Our current
      study investigates the sufficiency of Ras activation for driving angiogenic
      responses. An activated Ras(V12) mutant induces prominent membrane ruffling,
      branching morphogenesis on three-dimensional collagen, DNA synthesis, and cell
      migration in primary endothelial cells. An upregulation of PI3K/AKT, Erk, and Jnk
      signaling pathways accompany these phenotypic changes. The inhibition of Erk
      blocked cell proliferation, but only partially attenuated migration. Blocking
      PI3K had no effect on DNA synthesis, but caused a modest reduction in cell
      migration. Lastly, Jnk played a significant role in both the proliferation and
      migration response. These effects of Ras(V12) are not the result of increased
      autocrine secretion of VEGF. These data suggest that the acquisition of
      activating Ras mutations can lead to a proangiogenic conversion in the phenotype
      of primary endothelial cells. Furthermore, these data raise the possibility that
      chronic Ras activation in endothelial cells may be sufficient to promote
      angiogenesis and the development of vascular anomalies.

PMID- 14712225
TI  - The tumor suppressor p16(INK4a) gene is a regulator of apoptosis induced by
      ultraviolet light and cisplatin.
AB  - p16(INK4a) (hereafter referred to as p16), a major cyclin-dependent kinase (CDK)
      inhibitor, is the product of a tumor-suppressor gene that has been found
      inactivated in different cancer types. In the present study, we sought to
      investigate the role of p16 in apoptosis induced by ultraviolet light (the most
      important etiological cause of skin cancer) and cisplatin (an anticancer DNA
      damaging agent). It is clearly shown that p16-compromised osteosarcoma U2OS cell
      line and p16-/- mouse embryo fibroblasts are sensitive to UV-induced apoptosis,
      as compared to their respective isogenic p16-expressing cells (EH1, EH2) and p16
      +/+, indicating that p16 protects cells from undergoing apoptosis in response to
      UV light. Importantly, this reduction in UV-mediated apoptosis was associated
      with downregulation of the proapoptotic Bax protein, with no effect on Bcl-2
      expression, suggesting that this antiapoptotic role of p16 is mediated via the
      intrinsic-mitochondrial pathway. On the other hand, p16 sensitized cells to
      cisplatin-mediated apoptosis through Bcl-2 decline. Interestingly, only
      proliferating but not G1-arrested EH1 cells underwent apoptosis in response to
      the anticancer drug. These novel findings provide further insight into the role
      of p16 in carcinogenesis, and has potential implications for future therapy
      strategies.

PMID- 14712226
TI  - The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation.
AB  - Neuroblastoma (NB) is a childhood cancer that arises in the adrenal gland and
      often shows differentiated neuronal and glial elements. The RET receptor signal
      pathway is functional in most NB, while loss of nerve growth factor (NGF)
      receptor (trkA) gene expression correlates with an aggressive phenotype. Thus, we
      hypothesized that the RET and TRKA signal pathways collaborate to instruct NB
      differentiation, reminiscent of normal neuronal maturation. Here, we demonstrate
      that activation of the RET receptor by glial cell line-derived neurotrophic
      factor (GDNF) increases expression of the RET receptor complex in a panel of
      malignant human NB cell lines, indicative of a positive feedback mechanism. GDNF
      also induces growth cessation concomitant with an arrest of cells in the
      G(0)/G(1) phase of the cell cycle. Furthermore, GDNF synergizes with ciliary
      neurotrophic factor (CNTF) to enhance TRKA receptor expression, thereby
      strengthening the NGF-mediated differentiation signal. Differentiated NB cells
      downregulate expression of the amplified N-myc gene, concurrent with the arrest
      of cell proliferation, while expressing neuron-specific markers (i.e., SCG10).
      Interestingly, maintenance of differentiated NB cells in culture is independent
      of the trophic activity of GDNF, but depends on TRKA signaling, thereby re
      enacting the differentiation of normal sympathoadrenal (SA) progenitor cells.

PMID- 14712227
TI  - Differential regulation of Jun N-terminal kinase and p38MAP kinase by Galpha12.
AB  - Based on the findings that the overexpression of the wild-type Galpha(12)
      (Galpha(12)WT) result in the oncogenic transformation of NIH3T3 cells in a serum
      dependent manner, a model system has been established in which the mitogenic and
      subsequent cell transformation pathways activated by Galpha(12) can be turned on
      or off by the addition or removal of serum. Using this model system, our previous
      studies have shown that the stimulation of Galpha(12)WT or the expression of an
      activated mutant of Galpha(12) (Galpha(12)QL) leads to increased cell
      proliferation and subsequent oncogenic transformation of NIH3T3 cells, as well as
      persistent activation of Jun N-terminal kinases (JNKs). In the present studies,
      we show that the stimulation of Galpha(12)WT or the expression of Galpha(12)QL
      results in a potent inhibition of p38MAPK, and that the mechanism by which
      Galpha(12) inhibits p38MAPK activity involves the dual specificity kinases
      upstream of p38MAPK. The results indicate that Galpha(12) attenuates the
      activation of MKK3 and MKK4, which are known to stimulate only p38MAPK or p38MAPK
      and JNK, respectively. The results also suggest that Galpha(12) activates JNKs
      specifically through the stimulation of the JNK-specific upstream kinase MKK7.
      These findings demonstrate for the first time that Galpha(12) differentially
      regulates JNK and p38MAPK by specifically activating MKK7, while inhibiting MKK3
      and MKK4 in NIH3T3 cells. Since the stimulation of p38MAPK is often associated
      with apoptotic responses, our findings suggest that Galpha(12) stimulates cell
      proliferation and neoplastic transformation of NIH3T3 cells by attenuating
      p38MAPK-associated apoptotic responses, while activating the mitogenic responses
      through the stimulation of ERK- and JNK-mediated signaling pathways.

PMID- 14712228
TI  - Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C
      terminal region regulates their in vivo Rho GEF activity and transforming
      potential.
AB  - PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho
      guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature
      consisting of the presence of an area of similarity to regulators of G protein
      signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which
      Galpha(12) and Galpha(13) can bind and regulate the activity of these RhoGEFs,
      thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ
      RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK,
      and associate with Plexin B, a semaphorin receptor, which controls axon guidance
      during development, through their PDZ domain, thereby stimulating Rho.
      Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a
      transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoGEF.
      Indeed, we observed that PDZ-RhoGEF and LARG can form homo- and hetero-oligomers,
      whereas p115RhoGEF can only homo-oligomerize, and that this intermolecular
      interaction was mediated by their unique C-terminal regions. Deletion of the C
      terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic
      activity towards Rho in vitro, but resulted in a drastic increase in the ability
      to stimulate a serum response element reporter and the accumulation of the GTP
      bound Rho in vivo. Furthermore, removal of the C-termini of each of the three RGL
      containing GEFs unleashed their full transforming potential. Together, these
      findings suggest the existence of a novel mechanism controlling the activity of
      PDZ-RhoGEF, LARG, and p115RhoGEF, which involves homo- and hetero-oligomerization
      through their inhibitory C-terminal region.

PMID- 14712229
TI  - G-protein-coupled receptor-mediated activation of rap GTPases: characterization
      of a novel Galphai regulated pathway.
AB  - Ras proteins mediate the proliferative effects of G-protein-coupled receptors
      (GPCRs), but the role of Rap proteins in GPCR signaling is unclear. We have
      developed a novel cellular proliferation assay for examining signal transduction
      to Rap utilizing Ras-rap chimeras that respond selectively to Rap-specific
      exchange factors, but which stimulate cellular proliferation through Ras
      effectors. Both the D1 dopamine receptor (Gs-coupled) and the 5HT1E serotonin
      receptor (Gi-coupled) mediated cellular proliferation in a Ras/rap chimera
      dependent manner. Responses to both receptors were PKA-independent. Both
      receptors activated Ras/rap and full-length Rap as measured by activation
      specific probes. Pertussis toxin blocked Ras/rap-dependent responses to 5HT1E but
      not D1. Ras/rap-dependent responses to both receptors were insensitive to beta
      gamma scavengers. Responses to 5HT1E, but not D1, were sensitive to inhibition by
      a dominant-negative C3G fragment, by the Src-like kinase inhibitors PP1 and PP2,
      and by a dominant-negative mutant of Src. Very similar data were obtained for two
      other Gi-coupled receptors, the D2 dopamine receptor and the alpha2C adrenergic
      receptor. A constitutively active mutant of Galphai2 also mediated Ras/rap
      dependent responses. These data indicate that GPCRs coupled to pertussis-toxin
      sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src
      dependent pathway.

PMID- 14712230
TI  - PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene
      silencing during cancer progression in an LNCaP model.
AB  - Transcriptional silencing of antitumor genes via CpG island methylation could be
      a mechanism mediating prostate cancer (PCa) progression from an androgen
      sensitive (AS) to an androgen-insensitive (AI) state. We have used the
      methylation-sensitive restriction fingerprinting (MSRF) technique to identify
      novel CpG-rich sequences that are differentially methylated between the genome of
      the AS PCa cell line LNCaP and that of an AI subline LNCaP(CS) generated by
      maintaining LNCaP in medium with charcoal-stripped (CS) serum for over 30
      passages. One such sequence identified was located on a 5' CpG island that was
      found to span part of the promoter, exon 1, and part of intron 1 of the
      peroxisomal membrane protein 24 kDa (PMP24) gene. Using semiquantitative RT-PCR
      and bisulfite genomic sequencing, we established an inverse relationship between
      mRNA expression and methylation of the 5' CpG island of PMP24. PMP24 mRNA was
      absent in LNCaP(CS) and the androgen receptor-negative PC-3 cell line; both
      exhibited dense methylation in the said CpG island. In contrast, PMP24 mRNA was
      expressed in LNCaP and normal prostatic epithelial cells (NPrECs) whose PMP24 5'
      CpG island remained unmethylated. Treatment of LNCaP(CS) and PC-3 with the
      demethylating agent 5-aza-2'-deoxycytidine (5-AZAdC) reactivated PMP24 mRNA
      expression. Transient transfection of PMP24 into LNCaP(CS) and PC-3 cells induced
      a significant reduction in cell growth and soft-agar colony formation potential,
      suggesting that PMP24 gene product has antitumor properties. These results
      demonstrate the utility of MSRF in the identification of novel, differentially
      methylated DNA sequences in the genome and suggest that hypermethylation-mediated
      silencing of PMP24 is an epigenetic event involved in PCa progression to androgen
      independence.

PMID- 14712231
TI  - Msh2 deficiency does not contribute to cisplatin resistance in mouse embryonic
      stem cells.
AB  - Several reports have suggested that a defect in the DNA mismatch repair (MMR)
      system not only causes resistance to methylating agents but also confers low
      level resistance to the chemotherapeutic drug cisplatin. Here we report that in a
      clonogenic assay, mouse embryonic stem (ES) cells deficient for the MMR protein
      MSH2 respond similarly as wild-type cells to cisplatin. Furthermore, restoring
      MSH2 expression in a cisplatin-resistant subclone selected from an Msh2(-/-) cell
      population did not sensitize cells to cisplatin. To ascertain that our
      observations were not the result of a mutation in the Msh2(-/-) cells that
      obscured the contribution of a defective MMR machinery to cisplatin resistance,
      we made use of the Cre-lox system to create a cell line in which the Msh2 gene
      can be conditionally inactivated. However, while de novo inactivation of Msh2
      rendered cells tolerant to the methylating drug N-methyl-N'-nitro-N
      nitrosoguanidine as expected, it did not alter the sensitivity to cisplatin. In
      addition, we were not able to derive cisplatin-resistant subclones from this
      freshly generated MMR-deficient cell line. Thus, in ES cells we did not find
      evidence for direct involvement of MMR deficiency in cisplatin resistance.

PMID- 14712232
TI  - Mapping and characterization of the minimal internal ribosome entry segment in
      the human c-myc mRNA 5' untranslated region.
AB  - The human c-myc proto-oncogene is transcribed from four alternative promoters
      generating transcripts with 5' untranslated regions of various lengths. These
      transcripts encode two proteins, c-Myc1 and c-Myc2, from two initiation codons,
      CUG and AUG, respectively. We and others have previously demonstrated that the
      region of c-myc transcripts between nucleotides (nt) -363 and -94 upstream from
      the CUG start codon contained an internal ribosome entry site leading to the cap
      independent translation of c-myc open reading frames (ORFs). Here, we mapped a 50
      nt sequence (-143 -94), which is sufficient to promote internal translation
      initiation of c-myc ORFs. Interestingly, this 50-nt element can be further
      dissected into two segments of 14 nt, each capable of activating internal
      translation initiation. We also demonstrate that this 50-nt element acts as the
      ribosome landing site from which the preinitiation ribosomal complex scans the
      mRNA until the CUG or AUG start codons.

PMID- 14712233
TI  - Transcriptional regulation of human osteopontin promoter by C/EBPalpha and AML-1
      in metastatic cancer cells.
AB  - Osteopontin (OPN) is a secreted glycoprotein produced by osteoclasts,
      macrophages, T cells, hematopoietic cells, and vascular smooth muscle cells. It
      contributes to macrophage homing and cellular immunity. It also mediates
      neovascularization, inhibits apoptosis, and plays important roles in
      extracellular matrix remodeling and angiogenesis. These properties are also
      characteristics of metastatic cancer cells. Consequently, the OPN gene was found
      to be upregulated among various metastatic cancer cells. This suggests that OPN
      is involved in tumor metastasis. How the OPN gene is upregulated in metastatic
      cancer cells remains to be illustrated. Thus, we investigated the transcriptional
      activation of the OPN promoter in the human metastatic cancer cell line A2058. We
      cloned the OPN promoter, and serial deletion analysis of the OPN promoter showed
      that the region between -170 and -127 may act as an enhancer to control the OPN
      gene in metastatic tumor cells. This region was found to contain overlapped AML-1
      and C/EBP binding site motifs. Gel-mobility-shift assays using the A2058 nuclear
      extract and AML-1a or C/EBPalpha (CCAAT/enhancer binding protein alpha)
      recombinant protein indicated that these two transcription factors can bind to
      the overlapped AML-1 /C/EBP binding site motifs on the OPN regulatory sequence
      from -147 to -127. Surprisingly, the gel-shift experiments did not show
      supershift complex formation between AML-1 and C/EBPalpha. Functional analysis
      showed that the C/EBPalpha was more potent than the complex of AML-1 and its
      cofactor CBFbeta to upregulate the OPN promoter. In addition, AML-1 and
      C/EBPalpha did not exhibit transactivation additively or synergistically. Our
      results suggest that AML-1 and C/EBPalpha play an important role in the
      upregulation of the OPN gene in metastatic tumor cells.

PMID- 14712234
TI  - Csk defines the ability of integrin-mediated cell adhesion and migration in human
      colon cancer cells: implication for a potential role in cancer metastasis.
AB  - Progression of human colon cancer is often associated with elevated expression
      and activity of the Src family tyrosine kinase (SFK). SFK is ordinarily in
      equilibrium between inactive and primed states by a balance of negative
      regulatory kinase Csk and its counteracting tyrosine phosphatase(s), both of
      which act on the regulatory C-terminal tyrosine of SFK. To evaluate the
      contribution of the regulatory system of SFK in cancer progression, we here
      modulated the equilibrium status of SFK by introducing wild-type or dominant
      negative Csk in human epithelial colon cancer cells, HCT15 and HT29.
      Overexpression of wild-type Csk induced decreased SFK activation, increased cell
      cell contacts mediated by E-cadherin, decreased the number of focal contacts and
      decreased cell adhesion/migration and in vitro invasiveness. Conversely,
      expression of a dominant-negative Csk resulted in elevated SFK activation,
      enhanced phosphorylation of FAK and paxilllin, enhanced cell scattering, an
      increased number of focal contacts, dramatic rearrangement of actin cytoskeleton
      and increased cell adhesion/migration and in vitro invasiveness. In these
      scattered cells, however, localization, expression and phosphorylation of either
      E-cadherin or beta-catenin were not significantly affected, suggesting that the E
      cadherin-mediated cell-cell contact is indirectly regulated by SFK. Furthermore,
      all these events occurred absolutely dependent on integrin-mediated cell
      adhesion. These findings demonstrate that Csk defines the ability of integrin-SFK
      mediated cell adhesion signaling that influences the metastatic potential of
      cancer cells.

PMID- 14712235
TI  - Absence of p21 partially rescues Mdm4 loss and uncovers an antiproliferative
      effect of Mdm4 on cell growth.
AB  - Mdm4 (MdmX) is a p53-binding protein that shares structural similarities with
      Mdm2 and has been proposed to be a negative regulator of p53 function. Like Mdm2,
      the absence of Mdm4 has recently been found to induce embryonic lethality in mice
      that is rescued by p53 deletion. Mdm4-null embryos are reduced in size and die at
      mid-gestation, and Mdm4-deficient embryos and embryonic fibroblasts displayed
      reduced rates of cell proliferation. The p53-induced, cyclin-dependent kinase
      inhibitor p21 is strongly upregulated in Mdm4-null embryos and cells. Here, we
      report that deletion of p21 delays the mid-gestation lethality observed in Mdm4
      null mice, suggesting that Mdm4 downregulates p53-mediated suppression of cell
      growth. Surprisingly, the absence of p21 also uncovers an antiproliferative
      effect of Mdm4 on cell growth in vitro and in Mdm4-heterozygous mice. These
      results indicate that p21 is a downstream modifier of Mdm4, and provides genetic
      evidence that Mdm4 can function to regulate cell growth both positively and
      negatively.

PMID- 14712236
TI  - Proteasome-dependent dispersal of PML nuclear bodies in response to alkylating
      DNA damage.
AB  - Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are present in variable
      number in most human cell types and have been linked to various cellular
      functions, including roles as depots for DNA repair proteins. Here, we show that
      treatment of human cells with DNA methylating agents leads to redistribution of
      PML from NBs to a diffuse nuclear localization. Biochemically, this correlates
      with a specific reduction of PML levels in the nuclear matrix fraction without
      affecting total PML levels. Similar results were obtained for the other major PML
      NB component, the Sp100 protein, indicating that DNA methylating agents lead to a
      general disassembly of PML NBs. Similar to the dispersal of PML NBs in response
      to some viral infections, PML redistribution after DNA damage was inhibited by
      the proteasome inhibitor MG132. We propose that the regulated dispersal of PML
      NBs may facilitate the enhanced release of DNA repair proteins from NB depots in
      order to respond adequately to extensive DNA damage.

PMID- 14712237
TI  - Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is
      widely expressed in normal tissues, including bone marrow, and it is not
      overexpressed in the t(1;3) cells.
AB  - Patients with myeloid malignancies and either the 3q21q26 syndrome or
      t(1;3)(p36;q21) have been reported to share similar clinicopathological features
      and a common molecular mechanism for leukemogenesis. Overexpression of MDS1/EVI1
      (3q26) or MEL1/PRDM16 (1p36), both members of the PR-domain family, has been
      directly implicated in the malignant transformation of this subset of neoplasias.
      The breakpoints in both entities are outside the genes, and the 3q21 region,
      where RPN1 is located, seems to act as an enhancer. MEL1 has been reported to be
      expressed in leukemia cells with t(1;3) and in the normal uterus and fetal
      kidney, but neither in bone marrow (BM) nor in other tissues, suggesting that
      this gene is specific to t(1;3)-positive MDS/AML. We report the molecular
      characterization of a t(1;3)(p36;q21) in a patient with MDS (RAEB-2). In contrast
      to previous studies, we demonstrate that MEL1, the PR-containing form, and MEL1S,
      the PR-lacking form, are widely expressed in normal tissues, including BM. The
      clinicopathological features and the breakpoint on 1p36 are different from cases
      previously described, and MEL1 is not overexpressed, suggesting a heterogeneity
      in myeloid neoplasias with t(1;3).

PMID- 14712238
TI  - Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel
      ANKTM1.
AB  - Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds.
      Topical application of mustard oil (allyl isothiocyanate) to the skin activates
      underlying sensory nerve endings, thereby producing pain, inflammation and robust
      hypersensitivity to thermal and mechanical stimuli. Despite their widespread use
      in both the kitchen and the laboratory, the molecular mechanism through which
      isothiocyanates mediate their effects remains unknown. Here we show that mustard
      oil depolarizes a subpopulation of primary sensory neurons that are also
      activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)
      tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl
      isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a
      member of the TRP ion channel family recently implicated in the detection of
      noxious cold. These findings identify a cellular and molecular target for the
      pungent action of mustard oils and support an emerging role for TRP channels as
      ionotropic cannabinoid receptors.

PMID- 14712239
TI  - The red planet's big picture.

PMID- 14712241
TI  - Rover barks before Beagle as Mars success lifts NASA's spirits.

PMID- 14712240
TI  - China and SARS: could do better.

PMID- 14712243
TI  - Yucca review-board head quits in face of impartiality charges.

PMID- 14712242
TI  - Swift response greets return of SARS in China.

PMID- 14712244
TI  - Safety concerns prompt US ban on dietary supplement.

PMID- 14712245
TI  - Geneticists chip away at unruly data.

PMID- 14712246
TI  - Canadian prime minister makes science a priority.

PMID- 14712249
TI  - Automatic archaeology.

PMID- 14712248
TI  - Hungarian science: dreaming on the Danube.

PMID- 14712250
TI  - Fertilizer: no-till farming could reduce run-off.

PMID- 14712251
TI  - Fertilizer: complex issue calls for informed debate.

PMID- 14712252
TI  - Cooperation needed to increase fertilizer efficiency.

PMID- 14712256
TI  - A glass bead game.

PMID- 14712257
TI  - Stem cells: how to make eggs and sperm.

PMID- 14712258
TI  - Ecology: clouded futures.

PMID- 14712260
TI  - Astronomy: to catch a stellar thief.

PMID- 14712261
TI  - Cancer: guarding the guardian?

PMID- 14712262
TI  - Developmental biology: asymmetric fixation.

PMID- 14712263
TI  - Plant development: the flowers that bloom in the spring.

PMID- 14712265
TI  - Explosive craters and soil liquefaction.

PMID- 14712266
TI  - Acoustics: tuning of vocal tract resonance by sopranos.

PMID- 14712267
TI  - Dating the rise of atmospheric oxygen.
AB  - Several lines of geological and geochemical evidence indicate that the level of
      atmospheric oxygen was extremely low before 2.45 billion years (Gyr) ago, and
      that it had reached considerable levels by 2.22 Gyr ago. Here we present evidence
      that the rise of atmospheric oxygen had occurred by 2.32 Gyr ago. We found that
      syngenetic pyrite is present in organic-rich shales of the 2.32-Gyr-old
      Rooihoogte and Timeball Hill formations, South Africa. The range of the isotopic
      composition of sulphur in this pyrite is large and shows no evidence of mass
      independent fractionation, indicating that atmospheric oxygen was present at
      significant levels (that is, greater than 10(-5) times that of the present
      atmospheric level) during the deposition of these units. The presence of rounded
      pebbles of sideritic iron formation at the base of the Rooihoogte Formation and
      an extensive and thick ironstone layer consisting of haematitic pisolites and
      oolites in the upper Timeball Hill Formation indicate that atmospheric oxygen
      rose significantly, perhaps for the first time, during the deposition of the
      Rooihoogte and Timeball Hill formations. These units were deposited between what
      are probably the second and third of the three Palaeoproterozoic glacial events.

PMID- 14712269
TI  - The massive binary companion star to the progenitor of supernova 1993J.
AB  - The massive star that underwent a collapse of its core to produce supernova
      (SN)1993J was subsequently identified as a non-variable red supergiant star in
      images of the galaxy M81 taken before explosion. It showed an excess in
      ultraviolet and B-band colours, suggesting either the presence of a hot, massive
      companion star or that it was embedded in an unresolved young stellar
      association. The spectra of SN1993J underwent a remarkable transformation from
      the signature of a hydrogen-rich type II supernova to one of a helium-rich
      (hydrogen-deficient) type Ib. The spectral and photometric peculiarities were
      best explained by models in which the 13-20 solar mass supergiant had lost almost
      its entire hydrogen envelope to a close binary companion, producing a 'type IIb'
      supernova, but the hypothetical massive companion stars for this class of
      supernovae have so far eluded discovery. Here we report photometric and
      spectroscopic observations of SN1993J ten years after the explosion. At the
      position of the fading supernova we detect the unambiguous signature of a massive
      star: the binary companion to the progenitor.

PMID- 14712268
TI  - Notch activity acts as a sensor for extracellular calcium during vertebrate left
      right determination.
AB  - During vertebrate embryo development, the breaking of the initial bilateral
      symmetry is translated into asymmetric gene expression around the node and/or in
      the lateral plate mesoderm. The earliest conserved feature of this asymmetric
      gene expression cascade is the left-sided expression of Nodal, which depends on
      the activity of the Notch signalling pathway. Here we present a mathematical
      model describing the dynamics of the Notch signalling pathway during chick embryo
      gastrulation, which reveals a complex and highly robust genetic network that
      locally activates Notch on the left side of Hensen's node. We identify the source
      of the asymmetric activation of Notch as a transient accumulation of
      extracellular calcium, which in turn depends on left-right differences in H+/K+
      ATPase activity. Our results uncover a mechanism by which the Notch signalling
      pathway translates asymmetry in epigenetic factors into asymmetric gene
      expression around the node.

PMID- 14712270
TI  - An intense stratospheric jet on Jupiter.
AB  - The Earth's equatorial stratosphere shows oscillations in which the east-west
      winds reverse direction and the temperatures change cyclically with a period of
      about two years. This phenomenon, called the quasi-biennial oscillation, also
      affects the dynamics of the mid- and high-latitude stratosphere and weather in
      the lower atmosphere. Ground-based observations have suggested that similar
      temperature oscillations (with a 4-5-yr cycle) occur on Jupiter, but these data
      suffer from poor vertical resolution and Jupiter's stratospheric wind velocities
      have not yet been determined. Here we report maps of temperatures and winds with
      high spatial resolution, obtained from spacecraft measurements of infrared
      spectra of Jupiter's stratosphere. We find an intense, high-altitude equatorial
      jet with a speed of approximately 140 m s(-1), whose spatial structure resembles
      that of a quasi-quadrennial oscillation. Wave activity in the stratosphere also
      appears analogous to that occurring on Earth. A strong interaction between
      Jupiter and its plasma environment produces hot spots in its upper atmosphere and
      stratosphere near its poles, and the temperature maps define the penetration of
      the hot spots into the stratosphere.

PMID- 14712271
TI  - Hybridization of electronic states in quantum dots through photon emission.
AB  - The self-assembly of semiconductor quantum dots has opened up new opportunities
      in photonics. Quantum dots are usually described as 'artificial atoms', because
      electron and hole confinement gives rise to discrete energy levels. This picture
      can be justified from the shell structure observed as a quantum dot is filled
      either with excitons (bound electron-hole pairs) or with electrons. The discrete
      energy levels have been most spectacularly exploited in single photon sources
      that use a single quantum dot as emitter. At low temperatures, the artificial
      atom picture is strengthened by the long coherence times of excitons in quantum
      dots, motivating the application of quantum dots in quantum optics and quantum
      information processing. In this context, excitons in quantum dots have already
      been manipulated coherently. We show here that quantum dots can also possess
      electronic states that go far beyond the artificial atom model. These states are
      a coherent hybridization of localized quantum dot states and extended continuum
      states: they have no analogue in atomic physics. The states are generated by the
      emission of a photon from a quantum dot. We show how a new version of the
      Anderson model that describes interactions between localized and extended states
      can account for the observed hybridization.

PMID- 14712272
TI  - Detection of molecular interactions at membrane surfaces through colloid phase
      transitions.
AB  - The molecular architecture of-and biochemical processes within--cell membranes
      play important roles in all living organisms, with many drugs and infectious
      disease agents targeting membranes. Experimental studies of biochemical reactions
      on membrane surfaces are challenging, as they require a membrane environment that
      is fluid (like cell membranes) but nevertheless allows for the efficient
      detection and characterization of molecular interactions. One approach uses lipid
      membranes supported on solid substrates such as silica or polymers: although the
      membrane is trapped near the solid interface, it retains natural fluidity and
      biological functionality and can be implanted with membrane proteins for
      functional studies. But the detection of molecular interactions involving
      membrane-bound species generally requires elaborate techniques, such as surface
      plasmon resonance or total internal reflection fluorescence microscopy. Here we
      demonstrate that colloidal phase transitions of membrane-coated silica beads
      provide a simple and label-free method for monitoring molecular interactions on
      lipid membrane surfaces. By adjusting the lipid membrane composition and hence
      the pair interaction potential between the membrane-supporting silica beads, we
      poise our system near a phase transition so that small perturbations on the
      membrane surface induce dramatic changes in the macroscopic organization of the
      colloid. We expect that this approach, used here to probe with high sensitivity
      protein binding events at membrane surfaces, can be applied to study a broad
      range of cell membrane processes.

PMID- 14712273
TI  - Critically pressured free-gas reservoirs below gas-hydrate provinces.
AB  - Palaeoceanographic data have been used to suggest that methane hydrates play a
      significant role in global climate change. The mechanism by which methane is
      released during periods of global warming is, however, poorly understood. In
      particular, the size and role of the free-gas zone below gas-hydrate provinces
      remain relatively unconstrained, largely because the base of the free-gas zone is
      not a phase boundary and has thus defied systematic description. Here we evaluate
      the possibility that the maximum thickness of an interconnected free-gas zone is
      mechanically regulated by valving caused by fault slip in overlying sediments.
      Our results suggest that a critical gas column exists below most hydrate
      provinces in basin settings, implying that these provinces are poised for
      mechanical failure and are therefore highly sensitive to changes in ambient
      conditions. We estimate that the global free-gas reservoir may contain from one
      sixth to two-thirds of the total methane trapped in hydrate. If gas accumulations
      are critically thick along passive continental slopes, we calculate that a 5
      degrees C temperature increase at the sea floor could result in a release of
      approximately 2,000 Gt of methane from the free-gas zone, offering a mechanism
      for rapid methane release during global warming events.

PMID- 14712274
TI  - Extinction risk from climate change.
AB  - Climate change over the past approximately 30 years has produced numerous shifts
      in the distributions and abundances of species and has been implicated in one
      species-level extinction. Using projections of species' distributions for future
      climate scenarios, we assess extinction risks for sample regions that cover some
      20% of the Earth's terrestrial surface. Exploring three approaches in which the
      estimated probability of extinction shows a power-law relationship with
      geographical range size, we predict, on the basis of mid-range climate-warming
      scenarios for 2050, that 15-37% of species in our sample of regions and taxa will
      be 'committed to extinction'. When the average of the three methods and two
      dispersal scenarios is taken, minimal climate-warming scenarios produce lower
      projections of species committed to extinction ( approximately 18%) than mid
      range ( approximately 24%) and maximum-change ( approximately 35%) scenarios.
      These estimates show the importance of rapid implementation of technologies to
      decrease greenhouse gas emissions and strategies for carbon sequestration.

PMID- 14712275
TI  - T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases.
AB  - Primary T-cell responses in lymph nodes (LNs) require contact-dependent
      information exchange between T cells and dendritic cells (DCs). Because
      lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool
      is composed of non-synchronized cells with different dwell times that display
      heterogeneous behaviour in mouse LNs in vitro. Here we employ two-photon
      microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell
      time in LNs was synchronized. During the first 8 h after entering from the blood,
      T cells underwent multiple short encounters with DCs, progressively decreased
      their motility, and upregulated activation markers. During the subsequent 12 h T
      cells formed long-lasting stable conjugates with DCs and began to secrete
      interleukin-2 and interferon-gamma. On the second day, coinciding with the onset
      of proliferation, T cells resumed their rapid migration and short DC contacts.
      Thus, T-cell priming by DCs occurs in three successive stages: transient serial
      encounters during the first activation phase are followed by a second phase of
      stable contacts culminating in cytokine production, which makes a transition into
      a third phase of high motility and rapid proliferation.

PMID- 14712276
TI  - Vernalization in Arabidopsis thaliana is mediated by the PHD finger protein VIN3.
AB  - In biennials and winter annuals, flowering is typically blocked in the first
      growing season. Exposure to the prolonged cold of winter, through a process
      called vernalization, is required to alleviate this block and permit flowering in
      the second growing season. In winter-annual types of Arabidopsis thaliana, a
      flowering repressor, FLOWERING LOCUS C (FLC), is expressed at levels that inhibit
      flowering in the first growing season. Vernalization promotes flowering by
      causing a repression of FLC that is mitotically stable after return to warm
      growing conditions. Here we identify a gene with a function in the measurement of
      the duration of cold exposure and in the establishment of the vernalized state.
      We show that this silencing involves changes in the modification of histones in
      FLC chromatin.

PMID- 14712280
TI  - Healthy limits.

PMID- 14712277
TI  - Vernalization requires epigenetic silencing of FLC by histone methylation.
AB  - To ensure flowering in favourable conditions, many plants flower only after an
      extended period of cold, namely winter. In Arabidopsis, the acceleration of
      flowering by prolonged cold, a process called vernalization, involves
      downregulation of the protein FLC, which would otherwise prevent flowering. This
      lowered FLC expression is maintained through subsequent development by the
      activity of VERNALIZATION (VRN) genes. VRN1 encodes a DNA-binding protein whereas
      VRN2 encodes a homologue of one of the Polycomb group proteins, which maintain
      the silencing of genes during animal development. Here we show that vernalization
      causes changes in histone methylation in discrete domains within the FLC locus,
      increasing dimethylation of lysines 9 and 27 on histone H3. Such modifications
      identify silenced chromatin states in Drosophila and human cells. Dimethylation
      of H3 K27 was lost only in vrn2 mutants, but dimethylation of H3 K9 was absent
      from both vrn1 and vrn2, consistent with VRN1 functioning downstream of VRN2. The
      epigenetic memory of winter is thus mediated by a 'histone code' that specifies a
      silent chromatin state conserved between animals and plants.

PMID- 14712281
TI  - Graduate journal: from biochemist to engineer.

PMID- 14712282
TI  - Nuts and bolts: career journals.

PMID- 14712284
TI  - Impaired stem cell function of CD34+ cells selected by two different
      immunomagnetic beads systems.
AB  - We have been investigating the hematopoietic stem cell (HSC) activity of
      peripheral blood-derived CD34(+) cells selected by two different laboratory
      immunomagnetic beads systems (MiniMACS and Isolex 50). In this study, the quality
      of purified CD34(+) cells was directly compared using clonal cell culture, a
      cobblestone area-forming cell (CAFC) assay, and an in vivo severe combined
      immunodeficiency (SCID)-repopulating cell (SRC) assay. It was found that CD34(+)
      cells selected by these two immunomagnetic methods showed a reduced yield of
      colony-forming cells and CAFCs compared with cells enriched by the StemSep device
      (a negative selection method). However, these CD34(+) cells still showed
      significant SRC activity, including multilineage lymphomyeloid reconstitution.
      The percentage of human CD45(+) cells in murine bone marrow after transplanting 5
      x 10(5) CD34(+) cells selected by the Isolex 50 was significantly lower than
      after transplanting cells selected by the MiniMACS or the StemSep. Our findings
      clearly demonstrated that CD34(+) cells selected by the MiniMACS system had
      superior HSC functions, including SRC activity, compared with cells separated by
      the Isolex 50 system. More detailed functional analysis of immunomagnetically
      separated CD34(+) cells may provide useful knowledge for basic research on HSCs
      as well as for clinical HSC transplantation.

PMID- 14712285
TI  - A prospective, randomised, phase II study of horse antithymocyte globulin vs
      rabbit antithymocyte globulin as immune-modulating therapy in patients with low
      risk myelodysplastic syndromes.
AB  - Immunosuppression has recently been proposed for low-risk myelodysplastic
      syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary
      secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory
      anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia)
      with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte
      globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75).
      After 1 to 34+ months of follow-up (mean: 15+), four patients experienced
      complete haematological responses (CR), six good responses (GR) and two minor
      responses. All CRs and GRs occurred in patients with RA, in whom both horse and
      rabbit ATG yielded five responses out of 12 (42%). Time to response varied
      between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+)
      months; five patients are in continuing response. In all, 23 patients suffered
      side effects > degrees II WHO (the degree of toxicity encountered according to
      the internationally accepted WHO toxicity grading); one patient died 2 weeks
      after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with
      response were duration of disease and RA subgroup. In our experience, immune
      modulating therapy with either horse or rabbit ATG is feasible in patients with
      RA and short duration of disease.

PMID- 14712286
TI  - Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal
      diffuse large B-cell lymphomas.
AB  - Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable,
      despite the identification of clinical prognostic parameters. Here, we
      investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers
      of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of
      CD3-positive lymphocytes with granzyme B (GrB) expression, have similar
      prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell
      lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules
      or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune
      escape from CTL-mediated cell death. Independent of the International Prognostic
      Index (IPI), the presence of >/=15% activated CTLs was strongly associated with
      failure to reach complete remission, with a poor progression-free and overall
      survival time. Downregulation of MHC-I light- and/or heavy-chain expression was
      found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9
      expression was detected. We conclude that a high percentage of activated CTLs is
      a strong, IPI independent, indicator for an unfavorable clinical outcome in
      patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9
      and loss of MHC-I expression was found, providing a possible immune-escape
      mechanism in these cases, no correlation with clinical outcome was found.

PMID- 14712287
TI  - Chronic lymphocytic leukemia with 6q- shows distinct hematological features and
      intermediate prognosis.
AB  - Cytogenetic and fluorescence in situ hybridization studies were successfully
      performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with
      6q21 deletion were identified and characterized in comparison with 92 patients
      with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk'
      (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p
      ). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a
      finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6
      cases. IGVH mutational status revealed >98% homology to the germline sequence in
      4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a
      higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology,
      CD38+ and short time from diagnosis to first treatment and short survival. A
      higher median WBC count was found in the 6q- group vs the intermediate-risk
      group; survival was shorter in the unfavourable group. To ascertain if the 6q-
      anomaly was an independent factor predicting for an inferior outcome among those
      patients with 'favourable' cytogenetics, we performed an analysis of prognostic
      factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q-
      chromosome maintained its prognostic significance at multivariate analysis
      (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is
      characterized by a high incidence of atypical morphology, classical
      immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic
      hypermutation. Clinicobiological features and outcome show that this cytogenetic
      subset of CLL should be allocated in an intermediate-risk category.

PMID- 14712288
TI  - Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of
      B-cell lymphoma.
AB  - NZB mice develop an age-related malignant expansion of a subset of B cells, B-1
      cells, with autocrine production of IL-10. IL-10, a pleiotropic cytokine with
      anti-inflammatory properties, is a potent growth and survival factor for
      malignant B cells. To further examine the in vivo requirement for IL-10 in the
      development and expansion of malignant B-1 clones in NZB mice, we developed a
      strain of homozygous IL-10 knockout (KO) mice on an NZB background. The NZB IL-10
      KO mice develop peritoneal B-1 cells with approximately the same frequency as
      heterozygous and wild-type littermates. In contrast, the development of malignant
      B-1 cells in the peripheral blood and spleen, observed in wild-type NZB, rarely
      occurred in the NZB IL-10 KO. Phenotypic analysis of surface marker expression in
      splenic B cells indicated that, in contrast to the NZB with malignant B-1 splenic
      lymphoma, the surface marker expression of NZB IL-10 KO splenic B cells indicated
      that the majority of the B cells were typical B-2 cells. In the absence of IL-10,
      spontaneously activated B cells and antiapoptotic gene expression were reduced
      and lymphoma incidence was decreased. These results indicate that IL-10 is a
      critical factor for the progression of this B-cell malignant disease.

PMID- 14712289
TI  - N-(4-hydroxyphenyl)retinamide induces growth arrest and apoptosis in HTLV-I
      transformed cells.
AB  - N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth
      and induces apoptosis in many human cell lines. We explored the effects of HPR on
      human T-cell lymphotropic virus type I (HTLV-I)-positive and HTLV-I-negative
      malignant T-cell lines, most of which are resistant to all-trans retinoic acid.
      Clinically achievable concentrations of HPR caused a dramatic inhibition of cell
      proliferation, G(0)/G(1) arrest, and massive apoptosis in all tested malignant T
      cells, while no effect was observed on resting or activated normal lymphocytes.
      Interestingly, HTLV-I-negative cell lines were significantly more sensitive to
      HPR compared to HTLV-I-positive and Tax-transfected cells. In HTLV-I-negative
      cells only, HPR-induced apoptosis was associated with ceramide accumulation,
      sharp decrease in mitochondrial membrane potential, and activation of caspases 8,
      9 and 3, and could be partially reverted by the caspase inhibitor z-VAD
      suggesting that Tax protects infected cells from ceramide accumulation and
      caspase-mediated apoptosis. In HTLV-I-positive cells, HPR treatment rapidly
      induced proteasomal-mediated degradation of p21, downregulated cyclin D(1), and
      upregulated bax protein levels. These findings support a potential therapeutic
      role for HPR in both HTLV-I-associated adult T-cell leukemia/lymphoma (ATL) and
      HTLV-I-negative peripheral T-cell lymphomas.

PMID- 14712290
TI  - Imatinib sensitizes CLL lymphocytes to chlorambucil.
AB  - The effect of imatinib on chlorambucil (CLB) cytotoxicity in chronic lymphocytic
      leukemia (CLL) lymphocytes was examined in vitro. Imatinib sensitizes the WSU and
      I83 human CLL cell lines, 10- and two-fold, respectively, to CLB. Furthermore, in
      primary cultures of malignant B-lymphocytes obtained from 12 patients with CLL
      (seven patients were untreated and five treated with CLB), imatinib
      synergistically sensitized these lymphocytes from two- to 20-fold to CLB. This
      synergistic effect was observed at concentrations of imatinib (</=10 microM),
      which are achievable in patients with minimal toxicity. Moreover, the combination
      of both drugs results in increased apoptosis in CLL cell lines. These results
      suggest that imatinib should be useful in improving the therapeutic index of CLB
      in CLL. The mechanism of action appears to involve imatinib inhibition of c-abl
      kinase activity with an associated decrease in CLB-induced Rad51 phosphorylation
      and CLB-induced Rad51 nuclear foci, suggesting that imatinib decreases Rad51
      related DNA repair of CLB-induced DNA lesions. Altogether, our results suggest
      that imatinib is a promising adjuvant therapy to CLB treatment of CLL.

PMID- 14712291
TI  - In vitro drug-resistance profile in infant acute lymphoblastic leukemia in
      relation to age, MLL rearrangements and immunophenotype.
AB  - Acute lymphoblastic leukemia (ALL) in infants under 1 year is strongly associated
      with translocations involving 11q23 (MLL gene), CD10-negative B-lineage (proB)
      immunophenotype, and poor outcome. The present study analyses the relationship
      between age, MLL rearrangements, proB-lineage, and in vitro drug resistance
      determined using the MTT assay. Compared to 425 children aged over 1 year with
      common/preB (c/preB) ALL, the 44 infants were highly resistant to steroids (for
      prednisolone (PRED) more than 580-fold, P=0.001) and L-asparaginase (L-ASP) (12
      fold, P=0.001), but more sensitive to cytarabine (AraC) (1.9-fold, P=0.001) and 2
      chlorodeoxyadenosine (2-CdA) (1.7-fold, P<0.001). No differences were found for
      vincristine, anthracyclines, thiopurines, epipodophyllotoxines, or 4-hydroperoxy
      (HOO)-ifosfamide. ProB ALL of all ages had a profile similar to infant ALL when
      compared with the group of c/preB ALL: relatively more resistant to L-ASP and
      PRED (and in addition thiopurines), and more sensitive to AraC and 2-CdA. Age was
      not related to cellular drug resistance within the proB ALL group (<1 year, n=32,
      vs >/=1 year, n=19), nor within the MLL-rearranged ALL (<1 year, n=34, vs >/=1
      year, n=8). The translocation t(4;11)(q21;q23)-positive ALL cases were more
      resistant to PRED (>7.4-fold, P=0.033) and 4-HOO-ifosfamide (4.4-fold, P=0.006)
      than those with other 11q23 abnormalities. The expression of P-glycoprotein,
      multidrug-resistance protein, and lung-resistance protein (LRP) was not higher in
      infants compared to older c/preB ALL patients, but LRP was higher in proB ALL and
      MLL-rearranged ALL of all ages. In conclusion, infants with ALL appear to have a
      distinct in vitro resistance profile with the proB immunophenotype being of
      importance. The role of MLL cannot be excluded, with the t(4;11) being of special
      significance, while age appears to play a smaller role.

PMID- 14712292
TI  - Inactivation of the ARF-MDM-2-p53 pathway in sporadic Burkitt's lymphoma in
      children.
AB  - Burkitt's lymphomas (BLs) are characterized by an activated MYC gene that
      provides a constitutive proliferative signal. However, activated myc can initiate
      ARF-dependent activation of p53 and apoptosis as well. Data derived from cell
      culture and animal models suggest that the inactivation of the ARF-MDM-2-p53
      apoptotic signaling pathway may be a necessary secondary event for the
      development of BL. This has not been tested in freshly excised BL tissue. We
      investigated the ARF-MDM-2-p53 pathway in tumor specimen from 24 children with
      sporadic BL/B-ALL. Direct sequencing revealed a point mutation in the p53 gene in
      four BL. Overexpression of MDM-2 was evident in 10 of the BL samples analyzed by
      real-time quantitative PCR. Deletion of the CDKN2A locus that encodes ARF or
      reduced expression of ARF could not be detected in any BL by fluorescence in situ
      hybridization analysis or real-time quantitative PCR, respectively. Our results
      indicate that the ARF-MDM-2-p53 apoptotic pathway is disrupted in about 55% of
      the cases of childhood sporadic BL. We suggest that in addition to the
      inactivation of the ARF-MDM-2-p53 protective checkpoint function other
      antiapoptotic mutations may occur in a substantial part of children with sporadic
      BL.

PMID- 14712293
TI  - Establishment and phenotypic characterization of human U937 cells with inducible
      P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a).
AB  - Chronic myeloid leukemia (CML) is characterized by the expression of the P210
      BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated
      hematological disease are, however, not fully understood. Here, we describe the
      establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL
      can be conditionally expressed using tetracycline. The induction of BCR/ABL in
      the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and
      STAT5 molecules, consistent with the findings in other model systems. Phenotypic
      characterization of the clones revealed that BCR/ABL induces a slight decrease in
      the proliferation and viability, without a marked effect on cell cycle
      distribution, the rate of apoptosis or on cellular differentiation, as judged by
      several cell surface markers and capacity to reduce nitro blue tetrazolium.
      Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic
      related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein
      belonging to the CEAs and involved in signal transduction and cellular adhesion.
      The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL
      expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established
      cell lines may prove useful in further modeling and dissection of BCR/ABL-induced
      leukemogenesis.

PMID- 14712294
TI  - Chromosomal abnormalities clustering in multiple myeloma reveals cytogenetic
      subgroups with nonrandom acquisition of chromosomal changes.

PMID- 14712295
TI  - Gene therapy progress and prospects: noninvasive imaging of gene therapy in
      living subjects.
AB  - Recent progress in the development of noninvasive imaging technologies should
      allow molecular imaging to play a major role in the field of gene therapy. These
      tools have recently been validated in gene therapy models for continuous
      quantitative monitoring of the location(s), magnitude, and time variation of gene
      delivery and/or expression. This article reviews the use of radionuclide,
      magnetic resonance, and optical imaging technologies, as they have been used in
      imaging gene delivery and gene expression for gene therapy applications. The
      studies published to date lend support that noninvasive imaging tools will help
      to accelerate preclinical model validation, as well as allow for clinical
      monitoring of human gene therapy.

PMID- 14712296
TI  - Inhibition of neointimal hyperplasia after balloon injury by cis-element 'decoy'
      of early growth response gene-1 in hypercholesterolemic rabbits.
AB  - Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly
      activated after vascular injury and thus might contribute to vascular
      proliferation and inflammation. We hypothesized that Egr-1 might therefore be a
      therapeutic target against restenosis. Hypercholesterolemic rabbits were
      intraluminally administered synthetic DNA as a 'decoy' against Egr-1 immediately
      after carotid artery balloon injury. Efficient transfection was confirmed by the
      delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed
      increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy
      transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and
      proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy
      transfection reduced gene expression and protein production of Egr-1-dependent
      genes such as platelet-derived growth factor-B, transforming growth factor-beta1,
      and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role
      in the pathogenesis of neointimal hyperplasia after balloon injury in
      hypercholesterolemic rabbits. This decoy strategy is a potential practical form
      of therapy for human restenosis.

PMID- 14712297
TI  - Gene delivery to cartilage defects using coagulated bone marrow aspirate.
AB  - The long-term goal of the present study is to develop a clinically applicable
      approach to enhance natural repair mechanisms within cartilage lesions by
      targeting bone marrow-derived cells for genetic modification. To determine if
      bone marrow-derived cells infiltrating osteochondral defects could be transduced
      in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with
      adenoviral vectors containing various marker genes into lesions surgically
      generated in rabbit femoral condyles. Analysis of the recovered implants showed
      transgenic expression up to 21 days; however, a considerable portion was found in
      the synovial lining, indicating leakage of the vector and/or transduced cells
      from the matrix. As an alternative medium for gene delivery, we investigated the
      feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral
      suspension with the fluid phase of freshly aspirated bone marrow resulted in
      uniform dispersion of the vector throughout, and levels of transgenic expression
      in direct proportion to the density of nucleated cells in the ensuing clot.
      Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex
      vivo with recombinant adenovirus, were readily incorporated into the coagulate
      when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow
      clots were found to maintain their structural integrity following extensive
      culture and maintained transgenic expression in this manner for several weeks.
      When used in place of the CG matrix as a gene delivery vehicle in vivo,
      genetically modified bone marrow clots were able to generate similarly high
      levels of transgenic expression in osteochondral defects with better containment
      of the vector within the defect. Our results suggest that coagulates formed from
      aspirated bone marrow may be useful as a means of gene delivery to cartilage and
      perhaps other musculoskeletal tissues. Cells within the fluid can be readily
      modified with an adenoviral vector, and the matrix formed from the clot is
      completely natural, native to the host and is the fundamental platform on which
      healing and repair of mesenchymal tissues is based.

PMID- 14712298
TI  - 5-Fluorocytosine increases the toxicity of Wnt-targeting replicating adenoviruses
      that express cytosine deaminase as a late gene.
AB  - Clinical studies with oncolytic adenoviruses have shown that existing viruses are
      safe but lack efficacy. To selectively increase the toxicity of oncolytic
      adenoviruses targeting colon tumours, we have inserted the yeast cytosine
      deaminase gene (yCD) after the fibre gene in the major late transcript. yCD was
      expressed using either an internal ribosome entry site (IRES) or by alternative
      splicing of a new exon analogous to the Ad41 long fibre exon. The IRES-CD virus
      gave higher yCD expression on Western blots. Both approaches result in yCD
      expression restricted to the period after viral DNA replication. Viral burst size
      was reduced by less than approximately 10-fold by 5-fluorocytosine (5-FC),
      showing that expression of yCD as a late gene is compatible with virus
      replication. Cytopathic effect assays in colon cancer cell lines showed that both
      yCD viruses have approximately 10-fold increased toxicity in the presence of the
      prodrug 5-FC, which is converted to 5-fluorouracil (5-FU) by yCD. Toxicity was
      higher following addition of 5-FC immediately after infection. The largest gain
      in toxicity was seen in HT29 colon cancer cells, which are the least permissive
      colon cancer cells for the parental virus, indicating that the new 5-FC/yCD
      viruses may have broader applications for colon cancer therapy than their
      predecessors.

PMID- 14712299
TI  - Transgene expression is increased by photochemically mediated transduction of
      polycation-complexed adenoviruses.
AB  - Poor efficiency of adenoviral gene transfer to target cells is a major limitation
      to adenoviral gene therapy. Inefficient gene transfer occurs in the absence of
      coxsackie- and adenovirus receptor (CAR) on the cell surface, and can be overcome
      by enhancing viral entry with cationic molecules. Recombinant adenovirus (Ad)
      noncovalently complexed with polycations imply a lack of transduction
      specificity. Therefore, we have investigated the potential of a novel light
      specific treatment, named photochemical internalization (PCI), to enhance gene
      delivery of adenovirus serotype 5 (Ad5) complexed with the cationic agents poly-L
      lysine (PLL) and SuperFect trade mark. Cell lines differing in their
      receptiveness to Ad5 were infected with amounts of virus transducing about 2% of
      the cells by conventional Ad infection. The combination of polycations and
      photochemical treatment enabled a substantial increase in reporter gene
      expression, resulting in up to 75% positive cells. The effect was most prominent
      in cell lines expressing moderate to low levels of CAR. Furthermore, we show that
      PCI enables proper gene delivery of fiberless Ad5 at viral concentrations and
      infection times where transduction of photochemically untreated cells was
      negligible, both in the absence and presence of PLL. Thus, we conclude that the
      photochemically induced transduction by adenoviral vectors complexed with
      polycations present an opportunity to obtain high cell-infectivity levels with
      low viral doses, also without the fiber-CAR interaction.

PMID- 14712300
TI  - Effects of dose, intervention time, and radionuclide on sodium iodide symporter
      (NIS)-targeted radionuclide therapy.
AB  - The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is
      the molecular basis of thyroid radioiodine therapy. We previously have shown that
      NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and
      increased survival by radioiodine. In this study, we show that: (1) the
      therapeutic effectiveness of (131)I in prolonging the survival time of rats
      bearing F98/hNIS gliomas is dose- and treatment-time-dependent; (2) the number of
      remaining NIS-expressing tumor cells decreased greatly in RG2/hNIS gliomas post
      (131)I treatment and was inversely related to survival time; (3) 8 mCi each of
      (125)I/(131)I is as effective as 16 mCi (131)I alone, despite a smaller tumor
      absorbed dose; (4) (188)ReO(4), a potent beta(-) emitter, is more efficient than
      (131)I to enhance the survival of rats bearing F98/hNIS gliomas. These studies
      demonstrate the importance of radiopharmaceutical selection, dose, and timing of
      treatment to optimize the therapeutic effectiveness of NIS-targeted radionuclide
      therapy following gene transfer into gliomas.

PMID- 14712301
TI  - Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal
      sclerosis in a mouse model of scleroderma.
AB  - Systemic sclerosis (SSc) is a connective tissue disorder with an unknown
      etiology. There are currently no effective therapies for SSc. (In this study,
      working with a bleomycin(BLM)-induced scleroderma model mice, we performed two
      transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal
      muscle and showed that this treatment not only helped to prevent the dermal
      sclerosis simultaneously injected BLM but also improved the symptoms of dermal
      sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an
      immunohistochemical analysis revealed that both mRNA and protein of human HGF as
      well as murine HGF were enhanced in the skin, lung, muscle and the serum after
      two transfections of human HGF cDNA. These analyses also revealed that this
      treatment significantly reduced both the expression of the TGF-beta1 mRNA and the
      production of TGF-beta1 on macrophage-like cells that infiltrated the dermis and
      the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene
      transfection both prevented and ameliorated the symptoms of not only dermal
      sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection.
      These results indicated that gene therapy by the transfection of the human HGF
      cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.

PMID- 14712302
TI  - Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy
      prevents type I diabetes in NOD mice.
AB  - Type I diabetes results from an autoimmune destruction of the insulin-producing
      pancreatic beta cells. Although the exact immunologic processes underlying this
      disease are unclear, increasing evidence suggests that immunosuppressive,
      immunoregulatory and anti-inflammatory agents can interrupt the progression of
      the disease. Alpha 1 antitrypsin (AAT) is a multifunctional serine proteinase
      inhibitor (serpin) that also displays a wide range of anti-inflammatory
      properties. To test the ability of AAT to modulate the development of type I
      diabetes, we performed a series of investigations involving recombinant adeno
      associated virus vector (rAAV)-mediated gene delivery of human alpha-1
      antitrypsin (hAAT) to nonobese diabetic (NOD) mice. Recombinant AAV-expressing
      hAAT (rAAV2-CB-AT) was administered intramuscularly to 4-week-old female NOD mice
      (1 x 10(10) i.u./mouse). A single injection of this vector reduced the intensity
      of insulitis, the levels of insulin autoantibodies, and the frequency of overt
      type I diabetes (30% (3/10) at 32 weeks of age versus 70% (7/10) in controls).
      Transgene expression at the injection sites was confirmed by immunostaining.
      Interestingly, antibodies against hAAT were present in a majority of the vector
      injected mice and circulating hAAT was undetectable when assessed 10 weeks
      postinjection. This study suggests a potential therapeutic role for AAT in
      preventing type I diabetes as well as the ability of AAV gene therapy-based
      approaches to ameliorate disease effectively.

PMID- 14712303
TI  - Dominant-negative mutant of c-Jun gene transfer: a novel therapeutic strategy for
      colorectal cancer.
AB  - Activator protein-1 (AP-1), a transcription factor, is activated through many
      oncogenic signals. However, its biological role in colorectal cancer has not been
      fully elucidated. To investigate the role of AP-1 in colorectal cancer, we
      constructed an adenovirus-expressing TAM67, a dominant-negative mutant of c-Jun
      lacking the transactivation domain of wild c-Jun (DN-c-Jun), to inhibit
      endogenous AP-1. AP-1 DNA-binding activity was increased in colon cancer cells
      (HT-29 cells) by serum stimulation, followed by an increase in both
      [(3)H]thymidine incorporation and cell number. Transfection of Ad-DN-c-Jun to HT
      29 cells significantly inhibited serum-induced cell proliferation in vitro. As
      shown by flow cytometric analysis, DN-c-Jun significantly inhibited entrance into
      S phase after serum stimulation, thereby leading to G(1) arrest. In vivo
      transfection of Ad-DN-c-Jun into xenografted HT-29 cell tumors in nude mice
      significantly decreased tumor volume on day 21 after treatment. A change was
      associated with decrease in Ki-67 labeling index. These observations together
      showed that AP-1 is a critical modulator for proliferation and cell cycle of HT
      29 cells. We obtained the first evidence that DN-c-Jun gene transfer exerted a
      significant antitumor effect on colon cancer both in vitro and in vivo. DN-c-Jun
      gene transfer may be a new candidate for treatment of colorectal cancer.

PMID- 14712304
TI  - Dextran-spermine polycation: an efficient nonviral vector for in vitro and in
      vivo gene transfection.
AB  - Dextran-spermine cationic polysaccharide was prepared by means of reductive
      amination between oxidized dextran and the natural oligoamine spermine. The
      formed Schiff-base imine-based conjugate was reduced with borohydride to obtain
      the stable amine-based conjugate. The transfection efficiency of the synthetic
      dextran-spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found
      to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent.
      Modification of the dextran-spermine polycation with polyethylene glycol resulted
      in high transfection yield in serum-rich medium. Intramuscular injection in mice
      of dextran-spermine-pSV-LacZ complex induced high local gene expression compared
      to low expression of the naked DNA. Intravenous injection of a dispersion of the
      dextran-spermine-pSV-LacZ complex resulted with no expression in all examined
      organs. When the partially PEGylated dextran-spermine-pSV-LacZ complex was
      intravenously applied, a high gene expression was detected mainly in the liver.
      Preliminary targeting studies indicated that the PEGylated dextran-spermine-pSV
      LacZ complex bound to galactose receptor of liver parenchymal cells rather than
      the mannose receptor of liver nonparenchymal cells. This work offers a new
      biodegradable polycation based on natural components, which is capable of
      transfecting cells and tissues in vitro and in vivo.

PMID- 14712305
TI  - Intravenous administration of an AAV-2 vector for the expression of factor IX in
      mice and a dog model of hemophilia B.
AB  - Previous experiments have demonstrated the stable expression of factor IX (FIX)
      protein in mice and canine models of hemophilia B following portal vein gene
      transfer with a recombinant adeno-associated virus (rAAV) vector encoding FIX.
      Here, we present the results of studies that further optimized the rAAV vector
      transgene cassette used to express FIX and explored the use of the less-invasive
      intravenous (i.v.) route of vector administration for the treatment of hemophilia
      B. First, a liver-specific promoter was evaluated in conjunction with cis-acting
      regulatory elements in mice. Constructs that included both the beta-globin intron
      and the woodchuck hepatitis virus post-transcriptional regulatory element
      resulted in the highest level of FIX expression in vivo. Using this optimized
      vector, we demonstrate that i.v. injection was feasible for hepatic gene transfer
      in mice, achieving 70-80% of portal vein expression levels of FIX. In further
      studies using the Chapel Hill strain of hemophilia B dogs, we demonstrate for the
      first time FIX expression and partial correction of the bleeding disorder
      following i.v. administration of an AAV vector.

PMID- 14712306
TI  - Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's
      enhancement of viral oncolysis.
AB  - Oncolytic viruses (OVs) are being used as anticancer agents in preclinical and
      clinical trials. Propagation of OVs inside infected tumors is critical to their
      efficacy and is mediated by the productive generation of progeny OVs within
      infected tumor cells. In turn, this progeny can spread the infection to other
      tumor cells in successive rounds of oncolysis. Previously, we had found that, in
      rats, cyclophosphamide (CPA) pretreatment increased infection of brain tumors by
      an intra-arterially administered herpes simplex virus type 1 OV, because it
      inhibited activation of complement responses, mediated by innate IgM. We also
      have previously shown that other pharmacologic inhibitors of complement, such as
      cobra venom factor (CVF), allowed for increased infection. However, in these
      studies, further inhibition of complement responses by CVF did not result in
      additional infection of brain tumor cells or in propagation of OV to surrounding
      tumor cells. In this study, we sought to determine if CPA did lead to increased
      infection/propagation from initially infected tumor cells. Unlike our results
      with CVF, we find that CPA administration does result in a time-dependent
      increase in infection of tumor cells, suggestive of increased propagation, in
      both syngeneic and athymic models of brain tumors. This increase was due to
      increased survival of OV within infected tumors and brain surrounding tumors.
      CPA's effect was not due to a direct enhancement of viral replication in tumor
      cells, rather was associated with its immunosuppressive effects. RT-PCR analysis
      revealed that CPA administration resulted in impaired mRNA production by
      peripheral blood mononuclear cells (PBMCs) of several cytokines (interferons
      alpha/beta, interferon gamma, TNFalpha, IL-15, and IL-18) with anti-HSV function.
      These findings suggest that the CPA-mediated facilitation of OV intraneoplastic
      propagation is associated with a general decrease of antiviral cytokines mRNAs in
      PBMCs. These findings not only suggest a potential benefit for the addition of
      transient immunosuppression in clinical applications of oncolytic HSV therapy,
      but also suggest that innate immunomodulatory pathways may be amenable to
      manipulation, in order to increase OV propagation and survival within infected
      tumors.

PMID- 14712307
TI  - Stable transfection of MSCs by electroporation.
AB  - Human marrow stromal cells (hMSCs) are an attractive source of adult stem cells
      for autologous cell and gene therapy. To transfect hMSCs without the use of
      viruses, we developed improved conditions for stable transfection of the cells by
      electroporation. hMSCs were isolated by adherence to plastic, and were
      electroporated at 600 V and 100 micros in a 2-mm gap cuvette with a plasmid
      containing enhanced green fluorescence protein (EGFP) and neomycin
      phosphotransferase gene (neo(r)). After electroporation of 10(6) cells with 10
      microg of the linearized plasmid DNA, hMSCs with stable DNA integration were
      selected by culturing with 200 microg/ml G418. The transfected hMSCs were
      expanded another 300-fold in 14 days to obtain 89 million cells, of which 98%
      expressed EGFP. Chloroquine increased the number of hMSCs transiently expressing
      EGFP from 12% to over 50%, but decreased stable integration. Stable integration
      of plasmid DNA into rat MSCs by electroporation was also successful. The
      transfected MSCs retained their capacity to differentiate into both adipocytes
      and osteoblasts. Thus, MSCs were stably transfected with plasmid DNA and retained
      their differentiation capacity after expansion.

PMID- 14712308
TI  - Genetic association of coeliac disease susceptibility to polymorphisms in the
      ICOS gene on chromosome 2q33.
AB  - An interesting candidate gene region for coeliac disease (CD), a common
      multifactorial disease, is a segment on 2q33-37 harbouring the genes for the
      CD28, cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), inducible costimulator
      (ICOS), and programmed death-1 (PD-1), all receptors that regulate lymphocyte
      activation. Several studies have suggested a role for this locus in immune
      mediated diseases. To study further our previous finding of genetic linkage of
      this region to CD, we studied 25 polymorphic markers to identify the putative
      disease-associated polymorphism. Transmission/disequilibrium test in 106 Finnish
      families with CD indicated that only four polymorphisms, all located in the ICOS
      gene, showed evidence for genetic association. Strong linkage disequilibrium
      (LD), based on the analysis of 424 haplotypes, encompassed not only the
      associated ICOS markers but also many polymorphisms in the CTLA4 gene. Our
      results demonstrate that due to LD, it appears not easy to identify the genuine
      susceptibility factor in this region without larger multipopulation studies.
      Furthermore, the results did not support the evidence that polymorphisms in CTLA4
      were the major susceptibility locus for CD.

PMID- 14712309
TI  - Polymorphisms in the interleukin-20 gene: relationships to plaque-type psoriasis.
AB  - We analyzed the frequency of single-nucleotide polymorphisms (SNPs) at positions 
      1053 (rs 2981572), 1380 (rs 2981573), 1462 (rs 2232360), and 3978 (rs 1518108) of
      the human interleukin-20 (IL-20) gene by tetraprimer ARMS-PCR method. A
      significant association between patients with psoriasis and the G allele at
      position -1053 (P<0.05) was established. The pairwise linkage disequilibrium (LD)
      matrix showed that the nearly complete LD was present within the polymorphisms at
      positions -1053, 1380, and 1462 of the IL-20 gene. We found that patients with
      plaque psoriasis had a higher frequency of the HT3 GAA haplotype (P<0.01, OR
      2.341, 95% CI: 1.346-4.074) compared to the control group. Likewise, the HT3 GAA
      haplotype was associated with an increased risk of early-onset psoriasis (P<0.01,
      OR 2.305, 95% CI: 1.285-4.132), late onset of disease (P<0.01, OR 2.542, 95% CI:
      1.266-5.102), familial psoriasis (P<0.02, OR 2.220, 95% CI: 1.249-3.945), and
      sporadic disease (P<0.01, OR 2.523, 95% CI: 1.390-4.580). Our data indicate that
      IL-20 gene polymorphisms should have a role in determining susceptibility to
      plaque-type psoriasis. The possible role of the studied SNPs in the regulation of
      the expression of IL-20 is unknown yet and needs further studies.

PMID- 14712310
TI  - Analysis of IL4R haplotypes in predisposition to multiple sclerosis.
AB  - We have investigated the association of multiple sclerosis (MS) with
      polymorphisms in the IL4R gene in 332 single-case MS families. IL4R encodes a
      subunit of the interleukin-4 receptor, a molecule important for T-cell
      development and differentiation, and is a gene shown to be associated with immune
      related diseases such as asthma and type I diabetes. By genotyping two promoter
      and eight coding IL4R SNPs and identifying haplotypes (complex alleles) in the MS
      families, stratified for HLA genotype, we have observed evidence of the
      association of the IL4R gene to MS. In particular, we have identified a specific
      susceptibility haplotype, and observe that the risk is conferred primarily to
      individuals not carrying the high MS-risk HLA DR2 (DRB1(*)1501-DQB1(*)0602)
      haplotype (nominal P=0.009). These findings suggest a potentially important role
      for the IL4R gene in predisposition to MS, and provide further evidence of its
      relevance as a candidate gene for immune-related diseases.

PMID- 14712311
TI  - Association of matrix metalloproteinase 3 promoter genotype with disease outcome
      in rheumatoid arthritis.
AB  - Matrix metalloproteinases (MMPs) are implicated in joint destruction in
      rheumatoid arthritis (RA). We investigated whether the 5A/6A polymorphism within
      the MMP-3 (stromelysin-1) gene promoter region is associated with disease outcome
      in 254 patients with established RA. Patients homozygous for the MMP-3 6A allele
      had more radiographic damage (measured by Larsen score) than those with other
      genotypes (109.8 vs 91.1, P=0.04). Patients with the 6A/6A genotype also had more
      functional impairment and higher serum proMMP-3 levels, although only the latter
      was significant (P=0.002). A possible association was found between homozygosity
      for the 6A allele and carriage of the RA-associated HLA-DRB1 shared epitope (SE).
      Combination of these factors was associated with more severe disease than the SE
      alone. The data suggest that the MMP-3 6A/6A genotype is associated with worse RA
      outcome, and that this genotype may have an additive effect with the SE on
      disease severity.

PMID- 14712312
TI  - Antiproliferative activity of G-quartet-containing oligonucleotides generated by
      a novel single-stranded DNA expression system.
AB  - Recently, a novel single-stranded DNA (ssDNA) expression system that can generate
      intracellularly ssDNA or oligodeoxynucleotide (ODN) molecules has been developed.
      Previous studies showed that this ssDNA expression system is capable of
      generating DNA enzyme ODNs and triplex-forming oligodeoxynucleotides (TFOs) in
      cells. In this study, we constructed an ssDNA expression vector that can generate
      a G-quartet-containing ODNs, GRO29A, in cells. Similar to synthetic ODNs, vector
      generated GRO29As were shown to have significant antiproliferative activities in
      a number of cancer cell lines. These results further demonstrate the potential
      application of ssDNA expression system in gene target validation and drug
      development.

PMID- 14712313
TI  - Vaccine-induced CD8+ T cells eliminate tumors by a two-staged attack.
AB  - Data presented here demonstrate that vaccine-induced CD8(+) T cells can eliminate
      their specific tumor-target with a two-staged attack. First, they release
      interferon-gamma that results in growth arrest of the tumor cells via induction
      of antiangiogenic mediators. Then, during the latter stages of the immune
      response, CD8(+) effector T cells eradicate the remaining tumor cells through
      perforin-mediated lysis. A combination of these two mechanisms is highly
      effective in the described model, while either pathway alone fails to completely
      achieve tumor rejection.

PMID- 14712314
TI  - Inhibition of K562 leukemia angiogenesis and growth by expression of antisense
      vascular endothelial growth factor (VEGF) sequence.
AB  - Vascular endothelial growth factor (VEGF), a major angiogenic factor, plays a key
      role in the growth of solid tumor. Recently, expression of VEGF and its receptors
      has been found on leukemic cells as well as on endothelial cells. VEGF may
      fulfill a fundamental role in promoting tumor angiogenesis and proliferation by
      stimulating both endothelial cells and leukemic cells. To investigate the role of
      VEGF in the angiogenesis and growth of leukemic cell, we used an antisense
      strategy to downregulate VEGF expression in K562 cells, a human erythroleukemia
      cell line. Expression of antisense-VEGF in K562 cells reduced the secretion of
      VEGF protein and inhibited cell survival. The proliferation and migration of
      human umbilical vein endothelial cells were decreased in response to the
      conditioned medium (CM) from K562 cells expressed antisense-VEGF, compared to CM
      from K562 cells transfected with vector control. Moreover, subcutaneous injection
      of nude mice with antisense-VEGF K562 cells inhibited tumor growth with a
      reduction of the density of microvessels and an increased apoptosis in those
      tumors, compared to vector control K562 cells. These results suggest that the
      efficient downregulation of the VEGF production in leukemic cells using antisense
      VEGF may constitute a novel strategy of treatment in leukemia.

PMID- 14712315
TI  - Complete tumor prevention by engineered tumor cell vaccines employing nonviral
      vectors.
AB  - We report that 100% mice survival after tumor challenge is achieved with cytokine
      engineered cells employing nonviral lipoplexes and without using viral vectors.
      We describe this effect with cytokine-secreting tumor cell vaccines, based on
      cell clones or fresh transfected cells. Tumor cells were transfected with murine
      granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-4 plasmids
      employing the cationic lipid DOTAP, were irradiated (150 Gy) and kept frozen
      until use. The transfection efficacy was analyzed by qRT-PCR and flow cytometry.
      Vaccination induced potent antitumor rejection, resulting in 100% mice survival.
      Furthermore, the antitumor immunity was long lasting, since a two-fold survival
      delay was observed in mice after tumor rechallenge (6 months later). While cell
      clones secreting GM-CSF were the most effective in wild-type tumor cell
      rejection, little or no effect was observed with clones secreting IL-4. We found
      similar antitumor efficacy employing fresh transfected cells by nonviral
      procedures, demonstrating that cells genetically modified by nonviral vectors
      (both clones and fresh transfected cells) are a safe and efficient tool for
      antitumor vaccines. These vaccines allow us to achieve the highest antitumor
      efficacy based on nonviral gene therapy techniques. In addition, the vaccination
      success with fresh transfected cells simplifies the procedure and provides new
      insights into the clinical application of nonviral gene therapy procedures.

PMID- 14712316
TI  - Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a
      recombinant adeno-associated virus type-2 vector.
AB  - In this study, we elucidated the potential of recombinant adeno-associated virus
      type-2 (rAAV-2) vectors for lung cancer gene therapy. Cell lines of the three
      major histological subtypes of non-small cell lung cancer (NSCLC) were highly
      susceptible for rAAV-2 showing transduction rates between 63.4 and 98.9%. In
      contrast, cell lines of small cell carcinomas were resistant to rAAV-2 infection.
      For restoration of p53 function in p53 deficient NSCLC, a rAAV-2 vector was
      constructed containing wt p53 cDNA. Following transduction with rAAV-p53, cell
      growth of all NSCLC cell lines was significantly reduced in a dose-dependent
      manner between 44 and 71.7% in comparison with rAAV-GFP transduced cells. The
      reduction of tumor cell growth was associated with increased apoptosis. Adding
      cisplatin to rAAV-p53-infected cells led to a significant growth inhibition
      between 81 and 91% indicating a synergistic effect between cisplatin and rAAV
      p53. Interestingly, the tumor cells surviving cisplatin and rAAV-p53 treatment
      were inhibited in their ability to form colonies as reflected by a reduction of
      colony growth between 57 and 90.4%. In conclusion, rAAV-2 vectors exhibit a
      strong tropism for NSCLC. Successful inhibition of tumor cell growth following
      transduction with a rAAV-p53 vector underlines the potential role of rAAV-2 in
      cancer gene therapy.

PMID- 14712317
TI  - Human dendritic cells genetically engineered to express cytosolically retained
      fragment of prostate-specific membrane antigen prime cytotoxic T-cell responses
      to multiple epitopes.
AB  - The ability of two plasmid DNA vaccines to stimulate lymphocytes from normal
      human donors and to generate antigen-specific responses is demonstrated. The
      first vaccine (truncated; tPSMA) encodes for only the extracellular domain of
      prostate-specific membrane antigen (PSMA). The product, expressed following
      transfection with this vector, is retained in the cytosol and degraded by the
      proteasomes. For the "secreted" (sPMSA) vaccine, a signal peptide sequence is
      added to the expression cassette and the expressed protein is glycosylated and
      directed to the secretory pathway. Monocyte-derived dendritic cells (DCs) are
      transiently transfected with either sPSMA or tPSMA plasmids. The DCs are then
      used to activate autologous lymphocytes in an in vitro model of DNA vaccination.
      Lymphocytes are boosted following priming with transfected DCs or with peptide
      pulsed monocytes. Their reactivity is tested against tumor cells or peptide
      pulsed T2 target cells. Both tPSMA DCs and sPSMA DCs generate antigen-specific
      cytotoxic T-cell responses. The immune response is restricted toward one of the
      four PSMA-derived epitopes when priming and boosting is performed with sPSMA. In
      contrast, tPSMA-transfected DCs prime T cells toward several PSMA-derived
      epitopes. Subsequent repeated boosting with transfected DCs, however, restricts
      the immune response to a single epitope due to immunodominance.

PMID- 14712318
TI  - Heat shock protein 70 gene therapy combined with hyperthermia using magnetic
      nanoparticles.
AB  - Heat shock proteins (HSPs) are recognized as significant participants in immune
      reactions. We previously reported that expression of HSP70 in response to
      hyperthermia, produced using our original magnetite cationic liposomes (MCLs),
      induces antitumor immunity. In the present study, we examine whether the
      antitumor immunity induced by hyperthermia is enhanced by hsp70 gene transfer. A
      human hsp70 gene mediated by cationic liposomes was injected into a B16 melanoma
      nodule in C57BL/6 mice in situ. At 24 hours after the injection of the hsp70
      gene, MCLs were injected into melanoma nodules in C57BL/6 mice, which were
      subjected to an alternating magnetic field for 30 minutes. The temperature at the
      tumor reached 43 degrees C and was maintained by controlling the magnetic field
      intensity. The combined treatment strongly arrested tumor growth over a 30-day
      period, and complete regression of tumors was observed in 30% (3/10) of mice.
      Systemic antitumor immunity was induced in the cured mice. This study
      demonstrates that this novel therapeutic strategy combining the use of hsp70 gene
      therapy and hyperthermia using MCLs may be applicable to patients with advanced
      malignancies.

PMID- 14712319
TI  - Increased radiation-induced apoptosis and altered cell cycle progression of human
      lung cancer cell lines by antisense oligodeoxynucleotides targeting p53 and
      p21(WAF1/CIP1).
AB  - Lung cancer is difficult to control locally by radiotherapy and is known to have
      frequently p53 mutations. Previous results have shown that non-small-cell lung
      cancer (NSCLC) cell lines with nonfunctional p53 have a higher fraction of
      radiation-induced apoptosis and that apoptosis follows after the release from the
      G2/M arrest. The aim of the present work was to study whether inhibition of the
      p53 response in NSCLC cell lines can modulate the G2/M arrest and the induction
      of apoptosis after ionizing radiation. Antisense oligodeoxynucleotides (As-ODNs)
      were used to inhibit the p53 response in the cell lines H460 and A549 with
      functional p53. In addition, H661 with nonfunctional p53 was used. The results
      have shown that As-ODNs targeting mRNA of p53 and p21 downregulate radiation
      induced expression of p53 and p21(WAF1/CIP1). Delayed apoptosis (35.7+/-4.2% in
      H460, 1.2+/-0.4% in A549 and 72.2+/-6.5% in H661) was observed after cell cycle
      progression beyond the G2 block, either in the late G2 phase of the same cell
      cycle being irradiated (H661) or in the G1 phase of the subsequent cell cycle
      (H460, A549). As-p53 significantly decreased the fraction of G2/M-arrested cells
      in H460 cells and increased radiation-induced apoptosis at 96 hours by 17.9+/-8.5
      and 9.1+/-3.3% to 53.6+/-7.4 and 10.8+/-2.9% in H460 and A549 cells (P<.01),
      respectively, but had no effect in H661 cells with nonfunctional p53. In
      addition, As-p21 decreased the fraction of G2-arrested A549 and H460 cells and
      increased apoptosis by 23.8+/-5.2 and 31.6+/-7.3% to 59.4+/-3.1 and 32.8+/-7.3%,
      respectively (P<.01). In conclusion, these data show that radiation-induced G2
      arrest is decreased in NSCLC cells and radiation-induced apoptosis is increased
      when p53-responsive pathways are blocked via As-ODN targeting p53 or
      p21(WAF1/CIP1) mRNA. In view of the fact that p53 and p21 As-ODN had similar
      effects on radiation-induced apoptosis normalized by their ability to inhibit
      radiation-induced p21 expression, we concluded that p21 is an important trigger
      of late ionizing radiation-induced apoptosis.

PMID- 14712320
TI  - Potential drug interaction between simvastatin and danazol causing
      rhabdomyolysis.
AB  - Rhabdomyolysis is a life-threatening clinical and biochemical syndrome that
      results from injury to skeletal muscle. Hydroxymethylglutaryl coenzyme A
      reductase inhibitors (statins) have been associated with myopathy and
      rhabdomyolysis. Although rhabdomyolysis is a rare adverse event associated with
      this class of drugs, their prevalent use in the management of dyslipidemia makes
      it increasingly important for clinicians to understand the nature of this
      condition. Rhabdomyolysis can occur with all statins when used alone and
      particularly when combined with other drugs that are themselves myotoxic or that
      elevate the concentration of the statin. Statins are particularly susceptible to
      the latter effect because of their metabolism by the CYP450 system and their low
      oral bioavailability. In this report, we describe a case of rhabdomyolysis and
      acute renal failure secondary to the interaction between danazol and simvastatin.

PMID- 14712321
TI  - Trimethoprim-sulfamethoxazole-associated hepatotoxicity - part of a
      hypersensitivity syndrome.
AB  - Trimethoprim-sulfamethoxazole is a commonly used medication. Side effects are
      numerous and include drug hypersensitivity syndrome. The case of a 24-year-old
      woman with severe liver failure is presented. Erythema multiforme and
      thrombocytopenia developed after the acute onset of hepatotoxicity and after all
      medications had been stopped. Clinical resolution of all features occurred over
      weeks but laboratory abnormalities persisted up to eight months later. A causal
      link with sulfamethoxazole was supported by timing, liver biopsy and lymphocyte
      toxicity test. This case illustrates one presentation and the possible severity
      of the drug hypersensitivity syndrome associated with trimethoprim
      sulfamethoxazole.

PMID- 14712322
TI  - The safety of oral hypoglycemic agents in the first trimester of pregnancy: a
      meta-analysis.
AB  - OBJECTIVE: To examine the relationship between first-trimester exposure to oral
      hypoglycemic agents (OHAs), congenital anomalies and neonatal mortality,
      accounting for the potential confounding effect of maternal glycemic control.
      METHOD: A meta-analysis was conducted by searching the literature for studies
      reporting on women with type II diabetes mellitus, first-trimester exposure to
      OHAs and either major malformations and/or neonatal mortality. Glycemic control
      monitoring was noted. Studies were reviewed by two reviewers and disagreement was
      resolved by consensus. Odds ratios and risk differences were calculated to
      determine the risk of major malformations and neonatal mortality between those
      exposed and those not exposed to OHAs. RESULTS: Ten studies met the inclusion
      criteria. There was no significant difference in the rates of major malformations
      between those exposed and those not exposed to OHAs; the odds ratio was 1.05 (95%
      CI 0.65 to 1.70) and the risk difference was 0.00 (95% CI -0.03 to 0.03). For
      studies reporting glycemic control, the odds ratio for major malformations
      between those exposed and those not exposed to OHAs was 1.06 (95% CI 0.62 to
      1.81). For neonatal death, the odds ratio was 1.16 (95% CI 0.67 to 2.00) and the
      risk difference was -0.03 (95% CI -0.17 to 0.12). The studies did not provide
      sufficient detail to determine which OHA(s) were associated with adverse neonatal
      outcomes. CONCLUSIONS: First-trimester exposure to OHAs did not significantly
      increase rates of major malformations or neonatal death. However, the studies
      were heterogeneous and care must be taken in interpreting the results. Further
      studies are needed to address the safety of OHAs in the first trimester with
      concomitant good glycemic control.

PMID- 14712323
TI  - Thiamine deficiency in congestive heart failure patients receiving long term
      furosemide therapy.
AB  - OBJECTIVE: To assess the presence of thiamine deficiency in congestive heart
      failure patients receiving furosemide therapy. DESIGN: Prospective, biochemical
      analysis of thiamine status was performed in outpatients and inpatients of the
      University of Ottawa Heart Institute. SUBJECTS: Thirty-two patients with
      congestive heart failure who received at least 40 mg/day of furosemide were
      included. Patients were then separated into two groups depending on whether the
      dose of furosemide was greater than or equal to 80 mg/day. METHODS: The primary
      measure was actual thiamine status as assessed by the erythrocyte transketolase
      enzyme activity and the degree of thiamine pyrophosphate effect. RESULTS:
      Biochemical evidence of severe thiamine deficiency was found in 98% (24 of 25)
      patients receiving at least 80 mg/day of furosemide and in 57% (four of seven) of
      patients taking 40 mg furosemide daily, odds ratio (OR) 19.0 (1.13<OR<601.29).
      Thiamine status was not associated with any other clinical variables.
      CONCLUSIONS: These findings suggest that thiamine deficiency occurs in a
      substantial proportion of congestive heart failure patients being treated with
      furosemide.

PMID- 14712324
TI  - Challenges of adherence management in human immunodeficiency virus
      pharmacotherapy.
AB  - Medication adherence to highly active antiretroviral therapy (HAART) is currently
      a topic of major importance in human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome care. HAART has dramatically reduced morbidity and
      mortality from HIV infection. Many people with HIV now live active and productive
      lives, with the disease itself having minimal impact on their lifespan. Unlike
      treatment for other chronic diseases, achieving the full benefit of HAART
      requires an extremely high level of adherence to potent antiretroviral
      combinations that is often difficult to achieve given the high pill burdens, drug
      interactions and adverse events associated with treatment. In this paper, the
      present knowledge regarding antiretroviral medication adherence is summarized
      with a focus on understanding the importance of adherence, the relationship
      between adherence and treatment response, the challenges and barriers facing
      patients trying to achieve optimal adherence, reasons for nonadherence, and the
      current directions and issues relevant to future adherence research.

PMID- 14712325
TI  - Stroke prevention in hospitalized patients with atrial fibrillation: a population
      based study.
AB  - BACKGROUND: Oral anticoagulants reduce the incidence of stroke by 68%, yet
      suboptimal use has been documented in surveys of patients with atrial
      fibrillation. The present study examined current patterns of anticoagulant use
      for patients hospitalized with atrial fibrillation across an entire health care
      system. METHODS: Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a
      prospective cohort study involving all patients hospitalized in Nova Scotia with
      atrial fibrillation, among other conditions. Consecutive inpatients with atrial
      fibrillation from October 15, 1997 to October 14, 1998 were studied. Detailed
      demographic and clinical data were collected and the proportion of patients using
      antithrombotic therapy was tabulated by risk category. Multivariate logistic
      regression was used to assess the relationship of various demographic and
      clinical factors with the use of antithrombotic agents. RESULTS: There were 2202
      patients hospitalized with atrial fibrillation; 644 admitted specifically for
      this condition. Only 21% of patients admitted with atrial fibrillation were on
      warfarin sodium at admission and this increased by time of discharge. Diabetes
      was negatively correlated with warfarin sodium use. Histories of prosthetic valve
      replacement, stroke/transient ischemic attack, and heart failure were positively
      associated with anticoagulant use on admission. Patients with prosthetic valve
      replacement, heart failure, or hyperlipidemia were most likely to receive
      anticoagulants at discharge. CONCLUSION: Antithrombotic agents remain underused
      by patients with atrial fibrillation. While higher risk patients are generally
      targeted, this is not invariably the case; thus, diabetics remain under treated.
      Further work is needed to explain such anomalous practice and promote optimal
      antithrombotic therapy use.

PMID- 14712326
TI  - Can continuing benzodiazepine use be predicted?
AB  - The objective of the present study was to examine characteristics of
      benzodiazepine (BZD) users, as well as try to identify predictors of continuing
      BZD use. Health-related data were collected twice on the same sample of Canadians
      two years apart. Drug use was based on the question: "What medications did you
      take over the last two days?" while other variables used were age, sex,
      education, marital status, chronic conditions, non-BZD drug use, health status
      and pain level. Of the 11,624 respondents, 371 (3.2%) reported taking BZDs in
      1994. Logistic regression results showed that the highest odds of BZD use were
      for antidepressant users (OR=10.7, P<0.05), followed by poor health (OR=5.0,
      P<0.05), pain (OR=3.9, P<0.05) and chronic conditions (OR=3.2, P<0.05). Of the
      371 individuals who reported BZD use in 1994, 198 (53.4%) reported BZD use in
      1996. Logistic regression showed that none of the variables mentioned above
      showed a significant association with continuing (including gaps in use) BZD use
      in 1996. Regarding individual BZDs, it could not be concluded definitively that
      any BZD is more likely to show continued use than any other, but the possibility
      of a linear relationship between the proportion of continued use and the half
      life of the BZD should be investigated further. Thus, the main predictive factor
      for continuing use of BZD, as shown by this study, is that of previous use.
      Whenever a BZD is prescribed, regardless of whether it is a new or repeat
      prescription, it should be remembered that the likelihood of continuing use is
      considerable.

PMID- 14712327
TI  - Need for an improved submission process for listing drugs for reimbursement in
      Canadian provinces.
AB  - BACKGROUND: To have a drug listed in a province's formulary, manufacturers must
      submit an application providing data required by the provincial rules and
      guidelines. The procedures for the scientific evaluation of drugs considered for
      listing for reimbursement in five provinces have been examined previously.
      OBJECTIVE: The present study investigates the clarity of the same five provinces'
      rules and guidelines about effectiveness and cost data that should be included in
      listing submissions from the perspective of the pharmaceutical company. METHODS:
      The manufacturers of five recently introduced drugs selected by the investigators
      received questionnaires asking about the departments within their companies that
      are responsible for the submission, the data required by each of the five
      provinces and the clarity of each province's requirements for submission. Each
      company was also asked similar questions about its own submission experience with
      its drug. Investigators visited each manufacturer to review the questionnaires
      and answer questions. RESULTS: The manufacturers perceived the rules and
      guidelines on effectiveness and economic data of several provinces as being
      neither clear nor consistent. Consequently, information that companies submit in
      their attempts at compliance with the rules and guidelines varies substantially.
      CONCLUSIONS: The manufacturers' perceptions of the information required by the
      provinces on effectiveness and cost information were inconsistent. Previous work
      indicated that the provinces make significant decisions about listings based on
      inadequate information resulting in a scientifically flawed system that
      contributes to considerable inequality in access to new drugs between provinces.
      The findings of the present work reinforce this conclusion.

PMID- 14712328
TI  - Haemoglobin function and respiratory status of the Port Jackson shark,
      Heterodontus portusjacksoni, in response to lowered salinity.
AB  - Haemoglobin function and respiratory status of sub-adult sharks, Heterodontus
      portusjacksoni was investigated for up to 1 week following transfer from 100% to
      either 75% or 50% seawater. Metabolic rates were unusually low and arterial
      venous differences in blood O2 small. Haemodilution from osmotic inflow lowered
      haematocrit and reduced blood O2 content by up to 50%. There was no change in O2
      consumption rate, blood O2 partial pressure, cardiac output, or the arterial
      venous O2 content difference, and thus O2 delivery was maintained. Ventilation
      was acutely elevated but returned to normal within 24 h. The O2 delivery to the
      tissues was facilitated by decreased blood O2-affinity that could not be simply
      ascribed to changes in the osmolyte concentration. The Hb was unaffected by
      changes in intra-erythrocyte fluid urea or trimethylamine-N-oxide (TMAO) but was
      sensitive to changes in NaCl. The Bohr shifts in whole blood were low and there
      was little role for pH in modulating O2 transport. Venous Hb saturation remained
      close to 65%, at the steepest part of the in vivo O2 equilibrium curve, such that
      O2 unloading could be facilitated by small reductions in pressure without
      increasing cardiac or ventilatory work. H. portusjacksoni tolerated 50% seawater
      for at least 1 month, but there was little evidence of respiratory responses
      being adaptive which instead appeared to be consequential on changes in osmotic
      and ionic status.

PMID- 14712329
TI  - Distribution and properties of arginase in the salivary glands of four species of
      laboratory mammals.
AB  - Important progress in arginine metabolism includes the discovery of widespread
      expression of two isoforms of arginase, arginase I and II, not only in hepatic
      cells but also in non-hepatic cells, and the formation of nitric oxide, a widely
      distributed signal-transducing molecule, from arginine by nitric oxide synthase.
      Possible physiological roles of arginase may therefore include regulation of
      nitric oxide synthesis through arginine availability for nitric oxide synthase.
      In this paper, arginase was investigated in the submandibular, sublingual, and
      parotid glands of rat, mouse, guinea pig, and rabbit. From their arginase
      contents, the salivary glands of these species were divided into two groups.
      Variable levels of arginase activity were detected in the salivary glands of
      mouse and rat. However, salivary glands of rabbit and guinea pig had almost no
      arginase activity. The presence of nitric oxide synthase has been reported in all
      the salivary glands used in this study. Therefore, one of the important findings
      was the presence of species specificity in the co-localization of arginase and
      nitric oxide synthase in the salivary glands of the four species. The highest
      specific activity of arginase was found in mouse parotid gland. In rat,
      considerable arginase activity was detected in all three glands, at 3.6-7.3% of
      that in rat liver. In rat submandibular gland, arginase was detected in both
      cytosolic and particulate fractions. In addition, arginase was detected in
      isolated acinar cells, but not in duct cells. Experiments on the intracellular
      distribution and the effects of the arginase inhibitors ornithine and N(omega)
      hydroxy-L-arginine (NOHA), suggested the presence of both arginase I and arginase
      II in rat submandibular gland.

PMID- 14712330
TI  - A case of familial Mediterranean fever and polyarteritis nodosa complicated by
      spontaneous perirenal and subcapsular hepatic hemorrhage requiring multiple
      arterial embolizations.
AB  - The association of familial Mediterranean fever (FMF) and polyarteritis nodosa
      (PAN) has been well established. These patients have been reported to have an
      overall better prognosis than other PAN patients. Herein we report a patient with
      FMF and PAN who died of sepsis following a severe course of recurrent bleeding
      episodes which required multiple embolization attempts. The 39-year-old Turkish
      male presented with abdominal pain of 1-month duration. He had been diagnosed
      with FMF at the age of 24. On admission, he had pallor with general ill
      appearance. Rebound tenderness was obtained in the right upper abdominal
      quadrant. He had mild anemia, leukocytosis, thrombocytosis, and hypoalbuminemia.
      On the 2nd day of his admission, he developed hypotension with a rapid decline in
      hemoglobin level. Abdominal angiography showed multiple aneurysms in the branches
      of renal arteries, superior mesenteric artery, and hepatic arterial system
      including left renal infarct, suggesting PAN. He was put on high-dose steroids
      and oral cyclophosphamide. Despite medical treatment, he developed intense
      abdominal pain, hypotension, tachycardia, and a rapid fall in hemoglobin on four
      occasions. Active bleeding sites were embolized in two different angiography
      sessions. Although the patient experienced no more recurrent bleeding, he died of
      multiorgan dysfunction syndrome resulting from sepsis 6 weeks after admission.
      Polyarteritis nodosa associated with FMF may follow a grave course despite
      immunosuppressive therapy. Arterial embolization should be considered in the
      presence of bleeding aneurysms in addition to immunosuppressive therapy.

PMID- 14712331
TI  - Sequence, evolution and ligand binding properties of mammalian Duffy
      antigen/receptor for chemokines.
AB  - The Duffy antigen/ receptor for chemokine, DARC, acts as a widely expressed
      promiscuous chemokine receptor and as the erythrocyte receptor for Plasmodium
      vivax. To gain insight into the evolution and structure/function relations of
      DARC, we analyzed the binding of anti-human Fy monoclonal antibodies (mAbs) and
      human chemokines to red blood cells (RBCs) from 11 nonhuman primates and two
      nonprimate mammals, and we elucidated the structures of the DARC genes from
      gorilla, gibbon, baboon, marmoset, tamarin, night monkey and cattle. CXCL-8 and
      CCL-5 chemokine binding analysis indicated that the promiscuous binding profile
      characteristic of DARC is conserved across species. Among three mAbs that
      detected the Fy6 epitope by flow cytometric analysis of human and chimpanzee
      RBCs, only one reacted with night monkey and squirrel monkey. Only chimpanzee
      RBCs bound a significant amount of the anti-Fy3 mAb. Fy3 was also poorly detected
      on RBCs from gorilla, baboon and rhesus monkey, but not from new world monkeys.
      Alignment of DARC homologous sequences allowed us to construct a phylogenetic
      tree in which all branchings were in accordance with current knowledge of primate
      phylogeny. Although DARC was expected to be under strong internal and external
      selection pressure, in order to maintain chemokine binding and avoid Plasmodium
      vivax binding, respectively, our present study did not provide arguments in favor
      of a selection pressure on the extracellular domains involved in ligand
      specificity. The amino acid variability of DARC-like polypeptides was found to be
      well correlated with the hydrophilicity indexes, with the highest divergence on
      the amino-terminal extracellular domain. Analysis of the deduced amino acid
      sequences highlighted the conservation of some amino acid residues, which should
      prove to be critical for the structural and functional properties of DARC.

PMID- 14712333
TI  - Human handedness: is there a difference in the independence of the digits on the
      preferred and non-preferred hands?
AB  - In non-human primates, comparative studies show that greater dexterity is
      associated with greater independent control over the digits. Studies of humans,
      however, show no difference in the degree of independent control of single digits
      on the more dexterous preferred hand and its less dexterous partner. We wondered
      whether there might be a difference in the degree of independent control on the
      two hands during performance of functionally relevant tasks. Many object
      manipulation tasks require the ability to produce and control forces with more
      than one finger at the same time. We hypothesized that asymmetrical independence,
      with greater independence on the preferred than the non-preferred hand, would be
      evident with a task that requires the simultaneous production of force in two
      digits. We examined digit individuation when subjects produced flexion forces
      with a single digit in isolation, and simultaneous flexion forces in all ten
      combinations of two digits. Consistent with previous studies, we found no
      difference between the individuation of the digits on the preferred and non
      preferred hands during force production with single digits in isolation.
      Similarly, no asymmetry was present when forces were produced by two digits.
      However, separation of two-digit forces into thumb-to-digit opposition forces and
      non-opposition forces showed that although there was no difference in
      individuation between the two hands for non-opposition forces, the digits on the
      preferred hand were more independent than those on the non-preferred hand for
      opposition forces. We suggest that this independence asymmetry is not itself the
      underlying cause of the dexterity differences between the hands, but rather
      arises from a difference in the capacity for use-dependent reorganization of the
      motor cortical circuits controlling each hand, and that this difference might
      underlie the dexterity differences between the hands.

PMID- 14712334
TI  - Response to flumazenil in the late luteal phase and follicular phase of the
      menstrual cycle in healthy control females.
AB  - RATIONALE: Animal studies of short-term progesterone administration and
      withdrawal model the natural increase and abrupt decrease in progesterone levels
      which occur in the late luteal phase (LP) of the human menstrual cycle (MC).
      Previously, studies in animals have shown that abrupt cessation of chronic or
      short-term progesterone administration results in pharmacological changes at the
      GABAA receptor, resulting in altered sensitivity to GABAA receptor
      neuromodulators such as benzodiazepines and flumazenil, a GABAA receptor
      antagonist. OBJECTIVES: This study's goal was to compare the response to
      flumazenil in the follicular phase (FP) and late LP in female healthy controls
      (HCs). We postulated that HC females would exhibit a greater psychological and
      somatic response to flumazenil in the late LP, a period of progesterone
      withdrawal, compared to the FP. METHODS: Twelve healthy females, without history
      of psychiatric disorder, were randomized to receive two injections of a 2 mg
      bolus injection of flumazenil (one in the late LP and one in the FP) and two
      injections of placebo (one in the late LP and one in the FP). Following
      injection, subjects were asked to rate the occurrence and intensity of panic
      symptoms on the panic symptom scale (PSS). RESULTS: A main treatment effect was
      detected for the PSS score response after flumazenil injection (P=0.008).
      However, there was no significant treatment-by-phase interaction observed
      (P=0.449). CONCLUSIONS: These findings indicate that MC phase did not affect the
      response to flumazenil in HC females. This result is contrary to our hypothesis
      of altered sensitivity to flumazenil in the late LP.

PMID- 14712335
TI  - Effect of the endogenous kappa opioid agonist dynorphin A(1-17) on cocaine-evoked
      increases in striatal dopamine levels and cocaine-induced place preference in
      C57BL/6J mice.
AB  - RATIONALE: Effects of synthetic kappa opioid receptor agonists on cocaine-induced
      reward have been studied extensively in rats but relatively few studies have used
      the endogenous kappa agonist dynorphin A(1-17). OBJECTIVES: Three studies were
      conducted to examine the effect of the natural sequence dynorphin on cocaine
      induced increases in dopamine, on the formation of conditioned place preference
      and on increases in locomotor activity in C57BL/6 J mice. METHODS: After
      implantation of guide cannulae into the caudate putamen, mice were allowed 4-5
      days to recover from surgery. In the first study, dynorphin A (0, 1, 2, 4.4 nmol)
      was infused into the caudate putamen and dopamine levels were measured by in vivo
      microdialysis in that brain region. Then, the effect of dynorphin A (4.4 nmol) on
      increases in dopamine levels induced by 15 mg/kg cocaine i.p. was also measured
      with in vivo microdialysis. The third experiment examined the effect of dynorphin
      A (4.4 nmol) on conditioned place preference and locomotion induced by 15 mg/kg
      cocaine. RESULTS: Dynorphin A significantly decreased basal dopamine levels in a
      dose-dependent manner by more than 60% at the highest dose, and this effect was
      completely blocked by pre-injection of the kappa-opioid receptor antagonist nor
      BNI (10 mg/kg). The highest dose of dynorphin (4.4 nmol) blocked increases in
      dopamine levels, the formation of conditioned place preference and attenuated
      locomotion induced by 15 mg/kg cocaine. CONCLUSION: The blockade of the cocaine
      induced rise in striatal dopamine may contribute to both dynorphin's ability to
      prevent the development of cocaine-induced conditioned place preference and to
      attenuate the increase in locomotor activity.

PMID- 14712337
TI  - Effects of periadolescent versus adult cocaine exposure on cocaine conditioned
      place preference and motor sensitization in mice.
AB  - RATIONALE: Age of initial exposure to addictive substances is inversely
      proportional to risk of developing drug dependence. There is debate, however, as
      to whether intake at a young age causes dependency or whether young people who
      experiment with addictive substances are predisposed to dependency by other
      factors. OBJECTIVES. We tested the relationship between cocaine exposure at two
      different ages in mice and the development of subsequent drug-seeking behavior to
      test for age-specific exposure effects. METHODS: We performed dose-response
      analysis of cocaine conditioned place preference (CPP) and locomotor activity in
      periadolescent and adult C57Bl/6J mice. In addition, we pretreated periadolescent
      and adult C57Bl/6J mice with cocaine or saline in the home cage or a drug
      associated context, and then examined their behavior in a biased CPP procedure in
      adulthood. RESULTS: Dose-response relationships were similar between the two age
      groups. In the pretreatment experiments, we observed locomotor sensitization
      during the pretreatment in periadolescent but not adult mice. We also observed an
      enhanced aversion to the non-preferred side of the chamber in periadolescent mice
      compared to adult mice, which was alleviated by cocaine association with that
      side. Third, we observed that after further conditioning in adulthood, there were
      no pretreatment-specific effects. CONCLUSIONS: Our results are consistent with a
      "vulnerable brain" hypothesis for responses to cocaine based on our findings that
      periadolescent mice exhibit greater locomotor sensitization to cocaine, and
      greater baseline anxiety responses that are alleviated by cocaine exposure
      compared to adult mice.

PMID- 14712336
TI  - Prolonged nicotine dependence associated with extended access to nicotine self
      administration in rats.
AB  - RATIONALE: Most nicotine self-administration (NSA) studies in rats are performed
      under limited-access conditions. Few studies have examined the relationship
      between nicotine dependence and NSA. OBJECTIVES: To determine how NSA access
      conditions affect NSA and the duration of nicotine dependence during abstinence,
      as reflected in somatic signs of withdrawal precipitated by administration of the
      nicotinic receptor antagonist mecamylamine. METHODS: The effects of different NSA
      access conditions (zero, 1 h/5 days, 1 h/7 days and 6 h/7 days per week) and non
      contingent nicotine administration on NSA and somatic signs were examined.
      RESULTS: Daily NSA access (30 days) resulted in spontaneous and mecamylamine
      induced somatic signs. Both daily access groups (1 h/day and 6 h/day, 7
      days/week) exhibited spontaneous somatic signs on day 25 of NSA (17 h post-NSA)
      and sensitivity to mecamylamine up to 2 and 4 weeks of abstinence, respectively.
      In contrast, the 1 h/day, 5 days/week access group exhibited mecamylamine-induced
      somatic signs only up to 1 week of abstinence. NSA behavior was stable in rats
      with 1 h/day 5 days/week and 1 h/day 7 days/week access, but decreased from
      initially high rates in the 6 h/day 7 days/week access group, and decreased in
      rats receiving non-contingent nicotine. In contrast, extended cocaine self
      administration access resulted in a gradual escalation in cocaine intake.
      CONCLUSION: There was no escalation in nicotine intake with extended access
      conditions, unlike cocaine self-administration. Nevertheless, daily nicotine self
      administration seven days per week, for either 1 or 6 h per day, was sufficient
      to induce long-lasting adaptations in nicotinic acetylcholine receptor activity
      reflected in spontaneous and antagonist-precipitated somatic signs of withdrawal,
      possibly reflecting aspects of nicotine dependence.

PMID- 14712338
TI  - 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter
      binding sites in basal ganglia in vivo in schizophrenia.
AB  - RATIONALE: The dopamine hypothesis for schizophrenia postulates overactivity of
      dopamine transmission in the basal ganglia. Most effective antipsychotic drugs
      block postsynaptic dopamine receptors, but in-vivo imaging studies have not been
      able to show changes in these receptors in drug-naive schizophrenics. OBJECTIVES:
      The presynaptic dopamine transporter (DAT) is thought to be an important
      regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta
      CIT, which has a high affinity for DAT, in order to further examine the dopamine
      hypothesis for schizophrenia. METHODS: Six patients with chronic schizophrenia
      treated with classic dopamine D(2)-receptor blocking neuroleptics were
      investigated. The number of DAT binding sites in the basal ganglia was calculated
      and compared with five healthy volunteers and ten parkinsonian patients. RESULTS:
      The schizophrenic patients showed a 36-63% increase in DAT binding sites compared
      with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease.
      The differences between the groups were highly significant (even after correction
      for different age composition within the groups). CONCLUSIONS: There was an
      increased number of DAT binding sites in the schizophrenic patients treated with
      dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent
      reports that have shown increased volumes of basal ganglia in this patient
      category. It thus appears that there is an increased number of presynaptic
      dopamine releasing nerve terminals in the basal ganglia, possibly as a biological
      adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.

PMID- 14712339
TI  - Effects of ayahuasca on binocular rivalry with dichoptic stimulus alternation.
AB  - RATIONALE: During binocular rivalry, two incompatible images are presented to
      each eye and these monocular stimuli compete for perceptual dominance, with one
      pattern temporarily suppressed from awareness. One variant of stimulus
      presentation in binocular rivalry experiments is dichoptic stimulus alternation
      (DSA), when stimuli are applied to the eyes in rapid reversals. There is
      preliminary report that in contrast with healthy controls, schizophrenic patients
      can maintain binocular rivalry even at very high DSA rates. OBJECTIVE: The study
      was undertaken to investigate whether binocular rivalry survives high rates of
      DSA induced by the South American hallucinogenic beverage ayahuasca. METHODS: Ten
      individuals who were participating in ayahuasca ceremonials were requested to
      volunteer for binocular rivalry tests (DSA=0, 3.75, 7.5, 15 and 30 Hz) without
      and after drinking the brew. RESULTS: Ingestion of ayahuasca increased mean
      dominance periods both in standard binocular rivalry conditions (no DSA) and
      tests with DSA. At higher DSA rates (15 and 30 Hz) the total length of dominance
      periods was longer on the brew. CONCLUSION: It is discussed that ayahuasca
      induced survival of binocular rivalry at high DSA rates may be related to slow
      visual processing and increased mean dominance periods may result from
      hallucinogen-induced alteration of gamma oscillations in the visual pathways.

PMID- 14712340
TI  - Effects on cocaine and food self-administration of (+)-HA-966, a partial agonist
      at the glycine/NMDA modulatory site, in rats.
AB  - RATIONALE: (+)-HA-966, a partial agonist at the glycine/NMDA modulatory site,
      significantly reduced i.v. cocaine self-administration in a fixed-ratio (FR)
      schedule. Since this effect was observed studying only one dose of cocaine and
      considering the characteristic bell-shaped curve generated by cocaine in self
      administration studies under FR schedules, the precise nature of the effect is
      not clear. OBJECTIVE: To identify the nature of the effect of (+)-HA-966 on
      cocaine self-administration under fixed ratio (FR) and progressive ratio (PR)
      schedules of reinforcement. METHODS: Rats were prepared with i.v. catheters and
      trained to self-administer cocaine. In the first experiment three doses of (+)-HA
      966 (10, 30 and 100 microg/5 microl i.c.v.) were evaluated for their effects on
      0.25 mg/0.1 ml per infusion cocaine self-administration on FR1 with 20-s time-out
      (TO). Next, 30 microg/5 microl i.c.v. (+)-HA-966 was evaluated as pretreatment on
      a complete dose-response for cocaine self-administration. In a third experiment
      the effect of the same dose was evaluated on cocaine or food self-administered on
      the PR schedule. RESULTS: (+)-HA-966 at doses of 10 or 30 microg reduced cocaine
      self-administration in an FR1 schedule during the first hour interval of the 2-h
      session. This partial agonist at the glycine/NMDA modulatory site also reduced
      the number of injections of cocaine earned during the first hour of the session
      but not the final ratio reached under a PR schedule. However, under this schedule
      (+)-HA-966 also reduced operant responding for food reinforcement. CONCLUSIONS:
      (+)-HA-966 reduced responding maintained by cocaine or food. Whether (+)-HA-966
      induces a general motivational rather than a performance deficit, leading to
      reduced responding for either cocaine and food, is unclear.

PMID- 14712341
TI  - Effects of positive allosteric modulators of the GABAB receptor on cocaine self
      administration in rats.
AB  - RATIONALE: Previous studies have strongly implicated a role for GABA(B) receptors
      in modulating the reinforcing effects of cocaine. OBJECTIVE: The purpose of the
      present study was to examine the efficacy of two novel positive allosteric
      modulators of the GABA(B) receptor, CGP7930 and GS39783, to decrease cocaine self
      administration in rats responding under various schedules of reinforcement.
      METHODS: Rats were trained to self-administer cocaine under progressive ratio
      (PR), fixed ratio (FR) and discrete trials (DT) schedules of reinforcement, and
      the ability of CGP7930 and GS39783 to decrease cocaine-maintained responding was
      examined. RESULTS: On a PR schedule, CGP7930 markedly decreased break points
      maintained by 1.5 mg/kg per injection cocaine in a dose-dependent manner. GS39783
      produced only modest decreases in cocaine-reinforced break points, with only the
      highest dose decreasing break points relative to baseline. On an FR1 schedule of
      reinforcement, both drugs decreased responding for a threshold dose of cocaine,
      but did not alter responding for higher doses of cocaine. In a DT procedure, 1.5
      mg/kg per injection cocaine was made available during three 10-min trials each
      hour during 24-h sessions (DT3), engendering a circadian pattern of responding
      characterized by high numbers of infusions during the dark phase and low numbers
      of infusions during the light phase. Doses of 30 mg/kg CGP7930, 3.0 mg/kg GS39783
      and 2.5 mg/kg baclofen significantly decreased cocaine-maintained responding when
      administered at the beginning of the dark phase of the cycle. Across all
      schedules, CGP7930 was more effective at decreasing cocaine self-administration
      than GS39783, a finding that may be due to differences in bioavailability between
      the two drugs. CONCLUSIONS: These findings suggest that positive allosteric
      modulators of the GABA(B) receptor may hold promise as potential
      pharmacotherapies for cocaine abuse and dependence.

PMID- 14712342
TI  - Effect of the kappa opioid agonist R-84760 on cocaine-induced increases in
      striatal dopamine levels and cocaine-induced place preference in C57BL/6J mice.
AB  - RATIONALE: While the effects of several kappa opioid receptor agonists on cocaine
      induced reward have been studied, such effects of R-84760, a novel non-peptidic,
      potent and selective kappa opioid agonist that has been studied in humans, are
      not yet known. OBJECTIVE: To study the effects of R-84760 on basal levels of
      dopamine, cocaine-induced increases in dopamine levels, cocaine-induced
      conditioned place preference and locomotor activity in mice. METHODS: In the
      first experiment, R-84760 was administered i.p. (0, 0.01, 0.05 or 0.1 mg/kg) to
      C57BL/6J mice. Its effect on basal dopamine levels in the caudate putamen was
      measured with in vivo microdialysis. In the second experiment, the effect of
      pretreatment with 0.1 mg/kg R-84760 on cocaine-induced increases in dopamine
      levels was studied. The third experiment examined the effect of R-84760 (0.1
      mg/kg) on the development of cocaine-induced conditioned place preference and
      locomotor activity in the conditioning chamber. RESULTS: R-84760 decreased
      dopamine levels in a dose-dependent manner. The highest dose of R-84760 (0.1
      mg/kg, i.p.) significantly decreased dopamine levels relative to vehicle, an
      effect completely blocked by pre-injection with 10 mg/kg of the kappa-opioid
      receptor antagonist nor-binaltorphimine (nor-BNI). The same dose of R-84760
      blocked cocaine-induced increases in dopamine levels, cocaine-induced conditioned
      place preference and attenuated cocaine-induced locomotor response. CONCLUSION:
      These findings suggest that R-84760 decreases dopamine levels in the caudate
      putamen through kappa-opioid receptors. The inhibitory effect of R-84760 on
      striatal dopamine may contribute to its blockade of cocaine-induced increases in
      dopamine levels, cocaine-induced conditioned place preference and the associated
      increases in locomotor activity.

PMID- 14712343
TI  - Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P
      glycoprotein deficiency in the blood-brain barrier of Abcb1a gene knockout mice.
AB  - RATIONALE: Methadone maintenance treatment is complicated by the wide variability
      of efficacy among patients. The large interindividual variability of the plasma
      concentrations of methadone was previously thought to be responsible for the
      variable therapeutic efficacy. However, recent studies suggested that methadone
      may be a substrate of P-glycoprotein (P-gp). Therefore, the function of P-gp in
      blood-brain barrier (BBB) may affect the concentration of methadone at its
      site(s) of action in the central nervous system, thereby contributing to its
      therapeutic efficacy and/or adverse events. OBJECTIVE: To investigate the effect
      of P-gp on brain penetration of methadone (R)- and (S)-enantiomers and their
      major oxidative metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
      (EDDP). METHODS: We compared the tissue distribution of methadone (R)- and (S)
      enantiomers and EDDP in the Abcb1a-/- gene knockout mice and the Abcb1a+/+ wild
      type mice 1 h following intraperitoneal administration of 15 microg Rac
      methadone/g mouse. RESULTS: Plasma concentrations of (R)- and (S)-methadone were
      similar between the two animal groups. However, the brain concentrations of (R)-
      and (S)-methadone in the Abcb1a-/- mice were markedly higher (15- and 23-fold,
      respectively, P<0.0001) than those of the Abcb1a+/+ wild-type mice. No
      statistically significant difference was found for other organs between the
      mutants and controls. No organ difference was found for EDDP between the mutants
      and controls. CONCLUSIONS: (R)- and (S)-methadone are substrates of P-gp. The P
      gp in BBB greatly limits the brain entry of (R)- and (S)-methadone to their
      central nervous system acting sites. The interindividual variation in expression
      of P-gp in BBB may represent a source of variation for the access and effects of
      methadone in the brain.

PMID- 14712345
TI  - Repair of type-2 SLAP lesions using Corkscrew anchors. A preliminary report of
      the clinical results.
AB  - The aim of the study was to perform a clinical assessment of patients who had
      undergone arthroscopic repair of a type-2 SLAP lesion using one double-looped
      Corkscrew anchor. Fifteen consecutive patients who agreed to fill in a pre- and
      post-operative questionnaire were included in the study. The aetiology was
      traumatic in 10/15 patients and non-traumatic in 5/15. At the index operation
      four patients underwent a concomitant acromioplasty, while four patients
      underwent supplementary anterior labrum fixation using suture anchors.
      Thirteen/15 (87%) of the patients were physically re-examined by independent
      observers after a follow-up period of 25 months (11-32). The questionnaire
      involved a patient-administered assessment of ten common activities of daily
      living. At follow-up, the Rowe score was 84 points (51-98) and the Constant score
      was 83 points (35-100). The external rotation in abduction was 85 degrees (60
      110) on the operated side and 90 degrees (80-110) on the non-operated side (
      p<0.05). The isometric strength in abduction was 8.3 kg (0.8-14.4) on the
      operated side and 8.9 kg (2.7-15.5) on the non-operated side ( p=0.006).
      Significant improvements ( p<0.05) compared with the pre-operative assessments
      were found in 2/10 activities of daily living. Another 4/10 activities seemed to
      improve but did not reach statistical significance ( p<0.08). Eleven of 15
      patients returned to their pre-injury activity level. In conclusion, the majority
      of patients returned to their pre-injury activity level and the subjective
      patient-administered evaluations appeared to improve after arthroscopic repair of
      type-2 SLAP lesions using one double-looped Corkscrew anchor. We feel encouraged
      to continue using this technique.

PMID- 14712346
TI  - Influence of different volume replacement strategies on inflammation and
      endothelial activation in the elderly undergoing major abdominal surgery.
AB  - OBJECTIVE: Adequate restoration of intravascular volume remains an important
      maneuver in the management of the surgical patient. Influence of different volume
      replacement regimens on inflammation/endothelial activation in elderly surgical
      patients was assessed. DESIGN: Prospective, randomized study. SETTING: Surgical
      intensive care unit of a university-affiliated hospital. PATIENTS: Sixty-six
      patients >65 years undergoing major abdominal surgery. INTERVENTIONS: Ringer's
      lactate (RL; n=22), normal saline solution (NS; n=22) or a low-molecular HES
      (mean molecular weight 130 kD) with a low degree of substitution (0.4; HES
      130/0.4; n=22) were administered after induction of anesthesia until the 1st
      postoperative day (POD) to keep central venous pressure between 8-12 mmHg.
      MEASUREMENTS AND RESULTS: C-reactive protein, interleukins (IL-6, IL-8), adhesion
      molecules [endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular
      adhesion molecule-1 (ICAM-1)] were measured prior to volume therapy at the end of
      surgery, 5 h after surgery and at the morning of the 1st POD. RL patients
      received 10,150+/-1,660 ml of RL, NS patients 10,220+/-1,770 ml of NS and the HES
      treated group 2,850+/-300 ml of HES 130/0.4 and 2,810+/-350 ml of RL.
      Hemodynamics were similar in all groups. CRP, IL-6 and IL-8 plasma levels
      increased significantly higher in both crystalloid groups (IL-6 in the NS group:
      increase to 407+/-33 pg/ml; RL: increase to 377+/-35 pg/dl) than in the HES-130
      treated group (IL-6: increase to 197+/-20 pg/dl). Plasma levels of ELAM-1 and
      ICAM remained almost unchanged in the HES 130-, but significantly increased in
      the RL- and NS-treated patients. CONCLUSIONS: In elderly patients, markers of
      inflammation and endothelial injury and activation were significantly higher
      after crystalloid- than after HES 130/0.4-based volume replacement regimens.

PMID- 14712347
TI  - Changes in cardiac repolarization during clinical episodes of nocturnal
      hypoglycaemia in adults with Type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Experimental hypoglycaemia leads to abnormal cardiac
      repolarization manifest by a lengthened QT interval and caused by adrenergic
      stimulation. However it is less clear whether spontaneous clinical episodes lead
      to similar changes. We have therefore measured cardiac ventricular repolarization
      and counterregulatory responses in patients with Type 1 diabetes during
      hypoglycaemic and euglycaemic nights. METHODS: We studied 22 patients with Type 1
      diabetes (mean age 40.4+/-17.2 years, duration of diabetes 17.2+/-9.3 years,
      HbA1c 8.2+/-1.2% overnight). Measurements were taken hourly of blood glucose,
      plasma potassium, catecholamines and high resolution electrocardiograms. RESULTS:
      Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights.
      During overnight hypoglycaemia, QTc interval increased by 27 ms (+/-15) above
      baseline, compared with 9 ms (+/-19) during nights with no nocturnal
      hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (+/
      0.21) above baseline during hypoglycaemia, compared with -0.05 nmol/l (+/-0.08)
      during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant
      difference between potassium, and noradrenaline concentrations between the two
      groups. CONCLUSION/INTERPRETATION: QTc interval lengthens significantly during
      spontaneous nocturnal hypoglycaemia. Increases are generally less than those
      observed during experimental hypoglycaemia and could reflect attenuated
      sympathoadrenal responses during clinical episodes. The clinical relevance of
      these changes is uncertain but is consistent with the hypothesis that clinical
      hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of
      cardiac arrhythmia.

PMID- 14712348
TI  - Prolonged increase of plasma non-esterified fatty acids fully abolishes the
      stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity
      and pancreatic beta-cell function in obese men.
AB  - AIMS/HYPOTHESIS: A prolonged increase of plasma NEFA impairs acute glucose
      stimulated insulin secretion (GSIS) in vitro and in vivo. Our study therefore
      examined the combined effect of increased plasma NEFA and glucose on GSIS in
      humans. METHODS: We examined GSIS on four occasions in eight obese men during a
      10 mmol/l hyperglycaemic clamp and after a 24-h infusion of (i) normal saline,
      (ii) intralipid and heparin to raise plasma NEFA about two-fold above basal,
      (iii) 20% dextrose to raise plasma glucose to about 7.5 mmol/l and (iv)
      intralipid and heparin combined with 20% dextrose to raise plasma NEFA and
      glucose. RESULTS: In study (iii) insulin sensitivity was about 20% greater than
      in study (i) and the disposition index was about 50% higher. Insulin sensitivity
      tended to be lower in study (ii) whereas the disposition index was lower than in
      study (i), confirming previous observations. The combination of increased plasma
      NEFA and glucose (study iv) reduced insulin sensitivity in comparison with study
      (i) and completely abolished the increase in insulin sensitivity and disposition
      index seen in study (iii), but did not reduce the latter to a lower value than
      that in the saline control study (study i). CONCLUSIONS/INTERPRETATION: We showed
      that a prolonged increase of plasma NEFA completely abolishes the stimulatory
      effect of moderate hyperglycaemia on insulin sensitivity and beta-cell function
      in obese humans. This suggests that previous observations, showing that a
      prolonged increase of plasma NEFA impairs pancreatic beta-cell function, also
      apply to the hyperglycaemic state.

PMID- 14712349
TI  - Dietary iron intake and Type 2 diabetes incidence in postmenopausal women: the
      Iowa Women's Health Study.
AB  - AIMS/HYPOTHESIS: Recently, a clear biological link between iron metabolism and
      diabetes has emerged from epidemiological and experimental studies. We carried
      out a prospective study of dietary iron intake and incidence of Type 2 diabetes.
      METHODS: 35,698 postmenopausal women initially aged 55 to 69 years were followed
      for 11 years. Diet was assessed with a food frequency questionnaire at baseline.
      RESULTS: Intake of heme iron showed a positive association with incident Type 2
      diabetes; the relative risks were 1.0, 1.07, 1.12, 1.14, and 1.28 across
      quintiles of heme iron (p trend =0.02) after adjustment for non-dietary and
      dietary risk factors. Heme iron showed a weak positive association among non
      drinkers, but the association appeared to be stronger among subjects who consumed
      more alcohol. For example, in a model restricted to those who drank alcohol at
      least 15 g/day, adjusted relative risks across quintiles of heme iron were 1.0,
      2.26, 3.22, 1.92, and 4.42 (p trend =0.05); and consumers of 30 g/day of more of
      supplemental iron had an adjusted relative risk equal to 3.03 (95% CI, 1.29
      7.12)], compared to those who took no iron supplement. Non-heme iron was
      inversely associated with incidence of Type 2 diabetes. Amongst non-drinkers
      adjusted relative risks were 1.0, 0.83, 0.87, 0.72, and 0.67 across quintiles (p
      trend <0.01). This inverse association was lost among drinkers, in whom there was
      no association of diabetes incidence with non-heme iron.
      CONCLUSIONS/INTERPRETATION: Greater dietary heme-iron intake and/or supplemental
      iron were associated with an increased risk of Type 2 diabetes, especially
      amongst those who drink alcohol.

PMID- 14712350
TI  - Retinoic acid receptor alpha and retinoid X receptor specific agonists reduce
      renal injury in established chronic glomerulonephritis of the rat.
AB  - Retinoids, derivatives of vitamin A, inhibit mesangial cell proliferation,
      glomerular inflammation, and extracellular matrix deposition in acute anti-Thy1.1
      glomerulonephritis (Thy-GN) of the rat. We examined a model, chronic
      mesangioproliferative Thy-GN (MoAb 1-22-3), which is more akin to human disease.
      Treatment started on day 23 when Thy-GN had already been established.
      Nonnephritic control and Thy-GN rats were treated orally for 67 days with vehicle
      or with two doses of either the retinoic acid receptor alpha-specific agonist AGN
      195183 (RARalpha agonist) or the retinoid X receptor specific agonist AGN 194204
      (RXR agonist). Doses of either the RARalpha or the RXR agonist significantly
      reduced albuminuria and normalized blood pressure during the course of treatment.
      The glomerulosclerosis index, glomerular cell and interstitial cell counts, and
      area of the interstitial space were significantly lower in nephritic rats treated
      with the RARalpha agonist or RXR agonist than with vehicle. The RARalpha and RXR
      agonist significantly reduced the infiltration of the glomerulus by macrophages.
      The increase in glomerular TGFbeta1 and prepro-ET(1) gene expression in vehicle
      treated nephritic rats was significantly attenuated by RARalpha or RXR agonists.
      Glomerular expression of RXRalpha and RARalpha receptor mRNA was significantly
      greater in vehicle-treated nephritic rats than in nonnephritic controls.
      Treatment with RARalpha or RXR agonists tended to normalize retinoid-receptor
      gene expression. Our data indicate that both RARalpha agonists and RXR agonists
      reduce renal damage in rats with established chronic glomerulonephritis. Receptor
      specific retinoids may provide a novel therapeutic approach for the treatment of
      chronic glomerulonephritis.

PMID- 14712352
TI  - From gene function to improved health: genome research in the United Kingdom.
AB  - The United Kingdom has a prestigious track record in genetic and genomic
      research, with the structure of DNA, and delivery of a third of the human genome
      being significant landmarks. UK genomic research benefits from a variety of
      funding sources in both the public and private sector, and efforts to co-ordinate
      research strategies. Here we describe how this investment has impacted on the UK
      research capacity and highlight examples of progress in translating genetic
      information into improved healthcare.

PMID- 14712353
TI  - The role of podocytes in glomerular pathobiology.
AB  - Podocytes are unique cells with a complex cellular organization. With respect to
      their cytoarchitecture, podocytes may be divided into three structurally and
      functionally different segments: cell body, major processes, and foot processes
      (FPs). The FPs of neighboring podocytes regularly interdigitate, leaving between
      them the filtration slits that are bridged by an extracellular structure, known
      as the slit diaphragm (SD). Podocytes cover the outer aspect of the glomerular
      basement membrane (GBM). They therefore form the final barrier to protein loss,
      which explains why podocyte injury is typically associated with marked
      proteinuria. Chronic podocyte injury may lead to podocyte detachment from the
      GBM. Our knowledge of the molecular structure of the SD has been remarkably
      improved in the past few years. Several molecules, including nephrin, CD2AP, FAT,
      ZO-1, P-cadherin, Podocin, and Neph 1-3 have all been shown to be associated with
      the SD complex, and some of these molecules are critical for its integrity.
      Podocytes are injured in many forms of human and experimental glomerular disease.
      The early events are characterized either by alterations in the molecular
      composition of the SD without visible changes in morphology or, more obviously,
      by a reorganization of FP structure with the fusion of filtration slits and the
      apical displacement of the SD. Based on recent insights into the molecular
      pathology of podocyte injury, at least four major causes have been identified
      that lead to the uniform reaction of FP effacement and proteinuria: (1)
      interference with the SD complex and its lipid rafts; (2) direct interference
      with the actin cytoskeleton; (3) interference with the GBM or with podocyte-GBM
      interaction; and (4) interference with the negative surface charge of podocytes.
      There is also evidence, in focal segmental glomerular sclerosis (FSGS) and in
      idiopathic nephrotic syndrome in humans and rats, that podocyte damage may be
      caused by circulating albuminuric factors. Ongoing studies in many laboratories
      are aiming at an understanding of the dynamic relationship between SD proteins,
      the actin cytoskeleton, and the dynamics of FP structure in nephrotic syndrome
      and FSGS. These studies should provide us with a better understanding of the
      biological mechanism underlying the podocyte response to injury. Such studies
      will potentially translate into more refined treatment and the prevention of
      proteinuria and progressive glomerular disease.

PMID- 14712351
TI  - Linking DJ-1 to neurodegeneration offers novel insights for understanding the
      pathogenesis of Parkinson's disease.
AB  - Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding
      of the molecular pathways involved in the common, non-Mendelian forms of the
      disease. Here, we focus on PARK7, an autosomal recessive form of early-onset
      parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics
      of this form and the rapidly expanding knowledge about the structure and
      biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction
      might lead to neurodegeneration, and the implications of this novel piece of
      information for the pathogenesis of the common PD forms. Although much work
      remains to be done to clarify the biology of DJ-1, its proposed activity as a
      molecular chaperone and/or as oxidative sensor appear intriguing in the light of
      the current theories on the pathogenesis of PD.

PMID- 14712354
TI  - Podocyte cytoskeleton is connected to the integral membrane protein podocalyxin
      through Na+/H+-exchanger regulatory factor 2 and ezrin.
AB  - During development, glomerular visceral epithelial cells, or podocytes, undergo
      extensive morphologic changes necessary for the creation of the glomerular
      filter. These changes include formation of interdigitating foot processes,
      replacement of tight junctions with slit diaphragms, and the concomitant opening
      of filtration slits. It was postulated previously and confirmed recently that
      podocalyxin, a sialomucin, plays a major role in keeping the urinary space open
      by virtue of the physicochemical properties of its highly negatively charged
      ectodomain. By a cell aggregation assay, the expression level of podocalyxin
      correlated closely with the anti-adhesion effect. Treatment of the cells with
      sialidase reversed the inhibitory effect of podocalyxin, indicating that sialic
      acid residue is required for inhibition of cell adhesion. In addition to its
      ectodomain, the highly conserved cytoplasmic tail of podocalyxin may contribute
      to the unique organization of podocytes. By immunocytochemistry, it was shown
      that two cytosolic adaptor proteins, Na(+)/H(+)-exchanger regulatory factor 2
      (NHERF2) and ezrin, colocalize with podocalyxin along the apical plasma membrane
      of podocytes, where they form a co-immunoprecipitable complex. Moreover, the
      podocalyxin/NHERF2 /ezrin complex interacts with the actin cytoskeleton, and this
      interaction is disrupted in pathologic conditions associated with changes in the
      foot processes, indicating its importance in maintaining the unique organization
      of this epithelium. Further studies will be needed to identify the signaling
      molecules responsible for the regulation of this complex in podocyte damage.

PMID- 14712355
TI  - Comparison of antiproteinuric effects of two different combination therapies in
      children with IgA nephropathy.
AB  - BACKGROUND: Because moderate or severe proteinuria is a representative factor
      indicative of longterm poor prognosis in IgA nephrology, an anti-proteinuric
      treatment which can be administered longterm with few side effects is necessary.
      We report here a comparison of antiproteinuric effects in two patient groups
      treated with different combination therapies. METHODS: Group A comprised 12
      patients with IgA nephropathy, who had 24-h proteinuria of 0.5 gm(2) or more,
      moderately severe renal histology, and normal renal function, and were treated
      with a combination of drugs, i.e., prednisolone, an immunosuppressant
      (mizoribine), an anti-platelet drug (dipyridamole), and an angiotensin-converting
      enzyme inhibitor. Group B consisted of 18 patients who had baseline
      characteristics similar to those of the patients in group A and were treated with
      our previous protocol (a combination of prednisolone, cyclophosphamide, and
      dipyridamole). Twenty-four-hour proteinuria and creatinine clearance were
      measured every 6 months. The primary endpoint was reduction of 24-h proteinuria
      by less than 25% compared with the baseline value. RESULTS: The proportion of
      patients that exhibited the primary endpoint, as assessed by the Kaplan-Meier
      method, was found to be significantly higher in group A than in group B (logrank
      test; P = 0.024). None of the patients in the two groups experienced serious
      adverse effects. CONCLUSIONS: The results suggested that the use of drugs in
      combination with cyclophosphamide was beneficial for patients with moderately
      severe IgA nephropathy. Because moderate or severe proteinuria is a
      representative factor indicative of longterm poor prognosis in IgA nephropathy,
      an anti-proteinuric treatment which can be administered longterm with few side
      effects is necessary. We report here a comparison of antiproteinuric effects in
      two patient groups treated with different combination therapies.

PMID- 14712356
TI  - Clinical course of bucillamine-induced nephropathy in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Bucillamine, a disease-modifying antirheumatic drug widely prescribed
      in Japan, is reported to be a cause of proteinuria. However, to date, the
      clinical course of the nephropathy associated with the use of bucillamine has not
      been described in detail. METHODS: We analyzed renal biopsy findings from 10
      patients with rheumatoid arthritis and concomitant bucillamine-induced
      nephropathy. Each patient was followed up until proteinuria had resolved.
      RESULTS: Proteinuria appeared 2-11 months after the initiation of the treatment
      with bucillamine. Nine patients, who stopped bucillamine treatment immediately
      (within 3 months) after the onset of proteinuria, were diagnosed as having stage
      I membranous nephropathy. Only one patient, who used bucillamine for 9.5 months
      after the onset of proteinuria, was diagnosed as having stage II membranous
      nephropathy. In all patients with stage I membranous nephropathy, the proteinuria
      disappeared within 7 months after they stopped bucillamine treatment. On the
      other hand, in the patient with stage II membranous nephropathy, the proteinuria
      persisted for 14 months after the use of bucillamine was stopped. In all the
      patients, the proteinuria resolved completely without deterioration of renal
      function. None of the patients has experienced recurrence of proteinuria.
      CONCLUSIONS: In patients with proteinuria induced by treatment with bucillamine,
      membranous nephropathy is the most common disorder. Immediate withdrawal of
      bucillamine results in prompt and complete resolution of proteinuria without
      deterioration of renal function.Bucillamine, a disease-modifying antirheumatic
      drug widely prescribed in Japan, is reported to be a cause of proteinuria.
      However, to date, the clinical course of the nephropathy associated with the use
      of bucillamine has not been described in detail.

PMID- 14712357
TI  - Infusion of radiocontrast agents induces exaggerated release of urinary
      endothelin in patients with impaired renal function.
AB  - BACKGROUND: The aim of the study was to examine the role of endothelin in
      radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.
      METHODS: We measured plasma endothelin-1 (ET) and the urinary excretion of
      endothelin-like immunoreactivity before and after infusion of radio contrast
      medium (CM) in patients with normal renal function (group N; n = 6; mean serum
      creatinine concentration, 0.8 +/- 0.1 (SEM) mg/dl), and in another group, with
      renal dysfunction (group R; n = 6; 2.7 +/- 0.5 mg/dl). Half-normal saline (0.45%
      NaCl solution) was continuously infused in all patients for 25 h, at a rate of
      100 ml/h; starting from 5 h before the infusion of CM. RESULTS: Plasma ET in
      group R (5.2 +/- 1.4 pg/ml) was significantly higher than in group N (0.9 +/-
      0.3; P << 0.01). Urinary endothelin excretion corrected by creatinine
      concentration (uET/Cr) in group R (7.9 +/- 2.4 mg/g Cr) was significantly higher
      than in group N (1.5 +/- 0.4 mg/g Cr; P << 0.05). Urinary excretion levels of N
      acetyl-Beta- d-glucosaminidase (NAG) and Beta2-microglobulin (Beta2M) were also
      significantly higher in group R (0.8 +/- 0.2 mU/g Cr and 670 +/- 400 mg/g Cr,
      respectively) than in group N (0.3 +/- 0.1 and 7.5 +/- 2.2, respectively). After
      CM infusion, uET/Cr in group R significantly increased, to 10.7 +/- 2.6 mg/g Cr
      on the next day and returned to baseline level on the third day. NAG and Beta2M
      showed a similar pattern, but a significant change in NAG was observed on the
      second day in group R. In group N, uET/Cr, NAG, and Beta2M did not change after
      CM infusion. Plasma ET remained unchanged throughout the observation period of 4
      days in both groups. No patient developed pulmonary edema or a significant rise
      in serum creatinine (more than 0.5 mg/dl), caused by infusion of the amount of
      half-normal saline used. CONCLUSIONS: In the present study, uET/Cr increased
      after the administration of CM only in the patients with renal impairment. This
      difference in endothelin reaction may be a causal one, in that patients with
      renal insufficiency readily develop RCN. The infusion of half-normal saline
      starting before CM infusion causes no side effects and is safe for the prevention
      of CM-induced acute renal failure. The aim of the study was to examine the role
      of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic
      renal failure.

PMID- 14712358
TI  - IgA-associated glomerulonephritis with membranoproliferative glomerulonephritis
      like pattern in two children.
AB  - In this article, we report two patients with IgA-associated glomerulonephritis
      with a membranoproliferative glomerulonephritis (MPGN) -like pattern. Both
      patients had nephrotic syndrome at onset. One patient was treated with high-dose
      alternate-day prednisolone (PSL), and the other with indomethacin and low-dose
      PSL. One lost the urinary abnormalities 3 years after starting treatment. The
      other lost the nephrotic state and hematuria over a 5-year period, but
      proteinuria persisted until the last follow-up. Both patients had diffuse
      proliferative changes with mesangial interposition and subendothelial deposits,
      associated with strongly positive deposits of C3 and IgA along the capillary
      walls of the glomeruli. These two patients showed histological changes compatible
      with type-I MPGN, but the pattern of IgA deposits was not typical of idiopathic
      MPGN or IgA nephropathy. We assume this is a rare form of MPGN, not associated
      with liver disease or other systemic diseases.

PMID- 14712359
TI  - Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis
      with hypocomplementemia and elevated anti-streptolysin O treated with
      prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II
      receptor antagonist.
AB  - A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria,
      hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA),
      and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed
      diffuse mesangial and endocapillary glomerulonephritis with crescent formation
      and duplication of the capillary loop on light microscopic examination. Mild to
      moderate proliferation of mesangial matrix and cells were observed. On
      immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4
      to the mesangium and capillary wall were observed. By electron microscopy (EM),
      mesangial, subendothelial, and subepithelial deposits were recognized. However,
      microtubular structure in glomerular endothelial cells, fingerprint structures,
      and circumferential mesangial interposition were not observed by EM. The patient
      was referred to our hospital, but there was no change in her proteinuria 3 weeks
      after admission. The elevation of ASO, hypocomplementemia, and endocapillary
      proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive
      ANA, the persistent hypocomplementemia, and various deposits detected by IF and
      EM suggested lupus nephritis; however, she did not fulfill the classification
      criteria of systemic lupus erythematosus. We started prednisolone (40 mg/day)
      with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and
      endocapillary proliferative glomerulonephritis, but it was not effective for the
      proteinuria. Quinapril (10 mg/day) and losartan (25 to 50 mg/day) were
      administered and the proteinuria decreased. It is possible that this use of an
      angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist
      was effective in reducing the proteinuria in this patient.

PMID- 14712360
TI  - Fibrillary glomerulonephritis associated with essential thrombocytosis.
AB  - A 68-year-old man with a 30-year history of essential thrombocytosis developed
      nephrotic syndrome. Renal biopsy showed massive deposits of Congo red-negative
      periodic acid Schiff (PAS)-positive substance in the mesangium and capillary wall
      that was positive for IgG. Electron microscopic examination revealed 10- to 20-nm
      fibrils in the deposits, and there was no other organ involvement; thus, we
      diagnosed fibrillary glomerulonephritis. This is the first report of a case of
      fibrillary glomerulonephritis associated with essential thrombocytosis.

PMID- 14712361
TI  - POEMS syndrome caused refractory ascites in a polycystic disease patient
      undergoing hemodialysis.
AB  - A 60-year-old man with polycystic disease (PCD) undergoing hemodialysis was
      admitted to our hospital because of refractory ascites in September 2000. He had
      been diagnosed with probable chronic inflammatory demyelinating polyradiculopathy
      6 months before admission. Though the ascites was bloody and exudative, the
      cytology was normal and cultures of bacteria and acid-fast bacillus were both
      negative. Hepatic venous outflow obstruction was excluded by several radiological
      examinations. Because of the presence of polyneuropathy, organomegaly, endocrine
      abnormality, M-protein, plasma cell dyscrasia, and skin lesions, POEMS, syndrome
      was diagnosed; this had caused the refractory ascites. Initial prednisolone
      therapy was effective for the refractory ascites, but it was not effective in
      preventing recurrence. He died due to cachexia in December 2000. This is a very
      rare case of the presence of both PCD and POEMS syndrome in a patient.

PMID- 14712362
TI  - Deep venous thrombosis, myocardial infarction, and occlusion of vascular access
      associated with heparin-induced thrombocytopenia in a diabetic hemodialysis
      patient.
AB  - We report a patient with diabetic endstage renal disease with an initial platelet
      count of 17.6 x 10(4)/mm3 who developed type-II heparin-induced thrombocytopenia
      (HIT) during the induction period of hemodialysis (HD) when unfractionated
      heparin was used. Because the recognition of the condition and the treatment of
      this patient with HIT was unsatisfactory, she developed deep venous thrombosis,
      myocardial infarction, and occlusion of vascular access, at times of platelet
      counts of 4.1 x 10(4), 7.7 x 10(4), and 6.4 x 10(4)/mm3, respectively, with
      antibodies to heparin/platelet factor 4 complex. Unfortunately, we misjudged in
      our belief that the thromboembolic events might be associated with an underlying
      procoagulant state in diabetic nephrotic syndrome, rather than being associated
      with the clinical picture of HIT. This case report suggests that the clinician
      must consider HIT in the differential diagnosis for thromboembolic complications
      during the induction period of HD, because unfractionated heparin is the major
      anticoagulant used in HD.

PMID- 14712363
TI  - Tranexamic acid-induced visual impairment in a hemodialysis patient.
AB  - We report a case of overdosage of tranexamic acid (TNA), which was suggested as
      the cause of visual impairment in a 56-year-old man. He had been undergoing
      chronic hemodialysis for 1 year, following 10 years of peritoneal dialysis. He
      had been hospitalized for an emergency operation for a bleeding ulcer of the
      stomach and duodenum. After the operation, he experienced a gradual loss of sight
      over about 1 week, although his general condition was good. He received
      intravenous injections of TNA as a hemostat during hospitalization for the
      operation. Two weeks after the operation he became blind. Retinography was flat
      and his visual field had become narrowed. On fluorescein angiography,
      microgranular hyperfluorescence, which indicated malfunction of the pigmented
      layer of the retina, was observed. No abnormality of the brain or the optic nerve
      was shown by magnetic resonance imaging. Concentrations of vitamins and trace
      minerals in the blood were within the normal ranges. Administration of vitamins A
      and B(12) did not improve his sight. However, discontinuation of TNA rapidly
      restored his sight, within a few days. He had received TNA once before because of
      bleeding ulcer, and his sight had been impaired at that time. Based on the
      repeated episodes, it was strongly suggested that an overdose of TNA in this
      dialysis patient caused the sight disturbance. Because TNA is metabolized by the
      kidney, caution is necessary when prescribing TNA for patients with renal
      failure.

PMID- 14712364
TI  - Mixed bacteremia with Capnocytophaga sputigena and Escherichia coli following
      bone marrow transplantation: case report and review.

PMID- 14712365
TI  - Semiquantitative culture of open surgical wounds for diagnosis of surgical site
      infection.
AB  - The aim of this study was to assess the performance of a semiquantitative culture
      method and traditional qualitative culture for the diagnosis of surgical site
      infections resulting in an open wound. Results were correlated with the
      definitions for the diagnosis of SSI proposed by the Centers for Disease Control
      and Prevention, Atlanta, Ga., USA. The sensitivity, specificity, positive and
      negative predictive values of the qualitative culture method were 96%, 61%, 84%
      and 89%, respectively. For the semiquantitative technique with a breakpoint of 15
      colony forming units/plate these values were 91%, 96%, 98% and 83%, respectively.
      Analysis of the receiver operating characteristic curve revealed an area under
      the curve of 94.44% (95% confidence interval, 88.5%-99%) for the semiquantitative
      method. This result indicates that our easy-to-perform semiquantitative culture
      technique for open surgical wounds correlates better with the diagnosis of SSI
      than the traditional qualitative method.

PMID- 14712366
TI  - Measures to prevent healtcare workers from contracting severe acute respiratory
      syndrome during high-risk surgical procedures.

PMID- 14712367
TI  - Dissemination of emm28 erythromycin-, clindamycin- and bacitracin-resistant
      Streptococcus pyogenes in Spain.
AB  - Reported here is an unusual cluster of non-invasive infections caused by an emm28
      Streptococcus pyogenes strain resistant to bacitracin, erythromycin and
      clindamycin detected in Santander, Spain. Since one of the characteristics of
      group A streptococci is their almost uniform susceptibility to bacitracin, this
      finding was unusual, and a search for bacitracin-resistant Streptococcus pyogenes
      strains was conducted in two other distant cities of Spain (Madrid and San
      Sebastian) where their presence was confirmed. These strains were frequently
      associated with erythromycin- and clindamycin-resistance, and most of them
      belonged to a unique emm28 T28, ST52 clone.

PMID- 14712368
TI  - Fatal case of community-acquired pneumonia caused by Legionella longbeachae in a
      patient with systemic lupus erythematosus.
AB  - Reported here is a rare case of atypical pneumonia due to a non- pneumophila
      Legionella sp. that occurred in a young patient with systemic lupus
      erythematosus. In spite of aggressive treatment, the patient died 24 h following
      admission to the intensive care unit. Legionella longbeachae was cultured from
      respiratory tract specimens and identified to the genus level by PCR and to the
      species level by an immunofluorescence test. Since most current laboratory tests
      for Legionella spp., including urinary antigen and serology, cannot detect
      infections caused by non- pneumophila Legionella spp., culture on legionella
      selective media should be strongly considered when diagnosing immunosuppressed
      patients with pneumonia.

PMID- 14712369
TI  - Immunocompetent hosts as a reservoir of pneumocystis organisms: histological and
      rt-PCR data demonstrate active replication.
AB  - The present study was conducted to further examine recent data suggesting that
      pneumocystosis could be transmitted between patients and healthcare workers in
      the hospital environment, as has been proven with Pneumocystis-infected SCID mice
      and immunocompetent Balb/c mice. Using an experimental design (i.e., SCID-Balb/c
      mouse airborne transmission system), the present work found that healthy host-to
      healthy host transmission of Pneumocystis organisms can occur, and that 'second'
      healthy contacts are able to transmit the infectious organisms to
      immunocompromised hosts. Further tests designed to explore the behavior of
      Pneumocystis organisms in the lungs of immunocompetent hosts were performed using
      histological and molecular approaches (e.g. testing the expression of both cyclin
      dependent serine-threonine kinase and heat-shock 70 protein in Pneumocystis). The
      results showed Pneumocystis organisms were able to replicate in the lungs of
      immunocompetent hosts, which indicates these hosts are a reservoir for
      Pneumocystis spp.

PMID- 14712370
TI  - Recurrences after laparoscopic ventral hernia repair: results and critical
      review.
AB  - We describe the whole cohort of patients operated on laparoscopically for ventral
      hernias at our institution. Information on early results, complications, and long
      term follow-up was collected prospectively. Of 90 operations attempted, five
      (5.8%) required conversion. Of the remaining 85 patients, 65 (76%) had an
      incisional hernia, while 20 (24%) had primary defects. Three trocars were
      routinely employed (Hasson and two 5-mm). The prosthetic mesh used was ePTFE
      inserted through the first trocar and fixed using helicoidal staplers. Patients
      were periodically followed in the outpatient clinic for at least 12 months
      postoperatively and contacted at the time of this review. Mean operative time was
      101 min. We had three small bowel injuries repaired laparoscopically.
      Postoperative pain was limited. Bowel movements, deambulation, and discharge were
      prompt. We had six (7%) urinary retentions, eight (9%) seromas, three (3.5%)
      cases of pneumonia, two (2%) cases of postoperative vomiting, and one (1%)
      prolonged ileus, which resolved spontaneously on postoperative day 2. Mean
      postoperative stay was 4 days. One patient was readmitted after 4 weeks with
      incomplete obstruction, resolved conservatively. There were three recurrences
      (3.5%), which developed within 1 year of the operation, and a trocar-site
      herniation (1%). The technique appears safe and efficacious.

PMID- 14712373
TI  - Periaortitis: gadolinium-enhanced magnetic resonance imaging and response to
      therapy in four patients.
AB  - The objective of this study was to define clinical and imaging characteristics of
      periaortitis prior to and after therapy with immunosuppressive drugs. Four
      consecutive patients with periaortitis (two secondary to atherosclerosis and two
      with rheumatic diseases) were studied with contrast-enhanced CT and magnetic
      resonance angiography (MRA), rheumatologic serologies, and acute-phase reactants.
      All were treated with corticosteroids and two patients received immunosuppressive
      agents. Patients were followed with serial MRA scans, CT scans, and clinical
      exams. Prior to treatment, all patients demonstrated a rind of periaortic tissue,
      which was enhanced with both contrast-enhanced CT as well as gadolinium-enhanced
      MRA. Clinical symptoms resolved and rind contracture occurred in all cases
      following therapy. Enhancement of the rind persisted despite the clinical
      improvement in all patients. No patient developed an aortic aneurysm or
      retroperitoneal fibrosis during the follow-up period.
      Corticosteroid/immunosuppressive treatment was continued for an average of 41
      months. At 62 months of total follow-up, there has been no recurrence of
      periaortitis by clinical and/or radiologic exam. Treatment of periaortitis with
      corticosteroids and immunosuppression therapy leads to resolution of clinical
      symptoms and radiologic contracture of the periaortic rind. Patients responded to
      therapy without developing progressive fibrosis or aneurysm. MRA allows safe and
      repetitive imaging of periaortitis and provides excellent definition of lumenal
      abnormalities including plaque rupture.

PMID- 14712377
TI  - Late-onset type II endoleaks and the incidence of secondary intervention.
AB  - Type II endoleaks are a recognized complication of endoluminal treatment of
      abdominal aortic aneurysms. In order to better understand the natural history of
      type II endoleaks and their influence on secondary procedures, we examined our
      experience with patients who developed isolated type II endoleaks 6 months or
      more after their original procedure. We conducted a retrospective review of
      patients who underwent endoluminal repair of infrarenal abdominal aortic
      aneurysms with bifurcated endoluminal devices at a single institution from June
      1996 to June 2000. Endoleak surveillance was performed on all patients by using a
      defined CT angiogram protocol. Patients with definitive and isolated type II
      endoleaks on CT angiogram were identified. Patients with indeterminate endoleaks
      or a combination of different types of endoleaks were excluded. Data were
      analyzed on the basis of early (<6 months) or late occurrence of isolated type II
      endoleak. Fifty patients were identified with isolated type II endoleaks. Of
      these patients, 20 (40%) had endoleaks discovered before the 6-month follow-up
      interval whereas the majority (60%) had new type II leaks discovered at least 6
      months after their initial procedure. The timing of endoleak occurrence did not
      significantly influence the rate of spontaneous endoleak resolution between the
      early- (<6 months) and late-onset (>6 months) groups, which was nearly identical
      (40% vs. 43%). Ten patients in the early group and seven of the late-onset group
      required secondary intervention for treatment of type II endoleak (50% vs. 23%;
      NS). Three patients in the early group underwent surgical conversion (vs. 0
      patients in the late-onset group). The mortality rate was not significantly
      different between groups (15% vs. 7%). Most isolated type II endoleaks in this
      patient population occurred 6 months or more after initial endoluminal repair of
      infrarenal abdominal aortic aneurysm. Timing of type II endoleak occurrence did
      not significantly affect the rates of spontaneous resolution or mortality.
      Although differences were observed in the number of patients receiving secondary
      interventions, these findings did not reach statistical difference. All patients
      who required surgical conversion had early type II endoleaks. There were no
      observed ruptures in patients with increased aneurysm size treated with secondary
      intervention or those with stable aneurysm volumes who were followed without
      intervention. The continued development of type II endoleaks beyond the
      perioperative period supports the need for continued endoleak surveillance.

PMID- 14712378
TI  - Spontaneous infrarenal abdominal aortic dissection presenting as claudication:
      case report and review of the literature.
AB  - Spontaneous infrarenal abdominal aortic dissection (SIAAD) is rare. Patients with
      SIAAD may be asymptomatic or may present with abdominal pain or lower extremity
      ischemia. We describe a case report of a patient with SIAAD who presented with
      claudication. We reviewed the English literature on this disorder and
      specifically evaluated the differences between patients on the basis of their
      presenting symptoms. Patients who had SIAAD and lower extremity ischemia were
      more likely to have the dissection process extend into the iliac or femoral
      artery and were less likely to have an associated abdominal aortic aneurysm.
      Aortic rupture in the presence of SIAAD was associated with increased risk of
      death.

PMID- 14712379
TI  - Hemodynamic changes occurring during the progressive enlargement of abdominal
      aortic aneurysms.
AB  - The purpose of this study is to characterize the evolution of the hemodynamic
      forces acting on the arterial walls at progressive stages of enlargement of
      abdominal aortic aneurysms (AAA). The specific aims are twofold: first, to
      determine the magnitude of the "wall shear stresses" (WSS) and their spatial and
      temporal gradients at various stages of enlargement, and second, to identify the
      critical size at which the formation of regions of stasis and/or the transition
      to a turbulent state occur inside the AAA. A parametric in vitro study of the
      pulsatile blood flow was conducted in rigid models of AAA by systematically
      varying the hemodynamic conditions and the size of the aneurysm. The
      instantaneous flow characteristics inside the AAA models were measured along the
      cardiac cycle, using tomographic digital particle image velocimetry (TDPIV). The
      TDPIV measurements showed that even for the case of large dilatation ratios
      (internal diameter >4.5 mm), the flow inside the AAA remained fully attached to
      the walls during systole, but massively detached during diastole. A critical
      aneurysm aspect ratio (length-to-diameter ratio) was found, for which a
      transition to a turbulent state occurred. The formation of internal shear layers
      (internal jet) and slowly recirculating regions (stasis) generated large spatial
      gradients of WSS and regions of low and oscillating WSS. The formation of regions
      of flow stasis was observed even at very early stages in the aneurysm
      enlargement. These spatial and temporal variations in the hemodynamic forces, the
      formation of regions of stasis, and the transition to turbulence are postulated
      to play an important role in the etiology of the disease by activating
      endoluminar thrombus formation, lipid deposition, and certain inflammatory
      mechanisms.

PMID- 14712380
TI  - Ischemic colitis following translumbar thrombin injection for treatment of
      endoleak.
AB  - Endoleaks remain a significant challenge after endovascular abdominal aortic
      aneurysm repair (EVAR). Translumbar thrombin injection of the aneurysm sac has
      been used to treat endoleaks, with low reported morbidity. We present an unusual
      case of ischemic colitis following translumbar thrombin injection of an endoleak.
      A 67-year-old male with a 5.8-cm abdominal aortic aneurysm (AAA) was evaluated
      for endograft repair. The patient underwent preoperative embolization of the
      right hypogastric artery. The AAA was repaired using a unibody bifurcated graft
      (Ancure). Completion aortogram revealed no endoleak and a widely patent left
      hypogastric artery. Computed tomography (CT) at 2 months showed an endoleak
      appearing to originate from a lumbar artery near the proximal attachment site
      with outflow via the inferior mesenteric artery (IMA). The endoleak was
      successfully treated with CT-guided translumbar injection of 8000 units of
      thrombin into the aneurysm sac. The patient subsequently developed chronic
      abdominal pain, diarrhea, and a weight loss of 20 lbs. Colonoscopy revealed
      ischemic colitis of the rectosigmoid colon. Duplex evaluation indicated a patent
      superior mesenteric artery and IMA distal to its origin. Medical treatment failed
      and the patient underwent a low anterior resection 2 months later (4 months post
      EVAR). Subsequently, the aneurysm has decreased to 5.4 cm, with no evidence of
      endoleak at 1 year. We conclude that ischemic colitis may occur following
      translumbar thrombin injection. Thrombin embolization into the rectosigmoid
      arcade via the IMA was most likely the cause in this case. This problem can
      potentially be avoided by treating the IMA endoleak outflow prior to translumbar
      thrombin injection of the aneurysm sac. Thorough arteriographic evaluation of
      endoleaks should be performed prior to any interventions.

PMID- 14712381
TI  - Analysis of options for mitigating hemodialysis access-related ischemic steal
      phenomena.
AB  - Steal phenomena associated with brachial bridge grafts for hemodialysis access
      may compromise blood flow to the forearm. This work is designed to investigate
      and compare, by means of a simple mathematical model, the potential of six
      surgical procedures to alleviate steal. A flow model based on an electrical
      analogue was developed. An untapered 6-mm prosthetic brachial-axillary access
      (PBAA) was selected as the prototype configuration, and the theoretical effect of
      six access modifications on forearm flow was analyzed. Major simplifications
      include the use of Poiseuille's law for estimating arterial resistance and
      ignoring the contribution of collateral circulation. Intra-operative flow
      measurements using a Transonic flowmeter were obtained in two individuals
      undergoing treatment for a steal syndrome. The flow model predicts that the
      greatest increase in distal flow is achieved by the distal revascularization
      interval ligation (DRIL) procedure, followed by a 6-mm axillobrachial artery
      bypass graft without interval ligation, the conversion of the PBAA to an axillary
      axillary loop access, and the conversion to an axillary-brachial access. Intra
      operative measurements in two patients agreed closely with theoretical
      calculations. A simple flow model provides a tractable framework for comparing
      procedures designed to avoid or treat steal phenomena. Distal revascularization
      without interval ligation and the conversion of a PBAA to an axillary-axillary
      loop access or an axillary brachial access can be effective alternatives to the
      DRIL procedure in selected clinical settings.

PMID- 14712382
TI  - Left iliac artery thrombosis during anterior lumbar surgery.
AB  - To determine the incidence of left iliac artery thrombosis (LIAT), a prospective
      database was maintained on 1315 patients undergoing anterior lumbar surgery (ALS)
      between August 1997 and December 2002. All had distal pulse evaluation
      preoperatively. In the last 629 cases pulse oxymetry was used to monitor the
      distal circulation during and after surgery. Patients with pulse deficits or
      evidence of ischemia after surgery were further analyzed. Six patients were
      identified with LIAT (0.45%). Five were females and one was male, with ages
      ranging from 35 to 56 years. All had exposure at the L4-5. Five were diagnosed at
      surgery and one in the recovery room after posterior surgery. All except one had
      strong, palpable preoperative pulses. Pulse oxymetry confirmed the diagnosis in
      two patients, in whom it was not clinically evident. Four had successful
      thrombectomy; one had a femoro-femoral bypass and one had an axillo-femoral
      bypass. Two developed compartment syndrome. None had calcifications on
      preoperative X-rays. LIAT is an uncommon complication of ALS. Early
      identification and management can avoid long-term complications. Pulse oxymetry
      helps in its timely identification. Patients undergoing exposure at L4-5 and
      females are at greater risk.

PMID- 14712385
TI  - 8th International Congress on Amino Acids and Proteins. Rome, Italy, September 5
      9, 2003. Abstracts.

PMID- 14712386
TI  - Two asymmetric contoured plate-rods for occipito-cervical fusion.
AB  - The author presents a retrospective clinical study addressing the outcome after
      posterior stabilisation of the occipital-cervical spine using a new cranio-spinal
      implant. The range of surgical methods for operative treatment of occipito
      cervical instability remains wide, and it is still a demanding technique that
      frequently requires improvisation by the surgeon. No previous studies have been
      published of occipito-cervical reconstructions using two contoured asymmetrical
      occipital plates interdigitating in the midline at the occiput and allowing
      various methods of cervical fixation, by means of different hooks, a claw device
      or screws. Nine patients with severe occipito-cervical instability and/or
      subaxial malalignment underwent reconstructive surgery with the new implants
      between 1998 and 2001. Seven patients suffered from rheumatoid arthritis (RA)
      including cranial settling. Two patients had widespread cervical metastases. All
      patients suffering RA were treated by preoperative cervical traction for up to 28
      days, and intraoperative traction, to try to restore the malalignment. Traction
      was also used, to diminish pain and to improve neurological symptoms. The lowest
      vertebra fused was T3. All patients were immobilised with an external orthosis or
      brace for 6 weeks or 3 months. A solid fusion was achieved in all patients. None
      of the patients deteriorated postoperatively. No serious complications occurred.
      One occipital screw broke and one hook loosened, needing a re-fixation. The
      simplicity of applying these cranio-cervical implants makes them practical for
      every orthopaedic or neurosurgeon with a special interest in cervical spine
      surgery.

PMID- 14712388
TI  - Surgical treatment of pancreatic insulinomas in the era of laparoscopy.
AB  - BACKGROUND: Laparoscopic resection has been increasingly reported for pancreatic
      insulinomas. This report evaluates our experience with surgical treatment for
      pancreatic insulinomas in this era of laparoscopy and reviews the application,
      safety, and outcome of this surgical approach reported in the literature.
      METHODS: In a consecutive series of 10 patients with pancreatic insulinomas,
      laparoscopic resection was performed for selected patients after routine
      preoperative localizations. The outcome of this operative strategy was reviewed
      together with reported cases involving laparoscopic resection of pancreatic
      insulinomas. RESULTS: Laparoscopic distal pancreatectomy or enucleation was
      performed for four patients with tumors located at the body or tail of the
      pancreas, whereas open enucleation was performed for six patients with tumors
      located at the pancreatic head. Pancreatic leak developed in one laparoscopic and
      two open enucleations. A review of reported cases in the literature showed that
      61 of 69 attempted laparoscopic pancreatic resections for insulinomas were
      performed successfully. All except two tumors were located at the body or tail of
      the pancreas. For 42 cases with detailed information, 41 tumors at the pancreas
      body or tail were removed successfully by enucleation (n = 24) or distal
      pancreatic resection (n = 17), and one tumor at the pancreatic head was
      enucleated successfully. Pancreatic fistula, the most frequent complication,
      occurred in 8 (19%) of 42 laparoscopic resections. CONCLUSIONS: Laparoscopic
      resection of pancreatic insulinomas is safe and feasible for tumors located at
      the body or tail of the pancreas. Its application for tumors located at the
      pancreatic head needs further evaluation.

PMID- 14712389
TI  - How should Barrett's ulceration be treated?

PMID- 14712390
TI  - Laparoscopic treatment of choledocholithiasis using modified biliary stents.
AB  - BACKGROUND: When common bile duct (CBD) stones are present, the laparoscopic
      approach is widely used. For postoperative biliary decompression, T-tube
      insertion is the most traditional method. Antegrade biliary stenting is another
      method that could eventually replace the T-tube. METHODS: This study involved 86
      patients with CBD stones who underwent laparoscopic CBD exploration. A simple
      modification was made to the biliary stent by eliminating the proximal flap, and
      we adopted this as a routine biliary decompression device. This modified biliary
      stent (MBS) was inserted in 50 patients (MBS group), and the T-tube was used for
      36 patients (T-tube group). RESULTS: The mean operative time and the overall
      complication rate were similar between the two groups. There was no mortality.
      The mean hospital stay was significantly shorter for the MBS group. Biliary
      stents were eliminated spontaneously via the gastrointestinal tract among 36
      (81.8%) patients, and for 8 patients, the stents had to be removed
      endoscopically. Six patients were lost to follow-up evaluation. The mean time
      that elapsed until spontaneous stent elimination was 11.5 +/- 9.5 days.
      CONCLUSIONS: Among the different methods of biliary decompression, MBS renders
      the patients free of an uncomfortable T-tube. Morbidity and even mortality
      associated with T-tubes are eliminated, and the hospital stay may be shortened.
      Therefore, for selected patients, the modified biliary stent may be a better
      option than the traditional T-tube.

PMID- 14712391
TI  - Tuning host specificity during the ontogeny of a fish ectoparasite: behavioural
      responses to host-induced cues.
AB  - The choice between two alternative hosts, brown trout (Salmo trutta) and roach
      (Rutilus rutilus), and the response to visual and olfactory cues were studied in
      the ontogeny of Argulus coregoni. The initial preference of the smallest
      parasites for brighter roach changed at the age of 2 weeks, at the size of about
      2 mm, for trout, a typical salmonid host. Younger argulids were attracted by a
      non-specific visual stimulus (white disc over dark background), and they did not
      respond to olfactory stimulation (fish-conditioned water). Later, the response to
      visual stimuli was modulated by trout-conditioned water, but not by that
      conditioned by roach. The primary role of vision, particularly in early ontogeny,
      is emphasized as an adaptation of A. coregoni to habitats in boreal latitudes,
      clear and running water with a sparse fish population. In sub-adult and adult
      parasites, vision is complimented by olfaction that enables them to choose hosts
      more precisely. The nature and adaptive significance of the ontogenetic shift in
      host choice by A. coregoni is discussed.

PMID- 14712392
TI  - New morphological data on Cheilospirura hamulosa (Nematoda, Acuarioidea) by means
      of bright-field and scanning electron microscopy.
AB  - This study reports on the morphology and morphometry of the nematode
      Cheilospirura hamulosa on the basis of bright-field and scanning electron
      microscopy. Specimens were recovered after necropsies of 28 Brazilian ring-necked
      pheasants ( Phasianus colchicus) and 30 domestic chickens ( Gallus g. domesticus)
      from backyard flocks. Measurements relate to the buccal capsule in the males and
      the distance of the excretory pore from the anterior end in both sexes, while the
      vulva and ovijector are studied for the first time. The most important taxonomic
      characters for the diagnosis of this nematode are the four long, longitudinal
      cordons which are neither anastomosed nor recurrent. They are composed of a
      groove with margins formed by cuticular specializations that change in appearance
      and width backward along the body and which run backward from the cephalic region
      ending near the posterior end as a cuticular depression. According to their
      morphology, these cordons could probably have nutritional, attachment and/or
      sensory functions.

PMID- 14712393
TI  - Profilin inhibits pollen tube growth through actin-binding, but not poly-L
      proline-binding.
AB  - Previously, we have shown that excess profilin inhibits pollen tube growth at
      significantly lower concentrations than it blocks cytoplasmic streaming. To
      elucidate the mechanism by which profilin achieves this function, we have
      employed mutant profilins from Schizosaccharomyces pombe [J. Lu and T.D. Pollard
      (2001) Mol Biol Cell 12:1161-1175], which have defects in actin-binding, ability
      to inhibit polymerization, and poly- l-proline (PLP)-binding. Using Lilium
      longiflorum L. pollen and S. pombe profilins as wild-type (wt) standards, mutant
      profilins have been injected into pollen tubes of Lilium, and examined for their
      effects on growth rate and cell morphology. Our results show that mutant Y5D (68%
      actin-binding; 1.1% PLP-binding) is indistinguishable from wt-standard profilins.
      However mutant K81F (2.7% actin-binding; 77% PLP-binding) and especially mutant
      K67E (<1% actin-binding; 100% PLP-binding) are significantly less effective than
      wt-standard profilins in their ability to inhibit pollen tube growth. PLP also
      inhibits pollen tube growth. However, PLP is not different from K67E/PLP
      combined, which has no actin-binding, suggesting that PLP does not function by
      binding to profilin. In addition, there are differences in the morphology and F
      actin organization in cells injected with PLP versus wt-profilin. Whereas wt
      profilin causes a fragmentation and marked reduction in the amount of F-actin [L.
      Vidali et al. (2001) Mol Biol Cell 12:2534-2545], PLP generates an extensive
      disorganization without any apparent reduction in the amount of F-actin. We
      conclude that along with actin-binding activity of profilin, PLP-containing
      proteins also participate in the growth control process, and can do so
      independently of binding to profilin.

PMID- 14712395
TI  - Lessons from 10 years of interferon beta-1b (Betaferon/Betaseron) treatment.
AB  - In 1993, interferon beta-1b (IFN beta-1b, Betaferon/Betaseron) was the first
      interferon approved in the USA for relapsing-remitting multiple sclerosis (RRMS).
      Since then, dose-dependent effects of IFN beta in MS have been extensively
      discussed. Such effects had already been observed in the pivotal trial and were
      followed by dose comparison trials with IFN beta-1a. Later, the therapeutic
      efficacy of IFN beta-1b could also be demonstrated in secondary progressive (SP)
      MS patients. We learnt from further studies that benefit from IFN beta in SPMS
      seems to be most pronounced in those patients still having active disease with
      superimposed relapses or clear progression. The most common IFN beta-related
      adverse events, especially in the early treatment phase, have been flu-like
      symptoms and injection-site reactions. The consequent management of those as well
      as of other, less frequent, side-effects turned out to be of tremendous
      importance to ensure patients' compliance. Based on the experience of 10 years,
      IFN beta-1b belongs to the firstline therapeutics in RR and SPMS.

PMID- 14712396
TI  - Dose and frequency of interferon treatment matter--INCOMIN and OPTIMS.
AB  - Three different interferon beta (IFN beta) products are currently approved for
      the treatment of patients with relapsing-remitting multiple sclerosis (RRMS).
      However, the recommended method of administration, the dosage and the frequency
      of administration differ widely between each of the three products. Although
      controlled clinical trials have demonstrated the efficacy of both alternate-day
      IFN beta-1b (Betaferon/Betaseron) and once-weekly IFN beta-1a (Avonex) compared
      with placebo, it is likely that patient compliance, efficacy and tolerability are
      affected by the dosage regimen used. There are several issues to consider. Once
      weekly administration may be associated with fewer adverse events and greater
      convenience, and it has been suggested that this may increase compliance.
      Conversely, frequent administration may be associated with increased overall
      efficacy. There is a convincing pharmacological rationale indicating that
      frequent dosing, with an interval of less than 72 h, is necessary to sustain the
      activity of intracellular molecular signalling pathways responsible for
      regulating IFN beta-induced gene expression. However, there was a need to explore
      the overall effectiveness of the two administration protocols in a comparative
      trial. The INCOMIN (Independent Comparison of Interferon) study compared clinical
      and magnetic resonance imaging (MRI) efficacy of IFN beta-1b 250 microg (8 MIU)
      subcutaneously (s.c.) on alternate days and IFN beta-1a 30 microg (6 MIU)
      intramuscularly (i.m.) once weekly in patients with RRMS. INCOMIN demonstrated
      convincingly that clinical and MRI outcome measures were significantly better in
      the IFN beta-1b-treated group. Blinded MRI evaluation confirmed the clinical
      results. Despite some limitations of the study design, imposed by the ethical and
      practical challenges of conducting comparative trials of injectable therapies,
      the concordance of the clinical and MRI findings indicate that frequently
      administered IFN beta-1b reduced evidence of disease activity more effectively
      than once-weekly administered IFN beta-1a, with the clinical benefits for
      patients becoming more pronounced over time. Given that the response to IFN beta
      appears to be dose dependent, the question that might be asked is whether greater
      efficacy can be obtained by increasing doses beyond those currently approved.
      OPTIMS (Optimization of Interferon dose for MS) is currently examining the safety
      and efficacy of a dose of IFN beta-1b that is higher than any currently marketed
      IFN beta. While OPTIMS is still underway, preliminary safety analyses indicate
      that higher doses are well tolerated.

PMID- 14712397
TI  - Advancing treatment with interferon beta-1b (Betaferon/Betaseron) in the next
      decade--thinking beyond the standard dose.
AB  - Early therapeutic intervention with disease modifying agents in multiple
      sclerosis (MS) is recommended in an attempt to minimise damage to the central
      nervous system and improve clinical outcome. Interferon betas (IFN betas) are the
      most widely used approved therapies for MS at the present time. While optimal
      dosage and frequency of IFN administration is not fully known, evidence is
      growing that high-dose, high-frequency IFN beta may be the most effective regimen
      for controlling clinical activity and minimizing MRI lesion development for at
      least 1-2 years. Past experience demonstrates that commonly observed side-effects
      associated with IFN beta injections, such as flu-like symptoms and injection-site
      reactions, can be markedly reduced through a number of measures. Moreover, the
      incidence of these side-effects decreases with time. Taking these observations
      into account, it seems reasonable to consider increasing the maximum approved
      therapeutic dose of IFN beta-1b (Betaferon/Betaseron) in MS. It has recently been
      demonstrated that dose escalation of IFN beta-1b combined with pre-medication
      with ibuprofen enables doses as high as 500 microg every other day to be well
      tolerated. Further administration of IFN beta-1b (500 microg) in patients with
      hepatitis C revealed no safety or tolerability concerns, no unexpected or unusual
      symptoms and no relevant laboratory abnormalities during the 24-week treatment
      period. It is also noteworthy that the 500 microg dose produced a more marked
      increase in biological response markers (Mx protein) than that induced by the
      standard dose of IFN beta-1b, and that other studies have demonstrated similar
      effects on other such markers. Taken together, the available evidence provides a
      rationale for using an increased dose of IFN beta-1b in the treatment of MS. This
      will be investigated further in a new Phase III clinical trial (BEYOND).

PMID- 14712398
TI  - Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with
      inclusion body myositis-like morphology.
AB  - We reported three cases (two familial and one sporadic) of X-linked Emery
      Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients
      demonstrated a typical inclusion body myositis (IBM)-like morphology. The third
      patient had only minor changes. Patients had elbow and ankle contractures,
      progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker
      implantation in all). There was a mutation within the Xq28 gene and complete
      absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed
      vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous
      muscle inclusions were most unusual findings. Coexistence of IBM-like morphology
      and X-linked recessive EDMD might indicate that pathological features of IBM are
      nonspecific and may be present in other neuromuscular disorders.

PMID- 14712399
TI  - Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs.
AB  - Drug abuse and human immunodeficiency virus (HIV) infection seem to cause
      cumulative damage in the central nervous system (CNS). Elevated extracellular
      dopamine is thought to be a prime mediator of the reinforcing effects of
      addictive substances. To investigate the possible role of increased dopamine
      availability in the pathogenesis of HIV dementia, simian immunodeficiency virus
      (SIV)-infected monkeys were treated with dopaminergic drugs (selegiline or L
      DOPA). Both substances increased intracerebral SIV expression, combined with
      aggravation of infection-related neuropathology and ultrastructural alterations
      of dendrites in dopaminergic areas (spongiform polioencephalopathy) in
      asymptomatic animals. Moreover, this treatment resulted in enhanced TNF-alpha
      expression in the brains of SIV-infected animals. These findings indicate a
      synergistic interaction between dopamine and SIV infection on microglia
      activation, leading to increased viral replication and production of neurotoxic
      substances. Our results suggest that increased dopamine availability through
      dopaminergic medication or addictive substances may potentiate HIV dementia.

PMID- 14712401
TI  - [Radiology and general practice].

PMID- 14712400
TI  - Perinecrotic glioma proliferation and metabolic profile within an intracerebral
      tumor xenograft.
AB  - Intracerebral C6 glioma xenografts spontaneously develop centrally located
      necrotic regions that are bordered by densely packed neoplastic cells.
      Proliferative and metabolic heterogeneity in these perinecrotic regions were
      assessed by bromodeoxyuridine (BrdU) incorporation, by immunocytological and by
      histochemical analyses. The borders of necrotic regions are comprised of glioma
      cells that express increased levels of the type 1 glucose transporter (GLUT-1)
      with rare cells having incorporated BrdU. By contrast, BrdU-positive glioma cells
      are located immediately adjacent to GLUT-1-positive cells bordering areas of
      necrosis. BrdU-positive glioma cells are also scattered throughout poorly
      vascularized, central regions of the tumor and are present at the highly
      vascularized tumor periphery. GLUT-1 expression increased considerably when C6
      glioma cells were grown for 48 h under either the acidotic conditions of pH 6.8
      or under hypoxic conditions. The perinecrotic GLUT-1-positive glioma cells in
      poorly vascularized, centrally located tumor regions demonstrated a 75% reduction
      in glycogen content and negligible glycogenolytic capacity, when compared with
      normal brain white matter. Cytochrome c oxidase (COX) and lactate dehydrogenase
      (LDH) maintained 50% enzymatic activity compared to controls, while succinate
      dehydrogenase (SDH) activity was 25% of control values. Based upon these
      findings, a metabolic model is proposed in which GLUT-1-positive perinecrotic
      cells are growth arrested and predominantly rely upon non-oxidative glycolysis.
      It is further postulated that BrdU-positive, GLUT-1-negative glioma cells within
      the poorly vascularized, central tumor region convert glucose-6-phosphate to
      nucleotide precursors for DNA replication.

PMID- 14712402
TI  - MR visualization of the inner ear structures: comparison of 1.5 Tesla and 3 Tesla
      images.
AB  - AIM OF THE STUDY: To compare high resolution MRI examinations of inner ear
      structures at 1.5 T and at 3 T. METHOD: Temporal bones were measured bilaterally
      in 3 healthy volunteers in a 1.5 T and in a 3 T MR-scanner using the respective
      one channel head coil (quadrature detection) of the manufacturer. The same steady
      state gradient echo sequence (3D-CISS) was employed at a voxel size of 0.4 x 0.4
      x 0.4 mm(3). The signal-to-noise ratio (SNR) was determined quantitatively.
      RESULTS: An SNR of 8 could be achieved for the measurements at 3 T in 7:37 min.
      The SNR at 3 T was, on average, a factor of 1.34 higher than that at 1.5 T
      despite the fact that the excitation angle had to be drastically reduced (alpha =
      42 degrees instead of alpha = 70 degrees at 1.5 T) due to the limit of the
      specific absorption rate (SAR). DISCUSSION: The MR representation of the inner
      ear is clearly improved at 3 T. To obtain the same SNR at 1.5 T approximately the
      double measuring time would be required, connected with reduced patient comfort
      and an increased risk for a displacement of the head during the high resolution
      measurement.

PMID- 14712403
TI  - Sensitivity encoding (SENSE) for high spatial resolution time-of-flight MR
      angiography of the intracranial arteries at 3.0 T.
AB  - PURPOSE: 1) To evaluate feasibility of sensitivity encoding (SENSE) for high
      spatial resolution intracranial 3D time-of-flight (TOF) MR angiography at 3.0 T
      using a 1024 imaging matrix and 2) to compare image quality and diagnostic yield
      with 3.0 T TOF MRA without SENSE. METHODS: In a prospective study TOF MR
      angiography of the circle of Willis was performed with SENSE in 24 patients on a
      clinical whole body 3.0 T MR system (Intera, Philips Medical Systems, NL). In the
      SENSE protocol (S-MRA), a SENSE factor of 2.5 was used to shorten acquisition
      time and to increase the anatomic coverage (5:12 min.; 150 slices). A matrix of
      832 x 572 was acquired and reconstructed to 1024 yielding a non-zerofilled voxel
      size of 0.30 x 0.44 x 1.00 mm(3) (0.13 mm(3)). Two readers were asked to review
      the images regarding the presence of vascular disease, and to rate, in consensus,
      the quality of the angiograms on a 5-point scale (5 = excellent through 1 = non
      diagnostic). Results were compared with the results in 15 subjects who underwent
      intracranial TOF MRA at 3.0 T without SENSE (NS-MRA: acquisition time, 7:57 min.;
      100 slices). Digital subtraction angiography (DSA) served as standard of
      reference in the 4/24 patients in whom vascular disease was identified. RESULTS:
      S-MRA at 3.0 T was judged to provide image quality that was adequate for
      diagnosis or better in 24/24. Median score of image quality of S-MRA and NS-MRA
      were 5 and 5, respectively. In the 4 patients with DSA correlation, a total of 8
      pathologic findings (7 steno-occlusive diseases, 1 aneurysm) were correctly
      identified on S-MRA. CONCLUSION: The use of SENSE for intracranial TOF MRA at
      very high imaging matrix is feasible at 3.0 T. Compared to the imaging technique
      without SENSE, it allows TOF MRA with substantially reduced acquisition time, and
      with substantially increased anatomic coverage while maintaining image quality of
      NS-MRA.

PMID- 14712404
TI  - [Diagnostic value of electron-beam computed tomography (EBT). I. Cardiac
      applications].
AB  - Electron beam tomography (EBT) directly competes with other non-invasive imaging
      modalities, such as multislice computed tomography, magnetic resonance imaging,
      and echocardiography, in the diagnostic assessment of cardiac diseases. EBT is
      the gold standard for the detection and quantification of coronary calcium as a
      preclinical sign of coronary artery disease (CAD). Its standardized examination
      protocols and the broad experience with this method favor EBT. First results with
      multislice CT indicate that this new technology may be equivalent to EBT for
      coronary calcium studies. The principal value of CT-based coronary calcium
      measurements continues to be an issue of controversy amongst radiologists and
      cardiologists due to lack of prospective randomized trials. Coronary angiography
      with EBT is characterized by a high negative predictive value and, in addition,
      may be indicated in some patients with manifest CAD. It remains to be shown
      whether coronary angiography with multislice CT is reliable and accurate enough
      to be introduced into the routine work-up, to replace some of the many strictly
      diagnostic coronary catheterizations in Germany and elsewhere. Assessment of
      coronary stent patency with EBT is associated with several problems and in our
      opinion cannot be advocated as a routine procedure. EBT may be recommended for
      the evaluation of coronary bypasses to look for bypass occlusions and significant
      stenoses, which, however, can be equally well achieved with multislice CT.
      Quantification of myocardial perfusion with EBT could not replace MRI or other
      modalities in this field. EBT has proven to be accurate, reliable and in some
      instances equivalent to MRI, which is the gold standard for the quantitative and
      qualitative evaluation of cardiac function. Some disadvantages, not the least of
      which is the limited distribution of electron beam scanners, favor MRI for
      functional assessment of the heart.

PMID- 14712405
TI  - [Clinical relevance of computed tomography under emergency conditions--diagnostic
      accuracy, therapeutic consequences].
AB  - PURPOSE: To evaluate the diagnostic accuracy and therapeutic consequences of
      computed tomography performed on an emergency basis in a primary care hospital.
      MATERIAL AND METHODS: In 418 patients, 463 computed tomographies (thorax,
      abdomen, pelvis, spine, aorta, neck and extremities) were performed with-in 12
      months, providing 999 diagnoses. The computed tomography diagnoses were
      retrospectively evaluated and correlated to surgery and discharge diagnoses.
      Therapeutical consequences were analyzed and allocated to a time period < 36 h
      (urgent) and > or = 36 - 72 h (elective). Average age was 49 (1 - 94) years (41%
      female and 59% male). Discharge diagnosis was defined as gold standard, provided
      that it was supported by clinical, blood chemical, diagnostic and possible
      surgical data. RESULTS: In 176 of 999 diagnoses (18%), the diagnoses were
      classified as "non-correlatable". Of the 823 correlated diagnoses, 431 were true
      positive, 14 false positive, 66 false negative and 312 true negative.
      Sensitivity, specificity and diagnostic accuracy of computed tomography was 87,
      96 and 90%. Computed tomography had therapeutic consequences (surgery, drainage,
      puncture, reposition, thrombolytic therapy, chemotherapy, bronchoscopy,
      endoscopy, percutaneous transluminal angioplasty, coiling etc.) in 57% and no
      direct therapeutic interventions in 43%. Computed tomography excluded the
      suspected diagnosis in 36% and resulted in a conservative therapeutic regiment in
      7%. Surgery was performed on 134 of the 418 patients (32%) who underwent computed
      tomography, with the surgery urgent in 71 (17%) and elective in 63 (15%) of the
      418 patients. CONCLUSION: The high diagnostic accuracy and consecutive
      therapeutic consequences of computed tomography in establishing a precise, timely
      and reproducible diagnosis confirm its important role as primary diagnostic
      method on an emergency basis.

PMID- 14712406
TI  - [Inflammatory aortic arch syndrome: contrast-enhanced, three-dimensional MR
      angiography in stenotic lesions].
AB  - PURPOSE: To determine the value of contrast-enhanced, three-dimensional MR
      angiography for the evaluation of stenotic and occlusive vascular lesions in
      inflammatory aortic arch syndrome. MATERIALS AND METHODS: 14 patients with
      inflammatory aortic arch syndrome (giant cell arteritis: n = 8, Takayasu
      arteritis: n = 4, ankylosing spondylitis: n = 1 sarcoidosis: n = 1) underwent MR
      angiography of the aortic arch and the supra-aortic vessels (n = 15, 2 patients
      were examined twice) and of the abdominal aorta (n = 2). MRA was performed using
      a 3D-FLASH sequence (TR/TE 4.6/1.8 ms, flip angle 30 (3)) on a 1.5T system. MRA
      imaging was compared with the findings of DSA, which served as gold standard.
      RESULTS: In a total of 467 examined vascular territories, DSA revealed 50
      stenoses and 35 occlusions. All lesions were detected by MRA. In 23 segments, the
      degree of stenosis was overestimated by MRA. Sensitivity and specificity of MRA
      were 100 % and 94.3 %, positive and negative predictive values were 73.6 and 100
      %, and the accuracy was 95.1 %. CONCLUSIONS: Despite a tendency to overestimate
      stenoses, contrast-enhanced three-dimensional MR angiography is a valid, non
      invasive technique in the assessment of inflammatory aortic arch syndrome.

PMID- 14712407
TI  - [Non-invasive, multi detector row (MDR) CT based computational fluid dynamics
      (CFD) analysis of hemodynamics in infrarenal abdominal aortic aneurysm (AAA)
      before and after endovascular repair].
AB  - PURPOSE: Simulation, description and analysis of dynamic pressure in infrarenal
      abdominal aortic aneurysms (AAA) before and after endovascular repair. MATERIALS
      AND METHODS: During March 1996 and May 2001, 13 patients with AAA underwent
      endovascular treatment. The MDR-CT scans of these patients were used for the non
      invasive analysis of the hemodynamics in the aorta with CFD software before and
      after endovascular repair. One pre-interventional and three post-interventional
      CT scans were analyzed for each patient. RESULTS: Compared to the pre
      interventional simulation, endovascular treatment led to an average dynamic
      pressure decrease of 1057 Pa in 10 of 13 patients. During the subsequent course,
      the median of the dynamic pressure decreased in 8 of 13 patients. Vulnerable
      regions initially identified as high-pressure regions, like the docking area or
      the second stent limb, adapted to the pressure in the surrounding tissue in the
      course of time. CONCLUSION: CFD-based blood flow simulation offers the
      opportunity to analyze dynamic pressure in AAA before and after endovascular
      repair and allows a prognostic statement as to the possible homogenization of the
      pressure in abdominal stent-grafts.

PMID- 14712408
TI  - [Contrast-enhanced MR angiography (CEMRA) in peripheral arterial occlusive
      disease (PAOD): conventional moving table technique versus hybrid technique].
AB  - PURPOSE: In peripheral arterial occlusive disease (PAOD), angiographic evaluation
      of the entire aortopedal arterial system is mandatory. In a randomized study, two
      different protocols of CEMRA were evaluated prospectively to compare their
      diagnostic quality and clinical usefulness. PATIENTS AND METHODS: 80 patients
      (males n = 60, females n = 20, median age = 70 years, diabetics n = 27) with PAOD
      were examined with a 1.5 T system (40 mT/m) using a dedicated phased array
      peripheral vascular coil. Protocol A consisted of a single injection of Gd-BOPTA
      with consecutive craniocaudal image acquisition and protocol B of two injections,
      with the first injection of Gd-BOPTA followed by image acquisition of the
      popliteocrural and pedal segments and the second injection followed by acquiring
      the aortoiliac and femoral segments (hybrid technique). The evaluation of the
      arterial system was directed to the iliac, femoral, popliteocrural and pedal
      arteries. RESULTS: The visualization of the entire aortopedal vascular system was
      of diagnostically good or satisfactory quality in 16 of 40 patients using
      protocol A and in 29 of 40 patients using protocol B (iliac 40 vs. 37, femoral 40
      vs. 40, popliteocrural 35 vs. 37, pedal 16 vs. 29); without the pedal station the
      number increased to 35 of 40 patients for both protocols. The reason of
      diagnostic limitations was an arteriovenous overlap in 24 of 80 cases, with 19 of
      40 cases for protocol A and 5 of 40 for protocol B, located exclusively in the
      cruropedal region. CONCLUSION: Moving table hybrid CEMRA is superior to
      conventional technique in craniocaudal direction by producing less venous overlap
      of arteries and is especially more suitable for the diagnostic evaluation of the
      cruropedal region.

PMID- 14712409
TI  - [Initial clinical experience with a new percutaneous peripheral atherectomy
      device for the treatment of femoro-popliteal stenoses].
AB  - BACKGROUND: Evaluation of the efficacy and safety of a new 7F-atherectomy device
      (30-day endpoint) for the treatment of short and mid-length arterial lesions with
      a reference diameter of 2.5-7 mm. MATERIAL AND METHODS: Fifty-eight femoto
      popliteal stenoses in 46 patients (67% male, mean age 66 +/- 9 years) with
      chronic peripheral occlusive disease of the lower limbs [Rutherford stage 2: n =
      13 (28%); stage 3: n = 29 (63%), stage 4: 2 (4%), stage 5: n = 2 (4%)], were
      treated with directional atherectomy. Target lesion characteristics: Common
      femoral artery: n = 1 (2%), superficial femoral artery: n = 47 (81%); popliteal
      artery, n = 10 (17%); in stent n = 3 (5 %). Thirty (65 %) of the interventions
      were performed using an antegrade approach, 16 (35%) interventions in cross-over
      technique. Mean degree of stenosis was 83 +/- 11 mm, mean length of lesion was 37
      +/- 37 mm. RESULTS: 6.5 +/- 2 (4-10) passes of the lesion were performed with the
      catheter. Three lesions were treated after predilatation, 55 (95%) interventions
      as primary atherectomy. In 31/58 lesions (53%) additional balloon angioplasty was
      performed, in 1 lesion (2%) additional stent placement was needed. The mean
      degree of stenosis after atherectomy was reduced to 29 +/- 20% (0-60%) after
      additional balloon angioplasty, it was 11 +/- 10% (0-30 %). A residual stenosis
      of < 50% after plain atherectomy was achieved in 55 (95%) lesions, of < 30% in 49
      (84%). COMPLICATIONS: 3 (6.5%) cases of embolism of debris were detected and
      treated successfully by aspiration. The mean ankle-brachial index increased from
      0.62 +/- 0.12 to 0.92 +/- 0.36 before discharge, and to 0.86 +/- 0.17 after 30
      days. Rutherford stage after 30 days: stage 0: n = 038 (83%); Stage 1: n = 4
      (8%); Stage 2: n = 3 (6%); Stage 5: n = 1 (2%). CONCLUSION: Lesions up to 8 cm in
      length of the femoropopliteal arteries can be treated successfully in most cases
      with the new atherectomy catheter. Embolism, the only complication that occurred,
      can be avoided by cleaning the nose cone after at least 4 passes of the lesion.

PMID- 14712410
TI  - [Early prediction of treatment response to high-dose chemotherapy in patients
      with relapsed germ cell tumors using [18F]FDG-PET, CT or MRI, and tumor marker].
AB  - PURPOSE: To assess the ability of [(18)F]FDG-PET, CT/MRI and serum tumor marker
      (TM) for the early prediction of response in patients with metastatic germ cell
      tumors (GCT) undergoing salvage high-dose chemotherapy (HD-CTX). MATERIALS AND
      METHODS: Before commencement of HD-CTX, 19 patients with metastases from GCT were
      evaluated with [(18)F]FDG-PET, CT or MRI and TM after 2-3 cycles of induction
      chemotherapy and the results compared with those of the baseline examinations.
      PET was analyzed visually and quantitatively by calculating the standard uptake
      value (SUV). CT or MRI was evaluated for changes in tumor size (progressive
      disease/stable disease PD/SD = viable lesion; partial remission/complete
      remission PR/CR = nonviable lesion), density or signal intensity, homogeneity and
      contrast enhancement. For the prognosis, the worse case, i.e., the most vital
      lesion detected in a patient, was considered. The reference standard was the
      result of the histology after resection of any residual masses (N = 10) and/or
      the clinical-radiological follow-up for at least 6 months after completion of the
      treatment (N = 9). RESULTS: Six of nineteen patients (32 %) remained progression
      free for over 6 months following treatment, whereas 13 (68 %) progressed. The
      outcome of HD-CTX was correctly predicted by PET, CT and TM in 89 %, 67 % and 88
      %, respectively. In 5 of 6 patients with successful HD-CTX, PET was negative
      (mean SUV = 1.8), with CT or MRI showing a partial regression of the tumor in 4
      of 5 patients. Of the 13 patients not cured by HD-CTX, the PET data were positive
      in all (mean SUV = 2.7), and the CT/MRI results were true positive (PD or SD) in
      8 and false negative (PR) in 5 patients. The combined assessment of CT and TM
      corrected 3 false negative prognoses and 1 false positive CT prognosis. Two
      patients with unfavorable outcome despite a favorable response by CT and TM
      criteria were exclusively identified by PET. The resultant sensitivities and
      specificities for the prediction of therapy response are as follows: PET 100% and
      67%; CT/MRI 62% and 80%; TM 83% and 100%; CT+TM 85% and 83%. CONCLUSION: FDG-PET
      has a high prognostic value for predicting the response to chemotherapy in
      patients with metastatic GCT early in the course of treatment and may improve
      patient selection for subsequent HD-CTX protocols. Especially in patients with
      response to induction chemotherapy according to CT or TM evaluation, PET offers
      additional information to detect patients with an overall unfavorable outcome.

PMID- 14712411
TI  - [1-molar Gadobutrol as a contrast agent for digital subtraction angiography].
AB  - PURPOSE: To evaluate one-molar Gadobutrol solution as contrast media for intra
      arterial digital subtraction angiography (DSA). MATERIALS AND METHODS: In 10
      patients (7 males, 3 females; mean age 68 years) with contraindications for the
      use of iodinated contrast media (n = 8 renal insufficiency, n = 2 previous
      allergic reaction), Gadobutrol solution (1 mol/l) was used as contrast media for
      DSA. Six diagnostic angiograms and four DSAs for percutaneous transluminal
      angioplasty (PTA) were performed. RESULTS: In all cases, Gadobutrol yielded
      sufficient contrast for diagnostic DSA. Because of dose limitations (maximum 0.3
      ml/kg body weight), small amounts of iodinated contrast media were administered
      to complete the angiographic procedure (mean 15 ml) in two patients. Allergic
      reactions were not recorded in any patient. In patients with pre-existing renal
      insufficiency, mean serum creatinine level was not statistically significant
      different from the initial level (mean 2.88 mg/dl before and 2.83 mg/dl after
      DSA). Selective injection of Gadobutrol resulted in temporary discomfort.
      CONCLUSION: One molar Gadobutrol is an alternate contrast media for DSA in
      patients with contraindications for iodinated contrast media. Current dose
      limitations require selective injections.

PMID- 14712412
TI  - [Increased signal intensity of velocity measurements in duplex sonography by
      using the contrast agent levovist: a prospective, randomized study in a fetal
      sheep model].
AB  - PURPOSE: To evaluate the potential diagnostic advantages of the contrast agent
      Levovist for signal enhancement of small adjoining fetal vessels and to study the
      effect of Levovist before and during acute fetal hypoxia on the fetal circulation
      and the fetal blood flow velocities. MATERIALS AND METHODS: A prospective,
      randomized study was performed in 12 fetal sheep before and during acute fetal
      hypoxia produced by complete occlusion of the maternal common iliac artery. Two
      groups of animals were studied, comprising animals with (study group, n = 6) and
      without (control group, n = 6) Levovist. In the study group, Levovist was
      administered intravenously by a pump (modified IVAC P 4000, Schering, Berlin).
      Duration and intensity of signal enhancement were measured in the fetal aorta,
      the common carotid artery and the ophthalmic artery of both groups before and
      during hypoxia. Concurrently, fetal heart rates as well as systolic and diastolic
      blood flow velocities in all three vessels were recorded in both groups. RESULTS:
      The increased signal intensity of up to 15 dB in the study group resulted in
      improved differentiation and imaging quality of adjoining small fetal vessels
      when compared with the control group. Neither before nor during acute hypoxia,
      significant differences of the fetal heart rate and the systolic and diastolic
      blood flow velocities were observed between the two groups (p > 0.05). In the
      study group, no emboli were caused by Levovist in any fetal tissue or in the
      placenta. CONCLUSION: The contrast agent Levovist improves the detection and
      accuracy of monitoring flow velocities in small fetal vessels by increasing the
      intensity of the Doppler signal without affecting fetal heart rate or fetal blood
      flow velocities.

PMID- 14712413
TI  - [Does the result of thrombolysis with recombinant tissue-type plasminogen
      activator (rt-PA) in rabbits depend on the erythrocyte- and fibrin-content of a
      thrombus?].
AB  - PURPOSE: It is known from autopsy studies that thromboembolic stroke can be
      caused by red, white and mixed clots. We therefore examined whether the efficacy
      of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA)
      depends on the proportions of fibrin and erythrocytes within thromboembolic
      material. METHODS: In 23 rabbits intraarterial thrombolysis with 3 mg rt-PA/kg
      body weight was started 30 minutes after middle cerebral artery occlusion with
      either red or white autologous emboli 20 hours old. 20 rabbits served as control.
      Cerebral perfusion was monitored by MRI. RESULTS: rt-PA enhanced lysis of red but
      not of white emboli and decreased the infarct volume only if vascular occlusion
      was due to red emboli (p <.01). Cerebral perfusion improved only in the red
      treatment group where the normalized first moment (NFM) decreased (p <.05) and
      the relative regional cerebral blood volume (rrCBV) reached normal values (p
      <.05). CONCLUSION: We suggest that in our animal model the efficacy of
      thrombolysis increases with the proportion of erythrocytes within thromboembolic
      material and decreases with its content of fibrin. lf these findings would also
      be applicable to patients, pretherapeutic estimation of the efficacy of
      thrombolysis might become feasible because the CT values of red and white thrombi
      differ.

PMID- 14712414
TI  - [Multislice CT of the pelvis: dose reduction with regard to image quality].
AB  - PURPOSE: To optimize the examination protocols of multislice CT (MSCT) of the
      pelvis for dose reduction with regard to image quality. MATERIALS AND METHODS:
      MSCT of the pelvis was performed on 5 cadaver specimens with stepwise reduction
      of the tube current at 140 kV (250, 200, 150, 100, 75, 50, 35, 25 mAs) and 120 kV
      (50, 27 mAs). The remaining scan parameters like collimation (4 x 1 mm) and table
      speed of 4 mm per rotation remained unchanged. Axial sections and coronal
      reconstructions were used to evaluate cortex, trabecular structures, subjective
      image quality, image noise and detail detectability (pelvis and SI joint), with
      evaluation performed independently by four blinded experienced radiologists on a
      5-point scale. Kappa coefficient, accuracy of the observers to sort the films
      with regard to dose reduction and mean scores of image evaluation were determined
      for statistical analysis. RESULTS: The deterioration of the image quality was
      most pronounced for all criteria between 75 mAs and 50 mAs at 140 kV. Good
      results with adequate image quality were obtained for detail detectability at 50
      mAs and 140 kV (effective dose [E]: 3.3 mSv) and for the remaining four criteria
      at 75 mAs (E: 4.9 mSv). There was a moderate agreement between the four observers
      (kappa coefficient: 0.27). All observers were excellent in arranging the images
      according to the increasing dose reduction. CONCLUSIONS: Image quality of MSCT of
      the pelvis appears to be acceptable at 75 mAs and 140 kV with the dose reduced to
      46% of the average value of the nation-wide survey of the German Roentgen Society
      in 1999 for this type of examination.

PMID- 14712415
TI  - [Investigation of the entrance dose of standardized chest radiographs].
AB  - In 50 chest radiographs obtained in PA projection with the patient erect and the
      radiographic techniques kept constant, entrance dose, entrance surface dose and
      dose area product were measured and compared with the measurements obtained with
      Plexiglas and Alderson phantoms. Following the recommendations of the
      International Commission on Radiological Protection, the "absorbed dose in air"
      at the point of intersection of the X-ray beam with the surface of the patient
      was used as reference. For patients with the same diameter, the measured dose
      deviated up to +/- 50 % from the "Reference Man" according to the ICRP 23 as well
      as from the "Representative Patient" according to the ICRP 73. The exposure data
      produced by the equipment corresponded to the measured values with minor
      deviations, but the dose values expressed as entrance surface dose showed major
      deviation in comparison with the entrance dose due to differences in the back
      scatter factor. The values of entrance dose calculated from the dose area product
      measurements showed additional uncertainties due to different field sizes.
      Moreover, a sex-specific dose area product value was identified. These results
      reveal that the values of the "ICRP Reference Man" differ in many situations from
      the values produced by the examined patient due to differences in radiation
      transmission. This has consequences for determining diagnostic reference values
      and investigating recorded radiation exposure. This will be explained and
      substantiated.

PMID- 14712416
TI  - [Tumor staging with PET/CT. Detection of a second tumor].

PMID- 14712417
TI  - [The AV-malformation of the uterus: a rare cause of dysmenorrhea and
      menometrorrhagia].

PMID- 14712418
TI  - [Thoracic wall crossing (pseudo-?) tumor in a child: abscess-forming thoracic
      actinomycosis caused by Actinomyces meyeri et israeli].

PMID- 14712419
TI  - [Duplication of A. cerebri media in multiple intracranial aneurysms].

PMID- 14712420
TI  - Comparative genomics and the evolution of human mitochondrial DNA: assessing the
      effects of selection.
AB  - This article provides evidence that selection has been a significant force during
      the evolution of the human mitochondrial genome. Both gene-by-gene and whole
      genome approaches were used here to assess selection in the 560 mitochondrial DNA
      (mtDNA) coding-region sequences that were used previously for reduced-median
      network analysis. The results of the present analyses were complex, in that the
      action of selection was not indicated by all tests, but this is not surprising,
      in view of the characteristics and limitations of the different analytical
      methods. Despite these limitations, there is evidence for both gene-specific and
      lineage-specific variation in selection. Whole-genome sliding-window approaches
      indicated a lack of selection in large-scale segments of the coding region. In
      other tests, we analyzed the ratio of nonsynonymous-to-synonymous substitutions
      in the 13 protein-encoding mtDNA genes. The most straightforward interpretation
      of those results is that negative selection has acted on the mtDNA during
      evolution. Single-gene analyses indicated significant departures from neutrality
      in the CO1, ND4, and ND6 genes, although the data also suggested the possible
      operation of positive selection on the AT6 gene. Finally, our results and those
      of other investigators do not support a simple model in which climatic adaptation
      has been a major force during human mtDNA evolution.

PMID- 14712421
TI  - Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with
      chronic kidney disease: a meta-analysis of randomized, controlled trials.
AB  - BACKGROUND: Radiocontrast nephropathy (RCN) is a common cause of hospital
      acquired acute renal failure. Results of several studies using N-acetylcysteine
      (NAC) for the prevention of RCN have yielded conflicting results. We performed a
      meta-analysis of group data extracted from previously published studies to assess
      the effect of NAC on the prevention of RCN in patients with pre-existing chronic
      kidney disease (CKD). METHODS: Ovid's multidatabase search for MEDLINE, Cochrane
      Central Registry of Controlled Trials, Cochrane Database of Systematic Reviews,
      and HealthSTAR were used to identify candidate articles. Abstracts from
      proceedings of scientific meetings also were screened. We selected blinded and
      unblinded randomized controlled trials (RCTs) performed in humans 18 years and
      older with pre-existing CKD, defined by a mean baseline serum creatinine level of
      1.2 mg/dL or greater (> or =106.1 micromol/L) or creatinine clearance less than
      70 mL/min (<1.17 mL/s). The overall risk ratio (RR) for the development of RCN
      was computed using a random-effects model. RESULTS: Eight RCTs (n = 885 patients)
      published in full-text articles were included in the primary analysis. In the
      control group, the overall rate of RCN was 18.5% (95% confidence interval [CI],
      15 to 22). In the primary analysis, overall RR for RCN associated with the use of
      NAC was 0.41 (95% CI, 0.22 to 0.79; P = 0.007). In a sensitivity analysis that
      included 4 additional RCTs published in abstract form, RR remained significant at
      0.55 (95% CI, 0.34 to 0.91; P = 0.020). CONCLUSION: NAC reduces the risk for RCN
      in patients with CKD.

PMID- 14712422
TI  - Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental
      glomerulosclerosis.
AB  - BACKGROUND: The therapy of nephrotic syndrome in focal segmental
      glomerulosclerosis (FSGS) is still a matter of controversy. METHODS: We performed
      a prospective randomized study of the treatment of nephrotic syndrome due to
      FSGS. We compared 2 specific treatment protocols to assess the effect of
      treatment on proteinuria and renal function. Fifty-seven patients were randomly
      assigned to 2 groups: group 1 (n = 34) received steroids and cyclosporine, and
      group 2 (n = 23) received steroids and chlorambucil for 6 months. When treatment
      was refractory to chlorambucil, the patients in this group were treated with
      cyclosporine. Creatinine, blood urea nitrogen, proteinuria, lipids, and arterial
      hypertension were monitored at regular intervals. RESULTS: Patients showed a mean
      serum creatinine of 1.5 +/- 0.2 mg/dL (132.6 +/- 17.7 micromol/L) and proteinuria
      of 4.8 +/- 2.8 g/24 h with no differences between the groups. At the end of the
      chlorambucil therapy, patients in group 2 had creatinine levels of 1.8 +/- 0.6
      mg/dL (159.1 +/- 53 micromol/L) and proteinuria levels of 3.4 +/- 1 g/24 h. All
      patients in this group were given cyclosporine. After 4 years the mean creatinine
      level in group 1 was 1.7 +/- 0.4 mg/dL (150.3 +/- 35.4 micromol/L) and the
      proteinuria level was 2.5 +/- 1 g/24 h. In group 2, the mean creatinine level was
      1.9 +/- 0.6 mg/dL (168 +/- 53 micromol/L) (not significant [NS]) and the mean
      proteinuria level was 2.3 +/- 1.1 g/24 h (NS). Full remission occurred in 23% of
      the patients in group 1 (n = 8) and 17% of the patients in group 2 (n = 4; NS).
      Partial remission was observed in 38% of the patients in group 1 (n = 13) and 48%
      in group 2 (n = 11; NS). The number of patients who developed end-stage renal
      disease was comparable in both groups: 4 of 34 patients in group 1 after 2.5 +/-
      0.8 years, and 5 of 23 patients in group 2 (NS). CONCLUSION: Additional treatment
      with chlorambucil was found to be ineffective in FSGS. Patients responded to
      treatment with steroids or cyclosporine, but additional treatment with
      chlorambucil did not improve the patient's outcome. Future studies must focus on
      the long-term prognosis of these patients.

PMID- 14712423
TI  - Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of
      focal segmental glomerulosclerosis.
AB  - BACKGROUND: Podocyte injury may induce podocyte proliferation, which results in
      glomerular scarring. The cellular lesion, seen in some patients with primary
      focal segmental glomerulosclerosis (FSGS), is characterized by proliferation of
      cells covering the sclerotic or collapsed glomerular tufts. Cell-cycle mechanisms
      by which podocyte proliferation occurs in the cellular lesion of FSGS are
      unclear. METHODS: We examined expression patterns of cyclin D1; cyclin E; cyclin
      A; cyclin B1; cyclin-dependent kinase (CDK)2; CDK4; such CDK inhibitors as
      p21WAF1/CIP1 (p21), p27kip1 (p27), and p57kip2 (p57); and Wilms' tumor protein-1
      (WT-1) in 12 renal biopsy specimens with the cellular lesion of FSGS and 6 renal
      biopsy specimens with no detectable abnormalities by immunohistochemistry and
      immunoelectron microscopy. Messenger RNA (mRNA) expression patterns of cyclin D1,
      cyclin E, p21, p27, and p57 were evaluated further by in situ hybridization.
      RESULTS: In controls, immunostaining for cyclin A, cyclin B1, CDK2, CDK4, and p21
      was almost negligible, but positive signals for cyclin D1, cyclin E, p27, and p57
      were observed in glomerular epithelial cells (GECs). In the cellular lesion of
      FSGS, positive signals for cyclin E, cyclin A, cyclin B1, CDK2, and p21 were
      present in GEC nuclei, in which WT-1, p27, p57, and cyclin D1 were undetected.
      Immunoelectron microscopy showed that cyclin E-, CDK2-, and p21-specific gold
      particles were increased significantly in GEC nuclei in the cellular lesion in
      which cyclin D- and p57-specific particles were absent compared with controls. An
      in situ hybridization study showed specific signals of cyclin D1, cyclin E, p21,
      p27, and p57 mRNA in GECs forming the cellular lesion of FSGS. CONCLUSION: Our
      results suggest that damaged podocytes may inhibit p27 and p57 protein
      expression, but activate a cyclin D1-independent cell-cycle mechanism and mitotic
      cell cyclins to promote GEC proliferation in the cellular lesion of FSGS.

PMID- 14712424
TI  - Antiphospholipid antibodies are associated with an increased risk for chronic
      renal insufficiency in patients with lupus nephritis.
AB  - BACKGROUND: Previous studies have documented the high frequency of thrombosis and
      fetal loss in patients with lupus nephritis and antiphospholipid (aPL)
      antibodies, but there is little information on the impact of aPL antibodies on
      the outcome of lupus nephritis. The aims of this study are to evaluate the
      prevalence of aPL antibodies in patients with lupus nephritis and assess their
      prognostic value for thrombosis and pregnancy morbidity and impact on long-term
      renal outcome. METHODS: One hundred eleven patients with lupus nephritis followed
      up for a mean of 173 +/- 100 months were tested regularly for immunoglobulin G
      (IgG) and IgM anticardiolipin antibodies and lupus anticoagulant. RESULTS: The
      overall prevalence of aPL antibodies was 26%. In follow-up, 79% of aPL antibody
      positive patients experienced thrombotic events and/or fetal losses, and aPL
      antibodies were associated significantly with arterial or venous thrombosis (P =
      0.00001), pregnancy morbidity (P = 0.045), thrombocytopenia (P = 0.0015), and
      persistent arterial hypertension (P = 0.028). aPL antibodies were significantly
      more frequent in patients with biopsy-proven membranous lupus nephritis (P =
      0.01). A strong association between aPL antibodies and the development of chronic
      renal insufficiency in the long-term outcome also was found (P = 0.01). With
      multivariate analysis, aPL antibody positivity (P = 0.02), high plasma creatinine
      level at presentation (P = 0.01), and chronicity index (P = 0.00004) were
      independent predictors of chronic renal function deterioration. CONCLUSION:
      Detection of aPL antibodies in patients with lupus nephritis is useful not only
      to identify patients at risk for vascular and obstetric manifestations, but also
      for their potential deleterious impact on renal outcome.

PMID- 14712425
TI  - Creatinine levels and cardiovascular events in women with heart disease: do small
      changes matter?
AB  - BACKGROUND: Small changes in creatinine levels have been incrementally associated
      with increased risk for heart failure morbidity, but their association with
      cardiovascular events has not been evaluated in persons with established coronary
      heart disease (CHD). METHODS: This was an observational study from the Heart and
      Estrogen/Progestin Replacement Study (HERS) and the HERS-II follow-up study.
      Participants were 2,763 postmenopausal women with CHD who were followed up for a
      mean of 4.1 years during HERS and an additional 2.7 years during HERS-II. We
      evaluated the association of worsened renal function (creatinine level increase >
      or = 0.3 mg/dL [> or =26.5 micromol/L]) during HERS with CHD outcomes (nonfatal
      myocardial infarction and CHD death) that occurred during HERS-II. RESULTS: Only
      194 participants (9%) had worsened renal function during HERS, and they were
      characterized by a greater prevalence of diabetes, lower high-density lipoprotein
      cholesterol and higher triglyceride levels, and increased rate of cardiovascular
      events during HERS (all P < 0.01). After adjustment for only baseline creatinine
      levels, worsened renal function was associated with HERS-II CHD events (relative
      hazard [RH], 1.54; 95% confidence interval [CI], 1.04 to 2.29). After adjustment
      for baseline characteristics, HERS cardiovascular events, and medication use,
      worsened renal function was no longer associated with CHD events (RH, 1.08; 95%
      CI, 0.70 to 1.67). However, baseline creatinine levels from HERS were remarkably
      strong predictors of HERS-II events. CONCLUSION: Although baseline renal function
      was among the strongest predictors of CHD events during 7 years of HERS follow
      up, we found no significant association of worsened renal function with
      cardiovascular outcomes after adjustment for cardiovascular risk factors and
      interim events.

PMID- 14712426
TI  - The effect of long-term aggressive lipid lowering on ischemic and atherosclerotic
      burden in patients with chronic kidney disease.
AB  - BACKGROUND: Cardiac mortality is the main cause of death in patients with chronic
      kidney disease (CKD). In this study, we sought the efficacy of long-term
      intensive lipid level lowering on atherosclerotic burden in patients with CKD.
      METHODS: Patients with CKD (n = 38; age, 64 +/- 11 years) and a similar group of
      patients with coronary artery disease (CAD; n = 31) were treated prospectively
      with atorvastatin, up to 80 mg/d. Lipid profile, carotid intima-media thickness
      (IMT; a marker of atherosclerotic burden), and dobutamine echocardiography were
      measured at baseline and 2 years. Predictors of change in maximal IMT were sought
      in a linear model. RESULTS: Despite similar cholesterol level lowering, patients
      with CAD showed an improvement in maximum IMT, whereas those with CKD did not
      (mean between-group difference, 0.07 mm; 95% confidence interval, 0.01 to 0.12).
      Change in maximal IMT was associated with kidney disease (R2 = 0.09; P = 0.013),
      smoking (R2 = 0.083; P = 0.017), baseline low-density lipoprotein cholesterol
      (LDL-C) level (R2 = 0.064; P = 0.045), very low density cholesterol (VLDL-C)
      level (R2 = 0.084; P = 0.021), and calcium channel blocker use (R2 = 0.094; P =
      0.01). In a multivariate model, kidney disease and baseline LDL-C and VLDL-C
      levels remained independent predictors of change in maximal IMT (model R2 = 0.24;
      P = 0.004). Only patients with CAD decreased their number of ischemic segments
      (2.5 +/- 1.4 to 1.2 +/- 1.5 segments; P = 0.002). Overall change in ischemic
      segment number correlated with change in maximal IMT (r = 0.32; P = 0.019).
      CONCLUSION: Patients with CKD undergoing intensive lipid level lowering do not
      show the same changes in atherosclerotic or ischemic burden as patients with CAD.
      Independent predictors of change in maximal IMT were CKD and baseline LDL-C and
      VLDL-C levels.

PMID- 14712427
TI  - Protective effect of vitamins K2 and D3 on prednisolone-induced loss of bone
      mineral density in the lumbar spine.
AB  - BACKGROUND: Although vitamin K2 has been shown to prevent prednisolone-induced
      loss of bone mineral density of the lumbar spine in patients with chronic
      glomerulonephritis, the magnitude of this effect remains to be clarified. The aim
      of this prospective study is to compare the protective effect of vitamin K2 with
      that of vitamin D3 on prednisolone-induced loss of bone mineral density in
      patients with chronic glomerulonephritis. METHODS: Sixty patients (28 men, 32
      women) were randomly divided into 4 groups (n = 15 each group): control (group
      C), vitamin D3 alone (alfacalcidol, 0.5 microg/d; group D), vitamin K2 alone
      (menatetrenone, 45 mg/d; group K), and vitamins D3 plus K2 (group D + K).
      Alfacalcidol and menatetrenone therapy were started at the same time as
      prednisolone. Bone mineral density of the lumbar spine (L2 to L4) was determined
      by means of dual-energy X-ray absorptiometry, and various biochemical parameters
      of calcium and bone homeostasis were assessed before and at the end of week 8 of
      treatment. RESULTS: Treatment with prednisolone alone caused loss of bone mineral
      density, which could be fully prevented in groups D, K, and D + K. However,
      marked reductions in levels of several biochemical markers of both bone formation
      and resorption also were observed in all groups. The preventive effect in groups
      K and D + K on loss of bone mineral density induced by prednisolone was similar
      to that in group D. The elevation in serum calcium levels observed in group D was
      attenuated in group D + K. CONCLUSION: Protective effects of vitamin K2 or
      vitamins D3 and K2 on prednisolone-induced loss of bone mineral density are
      similar to that of vitamin D3.

PMID- 14712428
TI  - Protein malnutrition and hypoalbuminemia as predictors of vascular events and
      mortality in ESRD.
AB  - BACKGROUND: It is proposed that chronic inflammation is common to the
      pathogenesis of malnutrition and vascular disease, both frequently observed in
      patients with end-stage renal disease. However, previous studies were unable to
      differentiate between true protein malnutrition and hypoalbuminemia. METHODS:
      This study was undertaken to determine the associations between malnutrition,
      measured by total-body nitrogen (TBN), and albumin, a marker of both nutritional
      status and chronic inflammation, with mortality and morbidity. One hundred nine
      patients starting dialysis therapy underwent nutritional assessment (TBN level
      and anthropometric measurements), vascular risk assessment (hypertension,
      hypercholesterolemia, diabetes mellitus, and smoking status), and serum albumin
      measurement. Subsequent patient mortality and new vascular events were recorded.
      RESULTS: Survival was associated independently with both TBN (hazard ratio [HR],
      1.6; 95% confidence interval [CI], 1.1 to 2.5; P = 0.02 for every 10% decrease in
      nitrogen index) and serum albumin levels (HR, 1.1; 95% CI, 1.0 to 1.2; P = 0.004
      for every 0.1-g/dL (1-g/L) decrease in serum albumin level) adjusted for other
      variables. Only low serum albumin level predicted subsequent vascular morbidity
      (HR, 2.2; 95% CI, 1.0 to 4.9; P = 0.049), as did increasing age (HR, 2.0; 95% CI,
      1.4 to 3.0; P = 0.0004 for every 10-year increase in age) adjusted for other
      important risk factors. CONCLUSION: This study dissociates the effect of protein
      malnutrition and hypoalbuminemia on morbidity and mortality in patients starting
      dialysis therapy. Protein malnutrition and hypoalbuminemia are independently
      predictive of mortality, whereas hypoalbuminemia is predictive of vascular
      morbidity. The study supports the hypothesis that hypoalbuminemia is
      pathogenically associated with vascular disease, but dissociates this effect from
      protein malnutrition.

PMID- 14712429
TI  - Regional citrate anticoagulation for continuous venovenous hemodiafiltration
      using calcium-containing dialysate.
AB  - BACKGROUND: Regional anticoagulation with trisodium citrate for continuous
      venovenous hemodiafiltration (CVVHDF) is an effective and safe alternative to
      heparin, especially in patients at high risk for bleeding. However, regional
      citrate anticoagulation is not used widely because current protocols are complex,
      labor intensive, and cumbersome. Existing protocols require the use of calcium
      free dialysate with a continuous systemic calcium infusion to prevent
      hypocalcemia. We evaluated Anticoagulant Citrate Dextrose Formula A (ACD-A)
      solution for regional anticoagulation in CVVHDF in combination with a
      commercially available calcium-containing dialysis solution. METHODS: Thirty
      eight patients in the intensive care units underwent citrate-based CVVHDF using
      low-calcium peritoneal dialysis solution (calcium, 5.0 mg/dL [1.25 mmol/L]). ACD
      A infusion rate was adjusted to maintain postfilter ionized calcium (iCa++)
      levels at 1.0 to 2.0 mg/dL (0.25 to 0.5 mmol/L). Calcium chloride (10%) solution
      was administered intravenously every 6 hours on an as-needed basis to maintain
      systemic serum iCa++ levels at 3.5 to 4.0 mg/dL (0.88 to 1.0 mmol/L). RESULTS:
      CVVHDF was performed for a total of 394 days using 149 hemofilters. Mean
      hemofilter life span was 63.5 +/- 27.1 hours. Seventy-five percent, 61%, and 49%
      of hemofilters were patent at 24, 48, and 72 hours, respectively. No patient
      experienced a change in clinical status caused by hypocalcemia and/or signs and
      symptoms of citrate toxicity. Four patients developed metabolic alkalosis
      requiring 0.1 N of hydrochloric acid infusion. CONCLUSION: Our simplified
      technique of regional citrate anticoagulation for CVVHDF using calcium-containing
      dialysate is not associated with increased hemofilter clotting and obviates the
      need for a continuous systemic calcium infusion and calcium-free dialysate.

PMID- 14712430
TI  - Highly increased cell proliferation activity in the restenotic hemodialysis
      vascular access after percutaneous transluminal angioplasty: implication in
      prevention of restenosis.
AB  - BACKGROUND: The effect of percutaneous transluminal angioplasty (PTA) in the
      treatment of hemodialysis vascular access stenosis is attenuated by a high
      restenosis rate, which results mainly from neointimal hyperplasia. Cellular
      proliferation is one of the most important biological mechanisms involved in
      neointimal hyperplasia and may be a potential target of intervention to prevent
      restenosis. METHODS: We investigated the activity of cellular proliferation of
      restenotic lesions by means of immunohistochemistry, using an antibody to the
      proliferating cell nuclear antigen. Specimens from 10 primary stenotic and 20
      restenotic lesions of 30 Brescia-Cimino fistulae were obtained during revision.
      RESULTS: The proliferation index of the restenotic group was strikingly
      significantly greater than that of the primary stenotic group (intima, P < 0.001;
      media, P = 0.001). Proliferation indices of patients with diabetes in the
      restenotic group were significantly higher than those of patients without
      diabetes (intima, P = 0.028; media, P = 0.002). In the restenotic group,
      proliferation indices correlated negatively with the interval from PTA to
      restenosis (intima, r = -0.741; P < 0.001; media, r = -0.589; P = 0.006) and
      positively with the number of PTAs per lesion (intima, r = 0.754; P < 0.001;
      media, r = 0.506; P = 0.004). CONCLUSION: We show markedly high cellular
      proliferation activity in early restenotic lesions of arteriovenous fistulae.
      These findings indicate that adjunctive antiproliferative therapy is mandatory in
      preventing restenosis after PTA, especially in patients with diabetes.

PMID- 14712431
TI  - Time and exercise improve phosphate removal in hemodialysis patients.
AB  - BACKGROUND: Control of serum phosphate remains a difficult clinical issue in most
      hemodialysis (HD) patients. This study examines 2 nonpharmacological approaches
      to improving phosphate control in HD patients. METHODS: First, 9 stable HD
      patients underwent dialysis in random fashion for either 4 hours 3 times weekly
      or 5 hours 3 times weekly. Adjustments were made to blood flow rates such that
      Kt/V was the same for all sessions, thus allowing independent assessment of the
      influence of time. The primary end point was weekly dialysate phosphate removal.
      In the second study, 12 different patients underwent an exercise program in which
      they pedaled a bicycle ergometer either immediately before or during dialysis.
      Again, weekly dialysate phosphate removal was measured. RESULTS: In the time
      study, urea reduction ratio (69% +/- 0.02% versus 68% +/- 0.07, 4 versus 5 hours)
      and weekly urea removal were no different between the 2 groups. However, weekly
      phosphate removal (3,007 +/- 641 versus 3,400 +/- 647 mg; P < 0.02) significantly
      improved with longer dialysis duration. Serum phosphate levels improved, but did
      not reach statistical significance in this short-term study. In the exercise
      study, weekly phosphate removal improved with exercise, but did not reach
      significance (2,741 +/- 715 [no exercise] versus 2,917 +/- 833 [exercise
      predialysis] versus 2,992 +/- 852 mg [exercise during dialysis]; P = 0.055),
      although comparing only exercise during dialysis with no exercise reached
      significance (P = 0.02). There was no significant difference in serum phosphate
      levels. CONCLUSION: Both increased dialysis time and exercise result in increased
      dialytic removal of phosphate and could be expected in the long term to improve
      phosphate control.

PMID- 14712432
TI  - Early clinical, quality-of-life, and biochemical changes of "daily hemodialysis"
      (6 dialyses per week).
AB  - BACKGROUND: Advantages associated with an increased frequency of hemodialysis
      have been reported previously. However, previous studies were either small or not
      controlled and did not detail early clinical, biochemical, quality-of-life, urea
      kinetic, and dynamic changes when patients switched from a conventional (3
      times/wk) dialysis regimen to "daily" (6 times/wk) dialysis therapy when total
      weekly dialysis time was unchanged. METHODS: A prospective sequential study with
      21 patients as their own controls was performed. A 4-week period of conventional
      thrice-weekly dialysis (N = 240 treatments) was followed immediately by a 4-week
      period of daily (ie, 6 times/wk) dialysis (N = 480 treatments), in which each
      treatment was half the length of a conventional dialysis treatment session.
      Clinical parameters and symptoms during and between dialysis treatments were
      graded, and urea-related parameters, blood chemistry results, and nutritional
      data were determined. RESULTS: Within 4 weeks of switching to this daily dialysis
      regimen, there were improvements in blood pressure, dialysis "unphysiology,"
      intradialytic and interdialytic symptoms, and urea kinetics and dynamics. There
      were fewer machine alarms and less need for nursing interventions during
      dialysis. Nutrition and quality of life began to improve. There was no increase
      in blood access complications and no significant changes in blood chemistry
      results, hematologic parameters, or use of medications. CONCLUSION: In this short
      term study, daily dialysis appears to be a safe, better, and more physiological
      method to deliver dialysis care to patients with end-stage renal disease.

PMID- 14712433
TI  - Peritoneal dialysis catheter removal for acute peritonitis: a retrospective
      analysis of factors associated with catheter removal and prolonged postoperative
      hospitalization.
AB  - BACKGROUND: Most patients with acute peritoneal dialysis (PD) peritonitis respond
      to antibiotic therapy, but a significant minority of patients require surgical
      catheter removal to eradicate the infection. These patients may experience an
      adverse postsurgical course. METHODS: We retrospectively analyzed 64 episodes of
      acute peritonitis requiring PD catheter removal in comparison to 426 episodes
      treated with antibiotics alone. RESULTS: There were no differences between
      patients who required PD catheter removal and medically treated patients in sex
      (62% versus 60% men; P > 0.05), PD modality (31% versus 27% automated PD; P >
      0.05), time spent on PD therapy (35 versus 26 months; P > 0.05), or cause of end
      stage renal failure. Catheter removal was more likely to occur in elderly (mean
      age, 61 versus 54 years; P = 0.023) and South Asian patients (38% versus 22%; P =
      0.020) and after peritonitis caused by Escherichia coli (16% versus 4%; P =
      0.0005), Enterobacter species (5% versus 0.7%; P = 0.031), and Pseudomonas
      species (5% versus 0.7%; P = 0.031). The most significant correlation with
      requirement for surgical catheter removal was duration of peritonitis (mean, 7.5
      versus 2.8 days; P = 1.3 x 10(-6)). Fifty-three percent of catheter removals
      resulted in postoperative hospitalization longer than 10 days. Delayed discharges
      were caused by multiple reasons. Compared with discharges within 10 days,
      prolonged hospitalization was associated with increased age (mean, 64 versus 58
      years; P = 0.028) and delay in time to catheter removal (mean, 7.9 versus 5.3
      days; P = 0.027). After catheter removal, only 4% of patients successfully
      returned to maintenance PD therapy. CONCLUSION: Increased age and duration of
      peritonitis are associated with both requirement for PD catheter removal and
      prolonged postoperative hospitalization.

PMID- 14712434
TI  - Measured and estimated GFR in healthy potential kidney donors.
AB  - BACKGROUND: Nonradiolabeled iothalamate clearance is an accurate way to determine
      glomerular filtration rate (GFR). Objectives of this study are to define the
      normal range of nonradiolabeled iothalamate clearance in potential kidney donors
      and assess whether creatinine-based GFR estimates are accurate in this
      population. METHODS: Medical records of 365 potential kidney donors were
      reviewed. GFR was measured using clearance of nonradiolabeled iothalamate. Linear
      regression analysis was used to determine age- and sex-specific normal range
      values for GFR and serum creatinine. The abbreviated Modification of Diet in
      Renal Disease (MDRD) and Cockcroft-Gault prediction equations were used to
      estimate GFR from serum creatinine levels. RESULTS: GFR declined significantly
      with increasing age (P < 0.001) and was lower in women than men (P < 0.001). Men
      at the age of 20 years had an estimated mean GFR of 129 mL/min that declined by
      4.6 mL/min/decade. Women at the age of 20 years had a mean GFR of 123 mL/min that
      declined by 7.1 mL/min/decade. Regression analysis of GFR normalized to body
      surface area (nGFR) was significant for age (P < 0.001), but not sex (P = 0.826).
      A 20-year-old had a mean nGFR of 111 mL/min/1.73 m2 that declined by 4.9
      mL/min/1.73 m2/decade. Correlation between measured nGFR and estimated GFR was
      weak (r = 0.26 for abbreviated MDRD equation; r = 0.35 for Cockcroft-Gault
      equation). CONCLUSION: This study of nonradiolabeled iothalamate clearance for
      the measurement of GFR in potential kidney donors established age-adjusted normal
      values. In healthy individuals, GFR cannot be estimated accurately using the
      abbreviated MDRD or Cockcroft-Gault prediction equations.

PMID- 14712435
TI  - Early renal insufficiency and late venous thromboembolism after renal
      transplantation in the United States.
AB  - BACKGROUND: Pulmonary embolism (PE) is the most common preventable cause of death
      in hospitalized patients. Patients with severe chronic kidney disease (CKD) may
      be at increased risk for PE in comparison to the general population. Whether
      severe CKD is associated with increased risk for late venous thromboembolism
      (VTE) in a population of renal transplant recipients has not been determined.
      METHODS: Using the US Renal Data System database, we studied 28,924 patients
      receiving a kidney transplant from January 1, 1996, to July 31, 2000, with
      Medicare as primary payer, followed up until December 31, 2000. Cox proportional
      hazards regression models were used to calculate the association of transplant
      recipient estimated glomerular filtration rate (eGFR; by the Modification of Diet
      in Renal Disease formula) less than 30 mL/min/1.73 m2 (versus >30 mL/min/1.73 m2)
      1 year after renal transplantation with Medicare claims for VTE (either deep
      venous thrombosis or PE/infarction) 1.5 to 3 years after renal transplantation.
      RESULTS: The rate of VTE occurring 1.5 to 3 years after transplantation was 2.9
      episodes/1,000 person-years. eGFR less than 30 mL/min/1.73 m2 versus higher at
      the end of the first year after renal transplantation was associated with
      significantly increased risk for later VTE (adjusted hazard ratio, 2.05; 95%
      confidence interval, 1.08 to 3.89). CONCLUSION: Patients with severe CKD after
      renal transplantation should be regarded as high risk for late VTE, which is a
      potentially preventable cause of death in this population.

PMID- 14712436
TI  - The impact of hepatitis C virus viremia on renal graft and patient survival: a 9
      year prospective study.
AB  - BACKGROUND: The impact of hepatitis C virus (HCV) infection on long-term patient
      and renal graft survival is controversial. METHODS: We prospectively followed up
      for approximately 9 years 133 hepatitis B surface antigen (HBsAg)-negative
      successive renal transplant recipients for whom HCV RNA polymerase chain reaction
      (PCR) results were available before transplantation. We compared graft and
      patient survival rates and causes of death and graft failure in PCR-positive and
      PCR-negative transplant recipients. Cox proportional hazards models were used to
      detect the impact of HCV infection on patient and graft survival. We also studied
      posttransplantation hepatic function and graft performance. RESULTS: HCV RNA was
      detected in sera of 87 patients (65%). Univariate and multivariate analyses did
      not show an increased risk for death or graft failure in viremic compared with
      nonviremic transplant recipients. However, HCV-infected transplant recipients
      with chronic alanine aminotransferase level elevations had increased risks for
      death (odds ratio, 3.7; 95% confidence interval [CI], 1 to 13.7) and graft
      failure (odds ratio, 3; 95% CI, 1.4 to 6.7) compared with viremic transplant
      recipients with persistently normal liver function test results and noninfected
      patients. Five viremic and no nonviremic transplant recipients died of liver
      disease. HCV viremic transplant recipients had significantly greater frequencies
      of biochemical chronic liver disease, proteinuria, and biopsy-proven chronic
      allograft nephropathy (CAN) compared with noninfected transplant recipients.
      CONCLUSION: HCV infection per se has no adverse effect on long-term renal graft
      and patient survival. However, HCV-infected transplant recipients with abnormal
      liver function have inferior survival rates. HCV infection in renal transplants
      is associated with greater rates of proteinuria and CAN.

PMID- 14712437
TI  - Ribavirin pharmacokinetics in renal and liver transplant patients: evidence that
      it depends on renal function.
AB  - BACKGROUND: Ribavirin is approved for the treatment of chronic hepatitis C virus
      (HCV) infection. However, no recommendation exists for dosing patients with
      impaired renal function. METHODS: The authors performed a pharmacokinetic study
      in 21 HCV-positive renal or liver transplant patients. The mean creatinine
      clearance (ClCr) calculated by the Cockcroft-Gault equation was 57 mL/min (0.95
      mL/s; range, 17 to 89 mL/min [0.28 to 1.48 mL/s]). Twelve blood samples were
      obtained during a 96-hour period after the first single administration of 1,000
      mg of ribavirin. After the first pharmacokinetics (PK) and the pharmacodynamics
      (PD) profile was completed, the patients received ribavirin at 1,000 mg/d with or
      without interferon-alpha. A blood sample was taken monthly just before the oral
      administration of ribavirin. Plasma ribavirin concentrations were determined by
      high-performance liquid chromatography. RESULTS: A total of 428 plasma
      concentrations were analyzed by a population pharmacokinetic method using the
      NONlinear Mixed Effect Model program. The mean observed ribavirin apparent
      clearance (CL/F) was 9.1 L/h (with an interindividual variability of 39%). The
      influences of the age, sex, body weight (BW), serum creatinine (Scr), ClCr,
      hemoglobin, and graft status on CL/F were examined. CL/F was highly correlated
      with ClCr (r = 0.63, P < 0.01). The final regression formula was CL/F (L/h) =
      32.3 x BW x (1 - 0.0094 x age) x (1 - 0.42 x sex)/Scr, where sex = 0 for men and
      1 for women; Scr is in micromoles per liter. Sex had a larger influence on CL/F
      than that corresponding to the Cockcroft-Gault equation (ie, 15%). CONCLUSION:
      The authors present the parameters that determine ribavirin clearance in HCV+
      transplant patients with normal or impaired renal function. Moreover, we suggest
      ribavirin daily doses according to various levels of renal function.

PMID- 14712438
TI  - Long-term outcome of renal transplantation in light-chain deposition disease.
AB  - BACKGROUND: Light-chain deposition disease (LCDD) is a monoclonal gammopathy
      characterized by nonamyloid deposition of light chain in various organs. A small
      number of kidney transplantations have been performed on LCDD patients in whom
      end-stage renal disease (ESRD) developed. METHODS: The authors retrospectively
      reviewed the clinical and histologic findings and outcome of 7 patients with LCDD
      who underwent kidney transplantation at our institution. RESULTS: Renal
      insufficiency, hypertension, and proteinuria were present in all 7 patients.
      Proteinuria level was greater than 3.5 g/24 h in 3 patients. Three patients had
      microscopic hematuria. Monoclonal protein was detected in the serum in 3
      patients, urine in 5, and was undetectable in 2. Median age at presentation was
      42.7 (range, 33 to 58) years. The most common renal biopsy findings were
      mesangial expansion, mesangial nodules, tubular basement membrane thickening, and
      tubular atrophy. Kappa light chain was detected in all 7 renal biopsy results.
      Five patients were on dialysis before transplantation. LCDD recurred after a
      median of 33.3 (range, 2 to 45) months in 5 of the 7 patients. One patient
      remains on dialysis, whereas the other 4 have died. One patient died of
      progression of multiple myeloma 3 months after kidney transplantation without
      evidence of recurrence. Only 1 patient remains recurrence free after 13 years
      with normal renal allograft function. CONCLUSION: Although long-term benefits are
      occasionally seen, renal allograft survival is reduced significantly in LCDD
      patients. Kidney transplantation should not be an option for LCDD patients unless
      measures have been taken to reduce light chain production.

PMID- 14712439
TI  - Advanced glycation end products and oxidative stress are increased in chronic
      allograft nephropathy.
AB  - BACKGROUND: The histologic picture of chronic allograft nephropathy (CAN)
      resembles early arteriosclerotic lesion. Oxidative stress and advanced glycation
      end products (AGES) have been implicated in the pathogenesis of atherosclerosis
      and progression of renal disease. METHODS: The authors serially measured the
      plasma malonyldialdehyde (MDA), carbonyl protein (CP), pentosidine, and
      argpyramidine levels in 11 postrenal transplant patients with normal renal
      function (KPT) and 10 patients with biopsy proven CAN at 1, 3, 6, 9 through 12,
      and 18 through 24 months posttransplant. Data were also obtained in 16 controls
      and 13 patients with chronic renal failure (CRF). RESULTS: Although serum
      creatinine, MDA, CP, pentosidine, and argpyrimidine levels decreased during
      follow-up in KPT, it progressively increased in patients with CAN. The mean serum
      creatinine level was higher in patients with CRF (3.3 +/- 0.8 mg/dL [291.7 +/-
      70.7 micromol/L]) and CAN (2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 micromol/L]) than in
      controls (1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 micromol/L]) and KPT patients (1.2 +/
      0.2 mg/dL [109.7 +/- 17.7 micromol/L]; P < 0.001). Markers of oxidative stress
      and AGEs measured at 18 to 24 months posttransplant in patients with CAN were
      higher than in KPT, controls, and CRF patients. MDA (nmol/mL) was significantly
      higher in patients with CAN (1.30 +/- 0.30) compared with controls (0.53 +/-
      0.12), KPT (0.52 +/- 0.15), and CRF (0.74 +/- 0.27) groups (P < 0.001). Plasma CP
      (nmol/mg protein) in patients with CAN (4.3 +/- 1.00) was higher than in controls
      (1.90 +/- 0.69) and KPT (2.62 +/- 1.00) groups at the same time-point (P <
      0.001), but comparable with CRF (2.69 +/- 1.20). Plasma pentosidine
      (pmol/micromol protein) level in patients with CAN (19.69 +/- 5.05) was higher
      compared with controls (2.49 +/- 0.86), CRF (13.10 +/- 3.68), and KPT (14.32 +/-
      6.28) groups (P < 0.001). Plasma argpyrimidine (pmol/10 micromol protein) was
      higher in patients with CAN (123.8 +/- 17.9) compared with controls (4.81 +/-
      1.91), CRF (56.92 +/- 29.67), and KPT (31.1 +/- 11.1; P < 0.001) groups.
      CONCLUSION: Oxidative stress and AGEs are increased in patients with CAN, which
      cannot be explained by the decline in renal function alone. Oxidative stress and
      AGEs may be one among the nonimmune mediators of CAN.

PMID- 14712440
TI  - Thoracoscopic renal denervation for intractable autosomal dominant polycystic
      kidney disease-related pain.
AB  - The authors report a case of intractable autosomal dominant polycystic kidney
      disease-related pain associated with normal renal function, treated with renal
      denervation. Renal denervation was performed via a thoracoscopic approach. The
      good medium-term result suggests that thoracoscopic sympatho-splanchnicectomy
      would be an attractive procedure for pain management in autosomal polycystic
      kidney disease.

PMID- 14712441
TI  - Fabry disease: renal involvement limited to podocyte pathology and proteinuria in
      a septuagenarian cardiac variant. Pathologic and therapeutic implications.
AB  - In men with classical Fabry disease (alpha-galactosidase A [alpha-Gal A]
      deficiency), kidney failure occurs as early as the second decade of life. In
      contrast, men with the mild "cardiac variant" have late-onset cardiac involvement
      and proteinuria but usually do not have renal failure. To investigate the nature
      of renal involvement in the cardiac variant of Fabry disease, the renal function
      and morphology were assessed in a 75-year-old affected man. He had mild
      congestive heart failure, a reduced left ventricular ejection fraction, and
      hypercholesterolemia but lacked the classical Fabry disease manifestations,
      including angiokeratoma, acroparesthesias, corneal and lenticular opacities, and
      hypohidrosis. At age 75 years, he had significant proteinuria, and mildly
      decreased renal function (serum creatinine, 1.8 mg/dL [159 micromol/L]),
      presumably secondary to hypertensive arteriosclerosis. He had about 4% residual
      alpha-Gal A activity in leukocytes, and mutation analysis identified the N215S
      missense mutation, the common lesion in cardiac variants. Histologic and
      ultrastructural studies of kidney tissue showed that lysosomal glycosphingolipid
      deposition was extensive in podocytes, rare in tubular epithelial cells, and
      absent in mesangial, interstitial, and vascular endothelial and smooth muscle
      cells. This cardiac variant serves as an "experiment of nature" showing that the
      residual alpha-Gal A activity precludes glycosphingolipid deposition in the renal
      endothelial and other cells that lead to early renal failure in classically
      affected men, whereas marked podocyte accumulation is associated with proteinuria
      and possibly late-onset renal dysfunction. These findings have important
      implications for the renal effectiveness of enzyme replacement therapy in
      classically affected patients and for the aggressive treatment of proteinuria in
      Fabry disease.

PMID- 14712442
TI  - Palliative care.

PMID- 14712456
TI  - Prolonged postpartum proteinuria after early preeclampsia.

PMID- 14712464
TI  - Quiz page. von Hippel-Lindau disease.

PMID- 14712466
TI  - Multicentric Castleman's disease associated with glomerular microangiopathy and
      MPGN-like lesion: does vascular endothelial cell-derived growth factor play
      causative or protective roles in renal injury?
AB  - A 52-year-old Japanese man presented with fever spikes, generalized fatigue,
      anorexia, and anasarca. The patient was referred for the evaluation of fever of
      unknown origin in association with swelling of cervical, axillary, and inguinal
      lymph nodes. He also manifested nephrotic syndrome, acute renal failure,
      hepatosplenomegaly, massive pleural effusion, ascites, disseminated intravascular
      coagulation, and hypergammaglobulinemia. C-reactive protein was positive and
      plasma vascular endothelial cell-derived growth factor (VEGF) and serum
      interleukin-6 levels were markedly elevated. Lymph node biopsy results showed
      that findings were compatible with Castleman's disease of hyaline vascular type
      associated with interfollicular plasmacytosis. In conjunction with the clinical
      findings, a diagnosis of multicentric Castleman's disease was made. The patient
      underwent renal biopsy because of nephrotic syndrome, and the results showed
      proliferation of mesangial cells, lobulation of glomeruli, and tram track pattern
      of the capillary wall without immune complex deposition. Electron microscopy
      showed widening of the subendothelial space. No electron-dense deposits were
      present in both mesangial and subendothelial regions. Pathologic features were
      compatible with glomerular microangiopathy and membranoproliferative
      glomerulonephritis-like lesions. With corticosteroid therapy, systemic symptoms
      disappeared; both VEGF and interleukin-6 levels were normalized, and he went into
      complete remission of nephrotic syndrome. In this article, the role VEGF plays in
      the pathogenesis of nephrotic syndrome and glomerular microangiopathy is
      discussed.

PMID- 14712467
TI  - Immunoglobulin gamma3-heavy-chain deposition disease: report of a case and
      relationship with hypocomplementemia.
AB  - The authors describe a 54-year-old woman presenting with proteinuria, hematuria,
      and hypocomplementemia whose renal biopsy results showed diffuse increase in
      mesangial matrix and nodular formations in several glomeruli with the deposition
      of immunoglobulin gamma3-heavy-chain and complement components C1q and C3 in the
      glomeruli and on the tubular basement membranes, without associated light-chain
      deposits. Staining for the constant domains of gamma-heavy-chain showed a
      deletion of the first constant domain (CH1). These findings were consistent with
      those of gamma-heavy-chain deposition disease (gamma-HCDD). The patient was
      treated monthly with melphalan and prednisolone although a bone marrow aspirate
      did not show findings suggestive of plasmacytoma. Six courses of melphalan and
      prednisolone therapy resulted in a marked reduction of urinary protein excretion
      and marked rise of complement levels. The current case is the fourth HCDD patient
      reported featuring gamma3-heavy-chain deposition who showed severe
      hypocomplementemia and responded to chemotherapy with improved renal parameters
      and complement levels. A review of previously reported cases of HCDD showed that
      some but not all HCDD cases were associated with hypocomplementemia. The authors
      also discuss here the relationship of HCDD to hypocomplementemia.

PMID- 14712468
TI  - Stereoselectivity in the placental transfer and kinetic disposition of racemic
      bupivacaine administered to parturients with or without a vasoconstrictor.
AB  - The aim of the present study was to investigate the stereoselectivity in the
      kinetic disposition and the transplacental distribution of bupivacaine in term
      parturients during labor. Maternal age ranged from 18-37 years and fetal
      gestational age from 37.6-41.5 weeks. Healthy parturients (n = 23) received
      epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine
      (group B). Maternal venous blood was sampled at regular intervals until 8 h after
      drug administration and umbilical venous blood was obtained at delivery.
      Bupivacaine enantiomers were determined in plasma samples by HPLC using a
      Chiralcel(R) OD-R column and a UV detector. One- or two-compartment models were
      fitted to data and differences between the (+)-(R) and (-)-(S) enantiomers were
      compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine
      was evaluated using the unpaired Mann-Whitney test (P< 0.05). The disposition of
      bupivacaine in maternal plasma was stereoselective, with higher V(d/f) (140.60
      vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and C(l/f) (29.00
      vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower
      t(1/2)beta (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being
      observed for (+)-(R)-bupivacaine. The combined administration of epinephrine
      resulted in higher V(d/f) (197.86 vs. 140.60 L for (+)-(R) and 169.46 vs. 132.81
      L for (-)-(S)) and t(1/2)beta values (4.36 vs. 3.24 h for (+)-(R) and 4.45 vs.
      3.30 h for (-)-(S)). The transplacental distribution of bupivacaine was
      stereoselective only when bupivacaine was administered without epinephrine (group
      B), with a higher cord blood/maternal blood ratio being observed for (-)-(S)
      bupivacaine (0.40 vs. 0.35). Chirality 16:65-71, 2004.

PMID- 14712469
TI  - Stereospecific synthesis of "para-hydroxymexiletine" and sodium channel blocking
      activity evaluation.
AB  - Both enantiomers of "para-hydroxymexiletine" (PHM), one of the main metabolites
      of mexiletine, were synthesized and fully characterized. Properties of (R)- and
      (S)-PHM, in terms of blocking potency and stereoselectivity on frog skeletal
      muscle Na(+) channels, were evaluated. The presence of a hydroxy group on the
      aryloxy moiety in the 4-position, as in PHM, reduced potency with respect to
      mexiletine in reducing I(Na max). However, PHM showed clear use-dependent
      behavior similar to that of mexiletine and, in contrast with what is observed
      with the parent compound, maintained its stereoselectivity during the use
      dependent block. Chirality 16:72-78, 2004.

PMID- 14712470
TI  - Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole:
      Testosterone and methadone as substrates.
AB  - Racemic ketoconazole (KTZ) was the first orally active azole antifungal agent
      used in clinical practice and has become widely used in the treatment of mucosal
      fungal infections associated with AIDS immunosuppression and cancer chemotherapy.
      However, the use of KTZ has been limited because of adverse drug-drug
      interactions. KTZ blocks ergosterol biosynthesis by inhibiting the fungal
      cytochrome P450 (CYP51). KTZ is also a potent inhibitor of human cytochrome P450
      3A4 (CYP3A4) enzyme, the major drug-metabolizing CYP isozyme in the human liver.
      We examined the enantioselective differences of KTZ in the inhibition of human
      CYP3A4 and in antifungal action. Dextro- and levo-KTZ exhibited modest
      enantioselective differences with respect to CYP3A4 inhibition of testosterone
      and methadone metabolism. For both substrates levo-KTZ was approximately a 2-fold
      more potent inhibitor. We examined the enantioselective differences in the in
      vitro activity of KTZ against medically relevant species of Candida and
      Aspergillus, as well as Cryptococcus neoformans. Overall, levo-KTZ was 2-4-fold
      more active than dextro-KTZ. Therefore, levo-KTZ is a more potent inhibitor of
      CYP3A4 and has stronger in vitro antifungal activity. Chirality 16:79-85, 2004.

PMID- 14712471
TI  - Enantioselective reactions of alpha-lithiated allyl aryl sulfides using chiral
      bis(oxazoline)s.
AB  - The reaction of alpha-lithio allyl aryl sulfides, generated by treatment with n
      BuLi and chiral ligands at -78 degrees C, with ketones was examined. The alpha
      addition products were formed in preference to the gamma-addition products. The
      enantioselectivity of the alpha-addition products varied depending on the chiral
      ligand, and bis(oxazoline)-(t)Bu showed the highest enantioselectivity. Chirality
      16:86-89, 2004.

PMID- 14712472
TI  - NMR studies of chiral recognition by cyclodextrins.
AB  - Chiral recognition by cyclodextrins is of considerable importance, especially for
      pharmaceutical industry, in view of the possible side effects of the second
      enantiometer of chiral drugs. In general, it manifests itself in all NMR
      parameters (chemical shifts, coupling constants, NOE and ROE effects, and
      relaxation rates) on one hand. On the other hand, it allows one to determine the
      thermodynamic parameters characterizing diastereomeric complexes formed by
      cyclodextrins with enantiomeric guests. After an introduction and a general
      discussion of NMR manifestations of chiral recognition by cyclodextrin, the
      existing literature data on this problem will be discussed herein. Chirality
      16:90-105, 2004.

PMID- 14712473
TI  - Allylation and propargylation of chiral cyanopropanoates: an efficient route to
      long chain alpha-substituted alpha-methyl alpha-amino acids.
AB  - alpha-Methyllysine and 2-amino-2-methylundecanoic acid, two alpha,alpha
      disubstituted unnatural glycines, were synthesized using highly
      diastereoselective allylation or propargylation of chiral (1S,2R,4R)-10
      dicyclohexylsulfamoylisobornyl 2-cyanopropanoate as the key step to introduce the
      long side chain. Chirality 16:106-111, 2004.

PMID- 14712474
TI  - Pharmacokinetics of the enantiomers of trans-tramadol and its active metabolite,
      trans-O-demethyltramadol, in healthy male and female chinese volunteers.
AB  - By using a high-performance capillary electrophoresis method, the
      pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active
      metabolite, trans-O-demethyltramadol (M1), was studied in healthy male and female
      Chinese volunteers after oral administration of 100 mg trans-T hydrochloride. The
      values of Cmax for the enantiomers of trans-T and M1, and AUC0- infinity for (-)
      trans T, (+)-M1, and (-)-M1 were higher in females than in males. The values of
      V(d)/F for the enantiomers of trans-T and CLr for (+)-M1 were lower in females
      than in males. The value of t(1/2) for (-)-M1 was longer in females than in
      males. There were significant differences in pharmacokinetic parameters of the
      two enantiomers of trans-T or M1 both in males and in females. The (+)/(-)
      enantiomeric ratios of t(max), V(d)/F for trans-T in males were significantly
      different from those in females and the (+)/(-)-enantiomeric ratios of
      pharmacokinetic parameters for M1 in males were similar to those in females.
      There are gender-related differences in the pharmacokinetics of the enantiomers
      of trans-T and M1 which may be due to the greater body weights for men and/or the
      higher CYP2D6 activity in women. The pharmacokinetics of trans-T and M1 is
      stereoselective in men and women. There is a gender-related difference in the
      stereoselectivity in pharmacokinetics of trans-T in human and the
      stereoselectivity in pharmacokinetics of M1 in men is similar to that in women.
      Chirality 16:112-118, 2004.

PMID- 14712475
TI  - In vitro release and stereoselective disposition of flurbiprofen loaded to
      poly(D,L-lactide- co-glycolide) nanoparticles in rats.
AB  - Flurbiprofen (FL) is a chiral 2-arylpropionate used clinically as the racemate
      (rac-FL). This study was undertaken to investigate the influence of sustained
      release formulation on the pharmacokinetics of flurbiprofen enantiomers (-) -R-FL
      and (+)-S-FL. Therefore, a stereoselective high-performance liquid
      chromatographic (HPLC) method was developed and validated for the rapid,
      quantitative determination of (-)-R-FL and (+)-S-FL in rat plasma. Flurbiprofen
      loaded poly(D,L-lactide-co-glycolide) nanoparticles (rac-FL-PLGA) were prepared
      by in emulsion-solvent evaporation technique. Optimum conditions for rac-FL-PLGA
      nanoparticle preparation were considered, and the in vitro release of rac-FL, R
      FL, and S-FL were followed up to 48 h in phosphate buffer (pH 7.4). The three
      tested formulations revealed approximately zero-order release of either (-)-R-FL
      or S-FL up to 24 h with r >/= 0.97.Surprisingly, there was no significant
      difference between t(50%) of the three formulations (21.6 +/- 1.1 h). The
      stereoselective disposition of the sustained release rac-FL deliverv system was
      investigated in rats. There was a rapid release of R-FL, S-FL, or rac-FL followed
      by a slower one and C(max) values were observed after 2.5 +/- 2.5, 8.3 +/- 3.4
      and 8.86 +/- 3.6 h of (-)-R-FL, (+)-S-FL, and rac-FL, respectively, after
      nanoparticle administration. PLGA nanoparticles increased the mean retention time
      (MRT) of S-FL by 2.7-fold, from 6.8 to 16.3 h, compared to rac-FL. Although the
      dose of rac-FL-PLGA nanoparticles was only 2.5 times higher than that of the drug
      in the suspension, the mean (+)-S-FL concentration after 12 h was 3.4 times
      higher in the case of nanoparticles than after the free form, 10.35 +/- 1.6 and
      3.04 +/- 1.1 mg/l, respectively. The area under the concentration-time curve
      (AUC) values of (+)-S-FL and rac-FL were about 2.5-fold higher after the
      nanoparticles compared to suspension, while the AUC of the (-)-R-FL was about 3.5
      times higher. This difference may indicate that the two enantiomers have
      different absorption kinetics. The present study provides evidence that the
      sorption of racemic flurbiprofen to PLGA nanoparticles was successful in
      maintaining (at least up to 12 h) elevated plasma drug concentrations of (+)-S-FL
      in rats. Chirality 16:119-125, 2004.

PMID- 14712476
TI  - 2-(2,3-Dihydro-1H-indol-3-yl)ethanol: synthesis, separation of enantiomers, and
      assignment of absolute stereochemistry by X-ray structure analysis.
AB  - The first direct resolution of racemic 2-(2,3-dihydro-lH-indol-3-yl)ethanol
      prepared by catalytic hydrogenation of 2-(lH-indol-3-yl)ethanol-has been
      accomplished by chiral simulated moving bed (SMB) chromatography. The single
      enantiomers were isolated as their dihydrogen phosphate salts. Single-crystal X
      ray analyses were successful, revealing that the (+)-enantiomer of 2-(2,3-dihydro
      lH-indol-3-yl)ethanol has the (S) configuration. Chirality 16:126-130, 2004.

PMID- 14712477
TI  - Chiral symmetry-breaking transition in growth front of crystal phase of 1,1'
      binaphthyl in its supercooled melt.
AB  - Although the theory of spontaneous chiral symmetry-breaking in open systems was
      proposed some time ago, experimental realization of this phenomenon has not been
      achieved. In this article, we note that the crystal growth front of 1,1'
      binaphthyl shows many of the characteristics of an open system in which chiral
      symmetry-breaking has occurred. We studied the temperature profiles of the
      crystallizing surface and obtained X-ray diffraction data of the crystals grown
      from the melt under controlled conditions. The data show that, under appropriate
      conditions, the observed bimodal probability distribution of enantiomeric excess
      (ee) with maxima approximately 60% is due exclusively to chiral crystals and not
      due to racemic crystals of 1,1'-binaphthyl that can also form at large
      supercooling. The mass independence of the ee shows that the growing front
      maintains a constant ee, which is a clear signature of open systems in steady
      state. Chirality 16:131-136, 2004.

PMID- 14712479
TI  - Effects of adrenomedullin on endothelial cells in the multistep process of
      angiogenesis: involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors.
AB  - Recently, we demonstrated that U87 glioblastoma xenograft tumors treated with
      anti-adrenomedullin (AM) antibody were less vascularized than control tumors,
      suggesting that AM might be involved in neovascularization and/or vessel
      stabilization. Angiogenesis, the sprouting of new capillaries from preexisting
      blood vessels, is a multistep process that involves migration and proliferation
      of endothelial cells, remodeling of the extracellular matrix and functional
      maturation of the newly assembled vessels. In our study, we analyzed the role of
      AM on human umbilical vein endothelial cell (HUVEC) phenotype related to
      different stages of angiogenesis. Here we report evidence that AM promoted HUVEC
      migration and invasion in a dose-dependent manner. The action of AM is specific
      and is mediated by the calcitonin receptor-like receptor/receptor activity
      modifying protein-2 and -3 (CRLR/RAMP2; CRLR/RAMP3) receptors. Furthermore, AM
      was able to induce HUVEC differentiation into cord-like structures on Matrigel.
      Suboptimal concentrations of vascular endothelial growth factor (VEGF) and AM
      acted synergistically to induce angiogenic-related effects on endothelial cells
      in vitro. Blocking antibodies to VEGF did not significantly inhibit AM-induced
      capillary tube formation by human endothelial cells, indicating that AM does not
      function indirectly through upregulation of VEGF. These findings suggest that the
      proangiogenic action of AM on cultured endothelial cells via CRLR/RAMP2 and
      CRLR/RAMP3 receptors may translate in vivo into enhanced neovascularization and
      therefore identify AM and its receptors acting as potential new targets for
      antiangiogenic therapies.

PMID- 14712480
TI  - Expression of sperm protein 17 (Sp17) in ovarian cancer.
AB  - Sperm protein 17 (Sp17) is an antigenic protein highly expressed in spermatozoa.
      Sp17 expression was demonstrated recently in multiple myeloma, suggesting that it
      may be a novel cancer-testis antigen. Expression of Sp17 mRNA and protein was
      examined in human ovarian tumors. Sp17 mRNA was evaluated by reverse
      transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis of
      RNA derived from epithelial ovarian tumors and normal tissues. RT-PCR analysis
      detected Sp17 transcripts in 15 of 18 (83%) primary ovarian tumors. The
      transcript was not detected in RNA derived from normal uterus or cervix, whereas
      weak expression was noted in some normal ovarian tissue samples. Northern blot
      analysis showed no detectable Sp17 mRNA expression in normal tissues, including
      normal ovary, but showed Sp17 expression in 17 of 25 ovarian tumors (68%). To
      evaluate protein expression, mouse monoclonal antibodies were produced against
      recombinant Sp17 protein and used in Western blot and immunohistochemical
      analyses of normal reproductive tissue and primary ovarian tumor samples. Sp17
      protein was detected by Western blot analysis in normal spermatozoa and in 8 of
      19 ovarian tumor samples. Immunohistochemical studies showed Sp17 expression in
      spermatozoa, ciliated cells of the female reproductive tract, and most ovarian
      tumors evaluated. Tumors showed a predominantly nuclear localization of Sp17
      expression, with some cytoplasmic staining. These results demonstrate that Sp17,
      a protein with restricted expression in somatic tissues, is expressed in ovarian
      tumors. Because Sp17 is immunogenic, it may represent a novel target for
      immunotherapeutic interventions for ovarian cancer patients.

PMID- 14712481
TI  - Guanine nucleotide depletion triggers cell cycle arrest and apoptosis in human
      neuroblastoma cell lines.
AB  - Mycophenolic acid (MPA) specifically inhibits inosine-5'-monophosphate
      dehydrogenase, the first committed step toward GMP biosynthesis. In its
      morpholinoethyl ester pro-drug form it is one of the most promising
      immunosuppressive drugs recently developed. The aim of the present study was to
      investigate the in vitro effects of MPA, at concentrations readily attainable
      during immunosuppressive therapy, on 3 human neuroblastoma cell lines (LAN5, SHEP
      and IMR32). Mycophenolic acid (0.1-10 microM) caused a decrease of intracellular
      levels of guanine nucleotides, a G(1) arrest and a time- and dose-dependent death
      by apoptosis. These effects, associated with an up-regulation of p53, p21 and
      bax, a shuttling of p53 protein into the nucleus and a down-regulation of bcl-2,
      survivin and p27 protein, were reversed by the simultaneous addition of guanine
      or guanosine and were more evident using nondialysed serum containing
      hypoxanthine. These results suggest that in neuroblastoma cell lines clinically
      attainable concentrations of mycophenolic acid deplete guanine nucleotide pools
      triggering G(1) arrest and apoptosis through p53-mediated pathways, indicating a
      potential role of its morpholinoethyl ester pro-drug in the management of
      patients with neuroectodermal tumors.

PMID- 14712482
TI  - Increased expression of c-Ski as a co-repressor in transforming growth factor
      beta signaling correlates with progression of esophageal squamous cell carcinoma.
AB  - Transforming growth factor-beta (TGF-beta) regulates cell growth inhibition, and
      inactivation of the TGF-beta signaling pathway contributes to tumor development.
      In our previous study, altered expression of TGF-beta, TGF-beta-specific
      receptors and Smad4 was shown to correlate with tumor progression in esophageal
      squamous cell carcinoma (SCC). These components, however, were maintained
      normally in some patients with esophageal SCC. In our study, the mechanism by
      which aggressive esophageal SCC maintains these components was investigated, with
      particular emphasis on the participation of c-Ski and SnoN as transcriptional co
      repressors in TGF-beta signaling. Immunohistochemistry for c-Ski and SnoN was
      carried out on surgical specimens obtained from 80 patients with esophageal SCC.
      The expression of c-Ski and SnoN was also studied in 6 established cell lines
      derived from esophageal SCC and compared to an immortalized human esophageal cell
      line by Western blotting. High levels of expression of c-Ski, detected
      immunohistologically, were found to correlate with depth of invasion (p = 0.0080)
      and pathologic stage (p = 0.0447). There was, however, no significant correlation
      between expression of SnoN and clinicopathologic characteristics. A significant
      correlation between c-Ski and TGF-beta expression was observed. Moreover, in
      patients with TGF-beta negative expression, the survival rates of patients with c
      Ski positive expression were significantly lower than those of patients with c
      Ski negative expression (p = 0.0486). c-Ski was expressed at a high level in 5 of
      6 cell lines derived from esophageal SCC compared to immortalized esophageal
      keratinocytes. Furthermore, the cyclin-dependent kinase (CDK) inhibitor, p21 that
      was up-regulated by TGF-beta signaling was expressed at a low level in the 5 cell
      lines. The expression of c-Ski protein as a transcriptional co-repressor in TGF
      beta signaling seems to be correlated with tumor progression of esophageal SCC.

PMID- 14712483
TI  - Significance of COX-2 expression in human renal cell carcinoma cell lines.
AB  - Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important
      role in tumorigenesis in many human cancers. Yet the relationship between COX-2
      and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to
      evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis
      of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal
      renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at
      mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were
      constructed and transferred into RCC cells. Significant suppression of cellular
      proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas
      promotion was found in SMKT-R4 sense transfectants by colony-forming assay
      despite the observation that COX-2 specific inhibitor NS398 exhibited similar
      IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense
      transfectants, significant suppression of COX-2 expression and PGE2 production
      and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense
      transfectants by Western blot, ELISA assay and FACS analysis, respectively.
      Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in
      nude mice was significantly suppressed and the survival time of these mice was
      significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS
      RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in
      vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing
      RCC, and that suppression of COX-2 expression by antisense-based strategy may
      have potential utility in treatment of COX-2-expressing RCC.

PMID- 14712484
TI  - Differential regulation of VEGF, HIF1alpha and angiopoietin-1, -2 and -4 by
      hypoxia and ionizing radiation in human glioblastoma.
AB  - We examined how ionizing radiation (IR) delivered under either severe hypoxia (<
      0.1% O2) or normoxia affects the expression of hypoxia inducible factor 1alpha
      (HIF-1alpha) and the angiogenic factors vascular endothelial growth factor (VEGF)
      and angiopoietins 1, 2 and 4 in U87 human glioblastoma cells. IR was delivered as
      single doses of 0, 2, 5, 10 and 20 Gy after 6-hr hypoxic incubation and in
      normoxic controls. Irradiation at any dose did not affect the cellular protein
      levels of any of the angiopoietins, whereas hypoxia led to increasing levels of
      both angiopoietin-4 and angiopoietin-2. Levels of angiopoietin-1 protein were
      unaltered throughout the observation period. A dose-dependent increase in levels
      of secreted VEGF in the medium occurred after IR at doses from 5-20 Gy. In
      hypoxic cells, 20 Gy IR induced an additional significant increase in VEGF
      relative to nonirradiated hypoxic control cells with elevated baseline VEGF
      levels induced by hypoxia. HIF-1alpha and glucose transporter-1 (Glut-1) were not
      correspondingly upregulated by IR. Blocking HIF-1alpha by antisense treatment
      induced a reduced baseline VEGF at normoxia, while the relative upregulation of
      VEGF by IR was unaffected. These data provide evidence that VEGF is upregulated
      by IR by mechanisms independent of HIF-1 transactivation.

PMID- 14712485
TI  - Fine mapping of chromosome 22q tumor suppressor gene candidate regions in
      astrocytoma.
AB  - Astrocytomas and glioblastomas are the most frequent primary brain tumors in
      adults. Mutations and altered expression of multiple genes have been found to
      contribute to the genesis of these tumors. However, many factors in the genesis
      of astrocytic gliomas are not resolved yet. The frequent losses on several
      chromosomes indicate the role of still unidentified tumor suppressor genes. Loss
      of heterozygosity (LOH) on 22q has been described in up to 30% of astrocytic
      tumors and may be associated with progression to anaplasia. In a first step,
      information from the nearly finished physical sequence of chromosome 22 were used
      to map LOH data from 22q deletion studies on different tumor entities to identify
      potential tumor suppressor gene candidate regions. Next, a series of 153
      astrocytic gliomas was examined with 11 polymorphic markers spanning these
      regions. Forty-nine (32%) astrocytic gliomas exhibited LOH on 22q, 17 (35%) of
      which lost heterozygosity for all markers and 32 (65%) of which carried
      interstitial or partial deletions. Two regions were identified on the physical
      DNA sequence. The centromeric region spans 3 Mb and the telomeric region 2.7 Mb.
      The reduced size of these regions now allows direct analysis of all genes
      included. We already performed mutation analysis on 4 candidate genes from these
      regions (MYO18B, DJ1042K10.2, MKL1 and EP300), but did not find any mutations in
      astrocytic tumors.

PMID- 14712486
TI  - Differential gene-expression profiling in the leukemia cell lines derived from
      indolent and aggressive phases of CD56+ T-cell large granular lymphocyte
      leukemia.
AB  - As a rule, T cell large granular lymphocyte (T-LGL) leukemia runs a chronic
      clinical course without need for therapy. Some cases, however, progress to an
      aggressive disease after the indolent clinical stage. The transformation
      mechanism into a high-grade malignancy has not been well studied. We have
      established 2 leukemia cell lines, MOTN-1 and PLT-2, derived from the same clone
      of CD56+ T-LGL leukemia in chronic and aggressive phases, respectively. The
      paired availability of such cell lines is valuable in biologic and genetic
      investigation of T-LGL leukemia. We used a microarray containing 406 cDNAs to
      elucidate alterations of gene expression between the 2 cell lines. We found a
      number of genes that were differentially expressed: 13 genes with increased
      expression and 3 genes with reduced expression in PLT-2 cells as compared to MOTN
      1 cells. Increased expression of the dek, rac, Op18, CD6, CD58, CD106, Id2, ATF4,
      IRF5, ELL2 and D6 genes, and reduced expression of the GzmA and GzmK genes were
      confirmed by real-time quantitative reverse transcription-PCR, whose results
      paralleled the microarray data. These upregulated genes encode oncoproteins, cell
      surface antigens including molecules related to T cell proliferation,
      transcription factors, and a chemokine receptor. The two downregulated genes
      encode granzymes that play an important role for induction of cell death. These
      findings suggest that there is differential gene expression in different clinical
      phases of T-LGL leukemia and these differentially expressed genes would be
      potential targets for further studies to identify the genes involved in the
      transformation process of T-LGL leukemia.

PMID- 14712487
TI  - Heterozygote deficiency in thymidylate synthase enhancer region polymorphism
      genotype distribution in Hungarian colorectal cancer patients.
AB  - Thymidylate synthase (TS) gene polymorphisms are important as prognostic factors
      in cancer chemotherapy, but recent results describe that the TS enhancer region
      (TSER) polymorphic genotypes may also modulate risk for malignancies. Two
      functionally important and ethnically diverse polymorphisms are present on the TS
      transcript, TSER, a repeat polymorphism (2 or 3 repeats; 2R, 3R) affecting TS
      expression, and a 6 bp ins/del polymorphism on the 3' UTR (position TS1494, del6
      or ins6), which may influence mRNA stability. Hungarian population has one of the
      highest colorectal cancer (CRC) mortality rates in Europe, and several elevated
      dietary risk factors affect a large part of the population. In our study (99
      primary CRC cases), population analysis of the patient group genotype frequencies
      revealed a departure from the Hardy-Weinberg equilibrium and significant
      heterozygote deficiency (p < 0.05) at the TSER locus. Despite the strong linkage
      between the 2 polymorphic loci, case TS1494del genotype frequencies were normally
      distributed, as well as the genotype frequencies of the healthy control
      population (n = 102), at both loci. Case-control comparison demonstrated a lower
      relative risk of TSER heterozygotes (OR = 0.47; CI = 0.27-0.83; p = 0.008) and a
      possible higher prevalence of the 3R3R&ins6/del6 in the CRC group. The
      observation that heterozygotes are those less susceptible for CRC in the
      Hungarian population may support the possibility of 2 different pathways in which
      TS may play a role in colorectal carcinogenesis, probably nutrient (or folate)
      dependently. The lack of similar genotype effect seen with TS1494del polymorphism
      and the increased presence of one genotype combination (3R3R&ins6/del6) in the
      patient group suggest a possible TS haplotype effect influencing CRC risk.

PMID- 14712488
TI  - Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with
      high grade vulvar intraepithelial neoplasia.
AB  - Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has
      serious sequelae for the sufferer. Current treatments are associated with poor
      response and high relapse rates. The development of HPV-specific T cell
      immunotherapies offers a new approach to treatment. This will require a detailed
      understanding of the spectrum of T cell responses induced by HPV antigens, and
      how effectively viral antigens can be accessed by the immune system. We have
      investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses
      to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted
      populations of responder cells were screened against overlapping 30-35mer
      peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of
      IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the
      proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides
      covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity
      was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs)
      are relatively common in women with persistent VIN3. The HPV-specific CTL
      response, however, seems to be ineffective. There is some evidence that there are
      problems associated with the processing and presentation of HPV antigens by the
      infected vulvar epithelium. It will be crucial to address this in the design of
      any T cell based therapy for HPV-associated VIN and vulval cancer.

PMID- 14712489
TI  - Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA
      A*0201-restricted epitopes.
AB  - The design of a broad application tumor vaccine requires the identification of
      tumor antigens expressed in a majority of tumors of various origins. We
      questioned whether the major stress-inducible heat shock protein Hsp70 (also
      known as Hsp72), a protein frequently overexpressed in human tumors of various
      histological origins, but not in most physiological normal tissues, constitutes a
      tumor antigen. We selected the p391 and p393 peptides from the sequence of the
      human inducible Hsp70 that had a high affinity for HLA-A*0201. These peptides
      were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and
      in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine
      CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted
      manner. Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of
      an immune response in many HLA-A*0201+ breast cancer patients. Hsp70 is a tumor
      antigen and the Hsp70-derived peptides p391 and p393 could be used to raise a
      cytotoxic response against tumors of various origins.

PMID- 14712490
TI  - P16INK4a as an adjunct marker in liquid-based cervical cytology.
AB  - Cytological screening for cervical cancer is hampered by high false negative
      rates. Inter-observer reproducibility needs optimizing. The potential of
      p16(INK4a) as a biomarker for cervical lesions was examined in a study of liquid
      based cytology (LBC), HPV DNA testing by MY09/MY11 consensus PCR and type
      specific PCRs and p16(INK4a) immunocytochemistry on a series of 291 patients
      selected from routine screening. Comparison of the number of p16(INK4a)
      immunoreactive cells/1,000 cells exhibited a significantly higher mean count in
      HSIL (8.80 +/- 1.13) than other cytological groups. The mean count of LSIL (1.09
      +/- 0.18) was significantly higher than that of the negative group (0.82 +/-
      0.40). ASC-H and HSIL combined showed a significantly higher mean count (6.46 +/-
      1.17) than negative, ASC, ASC-US and LSIL. The mean count of immunoreactive
      cells/1,000 cells was significantly higher in HPV16 positive samples (3.22 +/-
      0.72) than in samples containing infections with types of unknown malignant
      potential (0.83 +/- 0.26) or HPV negative samples (1.17 +/- 0.41). The mean count
      in infections with other high-risk HPV types (2.55 +/- 0.52) was significantly
      higher than that in HPV negative samples. Receiver-operating characteristic
      curves yielded a test accuracy (area under curve) of 0.76, 0.79, 0.88 and 0.95
      for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. Thresholds for 95%
      sensitivity were at 0.005, 0.007, 0.098 and 0.445 immunopositive cells/1,000
      cells for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. The 95% specificity
      threshold for the detection of HSIL was at 1.87 immunopositive cells/1,000 cells.
      P16(INK4a) immunocytochemistry can be used as an adjunct to LBC in cervical
      screening, because it has a good diagnostic accuracy to discriminate HSIL and ASC
      H from other lesions. It could be used as a surrogate marker of high-risk HPV
      infections.

PMID- 14712491
TI  - Nadir prostate-specific antigen best predicts the progression to androgen
      independent prostate cancer.
AB  - The objective of our study was to analyze the value of prostate-specific antigen
      (PSA) levels before and after androgen suppression to predict the time to
      androgen-independent progression (AIP) in patients with advanced and metastatic
      prostate cancer. A series of 283 prostate cancer patients under androgen
      suppression as a single treatment was studied. The disease was locally advanced
      in 98 patients and metastatic in the remainder 185. AIP was defined after 2
      consecutive increases of serum PSA after the nadir value. The mean follow-up
      before AIP was 29.2 months (3-198). AIP was detected in 205 patients (72.4%). In
      152 patients (74.1%), the event was detected within 24 months, while in 53
      patients (25.9%), it was observed beyond 24 months. The multivariate analysis
      showed that the nadir PSA and the time to reach the nadir PSA were the most
      significant predictors of the time to AIP. The odds ratio of having a biochemical
      response greater than 24 months was 20 times higher in patients that achieved an
      undetectable PSA level of 0.2 ng/mL or less. Moreover in those patients whose
      nadir PSA reached beyond 12 months after androgen suppression the odds ratio was
      18 times higher. These results show that the ability to achieve an undetectable
      nadir PSA and the time to reach it are the most significant predictors of the
      time to AIP in patients with locally advanced and metastatic prostate cancer
      under androgen suppression as a single therapy.

PMID- 14712492
TI  - Frequent hypermethylation of 5' flanking region of TIMP-2 gene in cervical
      cancer.
AB  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of
      matrix metalloproteinases (MMPs). This multifunctional protein regulates
      activities of MMPs and possesses growth promoting effect in cell culture, anti
      tumoral, anti-apoptotic and anti-angiogenic effects in animal model systems in
      vivo. It has been shown that this gene is downregulated in cervical carcinomas.
      The mechanism of inhibition of TIMP-2 expression remains obscure. We have
      examined whether aberrant DNA methylation of the 5'CpG island of the TIMP-2 gene
      is involved in its inhibition during cervical carcinogenesis. Bisulfite-modified
      DNA sequencing and MSP assay showed aberrant methylation of TIMP-2 5'-CpG island
      in 17 of 36 (47%) invasive cervical carcinomas and in 2 of 3 cervical cancer cell
      lines. TIMP-2 gene was mostly unmethylated in the morphologically normal tissues
      adjacent to the tumors, whereas methylated alleles of this gene were found in 4
      samples. Each tumor and each cell line DNA was characterized by unique
      methylation pattern, however a discrete region of TIMP-2 CpG island upstream to
      the transcription start site was densely methylated in all hypermethylated DNA
      samples examined. The expression of TIMP-2 mRNA can be restored in the cell
      lines, in which this discrete region of TIMP-2 CpG island is methylated, by
      treatment with demethylating agents, 5-azacytidine and 5-aza-2'-deoxycytidine.
      Our data suggest that the aberrant methylation of TIMP-2 favors the development
      of primary cervical tumors. We describe for the first time the aberrant
      hypermethylation of TIMP-2 gene in human cancer.

PMID- 14712493
TI  - Screen-detected prostate cancer and the insulin-like growth factor axis: results
      of a population-based case-control study.
AB  - Higher circulating levels of IGF-I have been associated with increased risk of
      prostate and some other cancers. Most research on prostate cancer has been based
      on men with symptoms or identified following treatment of benign disease.
      However, increasing numbers of cancer cases are now detected in asymptomatic men
      following prostate-specific antigen (PSA) tests. We therefore used a population
      based case-finding exercise using the PSA test to examine whether associations
      between the IGF axis and cancer risk were apparent in this population. A matched
      case-control study was conducted among 7,383 men (50-70 years) receiving a PSA
      test as part of a case-finding exercise. Assays of IGF-I, IGF-II, IGFBP-2 and
      IGFBP-3 were performed on cases and 2 controls matched on age, recruitment center
      and calendar time. Analyses were based on 176 cases and 324 matched controls. The
      risk of prostate cancer increased across quartiles of IGF-I (highest vs. lowest
      quartile, OR = 2.34; 95% CI = 1.26-4.34; p(trend) = 0.02) and IGF-II (OR = 1.78;
      95% CI = 0.94-3.15; p(trend) = 0.09). Controlling for smoking history and IGFBP-3
      strengthened associations with cancer for both IGF-I (OR = 3.00; 95% CI = 1.50
      6.01; p(trend) 0.005) and IGF-II (OR = 2.02; 95% CI = 1.07-3.84; p(trend) = 0.04)
      Associations between the IGFs and cancer risk were stronger for advanced cases.
      Our findings suggest that both IGF-I and IGF-II are associated with an increased
      risk of screen-detected prostate cancer.

PMID- 14712494
TI  - Soft-tissue sarcoma and dioxin: A case-control study.
AB  - Soft-tissue sarcoma has been proposed to be a candidate for a dioxin-induced
      cancer. However, previous epidemiologic studies have suffered from poor exposure
      data and mixed exposures. We studied the association between sarcoma risk and
      individually estimated dioxin exposure in a general population exposed to
      relatively low levels of dioxin via food. A multicenter prospective case-control
      study was conducted in 4 university hospitals and 12 other hospitals in southern
      Finland. Participants included 110 patients with soft-tissue sarcoma (cases) and
      227 area- and age-matched controls. Controls were patients operated for
      appendicitis. Individual dioxin concentrations were analyzed from subcutaneous
      fat samples by gas chromatography-mass spectrometry. The average (range) dioxin
      concentration was 33.4 (4.4-145.5) ng/kg (toxic equivalencies in fat according to
      WHO). No increased risk associated with increased dioxin concentration was
      observed. In contrast, the highest risk of sarcoma was found at low levels of
      dioxin. Odds ratios for different quintiles as compared with the lowest quintile
      of dioxins (median, 11.5 ng/kg) varied from 0.43 (95% CI = 0.18-1.05) to 0.65
      (95% CI = 0.22-1.95). The result was little affected by studied confounders and
      the findings were similar for different sarcoma subtypes, age groups and study
      areas. The results imply that dioxin does not increase the risk of soft-tissue
      sarcoma at the present population levels.

PMID- 14712495
TI  - The increase of female breast cancer incidence in Japan: emergence of birth
      cohort effect.
AB  - During recent decades, breast cancer incidence has been increasing in Japan.
      According to the latest reports from several cancer registries in Japan, the
      breast has become the leading cancer site in female cancer incidence. To analyze
      the trend of breast cancer incidence in detail, we summarized female breast
      cancer incidence in Miyagi Prefecture, Japan during 1959-1997, and evaluated the
      period and cohort effect on breast cancer incidence using the age-period-cohort
      model. Age-specific and age-standardized rates have increased over successive
      calendar periods. Around 1980, an accelerated increase in these incidence rates
      took place. A full model including age, period and cohort was best fitted to the
      trend of incidence. In the model, the effects of period and cohort were
      statistically significant. The nonlinear effect for cohort indicates an
      increasing trend, beginning with the cohort in 1888-1897, and the nonlinear
      effect for period showed a clear increase in risk with calendar period.
      Furthermore, the full model including a linear component showed a steadily upward
      trend in the cohort effect. Based on our own epidemiologic studies previously
      conducted in Miyagi Prefecture, and other published reports, the cohort effect is
      likely to be related to the change in prevalence of women with risk factors such
      as low parity and insufficient breastfeeding. We believe that the emergence of
      the cohort effect is an important finding, although the period effect may also
      persist. The significant cohort effect may give a caution for continuous increase
      of breast cancer incidence in Japan.

PMID- 14712496
TI  - Exposure to cement dust, related occupational groups and laryngeal cancer risk:
      results of a population based case-control study.
AB  - A population-based case-control study was performed in the Rhein-Neckar region,
      Germany, to evaluate occupational risk factors for the development of laryngeal
      cancer ("Rhein-Neckar-Larynx Study"). Between May 1998 and December 2000, 257
      patients (236 males, 21 females), aged 37-80, with histologically confirmed
      laryngeal cancer, as well as 769 population control persons (702 males, 67
      females), were included (1:3 frequency matched by age and sex). History of
      occupational exposures, as well as other risk factors (tobacco, alcohol), was
      obtained with face-to-face interviews using a detailed standardized
      questionnaire. The complete individual work history was assessed. A detailed
      assessment of work conditions was obtained by job-specific questionnaires (JSQs)
      for selected jobs known to be associated with exposure to potential laryngeal
      carcinogens. Estimates for total exposure hours by substance were calculated
      based on JSQs. Published occupational hygiene data were used to infer
      semiquantitative scores of exposure intensity for specific job tasks. After
      adjustment for tobacco and alcohol intake, a significant elevated odds ratios
      (OR) could be demonstrated for persons that were exposed to cement during their
      work as building and construction workers. An OR of 2.42 was calculated for
      workers of the high exposed subgroup (95% confidence interval: 1.14-5.15; p <
      0.001). Smoking was the main confounding factor because the unadjusted cement OR
      of 3.20 dropped down to 2.42 after adjustment for tobacco intake. We conclude
      that there is good evidence for cement dust exposure acting as a tobacco, alcohol
      and asbestos independent risk factor for laryngeal carcinoma. Our study gives a
      base for further toxicologic investigations on this topic.

PMID- 14712497
TI  - Enhanced radiosensitization and chemosensitization in NF-kappaB-suppressed human
      oral cancer cells via the inhibition of gamma-irradiation- and 5-FU-induced
      production of IL-6 and IL-8.
AB  - We examined the mechanisms underlying the enhancement of radiosensitivity and
      chemosensitivity to gamma-irradiation (IR) and 5-Fluorouracil (5-FU) in human
      oral carcinoma cells (B88) in which NF-kappaB activity was constitutively
      suppressed. Three super-repressor form of IkappaBalpha cDNA-transfected cell
      (B88mI) clones and 1 empty vector-transfected cell clone (B88neo) have been
      established. We found that the tumor-forming ability in nude mice of B88mI clones
      was significantly lower than that of B88 or B88neo. This suppressed ability in
      tumorigenicity was attributed to the down-regulation of the expression of
      interleukin (IL)-1alpha, IL-6, IL-8, vascular endothelial growth factor (VEGF)
      and matrix metalloproteinase (MMP)-9 in B88mI cell clones as compared to that in
      B88 or B88neo. IR and 5-FU induced a much greater degree of apoptosis, as
      evidenced by flow cytometry analysis and annexin V staining, in B88mI cell clones
      than in B88 or B88neo. When tumor-bearing nude mice were treated with IR or 5-FU,
      the suppression of tumor growth was significantly augmented in B88mI cell clones
      as compared to that in B88 or B88neo. ELISA analysis indicated that although a
      remarkable increase in production of IL-6 and IL-8 was observed in B88 and B88neo
      after in vitro exposure to IR or treatment with 5-FU, radiotherapy and
      chemotherapy-induced production of these cytokines was significantly suppressed
      in B88mI cell clones. These findings suggest that production of angiogenic
      factors and growth factors in response to radiotherapy and chemotherapy is a
      principal mechanism of inducible radioresistance and chemoresistance in human
      oral cancers, and establish the inhibition of NF-kappaB as a rational approach to
      improve conventional radiotherapy and chemotherapy outcomes.

PMID- 14712498
TI  - Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody
      on breast cancer.
AB  - We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced
      differentiation and inhibited the growth of breast cancer cells. In this report,
      we examined whether D5 specifically delivered to breast cancer cells could have
      any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6
      4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody
      selected in our study had no significant effect on the in vitro or in vivo growth
      of breast cancer cells; however, it had cell-differentiating action. In vitro, D5
      Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2
      expressing cells, to compete with Her-2 antibody for surface receptor and to
      cause internalization. IMC (equivalent to 5 microg Her-2 antibody given
      intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of
      BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect
      of IMC treatment was similar to that observed in animals receiving D5
      continuously as a dietary supplement. These results show that the targeted
      delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of
      potential therapeutic value for the treatment of Her-2 positive breast cancer.

PMID- 14712499
TI  - Analysis of the level of mRNA expression of the membrane regulators of
      complement, CD59, CD55 and CD46, in breast cancer.
AB  - We have examined the relative mRNA expression of the complement (C) regulatory
      proteins CD59, CD55 and CD46 in RNA isolated from 50 primary breast cancer
      specimens using a semiquantitative RT-PCR approach. Having normalized the mRNA
      expression levels of the C regulators relative to actin, we subsequently
      correlated their expression with estrogen receptor (ER) and various clinical,
      pathologic and biochemical features of the disease. CD59 and CD46 were detected
      in all clinical biopsies, while CD55 mRNA was detected in the majority of
      samples. The comparative levels of expression between the 3 regulators analyzed,
      using Spearman rank correlation test, revealed a significant association (p =
      0.01; r = 0.36) between CD46 and CD59. CD46 exhibited the most striking pattern
      of association, with increased levels of expression being associated with ER
      positive samples and lower levels of expression associated with a loss of
      differentiation and epidermal growth factor receptor positivity. Application of
      Spearman rank correlation test revealed CD46 expression was significantly
      associated with expression of ER at the level of protein (p = 0.031; r = 0.31)
      and mRNA (p < 0.001; r = 0.52). CD46 expression also correlated with insulin-like
      growth factor receptor-positive samples using Spearman rank correlation test (p =
      0.016; r = 0.34), but negatively associated with tumor samples either exhibiting
      histologic grade 3 when compared to grades 1 or 2 or displaying elevated levels
      of inflammatory cell infiltrate. Immunohistochemical analysis of a limited series
      (n = 8) of paraffin-embedded breast cancers indicated that the level of CD46
      protein expression directly associates with that of the mRNA and, where
      prominent, is localized in the tumor epithelial cell population, including at the
      plasma membrane. These data provide new information on expression of these
      important regulators in breast cancer and suggest that CD46 should be evaluated
      as a novel prognostic indicator.

PMID- 14712500
TI  - HLA-B35-restricted immune responses against survivin in cancer patients.
AB  - Two HLA-A2 restricted epitopes have recently been identified from the broadly
      expressed tumor antigen survivin, and several vaccination trials in cancer
      patients based on these survivin-derived peptides have been initiated.
      Consequently, there is a crucial need for the identification of survivin epitopes
      restricted to other HLA-molecules in order to extend the proportion of patients
      that can enter these ongoing clinical trials. In the present study, we
      characterized 2 survivin-derived epitopes, which are restricted to HLA-B35.
      Specific T-cell reactivity against these survivin-derived epitopes was found in
      the peripheral blood from patients with different B-cell malignancies and
      melanoma. Substitution of the C-terminal anchor residue of the survivin-derived
      peptides improved the recognition by tumor-infiltrating lymphocytes from melanoma
      patients. Furthermore, we demonstrated spontaneous cytotoxic T-cell responses to
      survivin in a primary melanoma lesion. The characterization of these epitopes
      allows more patients can be included in the ongoing peptide-based survivin
      vaccination trials against cancer.

PMID- 14712501
TI  - High incidence of renal tumours in vitamins A and E synthesis workers: a new
      cause of occupational cancer?

PMID- 14712506
TI  - [Correlation between basic expression level of NMDA receptor NR1 subunit protein
      in hippocampus and learning ability in rats].
AB  - OBJECTIVE: To investigate the relationship between basic expression level of NMDA
      receptor NR1 subunit protein in hippocampus and learning ability of rats.
      METHODS: Using a novel-object recognition model and Morris water maze,the novel
      object recognition ability and spatial memory of SD rats were ranked, and grouped
      as the high (top 20 %) and the low (bottom 20%), respectively. NR1 subunit
      protein levels in hippocampus were measured by quantitative immunoblotting with
      NR1 subunit specific antibody. RESULT: The level of NR1 subunit protein in
      hippocampus in the high novel-object recognition ability group was 60% (P<0.01),
      higher than that in the low one, and in the high spatial memory group it was 45.4
      % (P<0.05), higher than that in the low one, respectively. CONCLUSION: The basic
      expression level of NR1 subunit protein in hippocampus is related to novel-object
      recognition ability and spatial memory of rats.

PMID- 14712507
TI  - [Surface expression and co-localization of NMDA receptor and AMPA receptor on
      dendritic tree of hippocampal neurons in culture].
AB  - OBJECTIVE: To investigate the developmental profiles on surface expression and co
      localization of NMDA receptor clusters and AMPA receptor clusters on dendrite in
      cultured hippocampal neurons of rats. METHODS: Green fluorescent protein tagged
      GluR2 subunit (GFP-GluR2) and FLAG tagged NR2B subunit (FLAG-NR2B) were
      transfected into cultured hippocampal neurons at 5 days in vitro (DIV5). FLAG
      NR2B containing NMDA receptor clusters and GFP-GluR2 containing AMPA receptor
      clusters expressed on membrane surface were then labeled in living neurons using
      anti  FLAG mAb/Cy3-conjugated anti-mouse antibody and anti-GFP pAb/Alex488
      conjugated anti-rabbit antibody. RESULT: The numbers of receptor cluster per 100
      microm dendrite in the neurons at DIV7 and DIV19 were 39.7+/-5.0 and 64.7+/-6.1
      (P<0.01) for NR2B-NMDAR, 59.1+/-3.3 and 99.7+/-6.4 (P<0.01) for GluR2-AMPAR, and
      29.9+/-4.5 and 37.5+/-2.5(P<0.05) for the co-localized, respectively. At DIV7 and
      DIV19, 75.4% and 57.9% NR2B-NMDAR clusters were co-localized with GluR2-AMPAR;
      and 50.6% and 37.6% GluR2-AMPAR clusters were co-localized with NR2B-NMDAR,
      respectively. CONCLUSION: The density of NR2B-NMDAR containing and GluR2-AMPAR
      containing receptor clusters increases during development of hippocampal neurons
      in culture. Although the co-localized clusters are increased as well in an unit
      length of dendrite, the extent to which the two receptor clusters are co
      localized decreases. These data imply a possible change in the partnership of
      AMPA receptor subtype and NMDA receptor subtype at newly formed synapses during
      development.

PMID- 14712508
TI  - [Surface expression of NMDA receptors composed of NR1 subunit and NR2A subunit
      mutants with partially deleted C-terminus in HEK293 cells].
AB  - OBJECTIVE: To examine the potential function of NMDA receptor NR2A subunit C
      terminus in assembling and surface expression of the receptor in HEK293 cells.
      METHODS: Five vectors GFP- NR2ADeltaC1- DeltaC5 were constructed for expressing N
      terminally GFP-tagged NR2A with C-terminal deletion at different regions by using
      conventional techniques of molecular cloning. The deleted region for NR2ADeltaC1
      Delta C5 was 897L-1017S, 1024D-1142P, 1149D-1347G, 1354S-1464V, and 897L-1464V.
      These plasmids were transfected alone or co-transfected with NR1-1a into HEK293
      cells. The surface NMDA receptors were immuno-stained using rabbit antibody
      against GFP and Cy3 conjugated secondary antibody in living cells. RESULT: The
      vectors GFP-NR2ADeltaC1-DeltaC5 were generated and all of them expressed GFP
      fluorescence in the transfected cells. Surface NMDA receptors were detected by
      immuno-labeling with anti-GFP in the cells co-transfected by NR1-1a and any one
      of GFP-NR2ADeltaC1-DeltaC5. However, no surface expression of NR2A proteins was
      found in the transfected cells with any one of these plasmids alone. CONCLUSION:
      Within the region downstream from the 897L of NR2A subunit, neither a particular
      domain directly interacted with ER retention domain in NR1-1a C1 cassette, nor
      that determining ER retention of NR2A subunit itself has been found, indicating
      that more complicated mechanisms might exist in which the subunit assembling and
      targeting to plasma membrane of NMDA receptors undergo.

PMID- 14712509
TI  - [Construction of expression vectors for C-terminally deleted NR2B subunit mutants
      and their application in the study of assembling of NMDA receptors].
AB  - OBJECTIVE: To investigate the role of NR2B subunit C-terminus in assembling and
      surface expression of NMDA receptor subtype composed of NR1-1a/NR2B subunits.
      METHODS: Eight vectors NR2BDelta1-Delta8) expressing GFP-tagged NR2B subunit
      mutants with various deletion in the carboxyl-terminal region were generated by
      conventional molecular cloning techniques. Each of these vectors was transfected
      alone, or co-transfected with NR1-1a into HEK293 cells. NR1-1a/GFP-NR2B receptors
      on membrane surface of the living transfected cells were immuno-stained using
      rabbit antibody against GFP followed by Cy3 conjugated secondary antibody.
      RESULTS: The eight vectors NR2BDelta1-Delta8 were successfully constructed. No
      surface labeling of GFP-tagged NMDA receptor was found for those transfected
      cells with NR1-1a, GFP-NR2B, and GFP-NR2BDelta1-Delta8 alone. GFP-tagged NMDA
      receptors were immuno-stained by anti-GFP for those cells co-transfected by NR1
      1a and GFP-NR2B or GFP-NR2BDelta1-Delta6, which were mutants with partially
      deleted c-terminus at different region. However, positive stained was not found
      for those cells co-transfected by NR1-1a and GFP-NR2BDelta 7 (lack of most C
      terminus and with PDZ binding motif fused with TM4) or GFP-NR2BDelta8 (lack of
      whole C-terminus). CONCLUSIONS: The formation of NR1-1a/NR2B sub-type NMDA
      receptor requires co-expression and assembling of NR1-1a and NR2B subunits.
      Shield or inhibition of ER retention motif within C1 cassette of NR1-1a subunit
      by NR2B subunit when assembling is not dependent on any particular region in NR2B
      C-terminus.

PMID- 14712510
TI  - [An improved quantitative method for evaluation of ischemic injury and
      neuroprotection in mouse brain slices].
AB  - OBJECTIVE: To establish a simpler and more accurate method for evaluating in
      vitro ischemic injury and neuroprotective effects of drugs through improving
      experimental instrument and quantitative index in mouse brain slices. METHODS: An
      incubation instrument was developed and its application tested. 2,3,5
      triphenyltetrazolium chloride (TTC) was used as a substrate to biosynthesize
      formazan standard in mouse brain slices, and formazan was isolated, purified and
      identified. Ischemic injury of mouse brain slices was induced by oxygen/glucose
      deprivation (OGD), the produced formazan from TTC in the cortex and striatum was
      measured at 490 nm spectrophotometrically. Edaravone and ONO-1078 were added into
      the incubation medium to observe their neuroprotective effects. RESULT: The
      incubation instrument worked well for incubating brain slices and obtaining
      stable results efficiently. Standard formazan was biosynthesized and purified
      with a purity of 99.3%, and showed a linear range of 0.05 - 1 mg/ml in absorbance
      at 490 nm (r=0.9997). OGD decreased formazan production in the cortex and
      striatum in a duration-dependent manner. Edaravone (0.01 to 1 micromol/L)
      recovered OGD-induced decrease of formazan production, but ONO-1078 showed no
      effect. CONCLUSION: The incubation instrument and quantitative measurement of
      formazan developed in this study are efficient,accurate and simple for evaluating
      ischemic injury and neuroprotection,which can be used in screening of
      neuroprotective drugs in vitro.

PMID- 14712511
TI  - [Macrophotographic measurement of brain surface area for evaluating brain edema
      after focal cerebral ischemia in mice].
AB  - OBJECTIVE: To establish a new macrophotographic measurement of brain surface area
      to evaluate brain edema after focal cerebral ischemia in mice. METHODS: Permanent
      focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in
      mice. The brains were removed 10,30 min,1,3,6,12 and 24 h after MCAO, and
      photographed in dorsal and lateral views by a digital camera. Then, 6 coronal
      slices of 1 mm thick were cut and photographed. Finally, the water content of
      brain tissue was measured by heating at 110 degrees C for 24 h. The left and
      right hemisphere areas of the brains and the brain slices were analyzed and
      calculated by MedBrain 2 imaging analyzer to evaluate brain edema. RESULT: The
      macrophotographic measurement showed that the ischemic hemisphere areas
      significantly increased from 1 h after focal cerebral ischmia, which was similar
      to the measurement of water content. This measurement for brain edema correlated
      well with those of water content and brain slice volume. CONCLUSION: The
      macrophotographic measurement is an objective and quantitative method for
      evaluating brain edema after focal cerebral ischemia.

PMID- 14712512
TI  - [An improved imaging analysis for quantitative measurement of brain slice
      volume].
AB  - OBJECTIVE: To improve computer-assisted imaging analysis for quantitatively
      measuring brain slice volume of rats and mice in comparison with conventional
      measuring methods,and to evaluate its usefulness in assessment of focal cerebral
      ischemia. METHODS: The accurate volumes of rat and mouse brain slices were
      measured by weight and special gravity measuring. The areas of brain slices were
      measured by imaging analysis, then the slice volumes of right and left
      hemispheres were calculated by multiplying the adjusted thickness of the slices.
      In addition, the brain slice volumes of right and left hemispheres from focal
      cerebral ischemic mice were compared to assess ischemic injury using the imaging
      analysis. RESULT: Area measurement by computer-assisted imaging analysis was
      linear with different accurate areas (r=1.000). Slice volumes measured by imaging
      analysis correlated well with the accurate volumes measured by special gravity
      method, r=0.809 (n=45, P<0.001) in rats, and r=0.844 (n=74, P<0.001) in mice. The
      brain volumes in ischemic hemispheres were larger than in non-ischemic
      hemispheres in ischemic mice. CONCLUSION: Computer-assisted imaging analysis can
      measure the brain slice volumes accurately and compare right and left hemisphere
      volumes quantitatively.

PMID- 14712514
TI  - [Sequence detection of HBV-DNA P and C region in HIV/HBV superinfection subjects
      with drug resistance to HAART].
AB  - OBJECTIVE: To further study the resistance of HBV to high activity antiretrovirus
      therapy(HAART). METHODS: HBV-DNA was quantitatively detected by real-time PCR in
      36 HIV/HBV superinfection subjects, C region and P region HBV-DNA in high copies
      HBV-DNA subjects were detected by routine PCR, PCR products were purified and
      sequenced and compared with the HBV international Genbank using BLSAT softy ware.
      RESULT: HBV-DNA was positive in 4 of 36 patients (11.1%) and another 3 had low
      copies(<10(4)copies/ml), one had a high HBV-DNA copies (10(7)copies/ml). It's HBV
      DNA C region sequence had mutation on 2 sites (nt 2412 T/C; nt 2413 T/C) and 1
      mutation P region (nt 741 A/G, also YMDD/YVDD) compared with HBV international
      Genbak reference sequence. CONCLUSION: The HBV resistance to HAART may be related
      with multiple genetic mutations in the C and P regain of HBV-DNA.

PMID- 14712513
TI  - [Protective effects and mechanisms of serial TCM "Huoxuehuayu" prescriptions on
      cerebral ischemia-reperfusion injury in rats].
AB  - OBJECTIVE: To determine effects and mechanisms of traditional Chinese medicine
      serial "Huoxuehuayu" (activating blood flow and removing blood stasis)
      prescriptions on cerebral ischemia-reperfusion injury in rats. METHODS: Focal
      cerebral ischemia was induced by 60 min of middle cerebral artery occlusion
      (MCAO) and followed by 3 d reperfusion. Drugs were orally administered 1 h before
      MCAO and 4 h after reperfusion and the following 2 d. The neurological scores
      were evaluated 3 d after reperfusion. Then the animals were sacrificed, the
      infarct volumes, right and left areas of brain section, the pathologic changes
      and the normal neurons in hippocampal CA1 and cortex were determined by using an
      image analyzer. Nitric oxide synthase (NOS), superoxide dismutase (SOD)
      activities and malondialdehyde (MDA) content in brain tissue were evaluated by
      spectrophotography. The expression of NMDA R1 subunit (NR1) and endothelial NOS
      (eNOS) was determined by immunoblotting technique. RESULT: Serial "Huoxuehuayu"
      prescriptions and nimodipine improved neuronal dysfunction, and reduced infarct
      size and brain edema. Serial Huoxuehuayu prescriptions and nimodipine reduced MDA
      content and NOS activity, and increased SOD activity. Western blotting analysis
      demonstrated induction of NR1. CONCLUSION: Serial Huoxuehuayu prescriptions have
      a protective effect on cerebral ischemia-reperfusion injury by reducing NOS
      activity, MDA content, expression of NR1 and increasing SOD activity.

PMID- 14712515
TI  - [Determination of amlodipine in CYP3A4 cDNA-expressed cells by HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the determination of amlodipine
      after metabolism by cytochrome P450 cDNA-expressed cells. METHODS: The
      determination was performed on a C(18) reversed phase column with a mobile phase
      composed of acetonitrile phosphates buffer (45:55, v/v, pH 4.5) with UV detection
      (lambda250nm). Propranolol was used as the internal standard. RESULT: The
      standard curve was linear over the concentration range of 0.2 - 30.0 microg/ml
      (r=0.9993), and the limits of determination was 20 ng/ml (S/N >or=3), the limits
      of quantity was 0.2 microg/ml (recovery 104.0%, RSD 11.4%, n=5). The recovery for
      this assay was (98.2+/-2.4)%, precision for inter-assay and intra-assay was <10 %
      and 6 %, respectively. CONCLUSION: The HPLC method established is simple,
      accurate and suitable for the determination of amlodipine in cytochrome p450 cDNA
      expressed cells.

PMID- 14712516
TI  - [NO/cGMP signal pathway involved in the disturbance of calcium homeostasis in
      vascular smooth muscle during the late phase of sepsis].
AB  - OBJECTIVE: To evaluate the alterations in calcium metabolism of the vascular
      smooth muscle of rat thoracic aorta in the late phase of sepsis and to
      investigate the involvement of nitric oxide (NO)/cyclic-GMP(cGMP) signal
      transduction pathway in the sepsis-induced vascular hyporeactivity. METHODS: Male
      Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture
      (CLP). Eighteen hours post CLP, rat aortic rings were removed for measurement of
      contractile responses to vasoconstrictors by using organ bath technique. RESULT:
      In endothelium intact aortic rings from CLP rats, concentration-contraction
      curves to phenylephrine (PE) and high KCl were significantly decreased when
      compared with those from control rats. The transient contraction induced by PE in
      calcium-free Krebs solution and the concentration-dependent contraction to
      CaCl(2)in KCl-depolarized medium were also markedly reduced. The hyporeactivity
      to vasoconstrictors was completely reversed by pretreatment either with
      aminoguanidine (AMG), a selective inducible nitric oxide synthase inhibitor, or
      with 1H [1,2,4] oxadiazolo[4,3-a] quininoxalin-1-one(ODQ), an inhibitor of NO
      sensitive guanylyl cyclase. CONCLUSION: A generalized impairment in calcium
      handling in vascular smooth muscle,including the calcium influx through the
      voltage-operated and receptor-operated channels and calcium release from
      intracellular calcium stores, is involved in vascular hyporeactivity during the
      late phase of sepsis. The NO/cGMP signal transduction pathway might be involved
      in this defect in vascular smooth muscle.

PMID- 14712517
TI  - [Suppression of nitric oxide on cytotoxicity of Lomustine in glioma cell line BT-
      325].
AB  - OBJECTIVE: To investigate the effect of nitric oxide (NO) on cytotoxicity of
      Lomustine (CCNU) in vitro. METHODS: CCNU was used to treat human glioma cell line
      BT-325 with different concentration of cytokines or NO donors, NO levels was
      measured by Griess assay and cell survival was evaluated by MTT assay. RESULT:
      (1) Pretreatment with IL-1 beta and LPS markedly suppressed CCNU cytotoxicity in
      BT-325 cells with a significant increase in NO production (P<0.05). This function
      could be inhibited by L-NAME. (2) DETA NONOate suppressed cytotoxicity of CCNU to
      BT  -325 cells in a dose-dependent manner (P<0.05). (3) CCNU co-cultured with
      SNAP for 24 h showed higher cytotoxic to BT-325 cells(P<0.05). CONCLUSION: NO
      partly suppresses cytotoxicity of Lomustine, which might be associated with
      chemoresistance of BT-325 cells against CCNU in vitro. NO can also slow the
      degradation of CCNU in water solution.

PMID- 14712518
TI  - [Effects of sodium hyaluronate on growth and adhesion of two human colorectal
      cancer cell lines in vitro].
AB  - OBJECTIVE: To investigate the effects of sodium hyaluronate on the growth and
      adhesion of colorectal cancer cells. METHODS: Human colorectal cancer cell lines
      SW620 and Colo205 were treated with sodium hyaluronate (25 -2,500 microg/ml), and
      cancer cell proliferation was measured by MTT assay in vitro. Flow-cytometric
      analysis was applied to detect expression of CD44 on SW620 and Colo205 cells.
      RESULT: In vitro sodium hyaluronate enhanced proliferation of Colo205 cells, but
      it had no appreciable effect on SW620 growth under the same doses, Meantime, CD44
      expression on cancer cells decreased compared with controls. CONCLUSION: In vitro
      sodium hyaluronate has different effects on growth of different colorectal cancer
      cell lines, but can inhibit CD44 expression of colorectal cancer cells and
      influence their ability of adhesion.

PMID- 14712519
TI  - [Detection and clinical significance of plasma urokinase-type plasminogen
      activator and its soluble receptor in patients with multiple myeloma].
AB  - OBJECTIVE: To study the plasma levels of urokinase-type plasminogen activator(u
      PA) and its soluble receptor(suPAR )in patients with multiple myeloma(MM) and to
      evaluate their clinical significance. METHODS: Plasma u-PA and suPAR levels in 34
      MM cases were measured with enzyme-  linked immunosorbent assay (ELISA). The
      changes of plasma u-PA and suPAR levels in 6 MM cases were observed in succession
      before and after chemotherapy. RESULT: The plasma u-PA and suPAR levels of MM
      patients were significantly higher than those of controls. The plasma u-PA and
      suPAR levels in the progress period was significantly higher than those in the
      stable period of MM patients as well as in controls (P<0.01), whereas there were
      no significant difference between the stable period of MM patients and controls
      (P>0.05). Among 6 cases,the plasma u-PA and suPAR levels after chemotherapy were
      significantly lower than those before chemotherapy (P<0.05). MM patients with
      tumor cells >20% in bone marrow smear had higher levels of plasma u-PA and suPAR
      than those with tumor cells <19% (P<0.05  P<0.01). The plasma u-PA and suPAR
      levels were positively correlated with the levels of serum globulin and the
      percentage of tumor cells in bone marrow,but negatively correlated with the
      levels of serum albumin. CONCLUSION: Plasma u-PA and suPAR levels can serve as an
      index for clinical staging and assessing the therapeutic effect in MM patients.

PMID- 14712520
TI  - [Plasma levels of ascorbic acid and vitamin E in patients with liver cirrhosis].
AB  - OBJECTIVE: To investigate the plasma levels of ascorbic acid and vitamin E in
      patients with liver cirrhosis and to explore their significance. METHODS: The
      plasma levels of ascorbic acid,vitamin E and lipoperoxides in patients with liver
      cirrhosis were measured, and the results were compared with those of sex-and age
      matched healthy subjects. RESULT: The plasma levels of ascorbic acid, vitamin E
      and lipoperoxides in the patients group were (42.94 +/-6.99)micromol/L, (17.99 +/
      3.51)micromol/L and (14.09 +/-1.28)micromol/L, respectively, while those in the
      control group were (53.30 +/-9.45)micromol/L (t=9.50, P=0.000), (24.59 +/
      7.22)micromol/L (t=7.94, P=0.000) and (12.11 +/-1.20)micromol/L (t=17.21,
      P=0.000), respectively. CONCLUSION: The levels of ascorbic acid and vitamin E in
      patients with liver cirrhosis decrease significantly,which may indicates the
      disturbance of balance between oxidation and antioxidation.

PMID- 14712521
TI  - [Clincal analysis of 302 patients with syphilis].

PMID- 14712522
TI  - [Transport and translocation of ricin in cells: recent discoveries].

PMID- 14712523
TI  - [Expression of vascular endothelial growth factor receptor in patients with
      psoriasis].

PMID- 14712524
TI  - What you need to know about the 2004 OIG work plan.

PMID- 14712525
TI  - Finance. A surge in bad debt.

PMID- 14712526
TI  - Technology. A giant step for the EHR.

PMID- 14712527
TI  - Patient services. Palliative providers.

PMID- 14712528
TI  - Employee satisfaction. Can we talk?

PMID- 14712529
TI  - Preparedness. Biodefense network.

PMID- 14712530
TI  - Preparedness. Disaster on-call.

PMID- 14712531
TI  - Physician shortage. Less doubt on docs.

PMID- 14712532
TI  - Restructuring. Wasteful work.

PMID- 14712533
TI  - The data page. Specialty hospitals update.

PMID- 14712534
TI  - Same ol' same ol'.

PMID- 14712535
TI  - "Can you hear me now?" Providers must give patients a voice in efforts to reduce
      medical errors.
AB  - Efforts to improve health care safety can succeed only if providers listen to and
      otherwise actively involve patients. Several hospitals have created strategies to
      educate both staff and consumers to create a true provider-patient partnership
      that reduces the chance for errors.

PMID- 14712536
TI  - The patient experience.
AB  - Measuring patient experience, rather than satisfaction, is gaining leverage with
      employers, payers and the government. We look at why it's better and how it can
      improve quality.

PMID- 14712537
TI  - Reinventing the VA. Civilian providers find valuable lessons in a once-maligned
      health care system.
AB  - Once maligned for its health care system, the Veterans Administration in recent
      years has improved the quality of the care it offers, creating a sophisticated
      electronic medical record and streamlining business processes, such as bed use
      and prescription drug procurement. Civilian hospitals should take note.

PMID- 14712538
TI  - Pressures converge in the ICU. Hospitals turn to IT and process changes to
      improve outcomes and satisfaction.
AB  - The ICU is where all the pressures of a hospital show themselves in high relief.
      Quality, work processes and staffing are more challenging here. This Clinical
      Management article examines how hospitals are reducing mortality rates,
      increasing patient and staff satisfaction, and bringing efficiencies to the ICU
      through high- and low-tech solutions.

PMID- 14712539
TI  - The nurse, M.D. and IT. Executive dialogue series.
AB  - Clinical information systems are proven to enhance workflow and outcomes, and yet
      hospitals often face staff resistance when systems are installed. This roundtable
      discussion explores how nurses and physicians can collaborate on developing IT
      systems.

PMID- 14712540
TI  - Information is power.

PMID- 14712541
TI  - The perfect mix for your portfolio.

PMID- 14712542
TI  - In praise of boundaries. A conversation with Miss Manners. Interview by Diane L.
      Coutu.
AB  - The past three decades have been a time of increasing informality in the American
      workplace. It's easy to characterize this growing comfort with the casual as a
      positive step for workplace culture, an outgrowth of the American democratic
      belief in workers' equality. Informal environments are said to be more trusting
      and open, and workers who are free to express their personalities are more
      comfortable and thus more creative--right? According to etiquette guru Judith
      Martin--known far and wide as Miss Manners--informality in the workplace may do
      more harm than good. Without some formality in social intercourse, Miss Manners
      argues, human interactions end up being governed by laws, which are too heavy
      handed to serve as a guide through the nuances of personal--or professional-
      behavior. Since our earliest beginnings, we have developed formal rules to
      accompany shared human experiences, such as eating and mourning. Yet, says Miss
      Manners, something in us rebels against form and etiquette, and every so often,
      an anti-manners movement takes hold, and people come to believe that following
      etiquette is unnatural. One recent such movement has led to the belief that a
      distinction between our work life and our professional life is unnecessary. If we
      hope to reassure our customers that we are indeed professional, however, we need
      to be aware of the boundaries of professional behavior. On the whole, Miss
      Manners argues, informality in the workplace leads to a host of problems, from
      making employees feel pressured to "socialize" with coworkers during weekends and
      evenings to sexual harassment. Despite the shortcomings of informality in the
      American workplace, though, Miss Manners believes that we have the best code of
      manners the world has ever seen-in theory. In practice, American etiquette is
      undoubtedly still a work in progress.

PMID- 14712543
TI  - The one number you need to grow.
AB  - Companies spend lots of time and money on complex tools to assess customer
      satisfaction. But they're measuring the wrong thing. The best predictor of top
      line growth can usually be captured in a single survey question: Would you
      recommend this company to a friend? This finding is based on two years of
      research in which a variety of survey questions were tested by linking the
      responses with actual customer behavior--purchasing patterns and referrals--and
      ultimately with company growth. Surprisingly, the most effective question wasn't
      about customer satisfaction or even loyalty per se. In most of the industries
      studied, the percentage of customers enthusiastic enough about a company to refer
      it to a friend or colleague directly correlated with growth rates among
      competitors. Willingness to talk up a company or product to friends, family, and
      colleagues is one of the best indicators of loyalty because of the customer's
      sacrifice in making the recommendation. When customers act as references, they do
      more than indicate they've received good economic value from a company; they put
      their own reputations on the line. And they will risk their reputations only if
      they feel intense loyalty. The findings point to a new, simpler approach to
      customer research, one directly linked to a company's results. By substituting a
      single question--blunt tool though it may appear to be--for the complex black box
      of the customer satisfaction survey, companies can actually put consumer survey
      results to use and focus employees on the task of stimulating growth.

PMID- 14712544
TI  - How (un) ethical are you?
AB  - Answer true or false: "I am an ethical manager." If you answered "true," here's
      an Uncomfortable fact: You're probably wrong. Most of us believe we can
      objectively size up a job candidate or a venture deal and reach a fair and
      rational conclusion that's in our, and our organization's, best interests. But
      more than two decades of psychological research indicates that most of us harbor
      unconscious biases that are often at odds with our consciously held beliefs. The
      flawed judgments arising from these biases are ethically problematic and
      undermine managers' fundamental work--to recruit and retain superior talent,
      boost individual and team performance, and collaborate effectively with partners.
      This article explores four related sources of unintentional unethical decision
      making. If you're surprised that a female colleague has poor people skills, you
      are displaying implicit bias--judging according to unconscious stereotypes rather
      than merit. Companies that give bonuses to employees who recommend their friends
      for open positions are encouraging ingroup bias--favoring people in their own
      circles. If you think you're better than the average worker in your company (and
      who doesn't?), you may be displaying the common tendency to overclaim credit. And
      although many conflicts of interest are overt, many more are subtle. Who knows,
      for instance, whether the promise of quick and certain payment figures into an
      attorney's recommendation to settle a winnable case rather than go to trial? How
      can you counter these biases if they're unconscious? Traditional ethics training
      is not enough. But by gathering better data, ridding the work environment of
      stereotypical cues, and broadening your mind-set when you make decisions, you can
      go a long way toward bringing your unconscious biases to light and submitting
      them to your conscious will.

PMID- 14712545
TI  - Growth outside the core.
AB  - Growth in an adjacent market is tougher than it looks; three-quarters of the
      time, the effort fails. But companies can change those odds dramatically. Results
      from a five-year study of corporate growth conducted by Bain & Company reveal
      that adjacency expansion succeeds only when built around strong core businesses
      that have the potential to become market leaders. And the best place to look for
      adjacency opportunities is inside a company's strongest customers. The study also
      found that the most successful companies were able to consistently, profitably
      outgrow their rivals by developing a formula for pushing out the boundaries of
      their core businesses in predictable, repeatable ways. Companies use their
      repeatability formulas to expand into any number of adjacencies. Some companies
      make repeated geographic moves, as Vodafone has done in expanding from one
      geographic market to another over the past 13 years, building revenues from $1
      billion in 1990 to $48 billion in 2003. Others apply a superior business model to
      new segments. Dell, for example, has repeatedly adapted its direct-to-customer
      model to new customer segments and new product categories. In other cases,
      companies develop hybrid approaches. Nike executed a series of different types of
      adjacency moves: it expanded into adjacent customer segments, introduced new
      products, developed new distribution channels, and then moved into adjacent
      geographic markets. The successful repeaters in the study had two common
      characteristics. First, they were extraordinarily disciplined, applying rigorous
      screens before they made an adjacency move. This discipline paid off in the form
      of learning curve benefits, increased speed, and lower complexity. And second, in
      almost all cases, they developed their repeatable formulas by studying their
      customers and their customers' economics very, very carefully.

PMID- 14712546
TI  - Developing your leadership pipeline.
AB  - Why do so many newly minted leaders fail so spectacularly? Part of the problem is
      that in many companies, succession planning is little more than creating a list
      of high-potential employees and the slots they might fill. It's a mechanical
      process that's too narrow and hidebound to uncover and correct skill gaps that
      can derail promising young executives. And it's completely divorced from
      organizational efforts to transform managers into leaders. Some companies,
      however, do succeed in building a steady, reliable pipeline of leadership talent
      by marrying succession planning with leadership development. Eli Lilly, Dow
      Chemical, Bank of America, and Sonoco Products have created long-term processes
      for managing the talent roster throughout their organizations--a process Conger
      and Fulmer call succession management. Drawing on the experiences of these best
      practice organizations, the authors outline five rules for establishing a healthy
      succession management system: Focus on opportunities for development, identify
      linchpin positions, make the system transparent, measure progress regularly, and
      be flexible. In Eli Lilly's "action-learning" program, high-potential employees
      are given a strategic problem to solve so they can learn something of what it
      takes to be a general manager. The company--and most other best-practice
      organizations--also relies on Web-based succession management tools to demystify
      the succession process, and it makes employees themselves responsible for
      updating the information in their personnel files. Best-practice organizations
      also track various metrics that reveal whether the right people are moving into
      the right jobs at the right time, and they assess the strengths and weaknesses
      not only of individuals but of the entire group. These companies also expect to
      be tweaking their systems continually, making them easier to use and more
      responsive to the needs of the organization.

PMID- 14712547
TI  - Kill a brand, keep a customer.
AB  - Most brands don't make much money. Year after year, businesses generate 80% to
      90% of their profits from less than 20% of their brands. Yet most companies tend
      to ignore loss-making brands, unaware of the hidden costs they incur. That's
      because executives believe it's easy to erase a brand; they have only to stop
      investing in it, they assume, and it will die a natural death. But they're wrong.
      When companies drop brands clumsily, they antagonize loyal customers: Research
      shows that seven times out of eight, when firms merge two brands, the market
      share of the new brand never reaches the combined share of the two original ones.
      It doesn't have to be that way. Smart companies use a four-step process to kill
      brands methodically. First, CEOs make the case for rationalization by getting
      groups of senior executives to conduct joint audits of the brand portfolio. These
      audits make the need to prune brands apparent throughout the organization. In the
      next stage, executives need to decide how many brands will be retained, which
      they do either by setting broad parameters that all brands must meet or by
      identifying the brands they need in order to cater to all the customer segments
      in their markets. Third, executives must dispose of the brands they've decided to
      drop, deciding in each case whether it is appropriate to merge, sell, milk, or
      just eliminate the brand outright. Finally, it's critical that executives invest
      the resources they've freed to grow the brands they've retained. Done right,
      dropping brands will result in a company poised for new growth from the source
      where it's likely to be found--its profitable brands.

PMID- 14712548
TI  - How we're fixing up Tyco.
AB  - Among all the companies that were touched by scandal in 2002, Tyco was uniquely
      positioned to serve as a laboratory for governance reform. It had solid
      manufacturing businesses and, unlike Enron or WorldCom, it was not the victim of
      massive, systemic accounting fraud. Yes, there was serious malfeasance at the top
      -exemplified by the $6,000 shower curtain, the $2,200 wastebasket, and the other
      extravagant items purchased at shareholders' expense for former CEO Dennis
      Kozlowski's New York apartment. But undergirding the company was a foundation of
      profitable basic businesses. In this article, Tyco's first-ever senior vice
      president for corporate governance describes the steps the company is taking to
      wipe the slate clean and restore share-holders' and employees' trust in its
      operations. The company began by bringing in a new CEO, Ed Breen; hiring some 60
      new senior executives; swapping out the entire board of directors with
      individuals who boast strong backgrounds in operations as well as in finance; and
      meticulously, systematically scrubbing all the books. Tyco's new board is clear
      about who has authority over which transactions and, with three executives within
      the company reporting directly to it, has a window into day-to-day affairs. Most
      important, Tyco is creating the conditions for good governance below the senior
      executive level, including a stronger boundary between finance and operations
      management. "In the heat of the new economy ... it became unfashionable for
      [finance] to exercise checks and balances on [operations]," Pillmore explains,
      which is why a lot of abuses went unchecked at many companies. After more than a
      year of effort, much of the groundwork for effective governance has been laid at
      Tyco. Now, the challenge is to get the word out about the reforms and let the
      effects speak for themselves.

PMID- 14712549
TI  - Expensing stock options: a fair-value approach.
AB  - Now that companies such as General Electric and Citigroup have accepted the
      premise that employee stock options are an expense, the debate is shifting from
      whether to report options on income statements to how to report them. The authors
      present a new accounting mechanism that maintains the rationale underlying stock
      option expensing while addressing critics' concerns about measurement error and
      the lack of reconciliation to actual experience. A procedure they call fair-value
      expensing adjusts and eventually reconciles cost estimates made at grant date
      with subsequent changes in the value of the options, and it does so in a way that
      eliminates forecasting and measurement errors over time. The method captures the
      chief characteristic of stock option compensation--that employees receive part of
      their compensation in the form of a contingent claim on the value they are
      helping to produce. The mechanism involves creating entries on both the asset and
      equity sides of the balance sheet. On the asset side, companies create a prepaid
      compensation account equal to the estimated cost of the options granted; on the
      owners'-equity side, they create a paid-in capital stock-option account for the
      same amount. The prepaid-compensation account is then expensed through the income
      statement, and the stock option account is adjusted on the balance sheet to
      reflect changes in the estimated fair value of the granted options. The
      amortization of prepaid compensation is added to the change in the option grant's
      value to provide the total reported expense of the options grant for the year. At
      the end of the vesting period, the company uses the fair value of the vested
      option to make a final adjustment on the income statement to reconcile any
      difference between that fair value and the total of the amounts already reported.

PMID- 14712550
TI  - Does kindergarten need cops? The youngest schoolkids are acting out in really
      outrageous ways. Why?

PMID- 14712551
TI  - China's secret plague.

PMID- 14712552
TI  - An easier colon test. A virtual colonoscopy is now as good as the real thing. Is
      it right for you?

PMID- 14712553
TI  - Rushing to judgment.

PMID- 14712554
TI  - Can we afford all this?

PMID- 14712555
TI  - Six questions about the new Medicare bill.

PMID- 14712556
TI  - Why so many of us are getting diabetes.

PMID- 14712557
TI  - Practice, practice. Experienced surgeons do a better job. Check on yours before
      your operation.

PMID- 14712559
TI  - Choice and accountability.

PMID- 14712560
TI  - Cost cure-all? Or unhealthy shift?

PMID- 14712561
TI  - Dancing in the dark. New hope for AIDS in Africa.

PMID- 14712562
TI  - Getting rid of extra pounds.

PMID- 14712563
TI  - Relief that may be too risky.

PMID- 14712564
TI  - Breast implants: continue to be cautious.

PMID- 14712565
TI  - Going beyond Prozac.

PMID- 14712566
TI  - How genes affect moods.

PMID- 14712567
TI  - A step past chemotherapy.

PMID- 14712569
TI  - How to halt another outbreak.

PMID- 14712568
TI  - Growing up healthy, afterward.

PMID- 14712570
TI  - When the body attacks itself.

PMID- 14712571
TI  - Next: the Polypill prescription.

PMID- 14712572
TI  - New inroads against AIDS.

PMID- 14712573
TI  - Muppets with a message of hope.

PMID- 14712574
TI  - To save the stricken brain.

PMID- 14712575
TI  - Into the darkness of the mind.

PMID- 14712576
TI  - Unraveling the secrets of the cell.

PMID- 14712577
TI  - The ED picture today.

PMID- 14712578
TI  - Emphysema and PFTs.

PMID- 14712579
TI  - Collect from patients online?

PMID- 14712580
TI  - Don't fall into these liability traps.

PMID- 14712581
TI  - Why I carry a gun.

PMID- 14712582
TI  - Don't let a soft economy slow your practice.

PMID- 14712583
TI  - Invest in a surgicenter?

PMID- 14712584
TI  - Look before you leap.

PMID- 14712585
TI  - Take the bounce out of rubber checks.

PMID- 14712586
TI  - They won't let us treat the poor.

PMID- 14712588
TI  - How to "fire" a patient.

PMID- 14712587
TI  - Is your coding on target?

PMID- 14712589
TI  - Get lawyers' promises in writing.

PMID- 14712590
TI  - Pensions cut deep. After years of reduced or eliminated pension fund
      contributions, hospitals are being forced to pay up.
AB  - When the economy was booming and investment returns were strong, many hospitals
      benefited from "funding holidays" that let them reduce or eliminate annual
      pension fund payments. But not-for-profit hospitals' pension funds lost more than
      6% last year, and a discount-rate drop boosted funding requirements. It's a
      "double whammy," according to Kim McCarthy, left, of Trinity Health.

PMID- 14712591
TI  - A new former title. Scully--regulator, cheerleader, cowboy--to quit as CMS chief
      before implementing reform bill.

PMID- 14712592
TI  - Listing their top concerns.

PMID- 14712593
TI  - Hasta la vista--for now. Will Schwarzenegger's move terminate policy plans?

PMID- 14712594
TI  - Hitting bottom. The JCAHO's profits plummet after 2 record years.

PMID- 14712595
TI  - Profits first. JCAHO execs rewarded for subsidiary's success.

PMID- 14712596
TI  - Change of heart? AMA rethinking assertion there are too many docs.

PMID- 14712597
TI  - Support for scans. Studies present strong case for CT screening.

PMID- 14712598
TI  - Governance rehab. Judge tells HealthSouth to cut board members.

PMID- 14712599
TI  - Opening the lines of communication. CDC program helps involve reporters in the
      fight to promote public health.

PMID- 14712600
TI  - Operators are owning up. While hospital management firms say they don't target
      their clients for acquisition, such deals can make sense once conflicts are
      addressed.

PMID- 14712601
TI  - Shrinking technology. Nanotechnology holds the promise of spectacular medical
      advances, including a cure for cancer, but critics warn of dire consequences.

PMID- 14712602
TI  - The heart.

PMID- 14712603
TI  - The future is now.

PMID- 14712604
TI  - A day at a time.

PMID- 14712605
TI  - Eyeing signs of trouble.

PMID- 14712606
TI  - The arsenal. The latest in drugs, surgery, and devices.

PMID- 14712607
TI  - Hidden problem. Many people don't know they're hypertensive.

PMID- 14712608
TI  - A real fear of failure.

PMID- 14712609
TI  - Hearts of steel.

PMID- 14712610
TI  - Hearts and minds.

PMID- 14712611
TI  - Got hormones?

PMID- 14712612
TI  - Blame Canada. New Hampshire will defy the FDA and buy drugs on the Net.

PMID- 14712613
TI  - Health economics in rheumatology--an international conference.

PMID- 14712614
TI  - Regulatory issues and economic efficiency.

PMID- 14712615
TI  - Cost of musculoskeletal diseases: impact of work disability and functional
      decline.
AB  - Persons with all forms of musculoskeletal conditions incur total medical care
      expenditures of about US$240 billion, or about 2.9% of GDP. Of this total,
      approximately US$77 billion, or about 0.9% of GDP, would not have occurred in the
      absence of the musculoskeletal conditions. Such persons had lower labor force
      participation rates, resulting in indirect costs of about US$98 billion; of this
      amount, almost all (over US$90 billion) remained after taking into account
      characteristics other than the presence of a musculoskeletal condition that might
      result in lower earnings. Thus, the majority of direct costs incurred by persons
      with musculoskeletal conditions would occur in the absence of the conditions, but
      the wage losses would not occur were the conditions to be eradicated. The
      importance of indirect costs in the economics of musculoskeletal conditions is
      underscored by the studies of the costs of specific diseases. In all but OA,
      indirect costs are at least as large as, if not larger than, direct costs.
      Reducing the economic impact of RA, SLE, AS, and low back pain requires
      treatments that reduce work disability associated with each of these conditions.
      Some promising results from short term studies have been reported, but it would
      appear to be an appropriate time to inaugurate trials focused on longterm work
      outcomes.

PMID- 14712616
TI  - Prioritizing investments in health: can we assess potential value for money?

PMID- 14712617
TI  - Cost-effectiveness modeling in rheumatology: toward principles of good practice.

PMID- 14712618
TI  - Knowing what you don't know: Bayesian approaches to uncertainty in economic
      evaluations.

PMID- 14712619
TI  - Towards a reference case for use in future economic evaluations of interventions
      in osteoarthritis.

PMID- 14712620
TI  - Towards a reference case for economic evaluation of osteoporosis treatments.

PMID- 14712621
TI  - Glycohemoglobin analyzers.
AB  - For the millions of people with diabetes, maintaining near-normal glucose levels
      is vital for reducing or slowing the complications of the disease. A crucial tool
      for monitoring blood glucose levels is the glycohemoglobin (GHb) test. GHb
      analysis indicates the amount of glucose a patient's red blood cells were exposed
      to during the previous two to three months, allowing physicians to track trends
      and make appropriate changes in therapy. In the United States, this test is
      commonly performed on blood samples that have been sent to a laboratory, with
      written results provided to the physician several days later. Recently, though,
      analyzers have come onto the market that can be used at the point of care--a
      clinic or physician's office--or even in the home, providing results immediately.
      We evaluated five GHb analyzers from four suppliers: Axis-Shield, Bayer, Bio-Rad
      Laboratories, and Metrika. These products vary considerably--for example, one is
      a single-use test kit intended for point-of-care settings, while another is a
      batch analyzer that can run 15 samples at a time and is designed for low- to
      moderate-volume laboratory use. Our testing focused primarily on the analyzers'
      accuracy, precision, and ease of use. Different facilities will have different
      requirements, and none of these factors alone should determine a facility's
      purchasing decision. Rather, purchasers will have to balance all the performance
      factors--along with cost--when choosing a product. Consequently, we have provided
      separate ratings for hospital laboratory testing, point-of-care testing, and--for
      the one applicable unit--home testing.

PMID- 14712622
TI  - Anesthesia carbon dioxide absorber fires.

PMID- 14712623
TI  - Hearing aids and EMI.

PMID- 14712624
TI  - Improper use of alcohol-based skin preps can cause surgical fires.

PMID- 14712625
TI  - Patient-supplied medical equipment.

PMID- 14712626
TI  - Are you ready for 2004?

PMID- 14712627
TI  - Cross-cultural competence.

PMID- 14712628
TI  - New health care regulations.

PMID- 14712629
TI  - Construction, purification, and characterization of Escherichia coli RNA
      polymerases tagged with different fluorescent proteins.

PMID- 14712630
TI  - Purification of Bacillus subtilis RNA polymerase and associated factors.

PMID- 14712631
TI  - Determination of Escherichia coli RNA polymerase structure by single particle
      cryoelectron microscopy.

PMID- 14712632
TI  - Crystallographic analysis of Thermus aquaticus RNA polymerase holoenzyme and a
      holoenzyme/promoter DNA complex.

PMID- 14712633
TI  - Purification of Rhodobacter sphaeroides RNA polymerase and its sigma factors.
AB  - This article summarized methods to obtain RNA polymerase and sigma factors that
      can be used to analyze the in vitro control of gene expression by the facultative
      phototroph R. sphaeroides. While not a topic of this article, these purified
      components also allow one to analyze R. sphaeroides promoters that use activators
      to stimulate transcription. We expect that these approaches will be increasingly
      useful as investigators continue to dissect the number of unusual signal
      transduction pathways that control gene expression in this and other related
      species.

PMID- 14712634
TI  - In vitro transcription assays using components from Methanothermobacter
      thermautotrophicus.

PMID- 14712635
TI  - Isolation and characterization of Streptomyces coelicolor RNA polymerase, its
      sigma, and antisigma factors.

PMID- 14712636
TI  - Bacteriophage N4-coded, virion-encapsulated DNA-dependent RNA polymerase.

PMID- 14712637
TI  - Preparation and characterization of recombinant Thermus aquaticus RNA polymerase.

PMID- 14712638
TI  - Purification and assay of upstream activation factor, core factor, Rrn3p, and
      yeast RNA polymerase I.

PMID- 14712639
TI  - Purification and transcriptional analysis of RNA polymerase I holoenzymes from
      broccoli (Brassica oleracea) and frog (Xenopus laevis).

PMID- 14712640
TI  - Assays and affinity purification of biotinylated and nonbiotinylated forms of
      double-tagged core RNA polymerase II from Saccharomyces cerevisiae.

PMID- 14712641
TI  - Dephosphorylation of the carboxyl-terminal domain of RNA polymerase II.

PMID- 14712642
TI  - RNA polymerase III from the fission yeast, Schizosaccharomyces pombe.

PMID- 14712643
TI  - Purification of highly-active and soluble Escherichia coli sigma 70 polypeptide
      overproduced at low temperature.

PMID- 14712644
TI  - Expression, purification of, and monoclonal antibodies to sigma factors from
      Escherichia coli.

PMID- 14712645
TI  - Studying sigma-core interactions in Escherichia coli RNA polymerase by
      electrophoretic shift assays and luminescence resonance energy transfer.

PMID- 14712646
TI  - Assay of Escherichia coli RNA polymerase: sigma-core interactions.

PMID- 14712647
TI  - Purification and characterization of bacteriophage-encoded inhibitors of host RNA
      polymerase: T-odd phage gp2-like proteins.

PMID- 14712648
TI  - A procedure for identifying loosely conserved protein-binding DNA sequences.

PMID- 14712649
TI  - Computational detection of vertebrate RNA polymerase II promoters.

PMID- 14712650
TI  - Detection of DNA-binding helix-turn-helix motifs in proteins using the pattern
      dictionary method.

PMID- 14712651
TI  - DNA microarrays and bacterial gene expression.

PMID- 14712652
TI  - Analysis of microarray data for the marA, soxS, and rob regulons of Escherichia
      coli.

PMID- 14712653
TI  - Purification and activity assays of RapA, the RNA polymerase-associated homolog
      of the SWI/SNF protein superfamily.

PMID- 14712654
TI  - Escherichia coli proteins eluted from mono Q chromatography, a final step during
      RNA polymerase purification procedure.

PMID- 14712655
TI  - Techniques for studying the oxygen-sensitive transcription factor FNR from
      Escherichia coli.
AB  - A large variety of techniques can be adapted for use with oxygen-sensitive
      samples. The growth of cells and in vivo analyses, as well as protein
      purification and in vitro assays, can be executed either by performing necessary
      steps in anaerobic environments (ranging from simple closed containers to the
      anaerobic chamber) or by circumventing the need for anaerobiosis with the use of
      oxygen-resistant protein variants.

PMID- 14712656
TI  - Assay of transcription modulation by SpoOA of Bacillus subtilis.

PMID- 14712657
TI  - Assay of prokaryotic enhancer activity over a distance in vitro.

PMID- 14712658
TI  - DnaA as a transcription regulator.

PMID- 14712659
TI  - Analysis of transcription factor interactions at sedimentation equilibrium.

PMID- 14712660
TI  - Single-molecule studies of DNA architectural changes induced by regulatory
      proteins.

PMID- 14712661
TI  - Assay of an intrinsic acetyltransferase activity of the transcriptional
      coactivator CIITA.

PMID- 14712662
TI  - Purification and assay of Saccharomyces cerevisiae phosphatase that acts on the C
      terminal domain of the largest subunit of RNA polymerase II.

PMID- 14712663
TI  - Functional analysis of transcription factors CREB and CREM.

PMID- 14712664
TI  - Functional analysis of TFIID components using conditional mutants.

PMID- 14712665
TI  - Immunoaffinity purification of mammalian protein complexes.

PMID- 14712666
TI  - Interaction of Gal4p with components of transcription machinery in vivo.

PMID- 14712667
TI  - Dominant-negative mutants of helix-loop-helix proteins: transcriptional
      inhibition.

PMID- 14712668
TI  - Purification and transcription repression by negative cofactor 2.

PMID- 14712669
TI  - Hap1p photofootprinting as an in vivo assay of repression mechanism in
      Saccharomyces cerevisiae.

PMID- 14712670
TI  - Analysis of activator-dependent transcription reinitiation in vitro.

PMID- 14712671
TI  - Molecular analysis of activator engagement with RNA polymerase.

PMID- 14712672
TI  - Purification and protein interaction assays of the VP16C transcription activation
      domain.

PMID- 14712673
TI  - Rapid quench mixing to quantify kinetics of steps in association of Escherichia
      coli RNA polymerase with promoter DNA.

PMID- 14712674
TI  - Determination of RNA polymerase binding and isomerization parameters by measuring
      abortive initiations.

PMID- 14712675
TI  - Probing the role of region 2 of Escherichia coli sigma 70 in nucleation and
      maintenance of the single-stranded DNA bubble in RNA polymerase-promoter open
      complexes.

PMID- 14712676
TI  - On the use of 2-aminopurine as a probe for base pair opening during transcription
      initiation.

PMID- 14712677
TI  - Single-molecule DNA nanomanipulation: detection of promoter-unwinding events by
      RNA polymerase.

PMID- 14712678
TI  - Simple fluorescence assays probing conformational changes of Escherichia coli RNA
      polymerase during transcription initiation.

PMID- 14712679
TI  - Measuring control of transcription initiation by changing concentrations of
      nucleotides and their derivatives.

PMID- 14712680
TI  - Identification of promoters of Escherichia coli and phage in transcription
      section plasmid pSA850.

PMID- 14712681
TI  - Enhancer-dependent transcription by bacterial RNA polymerase: the beta subunit
      downstream lobe is used by sigma 54 during open promoter complex formation.

PMID- 14712682
TI  - Mutational analysis and structure of the phage SP6 promoter.

PMID- 14712683
TI  - Fluorescence methods for studying the kinetics and thermodynamics of
      transcription initiation.

PMID- 14712684
TI  - In vitro studies of the early steps of RNA synthesis by human RNA polymerase II.

PMID- 14712685
TI  - Site-specific protein-DNA photocross-linking of purified complexes: topology of
      the RNA polymerase II transcription initiation complex.

PMID- 14712686
TI  - Assay of promoter melting and extension of mRNA: role of TFIIH subunits.

PMID- 14712687
TI  - Assays for investigating the mechanism of promoter escape by RNA polymerase II.

PMID- 14712688
TI  - On models and methods for studying polymerase translocation.

PMID- 14712689
TI  - Evaluation of fluorescence spectroscopy methods for mapping melted regions of DNA
      along the transcription pathway.

PMID- 14712690
TI  - Single DNA molecule analysis of transcription complexes.

PMID- 14712691
TI  - Assay for movements of RNA polymerase along DNA.

PMID- 14712692
TI  - Kinetics of multisubunit RNA polymerases: experimental methods and data analysis.

PMID- 14712693
TI  - Principles and methods of affinity cleavage in studying transcription.

PMID- 14712694
TI  - Iodine-125 radioprobing of E. coli RNA polymerase transcription elongation
      complexes.

PMID- 14712695
TI  - Formation of long DNA templates containing site-specific alkane-disulfide DNA
      interstrand cross-links for use in transcription reactions.

PMID- 14712696
TI  - Probing the organization of transcription complexes using photoreactive 4-thio
      substituted analogs of uracil and thymidine.

PMID- 14712697
TI  - Fluorescence resonance energy transfer (FRET) in analysis of transcription
      complex structure and function.

PMID- 14712698
TI  - Methods of walking with the RNA polymerase.

PMID- 14712699
TI  - Stepwise walking and cross-linking of RNA with elongating T7 RNA polymerase.

PMID- 14712700
TI  - Characterization of protein-nucleic acid interactions that are required for
      transcription processivity.

PMID- 14712701
TI  - Strategies and methods of cross-linking of RNA polymerase active center.

PMID- 14712702
TI  - Using a lac repressor roadblock to analyze the E. coli transcription elongation
      complex.

PMID- 14712703
TI  - Biochemical assays of Gre factors of Thermus thermophilus.

PMID- 14712704
TI  - Engineering of elongation complexes of bacterial and yeast RNA polymerases.

PMID- 14712705
TI  - Assay of transient state kinetics of RNA polymerase II elongation.

PMID- 14712706
TI  - Analysis of RNA polymerase II elongation in vitro.

PMID- 14712707
TI  - Preparation and assay of RNA polymerase II elongation factors elongin and ELL.

PMID- 14712708
TI  - Use of RNA yeast polymerase II mutants in studying transcription elongation.

PMID- 14712709
TI  - Acetylation of human AP-endonuclease 1, a critical enzyme in DNA repair and
      transcription regulation.

PMID- 14712710
TI  - Characterization of transcription-repair coupling factors in E. coli and humans.

PMID- 14712711
TI  - Techniques to analyze the HIV-1 Tat and TAR RNA-dependent recruitment and
      activation of the cyclin T1: CDK9 (P-TEFb) transcription elongation factor.

PMID- 14712712
TI  - Assay of intrinsic transcript termination by E. coli RNA polymerase on single
      stranded and double-stranded DNA templates.

PMID- 14712713
TI  - Bacteriophage HK022 Nun protein: a specific transcription termination factor that
      excludes bacteriophage lambda.

PMID- 14712714
TI  - Assay of transcription termination by ribosomal protein L4.

PMID- 14712715
TI  - Analysis of the intrinsic transcription termination mechanism and its control.

PMID- 14712716
TI  - Rho's role in transcription attenuation in the tna operon of E. coli.

PMID- 14712717
TI  - Role of RNA structure in transcription attenuation in Bacillus subtilis: the
      trpEDCFBA operon as a model system.

PMID- 14712718
TI  - TRAP-RNA interactions involved in regulating transcription attenuation of the
      Bacillus subtilis trp operon.

PMID- 14712719
TI  - Analyzing transcription antitermination in lambdoid phages encoding toxin genes.

PMID- 14712720
TI  - Genetic and biochemical strategies to elucidate the architecture and targets of a
      processive transcription antiterminator from bacteriophage lambda.

PMID- 14712721
TI  - Assay of transcription antitermination by proteins of the CspA family.

PMID- 14712722
TI  - Assay of antitermination of ribosomal RNA transcription.

PMID- 14712723
TI  - Purification of elongating RNA polymerase II and other factors from yeast
      chromatin.

PMID- 14712724
TI  - Chromatin assembly in vitro with purified recombinant ACF and NAP-1.

PMID- 14712725
TI  - Tying C' ends of H2A and H2B using a molecular glue, tissue-type
      transglutaminase.

PMID- 14712726
TI  - Chromatin decompaction method by HMGN proteins.

PMID- 14712727
TI  - Assay of activator recruitment of chromatin-modifying complexes.

PMID- 14712728
TI  - Insights into structure and function of GCN5/PCAF and yEsa 1 histone
      acetyltransferase domains:.

PMID- 14712729
TI  - Assay of the fate of the nucleosome during transcription by RNA polymerase II.

PMID- 14712730
TI  - Probing chromatin immunoprecipitates with CpG-island microarrays to identify
      genomic sites occupied by DNA-binding proteins.

PMID- 14712731
TI  - Isolation of RNA polymerase suppressors of a (p)ppGpp deficiency.

PMID- 14712732
TI  - Analysis of transcriptional repression by Mig1 in Saccharomyces cerevisiae using
      a reporter assay.

PMID- 14712733
TI  - Mutational analysis of Drosophila RNA polymerase II.

PMID- 14712734
TI  - COBRA for state and local governmental plans.
AB  - This article summarizes the statutory requirements for COBRA continuation
      coverage under the Public Health Service Act (PHSA) and notes where those
      requirements differ from those under the Employee Retirement Income Security Act
      (ERISA) and the Internal Revenue Code, and then examines two important areas that
      distinguish private and public sector COBRA--enforcement and regulatory guidance.

PMID- 14712735
TI  - New York State's solution to rising WC prescription drug costs: ONECARD Rx.
AB  - Double-digit increases in workers' compensation medical costs, especially
      prescription drugs, are back. Work-related injuries and illnesses are increasing
      8-12% yearly. This article is a summary of New York State government's integrated
      workers' compensation/health insurance pharmacy benefit program, ONECARD Rx.

PMID- 14712736
TI  - Public sector health insurance trusts.
AB  - Public sector associations have successfully developed and run employee health
      insurance pools for almost 30 years, providing members with savings and
      flexibility not available from commercial health insurance carriers. This article
      looks at the models, technical tools and governance philosophy that have
      contributed to their success in a very challenging business environment.

PMID- 14712738
TI  - Retirements at risk: employees lack a comprehensive, realistic view of resources
      and needs.
AB  - Employees who are following conventional retirement-planning advice will be in
      for a rude awakening as they approach retirement and discover that they can't
      afford to retire just yet or are likely to outlive their retirement funds. The
      article discusses how we have arrived at this point, what the implications are,
      and what both employers and employees can do to remedy the situation.

PMID- 14712737
TI  - Fraud and fiduciary liability.
AB  - All employee benefit plans are potential targets of fraudulent schemes. Smaller
      plans are targeted by unscrupulous brokers and promoters selling fraudulent
      policies; plans large enough to be self-insured face greater risks of fraud by
      providers and participants misrepresenting claims. Plan trustees, administrators
      and consultants should be alert to the many ways fraudulent schemes manifest
      themselves and to the legal remedies available; establish investigative programs
      to detect and discourage fraud; and promote education and plan incentives for
      participants to report fraud.

PMID- 14712739
TI  - Practical steps to controlling medical costs.
AB  - There are no silver bullets to control medical costs. And some costs are beyond
      plan sponsors' control. But plan sponsors can reduce the annual medical trend by
      taking control of the high-cost drivers of medical expenses while, at the same
      time, improving employees' perception of the medical plan. Patient care
      management, disease management and health status improvement support (with member
      involvement) are key.

PMID- 14712740
TI  - Importing prescription drugs: risky business.
AB  - As prescription drug costs continue to soar, some employee benefit plans are
      looking beyond U.S. borders. This article outlines the regulatory framework
      governing importation of prescription drugs from foreign countries, additional
      concerns raised by the fiduciary requirements of ERISA, and significant
      legislative proposals in Congress that seek to address the issue of the high cost
      of prescription drugs in the United States.

PMID- 14712741
TI  - The peak of construction. After years of stagnant hospital growth, Colorado sees
      boom in healthcare construction as enterprising companies pan for gold.
AB  - As Denver experienced a population boom during the '90s, hospital construction
      was at a standstill. Now providers are racing to catch up with demand, reflecting
      a national trend. Four Denver-area facilities, including Sky Ridge Medical
      Center, left, are open or under construction. "Right now, there's nothing like
      this going on anywhere," says Dennis Brimhall, of the University of Colorado
      Hospital.

PMID- 14712742
TI  - Hospital on the block. HHS agrees to sale of troubled Tenet facility to avoid its
      exclusion from Medicare and Medicaid.

PMID- 14712743
TI  - Calls to reform the reform. Democrats set out on difficult task: amending law.

PMID- 14712744
TI  - Wait 'til next year. Congress doesn't pass funding bill but extends benefits for
      mental health patients.

PMID- 14712745
TI  - Settlement in California. Hospital accused of admitting patient to evade law.

PMID- 14712746
TI  - Why healthcare is issue no. 1. A plan to cover the uninsured while giving the
      economy a needed boost.

PMID- 14712747
TI  - Excellence abounds. Sodexho honors providers that go the extra mile.

PMID- 14712748
TI  - Got a beef? Try arbitration.

PMID- 14712749
TI  - Board recertification gets tougher.

PMID- 14712750
TI  - How hard you work.

PMID- 14712751
TI  - What was wrong with my patient?

PMID- 14712752
TI  - Nonbillables. When should patients pay for them?

PMID- 14712753
TI  - "I'm a doctor, not a nanny".

PMID- 14712754
TI  - The real reason doctors are unhappy.

PMID- 14712756
TI  - Insights into problems obtaining care believed necessary as measured by the
      Medicaid Consumer Assessment of Health Plans Survey (CAHPS).
AB  - BACKGROUND: The Consumer Assessment of Health Plans Survey (CAHPS) is widely used
      to evaluate health plans; however there are few reports of Medicaid health plan
      efforts to improve performance as measured by CAHPS. OBJECTIVE: Data from CAHPS
      were analyzed to help plan administrators determine how they might address member
      reports of problems obtaining care they or their doctor believed necessary. STUDY
      DESIGN: Secondary analysis of cross-sectional survey data obtained from adults
      and children enrolled in 3 Medicaid health plans. METHODS: Cross-tabulations of
      CAHPS responses and follow-up questions asking enrollees to describe the problems
      they had obtaining care believed necessary. RESULTS: Problems obtaining care
      believed necessary were among the most frequently reported problems (13%-17% of
      adults, 9% of children). Problems obtaining a satisfactory personal doctor;
      receiving help when calling a physician's office; securing routine, urgent, and
      specialist care appointments as soon as desired; receiving referrals to
      specialists; obtaining behavioral health services and prescription medications;
      and problems with doctor communication were related to problems obtaining care
      believed necessary. Enrollees' descriptions of the problems corroborated observed
      relationships between CAHPS responses, and revealed dissatisfaction with doctors'
      care and lack of coverage for various services as additional contributors.
      CONCLUSIONS: Analyses of relationships between enrollee-reported problems
      obtaining care believed necessary and their responses to other CAHPS items and
      follow-up questions identified a number of plausible causes of this problem.
      Given the multifaceted nature of problems with obtaining care believed necessary,
      a plan of action that might substantially improve this predicament was not
      apparent. Additional information about how health plan operations influence CAHPS
      results and the effect of health plan interventions on CAHPS measurements are
      needed to facilitate use of these data for quality improvement.

PMID- 14712755
TI  - Verification of a decision analytic model assumption using real-world practice
      data: implications for the cost effectiveness of cyclo-oxygenase 2 inhibitors
      (COX-2s).
AB  - OBJECTIVE: To verify the gastroprotective agent (GPA) rate assumption used in
      cost-effectiveness models for cyclo-oxygenase 2 inhibitors (COX-2s) and to re
      estimate model outcomes using GPA rates from actual practice. METHODS:
      Prescription and medical claims data obtained from January 1, 1999, through May
      31, 2001, from a large preferred provider organization in the Midwest, were used
      to estimate GPA rates within 3 groups of patients aged at least 18 years who were
      new to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2
      therapy: all new NSAID users, new NSAID users with a diagnosis of rheumatoid
      arthritis (RA) or osteoarthritis (OA), and a matched cohort of new NSAID users.
      RESULTS: Of the more than 319,000 members with at least 1 day of eligibility,
      1900 met the study inclusion criteria for new NSAID users, 289 had a diagnosis of
      OA or RA, and 1232 were included in the matched cohort. Gastroprotective agent
      estimates for nonselective NSAID and COX-2 users were consistent across all 3
      samples (all new NSAID users, new NSAID users with a diagnosis of OA or RA, and
      the matched cohort), with COX-2 GPA rates of 22%, 21%, and 20%, and nonselective
      NSAID GPA rates of 15%, 15%, and 18%, respectively. Re-estimation of the cost
      effectiveness model increased the cost per year of life saved for COX-2s from
      $18,614 to more than $100,000. CONCLUSIONS: Contrary to COX-2 cost-effectiveness
      model assumptions, the rate of GPA use is positive and marginally higher among
      COX-2 users than among nonselective NSAID users. These findings call into
      question the use of expert opinion in estimating practice pattern model inputs
      prior to a product's use in clinical practice. A re-evaluation of COX-2 cost
      effectiveness models is warranted.

PMID- 14712757
TI  - Do quality improvement strategies for Medicaid enrollees differ in Medicaid
      dominant versus commercial managed care organizations?
AB  - OBJECTIVE: To examine whether it matters, in terms of quality improvement
      initiatives and access to commercial networks, whether states contract with
      Medicaid-dominant or commercial managed care plans. STUDY DESIGN: A 2001
      telephone survey of Medicaid managed care plans in 11 states that together
      account for about half of the national Medicaid managed care enrollment. METHODS:
      The survey was developed in consultation with a panel of individuals
      knowledgeable about Medicaid managed care. Information on plan characteristics
      and network design was obtained from the plan CEO or person most knowledgeable
      about the topics. The rest of the data were obtained from the person the CEO
      named as most knowledgeable about quality improvement initiatives. RESULTS:
      Surveyed plans reported an extensive array of quality improvement initiatives.
      Programs are in many ways similar across Medicaid-dominant and commercial plans.
      Medicaid-dominant plans tend to specialize more in conditions of greatest
      priority to Medicaid beneficiaries. Commercial plans tend to develop programs for
      accreditation by the National Committee for Quality Assurance, and to limit
      measurement specific to the Medicaid population. They draw on their commercial
      networks to support the Medicaid product line, but how much they expand provider
      access is not clear. Both types of programs face barriers that limit the
      effectiveness of the plans' initiatives. CONCLUSION: This study shows extensive
      development of quality initiatives in Medicaid managed care plans, with limited
      differences across Medicaid-dominant and commercial plans.

PMID- 14712758
TI  - Availability of nutrition services for Medicaid recipients in the northeastern
      United States: lack of uniformity and the positive effect of managed care.
AB  - OBJECTIVES: To evaluate third-party coverage of medical nutrition therapy for the
      Medicaid population, among whom obesity is a common health problem, and to
      compare coverage in managed care Medicaid programs with that in fee-for-service
      state Medicaid programs. METHODS: Fifty-four Medicaid organizations in 14 states
      were surveyed by telephone and asked about their provision of nutrition
      counseling to members. RESULTS: Overall, similar percentages of state Medicaid
      programs and Medicaid managed care organizations (MCOs) reimbursed for nutrition
      counseling; significantly more Medicaid MCOs reimbursed for this service for
      treatment of obesity alone. Analysis of Medicaid MCO responses by plan size
      failed to show a difference in the nutrition services offered. CONCLUSIONS AND
      RECOMMENDATIONS: Nutritionist consultation, an inexpensive and effective
      intervention for treatment of obesity, is not uniformly available to Medicaid
      patients. The inclusion of managed care in Medicaid has increased access to this
      service in the northeastern United States. We propose that all Medicaid
      recipients should have access to visits with a registered dietician or certified
      nutritionist either as part of a defined benefit structure or through a disease
      management program for obesity.

PMID- 14712759
TI  - Celiac disease.
AB  - Timely diagnosis and treatment of celiac disease is important not only to improve
      the immediate quality of life of the patient but also to decrease the long-term
      risks of untreated celiac disease. A large Finnish study showed that the 5-year
      survival among patients who strictly adhered to a gluten-free diet was similar to
      that of the general population. Growth and development in infants and children
      proceed normally with continued gluten avoidance, and in adults many of the
      disease complications including osteopenia are avoided. However, peripheral
      neuropathy, ataxia, and severe osteopenia, particularly in the setting of
      secondary hyperparathyroidism, usually persist. Enteropathyassociated T-cell
      lymphoma is widely recognized as a complication of celiac disease, and gluten
      restriction has been shown to significantly decrease the risk of this malignancy
      to the level of the general population. Whether gluten restriction is beneficial
      or should be recommended for patients with asymptomatic disease remains
      controversial. However, the available evidence suggests that this treatment is
      always indicated in patients showing celiac enteropathy, at least to prevent the
      possible long-term complications of this condition. Despite a dearth of evidence
      presently to support population-wide screening for celiac disease, patients at
      high-risk for celiac disease should be screened based on symptoms, family
      history, and associated conditions, as morbidity from subclinical disease in
      young patients has been demonstrated.

PMID- 14712760
TI  - [DNA methylation and cancer--DNA methylation as a target of cancer chemotherapy].
AB  - Aberrant epigenetic information, represented by aberrant DNA methylation, plays a
      large role in carcinogenesis. Hypermethylation of CpG islands in promoter regions
      can lead to silencing of tumor-suppressor genes, and hypomethylation of the
      genome could lead to its instability. Epigenetic information is inherited from a
      cell to its daughter cells without any decay in somatic cells, but shows dynamic
      changes during embryonic development. Based on the possibility that epigenetic
      information can be theoretically reversed, attempts are being made to use the
      aberrant epigenetic information as therapeutic targets. A demethylating agent, 5
      aza-2'-deoxycytidine, has been reported to be effective for some hematological
      malignancies, and its derivatives are being developed. Finally, reports are
      coming out on methods that can induce sequence-specific methylation changes.
      Rapid progress in this field is expected.

PMID- 14712761
TI  - [Heavy charged particle radiotherapy--proton beam].
AB  - Proton beam therapy (PBT) makes it possible to deliver a higher concentration of
      radiation to the tumor by its Bragg-peak, and is easy to utilize due to its
      identical biological characteristics with X-rays. PBT has a half-century history,
      and more than 35,000 patients have been reported as having had treatments with
      proton beams worldwide. The historic change to this therapy occurred in the
      1990s, when the Loma Linda University Medical Center began clinical activity as
      the first hospital in the world to utilize a medically dedicated proton therapy
      facility. Since then, similar hospital-based medically dedicated facilities have
      been constructed. Results from around the world have shown the therapeutic
      superiority of PBT over alternative treatment options for ocular melanoma, skull
      base sarcoma, head and neck cancer, lung cancer, esophageal cancer,
      hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further
      advancement both clinically and technologically.

PMID- 14712762
TI  - [Heavy charged particles radiotherapy--mainly carbon ion beams].
AB  - Carbon ion beams have superior dose distribution allowing selective irradiation
      to the tumor while minimizing irradiation to the surrounding normal tissues.
      Furthermore, carbon ions produce an increased density of local energy deposition
      with high-energy transfer (LET) components, resulting in radiobiological
      advantages. Stimulated by the favorable results in fast neutrons, helium ions,
      and neon ions, a clinical trial of carbon ion therapy was begun at the National
      Institute of Radiological Sciences in 1994. Carbon ions were generated by a
      medically dedicated accelerator (HIMAC, Heavy Ion Medical Accelerator in Chiba,
      Japan), which was the world's first heavy ion accelerator complex dedicated to
      medical use in a hospital environment. In general, patients were selected for
      treatment when their tumors could not be expected to respond favorably to
      conventional forms of therapy. A total of 1601 patients were registered in this
      clinical trial so far. The normal tissue reactions were acceptable, and there
      were no carbon related deaths. Carbon ion radiotherapy seemed to be a clinically
      feasible curative treatment modality, and appears to offer improved results not
      only over conventional X-rays but also even over surgery in some selected
      carcinomas.

PMID- 14712763
TI  - [Gamma knife radiosurgery].
AB  - Gamma knife radiosurgery has become a new treatment modality in the field of
      neurosurgery since the first gamma knife was brought into Japan in 1990. Advances
      in applications of new indications and long-term results have been continued to
      evolve during the past 12 years. Based on the experience of more than 4,500 cases
      treated by gamma knife at Komaki City Hospital, long-term results of
      arteriovenous malformations (AVMs), metastatic brain tumors, acoustic neurinomas,
      meningiomas and trigeminal neuralgias are presented. Radiosurgery has become a
      novel treatment modality, especially for AVM, acoustic neurinoma and meningioma,
      which were once only treatable by conventional surgery, and shows a high cure
      rate in AVM cases and high control rate in benign tumors without major
      complications. The effects of radiosurgery for metastatic brain tumors have been
      thought to be superior to fractionated radiotherapy due to high response and
      control rates, and patients showed improved quality of life although no
      prolongation of the life span was obtained. Gamma knife treatment for trigeminal
      neuralgia has been shown to be effective and less invasive than microvascular
      decompression, and is useful for cases resistant to conventional therapies and as
      an initial treatment as well.

PMID- 14712764
TI  - [3D-CRT and intensity modulated radiation therapy (IMRT)].
AB  - Three-dimensional conformal radiation therapy (3D-CRT) conforms a high dose
      region closer to the target volume than does 2D radiation therapy. IMRT is the
      advanced form of 3D-CRT. With IMRT technique, using multiple intensity modulated
      beams, one can deliver a high dose of radiation to the target and a low dose to
      the surrounding normal structures. IMRT planning provides improved tumor target
      coverage when compared to 3D-CRT treatment planning. There is significant sparing
      of critical structures and other normal tissues. IMRT also produces dose
      distributions capable of delivering different dose prescriptions to multiple
      targets, providing a new opportunity for differential dose painting to increase
      the dose selectively to specific image-defined regions. Preliminary findings
      indicate that IMRT is a new clinically feasible tool in radiation oncology. The
      initial results of clinical studies demonstrate reduced xerostomia in head and
      neck cancer and also effectively reduced acute and late occurring toxicities,
      improving the QOL of patients treated for prostate cancer. According to these
      studies, IMRT will allow dose escalation, leading to better tumor control without
      normal tissue damage. On the other hand, there are some problems for IMRT in
      Japan: There are few medical physicists, which results in radiation technologists
      playing most clinical technological roles, including some dosimetrical and
      physical activities. Social recognition and economical and legal support for
      medical physicists should be established in providing better patient care
      services.

PMID- 14712765
TI  - [Advances in brachytherapy--focusing on the permanent implant for early prostate
      carcinoma].
AB  - Even in the modern era of advanced external radiotherapy, brachytherapy is an
      important and useful modality of radiotherapy. In North America and Europe, it
      has been noted that the proportion of prostate cancer patients treated by HDR or
      LDR interstitial brachytherapy is rapidly increasing, as it offers several
      practical and theoretical advantages over external radiotherapy. HDR treatment
      with 192Ir remote afterloader provides an optimized dose distribution controlled
      by an accurate dwell time and position of 192Ir source. LDR brachytherapy is a
      simple, minimally invasive, and outpatient based procedure that avoids
      hospitalization and allows the patient an early recovery and rapid return to
      normal activities. It has produced good 10-year outcome with relatively low
      morbidity. Although in Japan this treatment was behind North America and Europe,
      the 125I-seed source was approved by the Japanese FDA and a rule for patient
      discharge was developed recently. The first case was treated in September 2003
      and this treatment is expected to become an important option for early prostate
      cancer. Several areas of brachytherapy including treatment planning, choice of
      radionuclide, treatment procedure, and treatment outcome are discussed in this
      paper.

PMID- 14712766
TI  - [Local administration of adriamycin (ADM) for malignant pleural effusion and
      pericardiac effusion in breast cancer].
AB  - We examined the efficacy, toxicity, and survival rate of patients treated with
      local administration of adriamycin (ADM) for malignant pleural effusion and
      pericardial effusion in breast cancer. From May 1996 to December 2002, we
      injected ADM into the pleural cavity for 21 courses and into the pericardial
      cavity for 2 courses in 18 patients. Thirteen patients showed CR (including 2
      cases were injected into pericardial cavity), 2 PR, and 4 PD, and the overall
      response rate was 78.9%. Toxicities included nausea/vomiting, elevated fever,
      chest pain, and so on in 15 patients (83.3%). No severe toxicities, however, were
      observed. The overall survival rate after the removal of the drainage tube was
      42.5% at 1 year and 16.5% at 2 years. The survival in patients with a first
      recurrence, and CR or PR was significantly better than other patients. We
      conclude that local administration of ADM is useful for treatment, without severe
      toxicities, of malignant pleural effusion and pericardial effusion in breast
      cancer.

PMID- 14712767
TI  - [A retrospective study of advanced ovarian cancer in our ward].
AB  - OBJECTIVE: To evaluate the efficacy of primary treatment for ovarian cancer from
      overall survival and progression-free survival. PATIENTS AND METHODS: A total of
      28 patients with epithelial ovarian cancer in stages III and IV who were
      primarily treated in our ward from 1993 were examined retrospectively. The Kaplan
      Meier method and Harrington-Fleming test were carried out for the cumulative
      survival rate and analysis. RESULTS: There were significant differences in the
      progression-free survival rate depending on whether or not optimal debulking was
      possible through primary treatment (p = 0.0128) and whether the histological
      diagnosis was serous adenocarcinoma (p = 0.038). In the serous adenocarcinoma
      group, the periods of both overall survival and progression-free survival were
      longer in treatment with taxanes and platinum than by other regimens, but in the
      endometrioid adenocarcinoma group, the period of progression-free survival was
      very short. CONCLUSIONS: Optimal debulking through primary treatment is critical
      in advanced ovarian cancer. Therapy with taxanes and platinum is efficacious for
      serous adenocarcinoma. The chemo-sensitivity of endometrioid adenocarcinoma is
      high, but the chemotherapeutic effect is only temporary.

PMID- 14712768
TI  - [Effect and mechanism of orally administered leucovorin/5-fluorouracil on colon
      cancer].
AB  - Leucovorin (LV)/5-fluorouracil combination is one of the first-line forms of
      chemotherapy for colorectal cancer, and in this regimen it was recommended that 5
      FU be infused continuously from the venous route. However, since this regimen
      limits the patients' ADL, oral administration is preferable. The purpose of this
      study is to elucidate the mechanisms of orally-administered LV/5-FU. MATERIAL AND
      METHODS: The Gastrostomy was performed, and 1 x 10(6) of colon 26 was
      transplanted subcutaneously in CDF1 mice. In the continuous administration group,
      either 10, 20, 40 mg/kg of 5-FU and 100 mg/kg of LV were continuously infused for
      7 days following gastrostomy using a microinfusion pump (n = 6). In the single
      infusion group, either 10, 20, 40 mg/kg of 5-FU was infused once a day for 7 days
      after gastrostomy concomitant with LV (n = 6). The other 6 animals served as the
      control, and LV alone was infused in this group. Tumor volume, thymidylate
      synthase inhibition rate (TSIR), incorporation of 5-FU into RNA (F-RNA) and body
      weight were measured at the end of the treatment. During the experimental period,
      mice were given free access to chow and water. RESULTS: The tumor volume
      suppression rate was significantly higher along with the amount of 5-FU. However,
      there was no significant difference between continuous and single infusion
      groups. TSIR was higher in the continuous group at the dose of 20 and 40 mg/kg.
      In contrast, F-RNA was higher in the single group at the dose of 20 and 40 mg/kg.
      Significant body weight loss was not recognized in any group. CONCLUSION: From
      these data, single administration of 5-FU is more effective for RNA dysfunction.
      On the other hand, continuous infusion is more damaging to DNA duplication. In
      summary, since the mechanism of the antitumor effect differs with the
      administration method, it is important to understand this mechanism.

PMID- 14712769
TI  - [Support of TS-1, 5-FU preparation containing potent DPD inhibitor by
      determination of urinary uracil/serum 5-FU clearance].
AB  - Though FU-derived anticancer agents are metabolized and detoxicated by
      dihydropyrimidine dehydrogenase (DPD), its wide distribution of activity is
      concerned primarily in the antitumor effects or side effects of 5-FU. In recent
      years, it has become possible to predict the metabolism of FU-derived anticancer
      agents by DPD activity through the determination of urinary uracil levels. In the
      present study, therefore, we examined whether or not urinary uracil levels could
      be used as a predictor for as certaining the efficacy and/or side effects of TS
      1, which contains a potent DPD inhibitor. Consequently, the following
      relationship was revealed to exist between urinary uracil levels and clinical
      effects of TS-1: 1) The effect of TS-1 administration was generally good in
      patients whose uracil level was within the standard values with no presentation
      of serious side effects. 2) The administration of TS-1 was also useful even in
      patients whose uracil levels were below the standard value. 3) Though no side
      effects were observed when a conventional FU-derived anticancer agent was
      administered to patients showing an urinary uracil level below the standard
      value, some side effects appeared when TS-1 was administered. Under present
      circumstances where understanding of genome diagnosis and establishment of
      informed consent are rather difficult, this approach of predicting DPD activities
      through the determination of urinary uracil levels seems to be of help for
      deciding a therapeutic regimen based on the patient's constitutional features
      when a cancer chemotherapy with TS-1 is performed.

PMID- 14712770
TI  - [A clinical study of neoadjuvant radiochemotherapy with docetaxel and cisplatin
      for oral cancers].
AB  - Docetaxel is classified among the microtubule-inhibiting compounds called
      taxanes, which are currently used as agents to treat head and neck cancers. To
      investigate the efficacy and safety of a neoadjuvant radiation therapy combined
      with docetaxel/cisplatin, we used this combination to treat 6 patients with oral
      squamous cell carcinoma. The patients received a low-dose fraction of docetaxel
      (20 mg/m2/week; total dose: 123.0 +/- 35.0 mg) and cisplatin (5 mg/m2/day, 5 days
      a week; total dose: 160.0 +/- 42.1 mg) combined with simultaneous irradiation of
      40 Gy. Of the 6 patients, 5 (83.3%) showed a partial response (PR) and 1 showed
      no response (NC). Pathological efficacy was revealed in 4 patients (66.7%). All
      patients experienced stomatitis over grade 2, and 4 experienced neutropenia.

PMID- 14712771
TI  - [A case of parotid carcinoma with hepatic metastasis that responded remarkably to
      combination chemotherapy of docetaxel, cisplatin and 5-fluorouracil].
AB  - A patient who had parotid gland carcinoma with hepatic metastasis (T4N2bM1)
      underwent 3 cycles of neoadjuvant chemotherapy with docetaxel, cisplatin and
      fluorouracil (TPF). After this treatment, the patient showed a PR in the primary
      site and a CR in the hepatic metastasis. Left total parotidectomy and modified
      radical neck dissection were then performed followed by postoperative irradiation
      of 40 Gy. No recurrence in the primary site or the neck was seen, but in the
      metastatic site a recurrence was observed at 8 weeks after the first
      chemotherapy. The same chemotherapy is now applied in an outpatient setting.
      Toxicities with neutropenia, nausea and vomiting of CTC Grade 3 were observed,
      but these toxicities were mild and manageable. TPF is considered to show clinical
      activity for advanced parotid gland carcinoma, and we consider further
      investigation necessary.

PMID- 14712772
TI  - [A case of advanced gastric cancer with multiple liver metastases responding
      completely to hepatic arterial infusion and systemic chemotherapies].
AB  - A 41-year-old male complaining of epigastric discomfort visited another hospital
      for a medical checkup. Gastrointestinal fiberscopic examination revealed a type 3
      lesion on the lesser curvature of the lower portion, and biopsy specimens showed
      tubular adenocarcinoma. Abdominal CT demonstrated multiple liver metastases.
      After receiving a low-dose FP chemotherapy via IVH catheter for 1 week, the
      patient undertook a distal gastrectomy accompanied by D2 lymph node dissection.
      From the 19th postoperative day (POD), hepatic arterial infusion chemotherapy
      (HAIC) using 5-FU (500 mg/day) plus CDDP (10 mg/day) was performed for about 14
      months. On the 47th POD, oral administration of UFT began and continued for 2
      years. After 4 months of HAIC, the metastatic lesions of the liver disappeared
      completely. The patient has been free from recurrence since then for about 2
      years. In the peripheral blood, Th1/Th2 ratio and activity of NK/LAK (IL-2
      induced) kept increasing during this period. IHAC using 5-FU plus CDDP seems to
      be an efficient and worthy therapeutic modality if there are no other lesions
      except multiple liver metastases and a curative gastric resection is indicated.

PMID- 14712773
TI  - [Concurrent chemoradiation experience of recurrent gastric cancers resistant to
      TS-1].
AB  - We report our experience with concurrent chemoradiation for recurrent gastric
      cancers resistant to TS-1. From April 2000 to March 2003, we treated 10
      consecutive patients with radiation and the concurrent single chemotherapy agent
      of TS-1 or CPT-11. Of the 10 patients, 3 (30%) had a complete response, 4 (40%) a
      partial response, and 3 (30%) stable disease, yielding an overall response rate
      of 70% (7/10). Three patients are alive and cancer-free, 5 patients died with
      cancers, and 2 patients are living with cancers as outpatients. The clinical
      benefit response was 90% (9/10). No patient has had either acute or late
      complication. Concurrent chemoradiation is feasible and seems to offer good
      results for recurrent gastric cancers resistant to TS-1.

PMID- 14712774
TI  - [Two resected cases of advanced gastric cancer with peritoneal dissemination
      after successful treatment with TS-1 plus low-dose CDDP].
AB  - We report two resected cases of advanced gastric cancer with peritoneal
      dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1
      presented with right hypochondralgia and underwent laparotomy with diagnosis of
      type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was
      judged to be unresectable due to peritoneal dissemination, and chemotherapy was
      performed. At the completion of course 1, he underwent laparotomy again. Although
      the tumor involved the body of the pancreas and transverse colon, there was no
      peritoneal dissemination. Therefore, a total gastrectomy was performed with
      distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node
      dissection. Patient 2 presented with anorexia and was diagnosed with type 3
      gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was
      unresectable due to peritoneal dissemination, and so chemotherapy was performed.
      He underwent laparotomy at the completion of course 3. There was no peritoneal
      dissemination, so a total gastrectomy was performed with cholecystectomy and D2
      lymph node dissection. Both patients remain alive and in good condition without
      any signs of recurrence after surgery.

PMID- 14712775
TI  - [Two cases of non-curatively resected scirrhous gastric cancer that responded
      well to weekly paclitaxel therapy].
AB  - We report 2 cases in which the weekly administration of paclitaxel proved to be
      effective for patients with scirrhous gastric cancer who underwent a curability C
      operation. Weekly paclitaxel therapy was observed to effectively treat peritoneal
      and retroperitoneal dissemination. After this treatment the tumor markers
      decreased markedly. This weekly paclitaxel therapy was observed to cause no
      adverse effects, and thanks to the treatment the patients were able to consume
      normal meals. These patients could also be sufficiently treated as outpatients.
      Weekly paclitaxel therapy is thus considered to be effective for the treatment of
      advanced scirrhous gastric cancer with peritoneal and retroperitoneal
      dissemination.

PMID- 14712776
TI  - [Clinical benefit of bronchial arterial infusion chemotherapy to pulmonary
      metastasis from colorectal cancer--report of two cases].
AB  - Case 1: A 60-year-old woman with sigmoid colon cancer and multiple lung
      metastases developed dyspnea 34 months after sigmoidectomy and following systemic
      chemotherapy. Chest X-ray revealed left atelectasis and obstruction of the left
      main bronchus by lung metastasis, and stenosis of the right main bronchus was
      also suspected. Bronchial arterial infusion of CDDP, 5-FU and MMC relieved the
      atelectasis and dyspnea. The left bronchus remained patent for 12 months. Case 2:
      A 70-year-old man who had a pulmonary recurrence of rectal cancer suffered from
      hemoptysis and dyspnea, which had improved with systemic chemotherapy but then
      become exacerbated again. Bronchoscopic examination revealed intraluminal
      bleeding from a metastatic tumor. The symptoms were relieved after bronchial
      arterial infusion of CDDP, 5-FU and MMC. The diameter of the treated tumor was
      reduced by 15%. Hemoptysis was negligible until he died 8 months later. Bronchial
      arterial infusion chemotherapy for pulmonary metastasis from colorectal cancer is
      clinically beneficial, especially for patients with life-threatening respiratory
      symptoms like airway obstruction or intraluminal bleeding.

PMID- 14712777
TI  - [A case of ovarian cancer with Parkinson's disease treated by combined
      chemotherapy with paclitaxel and carboplatin followed by surgery].
AB  - It is well known that neuropathy, myelopathy, and arthropathy are specific
      adverse effects induced by paclitaxel administration. Parkinson's disease is
      neural degenerative disease, and the influence of paclitaxel administration on
      patients with Parkinson's disease is unknown. We have successfully treated an
      ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined
      chemotherapy after surgery. The patient was a 57-year-old woman with solid and
      cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX
      was elevated. We operated and made a pathological diagnosis of the ovarian tumor
      as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was
      treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5])
      combined chemotherapy for 5 courses. Her status is complete remission. During
      chemotherapy, she had felt the decreased efficacy of her Parkinson's disease
      medication. We could continue chemotherapy by increasing the dose of the
      Parkinson's drug. There is only one case report on the influence of paclitaxel on
      Parkinson's disease, in which the course was similar to the present case.

PMID- 14712778
TI  - [A case of breast cancer with lung and bone metastasis treated successfully by
      oral combination chemotherapy of 5'-deoxy-5-fluorouridine and cyclophosphamide].
AB  - The patient was a 52-year-old woman who underwent left partial mastectomy on
      April 30, 1999. The stage was T0N1bM1 (bone). After operation, adjuvant therapy
      consisting of 6 cycles of CMF therapy and radiation was performed. On September
      2000, the tumor marker (NCC-ST 439) was at a high level. On January 2001, chest
      CT examination revealed multiple lung metastases of the right lobe. Oral
      combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR, 1,200 mg/day) and
      cyclophosphamide (CPA, 100 mg/day) was thus performed, and definite improvement
      resulted in the lung. No adverse reactions occurred except for anemia and
      thrombocytopenia of grade 1. It is suggested that this oral combination
      chemotherapy may be useful for advanced recurrent breast cancer patients and
      applicable in ambulatory chemotherapy administered with consideration for the
      patient's quality of life.

PMID- 14712779
TI  - [A case of undifferentiated bladder carcinoma with axilla lymph node metastasis
      successfully treated with gemcitabine and cisplatin].
AB  - A 68-year-old man diagnosed with undifferentiated bladder carcinoma underwent
      radical cystectomy in another hospital. His clinical staging was T3bN2M0. Four
      months after the operation, he had right axilla lymph node swelling and pain. He
      was referred to our hospital, and diagnosed with axilla lymph node metastasis of
      bladder carcinoma based on test results. Four cycles of GEM and CDDP chemotherapy
      were performed. After the chemotherapy, the metastatic focus disappeared
      completely from the CT scan, and the case was considered to be CR. It is
      suggested that this combination therapy may be useful for bladder carcinoma in
      advanced or metastatic stages.

PMID- 14712780
TI  - [Effects of vascular endothelial growth factor D on the signaling cascade of
      sentinel lymphatic endothelial cells from melanoma patients undergoing sentinel
      lymphadenectomy].
AB  - Advances in surgical treatment, including sentinel lymphadenectomy, permit the
      pathologic staging of regional lymph nodes most likely to contain metastasis by
      identifying afferent lymphatic channels, which specifically drain the primary
      tumor site. Recently, a new member of the angiogenic molecule in VEGF family,
      VEGF-D, has been identified that induces lymphangiogenesis via high-affinity
      binding to VEGFR-3. VEGF-D is predominantly expressed in lymphatic endothelium.
      We have previously developed a novel method for the isolation of anatomically
      defined lymphatic endothelial cells (LECs) from human sentinel lymphatic channel
      during SLN biopsy. The effect of VEGF-D on the extracellular signal-regulated
      kinases (Erk)-1/2 and Akt signaling pathway was examined by Western blot
      analysis. VEGF-D (500 ng/ml) apparently upregulated phospho-p44/phospho-p42
      activity in human isolated LECs by Western blot analysis, while phospho-Akt
      activity was not at all changed by VEGF-D exposure without the change of total
      p44/p42 and Akt expression. U0126 (20 microM), the MEK1/2 inhibitor, could
      completely block the VEGF-D induced phospholylation of Erk1/2 signaling pathway.
      These data demonstrate that VEGF-D induces p44/p42 in human LECs and suggests
      that this signaling pathway activation may be important in LEC biology and
      lymphoangiogenesis, which may lead to the progression of new strategies of cancer
      treatment.

PMID- 14712781
TI  - [The attempt to standardize treatment protocols for cancer-related hypercalcemia:
      developing a data-based flowchart].
AB  - We developed a flowchart for the treatment of cancer-related hypercalcemia based
      on the review of previous reports. The treatment protocols were standardized in
      each group of four different ranges of serum calcium concentration (< 12, 12-14,
      14-16, < 16 mg/dl). In each Ca range, specific treatment was adjusted according
      to the clinical evaluation of symptoms and progression of illness of the
      patients.

PMID- 14712782
TI  - [Development of novel molecular targeted drug, "Iressa", for the treatment of
      malignant diseases--its basic and clinical studies].
AB  - One year has passed since the launch of a new molecular targeted agent, Iressa
      (generic name: Gefitinib), in Japan ahead of other countries in the world.
      Gefitinib is the first selective Epidermal Growth Factor Receptor (EGFR) tyrosine
      kinase inhibitor. Gefitinib was investigated clinically by a single dose
      ascending study and 3-day multiple dosing study in male volunteers in the UK
      initially. On confirmation of tolerability by those studies, 4 Phase I studies
      were conducted in patients with solid tumours generally known to over-express
      EGFR, with a result of 250 mg or 500 mg (oral administration) decided to be
      chosen as the recommended dose for Phase II studies. A Phase II study was then
      conducted in 9 countries including European countries, Australia, and Japan,
      using once daily oral dosing regimen. In this study gefitinib demonstrated
      response rate of 18.4% (19/103), and disease control rate of 54.4% (56/103) in
      advanced non-small cell lung cancer patients (with 1 or 2 previous chemotherapy
      regimens) at a dose level of 250 mg/day. Symptom improvement rate, which was
      determined using lung cancer sub-scale (LCS) for QOL assessment, was 40.3%
      (27/67), and median time to symptom improvement was 8 days (on the initial
      assessment). In 3 months after the launch, 39 lung injury deaths of patients were
      reported including deaths attributed to interstitial pneumonia, which was covered
      broadly by mass media. It is, however, considered that development of Iressa, the
      first EGFR tyrosine kinase inhibitor showing effects on solid tumours, for
      clinical use through assiduous researches on molecular targeted agents has truly
      great significance. This paper gives an overview covering development history to
      date, clinical study results, and post-launch safety reports.

PMID- 14712783
TI  - Pill profits.

PMID- 14712784
TI  - Joint decisions.

PMID- 14712785
TI  - The brainwashing defense.

PMID- 14712786
TI  - Yellow light for a green fuel.

PMID- 14712787
TI  - [Newly diagnosed hypertensive. It calls for treatment immediately with a
      combination ].

PMID- 14712788
TI  - [Synthetic anticoagulation stands the test in internist patients, Thrombosis risk
      in immobilization cut in half].

PMID- 14712789
TI  - [To protect the hypertensive patient from complications. Blood pressure lowering
      is not equal to blood pressure lowering].

PMID- 14712790
TI  - [Coronary stenting. Does AT-1 blocker protect from restenosis?].

PMID- 14712791
TI  - Expression of nerve growth factor in the airways and its possible role in asthma.
AB  - Nerve growth factor (NGF), in addition to its essential role in neuronal growth
      and survival, may also act as an inflammatory mediator. As several animal studies
      have shown, NGF appears to play a part in the development of airway
      hyperresponsiveness and in the increased sympathetic and sensory innervation of
      the lung. It also has a profound effect on airway inflammation and asthma-related
      symptoms. Sources of NGF in the airways are numerous: inflammatory cells
      infiltrated into the bronchial mucosa, and structural cells including lung
      fibroblasts, airway epithelial and smooth muscle cells. These cells, by releasing
      more NGF in inflammatory conditions, may contribute to the increased NGF levels
      observed in bronchoalveolar lavage fluid and serum from patients with asthma.
      Taken together, these results suggest that NGF is an important mediator in both
      inflammation and asthma.

PMID- 14712792
TI  - [Exactness of transcutaneous sonography in the diagnosis of gastric wall
      lesions].
AB  - OBJECTIVE: Our objective was to determine sensitivity, especificity and
      predictive values of transcutaneous sonography for detecting gastric wall
      lesions. MATERIALS AND METHODS: This prospective study was performed from March
      1999 to April 2000 on 150 patients referred for transcutaneous sonography by the
      Endoscopic Service Unit. Sonographic examinations were performed using RT 4000
      General Electric equipment with 5 Mhz transducer and replenishment of stomach
      with fluid. All scanning was done by the same sonographer, who was unaware of
      endoscopic, tomographic, or upper gastrointestinal series features. Results from
      sonography were compared with gastrointestinal tract endoscopy. Sensitivity,
      specificity, and predictive values were determined using contingency statistical
      procedure. Sonographic examination accuracy was calculated evaluating sensitivity
      and specificity confidence intervals (CI). Kappa index was calculated. Diagnostic
      accuracy differences observed between tumoral and non-tumoral lesions by
      sonography were evaluated by chi 2 probe. RESULTS: Sensitivity of 85% (95% CI,
      from 75.2 to 94.8%) and specificity of 90% (95% CI, from 86 to 93.9%) were
      obtained. Positive predictability was 78% and negative predictability was 94%.
      Diagnostic accuracy was 87%. Kappa index was 0.717. There were 35 no false
      positive results (19 tumoral lesions and 16 non-tumoral lesions), seven false
      negative results (one tumoral lesion and six non-tumoral lesions) and 10 false
      positive results (two tumoral lesions and eight non-tumoral lesions). Only one of
      20 tumoral lesions were diagnosed by ultrasound whereas from 22 non-tumoral
      lesions were not diagnosed 6 (chi 2 = 3.74, p > 0.05). CONCLUSION: Transcutaneous
      sonography is a rapid, low cost and non-invasive method that may be useful to
      establish clinic diagnosis and in the first steps of gastric wall lesions
      evaluation, it is valuable in assessment of diagnostic orientation for the
      referring clinic.

PMID- 14712793
TI  - Does periodic vehicle inspection reduce car crash injury? Evidence from the
      Auckland Car Crash Injury Study.
AB  - OBJECTIVES: This paper examines the association between periodic motor vehicle
      inspection and frequent tire pressure checks, and the risk of car crash injury.
      METHODS: Data were analysed from the Auckland Car Crash Injury Study, a
      population-based case-control study in Auckland, NZ, where vehicles are required
      to undergo six-monthly safety inspections. Cases were all cars involved in
      crashes in which at least one occupant was hospitalised or killed, which
      represented 571 drivers. Controls were randomly selected cars on Auckland roads
      (588 drivers). Participants completed a structured interview. RESULTS: Vehicles
      that did not have a current certificate of inspection had significantly greater
      odds of being involved in a crash where someone was injured or killed compared
      with cars that had a current certificate, after adjustment for age, sex,
      marijuana use, ethnicity and licence type (OR 3.08, 95% CI 1.87-5.05). Vehicles
      that had not had their tire pressure checked within the past three months also
      had significantly greater odds of being involved in a crash compared with those
      that had a tire pressure check, after adjustment for age, sex, ethnicity,
      seatbelt use, licence type, self-reported speed and hours per week of driving
      exposure (OR 1.89, 95% CI 1.16-3.08). CONCLUSIONS: This study provides new
      evidence, using rigorous epidemiological methods and controlling for multiple
      confounding variables, of an association between periodic vehicle inspections and
      three-monthly tire pressure checks and reduced risk of car crash injury.
      DISCUSSION: This research suggests that vehicle inspection programs should be
      continued where they already exist and contributes evidence in support of
      introducing such programs to other areas.

PMID- 14712794
TI  - Statins may reduce risk for certain cancers.

PMID- 14712795
TI  - Device found to detect cancer painlessly.

PMID- 14712796
TI  - New treatment delivers chemotherapy directly to abdominal cancers.

PMID- 14712797
TI  - New drug found to reduce oral mucositis.

PMID- 14712798
TI  - How should diuretic-refractory, volume-overloaded heart failure patients be
      managed?

PMID- 14712800
TI  - [Abstracts of the 97th French Urology Congress. Paris, France, 19-22 November
      2003].

PMID- 14712801
TI  - CaixaForum. Abstracts of the 35th Annual General Meeting of the European Brain
      and Behaviour Society. 17-20 September 2003, Barcelona, Spain.

PMID- 14712799
TI  - Bivalirudin alone in the treatment of acute myocardial infarction.

PMID- 14712802
TI  - [Reports from the American Thoracic Society Annual Congress. Seattle, Washington,
      USA, 17-21 May 2003].

PMID- 14712803
TI  - [Ecos Internacionales. 14-16 August 2003, Mexico City, Mexico].

PMID- 14712805
TI  - Proceedings of the Occupational Skin Care Management State-of-the-Art Conference.
      September 1-3, 2000, Zurich, Switzerland.

PMID- 14712804
TI  - [53rd general meeting of the Japanese Society of Allergology. Gifu, Japan.
      October 23-25, 2003. Abstracts].

PMID- 14712806
TI  - [Abstracts of the XLVIX Congress of the French National Society of Internal
      Medicine. Grenoble, France, 11-13 December 2003].

PMID- 14712807
TI  - [Abstracts of the XXIII Congress of the Spanish Society of Family and Community
      Medicine. Barcelona, Spain, 10-13 December 2003].

PMID- 14712809
TI  - International Review of Neurobiology cumulative subject index, volumes 26-50.

PMID- 14712808
TI  - The welfare of zoo animals. Proceedings of the American Veterinary Medical
      Association Animal Welfare Forum. Milwaukee, Wisconsin, USA. October 11, 2002.

PMID- 14712810
TI  - Abstracts of the XXX National Congress of the Italian Society of Endocrinology.
      Milano, Italy, September 24-27, 2003.

PMID- 14712811
TI  - Abstracts from the 4th International Workshop on Adverse Drug Reactions and
      Lipodystrophy in HIV. San Diego, California, USA. September 22-25, 2002.

PMID- 14712812
TI  - References to contemporary papers on acoustics.

PMID- 14712814
TI  - International Review of Neurobiology cumulative subject index, volumes 1-25.

PMID- 14712813
TI  - Statement on the Scope and Standards of Medical Dosimetry Practice.
AB  - As healthcare delivery systems and technology continue to evolve, the role and
      responsibilities of the medical dosimetrist need to be delineated. The Scope and
      Standards of Medical Dosimetry Practice is design to provide a statement of
      competence in medical practice; define the practice of medical dosimetry; and
      provide a useful guide for medical dosimetrists and others in evaluating the
      quality, effectiveness, and appropriateness of health care services provided. In
      the process of developing the statement, the profession of medical dosimetry and
      credentialing are described; and a decision-making model to guide medical
      dosimetrists in determining scope of practice is provided.

PMID- 14712815
TI  - Abstracts from the International HIV Workshop on Management of Treatment
      Experienced Patients. San Diego, California, USA. September 26-27, 2002.

PMID- 14712816
TI  - Healthcare informatics 2004 resource guide.

PMID- 14712817
TI  - Abstracts of the XIth World Congress of Psychiatric Genetics. Quebec City,
      Canada, October 4-8, 2003.

PMID- 14712818
TI  - Piggies to market.

PMID- 14712819
TI  - Proceedings of the 2002 Meeting of the Society for the Study of Ingestive
      Behavior. Santa Cruz, California, USA. August 7-11, 2002.

PMID- 14712820
TI  - Stand and deliver.

PMID- 14712821
TI  - The LIS1-related protein NUDF of Aspergillus nidulans and its interaction partner
      NUDE bind directly to specific subunits of dynein and dynactin and to alpha- and
      gamma-tubulin.

PMID- 14712822
TI  - Revascularization using splenic artery to right gastroepiploic artery graft
      during total pancreatectomy after coronary arterial bypass grafting.

PMID- 14712824
TI  - [Abstracts of the XVIII Annual Meeting of Applied Research in Chagas Disease and
      the VI Annual Meeting of Applied Research in Leishmaniasis. Uberaba, Brazil, 17
      20 October 2002].

PMID- 14712823
TI  - Response to Zinberg's letter to the editor.

PMID- 14712825
TI  - Internet in Health for All. Mednet 2003. Abstracts of the 8th World Congress on
      the Internet in Medicine. Geneva, Switzerland, 4-7 December 2003.

PMID- 14712826
TI  - Abstracts of the 7th International Congress of the Polish Cardiac Society.
      September 11-13, 2003, Gdansk, Poland.

PMID- 14712827
TI  - Special Issue: Sublanguage. Dedicated to the memory of Zellig Harris.

PMID- 14712828
TI  - Abstracts of the AACR-NCI-EORTC International Conference: Molecular Targets and
      Cancer Therapeutics. November 17-21, 2003, Boston, Massachusetts, USA.

PMID- 14712829
TI  - Abstracts of the 12th Annual Meeting of the Israel Society for Neuroscience.
      Eliat, Israel, December 14-16, 2003.

PMID- 14712830
TI  - Cancer: "The worst scourge of civilized mankind".

PMID- 14712831
TI  - Patent news.

PMID- 14712832
TI  - Patent alert.

PMID- 14712833
TI  - The association of oxidative stress and inflammation in hemodialysis patients.

PMID- 14712834
TI  - Proteinuria and blood pressure instead of urine volume are risk factors for
      progression of renal disease.

PMID- 14712835
TI  - Abstracts of the XXI Annual Scientific Meeting of the Cuyo Biology Society, the
      10th Anniversary of Biocell, and the Foundation Meeting of the Argentine
      Microscopy Society. December 3-6, 2003. Mendoza, Argentina.

PMID- 14712836
TI  - [Abstracts of the German Orthopedic Congress. 13-16 November 2003, Berlin,
      Germany].

PMID- 14712837
TI  - [Abstracts of the 76th Meeting of the Rhein-Main Ophthalmologists Association. 1
      November 2003, Marburg].

PMID- 14712838
TI  - Educational attainment and risk of stroke and myocardial infarction.

PMID- 14712839
TI  - The whiplash odyssey.

PMID- 14712840
TI  - Purchasing & supply. Procure for all ills.

PMID- 14712841
TI  - Purchasing & supply. Under orders.

PMID- 14712842
TI  - Purchasing & supply. Hotel harmony. An alternative to taking the work in-house.

PMID- 14712843
TI  - Purchasing & supply. Tender is the price.

PMID- 14712844
TI  - Purchasing & supply. Chain reaction.

PMID- 14712845
TI  - Staff nurses' perceptions of the work environment in freestanding hemodialysis
      facilities.
AB  - While one suggested cause of the current nursing shortage is nurses' negative
      perceptions of the work environment, little is known of nephrology nurses'
      perceptions of the dialysis work environment. The purpose of this study was to
      assess the extent to which staff nurses who work in freestanding hemodialysis
      facilities rate the presence of organizational characteristics common to magnet
      hospitals in their current job. Study findings indicate that staff nurses in
      hemodialysis units identify several notable features of magnet hospitals in their
      work settings. However, a majority of nurses disagreed that many attributes of
      magnet hospitals are present in hemodialysis work environments. This study
      provides a preliminary description of some of the factors that affect nurses'
      perceptions of the work environment in freestanding dialysis facilities. Further
      work is needed in this area.

PMID- 14712846
TI  - [Pericarditis (acute)].

PMID- 14712847
TI  - What symptoms can tell about building-related causes.

PMID- 14712848
TI  - Eye irritation and environmental factors in the office environment--hypotheses,
      causes and a physiological model.
AB  - The study reviews eye irritation using a multidisciplinary approach. Potential
      risk factors and objective gender differences are identified, and possible
      hypotheses for eye irritation caused by indoor air pollution are discussed. Eye
      irritation depends somewhat on destabilization of the outer-eye tear film. An
      integrated physiological risk model with blink frequency, destabilization, and
      break-up of the eye tear film as inseparable phenomena may explain eye irritation
      among office workers in terms of occupational, climate, and eye-related
      physiological risk factors. Certain volatile organic compounds that are both
      chemically reactive and airway irritants may cause eye irritation. If airborne
      particles alone should destabilize the tear film and cause eye irritation, their
      content of surface-active compounds must be high. Personal factors (eg, use of
      contact lenses, eye make-up, and certain medication) may also affect
      destabilization of the tear film and possibly result in more eye symptoms.

PMID- 14712850
TI  - Does it help to know the work-relatedness of back pain in individual cases?

PMID- 14712849
TI  - Model for the work-relatedness of low-back pain.
AB  - OBJECTIVES: This study aimed at developing a model for determining the work
      relatedness of low-back pain for a worker with low-back pain using both a
      personal exposure profile for well-established risk factors and the probability
      of low-back pain if the worker were unexposed to these factors. METHODS: After a
      systematic review of the literature, the pooled prevalence of low-back pain in an
      unexposed population and the pooled odds ratio (OR) for each risk factor was
      calculated in a meta-analysis using a random effect model. An unbiased risk
      estimate for each risk factor was obtained by correcting the pooled OR for
      confounding by other risk factors. The probability of low-back pain was
      calculated with a logistic regression model. The input was (i) the age-dependent
      prevalence when not exposed and (ii) the unbiased risk estimates per risk factor
      of low and high exposure. The etiologic fraction was calculated to determine the
      level of work-relatedness. RESULTS: The pooled prevalence for low-back pain among
      unexposed subjects was 22%, 30%, and 34% for the <35-year, 35-to-45-year, and >45
      year age categories, respectively. The pooled OR was 1.51 [95% confidence
      interval (95% CI) 1.31-1.74] for manual materials handling, 1.68 (95% CI 1.41
      2.01) for frequent bending or twisting, 1.39 (95% CI 1.24-1.55) for whole-body
      vibration, and 1.30 (1.17-1.45) for job dissatisfaction. For high exposure to
      manual materials handling, frequent bending or twisting, and whole-body
      vibration, the pooled OR was 1.92, 1.93, and 1.63, respectively. CONCLUSIONS: The
      model is the first that estimates the probability of work-relatedness for low
      back pain for a given worker with low-back pain seen by a general practitioner or
      an occupational health physician.

PMID- 14712851
TI  - Where to with meta-analysis?--First, do no harm.

PMID- 14712852
TI  - Validity of a single-item measure of stress symptoms.
AB  - OBJECTIVES: The objective of the study was to investigate the content, criterion,
      and construct validity of a single-item measure of stress symptoms. Such a
      concise measure would be useful in monitoring stress at work. The criteria for
      validity were convergence with conceptionally close measures, the plausibility of
      associations with health and work characteristics, and the power to discriminate
      between groups. METHODS: Four sets of independent cross-sectional data were used.
      The first data set, from Finland Post, comprised symptoms of ill health and
      mental resources (N=1014). The second, from four Nordic countries, included well
      known validated scales on exhaustion, mental health, sleep, vitality, and
      optimism, and therefore the convergence between the measures could be studied
      (N=1015). The third, from a metal factory, included three indicators of health
      and four work characteristics (N=773). The fourth, representing the Finnish
      working population, described group differences in stress symptoms (N=2156) and
      allowed comparison with a study on emotional exhaustion in the working
      population. Distributions, correlations, and factor analysis were used for the
      study. RESULTS: The stress-symptoms item converged with items on psychological
      symptoms and sleep disturbances and with validated measures of well-being. It had
      theoretically grounded associations with indicators of health and psychosocial
      work characteristics, and it discriminated between gender and age groups and
      industrial branches in accordance with the validated emotional exhaustion scale.
      CONCLUSIONS: The stress-symptoms item showed satisfactory content, criterion, and
      construct validity for group-level analysis. It is suggested that the longer
      scales used to measure psychological stress can be replaced with it in survey
      research.

PMID- 14712853
TI  - Physiological responses to four hours of low-level repetitive work.
AB  - OBJECTIVES: The study investigated physiological responses to 4 hours of
      standardized low-level repetitive work. It was hypothesized that accumulative
      effects not observed after 1 hour could be found after 4 hours of repetitive
      work. METHODS: Ten healthy women performed intermittent (5 seconds + 5 seconds)
      handgrip contractions at 10% of the maximal voluntary contraction combined with
      mental demands for concentration and attention. Muscle activity in the working
      forearm muscles, cardiovascular responses, and concentrations of biomarkers in
      biological fluids were recorded along with exerted force, performance, and
      ratings of perceived physical exertion (RPE), and perceived mental exertion.
      RESULTS: The urinary epinephrine, norepinephrine, and cortisol concentrations
      were higher during the repetitive task than on a reference day, but only the
      norepinephrine concentrations increased progressively during the 4 hours. In
      accordance, the RPE recorded for the hand, forearm, and shoulder regions
      increased progressively. For the remaining physiological measures, no
      accumulative changes were found. Forearm muscle activity was higher during a
      mental reference task with lower exerted force than during the repetitive task.
      The variation in exerted force was higher during the repetitive task than during
      a force reference task without mental demands. CONCLUSIONS: The urinary
      biomarkers were increased during the repetitive task. However, only
      norepinephrine increased progressively during the 4 hours. Forearm muscle
      activity during a mental reference task with low exerted force indicated
      attention-related muscle activity. Finally, it was indicated that repetitive work
      including high demands for attention is performed at the expense of the precision
      of the exerted force.

PMID- 14712854
TI  - Nasal symptoms among residents in moldy housing.
AB  - OBJECTIVES: The aim of this study was to determine whether mold allergy mediated
      through immunoglobulin E (IgE) was responsible for the chronic nasal symptoms
      experienced by residents of moldy dwellings. A secondary aim was to investigate
      whether nasal mucosal findings were a possible reflection of other pathological
      mechanisms of chronic rhinitis. METHODS: Sixteen adults living in moldy housing
      and complaining of chronic rhinitis were compared with sixteen healthy referents
      without any known mold exposure. All the buildings were surveyed for visible
      signs of moisture and mold. Microbial measurements were performed in the damp
      buildings with mold problems and in half of the reference buildings. The clinical
      study consisted of an otorhinolaryngological examination, nasal cytology, and
      skin prick tests. In the study cases, nasal provocation tests with fungi cultured
      from the homes and nasal mucosal biopsy were performed. RESULTS: In the housing
      with signs of moisture and mold, the concentrations of microorganisms were
      elevated, but were within the normal range of those of the reference buildings.
      The only positive skin reaction for molds was detected in one referent. No
      reactions were elicited in the nasal provocation tests with molds. Squamous
      metaplasia were detected in four biopsies and three cytograms of the cases but
      not in the nasal smears of the referents. CONCLUSIONS: In this material, the
      respiratory symptoms reported by occupants of moldy residences were not caused by
      mold allergy but were apparently related to nonspecific inflammation following
      irritation.

PMID- 14712855
TI  - Work technique of nurses in patient transfer tasks and associations with personal
      factors.
AB  - OBJECTIVES: Back disorders among nursing personnel are associated with the
      worktask of assisting patients during transfers. The objectives of the study were
      to explore the work technique applied by nursing personnel in patient transfer
      tasks and to determine whether different personal factors were associated with
      work technique safety. METHODS: The work technique used by 102 nurses to perform
      two common patient transfer tasks in orthopedic wards, transfer higher up in bed
      and transfer from bed to wheelchair, was examined with the use of video
      recordings and an observation instrument. A work technique score was calculated
      for each performed transfer. It indicated the level of musculoskeletal safety and
      hazard for the nurse. The participants also filled out a questionnaire concerning
      different personal factors. RESULTS: A variety of strategies was used by the
      nurses to perform the transfer tasks. Being older and suffering from low-back
      symptoms were factors associated with the use of poor work technique in both
      tasks. There was also an association between male gender and poor technique in
      transferring patients from bed to wheelchair. CONCLUSIONS: The results indicate
      an association between poor work techniques and low-back symptoms. Special
      attention should be paid to older nurses, nurses with low-back problems, and
      possibly also to male nurses when training programs on patient transfer technique
      are designed, as these groups seem to apply comparatively poor work techniques in
      patient transfer tasks.

PMID- 14712856
TI  - Dutch practice guidelines for managing adjustment disorders in occupational and
      primary health care.
AB  - Stress-related disorders, especially adjustment disorders, are widespread among
      working populations and are responsible for high costs in terms of suffering,
      sick leave, disability, and economic losses. Despite their high prevalence, there
      has been relatively little research on the effectiveness of treatments in an
      occupational health care setting. Guidelines for occupational physicians and
      general practitioners in relation to mental health problems were recently
      developed in The Netherlands and are discussed in this article. The guidelines
      provide a classification based on terms that are already used in the profession
      and are consistent with the diagnosis "adjustment disorder". They give
      recommendations for guidance and treatment on the basis of existing evidence,
      experience in adjacent fields, and consensus procedures. They are based on
      cognitive behavioral principles, mainly stress inoculation training and graded
      activity, and aim to enhance the problem-solving capacity of patients in relation
      to the work environment. The aim of this paper is to contribute to the exchange
      of and a discussion on methods and good practices in primary and occupational
      health care.

PMID- 14712857
TI  - Health effects of reduced workhours?

PMID- 14712858
TI  - Behaviour of ring bivalents in holokinetic systems: alternative sites of spindle
      attachment in Pachylis argentinus and Nezara viridula (Heteroptera).
AB  - Heteropteran chromosomes are holokinetic; during mitosis, sister chromatids
      segregate parallel to each other but, during meiosis, kinetic activity is
      restricted to one pair of telomeric regions. This meiotic behaviour has been
      corroborated for all rod bivalents. For ring bivalents, we have previously
      proposed that one of the two chiasmata releases first, and a telokinetic activity
      is also achieved. In the present work we analyse the meiotic behaviour of ring
      bivalents in Pachylis argentinus (Coreidae) and Nezara viridula (Pentatomidae)
      and we describe for the first time the chromosome complement and male meiosis of
      the former (2n = 12 + 2m + X0, pre-reduction of the X). Both species possess a
      large chromosome pair with a secondary constriction which is a nucleolus
      organizer region as revealed by in-situ hybridization. Here we propose a new mode
      of segregation for ring bivalents: when the chromosome pair bears a secondary
      constriction, it is not essential that one of the chiasmata releases first since
      these regions or repetitive DNA sequences adjacent to them become functional as
      alternative sites for microtubule attachment and they undertake chromosome
      segregation to the poles during anaphase I.

PMID- 14712859
TI  - Comparative chromosome painting defines the karyotypic relationships among the
      domestic dog, Chinese raccoon dog and Japanese raccoon dog.
AB  - The Chinese raccoon dog (Nyctereutes procyonoides procyonoides, 2n = 54 + 2-3 B)
      and Japanese raccoon dog (Nyctereutes p. viverrinus, 2n = 38 + 3-4 B) are two
      subspecies of the same species. The genome-wide comparative chromosome map
      between the Japanese raccoon dog and domestic dog (Canis familiaris) has been
      established by fluorescence in-situ hybridization with a set of domestic dog
      painting probes. In this study, we established the comparative chromosome map for
      the Chinese raccoon dog and domestic dog. In total, dog probes specific for the
      38 autosomes delineated 41 conserved chromosomal segments in the Chinese raccoon
      dog. Probes from dog chromosomes 1, 13 and 19 each painted two Chinese raccoon
      dog chromosome segments. Fifteen dog autosomal probes each hybridized to one
      Chinese raccoon dog chromosome, while each of the other dog autosomal probes
      painted to a single Chinese raccoon dog chromosomal arm. Dog X chromosome probe
      delineated the entire X chromosome of the Chinese raccoon dog; the dog Y
      chromosome probe hybridized to the pseudoautosomal region at the Xpter as well as
      the entire Y chromosome of the Chinese raccoon dog. Comparative analysis of the
      distribution patterns of conserved segments defined by dog paints in the genomes
      of the Chinese and Japanese raccoon dogs demonstrates that their differences in
      the karyotypes of these two subspecies could have resulted from eight
      Robertsonian translocations. The large difference in chromosome number between
      the Chinese and Japanese raccoon dogs suggests that they should be considered as
      two distinct species.

PMID- 14712860
TI  - Characteristics and behaviour of the chromosomes of Leymus mollis and L.
      racemosus (Triticeae, Poaceae) during mitosis and meiosis.
AB  - Leymus mollis and L. racemosus (Triticeae; Poaceae) are important as genetic
      resources for wheat improvement, as they carry genes for salt tolerance and
      disease resistance. Even though these species share common Ns and Xm genomes, the
      genomic relationship between these two species is not yet clearly understood. In
      this study, we examined the genomes of the two species by FISH and GISH, using
      combinations of tandem-repetitive sequences and genomic DNAs. Comparative GISH
      showed that genomes in the genus Leymus were diverse. Nevertheless, chromosomes
      of these two species were able to undergo complete meiotic pairing in hybrids,
      suggesting that differences in the subtelomeric heterochromatin and sequences
      distinguishable by GISH do not affect meiotic pairing.

PMID- 14712861
TI  - Precise identification of chicken chromosomes in the lampbrush form using
      chromosome painting probes.
AB  - Chromosome painting probes specific for macrochromosomes 1, 2, 3, 4, 5, and Z
      were applied to both mitotic and lampbrush chromosomes of the chicken (Gallus
      gallus domesticus). Five autosomal macrobivalents and sex chromosome Z in the
      lampbrush phase were identified and their correspondence to the target
      chromosomes in the metaphase of mitosis was shown. Nascent transcripts on lateral
      loops of the target lampbrush chromosome were intensively labelled when the
      hybridization was performed without RNase A treatment according to the DNA/(DNA +
      RNA) hybridization protocol.

PMID- 14712862
TI  - Various organizations of the complex repeats in vole sex chromosome
      heterochromatin.
AB  - Different patterns of the DNA sequences organization were revealed in the vole
      (Rodentia) sex chromosome heterochromatin using dual-label fluorescence in-situ
      hybridization on extended DNA fibers with different repetitive DNA sequences as
      probes. In Microtus rossiaemeridionalis, the basic type represents the
      homogeneous relatively short tracks consisting of tandemly reiterated monomers of
      the MS3 family alternating with similar tracks of MS4 monomers and with non
      fluorescent spacers. These tracks varied in the length of both repeats, with an
      average size of 12-22 kb or 3-5 copies. Apart from this, some continuous tracks
      of both families spanning 100-200 kb were interrupted by short spacers or single
      signals from the sequences with homology to LINEs. These results, together with
      that obtained by the analysis of phage clones of the genomic library,
      unequivocally demonstrate a variable large-scale DNA structural organization in
      heterochromatin of the M. rossiaemeridionalis sex chromosome. The dominant type
      of large-scale DNA organization in M. transcaspicus heterochromatin represents
      the unicolor relatively long tracks consisting of monotonous but not alternating
      monomers of MS3 or MS4 with sizes ranging from 15 to 40 kb and separated by
      extended spacers with an average length of 20 kb. Thus, the formation of the vole
      sex chromosome heterochromatic regions occurred relatively recently during
      speciation.

PMID- 14712863
TI  - 'Signalling' between chromosomes in crane-fly spermatocytes studied using
      ultraviolet microbeam irradiation.
AB  - The present article deals with signals from kinetochores in anaphase crane-fly
      spermatocytes: when a half-bivalent's kinetochore is irradiated with an
      ultraviolet microbeam during anaphase, all half-bivalents in the cell stop moving
      to both poles. Movement blockage is temporary, and different half-bivalent pairs
      resume movement at different times. Movement stoppage presumably is due to
      signals arising from the irradiated kinetochores and transmitted to the 'motors'
      of the other chromosomes. We used a second irradiation (of the interzone) to
      determine the path of the signal. We reasoned that if irradiation of the
      interzone blocked transmission of the putative signal, then those chromosomes not
      receiving the signal should continue to move after irradiation of a kinetochore.
      Interzone irradiation interfered with the signal in about 20% of the 51 cells
      irradiated doubly, in that chromosome(s) moving to one pole stopped while
      chromosome(s) moving to the other pole continued. There was a second indication
      that interzonal irradiation blocked the signal: in about 30% of the cells in
      which the kinetochore was irradiated first and interzone second, all half
      bivalents resumed movement immediately after the second irradiation.

PMID- 14712864
TI  - DNA replication and transcription in new macronuclei of Paramecium caudatum
      exconjugants.
AB  - We analyzed the onset and location of replicational and transcriptional activity
      during the first cell cycle in new macronuclei of the ciliate Paramecium caudatum
      exconjugants. Synchronous exconjugants were pulse labeled with 5-bromo-2'
      deoxyuridine or 5-bromouridine-5'-triphosphate to visualize replication or
      transcription sites, respectively. The first morphological change after
      macronuclear determination is the appearance of heterochromatic aggregates.
      Confocal microscopic examination revealed that DNA replication started at the
      stage when new macronuclear chromatin was partially decondensed, and that
      replication sites were located in a large number of small spot-like areas
      excluding the heterochromatic regions. Transcriptional activation in the new
      macronuclei also took place in the same developmental stage and in the same
      region that replication started. As macronuclear development progressed,
      heterochromatic aggregates disappeared, and replication and transcription sites
      were scattered throughout the nucleoplasm. Moreover, studies on aphidicolin
      treated exconjugants demonstrated that inhibition of the DNA replication did not
      hinder transcriptional activation in the new macronuclei. On the other hand,
      replicational and transcriptional activity were also detected in old macronuclear
      fragments irrespective of their morphology and size, and length and timing of the
      replication corresponded to those in the new macronuclei.

PMID- 14712865
TI  - Dynamic relocation of telomere complexes in mouse meiotic chromosomes.
AB  - Telomeric DNA repeats as well as different specific proteins such as TRF1 and
      Rap1 associate in functional telomere complexes found at chromosome ends. Using
      spreading techniques, the presence of TRF1 and Rap1 has been reported at
      mammalian meiotic telomeres during prophase I. In the present study, we have
      analysed, by fluorescence in-situ hybridization and immunofluorescence, the
      appearance and location of telomere complexes during both male mouse meiotic
      divisions. Additionally, we have studied their relationship with different
      centromere/kinetochore proteins and the synaptonemal complex protein SCP3. Our
      results show that telomere complexes are not located at condensed meiotic
      chromosome tips. Therefore, a change in chromosome structure may occur from
      pachytene up to metaphase I involving the dynamic relocation of telomere
      complexes in condensed chromosomes. Moreover, we have found that proximal
      telomere complexes are relocated internally to kinetochores from metaphase I up
      to anaphase II. We discuss the functional significance of the location of
      telomere complexes into internal domains of condensed meiotic chromosomes.

PMID- 14712866
TI  - The da Vinci telerobotic surgical system: the virtual operative field and
      telepresence surgery.
AB  - The United States Department of Defense developed the telepresence surgery
      concept to meet battlefield demands. The da Vinci telerobotic surgery system
      evolved from these efforts. In this article, the authors describe the components
      of the da Vinci system and explain how the surgeon sits at a computer console,
      views a three-dimensional virtual operative field, and performs the operation by
      controlling robotic arms that hold the stereoscopic video telescope and surgical
      instruments that simulate hand motions with seven degrees of freedom. The three
      dimensional imaging and handlike motions of the system facilitate advanced
      minimally invasive thoracic, cardiac, and abdominal procedures. da Vinci has
      recently released a second generation of telerobots with four arms and will
      continue to meet the evolving challenges of surgery.

PMID- 14712867
TI  - The ZEUS robotic system: experimental and clinical applications.
AB  - Laparoscopic procedures provide shorter hospitalization, less pain, better
      cosmetic results, and faster returns to normal than traditional surgery. Surgeons
      performing them, however, are hampered by lack of tridimensional view and haptic
      sense, and by remoteness; but this physical gap also allows robotic and computer
      interfaces. The computer digitizes surgical movements and images and modifies
      this information to filter out nonfinalized movements such as tremor, increasing
      dexterity and precision. Digitized information can also be transmitted to remote
      locations, allowing surgical care in remote or underserved areas, and enhancing
      surgical education. There are several robotic surgical systems available; this
      article reviews the experimental and clinical use of the ZEUS robotic system and
      discusses its possible role in the future operating room.

PMID- 14712868
TI  - The Laprotek surgical system and the next generation of robotics.
AB  - The Brock Rogers Surgical Laprotek System is poised to extend the surgeon's reach
      into the future of advanced, minimally invasive procedures.

PMID- 14712869
TI  - Robotics and ergonomics.
AB  - Industrial robotics have proven the benefit of using an untiring machine to
      perform precise repetitive tasks in uncomfortable or dangerous for humans
      environments. Highly skilled surgeons are trained to operate and adapt to
      difficult conditions. They are even capable of developing intelligent mechanisms
      to exploit a variety of tactile, visual, and other cues. The robotic systems,
      however, can enhance the surgeon's capability to perform a wide variety of tasks.
      They cannot replace the surgeon's problem-solving ability. Instead, they will
      redefine his role. They will significantly enhance the surgeon's skills and
      dexterity by providing their complementary capabilities and an ergonomically
      efficient and more user-friendly working environment.

PMID- 14712870
TI  - Robotics and neurosurgery.
AB  - Ultimately, neurosurgery performed via a robotic interface will serve to improve
      the standard of a neurosurgeon's skills, thus making a good surgeon a better
      surgeon. In fact, computer and robotic instrumentation will become allies to the
      neurosurgeon through the use of these technologies in training, diagnostic, and
      surgical events. Nonetheless, these technologies are still in an early stage of
      development, and each device developed will entail its own set of challenges and
      limitations for use in clinical settings. The future operating room should be
      regarded as an integrated information system incorporating robotic surgical
      navigators and telecontrolled micromanipulators, with the capabilities of all
      principal neurosurgical concepts, sharing information, and under the control of a
      single person, the neurosurgeon. The eventual integration of robotic technology
      into mainstream clinical neurosurgery offers the promise of a future of safer,
      more accurate, and less invasive surgery that will result in improved patient
      outcome.

PMID- 14712871
TI  - Robotic cardiac surgery: overview.
AB  - Most endoscopic procedures are excisional, not reconstructive or microsurgical,
      mostly because conventional endoscopic instrumentation lacks dexterity due to
      long, nonarticulated instruments, a fixed pivot point and counterintuitive
      movement of the instrument tip, and lack of depth perception. Endoscopic
      approaches to cardiac surgery have not been successful; however, the development
      of robotic surgical systems has overcome many limitations of endoscopy. Computer
      assisted surgery has created a computerized digital interface between the
      surgeon's hands and surgical instrument tips and enhances surgical ability,
      thereby enabling endoscopic microsurgery. Recently, robotic systems have allowed
      cardiac surgeons to perform minimally invasive endoscopic coronary artery bypass
      grafting (CABG) and valve procedures. This article summarizes the use of robotics
      in cardiac surgery and discusses its potential in our specialty.

PMID- 14712872
TI  - Incorporating robotics into an open-heart program.
AB  - The above described clinical series show that after a careful and thorough
      training program and stepwise introduction of surgical telemanipulation systems,
      application of telemanipulations is safe and shows acceptable results. Still, OR
      times are longer than for conventional procedures, and the operation is
      demanding, and expensive. The main shortcoming is that the procedure is only
      suitable for a highly selected patient population. However, despite all the
      clinical experience gathered in various centers, this technique is still evolving
      and in its beginning. There are some very promising developments that will
      improve the benefit of telemanipulators. For the first time, the separation of
      the surgeon from the surgical field facilitates training of surgeons on
      simulators. This might lead to a higher standard of surgical performance.
      Progress in sensor technology will make tactile-force feedback available, and new
      3 D-visualization systems are designed to provide a better depth perception and
      higher resolution of the endoscopic image. Virtual stabilizing systems will
      enable robotic systems to operate on a virtual arrested heart without the need
      for CPB or mechanical stabilizers. These and other research topics summarized
      under the term augmented reality will enhance the natural senses and abilities of
      the surgeon. More and more, automatization will find its way into the OR.
      Preoperatively collected data about the patient's anatomy will be used to create
      safety margins, the robotic system will allow for the surgeon's movements, and
      instruments will be able to find their way to the surgical site without remote
      control. Because a stepwise approach has led to the clinical results that we and
      others have now achieved, it is the basis for further step-by-step development of
      the application of telemanipulation systems in coronary artery bypass grafting,
      and possibly other endoscopic procedures in cardiac surgery.

PMID- 14712873
TI  - Robotic coronary artery bypass grafting (CABG)--the Leipzig experience.
AB  - Technical and anatomical limitations as well as human factors complicate
      endoscopic coronary bypass surgery. Computer-enhanced telemanipulation systems
      overcome some of these shortcomings by restoring the dexterity and precision of a
      distant operator (surgeon) within a confined space. Endoscopic coronary artery
      bypass grafting (CABG) has evolved from a merely experimental approach to a
      clinical concept. Although CABG was initially exclusively performed on the
      arrested heart, adjunct technologies such as endoscopic vacuum-assisted
      stabilizers now allow a closed-chest, beating-heart procedure. The development of
      anastomotic devices, and further refinements in telemanipulator technology,
      optical systems, and image-guided augmented-reality scenarios will greatly
      facilitate endoscopic bypass grafting in the future.

PMID- 14712874
TI  - Robotic mitral valve surgery.
AB  - A renaissance in cardiac surgery has begun. The early clinical experience with
      computer-enhanced telemanipulation systems outlines the limitations of this
      approach despite some procedural success. Technologic advancements, such as the
      use of nitinol U-clips (Coalescent Surgical Inc., Sunnyvale, CA) instead of
      sutures requiring manual knot tying, have been shown to decrease operative times
      significantly. It is expected that with further refinements and development of
      adjunct technologies, the technique of computer-enhanced endoscopic cardiac
      surgery will evolve and may prove to be beneficial for many patients. Robotic
      technology has provided benefits to cardiac surgery. With improved optics and
      instrumentation, incisions are smaller. The ergometric movements and simulated
      three-dimensional optics project hand-eye coordination for the surgeon. The
      placement of the wristlike articulations at the end of the instruments moves the
      pivoting action to the plane of the mitral annulus. This improves dexterity in
      tight spaces and allows for ambidextrous suture placement. Sutures can be placed
      more accurately because of tremor filtration and high-resolution video
      magnification. Furthermore, the robotic system may have potential as an
      educational tool. In the near future, surgical vision and training systems might
      be able to model most surgical procedures through immersive technology. Thus, a
      "flight simulator" concept emerges where surgeons may be able to practice and
      perform the operation without a patient. Already, effective curricula for
      training teams in robotic surgery exist. Nevertheless, certain constraints
      continue to limit the advancement to a totally endoscopic computer-enhanced
      mitral valve operation. The current size of the instruments, intrathoracic
      instrument collisions, and extrathoracic "elbow" conflicts still can limit
      dexterity. When smaller instruments are developed, these restraints may be
      resolved. Furthermore, a working port incision is still required for placement of
      an atrial retractor, as well as needle, tissue, and suture retrieval. With the
      development of specialized retractors and a delivery/retrieval port, a truly
      endoscopic approach will be consistently reproducible. New navigation systems and
      image guided surgery portend an improving future for robotic cardiac surgery.
      Recently, we have combined robotically guided microwave catheters for ablation of
      atrial fibrillation with robotic mitral valve repairs (Fig. 8). Thus, we are
      beginning to achieve the ideal operation, with a native valve repair and a return
      to normal sinus rhythm. Robotic cardiac surgery is an evolutionary process, and
      even the greatest skeptics must concede that progress has been made toward
      endoscopic cardiac valve operations. Surgical scientists must continue to
      critically evaluate this technology in this new era of cardiac surgery. Despite
      enthusiasm, caution cannot be overemphasized. Surgeons must be careful because
      indices of operative safety, speed of recovery, level of discomfort, procedural
      cost, and long-term operative quality have yet to be defined. Traditional valve
      operations still enjoy long-term success with ever-decreasing morbidity and
      mortality, and remain our measure for comparison. Surgeons must remember that we
      are seeking the most durable operation with the least human trauma and quickest
      return to normalcy, all done at the lowest cost with the least risks. Although we
      have moved more asymptotically to these goals, surgeons alone must map the path
      for the final ascent.

PMID- 14712875
TI  - Robotics and general surgery.
AB  - Robotics are now being used in all surgical fields, including general surgery. By
      increasing intra-abdominal articulations while operating through small incisions,
      robotics are increasingly being used for a large number of visceral and solid
      organ operations, including those for the gallbladder, esophagus, stomach,
      intestines, colon, and rectum, as well as for the endocrine organs. Robotics and
      general surgery are blending for the first time in history and as a specialty
      field should continue to grow for many years to come. We continuously demand
      solutions to questions and limitations that are experienced in our daily work.
      Laparoscopy is laden with limitations such as fixed axis points at the trocar
      insertion sites, two-dimensional video monitors, limited dexterity at the
      instrument tips, lack of haptic sensation, and in some cases poor ergonomics. The
      creation of a surgical robot system with 3D visual capacity seems to deal with
      most of these limitations. Although some in the surgical community continue to
      test the feasibility of these surgical robots and to question the necessity of
      such an expensive venture, others are already postulating how to improve the next
      generation of telemanipulators, and in so doing are looking beyond today's
      horizon to find simpler solutions. As the robotic era enters the world of the
      general surgeon, more and more complex procedures will be able to be approached
      through small incisions. As technology catches up with our imaginations, robotic
      instruments (as opposed to robots) and 3D monitoring will become routine and
      continue to improve patient care by providing surgeons with the most precise,
      least traumatic ways of treating surgical disease.

PMID- 14712876
TI  - Telerobotic foregut and esophageal surgery.
AB  - Computer-assisted telerobotic surgery has many potential advantages over standard
      laparoscopy in foregut and esophageal surgery. The high-definition, three
      dimensional images produced by the optics of these systems can facilitate
      identification of anatomy and dissection during surgery. The full range of motion
      afforded by the multiarticulated instruments can be beneficial in completing
      complex laparoscopic tasks such as suturing and intracorporeal knot tying. Tremor
      filtration and motion scaling allows for more precise movements during surgery.
      The remote console provides the operating surgeon with a comfortable ergonomic
      position during the sometimes long and complex procedures. Despite the many
      advantages of these systems, however, several limitations still exist. It is
      expected that the development and refinement of these technologies will address
      many of these issues. With continued progress, it is likely that this technology
      will disseminate widely throughout the surgical community.

PMID- 14712877
TI  - Robot-assisted gastric surgery.
AB  - In conclusion, robot-assisted gastric surgery is now considered to be feasible in
      patients with Stage IA (T1N0) and Stage IB (T1N1, T2N0) early gastric cancer. The
      optimal treatment modalities have yet to be identified, however, and therefore
      clinical trials are called for. The authors believe that this new technology will
      markedly increase the survival rate of such patients all over the world in the
      near future, while also helping to significantly decrease the complication rates
      and hospital stay of the patients, which will thus result in a major beneficial
      socioeconomic impact.

PMID- 14712878
TI  - Robotic versus telerobotic laparoscopic cholecystectomy: duration of surgery and
      outcomes.
AB  - This study found that robotic and telerobotic operations were accomplished with
      the same mortality, morbidity, blood loss, length of operations and length of
      stay. The DaVinci operations required longer total operating room time than the
      AESOP operations. Telerobotic laparoscopic cholecystectomy achieved the same
      clinical outcomes as standard robotic laparoscopic cholecystectomy in this small
      trial. This study justifies further comparison of these techniques in a
      randomized prospective trial.

PMID- 14712879
TI  - Robot-assisted laparoscopic colorectal surgery.
AB  - Colorectal surgery can be difficult at open and laparoscopic surgery. This is
      particularly the case for rectal surgery deep in the pelvis. In obese males
      distal rectal dissection can be challenging because of instrument and visual
      limitations. Robot-assisted laparoscopic colorectal operations do not differ
      significantly from the standard laparoscopic approach but it has certainly been
      shown that it is feasible to perform the same operation using robotic assistance
      for the dissection. This allows the surgeon to benefit from vastly enhanced
      vision and dexterity, which may ultimately translate into benefit for the patient
      in terms of reduced operating time, and better preservation of pelvic nerves and
      other structures.

PMID- 14712880
TI  - Robotic renal and adrenal surgery.
AB  - Technology today is evolving at a dramatic rate. Quantum development has occurred
      in the area of robotic enhancement technology (RET) in the last decade.
      Incorporation of RET with advanced telecommunication technologies is a recent
      integration in medicine, with growth potential and application in the delivery of
      modern health care. There remain, however, many areas which need to be further
      improved and evaluated before clinical applications of the robot become accepted
      in adrenal and renal minimally invasive surgery.

PMID- 14712881
TI  - Robotics in gynecology.
AB  - The surgical robot has the potential to enable a laparoscopic approach to
      procedures that are presently performed by laparotomy due to the technical
      difficulties intrinsic to laparoscopy. The use of the current robot prototypes
      are not cost-effective for gynecologic procedures that are already performed by
      laparoscopy. The rapid evolution of robotics will likely allow for more
      widespread application in all surgical specialties in the future.

PMID- 14712882
TI  - Robotic surgery: from past to future--a personal journey.
AB  - A review of the history of robotic surgery--from its beginnings in a
      collaboration of engineers, computer scientists, and a plastic surgeon from
      Stanford Research Institute (SRI) and the NASA-Ames Research Center to the next
      generation of systems on the drawing board in the Department of Defense--provides
      a rich and colorful look at the author's participation in its development.
      Although Dr. Satava has participated in the development of other systems
      (orthopedic, ophthalmologic, and neurosurgical) that have contributed to the
      current distribution of robotic, computer-aided, and image-guided surgical
      systems, this article focuses on the development of the telemanipulation systems
      used for thoracic, abdominal, and pelvic surgery. Based upon emerging
      technologies, speculation is provided on the next generation of systems.

PMID- 14712883
TI  - Between the bombs.

PMID- 14712884
TI  - Efficacy and tolerability of formoterol Turbuhaler in children.
AB  - A randomised, double-blind trial was undertaken to investigate the efficacy and
      tolerability of formoterol Turbuhaler in children with mild to moderate asthma.
      After a two-week run-in, 248 children aged 6-17 years were randomised to receive
      formoterol 4.5 and 9 pmicro b.i.d. or placebo for 12 weeks. Morning PEF (primary
      variable), was significantly improved versus placebo only in the formoterol 9
      pmicro b.i.d. group (13 l/min, 95% CCI 1.9, 24.2%; p = 0 .02). Both formoterol
      4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2-6.7%
      (p < 0 .05) and reduced use of daytime relief medication versus placebo (p < 0
      .05). Formoterol 9 pmicro significantly reduced night-time reliever use and
      awakenings due to asthma versus placebo (p < 0.05). Both doses of formoterol were
      as well tolerated as placebo. In conclusion, formoterol 4.5 and 9 micro b.i.d. is
      effective and well tolerated as maintenance therapy in children with mild to
      moderate asthma.

PMID- 14712885
TI  - The effects of melatonin and prostaglandin E1 analogue on experimental hepatic
      ischaemia reperfusion damage.
AB  - The effects of antioxidant melatonin and a prostaglandin E1 analogue (PGE1) on
      hepatic ischaemia reperfusion damage were investigated. Fifty rats were divided
      into five equal groups: sham, control, melatonin, PGE1 and combined treatment. No
      procedures were applied to the sham group. In the control and treatment groups,
      the hepatic hilus was clamped at the level of the hepatic artery and portal vein
      for 60 min and reperfusion was provided for two hours. In the treatment and
      combined treatment groups, melatonin was administered intramuscularly at a dose
      of 20 mg/kg 15 mins before reperfusion, and PGE1 was administered intravenously
      at a dose of 25 mg/kg 1 min before reperfusion. Blood samples for SGOT, SGPT, GSH
      Px, SOD and MDA measurements and hepatic tissue samples were taken. The decrease
      in the plasma MDA levels was statistically significant in the melatonin and
      combined treatment groups, but not in the PGE1 group (p > 0.025). A significant
      decrease was found in the tissue MDA levels of the treatment groups (p < 0.025).
      The decrease in SGOT and SGPT levels in the PGE1 group was significant (p <
      0.025), but the decreases in the melatonin and combined treatment groups were not
      significant (p>0.025). Melatonin and PGE1 were found to be effective in reducing
      the hepatic ischaemia reperfusion damage in rats. However, the damage could not
      be reversed. Combined treatment was found not to be superior to melatonin or PGE1
      alone.

PMID- 14712886
TI  - The adjunctive effect of telmisartan in patients with hypertension uncontrolled
      on current antihypertensive therapy.
AB  - This prospective, double-blind, randomised, parallel-group, multicentre study
      assessed the adjunctive effect of telmisartan monotherapy versus placebo in
      controlling blood pressure during the last six hours of the 24-hour dosing
      period. After a two-week run-in phase, 375 patients with essential hypertension
      uncontrolled on existing therapy were randomised to either placebo or telmisartan
      (40 mg uptitrated to 80 mg after four weeks, if needed) for eight weeks.
      Ambulatory blood pressure monitoring (ABPM) was conducted at randomisation
      (baseline) and treatment end. The change from baseline in diastolic blood
      pressure (DBP) over the last six hours (primary endpoint) was significantly
      greater with telmisartan than placebo (adjusted mean treatment difference in
      favour of telmisartan: -3.7 mmHg, 95% confidence interval (CI) -5.5, -1.9 mmHg, p
      < or = 0.001, n = 350), as was the reduction in 24-hour DBP (adjusted mean
      treatment difference: -5.0 mmHg, 95% CI -6.5, -3.5 mmHg, p < or = 0.001).
      Telmisartan also reduced mean systolic blood pressure significantly more than
      placebo over the last six hours and the entire 24-hour dosing interval. Responder
      rates (ABPM DBP, seated DBP, and overall [seated SBP/DBP]) at 8 weeks were
      significantly higher with telmisartan than with placebo (p < or = 0.01). All
      treatments were well tolerated. When added to existing antihypertensive regimens,
      telmisartan offers additional effectiveness while maintaining placebo-like
      tolerability.

PMID- 14712887
TI  - Trimetazidine in geriatric patients with stable angina pectoris: the tiger study.
AB  - This study aims to assess the efficacy and tolerance of the metabolic antianginal
      agent trimetazidine, a 3-KAT inhibitor, in 141 stable angina patients aged 65-86
      years. Efficacy was assessed with exercise tests and clinical evaluation after 12
      weeks of treatment. The main outcome was an increase in exercise duration by 52
      +/- 92 sec (p < 0.001). Other exercise test parameters also improved, with no
      change in rate-pressure product. Angina attacks and short-acting nitrate
      consumption significantly decreased, indicating an improvement in quality of
      life. Two adverse events were reported (gastric pain and dyspepsia) but they were
      mild and transient. In conclusion, in elderly stable angina patients,
      trimetazidine improves exercise stress tests and angina symptoms. Because of its
      metabolic effect, free from any haemodynamic action, trimetazidine proved to be
      beneficial in elderly patients and with an excellent tolerance profile.

PMID- 14712888
TI  - Nasopharyngeal carcinoma in young patients.
AB  - Nasopharyngeal carcinoma (NPC) is rare in under 20-year-olds. Early diagnosis
      greatly improves survival. A retrospective review of 12 young NPC patients (seven
      males, five females, mean age 16 years) was performed to identify differing
      patient and tumour characteristics from adult NPC. Seventy-five per cent
      presented with neck lumps and 25% with headache. None had a family history of NPC
      or epistaxis. One patient had early stage NPC, and 11 had late stage NPC. Three
      late stage patients who received chemoradiotherapy had better clinical outcomes
      than six late stage patients receiving only radiotherapy. There were six deaths,
      five bony recurrences and one postnasal space recurrence. The 11 late stage
      patients' five-year actuarial survival was only 29%. Headache is an important
      symptom for young NPC. Late stage presentation and distant recurrences are also
      more common, supporting an increased role of chemotherapy.

PMID- 14712889
TI  - Efficacy and safety of brimonidine, dorzolamide and latanoprost as adjunctive
      therapy in primary open angle glaucoma.
AB  - A double-blind, randomised, controlled trial was carried out to evaluate the
      efficacy and safety of brimonidine, dorzolamide and latanoprost as an adjunctive
      therapy in patients with primary open angle glaucoma (POAG). A total of 200 males
      and 72 females with POAG uncontrolled with previous glaucoma therapy were
      randomly allocated to receive topical brimonidine 0.2% b.d. (n = 90), topical
      dorzolamide 2% b.d. (n=91) or topical latanoprost 0.005% o.d. (n = 91). One year
      post treatment, the mean percentage reduction in intraocular pressure (IOP)
      between the three groups was statistically significant (p < 0.0001). In an
      intergroup comparison of efficacy, there was a statistically significant
      difference between the brimonidine and dorzolamide groups (p = 0.018) and between
      the dorzolamide and latanoprost groups (p = 0.76) but the efficacy of brimonidine
      was not significantly higher than latanoprost in the brimonidine and latanoprost
      groups (p = 0.002). Patients experiencing mild to severe side-effects were
      statistically similar in the three groups. On an inter-drug comparison of side
      effects, we found no statistically significant difference in the brimonidine and
      latanoprost groups (p = 0.25); and the brimonidine and dorzolamide groups (p =
      0.067), while the number of side-effects with latanoprost was significantly
      higher in the dorzolamide and latanoprost groups (p<0.003). All three drugs
      caused a significant reduction in the mean IOP from pretreatment values. The
      brimonidine group had a higher number of patients experiencing severe side
      effects necessitating alteration of therapy.

PMID- 14712890
TI  - Clinicopathological and therapeutic patterns of idiopathic pulmonary fibrosis in
      Kuwait: a prospective study.
AB  - Though common, the exact incidence and clinical pattern of idiopathic pulmonary
      fibrosis (IPF) in Gulf countries are not known. The results of a four-year
      prospective study undertaken in two tertiary hospitals in Kuwait are presented.
      The mean age at diagnosis of the 52 patients studied was 55.40 +/- 11.87 years.
      Thirty-two (61.5%) patients were male and 22 (42.3%) were smokers. The mean
      duration of symptoms at diagnosis was 2.1 +/- 0.92 years. Digital clubbing was
      found in 34 (65%) patients. The mean FVC, TLC and TLCO were 57%, 64.4% and 55% of
      predicted normal, respectively. The FVC value showed a significant difference
      between smokers and non-smokers (p < 0.05). HRCT findings were abnormal in all
      patients. Typical histological and high-resolution computed tomography findings
      of usual interstitial pneumonia, desquamative interstitial pneumonia and non
      specific interstitial pneumonia were observed. This study revealed that IPF is
      prevalent in Kuwait, with patterns showing some similarities to those established
      elsewhere. The response to treatment was not encouraging, especially in the usual
      interstitial pneumonia subtype.

PMID- 14712891
TI  - Sarcomas of the breast.
AB  - Breast sarcomas are rare lesions that can be derived from any of the mammary
      stromal cells. A phyllodes tumour may resemble a rapidly growing fibroadenoma but
      in an older age group. Behaviour ranges from benign to frankly malignant and
      cannot always be predicted from the histological appearance. For all the sarcomas
      spread is haematogenous rather than lymphatic and treatment is based on wide
      surgical clearance without axillary surgery. Angiosarcoma is a rare consequence
      of skin irradiation as part of breast conservation therapy. Fibrosarcomas have a
      tendency to relapse locally unless wide surgical margins have been achieved.
      Radiotherapy is not of value but chemotherapy can be used to palliate women with
      metastatic disease.

PMID- 14712892
TI  - Enfuvirtide (Fuzeon): the first fusion inhibitor.
AB  - With the number of people living with HIV infection increasing and the problems
      of drug resistance and long-term toxicity associated with current antiretroviral
      agents continuing, there is a growing need for new therapy options. Enfuvirtide
      is the first fusion inhibitor, a new class of drug, to be licensed for the
      treatment of HIV infection and is a welcome addition to the arsenal of
      antiretrovirals. This paper, which is the result of a multidisciplinary
      discussion meeting, reviews current practice in treating HIV infection, the
      clinical data available on enfuvirtide and discusses its introduction into
      clinical practice. Data available to date indicate that enfuvirtide is
      appropriate for use in patients who have previously taken nucleoside reverse
      transcriptase inhibitor (NRTI), non-NRTI and protease inhibitor containing
      regimens and are either intolerant of them or have experienced virological
      failure. Enfuvirtide should ideally be used while the patient still has other
      active drug options available to them to combine with enfuvirtide in an effective
      therapy regimen.

PMID- 14712893
TI  - Antiplatelet drugs in cardiovascular diseases.
AB  - Platelets play a key role in the pathogenesis of atherothrombotic conditions,
      e.g. acute coronary syndromes, cerebrovascular and peripheral vascular events.
      Antiplatelet agents interfere with platelet activation and aggregation and, as
      such, would be expected to modify the natural history of cardiovascular disease.
      In this review we explore the evidence to support the use of such drugs, singly
      or in combination, in a variety of situations characterised by thrombosis and
      summarise some of the concerns inherent in their use.

PMID- 14712894
TI  - Tiotropium bromide: a long-acting anticholinergic bronchodilator for the
      treatment of patients with chronic obstructive pulmonary disease.
AB  - Prevention and relief of symptoms by regular use of bronchodilators is central to
      the management of patients with chronic obstructive pulmonary disease (COPD). The
      bronchodilators in use are beta2-agonists, anticholinergics and theophylline.
      Since the 1970s the anticholinergic ipratropium bromide has been widely used for
      the treatment of patients with regular symptoms, but because it has a relatively
      short duration of action, it needs to be administered four times a day.
      Tiotropium bromide is a long-acting anticholinergic suitable for once daily
      administration. It has been developed as a dry powder inhaler for the treatment
      of patients with COPD. Large clinical trials with administration of the drug for
      one year have now been published. Compared with placebo and ipratopium bromide,
      significant and long-lasting bronchodilatation was observed, which was maintained
      over the year. The bronchodilator effect of tiotropium bromide was accompanied by
      improvements in other health outcomes. A significant decrease in dyspnoea,
      improvement in health-related quality of life, and a reduction in the number of
      COPD exacerbations and hospitalisations were noted. In this review we summarise
      the clinical development of this compound.

PMID- 14712895
TI  - A rare complication of a prostatic stent.
AB  - We describe a case in which an elderly man with deteriorating lower urinary tract
      symptoms had problems with an indwelling prostatic stent. We discuss the merits
      of prostatic stents and recommend indications for their use.

PMID- 14712896
TI  - Testis-sparing surgery for benign and malignant testicular tumours.
AB  - We report the technique of testis-sparing surgery in three young men with
      testicular tumours, two of which were found to be benign (Leydig cell tumour and
      benign teratoma) and one malignant (seminoma) on frozen section and final
      pathological evaluation. The principles of clamping the spermatic cord with a
      soft bowel clamp, testicular cooling with ice slush, tumour enucleation with
      clear margins, meticulous haemostasis and frozen section analysis were followed.
      Testicular preservation was successful in the patients with benign disease. The
      patient with seminoma was found to have a separate nodule of invasive, poorly
      differentiated seminoma in the residual testis, which had not been detected on
      preoperative ultrasound scanning. As a result he was converted to radical
      orchidectomy.

PMID- 14712897
TI  - Bronchial entrapment of a chicken bone for 14 years.
AB  - Prolonged airway entrapment of a foreign body is a rare occurrence. We report a
      case of a chicken bone retained in the right main bronchus for 14 years and
      highlight the importance of a foreign body in the airway in the differential
      diagnosis of chronic and intractable cough.

PMID- 14712898
TI  - Isolated fatal renal mucormycosis in a patient with chronic obstructive pulmonary
      disease and tuberculosis.
AB  - Renal mucormyosis is a rare entity and normally diagnosed at postmortem. Isolated
      cases diagnosed antemortem are even rarer and only a few cases have been
      reported. The disease is associated with a high mortality rate, especially in
      patients with underlying disease. Clinical presentation is non-specific and
      includes flank pain, fever and pyuria with or without haematuria. Identifying
      fungal hyphae microscopically is essential for diagnosis. We present a rare
      isolated fatal case of renal mucormycosis in a 77-year-old man with chronic
      obstructive pulmonary disease (COPD) and old tuberculosis (TB) who had been
      diagnosed after a right nephrectomy. We believe early diagnosis and appropriate
      treatment for fungal infection, together with the predisposing underlying
      disease, is crucial for survival.

PMID- 14712899
TI  - Guillain-Barre syndrome associated with acute neurobrucellosis.
AB  - We report the case of a 14-year-old girl with Guillain-Barre syndrome associated
      with brucellosis due to Brucella melitensis. The diagnosis was established by the
      isolation of B. melitensis from her blood and by the determination of high levels
      of Brucella aglutinins in her sera and cerebrospinal fluid. A combination of
      rifampin, co-trimoxazole and physical therapy resulted in complete healing within
      30 days. Antibrucellar treatment continued for 12 weeks. This case report
      suggests that brucellosis should be kept in mind in the aetiology of Guillain
      Barre syndrome in the endemic areas for brucellosis, and bacteriological and
      serological tests for brucellosis should be performed.

PMID- 14712900
TI  - Hypertriglyceridaemia and NK cell lymphoma.
AB  - This case report describes a patient who presented with pyrexia of unknown origin
      allied with hypertriglyceridaemia (16.2 mmol/l) but not hypercholesterolaemia
      (4.1 mmol/l). Investigations identified the cause of the pyrexia as an adult T
      cell lymphoma of natural killer cell phenotype (CD3[+], CD7[+], anti-TCR
      alpha/beta[+], CD8[+], CD56[+]). Hypertriglyceridaemia has been reported with non
      Hodgkin s lymphoma, and an animal model suggests that antilipoprotein lipase
      antibodies may be made as an immunological response to the tumour. Lymphomas
      should be considered as part of the differential diagnosis in type IV-V
      hyperlipidaemia.

PMID- 14712901
TI  - Bilateral renal artery stenosis after abdominal radiotherapy for Hodgkin's
      disease.

PMID- 14712902
TI  - Lifting the lid on the 'black box' of multifaceted interventions to improve
      general practice performance.

PMID- 14712903
TI  - Information retrieval skills of researchers in general practice.

PMID- 14712904
TI  - Process evaluation of a multifaceted intervention to improve cardiovascular
      disease prevention in general practice.
AB  - OBJECTIVES: To perform a process evaluation of a multifaceted intervention to
      improve cardiovascular and diabetes care in general practice. METHODS: The
      feasibility of the intervention, carried out by outreach visitors in 62
      practices, was addressed by evaluating whether the intervention programme was
      performed as planned and the extent to which it was accepted by the practice
      team. In addition, the costs of the programme were determined. RESULTS: The
      intervention was largely carried out as planned, although the intervention period
      had to be extended by three months. Of the 18 topics that could be addressed
      during the intervention period, 12 (mean) were addressed. The number of outreach
      visits per practice was 15.2 (mean), each visit lasted about one hour. Most
      practice members endorsed both the key recommendations for clinical decision
      making and cardiovascular risk profiling. The majority of GPs (range 63-98%)
      agreed with the guidelines for clinical decision-making, and 29-97% had a
      positive opinion about the guidelines for practice organisation. According to
      practice staff members, the outreach visitor had sufficient knowledge and skills
      to support them in changing the practice organisation. GPs were less positive
      about the outreach visitor's knowledge and skills in optimising clinical decision
      making; however 78% believed that the outreach visitor contributed to effecting
      change in their clinical decision-making. The total costs of the intervention per
      practice were Euro 4317. CONCLUSIONS: This process evaluation demonstrated that
      the intervention was usually carried out as planned and achieved a high
      satisfaction rating from the participating practice members.

PMID- 14712905
TI  - Public knowledge, attitudes and behaviour regarding antibiotics--a survey of
      patients in general practice.
AB  - OBJECTIVE: To assess public knowledge, attitudes and behaviour regarding
      antibiotics to provide information for a local health education policy. DESIGN:
      Postal survey to 605 patients registered with two general medical practices in
      Grampian, North-East Scotland (351 respondents, 59.3%) in February/ March 2000.
      Questionnaire topics covered attitudes, knowledge and behaviour towards
      antibiotic use. RESULTS: 326 (93%) had experience of antibiotic use and 319 (81%)
      were happy to take antibiotics when necessary. 158 (45%) were concerned about
      antibiotic resistance. Few would expect antibiotics to treat a slight cold or
      heavy cold, but around half would expect antibiotics for very sore throats and
      influenza. 262 (75%) indicated they would ask a pharmacist for advice about the
      treatment of RTI. Most respondents experienced at least one episode of RTI during
      the review period. 280 (80%) provided details of their most recent episode; most
      self-treated, 57 consulted a doctor of whom 43 (75%) were prescribed antibiotics.
      CONCLUSIONS: Antibiotic resistance is a matter of concern for the public. Mixed
      opinions about the use of antibiotics for common respiratory tract infections
      were heard. Encouragingly the majority of people suffering an RTI during the
      review period treated themselves with paracetamol-based products for symptom
      relief. Those who consulted a doctor were in the minority but were likely to be
      prescribed antibiotics. Future local health education initiatives should target
      antibiotic use for sore throats as well as colds and 'flu.

PMID- 14712907
TI  - An evaluation of a handout on depression.

PMID- 14712906
TI  - Transient loss of consciousness with and without injuries: where to treat these
      patients?
AB  - OBJECTIVES: Transient loss of consciousness (LOC) is a fairly common phenomenon
      and frequently carries a risk of injury. The aim was to study the occurrence of
      injuries and causes of emergency referrals versus later specialist consultation
      in association with LOC in the primary healthcare setting. METHODS: A four-month
      survey was carried out in the Primary Healthcare Emergency Department of the City
      of Tampere, Finland (198,000 inhabitants). The subjects comprised consecutive
      patients aged at least 15 years, attending a primary healthcare emergency
      department because of LOC. The type of LOC was determined (seizure, syncope and
      uncertain) and the type and site of all injuries associated with LOC were
      registered. All referrals to hospital or specialist consultation because of LOC
      were also registered and the predictors of admission were analysed by logistic
      regression modelling. RESULTS: Injury was associated with 43 (20%) out of 220
      visits because of LOC; in 12/72 (17%) cases with syncope, in 24/118 (20%) with
      seizures and in 7/30 (23%) with an uncertain cause of LOC. Most of the injuries
      were minor. Emergency referral was required in 45/220 (20%) cases of LOC.
      Coronary heart disease and injury were the main predictors of emergency referral
      to hospital. CONCLUSIONS: Injuries are as frequent in patients with syncope as in
      those suffering seizures. Most patients with LOC in primary healthcare emergency
      departments do not seem to require emergency admission to hospital.

PMID- 14712908
TI  - In the jungle of information.

PMID- 14712909
TI  - Aspirin therapy in type 2 diabetes in a general practice in Italy.

PMID- 14712910
TI  - Influence of gender on the provision of palliative care.

PMID- 14712911
TI  - Will restructuring medical education and healthcare services in Turkey restore
      confidence in the PHC system?

PMID- 14712912
TI  - Non-rod, non-cone photoreception in rodents and teleost fish.
AB  - Until recently, all ocular photoreception was attributed to the rods and cones of
      the retina. However, studies on mice lacking rod and cone photoreceptors (rd/rd
      cl), has shown that these mice can still use their eyes to detect light to
      regulate their circadian rhythms, suppress pineal melatonin, modify locomotor
      activity and modulate pupil size. In addition, action spectra for some of these
      responses have characterized a novel opsin/vitamin A-based photopigment with a
      lambda(max) approximately 480 nm. Electrophysiological studies have shown that a
      subset of retinal ganglion cells are intrinsically photosensitive, and melanopsin
      has been proposed as the photopigment mediating these responses to light. In
      contrast to mammals, an inner retinal photopigment gene has been identified in
      teleost fish. Vertebrate ancient (VA) opsin forms a photopigment with a
      lambda(max) between 460-500 nm, and is expressed in a sub-set of retinal
      horizontal cells, and cells in the amacrine and ganglion cell layers.
      Electrophysiological analysis suggests that VA opsin horizontal cells are
      intrinsically photosensitive and encode irradiance information. In contrast to
      mammals, however, the function of these novel ocular photoreceptors remains
      unknown. We compare non-rod, non-cone ocular photoreceptors in mammals and fish,
      and examine the criteria used to place candidate photopigment molecules into a
      functional context.

PMID- 14712913
TI  - Cryptochromes and inner retinal non-visual irradiance detection.
AB  - Nearly all circadian clocks have free-running periods that differ significantly
      from 24 hours. To maintain synchrony with the 24 h day, the mammalian circadian
      clock is reset by light. Unlike other animals, mammalian circadian entrainment
      occurs exclusively via the eyes and optic nerves. Remarkably, the classical
      photoreceptors--the rods and cones--are not necessary for photic entrainment.
      Instead, a subset of inner retinal ganglion cells are directly photoresponsive
      and transmit photic information specifically to brain centres involved in
      irradiance detection, including the master circadian pacemaker in the
      suprachiasmatic nucleus of the hypothalamus. The photopigment(s) responsible for
      inner retinal phototransduction are unknown. Several lines of evidence constrain
      candidate photopigments. First, near-total vitamin A depletion does not diminish
      retinohypothalamic signalling. Second, loss of cryptochrome function in retinal
      degenerate mice substantially decreases photic signalling to the suprachiasmatic
      nucleus, and markedly decreases pupillary light responses. Third, vitamin A
      depletion of cryptochrome mutant mice leads to loss of photic signalling to the
      suprachiasmatic nucleus. These findings suggest a model where either classical
      photopigments or inner retinal photopigments are sufficient for non-visual
      irradiance detection.

PMID- 14712914
TI  - Light signalling in cryptochrome-deficient mice.
AB  - The mammalian master clock driving circadian rhythmicity in physiology,
      metabolism, and behaviour resides within the suprachiasmatic nuclei (SCN) of the
      anterior hypothalamus and is composed of intertwined negative and positive
      autoregulatory transcription-translation feedback loops. The Cryptochrome 1 and 2
      gene products act in the negative feedback loop and are indispensable for
      molecular core oscillator function, as evident from the arrhythmic wheel running
      behaviour and absence of cyclic clock gene expression in mCry1/mCry2 double
      mutant mice in constant darkness. Recently, we have measured real-time multi-unit
      electrode activity recordings in hypothalamic slices from mCry-deficient mice
      kept in constant darkness and observed a complete lack of circadian oscillations
      in firing patterns. This proves that CRY proteins, and thus an intact circadian
      clock, are prerequisite for circadian rhythmicity in membrane excitability in SCN
      neurons. Strikingly, when mCry-deficient mice are housed in normal light-dark
      cycles, a single non-circadian peak in neuronal activity can be detected in SCN
      slices prepared two hours after the beginning of the day. This light-induced
      increase in electric activity of the SCN suggests that deletion of the mCry genes
      converts the core oscillator in an hour-glass-like timekeeper and may explain why
      in normal day-night cycles mCry-deficient mice show apparently normal behaviour.

PMID- 14712915
TI  - Circadian light input in plants, flies and mammals.
AB  - The rotation of our planet results in daily changes in light and darkness, as
      well as seasons with characteristic photoperiods. Adaptation to these daily and
      seasonal changes in light properties (and associated changes in the environment)
      is important to the sustained survival of higher life forms on our planet. Many
      organisms use their intrinsic circadian oscillator or clock to orchestrate daily
      rhythms in behaviour and physiology to adapt to diurnal changes. Some higher
      organisms use the same oscillator to monitor day length in selecting the
      appropriate season for reproductive behaviour. Organisms have developed
      irradiance measurement mechanisms to ignore photic noise (lightning, moonlight),
      and use the light of dusk and dawn for circadian photoentrainment. They have also
      devised multiple photoreceptors and signalling cascades to buffer against changes
      in the spectral composition of natural light. The interaction of the clock with
      ambient light is, therefore, quite intricate.

PMID- 14712916
TI  - Orphan nuclear receptors, molecular clockwork, and the entrainment of peripheral
      oscillators.
AB  - Here we summarize our work on two aspects of circadian timing: the roles of
      orphan nuclear receptors in the molecular clockwork, and phase entrainment of
      peripheral oscillators. With reference to the former, studies on cis-acting
      regulatory elements within the Bmal1 promoter revealed that REV-ERBalpha, an
      orphan nuclear receptor provides a link between the positive and negative limbs
      of the molecular oscillator. Specifically, REV-ERBalpha controls the cyclic
      transcription of Bmal1 and Clock, the positive limb components. In turn, the
      circadian expression of Rev-Erbalpha itself is driven directly by the molecular
      oscillator: it is activated by BMAL1 and CLOCK, and repressed by PERIOD1/2 and
      CRYPTOCHROME1/2 proteins (the negative limb members). With regard to phase
      entrainment, it was initially believed that only the suprachiasmatic nucleus
      (SCN) was capable of generating circadian rhythms. However, circadian oscillators
      have recently been discovered in many peripheral tissues. In the absence of a
      functional SCN pacemaker, these peripheral clocks dampen after a few days. Hence,
      the SCN must periodically synchronize these subsidiary timekeepers. It may
      accomplish this task mostly through an indirect route: namely, by setting the
      time of feeding. In addition to feeding cycles, body temperature rhythms and
      cyclically secreted hormones might also serve as zeitgebers for peripheral
      clocks.

PMID- 14712917
TI  - SCN: ringmaster of the circadian circus or conductor of the circadian orchestra?
AB  - The mammalian circadian system is composed of multiple circadian oscillators in
      both the brain and the periphery. Unravelling the organization of this system is
      a major challenge that the field is only beginning to take on. Clearly the
      suprachiasmatic nucleus of the hypothalamus (SCN) plays a key role and sits at or
      near the top of the organizational hierarchy, the details of which are largely
      unknown. The SCN has often been characterized as a 'master oscillator' that
      controls other oscillators downstream in the hierarchy, but there is little
      information about the nature of that control or how rigid or flexible it may be.
      Indeed, characterization of the SCN as 'master' may be exaggerated since other
      central circadian pacemakers are known to exist and the extent of feedback onto
      the SCN from other oscillators remains unexplored. We have tried to make some of
      the issues concerning the role of the SCN within the entire system more explicit
      using the somewhat fanciful metaphor referred to in the title.

PMID- 14712918
TI  - On the communication pathways between the central pacemaker and peripheral
      oscillators.
AB  - Circadian rhythms are regulated by clocks located in specific structures of the
      CNS, such as the suprachiasmatic nucleus (SCN) in mammals, and by peripheral
      oscillators present in various other tissues. The expression of essential clock
      genes oscillates both in the SCN and in peripheral pacemakers. Peripheral tissues
      in the fly and in the fish are directly photoreceptive. In particular, we have
      established the Z3 embryonic zebrafish cell line that recapitulates the dynamic
      light-dependent regulation of the vertebrate clock in vitro. In mammals the
      synchronization to daily light cycles involves neural connections from a subset
      of light-sensitive receptor-containing retinal ganglion cells. Humoral and/or
      hormonal signals originating from the SCN are thought to provide timing cues to
      peripheral clocks. However, alternative routes exist, as some peripheral clocks
      in mammals can be specifically entrained in a SCN-independent manner by
      restricted feeding regimes. Thus, not all peripheral tissues are equal in
      circadian rhythmicity. Testis, for example, displays no intrinsic circadian
      rhythmicity and the molecular mechanisms of clock gene activation in male germ
      cells appear to differ from other tissues. The study of the connecting routes
      that link the SCN to peripheral tissues is likely to reveal signalling pathways
      of fundamental physiological significance.

PMID- 14712919
TI  - Central and peripheral circadian oscillators in Drosophila.
AB  - Drosophila circadian oscillators comprise interlocked period (per)/timeless (tim)
      and Clock (Clk) transcriptional/translational feedback loops. Within these
      feedback loops, CLOCK (CLK) and CYCLE (CYC) bind E-box elements to activate per
      and tim transcription, and we now show that at the same time CLK-CYC repress Clk
      by activating the transcriptional repressor vrille (vri), thus accounting for the
      opposite cycling phases of these transcripts and identifying vri as the negative
      component of the Clk-feedback-loop. The core oscillator mechanism is assumed to
      be the same for oscillators in different tissues. However, we have shown that
      CRYPTOCHROME (CRY) has a light-independent function in the oscillator that
      controls olfaction rhythms, suggesting that CRY may function within the
      oscillator mechanism itself as it does in mammals. These olfaction rhythms
      require the function of 'peripheral' oscillators which are distinct from the
      'central' lateral neuron (LN) oscillators that mediate locomotor activity
      rhythms. Preliminary results show that antennal oscillator cells are sufficient
      and LNs are not necessary for olfaction rhythms, indicating that unlike the
      situation in mammals, the central oscillator has little impact on the olfaction
      rhythm oscillator under these conditions.

PMID- 14712920
TI  - Integration of molecular rhythms in the mammalian circadian system.
AB  - The discovery of clock genes and the general principles of their oscillation have
      made research on biological clocks a highly interesting field in the life
      sciences. As in other species, the mammalian circadian core oscillator is thought
      to be composed of an autoregulatory transcription-(post)translation-based
      feedback loop involving a set of clock genes. The production, phosphorylation,
      ubiquitination and proteasome-dependent degradation of clock proteins has a key
      role in generating the clock oscillation. The generation of internal clock time
      occurs in the hypothalamic suprachiasmatic nucleus (SCN), where clock gene
      oscillation in each neuron is coupled and amplified. These well synchronized
      oscillatory signals are spread into the whole brain and to peripheral organs
      which contain peripheral clocks. The important feature of the circadian system is
      that the rhythm of gene transcription of dock genes in the SCN reflects the
      behavioural rhythm almost perfectly. Investigations on biological clocks present
      the fascinating prospect of analysing the integrational mechanism of 'time' from
      genes to the living organism.

PMID- 14712921
TI  - Circadian transcriptional output in the SCN and liver of the mouse.
AB  - Circadian oscillators orchestrate daily rhythms in behaviour and physiology to
      adapt to the predictable daily appearance of light. Identifying the complement of
      circadian-regulated transcripts in major organs is critical in the understanding
      of both the biochemical targets of clock regulation and the mechanism of such
      control. Recent analysis of temporal gene expression patterns in peripheral and
      central oscillators have revealed hundreds of circadian-regulated transcripts,
      most of which are tissue-specific. Mapping of these transcripts to physiological
      processes and pathways has revealed that major functions of those organs tested
      are under circadian regulation, and importantly, key and rate-limiting steps in
      these processes are often the targets of circadian control. Overall, nearly 100%
      of the mammalian genome may be regulated by the clock, demonstrating the
      pervasive control of the circadian oscillator in temporal coordination of
      transcription throughout the organism. This wealth of circadian outputs offers
      exciting challenges to deciphering systems-level transcriptional regulatory
      mechanisms that underlie spatiotemporal gene expression.

PMID- 14712922
TI  - The molecular workings of the Neurospora biological clock.
AB  - In Neurosporacrassa the FRQ/WC feedback loop has been shown to be central to the
      function of the circadian clock. Similar to other eukaryotic systems it is based
      on a transcription-translation PAS heterodimer type feedback. FRQ levels cycle
      with a period identical to that of the Neurospora circadian cycle and its
      expression is rapidly induced by light. A complex of White Collar 1 (WC-1) and
      White Collar 2 (WC-2) (the WCC) is required for the transcriptional activation of
      frq. The oscillation in frq message is transcriptionally regulated via a single
      necessary and sufficient cis-acting element in the frq promoter, the Clock-Box
      (CB) bound by WCC. Light-induction of frq transcription is mediated by WCC
      binding to two cis-acting elements (LREs) in the frq promoter. WC-1, with flavin
      adenine dinucleotide (FAD) as a cofactor, is the blue-light photoreceptor. The
      original description of a frq-null strain, frq9, (Loros et al 1986) included a
      description of oscillations in asexual conidial banding that occasionally
      appeared following 3 to 7 days of arrhythmic development now referred to as FLO
      for FRQ-less oscillator. Unlike the intact clock, FLO period is sensitive to
      media composition. We have identified a circadianly regulated gene whose mutation
      interferes with FLO even under temperature entrainment conditions. This same
      mutation affects the circadian clock in a frq+ background causing a shorter
      period length as well as temperature response defects. This gene may be an entry
      point to study the connection between the biological clock and other basic
      cellular mechanisms.

PMID- 14712923
TI  - Expression of clock gene products in the suprachiasmatic nucleus in relation to
      circadian behaviour.
AB  - Circadian timing within the suprachiasmatic nucleus (SCN) is modelled around cell
      autonomous, autoregulatory transcriptional/post-translational feedback loops, in
      which protein products of canonical clock genes Period and Cryptochrome
      periodically oppose transcription driven by CLOCK:BMAL complexes. Consistent with
      this model, mCLOCK is a nuclear antigen constitutively expressed in mouse SCN,
      whereas nuclear mPER and mCRY are expressed rhythmically. Peaking in late
      subjective day, mPER and mCRY form heteromeric complexes with mCLOCK, completing
      the negative feedback loop as levels of mPer and mCry mRNA decline. Circadian
      resetting by light or non-photic resetting (mediated by neuropeptide Y) involves
      acute up- and down-regulation of mPer mRNA, respectively. Expression of Per mRNA
      also peaks in subjective day in the SCN of the ground squirrel, indicating common
      clock and entrainment mechanisms for nocturnal and diurnal species. Oscillation
      within the SCN is dependent on intercellular signals, in so far as genetic
      ablation of the VPAC2 receptor for vasoactive intestinal polypeptide (VIP)
      suspends SCN circadian gene expression. The pervasive effect of the SCN on
      peripheral physiology is underscored by cDNA microarray analysis of the circadian
      gene expression in liver, which involves ca. 10% of the genome and almost all
      aspects of cell function. Moreover, the same molecular regulatory mechanisms
      driving the SCN appear also to underpin peripheral cycles.

PMID- 14712924
TI  - Circadian rhythms in Drosophila.
AB  - We discuss some historical features of the circadian in Drosophila melanogaster.
      We then describe some recent progress from our laboratory in three different
      areas. First, we discuss the regulation of circadian gene expression as assayed
      with microarrays. Results are discussed that verify and extend published data,
      both with respect to the previously identified cycling mRNAs as well as some
      clustering within the genome of some of the genes that give rise to these
      circadian transcripts. Also discussed are experiments that attempt to identify
      transcripts that are enriched in lateral neurons, the key circadian pacemaker
      cells in the Drosophila brain. Second, the issue of damping within the brain is
      addressed, by assaying molecular oscillations after many days in constant
      darkness. Third, the identification of a new circadian mutant is described, which
      is a fully recessive allele of the gene Clock. The previous allele in flies, as
      well as the single mutant allele in mice, is a dominant allele. This limits the
      conclusions that can be drawn from the genetic and molecular analyses in these
      mutant strains. Results with the new recessive allele not only support the notion
      that Clock is an important clock gene but also indicate that it contributes more
      to the amplitude of the rhythm rather than the period.

PMID- 14712925
TI  - The role of phosphorylation and degradation of hPER protein oscillation in normal
      human fibroblasts.
AB  - The circadian expression in Drosophila of clock gene products, such as PER and
      TIM, is thought to be important for driving overt rhythms. The constitutive
      expression of per by the heat-shock or rhodopsin promoters restores rhythmicity
      of the null allele of per, suggesting that per mRNA cycling may not be required
      for protein cycling or for locomotor rhythms. Furthermore, the constitutive
      expression of tim mRNA also supports protein cycling and behavioural rhythms in
      tim mutant flies. Other reports have also shown that eliminating the oscillations
      of PER and TIM proteins by their over-expression abrogated circadian rhythmicity.
      These data indicate that the circadian rhythmic expression of PER and TIM
      proteins is also important like their rhythmic mRNA expression in Drosophila. To
      compare the molecular mechanism of circadian clocks in divergent species, we
      report here cloning circadian mRNA and protein expression profiling of human
      clock genes in normal human fibroblasts. Circadian oscillations of hPer1, hPer2,
      hPer3, hBMAL1 and hCry2 mRNA expression were observed in serum-stimulated normal
      human fibroblasts. The serum shock of human fibroblasts also caused daily
      oscillations in the amount and size of human PER proteins as was shown using our
      novel antibodies. Inhibitor studies indicate that phosphorylation and degradation
      of PER proteins is an important process in the human molecular clock.

PMID- 14712926
TI  - Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor
      signalling.
AB  - The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive
      daily rhythms of behaviour by secreting factors that act locally within the
      hypothalamus. In a systematic screen, we identified transforming growth factor
      (TGF)alpha as a likely SCN inhibitor of locomotion. TGFalpha is expressed
      rhythmically in the SCN, and when infused into the 3rd ventricle it reversibly
      inhibits locomotor activity and disrupts circadian sleep-wake cycles. These
      actions are mediated by epidermal growth factor (EGF) receptors, which we
      identified on neurons in the hypothalamic subparaventricular zone. Mice with a
      hypomorphic EGF receptor mutation exhibit excessive daytime locomotor activity
      and fail to suppress activity when exposed to light. These results implicate EGF
      receptor signalling in the daily control of locomotor activity, and they identify
      a neural circuit in the hypothalamus that likely mediates the regulation of
      behaviour both by the SCN and the retina.

PMID- 14712927
TI  - CK1 and GSK3 in the Drosophila and mammalian circadian clock.
AB  - Two kinases, DOUBLETIME and SHAGGY, have been shown to play a role in the
      circadian clock. DOUBLETIME, the Drosophila orthologue of casein kinase 1, can
      phosphorylate PERIOD in the cytoplasm and in the nucleus. This phosphorylation
      destabilizes PERIOD in both locations and sets patterns of both cytoplasmic
      accumulation and nuclear turnover. Cytoplasmic phosphorylation postpones
      accumulation of PERIOD and affects timing of nuclear accumulation of PERIOD/
      TIMELESS complexes. SHAGGY, the Drosophila orthologue of glycogen synthase kinase
      3, phosphorylates TIMELESS and promotes nuclear translocation of PERIOD/ TIMELESS
      complexes. Thus, the opposing effects of these two kinases in the cytoplasm are
      crucial for establishing the approximately 24 h period of circadian rhythmicity
      in Drosophila. Casein Kinase 1 has been shown to be a component of the circadian
      clock in mammals. Recent studies are also pointing to a role for glycogen
      synthase kinase 3 in the mammalian clock.

PMID- 14712928
TI  - Immunoinformatics: bioinformatic strategies for better understanding of immune
      function. Introduction.

PMID- 14712929
TI  - Immunoinformatics--the new kid in town.
AB  - The astounding diversity of immune system components (e.g. immunoglobulins,
      lymphocyte receptors, or cytokines) together with the complexity of the
      regulatory pathways and network-type interactions makes im munology a
      combinatorial science. Currently available data represent only a tiny fraction of
      possible situations and data continues to accrue at an exponential rate.
      Computational analysis has therefore become an essential element of immunology
      research with a main role of immunoinformatics being the management and analysis
      of immunological data. More advanced analyses of the immune system using
      computational models typically involve conversion of an immunological question to
      a computational problem, followed by solving of the computational problem and
      translation of these results into biologically meaningful answers. Major
      immunoinformatics developments include immunological databases, sequence
      analysis, structure modelling, mathematical modelling of the immune system,
      simulation of laboratory experiments, statistical support for immunological
      experimentation and immunogenomics. In this paper we describe the status and
      challenges within these sub-fields. We foresee the emergence of immunomics not
      only as a collective endeavour by researchers to decipher the sequences of T cell
      receptors, immunoglobulins, and other immune receptors, but also to functionally
      annotate the capacity of the immune system to interact with the whole array of
      selfand non-self entities, including genome-to-genome interactions.

PMID- 14712930
TI  - The future for computational modelling and prediction systems in clinical
      immunology.
AB  - Advances in computational science, despite their enormous potential, have been
      surprisingly slow to impact on clinical practice. This paper examines the
      potential of bioinformatics to advance clinical immunology across a number of key
      examples including the use of computational immunology to improve renal
      transplantation outcomes, identify novel genes involved in immunological
      disorders, decipher the relationship between antigen presentation pathways and
      human disease, and predict allergenicity. These examples demonstrate the enormous
      potential for immunoinformatics to advance clinical and experimental immunology.
      The acceptance of immunoinformatic techniques by clinical and research
      immunologists will need robust standards of data quality, system integrity and
      properly validated immunoinformatic systems. Such validation, at a minimum, will
      require appropriately designed clinical studies conducted according to Good
      Clinical Practice standards. This strategy will enable immunoinformatics to
      achieve its full potential to advance and shape clinical immunology in the
      future.

PMID- 14712931
TI  - Immunoinformatics in personalized medicine.
AB  - Diagnosis of human disease has been undergoing steady improvement over the past
      few centuries. Many ailments that were once considered a single entity have been
      classified into finer categories on the basis of response to therapy (e.g. type I
      and type II diabetes), inheritance (e.g. familial and non-familial polyposis
      coli), histology (e.g. small cell and adenocarcinoma of lung) and most recently
      transcriptional profiling (e.g. leukaemia, lymphoma). The next dimension in this
      finer categorization appears to be the typing of the patient rather than the
      disease i.e. disease X in person of type Y. The problem of personalized medicine
      is to devise tests which predict the type of individual, especially where the
      type is correlated with response to therapy. Immunology has been at the forefront
      of personalized medicine for quite a while, even though the term is not often
      used in this connection. Blood grouping and cross-matching (for blood
      transfusion), and anaphylaxis test (for penicillin) are just two examples. In
      this paper I will argue that immunological tests have an important place in the
      future of personalized medicine. I will describe methods we developed for
      personalizing vaccines based on MHC allele frequencies in human populations and
      methods for predicting peptide binding to class I MHC molecules. In conclusion, I
      will argue that immunological tests, and consequently immunoinformatics, will
      play a big role in making personalized medicine a reality.

PMID- 14712932
TI  - From immunome to vaccine: epitope mapping and vaccine design tools.
AB  - Since the publication of the complete genome of a pathogenic bacterium in 1995,
      more than 50 bacterial pathogens have been sequenced and at least 120 additional
      projects are currently underway. Faced with the expanding volume of information
      now available from genome databases, vaccinologists are turning to epitope
      mapping tools to screen vaccine candidates. Bioinformatics tools such as
      EpiMatrix and Conservatrix, which search for unique or multi-HLA-restricted
      (promiscuous) T cell epitopes and can find epitopes that are conserved across
      variant strains of the same pathogen, have accelerated the process of epitope
      mapping. Additional tools for screening epitopes for similarity to 'self'
      (BlastiMer) and for assembling putative epitopes into strings if they overlap
      (EpiAssembler) have been developed at EpiVax. Tools that map proteasome cleavage
      sires are available on the Internet. When used together, these bioinformatics
      tools offer a significant advantage over traditional methods of vaccine design
      since high throughput screening and design is performed in silico, followed by
      confirmatory studies in vitro. These new tools are being used to develop novel
      vaccines and therapeutics for the prevention and treatment of infectious diseases
      such as HIV, hepatitis C, tuberculosis, and some cancers. More recent
      applications of the tools involve deriving novel vaccine candidates directly from
      whole genomes, an approach that has been named 'genome to vaccine'.

PMID- 14712933
TI  - Insights from MHC-bound peptides.
AB  - Cytotoxic T cells recognize short antigenic peptides, the processing products of
      protein antigens, when they are bound to major histocompatibility complex (MHC)
      class I molecules. Peptide binding to MHC molecules has been studied extensively
      in numerous laboratories, providing vast amounts of sequence and structure data
      that have been used as a rich source for bioinformatic research. MHC-bound
      peptides and their flanking sequences provide information about the sequence
      requirements of the different processing stages, in particular, the cleavage by
      the proteasome and the binding to MHC molecules. Elucidation of these sequence
      requirements sheds light on the evolutionary forces that have shaped and designed
      these peptides, and should lead to the development of an integrative predictive
      algorithm. Remarkably, the peptide sequence and structure data are also valuable
      for the study of biological questions that are apparently unrelated to cellular
      immunity, namely, sequence-structure relationship and genome annotation. Here we
      describe our computational analyses of MHC-bound peptides, applied to all these
      biological topics.

PMID- 14712934
TI  - Computational vaccinology: quantitative approaches.
AB  - The immune system is hierarchical and has many levels, exhibiting much emergent
      behaviour. However, at its heart are molecular recognition events that are
      indistinguishable from other types of biomacromolecular interaction. These can be
      addressed well by quantitative experimental and theoretical biophysical
      techniques, and particularly by methods from drug design. We review here our
      approach to computational immunovaccinology. In particular, we describe the
      JenPep database and two new techniques for T cell epitope prediction. One is
      based on quantitative structure-activity relationships (a 3D-QSAR method based on
      CoMSIA and another 2D method based on the Free-Wilson approach) and the other on
      atomistic molecular dynamic simulations using high performance computing. JenPep
      (http://www.jenner.ar.uk/ JenPep) is a relational database system supporting
      quantitative data on peptide binding to major histocompatibility complexes, TAP
      transporters, TCR-pMHC complexes, and an annotated list of B cell and T cell
      epitopes. Our 2D-QSAR method factors the contribution to peptide binding from
      individual amino acids as well as 1-2 and 1-3 residue interactions. In the 3D
      QSAR approach, the influence of five physicochemical properties (volume,
      electrostatic potential, hydrophobicity, hydrogen-bond donor and acceptor
      abilities) on peptide affinity were considered. Both methods are exemplified
      through their application to the well-studied problem of peptide binding to the
      human class I MHC molecule HLA-A*0201.

PMID- 14712935
TI  - IMGT, the international ImMunoGeneTics information system, http://imgt.cines.fr.
AB  - IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr),
      is a high quality integrated knowledge resource specializing in immunoglobulins
      (IG), T cell receptors (TR) and major histocompatibility complexes (MHC) and
      related proteins of the immune system (RPI) of human and other vertebrates,
      created in 1989 by LIGM at the Universite Montpellier II, CNRS, Montpellier,
      France. IMGT provides a common access to standardized data which include
      nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic
      polymorphisms, specificities, and 2D and 3D structures. IMGT includes five
      databases (IMGT/LIGM-DB, IMGT/3Dstructure-DB, IMGT/MHC-DB, IMGT/PRIMER-DB,
      IMGT/GENE-DB) Web resources ('IMGT Marie-Paule page') and interactive tools
      (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/PhyloGene, IMGT/LocusView,
      IMGT/GeneView, IMGT/GeneSearch, IMGT/StructureQuery). IMGT data are expertly
      annotated according to the rules of the IMGT Scientific chart based on
      IMGTONTOLOGY. IMGT tools are particularly useful for the analysis of the IG and
      TR repertoires in physiological normal and pathological situations. IMGT has
      important applications in medical research (autoimmune diseases, AIDS,
      leukaemias, lymphomas, myelomas), biotechnology related to antibody engineering
      (phage displays, combinatorial libraries) and therapeutic approaches (graft,
      immunotherapy). IMGT is freely available at http://imgt.cines.fr.

PMID- 14712936
TI  - Generating data for databases--the peptide repertoire of HLA molecules.
AB  - During the past few years, a huge amount of information about HLA-presented
      peptides has been compiled: several thousand naturally processed ligands of such
      cell surface receptors are already known. Nevertheless, our knowledge covers only
      a minute proportion of the total peptide repertoire. The overall amount of
      different peptides presented by one given HLA class I molecule lies between 1000
      and 10000 individual sequences per cell. There is, however, no HLA molecule of
      which more than 100 ligands have been published so far. The situation is further
      complicated by the fact that different cells present different sets of peptides
      by the same HLA molecules, a feature that provides great hope for immunotherapy.
      We have been analysing HLA-presented peptides for many years for three reasons.
      First, the basic rules of peptide presentation (the 'peptide motifs') had to be
      established. Second, the listing of individual peptides presented by HLA
      molecules is steadily continuing, although a comprehensive catalogue of all
      possible HLA-presented peptides is utopical in our days. Third, quantitative
      differences in the presentation of individual HLA ligands provide information
      about the dynamic state of the host cells. Comprehensive information about HLA
      presented peptides enables accurate epitope prediction and provides a basis for
      diagnostic assessment and therapeutic intervention.

PMID- 14712937
TI  - HLA nomenclature and the IMGT/HLA sequence database.
AB  - Early in their study it was recognized that the genes encoding the HLA molecules
      were highly polymorphic and that there was a need for a systematic nomenclature.
      The result was the WHO Nomenclature Committee for Factors of the HLA System,
      which first met in 1968, and laid down the criteria for successive meetings. This
      committee meets regularly to discuss issues of nomenclature and has published 16
      major reports documenting firstly the HLA antigens and more recently the genes
      and alleles. The standardization of HLA antigenic specificities has been
      controlled by the exchange of typing reagents and cells in the International
      Histocompatibility Workshops. Since 1989 when a large number of HLA allele
      sequences were first analysed and named, the job of curating and maintaining a
      database of sequences has been of prime importance. In 1998 the IMGT/HLA database
      became the official repository for HLA sequences. In addition to the nucleotide
      and protein sequences the database contains information of the cell from which
      the sequence was obtained. The database which provides tools for sequence
      analysis and the submission of new data, is updated quarterly and now contains
      over 1500 HLA allele sequences.

PMID- 14712938
TI  - From immunogenetics to immunomics: functional prospecting of genes and
      transcripts.
AB  - Human and mouse genome and transcriptome projects have expanded the field of
      'immunogenetics' beyond the traditional study of the genetics and evolution of
      MHC, TCR and Ig loci into the new interdisciplinary area of 'immunomics'.
      Immunomics is the study of the molecular functions associated with all immune
      related coding and non-coding mRNA transcripts. To unravel the function,
      regulation and diversity of the immunome requires that we identify and correctly
      categorize all immune-related transcripts. The importance of intercalated genes,
      antisense transcripts and non-coding RNAs and their potential role in regulation
      of immune development and function are only just starting to be appreciated. To
      better understand immune function and regulation, transcriptome projects (e.g.
      Functional Annotation of the Mouse, FANTOM), that focus on sequencing full-length
      transcripts from multiple tissue sources, ideally should include specific immune
      cells (e.g. T cell, B cells, macrophages, dendritic cells) at various states of
      development, in activated and unactivated states and in different disease
      contexts. Progress in deciphering immune regulatory networks will require the
      cooperative efforts of immunologists, immunogeneticists, molecular biologists and
      bioinformaticians. Although primary sequence analysis remains useful for
      annotation of new transcripts it is less useful for identifying novel functions
      of known transcripts in a new context (protein interaction network or pathway).
      The most efficient approach to mine useful information from the vast a priori
      knowledge contained in biological databases and the scientific literature, is to
      use a combination of computational and expert-driven knowledge discovery
      strategies. This paper will illustrate the challenges posed in attempts to
      functionally infer transcriptional regulation and interaction of immune-related
      genes from text and sequence-based data sources.

PMID- 14712939
TI  - Mathematical models of HIV and the immune system.
AB  - I describe how mathematical models have been used to elucidate the principles
      which govern HIV and immune system dynamics in relation to antiviral drug
      therapy. The review starts by introducing a basic model of virus infection and
      demonstrates how it was used to study HIV dynamics and to measure crucial
      parameters which lead to a new understanding of the disease process. Since this
      analysis indicates that eradication of the virus is not feasible during the
      lifetime of the patient, I continue to discuss mathematical models with the aim
      to explore how drug therapy can be used to induce long-term immunological control
      of the infection.

PMID- 14712940
TI  - Immunogenomics: towards a digital immune system.
AB  - One of the major differences that set apart vertebrates from non-vertebrates is
      the presence of a complex immune system. Over the past 400-500 million years,
      many novel immune genes and gene families have emerged and their products form
      sophisticated pathways providing protection against most pathogens. The Human
      Genome Project has laid the foundation to study these genes and pathways in
      unprecedented detail. Members of the immunoglobulin (Ig) superfamily alone were
      found to make up over 2% of human genes possibly constituting the largest gene
      family in the human genome. A subgroup of these human immune genes, those (among
      others) involved in antigen processing and presentation, are encoded in a single
      region, the major histocompatibility complex (MHC) on the short arm of chromosome
      6. My laboratory has a long-standing interest in understanding the molecular
      organization and evolution of the MHC. To this end, we have been generating a
      range of MHC genomic resources that we make available in the form of maps and
      databases. Much of the complex data of the immune system can be reduced to binary
      (on/off) information that can easily be made available and analysed by
      bioinformatics approaches, thus contributing to better understand immune function
      via a 'digital immune system'.

PMID- 14712941
TI  - Viral bioinformatics: computational views of host and pathogen.
AB  - Wherever cellular life occurs, viruses are also found. As a result, complex
      organism and cellular antiviral responses co-evolve with virally encoded
      countermeasures. Since viruses co-opt or interfere with specific cellular
      pathways during their replication, knowledge of viral genome sequences has helped
      fundamental understanding of host biology. During viral infection, shifts in the
      balance between host and viral biological processes result in acute or chronic
      viral disease pathology accompanied with either active viral replication, viral
      containment/persistence or viral clearance. Studying host-virus interactions at
      the level of single gene effects, however, fails to produce a global systems
      level understanding. This should now be achievable in the context of complete
      host and pathogen genome sequences. New experimental methods and computational
      approaches are rapidly developing, allowing global views of dynamic viral and
      cellular molecular mechanisms. Systems level virology using DNA microarrays and
      specific viral data resources will reveal the detailed cellular context in which
      viruses replicate, highlighting common and distinct antiviral mechanisms, the
      effect of different host cell gene expression programs, and the response of cells
      to similar or diverse virus types. Ultimately, microbiology and immunology will
      tend towards a systems-level view of how host and pathogen interact.

PMID- 14712942
TI  - Dr Mitchell Henry O'Sullivan's bag.

PMID- 14712943
TI  - Gynaecological malignancies in pregnancy: a review.
AB  - Gynaecological malignancies frequently occur in women of reproductive age and are
      estimated to complicate approximately one in 1000 pregnancies. The incidence of
      gynaecological malignancies during pregnancy is expected to rise as more women
      delay childbearing into their later reproductive years, and maternal age is the
      most powerful predictor of cancer risk. Pregnancy-associated malignancies present
      significant challenges as a result of the conflict between optimal maternal
      therapy and fetal well-being. The lack of prospective randomised treatment
      studies has prevented the development of clinical guidelines for most of the
      issues complicating the management. In the present review, recent diagnostic and
      treatment strategies for cervical, ovarian, vulvar and endometrial carcinomas
      during pregnancy are presented.

PMID- 14712944
TI  - Risk factors for hypertension during pregnancy in South Australia.
AB  - OBJECTIVE: To identify risk factors for hypertension in pregnancy among South
      Australian women. DESIGN: A population-based retrospective analysis using the
      South Australian perinatal data collection for 1998-2001. METHODS: Three groups
      of women with hypertension (pre-existing hypertension, pregnancy hypertension,
      and superimposed pre-eclampsia) were compared with normotensive women using
      unconditional logistic regression analysis on 70,386 singleton births to identify
      sociodemographic and clinical risk factors for hypertension in pregnancy.
      RESULTS: Nulliparity, Aboriginal race and Caucasian race (compared with Asian)
      and pre-existing and gestational diabetes were demonstrated to be risk factors
      for all hypertensive disorders, as was increasing maternal age for pre-existing
      hypertension and superimposed pre-eclampsia. Risk was increased for pregnancy
      hypertension and superimposed pre-eclampsia among women who gave their occupation
      as 'home duties' and also for superimposed pre-eclampsia among unemployed women.
      Women with hypertension were more likely to give birth in teaching hospitals.
      Urinary tract infections were not found to be a risk factor for any type of
      hypertension. Smoking during pregnancy was protective for all types of
      hypertension. CONCLUSIONS: The present study used a statewide population
      perinatal database and has confirmed that Aboriginal race, Caucasians,
      nulliparity, and pre-existing and gestational diabetes are independent risk
      factors for all types of hypertension in pregnancy. Increasing maternal age
      increased the risk for pre-existing hypertension and superimposed pre-eclampsia.
      There appeared to be appropriate referral of women with hypertensive disorders to
      teaching hospitals. A new finding is the increased risk among unemployed women
      and women engaged in home duties.

PMID- 14712945
TI  - Admissions to neonatal intensive care unit following pregnancies complicated by
      gestational or type 2 diabetes.
AB  - BACKGROUND: When gestational diabetes mellitus (GDM) is diagnosed in a population
      with a high prevalence of unrecognised type 2 diabetes mellitus (type 2 DM), the
      rate of neonatal morbidity is not clear. There is also a paucity of data
      reporting neonatal outcome in women with recognised type 2 DM. AIM: To describe,
      in a population with a high background prevalence of type 2 DM, neonatal
      morbidity in infants of women with GDM and type 2 DM admitted to the neonatal
      intensive care unit (NICU). METHODS: A 2-year audit was carried out in a tertiary
      level obstetric hospital with a multi-ethnic delivery population. All infants
      admitted to the NICU whose mothers had GDM or type 2 DM were identified from the
      hospital database. The records of 136 infants were retrospectively reviewed and
      data collected on outcome measures including maternal diagnosis, macrosomia, mode
      of delivery, delivery complications, hypoglycaemia, respiratory distress and
      congenital anomalies. RESULTS: Admission to NICU occurred in 29% of GDM and 40%
      of type 2 DM pregnancies. Median gestation was 37 weeks (range: 25-41), with 46%
      delivered preterm. Forty percent of infants were delivered by emergency Caesarean
      section. Fifty-one percent of admissions had hypoglycaemia and 40% required
      support for respiratory distress. Women with type 2 DM diagnosed either
      prepregnancy or post-partum were the highest risk group for neonatal morbidity,
      including congenital anomalies. CONCLUSIONS: Neonatal morbidity is common in
      infants of women with type 2 DM and GDM in a population with high prevalence of
      type 2 DM.

PMID- 14712946
TI  - Placental biopsy by frozen section: does it have a role in evaluation of fetal
      well-being?
AB  - AIM: To assess the effectiveness of post-partum placental biopsy and frozen
      section evaluation in diagnosing pregnancy disorders. STUDY DESIGN: Between
      January and July 1998, biopsies were carried out on 100 newly delivered
      placentas. Biopsies were carried out using a 14-gauge needle, and frozen section
      evaluations were reviewed. These were compared to the standard evaluation of
      histological evaluation of the whole placenta sections. Specimens were evaluated
      by standard placental pathologic criteria. RESULTS: Villous oedema which is
      associated with antenatal hypoxia was observed with a sensitivity of 78%, and
      specificity of 97%, yielding a positive predictive value of 84% in frozen section
      compared to standard placental evaluation. No statistical difference was observed
      in the evaluation of dysmaturity, intravillous fibrin agglutination and chronic
      villitis between frozen sectioning and whole placenta sections. Increased
      syncytial knots were detected with a sensitivity of 45% and specificity of 98%.
      CONCLUSION: Placental biopsy by frozen sectioning might be a useful and quick
      method of evaluation for placental pathology. Theoretically, fetal status could
      be more precisely evaluated by combining prenatal placental biopsy by permanent
      section with conservative ante-partum well-being tests.

PMID- 14712947
TI  - Association between first trimester maternal serum pregnancy associated plasma
      protein-A and adverse pregnancy outcome.
AB  - AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A)
      levels in the first trimester of pregnancy are associated with subsequent
      intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS:
      A retrospective review of pregnancy outcomes was undertaken in women who had PAPP
      A carried out in the first trimester of pregnancy at the time of nuchal
      translucency scan. Pregnancy outcomes were assessed by the review of medical
      records, and postal questionnaires. Delivery details were collected, including
      livebirth, neonatal birthweight and gestational age at delivery. The chi2 test
      was used to investigate the association between low first trimester serum PAPP-A
      levels and adverse fetal outcomes. Unpaired t-test was used for continuous
      variables. Sensitivities and specificities were then calculated. RESULTS: A total
      of 894 women who had blood collected for PAPP-A were identified, and data was
      obtained for 827 deliveries. Each had a normal karyotype. There were six
      intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies
      weighing below the 10th centile, and 96 women who delivered prematurely. Four of
      six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median),
      with a relative risk of 13.75. Low PAPP-A levels were associated with fetal
      weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no
      statistically significant association between low maternal serum PAPP-A levels
      and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum
      PAPP-A levels are associated with fetal death in utero and birthweight below the
      10th centile. First trimester PAPP-A may be a useful tool for identifying
      pregnancies at risk of adverse fetal outcomes.

PMID- 14712948
TI  - Findings on potential teratogens from a case-control study in Western Australia.
AB  - OBJECTIVES: To examine, in Western Australian women, pregnancy use of drugs that
      have been found to be associated with birth defect risks in other studies.
      DESIGN: Data were used from a retrospective study of birth defects in which
      mothers were sent questionnaires asking about a variety of pregnancy events and
      exposures, including specific questions on medication use. POPULATION: Case
      subjects were fetuses or infants with structural birth defects born in Western
      Australia from 1997 to 2000, identified from the Western Australian Birth Defects
      Registry. Control subjects were infants without birth defects, randomly selected
      from the Western Australian Midwives' Notification System. MEASURES: First
      trimester uses of corticosteroids, medications that antagonise folic acid
      metabolism, and vasoactive drugs were compared between case and control mothers.
      RESULTS: The mothers of 2.5, 2.4, and 1.9% of controls, cases, and oral cleft
      cases, respectively, reported corticosteroid use. The mothers of 0.6% of controls
      and 1.4% of cases used a folic acid antagonising medication, yielding an odds
      ratio of 2.3 (95% confidence interval, 0.58-9.4). The mothers of 4.5% of controls
      and 7.1% of cases used a vasoactive drug (pseudoephedrine, aspirin, ibuprofen,
      amphetamine, cocaine, or ecstasy). Cigarette smoking is also vasoactive. For
      exposure to both a vasoactive drug and cigarette smoking, the birth defect risk
      was 3.0 (0.92-9.6). CONCLUSIONS: There was no difference in corticosteroid use
      between case and control mothers, although the number of exposed subjects was
      small. Odds ratio estimates for folic acid antagonists and vasoactive agents
      support previously reported associations, but they were not statistically
      significant.

PMID- 14712949
TI  - Diagnostic value of sonohysterography in the evaluation of submucosal fibroids
      and endometrial polyps.
AB  - AIMS: To evaluate the diagnostic value of sonohysterography in the evaluation of
      submucosal fibroids and endometrial polyps. METHODS: Thirty-two women whose
      preliminary transvaginal ultrasound suggested endometrial abnormality underwent
      sonohysterography. The findings were then compared with histopathological
      results. RESULTS: The sonohysterographic diagnosis was fibroid in seven patients,
      endometrial polyp in 23 patients and simple hyperplasia in two patients.
      Histopathological findings confirmed our diagnosis in all except three patients
      with endometrial polyps, who had normal secretory endometrium. Sonohysterography
      was found to have a sensitivity of 100%, a positive predictive value of 90% and
      diagnostic accuracy of 90.6%. CONCLUSION: Sonohysterography is a useful,
      minimally invasive and accurate technique to evaluate the pathologies involving
      endometrium and uterine cavity.

PMID- 14712950
TI  - Ultrasound assessment of bladder volume: is it valid after delivery?
AB  - AIM: To assess the validity of a commercially available bladder volume scanner in
      the puerperium. METHODS: A prospective blinded comparison of bladder volume
      measurement after vaginal delivery using the BladderScan bladder volume
      instrument (BVI) 3000 and Foley catheter; comparison using the intraclass
      correlation coefficient. RESULTS: The mean difference between the two
      measurements was a 130-mL over-measurement by the bladder scanner (range: -156 mL
      to +422 mL). The intraclass correlation coefficient was 0.23 (95% confidence
      interval 0.00, 0.59). CONCLUSIONS: The BladderScan BVI 3000 is not an accurate
      instrument to assess bladder volume the day after vaginal delivery. Some of the
      discrepancy might relate to use of the Foley catheter as the reference standard.
      Further comparison between the BladderScan and a short female catheter or real
      time ultrasound is indicated.

PMID- 14712951
TI  - Antenatal screening for sexually transmitted infections in remote Australia.
AB  - BACKGROUND: Antenatal screening for, and prompt management of, sexually
      transmitted infections (STI) can prevent adverse maternal, fetal and perinatal
      outcomes. This is particularly important in areas of high STI endemicity. AIMS:
      To assess adherence with antenatal STI screening guidelines in a large remote
      region, and whether completeness of antenatal syphilis screening improved after
      the onset of a regional syphilis outbreak in April 2001. METHODS: Data from the
      regional antenatal syphilis screening database from 1997 to 2002 were analysed to
      identify time trends in the completeness of antenatal syphilis screening.
      Adherence to antenatal screening guidelines was assessed by examining pathology
      request forms of women undergoing antenatal syphilis screening to determine
      whether screening for gonorrhoea, chlamydia, hepatitis B and HIV had also been
      carried out. Logistic regression was used to analyse associations between
      adherence to the guidelines and patient's age and race, and health service
      characteristics. RESULTS: Adherence to syphilis screening guidelines improved
      from 44.6% in 1997 to 68.9% in 2001 and 81.4% in 2002. After controlling for the
      time interval between the first antenatal syphilis test and date of delivery,
      being younger and Aboriginal, and delivering after the syphilis outbreak had been
      identified were positively associated with adherence to syphilis screening
      guidelines. Proportions of antenates screened for gonorrhoea/chlamydia, hepatitis
      B and HIV at booking and for gonorrhoea/chlamydia in the third trimester were
      69%, 91%, 68% and 77%, respectively. Aboriginal women were more likely to have
      been screened for gonorrhoea and chlamydia. Women seen by a doctor were more
      likely to have undergone HIV screening than those who saw a nurse. CONCLUSIONS:
      Significant improvement in adherence to antenatal syphilis screening guidelines
      occurred after identification of a syphilis outbreak. This achievement is reason
      for optimism regarding the potential to achieve more complete antenatal screening
      of other STI.

PMID- 14712952
TI  - Maternal satisfaction with childbirth and intrapartum analgesia in nulliparous
      labour.
AB  - OBJECTIVE: To assess maternal satisfaction with childbirth and intrapartum pain
      relief in nulliparous women labouring at term. METHODS: Prospective randomised
      clinical trial comparing epidural and non-epidural analgesic techniques on term
      labour outcomes in nulliparous women. Within 24 h of delivery the women were
      surveyed regarding their opinions about the birthing experience and the allocated
      analgesic regimen. A postal survey was conducted 6 months postpartum to assess
      opinions about intrapartum analgesia in a subsequent pregnancy. RESULTS: A total
      of 992 women were randomised to receive continuous midwifery support (CMS) or
      epidural (EPI) analgesia on presentation for delivery. There was a high crossover
      rate from CMS to EPI (61.2%) and a lesser non-compliance rate in the EPI group
      (27.8%). The early post-partum recollections revealed a high satisfaction with
      epidural analgesia and lower satisfaction with alternative pain relief measures.
      Ten percent of women in the CMS group reported negative feelings about their
      allocated pain relief compared with 1% in the EPI group (P < 0.001), and 10% of
      all women reported negative feelings about their overall childbirth experience.
      At the 6-month postpartum survey factors associated with the planned use of
      epidural analgesia in a subsequent pregnancy were induction of labour (odds ratio
      (OR) 2.4, 95% confidence interval (CI) 1.2, 4.7) and prior utilisation of
      epidural analgesia (OR 28.1, 95% CI 14.5, 54.7). CONCLUSIONS: Maternal
      satisfaction with intrapartum analgesia was significantly higher with epidural
      analgesia than non-epidural analgesic techniques. Overall satisfaction scores for
      labour and delivery were high regardless of analgesic approach, reflecting the
      multiple issues other than pain relief that are involved in the childbirth
      experience.

PMID- 14712953
TI  - Gestational diabetes mellitus: compliance with testing.
AB  - An audit of birth records of two public and one private hospital was undertaken,
      over a 6-month period, to determine compliance with the local policy that all
      women are tested for gestational diabetes mellitus (GDM). Overall 92.1% of women
      were tested for GDM. When those women who delivered their babies early or who had
      no prenatal care were excluded, then there was 95.3% compliance with the advice
      for universal testing.

PMID- 14712954
TI  - Successful vaginal birth after three previous Caesarean sections with no prior
      labour.

PMID- 14712955
TI  - Cervical hydatidiform molar pregnancy.

PMID- 14712956
TI  - Placental mesenchymal dysplasia: a report of four cases with differentiation from
      partial hydatidiform mole.

PMID- 14712957
TI  - Re: Oestrogens, triglycerides and pancreatitis.

PMID- 14712958
TI  - Delivery-related perinatal death and vaginal birth after Caesarean section.

PMID- 14712959
TI  - Early obstetric atlas.

PMID- 14712960
TI  - Quest for patient safety in a challenging environment.
AB  - We are unable to guarantee our patients that the care we provide will do no harm.
      Up to 16% of hospital admissions will be associated with an adverse event,
      approximately half of which are preventable. It is a clinical imperative that we
      must strive to improve patient safety by improving the systems in which we work,
      such that they support us in providing better and safer care. For this to occur,
      an environment must develop where clinicians feel safe to report and allow
      analysis of adverse events and near misses. The greatest inhibitor of a reporting
      culture is the prevailing legal climate with its associated blame culture. A new
      social contract is required whereby systems analysis will predominate over the
      previous presumption that individual clinicians must be held responsible for each
      and every adverse outcome. Individual responsibility should be reserved for
      events where it becomes evident during the course of systems analysis that an
      individual's behaviour is truly blameworthy.

PMID- 14712961
TI  - Effects of a single course of corticosteroids given more than 7 days before
      birth: a systematic review.
AB  - OBJECTIVES: To determine the risk of fetal, neonatal and maternal mortality and
      morbidity for women and their infants who remained undelivered more than 7 days
      following a course of prenatal corticosteroids. DESIGN: Systematic review.
      POPULATION: Women who gave birth more than 7 days after a course of prenatal
      corticosteroids compared with women not administered corticosteroids. METHODS:
      Seven randomised controlled trials were identified which reported outcomes for
      women and their babies who remained undelivered more than 7 days after exposure
      to a single course of corticosteroids compared with a placebo/no treatment group.
      MAIN OUTCOME MEASURES: Fetal, neonatal and maternal mortality and morbidity.
      RESULTS: Seven trials involving 862 infants, 434 born to corticosteroid treated
      women and 428 to control women were included in this review. For corticosteroid
      treated infants there was no reduction in the risk of respiratory distress
      syndrome (relative risk (RR), 0.72; 95% confidence interval (CI), 0.49-1.07), or
      stillbirth (RR, 1.67; 95% CI, 0.86-3.25). However, there was a tripling in risk
      of death for liveborn corticosteroid treated infants (RR, 3.24; 95% CI, 1.32
      7.96; P = 0.01), and a doubling in risk of perinatal mortality (RR, 2.13; 95% CI,
      1.27-3.57; P < 0.01). Corticosteroid treated infants were born on average 5 days
      earlier than controls (95% CI, -9.15 to -0.85 days, P = 0.02). Their mothers were
      more likely to have chorioamnionitis (RR, 2.91; 95% CI, 1.25-6.74; P = 0.01).
      CONCLUSIONS: Infants exposed to corticosteroids more than 7 days before birth had
      no reduction in risk of respiratory distress syndrome but increased perinatal
      mortality.

PMID- 14712962
TI  - Consensus statement: The management of congenital genital tract anomalies in
      women.

PMID- 14712963
TI  - Consensus statement: Menstrual and contraceptive management in women with an
      intellectual disability.

PMID- 14712964
TI  - Anatomy of Complications workshop: an educational strategy to improve performance
      in obstetricians and gynaecologists.
AB  - Many specialist obstetricians and gynaecologists feel inadequately trained to
      deal with certain situations such as injury to bowel, bladder, ureter and major
      vessels, and value further training to prevent and manage these problems. We
      present the structure, objectives and rationale for a surgical skills workshop,
      which is an intensive practical learning experience aimed to improve the
      performance of obstetricians and gynaecologists. The overall objective of the
      workshop is improvement in the prevention and management of complications in
      obstetric and gynaecological surgery. Over 100 participants have completed the
      workshop so far. Pre-workshop preparation includes anatomical illustrations to
      guide reading and a training video describing surgical skills, ewe anatomy and
      hysterectomy in the ewe. There are four modules: anatomy includes an interactive
      lecture, cadaveric dissection and examination of prosections with specific
      learning tasks. Surgical skills involves the demonstration, practice and learning
      of techniques needed to deal with unexpected operative injury to bowel, bladder,
      ureter and major blood vessels. Live animal surgery on a ewe allows further
      supervised practice of the previously learned skills plus the repair of serious
      vascular injury. Case presentations allow each participant to present a
      complicated case in a facilitated group session with discussion and feedback from
      their peers. This session is controlled, non-threatening and a valuable
      interactive learning experience. Participant feedback suggests that this workshop
      format is useful and appears to improve the confidence, competence and
      performance of the participants. This workshop is presented as a template on
      which other educational activities can be developed.

PMID- 14712965
TI  - Value of a structured participant evaluation questionnaire in the development of
      a surgical education program.
AB  - OBJECTIVE: To describe how the summative evaluation of attitudes and perceptions
      of participants at a surgical skills workshop influences and contributes to the
      development of the workshop. MATERIALS AND METHODS: One hundred participants from
      11 workshops were invited to complete a structured scored anonymous questionnaire
      with 18 statements, at the end of each workshop. Space was provided for free
      comment next to each statement. The questionnaire covered all aspects of the
      workshop including the practical modules, learning materials, organisation,
      facilitators and the relevance of the workshop to their needs. Ninety-eight of
      the 100 participants returned the questionnaire and this analysis is based on
      their responses. RESULTS: All respondents considered the workshop content,
      structure and facilities enabled the educational objectives to be achieved. The
      scored responses to the structured statements helped to determine the degree of
      satisfaction with the workshop domains, but did not give direction for change.
      The informal 'free' comments gave insight as to how improvements could be
      achieved in specific domains. Numerous changes suggested by participants have
      been included in subsequent workshops. CONCLUSION: Summative evaluation of an
      educational program is important to determine participant satisfaction and to
      determine areas needing improvement. Structured scored questionnaires are helpful
      in determining levels of satisfaction with the various domains of the program.
      Informal written comments allow insight into specific areas requiring improvement
      and may provide guidance as to how improvement can be achieved. Space for such
      comment should be encouraged in any program evaluation questionnaire.

PMID- 14712966
TI  - Hepatitis B surface antigen carrier status and its correlation to gestational
      hypertension.
AB  - OBJECTIVE: To determine whether chronic hepatitis B surface antigen (HBsAg)
      carrier status is associated with an increased incidence of gestational
      hypertension. METHODS: A retrospective analysis of all deliveries in a regional
      obstetric unit over a 4-year period using a comprehensive obstetric database.
      RESULTS: The data of 13,792 patients were analysed, of which 1340 (9.71%) were
      chronic HBsAg carriers. Contrary to our hypothesis, the overall incidence of
      gestational hypertension was significantly lower in the HBsAg positive group
      (2.01%) as compared to the negative group (3.58%) (P < 0.01, odds ratio (OR)
      0.55, 95% confidence interval (CI) 0.37-0.81). When comparing the incidence of
      severe preeclampsia, the difference remained significant (0.22 and 0.79%,
      respectively, P < 0.05, OR 0.28, 95% CI 0.08-0.88). There was otherwise no
      difference in the incidence of other major obstetric complications between the
      HBsAg positive and negative groups. CONCLUSION: The findings presented did not
      support a positive association between HbsAg carrier status and gestational
      hypertension. The data from the present study, and re-evaluation of similar
      published data, in fact suggest the contrary observation of a lower than normal
      incidence of gestational hypertension in HbsAg positive mothers.

PMID- 14712967
TI  - Prophylactic and therapeutic enoxaparin during pregnancy: indications, outcomes
      and monitoring.
AB  - OBJECTIVES: To evaluate the efficacy and safety of prophylactic and therapeutic
      enoxaparin in pregnancy. STUDY DESIGN: Three-year prospective audit. SETTING:
      Tertiary level obstetric hospital. POPULATION: Fifty-two women who received
      subcutaneous enoxaparin, either a prophylactic dose (40 mg daily) in 26
      pregnancies or therapeutic dose (1 mg/kg twice daily) in 32 pregnancies.
      MATERIALS AND METHODS: Pregnant women treated with enoxaparin were prospectively
      entered into a register. Data were retrieved by case note review. MAIN OUTCOME
      MEASURES: Pregnancy outcomes, treatment complications and anti-Xa levels.
      RESULTS: In the prophylactic group there were no fetal losses, thromboembolic
      events or complications related to enoxaparin. In the therapeutic group there
      were four first trimester miscarriages, a termination and 27 live births.
      Therapeutic enoxaparin prevented further thromboembolism without complications.
      One woman was treated with intermediate dose enoxaparin when she presented at 5
      weeks' gestation on warfarin and 7 weeks after a venous thromboembolism. She
      developed a recurrent pulmonary embolus 3 weeks later and was subsequently
      treated with therapeutic enoxaparin. In the therapeutic group the enoxaparin
      dose/kg correlated poorly with anti-Xa levels, and dose adjustments were made.
      Therapeutic mean (SD) trough and peak anti-Xa levels were 0.33 U/mL (0.14) and
      0.86 U/mL (0.24) in the first trimester and 0.48 U/mL (0.19) and 0.84 U/mL (0.23)
      in the third trimester. CONCLUSIONS: In the present series, prophylactic and
      therapeutic enoxaparin treatment during pregnancy was effective and safe. Studies
      are required to determine the optimal duration of treatment with therapeutic
      enoxaparin following venous thromboembolism in pregnancy and the clinical
      relevance of anti-Xa monitoring.

PMID- 14712968
TI  - Is amniotic fluid volume status predictive of fetal acidosis at delivery?
AB  - OBJECTIVE: To ascertain if dye-determined amniotic fluid volume just prior to
      delivery correlates with fetal acidosis at delivery. DESIGN: The present was a
      prospective observational study. SETTING: The study took place at the University
      of Mississippi Medical Center, Jackson MS, USA. POPULATION: The population
      included 100 unlaboured women undergoing an amniocentesis for the assessment of
      fetal lung maturity before an elective Caesarean delivery between January 1997
      and December 2000. MAIN OUTCOMES MEASURED: The amniotic fluid volume was
      estimated by ultrasound measurement and quantified by dye-determined methodology
      immediately prior to Caesarean delivery. Umbilical cord artery pH was collected
      at the time of Caesarean delivery. RESULTS: The predictive accuracy of an
      amniotic fluid index < or = versus > 5 to identify an umbilical artery pH of <
      7.20 had a sensitivity of 0%, a specificity of 84%, and a likelihood ratio of
      zero. None of the dye-determined low amniotic fluid volumes were identified using
      the single deepest pocket technique. Dye-determined low, normal, and high
      amniotic fluid volume groups contained a similar number of fetuses with umbilical
      cord arterial pH < 7.20 (P = 0.371), < 7.10 (P = 0.460), and < 7.00 (P = 0.614).
      Receiver-operating characteristic curves could not identify any amniotic fluid
      index from 0 to 18, single deepest pocket from 0 to 12, or dye-determined
      amniotic fluid volume 100-1900 mL to differentiate between the two newborns with
      an umbilical cord artery pH < 7 from 98 babies with cord pH > or = 7.0.
      CONCLUSIONS: Neither ultrasound estimates nor dye-determined amniotic fluid
      volumes are predictive of a low umbilical artery pH at delivery.

PMID- 14712969
TI  - Survey of the knowledge, attitudes and experiences of Western Australian women in
      relation to prenatal screening and diagnostic procedures.
AB  - OBJECTIVE: To determine the knowledge, attitudes and experiences of women in
      Western Australia (WA) regarding prenatal procedures. DESIGN: A self-administered
      mail survey. SAMPLE: The survey was sent to all women who gave birth during July
      2001 (n = 1801). The participants were 633 women aged 15-45. RESULTS: The mean
      total knowledge score was 16 out of a possible 26 (62%). The average score for
      all three attitude factors was four, 'agree', on a Likert scale of five. Women
      who reported they had private health insurance and women in the metropolitan area
      had significantly higher knowledge levels and had significantly more positive
      attitudes towards the adequacy of information. Those who did not have a screening
      test had less positive attitudes towards the value of the tests and had less
      confidence in results. Those with higher educational attainments had higher
      knowledge and less positive attitudes towards the value of the tests.
      CONCLUSIONS: Women felt positive towards the value of the tests, were confident
      in their results and felt positive towards the adequacy of information; however,
      their understanding of this information seems to be poor. It seems that the
      choice to undergo testing is not well informed. It was clear women need more
      support, information, explanations, and more time to absorb the information.

PMID- 14712970
TI  - Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled
      trial.
AB  - OBJECTIVE: To investigate the effect of a ginger extract (EV.EXT35) on the
      symptoms of morning sickness. DESIGN: Double-blind randomised placebo-controlled
      trial. SETTING: A tertiary metropolitan teaching hospital, March 1999-November
      1999. PARTICIPANTS: The participants included 120 women less than 20 weeks
      pregnant, who had experienced morning sickness daily for at least a week and had
      had no relief of symptoms through dietary changes. INTERVENTION: Random
      allocation of 125 mg ginger extract (EV.EXT35; equivalent to 1.5 g of dried
      ginger) or placebo given four times per day for 4 days. MAIN OUTCOME MEASURES:
      Nausea, vomiting and retching as measured by the Rhodes Index of Nausea, Vomiting
      and Retching. RESULTS: The nausea experience score was significantly less for the
      ginger extract group relative to the placebo group after the first day of
      treatment and this difference was present for each treatment day. Retching was
      also reduced by the ginger extract although to a lesser extent. No significant
      effect was observed on vomiting. Follow-up of the pregnancies revealed normal
      ranges of birthweight, gestational age, Apgar scores and frequencies of
      congenital abnormalities when the study group infants were compared to the
      general population of infants born at the Royal Hospital for Women for the year
      1999-2000. CONCLUSION: Ginger can be considered as a useful treatment option for
      women suffering from morning sickness.

PMID- 14712971
TI  - Serum lipid and lipoprotein changes induced by preparations containing low-dose
      ethinylestradiol plus levonorgestrel.
AB  - The purpose of the present study was to evaluate the effects on lipid metabolism
      of a new low-dose monophasic combination oral contraceptive with 100 microg
      levonorgestrel and 20 microg ethinylestradiol. Sixty healthy women aged 18-45
      years were administered the medication during three cycles. The study
      participants were screened for lipid changes. The differences in cholesterol and
      triglyceride levels were not statistically significant, but high-density
      lipoprotein levels were significantly lower and low-density lipoprotein levels
      were significantly higher than the baseline. Women at risk of cardiovascular
      disease should be carefully monitored even when using low-dose preparations.

PMID- 14712972
TI  - Aetiology and prevalence of lower limb lymphoedema following treatment for
      gynaecological cancer.
AB  - OBJECTIVE: To determine the prevalence and incidence of lower limb lymphoedema
      (LLL) in a cohort of women who had treatment for gynaecological cancer between
      May 1995 and April 2000. DESIGN: A retrospective survey. SETTING: The study took
      place at an urban referral centre in an Australian tertiary referral women's
      hospital. SAMPLE: The data collection was based on 66% of 743 women on the
      database of the Gynaecological Cancer Centre. METHODS: Interviews and assessments
      were conducted to determine the status of lower limbs; medical records were
      reviewed for age, weight, site and type of cancer and treatment. MAIN OUTCOME
      MEASURES: Leg swelling, diagnosed lower limb lymphoedema, no swelling of the legs
      and type of surgery were determined as the main outcome measures. RESULTS AND
      CONCLUSIONS: The diagnosis of lower limb lymphoedema was made in 18% of the total
      sample: 53% of these were diagnosed within 3 months of treatment, a further 18%
      within 6 months, 13% within 12 months and the remaining 16% up to 5 years
      following treatment. Women most at risk for developing LLL were those who had
      treatment for vulvar cancer with removal of lymph nodes and follow up
      radiotherapy. For this subsample, the prevalence was 47%. The finding that LLL
      occurs within the first year is earlier than hitherto generally believed. It is
      therefore imperative for all health professionals to include care and assessment
      of the legs particularly during the immediate pre- and postoperative period.

PMID- 14712973
TI  - National audit of women with abnormal cervical smears in New Zealand.
AB  - OBJECTIVE: To evaluate the follow-up of women with abnormal cervical smears
      identified by the National Cervical Screening Programme (NCSP) in New Zealand.
      DESIGN: Survey and clinical audit. SETTING: The study took place in New Zealand.
      POPULATION: The population included women aged 20-69 years enrolled on the NCSP
      with first abnormal smear recorded in 1999. METHODS: Participants were
      interviewed, and clinical data collected from the NCSP-register, and from
      clinicians. MAIN OUTCOME MEASURES AND RESULTS: The overall response rate was 57%.
      The proportions of women whose initial assessment, treatment or follow-up fell
      outside recommended times were between 17 and 35%. Of women with high-grade
      smears, 72% underwent a treatment procedure. Of these, 91% were excision
      biopsies, 6% hysterectomies and 4% ablation procedures. Approximately 10% of
      women had persistent or recurrent abnormalities at 6 and 12 months after
      treatment. CONCLUSIONS: Overall, results were largely reassuring, but limited by
      the low response rate. Most women were managed within current clinical
      guidelines. Areas requiring improvement were identified, in particular in
      relation to longer than recommended waiting times for assessment and treatment.

PMID- 14712974
TI  - Twenty-three years of labour floor records, Vila Central Hospital, Vanuatu.
AB  - Vanuatu is an island nation in the south-west Pacific. Vila Central Hospital
      (VCH) is the country's major referral hospital. The handwritten labour floor
      records from VCH between 1979 and 2001 were examined and collated. During this
      period 28,638 women received care. The mean Caesarean section and instrumental
      delivery rate were 5.2% (2.1-8.2% per annum) and 1.8% (0.9-3.2% per annum),
      respectively. The post-partum haemorrhage rate fell from >5% in 1979 to <1% in
      2001. The overall hospital maternal mortality rate was 7/10,000. These records
      represent the largest published series of labour floor data collected from any
      Pacific island nation.

PMID- 14712975
TI  - Maternal complications after Caesarean section in HIV-infected pregnant women.
AB  - A study of maternal complications after elective Caesarean section in HIV
      infected women was carried out from January 1999 to April 2001. The control group
      consisted of all the seronegative pregnant women who underwent the elective
      Caesarean section during the study period. The study group was divided into two
      subgroups. Subgroup 1 patients were given 600 mg zidovudine (ZDV) orally and 300
      mg lamivudine (3TC) daily from 34 to 38 weeks' gestation. Subgroup 2 patients
      were given 600 mg ZDV orally daily from 34 to 38 weeks' gestation and 150 mg
      nevirapine orally on the morning of the Caesarean section day. In both groups,
      the elective Caesarean section was carried out at 38 weeks' gestation and ZDV
      syrup (2 mg/kg) was given orally to the newborn immediately in the operating
      theatre and then every 6 h for 4 weeks. No statistically significant differences
      in maternal complications were found between the HIV-infected and non HIV
      infected women.

PMID- 14712976
TI  - Scar endometriosis presenting as an acute abdomen: a case report.

PMID- 14712977
TI  - Subcutaneous panniculitic T-cell lymphoma presenting as pyrexia of unknown origin
      in pregnancy: a case report and literature review.

PMID- 14712978
TI  - Intussusception of a fallopian tube after dilatation and curettage.

PMID- 14712979
TI  - Management of platelet storage pool deficiency during pregnancy.

PMID- 14712980
TI  - Update on the management of term breech deliveries in New South Wales, Australia.

PMID- 14712981
TI  - 'Sydney summer sign'.

PMID- 14712982
TI  - Victor Bonney's portable operating table.

PMID- 14712983
TI  - Calcium channel blockers for inhibiting preterm labour; a systematic review of
      the evidence and a protocol for administration of nifedipine.
AB  - OBJECTIVE: To assess the effects on maternal, fetal and neonatal outcomes of
      nifedipine (and other calcium channel blockers) administered as a tocolytic agent
      to women in preterm labour. METHODS: Standard methods of the Cochrane
      Collaboration and its Pregnancy and Childbirth Review Group were used. All
      published and unpublished randomised trials in which calcium channel blockers
      were used for tocolysis for women in preterm labour between 20 and 36 weeks'
      gestation, were considered. MAIN RESULTS: The systematic review includes 12
      randomised controlled trials with a total of 1029 participating women. No trials
      were identified in which calcium channel blockers were compared with a placebo or
      no alternative tocolytic treatment. Calcium channel blockers appear to be more
      effective than betamimetic agents in prolonging pregnancy for 7 days or longer,
      are much less likely to cause maternal side-effects and are associated with
      reduced neonatal morbidity. CONCLUSION: Calcium channel blockers (especially
      nifedipine) can be considered safer and more effective tocolytic agents than
      betamimetics.

PMID- 14712984
TI  - Repeat prenatal corticosteroids: who still recommends their use and why?
AB  - BACKGROUND: Repeat prenatal corticosteroids have been in common use worldwide,
      even though the National Institutes of Health recommends that 'Until data
      establish a favourable benefit-to-risk ratio, repeat courses of antenatal
      corticosteroids, including rescue therapy, should be reserved for patients
      enrolled in clinical trials.' OBJECTIVES: To describe the current
      use/recommendations for the use of repeat prenatal corticosteroids by
      obstetricians and neonatologists and to examine the sources of evidence on which
      their practice is based. DESIGN: Postal questionnaire. POPULATION: All Trainees,
      Members and Fellows of the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists and neonatologists in Australia and New Zealand.
      METHODS: The questionnaire was mailed to obstetricians and neonatologists in
      August-September 2001. MAIN OUTCOME MEASURES: Practitioner use/recommendations
      for the use of repeat prenatal corticosteroids and the sources of evidence on
      which their practice was based. RESULTS: Use of repeat prenatal corticosteroids
      was recommended by 332 (44%) obstetricians and 19 (21%) neonatologists.
      Obstetricians were twice as likely to recommend their use compared with
      neonatologists (relative risk, 2.04; 95% confidence intervals, 1.36-3.06; P <
      0.001). Over half of the respondents (483, 57%) reported they had changed their
      use/recommendations in the previous 3 years. The sources of evidence behind these
      practices differed between obstetricians and neonatologists and between those
      practitioners who recommended the use of repeat prenatal corticosteroids and
      those who did not. CONCLUSIONS: Fewer practitioners recommend repeat prenatal
      corticosteroids compared with previous surveys. Sources of evidence behind the
      practice of groups of obstetricians and neonatologists differ.

PMID- 14712985
TI  - Effect of inter-twin delivery time on Apgar scores of the second twin.
AB  - OBJECTIVE: The aim of the present study was to analyse the effect of inter-twin
      delivery time on the Apgar scores of the second twin. MATERIAL: Women attempting
      vaginal delivery of second twins were studied in 2000. Deliveries before 25
      weeks' gestation, complicated pregnancies, operative deliveries, and deliveries
      by regional or general anaesthesia were all excluded. RESULTS: A total of 37 out
      of 126 twin pregnancies had the criteria to be included in the present study. The
      major factor identified to influence Apgar scores was gestational age (P < 0.01).
      There was a linear relationship between delivery interval and the Apgar scores of
      the second twin, and the addition of delivery interval significantly improved the
      predictivity of gestational age. There was no influence of presentation and
      delivery mode of the second twin. Interval was found to be the only significant
      predictive factor of the Apgar scores in second twins of >1900 g and where the
      second twin is in a breech presentation. Caesarean section did not improve the
      outcome of the second twins. CONCLUSION: Gestational age is the most important
      factor influencing the Apgar scores of second twins. The addition of delivery
      interval improves the predictivity of second twin Apgar score by gestational age.
      Inter-twin delivery time of >15 min is particularly important in the second twin
      which presents by the breech method and in the second twin of more than 1900 g.

PMID- 14712986
TI  - Cost-effectiveness and patient satisfaction with pregnancy day care for
      hypertensive disorders of pregnancy.
AB  - OBJECTIVE: To quantify the cost-effectiveness of, and evaluate patient
      satisfaction with, day care for management of hypertensive disorders of
      pregnancy. DESIGN: Retrospective descriptive study. SETTING: Pregnancy Day Care
      Centre, Royal Women's Hospital, Melbourne. SAMPLE: A total of 1200 consecutive
      women attending with a hypertensive disorder of pregnancy. METHODS:
      Sociodemographic details and perinatal outcome were entered in a purpose designed
      computer program. A satisfaction questionnaire was administered to 130 women.
      Clinical costing data were calculated by casemix analysts to compare traditional
      inpatient and day care models of care. RESULTS: An admission to the Pregnancy Day
      Care Centre cost an average of 684.85 dollars less than a traditional inpatient
      admission. Women had an overwhelming preference for day care. CONCLUSION:
      Pregnancy day care is a cost-effective method of providing care for women with
      hypertensive disorders of pregnancy. Women prefer day care to inpatient care.

PMID- 14712987
TI  - Effect of oestrogen replacement therapy on serum lipid profile.
AB  - BACKGROUND: Oestrogen deficiency in postmenopausal women alters the lipid
      metabolism unfavourably. AIM: To evaluate the effects of oral and transdermal
      oestrogen replacement therapy (ORT) on serum lipid profile. METHODS: Ninety
      hysterectomised and oophorectomised women were randomised into three equal groups
      (no hormones; oral conjugated equine oestrogen, 0.625 mg/day; transdermal
      oestradiol patches, 50 microg/day). Serum concentrations of total cholesterol,
      high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL)
      cholesterol and triglycerides were determined at the baseline and after 3 and 6
      months of therapy. Student's t-test was used for statistical evaluation. RESULTS:
      Most of the hysterectomised women had abnormal serum lipid profile, especially
      HDL cholesterol levels (less than 40 mg/dL in 87%). A significant decline in the
      levels of serum cholesterol (total) as well as LDL and a significant increase in
      HDL cholesterol levels were observed following ORT by both modes, the response
      being comparatively rapid with oral route. After 3 and 6 months, the number of
      cases with HDL cholesterol levels above 40 mg/dL increased from initial 13 to 63%
      and 87% (oral) and 30 and 60% (transdermal), respectively. Serum triglyceride
      levels declined significantly with transdermal therapy but increased with oral
      ORT. CONCLUSIONS: Oestrogen replacement therapy either via oral or transdermal
      route has a beneficial effect on serum lipid profile of menopausal women. Whereas
      the oral route is more effective in increasing HDL cholesterol levels, the
      transdermal route is better for reducing the serum triglyceride level; hence, the
      latter should be the route of choice in women with high serum triglyceride
      levels.

PMID- 14712988
TI  - Down syndrome screening: what do health professionals know?
AB  - OBJECTIVE: To assess the level of knowledge about Down syndrome screening among a
      sample of health professionals providing antenatal care. DESIGN: A structured
      questionnaire-based survey. SETTING: Health professionals allied to a tertiary
      level maternity hospital in metropolitan Melbourne. METHODS: A self-administered
      questionnaire was given or posted to 166 health care providers to assess their
      knowledge of prenatal Down syndrome screening. RESULTS: A total of 140 completed
      surveys were returned (83% response rate), including 70 from general
      practitioners, 34 from midwives, 33 from obstetricians and three from
      geneticists. Of these, 130 confirmed that they regularly counsel women about
      prenatal screening for Down syndrome. Sixteen per cent of those indicated that
      they only offered testing to selected 'high risk' women rather than all women.
      Overall, there was a high level of awareness regarding the gestations at which
      the commonly used screening tests are offered but a poor appreciation of the
      relative performances of those tests. Seventy-eight (60%) of those counselling
      indicated that they discussed detection and screen positive rates specific for
      the age of the woman. However, less than 10% were able to provide those rates.
      CONCLUSION: Knowledge of Down syndrome screening was variable among those who
      regularly counsel women about these tests. The results of the present survey
      highlight the need for professional education about prenatal screening.

PMID- 14712989
TI  - Survey of current prenatal screening for Down syndrome in Australian hospitals
      providing maternity care.
AB  - BACKGROUND: The present study assessed the screening tests for Down syndrome
      available to women within Australian hospitals. METHODS: Postal questionnaires.
      RESULTS: A total of 282 (57%) hospitals responded with over two-thirds offering
      some form of screening test which varied by geographical region and level of
      institution. First trimester maternal serum screening was offered by 11% of
      hospitals. Nuchal translucency screening was offered by 52% of hospitals with
      higher use in Australian Capital Territory and New South Wales than in the other
      regions. Second trimester maternal serum screening was offered by 75% of
      hospitals with higher rates in Australian Capital Territory, South Australia and
      the lowest rate in Queensland. CONCLUSIONS: A high proportion of women are
      offered screening but with wide variation in the tests used.

PMID- 14712990
TI  - Vaginal birth after Caesarean section: a survey of practice in Australia and New
      Zealand.
AB  - AIMS: Women with a single prior Caesarean section (CS) in a subsequent pregnancy
      will be offered either a planned elective repeat CS or vaginal birth after
      Caesarean (VBAC). Recent reports of VBAC have highlighted risks of increased
      morbidity, including uterine rupture, and adverse infant outcome. A survey of
      practice was sent to fellows and members of the Royal Australian and New Zealand
      College of Obstetricians and Gynaecologists to determine current care for women
      in a subsequent pregnancy with a single prior CS, and to assess variations by
      length and type of obstetric practice. METHODS: Questions asked about the safety
      of VBAC, induction of labour with a uterine scar, and requirements to conduct
      VBAC and elective repeat CS. RESULTS: A total of 1641 surveys were distributed,
      with 1091 (67%) returned, 844 from practicing obstetricians (51% of college
      membership). Almost all respondents (96%) agreed or strongly agreed that VBAC
      should be presented as an option to the woman, varying from 90% where the
      indication for primary CS was breech, 88% for fetal distress, and 55% for failure
      to progress. Forty percent of respondents agreed or strongly agreed that VBAC was
      the safest option for the woman, and associated with fewer risks than CS. In
      contrast, 44% of respondents disagreed or strongly disagreed that VBAC was the
      safest option for the infant, and opinions varied as to whether risks of VBAC
      outweighed those of CS for the infant. Almost two-thirds of practitioners would
      offer induction of labour to a woman with a prior CS in a subsequent pregnancy,
      one-third indicating a willingness to use vaginal prostaglandins, and 77%
      syntocinon. Most respondents preferred to conduct VBAC in a level two or three
      hospital (86%); required the availability within 30 min of an anaesthetist (81%),
      a neonatologist (84%), and operating theatre (97%); recommended continuous
      electronic fetal heart rate monitoring (86%); intravenous access (90%); and
      routine group and hold (79%) during labour. For an elective repeat CS, most
      practitioners request routine blood for group and hold (78%), a neonatologist in
      theatre (77%), the use of an in-dwelling urinary catheter (96%), and the use of
      intraoperative antibiotics (82%). CONCLUSIONS: Most obstetricians indicated VBAC
      to be the safest option for the woman, but were less certain about benefits and
      risks for the infant. The consensus of practice is to present VBAC as an option
      and induce labour if needed. Vaginal birth after Caesarean is preferred in a
      level two or three hospital, with an anaesthetist, neonatologist and operating
      theatre available within 30 min. The use of continuous electronic fetal heart
      rate monitoring and intravenous access are recommended. In planned CS, a
      neonatologist in theatre is preferred, and an in-dwelling urinary catheter an;!
      intraoperative antibiotics will be used.

PMID- 14712991
TI  - Interstitial ectopic pregnancy: a contemporary case series.

PMID- 14712992
TI  - Liver transplantation and pregnancy.

PMID- 14712993
TI  - Prolonged survival time following initial presentation with bony metastasis in
      stage IVb endometrial carcinoma.

PMID- 14712994
TI  - Positive pregnancy test in a patient with colorectal carcinoma.

PMID- 14712995
TI  - Severe post-partum haemorrhage of the right kidney.

PMID- 14712996
TI  - Intrapartum fetal death caused by embolisation of cerebral tissue to the heart
      and the lung.

PMID- 14712997
TI  - 'Conservative' management of placenta praevia percreta: report of two cases and
      discussion of current management options.

PMID- 14712998
TI  - Incarcerated procidentia due to cervical fibroid: an unusual presentation.

PMID- 14712999
TI  - Comment: 'A six-year audit of the management of ectopic pregnancy'.

PMID- 14713000
TI  - Gestational diabetes mellitus and maternal anxiety.

PMID- 14713001
TI  - Retained intrauterine clot following Caesarean section.

PMID- 14713002
TI  - Role of mucins in the function of the corneal and conjunctival epithelia.
AB  - The surface of the eye is covered by a tear film, which is held in place by a wet
      surfaced, stratified, corneal and conjunctival epithelia. Both are vital for
      light refraction and protection of vision. Maintenance of tear film on the ocular
      surface, lubrication, and provision of a pathogen barrier on this wet surface is
      facilitated by a class of large, highly glycosylated, hydrophilic glycoproteins-
      the mucins. In the past 15 years, a number of mucin genes have been cloned, and
      based on protein sequence, categorized as either secreted or membrane associated.
      Both types of mucins are expressed by ocular surface epithelia. Goblet cells
      intercalated within the stratified epithelium of the conjunctiva secrete the
      large gel-forming mucin MUC5AC, and lacrimal gland epithelia secrete the small
      soluble mucin MUC7. Apical cells of the stratified epithelium of both corneal and
      conjunctival epithelium express at least three membrane-associated mucins (MUCs
      1, 4, and 16), which extend from their apical surface to form the thick
      glycocalyx at the epithelium-tear film interface. The current hypothesis
      regarding mucin function and tear film structure is that the secreted mucins form
      a hydrophilic blanket that moves over the glycocalyx of the ocular surface to
      clear debris and pathogens. Mucins of the glycocalyx prevent cell-cell and cell
      pathogen adherence. The expression and glycosylation of mucins are altered in
      drying, keratinizing ocular surface diseases.

PMID- 14713003
TI  - Recent advances in the cell biology of polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial
      disorder, crossing multiple ethnicities as well as organ systems. The goal of
      understanding and, ultimately, curing ADPKD has fostered collaborative efforts
      among many laboratories, mustered on by the opportunity to probe fundamental
      cellular biology. Here we review what is known about ADPKD including well
      accepted data such as the identification of the causative genes and the fact that
      PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the
      "two-hit hypothesis," and somewhat confusing information regarding polycystin-1
      and -2 localization and protein interactions. Special attention is paid to the
      recently discovered role of the cilium in polycystic kidney disease and the model
      it suggests. Studying ADPKD is important, not only as an evaluation of a
      multisystem disorder that spans a lifetime, but as a testament to the
      achievements of modern biology and medicine.

PMID- 14713005
TI  - Regulatory pathways in lacrimal gland epithelium.
AB  - Tears are a complex fluid that continuously cover the exposed surface of the eye,
      namely the cornea and conjunctiva. Tears are secreted in response to the
      multitude of environmental stresses that can harm the ocular surface such as
      cold, mechanical stimulation, physical injury, noxious chemicals, as well as
      infections from various organisms. Tears also provide nutrients and remove waste
      from cells of the ocular surface. Because of the varied function of tears, tears
      are complex and are secreted by several different tissues. Tear secretion is
      under tight neural control allowing tears to respond rapidly to changing
      environmental conditions. The lacrimal gland is the main contributor to the
      aqueous portion of the tear film and the regulation of secretion from this gland
      has been well studied. Despite multiple redundencies in pathways to stimulate
      secretion from the lacrimal gland, defects can occur resulting in dry eye
      syndromes. These diseases can have deleterious effects on vision. In this review,
      we summarize the latest information regarding the regulatory pathways, which
      control secretion from the lacrimal gland, and their roles in the pathogenesis of
      dry eye syndromes.

PMID- 14713004
TI  - Estrogen receptors in the spinal cord, sensory ganglia, and pelvic autonomic
      ganglia.
AB  - Until relatively recently, most studies of the effects of estradiol in the
      nervous system focused on hypothalamic, limbic, and other brain centers involved
      in reproductive hormone output, feedback, and behaviors. Almost no studies
      addressed estradiol effects at the spinal cord or peripheral nervous system
      level. Prior to the mid-1960s-1970s, few studies examined neural components of
      reproductive endocrine organs (e.g., ovary or testis) or the genital organs
      (e.g., uterus or penis) because available data supported endocrine regulation of
      these structures. Over the last two decades interest in and studies on the
      innervation of the genital organs have burgeoned. Because of the responsiveness
      of genital organs to sex steroid hormones, these neural studies seeded interest
      in whether or not autonomic and sensory neurons that innervate these organs,
      along with their attendant spinal cord circuits, also are responsive to sex
      hormones. From the mid-1980s there has been a steady growth of interest in, and
      studies of the neuroanatomy, neurochemistry, neural connectivity, and neural
      functional aspects in reproductive organs and the response of these parameters to
      sex steroids. Thus, with the growth of probes and techniques, has come studies of
      anatomy, neurochemistry, and circuitry of sex hormone-responsive neurons and
      circuits in the spinal cord and peripheral nervous system. This review focuses on
      estrogen receptors in sensory, autonomic, and spinal cord neurons in locales that
      are associated with innervation of female reproductive organs.

PMID- 14713006
TI  - Regulation by RNA.
AB  - In recent years, noncoding RNAs (ncRNAs) have been shown to constitute key
      elements implicated in a number of regulatory mechanisms in the cell. They are
      present in bacteria and eukaryotes. The ncRNAs are involved in regulation of
      expression at both transcriptional and posttranscriptional levels, by mediating
      chromatin modifications, modulating transcription factor activity, and
      influencing mRNA stability, processing, and translation. Noncoding RNAs play a
      key role in genetic imprinting, dosage compensation of X-chromosome-linked genes,
      and many processes of differentiation and development.

PMID- 14713007
TI  - Some psychoanalytic perspectives on women.

PMID- 14713008
TI  - The femininization of the female oedipal complex, Part II: Aggression
      reconsidered.
AB  - This paper examines and explores the manifestations of aggressive impulses in the
      so-called female oedipal complex. The authors describe how competitive aggression
      on the part of young girls, seemingly missing in children's stories and myths, is
      unconsciously inhibited, disguised, or externalized. They report similar
      phenomena in women patients involved in triangular conflicts, and present a
      selected review of the literature on the inhibition of aggression within the
      female triangular situation. Stressing dynamic patterns in the object
      relationships in the female triangular situation, the authors offer a
      psychological explanation for this inhibition. They present clinical material to
      demonstrate how overt murderous and competitive aggression toward the mother
      appears after considerable analytic work. They conclude that girls and women
      frequently relinquish a sense of agency over both aggression and sexuality in
      dealing with triangular conflicts, to preserve a safe relationship with their
      mothers.

PMID- 14713009
TI  - The vanished pregnant body in psychoanalytic female developmental theory.
AB  - The author contends that the pregnant body-the premier icon of the mature female
      body-has vanished from our psychoanalytic theory of female development. Until we
      are able to restore this missing entity on a par with the phallus, the
      developmental theory for both sexes remains fixated in phallocentricism. The
      author traces some of the evidence for this claim in a brief overview of the
      literature, a study of the relevant aspects of the case of Little Hans, and a
      look at the history of medical teaching, in particular illustrations from the
      first dissections of female bodies in the sixteenth century, which demonstrate a
      view of the female body as essentially male. A puzzle remains about the marked
      tendencies that both males and females had, and still have, to distort the female
      body image. The author offers a clinical example, and the suggestion that the
      plasticity of the female form in all its developmental phases may underlie the
      paradoxical requirement that stable mental representations be established upon an
      elusive set of shifting images.

PMID- 14713010
TI  - "Too late": ambivalence about motherhood, choice, and time.
AB  - This paper explores a particular constellation of fantasies and defenses that in
      some women leads to the delay of childbearing. Destructive wishes towards the
      woman's own womb and her mother's lead to behaviors that sabotage fertility and
      pregnancy. These wishes and behaviors meet up with an unconscious belief in and
      commitment to time standing still, and with cultural tropes and trends that
      obscure intrapsychic conflicts and denials about motherhood, aging, and time.
      Analysis, like childbearing, is constrained by the reality of time, and the
      complex untangling and connecting of these three not obviously related threads
      may not occur until it is, for the woman who wants a child, too late.

PMID- 14713011
TI  - A fresh look at perversion.
AB  - The history of ideas about perversion is considered, along with an examination of
      whether the concept is clinically useful. Three cases of varying degrees of
      severity are presented, illustrating the clinical value of the concept in the
      analytic situation. All three cases are women, and the particular usefulness of
      the concept of perversion for women is noted. The place of aggression and the
      pleasure resulting from its expression are highlighted.

PMID- 14713012
TI  - Mothers' ambivalence with their babies and toddlers: manifestations of conflicts
      with aggression.
AB  - In this paper the author continues his study of conflicts over aggression in
      women, discussing the implications for contemporary theories of feminine
      psychology of observations of mothers in parent/child groups with their infants
      and toddlers. Many mothers experience conflicts over aggression (both in
      themselves and in their children) and become intolerant of their ambivalence
      toward their children. The author suggests that this observation provides an
      avenue that allows an integration of psychoanalytic ideas about maternity and
      childrearing with psychoanalytic understandings of women's conflicts about
      achievement in the social realm outside the home. In both roles, difficulties
      mastering conflicts with aggression may cause women to struggle profoundly, and
      to experience problems, in successfully negotiating their important life goals,
      whether the goals refer to their roles as effective mothers or their roles as
      effective individuals in the social sphere outside the home. Some women may
      demonstrate these difficulties in one sphere or the other, some in both, and
      others in neither. The author suggests on the one hand that we need to eliminate
      the concept of normality when considering the activities of women, and on the
      other hand that we need to normalize the omnipresence of ambivalence in the
      psychology of women.

PMID- 14713013
TI  - Cyclones, bi-cycles, and psychoanalysis: the witch-of-us? complex and The Wizard
      of Oz.
AB  - Works of applied psychoanalysis normally use psychoanalytic theory to reveal the
      secret meanings of works of art. An attempt is made to reverse the directionality
      of such analyses and see whether a work of art, The Wizard of Oz, has something
      to teach psychoanalysis about adolescent female psychosexual development. The
      author argues that the popularity and importance of the film is an effect of its
      symbolic representation of a girl's entry into menarche, and the meaning of this
      milestone for herself and for her mother. He addresses ideas about feminine
      castration fears (or what more recently have been called fears of genital
      injury), issues about menopause, and fantasies--both surprising and violent-
      around the meanings of menarche for both mother and daughter.

PMID- 14713014
TI  - Reading fiction and the psychoanalytic experience: Proust on reading and on
      reading Proust.
AB  - Reading can at times engage one emotionally and entail inner psychological
      experiences in ways akin to those in clinical psychoanalysis. In that light,
      after a general introduction regarding the import of reading, attention is turned
      to Proust, Freud's literary complement, as an exemplary instance to illustrate
      those similarities. Ideas of Proust on reading are followed by thoughts on
      reading Proust, with the ending of Proust's masterpiece used to illustrate a
      parallel to termination in clinical psychoanalytic experience.

PMID- 14713015
TI  - On the question of the patient's right to tell and the ethical reality of
      psychoanalysis.
AB  - This paper calls into question the view that it is ethically legitimate for the
      patient to say whatever comes to his or her mind: that is, to adhere to the
      fundamental rule. While there have been some variations in the application of
      this rule since Freud's time, it remains for many the bedrock of clinical
      practice, and the patient's right to free-associate has never been questioned.
      Recent debates on the importance of the analyst's strict confidentiality have
      highlighted this right. Ethical problems raised by adherence to the fundamental
      rule are explored through an examination of the general ethical limitations on
      what one may say to another person, and the special features of the analytic
      relationship that seem to do away with these limitations. The fact that there are
      ethical questions about adherence to the fundamental rule draws attention to what
      the author calls the ethical reality of psychoanalysis. The recognition of this
      reality has implications for the understanding and handling of ethical dilemmas
      regarding disclosure, as well as for other ethical issues that may arise in the
      course of an analysis.

PMID- 14713016
TI  - The daughter's seduction by her father is her enticement into the oedipal phase.

PMID- 14713017
TI  - Common and uncommon ground: a panel exchange.

PMID- 14713018
TI  - Is free association still fundamental? Panel report.

PMID- 14713019
TI  - Francoise Meltzer on Baudry's "Flaubert and Madame Bovary".

PMID- 14713020
TI  - The view from inside, the view from outside.

PMID- 14713021
TI  - Speciation of heavy metals in recent sediments of three coastal ecosystems in the
      Gulf of Cadiz, southwest Iberian Peninsula.
AB  - A live-step sequential extraction technique was used to determine the
      partitioning of Cr, Mn, Fe, Cu, Zn, Cd, and Pb among the operative sedimentary
      phases (exchangeable ions, carbonates, manganese and iron oxides, sulfides and
      organic matter. and residual minerals) in coastal sediment from three locations
      in the southwest Iberian Peninsula. Two sites are located close to industrial
      areas, the salt marshes of the Odiel River and Bay of Cadiz, and one in a
      nonindustrial area, the Barbate River salt marshes. The Odiel River salt marshes
      also receive the drainage from mining activities in the Huelva region. In the
      sediments from the Bay of Cadiz and Barbate River salt marshes, Cr, Cu, Fe, and
      Zn were extracted from the residual fraction at percentages higher than 60%. In
      the sediments from the Odiel River salt marshes, concentrations of all the
      metals, except Cu. Zn, and Cd, exceeded 60% in the residual fraction as well. In
      the sediments from the Bay of Cadiz and Barbate River salt marshes, the main
      bioavailable metals were Mn and Cd; in those from the Odiel River salt marshes,
      the main bioavailable metals were Zn and Cd, respectively. The environmental risk
      was determined by employing the environmental risk factor (ERF), defined as ERF =
      (CSQV - Ci/CSQV), where Ci is the heavy metal concentration in the first four
      fractions and CSQV is concentration sediment quality value (the highest
      concentration with no associated biological effect). Our results showed that the
      sediments from the Cadiz Bay and Barbate River salt marshes do not constitute any
      environmental risk under the current natural conditions. In contrast, in the
      Odiel River salt marshes, Cu, Zn, and Pb yielded ERFs of less than zero at
      several sampling stations and, consequently, pose a potential threat for the
      organisms in the area. This is a consequence of the high levels of metals in the
      area derived from the mining activity (pyrite) and industrial activities and the
      association of these heavy metals with more labile fractions of the sediments.

PMID- 14713022
TI  - Combination of microautoradiography and fluorescence in situ hybridization for
      identification of microorganisms degrading xenobiotic contaminants.
AB  - One of the central topics in environmental bioremediation research is to identify
      microorganisms that are capable of degrading the contaminants of interest. Here
      we report application of combined microautoradiography (MAR) and fluorescence in
      situ hybridization (FISH). The method has previously been used in a number of
      systems; however, here we demonstrate its feasibility in studying the degradation
      of xenobiotic compounds. With a model system (coculture of Pseudomonas putida B2
      and Sphingomonas stygia incubated with [14C] o-nitrophenol), combination of MAR
      and FISH was shown to be able to successfully identify the microorganisms
      degrading o-nitrophenol. Compared with the conventional techniques, MAR-FISH
      allows fast and accurate identification of the microorganisms involved in
      environmental contaminant degradation.

PMID- 14713023
TI  - The relationship between disinfection by-product formation and structural
      characteristics of humic substances in chloramination.
AB  - The influence of structural characteristics of humic substances on disinfection
      by-product (DBP) formation was investigated for seven humic substances isolated
      from aquatic and terrestrial sources. The structural characterizations included
      13C nuclear magnetic resonance (13C NMR) spectroscopy and ultraviolet (UV)
      spectroscopy. The aqueous humic substances were chloraminated at pH 7.0 and 8.5,
      with and without the presence of the bromide ion, and analyzed for total organic
      halogen (TOX), trihalomethanes (THMs), and haloacetic acids (HAAs). Aromatic
      contents determined by 13C NMR and differential UV absorbance at 254 nm
      statistically correlated with TOX formation for the humic substances investigated
      at p < 0.08. In contrast, a lack of correlation was observed for THM and HAA
      formation and these parameters. This paper also compiles relevant literature and
      discusses the contrasting reaction response of DBP precursor material to
      chlorination and chloramination.

PMID- 14713024
TI  - Assessment of bioavailability limitations during slurry biodegradation of
      petroleum hydrocarbons in aged soils.
AB  - In an effort to determine whether bioavailability limitations are responsible for
      the slow or incomplete hydrocarbon biodegradation in aged soils, both the rate of
      desorption (rdes) and biodegradation (rbio) was measured for n-alkanes and
      polynuclear aromatic hydrocarbons (PAHs) at different times during the slurry
      biotreatment of six different soils. While all n-alkanes were biodegraded to
      various degrees depending on their respective carbon number and the soil organic
      matter content, none of them were desorbed to a significant extent, indicating
      that these saturated hydrocarbons do not need to be transferred from the soil
      particles into the aqueous phase in order to be metabolized by microorganisms.
      Most two- and three-ring PAHs biodegraded as fast as they were desorbed (rbio =
      rdes); that is, desorption rates controlled biodegradation rates. By contrast,
      the biodegradation kinetics of four-, five-, and six-ring PAHs was limited by
      microbial factors during the initial phase (rbio < rdes) while becoming mass
      transfer rate limited during the final phase of bioremediation treatment (rbio =
      rdes). Whenever PAH biodegradation stalled or did not occur at all (rbio = 0), it
      was never due to bioavailability limitations (rdes >> 0) but was more likely
      caused by microbial factors. such as the absence of specific PAH degraders or
      cometabolic substrates. Consequently, PAHs that are found to be microbially
      recalcitrant in aged soils may not be so because of limited bioavailability and
      thus could pose a greater risk to the environment than previously thought.

PMID- 14713025
TI  - Investigating the role of desorption on the bioavailability of sediment
      associated 3,4,3',4'-tetrachlorobiphenyl in benthic invertebrates.
AB  - Only a fraction of all sediment-associated hydrophobic organic contaminants are
      bioavailable, and a simple Tenax extraction procedure may estimate this fraction.
      Bioavailability is assumed to coincide with the rapidly and, possibly, slowly
      desorbing sediment-associated contaminant. River sediment was spiked with
      radiolabeled (14C) and nonradiolabeled (12C) 3,4,3',4'-tetrachlorobiphenyl
      (TCBP), and desorption kinetics using Tenax extraction were obtained at 10
      degrees C and 22 degrees C. Bioaccumulation was measured in Lumbriculus
      variegatus, Chironomus tentans, and Hyalella azteca. Desorption of TCBP was
      triphasic at 22 degrees C and slowed at 10 degrees C to show only biphasic
      kinetics. The rapidly desorbing fractions decreased with increasing TCBP sediment
      concentration. The biota sediment accumulation factors, biota accumulation
      factors, and sediment clearance coefficients (ks) also decreased with increasing
      sediment TCBP concentration. The rapidly plus slowly desorbing fractions and the
      total TCBP desorbed when 99.9% of the rapidly desorbing fraction had desorbed
      were used to estimate bioavailable TCBP. These Tenax-based fractions did not
      explain the decreasing bioavailability with increasing TCBP load. Several
      factors, such as animal behavior and TCBP water solubility limitations, were
      evaluated to explain the concentration effect, but the most likely cause was
      severe diffusion limitations in whole sediment that were not predicted by the
      fully mixed Tenax extraction. Therefore, desorbing fractions determined by Tenax
      extraction overestimated the bioavailable fractions in sediments.

PMID- 14713026
TI  - Occurrence of neutral and acidic drugs in the effluents of Canadian sewage
      treatment plants.
AB  - Samples of influent (untreated) and effluent (treated) from 18 sewage treatment
      plants (STPs) in 14 municipalities in Canada were analyzed for residues of
      selected prescription and nonprescription drugs. Several neutral and acidic drugs
      were detected in effluents, including analgesic/anti-inflammatory agents, lipid
      regulators, and an antiepileptic drug, carbamazepine. Residues were extracted
      from effluents by solid-phase extraction, followed by either methylation and
      analysis of acidic drugs by gas chromatography/mass spectrometry or direct
      analysis of neutral drugs by liquid chromatography/tandem mass spectrometry.
      Analgesic/anti-inflammatory drugs such as ibuprofen and naproxen, as well as the
      metabolite of acetylsalicyclic acid, salicylic acid, were often detected in final
      effluents at microg/L concentrations. The acidic lipid regulator, clofibric acid,
      and the analgesic/anti-inflammatory drug diclofenac were not detected in any
      final effluent samples, which is not consistent with data from Europe. The
      precursor to clofibric acid, clofibrate, is not widely prescribed as a lipid
      regulator in Canada. However, the lipid regulators bezafibrate and gemfibrozil
      were detected in some samples of influent and effluent. The chemotherapy drugs
      ifosfamide and cyclophosphamide and the anti-inflammatory phenazone were not
      detected in influent or effluent samples, but the vasodilator drug pentoxyfylline
      was detected at ng/L concentrations in some final effluents. The widespread
      occurrence of carbamazepine at concentrations as high as 2.3 microg/L may be
      explained by use of this drug for other therapeutic purposes besides treatment of
      epilepsy and its resistance to elimination in STPs. The rates of elimination of
      ibuprofen and naproxen appeared to be elevated in STPs with hydraulic retention
      times for sewage greater than 12 h.

PMID- 14713027
TI  - Distribution of acidic and neutral drugs in surface waters near sewage treatment
      plants in the lower Great Lakes, Canada.
AB  - Prescription and nonprescription drugs have been detected in rivers and streams
      in Europe and the United States. Sewage treatment plants (STPs) are an important
      source of these contaminants, but few data exist on the spatial distribution of
      drugs in surface waters near STPs. Samples of surface water were collected in the
      summer and fall of 2000 at open-water sites in the lower Great Lakes (Lake
      Ontario and Lake Erie), at sites near the two STPs for the city of Windsor (ON,
      Canada), and at sites in Hamilton Harbour (ON, Canada), an embayment of western
      Lake Ontario that receives discharges from several STPs. In a follow-up study in
      the summer of 2002, samples of surface water and final effluent from adjacent
      STPs were collected from sites in Hamilton Harbour and Windsor. In addition,
      surface water and STP effluent samples were collected in Peterborough (ON,
      Canada). All samples of surface water and STP effluents were analyzed for
      selected acidic and neutral drugs. In the survey of Hamilton Harbour and Windsor
      conducted in 2000, acidic drugs and the antiepileptic drug carbamazepine were
      detected at ng/L concentrations at sites that were up to 500 m away from the STP,
      but the hydrological conditions of the receiving waters strongly influenced the
      spatial distribution of these compounds. Drugs were not detected at open-water
      locations in western Lake Erie or in the Niagara River near the municipality of
      Niagara-on-the-Lake (ON, Canada). However, clofibric acid, ketoprofen,
      fenoprofen, and carbamazepine were detected in samples collected in the summer of
      2000 at sites in Lake Ontario and at a site in the Niagara River (Fort Erie, ON,
      Canada) that were relatively remote from STP discharges. Follow-up studies in the
      summer of 2002 indicated that concentrations of acidic and neutral drugs in
      surface waters near the point of sewage discharge into the Little River (ON,
      Canada) STP were approximately equal to the concentrations in the final effluent
      from the STP. Caffeine and cotinine, a metabolite of nicotine, were generally
      present in STP effluents and surface waters contaminated by drugs. The
      antidepressant fluoxetine and the antibiotic trimethoprom were also detected in
      most STP effluents and some surface water samples. For the first time, the lipid
      regulating drug atorvastatin was detected in samples of STP effluent and surface
      water.

PMID- 14713028
TI  - Accumulation of ligands for aryl hydrocarbon and sex steroid receptors in fish
      exposed to treated effluent from a bleached sulfite/groundwood pulp and paper
      mill.
AB  - The accumulation of ligands for the aryl hydrocarbon receptor (AhR) and fish sex
      steroid receptors was investigated using two separate controlled fish exposures
      to final effluent from a bleached sulfite/groundwood mill in New Brunswick,
      Canada. In the first experiment, hepatic tissue extracts from exposed fish were
      fractionated according to lipophilicity. Fractions with different octanol-water
      (Kow) partition coefficients were tested for the presence of bioavailable
      chemicals that function as ligands for the AhR in H4IIE cells, rainbow trout
      hepatic estrogen receptors (ER), goldfish testicular androgen receptors (AR), and
      goldfish sex steroid binding protein (SSBP). Fish accumulated ligands for each
      receptor after 4-d exposure to effluent. Single fractions contained ligands for
      the AhR and the ER, while multiple fractions competed for the AR and SSBP. Fish
      also accumulated ligands for the AhR and SSBP from Saint John River dilution
      water, indicating upstream sources of bioactive substances. Semipermeable
      membrane devices deployed concurrently with fish accumulated ligands from
      effluent for all receptors except the ER. In the second experiment, accumulated
      ligands were evaluated after exposure of fish to effluent for two different
      durations and following a depuration period. Hepatic mixed function oxygenase
      activity and whole-liver hormonal activity, measured as binding to SSBP, returned
      to background following 6 d depuration and were reduced but still significant
      after 12-d exposure to effluent. Whole-liver extract affinities for the AR were
      maintained after extended exposure and depuration, indicating the potential for
      AR ligands to bioaccumulate. The accumulation of AhR ligands and ligands for sex
      steroid receptors provides a mechanistic linkage to effects on growth,
      development, and performance of fish exposed to effluent from this and other
      mills.

PMID- 14713029
TI  - Examination of the responses of slimy sculpin (Cottus cognatus) and white sucker
      (Catostomus commersoni) collected on the Saint John River (Canada) downstream of
      pulp mill, paper mill, and sewage discharges.
AB  - As part of a larger survey on cumulative effects within the Saint John River
      basin (Canada), a fish survey was conducted near Edmundston (NB, Canada) in the
      fall of 1999 using slimy sculpin (Cottus cognatus) and white sucker (Catostomus
      commersoni). The discharge environment receives effluent from the pulp mill, a
      paper mill, three sewage discharges, and tributaries receiving agricultural
      runoff. Sculpin collected downstream of the sewage discharges and pulp mill
      effluent had greater growth, condition, and liver size but no significant
      differences in gonad size. Stable isotope data indicated slimy sculpin did not
      move between sites. Female sculpin collected downstream of the paper mill showed
      no significant differences in length, body weight, age, condition factor, liver
      size, and gonad size compared to fish from reference sites. Female white sucker
      collected downstream of the pulp mill did not differ significantly in any
      measured parameter compared to reference fish. Liver sizes of white sucker from
      the Saint John River were outside the range considered to be indicative of
      uncontaminated riverine sites. In 2000, sculpin collected downstream from a
      poultry-processing facility had larger livers and lower condition factors,
      suggesting that the site is contaminated. We found no significant differences in
      sculpin length, weight, condition (except for males), and liver size in sculpin
      collected downstream from the pulp mill in October 2001. The responses of slimy
      sculpin and white sucker differed, perhaps in relation to differences in life
      history characteristics. Results from this study indicate the slimy sculpin is a
      suitable fish species for monitoring rivers that receive multiple industrial and
      municipal effluents.

PMID- 14713030
TI  - Changes in growth and secondary sex characteristics of fathead minnows exposed to
      bleached sulfite mill effluent.
AB  - Yellow perch captured downstream of a bleached sulfite mill had reduced gonad
      size and fecundity, and circulating steroid levels declined in goldfish exposed
      to final effluent for 21 d. To assess bleached sulfite mill (BSM) effluent, long
      term fathead minnow (Pimephales promelas) growth and reproduction tests were
      carried out in a flow-through bioassay trailer at the mill secondary treatment
      lagoons. Fertilized P. promelas eggs were hatched in effluent (0, 1, 3.2, 10, 32,
      50, and 100% final effluent with 10 ng/L ethinylestradiol as a positive control
      compound) and monitored through to 30, 60, and 125 d posthatch. The effluent
      caused a significant increase in the growth of fish; this effect was evident
      within 30 d. Fish had changes in secondary sex characteristics at maturity: Male
      fish had ovipositors in effluent concentrations as low as 3.2%. Higher effluent
      concentrations (32-100%) resulted in a majority of fish that looked externally
      like females. Changes in external sex characteristics were the most sensitive
      endocrine disruption-specific endpoints and required four months of exposure.
      Exposure to low BSM effluent concentrations (3.2%) resulted in female fish that
      had male sex characteristics (tubercles and dorsal fin dots). This
      masculinization of female fish was statistically significant at 10% effluent and
      was not seen in control fish. Concentrations of final effluent in the Saint John
      River (Canada) range from less than 1% to 15%, depending on the season and river
      flow. The research assesses some of the changes seen in fathead minnows exposed
      to this complex effluent, and demonstrates a threshold of <10% BSM effluent for
      the most sensitive effects.

PMID- 14713031
TI  - Effects of pulp mill effluent on benthic assemblages in mesocosms along the Saint
      John River, Canada.
AB  - We used mesocosms to examine the impact of different concentrations of pulp mill
      effluent (PME) on structural and functional endpoints of a benthic assemblage in
      the Saint John River (NB, Canada) during 1999 and 2000. Previous studies on this
      effluent's effects produced conflicting results, with field surveys suggesting a
      pattern of mild nutrient enrichment, while laboratory toxicity tests linked
      effluent exposure to moderate contaminant effects. Experimental treatments
      included three concentrations of sulfite pulp mill effluent (0, 5, 10% v/v PME).
      Endpoints for the assessment included algal biomass and taxonomic composition,
      benthic invertebrate abundance and composition, and insect emergence. Low
      concentrations of PME increased periphyton biomass and caused changes in
      community structure within the diatom-dominated community. Pulp mill effluent
      addition had little effect on several structural endpoints measured for benthic
      invertebrates, including abundance and taxonomic richness, but significantly
      changed community composition. For both periphyton and benthic invertebrates,
      community composition endpoints were more sensitive indicators of PME exposure.
      Insect emergence was a highly relevant functional endpoint. When benthic and
      emerged insects were combined, total abundance increased with PME addition.
      Results from two trophic levels, which provided multiple lines of evidence,
      indicated that the main impact of these PME concentrations is nutrient enrichment
      rather than effluent toxicity. Our findings also suggest that benthic
      invertebrate and periphyton assemblages, algal biomass production, and insect
      emergence are sensitive response measures. Future studies may confirm this
      observation. The consideration of both functional and structural endpoints at
      different trophic levels can greatly improve our understanding the effects of
      discharges to rivers. Such an understanding could not have been obtained using
      standard assessment techniques and illustrates the value of mesocosms and the
      benthic community assemblage approach in environmental assessment.

PMID- 14713032
TI  - Biomarker responses and chemical analyses in fish indicate leakage of polycyclic
      aromatic hydrocarbons and other compounds from car tire rubber.
AB  - Rubber tire material contains toxic compounds including oils rich in polycyclic
      aromatic hydrocarbons (PAH), so-called highly aromatic (HA) oils, as well as
      other reactive additives used as antioxidants, antiozonants, and vulcanization
      accelerators. The toxicity of rubber tire leachates to aquatic organisms has been
      demonstrated before. However, previous studies have focused on lethal rather than
      sublethal effects. We kept rainbow trout (Oncorhynchus mykiss) in tanks with two
      types of tires: a tire containing HA oils in the tread or a tire free of HA oils
      in the tread. After 1 d of exposure, an induction of cytochrome P4501A1 (CYP1A1)
      was evident in both exposed groups, measured as elevated ethoxyresorufin-O
      deethylase (EROD) activity and increased CYP1A1 mRNA levels. After two weeks of
      exposure, EROD activity and CYP1A1 mRNA were still high in fish exposed to
      leachate from HA oil-containing tire, whereas the effect was somewhat lower in
      fish exposed to leachate from HA oil-free tread tire. Compounds in the tire
      leachates also affected antioxidant parameters. Total glutathione concentration
      in liver as well as hepatic glutathione reductase, glutathione S-transferase, and
      glucose-6-phosphate dehydrogenase activities were markedly elevated after two
      weeks of exposure in both groups. The responses were greater in the group exposed
      to leachate from HA oil-free tread tire. Vitellogenin measurements did not
      indicate leakage of estrogenic compounds from the tires. Chemical analyses of
      bile from exposed fish revealed the presence of hydroxylated PAH as well as
      aromatic nitrogen compounds indicating uptake of these compounds by the fish.

PMID- 14713033
TI  - Influence of salinity on the bioaccumulation and photoinduced toxicity of
      fluoranthene to an estuarine shrimp and oligochaete.
AB  - The effect of salinity on the photoinduced toxicity of waterborne fluoranthene to
      larvae of the grass shrimp (Palaemonetes pugio) and tubificid oligochaete worms
      (Monopylephorus rubroniveus) was studied in a laboratory system under simulated
      sunlight. In the grass shrimp toxicity tests, five concentrations of fluoranthene
      (0, 3.6, 7.3, 13.8, and 29.0 microg/L) and four salinities (6.9, 14.5, 21.2, and
      28.6 per thousand) were achieved. In the oligochaete toxicity tests, five
      concentrations of fluoranthene (0, 0.8, 1.4, 3.3, and 7.7 microg/L) and four
      salinities (7.1, 13.3, 20.5, and 27.6 per thousand) were achieved. Salinity had
      no effect on either the photoinduced toxicity or the bioaccumulation of
      fluoranthene in the grass shrimp. However, the highest level of salinity
      decreased the median lethal time for the oligochaete. Bioaccumulation of
      fluoranthene was inversely related to salinity for the oligochaete. Additional
      experiments demonstrated an inverse relationship between salinity and short-term
      osmotic weight change in the oligochaete. Weight of the grass shrimp larvae was
      not affected by salinity. These findings show that salinity can influence the
      toxicity and bioaccumulation of fluoranthene in some estuarine organisms. The
      influence of salinity on these populations may be related to physiological
      responses associated with internal osmotic volume changes. Thus, salinity needs
      to be taken into account when assessing the risk of photoactivated polycyclic
      aromatic hydrocarbon (PAH) to at least some estuarine species.

PMID- 14713034
TI  - Toward detoxifying mercury-polluted aquatic sediments with rice genetically
      engineered for mercury resistance.
AB  - Mercury contamination of soil and water is a serious problem at many sites in the
      United States and throughout the world. Plant species expressing the bacterial
      mercuric reductase gene, merA, convert ionic mercury, Hg(II), from growth
      substrates to the less toxic metallic mercury, Hg(0). This activity confers
      mercury resistance to plants and removes mercury from the plant and substrates
      through volatilization. Our goal is to develop plants that intercept and remove
      Hg(II) from polluted aquatic systems before it can undergo bacterially mediated
      methylation to the neurotoxic methylmercury. Therefore, the merA gene under the
      control of a monocot promoter was introduced into Oryza sativa L. (rice) by
      particle gun bombardment. This is the first monocot and first wetland-adapted
      species to express the gene. The merA-expressing rice germinated and grew on
      semisolid growth medium spiked with sufficient Hg(II) to kill the nonengineered
      (wild-type) controls. To confirm that the resistance mechanism was the conversion
      of Hg(II) to Hg(0), seedlings of merA-expressing O. sativa were grown in Hg(II)
      spiked liquid medium or water-saturated soil media and were shown to volatilize
      significantly more Hg(0) than wild-type counterparts. Further genetic
      manipulation could yield plants with increased efficiency to extract soil Hg(II)
      and volatilize it as Hg(0) or with the novel ability to directly convert
      methylmercury to Hg(0).

PMID- 14713035
TI  - Sensitivity of water tupelo (Nyssa aquatica) and bald cypress (Taxodium
      distichum) seedlings to manganese enrichment under water-saturated conditions.
AB  - In anaerobic soils of wetlands, Mn is highly available to plants because of the
      decreasing redox potential and pH of flooded soil. When growing adjacent to each
      another in wetland forests, water tupelo (Nyssa aquatica L.) had 10 times greater
      leaf manganese concentration than bald cypress (Taxodium distichum [L.] Richard).
      This interspecific difference was examined over a range of manganese-enriched
      soil conditions in a greenhouse experiment. Water tupelo and bald cypress
      seedlings were grown in fertilized potting soil enriched with 0, 40, 80, 160,
      240, 320, and 400 mg Mn/L of soil and kept at saturated to slightly flooded
      conditions. Leaf Mn concentration was greater in water tupelo than bald cypress
      for all but the highest Mn addition treatment. Growth of water tupelo seedlings
      was adversely affected in treatments greater than 160 mg Mn/L. Total biomass of
      water tupelo in the highest Mn treatment was less than 50% of the control. At low
      levels of added Mn, bald cypress was able to restrict uptake of Mn at the roots
      with resulting low leaf Mn concentrations. Once that root restriction was
      exceeded, Mn concentration in bald cypress leaves increased greatly with
      treatment; that is, the highest treatment was 40 times greater than control
      (4,603 vs 100 microg/g, respectively), but biomass of bald cypress was unaffected
      by manganese additions. Bald cypress, a tree that does not naturally accumulate
      manganese, does so under manganese-enriched conditions and without biomass
      reduction in contrast to water tupelo, which is severely affected by higher soil
      Mn concentrations. Thus, bald cypress would be less affected by increased
      manganese availability in swamps receiving acidic inputs such as acid mine
      drainage, acid rain, or oxidization of pyritic soils.

PMID- 14713036
TI  - Establishing the impact of acid mine drainage through metal bioaccumulation and
      taxa richness of benthic insects in a tropical Asian stream (The Philippines).
AB  - The Boac-Makulapnit River (The Philippines) is contaminated with heavy metals
      primarily due to acid mine drainage (AMD). Heavy-metal levels in river water,
      sediment, and algae suggest that Cu is the primary contaminant in this system.
      Copper concentrations decrease longitudinally, indicating a contamination
      gradient away from the mine. This is also reflected in the whole-body metal
      concentration of the caddisfly Hydropsyche, wherein higher Cu levels are observed
      in upstream stations (677-980 microg/g in 2001). In 2002, AMD formation was
      observed in a midstream station resulting from the oxidation of mine tailings in
      floodplains deposited during a 1996 tailings spill event. This consequently
      increased heavy-metal concentrations locally in environmental media and is
      likewise perceived to have caused the absence of aquatic insects in the midstream
      reach. Copper concentrations also increased in Hydropsyche found downstream of
      the new AMD site during this year. Furthermore, even the lower Cu concentrations
      in Hydropsyche observed in downstream stations are still at least six times
      higher than the established regional baseline value (29.9 microg/g), which is
      calculated from samples from clean tributary streams. These tributary streams
      also showed higher taxa richness for aquatic insect community in riffle zones.
      Both biomonitoring tools suggest that the whole length of the river is severely
      impacted. Rehabilitation projects will be underway next year; therefore, such
      monitoring programs will truly be beneficial when gauging river habitat recovery.

PMID- 14713037
TI  - A comparative assessment of azinphosmethyl bioaccumulation and toxicity in two
      estuarine meiobenthic harpacticoid copepods.
AB  - Aqueous, pore-water, and whole-sediment bioassays were conducted with meiobenthic
      copepods with different infaunal lifestyles to assess the acute and chronic
      toxicity of the organophosphorous pesticide azinphosmethyl (APM) and its
      bioaccumulation potential in sediments. Biota sediment accumulation factors were
      an order of magnitude higher for the deeper burrowing Amphiascus tenuiremis
      (26.6) than the epibenthic Microarthridion littorale (2.2). The female A.
      tenuiremis APM median lethal concentration (LC50; 3.6 microg/L) was twice the
      male LC50 (1.8 microg/L), in straight seawater exposures, and nearly 20% higher
      than males in whole-sediment exposures (540 vs 456 ng/g dry weight). Amphiascus
      tenuiremis were 17 times more sensitive to sediment-associated APM than M.
      littorale. In pore-water-only exposures, the adult mixed-sex A. tenuiremis LC50
      (5.0 microg/L) was nearly twice the seawater mixed-sex LC50 (2.7 microg/L).
      Dissolved organic carbon in pore water was five times higher (20 mg/L) than in
      seawater-only exposures (4 mg/L). Differences in acute toxicity within exposure
      media were driven by species- and sex-specific differences in lipid content.
      Amphiascus tenuiremis likely experienced greater exposure to sediment-associated
      toxicants via longer periods of direct contact with pore water than M. littorale
      and, therefore, exhibited correspondingly higher bioaccumulation and acute
      toxicity. Copepod reproduction was significantly reduced (>60%) in 14-d sediment
      culture exposures at sublethal APM levels, suggesting that chronic field exposure
      to sediment-associated APM would result in sharp declines in copepod population
      growth.

PMID- 14713038
TI  - Constituents within pulp mill effluent deplete retinoid stores in white sucker
      and bind to rainbow trout retinoic acid receptors and retinoid X receptors.
AB  - Wild female and male white sucker (Catostomus commersoni) inhabiting an area
      receiving pulp mill effluent had reduced hepatic levels of retinol,
      didehydroretinol, retinyl esters, and didehydroretinyl esters, while vitamin E
      levels were unaffected. This disruption of the retinoid system led us to test
      methanol and dichloromethane extracts from the effluent of 11 pulp mills from
      across Canada for their ability to bind to rainbow trout (Oncorhynchus mykiss)
      retinoic acid receptors (RARs) from the gill and retinoid X receptors (RXRs) from
      the liver. Concentrated extracts of the final effluent from 6 of the 11 pulp
      mills were able to displace greater than 25% of the receptor-bound [3H]all-trans
      retinoic acid (RA) or [3H]9-cis RA from trout RARs and RXRs, respectively. The
      ability of the extracts to displace retinoic acid did not appear to be linked to
      the pulping or treatment processes. Moreover, extracts with the greatest activity
      came from thermomechanical mills, suggesting the compounds may originate from the
      wood furnish. In addition, extracts prepared from wood furnish (wood chips: white
      spruce [50%], lodgepole pine [47%], and balsam fir [3%]) from one mill were able
      to displace [3H]RA from the RARs and RXRs. The 4-hydroxy RA, a metabolite of RA
      that has been shown to be generated in greater quantities in fish exposed to P450
      inducing xenobiotics, was able to displace [3H]all-trans RA from trout RARs as
      effectively as unlabeled all-trans RA. These results suggest that pulp mill
      effluent may impact the retinoid system of fish at multiple sites, either by
      decreasing hepatic retinoid stores or through contributing additional ligands
      (from the wood furnish) that can bind to RA receptors.

PMID- 14713039
TI  - Biotransformation and genotoxicity of fluoranthene in the deposit-feeding
      polychaete Capitella sp. I.
AB  - Polycyclic aromatic hydrocarbons, such as fluoranthene (Flu), are of
      environmental concern because of their persistence, toxicity, and mutagenic
      properties. In this study we examined the genotoxicity of Flu to Capitella sp. I
      using the comet assay. We assessed patterns of DNA damage as a function of uptake
      route and as a function of exposure and depuration time and related levels of DNA
      damage to published information on Flu-metabolite formation. Exposure to
      approximately 30 microg Flu/g dry-weight sediment or 50 microg Flu/L seawater
      resulted in significant DNA damage. The degree of DNA damage was time dependent
      during both exposure and depuration, and although exposure route had no effect on
      the maximum degree of DNA damage occurring, it did influence the time course of
      damage. Levels of damage declined despite continued exposure to Flu, providing
      evidence for the induction of one or more DNA repair mechanisms. Comparison with
      Flu-metabolite profiles suggests that DNA damage is associated with the
      production of aqueous metabolites. The transitory nature of the DNA damage and
      repair process may contribute important insights into the mechanisms of toxicant
      effects at the molecular level but limits the usefulness of such endpoints as
      biomarkers of exposure or effect in ecotoxicological studies.

PMID- 14713040
TI  - Immunocompetence of juvenile chinook salmon against Listonella anguillarum
      following dietary exposure to polycyclic aromatic hydrocarbons.
AB  - Juvenile chinook salmon (Oncorhynchus tschawytscha) were fed a mixture of 14
      polycyclic aromatic hydrocarbon (PAH) compounds that reflected the PAH
      composition of salmon stomach contents in an urban estuary of Puget Sound,
      Washington (USA). Following a 28-d dietary exposure, a standardized Listonella
      anguillarum challenge model was used to determine whether PAH exposure (16, 64,
      and 252 mg/kg wet wt feed) causes reduced disease resistance under the conditions
      examined in this study. To assess innate immunity, five replicate groups of fish
      per dose were acclimated for one week, exposed to a lethal concentration 60 of
      bacteria, and monitored for 14 d. In a parallel experiment, the effects of PAH
      exposure on the acquired immune response were examined by immersion vaccinating
      fish against L. anguillarum and allowing specific immunity to develop for three
      weeks prior to challenge. All mortalities were aseptically sampled to confirm L.
      anguillarum infections. No significant differences in fish length, weight, or
      coefficient of condition were observed. These controlled laboratory experiments
      suggest that dietary exposures to an environmentally relevant mixture of PAH
      compounds do not alter the immunocompetence or growth of juvenile chinook salmon.

PMID- 14713041
TI  - Photoinduced lethal and sublethal toxicity of retene, a polycyclic aromatic
      hydrocarbon derived from resin acid, to coregonid larvae.
AB  - A comparative investigation on the acute phototoxicity of retene to vendace
      (Coregonus albula) and whitefish (C. lavaretus), both having pelagial larvae in
      spring, was conducted. To test the concept of early warning of sublethal
      biomarkers in relation to lethality to posthatch stages, we examined the effects
      of ultraviolet-B (UV-B) and retene on the levels of cytochrome P4501A (CYP1A) and
      heat shock protein 70 (HSP70) by exposing the animals to elevated levels of these
      factors for 48 and 72 h, respectively. Whereas UV-B and retene on their own were
      not lethal, simultaneous retene and UV-B exposure caused very high mortality to
      both species. The median lethal concentration (LC50; i.e., the concentration at
      which half of the larvae died) of retene as a precursor was 41 g/L for vendace
      and 15 to 16 microg/L, depending on the UV-B dose, for whitefish. Retene evoked
      substantial induction of CYP1A in larvae of both species, and UV-B induced CYP1A
      in whitefish. In vendace, no effect on HSP70 levels by any factor was observed.
      In whitefish, however, UV-B radiation and water retene alone upregulated HSP70,
      but no additive response was detected. The CYPIA is a biomarker of exposure to
      retene in both species. The HSP70 is an early warning signal of UV-B exposure in
      whitefish. As a species, vendace appears to be more resistant than whitefish to
      the phototoxicity of retene, as indicated by the higher tolerance.

PMID- 14713042
TI  - Dynamics of estrogen biomarker responses in rainbow trout exposed to 17beta
      estradiol and 17alpha-ethinylestradiol.
AB  - We have investigated the response dynamics of the estrogen-dependent genes
      vitellogenin (VTG) and the vitelline envelope proteins (VEPs) as well as
      circulating VTG in immature female rainbow trout (Oncorhynchus mykiss) exposed to
      17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) for periods of 7 and 14
      d. Gene responses were quantified by measurement of messenger RNA (mRNA) in liver
      extracts using a chemiluminescent hybridization protection assay. Circulating VTG
      was measured by a homologous enzyme-linked immunosorbent assay. Exposure to both
      E2 and EE2 induced concentration-dependent increases in all biomarkers. The data
      presented indicate that VEP genes may be more sensitive to estrogens than the VTG
      gene. The biomarker lowest-observed-effect concentrations (biomarkerLOEC) in the
      14-d study with E2 were 14 ng/L (VTG protein, VTG mRNA, VEPbeta, and VEPgamma) or
      4.8 ng/L (VEPalpha). The EE2 was 5- to 66-fold more potent depending on the
      biomarker studied. In the 7-d study, all biomarkers were elevated after 48-h
      exposure to E2, with biomarkerLOECs of 30 ng/L (VTG protein, VTG mRNA, and
      VEPgamma) or 9.7 ng/L (VEPalpha and VEPbeta). Vitellogenin mRNA was induced up to
      1,000-fold above baseline, and this translated into an increase of approximately
      50,000-fold in circulating VTG. In conclusion, all biomarkers responded to
      estrogen exposure at environmentally relevant concentrations.

PMID- 14713043
TI  - Reproductive and developmental effects of atrazine on the estuarine meiobenthic
      copepod Amphiascus tenuiremis.
AB  - Atrazine is one of the most widely used herbicides in the United States. Atrazine
      concentrations in coastal environments chronically range from 90 ng/L to 46
      microg/L, with rare but measured concentrations near 60 microg/L at edge-of-field
      conditions. Chronic atrazine effects on estuarine benthos exposed to
      environmentally relevant concentrations are unknown. The purpose of this research
      was to assess atrazine reproductive and developmental effects over multiple
      generation exposures of the copepod Amphiascus tenuiremis. Copepods were
      chronically exposed to two environmentally relevant nominal atrazine
      concentrations (2.5 and 25 microg/L, and to an environmentally unrealistic
      concentration (250 microg/L). Chronic exposures were performed using a 96-well
      microplate life cycle bioassay. Individual stage I copepodites (C1, n =
      60/treatment) were reared through two generations (F0 and F1) to sexual maturity
      and individually mated in microwells containing 200 microl of atrazine solution.
      Copepod survival across all treatments and generations was >95%. Atrazine did not
      affect development to reproductive maturity, time to egg extrusion, or time to
      egg hatch (p > 0.05). However, reproductive failures increased across generations
      with increasing atrazine concentrations. Reproductive failures in the 0-, 2.5-,
      25-, and 250-microg/L atrazine treatments were 11, 11, 20, and 24% for the F0 and
      4, 9, 26, and 38% for the F1, respectively. Compared to controls, total nauplii
      production per female was reduced by approximately 22% in F0 females exposed to
      250 microg/L atrazine (p < 0.05), and by approximately 23%, approximately 27%,
      and approximately 32% in F1 females exposed to 2.5-, 25-, and 250-microg/L
      atrazine treatments, respectively (p < 0.05). The combined effect of reproductive
      failure and reduced offspring production significantly reduced total population
      growth in the F1 generation (p < 0.05) even at atrazine concentrations lower than
      that considered safe for seawater chronic exposure (26 microg/L).

PMID- 14713044
TI  - Determining toxicity of lead and zinc runoff in soils: salinity effects on metal
      partitioning and on phytotoxicity.
AB  - When assessing cationic metal toxicity in soils, metals are often added to soil
      as the chloride, nitrate, or sulfate salts. In many studies, the effects of these
      anions are ignored or discounted; rarely are appropriate controls included. This
      study used five soils varying in pH, clay content, and organic matter to
      determine whether salinity from counter-ions contributed to or confounded metal
      phytotoxicity. Varying rates of Pb and Zn were applied to soils with or without a
      leaching treatment to remove the metal counter-ion (NO3-). Lactuca sativa
      (lettuce) plants were grown in metal-treated soils, and plant dry weights were
      used to determine median effective concentrations where there was a 50% reduction
      in yield (EC50s) on the basis of total metals measured in the soil after harvest.
      In two of the five soils, leaching increased the EC50s significantly for Zn by
      1.4- to 3.7-fold. In three of the five soils, leaching increased the EC50s
      significantly for Pb by 1.6- to 3.0-fold. The shift in EC50s was not a direct
      result of toxicity of the nitrate ion but was an indirect effect of the salinity
      increasing metal concentrations in soil solution and increasing its
      bioavailability for a given total metal concentration. In addition, calculation
      of potential salinity changes in toxicological studies from the addition of
      metals exhibiting strong sorption to soil suggested that if the anion associated
      with the metal is not leached from the soil, direct salinity responses could also
      lead to significant overestimation of the EC50 for those metals. These findings
      question the relevance of the application of single-metal salts to soils as a
      method of assessing metal phytotoxicity when, in many cases in our environment,
      Zn and Pb accumulate in soil over a period of time and the associated counter
      ions are commonly removed from the soil during the accumulation process (e.g..
      roof and galvanized tower runoff).

PMID- 14713045
TI  - Estrogenic compounds affect development of harpacticoid copepod Tigriopus
      japonicus.
AB  - The aim of this investigation was to evaluate the impact of estrogenic compounds
      on the harpacticoid copepod Tigriopus japonicus after continuous exposure to
      environmentally relevant concentrations. Natural estrogen (17beta-estradiol),
      three known estrogenic compounds in vertebrates (bisphenol A, 4-nonylphenol, p-t
      octylphenol), and an invertebrate molting hormone (20-hydroxyecdysone) were
      tested for their effects on development and reproductive characters in two
      successive generations of T. japonicus. Less than 24-h-old nauplii (parentals)
      were exposed to four sublethal concentrations of these compounds for 21 d at 25
      degrees C. The first brood of nauplii (F1) produced was monitored further under
      the same culture conditions and exposures to test compounds. Results showed that
      all estrogenic compounds affected development (both in number of days to reach
      copepodid stage and sexual maturity) in the parental generation. Similar effects
      were apparent in the F1; however, fecundity, sex ratio, and survival were not
      significantly affected, even at concentrations as high as 10 microg/L (nominal
      concentration). The invertebrate molting hormone 20-hyroxyecdysone had no
      detectable effect on any of the endpoints tested but gave the lowest 48-h 50%
      lethal concentration (LC50) value. The results suggest that endocrine disruption
      could occur in copepods following exposure to environmentally relevant
      concentrations of estrogenic compounds, especially if they are exposed starting
      from embryonic development.

PMID- 14713046
TI  - A strategy to reduce the numbers of fish used in acute ecotoxicity testing of
      pharmaceuticals.
AB  - The pharmaceutical industry gives high priority to animal welfare in the process
      of drug discovery and safety assessment. In the context of environmental
      assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and
      Drug Administration and draft European regulations may require testing of APIs
      for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data
      used to derive the predicted no-effect concentration [PNECwater] from the most
      sensitive of three species). Subject to regulatory approval, it is proposed that
      testing can be moved from fish median lethal concentration (LC50) testing
      (typically using > or = 42 fish/API) to acute threshold tests using fewer fish
      (typically 10 fish/API). To support this strategy, we have collated base-set
      ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial
      reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and
      daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for
      approximately 80% of these APIs, algal and daphnid acute EC50 data could have
      been used in the absence of fish LC50 data to derive PNECwater values. For the
      other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is
      predicted to give comparable PNECwater outcomes. Based on this preliminary
      scenario of 91 APIs, this approach is predicted to reduce the total number of
      fish used from 3,822 to 1,025 (approximately 73%). The present study, although
      preliminary, suggests that the current regulatory requirement for fish LC50 data
      regarding APIs should be succeeded by fish acute threshold (step-down) test data,
      thereby achieving significant animal welfare benefits with no loss of data for
      PNECwater estimates.

PMID- 14713047
TI  - Toxicity of mono- and diesters of o-phthalic esters to a crustacean, a green
      alga, and a bacterium.
AB  - The degradation of phthalic acid diesters may lead to formation of o-phthalic
      acid and phthalic acid monoesters. The ecotoxic properties of the monoesters have
      never been systematically investigated, and concern has been raised that these
      degradation products may be more toxic than the diesters. Therefore, the aquatic
      toxicity of phthalic acid, six monoesters, and five diesters of o-phthalic acid
      was tested in three standardized toxicity tests using the bacteria Vibrio
      fischeri, the green algae Pseudokirchneriella subcapitata, and the crustacean
      Daphnia magna. The monoesters tested were monomethyl, monoethyl, monobutyl,
      monobenzyl, mono(2-ethylhexyl), and monodecyl phthalate, while the diesters
      tested were dimethyl, diethyl, dibutyl, butylbentyl, and di(2
      ethylhexyl)phthalate, which were assumed to be below their water solubility. The
      median effective concentration (EC50) values for the three organisms ranged from
      103 mg/L to >4.710 mg/L for phthalic acid, and corresponding values for the
      monoesters ranged from 2.3 mg/L (monodecyl phthalate in bacteria test) to 4,130
      mg/L (monomethyl phthalate in bacteria test). Dimethyl and diethyl phthalate were
      found to be the least toxic of the diesters (EC50 26.2-377 mg/L), and the
      toxicity of the other diesters (butylbenzyl and dibutyl phthalate) ranged from
      0.96 to 7.74 mg/L. In general, the phthalate monoesters (degradation products)
      were less toxic than the corresponding diesters (mother compounds).

PMID- 14713048
TI  - Sublethal effects of Orimulsion-400 on eggs and larvae of Atlantic herring
      (Clupea harengus L.).
AB  - Orimulsion-400 is a novel bitumen-emulsion power plant fuel. We exposed Atlantic
      herring (Clupea harengus L.) eggs to 0, 0.1, 1.0, 10, 100, and 1,000 mg/L
      concentrations of an oil-in-water dispersion of Orimulsion-400 for a 24-h period.
      No significant differences were found in daily mortality or percent hatch. The
      1,000 mg/L exposure resulted in a significantly higher incidence of premature
      hatch, indicated by significantly shorter incubation time, significantly smaller
      total length and notochord length, and significantly greater yolk sac depth. The
      larvae exposed to the 1,000 mg/L treatment also had a significantly higher
      incidence of abnormalities than all other treatments.

PMID- 14713049
TI  - The effects of metals and food availability on the behavior of Caenorhabditis
      elegans.
AB  - Caenorhabditis elegans, a nonparasitic soil nematode, was used to assess the
      combined effects of metal exposures and food availability on behavior. Movement
      was monitored using a computer tracking system after exposures to Cu, Pb, or Cd
      while feeding was measured as a change in optical density (deltaOD) of bacteria
      suspensions over the exposure period. After 24-h exposures at high and low
      bacteria concentrations, movement was decreased in a concentration-dependent
      fashion by Pb and Cd but feeding reductions were not directly proportional to
      exposure concentrations. Copper exposure induced concentration-dependent declines
      in feeding and movement regardless of bacteria concentration. The impact of 24-h
      metal exposures was apparently reduced by increasing food availability.
      Therefore, exposures were shortened to 4 h in an attempt to minimize starvation
      effects on movement. Although nematodes were immobilized following 24 h of food
      depravation, worms deprived of food during the 4-h exposure continued to feed and
      move after exposure. A bead-ingestion assay after 4-h exposures was also used as
      an additional means of assessing the effects of metals on feeding behavior.
      Ingestion was significantly reduced by all concentrations of metals tested,
      indicating its sensitivity as a sublethal assay. Feeding (deltaOD) during
      exposures exhibited similar trends as ingestion but was slightly less sensitive,
      while movement was the least sensitive assay of 4-h metal exposures to C.
      elegans. Assessment of multiple sublethal endpoints allowed for the determination
      of the separate and interactive effects of metals and food availability on C.
      elegans behavior.

PMID- 14713050
TI  - Agricultural adjuvants: acute mortality and effects on population growth rate of
      Daphnia pulex after chronic exposure.
AB  - Acute and chronic toxicity of eight agricultural adjuvants (Bond, Kinetic, Plyac,
      R-11, Silwet L-77, Sylgard 309, X-77, and WaterMaxx) to Daphnia pulex were
      evaluated with 48-h acute lethal concentration estimates (LC50) and a 10-d
      population growth-rate measurement, the instantaneous rate of increase (r1).
      Based on LC50, the order of toxicity was R-11 > X-77 = Sylgard 309 = Silwet L-77
      > Kinetic > Bond > Plyac > WaterMaxx; all LC50 estimates were higher than the
      expected environmental concentration (EEC) of 0.79 mg/L, indicating that none of
      these adjuvants should cause high levels of mortality in wild D. pulex
      populations. Extinction, defined as negative population growth rate, occurred
      after exposure to 0.9 mg/L R-11, 13 mg/L X-77, 25 mg/L Kinetic, 28 mg/L Silwet,
      18 mg/L Sylgard, 450 mg/L Bond, 610 mg/L Plyac, and 1,600 mg/L WaterMaxx.
      Concentrations that caused extinction were substantially below the acute LC50 for
      R-11, Kinetic, Plyac, X-77, and Bond. The no-observable-effects concentration
      (NOEC) and lowest-observable-effects concentration (LOEC) for the number of
      offspring per surviving female after exposure to R-11 were 0.5 and 0.75 mg/L,
      respectively. The NOEC and LOEC for population size after exposure to R-11 were
      (1.25 and 0.5 mg/L, respectively. Both of these values were lower than the EEC,
      indicating that R-11 does have the potential to cause damage to D. pulex
      populations after application at recommended field rates. The wide range of
      concentrations causing extinction makes it difficult to generalize about the
      potential impacts that agricultural adjuvants might have on aquatic ecosystems.
      Therefore, additional studies that examine effects on other nontarget organisms
      and determine residues in aquatic ecosystems may be warranted.

PMID- 14713051
TI  - Toxicity of endosulfan to Atalophlebia spp. (Ephemeroptera) in the laboratory,
      mesocosm, and field.
AB  - A series of single-species toxicity tests was conducted in the laboratory and in
      outdoor stream mesocosms. The mayfly nymphs of Atalophlebia spp. (A. av2 and A.
      av6) were exposed to the organochlorine pesticide endosulfan for either 12- or 48
      h periods, with mortality recorded after 96 h. For both exposure periods, the
      lethal concentration (LC50 and LC 10) values were not significantly different
      between laboratory and mesocosm single-species tests, suggesting that the absence
      of natural environmental conditions and biological interactions in laboratory
      single-species tests did not influence the toxicity of technical endosulfan to
      Atalophlebia spp. Interpolation of toxicity test data indicates that peak
      endosulfan concentrations recorded in the rivers during storm events are likely
      to cause only minimal impact on Atalophlebia spp. populations. This suggests that
      changes in the abundance of populations observed in the field, if due to total
      endosulfan alone, are the result of chronic rather than acute exposure.

PMID- 14713052
TI  - Derivation of an ambient water quality criterion for mercury: taking account of
      site-specific conditions.
AB  - Mercury is considered to be a serious risk to wildlife. As a result, the Great
      Lakes Water Quality Initiative and others have developed ambient water quality
      criteria (AWQC) for the protection of wildlife. These AWQC have been
      controversial, however, because the AWQC were single values that did not account
      for site-specific conditions, derivation of the AWQC relied on a single no
      observed-adverse-effect level, and the AWQC had an unknown level of conservatism
      because of reliance on both average and conservative assumptions and uncertainty
      factors. Rather than develop a single-value AWQC for total mercury, we derived an
      AWQC model that explicitly incorporates factors controlling bioavailability,
      methylation rates, and bioaccumulation in the aquatic environment (e.g., pH,
      dissolved organic carbon). To derive our AWQC model, field data were collected
      from 31 lakes in Ontario and an additional 10 lakes in Nova Scotia (North
      America). In the field study, levels of total and methylmercury in water and fish
      as well as levels of key water quality variables were determined. We conducted
      multiple-regression analysis to derive a model that estimates mercury levels in
      prey of mink. Mink are very sensitive to mercury exposure. An independent dataset
      consisting of 51 water bodies in the United States was then used to confirm the
      validity and robustness of the AWQC model. Next, we combined the results of
      chronic-feeding studies with similar protocols and endpoints in a meta-analysis
      to derive a dose-response curve for mink exposed to mercury in the diet. In the
      final step, we used a probabilistic risk model to estimate the concentrations of
      methylmercury in water that would lead to levels in fish sufficient for a 10%
      probability of exceeding the lethal dose affecting 5% of the mink population. The
      result is an AWQC equation for mercury for the protection of wildlife that can be
      used with a variety of site-specific conditions.

PMID- 14713053
TI  - Issues of replicability in Monte Carlo modeling: a case study with a pesticide
      leaching model.
AB  - Sensitivity and uncertainty analyses based on Monte Carlo sampling were
      undertaken for various numbers of runs of the pesticide leaching model (PELMO).
      Analyses were repeated 10 times with different seed numbers. The ranking of PELMO
      input parameters according to their influence on predictions for leaching was
      stable for the most influential parameters. For less influential parameters, the
      sensitivity ranking was severely influenced by the seed number used. For
      uncertainty analyses, probabilities of exceeding a particular concentration were
      significantly influenced by the seed number used in the random sampling of values
      for the two parameters considered, even for those cases in which 5,000 model runs
      were undertaken (coefficient of variation of 10 replicated analyses, 5%). A
      decrease in the variability of exceedance probabilities could be achieved by
      further increasing the number of model runs. However, this may prove to be
      impractical when complex deterministic models with a relatively long running time
      are used. Attention should be paid to replicability aspects by modelers when
      devising their approach to assessing the uncertainty associated with the modeling
      and by decision makers when examining the results of probabilistic approaches.

PMID- 14713054
TI  - Statistical analysis of honeybee survival after chronic exposure to insecticides.
AB  - Studies concerning long-term survival of honeybees raise the problem of the
      statistical analysis of mortality data. In the present study, we used a modeling
      approach of survival data of caged bees under chronic exposure to two pesticides
      (imidacloprid and deltamethrin). Our model, based on a Cox proportional hazard
      model, is not restricted to a specific hazard functional form, such as in
      parametric approaches, but takes into account multiple covariates. We consider
      not only the pesticide treatment but also a nuisance variable (variability
      between replicates). Moreover, considering the occurrence of social interactions,
      the model integrates the fact that bees do not die independently of each other.
      We demonstrate the chronic toxicity induced by imidacloprid and deltamethrin. Our
      results also underline the role of the replicate effect, the density-dependent
      effect, and their interactions with the treatment effect. None of these
      parameters can be neglected in the assessment of chronic toxicity of pesticides
      to the honeybee.

PMID- 14713055
TI  - Seriously emotionally disturbed youth: a needs assessment.
AB  - A desire to improve outcomes for children and families led Erie County, New York
      to collaborate with the University at Buffalo Department of Family Medicine on a
      needs assessment of children with emotional disturbance. Demographic and
      behavioral characteristics, as well as service needs were identified through case
      based interviews conducted with key informants who provided services to children
      with emotional disturbance. Family interviews were conducted whenever possible.
      Results demonstrate a need for enhanced case management, service coordination,
      services specific to children and families, and expanded community-based
      services.

PMID- 14713056
TI  - Religion and spirituality in the lives of people with serious mental illness.
AB  - Although there is a fair sized literature documenting the relationship of
      religiousness and spirituality with health and well-being, far fewer studies have
      examined this phenomenon for people with serious mental illness. In this
      research, religiousness is defined as participation in an institutionalized
      doctrine while spirituality is framed as an individual pursuit of meaning outside
      the world of immediate experience. In this study, 1,824 people with serious
      mental illness completed self-report measures of religiousness and spirituality.
      They also completed measures of three health outcome domains: self-perceived well
      being, psychiatric symptoms, and life goal achievement. Results showed that both
      religiousness and spirituality were significantly associated with proxies of well
      being and symptoms, but not of goal achievement. Implications of these findings
      for enhancing the lives of people with psychiatric disability are discussed.

PMID- 14713057
TI  - How managed care has affected mental health case management activities,
      caseloads, and tenure.
AB  - The purpose of this study was to identify changes in case management within
      public sector mental health, following the implementation of managed care. Case
      managers in the State of Oregon completed surveys in 1992 and 2000 regarding
      aspects of case management. Results showed that current case managers are more
      experienced and expect longer tenure than previously. Caseload sizes have
      increased. Meanwhile, case managers' activities and functions have not changed
      across time periods. The results suggest that mental health personnel have
      changed in the past decade, though the practice of case management has remained
      largely the same.

PMID- 14713058
TI  - The Kansas Excellence in Client-Centered Supervision Program: design and initial
      results.
AB  - Supervisors in community support services are perceived as important to the
      performance of their teams or programs. Research on training as a means of
      improving skills has been discouraging. This paper describes a program designed
      to improve outcomes by providing multiple supports, including training, to CSS
      supervisors. Results after one year of operation are reported.

PMID- 14713059
TI  - Patients with HIV infection and mental illness: a study of clinical
      identification.
AB  - We compared provider diagnosis of mental illness as noted in a chart audit to an
      indication of mental illness using the Revised Symptom Checklist (SCL-90R). We
      identified cases of correct diagnoses, over-diagnoses, and missed diagnoses of
      mental illness by examining mental functioning (using the SF-36). Providers over
      diagnosed mental illness in 23% of the cases and missed a diagnosis in 9% of the
      cases. The over-diagnosed group had significantly better mental functioning and
      the missed-diagnosis group did not have better mental functioning than those who
      the provider and SCL-90 agreed had mental illness. The SCL-90R had a higher
      correlation with mental functioning than did the providers' diagnoses, suggesting
      that such instruments may increase the correct detection of mental illness in the
      HIV population.

PMID- 14713060
TI  - The effect of psychiatric rehabilitation on the activity and participation level
      of clients with long-term psychiatric disabilities.
AB  - During the last decades of the 20th century, many psychiatric hospitals changed
      the living environments of their clients with long-term psychiatric disabilities.
      We investigated the effect of this environmental psychiatric rehabilitation and
      normalization process on the activity and participation level of such clients
      residing in one Dutch psychiatric hospital. The seven years of panel research
      demonstrated that more normal living environments have a positive effect on
      clients' activity and participation level. This is controlled for the fact that
      younger clients, and clients with a relative high activity and participation
      level were selected for these normal living environments.

PMID- 14713062
TI  - The Ten Commandments.

PMID- 14713061
TI  - Assessing conformance to medication treatment guidelines for schizophrenia in a
      community mental health center (CMHC).
AB  - The feasibility of implementing current medication treatment guidelines in a
      community mental health clinic was examined in this cross-sectional and
      retrospective study. Specifically, two issues were addressed: 1) could we
      identify a set of clinical guidelines whose utilization could be monitored with a
      routine medical chart review; and 2) were the requisite data for such a review
      available in the medical records. An examination of three sets of published
      guidelines revealed 5 specific guidelines that could be operationalized and
      monitored. Records were reviewed for a random sample of two-thirds of all
      patients currently diagnosed with schizophrenia and schizoaffective disorder (n =
      309). Information was collected from the medical record on patient demographics,
      diagnosis, duration of illness, symptoms and side effects, and medication
      information. Rates of conformance to the 5 guidelines ranged from a high of 97%
      to a low of 43%. The use of current guidelines to improve treatment in community
      clinics appears to be limited by the deficiencies in the medical record and the
      structure of the guidelines themselves. Standardized progress notes and
      computerized prescribing programs will improve conformance, and permit the rapid
      and accurate assessment of conformance to guidelines in community clinics.

PMID- 14713063
TI  - Ingrowth of bone into absorbable bone cement: an in vivo microscopic evaluation.
AB  - The purpose of the study reported here was to use an in vivo rabbit model to
      evaluate the rate of bone ingrowth into remodelable calcium phosphate bone
      cement. We evaluated an in vivo bone chamber placed in a rabbit tibia with its
      ingrowth compartment filled with absorbable calcium phosphate bone cement (Norian
      Skeletal Repair System; Norian Corp, Cupertino, Calif). Five New England white
      rabbits had a single bone chamber implanted into the proximal right tibia.
      Observations were made and photomicrographs taken on a weekly basis. Results of
      morphological analysis showed sequential loss of cement and subsequent bone
      ingrowth over a testing period of up to 30 weeks. Resorption of bone cement was
      complete in 1 rabbit. The other rabbits had significant bone ingrowth, which
      reaffirms the biocompatibility of this material. Results of this study showed
      that using in vivo microscopy with the rabbit bone chamber model was useful in
      evaluating bone ingrowth and replacement of absorbable bone cement. This model
      may make it possible to evaluate various combinations of bone cement and bone
      growth factors, which could serve as an alternative to autogenous bone grafting.

PMID- 14713064
TI  - A cohort study of systemic and local complications of toe prostheses.
AB  - We investigated the role of toe implants in systemic disease and evaluated local
      complications after foot surgery. Information was obtained from the medical
      records of Kaiser Permanente (northern California) patients who had undergone toe
      surgery between 1979 and 1988. Computerized hospitalization records were used to
      identify patients with toe implants (N=814) and matched controls with foot
      surgery not involving implants (N=837). Brain cancer and alopecia areata occurred
      more among implant patients, whereas dysphagia occurred more among nonimplant
      patients. A larger proportion of implant patients were diagnosed with pain and
      swelling, tendonitis, and osteomyelitis or periostitis. Nonimplant patients were
      more often diagnosed with derangement of foot or ankle and delayed postoperative
      healing. We did not find a general association between implants and connective
      tissue diseases.

PMID- 14713065
TI  - Total knee arthroplasty in a patient with quadriceps paralysis secondary to
      poliomyelitis: a case report.
AB  - Degenerative joint disease is known to occur in patients with a history of polio.
      However, minimal or absent quadriceps function is generally considered to be a
      contraindication to total knee arthroplasty. We describe an elderly patient with
      quadriceps paralysis secondary to poliomyelitis who underwent a successful total
      knee replacement for severe osteoarthritis. The primary operative indication was
      disabling pain. At the 1-year follow-up the patient reported excellent pain
      relief, and there were no clinical or radiographic signs of deformity.

PMID- 14713066
TI  - Lateral subtalar dislocation in a 19-month-old female.
AB  - We report a lateral subtalar dislocation in a female 19-month-old after a minor
      fall. Review of the literature reveals no prior report of this injury in a
      patient of this age. This case illustrates the importance of thoroughly examining
      the pediatric patient. When fracture is not diagnosed and a child refuses to use
      the affected extremity, examination to rule out occult fracture or dislocation
      must be included.

PMID- 14713067
TI  - Luxatio erecta (inferior dislocation of the shoulder): a report of 5 cases and a
      review of the literature.
AB  - Luxatio erecta (inferior dislocation of the glenohumeral joint) is an unusual
      type of shoulder dislocation. The authors present 5 new cases of luxatio erecta.
      All cases were hyperabduction injuries. In all cases, closed reduction was
      accomplished by a traction-countertraction maneuver. Three of the 5 subjects
      sustained concomitant fractures of the greater tuberosity. One underwent open
      reduction and internal fixation of the greater tuberosity. One suffered axillary
      nerve injuries. No vascular injuries were noted in our series. The mechanism of
      the injury is discussed.

PMID- 14713068
TI  - Combined physeal/apophyseal fracture of the proximal tibia with anterior
      angulation from an indirect force: report of 2 cases.
AB  - Physeal fracture of the proximal tibia is a rare injury, comprising less than 2%
      of all physeal injuries. The literature distinguishes between tibial tubercle
      avulsions (apophyseal injuries) classified by Ogden, Tross, and Murphy as type I,
      II, and III and Salter-Harris II fractures. An extensive review of the literature
      located only 5 cases in which patients sustained a combined fracture of the
      proximal tibial physis and tibial tubercle. We report 2 such cases, which are not
      amenable to classification by current systems, and agree with Ryu and Debenham's
      suggestion to add a fourth type, avulsion hinge fracture of the proximal tibial
      epiphysis, to the Watson-Jones/Ogden classification.

PMID- 14713069
TI  - All medical physicists entering the field should have a specific course on
      research and practice ethics in their educational background. For the
      proposition.

PMID- 14713070
TI  - All medical physicists entering the field should have a specific course on
      research and practice ethics in their educational background. Against the
      proposition.

PMID- 14713071
TI  - A phantom study on the positioning accuracy of the Novalis Body system.
AB  - A phantom study was conducted to investigate inherent positioning accuracy of an
      image-guided patient positioning system-the Novalis Body system for three
      dimensional (3-D) conformal radiotherapy. This positioning system consists of two
      infrared (IR) cameras and one video camera and two kV x-ray imaging devices. The
      initial patient setup was guided by the IR camera system and the target
      localization was accomplished using the kV x-ray imaging system. In this study,
      the IR marker shift and phantom rotation were simulated and their effects on the
      positioning accuracy were examined by a Rando phantom. The effects of CT slice
      thickness and treatment sites on the positioning accuracy were tested. In
      addition, the internal target shift was simulated and its effect on the
      positioning accuracy was examined by a water tank. With the application of the
      Novalis Body system, the positioning error of the planned isocenter was
      significantly reduced. The experimental results with the simulated IR marker
      shifts indicated that the positioning errors of the planned isocenter were 0.6 +/
      0.3, 0.5 +/- 0.2, and 0.7 +/- 0.2 mm along the lateral, longitudinal, and
      vertical axes, respectively. The experimental results with the simulated phantom
      rotations indicated that the positioning errors of the planned isocenter were 0.6
      +/- 0.3, 0.7 +/- 0.2, and 0.5 +/- 0.2 mm along the three axes, respectively. The
      experimental results with the simulated target shifts indicated that the
      positioning errors of the planned isocenter were 0.6 +/- 0.3, 0.7 +/- 0.2, and
      0.5 +/- 0.2 mm along the three axes, respectively. On average, the positioning
      accuracy of 1 mm for the planned isocenter was achieved using the Novalis Body
      system.

PMID- 14713072
TI  - Effects of quantum noise and binocular summation on dose requirements in
      stereoradiography.
AB  - In the case of a quantum-noise limited detector, signal detection theory suggests
      that stereoradiographic images can be acquired with one half of the per-image
      dose needed for a standard radiographic projection, as information from the two
      stereo images can be combined. Previously, film-screen stereoradiography has been
      performed using the same per-image dose as in projection radiography, i.e.,
      doubling the total dose. In this paper, the assumption of a possible decrease in
      dose for stereoradiography was tested by a series of contrast-detail experiments,
      using phantom images acquired over a range of exposures. The number of visible
      details, the effective reduction of the dose, and the effective decrease in the
      threshold signal-to-noise ratio were determined using human observers under
      several display and viewing conditions. These results were averaged over five
      observers and compared with multiple readings by a single observer and with the
      results of an additional observer with limited stereoscopic acuity. Experimental
      results show that the total dose needed to produce a stereoradiographic image
      pair is approximately 1.1 times the dose needed for a single projection in
      standard radiography, indicating that under these conditions the human visual
      system demonstrates almost ideal binocular summation.

PMID- 14713073
TI  - Adaptive temporal resolution optimization in helical cardiac cone beam CT
      reconstruction.
AB  - Cone beam computed tomography scanners in combination with heart rate adaptive
      reconstruction schemes have the potential to enable cardiac volumetric computed
      tomography (CT) imaging for a larger number of patients and applications. In this
      publication, an adaptive scheme for the automatic and patient-specific
      reconstruction optimization is introduced to improve the temporal resolution and
      image quality. The optimization method permits the automatic determination of the
      required amount of gated helical cone beam projection data for the reconstruction
      volume. It furthermore allows one to optimize subvolume reconstruction yielding
      an increased temporal resolution. In addition, methods for the assessment of the
      temporal resolution are given which enable a quantitative documentation of the
      reconstruction improvements. Results are presented for patient data sets acquired
      in low pitch helical mode using a 16-slice cone beam CT system with parallel ECG
      recording.

PMID- 14713074
TI  - Computer-aided diagnosis in high resolution CT of the lungs.
AB  - A computer-aided diagnosis (CAD) system is presented to automatically distinguish
      normal from abnormal tissue in high-resolution CT chest scans acquired during
      daily clinical practice. From high-resolution computed tomography scans of 116
      patients, 657 regions of interest are extracted that are to be classified as
      displaying either normal or abnormal lung tissue. A principled texture analysis
      approach is used, extracting features to describe local image structure by means
      of a multi-scale filter bank. The use of various classifiers and feature subsets
      is compared and results are evaluated with ROC analysis. Performance of the
      system is shown to approach that of two expert radiologists in diagnosing the
      local regions of interest, with an area under the ROC curve of 0.862 for the CAD
      scheme versus 0.877 and 0.893 for the radiologists.

PMID- 14713075
TI  - Surface and build-up region dosimetry for obliquely incident intensity modulated
      radiotherapy 6 MV x rays.
AB  - This study investigates the surface dose and build-up region dosimetry for
      oblique IMRT beams. The dependence of surface and build-up region doses of 0
      degrees (perpendicular incidence) and 75 degrees (oblique incidence) IMRT fields
      on field size was measured and compared with open field dosimetry. Measurements
      were performed using a parallel-plate chamber and KODAK EDR2 films in a
      polystyrene phantom for a 6 cm x 6 cm and a 12 cm x 12 cm, 6 MV photon beam at
      depths of 0 mm (surface) through dmax. Data were normalized to the dmax value of
      each field. Four intensity modulated delivery patterns were created and delivered
      using step-and-shoot IMRT: (1) six static 1 cm x 6 cm strips (IMRTstrip), (2) 12
      static 1 cm x 12 cm strips (IMRTstrip), (3) intensity modulated beam patterns
      created by using the inverse planning optimization software (IMRTopt) for 6 cm x
      6 cm, and (4) IMRTopt for 12 cm x 12 cm field sizes. The percent depth doses
      (PDDs) of 0 degrees, 6 cm x 6 cm IMRTstrip beam at the surface and 5 mm were
      lower by 8.8% and 1.6%, respectively, compared to the open field. The PDDs of 75
      degrees, 6 cm x 6 cm IMRTstrip beam at the surface and 5 mm were lower by 6.7%
      and 2.4%, respectively, compared to the open field. This study showed that IMRT
      itself is not contributing to greater skin doses.

PMID- 14713076
TI  - Clinical helical tomotherapy commissioning dosimetry.
AB  - Helical tomotherapy presented many unique dosimetric challenges and solutions
      during the initial commissioning process, and some of them are presented. The
      dose calculation algorithm is convolution/superposition based. This requires that
      the energy fluence spectrum and magnitude be quantified. The methodology for
      doing so is described. Aspects of the energy fluence characterization that are
      unique to tomotherapy are highlighted. Many beam characteristics can be measured
      automatically by an included megavoltage computed tomography imaging system. This
      greatly improves data collection efficiency.

PMID- 14713077
TI  - Monte Carlo model of the Studsvik BNCT clinical beam: description and validation.
AB  - The neutron beam at the Studsvik facility for boron neutron capture therapy
      (BNCT) and the validation of the related computational model developed for the
      MCNP-4B Monte Carlo code are presented. Several measurements performed at the
      epithermal neutron port used for clinical trials have been made in order to
      validate the Monte Carlo computational model. The good general agreement between
      the MCNP calculations and the experimental results has provided an adequate check
      of the calculation procedure. In particular, at the nominal reactor power of 1
      MW, the calculated in-air epithermal neutron flux in the energy interval between
      0.4 eV-10 keV is 3.24 x 10(9) n cm(-2) s(-1) (+/- 1.2% 1 std. dev.) while the
      measured value is 3.30 x 10(9) n cm(-20 s(-1) (+/- 5.0% 1 std. dev.).
      Furthermore, the calculated in-phantom thermal neutron flux, equal to 6.43 x
      10(9) n cm(-2) s(-1) (+/- 1.0% 1 std. dev.), and the corresponding measured value
      of 6.33 X 10(9) n cm(-2) s(-1) (+/- 5.3% 1 std. dev.) agree within their
      respective uncertainties. The only statistically significant disagreement is a
      discrepancy of 39% between the MCNP calculations of the in-air photon kerma and
      the corresponding experimental value. Despite this, a quite acceptable overall in
      phantom beam performance was obtained, with a maximum value of the therapeutic
      ratio (the ratio between the local tumor dose and the maximum healthy tissue
      dose) equal to 6.7. The described MCNP model of the Studsvik facility has been
      deemed adequate to evaluate further improvements in the beam design as well as to
      plan experimental work.

PMID- 14713078
TI  - In vivo diode dosimetry for routine quality assurance in IMRT.
AB  - Due to the complexity of IMRT dosimetry, dose delivery evaluation is generally
      done using a treatment plan in which the optimized fluence distribution has been
      transferred to a test phantom for accessibility and simplicity of measurement.
      The actual patient doses may be reconstructed in vivo through the use of
      electronic portal imaging devices or films, but the assessment of absolute dose
      from these measurements is time-consuming and complicated. In our clinic we have
      instituted the use of routine diode dosimetry for IMRT patients following the
      same procedure used for standard radiation therapy patients in which each new
      treatment field is checked at the start of treatment. For standard cases the dose
      at dmax is calculated as part of the monitor unit calculation. For the IMRT
      cases, the dose contribution to the dmax depth for each field is taken from the
      treatment plan. We found that about 90% of the diode measurements agreed to
      within +/- 10% of the planned doses (45/51 fields) and 63% (32/51 fields)
      achieved +/- 5% agreement. By using this direct in vivo method to verify the
      clinical doses delivered, we have been able to make a uniform startup procedure
      for all patients while simplifying our IMRT QA process.

PMID- 14713079
TI  - Commissioning 6 MV photon beams of a stereotactic radiosurgery system for Monte
      Carlo treatment planning.
AB  - The goal of this work is to implement a beam commissioning procedure to generate
      a multiple source model using a set of standard measurement data for possible
      Monte Carlo treatment planning in the clinic for a Cyberknife stereotactic
      radiosurgery system. The required measurement data include the central axis depth
      dose curve (PDD), the dose profile at dmax(= 1.5 cm) of 60 mm cone at 80 cm
      source-to-surface distance (SSD), and the cone output factors for cones of 5 mm
      to 60 mm at 80 cm source-to-axis distance (SAD). The employed dual source model
      has the same structure as the one that has been studied in our previous work
      while most of the parameters of each source are extracted from the measurement
      data rather than the beam phase space. The energy spectra will be extracted from
      the central axis PDD, the fluence distributions will be deconvoluted from the
      dose profile at dmax, and the source distributions will be determined from the
      measured cone output factors. Monte Carlo dose calculations in various water
      phantoms have been performed to verify the beam commissioning procedure. The
      agreement between the measurements and the commissioning results was within 2%/1
      mm for the central axis PDDs and the dose profiles at various depths when an IC-3
      chamber was used and within 2% for the cone output factors for various collimator
      sizes of 5 to 60 mm. Largest difference (9.5%) was observed for the 7.5 mm cone
      when an IC-10 chamber was used. The large differences can be attributed to the
      volumetric averaging effect of the IC-10 chamber, whose dimension is comparable
      to the field of the small cones. The overall agreement between the measurements
      and the commissioning results is clinically acceptable, which implies that our
      commissioning tool is adequate for clinical applications of Monte Carlo dose
      calculations for the Cyberknife stereotactic radiosurgery system.

PMID- 14713081
TI  - Dosimetric IMRT verification with a flat-panel EPID.
AB  - A convolution-based calibration procedure has been developed to use an amorphous
      silicon flat-panel electronic portal imaging device (EPID) for accurate
      dosimetric verification of intensity-modulated radiotherapy (IMRT) treatments.
      Raw EPID images were deconvolved to accurate, high-resolution 2-D distributions
      of primary fluence using a scatter kernel composed of two elements: a Monte Carlo
      generated kernel describing dose deposition in the EPID phosphor, and an
      empirically derived kernel describing optical photon spreading. Relative fluence
      profiles measured with the EPID are in very good agreement with those measured
      with a diamond detector, and exhibit excellent spatial resolution required for
      IMRT verification. For dosimetric verification, the EPID-measured primary
      fluences are convolved with a Monte Carlo kernel describing dose deposition in a
      solid water phantom, and cross-calibrated with ion chamber measurements. Dose
      distributions measured using the EPID agree to within 2.1% with those measured
      with film for open fields of 2 x 2 cm2 and 10 x 10 cm2. Predictions of the EPID
      phantom scattering factors (SPE) based on our scatter kernels are within 1% of
      the SPE measured for open field sizes of up to 16 x 16 cm2. Pretreatment
      verifications of step-and-shoot IMRT treatments using the EPID are in good
      agreement with those performed with film, with a mean percent difference of 0.2
      +/- 1.0% for three IMRT treatments (24 fields).

PMID- 14713080
TI  - Tomosynthesis-based localization of radioactive seeds in prostate brachytherapy.
AB  - Accurately assessing the quality of prostate brachytherapy intraoperatively would
      be valuable for improved clinical outcome by ensuring the delivery of a
      prescribed tumoricidal radiation dose to the entire prostate gland. One necessary
      step towards this goal is the robust and rapid localization of implanted seeds.
      Several methods have been developed to locate seeds from x-ray projection images,
      but they fail to detect completely-overlapping seeds, thus necessitating manual
      intervention. To overcome this limitation, we have developed a new method where
      (1) a three-dimensional volume is reconstructed from x-ray projection images
      using a brachytherapy-specific tomosynthesis reconstruction algorithm with built
      in blur compensation and (2) the seeds are located in this reconstructed volume.
      In contrast to other projection-based methods, our method can detect completely
      overlapping seeds. Our simulation results indicate that we can locate all
      implanted seeds in the prostate using a tomosynthesis angle of 30 degrees and
      seven projection images. The mean localization error is 1.27 mm for a case with
      100 seeds. We have also tested our method using a prostate phantom with 61
      implanted seeds and succeeded in locating all seeds automatically. We believe
      this new method can be useful for the intraoperative quality assessment of
      prostate brachytherapy in the future.

PMID- 14713082
TI  - Influence of scatter reduction method and monochromatic beams on image quality
      and dose in mammography.
AB  - In mammography, the image contrast and dose delivered to the patient are
      determined by the x-ray spectrum and the scatter to primary ratio S/P. Thus the
      quality of the mammographic procedure is highly dependent on the choice of anode
      and filter material and on the method used to reduce the amount of scattered
      radiation reaching the detector. Synchrotron radiation is a useful tool to study
      the effect of beam energy on the optimization of the mammographic process because
      it delivers a high flux of monochromatic photons. Moreover, because the beam is
      naturally flat collimated in one direction, a slot can be used instead of a grid
      for scatter reduction. We have measured the ratio S/P and the transmission
      factors for grids and slots for monoenergetic synchrotron radiation. In this way
      the effect of beam energy and scatter rejection method were separated, and their
      respective importance for image quality and dose analyzed. Our results show that
      conventional mammographic spectra are not far from optimum and that the use of a
      slot instead of a grid has an important effect on the optimization of the
      mammographic process. We propose a simple numerical model to quantify this
      effect.

PMID- 14713083
TI  - Application of the spirometer in respiratory gated radiotherapy.
AB  - The signal from a spirometer is directly correlated with respiratory motion and
      is ideal for target respiratory motion tracking. However, its susceptibility to
      signal drift deters its application in radiotherapy. In this work, a few
      approaches are investigated to control spirometer signal drift for a Bernoulli
      type spirometer. A method is presented for rapid daily calibration of the
      spirometer to obtain a flow sensitivity function. Daily calibration assures
      accurate airflow measurement and also reduces signal drift. Dynamic baseline
      adjustment further controls the signal drift. The accuracy of these techniques
      was studied and it was found that the spirometer is able to provide a long-term
      drift-free breathing signal. The tracking error is comprised of two components:
      calibration error and stochastic signal baseline variation error. The calibration
      error is very small (1% of 3 l) and therefore negligible. The stochastic baseline
      variation error can be as large as 20% of the normal breathing amplitude. In view
      of these uncertainties, the applications of spirometers in treatment techniques
      that rely on breathing monitoring are discussed. Spirometer-based monitoring is
      noted most suitable for deep inspiration breath-hold but less important for free
      breathing gating techniques.

PMID- 14713084
TI  - Determination of the two-dimensional detective quantum efficiency of a computed
      radiography system.
AB  - Based on a recently described method for determining the two-dimensional
      presampling modulation transfer function (MTF), the aperture mask method, a
      method for determining the two-dimensional detective quantum efficiency (DQE) of
      a digital radiographic system was developed. The method was applied to a new
      computed radiography (CR) system and comparisons with one-dimensional
      determinations of the presampling MTF and the DQE were performed. The aperture
      mask method was shown to agree with the conventional tilted slit method for
      determining the presampling MTF along the axes. For the particular CR system
      studied, the mean of one-dimensional determinations of the DQE in orthogonal
      directions led to a representative measure of the average DQE behavior of the
      system up to the Nyquist frequency along the axes, but a deviation was observed
      above this frequency. In conclusion, the method developed for determining the two
      dimensional DQE can be used to determine the imaging properties of a digital
      radiographic detector system over almost the entire frequency domain, the
      exception being the lowest frequencies (< or = 0.1 mm(-1)) at which the validity
      and the reliability of the method are low.

PMID- 14713085
TI  - Deterministic photon transport calculations in general geometry for external beam
      radiation therapy.
AB  - A deterministic method is described for performing three-dimensional (3D) photon
      transport calculations of a LINAC head and phantom/patient geometry to obtain
      dose distributions for therapy planning. The space, energy, and directional
      dependent photon flux density is obtained by numerically solving the Boltzmann
      equation in general 3D geometry using the method of characteristics. The
      deterministic transport calculations use similar ray tracing routines as found in
      Monte Carlo (MC) codes. A special treatment is developed to better represent the
      impact of scattering from accelerator head components. Equations are presented
      for computing the water kerma distribution due to the uncollided and collided
      photon flux density field in the patient region. Kerma results obtained from the
      deterministic computation are compared to Monte Carlo values for a variety of
      source spectra and field sizes. The agreement for kerma values in the beam is
      usually within the MC uncertainties. It is concluded that the deterministic
      method is a rigorous, first-principles approach that could provide a superior
      alternative to Monte Carlo calculations for some types of problems. However
      additional development is needed to provide capability for 3D electron transport
      calculations.

PMID- 14713086
TI  - Validation of target volume and position in respiratory gated CT planning and
      treatment.
AB  - The capability of a commercial respiratory gating system based on video tracking
      of reflective markers to reduce motion-induced CT planning and treatment errors
      was evaluated. Spherical plastic shells (2.8-82 cm3), simulating the gross target
      volume (GTV), were placed in a water-filled body phantom that was moved
      sinusoidally along the longitudinal axis of the CT scanner and the accelerator
      for +/- 1 cm at 15-30 cycle/min. During gated CT imaging, the x-ray exposure was
      initiated by the gating system shortly before the end of expiration (so that the
      imaging time would be centered at the end of expiration); it was terminated by
      the scanner after completion of each slice. In nongated CT images, the target
      appeared distorted and often broken up. GTVs volume errors ranged 16%-110% in
      axial scans, and 7%-36% in spiral scans. In gated CT images, the spheres appeared
      3 and 5 mm longer than their actual diameters (volume errors 2%-16%), at the
      respective respiration rates of 15 and 20 cycles/min. At 30 cycles/min the target
      appeared 1 cm longer, and volume error ranged 25%-53%. During treatment, gating
      kept the beam on for a duration equal to the CT acquisition time of 1 s/slice.
      The difference in positional errors between gated CT and portal films was 1 mm,
      regardless the size of residual motion errors. Because of the potential of
      suboptimal placement of the gating window between CT imaging and treatment, an
      extra 1.5-2.5 mm safety margin can be added regardless of the size of residual
      motion error. For respiratory rates > or = 30 cycles/min, the effectiveness of
      gating is limited by large residual motion in the 1 s CT acquisition time.

PMID- 14713087
TI  - Summary and recommendations of a National Cancer Institute workshop on issues
      limiting the clinical use of Monte Carlo dose calculation algorithms for
      megavoltage external beam radiation therapy.
AB  - Due to the significant interest in Monte Carlo dose calculations for external
      beam megavoltage radiation therapy from both the research and commercial
      communities, a workshop was held in October 2001 to assess the status of this
      computational method with regard to use for clinical treatment planning. The
      Radiation Research Program of the National Cancer Institute, in conjunction with
      the Nuclear Data and Analysis Group at the Oak Ridge National Laboratory,
      gathered a group of experts in clinical radiation therapy treatment planning and
      Monte Carlo dose calculations, and examined issues involved in clinical
      implementation of Monte Carlo dose calculation methods in clinical radiotherapy.
      The workshop examined the current status of Monte Carlo algorithms, the rationale
      for using Monte Carlo, algorithmic concerns, clinical issues, and verification
      methodologies. Based on these discussions, the workshop developed recommendations
      for future NCI-funded research and development efforts. This paper briefly
      summarizes the issues presented at the workshop and the recommendations developed
      by the group.

PMID- 14713088
TI  - An alternative derivation of Katsevich's cone-beam reconstruction formula.
AB  - In this paper an alternative derivation of Katsevich's cone-beam image
      reconstruction algorithm is presented. The starting point is the classical Tuy's
      inversion formula. After (i) using the hidden symmetries of the intermediate
      functions, (ii) handling the redundant data by weighting them, (iii) changing the
      weighted average into an integral over the source trajectory parameter, and (iv)
      imposing an additional constraint on the weighting function, a filtered
      backprojection reconstruction formula from cone beam projections is derived. The
      following features are emphasized in the present paper: First, the nontangential
      condition in Tuy's original data sufficiency conditions has been relaxed. Second,
      a practical regularization scheme to handle the singularity is proposed. Third,
      the derivation in the cone beam case is in the same fashion as that in the fan
      beam case. Our final cone-beam reconstruction formula is the same as the one
      discovered by Katsevich in his most recent paper. However, the data sufficiency
      conditions and the regularization scheme of singularities are different. A
      detailed comparison between these two methods is presented.

PMID- 14713089
TI  - Model of metastatic growth valuable for radionuclide therapy.
AB  - The aim was to make a Monte Carlo simulation approach to estimate the
      distribution of tumor sizes and to study the curative potential of three
      candidate radionuclides for radionuclide therapy: the high-energy electron
      emitter 90Y, the medium-energy electron emitter 177Lu and the low-energy electron
      emitter 103mRh. A patient with hepatocellular carcinoma with recently published
      serial CT data on tumor growth in the liver was used. From these data the growth
      of the primary tumor, and the metastatis formation rate, were estimated. Assuming
      the same tumor growth of the primary and all metastases and the same metastatis
      formation rate from both primary and metastases the metastatic size distribution
      was simulated for various time points. Tumor cure of the metastatic size
      distribution was simulated for uniform activity distribution of three
      radionuclides; the high-energy electron emitter 90Y, the mean-energy electron
      emitter 177Lu and the low-energy electron emitter 103mRh. The simulation of a
      tumor cure was performed for various time points and tumor-to-normal tissue
      activity concentrations, TNC. It was demonstrated that it is important to start
      therapy as early as possible after diagnosis. It was of crucial importance to use
      an optimal radionuclide for therapy. These simulations demonstrated that 90Y was
      not suitable for systemic radionuclide therapy, due to the low absorbed fraction
      of the emitted electrons in small tumors (< 1 mg). If TNC was low 103mRh was
      slightly better than 177Lu. For high TNC values low-energy electron emitters,
      e.g., 103mRh was the best choice for tumor cure. However, the short half-life of
      103mRh (56 min) might not be optimal for therapy. Therefore, other low-energy
      electron emitters, or alpha emitters, should be considered for systemic targeted
      therapy.

PMID- 14713090
TI  - Feldkamp-based cone-beam reconstruction for gantry-tilted helical multislice CT.
AB  - Depending on the clinical application, it is frequently necessary to tilt the
      gantry of an x-ray CT system with respect to the patient and couch. For single
      slice fan-beam systems, tilting the gantry introduces no errors or artifacts.
      Most current systems, however, are helical multislice systems with up to 16
      slices. The multislice helical reconstruction algorithms used to create CT images
      must be modified to account for tilting of the gantry. If they are not, the
      quality of reconstructed images will be poor with the presence of significant
      artifacts, such as smearing and double-imaging of anatomical structures. Current
      CT systems employ three primary types of reconstruction algorithms: helical fan
      beam approximation, advanced single-slice rebinning, and Feldkamp-based
      algorithms. This paper presents a generalized helical cone-beam Feldkamp-based
      algorithm that is valid for both tilted and nontilted orientations of the gantry.
      Unlike some of the other algorithms, generalization of the Feldkamp algorithm to
      include gantry tilt is simple and straightforward with no significant increase in
      computational complexity. The effect of gantry tilt for helical Feldkamp
      reconstruction is to introduce a lateral shift in the isocenter of the
      reconstructed slice of interest, which is a function of the tilt, couch speed,
      and view angle. The lateral shift is easily calculated and incorporated into the
      helical Feldkamp backprojection algorithm. A tilt-generalized helical Feldkamp
      algorithm has been developed and incorporated into Aquilion 16-slice CT (Toshiba,
      Japan) scanners. This paper describes modifications necessary for the tilt
      generalization and its verification.

PMID- 14713091
TI  - Monte Carlo simulation of the image formation process in portal imaging.
AB  - We have written Monte Carlo programs to simulate the formation of radiological
      images. Our code is used to propagate a simulated x-ray fluence through each
      component of an existing video-based portal imaging system. This simulated
      fluence consists of a 512 x 512 pixel image containing both contrast-detail
      patterns as well as checker patterns to assess spatial resolution of the
      simulated portal imager. All of the components of the portal imaging system were
      modeled as a cascade of eight linear stages. Using this code, one can assess the
      visual impact of changing components in the imaging chain by changing the
      appropriate probability density function. Virtual experiments were performed to
      assess the visual impact of replacing the lens and TV camera by an amorphous
      silicon array, and the effect of scattered radiation on portal images.

PMID- 14713092
TI  - Carotid geometry reconstruction: a comparison between MRI and ultrasound.
AB  - Image-based Computational Fluid Dynamics (CFD) has become a popular tool for the
      prediction of in vivo flow profiles and hemodynamic wall parameters. Currently,
      Magnetic Resonance Imaging (MRI) is most widely used for in vivo geometry
      acquisition. For superficial arteries such as the carotids and the femoral
      artery, three-dimensional (3-D) extravascular ultrasound (3-DUS) could be a cost
      effective alternative to MRI. In this study, nine healthy subjects were scanned
      both with MRI and 3-DUS. The reconstructed carotid artery geometries for each
      subject were compared by evaluating cross-sectional areas, centerlines, and
      carotid nonplanarity. Lumen areas agreed very well between the two different
      acquisition techniques, whereas centerlines and nonplanarity parameters showed
      measurable disagreement, possibly due to the different neck and head positions
      adopted for 3-DUS versus MRI. With the current level of agreement achieved, 3-DUS
      has the potential to become an inexpensive and fast alternative to MRI for image
      based CFD modeling of superficial arteries.

PMID- 14713093
TI  - Changing the culture of blame.

PMID- 14713094
TI  - Periventricular leukomalacia: pathophysiologic concerns due to immature
      development of the brain.

PMID- 14713095
TI  - A deadly prion disease: fatal familial insomnia.
AB  - Fatal familial insomnia (FFI) is an inherited disease caused by a mutation in the
      protein prion gene. Symptoms of FFI closely resemble those of familial
      Creutzfeldt-Jakob disease, making genetic testing and histological examination of
      brain tissue the only means to determine a definitive diagnosis. The disease is
      rare--approximately 60 cases have been detected worldwide since 1986. Incubation
      time of the disease may be as long as 30 years; death generally occurs within 1
      year of the onset of symptoms. There is no known procedure or treatment for
      delaying the onset of symptoms or modifying the disease course. Nurses who
      confront patients with FFI will be challenged to provide care to a patient and
      family who are facing certain death.

PMID- 14713096
TI  - The psychosocial impact of late-stage Parkinson's disease.
AB  - The late stage of Parkinson's disease (PD) can be protracted with inexorable
      changes in physical and mental health, loss of autonomy and self-esteem, altered
      relationships, and social isolation. Severely affected patients (Hoehn & Yahr
      stage 4-5) present a challenge to nurses who care for them; addressing their
      needs takes time and patience. Changes in mental status have profound
      implications for the welfare of the late-stage PD patient as well as of the
      caregiver(s). Depression and dementia in patients with PD are two factors that
      interfere with the ability to deliver effective care in late-stage PD as they
      lead to loss of initiative and cooperation. Primary caregivers often have their
      own medical problems, with limited stamina and support; relationships may change,
      leading to sadness or conflict. Nurses can be powerful advocates for the physical
      and mental health of both the patient with late-stage Parkinson's disease and the
      primary caregiver.

PMID- 14713097
TI  - Cognitive symptoms and correlates of physical disability in individuals with
      multiple sclerosis.
AB  - There are inconsistencies in the literature regarding the prevalence of cognitive
      impairment among individuals with multiple sclerosis (MS). The purpose of this
      study was to examine perceived cognitive impairment in secondary progressive and
      relapsing-remitting multiple sclerosis (MS) and to examine the relationship
      between level of disability, age, and number of years with MS and self-reported
      cognitive symptoms. The sample consisted of 447 individuals (96 participants with
      secondary progressive MS and 351 participants with MS) who responded to mailed
      data collection instruments. The Performance Scales, a self-report measure of
      disability in eight domains of function, and a sociodemographic data sheet were
      analyzedfor this study. Of individuals with secondary progressive MS, 83%
      reported cognitive symptoms, while 82% of individuals with relapsing-remitting MS
      reported cognitive symptoms. Individuals with secondary progressive MS were
      reportedly experiencing a significantly greater level of total disability. A
      statistically significant, strong, positive relationship was found between
      cognitive symptoms and fatigue for those with secondary progressive MS and those
      with relapsing-remitting MS. Statistically significant, moderate, positive
      relationships were also found between cognitive symptoms in those with secondary
      progressive MS and those with relapsing-remitting MS, and sensory symptoms,
      vision, hand function, bladder/bowel symptoms, and spasticity. A statistically
      significant, weak, positive relationship was found between cognitive symptoms and
      mobility in individuals with relapsing-remitting MS. There was no relationship
      between cognitive symptoms and mobility in those with secondary progressive MS.
      Cognitive symptoms were not significantly related to age in those with secondary
      progressive MS or those with relapsing-remitting MS. In addition, cognitive
      symptoms were not significantly related to the number of years with MS in
      individuals with secondary progressive MS or those with relapsing-remitting MS.
      The perception of cognitive deficits in individuals with MS was found in this
      study to be even more prevalent than previously reported. Because cognitive
      deficits occur at all stages of MS, early identification and treatment is
      essential. Healthcare providers must aggressively screen for cognitive impairment
      and rehabilitate individuals with MS who exhibit symptoms.

PMID- 14713098
TI  - Pharmacologic management of cancer pain.
AB  - Chronic malignant pain is experienced by as many as 80% of patients with cancer.
      While these patients may experience either nociceptive or neuropathic pain,
      oftentimes a mixed presentation is encountered. Nociceptive pain may respond to
      opioid and nonopioid analgesics, while antidepressants and antiepileptics may be
      beneficial for neurogenic pain. New evidence points to efficacy of opioids for
      neuropathic, in addition to nociceptive pain syndromes, further clarifying the
      use of these agents for this patient population. When used properly, opioids are
      a safe and effective tool for the management of cancer pain.

PMID- 14713099
TI  - The fundamentals of variant Creutzfeldt-Jakob disease.
AB  - Since the discovery of a variant form of Creutzfeldt-Jakob disease (vCJD), the
      human form of bovine spongiform encephalopathy, researchers have been persistent
      in their search for the way in which this disease manifests itself in humans.
      Like all other forms of CJD, vCJD is a prion disease, or transmissible spongiform
      encephalopathy. The differences from other forms of CID are its manifestation and
      the population at risk. Diagnosing the disease remains a problem because true
      diagnosis can be determined only by postmortem evaluation. Because there is no
      treatment for vCJD or any form of CJD, palliative care is the foundation of care.
      Nurses should know the risks of the disease and understand its pathogenesis not
      only to explain modes of transmission to families but also to be able to protect
      themselves. Researchers are currently investigating a genetic link as well as the
      immunological relationship of this disease in hopes of providing more answers
      related to transmissibility, incubation, and risk for the disease.

PMID- 14713100
TI  - The pharmacologic treatment of vasospasm after subarachnoid hemorrhage: a case
      study.
AB  - The patient with a diagnosis of SAH and subsequent vasospasm presents many
      nursing challenges and requires complex pharmacologic management. By paying
      careful attention to the therapeutic and potential side effects of the
      medications prescribed, the nurse can be instrumental in the patient's recovery.

PMID- 14713101
TI  - Bispectral Index monitoring in the neurointensive care unit.
AB  - Although the BIS monitor is relatively new to the intensive care setting, it can
      be a very beneficial tool in monitoring neurological patients. Having minute-to
      minute indicators and reassurance of adequate sedation in the neuromuscular
      blockaded patient enables neuroscience nurses to provide better care. More timely
      and current measurements of pentobarbital serum levels can help reduce and
      prevent life-threatening complications in this patient population. Much research
      has been done on its use, and further research is needed into the monitor's many
      uses.

PMID- 14713102
TI  - Comparative studies on the secretion and activation of MMPs in two reconstructed
      human skin models using HaCaT- and HaCaT-ras-transfected cell lines.
AB  - Matrix metalloproteinases play an important role in tissue regeneration, wound
      healing and tumor invasion. Our previous studies have shown a higher motility of
      HaCaT-ras-transfected cells compared with HaCaT or normal human keratinocytes
      (NHK) in correlation with a higher secretion of MMP-2 (72 kDa) or MMP-9 (92 kDa),
      according to the medium used for cell cultures. Presently, the expression and
      activity of MMPs were investigated in two reconstructed skin models, using a dead
      de-epidermized dermis (DED) or a dermal substitute including living fibroblasts.
      In all experiments, MMP-9 was essentially secreted by NHK and to a greater extent
      by HaCaT cells. Its active form (86 kDa) was only detected in both reconstructed
      skin models according to keratinocyte differentiation. MMP-2 was mainly secreted
      by living fibroblasts included in the dermal substitute skin model. In this case,
      its activation was up-regulated when HaCaT cell lines were seeded onto the dermal
      substitute according to their culture at air/liquid interface as shown for MMP-9.
      The collagenase MMP-1 and stromelysin-1 (MMP-3), susceptible to activate pro-MMP
      2 and -9, respectively, were detected in their inactive form by ELISA. MMP-1 was
      expressed in both models but MMP-3 required the presence of living fibroblasts.
      Their activities were not detected using specific fluorogenic substrates. In the
      skin equivalent model using HaCaT, the extensive secretion and activation of MMP
      2 and MMP-9 could explain the defect observed in basal membrane reconstruction,
      suggesting a direct interaction of HaCaT with fibroblasts.

PMID- 14713103
TI  - Melanoma invasion in reconstructed human skin is influenced by skin cells-
      investigation of the role of proteolytic enzymes.
AB  - Melanoma invasion is a complex multi stage process involving changes to the
      cell/extracellular matrix (ECM) and cell/cell interactions. We have previously
      shown using an in vitro model of reconstructed human skin (consisting of human
      dermis with a basement membrane [BM] and populated with human skin cells) that
      some melanoma cells (HBL cell line) invade more actively in the presence of
      adjacent normal skin cells. The aim of the present study was to further
      investigate the relationship between melanoma cells, skin cells and ECM proteins
      during melanoma cell invasion through reconstructed skin, extending this to a
      study of three melanoma cell lines. We also examined whether such cell/cell
      induced invasion is due to increased expression and activation of matrix
      metalloproteinase-2 (MMP-2) and MMP-9, or due to increases in general protease
      activity for keratinocytes, fibroblasts or melanoma lines. Addition of skin cells
      dramatically altered the invasive behaviour of the three metastatic melanoma cell
      lines (HBL, C8161 and A375SM) used; they increased the invasive ability of HBLs
      which were unable to invade on their own; they potentiated the invasion of C8161
      cells which were invasive in their own right, but reduced the invasion of A375-SM
      cells which were aggressive invaders in the absence of skin cells. Latent forms
      of MMP-2, and MMP-9, were clearly expressed by the normal skin cells whereas all
      three melanoma lines weakly expressed these proteases. Fibroblast and
      keratinocyte MMPs were activated specifically by culture on type I collagen and
      on dermis which retained an intact basement membrane. These findings demonstrate
      that while there is an active communication between melanoma cells and adjacent
      skin cells, the invasive process is dictated by the melanoma cells and not the
      skin cells. However, activation of skin cell derived MMPs may play an important
      role in facilitating invasion by particular melanoma phenotypes.

PMID- 14713104
TI  - S100A4 regulates membrane induced activation of matrix metalloproteinase-2 in
      osteosarcoma cells.
AB  - To study the role of the metastasis associated protein S100A4, an osteosarcoma
      cell line (OHS) with a high level of this protein was transfected with a vector
      containing a ribozyme that degrades S100A4 mRNA and, as controls, OHS cells were
      transfected with the vector alone. We have followed up our previous investigation
      (Bjornland et al. 1999) by a detailed investigation of these cell lines'
      synthesis of MMP and TIMP proteins at different cell densities. It is shown that
      the cell lines with a low S100A4 level produced a reduced amount of
      immunoreactive MMP-2 at cellular subconfluence, while at confluence there was no
      difference compared to the control cells. The cell lines with a reduced S100A4
      level produced less of the activated form of MMP-2 (62-kDa) and less TIMP-1 than
      the corresponding control cells, independent of cell density. Isolated cell
      membranes from cell lines with a reduced S100A4 level contained less MT1-MMP, MMP
      2 and TIMP-2 compared to the control cells. Activation of exogenously added
      proMMP-2 was less effective with the former membrane preparations. It appeared
      that the mechanism behind the S100A4 dependent activation of proMMP-2 varied with
      cell density, as SN50, a peptide inhibitor of NF-kappaB nuclear translocation
      reduced the activation of MMP-2 at low cell density, but had no effect at high
      cell density. Thus, one of the mechanisms by which S100A4 may exert its effect on
      metastasis of some tumors is by regulating the MMP-2 activity.

PMID- 14713105
TI  - Rat colon carcinoma cells that survived systemic immune surveillance are less
      sensitive to NK-cell mediated apoptosis.
AB  - In order to form distant metastases, cells from the primary tumor have to detach,
      enter the blood- or lymph-compartment and escape immune surveillance. Here, we
      describe the selection of rat colon carcinoma cell lines (CC531s-m1 and CC531s
      m2) that escaped from systemic immune surveillance; CC531s cells were injected
      into the v. jugularis of Wag/Rij rats, after three weeks the lung tumors were
      isolated, the tumor cells were cultured, characterized and injected again. The m1
      and m2-cell lines were less susceptible for killing by syngeneic NK cells.
      Further characterization of this cell line showed a decreased sensitivity towards
      TRAIL- and CD95L-, but not to granzyme B-mediated apoptosis. In the m1- and m2
      cells log-phase growth started earlier as compared to the parental cell line,
      whereas no changes were found in anchorage-dependent or anchorage-independent
      growth. After subcapsular injection of the m2-cell line into the liver of rats
      much more lung metastases were formed in comparison to injection of the parental
      cell line. In conclusion, the results suggest that the resistance of the m1- and
      m2-cells to NK cell-mediated apoptosis was associated with their capability to
      survive systemic immune surveillance and form metastases in vivo.

PMID- 14713106
TI  - Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different
      metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation
      of metastatic phenotype.
AB  - In the present study, we examined the autocrine/paracrine role of IL-8 in
      melanoma growth and metastasis by analyzing the expression and functional
      significance of IL-8 receptors, CXCR1 and CXCR2 in human malignant melanoma cells
      with different metastatic potential. CXCR1 and CXCR2 mRNA and protein levels were
      analyzed by reverse trannscriptase-based polymerase chain reaction,
      immunohistochemistry, immunoprecipitation, flow cytometry and ligand binding
      assay in melanoma cells in vitro and xenografted in nude mice. Melanoma cells
      constitutively expressed CXCR1 and CXCR2 mRNA and protein. Highly metastatic
      A375SM cells expressed higher levels of CXCR1 and CXCR2 mRNA and protein in vitro
      and in vivo as compared to low metastatic A375P and non-metastatic SBC-2 melanoma
      cells. Treatment of SBC-2 and A375P cells with exogenously added recombinant IL-8
      significantly enhanced their proliferation and invasive potential. Further
      neutralizing antibodies to CXCR1 and CXCR2 inhibited proliferation and invasive
      potential of unstimulated and IL-8-stimulated A375P cells. In summary, the data
      suggest that constitutive expression of CXCR1 and CXCR2 play an important role
      regulating the IL-8-mediated metastatic phenotype in human malignant melanoma
      cells.

PMID- 14713107
TI  - Bioluminescent imaging (BLI) to improve and refine traditional murine models of
      tumor growth and metastasis.
AB  - Bioluminescent imaging (BLI) permits sensitive in vivo detection and
      quantification of cells specifically engineered to emit visible light. Three
      stable human tumor cell lines engineered to express luciferase were assessed for
      their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis
      models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted
      subcutaneously into SCID-beige mice and were monitored for tumor growth and
      response to 5-FU and mitomycin C treatments. Progressive tumor development and
      inhibition/regression following drug treatment were observed and quantified in
      vivo using BLI. Imaging data correlated to standard external caliper measurements
      of tumor volume, but bioluminescent data permitted earlier detection of tumor
      growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung
      cancer cells were injected intravenously and lung metastases were monitored in
      vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a
      temporal assessment of in vivo lung tumor growth. This longitudinal study design
      permitted an accurate, real-time evaluation of tumor burden in the same animals
      over time. End-point bioluminescence measured in vivo correlated to total lung
      weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT
      29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases
      to lung and lymph nodes in SCID-beige mice. Both primary tumors and
      micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung
      lobes and lymph nodes confirmed the in vivo signals and indicated a slightly
      higher frequency of metastasis in some mice. Levels of bioluminescence from in
      vivo and ex vivo images corresponded to the frequency and size of metastatic
      lesions in lungs and lymph nodes as subsequently confirmed by histology. In
      summary, BLI provided rapid, non-invasive monitoring of tumor growth and
      regression in animals. Its application to traditional oncology animal models
      offers quantitative and sensitive analysis of tumor growth and metastasis. The
      ability to temporally assess tumor development and responses to drug therapies in
      vivo also improves upon current standard animal models that are based on single
      end point data.

PMID- 14713108
TI  - In vivo monitoring of tumor relapse and metastasis using bioluminescent PC-3M-luc
      C6 cells in murine models of human prostate cancer.
AB  - We used the bioluminescent human prostate carcinoma cell line PC-3M-luc-C6 to non
      invasively monitor in vivo growth and response of tumors and metastasis before,
      during and after treatments. Our goal was to determine the utility of a
      luciferase-based prostate cancer animal model to specifically assess tumor and
      metastatic recurrence in vivo following chemotherapy. Bioluminescent PC-3M-luc-C6
      cells, constitutively expressing luciferase, were implanted into the prostate or
      under the skin of mice for primary tumor assessment. Cells were also injected
      into the left ventricle of the heart as an experimental metastasis model. Weekly
      serial in vivo images were taken of anesthetized mice that were untreated or
      treated with 5-fluorouracil or mitomycin C. Ex vivo imaging and/or histology was
      used to confirm and localize metastatic lesions in various tissues initially
      detected by images in vivo. Our in vivo data detected and quantified early
      inhibition of subcutaneous and orthotopic prostate tumors in mice as well as
      significant tumor regrowth post-treatment. Local and distal metastasis was
      observed within seven days following intracardiac injection of PC-3M-luc-C6
      cells. Differential drug responses and metastatic tumor relapse patterns were
      distinguished over time by in vivo imaging depending on the metastatic site. The
      longitudinal evaluation of bioluminescent tumor and metastatic development within
      the same cohorts of animals permitted sensitive and quantitative assessment of
      both primary and metastatic prostate tumor response and recurrence in vivo.

PMID- 14713109
TI  - SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental
      breast cancer bone metastasis model.
AB  - The aim of the study was to investigate inhibitory effects of the receptor
      tyrosine kinase (RTK) inhibitor SU11248 against CSF-1R and osteoclast (OC)
      formation. We developed an in vivo model of breast cancer metastasis to evaluate
      efficacy of SU11248 against tumor growth and tumor-induced osteolysis in bone.
      The in vitro effects of SU11248 on CSF-1R phosphorylation, OC formation and
      function were evaluated. Effects on 435/HAL-Luc tumor growth in bone were
      monitored by in vivo bioluminescence imaging (BLI), and inhibition of osteolysis
      was evaluated by measurement of serum pyridinoline (PYD) concentration and
      histology. Phosphorylation of the receptor for M-CSF (CSF-1R) expressed by NIH3T3
      cells was inhibited by SU11248 with an IC50 of 50-100 nM, consistent with CSF-1R
      belonging to the class III split kinase domain RTK family. The early M-CSF
      dependent phase of in vitro murine OC development and function were inhibited by
      SU11248 at 10-100 nM. In vivo inhibition of osteolysis was confirmed by
      significant lowering of serum PYD levels following SU11248 treatment of tumor
      bearing mice (P = 0.047). Using BLI, SU11248 treatment at 40 mg/kg/day for 21
      days showed 64% inhibition of tumor growth in bone (P = 0.006), and at 80
      mg/kg/day showed 89% inhibition (P = 0.001). Collectively, these data suggest
      that SU11248 may be an effective and tolerated therapy to inhibit growth of
      breast cancer bone metastases, with the additional advantage of inhibiting tumor
      associated osteolysis.

PMID- 14713110
TI  - A tribute to John Wendell Severinghaus.

PMID- 14713111
TI  - Fire-air and dephlogistication. Revisionisms of oxygen's discovery.
AB  - Americans are taught that Joseph Priestley discovered oxygen in 1774 and promptly
      brought that news to Lavoisier. Lavoisier proved that air contained a new
      element, oxygen, which combined with hydrogen to make water. He disproved the
      phlogiston theory but Priestley called it dephlogisticated air until his death 30
      years later. Scandanavians learn that a Swedish apothecary Carl Wilhelm Scheele
      beat Priestley by 2 years but was deprived of credit because Lavoisier denied
      receiving a letter Scheele later claimed to have sent in September 1774
      describing his 1772 discovery of "fire air". His claim was unconfirmed because
      Scheele first published his work in 1777. However, Scheele's missing letter was
      made public in 1992 in Paris, 218 years late, and now resides at the French
      Academie de Sciences. Lavoisier received it on Oct 15, 1774. His guilt was kept
      secret in the effects of Madame Lavoisier. He failed on several occasions to
      credit either Priestley or Scheele for contributing to the most important
      discovery in the history of science. Priestley was a teacher, political
      philosopher, essayist, Unitarian minister and pioneer in chemical and electrical
      science. He discovered 9 gases including nitrous oxide. He invented soda water,
      refrigeration, and gum erasers for which he coined the term "rubber". He
      discovered photosynthesis. He was humorless, argumentative, brilliant and
      passionate, called a "furious free-thinker". While his liberal colleagues Josiah
      Wedgwood, Erasmus Darwin, James Watts, and others of the Lunar Society were
      celebrating the 2nd anniversary of the French revolution, a Birmingham mob,
      supported by the royalists and the established church, destroyed Priestley's
      home, laboratory and church. Driven from England, he emigrated to Pennsylvania
      where he built a home and laboratory and collected a 1600 volume library, then
      among the largest in America. He is regarded as a founder of liberal Unitarian
      thinking. He was friend and correspondent of Thomas Jefferson. His philosophy and
      insight persuaded Jefferson to initiate what Americans call a liberal arts
      education. Scheele was later recognized as a brilliant and productive pioneer in
      chemistry although he died at age 44 of tasting his own arsenic compounds. In the
      new time-lapse play "Oxygen" set in Stockholm in both 18th and 21st centuries, in
      1774, blame falls on Lavoisier's wife who hid Scheele's letter in hopes of giving
      her husband sole credit for discovering oxygen. In 2001, four Nobel committee
      panelists cannot agree which should receive the first "Retro-Nobel Prize" for the
      greatest discovery of all time: Priestley, Scheele or Lavoisier or all three. The
      audience is asked to choose.

PMID- 14713112
TI  - Mammalian hibernation. Transcriptional and translational controls.
AB  - Mammalian hibernation is an amazing strategy for winter survival. Animals sink
      into a deep torpor where metabolic rate is < 5% of normal, body temperature falls
      to 0-5 degrees C, and physiological functions are strongly suppressed.
      Hibernation is a closely regulated process that includes multiple controls on
      gene transcription and protein translation, the primary subjects of this review.
      Recent studies by our lab and others have used multiple techniques of gene
      discovery, including cDNA array screening, to identify genes that are up
      regulated in hibernation and continuing studies are tracing the functions of the
      encoded proteins and the signal transduction systems that regulate expression.
      For example, up-regulation of fatty acid binding proteins during hibernation
      facilitates the switch to a primary dependence on lipid fuels by nearly all
      organs and new studies have shown that up-regulation is mediated by the PPARgamma
      transcription factor and its co-activator, PGC-1. Several hypoxia-related genes
      including HIF-1alpha are also up-regulated during hibernation suggesting a role
      for this transcription factor in mediating adaptive responses for hibernation.
      Controls on mRNA translation during hibernation accomplish two goals: a general
      strong suppression of protein synthesis that contributes to energy savings and
      the selected synthesis of a few specific proteins. These goals are accomplished
      by mechanisms that include reversible phosphorylation controls on ribosomal
      initiation and elongation factors and differential distribution of individual
      mRNA species between polysome and monosome fractions. Studies of gene expression,
      protein synthesis regulation, controls on fuel metabolism, and signal
      transduction pathways are combining to produce an integrated model of the
      biochemical regulation of hibernation.

PMID- 14713113
TI  - Oxygen conformance of cellular respiration. A perspective of mitochondrial
      physiology.
AB  - Oxygen pressure declines from normoxic air-level to the microenvironment of
      mitochondria where cytochrome c oxidase (COX) reduces oxygen to water at oxygen
      levels as low as 0.3 kPa (2 Torr; 3 microM; 1.5 % air saturation). Intracellular
      hypoxia is defined as (1) local oxygen pressure below normoxic reference states,
      or (2) limitation of mitochondrial respiration by oxygen levels below kinetic
      saturation, resulting in oxyconformance. High-resolution respirometry provides
      the methodology to measure mitochondrial and cellular oxygen kinetics in the
      relevant low oxygen range < 1 kPa (7.5 mmHg; 9-10 microM; 5% air saturation).
      Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics
      with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 microM) in
      ADP-stimulated state 3. Thus mitochondrial respiration proceeds at 90% of its
      hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small
      but significant oxygen limitation even under normoxia in active muscle. Any
      impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a
      shift of mitochondrial oxygen kinetics to the right, particularly by competitive
      inhibition of COX by NO, causes a further depression of respiration and a
      compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen
      uptake increases above hyperbolic saturation, which is probably due to oxygen
      radical production rather than the kinetics of COX. In cultured cells, the
      pronounced oxygen uptake above mitochondrial saturation at air-level oxygen
      pressure cannot be inhibited by rotenone and antimycin A, amounting to > 20 % of
      routine respiration in fibroblasts. Biochemical models of oxyconformance of COX
      are evaluated relative to patterns of intracellular oxygen distribution in the
      tissue and enzyme turnover in vivo, considering the kinetic effects of COX excess
      capacity on flux through the mitochondrial electron transport chain.

PMID- 14713114
TI  - Current paradigms in cellular oxygen sensing.
AB  - Organisms, tissues and cells react to hypoxia by activating adaptive responses
      that tend to preserve systemic oxygen transport, cellular oxygen delivery, and
      the resistance of cells against the consequences of severe hypoxia. These
      responses are required for embryonic development and for survival through
      adulthood. Although much has been learned about the signaling pathways that are
      activated in hypoxic cells, the underlying mechanism of O2 sensing is not
      established. Most of the putative models of O2 sensing include the involvement of
      redox-dependent reactions and many implicate reactive oxygen species in the
      signaling process. The sources of these oxidant signals are thought to include
      members of the NAD(P)H oxidase system and/or mitochondria. This article reviews
      evidence for and against the involvement of these systems in the O2 sensing
      pathway.

PMID- 14713115
TI  - Why is erythropoietin made in the kidney? The kidney functions as a 'critmeter'
      to regulate the hematocrit.
AB  - The normal hematocrit is not a random number, but one that maximizes oxygen
      delivery. While the feedback loop wherein tissue oxygen pressure determines the
      production of erythropoietin, which further drives the production of red blood
      cells in the bone marrow, explains how the hematocrit is generated, it does not
      speak to how the hematocrit is regulated. The regulation of the hematocrit
      requires the coordination of the plasma volume and the red cell mass. By
      controlling red cell mass via erythropoietin and plasma volume through excretion
      of salt and water, the kidney is able to generate the hematocrit. It is
      hypothesized that the kidney functions as a critmeter by sensing the relative
      volumes of each component of the blood through the common signal of tissue oxygen
      tension. The kidney's unique ability to sense ECF volume through tissue oxygen
      signal allows it to coordinate these two volumes to produce the normal
      hematocrit. Hence, it may be the kidneys ability to report a measure of ECF
      volume as a tissue oxygen signal and thus to regulate the hematocrit that
      establishes it as the logical site of erythropoietin production. The critmeter is
      proposed to be a functional unit located at the tip of the cortical labyrinth at
      the juxta-medullary region of the kidney where erythropoietin is made
      physiologically. Renal vasculature and nephron segment heterogeneity in sodium
      reabsorption likely provides the anatomical construct to generate the marginal
      tissue oxygen pressure required to trigger the production of erythropoietin. The
      balance of oxygen consumption for sodium reabsorption and oxygen delivery is
      reflected by the tissue oxygen pressure. This balance hence determines RBC mass
      adjusted to plasma volume. Factors that affect blood supply and sodium
      reabsorption in a discordant manner may modulate the critmeter, e.g. angiotensin
      II. The objective of this work is to describe the hypothesis of the kidney's
      function as a critmeter, including the anatomical and physiological components,
      and the role of the renin-angiotensin system in modulating erythropoietin.
      Clinical examples of the dysregulation of the critmeter may be found in the
      anemia of renal failure and in sports anemia.

PMID- 14713116
TI  - Hypoxia and high altitude. The molecular response.
AB  - Increased erythropoietin plasma levels and the consequent augmented production of
      red blood cells is the best known systemic adaptation to reduced oxygen partial
      pressure (pO2). Intensive research during the last years revealed that the
      molecular mechanism behind the regulation of erythropoietin is ubiquitous and has
      far more implications than first thought. Erythropoietin regulation results from
      the activation of the hypoxia-inducible factor-1 (HIF-1) pathway under hypoxic
      conditions. HIF-1 is a heterodimer consisting of an oxygen sensitive--HIF-1--and
      an oxygen-independent subunit--HIF-1beta (also known as the aryl hydrocarbon
      receptor nuclear translocator--ARNT). In addition to erythropoietin, more than 30
      genes are now known to be up-regulated by HIF-1. Recently, the critical
      involvement of HIF-1alpha post-translational modifications in the cellular oxygen
      sensing mechanism was discovered. In this review we will focus on the regulation
      of the HIF-1 pathway and the cellular oxygen sensor and discuss their
      implications in high altitude hypoxia.

PMID- 14713117
TI  - Hypoxia and lung branching morphogenesis.
AB  - Morphogens, growth factors and extracellular matrix (ECM) components modulate
      early lung branching, and have been studied extensively both in vivo and in
      vitro. In vitro studies have been particularly useful, because tissue can be
      manipulated either chemically or mechanically. For the most part, such studies
      have been conducted at ambient oxygen tensions, despite the fact that the fetus
      develops in a low oxygen environment. Since oxygen tension regulates the
      expression of various growth factors, adhesion molecules and their receptors, we
      investigated whether the low oxygen environment of the fetus contributes towards
      lung branching morphogenesis by affecting one or more these mediators. Using an
      established fetal lung explant model, we demonstrated that in comparison to
      tissues cultured at ambient oxygen concentration (21% O2), fetal lung explants
      cultured at 3% O2 show increases in terminal branching and cellular
      proliferation, and they display appropriate proximal to distal differentiation.
      To investigate the factor(s) mediating the induction of lung branching
      morphogenesis and differentiation by fetal oxygen tension, we focused on matrix
      metalloproteinases (MMPs), a group of zinc-dependent enzymes that modify ECM
      structure and function. Our results reveal that hypoxia suppresses MMP activity,
      leading to the accumulation of specific ECM components, including tenascin-C (TN
      C), that act to stimulate lung branching. These studies demonstrate that low
      oxygen in the setting of the developing lung positively regulates lung branching
      morphogenesis, and suggest that the pathologic responses to low oxygen in the
      adult lung reflect a dysregulation of this lung developmental program.

PMID- 14713118
TI  - Hypoxia and Rho/Rho-kinase signaling. Lung development versus hypoxic pulmonary
      hypertension.
AB  - Intracellular signaling via the small GTP-binding protein RhoA and its downstream
      effector Rho-kinase plays a role in regulating diverse cellular functions,
      including cell contraction, migration, gene expression, proliferation, and
      differentiation. Rho/Rho-kinase signaling has an obligatory role in embryonic
      cardiac development, and low-level chemical activation of Rho promotes branching
      morphogenesis in fetal lung explants. Gebb has found that hypoxia markedly
      augments branching morphogenesis in fetal rat lung explants, and our preliminary
      results suggest this is associated with activation of RhoA. Whereas hypoxia
      induced activation of Rho/Rho-kinase may promote fetal lung development, other
      evidence indicates it has adverse effects in the lungs of neonates and adults.
      When exposed at birth to the mild hypoxia of Denver's altitude (5,280 ft), the
      neonatal fawn-hooded rat (FHR) develops severe pulmonary hypertension (PH)
      associated with impaired lung alveolarization and vascularization. We have
      observed that administration via the drinking water of the Rho-kinase inhibitor
      fasudil to the nursing, Denver FHR mother for the first 2 to 3 weeks, and then
      directly to the Denver FHR pups for the next 7 to 8 weeks, ameliorates the lung
      dysplasia and PH. The adult Sprague-Dawley rat develops PH when exposed for 3 to
      4 wk to a simulated altitude of 17,000 ft. We have found that this hypoxic PH is
      associated with activation of pulmonary artery Rho/Rho-kinase and is almost
      completely reversed by acute intravenous administration of the Rho-kinase
      inhibitor Y-27632. In addition, chronic in vivo treatment with Y-27632 reduces
      development of the hypoxic PH. In summary, hypoxic activation of Rho/Rho-kinase
      signaling may be important for fetal lung morphogenesis, but continued activation
      of this pathway in the neonate impairs postnatal lung development and re
      activation in the adult contributes to development of PH.

PMID- 14713119
TI  - Hypoxic induction of myocardial vascularization during development.
AB  - The development of the heart is closely linked to its temporally and spatially
      regulated vascularization. Hypoxia has been shown to stimulate myocardial
      capillary growth and improve myocardial perfusion during reperfusion in postnatal
      animals exposed to chronic or intermittent exposure to hypobaria. Vascular
      endothelial growth factor (VEGF) is up-regulated by hypoxia via HIF-1alpha, and
      these two molecules are colocalized with presumptive regions of hypoxia. VEGF up
      regulation in embryonic and fetal hearts correlates with vascular tube formation
      which progresses from an epicardial to endocardial direction prior to the
      establishment of a functional coronary circulation. Our studies on explanted
      embryonic quail hearts indicate that vascular tube formation is enhanced by
      hypoxia (5-10% O2) and inhibited by hyperoxia. Three splice variants of VEGF
      (122, 126, 190) were found to increase and decrease with hypoxia and hyperoxia,
      respectively. While VEGF synthesis is stimulated by hypoxia, there are
      differences in the vascular patterning between exogenous VEGF-induced
      vascularization and that induced by hypoxia. Thus, other, yet to be identified,
      molecules are recruited by hypoxia. Acute hypoxia selectively enhances at least
      three splice variants of VEGF-A, and also selectively up-regulates VEGFR-1 (flt
      1). However, we suggest that VEGF-B, a ligand for VEGFR-1 may contribute to
      embryonic myocardial vascularization, since we have shown that it plays a key
      role in this process under normoxic conditions. A second mechanism by which
      hypoxia may play a role in vascularization of the heart is via its vasodilatory
      effects, once the coronary circulation is functional. Increased blood flow serves
      as a mechanical (stretch) trigger for activation of VEGF and its receptors. In
      sum, there is evidence that a relative hypoxia provides both metabolic and
      mechanical stimuli for vascular growth in the developing heart.

PMID- 14713120
TI  - Role of cerebral blood volume in acute mountain sickness.
AB  - This review focuses on the role of cerebral blood volume in the intracranial
      hemodynamics that may influence the pathophysiology of acute mountain sickness
      (AMS). Cerebral blood flow is elevated in acute hypoxia exposure in humans, but
      the response in this setting of cerebral blood volume is unknown. After
      discussing the background, attention is given to noninvasive measurement of
      cerebral blood volume, and recent preliminary data on cerebral blood volume in
      AMS

PMID- 14713121
TI  - Ventilation, autonomic function, sleep and erythropoietin. Chronic mountain
      sickness of Andean natives.
AB  - Polycythemia is one of the key factors involved in the chronic mountain sickness
      syndrome, a condition frequent in Andean natives but whose causes still remain
      unclear. In theory, polycythemia may be secondary to abnormalities in
      ventilation, occurring during day or night (e.g. due to sleep abnormalities)
      stimulating excessive erythropoietin (Epo) production, or else it may result from
      either autogenous production, or from co-factors like cobalt. To assess the
      importance of these points, we studied subjects with or without polycythemia,
      born and living in Cerro de Pasco (Peru, 4330m asl, CP) and evaluated the
      relationship between Epo and respiratory variables both in CP and sea level. We
      also assessed the relationship between sleep abnormalities and the circadian
      rhythm of Epo. Polycythemic subjects showed higher Epo in all conditions, lower
      SaO2 and hypoxic ventilatory response, higher physiological dead space and higher
      CO2, suggesting ventilatory inefficiency. Epo levels could be highly modified by
      the level of oxygenation, and were related to similar directional changes in
      SaO2. Cobalt levels were normal in all subjects and correlated poorly with
      hematologic variables. The diurnal variations in Epo were grossly abnormal in
      polycythemic subjects, with complete loss of the circadian rhythm. These
      abnormalities correlated with the levels of hypoxemia during the night, but not
      with sleep abnormalities, which were only minor even in polycythemic subjects.
      The increased Epo production is mainly related to a greater ventilatory
      inefficiency, and not to altered sensitivity to hypoxia, cobalt or sleep
      abnormalities. Improving oxygenation can represent a possible therapeutic option
      for this syndrome.

PMID- 14713122
TI  - Cardio-pulmonary interactions at high altitude. Pulmonary hypertension as a
      common denominator.
AB  - The purpose of this review is to find the evidence that a disproportionate
      pulmonary vasoconstriction persisting for days, weeks and years during residence
      at high altitude is the common pathophysiologic mechanism of high altitude
      pulmonary edema (HAPE), subacute mountain sickness and chronic mountain sickness.
      A recent finding in early HAPE suggests that transmission of excessively elevated
      pulmonary artery pressure to the pulmonary capillaries leading to alveolar
      hemorrhage as the pathophysiologic mechanism of HAPE. The elevated incidence of
      HAPE in Indian soldiers led the Indian Army to extend the acclimatization period
      from a few days to 5 weeks. Using this protocol, HAPE was prevented, but after
      several weeks of residence at an altitude of 6000m dyspnea, anasarca and pleuro
      pericardial effusion developed. Clinical examination revealed severe congestive
      right heart failure. This condition has been previously described in long-term
      high altitude residents of the Himalaya and the Andes. In rats, smooth muscle
      cells appear in normally non-muscular arterioles within days of simulated
      altitude. Rapid remodeling of the small precapillary arteries may prevent HAPE
      but increase pulmonary vascular resistance leading to pulmonary hypertension in
      long-term high altitude residents. Symptoms and signs of HAPE, subacute mountain
      sickness and chronic mountain sickness reverse completely after residents are
      transfered to low altitude. In conclusion, these findings strongly suggest that
      pulmonary hypertension at high altitude, which could be named "high altitude
      pulmonary hypertension", is the principal and common pathogenic factor of all
      three cardio-pulmonary manifestations of high altitude illness. Accordingly,
      subacute mountain sickness and chronic mountain sickness could be renamed in
      "acute-" and "chronic right heart failure of high altitude", respectively.

PMID- 14713123
TI  - Oxidative stress and aging.
AB  - Free radical-derived reactive oxygen species (ROS) are constantly generated in
      most living tissue and can potentially damage DNA, proteins and lipids.
      "Oxidative stress" occurs if ROS reach abnormally high concentrations. Harman was
      the first to propose that the damaging effects of ROS may play a key role in the
      mechanism of aging. Genetic studies of such distantly related species as C.
      elegans, Drosophila melanogaster, and mice support this hypothesis. However, ROS
      are not only a cause of structural damage, but also physiologically important
      mediators in biological signaling processes. Abnormally high levels of ROS may
      therefore lead to dysregulation of redox-sensitive signaling pathways. The redox
      sensitive targets in these pathways are often signaling proteins with redox
      sensitive cysteine residues which are oxidized to sulfenic acid moieties and
      mixed disulfides, thereby altering the signaling function of the protein. Because
      the formation of these mixed disulfides can also occur through a prooxidative
      shift in the intracellular thiol/disulfide redox status (REDST), the respective
      signaling pathways respond not only to ROS but also to changes in REDST.
      Information about the concentration of ROS in living tissue is scarce, but aging
      related changes in REDST are well documented. Several studies with cell cultures
      or experimental animals have shown that the oxidative shift in the intracellular
      glutathione REDST is typically associated with cellular dysfunction.
      Complementary studies in humans have shown that oxidative changes in the plasma
      (i.e., extracellular) REDST are correlated with aging-related pathophysiological
      processes. The available evidence suggests that these changes play a key role in
      various conditions which limit the human life span. Several attempts have been
      made to ameliorate the consequences of aging by thiol-containing antioxidants,
      but this approach requires a detailed knowledge of the effects of thiol
      containing antioxidants on cysteine homeostasis, REDST, and redox-sensitive
      signaling pathways of the host.

PMID- 14713124
TI  - Radical dioxygen: from gas to (unpaired!) electrons.
AB  - Photosynthesising cyanobacteria breathed life into what was 1000 million years
      ago considered a reductive atmosphere, thus providing a selective pressure for
      the evolution of O2-dependent organisms. However, the fact that molecular O2
      exists in air as a free radical renders it a double-edged sword, capable of
      sustaining life in physiologically controlled amounts, yet fatal when in excess.
      The controlled delivery and stepwise reduction in PO2 from air to mitochondrion
      may in itself be considered an evolutionary antioxidant to cope with this
      biological conundrum. The present review will discuss the potential roles, both
      good and bad, for free radicals during human adaptation to altered environmental
      PO2. By combining electron paramagnetic resonance spectroscopy with spin
      trapping, we provide direct molecular evidence for increased O2 and carbon
      centered radical generation at high-altitude which may seem paradoxical in light
      of the reduced PO2. Radical-mediated contributions to tissue damage and their
      subsequent role in the pathogenesis of AMS, HAPE and HACE will also be critically
      examined. Finally, we focus on the sources, mechanisms and functional
      significance of free radical generation in hypoxia, with a brief consideration of
      their more positive role as putative signal transductants, capable of adjusting
      cellular homeostasis and initiating protective adaptation. Our preliminary
      studies in humans suggest that radical generation by skeletal muscle is
      exquisitely sensitive to intracellular PO2 which may provide a unifying theory to
      explain the "free radical paradox" of high-altitude.

PMID- 14713125
TI  - Hypoxic regulation of blood flow in humans. Skeletal muscle circulation and the
      role of epinephrine.
AB  - Vascular tone represents the balance between local vasodilator mechanisms which
      attempt to secure adequate blood flow for metabolic demand and neural
      vasoconstrictor reflexes attempting to maintain arterial pressure. Hypoxia alters
      vascular tone, shifting this balance in complex ways. Hypoxic vascular responses
      are not uniform across vascular beds and the mechanisms of hypoxic vasodilation
      appear to be tissue specific. In healthy humans, skeletal muscle vascular beds
      exhibit a graded vasodilation in response to hypoxia despite increases in
      sympathetic vasoconstrictor nerve activity. Previous studies have documented a
      number of vasodilator substances or systems that appear to be involved in this
      hypoxic vasodilation. My colleagues and I have conducted studies on the extent to
      which sympathetic vasoconstriction can mask hypoxic vasodilation, and how
      sympathetic vasoconstrictor activity interacts with local factors that mediate
      hypoxic vasodilation in humans. We have focused largely on beta-adrenergic
      mediated vasodilation, noting that it produces some of its effects via a nitric
      oxide (NO) pathway. This review will explore the role of epinephrine in
      generating skeletal muscle vasodilation. How the many factors that determine
      vascular tone during hypoxic stress impact on the regulation of arterial pressure
      and how hypoxic vasodilation is altered in several pathophysiological conditions
      will be discussed.

PMID- 14713126
TI  - Hypoxic regulation of blood flow in humans. Alpha-adrenergic receptors and
      functional sympatholysis in skeletal muscle.
AB  - Acute exposure to hypoxia evokes changes in local vasodilator and neural
      vasoconstrictor factors that significantly influence vascular tone. In humans,
      the net effect of acute systemic hypoxia is limb vasodilation despite significant
      reflex increases in muscle sympathetic vasoconstrictor nerve activity and
      norepinephrine spillover. In this context, some studies in experimental animals
      and humans have documented that hypoxia can reduce the vasoconstrictor responses
      to sympathetic nerve stimulation, as well as exogenous alpha-adrenergic agonist
      administration (functional sympatholysis). In contrast, other studies have
      provided evidence that sympathetic vasoconstriction is well preserved during
      hypoxia. Recently, our laboratory demonstrated that local blockade of alpha
      adrenergic receptors significantly augments the forearm vasodilator response to
      hypoxia, indicating that sympathetic vasoconstriction persists and can restrain
      skeletal muscle blood flow under these conditions. Therefore, we revisited this
      issue and performed a study designed to test the hypothesis that forearm
      vasoconstrictor responses to local endogenous norepinephrine release are not
      reduced during systemic hypoxia in humans. To do so, we used selective intra
      arterial infusions tyramine to evoke local endogenous norepinephrine release and
      measured the forearm vasoconstrictor responses during various levels of hypoxia
      (85, 80, and 75 % O2 saturation). Our findings demonstrate that forearm post
      junctional alpha-adrenergic vasoconstrictor responsiveness is well preserved
      during systemic hypoxia in healthy humans. The implications of these findings
      with respect to arterial blood pressure regulation and functional sympatholysis
      in skeletal muscle are discussed.

PMID- 14713127
TI  - Hypoxic regulation of blood flow in humans. Skin blood flow and temperature
      regulation.
AB  - Regulation of cutaneous vascular tone in humans is complex due to the different
      types of skin in various regions of the body and the vast array of nerves
      involved in regulation of blood flow. Due to these complexities, it is unclear
      how the cutaneous vasculature responds to hypoxia. There are reports of
      exaggerated vasoconstriction and vasodilation, while others suggest the skin is
      unresponsive to a hypoxic stimulus. Preliminary work in our laboratory suggests
      hypoxic vasodilation may be unmasked with alpha-receptor blockade. In contrast to
      skeletal muscle, hypoxic cutaneous vasodilation is not blunted by beta-blockade,
      but may be abolished with NO-synthase inhibition. Furthermore, effects of hypoxia
      on skin blood flow may be more pronounced during combined hypoxic and
      thermoregulatory challenges. Along these lines, overall thermoregulation may be
      impacted by hypoxic effects on the cutaneous vasculature and hypobaric effects on
      sweating and evaporation. During supine heat stress, for example, skin blood flow
      can increase to 8 Liters per minute. This dramatic rise in skin blood flow is
      accomplished by an increase in cardiac output and redistribution of blood flow
      from the splanchnic and renal vascular beds. During hypoxia, splanchnic blood
      flow has been shown to increase. Thus, during a hypoxic challenge in the heat, a
      competition for blood flow between the compliant skin and splanchnic regions must
      exist, but is not well understood. In this review, the effects of hypoxia on the
      regulation of cutaneous vascular tone and the impact on temperature regulation
      will be discussed.

PMID- 14713128
TI  - Turning up the heat in the lungs. A key mechanism to preserve their function.
AB  - Life threatening events cause important alterations in the structure of proteins
      creating the urgent need of repair to preserve function and ensure survival of
      the cell. In eukariotic cells, an intrinsic mechanism allows them to defend
      against external stress. Heat shock proteins are a group of highly preserved
      molecular chaperones, playing a crucial role in maintaining proper protein
      assembly, transport and function. Stress-induced upregulation of heat shock
      proteins provides a unique defense system to ensure survival and function of the
      cell in many organ systems during conditions such as high temperature, ischemia,
      hypoxia, inflammation, and exposure to endotoxin or reactive oxygen species.
      Induction of this cellular defense mechanism prior to imposing one of these
      noxious insults, allows the cell/organ to withstand a subsequent insult that
      would otherwise be lethal, a phenomenon referred to as "thermo-tolerance" or
      "preconditioning". In the lung, stress-induced heat shock protein synthesis, in
      addition to its cyto-protective and anti-inflammatory effect, helps to preserve
      vectorial ion transport and alveolar fluid clearance. In this review, we describe
      the function of heat shock proteins in the lung, with particular emphasis on
      their role in the pathophysiology of experimental pulmonary edema, and their
      potential beneficial effects in the prevention and/or treatment of this life
      threatening disease in humans.

PMID- 14713129
TI  - Proteins involved in salvage of the myocardium.
AB  - In the Western world, cardiac ischemic disease is still the most common cause of
      death despite significant improvements of therapeutic drugs and interventions.
      The fact that the heart possesses an intrinsic protection mechanism has been
      systematically overlooked before the 1980s. It has been clearly shown that the
      activation of this mechanism can reduce the infarct size after an ischemic
      insult. Prerequisite is the induction of the synthesis of such cardio-protective
      proteins as heat shock proteins (HSPs) and anti-oxidative enzymes. HSPs are
      involved in the maintenance of cell homeostasis by guiding the synthesis, folding
      and degradation of proteins. Besides, the various family members cover a broad
      spectrum of anti-oxidative, anti-apoptotic and anti-inflammatory activities.
      Although the major inducible HSP72 has received most attention, other HSPs are
      able to confer cardioprotection as well. In addition, it seems that there is a
      concerted action between the various cardio-protective proteins. One drawback is
      that the beneficial effects of HSPs seem to be less effective in the compromised
      than in the normal heart. Although clinical studies have shown that there is a
      therapeutic potential for HSPs in the compromised heart, major efforts are needed
      to fully understand the role of HSPs in these hearts and to find a safe and
      convenient way to activate these protective proteins.

PMID- 14713130
TI  - The NO - K+ channel axis in pulmonary arterial hypertension. Activation by
      experimental oral therapies.
AB  - The prognosis of patients with pulmonary arterial hypertension (PAH) is poor.
      Available therapies (Ca(++)-channel blockers, epoprostenol, bosentan) have
      limited efficacy or are expensive and associated with significant complications.
      PAH is characterized by vasoconstriction, thrombosis in-situ and vascular
      remodeling. Endothelial-derived nitric oxide (NO) activity is decreased,
      promoting vasoconstriction and thrombosis. Voltage-gated K+ channels (Kv) are
      downregulated, causing depolarization, Ca(++)-overload and PA smooth muscle cell
      (PASMC) contraction and proliferation. Augmenting the NO and Kv pathways should
      cause pulmonary vasodilatation and regression of PA remodeling. Several
      inexpensive oral treatments may be able to enhance the NO axis and/or K+ channel
      expression/function and selectively decrease pulmonary vascular resistance (PVR).
      Oral L-Arginine, NOS' substrate, improves NO synthesis and functional capacity in
      humans with PAH. Most of NO's effects are mediated by cyclic guanosine
      monophosphate (c-GMP). cGMP causes vasodilatation by activating K+ channels and
      lowering cytosolic Ca++. Sildenafil elevates c-GMP levels by inhibiting type-5
      phosphodiesterase, thereby opening BK(Ca). channels and relaxing PAs. In PAH,
      sildenafil (50 mg-po) is as effective and selective a pulmonary vasodilator as
      inhaled NO. These benefits persist after months of therapy leading to improved
      functional capacity. 3) Oral Dichloroacetate (DCA), a metabolic modulator,
      increases expression/function of Kv2.1 channels and decreases remodeling and PVR
      in rats with chronic-hypoxic pulmonary hypertension, partially via a tyrosine
      kinase-dependent mechanism. These drugs appear safe in humans and may be useful
      PAH therapies, alone or in combination.

PMID- 14713131
TI  - Non-erythroid functions of erythropoietin.
AB  - The oxygen-dependent, renal cytokine eythropoietin (Epo) is well known to
      increase red cell production. Binding of Epo to the Epo receptor (EpoR) represses
      apoptosis of erythroid progenitor cells, thereby allowing their final maturation.
      We and others showed that Epo and its receptor are expressed in many other
      tissues, including brain, spinal cord, retina and testis. The presence of a blood
      barrier suggests that Epo plays a local role in these organs. Indeed,
      therapeutically applied or hypoxically induced Epo has been shown to reduce the
      infarct volume in various stroke animal models, to prevent retinal degeneration,
      and to ameliorate spinal cord injury. In a study conducted by Ehrenreich and
      colleagues, stroke patients treated with Epo showed reduced infarct volume, fast
      neurological recovery and improved clinical outcome. In analogy to its function
      on erythroid progenitor cells, this neuroprotective effect of Epo might be
      explained by repression of programmed cell death. Apart from neuroprotection,
      there is an assumption that Epo present in breast milk has the potential to
      protect against mother-to-infant transmission of HIV. When using Epo at high
      doses for longer time periods; however, care has to be taken to control the
      resulting chronic polycythemia that most probably caused enlarged cerebral
      infarct volumes in a transgenic mouse model that due to Epo-overexpression
      reached hematocrit levels of about 0.8. Overall, these data strongly support the
      notion that Epo will soon find new applications in the clinic.

PMID- 14713132
TI  - Peter Hochachka and oxygen.

PMID- 14713133
TI  - Proposal for scoring severity in chronic mountain sickness (CMS). Background and
      conclusions of the CMS Working Group.

PMID- 14713134
TI  - Epidemiological modeling of acute mountain sickness (AMS). A prospective data
      collection standard.

PMID- 14713136
TI  - Posttraumatic stress disorder among Hispanic and African-American drug users.
AB  - CONTEXT: Treating high-risk substance abusers who are members of minority groups
      may require varied protocols depending on differences among minority groups.
      OBJECTIVES: To explore cocaine abuse (CA)/ dependence with physiological
      dependence (CDPD) and posttraumatic stress disorder (PTSD) diagnosis differences
      between out-of-treatment Hispanic and African American adults, in order to
      identify cultural differences in how experiences and attitudes affect cocaine use
      behaviors. DESIGN, SETTING, AND PARTICIPANTS: This study uses data collected
      between February and November 2000, as part of a three-year longitudinal study. A
      cohort of 347 out-of-treatment, Hispanic and African American cocaine-using
      adults from the Houston metropolitan area were interviewed to measure differences
      between cocaine users who are dually diagnosed and those that are not. MAIN
      OUTCOME MEASURES: Meeting the Diagnostic and Statistical Manual of Mental
      Disorders, 4th ed. criteria for dual diagnoses of CA/PTSD or CDPD/PTSD. RESULTS:
      For the dual diagnoses categories, 102 (29%) participants met the requirements
      for CA/PTSD or CDPD/PTSD. Logistic regression models were used, with CA/PTSD and
      CDPD/PTSD as the dependent variables. Age, race, gender, and income were used as
      the independent variables. Results indicate that individuals with higher income
      have a greater probability of developing CA/PTSD (beta = 0.919, p < 0.05). For
      both dual diagnoses categories of CA/PTSD and CDPD/ PTSD, results indicate that
      being female increases the likelihood of developing both of these dual diagnoses,
      (beta = 2.106, p < 0.05) or (beta = 2.510, p < 0.05). However, being an older
      female decreases the probability that an individual would develop these dual
      diagnoses (beta = -2.227, p < 0.05) (beta = -2.577, p < 0.05). CONCLUSIONS: No
      differences were found for race/ethnicity among the dually diagnosed Hispanics
      and African Americans, however, gender differences were found. Being female
      increases an individual's probability of developing a dual diagnosis of CA/PTSD
      or CDPD/PTSD. In addition to being female, being a young female further increases
      an individual's probability of being dually diagnosed.

PMID- 14713135
TI  - Prediction of treatment outcome by baseline urine cocaine results and self
      reported cocaine use for cocaine and opioid dependence.
AB  - This study examined the usefulness of baseline cocaine urine toxicology results
      and self-reported days of cocaine use in predicting treatment response in cocaine
      and opioid-dependent subjects. Ninety-nine male and 52 female subjects,
      maintained on buprenorphine, participated in a 24-week, randomized, double-blind,
      four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency
      management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had
      cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of
      treatment. For the previous 30 days before study participation, 91 (60%) subjects
      reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%)
      subjects reported more than 15 days (high baseline cocaine use). By using the
      treatment effectiveness score (TES) as the outcome measure, a negative urine for
      cocaine at baseline predicted a better outcome during a 24-week trial for cocaine
      and opioid use. There also was a significant interaction between baseline cocaine
      urine results and desipramine response with the urine cocaine-negative group
      showing greater desipramine response than placebo for opioid and cocaine use.
      Self-reported cocaine use at baseline did not show significant predictive power
      for TES scores during the clinical trial. These results suggest that baseline
      cocaine urine results should be considered as stratifying variables in clinical
      trials for cocaine dependence.

PMID- 14713137
TI  - Children of mothers with serious substance abuse problems: an accumulation of
      risks.
AB  - This study examines the life circumstances and experiences of 4084 children
      affected by maternal addiction to alcohol or other drugs. The paper will address
      the characteristics of their caregivers, the multiple risk factors faced by these
      children, their health and development, and their school performance. Data were
      collected from mothers at intake into 50 publicly funded residential substance
      abuse treatment programs for pregnant and parenting women. Findings from this
      study suggest that children whose mothers abuse alcohol or other drugs confront a
      high level of risk and are at increased vulnerability for physical, academic, and
      socioemotional problems. Children affected by maternal addiction are in need of
      long-term supportive services.

PMID- 14713138
TI  - Improving on-time counseling attendance in a methadone treatment program: a
      contingency management approach.
AB  - Two studies were conducted to investigate the effectiveness of contingency
      management techniques in promoting punctual counseling attendance among methadone
      maintenance patients. In Study 1, 50 participants were recruited from an inner
      city methadone maintenance program. Study 1 used an A-B-A design with baseline,
      intervention, and return-to-baseline phases. On-time attendance was reinforced
      during the intervention phase with a voucher that was redeemable for a draw out
      of a box containing 100 tokens with values varying from 0.00 dollars to 100.00
      dollars. Methadone maintenance patients who exhibited poor attendance during
      baseline showed a significant positive response during the contingency management
      intervention phase. Study 2 used the same design as Study 1 except that the 52
      participants were randomized into reinforcement groups that received either the
      variable rate of reinforcement as in Study 1 or a fixed value reinforcer of 3.25
      dollars. As in Study 1, Poor Attenders significantly improved counseling
      attendance during the intervention. There were no differences between the
      variable and fixed reinforcement groups. Overall, results suggest that targeting
      Poor Attenders with contingency management techniques may be a cost-effective
      method of improving counseling attendance. Targeting Poor Attenders early in
      treatment may be especially important for improving treatment outcomes.

PMID- 14713139
TI  - Psychiatric illness among drug court probationers.
AB  - The purpose of this study was to identify the level of psychiatric symptoms
      reported by probationers involved with a drug court in Hennepin County,
      Minnesota. Sixty probationers completed a brief demographic interview, the Beck
      Depression and Anxiety Inventories (BDI and BAI) and a measure of medical quality
      of life. Fifteen participants completed a structured interview for psychiatric
      diagnosis (SCID-I). The sample was predominantly male, African American, and
      unemployed. Over 40% had received treatment for psychiatric problems, including
      20% who reported a history of inpatient psychiatric admission and 15% currently
      taking a psychotropic medication. More than 1/3 of BDI and BAI scores were
      moderate to severe. The mean Short Form (SF)-36 scores were significantly lower
      than in the general population. Trends suggested more distress associated with:
      Caucasian race, female gender, less education, unemployment, and less previous
      legal involvement. Of 15 participants that completed a SCID-I, 13 participants
      met lifetime diagnostic criteria for at least one psychiatric disorder. The most
      common diagnoses were major depressive disorder and posttraumatic stress disorder
      (PTSD). Three participants met diagnostic criteria for current psychotic
      disorder. Half of participants who currently met criteria for a disorder reported
      that they had never received psychiatric treatment. Results indicate participants
      currently were experiencing high rates of emotional symptoms. Serious mental
      illness was common. Many of these individuals had not been identified previously
      as needing psychiatric treatment. More frequent and thorough screening for
      psychiatric illness in drug court settings is necessary to identify serious
      psychiatric illnesses.

PMID- 14713140
TI  - Changes in substance use associated with emergency room and primary care services
      utilization in the United States general population: 1995-2000.
AB  - OBJECTIVE: The purpose of this study was to compare changes in the prevalence of
      heavy problem drinking and drug use among those obtaining emergency room (ER),
      primary care, and other health care services between 1995 and 2000 in the U.S.
      general population. METHOD: Data analyzed are from the Alcohol Research Group's
      1995 (n = 4925) and 2000 (n = 7612) National Alcohol Surveys. Data for the 1995
      survey was based on face-to-face interviews in respondents' homes in the 48
      contiguous states, while the 2000 interview was a random-digit dialing computer
      assisted telephone interview of the household population in all 50 states.
      RESULTS: Those reporting any health services utilization were less likely to
      report heavy drinking, two or more alcohol problems, and symptoms of alcohol
      dependence during the previous year in 2000 compared with 1995, but heavy or
      problem drinking was not predictive of health services utilization at either
      time. Controlling for demographic characteristics and health insurance coverage,
      illicit drug users were almost twice as likely [odds ratio (OR) = 1.85] compared
      with nonusers, to report ER utilization, and one and a half times more likely (OR
      = 1.55) to report primary care utilization during the past year in the 2000
      survey, but drug use was not significantly predictive of health services
      utilization in 1995. CONCLUSIONS: These data suggest that while those alcohol
      involved individuals were no more likely than others to use ER and primary care
      services in either 1995 or 2000, those drug-involved individuals were more likely
      to do so in 2000, perhaps related to the fact that these individuals may be
      incurring more health problems associated with their drug use that require
      medical attention. While identification and intervention with problem drinkers in
      clinical settings has received a great deal of attention, drug users may be
      overrepresented in health service settings, and such settings also may provide a
      window of opportunity for screening and intervention for a reduction in drug
      related problems.

PMID- 14713141
TI  - Outcomes of a federally funded program for alcohol and other drug prevention in
      higher education.
AB  - This paper presents the results of the Nationwide Campuses Study that measure the
      impact of programs supported by the Fund for the Improvement of Postsecondary
      Education (FIPSE) for collegiate alcohol and other drug (AOD) prevention efforts.
      Outcomes were measured by using standardized pre- and post-program items on the
      Core Alcohol and Drug Survey and adjusted prevalences of AOD use. Although
      student awareness of AOD prevention programs increased during the funding period,
      there also were increases in the desire for drugs at parties and in the
      frequencies of arrests for driving while intoxicated or under the influence and
      of poor academic performance. Adjusted prevalences of alcohol, marijuana, and
      cocaine use among students increased, while tobacco use decreased. Curriculum
      infusion, administrative response, and faculty and community activities most
      clearly were associated with favorable outcomes. Overall, however, FIPSE funding
      had limited short-term impact on AOD use and its consequences in higher
      education.

PMID- 14713142
TI  - Longitudinal perspective: adverse childhood events, substance use, and labor
      force participation among homeless adults.
AB  - OBJECTIVES: We examined the long-term effects of adverse childhood events on
      adulthood substance use, social service utilization, and subsequent labor force
      participation. METHODS: A county-wide probability sample of 397 homeless adults
      was interviewed three times in a 15-month period. By using a path model,
      literature-based relationships between adverse childhood events and labor force
      participation with the mediating effects of adulthood substance use and service
      use were tested. RESULTS: Adverse childhood events were precursors to adulthood
      alcohol and drug use. Consistent substance use was negatively associated with
      long-term labor force participation and with social service utilization among
      homeless adults. Adverse events at childhood, however, were positively associated
      with service use. CONCLUSIONS: Adverse childhood events may contribute to
      negative adulthood consequences, including consistent substance use and reduced
      labor force participation. Agencies that are involved in halting the abuse or
      neglect also should participate in more preventive interventions. Job-related
      assistance is particularly important to facilitate employment and labor force
      participation among homeless adults.

PMID- 14713143
TI  - Integrating medical and substance abuse treatment for addicts living with
      HIV/AIDS: evidence-based nursing practice model.
AB  - Forty-five active substance abusers with HIV/AIDS voluntarily participated in a
      substance abuse treatment research study with interviews at intake, 6 months and
      12 months. These participants were engaged in treatment for a minimum of 45 days
      and a maximum of 90 days. The study used a nursing model of care, The
      Personalized Nursing LIGHT model, to integrate treatment for HIV/AIDS with
      substance abuse treatment. The LIGHT model seeks to enhance patient well being
      directly and thereby to support interventions that decrease substance use and
      improve management of chronic disease. The substance abuse treatment team
      included a nurse who used the LIGHT model and coordinated an integrated care
      protocol. The nurse accompanied clients on visits to their physicians for HIV
      treatment and facilitated the integration of medical recommendations with the
      substance abuse treatment. Six-month posttest data were gathered on all 45
      participants and 12-month posttest interviews were accomplished with 29 of them.
      At 6 months, 78% of the respondents (35/45) reported no drug use in the past 30
      days, and, at 12 months, 79% (23/29) were drug free for the past month.
      Significant decreases from intake to 6 months were detected on Addiction Severity
      Index (ASI) composite scores for drug use (p < 0.01), alcohol use (p < 0.04),
      medical severity (p < 0.02), psychiatric severity (p < 0.01), legal problems (p <
      0.04), and employment difficulty (p < 0.01). Improvement of 6-month drug use
      composite scores was related significantly to treatment duration (R = 0.42; p <
      0.01). Significant decreases in ASI measures of drug use (p < 0.01), alcohol use
      (p < 0.01), employment difficulty (p < 0.01), and family/social problems (p <
      0.01) also occurred at 12 months. Well being, as measured by a Global Well Being
      Index, was found to improve significantly at 6 months (p < 0.02) and 12 months (p
      < 0.07). Concurrently, significant improvement was observed on Medical Outcomes
      Study-36-Item Short-Form Health Survey (SF-36) measures of general health and
      health functioning. These changes were noted at 6 months in the general health (p
      < 0.02), mental health (p < 0.01), social functioning (p < 0.01), role/emotional
      status (p < 0.04), and vitality (p < 0.01) subscales. At 12 months, the social
      functioning (p < 0.01) subscale responses were further decreased.

PMID- 14713144
TI  - Differential prediction of alcohol use and problems: the role of biopsychological
      and social-environmental variables.
AB  - This study examined the differential prediction of alcohol use and problems by
      biopsychological (i.e., affective and cognitive variables) and social
      environmental (i.e., social norms) variables. Undergraduate students (N = 231)
      were assessed twice separated by a 30-day interval. Time 1 impulsivity, affect
      lability, social norms, and perceived conflict between personal strivings and
      alcohol use were each significant predictors of alcohol use-related problems at
      Time 2 (T2). Structural equation models indicated that impulsivity and affect
      lability were related directly with use-related problems, while social norms and
      use-strivings conflict were related indirectly with use-related problems
      (mediated by use frequency). Impulsivity moderated the T2 use to use-related
      problems relationship. Use frequency was associated more strongly with use
      related problems among more impulsive participants.

PMID- 14713145
TI  - The influence of gender on factors associated with HIV transmission risk among
      young Russian injection drug users.
AB  - HIV infection rates are dramatically increasing in the Russian Federation.
      Epidemiological studies indicate that the greatest rise of HIV incidence has been
      among injection drug users (IDU). Young adults (N = 188) who reported injecting
      drug use completed surveys and interviews that assessed injection drug use
      behavior, sexual behavior, and HIV-related knowledge. The average age of
      participants was 21.3 years. Multiple linear regression analysis found male
      gender and younger age at sexual debut was positively and significantly
      associated with having multiple sexual partners. Gender moderated the effects of
      sexual debut and number of times injected drugs were used in the past month.
      Males who initiate sex at a younger age were more likely to report multiple sex
      partners and females who reported higher frequency of drug use were more likely
      to report multiple sex partners. Gender is an important factor, as well as
      moderator of risk behavior among Russian injection drug users. Delaying sexual
      debut, particularly for males, may be an effective strategy to reduce subsequent
      risk behavior. Prevention efforts among IDUs need to address sexual risk behavior
      in conjunction with injection risk behavior.

PMID- 14713146
TI  - Induction of antimicrobial 3-deoxyflavonoids in pome fruit trees controls fire
      blight.
AB  - Fire blight, a devastating bacterial disease in pome fruits, causes severe
      economic losses worldwide. Hitherto, an effective control could only be achieved
      by using antibiotics, but this implies potential risks for human health,
      livestock and environment. A new approach allows transient inhibition of a step
      in the flavonoid pathway, thereby inducing the formation of a novel antimicrobial
      3-deoxyflavonoid controlling fire blight in apple and pear leaves. This compound
      is closely related to natural phytoalexins in sorghum. The approach does not only
      provide a safe method to control fire blight: Resistance against different
      pathogens is also induced in other crop plants.

PMID- 14713147
TI  - Externally accumulated flavonoids in three Mediterranean Ononis species.
AB  - The Mediterranean Ononis species, O. fruticosa, O. natrix subsp. ramosissima and
      O. tridentata, have been analyzed for their exudate flavonoids. More than 20
      flavonoid aglycones were identified, some of which are rather rare natural
      compounds. One of them, namely hypolaetin-8,3',4'-trimethyl ether, had been found
      only once before. The results are presented in a table along with literature
      data, and the chemotaxonomic impact of the flavonoid patterns is discussed.

PMID- 14713148
TI  - Quinolizidine alkaloid profiles of two taxa of Teline maderensis.
AB  - The alkaloid composition of the aerial parts of two taxa of Teline maderensis was
      studied by capillary GLC and GLC-MS. N-Methylcytisine was the major alkaloid
      found in both plants. Contents of cytisine and lupanine were higher in T.
      maderensis var. paivae while anagyrine content was more pronounced in T.
      maderensis var. maderensis. The alkaloids dehydrocytisine, N-acetylcytisine and
      epibaptifoline appeared only in T. maderensis var. maderensis and N
      formylcytisine was identified as a minor constituent in T. maderensis var.
      paivae, and detected only in trace amounts in the other variety of the plant.

PMID- 14713149
TI  - Comparative analysis of the composition of flower volatiles from Lamium L.
      species and Lamiastrum galeobdolon Heist. ex Fabr.
AB  - The volatiles of fresh flowers from nine natural populations of four Lamium
      species and Lamiastrum galeobdolon were analyzed by GC/MS. 49 compounds, 43 of
      them new for Lamium and Lamiastrum, were identified. The studied samples showed
      similarity of the volatile profiles and dependence of the oil-composition on the
      collection site. Significant amounts of squalene were found in all samples. The
      presence of homological series of straight chain alkanes from C12 to C31 was
      shown. Phenethyl alcohol was found only in L. maculatum f. alba.

PMID- 14713150
TI  - Lipophylic compounds from Euphorbia peplis L.--a halophytic plant from the
      Bulgarian Black Sea coast.
AB  - The chemical composition of the lipophylic fraction from the halophytic plant
      Euphorbia peplis L. was investigated. Compared to other terrestrial higher plants
      an increase of triacylglycerols and especially of glycolipids was observed. The
      main phospholipid was phosphatidyl choline, followed by almost equal
      concentrations of phosphatidyl ethanolamine and phosphatidyl glycerol. A
      relatively high concentration of phosphatidic acids (6.5% of the total
      phospholipids) was found. The main sterol appeared to be sitosterol and
      significant amounts of tetracyclic triterpene alcohols were found. The
      composition of the volatile compounds is relatively simple and only one
      chlorinated compound, identified as 2,2-diethoxy-1-chloroethane, was found. There
      was a strong toxicity of the total lipophylic extract towards Artemia salina.

PMID- 14713151
TI  - Root constituents of Cichorium pumilum and rearrangements of some lactucin-like
      guaianolides.
AB  - Two eudesmanolides, eight lactucin-like guaianolides and five phenolic compounds
      were isolated for the first time from roots of Cichorium pumilum, along with two
      previously reported eudesmane-type sesquiterpene lactones. Rearrangements of some
      lactucin-like guaianolides during isolation procedures were also discussed.

PMID- 14713152
TI  - Germacrane derivatives from Santolina pinnata subsp. neapolitana.
AB  - From the aerial parts of Santolina pinnata subsp. neapolitana, one new and four
      known germacrane derivatives were isolated. The new compound was characterized as
      1alpha,10beta-epoxy-7alphaH-germacr-4(15)-ene-2/beta5alpha,6beta-triol by
      spectral methods.

PMID- 14713153
TI  - Analysis of the volatile components of five Turkish Rhododendron species by
      headspace solid-phase microextraction and GC-MS (HS-SPME-GC-MS).
AB  - Volatile constituents of various solvent extracts (n-hexane, CH2Cl2, H2O) of 15
      different organs (leaves, flowers, fruits) of five Rhododendron species
      (Ericaceae) growing in Turkey were trapped with headspace solid-phase
      microextraction (HS-SPME) technique and analyzed by GC-MS. A total of 200
      compounds were detected and identified from organic extracts, while the water
      extracts contained only traces of few volatiles. The CH2Cl2 extract of the R.
      luteum flowers was found to exhibit the most diverse composition: 34 compounds
      were identified, with benzyl alcohol (16.6%), limonene (14.6%) and p-cymene
      (8.4%) being the major compounds. The CH2Cl2-solubles of R. x sochadzeae leaves
      contained only phenyl ethyl alcohol. This study indicated appreciable intra
      specific variations in volatile compositions within the genus. Different
      anatomical parts also showed altered volatile profiles. This is the first
      application of HS-SPME-GC-MS on the volatiles of Rhododendron species.

PMID- 14713154
TI  - Volatile composition of Jasonia glutinosa D. C.
AB  - Using GC-MS the volatile composition of Jasonia glutinosa D. C., was studied by
      comparing two different methods for the isolation of a volatile fraction:
      distillation from the fresh plant in order to obtain the essential oil, and
      direct thermal desorption (DTD). Compared with essential oil extraction the main
      advantages of the DTD technique are the smaller sample amount required, and the
      increased range of volatile compounds which can be subsequently analysed by GC
      MS.

PMID- 14713155
TI  - Acetylation and silylation of piperidine solubilized sporopollenin from pollen of
      Typha angustifolia L.
AB  - Silyl and acetyl derivatives of sporopollenin from the pollen of Typha
      angustifolia L. were prepared. The derivatized products were readily soluble in
      piperidine-d11 and could be investigated employing one- and two-dimensional
      proton and carbon NMR (nuclear magnetic resonance) spectroscopy (1H,1H-COSY and
      13C,1H-HETCOR techniques). For the first time, a two dimensional 13C,1H-HETCOR
      NMR spectrum of a sporopollenin could be obtained. The results underline the
      importance of derivatization techniques for obtaining two dimensional 13C-NMR
      spectra of sporopollenins. Moreover, piperidine turns out to be a more suitable
      solvent for sporopollenins than 2-aminoethanol, as it allows for higher
      solubilities, being important for 2D-NMR investigations. From the HETCOR and COSY
      spectra of the silylated and the acetylated Typha samples the occurrence of
      aliphatic polyhydroxy compounds as well as phenolic OH groups became evident.

PMID- 14713156
TI  - First evidence for the presence of weddellite crystallites in Opuntia ficus
      indica parenchyma.
AB  - Calcium oxalate crystallites occur very often in the plants tissues and their
      role is still poorly known. We report here the experimental protocol leading to
      the isolation of two forms of calcium oxalate crystallites differing in their
      hydration level in the parenchymal tissues of Opuntia ficus indica (Miller).
      Whereas the whewellite crystallites are habitual in all Opuntia species, the
      weddellite form has never been isolated from these species before, which is
      probably due to their small size (about 1 microm). We have identified these forms
      using X-ray diffraction and scanning electron microscopy.

PMID- 14713157
TI  - Silphiperfolane sesquiterpene acids from Artemisia chamaemelifolia Vill.
AB  - The aerial parts of Artemisia chamaemelifolia Vill. afforded, in addition to five
      known sesquiterpene acids, a new 5-epi-cantabrenolic acid (6).

PMID- 14713158
TI  - Phenylethanoid glycosides from Phlomis integrifolia Hub.-Mor.
AB  - Two new phenylethanoid glycosides integrifoliosides A (2) and B (3), along with a
      known phenylethanoid glycoside alyssonoside (1) and a flavone glucoside
      chrysoeriol-7-O-beta-D-glucopyranoside (4) were isolated from the aerial parts of
      Phlomis integrifolia. The structures of the new compounds were identified as 3,4
      dihydroxy-beta-phenylethoxy-O-beta-D-apiofuranosyl-(1 --> 4)-alpha-L
      rhamnopyranosyl-(1 --> 3)-4-O-feruloyl-beta-D-glucopyranoside (2) and 3-hydroxy-4
      methoxy-beta-phenylethoxy-O-beta-D-apiofuranosyl-(1 --> 4)-alpha-L
      rhamnopyranosyl-(1 --> 3)-4-O-feruloyl-beta-D-glucopyranoside (3), on the basis
      of spectroscopic (UV, IR, 1D- and 2D-NMR, and HR-FABMS) methods.

PMID- 14713159
TI  - Chemical composition of the essential oil of Phlomis linearis Boiss. & Bal., and
      biological effects on the CAM-assay: a safety evaluation.
AB  - Phlomis linearis Boiss. & Bal. of the Lamiaceae family growing in central, east
      and southeast Anatolia is an endemic species for Turkey. The essential oil
      obtained from the aerial parts by hydro distillation was subsequently analyzed by
      GC/MS. The main components of the oil were found as beta-caryophyllene (24.2%),
      germacrene D (22.3%) and caryophyllene oxide (9.2%), among 49 identified
      compounds, representing 94.5% of the total essential oil. The overall biological
      activity of the essential oil (100 microg/pellet) was tested on the
      chorioallantoic membrane (CAM) of the fertilized hen's egg in order to examine
      the anti-angiogenic and anti-inflammatory activity. None of the tests showed
      pronounced activity, toxicity or irritation at the tested concentration.

PMID- 14713160
TI  - In vitro anti-inflammatory effect of Carthamus lanatus L.
AB  - The anti-inflammatory activity of four total extracts, their fractions and two
      main constituents (alpha-bisabolol beta-D-fucopyranoside and luteolin 7-O
      glucoside) of Carthamus lanatus L. aerial parts, were assessed in vitro by
      determining the inhibitory effects on induced human neutrophils. The
      dichloromethane extract and its water-alcoholic part exhibited the most
      significant inhibitory effects.

PMID- 14713161
TI  - Clastogenic effect of Carthamus lanatus L. (Asteraceae).
AB  - The clastogenic effect of total dichloromethane, methanol and water extracts,
      four bioactive fractions and three individual constituents from Carthamus lanatus
      aerial parts were evaluated in mice by bone marrow chromosome aberration assay
      with mitomycin C as positive control. Significant differences in the percentage
      of aberrant mitosis of the extracts were observed. The dichloromethane extract
      exhibited a considerable clastogenic effect and the water extract a negligible
      one. Different types of chromosome aberrations and time-dependant effects for the
      active fractions and individual compounds were found.

PMID- 14713162
TI  - Investigations of genetic variation between olive (Olea europaea L.) cultivars
      using arbitrarily primed polymerase chain reaction (AP-PCR).
AB  - Characterization and selection of olive clones for the production of olive oil is
      essential in Turkey because of its profitable exploitation. AP-PCR (Arbitrarily
      Primed PCR) is a technique that can distinguish the genetic relationship among
      plant species and other organisms. In this study, AP-PCR approach was used in
      order to determine the genetic relationship of different six olive clones. The
      purity of DNA is one of the most important factors affecting the product of the
      AP-PCR method. In this respect, modified genomic DNA isolation procedure from
      Oleae europaea clones was developed so that this procedure can be used to obtain
      plant genomic DNA from diverse aromatic plants, which produce essential oils and
      secondary metabolites. By following the optimized AP-PCR amplification protocol,
      unique DNA fingerprint profiles for each olive clone were produced. AP-PCR
      generated unique DNA fingerprint profiles can be used in the identification,
      distribution and diversity of various olive cultivars.

PMID- 14713163
TI  - Antioxidative responses of tobacco expressing a bacterial glutathione reductase.
AB  - Reports on stress response of tobacco expressing a bacterial glutathione
      reductase (GR) do not agree. To clarify this situation we investigated several
      parameters using the tobacco BelW3 line and its transformant BelW3gor expressing
      an E. coli GR. This alteration in the activity of GR led to an ambiguous
      modification of the antioxidative system. In contrast to the wild type, the
      transgenic tobacco suffered lipid peroxidation under moderate light intensities,
      while it was found to be more resistant towards oxidative stress induced by
      paraquat or hydrogen peroxide. Transcript levels for violaxanthin deepoxidase and
      cytosolic Cu-Zn-superoxide dismutase were strongly reduced in BelW3gor plants as
      compared to BelW3.

PMID- 14713164
TI  - The antimicrobial activity of extracts of the lichen Cetraria aculeata and its
      protolichesterinic acid constituent.
AB  - In this study, the antimicrobial activity of the acetone, diethyl ether and
      ethanol extracts of the lichen Cetraria aculeata has been investigated. The
      extracts were tested against twelve bacteria and eight fungi and found active
      against Escherichia coli, Staphylococcus aureus, Aeromonas hydrophila, Proteus
      vulgaris, Streptococcus faecalis, Bacillus cereus, Bacillus subtilis, Pseudomonas
      aeruginosa, Listeria monocytogenes. No antimicrobial activity against the fungi
      was detected. It was determined that only one substance in the extracts has
      antimicrobial activity and it was characterized as protolichesterinic acid. The
      MICs of the extracts and protolichesterinic acid were also determined.

PMID- 14713165
TI  - Effects of pesticides on yeasts isolated from agricultural soil.
AB  - The effect of six various pesticides on the growth of yeasts isolated from
      agricultural soil was investigated. Two herbicides (with the effective substances
      lactofen and metazachlor), two fungicides (with the effective substances
      fluquinconazole and prochloraz), and two insecticides (with the effective
      substances cypermethrin + chlorpyrifos and triazamate) were tested. It is evident
      that there are considerable differences in inhibition effects of studied
      pesticides. The fungicide with the effective substance prochloraz inhibited the
      growth of majority of yeast strains. The insecticide triazamate at concentration
      0.6 mM restricted or inhibited growth of all tested strains. The strains of the
      genus Cryptococcus were the most sensitive to pesticides, while the strains of
      the species Cystofilobasidium capitatum, Debaryomyces occidentalis var.
      occidentalis, and Trichosporon cutaneum were the most resistant.

PMID- 14713166
TI  - Pyrrolidonyl and pyridyl alkaloids in Lymantria dispar.
AB  - The occurrence and metabolism of nicotine and related N-containing compounds in
      body fluids of the gipsy moth were addressed. Thin layer chromatographic studies
      clearly showed the simultaneous presence of GABA and 2-pyrrolidone but not of
      GABamide in the larval haemolymph and osmeterial secretion of Lymantria dispar as
      well as in the corresponding body fluids of the saturniids, Saturnia pavonia and
      Attacus atlas. Furthermore, feeding and injection experiments using alkylated
      precursors and combined gas chromatography/mass spectrometry gave evidence of the
      transformation of 2-pyrrolidone to nicotine and of nicotinic acid to nicotinamide
      in caterpillars of L. dispar. Based on these results, on the earlier described
      variation of the secondary-compound patterns of L. dispar during its development,
      and on literature data, metabolic pathways for the hitherto detected pyridyl and
      pyrrolidonyl alkaloids in Lymantriidae (and possibly Saturniidae) are proposed.

PMID- 14713167
TI  - Biological activity of pentachlorophenol on the digestive gland cells of the
      freshwater mussel Unio tumidus.
AB  - Many chlorinated phenols and their derivatives are used extensively as
      insecticides, fungicides and herbicides by industrial and agricultural users
      throughout the world. Among these substances, pentachlorophenol (PCP) is a broad
      spectrum biocide, which is still used as a wood preservative. In this paper, the
      digestive gland cells were used to assess the effect of PCP in the range of
      concentrations 3.75-75 microM (0.01-0.2 ppm) on oxidative DNA damage, fluidity
      changes and peroxidation activity in the plasma membrane. The toxic property of
      PCP on DNA strand breakage was studied using the comet assay. The results showed
      that pentachlorophenol in the range of 37.5-75 microM contributed to these
      lesions. To demonstrate the changes in the fluidity of plasma membrane we used
      the spectrofluorimetric method using two fluorescence probes: 1-[4
      (trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 12-(9
      anthroyloxy) stearic acid (12-AS). It was shown that PC did not influence the
      surface of plasma membrane but contributed to the increase in the fluidity of the
      internal region of the lipid bilayer in the range of concentrations 18.75-75
      microM (0.05-0.2 ppm). We also examined the effect of PCP on the lipid
      peroxidation. To imply its peroxidation properties the spectrophotometry method
      was used to measure the level of malondialdehyde (MDA), one of the endpoints of
      the peroxidation of polyunsaturated fatty acids. The obtained results showed that
      PCP in the used doses did not initiate the formation of lipid peroxides. Thus,
      our investigation indicates that PCP can behave as a prooxidant agent but its
      action depends on the used doses and parameters chosen for the research.

PMID- 14713168
TI  - An alternative structure model for the polypentapeptide in elastin.
AB  - Polypentapeptides (GVGVP)n which are designed in analogy to the connective tissue
      protein elastin are reported to transform various kinds of energy into mechanical
      work by the so-called deltaT(t)-mechanism in cross-linked macroscopic
      polypentapeptide (PPP) films. In the literature, the responsible element of
      conformation in such polypeptides is described as a beta-spiral and the deltaT(t)
      effect is explained as a sudden change of macroconformation of single polypeptide
      molecules from an extended but not regular state below a transition temperature
      T(t) to the beta-spiral above T(t). We examined the secondary structure of the
      linear PPP C(GVGVP)6 in solution with DSC, CD, UV absorption, FTIR and NMR
      spectroscopy. The results suggest that the beta-spiral is not present in the
      conformational structure of the PPP molecules. The antiparallel beta-sheet is
      proposed to be the basic regular part of conformation because it agrees with all
      spectroscopic data. As a consequence, the elasticity of natural elastin must be
      considered from a new perspective.

PMID- 14713169
TI  - Influence of polyphenols on bacterial biofilm formation and quorum-sensing.
AB  - Many bacteria utilize sophisticated regulatory systems to ensure that some
      functions are only expressed when a particular population density has been
      reached. The term 'quorum-sensing' has been coined to describe this form of
      density-dependent gene regulation which relies on the production and perception
      of small signal molecules by bacterial cells. As in many pathogenic bacteria the
      production of virulence factors is quorum-sensing regulated, it has been
      suggested that this form of gene regulation allows the bacteria to remain
      invisible to the defence systems of the host until the population is sufficiently
      large to successfully establish the infection. Here we present first evidence
      that polyphenolic compounds can interfere with bacterial quorum-sensing. Since
      polyphenols are widely distributed in the plant kingdom, they may be important
      for promoting plant fitness.

PMID- 14713170
TI  - The anticancer drug cytarabine does not interact with the human erythrocyte
      membrane.
AB  - Cytarabine, an analog of deoxycytidine, is an important agent in the treatment of
      ovarian carcinoma, acute myeloid and lymphoblastic leukemia. Its mechanism of
      action has been attributed to an interference with DNA replication. The plasma
      membrane has received increasing attention as a possible target of antitumor
      drugs, where the drugs may act as growth factor antagonists and receptor
      blockers, interfere with mitogenic signal transduction or exert direct cytotoxic
      effects. Furthermore, it has been reported that drugs that exert their
      antiproliferative effect by interacting with DNA generally cause structural and
      functional membrane alterations which may be essential for growth inhibition by
      these agents. This paper describes the studies undertaken to determine the
      structural effects induced by cytarabine to cell membranes. The results showed
      that cytarabine, at a concentration about one thousand times higher than that
      found in plasma when it is therapeutically administered, did not induce
      significant structural perturbation in any of these systems. Therefore, it can be
      unambiguously concluded that this widely used anticancer drug does not interact
      at all with erythrocyte membranes.

PMID- 14713171
TI  - A potent insect chitinase inhibitor of fungal origin.
AB  - A water-soluble polysaccharide was isolated from the culture filtrate of a fungal
      strain, Sphaeropsis sp. TNPT116-Cz, as a novel insect chitinase inhibitor. It was
      purified to chromatographic homogeneity by ethanol precipitation, anion-exchange
      and gel filtration chromatography. Its molecular weight was estimated to be 16
      kDa by gel filtration HPLC. Monosaccharide analysis showed that it contained
      glucose, galactose, N-acetylglucosamine and a deoxysugar. This polysaccharide
      showed potent and specific inhibitory activity against Spodoptera litura
      chitinase with an IC50 value of 28 nM.

PMID- 14713172
TI  - RDNA methylation in Hypericum perforatum diploids and tetraploids.
AB  - The effect of the gene dosage on the expression of rRNAs was studied in Hypericum
      perforatum. The methylation levels of rDNA were analysed using the isoschizomers
      MspI and HpaII and eleven additional methylation-sensitive enzymes. No
      differences in rDNA methylation were observed between diploids and tetraploids at
      an early ontogenetic stage.

PMID- 14713173
TI  - Social class and mortality: on the importance of nutrition.

PMID- 14713174
TI  - Relationship with plasma neurohormones and dyssynchrony detected by Doppler
      echocardiography in patients undergoing permanent pacemaker implantation.
AB  - OBJECTIVE: To determine whether isovolumic relaxation flow (IRF) and isovolumic
      contraction flow (ICF) resulted from asynchrony and asynergy due to VVI and DDD
      pacemakers modulated neurohormones, we measured neurohormone levels in plasma and
      investigated the characteristics of IRF and ICF using Doppler echocardiography.
      METHODS AND RESULTS: We studied 11 patients with dual-chamber pacemakers (DDD)
      and 11 patients, with ventricular inhibiting mode (VVI). All patients underwent
      Doppler echocardiography of the left ventricle. Atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP), renin and aldosteron were measured. The LV was
      scanned for the presence of intracavitary flow during the isovolumic relaxation
      and isovolumic contraction period. The plasma levels of BNP and ANP were
      significantly lower in DDD mode than in VVI mode (56 +/- 32 pg/ml vs. 94 +/- 32
      pg/ml, p = 0.022 and 98 +/- 20 pg/ml vs. 134 +/- 17 pg/ml, p = 0.042,
      respectively). There were no significant differences in the plasma level of renin
      or aldosteron. VVI mode versus DDD mode increased isovolumic relaxation flow time
      (129 +/- 41 vs. 111 +/- 36 sec, p = 0.020) and isovolumic relaxation flow
      velocity (50 +/- 4 vs. 37 +/- 2 cm/s, p = 0.018). A strong relationship between
      blood ANP and BNP levels and IRF velocity was found in patients with a VVI
      pacemaker (r: 0.632, p: 0.028; r: 0.528, p: 0.024, respectively). CONCLUSION: VVI
      mode has a longer isovolumic relaxation time, isovolumic relaxation flow velocity
      and has higher ANP and BNP plasma levels than DDD mode. IRF resulting from
      asynergy and asynchrony in VVI mode pacemakers versus DDD mode pacemakers affects
      the plasma levels of ANP and BNP compared to renin and aldosteron.

PMID- 14713175
TI  - Aortic stiffness in patients with cardiac syndrome X.
AB  - AIM: Recently, the close relationship between aortic stiffness and cardiovascular
      mortality has aroused the interest of investigators in carrying out studies
      related to aortic stiffness. This study aims to investigate the aortic stiffness
      parameters in patients with cardiac syndrome X, a disorder that is believed to be
      a generalized disturbance of the vasodilator function of small arteries. MATERIAL
      AND METHODS: 18 patients with typical chest pain and angiographically normal
      coronary arteries associated with a positive exercise test were included in the
      study. The control group consisted of 27 patients with angiographically normal
      coronary arteries and no ischaemia on exercise testing. Antianginal medication
      was withheld 4 weeks before the study and transthoracic echocardiography was
      performed using a Hewlett-Packard Sonos 1500 instrument with a 2.5 MHz phased
      array transducer. Ascending aorta diameters were measured on the M-mode tracing
      at a level 3 cm above the aortic valve. Diameter change, pulse pressure, aortic
      strain and distensibility were measured as aortic stiffness parameters. RESULTS:
      The aortic diameter change was less in the syndrome X group than in the control
      group (0.15 +/- 0.04 cm/m2 vs. 0.28 +/- 0.12 cm/m2, p < 0.001). Likewise, aortic
      strain (9 +/- 3% vs. 18 +/- 8%, p < 0.001) and distensibility (4.01 +/- 1.71 cm2
      x dyn(-1) x 10(-3) vs. 9.95 +/- 5.08 cm2 x dyn(-1) x 10(-3), p < 0.001) was
      significantly lower in the syndrome X group than in the control group.
      CONCLUSION: The deterioration in aortic elasticity properties in patients with
      cardiac syndrome X suggests that this disease may be a more generalized
      disturbance of the vasculature.

PMID- 14713176
TI  - Lowering of furosemide dosage after clinical stabilization in patients with
      congestive heart failure.
AB  - OBJECTIVES: This study was performed to examine the safety of reducing the long
      term doses of furosemide administered to patients with congestive heart failure
      (CHF) stabilized on a standard medical treatment. METHODS AND RESULTS: Twenty
      nine patients with advanced CHF were treated with enalapril, digoxin, nitrates,
      and furosemide, as needed to alleviate their symptoms, and remained clinically
      stable for at least 3 months on those doses. Subsequently, the daily dose of
      furosemide was reduced to 1/3 of the previous dose, while the concomitant therapy
      was unchanged. All patients underwent a thorough clinical evaluation and right
      heart catheterization before and 2 months after the furosemide dose reduction.
      After the treatment optimization the NYHA functional class decreased from 2.3 +/-
      0.6 to 1.4 +/- 0.6 (p = 0.000), and the left ventricular ejection fraction
      increased from 22 +/- 10% to 32 +/- 13%, (p = 0.000). Clinical and haemodynamic
      evaluation before and after 2 months of treatment with lower furosemide doses
      showed that 24 of the 29 patients (83%) remained in a stable NYHA functional
      class and maintained a stable haemodynamic status. In the remaining 5 patients
      (17%), mean NYHA functional class increased from 1.8 +/- 0.4 to 2.4 +/- 0.6 (p =
      0.07), accompanied by a significant increase of the right and left ventricular
      filling pressures from 4.2 +/- 2.7 to 9.0 +/- 3.0 mm Hg, p = 0.018 and from 8.6
      +/- 3.0 to 19.8 +/- 3.6 mm Hg, p = 0.017, respectively. These 5 patients returned
      to a stable clinical status upon resumption of the prior doses of furosemide.
      CONCLUSIONS: Most patients with chronic CHF who were clinically stabilized on
      high doses of furosemide remained stable on a maintenance dose equal to one-third
      of the dose needed for their stabilization. Patients unable to tolerate the dose
      reduction regained their previous clinical status following the resumption of the
      prior diuretic doses.

PMID- 14713177
TI  - Modulation of the positive inotropic effect of pyruvate by energetic substrate
      availability.
AB  - Dependence of pyruvate's positive inotropic effect on energetic substrate
      availability and potential role of its mitochondrial uptake were investigated.
      Pyruvate (3, 10 and 15 mM) was added to rabbit right ventricular papillary
      muscles (protocol I; n = 10) and human right auricular trabeculae (protocol II; n
      = 6), using glucose as energetic substrate. In protocols III & IV (rabbit
      papillary muscles; n = 8 and n = 10, respectively) pyruvate's mitochondrial
      uptake was inhibited by alpha-cyano-4-hydroxycinnamate (0.5 mM) with octanoate as
      energetic substrate at 5 and 0.2 mM, respectively. In 8 additional rabbit
      papillary muscles, effects of L-alanine (10, 20 and 50 mM) were tested. In
      protocols I&II, pyruvate had a dose-dependent positive inotropic effect that was
      maximal at 10 mM, increasing in rabbit myocardium: 45.0+/-9.4% active tension,
      20.5+/-7.4% peak rate of tension rise, 32.5+/-8.6% peak isotonic shortening,
      31.2+/-11.7% peak rate of lengthening, 27.8+/-3.2% twitch duration. In protocol
      III (5 mM octanoate), pyruvate's positive inotropic effect was still present and
      even enhanced, while in protocol IV (0.2 mM octanoate) it was decreased and not
      observed with 3 mM of pyruvate. We conclude that, in rabbit papillary muscles,
      the positive inotropic effect of pyruvate is modulated by the availability of
      metabolic substrates and presumably does not depend on its mitochondrial uptake.

PMID- 14713179
TI  - Immediate sheath removal after PCI using a Femostop is feasible and safe. Results
      of a registry.
AB  - BACKGROUND: Due to antithrombotic therapy before, during, and after percutaneous
      coronary intervention (PCI), and due sometimes to the need for an urgent
      reintervention, the arterial femoral sheath is generally not removed immediately
      after PCI, unless a vascular closing device is used. This strategy causes
      discomfort to the patient, increases the workload for the nursing staff, and
      bears a risk of local complications. OBJECTIVE: The purpose of this registry is
      to demonstrate that immediate sheath removal after PCI is safe and feasible with
      the ultimate goal of enhancing patient care and hospital efficiency. METHODS: In
      patients undergoing PCI, the femoral arterial sheath was removed immediately
      after PCI in the cath lab, using a Femostop, without manual compression. The
      patient's discomfort and the complication rate were measured. The overall time
      given to haemostasis was assessed. RESULTS: A total of 339 patients were
      included. Patient discomfort during Femostop placement was assessed as follows:
      85% suffered none, 2% slight, 3% moderate, and 10% severe discomfort.
      Complication rates were: 36% ecchimosis, 10% haematoma < 6 cm, 5% haematoma > or
      = 6 cm (literature data of manual compression--LDMC--5.1% to 9%), 1%
      pseudoaneurysm (LDMC 1% to 1.8%), 0.6% need for transfusion (LDMC 2.5%), 0.3%
      need for vascular repair (LDMC 1.5% to 2.7%). The patient's immobilisation time
      after PCI was reduced from at least 10 hours to 6 hours. The time given to
      haemostasis was also reduced. CONCLUSION: Immediate sheath removal using a
      Femostop is feasible, safe, and improves the patient's comfort. The complication
      rate is equal or even lower to that reported after classical manual compression.
      Early ambulation improves the patient's comfort, and reduced time given to
      haemostasis causes organisational benefit. If a vascular closing device is not
      routinely used after PCI (for example, for economical reasons), immediate sheath
      removal after PCI could be the routine strategy.

PMID- 14713178
TI  - Dobutamine-induced ST-segment elevation associated with a biphasic response of
      wall motion in patients with a recent myocardial infarction is caused by
      myocardial ischaemia and is abolished by revascularization of the infarct-related
      artery.
AB  - OBJECTIVE: ST-segment elevation is frequently induced by dobutamine in patients
      with a recent myocardial infarction and may represent dyskinesia of the infarcted
      region or myocardial viability and ischaemia. Revascularization of the infarct
      related artery may abolish myocardial ischaemia, and thus represents a useful
      tool to verify the significance of this finding. The aim of this study was to
      assess the relation between ST-segment elevation and wall motion response during
      dobutamine echo stress test and to evaluate the effect of coronary
      revascularization with percutaneous coronary angioplasty of the infarct-related
      artery on stress test results. METHODS AND RESULTS: Twenty-two patients (17 men;
      mean age 58+/-12 years) with a first acute myocardial infarction (5 anterior
      (23%) and 17 (77%) inferior) who showed ST-segment elevation during a dobutamine
      echo stress test performed early (7+/-5 days) after the acute event where
      included in the analysis. All patients underwent coronary arteriography followed
      by percutaneous revascularization with coronary angioplasty or atherectomy with
      or without stenting of the culprit lesion and a second dobutamine echo stress
      test at a mean of 40+/-20 days after revascularization. The minimal lumen
      diameter increased from 0.63+/-0.36 to 3+/-0.44 mm and % diameter stenosis
      decreased from 80+/-11 to 12+/-7 after revascularization. At baseline evaluation
      there were 62 normal moving segments (34%), 57 (32%) akinetic and 62 (34%)
      hypokinetic segments within the area at risk. Maximal ST-segment shift changed
      from a basal mean value of 0.41+/-0.6 to a peak value of 2.15+/-0.9 mm; angina
      developed in 6/22 patients (22%). A biphasic response to dobutamine indicative of
      myocardial ischaemia within the infarcted area was observed in 20/22 patients
      (91%) and in 54/74 (73%) segments showing wall motion abnormalities. After
      revascularization of the infarct-related artery 78 (43%) segments were considered
      to be normal, 46 (25%) akinetic and 57 (32%) hypokinetic. Dobutamine-induced ST
      segment elevation in 6/22 cases (27%), but the amount of ST-segment shift at peak
      stress was significantly reduced (from 2.15+/-0.9 to 0.30+/-0.5 mm) and angina
      was present in 1 patient only (5%) despite a significant increase of double
      product compared to the pre-revascularization test (from 17,348+/-3536 to
      21,005+/-4105, p < 0.003). At echocardiographic analysis, ischaemia involved only
      4 segments (2%), 3 of them showing the persistence of a biphasic response to
      dobutamine. CONCLUSIONS: In patients with a recent myocardial infarction and no
      baseline dyskinesia dobutamine-induced ST-segment elevation in the infarct
      related leads is usually associated with a biphasic response of wall motion
      within the infarcted region and may be considered an ancillary sign of myocardial
      ischaemia because it is abolished in the great majority of cases by successful
      revascularization of the infarct-related artery.

PMID- 14713180
TI  - Left atrial function as a predictor of haemodynamic response in patients with
      mitral stenosis: a dobutamine stress echocardiographic study.
AB  - OBJECTIVE: The mechanisms of the different haemodynamic and clinical responses to
      dobutamine infusion in mitral stenosis (MS) are not clearly established. The aim
      of this study was to evaluate the relation between left atrial (LA) function and
      haemodynamic response in patients with MS during dobutamine infusion. METHODS AND
      RESULTS: Forty-two consecutive moderately symptomatic patients (33 women, 9 men;
      mean age 46+/-9, range from 26 to 66), New York Heart Association (NYHA) class II
      with MS (mean mitral valve area 1.7+/-0.1 cm2) were evaluated with dobutamine
      stress echocardiography. Haemodynamic measurements were obtained at rest and
      during peak dobutamine infusion. LA fractional shortening at rest was used as an
      index of global LA function. Group I consisting of patients with significantly
      elevated pulmonary artery pressure (> 60 mm Hg) and mean transmitral gradient (>
      15 mm Hg) at peak dobutamine infusion were defined as haemodynamically serious
      MS. Group II consisted of the remaining 30 patients whose haemodynamic data were
      below these levels. While baseline haemodynamic parameters and mitral valve
      characteristics were not different between the two groups, LA fractional
      shortening was significantly lower (18.9+/-2.8 vs. 32.3+/-5.1%, p<0.0001) and
      left atrial dimension was significantly larger in group I (49.7+/-2.3 mm vs
      43.6+/-5.3 mm, p<0.0001). Left atrial fractional shortening was negatively
      correlated with the increase in mean transmitral gradient (r:-0.58, p<0.01). When
      the patients were divided using a LA fractional shortening level of 25% as the
      cut-off point, we observed that the patients with low LA fractional shortening
      had a greater increase in mean transmitral gradient (7.3+/-3.1 mm Hg vs. 4.6+/
      1.4 mm Hg), p = 0.005) and pulmonary artery pressure (22.4+/-3.5 mm Hg vs. 16.1+/
      8.5 mm Hg, p = 0.001) compared to the patients with high LA fractional
      shortening. Based on these haemodynamic results, management was changed in 12
      patients (28%): 5 underwent percutaneous mitral balloon commissurotomy and 7
      received intensive medical treatment. CONCLUSIONS: The present study demonstrates
      that haemodynamic response during dobutamine stress echocardiography correlates
      with LA fractional shortening in patients with MS. The evaluation of left atrial
      function at rest in patients with ambiguous symptoms and mild mitral stenosis may
      be useful in clinical decision making. Atrial dysfunction at rest may predict the
      haemodynamic response during stress echo in these patients.

PMID- 14713181
TI  - Subjective symptoms and well-being 30 months after acute chest pain in a county
      hospital and a city university hospital in Sweden.
AB  - AIM: To compare various health-related aspects of quality of life during long
      term follow-up after admission to hospital due to acute chest pain in a city
      university hospital and a county hospital. METHODS: This was a retrospective
      survey of all chest pain patients > or = 30 years of age at the Sahlgrenska
      University Hospital, Goteborg, covering an area with 706 inhabitants per km2 and
      at Uddevalla County Hospital, Uddevalla, covering an area with 34 inhabitants per
      km2 over a period of six months. After 30 months all patients alive were
      approached with a questionnaire in which they were asked about various aspects of
      health-related quality of life and use of medication. RESULTS: In all, 1,813
      patients in the city hospital and 804 patients in the county hospital took part
      in the survey. The mortality and the overall proportion of patients requiring
      rehospitalization was similar in the two cohorts. Thirty months after onset of
      symptoms there was a difference between the two study populations. Patients in
      the county hospital smoked less frequently (p = 0.004). They tended to have less
      problems with chest pain at rest (p < 0.05) and dyspnoea at slight physical
      exercise (p = 0.01). Furthermore, they had less emotional symptoms (p = 0.003)
      and their state of health caused fewer problems when doing housekeeping (p =
      0.008). Differences with regard to emotional symptoms and problems when doing
      housekeeping were particularly observed among women, whereas smoking habits
      differed only among men. CONCLUSION: When comparing patients admitted to hospital
      with acute chest pain in a city university hospital and a county hospital after
      30 months some differences appeared. Patients in the county hospital appeared to
      suffer from less symptoms than patients in the city hospital. This was
      particularly observed among women. The mechanisms behind these observations are
      not clear.

PMID- 14713182
TI  - Acetylcysteine, coronary procedure and prevention of contrast-induced worsening
      of renal function: which benefit for which patient?
AB  - OBJECTIVES: This study was designed to determine whether acetylcysteine could
      provide a protective effect on renal function in a population of patients with
      normal renal function or mild to moderate chronic renal failure, usually referred
      for a coronary procedure. BACKGROUND: Contrast-induced nephropathy is a well
      recognized complication of coronary angiography. Recent studies suggest that
      saline hydration and acetylcysteine reduce the incidence of contrast-induced
      worsening of renal function in patients with pre-existing chronic renal failure
      who are undergoing computed tomography examinations. METHODS: One hundred eight
      patients were blindly and randomly assigned to receive either acetylcysteine or
      placebo before and after administration of contrast agent in association with a
      moderate hydration protocol. Serum creatinine and urea nitrogen were measured
      before and 24 hours after coronary procedure. RESULTS: The mean serum creatinine
      concentration remained unchanged 24 hours after contrast agent administration in
      both groups: from 1.04 +/- 0.26 to 1.03 +/- 0.29 mg/dl in the acetylcysteine
      group and from 1.16 +/- 1.1 to 1.06 +/- 0.41 mg/dl in the control group (p =
      0.29, for the comparison between two groups, NS). We divided the population into
      3 subgroups according to their creatinine clearance: no significant change of
      serum creatinine concentration was observed in patients with normal renal
      function nor in patients with pre-existing mild to moderate chronic renal failure
      in both groups. There was no significant difference for the incidence of contrast
      induced nephropathy between both groups (2 of the 53 patients in the
      acetylcysteine group and 3 of the 51 patients in the placebo group, p = 0.98,
      NS). CONCLUSIONS: Our data do not support the systematic use of acetylcysteine
      before a coronary procedure in patients with normal renal function or mild to
      moderate chronic renal failure, to prevent contrast-induced nephropathy.

PMID- 14713183
TI  - Colchicine-induced rhabdomyolysis in a patient with chronic heart failure.
AB  - Gout is a common co-morbidity in patients with chronic heart failure and its
      treatment is complex. We report the case of a 58-year-old man with chronic severe
      heart failure who developed rhabdomyolisis after short-term intake of colchicine.
      Although colchicine is a highly effective therapy for acute gouty arthritis, the
      dosage should be carefully titrated in patients with chronic heart failure,
      especially if renal or liver disease are also present.

PMID- 14713184
TI  - Growth of hepatocellular carcinoma into the right atrium. A case of antemortem
      diagnosis with magnetic resonance imaging of the heart.
AB  - We report the unusual case of a 54-year-old man with a right atrial mass
      (detected by two-dimensional echocardiography) associated with hepatocellular
      carcinoma. The cardiac mass, following magnetic resonance imaging of the heart,
      was proved to be due to a direct extension of the liver tumour, via the inferior
      vena cava, up to the right atrial cavity. We wish to stress that the availability
      of magnetic resonance imaging renders possible the antemortem diagnosis of
      cardiac metastasis due to malignant tumours.

PMID- 14713185
TI  - Lacrimo-auriculo-dento-digital syndrome with QT prolongation.
AB  - We present a case of a young boy in whom lacrimo-auriculo-dental-digital (LADD)
      syndrome with QT prolongation was detected. According to Bazett's formula,
      corrected QT was 504 ms. There were no published data about LADD syndrome with QT
      prolongation. This is the first case concerning LADD syndrome associated with QT
      prolongation. It is known that deafness and QT prolongation occur in potassium
      channel dysfunction. QT prolongation and deafness may be associated with
      potassium channel dysfunction in patients with LADD syndrome. As a result QT
      prolongation may be a new component of the LADD syndrome.

PMID- 14713186
TI  - Early ischaemic preconditioning reduces spinal cord injury in transient
      ischaemia.

PMID- 14713187
TI  - A mandibular protruding device in obstructive sleep apnea and snoring.
AB  - The overall purpose behind treatment in sleep-breathing disorders is to ease
      breathing and thereby reduce the risk of morbidity. The mandibular protruding
      device (MPD) is one method of treating both obstructive sleep apnea (OSA) and
      snoring. The aims of the studies were to study MPD users after 2 years and
      evaluate the following aspects of the MPD: subjective and objective effects on
      sleep, influences on airway passages and hard tissues, and the incidence and
      types of adverse events of the masticatory system including temporomandibular
      disorders. Further aims were to evaluate the impact of body posture and the
      effects of the MPD on pharyngeal width and to validate two methods for measuring
      mandibular protrusion and MPD advancement. MATERIALS AND METHODS: Seventy-seven
      subjects with OSA or snorers without OSA. were admitted to the study after a
      medical examination, which included a somnographic registration. The patients
      completed questionnaires regarding sleep quality and symptoms from the
      masticatory system, and underwent a clinical jaw function examination, were given
      an MPD, and were subjected to lateral cephalometric examination. Two follow-ups,
      6 months and 2 years after MPD treatment were conducted. The study population
      comprised 65 patients at the 2-year follow-up. RESULTS: At the 2-year follow-up,
      a significant reduction of the subjective complaints was noted by 90% of the MPD
      users. In the objective evaluation, the oxygen desaturation index (ODI) of the
      OSA group (n = 39) decreased significantly from a mean of 14.7 to 3.1 and the
      mean arterial oxygen saturation (SaO2) increased significantly from 78% to 89%.
      The snorers maintained their initial values. In the total group, MPD treatment
      significantly increased most pharyngeal measures and lifted the hyoid bone. The
      pharyngeal area decreased significantly--by more than 50%--when the patient was
      supine, and the velum area increased significantly. At the 2-year follow-up, on
      upright cephalogram without MPD, the pharyngeal area had significantly increased
      and the velum area had significantly decreased. The mandible was posteriorly
      rotated (P < 0.01) as well as the lower incisors were proclined (P < 0.05).
      Mandibular advancement and vertical opening with an MPD, as measured with a
      ruler, compared well with measurements taken from a cephalogram. At the 2-year
      follow-up significant changes in the mean mandibular range of protrusion (+0.6
      mm), overjet (-0.5 mm), and overbite (-0.8 mm) were registered. Nine of the 65
      patients had developed a lateral open bite, and 2 were aware of the change. The
      reported frequency of headache was significantly reduced. At the 2-year follow-up
      there was a significant reduction in pain during mandibular movements.
      CONCLUSIONS: MPD treatment significantly reduced subjective complaints of sleep
      disturbances and significantly reduced ODI values among OSA patients. A high MPD
      compliance rate after 2 years (84%) indicated a well-tolerated treatment and a
      low rate of side effects were noted. The key factor in OSA and snoring is the
      obstruction of pharynx. The MPD treatment significantly increased the pharyngeal
      passages and significantly reduced the size of velum and thereby facilitated the
      breathing.

PMID- 14713188
TI  - Modeling of enzyme-substrate complexes for the metalloproteases MMP-3, ADAM-9 and
      ADAM-10.
AB  - The matrix metalloproteases (MMPs) and the ADAMs (A Disintegrin And
      Metalloprotease domain) are proteolytic enzyme families containing a catalytic
      zinc ion, that are implicated in a variety of normal and pathological processes
      involving tissue remodeling and cancer. Synthetic MMP inhibitors have been
      designed for applications in pathological situations. However, a greater
      understanding of substrate binding and the catalytic mechanism is required so
      that more effective and selective inhibitors may be developed for both
      experimental and clinical purposes. By modeling a natural substrate spanning P4
      P4' in complex with the catalytic domains, we aim to compare substrate
      specificities between Stromelysin-1 (MMP-3), ADAM-9 and ADAM-10, with the aid of
      molecular dynamics simulations. Our results show that the substrate retains a
      favourable antiparallel beta-sheet conformation on the P-side in addition to the
      well-known orientation of the P'-region of the scissile bond, and that the
      primary substrate selectivity is dominated by the sidechains in the S1' pocket
      and the S2/S3 region. ADAM-9 has a hydrophobic residue as the central determinant
      in the S1' pocket, while ADAM-10 has an amphiphilic residue, which suggests a
      different primary specificity. The S2/S3 pocket is largely hydrophobic in all
      three enzymes. Inspired by our molecular dynamics calculations and supported by a
      large body of literature, we propose a novel, hypothetical, catalytic mechanism
      where the Zn-ion polarizes the oxygens from the catalytic glutamate to form a
      nucleophile, leading to a tetrahedral oxyanion anhydride transition state.

PMID- 14713189
TI  - Inhibition and substrate recognition--a computational approach applied to HIV
      protease.
AB  - We have developed a computational approach in which an inhibitor's strength is
      determined from its interaction energy with a limited set of amino acid residues
      of the inhibited protein. We applied this method to HIV protease. The method uses
      a consensus structure built from X-ray crystallographic data. All inhibitors are
      docked into the consensus structure. Given that not every ligand-protein
      interaction causes inhibition, we implemented a genetic algorithm to determine
      the relevant set of residues. The algorithm optimizes the q2 between the sum of
      interaction energies and the observed inhibition constants. The best possible
      predictive model resulting has a q2 of 0.63. External validation by examining the
      predictivity for compounds not used in derivation of the model leads to a
      prediction accuracy between 0.9 and 1.5 log10 unit. Out of 198 residues in the
      whole protein, the best internally predictive model defines a subset of 20
      residues and the best externally predictive model one of 9 residues. These
      residues are distributed over the subsites of the enzyme. This approach provides
      insight in which interactions are important for inhibiting HIV protease and it
      allows for quantitative prediction of inhibitor strength.

PMID- 14713190
TI  - Computational studies of new potential antimalarial compounds--stereoelectronic
      complementarity with the receptor.
AB  - One of the most important pharmacological mechanisms of antimalarial action is
      the inhibition of the aggregation of hematin into hemozoin. We present a group of
      new potential antimalarial molecules for which we have performed a DFT study of
      their stereoelectronic properties. Additionally, the same calculations were
      carried out for the two putative drug receptors involved in the referred
      activity, i.e., hematin mu-oxo dimer and hemozoin. A complementarity between the
      structural and electronic profiles of the planned molecules and the receptors can
      be observed. A docking study of the new compounds in relation to the two putative
      receptors is also presented, providing a correlation with the defined
      electrostatic complementarity.

PMID- 14713191
TI  - A novel scoring function for molecular docking.
AB  - We present a novel scoring function for docking of small molecules to protein
      binding sites. The scoring function is based on a combination of two main
      approaches used in the field, the empirical and knowledge-based approaches. To
      calibrate the scoring function we used an iterative procedure in which a ligand's
      position and its score were determined self-consistently at each iteration. The
      scoring function demonstrated superiority in prediction of ligand positions in
      docking tests against the commonly used Dock, FlexX and Gold docking programs. It
      also demonstrated good accuracy of binding affinity prediction for the docked
      ligands.

PMID- 14713192
TI  - New atom-type-based AI topological indices: application to QSPR studies of
      aldehydes and ketones.
AB  - Multiple linear regression (MLR) analysis based on a combined use of the modified
      Xu index and the atom-type based AI indices is performed to construct
      quantitative structure-property models on several data sets of organic compounds
      including aliphatic aldehydes and/or ketones. For each of the physical properties
      (the normal boiling points, molar refractions, gas heat capacities at 25 degrees
      C, water solubility at 25 degrees C, and n-octanol/water partition coefficient at
      25 degrees C), high quality QSPR models are obtained, particularly the decrease
      in the standard error is within the range of 23.6-75.9% relative to the linear
      models with the modified Xu index alone. For individual subsets containing only
      aldehydes or ketones, in the majority of cases the quality of the model can be
      further improved. The significant improvement verifies the efficiency of the
      present approach and also indicates the usefulness of these indices for
      application to a wide range of physical properties. The results indicate that the
      physical properties studied are dominated by molecular size but atom types have
      smaller influences, especially the oxygen atom seems to be most important due to
      intermolecular polar interactions. The final models are validated to be
      statistically reliable using the leave-one-out cross-validation and/or an
      external test set.

PMID- 14713193
TI  - Safety, risk and the precautionary principle: rethinking precautionary approaches
      to the regulation of transgenic plants.
AB  - Operationalizing the Cartagena Protocol on Biosafety will require resolving
      disputes about the meaning of the term 'precautionary approach' in the treaty
      text. Although the terms precautionary approach and precautionary principle have
      been referred to in the regulation of transgenic plants for nearly a decade, no
      customary expectation of what actions either requires has developed. If specific
      obligations for regulators, regulated entities, or both are not established,
      compliance will be impossible. This essay examines various interpretations of the
      precautionary principle, discusses their shortcomings, and suggests a way to
      rethink the regulation of transgenic plants that focuses on genuine uncertainty.
      Transgenic plants with familiar phenotypes should be subject to considerably less
      regulatory scrutiny than those whose risks are genuinely unknown, or known to
      pose heightened risk.

PMID- 14713194
TI  - Concerted action of endogenous and heterologous phytase on phytic acid
      degradation in seed of transgenic wheat (Triticum aestivum L.).
AB  - Expression of heterologous phytases in crops offers a great potential for
      improving phosphate and mineral bioavailability in food and feed. In this context
      it is of relevance to describe the concerted action of endogenous and hetrologous
      phytases on the transgenic seed inositol phosphate profile. Here we report metal
      dye detection HPLC analysis of inositol phosphate degradation in flour from
      transgenic wheat materials possessing wheat endogenous 6-phytase [EC 3.1.3.26]
      and Aspergillus 3-phytase [EC 3.1.3.8] activities under the control of the maize
      ubiquitin-1 promoter and the wheat high molecular weight glutenin subunit 1DX5
      promoter respectively. During 50 min incubation there is an accumulation of InsP5
      to InsP2 breakdown products in non-transgenic material. Aspergillus niger phytase
      specific breakdown products are transiently detected in transgenic material but
      after 50 min incubation virtually all InsP5, InsP4 and InsP3 isomers are
      hydrolysed.

PMID- 14713196
TI  - Transgenic tobacco and apple plants expressing biotin-binding proteins are
      resistant to two cosmopolitan insect pests, potato tuber moth and lightbrown
      apple moth, respectively.
AB  - Tobacco (Nicotiana tabacum cv. Samsun) and apple (Malus x domestica cv. Royal
      Gala) plants expressing avidin or strepavidin were produced using Agrobacterium
      tumefaciens-mediated transformation. ELISA assays showed that avidin expression
      ranged from 3.1 to 4.6 microM in tobacco and from 1.9 to 11.2 microM in apple and
      streptavidin expression ranged from 11.4 to 24.5 microM in tobacco and from 0.4
      to 14.6 microM in apple. Expressed at these levels, both biotin-binding proteins
      conferred a high level of insect resistance on transformed tobacco plants to
      larval potato tuber moth (PTM), Phthorimaea operculella (Zeller) (fam.
      Gelechiidae) and on apple plants to larvae of the lightbrown apple moth (LBAM)
      Epiphyas postvittana (Walker) (fam. Tortricidae). More than 90% of PTM larvae
      died on tobacco plants expressing either avidin or streptavidin genes within 9
      days of inoculation. Mortality of LBAM larvae was significantly higher (P < 0.05)
      on three avidin-expressing (89.6, 84.9 and 80.1%) and two streptavidin-expressing
      (90 and 82.5%) apple plant lines than on non-transformed control plants (14.1%)
      after 21 days. Weight of LBAM larvae was also significantly reduced by feeding on
      all apple shoots expressing avidin and on apple shoots expressing streptavidin at
      levels of 3.8 microM and above.

PMID- 14713195
TI  - Mono-allelic expression of variegating transgene locus in the mouse.
AB  - We have generated transgenic mice which express an ovine beta-lactoglobulin
      transgene during lactation. In two transgenic lines, BLG/7 and BLG/45, beta
      lactoglobulin protein levels vary between siblings, reflected at the cellular
      level by a mosaic transgene expression pattern in the mammary tissue that is
      reminiscent of position effect variegation. To investigate whether this
      variegating expression profile can be affected by the introduction of an
      identical variegating locus on the homologous chromosome, we compared the beta
      lactoglobulin expression profiles in mice hemizygous or homozygous for the
      transgene locus. In BLG/45 mice, milk protein analysis revealed that transgene
      expression was effectively doubled in homozygous compared to hemizygous mice. In
      contrast, beta-lactoglobulin protein in hemizygous and homozygous BLG/7 mice
      displayed a similar range; although minimum expression levels were doubled in the
      homozygous population, the maximum level of expression was indistinguishable
      between the two populations. Fluorescent in situ hybridisation (FISH) for
      transgene mRNA indicated that for a given protein level, the extent of cellular
      expression is similar in both BLG/7 populations. In homozygous mice genomic DNA
      and nuclear RNA FISH demonstrated that only one of the two BLG/7 loci is active
      in expressing cells, while two transcription foci were present in BLG/45
      homozygous mice. This mono-allelic transgene expression pattern is not inherited
      through the germline, as hemizygous mice bred from homozygous parents expressed
      at the expected hemizygous population level. We discuss these observations in the
      context of known epigenetic events such as imprinting and trans-inactivation.

PMID- 14713197
TI  - Expression of the B subunit of E. coli heat-labile enterotoxin in the
      chloroplasts of plants and its characterization.
AB  - Transgenic chloroplasts have become attractive systems for heterologous gene
      expressions because of unique advantages. Here, we report a feasibility study for
      producing the nontoxic B subunit of Escherichia coli heat-labile enterotoxin
      (LTB) via chloroplast transformation of tobacco. Stable site-specific integration
      of the LTB gene into chloroplast genome was confirmed by PCR and genomic Southern
      blot analysis in transformed plants. Immunoblot analysis indicated that plant
      derived LTB protein was oligomeric, and dissociated after boiling. Pentameric LTB
      molecules were the dominant molecular species in LTB isolated from transgenic
      tobacco leaf tissues. The amount of LTB protein detected in transplastomic
      tobacco leaf was approximately 2.5% of the total soluble plant protein,
      approximately 250-fold higher than in plants generated via nuclear
      transformation. The GM1-ELISA binding assay indicated that chloroplast
      synthesized LTB protein bound to GM1-ganglioside receptors. LTB protein with
      biochemical properties identical to native LTB protein in the chloroplast of
      edible plants opens the way for inexpensive, safe, and effective plant-based
      edible vaccines for humans and animals.

PMID- 14713198
TI  - Heterogeneous inducible mammary-specific expression of Jab/SOCS1 in lactating
      transgenic mice is associated with no obvious phenotype, even at the cellular
      level.
AB  - The cytokine-inducible suppressor of cytokine signalling SOCS1, or JAB, has been
      shown to be implicated in vitro in the negative regulation of the prolactin
      receptor-induced activation of JAK2 and STAT5. Disruption of this gene in vivo
      resulted in an accelerated mammary gland development. In the present experiment,
      we assessed the potential impact on the lactation process of the doxycycline
      inducible mammary-controlled expression of this gene in transgenic mice. Three
      transgenic mouse lines that expressed JAB specifically in the mammary gland in a
      conditional manner following doxycycline treatment were successfully established.
      The resulting overall expression of JAB was high and ranged from half to four
      times that of the endogenously expressed homologous gene in the thymus. It was
      found to be highly heterogeneous in the mammary epithelium, with less than 5% of
      JAB-expressing cells detected. Phenotypic analysis of these transgenic mice
      exhibiting doxycycline-induced JAB expression did not reveal any obvious effect
      on the lactation process. Double immunostaining experiments suggested that JAB
      expression in vivo did not significantly affect the beta-casein gene expression
      and the STAT5a nuclear localisation. These results do not support a role for JAB
      in the disruption of the lactation process.

PMID- 14713199
TI  - Transgenic expression of the Arabidopsis DELLA proteins GAI and gai confers
      altered gibberellin response in tobacco.
AB  - Bioactive gibberellin (GA) regulates the growth and development of a wide array
      of plant species. GA exerts its effects via members of the DELLA protein family
      of putative transcriptional regulators. The GAI gene encodes GAI, a DELLA protein
      from Arabidopsis thaliana (L.) Heyhn. A mutant allele, gai, encodes a mutant
      protein (gai) that has altered properties, and confers a dominant, reduced GA
      response, dwarf phenotype. Here we describe experiments to investigate the
      effects of transgenic expression of GAI and gai in tobacco. Constructs permitting
      the expression of the GAI and gai open reading frames (ORFs) at higher (driven by
      the cauliflower mosaic virus 35S promoter) and lower (driven by the original
      Arabidopsis GAI promoter) levels in tobacco were made. We show that low-level
      expression of GAI has no detectable effect on tobacco GA-responses. In contrast,
      high-level expression of GAI clearly affects the growth of adult tobacco plants
      and the GA-responsiveness of tobacco hypocotyls. Both low- and high-level
      expression of gai have effects on tobacco GA responses. Thus, tobacco GA
      responses are affected by transgenic expression of GAI/gai, and the degree to
      which these responses are affected is related to the level of transgene
      expression.

PMID- 14713200
TI  - Transgenic tobacco expressing Pinellia ternata agglutinin confers enhanced
      resistance to aphids.
AB  - Tobacco leaf discs were transformed with a plasmid, pBIPTA, containing the
      selectable marker neomycin phosphotransferase gene (nptII) and Pinellia ternata
      agglutinin gene (pta) via Agrobacterium tumefaciens-mediated transformation.
      Thirty-two independent transgenic tobacco plants were regenerated. PCR and
      Southern blot analyses confirmed that the pta gene had integrated into the plant
      genome and northern blot analysis revealed transgene expression at various levels
      in transgenic plants. Genetic analysis confirmed Mendelian segregation of the
      transgene in T1 progeny. Insect bioassays showed that transgenic plants
      expressing PTA inhibited significantly the growth of peach potato aphid (Myzus
      persicae Sulzer). This is the first report that transgenic plants expressing pta
      confer enhanced resistance to aphids. Our study indicates that the pta gene can
      be used as a supplement to the snowdrop (Galanthus nivalis) lectin gene (gna) in
      the control of aphids, a sap-sucking insect pest causing significant yield losses
      of crops.

PMID- 14713201
TI  - The insulator effect of the 5'HS4 region from the beta-globin chicken locus on
      the rabbit WAP gene promoter activity in transgenic mice.
AB  - Previous studies have shown that the 5'HS4 DNaseI hypersensitive site of the
      chicken beta-globin locus is endowed with classic insulator activities: (i) it
      blocks the interaction between promoter and enhancers when it is inserted between
      them (ii) it confers expression of integrated foreign genes independent of their
      position in the chromatin. The aim of this present work was to determine whether
      the 5'HS4 element was able to stimulate the expression level and/or to increase
      the expression frequency of a luc+ reporter gene controlled by the rabbit WAP
      gene promoter. Two constructs with 5'HS4 insulator (p5'HS4-WAPluc) or without
      (pWAPluc) were introduced in mouse fertilised oocytes. All transgenic lines
      containing the 5'HS4 element (six lines) expressed the transgene whereas only two
      out of eight lines harbouring the pWAP-luc construct expressed the transgene to a
      significant level. Moreover, the mean level of expression was seven times higher
      in p5'HS4WAP-luc lines than in pWAP-luc lines. Even all these benefits on
      transgene expression, the 5'HS4 element did not confer a copy-dependent
      expression, did not decrease the ectopic expression of the reporter gene and did
      not decrease the variability of expression. Thus, the 5'HS4 element does not have
      all the properties of a perfect insulator on a construct containing the luc+
      reporter gene controlled by the rabbit WAP promoter.

PMID- 14713202
TI  - Predicting the spread of herbicide resistance in Australian canola fields.
AB  - A common concern expressed about the commercial release of transgenic canola into
      cropping systems is the risks of unwanted gene flow between varieties.
      Experimental data is emerging that answers some of the theoretical questions that
      have been posed when considering gene flow on a landscape scale. This study
      developed models that utilise some of this published data in an attempt to
      quantify the spread of transgenes in a commercial farming system. The models,
      which included bootstrapping the empirical data and three mathematical
      simulations, were compared with each other and the published data. One of the
      mathematical models estimated average resistance frequency by imposing a Poisson
      distribution around the published mean value for a single transgenic field
      surrounded by conventional canola fields and the other two were derived from the
      theory that pollen flow decreased with distance in the form of a log decay curve.
      The predictions of all models suggested that the average frequency of resistance
      occurring from pollen flow in neighbouring canola fields, even when multiple
      transgenic fields are adjacent to the conventional fields, are likely to be below
      the current internationally accepted thresholds for contamination.

PMID- 14713203
TI  - A simple and convenient method for preparing chimeric animals from embryonic stem
      (ES) cells.
AB  - Gene targeting in embryonic stem (ES) cells followed by preparation of chimeric
      animals is the most effective method to study the function of a gene during
      development and differentiation. Here, we describe a cost effective and
      convenient method to produce chimeric animals. Cryopreserved 8-16 cell mouse
      embryos were aggregated with ES cells in microwell petridishes (Khillan & Bao,
      1997) to obtain blastocysts. Also, freshly isolated morulas were aggregated with
      ES cells that were positive for the green florescent protein (GFP). After
      overnight culture, the blastocysts that exhibited GFP florescence were
      transferred to the pseudo-pregnant mothers to obtain chimeric animals. The
      animals displayed high degree of ES contribution and transmitted gene to their
      progeny after mating with the normal animals. The studies demonstrate that the
      aggregation with cryopreserved embryos followed by the pre-selection for a visual
      marker can be a high throughput and cost effective method to create chimeric
      animals from the gene targeted ES cells.

PMID- 14713204
TI  - Utility of a C57BL/6 ES line versus 129 ES lines for targeted mutations in mice.
AB  - Inbred ES lines, though useful for generating targeted mutations in mice, are
      used infrequently. To appreciate the relative efficiency of inbred ES lines, a
      C57BL/6 ES line was compared with 129 strain ES lines for effectiveness in
      chimera formation leading to the establishment of targeted mutations in mice.
      Data from a transgenic facility spanning 7 years were collected. C57BL/6 ES cells
      injected into Balb/c embryos results in lower coat color chimerism than do 129 ES
      cells injected into C57BL/6 embryos. Combined data indicate that five independent
      targeted C57BL/6 clones should be injected as compared to three independent 129
      clones to generate enough chimeras to effectively test for germ-line
      transmission. Thus, although less efficient than 129 ES lines, the C57BL/6 ES
      line is a relatively competent line and useful for the routine generation of
      targeted mutations in mice on a defined genetic background.

PMID- 14713205
TI  - Early parity significantly elevates mammary tumor incidence in MMTV-c-myc
      transgenic mice.
AB  - Female transgenic mice, in which a murine c-myc gene has been placed under the
      transcriptional control of the mouse mammary tumor virus long terminal repeat,
      are prone to developing mammary adenocarcinomas. Owing to the manner in which
      these mammary tumors develop, it is clear that exogenous expression of the c-myc
      transgene is necessary to but insufficient for murine mammary tumorigenesis. The
      genetic background of study mice has been shown to influence the phenotype
      induced by different transgenes; furthermore, mammary tumor initiation and
      progression induced by different transgenes has been shown to be susceptible to
      significant modification with alterations in and mixing of the genetic background
      of the study mice. We bred MMTV-c-myc transgenic mice onto a mixed genetic
      background that resulted in a very significant suppression of mammary tumor
      incidence for parous mice, bred continuously starting at 10 weeks of age. In this
      paper, we show that mammary tumor incidence is significantly elevated in these
      mixed background MMTV-c-myc transgenic mice when they are bred continuously,
      starting at 7 weeks of age. Early breeding of these mice did not influence
      mammary tumor multiplicity, latency, histopathology, or number of pregnancies at
      time of tumor development. These results are the first to demonstrate that
      breeding age influences mammary tumor incidence in MMTV-c-myc transgenic mice.
      They suggest that mammary gland susceptibility to tumorigenesis, resulting from
      the expression of c-myc, may vary with glandular development as is seen for
      chemical carcinogens.

PMID- 14713206
TI  - The potential benefits of insulators on heterologous constructs in transgenic
      animals.

PMID- 14713207
TI  - Why study regulation of genes in inherited disorders?

PMID- 14713208
TI  - Phenotypic variability (heterogeneity) of peroxisomal disorders.
AB  - Peroxisomes perform a multitude of biosynthetic and catabolic functions, many of
      which are related to lipid metabolism. Peroxisomal disorders result either from
      deficiency of a single peroxisomal enzyme or protein, or from a defect in the
      complex mechanism of peroxisomal biogenesis, resulting in deficiency of several
      or multiple peroxisomal functions. These can be assessed by a battery of
      biochemical assays, enabling a biochemical phenotype to be defined that is
      specific and diagnostic for each of the peroxisomal disorders. Some peroxisomal
      disorders have unique and specific clinical phenotypes, which may be diagnostic.
      Others share patterns of clinical abnormalities (particularly neurological
      dysfunction, craniofacial dysmorphism, skeletal defects, sensory deafness,
      retinopathy) consistent with defined clinical phenotypes, but with considerable
      overlap and heterogeneity. To a certain extent, the clinical features of a
      particular disorder reflect the accumulation or deficiency of specific
      metabolites. Thus, the same clinical phenotypes may be caused by both single
      enzyme defects and PBDs. Furthermore, the same defect may present with different
      clinical phenotypes. In general, the severity of the clinical phenotype
      correlates with the degree of biochemical dysfunction. The clinical heterogeneity
      of peroxisomal disorders constitutes a diagnostic challenge demanding a high
      index of suspicion on the clinician's part.

PMID- 14713209
TI  - Mulibrey nanism--a novel peroxisomal disorder.

PMID- 14713210
TI  - Peroxisomes during development and in distinct cell types.

PMID- 14713211
TI  - Tissue-specific expression of two peroxisomal 3-ketoacyl-CoA thiolase genes in
      wild and PPAR alpha-null mice and induction by fenofibrate.

PMID- 14713212
TI  - Clinical features & retinal function in patients with adult Refsum syndrome.

PMID- 14713213
TI  - Is there a phenotype/genotype correlation in peroxisome biogenesis disorders
      (PBDs)?

PMID- 14713214
TI  - Biochemical markers predicting survival in peroxisome biogenesis disorders.

PMID- 14713215
TI  - Identification of PEX7 as the second gene involved in Refsum disease.

PMID- 14713216
TI  - Genetic heterogeneity in Japanese patients with peroxisome biogenesis disorders
      and evidence for a founder haplotype for the most common mutation in PEX10 gene.

PMID- 14713217
TI  - Disturbances of valine metabolism in patients with peroxisomal biogenesis
      disorders.

PMID- 14713218
TI  - Mouse models and genetic modifiers in X-linked adrenoleukodystrophy.

PMID- 14713219
TI  - Evidence against the adrenoleukodystrophy-related gene acting as a modifier of X
      adrenoleukodystrophy.

PMID- 14713220
TI  - Peroxisome mosaics.

PMID- 14713221
TI  - Resolution of the molecular defect in a patient with peroxisomal mosaicism in the
      liver.

PMID- 14713222
TI  - Lessons from knockout mice. I: Phenotypes of mice with peroxisome biogenesis
      disorders.

PMID- 14713223
TI  - Lessons from knockout mice II: Mouse models for peroxisomal disorders with single
      protein deficiency.

PMID- 14713224
TI  - DNA methylation and human diseases.

PMID- 14713225
TI  - RNA silencing.

PMID- 14713226
TI  - Imprinting.

PMID- 14713227
TI  - Histone modifications--marks for gene expression?

PMID- 14713228
TI  - A paradigm for gene regulation: inflammation, NF-kappaB and PPAR.
AB  - The onset of inflammatory gene expression is driven by the transcription factor
      NF-kappaB, whose transcriptional activity is regulated at multiple levels. First,
      NF-kappaB activity is regulated by cytoplasmic degradation of the IkappaB
      inhibitor and nuclear translocation. Second, the nuclear p65 transactivation
      potential can be further influenced by posttranslational modifications, such as
      phosphorylation and/or acetylation. The p65 phosphorylation is a process highly
      regulated by both cell- and stimulus-dependent activating kinases. Ser276
      phosphorylation seems to be highly important considering its crucial role in the
      interaction with and the engagement of the cofactor CBP/p300. We have identified
      MSK1 as an acting kinase in the TNF-signalling pathway, where it is responsible
      for p65 phosphorylation at Ser276, as well as for H3 phosphorylation of Ser10 in
      IL-6 promoter-associated chromatin (Fig. 1) (Saccani et al., 2002; Vermeulen et
      al., 2002, 2003). To our knowledge, this was the first report that identifies one
      particular kinase involved in transcription factor phosphorylation and histone
      modification at the level of a single promoter in order to establish gene
      activation. The question of which element takes the initial step to recruit and
      to assemble the activated transcription complex still remains unanswered (Vanden
      Berghe et al., 2002). PPAR alpha negatively interferes with inflammatory gene
      expression by up-regulation of the cytoplasmic inhibitor molecule IkappaB alpha,
      thus establishing an autoregulatory loop (Fig. 1). This induction takes place in
      the absence of a PPRE, but requires the presence of NF-kappaB and Sp1 elements in
      the IkappaB alpha promoter sequence as well as DRIP250 cofactors. The detailed
      mechanism how PPAR can activate genes in a non-DNA-binding way needs further
      investigation; moreover, it is at present not clear whether this upregulation,
      unlike the inhibitory effect of glucocorticoids, is a cell type- or a PPAR
      specific phenomenon.

PMID- 14713229
TI  - Methods: DNA methylation.

PMID- 14713230
TI  - RNA interference in mammalian systems--a practical approach.

PMID- 14713232
TI  - Characterization of the peroxisomal cycling receptor Pex5p import pathway.

PMID- 14713233
TI  - Interaction of PEX3 and PEX19 visualized by fluorescence resonance energy
      transfer (FRET).

PMID- 14713234
TI  - Gene regulation of peroxisomal enzymes by nutrients, hormones and nuclear
      signalling factors in animal and human species.

PMID- 14713235
TI  - Regulation of peroxisomal genes by DHEA and vitamin D.

PMID- 14713236
TI  - Effect of dehydroepiandrosterone (DHEA) supplementation on fatty acid and hormone
      levels in patients with X-linked adrenoleukodystrophy.

PMID- 14713237
TI  - Dehydroepiandrosterone induction of the Abcd2 and Abcd3 genes encoding
      peroxisomal ABC transporters: implications for X-linked adrenoleukodystrophy.

PMID- 14713238
TI  - Phytanic and pristanic acid are naturally occuring ligands.

PMID- 14713239
TI  - Modified peroxisomes in primary hepatocyte cultures.

PMID- 14713240
TI  - Modifying the peroxisomes by cell & tissue culture: II. Fibroblasts.

PMID- 14713241
TI  - Peroxisomes and PPARs in cultured neural cells.

PMID- 14713242
TI  - Pharmacological induction of redundant genes for a therapy of X-ALD:
      phenylbutyrate and other compounds.

PMID- 14713243
TI  - Peroxisomal fatty acid alpha- and beta-oxidation in health and disease: new
      insights.

PMID- 14713244
TI  - Role of phytanoyl-CoA 2-hydroxylase in phytanic acid metabolism.

PMID- 14713245
TI  - Thiamine pyrophosphate: an essential cofactor in the mammalian metabolism of 3
      methyl-branched fatty acids--implications for thiamine deficiencies?

PMID- 14713246
TI  - Metabolic regulation of peroxisomal and mitochondrial fatty acid oxidation.

PMID- 14713247
TI  - Cholesterol biosynthesis and regulation: role of peroxisomes.

PMID- 14713248
TI  - Peroxisome deficiency does not result in deficiency of enzymes involved in
      cholesterol biosynthesis.

PMID- 14713249
TI  - Cholesterol regulates ABCD2 gene expression: implications for X-linked
      adrenoleukodstrophy.

PMID- 14713250
TI  - Regulation of farnesyl diphosphate synthase gene expression by fatty acids.

PMID- 14713251
TI  - Plasmalogens, docosahexaenoic acid and neurological disorders.

PMID- 14713252
TI  - Targeted disruption of ether lipid synthesis in mice.

PMID- 14713253
TI  - Evaluation of the preventive effect of glyceryl trioleate-trierucate ("Lorenzo's
      oil") therapy in X-linked adrenoleukodystrophy: results of two concurrent trials.

PMID- 14713254
TI  - The management of patients with neuroendocrine tumours.

PMID- 14713255
TI  - Highlights of the biology of endocrine tumours of the gut and pancreas.
AB  - Originating from cells of the diffuse endocrine system the endocrine tumours of
      the gut and the pancreatic tract are rare entities characterized by a common
      phenotypic aspect and producing several bioactive substances including growth
      factors. Two major categories are identified: well-differentiated and poorly
      differentiated tumours. The clinical behaviour varies ranging from benign to low
      grade malignant for well-differentiated tumours/carcinomas to high grade
      malignant for poorly differentiated carcinomas. The two major categories of well
      differentiated and poorly differentiated tumours display distinct phenotypes and
      genetic backgrounds possibly supporting distinct histogenesis. Genetic
      abnormalities associated with either induction or progression of tumours may vary
      depending on the site of origin.

PMID- 14713256
TI  - Genetics of neuroendocrine and carcinoid tumours.
AB  - Neuroendocrine tumours (NETs) originate in tissues that contain cells derived
      from the embryonic neural crest, neuroectoderm and endoderm. Thus, NETs occur at
      many sites in the body, although the majority occur within the gastro-entero
      pancreatic axis and can be subdivided into those of foregut, midgut and hindgut
      origin. Amongst these, only those of midgut origin are generally argentaffin
      positive and secrete serotonin, and hence only these should be referred to as
      carcinoid tumours. NETs may occur as part of complex familial endocrine cancer
      syndromes, such as multiple endocrine neoplasia type 1 (MEN1), although the
      majority occur as non-familial (i.e. sporadic) isolated tumours. Molecular
      genetic studies have revealed that the development of NETs may involve different
      genes, each of which may be associated with several different abnormalities that
      include point mutations, gene deletions, DNA methylation, chromosomal losses and
      chromosomal gains. Indeed, the foregut, midgut and hindgut NETs develop via
      different molecular pathways. For example, foregut NETs have frequent deletions
      and mutations of the MEN1 gene, whereas midgut NETs have losses of chromosome 18,
      11q and 16q and hindgut NETs express transforming growth factor-alpha and the
      epidermal growth factor receptor. Furthermore, in lung NETs, a loss of chromosome
      3p is the most frequent change and p53 mutations and chromosomal loss of 5q21 are
      associated with more aggressive tumours and poor survival. In addition,
      methylation frequencies of retinoic acid receptor-beta, E-cadherin and RAS
      associated domain family genes increase with the severity of lung NETs. Thus the
      development and progression of NETs is associated with specific genetic
      abnormalities that indicate the likely involvement of different molecular
      pathways.

PMID- 14713257
TI  - Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours.
AB  - Five somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4)
      and sst(5), have been cloned and characterised. The five sst subtypes all bind
      natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine
      pancreatic and endocrine digestive tract tumours also express multiple sst
      subtypes, but sst(2) predominance is generally found. However, there is
      considerable variation in sst subtype expression between the different tumour
      types and among tumours of the same type. The predominant expression of sst(2)
      receptors on pancreatic endocrine or carcinoid tumours is essential for the
      control of hormonal hypersecretion by the octapeptide somatostatin analogues such
      as octreotide and lanreotide. Somatostatin and its octapeptide analogues are also
      able to inhibit proliferation of normal and tumour cells. The high density of
      sst(2) or sst(5) on pancreatic endocrine or carcinoid tumours further allows the
      use of radiolabelled somatostatin analogues for in vivo visualisation. The
      predominant expression of sst(2) receptors in these tumours and the efficiency of
      sst(2) receptors to undergo agonist-induced internalisation is also essential for
      the application of radiolabelled octapeptide somatostatin analogues. Currently,
      [(111)In-DTPA(0)]octreotide, [(90)Y-DOTA(0),Tyr(3)]octreotide, [(177)Lu
      DOTA(0)Tyr(3)]octreotate, [(111)In-DOTA(0)]lanreotide and [(90)Y
      DOTA(0)]lanreotide can be used for this purpose.

PMID- 14713258
TI  - The importance of the measurement of circulating markers in patients with
      neuroendocrine tumours of the pancreas and gut.
AB  - The measurement of general and specific biochemical markers in patients with
      neuroendocrine tumours assists with diagnosis and gives an indication of the
      effectiveness of treatment and they may be used as prognostic indicators. There
      is much agreement that chromogranin A is the most universally helpful marker; it
      is found to be elevated in the circulation of about 90% of patients with
      metastatic neuroendocrine tumours and there are several excellent commercially
      available kits which give reliable estimations. Specific markers are useful for
      diagnosis also, and are helpful indicators of the effectiveness of treatment,
      particularly where tumour bulk may not change as much as tumour activity.
      Sporadic pancreatic neuroendocrine tumours may secrete more than one peptide and
      this indicates a worsening prognosis. Because of the wide variation in the
      progression of neuroendocrine tumours, a prognostic indicator gives a significant
      advantage to the clinician in order to facilitate optimum treatment at the
      optimum stage of disease. Both chromogranin A and neurokinin A have been used as
      powerful prognostic indicators for midgut carcinoid tumours.

PMID- 14713259
TI  - Ablative therapies for liver metastases of digestive endocrine tumours.
AB  - Hepatic metastases are frequently encountered in patients with digestive
      endocrine tumors and their presence plays an important role in quality of life
      and overall prognosis. Surgery is the treatment method of choice for hepatic
      metastases but this is frequently impossible due to the extent of disease.
      Systemic chemotherapy is offered to patients with diffuse and/or progressive
      liver metastases but results are disappointing especially in patients with
      metastases of midgut origin. In the latter patients with carcinoid syndrome,
      somatostatin analogs are frequently initially effective but their efficacy wanes
      due to disease progression and development of tachyphylaxis. Other therapeutic
      options in the treatment of hepatic metastases are locoregional strategies where
      vascular occlusion induces ischemia in these highly vascular tumors using either
      surgical or radiological techniques. Available methods include surgical ligation
      of the hepatic artery, transient hepatic ischemia or sequential hepatic
      arterialization. Trans-catheter arterial chemoembolization has proven effective
      in terms of long palliation and objective tumor responses. Other treatments aimed
      at regional destruction either alone or in combination with surgery include
      radiofrequency ablation and cryotherapy. The latter are usually important
      adjuncts to surgery and are usually reserved for limited disease.

PMID- 14713260
TI  - Surgery for midgut carcinoid.
AB  - Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia,
      because of its slow growth and relatively favourable prognosis. Nevertheless, the
      commonest cause of death in patients with carcinoid is advanced metastatic
      disease, and both clinical and epidemiological data indicate that the more
      effectively the disease is ablated, the more long-lasting the benefit.
      Multidisciplinary management of patients with carcinoid must consider inherited
      risk, possible multiple carcinoids and/or synchronous non-carcinoid cancer, and
      the use of a range of investigations that also evaluate the 10% of patients with
      carcinoid syndrome with or without valvular heart disease. Although primary size
      is correlated with the presence of nodal with or without liver metastases,
      carcinoid tumours <1 cm in diameter may be metastatic at presentation,
      particularly those arising within the small intestine. In the jejunum and ileum,
      resection of all sizes of carcinoid with local and regional nodes is preferred,
      to prevent nodal dissemination causing mesenteric ischaemia with or without
      infarction. Resection of nodal metastases should be undertaken in those with
      persistent or recurrent nodal disease if possible. Appendiceal and right colonic
      carcinoids are most effectively treated by right hemicolectomy with local and
      regional nodal clearance, as for adenocarcinoma. However, for most appendiceal
      carcinoids which are <1 cm in diameter and non-invasive, appendicectomy alone is
      sufficient. For appendiceal carcinoids 1-2 cm in diameter, histopathological
      assessment helps to determine the need for hemicolectomy. Liver resection has
      been followed by prolonged 5 year survival in several series and is recommended
      in appropriate patients to attempt cure or to debulk metastatic disease. Liver
      transplantation has had only qualified success in highly selected patients
      without extra-hepatic disease in whom other therapies have failed.

PMID- 14713261
TI  - Measurement of quality of life in carcinoid/neuroendocrine tumours.
AB  - Quality of life is multi-dimensional, including issues relating to symptoms from
      the disease but also social, emotional, functional and financial domains. Debate
      remains on the true definition of quality of life and its measurement. Quality of
      life measurements are best done by patients themselves, although, in some
      situations a proxy such as carer or relative can be substituted. Healthcare
      workers can over- or underestimate overall quality of life. Currently used
      devices for measuring quality of life in cancer include the European Organization
      for Research and Treatment of Cancer (EORTC) QLQ-C30, which is a generic tool for
      all cancers and which requires the use of add-on modules for specific cancers. We
      are developing a separate module for carcinoid/neuroendocrine tumours, in
      accordance with the EORTC guidelines on module development, which will be
      translated into five languages and will be available for use throughout Europe.

PMID- 14713262
TI  - Nurse developments in neuroendocrine tumour management.
AB  - Nurse developments in the management of neuroendocrine tumours have changed
      significantly over the past three years. At the Royal Free Hospital we set up the
      nurse specialist role due to the expansion of patients being referred to the
      specialist unit, and the obvious need for a nursing input into their care. The
      nurse specialist can make a significant contribution within the context of a
      multidisciplinary team especially in the production of guidelines and policies to
      ensure and maintain high standards of practice, education for the patient, and
      the provision of expertise and security that the patient requires when diagnosed
      with a rare disease.

PMID- 14713263
TI  - Carcinoid case presentation and discussion: the American perspective.
AB  - The rationale underlying an aggressive approach in the management of some
      carcinoid patients is explained and illustrated by the presented case of a middle
      aged man with advanced classic typical midgut carcinoid. The patient exhibited
      somatostatin receptor scintigraphy-positive massive liver metastases, carcinoid
      syndrome, severe tricuspid and pulmonic cardiac valve disease with congestive
      heart failure, ascites and malnutrition. He had been treated for several years
      with supportive medications and biotherapy including octreotide and alpha
      interferon but his tumor eventually progressed and his overall condition was
      markedly deteriorated when he first sought more aggressive treatment. This
      consisted of prompt replacement of both tricuspid and pulmonic valves, followed
      by hepatic artery chemoembolus (HACE) injection and then surgical tumor debulking
      including excision of the primary tumor in the small intestine. In addition,
      radiofrequency ablation was utilized to reduce the volume of metastases in the
      liver. Prophylactic cholecystectomy was also performed and a biopsy of tumor was
      submitted for cell culture drug resistance testing. This was followed by systemic
      chemotherapy utilizing the drug (docetaxel) which the in vitro studies suggested
      as most likely to be effective. His excellent response to this succession of
      treatments exemplifies the successful application of aggressive sequential multi
      modality therapy.

PMID- 14713264
TI  - Targeted radionuclide therapy for neuroendocrine tumours.
AB  - Evidence supporting the potential contribution of targeted radiotherapy to the
      management of neuroendocrine tumours is now strong. Acting systemically, this is
      an effective option for patients with inoperable or multi-site disease. Toxicity
      is generally low, being limited to reversible myelosuppression and theoretical
      nephrotoxicity. Prerequisites for treatment success include demonstration of high
      tumour uptake relative to non-target tissues on quantitative diagnostic
      radionuclide imaging and stable haematological and biochemical function. In
      addition to (131)I metaiodobenzylguanidine therapy, which is now well
      established, there is growing interest in radiolabelled peptide therapy using a
      range of somatostatin receptor analogues such as (90)Y DOTATOC and (90)Y
      lanreotide. The results of clinical experience are summarised and the direction
      for future research is discussed.

PMID- 14713265
TI  - Estrogen receptor corepressors -- a role in human breast cancer?
AB  - Estrogen receptor alpha (ERalpha) has an established role in promoting breast
      cancer. Transcriptional activation by ERalpha is a complex and multistep process,
      and it is influenced by coactivator and corepressor proteins that can either
      positively or negatively modulate ERalpha-mediated transcriptional activity.
      Corepressors are proposed to provide a counterbalance to the estrogen-induced
      transactivation, and represent a potential mechanism employed by the cell to
      regulate hormonal responses. In this review, we present evidence from tissue
      culture, animal and clinical studies, supporting the hypothesis that corepressors
      are crucial regulators of ERalpha-mediated action, and that their loss could
      promote breast cancer development and resistance to endocrine therapy. We propose
      that ERalpha corepressors play an important biological role by controlling the
      magnitude of the estrogen response, mediating antiestrogen inhibition of ERalpha,
      repressing DNA-bound ERalpha in the absence of the ligand, and conferring active
      repression of ERalpha-downregulated genes. Different ERalpha corepressors
      regulate steroid receptor activity through a variety of mechanisms, including
      formation of multiprotein complexes that are able to affect chromatin remodeling,
      histone deacetylation, or basal transcription. Other mechanisms include
      competition with coactivators, interference with DNA binding and ERalpha
      homodimerization, alteration of ERalpha stability, sequestration of ERalpha in
      the cytoplasm, and effects on RNA processing. Most ERalpha corepressors can
      control the receptor's activity through more than one mechanism, and it is
      possible that the synergy between different pathways cooperates to fully inhibit
      ERalpha transcriptional activity, and create an integrated response to a variety
      of different cellular signaling pathways. We will discuss the role of
      corepressors in tumor suppression and the link they might present between ERalpha
      regulation and DNA repair. Finally, we will discuss major challenges in the field
      and speculate on the exciting findings that await us in the next few years.

PMID- 14713266
TI  - Beta-catenin signaling in prostate cancer: an early perspective.
AB  - Further understanding of the molecular mechanisms responsible for prostate cancer
      (CaP) development and progression is paramount for overcoming the current
      diagnostic and therapeutic hurdles presented by this urologic disease. The beta
      catenin nuclear signaling molecule has been widely implicated as an oncogene in
      human cancer, including CaP. Pooling together knowledge gathered on the
      contributions of beta-catenin and other factors to human neoplasia may assist in
      the development of better strategies for management and treatment of prostate
      tumors of all stages (early, advanced/androgen-dependent, advanced/androgen
      independent). Although there is considerable lack of comprehension regarding the
      function of beta-catenin transcriptional activity in prostate tumors in vivo,
      recent evidence indicates the probability that beta-catenin contributes to
      multiple signaling pathways for which a causative role in CaP is already known.
      In this review, we will approach such pathway interactions, perhaps the most
      notable being androgen receptor (AR) signaling, in order to highlight those
      avenues through which beta-catenin may exert its cancer-related function. To the
      same end, we will draw attention to normal beta-catenin signaling in the
      prostate; however, as only very limited knowledge exists on this topic, much of
      the discussion will be correlative. Our final topic will concentrate on how,
      given realistic scenarios of androgen stimulation or absence in both normal and
      neoplastic prostate cells, nuclear beta-catenin may ultimately potentiate wnt
      cell-cell signaling and AR activities. Heightening our comprehension of beta
      catenin signaling mechanisms and its phenotypic consequences in CaP - and in
      normal prostate - may contribute to that body of knowledge which will eventually
      prove useful for devising more effective therapies.

PMID- 14713267
TI  - Deregulation of the IGF axis in cancer: epidemiological evidence and potential
      therapeutic interventions.
AB  - The IGF system performs a fundamental role in the regulation of cellular
      proliferation, differentiation and apoptosis. These diverse biological actions
      are mediated primarily by IGF association with the type I IGF receptor (IGF-IR),
      which is in turn regulated by a group of high-affinity IGF-binding proteins
      (IGFBP-1 to -6). All of the IGFBPs can have growth-inhibitory effects by
      competitively binding IGFs and preventing their association with the IGF-IR.
      IGFBP-3 is the most abundant binding protein in the circulation and controls the
      actions of the IGFs by regulating their distribution and bioavailability to
      target tissues. Disruptions in the balance of IGF system components leading to
      excessive proliferation and survival signals have been implicated in the
      development of different tumor types. Epidemiological evidence indicates that
      increased levels of IGF-I, reduced levels of IGFBP-3 or an increased ratio of IGF
      I to IGFBP-3 in the circulation are associated with an increased risk for the
      development of several common cancers, including those of the breast, prostate,
      lung and colon. The results of preclinical studies indicate that a diversity of
      interventions which antagonize IGF-IR signaling or augment IGFBP-3 function
      inhibit tumor cell growth in models of human cancers. A more comprehensive
      understanding of the interplay between cellular targets of the IGF system and
      antineoplastic agents will facilitate the development of novel strategies for the
      prevention and treatment of cancer.

PMID- 14713268
TI  - Resistance to different antiestrogens is caused by different multi-factorial
      changes and is associated with reduced expression of IGF receptor Ialpha.
AB  - Development of antiestrogen resistance is a major clinical problem, and therefore
      it is crucial to elucidate the mechanisms involved. To investigate whether gain
      of-function or loss-of-function mechanisms was most likely to be involved, cell
      fusion between the antiestrogen-sensitive MCF-7 and the ICI 164384- and ICI
      182780-resistant MCF-7/164(R)-5 cell lines was performed. Furthermore, a fusion
      cell line between the tamoxifen-resistant MCF-7/TAM(R)-1 and the MCF-7/164(R)-5
      cell line was established. A thorough investigation of growth parameters and
      expression of selected proteins (estrogen receptor-alpha (ERalpha), progesterone
      receptor (PR), Bcl-2, IGF-binding protein-2 (IGFBP2) and IGF receptor Ialpha (IGF
      IRalpha)) in the fusion partners and fusion cells revealed that both gain- and
      loss-of-function changes occurred, and that the mechanisms resulting in
      resistance to the two antiestrogens were different. This multi-factoriality of
      antiestrogen resistance is promising in relation to sequential treatment of
      breast cancer patients with different types of endocrine therapy. Furthermore, we
      found an association between antiestrogen resistance and reduced IGF-IRalpha
      expression. Overall, the data presented in this report support the usefulness of
      cell fusion to clarify the mechanisms involved in development of resistance to
      the pure antiestrogens ICI 182780 and ICI 164384 and the selective ER modulator
      tamoxifen and suggest IGF-IRalpha as a new sensitive marker for response to
      antiestrogen treatment.

PMID- 14713269
TI  - Two somatic TSH receptor mutations in a patient with toxic metastasising
      follicular thyroid carcinoma and non-functional lung metastases.
AB  - In a 59-year-old patient, thyroid follicular cancer was diagnosed in two right
      sided toxic thyroid nodules, which had presented clinically as unilateral thyroid
      autonomy. In addition, the patient had histologically proven lung metastases of
      thyroid cancer; however, these failed to exhibit iodine uptake and were resistant
      to radioiodine treatment. The functional activity of the thyroid nodules prompted
      us to screen for TSH receptor (TSHR) mutations, and the histological diagnosis of
      follicular carcinoma led us to search for the PAX8-PPARgamma1 rearrangement and
      mutations in the ras genes. Each thyroid nodule harboured a different TSHR
      mutation (large nodule, Asp633Tyr; small nodule, Phe631Ile). Presence of both
      mutations in one sample suggestive of local invasion of a thyroid carcinoma could
      not be demonstrated, although several specimens from different nodule locations
      were screened. Only the wild-type TSHR sequence was identified in the
      histologically normal left thyroid lobe, and no genetic alterations were found in
      the other investigated genes. No TSHR mutations were detected in the pulmonary
      metastases. This is the first case report of a patient with toxic follicular
      thyroid carcinoma harbouring two different TSHR mutations and presenting with non
      functional lung metastases.

PMID- 14713270
TI  - Quality of life and psychometric functionality in patients with differentiated
      thyroid carcinoma.
AB  - We studied the psychological performance and the quality of life in patients with
      differentiated thyroid carcinoma, either during treatment with chronic
      suppressive doses of levothyroxine, or during the withdrawal of levothyroxine
      needed to perform whole-body scanning with radioactive iodine, with those of
      appropriate healthy controls. Eighteen women with differentiated thyroid
      carcinoma and 18 euthyroid age-matched healthy women were recruited. Patients
      were studied the day before levothyroxine withdrawal (when in chronic mild or
      subclinical hyperthyroidism), 4-7 days later (when most patients had normal serum
      free thyroxine and free triiodothyronine levels), and the day before scanning
      (when in profound hypothyroidism). Controls were studied at one time point. When
      compared with controls, patients presented with impairment of several indexes
      during chronic suppressive levothyroxine therapy (total score, emotional, sleep,
      energy and social of the Nottingham Health Profile; mental health, general health
      and social function of the SF-36, and total score on Wais Digit Span; P<0.05 for
      all comparisons). Also, quality of life indexes (19 of 21 scores), cognitive
      tests (6 of 12 scores), and affective and physical symptoms visual mental scales
      (18 of 19) worsened during profound hypothyroidism (P<0.05 for all comparisons).
      Quality of life and cognitive performance were almost comparable with those of
      euthyroid controls when most patients had normal free thyroxine and
      triiodothyronine levels. In conclusion, quality of life and psychometric
      functionality in patients with differentiated thyroid carcinoma is not only
      affected by withdrawal of levothyroxine but also by long-term treatment with
      supraphysiological doses of levothyroxine.

PMID- 14713271
TI  - Evolving criteria for post-operative biochemical remission of acromegaly: can we
      achieve a definitive cure? An audit of surgical results on a large series and a
      review of the literature.
AB  - Criteria to define the biochemical remission of acromegaly following surgery have
      changed over the years, and the current use of stringent criteria needs a
      critical re-evaluation of the surgical results. On the other hand, few data are
      currently available concerning the possible impact of pituitary surgery on the
      quality of life of operated acromegalic patients. In this prospective study, we
      wished to evaluate the initial outcome and long-term recurrence rate in a large
      series of acromegalic patients operated on by transsphenoidal surgery (TSS), to
      carefully analyse predictive factors for surgical outcome and to point out
      possible additional effects of surgery in these patients. Ninety-two out of 98
      operated patients could be considered for follow-up. Biochemical remission was
      strictly defined as plasma GH levels <1 ng/ml during an oral glucose tolerance
      test (OGTT) and normalisation of age-related IGF-I levels. Hormonal assessment,
      including an OGTT, was performed 6 months following surgery and then annually to
      evaluate pituitary function. Fifty-five per cent of patients achieved a
      biochemical remission of acromegaly. The remission rate at 6 months was 80% for
      patients with microadenoma and 50% for macroadenoma. Univariate analysis showed
      that a large extrasellar extension, preoperative high GH levels and dural
      invasion were correlated with a poor outcome of surgery while, according to
      multivariate analysis, only invasion of cavernous sinus and preoperative GH
      levels > 10 ng/ml were independent negative predictors. Mortality was 0% and the
      overall complication rate was about 10%. Pituitary function worsened in five
      patients but improved in 16 out of 30 patients with preoperative pituitary
      defects. No recurrence was observed during a median follow-up of about 8 years.
      We conclude that TSS is able to achieve a biochemical remission in more than half
      of acromegalic patients, and that the current criteria for remission seem to
      indicate a cure in most cases.

PMID- 14713272
TI  - The gene expression profiling of sporadic pheochromocytoma and novel full-length
      cDNAs cloning.
AB  - Pheochromocytoma is a chromaffin cell neoplasm that typically causes symptoms and
      signs of episodic catecholamine release. Pheochromocytoma can be divided into two
      types: familial and sporadic. The molecular mechanisms involved in familial
      pheochromocytoma have been unraveled, but the detailed molecular mechanism of
      sporadic pheochromocytoma remains unknown. The present study thus aimed at
      characterization of gene expression profiling of sporadic pheochromocytoma using
      expressed sequence tags (ESTs), and established a preliminary catalog of genes
      expressed in the tumor. In total, 4115 ESTs were generated from the tumor
      library. The gene expression profilings of the pheochromocytoma and the normal
      adrenal gland were compared, and 341 genes were identified to be significantly
      expressed differently between the two libraries. Interestingly, 16 known genes
      participating in cell division or apoptosis were notably differently expressed
      between the tumor and the normal adrenal gland. Twenty-four novel full-length
      cDNAs were cloned from the tumor library and five of them were significantly up
      regulated in the tumor. Some of them may be involved in the tumorigenesis of
      pheochromocytoma. The sequence data of ESTs and novel full-length cDNAs described
      in this paper have been submitted to the GeneBank library.

PMID- 14713273
TI  - Clinical and hormonal characteristics of central hypothyroidism at diagnosis and
      during follow-up in adult patients.
AB  - OBJECTIVE: We studied the clinical and hormonal profiles of patients with central
      hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the
      influence of other pituitary hormone replacement therapies. METHODS: We reviewed
      medical records of 108 adult patients with child-onset (CO; n=26) or adult-onset
      (AO; n=82) CH. RESULTS: At diagnosis, the most frequently reported symptoms were
      fatigue and headaches in AO patients, and growth retardation in CO patients.
      Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%.
      Serum free thyroxine (fT(4)) was usually reduced, but remained within the low
      normal range in 28% of the study population (mostly CO patients). Similarly,
      serum total T(4) (tT(4)), total triiodothyronine (tT(3)) and free T(3) (fT(3))
      were found to be within the normal range in significant subsets of patients.
      Interestingly, the clinical and biochemical characteristics of CH patients with
      normal f/t T(4) levels were not different from those of the patients with low
      fT(4) values. The thyroid hormonal profile was not influenced by gender, etiology
      or by the number of hormone deficiencies. At last evaluation, the mean dose of L
      T(4) was 1.6+/-0.5 microg/kg/day and was negatively correlated to current age
      (P<0.001) but positively correlated to the number of hormone deficiencies
      (P<0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT(4)
      in 94%, but normal fT(3) in only 49% of them. Male GH-treated patients and
      estrogen-treated females needed a higher L-T(4) dose compared with non-treated
      patients. CONCLUSIONS: fT(4) is clearly the best indicator of CH, but remains in
      the low normal range in a significant subset of patients, especially in those
      with CO disease. Adequacy of therapy is mostly reflected by the combination of
      upper normal fT(4) and low normal fT(3) levels. Pituitary hormone replacement
      therapy may require an adjustment of T(4) treatment, as female patients under
      estrogen treatment and male patients under GH treatment will need a higher T(4)
      dose in order to remain in the euthyroid range.

PMID- 14713274
TI  - Prevalence of calcium sensing receptor autoantibodies in patients with sporadic
      idiopathic hypoparathyroidism.
AB  - OBJECTIVE: The pathogenesis of sporadic idiopathic hypoparathyroidism is unclear.
      The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium
      homeostasis and is the candidate autoantigen in hypoparathyroidism associated
      with autoimmune polyglandular endocrinopathy syndrome. We therefore looked for
      antibodies (Ab) against the CaSR in patients with sporadic idiopathic
      hypoparathyroidism and their association, if any, with the major
      histocompatibility complex (MHC) class II human leukocyte antigen (HLA)-DR
      haplotypes. METHODS: The subjects included 51 patients with sporadic idiopathic
      hypoparathyroidism and 45 healthy controls. Investigations included computerised
      tomography, serum calcium, phosphorus, thyroxine, TSH, cortisol, intact
      parathyroid hormone (iPTH), ACTH and thyroid peroxidase (TPO) and adrenal
      antibodies. The CaSRAb were assayed in patients' sera by Western blot. Genotyping
      of the HLA-DR locus was performed using PCR and sequence-specific oligonucleotide
      probes. RESULTS: Intracranial calcification and cataract were present in 76.5%
      and 41.1% of the patients respectively and 62.7% had convulsions. Autoantibodies
      against the 168 kDa CaSR protein were demonstrated in the serum of 49.0% of the
      patients and in 13.3% of the controls (P<0.001). Pre-incubating serum samples
      from the CaSRAb-positive patients with parathyroid membrane produced a 90%
      decrease in the band intensity. HLA-DRB1*01 and DRB1*09 alleles were
      significantly associated with idiopathic hypoparathyroidism (relative risk of
      7.8, P=0.001). The frequency of HLA-DRB1*09 and DRB1*10 alleles tended to be
      higher in patients positive for the CaSRAb. There was no significant difference
      in the frequency of occurrence of convulsions, cataract, intracranial
      calcification, calcium:phosphorus ratio, and iPTH levels between patients with
      and without CaSRAb. CONCLUSION: 49.0% of the patients studied had serological
      evidence of organ-specific autoimmunity against the CaSR protein. The occurrence
      of CaSRAb and the HLA-DR associations imply an autoimmune component to the
      disease, but the primary role of the CaSRAb in the pathogenesis of the disease
      needs to be assessed further.

PMID- 14713275
TI  - Persistent disease after surgery for primary hyperparathyroidism: the long-term
      outcome.
AB  - OBJECTIVE: Nineteen patients with persistent primary hyperparathyroidism were
      investigated to evaluate their clinical and laboratory status a long time after
      treatment was ended. The risk of persistent disease and need for extensive
      surgery for cure, i.e. more than two neck operations, or mediastinal exploration,
      was also evaluated. DESIGN: The medical records of 896 consecutive patients
      operated on for primary hyperparathyroidism were scrutinised at follow-up, a mean
      of 10.3 Years after surgery. Data on state of health, medication, bone fractures
      and other diagnoses were collected by use of a questionnaire. There were 600
      patients still alive, among whom 13 had persistent disease and they were compared
      with 509 patients who were cured and without any suspicion of recurrent disease,
      according to laboratory examination. RESULTS: Serum calcium and creatinine values
      had with few exceptions remained stable over the Years. In five patients, serum
      calcium levels were within the normal range at follow-up. Still, all 19 patients
      were considered hyperparathyroid. They had substantial cardiovascular morbidity,
      and their state of health was not as good as that of the patients who were
      surgically cured. After one operation, 5.5% (95% confidence interval (CI) 4.0
      7.2%) had persistent disease, and 2.1% after reoperation. Extensive surgery for
      cure was performed in 2% of the patients (95% CI 1.1-3.2%). CONCLUSIONS: We found
      that the state of health was significantly better for patients with cured primary
      hyperparathyroidism than for patients with persistent disease, but serious
      deterioration of laboratory values was uncommon. The result of the present study
      supports surgical treatment.

PMID- 14713276
TI  - Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic
      hormones in acromegaly.
AB  - OBJECTIVE: Ghrelin, a gut-brain peptide involved in the control of energy
      homeostasis, affects antero-pituitary and gastro-entero-pancreatic (GEP) hormone
      secretion in healthy subjects. We aimed to verify whether such hormonal responses
      are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin
      and abnormal GEP hormone levels. DESIGN AND METHODS: The effect of ghrelin (3.3
      microg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL),
      adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS)
      and pancreatic polypeptide (PP) circulating levels were evaluated in seven non
      diabetic patients with newly diagnosed acromegaly and in nine healthy controls.
      RESULTS: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in
      all normal (from 1.6+/-0.6 to 52.9+/-7.8 and from 9.7+/-0.8 to 24.2+/-4.8
      microg/l (means+/-S.E.M.), respectively) and acromegalic subjects (from 11.2+/
      4.9 to 91.6+/-21.0 and from 42.9+/-26.1 to 113.8+/-79.0 microg/l, respectively).
      Both plasma ACTH and serum cortisol levels rose significantly in the controls,
      whereas the cortisol response was blunted in the acromegalic patients. Glucose
      levels rose earlier and insulin levels fell later in all subjects, with a
      significantly greater net insulin decrease in acromegalic than in healthy
      subjects (-80+/-21 vs -17+/-4 pmol/l, P<0.01). A prompt PP rise and a biphasic SS
      response occurred in all controls, whereas in the acromegalic group the PP
      response (from 26.1+/-5.0 to 92.2+/-39.0 pmol/l) and the SS response (from 11.9+/
      3.0 to 19.7+/-4.0 ng/l) were quite variable. CONCLUSIONS: Ghrelin affects both
      pituitary and GEP hormones in acromegalic patients as in normal subjects. These
      findings suggest that ghrelin actions on the energy balance are mediated by
      complex interactive endocrine loops that involve also the gut and pancreas.

PMID- 14713277
TI  - Oleic acid from cooking oils is associated with lower insulin resistance in the
      general population (Pizarra study).
AB  - AIM: To evaluate the relation between type of dietary fatty acid and degree of
      insulin resistance. DESIGN: A cross-sectional study. METHODS: Anthropometrical
      data were measured in 538 subjects, aged 18-65 Years, selected randomly from the
      municipal census of Pizarra (Spain). An oral glucose tolerance test (OGTT) was
      given to all subjects and measurements were made of glycemia, insulinemia and the
      proportion of fatty acids in plasma phospholipids. Insulin resistance (IR) was
      estimated by homeostasis model assessment. Samples of cooking oil being used were
      obtained from the kitchens. The strength of association between variables was
      measured by calculating the odds ratio (OR) from logistic models, and the
      relationships were measured by linear correlation coefficients. RESULTS: Insulin
      resistance was significantly less in people who used olive oil compared with
      those who used sunflower oil or a mixture. Statistical significance remained in
      the group of people with normal OGTT after adjusting for obesity. In the whole
      sample, IR correlated negatively with the concentration of oleic acid (r=-0.11;
      P=0.02) and positively with that of linoleic acid (r=0.10; P=0.02) from the
      cooking oil. In subjects with normal OGTT, IR correlated negatively with oleic
      acid from cooking oil (r=-0.17; P=0.004) and from plasma phospholipids (r=-0.11;
      P=0.01) and positively with the concentration of linoleic acid in cooking oil
      (r=0.18; P=0.004) and plasma phospholipids (r=0.12; P=0.005). The risk (OR) of
      having raised IR was significantly lower in people who consumed olive oil, either
      alone (OR=0.50) or mixed (OR=0.52) compared with those who consumed only
      sunflower oil. CONCLUSION: There is an association between the intake of oleic
      acid, the composition of oleic acid in plasma phospholipids and peripheral
      insulin action.

PMID- 14713278
TI  - A comparison of in vitro bioassays to determine cellular glucocorticoid
      sensitivity.
AB  - An altered cellular glucocorticoid (GC) sensitivity is associated with several
      pathophysiological conditions such as asthma, diabetes, or rheumatoid arthritis.
      Several bioassays have been developed and employed to assess cellular GC
      sensitivity of peripheral blood mononuclear cells (PBMC), but correlations
      between these have rarely been investigated. We have compared four mitogen-based
      assays and an FK506 binding protein 51 (FKBP51) mRNA induction assay, using ten
      controls and a GC-resistant patient. The mitogen-based assays were performed
      using either diluted whole blood or isolated PBMC, and showed relatively large
      assay variations for the parameters maximal effect and half-maximal effect
      concentration. The FKBP51 assay showed smaller intra-assay and within-individual
      variation compared with the mitogen-based assays. The whole blood-based mitogen
      assays and the FKBP51 assay clearly discriminated the GC-resistant patient from
      the controls but, in contrast to expectations, both PBMC-based mitogen assays did
      not. The GC-induced FKBP51 mRNA increase in PBMC may be an alternative to
      determine an altered individual GC sensitivity with several advantages as
      compared with mitogen-based assays, such as the use of unstimulated PBMC, and a
      better intra- and inter-individual reproducibility.

PMID- 14713279
TI  - Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in
      autoimmune Addison's disease are mainly immunoglobulin G1.
AB  - OBJECTIVE: Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21
      hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic
      markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes
      (APS) types I and II. The characterization of autoantibody (IgG) subclasses may
      reveal information on how tIssue destruction takes place; therefore, IgG subtypes
      of anti-21OH and anti-SCC antibodies from sera of patients with Addison's
      disease, APS I and APS II were determined using recombinant 21OH and SCC.
      METHODS: SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the
      Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full
      length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed
      in insect cells by using the baculovirus expression system bac-to-bac. Western
      blots were used to investigate the IgG subtype(s) of the autoantibodies against
      21OH and SCC in patients and healthy blood donors. RESULTS: All anti-SCC positive
      sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten
      also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies
      exclusively against IgG1. Sera from 20 healthy subjects did not show any
      reactivity against 21OH or SCC. CONCLUSIONS: The finding of a predominating IgG1
      response against 21OH and SCC may suggest that T helper (Th) cells of the Th1
      subclass are involved in destruction of the adrenal cortex in patients with
      autoimmune Addison's disease.

PMID- 14713280
TI  - Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in
      hypogonadal men.
AB  - OBJECTIVE: A phase I single centre, open label study of the pharmacokinetics and
      tolerability of a buccal testosterone tablet (COL 1621) was carried out. DESIGN:
      Twelve testosterone-deficient males were treated with the buccal tablet twice
      daily for 7 consecutive days. Multiple blood samples were drawn for testosterone,
      dihydrotestosterone (DHT), bioavailable testosterone and sex hormone-binding
      globulin (SHBG). RESULTS: After COL 1621, means+/-S.D. serum testosterone level
      increased to a peak concentration of 26.6+/-5.8 nmol/l (7.7+/-1.7 ng/ml) at 4.8+/
      5.8 h and stayed in the eugonadal range. Steady state was achieved within the
      first 24 h and was maintained in the normal range. The bioavailable testosterone,
      DHT and free testosterone index followed a pattern very similar to that of
      testosterone. The mean serum testosterone to DHT ratio was within the normal male
      range throughout treatment. There was only one treatment-related adverse event
      (headache). Two-thirds of patients indicated that treatment with COL 1621 was
      acceptable and that the tablet was convenient to use. Six patients (50.0%)
      preferred COL 1621 to their previous testosterone replacement therapy, two
      patients gave preference to their previous treatment and three patients found
      both treatments to be equally acceptable. Data for one patient was not available.
      CONCLUSION: We conclude that COL 1621 can efficiently elevate serum testosterone
      and DHT levels in hypogonadal men within the first day of application, achieve a
      steady state within 24 h and maintain serum testosterone in the normal range with
      a twice-daily treatment regimen. COL 1621 provides an effective alternative oral
      testosterone replacement therapy that gives physiological levels of testosterone
      and is well tolerated by the patients.

PMID- 14713281
TI  - Association of endogenous testosterone with blood pressure and left ventricular
      mass in men. The Tromso Study.
AB  - OBJECTIVE: To test the hypothesis that lower endogenous testosterone levels are
      associated with higher blood pressure, left ventricular mass, and left
      ventricular hypertrophy. DESIGN: Population-based cross-sectional study. METHODS:
      Sex hormone levels, measured by immunoassay, anthropometric measurements and
      resting blood pressure were studied in 1548 men aged 25-84 Years;
      echocardiography was completed in 1264 of these men. Partial correlations and
      multiple regressions were used to estimate the associations between sex hormones,
      blood pressure and left ventricular mass by height. Analyses of variance and
      covariance were used to compare men with categorical hypertension and left
      ventricular hypertrophy. RESULTS: In age-adjusted partial correlations, total
      testosterone and sex hormone-binding globulin (SHBG) were each inversely
      associated with systolic blood pressure (SBP) (P<0.001). Men with categorical
      hypertension (SBP> or =140 or diastolic blood pressure (DBP)> or =90 mmHg) had
      lower levels of total and free testosterone and SHBG before (P<0.001, P=0.011 and
      P<0.001, respectively) and after (P<0.001, P=0.035 and P=0.002, respectively)
      adjusting for body mass index (BMI). Total testosterone and SHBG were each
      inversely associated with left ventricular mass (P<0.001), and men with left
      ventricular hypertrophy had significantly lower levels of total testosterone
      (P=0.042) and SHBG (P=0.006); these associations were no longer significant after
      adjusting for BMI. CONCLUSION: The results of the present study are consistent
      with the hypothesis that lower levels of testosterone in men are associated with
      higher blood pressure, left ventricular mass, and left ventricular hypertrophy.
      The reduced associations after adjusting for BMI suggest that the association of
      low testosterone levels with blood pressure and left ventricular mass is mediated
      by obesity.

PMID- 14713282
TI  - Evidence for processing of compact insoluble thyroglobulin globules in relation
      with follicular cell functional activity in the human and the mouse thyroid.
AB  - OBJECTIVE: Thyroglobulin (Tg) is stored within the follicular lumen mainly in a
      soluble form, but globules made of insoluble multimers are also present and
      considered to be a mechanism to store prohormone at high concentration. We
      investigated the immunohistochemical properties of these intrafollicular globules
      and their possible processing by thyroid cells upon stimulation in the human and
      in the mouse. DESIGN: Human thyroids (normal, Graves' disease and hot adenomas)
      and thyroids from old ICR mice without or with goitrogenic treatment were
      processed for light microscopy. METHODS: Immunohistochemistry for Tg with a
      polyclonal antibody and two monoclonal antibodies, one specific for thyroxine
      rich-iodinated Tg and the other recognizing Tg independently of its iodine level,
      staining with periodic-acid-schiff, and binding of lectins specific for mannose
      and sialic acid were performed on all tIssue sections. Intrafollicular globules
      were quantified, with distinction between 'active' or 'hot' and 'hypofunctioning'
      or 'cold' follicles. RESULTS: In normal human and old mouse thyroids, the
      intrafollicular globules were strongly stained with PAS, but negative for the
      three anti-Tg antibodies and the two lectin-binding assays, while the surrounding
      soluble Tg was positive. In normal human tIssue, globules were more frequent in
      'hypofunctioning' than in 'active' follicles. They were exceptional in Graves'
      disease and hot adenomas. In old mice, Tg globules were more frequent in 'cold'
      than in 'hot' follicles. Along with the goitrogen treatment, they became fewer,
      fragmented and more often present in follicles with a 'hot' aspect. CONCLUSIONS:
      Upon TSH stimulation, thyrocytes become able to process colloid globules
      suggesting that this stock of Tg can be used in vivo for thyroid hormone
      synthesis.

PMID- 14713283
TI  - Influence of fluor salts, hormone replacement therapy and calcitonin on the
      concentration of insulin-like growth factor (IGF)-I, IGF-II and transforming
      growth factor-beta 1 in human iliac crest bone matrix from patients with primary
      osteoporosis.
AB  - OBJECTIVE: Data from cell culture experiments suggest that local growth factors
      (GFs) may mediate the effects of estrogens, calcitonin or fluor ions on the
      skeleton. To assess the in vivo relevance of the in vitro reports, the effect of
      fluor salts, hormone replacement therapy (HRT) and calcitonin on the
      concentrations of IGF-I, IGF-II and transforming growth factor (TGF)-beta 1 in
      bone matrix extracts from osteoporotic patients was evaluated. DESIGN: Iliac
      crest bone biopsies were obtained from 170 patients (76 men and 94 women) with
      primary osteoporosis aged 55.5+/-0.8 Years. METHODS: Bone matrix extraction was
      performed based on a guanidine-HCl/ethylendiamine-tetra-acetic acid method.
      RESULTS: In comparison with age- and body mass index (BMI)-matched controls, no
      influence of long-term therapy with fluor ions (n=41) or calcitonin (n=16) on the
      bone matrix concentration of GFs was noticed. Postmenopausal women with
      osteoporosis on HRT (n=39) had lower skeletal IGF-I but not IGF-II levels as
      compared with age- and BMI-matched non-users. However, the lower rate of bone
      turnover in women with HRT may account for this difference, since the
      significance was lost after adjustment for alkaline phosphatase. Likewise, a
      tendency for lower TGF-beta 1 levels was observed in HRT users as compared with
      non-users but was lost after adjustment for bone turnover. None of the therapies
      influenced the serum levels of GFs when patients receiving continuous therapy for
      at least 1 Year before bone biopsy were considered. CONCLUSIONS: Our data suggest
      no direct effect of fluor therapy on skeletal GFs levels. At the concentrations
      used, neither HRT nor calcitonin appeared to exert any significant influence on
      serum or bone matrix GF levels.

PMID- 14713284
TI  - All the studies on hyperprolactinemia should not forget to consider the possible
      presence of macroprolactinemia.

PMID- 14713285
TI  - Insulin, food restriction and the extension of lifespan: the mechanism of
      longevity.

PMID- 14713286
TI  - Identification of an orphan guanylate cyclase receptor selectively expressed in
      mouse testis.
AB  - We have identified a novel membrane form of guanylate cyclase (GC) from a mouse
      testis cDNA library and termed it mGC-G (mouse GC-G) based on its high sequence
      homology to rat GC-G. It encodes a potential type I transmembrane receptor, with
      the characteristic domain structure common to all members of the family of
      membrane GCs, including an extracellular, putative ligand-binding domain, a
      single membrane-spanning segment and cytoplasmic protein kinase-like and cyclase
      catalytic domains. Real-time quantitative reverse transcriptase--PCR and Northern
      blot analyses showed that mGC-G is highly and selectively expressed in mouse
      testis. Phylogenetic analysis based on the extracellular protein sequence
      revealed that mGC-G is closely related to members of the subfamily of natriuretic
      peptide receptor GCs. When overexpressed in HEK-293T cells (human embryonic
      kidney 293T cells) or COS-7 cells, mGC-G manifests as a membrane-bound
      glycoprotein, which can form either homomeric or heteromeric complexes with the
      natriuretic peptide receptor GC-A. It exhibits marked cGMP-generating GC
      activity; however, notably, all ligands known to activate other receptor GCs
      failed to stimulate enzymic activity. The unique testis-enriched expression of
      mGC-G, which is completely different from the broader tissue distribution of rat
      GC-G, suggests the existence of as-yet-unidentified ligands and unappreciated
      species-specific physiological functions mediated through mGC-G/cGMP signalling
      in the testis.

PMID- 14713287
TI  - Comparative analysis of tandem C2 domains from the mammalian synaptotagmin
      family.
AB  - Intracellular membrane traffic is governed by a conserved set of proteins,
      including Syts (synaptotagmins). The mammalian Syt family includes 15 isoforms.
      Syts are membrane proteins that possess tandem C2 domains (C2AB) implicated in
      calcium-dependent phospholipid binding. We performed a pair-wise amino acid
      sequence comparison, together with functional studies of rat Syt C2ABs, to
      examine common and divergent properties within the mammalian family. Sequence
      analysis indicates three different C2AB classes, the members of which share a
      high degree of sequence similarity. All the other C2ABs are highly divergent in
      sequence. Nearly half of the Syt family does not exhibit calcium/phospholipid
      binding in comparison to Syt I, the major brain isoform. Syts do, however,
      possess a more conserved function, namely calcium-independent binding to target
      SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein
      receptor) heterodimers. All tested isoforms, except Syt XII and Syt XIII, bound
      the target SNARE heterodimer comprising syntaxin 1 and SNAP-25 (25 kDa
      synaptosome-associated protein). Our present study suggests that many Syt
      isoforms can function in membrane trafficking to interact with the target SNARE
      heterodimer on the pathway to calcium-triggered membrane fusion.

PMID- 14713288
TI  - Inducible cAMP early repressor (ICER) in the nervous system--a transcriptional
      regulator of neuronal plasticity and programmed cell death.
AB  - The acronym ICER (inducible cAMP early repressor) refers to a group of four
      proteins produced from the CREM/ICER gene due to use of an internal promoter (P2)
      placed in an intron of the CREM (cAMP responsive element modulator) gene. The
      ICER proteins contain DNA binding/leucine zipper domains that make them
      endogenous inhibitors of transcription driven by CREB (cAMP responsive element
      binding protein) and its cognates, CREM and ATF-1 (activating transcription
      factor-1). ICER expression is inducible in the brain and in neuronal culture by a
      variety of stimuli. As a CREB antagonist, ICER appears to be of pivotal
      importance in neuronal plasticity and programmed cell death.

PMID- 14713289
TI  - Modulation of nerve growth factor-induced activation of MAP kinase in PC12 cells
      by inhibitors of nitric oxide synthase.
AB  - Nerve growth factor (NGF) increases expression of nitric oxide synthase (NOS)
      isozymes leading to enhanced production of nitric oxide (NO). NOS inhibitors
      attenuate NGF-mediated increases in cholinergic gene expression and neurite
      outgrowth. Mechanisms underlying this are unknown, but the mitogen-activated
      protein (MAP) kinase pathway plays an important role in NGF signaling. Like NGF,
      NO donors activate Ras leading to phosphorylation of MAP kinase. The present
      study investigated the role of NO in NGF-mediated activation of MAP kinase in
      PC12 cells. Cells were treated with 50 ng/mL NGF to establish the temporal
      pattern for rapid and sustained activation phases of MAP kinase kinase (MEK)-1/2
      and p42/p44-MAP kinase. Subsequently, cells were pretreated with NOS inhibitors
      Nomega-nitro-L-arginine methylester and s-methylisothiourea and exposed to NGF
      for up to 24 h. NGF-induced activation of MEK-1/2 and p42/p44-MAP kinase was not
      dependent on NO, but sustained phosphorylation of MAP kinase was modulated by NO.
      This modulation did not occur at the level of Ras-Raf-MEK signaling or require
      activation of cGMP/PKG pathway. NOS inhibitors did not affect NGF-mediated
      phosphorylation of MEK. Expression of constitutively active-MEKK1 in cells led to
      phosphorylation of p42/p44-MAP kinase and robust neurite outgrowth;
      constitutively active-MKK1 also caused differentiation with neurite extension.
      NOS inhibitor treatment of cells expressing constitutively active kinases did not
      affect MAP kinase activation, but neurite outgrowth was attenuated. NOS
      inhibitors did not alter NGF-mediated nuclear translocation of phospho-MAP
      kinase, but phosphorylated kinases disappeared more rapidly from NOS inhibitor
      treated cells suggesting greater phosphatase activity and termination of
      sustained activation of MAP kinase.

PMID- 14713290
TI  - Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3
      kinase and protein kinase C leads to hyperphosphorylation of tau and impairment
      of spatial memory.
AB  - Neurofibrillary tangles (NFTs) consisting of the hyperphosphorylated microtubule
      associated protein tau are a defining pathological characteristic of Alzheimer's
      disease (AD). Hyperphosphorylation of tau is hypothesized to impair the
      microtubule stabilizing function of tau, leading to the formation of paired
      helical filaments and neuronal death. Glycogen synthase kinase-3 (GSK-3) has been
      shown to be one of several kinases that mediate tau hyperphosphorylation in
      vitro. However, molecular mechanisms underlying overactivation of GSK-3 and its
      potential linkage to AD-like pathologies in vivo remain unclear. Here, we
      demonstrate that injection of wortmannin (a specific inhibitor of phosphoinositol
      3 kinase) or GF-109203X (a specific inhibitor of protein kinase C) into the left
      ventricle of rat brains leads to overactivation of GSK-3, hyperphosphorylation of
      tau at Ser 396/404/199/202 and, most significantly, impaired spatial memory. The
      effects of wortmannin and GF-109203X are additive. Significantly, specific
      inhibition of GSK-3 activity by LiCl prevents hyperphosphorylation of tau, and
      spatial memory impairment resulting from PI3K and PKC inhibition. These results
      indicate that in vivo inhibition of phosphoinositol-3 kinase and protein kinase C
      results in overactivation of GSK-3 and tau hyperphosphorylation and support a
      direct role of GSK-3 in the formation of AD-like cognitive deficits.

PMID- 14713291
TI  - Ebselen inhibits NO-induced apoptosis of differentiated PC12 cells via inhibition
      of ASK1-p38 MAPK-p53 and JNK signaling and activation of p44/42 MAPK and Bcl-2.
AB  - Ebselen, a selenium-containing heterocyclic compound, prevents ischemia-induced
      cell death. However, the molecular mechanism through which ebselen exerts its
      cytoprotective effect remains to be elucidated. Using sodium nitroprusside (SNP)
      as a nitric oxide (NO) donor, we show here that ebselen potently inhibits NO
      induced apoptosis of differentiated PC12 cells. This was associated with
      inhibition of NO-induced phosphatidyl Serine exposure, cytochrome c release, and
      caspase-3 activation by ebselen. Analysis of key apoptotic regulators during NO
      induced apoptosis of differentiated PC12 cells showed that ebselen blocks the
      activation of the apoptosis signaling-regulating kinase 1 (ASK1), and inhibits
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun N
      terminal protein kinase (JNK). Moreover, ebselen inhibits NO-induced p53
      phosphorylation at Ser15 and c-Jun phosphorylation at Ser63 and Ser73. It appears
      that inhibition of p38 MAPK and p53 phosphorylation by ebselen occurs via a thiol
      redox-dependent mechanism. Interestingly, ebselen also activates p44/42 MAPK, and
      inhibits the downregulation of the antiapoptotic protein Bcl-2 in SNP-treated
      PC12 cells. Together, these findings suggest that ebselen protects neuronal cells
      from NO cytotoxicity by reciprocally regulating the apoptotic and antiapoptotic
      signaling cascades.

PMID- 14713292
TI  - Molecular cloning, characterization and brain mapping of the melanocortin 5
      receptor in the goldfish.
AB  - The melanocortin 5 receptor (MC5R) is activated by melanocyte-stimulating
      hormones (MSHs) and has a widespread tissue distribution, while its detailed
      central expression pattern and brain functions are fairly unknown. We report
      cloning, pharmacological characterization, tissue distribution and detailed brain
      mapping of melanocortin 5 receptor in goldfish (gMC5R). The goldfish orthologue
      protein is 69% identical to human MC5R and is conserved in important functional
      domains. The gMC5R showed similar potency to alpha-, beta- and gamma-MSH peptides
      in radioligand binding as the mammalian orthologues, while MTII and HS024 were
      both agonists at this receptor. The gMC5R-mRNA was found in the peripheral
      tissues including kidney, spleen, skin and retina, with low expression levels in
      the intestine, fat, muscle, gill, pituitary and ovary. In situ hybridization
      studies demonstrated that gMC5R transcripts are widely distributed in the
      goldfish brain. The gMC5R expression was found in ventral telencephalon, pre
      optic area, dorsal and ventral thalamus, infundibular hypothalamus, posterior
      tuberculum, tectum and tegmentum mesencephali, reticular formation, vagal and
      facial lobes and spinal cord. The cloning and characterization of this receptor
      provides an important tool to elucidate its participation in neuroendocrine and
      behavioural control.

PMID- 14713293
TI  - Neuronal-NOS adaptor protein expression after spreading depression: implications
      for NO production and ischemic tolerance.
AB  - Cortical spreading depression (CSD) is characterized by slowly propagating waves
      of neuronal/astrocytic depolarization and metabolic changes, followed by a period
      of quiescent neuronal and electroencephalographic activity. CSD acts as a
      preconditioning stimulus in brain, reducing cell death when elicited up to
      several days prior to an ischemic insult. Precise mechanisms associated with this
      neuroprotection are not known, although CSD increases the expression of a number
      of potentially neuroprotective genes/proteins. The nitric oxide (NO) system may
      be of particular importance, as it is acutely activated and chronically up
      regulated in cerebral cortex by CSD, and NO can ameliorate and exacerbate cell
      death under different conditions. Several molecules have recently been identified
      that modulate the production and/or cellular actions of NO, but it is not known
      whether their expression is altered by CSD. Therefore, the present study examined
      the effect of CSD on the spatiotemporal expression of PIN, CAPON, PSD-95, Mn-SOD
      and Cu/Zn-SOD mRNA in the rat brain. In situ hybridization using specific [35S]
      labelled oligonucleotides revealed that levels of PIN mRNA were significantly
      increased in the cortex and claustrum ( approximately 30-180%; p </= 0.01) after
      6 h and 1 and 2 days, but were again equivalent to contralateral (control)
      cortical values at 7, 14 and 28 days. CAPON mRNA levels were increased (
      approximately 30-180%; p </= 0.05) in the ipsilateral cortical hemisphere at 6 h
      and 2 days post treatment, but not at the other times examined. In contrast,
      levels of PSD-95, Mn- and Cu/Zn-SOD mRNA were not altered at any time after CSD.
      These results suggest that following CSD, nNOS activity and NO levels may be
      tightly regulated by both transcriptional and translational alterations in a
      range of nNOS adaptor proteins, which may contribute to CSD-induced
      neuroprotection against subsequent ischemia.

PMID- 14713294
TI  - Lactate and glucose as energy substrates during, and after, oxygen deprivation in
      rat hippocampal acute and cultured slices.
AB  - The effects of raised brain lactate levels on neuronal survival following hypoxia
      or ischemia is still a source of controversy among basic and clinical scientists.
      We have sought to address this controversy by studying the effects of glucose and
      lactate on neuronal survival in acute and cultured hippocampal slices. Following
      a 1-h hypoxic episode, neuronal survival in cultured hippocampal slices was
      significantly higher if glucose was present in the medium compared with lactate.
      However, when the energy substrate during the hypoxic period was glucose and then
      switched to lactate during the normoxic recovery period, the level of cell damage
      in the CA1 region of organotypic cultures was significantly improved from 64.3 +/
      2.1 to 74.6 +/- 2.1% compared with cultures receiving glucose during and after
      hypoxia. Extracellular field potentials recorded from the CA1 region of acute
      slices were abolished during oxygen deprivation for 20 min, but recovered almost
      fully to baseline levels with either glucose (82.6 +/- 10.0%) or lactate present
      in the reperfusion medium (108.1 +/- 8.3%). These results suggest that lactate
      alone cannot support neuronal survival during oxygen deprivation, but a
      combination of glucose followed by lactate provides for better neuroprotection
      than either substrate alone.

PMID- 14713295
TI  - Effect of methylphenidate on dopamine/DARPP signalling in adult, but not young,
      mice.
AB  - Methylphenidate (MPH), a dopamine uptake inhibitor, is the most commonly
      prescribed drug for the treatment of attention-deficit/hyperactivity disorder
      (ADHD) in children. We examined the effect of MPH on dopamine- and cAMP-regulated
      phosphoprotein, Mr 32 kDa (DARPP-32) phosphorylation at Thr34 (PKA-site) and
      Thr75 (Cdk5-site) using neostriatal slices from young (14-15- and 21-22-day-old)
      and adult (6-8-week-old) mice. MPH increased DARPP-32 Thr34 phosphorylation and
      decreased Thr75 phosphorylation in slices from adult mice. The effect of MPH was
      blocked by a dopamine D1 antagonist, SCH23390. In slices from young mice, MPH did
      not affect DARPP-32 phosphorylation. As with MPH, cocaine stimulated DARPP-32
      Thr34 phosphorylation in slices from adult, but not from young mice. In contrast,
      a dopamine D1 agonist, SKF81297, regulated DARPP-32 phosphorylation comparably in
      slices from young and adult mice, as did methamphetamine, a dopamine releaser.
      The results suggest that dopamine synthesis and the dopamine transporter are
      functional at dopaminergic terminals in young mice. In contrast, the lack of
      effect of MPH in young mice is likely attributable to immature development of the
      machinery that regulates vesicular dopamine release.

PMID- 14713296
TI  - RNA editing and alternative splicing of human serotonin 2C receptor in
      schizophrenia.
AB  - Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two
      different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events
      at five positions, which leads to amino acid substitutions that produce receptor
      variants with different pharmacological properties; (ii) 5-HT2CR mRNA is
      alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which
      encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies
      and the expression of the full-length and the truncated 5-HT2CR mRNA splice
      isoforms were analyzed in the prefrontal cortex of elderly subjects with
      schizophrenia vs. matched controls (ns = 15). No significant differences were
      found, indicating that there are no alterations in editing or alternative
      splicing of 5-HT2CRs that are associated with schizophrenia in persons treated
      with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA
      variants revealed that the expression of 5-HT2CR-tr was approximately 50% of that
      observed for the full-length isoform.

PMID- 14713297
TI  - Reduction of calcium release from the endoplasmic reticulum could only provide
      partial neuroprotection against beta-amyloid peptide toxicity.
AB  - Beta-amyloid (Abeta) peptide has been suggested to play important roles in the
      pathogenesis of Alzheimer's disease (AD). Abeta peptide neurotoxicity was shown
      to induce disturbance of cellular calcium homeostasis. However, whether
      modulation of calcium release from the endoplasmic reticulum (ER) can protect
      neurons from Abeta toxicity is not clearly defined. In the present study, Abeta
      peptide-triggered ER calcium release in primary cortical neurons in culture is
      modulated by Xestospongin C, 2-aminoethoxydiphenyl borate or FK506. Our results
      showed that reduction of ER calcium release can partially attenuate Abeta peptide
      neurotoxicity evaluated by LDH release, caspase-3 activity and quantification of
      apoptotic cells. While stress signals associated with perturbations of ER
      functions such as up-regulation of GRP78 was significantly attenuated, other
      signaling machinery such as activation of caspase-7 transmitting death signals
      from ER to other organelles could not be altered. We further provide evidence
      that molecular signaling in mitochondria play also a significant role in
      determining neuronal apoptosis because Abeta peptide-triggered activation of
      caspase-9 was not significantly reduced by attenuating ER calcium release. Our
      results suggest that neuroprotective strategies aiming at reducing Abeta toxicity
      should include molecular targets linked to ER perturbations associated with ER
      calcium release as well as mitochondrial stress.

PMID- 14713299
TI  - 4-Hydroxytamoxifen attenuates methamphetamine-induced nigrostriatal dopaminergic
      toxicity in intact and gonadetomized mice.
AB  - The present study was undertaken to assess the ability of 4-hydroxytamoxifen (4
      OHT) to alter methamphetamine-induced nigrostriatal dopaminergic toxicity. Three
      daily doses of 4-OHT (6 micro g/day) effectively attenuated methamphetamine
      induced nigrostriatal dopamine depletions in both sexes of intact and
      gonadectomized C57BL/6 J mice. 4-OHT alone did not alter the dopamine content
      levels in the striatum. Both male and female mice exhibited similar Cu, Zn
      superoxide dismutase protein levels in the striata whether after gonadectomy or 4
      OHT treatment. Furthermore, basal body temperature and methamphetamine-induced
      hyperthermia were not affected by 4-OHT treatment in either sex of mice. Using a
      lucigenen-derived chemiluminescence assay, we found that 4-OHT by itself can
      serve as a potent superoxide anion radical scavenger in vitro. The protective
      effects of 4-OHT against methamphetamine-induced nigrostriatal dopamine depletion
      can be, in part, due to its antioxidative characteristics. The free radical
      scavenging ability of 4-OHT calls for further investigations for its uses in
      clinical practice.

PMID- 14713298
TI  - Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase
      activation.
AB  - We describe here a new component of the phosphatidylinositol 3-kinase/Akt
      signaling pathway that directly impacts mitochondria. Akt (protein kinase B) was
      shown for the first time to be localized in mitochondria, where it was found to
      reside in the matrix and the inner and outer membranes, and the level of
      mitochondrial Akt was very dynamically regulated. Stimulation of a variety of
      cell types with insulin-like growth factor-1, insulin, or stress (induced by heat
      shock), induced translocation of Akt to the mitochondria within only several
      minutes of stimulation, causing increases of nearly eight- to 12-fold, and the
      mitochondrial Akt was in its phosphorylated, active state. Two mitochondrial
      proteins were identified to be phosphorylated following stimulation of
      mitochondrial Akt, the beta-subunit of ATP synthase and glycogen synthase kinase
      3beta. The finding that mitochondrial glycogen synthase kinase-3beta was rapidly
      and substantially modified by Ser9 phosphorylation, which inhibits its activity,
      following translocation of Akt to the mitochondria is the first evidence for a
      regulatory mechanism affecting mitochondrial glycogen synthase kinase-3beta.
      These results demonstrate that signals emanating from plasma membrane receptors
      or generated by stress rapidly modulate Akt and glycogen synthase kinase-3beta in
      mitochondria.

PMID- 14713300
TI  - Subunit composition and quantitative importance of GABA(A) receptor subtypes in
      the cerebellum of mouse and rat.
AB  - In cerebellum, 13 different GABA(A) receptor subunits are expressed. The number
      of different receptor subtypes formed in this tissue, their subunit composition
      and their quantitative importance so far has not been determined. In the present
      study, immunodepletion by immunoaffinity chromatography, as well as
      immunoprecipitation and western blot analysis was performed using 13 different
      subunit-specific antibodies to provide an overview on the subunit composition and
      abundance of GABA(A) receptor subtypes in mouse and rat cerebellum. Results
      obtained indicate that alpha1betaxgamma2, alpha1alpha6betaxgamma2,
      alpha6betaxgamma2, alpha6betaxdelta and alpha1alpha6betaxdelta are the major
      GABA(A) receptor subtypes present in the cerebellum. In addition, small amounts
      of alpha1betaxdelta receptors and a series of minor receptor subtypes containing
      alpha2, alpha3, alpha4, alpha5, gamma1 or gamma3 subunits are also present in the
      cerebellum. Whereas the abundance of alpha1alpha6betaxgamma2, alpha6betaxdelta
      and alpha1alpha6betaxdelta receptors is different in mouse and rat cerebellum,
      that of other receptors is quite similar in these tissues. Data obtained for the
      first time provide an overview on the GABA(A) receptor subtypes present in the
      cerebellum and represent the basis for further studies investigating changes in
      receptor expression and composition under pathological conditions.

PMID- 14713301
TI  - Selective prion protein binding to synaptic components is modulated by oxidative
      and nitrosative changes induced by copper(II) and peroxynitrite in cholinergic
      synaptosomes, unveiling a role for calcineurin B and thioredoxin.
AB  - Choline acetyltransferase (ChAT) and choline transport are decreased after
      nitrosative stress. ChAT activity is altered in scrapie-infected neurons, where
      oxidative stress develops. Cellular prion protein (PrPc) may play a
      neuroprotective function in participating in the redox control of neuronal
      environment and regulation of copper metabolism, a role impaired when PrPc is
      transformed into PrPSc in prion pathologies. The complex cross-talk between PrPc
      and cholinergic neurons was analyzed in vitro using peroxynitrite and Cu2+
      treatments on nerve endings isolated from Torpedo marmorata, a model of the
      motoneuron pre-synaptic element. Specific interactions between solubilized
      synaptic components and recombinant ovine prion protein (PrPrec) could be
      demonstrated by Biacore technology. Peroxynitrite abolished this interaction in a
      concentration-dependent way and induced significant alterations of neuronal
      targets. Interaction was restored by prior addition of peroxynitrite trapping
      agents. Cu2+ (in the form of CuSO4) treatment of synaptosomes triggered a milder
      oxidative effect leading to a bell-shaped increase of PrPrec binding to
      synaptosomal components, counteracted by the natural thiol agents, glutathione
      and thioredoxin. Copper(II)-induced modifications of thiols in several neuronal
      proteins. A positive correlation was observed between PrPrec binding and
      immunoreactive changes for calcineurin B and its partners, suggesting a synergy
      between calcineurin complex and PrP for copper regulation.

PMID- 14713302
TI  - The expression of brain cyclooxygenase-2 is down-regulated in the cytosolic
      phospholipase A2 knockout mouse.
AB  - We examined brain phospholipase A2 (PLA2) activity and the expression of enzymes
      metabolizing arachidonic acid (AA) in cytosolic PLA2 knockout () mice to see if
      other brain PLA2 can compensate for the absence of cPLA2 alpha and if cPLA2
      couples with specific downstream enzymes in the eicosanoid biosynthetic pathway.
      We found that the rate of formation of prostaglandin E2 (PGE2), an index of net
      cyclooxygenase (COX) activity, was decreased by 62% in the compared with the
      control mouse brain. The decrease was accompanied by a 50-60% decrease in mRNA
      and protein levels of COX-2, but no change in these levels in COX-1 or in PGE
      synthase. Brain 5-lipoxygenase (5-LO) and cytochrome P450 epoxygenase (cyp2C11)
      protein levels were also unaltered. Total and Ca2+-dependent PLA2 activities did
      not differ significantly between and control mice, and protein levels of type VI
      iPLA2 and type V sPLA2, normalized to actin, were unchanged. These results show
      that type V sPLA2 and type VI iPLA2 do not compensate for the loss of brain cPLA2
      alpha, and that this loss has significant downstream effects on COX-2 expression
      and PGE2 formation, sparing other AA oxidative enzymes. This suggests that cPLA2
      is critical for COX-2-derived eicosanoid production in mouse brain.

PMID- 14713303
TI  - Repeated cocaine administration changes the function and subcellular distribution
      of adenosine A1 receptor in the rat nucleus accumbens.
AB  - Adenosine A1 receptor (A1) protein and mRNA is increased in the nucleus accumbens
      following repeated cocaine treatment. In spite of this protein up-regulation, A1
      agonist-stimulated [35S]GTPgammaS binding was attenuated in accumbens homogenates
      of rats withdrawn for 3 weeks from 1 week of daily cocaine injections. Cellular
      subfractionation revealed that the discrepancy between total A1 protein and G
      protein coupling resulted from a smaller proportion of receptors in the plasma
      membrane. The decrease in functional receptor in the plasma membrane was further
      indicated by diminished formation of heteromeric receptor complex consisting of
      A1 and dopamine D1A receptors. To explore the functional significance of the
      altered distribution of A1 receptors, at 3 weeks after discontinuing repeated
      cocaine or saline, animals were injected with cocaine and 45 min later the
      subcellular distribution of A1 receptors quantified. Whereas a cocaine challenge
      in repeated saline-treated animals induced a marked increase in membrane
      localization of the A1 receptor, the relative distribution of receptors in
      repeated cocaine rats was not affected by acute cocaine. These data suggest that
      the sorting and recycling of A1 receptors is dysregulated in the nucleus
      accumbens as the consequence of repeated cocaine administration.

PMID- 14713304
TI  - Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1):
      cloning of the EAAT1 promoter and characterization of its basal and inducible
      activity in human astrocytes.
AB  - Excitatory amino acid transporter 1 (EAAT1) is one of the two glial glutamate
      transporters that clear the extracellular glutamate generated during neuronal
      signal transmission. Here, we cloned and characterized a 2.1-kb promoter region
      of human EAAT1 and investigated its function in the transcriptional regulation of
      the EAAT1 gene in human primary astrocytes. The full-length promoter region
      lacked TATA and CCAAT boxes and an initiator element, it contained several
      potential transcription factor-binding sites and it exhibited promoter activity
      in primary astrocytes and in several types of transformed cells. Consecutive 5'
      deletion analysis of the EAAT1 promoter indicated the presence of negative and
      positive regulatory regions and a putative core promoter between -57 bp and +20
      bp relative to the transcription start site (TSS). The core promoter contained a
      single GC-box in position -52/-39 and one E-box near the TSS and the GC-box site
      that was responsible for 90% of the basal promoter activity as determined by
      mutational analysis. Electrophoretic mobility shift, supershift and competition
      assays demonstrated binding of stimulating proteins (Sp) 1 and 3 to the GC-box
      and upstream stimulating factor (USF) 1 to the E-box. Treatment of primary human
      astrocytes with cellular modulators 8-bromo cyclic AMP and epidermal growth
      factor increased EAAT1 promoter activity in transient transfection assays and
      increased cellular EAAT1 mRNA expression and glutamate uptake by astrocytes.
      Conversely, tumor necrosis factor-alpha reduced both EAAT promoter activity and
      cellular EAAT1 mRNA expression. These results enable studies of transcriptional
      regulation of EAAT1 gene at the promoter level.

PMID- 14713305
TI  - Non-genomic modulation of dopamine release by bisphenol-A in PC12 cells.
AB  - An endocrine disruptor chemical, bisphenol-A (BPA), is reported to have several
      short-term actions in various tissues and/or cells; however, the mechanisms of
      these actions have not been fully elucidated. We investigated short-term actions
      evoked by BPA in pheochromocytoma PC12 cells. BPA elicited dopamine release in
      PC12 cells in a dose-dependent manner. A selective N-type calcium channel
      antagonist (omega-conotoxin GVIA) and a ryanodine receptor blocker (ryanodine)
      inhibited the BPA-induced dopamine release. The expression of ryanodine receptor
      mRNA was detected by RT-PCR in PC12 cells. Subsequently, in order to prove
      whether membrane receptors participate in BPA-evoked dopamine release, a guanine
      nucleotide-binding protein inhibitor [guanosine 5'-(beta-thio) diphosphate],
      cyclic AMP antagonist (Rp-cAMPS) or protein kinase A inhibitor (H7 or H89) was
      added to PC12 cells prior to BPA-treatment. All of these agents suppressed BPA
      evoked dopamine release, indicating that multiple signaling pathways may be
      involved in BPA-evoked dopamine release in PC12 cells. In conclusion, we
      demonstrated that BPA induced dopamine release in a non-genomic manner through
      guanine nucleotide-binding protein and N-type calcium channels. These findings
      illustrate a novel function of BPA and suggest that exposure to BPA influences
      the function of dopaminergic neurons.

PMID- 14713306
TI  - Enhancement of ischemia-induced tyrosine phosphorylation of Kv1.2 by vascular
      endothelial growth factor via activation of phosphatidylinositol 3-kinase.
AB  - Our studies observed that, consistent with the literature, ischemic/hypoxic
      insults increased the expression of voltage-gated potassium channel (Kv) 1.2
      potassium channel as well as elevating the endogenous level of vascular
      endothelial growth factor (VEGF) in neurons of adult rat brain following middle
      cerebral artery occlusion and in SH-SY5Y cells after hypoxia and glucose
      deprivation. Concomitantly, we also observed that ischemic injury increased the
      tyrosine phosphorylation of Kv 1.2 in in vivo and in vitro; the introduction of
      exogenous VEGF could attenuate cell death in in vitro models. Furthermore, we
      found that the protective effect of VEGF is mediated through its up-regulative
      actions on the tyrosine phosphorylation of Kv 1.2, which in turn has a direct
      influence on cell viability after ischemic insult. In substantiation of this
      result, we used anti-sense methodology to suppress the expression of endogenous
      VEGF, which significantly inhibited the tyrosine phosphorylation of Kv 1.2 and
      increased cell death elicited by ischemic/hypoxic injury. Finally, the
      enhancement of the tyrosine phosphorylation of the channel by VEGF in neuronal
      cells was significantly attenuated in the presence of wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase (PI3-K), or genestin, an inhibitor of tyrosine
      kinase, thus suggesting that the phosphorylation of Kv 1.2 induced by VEGF is
      mechanistically linked to the PI3-K pathway.

PMID- 14713307
TI  - Pharmacologic suppression of neuronal oxidative damage and dendritic degeneration
      following direct activation of glial innate immunity in mouse cerebrum.
AB  - Activation of glial innate immunity is widely proposed to contribute to a number
      of degenerative and destructive diseases of brain. However, the precise role of
      activated innate immunity has been difficult to define in vivo because of
      multiple simultaneous pathogenic processes and responses to injury that confound
      interpretation of results from complex models of disease. Here, we used the model
      of intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) to test
      the hypothesis that directly activated glial innate immunity leads to
      neurodegeneration in cerebrum and to establish the molecular determinants of and
      neuroprotectants from such innate immunity-mediated neuronal damage. Our results
      showed that ICV LPS induced delayed, reversible oxidative damage to cerebral
      neuronal membranes as measured by F4-neuroprostanes that was coincident with
      degeneration of the hippocampal pyramidal neuron dendritic system, but not neuron
      death, in adult mice. Both neuronal oxidative damage and dendritic degeneration
      were NF-kappaB and iNOS dependent and were completely suppressed by ibuprofen and
      alpha-tocopherol, but not naproxen or gamma-tocopherol. These results prove that
      activation of glial innate immunity can lead to neurodegeneration independent of
      other pathologic processes, closely associate oxidative damage to neuronal
      membranes with degeneration of the dendritic system, and provide a possible
      explanation for the varying efficacy of neuroprotectants that have been suggested
      in observational studies of dementia.

PMID- 14713308
TI  - Over-expression of antioxidant enzymes protects cultured hippocampal and cortical
      neurons from necrotic insults.
AB  - There is now considerable knowledge concerning neuron death following necrotic
      insults, and it is believed that the generation of reactive oxygen species (ROS)
      and oxidative damage play a pivotal role in the neuron death. Prompted by this,
      we have generated herpes simplex virus-1 amplicon vectors over-expressing the
      genes for the antioxidant enzymes catalase (CAT) or glutathione peroxidase (GPX),
      both of which catalyze the degradation of hydrogen peroxide. Over-expression of
      each of these genes in primary hippocampal or cortical cultures resulted in
      increased enzymatic activity of the cognate protein. Moreover, each enzyme
      potently decreased the neurotoxicity induced by kainic acid, glutamate, sodium
      cyanide and oxygen/glucose deprivation. Finally, these protective effects were
      accompanied by parallel decreases in hydrogen peroxide accumulation and the
      extent of lipid peroxidation. These studies not only underline the key role
      played by ROS in the neurotoxicity of necrotic insults, but also suggest
      potential gene therapy approaches.

PMID- 14713309
TI  - Ceramide pathways modulate ethanol-induced cell death in astrocytes.
AB  - We showed previously that alcohol exposure during in vivo brain development
      induced astroglial damage and caused cell death. Because ceramide modulates a
      number of biochemical and cellular responses to stress, including apoptosis, we
      now investigate whether ethanol-induced cell death in astrocytes is mediated by
      ceramide signalling pathways triggering apoptosis. Here we show that both ethanol
      and ceramide are able to induce apoptotic death in cultured astrocytes, in a dose
      dependent manner, and that C2-ceramide addition potentiates the apoptotic effects
      of ethanol. Cell death induced by ethanol is associated with stimulation of
      neutral and acidic sphingomyelinase (SMase) and ceramide generation, as well as
      with activation of stress-related kinases, c-Jun N-terminal kinase (JNK), p38
      mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase
      (ERK) pathways. We also provide evidence for the participation of JNK and p38 in
      ethanol-induced cell death, because pharmacological inhibitors of these kinases
      largely prevent the apoptosis induced by ethanol or by ethanol and C2-ceramide.
      Furthermore, we show that ethanol-induced ERK activation triggers the stimulation
      of cyclo-oxygenase-2 (COX-2) and the release of prostaglandin E2, and that
      blockade of the mitogen-activated protein kinase kinase (MEK)/ERK pathway by
      PD98059 abolishes the up-regulation of COX-2 induced by ethanol plus ceramide,
      and decreases the ethanol-induced apoptosis. These results strongly suggest that
      ethanol is able to stimulate the SMase-ceramide pathway, leading to the
      activation of signalling pathways implicated in cell death. These findings
      provide an insight into the mechanisms involved in ethanol-induced astroglial
      cell death during brain development.

PMID- 14713310
TI  - Repeated amphetamine treatment induces neurite outgrowth and enhanced amphetamine
      stimulated dopamine release in rat pheochromocytoma cells (PC12 cells) via a
      protein kinase C- and mitogen activated protein kinase-dependent mechanism.
AB  - Repeated intermittent treatment with amphetamine (AMPH) induces both neurite
      outgrowth and enhanced AMPH-stimulated dopamine (DA) release in PC12 cells. We
      investigated the role of protein kinases in the induction of these AMPH-mediated
      events by using inhibitors of protein kinase C (PKC), mitogen activated protein
      kinase (MAP kinase) or protein kinase A (PKA). PKC inhibitors chelerythrine (100
      nm and 300 nm), Ro31-8220 (300 nm) and the MAP kinase kinase inhibitor, PD98059
      (30 micro m) inhibited the ability of AMPH to elicit both neurite outgrowth and
      the enhanced AMPH-stimulated DA release. The direct-acting PKC activator, 12-O
      tetradecanoyl phorbol 13-acetate (TPA, 250 nm) mimicked the ability of AMPH to
      elicit neurite outgrowth and enhanced DA release. On the contrary, a selective
      PKA inhibitor, 100 micro m Rp-8-Br-cAMPS, blocked only the development of AMPH
      stimulated DA release but not the neurite outgrowth. Treatment of the cells with
      acute AMPH elicited an increase in the activity of PKC and MAP kinase but not
      PKA. These results demonstrated that AMPH-induced increases in MAP kinase and PKC
      are important for induction of both the enhancement in transporter-mediated DA
      release and neurite outgrowth but PKA was only required for the enhancement in
      AMPH-stimulated DA release. Therefore the mechanisms by which AMPH induces
      neurite outgrowth and the enhancement in AMPH-stimulated DA release can be
      differentiated.

PMID- 14713311
TI  - A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease,
      confers reduced protein stability and impairs homo-oligomerization.
AB  - The identification of genetic mutations responsible for rare familial forms of
      Parkinson's disease (PD) have provided tremendous insight into the molecular
      pathogenesis of this disorder. Mutations in the DJ-1 gene cause autosomal
      recessive early onset PD in two European families. A Dutch kindred displays a
      large homozygous genomic deletion encompassing exons 1-5 of the DJ-1 gene,
      whereas an Italian kindred harbors a single homozygous L166P missense mutation. A
      homozygous M26I missense mutation was also recently reported in an Ashkenazi
      Jewish patient with early onset PD. Mutations in DJ-1 are predicted to be loss of
      function. The recent determination of the crystal structure of human DJ-1
      demonstrates that it exists in a homo-dimeric form in vitro, whereas the L166P
      mutant exists only as a monomer. Here, we examine the in vivo effects of the
      pathogenic L166P and M26I mutations on the properties of DJ-1 in cell culture. We
      report that the L166P mutation confers markedly reduced protein stability to DJ
      1, which results from enhanced degradation by the 20S/26S proteasome but not from
      a loss of mRNA expression. Furthermore, the L166P mutant protein exhibits an
      impaired ability to self-interact to form homo-oligomers. In contrast, the M26I
      mutation does not appear to adversely affect either protein stability, turnover
      by the proteasome, or the capacity of DJ-1 to form homo-oligomers. These
      properties of the L166P mutation may contribute to the loss of normal DJ-1
      function and are likely to be the underlying cause of early onset PD in affected
      members of the Italian kindred.

PMID- 14713314
TI  - Restricted changes in major surface protein-2 (msp2) transcription after
      prolonged in vitro passage of Anaplasma phagocytophilum.
AB  - BACKGROUND: Anaplasma phagocytophilum strains often vary in Msp2 expression, a
      situation assumed to be related to immune evasion. However, Msp2 is also an
      adhesin, and little is known about the role of endogenous msp2 transcriptional
      changes in the absence of immune selection. Thus, Msp2 profiles and msp2
      transcripts of low passage A. phagocytophilum Webster strain, initially comprised
      of a single abundant msp2 transcript, were re-examined after > or = 20 in vitro
      passages without immune selection. RESULTS: Using an Msp2 monoclonal antibody,
      immunoblots revealed an unchanged dominant band and several weak bands that
      appeared with passage. Similarly, msp2 transcript diversity changed, with a
      decrease in the initially abundant low passage transcript and appearance of a
      newly abundant and several minor msp2 transcripts with high passage. BLASTN
      search of the A. phagocytophilum HZ strain genome revealed > or = 52 msp2
      paralogs. CONCLUSIONS: Msp2 expression and msp2 transcription modulate even
      without immune selective pressures. However, the limited diversity of msp2
      transcripts in the absence of immune pressure suggests selection for Msp2 by
      specific functions beyond that of immune evasion, in spite of a large genomic
      reservoir for Msp2 diversity.

PMID- 14713315
TI  - The MacNew Heart Disease health-related quality of life instrument: a summary.
AB  - BACKGROUND: The measurement of health, the effects of disease, and the impact of
      health care include not only an indication of changes in disease frequency and
      severity but also an estimate of patients' perception of health status before and
      after treatment. One of the more important developments in health care in the
      past decade may be the recognition that the patient's perspective is as
      legitimate and valid as the clinician's in monitoring health care outcomes. This
      has lead to the development of instruments to quantify the patients' perception
      of their health status before and after treatment. METHODS: We review evidence
      supporting the measurement properties of the MacNew Heart Disease Health-related
      Quality of Life [MacNew] Questionnaire which was designed to evaluate how daily
      activities and physical, emotional, and social functioning are affected by
      coronary heart disease and its treatment. RESULTS: Reliability was demonstrated
      by using internal consistency and the intraclass correlation coefficients for the
      three domains in the Dutch, English, Farsi, German, and Spanish versions of the
      MacNew. With internal consistency and intraclass correlation coefficients =>0.73,
      reliability is high. Validity of the MacNew was examined with factor analysis and
      three core underlying factors, physical, emotional, and social, were identified,
      explaining 63.0 - 66.5% of the observed variance and replicated in the
      translations with psychometric data. Construct validity of the MacNew was further
      demonstrated by extensive substantiation of the logical relationships, defined a
      priori, between items and other comparison tools. The MacNew is responsive and
      sensitive to changes in HRQL following various interventions for patients with
      heart disease with 11 of 13 effect size statistics >0.80. Taking an average of 10
      minutes or less to complete, the respondent-burden for the MacNew is low and its
      acceptability is demonstrated by response rates of over 90%. Normative data are
      available for patients with myocardial infarction, angina, and heart failure in
      the English version. CONCLUSION: The MacNew may be a valuable tool for assessing
      and evaluating health related quality of life in patients with heart disease.

PMID- 14713316
TI  - Health-related quality of life outcomes after kidney transplantation.
AB  - With the improvements in short and long term graft and patient survival after
      renal transplantation over the last two decades Health-Related Quality of Life
      (HRQL) is becoming an important additional outcome parameter. Global and disease
      specific instruments are available to evaluate objective and subjective QOL.
      Among the most popular global tools is the SF-36, examples of disease specific
      instruments are the Kidney Transplant Questionnaire (KTQ), the Kidney Disease
      Questionnaire (KDQ) and the Kidney Disease-Quality of Life (KDQOL). It is
      generally accepted that HRQL improves dramatically after successful renal
      transplantation compared to patients maintained on dialysis treatment but listed
      for a transplant. It is less clear however which immunosuppressive regimen
      confers the best QOL. Only few studies compared the different regimens in terms
      of QOL outcomes. Although limited in number, these studies seem to favour non
      cyclosporine based protocols. The main differences that could be observed between
      patients on cyclosporine versus tacrolimus or sirolimus therapy concern the
      domains of appearance and fatigue. This may be explained by two common adverse
      effects occurring under cyclosporine therapy, gingival hyperplasia and hair
      growth. Another more frequently occurring side effect under calcineurin inhibitor
      therapy is tremor, which may favour CNI free protocols. This hypothesis, however,
      has not been formally evaluated in a randomised trial using HRQL measurements.In
      summary HRQL is becoming more of an issue after renal transplantation. Whether a
      specific immunosuppressive protocol is superior to others in terms of HRQL
      remains to be determined.

PMID- 14713318
TI  - Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone
      sulbactam against Acinetobacter baumannii strains in terms of bactericidal
      efficacy and resistance selection.
AB  - BACKGROUND: We compared imipenem, meropenem and cefoperazone-sulbactam against
      hospital originated A. baumannii strains in terms of bactericidal efficacy and
      selection of resistant mutants during treatment in a rat thigh abscess model.
      METHODS: A total of 18 strains were inoculated in 54 animals (one strain for
      three animals). Randomly selected 10 among these 18 strains were inoculated in
      another 10 rats as the control group. Imipenem, meropenem and cefoperazone
      sulbactam were the antibiotics compared. After four days of treatment, Wistar
      albino rats (200 to 250 g) were sacrificed and the abscess materials were
      processed for mean colony counts and for the presence of resistant mutants.
      RESULTS: The mean CFUs per gram (mean +/- (std. deviation) [x10(4)]) of the
      abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17),
      meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The
      differences were not significant. On the other hand, no resistant mutant was
      detected in abscess materials. CONCLUSION: This study indicated; first,
      cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in
      this particular abscess model and second, emergence of resistance due to
      spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

PMID- 14713317
TI  - Self-administration and interviewer-administration of the German Chronic
      Respiratory Questionnaire: instrument development and assessment of validity and
      reliability in two randomised studies.
AB  - BACKGROUND: Assessment of health-related quality of life (HRQL) is important in
      patients with chronic obstructive pulmonary disease (COPD). Despite the high
      prevalence of COPD in Germany, Switzerland and Austria there is no validated
      disease-specific instrument available. The objective of this study was to
      translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely
      used respiratory HRQL questionnaires, into German, develop an interviewer- and
      self-administered version including both standardised and individualised dyspnoea
      questions, and validate these versions in two randomised studies. METHODS: We
      recruited three groups of patients with COPD in Switzerland, Germany and Austria.
      The 44 patients of the first group completed the CRQ during pilot testing to
      adapt the CRQ to German-speaking patients. We then recruited 80 patients
      participating in pulmonary rehabilitation programs to assess internal consistency
      reliability and cross-sectional validity of the CRQ. The third group consisted of
      38 patients with stable COPD without an intervention to assess test-retest
      reliability. To compare the interviewer- and self-administered versions, we
      randomised patients in groups 2 and 3 to the interviewer- or self-administered
      CRQ. Patients completed both the standardised and individualised dyspnoea
      questions. RESULTS: For both administration formats and all domains, we found
      good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89).
      Cross-sectional validity tended to be better for the standardised compared to the
      individualised dyspnoea questions and cross-sectional validity was slightly
      better for the self-administered format. Test-retest reliability was good for
      both the interviewer-administered CRQ (intraclass correlation coefficients for
      different domains between 0.81 and 0.95) and the self-administered format
      (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person
      variability was responsible for the higher test-retest reliability of the
      interviewer-administered format while between person variability was similar for
      both formats. CONCLUSIONS: Investigators in German-speaking countries can choose
      between valid and reliable self-and interviewer-administered CRQ formats.

PMID- 14713319
TI  - Tracking the implementation of NCCLS M100-S12 expanded-spectrum cephalosporin MIC
      breakpoints for nonmeningeal isolates of Streptococcus pneumoniae by clinical
      laboratories in the United States during 2002 and 2003.
AB  - BACKGROUND: The Performance Standards for Antimicrobial Susceptibility Testing,
      Twelfth Informational Supplement, M100-S12, published by the National Committee
      for Clinical Laboratory Standards (NCCLS) in January 2002 introduced distinct
      minimum inhibitory concentration (MIC) interpretative breakpoints for
      ceftriaxone, cefotaxime, and cefepime for nonmeningeal isolates of Streptococcus
      pneumoniae. Previously, a single set of interpretative breakpoints was used for
      both meningeal and nonmeningeal isolates. METHODS: To estimate the rate of
      adoption of the M100-S12 interpretive breakpoints by clinical laboratories,
      antimicrobial susceptibility test results for ceftriaxone and cefotaxime from
      nonmeningeal S. pneumoniae isolates were studied using data collected from
      January 2002 to June 2003 by The Surveillance Network Database--USA (TSN, an
      electronic surveillance database. RESULTS: Of the 262 laboratories that provided
      data that could be evaluated, 67.6% had adopted the M100-S12 breakpoints one and
      one-half years after they were published. CONCLUSIONS: The NCCLS M100-S12
      recommendation to interpret MICs to expanded-spectrum cephalosporins using two
      distinct sets of breakpoints for meningeal and nonmeningeal isolates of S.
      pneumoniae was steadily implemented by clinical microbiology laboratories in the
      United States following their initial publication in January 2002. The use of
      these new breakpoints more accurately reflects the clinical activities of
      expanded-spectrum cephalosporins than did the single set of interpretative
      breakpoints previously used for both meningeal and nonmeningeal isolates.

PMID- 14713320
TI  - Learning from the problems of problem-based learning.
AB  - BACKGROUND: The last decade has witnessed a rapid expansion of biomedical
      knowledge. Despite this, fashions in medical education over the same period have
      shifted away from factual (didactic) teaching and towards contextual, or problem
      based, learning (PBL). This paradigm shift has been justified by studies showing
      that PBL improves reasoning and communication while being associated with few if
      any detectable knowledge deficits. DISCUSSION: Analysis of the literature
      indicates that the recent rapid rise of PBL has closely paralleled the timing of
      the information explosion. The growing dominance of PBL could thus worsen the
      problems of information management in medical education via several mechanisms:
      first, by creating the impression that a defined spectrum of core factual
      knowledge suffices for clinical competence despite ongoing knowledge expansion
      (quality cost); second, by dissuading teachers from refining the educational
      utility of didactic modalities (improvement cost); and third, by reducing faculty
      time for developing reusable resources to impart factual knowledge more
      efficiently (opportunity cost). SUMMARY: These costs of PBL imply a need for
      strengthening the knowledge base of 21st-century medical graduates. New
      initiatives towards this end could include the development of more integrated
      cognitive techniques for facilitating the comprehension of complex data; the
      design of differentiated medical curricula for producing graduates with defined
      high-priority skill sets; and the encouragement of more cost-effective faculty
      teaching activities focused on the prototyping and testing of innovative
      commercializable educational tools.

PMID- 14713321
TI  - Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne
      muscular dystrophy: a case report.
AB  - BACKGROUND: Clinical characteristics and complications of Duchenne muscular
      dystrophy caused by skeletal and cardiac muscle degeneration are well known.
      Gastro-intestinal involvement has also been recognised in these patients. However
      an acute perforated gastro-duodenal peptic ulcer has not been documented up to
      now. CASE PRESENTATION: A 26-year-old male with Duchenne muscular dystrophy with
      a clinical and radiographic diagnosis of acute perforated gastro-duodenal peptic
      ulcer is treated non-operatively with naso-gastric suction and intravenous
      medication. Gastrointestinal involvement in Duchenne muscular dystrophy and
      therapeutic considerations in a high risk patient are discussed. CONCLUSION: Non
      surgical treatment for perforated gastro-duodenal peptic ulcer should be
      considered in high risk patients, as is the case in patients with Duchenne
      muscular dystrophy. Patients must be carefully observed and operated on if non
      operative treatment is unsuccessful.

PMID- 14713323
TI  - Insulin and cancer.
AB  - Obesity has recently been linked to mortality from the majority of cancers. The
      insulin/insulin-like growth factor (IGF) system may partly explain this effect.
      The metabolic syndrome, associated with hyperinsulinemia, may modulate this
      effect. Recent evidence supports the role of insulin and IGF-1 as important
      growth factors, acting through the tyrosine kinase growth factor cascade in
      enhancing tumor cell proliferation. In addition, the metabolic syndrome
      associated with a chronic inflammatory state and accompanying cytokine
      abnormalities may also contribute to tumor progression. Growing links between
      insulin and the etiology as well as prognosis in colon, prostate, pancreatic,
      and, particularly, breast cancer are reviewed. Of particular concern is the
      evidence that elevated IGF-1 may interfere with cancer therapy, adversely
      affecting prognosis. The role of insulin is of concern because of the increasing
      levels of obesity and the associated metabolic syndrome. Weight gain, through
      typical Western diet; limited levels of activity; and, more recently, stress
      related changes in neuroendocrine function may lead to insulin resistance and
      hyperinsulinemia. The opportunity for a multidisciplinary approach involving
      nutrition, exercise, and stress reduction in an integrative setting may be
      crucial to limiting the insulin-resistant state and improving cancer outcomes.

PMID- 14713325
TI  - Therapeutic massage and healing touch improve symptoms in cancer.
AB  - Complementary therapies are increasingly used to reduce side effects of cancer
      treatment, without evidence for their effectiveness. In a randomized,
      prospective, 2-period, crossover intervention study, the authors tested the
      effects of therapeutic massage (MT) and healing touch (HT), in comparison to
      presence alone or standard care, in inducing relaxation and reducing symptoms in
      230 subjects. MT and HT lowered blood pressure, respiratory rate (RR), and heart
      rate (HR). MT lowered anxiety and HT lowered fatigue, and both lowered total mood
      disturbance. Pain ratings were lower after MT and HT, with 4-week nonsteroidal
      antiinflammatory drug use less during MT. There were no effects on nausea.
      Presence reduced RR and HR but did not differ from standard care on any measure
      of pain, nausea, mood states, anxiety, or fatigue. MT and HT are more effective
      than presence alone or standard care in reducing pain, mood disturbance, and
      fatigue in patients receiving cancer chemotherapy.

PMID- 14713326
TI  - Mistletoe and gemcitabine in patients with advanced cancer: a model for the phase
      I study of botanicals and botanical-drug interactions in cancer therapy.
AB  - Plant extracts of the European mistletoe (MTE), Viscum album, the most widely
      used cancer treatment in Germany, have been used in European countries as sole
      intervention or as adjunct to conventional cancer therapies for more than 80
      years. Preclinical data suggest immunostimulatory and cytotoxic effects of MTE.
      While the clinical efficacy of MTE in cancer is being investigated, toxicity and
      potential interactions of MTE with standard chemotherapeutic agents are unknown.
      Gemcitabine is an approved antimetabolite chemotherapeutic agent effective as
      single agent in patients with solid tumors (ST). The documented metabolism and
      pharmacokinetics of gemcitabine make this agent well suited for the study of
      botanical-chemotherapy drug interactions (BDIA) in cancer. Based on reports of
      altered drug metabolism associated with botanical preparations, research into
      BDIA has intensified. The phase I, 2-stage, dose-escalation study outlined here
      will test MTE with gemcitabine as a paradigm for the phase I investigation of
      botanical-drug combination treatments in patients with advanced ST. The protocol
      including the following components has been reviewed and approved by the National
      Cancer Institute Institutional Review Board (IRB), the National Naval Medical
      Center IRB, and the Navy Clinical Investigation Program (study 02-074): (1) use
      of a standardized MTE, approved by the Food and Drug Administration for
      investigational use; (2) independent verification of key MTE components
      considered biologically active; (3) identification of contaminants and
      adulterants; (4) pharmacokinetics of gemcitabine and its principal metabolites
      before and upon exposure to MTE; (5) safety and toxicity data collection; (6)
      assays of plasma ML antibody production in vivo; and (7) pharmacodynamic studies
      of the botanical-drug combination.

PMID- 14713327
TI  - Oncology nursing and integrative care: a new way of being.
AB  - Oncology nursing is a long-established specialty in the practice of professional
      nursing. The paradigm shift to a more holistic perspective in health care is
      affecting not only the delivery of care but also the beliefs and value of nurses
      who work with people experiencing cancer. This article will examine the role of
      holistic theory and complementary therapies as innovations in nursing education
      and nursing practice. Suggestions for assessing and planning for an integrative
      approach to intervention will be discussed. Outcomes from a senior nursing
      student survey concerning the integration of holistic nursing and complementary
      therapies will be described. The future offers many challenges for professional
      nursing as a major player in today's health care system.

PMID- 14713328
TI  - Ganoderma lucidum (Reishi) in cancer treatment.
AB  - The popular edible mushroom Ganoderma lucidum (Reishi) has been widely used for
      the general promotion of health and longevity in Asian countries. The dried
      powder of Ganoderma lucidum was popular as a cancer chemotherapy agent in ancient
      China. The authors recently demonstrated that Ganoderma lucidum inhibits
      constitutively active transcription factors nuclear factor kappa B (NF-kappaB)
      and AP-1, which resulted in the inhibition of expression of urokinase-type
      plasminogen activator (uPA) and its receptor uPAR. Ganoderma lucidum also
      suppressed cell adhesion and cell migration of highly invasive breast and
      prostate cancer cells, suggesting its potency to reduce tumor invasiveness. Thus,
      Ganoderma lucidum clearly demonstrates anticancer activity in experiments with
      cancer cells and has possible therapeutic potential as a dietary supplement for
      an alternative therapy for breast and prostate cancer. However, because of the
      availability of Ganoderma lucidum from different sources, it is advisable to test
      its biologic activity.

PMID- 14713329
TI  - The integration of hypnosis into a model of palliative care.
AB  - There exists a need for a broad and inclusive model of integration of mind-body
      interventions for palliative care. Symptoms relating to psychological distress
      and existential concerns are even more prevalent than pain and other physical
      symptoms among those with life-limiting conditions. The hypnotic model's purpose
      is to improve the patient's total psychological, social, and spiritual well
      being. A 4-stage model of interventions is offered to assist the clinician in
      developing and implementing appropriate hypnotherapeutic treatment for
      noncurative patients. The focus of the hypnotherapy is to ameliorate the effects
      of pain and dyspnea to restore a level of psychological and physical wellbeing.
      Within this model of therapy for patients with active, progressive, far-advanced
      disease and a short life expectancy, the goals of the hypnotic intervention are
      to provide relief from pain and shortness of breath. Other focuses include
      assisting the patient with the psychological adjustment to their noncurative and
      ultimately final state.

PMID- 14713330
TI  - Patient responses to Cytoluminescent Therapy for cancer: an investigative report
      of early experiences and adverse effects of an unconventional form of
      photodynamic therapy.
AB  - Cytoluminescent Therapy (CLT) is an unconventional form of photodynamic therapy
      (PDT), utilizing a second-generation chlorophyll-derived photosensitizing agent
      and whole-body illumination. Starting in late 2002, CLT was administered in
      Ireland to 48 patients. Illumination with lasers and light-emitting diodes
      followed the administration of an initial bolus i.v. After returning home,
      patients continued self-administered treatment using oral agent activated by
      infrared lamps. CLT proponents claimed that these procedures were beneficial to
      patients with advanced cancer. An organization devoted to making information on
      alternative therapies available to the public was engaged to contact these CLT
      patients and assess the outcome. In informal contacts, patients reported that
      initial side effects were generally mild and transient. However, especially after
      commencing self-treatment, many reported unanticipated effects, including fatigue
      and general weakness, increased pain, cough, dyspnea, diminished appetite and
      weight loss, tissue necrosis, and other major symptoms. At a minimum of 6 months
      after initial CLT, no patient has reported an objective response, and some have
      complained of deterioration on the home treatment. There have been 17 deaths
      among the 48, with a mean survival after initial treatment among decedents of 4.2
      months. CLT, in this group, was a qualified failure, with a high incidence of
      aftereffects. The mode of action of these aftereffects has yet to be explored. In
      the future, CLT should be administered to patients only in carefully managed
      medical facilities, by fully trained and licensed professionals, under the
      supervision of relevant regulatory agencies, and with meticulous follow-up care.

PMID- 14713331
TI  - A novel hypothesis for thalidomide-induced limb teratogenesis: redox
      misregulation of the NF-kappaB pathway.
AB  - Several hypotheses have been proposed to explain the mechanisms of thalidomide
      teratogenesis, although none adequately accounts for the observed malformations
      and explains the basis for species specificity. Recent observations that
      thalidomide increases the production of free radicals and elicits oxidative
      stress, coupled with new insights into the redox regulation of nuclear
      transcription factors, lead to the suggestion that thalidomide may act through
      redox misregulation of the limb outgrowth pathways. Oxidative stress, as marked
      by glutathione depletion/oxidation and a shift in intracellular redox potential
      toward the positive, occurs preferentially in limbs of thalidomide-sensitive
      rabbits, but not in resistant rats. DNA binding of nuclear factor kappa-B (NF
      kappaB), a redox-sensitive transcription factor and key regulator of limb
      outgrowth, was shown to be significantly attenuated in rabbit limb cells and
      could be restored following the addition of a free radical spin-trapping agent,
      phenyl N-tert-butyl nitrone. The inability of NF-kappaB to bind to its DNA
      promoter results in the failure of limb cells to express fibroblast growth factor
      (FGF)-10 and twist in the limb progress zone (PZ) mesenchyme, which in turn
      attenuates expression of FGF-8 in the apical ectodermal ridge (AER). Failure to
      establish an FGF-10/FGF-8 feedback loop between the PZ and AER results in the
      truncation of limb outgrowth. We hypothesize that species-selective alterations
      in redox microenvironment caused by free radical production from thalidomide
      results in attenuation of the NF-kappaB-mediated gene expression that is
      responsible for limb outgrowth.

PMID- 14713332
TI  - Thioredoxin as a key molecule in redox signaling.

PMID- 14713333
TI  - Immunohistochemical evaluation of oxidative stress markers in chronic hepatitis
      C.
AB  - Oxidative stress (OS) plays a major role in chronic hepatitis C. Various OS
      markers have been found to be elevated in hepatitis C virus (HCV)-related liver
      disease. This study detected the presence of OS in serum and liver biopsy
      specimens of HCV patients. Reactive oxygen molecules (ROM) in sera of 54 HCV
      patients were compared with 23 controls. OS markers 8-hydroxydeoxyguanosine (8
      OHdG), 4-hydroxy-2-nonenal, malondialdehyde, and thioredoxin were measured in
      liver biopsy specimens of 18 HCV patients with fibrosis staging F1 (six); F2
      (two), F3 (four), and F4 (six). The interferon (IFN) response and hepatocellular
      carcinoma (HCC) occurrence in the presence of OS markers were also evaluated. The
      level of ROM in HCV patients was 318 +/- 56.7 Carr compared with 248 +/- 40.8
      Carr in controls (p=0.032). Multivariate analysis found age (p=0.0236) to be the
      only independent variable associated with increase in ROM in sera. In liver
      biopsy specimens, OS markers were found mainly around the area of piecemeal
      necrosis or the periportal area. The presence of OS markers seemed to increase
      with fibrosis staging, although not significantly. The OS DNA damage marker 8
      OHdG was detected in the nucleus of hepatocytes. Thirteen patients received IFN
      therapy. During the 4-year follow-up period, HCC developed in four nonresponders
      to IFN and in one untreated patient. OS markers were stained in both HCC cells
      and non-HCC cells in HCC patients. OS markers were found in serum and liver
      specimens of HCV-associated liver disease and in HCC tissue. Detection of OS
      markers may be important for monitoring disease progression in HCV patients.
      Antioxidant therapy in combination with antiviral therapy may minimize liver
      damage and aid in the prevention and subsequent development of HCC.

PMID- 14713334
TI  - The mammalian testis-specific thioredoxin system.
AB  - Redox control of cell physiology is one of the most important regulatory
      mechanisms in all living organisms. The thioredoxin system, composed of
      thioredoxin and thioredoxin reductase, has emerged as a key player in cellular
      redox-mediated reactions. For many years, only one thioredoxin system had been
      described in higher organisms, ubiquitously expressed in the cytoplasm of
      eukaryotic cells. However, during the last decade, we and others have identified
      and characterized novel thioredoxin systems with unique properties, such as
      organelle-specific localization in mitochondria or endoplasmic reticulum, tissue
      specific distribution mostly in the testis, and features novel for thioredoxins,
      such as microtubule-binding properties. In this review, we will focus on the
      mammalian testis-specific thioredoxin system that comprises three thioredoxins
      exclusively expressed in spermatids (named Sptrx-1, Sptrx-2, and Sptrx-3) and an
      additional thioredoxin highly expressed in testis, but also present in lung and
      other ciliated tissues (Txl-2). The implications of these findings in the context
      of male fertility and testicular cancer, as well as evolutionary aspects, will be
      discussed.

PMID- 14713335
TI  - Truncated thioredoxin: physiological functions and mechanism.
AB  - Human cytosolic thioredoxin (Trx), which is the 12-kDa protein disulfide
      reductase with the Cys-Gly-Pro-Cys active site and a key component of cellular
      redox biochemistry and regulation, acts as cocytokine upon leaderless secretion.
      A 10-kDa C-terminally truncated thioredoxin (Trx80) comprising the 80 or 84 N
      terminal amino acids is also secreted and present in plasma, where it originally
      was purified and identified as eosinophilic cytotoxicity enhancing factor.
      Recombinant Trx80 was discovered to be a potent mitogenic cytokine that
      stimulates growth of resting human peripheral blood mononuclear cells (PBMC) in a
      synthetic medium, an effect that Trx lacks. Trx80 is very different from Trx
      because it is a dimer lacking reductase activity and the cytokine activity is not
      dependent on the Cys residues of the Trx active-site motif. The primary targets
      of Trx80 in PBMC are monocytes that are activated to proliferate and increase
      expression of CD14, CD40, CD54, and CD86. Trx80 induces secretion of interleukin
      (IL)-12 in CD40+ monocytes from PBMC. Trx80 and IL-2 together were strongly
      synergistic to induce secretion of interferon-gamma in PBMC. Trx80 is a potent
      cytokine for monocytes directing the immune system to a Th1 response via IL-12
      production.

PMID- 14713336
TI  - Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a
      simple thioredoxin backup system.
AB  - Most cells contain high levels of glutathione and multiple glutaredoxins, which
      utilize the reducing power of glutathione to catalyze disulfide reductions in the
      presence of NADPH and glutathione reductase (the glutaredoxin system).
      Glutaredoxins, like thioredoxins, may operate as dithiol reductants and are
      involved as alternative pathways in cellular functions such as formation of
      deoxyribonucleotides for DNA synthesis (by reducing the essential enzyme
      ribonucleotide reductase), the generation of reduced sulfur (via 3'
      phosphoadenylylsulfate reductase), signal transduction, and the defense against
      oxidative stress. The three dithiol glutaredoxins of E. coli with the active-site
      sequence CPYC and a glutathione binding site in a thioredoxin/glutaredoxin fold
      display surprisingly different properties. These include the inducible OxyR
      regulated 10-kDa Grx1 or the highly abundant 24-kDa glutathione S-transferase
      like Grx2 (with Grx3 it accounts for 1% of total protein). Glutaredoxins uniquely
      reduce mixed disulfides with glutathione via a monothiol mechanism where only an
      N-terminal low pKa Cys residue is required, by using their glutathione binding
      site. Glutaredoxins also catalyze formation of mixed disulfides
      (glutathionylation), which is an important redox regulatory mechanism,
      particularly in mammalian cells under oxidative stress conditions, to sense
      cellular redox potential.

PMID- 14713337
TI  - Increased plasma levels of thioredoxin in patients with coronary spastic angina.
AB  - To determine whether plasma levels of thioredoxin are associated with coronary
      spasm, we measured the plasma levels of thioredoxin in 170 patients who had <25%
      organic stenosis in coronary arteriography. According to the results of cardiac
      catheterization, we divided the patients into two groups: a coronary spastic
      angina group (n=84) and a chest pain syndrome group (n=86). The plasma levels of
      thioredoxin were significantly higher in the coronary spastic angina group than
      in the chest pain syndrome group (40.7 +/- 4.1 versus 18.2 +/- 1.1 ng/ml,
      p<0.0001). Furthermore, the increased plasma levels of thioredoxin were
      associated with high disease activity indicated by the frequency of angina
      attacks (p=0.0004). In multiple logistic regression analysis, the higher levels
      of thioredoxin [relative risk 14.8, 95% confidence interval (5.13-42.9),
      p<0.0001] and current smoking [relative risk 3.39, 95% confidence interval (1.31
      8.75), p=0.012] were significant and independent variables associated with
      coronary spasm. We demonstrated that the plasma levels of thioredoxin were
      increased in the coronary spastic angina group, and increased levels of
      thioredoxin were associated with high disease activity. The plasma levels of
      thioredoxin and current smoking were risk factors for coronary spastic angina,
      and they were independent from other traditional risk factors.

PMID- 14713338
TI  - Intravenous administration of thioredoxin decreases brain damage following
      transient focal cerebral ischemia in mice.
AB  - Thioredoxin (TRX) is induced by a variety of oxidative stimuli and shows
      cytoprotective roles against oxidative stress. To clarify the possibility of
      clinical application, we examined the effects of intravenously administered TRX
      in a model of transient focal cerebral ischemia in this study. Mature male
      C57BL/6j mice received either continuous intravenous infusion of recombinant
      human TRX (rhTRX) over a range of 1-10 mg/kg, bovine serum albumin, or vehicle
      alone for 2 h after 90-min transient middle cerebral artery occlusion (MCAO).
      Twenty-four hours after the transient MCAO, the animals were evaluated
      neurologically and the infarct volumes were assessed. Infarct volume,
      neurological deficit, and protein carbonyl contents, a marker of protein
      oxidation, in the brain were significantly ameliorated in rhTRX-treated mice at
      the dose of 3 and 10 mg/kg versus these parameters in control animals. Moreover,
      activation of p38 mitogen-activated protein kinase, whose pathway is involved in
      ischemic neuronal death, was suppressed in the rhTRX-treated mice. Further, rhTRX
      was detected in the ischemic hemisphere by western blot analysis, suggesting that
      rhTRX was able to permeate the blood-brain barrier in the ischemic hemisphere.
      These data indicate that exogenous TRX exerts distinct cytoprotective effects on
      cerebral ischemia/reperfusion injury in mice by means of its redox-regulating
      activity.

PMID- 14713339
TI  - Enhanced oxidative stress and impaired thioredoxin expression in spontaneously
      hypertensive rats.
AB  - As oxidative stress plays a crucial role in the development and pathogenesis of
      hypertension, we analyzed the redox (reduction/oxidation) status in tissues from
      Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone
      SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative
      stress-induced DNA damage, and protein carbonylation, a marker for oxidation
      status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP
      compared with WKY. The expression of redox regulating protein, thioredoxin (TRX),
      estimated by immunohistochemistry and western blot, and expression of TRX gene
      estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR
      and SHRSP compared with WKY. Induction of TRX was impaired after angiotension II
      treatment in peripheral blood mononuclear cells isolated from SHR and SHRSP
      compared with those isolated from WKY. Although previous reports have shown that
      TRX is induced by a variety of oxidative stress in tissues, the present study
      shows the impaired induction of TRX in tissues from genetically hypertensive rats
      despite the relative increment of oxidative stress. Redox imbalance in essential
      organs may play a crucial role in the development and pathogenesis of
      hypertension.

PMID- 14713340
TI  - Ebselen is a dehydroascorbate reductase mimic, facilitating the recycling of
      ascorbate via mammalian thioredoxin systems.
AB  - Ebselen is a selanazal drug recently revealed as a highly efficient peroxiredoxin
      mimic catalyzing the hydroperoxide reduction by the mammalian thioredoxin system
      [thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH]. The mammalian Trx
      system is a dehydroascorbic acid reductase recycling ascorbic acid essential for
      cell functions. Here we report that ebselen strongly facilitated the recycling of
      ascorbic acid by the TrxR both with and without Trx present. Reduction of
      dehydroascorbic acid by TrxR has a pH optimum of 6.4, and only approximately 55%
      of this activity at a physiological pH of 7.4. Ebselen at 6 microM enhances this
      reaction three-fold and with the same pH optimum of 6.4. The mechanism of the
      ebselen effect is suggested to involve reduction of dehydroascorbic acid by the
      ebselen selenol, a highly efficient two-electron reductant. Thus, ebselen acts as
      an antioxidant to lower the peroxide tone inside cells and to facilitate the
      recycling of dehydroascorbic acid to ascorbic acid, so as to increase the radical
      scavenging capacity of ascorbic acid directly or indirectly via vitamin E. The
      high ascorbic acid recycling efficiency of ebselen at pH 6.4 may play a major
      role in oxidatively stressed cells, where cytosol acidosis may trigger various
      responses, including apoptosis.

PMID- 14713341
TI  - Redox control of premature birth and newborn biology.

PMID- 14713342
TI  - Increased apoptosis and expression of p21 and p53 in premature infant baboon
      model of bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a major complication of premature infants who
      receive prolonged ventilatory support. The pathophysiology of BPD involves
      oxidant injury, baro/volutrauma, and disordered lung repair. Exposure of
      premature lung that is poorly adapted for air breathing (>3% oxygen in fetal
      lung) to a higher concentration of oxygen can cause significant oxidant injury.
      Cell growth and differentiation of the developing lung require selective and
      ordered cell division. As hyperoxia can increase the expression of cell-cycle
      checkpoints that can cause growth arrest of lung cells, in this report we
      examined the expression of checkpoint proteins p53 and p21 in a premature infant
      the baboon model of BPD. Additionally, we also determined whether enhanced
      apoptosis occurs in baboon BPD model. We have shown that p53 and p21 expression
      are increased in 125-day as well as 140-day premature baboons with BPD. We also
      demonstrate increased apoptosis in lung tissue of premature baboons with BPD.
      These results demonstrate that cell growth inhibition is a likely factor in the
      evolution of BPD. Additionally, lung cells may undergo increased apoptosis that
      can impair the repair process in the postventilatory recovery period.

PMID- 14713343
TI  - Altered expression of cyclins and cdks in premature infant baboon model of
      bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants,
      which results in substantial morbidity. The pathophysiology of BPD includes
      oxidant injury, baro/volutrauma, and disordered lung repair. As lung development,
      differentiation, and repair require cell division, we hypothesized dysregulation
      of the cell cycle in oxygen exposure of premature infants that may contribute to
      the evolution of BPD. In this investigation, we studied the expression of cyclins
      and cyclin-dependent kinases (cdks) that regulate transition from G1 and G2
      phases of the cell cycle. We report here that expression of cyclin D1, cyclin E,
      and cyclin A is modulated in premature baboons in respiratory distress. In
      addition, the expression of cdk1 or cdk4 was also modulated in these premature
      animals. The phosphorylation of retinoblastoma protein was progressively
      decreased in 125-day animals and in 140-day animals exposed to 6 or 14 days of
      PRN oxygen. These results indicate that due to altered cyclin and cdk expression,
      the repair of injured epithelium may proceed in a disordered manner that is
      characteristic of BPD. Thus, altered cell cycle regulation may be an important
      factor in the evolution of BPD.

PMID- 14713344
TI  - Hyperoxia-induced DNA damage causes decreased DNA methylation in human lung
      epithelial-like A549 cells.
AB  - The effect of hyperoxia on levels of DNA damage and global DNA methylation was
      examined in lung epithelial-like A549 cells. DNA damage was assessed by the
      single-cell gel electrophoresis (comet assay) and DNA methylation status by the
      cytosine extension assays. Cells exposed to ionizing radiation (0, 1, 2, 4, or 8
      Gy) showed increasing rates of percentage of DNA in the tail and tail length with
      increasing radiation dose. When cells were exposed to room air (normoxia) for 1
      day and 95% O2 (hyperoxia) for 1, 2, 3, 4, and 5 days, data indicated that
      hyperoxia caused time-dependent increases in levels of (a) single strand breaks,
      (b) double strand breaks, and (c) 8-oxoguanine. Decreased DNA methylation also
      was observed at day 5 of hyperoxic exposure, suggesting that hyperoxia-induced
      DNA damage can influence patterns of DNA methylation in a lung-derived cell line.

PMID- 14713345
TI  - Potential role for antiangiogenic proteins in the evolution of bronchopulmonary
      dysplasia.
AB  - Impaired neovascularization is associated with the pathologic presentation of
      bronchopulmonary dysplasia (BPD). To determine if neovascularization and factors
      that negatively influence blood vessel formation play a role in the evolution of
      BPD, we examined the temporospatial distribution of a protein known to inhibit
      fetal lung neovascularization with associated dysplastic lung formation,
      endothelial-monocyte activating polypeptide (EMAP) II. Immunohistochemical
      analysis of EMAP II in lung tissues of human infants with BPD indicated an
      elevation in EMAP II abundance as compared with control. Utilizing a baboon
      model, western analysis indicated that EMAP II was increased twofold in those
      baboons with pathologic signs of BPD as compared with gestational controls.
      Consistent with our findings in human tissues, immunohistochemistry and in situ
      hybridization demonstrate that EMAP II is highly expressed in the perivascular
      stroma and dysplastic lung periphery in neonatal baboons with BPD as compared
      with controls. Lastly, there is a premature acceleration in EMAP II's
      perivascular distribution in term newborn baboon as compared with gestational
      control. The marked increase in EMAP II's temporal expression, its distribution
      in the perivascular and dysplastic alveolar regions of the lungs, and the
      interruption in vasculogenesis in BPD suggest that neovascularization and factors
      that negatively influence blood vessel formation may play a role in BPD
      evolution.

PMID- 14713346
TI  - Role of redox in fetal development and neonatal diseases.
AB  - In the cell, reducing and oxidizing molecules modulate the redox state. In
      embryonic and fetal growth, increased oxidative stress may be detrimental, but an
      oxidized state can also be beneficial. This is because redox may also affect key
      transcription factors that can alter gene expression during development. In
      addition, redox may impact on placentation and amniotic membrane integrity during
      pregnancy. Lastly, diseases of prematurity, such as necrotizing enterocolitis,
      retinopathy of prematurity, and chronic lung disease, may be modulated by redox
      in the premature. Because antioxidant therapies have not necessarily modified the
      outcome of these diseases, some debate exists as to this. Nonetheless, sufficient
      evidence suggests a role for redox throughout embryonic, fetal, and postnatal
      development. This evidence will be explored here.

PMID- 14713347
TI  - Pulmonary antioxidant defenses in the preterm newborn with respiratory distress
      and bronchopulmonary dysplasia in evolution: implications for antioxidant
      therapy.
AB  - Preterm neonates with respiratory distress are exposed not only to the relative
      hyperoxia ex utero, but also to life-saving mechanical ventilation with high
      inspired oxygen (O2) concentrations, which is considered a major risk factor for
      the development of bronchopulmonary dysplasia, also referred to as chronic lung
      disease of infancy. O2 toxicity is mediated through reactive oxygen species
      (ROS). ROS are constantly generated as byproducts of normal cellular metabolism,
      but their production is increased in various pathological states, and also upon
      exposure to exogenous oxidants, such as hyperoxia. Antioxidants, either enzymatic
      or nonenzymatic, protect the lung against the deleterious effects of ROS.
      Expression of various pulmonary antioxidants is developmentally regulated in many
      species so that the expression is increased toward term gestation, as if in
      anticipation of birth into an O2-rich extrauterine environment. Therefore, the
      lungs of prematurely born infants may be ill-adapted for protection against ROS.
      While premature birth interrupts normal lung development, the clinical condition
      necessitating the administration of high inhaled O2 concentrations may lead to
      permanent impairment of alveolar development. An understanding of the processes
      involved in lung growth, especially in alveolarization and vascularization, as
      well as in repair of injured lung tissue, may facilitate development of
      strategies to enhance these processes.

PMID- 14713348
TI  - Free radicals and diseases in premature infants.
AB  - Free radicals have been implicated in the pathogenesis of a wide spectrum of
      human diseases. Premature infants are probably developmentally unprepared for
      extrauterine life in an oxygen-rich environment and exhibit a unique sensitivity
      to oxidant injury. Diseases associated with premature infants, including
      bronchopulmonary dysplasia, periventricular leukomalacia, intraventricular
      hemorrhage, retinopathy of prematurity, and necrotizing enterocolitis, have been
      linked to free radical-mediated cell and tissue injury. With the advent of
      therapies designed to combat the injurious effects of free radicals, the role of
      these highly reactive chemical molecules in the pathogenesis of neonatal diseases
      needs to be fully determined.

PMID- 14713349
TI  - Thioredoxin system in premature and newborn biology.
AB  - Thioredoxin is an important redox protein that is ubiquitously distributed.
      Thioredoxin exists in dynamic equilibrium between the oxidized and reduced forms,
      making it an ideal redox-regulatory protein. Thioredoxin, together with
      thioredoxin reductase and peroxiredoxins, forms a complete redox system that is
      similar to the glutathione system, but with distinct and divergent functions.
      This review provides a brief general summary of the thioredoxin system with
      particular emphasis on its role in premature birth and newborn physiology and
      disease states. Although extensive studies have examined the role of the
      thioredoxin system in antioxidant defense, cell proliferation, and signal
      transduction, further studies are needed to understand its role in embryogenesis
      and development. Such studies will facilitate our understanding of how
      thioredoxin may modulate newborn diseases via redox regulation.

PMID- 14713350
TI  - Regulation of surfactant protein gene expression by hyperoxia in the lung.
AB  - Pulmonary surfactant, a complex of lipids and proteins, maintains alveolar
      integrity and participates in the control of host defense and inflammation in the
      lung. Surfactant proteins A, B, C, and D are important components of surfactant
      that play diverse roles in the surface tension reducing as well as host defense
      and inflammation control functions of surfactant. Hyperoxia or exposure of
      cells/tissues to elevated levels of oxygen occurs when high levels of oxygen are
      used to treat a variety of pulmonary disorders that include respiratory distress
      syndrome of premature infants, emphysema, sarcoidosis, end-stage lung diseases,
      and others. The lung serves as a primary target organ in hyperoxia, and hyperoxic
      lung injury is characterized by pulmonary edema, inflammation, and respiratory
      failure. Hyperoxic lung injury is associated with significant changes in the
      expression of surfactant proteins that likely serves as an adaptive response to
      elevated oxygen levels. In most animal species studied, hyperoxia increases the
      tissue expression of surfactant protein mRNAs. A limited number of studies have
      indicated that the increased tissue expression of surfactant protein mRNAs is
      associated with increased levels of surfactant proteins in the bronchoalveolar
      lavage.

PMID- 14713351
TI  - Combined superoxide dismutase/catalase mimetics alter fetal pulmonary arterial
      smooth muscle cell growth.
AB  - Reactive oxygen species (ROS) are known to play an important role in the
      proliferation and viability of vascular smooth muscle cells. We have shown
      previously that treatment of fetal pulmonary arterial smooth muscle cells
      (FPASMC) with concentrations of 25 microM and higher of EUK-134, a superoxide
      dismutase/catalase mimetic, decreased cell viability via the induction of
      apoptosis. Here we demonstrate a dose-dependent decrease in serum-induced FPASMC
      growth at lower doses of EUK-134. This was due to the attenuation of FPASMC
      proliferation rather than the induction of apoptosis. Moreover, we found that the
      inhibition of FPASMC proliferation was observed using EUK-134 at concentrations
      as low as 5 microM. This inhibition of proliferation correlated with a 31%
      decrease in superoxide levels, as estimated using the oxidation of
      dihydroethidium. Flow cytometry revealed an increase in FPASMC in G2 after 24 h
      of exposure to 10 microM EUK-134. This was associated with a twofold increase in
      levels of the cell-cycle regulatory protein p21. This, together with our previous
      data, suggests that ROS levels determine the rate of FPASMC proliferation and,
      when below a threshold level, trigger apoptosis. Titration of ROS with
      antioxidants may help to prevent, or reverse, the vascular remodeling manifest in
      many cardiovascular disease states.

PMID- 14713355
TI  - The potential of chitosan in ocular drug delivery.
AB  - This paper presents an overview of the potential of chitosan-based systems for
      improving the retention and biodistribution of drugs applied topically onto the
      eye. Besides its low toxicity and good ocular tolerance, chitosan exhibits
      favourable biological behaviour, such as bioadhesion- and permeability-enhancing
      properties, and also interesting physico-chemical characteristics, which make it
      a unique material for the design of ocular drug delivery vehicles. The review
      summarizes the techniques for the production of chitosan gels, chitosan-coated
      colloidal systems and chitosan nanoparticles, and describes their mechanism of
      action upon contact with the ocular mucosa. The results reported until now have
      provided evidence of the potential of chitosan gels for enhancing and prolonging
      the retention of drugs on the eye surface. On the other hand, chitosan-based
      colloidal systems were found to work as transmucosal drug carriers, either
      facilitating the transport of drugs to the inner eye (chitosan-coated colloidal
      systems containing indometacin) or their accumulation into the
      corneal/conjunctival epithelia (chitosan nanoparticles containing ciclosporin).
      Finally, the tolerance, toxicity and biodegradation of the carriers under
      evaluation were reviewed.

PMID- 14713356
TI  - Ampicillin micronization by supercritical assisted atomization.
AB  - The micronization technique called supercritical assisted atomization (SAA) was
      used to produce ampicillin microparticles with controlled particle size and
      particle size distribution suitable for aerosol drug delivery. The process is
      based on the solubilization of supercritical CO2 in a liquid solution. The
      ternary mixture is then sprayed through a nozzle and, as a consequence of
      enhanced atomization, solid microparticles are formed. Water and organic solvents
      were tested with ampicillin to determine the influence of the solvent on the
      process mechanism. SAA process parameters were studied by testing different
      supercritical/liquid solvent flow ratios, ampicillin concentrations in the liquid
      solution and nozzle diameters. The effect of these parameters on morphology,
      particle size and particle size distribution of microparticles was analysed.
      Ampicillin particles suitable for aerosol delivery in the size range 1-5 microm
      were obtained using buffered water. Moreover, by varying the solute
      concentration, ampicillin particles in a narrower range (1-3 microm) than that
      usually suggested for aerosol deliverable drugs were obtained. This is an example
      of particle size tailoring by SAA.

PMID- 14713357
TI  - Effects of oxygen plasma treatment on the surface wettability and dissolution of
      furosemide compacts.
AB  - The plasma irradiation of furosemide (frusemide) was investigated as a possible
      technique for increasing the dissolution rate of this drug. Oxygen plasma was
      used to generate oxygen-containing functional groups on the surface of the
      compact to increase the wettability of the surface and the dissolution rate of
      the drug. Compacts of furosemide (300 mg) were produced using a stainless steel
      die and punch assembly, which was placed into a KBr press. The time of the plasma
      treatment was varied to assess the effect if any upon the dissolution rate and
      the wettability of the drug. Dissolution experiments of the plasma-treated and
      untreated compacts were carried out using the paddle apparatus method.
      Dissolution was carried out at 37 degrees C using 1 L of 0.1 M HCl and phosphate
      buffer (pH 6). The wettability was assessed by contact angle measurements using
      the sessile drop technique. Untreated and plasma-treated samples were analysed by
      scanning electron microscopy at x 5000 magnification. Plasma treatment was found
      to lower the equilibrium contact angle from approximately 50 to 35 degrees but
      the dissolution rate was not significantly affected. This was attributed to
      fusion of the surface by the plasma treatment.

PMID- 14713358
TI  - Evaluation of the bitterness of antibiotics using a taste sensor.
AB  - The bitterness of nine commercial antibiotics (clarithromycin, erythromycin,
      cefdinil, doxycycline, vancomycin, tetracycline, minocycline, oxytetracycline and
      bacampicillin) was evaluated in human gustatory sensation tests with nine
      volunteers. The bitterness of 0.1-0.3 mM solutions (or suspensions in the case of
      clarithromycin) of the antibiotics was then measured using an artificial
      multichannel taste sensor. In the sensor measurements, three variables were used
      to predict estimated bitterness in single and multiple regression analysis and
      principal component analysis: sensor output as relative value (R), the change of
      membrane potential caused by adsorption (C) and C/R. Particularly good
      correlation was obtained between obtained bitterness scores and predicted scores
      using C from channel 2 of the sensor (r2=0.870, P<0.005) and C/R values for
      channels 2 and 3 (r2=0.947, P<0.005). The taste sensor was also successful in
      assessing the bitterness intensity of clarithromycin powder suspensions of
      various concentrations. Clarithromycin has a low aqueous solubility but is the
      most bitter of the nine antibiotics. Sensory data from channel 3 of the sensor
      predicted the bitterness of clarithromycin powder suspensions and their filtered
      solutions well. Finally, the bitterness intensity of a commercial clarithromycin
      dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co. Ltd, Tokyo,
      Japan) was evaluated in gustatory sensation tests and using the taste sensor. In
      Clarith dry syrup the drug is coated with aminoalkyl methacrylate polymer using a
      spray congealing method. The taste sensor results confirmed that the polymer was
      successful in almost completely masking the bitter taste of the dry syrup
      product.

PMID- 14713359
TI  - Magnetic resonance imaging study of the transport phenomena of solvent into the
      gel layer of hypromellose matrices containing tetracycline hydrochloride.
AB  - Magnetic resonance imaging was used to study the diffusion of a water solution of
      hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices.
      Spatially resolved information was obtained about the self-diffusion coefficient
      and spin-spin relaxation time of solvent protons in the gel layer of hypromellose
      matrices loaded with different amounts of tetracycline hydrochloride. The data
      showed the influence of the drug concentration on the diffusion and spin-spin
      relaxation. Higher drug concentrations in the hypromellose matrix led to greater
      swelling of the matrix and faster diffusion of the water molecules inside the gel
      layer of the polymer. The observed differences between the radial and axial
      diffusion were interpreted in terms of the stresses imposed in the axial
      direction during the compression of the samples. The spin-spin and diffusion
      profiles indicated that the diffusion of a water solution of hydrochloric acid
      into hypromellose, pure and loaded with different amounts of tetracycline
      hydrochloride, was characterized as a Case II mechanism.

PMID- 14713360
TI  - Kinetic studies of the degradation of an aminopenicillin antibiotic (amoxicillin
      trihydrate) in aqueous solution using heat conduction microcalorimetry.
AB  - Recent developments in isothermal microcalorimetry allow the direct determination
      of kinetic and thermodynamic parameters for slow reactions from studies conducted
      at appropriate temperatures and under designated environmental control. The
      degradation kinetics of amoxicillin trihydrate has been investigated as a
      function of pH (1-10) and temperature (303.15-318.15 K) at 0.5 M ionic strength
      using heat conduction microcalorimetry. Equations were developed incorporating
      calorimetric accessible data, rate constants and change in enthalpy, which showed
      that the degradation of amoxicillin trihydrate in aqueous solution followed
      pseudo-first-order kinetics under our experimental conditions. The enthalpy of
      degradation reaction was found to be exothermic in nature. The values of the rate
      constant k for individual steps were determined from the values of the overall
      rate constants at different pH. Energy of activation of overall reaction as a
      function of pH and for individual rate constants was determined. The log k-pH
      profiles indicated specific-acid and specific-base catalysis and there were
      inflection points near pH 3 and pH 7 corresponding to the pKa1 and pKa2 values.
      Quantitatively, there was good correlation between calorimetric determined half
      life (t1/2) and the literature value in the acidic region determined by other
      methods at 310.15 K. The presence of a beta-lactam ring and of an alpha-amino
      group in the C-6 side chain played a critical role in the degradation of
      amoxicillin trihydrate and the zwitterionic form of the drug was found to be more
      stable.

PMID- 14713361
TI  - Transdermal iontophoresis of insulin. Part 1: A study on the issues associated
      with the use of platinum electrodes on rat skin.
AB  - We have studied the issues associated with the use of platinum electrodes for
      transdermal iontophoretic delivery of peptides, using insulin as a model peptide.
      Insulin permeation was studied using full-thickness rat skin by varying the donor
      solution pH as a function of electrode polarity. The stability of insulin under
      the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel
      electrophoresis and HPLC. Large pH shifts were observed during anodal
      iontophoresis (AI), when the donor solution pH was above the isoelectric point of
      insulin and in cathodal iontophoresis (CI), when the donor solution pH was below
      the isoelectric point of insulin. The direction and magnitude of electroosmotic
      flow was influenced by pH of the donor solution and the electrode polarity. On
      the other hand, the buffer used to maintain the pH governed the contribution of
      electrorepulsion to the overall transport of insulin. Electrochemical degradation
      of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of
      insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively
      less and electrochemically more stable during iontophoresis as compared with
      other pH. In summary, the pH shift caused by platinum electrodes had a
      significant influence on the permeation and stability of insulin.

PMID- 14713362
TI  - Effects of the rate and composition of fluid replacement on the pharmacokinetics
      and pharmacodynamics of intravenous torasemide.
AB  - The effects of differences in the rate and composition of intravenous fluid
      replacement for urine loss on the pharmacokinetics and pharmacodynamics of
      torasemide were evaluated in rabbits. Each rabbit received 2-h constant
      intravenous infusion of 1 mg kg(-1) torasemide with 0% replacement (treatment 1,
      n=6), 50% replacement (treatment 2, n=9), 100% replacement with lactated Ringer's
      solution (treatment 3, n=8), and 100% replacement with 5% dextrose in water
      (treatment 4, n=6). Total body (4.53, 5.72, 10.0 and 4.45 mL min(-1) kg(-1) for
      treatments 1-4, respectively) and renal clearance (1.44, 1.87, 6.78 and 1.72 mL
      min(-1) kg(-1)) of torasemide, and total amount of unchanged torasemide excreted
      in 8-h urine (A(e 0-8 h): 694, 780, 1310 and 1040 microg) in treatment 3 were
      considerably faster and greater compared with treatments 1, 2 and 4. Although the
      difference in A(e 0-8 h) between treatments 1 and 3 was only 88.8%, the diuretic
      and/or natriuretic effects of torasemide were markedly different among the four
      treatments. For example, the mean 8-h urine output was 101, 185, 808 and 589 mL
      for treatments 1-4, respectively, and the corresponding values for sodium
      excretion were 10.1, 20.6, 89.2 and 29.9 mmol, and for chloride excretion were
      14.5, 27.9, 94.0 and 37.2 mmol. Although full fluid replacement was used in both
      treatments 3 and 4, the 8-h diuretic, natriuretic and chloruretic effects in
      treatment 3 were significantly greater compared with treatment 4, indicating the
      importance of the composition of fluid replacement. Both treatments 1 and 4
      received no sodium replacement, however, the 8-h diuretic, natriuretic and
      chloruretic effects were significantly greater in treatment 4 compared with
      treatment 1, indicating the importance of rate of fluid replacement for the
      diuretic effects. Therefore, the 8-h diuretic, natriuretic and chloruretic
      effects were significantly greater in treatment 3 compared with treatments 1, 2
      and 4, indicating the importance of full fluid and electrolyte replacement. Some
      implications for the bioequivalence evaluation of dosage forms of torasemide are
      discussed.

PMID- 14713363
TI  - Potential utility of various protease inhibitors for improving the intestinal
      absorption of insulin in rats.
AB  - The aim of the investigation was to study the effects of protease inhibitors on
      the absorption of insulin in-situ from closed small and large intestinal loops in
      rats and to investigate the mechanism of various protease inhibitors in different
      intestinal loops. The intestinal absorption of insulin was evaluated by its
      hypoglycaemic effect and serum insulin level in the presence or absence of
      luminal contents. No marked hypoglycaemic effect was observed after
      administration of insulin alone in either region in the presence or absence of
      luminal contents. A significant hypoglycaemic effect of insulin was obtained in
      the large intestinal loop in the presence or absence of luminal contents when
      insulin was co-administered with bacitracin (20, 30 mM), sodium glycocholate (20,
      40 mM), bestatin (29 mM), leupeptin (21 mM) and cystatin (0.8 mM). In contrast,
      there was no hypoglycaemic effect in the small intestinal loop in the presence of
      luminal contents following small intestinal co-administration of insulin with
      these protease inhibitors. The effectiveness of protease inhibitors was
      susceptible to their categories, concentrations and activity of proteolytic
      enzymes in different regions. The degree of improving insulin absorption in
      intestine was in the order of leupeptin>sodium
      glycocholate>bacitracin>bestatin>cystatin. At the same time, the percutaneous
      enhancement effect was observed in the presence of either sodium glycocholate or
      bacitracin. These results suggest that protease inhibitors could increase the
      insulin efficacy more effectively in the large intestine than in the small
      intestine.

PMID- 14713364
TI  - Persistent reversal of P-glycoprotein-mediated daunorubicin resistance by
      tetrandrine in multidrug-resistant human T lymphoblastoid leukemia MOLT-4 cells.
AB  - Multidrug resistance (MDR) represents a major problem in cancer chemotherapy. P
      glycoprotein (P-gp), the drug efflux pump that mediates this resistance, can be
      inhibited by compounds with a variety of pharmacological functions, thus
      circumventing the MDR phenotype. The present study was performed to evaluate a
      unique MDR-reversal feature of a bisbenzylisoquinoline alkaloid tetrandrine (TET)
      in a P-gp expressing MOLT-4 MDR line (MOLT-4/DNR) established in our laboratory.
      Cell viability was determined by an MTT assay. P-gp function was characterized by
      determining the Rh123 accumulation/efflux capacity. P-gp overexpression in
      resistant MOLT-4/DNR cells was confirmed by flow cytometry analysis after
      staining with phycoerythrin-conjugated anti-P-gp monoclonal antibody 17F9.
      Compared to ciclosporin A (CsA), TET exhibited stronger activity to reverse drug
      resistance to daunorubicin (DNR), vinblastine (VLB) and doxorubicin (DOX) in MOLT
      4/DNR cells. TET showed no cytotoxic effects on parental MOLT-4 cells lacking P
      gp expression or on the resistant MOLT-4/DNR cells. TET modulated DNR
      cytotoxicity even after it was washed with the medium for 24 h, while CsA almost
      completely lost its reversal capability 24 h after washing. TET and CsA similarly
      increased the accumulation of Rh123 in resistant MOLT-4/DNR cells. However, TET
      inhibited Rh123 efflux from resistant cells even after washing with the medium,
      while CsA rapidly lost its ability to inhibit Rh123 efflux after washing. The
      current study suggests that TET enhances the cytotoxicity of anticancer drugs in
      the P-gp expressing MDR cell line by modulating P-gp in a different manner to the
      well-known P-gp inhibitor CsA.

PMID- 14713365
TI  - Non-genomic effects of tamoxifen on the activation of membrane-bound guanylate
      cyclase GC-A.
AB  - Oestrogen is known to exert both genomic and non-genomic effects on target
      tissues. Unlike the genomic effects, the identity of receptors mediating the non
      genomic effects of oestrogen remains controversial. 17beta-estradiol has been
      shown to activate membrane-bound guanylate cyclase GC-A in PC12 cells in a non
      genomic manner. To examine whether 17beta-estradiol exerts a similar effect in
      other cell types, we measured the effect of 17beta-estradiol and tamoxifen, an
      anti-oestrogen, on guanylate cyclase activity in porcine kidney proximal tubular
      LLC-PK1 cells. 17beta-estradiol increased cGMP levels in LLC-PK1 cells.
      Interestingly, addition of tamoxifen also increased cGMP levels in a
      concentration-dependent manner in LLC-PK1 cells. The effects of both 17beta
      estradiol and tamoxifen on guanylate cyclase activity were not additive,
      suggesting that oestrogen and tamoxifen activate the same enzyme. Similar
      phenomena were also observed in LLC-PK1 cell membrane preparation. LLC-PK1 cells
      do not express membrane-bound guanylate cyclase GC-B and express low levels of
      membrane-bound guanylate cyclase GC-C. Tamoxifen inhibited the activation of GC-A
      by atrial natriuretic factor (ANF). However, it did not affect membrane-bound
      guanylate cyclase GC-C stimulated by guanylin or Escherichia coli heat-stable
      toxin STa. These results indicate that 17beta-estradiol and tamoxifen activate GC
      A in LLC-PK1 cells. Thus, tamoxifen functions as an agonist rather than an
      antagonist for the membrane oestrogen receptor coupled to the activation of GC-A.

PMID- 14713366
TI  - Significance of measured elevation of skin temperature induced by calcitonin gene
      related peptide in anaesthetized rats.
AB  - To assess whether peripheral changes related to skin temperature rise were
      induced by ovarian hormone deficiency, we investigated the effects of anaesthesia
      on calcitonin gene-related peptide (CGRP)- or luteinizing hormone-releasing
      hormone (LH-RH)-induced elevation of skin temperature in female rats. CGRP was
      used as an inducer of peripherally-mediated elevation of skin temperature,
      whereas LH-RH was used as an inducer of centrally-mediated elevation of skin
      temperature. Intravenous (i.v.) but not intracerebroventricular injection of CGRP
      (10 microg kg(-1)) or intracerebroventricular but not intravenous injection of LH
      RH (10 microg/rat) elevated the skin temperature of unanaesthetized rats
      restrained in a Ballman's cage. The elevation with LH-RH was completely inhibited
      by urethane anaesthesia, whereas the elevation with CGRP was not. These results
      suggested that changes in skin temperature measured under anaesthesia reflected a
      peripherally rather than a centrally mediated mechanism. The CGRP (1.0-30 microg
      kg(-1), i.v.)-induced elevation of skin temperature was potentiated in
      ovariectomized rats and inhibited by pretreatment with a CGRP receptor antagonist
      CGRP(8-37) (1000 microg kg(-1), i.v.), suggesting that the potentiation may
      participate in peripheral factors such as a postsynaptic hypersensitivity to CGRP
      following ovarian hormone deficiency. Thus, measurement of skin temperature in
      the anaesthetized rat was a useful procedure to seek the peripheral mechanism of
      potentiation of skin temperature induced by CGRP, thought to be closely related
      to menopausal hot flashes.

PMID- 14713367
TI  - The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on
      two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man.
AB  - The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components
      (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root,
      Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with
      chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the
      activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man.
      Twenty-six healthy subjects were studied to evaluate their baseline activity of
      CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample
      after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio
      of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the
      subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and
      underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2
      decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001).
      The mean activity of XO also significantly decreased by 25% on day 1 and 20% on
      day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended
      to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko
      to reduces CYP1A2 and XO activity in man.

PMID- 14713368
TI  - Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride
      induced hepatic fibrosis in rats.
AB  - Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive
      trichloromethyl radical that triggers a chain of lipid peroxidation. These
      changes lead to cell injury, and chronic liver injury leads to excessive
      deposition of collagen in liver, resulting in liver fibrosis. The aim of this
      study was to evaluate the effects of long-term Salvia miltiorrhiza administration
      in CCl4-induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg(
      1) twice a day) was given for 9 weeks, beginning at the same time as the
      injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic
      glutathione level and an increased glutathione-S-transferase content. The hepatic
      thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused
      a prominent collagen deposition in liver histology that was further supported by
      the increased hepatic mRNA expression of transforming growth factor-beta1, tissue
      inhibitor of metalloproteinase-1 and procollagen I. Salvia miltiorrhiza
      administration led to a dose-dependent increase in hepatic glutathione levels and
      a decrease in peroxidation products. Additionally, it reduced the mRNA expression
      of markers for hepatic fibrogenesis. In conclusion, long-term administration of
      Salvia miltiorrhiza in rats ameliorated the CCl4-induced hepatic injury that
      probably related to a reduced oxidant stress and degree of hepatic fibrosis.

PMID- 14713369
TI  - Repetitive administration of Shaoyao-Gancao-tang to rats restores the
      bioavailability of glycyrrhizin reduced by antibiotic treatment.
AB  - Shaoyao-Gancao-tang (SGT), a traditional Chinese formulation, is often used
      together with antibiotics such as amoxicillin and metronidazole (AMPC-MET) for
      the treatment of peptic ulcers in Japan. However, the bioavailability of
      glycyrrhizin (GL) in SGT is severely reduced by a single administration of AMPC
      MET, and the reducing effect continues for 12 days. GL is one of the major
      pharmacologically important glycosides in SGT and is transformed into the active
      metabolite 18beta-glycyrrhetic acid (GA) by intestinal bacteria in the gut,
      followed by absorption of the latter into the blood. In order to reduce the
      negative effect of AMPC-MET on the bioavailability of GL, the optimum scheduling
      of the medications was examined. We found that the reduction in the plasma GA
      concentration and the GL-metabolizing activity in faeces caused by a single dose
      of AMPC-MET could be sharply attenuated by the repetitive administration of SGT
      for 4 days. The GA concentration and the GL-metabolizing activity were strongly
      enhanced by further continuous administration of SGT. These findings suggest that
      repetitive administration of SGT starting 1 or 2 days after the administration of
      AMPC-MET speeds the recovery of the bioavailability of GL in SGT. Similar
      strategies for administering medications may also be useful for combination
      therapy of antibiotics with other traditional Chinese formulations containing
      bioactive glycosides.

PMID- 14713370
TI  - Inhibitory effect of salmosin, a Korean snake venom-derived disintegrin, on the
      integrin alphav-mediated proliferation of SK-Mel-2 human melanoma cells.
AB  - We have investigated the inhibitory effect of salmosin on integrin-mediated human
      tumour cell proliferation. SK-Mel-2 human melanoma cell adhesion to denatured
      collagen or vitronectin was found to be significantly and statistically inhibited
      by salmosin in a dose-dependent manner (P<0.05). Moreover, the binding of SK-Mel
      2 cells to salmosin-coated plates was specifically disrupted by anti-integrin
      alphav monoclonal antibody at 8 microg mL(-1), but not by anti-integrin
      monoclonal antibody. These findings indicated that salmosin inhibited the
      adhesion of SK-Mel-2 cells to denatured collagen by specifically blocking
      integrin alphav. The proliferation of SK-Mel-2 cells on a denatured collagen
      coated plate was statistically and significantly inhibited by salmosin induced
      apoptosis in a dose-dependent manner (P<0.05). Anti-integrin alphav monoclonal
      antibody, anti-integrin alphavbeta3 monoclonal antibody, and synthetic RGD
      peptide also suppressed SK-Mel-2 cell proliferation. Several lines of
      experimental evidence strongly suggested that the inhibition of SK-Mel-2 cell
      proliferation by salmosin was due to the induction of apoptosis via the blocking
      of integrin alphav-mediated cell survival.

PMID- 14713371
TI  - Metabolites of orally administered Magnolia officinalis extract in rats and man
      and its antidepressant-like effects in mice.
AB  - As a part of our search for the active metabolite from the bark of Magnolia
      officinalis (Magnoliaceae), the aqueous extract was orally administered to rats,
      and metabolites in the urine were analysed by a high-performance liquid
      chromatograph equipped with a photodiode array detector. When the extract was
      given to rats, five metabolites (sinapic acid-4-O-sulfate (1), sinapic acid-4-O
      beta-glucuronide (2), sinapic acid (3), 3-[2',6-dihydroxy-5'-(2-propenyl)[1,1'
      biphenyl]-3-yl]-(E)-2-propenoic acid (4), and an unchanged form, magnolol (5))
      were detected in the urine. It was revealed that metabolites 1-3 and 4 were
      respectively derived from syringin and magnolol contained in the extract. In a
      human urine sample, metabolites 3-5 and dihydroxydihydromagnolol (6) were
      detected. These structures were identified by a combination of spectral methods
      and/or by comparison with authentic compounds obtained by synthesis. Among these
      free form metabolites (3-6), acute treatments with magnolol and
      dihydroxydihydromagnolol (50-100 mg kg(-1), i.p.) attenuated the forced swim
      induced experimental depression in mice. The results indicated that magnolol and
      dihydroxydihydromagnolol were the antidepressant constituents of Magnolia
      officinalis.

PMID- 14713372
TI  - The effects of metacognitive training versus worked-out examples on students'
      mathematical reasoning.
AB  - BACKGROUND: The present study is rooted in a cognitive-metacognitive approach.
      The study examines two ways to structure group interaction: one is based on
      worked-out examples (WE) and the other on metacognitive training (MT). Both
      methods were implemented in cooperative settings, and both guided students to
      focus on the problem's essential parts and on appropriate problem-solving
      strategies. AIMS: The aim of the present study is twofold: (a) to investigate the
      effects of metacognitive training versus worked-out examples on students'
      mathematical reasoning and mathematical communication; and (b) to compare the
      long-term effects of the two methods on students' mathematical achievement.
      SAMPLE: The study was conducted in two academic years. Participants for the first
      year of the study were 122 eighth-grade Israeli students who studied algebra in
      five heterogeneous classrooms with no tracking. In addition, problem-solving
      behaviours of eight groups (N = 32) were videotaped and analysed. A year later,
      when these participants were ninth graders, they were re-examined using the same
      test as the one administered in eighth grade. METHOD: Three measures were used to
      assess students' mathematical achievement: a pretest, an immediate post-test, and
      a delayed post-test. ANOVA was carried out on the post-test scores with respect
      to the following criteria: verbal explanations, algebraic representations and
      algebraic solution. In addition, chi-square and Mann-Whitney procedures were used
      to analyse cooperative, cognitive, and metacognitive behaviours. RESULTS: Within
      cooperative settings, students who were exposed to metacognitive training
      outperformed students who were exposed to worked-out examples on both the
      immediate and delayed post-tests. In particular, the differences between the two
      conditions were observed on students' ability to explain their mathematical
      reasoning during the discourse and in writing. Lower achievers gained more under
      the MT than under WE condition. CONCLUSIONS: The findings indicate that the kind
      of task and the way group interaction is structured are two important variables
      in implementing cooperative learning, each of which is likely to have different
      effects on mathematical communication and achievement outcomes.

PMID- 14713373
TI  - Evaluating change in attitude towards mathematics using the 'then-now' procedure
      in a cooperative learning programme.
AB  - BACKGROUND: Tertiary students' attitudes to mathematics are frequently negative
      and resistant to change, reflecting low self-efficacy. Some educators believe
      that greater use should be made of small group, collaborative teaching. However,
      the results of such interventions should be subject to assessments of bias caused
      by a shift in the frame of reference used by students in reporting their
      attitudes. AIMS: This study was designed to assess whether traditional pretest
      post-test procedures would indicate positive changes in mathematics attitude
      during a programme of cooperative learning, and whether an examination of any
      attitudinal change using the 'then-now' procedure would indicate bias in the
      results due to a shift in the internal standards for expressing attitude. SAMPLE:
      Participants were 141 undergraduate students enrolled in a 12-week statistics and
      research design component of a course in educational psychology. METHOD: Using
      multivariate procedures, pretest, post-test, and then-test measures of
      mathematics self-concept and anxiety were examined in conjunction with a
      cooperative learning approach to teaching. RESULTS: Significant positive changes
      between pretest and post-test were found for both mathematics self-concept and
      mathematics anxiety. There were no significant differences between the actual
      pretest and retrospective pretest measures of attitude. The results were not
      moderated by prior level of mathematics study. CONCLUSION: Conclusions about the
      apparent effectiveness of a cooperative learning programme were strengthened by
      the use of the retrospective pretest procedure.

PMID- 14713374
TI  - The efficiency of multimedia learning into old age.
AB  - BACKGROUND: On the basis of a multimodal model of working memory, cognitive load
      theory predicts that a multimedia-based instructional format leads to a better
      acquisition of complex subject matter than a purely visual instructional format.
      AIMS: This study investigated the extent to which age and instructional format
      had an impact on training efficiency among both young and old adults. It was
      hypothesised that studying worked examples that are presented as a narrated
      animation (multimedia condition) is a more efficient means of complex skill
      training than studying visually presented worked examples (unimodal condition)
      and solving conventional problems. Furthermore, it was hypothesised that
      multimedia-based worked examples are especially helpful for elderly learners, who
      have to deal with a general decline of working-memory resources, because they
      address both mode-specific working-memory stores. SAMPLE: The sample consisted of
      60 young (mean age = 15.98 years) and 60 old adults (mean age = 64.48 years).
      METHODS: Participants of both age groups were trained in either a conventional, a
      unimodal, or a multimedia condition. Subsequently, they had to solve a series of
      test problems. Dependent variables were perceived cognitive load during the
      training, performance on the test, and efficiency in terms of the ratio between
      these two variables. RESULTS: Results showed that for both age groups multimedia
      based worked examples were more efficient than the other training formats in that
      less cognitive load led to at least an equal performance level. CONCLUSION:
      Although no difference in the beneficial effect of multimedia learning was found
      between the age groups, multimedia-based instructions seem promising for the
      elderly.

PMID- 14713375
TI  - Approaches to learning, need for cognition, and strategic flexibility among
      university students.
AB  - BACKGROUND: Considerable research has described students' deep and surface
      approaches to learning. Other research has described individuals' self-regulated
      learning and need for cognition. There is a need for research examining the
      relationships among these constructs. AIMS: This study explored relationships
      among approaches to learning (deep, surface), need for cognition, and three types
      of control of learning (adaptive, inflexible, irresolute). Theory suggested
      similarities among the deep approach, need for cognition, and adaptive control
      (aspects of self-regulated learning); and among surface, inflexible, and
      irresolute control (aspects of an ineffective approach to learning). One-factor
      and two-factor models were proposed. SAMPLE: Participants were 226 Canadian
      military college students. METHOD: Participants completed the following
      questionnaires: the Study Process Questionnaire (Biggs, 1978), the Need for
      Cognition Scale (Cacioppo & Petty, 1982), and the Strategic Flexibility
      Questionnaire (Cantwell & Moore, 1996). RESULTS: Confirmatory factor analysis
      supported the identification of the six scale factors. Second order confirmatory
      factor analysis indicated three factors representing constructs underlying these
      factors. CONCLUSIONS: Neither the one- nor two-factor models accounted adequately
      for the data. Self-regulated learning was defined by measures of the deep
      approach to learning, need for cognition, and adaptive control of learning. The
      second factor divided into one factor consisting of irresolute control, the
      surface approach, and negative need for cognition; and another consisting of
      inflexible and negative adaptive control. Substantial relationships among scales
      support the need for further theory development.

PMID- 14713376
TI  - The trichotomous model and investment in learning to prepare for a sport test: a
      mediational analysis.
AB  - BACKGROUND: Contemporary views on motivation suggest that the approach-avoidance
      achievement goals conceptualization--namely the trichotomous model--can shed
      light on the important issue of student motivation. AIMS: To test the predictive
      value of the trichotomous model on the investment in learning a sport task for
      test preparation, and to validate a model which included a set of psychological
      processes (i.e., state anxiety and competence valuation) which mediate the
      relationship between the three goals (i.e., performance-approach, performance
      avoidance, and mastery goals) and test preparation. The study was designed to
      investigate the direct and mediational effects of three experimental goal
      conditions on the time in which pupils prepared for a sport test. SAMPLE: French
      male school pupils (N = 75). Pupils were aged 13-15 years and attended schools in
      southern France. METHOD: Pupils prepared themselves for a sport task with a 5
      minute period of training, and performed in one of three experimental conditions
      to which they were randomly assigned: a performance goal with a positive outcome
      focus (performance-approach), a performance goal with a negative outcome focus
      (performance-avoidance), or a mastery goal. RESULTS: Pupils in the performance
      avoidance group reported higher state anxiety and lower competence valuation than
      those in the performance-approach and mastery groups, and this psychological
      state was associated with less time taken to prepare for the test. CONCLUSION:
      School pupils placed in an examination preparation context that elicits a
      performance goal with a negative outcome focus (performance-avoidance) show
      motivational deficits which manifest themselves in less time spent practising.
      The trichotomous model appears to be valid for the study of motivational
      processes in school physical education.

PMID- 14713377
TI  - Intervention in children with Developmental Coordination Disorder: the role of
      parents and teachers.
AB  - BACKGROUND: Children with Developmental Coordination Disorder (DCD) are a
      heterogeneous group who have a marked impairment in the performance of functional
      skills. Provision for these children is usually made via a paediatrician through
      occupational or physiotherapy though, with a prevalence rate of 5%, regular
      provision is not possible due to limited professional resources. AIMS: The study
      aimed to determine the extent to which parents and teachers, with guidance, can
      assist in the management of children with DCD; whether children with DCD are
      helped in this way and how this may contribute to our understanding of the
      condition. SAMPLE: Thirty-one children with DCD aged 7 to 9 years participated in
      the study. METHODS: Following assessment, individual profiles were developed and
      each week teachers and parents were given guidelines for working with the
      children and each child had three to four sessions a week lasting approximately
      for 20 minutes. In Phase 1, one group of children worked with teachers and the
      other group worked with parents. In Phase 2, the two groups of children swapped
      over. The children were assessed regularly throughout the project using the
      Movement ABC, together with diaries and comments from teachers and parents.
      RESULTS: At the end of the 40-week study, 27 children showed significant
      improvement in their motor skills. CONCLUSIONS: Both teachers and parents were
      able to provide effective intervention for the majority of the children. It is
      possible that the children who did not improve have difficulties that are of a
      more complex type which require more specialist therapy to meet their need.

PMID- 14713378
TI  - Academic attainments of children with Down's syndrome: a longitudinal study.
AB  - BACKGROUND: Studies of the academic progress of schoolchildren with Down's
      syndrome have given only limited indication of attainments at different ages.
      Such normative data, it is argued, could guide professionals and parents in
      respect to reasonable expectations and typical achievement. AIMS: The aim of the
      paper is to provide a descriptive account of levels and range of academic
      attainments reached by a representative sample of children with Down's syndrome
      over time. SAMPLE: Data relate to 106 children from three studies with the same
      cohort of families. Mean age was 9.1 years at the first study (1986), 13.7 at the
      second (1991), and 21.1 at the third (2000). Mean IQ was 40.29. METHODS: The
      Academic Attainments Index (AAI) covers reading, writing and numeracy, and was
      designed for teacher completion. In order to compare attainments to wider norms,
      scores were compiled by age group, and related to age-specific National
      Curriculum attainment levels, which are similar to US school grades. RESULTS: AAI
      scores were obtained for 102 individuals in 1986, 101 in 1991 and 79 in 2000.
      Comparisons across age groups indicate that higher scores were achieved by each
      successive age group up to age 20, and that this pattern held for both more and
      less able children. Once adjusted for differences in IQ scores between age
      groups, however, there was some evidence of a levelling off towards the end of
      the school career. By school-leaving age, the more able children reached at least
      some National Curriculum Key Stage 2 targets in reading and writing, and some Key
      Stage 3 targets in number work. CONCLUSION: Results provide a detailed picture of
      attainments across ability and age

PMID- 14713379
TI  - Children's early reading vocabulary: description and word frequency lists.
AB  - BACKGROUND: When constructing stimuli for experimental investigations of
      cognitive processes in early reading development, researchers have to rely on
      adult or American children's word frequency counts, as no such counts exist for
      English children. AIM: The present paper introduces a database of children's
      early reading vocabulary, for use by researchers and teachers. SAMPLE: Texts from
      685 books from reading schemes and story books read by 5-7 year-old children were
      used in the construction of the database. METHOD: All words from the 685 books
      were typed or scanned into an Oracle database. RESULTS: The resulting up-to-date
      word frequency list of early print exposure in the UK is available in two forms
      from a website address given in this paper. This allows access to one list of the
      words ordered alphabetically and one list of the words ordered by frequency. We
      also briefly address some fundamental issues underlying early reading vocabulary
      (e.g., that it is heavily skewed towards low frequencies). Other characteristics
      of the vocabulary are then discussed. CONCLUSIONS: We hope the word frequency
      lists will be of use to researchers seeking to control word frequency, and to
      teachers interested in the vocabulary to which young children are exposed in
      their reading material.

PMID- 14713380
TI  - The significance of serum troponin T in patients with kidney disease: a review of
      the literature.
AB  - The last 10 years have witnessed radical changes in the definition and diagnosis
      of the acute coronary syndrome (ACS), including myocardial infarction, as a
      result of the introduction of sensitive and specific markers of myocardial
      damage, the cardiac troponins. One barrier to the universal acceptance of these
      markers has been the observation that troponin T (cTnT) concentration is commonly
      increased in the presence of renal failure. Initially it was believed that this
      constituted an important false positive limitation of the test. This was
      confounded by problems with the initial cTnT assay and by the observation that
      troponin I (cTnI) was generally not increased in these patients. However, it has
      recently been demonstrated that the prognostic significance of a raised cTnT
      concentration in patients with a suspected ACS is unaffected by renal impairment.
      Further, powerful outcome studies are now being reported demonstrating that
      raised concentrations of serum cTnT are predictive of mortality in haemodialysis
      patients. This review summarizes our current understanding of the prevalence and
      significance of raised serum cTnT concentrations in patients with kidney disease
      and highlights areas where our understanding is incomplete. Evidence suggests
      that raised troponin concentrations in uraemic patients do indeed reflect
      myocardial injury. In the future, patients demonstrating this abnormality may be
      the target for more aggressive cardiac intervention, the advantages of which have
      been demonstrated in the non-uraemic population.

PMID- 14713381
TI  - The emergence of type 2 diabetes in childhood.
AB  - Type 1 diabetes (with predominant insulin deficiency) was until recently assumed
      to be the diagnosis of almost all children presenting with glucose intolerance.
      This requires insulin treatment via subcutaneous injections, and most patients
      develop microvascular and macrovascular complications in adulthood. Advances in
      genetics in the 1990s identified a group of genetic disorders of pancreatic beta
      cell function (maturity-onset diabetes of the young) for which the outlook is
      better than type 1, genetic testing is available, and oral medication is the
      preferred treatment. In 2000, the first cases of type 2 diabetes (predominant
      insulin resistance) were reported in UK children, reflecting a trend seen in
      North America over the last 20 years. Affected children are usually overweight or
      obese, often female, pubertal, predominantly of ethnic minority (South Asian)
      origin and have a family history of type 2 diabetes. The diagnosis is aided by
      demonstration of insulin resistance, and may include measurement of fasting
      insulin and C-peptide, markers of the metabolic syndrome (fasting lipids, sex
      hormone binding globulin) and absence of autoantibodies against beta-cell
      components (e.g. glutamic acid decarboxylase). Management is aimed towards weight
      stabilization in the growing child, education on healthy lifestyles and the
      treatment of hyperglycaemia with both insulin and insulin-sensitizing agents. The
      underlying cause of type 2 diabetes in children is likely to be related to the
      epidemic of childhood obesity. There is emerging evidence of an appalling outlook
      for these young people in terms of miscarriages and microvascular and
      cardiovascular complications, which are likely to present an enormous economic
      and health services burden over the next 20 years.

PMID- 14713382
TI  - Measurement of catecholamines and their metabolites.
AB  - Analysis of the low levels of catecholamines and metabolites in tissue and
      biological fluids has necessitated the use of highly sensitive analytical
      techniques. Earlier procedures utilizing radioenzymatic and immunological assays,
      gas chromatography or fluorimetry have generally been superseded by highly
      sensitive and selective chromatographic methods utilizing electrochemical or
      fluorimetric detection. The development of high-performance liquid chromatography
      (HPLC) methods for the measurement of plasma metadrenalines and the combination
      of HPLC with tandem mass spectrometry provides additional procedures with minimum
      interference from drugs and drug metabolites. This review summarizes the
      methodology currently available for the measurement of catecholamines and
      metabolites in plasma and urine, the influence of sample collection protocols and
      the clinical application of the methods for the biochemical detection of
      catecholamine-secreting tumours.

PMID- 14713383
TI  - Formate buffer as preservative for urinary free catecholamine measurement.
AB  - BACKGROUND: Strong mineral acid is the most commonly used preservative for
      measuring urinary free catecholamines. Leakage of corrosive acid is a safety
      hazard. The use of formate buffer as a safer alternative was studied. METHODS:
      Twenty-two urine specimens from post-operative patients were collected and
      preserved in 0.5 M hydrochloric acid or 0.75 M formate buffer. The specimens were
      stored at 4 degrees C or -70 degrees C, respectively. The free catecholamine
      content was measured at regular intervals by high-performance liquid
      chromatography for 6 months. RESULTS: The preservation capability of formate
      buffer was equivalent to that of hydrochloric acid. Deep-freeze storage offered
      additional protection independent of the preservative used. CONCLUSION: The
      results of this study demonstrate that formate buffer, compared to the most
      popularly used strong mineral acid solution, is an equally effective preservation
      for urinary free catecholamines. The less acidic nature of formate should invite
      fewer unpleasant incidents and safety hazards.

PMID- 14713384
TI  - A new antiglycolytic agent.
AB  - BACKGROUND: Glycolysis is not completely or predictably inhibited by the glucose
      preservative currently in use, with glucose values falling by as much as 0.5
      mmol/L during a 2-4-h period after sample collection. Immediate centrifugation of
      all samples is also impractical and therefore misdiagnosis of disease can occur,
      especially if more emphasis is being placed on fasting glucose for the diagnosis
      of diabetes. METHODS: Glycolysis at room temperature was evaluated over time
      using glyceraldehyde alone as well as in conjunction with standard antiglycolytic
      agents. RESULTS: Glyceraldehyde alone does not inhibit glycolysis completely. The
      combination of 11 mmol/L glyceraldehyde, 119 mmol/L sodium fluoride and 21.7
      mmol/L potassium oxalate gave the best antiglycolytic results. The glucose values
      measured in samples stored at room temperature for 48 h was no different from
      those measured in samples centrifuged immediately after venepuncture and this is
      clinically superior to conventionally used sodium fluoride and potassium oxalate.
      CONCLUSION: Plasma glucose concentrations obtained from blood collected into
      tubes containing glyceraldehyde, sodium fluoride and potassium oxalate will more
      closely reflect those of the patient at venepuncture.

PMID- 14713385
TI  - The perennial problem with potassium.
AB  - BACKGROUND: The problem of spurious hyperkalaemia in blood samples delivered to
      hospitals from local general practitioners' (GP) surgeries remains a source of
      diagnostic confusion and potential danger to patients. We have carried out
      retrospective and prospective audits of serum potassium measurements to assess
      the influences of blood sample delivery time and temperature during transit from
      GP surgeries to a centralized laboratory on the risk of spurious serum potassium
      measurements. METHOD: The retrospective audit included serum potassium
      measurements made by the pathology laboratory at Addenbrooke's Hospital on 51 843
      patients attending either the hospital itself or one of 62 local GP surgeries
      during the months August 2001 to February 2002 (i.e. summer through to winter).
      The probability of spurious potassium measurements on GP patients relative to
      blood sample delivery time and temperature was modelled by least-squares multiple
      linear regression. The prospective audit included serum potassium measurements
      made on 40 patients presenting early in the day at the Sutton GP surgery near
      Ely, Cambridgeshire, during the months February to May 2002. RESULTS: Low blood
      sample delivery temperature had a greater impact on the probability of spurious
      potassium measurements than long delivery time. Low delivery temperature also had
      a greater impact on the probability of spurious hyperkalaemia than it had on the
      probability of spurious normokalaemia. At temperatures below 20.3 degrees C, the
      probabilities of both spurious hyper- and normokalaemia for samples delivered
      from the most distant and closest GP surgeries to Addenbrooke's increased
      significantly. CONCLUSIONS: Maintaining blood sample delivery temperatures a few
      degrees above 20 degrees C will minimize the risk of spurious serum potassium
      measurements on samples from GP patients.

PMID- 14713386
TI  - Improving the quality of information on pathology request forms.
AB  - BACKGROUND: We have investigated the causes of incomplete pathology request forms
      received at our clinical chemistry laboratory. Based on a request form audit we
      found that the data most frequently missing from a pathology request form was the
      doctor's name, unique identification provider number, or signature. METHODS: We
      examined the effect of issuing the requesting doctors with self-inking stamps
      personalized with their name and a unique provider number. RESULTS: The
      intervention led to an immediate and sustained improvement in compliance, with
      the proportion of incomplete forms falling from 43% to 2%. In contrast,
      distribution of a memorandum alone made no significant change to the number of
      pathology request forms with incomplete data arriving at the laboratory.
      CONCLUSION: This study describes a simple and low-cost solution to one of the
      causes of incomplete pathology request forms. It also demonstrates the
      effectiveness of systems improvement in health care.

PMID- 14713387
TI  - Polymorphism of Trp64Arg in beta3-adrenergic receptor gene among Bolivian people
      in rural areas at high and low altitudes.
AB  - BACKGROUND: To investigate whether population differences in food and/or
      lifestyle could affect the distribution frequencies of polymorphism in the gene
      for beta3-adrenergic receptor (beta3-AR), the frequency of Trp64Arg polymorphism
      was studied among Bolivian people living in rural areas of high (about 4000 m
      above sea level) and low (about 300 m above sea level) altitudes. METHODS:
      Genomic DNA samples of Bolivian subjects (n=508) were amplified by polymerase
      chain reaction (PCR) for part of the beta3-AR gene. The amplified PCR products
      were digested with restriction enzyme NciI and analysed by agarose gel
      electrophoresis. RESULTS: We found no significant difference in the frequency of
      Arg allele in the beta3-AR gene between 331 native low-altitude Bolivian subjects
      (18.1%) and 177 native high-altitude Bolivian subjects (17.5%). Body mass index
      was not associated with Trp64Arg polymorphism among native Bolivian adults. The
      frequency of this allele in the complete Bolivian population (18%) was lower than
      that reported in Pima Indians (32%), is comparable to the Japanese (19%) and is
      higher than several ethnic groups, including Finns (12%) and French (4%).
      CONCLUSIONS: Our data indicate that the altitude-related lifestyle of a
      population has had little influence on the frequency of Trp64Arg polymorphism and
      obesity in Bolivian natives.

PMID- 14713388
TI  - Determination of the total protein and triglyceride content of human breast milk
      on the Synchron CX7 Delta analyser.
AB  - BACKGROUND: Premature babies have improved clinical outcomes when fed breast milk
      with a relatively high protein content. Since there was no convenient way of
      measuring the macronutrition of breast milk we used our routine laboratory
      pyrogallol red dye binding method for cerebrospinal fluid microprotein (MTP) and
      our routine method for serum triglyceride to determine the total protein and
      triglyceride content of human breast milk. METHODS: The total protein contents of
      whole and defatted breast milk samples, randomly collected from 115 nursing
      mothers, analysed using a pyrogallol red dye binding assay on a Synchron CX7
      Delta analyser were compared with the total protein contents determined by dry
      combustion analysis. Triglyceride concentrations, determined on the Synchron CX7
      Delta analyser were compared with their respective creamatocrits. RESULTS:
      Passing and Bablok regression analysis (95% confidence interval) gave the
      following regression equations: y = 5.98(5.48 to 6.56)x-1.32(-2.02 to -0.73)
      where y is whole milk MTP (g/L) and x is dry combustion analysis (g/100 g); y =
      7.09 (6.54 to 7.78)x-2.44 (-3.46 to -1.67) where y is volume-corrected defatted
      milk MTP (g/L) and x is dry combustion analysis (g/100 g); y = 7.52 (6.86 to
      8.24)x+0.90(-2.42 to 3.37) where y is whole milk triglyceride (mmol/L) and x is
      creamatocrit (%). CONCLUSION: The Synchron CX7 Delta total protein and
      triglyceride assays provide practical, rapid and reliable methods for the
      determination of the macronutrition in human milk.

PMID- 14713389
TI  - An audit of biological monitoring of industrial lead workers by a UK laboratory
      over a 2-year period.
AB  - BACKGROUND: Medical surveillance of workers in the lead industry is under the
      statutory control of the Control of Lead at Work Act (CLAW). Over the years the
      CLAW regulations have been updated with a reduction in the suspension
      concentration for blood lead and the introduction of an action limit. As a result
      of these changes, an audit of blood lead measurement together with an evaluation
      of haemoglobin and zinc protoporphyrin (ZPP) measurements, also requested as part
      of surveillance, is required. METHODS: Results of measurements for blood lead,
      ZPP and haemoglobin in lead-exposed workers in 58 industries within the UK were
      collected over a 2-year period. RESULTS: For male workers, 8.8% of blood lead
      results [range 1-88 microg/dL (0.05-4.25 micromol/L), median 29 microg/dL (1.4
      micromol/L), n = 3010] were above the action limit and 5.6% above the suspension
      limit set by CLAW. For female workers, 1.9% of blood lead results [range 1-74
      micro g/dL (0.05-3.58 micromol/L), median 7 microg/dL (0.34 micromol/L), n = 161]
      were above the action limit. No significant correlation was found between blood
      lead and haemoglobin in the male workers (rs =-0.04, P = 0.024) and only a slight
      negative correlation for the female workers (rs =-0.25, P = 0.0016). ZPP showed
      an exponential relationship with blood lead in the male workers with a wide
      scatter of results. CONCLUSION: Haemoglobin and ZPP offer little towards the
      assessment of lead exposure in industrial workers. Blood lead in accordance with
      the CLAW regulations still offers the most appropriate means of industrial
      monitoring.

PMID- 14713390
TI  - A new method of measuring the antioxidant activity of polyphenols using cumene
      hydroperoxide.
AB  - BACKGROUND: It is well known that polyphenols lower the risk of chronic diseases
      such as heart disease and cancer. We describe a new method using cumene
      hydroperoxide (CHP) to determine the antioxidant activity of polyphenols. CHP is
      considered to be a model reactive lipid peroxidation product. METHODS: The method
      was based on two reactions: the reduction of a known concentration of CHP by
      polyphenols and the reaction of the remaining CHP with a methylene blue
      derivative (10-N-methylcarbamoyl-3,7 dimethylamino-10H-phenothiazine) in the
      presence of haemoglobin. Methylene blue was formed as a result of the two
      reactions and then measured by absorbance at 675 nm. We named this assay the
      'cumene hydroperoxide/haemoglobin.methylene blue (CHP/Hb.MB) method'. We examined
      13 polyphenols and nine compounds known to be antioxidants. RESULTS: Among the 13
      polyphenols, milicetin, with the largest number of hydroxyl groups, had the
      highest antioxidant activity, followed by cyanidin, pelargonidin and quercetin.
      It is suggested that the increase in the number of hydroxyl groups induced a
      higher antioxidant activity. Within-run coefficients of variation were 3.6% and
      3.5% at the mean antioxidant activity of 50 micromol/L and 151 micromol/L,
      respectively. CONCLUSION: We conclude that this CHP/Hb.MB assay is capable of
      measuring the antioxidant activity of polyphenols.

PMID- 14713391
TI  - Limitations of faecal elastase-1 and chymotrypsin as tests of exocrine pancreatic
      disease in adults.
AB  - BACKGROUND: The faecal enzymes elastase and chymotrypsin are a relatively
      inexpensive non-invasive means of investigating causes of malabsorption. However,
      such tests may be affected by enzyme degradation or faecal dilution. METHODS:
      Faecal elastase-1 and chymotrypsin were measured in 225 patients in whom
      pancreatic disease was suspected, and the association between faecal free water
      and pH with these faecal enzymes was examined in subjects with normal pancreatic
      function. RESULTS: The sensitivity of faecal elastase-1 and chymotrypsin for
      identifying exocrine pancreatic disease was 75% and 60%, respectively.
      Corresponding specificities for excluding disease were 95% and 97%. The positive
      predictive value for faecal elastase-1 increased from 58% to 92% when watery
      diarrhoea was excluded. Faecal elastase-1 (inversely) and chymotrypsin (directly)
      were significantly associated with percentage faecal free water content in
      subjects without pancreatic disease. Faecal elastase-1 was not related to faecal
      pH, whereas chymotrypsin was inversely related to pH. CONCLUSION: Faecal elastase
      1 is a more sensitive test for exocrine pancreatic disease in adults but is
      affected by dilution in patients with watery diarrhoea. The value of faecal
      chymotrypsin is limited by intestinal degradation.

PMID- 14713392
TI  - Pseudonormokalaemia caused by recentrifugation of blood samples after storage in
      gel-separator tubes.

PMID- 14713397
TI  - Genetics of osteoarthritis.
AB  - Osteoarthritis (OA) is a major cause of morbidity, physical limitation, and
      health care use, including total joint arthroplasty. That OA has a genetic
      component has been known for some time, but only recently has formal study of
      this occurred. Twin studies, segregation analyses, linkage analyses, and
      candidate gene association studies have generated important information about
      inheritance patterns and the location in the genome of potentially causative
      mutations. Results across studies are not always concordant, however; this is
      likely the result of variations in study populations, disease definitions,
      evaluation of control subjects, and statistical analysis. Although the genetics
      of OA is complex and not completely understood, there is cause for optimism as
      rapidly improving technologies make the quest for the genes responsible for OA
      increasingly within reach. Family history of OA and joint replacement for OA
      should be assessed in the context of other potentially modifiable risk factors to
      attempt to alter patient outcome.

PMID- 14713398
TI  - Does osteoarthritis of the lumbar spine cause chronic low back pain?
AB  - The lumbar spine is a common location for osteoarthritis. The axial skeleton
      demonstrates the same classic alterations of cartilage loss, joint instability,
      and osteophytosis characteristic of symptomatic disease in the appendages.
      Despite these similarities, questions remain regarding the lumbar spine facet
      joints as a source of chronic back pain. The facet joints undergo a progression
      of degeneration that may result in pain. The facet joints have sensory input from
      two spinal levels that makes localization of pain difficult. Radiographic studies
      describe intervertebral disc abnormalities in asymptomatic individuals that are
      associated with, but not synonymous for, osteoarthritis. Patients who do not have
      osteoarthritis of the facet joints on magnetic resonance scan do not have back
      pain. Single photon emission computed tomography scans of the axial skeleton are
      able to identify painful facet joints with increased activity that may be helped
      by local anesthetic injections. Low back pain is responsive to therapies that are
      effective for osteoarthritis in other locations. Osteoarthritis of the lumbar
      spine does cause low back pain.

PMID- 14713400
TI  - Gene therapies for osteoarthritis.
AB  - Osteoarthritis (OA) is a major health problem in urgent need of better treatment.
      Gene therapy offers to meet this need. Of the different strategies for using gene
      therapy in OA, local gene transfer to synovium is in the most advanced stage of
      development. Local gene transfer brings several advantages, including a focused,
      local therapy that promises greater efficacy with reduced side-effects,
      potentially at far lower cost. Moreover, its clinical feasibility has already
      been confirmed in two Phase I studies of gene therapy for rheumatoid arthritis.
      Although there are numerous candidate genes of potential use in treating OA
      genetically, considerable evidence identifies interleukin-1 (IL-1) as a key
      target. The existence of a natural antagonist, the IL-1 receptor antagonist (IL
      1Ra), provides a means with which to inhibit its biologic actions. Clinical
      studies are suggested in which IL-1Ra complementary DNA is transferred to knee
      joints shortly before they are surgically replaced with prostheses. This will
      permit the ready assessment of the safety and efficiency of gene transfer and
      expression in the human OA knee, as well as permitting preliminary functional
      data to be obtained, as a prelude to phase II efficacy studies. At this point,
      the major barriers to progress are financial rather than intellectual or
      technical.

PMID- 14713399
TI  - Outcome measures in osteoarthritis: randomized controlled trials.
AB  - Accepted outcome measures in randomized controlled trials (RCTs) in
      osteoarthritis (OA) include patient-reported assessments of physical function and
      health-related quality of life (HRQOL). Available data can inform treatment
      decisions when statistically significant changes are viewed in terms of
      clinically important improvements. Patient-reported outcomes validated in OA
      include global assessments of pain, disease activity, and disease-specific and
      generic measures of physical function and HRQOL. Definitions of minimum
      clinically important differences (MCID) have been derived from RCTs with physical
      therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2
      selective agents. Definitions of MCID should serve only as guidelines based on
      mean changes in a treatment group, and do not necessarily reflect clinically
      meaningful improvements for an individual patient. They help to interpret data
      across treatments and patient populations. Definitions of MCID may differ for the
      type of intervention assessed; additional methodologic issues must be addressed
      when evaluating nonpharmacologic treatments. Based on RCTs in OA evaluating
      physical therapy, cyclooxygenase-2 agents, and NSAIDs, the Western Ontario and
      McMaster Osteoarthritis Index is valid, reliable, sensitive to change, and
      correlates closely with the generic Medical Outcomes Survey Short-Form 36 measure
      of HRQOL. When evaluating RCT data, understanding derivation and MCID values of
      outcome measures facilitates informed therapeutic decisions regarding therapeutic
      interventions.

PMID- 14713401
TI  - The use of glucosamine therapy in osteoarthritis.
AB  - Glucosamine products have been used extensively for the management of pain in
      osteoarthritis. This paper reviews the most recent clinical and experimental
      studies regarding its efficacy and safety. Although clinical trials include
      methodologic flaws and publication bias, glucosamine is likely an effective
      therapy for the symptomatic management of osteoarthritis. In turn, definite proof
      for chondromodulating effect requires well-conducted clinical trials. In North
      America, glucosamine is an over-the-counter dietary supplement and preparations
      made by different manufacturers may vary. There is also a need to standardize
      this therapy and allow practitioners to give patients suitable advice. An ongoing
      long-term clinical trial in the US will possibly permit to investigate the
      clinical relevance of these results and give appropriate recommendations.

PMID- 14713402
TI  - The use of intermittent human parathyroid hormone as a treatment for
      osteoporosis.
AB  - Parathyroid hormone (PTH), given intermittently, is an anabolic agent. PTH has
      been demonstrated to increase bone mass and reduce vertebral and nonvertebral
      fractures, and has been approved for use in the US and Europe. PTH is a
      genetically engineered 34 amino acid protein with the designation teriparatide
      (recombinant DNA origin) or recombinant human PTH 1-34. A recombinant DNA
      preparation with all 84 amino acids of the native PTH molecule is in clinical
      trials. These PTH preparations are self-administered daily injections, and it is
      approved for women and men at high risk for fractures, including patients with
      prevalent fractures, low bone mass, and multiple risk factors. PTH is likely to
      be used most frequently in patients who fracture on therapy, but can be used in
      high-risk treatment-naive patients. Previous treatment with alendronate appears
      to impair the anabolic response of PTH preparations. Patients who have Paget's
      disease, prior radiation therapy to the skeleton, as well as children and young
      adults with open epiphyses, are at higher risk for osteosarcoma and should not be
      given PTH. Patients with hypercalcemia and hyperparathyroidism also should not
      receive the drug.

PMID- 14713403
TI  - An update on bisphosphonates.
AB  - Over the past 15 years, bisphosphonates have been demonstrated as effective
      therapy for the treatment of osteoporosis based on their ability to suppress bone
      turnover resulting in increased bone mineral content and increased bone strength.
      The mechanism of action at the cellular level has been identified, and the more
      potent nitrogen-containing bisphosphonates clearly have reduced the risk of
      vertebral and nonvertebral fractures in patients with osteoporosis. Future use of
      these therapies is evolving to less frequent administration, and the interaction
      with anabolic therapies is presently being defined. Data to date support long
      term safety with bisphosphonates in small numbers of patients treated for 5 to 10
      years, and continued vigilant follow-up of the post-marketing experience will be
      necessary to determine if sustained bone turnover suppression is associated with
      rare musculoskeletal adverse events. Further development of bisphosphonates as
      adjunctive therapy to reduce bone metastases is in progress, and trials
      evaluating bisphosphonates as a structure modifying agent in osteoarthritis are
      nearing completion.

PMID- 14713404
TI  - US and UK guidelines for glucocorticoid-induced osteoporosis: similarities and
      differences.
AB  - Osteoporosis is a common and serious complication of glucocorticoid therapy.
      Recent advances in the epidemiology, pathophysiology, and management of
      glucocorticoid-induced osteoporosis have stimulated the development of guidelines
      for the prevention and treatment of this condition. In this report, the updated
      recommendations of the American College of Rheumatology and guidelines recently
      produced by the Bone and Tooth Society, National Osteoporosis Society, and Royal
      College of Physicians in the UK are discussed with respect to their similarities
      and differences.

PMID- 14713405
TI  - Bone disease in pediatric rheumatologic disorders.
AB  - Children with rheumatic disorders have multiple risk factors for impaired bone
      health, including delayed growth and development, malnutrition, decreased weight
      bearing activity, inflammation, and glucocorticoid therapy. The impact of
      rheumatic disease during childhood may be immediate, resulting in fragility
      fractures, or delayed, because of suboptimal peak bone mass accrual. Recent years
      have seen increased interest in the effects of pediatric rheumatic disorders on
      bone mineralization, such as juvenile rheumatoid arthritis, systemic lupus
      erythematosus, and juvenile dermatomyositis. This review outlines the expected
      gains in bone size and mass during childhood and adolescence, and summarizes the
      advantages and disadvantages of available technologies for the assessment of
      skeletal growth and fragility in children. The varied threats to bone health in
      pediatric rheumatic disorders are reviewed, with emphasis on recent insights into
      the molecular mechanisms of inflammation-induced bone resorption. The literature
      assessing bone deficits and risk factors for impaired bone health in pediatric
      rheumatic disorders is reviewed, with consideration of the strengths and
      limitations of prior studies. Finally, future research directions are proposed.

PMID- 14713406
TI  - Is it ethical to use placebos in osteoporosis clinical trials?
AB  - Because there are now effective agents for treatment of osteoporosis, the
      question is being raised as to whether or not it is ethical to have placebo
      controlled trials of new agents. It is ethical for patients who are at low risk
      of serious or irreversible harm to participate in placebo-controlled trials as
      long as they provide informed consent. Morbidity, mortality, and future fracture
      risk correlate with the presence of previous fractures, the number of previous
      fractures, whether or not the fracture is recent, and whether or not the fracture
      is clinically recognized. Lower-risk subjects who may be allowed to participate
      in placebo-controlled trials include those with low bone density but without a
      previous vertebral fracture, those with a single vertebral deformity that was not
      clinically recognized, and those with a vertebral fracture more than 2 years
      before. Higher-risk subjects who do not tolerate proven drugs or who have not
      responded to proven drugs may also participate. Even though it may be ethical for
      selected subjects to participate in placebo-controlled trials of new therapies
      for osteoporosis, steps should be taken to minimize their exposure (eg,
      unbalanced randomization, integration of outcomes, and powering trials to actual
      events rather than a projected number over 3 years), and treating patients who
      fracture or who fail to respond.

PMID- 14713407
TI  - Mixture model for inferring susceptibility to mastitis in dairy cattle: a
      procedure for likelihood-based inference.
AB  - A Gaussian mixture model with a finite number of components and correlated random
      effects is described. The ultimate objective is to model somatic cell count
      information in dairy cattle and to develop criteria for genetic selection against
      mastitis, an important udder disease. Parameter estimation is by maximum
      likelihood or by an extension of restricted maximum likelihood. A Monte Carlo
      expectation-maximization algorithm is used for this purpose. The expectation step
      is carried out using Gibbs sampling, whereas the maximization step is
      deterministic. Ranking rules based on the conditional probability of membership
      in a putative group of uninfected animals, given the somatic cell information,
      are discussed. Several extensions of the model are suggested.

PMID- 14713408
TI  - The effect of using approximate gametic variance covariance matrices on marker
      assisted selection by BLUP.
AB  - Under additive inheritance, the Henderson mixed model equations (HMME) provide an
      efficient approach to obtaining genetic evaluations by marker assisted best
      linear unbiased prediction (MABLUP) given pedigree relationships, trait and
      marker data. For large pedigrees with many missing markers, however, it is not
      feasible to calculate the exact gametic variance covariance matrix required to
      construct HMME. The objective of this study was to investigate the consequences
      of using approximate gametic variance covariance matrices on response to
      selection by MABLUP. Two methods were used to generate approximate variance
      covariance matrices. The first method (Method A) completely discards the marker
      information for individuals with an unknown linkage phase between two flanking
      markers. The second method (Method B) makes use of the marker information at only
      the most polymorphic marker locus for individuals with an unknown linkage phase.
      Data sets were simulated with and without missing marker data for flanking
      markers with 2, 4, 6, 8 or 12 alleles. Several missing marker data patterns were
      considered. The genetic variability explained by marked quantitative trait loci
      (MQTL) was modeled with one or two MQTL of equal effect. Response to selection by
      MABLUP using Method A or Method B were compared with that obtained by MABLUP
      using the exact genetic variance covariance matrix, which was estimated using
      15,000 samples from the conditional distribution of genotypic values given the
      observed marker data. For the simulated conditions, the superiority of MABLUP
      over BLUP based only on pedigree relationships and trait data varied between 0.1%
      and 13.5% for Method A, between 1.7% and 23.8% for Method B, and between 7.6% and
      28.9% for the exact method. The relative performance of the methods under
      investigation was not affected by the number of MQTL in the model.

PMID- 14713409
TI  - Full conjugate analysis of normal multiple traits with missing records using a
      generalized inverted Wishart distribution.
AB  - A Markov chain Monte Carlo (MCMC) algorithm to sample an exchangeable covariance
      matrix, such as the one of the error terms (R0) in a multiple trait animal model
      with missing records under normal-inverted Wishart priors is presented. The
      algorithm (FCG) is based on a conjugate form of the inverted Wishart density that
      avoids sampling the missing error terms. Normal prior densities are assumed for
      the 'fixed' effects and breeding values, whereas the covariance matrices are
      assumed to follow inverted Wishart distributions. The inverted Wishart prior for
      the environmental covariance matrix is a product density of all patterns of
      missing data. The resulting MCMC scheme eliminates the correlation between the
      sampled missing residuals and the sampled R0, which in turn has the effect of
      decreasing the total amount of samples needed to reach convergence. The use of
      the FCG algorithm in a multiple trait data set with an extreme pattern of missing
      records produced a dramatic reduction in the size of the autocorrelations among
      samples for all lags from 1 to 50, and this increased the effective sample size
      from 2.5 to 7 times and reduced the number of samples needed to attain
      convergence, when compared with the 'data augmentation' algorithm.

PMID- 14713410
TI  - Genetic analysis of a divergent selection for resistance to Rous sarcomas in
      chickens.
AB  - Selection for disease resistance related traits is a tool of choice for
      evidencing and exploring genetic variability and studying underlying resistance
      mechanisms. In this framework, chickens originating from a base population,
      homozygote for the B19 major histocompatibility complex (MHC) were divergently
      selected for either progression or regression of tumors induced at 4 weeks of age
      by a SR-D strain of Rous sarcoma virus (RSV). The first generation of selection
      was based on a progeny test and subsequent selections were performed on full
      sibs. Data of 18 generations including a total of 2010 birds measured were
      analyzed for the tumor profile index (TPI), a synthetic criterion of resistance
      derived from recording the volume of the tumors and mortality. Response to
      selection and heritability of TPI were estimated using a restricted maximum
      likelihood method with an animal model. Significant progress was shown in both
      directions: the lines differing significantly for TPI and mortality becoming null
      in the "regressor" line. Heritability of TPI was estimated as 0.49 +/- 0.05 and
      0.53 +/- 0.06 within the progressor and regressor lines respectively, and 0.46 +/
      0.03 when estimated over lines. Preliminary results showed within the progressor
      line a possible association between one Rfp-Y type and the growth of tumors.

PMID- 14713411
TI  - QTL detection and allelic effects for growth and fat traits in outbred pig
      populations.
AB  - Quantitative trait loci (QTL) for growth and fatness traits have previously been
      identified on chromosomes 4 and 7 in several experimental pig populations. The
      segregation of these QTL in commercial pigs was studied in a sample of 2713
      animals from five different populations. Variance component analysis (VCA) using
      a marker-based identity by descent (IBD) matrix was applied. The IBD coefficient
      was estimated with simple deterministic (SMD) and Markov chain Monte Carlo (MCMC)
      methods. Data for two growth traits, average daily gain on test and whole life
      daily gain, and back fat thickness were analysed. With both methods, seven out of
      26 combinations of population, chromosome and trait, were significant.
      Additionally, QTL genotypic and allelic effects were estimated when the QTL
      effect was significant. The range of QTL genotypic effects in a population varied
      from 4.8% to 10.9% of the phenotypic mean for growth traits and 7.9% to 19.5% for
      back fat trait. Heritabilities of the QTL genotypic values ranged from 8.6% to
      18.2% for growth traits, and 14.5% to 19.2% for back fat. Very similar results
      were obtained with both SMD and MCMC. However, the MCMC method required a large
      number of iterations, and hence computation time, especially when the QTL test
      position was close to the marker.

PMID- 14713412
TI  - Estimating the frequency of Asian cytochrome B haplotypes in standard European
      and local Spanish pig breeds.
AB  - Mitochondrial DNA has been widely used to perform phylogenetic studies in
      different animal species. In pigs, genetic variability at the cytochrome B gene
      and the D-loop region has been used as a tool to dissect the genetic
      relationships between different breeds and populations. In this work, we analysed
      four SNP at the cytochrome B gene to infer the Asian (A1 and A2 haplotypes) or
      European (E1 and E2 haplotypes) origins of several European standard and local
      pig breeds. We found a mixture of Asian and European haplotypes in the Canarian
      Black pig (E1, A1 and A2), German Pietrain (E1, A1 and A2), Belgian Pietrain (E1,
      A1), Large White (E1 and A1) and Landrace (E1 and A1) breeds. In contrast, the
      Iberian (Guadyerbas, Ervideira, Caldeira, Campanario, Puebla and Torbiscal
      strains) and the Majorcan Black pig breeds only displayed the E1 haplotype. Our
      results show that the introgression of Chinese pig breeds affected most of the
      major European standard breeds, which harbour Asian haplotypes at diverse
      frequencies (15-56%). In contrast, isolated local Spanish breeds, such as the
      Iberian and Majorcan Black pig, only display European cytochrome B haplotypes, a
      feature that evidences that they were not crossed with other Chinese or European
      commercial populations. These findings illustrate how geographical confinement
      spared several local Spanish breeds from the extensive introgression event that
      took place during the 18th and 19th centuries in Europe.

PMID- 14713413
TI  - A first generation bovine BAC-based physical map.
AB  - A first generation clone-based physical map for the bovine genome was constructed
      combining, fluorescent double digestion fingerprinting and sequence tagged site
      (STS) marker screening. The BAC clones were selected from an Inra BAC library
      (105,984 clones) and a part of the CHORI-240 BAC library (26,500 clones). The
      contigs were anchored using the screening information for a total of 1303 markers
      (451 microsatellites, 471 genes, 127 EST, and 254 BAC ends). The final map, which
      consists of 6615 contigs assembled from 100,923 clones, will be a valuable tool
      for genomic research in ruminants, including targeted marker production,
      positional cloning or targeted sequencing of regions of specific interest.

PMID- 14713414
TI  - Estimation of the proportion of genetically unbalanced spermatozoa in the semen
      of boars carrying chromosomal rearrangements using FISH on sperm nuclei.
AB  - Many chromosomal rearrangements are detected each year in France on young boars
      candidates for reproduction. The possible use of these animals requires a good
      knowledge of the potential effect of the rearrangements on the prolificacy of
      their mates. This effect can be estimated by an accurate determination of the
      rate of unbalanced spermatozoa in the semen of boars which carry the
      rearrangements. Indeed, these spermatozoa exhibiting normal fertilizing ability
      are responsible for an early embryonic mortality, and then, for a decrease of the
      litter sizes. The "spermFISH" technique, i.e. fluorescent in situ hybridization
      on decondensed sperm heads, has been used on several occasions in Man, in this
      perspective. In livestock species, this method was formerly used mainly for semen
      sexing purposes. We used it, for the first time, to estimate the rates of
      imbalance in the semen of four boars carrying chromosomal rearrangements: two
      reciprocal translocations, rcp(3;15)(q27;q13) and rcp(12;14)(q13;q21), as well as
      two independent cases of trisomy 18 mosaicism. The rates of unbalanced gametes
      were relatively high for the two reciprocal translocations (47.83% and 24.33%,
      respectively). These values differed from the apparent effects of the
      rearrangements estimated using a limited number of litters: a decrease in
      prolificacy of 23% (estimation obtained using the results of 6 litters) and 39%
      (57 litters), respectively for the 3/15 and 12/14 translocations. The imbalance
      rates were much lower for the trisomy mosaics (0.58% and 1.13%), suggesting a
      very moderate effect of this special kind of chromosomal rearrangement.

PMID- 14713508
TI  - Consensus on anti-platelet therapy in peripheral arterial disease: saving lives
      and limbs.

PMID- 14713509
TI  - Patients with paroxysmal atrial fibrillation but not paroxysmal supraventricular
      tachycardia display evidence of platelet activation during arrhythmia.
AB  - It is well known that chronic atrial fibrillation (CAF) and paroxysmal atrial
      fibrillation (PAF) are associated with hypercoagulable state. However,
      pathological hemostatic changes during the paroxysmal supraventricular
      tachycardia (PSVT) have not yet been elucidated. To determine platelet activity
      in patients with PSVT, PAF and CAF, we examined the levels of beta
      thromboglobulin (BTG) and platelet factor 4 (PF4) during tachyarrhythmia attacks.
      We measured the levels of BTG and PF4, as an index of platelet activation in 15
      patients with PAF (9 men, mean age 45+/-11), and 14 patients with PSVT (8 men,
      mean age 40+/-10). Levels were compared to 22 age and sex matched healthy
      controls in sinus rhythm and with 25 patients with CAF (16 men, mean age 51+/
      12). Blood samples were taken during arrhythmia and 24 hours after conversion to
      sinus rhythm. Patients taking medications or have clinical conditions that may
      affect the BTG and PF4 levels were excluded. In patients with PAF, BTG and PF4
      levels were significantly higher than in controls (p<0.009, and p=0.002,
      respectively), and in patients with PSVT (p<0.004, and p=0.009, respectively),
      however, BTG and PF4 levels were significantly lower than CAF patients (p=0.002,
      and p=0.02, respectively). Moreover, BTG and PF4 levels were significantly
      decreased 24 hours after conversion to sinus rhythm (p<0.0001), and p=0.004,
      respectively). Although BTG and PF4 levels in patients with PSVT were
      significantly lower than in patients with PAF (p=0.04, and p=0.009, respectively)
      and CAF (p=0.0001, and p=0.0001, respectively), BTG and PF4 levels were similar
      to controls and did not change significantly after recovery to sinus rhythm (p=NS
      for all). These results indicate that there was no platelet activation in
      patients with PSVT during tachyarrhythmia but significantly increased platelet
      activity in PAF and CAF patients. There was a significant decrement of the
      platelet activity to a level of control subjects twenty-four hours after
      cardioversion of PAF.

PMID- 14713510
TI  - Studies of biological functions in blood cells from individuals with large
      platelets.
AB  - The present study was performed to explore differences in the expression of P
      selectin and IL-8 production of blood cells in healthy individuals with large
      size platelets (MI-families) as compared to people having normal size platelets.
      A positive correlation between LPS-induced IL-8 production per platelet in whole
      blood and mean platelet volume (MPV) was found in the large platelet group
      (R=0.74, P<0.05). When the large and normal groups were combined the correlation
      was nearly, but not quite significant (R=0.46, P<0.06). There was also a positive
      correlation between sP-selectin and MPV (R=0.42, P<0.05). Furthermore, IL-8 in
      serum was positively correlated to sP-selectin in serum (R=0.68, P<0.005). sP
      selectin baseline values in citrated plasma correlated significantly with values
      found in serum (R=0.72, P<0.0005), indicating that sP-selectin in blood
      originates from the platelets rather than from endothelial cells. Significant
      correlations were also found in both groups between P-selectin and CD40L (R=0.44,
      P<0.05) and P-selectin and RANTES (R=0.44, P<0.05). A significant correlation was
      also found between PDGF and RANTES (R=0.44, P<0.05). Our results suggest that
      larger platelets enhance the production of IL-8 more than normally sized
      platelets. This phenomenon is probably mediated through P-selectin exposed on
      platelets.

PMID- 14713511
TI  - Inhibition of human blood platelet aggregation and the stimulation of nitric
      oxide synthesis by aspirin.
AB  - Incubation of platelet-rich plasma with 80 microM aspirin that resulted in the
      inhibition of both the secondary phase of ADP induced platelet aggregation and
      prostaglandin synthesis simultaneously stimulated the production of NO in
      platelets. Furthermore it was found that the treatment of platelet-rich plasma
      either with 80 microM ibuprofen or salicylic acid, like aspirin, which inhibited
      the secondary phase of platelet aggregation by ADP and prostaglandin synthesis,
      also stimulated the production of NO in the absence of added ADP. However the
      inhibition of prostaglandin synthesis by ibuprofen or salicylic acid, unlike
      aspirin, was transient in nature. Incubation of washed platelets with any of
      these three compounds also stimulated NO synthesis indicating that the effect of
      these compounds was not mediated through plasma proteins. The in vitro effect of
      aspirin on the increase of NO in platelets could also be demonstrated by in vivo
      exposure of platelets to the compound. It was concluded that either a temporary
      or a lasting inhibition of prostaglandin synthesis by these inhibitors resulted
      in the synthesis of NO in resting platelets. Since NO is a potent inhibitor of
      platelet aggregation the inhibition of platelet aggregation, by these compounds
      may not be the consequence of the inhibition of prostaglandin synthesis alone,
      but could also be related, at least partly, to the stimulated synthesis of NO by
      these inhibitors.

PMID- 14713512
TI  - Analysis of nitric oxide-sensitive guanylyl cyclase in human platelets before and
      after aggregation.
AB  - Nitric oxide (NO) inhibits cell adhesion to vascular endothelium and platelet
      aggregation through activation of soluble guanylyl cyclase (sGC) and a consequent
      increase in cGMP. The aim of the present study was to analyze NO-sensitive sGC in
      human platelets before and after aggregation. NO-sensitive sGC activity was
      tested in the cytosol and membrane fractions of native human platelets and ADP
      induced platelet aggregates in the presence of 3 mM Mn2+ as cofactor. After ADP
      induced platelet aggregation there was a significant increase of sGC activity in
      membranes. Western blot analysis showed a partial translocation of the enzyme to
      the plasma membrane. These findings support recent data that sGC is associated
      with cellular membranes in various tissues and cell types and that this membrane
      association is influenced by the activation state in human platelets (Nat Cell
      Biol 2002; 4: 307-11). Using 3 mM Mg2+ instead of Mn2+ as cofactor, a sharp
      decrease of sGC activity was apparent in the cytosol of aggregated platelets.
      Kinetic analysis of the cytosolic enzyme and concentration-response curves for
      free Mg2+ showed that platelet aggregation changes binding of free Mg2+ but not
      binding of the substrate complex Mg.GTP. This effect was specific for free Mg2+
      and was not seen for Mn2+. In addition, changes in free Mg2+ concentration in a
      physiological range markedly influenced NO-stimulated sGC activity. This provides
      a possible explanation for the increased platelet aggregability in patients with
      low intraplatelet Mg2+ levels.

PMID- 14713513
TI  - Is primary haemostasis controlled by a 'platelet delay time'? Formulation of a
      new hypothesis.
AB  - A simple physical model is able to adequately describe platelet thrombus
      formation during primary haemostasis ex vivo, under the assumption of a 'platelet
      delay time' (Pdel), which is defined as the difference between the moment of
      platelet adhesion (to collagen or to another adherent platelet) and the time when
      the newly adherent platelet allows another platelet to adhere. Pdel was estimated
      with an ex vivo model of primary haemostasis (modified PFA-100, Dade Behring,
      Marburg). ADP and epinephrine test cartridges were perfused with human
      anticoagulated blood of control persons using a pressure/flow clamp technique
      (Kretschmer V, et al. Platelets 2001; 12: 462-9). Platelets gradually occluded
      the aperture in the test system. Pressure (p) across and flow (Q) through the
      aperture were measured versus time. The change of the aperture radius versus time
      (dr/dt) was calculated from p and Q using the Law of Hagen-Poiseuille. The
      surprising result was a constant decay of dr/dt (Rsqu approximately 0.996), in
      spite of a 5-fold increase in the shear- and transport-rates of platelets. This
      can be explained by postulating the existence of a Pdel, which was estimated as
      2.89 s for collagen/ADP and 4.62 s in collagen/epinephrine test cartridges. This
      new hypothesis explains for the first time the relative independence of in vivo
      and ex vivo bleeding time on blood platelet concentrations, a well known
      observation at platelet counts higher than 40,000/microl. If the described
      physical model is correct, platelet thrombus growth rate is strongly decreased as
      a consequence of Pdel in extreme arterial flow conditions. A preliminary report
      of these experiments has been published (Kratzer MAA, Platelets 2002; 13: 344).

PMID- 14713514
TI  - Agonist concentration-dependent differential responsivity of a human platelet
      purinergic receptor: pharmacological and kinetic studies of aggregation,
      deaggregation and shape change responses mediated by the purinergic P2Y1 receptor
      in vitro.
AB  - Platelet shape change (SC), aggregation and deaggregation responses are integral
      components of hemostasis that are elicited and modulated in vivo by the
      simultaneous activation of several membrane receptors. Selective activation of
      the purinergic P2Y1 receptor in vivo elicits a sustained SC and a small,
      transient aggregation response that is reversed rapidly by a robust deaggregation
      response (Platelets 2003; 14: 89). Using a kinetics-based turbidimetric approach
      to study the modulation of these concurrent components of human platelet
      responses, we demonstrate that these P2Y1 receptor-related responses and a number
      of their kinetic and steady-state characteristics are differentially elicited and
      modulated. P2Y1 receptor agonist concentrations that elicited aggregation (pEC50
      for ADP, 2-MeSADP; 5.88, 6.69) were 10-fold greater than those that elicited SC
      (7.33, 7.67). The magnitude of the aggregation response was agonist concentration
      dependent, saturable and was associated with an agonist concentration-dependent
      deceleration of the deaggregation response. Gi-coupled receptor (alpha 2A
      adrenoceptor, EP3 and P2Y12 receptors) agonists also enhanced aggregation through
      deceleration of the deaggregation response, and an inhibitor of PI3K activity
      (wortmannin) inhibited aggregation through acceleration of the deaggregation
      response. Neither treatment affected the extent or the kinetics of the SC
      response. The aggregation but not the SC response was rapidly desensitized by
      P2Y1 receptor activation by ADP. The affinity of the presence of a single P2Y1
      receptor subtype. The differential characteristics and modulation of the SC and
      aggregation responses by a single receptor support the idea that different
      signaling pathways activated at different occupancy states of the same receptor
      underlie the two responses. P2Y1 receptor-mediated platelet aggregation and SC
      responses provide a convenient model for studying the phenomenon of agonist
      directed signaling by differential occupancy of the same membrane receptor.

PMID- 14713515
TI  - An hypothesis on the consolidation and PGE1-induced deconsolidation of a platelet
      plug.
AB  - Consolidation is the final stage in haemostasis in which a platelet plug blocking
      a bleeding area of a vessel: (a) becomes impermeable to circulating plasma
      proteins and (b) contracts to resist blood pressure. HYPOTHESIS: The
      impermeabilization step of consolidation is accomplished through fluid uptake by
      the platelets from a hydrated intercellular glue formed during thrombin
      activation. Dehydration occurs through inhibition of the Na+,K+-ATPase of
      platelets with sodium and water uptake. However, and uniquely, due to the high
      cellular density of the platelet plug, access of peripheral plasma fluids to the
      plug is limited forcing the platelets to take up preferentially the fluid of
      interplatelet space. The increased adhesion properties of the dehydrated glue
      simultaneously furthers a decreased hydraulic permeability and an improved
      coupling of the contractile forces among platelets. In 'Deconsolidation', the
      fluid uptake process can be reversed and amplified by agents that increase cAMP,
      reactivating the Na+,K+-ATPase and expressing CFTR or equivalent Cl- secretory
      channels that force the extrusion of fluid from the platelets, with rehydration
      of the intercellular polymer and a large increase in the interplatelet space.

PMID- 14713516
TI  - P-selectin, tissue factor and CD40 ligand expression on platelet-leucocyte
      conjugates in the presence of a GPIIb/IIIa antagonist.
AB  - This study was to investigate the appearance of P-selectin, tissue factor (TF)
      and CD40 ligand (CD40L) on platelet-leucocyte conjugates in the absence and
      presence of a GPIIb/IIIa antagonist, MK-852, and the effect of adding EDTA to pre
      formed conjugates. The purpose was to find out whether these antigens are
      displaced from the conjugates along with the platelets, thus providing
      information on their location. Hirudinized blood was stirred with collagen ((2
      microg/mL) in the absence and presence of MK-852 (10 micromol/mL)). P-selectin,
      TF and CD40L were measured on platelet-leucocyte conjugates (CD42a positive
      monocytes and neutrophils) and on single platelets by flow cytometry.
      Measurements were also made after subsequent addition of EDTA (4 mmol/L).
      Platelet-leucocyte conjugate formation was markedly enhanced in the presence of
      MK-852. P-selectin, TF and CD40L expression on the conjugates was also enhanced.
      Monocytes bound more platelets and expressed more P-selectin, TF and CD40L than
      neutrophils. EDTA displaced the majority of platelets from the conjugates and
      also the P-selectin, TF and CD40L, whereas it did not displaced P-selectin or
      CD40 ligand from the platelets themselves. It is concluded that a GPIIb/IIIa
      antagonist promotes formation of platelet-leucocyte conjugates, which display P
      selectin, TF and CD40L that appears to be associated with the adherent platelets.
      Platelet-monocyte conjugates are prime candidates for arterial inflammation and
      thrombosis. Pro-inflammatory and pro-thrombotic effects of CD40L and tissue
      factor may be an explanation of the negative clinical effects using GPIIb/IIIa
      antagonists.

PMID- 14713517
TI  - A new method of representing drug-induced platelet inhibition: better description
      of time course, response variability, non-response, and heightened activity.

PMID- 14713518
TI  - A note on the platelet count in Thai vegans.

PMID- 14713541
TI  - Possible mechanisms underlying the testicular toxicity of oxfendazole in rats.
AB  - To clarify the mechanisms underlying the testicular toxicity of oxfendazole (OX),
      adult Wistar rats were orally administered a dose of 100 mg/kg/day for 3, 7, or
      14 days. Assays of sex-related hormones showed a significant decrease in only the
      estradiol serum level at days 3 and 7, as compared with the control group.
      Histopathologically, marked degeneration of meiotic spermatocytes was observed in
      stage XIV-I seminiferous tubules from day 3 onwards, and these spermatocytes gave
      positive results on terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      nick end-labeling (TUNEL). Abnormalities of spermiogenesis such as
      megakaryospermatids and binucleated spermatids were also observed in the testes
      of OX-treated rats. Under the electron microscope, lipid accumulation and
      dilatation of the endoplasmic reticulum were frequently found in the cytoplasm of
      the Sertoli cells on day 3. These results strongly suggest that OX induces both
      apoptosis of meiotic spermatocytes, most probably due to disruption of the
      microtubules, and degeneration of the Sertoli cells, characterized by distended
      endoplasmic reticulum and prominent cytosolic lipid accumulation.

PMID- 14713542
TI  - Immunohistochemical detection of activated caspases in apoptotic hepatocytes in
      rat liver.
AB  - In our study we tested the utility of antibodies that specifically recognize the
      cleaved large (active) subunits of caspase-3 and caspase-9 for
      immunohistochemical detection of apoptotic hepatocytes in rat liver sections
      using archival material from cyproterone acetate (CPA)-treated and control rats.
      CPA blocks apoptosis of hepatocytes and discontinuation of CPA treatment results
      in a syncronized wave of hepatocyte apoptosis. By comparing liver sections from
      CPA-treated and control rats with high and low rates of apoptosis we observed a
      close correlation between the occurrence of cleaved caspase-positive apoptotic
      figures and H&E-stained apoptotic bodies when evaluated in parallel sections.
      Caspase-stained figures were either immuno-positive apoptotic bodies or pre
      apoptotic hepatocytes showing cytoplasmic and/or nuclear caspase-staining with
      otherwise normal cellular appearance. In extension of these observations we
      developed a double-immunohistochemical staining procedure which enables the
      detection of caspase-3-positive apoptotic hepatocytes within glutathione-S
      transferase-P (GST-P)-positive preneoplastic liver foci. By use of this
      technique, inhibition of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin as
      detected by counting of H&E-stained apoptotic bodies was found to correlate with
      a strong reduction of cleaved caspase-positive hepatocytes in GST-P-positive
      preneoplastic foci. In summary, this study demonstrates that cleaved caspase
      positive apoptotic hepatocytes could be reliably identified and quantified both
      in normal and neoplastically transformed liver tissue.

PMID- 14713543
TI  - Predominant K-ras codon 12 G --> A transition in chemically induced lung
      neoplasms in B6C3F1 mice.
AB  - Based on long-term toxicity and carcinogenicity studies in B6C3F1 mice conducted
      by the National Toxicology Program, 2,2-Bis(bromomethyl)-1,3-propanediol (BMP)
      and tetranitromethane (TNM) have been identified as carcinogens. Following 2 yr
      of exposure to 312, 625, or 1,250 ppm BMP in feed, or exposure to 0.5 or 2 ppm
      TNM by inhalation, increased incidences of lung neoplasms were observed in B6C3F1
      mice at all exposure concentrations compared to unexposed mice. The present study
      characterizes genetic alterations in the K-ras protooncogene in BMP- and TNM
      induced lung neoplasms, respectively, and compares the findings to spontaneous
      lung neoplasms from corresponding control mice. The frequencies of the K-ras
      mutations were 57% (29/51) in BMP-induced lung neoplasms compared to 15% (3/20)
      in lung neoplasms from dosed feed control mice, and 54% (14/26) in TNM-induced
      lung neoplasms compared to 60% (3/5) in lung neoplasms from inhalation control
      mice. G --> A transitions at the second base of the K-ras codon 12 (GGT --> GAT)
      were the most frequent pattern of K-ras mutations identified in BMP-induced
      (20/29) and TNM-induced lung neoplasms (13/14), which differed from the
      mutational patterns identified in the lung neoplasms from unexposed control mice.
      These results indicate that mutations in the K-ras gene are involved in B6C3F1
      lung carcinogenesis following BMP- and TNM-exposure, and the high frequency and
      specificity of the ras mutation profile in lung neoplasms (G --> A transition)
      may be due to in vivo genotoxicity by the parent compounds or their metabolites.

PMID- 14713544
TI  - Articular chondromatosis and chrondroid metaplasia in transgenic TAg mice.
AB  - The C3(1)/SV40 T antigen transgenic mouse model for which rapid mammary and
      prostate tumor development has been documented uses the FVB/N mouse as a
      background strain. In this study, where the background strain used was the
      C57BL/6J mouse, neither mammary nor prostate tumors developed over periods of up
      to 40 weeks. However, a disturbance of hyaline cartilage in joints was observed
      similar to that found in synovial chondromatosis in humans. In addition,
      cartilage thickening in the external ears and cartilaginous metaplasia of the
      ascending aorta also occurred. This suggests that rearrangement of the transgene
      occurred in breeding on the C57BL background, thus modifying its expression. It
      raises the possibility that the genetic changes induced by the SV40 T antigen
      transforming sequence are important in cartilage homeostasis.

PMID- 14713545
TI  - Localization of satratoxin-G in Stachybotrys chartarum spores and spore-impacted
      mouse lung using immunocytochemistry.
AB  - Satratoxin-G (SG) is the major macrocyclic trichothecene mycotoxin produced by
      Stachybotrys chartarum (atra) and has been implicated as a cause of a number of
      animal and human health problems including pulmonary hemorrhage in infants.
      However, there is little understanding where this toxin is localized in the
      spores and mycelial fragments of this species or in the lung impacted by SG
      sequestered spores. The purpose of this study was to evaluate the distribution of
      SG in S. chartarum spores and mycelium in culture, and spore-impacted mouse lung
      in vivo, using immunocytochemistry. SG was localized predominately in S.
      chartarum spores with moderate labelling of the phialide-apex walls. Labelling
      was primarily along the outer plasmalemma surface and in the inner wall layer.
      Only modest labelling was observed in hyphae. Toxin localization at these sites
      supports the position that spores contain the highest satratoxin concentrations
      and that the toxin is constitutively produced. In impacted mouse lung, highest SG
      labelling was detected in lysosomes, along the inside of the nuclear membrane in
      nuclear heterochromatin and RER within alveolar macrophages. Alveolar type II
      cells also showed modest labelling of the nuclear heterochromatin and RER. There
      was no evidence that the toxin accumulated in the neutrophils, fibroblasts, or
      other cells associated with the granulomas surrounding spores or mycelial
      fragments. These observations indicate that SG displays a high degree of cellular
      specificity with respect to its uptake in mouse lung. They further indicate that
      the alveolar macrophages play an important role in the sequestration and
      immobilization of low concentrations of the toxin.

PMID- 14713546
TI  - Hexachlorobenzene-induced incisor degeneration in Sprague-Dawley rats.
AB  - Hexachlorobenzene (HCB) was administered to female Sprague-Dawley rats in a 13
      week toxicity study conducted for the National Toxicology Program (NTP). Groups
      of 10 rats were treated by gavage with 0.0, 0.03, 0.1, 0.3, 1.0, 3.0, 10, or 25
      mg/kg HCB in corn oil 5 days/week for 13 weeks. Dose-dependent, region-specific,
      maxillary incisor degeneration was observed in animals given HCB at doses of 1.0
      mg/kg/day and higher. Treatment with 1.0 mg/kg/day resulted in focal mesenchymal
      cell vacuolation and focal osteodentin formation within the pulp. Lesions were
      restricted to a short linear region subjacent to the odontoblast layer along the
      lateral aspect of the incisor at the level of the dentin-enamel interface. When
      observed in both incisors, lesions were bilaterally symmetric. Treatment with 3.0
      mg/kg/day resulted in lateral and medial pulp lesions and focal odontoblast
      degeneration with dentin niche formation along the lateral incisor margin in some
      animals. Treatment with 10 mg/kg/day resulted in a higher incidence of lateral
      dentin niches and a low incidence of medial dentin niches. In animals treated
      with 25 mg/kg/day, a high incidence of bilaterally symmetric, lateral and medial,
      dentin niches were observed. The morphology and distribution of HCB-induced
      incisor lesions in rats are consistent with injury to a selective population of
      preodontoblasts.

PMID- 14713547
TI  - Follicular epithelial cell hypertrophy induced by chronic oral administration of
      2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) affects the thyroid morphologically
      and/or functionally in adult animals. Recently, the National Toxicology Program
      conducted a 2-year gavage study of TCDD in female Harlan Sprague-Dawley rats. The
      only treatment-related alterations found in thyroid follicles were decreased
      luminal size and increased height of the follicular epithelial cells, without
      prominent protrusion into the lumen. The present study elucidated the nature of
      these follicular lesions. Thyroid glands of 10 rats each from the control, high
      (100 ng/kg/day)-dose, and stop-study (100 ng/kg/day, 30 weeks; vehicle to study
      termination) groups in the 2-year study were evaluated microscopically. Twenty
      randomly selected follicles were measured morphometrically in each animal. TCDD
      treatment significantly decreased the mean ratio of luminal/epithelial areas and
      increased the mean sectional epithelial height of the high-dose group compared to
      controls. Thyroid sections were immunostained with antibody against
      minichromosome maintenance (MCM) proteins, a novel cell-cycle biomarker. The MCM
      labeling index of the high-dose group was significantly higher than that of the
      control; however, the TUNEL labeling index was also higher in the high-dose group
      than the control. All data from the stop group were comparable to those from
      controls. These results indicate that the follicular cell response was
      hypertrophic and reversible. This information should contribute to diagnosis of
      nonneoplastic thyroid follicular lesions in rats.

PMID- 14713548
TI  - Metabolic alterations of toxic and nonessential elements by the treatment of
      Sempervivum tectorum extract in a hyperlipidemic rat model.
AB  - A hyperlipidemic rat model was used to examine the therapeutic effect of
      Sempervivum tectorum plant extract on the metabolic alterations of Al, As, B, Ba,
      Cd, Hg, Ni, Pb, and Ti in the liver and bile. Hyperlipidemia was produced by
      lipogenic diet and alcohol and verified by morphological investigation of the
      liver with the aid of light and an electron microscope. Element concentration in
      the liver and bile were determined by inductively coupled plasma optical emission
      spectrometry (ICP-OES). The concentration values in the liver higher than the
      detection limit (Al, Ba, Ni, Ti) were unambiguous. Significant differences were
      found for the four groups at p < 0.05 level (ANOVA). A significant difference was
      observed between Al and B concentration in the bile fluids of the 4 groups (p <
      0.05). The excretion of Al and Ti into the bile fluid increased significantly (p
      < 0.05). Following the administration of S. tectorum extract to rats with
      hyperlipidemia, the excretion of Al, B and Ba increased, whereas the excretion of
      Ti decreased significantly (p < 0.05). The favorable action of the extract
      (protecting the liver in hyperlipidemic rats) was verified by morphological
      studies, and its detoxicating property was shown by the elimination of Al, Ba,
      Ni, and Ti from the liver.

PMID- 14713549
TI  - Promotion of colon tumors in C57BL/6J-APC(min)/+ mice by thiazolidinedione
      PPARgamma agonists and a structurally unrelated PPARgamma agonist.
AB  - Thiazolidinedione PPARgamma agonists (troglitazone and rosiglitazone) were
      previously shown to promote colon tumor formation in C57BL/6J-APC(min)/+ mice, a
      model for human familial adenomatous polyposis. This study was conducted to
      determine if another thiazolidinedione PPARgamma agonist, pioglitazone, and a
      PPARgamma agonist structurally unrelated to the thiazolidinedione family, NID525,
      (a tetrazole-substituted phenoxymethylquinolone), would also promote colon tumors
      in this mouse model. Mice were treated in-feed with the thiazolidinediones
      troglitazone (150 mg/kg/day), rosiglitazone (20 mg/kg/day), or pioglitazone (150
      mg/kg/day), or with NID525 (150 mg/kg/day) for 8 weeks. An increased incidence in
      colon tumors compared to controls was observed for all of the thiazolidinedione
      treated groups as well as the NID525-treated group. These results indicate that
      the tumor-promoting effect of PPARgamma agonists in the colon of C57BL/6J
      APC(min)/+ mice is likely related to the pharmacological activity of this group
      of drugs and not the thiazolidinedione structure.

PMID- 14713550
TI  - Subchronic exposure to arsenic through drinking water alters expression of cancer
      related genes in rat liver.
AB  - Although arsenic exposure causes liver disease and/or hepatoma, little is known
      about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis.
      We investigated the effects of arsenic on expression of cancer-related genes in a
      rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in
      drinking water), by using real-time quantitative RT-PCR and immunohistochemical
      analyses. Arsenic accumulated in the rat liver dose-dependently and caused
      hepatic histopathological changes, such as disruption of hepatic cords,
      sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic
      significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm),
      and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta
      catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA
      expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and
      decreased expression of both PTEN and beta-catenin at all 3 doses. An
      immunohistochemical study revealed that each protein expression accords closely
      with each gene expression of mRNA level. In conclusion, subchronic exposure to
      inorganic arsenate caused pathological changes and altered expression of cyclin
      D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that
      arsenic liver toxicity involves disturbances of some cancer-related molecules.

PMID- 14713551
TI  - Boron supplementation inhibits the growth and local expression of IGF-1 in human
      prostate adenocarcinoma (LNCaP) tumors in nude mice.
AB  - Prostate-specific antigen (PSA) is a serine protease and one of the most abundant
      proteins secreted by the human prostate epithelium. PSA is used as a well
      established marker of prostate cancer. The involvement of PSA in several early
      events leading to the development of malignant prostate tumors has made it a
      target for prevention and intervention. It is thought that PSA cleaves insulin
      like growth factor binding protein-3 (IGFBP-3), providing increased local levels
      of IGF-1, leading to tumor growth. Separately, there are data that suggest an
      enzymatic regulatory role for dietary boron, which is a serine protease
      inhibitor. In this study we have addressed the use of boric acid as a PSA
      inhibitor in an animal study. We have previously reported that low concentrations
      (6 ug/mL) of boric acid can partially inhibit the proteolytic activity of
      purified PSA towards a synthetic fluorogenic substrate. Also, by Western blot we
      have followed the degradation of fibronectin by enzymatically active PSA and have
      found significant inhibition in the presence of boric acid. We proposed that
      dietary supplementation with boric acid would inhibit PSA and reduce the
      development and proliferation of prostate carcinomas in an animal model. We
      tested this hypothesis using nude mice implanted subcutaneously with LNCaP cells
      in Matrigel. Two groups (10 animals/group) were dosed with boric acid solutions
      (1.7, 9.0 mgB/kg/day) by gavage. Control group received only water. Tumor sizes
      were measured weekly for 8 weeks. Serum PSA and IGF-1 levels were determined at
      terminal sacrifice. The size of tumors was decreased in mice exposed to the low
      and high dose of boric acid by 38% and 25%, respectively. Serum PSA levels
      decreased by 88.6% and 86.4%, respectively, as compared to the control group.
      There were morphological differences between the tumors in control and boron
      dosed animals, including a significantly lower incidence of mitotic figures in
      the boron-supplemented groups. Circulating IGF-1 levels were not different among
      groups, though expression of IGF-1 in the tumors was markedly reduced by boron
      treatment, which we have shown by immunohistochemistry. These data indicate that
      low-level dietary boron supplementation reduced tumor size and content of a tumor
      trophic factor, IGF-1. This promising model is being evaluated in further
      studies.

PMID- 14713552
TI  - Male reproductive tract lesions at 6, 12, and 18 months of age following in utero
      exposure to di(n-butyl) phthalate.
AB  - In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP)
      leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased
      areolae retention on PND 13, malformations in the male reproductive tract, and
      histologic testicular lesions including marked seminiferous epithelial
      degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One
      objective of this study was to determine the incidence and persistence of
      decreased AGD, increased areolae retention, and LC adenomas in adult rats
      following in utero DBP exposure. A second objective was to determine whether AGD
      and areolae retention during the early postnatal period are associated with
      lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged
      with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates
      of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and
      the male offspring allowed to mature to 6, 12, or 18 months of age. Gross
      malformations in the male reproductive tract and histologic lesions in the testes
      were similar to those previously described. However, testicular dysgenesis, a
      lesion of proliferating LCs and aberrant tubules that has not been previously
      described in DBP-exposed testes, was diagnosed. The incidence of this lesion was
      approximately 20% unilateral and 7-18% bilateral in the high-dose group and was
      similar among all ages examined, implicating a developmental alteration rather
      than an age-related change. AGD and areolae retention were found to be permanent
      changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a
      sensitive predictor of lesions in the male reproductive tract, relatively small
      changes in AGD were associated with a significant incidence of male reproductive
      malformations. In utero DBP exposure induced proliferative developmental lesions,
      some of which would have been diagnosed as LC adenomas by the morphological
      criteria set forth by the Society of Toxicologic Pathology. However, these
      lesions were dissimilar to traditional LC adenomas as the LCs were poorly
      differentiated and the lesions contained aberrant seminiferous tubules. While the
      morphology and incidence of this DBP-induced testicular developmental lesion has
      been fully characterized by this study, the detailed pathogenesis warrants
      further investigation.

PMID- 14713553
TI  - Effects of dietary isoflavone aglycones on the reproductive tract of male and
      female mice.
AB  - We assessed the effects of dietary consumption of soy isoflavone aglycones on the
      reproductive tract of sexually mature male and female mice. Isoflavone
      concentrates with a ratio of 10:1, 2:1 or 1:10 genistein:daidzein (G:D) were
      added to provide 120 mg total isoflavones/1800 Calories (approximately 40 mg/kg
      body weight) to diets having either casein/lactalbumin or soy protein isolate as
      the source of protein. After 16 weeks, mice were necropsied and gross and
      histopathologic assessments of uterus, vagina, testes and accessory sex glands
      were completed. Effects of the 10G:1D isoflavone concentrates were absent or
      minimal in females but in males included atrophy of accessory sex glands. In
      contrast, the 2G:1D and 1G:10D concentrates caused dramatic estrogenic effects in
      both male and female mice. Effects in females included endometritis and effects
      typical of estrogenic stimulation (i.e., uterine enlargement, keratinization of
      vaginal epithelium, increased height of endometrial surface epithelial cells, and
      uterine squamous metaplasia). Effects in males included reduced plasma
      testosterone concentrations, atrophy of seminiferous epithelium, atrophy of
      accessory sex glands, and squamous metaplasia of seminal vesicles. Some effects
      varied with protein source. We conclude that a diet containing approximately 40
      mg/kg soy isoflavone aglycones with a genistein:daidzein ratio of 2:1 or less has
      marked estrogenic effects on the reproductive system of male and female mice.

PMID- 14713554
TI  - Zonal distribution of cell proliferation in the liver of untreated B6C3F1 and
      C57BL mice.
AB  - To determine the lobular distribution of hepatocellular proliferation, S-phase
      response was measured in untreated adult male B6C3F1 and C57BL mice at ages 11,
      14, and 23 weeks. The percentage of cells in S-phase (labeling index, LI) was
      evaluated using immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU).
      The BrdU was delivered either by a single ip injection 2 hr prior to sacrifice or
      via an osmotic minipump implanted subcutaneously for 3 or 7 days. Mitotic and
      apoptotic indices were determined on H&E stained sections. Animals of both
      strains and all ages revealed highest LI in the intermediate compartment of the
      liver acinus (zone 2) irrespective of the length of BrdU application. Cell
      proliferation in this zone was at all time points significantly higher than
      elsewhere in the liver. The mitotic index confirmed the data obtained by the S
      phase response study. Apoptosis was rarely observed. With regard to rodent data
      in chemical carcinogenesis and the way they should be evaluated, this study
      proved that the acinar distribution of proliferating cells in liver of mice is
      different from that in rats, since, according to the literature, rats reveal
      highest cell proliferative activity in the periportal zone.

PMID- 14713555
TI  - Serum troponins as biomarkers of drug-induced cardiac toxicity.

PMID- 14713556
TI  - Society of Toxicologic Pathology position on histopathology data collection and
      audit trail: compliance with 21 CFR parts 58 and 11.
AB  - The purpose of this paper is to discuss the requirement of the audit trail to
      track changes made to the histopathology data, in order to be compliant with the
      Code of Federal Regulations (CFR), Volume 21, for both Part 58 (Good Laboratory
      Practices [GLP]) and Part 11 (Electronic Records/Signatures).

PMID- 14713557
TI  - Society of toxicologic pathology position on assessment of hyperplastic lesions
      in rodent carcinogenicity studies.

PMID- 14713558
TI  - Best practices guideline: toxicologic histopathology.

PMID- 14713561
TI  - Efficiency in removing pollutants by constructed wetland purification systems in
      Poland.
AB  - The aim of this study was to compare the efficiency between Phragmites communis,
      Salix viminalis, and Populus canadensis in removing the heavy metals Al, Ba, Mn,
      Ni, Sr, V, Zn, Cd, Cu, and Pb and the eutrophying macroelements phosphate,
      nitrate, nitrite, ammonia, chloride, sulfate, Ca, Mg, K, and Fe from sewage in
      subsurface flow constructed wetlands in Poland. The effectiveness of the sewage
      treatment system was higher in summer compared to winter for the removal of (1)
      all heavy metals, phosphate (P) and mineral nitrogen (N) for all of species, (2)
      sulfates (S) for Phragmites and Salix, (3) iron (Fe) for Salix, and (4) chloride
      (Cl) for Salix and Populus. Analysis of variance indicated that there was no
      significant difference between the purifications systems in phytoremediation of
      Mn; so all species were equally effective (99%, prob. level 0.001). The Salix
      wetland system was most effective in purification of water and removal of
      macroelements (24-82% in summer, 10-80% in winter with Fe 97%), Cd (58-71%), V
      (100%), and Zn (84-92%). The Phragmites system was most effective in purification
      and removal of Al (81-97%), Ba (70-95%), Pb (64-81%), and Sr (24-51%), while in
      the case of Cu (49-60%) and Ni (55-67%) the Populus wetland system proved most
      effective. The outflowing water of the wetlands contained elements in amounts
      exceeding the admissible levels as established for unpolluted water both in
      winter and summer. Therefore the effectiveness of the observed phytoremediation
      systems in this study was not sufficient alone to remove these elements and can
      be considered as a supplemental tool in purification of sewage.

PMID- 14713562
TI  - Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow
      up.
AB  - Medical surveillance of a group of U.S. Gulf War veterans who were victims of
      depleted uranium (DU) "friendly fire" has been carried out since the early 1990s.
      Findings to date reveal a persistent elevation of urine uranium, more than 10 yr
      after exposure, in those veterans with retained shrapnel fragments. The excretion
      is presumably from ongoing mobilization of DU from fragments oxidizing in situ.
      Other clinical outcomes related to urine uranium measures have revealed few
      abnormalities. Renal function is normal despite the kidney's expected involvement
      as the "critical" target organ of uranium toxicity. Subtle perturbations in some
      proximal tubular parameters may suggest early although not clinically significant
      effects of uranium exposure. A mixed picture of genotoxic outcomes is also
      observed, including an association of hypoxanthine-guanine phosphoribosyl
      transferase (HPRT) mutation frequency with high urine uranium levels. Findings
      observed in this chronically exposed cohort offer guidance for predicting future
      health effects in other potentially exposed populations and provide helpful data
      for hazard communication for future deployed personnel.

PMID- 14713563
TI  - Physiologically based pharmacokinetic (PBPK) modeling of caffeine and
      theophylline in neonates and adults: implications for assessing children's risks
      from environmental agents.
AB  - Children's risks can differ from those in adults for numerous reasons, one being
      differences in the pharmacokinetic handling of chemicals. Immature metabolism and
      a variety of other factors in neonates can affect chemical disposition and
      clearance. These factors can be incorporated into physiologically based
      pharmacokinetic (PBPK) models that simulate the fate of environmental toxicants
      in both children and adults. PBPK models are most informative when supported by
      empirical data, but typically pediatric pharmacokinetic data for toxicants are
      not available. In contrast, pharmacokinetic data in children are readily
      available for therapeutic drugs. The current analysis utilizes data for caffeine
      and theophylline, closely related xanthines that are both cytochrome P-450 (CYP)
      1A2 substrates, in developing PBPK models for neonates and adults. Model
      development involved scale-up of in vitro metabolic parameters to whole liver and
      adjusting metabolic function for the ontological pattern of CYP1A2 and other
      CYPs. Model runs were able to simulate the large differences in half-life and
      clearance between neonates and adults. Further, the models were able to reproduce
      the faster metabolic clearance of theophylline relative to caffeine in neonates.
      This differential between xanthines was found to be due primarily to an extra
      metabolic pathway available to theophylline, back-methylation to caffeine, that
      is not available to caffeine itself. This pathway is not observed in adults
      exemplifying the importance of secondary or novel routes of metabolism in the
      immature liver. Greater CYP2E1 metabolism of theophylline relative to caffeine in
      neonates also occurs. Neonatal PBPK models developed for these drugs may be
      adapted to other CYP1A2 substrates (e.g., arylamine toxicants). A stepwise
      approach for modeling environmental toxicants in children is proposed.

PMID- 14713564
TI  - Neurological deficits induced by malathion, DEET, and permethrin, alone or in
      combination in adult rats.
AB  - Malathion (O,O-dimethyl-S-[1,2-carbethoxyethyl]phosphorodithionate), DEET (N,N
      diethyl-m-toluamide), and permethrin [(+/-)-cis/trans-3-(2,2-dichloroethenyl)-2,2
      dimethylcyclopropane carboxylic acid (3-phenoxyphenyl) methyl ester] are commonly
      used pesticides. To determine the effects of the dermal application of these
      chemicals, alone or in combination, the sensorimotor behavior, central
      cholinergic system, and histopathological alterations were studied in adult male
      Sprague-Dawley rats following a daily dermal dose of 44.4 mg/kg malathion, 40
      mg/kg DEET, and 0.13 mg/kg permethrin, alone and in combination for 30 d.
      Neurobehavioral evaluations of sensorimotor functions included beam-walking
      score, beam walk time, inclined plane, and grip response assessments. Twenty-four
      hours after the last treatment with each chemical alone or in combination all
      behavioral measures were impaired. The combination of DEET and permethrin,
      malathion and permethrin, or the three chemicals together resulted in greater
      impairments in inclined performance than permethrin alone. Only animals treated
      with a combination of DEET and malathion or with DEET and permethrin exhibited
      significant increases in plasma butyrlcholinesterase (BChE) activity. Treatment
      with DEET or permethrin alone, malathion and permethrin, or DEET and permethrin
      produced significant increases in cortical acetylcholinesterase (AChE) activity.
      Combinations of malathion and permethrin or of DEET and permethrin produced
      significant decreases in midbrain AChE activity. Animals treated with DEET alone
      exhibited a significant increase in cortical m2 muscarinic ACh receptor binding.
      Quantification of neuron density in the dentate gyrus, CA1 and CA3 subfields of
      the hippocampus, midbrain, brainstem, and cerebellum revealed significant
      reductions in the density of surviving neurons with various treatments. These
      results suggest that exposure to real-life doses of malathion, DEET, and
      permethrin, alone or in combination, produce no overt signs of neurotoxicity but
      induce significant neurobehavioral deficits and neuronal degeneration in brain.

PMID- 14713565
TI  - Inhibitory effects of ochratoxin A on nerve growth factor-induced neurite
      extension through downregulation of p38 MAP kinase and AP-1 activation in
      cultured pheochromocytoma cells.
AB  - Ochratoxin A (OTA) induces microcephaly in animals and in vitro cultured whole
      embryos. Inhibition of neuronal cell differentiation was proposed as underlying
      mechanisms responsible for OTA-induced microcephaly. Previously it was found that
      OTA inhibited differentiation of cultured rat embryonic midbrain cells into
      neurons. In this study, the influence of OTA on differentiation in PC-12 cells, a
      widely accepted model cells for study of neuronal differentiation was examined.
      Cell differentiation was assessed by measurement of neurite extension and
      quantified by the number of neurites extended. OTA decreased serum and nerve
      growth factor (NGF)-induced neurite extension in a concentration-dependent
      manner. Since MAP kinase and transcription factors have been implicated in cell
      differentiation of neuronal cells, and our previous study demonstrated that p38
      MAP kinase and AP-1 are activated during PC 12 cell differentiation, the effect
      of OTA on NGF-induced p38 MAP kinase and transcription factor activation was
      examined. Co-treatment of OTA with NGF resulted in inhibition of NGF-induced p38
      MAP kinase and AP-1 activation. Moreover, SB203580, a specific inhibitor of p38
      MAP kinase blocked p38 MAP kinase and AP-1 activation accompanied by further
      inhibition of neurite extension. The present study shows that OTA inhibited cell
      differentiation of PC-12 cells, and this inhibitory effect may be related to
      inhibition of the activation of the p38 MAP kinase in conjunction with
      transcription factors AP-1. This finding suggests that the inhibitory effect on
      neuronal cell differentiation by OTA might be a mechanism responsible for OTA
      induced microcephaly.

PMID- 14713566
TI  - Preventing postnatal depression: a review of research findings.
AB  - Postnatal depression is a major source of morbidity among women who have recently
      delivered a child. Considering its high prevalence and serious negative
      consequences, prevention should be a high priority. A comprehensive synthesis of
      current knowledge of prevention strategies is important for clinical practice and
      future research. Searches of MEDLINE and PsychINFO were performed to identify
      English-language articles of randomized, controlled trials published from 1990 to
      2003 focusing on primary prevention of postnatal depression in both the general
      and high-risk populations. Nineteen studies meeting these criteria were
      identified. The main findings and limitations of each study are documented. While
      the results are mixed, several of the studies provide support for the role of
      midwife intervention for pregnant and postnatal women. There are also some data
      that support the efficacy of brief psychotherapy in primary prevention.
      Unfortunately, many of the studies suffer from shortcomings that may limit their
      generalizability. Data is also lacking on biological interventions. Directions
      for future research are discussed, and general recommendations for prevention of
      postnatal depression in clinical practice are made. The findings of this review
      indicate that despite the relatively brief history of work in this area, progress
      is being made in identifying possible prevention interventions.

PMID- 14713567
TI  - Boys will be boys: fathers' perspectives on ADHD symptoms, diagnosis, and drug
      treatment.
AB  - Fathers tend to be largely absent from research and clinical settings related to
      attention-deficit/hyperactivity disorder (ADHD), as well as from public forums
      related to ADHD, such as educational conferences and parent support groups.
      Because of these absences, little is known about fathers' perspectives on ADHD
      symptoms, diagnosis, and drug treatment. This article presents findings from a
      qualitative study involving 39 mothers and 22 fathers of boys with ADHD. In-depth
      interviews were conducted with participants using a picture-based method that
      elicited detailed narratives. Results of this study suggest that fathers'
      perspectives on ADHD behaviors, diagnosis, and drug treatment can be categorized
      along two dimensions: "reluctant believers" and "tolerant nonbelievers." Across
      these two dimensions, several related factors are relevant to fathers'
      perspectives: resistance to a medical framework for understanding their sons'
      behaviors; identification with the sons' symptomatic behaviors; and resistance to
      drug treatment with stimulants. These factors may help to explain, in turn,
      fathers' absences from clinical evaluations of their sons' behaviors. The study
      affirms the importance of fathers' perspectives to the clinical evaluation and
      treatment of boys' symptomatic behaviors.

PMID- 14713568
TI  - Biochemical alterations of erythrocytes as an indicator of mental disorders: an
      overview.
AB  - During the last twenty years, numerous biochemical aberrations in red blood cells
      of subjects suffering from various mental disturbances have been detected. Red
      blood cell abnormalities observed so far include changes in the activity of some
      membrane-bound enzymes and receptors, different levels of oxidative stress, and
      differences in the lipid composition and structure of the cell membrane. Some of
      these aberrations were observed in first-episode mentally ill patients, and
      correlate well with the severity of symptoms. They suggest the existence, even at
      the onset of illness, of general cell membrane alterations, which are believed to
      play a crucial role in the receptor-mediated transduction of neurotransmitters.
      We review biochemical and physical changes of the erythrocyte membrane occurring
      in the main mental disorders--schizophrenia, depression, and bipolar disorder-
      and discuss their pertinence to the "membrane theory of schizophrenia." We also
      discuss the possibility of using erythrocyte aberrations as potential additional
      tools in the diagnosis of psychiatric diseases.

PMID- 14713569
TI  - Patients' rights and psychiatrists' duties: discharging patients against medical
      advice.
AB  - Every psychiatrist who treats voluntary inpatients has had or will have patients
      who leave the hospital against medical advice (AMA). Studies reveal that between
      6 and 35 percent of voluntary psychiatric inpatients are discharged AMA. These
      patients often are acutely ill and have severe symptoms at discharge. They also,
      as a group, have high rehospitalization rates and worse outcomes than patients
      who do not leave AMA. When a mentally ill patient demands to leave the hospital
      AMA, a tension arises between the patient's rights and the psychiatrist's duties.
      These duties include those to the patient and, in many cases, to third parties.
      Patients discharged AMA may remain dangerous and can expose health care providers
      to a heightened liability risk. More importantly, because of such factors,
      decisions about handling the AMA discharge are more difficult than decisions
      about admission. This article analyzes the sources of increased liability risk
      posed by AMA discharges. It includes discussions of patients' rights, including
      the different types of voluntary admissions, and psychiatrists' duties.
      Malpractice litigation in this area is reviewed. The article concludes by
      suggesting risk-management techniques that can aid in protecting the psychiatrist
      while also respecting patients' rights and delivering good clinical care.

PMID- 14713570
TI  - Nothing new under the sun: clozapine rechallenge following a life-threatening
      medical event in a patient with psychiatric illness and developmental disability.

PMID- 14713571
TI  - Reasons to reconsider the significance of apoptosis for cancer therapy.
AB  - In recent years, the significance of apoptosis as a process in cell loss from
      normal tissue and tumours has been critically reviewed. In addition, the general
      lack of a correlation between radiation or drug-induced apoptosis and cell
      survival responses (using the clonogenic assay) in tumour cells has been
      demonstrated. Several different reasons have been discussed by other authors. It
      is the purpose of this review to argue that there are many different forms of
      cell death (terminal differentiation, micronucleation, mitotic catastrophe or
      multinucleation) that, like apoptosis, are regulated by the cell. In this
      context, apoptosis was the first cell death mechanism associated with active
      involvement of the cell (signal transduction). Furthermore, a large variety of
      different in vitro and a few in vivo models published so far show that the form
      of cell death can shift from, for example, mitotic catastrophe to apoptosis. The
      shift appears to be a general principle and depends on the cell model examined,
      the stressor type and the stressor intensity. These considerations help to
      explain the absence of a simple link between apoptosis and clonogenicity and
      suggest how to overcome that limitation, which has implications for the
      significance of apoptosis where the diagnosis and prognosis of cancer are
      concerned.

PMID- 14713572
TI  - X-irradiated human lymphocytes with unstable aberrations and their preferential
      elimination by p53/survivin-dependent apoptosis.
AB  - PURPOSE: To investigate whether unstable types of chromosomal aberrations are
      more effective in priming apoptotic cell death in comparison with stable ones.
      Also, to highlight the phase of the cell cycle at which apoptosis occurs and the
      mechanism of its execution. MATERIALS AND METHODS: G0 human peripheral blood
      lymphocytes were X-irradiated in the presence or absence of the repair inhibitor
      cytosine arabinoside (Ara-C). After irradiation, the lymphocytes were analysed
      for induction of dicentrics, translocations, apoptosis, p53 and survivin
      expression at various recovery times. RESULTS: A preferential elimination of
      cells bearing dicentrics with respect to those with balanced translocations was
      observed. There was a time-dependent correlation between the decrease in the
      frequency of dicentrics and the increase in the per cent of apoptotic cells. Most
      of the apoptotic cells were labelled with bromodeoxyuridine and were
      mononucleated in cytochalasin B-treated cells cultures (blocked cytokinesis).
      However, after continuous colcemid treatment, the apoptotic pathway was not
      induced. Moreover, in the G2/M-phase, an increase in p53 and a decrease in
      survivin occurred that were X-ray and Ara-C dose dependent. CONCLUSIONS: The
      apoptotic process is primed when the dicentric-bearing human peripheral blood
      lymphocytes attempt to exit from metaphase. It is possible that unstable
      aberrations generate changes in the mitotic spindle causing mechanical tension at
      the kinetochore, activating the mitotic checkpoint and the execution of
      p53/survivin-dependent apoptosis.

PMID- 14713573
TI  - Low dose ionizing radiation-induced activation of connexin 43 expression.
AB  - PURPOSE: Connexin 43 has been implicated in the cellular response to ionizing
      radiation by enabling cell-to-cell communication. It is established here that the
      expression of connexin 43 is affected by ionizing radiation and the mechanism
      involved is investigated. MATERIALS AND METHODS: The human connexin 43 promoter
      was cloned into a Luciferase reporter plasmid and activation by ionizing
      radiation was measured in normal human fibroblasts as well as HeLa cells. The
      regions responsible for the radiation inducibility were defined using deletion
      and point mutations of the construct. The results were confirmed by Northern and
      Western blotting. RESULTS: Ionizing radiation activates the human connexin 43
      promoter in a time- and dose-dependent manner with a maximal induction (4.2-fold
      +/-0.58) after 6 h and a dose of 0.5 Gy. Higher doses up to 5 Gy led to a less
      marked increase (2-fold) over the same period. This promoter activation was
      associated with comparable increases in both connexin 43 mRNA and protein levels.
      The low dose radiation response of the promoter is mainly dependent on consensus
      binding sites for nuclear factor of activated T-cells (NFAT) and activator
      protein (AP1) in a region -2537 and -2110 bp from the transcriptional start site
      as determined by mutation analysis. CONCLUSIONS: Low doses of ionizing radiation
      induce the transcriptional upregulation of connexin 43 expression employing NFAT
      and AP1 sites.

PMID- 14713574
TI  - Difference in the induction, but not in the repair, of X-ray- and nitrogen ion
      induced DNA single-strand breaks as measured using human cell extracts.
AB  - PURPOSE: To compare the repair efficiency of X-ray (low linear energy transfer
      [LET]) and nitrogen ion (high LET)-induced single-strand breaks (SSB) in a human
      cell-free end-joining system. MATERIALS AND METHODS: SSB were introduced into a
      bacterial plasmid, pBR322, by X-rays (4 MeV photons) and nitrogen ions with an
      LET=125 keV micro m(-1). Repair efficiency was studied under incubation with the
      protein extracts from human squamous carcinoma cells, UT-SCC-5. RESULTS: A
      several fold higher dose of nitrogen ion radiation compared with X-ray radiation
      was needed to induce a similar loss of supercoiled plasmid DNA. There was no
      difference in the repair efficiency of SSB induced by these two types of
      radiation. CONCLUSION: The data indicate that X-rays at 25 Gy and nitroging ions
      at 100 Gy radiation doses, under condition of low scavenging capacity (10 mM
      Tris), induce SSB of similar complexity or, alternatively, differences in SSB
      complexity do not alter the repair rate.

PMID- 14713575
TI  - Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation.
AB  - PURPOSE: The effects of the heat shock protein 90 (Hsp90) inhibitor geldanamycin
      (GA) were examined on the radiosensitivity and signal transduction pathways in
      human tumour cell lines. MATERIALS AND METHODS: Two human cell lines, SQ-5 and
      DLD-1, derived from lung carcinoma and colon adenocarcinoma, respectively, were
      incubated for 16 h at 37 degrees C in medium containing 0.2 microM GA. The cells
      were then irradiated with X-rays and incubated with GA for a further 8 h.
      Radiation sensitivity was determined by clonogenic assays and protein levels were
      examined by Western blotting. RESULTS: GA radiosensitized both cell lines, but
      potentiated X-ray sensitivity more in SQ-5 than in DLD-1 cells. It was found that
      GA depleted EGFR and ErbB-2 in DLD-1 cells and depleted only ErbB-2 in SQ-5
      cells. GA also reduced the expression of Akt and phosphorylated Akt (pAkt)
      expression in SQ-5 cells. In addition, the ratio (%) of apoptotic cells and poly
      [ADP-ribose] polymerase cleavage increased in SQ-5 but not in DLD-1 cells after
      exposure to GA and X-ray irradiation. The findings suggest that GA enhances the
      radiation sensitivity of human tumour cells by inhibiting the EGFR signal
      transduction system and the Akt signalling pathway. CONCLUSION: Targeting Hsp90
      with GA provides a promising experimental strategy for radiosensitization of
      carcinoma.

PMID- 14713576
TI  - CRABP I expression and the mediation of the sensitivity of human tumour cells to
      retinoic acid and irradiation.
AB  - PURPOSE: To examine the role cytoplasmic retinoic acid binding protein type 1
      (CRABP I) and retinoic acid receptor beta 2 (RAR-beta 2) in mediating
      radiosensitization of human tumour cells in vitro by retinoic acid. MATERIALS AND
      METHODS: Human squamous cell carcinoma cell lines of different types were treated
      with retinoic acid followed by irradiation. Radiation response under drug
      treatment was detected by colony-formation assay. mRNA and protein expression
      levels of CRABP I, RAR-beta and cyclin D1 were investigated under different
      treatment conditions by room temperature polymerase chain reaction and Western
      blotting. The retinoic acid-sensitive cell line HTB35 was transfected for
      inducible CRABP I overexpression to test the role of this protein in modulating
      the sensitivity to retinoic acid and radiation as well as in regulating RAR-beta
      2 and cyclin D1 expression. RESULTS: The basal CRABP I level clearly correlated
      with the clonogenic survival of tumour cells and normal fibroblasts after
      treatment with retinoic acid and ionizing irradiation (IR). Cells expressing high
      basal CRABP I were more resistant to combined retinoic acid radiation treatment
      than cells with low basal expression. Overexpression of CRABP I in retinoic acid
      sensitive HTB35 cells induced a retinoic acid-insensitive phenotype resistant to
      combined treatment with retinoic acid and radiation. This effect was independent
      of RAR-beta 2 expression. CRABP I overexpression resulted in stimulated cyclin D1
      expression indicating the dependency of this cell cycle control protein on
      retinoic acid metabolism. CONCLUSION: CRABP I plays an important role not only in
      mediating the retinoid effects, but also in modulating the radiation sensitivity
      of tumour cells after combined retinoic acid radiation treatment.

PMID- 14713577
TI  - Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant
      induced arthritis in rats.
AB  - PURPOSE: Low-dose radiotherapy (LD-RT) of arthritic joints applied during the
      peak of the acute inflammatory response improves the clinical and
      histomorphological development of adjuvant arthritis. The study was undertaken to
      investigate the cellular composition of the inflammatory infiltrate and the
      expression of the pro-inflammatory and anti-inflammatory enzymes, inducible
      nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2) and haem-oxygenase 1 (HO
      1), in response to LD-RT. MATERIALS AND METHODS: Adjuvant arthritis in female
      Lewis rats was induced by intradermal injection of heat-inactivated mycobacterium
      tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or
      X-irradiated with either 5 x 1.0 Gy (group 2) or 5 x 0.5 Gy (group 3) from days
      15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and
      30 (n=18 joints/group), cryostat sections were analysed histologically and
      immunohistologically after specific staining for macrophages, iNOS, COX-2 and HO
      1. RESULTS: A total of 5 x 1.0 Gy or 5 x 0.5 Gy led to a significant reduction of
      clinical symptoms from days 21 to 29, and a highly significant reduction of
      cartilage and bone destruction on day 30. Macrophage-positive areas could be
      detected continuously throughout the periarticular infiltrate, and were slightly
      reduced after LD-RT on days 21 and 30. This reduction was more pronounced after 5
      x 1.0 Gy. Following LD-RT, the iNOS score was reduced by about 45-50% on days 21
      (p<0.05) and 30 (p<0.001). In contrast, the HO-1 score was increased by about 50%
      on days 21 (p=0.08) and 30 (p=0.03). CONCLUSIONS: The clinically and
      histologically observed prevention of the progression of adjuvant arthritis after
      LD-RT given during the peak of the acute inflammatory response and the reduction
      of cartilage and bone destruction in the chronic phase appears to be related to
      the modulation of iNOS activity by low X-ray doses.

PMID- 14713578
TI  - Radioresistance of sibling Drosophila species from Laguna Verde, Veracruz,
      Mexico.
AB  - PURPOSE: To identify and quantify if the generation of electricity by nuclear
      power plants produces an increase in background radiation that might affect the
      radioresistance of organisms that live in that area. MATERIALS AND METHODS:
      Natural populations of two sibling species of Drosophila, D. melanogaster and D.
      simulans, living in the immediate vicinity of the Mexican Nuclear Power Plant in
      Laguna Verde were studied for 10 years. Collections of flies were made at two
      sites, one close to and one further from two reactors, during both the pre
      operational and operational stages of the reactors. The effect of exposure to
      various doses of gamma-rays on egg-to-adult survival of the flies was analysed.
      RESULTS: The data obtained indicate that in both sites, egg-to-adult survival was
      higher in D. melanogaster than in D. simulans. There was an increase in the egg
      to-adult survival during the pre-operational period of one of the reactors and
      the possible causes are discussed. No differences were found between the two
      sites. CONCLUSIONS: The analysis indicates that the reactors do not have a
      negative impact on the Drosophila populations studied.

PMID- 14713580
TI  - Conservative treatment of scoliosis.

PMID- 14713581
TI  - The classification of spinal deformities.
AB  - Any methods of classification of scoliosis deformity devised should recognise
      different aetiological and pathological causes of the conditions and their likely
      impact on the natural history of the spinal curvature. Such classification should
      aim to aid clinicians in their approach to treatment. Furthermore, any such
      system must have a high reliability and validity. Several approaches have been
      reported. Pathological classifications have been devised which relate to the
      system or tissue affected by the underlying pathology, such as congenital
      anomalies which affect the skeletal elements of the spine, general neurological
      problems or muscular disorders. Classification by age of onset has also been
      adopted, using criteria such as infancy or adolescence. However, most attention
      has been focussed on structural features of the spine in developing anatomical
      classifications. Features such as the apex or magnitude of a curvature or its
      rotation are important clinical signs and are widely used in surgical practice.
      This paper reviews the different classification reported but make no attempt to
      justify one as being ideal. However, since the biological processes contributing
      to the deformity and its subsequent natural history are still unclear, it remains
      difficult to develop a fully reliable and all embracing system of classification.

PMID- 14713582
TI  - Aetiology of idiopathic scoliosis: current concepts.
AB  - The aetiology of the three-dimensional spinal deformity of idiopathic scoliosis
      (IS) is unknown. Progressive adolescent idiopathic scoliosis (AIS) that mainly
      affects girls is generally attributed to relative anterior spinal overgrowth from
      a mechanical mechanism (torsion) during the adolescent growth spurt. Established
      biological risk factors to AIS are growth velocity and potential residual spinal
      growth assessed by maturity indicators. Spine slenderness and ectomorphy in girls
      are thought to be risk factors for AIS. Claimed biomechanical susceptibilities
      are (1) a fixed lordotic area and hypokyphosis and (2) concave periapical rib
      overgrowth. MRI has revealed neuroanatomical abnormalities in approximately 20%
      of younger children with IS. A neuromuscular cause for AIS is probable but not
      established. Possible susceptibilities to AIS in tissues relate to muscles,
      ligaments, discs, skeletal proportions and asymmetries, the latter also affecting
      soft tissues (e.g. dermatoglyphics). AIS is generally considered to be multi
      factorial in origin. The many anomalies detected, particularly left-right
      asymmetries, have led to spatiotemporal aetiologic concepts involving chronomics
      and the genome altered by nurture without the necessity for a disease process.
      Genetic susceptibilities defined in twins are being evaluated in family studies;
      polymorphisms in the oestrogen receptor gene are associated with curve severity.
      A neurodevelopmental concept is outlined for the aetiology of progressive AIS.
      This concept involves lipid peroxidation and, if substantiated, has initial
      therapeutic potential by dietary anti-oxidants. Growth saltations have not been
      evaluated in IS.

PMID- 14713583
TI  - The use of exercises in the treatment of scoliosis: an evidence-based critical
      review of the literature.
AB  - The loss of flexibility in a spinal curvature defines it as a structural spinal
      deformity; a curvature sufficiently mobile to resolve with a change in posture is
      a non-structural or 'functional' scoliosis which is within the normal limits of
      movement for a human spine. It, therefore, seems logical that exercise-based
      therapies designed to improve and/or maintain flexibility and range of motion of
      the spine and thorax would be useful in the treatment of scoliosis. Recognition
      of the importance of maintaining flexibility of the thoracic spinal column to
      avoid scoliosis-associated pulmonary dysfunction made the use of exercise-based
      therapies a topic of clinical interest in ancient Greece. In recent years,
      successful prevention of polio epidemics has resulted in a stable change in
      patient populations such that most individuals diagnosed with scoliosis do not
      suffer from irreversible central nervous system compromise. As a result,
      realistic opportunities to examine the role of exercise in treatment of scoliosis
      are available for the first time in history. A growing body of evidence from
      independent sources is consistent with the hypothesis that exercise-based
      approaches can be used effectively to reverse the signs and symptoms of spinal
      deformity and to prevent progression in children and adults.

PMID- 14713584
TI  - Rehabilitation of adolescent patients with scoliosis--what do we know? A review
      of the literature.
AB  - Different opinions exist about the efficacy of conservative scoliosis treatment.
      Because this divergence of opinion corresponds to a great variety of standards
      applied, it is also not surprising that the results of conservative treatment
      differ a lot. Scoliosis normally does not have such dramatic effects that
      immediate surgery would be indicated. Moreover, it is clear that functional and
      physiological impairments of scoliosis patients--including pain, torso deformity,
      psychological disturbance and pulmonary dysfunction--require therapeutic
      intervention. The triad of out-patient physiotherapy, intensive in-patient
      rehabilitation and bracing has proven effective in conservative scoliosis
      treatment in central Europe. Indication, content and results of the individual
      treatment procedures are described and discussed. The positive outcomes of this
      practice validate a policy of offering conservative treatment as an alternative
      to scoliosis patients, including those for whom surgery is discussed.

PMID- 14713585
TI  - Radiological and cosmetic improvement 2 years after brace weaning--a case report.
AB  - In the early international literature, up to now only very few cases are reported
      with adolescent idiopathic scoliosis (AIS) and a significant improvement of Cobb
      angle after conservative management. In the recent literature the possibility of
      an improvement of Cobb angle at skeletal maturity after brace treatment is
      mentioned no more. The application of physiotherapy and braces is widely rejected
      while the standards of conservative measures differ greatly worldwide. So it
      seems necessary more than ever to present the possibility of successful
      conservative measures nowadays. More detailed case reports with long-term follow
      up using defined protocols are needed to provide appropriate standards for
      replication by others. The purpose of this presentation is to demonstrate the
      possibility of significant improvement of curvature angle and cosmesis after the
      application of long-term physiotherapy and brace treatment in a girl with a curve
      of more than 50 degrees where spontaneous resolving is not usual. A pre
      menarchial girl (although being Risser 2) with a Cobb angle of 53 degrees was
      treated by exercises and curve-specific bracing for more than 3 years. Two years
      after the start of the weaning period, the Cobb angle was 36 degrees with a
      marked and stable cosmetic improvement at the age of 18 years. This case report
      shows that conservative treatment can improve both cosmesis and curvature in
      immature patients with AIS. The results of such treatment is appreciated by the
      patients because of the significant reduction of the truncal deformity as
      documented by surface topography.

PMID- 14713586
TI  - Estimating the final outcome of brace treatment for idiopathic thoracic scoliosis
      at 6-month follow-up.
AB  - OBJECTIVE: The study was conducted on the possibility of predicting the final
      outcome of bracing for idiopathic scoliosis at a follow-up period of 6 months.
      METHODS: In a retrospective study, 62 adolescent female patients with right
      thoracic scoliosis (20-40 degrees Cobb angle) treated with a brace were examined.
      A new compliance score was developed. The sample was divided into four groups
      based on compliance (compliance score) and initial correction (half-year after
      start bracing): group A, good compliance/high initial correction; group B, good
      compliance/low initial correction; group C, bad compliance/high initial
      correction; group D, bad compliance/low initial correction. The final outcome (1
      year after weaning) was defined as successful if a curve correction of at least 5
      degrees was achieved. The influence of factors on final outcome was analysed by
      ANOVA. Differences between continuous data were analysed by a two-sample Wilcoxon
      test. RESULTS: The overall final outcome was not successful (thoracic curve -3
      degrees). However, the average outcome of the compliant group was successful (-5
      degrees), while no success was achieved without good compliance (+5 degrees).
      High initial correction of more than 40% (p < 0.002) and good compliance (p<
      0.004) were of significant impact for the outcome. Patients showing good
      compliance and high initial correction presented a successful outcome of 7
      degrees Cobb angle. CONCLUSION: Compliant patients with a high initial correction
      can expect a final correction of around 7 degrees, while compliant patients with
      low initial correction may maintain the curve extent. Bad compliance is always
      associated with curve progression.

PMID- 14713587
TI  - Effect of conservative management on the prevalence of surgery in patients with
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective analysis of outcome in terms of prevalence of surgery
      for adolescent idiopathic scoliosis in patients receiving conservative
      management. OBJECTIVES: To determine whether a centre with an active policy of
      conservative management has fewer patients who eventually undergo surgery for
      adolescent idiopathic scoliosis than a centre where the practice is non
      intervention. BACKGROUND DATA: The efficacy of orthoses for the treatment of
      idiopathic scoliosis was called into question in a recent publication. Because
      the prevalence of surgery in an untreated group of patients (28.1%) was not
      significantly different from that in a braced group (22.4%), the authors
      concluded that bracing appears to make no difference. Based on prior experience,
      this conclusion is questioned. METHODS: Since 1991, bracing and physical therapy
      have been recommended for children with adolescent idiopathic scoliosis at a
      centre in Barcelona, Spain. The scoliosis database was searched for patients with
      adolescent idiopathic scoliosis who were at least 15 years of age at last review
      and who had adequate documentation of the Cobb angle. The prevalence of surgery
      was compared with that of published data from a centre where the practice is non
      intervention. RESULTS: From a total of 106 braced cases out of which 97 were
      followed up, six cases (5.6%) ultimately underwent spinal fusion. A worst case
      analysis, which assumes that all nine cases that were lost to follow-up had
      operations, brings the uppermost number of cases that could have undergone spinal
      fusion to 15 (14.1%). Either percentage is significant statistically when
      compared to the 28.1% reported surgeries from the centre with the policy of non
      intervention. CONCLUSIONS: If conservative management does reduce the proportion
      of children with adolescent idiopathic scoliosis that require surgery, it can be
      said to provide a real and meaningful advantage to both the patients and the
      community. It is contended that conservative methods of treatment should never be
      ruled out from scoliosis management, because they can and do offer a viable
      alternative to those patients who cannot or will not opt for surgical treatment.

PMID- 14713588
TI  - Conservative treatment for adolescent idiopathic scoliosis: can it reduce the
      incidence of surgical treatment?
AB  - Since 1986, the authors have been conducting conservative treatment for
      idiopathic scoliosis with the combination of brace treatment and physical
      treatment (side shift exercise and hitch exercise). A total of 328 female
      patients with adolescent idiopathic scoliosis who were at least 10 years of age
      at the first visit, with Cobb angle of 10 degrees at the minimum and followed
      until after 15 years of age or skeletal maturity were included. The average Cobb
      angle was 32.4 degrees and the average age was 13.8 years at the first visit.
      Surgery was recommended when curvature progressed to >50 degrees. Twenty of 328
      patients (6.1%) with more severe curves to begin with (mean Cobb angle at
      admission of 48.5 +/- 9.3 degrees ) progressed to 62.2 +/- 8.5 degrees and were
      treated with spinal fusion by the age of 16.0 +/- 2.6 years. The remaining 308
      patients, of comparable age at inception of treatment but with a smaller original
      mean Cobb angle (32.4 +/- 11.1 degrees ), showed no significant increase in
      magnitude of curvature (mean 33.6 +/- 11.5 degrees ) by the time of discharge
      (18.6 +/- 3.1 years). The fact that curvature magnitude was maintained at <35
      degrees means that these patients will have a good prognosis for avoiding
      dramatic progression during adulthood.

PMID- 14713589
TI  - Developmental psychological aspects of scoliosis treatment.
AB  - The diagnosis and treatment of idiopathic adolescent scoliosis can have
      significant psychological consequences for affected individuals. This article
      aims to provide an overview of the current state of empirical knowledge
      concerning the psychosocial aspects of scoliosis in adolescence. These research
      results are set against experience gained from practical work. Adolescence, as a
      sensitive phase of a young person's development, requires a special degree of
      adaptation in the event of a chronic illness. For scoliosis patients this means,
      for instance, facing up to cosmetic impairments and subjectively significant
      physical defects. Cognitively the patient must come to terms with a commitment of
      time-consuming, confining, and sometimes uncomfortable treatment for a condition
      that does not always cause physical symptoms and to achieve success which is not
      necessarily defined as an improvement in the state of health. Scoliosis is a risk
      factor for impairment of the quality of life of children and adolescents. Its
      impact is particularly marked if brace-wearing is indicated. Particular attention
      needs to be paid to aspects of brace compliance. Support for patients within the
      context of in-patient rehabilitative treatment has proved to be both necessary
      and helpful. Here, within the setting of psychological group sessions and
      individual discussions, the possibility exists for preventing psychosocial
      impairment.

PMID- 14713590
TI  - Physical exercises as a treatment for adolescent idiopathic scoliosis. A
      systematic review.
AB  - Our purpose was, through an extensive and systematic review of the literature, to
      verify the effectiveness of physical exercises in the treatment of adolescent
      idiopathic scoliosis. We performed a search of different databases (Medline,
      Cochrane Library, Embase, Cinhal), and a hand-search of the non-indexed pertinent
      literature, and found 11 papers: none of the studies was randomized, six were
      prospective, seven were controlled, and two compared their results to historical
      controls; one paper had both a prospective design and a concurrent control group.
      The methodological quality of the retrieved studies was reviewed and found to be
      very poor. With one exception, the published studies demonstrated the efficacy of
      physical exercises in reducing both the rate of progression or the magnitude of
      the Cobb angle at the end of treatment. However, being of poor quality, the
      literature failed to provide solid evidence for or against the efficacy of
      physical exercises in the treatment of adolescent idiopathic scoliosis.
      Nevertheless, considering that exercises could also be proposed on the basis that
      benefits rather than to avoid progression have been shown in the literature, and
      that the results contained in published studies here reviewed suggest an effect
      on the primary goal of preventing progression, there is a basis for discussion of
      this option with patients and their families, which in turn allows decisions to
      be made according to their preferences.

PMID- 14713591
TI  - The effect of a modified Boston brace with anti-rotatory blades on the
      progression of curves in idiopathic scoliosis: aetiologic implications.
AB  - The effect of a modified Boston brace with anti-rotatory blades on idiopathic
      scoliotic curves, mainly right thoracic with a compensatory left lumbar, was
      studied. METHOD AND MATERIAL: Twenty-eight scoliotic children divided into three
      sub-groups according to the curve type were included in the study. Cobb angle and
      rotation was measured on posteroanterior spinal radiographs taken during the
      first examination and also during the follow-up with the children in and out of
      the brace. RESULTS: Ten curves improved, 13 remained stable and 5 increased (Cobb
      angle change >5 degrees compared with the initial measurement). The brace
      treatment had more affect on the double curves, while single curves remained
      unaffected. Rotation remained unchanged in all curve types except in the lumbar
      component of double (right thoracic-left lumbar) curves. DISCUSSION: These
      findings indicate that in curves with a compensatory component (e.g. main
      thoracic with compensatory lumbar curve), a deforming rotatory force, which is
      blocked by the de-rotatory action of the blades of the above-modified Boston
      brace, is present and seems to be more active in the lumbar spine. It is
      hypothesized that this deforming rotatory force seems to be a major aetiological
      factor for double curves. In conclusion the conservative treatment using this
      brace is beneficially affecting the natural history of IS in children.

PMID- 14713652
TI  - What are patients seeking when they turn to the Internet? Qualitative content
      analysis of questions asked by visitors to an orthopaedics Web site.
AB  - BACKGROUND: More people than ever are turning to the Internet for health-related
      information, and recent studies indicate that the information patients find
      online directly affects the decisions they make about their health care. Little
      is known about the information needs or actual search behavior of people who use
      the Internet for health information. OBJECTIVE: This study analyzes what people
      search for when they use a health-education Web site offering information about
      arthritis, orthopaedics, and sports-medicine topics. Additionally, it determines
      who is performing these searches: is it patients, friends or relatives of
      patients, or neither? Finally, it examines the similarities and differences among
      questions submitted by Web site visitors from different countries. METHODS:
      Content analysis was performed on 793 free-text search queries submitted to a
      patient-education Web site owned and operated by the Department of Orthopaedics
      and Sports Medicine at the University of Washington Medical Center. The 793-query
      data set was coded into 3 schemes: (1) the purpose of the query, (2) the topic of
      the query, and (3) the relationship between the asker of the query and the
      patient. We determined the country from which each query was submitted by
      analyzing the Internet Protocol addresses associated with the queries. RESULTS:
      The 5 most frequent reasons visitors searched the Web site were to seek: (1)
      information about a condition, (2) information about treatment, (3) information
      about symptoms, (4) advice about symptoms, and (5) advice about treatment. We
      were able to determine the relationship between the person submitting the query
      and the patient in question for 178 queries. Of these, the asker was the patient
      in 140 cases, and the asker was a friend or relative of the patient in 38 cases.
      The queries were submitted from 34 nations, with most coming from the United
      States, Australia, the United Kingdom, and Canada. When comparing questions
      submitted from the United States versus those from all other countries, the 3
      most frequent types of questions were the same for both groups (and were the top
      3 question types listed above). CONCLUSIONS: These results provide the University
      of Washington Department of Orthopaedics and Sports Medicine, as well as other
      organizations that provide health-information Web sites, with data about what
      people around the world are seeking when they turn to the Internet for health
      information. If Web site managers can adapt their health-information Web sites in
      response to these findings, patients may be able to find and use Internet-based
      health information more successfully, enabling them to participate more actively
      in their health care.

PMID- 14713653
TI  - Adolescents searching for health information on the Internet: an observational
      study.
AB  - BACKGROUND: Adolescents' access to health information on the Internet is partly a
      function of their ability to search for and find answers to their health-related
      questions. Adolescents may have unique health and computer literacy needs.
      Although many surveys, interviews, and focus groups have been utilized to
      understand the information-seeking and information-retrieval behavior of
      adolescents looking for health information online, we were unable to locate
      observations of individual adolescents that have been conducted in this context.
      OBJECTIVE: This study was designed to understand how adolescents search for
      health information using the Internet and what implications this may have on
      access to health information. METHODS: A convenience sample of 12 students (age
      12-17 years) from 1 middle school and 2 high schools in southeast Michigan were
      provided with 6 health-related questions and asked to look for answers using the
      Internet. Researchers recorded 68 specific searches using software that captured
      screen images as well as synchronized audio recordings. Recordings were reviewed
      later and specific search techniques and strategies were coded. A qualitative
      review of the verbal communication was also performed. RESULTS: Out of 68
      observed searches, 47 (69%) were successful in that the adolescent found a
      correct and useful answer to the health question. The majority of sites that
      students attempted to access were retrieved directly from search engine results
      (77%) or a search engine's recommended links (10%); only a small percentage were
      directly accessed (5%) or linked from another site (7%). The majority (83%) of
      followed links from search engine results came from the first 9 results.
      Incorrect spelling (30 of 132 search terms), number of pages visited within a
      site (ranging from 1-15), and overall search strategy (eg, using a search engine
      versus directly accessing a site), were each important determinants of success.
      Qualitative analysis revealed that participants used a trial-and-error approach
      to formulate search strings, scanned pages randomly instead of systematically,
      and did not consider the source of the content when searching for health
      information. CONCLUSIONS: This study provides a useful snapshot of current
      adolescent searching patterns. The results have implications for constructing
      realistic simulations of adolescent search behavior, improving distribution and
      usefulness of Web sites with health information relevant to adolescents, and
      enhancing educators' knowledge of what specific pitfalls students are likely to
      encounter.

PMID- 14713654
TI  - Reasons for consulting a doctor on the Internet: Web survey of users of an Ask
      the Doctor service.
AB  - BACKGROUND: In 1998 the Swedish noncommercial public health service Infomedica
      opened an Ask the Doctor service on its Internet portal. At no charge, anyone
      with Internet access can use this service to ask questions about personal health
      related and disease-related matters. OBJECTIVE: To study why individuals choose
      to consult previously-unknown doctors on the Internet. METHODS: Between November
      1, 2001, and January 31, 2002 a Web survey of the 3622 Ask the Doctor service
      users, 1036 men (29%) and 2586 (71%) women, was conducted. We excluded 186
      queries from users. The results are based on quantitative and qualitative
      analysis of the answers to the question "Why did you choose to ask a question at
      Infomedica's 'Ask the Doctor' service?" RESULTS: 1223 surveys were completed
      (response rate 36 %). Of the participants in the survey 322 (26%) were male and
      901 (74%) female. As major reasons for choosing to consult previously-unknown
      doctors on the Internet participants indicated: convenience (52%), anonymity
      (36%), "doctors too busy" (21%), difficult to find time to visit a doctor (16%),
      difficulty to get an appointment (13%), feeling uncomfortable when seeing a
      doctor (9%), and not being able to afford a doctors' visit (3%). Further motives
      elicited through a qualitative analysis of free-text answers were: seeking a
      second opinion, discontent with previous doctors and a wish for a primary
      evaluation of a medical problem, asking embarrassing or sensitive questions,
      seeking information on behalf of relatives, preferring written communication, and
      (from responses by expatriates, travelers, and others) living far away from
      regular health care. CONCLUSIONS: We found that that an Internet based Ask the
      Doctor service is primarily consulted because it is convenient, but it may also
      be of value for individuals with needs that regular health care services have not
      been able to meet.

PMID- 14713655
TI  - Generic design of Web-based clinical databases.
AB  - BACKGROUND: The complexity and the rapid evolution and expansion of the domain of
      clinical information make development and maintenance of clinical databases
      difficult. Whenever new data types are introduced or existing types are modified
      in a conventional relational database system, the physical design of the database
      must be changed accordingly. For this reason, it is desirable that a clinical
      database be flexible and allow for modifications and for addition of new types of
      data without having to change the physical database schema. The ideal clinical
      database would therefore implement a highly-detailed logical database schema in a
      completely-generic physical schema that stores the wide variety of clinical data
      in a small and constant number of tables. OBJECTIVE: The objective was to review
      the medical literature regarding generic design of clinical databases. METHODS: A
      search strategy was devised for PubMed and Google to get the best match of peer
      reviewed articles and free Web resources on the subject. RESULTS: Eight peer
      reviewed articles and a Web tutorial were found. All the resources described the
      so-called Entity-Attribute-Value (EAV) design as a means of simplifying the
      physical layout of data tables in a clinical database. In Entity-Attribute-Value
      design all data can be stored in a single generic table with conceptually 3
      columns: 1 for entity (eg, patient identification), 1 for attribute (eg, name),
      and 1 for value (eg, "Jens Hansen"). To add more descriptive fields to the entity
      class, all that is necessary is to add attribute values to be stored in the
      attribute field. The main advantages of the Entity-Attribute-Value design are
      flexibility and effective entity-centered data retrieval. The main disadvantages
      are complicated front-end programming needed to display data in a conventional
      layout that the user understands and less-efficient attribute-centered queries.
      The Internet offers unique opportunities for database deployment, eliminating
      problems of user-interface deployment. Furthermore, Web forms may be generated in
      a completely-generic fashion during run time from metadata describing the
      semantic structure of clinical information stored in the database. CONCLUSIONS:
      The Entity-Attribute-Value model is useful for generic design of clinical
      databases. Depending on the specific requirements of the application, more or
      less complex metadata models may be applied.

PMID- 14713656
TI  - Improving Web searches: case study of quit-smoking Web sites for teenagers.
AB  - BACKGROUND: The Web has become an important and influential source of health
      information. With the vast number of Web sites on the Internet, users often
      resort to popular search sites when searching for information. However, little is
      known about the characteristics of Web sites returned by simple Web searches for
      information about smoking cessation for teenagers. OBJECTIVE: To determine the
      characteristics of Web sites retrieved by search engines about smoking cessation
      for teenagers and how information quality correlates with the search ranking.
      METHODS: The top 30 sites returned by 4 popular search sites in response to the
      search terms "teen quit smoking" were examined. The information relevance and
      quality characteristics of these sites were evaluated by 2 raters. Objective site
      characteristics were obtained using a page-analysis Web site. RESULTS: Only 14 of
      the 30 Web sites are of direct relevance to smoking cessation for teenagers. The
      readability of about two-thirds of the 14 sites is below an eighth-grade school
      level and they ranked significantly higher (Kendall rank correlation, tau = 
      0.39, P =.05) in search-site results than sites with readability above or equal
      to that grade level. Sites that ranked higher were significantly associated with
      the presence of e-mail address for contact (tau = -0.46, P =.01), annotated
      hyperlinks to external sites (tau = -0.39, P =.04), and the presence of meta
      description tag (tau = -0.48, P =.002). The median link density (number of
      external sites that have a link to that site) of the Web pages was 6 and the
      maximum was 735. A higher link density was significantly associated with a higher
      rank (tau = -0.58, P =.02). CONCLUSIONS: Using simple search terms on popular
      search sites to look for information on smoking cessation for teenagers resulted
      in less than half of the sites being of direct relevance. To improve search
      efficiency, users could supplement results obtained from simple Web searches with
      human-maintained Web directories and learn to refine their searches with more
      advanced search syntax.

PMID- 14713657
TI  - Conceptual framework for a new tool for evaluating the quality of diabetes
      consumer-information Web sites.
AB  - BACKGROUND: Most existing tools for measuring the quality of Internet health
      information focus almost exclusively on structural criteria or other proxies for
      quality of information, rather than evaluating information accuracy and
      comprehensiveness. OBJECTIVE: This research sought to build a conceptual
      framework that could lay the groundwork for a robust performance-measurement
      system for evaluating the quality of Internet health information. METHODS:
      Application of the quality-of-care measurement paradigm to developing a
      conceptual framework for defining and evaluating the quality of diabetes consumer
      information Web sites. RESULTS: Performance measures related to accuracy and
      comprehensiveness of information can be added to structural criteria to provide a
      more-robust approach to Web site evaluation. CONCLUSIONS: The development and
      implementation of a reliable and valid method for evaluating the quality of
      Internet health sites could provide lay people with a tool to identify useful
      content more easily and distinguish between beneficial and misleading
      information.

PMID- 14713658
TI  - Design and testing of a tool for evaluating the quality of diabetes consumer
      information Web sites.
AB  - BACKGROUND: Most existing tools for measuring the quality of Internet health
      information focus almost exclusively on structural criteria or other proxies for
      quality information rather than evaluating actual accuracy and comprehensiveness.
      OBJECTIVE: This research sought to develop a new performance-measurement tool for
      evaluating the quality of Internet health information, test the validity and
      reliability of the tool, and assess the variability in diabetes Web site quality.
      METHODS: An objective, systematic tool was developed to evaluate Internet
      diabetes information based on a quality-of-care measurement framework. The
      principal investigator developed an abstraction tool and trained an external
      reviewer on its use. The tool included 7 structural measures and 34 performance
      measures created by using evidence-based practice guidelines and experts'
      judgments of accuracy and comprehensiveness. RESULTS: Substantial variation
      existed in all categories, with overall scores following a normal distribution
      and ranging from 15% to 95% (mean was 50% and median was 51%). Lin's concordance
      correlation coefficient to assess agreement between raters produced a rho of
      0.761 (Pearson's r of 0.769), suggesting moderate to high agreement. The average
      agreement between raters for the performance measures was 0.80. CONCLUSIONS:
      Diabetes Web site quality varies widely. Alpha testing of this new tool suggests
      that it could become a reliable and valid method for evaluating the quality of
      Internet health sites. Such an instrument could help lay people distinguish
      between beneficial and misleading information.

PMID- 14713659
TI  - Searching for cancer information on the internet: analyzing natural language
      search queries.
AB  - BACKGROUND: Searching for health information is one of the most-common tasks
      performed by Internet users. Many users begin searching on popular search engines
      rather than on prominent health information sites. We know that many visitors to
      our (National Cancer Institute) Web site, cancer.gov, arrive via links in search
      engine result. OBJECTIVE: To learn more about the specific needs of our general
      public users, we wanted to understand what lay users really wanted to know about
      cancer, how they phrased their questions, and how much detail they used. METHODS:
      The National Cancer Institute partnered with AskJeeves, Inc to develop a
      methodology to capture, sample, and analyze 3 months of cancer-related queries on
      the Ask.com Web site, a prominent United States consumer search engine, which
      receives over 35 million queries per week. Using a benchmark set of 500 terms and
      word roots supplied by the National Cancer Institute, AskJeeves identified a test
      sample of cancer queries for 1 week in August 2001. From these 500 terms only 37
      appeared >or= 5 times/day over the trial test week in 17208 queries. Using these
      37 terms, 204165 instances of cancer queries were found in the Ask.com query logs
      for the actual test period of June-August 2001. Of these, 7500 individual user
      questions were randomly selected for detailed analysis and assigned to
      appropriate categories. The exact language of sample queries is presented.
      RESULTS: Considering multiples of the same questions, the sample of 7500
      individual user queries represented 76077 queries (37% of the total 3-month
      pool). Overall 78.37% of sampled Cancer queries asked about 14 specific cancer
      types. Within each cancer type, queries were sorted into appropriate
      subcategories including at least the following: General Information, Symptoms,
      Diagnosis and Testing, Treatment, Statistics, Definition, and Cause/Risk/Link.
      The most-common specific cancer types mentioned in queries were
      Digestive/Gastrointestinal/Bowel (15.0%), Breast (11.7%), Skin (11.3%), and
      Genitourinary (10.5%). Additional subcategories of queries about specific cancer
      types varied, depending on user input. Queries that were not specific to a cancer
      type were also tracked and categorized. CONCLUSIONS: Natural-language searching
      affords users the opportunity to fully express their information needs and can
      aid users naive to the content and vocabulary. The specific queries analyzed for
      this study reflect news and research studies reported during the study dates and
      would surely change with different study dates. Analyzing queries from search
      engines represents one way of knowing what kinds of content to provide to users
      of a given Web site. Users ask questions using whole sentences and keywords,
      often misspelling words. Providing the option for natural-language searching does
      not obviate the need for good information architecture, usability engineering,
      and user testing in order to optimize user experience.

PMID- 14713660
TI  - How adolescents use technology for health information: implications for health
      professionals from focus group studies.
AB  - BACKGROUND: Adolescents present many challenges in providing them effective
      preventive services and health care. Yet, they are typically the early adopters
      of new technology (eg, the Internet). This creates important opportunities for
      engaging youths via eHealth. OBJECTIVE: To describe how adolescents use
      technology for their health-information needs, identify the challenges they face,
      and highlight some emerging roles of health professionals regarding eHealth
      services for adolescents. METHODS: Using an inductive qualitative research
      design, 27 focus groups were conducted in Ontario, Canada. The 210 participants
      (55% female, 45% male; median age 16 years) were selected to reflect diversity in
      age, sex, geographic location, cultural identity, and risk. An 8-person team
      analyzed and coded the data according to major themes. RESULTS: Study
      participants most-frequently sought or distributed information related to school
      (89%), interacting with friends (85%), social concerns (85%), specific medical
      conditions (67%), body image and nutrition (63%), violence and personal safety
      (59%), and sexual health (56%). Finding personally-relevant, high-quality
      information was a pivotal challenge that has ramifications on the depth and types
      of information that adolescents can find to answer their health questions.
      Privacy in accessing information technology was a second key challenge.
      Participants reported using technologies that clustered into 4 domains along a
      continuum from highly-interactive to fixed information sources: (1) personal
      communication: telephone, cell phone, and pager; (2) social communication: e
      mail, instant messaging, chat, and bulletin boards; (3) interactive environments:
      Web sites, search engines, and computers; and (4) unidirectional sources:
      television, radio, and print. Three emerging roles for health professionals in
      eHealth include: (1) providing an interface for adolescents with technology and
      assisting them in finding pertinent information sources; (2) enhancing connection
      to youths by extending ways and times when practitioners are available; and (3)
      fostering critical appraisal skills among youths for evaluating the quality of
      health information. CONCLUSIONS: This study helps illuminate adolescent health
      information needs, their use of information technologies, and emerging roles for
      health professionals. The findings can inform the design and more-effective use
      of eHealth applications for adolescent populations.

PMID- 14713661
TI  - How do consumers search for and appraise information on medicines on the
      Internet? A qualitative study using focus groups.
AB  - BACKGROUND: Many consumers use the Internet to find information about their
      medicines. It is widely acknowledged that health information on the Internet is
      of variable quality and therefore the search and appraisal skills of consumers
      are important for selecting and assessing this information. The way consumers
      choose and evaluate information on medicines on the Internet is important because
      it has been shown that written information on medicines can influence consumer
      attitudes to and use of medicines. OBJECTIVE: To explore consumer experiences in
      searching for and appraising Internet-based information on medicines. METHODS:
      Six focus groups (N = 46 participants) were conducted in metropolitan Sydney,
      Australia from March to May 2003 with consumers who had used the Internet for
      information on medicines. Verbatim transcripts of the group discussions were
      analyzed using a grounded theory approach. RESULTS: All participants reported
      using a search engine to find information on medicines. Choice of search engine
      was determined by factors such as the workplace or educational environments, or
      suggestions by family or friends. Some participants found information solely by
      typing the medicine name (drug or brand name) into the search engine, while
      others searched using broader terms. Search skills ranged widely from more
      advanced (using quotation marks and phrases) to less-than-optimal (such as typing
      in questions and full sentences). Many participants selected information from the
      first page of search results by looking for keywords and descriptions in the
      search results, and by looking for the source of the information as apparent in
      the URL. Opinions on credible sources of information on medicines varied with
      some participants regarding information by pharmaceutical companies as the
      "official" information on a medicine, and others preferring what they considered
      to be impartial sources such as governments, organizations, and educational
      institutions. It was clear that although most participants were skeptical of
      trusting information on the Internet, they had not paid conscious attention to
      how they selected information on medicines. Despite this, it was evident that
      participants viewed the Internet as an important source for information on
      medicines. CONCLUSIONS: The results showed that there was a range of search and
      appraisal skills among participants, with many reporting a limited awareness of
      how they found and evaluated Internet-based information on medicines. Poor
      interpretation of written information on medicines has been shown to lead to
      anxiety and poor compliance to therapy. This issue is more important for Internet
      based information since it is not subject to quality control and standardization
      as is written information on medicines. Therefore, there is a need for promoting
      consumer search and appraisal skills when using this information. Educating
      consumers in how to find and interpret Internet-based information on medicines
      may help them use their medicines in a safer and more-effective way.

PMID- 14713662
TI  - The development of coordination.
AB  - My concern in this paper is to provide a framework for analyzing the development
      of coordinated action systems. By emphasizing the general theme of pattern
      formation in coordinated action, attention is drawn to dual problems of
      establishing separable dimensions of action that are in turn combined into higher
      order configurations. During development processes of differentiation and
      integration are combined to make coordinated action possible. The rules by which
      this is accomplished, however, are still poorly understood. The perspective
      offered here is that to understand the development of coordinated action it is
      valuable to seek relative degrees of continuity-discontinuity and change
      stability from several complementary perspectives. This avoids unnecessarily
      simple "unit" concepts of coordinated action, and thereby provides the
      flexibility necessary to clarify underlying developmental pathways.

PMID- 14713663
TI  - Neuromotor synergies as a basis for coordinated intentional action.
AB  - Although neurally based units of action (neuromotor synergies) have often been
      proposed as a possible basis for coordinated intentional as well as automatic
      actions, the idea has rarely been translated into sets of testable hypotheses.
      This essay examines four issues which should facilitate the development of such
      hypotheses: (a) definitions of neuromotor synergies, (b) criteria for recognizing
      and comparing synergies in automatic and intentional actions, (c) problems in
      representing systems of synergies, and (d) models for generating intentional
      actions from sets of neuromotor synergies. Limitations of, and support for the
      neuromotor synergy hypothesis are discussed, both in general and for the specific
      cases of postural synergies and cervico-spinal reflexes. Although current data do
      not provide conclusive support for or against the neuromotor synergy hypothesis,
      the problem can be formulated in ways open to experimental investigation.

PMID- 14713664
TI  - Parallel computations for controlling an arm.
AB  - In order to control a reaching movement of the arm and body, several different
      computational problems must be solved. Some parallel methods that could be
      implemented in networks of neuron-like processors are described. Each method
      solves a different part of the overall task. First, a method is described for
      finding the torques necessary to follow a desired trajectory. The methods is more
      economical and more versatile than table look-up and requires very few sequential
      steps. Then a way of generating an internal representation of a desired
      trajectory is described. This method shows the trajectory one piece at a time by
      applying a large set of heuristic rules to a "motion blackboard" that represents
      the static and dynamic parameters of the state of the body at the current point
      in the trajectory. The computations are simplified by expressing the positions,
      orientations, and motions of parts of the body in terms of a single, non
      accelerating, world-based frame of reference, rather than in terms of the joint
      angles or an egocentric frame based on the body itself.

PMID- 14713665
TI  - Control of multimovement coordination: sensorimotor mechanisms in speech motor
      programming.
AB  - The present paper provides some hypotheses concerning the role of sensorimotor
      mechanisms in the coordination and programming of multimovement behaviors. The
      primary database is from experiments on the control of speech, a motor behavior
      that inherently requires multimovement coordination. From these data, it appears
      that coordination may be implemented by calibrated, sensorimotor actions which
      couple multiple movements for the accomplishment of common functional goals. The
      data from speech and select observations in other motor systems also reveal that
      these sensorimotor linkages are task-dependent and may underlie the intermovement
      motor equivalence that characterizes many natural motor behaviors. In this
      context, it is hypothesized also that motor learning may involve the calibration
      of these intermovement sensorimotor actions. These observations in turn provide
      some alternative perspectives on the concept of a motor program, primarily
      suggesting that individual movements and muscle contractions are not wholly
      prespecified, but shaped by sensorimotor adjustments.

PMID- 14713666
TI  - Understanding the dynamics of sexual transmission of HIV among drug-using
      populations: an integration of biological, behavioral, and environmental
      perspectives.

PMID- 14713667
TI  - The role of sexual transmission of HIV infection among injection and non
      injection drug users.
AB  - Many early studies of injecting drug users (IDUs) suggested that most HIV
      infections in this population were due to needle sharing and that sexual
      transmission was negligible or was overshadowed by parenteral routes. A few of
      the early studies suggested a potentially important role for heterosexual
      transmission, but these tended to be limited to cross-sectional data or had only
      a few years of prospective follow-up. Studies of sexual risk factors for HIV
      infection among non-injecting drug users (NIDUs) are similarly sparse. Recently,
      investigators prospectively examined both drug-related and sexual risk factors
      for HIV seroconversion among male and female IDUs with an adequate number of
      person-years to identify statistically significant associations. Other studies
      among never and former IDUs have identified associations suggesting that sexual
      transmission accounts for a substantial number of HIV seroconversions in these
      populations. Herein, highlights are discussed from recent investigations among
      IDUs in Baltimore, Maryland, and corroborating findings from the literature.
      Results from a 10-year prospective analysis of the ALIVE study and an analysis of
      the REACH studies spanning a 7-year period indicate that sexual risk factors for
      HIV infection are important in both female and male IDUs. These findings
      underscore the need for HIV interventions among drug users that incorporate
      sexual risk reduction. Based on the existing literature, a narrow focus on
      injection-related risks is an ineffective prevention strategy. Interventions that
      target specific subgroups of high-risk IDUs, such as men who have sex with men
      and inject drugs (MSM-IDUs), sex worker-IDUs and HIV-infected IDUs, deserve
      special attention.

PMID- 14713668
TI  - Transmission of STIs/HIV at the partnership level: beyond individual-level
      analyses.
AB  - Mathematical modeling of transmission dynamics of sexually transmitted infections
      (STIs) and HIV has considerably advanced HIV research by highlighting the
      importance of certain types of partnerships in epidemic spread. Notably,
      concurrent partnerships, defined as a sexual partnership in which one or more of
      the partnership members have other sexual partners while continuing sexual
      activity with the original partner, have been shown to play a fundamental role in
      potentiating the spread of STIs and HIV. Risk behaviors such as concurrency and
      sex without condoms as well as STI/HIV prevalence vary with physical, social, and
      emotional factors within partnerships. The efficiency of STI/HIV transmission
      appears to vary across types of concurrent partnerships according to the
      differing dynamics within them. Previous research on partnership dynamics has
      improved our understanding of the multidimensional aspects of sexual partnering,
      but little is understood of how these aspects of sexual partnering interact and
      increase risks for HIV, nor how types of partnerships, partnership dynamics, and
      concurrency work together to affect both the behavior of condom use and the
      biological transmission of disease. In this article, we discuss the need to
      extend our understanding of concurrency to include partnerships among men who
      have sex with men (MSM) and to differentiate between types of partnerships and to
      develop interventions to modify risk within partnerships. We also introduce a
      conceptual framework that reflects how individual and partner characteristics
      influence partnership dynamics that in turn influence risk behaviors, such as
      concurrency and not using condoms, and associated risks for STIs and HIV.

PMID- 14713669
TI  - The social course of drug injection and sexual activity among YMSM and other high
      risk youth: an agenda for future research.
AB  - The cumulative epidemiologic literature indicates that many injecting drug users
      (IDUs) initiate injection as a mode of drug administration during late
      adolescence or early adulthood. Recent studies have shown that IDUs are often
      exposed to viral infections relatively early in the course of injection,
      highlighting the importance of understanding this initiation process for both
      epidemiology and prevention. Epidemiologic evidence similarly suggests that at
      least some youth populations, most notably young men who have sex with men
      (YMSM), are at substantial risk for exposure to HIV and other sexually
      transmitted diseases (STDs) from early sexual activity. Despite the importance of
      this issue for both epidemiology and prevention, however, surprisingly little
      information is available on the social course of injection initiation, including
      the individual, social, or ecological factors that might mitigate or exacerbate
      transmission risks within the critical phase of early injection drug use.
      Similarly, we know little about the ways that YMSM and other high-risk youth
      understand risk, the kinds of exchanges and relationships in which they
      participate in the context of initiating sexual activity, or how drug use is
      operant in these exchanges and early sexual experiences. In this article, we
      explore key dimensions of the early initiation of injection and sexual risk, and
      discuss how a social network approach might be instrumental in understanding the
      social course of drug injection and sexual activities among youth and young adult
      populations.

PMID- 14713670
TI  - The next generation of HIV prevention for adolescent females in the United
      States: linking behavioral and epidemiologic sciences to reduce incidence of HIV.
AB  - Given the increasing numbers of new HIV infections among adolescent females and
      limitations of the current generation of HIV interventions, a new generation of
      interventions is needed to prevent HIV and other infections in this population.
      Interventions available today are limited by their focus on single behaviors that
      have little epidemiologic significance, such as condom use, and their failure to
      be tested among the highest risk females. Recent advances in epidemiologic
      sciences suggest that the next generation of interventions should focus on
      parenting and parenting skills, sexual risk networks in which drug use and other
      high-risk behaviors are prevalent, and neighborhoods where these networks exist.
      Future research should include formative and observational studies to inform new
      intervention trials that reach the highest risk female youth.

PMID- 14713671
TI  - Contextual determinants of drug use risk behavior: a theoretic framework.
AB  - Over the past two decades, public health research has emphasized the role of
      individual risk behaviors, primarily injection and sexual risk behaviors, in the
      spread of HIV infection. Much less emphasis has been given to understanding the
      determinants of these risk behaviors. Although individual characteristics are
      partly responsible for risky injection and sexual behaviors, they do not explain
      all the interpersonal variability in risk behavior. Contextual factors associated
      with HIV risk behavior may include structural factors (e.g., availability of
      services), social norms and attitudes (e.g., social trust), disadvantage (e.g.,
      neighborhood socioeconomic status), and features of the physical environment
      (e.g., housing quality). This article presents a conceptual framework that
      incorporates some of the key contextual domains that may affect drug use
      behavior. It also presents data from a study of street-recruited drug users as an
      example of the relations between social contextual factors and frequency of
      injecting drug use, and discusses some methodological challenges in the study of
      contextual determinants of drug use behavior.

PMID- 14713672
TI  - HIV prevention among injection drug users: the need for integrated models.
AB  - Opportunistic infections (OIs) were first recognized among injection drug users
      (IDUs) in New York City in 1981. By the mid-1980s, OIs had become associated with
      HIV infection, and attention began to focus on efforts to prevent HIV
      transmission among IDUs. Since then, a range of prevention strategies has been
      implemented and evaluated in an attempt to reduce the spread of HIV infection
      among drug users. These prevention strategies include (1) HIV testing and
      counseling and educational and behavioral interventions delivered through
      community outreach; (2) condom, bleach, and needle distribution and syringe
      access and exchange programs; (3) substance abuse treatment; and, more recently,
      (4) prevention interventions targeting HIV-positive IDUs. Data from evaluations
      of these strategies over the past 20 years have provided substantial evidence of
      effectiveness and have helped to inform network-based and structural
      interventions. Despite the cumulative empirical evidence, however, research
      findings have yet to be widely disseminated, adopted, and implemented in a
      sustained and integrated fashion. The reasons for this are unclear, but point to
      a need for improved communications with program developers and community planners
      to facilitate the implementation and evaluation of integrated intervention
      strategies, and for collaborative research to help understand policy, legal,
      economic, and local barriers to implementation.

PMID- 14713673
TI  - Feminization of the HIV epidemic in the United States: major research findings
      and future research needs.
AB  - This article describes several HIV prevention interventions that have
      demonstrated efficacy in reducing women's risk of HIV and identifies key research
      questions to be addressed in the area of HIV prevention for women. The article is
      organized in a question-and-answer format for clarity of presentation. This
      format is particularly useful in the latter half, which focuses on specific
      questions that have emerged from past and ongoing research among women. Some of
      these research questions include the following: (a) How can researchers develop
      effective strategies that can prevent women from relapsing to risky sexual
      practices? (b) What are effective HIV prevention approaches for Latina women? (c)
      How can interventions be tailored to the needs of women living with HIV? (d) How
      can we improve the efficacy and cost effectiveness of comprehensive HIV
      prevention strategies for reducing HIV and other blood-borne and sexually
      transmitted infections among women?

PMID- 14713674
TI  - Sexual risk reduction among HIV-positive drug-using men who have sex with men.
AB  - According to the US Centers for Disease Control, the majority of new HIV
      infections are the direct result of unprotected sexual relations between
      serodiscordant individuals. Thus, the development of behavioral interventions to
      increase the safer sex practices of HIV-positive individuals has the potential to
      reduce the number of new infections. Currently, less than 1% of the total US
      population is infected with HIV. Targeting behavioral interventions to this
      smaller group of HIV-positive individuals has the potential for making cost
      effective reductions in the number of new infections. Despite reports that some
      HIV-positive individuals continue to engage in high-risk behaviors, interventions
      designed to prevent secondary transmission of HIV are rare. In this era of highly
      active antiretroviral therapy (HAART), interventions for HIV-positive individuals
      are more critical than ever to address the unique challenges and issues they face
      regarding disclosure and partner notification, use of HAART and sexual risk
      behavior, and HIV-related stigma. Although a growing number of reports document
      the efficacy of sexual risk reduction interventions for HIV-positive individuals,
      to date none of these studies have focused on drug-using populations. This
      article focuses on sexual risk reduction interventions for HIV-positive men who
      have sex with men (MSM), the largest group of HIV-positive individuals in the
      United States. It reviews factors associated with high-risk behaviors and
      discusses some findings from research with HIV-positive methamphetamine users,
      including (1) data from a small qualitative study and its implications for the
      development of new interventions, and (2) baseline data from an ongoing large
      scale study of the efficacy of a theory-based sexual risk reduction intervention
      for HIV-positive methamphetamine-using MSM. The article concludes with a
      discussion of future research issues, including, for example: Can sexual risks be
      reduced in the context of active drug use? Are different patterns of drug use, or
      specific drugs, associated with increased risk behavior? How do gender, race, and
      culture relate to the efficacy of specific interventions?

PMID- 14713676
TI  - HIV prevention among drug users: an international perspective from Thailand.
AB  - All too often in reviews of HIV prevention needs, the role of drugs is summarily
      dismissed, especially in contexts where the heterosexual epidemic is the primary
      mode of transmission. Substance use and abuse, particularly injection drug use,
      play a paramount role in maintaining the heterosexual spread of HIV, as well as
      in maintaining epidemics where heterosexual spread of the infection has come
      under control due to prolonged and concerted HIV prevention activities. This
      article presents several themes to place in the developing country context what
      we have learned about substance use-related HIV prevention and the special
      problems of HIV interventions. First, the article briefly examines the
      international production and trade routes of opium and heroin and their role in
      the HIV epidemic, as well as the importance of substance abuse in heterosexual
      epidemics. Second, it presents a case study of HIV control that has been
      internationally acclaimed as one of the few successes in achieving a meaningful
      reduction in heterosexually transmitted HIV--Thailand. The Thai response to the
      injection drug use HIV epidemic, however, has been muted, and its impact on
      future epidemic dynamics is evaluated. The article concludes with a discussion of
      existing research gaps concerning the role of drug use in HIV epidemics in the
      developing world, with Thailand as an example.

PMID- 14713675
TI  - The dynamics of substance use and sex networks in HIV transmission.
AB  - This article (1) reviews the research to identify mechanisms that may underlie
      HIV heterosexual transmission in developed and developing countries, (2) examines
      linkages between sex and substance use HIV transmission risks, and (3) describes
      sex network measurement issues relevant to developing HIV preventive
      interventions. The research contributions of developed countries to understanding
      sexually transmitted HIV have long recognized the influence of substance use and
      sex networks. Research in developing countries has contributed significantly to
      the environmental and biological understanding of HIV sexual transmission
      dynamics. Although much of the research in developing countries has recruited
      participants from venues where alcohol or other substance use is pervasive (e.g.,
      truck stops), few studies have explicitly examined the relationship between HIV
      sex risk and substance use in these contexts. Finally, sex network
      characteristics and structural features, which have been found to play
      identifiable roles in the spread of HIV, are measurable at the individual level
      and can contribute substantively to the development and the evaluation of HIV
      preventive interventions implemented at the network or community level.

PMID- 14713677
TI  - On cultural competence and scientific rigor in transgender treatment.

PMID- 14713679
TI  - The public in public health ethics: the Public Health Society responds.

PMID- 14713681
TI  - What level of lead in blood is toxic for a child?

PMID- 14713682
TI  - Health effects of blood lead levels lower than 10 mg/dl in children.

PMID- 14713684
TI  - To think of peace in a time of war.

PMID- 14713685
TI  - Essential tensions in the journal.

PMID- 14713686
TI  - Addressing the health care needs of American Indians and Alaska Natives.

PMID- 14713687
TI  - Family planning in the balance.
AB  - Family planning has long been acknowledged as an effective public health
      intervention. In recent years, however, family planning has come under increased
      scrutiny from conservative politicians and constituents. National US policies
      instituted since 2001 are resulting in cutbacks in family planning programs
      worldwide. In the long run, these conservative initiatives may set back several
      decades of progress in reproductive health and reproductive rights. In promoting
      an ideologically driven approach to sexual and reproductive health, the recent
      policy developments threaten to subvert ethical standards of medical care and the
      principle of evidence-based policy.

PMID- 14713688
TI  - Reducing the public health burden from elevated blood pressure levels in the
      United States by lowering intake of dietary sodium.
AB  - Elevated blood pressure levels are a major cause of heart disease and stroke.
      Healthy People 2010 established objectives to reduce mortality from these
      diseases by 20% and to reduce the major causal factors associated with these
      elevated levels, such as excess sodium intake. The American public consumes far
      more sodium than is needed, most of which is added by food manufacturers and
      restaurants. In November 2002, the American Public Health Association adopted a
      policy resolution calling for a 50% reduction in sodium in the nation's food
      supply over the next 10 years. Such a reduction would greatly enhance the chances
      of attaining the Healthy People 2010 objectives and would save at least 150 000
      lives annually. This issue warrants public health intervention.

PMID- 14713689
TI  - Social science and health research: growth at the National Institutes of Health.
AB  - Programs within the National Institutes of Health (NIH) have recently taken steps
      to enhance social science contributions to health research. A June 2000
      conference convened by the NIH Office of Behavioral and Social Sciences Research
      highlighted the role of the social sciences in health research and developed an
      agenda for advancing such research. The conference and agenda underscored the
      importance of research on basic social scientific concepts and constructs, basic
      social science research on the etiology of health and illness, and the
      application of basic social science constructs in health services, treatment, and
      prevention research. Recent activities at NIH suggest a growing commitment to
      social science research and its integration into interdisciplinary multilevel
      studies of health.

PMID- 14713690
TI  - Using peer recruitment and OraSure to increase HIV testing.
AB  - We describe a community-based pilot study to boost HIV testing in a minority
      community through social network recruitment and a noninvasive HIV testing
      methodology. Over an 11-month period, the number of test takers at the
      intervention site increased by 71.7%, and the proportions of test takers with
      risk factors similar to those of peer recruiters (heterosexual sex and multiple
      partners) increased by 24.2% and 19.5%, respectively. At a comparison site,
      testing remained stable, while the proportion of test takers reporting
      heterosexual sex and multiple partners decreased by 42.5% and 21.8%,
      respectively. The use of a social network recruitment strategy in combination
      with an oral HIV test shows promise in increasing testing and in targeting
      populations.

PMID- 14713691
TI  - The Women's International League for Peace and Freedom. 1953.

PMID- 14713692
TI  - Peace and feminism.

PMID- 14713693
TI  - Dispelling the specter of nuclear holocaust.

PMID- 14713695
TI  - Medicaid eligibility of former Supplemental Security Income recipients with drug
      abuse or alcoholism disability.

PMID- 14713694
TI  - If suicide is a public health problem, what are we doing to prevent it?
AB  - Although not a disease, suicide is a tragic endpoint of complex etiology and a
      leading cause of death worldwide. Just as preventing heart disease once meant
      that specialists treated myocardial infarctions in emergency care settings, in
      the past decade, suicide prevention has been viewed as the responsibility of
      mental health professionals within clinical settings. By contrast, over the past
      50 years, population-based risk reduction approaches have been used with varying
      levels of effectiveness to prevent morbidity and mortality associated with heart
      disease. We examined whether the current urgency to develop effective
      interventions for suicide prevention can benefit from an understanding of the
      evolution of population-based strategies to prevent heart disease.

PMID- 14713696
TI  - Blood lead levels in Egyptian children: influence of social and environmental
      factors.

PMID- 14713697
TI  - Evaluation of healing by gentle touch for the treatment of musculoskeletal
      disorders.

PMID- 14713698
TI  - Health service access, use, and insurance coverage among American Indians/Alaska
      Natives and Whites: what role does the Indian Health Service play?
AB  - OBJECTIVES: We compared access and utilization of health services among American
      Indians/Alaska Natives (AIANs) with that among non-Hispanic Whites. METHODS: We
      used data from the 1997 and 1999 National Survey of America's Families to
      estimate odds ratios for several measures of access and utilization and the
      effects of Indian Health Service (IHS) coverage. RESULTS: AIANs had less
      insurance coverage and worse access and utilization than Whites. Over half of low
      income uninsured AIANs did not have access to the IHS. However, among the low
      income population, AIANs with only IHS access fared better than uninsured AIANs
      and as well as insured Whites for key measures but received less preventive care.
      CONCLUSIONS: The IHS partially offsets lack of insurance for some uninsured
      AIANs, but important needs were potentially unmet.

PMID- 14713699
TI  - Measuring the quality of diabetes care for older american indians and alaska
      natives.
AB  - OBJECTIVES: This study evaluated the quality of diabetes care for older American
      Indians and Alaska Natives. METHODS: We analyzed the Indian Health Service
      Diabetes Care and Outcomes Audit to determine whether completion of indicators of
      diabetes care differed as a function of age and whether additional patient and
      program factors were also associated with completion of the majority of the
      indicators. RESULTS: Completion rates varied by age group, with significantly
      lower rates seen among the youngest and oldest. Patient diabetes education and
      duration of diabetes were most strongly associated with the completion of the
      majority of these indicators. CONCLUSIONS: Further studies are needed to
      determine effective interventions, including diabetes education, to improve the
      quality of diabetes care in the youngest and oldest age groups.

PMID- 14713700
TI  - Relationship between continuity of care and diabetes control: evidence from the
      Third National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: We examined the relationship between continuity of care and diabetes
      control. METHODS: We analyzed data on 1400 adults with diabetes who took part in
      the Third National Health and Nutrition Examination Survey. We examined the
      relationship of continuity of care with glycemic, blood pressure, and lipid
      control. RESULTS: Continuity of care was associated with both acceptable and
      optimal levels of glycemic control. Continuity was not associated with blood
      pressure or lipid control. There was no difference between having a usual site
      but no usual provider and having a usual provider in any of the investigated
      outcomes. CONCLUSIONS: Continuity of care is associated with better glycemic
      control among people with diabetes. Our results do not support a benefit of
      having a usual provider above having a usual site of care.

PMID- 14713701
TI  - Prevalence and correlates of mental disorders among Native American women in
      primary care.
AB  - OBJECTIVES: We examined the lifetime and the past-year prevalence and correlates
      of common mental disorders among American Indian and Alaska Native women who
      presented for primary care. METHODS: We screened 489 consecutively presenting
      female primary care patients aged 18 through 45 years with the General Health
      Questionnaire, 12-item version. A subsample (n = 234) completed the Composite
      International Diagnostic Interview. We examined associations between psychiatric
      disorders and sociodemographic variables, boarding school attendance, and
      psychopathology in the family of origin. RESULTS: The study participants had high
      rates of alcohol use disorders, anxiety disorders, and anxiety/depression
      comorbidity compared with other samples of non-American Indian/Alaska Native
      women in primary care settings. CONCLUSIONS: There is a need for culturally
      appropriate mental health treatments and preventive services.

PMID- 14713702
TI  - Ethnicity/race, paranoia, and hospitalization for mental health problems among
      men.
AB  - OBJECTIVES: I tested the hypothesis that Black men with high levels of distrust
      (i.e., mild paranoia) are at greater risk of hospitalization for mental health
      problems than their White counterparts. METHODS: Secondary analysis was conducted
      of data from a subsample of 180 men in an epidemiological study. Mental health
      hospitalization was the outcome and ethnicity/race, mild paranoia, and their
      interaction were main predictors in a logistic regression analysis. The
      ethnicity/race by mild paranoia interaction tested the study hypothesis. RESULTS:
      The ethnicity/race by mild paranoia interaction was statistically significant.
      Contrary to the hypothesis, Black men with mild paranoia were less likely to be
      hospitalized. CONCLUSIONS: Black men's lack of trust regarding the mental health
      system may cause them not to seek services. Factors critical to increasing their
      trust are acknowledgment of racial biases in the mental health system and sincere
      efforts to eliminate racial disparities in mental health treatment.

PMID- 14713703
TI  - Unemployment and mental health: understanding the interactions among gender,
      family roles, and social class.
AB  - OBJECTIVES: We examined gender differences in the effects of unemployment on
      mental health and assessed whether such effects are associated with interactions
      among gender, family roles, and social class. METHODS: Our analysis included 3881
      employed and 638 unemployed workers, aged 25 to 64 years, interviewed in the 1994
      Catalonian Health Survey. RESULTS: Unemployment had more of an effect on the
      mental health of men (age-adjusted odds ratio [OR] = 2.98; 95% confidence
      interval [CI] = 2.30, 3.87) than on that of women (age-adjusted OR = 1.51; 95% CI
      = 1.11, 2.06). Gender differences in effects were related to family
      responsibilities and social class. CONCLUSIONS: Understanding the effects of
      unemployment on mental health requires consideration of the interactions among
      gender, family responsibilities, and social class.

PMID- 14713704
TI  - Suicide and friendships among American adolescents.
AB  - OBJECTIVES: We investigated the relationship between friendships and suicidality
      among male and female adolescents. METHODS: We analyzed friendship data on 13,465
      adolescents from the National Longitudinal Survey of Adolescent Health to explore
      the relationship between friendship and suicidal ideation and suicide attempts.
      We controlled for known factors associated with suicidality. RESULTS: Having had
      a friend who committed suicide increased the likelihood of suicidal ideation and
      attempts for both boys and girls. Socially isolated females were more likely to
      have suicidal thoughts, as were females whose friends were not friends with each
      other. Among adolescents thinking about suicide, suicide attempts appear largely
      stochastic, with few consistent risk factors between boys and girls. CONCLUSIONS:
      The friendship environment affects suicidality for both boys and girls. Female
      adolescents' suicidal thoughts are significantly increased by social isolation
      and friendship patterns in which friends were not friends with each other.

PMID- 14713705
TI  - Substance use among adults 35 years of age: prevalence, adulthood predictors, and
      impact of adolescent substance use.
AB  - OBJECTIVES: We examined the prevalence of substance use among American adults
      aged 35 years, and we considered adulthood predictors and the impact of
      adolescent substance use. METHODS: National panel data were drawn from the
      Monitoring the Future study. Logistic regressions were conducted to assess the
      impact of demographics, life experiences, and adolescent substance use on
      smoking, heavy drinking, prescription drug misuse, marijuana use, and cocaine use
      at 35 years of age. RESULTS: Factors related to increased likelihood of substance
      use include high school use, unemployment, and noncustodial parenthood. Lower use
      was associated with being female, a college graduate, a professional, married, or
      a custodial parent. CONCLUSIONS: Among those aged 35 years, substance use was
      still rather prevalent and was a function of adulthood roles, experiences, and
      previous use.

PMID- 14713706
TI  - Are rates of psychiatric disorders in the homeless population changing?
AB  - OBJECTIVES: We examined the prevalence of psychiatric illness among 3 homeless
      populations in St. Louis, Mo, in approximately 1980, 1990, and 2000. The 3
      studies were conducted with the same systemic research methodology. METHODS: We
      compared selected demographics and lifetime substance abuse and dependence and
      other mental illness among the 3 populations. RESULTS: Among the homeless
      populations we studied, the prevalence of mood and substance use disorders
      dramatically increased, and the number of minorities within these populations has
      increased. CONCLUSIONS: The prevalence of psychiatric illness, including
      substance abuse and dependence, is not static in the homeless population. Service
      systems need to be aware of potential prevalence changes and the impact of these
      changes on service needs.

PMID- 14713707
TI  - Risk and protective factors for adult and child hunger among low-income housed
      and homeless female-headed families.
AB  - OBJECTIVES: We sought to identify factors associated with adult or child hunger.
      METHODS: Low-income housed and homeless mothers were interviewed about
      socioeconomic, psychosocial, health, and food sufficiency information.
      Multinomial logistic regression produced models predicting adult or child hunger.
      RESULTS: Predictors of adult hunger included mothers' childhood sexual
      molestation and current parenting difficulties, or "hassles." Risk factors for
      child hunger included mothers' childhood sexual molestation, housing subsidies,
      brief local residence, having more or older children, and substandard housing.
      CONCLUSIONS: This study found that the odds of hunger, although affected by
      resource constraints in low-income female-headed families, were also worsened by
      mothers' poor physical and mental health. Eliminating hunger thus may require
      broader interventions than food programs.

PMID- 14713708
TI  - Comparison of health status indicators in chicago: are Black-White disparities
      worsening?
AB  - OBJECTIVES: This study examined Chicago residents' progress toward the Healthy
      People 2000 goal of reducing racial disparities in health and compared the
      results with a recent analysis of US data. METHODS: Non-Hispanic Black-to-non
      Hispanic White rate ratios were computed for 14 health status indicators for 1990
      and for 1998. RESULTS: Nationally and in Chicago, indicators for both Blacks and
      Whites improved between 1990 and 1998; however, Whites consistently fared better.
      Nationally, gaps narrowed on 10 indicators; for Chicago, they widened on 10
      indicators. CONCLUSIONS: Nationally, there is apparent progress in reducing Black
      White disparities; this is not true for Chicago. Whether failure to reduce racial
      disparities is unique to Chicago or is common to other urban centers remains an
      open question with important implications.

PMID- 14713709
TI  - Effectiveness of individually tailored calendars in promoting childhood
      immunization in urban public health centers.
AB  - OBJECTIVES: We examined the effectiveness of tailored calendars in increasing
      childhood immunization rates. METHODS: Parents of babies aged birth to 1 year (n
      = 321) received individually tailored calendars promoting immunization from 2
      urban public health centers. For each baby, an age- and sex-matched control was
      selected from the same center. Immunization status was tracked through age 24
      months. RESULTS: A higher proportion of intervention than of control babies were
      up to date at the end of a 9-month enrollment period (82% vs 65%, P <.001) and at
      age 24 months (66% vs 47%, P <.001). The younger the baby's age at enrollment in
      the program, the greater was the intervention effect. CONCLUSIONS: Tailored
      immunization calendars can help increase child immunization rates.

PMID- 14713710
TI  - Racial/ethnic differences in cigarette smoking initiation and progression to
      daily smoking: a multilevel analysis.
AB  - OBJECTIVES: We sought to identify individual and contextual predictors of
      adolescent smoking initiation and progression to daily smoking by race/ethnicity.
      METHODS: We used data from the National Longitudinal Study of Adolescent Health
      to estimate the effects of individual (adolescent, family, peer) and contextual
      (school and state) factors on smoking onset among nonsmokers (n = 5374) and
      progression to daily smoking among smokers (n = 4474) with multilevel regression
      models. RESULTS: Individual factors were more important predictors of smoking
      behaviors than were contextual factors. Predictors of smoking behaviors were
      mostly common across racial/ethnic groups. CONCLUSIONS: The few identified
      racial/ethnic differences in predictors of smoking behavior suggest that
      universal prevention and intervention efforts could reach most adolescents
      regardless of race/ethnicity. With 2 exceptions, important contextual factors
      remain to be identified.

PMID- 14713711
TI  - Maternal smoking in pregnancy, fetal development, and childhood asthma.
AB  - OBJECTIVES: We examined the relationships among maternal smoking in pregnancy,
      fetal development, and the risk of asthma in childhood. METHODS: We conducted a
      population-based cohort study, where all 58 841 singleton births were followed
      for 7 years using nationwide registries. RESULTS: Maternal smoking increased the
      risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62
      for high exposure). Low birthweight and preterm delivery increased the risk of
      asthma at the age of 7, whereas being small for gestational age did not.
      CONCLUSIONS: Maternal smoking in pregnancy increases the risk of asthma during
      the first 7 years of life, and only a small fraction of the effect seems to be
      mediated through fetal growth.

PMID- 14713712
TI  - TGF-beta: how tolerant can it be?
AB  - A balance between an adequate immune response to an antigen or pathogen and
      tolerance is a prerequisite for normal immune homeostasis and the well-being of
      the host. In this complex self-regulation, multiple mechanisms have been
      implicated as contributing to the immune tolerance network, including apoptosis,
      anergy, and active suppression. Current excitement focuses on active suppression
      and new regulatory T cell-mediated pathways of immunosuppression that are being
      unraveled. Central to several of these pathways is transforming growth factor
      beta (TGF-beta), a potent immunoregulatory cytokine that contributes to the
      function and generation of regulatory T cells.

PMID- 14713713
TI  - Antibody-induced transplantation tolerance: the role of dominant regulation.
AB  - A short-treatment with nondepleting antibodies, such as those targeting CD4 or
      CD154 (CD40 ligand), allows long-term graft survival without the need for
      continuous immunosuppression. This state of immune tolerance is maintained by
      regulatory CD4+ T cells present within both the lymphoid tissue and the tolerated
      graft. The nature of such regulatory T cells, their relationship to CD4+CD25+ T
      cells, and their mode of action have all been the subjects of much attention
      recently. Here, we review recent progress on understanding the nature,
      specificity, and mechanisms of action of T cells mediating dominant tolerance
      brought about by antibody therapy.

PMID- 14713714
TI  - Mechanisms of peripheral immune tolerance: conversion of the immune to the
      unresponsive phenotype.
AB  - Our studies on the immune response to foreign antigens are reviewed as they
      relate to the mechanisms of peripheral immune tolerance. The activation of
      suppressor T cells by distinct modes of antigen presentation is discussed.
      Through the use of mice expressing transgenic T-cell receptors specific for
      foreign antigens, we have concluded that the separable mechanisms of anergy and
      active suppression by CD25+ T cells work in concert to produce peripheral
      tolerance. In T-cell receptor Vbeta8.1 transgenic mice rendered tolerant of Mls
      1a, the absence of the cell surface marker 6C10 defines the anergic population of
      CD4+ T cells, while 6C10+ CD4+ T cells are actively suppressed by CD25+ T cells.
      Through discussion of these observations, we have developed a historical
      perspective on recent advances in the understanding of mechanisms of peripheral
      tolerance.

PMID- 14713715
TI  - Immune tolerance to myelin proteins.
AB  - Multiple sclerosis (MS) is a demyelinating disorder of the central nervous
      system. It is believed to be an autoimmune disease arising from a breakdown of
      immune tolerance in T cells specific for myelin antigens. The heterogeneity in
      clinical signs and pathology observed in MS patients suggests a complex
      pathogenesis in which the specificity of the pathogenic T cells and the tolerance
      mechanisms that are compromised vary among individual patients. In this review,
      we summarize some of the features of the diverse immune pathology observed in MS
      and the animal models used to study this disease. We then describe the current
      state of knowledge regarding the expression of the major myelin protein antigens
      believed to be targeted in MS and the mechanisms of immune tolerance that operate
      on T cells that recognize these antigens.

PMID- 14713717
TI  - CTLA-4 and tolerance: the biochemical point of view.
AB  - Potentially autoreactive T cells that escape negative selection in the thymus
      must be strictly controlled in the periphery to avoid autoimmune disease. The
      most robust regulatory process controlling autoreactivity is mediated by the CTLA
      4-B7 pathway. The critical homeostasis mediated by CTLA-4 was proven using
      monoclonal antibodies and genetically disrupted CTLA-4 knockout mice that develop
      polyclonal lymphocyte activation and proliferation leading to massively enlarged
      lymph nodes and spleen and fatal multiorgan lymphocytic infiltrates. CTLA-4
      ligation following T-cell activation downregulates cytokine production and cell
      cycle progression, however, the proximal biochemical basis for robust T-cell
      regulation remains unclear. In this review, we summarize studies supporting a
      dynamic role for CTLA-4 at the immunological synapse leading to direct
      attenuation of early cell signals. A model is proposed based on these
      observations, which proposes that CTLA-4 may, in fact, function under some
      circumstances in a ligand-independent manner.

PMID- 14713716
TI  - Cytokine shifts and tolerance in experimental autoimmune encephalomyelitis.
AB  - Cytokines play an important role in the pathogenesis of both multiple sclerosis
      and experimental autoimmune encephalomyelitis (EAE). Effective treatments for
      both diseases have been shown to alter cytokines in the central nervous system
      and in activated mononuclear cells. EAE is an animal model that mimics many
      aspects of multiple sclerosis, and has been widely used to study the mechanisms
      of disease and therapeutic approaches to multiple sclerosis. Cytokines play an
      important role in regulation of disease expression in EAE, and in tolerance to
      disease induction. In this review, we will summarize the current findings on the
      role of cytokine shifts in the induction of tolerance in EAE. In addition, we
      will discuss modulation of EAE by altered expression of members of the
      cytokineregulated Jak/STAT intracellular signaling pathway.

PMID- 14713718
TI  - T-cell anergy: from phenotype to genotype and back.
AB  - For many decades, anergy has been used as a descriptive term to describe a state
      of antigen-specific unresponsiveness. A better understanding of this phenotype
      was revealed in the 1980s using in vitro model systems. These model systems
      demonstrated that protein synthesis and mobilization of Ca2+ was required leading
      to the pursuit of a novel gene(s) that would be unique to the anergy phenotype.
      Several putative "anergy factors" have been suggested. In this review, we provide
      an overview of the anergy phenotype and proposed anergy-related genes. To date,
      no single gene has been described that would completely fulfill the criteria of
      an "anergy factor." We review work from our laboratory describing a novel gene
      that we have termed Gene Related to Anergy In Lymphocytes (GRAIL) that is
      upregulated in T cells anergized in vitro and in vivo and, following transduction
      into T cells, reiterates the anergy phenotype.

PMID- 14713719
TI  - Oral tolerance.
AB  - Autoimmune conditions caused by injurious immune responses against self-antigens
      can be ameliorated if the inappropriate responses to self-components that cause
      tissue injury can be modulated by regulatory cells or shut off via the induction
      of anergy or via deletion of pathogenic immune responses. Antigen encounter at
      the gut mucosa can lead to suppression of injurious immune responses to self
      antigen via these mechanisms. This type of immunological event is termed oral
      tolerance. In this review, we examine the mechanisms behind the induction of oral
      tolerance and provide findings from its use as a form of treatment for autoimmune
      diseases.

PMID- 14713720
TI  - The role of activation-induced cell death in the differentiation of T-helper-cell
      subsets.
AB  - Activation-induced cell death (AICD) has been demonstrated in T-cell hybridomas,
      immature thymocytes, and activated mature T cells. However, the molecular
      mechanisms of AICD and its physiological role in T-helper-cell differentiation
      remain uncertain. Recently, we have shown that Th1 and Th2 cells have distinct
      mechanisms of AICD. Our findings suggest that signaling from cytokines initiates
      the differentiation program, but that the selective action of death effectors
      determines the fate of differentiating T-helper cells, and thus, the ultimate
      balance between T-helper subpopulations. Among T cells, activation- induced
      expression of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL) is observed exclusively in Th2 clones and primary T-helper cells
      differentiated under Th2 conditions, while the expression of CD95L (Fas ligand)
      occurs mainly in Th1 cells. Furthermore, Th1 cells are more susceptible than Th2
      cells to apoptosis induced through either TRAIL or CD95L, and radiolabeled Th1
      cells can be induced into apoptosis via fratricide by both Th1 and Th2 cells,
      while Th2 cells are spared. The pan-caspase inhibitor, z-VAD, prevents AICD in
      Th1 cells, but not Th2 cells, indicating different mechanisms of AICD in each T
      helper subtype. Antibody blockade of TRAIL and CD95L significantly boosts
      interferon-gamma (IFN-gamma) production in vitro. Also, young mice with mutant
      CD95 (MRL/MpJ-lpr/lpr) have a stronger Th1 response to ovalbumin immunization
      than do controls. We conclude that apoptosis mediated by CD95L and TRAIL is
      critical in the selective removal of differentiating T helper cells.

PMID- 14713721
TI  - TRAIL, Bim, and thymic-negative selection.
AB  - Negative selection is a process whereby autoreactive lymphocytes are deleted
      through apoptosis. Negative selection is essential for self-tolerance and its
      breakdown may lead to the development of autoimmune diseases. Although the
      phenomenon of negative selection is well-recognized, its underlying molecular
      mechanisms are unclear. Recent studies using gene-knockout mice have provided new
      insights into the mechanisms of negative selection. In this review, we discuss
      the newly discovered roles of TRAIL and Bim in negative selection. Our main focus
      will be on T cells and T cell mediated autoimmune diseases.

PMID- 14713724
TI  - Impact of federal Substance Abuse Block Grants on state substance abuse spending:
      literature and data review.
AB  - BACKGROUND: The federal Substance Abuse Prevention and Treatment Block Grant
      (SAPTBG) was established by the U.S. Congress to assist the states in funding
      substance abuse treatment services. Although the SAPTBG represents about 40
      percent of public funding for treatment, how this federal assistance affects
      state treatment spending is not well understood. Published research has examined
      this topic, drawing on an approach from public finance economics. AIMS OF THE
      STUDY: Based on a review of the literature and data, this paper suggests future
      avenues of research on the impact of the SAPTBG. METHODS: The study reviews the
      relevant public finance economics literature and the data used in published work
      on the SAPTBG. DISCUSSION: Current literature examines only the effect of the
      block grant on expenditures by state substance abuse agencies. Additional
      analysis is needed to examine the impact of the SAPTBG on all sources of state
      funding and expenditures for substance abuse treatment. Ideas for additional
      research are presented at the end of this paper. IMPLICATIONS FOR HEALTH
      POLICIES: The increasing interest of the U.S. Congress in evaluating the
      effectiveness of the many federal block grant programs requires that further
      analysis of the impact of the SAPTBG be undertaken. The analysis and approach in
      the literature is also instructive for other countries where a central government
      allocates health care resources to local authorities using a grant.

PMID- 14713723
TI  - Use of antipsychotic medications in treating schizophrenia among different
      financing and delivery systems.
AB  - BACKGROUND: In 1995 in an effort to control costs, the State of Colorado
      implemented a pilot capitated payment system for individuals eligible for public
      financing of their mental health services. Contracts were with both Not-For
      Profit (NFP) firms and For-Profit (FP) firms; the remainder were in the fee-for
      service system (FFS). Pharmaceuticals were not included in the capitation rate.
      However, antipsychotic medications were included in the formularies for consumers
      who received their medical care through a Health Maintenance Organization (HMO).
      AIMS: This paper examines the use of antipsychotic medication compared to the use
      of atypical antipsychotics among consumers who are (i) enrolled in a medical HMO
      or not enrolled in a medical HMO and (ii) whose mental health services are
      reimbursed on a fee-for-service basis (FFS) or through a capitated system.
      METHODS: Data for this study were collected between 1995 and 1997 as part of the
      Colorado's Medicaid Mental Health Capitation Pilot Program. Atypical
      antipsychotics included in the study are: clozapine, risperidone, and olanzapine.
      The sample of this study consisted of 282 individuals diagnosed with
      schizophrenia. RESULTS: The utilization of antipsychotics was lower among
      consumers in HMOs. Compared to consumers in FFS areas of the state, the
      utilization of atypical antipsychotics was higher in capitated areas of the
      state. DISCUSSION: There was a strong incentive for the utilization of atypical
      antipsychotics to increase in capitated systems, unless consumers received their
      medication prescriptions through an HMO. Limitations include differences in
      observable and unobservable characteristics among the FFS, DC and MBHO areas,
      unavoidable selection bias and the small number of HMO enrollees. CONCLUSIONS:
      Capitation of mental health services provides incentives for more cost-effective
      treatments. HMO enrollment was not a crucial factor to determine access to
      atypical antipsychotic prescriptions. IMPLICATIONS FOR POLICY: These data suggest
      that capitation can affect the use of substitute services not in the capitation
      rate. Before recommending policy changes, we need to better understand whether
      the increased utilization leads to better outcomes. IMPLICATION FOR FURTHER
      RESEARCH: The next step is to determine whether the increased use of atypical
      antipsychotics leads to better outcomes for consumers.

PMID- 14713725
TI  - Community/hospital indicators in South African public sector mental health
      services.
AB  - BACKGROUND: The need to balance resources between community and hospital-based
      mental health services in the post-deinstitutionalisation era has been well
      documented. However, few indicators have been developed to monitor the
      relationship between community and hospital services, in either developed or
      developing countries. There is a particular need for such indicators in the South
      African context, with its history of inequitable services based in custodial
      institutions under apartheid, and a new policy that proposes the development of
      more equitable community-based care. Indicators are needed to measure the
      distribution of resources and the relative utilisation of community and hospital
      based services during the reform process. These indicators are potentially useful
      for assessing the implementation of policy objectives over time. AIMS OF THE
      STUDY: To develop and document community/hospital indicators in public sector
      mental health services in South Africa. METHODS: A questionnaire was distributed
      to provincial mental health coordinators requesting numbers of full-time
      equivalent (FTE) staff who provide mental health care at all service levels,
      annual patient admissions to hospitals and annual patient attendances at
      ambulatory care facilities. The information was supplemented by consultations
      with mental health coordinators in each of the 9 provinces. Population data were
      obtained from preliminary findings of the 1996 census. The community/hospital
      indicator measuring staff distribution was defined as the ratio of staff employed
      in community settings to all staff, expressed as a percentage. The
      community/hospital indicator measuring patient service utilisation was defined as
      the ratio of the annual ambulatory care attendance rate per 100,000 population to
      the sum of this rate and the annual hospital admission rate per 100,000
      population, expressed as a percentage. RESULTS: Of psychiatric public sector
      staff, 25% are located in community settings in South Africa (provincial range:
      11-70%). If hospital outpatient services are included in the definition of '
      'hospital' ', this figure is reduced to 17% (provincial range: 3-56%). In terms
      of service utilisation, 66% of patient contacts with mental health services occur
      through ambulatory care services in South Africa (provincial range: 44-93%).
      DISCUSSION: Community/hospital staff distribution indicates an overemphasis on
      centralised hospital-based care in most provinces and inadequate hospital care in
      certain provinces. Patterns of patient service utilisation indicate an over
      reliance on central hospital-based services and substantial unmet need. The
      findings draw attention to problems in information systems for mental health care
      in South Africa. IMPLICATIONS FOR HEALTH POLICIES: The community/hospital
      indicators developed for this study form a useful measure for assessing the
      implementation of mental health policy over time. For the South African context,
      the community/hospital indicators are a measure of the extent of resource
      redistribution from hospital to community services and changing patterns of
      service utilisation over time. Currently, patterns of resource distribution and
      service utilisation are inconsistent with government policy. IMPLICATIONS FOR
      FURTHER RESEARCH: Further research is needed into the development of mental
      health information systems, refining service indicators and improving
      methodologies for assessing the implementation of mental health policies in
      service delivery.

PMID- 14713726
TI  - Mental health service delivery following health system reform in Colombia.
AB  - BACKGROUND: In 1993, Colombia underwent an ambitious and comprehensive process of
      health system reform based on managed competition and structured pluralism, but
      did not include coverage for mental health services. AIMS OF THE STUDY: In this
      study, we sought to evaluate the impact of the reform on access to mental health
      services and whether there were changes in the pattern of mental health service
      delivery during the period after the reform. METHODS: Changes in national
      economic indicators and in measures of mental health and non-mental health
      service delivery for the years 1987 and 1997 were compared. Data were obtained
      from the National Administrative Department of Statistics of Colombia (DANE), the
      Department of National Planning and Ministry of the Treasury of Colombia, and
      from national official reports of mental health and non-mental health service
      delivery from the Ministry of Health of Colombia for the same years. RESULTS:
      While population-adjusted access to mental health outpatient services declined by
      -2.7% (-11.2% among women and +5.8% among men), access to general medical
      outpatient services increased dramatically by 46%. In-patient admissions showed
      smaller differences, with a 7% increase in mental health admissions, as compared
      to 22.5% increase in general medical admissions. DISCUSSION: The health reform in
      Colombia imposed competition across all health institutions with the intention of
      encouraging efficiency and financial autonomy. However, the challenge of
      institutional survival appears to have fallen heavily on mental health care
      institutions that were also expected to participate in managed competition, but
      that were at a serious disadvantage because their services were excluded from the
      compulsory standardized package of health benefits. While the Colombian health
      care reform intended to close the gap between those who had and those who did not
      have access to health services, it appears to have failed to address access to
      specialized mental health services, although it does seem to have promoted a
      change in the pattern of mental health service delivery from a reliance on costly
      inpatient care to more efficient outpatient services. CONCLUSIONS: Health reform
      in Colombia improved access to health services for the general medical services,
      but not for specialized mental health services. Although the primary goal of the
      health reform was to provide universal medical coverage, by not including mental
      health services in the standardized benefits package, inequities in the delivery
      of mental health services appear to have been perpetuated or even exacerbated.
      IMPLICATIONS FOR HEALTH CARE AND POLICY FORMULATION: If health reform in Colombia
      and elsewhere is to provide universal coverage and adequate access to
      comprehensive health care, mental health services must be added to the
      standardized package of health benefits and efforts to develop accessible and
      effective mental health treatment at the primary care level should continue.
      IMPLICATIONS FOR FUTURE RESEARCH: Mental health services research in Colombia
      should focus future studies on the differential impact of health reform on access
      to mental health services across regions, and between urban and rural areas.

PMID- 14713728
TI  - Imaging of high-risk plaque.
AB  - 'High-risk' or 'vulnerable' plaques in the coronary arteries have characteristics
      that make them more prone to disruption and subsequent thrombosis -- the
      mechanisms of most acute coronary syndromes (ACS). There are a number of imaging
      modalities that are capable of visualizing these features. This article discusses
      invasive modalities for identifying 'high-risk' plaque such as intravascular
      ultrasound, coronary angioscopy, optical coherence tomography, near-infrared
      spectroscopy and coronary thermography. It also discusses the use of noninvasive
      modalities such as computed tomography MRI and ultrasound. When these imaging
      modalities are combined with standard cardiac risk factors and more novel markers
      of systemic inflammation and thrombogenicity we can improve our ability to
      identify the 'high-risk' patient.

PMID- 14713729
TI  - Stem cells for the heart, are we there yet?
AB  - Although several repair mechanisms have been described in the human heart, all
      fall too short to prevent clinical heart disease in most acute or chronic
      pathological cardiac conditions. Moreover, despite many breakthroughs in
      cardiovascular medicine, the complications of a myocardial infarction such as
      chronic heart failure remains a serious worldwide problem. Bone marrow stem cells
      could provide for a promising strategy to restore myocardial infarctions and
      prevent postinfarct congestive heart failure, because there is growing body of
      evidence that bone marrow stem cells, such as mesenchymal stem cells, can
      generate new cardiomyocytes in animals and humans. In this review, we will
      discuss important issues on stem cell therapy for cardiac regeneration after
      myocardial infarction, which might be of paramount importance when considering
      future human trials.

PMID- 14713730
TI  - Sudden cardiac death in athletes.
AB  - Sudden cardiac death in athletes, although relatively uncommon, is a well
      recognized condition generally associated with some congenital abnormalities. It,
      however, continues to be of vast interest to the public as athletes are seen as a
      distinct group of individuals who are especially able to tolerate more intense
      physical activities than the general population. Obviously, intense activities
      predispose susceptible athletes to sudden cardiac death, hence the importance of
      pre-participation screening tests. As the cost of healthcare continues to be on
      the rise, there will be increasing difficulty justifying a nation-wide method of
      screening cost-effectively. This article is intended to describe the possible
      underlying causes of sudden cardiac death discovered thus far, as well as methods
      for detection, pre-participation guidelines, and emerging therapy.

PMID- 14713731
TI  - The 'Open-Artery Hypothesis': new clinical and pathophysiologic insights.
AB  - The open-artery hypothesis states that myocardial reperfusion, even if late for
      myocardial salvage, provides benefits and prevents adverse cardiac remodeling.
      While observational data in humans regarding the deleterious impact of a
      permanent infarct-related artery occlusion and the benefits of spontaneous
      reperfusion are quite consistent, the reports regarding late revascularization
      are inconclusive in order to prove such a hypothesis. The observational studies
      tend to have selection biases, while randomized trials to date are too small to
      be conclusive. Moreover, the pathophysiological mechanisms underlying presumed
      benefits of reperfusion are still unclear. However, although the open-artery
      hypothesis remains unproven, the current evidence suggesting benefits calls for
      additional studies. Limitations of ischemic left ventricular dilatation and
      myopathy could markedly reduce cardiovascular morbidity and mortality after acute
      myocardial infarction.

PMID- 14713732
TI  - Functional capacity impairment in patients with coronary artery disease:
      prevalence, risk factors and prognosis.
AB  - BACKGROUND: Some patients developing heart failure and functional capacity
      impairment have no history of myocardial infarction (MI), and stable angina
      pectoris is their principal clinical manifestation of coronary artery disease
      (CAD). The present study was aimed to evaluate the outcome of CAD-related
      functional capacity impairment in patients with and without a history of MI over
      a 7.7-year follow-up. METHODS: The study sample comprised 14,283 coronary
      patients aged 45-74 years, screened for participation in the Bezafibrate
      Infarction Prevention study. The presence of NYHA functional class II was defined
      as mild functional capacity impairment and the presence of NYHA functional class
      III-IV was defined as advanced functional capacity impairment. RESULTS: The
      patients were divided in two groups: (1) those with a history of MI, 10,307
      patients, who formed three subgroups: NYHA I 7,551 patients (73.3%); NYHA II
      2,176 patients (21.1%); NYHA III + IV 580 patients (5.6%), and (2) those without
      a history of MI, 3,976 patients, who also formed three subgroups: NYHA I 2,744
      patients (69.0%); NYHA 981 patients (24.7%); NYHA III + IV 251 patients (6.3%).
      Multivariate analysis identified a history of MI as a consistent predictor of
      increased all-cause and cardiac mortality for patients with NYHA I, II and III +
      IV subgroups with escalating significance for patients with advanced functional
      capacity impairment: hazard ratios of 1.55 (95% CI 1.36-1.75), 1.56 (95% CI 1.30
      1.86) and 1.72 (95% CI 1.24-2.40) for all-cause and 1.93 (95% CI 1.60-2.33), 1.73
      (95% 1.35-2.20) and 3.22 (95% CI 1.87-5.54) for cardiac mortality, respectively.
      CONCLUSIONS: The prevalence of low functional capacity is similar among coronary
      patients with and without a history of MI, but their long-term survival differs
      substantially in favor of the latter. Therefore, two different types of CAD
      related advanced functional capacity impairments (post-MI and non-post-MI) can be
      distinguished.

PMID- 14713733
TI  - Nurse staffing: a structural proxy for hospital quality?

PMID- 14713734
TI  - Nurse staffing and mortality for Medicare patients with acute myocardial
      infarction.
AB  - CONTEXT: Recent hospital reductions in registered nurses (RNs) for hospital care
      raise concerns about patient outcomes. OBJECTIVE: Assess the association of nurse
      staffing with in-hospital mortality for patients with acute myocardial infarction
      (AMI). DESIGN, SETTING, AND PATIENTS: Medical record review data from the 1994
      1995 Cooperative Cardiovascular Project were linked with American Hospital
      Association data for 118,940 fee-for-service Medicare patients hospitalized with
      AMI. Staffing levels were represented as nurse to patient ratios categorized into
      quartiles for RNs and for licensed practical nurses (LPNs). MAIN OUTCOME
      MEASURES: In-hospital mortality. RESULTS: From highest to lowest quartile of RN
      staffing, in-hospital mortality was 17.8%, 17.4%, 18.5%, and 20.1%, respectively
      (P < 0.001 for trend). However, from highest to lowest quartile of LPN staffing,
      mortality was 20.1%, 18.7%, 17.9%, and 17.2%, respectively P < 0.001). After
      adjustment for patient demographic and clinical characteristics, treatment, and
      for hospital volume, technology index, and teaching and urban status, patients
      treated in environments with higher RN staffing were less likely to die in
      hospital; odds ratios (95% confidence intervals) of quartiles 4, 3, and 2 versus
      quartile 1 were 0.91 (0.86-0.97), 0.94 (0.88-1.00), and 0.96 (0.90-1.02),
      respectively. Conversely, after adjustment, patients treated in environments with
      higher LPN staffing were more likely to die in-hospital; odds ratios (95%
      confidence intervals) of quartiles 4, 3, and 2 versus quartile 1 were 1.07 (1.00
      1.15), 1.02 (0.96-1.09), and 1.00 (0.94-1.07), respectively. CONCLUSIONS: Even
      after extensive adjustment, higher RN staffing levels were associated with lower
      mortality. Our findings suggest an important effect of nurse staffing on in
      hospital mortality.

PMID- 14713735
TI  - Feasibility and reliability of a mailed questionnaire to obtain visual analogue
      scale valuations for health states defined by the Health Utilities Index Mark 3.
AB  - To establish the generalizability (external validity) of the Health Utilities
      Index Mark 3 (HUI3) as a single-summary score generic outcome measure in numerous
      countries/subgroups (including children), repeated studies of community
      preferences should be performed in various settings. In performing multiple HUI3
      studies, a mailed questionnaire approach, if feasible and reliable, might be
      substituted for oral interviews. In the present study, we assessed the
      feasibility and reliability of a mailed questionnaire approach originally
      developed for the EQ-5D, for the purpose of collecting Visual Analogue Scale
      (VAS) valuations from parents as surrogate responders for 65 pediatric HUI3
      health states and for the state of being dead. Untransformed mean VAS scores of
      the health states and scores converted into preliminary Standard Gamble (SG)
      utilities were compared with Canadian and French multiattribute utility
      estimates. A random sample of 1920 parents of schoolchildren (aged 4 to 13)
      received a mailed questionnaire. Each parent was asked to rate 6 HUI3 health
      states on a 0 to 100 VAS. Response was 70%. Mean completion time was 20 minutes
      (SD 9). The questionnaire was rated difficult by only 9%. The current format was,
      however, inappropriate for valuing the state of being dead. Interrater
      reliability of health state valuations was.87. Spearman's rank correlations,
      Pearson-R correlations and intra class correlation coefficients (ICCs) between
      untransformed VAS valuations and Canadian/French utility estimates were > or
      =.87. However, preliminary SG-utilities showed diminished ICCs (.71 to.72). The
      data support the feasibility and reliability of mailed HUI3 valuation
      questionnaires to a considerable extent, but further methodological studies
      regarding other formats and different populations are recommended.

PMID- 14713736
TI  - Comparing alternative measures of functional limitation.
AB  - BACKGROUND: Functional limitation is a central concept in the disability process,
      but its operationalization has varied widely, making it impossible to compare
      results across studies. OBJECTIVE: Our goal is to systematically compare the
      effectiveness of alternative measures of functional limitations to predict
      disability and to provide guidelines for their standardization. DESIGN: Over 100
      alternative scales of functional limitations are compared in regression models of
      disability. The Bayesian information criterion is used to compare the performance
      of measures. SUBJECTS: The subjects were 5,764 women, aged 37 to 68, from the
      Mature and Young Women's cohorts of the National Longitudinal Surveys. MEASURES:
      Scales are constructed from 9 indicators of activity limitations: (1) grasping,
      (2) lifting/carrying up to 10 pounds, (3) lifting/carrying heavy weights, (4)
      reaching, (5) sitting, (6) stairs, (7) standing, (8) stooping, and (9) walking.
      Respondents were asked whether they could perform the activity without
      difficulty, with difficulty, or could not perform it at all. The 4 disability
      outcomes include binary and ordinal measures of work limitation, a single ADL
      measure (bathing), and total number of ADLs. RESULTS: The 3 best scales used all
      9 indicators. The top scale truncated values above 5, while the others logged the
      sum. Two scales were based on sums of binary indicators, while the third used 3
      category indicators. CONCLUSIONS: Simple scales perform better than complex
      scales that separate upper and lower body limitations or weight some limitations
      more than others. Scales that transform higher values are preferable.

PMID- 14713737
TI  - The effects of organization on medical utilization: an analysis of service line
      organization.
AB  - OBJECTIVES: To determine whether clinical service lines in primary care and
      mental health reduces inpatient and urgent care utilization. METHODS: All VHA
      medical centers were surveyed to determine whether service lines had been
      established in primary care or mental health care prior to the beginning of
      fiscal year 1997 (FY97). Facility-level data on medical utilization from Veterans
      Health Affairs (VHA) administrative databases were used for descriptive and
      multivariate regression analyses of utilization and of changes in measures
      between FY97 and FY98. Nine primary care-related and 5 mental health-related
      variables were analyzed. PRINCIPAL FINDINGS: Primary care and mental health
      service lines had been established in approximately half of all facilities.
      Service lines varied in duration and extent of restructuring. Mere presence of a
      service line had no positive and several negative effects on measured outcome
      variables. More detailed analyses showed that some types of service lines have
      statistically significant and mostly negative effects on both mental health and
      primary care-related measures. Newly implemented service lines had significantly
      less improvement in measures over time than facilities with no service line.
      CONCLUSIONS: Health care organizations are implementing innovative organizational
      structures in hopes of improving quality of care and reducing resource
      utilization. We found that service lines in primary care and mental health may
      lead to an initial period of disruption, with little evidence of a beneficial
      effect on performance for longer duration service lines.

PMID- 14713738
TI  - Quantifying income-related inequality in healthcare delivery in the United
      States.
AB  - BACKGROUND: Numerous studies have found that high-income Americans use more
      medical care than their low-income counterparts, irrespective of medical "need."
      The methods employed in these studies, however, make it difficult to evaluate
      differences in the degree of income-related inequality in utilization across
      population subgroups. In this study, we derive a summary index to quantify income
      related inequality in need-adjusted medical care expenditures and report values
      of the index for adults and children in the United States. METHODS: We used the
      summary index of income-related inequality in expenditures developed by Wagstaff
      et al. 1 The source of data for the study was the Household Component of the 1996
      1998 Medical Expenditure Panel Survey, which contains person-level data on
      medical care expenditures, demographic characteristics, household income, and a
      wide array of health status measures. We used multivariate regression analysis to
      predict need-adjusted annual medical care expenditures per person by income level
      and used the predictions to calculate the indices of inequality. Separate indices
      were calculated for all adults, working-age adults, seniors, and children ages 5
      to 17. RESULTS: For all age groups, predicted expenditures per person, adjusted
      for medical need, generally increased as income rose. The index of inequality for
      all adults was +0.087 (95% confidence interval, +0.035, +0.139); for working-age
      adults, +0.099 (+0.046, +0.152); for seniors, +0.147 (+0.059, +0.235); and for
      children, +0.067 (+0.006, +0.128). CONCLUSIONS: There exists income-related
      inequality in medical care expenditures in the United States, and it favors the
      wealthy. The inequality is highest among seniors despite Medicare, intermediate
      among working-age adults, and lowest among children.

PMID- 14713739
TI  - An evaluation of the impact of the prospective payment system on antidepressant
      use in nursing home residents.
AB  - OBJECTIVES: To determine the impact of the prospective payment system (PPS) for
      skilled nursing facilities on the pharmacologic treatment of depression. METHODS:
      We used a quasi-experimental study comparing the pharmacological treatment rates
      for depression in the pre-PPS period (1997) to the post-PPS period (2000) in 8149
      residents with documented depression living in over 500 nursing facilities in
      Ohio. Logistic regression models adjusting for clustering effects of residents
      residing in homes using generalized estimating equations provided estimates of
      the PPS effect on use of any antidepressant and the use of selective serotonin
      reuptake inhibitors (SSRIs). We evaluated the extent to which the PPS effect was
      modified by organizational characteristics, including structural characteristics,
      resource characteristics, and staff resources available in the homes. RESULTS:
      Overall, there was no difference in the likelihood of any antidepressant [odds
      ratio (OR), 1.05; 95% confidence interval (CI), 0.93 to 1.18, resident-adjusted
      model] or an SSRI being used (OR, 0.98; 95% CI, 0.86 to 1.12, resident-adjusted
      model) after the introduction of PPS compared with 1997 when this reimbursement
      system was not in place (referent group). These trends did not appear to be
      modified substantially by organizational characteristics. CONCLUSION: Although
      PPS did not appear to have influenced the treatment of depression in nursing
      homes, systems that provide checks and balances in relation to PPS are warranted.

PMID- 14713740
TI  - Relationship between processes of care and coronary bypass operative mortality
      and morbidity.
AB  - BACKGROUND: Information is limited regarding the effects of processes of care on
      cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical
      processes of care are derived from animal experiments or clinical judgment. This
      report from the VA Cooperative Study in Health Services, "Processes, Structures,
      and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process
      groups (preoperative evaluation, intraoperative care, and supervision by senior
      physicians) and a composite outcome, perioperative mortality and morbidity.
      METHODS: Data on 734 risk, process, and structure variables were collected
      prospectively on 3,988 patients who underwent coronary artery bypass grafting at
      14 VA medical centers between 1992 and 1996. Data reduction was accomplished by
      examining data completeness and variation across sites and surgeon, using
      previously published data and clinical judgment. We then applied multivariable
      logistic regression to the 39 remaining processes of care to determine which were
      related to the composite outcome after adjusting for 17 patient-related risk
      factors and controlling for intraoperative complications. RESULTS: Our first
      analysis showed several measures of operative duration, the use of inotropic
      agents, transesophageal echo, lowest systemic temperature, and
      hemoconcentration/ultrafiltration, to be powerful predictors of the composite
      outcome. Because the use of inotropic agents and operative duration may be
      related to an intermediate outcome (eg, intraoperative complications), we
      performed a second analysis omitting these processes. The use of intraoperative
      transesophageal echo and hemoconcentration/ultrafiltration remained significantly
      associated with an increased risk of an event (odds ratios 1.60 and 1.36,
      respectively). CONCLUSIONS: Our results viewed in the context of past studies
      suggest the possibility that inotropic use, TEE, and
      hemoconcentration/ultrafiltration may have adverse effects on operative outcome.
      Further evaluation of these processes of care using observational data, as well
      as randomized trials when feasible, would be of interest.

PMID- 14713741
TI  - A new method for evaluating the quality of medical interpretation.
AB  - OBJECTIVES: To develop and implement a method to evaluate the quality of medical
      interpretation in a pediatric outpatient setting and explore the patterns and
      correlates of errors and failures in translation. DESIGN, SETTING, AND PATIENTS:
      Observational study of a convenience sample of 13 Spanish-speaking families
      attending pediatric outpatient clinics at an urban teaching hospital, their
      English-speaking providers, and interpreters. Visits were audiotaped and
      transcribed. The transcripts were divided into segments consisting of continuous
      sections of dialogue in a single language, plus any translation of that dialogue,
      and segments were coded for characteristics of the translation, word count, and
      the identity of the speakers. MAIN OUTCOME MEASURES: Translation quality on an
      ordinal scale derived from a set of nominal codes. RESULTS: We found that 66.1%
      of segments in which translation should have occurred were translated with
      substantial errors or omissions or not translated at all. In 29.8% of segments,
      the interpreter engaged in speech unrelated to interpretation. Quality of
      interpretation was inversely associated with the word count per segment and,
      independently, whether the interpreter engaged in speech acts which did not
      consist of interpretation, which we call "role exchange." We give several
      examples and qualitative discussion of "role exchange" and show that it not
      necessarily associated with mistranslation but may have egregious consequences.
      CONCLUSIONS: Interpreters who lack appropriate training fail to interpret
      accurately. Engaging in speech behaviors other than interpreting is associated
      with a higher rate of errors.

PMID- 14713742
TI  - Clinical Risk Groups (CRGs): a classification system for risk-adjusted capitation
      based payment and health care management.
AB  - OBJECTIVE: To develop Clinical Risk Groups (CRGs), a claims-based classification
      system for risk adjustment that assigns each individual to a single mutually
      exclusive risk group based on historical clinical and demographic characteristics
      to predict future use of healthcare resources. STUDY DESIGN/DATA SOURCES: We
      developed CRGs through a highly iterative process of extensive clinical
      hypothesis generation followed by evaluation and verification with computerized
      claims-based databases containing inpatient and ambulatory information from 3
      sources: a 5% sample of Medicare enrollees for years 1991-1994, a privately
      insured population enrolled during the same time period, and a Medicaid
      population with 2 years of data. RESULTS: We created a system of 269
      hierarchically ranked, mutually exclusive base-risk groups (Base CRGs) based on
      the presence of chronic diseases and combinations of chronic diseases. We
      subdivided Base CRGs by levels of severity of illness to yield a total of 1075
      groups. We evaluated the predictive performance of the full CRG model with R2
      calculations and obtained values of 11.88 for a Medicare validation data set
      without adjusting predicted payments for persons who died in the prediction year,
      and 10.88 with a death adjustment. A concurrent analysis, using diagnostic
      information from the same year as expenditures, yielded an R2 of 42.75 for 1994.
      CONCLUSION: CRGs performance is comparable to other risk adjustment systems. CRGs
      have the potential to provide risk adjustment for capitated payment systems and
      management systems that support care pathways and case management.

PMID- 14713743
TI  - Continuity of medical care, health insurance, and nonmedical advice in the first
      3 years of life.
AB  - OBJECTIVES: The study seeks to evaluate whether continuity in medical care
      provides a mechanism that contributes to increased parental awareness of the
      importance of dental services, nutrition, and child development and whether
      health insurance encourages such continuity. METHODS: Data pertaining to medical
      utilization and dental, child nutrition, and child development counseling were
      extracted from the National Maternal and Infant Health Survey, 1988 and the 1991
      Longitudinal Follow-up. These data permit the investigation of whether having
      continuity in medical care for a child increases the likelihood that the child's
      parent receives advice about dental health, nutrition, and child development.
      Restricting the analyses to Caucasian and African American women and excluding
      respondents with missing information on the child's health care utilization
      yielded 7056 participants. We created a set of binomial logit models, with
      correction for clustering (due to sample design). These models jointly estimate
      the likelihood that a child was classified as having continuity of care and the
      likelihood that the child's mother received advice about the 3 areas of interest.
      RESULTS: Private fee-for-service health insurance was found to increase the
      likelihood that a child receives continuity of care. When primary care was
      provided with high continuity of care, the probability that physicians provide
      mothers with dental, nutritional, and developmental advice was increased.
      CONCLUSIONS: These results suggest that continuity of care may have important
      spillover effects beyond direct medical care by improving maternal information
      about child dental care, nutrition, and developmental issues.

PMID- 14713744
TI  - First International Conference on Chemoprevention of Prostate Cancer. Overview
      consensus statement.

PMID- 14713745
TI  - Prostate cancer chemoprevention: an overview of United States trials.
AB  - PURPOSE: We review the current status of clinical trials investigating the use of
      interventions designed to reduce the risk of prostate cancer. MATERIALS AND
      METHODS: A comprehensive review of the literature was conducted, which included
      the Ovid database and recent abstract proceedings from national meetings relevant
      to chemoprevention trials in prostate cancer. All clinical trials sponsored by
      the National Institutes of Health and National Cancer Institute in the United
      States were included. RESULTS: A total of 11 randomized controlled trials were
      found to be currently recruiting patients in the United States. These randomized
      controlled trials are designed to investigate the efficacy of a variety of agents
      ranging from dietary supplements to laboratory manufactured drugs, such as
      finasteride and cyclooxygenase-2 inhibitors, for the primary chemoprevention of
      prostate cancer. CONCLUSIONS: Chemoprevention of prostate cancer is currently
      being tested in a wide range of clinical trials. These studies have the potential
      to fundamentally alter the current approach to prostate cancer management.

PMID- 14713746
TI  - Chemotherapeutic prevention studies of prostate cancer.
AB  - PURPOSE: Despite advances in the detection and management of prostate cancer,
      this disease remains a major cause of morbidity and mortality in men. Increasing
      attention has focused on the role of chemoprevention for prostate cancer, ie the
      administration of agents that inhibit 1 or more steps in the natural history of
      prostate carcinogenesis. We review prostate cancer chemoprevention studies in
      Europe. MATERIALS AND METHODS: Published studies were identified in a search of
      MEDLINE. Information about ongoing studies was provided by author access to
      protocols. RESULTS: A variety of chemoprevention studies have focused on the role
      of dietary factors, vitamins and trace elements in prostate cancer. Some of these
      studies have been prospective, randomized and double-blinded, while others have
      used retrospective or epidemiological approaches. Large scale randomized studies
      are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the
      conversion of testosterone to the more potent androgen dihydrotestosterone.
      CONCLUSIONS: Robust evidence is lacking for the value of chemopreventive agents
      in prostate cancer. Current evidence does suggest that vitamin E and selenium may
      have a role in prostate cancer chemoprevention. Data from 2 studies, 1 examining
      the type 1 5alpha-reductase selective inhibitor finasteride and the other using
      the dual 5alpha-reductase inhibitor dutasteride, will determine the benefits of
      androgen inhibition strategies for prostate cancer chemoprevention.

PMID- 14713747
TI  - The Prostate Cancer Prevention Trial: current status.
AB  - PURPOSE: The rationale, design considerations and current status of the Prostate
      Cancer Prevention Trial (PCPT) are presented. MATERIALS AND METHODS: The design
      considerations for a prevention study involving finasteride were reviewed. Most
      notable was the end of study biopsy planned for all participants to eliminate any
      detection bias caused by the effect of finasteride on prostate specific antigen.
      RESULTS: During a 3-year period 18,882 men were randomized in the PCPT. The final
      end of study biopsy is planned for May 2004. The study was closed 15 months
      before the final anticipated participant biopsy by the independent Data and
      Safety Monitoring Committee due to a 24.8% reduction in prostate cancer with
      finasteride. CONCLUSIONS: The extraordinary accrual of PCPT of healthy men in a
      prospective study to test an intervention for prostate cancer prevention
      illustrates the potential for future studies. The positive results of the trial
      as well as many observations that have been made of the study population argue
      for increased emphasis on prevention research for highly prevalent genitourinary
      malignancies.

PMID- 14713748
TI  - Dietary fat and prostate cancer.
AB  - PURPOSE: Data from histopathological and migratory studies suggest that 1 or more
      late stage environmental promoters are involved in the development of clinical
      carcinoma of the prostate. Laboratory investigations and variously designed
      epidemiological studies in man have suggested that dietary fat may be one of
      these candidate tumor promoters but other studies have questioned this
      association. The biologically plausible associations that have been hypothesized
      include total energy consumption, altered androgen metabolism, oxidative stress,
      specific fatty acid consumption and pesticide intake. We provide a critical
      appraisal of the existing evidence for an association between dietary fat
      consumption and prostate cancer, and review the biologically plausible
      relationships. MATERIALS AND METHODS: All 33 published case-control and cohort
      studies that examined the relationship between prostate cancer and dietary fat or
      specific fatty food types were critically appraised. Eight studies suggested a
      statistically significant association, and many studies noted significant
      associations for specific types of fatty foods (eg milk or meat) and prostate
      cancer. RESULTS: In light of the inherent biases in the methodology of studying
      dietary fat intake and carcinoma of the prostate, we conclude that the evidence
      is consistent. CONCLUSIONS: Corroborative studies in humans are required to
      better define this relationship. Prospective studies of dietary intervention
      should be encouraged.

PMID- 14713749
TI  - Molecular epidemiology of androgen-metabolic loci in prostate cancer:
      predisposition and progression.
AB  - PURPOSE: We review recent molecular epidemiological data with regard to the
      association between several allelic variants of certain androgen-metabolic genes
      and the predisposition to and progression of prostate cancer. MATERIALS AND
      METHODS: We review recent data dealing with genetic variations in androgens and
      the etiology of prostate cancer. RESULTS: Recent molecular epidemiological data
      support an association between several allelic variants of certain androgen
      metabolic genes and the predisposition to and progression of prostate cancer.
      While some of the allelic variants examined are consistently shown to be
      associated with increased prostate cancer risk, most of the variants show
      significant variability in risk. CONCLUSIONS: A multidisciplinary attack on this
      problem, involving biochemistry, molecular genetics, pharmacogenetics,
      endocrinology and epidemiology, may be a useful paradigm in the analysis of
      prostate cancer and other complex human diseases. Based on the reviewed
      literature, we propose a guide on how and which single nucleotide polymorphisms
      to use in linkage and association studies of multifactorial phenotypes.

PMID- 14713750
TI  - Inflammation as a target for prostate cancer chemoprevention: pathological and
      laboratory rationale.
AB  - PURPOSE: We review the literature addressing a potential causal role for chronic
      or recurrent inflammation or infection in the development of prostate cancer.
      MATERIALS AND METHODS: A literature search was conducted using MEDLINE to
      identify articles on chronic inflammation as a risk factor for cancer,
      particularly prostate cancer. RESULTS: A causal role for chronic or recurrent
      inflammation or infection in the development of prostate cancer has yet to be
      proven. Inflammation may contribute to carcinogenesis by 1 or more of several
      potentially interrelated mechanisms, including 1) the elaboration of cytokines
      and growth factors that favor tumor cell growth, 2) induction of cyclooxygenase-2
      in macrophages and epithelial cells, and 3) generation of mutagenic reactive
      oxygen and nitrogen species. Chronic inflammation in the form of stromal and
      epithelial infiltrates of lymphocytes and histiocytes is extremely common in the
      peripheral zone of the prostate where most cancers arise. Although differences in
      histology and terminology exist for these inflammatory and atrophic lesions, as a
      group they often display evidence of epithelial proliferation. Heterogeneous
      expression of the GSTP1 gene in such lesions has been proposed as evidence for
      susceptibility to oxidative damage, thereby providing fertile ground for
      carcinogenesis. CONCLUSIONS: Although the cumulative evidence demonstrates that
      chronic inflammation may be a legitimate target for chemopreventive efforts, more
      study is needed to prove its etiological role in prostate cancer.

PMID- 14713751
TI  - Epidemiology of inflammation and prostate cancer.
AB  - PURPOSE: We provide an overview of some of the basic, clinical and
      epidemiological research that has been conducted to investigate the potential
      role of chronic inflammation in prostate carcinogenesis and to provide direction
      for future research on this hypothesis. MATERIALS AND METHODS: We reviewed the
      literature on this topic. RESULTS: Chronic inflammation has long been linked to
      cancers with an infectious etiology, such as stomach, liver and colon cancer, in
      patients with inflammatory bowel disease. Whether intraprostatic inflammation
      contributes to prostate carcinogenesis is unknown. Inflammation is frequently
      present in prostate biopsies, radical prostatectomy specimens and tissue resected
      for treatment of benign prostatic hyperplasia. Also, inflammatory infiltrates are
      often found in and around foci of atrophy that are characterized by an increased
      proliferative index. These foci, called proliferative inflammatory atrophy, may
      be precursors of early prostate cancer or may indicate an intraprostatic
      environment favorable to cancer development. Epidemiological studies have
      indirectly examined the role of chronic inflammation in prostate carcinogenesis
      through studies of pro-inflammatory and anti-inflammatory factors. When taken
      together studies of sexually transmitted infections, clinical prostatitis, and
      genetic and circulating markers of inflammation and response to infection hint at
      a link between chronic intraprostatic inflammation and prostate cancer.
      CONCLUSIONS: Additional well-designed basic, clinical and epidemiological studies
      are needed to resolve questions about the role of chronic inflammation in
      prostate carcinogenesis and to determine if intraprostatic inflammation is a
      rational target for chemoprevention.

PMID- 14713753
TI  - Genetic variations in the vitamin D receptor, androgen receptor and enzymes that
      regulate androgen metabolism.
AB  - PURPOSE: We review the current literature on genetic variations in the vitamin D
      receptor (VDR), androgen receptor (AR) and enzymes regulating androgen
      development. MATERIALS AND METHODS: A MEDLINE search was conducted to identify
      research investigating associations between polymorphisms in important regulatory
      genes that may indirectly affect cancer risk, with special regard to prostate
      cancer. RESULTS: Genes involved in androgen regulation, metabolism and their
      related pathways, and the vitamin D receptor are prime candidates for study of
      prostate cancer risk. Expression and nuclear activation of the VDR are necessary
      for the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 (calcitriol),
      which is involved in calcium and bone homeostasis. Several genetic variations
      have been identified in the VDR, and at least 1 VDR polymorphism appears to
      confer some predictability of prostate cancer risk in various ethnic cohorts.
      Interactions between the androgen receptor and circulating androgens have a major
      role in the development of normal and malignant prostate cells. CONCLUSIONS: Due
      to the relationship between the AR and prostatic growth, it has been proposed
      that polymorphisms within the AR may have a role in susceptibility to prostate
      cancer.

PMID- 14713752
TI  - Novel therapeutic molecular targets for prostate cancer: the mTOR signaling
      pathway and epidermal growth factor receptor.
AB  - PURPOSE: The scientific rationale and existing evidence for the use of novel
      molecular targets in the chemoprevention of cancer are reviewed, with special
      attention to prostate cancer. MATERIALS AND METHODS: A search for relevant
      literature on basic science and clinical trials was conducted using
      PubMed/MEDLINE. RESULTS: The emergence of molecularly targeted therapies for
      advanced malignancies creates an important opportunity to examine these agents
      for the chemoprevention of prostate cancer. Two critical targets in the
      proliferation and malignant transformation of normal cells, the PI3/Akt signal
      transduction pathway and the epidermal growth factor receptor, are currently the
      focus of several novel investigational therapies that are in late stage phase II
      and phase III studies. CONCLUSIONS: Research to date supports consideration of
      these novel molecular targets as future agents in the chemoprevention of prostate
      cancer.

PMID- 14713754
TI  - Selenium: epidemiology and basic science.
AB  - PURPOSE: The trace element selenium, a constituent of antioxidant enzymes, has
      been proposed as a chemopreventive agent for prostate and other cancers.
      MATERIALS AND METHODS: Published epidemiological and scientific studies relating
      to the potential clinical and molecular role of selenium in preventing cancer are
      reviewed and summarized. A unifying hypothesis underlying observations on the
      effect of selenium on early events in carcinogenesis is presented. RESULTS: A
      large body of epidemiological evidence, including observational, case-control,
      cohort and randomized controlled clinical trials, support the proposition that
      selenium may prevent prostate cancer in humans. The available data suggest a
      beneficial effect for men with low baseline serum or toenail selenium levels,
      without preexisting tumors, with serum prostate specific antigen less than 4
      ng/ml and in current or former smokers. Molecular data demonstrate that selenium
      prevents clonal expansion of nascent tumors by causing cell cycle arrest,
      promoting apoptosis, and modulating p53 dependent DNA repair mechanisms.
      CONCLUSIONS: These observations give strong scientific support to ongoing
      clinical trials testing the ability of selenium to prevent prostate cancer and
      the progression of high grade prostatic intraepithelial neoplasia to cancer.

PMID- 14713755
TI  - Vitamin A, retinoids and carotenoids as chemopreventive agents for prostate
      cancer.
AB  - PURPOSE: Evidence is examined for the use of vitamin A, retinoids and carotenoids
      as chemopreventive agents for prostate cancer. MATERIALS AND METHODS: Studies in
      in vitro and animal experimental models as well as in human observational
      (epidemiologic) and experimental studies are reviewed. RESULTS: There is little
      evidence that dietary vitamin A is associated with prostate cancer risk and,
      thus, it is unlikely that vitamin A or retinyl palmitate, the form most often
      used in dietary supplements, would be useful as chemoprevention agents. Several
      pharmaceutical formulations of retinoids show cancer prevention properties in
      animal experimental models but their high toxicity makes them unlikely candidates
      for cancer prevention. There is also currently no evidence that dietary
      carotenoids (except for lycopene and possibly other bioactive compounds found in
      tomato products) will be useful for prostate cancer prevention. Epidemiological
      and experimental studies show no association of beta-carotene with prostate
      cancer risk. There is inconsistent though intriguing evidence from
      epidemiological studies that tomato products and/or lycopene is associated with
      reduced prostate cancer risk. However, animal experimental studies of lycopene
      and prostate cancer are not strongly supportive, and the results of human
      experimental studies are not interpretable due to poor design. CONCLUSIONS: There
      is currently no evidence that vitamin A, synthetic retinoids or carotenoids can
      be used as prostate cancer chemopreventive agents. Experimental studies are
      needed to determine whether lycopene or other compounds in tomatoes have
      chemopreventive properties.

PMID- 14713756
TI  - Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective inhibitors
      for prostate cancer chemoprevention.
AB  - PURPOSE: There is increasing evidence that using nonsteroidal anti-inflammatory
      drugs decreases the incidence of clinically apparent prostate cancer. We review
      the potential mechanisms of cancer reduction with cyclooxygenase (COX)-2
      inhibitors and the clinical evidence suggesting their effectiveness. MATERIALS
      AND METHODS: A literature review using MEDLINE was conducted of animal,
      observational, and clinical studies of nonsteroidal anti-inflammatory drugs in
      cancer, specifically prostate cancer. The Physician Data Query database was
      searched for current studies of COX-2 inhibitors for chemoprevention of prostate
      cancer. RESULTS: Research suggests that COX-2 inhibiting medications are
      determinants in lower cancer incidence rates. Other studies have suggested up
      regulation of the COX-2 enzyme in prostate cancer compared with normal prostate
      tissue. Selective COX-2 inhibitors are currently under study to evaluate their
      potential roles in preventing prostate cancer in high-risk patients (rofecoxib)
      or the recurrence of bladder cancer (celecoxib). Agents such as exisulind, which
      is a selective apoptotic antineoplastic drug, are also under investigation.
      CONCLUSION: COX-2 inhibitors are promising agents for the chemoprevention of
      prostate cancer but further research is needed.

PMID- 14713757
TI  - Statistical design issues and other practical considerations for conducting phase
      III prostate cancer prevention trials.
AB  - PURPOSE: We briefly describe the purpose of phase II studies as a source of
      preliminary data for phase III prevention trials, and address statistical and
      other practical considerations for phase III prostate cancer prevention trials.
      MATERIALS AND METHODS: Objectives of 2 types of phase II studies and general
      criteria for validating surrogate end points are described, and statistical
      considerations needed for planning a phase III prevention trial are explained,
      including selection of an appropriate study population and end point, the
      corresponding expected event rate, estimates of loss to followup, and death and
      compliance rates. If a preventive agent has an impact on the ability to detect
      prostate cancer, additional study design considerations are then made. Other
      practical issues are addressed, including collection of biological materials for
      correlative studies, assessment of quality of life measures and the addition of
      ancillary studies that may include the collection of additional end points
      unrelated to prostate cancer. RESULTS: The Southwest Oncology Group is
      coordinating 2 recently reported phase III prostate cancer prevention trials. The
      Prostate Cancer Prevention Trial final results of 18,882 men randomized to either
      finasteride or placebo, and the Selenium and Vitamin E Cancer Prevention Trial
      has accrued more than half of its goal of 32,400 men. These studies are used to
      illustrate some statistical design features. CONCLUSIONS: The aforementioned
      trials provide valuable lessons in the successful design and conduct of phase III
      prostate cancer prevention trials.

PMID- 14713758
TI  - Prostate cancer chemoprevention agent development: the National Cancer Institute,
      Division of Cancer Prevention portfolio.
AB  - PURPOSE: We describe the current National Cancer Institute chemoprevention agent
      development program and provide a summary of the intermediate end points used.
      MATERIALS AND METHODS: The National Cancer Institute is currently sponsoring a
      wide range of studies of promising chemoprevention agents in a variety of
      informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive
      family history of cancer, increased prostate specific antigen with negative
      biopsies, prostate cancer followed expectantly, prostate cancer awaiting
      definitive therapy and the general population. The rationale for each agent under
      investigation is derived from epidemiological observations, prostate cancer
      treatment trials, secondary analyses of large cancer prevention studies, an
      understanding of cancer biology and prostate carcinogenesis, and/or experimental
      animal models. RESULTS: Carcinogenesis is a multistep process occurring over
      decades which is characterized by disruption of the normal regulatory pathways
      controlling cellular proliferation, programmed cell death and differentiation.
      Administration of agents to reverse, inhibit or slow this process of malignant
      transformation is known as chemoprevention. CONCLUSIONS: Chemoprevention
      represents a promising approach to reducing the morbidity and mortality of
      prostate cancer. A variety of agents are currently being studied in phase 2
      clinical trials, some of which may warrant subsequent evaluation in phase 3
      trials with definitive cancer end points. Two large phase 3 trials, the Prostate
      Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial,
      which are ongoing, are also sponsored by the National Cancer Institute.

PMID- 14713759
TI  - Emerging nephron sparing treatments for kidney tumors: a continuum of modalities
      from energy ablation to laparoscopic partial nephrectomy.
AB  - PURPOSE: The current global medical trend toward minimally invasive treatment for
      various tumors has generated special interest in several minimally invasive
      options in the management of kidney tumors. We discuss the role of nephron
      sparing surgery by less invasive options than the time-honored partial
      nephrectomy, and the current multitude of energy based tumor ablative methods.
      MATERIALS AND METHODS: We searched the English literature following the
      introduction of nephron sparing surgery, with special attention to various
      emerging minimally invasive surgical and ablative alternatives. RESULTS:
      Laparoscopic partial nephrectomy can be performed safely following the surgical
      oncology principles established by open partial nephrectomy. Initial results from
      the various energy based modalities, most notably cryoablation, indicate that
      high local control rates can be achieved. However, caution is advised since
      viable tissue has been observed after minimally invasive ablative therapies.
      Available data, while promising, are still lacking for long-term followup.
      CONCLUSIONS: Compared to open partial nephrectomy the laparoscopic approach
      offers similar cancer-free survival rates. However, the procedure requires highly
      skilled surgeons. Of the energy based ablative treatments cryoablation followed
      by radio frequency ablation offers the most meaningful results, with promising
      local control rates indicated in some series. These methods can be performed less
      invasively than partial nephrectomy and require less surgical expertise. We
      anticipate that these modalities will be formalized into urological practice and
      serve as a single continuum of care, customized according to disease and surgical
      expertise.

PMID- 14713760
TI  - Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a
      systematic review and meta-analysis.
AB  - PURPOSE: Despite local therapy most patients with muscle invasive transitional
      cell carcinoma (TCC) of the bladder die of systemic relapse, indicating a need
      for effective adjunctive systemic treatment. We determined whether neoadjuvant
      chemotherapy improved overall survival. MATERIALS AND METHODS: A systematic
      review and meta-analysis were performed of all known randomized controlled trials
      (RCTs) of neoadjuvant chemotherapy for stages II and III TCC conducted between
      1984 and 2002. RESULTS: A total of 16 eligible RCTs (3,315 patients) were
      identified. Of these trials 11 (2,605 patients) provided data suitable for a meta
      analysis of overall survival and the pooled HR was 0.90 (95% CI 0.82 to 0.99, p =
      0.02). Eight trials used cisplatin based combination chemotherapy and the pooled
      HR was 0.87 (95% CI 0.78 to 0.96, p = 0.006), consistent with an absolute overall
      survival benefit of 6.5% (95% CI 2 to 11%) from 50% to 56.5%. Reported
      progression-free survival data were insufficient for meta-analysis but they
      appeared concordant with overall survival results. Mortality due to combination
      chemotherapy was 1.1%. A major pathological response was associated with improved
      overall survival in 4 trials. CONCLUSIONS Neoadjuvant cisplatin based
      chemotherapy improves overall survival in muscle invasive TCC. The size of the
      effect is modest and combination chemotherapy can be administered safely without
      adverse outcomes resulting in delayed local therapy. An optimal chemotherapy
      regimen was not identified and newer regimens have not been tested in RCTs in
      this setting. Further efforts to identify the patients most likely to benefit
      from neoadjuvant therapy are necessary to optimize its use.

PMID- 14713761
TI  - Correlation of metastasis related gene expression and relapse-free survival in
      patients with locally advanced bladder cancer treated with cystectomy and
      chemotherapy.
AB  - PURPOSE: Patients with locally advanced (ie clinically extravesical) transitional
      cell carcinoma are at high risk for recurrence after cystectomy. Although
      randomized trials have established an incremental benefit from the addition of
      chemotherapy in this setting, many patients still have disease relapse, and
      therefore it is necessary to determine patient and tumor characteristics that
      correlate with outcome in this setting. We investigated the tumor expression of
      several metastasis related genes and the association of gene expression with
      disease specific survival of patients with locally advanced transitional cell
      carcinoma treated randomized to either neoadjuvant or adjuvant chemotherapy and
      radical cystectomy. MATERIALS AND METHODS: Archival paraffin embedded specimens
      were available for 64 patients enrolled in a clinical trial of the methotrexate,
      vinblastine, doxorubicin and cisplatin regimen and cystectomy. Only samples
      obtained before exposure to chemotherapy were studied. The expression of several
      metastasis related genes, including basic fibroblast growth factor, vascular
      endothelial growth factor (VEGF), interleukin-8, matrix metalloproteinase (MMP)
      9, and E-cadherin were assayed on paraffin sections using a colorimetric in situ
      hybridization assay. RESULTS: Expression of basic fibroblast growth factor,
      interleukin-8 and MMP-9 did not correlate with outcome. Expression of VEGF and E
      cadherin were strongly related to disease specific survival. In addition, the
      ratio of MMP-9-to-E-cadherin was strongly prognostic for disease specific
      survival. CONCLUSIONS: These data advance the hypotheses that VEGF expression and
      an "invasive phenotype" characterized by the ratio of MMP-9-to-E-cadherin
      expression are mechanistically relevant to clinically aggressive locally advanced
      bladder cancers that are not cured by currently available combined modality
      treatment. Thus, in our view there is a compelling rationale to target these
      aspects of the malignant phenotype in this patient population.

PMID- 14713763
TI  - Ureteropelvic junction obstruction: determining durability of endourological
      intervention.
AB  - PURPOSE: We evaluated the durability of endourological intervention for
      ureteropelvic junction obstruction and established guidelines for postoperative
      surveillance. MATERIALS AND METHODS: Since 1989, 150 patients have undergone
      endourological intervention for ureteropelvic junction obstruction, of whom 127
      (53 men and 74 women) 13 to 79 years old (mean age 40.4) underwent postoperative
      evaluation at our center. These 127 patients are the study group reported.
      Endourological management consisted of hot wire balloon endopyelotomy in 25
      patients, percutaneous endopyelotomy in 67 and ureteroscopic laser endopyelotomy
      in 35. Success in this study was strictly defined as symptomatic relief plus
      radiographic resolution on excretory urogram and/or diuretic renogram.
      Statistical analysis was performed to assess mean time to failure and develop
      Kaplan-Meier re-stenosis-free survival estimates. RESULTS: Followup was 1 to 128
      months (mean 22). Time to failure was 0.9 to 32.4 months (mean +/- SD 10.3 +/-
      9.4). Kaplan-Meier estimates of time to re-stenosis (failure) were 6 months in
      12% of patients, 12 in 22%, 18 in 24%, 24 in 27%, 30 in 32% and 36 in 37%. After
      3 years no further failures were observed and Kaplan-Meier estimates remained
      unchanged. CONCLUSIONS: The long-term probability of success, which is estimated
      to be 63.3% in this series, is somewhat lower than that reported in the
      literature. It likely is a result of longer followup and a more strict definition
      of success that includes functional and symptomatic relief. Our data suggest that
      while most failures become evident within the first 12 months, failure can
      develop as late as 3 years after intervention. As such, patients should be
      followed at least that long to ensure a durable result.

PMID- 14713762
TI  - Sealing percutaneous nephrolithotomy tracts with gelatin matrix hemostatic
      sealant: initial clinical use.
AB  - PURPOSE: Tubeless percutaneous nephrolithotomy (PCNL) has been performed at
      several centers with good success. However, these cases have been carefully
      selected with regard to short duration and smaller stone burden to prevent
      complications associated with the loss of access to the collecting system. We
      describe the use of gelatin matrix hemostatic sealant (FloSeal Baxter Medical,
      Fremont, California) as an adjunct to tubeless percutaneous nephrolithotomy to
      help preclude bleeding complications. MATERIALS AND METHODS: Two patients were
      treated with PCNL through a single nephrostomy tract. At the satisfactory
      conclusion of the cases the tract was occluded retrograde with an occlusion
      balloon catheter and gelatin matrix hemostatic sealant was injected down the
      nephrostomy tract. An indwelling stent and bladder catheter were placed following
      which all guidewires were removed and skin sutures were placed. RESULTS: The
      operative times were 75 and 180 minutes, respectively. Both patients had stable
      postoperative hemoglobin and no evidence of bleeding or obstruction on
      postoperative computerized tomography. CONCLUSIONS: Injection of gelatin matrix
      hemostatic sealant into the nephrostomy tract may be of value in preventing
      bleeding after PCNL. In this pilot experience it provided immediate and effective
      hemostasis.

PMID- 14713764
TI  - Long-term outcome of laparoscopic decortication of peripheral and peripelvic
      renal and adrenal cysts.
AB  - PURPOSE: We determined the perioperative course of laparoscopic decortication of
      renal/adrenal cysts, and the association among cyst location, radiographic
      assessment and long-term symptom relief. MATERIALS AND METHODS: Laparoscopic cyst
      decortication was performed 18 times in 17 patients for pain relief (1 patient
      had bilateral cysts) at our institution between August 1996 and June 1999. Of
      these patients 13 had single and 5 had multiple cysts, and 9 each had peripelvic
      and peripheral (includes 2 adrenal) cysts. Questionnaires were prospectively
      distributed to these patients preoperatively, 2 and 6 weeks postoperatively, and
      annually thereafter. Preoperative and postoperative radiographs were reviewed.
      RESULTS: Perioperative morbidity measures were similar to those previously
      published with minimal complications and a rapid recovery. Cyst location had no
      significant perioperative impact. Symptom relief occurred in 78% of cases
      overall. Median final symptomatic followup was 52 months. Radiographic success
      (complete absence of cyst) was 89% for the peripheral cyst group and 55% for the
      peripelvic cyst group (p = 0.29). Median radiographic followup was 23 months.
      Symptomatic failure occurred in 40% of the 5 radiographic failures and 15% of the
      13 radiographic successes (p = 0.53). CONCLUSIONS: Laparoscopic decortication is
      a safe, minimally invasive and effective treatment for symptomatic renal cysts
      with durable response. Although peripelvic cyst location can make certain cases
      more difficult or even technically not feasible, perioperative measures and long
      term outcome are generally equivalent. Symptomatic failure after complete cyst
      resection, as measured radiographically, is likely due to a misdiagnosis of the
      cause of symptoms.

PMID- 14713765
TI  - Prognostic significance of venous thrombus in renal cell carcinoma. Are renal
      vein and inferior vena cava involvement different?
AB  - PURPOSE: The prognostic significance of the level of venous involvement in renal
      cell carcinoma (RCC) is controversial. It has been suggested that the 1997 TNM
      classification of venous involvement system should be revised. MATERIALS AND
      METHODS: The records of 226 patients who underwent a nephrectomy and tumor
      thrombectomy, 117 for renal vein (RV) and 109 for inferior vena cava (IVC)
      involvement, between 1989 and 2001 were reviewed and compared to those of 654
      patients undergoing nephrectomy without venous involvement. RESULTS: In patients
      with localized RCC (N0M0), the risk of recurrence after nephrectomy was
      significantly increased in patients with venous thrombus compared to patients
      without venous thrombus (p = 0.005). However, the difference was not significant
      in a multivariate analysis including T stage (1, 2, 3 or 4), Fuhrman grade and
      Eastern Cooperative Oncology Group performance status. In patients with localized
      RCC disease specific survival was similar (p = 0.536) in patients with RV (T3b)
      and IVC involvement below the diaphragm (T3b). However, patients with IVC
      involvement above the diaphragm (T3c) had a significantly worse survival rate
      even after controlling for Fuhrman grade and Eastern Cooperative Oncology Group
      performance status in a multivariate analysis (p = 0.020). All patients treated
      for metastatic RCC had a similar prognosis regardless of the level of venous
      involvement. CONCLUSIONS: For patients with pT3b disease, local tumor stage and
      grade are better predictors of prognosis than extent of venous involvement. Based
      on our data we support the current TNM classification of venous involvement with
      RV and IVC invasion categorized as T3b and IVC involvement above the diaphragm
      categorized as T3c.

PMID- 14713766
TI  - Residency training in percutaneous renal access: does it affect urological
      practice?
AB  - PURPOSE: We evaluated the impact of residency training in percutaneous renal
      access on subsequent urological practice. MATERIALS AND METHODS: Surveys
      evaluating practice and training in percutaneous renal access were mailed to
      residents who graduated between 1981 and 2001. A statistical analysis was
      performed to determine the effect of percutaneous access training on current
      practice patterns in percutaneous renal procedures. A subgroup analysis was
      conducted for graduates with more than 10 years after residency. RESULTS:
      Responses were received from 37 of 48 surveys mailed (77%) and 35 surveys were
      eligible for analysis. A total of 92% of urologists trained in percutaneous
      access currently perform percutaneous surgical procedures compared to only 33% of
      those untrained (p <0.001). Urologists trained in access perform a mean of 14.0
      percutaneous renal procedures annually while those untrained perform 3.3
      procedures (p = 0.02). Only 27% of urologists trained in percutaneous access
      continue to perform percutaneous renal access compared to 11% of those untrained
      (p = 0.33). A subset analysis of urologists trained more than 10 years ago shows
      similar results. The primary reasons stated for not performing their own access
      are that the radiologist has better equipment (61%) or skills (44%), or obtaining
      access requires extra time (50%). CONCLUSIONS: This study suggests a relationship
      between training in percutaneous renal access and subsequent use of percutaneous
      renal procedures in the urologist's practice. Emphasis should be placed on
      providing continuing education opportunities to maintain competency in this
      important technique.

PMID- 14713767
TI  - Kidney surgery at the start of the 21st century.

PMID- 14713768
TI  - Prognostic significance of tumor thrombus level in patients with renal cell
      carcinoma and venous tumor thrombus extension. Is all T3b the same?
AB  - PURPOSE: We investigated the prognostic significance of venous tumor thrombus
      extension in patients with renal cell carcinoma with particular emphasis on 2
      questions. Does the level of thrombus in the inferior vena cava (IVC) impact long
      term survival? Is there a difference in long-term survival when tumor thrombus is
      in the renal vein versus the IVC for patients classified as T3b by 1997 TNM
      staging? MATERIALS AND METHODS: Between July 1970 and July 2000, 153 patients
      underwent surgical resection. Cancer specific survival was determined for
      different tumor thrombus levels in a retrospective fashion. RESULTS: Mean
      followup was 60 months with a range of 12 to 221. Level of tumor thrombus was
      renal vein (in 46), level I (in 68), level II (in 17) and level III (in 22). No
      demographic differences existed between the different levels including gender,
      age, perinephric extension, Fuhrman grade, percentage of metastatic disease and
      tumor size (Fisher's exact test). Patients with evidence of nodal disease or
      metastasis at surgery were eliminated from cancer specific survival analysis. The
      overall 10-year cancer specific survival for patients was 30%, 19% and 29% for
      level I, II and III, respectively. Patient survival at 5 and 10 years was not
      significantly different between the 3 IVC levels (p = 0.48). Ten-year survival of
      patients with renal vein involvement (66%) versus level I (29%) was significantly
      different (p = 0.0001). CONCLUSIONS: The level of tumor thrombus in the IVC does
      not significantly effect long-term survival. Ten-year survival of patients
      classified as T3b is statistically different for patients having tumor thrombus
      in the renal vein compared to level I. Combining these 2 groups as T3b by the
      1997 TNM staging may need to be reevaluated.

PMID- 14713769
TI  - Cytogenetic analysis of a series of 13 renal oncocytomas.
AB  - PURPOSE: Only about 50 renal oncocytomas have been studied cytogenetically. They
      fall into 3 categories, namely 1-normal karyotype, 2-monosomy 1, often with Y
      chromosome loss, and 3-structural abnormalities of 11q13. Additional
      abnormalities may occur with transformation to chromophobe renal cell carcinoma,
      although exactly which one is unclear. We expanded the oncocytoma data base to
      shed light on changes that characterize transformation. MATERIALS AND METHODS: A
      total of 14 oncocytomas from 12 patients were collected in 2(1/2) years. One
      tumor failed to grow but 13 were successfully karyotyped. RESULTS: Seven tumors
      (53.8%), including 2 from 1 kidney, had normal karyotypes or abnormalities
      characteristic of normal kidney tissue. A total of 6 tumors from 5 individuals
      (46.2%) had chromosome 1 abnormalities. Monosomy 1 was detected in 2 single
      tumors and in both tumors in a bilateral case. Structural anomalies resulting in
      loss of the short arm of chromosome 1 were found in an additional 2 patients.
      Other abnormalities, including Y chromosome loss and monosomy 14, were observed
      but no abnormalities of 11q13 were seen. CONCLUSIONS: Our series confirms that 1p
      loss is the most common anomaly in oncocytoma. Additional studies are required to
      understand the transformation potential of this usually benign tumor, identify
      the putative 1p tumor suppressor gene and determine whether karyotypically normal
      tumors have molecular abnormalities of 1p.

PMID- 14713770
TI  - Significance of orotate phosphoribosyltransferase activity in renal cell
      carcinoma.
AB  - PURPOSE: The anticancer agent 5-fluorouracil (5-FU) is clinically used against
      various cancers, including renal cell carcinoma (RCC). It is a prodrug and
      orotate phosphoribosyltransferase (OPRT) is the principal enzyme that directly
      converts 5-FU to the active anticancer metabolite 5-fluoro-2'-deoxyuridine 5'
      monophosphate. In addition, OPRT is the key enzyme in the de novo DNA and RNA
      synthetic process. Little is known about the significance of OPRT in various
      cancers, including RCC. We investigated the activity of OPRT in 83 RCCs and
      evaluated the association between the level of OPRT activity and the stage/grade
      of RCC. The relationship between OPRT activity in RCC cells and their sensitivity
      to 5-FU was also examined. MATERIALS AND METHODS: OPRT activity in nonfixed,
      fresh frozen RCC and normal kidney was determined enzymatically by the 5-FU
      phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the
      microculture tetrazolium dye assay. RESULTS: The activity of OPRT was
      approximately 8.5-fold higher in RCC than in normal kidney. OPRT activity in
      stage III/IV RCC was 3-fold higher than in stage I/II RCC. The level of OPRT
      activity in grade 3 RCC was 3-fold higher than that in grade 1/2 cancer. Patients
      with RCC with low OPRT activity had longer postoperative disease specific
      survival than those with high activity at 5-year followup. OPRT activity in RCC
      cells positively correlated with their sensitivity to 5-FU. CONCLUSIONS: To our
      knowledge this is the first study to demonstrate that OPRT activity in RCC was
      higher than that in normal kidney and OPRT activity positively correlated with
      RCC stage/grade. In addition, higher OPRT activity in RCC predicted worse
      prognosis and higher sensitivity to 5-FU. These results suggest that the level of
      OPRT activity may be used as a prognostic parameter and predictive indicator for
      5-FU efficacy in RCC and OPRT may be a molecular therapeutic target in RCC.

PMID- 14713771
TI  - Steroid hormone receptor expression in renal cell carcinoma: an
      immunohistochemical analysis of 182 tumors.
AB  - PURPOSE: Steroid hormone receptor expression has an essential role in cancer of
      the prostate and breast but there is only limited experience with renal cell
      carcinoma (RCC), especially regarding prognostic and therapeutic impact.
      MATERIALS AND METHODS: A total of 188 cases of RCC were stained
      immunohistochemically for the expression of estrogen (ER), progesterone (PR) and
      androgen (AR) receptors using a tissue microarray technique. Nuclear steroid
      hormone receptor immunoreactivities were analyzed semiquantitatively with respect
      to associations with histological subtype, pT stage, grading and gender using
      Fisher's exact test. Impact on disease-free survival was analyzed using the
      Kaplan-Meier method. RESULTS: Sufficient tumor tissue was present in 182 of the
      188 RCCs. AR expression was found in 27 of 182 tumors (14.8%) in 24 male and 3
      female patients. AR expression was significantly associated with stage pT1
      compared with pT3 (p <0.0001), and grades 1 and 2 compared with grade 3 (p =
      0.0005). Regarding progression-free survival, AR positive RCCs showed a
      significantly better prognosis than AR negative cases (log rank test, p = 0.027).
      No difference of AR immunoreactivity could be detected between histological
      subtypes. Only 2 of the 182 cases (1.1%) showed ER and PR immunoreactivity in
      less than 10% of tumor cell nuclei. CONCLUSIONS: While ER and PR expression was
      the exception, AR expression was found in almost 15% of the tumors and it was
      significantly associated with low stage, well or moderately differentiated tumors
      and a favorable outcome, decreasing with tumor growth and dedifferentiation.
      However, these results do not support a potential role of hormonal therapy for
      metastatic RCC.

PMID- 14713772
TI  - Multifocal renal cortical tumors: frequency, associated clinicopathological
      features and impact on survival.
AB  - PURPOSE: We determined the frequency of tumor multifocality in patients with
      renal cortical tumors, characterized clinical and pathological features
      associated with multifocality and evaluated its effect on patient survival.
      MATERIALS AND METHODS: Between July 1989 and July 2002, 1,071 radical
      nephrectomies were performed at our institution. Specimens were examined grossly
      and microscopically for multifocal tumors. Preoperative imaging was reviewed to
      determine whether multifocality was suspected prior to operation. Multivariate
      analysis was performed to identify clinical and pathological factors associated
      with multifocality. RESULTS: Of 1,071 radical nephrectomy specimens 57 (5.3%) had
      pathological evidence of tumor multifocality. Bilateral synchronous renal
      cortical tumors were present in 6 of the 57 multifocal cases (11%). A total of 19
      cases (33%) had evidence of multifocality on preoperative imaging and, therefore,
      occult multifocality undetected on preoperative imaging was present in 3.5% of
      radical nephrectomies (38 of 1,071). Primary tumors in the multifocal group were
      most commonly conventional clear cell carcinoma, followed by papillary carcinoma.
      Of multifocal cases 74% had the same histological subtype in all tumors.
      Multivariate analysis demonstrated that bilaterality, papillary subtype, advanced
      tumor stage and lymph node metastasis were associated with multifocality. At a
      median follow up of 40.5 months overall survival, disease-free survival, and
      disease-free probability were not significantly different between the multifocal
      and unifocal groups. CONCLUSIONS: We report a 5.3% frequency of multifocal renal
      cortical tumors and a 3.5% frequency of clinically unsuspected multifocal tumors.
      Multifocality had no apparent effect on recurrence or survival in patients who
      underwent radical nephrectomy.

PMID- 14713773
TI  - The impact of tumor location on prognosis of transitional cell carcinoma of the
      upper urinary tract.
AB  - PURPOSE: We assessed the impact of traditional prognostic factors and tumor
      location on the survival of patients treated for upper tract transitional cell
      carcinoma (TCC). MATERIALS AND METHODS: We retrospectively analyzed the data on
      86 patients with upper tract TCC who underwent nephroureterectomy with a bladder
      cuff (95%) or parenchymal sparing surgery (5%). Mean patient age was 59.5 years
      and median followup was 43.8 months. The influence of traditional prognostic
      factors such as age, gender, tumor stage, grade and location on 5-year disease
      specific and recurrence-free (local recurrence or distant metastasis) survival
      rates was analyzed. The difference in survival rates between renal 45 pelvis and
      41 ureteral cases was analyzed according to the respective T stage and grade.
      RESULTS: Overall 5-year disease specific and recurrence-free survival rates were
      83% and 72%, respectively. The significant prognostic factors for survival rates
      by univariate analysis were T stage, grade and location. N stage was significant
      for 5-year recurrence-free survival. On multivariate analysis tumor location was
      the only independent prognostic factor for the 2 survival rates, while N stage
      was significant for 5-year recurrence-free survival. Patients with ureteral tumor
      had a worse prognosis than those with pelvis tumor at the same stage or grade (p
      = 0.036). CONCLUSIONS: Pelvis and ureteral TCC are not the same disease in terms
      of invasion and prognosis. Ureteral TCC is associated with a higher local or
      distant failure rate than renal pelvis TCC. A radical surgical approach including
      meticulous lymphadenectomy may be therapeutic in patients with invasive ureteral
      TCC.

PMID- 14713774
TI  - Urine detection of survivin is a sensitive marker for the noninvasive diagnosis
      of bladder cancer.
AB  - PURPOSE: In a preliminary study urine detection of survivin, an integrator of
      cell death and mitosis, accurately detected bladder cancer. The objectives of
      this study were to confirm these findings in a large cohort of subjects
      undergoing cystoscopy, to assess the diagnostic performance of urine survivin and
      to test whether evaluation of urine survivin adds independent value to urine
      NMP22 (Matritech, Cambridge, Massachusetts) and cytology for the detection of
      bladder cancer. MATERIALS AND METHODS: Urine survivin was measured using a Bio
      Dot microfiltration detection system (Bio-Rad, Hercules, California) in voided
      urine specimens collected before cystoscopy in 117 cases and 92 controls. Bladder
      washout samples for cytology were collected in 174 subjects. Urine levels of
      NMP22 were measured using a commercially available enzyme-linked immunosorbent
      assay. RESULTS: Higher levels of urine survivin were associated with an increased
      risk of bladder cancer (p <0.001) and tumors of higher grade (p = 0.037), but not
      with invasive stage, after adjustment for the effects of urine cytology, NMP22
      and age. The sensitivity, specificity, and positive and negative predictive
      values of survivin for the diagnosis of bladder cancer (64%, 93%, 92% and 67%,
      respectively), are superior to those of NMP22 and cytology. Survivin had the
      highest specificity and positive predictive value for the detection of bladder
      cancer across each tumor stage and grade. CONCLUSIONS: Urine survivin was a
      strong, independent predictor of the presence of bladder cancer and higher tumor
      grade. Urine detection of survivin is an accurate diagnostic test for bladder
      cancer that retains its efficiency regardless of cancer stage and grade.

PMID- 14713776
TI  - Efficacy of office fulguration for recurrent low grade papillary bladder tumors
      less than 0.5 cm.
AB  - PURPOSE: Recurrent superficial papillary bladder tumors are most commonly treated
      with transurethral resection with the patient under anesthesia. We report our
      experience with office fulguration of small, recurrent, low grade papillary
      tumors using flexible cystodiathermy. MATERIALS AND METHODS: We conducted a
      prospective single institution analysis of 267 consecutive patients with
      superficial bladder cancer undergoing routine bladder cancer surveillance between
      January 1998 and December 2001. Cytological and histological recurrences were
      recorded. Selection criteria for office fulguration were less than 5 low grade
      appearing papillary tumors, tumor size less than 0.5 cm, negative urine cytology
      and patient desire. All patients completed initial treatment (transurethral
      resection, partial cystectomy and/or intravesical therapy) and a minimum of 6
      months on surveillance without recurrence (median 11.57 months). RESULTS:
      Flexible cystodiathermy for small, low grade, recurrent papillary tumors was
      efficacious and well tolerated. Of the 123 patients 46% experienced 1 or more
      tumor recurrences (range 1 to 11) in a median followup of 2.6 years. Of these
      123, 74 (60%) underwent office cystodiathermy. No difference was seen in disease
      specific survival (p = 0.1633) or disease progression (p = 0.860). When
      stratified by risk of recurrence 202 of 267 patients at high risk (76%) with low
      grade papillary recurrence had similar rates of progression to patients at low
      risk (p = 0.9025). Median time from diagnosis was 6.84 years, and time from last
      tumor was 20.4 months. CONCLUSIONS: Office cystodiathermy of small, low grade
      papillary recurrence is safe and efficacious in properly selected patients. This
      change in practice can potentially improve patient quality of life and have a
      major economic impact on health care.

PMID- 14713775
TI  - Expression of survivin, a novel inhibitor of apoptosis, in superficial
      transitional cell carcinoma of the bladder.
AB  - PURPOSE: We investigated whether the over expression of survivin, a new
      antiapoptotic protein, might provide prognostic information in patients with
      superficial bladder cancer. MATERIALS AND METHODS: Immunohistochemical staining
      of paraffin sections using a monoclonal antibody for survivin was performed in 88
      cases of superficial bladder cancer using the standard avidin-biotin-peroxidase
      technique. The relationships between the expression of survivin,
      clinicopathological characteristics and clinical outcome were analyzed. RESULTS:
      Survivin expression was found in tumor cells but not in nonneoplastic bladder
      tissues. High expressions (greater than 20%) of survivin were observed in 51
      cases (58.0%) and low expression in 37 cases. No statistically significant
      association was observed between survivin expression and tumor grade (p = 0.052)
      or pathological stage (p = 0.131). When clinical data such as sex, age, tumor
      number, size or shape were examined in conjunction with survivin status no
      statistically significant relationship was noted. Patients with a high expression
      of survivin had worse disease-free survival rates than those with low survivin
      expression (log rank test p = 0.0004). Multivariate Cox proportional hazards
      model analysis identified survivin expression as an independent prognostic factor
      of disease-free survival (p = 0.009, relative risk = 3.17). CONCLUSIONS: Our
      findings suggest that high survivin expression may be considered a new
      unfavorable prognostic factor in superficial bladder cancer.

PMID- 14713777
TI  - Microscopic and gross extravesical extension in pathological staging of bladder
      cancer.
AB  - PURPOSE: We evaluated clinical outcomes in patients with pathological microscopic
      (pT3a) and gross (pT3b) extravesical tumor extension with transitional cell
      carcinoma (TCC) of the bladder following radical cystectomy. MATERIALS AND
      METHODS: A total of 236 patients, including 173 males (73%) and 63 females,
      underwent radical cystectomy for pathological primary bladder TCC with
      extravesical extension (pT3), of whom 69 (29%) had pT3a and 167 (71%) had pT3b
      disease. At a median followup of 8.9 years (range 0 to 19.4) lymph node
      involvement, local and distant recurrences, and clinical outcomes were
      determined. RESULTS: Of the 236 patients with pT3 tumors 106 (45%) had lymph node
      positive disease, including 34 of 69 (49%) with pT3a and 72 of 167 (43%) with
      pT3b disease. The 10-year recurrence-free survival rate for patients with pT3a
      tumors was 48% compared with 47% for those with pT3b disease (p = 0.89).
      Recurrence-free survival was significantly better in patients with lymph node
      negative disease than in those with positive lymph nodes irrespective of the
      extent of extravesical involvement (pT3a vs pT3b). Local pelvic recurrence
      developed in 13 of the 236 patients (6%), while 84 (36%) had distant metastatic
      disease. Of the patients with recurrence, the type of recurrence (local or
      distant) was not associated with tumor stage (pT3a vs pT3b, p = 0.71). Lymph node
      involvement was a significant risk factor for distant tumor recurrence (p
      <0.001). CONCLUSIONS: Differentiating between microscopic (pT3a) and gross (pT3b)
      extravesical tumor involvement of TCC as outlined in the revised 1997 TNM staging
      system does not appear to have prognostic significance.

PMID- 14713778
TI  - Incidence and location of prostate and urothelial carcinoma in prostates from
      cystoprostatectomies: implications for possible apical sparing surgery.
AB  - PURPOSE: Prostatic carcinoma (Pca) at cystoprostatectomy is usually an incidental
      finding with the majority thought to be clinically insignificant. Most studies
      have not specifically addressed the location of Pca or the incidence and location
      of in situ or invasive urothelial carcinoma (Uca) in prostates of
      cystoprostatectomy specimens. The frequency of involvement of the apex with these
      processes has clinical implications. Specifically urinary continence following
      orthotopic diversion may be enhanced by prostate apical sparing. In this study
      the pathological features of Pca and Uca, and the frequency of apical involvement
      were investigated in prostates from cystoprostatectomy specimens. MATERIALS AND
      METHODS: Whole mounted prostates from 121 consecutive cystoprostatectomy
      specimens were analyzed. Pca location, tumor volume, grade, stage, surgical
      margin and pelvic lymph node status of Pcas were assessed. Clinically
      insignificant Pcas had a volume of less than 0.5 cc without Gleason pattern 4,
      extracapsular extension, seminal vesicle invasion, lymph node involvement or
      positive surgical margins. Prostate involvement by Uca or urothelial carcinoma in
      situ (CIS)/severe dysplasia and its location were assessed. RESULTS: Of 121
      prostates 50 (41%) had unsuspected Pca, of which 24 (48%) were clinically
      significant. Of Pcas 30 of 50 (60%) involved the apex, including 19 of 24 (79%)
      that were significant and 11 of 26 (42%) that were insignificant. Of 121
      prostates 58 (48%) had Uca involving the prostatic stroma, noninvasive Uca or
      urothelial CIS/severe dysplasia in the prostatic urethra or periurethral ducts,
      of which 19 (33%) had apical involvement. Overall only 32 of 121 patients (26%)
      had no Pca or prostate Uca/CIS and only 45 (37%) had no clinically significant
      Pca or Uca/CIS in the prostate. However, 74 of the 121 patients (61%) had no
      prostatic apical involvement by Pca or Uca/CIS and 85 (70%) had no apical
      involvement by clinically significant Pca or Uca/CIS. Patients with prostatic
      apical involvement by invasive or in situ Uca uniformly had involvement of more
      proximal (toward the base) portions of the prostate. CONCLUSIONS: The majority of
      prostates from cystoprostatectomies had no involvement of the prostatic apex by
      Uca or clinically significant Pca. Hence, most patients may be candidates for
      prostate apical sparing. However, involvement of the apex by Uca in any patient
      raises concern about procedures that leave portions of the prostate urethra after
      cystectomy in an effort to improve continence. In candidates for orthotopic
      neobladder reconstruction removing all of the prostatic urethra and sparing the
      remainder of the prostatic apex may allow improved preservation of urinary
      continence with an acceptable low risk of clinical Pca progression. Whether
      future strategies for preoperative exclusion of apical Pca and intraoperative
      assessment of more proximal prostate to help exclude apical urothelial disease
      may identify patients suitable for prostatic apical sparing remains to be
      determined. The impact on functional outcomes and cancer control also require
      additional study.

PMID- 14713779
TI  - Association among an ornithine decarboxylase polymorphism, androgen receptor gene
      (CAG) repeat length and prostate cancer risk.
AB  - PURPOSE: A single nucleotide substitution of guanine to adenine (A) at base +316
      in the ornithine decarboxylase (ODC) gene may be associated with greater ODC
      expression and increased tumor growth. ODC is induced by androgens in human
      prostatic epithelial cells, presumably via transcriptional activation of androgen
      receptor (AR) and also by nicotine. A nested case-control study was done to
      examine the association between this ODC genotype and prostate cancer risk, and
      whether it varies by AR gene CAG repeat length and smoking. MATERIALS AND
      METHODS: A total of 164 cases were matched to 2 controls each from a community
      based cohort. ODC and AR genotyping was performed using a TaqMan (PE Applied
      Biosystems, Foster City, California) based assay and automated fragment analysis,
      respectively. Conditional logistic regression was used to estimate the OR and 95%
      CI. RESULTS: The presence of the ODC A allele was not significantly associated
      with an increased risk of prostate cancer (OR 1.33, 95% CI 0.90 to 1.96).
      However, men who inherited at least 1 ODC A alleles and less than 22 AR CAG
      repeats were at twice the risk of prostate cancer compared with those with 2
      guanine alleles and 22 or greater AR CAG repeats (OR 2.09, 95% CI 1.23 to 3.57).
      Smoking was associated with prostate cancer only in men carrying a least 1 ODC A
      allele (p interaction = 0.02). CONCLUSIONS: The ODC A allele was not associated
      with a statistically significant increased risk of prostate cancer. However, this
      association may vary according to the number of CAG repeats in the AR receptor
      and smoking status.

PMID- 14713780
TI  - The risk of rapid prostate specific antigen increase in men with baseline
      prostate specific antigen 2.0 ng/ml or less.
AB  - PURPOSE: We estimated the risk of a rapid prostate specific antigen (PSA)
      increase in men with a low baseline PSA range of 0.0 to 2.0 ng/ml to investigate
      the validity of setting a re-screening interval of more than 1 year. MATERIALS
      AND METHODS: Between 1988 and 1999, 6,252 men with baseline PSA 2.0 ng/ml or less
      without suspicious findings on digital rectal examination (DRE) and 7,304 with
      the same baseline PSA who did not undergo DRE at the time of baseline PSA
      measurement were re-screened. The risks of a PSA increase to 4.1 to 10.0, 10.1 to
      20.0 and greater than 20.0 ng/ml were investigated and stratified by re-screening
      interval, baseline DRE status, and subdivided baseline PSA ranges of 0.0 to 1.0
      and 1.1 to 2.0 ng/ml. RESULTS: A total of 28 cases (0.2% of 13,556) of prostate
      cancer were detected after an average re-screening interval of 3.6 years. High
      PSA above 10 ng/ml at diagnosis was noted in 5 patients (18%), including 2 with a
      great PSA increase to 1,928 and 298 ng/ml at re-screening intervals of 4 and 6
      years, respectively. CONCLUSIONS: Setting 4 to 5-year re-screening intervals for
      PSA measurements in men with PSA 1.0 ng/ml or less can decrease the cost of PSA
      tests without lowering sensitivity. A re-screening interval for PSA measurement
      should be set annually for men with PSA 1.1 to 2.0 ng/ml to minimize the risk of
      missing aggressive cancer.

PMID- 14713781
TI  - Clinical value of longitudinal free-to-total prostate specific antigen ratio
      slope to diagnosis of prostate cancer.
AB  - PURPOSE: Free and total serum prostate specific antigen (PSA) levels are
      frequently used for early prostate cancer detection in men with a total PSA in
      the 2.6 to 10 ng/ml range. Results from a longitudinal study suggested that the
      free-to-total PSA ratio (F/T PSA), declining the decade before prostate cancer
      diagnosis, is the earliest serum marker predicting a subsequent diagnosis of
      prostate cancer. Other than this study, there are limited data on the predictive
      value of longitudinal F/T PSA measurements for subsequent cancer. To evaluate the
      clinical importance of a decreasing F/T PSA, we compared longitudinal F/T PSA in
      volunteers in a prostate cancer screening study. MATERIALS AND METHODS: We
      evaluated 657 volunteers in a screening study with a total PSA of 2.6 to 10 ng/ml
      but whose initial biopsies were either negative for cancer or were waived. To
      obtain meaningful F/T PSA slopes, the patients have been followed with at least 3
      F/T PSA levels measured for 3 or greater years (mean 3.5, median 3.5, range 3 to
      5.3). Of these men 22 subsequently were diagnosed with prostate cancer. We
      calculated the F/T PSA slope as the last F/T PSA minus the first F/T PSA divided
      by the interval between the measurements. The F/T PSA slopes of the patients with
      and without cancer were compared using chi-square analysis. RESULTS: Mean F/T PSA
      slope for the patients with cancer was -0.06 (median -0.03, range -0.63 to 0.22)
      compared to mean slope of -0.02 (median -0.01, range -0.57 to 0.69) for patients
      without cancer (p = 0.21). Of the patients with cancer 61% had a negative slope
      compared with 54% of patients without cancer (p = 0.59). The positive predictive
      value of a negative F/T PSA slope for subsequent cancer detection to date is only
      4%. CONCLUSIONS: A decreasing F/T PSA during a 3 to 5-year interval has little
      value in predicting subsequent diagnosis of prostate cancer. Further followup of
      a larger number of patients will be required to determine the value of
      longitudinal F/T PSA measurements in early prostate cancer detection.

PMID- 14713782
TI  - Interobserver reproducibility of percent Gleason grade 4/5 in prostate biopsies.
AB  - PURPOSE: Percent Gleason grade 4/5 (GG4/5) has been proposed as a predictor of
      prognosis in prostate cancer and it has been shown to add prognostic information
      to that given by Gleason score (GS). We recently noted that the interobserver
      reproducibility of percent GG4/5 in total prostatectomy specimens is at least as
      good as that of the GS. However, to our knowledge the reproducibility of percent
      GG4/5 in needle biopsies has not yet been investigated. MATERIALS AND METHODS: A
      consecutive series of needle biopsies from 69 men with prostate cancer was
      reviewed. Biopsies were taken according to a standardized octant protocol. All
      279 slides containing cancer were circulated among 4 genitourinary pathologists,
      who assessed GS and percent GG4/5. Results were compared pairwise and weighted
      kappa was calculated. RESULTS: The 4 observers had a mean weighted kappa for GS
      and percent GG4/5 of 0.48 to 0.55 (overall mean 0.51) and 0.52 to 0.68 (overall
      mean 0.60), respectively. There was less disagreement in percent GG4/5 when a
      single biopsy was positive for cancer than when 6 or more biopsies were positive.
      The number of positive biopsies showed a stronger correlation with a discrepancy
      in percent GG4/5 than cancer length. Disagreement was worse when cribriform or
      fusion patterns were present. CONCLUSIONS: Interobserver reproducibility of
      percent GG4/5 on prostate biopsies is at least as good as that of GS. Hence,
      concern about interobserver variability should not deter pathologists from using
      percent GG4/5. Grading appears to be most difficult when cancer is present in
      multiple biopsies or it contains cribriform or fusion patterns.

PMID- 14713783
TI  - Palliative transurethral prostate resection for bladder outlet obstruction in
      patients with locally advanced prostate cancer.
AB  - PURPOSE: The outcome of patients with advanced prostate cancer undergoing
      palliative transurethral resection of the prostate (TURP) is not well defined in
      the literature. We determined the preoperative characteristics, operative
      morbidity and postoperative outcomes of patients with advanced prostate cancer
      undergoing palliative TURP and compared these outcomes to those of patients
      undergoing TURP for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A
      retrospective review of all patients with prostate cancer undergoing palliative
      TURP at a single institution between 1994 and 2001 was performed. Operative
      reports, and outpatient and inpatient records were reviewed. Serum prostate
      specific antigen, and cancer grade and stage at cancer diagnosis were compared
      with findings at TURP. Operative statistics, postoperative outcomes and
      complication rates were compared between the palliative prostate cancer TURP
      group and a large cohort of 520 patients undergoing TURP at our institution for
      BPH during the same period. The Fisher exact and 1-sample t test were used to
      determine statistical differences in outcomes between these 2 groups. RESULTS: A
      total of 24 palliative TURPs were performed in 19 patients. At prostate cancer
      diagnosis mean patient age was 68.7 years (range 49 to 87) and median prostate
      specific antigen +/- SD was 39.7 +/- 78.3 ng/ml (range 1.5 to 334). Radiation
      therapy was the initial treatment in 11 patients (58%) and the remainder received
      initial hormonal therapy. Mean age at TURP was 74.2 years (range 50 to 91) with
      an average time from prostate cancer diagnosis to TURP of 49.7 months (range 1 to
      196). While only 22.7% of the patients had high grade cancer (Gleason score 8 to
      10) at cancer diagnosis 67% were determined to be high grade at palliative TURP
      (p = 0.001). After TURP the mean urinary flow rate decreased from 9.6 to 7.3 cc
      per second (p = 0.453) and the International Prostate Symptom Score improved from
      21.1 to 11 (p = 0.002). Compared with patients undergoing TURP for BPH those
      treated with palliative TURP were more likely to have failure of the initial
      voiding trial (p <0.001), and require reoperation (p <0.001), chronic drainage (p
      = 0.001) and re-catheterization for bleeding or obstruction (p = 0.056).
      CONCLUSIONS: Palliative TURP can be performed safely in patients with advanced
      prostate cancer with significant improvement in urinary symptoms. However, the
      rates of postoperative urinary retention and reoperation are higher than in
      patients undergoing TURP for BPH.

PMID- 14713784
TI  - Evaluation of microwave thermotherapy with histopathology, magnetic resonance
      imaging and temperature mapping.
AB  - PURPOSE: Interstitial temperature mapping was used to determine the heat field
      within the prostate by the Coretherm (ProstaLund, Lund, Sweden) transurethral
      microwave thermotherapy device. Gadolinium enhanced magnetic resonance imaging
      (MRI) and histopathology were used to determine the extent and pattern of
      coagulation necrosis following treatment. The cell kill assessment feature of the
      device was compared with MRI and histopathology. MATERIALS AND METHODS: A total
      of 12 patients were treated, including 5 with adenocarcinoma of the prostate and
      7 with benign prostatic hyperplasia. Temperature sensors were inserted from the
      perineum to map the temperature distribution. The 5 patients with adenocarcinoma
      underwent prostatectomy and subsequent histopathology 3 to 6 weeks after
      treatment. MRI and cell kill calculations were performed in all patients.
      RESULTS: Therapeutic temperatures were found in a bowl-like shape with a wide
      circumference of highest temperatures at the base of the prostate, and decreasing
      temperature and circumference toward the apex. Tissue necrosis assessed by
      histopathology, MRI and cell kill calculations overlapped reasonably well in
      shape and size. Histopathology showed that the prostatic urethra was destroyed by
      treatment. CONCLUSIONS: Coretherm microwave treatment causes significant tissue
      necrosis of the prostate, bladder neck and urethral mucosa. The cell kill
      calculation provides an on-line estimate of the amount of necrosis caused during
      treatment.

PMID- 14713785
TI  - Alternative antiandrogens to treat prostate cancer relapse after initial hormone
      therapy.
AB  - PURPOSE: We studied the efficiency of second or third line hormonal therapy for
      prostate cancer relapse after hormone therapy. MATERIALS AND METHODS: The study
      included 70 patients with advanced prostate cancer treated with hormonal therapy,
      androgen deprivation monotherapy or maximum androgen blockade including surgical
      or medical castration combined with steroidal antiandrogen, 100 mg chlormadinone
      acetate daily or nonsteroidal antiandrogens, 375 mg flutamide (FLT) daily or 80
      mg bicalutamide (BCL) daily. When the disease relapsed, we discontinued the
      antiandrogen and evaluated the patient for the antiandrogen withdrawal syndrome
      (AWS). Thereafter we administrated an alternative antiandrogen and evaluated its
      effect. RESULTS: The incidence of the AWS after first, second and third line
      hormonal therapy was 35.8%, 8.0% and 0%, respectively. The efficiency of
      subsequent hormonal therapy was not related to the occurrence of the AWS.
      Nonsteroidal antiandrogens as alternative therapies for disease relapse from
      primary therapy were effective in second line (FLT 38.1%, BCL 44.4%) or in third
      line (FLT 30.0%, BCL 28.6%) hormonal therapy. Of 5 (80%) patients who responded
      to second line therapy 4 (80%) had effective third line therapy, while only 1 of
      12 (8.3%) second line nonresponders had effective third line therapy (p = 0.003).
      The survival of second line responders was significantly better than that of
      nonresponders (5-year survival rate 92.3% vs 23.9%, p <0.001), indicating a
      potential predictive value for second line responsiveness. No significant
      clinical factor identified second line responsiveness. CONCLUSIONS: Subsequent
      nonsteroidal antiandrogen therapies were effective against prostate cancer
      relapse after hormonal therapy. The response to third line therapy was more
      effective and survival was improved from the time of first line therapy relapse
      among second line responders than that in nonresponders. Our data support the
      notion that second line responders are androgen independent but still hormonally
      sensitive.

PMID- 14713786
TI  - Direct gastrointestinal toxicity of flutamide: comparison of irradiated and
      nonirradiated cases.
AB  - PURPOSE: Gastrointestinal (GI) side effects of flutamide in cases treated for
      advanced prostate cancer are well documented. Proposed mechanisms for these side
      effects include increased serum blood levels, direct vehicle effects and/or local
      toxicity. If local toxicity, the focus of this study, mediates GI side effects of
      flutamide then cases exposed to external beam radiation (XRT) should have more
      symptoms. We hypothesize that GI side effects of flutamide are not a direct local
      toxic effect resulting in a similar side effect profile for irradiated and
      nonirradiated cases. Thus, the present study compares GI effects of flutamide in
      irradiated and nonirradiated cases. MATERIALS AND METHODS: We identified 106 of
      440 cases from a prior flutamide dose comparison study as having undergone XRT
      (56 cases) or radical prostatectomy (50 patients). The prevalence of GI side
      effects (abdominal pain/distention, diarrhea, constipation, nausea/vomiting and
      anorexia) was tallied for each treatment group and/or dosing regimen, 250 mg
      every 8 hours or 500 mg daily. Chi-square analysis with Yates' correction was
      performed for statistical analysis. RESULTS: The overall prevalence in 106 cases
      of GI side effects with flutamide was 22%. Treatment specific differences
      revealed no differences between the XRT and radical prostatectomy groups at 21%
      and 22%, respectively. Furthermore, independent analysis of treatment groups for
      each distinct side effect and dosing regimen did not identify significant
      differences. CONCLUSIONS: Irradiated cases are not at greater risk for the
      development of GI side effects from flutamide, suggesting that drug induced local
      toxicity does not mediate GI distress.

PMID- 14713787
TI  - Impact of volume weighted mean nuclear volume on outcomes following salvage
      radiation therapy after radical prostatectomy.
AB  - PURPOSE: Although salvage radiation therapy (RT) is a potentially curative
      treatment option for men with biochemical failure after radical prostatectomy
      (RP), to our knowledge there are no definitive pretreatment factors predicting
      patients likely to benefit from this treatment. We examined the impact of volume
      weighted mean nuclear volume (MNV) of biopsy specimens on disease outcomes and
      describe its usefulness as a new independent predictor. MATERIALS AND METHODS: We
      analyzed 33 patients who received salvage RT for biochemical failure after RP,
      including 11 who had received neoadjuvant hormone therapy before RP. Salvage RT
      was delivered to the prostatic bed at a total dose of 60 Gy with a 4-field
      contoured technique. Unbiased estimates of MNV were calculated from more than 100
      cancer nuclei per patient captured from biopsy specimens based on a stereological
      method and compared with other clinical and pathological findings, including
      patient age, pretreatment prostate specific antigen (PSA), PSA density, biopsy
      Gleason score, neoadjuvant therapy, surgical Gleason score, pathological stage,
      tumor volume, surgical margin status, biochemical disease-free duration before
      RT, nadir PSA and PSA doubling time before RT, and pre-RT PSA with regard to
      predicting the disease outcome after salvage RT. RESULTS: The median followup
      after salvage RT was 43.4 months. A total of 17 patients (52%) experienced
      biochemical failure a median of 6.7 months (range 0 to 48.1) after RT. On
      univariate analysis MNV and log(pre-RT PSA) were significant predictors of
      disease outcome in all patients and in the 22 nonneoadjuvant patient subset (p =
      0.0124 and 0.0159, respectively). Log(nadir PSA) and PSA doubling time were also
      significant in the latter subset (p = 0.0287 and 0.0475, respectively). However,
      dual multivariate analysis revealed that MNV was the only independent predictor
      in the 2 groups (logistic regression analysis p = 0.00931 and 0.03511, and Cox
      proportional hazards analysis p = 0.00483 and 0.02277, respectively). There was a
      statistically significant biochemical disease-free survival advantage for small
      vs large MNV in each data set (p = 0.0072 and 0.0036, respectively). CONCLUSIONS:
      Our results suggest that an estimate of MNV contributes significantly to the
      prediction of biochemical control after salvage RT. However, further
      investigation in a larger nonneoadjuvant population is needed to confirm its
      significance in combination with other clinical and pathological findings.

PMID- 14713788
TI  - Is year of radical prostatectomy a predictor of outcome in prostate cancer?
AB  - PURPOSE: We examined whether the year in which radical prostatectomy (RP) was
      performed is a predictor of treatment outcome after controlling for standard
      prognostic factors. MATERIALS AND METHODS: We examined the association between RP
      year and outcome in 6,556 patients from 7 centers using preoperative and
      pathological features. Patients underwent surgery between 1985 and 2000. The
      variables analyzed were RP year, clinical stage, pretreatment prostate specific
      antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of
      extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant
      hormones and adjuvant therapy. Median followup was 23 months (maximum 166).
      Separate Cox multivariate regression analyses were performed to analyze
      preoperative and postoperative factors. RESULTS: RP year was a predictor of
      outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p
      = 0.130). Patient outcome steadily improved with surgery through the mid 1990s
      and then it appeared to level off. CONCLUSIONS: When controlling for preoperative
      features, the year in which RP was performed is a predictor of outcome on
      multivariate analysis. This effect could not be explained by stage migration.

PMID- 14713789
TI  - Which conditions contributing to the Charlson score predict survival after
      radical prostatectomy?
AB  - PURPOSE: The Charlson score is likely to be the most frequently used comorbidity
      measure in prostate cancer. However, to our knowledge the individual prognostic
      significance of contributing conditions has not been previously studied in a
      radical prostatectomy sample. MATERIALS AND METHODS: A total of 444 consecutive
      patients were entered into this study. The 19 conditions contributing to the
      Charlson score were obtained from the preoperative cardiopulmonary risk
      assessment and the hospital discharge document. Mantel-Haenszel hazard ratios
      were estimated for comorbid (noncancer) and overall survival. Thereafter, the
      Charlson score was refined by excluding conditions with low predictive value.
      RESULTS: Mean followup was 5.9 years. Only 3 single conditions (congestive heart
      failure, peripheral vascular disease and severe renal disease) were significantly
      associated with excess overall mortality. Concerning comorbid mortality, in
      addition to these 3 diseases, chronic pulmonary disease was associated with
      increased risk. Refinement of the Charlson score improved the circumscription of
      patients at risk for premature death after radical prostatectomy. CONCLUSIONS:
      This study suggests that restricting the Charlson score to some clinically
      meaningful diseases may increase its usefulness in candidates for radical
      prostatectomy. The conventional Charlson score did not add clinically meaningful
      information supplementary to congestive heart failure, which is the most
      important single contributing condition.

PMID- 14713790
TI  - Do concerns about more advanced pathological features increase the likelihood of
      neurovascular bundle resection in black men undergoing radical prostatectomy?
AB  - PURPOSE: Traditionally black men undergoing radical prostatectomy have presented
      with higher serum prostate specific antigen (PSA) levels, Gleason grade and
      pathological stage compared to white men. We evaluated men undergoing radical
      prostatectomy at our institutions to determine if race was an independent
      predictor of neurovascular bundle resection and if racial differences existed
      with regard to clinical and pathological outcomes in men undergoing a nerve
      sparing procedure. MATERIALS AND METHODS: Between July 1995 and March 2000, 316
      men underwent radical retropubic prostatectomy for clinically localized prostate
      cancer. Patient data were gathered prospectively and reviewed with regard to age,
      race, preoperative serum PSA, operative procedure, pathological findings and
      patient followup. Racial differences were analyzed by the chi-square test or
      student's t statistic. Predictors of neurovascular bundle resection were
      evaluated using multiple logistic regression. RESULTS: Of the 316 men who
      underwent a radical retropubic prostatectomy, 126 were black and 190 were white.
      Overall, a nerve sparing procedure was performed in 77 (40.5%) white men and 44
      (34.9%) black men. When evaluating only potent men preoperatively, a nerve
      sparing prostatectomy was performed in 69.3% of white men and 58.6% of black men.
      There was no statistically significant racial difference with regard to the
      proportions of men undergoing a nerve sparing procedure. Predictors of
      neurovascular bundle resection during radical prostatectomy were preoperative
      erectile function, serum PSA level before prostate biopsy, biopsy Gleason score
      and number of cores positive for cancer. In men undergoing a nerve sparing
      radical prostatectomy there were no significant racial differences with regard to
      age, preoperative serum PSA, Gleason score, pathological stage, postoperative
      potency, continence or disease-free survival (mean followup 44 months).
      CONCLUSIONS: At our institutions a similar proportion of black and white men
      undergo nerve sparing radical prostatectomy, which appears to produce similar
      clinical outcomes in black and white men.

PMID- 14713791
TI  - Predicting quality of life after radical prostatectomy: results from CaPSURE.
AB  - PURPOSE: We investigated the usefulness of patient and tumor characteristics in
      predicting continence, potency, and physical and mental health 1 year after
      radical prostatectomy. MATERIALS AND METHODS: We studied 372 men drawn from
      Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a
      national, longitudinal cohort, who underwent radical prostatectomy alone for
      localized prostate cancer. Health related quality of life (HRQOL) was assessed
      before and 12 months after (range 9 to 15) surgery with the Physical and Mental
      Component Summaries of the RAND 36-Item Health Survey and the Sexual and Urinary
      Function scales of the UCLA Prostate Cancer Index. Covariates included clinical T
      stage, prostate specific antigen Gleason sum, age, race, income, education,
      relationship status, comorbidity and overall health self-rating. Chi-square and
      backward stepwise multivariate analysis identified differences between men who
      did and did not return to baseline HRQOL postoperatively. Return to baseline
      HRQOL score was set at 90% or greater for physical and mental health, 80% for
      continence and 75% for potency. RESULTS: After 1 year 63%, 20%, 80% and 86%
      returned to baseline continence, potency, physical health and mental health,
      respectively. Men younger than 65 years were more likely to return to baseline
      continence, potency, and physical but not mental health. Univariate analyses also
      revealed several other characteristics to predict (p <0.05) better outcomes
      including household income greater than 30,000 US dollars (potency, physical
      health), fewer comorbidities (potency, physical health), and excellent or very
      good health self-rating (mental health). In multivariate analyses subjects
      younger than 65 years were more likely to return to baseline urinary (OR 1.8, p
      <0.01), sexual (OR 2.5, p <0.01) and physical health (OR 1.8, p = 0.03).
      Furthermore, subjects with no comorbidities were more likely to return to
      baseline physical health (OR 2.5, p = 0.01), while those with an excellent or
      very good baseline health self-rating were more likely to return to baseline
      mental health (OR 2.3, p = 0.01). Clinical T stage, prostate specific antigen and
      Gleason sum did not predict return to baseline HRQOL. CONCLUSIONS: Younger
      patient age (less than 65) is associated with a greater likelihood of returning
      to baseline continence, potency and physical health after radical prostatectomy.
      In addition, patients who underwent radical prostatectomy without comorbidities
      and those with high health self-ratings are more likely to return to baseline
      physical and mental health, respectively. Preoperative tumor characteristics do
      not appear to be associated with regaining baseline HRQOL, suggesting that
      factors not measured in this model may be important in optimizing quality of life
      after radical prostatectomy.

PMID- 14713792
TI  - Feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy for
      patients with high risk or locally advanced prostate cancer: results of a phase
      I/II study.
AB  - PURPOSE: We determined the feasibility of radical prostatectomy after neoadjuvant
      chemohormonal therapy in locally advanced (stage T3 or greater) and/or high risk
      tumors (Gleason 8 to 10 and/or serum prostate specific antigen (PSA) greater than
      20 ng/ml). MATERIALS AND METHODS: Enrollment criteria included clinical stage T1
      to 2 with any Gleason grade and PSA greater than 20 ng/ml, clinical stage T3 to 4
      with any serum PSA or Gleason grade, or any clinical stage with biopsy Gleason
      grade of 8 to 10 and any serum PSA. All patients received neoadjuvant hormonal
      therapy during chemotherapy (4 cycles of paclitaxel and carboplatin and
      estramustine) followed by radical prostatectomy. Nerve sparing was decided on an
      individual basis and a nerve graft was offered to those who underwent unilateral
      or bilateral nerve resection. Perioperative morbidity, mortality and delayed
      complications were assessed. RESULTS: A total of 36 patients were enrolled. After
      chemohormonal therapy clinical stage was less in 39% of patients and greater in
      36%. Bilateral nerve sparing was performed in 3 patients and the remaining 33
      underwent either unilateral or bilateral neurovascular bundle resection with
      nerve grafts performed in 17 (52%). Deep vein thrombosis (22%) was the most
      frequent complication of chemotherapy. Minor postoperative complications occurred
      in 6 patients. At a median followup of 29 months (range 5 to 51) after radical
      prostatectomy 32 (89%) were continent and 5 (15%) preoperatively potent men
      remained potent. The positive surgical margin rate was 22%. Of all subjects 45%
      remain free from biochemical recurrence. CONCLUSIONS: Neoadjuvant chemohormonal
      therapy followed by radical prostatectomy can be performed with low morbidity.
      Positive surgical margin rates are low. This approach yielded good local control
      of disease, however impact on tumor recurrence and survival is not known.

PMID- 14713793
TI  - Transperitoneal or extraperitoneal approach for laparoscopic radical
      prostatectomy: a false debate over a real challenge.
AB  - PURPOSE: With our extensive experience of transperitoneal laparoscopic
      prostatectomy, we evaluated the advantages and disadvantages of the
      extraperitoneal approach by comparing 2 consecutive series of each procedure.
      MATERIALS AND METHODS: We reviewed 200 consecutive procedures performed by 2
      surgeons. A total of 100 transperitoneal procedures (designated group 1) were
      compared to the first 100 extraperitoneal cases (designated group 2). RESULTS:
      Mean operating time was 173 minutes in group 1 and shorter in group 2 at 163
      minutes (p = 0.003). Mean blood loss (360 ml in group 1,375 ml in group 2) and
      transfusion rates (4% in group 1, 3% in group 2) were equivalent. There were no
      major complications. Minor complications were 10% in group 1 and 9% in group 2.
      There was no statistical difference in positive margin rate between groups 1 and
      2. CONCLUSIONS: The 2 procedures are equivalent in terms of operative,
      postoperative and pathological data. Each surgeon has to choose considering
      personal experience, training and standardization.

PMID- 14713794
TI  - Balancing cure and quality of life after radical prostatectomy.

PMID- 14713795
TI  - A new technique for treating forgotten indwelling ureteral stents: silk loop
      assisted ureterorenoscopic lithotripsy.
AB  - PURPOSE: Treating forgotten indwelling ureteral stents is difficult because
      forgotten stents become encrusted and fragmented. Therefore, we developed a silk
      loop with which to loop the lower end of a forgotten ureteral stent during
      ureterorenoscopy to supply a counterforce, which fixed the stent while separating
      encrusted stones from the forgotten stent. We evaluated the success of the silk
      loop method. MATERIALS AND METHODS: Nine patients were enrolled in this study
      from 1997 to 2003. Each patient had a forgotten ureteral stent with renal stones
      on the tip of the proximal end. All consented to the procedure of silk loop
      assisted ureterorenoscopic lithotripsy (URSL) with a Lithoclast (Microvasive,
      Natick, Massachusetts) lithotriptor. RESULTS: We successfully removed the
      forgotten indwelling stent from all 9 patients with the silk loop assisted URSL
      method. CONCLUSIONS: Silk loop assisted URSL makes the removal of forgotten
      stents easier. While percutaneous nephrostolithotomy and open surgery produce
      successful results, the silk loop method is less invasive and expensive, and it
      minimizes hospital recovery time.

PMID- 14713796
TI  - Straddle injuries to the bulbar urethra: management and outcomes in 78 patients.
AB  - PURPOSE: We describe our experience with blunt straddle injuries to the anterior
      urethra and identify factors that may affect patient outcome. MATERIALS AND
      METHODS: We reviewed the San Francisco General Hospital Urologic Trauma data base
      to identify men with blunt straddle injury. We analyzed presentation and initial
      management, location and length of urethral stricture, surgical options, and long
      term outcome after reconstruction. RESULTS: Of 78 patients, 40% presented to the
      emergency department acutely and 60% presented 6 months to 10 years after injury
      complaining of obstructive symptoms, of whom 30% reported at least 1 episode of
      urinary retention. Initial acute management was suprapubic cystostomy in 81% of
      cases and primary realignment in 19%. Urethral strictures were predominantly
      located in the proximal bulb. Mean stricture length was significantly longer in
      men with delayed presentation (2.7 vs 1.8 cm, p <0.05). No relationship was found
      between stricture length and the mechanism of injury or initial management
      technique. However, patients who had undergone primary realignment required
      complex flap or graft urethroplasty at a greater rate compared with men who had
      undergone suprapubic diversion (p = 0.054). Transperineal urethroplasty was
      required in 92% of patients with the majority undergoing end-to-end anastomosis.
      The success rate was 95% at a mean followup of 25 months (range 10 to 180).
      Recurrent stricture occurred in 4 men with prior urethral manipulation and it was
      managed successfully by direct vision internal urethrotomy alone. CONCLUSIONS:
      After blunt straddle injury to the perineum the primary morbidity is anterior
      urethral stricture, for which suprapubic cystostomy is appropriate initial
      management. The majority of patients require surgery but with careful
      preoperative planning and adequate resection of fibrotic tissue the long-term
      success rate can approach 95%. If it arises, recurrent stricture responds well to
      direct vision internal urethrotomy alone.

PMID- 14713797
TI  - Ventral onlay buccal mucosal grafts for anterior urethral strictures: long-term
      followup.
AB  - PURPOSE: We present our long-term experience with buccal mucosal grafts, placed
      ventrally, for the treatment of anterior urethral strictures. MATERIALS AND
      METHODS: A total of 23 patients with anterior urethral strictures underwent
      urethral reconstruction using buccal mucosa as a ventral onlay graft, with 18
      grafts placed in the bulbar and 5 in the penile urethra. All operations were
      performed in 1 stage by a single surgeon (NAA). Mean graft length was 4.9 cm
      (range 3 to 12). International Prostate Symptom Score and uroflowmetry were
      obtained preoperatively, at 3, 6 and 12 months postoperatively, and annually
      thereafter. Urethral imaging was obtained preoperatively, at catheter removal and
      selectively thereafter. RESULTS: Patients were followed for a mean of 50 months
      (range 17 to 94). Etiology of the strictures was instrumentation (in 9),
      idiopathic (in 9), prior hypospadias repair (in 2), urethritis (in 2) and trauma
      (in 1). Of the 23 patients 21 (91%) were previously treated for urethral
      stricture with a total of 59 procedures (mean 2.8 procedures per patient).
      Success, defined as normal voiding without any need for subsequent urethral
      manipulation, was achieved in 20 of 23 patients (87%). A distal anastomotic
      stricture developed in the remaining 3 patients, each managed with 1 internal
      urethrotomy. One of these patients continues to require monthly self-dilations.
      There were no fistulas or clinically perceptible graft sacculations. CONCLUSIONS:
      With long-term followup our series confirms the durability of ventrally placed
      buccal mucosal grafts for the treatment of anterior urethral strictures. This
      proven procedure results in a high success rate with few complications.

PMID- 14713798
TI  - Local anesthesia before transrectal ultrasound guided prostate biopsy: comparison
      of 2 methods in a prospective, randomized clinical trial.
AB  - PURPOSE: We compared the analgesic efficacy of the rectal administration of
      lidocaine gel and lidocaine periprostatic infiltration prior to transrectal
      ultrasound guided prostatic biopsies. MATERIALS AND METHODS: A total of 328
      consecutive men undergoing biopsy were entered into this study. The 166 patients
      randomized to group 1 received 15 cc 2% lidocaine gel administered intrarectally
      10 minutes before prostate biopsy and the 162 in group 2 received 10 cc 1%
      lidocaine under ultrasound guidance as 2 periprostatic injections of 5 cc 5
      minutes prior to biopsy. A self-administered visual analogue scale (VAS) was used
      to assess the pain score during anesthesia (VAS 1), during biopsy (VAS 2) and 30
      minutes later (VAS 3). RESULTS: The patients in group 1 experienced statistically
      less pain than those in group 2 for mean VAS 1 (0.1 vs 1.4, p <0.0001) and mean
      VAS 3 (0.8 vs 1.4, p <0.001) but no statistically significant difference was
      noted for mean VAS 2 (2.0 vs 2.6, p = 0.04). No major morbidity was reported with
      either anesthesia. CONCLUSIONS: We are quite convinced of the necessity of local
      anesthesia to decrease pain during transrectal prostate ultrasound guided biopsy.
      Rectal administration of lidocaine gel is safe, simple and effective even when no
      difference regarding pain is noted vs lidocaine periprostatic infiltration during
      the biopsy procedure.

PMID- 14713799
TI  - Once daily, extended release ciprofloxacin for complicated urinary tract
      infections and acute uncomplicated pyelonephritis.
AB  - PURPOSE: We assessed the efficacy and safety of 1,000 mg extended release
      ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice
      daily, each for 7 to 14 days, in patients with a complicated urinary tract
      infection (cUTI) or acute uncomplicated pyelonephritis (AUP). MATERIALS AND
      METHODS: In this prospective, randomized, double-blind, North American
      multicenter clinical trial adults were stratified based on clinical presentation
      of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin
      twice daily. Efficacy valid patients had positive pretherapy urine cultures (105
      or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and
      clinical outcomes were assessed at the test of cure visit (5 to 11 days after
      therapy) and the late followup visit (28 to 42 days after therapy). RESULTS: The
      intent to treat population comprised 1,035 patients (extended release
      ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid
      (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined)
      bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85%
      (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205)
      vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily
      ciprofloxacin. Late followup outcomes were consistent with test of cure findings.
      Eradication rates for Escherichia coli, which accounted for 58% of pathogens,
      were 97% or greater per group. Drug related adverse event rates were similar for
      extended release and twice daily ciprofloxacin (13% and 14%, respectively).
      CONCLUSIONS: Extended release ciprofloxacin at a dose of 1,000 mg once daily was
      as safe and effective as conventional treatment with 500 mg ciprofloxacin twice
      daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides
      a convenient, once daily, empirical treatment option.

PMID- 14713800
TI  - Extracorporeal shock wave therapy for Peyronie's disease: exploratory meta
      analysis of clinical trials.
AB  - PURPOSE: Extracorporeal shock wave therapy (ESWT) for the treatment of Peyronie's
      disease is still controversial. This exploratory meta-analysis of published
      studies in the international literature investigates its therapeutic effects.
      MATERIALS AND METHODS: The treatment outcomes from 17 study groups identified by
      a computerized literature search were compared with natural history outcomes and
      data from control groups from 2 controlled ESWT studies. An exploratory meta
      analysis was performed because a methodologically sound meta-analysis lege artis
      did not appear appropriate, since treated groups differ considerably in
      structure, the selection of outcome measures is inconsistent and measurement is
      not standardized. RESULTS: ESWT seems to have an effect on penile pain during
      erection and on the improvement of sexual function. Pain seems to resolve faster
      after ESWT than during the course of the natural history. The effect on plaque
      size and penile curvature is less impressive. CONCLUSIONS: ESWT in Peyronie's
      disease at least seems to be effective in regard to penile pain and sexual
      function compared to natural history. Deducing from these data the effect on
      plaque size and curvature remains questionable. However, ESWT is not an evidence
      based therapy at present. A controlled (preferably pairwise matched), single
      blind, multicenter study with careful, detailed documentation of disease symptoms
      before intervention and of outcomes is required to evaluate the real effect of
      ESWT.

PMID- 14713801
TI  - A population based assessment of complications following outpatient
      hydrocelectomy and spermatocelectomy.
AB  - PURPOSE: We determine the incidence of complications following outpatient scrotal
      surgery for the treatment of hydroceles and spermatoceles. MATERIALS AND METHODS:
      A retrospective study of all patients undergoing hydrocelectomy or
      spermatocelectomy between April 1, 1997 and March 31, 1999 at 1 institution was
      performed. The hospital and office charts were reviewed, and postoperative
      complications (infection, persistent swelling, chronic pain) were recorded. The
      type of preoperative antiseptic preparation (iodine based versus chlorhexidine)
      and the presence or absence of surgical drains were also recorded. RESULTS: A
      total of 161 patients were included in the study with an average age of 53.7
      years. The overall complication rate was 19.2%. Infection/scrotal abscess
      formation occurred in 9.3% of patients, persistent swelling (treatment failure)
      in 9.3% and chronic pain in 0.6%. There was no significant difference in the
      complication rate when the preoperative preparations and the presence or absence
      of surgical drains were compared. CONCLUSIONS: The most common complications
      following scrotal surgery for hydroceles and spermatoceles are persistent scrotal
      swelling, inflammation and postoperative infection. Further prospective
      investigation is required to study factors such as the use of drains,
      preoperative and/or perioperative antibiotics and the type of surgical
      preparations, which may have a role in complication rates.

PMID- 14713802
TI  - Can higher doses of oxybutynin improve efficacy in neurogenic bladder?
AB  - PURPOSE: We evaluated the efficacy and tolerability of higher dose oxybutynin
      chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord
      injury or Parkinson's disease. MATERIALS AND METHODS: The study design was a
      prospective, 12-week dose titration trial of controlled release oxybutynin (OXY
      XL). A 7-day washout period was used before initiation of the starting dose of 10
      mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a
      maximum dose of 30 mg per day guided by patient perception of efficacy versus
      side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post
      void residuals were recorded. Criteria for study admission included post-void
      residual less than 200 ml. RESULTS: Of the 39 patients enrolled in the study 22
      had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease.
      There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the
      number of voids per day was seen in greater than 50% of the subjects. At the end
      of the study statistically significant decreases in the number of voids in 24
      hours, episodes of nocturia and incontinence episodes were observed. Residual
      urine remained unchanged from 33.9 +/- 7.6 ml at baseline to 51.3 +/- 10.4 ml
      after 12 weeks at the final dose (p = 0.17). No patient experienced serious
      adverse events and none dropped out during the course of the 12-week study. At
      the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1%
      on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL. CONCLUSIONS: Aggressive
      dosing of OXY-XL is safe and effective in patients with neurogenic bladder.
      Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg
      daily or greater) were requested by 74.4% of the patients in our study. The onset
      of clinical efficacy can occur within 1 week, and doses up to 30 mg are well
      tolerated and effective in this population.

PMID- 14713803
TI  - Efficacy of antimuscarinic therapy for overactive bladder with varying degrees of
      incontinence severity.
AB  - PURPOSE: We analyze the efficacy of tolterodine extended release (ER) for
      overactive bladder in patients with severe incontinence. MATERIALS AND METHODS:
      Patients with urinary frequency (8 micturitions or greater per 24 hours), urge
      incontinence (5 episodes or greater a week) and symptoms of overactive bladder
      for 6 months or greater were randomized to treatment with 4 mg tolterodine ER
      once daily or placebo for 12 weeks. Severe incontinence was defined as 21
      episodes or greater per week at baseline. Changes in the number of incontinence
      episodes per week and micturition frequency after 12 weeks were compared between
      treatments. RESULTS: A total of 986 patients were eligible for this post-hoc
      analysis. After 12 weeks tolterodine ER produced a significant absolute median
      reduction in incontinence episodes per week compared to placebo (9.0 vs 5.0, p
      <0.0001). For patients with severe incontinence at baseline median absolute and
      percentage reductions in incontinence episodes per week were significantly
      greater with tolterodine ER than placebo (21.0 vs 9.5, p <0.0001; 67.6% vs 29.8%,
      p = 0.022). Micturition frequency decreased (p <0.02) and volume voided per
      micturition (p <0.0001) increased significantly more with tolterodine ER compared
      with placebo in these patients. For patients with nonsevere incontinence at
      baseline median reductions in incontinence episodes per week were also
      significantly greater with tolterodine ER than placebo (6.0 vs 4.0, p <0.0001;
      71.4% vs 38.5%, p = 0.026). CONCLUSIONS: Patients with more severe incontinence
      at baseline achieved greater absolute reductions in incontinence with tolterodine
      compared to those with less severe symptoms. The degree of improvement, as
      measured by percent change, was comparable across the entire range of baseline
      incontinence severity strata. Benefits of antimuscarinic therapy may be greater
      in these patients than previously reported.

PMID- 14713804
TI  - Urodynamically defined stress urinary incontinence and bladder outlet obstruction
      coexist in women.
AB  - PURPOSE: The definition and significance of female bladder outlet obstruction
      (BOO) are poorly understood. We identified patients with urodynamic evidence of
      BOO in a cohort of women with stress urinary incontinence (SUI). MATERIALS AND
      METHODS: Women with SUI were identified from a videourodynamic data base and
      pressure flow studies were reexamined. Subjects were excluded if detrusor
      pressures could not be measured. BOO was diagnosed if the maximum flow rate was
      less than 12 ml per second and detrusor pressure at maximum flow was greater than
      20 cm water or maximum detrusor pressure was greater than 20 cm water in those
      without measurable flow. Clinical and urodynamic characteristics were compared in
      the obstructed and unobstructed groups. RESULTS: Of 104 eligible subjects 19
      (18.3%) had BOO. Maximum flow rate, mean flow rate and voided volume were
      significantly less in the BOO group than in the unobstructed group (8.7 vs 13.5
      ml per second, p = 0.004, 5.9 vs 7.9 ml per second, p = 0.001 and 180 vs 272 ml,
      p = 0.008). Detrusor pressure at maximum flow, maximum detrusor pressure and post
      void residual volume were significantly greater in the BOO group than in the
      unobstructed group (28 vs 15 cm water, p <0.0001, 31 vs 19 cm water, p <0.0001
      and 71 vs 10 ml, p = 0.008). Etiologies of BOO identified in the 19 subjects
      included prior anti-incontinence or prolapse surgery in 6, neurological
      conditions in 4, cystocele in 2, dysfunctional voiding in 3 and idiopathic in 5.
      CONCLUSIONS: SUI and BOO can coexist even in the absence of common causes of
      obstruction.

PMID- 14713805
TI  - Tape related complications of the tension-free vaginal tape procedure.
AB  - PURPOSE: The tension-free vaginal tape (TVT) procedure is a recent modality for
      managing female stress urinary incontinence. While this procedure is rapidly
      gaining popularity worldwide, little has been written about its complications. We
      describe our experience with diagnosing and treating tape related complications
      following the TVT procedure. MATERIALS AND METHODS: During the last 4 years 12
      patients underwent and 1 is scheduled for additional surgery for complications
      resulting from the TVT. Another patient is only being observed. Their records
      were reviewed to retrieve data on presenting symptoms and signs, diagnostic
      tests, surgical procedures and outcomes. RESULTS: One patient had tape erosion
      into the bladder, 5 had vaginal tape erosion (concomitant urethral obstruction in
      1) and another 8 had an obstructed urethra. The more common presenting symptoms
      were persistent urethral pain, recurrent urinary tract infection, urgency, urge
      incontinence and vaginal discharge. A total of 12 patients required partial tape
      removal or tape incision, which was done transvaginally in 11. The remaining
      patient underwent cystotomy and excision of the intravesical part of an eroded
      tape. One patient is awaiting corrective surgery and 1 with asymptomatic vaginal
      erosion is only being observed. No formal urethrolysis was performed in any case.
      Mean followup after corrective surgery in 12 patients was 4.8 months (range 1 to
      30), during which 10 remained continent and all 12 were symptom-free.
      CONCLUSIONS: Urologists should be aware of the nature and symptoms of tape
      related complications associated with a TVT procedure for prompt diagnosis and
      appropriate postoperative management.

PMID- 14713806
TI  - Outcome of surgical treatment for primary malignant melanoma of the female
      urethra.
AB  - PURPOSE: We evaluate tumor characteristics, recurrence and survival following
      surgical treatment for female urethral melanoma. MATERIALS AND METHODS: A review
      of the records of all female patients with primary localized urethral melanoma
      (11, mean age 68 years) who underwent partial urethrectomy or radical extirpation
      from 1950 to 1999 was performed to determine disease specific survival and/or
      tumor characteristics correlating with survival. Clinical and pathological stage,
      tumor location, nodal status, adjuvant therapy and tumor pathological components
      including depth, width, necrosis and vascular/lymphatic invasion, were evaluated.
      Overall disease recurrence, crude and disease specific survival rates were
      calculated using the Kaplan-Meier method. RESULTS: Malignant melanoma occurred in
      the distal urethra in all 11 cases with local extension into the vagina (T3) in
      7. Mean depth of invasion was 6.1 mm and mean tumor width was 2.0 cm. No
      vascular/lymphatic invasion or tumor necrosis was seen pathologically. No patient
      had received adjuvant therapy at the time of initial surgery. There were 7
      recurrences (6 of 7 within 1 year postoperatively). Of the 7 cases of partial
      urethrectomy, urethral recurrence (1 with concurrent lung metastasis) developed
      in 5 and none had bladder recurrence. Those who underwent radical surgery had
      recurrence in the pelvis and lungs and inguinal lymph nodes. Crude and disease
      specific survival +/- standard error at 3 years was 27 +/- 15% and 38 +/- 19%,
      respectively. CONCLUSIONS: Primary female urethral melanoma is associated with a
      rapid and high local recurrence rate (60% at 1 year). Overall and cancer specific
      survival at 3 years is 27% and 38%, respectively. Local failure may in part be
      due to inadequate resection.

PMID- 14713807
TI  - Residual urine in an elderly female population: novel implications for oral
      estrogen replacement and impact on recurrent urinary tract infection.
AB  - PURPOSE: While the distribution of post-void residual urine volume (PVR) has been
      well studied in men, scant literature is available concerning PVR in women. We
      characterized any relationship between PVR and urinary tract infection (UTI). We
      also characterized other factors that could impact bladder emptying, including
      oral estrogen replacement therapy. MATERIALS AND METHODS: Inclusion criteria were
      at least 2 clinic visits and no antimicrobial prophylaxis in the last year. Women
      with a history of diabetes or cystocele were excluded. In a 17-month period 204
      women met inclusion criteria. PVR was measured by catheterized specimen. Patients
      were categorized into groups by UTI history, namely 94 of those with no UTIs in
      the last year (group 1) and 110 with 1 or more documented UTIs in the last year
      (group 2). Factors that could affect bladder emptying were tested for the impact
      on PVR. RESULTS: Mean PVR in the study group was 53.13 ml. The mean PVR in groups
      1 and 2 was 33 and 70.25 ml, respectively. The difference between these 2 groups
      was significant (p <0.0001). Estrogen status data were available on 186 patients.
      The 62 patients on estrogen replacement therapy had a mean PVR of 39.33 ml. The
      124 patients not on estrogen replacement therapy had a mean PVR of 66.67 ml. The
      difference between these 2 groups was significant (p = 0.002) and independent of
      UTI history. CONCLUSIONS: Of elderly women those with high PVR were more likely
      to have recurrent UTIs. Improved bladder function was documented in women
      receiving oral estrogen replacement therapy.

PMID- 14713808
TI  - Sildenafil preserves intracorporeal smooth muscle after radical retropubic
      prostatectomy.
AB  - PURPOSE: Early use of vasoactive agents has been shown to rehabilitate erectile
      function after nerve sparing radical retropubic prostatectomy (RRP). The loss of
      intracorporeal smooth muscle (SM) and an increase in intracorporeal fibrosis have
      been demonstrated in vasculogenic impotence and implicated in permanent post-RRP
      erectile dysfunction. We assessed the effect of sildenafil on SM content after
      RRP. MATERIALS AND METHODS: A total of 40 potent volunteers with prostate cancer
      underwent RRP and were divided into 2 treatment groups, namely 1-50 mg sildenafil
      and 2-100 mg sildenafil every other night for 6 months beginning the day of
      catheter removal. Percutaneous biopsy was performed using general anesthesia
      prior to incision for RRP. Another biopsy was performed using local anesthesia 6
      months later. Volunteers were excluded prior to the second biopsy if they
      discontinued sildenafil. Biopsies were stained for SM and connective tissue, and
      analyzed by computer in at least 15 different fields. The paired Student t test
      was used for statistical analysis. RESULTS: A total of 11 patients in group 1 and
      10 in group 2 underwent the second biopsy. In group 1 there was no statistically
      significant change in mean SM content preoperatively to postoperatively (51.52%
      and 52.67%, respectively). In group 2 there was a statistically significant
      increase in mean SM content 6 months after RRP (42.82% vs 56.85%, p <0.05).
      CONCLUSIONS: Early use of sildenafil after RRP may preserve intracorporeal SM
      content. At higher doses post-RRP sildenafil may increase SM content. The effect
      on the return of potency is not known but maintaining the pro-erectile
      ultrastructure is integral to rehabilitating post-RRP erectile function.

PMID- 14713809
TI  - Relationship between the severity of penile curvature and the presence of
      comorbidities in men with Peyronie's disease.
AB  - PURPOSE: We investigated the relationship between penile curvature severity and
      co-morbidities in men with Peyronie's disease (PD) and assessed whether the
      severity of curvature had an impact on penile vascular status and/or erectile
      function. MATERIALS AND METHODS: Based on a 10-year period 469 patients with PD
      were retrospectively evaluated in regard to age at diagnosis, type and degree of
      penile curvature, erectile dysfunction (ED) and other comorbidities, such as
      diabetes mellitus, hypertension, serum lipid abnormalities, smoking and ischemic
      heart disease. To assess penile vascular status all men with PD underwent penile
      duplex Doppler ultrasound evaluation. The severity of penile curvature was
      classified using the Kelami system, that is grade 1--curvature 30 degrees or
      less, grade 2--30 to 60 degrees and grade 3--greater than 60 degrees. RESULTS:
      Mean patient age was 54.8 +/- 4.3 years (range 18 to 79) and the mean duration of
      symptoms was 24.8 +/- 13.7 months (range 3 to 120). The most common penile
      abnormality was dorsal curvature in 47.1% of patients. The most frequently
      documented co-morbid conditions in association with PD were hypertension in 27.2%
      of cases, smoking in 25.5%, hypercholesterolemia in 18.3%, diabetes mellitus in
      17.2%, hyperlipidemia in 15.7% and a history of penile trauma in 13.2%. There was
      no relationship between the number or severity of each of these co-morbid
      conditions and the severity of the penile abnormality. In addition, there was no
      relationship between the severity of penile curvature and penile vascular status
      in patients with PD. Moreover, the prevalence of these comorbidities, except
      smoking and penile trauma history, was significantly higher in patients with PD
      and concurrent ED than in patients with PD only. CONCLUSIONS: While co-morbid
      conditions, such as hypertension, smoking, hypercholesterolemia, diabetes
      mellitus and hyperlipidemia, are commonly seen in patients with PD and may seem
      to be risk factors for PD, there was no statistical relationship between penile
      curvature severity and any of these comorbidities. Similarly there was no
      statistically significant relationship between the severity of curvature and
      penile vascular status or ED. The fact that the prevalence of associated
      comorbidities is higher in patients with PD and ED than in patients with PD only
      indicates that these comorbidities are more likely related to ED than to the
      pathogenesis of PD.

PMID- 14713810
TI  - Use of gelatin matrix thrombin tissue sealant as an effective hemostatic agent
      during laparoscopic partial nephrectomy.
AB  - PURPOSE: We describe a technique for achieving effective hemostasis during
      laparoscopic partial nephrectomy using gelatin matrix thrombin tissue sealant.
      MATERIALS AND METHODS: Between June 2002 and April 2003, 6 patients underwent
      laparoscopic partial nephrectomy using the 2-component tissue sealant. Median
      patient age was 59 years (range 28 to 71) and followup time ranged from 1 to 10
      months (median 4.3). The tumor was at least 50% exophytic on preoperative
      computerized tomography and the diameter ranged from 2 to 3 cm (median 2.5). The
      2-component tissue sealant, consisting of a gelatin matrix granula component and
      a thrombin component, was applied after resection of the tumor and before
      reperfusion of the kidney. Time until complete hemostasis was achieved,
      postoperative bleeding, estimated blood loss, warm ischemia time and length of
      surgery were recorded. RESULTS: Hemostasis was immediate in all cases after
      application of the tissue sealant for 1 to 2 minutes to the moist resection site.
      The laparoscopic applicator was used to apply the material to the renal
      parenchyma. Hemostasis was maintained when reperfusion of the kidney was
      established. Estimated blood loss ranged from 50 to 350 cc (median 200), and no
      patient required blood transfusion. Length of surgery ranged from 89 to 230
      minutes (median 189), and warm ischemia time ranged from 10 to 14 minutes (median
      13). No postoperative bleeding occurred. CONCLUSIONS: The 2-component tissue
      sealant provided immediate and durable hemostasis in laparoscopic partial
      nephrectomy. It is a safe and time sparing alternative adjunct to currently
      available means of achieving hemostasis. In a select patient population use of
      this agent may reduce warm ischemia time by circumventing the need to perform
      laparoscopic suturing.

PMID- 14713811
TI  - Application of a fixed retractor system to facilitate laparoscopic radical
      prostatectomy.
AB  - PURPOSE: We report application of a fixed retractor system for reduction of the
      steep Trendelenberg position required to achieve deep pelvic access for
      laparoscopic radical prostatectomy. MATERIALS AND METHODS: A fixed retractor
      system consisting of a flexible arm that can be locked in position and an
      expandable 5 mm laparoscopic retractor were used to gain exposure to the deep
      pelvis. We describe in detail our technique for laparoscopic radical
      prostatectomy incorporating the fixed retractor system to facilitate each step of
      the procedure. RESULTS: Application of the fixed retractor system reduced steep
      Trendelenberg position requirements for adequate pelvic exposure from 25 to 15
      degrees in our most recent 24 laparoscopic radical prostatectomies. Furthermore,
      application of the retractor system reduced the need for an experienced
      laparoscopic assistant. CONCLUSIONS: Application of the fixed retractor system
      for laparoscopic radical prostatectomy eliminated the requirement for the steep
      Trendelenberg position to achieve access to the deep pelvis. Visceral structures
      were safely and indefatigably retracted from the operative field. The technique
      also allowed the surgical assistant to assist the surgeon with local retraction
      and aspiration.

PMID- 14713812
TI  - Critical surgical techniques for radical perineal prostatectomy.
AB  - PURPOSE: Radical perineal prostatectomy was historically the surgical treatment
      of choice for localized adenocarcinoma of the prostate until the 1980s when
      radical retropubic prostatectomy began to gain popularity. Nevertheless, the
      perineal approach possesses advantages that prompt resurgence in the interest of
      this classic operation. We review the relevant anatomy and our modified technique
      of performing a successful radical perineal prostatectomy. MATERIALS AND METHODS:
      The English literature pertaining to the different surgical approaches to radical
      perineal prostatectomy was reviewed through PubMed. Attention was paid to its
      indications, anatomical significance and various surgical techniques. RESULTS:
      Studies demonstrate no difference in the incidence of positive surgical margins
      and biochemical recurrence between radical retropubic and perineal
      prostatectomies. Furthermore, the perineal approach avoids the dorsal venous
      complex and better facilitates the vesicourethral anastomosis in the face of
      minimal pain and requirement for transfusion. We use a modified Belt approach,
      aiming to yield the most optimal outcome with minimal morbidity. A meticulous
      anatomical approach is warranted if complications such as rectal injury,
      incontinence and erectile dysfunction are to be minimized. CONCLUSIONS: With
      careful preoperative evaluation, selected patients should benefit from radical
      perineal prostatectomy for the management of localized prostate cancer.
      Familiarity with this specialized technique should be an immeasurable addition to
      any armamentarium in the therapy of prostatic diseases.

PMID- 14713813
TI  - Biliary peritonitis complicating percutaneous nephrolithomy requiring
      laparoscopic cholecystectomy.

PMID- 14713814
TI  - Abdominal wall metastasis after retroperitoneoscopic assisted total
      nephroureterectomy for renal pelvic cancer.

PMID- 14713815
TI  - Angiomyolipoma of the testis.

PMID- 14713816
TI  - Asymptomatic follicular lymphoma of the prostate discovered by abnormal digital
      rectal examination.

PMID- 14713817
TI  - Testicular rupture secondary to paint ball injury.

PMID- 14713818
TI  - Traumatic retrovesical testicular dislocation.

PMID- 14713819
TI  - Isolated testicular vasculitis presenting as a tumor-like lesion.

PMID- 14713820
TI  - Incontinence from ectopic ureter: retroperitoneal laparoscopic urovascular
      exclusion of upper pole.

PMID- 14713821
TI  - Botulinum toxin type B for type A resistant bladder spasticity.

PMID- 14713822
TI  - Botulinum toxin type B injection for management of type A resistant neurogenic
      detrusor overactivity.

PMID- 14713823
TI  - Re: Experience with the Bailez technique for laparoscopic access in children.

PMID- 14713824
TI  - Re: Editorial: Laparoscopy and urologic oncology--I now pronounce you man and
      wife.

PMID- 14713825
TI  - Re: Impaired drainage on diuretic renography using half-time or pelvic excretion
      efficiency is not a sign of obstruction in children with a prenatal diagnosis of
      unilateral renal pelvic dilatation.

PMID- 14713826
TI  - Re: Histology and clinical outcomes in patients with bilateral testicular germ
      cell tumors: the Memorial Sloan-Kettering Cancer Center experience 1950 to 2001.

PMID- 14713827
TI  - Re: Should a positive surgical margin following radical prostatectomy be
      pathological stage T2 or T3? Results from the Search database.

PMID- 14713828
TI  - Re: Neoadjuvant hormone therapy before salvage radiotherapy for an increasing
      post-radical prostatectomy serum prostate specific antigen level.

PMID- 14713829
TI  - Re: Screening cystoscopy and biopsy in patients with neuropathic bladder and
      chronic suprapubic indwelling catheters: is it valid?

PMID- 14713830
TI  - Re: Microsurgical vasoepididymostomy: a prospective randomized study of 3
      intussusception techniques in rats.

PMID- 14713831
TI  - Selective approach for transperitoneal and extraperitoneal endoscopic nephrectomy
      in children.
AB  - PURPOSE: From the experience of a large combined series of transperitoneal (TP)
      and retroperitoneal (RP) endoscopic complete and partial nephroureterectomies in
      children, we present a logical selective endoscopic approach to benign renal
      pathology. MATERIALS AND METHODS: During a 5-year period 122 complete
      nephrectomies and nephroureterectomies (bilateral 2, invisible ectopic 8) and 63
      partial nephroureterectomies for duplex (52 upper, 8 lower) or singleton polar
      disease (xanthogranulomatous pyelonephritis 1, cyst 2) were performed. Of the
      partial nephrectomies, ureterectomy, bladder repair and lower moiety
      reimplantation were performed in 8. Patient age ranged from 2.7 months to 14
      years (mean 2.9 years). Preoperative weight ranged from 2.7 to 98 kg (mean 12.3).
      The position of the renal remnant, the presence or absence of a refluxing ureter
      and the need for ureterectomy were the major determining factors affecting choice
      of endoscopic approach. RESULTS: A total of 179 (96.7%) procedures were
      successfully completed endoscopically. The 6 open conversions (3.2%) occurred
      early in our experience. The operating time reflected the complexity of the
      excision and lower urinary reconstruction (lateral and posterior RP 25 to 145
      minutes [mean 92]) TP with ureterocelectomy and bladder neck repair 105 to 355
      minutes [mean 153]. Hospital stay for RP and simple TP was 1.5 days (mean 1 to 4)
      and for complicated TP 2 to 8 days (mean 3.5). CONCLUSIONS: We suggest a
      posterior retroperitoneal approach with isolated renal excision without extended
      ureterectomy. The lateral retroperitoneal approach allows complete ureterectomy
      as well as better exposure to horseshoe and pelvic kidneys and, therefore, avoids
      exposure to intraperitoneal structures. Finally, the transperitoneal approach is
      recommended when complete moiety excision with lower urinary reconstruction is
      anticipated.

PMID- 14713832
TI  - A novel approach to the laparoscopic antegrade continence enema procedure:
      intracorporeal and extracorporeal techniques.
AB  - PURPOSE: The use of laparoscopic techniques in the construction of an antegrade
      continence enema (ACE) channel is evolving as a minimally invasive procedure that
      attempts to address issues of morbidity commonly associated with the technique as
      originally described. Because of our experience with "open" ACE construction, we
      maintain that true fecal continence of the ACE channel requires more than
      dependence on the appendicocecal sphincteric mechanism. Therefore, we have
      implemented intracorporeal or extracorporeal suturing to create a reliable
      continence mechanism. MATERIALS AND METHODS: We retrospectively reviewed 6
      patients who underwent laparoscopic ACE and compared the outcome to 20
      consecutive conventional open ACE procedures. Outcome measures included operative
      time, perioperative pain control, length of hospital stay, channel leakage,
      stenosis and herniation. RESULTS: There was no significant difference in
      operative time between the laparoscopic and conventional groups. The laparoscopic
      approach was associated with decreased postoperative pain and hospital stay.
      Difference in complication rates for leakage, stenosis and herniation was
      insignificant. CONCLUSIONS: Laparoscopic ACE, performed either completely
      intracorporeally or with laparoscopic assistance as described, provides another
      option in the surgical armamentarium to create an antegrade continence enema with
      decreased postoperative morbidity.

PMID- 14713833
TI  - Malignant extrarenal rhabdoid tumor of the bladder: 9-year survival after
      chemotherapy and partial cystectomy.

PMID- 14713834
TI  - Traumatic hematuria in children can be evaluated as in adults.
AB  - PURPOSE: Controversy exists regarding whether children who present with blunt
      abdominal trauma and microhematuria should undergo renal imaging. Adult blunt
      trauma victims who present without gross hematuria, shock, or significant
      deceleration or other major associated injuries do not require renal imaging.
      This study was designed to evaluate whether the criteria for imaging the renal
      parenchyma in adult blunt trauma victims apply to the pediatric population.
      MATERIALS AND METHODS: We retrospectively reviewed 720 consecutive pediatric
      patients with suspected renal trauma to determine mechanism of injury, evaluation
      and treatment of subsequent injuries. RESULTS: Of the 720 trauma patients with
      hematuria (mean age 8 years) 334 underwent imaging, and 59 renal injuries were
      identified (grade I 32, grade II 6, grade III 8, grade IV 12, grade V 1). A total
      of 11 patients underwent exploration, resulting in 3 nephrectomies (grade IV 2,
      grade V 1). Renorrhaphy was not necessary and all other cases were managed
      conservatively. All patients with significant renal injuries experienced either
      gross hematuria, shock (systolic blood pressure less than 90 mm Hg) or a
      significant deceleration injury. CONCLUSIONS: The decision to image pediatric
      trauma cases based on the adult criteria of gross hematuria, shock and
      significant deceleration injury is appropriate. Among 720 pediatric cases of
      potential renal injury all would have been identified.

PMID- 14713835
TI  - Results of a simplified technique for buried penis repair.
AB  - PURPOSE: The buried penis can cause secondary phimosis, recurrent balanitis and
      social embarrassment. We report our results using a simplified technique for
      repair. MATERIALS AND METHODS: A retrospective chart review of 83 consecutive
      patients undergoing buried penis repair between March 1995 and March 2001 was
      performed. Indications for surgery included recurrent balanitis, secondary
      phimosis, difficulty holding the penis during voiding, spraying of the urinary
      stream, or parental or patient concern for social embarrassment. The technique
      involves fixation of the subcutaneous penile skin at the base of the degloved
      penis to Buck's fascia of the penile shaft at the 3 and 9 o'clock positions.
      RESULTS: For the 79 patients included in the study average followup was 4.4
      years. Group 1 consisted of 26 patients who underwent circumcision at the time of
      buried penis repair. Six patients had hypospadias and 13 had penoscrotal webbing
      that was repaired simultaneously. Three patients (11.5%) had recurrent buried
      penis that required a repeat procedure and 1 (3.8%) required revision of the
      circumcision only. Three patients (11.5%) with penoscrotal webbing had mild
      recurrence requiring no further treatment. Group 2 consisted of 49 patients who
      underwent revision of the circumcision at the time of buried penis repair. Seven
      patients (14.3%) had mild recurrence that did not require further treatment.
      Group 3 consisted of 4 patients who underwent liposuction at the time of buried
      penis repair. One patient experienced lymphedema of the ventral distal shaft
      skin, which required subsequent excision. CONCLUSIONS: The buried penis repair is
      a simple and effective outpatient procedure with few complications and
      recurrences. It can be used as a primary or secondary procedure and affords good
      cosmetic results.

PMID- 14713836
TI  - Videourodynamic findings in young infants with severe primary reflux.
AB  - PURPOSE: We investigated bladder function on videourodynamic studies in infants
      with severe primary vesicoureteral reflux (VUR) and analyzed the relationship
      between VUR and intravesical detrusor pressure during the micturition cycle.
      MATERIALS AND METHODS: From 1999 to 2001, 3 female and 9 male infants with a
      median age of 9 months with VUR underwent conventional filling videourodynamics
      at our institution. Four cases were diagnosed by prenatal detection and 8 were
      diagnosed after symptomatic urinary tract infections. Reflux was bilateral in 5
      cases and unilateral in 7 (grades III to V in 7, 7 and 3, respectively). Controls
      included 10 age matched infants (median age 4 months) studied with the same
      urodynamic methodology. RESULTS: Median cystometric bladder capacity expected for
      age +/- SD was 50% +/- 58% (range 20% to 240%). Bladder capacity was low (less
      than 80%) in 10 patients. Detrusor overactivity during filling was found in only
      1 patient. In all except 1 case voiding alternated with peaks of high detrusor
      pressure (median 87 +/- 25 cm water), associated with intermittent external
      sphincter contractions with normal coordinated micturition (median 36 +/- 7 cm
      water). Cystometric residual urine (30% or greater) was noted in 3 cases. In 5
      patients VUR occurred with an increase in bladder pressure, while in 7 it
      occurred during stable filling. No significant cystometric differences were found
      between patients with reflux and controls. CONCLUSIONS: Most infants with VUR had
      decreased cystometric bladder capacity and normal detrusor activity during
      filling. High voiding pressure with concomitant sphincteric overactivity
      coexisted with normal micturition. This voiding pattern might represent a
      developmental stage of normal urine control and it may have a role in the
      etiology of reflux in some infants.

PMID- 14713837
TI  - Evolution of the treatment of vesicoureteral reflux in Spain.
AB  - PURPOSE: We determined the changes in the treatment of vesicoureteral reflux
      (VUR) at children's hospitals in Spain as well as the long-term results of
      endoscopic treatment (ET) with polytetrafluoroethylene, namely with STING
      (subureteral polytetrafluoroethylene injection). MATERIALS AND METHODS: A survey
      was performed of all pediatric urology units in Spain to determine changes in the
      diagnosis and treatment of VUR in the last 10 years. Also, a conjoint study was
      made of STING case records at 5 Spanish hospitals where there is expertise in the
      technique. RESULTS: The response rate was 34 of 44 cases (78%). The most
      significant changes were the introduction of urodynamics and the progressive
      establishment of ET as a substitute for open surgery and prolonged medical
      treatment. At more than 90% of the units ET is now done with different materials
      with a cure rate of 75% after 1 injection and a low index of complications. The
      results of the STING study in 2,035 refluxing ureters showed a cure rate of about
      90% for 2 or 3 injections for grades I to IV reflux and just under 70% for grade
      V. Also, the cure rate for complex reflux was 60% and the index of complications
      was less than 1.2% with some intravesical migration. CONCLUSIONS: There have been
      many changes in the approach to VUR with an increasing use of urodynamics and ET.
      Since the long-term results of STING are reliable and no long-term complications
      have been observed, polytetrafluoroethylene appears to be the product with the
      best quality/price ratio for use in ET. However, it is being replaced.

PMID- 14713838
TI  - Angiotensin converting enzyme gene polymorphism in Asian Indian children with
      congenital uropathies.
AB  - PURPOSE: To evaluate the role of angiotensin converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism as a risk factor for progressive renal
      damage in Asian Indian children with congenital uropathies. MATERIALS AND
      METHODS: ACE I/D polymorphism was determined by polymerase chain reaction in 84
      children with congenital uropathies and 80 unrelated healthy controls. The study
      group included primary vesicoureteral reflux (29 patients), pelviureteral
      junction obstruction (21) and posterior urethral valves (34). Mean patient age
      was 69.4 +/- 4.5 months, and mean followup period was 7.2 +/- 1.5 years. Serum
      creatinine, ultrasound, voiding cystourethrogram and dimercaptosuccinic acid
      scans were done to evaluate renal function. RESULTS: The ACE I/D genotype
      distribution was similar in the 84 patients, II in 37 (44%), DI in 30 (35.7%) and
      DD in 17 (20.2%), and 80 controls, II in 36 (45%), DI in 30 (37.5%) and DD in 14
      (17.5%), chi-square 0.00, p = 1.0). Renal scarring was seen in 49 of 84 patients
      (58.3%), with D allele present in 35 of 49 (71.4%), compared to 12 of 84 patients
      (34.2%) in the nonscarring group (chi-square 4.2, p = 0.02). Progressive scarring
      and renal failure were seen in 23 (27.3%) and 26 (31%) of patients, respectively,
      with D allele present in 21 of 23 (91.3%) and 21 of 26 (81%), respectively (chi
      square 5.4, p = 0.001). Multivariate analysis showed that D allele is an
      independent risk factor for renal damage. CONCLUSIONS: The presence of D allele
      in I/D polymorphism of angiotensin converting enzyme gene is associated with
      progressive deterioration of renal function in congenital uropathies. The D
      allele was also significantly associated with renal scarring independent of known
      risk factors such as grade of reflux, age at diagnosis, gender and urinary tract
      infection.

PMID- 14713839
TI  - Decrease in maximal force generation in the neonatal mouse bladder corresponds to
      shift in myosin heavy chain isoform composition.
AB  - PURPOSE: A change in calcium handling has been proposed as the cause of decreased
      maximal force generation by neonatal bladders with growth. Recent studies suggest
      that increased myosin heavy chain isoform SM1 increases force generation. We
      studied force generation in neonatal mouse bladders to determine if decreases in
      SM1 corresponded with decreased force. MATERIALS AND METHODS: C57Bl/6 mice were
      studied from birth to 12 weeks of life (adulthood). The bladder strip contractile
      response to KCl and bethanechol was followed by the inhibition of rho-kinase
      activity by Y-27632. The mRNA levels for SM1/SM2 were determined using reverse
      transcriptase-polymerase chain reaction and protein levels were determined using
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Muscle fraction per
      cross-sectional area was determined by trichrome staining. RESULTS: Newborn
      bladders generated significantly more tension in response to KCl (43.3 vs 17.4
      mN/mm2, p = 0.02) and bethanechol (40.6 vs 11.9 mN/mm2, p = 0.05) than adult
      bladders. Inhibition of rho-kinase resulted in similar decreases in tension in
      all bladders. SM1 mRNA decreased slightly from 60% at birth to 50% at 12 weeks.
      SM1 protein decreased from 72.5% at birth to 50% by 3 weeks and it remained
      stable at 12 weeks. Total myosin per gm protein remained stable. Muscle fraction
      decreased from 63.8% at birth to 58.6% at 12 weeks (p = 0.4). CONCLUSIONS: We
      noted a decrease in SM1 that corresponded to a decrease in bladder force
      generation. The concept that SM1 contributes to the optimal assembly of myosin
      filaments suggests that changes in myosin isoforms may have a role in the
      decrease in voiding pressures seen in normal children.

PMID- 14713840
TI  - Botulinum-A toxin injection into the detrusor: a safe alternative in the
      treatment of children with myelomeningocele with detrusor hyperreflexia.
AB  - PURPOSE: We prospectively evaluated the efficacy and durability of botulinum-A
      toxin in the treatment of detrusor hyperreflexia in children with
      myelomeningocele (MMC). MATERIALS AND METHODS: This study involved 15 patients
      with MMC (10 male and 5 female, mean age 5.8 years), all nonresponders to orally
      and intravesically administered anticholinergic medication and all on clean
      intermittent catheterization. Pretreatment assessment included a videourodynamic
      evaluation, an incontinence score and a mercaptoacetyltriglycine-3 renal scan. We
      injected 10 U/kg to a maximum of 360 U of botulinum-A toxin into the detrusor at
      25 to 40 sites, sparing the trigone. Followup lasted between 12 and 30 months.
      All children underwent a urodynamic reevaluation, an assessment of the bladder
      capacity and an incontinence score at 3, 9 and 12 months after the first
      injection. A second intravesical injection was administered after 12 months and
      followup repeated as in the first year. RESULTS: After the first injection
      treatment mean bladder reflex volume increased from 72.00 +/- 28.12 ml to 298 +/-
      32.45 ml (mean +/- SD, p <0.001). Maximum detrusor pressure decreased from 78.76
      +/- 23.14 cm H2O to 42.76 +/- 24.34 cm H2O (p <0.001). Maximum bladder capacity
      increased from 136.34 +/- 45.71 ml to 297.02 +/- 87.17 ml (p <0.001). Detrusor
      compliance increased from 18.29 +/- 27.19 ml/cm H2O to 51.17 +/- 38.17 ml/cm H2O
      (p <0.001). Of the 15 patients 13 became completely dry with CIC. The remaining 2
      patients improved from score 3 to 1. Results after 9 months were similar to those
      obtained after 3 months. Mean durability of the effect of the drug was 10.5
      months after the first as well as after the second intravesical injection.
      CONCLUSIONS: Botulinum-A toxin is a safe alternative in the management of
      detrusor hyperreflexia in children with MMC. The preliminary results regarding
      urodynamic parameters and continence have been promising.

PMID- 14713841
TI  - What is the rate of spontaneous testicular descent in infants with
      cryptorchidism?
AB  - PURPOSE: It has been speculated that late spontaneous testicular descent occurs
      in more than 70% of newborns with cryptorchidism. Based on this belief, the
      decision for orchiopexy is often deferred during infancy. We reviewed our 10-year
      experience of treating infants with cryptorchidism to document the rate of
      spontaneous testicular descent. MATERIALS AND METHODS: A total of 1,235 patients
      with cryptorchidism were referred to our pediatric urology clinic between 1990
      and 2000. Of these patients 278 presented before age 12 months. The medical
      records were reviewed explicitly to document the rate of spontaneous testicular
      descent. RESULTS: Spontaneous descent occurred in only 6.9% of patients with
      cryptorchidism reexamined at age 1 year or beyond. All patients with eventual
      spontaneous descent initially presented by age 6 months. Of those initially
      presenting beyond age 6 months no patient had spontaneous testicular descent.
      CONCLUSIONS: Contrary to previous belief, spontaneous testicular descent is
      uncommon in infants with cryptorchidism and is rare beyond age 6 months.

PMID- 14713842
TI  - Persistent Mullerian duct syndrome associated with 47,XXY genotype.

PMID- 14713843
TI  - Comprehensive evaluation of ureteral healing after electrosurgical endopyelotomy
      in a porcine model: original report and review of the literature.
AB  - PURPOSE: Endopyelotomy (EP) has yet to equal the success achieved with open
      dismembered pyeloplasty. To understand better the ureteral response to EP we
      performed a timed histopathological evaluation of the porcine ureter after
      Acucise (Applied Medical, Rancho Santa Margarita, California) EP. MATERIALS AND
      METHODS: In 28 domestic pigs bilateral Acucise EPs were performed and bilateral
      7Fr stents were placed. The kidneys, ureters and bladder were harvested after EP
      at 0, 1, 2, 3, 6, 12 and 18 hours, 1, 3 and 5 days, and 1, 2, 4 and 8 weeks. The
      stents were removed after 4 weeks. The healing area of the ureter was sectioned.
      Half was fixed in formalin 10%, stained and evaluated by light microscopy. The
      other half was frozen and reverse transcriptase-polymerase chain reaction was
      performed to measure steady state levels of epidermal growth factor, transforming
      growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, keratinocyte
      growth factor, vascular endothelial growth factor, insulin-like growth factor,
      platelet derived growth factor, collagen type 1, integrin and fibronectin
      transcript expression. Immunohistochemistry for actin, desmin and myosin
      expression was completed. The same studies were applied to the mid portion of the
      unoperated ureter. RESULTS: Initial sealing of the ureterotomy defect was by
      blood clot and periureteral fat. Complete healing of the mucosa was observed at 2
      weeks in animals without an associated urinoma. However, in no case did the
      muscle layer bridge the whole circumference of the ureter despite followup out to
      8 weeks. In the operated ureter elevated expression of keratinocyte growth
      factor, vascular endothelial growth factor, TGF-alpha, TGF-beta 1, TGF-beta 3 and
      integrin was detected 2 hours after the operation and sustained for 7 to 14 days
      after the procedure. Immunohistochemistry revealed that most presumed myocytes
      seen in the defect were actually myofibroblasts. Persistent urinoma formation
      beyond the first few days appeared to slow the healing process. CONCLUSIONS:
      Urothelium regenerated rapidly over an iatrogenic ureteral defect despite the
      absence of a lamina propria. Muscle cell coverage failed to occur completely at 8
      weeks. In the initial 8 weeks of the healing process myofibroblasts appear to be
      prevalent. A persistent urinoma negatively impacts the healing process.

PMID- 14713844
TI  - Immunotherapy for urological malignancies.
AB  - PURPOSE: For decades urologists have successfully used immunotherapy in the
      battle against cancer. Interleukin-2 in renal cell carcinoma and bacillus
      Calmette-Guerin in bladder cancer are standard primary and/or adjunctive
      therapies for these diseases. Recent advances in our understanding of mechanisms
      governing immune system activation have fostered a myriad of novel
      immunotherapeutic approaches that show great promise in vivo but have had limited
      success in human trials to date. This review highlights current immunotherapy
      strategies that may prove to be successful treatments for urological cancers.
      MATERIALS AND METHODS: We performed a MEDLINE literature search for articles
      relating to immunotherapy in bladder, prostate and renal cell carcinoma in
      animals and humans. We included the most promising developments in this review.
      RESULTS: In addition to combining existing therapies to improve their efficacy,
      novel approaches that attempt to exploit the immune system ability to identify,
      target and eradicate malignancies are now being developed. These therapies
      include the use of antitumoral monoclonal and bi-specific antibodies,
      manipulation of T-lymphocyte costimulatory molecules and the administration of
      newly discovered cytokines as well as the development of antitumor vaccines.
      CONCLUSIONS: To date the full potential of immunotherapy for the treatment of
      urological malignancies has not been recognized. As our knowledge of the immune
      system expands, so too may our ability to manipulate it to affect tumor
      regression. This review describes the most recent and most promising developments
      in immunotherapy for urological malignancies.

PMID- 14713845
TI  - Renal abnormalities in rat fetuses exposed to doxorubicin.
AB  - PURPOSE: A rat model of the VATER (vertebral defects, anal atresia, tracheo
      esophageal fistula with esophageal atresia, renal defects and radial limb
      dysplasia) association was created by exposing fetuses to doxorubicin early in
      gestation. Most fetuses had an absent bladder with ureters that were grossly
      dilated. We determined the effect of this absent bladder on kidneys development,
      particularly whether dysplasia was evident. MATERIALS AND METHODS: Nine timed
      pregnant rats were injected intraperitoneally with doxorubicin at a dose of 2
      mg/kg body weight on days 6 to 9 of gestation. The control group of 3 rats
      received saline. Fetuses were recovered on day 21 and examined macroscopically.
      Quantitative measurements were taken of renal wet and dry weights, renal length
      and ureteral diameter. Serial sections were then taken and stained alternately
      with hematoxylin and eosin or trichrome. The kidneys were compared under light
      microscopy. Comparisons between control and treated groups were made with the
      Student t test. RESULTS: An absent bladder was confirmed in 50 of the 55 fetuses
      (91%). In most fetuses the kidneys were correctly located, although they were
      hydronephrotic and poorly developed. This finding was confirmed quantitatively
      with significant differences in treated and control fetuses in renal length (5.24
      vs 4.13 mm, p <<0.01) and in the ratio of wet renal weight to body weight and dry
      weight (2.7 vs 3.4 mg, p <<0.01). Dilated, tortuous ureters were found
      bilaterally in most cases. Microscopically the kidneys had abnormal architecture
      and were less mature than in controls. Nephron induction was poor with abnormal
      configurations. Tubular differentiation was decreased and the medulla was thin
      and less cellular than in controls. Dilatation occurred mainly in the collecting
      system and ducts/tubules. There was no collagen deposition/fibrosis or aberrant
      tissue. CONCLUSIONS: In this rat model the kidneys are exposed to obstruction
      early in development since the bladder does not form. The resulting kidneys are
      hydronephrotic with decreased parenchyma and poor differentiation. However, there
      is no fibrosis or aberrant tissue.

PMID- 14713846
TI  - Calcium oxalate crystal adherence in the rat bladder: restoration of anti
      adherence after acid treatment.
AB  - PURPOSE: A role for the mucous lining of the urinary tract to prevent crystal
      adherence as well as the ability of glycosaminoglycans and other substances to
      restore anti-adherence after removal of the mucous lining was studied in the rat
      bladder. MATERIALS AND METHODS: Following catheterization of the rat bladder a
      dilute solution of acid was introduced, which has been shown to remove the mucous
      lining. Sialic acid, hyaluronic acid, chondroitin sulfate, dermatan sulfate,
      heparin, pentosan polysulfate and urine were introduced into the bladder in an
      attempt to restore the anti-adherence properties removed by acid treatment.
      Radioactive calcium oxalate crystals were introduced into the bladder, followed
      by saline washes, and the crystals remaining were used as a measure of crystal
      adherence. Controls were mucous intact and acid treated bladders. RESULTS:
      Hyaluronic acid, chondroitin-6-sulfate and chondroitin-4-sulfate did not
      influence adherence. Dermatan sulfate, heparin and pentosan polysulfate restored
      anti-adherence, while sialic acid and urine promoted adherence. CONCLUSIONS: The
      mucous lining of the urinary tract serves as a defense against calcium oxalate
      crystal adherence. Dermatan sulfate decreases crystal adherence, whereas sialic
      acid promotes adherence. The balance between these 2 factors may have a role in
      stone formation.

PMID- 14713847
TI  - Down-regulation of HLA class I antigen processing molecules: an immune escape
      mechanism of renal cell carcinoma?
AB  - PURPOSE: Proper HLA class I antigen processing and presentation is a prerequisite
      for the recognition of tumor cells by cytotoxic T lymphocytes. To date there
      exist only limited information on the expression of components of the HLA class I
      associated antigen processing machinery (APM) in surgically removed benign renal
      cell adenoma, and primary and metastatic renal cell carcinoma (RCC). MATERIALS
      AND METHODS: A total of 133 primary RCCs of different subtypes, 10 renal cell
      adenoma biopsies, 32 matched metastases of different localization and autologous
      normal kidney epithelium were immunohistochemically analyzed for the expression
      of HLA class I antigens, low molecular weight protein (LMP)2 and LMP7, the
      transporter associated with antigen processing subunit (TAP1) and beta 2
      microglobulin (beta 2-m). RESULTS: Normal kidney tissue showed strong cytoplasmic
      staining intensity for LMP2, LMP7 and TAP1, whereas beta 2-m and HLA class I
      heavy chains were detected on the cell surface. A low frequency of HLA class I HC
      and beta 2-m down-regulation was found in RCC. In contrast, primary RCC and
      metastases showed a high frequency of a total lack of heterogeneous TAP1, LMP2
      and LMP7 expression, which was often coordinately regulated. APM component
      deficiencies were associated with RCC subtypes but not with tumor grading and
      staging. CONCLUSIONS: HLA class I APM component abnormalities appear to represent
      an immune escape mechanism of RCC. This finding emphasizes the need to evaluate
      the integrity and expression of these molecules in patients with RCC, especially
      in those selected for treatment with T-cell based immunotherapy.

PMID- 14713848
TI  - Hepatocyte growth factor activator inhibitor types 1 and 2 are expressed by
      tubular epithelium in kidney and down-regulated in renal cell carcinoma.
AB  - PURPOSE: Hepatocyte growth factor (HGF) and its receptor MET have been implicated
      in kidney development and renal cell carcinoma (RCC) progression. HGF is secreted
      as an inactive proform and it must be activated to initiate MET signaling. HGF
      activator (HGFA) activates pro-HGF in injured tissue. We evaluated the expression
      of HGFA and its endogenous inhibitors HAI-1 and HAI-2 in normal kidney and RCC.
      MATERIALS AND METHODS: We examined the gene expression of HGFA, HAI-1, HAI-2, HGF
      and MET in a normal kidney by laser captured microdissection, followed by reverse
      transcriptase-polymerase chain reaction. We also quantified the mRNA levels of
      these proteins in 14 RCC cases by real-time reverse transcriptase-polymerase
      chain reaction. RESULTS: HAI-1 and HAI-2 were abundant in the normal kidney. The
      uriniferous tubules showed the highest levels of HAI-1 and HAI-2 mRNA. HGFA was
      hardly detectable in the normal kidney. However, in the kidney with RCC a low but
      distinct level of HGFA mRNA became detectable in the tumor and adjacent renal
      tissue. The HAI-1 mRNA level was significantly and consistently down-regulated in
      RCC relative to normal tissue. HAI-2 mRNA was also significantly low in the
      advanced stage of RCC. MET was up-regulated in most cases of RCC. CONCLUSIONS:
      HAI-1 and HAI-2 were expressed in renal tubular epithelial cells. The expression
      of the 2 HAIs was significantly down-regulated in RCC, whereas HGFA expression
      was enhanced in the diseased kidney, suggesting an imbalance between HAI and its
      target proteinases, including HGFA, in favor of proteinase activities in RCC.

PMID- 14713849
TI  - Modulation of tumor growth and tumor induced angiogenesis after epidermal growth
      factor receptor inhibition by ZD1839 in renal cell carcinoma.
AB  - PURPOSE: ZD1839 or Iressa (AstraZeneca, Macclesfield, United Kingdom) is an
      orally active, selective epidermal growth factor receptor tyrosine kinase
      inhibitor. We evaluated the antitumor activity of ZD1839 in human renal cell
      carcinomas (RCC). MATERIALS AND METHODS: Six established human RCC lines and
      surgical specimens from 10 patients with RCC were used. Protein expression was
      detected by Western blotting and/or immunohistochemistry. The concentrations of
      vascular endothelial growth factor and interleukin-8 in the supernatants were
      measured by enzyme-linked immunosorbent assay. Cell cycle progression and the
      apoptotic ratio were evaluated by flow cytometry. In vitro angiogenesis was
      measured using human umbilical vascular endothelial cells by capillary-like
      network formation analysis. In vivo SKRC-49 cells injected subcutaneously into
      athymic nude mice were treated with various doses of ZD1839 orally. The effect of
      ZD1839 on tumor xenografts angiogenesis was evaluated by immunohistochemistry
      using CD34 Ab. RESULTS: Epidermal growth factor receptor was activated in all RCC
      lines and over expressed in 7 of 10 RCC specimens (70%) compared with adjacent
      normal renal tissues. Treatment of SKRC-49 cells with ZD1839 (0.1 to 10 microM)
      for 48 hours resulted in the accumulation of cells in the G1 phase and a 30% to
      50% decrease in cellular proliferation compared with untreated controls (p
      <0.01). The tumor xenograft study confirmed that ZD1839 (50 to 100 mg/kg daily)
      significantly inhibited SKRC-49 tumor growth compared with controls within 3
      weeks after treatment (p <0.01). Vascular endothelial growth factor and
      interleukin-8 production was significantly decreased in ZD1839 treated SKRC-49
      cells compared with untreated controls (p <0.01). Treatment of human umbilical
      vascular endothelial cells with SKRC-49 supernatants treated with ZD1839 for 11
      days resulted in an approximate 80% decrease in tubule formation compared with
      untreated controls (p <0.01). Immunohistochemical assays showed that ZD1839
      treatment resulted in a significant decrease in CD34 positive neovessels compared
      with controls in SKRC-49 xenografts. CONCLUSIONS: These results suggest that the
      antitumor activity of ZD1839 appears to derive not only from direct inhibition of
      cell proliferation, but also from the inhibition of tumor angiogenesis in RCC.

PMID- 14713850
TI  - A diagnostic test for prostate cancer from gene expression profiling data.
AB  - PURPOSE: Multiple recent studies show excellent classification accuracy using
      bioinformatics tools applied to expression profiling data on various tumors.
      However, the clinical applicability of these techniques remains unfulfilled
      because of difficulty in translating complex multigene mathematical algorithms
      into reproducible, platform independent tests. We recently developed a broadly
      applicable platform independent method based on simple ratios of gene expression
      to diagnose and predict outcome in cancer. In the current study we applied this
      technique to the diagnosis of prostate cancer. MATERIALS AND METHODS: We
      developed a ratio based predictive model using a training set of 32 samples with
      previously published gene profiling data. We then tested and refined the model
      using additional independent samples with previously published microarray data
      from another source (that is the test set of 34 samples). Finally, the optimal
      ratio based test was examined with quantitative reverse transcriptase-polymerase
      chain reaction for data acquisition in a third cohort of samples consisting of 10
      frozen normal and 10 tumor prostate tissues. RESULTS: A 3-ratio test using 4
      genes was 90% accurate (18 of 20 samples) for distinguishing normal prostate and
      prostate cancer samples obtained at surgery (Fisher's exact test p = 0.0007).
      This test did not result in any false-negative findings. CONCLUSIONS: We describe
      and validate a new gene ratio based test for the diagnosis of prostate cancer,
      which was developed from the analysis of extensive gene profiling data for the
      diagnosis of prostate cancer. This test can be easily adapted to the clinical
      arena without the need for complex computer software or hardware. We anticipate
      that the gene ratio based diagnosis of prostate cancer using fine needle
      aspirations could serve as a useful adjunct to standard histopathological
      techniques.

PMID- 14713851
TI  - Inorganic selenium retards progression of experimental hormone refractory
      prostate cancer.
AB  - PURPOSE: The development of hormone refractory prostate cancer marks the onset of
      the terminal phase of the disease. Despite the use of traditional
      chemotherapeutic drugs as well as many novel agents life expectancy is not
      significantly increased beyond palliative care alone. Selenium is a micronutrient
      that is incorporated into a number of essential enzymes and a minimum intake is
      necessary for the maintenance of health. In the last few years evidence has
      accumulated from case-control and limited randomized control data that
      supranutritional doses of selenium could inhibit the progression of prostate
      cancer. While much attention has focused on its use as a chemopreventive agent,
      its use as specific therapy has been limited. We hypothesized that dietary
      supplementation of selenium would inhibit the progression of hormone refractory
      prostate cancer in an experimental model. MATERIALS AND METHODS: We established
      orthotopic PC3 tumors in the prostates of 6-week-old male nude mice and fed them
      a baseline selenium replete diet (0.07 ppm), supplementing intake with different
      forms of selenium (sodium selenate, selenomethionine, methylselenocysteine and
      selenized yeast) at 2 different concentrations (0.3 and 3 ppm) in drinking water.
      RESULTS: Inorganic selenium (sodium selenate) significantly retarded the growth
      of primary prostatic tumors and the development of retroperitoneal lymph node
      metastases, which was associated with a decrease in angiogenesis. CONCLUSIONS:
      High dose dietary supplementation of inorganic selenium inhibits the progression
      of hormone refractory prostate cancer, which is due at least in part to a
      decrease in angiogenesis.

PMID- 14713852
TI  - Effective treatment of experimental androgen sensitive and androgen independent
      intraosseous prostate cancer with targeted cytotoxic somatostatin analogue AN
      238.
AB  - PURPOSE: The targeted cytotoxic somatostatin analogue AN-238, consisting of 2
      pyrrolinodoxorubicin (AN-201) linked to carrier octapeptide RC-121, is scheduled
      for clinical trials. To extend previous findings we tested AN-238 on human
      androgen sensitive MDA-PCa-2b prostate cancers grown subcutaneously and androgen
      independent LNCaP derived C4-2 prostate cancers xenografted into the tibiae of
      nude mice. MATERIALS AND METHODS: Changes in serum prostate specific antigen
      (PSA) levels were monitored by radioimmunoassay. Somatostatin receptors in tumor
      samples were characterized. RESULTS: Three intravenous injections of AN-238 at
      150 nmol/kg doses inhibited the growth of subcutaneous MDA-PCa-2b tumors by 62%
      vs controls (p <0.05) and were more effective than equimolar doses of the radical
      AN-201 (p <0.05). AN-238 also decreased serum PSA levels by 62% vs controls (p
      <0.01). In nude mice bearing intra-osseous implanted C4-2 prostate cancers AN-238
      decreased serum PSA levels by 65% compared with controls after 5 weeks of therapy
      (p <0.05), while AN-201 was ineffective. All AN-238 treated mice were alive at
      the termination of the experiment, while only 50% of controls and 60% of animals
      treated with AN-201 survived (p <0.01). Histological evaluation of intraosseous
      C4-2 tumors showed that AN-238 induced a significant increase in apoptosis (p
      <0.05). MDA-PCa-2b and C4-2 tumors showed high affinity binding for somatostatin
      and the expression of mRNA for somatostatin receptor subtypes 1, 2A and 5.
      CONCLUSIONS: The current study demonstrates the efficacy of the somatostatin
      analogue AN-238 for subcutaneous MDA-PCa-2b as well as for intraosseous C4-2
      prostate cancers xenografted into nude mice. This targeted cytotoxic analogue
      could represent a new therapy for patients with advanced metastatic prostate
      carcinoma.

PMID- 14713853
TI  - Expression of annexin I, II and VII proteins in androgen stimulated and recurrent
      prostate cancer.
AB  - PURPOSE: We performed a comprehensive survey of annexin I, II and VII protein
      expression in patient matched benign prostatic epithelium (BPE), androgen
      stimulated prostate cancer (AS-CaP) and recurrent prostate cancer (R-CaP).
      MATERIALS AND METHODS: Annexin I, II and VII was immunostained in 23 matched
      pairs of BPE and AS-CaP specimens, and in 25 R-CaP specimens. Protein expression
      was assessed visually and using color digital video image analysis. RESULTS: The
      expression levels of annexins I and II was decreased from BPE to AS-CaP in all
      patients examined using visual assessment (22 of 22) or digital image analysis
      (18 of 18 for annexin I and 22 of 22 for annexin II). Annexin I mean optical
      density (MOD) decreased by 69% (0.718 to 0.222, p <0.0001) and annexin II MOD
      decreased by 71% (0.820 to 0.238, p <0.0001). Annexin I MOD further decreased
      almost 50% in R-CaP compared with AS-CaP (0.117 vs 0.222, p <0.0065) and annexin
      II MOD further declined by 37% (AS-CaP 0.238 vs R-CaP 0.150, p <0.0001). Annexin
      VII MOD showed no significant change between BPE and AS-CaP (0.229 and 0.214,
      respectively) but it decreased 14% in R-CaP vs AS-CaP (0.184 vs 0.214, p
      <0.0051). CONCLUSIONS: Annexins I and II expression are decreased in AS-CaP
      compared with BPE and a further reduction is observed with progression from AS
      CaP to R-CaP. Annexin VII protein expression is decreased in R-CaP, although AS
      CaP and BPE are similar. This study suggests that the dysregulations of annexin
      proteins I, II and VII are important events in prostate carcinogenesis and
      progression.

PMID- 14713854
TI  - Effect of augmentation cystoplasty on bone metabolism in chronic uremic rats.
AB  - PURPOSE: We examined the impact of urinary diversion using several types of
      intestinal segments on the bone metabolism of growing rats with renal
      insufficiency. MATERIALS AND METHODS: A total of 110, 8-week-old Sprague-Dawley
      rats underwent 2-stage subtotal nephrectomy by removal of 5/6 of the renal mass
      or sham operation. Except for a uremic control group all uremic rats underwent
      enterocystoplasty using stomach, ileum or colon. An additional group with colic
      augmentation received the bisphosphonate ibandronate. Bone mineral density of the
      tibia and lumbar spine, serum analysis and urinary excretion of the bone
      resorption marker deoxypyridinoline were determined monthly for 12 weeks. At
      study termination bone ash weight, bone mineral analysis and serum osteotropic
      hormone levels were determined. RESULTS: All groups undergoing subtotal
      nephrectomy had a decreased endogenous creatinine clearance of approximately 30%.
      The lowest gains in tibial and lumbar spine bone mineral density were observed in
      animals undergoing ileocystoplasty. Femoral calcium content was significantly
      decreased in uremic ileocystoplasty rats compared with uremic controls. These
      changes were not induced by alterations in serum pH, nor were they associated
      with accelerated bone resorption as assessed by deoxypyridinoline. Ibandronate
      prevented changes related to bone resorption and increased bone mass.
      CONCLUSIONS: Our results suggest that cystoplasty using ileum segments can
      aggravate renal bone disease in growing rats with mild uremia. Since the acid
      base state was unchanged, other properties of the interposed ileum segment must
      be responsible for the negative effect on bone metabolism.

PMID- 14713856
TI  - No pathogenic mutations in the uroplakin III gene of 25 patients with primary
      vesicoureteral reflux.
AB  - PURPOSE: The uroplakin III (UPIII) knockout mouse provides a good model for human
      primary vesicoureteral reflux (VUR). Since to our knowledge no causative genes in
      human VUR have been identified to date, we wondered whether the UPIII gene might
      be involved in human primary VUR. Therefore, the UPIII gene was sequenced to see
      if any mutations could be detected in patients with primary VUR. MATERIALS AND
      METHODS: DNA was obtained from 25 patients who were surgically treated for
      primary VUR. Each patient had a family history positive for VUR. RESULTS: No
      pathogenic mutations were identified in patient DNA. One missense mutation
      (Ala154Pro) not reported in the human genome data base was observed. However,
      because its frequency in the patient and control populations was similar, it was
      interpreted as a polymorphism. CONCLUSIONS: Although mutations in regulatory
      elements affecting gene function cannot be excluded, the UPIII gene does not seem
      to have a major role in primary VUR in humans.

PMID- 14713855
TI  - Dietary L-arginine supplementation improves the glomerular filtration rate and
      renal blood flow after 24 hours of unilateral ureteral obstruction in rats.
AB  - PURPOSE: Unilateral ureteral obstruction (UUO) results in a significant change in
      renal blood flow (RBF) and glomerular filtration rate (GFR) by 24 hours. The
      intake of L-arginine, a substrate of nitric oxide (NO) synthase (NOS), can
      augment NO production. NO can maintain renal function through its vasodilatory
      action. Therefore, we examined the effect of dietary arginine supplementation on
      renal function in UUO. MATERIALS AND METHODS: GFR and RBF were measured by inulin
      and para-aminohippurate clearance, respectively, in control rats and in rats 24
      hours after UUO. Rats were given arginine with or without the concomitant
      administration of N-nitro-L-arginine methyl ester. Urinary nitrate/nitrite
      (NO2/NO3) was measured by the Griess reaction and urinary cyclic guanosine
      monophosphate was determined by enzyme-linked immunosorbent assay. The expression
      of renal inducible NOS was determined by immunohistochemistry. RESULTS: Urinary
      NO2/NO3 was significantly increased after 2 weeks of arginine, confirming
      increased NO production. In control rats GFR and RBF were not significantly
      different in untreated vs arginine treated groups. In contrast, arginine
      treatment significantly increased GFR in the obstructed kidney (0.06 +/- 0.01 to
      0.14 +/- 0.02 ml per minute per 100 gm) and the contralateral kidney compared
      with control UUO. RBF was also significantly increased by arginine. The increases
      in renal function with arginine were blunted by a NOS inhibitor in obstructed and
      contralateral kidneys. Inducible NOS expression was increased in obstructed and
      contralateral kidneys. CONCLUSIONS: This study demonstrates that L-arginine
      supplementation can improve renal function in acute UUO. This finding suggests
      that NO system may be a future site of pharmacological intervention for UUO.

PMID- 14713857
TI  - Diabetes mellitus increases the rate of development of decompensation in rats
      with outlet obstruction.
AB  - PURPOSE: We investigated the effects of the combination of bladder outlet
      obstruction and diabetes mellitus on in vitro rat bladder body strip function.
      MATERIALS AND METHODS: Longitudinal strips were removed from ventral and dorsal
      detrusor of age matched control, 2-week diabetic, 2-week obstructed and 2-week
      obstructed diabetic rats. Contractile responses to electrical field stimulation,
      carbachol, adenosine triphosphate, KCl and phenylephrine, and relaxations in
      response to norepinephrine and isoproterenol were measured. RESULTS: Bladders
      from diabetic, obstructed and obstructed diabetic rats were 1.6-fold, 2.6-fold
      and 3.6-fold heavier than those from controls. Responses of bladder strips from
      diabetics to all stimuli were similar to those of controls. Strips from
      obstructed rats were significantly less responsive to norepinephrine than those
      from controls or diabetics and strips from obstructed diabetics were
      significantly less responsive to norepinephrine and isoproterenol than those from
      all other groups. Strips from obstructed diabetics had significantly decreased
      responses to field stimulation, while responses to carbachol were decreased to a
      lesser extent. Responses of strips from obstructed rats to field stimulation were
      also decreased compared with controls but were significantly greater than those
      of the obstructed diabetic group. Responses to adenosine triphosphate, KCl and
      phenylephrine were similar in all groups. CONCLUSIONS: The combination of outlet
      obstruction and diabetes mellitus causes significant increases in bladder mass
      compared with either diabetes or obstruction alone. Bladder strips from
      obstructed diabetics show characteristics of denervation accompanied by
      alterations in beta-adrenergic function, suggesting that the coexistence of
      outlet obstruction and diabetes increases the rate of development of bladder
      decompensation.

PMID- 14713858
TI  - Electrical characteristics of suburothelial cells isolated from the human
      bladder.
AB  - PURPOSE: We measured the membrane electrical characteristics as well as the
      response to adenosine triphosphate of cells isolated from the suburothelial layer
      of the bladder. MATERIALS AND METHODS: Suburothelial cells were isolated from
      biopsy samples of human bladder by collagenase disruption. Electrophysiological
      measurements were done under current and voltage clamp to record membrane
      potential and ionic currents using patch pipettes with a K+ based filling
      solution. Intracellular [Ca2+] was measured with Fura-2. RESULTS: Cells were
      different from epithelial cells by their spindle-shaped appearance with
      projections at either end. The cells stained for vimentin but epithelial and
      smooth muscle cells did not. The cells had small membrane capacitance (27 +/- 16
      pF) and a specific membrane resistance of 90 +/- 48 x 10(9) Omega cm2. Average
      membrane potential was -63 +/- 14 mV but cells showed spontaneous spikes or
      random fluctuations of membrane potential. A small net inward current was
      superimposed by a larger outward current. Inward current was attenuated by the
      removal of extracellular Ca. Outward current showed large spontaneous
      fluctuations and was greatly decreased by 30 mM tetraethyl ammonium chloride.
      Adenosine triphosphate (30 to 100 microM) elicited an inward current of about 50
      pA and large intracellular Ca2+ transients. CONCLUSIONS: These cells are
      electrically active which, in conjunction with the previous observation of
      connexin 43 labeling, suggests that they could act as an electrical network. A
      quantitative model of voltage distribution in such a network after the generation
      of inward current suggests that individual cells could not act as pacemakers, but
      rather a group of simultaneously activated cells could exert a peripheral
      excitatory effect that would amplify the magnitude of the original response. The
      implications of this in terms of bladder sensation are discussed.

PMID- 14713859
TI  - Urogenital tract expression of enhanced green fluorescent protein in transgenic
      mice driven by a smooth muscle gamma-actin promoter.
AB  - PURPOSE: Our understanding of urogenital tract development and its response to
      disease or injury is hindered by complex interactions between epithelial and
      mesenchymal cells, and the difficulties in studying either component in
      isolation. We investigated whether transgenic mice could be generated to express
      enhanced green fluorescent protein (EGFP) in smooth muscle cells (SMCs) and
      whether such cells could then be purified using flow cytometric sorting to
      isolate RNA to be used in future gene expression assays. MATERIALS AND METHODS: A
      13.7 kb mouse smooth muscle gamma-actin promoter fragment was ligated to an EGFP
      reporter gene and microinjected into male mouse pronuclei. Adult transgenic mice
      were sacrificed and urogenital tissues were removed for histological and
      immunohistochemical studies. In other animals conditions were determined for
      dissociating bladder cells and the subsequent purification of bladder SMCs by
      sorting. RESULTS: Six lines of transgenic mice were generated (transgene copy
      numbers 1 to 30). EGFP was expressed in all smooth muscle beds examined except
      those associated with small blood vessels. EGFP levels appeared to correlate with
      transgene copy number. Histological and immunohistochemical analysis confirmed
      that reporter gene expression was restricted to SMCs of all tissues examined.
      Parameters for generating bladder cell suspensions were established and EGFP
      labeled bladder SMCs were identified by flow cytometric analysis. CONCLUSIONS:
      Several lines of transgenic mice have been generated in which SMCs of urogenital
      tissues have been labeled with EGFP and pure populations of SMCs have been
      obtained. The methods established for the rapid dissociation and purification of
      bladder SMCs should minimize degradative changes. These approaches may enable us
      to address issues involving bladder SMC development and differentiation as well
      as the response to injury and disease by performing transcriptome wide analyses
      on purified SMC populations.

PMID- 14713860
TI  - Urogenital alterations in aged male caveolin-1 knockout mice.
AB  - PURPOSE: Caveolae are flask-shaped invaginations of the plasma membrane formed by
      the oligomerization of caveolins. Because only smooth muscle contains all
      caveolin (Cav) family members (Cav-1, 2 and 3), we examined the contribution of
      each caveolin to urogenital smooth muscle structure/function. MATERIALS AND
      METHODS: WT, Cav-1, 2, 3 and -1/3 knockout (KO) mouse bladders were characterized
      by Western blot, co-immunoprecipitation, immunofluorescence microscopy, electron
      microscopy, histochemistry and pharmacological techniques. Cystometric analysis
      was performed in conscious, freely moving mice. Other urogenital organs were
      investigated by histological analysis. RESULTS: The loss of bladder Cav-1 results
      in a marked decrease in Cav-2 but not Cav-3 expression. Ablation of Cav-3 fails
      to alter Cav-1 or Cav-2 expression. Deletion of Cav-1 results in the almost
      complete loss of caveolae, while Cav-2 KO and Cav-3 KO mouse smooth muscle showed
      a normal number of caveolae. The loss of Cav-1 generated caveolae led to
      significant urogenital changes in male mice (most marked by 12 months of age),
      namely 1) bladder weight-to-body weight ratios were increased, 2) the bladder
      smooth muscle layer was thickened, 3) the bladders had increased baseline,
      threshold and spontaneous pressures, 4) bladder strips showed a decreased
      contractile response to carbachol and KCl, and 5) these smooth muscle changes
      were accompanied by marked fluid accumulation in the prostate and seminal
      vesicles, with intracellular vacuolization in the kidneys. As such, male Cav-1 KO
      mice may be a useful animal model for studying LUTD (lower urinary tract
      dysfunction) that is so prevalent in aging male patients. CONCLUSIONS: The loss
      of Cav-1 and, thus, of most smooth muscle cell caveolae results in significant
      bladder dysfunction and urogenital organ changes in aged male mice.

PMID- 14713861
TI  - Inhibition of hyperreflexia by vaginally administered oxybutynin: a novel rabbit
      model.
AB  - PURPOSE: The rabbit has proved to be an excellent model in which to study lower
      urinary tract function and pathological mechanisms involved in specific forms of
      lower urinary tract dysfunctions, including those involved with partial outlet
      obstruction (benign prostatic hyperplasia), erectile dysfunction, bladder
      instability and ischemic bladder disease. The current study describes a model of
      bladder instability induced in female rabbits and its use in developing a novel
      form of vaginal treatment for this instability. MATERIALS AND METHODS: A total of
      18 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 monitoring bladder pressure and
      for cystometry. A ligature was placed around the urethra just distal to the
      bladder neck to prevent leakage through the urethra and generate unstable bladder
      contractions. After initial cystometry the bladder was emptied and then filled to
      30 ml. Acetylcholine (Ach) was administered into the vesical artery at 15-minute
      intervals for 2 hours. Hyperreflexia usually developed within 30 minutes. Vaginal
      oxybutynin (low and high dose) was applied and the effect on cystometry, the
      response to Ach, and the amplitude and frequency of hyperreflexia was determined.
      RESULTS: Each dose of oxybutynin increased bladder capacity and improved
      compliance. The high oxybutynin dose completely inhibited the response to Ach and
      significantly decreased micturition pressure. The high dose decreased uninhibited
      bladder contraction peak pressure in a time dependent manner to a greater extent
      than it decreased uninhibited contraction frequency. The low dose of oxybutynin
      had no effect on micturition pressure, significantly inhibited the response to
      Ach and hyperreflexia amplitude to approximately 40% of control values, and had
      little effect on hyperreflexia frequency. CONCLUSIONS: Vaginally delivered
      oxybutynin was effective in improving bladder compliance, inhibiting intra
      arterial Ach stimulated bladder contractions and significantly decreasing the
      amplitude of hyperreflexia. Vaginal oxybutynin had a more potent effect on the
      evoked response to Ach and on hyperreflexia than it did on micturition pressure.

PMID- 14713862
TI  - Roles of opiate in lower urinary tract dysfunction associated with spinal cord
      injury in rats.
AB  - PURPOSE: It has been reported that the opiate receptor system in the spinal cord
      is involved in bladder and urethral function. We determined whether U-50488
      (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide),
      a kappa opioid receptor agonist, could decrease detrusor-sphincter dyssynergia
      (DSD) and, thus, improve voiding efficiency in conscious, spinal cord injured
      (SCI) rats. MATERIALS AND METHODS: Experiments were done in female Sprague-Dawley
      rats in which the spinal cord was completely transected at the T6-8 level 4 weeks
      prior to performing cystometry while conscious and held in a restraining cage.
      Experiments were also performed in normal spinal cord rats. Saline was infused
      (0.1 ml per minute) via the cystostomy catheter into the bladder. Voiding
      efficiency was determined by measuring voided and residual volumes. After
      performing a control cystometrogram increasing doses of U-50488 (0.01, 0.1, 1 and
      10 mg/kg) were administered intravenously at 1-hour intervals. The effects of nor
      binaltorphimine dihydrochloride, a kappa opioid receptor antagonist, on U-50488
      induced changes in voiding parameters were also examined. RESULTS: A high dose of
      U-50488 (1 to 10 mg/kg) significantly decreased contraction amplitude and bladder
      capacity (p <0.01 to 0.05) in normal spinal cord and SCI rats. A low dose of U
      50488 (0.01 mg/kg) increased voiding efficiency by 32.7% without decreasing
      bladder capacity in SCI rats. Nor-binaltorphimine hydroparameters counteracted
      the effect of U-50488 induced changes. CONCLUSIONS: These results suggest that
      the kappa opioid receptor system is related to DSD caused by spinal cord injury.
      The kappa opioid receptor agent is believed to have therapeutic potential for
      treating DSD associated with SCI.

PMID- 14713863
TI  - Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries.
AB  - PURPOSE: The current in vitro study was performed to investigate intracellular
      mechanisms underlying prostaglandin E1 (PGE1) elicited vasodilation in isolated
      penile resistance arteries and evaluate whether there may be interactions with
      the nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway.
      MATERIALS AND METHODS: Second or third order branches of the horse deep
      intracavernous penile artery were mounted in microvascular myographs. The
      vasodilator effects of PGE1 and cyclic adenosine 3',5'-monophosphate (cAMP)
      elevating agents were evaluated in the absence and the presence of inhibitors of
      the adenylate cyclase/cAMP and the NO/cGMP pathways. RESULTS: PGE1, the adenylate
      cyclase activator forskolin, and the phosphodiesterase types 3 and 4 inhibitors
      milrinone and rolipram, respectively, dose dependently relaxed penile resistance
      arteries with rolipram being the most potent of the 4 relaxant agents. Threshold
      concentrations of rolipram markedly enhanced PGE1 elicited relaxations. The
      inhibition of cAMP dependent protein kinase decreased relaxant responses to PGE1,
      forskolin and rolipram. Neither mechanical endothelial cell removal nor the
      blockade of NO synthase or guanylate cyclase altered PGE1 relaxant responses.
      However, combined treatment with blockers of cAMP dependent protein kinase and
      cGMP dependent protein kinase unmasked an inhibitory effect of the latter on
      relaxations induced by PGE1 and forskolin. CONCLUSIONS: These results provide
      evidence for cAMP involvement in PGE1 elicited vasodilation of penile resistance
      arteries. They underline the importance of the adenylate cyclase/cAMP pathway in
      the relaxation of penile erectile tissue. Moreover, cAMP elevating agents seem to
      cross-activate cGMP dependent protein kinase, thus, interacting downstream with
      the NO/cGMP cascade.

PMID- 14713864
TI  - [The fight against addiction to smoking is difficult, even for future
      physicians].

PMID- 14713865
TI  - [Information for the patient. Application of the law dated March 4, 2002 (2/2)].

PMID- 14713867
TI  - [Knowledge, opinions and tobacco consumption in a French faculty of medicine].
AB  - OBJECTIVE: Tobacco consumption among French physicians is regularly followed-up
      and well-known; however, there is little information concerning the smoking
      habits of medical students even though they are the physicians of the future. How
      do they behave? Do they smoke? More or less than the other populations of the
      same age? METHOD: All the students of a Parisian medical school were surveyed
      with a self-questionnaire completed and collected just before the exams at the
      end of the year. The questionnaire incorporated both past and present smoking
      habits and also the students' knowledge and opinions on tobacco consumption.
      RESULTS: A total of 681 students replied. More than one-third were smokers
      (34.6%) among which 21.0% smoked every day and 13.6% smoked occasionally. Gender
      had no influence on prevalence rate and both men and women smoked a comparable
      number of cigarettes per day (males 12.0 cig/day, females 10.4 cig/day). Eleven
      percent were former smokers and 68.4% would like to quit. Nearly 100% believed
      that cigarette smoke can bother others and 75% felt they were exemplary figures
      for others on the subject of tobacco use. Finally, two-thirds of the students
      smoked light cigarettes. CONCLUSION: The smoking habits of medical students are
      similar to those of the general population of the same age. It is necessary to
      develop specific prevention programs for medical students because they will play
      an important public health role in the future in reducing the prevalence of
      tobacco consumption in France.

PMID- 14713868
TI  - [The protection of persons and biomedical research in France. A multicentre study
      of 10 committees].
AB  - OBJECTIVE: Since 1988, any human biomedical research protocol in France must be
      submitted to a committee for the protection of persons participating in
      biomedical research programs (Comite consultatif de protection des personnes dans
      la recherche biomedicale (CCPPRB). This study is one of the first to analyse the
      functioning of the French CCPPRB at the onset of the application in 2004 of a
      European ruling on drug research, so as to study the pertinence of the opinions
      and the necessity or not of homogenising committee habits. METHOD: Ten CCPPRB
      participated in the study. An external observer visited all the centres. Three
      methodological instruments were used: semi-directive interviews with categories
      representative of the committee, analysis of the observer's documents and
      analysis of the discussions during dossier sessions. RESULTS: The habits are
      heterogenic regarding the crucial definitions represented by biomedical research
      and the limits of the latter. In half of the committees, the decision to
      investigate a protocol is taken by the president alone. All the dossiers are
      studied by one or several reporters, but not always within discussion sessions,
      hence underlining the need to respect the multidisciplinarity within a CCPPRB.
      CONCLUSION: These results show the importance of developing training courses for
      the members of a CCPPRB and the need to consecrate means for these CCPPRB,
      representing the democratic authority for the analysis of the protocols.

PMID- 14713869
TI  - [The association of Pneumatosis intestinalis and portal venous gas].
AB  - INTRODUCTION: Pneumatosis intestinalis is the presence of air in a wall of a
      section of the digestive tract. Portal venous gas is a radiological sign that
      corresponds to the presence of air in the portal vein. Their association,
      observed among others in certain pathologies such as the blunt abdominal trauma,
      endoscopic procedures or anaerobic infections, is a factor of severity.
      OBSERVATION: We report a case of Pneumatosis intestinalis and portal venous gas
      secondary to uterine gangrene after caesarean operation in a 16 year-old woman.
      CONCLUSION: Diagnosis of Pneumatosis intestinalis in association with portal
      venous gas is an emergency indication for surgery in the case of septicaemia,
      although exhibiting a high rate of complications and mortality.

PMID- 14713870
TI  - [Management of a patient receiving thalidomide].
AB  - THE USE OF A DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is
      currently available in France for nominative or cohort use with a temporary
      marketing authorisation (TMA). It is only prescribed and delivered in hospital
      settings. SIX OFFICIAL INDICATIONS: Its current indications are principally
      lepromatous nodular erythema, severe aphtosis, Jessner-Kanoff's cutaneous
      lymphocyte infiltration, discoid lupus erythematosis, chronic graft-versus-host
      reactions, and relapsed and or refractory multiple myeloma (after the failure of
      standard therapies). In the majority of cases, thalidomide is a last resort
      treatment of rare pathologies. On withdrawal, it is responsible for more or less
      long-term recurrences of the disease that require its re-introduction.
      SURVEILLANCE IS CRUCIAL: The side effects induced by thalidomide must never be
      forgotten, notably its teratogenic effects and its often irreversible
      neurotoxicity. The latter limit the long-term use of thalidomide and imply strict
      rules for its prescription and surveillance (efficient contraception, clinical
      neurological examinations, electroneurophysiological controls).

PMID- 14713871
TI  - [Thoracic pain of oesophageal origin. Diagnostic management and treatment].
AB  - FROM AN ETIOLOGICAL POINT OF VIEW: Thoracic pain is a frequent symptom. Before
      confirming the oesophageal origin of the pain, a coronary disease must be
      excluded. Two principle causes are source of thoracic pain of oesophageal origin:
      gastro-oesophageal reflux disease and oesophageal motility abnormalities. THE
      DIAGNOSTIC APPROACH: This must include the questioning of the patient and the
      usual paraclinical examinations. To confirm the diagnosis, these examinations
      must establish a chronological relationship between the symptoms and the
      abnormalities. For economic reasons, following a normal gastroscopy, there is a
      tendency to propose an empirical proton pump inhibitor (PPI) test rather than a
      24 hour pH-metry antireflux as first line. The improvement or even the
      disappearance of the symptoms confirms the diagnosis; long-term treatment with a
      double dose of PPI should therefore be envisaged. The pH-metry with search for
      results should be proposed to the non-responders and to patients with atypical
      reflux manifestations. Dysphagia and odynophagia suggest an oesophageal motility
      disorder that basal manometry should confirm. A chronological relationship is
      rarely revealed, but the sensitivity of the pH-meter can be enhanced by
      provocation tests. REGARDING TREATMENT: Other than achalasia, treatment of the
      other spastic-like motor disorders is not well codified. Diltiazem is efficient.
      Some patients exhibit a hyperalgic oesophagus. The physiopathological mechanisms
      are still theoretical. Low dose tricyclic antidepressors and psychological
      management are useful.

PMID- 14713872
TI  - [The EPO beta injection pen in patients in maintenance dialysis or predialysis:
      acceptability, satisfaction and cost assessment].
AB  - OBJECTIVE: This study was aimed at evaluating the acceptability and economic
      impact of the utilisation of Reco-Pen, an injection pen equipped with cartridges
      in patients requiring treatment with recombinant human erythropoietin (rHu-EPO).
      METHOD: A random sample of 124 patients in maintenance dialysis or in pre
      dialysis were enrolled in 42 French centres in 2001. 87% of patients were in
      maintenance therapy and the rest in correction phase. A nurse was dedicated in
      each centre to educate and assist the patients during the whole study period (2
      months). The economic analysis compared the treatment costs in the subgroup of
      108 patients already treated at inclusion. RESULTS: The satisfaction scores were
      positive in 80% of patients in terms of improved autonomy and comfort and 93%
      declared themselves ready to continue using the pen. After a mean 2-month period
      of follow up, the self-injection rates rose from 21 to 53%. ECONOMICAL SYNTHESIS:
      The switch to Reco-Pen of 100 patients in maintenance therapy was associated with
      a total savings of 22,449 Euro, decomposed as follows: 18,725 Euro corresponding
      to savings in rHu-EPO, 3,500 Euro corresponding to the non-reimbursed honoraria
      of the private nurses, and 224 Euro in productivity savings in time spent by the
      centres' nurses, i.e. an accumulation of 10.4 hours.

PMID- 14713873
TI  - [Osteoporosis and arthrosis. Epidemiology, economical aspects and management].

PMID- 14713874
TI  - [Tetanus in a HIV-positive polytraumatised patient. Interview by J-Ph. Madiou].

PMID- 14713876
TI  - [Complete arrhythmia due to atrial fibrillation: decrease or slow down?].

PMID- 14713878
TI  - [Epidemiological characteristics of elderly dialysed patients aged 75 and more.
      Study conducted in the Provence-Alpes-Cote d'Azur region of France].
AB  - INTRODUCTION: One of the consequences of an ageing French population is the large
      number of elderly patients with end stage renal failure (ESRF). Nephrologists
      will be increasingly confronted with the growing number of elderly patients and
      the sometimes-precarious health of the extremely elderly. OBJECTIVE: To describe
      the epidemiological characteristics of the populations of patients over 75 years
      in ESRF, treated by dialysis in the Provence Alpes Cote d'Azur region (Paca) in
      1999. METHOD: Cross-sectional survey. RESULT: Of the 2347 patients treated by
      dialysis and resident in the Paca region, 25,1% are aged 75 or more. The
      prevalence for this age group is of 1428 patients per million persons (pmp)
      versus 429 pmp for those aged under 75 years. Elderly patients are more
      frequently treated by dialysis in centres, with shorter dialysis duration. They
      have more complications related to treatment (perdialytic hypotension, irregular
      cardiac rhythm), more dependence and more frequently exhibit comorbidity, with
      the exception of hepatitis C which is less frequent in this population
      (p<0.0001). The number of patients aged 75 and over treated with dialysis
      increased 53% between 1995 and 1999 in the Paca region compared with an overall
      increase of 17% during the same period. The recourse to hemodialysis in a centre
      for these patients increased by 39.4% whereas it has decreased by 2.4% in younger
      populations (p<0.0001). In fact, the use of autodialysis has risen enormously:
      +309% for those aged 75 years and more and +88.1% for others. CONCLUSION: The
      increase in the prevalence of elderly people undergoing dialysis will present
      problems due to a saturation point which is now being reached in dialysis
      centres. It is clear that those who forecast health care provisions will need to
      adapt the supply and demand better to the requirements of the population.

PMID- 14713879
TI  - [Management of acute community-acquired pneumonia in a health centre. Assessment
      of 101 cases using the retrospective clinical audit method].
AB  - OBJECTIVE: To assess the conformity of practitioners' practices in the management
      of community acquired pneumonia with the French Agence Nationale d'Accreditation
      et d'Evaluation en Sante (Anaes) guidelines. METHODS: We retrospectively reviewed
      a random sample of 210 medical records which included a principal or associated
      diagnosis of pneumonia in a French university hospital. RESULTS: A hundred and
      one medical records were assessable. Sixty-two patients were high risk (Pneumonia
      Severity Index class IV or V of the prediction rule of Fine et al.), and 10
      patients were admitted into an intensive care unit. The overall in-hospital
      mortality was 14 patients [8-22]. The level of care was appropriate according to
      the guidelines in 40 cases ([30-50)]. Seven patients did not require
      hospitalisation, 31 patients required admission into a medical department, 56
      patients into an intensive care unit and 7 patients were managed in non specified
      conditions. Eighteen patients ([11-27]) had appropriate microbiologic
      investigations. Forty-three patients (([33-53]) received antibiotics within 8
      hours of arrival. Empirical antibiotic treatment (dosage and molecule) was
      appropriate in 38 patients ([28-48]). There was no significant relationship
      between compliance with the guidelines and in-hospital mortality. CONCLUSION: The
      rate of conformity of practitioners' practices with the Anaes guidelines for
      management of community-acquired pneumonia is low in our hospital. It could be
      improved by active implementation of these guidelines.

PMID- 14713880
TI  - [Acute poisoning caused by intravenous arsenic].
AB  - INTRODUCTION: During acute sodium arsenite intoxication, absorption is usually
      oral and rarely respiratory. We report the first case of acute intoxication by
      intravenous administration, with pharmacokinetic modelling. OBSERVATION: A 38
      year-old man had attempted suicide by injecting a solution of sodium arsenite.
      The first symptoms upon admission to an emergency unit were hypotension,
      electrocardiographical disorders with prolonged QT and aqueous diarrhoea.
      Dimercaprol therapy was immediately set-up but was stopped on 48 hours later
      because of acute renal failure. Eleven successive blood and urine samples were
      drawn. Hairs and nails were sampled at the 130th hour. Results of the confirmed
      the elevated arsenic concentrations in all the samples. The pharmacokinetic
      parameters were computed following a two-compartment model with intravenous
      administration and with elimination from the central compartment. DISCUSSION:
      During this acute intravenous induced arsenic poisoning, the symptomatology was
      comparable to that following oral intoxication. The chelating treatment, although
      rapidly suspended, obviously contributed to survival. The eventual occurrence of
      other cases should permit the adaptation of therapeutic protocols to these types
      of intoxication.

PMID- 14713881
TI  - [The onset of pneumoperitoneum with respiratory failure during a bronchial
      fibroscopy].

PMID- 14713882
TI  - [Imaging strategy for cervical spine injury].
AB  - MAKING THE DIAGNOSIS: Exploration strategies when faced with a suspected spine
      injury have improved with the recent development of new imaging techniques
      (notably the helical CT scan). A selection must be made between the techniques
      available in order to optimise diagnostic habits. THE FUNDAMENTAL POINTS: The
      clinical examination identifies the small group of patients that does not require
      radiographic exploration. When cervical lesions exist, they are often multiple
      and layered. This justifies the fact that, if an exploration of the cervical
      spine is proposed, it should be complete and include the upper and lower hinges.
      The quality of the standard images (face, profile, mouth open) varies greatly.
      Their negative quality and predictive value decreases when the severity of the
      injury increases. PARTICULAR EXAMINATIONS: Scanning is the most efficient
      technique for not only detecting but also formally eliminating an injury. Its
      indications should therefore be extended but also limited to a selected
      population. The MRI is currently a second line examination, indicated for any
      suspicion of a neurological lesion, notably of the bone marrow. Lesions of the
      ligaments are often missed and should be systematically searched for using
      dynamic imaging. These can be done at distance from the injury.

PMID- 14713883
TI  - [Osteopathies that weaken HIV-infected patients].
AB  - OSTEOPOROSIS AND OSTEOPENIA: The use of multiple antiretroviral therapies has
      transformed the prognosis of HIV infection. However, the potential disadvantages
      of these treatments have rapidly appeared: lipodystrophy, cardiovascular
      complications and, more recently bone affections with osteonecrosis, followed by
      other weakening osteopathies (osteoporosis and osteopenia). Osteoporosis is a
      reduction in bone mineral density (BMD) leading to a high risk of fracture. It is
      measured by dual energy x-ray absorptiometry and is defined by a T-score<-2.5
      standard deviations from the mean value of a young adult. Osteopenia corresponds
      to low bone density with, avec -1>T-score>-2.5. REGARDING THE AVAILABILITY OF
      RETROVIRAL AGENTS: During HIV infections, an osteopathy (most often osteopenia)
      is observed in a quarter to more than half of patients who have never received
      antiretroviral agents, and in up to three quarters in those in whom treatment in
      ongoing. The transversal nature of the majority of the studies, the heterogeneity
      of the treatments, the inclusion of both male and female patients in some
      studies, and the differences in the results observed do not permit one to draw
      any conclusions as to the possible responsibility of antiretroviral agents. An
      association between an osteopathy and a lipodystrophy is inconstant. Lastly, the
      substitution of a class of a antiretroviral agents by another does not lead to
      any significant modification in BMD. THE MECHANISM OF OCCURRENCE OF AN
      OSTEOPATHY: Has not been clearly established. The modifications in serum
      concentrations of biochemical markers of bone formation and resorption observed
      in HIV-infected patients and their evolution under antiretroviral treatment,
      suggest a viral origin, mediated by pro-inflammatory cytokines. The rare in vitro
      studies, or on animal models, are contradictory, with the results of clinical
      trials regarding the inherent role of antiretroviral drugs. However, it is
      probable that the classical risk factors for osteoporosis are often implied.

PMID- 14713884
TI  - [Congress of the International Diabetes Federation (IDF-Paris 2003)].

PMID- 14713887
TI  - Effective treatment of the central nervous system in lysosomal storage diseases:
      save that brain!

PMID- 14713888
TI  - Effect of a gastrin/cholecystokinin B receptor antagonist, S-0509, on the
      omeprazole-induced proliferation of gastric mucosa in rats.
AB  - Hypergastrinemia is known to cause hyperplasia of the gastric mucosa, especially
      in gastric enterochromaffinlike (ECL) cells. In some clinical conditions causing
      hypergastrinemia, such as long-term gastric-acid inhibition and gastric-mucosa
      atrophy, hyperplastic ECL cells may develop into gastric carcinoid tumors. A
      newly developed gastrin-receptor antagonist, S-0509, has been reported to block
      gastrin-induced stimulation of gastric-acid secretion. We therefore investigated
      whether S-0509 inhibits the omeprazole- and gastrin-stimulated hyperproliferation
      of gastric mucosa, especially of ECL cells. Daily administration of omeprazole
      and gastrin in male Sprague-Dawley rats induced marked hypergastrinemia and
      increased proliferation of gastric-mucosa cells. The numbers of ECL cells and of
      ECL cells producing messenger RNA for regenerating gene, a potent growth factor
      for gastric-mucosa cells, were also augmented by long-term administration of
      omeprazole and gastrin. Coadministration of S-0509 with omeprazole or gastrin
      almost completely inhibited the omeprazole- and gastrin-induced changes in
      gastric mucosa, including mucosal thickening and ECL hyperplasia. S-0509 did not
      induce gastric-mucosa atrophy, even when administered for as long as 4 weeks. In
      summary, we have found that a newly developed gastrin receptor antagonist, S
      0509, inhibits omeprazole- and gastrin-induced mucosal hyperplasia, especially
      ECL-cell hyperplasia, in rats.

PMID- 14713889
TI  - Urinary clearance of albumin is critically determined by its tertiary structure.
AB  - The excretion of serum albumin in the urine is considered the net result of renal
      glomerular filtration and tubular uptake. During routine experiments, we observed
      that a batch of tritium-labeled albumin yielded anomalous results, being excreted
      in the urine of isolated perfused kidneys at 10 times the rate of normal
      tritiated albumin. This anomalous albumin, when simultaneously studied with
      normal carbon 14-labeled albumin, exhibited 10 times greater excretion than
      normal [(14)C]albumin. Anomalous albumin could not be reversed to normal albumin
      by means of conditioning with blood. In vivo clearances of anomalous albumin
      could not be quantitated because anomalous albumin is degraded during
      circulation. Anomalous albumin appeared to have the same molecular size (as
      determined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      capillary electrophoresis, and gel chromatography) and isoelectric-point profile
      (2-dimensional electrophresis) as normal albumin. Normal albumin could be
      transformed to anomalous albumin with alkali/heat treatment. Reverse-phase high
      pressure liquid chromatography analysis of fragments from tryptic digests of
      anomalous albumin, alkali/heat-treated albumin, and normal albumin suggest that
      anomalous albumin and alkali/heat-treated albumin have altered tertiary
      structure, possibly as a result of denaturation and disulfide exchange. These
      studies show that the tertiary structure of albumin, beyond simple size and
      charge, is a critical determinant for albumin processing by the kidney and
      suggest that a specific albumin-recognition event by the kidneys is critical to
      normal renal handling of albumin.

PMID- 14713890
TI  - Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic
      decompensation presentation with trientine and zinc.
AB  - We have treated 9 patients who presented with hepatic decompensation resulting
      from Wilson's disease with a combination of trientine and zinc, generally for at
      least 4 months, followed by transition to zinc maintenance therapy. All of these
      patients had hypoalbuminemia, all but 1 had hyperbilirubinemia, and 7 had
      ascites. All of these patients would have been candidates for liver
      transplantation on the basis of their initial Child-Turcotte-Pugh (CTP) scores.
      The minimal listing criteria for transplant candidates is a score greater than 7.
      Eight of the 9 patients had demonstrated a CTP score of 10 or higher. The other
      scoring system that has been used in Wilson's disease to determine need for
      transplantation is the prognostic index of Nazer, in which a score over 6
      indicates that the patient is unlikely to survive without a transplant if treated
      with penicillamine. Two of our patients had Nazer scores higher than 6. With our
      medical therapy, all 9 of these patients have recovered normal liver function as
      reflected by normalization of their CTP scores to 5. Because of coexisting
      neurologic disease, 1 of our 9 patients was initiated on a neurologic protocol
      and by chance randomized to receive tetrathiomolybdate (TM) and zinc after 2
      weeks of trientine/zinc treatment. This patient's liver function recovered much
      more rapidly than did that of the other 8 patients, all of whom were treated with
      trientine/zinc, suggesting that TM therapy offers a further advantage. In
      summary, we were able to take 9 patients who presented with liver failure -8 of
      whom had CTP scores indicating a potential need for liver transplantation and 2
      of whom had Nazer prognostic scores indicating that they were not likely to
      survive if treated only with penicillamine - and treat them medically, with
      recovery in all 9. We believe the trientine/zinc combination therapy should be
      the standard for initial treatment of liver failure in Wilson's disease because
      its efficacy is equal or slightly superior to that of penicillamine and because
      it has a much lower incidence of side effects. Moreover, TM warrants study to
      determine whether therapy for hepatic Wilson's disease can be further improved.

PMID- 14713891
TI  - Impairment of blood rheology by cholestatic jaundice in human beings.
AB  - Bilirubin and bile acids may affect erythrocytes. We investigated blood viscosity
      and erythrocyte structure in patients with cholestatic jaundice ex vivo and
      studied the short-term effects of bilirubin and bile acids in vitro. Seventeen
      patients with cholestatic jaundice and controls were studied. Whole-blood
      viscosity (adjusted hematocrit 45%) at high (94.5 sec(-1)) and low (0.1 sec(-1))
      shear rate and plasma viscosity were measured. Erythrocyte structure was assessed
      in wet preparations of fixed cells. In vitro whole blood was incubated with
      increasing concentrations of bilirubin (83% conjugated) and bile acids (cholic,
      lithocholic, deoxycholic, and chenodeoxycholic acid) and the abovementioned
      investigations were performed. In patients we observed increased whole-blood
      viscosity at high shear rate (5.82 +/- 0.69 vs 5.04+/- 0.27 mPa. sec, P =.0001),
      plasma viscosity (1.48 +/- 0.22 vs. 1.23 +/- 0.07 mPa. sec, P =.0004), and
      fibrinogen level (4.70 +/- 0.98 g/L vs 2.63 +/- 0.21 g/L, P < 0.001) were
      observed. The incubation of normal erythrocytes in patients' plasma confirmed an
      increase in blood viscosity at high shear rate. Erythrocytes from patients with
      jaundice demonstrated a slight degree of stomatocytic shape transformation (P
      <.0001). In vitro, bilirubin did not affect erythrocyte shape. Cholic and
      lithocholic acids caused a slight stomatocytic shape transformation, whereas
      deoxycholic acid and chenodeoxycholic acid influenced neither blood viscosity nor
      erythrocyte structure. Patients with cholestatic jaundice have increased whole
      blood and plasma viscosity and slightly altered red blood cell shape, possibly
      the result of a combination of increased levels of bilirubin and bile acids plus
      an acute-phase reaction.

PMID- 14713892
TI  - Delivery of recombinant gene product to canine brain with the use of
      microencapsulation.
AB  - An alternative approach to somatic gene therapy is to deliver a therapeutic
      protein by implanting "universal" recombinant cells that are immunologically
      protected from graft rejection with alginate microcapsules. This strategy has
      proved successful in reversing pathologic conditions in several rodent models of
      human disease (dwarfism, lysosomal storage disease, hemophilia, cancer). In
      particular, neurologic disease and behavioral deficit in the mouse model of a
      neurodegenerative disease (mucopolysaccharidosis [MPS] VII) were significantly
      improved through the intraventricular implantation of the recombinant
      encapsulated cells. Here we report the feasibility of delivering recombinant gene
      products to the central nervous systems (CNSs) of dogs, first using human growth
      hormone as a marker for delivery in normal dogs and then using alpha-iduronidase
      as a therapeutic product for delivery in the MPS I dog that is genetically
      deficient in this lysosomal enzyme. Madin-Darby canine kidney cells were
      genetically modified to express either human growth hormone or canine alpha
      iduronidase, then enclosed in alginate-poly-l-lysine-alginate microcapsules of
      about 500 microm in diameter. The encapsulated cells were implanted into the
      brain under steoreotaxic guidance. The brains were monitored with computed
      tomographic scans before and after surgery and examined biochemically and
      histologically. Delivery of gene products, as measured in the plasma and
      cerebrospinal fluid sampled periodically through 21 days or in various regions of
      the brain after death showed that the delivery of both gene products was
      extremely low but detectable. However, we noted extensive inflammatory reactions,
      both at the sites of implantation and in the immediate vicinity of the implanted
      microcapsules. Hence for this technology to be applicable to the CNSs of larger
      animals and human beings, a more accurate and less invasive neurosurgical
      procedure, more biocompatible microcapsule-recombinant cell combinations, and
      higher output of recombinant products must be developed.

PMID- 14713893
TI  - Regulation of hemoglobin affinity for oxygen by carbonic anhydrase.
AB  - We studied the effect on hemoglobin (Hb)-oxygen affinity induced by changes in
      carbonic anhydrase (CA) activity. Oxygen partial pressure at the 50% saturation
      of Hb (P(50)) in human blood was measured as CA activity was inhibited to varying
      degrees with acetazolamide (AZ; 100 and 200 microg/mL). Transient but significant
      change in P(50) was observed when AZ was administered and the CO(2) concentration
      was changed from 10% to 5%. Finally, the differences induced with AZ were
      attenuated when the blood sample was subjected to 4 hours of tonometry. The
      findings in this study could be accounted for by reduced velocity of pH changes
      caused by the inhibition of CA by AZ. We conclude that CA can change Hb's
      affinity for oxygen by controlling the movement of CO(2) gas between air and
      liquid compartments.

PMID- 14713894
TI  - Helicobacter pylori infection inhibits healing of the wounded duodenal epithelium
      in vitro.
AB  - Helicobacter pylori (Hp) infection causes duodenal ulcers, delays the healing of
      such ulcers, and is associated with ulcer recurrence. The pathogenic mechanisms
      involved in Hp-induced duodenal mucosal injury and delay in ulcer healing remain
      unclear. In this study we sought to investigate the possible pathogenic actions
      of Hp infection and vacuolating cytotoxin (Vac A) on duodenal epithelial wound
      healing, using an in vitro wound model consisting of excisionally scraped or
      eroded IEC-6 duodenal monolayers. Two isogenic strains of Hp were used: wild-type
      strain 60190, producing Vac A; and an isogenic mutant strain, 60190-v1, that
      lacks the gene to produce the cytotoxin. The addition of Vac A-positive or Vac A
      negative Hp (50:1 ratio of bacterial to epithelial cells) to the eroded or
      "wounded" IEC-6 monolayers resulted in significant inhibition of wound
      reepithelialization. The Vac A-positive Hp produced significantly greater
      inhibition than did the Vac A-negative Hp (70% and 35% inhibition, respectively;
      P <.001). Additionally, the bacterial supernatant containing Vac A (but not the
      supernatant lacking the cytotoxin) caused significant inhibition of IEC-6 wound
      reepithelialization in the absence of Hp infection, indicating that Vac A has an
      independent inhibitory action on wound reepithelialization. The Vac A inhibition
      of IEC-6 reepithelialization correlated with down-regulation of actin stress
      fibers in the migrating cells. Epidermal growth factor (EGF) stimulated IEC-6
      wound reepithelialization with a corresponding increase in the formation of actin
      stress fiber. Vac A-positive bacterial supernatant (but not Vac A-negative
      supernatant) prevented the EGF-stimulated increase in IEC-6 actin stress fiber
      formation and wound reepithelialization. These findings demonstrate that Hp
      infection inhibits the process of duodenal epithelial wound healing. Hp
      inhibition of duodenal wound healing may therefore be an important pathogenic
      factor contributing to duodenal mucosal injury and delay in ulcer healing in
      vivo.

PMID- 14713895
TI  - Ultrastructural analysis and classification of pigment gallstones.

PMID- 14713896
TI  - Adrenoleukodystrophy: abnormal white matter signal on MRI.

PMID- 14713900
TI  - Verdict in the case of therapies versus eosinophils: the jury is still out.
AB  - Eosinophils are regarded by many as fundamental to the pathophysiology of
      allergic diseases, including asthma. An improved understanding of the mechanisms
      involved in these responses is therefore of great relevance to asthma
      pathogenesis and the development of new therapeutics. Most therapies that are
      effective in reducing allergic inflammation in animals and human subjects
      diminish tissue eosinophilia and levels of eosinophil-derived mediators. However,
      recent efforts with more selective eosinophil-suppressive therapies have failed
      to affect disease, bringing into question the role of eosinophils in asthma. This
      article will provide a brief overview of the role of eosinophils in allergic
      diseases, followed by a discussion of both eosinophil-specific and eosinophil
      selective therapeutic targets, with a focus on cell-surface molecules. The known
      and theoretic benefits and risks of these strategies will also be covered.

PMID- 14713902
TI  - Eosinophilic gastrointestinal disorders (EGID).
AB  - Primary eosinophilic gastrointestinal disorders are defined as disorders that
      selectively affect the gastrointestinal tract with eosinophil-rich inflammation
      in the absence of known causes for eosinophilia (eg, drug reactions, parasitic
      infections, and malignancy). These disorders include eosinophilic esophagitis,
      eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and
      eosinophilic colitis and are occurring with increasing frequency. Significant
      progress has been made in elucidating that eosinophils are integral members of
      the gastrointestinal mucosal immune system and that eosinophilic gastrointestinal
      disorders are primarily polygenic allergic disorders that involve mechanisms that
      fall between pure IgE-mediated and delayed T(H)2-type responses. Preclinical
      studies have identified a contributory role for the cytokine IL-5 and the eotaxin
      chemokines, providing a rationale for specific disease therapy. An essential
      question is to determine the cellular and molecular basis for each of these
      clinical problems and the best treatment regimen, which is the main subject of
      this review.

PMID- 14713904
TI  - The role of eosinophils in host defense against helminth parasites.
AB  - The precise function of eosinophils in parasitic infection in vivo remains poorly
      understood despite eosinophils having been shown to be potent effectors in
      killing parasites in vitro. Although it has long been held that the primary
      function of the eosinophil is protection against helminth parasites, there are
      little data to prove this unequivocally. Moreover, eosinophils are responsible
      for a considerable amount of inflammatory pathology accompanying helminth
      infections. This article will provide an overview of our current knowledge about
      eosinophils and their role, both protective and pathogenetic, in parasitic
      helminth infections.

PMID- 14713905
TI  - The eosinophil--quo vadis?

PMID- 14713906
TI  - Allergic rhinitis: a disease remodeling the upper airways?
AB  - The nasal and bronchial mucosa present similarities and differences. Remodeling
      is defined as "model again or differently, reconstruct" and is present in the
      airways of most if not all asthmatic patients. Even though inflammation is
      similar in allergic rhinitis and asthma, the pathologic extent of nasal
      remodeling in patients with rhinitis seems to be far less extensive than that in
      the bronchi of asthmatic patients. Epithelial damage is only minimal, and the
      reticular basement membrane does not appear to be largely pseudothickened.
      Moreover, the demonstration of fibrogenic growth factors in the nasal mucosa of
      patients with allergic rhinitis is lacking because of the paucity of studies. The
      reasons why remodeling appears to be less extensive in the nasal mucosa than in
      the bronchial mucosa are still unclear, but 2 hypotheses can be put forward. On
      one hand, the cytokine production of smooth muscle cells might partly explain
      differences in remodeling of the 2 sites of the airways. On the other hand, the
      genes of the embryologic differentiation might persist in the nose and bronchi or
      might be re-expressed in asthma and rhinitis. Because the nose is of ectodermal
      origin and the bronchi of endodermal origin, these genes might also govern
      remodeling patterns. More studies are urgently required to better characterize
      nasal remodeling in patients with rhinitis. A better understanding of nasal and
      bronchial remodeling might help to identify new pathways and new therapeutic
      strategies to reduce long-term remodeling in asthma.

PMID- 14713907
TI  - Hypereosinophilic syndrome: case presentation and update.
AB  - Persistent peripheral blood eosinophilia can be associated with a variety of
      diseases, ranging from parasitic infection to gastrointestinal disease to
      vasculitis to the hypereosinophilic syndrome (HES). Mucosal ulcerations are a
      variant presentation of the HES that appear to be markers for a mutation that
      characterizes a subgroup of patients with HES responsive to treatment with
      imatinib mesylate. We present a patient with peripheral blood eosinophilia and
      severe recurrent mucosal ulcers and discuss his presentation in the context of
      new information about the evaluation, disease progression, and treatment of HES.

PMID- 14713908
TI  - Development of the asthma control test: a survey for assessing asthma control.
AB  - BACKGROUND: Asthma guidelines indicate that the goal of treatment should be
      optimum asthma control. In a busy clinic practice with limited time and
      resources, there is need for a simple method for assessing asthma control with or
      without lung function testing. OBJECTIVES: The objective of this article was to
      describe the development of the Asthma Control Test (ACT), a patient-based tool
      for identifying patients with poorly controlled asthma. METHODS: A 22-item survey
      was administered to 471 patients with asthma in the offices of asthma
      specialists. The specialist's rating of asthma control after spirometry was also
      collected. Stepwise regression methods were used to select a subset of items that
      showed the greatest discriminant validity in relation to the specialist's rating
      of asthma control. Internal consistency reliability was computed, and
      discriminant validity tests were conducted for ACT scale scores. The performance
      of ACT was investigated by using logistic regression methods and receiver
      operating characteristic analyses. RESULTS: Five items were selected from
      regression analyses. The internal consistency reliability of the 5-item ACT scale
      was 0.84. ACT scale scores discriminated between groups of patients differing in
      the specialist's rating of asthma control (F = 34.5, P <.00001), the need for
      change in patient's therapy (F = 40.3, P <.00001), and percent predicted FEV(1)
      (F = 4.3, P =.0052). As a screening tool, the overall agreement between ACT and
      the specialist's rating ranged from 71% to 78% depending on the cut points used,
      and the area under the receiver operating characteristic curve was 0.77.
      CONCLUSION: Results reinforce the usefulness of a brief, easy to administer,
      patient-based index of asthma control.

PMID- 14713909
TI  - Asthma prevalence and morbidity among rural Iowa schoolchildren.
AB  - BACKGROUND: There are conflicting findings about the prevalence of asthma among
      farm and nonfarm children. OBJECTIVES: We sought to estimate asthma prevalence
      and morbidity and determine differences between farm and nonfarm children.
      METHODS: The study population consisted of all children aged 6 to 14 years
      enrolled in 10 school districts in 2 noncontiguous rural Iowa counties from 2000
      through 2002. The mailed parental screening questionnaire included the
      International Study of Asthma and Allergies in Childhood core questionnaire,
      items from the Functional Severity Index, and items on physician diagnosis and
      medication and urgent care use. RESULTS: The response rate was 86.6%. The 12
      month prevalence of wheeze was 19.1%. Self-reported physician diagnosis of asthma
      was reported by 13.4%. On multivariable analysis controlling for age, sex, and
      county, children who lived on farms were less likely than those who lived in town
      to have ever wheezed (odds ratio, 0.71; 95% CI, 0.58-0.87) or to have wheezed
      during the past year (odds ratio, 0.77; 95% CI, 0.60-0.98). However, this
      protective association with farming was only observed in one of the study
      counties. Among those who wheezed, farm and nonfarm children were equally likely
      to have been given a diagnosis of asthma and had comparable morbidity.
      CONCLUSION: By using a standardized questionnaire with a high response rate in
      this large, rural, population-based study, asthma prevalence rivaled that in
      large Midwestern cities. Unmeasured risk factors might account for the apparent
      protective effect in Keokuk County. These findings cast doubt on a protective
      effect of rural life for the development of childhood asthma.

PMID- 14713910
TI  - Airway glycoprotein secretion parallels production and predicts airway
      obstruction in pulmonary allergy.
AB  - BACKGROUND: Airway obstruction, perhaps the most relevant clinical feature of
      asthma, is typically assessed in allergic asthma models as airway
      hyperresponsiveness. Excess secretion of airway glycoproteins also contributes to
      airway obstruction in asthma but is not measured as part of most experimental
      models. OBJECTIVE: The purposes of this study were to develop a reliable,
      quantitative assay for detecting secreted airway glycoproteins and to assess the
      secretion of airway glycoproteins in comparison with other markers of airway
      obstruction resulting from allergic lung inflammation. METHODS: Two microtiter
      plate-based glycoprotein-detecting methods were developed, one using an
      antiglycoprotein antibody and the other using the glycoprotein-binding plant
      lectin, jacalin. Both methods were used to assess airway glycoprotein secretion
      in response to 2 defined agonists given intranasally, IL-13 and an allergen
      derived from Aspergillus fumigatus. Glycoprotein secretion was assessed
      concomitant with another measure of airway obstruction, airway
      hyperresponsiveness provoked by acetylcholine challenge, and a histologic method
      for quantitating glycoprotein production. RESULTS: Both assays were sufficient
      for quantitating airway glycoproteins over the full range of values encountered
      from murine bronchoalveolar lavage and yielded highly reproducible data.
      Secretion of airway glycoproteins increased commensurate with the detection of
      both airway hyperresponsiveness and airway glycoprotein production induced by IL
      13 and allergen. CONCLUSION: Airway glycoprotein secretion is a consistent
      feature of the allergic lung phenotype and likely contributes to airway
      obstruction induced by allergen in both humans and rodents.

PMID- 14713911
TI  - Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide.
AB  - BACKGROUND: The natriuretic hormone peptide (NHP)(99-126), a C-terminal peptide
      of pro-atrial natriuretic factor (proANF), induces bronchodilatory effects in
      people with asthma. Recently, another plasmid-encoded C-terminal peptide, pNHP(73
      102), was shown to induce a long-lasting bronchoprotective effect in a mouse
      model of allergic asthma. OBJECTIVE: This study was carried out to determine the
      role of lung epithelial cells in the bronchoprotective and anti-inflammatory
      activity of these peptides. METHODS: Human type II alveolar epithelial cells
      (A549) and normal human bronchial epithelial (NHBE) cells were transfected with
      pNHP(73-102) to test the effect of this peptide on activation of these cells.
      After transfection, cells were analyzed for changes in Ca(++) and nitric oxide
      (NO) levels. Also, activation of NFkappaB and the extracellularly regulated
      kinase (ERK) 1, 2 signaling pathway was examined by luciferase reporter assay and
      phosphorylation studies respectively. RESULTS: Analysis of intracellular Ca(++)
      levels in pNHP(73-102) -transfected A549 or NHBE showed that the peptide
      increases release. This Ca(++) release was accompanied by an increase in the
      production of NO. Also, overexpression of pNHP(73-102), but not pVAX control, in
      phorbol myristate acetate-activated A549 cells resulted in a significant decrease
      in expression of a cotransfected nuclear factorkappaB (NFkappaB)-luciferase
      reporter. Similarly, pNHP(73-102) decreased TNF-alpha-induced NFkappaB activation
      in NHBE cells. Furthermore, NHP(73-102) but not atrial natriuretic peptide
      decreased phosphorylation of Erk-1, 2 in A549 cells. CONCLUSIONS: Overexpression
      of pNHP(73-102) in epithelial cells causes increased production of intracellular
      Ca(++) and NO, with a concomitant decrease in activation of NFkappaB and ERK1, 2.
      These results suggest a bronchodilatory and anti-inflammatory activity of this
      peptide.

PMID- 14713912
TI  - Association between asthma and rhinitis according to atopic sensitization in a
      population-based study.
AB  - BACKGROUND: Although asthma and rhinitis often occur together, the reason for
      this common comorbidity is still a matter of debate. OBJECTIVE: We sought to
      assess whether the coexistence of asthma and rhinitis could be explained by
      common risk factors. METHODS: International cross-sectional study of
      representative samples of young adults, who completed a detailed questionnaire
      and underwent lung function tests, bronchoprovocation challenge, IgE
      measurements, and skin prick tests. RESULTS: In all countries, asthma and
      bronchial hyperreactivity were more frequent in subjects with rhinitis than in
      those without (odds ratio [OR], 6.63; 95% CI, 5.44-8.08; and OR, 3.02 95% CI,
      2.66-3.43, respectively). Seventy-four percent to 81% of subjects with asthma
      reported rhinitis, depending on sensitization to specific allergens. Conversely,
      the risk of asthma increased from 2.0% in subjects without rhinitis to 6.7% in
      subjects with rhinitis only when exposed to pollen, 11.9% in subjects with
      rhinitis when exposed to animals, and 18.8% in subjects with rhinitis either when
      exposed to pollen or to animals. The association between rhinitis and asthma
      remained significant after adjustment for total IgE, parental history of asthma,
      and allergen sensitization (OR, 3.41; 95% CI, 2.75-4.2 suggesting that the
      coexistence of asthma and rhinitis is not solely due to atopic predisposition to
      these 2 diseases. CONCLUSIONS: Although there were some variations in the
      association between asthma and rhinitis according to sensitization to individual
      allergens, the strong association between asthma and rhinitis was not fully
      explained by shared risk factors, including atopy. Our findings are consistent
      with the hypothesis that rhinitis might increase the risk of asthma.

PMID- 14713913
TI  - Difficult asthma in children: an analysis of airway inflammation.
AB  - BACKGROUND: Difficult asthma in children displays distinct clinical patterns, and
      its physiopathology remains poorly understood. OBJECTIVE: To determine the
      characteristics of the bronchial inflammatory profile in children with difficult
      asthma. METHODS: We performed endobronchial biopsy and bronchoalveolar lavage in
      28 children with persistent bronchial obstruction despite high doses of inhaled
      corticosteroids and regular treatment with long-acting beta(2)-agonists: 13 had
      persistent symptoms and 15 had few or no symptoms. RESULTS: The number of
      eosinophils (P =.03) and neutrophils (P =.04) in the epithelium was significantly
      higher in symptomatic children than in children with few symptoms. Reticular
      basement membrane thicknening was similar in both groups. IFNgamma levels (P
      =.03) and IFNgamma/IL-4 ratio (P =.01) were significantly higher in children with
      few symptoms. CONCLUSIONS: In symptomatic children, T(H)2-type inflammation was
      associated with the presence of activated eosinophils in the epithelium, whereas
      asthma in children with few symptoms was associated with an increase in T(H)1
      cytokine levels. The high levels of IFNgamma suggest that this T(H)1 cytokine may
      modulate the local inflammatory response.

PMID- 14713914
TI  - Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic
      inflammation.
AB  - BACKGROUND: Asthma is a heterogeneous process, yet little is understood regarding
      phenotypes. OBJECTIVE: To determine whether phenotypic differences exist between
      early-onset, severe asthma as compared with late-onset disease and whether the
      presence or absence of eosinophilia influences the phenotypes. METHODS: Cross
      sectional analysis of integrated clinical, physiologic, and pathologic data
      collected from 80 subjects with severe asthma. Subjects were divided into those
      with asthma onset before age 12 years (n = 50) versus after age 12 (n = 30) and
      by the presence or absence of lung eosinophils. RESULTS: Subjects with early
      onset, severe asthma had significantly more allergen sensitivity (skin test
      positivity, 98% vs 76%, P <.007) and more allergic symptoms (P values all
      <or=.02) than subjects with late-onset asthma. In contrast, subjects with late
      onset asthma had lower lung function (P values =.05 to.07) than early-onset,
      despite a shorter (P <.0001) duration of illness. Both groups had a high degree
      of general asthma symptoms, but those with persistent eosinophils from either age
      at onset group had significantly more (multiple P values <.05). Similarly, the
      presence of eosinophils in either age at onset group was associated with the
      lowest lung function (P <or=.02). Although late-onset asthma was associated with
      the highest numbers of lung eosinophils (P <.007), only early-onset severe asthma
      was associated with a lymphocytic/mast cell inflammatory process. Finally,
      subjects with late-onset asthma without eosinophils had no subepithelial basement
      membrane thickening, suggesting a different pathologic process. CONCLUSIONS:
      Differentiating severe asthma by age at onset and presence or absence of
      eosinophils identifies phenotypes of asthma, which could benefit subsequent
      genetic and therapeutic studies.

PMID- 14713915
TI  - Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban
      housing: month 12 continuation results.
AB  - BACKGROUND: In the first 6 months of this previously published, randomized trial,
      the combined intervention of occupant education, insecticide bait application,
      and professional cleaning significantly reduced cockroach numbers and Bla g 1
      allergen levels in inner-city homes. OBJECTIVE: This continuation study
      investigated whether the cockroach allergen reductions achieved by month 6 could
      be maintained through month 12 with insecticide application alone. METHODS:
      Because we had agreed to place insecticide bait in control homes at the
      conclusion of the first study, intervention and control homes were treated with
      insecticide bait at months 6 and 9. No other intervention was conducted in either
      arm. Vacuumed dust and swab samples were collected at month 12. Twenty-one of the
      31 original homes completed the 12-month study. RESULTS: Among the original
      intervention homes, Bla g 1 concentrations remained essentially unchanged from
      months 6 to 12. However, among the crossed-over control homes, the geometric mean
      Bla g 1 concentrations (Units per gram of dust) decreased from 287 to 14.4 for
      kitchen floors (95% reduction), from 28.8 to 5.6 for living room floors/sofas
      (81% reduction), from 26.7 to 4.7 for bedroom floors (82% reduction), and from
      7.2 to 2.4 for beds (67% reduction). At month 12, Bla g 1 concentrations did not
      significantly differ between intervention and crossed-over control homes (P >.64
      at each location). Similar results were seen for the allergen Bla g 2.
      CONCLUSIONS: Reductions in cockroach allergen concentrations achieved through the
      combined intervention of occupant education, insecticide application, and
      professional cleaning can be maintained with continued cockroach control.
      Surprisingly, and in contrast to other studies, insecticide application alone
      significantly lowered allergen concentrations in the crossed-over control homes.
      This unexpected result is being tested further in another randomized trial.

PMID- 14713916
TI  - Induction of the epidermal growth factor receptor and its ligands in nasal
      epithelium by ozone.
AB  - BACKGROUND: Ozone is a photochemical oxidant pollutant that is an important
      public health hazard. Although the inflammatory response that occurs in response
      to ozone inhalation is well characterized, the mechanisms underlying epithelial
      cell activation are not well understood. OBJECTIVE: Because the epidermal growth
      factor receptor (EGFR) is a central regulator of epithelial function, we tested
      the hypothesis that nasal epithelial cells respond to ozone-induced oxidant
      stress by modulating expression of the EGFR and its ligands, EGF and transforming
      growth factor-alpha (TGF-alpha). METHODS: Normal volunteers were exposed to air
      or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were
      harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF
      alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF
      alpha; mediator release was measured by ELISA and cellular EGFR expression by
      immunoblotting and fluorescence-activated cell sorting analysis. RESULTS:
      Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P
      <.05) increased in the nasal biopsy specimens after ozone exposure, and there was
      a significant positive correlation between EGFR expression and the increase in
      neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro
      exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR
      expression, even though IL-8 release was enhanced. In contrast, exposure to TNF
      alpha caused EGFR levels to increase significantly. CONCLUSION: These data
      suggest that the ozone-induced increase in EGFR expression observed in vivo is
      indirect, perhaps mediated by neutrophil-derived TNF-alpha.

PMID- 14713917
TI  - Sustained increases in numbers of pulmonary dendritic cells after respiratory
      syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in infants can lead
      to wheezing and early allergic sensitization. In mice, RSV infection enhances
      allergic airway inflammation and airway hyperresponsiveness. Dendritic cells are
      critical in inducing T-cell responses to both viruses and allergens and could be
      pivotal in regulating interactions between these. OBJECTIVE: This study addresses
      the effects of RSV infection on phenotype and function of pulmonary dendritic
      cells. METHODS: BALB/c mice were infected with RSV, and expression of CD11c, MHC
      II, and CD86 on lung and spleen cells was monitored by flow cytometry for 21 days
      after infection. CD11c(+) cells were isolated to assess their phagocytic capacity
      and their ability to induce proliferation in allogenic T cells. RESULTS: Numbers
      of pulmonary CD11c(+) MHC II(hi) cells increased 13-fold starting from day 6
      after RSV infection. This was associated with increased CD86 expression, reduced
      phagocytosis, and increased allogenic T-cell stimulatory capacity in CD11c(+)
      cells. These changes in the lung outlasted acute infection and were not observed
      in spleens. CONCLUSION: RSV infection results in sustained increases in numbers
      of mature dendritic cells in the lung. These might well contribute to the
      development of intense airway inflammation and airway hyperresponsiveness after
      RSV infection and to enhancement of subsequent responses to allergen exposure.

PMID- 14713918
TI  - The addition of zafirlukast to cetirizine improves the treatment of chronic
      urticaria in patients with positive autologous serum skin test results.
AB  - BACKGROUND: Because leukotrienes have potent local effects on cutaneous
      vasculature, leukotriene antagonists might be effective in the treatment of
      chronic urticaria. OBJECTIVE: A double-blinded, placebo-controlled trial
      comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a
      day versus cetirizine 10 mg daily and placebo was conducted to determine whether
      subjects with chronic urticaria benefit from add-on therapy with a leukotriene
      modifying agent. METHODS: Patients 12 years or older with a history of chronic
      urticaria (more than 6 weeks in duration) required diary documentation of 6 or
      more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist
      therapy for enrollment. At baseline, all subjects were skin tested to autologous
      serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies.
      Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a
      day and placebo twice daily for 1 week. Those patients with persistent hives were
      randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or
      cetirizine 10 mg daily and placebo. At each successive weekly visit, physician
      and patient treatment effectiveness score (TES) and visual analog scale (VAS)
      ratings were recorded. Statistical analysis used generalizing estimating
      equations to compare the effect of combination therapy versus monotherapy on TES
      and VAS ratings. Results were adjusted for baseline rating, recruiting center,
      and autologous serum skin test (ASST). A separate analysis evaluated patients
      with positive ASST results receiving combination therapy versus monotherapy.
      RESULTS: Combination therapy with zafirlukast demonstrated a modest but
      significantly greater improvement compared with cetirizine monotherapy in
      physician and patient recorded VAS ratings at visit 4 and across treatment visits
      4 through 6 (P <.05 unless stated otherwise). Subjects with ASST positive results
      receiving combination therapy as compared with subjects with negative ASST
      results exhibited a significant improvement in patient recorded VAS ratings
      across visits 4 through 6. Subgroup analysis of subjects with ASST positive
      results receiving combination therapy versus monotherapy showed improvement in
      physician recorded TES at visit 5, physician recorded VAS at visits 4 and 5 and
      across visits 4 through 6, as well as for patient recorded VAS at visit 5. There
      were no significant results for patients with ASST negative results. CONCLUSION:
      The results of this study indicate that only patients with autoimmune (ASST
      positive) chronic urticaria refractory to H(1)-antagonist monotherapy might
      benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast
      to their treatment regimen. These results also suggest that routine screening of
      patients with chronic urticaria with the ASST might be useful in formulating
      therapeutic algorithms in the management of chronic urticaria.

PMID- 14713920
TI  - Recombinant lipid transfer protein Cor a 8 from hazelnut: a new tool for in vitro
      diagnosis of potentially severe hazelnut allergy.
AB  - BACKGROUND: Cor a 1.04 has been identified as the major hazelnut allergen in 65
      European patients with positive double-blind, placebo-controlled food challenge
      results to hazelnut. Recently, the 11S globulin Cor a 9 was shown to be a pollen
      independent hazelnut allergen in the United States, whereas preliminary data
      suggest the lipid transfer protein (LTP) as an important birch pollen-unrelated
      hazelnut allergen in Europe. OBJECTIVE: We sought to recruit a group of European
      patients allergic to hazelnut without birch pollen allergy and to identify and
      clone the major food allergen(s) in this study population. METHODS: We recruited
      26 such Spanish patients, including 10 patients with anaphylaxis. IgE
      immunoblotting was performed with hazelnut extract. Hazelnut LTP Cor a 8 was
      cloned by using a PCR strategy, purified, and subjected to IgE immunoblotting.
      Recombinant Cor a 8, rCor a 1.0401, and rCor a 2 (profilin) were further
      investigated by means of enzyme allergosorbent test. Immunoblot inhibition
      experiments were used to compare the immunologic properties of natural and
      recombinant LTP. RESULTS: A 9-kd major allergen was identified in hazelnut
      extract. Cloning, sequencing, heterologous expression, and inhibition experiments
      identified it as an LTP. The prevalence of specific IgE antibody reactivity to
      LTP was 62% in hazelnut extract and 77% when recombinant LTP was tested by means
      of immunoblotting. IgE immunoblot inhibition with hazelnut extract showed that
      natural Cor a 8 and rCor a 8 shared identical epitopes. Only one patient had
      positive reactivity to Cor a 1.04, and no patients had positive reactivity to Cor
      a 2. Two sera bound to high-molecular-weight allergens. The LTP was denominated
      as Cor a 8 and submitted to the allergen database of the World Health
      Organization/International Union of Immunological Societies Allergen Nomenclature
      Subcommittee. CONCLUSIONS: Cor a 8 is a relevant allergen for a majority of
      Spanish patients with hazelnut allergy that can cause severe allergic reactions.

PMID- 14713921
TI  - Soybean allergy in patients allergic to birch pollen: clinical investigation and
      molecular characterization of allergens.
AB  - BACKGROUND: Allergic reactions to legumes are generally thought to be acquired by
      means of primary sensitization through the gastrointestinal tract. Recently, Gly
      m 4 (starvation-associated message 22), a Bet v 1-related pathogenesis-related
      protein 10 from soy, was suggested to be an allergen in patients with allergic
      reactions to a dietary product containing a soy protein isolate. OBJECTIVE: We
      sought to evaluate the clinical relevance of Gly m 4 in subjects allergic to
      birch pollen with soy allergy and to assess the risk for subjects allergic to
      birch pollen to acquire soy allergy. METHODS: Twenty-two patients allergic to
      birch pollen with soy allergy confirmed by means of positive double-blind,
      placebo-controlled food challenge results (n = 16) or a convincing history (n =
      6) were investigated for IgE reactivity to birch pollen and soy allergens by
      using the Pharmacia CAP system and immunoblot analysis. Cross-reactivity was
      assessed by means of enzyme allergosorbent test inhibition. Ninety-four patients
      with birch pollen allergy were interviewed to assess soy tolerance and screened
      for IgE reactivity to Gly m 4 by means of immunoblotting. The Gly m 4 content in
      soy foods and soybean varieties was investigated by means of quantitative
      evaluation of immunoblots. RESULTS: During double-blind, placebo-controlled food
      challenge, 10 patients experienced symptoms localized to the oral cavity, and 6
      patients had a more severe reaction. CAP analysis revealed Gly m 4-specific IgE
      in 96% (21/22) of the patients. All patients had Bet v 1-specific IgE antibodies,
      and 23% (5/22) had positive Bet v 2 results. In IgE immunoblotting 25% (6/22) of
      the patients recognized soy profilin (Gly m 3), and 64% (14/22) recognized other
      soy proteins. IgE binding to soy was at least 80% inhibited by birch pollen and
      60% inhibited by rGly m 4 in 9 of 11 sera tested. Seventy-one percent (67/94) of
      highly Bet v 1-sensitized patients with birch pollen allergy were sensitized to
      Gly m 4, and 9 (9.6%) of those patients reported soy allergy. The Gly m 4 content
      in soy products ranged between 0 and 70 ppm (milligrams per kilogram).
      CONCLUSIONS: Our results confirm that soybean is another birch pollen-related
      allergenic food. Gly m 4 is the major soy allergen for patients allergic to birch
      pollen with soy allergy. The content of Gly m 4 in soy food products strongly
      depends on the degree of food processing.

PMID- 14713922
TI  - Detection of specific IgE to quinolones.
AB  - BACKGROUND: In the last years, immediate reactions to quinolone antibiotics have
      been observed with increasing frequency, mainly urticaria, angioedema, and shock.
      No test was available because of the high incidence of false-positive results on
      skin tests. Thus the pathogenesis, value of diagnostic procedures, and cross
      reactivity have not been evaluated in a systematic way. OBJECTIVE: We sought to
      assess whether these reactions are IgE mediated and whether an in vitro test for
      quinolone-specific IgE is useful in the diagnosis and understanding of cross
      reactivity. METHODS: We assayed specific serum IgE to quinolones using epoxy
      activated sepharose 6B as the solid phase in 55 patients with immediate adverse
      reactions; specificity of IgE binding was demonstrated by inhibition tests.
      RESULTS: The test yielded positive results in 30 (54.5%) patients who were tested
      1 to 48 months after the reaction had occurred. The quinolone-specific IgE seems
      to disappear more slowly in atopic patients. The cross-reactivity between various
      quinolones allowed us to identify a common structural motif within quinolones
      that might be responsible for clinical and serologic cross-reactivity.
      CONCLUSION: A substantial portion of immediate reactions to quinolones appear to
      be IgE mediated. Cross-reactivity of IgE among different quinolones is frequent
      and suggests that a common avoidance of quinolones should be attempted in all
      patients with respective symptoms.

PMID- 14713924
TI  - Interpregnancy interval might affect the risk of childhood atopy.

PMID- 14713923
TI  - Identification and immunologic characterization of an allergen, alliin lyase,
      from garlic (Allium sativum).
AB  - BACKGROUND: Garlic (Allium sativum) is one of the most common relishes used in
      cooking worldwide. Very few garlic allergens have been reported, and garlic
      allergy has been rarely studied. OBJECTIVE: The aim of the study was to identify
      allergenic proteins in garlic and to investigate their importance in allergies to
      other Allium species (leek, shallot, and onion). METHODS: A crude extract of
      garlic proteins was separated by SDS-PAGE and 2-dimensional electrophoresis;
      immunoblotting was then performed with the use of individual and pooled sera from
      patients with garlic allergy, and the major IgE-binding proteins were analyzed by
      amino acid sequencing and mass spectrometry. The putative allergens were further
      purified by chromatography; the antigenicity, allergenicity, and IgE-binding
      cross-reactivity of the purified protein were then studied by immunoblotting,
      periodate oxidation, skin tests, and IgE-binding inhibition assays. RESULTS: A
      major allergen, alliin lyase, was identified by mass spectrometry and Edman
      sequencing and purified to homogeneity through the use of a simple 2-step
      chromatographic method. Skin tests showed that the purified protein elicited IgE
      mediated hypersensitive responses in patients with garlic allergy. Periodate
      oxidation showed that carbohydrate groups were involved in the antigenicity,
      allergenicity, and cross-reactivity. Garlic alliin lyase showed strong cross
      reactivity with alliin lyases from other Allium species, namely leek, shallot,
      and onion. CONCLUSIONS: Alliin lyase was found to be a major garlic allergen in a
      garlic-allergic group of patients in Taiwan. The wide distribution of alliin
      lyase in Allium suggests it may be a new cross-reactive allergen.

PMID- 14713925
TI  - Allergy to eggplant (Solanum melongena).

PMID- 14713926
TI  - Lack of cross-reactivity to meropenem in a patient with an allergy to imipenem
      cilastatin.

PMID- 14713927
TI  - Different patterns of allergen recognition in children allergic to orange.

PMID- 14713929
TI  - Enhanced synergy between fluticasone propionate and salmeterol inhaled from a
      single inhaler versus separate inhalers.

PMID- 14713930
TI  - Results of the US Third National Health and Nutrition Examination Survey support
      the hygiene hypothesis.

PMID- 14713932
TI  - Negative venom skin test results and mastocytosis.

PMID- 14713933
TI  - Eosinophils in allergic inflammation.

PMID- 14713937
TI  - Providing the clinical basis for new interventional therapies: refined diagnosis
      and assessment of recovery after spinal cord injury.
AB  - Today, there is accumulating evidence from animal experiments that axonal
      regeneration and an enhanced level of functional repair can be induced after a
      spinal cord injury (SCI). Consequently, in the near future, new therapeutic
      approaches will be developed for the treatment of patients with SCI. The aim of
      the project presented here is to provide the required clinical basis for the
      implementation of novel interventional therapies. Refined and combined clinical
      and neurophysiological measures are needed for a precise qualitative and
      quantitative assessment of spinal cord function in patients with SCI at an early
      stage. This represents a basic requirement to recognise any improvement in the
      recovery of function and to monitor any significant effect of a new treatment. To
      this aim, five European Spinal Cord Injury Centres involved in the rehabilitation
      of acute SCI patients have built up a close clinical collaboration to develop a
      standardised protocol for the assessment of the outcome after SCI and the extent
      of recovery achieved by actually applied therapies in a larger population of SCI
      patients. The project's aim is to establish objective, refined tools as a basis
      for monitoring the effects of new treatment strategies.

PMID- 14713938
TI  - Calculus anuria in a spina bifida patient, who had solitary functioning kidney
      and recurrent renal calculi.
AB  - STUDY DESIGN: Clinical case report with comments by colleagues from Austria,
      Belgium, Germany, Japan, and Poland. OBJECTIVES: To discuss challenges in the
      management of spinal bifida patients, who have marked kyphoscoliosis and no
      vascular access. SETTING: Regional Spinal Injuries Centre, Southport, UK.
      METHODS: A female patient, who was born with spina bifida, paraplegia and
      solitary right kidney, had undergone ileal loop urinary diversion. Renal calculi
      were noted in 1986. Percutaneous nephrostolithotomy was performed in 1989 and
      there was no residual stone fragment. However, she developed recurrence of
      calculi in the lower pole of the right kidney in 1991. Intravenous urography,
      performed in 1995, revealed right staghorn calculus and hydronephrosis. Chest X
      ray showed markedly restricted lung volume due to severe kyphoscoliosis. In 2000,
      she was declared unsuitable for anaesthesia due to a lack of venous access and a
      high likelihood of difficulty in weaning off the ventilator in the postoperative
      period. In June 2002, she developed anuria (urine output=18 ml/24 h) due to ball
      valve-type obstruction by a renal stone at the ureteropelvic junction. Urea: 14.4
      mmol/l; creatinine: 236 microl/l. Ultrasound showed right hydronephrosis.
      Percutaneous nephrostomy was performed. RESULTS: Following relief of urinary
      tract obstruction, there was postobstructive diuresis (3765 ml/24 h). However,
      the patient expired 19 days later due to progressive respiratory failure.
      CONCLUSION: In this spina bifida patient, who had reached the age of 35 years,
      severe kyphoscoliosis and lack of vascular access presented insurmountable
      challenges to implement the desired surgical procedure for removal of stones from
      a solitary kidney.

PMID- 14713939
TI  - Muscle activation during unilateral stepping occurs in the nonstepping limb of
      humans with clinically complete spinal cord injury.
AB  - STUDY DESIGN: Comparison of different kinematic and loading conditions on muscle
      activation in clinically complete spinal cord-injured subjects stepping
      unilaterally with manual assistance. OBJECTIVE: To determine if rhythmic lower
      limb loading or movement could produce rhythmic muscle activation in the
      nonstepping limb of subjects with clinically complete spinal cord injury (SCI).
      SETTING: Human Locomotion Research Center, Department of Neurology, University of
      California, Los Angeles, USA. METHODS: We recorded electromyography, joint
      kinematics, and vertical ground reaction forces as four subjects with clinically
      complete SCI stepped with manual assistance and partial bodyweight support. For
      all trials, one limb continuously stepped while the other limb underwent
      different conditions, including rhythmic lower limb loading in an extended
      position without limb movement, rhythmic lower limb movement similar to stepping
      without limb loading, and no lower limb loading or movement with the leg in an
      extended or flexed position. RESULTS: Three subjects displayed rhythmic muscle
      activity in the nonstepping limb for trials with rhythmic limb loading, but no
      limb movement. One subject displayed rhythmic muscle activity in the nonstepping
      limb for trials without ipsilateral limb loading or movement. The rhythmic muscle
      activity in the nonstepping limb was similar to the rhythmic muscle activity
      during bilateral stepping. CONCLUSIONS: The human spinal cord can use sensory
      information about ipsilateral limb loading to increase muscle activation even
      when there is no limb movement. The results also indicate that movement and
      loading in one limb can produce rhythmic muscle activity in the other limb even
      when it is stationary and unloaded. These findings emphasize the importance of
      optimizing load-related and contralateral sensory input during gait
      rehabilitation after SCI.

PMID- 14713940
TI  - Fat oxidation at different intensities in wheelchair racing.
AB  - STUDY DESIGN: Determination of fat oxidation at three different intensities in
      trained wheelchair athletes on the treadmill. OBJECTIVE: The aim of the study was
      to assess the level and highest rate of fat oxidation in endurance-trained
      wheelchair athletes for recommendation on endurance training. SETTING: Institute
      of Sports Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland. METHODS: Nine
      (seven men and two women) endurance-trained wheelchair athletes (VO(2peak) 40.2+/
      6.7 ml/kg/min) were studied over 20 min at 55, 65 and 75% VO(2peak) on a
      treadmill in their own racing wheelchairs in order to find the exercise intensity
      with the highest absolute fat oxidation. RESULTS: As presumed, total energy
      expenditure for wheelchair racing was highest at 75% VO(2peak), while absolute
      fat oxidation was statistically not significantly different at the three tested
      intensities. Percentage of energy expenditure from fat oxidation decreased with
      increasing intensity from 31.4% at 55% VO(2peak) to 20.9% at 75% VO(2peak), while
      percentage from carbohydrate oxidation increased from 68.6% at 55% VO(2peak) to
      79.1% at 75% VO(2peak). CONCLUSION: For wheelchair athletes, we recommend
      training of fat metabolism for endurance exercise at an intensity of 55%
      VO(2peak), because absolute fat metabolism is not higher at higher intensities
      but less carbohydrates are used at lower intensity levels. At lower intensities,
      exercise can be performed over a longer time before the emptied glycogen stores
      will limit exercise duration. This may apply especially to paraplegic subjects
      whose active muscle mass is limited in contrast to able-bodied athletes.

PMID- 14713941
TI  - Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells
      following spinal cord injury in rat.
AB  - STUDY DESIGN: A standardized animal model of contusive spinal cord injury (SCI)
      with incomplete paraplegia was used to test the hypothesis that moderate systemic
      hypothermia reduces neural cell death. Terminal deoxynucleotidyl transferase
      [TdT]-mediated deoxyuridine triphosphate [dUTP] nick-end labeling (TUNEL)
      staining was used as a marker of apoptosis or cell damage. OBJECTIVE: To
      determine whether or not moderate hypothermia could have a neuroprotective effect
      in neural cell death following spinal cord injury in rats. SETTING: Kagawa
      Medical University, Japan. METHODS: Male Sprague-Dawley (SD) rats (n=39) weighing
      on average 300 g (280-320 g) were used to prepare SCI models. After receiving
      contusive injury at T11/12, rats were killed at 24 h, 72 h, or 7 days after
      injury. The spinal cord was removed en bloc and of examined at five segments: 5
      and 10 mm rostral to the center of injury, center of injury, and 5 and 10 mm
      caudal to the center of injury. Rats that received hypothermia (32 degrees C/4 h)
      were killed at the same time points as those that received normothermia (37
      degrees C/3 h). The specimens were stained with hematoxylin and eosin, and
      subjected to in situ nick-end labeling (TUNEL), a specific method for visualizing
      cell death in the spinal cord. RESULTS: At 24 h postinjury, TUNEL positive cells
      (TPC) decreased significantly 10 mm rostral to center of injury in hypothermic
      animals compared to the normothermia group. At 72 h post-SCI, TPC also decreased
      significantly at 5 mm rostral, and 5 and 10 mm caudal to the lesion center
      compared to normothermic animals. At 7 days postinjury, a significant decrease of
      TPC was observed at the 5 mm rostral and 5 mm caudal sites compared to
      normothermic animals. CONCLUSION: These results indicate that systemic
      hypothermia has a neuroprotective effect following SCI by attenuating post
      traumatic TPC.

PMID- 14713942
TI  - Gross quantitative measurements of spinal cord segments in human.
AB  - STUDY DESIGN: Anatomical measurement. OBJECTIVE: To obtain quantitative
      anatomical data on each spinal cord segment in human, and determine the presence
      of correlations between the measures. SETTING: Department of Rehabilitation
      Medicine, Pusan National University Hospital, Pusan, Korea. METHODS: A total of
      15 embalmed Korean adult human cadavers (13 males, two females; mean age 57.3
      years) were used. The length of each cord segment was defined as the root
      attachment length plus the upper inter-root length. After performing a total
      vertebrectomy, a transverse cut was made at the approximate proximal and distal
      point of each segment from segment C3 to S5. Sagittal and transverse diameters at
      the proximal end of each segment, and cross-sectional area, height, and volume of
      the segment were measured. RESULTS: The transverse diameter was largest at
      segment C5, and decreased progressively to segment T8. However, the sagittal
      diameter of each segment did not change distinctly with the segment. The cervical
      and lumbar enlargements were determined by the transverse diameters of the
      segments. Segment C5 had the largest cross-sectional area, at 75.0 mm(2). Segment
      T6 was the longest, averaging 22.4 mm in length. The longest segment in the
      cervical spinal cord was segment C5, at 15.5 mm, and segment L1 in the lumbar
      spinal cord. The volume was largest at segment C5, with a value of 1173.9 mm(3).
      CONCLUSIONS: We found characteristic quantitative differences in the values of
      the parameters measured in the thoracic spinal cord compared to those measured in
      the cervical and lumbar or lumbosacral spinal cords. These measurements of spinal
      cord segments appear to provide valuable and practical standard quantitative
      features and may provide basic data for understanding the morphometric
      characteristics relevant to pathophysiologic conditions of the spinal cord.

PMID- 14713943
TI  - Shoulder pain and its consequences in paraplegic spinal cord-injured, wheelchair
      users.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To describe the consequences of
      shoulder pain on activity and participation in spinal cord-injured paraplegic
      wheelchair users. To describe the prevalence and type of shoulder pain. SETTING:
      Two spinal cord injury (SCI) centres in Sweden. METHODS: All subjects with
      paraplegia due to an SCI of more than 1 year living in the counties of Uppsala
      and Linkoping, Sweden were contacted by mail and asked to fill in a questionnaire
      (89 subjects). Those of the responding 56 subjects with current shoulder pain
      were asked to participate in further examination and interviews. A
      physiotherapist examined 13 subjects with shoulder pain in order to describe type
      and site of impairment. To describe consequences of shoulder pain on activity and
      participation, the Constant Murley Scale (CMS), the Wheelchair Users Shoulder
      Pain Index (WUSPI) the Klein & Bell adl-index and the Canadian Occupational
      Performance Measure (COPM) were used. RESULTS: Out of all respondents, 21 had
      shoulder pain (37.5%). Data from 13 of those subjects were used in the
      description of type and consequences of shoulder pain. Findings of muscular
      atrophy, pain, impingement and tendinits were described. We found no difference
      in ADL-performance with, respectively without, shoulder pain (P=0.08) using the
      Klein & Bell adl-index. No correlation was found between the various descriptions
      of impairment, activity limitations and participation restriction (P>0.08). All
      together 52 problems with occupational performance due to shoulder pain were
      identified using the COPM. Of these, 54% were related to self-care activities.
      CONCLUSION: The consequences of shoulder pain in paraplegic wheelchair users are
      mostly related to wheelchair activities. Since the wheelchair use itself
      presumably cause shoulder problems, this will become a vicious circle. More
      research is needed in order to reduce shoulder problems in wheelchair users.

PMID- 14713944
TI  - Does the neuronal plasticity exist in elderly patients? report of an unusual
      clinical case.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report complete recovery after
      paraplegia in an elderly patient after removal of meningioma at C7-T1 level.
      SETTING: Department of Neurosurgery, Reggio Calabria, Italy. METHODS: An 82-year
      old lady with 48 months of progressive weakness and numbness was admitted with
      complete paraplegia lasting 15 days. Investigations (magnetic resonance imaging
      (MRI)) demonstrated a meningioma at C7-T1. The tumour compressed the extremely
      thinned spinal cord. MRI after surgery showed no evidence of residual tumour and
      the spinal cord was of normal dimensions. The patient recovered fully and
      locomotion was restored. CONCLUSION: Surgical decompression gave an excellent
      result. The result raises the possibility of neuronal plasticity.

PMID- 14713945
TI  - Efficacy of intrathecal morphine in the treatment of baclofen tolerance in a
      patient on intrathecal baclofen therapy (ITB).
AB  - STUDY DESIGN: Case report. OBJECTIVES: A case report of tolerance to intrathecal
      baclofen therapy (ITB) treated with intrathecal morphine ('baclofen holiday').
      SETTING: Institut Guttmann, Neurorehabilitation Hospital of Barcelona, Spain.
      CASE REPORT: A 30-year-old female patient is described with incomplete paraplegia
      below T6 on the left side and below T8 on the right side, ASIA B, caused by
      trauma occurring 12 years previously, in whom an intrathecal system had been
      implanted for baclofen infusion 10 years ago. The patient showed tolerance to
      baclofen therapy and was treated with intrathecal morphine infusion for 2 weeks.
      Baclofen infusion resulted in adequate control of spasticity.

PMID- 14713946
TI  - Intradural disc mimicking: a spinal tumor lesion.
AB  - STUDY DESIGN: A case report of intradural disc hernia mimicking an intradural
      extramedullary spinal tumor lesion in radiological evaluation. OBJECTIVE: To
      describe a lumbar intradural disc herniation with atypical radiological
      appearance and point out the role of contrast magnetic resonance imaging (MRI) of
      the lumbar spine. SETTING: Turkey. CASE REPORT: A 58-year-old man with suspected
      lumbar intradural mass and neurological involvement received L5 total
      laminectomy. L5 total laminectomy was performed, and on inspection dura was
      swollen and immobile. A longitudinal incision was made in the dura and an
      intradural-free disc fragment was removed. The patient's postoperative period was
      uneventful and he had full recovery in 3 months. CONCLUSIONS: Lumbar intradural
      disc rupture must be considered in the differential diagnosis of mass lesions
      causing nerve root or cauda equina syndromes. Contrast-enhanced MRI scans are
      useful to differentiate a herniated disc from a disc space infection or tumor.
      This case demonstrates the role and the importance of contrast MRI in the
      diagnosis of intradural disc herniation.

PMID- 14713947
TI  - Professor Heinrich Sebastian Frenkel: a forgotten founder of rehabilitation
      medicine.
AB  - Frenkel was born and later on practiced medicine in Heiden, Swizerland. This
      small town became, by his vigilant and innovative work, a place of pilgrimage for
      neurologists. He was the first to introduce the concept of exercise to restore
      dexterity and to improve ambulation and so pioneered the specialty of physical
      medicine and rehabilitation. Frenkel's method and philosophy became the
      foundation of treatment for many chronic neurological disabling diseases. His
      personality and work influenced many famous neurologists, worldwide.

PMID- 14713948
TI  - Milk of calcium in urethral diverticulum in a male patient with paraplegia and
      suprapubic urinary drainage.

PMID- 14713949
TI  - Cytoprotection by pre-emptive conditional phosphorylation of translation
      initiation factor 2.
AB  - Transient phosphorylation of the alpha-subunit of translation initiation factor 2
      (eIF2alpha) represses translation and activates select gene expression under
      diverse stressful conditions. Defects in the eIF2alpha phosphorylation-dependent
      integrated stress response impair resistance to accumulation of malfolded
      proteins in the endoplasmic reticulum (ER stress), to oxidative stress and to
      nutrient deprivations. To study the hypothesized protective role of eIF2alpha
      phosphorylation in isolation of parallel stress signaling pathways, we fused the
      kinase domain of pancreatic endoplasmic reticulum kinase (PERK), an ER stress
      inducible eIF2alpha kinase that is normally activated by dimerization, to a
      protein module that binds a small dimerizer molecule. The activity of this
      artificial eIF2alpha kinase, Fv2E-PERK, is subordinate to the dimerizer and is
      uncoupled from upstream stress signaling. Fv2E-PERK activation enhanced the
      expression of numerous stress-induced genes and protected cells from the lethal
      effects of oxidants, peroxynitrite donors and ER stress. Our findings indicate
      that eIF2alpha phosphorylation can initiate signaling in a cytoprotective gene
      expression pathway independently of other parallel stress-induced signals and
      that activation of this pathway can single-handedly promote a stress-resistant
      preconditioned state.

PMID- 14713950
TI  - Hematopoietic, angiogenic and eye defects in Meis1 mutant animals.
AB  - Meis1 and Hoxa9 expression is upregulated by retroviral integration in murine
      myeloid leukemias and in human leukemias carrying MLL translocations. Both genes
      also cooperate to induce leukemia in a mouse leukemia acceleration assay, which
      can be explained, in part, by their physical interaction with each other as well
      as the PBX family of homeodomain proteins. Here we show that Meis1-deficient
      embryos have partially duplicated retinas and smaller lenses than normal. They
      also fail to produce megakaryocytes, display extensive hemorrhaging, and die by
      embryonic day 14.5. In addition, Meis1-deficient embryos lack well-formed
      capillaries, although larger blood vessels are normal. Definitive myeloerythroid
      lineages are present in the mutant embryos, but the total numbers of colony
      forming cells are dramatically reduced. Mutant fetal liver cells also fail to
      radioprotect lethally irradiated animals and they compete poorly in repopulation
      assays even though they can repopulate all hematopoietic lineages. These and
      other studies showing that Meis1 is expressed at high levels in hematopoietic
      stem cells (HSCs) suggest that Meis1 may also be required for the
      proliferation/self-renewal of the HSC.

PMID- 14713951
TI  - Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is
      cell-type-specific.
AB  - Inactivation of the tumor suppressor Rb in the mouse induces cell death, which
      depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on
      Apaf1/Ced4, an apoptosomal factor thought to be required for processing
      procaspase-9 following mitochondrial permeabilization. Here, we report that in
      response to cytotoxic drugs, Apaf1(-/-) primary myoblasts but not fibroblasts
      undergo bona fide apoptosis. Cell demise was associated with disruption of
      mitochondria but not endoplasmic reticulum. Processing of procaspase-9 occurred
      in Apaf1(-/-) myoblasts but not fibroblasts, and ablation of Casp9 prevented drug
      induced apoptosis in both cell types. Deregulation of the Rb pathway by
      overexpression of E2F1 also induced caspase-9-dependent, Apaf1-independent
      apoptosis in myoblasts. Despite its requirement for apoptosis in vitro, mutation
      in Casp9 abrogated cell death in the nervous system and lens but only partly in
      skeletal muscles of Rb-deficient embryos. In addition, developmental cell death
      in fetal liver and PNS was not inhibited in Casp9(-/-) embryos. Therefore, loss
      of pRb elicits apoptosome-dependent and apoptosome-independent cell death, and
      the requirement and coupling of caspase-9 to Apaf1 are both context-dependent.

PMID- 14713952
TI  - Ubiquitination and translocation of TRAF2 is required for activation of JNK but
      not of p38 or NF-kappaB.
AB  - TRAF2 is a RING finger protein that regulates the cellular response to stress and
      cytokines by controlling JNK, p38 and NF-kappaB signaling cascades. Here, we
      demonstrate that TRAF2 ubiquitination is required for TNFalpha-induced activation
      of JNK but not of p38 or NF-kappaB. Intact RING and zinc finger domains are
      required for TNFalpha-induced TRAF2 ubiquitination, which is also dependent on
      Ubc13. TRAF2 ubiquitination coincides with its translocation to the insoluble
      cellular fraction, resulting in selective activation of JNK. Inhibition of Ubc13
      expression by RNAi resulted in inhibition of TNFalpha-induced TRAF2 translocation
      and impaired activation of JNK but not of IKK or p38. TRAF2 aggregates in the
      cytoplasm, as seen in Hodgkin-Reed-Sternberg lymphoma cells, resulting in
      constitutive NF-kappaB activity but failure to activate JNK. These findings
      demonstrate that the TRAF2 RING is required for Ubc13-dependent ubiquitination,
      resulting in translocation of TRAF2 to an insoluble fraction and activation of
      JNK, but not of p38 or NF-kappaB. Altogether, our findings highlight a novel
      mechanism of TRAF2-dependent activation of diverse signaling cascades that is
      impaired in Hodgkin-Reed-Sternberg cells.

PMID- 14713953
TI  - Akt negatively regulates the in vitro lifespan of human endothelial cells via a
      p53/p21-dependent pathway.
AB  - The signaling pathway of insulin/insulin-like growth factor
      1/phosphatidylinositol-3 kinase/Akt is known to regulate longevity as well as
      resistance to oxidative stress in the nematode Caenorhabditis elegans. This
      regulatory process involves the activity of DAF-16, a forkhead transcription
      factor. Although reduction-of-function mutations in components of this pathway
      have been shown to extend the lifespan in organisms ranging from yeast to mice,
      activation of Akt has been reported to promote proliferation and survival of
      mammalian cells. Here we show that Akt activity increases along with cellular
      senescence and that inhibition of Akt extends the lifespan of primary cultured
      human endothelial cells. Constitutive activation of Akt promotes senescence-like
      arrest of cell growth via a p53/p21-dependent pathway, and inhibition of forkhead
      transcription factor FOXO3a by Akt is essential for this growth arrest to occur.
      FOXO3a influences p53 activity by regulating the level of reactive oxygen
      species. These findings reveal a novel role of Akt in regulating the cellular
      lifespan and suggest that the mechanism of longevity is conserved in primary
      cultured human cells and that Akt-induced senescence may be involved in vascular
      pathophysiology.

PMID- 14713955
TI  - Neurodegeneration and energy metabolism: from chemistry to clinics.

PMID- 14713954
TI  - Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron
      RNA.
AB  - Communication between U1 and U2 snRNPs is critical during pre-spliceosome
      assembly; yet, direct connections have not been observed. To investigate this
      assembly step, we focused on Prp5, an RNA-dependent ATPase of the DExD/H family.
      We identified homologs of Saccharomyces cerevisiae Prp5 in humans (hPrp5) and
      Schizosaccharomyces pombe (SpPrp5), and investigated their interactions and
      function. Depletion and reconstitution of SpPrp5 from extracts demonstrate that
      ATP binding and hydrolysis by Prp5 are required for pre-spliceosome complex A
      formation. hPrp5 and SpPrp5 are each physically associated with both U1 and U2
      snRNPs; Prp5 contains distinct U1- and U2-interacting domains that are required
      for pre-spliceosome assembly; and, we observe a Prp5-associated U1/U2 complex in
      S. pombe. Together, these data are consistent with Prp5 being a bridge between U1
      and U2 snRNPs at the time of pre-spliceosome formation.

PMID- 14713956
TI  - Apoptosis to necrosis switching downstream of apoptosome formation requires
      inhibition of both glycolysis and oxidative phosphorylation in a BCL-X(L)- and
      PKB/AKT-independent fashion.
AB  - Human T-lymphoma Jurkat cells treated with several intrinsic death stimuli
      readily undergo a stepwise apoptotic program. Treatment with 1,9-dideoxyforskolin
      (ddFSK), an inactive analogue of the adenylate cyclase activator forskolin,
      induces necrotic cell death and switches to necrosis the response to the
      apoptosis inducers in Jurkat and in other cell models. Yet, in the presence of
      ddFSK, mitochondrial changes are enhanced and apoptosome formation takes place.
      We show that ddFSK does not inhibit the catabolic steps of apoptosis, but rather
      elicits a profound ATP depletion that in turn tunes the mode of cell demise
      towards necrosis. Treatment with ddFSK impairs both glycolysis and oxidative
      phosphorylation in a Bcl-X(L)- and PKB/Akt-independent fashion, and inhibition of
      both processes is needed to affect apoptosis progression. Apoptosis is not
      blocked per se by ATP depletion, as engagement of the Fas receptor directly
      activates caspases, thus bypassing ddFSK inhibition.

PMID- 14713957
TI  - Reactive oxygen species regulate quiescent T-cell apoptosis via the BH3-only
      proapoptotic protein BIM.
AB  - The survival of quiescent T cells in the peripheral immune system is dependent on
      signals transmitted from the extracellular environment. The requirement for
      survival factors is also manifested in vitro, providing a robust system to
      examine molecular mechanisms underlying T-cell death. We show that peripheral T
      cells cultured in the absence of survival factors accumulate reactive oxygen
      species (ROS), upregulate BIM (Bcl-2-interacting mediator of death) and inducible
      nitric oxide synthase (iNOS) expression, culminating in Fas-independent neglect
      induced death (NID). We have examined ROS, iNOS and cytokine modulation of T-cell
      NID. Antioxidants inhibit BIM induction, caspase activation and apoptosis but do
      not promote cell cycle entry. iNOS-deficient T cells are protected from
      apoptosis, implicating iNOS in the regulation of NID via suppression of Bcl-x(L)
      expression and consequent inhibition of BIM activity. Finally, we show that the
      prosurvival cytokine IL-7 elevates Bcl-x(L) expression and transcriptionally
      regulates iNOS but not BIM expression in T cells.

PMID- 14713958
TI  - Specific caspase interactions and amplification are involved in selective
      neuronal vulnerability in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative
      disorder resulting in selective neuronal loss and dysfunction in the striatum and
      cortex. The molecular pathways leading to the selectivity of neuronal cell death
      in HD are poorly understood. Proteolytic processing of full-length mutant
      huntingtin (Htt) and subsequent events may play an important role in the
      selective neuronal cell death found in this disease. Despite the identification
      of Htt as a substrate for caspases, it is not known which caspase(s) cleaves Htt
      in vivo or whether regional expression of caspases contribute to selective
      neuronal cells loss. Here, we evaluate whether specific caspases are involved in
      cell death induced by mutant Htt and if this correlates with our recent finding
      that Htt is cleaved in vivo at the caspase consensus site 552. We find that
      caspase-2 cleaves Htt selectively at amino acid 552. Further, Htt recruits
      caspase-2 into an apoptosome-like complex. Binding of caspase-2 to Htt is
      polyglutamine repeat-length dependent, and therefore may serve as a critical
      initiation step in HD cell death. This hypothesis is supported by the requirement
      of caspase-2 for the death of mouse primary striatal cells derived from HD
      transgenic mice expressing full-length Htt (YAC72). Expression of catalytically
      inactive (dominant-negative) forms of caspase-2, caspase-7, and to some extent
      caspase-6, reduced the cell death of YAC72 primary striatal cells, while the
      catalytically inactive forms of caspase-3, -8, and -9 did not. Histological
      analysis of post-mortem human brain tissue and YAC72 mice revealed activation of
      caspases and enhanced caspase-2 immunoreactivity in medium spiny neurons of the
      striatum and the cortical projection neurons when compared to controls. Further,
      upregulation of caspase-2 correlates directly with decreased levels of brain
      derived neurotrophic factor in the cortex and striatum of 3-month YAC72
      transgenic mice and therefore suggests that these changes are early events in HD
      pathogenesis. These data support the involvement of caspase-2 in the selective
      neuronal cell death associated with HD in the striatum and cortex.

PMID- 14713959
TI  - Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma
      cells.
AB  - Autophagy is originally named as a process of protein recycling. It begins with
      sequestering cytoplasmic organelles in a membrane vacuole called autophagosome.
      Autophagosomes then fuse with lysosomes, where the materials inside are degraded
      and recycled. To date, however, little is known about the role of autophagy in
      cancer therapy. In this study, we present that temozolomide (TMZ), a new
      alkylating agent, inhibited the viability of malignant glioma cells in a dose
      dependent manner and induced G2/M arrest. At a clinically achievable dose (100
      microM), TMZ induced autophagy, but not apoptosis in malignant glioma cells.
      After the treatment with TMZ, microtubule-associated protein light-chain 3 (LC3),
      a mammalian homologue of Apg8p/Aut7p essential for amino-acid starvation-induced
      autophagy in yeast, was recruited on autophagosome membranes. When autophagy was
      prevented at an early stage by 3-methyladenine, a phosphatidylinositol 3
      phosphate kinase inhibitor, not only the characteristic pattern of LC3
      localization, but also the antitumor effect of TMZ was suppressed. On the other
      hand, bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, that
      prevents autophagy at a late stage by inhibiting fusion between autophagosomes
      and lysosomes, sensitized tumor cells to TMZ by inducing apoptosis through
      activation of caspase-3 with mitochondrial and lysosomal membrane
      permeabilization, while LC3 localization pattern stayed the same. These results
      indicate that TMZ induces autophagy in malignant glioma cells. Application of an
      autophagy inhibitor that works after the association of LC3 with autophagosome
      membrane, such as bafilomycin A1, is expected to enhance the cytotoxicity of TMZ
      for malignant gliomas.

PMID- 14713960
TI  - Catalytic activity of caspase-3 is required for its degradation: stabilization of
      the active complex by synthetic inhibitors.
AB  - The activation of caspase-3 represents a critical step in the pathways leading to
      the biochemical and morphological changes that underlie apoptosis. Upon induction
      of apoptosis, the large (p17) and small (p12) subunits, comprising active caspase
      3, are generated via proteolytic processing of a latent proenzyme dimer. Two
      copies of each individual subunit are generated to form an active heterotetramer.
      The tetrameric form of caspase-3 cleaves specific protein substrates within the
      cell, thereby producing the apoptotic phenotype. In contrast to the proenzyme,
      once activated in HeLa cells, caspase-3 is difficult to detect due to its rapid
      degradation. Interestingly, however, enzyme stability and therefore detection of
      active caspase-3 by immunoblot analysis can be restored by treatment of cells
      with a peptide-based caspase-3 selective inhibitor, suggesting that the active
      form can be stabilized through protein-inhibitor interaction. The heteromeric
      active enzyme complex is necessary for its stabilization by inhibitors, as
      expression of the large subunit alone is not stabilized by the presence of
      inhibitors. Our results show for the first time, that synthetic caspase
      inhibitors not only block caspase activity, but may also increase the stability
      of otherwise rapidly degraded mature caspase complexes. Consistent with these
      findings, experiments with a catalytically inactive mutant of caspase-3 show that
      rapid turnover is dependent on the activity of the mature enzyme. Furthermore,
      turnover of otherwise stable active site mutants of capase-3 is rescued by the
      presence of the active enzyme suggesting that turnover can be mediated in trans.

PMID- 14713961
TI  - p53 is a regulator of macrophage differentiation.
AB  - While it is well accepted that p53 plays a role in apoptosis, less is known as to
      its involvement in cell differentiation. Here we show that wild-type p53
      facilitates IL-6-dependent macrophage differentiation. Treatment of M1/2 cells
      expressing the temperature-sensitive p53 143 (Val to Ala) mutant, at the wild
      type conformation, facilitated the appearance of mature macrophages that
      exhibited phagocytic activity. Enhancement of differentiation by the p53 143 (Val
      to Ala) in the wild-type conformation was coupled with the inhibition of
      apoptosis induction by this protein. In agreement with previous studies, we found
      that p53 levels were reduced during p53-dependent macrophage differentiation.
      This occurred when p53 levels before IL-6 stimuli were high. Interestingly, the
      p53 143 (Val to Ala) protein, at the mutant conformation, enhanced macrophage
      differentiation, as did the wild-type conformation, whereas the p53 273 (Arg to
      His) core mutant exerted an inhibitory effect on this pathway. The transcription
      deficient p53 molecules, p53 (22-23) and p53 22,23,143, could not induce p53
      dependent differentiation. Moreover, the p53 (22-23) protein inhibited the p53
      independent differentiation pathway. Interestingly, the p53 (22-23) protein not
      only blocked IL-6-mediated differentiation, but also induced significant
      apoptotic cell death, upon IL-6 stimulation. Taken together, our data show that
      wild-type p53 enhances macrophage differentiation, while various p53 mutant types
      exert different effects on this differentiation pathway.

PMID- 14713962
TI  - [Common water, uncommon qualities].

PMID- 14713963
TI  - [From zero priority to Nobel Prize].

PMID- 14713964
TI  - [Thought-provoking channels].

PMID- 14713965
TI  - [Should high mammographic density be treated?].

PMID- 14713966
TI  - [Pain, functional level and emotional problems of women with osteoporosis and
      vertebral fractures].
AB  - We studied symptoms of pain, anxiety, and depression and physical function in
      postmenopausal women with low bone mass and vertebral fractures. One hundred
      patients attending an out-patient clinic for osteoporosis completed a visual
      analogue scale (VAS) for pain, the Hospital Anxiety Depression Scale (HADS) and
      Short Form (SF-12). Twenty patients also completed the osteoporosis specific form
      QUALEFFO, and were compared to a control group. Maximal pain (VAS) during the
      last week was 5.3 +/- 2.8. Based on HADS, the prevalence of anxiety disorder (29
      %) was significantly higher among the patients than in the norm material; for
      depression, however, there was no difference. For SF-12, the standardized
      physical component summary (PCS) was significantly lower than norm data. No
      difference was found for the mental component summary (MCS). Using QUALEFFO,
      patients reported a worse score for all domains except the mental domain. We
      conclude that Norwegian women with vertebral fractures sustain a high level of
      pain probably leading to an increased level of anxiety, but not to increased
      level of depression compared to age-adjusted norm data.

PMID- 14713967
TI  - [Transcatheter closure of persistent ductus arteriosus].
AB  - BACKGROUND: Transcatheter occlusion of persistent ductus arteriosus has replaced
      surgery as the treatment of choice. We wanted to evaluate the results of this
      treatment in our hospital. MATERIAL AND METHODS: From September 1989 through
      2001, a total of 217 patients with persistent ductus arteriosus were scheduled
      for transcatheter occlusion at Rikshospitalet. Six ducts were too small for
      treatment. In the remaining 211 patients, 224 procedures were performed.
      Patients' median age was 3.4 years (range 4 months-82 years), their median weight
      14 kilograms (range 4-90 kilograms). RESULTS: The Rashkind double umbrella was
      implanted successfully in 61/63 cases, coils in 99/102 cases, and an Amplatzer
      duct occluder in 57/59 cases. Complete closure of the duct was achieved in
      197/211 patients (93%) after reintervention in 11. The complete occlusion rate
      for first procedures were 77% for the Rashkind device, 93% for coils and 100% for
      the Amplatzer plug. Only coils embolised, in 2 out of 102 procedures. Removed
      interventionally, they were replaced by an Amplatzer occluder. One patient
      developed haemolytic anaemia from residual shunting through a coil; the shunt and
      the anaemia both disappeared after implantation of a second coil. INTERPRETATION:
      Transcatheter occlusion of persistent ductus arteriosus is safe and efficient.
      The Amplatzer duct occluder seems superior to the Rashkind double umbrella and
      probably also to coils.

PMID- 14713968
TI  - [Sinus radiography and low-dose CT in the diagnosis of acute sinusitis. ].
AB  - <i>Background. </i>Although CT is considered the method of choice in the
      evaluation of inflammatory sinus disease, plain film radiography is still used,
      as repetitive CT examinations may impart a considerable radiation dose to the
      lens. We designed a new low-dose CT examination and compared this and plain film
      radiography to standard-dose CT. <i>Methods and materials. </i>The new CT low
      dose protocol consisted of ten coronal scans at 40 mAs and 1 mm collimation. 47
      patients referred for acute sinusitis were examined with plain film radiography,
      low-dose and standard-dose CT on the same day. The latter was used as "the gold
      standard". <i>Results. </i>The sensitivity of plain film radiography was low (<
      50 %) except for the maxillary sinus (80 %). The overall sensitivity of low-dose
      CT was 95 % and the specificity 97 %. Effective dose and lens dose of low-dose CT
      were 3 % and 2 % respectively compared to standard-dose CT. Corresponding values
      for conventional radiography were 13 % and 2 %. <i>Interpretation. </i>Low-dose
      CT had image quality comparable to standard-dose CT and a dose to the eye lens
      equal to plain film radiography. Low-dose CT should be the method of choice in
      patients referred for acute sinusitis.

PMID- 14713969
TI  - [Surgical treatment of anal fissure].
AB  - BACKGROUND: Anal fissure is very painful; surgery is warranted when medical
      treatment fails. MATERIAL AND METHOD: We present a retrospective study of 34
      patients (median age 42; 19-63) treated by subcutaneous lateral internal
      sphincterotomy (n = 27) and anal dilatation (n = 7) from 1992 to 2002, carried
      out by a questionnaire on pain, anal incontinence, and treatment result. RESULTS:
      There were no complications or treatment for recurrence of anal fissure. Median
      pain score before surgery was 7.3 on a scale from 0 (no pain) to 10 (worst
      imaginable pain), median 73 months (4-124) after surgery the median score was 0
      (0-5) (p = 0.00). For sphincterotomy (n = 27), the median score was 7.8 before
      surgery and 0 (0-5) after (p = 0.00), for anal dilatation 6 (3-10) before surgery
      and 2 (0-2) (p = 0.01) after. All patients had reduced pain scores after surgery
      but their incontinence scores remained unchanged. Two patients (7%) who had
      previously been dilated or irradiated developed faecal incontinence after
      sphincterotomy. More patients became asymptomatic after sphincterotomy (n = 18;
      67%) than after anal dilatation (n = 4; 57%). INTERPRETATION: Compared to anal
      dilatation, sphincterotomy offers better pain relief for anal fissure. Doing a
      shorter sphincterotomy corresponding to length of the fissure reduces the risk of
      anal incontinence.

PMID- 14713970
TI  - [Ion channels and water channels--a prerequisite for living cells and electric
      signals in the brain].
AB  - Water channels and ion channels are membrane proteins that transport water and
      ions into and out of cells with high selectivity and efficiency. Peter Agre and
      Roderick MacKinnon were awarded the Nobel Prize in chemistry 2003 for their
      discoveries of the structure of water channels and ion channel proteins, thus
      explaining basal mechanisms that are fundamental to all forms of life and in
      particular to the electrical signalling in the brain. These scientific
      achievements answer questions that biophysicists and physiologists have discussed
      since the 19th century.

PMID- 14713971
TI  - [Mammographic density as indicator of breast cancer risk].
AB  - BACKGROUND: Mammograms are useful in identifying early breast cancers before they
      become palpable, but they can also give us information about mammographic
      density, a strong risk factor for breast cancer. Mammographic density has been
      suggested as a biomarker for breast cancer risk and is currently being used as a
      surrogate endpoint for breast cancer in several cancer prevention trials.
      MATERIAL AND METHODS: This article summarises the rationale for using
      mammographic density as a surrogate endpoint for breast cancer, with an emphasis
      on the results that have been published over the last decade. RESULTS:
      Mammographic density not only represents a strong risk factor for breast cancer,
      it is also modifiable. Mammograms are non-invasive and mammographic density is
      readily assessed using computer-assisted methods. INTERPRETATION: The ultimate
      question that remains to be answered is whether a change in mammographic density
      translates to a change in breast cancer risk. This question could easily be
      addressed in the Norwegian Breast Cancer Screening Programme if participants were
      asked the necessary questions when attending the screening programme.

PMID- 14713972
TI  - [Nitrate therapy during and after acute myocardial infarction].
AB  - BACKGROUND: Nitrates have been an integral part of the therapy of ischaemic heart
      disease for more than 130 years. < MATERIAL AND METHODS: We have studied the
      relevant literature on the benefits of therapy with nitrates in acute myocardial
      infarction. RESULTS AND INTERPRETATION: During an acute myocardial infarction,
      intravenous nitroglycerine therapy has demonstrated favourable haemodynamic
      properties, and some studies have shown that nitrates reduce infarct size.
      Whether this could improve prognosis is uncertain. A meta-analysis from 1988
      showed reduced mortality (35 %) of early intravenous nitrate therapy. Newer and
      larger studies have not documented a positive effect. A reason for this
      discrepancy may be the fact that in these studies about half of the
      control/placebo patients, having a low mortality, were treated with
      nitroglycerine. In addition, most of these patients were given thrombolytic and
      antiplatelet therapy. Nitroglycerine administered intravenously is, according to
      present knowledge, recommended during the first 24 hours after an acute
      myocardial infarction. In addition, patients with recurrent ischaemia,
      uncontrolled hypertension and heart failure should also be given nitroglycerine.

PMID- 14713973
TI  - [Glossopharyngeal neuralgia].
AB  - BACKGROUND: Glossopharyngeal neuralgia is a rare but nevertheless important
      condition as it can be very incapacitating and as effective treatment is
      available. MATERIAL AND METHODS: We provide a review of the epidemiology,
      aetiology, differential diagnosis and treatment of this condition based on a
      Medline search. RESULTS AND INTERPRETATION: Glossopharyngeal neuralgia is
      characterised by severe unilateral pain in the posterior pharynx, tonsillar
      fossa, and base of the tongue. It is commonly provoked by swallowing, talking and
      coughing. In most cases the condition is caused by compression of the nerve by an
      artery, usually the postero inferior cerebellar artery. Medical treatment with
      carbamazepin or gabapentin is considered first choice. In patients not responding
      to medical treatment, surgery should be considered; microvascular decompression
      is considered the first choice of surgical treatment.

PMID- 14713974
TI  - [Computed tomography in lung cancer--technique and quality].
AB  - BACKGROUND: There are indications that more patients with lung cancer should be
      offered surgical treatment. The percentage of surgically treated patients varies
      from one region of Norway to the other. The Cancer Registry of Norway has
      received CT examinations from lung cancer patients who were not operated.
      Differences in examination technique and quality were evaluated. MATERIAL AND
      METHODS: Thoracic CT examinations from 42 patients (9 women) from 32 institutions
      were evaluated by three radiologists with regard to technique and quality.
      RESULTS: Twenty-seven examinations (63%) were considered acceptable for
      evaluation of operability, while 15 (37%) were not. The proportion of adequately
      performed examinations was higher with helical CT (22 out of 25 examinations,
      88%) than with conventional, axial scanning (5 out of 17 examinations, 29%).
      There were substantial variations in scanning technique (area, collimation,
      contrast medium, algorithms, and photographic documentation). The majority (n =
      40) of investigations were performed with intravenous contrast medium, two
      without. Contrast medium enhancement and vascular visualisation was judged as
      insufficient in seven examinations. INTERPRETATION: Many examinations were of
      suboptimal quality, inadequate for pre-operative tumour staging. Several
      different examination techniques were documented.

PMID- 14713975
TI  - [Treatment and diagnosis of polymyalgia rheumatica and temporal arteritis].
AB  - BACKGROUND: Studies of polymyalgia rheumatica and temporal arteritis have shown
      that a low initial dose of oral corticosteroids should be preferred. It is,
      however, uncertain whether or not the suggested recommendations have been
      implemented by practising physicians. MATERIAL AND METHODS: Questionnaires were
      mailed to members of the Norwegian association for patients with polymyalgia
      rheumatica or temporal arteritis. RESULTS: The average initial dose of
      prednisolone in polymyalgia rheumatica was 35 mg; 51 of 62 patients were given a
      starting dose exceeding 15 mg. INTERPRETATION: The recommended low initial dose
      of prednisolone has still been not implemented by the majority of general
      practitioners and rheumatologists.

PMID- 14713976
TI  - [Intravenous enzyme substitution therapy in children with Fabry's disease].
AB  - BACKGROUND: Fabry's disease is a X-linked lysosomal storage disorder with
      accumulation of globotriaosylceramide primarily in vascular endothelial cells,
      affecting mainly skin, kidney, heart and brain. Symptoms may appear in 7-8-year
      old children as burning pain in hands and feet; organ damage usually becomes
      evident in adult age. Intravenous enzyme replacement therapy has recently become
      available. PATIENTS: Two brothers, 13.5 and 15 years old, had typical symptoms
      with acroparesthesia, fever, abdominal pain and diarrhoea. There were high levels
      of urinary globotriaosylceramide, low levels of alfagalactosidase A in
      leukocytes, and a single-nucleotide deletion in position 10671 of the
      alfagalactosidase gene (GLA). Both brothers showed slightly abnormal
      echocardiography and one had typical changes on cerebral MRI. Enzyme replacement
      therapy with alfagalactosidase A (Replagal) was started in November 2001. After
      one year of therapy there was clearly clinical improvement with no fever and
      diarrhoea and less pain. The urinary excretion of globotriaosylceramide was
      reduced. No adverse effects were recorded. INTERPRETATION: During 12 months of
      intravenous enzyme replacement therapy in two adolescent subjects with Fabry's
      disease we observed clinical improvement and no adverse effects. We recommend
      greater awareness of Fabry's disease in paediatrics as well as in adult medicine.

PMID- 14713977
TI  - [Pulmonary veno-occlusive disease in a patient with scleroderma and the CREST
      syndrome].
AB  - BACKGROUND: Pulmonary veno-occlusive disease is a rare and poorly understood
      condition that affects the postcapillary pulmonary vasculature, posing diagnostic
      problems and treatment dilemmas. MATERIALS AND METHODS: We present a patient with
      veno-occlusive disease and give a short review on the disease. RESULTS: The
      patient was a 54-year-old female with a history of the CREST variant of
      scleroderma. Admitted with dyspnoea, she was treated with epoprostenol in
      addition to oxygen, diuretics and warfarin. Epoprostenol improved her condition
      initially; her symptoms grew worse during further medical escalation. With an
      attempt to stop epoprostenol, however, she became even more dyspnoeic and
      tolerated best an intermediate dose. She died after three months of treatment
      with signs of progressive right heart failure. INTERPRETATION: Veno-occlusive
      disease may be difficult to diagnose and treat. Clinical signs of pulmonary
      hypertension without evidence of left ventricular failure may give rise to
      suspicion of the disease, and high-resolution CT of the lungs with relatively
      specific findings can be helpful. The prognosis is poor and lung transplantation
      is the only form of effective treatment. Vasodilators as a bridge to
      transplantation must be used with caution because of the risk of intolerance and
      development of pulmonary oedema.

PMID- 14713978
TI  - [Pulmonary arterial hypertension treated with prostacyclin or calcium blockers].
AB  - BACKGROUND: Until recently, medical treatment of pulmonary arterial hypertension
      in Norway has included diuretics, anticoagulation and calcium channel blockers.
      We describe our experience with prostacyclin (epoprostenol) in the treatment of
      this disease. MATERIALS AND METHODS: After diagnostic procedures, 11 patients
      with pulmonary arterial hypertension in functional class III or IV were treated
      with oral calcium channel blockade or intravenous epoprostenol. Choice of medical
      agent was based on right heart catheterisation with acute vasodilator testing.
      Functional capacity and haemodynamics were assessed at referral and after three
      months of therapy. RESULTS: Acute vasodilator testing revealed a much greater
      improvement in haemodynamics in the two patients subsequently treated with
      nifedipine than in the nine patients found to be candidates for epoprostenol. In
      the latter group, a significant median reduction in pulmonary arterial pressure
      of 23% and pulmonary vascular resistance of 59% together with a significant
      increase in cardiac index of 90% and mixed venous oxygen saturation of 17% was
      found after three months of treatment. All 10 survivors significantly improved
      their functional class to I or II and peak exercise oxygen consumption by 60%.
      INTERPRETATION: Epoprostenol is a valuable agent in severe pulmonary arterial
      hypertension for non-responders to acute vasodilator testing. The treatment is
      complex and demands considerable patient involvement.

PMID- 14713979
TI  - [Intraabdominal focal fat infarction].
AB  - BACKGROUND: Intraabdominal focal fat infarction is an acute abdominal condition
      unfamiliar to many doctors. Until recently it has only been diagnosed
      perioperatively, but since 1985 several authors report the use of imaging
      modalities and a spontaneous regression of this disorder. MATERIAL AND METHODS:
      Report of two cases and a review of the literature. RESULTS: Intraabdominal focal
      fat infarction presents characteristic imaging findings with ultrasonography and
      computer tomography. A well-defined lesion of fat with oedema is found in the
      location of maximum tenderness. INTERPRETATION: Doctors dealing with the acute
      abdomen, particularly radiologists and surgeons, should be aware of this
      condition. With a confident diagnosis, unnecessary surgery may be avoided.

PMID- 14713980
TI  - [Vaccination of persons with allergy].

PMID- 14713981
TI  - [Water--for life].
AB  - BACKGROUND: Water is an indispensable nutrient because of its physicochemical
      properties. People seem to consume more water than before although the scientific
      basis for this has not been firmly established. MATERIAL AND METHODS: We present
      a short overview of data retrieved from the databases PubMed and Ovid, with
      particular emphasis on the regulation of water intake and water excretion in
      adults. RESULTS: Water excretion is mainly regulated through the production of
      urine. Anti-diuretic hormone plays a key role. The intake of water is mainly
      governed via the poorly defined sense of thirst. Circumstantial evidence supports
      an increased intake of water to prevent certain cancers and cardiovascular
      diseases. INTERPRETATION: Both excessive hydration and dehydration can cause
      serious illness, in particular in the elderly. There is a lack of firm scientific
      support for the beneficial health effects of increased water intake.

PMID- 14713982
TI  - [Are domestic Cryptosporidium and Giardia infections in Norway underdiagnosed?].
AB  - BACKGROUND: Cryptosporidium and Giardia are recognised as common causes of
      waterborne disease in several countries. In order to describe investigative
      practices for these protozoan parasites in Norway, we surveyed medical
      microbiology laboratories nationwide for faecal screening policies and methods
      used for detection of Cryptosporidium and Giardia. MATERIAL AND METHODS: All
      medical microbiology laboratories in Norway received questionnaires on laboratory
      methods, indications for screening, and numbers of samples investigated over the
      1998-2002 period. RESULTS: Of the 22 laboratories that receive faecal samples, 17
      had established diagnostic routines for Giardia detection, 14 for
      Cryptosporidium. Examination for Giardia cysts was standard procedure in all 17
      laboratories, mainly in specimens from immigrants and travellers returning from
      abroad. Examination for Cryptosporidium was, on the other hand, infrequent. Ten
      of the 14 laboratories reported less than 10 examinations per year. Giardia was
      frequently detected, with 1 to 6% positive samples in the various laboratories.
      Cryptosporidium was seldom detected; all laboratories reported only 0-1 positive
      sample per year. INTERPRETATION: While laboratories frequently screen faecal
      samples for Giardia, screening for Cryptosporidium is rare. Little is known about
      the public health significance of domestic infections with these parasites in
      Norway; further investigation is needed in order to estimate the burden of
      disease they cause and to implement control measures if required.

PMID- 14713983
TI  - [Water-borne disease outbreaks in Norway].
AB  - BACKGROUND: The drinking water in Norway has traditionally been considered being
      of good quality. However, outbreaks related to drinking water are reported every
      year. We review waterborne outbreaks in Norway over the last 15 years, and
      describe the aetiology of and contributory factors in these outbreaks. MATERIALS
      AND METHODS: We compiled data on waterborne outbreaks reported to the Norwegian
      Institute of Public Health and Norwegian Food Control Authority during 1988-2002.
      We included all events in which two or more people fell ill and water was the
      suspected source of infection. RESULTS: Over the 15-year period. 72 outbreaks
      were reported, affecting a total of 10 616 persons. Campylobacter was the cause
      in 26% (19/72) of the outbreaks, norovirus in 18% (13/72). The causative organism
      was unknown in 46% (33/72). The water came from public waterworks in 32 of the 54
      outbreaks for which this information was available (59%); from a private supply
      in the remaining 22. For 62% (16/26) of the outbreaks related to waterworks, the
      water was not disinfected before distribution. None of the private water supplies
      were disinfected. Over the last five years, there were more outbreaks related to
      private supplies. INTERPRETATION: The most important contributory factor to
      waterborne outbreaks in Norway is contamination of the raw water combined with
      missing or faulty disinfecting procedures. To prevent future outbreaks, a
      continuous upgrading of small and private water supplies is needed. Reporting of
      outbreaks is important for the implementation of targeted and effective
      preventive measures.

PMID- 14713985
TI  - [Choice of implants for primary total hip prosthesis].

PMID- 14713986
TI  - [Network to increase resources in the treatment of psychosis].

PMID- 14713989
TI  - [Tuberculosis and civil war].

PMID- 14713991
TI  - [Do selective COX-2-inhibitors increase the risk of myocardial infarction?].

PMID- 14713992
TI  - [Private hospitals and cosmetic surgery].

PMID- 14713993
TI  - [Treatment of psychologically traumatised patients].

PMID- 14713995
TI  - [Urinary tract infections].

PMID- 14713998
TI  - [Influenza or SARS?].

PMID- 14713999
TI  - [Celiac disease is common].

PMID- 14714000
TI  - [Who is responsible when the profit is low?].

PMID- 14714001
TI  - [20 years with AIDS in Norway].

PMID- 14714002
TI  - [CPR and do-not-resuscitate orders].

PMID- 14714003
TI  - [Enterovirus infections diagnosed in middle Norway during the period 1992-2001].
AB  - BACKGROUND: Enteroviruses comprise polioviruses, coxsackieviruses, ECHO viruses
      and the newer enteroviruses. Poliovirus is now declared eradicated from Europe,
      but viruses from the other three groups are still frequent causes of human
      diseases, ranging from mild upper respiratory infections to multi-organ failure.
      MATERIAL AND METHODS: We present a survey of 438 patients with enteroviral
      diseases diagnosed from 1992 to 2001. Enteroviral infections were diagnosed by
      polymerase chain reaction, isolation by tissue culture, and in a few cases by
      electron microscopy. Clinical information was gathered from referral forms and
      patient files. 172 of the isolates were typed. RESULTS: Meningitis,
      gastroenteritis, respiratory disease and fever were the most frequent diseases.
      ECHO virus 30, ECHO virus 6 and coxsackievirus A16 were the most common
      serotypes. 33 % of patients were younger than two years of age. INTERPRETATION:
      Our clinical data demonstrate the wide spectrum of diseases that enterovirus
      infections may cause. We have found a relatively high proportion of patients with
      encephalitis. The association between enterovirus and gastroenteritis is
      discussed. Enteroviruses are the most common cause of aseptic meningitis;
      enterovirus polymerase chain reaction should be performed routinely when dealing
      with this disease. Our data also illustrate the superior sensitivity of
      polymerase chain reaction compared to culture, though culturing is still needed
      as a source of supplementary information.

PMID- 14714004
TI  - [Appendicitis and appendectomy in Norway 1990-2001].
AB  - BACKGROUND: The purpose of this study was to examine the incidence of
      appendicitis and appendectomy in Norway from 1990 to 2001. METHODS: Data were
      compiled from the Norwegian Patient Registry based on ICD-9 and ICD-10 codes for
      appendicitis and appendectomy. Re-admissions after appendectomy were selected
      based on institution and allocation numbers for hospitalisation. RESULTS: Age
      adjusted incidence rates for appendectomy were 117 per 100 000 for men and 116
      per 100 000 for women. Incidence rates were highest among patients aged 10-29.
      Diagnostic accuracy increased from 81% to 86% in men and from 60% to 71% in women
      over the study period. Perforation ratio increased from 12% to 21% in men and
      from 9% to 17% in women. Appendectomy by laparoscopic technique increased during
      1998 to 2001 from 5% to 10% of cases for men and from 9% to 15% of cases for
      women. The proportion of laparoscopic appendectomy was considerably higher in two
      counties (50% and 28% in 2000-2001). Length of hospital stay was shorter after
      laparoscopy (median two days) than after open surgery (median three days), with
      no difference in the rate of re-admission of 4%. INTERPRETATION: Diagnostic
      accuracy and perforation ratio increased over the 1990s. Patients operated upon
      with laparoscopic technique had shorter hospital stays and the same re-admission
      rate compared to patients undergoing conventional surgery. Though the proportion
      of appendectomies done by laparoscopy doubled from 1998 to 2001, the procedure is
      not in commonly use in Norway.

PMID- 14714005
TI  - [Diagnosis and surgical treatment of liquorrhea].
AB  - BACKGROUND: Liquorrhea caused by cerebrospinal fluid fistula may lead to
      meningitis and should be treated surgically. The diagnostic approach and the
      surgery may be difficult and improvements are needed. MATERIAL AND METHODS: We
      present two cases of liquorrhea. A review of the diagnostic and surgical methods
      is given. RESULTS: In both cases the diagnosis was confirmed by detection of beta
      trace protein. In one case the surgery was complicated. This patient had a
      cerebrospinal fluid fistula from the sphenoid sinus. In a third operation,
      performed with sodium fluorescein dying, the fistula was closed. INTERPRETATION:
      Rhinorrhea and meningitis are unspecific signs of a possible cerebrospinal fluid
      fistula. Beta-trace protein is recommended as a diagnostic marker, because this
      protein has the highest positive predictive value for the presence of
      cerebrospinal fluid. High-resolution CT scans are the most helpful imaging
      technique for determining the leakage site, but this is not conclusive in all
      cases. Using sodium fluorescein may give better outcomes of surgical
      interventions.

PMID- 14714006
TI  - [Intracoronary ultrasound in atherosclerotic disease and angioplasty].
AB  - Intracoronary ultrasound is an adjuvant to coronary angiography increasingly used
      in the diagnosis of coronary artery disease and during coronary angioplasty with
      stenting. On the basis of the literature and our own experience, we review the
      value of intracoronary ultrasound. Intracoronary ultrasound is performed as part
      of a cardiac catheterisation with the use of miniature ultrasound transducers in
      the coronary artery. Electronic signals are processed to create images of the
      arterial lumen and wall. In contrast to coronary angiography the ultrasound
      technique can give details of both the arterial wall and the lumen. Detailed
      information of the extent of the atherosclerotic process and its localisation in
      the arterial wall is obtained and the technique allows quantitative measurements.
      Ultrasound guidance improves the quality of coronary angioplasty with balloon
      dilatation alone and especially during stenting. Intracoronary ultrasound has
      significantly increased our knowledge of coronary artery disease; it is
      increasingly being used during coronary interventions.

PMID- 14714007
TI  - [Angiogenesis and hematological malignancies].
AB  - BACKGROUND: It is fairly well documented that the growth and metastasis of solid
      tumours is accompanied by increased formation of new blood vessels emanating from
      a pre-existing vascular bed. Recent findings suggest that angiogenesis also takes
      place in haematological malignancies. These findings suggest that angiogenesis
      might be a potential target for therapy. MATERIALS AND METHODS: A short review is
      presented on the basis of literature identified on PubMed and Medline as well as
      our own data. RESULTS: When surrogate markers are used, such as the plasma
      concentration of angiogenic growth factors or the density of blood vessels within
      the bone marrow, angiogenesis is associated with poor prognosis and treatment
      outcome in haematopoietic malignancy. While human treatment data are scarce,
      findings in animal experiments suggest that anti-angiogenesis might retard
      leukemogenesis. INTERPRETATION: The proliferation and dissemination of malignant
      blood cells seems to be related to increased angiogenesis in the bone marrow.
      Targeting components of the angiogenic process might offer adjunct treatment
      modalities in haematopoietic malignancy.

PMID- 14714008
TI  - [Do-not-resuscitate orders and cardiopulmonary resuscitation at a Norwegian
      department of surgery].
AB  - BACKGROUND: A previous publication indicates a lack of clear guidelines for DNAR
      orders in Norwegian hospitals. The Norwegian Board of Health has recently
      published strict requirements for such a procedure. MATERIAL AND METHODS:
      Patients discharged from a surgical department from 1 March to 31 May 2001 with
      complicated or advanced cancer and/or a postoperative stay of minimum ten days.
      The patient files were studied for information on DNAR orders and/or cardiac
      arrest. RESULTS: 13 out of 69 patients had a DNAR order. In eight of them there
      was either no explanatory note in the files or no correct signature. Three of the
      five other patients had taken part in the discussion, so had next-of-kin in two
      circumstances. Resuscitation was not initiated in any of 14 patients with cardiac
      arrest. Six of these, who had no DNAR order, all had advanced, inoperable cancer
      or serious chronic cardiac and respiratory failure. There were no signs that a
      DNAR order had influenced any other treatment decision. INTERPRETATION: The
      department had a clear procedure for writing DNAR orders but it was followed in
      less than half of the cases.

PMID- 14714010
TI  - [Lung transplantation--established treatment, uncovered need].
AB  - BACKGROUND: Lung transplantation has been a therapeutic option for end-stage
      pulmonary disease in Norway since 1990 and there has been an increasing shortage
      of donor lungs. MATERIAL AND METHODS: The present study evaluates the assessment
      of a total of 409 patients (212 men and 197 women) referred in the period between
      1990 and 2001. RESULTS: The most frequent diagnoses were chronic obstructive
      pulmonary disease (45%), a1-antitrypsin deficiency with emphysema (15%),
      idiopathic pulmonary fibrosis (14%), cystic fibrosis (7%) and sarcoidosis (6%).
      Among patients with chronic obstructive pulmonary disease, 53% were female.
      Numbers of referred and transplanted patients per 100 000 inhabitants did not
      differ significantly between the five health regions of Norway. The number of
      transplantations has been stable, 10-15 per year, while the number of patients on
      the waiting list has gradually increased to 30-40. Mean waiting time has
      increased to 500-600 days. Total mortality rate during assessment and on the
      waiting list was 41%. Patients with idiopathic pulmonary fibrosis and cystic
      fibrosis had significantly higher mortality than patients with chronic
      obstructive pulmonary disease and a1-antitrypsin deficiency with emphysema (63%,
      72%, 26%, 21% respectively). Patients with idiopathic pulmonary fibrosis died
      after a median of 188 days on the waiting list, while patients with cystic
      fibrosis died after a median of 729 days. INTERPRETATION: Patients with
      idiopathic pulmonary fibrosis should be referred earlier and patients with
      idiopathic pulmonary fibrosis and cystic fibrosis should be given higher priority
      on the waiting list.

PMID- 14714009
TI  - [How to scale aerobic capacity in children and adolescents?].
AB  - BACKGROUND: Several studies conclude that VO2peak does not increase in a linear
      way with body mass in children and adolescents. MATERIAL AND METHOD: The paper is
      based on analysis of our own material and relevant literature found by search in
      PubMed. RESULTS AND INTERPRETATION: Despite a dramatic increase in running
      performance during childhood, VO2peak expressed in relation to body mass remains
      remarkably stable in boys and shows a downward tendency in girls from the age of
      13 or 14. However, if VO2peak is related to body surface area (ml kg(-0.67) min(
      1)), the increase in values are more in concert with the increase in running
      performance. Studies of the effect of training on peak oxygen uptake in children
      and adolescents often show little if any improvement when peak oxygen uptake is
      expressed relative to body mass. The reason is the effect of increased body mass
      that masks the increase in peak oxygen uptake. By expressing VO2peak to body
      surface area (ml kg(-0.67) min(-1)), studies have shown similar effect of
      training in children and adolescents as in adults.

PMID- 14714011
TI  - [Extracorporeal surgery and liver autotransplantation].
AB  - BACKGROUND: Though the great majority of hepatic and perihepatic neoplasms may
      very well be treated by conventional surgical techniques, a few patients will
      have lesions seemingly inaccessible by traditional in situ surgical procedures.
      MATERIAL AND METHOD: We present two patients with retrohepatic sarcoma and liver
      haemangioma respectively, treated by hepatectomy, ex situ resection and hepatic
      autotransplantation. RESULTS: The first patient, a 64-year-old man, had a
      completely uneventful postoperative course and had no indication of recurrent
      sarcoma two years later. The second patient, a 29-year-old female with a giant
      hepatic haemangioma developed postoperative hepatic artery thrombosis. Following
      thrombectomy her further course was satisfactory and the patient was discharged
      with normal liver function three weeks postoperatively. INTERPRETATION: Ex situ
      liver surgery (bench surgery) with liver autotransplantation should be considered
      when traditional in situ surgery on the liver or adjacent structures is not
      applicable.

PMID- 14714012
TI  - [Treatment of Helicobacter pylori infection--results and experiences with an
      Internet-based collaboration trial].
AB  - BACKGROUND: Indications for H. pylori treatment as well as treatment regimens
      vary. MATERIAL AND METHODS: This trial compares three regimens with ranitidine
      bismuth citrate (RBC) or omeprazole as first line therapy, evaluates the effect
      of one regimen for retreatment, compares practice at Norwegian centres, and
      evaluates the utility of internet-based collaboration. Consecutive H. pylori
      positive outpatients at 14 centres were randomised to open treatment with one of
      the regimens. Patients in whom the first treatment was unsuccessful were offered
      an "enhanced" regimen with RBC. All participating centres submitted their data to
      a shared database via the internet. RESULTS: The RBC 400 mg, clarithromycin 250
      mg and metronidazole 500 mg regimen, all drugs given twice daily for 7 days, was
      significantly more effective than the other regimens; infections in 141 out of
      146 patients (97%) were successfully eradicated. An enhanced regimen with RBC,
      clarithromycin and metronidazole was less suitable for retreatment after failure.
      There were significant differences in patient age and indication for treatment
      between the centres. The data were of high quality. INTERPRETATION: The regimen
      RBC, clarithromycin and metronidazole was the most effective and seems suitable
      as first-line treatment. The internet collaboration yielded data of high quality
      that disclosed that patients were not uniformly managed. Our collaborative
      approach seems to be a suitable method for quality assurance and the organisation
      of simple clinical multicentre trials.

PMID- 14714013
TI  - [Glycaemic index].
AB  - Glycaemic index is a measure of blood glucose increase two hours after intake of
      food containing 50 g of carbohydrate. The reference is measurements after intake
      of 50 g glucose or white bread containing 50 g carbohydrate, which is set to the
      value of 100. The glycaemic index was developed to help persons with diabetes
      improve their blood glucose control in order to avoid long-term complications.
      Apple can have an index of approximately 40, while a baguette has 95 and
      pumpernickel bread 41. Some observational studies suggest that a carbohydrate
      diet with low glycaemic index may reduce the risk of overweight, diabetes type 2
      and colon cancer. There are at present few published controlled clinical trials
      supporting this conclusion. The food industry and some people working with weight
      reduction have shown interest in using the glycaemic index. The system may easily
      cause confusion and leave the impression that important and nutritious
      carbohydrate-containing foods should be avoided. The glycaemic index could be a
      tool for dieticians and physicians counselling persons with metabolic syndrome,
      overweight, diabetes type 1 or 2.

PMID- 14714014
TI  - [Unpowered scooter injuries].
AB  - BACKGROUND: Injuries caused by the use of unpowered kick scooters in Bergen were
      registered after their introduction on the Norwegian market in 2000. MATERIAL AND
      METHODS: In a prospective one-year registration we found 62 patients with 82
      injuries in Bergen accident and emergency department. RESULTS: Boys and girls
      were injured to the same extent; the age span was from 6 to 53 years, mean age
      11. Most injuries occurred in September. Two thirds injured their arms/hands, one
      sixth their head and one-sixth their legs/feet. Wounds accounted for 37 injuries,
      often in the face (n = 11) or knees (n = 12). Fractures occurred in 34 % (n =
      28); one third needed reduction. Lower arm fractures were most numerous (n = 17),
      the Smith type with volar angulation occurring in almost half of these. Few had
      used safety equipment (n = 5). INTERPRETATION: Kick scooters cause fewer injuries
      than rollerblades and skateboards, but the use of wrist protection and helmet is
      still recommended. Kick scooters should not be used in traffic.

PMID- 14714015
TI  - [Are local steroid injections effective or not?].

PMID- 14714016
TI  - [Coeliac disease--new clinical findings and diagnostic tools].
AB  - Coeliac disease is a disorder characterised by intolerance to wheat gluten and
      related proteins from rye and barley, ingestion of which leads to a harmful
      immune activation in the small intestinal mucosa. The symptoms are often vague
      and do not suggest an intestinal disorder. The diagnosis is often easy once the
      question is raised; it requires a combination of serological tests and small
      intestinal biopsies. Coeliac disease can also exist with a normal serology. The
      trend in many countries is to require less pronounced mucosal abnormalities than
      previously for the diagnosis.

PMID- 14714017
TI  - [Disease mechanisms in coeliac disease].
AB  - Coeliac disease is a chronic inflammatory disorder that is caused by an
      inappropriate immune response in the gut to wheat gluten and similar proteins of
      barley and rye. The disease has a multifactorial aetiology involving multiple
      genes and environmental factors. In recent years we have gained new knowledge of
      the molecular basis of this disorder; this paper gives an overview of the current
      understanding of the pathogenesis of coeliac disease.

PMID- 14714018
TI  - [Dermatitis herpetiformis].
AB  - Dermatitis herpetiformis is characterised by an intensely itchy, chronic,
      papulovesicular eruption, usually on elbows, knees and buttocks. The diagnosis is
      based on granular IgA deposits in the dermal papillae in a perilesional skin
      biopsy analysed by immunofluorescence microscopy. Most patients have subclinical
      celiac disease; a gluten-free diet is effective in most cases. IgA antibodies
      against tissue transglutaminase (TG2) may be involved in the pathogenesis of
      celiac disease with or without dermatitis herpetiformis, and an epidermal
      transglutaminase (TG3) may be the autoantigen in dermatitis herpetiformis. This
      article provides a short review intended for the general practitioner of the
      pathogenesis, diagnosis and treatment of dermatitis herpetiformis.

PMID- 14714019
TI  - [Dietary treatment of coeliac disease and dermatitis herpetiformis].
AB  - Life-long gluten-free diet is the established therapy for coeliac disease and
      dermatitis herpetiformis. Diet therapy allows the intestinal mucosa to recover,
      improves nutrient malabsorption, osteoporosis and a weakened general condition. A
      gluten-free diet is without wheat, rye and barley and related products. Oats
      tested free of contamination by other cereals has recently been allowed for adult
      coeliac patients, but concern still remains regarding its general safety. Gluten
      free flour mixes contain more starch and less proteins, vitamins, minerals and
      fibre compared to regular flour. Recently some questions have been raised as to
      the nutritional quality of the gluten-free diet. Successful therapy with gluten
      free diet requires motivation and dietary counselling, including knowledge of the
      nutritional value of foods, labelling of prepackaged foods and practical training
      in cooking. The local chapters of the Norwegian Coeliac Society are active
      partners, as are the clinical nutritionists that work in most major hospitals.
      The physician making the diagnosis has a duty to see to it that all coeliac
      patients get adequate dietary counselling and management.

PMID- 14714020
TI  - [Waiting list situation at a regional hospital].
AB  - BACKGROUND: In Norway, waiting lists generated by the national VENTSYS system are
      used for hospital management and resource allocation. MATERIALS AND METHODS: Data
      were obtained from monthly reports from VENTSYS and the hospital's annual
      reports. General development in waiting parameters was analysed for the period
      1997-2002. The number of patients waiting in January 2002 was compared to the
      total number of treated patients in 2001 (capacity). RESULTS: Waiting list
      numbers were stable. The number of patients on the lists corresponded to only 8%
      of patients treated. There was no correlation between capacity and number of
      patients on waiting lists for more than twelve months, or between capacity and
      average length of time on a list. Only a few departments had waiting lists
      corresponding to more than a few months' throughput. INTERPRETATION: Long waiting
      lists and waiting time are better explained by poor patient logistics and booking
      systems than by lack of resources.

PMID- 14714021
TI  - [Risk concepts and public health in two different ways--the public health report
      and the WHO annual report].

PMID- 14714022
TI  - [Pharmacies before and after the new legislation].

PMID- 14714026
TI  - [Antiretroviral treatment of HIV infections in poor countries].

PMID- 14714027
TI  - [What will happen with the fight against AIDS?].

PMID- 14714028
TI  - [Passable keeping of medical records].

PMID- 14714029
TI  - [How to measure the effect of risk reduction?].

PMID- 14714030
TI  - [Ethical limitations and limitations of naivety].

PMID- 14714032
TI  - [Incidence and prevention of occupational electrical accidents].

PMID- 14714037
TI  - [Effect and influence].

PMID- 14714038
TI  - [Plastic surgery in a cosmetic market].

PMID- 14714039
TI  - [From lunatic diseases to molecular genetics].

PMID- 14714040
TI  - [A good reason to be on guard].

PMID- 14714041
TI  - [An epidemic of bullous impetigo in the municipality of Austevoll in the year
      2002].
AB  - BACKGROUND: Rising numbers of bullous impetigo caused by Staphylococcus aureus
      resistant to fucidic acid have been seen in Norway over the last few years.
      MATERIAL AND METHODS: We present a population-based cohort study of an epidemic
      in an island community in western Norway with approximately 4450 people. The
      district's doctors agreed upon guidelines for regimes of antibiotic treatment;
      taking specimens for bacteriological examination was made routine procedure. The
      patients included in the study were identified from all patient files from all
      consultations with all doctors in the district. Clinical, therapeutical and
      bacteriological variables were registered. A comparison with the present
      Norwegian guidelines developed by a conference of experts is made. RESULTS: 108
      patients were diagnosed as having bullous impetigo (2.4% of the population).
      Bacteriological swabs were taken from 95 (88%) patients. Staphylococcus aureuswas
      the bacteriologic aetiology in 79 (83%) of these and were found to be resistant
      to fusidic acid in 67 (85%) isolates. DISCUSSION: Our findings support the
      hypothesis that the rising numbers of impetigo might be caused by a clone of
      Staphylococcus aureus that is resistant to fusidic acid.

PMID- 14714042
TI  - [Treatment with etanercept in chronic polyarthritis].
AB  - BACKGROUND: In randomised trials, treatment with anti-tumour necrosis factor
      alpha drugs has been shown to be efficacious for patients with rheumatoid
      arthritis. We analysed the effectiveness and toxicity of etanercept treatment in
      our day-to-day rheumatology practice at the University Hospital of Northern
      Norway. MATERIAL AND METHODS: Patients with active polyarthritis who had failed
      at least three different disease-modifying anti-rheumatic drugs including
      methotrexate and/or combination therapy were consecutively included in an open
      study when they started etanercept therapy (25 mg twice per week subcutaneously).
      During follow up we noted the number of swollen and tender joints, took visual
      analogue scores (0-100 millimetre) for pain and global well-being, administered
      the Modified Health Assessment Questionnaire, performed laboratory tests, and
      took note of side effects. RESULTS: Between April 1999 and July 2001, etanercept
      treatment was initiated in 71 patients. An ACR-20 response (20% improvement
      according to American College of Radiology criteria) occurred in 57% of patients
      after one month of treatment and in 70 % after three months, ACR-50 response in
      24% and 42%, and ACR-70 response in 6% and 20%. While half of all patients
      reported side effects, only five patients (7%) discontinued treatment because of
      them. INTERPRETATION: Etanercept is effective therapy for many patients with
      severe chronic polyarthritis in clinical practice. Short-term side effects occur
      more frequently than reported and seem less frequent with concomitant
      methotrexate therapy. Long-term side effects are still unknown and require close
      monitoring.

PMID- 14714043
TI  - [5-aminosalicylic acid in the treatment of ulcerative colitis and Crohn's
      disease].
AB  - BACKGROUND: Ulcerative colitis and Cohn's disease are characterised by
      exacerbations and remissions. Their aetiology is not known and treatment
      modalities are therefore focused on the inflammation. MATERIAL AND METHODS: A
      review is given of the literature on the clinical efficacy and safety of
      treatment with 5-aminosalicylates. RESULTS: Aminosalicylic acid has a well
      documented efficacy in the acute treatment of mild and moderate ulcerative
      colitis as well as in maintaining remission in these patients. Its value for
      patients with Cohn's disease is at the best modest. There are several possible
      explanations: the variability of disease location, drug disposition and topical
      availability of the active drug. The usefulness of aminosalicylates has been
      demonstrated in the long-term treatment of ulcerative colitis for the prevention
      of colorectal cancer. 5-aminosalicylates have side effects that are comparable
      with placebo. INTERPRETATION: The benefit of 5-aminosalicylic acid is well
      documented in the treatment of active ulcerative colitis and for maintaining
      remission. The opposite is seen in relation to Cohn's disease.

PMID- 14714044
TI  - [A role for antipsychotic agents in the membrane hypothesis of schizophrenia?].
AB  - BACKGROUND: Our picture of the neuronal pathology in schizophrenia remains
      fragmented. Many hypotheses emphasize neurotransmitter receptor dysfunction in
      the development of this condition. Additionally, receptors dominate most research
      on drug therapy in schizophrenia. The so-called membrane hypothesis focuses on
      the role of the neuronal cell membrane in the pathogenesis. MATERIAL AND METHODS:
      On the basis of literature studies, we briefly introduce the membrane hypothesis
      of schizophrenia. We then go on to present results from our own research group,
      which focuses on interactions between antipsychotic agents and cell membranes as
      opposed to drug-receptor interactions. RESULTS AND INTERPRETATION: The membrane
      hypothesis offers an integral model for the neuropathology of schizophrenia.
      However, because of the relatively small number of scientific investigations
      based on the theory, it comes across as weakly documented. Our experiments,
      conducted on model membranes and living cells, point in the direction of direct
      drug-membrane interactions and thus the ability of drugs to influence membrane
      related enzymes without the involvement of a neurotransmitter receptor. These
      results may contribute to an increased understanding of both the neuropathology
      in schizophrenia and the mechanisms of action of antipsychotic agents.

PMID- 14714045
TI  - [Does psychoeducational family intervention improve outcome of schizophrenia?].
AB  - BACKGROUND: Psychoeducational family intervention for schizophrenia was developed
      to reduce stress levels in families in order to improve outcome. MATERIAL AND
      METHODS: Systematic reviews and search in databases (until February 2002,
      "Family" and "Schizophrenia") were used to find randomized controlled studies of
      effect. RESULTS: We found seven studies of short-term family treatment, 15
      studies of long-term treatment comparing it to individual therapy, and seven
      studies comparing family treatment modalities. Long-term family intervention
      reduces the risk of psychotic relapse to about the half within the first two
      years. These methods also shorten hospital stays, improve compliance with
      medication, patients' social functioning and relatives' well-being, and they seem
      to be cost-effective. Single and group family therapies including patients are
      equally efficacious. Relatives' groups do not seem to improve outcome. Several
      factors, such as expressed emotion and duration of illness, modify the effects
      and should be taken into account. INTERPRETATION: In Norway there is a need for
      systematic training of mental health workers in these methods. Family
      intervention should be offered to all persons with schizophrenia who are in
      frequent contact with relatives.

PMID- 14714046
TI  - [Erythrocyte transfusions in a neonatal intensive care unit].
AB  - BACKGROUND: This study present a review of erythrocyte transfusions in a neonatal
      intensive care unit in a Norwegian county hospital. MATERIAL AND METHODS:
      Prospective registration 1991-2002. A leucokyte-depleted erythrocyte solution,
      haematocrit 60%, was used. RESULTS: 28 infants in circulatory collapse received
      30 transfusions because of asphyxia (15), twin-twin transfusion (5), septicaemia
      (3), umbilical cord rupture (3) or other causes (4). Haemoglobin increased 1.8 +/
      1.4 g/dl per 10 ml/kg transfused, compared to 2.6 +/- 1.2 g/dl in 183
      transfusions for anaemia in 122 infants (p < 0.05). All transfusions (n = 115)
      after the first week of life were given because of anaemia, 107 in preterm (< 37
      weeks) infants, and at higher haemoglobin levels in preterm infants with anaemia
      symptoms than in those without (9.7 +/- 1.5 vs. 8.5 +/- .2 g/dl, p < 0.05).
      INTERPRETATION: The rise in haemoglobin was higher for transfusions for anaemia
      than for circulatory collapse, probably because of dilution from other fluids
      given and mobilisation of extravascular fluid in the last group. A substantial
      percentage of the transfusions were given on indications deviating from the
      guidelines.

PMID- 14714047
TI  - [Diagnostic transoesophageal atrial stimulation].
AB  - BACKGROUND: We wanted to evaluate transoesophageal atrial stimulation as a
      diagnostic tool in the evaluation of paroxysmal supraventricular tachycardias.
      MATERIAL AND METHODS: 185 procedures in 177 patients were evaluated
      retrospectively. The main reasons for referral to transoesophageal atrial
      stimulation were documented (52%) or suspected (43%) paroxysmal supraventricular
      tachycardias. The procedure consisted of incremental atrial stimulation to second
      degree A-V block, adding up to three extra stimuli, repeating the protocol with
      isoprenalin 2 and 5 mg/min and completing the procedure with rapid atrial
      stimulation 300-800/min. Induced tachycardias were classified according to the R
      P interval. RESULTS: The procedure was well tolerated. Supraventricular
      tachycardias were induced in 72/96 (75%) of patients with documented paroxysmal
      supraventricular tachycardias and in 41/80 (51%) of patients with suspected
      paroxysmal supraventricular tachycardias. Out of the 101 patients (55%) who were
      referred for invasive electrophysiological study, 79 (78%) had an inducible
      supraventricular tachycardia at transoesophageal stimulation. When stimulation
      resulted in a tachycardia with measurable R-P interval, the accuracy of our
      diagnosis was 87%. INTERPRETATION: Transesophageal atrial stimulation has proved
      to be a useful diagnostic tool in the management of paroxysmal supraventricular
      tachycardias at our hospital. Nearly half the patients required no further
      investigations after transoesophageal atrial stimulation.

PMID- 14714048
TI  - [Cystic fibrosis as seen from the patients' perspective].
AB  - BACKGROUND: We present the results of a study of adults with cystic fibrosis,
      with an emphasis on their experience of symptoms and treatment, future prospects,
      and quality of life. MATERIAL AND METHODS: 86 adults (above the age of 18) with
      cystic fibrosis, recruited through the Norwegian Centre for Cystic Fibrosis. The
      response rate was 84%; average age of respondents 29; 48% were women. RESULTS:
      The most frequently reported symptoms were coughing, phlegm and fatigue. 26%
      experienced great difficulties living with cystic fibrosis. 75% were satisfied
      with their life and 71% had a positive outlook for the future. Lung function was
      the variable most strongly related to symptoms, treatment and outlook for the
      future. INTERPRETATION: It is possible to experience life as good even though one
      is living with a life-threatening disease such as cystic fibrosis.

PMID- 14714049
TI  - [Lactic acidosis as adverse effect of metformin].

PMID- 14714050
TI  - [Hereditary neuropathies].
AB  - BACKGROUND: Hereditary neuropathies constitute a heterogeneous group of diseases
      that make up a significant proportion of peripheral nerve disease cases. MATERIAL
      AND METHODS: The paper is based on a review of recent literature, including
      searches on Medline, and our own clinical and research experience. RESULTS:
      Charcot-Marie-Tooth disease, itself a heterogeneous disease, is the most common
      hereditary neuropathy. Several variants of neuropathy are associated with
      hereditary metabolic disorders. Diagnostic methods include nerve conduction
      velocity studies and electromyography, quantitative sensory testing, molecular
      genetic diagnostic testing, and in selected cases processing of nerve biopsies
      and skin biopsies for determination of epidermal nerve fibre densities.
      INTERPRETATION: A thorough family history of neuropathic symptoms and signs, and
      preferably clinical and electrophysiological examination of relatives is
      essential for the diagnosis of hereditary neuropathy. Molecular genetic analysis
      is promising for accurate classification of these diseases. Nerve biopsy is only
      helpful in selected cases.

PMID- 14714051
TI  - [The genetic basis of muscle disease].
AB  - BACKGROUND: Our understanding of the genetic basis of muscle disease has grown
      dramatically over the last few years. Gene tests are now available for the
      diagnosis of several conditions and molecular research is providing greater
      understanding of pathogenesis. MATERIAL AND METHODS: This article reviews some of
      these advances. RESULTS: Duchenne and Becker muscular dystrophies are allelic
      disorders that differ in age of onset and severity. This can be explained at the
      genetic level by different types of mutations, one giving total protein loss
      (Duchenne) whereas the other results in a less severe deficiency (Becker).
      Facioscapulohumeral muscular dystrophy is associated with deletion involving
      repeated DNA in the sub-telomeric region of chromosome 4. No single gene
      responsible for this disorder has been identified, but we know that deletion size
      correlates with disease severity. Interestingly, complete removal of this region
      does not result in disease. Limb girdle muscular dystrophies share a similar
      phenotype, but genetic and protein studies show that this can be the result of
      mutation in very different types of protein including a protease. There are now
      two forms of myotonic dystrophy, both caused by what are called expansions, an
      increased number of triplet repeats. Both forms demonstrate multisystem
      involvement and in both cases more than one genetic mechanism has been shown to
      be active. Certain muscle diseases appear more common in Scandinavia. Amongst
      these are the distal myopathies in which one type prevalent in Finland has been
      linked to defects in the titin protein. INTERPRETATION: The challenge is now to
      translate the advances in our understanding of genetic mechanism into potential
      forms of treatment. Unfortunately, while much research is focused on techniques
      such as gene therapy, myoblast transplantation and the use of stem cells, these
      have not yet born fruit.

PMID- 14714052
TI  - [Writing information and consent prior to orthopaedic surgery].
AB  - BACKGROUND: In Norway, the Code of Ethics for Doctors and the Patients' Rights
      Act require informed consent before surgery. Written information and consent may
      increase the patient's interest in clinical decision making but will also focus
      on the risks. MATERIAL AND METHODS: This article investigates the attitude of two
      populations of patient to thorough information about the potential risks of
      surgery and their attitude to written information and consent. 91 patients
      accepted for total knee arthroplasty or arthroscopic acromioplasty were offered
      written information material, a consent form, and a questionnaire. RESULTS: All
      patients were in favour of that thorough information should be given about the
      risks of surgery; only three felt that this information caused anxiety. Three
      patients abstained from the operation after having read the information material;
      39 stated that information in writing had improved their ability to decide
      whether or not to accept the operation. 69 patients stated that giving written
      consent is a valuable approach. INTERPRETATION: In patients prepared for total
      knee arthroplasty or arthroscopic acromioplasty, information and consent forms
      with detailed information about risks could be a valuable supplement to oral
      information for the purpose of obtaining truly informed consent.

PMID- 14714053
TI  - [Informed consent prior to surgery].

PMID- 14714054
TI  - [Hospital clinical ethics committee--a useful forum or a foreign bird?].

PMID- 14714058
TI  - [Toward a knowledge-based relief work].

PMID- 14714060
TI  - [About physicians and journalists, risk of death and misunderstandings].

PMID- 14714061
TI  - [Positive drug research].

PMID- 14714062
TI  - [Sick leave as effect target in research].

PMID- 14714063
TI  - [Is current prescription practice of SSRI justifiable?].

PMID- 14714064
TI  - [Thiazides in the treatment of hypertension].

PMID- 14714071
TI  - Prevention of thrombus formation with glyprolines on various models of
      prethrombotic state and thrombosis in rats.
AB  - Peroral administration of peptide Pro-Gly-Pro to 10-11-month-old rats with
      modeled prethrombotic state normalized functions of the anticoagulation system
      and produced a potent antiplatelet effect. Peroral administration of Pro-Gly
      peptide before provocation of thrombin generation and thrombus formation
      prevented death of animals from thrombosis. Experiments on rats with venous
      thrombosis induced by stasis and administration of thrombin showed that
      pretreatment with Pro-Gly peptide decreased the weight of formed thrombi.

PMID- 14714072
TI  - Effect of thyrotropin-releasing hormone on activity of bulbar cardiovascular
      neurons.
AB  - Acute experiments on narcotized cats showed that intravenous injection of
      thyrotropin-releasing hormone (20 microg/kg) inhibited discharge activity of most
      afferent neurons and interneurons in the bulbar cardiovascular center.

PMID- 14714073
TI  - Secretory activity of mast cell during stress: effect of prolyl-glycyl-proline
      and Semax.
AB  - Stress increased secretory activity of mast cells in the mesentery and
      subcutaneous fat of rats. Intraperitoneal injection of Semax and prolyl-glycyl
      proline in doses of 0.05 and 1 mg/kg, respectively, 1 h before stress abolished
      this effect. The test preparations did not modulate secretory activity of mast
      cells in unstressed animals. Semax and prolyl-glycyl-proline in vitro prevented
      activation of mast cells with synacten and acetylcholine. The stabilizing effect
      of peptides on mast cells probably determines their antiulcer activity.

PMID- 14714074
TI  - Demyelination of nerve fibers in the central nervous system caused by chronic
      exposure to natural hydrogen sulfide-containing gas.
AB  - We studied the effect of natural gas from Astrakhan' gas field on rat brain. The
      study revealed a specific effect of natural H(2)S-containing gas on myelin
      sheaths in the brain, which determines its neurotoxicity even at low
      concentrations in the inspired air.

PMID- 14714075
TI  - Slow cooling improved blood lipoprotein composition in hypertensive rats.
AB  - Under normal thermal conditions, hypertensive NISAG rats are characterized by
      lower plasma levels of high-density lipoproteins and increased coefficient of
      atherogenicity compared to normotensive Wistar rats. Slow cooling significantly
      modified fractional composition of plasma lipoproteins in hypertensive rats:
      decreased the content of low-density lipoproteins, markedly increased the content
      of high-density lipoproteins, and normalized coefficient of atherogenicity. Our
      results demonstrated the possibility of correcting disturbances in lipoprotein
      spectrum in essential hypertension by using thermal exposures.

PMID- 14714076
TI  - Effect of the triterpenoid miliacin on the sensitivity of lymphocytes in the
      thymus and spleen to dexamethasone-induced apoptosis.
AB  - We studied the effect of plant triterpenoid miliacin on dexamethasone-induced
      apoptosis in thymocytes and splenocytes. Miliacin produced a protective effect on
      splenocytes by decreasing the degree of DNA fragmentation due to blockade of the
      cascade cell death distally to the intramembrane phosphatidylserine
      translocation.

PMID- 14714077
TI  - Influence of perftoran on structural and metabolic disturbances in the liver
      during experimental atherosclerosis.
AB  - We evaluated whether perftoran can be used for the correction of structural and
      metabolic changes in the liver during alimentary atherosclerosis. Perftoran in a
      dose of 0.3 g/kg normalized the contents of phosphatidylserine, phosphatidic
      acid, and phosphatidylcholine in the plasma membranes of liver cells in rabbits
      feeding an atherogenic diet for 2 months. Architectonics of hepatic trabeculae
      returned to normal, the degree of granular and vacuolar degeneration in
      hepatocytes decreased, and phagocytic activity of macrophages increased.
      Individual peculiarities of the effect of perftoran on structural and metabolic
      changes in the liver were revealed.

PMID- 14714078
TI  - Structure, metabolism, and functions of peripheral blood lymphocytes during long
      term persistence of Epstein-Barr virus.
AB  - Study of surface architectonics, blast transformation potential, and cytochemical
      activity of peripheral blood lymphocytes from children infected with Epstein-Barr
      virus revealed imbalance between structural, metabolic, and functional state of
      lymphocytes. This imbalance persists in delayed period after infection and
      determines long-term viral persistence in the macroorganism.

PMID- 14714079
TI  - Postresuscitation recovery of functional activity of central nervous system in
      rats during combination treatment with mexidol and neuropeptides delta sleep
      inducing peptide and oxytocin.
AB  - In experiments on rats we studied the effects of antioxidant and membrane
      protecting agent mexidol and neuropeptides delta sleep-inducing peptide and
      oxytocin administered during resuscitation after 12-min clinical death.
      Individual and combination treatment with these substances accelerated recovery
      of the neurological status and partially or completely corrected behavioral
      disorders associated with changes in the emotional and motivational status.
      Combined administration of mexidol and oxytocin most significantly promoted
      postresuscitation recovery of functional activity in the central nervous system.

PMID- 14714080
TI  - Dipeptide analog of neurotensin active site prevents the development of
      experimental Parkinson's syndrome in mice.
AB  - Chronic administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (30 mg/kg) to C57BL/6 mice caused death of all animals within 7 days. Dipeptide
      analog of neurotensin active site injected with this neurotoxin protected the
      mice from death even after 2-week intoxication. When younger mice and lower dose
      of neurotoxin (25 mg/kg) were used, all animals survived, but after 2 weeks they
      developed parkinsonian syndrome with muscular rigidity, akinesia, decrease in
      motor and explorative activities. In mice treated with dipeptide analog of
      neurotensin active site these manifestations of oligokinesia caused by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine were less pronounced and the corresponding
      parameters approximated the control values. Possible mechanisms of
      neuroprotective action of neurotensin active site analog are discussed.

PMID- 14714081
TI  - Phagocytic activity and state of bactericidal systems in polymorphonuclear
      leukocytes from patients with Alzheimer's disease.
AB  - Phagocytic activity of peripheral blood neutrophils underwent phase changes in
      patients with Alzheimer's disease. Neutrophils retained the ability to engulf
      microbes, but their digestive activity decreased at the early stage of
      Alzheimer's disease. At the late stage we observed a decrease in the count of
      phagocytizing neutrophils, reduction of myeloperoxidase activity, and increase in
      the content of cationic proteins.

PMID- 14714082
TI  - Stabilizing effect of milk angiogenin on the crystal structure of biological
      fluids.
AB  - We revealed a new property of angiogenin to restore the crystal structure of
      biological fluids (human blood plasma and exudates) impaired in various
      pathologies.

PMID- 14714083
TI  - Oxidative modification of erythrocyte membranes in the acute stage of severe
      craniocerebral trauma and its correction with clonidine.
AB  - Acute posttraumatic stage of severe craniocerebral trauma was characterized by
      considerable activation of lipid peroxidation and exhaustion of the antioxidant
      enzyme system. Oxidative modification of membranes was accompanied by structural
      and functional changes. The antihypoxic effect of clonidine was realized directly
      in the lipid phase of membranes. This preparation inhibited lipid peroxidation
      and activated antioxidant enzymes, which prevented the development of structural
      and functional changes in membranes.

PMID- 14714085
TI  - Production of NO and oxidative destruction of proteins in the placenta during
      normal pregnancy and placental insufficiency.
AB  - Study of NO generation and oxidative destruction of proteins showed
      intensification of these processes in the placenta during normal gestation.
      Activity of NO synthase and the concentration of nitrites in the placenta in
      women with placental insufficiency and spontaneous abortions were below the
      normal. Full-term pregnancy against the background of placental insufficiency was
      associated with a compensatory increase in NO production in the placenta. On the
      other hand, oxidative destruction of proteins increased in placental
      insufficiency irrespective of pregnancy outcome.

PMID- 14714084
TI  - Acception of cholesterol from cells in men of the Russian population correlates
      with concentration of pre-beta1 high-density lipoproteins.
AB  - We analyzed subfraction composition of HDL and cholesterol-acceptor properties of
      the plasma in Russian men with high and low HDL cholesterol. HDL were
      subfractionated by two-dimensional electrophoresis in agarose-polyacrylamide gel.
      The content of pre-beta1 HDL increased in individuals with high concentration of
      HDL cholesterol and strictly correlated with acception of cellular cholesterol in
      both groups.

PMID- 14714086
TI  - Richlocaine in combined therapy of periodontitis.
AB  - The results of combined therapy of chronic moderate generalized periodontitis can
      be improved by adding richlocaine to protocols of drug therapy: the drug reduces
      the time of treatment, prolongs remission, decreases the number of relapses, and
      stabilizes pathological processes in periodontal tissues.

PMID- 14714087
TI  - Effect of richlocaine on proliferative activity of osteoblasts and intracellular
      calcium content in rats.
AB  - We studied the effect of local anesthetic richlocaine on proliferation and
      intracellular calcium content in cultured osteoblasts from rat parietal bone. In
      a concentration of 1 mg/ml this drug produced a cytotoxic effect on osteoblasts.
      In concentrations of 0.01 and 0.001 mg/ml richlocaine in the absence and presence
      of subtoxic dose of sodium cyanide (0.2 mM) increased the number of osteoblasts
      by 15.4 and 36.6 or 13.8 and 38.6%, respectively. In a concentration of 1 mg/ml,
      richlocaine increased the content of cytosolic calcium in osteoblasts by 105%.
      These effects of richlocaine in low concentrations (0.01 and 0.001 mg/ml) can be
      related to stimulation of metabolic processes in osteoblasts.

PMID- 14714088
TI  - Activity of cell immune response and open field behavior in Wistar and OXYS rats.
AB  - The state of the thymus, activity of cell-mediated immunity, and open field
      behavior were compared in Wistar and OXYS rats (premature aging). Early
      involution of the thymus was revealed in OXYS rats, which by the type of
      morphological changes corresponded to accidental involution and was associated
      with low level of delayed hypersensitivity reaction and decreased motor and
      exploratory behavior.

PMID- 14714089
TI  - Structural and functional study of the receptor binding site for FimH adhesin in
      uropathogenic strains of Escherichia coli.
AB  - We evaluated binding capacity of FimH-FocH hybrid adhesins during their
      interaction with model 1M and 3M substrates and epithelial cells. Introduction of
      the Glu89Lys point mutation into the fimH gene induced a new 1M-specific
      phenotype of adhesin. The role of a new pathoadaptive sign in the population of
      E. coli is discussed.

PMID- 14714090
TI  - Predisposition to alcoholism, tryptophan oxygenase activity, and structure of
      intron 6 in the corresponding gene of C57BL/6J, CC57BR/Mv, and BALB/cJ mice.
AB  - Crossbred CC57BR/Mv mice inherited tryptophan oxygenase gene and predisposition
      to alcohol consumption from parent BALB/c and C57BL mice, respectively. In
      CC57BR/Mv mice no relationships were found between alcohol consumption,
      tryptophan oxygenase activity, and single nucleotide substitutions in intron 6 of
      the TDO2 gene associated with predisposition to alcoholism in humans.

PMID- 14714091
TI  - Interaction of GSTM1, GSTT1, and GSTP1 genotypes in determination of
      predisposition to atopic dermatitis.
AB  - The frequency of individual genotypes GSTM1, GSTT1, and GSTP1 and haplotypes was
      determined in patients with atopic dermatitis and healthy children. The actual
      frequency of some haplotypes was far below the theoretical value. Some haplotypes
      were associated with predisposition and resistance to atopic dermatitis.

PMID- 14714092
TI  - Spontaneous activity of the stomach and large intestine in healthy individuals
      and patients with tumors before and after gastrectomy and colectomy.
AB  - We studied the distribution of main frequencies of spontaneous activity (in the
      range of 2-4 cycles/min) of the stomach and large intestine in healthy
      individuals and patients with stomach and colon cancer before and after
      gastrectomy and resection or total colectomy. The rhythm was recorded
      noninvasively (from body surface) with Ag/AgCl electrodes connected to a 3
      channel portable electrogastrograph. We determined general peculiarities of
      rhythm formation in the stomach and large intestine in healthy individuals on an
      empty stomach and after mixed feeding and evaluated changes in spontaneous
      activity in patients with stomach and colon cancer before and after gastrectomy,
      resection, or total colectomy. Rhythmic activity of the stomach was coordinated
      with that of the large intestine in healthy individuals, but not in patients with
      tumors before the start of specific therapy. Multichannel cutaneous
      electrogastroenterography and recording of spontaneous electrical activity in the
      epigastric and perianal regions reflect functional relationships between the
      stomach and large intestine.

PMID- 14714093
TI  - Proliferative activity and level of steroid hormone receptors in the myometrium
      and myoma nodes in different phases of menstrual cycle.
AB  - We compared proliferative activity and levels of steroid receptors in the
      myometrium and myoma nodes in patients with uterine myoma in different phases of
      menstrual cycle. Maximum proliferative activity was observed at the periphery of
      myoma nodes in the the secretory phase of the cycle. The content of progesterone
      receptors at the periphery and in the center of myoma nodes was lower in the
      proliferative phase of the cycle than in the secretory phase. Steroid regulation
      of proliferative activity in the myoma nodes in the the secretory phase through
      modulation of the content of progesterone receptors is hypothesized.

PMID- 14714094
TI  - Modification of delayed radiation-induced reactions of duodenal vessels and mast
      cells in old rats.
AB  - Pronounced ultrastructural changes in vessels and mast cells were observed in
      duodenal lamina propria of Wistar rats 1 year after single whole-body gamma
      irradiation in a dose of 7.5 Gy. Inhibition of adrenocortical function with
      methopyrone reduced structural damage and improved animal survival.

PMID- 14714095
TI  - Relationship between behavioral selection and primary and secondary immune
      response in wild gray rats.
AB  - The main characteristics of primary and secondary immune response (number of
      antibody producing cells and the amount of produced antibodies) are reduced in
      rats selected by elimination of aggressive behavior in comparison with animals
      selected by stimulation of this behavior. In parallel, the reaction of the
      pituitary-adrenal system during immune response was modified in these rats.
      Presumably, the differences in immune reactions of rats selected by contrast
      behavior are determined by changes in reactivity of the pituitary-adrenal system
      to stress and immune stimulation during selection.

PMID- 14714096
TI  - Criteria for predicting the outcome of pheochromocytoma by the
      immunohistochemical and electron microscopic findings.
AB  - Morphological examination of 22 functionally active adrenal pheochromocytomas was
      carried out. The content of catecholamine granules in tumor cells and in the
      number of sustentacular cells tended to decrease in metastasizing tumors.
      Electron microscopy showed two types of sustentacular cells and the possibility
      of their apoptotic death.

PMID- 14714097
TI  - Dynamics of structural changes in the retina during long-term exposure to bright
      light.
AB  - Exposure to high-intensity light led to pronounced destructive changes in the
      retina and focal loss of layers formed by neurosensory cells in rats. Photoinjury
      led to progressive decrease in the numerical density of nuclei in the outer
      nuclear layer (by 30% after 2 days, by 75% after 1 week, and more than by 90%
      after 2 weeks of exposure). After 30 days the photosensory layer completely
      disappeared, while the outer nuclear layer was presented by solitary nuclei of
      neurosensory cells.

PMID- 14714098
TI  - OXYS rats as a model of senile cataract.
AB  - Changes in the lens appear by the age of 2 months in early aging OXYS rats, at
      the age of 6 months these changes are detected in 100% animals, and by 12 months
      both eyes are involved. According to biomicroscopy findings, predominant forms of
      cataract are vesicular, annular, and dendritic, located in the cortical layer
      and/or nucleus of the lens. Light and electron microscopy showed morphological
      changes involving all structural components of the lens: epithelial degeneration
      progressing with age, deformation of fiber architectonics, and appearance of
      uneven condensations. Cataract in OXYS rats corresponds to senile cataract, which
      makes this rat strain a unique model for studies of the pathogenesis of
      involutive cataract and elaboration of methods for its prevention and correction.

PMID- 14714099
TI  - Use of polytetrafluorethylene films for closing of abdominal cavity under
      conditions of experimental peritonitis.
AB  - Four variants of polytetrafluorethylene films differing by size of micropores and
      manufacturing technology were used for closing of the abdominal cavity under
      conditions of experimental peritonitis in rats. The results of tensiometry and
      planimetry helped us to select the optimal variant of polytetrafluorethylene film
      characterized by sufficient strength, minimum size of micropores, and causing
      minimum complications.

PMID- 14714100
TI  - Methodological approaches to deciphering the etiological structure of non
      nosocomial pneumonia.
AB  - Comparative analysis of the efficiency of PCR and microbiological methods for
      deciphering of the etiological structure of non-nosocomial pneumonias
      demonstrated the diagnostic significance of detecting Streptococcus pneumoniae
      DNA in the blood, but not sputum. Mechanisms of penetration of S. pneumoniae into
      the blood are discussed.

PMID- 14714101
TI  - Study of the relationship between pulse duration and the accuracy of evaluation
      of the critical frequency of light flashing.
AB  - The relationship between pulse duration and accuracy of evaluation of the
      critical frequency of light flashing was studied. The accuracy of measurement of
      this parameter increased if the duration of light pulses decreased. Our results
      indicate that the optimal duration of light pulses for determining critical
      frequency of light flashes is 3-5 msec.

PMID- 14714102
TI  - Effects of MDMA (ecstasy), and multiple drugs use on (simulated) driving
      performance and traffic safety.
AB  - RATIONALE: The effects of MDMA on driving behaviour are not clear, since the
      direct effects of MDMA on cognitive performance are reported as not generally
      negative. OBJECTIVES: To assess in an advanced driving simulator acute effects on
      simulated driving behaviour and heart rate of MDMA, and effects of polydrug use.
      METHODS: A group of young participants who had indicated that they regularly used
      MDMA were asked to complete test rides in an advanced driving simulator, shortly
      after the use of MDMA, just before going to a party. They were tested again after
      having visited the "rave", while they were under the influence of MDMA and a
      number of different other active drugs. Participants were also tested sober, at a
      comparable time at night. Separately, a control group of participants was
      included in the experiment. RESULTS: Driving performance in the sense of lateral
      and longitudinal vehicle control was not greatly affected after MDMA, but
      deteriorated after multiple drug use. The most striking result was the apparent
      decreased sense for risk taking, both after MDMA and after multiple drug use.
      This was clear from gap acceptance data, while the ultimate indicator of unsafe
      driving, accident involvement or even causation, was increased by 100% and 150%,
      respectively. CONCLUSIONS: Driving under the influence of MDMA alone is certainly
      not safe; however, driving back (home) after a dance party ("rave") where MDMA
      users regularly combine MDMA with a host of other drugs can be described as
      extremely dangerous.

PMID- 14714103
TI  - Genomics of the ccoNOQP-encoded cbb3 oxidase complex in bacteria.
AB  - Many bacteria adapt to microoxic conditions by synthesizing a particular
      cytochrome c oxidase (cbb3) complex with a high affinity for O2, encoded by the
      ccoNOQP operon. A survey of genome databases indicates that ccoNOQP sequences are
      widespread in all sub-branches of Proteobacteria but otherwise are found only in
      bacteria of the CFB group ( Cytophaga, Flexibacter, Bacteroides). Our analysis of
      available genome sequences suggests four major strategies of regulating ccoNOQP
      expression in response to O2. The most widespread strategy involves direct
      regulation by the O2-responsive protein Fnr. The second strategy involves an O2
      insensitive paralogue of Fnr, FixK, whose expression is regulated by the O2
      responding FixLJ two-component system. A third strategy of mixed regulation
      operates in bacteria carrying both fnr and fixLJ-fixKgenes. Another, not yet
      identified, strategy is likely to operate in the epsilon-Proteobacteria
      Helicobacter pylori and Campylobacter jejuni which lack fnr and fixLJ-fixK genes.
      The FixLJ strategy appears specific for the alpha-subclass of Proteobacteria but
      is not restricted to rhizobia in which it was originally discovered.

PMID- 14714104
TI  - Specificity grouping of the accessory gene regulator quorum-sensing system of
      Staphylococcus epidermidis is linked to infection.
AB  - Staphylococcus epidermidis represents the most frequent pathogen involved in
      nosocomial infections and infections of indwelling medical devices. The strain-to
      strain variation of the gene encoding the quorum-sensing pheromone of S.
      epidermidis as well as the correlation between specificity groups and origin from
      infection were determined. The pro-pheromone gene was highly conserved and showed
      infrequent, non-synonymous, single-nucleotide polymorphisms that led to
      conservative amino acid exchanges only. Importantly, one specificity group was
      significantly more frequent among strains isolated from infection. The finding
      that quorum-sensing specificity groups are linked to infection demonstrates the
      relevance of quorum-sensing for virulence in this critical human pathogen and
      contributes to the scientific basis needed for the development of quorum-sensing
      targeting drugs.

PMID- 14714105
TI  - Validation of the new Intensive Care Nursing Scoring System (ICNSS).
AB  - OBJECTIVES: To validate a new Intensive Care Nursing Scoring System (ICNSS).
      DESIGN: Retrospective data collection. SETTING: Adult 19-bed intensive care unit
      (ICU) in a tertiary care university hospital. PATIENTS: A total of 1,538 patient
      records of which 30 documents were included in the validation. MEASUREMENTS AND
      RESULTS: Data included admission scores of the Acute Physiology and Chronic
      Health Evaluation II (APACHE II) and the Simplified Acute Physiology Scores II
      (SAPS II), daily Therapeutic Intervention Scores (TISS) and ICNSS scores. Data
      were compared using Spearman's correlation, t-test and chi-square test. Receiver
      operating characteristics (ROC) curve analysis was used to assess the ability of
      ICNSS and TISS to predict mortality. Intra-class correlation, percentage
      agreement and kappa statistics were used to test the validity of given scores.
      Nursing workload assessment using ICNSS showed that medical and emergency
      operated patients caused a greater nursing workload than electively operated
      patients (p<0.001). Six variables of the sub-scale that described vital function
      nursing accounted for 27.4% of the variation of SAPS II and for 37% of the
      variation of APACHE II. The ICNSS sub-scale of vital function nursing accounted
      for a ROC area of 0.91. In the validity of the given ICNSS scores, kappa was 0.81
      and weighted kappa 0.82. CONCLUSIONS: Nursing workload varied between the
      different admission types. ICNSS explained a similar percentage of the variation
      of the admission scores of APACHE II and SAPSS II as TISS and discriminated
      between non-survivors and survivors. ICNSS is a suitable nursing workload
      instrument to be used with the TISS score.

PMID- 14714106
TI  - The effect of waiving consent on enrollment in a sepsis trial.
AB  - OBJECTIVE: Illustration of the difficulties in approaching critically ill
      patients for informed consent for inclusion into a randomized controlled trial
      and the impact of a waiver of consent from the patient's next of kin in the
      conduction of such studies. DESIGN: Descriptive survey of the inclusion rates
      into the Ger-Inf-05 study before and after a waiver of consent from the patient's
      next of kin. SETTING: Nineteen intensive care units in France. PATIENTS: Septic
      shock patients (n=300) included in a placebo-controlled randomized double-blind
      study on the efficacy and safety of a 7-day treatment with 50 mg hydrocortisone
      every 6 h intravenously and 50 microg fludrocortisone every 24 h orally.
      INTERVENTION: Introduction, 10 months after the beginning of the study, of a
      waiver of consent from the patient's next of kin if it was not present at the
      time of the patient's inclusion. MEASUREMENTS AND RESULTS: The mean inclusion
      rate was four patients per month before the introduction of the waiver of consent
      and increased to 10 patients per month after the study amendment including the
      waiver of consent. Informed consent was obtained from the patient himself or
      herself in 10 patients (3%) and from next of kin in 70 patients (23%). For the
      220 other patients (74%), the investigators could not contact the responsible
      relative within the inclusion period. CONCLUSIONS: Recruitment rate in the Ger
      Inf-05 study was clearly improved after the waiver of consent from the patient's
      next of kin. This probably contributed to the successful completion of the study.

PMID- 14714107
TI  - Clinical cure and survival in Gram-positive ventilator-associated pneumonia:
      retrospective analysis of two double-blind studies comparing linezolid with
      vancomycin.
AB  - OBJECTIVE: To assess the effect of baseline variables, including treatment, on
      clinical cure and survival rates in patients with Gram-positive, ventilator
      associated pneumonia (VAP). DESIGN: Retrospective analysis of two randomized,
      double-blind studies. SETTING: Multinational study with 134 sites. PATIENTS: 544
      patients with suspected Gram-positive VAP, including 264 with documented Gram
      positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP.
      INTERVENTIONS: Linezolid 600 mg or vancomycin 1 g every 12 h for 7-21 days, each
      with aztreonam. MEASUREMENTS AND RESULTS: Clinical cure rates assessed 12-28 days
      after the end of therapy and excluding indeterminate or missing outcomes
      significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic
      regression showed that linezolid was an independent predictor of clinical cure
      with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for
      MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset.
      Logistic regression showed that linezolid was an independent predictor of
      survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and
      4.6 for MRSA VAP. CONCLUSIONS: Initial linezolid therapy was associated with
      significantly better clinical cure and survival rates than was initial vancomycin
      therapy in patients with MRSA VAP.

PMID- 14714109
TI  - Failure to confer cardioprotection and to increase the expression of heat-shock
      protein 70 by preconditioning with a kappa-opioid receptor agonist during
      ischaemia and reperfusion in streptozotocin-induced diabetic rats.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the effects of
      preconditioning on injury and expression of heat shock proteins 70 in diabetic
      rat hearts. METHODS: Diabetes was induced by an intraperitoneal injection of 65
      mg kg(-1) streptozotocin. Daily subcutaneous injection of 4 IU insulin started 2
      weeks after streptozotocin treatment for 4 weeks. Rats were preconditioned by
      intravenous injection of 10 mg kg(-1) U50,488H, a selective kappa-opioid receptor
      agonist (U50,488H preconditioning). The effects of U50,488H preconditioning had
      previously been shown to be blocked by a selective kappa-opioid receptor
      antagonist, nor-binaltorphimine. Twenty-four hours later, rats were subjected to
      30 min of regional ischaemia by occlusion of the left coronary artery followed by
      4 h of reperfusion. Infarct size was determined at the end of reperfusion. Stress
      inducible and constitutive heat shock proteins 70 were analysed at the end of
      ischaemia and reperfusion by Western blotting. RESULTS: Myocardial infarcts
      induced by ischaemia and reperfusion were greater in diabetic rats. U50,488H
      preconditioning significantly reduced the infarct size and increased the
      expression of stress-inducible heat-shock protein 70 in normal rats. The effects
      of U50,488H preconditioning were abolished in streptozotocin-induced diabetic
      rats, but restored by insulin replacement. CONCLUSION/INTERPRETATION: In addition
      to a greater susceptibility to ischaemic insults, the delayed cardioprotection of
      U50,488H preconditioning was lost, which could at least partly be due to impaired
      synthesis of stress-inducible heat-shock protein 70 in diabetic rats.

PMID- 14714108
TI  - Lung volume in mechanically ventilated patients: measurement by simplified helium
      dilution compared to quantitative CT scan.
AB  - OBJECTIVE: We describe a simplified helium dilution technique to measure end
      expiratory lung volume (EELV) in mechanically ventilated patients. We assessed
      both its accuracy in comparison with quantitative computerized tomography (CT)
      and its precision. DESIGN AND SETTING: Prospective human study. PATIENTS: Twenty
      one mechanically ventilated ALI/ARDS patients. INTERVENTIONS: All patients
      underwent a spiral CT scan of the thorax during an end-expiratory occlusion. From
      the CT scan we computed the gas volume of the lungs (EELVCT). Within a few
      minutes, a rebreathing bag, containing a known amount of helium, was connected to
      the endotracheal tube, and the gas mixture diluted in the patient's lungs by
      delivering at least ten large tidal volumes. From the final helium concentration,
      EELV could be calculated by a standard formula (EELVHe). MEASUREMENT AND RESULTS:
      The results obtained by the two techniques showed a good correlation
      (EELVHe=208+0.858xEELV(CT), r=0.941; P<0.001). Bias between the two techniques
      was 32.5+/-202.8 ml (95% limits of agreement were -373 ml and +438 ml), with a
      mean absolute difference of 15%. The amount of pathological tissue did not affect
      the difference between the two techniques, while the amount of hyperinflated
      tissue did. Bias between two repeated helium EELV measurements was -24+/-83 ml
      (95% limits of agreement were -191 ml and +141 ml), with a mean absolute
      difference of 6.3%. CONCLUSIONS: The proposed helium dilution technique is simple
      and reproducible. The negligible bias and the acceptable level of agreement
      support its use as a practical alternative to CT for measuring EELV in
      mechanically ventilated ARDS patients.

PMID- 14714110
TI  - Clinical and electrophysiological characterization of a novel mutation R863X in
      HERG C-terminus associated with long QT syndrome.
AB  - We have found a novel nonsense mutation in the C-terminus of HERG in a four
      generation Chinese family with long QT syndrome and investigated the molecular
      mechanism of this mutation in vitro. Six family members, including the proband,
      were clinically affected. Syncope and ventricular tachycardia of torsades de
      pointes were triggered by startling or emotional stress, and beta-adrenergic
      blockade treatment was ineffective. Haplotype analysis showed that only LQT2
      markers cosegregated with the disease, and sequence analysis revealed a
      substitution of T with C at nucleotide position 2770 of the HERG gene (U04270),
      which creates a stop codon at amino acid position 863 (R863X) of the HERG
      protein, leading to a deletion of 296 amino acids. Whole cell patch clamp studies
      showed that the R863X HERG could not induce time-dependent current. Coexpression
      of R863X with wild-type HERG showed reduced current densities and accelerated
      voltage-dependent inactivation of HERG channels. Subcellular localization of
      R863X-EGFP revealed that the mutant did not traffic to the cell surface. These
      data suggest that R863X failed to form functional HERG channels, contributing to
      a prolongation of the QT interval and long QT syndrome with a dominant phenotype.
      These findings provide new insights into the structure-function relationships of
      the HERG C-terminus.

PMID- 14714111
TI  - Differential gene expression pattern in alveolar macrophages of patients with
      sarcoidosis and tuberculosis.
AB  - Sarcoidosis is a multisystem granulomatous disorder of unknown origin
      characterized by the presence of epithelioid granulomata in the affected organs.
      Histological and clinical similarities between sarcoidosis and tuberculosis
      caused by M. tuberculosis suggest a shared underlying pathophysiology. However,
      specific markers are needed. This study examined the differential gene expression
      pattern in alveolar macrophages of patients with granulomatous disorders. The
      differential mRNA regulation pattern of alveolar macrophages in the
      bronchoalveolar lavage of healthy controls was compared to that of patients with
      sarcoidosis and tuberculosis by means of differential display reverse
      transcription PCR. Comparative analysis of 2,498 PCR products in controls,
      sarcoidosis, and tuberculosis revealed a differential regulation of expressed
      sequence tags in only 6.5%. 1.8% showed a shared expression pattern between
      sarcoidosis and tuberculosis in contrast to the control. It can be assumed that
      these alterations are associated with common granulomatous features. In contrast,
      3.0% of the amplified sequence tags showed specific up- or downregulation in
      sarcoidosis and 1.6% in tuberculosis. These data indicate a significant
      proportion of common granuloma-associated features, independent of the origin of
      the granulomatous disorder.

PMID- 14714113
TI  - Would a vitamin help, doctor?

PMID- 14714115
TI  - Alcoholism-related phenotypes and genetic variants of the CB1 receptor.
AB  - OBJECTIVE: Neurotransmitter release of GABAergic and glutamatergic neurons may be
      significantly influenced by cannabinoid CB1 receptors located at presynaptic
      nerve terminals. GABA and glutamate have been reported to be involved in the
      pathogenesis of severe alcohol withdrawal-induced seizures and delirium tremens.
      The aim of this study is to test the potential influence of a bi-allelic
      cannabinoid receptor gene (CNR1) polymorphism (G1359A) on severe alcohol
      withdrawal syndromes. METHODS: Based upon a sample size estimation, 196 subjects
      meeting DSM IV and ICD10 criteria for alcohol dependence and 210 non-alcoholic
      controls were recruited for study. CB1 polymorphisms were determined using
      polymerase chain reaction (PCR). History of alcohol withdrawal-induced delirium
      tremens, seizures and other alcohol withdrawal-related phenotypes were obtained
      using the SSAGA (Semi-Structured Assessment of Genetics in Alcoholism). Data were
      corroborated with information from the inpatients' clinical files. RESULTS:
      Allele frequencies of the CNR1 G1359A polymorphism were within the range reported
      by previous studies. After correcting for multiple testing, no association of the
      A- or G-allele of CNR1 polymorphism with a history of alcohol withdrawal-induced
      seizures was detected. In addition, no significant relationships with other
      alcoholism-related phenotypes were found. CONCLUSION: This study failed to
      confirm an earlier report of a potential role of a CNR1 polymorphism in the
      pathogenesis of delirium tremens.

PMID- 14714116
TI  - A pilot study on a gene-hormone interaction in female suicide attempts.
AB  - This one-year naturalistic study included all suicide attempters in a catchment
      area. In the first published set of analyses, an association between menses and
      suicide attempts was replicated. According to the polymorphism of the serotonin
      transporter promoter area, the subjects can be classified as S individuals (s/s
      or s/l) or L individuals (l/l). In the second published set of analyses, L
      females appeared protected from suicide attempts since they were underrepresented
      among female (and not male) attempters. This new, unpublished third set of
      analyses tested for an interaction between the same polymorphism and low hormonal
      activity (during menses and menopause). In fertile female attempters, the
      proportion of L women in the menses (41%, 7/17) was significantly higher than
      expected in the population (15.5 %) and almost significantly higher than in S
      female attempters (22%,19/87). L females were also overrepresented in
      postmenopausal attempters. Despite sample size limitations, this gene-hormone
      interaction needs to be further investigated in female suicide attempters.

PMID- 14714117
TI  - Social anxiety spectrum.
AB  - The aim of this paper is to provide the prevalence rates of mild, moderate and
      severe symptoms of social anxiety in a sample of high school students and to
      analyze gender differences and associated impairment levels within these three
      levels of severity. Five hundred and twenty students were assessed with the
      Social Anxiety Spectrum Self-Report (SHY-SR), a questionnaire that explores
      social anxiety spectrum. By applying two cut-off scores determined on a separate
      sample by using ROC analysis, the large majority (73.3 %) of subjects were
      classified as low scorers, 9% as medium scorers and 17.7% as high scorers. Fears
      related to social situations were reported both by high and medium scorers.
      Functional impairment defined by avoidance and school difficulties was more
      common among high scorers, but it was also reported to a significant extent by
      medium scorers. Compared to low and medium scorers, high scorers showed a higher
      F/M ratio (about 4:1) and a more homogeneous symptomatological profile in the two
      genders. In conclusion, our report confirms, in line with the literature, that
      even moderate levels of social anxiety are associated with significant functional
      impairment and distress for the individuals.

PMID- 14714118
TI  - Affective priming in schizophrenia with and without affective negative symptoms.
AB  - In the present study automatic perceptual sensitivity to facial affect
      information was examined in chronic schizophrenic patients. An affective priming
      task including subliminal and supraliminal presentations of sad and happy facial
      affect was administered to schizophrenia patients with a flat affect expression
      (n = 30), schizophrenia patients suffering from anhedonia (n = 30), schizophrenia
      patients not suffering from anhedonia or flat affect (n = 28), and a group of
      healthy controls (n = 30). Subjects had to judge valence of neutral Chinese
      ideographs. Anhedonic and flat affect patients but not patients without affect
      symptoms were found to be sensitive to negative facial affect on an automatic
      processing level. None of the schizophrenic patient groups but healthy controls
      showed a subliminal valence-congruent priming effect based on positive facial
      affect. Anhedonia as assessed by standardised psychiatric rating was related to a
      subliminal sensitivity to negative facial expression and a valence-inverted
      perception of positive facial expression. This pattern of results is largely
      consistent with predictions derived from Meehl's model of anhedonia. The aversive
      automatic perception of positive facial expression primarily found in anhedonic
      patients but also in schizophrenic control patients could lie in structural
      disturbances concerning the regulation of intimacy and distance.

PMID- 14714119
TI  - Inter- and intraoperator reliability of brain tissue measures using magnetic
      resonance imaging.
AB  - Grey matter, white matter and cerebrospinal volume in the human brain were
      measured using magnetic resonance image analysis software BRAINS. Ten volunteers
      were scanned in the MR sequence (3D-SPGR; 1.5-mm slice thickness and T2 images;
      3mm slice thickness). Two operators obtained ten volume measures of grey
      matter,white matter and cerebrospinal fluid (CSF) in the intracranial box,
      frontal box, temporal box, parietal box and occipital box. The same data set of
      ten scans was segmented and the volumes measured on a second occasion by one
      operator using the same procedure. The interoperator and intraoperator
      reliabilities for measures of the three brain tissues were very good, with
      reliability coefficients (intraclass correlation coefficients) ranging between
      0.971 and 0.999. The segmentation and measurement are useful for volumetric
      studies in the human brain using BRAINS.

PMID- 14714120
TI  - Fluoxetine once every third day in the treatment of major depressive disorder.
AB  - OBJECTIVE: Fluoxetine and its active metabolite norfluoxetine have long half
      lives. We postulate that, owing to the long elimination half-life and the time to
      reach steady-state level in plasma is nearly four weeks, patients diagnosed with
      major depressive disorder might be treated with fluoxetine taken once every third
      day, after being treated initially during 4 weeks with daily doses of fluoxetine.
      METHODS: In this open label, 12-weeks, randomized, prospective study, patients
      diagnosed with DSM-IV major depressive disorder were randomly assigned into 1 of
      3 treatment groups. Thirty-four patients took 20 mg and 32 patients took 40 mg of
      fluoxetine daily throughout the study. Twenty-nine patients had been taking 20 mg
      of fluoxetine daily for 4 weeks of the study initially, and then were switched to
      20 mg fluoxetine once every third day regime. The severity of depression was
      assessed by Hamilton Depression Rating Scale (HDRS) and Clinical Global
      Impressions- Severity Scale (CGI-S). Response was defined as a 50% or greater
      reduction of the baseline HDRS total score. After defining a strict criterion of
      relapse, time to relapse was estimated using survival analyses (Kaplan-Meier
      method). RESULTS: The repeated measures analysis of variance (ANOVA) of HDRS
      found a significant time effect (F = 464.04, df = 1.00, p < 0.001), but no
      significant group effects (F = 0.84, df = 2.00,p = 0.433) from baseline through
      week 12. The proportion of responders was not significantly different between the
      treatment groups at the endpoint. Survival analyses showed, however, a
      significant delayed mean time to relapse in patients treated with 40 mg of
      fluoxetine daily compared to either patients treated with 20 mg of fluoxetine
      daily or 20 mg fluoxetine once every third day. The mean times to relapse were
      79.8, 70.8, and 70.5 days, respectively. Fluoxetine was associated with some
      adverse events in 46.3% of patients. The most frequently occurring adverse event
      was insomnia. CONCLUSION: It is proposed that either every third day or daily
      dosing with the same dose of fluoxetine could treat the patients with major
      depressive disorder during the acute and continuation period of treatment.
      Nevertheless, higher daily dose of fluoxetine has a reduced relapse rate compared
      to that of the lower daily dose.

PMID- 14714121
TI  - Associations between anxiety disorders and physical illness.
AB  - OBJECTIVE: In contrast to the literature on the association of depression with
      medical illness, less is known about the comorbidity among anxiety and somatic
      disorders. Although associations between anxiety disorders and medical illnesses
      have been reported, prior studies have not adjusted for the effects of gender,
      substance abuse/dependence, and depression. This study examined the patterns of
      comorbidity of anxiety disorders and physical illnesses. METHOD: A total of 262
      probands were selected from treatment settings or were randomly recruited from
      the community. DSM-III-R diagnoses were obtained based on direct interview (SADS)
      or family history information, and lifetime history of numerous medical illnesses
      were obtained. RESULTS: Patients with a lifetime anxiety disorder reported higher
      rates of several medical illnesses than did persons without anxiety. After
      controlling for the effects of gender, comorbid substance abuse/dependence and/or
      depression, significant associations were found between anxiety disorder and
      cardiac disorders (OR = 4.6), hypertension (OR = 2.4), gastrointestinal problems
      (OR = 2.4), genitourinary disorders (OR = 3.5), and migraine (OR = 5.0). A
      similar pattern was observed for probands with panic or generalized anxiety
      disorder (GAD). CONCLUSIONS: Anxiety disorders were associated with a specific
      pattern of cardiac disorders, hypertension, gastrointestinal problems,
      genitourinary difficulties, and migraine; individuals presenting with anxiety
      disorders or medical illness need therefore to be evaluated carefully for
      comorbidity.

PMID- 14714122
TI  - German research network on schizophrenia-bridging the gap between research and
      care.
AB  - The German Research Network on Schizophrenia (GRNS) is a nationwide network of
      presently 16 psychiatric university departments, 14 state and district hospitals,
      as well as six local networks of psychiatric practices and general practitioners,
      which are collaborating in about 25 interrelated, multicentre projects on
      schizophrenia research. The GRNS aims to intensify collaboration and knowledge
      exchange between leading research institutions and qualified routine care
      facilities, both within (horizontal network) and between (vertical network) the
      two levels of research and care, in order to create the scientific preconditions
      for optimization of care in patients with schizophrenia. With respect to illness
      development, the network is organized into two main "Project Networks" (PN).
      Whereas PN I targets the implementation of early detection and early intervention
      strategies, PN II aims at optimization of acute and long-term treatment,
      especially in first-episode patients. PN II also includes projects aiming at
      improvement of rehabilitation, particularly in patients with residual symptoms.
      Furthermore, there is a "Special Network" on molecular and pharmaco-genetics.
      Several more general projects address fighting stigma and discrimination, health
      care economy, continuing medical education, quality assurance, and methodology.
      The network is mainly funded by the German Ministry for Research spanning a
      period of 5 years.

PMID- 14714128
TI  - Health status and voice outcome after treatment for T1a glottic carcinoma.
AB  - Radiotherapy as well as endoscopic laser surgery as the most widely used
      treatment modalities for T1a glottic carcinoma cause minor morbidity and
      negligible mortality and result in more or less comparable, excellent cure and
      larynx preservation rates. Therefore, other outcome measures such as voice
      related problems and health status are important factors in the choice of
      treatment for T1a glottic cancer. The present study focuses on voice-related
      problems in the daily life of patients treated by radiotherapy or endoscopic
      laser surgery for T1a glottic cancer. Self ratings on health status assessed by
      means of COOP/WONCA health status charts and voice problems evaluated with a
      validated voice-specific questionnaire (the Voice Handicap Index) and overall
      judgment on voice quality were obtained. A total of 102 patients (56 treated by
      endoscopic laser surgery and 46 treated by radiotherapy) with at least 1-year
      follow-up were included. Response scores were high: 52 (93%) patients after
      endoscopic laser surgery versus 40 (87%) patients after radiation therapy
      completed and returned the questionnaires. A high percentage of patients reported
      voice problems in daily life: 58% of the patients following radiotherapy and 40%
      of the patients following endoscopic treatment had abnormal VHI scores. The
      difference between both treatment modalities proved to be significant. No
      significant differences were found concerning health status or overall judgment
      of voice quality. Moderate correlations were found between total VHI score and
      voice quality judgment and the COOP/WONCA social activities chart. This study
      reveals that treatment for T1a glottic cancer often does result in voice problems
      in daily life, negatively influencing patients social activities. Patients
      selected for endoscopic laser surgery on average report fewer voice-related
      problems than those who underwent radiotherapy.

PMID- 14714129
TI  - Extent of surgical intervention in case of N0 neck in head and neck cancer
      patients.

PMID- 14714130
TI  - Cyclin D1 expression does not effect cell proliferation in adenoid cystic
      carcinoma of the salivary gland.
AB  - Adenoid cystic carcinoma is a malignant tumor of salivary gland origin. It tends
      to grow slowly, but shows frequent recurrence and metastasis. Cyclin D1, a cell
      cycle regulation protein, has been reported to be overexpressed in various types
      of cancer and to correlate with poor survival of the patients. However, the
      prognostic significance of cyclin D1 expression in ACC of the salivary glands has
      not yet been determined. To evaluate the role of cyclin D1 in the biological
      regulation of ACC, we constitutively expressed an antisense cyclin D1
      complementary DNA (cDNA) in an established ACC cell line that exhibits high
      endogenous expression of cyclin D1. The effect of cyclin D1 expression on in
      vitro cell growth and cell cycle were examined. In addition, we also examined the
      immunohistochemical expression of cyclin D1 protein in 31 cases of ACC of the
      salivary gland and correlated its expression with proliferative activity or
      prognosis. There were no significant differences of the in vitro growth and in
      the percentage of the total cell population in the G1 phase and S phase between
      antisense cyclin D1 clones and control clones. Thirty-two percent of tumors
      derived from surgical specimens examined were immunohistochemically positive for
      cyclin D1 protein. No association was found between cyclin D1 expression and cell
      proliferation or the clinical outcome of the patients. It is concluded that
      cyclin D1 overexpression alone does not induce a marked increase in the
      proliferative activity of ACC cells and that expression of this protein is not
      linked to poor prognosis in adenoid cystic carcinoma of the salivary gland.

PMID- 14714131
TI  - Sinonasal haemangiopericytoma: a case report.
AB  - Haemangiopericytoma (HPC) is a rare vascular tumour that is thought to originate
      from the vascular pericytes of Zimmerman. HPC may arise in any part of the body,
      and from 15 to 30% of these tumours are found in the head and neck, with a rare
      involvement of the sinonasal region The main symptoms of nasal HPC, epistaxis and
      nasal obstruction, are not typical. The final diagnosis is based on the
      histopathology and immunochemistry, and whether the tumour is benign or malignant
      is defined on the basis of the clinical history. HPC located in the sinonasal
      area is generally benign. We report the case of a young woman with a sinonasal
      mass histologically proven to be haemangiopericytoma. The patient underwent
      surgical treatment by means of mid-facial degloving after embolisation of the
      maxillary artery. After a careful 3-year follow-up, the patient is disease free
      and healthy.

PMID- 14714132
TI  - Medical treatment of pulmonary hydatidosis: complications and surgical
      management.
AB  - Pulmonary hydatidosis is more frequently encountered in children than in adults.
      Chemotherapy with oral administration of particular antihelminthic agents
      (mebendazole and albendazole) has proved to be effective. This treatment,
      however, may be associated with serious complications that require surgical
      management. The aim of this study was to define the limitations of medical
      treatment, the subsequent complications, and their management. During a 16-year
      period (1985-2001), 36 children with pulmonary hydatidosis (Echinococcus
      cysticus) were medically treated. Oral antihelminthic agents (mebendazole until
      1992 and albendazole thereafter) were given to all these patients. During this
      treatment, 11 patients developed complications requiring surgical intervention.
      In seven children, pleural empyema, or the presence of inflammatory residual
      fluid, was noted. The remaining four developed pulmonary abscess combined with
      fluid collection within the pleural cavity. In all complicated cases, the mean
      size of the cysts exceeded 6 cm in diameter at the beginning of medical
      treatment. At operation, suturing of communicating bronchi was insecure due to
      inflammation. Postoperatively, three patients had air leakage from the bronchial
      tree, requiring continuous suction and prolonged hospitalization. One patient
      presented with pneumothorax 4 months postoperatively and was operated on again.
      Overall, long-term results were good. We concluded that a) large pulmonary
      hydatid cysts should not be treated medically, b) incomplete expectoration of the
      cyst contents after the parasite death may lead to infection through bronchial
      communication, and c) patients surgically treated for complications following
      medical treatment are hospitalized twice as long as patients surgically treated
      in the first place.

PMID- 14714133
TI  - Upregulated expression of EGF and TGF-alpha in the proximal respiratory
      epithelium in the human hypoplastic lung in congenital diaphragmatic hernia.
AB  - Newborn infants with congenital diaphragmatic hernia (CDH) still have a high
      mortality rate. Epidermal growth factor (EGF) and transforming growth factor
      alpha (TGF-alpha) are peptide growth factors involved in the fetal lung growth
      and development. The EGF and TGF-alpha have been reported to promote pulmonary
      branching activity and alveolar type-II pneumocyte proliferation. Epidermal
      growth factor and TGF-alpha immunoreactivity and mRNA expression in the bronchial
      and bronchiolar epithelium is maximal during early fetal life and barely
      detectable in the proximal airways of neonatal lung. The purpose of this study
      was to determine protein and gene expression of EGF and TGF-alpha in CDH lung in
      order to elucidate the potential role of these growth factors in the pathogenesis
      of pulmonary hypoplasia in CDH. Lung tissue specimens were obtained from archival
      lung tissue from 11 patients with CDH and 5 controls. Indirect
      immunohistochemistry was performed using ABC method with anti-EGF and anti-TGF
      alpha antibodies. In situ hybridization was performed using EGF and TGF-alpha
      specific digoxigenin-labeled oligonucleotide probes. The most striking difference
      between hypoplastic CDH lung and control lung was the strong EGF and TGF-alpha
      mRNA expression and immunoreactivity in the bronchial and bronchiolar epithelium
      in CDH lung. The upregulated protein and gene expression of EGF and TGF-alpha in
      the proximal airways in the CDH hypoplastic lung suggests persistence of fetal
      stage of pulmonary airway development in CDH.

PMID- 14714134
TI  - The herbal medicine Rikkunshi-to stimulates and coordinates the gastric
      myoelectric activity in post-operative dyspeptic children after gastrointestinal
      surgery.
AB  - Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, has been used for the
      symptomatic relief of adult patients with dyspepsia. However, its mechanism has
      yet to be fully elucidated. The aim of this study is to evaluate the effect of TJ
      43 on the gastric myoelectric activity in post-operative dyspeptic patients,
      whose symptoms persisted for over 1 year after gastrointestinal surgery.
      Electrogastrography (EGG) recordings were performed to calculate the
      biomechanical parameters on the dominant peak frequency (DPF). Eight pediatric
      patients with dyspeptic symptoms after gastrointestinal surgery were examined and
      six age-matched children without any dyspeptic symptoms were used as controls,
      and they were compared with nine age-matched children without any dyspeptic
      symptoms after gastrointestinal surgery as subcontrols. All patients exhibited
      symptomatic relief after the administration of TJ-43, and the mean symptom score
      decreased significantly after the treatment of TJ-43 over a 1-month period (
      P<0.0001). The variability index (VI) and the percentage of normal waves (PNW)
      were calculated as irregularity parameters of DPF. The power ratio (PR) was
      calculated as a parameter of the gastric contractile activity. There were no
      significant differences in the VI and PNW between the controls and patients
      during the postprandial state after therapy, even though significant differences
      existed regarding those parameters between the controls and patients before the
      therapy. There were no significant differences in the DPF, VI, and PNW between
      the controls and subcontrols. Furthermore, PR exhibited a significant increase
      after therapy ( P<0.05). However, there was a significant difference in the PR
      between the controls and subcontrols ( P<0.05). Postprandial dip was observed in
      all control subjects, eight patients in the subcontrols, and two patients after
      administration of TJ-43, respectively. An abnormal gastric electrical activity
      therefore seems to be an important factor in the pathophysiology of post
      operative dyspeptic children. The coordinating and stimulating effect of TJ-43 on
      the gastric myoelectric activity therefore seems to play an important role in the
      reduction of dyspeptic symptoms.

PMID- 14714135
TI  - Radiotherapy-induced secondary cranial neoplasms in children.
AB  - BACKGROUND: Secondary malignant neoplasms (SMN) in CNS tumor survivors has become
      problem of increasing concern over the last 20 years. These tumors usually occur
      in a different site from the primary brain tumor several years after treatment.
      CASE REPORT: We report secondary cranial malignant neoplasms in three patients
      who were treated with irradiation and chemotherapy for their primary brain
      tumors. The first case is a male survivor of an orbital rhabdomyosarcoma who
      developed a meningioma 8 years later. The other two cases are female survivors of
      ependymomas who were irradiated at the age of 3 and developed secondary gliomas 8
      and 17 years after therapy respectively. CONCLUSION: Patients carry a risk of
      developing SMNs many years later since irradiation is still an important part of
      the treatment. An SMN may have a benign course, as in meningioma, or be a dilemma
      for the patient, as in glioblastoma.

PMID- 14714136
TI  - Angular and spectral sensitivity of fly photoreceptors. III. Dependence on the
      pupil mechanism in the blowfly Calliphora.
AB  - A wave optics model for the facet lens-rhabdomere system of fly eyes is used to
      analyze the dependence of the angular and spectral sensitivity of R1-6
      photoreceptors on the pupil mechanism. This assembly of light-absorbing pigment
      granules in the soma interacts with the waveguide modes propagating in the
      rhabdomere. A fly rhabdomere carries two modes in the middle wavelength range and
      four modes at short wavelengths, depending on the rhabdomere diameter and the
      angle of the incident light flux. The extension of the mode to outside the
      rhabdomere strongly depends on wavelength, and this dependence plays a
      determinant role in the light control function of the pupil. The absorbance
      spectrum of the pigment in the pupil granules is severely depressed at short
      wavelengths by waveguide effects, resulting in a distinct blue peak. Accordingly,
      pupil closure suppresses the photoreceptor's spectral sensitivity much more in
      the blue-green than in the UV. The pupil only narrows the angular sensitivity at
      short wavelengths. The geometrical size of the rhabdomere governs the angular
      sensitivity of fly photoreceptors in the dark-adapted state, but diffraction
      takes over in the fully light-adapted state.

PMID- 14714137
TI  - Different patterns of circadian oscillation in the suprachiasmatic nucleus of
      hamster, mouse, and rat.
AB  - Although spontaneous neural firing in the mammalian suprachiasmatic nucleus is
      accepted to peak once during mid-subjective day, dual activity peaks have been
      reported in horizontal brain slices taken from hamsters. These two peaks were
      interpreted as new evidence for the theory of dual circadian oscillators and
      raised the expectation that such activity would be found in other circadian model
      systems. We examined hamster, mouse, and rat slices in both coronal and
      horizontal planes and found a second peak of activity only in hamster horizontal
      preparations. This raises interesting questions about the relative circadian
      physiology of these important experimental animals.

PMID- 14714138
TI  - Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal
      rat.
AB  - Renal vasoconstriction with resultant tissue hypoxia, especially in the renal
      medulla, has been suggested to play a role in contrast media (CM)-induced
      nephropathy. In this study we investigated the effects of injection of the non
      ionic low-osmolar CM iopromide with and without pretreatment with the selective
      adenosine A1-receptor antagonist DPCPX. The effects were evaluated on regional
      renal blood flow, outer medullary oxygen tension (PO2) and urine output in normal
      anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic
      changes while oxygen microelectrodes were used for oxygen measurements. The A1
      receptor antagonist per se elevated glomerular filtration rate (+44%), cortical
      blood flow (+15%) and urine output (threefold) while reducing outer medullary PO2
      (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and
      PO2 (-80%) but did not affect cortical blood flow. Urine output increased 28-fold
      by CM while arterial blood pressure was reduced. The CM-mediated effect on
      haemodynamics, PO2, urine output and blood pressure was unaffected by the A1
      receptor antagonist. Adenosine A1-receptors are not important mediators of the
      depression of outer medullary blood flow and PO2 caused by the CM iopromide in
      the normal rat; however, A1-receptors are tonically active to regulate renal
      haemodynamics, PO2 and urine production during normal physiological conditions.

PMID- 14714139
TI  - Phase-inversion tissue harmonic imaging compared with conventional B-mode
      ultrasound in the evaluation of pancreatic lesions.
AB  - The aim of this study was to compare the diagnostic sensitivity, specificity, and
      image quality of conventional B-mode US (BM) and phase-inversion tissue harmonic
      imaging (PTHI) regarding pancreatic pathology. In a prospective study, 107
      patients, aged between 28 and 85 years, underwent US examinations of the pancreas
      with both BM and PTHI in a randomly chosen order. As diagnostic reference, either
      contrast-enhanced CT or MRI examinations of the upper abdomen were obtained in
      all patients. Sensitivity and specificity were evaluated using the Student's t
      test. Differences in overall image quality, lesion conspicuity, fluid-solid
      differentiation, and delineation of the pancreatic tail were analyzed using
      Wilcoxon's signed ranks test and Bowker's symmetry test. Sixteen of 107 examined
      patients (15%) were non-diagnostic and excluded due to technical limitations such
      as abdominal gas. A total of 60 pancreatic lesions (cysts, acute pancreatitis,
      dilatation of the pancreatic duct, calcifications, and solid tumors) were
      diagnosed by CT or MRI. Phase-inversion tissue harmonic imaging had a higher
      sensitivity of 70% (14 of 20) than BM (60%; 24 of 40) for the detection of
      pancreatic lesions; however, the difference was not statistically significant (
      p=0.46). In the assessment of lesions <1 cm of size, PTHI had a sensitivity of
      70% and BM 46.7%, whereby the difference again was not statistically significant.
      Phase-inversion tissue harmonic imaging proved to be superior to BM regarding
      overall image quality ( p<0.0001), lesion conspicuity ( p=0.0045), and fluid
      solid differentiation ( p=0.0002), as well as the delineation of the pancreatic
      tail ( p<0.0001). These differences were statistically significant. The
      statistically significant improvement of image quality with regards to lesion
      conspicuity, fluid-solid differentiation, and delineation of the pancreatic tail
      favors the use of PTHI when evaluating the pancreas with US. Sensitivity for
      pancreatic lesions is increased with PTHI in comparison with conventional
      sonography (BM), especially in lesions <1 cm in diameter, although the difference
      was not statistically significant.

PMID- 14714140
TI  - Interventional radiology in the management of complications after liver
      transplantation.
AB  - The arrival of new surgical transplantation techniques, such as split living
      donor or auxiliary liver transplantation, have increased the incidence of
      vascular and biliary complications. The causes, symptoms, and diagnostic
      modalities of arterial, portal caval, and biliary complications are detailed.
      Interventional techniques, such as balloon angioplasty and stent placement in the
      arterial and portal tree, as well as biliary interventional techniques, are
      discussed.

PMID- 14714141
TI  - Detection of the putative cis-region involved in the induction by a Pyricularia
      oryzae elicitor of the promoter of a gene encoding phenylalanine ammonia-lyase in
      rice.
AB  - A rice PAL (phenylalanine ammonia-lyase) gene sequence ( rPAL-P5), which is
      highly similar to and likely the same as a previously described rice ZB8PAL gene,
      including the 5'-upstream and exon I coding regions of PAL, was isolated using
      PCR amplification. The expression of several PALs, including rPAL-P5, was
      strongly induced following inoculation with Pyricularia oryzae or treatment with
      a P. oryzae elicitor. To identify the promoter region induced by the P. oryzae
      elicitor, we constructed and subsequently transformed rPAL-P5 promoter deletion
      series into rice calli using particle bombardment. Results from both elicitor
      inducible reporter gene and gel mobility shift assays demonstrated that the
      sequence -349 to -256 of the rPAL-P5 promoter includes a cis-element involved in
      the induction of P. oryzae.

PMID- 14714142
TI  - Antifungal activity of stilbenes in in vitro bioassays and in transgenic Populus
      expressing a gene encoding pinosylvin synthase.
AB  - The effect of two stilbene compounds, pinosylvin and resveratrol, on the growth
      of several fungi was evaluated in plate tests. Wood decay tests were carried out
      with birch and aspen samples impregnated with the two stilbenes. In plate
      experiments, resveratrol had an enhancing effect on growth at concentrations
      where pinosylvin was already enough to prevent the growth of most fungi studied.
      Pinosylvin impregnated at 0.2% (w/w) concentration significantly reduced the
      decay caused by all fungi except Phellinus tremulae. In contrast, a resveratrol
      content of 0.8%, did not protect the wood from decay. A pinosylvin-synthase
      encoding gene from Pinus sylvestris was transferred into aspen ( Populus tremula)
      and two hybrid aspen clones ( Populus tremulax tremuloides) by Agrobacterium
      tumefaciens-mediated transformation. Transgenic plants accumulated pinosylvin
      synthase-specific mRNA and showed stilbene synthase enzyme activity in vitro.
      Transgenic aspen line H4 showed increased resistance to Phellinus tremulae, while
      two hybrid aspen transformants decayed faster than the control trees. However, we
      were unable to detect the accumulation of stilbenes in the transgenic plantlets.

PMID- 14714143
TI  - Surgical Implant Generation Network (SIGN) intramedullary nailing of open
      fractures of the tibia.
AB  - We treated 36 open tibial fractures (32 patients) by primary intramedullary
      nailing and debridement and treatment of open wounds. There were 13 grade I, 14
      grade II and 9 grade III according to Gustilo-Anderson classification. After a
      minimum follow-up of 8 months, there were two cases of superficial infection and
      one of deep infection. Thirty-one fractures united within 6 months with a mean
      period to union of 22 weeks. There were four delayed unions and one non-union.
      There was a longer union time and a higher rate of delayed or non-union in the
      complex and/or comminuted grade IIIB fractures. Intramedullary nailing, with
      appropriate soft-tissue treatment, gives good results in the treatment of open
      tibial fractures.

PMID- 14714145
TI  - Ultrasound of the elbow.
AB  - The elbow is an important synovial hinge joint of the upper extremity. This joint
      represents a common site of musculoskeletal symptomatology, affecting all age
      groups. The advantages of ultrasound imaging of the elbow include easy
      availability, multiplanar capability and the ability to assess structures
      dynamically. Patient symptomatology and site of maximal tenderness can be
      directly correlated with imaging findings. Comparison is easily made with the
      contralateral side. Particular strengths include the ability to assess para
      articular structures, such as regional tendons and ligaments, in addition to
      assessment of joint effusions, loose bodies and regional bursae. With operator
      experience and excellent technique, ultrasound is a valuable imaging tool for
      assessment of disorders of the elbow joint.

PMID- 14714147
TI  - Postpartum osteoporosis associated with proximal tibial stress fracture.
AB  - A 33-year-old woman presented with acute nonspecific knee pain, 6 months
      postpartum. MR imaging, computed tomography and radiography were performed and a
      proximal tibia plateau insufficiency fracture was detected. Bone densitometry
      demonstrated mild postpartum osteoporosis. To our knowledge these findings have
      not been described in this location and in this clinical setting. The etiology of
      the atraumatic fracture of the tibia is presumed to be due to a low bone mineral
      density. The bone loss was probably due to pregnancy, lactation and postpartum
      hormonal changes. There were no other inciting causes and the patient was
      normocalcemic. We discuss the presence of a postpartum stress fracture in a
      hitherto undescribed site in a patient who had lactated following an
      uncomplicated pregnancy and had no other identifiable cause for a stress
      fracture.

PMID- 14714148
TI  - Periosteal osteoblastoma of the distal femur.
AB  - Osteoblastomas located on the surface of the cortical bone, so-called periosteal
      osteoblastomas, are extremely rare. We report on a case of periosteal
      osteoblastoma arising from the posterior surface of the right distal femur in a
      17-year-old man. Roentgenographic, computed tomographic, magnetic resonance
      imaging, and histologic features of the case are presented. Periosteal
      osteoblastoma should be radiologically and histologically differentiated from
      myositis ossificans, avulsive cortical irregularity syndrome, osteoid osteoma,
      parosteal osteosarcoma, periosteal osteosarcoma, and high-grade surface
      osteosarcoma. Although periosteal osteoblastoma is rare, this tumor should be
      included in the differential diagnosis of surface-type bone tumors.

PMID- 14714149
TI  - Idiopathic osteoarthritis: time to change paradigms?
AB  - Standard theory assumes that osteoarthritis is a catabolic disease, characterised
      by cartilage destruction brought about by absolute or relative overload. This
      theory fits the observed facts in secondary osteoarthritis, but when it is tested
      against the idiopathic disease, the disease profile includes many phenomena which
      are difficult to reconcile with the overload theory. It incorporates, for
      example, no adequate explanation for the prevalence patterns observed in human
      and primate epidemiology, the idiosyncratic distribution, the sparing of the
      ankle and wrist joints, the production of osteoarthritis by immobilisation, the
      anabolic dominance of early disease, and several pathological changes including
      the osteophyte, the reduplicated tide-mark, and the extra-articular contracture.
      The evidence better fits the concept of two different diseases with a possible,
      but not obligatory, final common pathway. In the case of the idiopathic disease,
      the unused arc hypothesis proposed 50 years ago by Harrison et al., reinforced
      with the concepts of synovial stasis and positive feedback, tests better against
      the evidence than the overload paradigm. These proposed adjuncts to the
      hypothesis are speculative and as yet untested. The results could be of more than
      academic interest. If the unused arc hypothesis turns out to be correct,
      idiopathic osteoarthritis should be preventable and conceivably, in its early
      stages, arrestable.

PMID- 14714150
TI  - Micro total analysis system (micro-TAS) in biotechnology.
AB  - Nanobiotechnology raises fascinating possibilities for new analytical assays in
      various fields such as bioelectronic assembly, biomechanics and sampling
      techniques, as well as in chips or micromachined devices. Recently,
      nanotechnology has greatly impacted biotechnological research with its potential
      applications in smart devices that can operate at the level of molecular
      manipulation. Micro total analysis system (micro-TAS) offers the potential for
      highly efficient, simultaneous analysis of a large number of biologically
      important molecules in genomic, proteomic and metabolic studies. This review aims
      to describe the present state-of-the-art of microsystems for use in
      biotechnological research, medicine and diagnostics.

PMID- 14714151
TI  - Bacillus amyloliquefaciens phage endolysin can enhance permeability of
      Pseudomonas aeruginosa outer membrane and induce cell lysis.
AB  - To determine the function of the C-terminal region of Bacillus amyloliquefaciens
      phage endolysin on Pseudomonas aeruginosa lysis, the permeabilization of the
      outer membrane of P. aeruginosa was analyzed. Glu-15 to His (E15H) and Thr-32 to
      Glu (T32E) substitutions were introduced into the Bacillus phage endolysin.
      Neither E15H nor T32E substitution induced enzymatic and antibacterial
      activities. These two, Glu-15 and Thr-32, were considered to be the active center
      of the enzyme. The addition of purified E15H and T32E proteins to P. aeruginosa
      cells induced the release of periplasmic beta-lactamase from the cells,
      indicating that both proteins enhance permeabilization of the outer membrane.
      However, the addition of E15H and T32E proteins to P. aeruginosa cells did not
      induce the release of cytoplasmic ATP from the cells. These results indicate that
      the antibacterial activity of the endolysin requires both the C-terminal
      enhancement of the permeabilization of the P. aeruginosa outer membrane and N
      terminal enzymatic activity.

PMID- 14714152
TI  - Identification of New World monkey MHC-DRB alleles using PCR, DGGE and direct
      sequencing.
AB  - Identification of New World monkey MHC-DRB alleles has previously relied upon
      labor-intensive cloning and sequencing techniques. Here we describe a rapid and
      unambiguous way to distinguish DRB alleles in New World monkeys using the
      polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE),
      and direct sequencing. The highly variable second exon of New World monkey DRB
      alleles was amplified using generic DRB primers and alleles were separated by
      DGGE. DNA was then reamplified from plugs removed from the gel and alleles were
      determined using fluorescent-based sequencing. The validity of this typing
      procedure was confirmed by the identification of all DRB alleles previously
      characterized by cloning and sequencing techniques from an individual cotton-top
      tamarin. Importantly, our analysis revealed DRB alleles not previously identified
      in this reference animal. Following validation of our technique, the protocol was
      employed for the characterization of MHC-DRB alleles in four other species of New
      World monkey: the pygmy marmoset, white-faced saki monkey, long-haired spider
      monkey and owl monkey. Using this technique, we identified five alleles from the
      cotton-top tamarin, five alleles from the owl monkey, three alleles from the long
      haired spider monkey, three alleles from the white-faced saki monkey and two
      alleles from the pygmy marmoset. On the basis of phylogenetic tree analyses, 13
      new DRB alleles were assigned to eight different MHC-DRB lineages. Whereas
      traditional DRB typing via cloning and sequencing provides limited information,
      our new technique provides a simple and relatively rapid way of identifying New
      World monkey MHC-DRB alleles.

PMID- 14714153
TI  - Modeling of basolateral ATP release induced by hypotonic treatment in A6 cells.
AB  - ATP is released from the basolateral membrane of A6 epithelia in response to
      hypotonic treatment. This study addresses the problem of ATP diffusion through
      the permeable supports used to culture the cells. A theoretical analysis of a
      recently introduced experimental protocol is presented and a model of ATP
      diffusion through the compartments of the measuring system is proposed. The model
      provides the ATP profiles near the cell layer and in the measurement chamber.
      Comparison of results from computer simulations and experimental data showed that
      the permeable support introduces a marked delay for ATP diffusion, supporting the
      correlation of apparently time-separated events: the mobilization of Ca(2+) from
      internal stores and release of ATP from the cell. The model is consistent with
      experimental data obtained with the luciferin-luciferase pulse protocol and
      provides an indirect proof of related processes like the closure and opening of
      the lateral interspace that occur after imposing the hyposmotic shock. The
      influence of the pore structure of the permeable support in modulating the
      measured release rates revealed by computer simulation is experimentally
      validated for two types of Anopore filters.

PMID- 14714154
TI  - Location and orientation of Triclosan in phospholipid model membranes.
AB  - Triclosan is a hydrophobic antibacterial agent used in dermatological
      preparations and oral hygiene products. Although the molecular mechanism of
      action of this molecule has been attributed to inhibition of fatty acid
      biosynthesis, earlier work in our laboratories strongly suggested that the
      antibacterial action of Triclosan is mediated at least partly through its
      membranotropic effects. In order to assess its location in phospholipid
      membranes, high-resolution magic-angle spinning natural abundance (13)C NMR of
      Triclosan embedded within egg yolk lecithin model membranes has been used to
      obtain (13)C spin-lattice relaxation times for both Triclosan and lecithin carbon
      atoms in the presence of Gd(3+ )ions. The results indicate that Triclosan is
      localized in the upper region of the phospholipid membrane, its hydroxyl group
      residing in the vicinity of the C = O/C2 carbon atoms of the acyl chain of the
      phospholipid, and the rest of the Triclosan molecule is probably aligned in a
      nearly perpendicular orientation with respect to the phospholipid molecule.
      Intercalation of Triclosan into bacterial cell membranes likely compromises the
      functional integrity of those membranes, thereby accounting for at least some of
      this compound's antibacterial effects.

PMID- 14714155
TI  - Micelle delivery of doxorubicin increases cytotoxicity to prostate carcinoma
      cells.
AB  - The use of doxorubicin as a chemotherapeutic agent is hindered by its toxic side
      effects on the normal cells of the body. The objective of this study was to
      determine if micelle-delivered doxorubicin could increase the effectiveness of
      doxorubicin against prostate carcinoma cells. Rat prostate carcinoma cells
      (MatLu) were cultured under standard conditions. Phosphate-buffered saline (PBS),
      doxorubicin and/or micelle solution (Pluronic 10500 solution) was added to the
      cell suspensions and incubated for 3 h. After incubation, cells were washed
      twice. Analysis consisted of: 1) immediate cell count and 2) proliferation assay
      at 24 and 144 h. After 24 h, samples with micelle-incorporated doxorubicin had
      75% (10% pluronic with 10 microg/ml doxorubicin) and 80% (1% pluronic with 10
      microg/ml doxorubicin) cell proliferation results compared with the control
      group. After 144-h incubation, these same two groups demonstrated cell
      proliferation results of only 30 and 43% of the control group. The in vitro
      cytotoxicity of doxorubicin against prostate carcinoma cells was dramatically
      increased by incorporating the molecule with polymeric micelles.

PMID- 14714156
TI  - Giant cerebellar tuberculoma mimicking a malignant tumour.
AB  - We present a patient with a giant cerebellar tuberculoma which MRI led us to
      believe was a vascular, malignant tumour. Angiography revealed the mass to be
      relatively avascular, but also showed marked narrowing of the posterior
      circulation vessels, suggesting arteritis. Biopsy of the lesion was reported as
      consistent with tuberculoma. We highlight the need to integrate different imaging
      modalities in arriving at a diagnosis of an intracranial mass and discuss
      atypical features of intracranial tuberculomas.

PMID- 14714158
TI  - Imaging in pancreatic infection.
AB  - The most common cause of infection involving the pancreas is complicated
      pancreatitis. Infected necrosis, pancreatic abscess, and infection of pancreatic
      pseudocysts are seen. Diagnostic imaging, in particular, contrast-enhanced
      computed tomography, plays a large role in the identification of the
      complications seen in acute pancreatitis. The imaging findings of the infectious
      complications of pancreatitis is reviewed. Diagnostic imaging also plays a role
      in the diagnosis of infected necrosis and in the percutaneous management of
      pancreatic abscesses and pseudocysts. The imaging findings of pancreatic necrosis
      are usually not sensitive to the presence of co-existent infection. Image-guided
      needle aspiration of the necrotic pancreas can be crucial in the diagnosis of
      infected necrosis. Image-guided placement of percutaneous drainage catheters is a
      nonsurgical alternative for the management of pancreatic abscesses and
      pseudocysts. Image-guided catheter placement and the management of these
      catheters is discussed.

PMID- 14714157
TI  - Internal models underlying grasp can be additively combined.
AB  - Our ability to additively combine two learned internal models was investigated by
      studying the forces people generate when lifting objects with a precision grip.
      Subjects were required to alternately lift two objects of identical physical
      appearance but differing weight. Grip force scaling prior to lift-off was used to
      estimate the output of the internal model associated with each object.
      Appropriate internal models were formed when alternately lifting two objects of
      different weight. The objects were then combined by stacking them one upon the
      other, and the combined object was lifted. Results show that subjects can
      additively combine internal models of object dynamics but the sum is biased by a
      default estimate of the object's weight.

PMID- 14714159
TI  - Management of cholangitis.
AB  - Acute cholangitis remains a life-threatening complication of biliary obstruction,
      particularly in the elderly with comorbid disease or when there is a delay in
      diagnosis and treatment. The initial management consists of fluid resuscitation,
      correction of coagulopathy, and administration of broad-spectrum antibiotics. The
      choice of antibiotics should cover both gram-negative and gram-positive organisms
      associated with cholangitis until the results of a blood culture are available.
      The timing and choice of biliary decompression varies depending on the response
      to antibiotic therapy, the presence of comorbid disease, and the underlying
      cause. Biliary sepsis resolves in most patients with conservative treatment, thus
      allowing time to perform more detailed non-interventional imaging (e.g., spiral
      computed tomography [CT], magnetic resonance cholangiopancreatography [MRCP]) to
      determine the underlying cause and level of biliary obstruction. Those with
      cholangitis who do not respond to conservative therapy will require urgent
      biliary decompression. In patients with choledocholithiasis, endoscopic drainage
      is now the treatment of choice or, if this fails, transhepatic biliary
      decompression is a useful alternative. Various endoscopic options are available
      for managing choledocholithiasis, ranging from endoscopic papillotomy (EP) and
      extraction of stones, to the placement of a biliary drainage system. In patients
      who respond to antibiotic therapy, EP with stone extraction is preferred, while
      in those with ongoing sepsis and multiple large stones, the placement of a stent
      with or without an EP is the safest option. Transhepatic biliary drainage is now
      reserved for failure of endoscopic drainage and for patients with suspected hilar
      cholangiocarcinoma or intrahepatic stones. Surgical biliary decompression is
      seldom required in the emergency setting, but still plays an important role in
      the definitive treatment of the underlying cause.

PMID- 14714160
TI  - Bacterial translocation and its prevention in acute pancreatitis.
AB  - In recent years, bacterial translocation from the gut onto pancreatic necrosis
      has been proposed as the main cause of pancreatic infection and the consequent
      sepsis. Failure of the intestinal barrier, together with bacterial overgrowth due
      to motility changes and immunosuppression, constitute the pathways of the
      continuous pancreatic contamination from bacterial translocation in patients with
      severe acute pancreatitis. Selective decontamination, by using a combination of
      oral and intravenous antibiotics, has been reported to decrease the incidence of
      sepsis and the related mortality. Immunostimulation is another action to be taken
      to enhance the ability of the immune system to prevent bacterial translocation,
      by the entrapment and killing, by enterocytes, of the bacteria trying to
      translocate through the bowel wall. To keep the mucosal barrier function intact
      is one of the main issues in the prevention of bacterial translocation. This
      could be achieved by the adequate delivery of oxygen and nutrient
      supplementation. Enteral nutrition is a key factor, as it has been proven to
      maintain mucosal integrity, along with preventing deterioration of the immune
      function of the intestine.

PMID- 14714161
TI  - Bacterial analysis of infected pancreatic necrosis and its prevention (Symposium
      8: Pancreatobiliary infection (IHPBA)).
AB  - In severe acute pancreatitis, sepsis mainly due to pancreatic or peripancreatic
      infection have emerged as the most serious complications and now accounts for
      more than 80% of deaths. Collective review of organisms associated with secondary
      pancreatic infection in patients with acute pancreatitis has revealed that most
      of them are intestinal flora. Several experimental studies including ours have
      revealed that acute pancreatitis promotes bacterial translocation (BT), which in
      turn leads to infection of the pancreas and septic complications. Prophylactic
      antibiotics given intravenously have been demonstrated to be beneficial in
      reducing the rate of pancreatic infection, but their survival benefit remains
      unclear. We have demonstrated that continuous regional arterial infusion (CRAI)
      of an antibiotic is more effective than intravenous administration in preventing
      pancreatic infection and improving survival, in a canine model of acute
      necrotizing pancreatitis. Our recent experimental study has revealed that CRAI of
      an antibiotic via the superior mesenteric artery (SMA) is effective in mitigating
      intestinal mucosal damage and preventing BT in acute pancreatitis, thereby
      improving survival. BT aggravates pancreatic necrosis and remote organ damage in
      acute pancreatitis, and SMA infusion of antibiotics is effective in preventing BT
      and is practical for clinical use.

PMID- 14714162
TI  - Percutaneous and laparoscopic approaches of radiofrequency ablation treatment for
      liver cancer.
AB  - BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) and microwave coagulation
      therapy (MCT) have been gaining acceptance as a standard method in the management
      strategy of liver cancer, for reasons of minimally invasive techniques and
      effective results. We present our experience of RFA and MCT in patients with
      liver cancer, and analyze retrospectively the advantages and disadvantages of
      both of the percutaneous and laparoscopic approaches. METHODS: Thirty-two
      consecutive patients (23 men and 9 women) with 19 hepatocellular carcinomas
      (HCC), 12 metastatic liver cancers, and recurrent cholangiocellular carcinoma
      (CCC), were enrolled in this study. Out of these 32 patients, as a prior
      laparotomy, 19 underwent hepatectomy, colectomy, gastrectomy or cholecystectomy,
      and 15 were treated with the laparoscopic approach, 17 treated with the
      percutaneous approach, and 2 treated with the combined approach of those two. All
      of these procedures were carried out under general anesthesia with ultrasound
      guidance. Seven and 30 days after these procedures, an assessment helical
      computed tomography was done. RESULTS: No sign of the residual tissues was noted
      in all patients except only one case. CONCLUSIONS: The percutaneous approach was
      thought to be a more practical and less invasive method regardless previous
      laparotomy. For the laparoscopic approach, tumors located at the hepatic surface
      or margin were preferable candidates.

PMID- 14714163
TI  - Donor experience and outcome of pediatric living-related liver transplantation in
      Saudi Arabia.
AB  - BACKGROUND/PURPOSE: The purpose of this article is to present the first series of
      living donation of liver grafts in Saudi Arabia, as well as in the Arab World,
      and to report the morbidity and mortality of the living donors after such
      procedures. METHODS: A retrospective review of the medical charts of 37 living
      donors who were involved in the procedure of living-related liver transplantation
      (LRLT), that took place in Riyadh Armed Forces Hospital in the period between
      November 1998 and July 2002, is conducted. RESULTS: The age of living donors
      ranged between 21 and 41 years, and there were 22 women and 15 men. All donors
      are first-degree relatives, apart from 2 donors who were the cousins of the
      recipients. There was no mortality among the donors. The morbidity was minimal,
      including 3 cases of biliary leakage and 1 of incisional hernia. Of 39 pediatric
      liver transplantations that have been done over the above period, only 2 cases
      had cadaveric liver transplantation and these were excluded from this study. All
      donors had left lateral segment donation, apart from one who had right lobe,
      segments V-VIII donation to a 14-year-old recipient. CONCLUSION: Living donation
      of hepatic graft is a safe procedure for the donors with an excellent outcome.
      Living-related liver transplantation is the optimal treatment for end-stage liver
      disease and the solution for the scarcity of cadaveric liver grafts. The level of
      acceptance of living donation of hepatic grafts among the Saudi people is
      favorable.

PMID- 14714164
TI  - Long-term survival and prognostic factors in the surgical treatment for
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/PURPOSE: We retrospectively investigated the clinicopathologic
      features and outcome of 51 patients who underwent hepatectomy for intrahepatic
      cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the
      potential prognostic factors for long-term survival. METHODS: There were 27 men
      and 24 women, with a mean age of 63.7 years. The surgical procedures were
      extended right or left hepatectomy (15 cases), right or left hepatectomy (19
      cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy
      (7 cases). The macroscopic findings of the excised tumor showed the mass-forming
      (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the
      intraductal growth (IG) type (7 cases). RESULTS: The patients with the MF type
      had a significantly higher incidence of lymph node metastasis (44.8%), as
      compared to those with the PI or IG type (15.0%). Two patients who died of
      hepatic failure during their hospital stay were excluded from this survival
      study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who
      underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The
      patients with the IG type had the best outcome, followed by those with the PI
      type and MF type. The survival rates with or without lymph node metastasis were
      9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively ( P <<
      0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph
      node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%)
      survived for more than 5 years after operation. The gross appearance of these
      tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in
      1. Except for one case with the PI-type tumor, lymph node metastasis was not
      observed. All of the 5-year survivors underwent curative resection and none of
      them had any positive surgical margin. CONCLUSION: Analysis of the
      clinicopathologic factors influencing the survival after surgical treatment
      showed that the macroscopic type, surgical curability, lymph node metastasis,
      tumor size, and cancer-free margin were the most predictive.

PMID- 14714165
TI  - Follow-up problems and changes in obliteration of the residual cystic cavity
      after treatment for hepatic hydatidosis.
AB  - BACKGROUND/PURPOSE: In this prospective open clinical study, we investigated the
      problems that might arise during the obliteration of the residual cavity in
      hepatic hydatidosis. These problems might be related to the duration of the
      obliteration period and to the effects of omentoplasty on the residual cavity.
      METHODS: We operated on 54 hepatic hydatidosis patients with cystodrainage and
      omentoplasty. We followed these patients for a period of 8 years after the
      operation. We used ultrasonography (US) to evaluate the obliteration of the
      cystic cavity; evaluations were made by serological tests as well
      (hemagglutination test, IHA, and IgE radioallergosorbent test, RAST). RESULTS:
      Most of the reductions in the size of the cystic cavity were observed within the
      first 30 days following the operation (69.7%). At the end of the first
      postoperative year, cystic cavity obliteration was not complete in 34 patients,
      and 5 of these cases had positive indirect IHA and IgE RAST tests for
      Echinococcus granulosus. These patients were treated with extension of albendazol
      therapy. In 2 of these 5 patients, obliteration of the cystic cavity was complete
      within 12 months; their serological tests became negative at 15 and 21 months,
      respectively. In the remaining 3 whose serological tests were still positive at
      the end of the first year, obliteration of the cystic cavity was complete by 27,
      33, and 45 months respectively. Of these 3 patients, the tests became negative at
      30 and 52 months for the first 2 patients; the last patient is still
      serologically positive although we have not determined any findings related to
      the recurrence of the cyst. CONCLUSIONS: Omentoplasty is the preferred method in
      the surgical treatment of hepatic hydatidosis. However, we should keep the
      following facts in mind while following these patients with US: the technique can
      be insufficient, the obliteration of the residual cavity takes time and can be
      misdiagnosed as a recurrence, and ultrasonographic appearances can mimic some
      other diseases whether they are benign or malignant. Moreover, follow-up studies
      should be complemented with the serological tests. Thus, all these steps will
      minimize a misdiagnosis and unnecessary reoperations for hepatic hydatidosis.

PMID- 14714166
TI  - A serous oligocystic adenoma of the head of the pancreas successfully treated by
      dome resection and chemocautery: a new approach to serous oligocystic adenoma.
AB  - Serous oligocystic adenoma (SOA) is an extremely rare benign tumor and ill
      demarcated large cyst. We report a case of pancreatic SOA. During abdominal
      ultrasonography (US) for a routine health examination and computed tomography
      (CT), a 69-year-old woman was found to have a 9-cm unilocular cyst located in the
      head of her pancreas. After a 2-year follow up, the cyst was seen to increase in
      size. The results of US, CT, magnetic resonance imaging, endoscopic retrograde
      cholangiopancreatography (ERCP), and angiography led to suspicion of a benign or
      low grade malignancy cystadenoma of the pancreas adjacent to the peripheral
      organs. Fluid analysis and frozen section pathological studies revealed a serous
      oligocystic adenoma with no malignancy. Dome resection, chemocautery, and omental
      filling were performed, and the postoperative course was uneventful. SOAs are
      difficult to diagnose without surgery. When the cyst exists in the head of the
      pancreas, adjacent to the biliary tract, portal system, or visceral vessels, it
      is also difficult to perform complete resection without the threat of morbidity
      or mortality. We have developed a new approach to SOA diagnosis and treatment
      that involves minimally invasive procedures.

PMID- 14714167
TI  - Two cases of hemosuccus pancreaticus in which hemostasis was achieved by
      transcatheter arterial embolization.
AB  - Hemosuccus pancreaticus is a rare complication of chronic pancreatitis. We report
      two cases of hemosuccus pancreaticus in which hemostasis was achieved by
      transcatheter arterial embolization (TAE). The first patient was a 47-year-old
      man with alcoholic chronic pancreatitis. He presented with upper abdominal pain
      and hematemesis. Upper GI endoscopy failed to detect the source of bleeding, but
      computed tomography (CT) showed a hypervascular area about 3 cm in diameter in a
      pseudocyst at the pancreatic tail. Angiography revealed a pseudoaneurysm in the
      caudal pancreatic artery. Hematemesis was considered to be due to rupture of the
      pseudoaneurysm. TAE of the splenic artery was performed selectively, and this
      successfully stopped the bleeding. The second patient was a 52-year-old man with
      alcoholic chronic pancreatitis. He presented with hematemesis. Upper GI endoscopy
      detected bleeding from the papilla of Vater. CT showed hemorrhage in a pseudocyst
      at the pancreatic body. Angiography revealed angiogenesis around the pseudocyst.
      Hematemesis was considered to result from rupture of the pseudoaneurysm. TAE of
      the dorsal pancreatic artery and posterior superior pancreaticoduodenal artery
      was performed and hemostasis was achieved. We conclude that TAE is a minimally
      invasive and highly effective treatment for hemosuccus pancreaticus.

PMID- 14714168
TI  - Anomalous pancreatico-biliary junction and gall bladder cancer in response to
      Matsumoto M, Maruta M, Maeda K, Utsumi T, Sugioka A, Kuroda M (2002) Epithelial
      cyst of the gallbladder associated with adenocarcinoma. J Hepatobiliary Pancreat
      Surg 9:389-392.

PMID- 14714169
TI  - Oxidative stress in a rat model of nephrosis can be quantified by electron spin
      resonance.
AB  - The pathogenesis of nephrotic syndrome is not clear. In this study, we used
      electron spin resonance (ESR) to evaluate levels of reactive oxygen species in
      rats with puromycin aminonucleoside (PAN)-induced nephrosis. Twenty-six Wistar
      rats were divided into four groups: (1) PAN treated, (2) PAN treated and alpha
      tocopherol supplemented, (3) supplemented with alpha-tocopherol only, (4)
      control. On day 9, urinary protein excretion was measured. On day 10, all animals
      were sacrificed with retrograde perfusion via the aorta to obtain renal venous
      perfusates. The signal intensities of ascorbate radicals in the perfusates were
      determined by ESR. After perfusion, the kidneys were isolated and sieved to
      obtain glomeruli for determination of glomerular thiobarbituric acid-reactive
      substance (TBArs) and alpha-tocopherol. Urinary protein excretion by PAN-treated
      rats increased significantly on day 9 and was reduced by alpha-tocopherol
      supplementation. The ascorbate radical intensity and glomerular TBArs level were
      higher in PAN-treated than in control rats and were both suppressed to control
      levels by alpha-tocopherol supplementation. There were positive correlations
      between ascorbate radical intensity and the daily urinary protein, as well as
      between ascorbate radical intensity and the glomerular TBArs level. Hence, it is
      possible to quantify oxidative stress due to PAN nephrosis by ESR. Our findings
      suggest that lipid peroxidation plays an important role in the pathogenesis of
      proteinuria in PAN-treated rats.

PMID- 14714170
TI  - A case of atypical congenital nephrotic syndrome.
AB  - We present a female newborn with the nephrotic syndrome of intrauterine onset and
      a unique set of extrarenal abnormalities, as well as atypical renal lesions. The
      extrarenal anomalies comprised a soft tissue hemangioma in the frontotemporal
      region, unilateral microphthalmia (with persistent hyperplastic corpus vitreous
      and detachment of the retina), and glaucoma in the other eye. Immature glomeruli
      and/or glomeruli with large cellular crescents were found in renal biopsy
      specimens in the 3rd week of life. On autopsy, 7 weeks later, diffuse mesangial
      sclerosis (DMS) was the predominant type of glomerular lesion. In addition,
      dilations of tubules, forming microcysts, as well as clusters of infiltrating
      cells in the interstitium, were found both in renal biopsy and autopsy specimens.
      Although the symptoms observed in our patient did not match any reported in
      association with the known forms of the congenital nephrotic syndrome (CNS), the
      most probable diagnosis seemed to be CNS due to DMS of intrauterine onset, with
      superimposed drug-related tubulointerstitial nephritis.

PMID- 14714171
TI  - Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome and
      anemia.
AB  - The hemolytic uremic syndrome (HUS) is most commonly associated with Escherichia
      coli, but has been associated with other infections such as Streptococcus
      pneumoniae. Pneumococcus-induced HUS carries an increased risk of mortality and
      renal morbidity compared with E. coli-induced HUS. The pneumococcal organism
      produces an enzyme, which can expose an antigen (T-antigen) present on
      erythrocytes, platelets, and glomeruli. Antibodies to the T-antigen, normally
      found in human serum, bind the exposed T-antigen, and the resultant antigen
      antibody reaction (T-activation) can lead to HUS and anemia. Clinicians need to
      be aware to request specific testing when pneumococcus-induced HUS/anemia is
      suspected, as current blood banking techniques do not routinely test for the
      presence of the T-antigen. Once this association is documented, washing all blood
      products and avoiding plasma products, if possible, is recommended.
      Plasmapheresis can be considered for the more critically ill patient. The
      incidence of pneumococcus-induced HUS may be increasing. We report six cases of
      pneumococcus-induced HUS/anemia presenting at our hospital.

PMID- 14714172
TI  - Impact of long-term conventional and organic farming on the diversity of
      arbuscular mycorrhizal fungi.
AB  - Previous work has shown considerably enhanced soil fertility in agroecosystems
      managed by organic farming as compared to conventional farming. Arbuscular
      mycorrhizal fungi (AMF) play a crucial role in nutrient acquisition and soil
      fertility. The objective of this study was to investigate the diversity of AMF in
      the context of a long-term study in which replicated field plots, at a single
      site in Central Europe, had been cultivated for 22 years according to two
      "organic" and two "conventional" farming systems. In the 23rd year, the field
      plots, carrying an 18-month-old grass-clover stand, were examined in two ways
      with respect to AMF diversity. Firstly, AMF spores were isolated and
      morphologically identified from soil samples. The study revealed that the AMF
      spore abundance and species diversity was significantly higher in the organic
      than in the conventional systems. Furthermore, the AMF community differed in the
      conventional and organic systems: Glomus species were similarly abundant in all
      systems but spores of Acaulospora and Scutellospora species were more abundant in
      the organic systems. Secondly, the soils were used to establish AMF-trap cultures
      using a consortium of Plantago lanceolata, Trifolium pratense and Lolium perenne
      as host plants. The AMF spore community developing in the trap cultures differed:
      after 12 months, two species of the Acaulosporaceae (A. paulinae and A. longula)
      were consistently found to account for a large part of the spore community in the
      trap cultures from the organic systems but were found rarely in the ones from the
      conventional systems. The findings show that some AMF species present in natural
      ecosystems are maintained under organic farming but severely depressed under
      conventional farming, indicating a potentially severe loss of ecosystem function
      under conventional farming.

PMID- 14714173
TI  - Insect herbivory in an intact forest understory under experimental CO2
      enrichment.
AB  - Human-induced increases in atmospheric CO(2) concentration have the potential to
      alter the chemical composition of plant tissue, and thereby affect the amount of
      tissue consumed by herbivorous arthropods. At the Duke Forest free-air
      concentration enrichment (FACE) facility in North Carolina (FACTS-1 research
      facility), we measured the amount of leaf tissue damaged by insects and other
      herbivorous arthropods during two growing seasons in a deciduous forest
      understory continuously exposed to ambient (360 microl l(-1)) and elevated
      (approximately 560 microl l(-1)) CO(2) conditions. In 1999, there was a
      significant interaction between CO(2) and species such that winged elm ( Ulmus
      alata) showed lower herbivory in elevated CO(2) plots, whereas red maple (Acer
      rubra) and sweetgum (Liquidambar styraciflua) did not. In 2000, our results did
      not achieve statistical significance but the magnitude of the result was
      consistent with the 1999 results. In 1999 and 2000, we found a decline (10-46%)
      in community-level herbivory in elevated CO(2) plots driven primarily by
      reductions in herbivory on elm. The major contribution to total leaf damage was
      from missing tissue (66% of the damaged tissue), with galls, skeletonized, and
      discolored tissue making smaller contributions. It is unclear whether the decline
      in leaf damage is a result of altered insect populations, altered feeding, or a
      combination. We were not able to quantify insect populations, and our
      measurements did not resolve an effect of elevated CO(2) on leaf chemical
      composition (total nitrogen, carbon, C/N, sugars, phenolics, starch). Despite
      predictions from a large number of single-species studies that herbivory may
      increase under elevated CO(2), we have found a decrease in herbivory in a
      naturally established forest understory exposed to a full suite of insect
      herbivores and their predators.

PMID- 14714174
TI  - Optimal patch residence time in egg parasitoids: innate versus learned estimate
      of patch quality.
AB  - Charnov's marginal value theorem predicts that female parasitoids should exploit
      patches of their hosts until their instantaneous rate of fitness gain reaches a
      marginal value. The consequences of this are that: (1) better patches should be
      exploited for a longer time; (2) as travel time between patches increases, so
      does the patch residence time; and (3) all exploited patches should be reduced to
      the same level of profitability. Patch residence time was measured in an egg
      parasitoid Anaphes victus (Hymenoptera: Mymaridae) when patch quality and travel
      time, approximated here as an increased delay between emergence and patch
      exploitation, varied. As predicted, females stayed longer when patch quality and
      travel time increased. However, the marginal value of fitness gain when females
      left the patch increased with patch quality and decreased with travel time. A.
      victus females appear to base their patch quality estimate on the first patch
      encountered rather than on a fixed innate estimate, as was shown for another egg
      parasitoid Trichogramma brassicae. Such a strategy could be optimal when inter
      generational variability in patch quality is high and within-generational
      variability is low.

PMID- 14714175
TI  - Causal mechanisms underlying host specificity in bat ectoparasites.
AB  - In parasites, host specificity may result either from restricted dispersal
      capacity or from fixed coevolutionary host-parasite adaptations. Knowledge of
      those proximal mechanisms leading to particular host specificity is fundamental
      to understand host-parasite interactions and potential coevolution of parasites
      and hosts. The relative importance of these two mechanisms was quantified through
      infection and cross-infection experiments using mites and bats as a model.
      Monospecific pools of parasitic mites (Spinturnix myoti and S. andegavinus) were
      subjected either to individual bats belonging to their traditional, native bat
      host species, or to another substitute host species within the same bat genus
      (Myotis). The two parasite species reacted differently to these treatments. S.
      myoti exhibited a clear preference for, and had a higher fitness on, its native
      host, Myotis myotis. In contrast, S. andegavinus showed no host choice, although
      its fitness was higher on its native host M. daubentoni. The causal mechanisms
      mediating host specificity can apparently differ within closely related host
      parasite systems.

PMID- 14714176
TI  - Variability in the prevalence of infection and cercarial production in Galba
      truncatula raised on a high-quality diet.
AB  - Two experiments using seven populations of Galba truncatula were carried out to
      analyse the effect of food quality (cos lettuce only, or cos lettuce+Tetraphyll)
      on the characteristics of infections: (1) in a single population of G. truncatula
      infected by one of three digenea (first experiment), and (2) in seven populations
      of G. truncatula differing in their susceptibility to Fasciola hepatica miracidia
      (second experiment). In most groups, food quality did not have a significant
      effect on the survival of snails. The prevalence of infection in five populations
      was significantly higher in snails raised on lettuce+Tetraphyll (first and second
      experiments), whereas it was close to those noted in lettuce only-reared groups
      in the last two populations (second experiment). Despite the higher growth of
      cercariae-shedding snails when raised on the mixed diet, no significant
      differences were noted. Significant effects of parasite species (first
      experiment) and of snail population (second experiment) on the life-spans of
      cercariae-shedding snails were noted, whereas food quality did not influence this
      parameter. Except for a single snail population, cercarial production in groups
      raised on lettuce+Tetraphyll was significantly higher than that in groups on
      lettuce. The variability noted in the prevalence of snail infections and in the
      intensity of cercarial shedding might be explained by differences in the
      susceptibility of snail populations to F. hepatica infections, and/or by the fact
      that Tetraphyll would not have the same appetency for all populations of G.
      truncatula.

PMID- 14714177
TI  - Ultrastructural and cytochemical identification of megasome in Leishmania
      (Leishmania) chagasi.
AB  - The present work showed the presence of a megasome in Leishmania (Leishmania)
      chagasi amastigotes. Transmission electron microscopy analysis of ultrathin
      serial sections and three-dimensional reconstruction allowed visualization of
      large structures in amastigote forms of L. (L.) chagasi and a multivesicular
      tubule-lysosome structure in metacyclic promastigotes. Morphometric data showed
      that the relative volume occupied by the megasome and the multivesicular tubule
      (MVT)-lysosome structures was about 5% and 3.2%, respectively, in amastigotes and
      promastigotes of L. (L.) chagasi. Further characterization of the megasome in L.
      (L.) chagasi amastigotes was carried out by immunolabeling of cysteine
      proteinase, whereas the lysosomal content of amastigotes and promastigotes was
      confirmed by arylsulfatase cytochemistry.

PMID- 14714178
TI  - Transmission electron microscope study of the ultrastructural changes induced in
      the tegument and gut of Fasciola hepatica following in vivo drug treatment with
      clorsulon.
AB  - Using transmission electron microscopy (TEM), both the tegument and gut of
      Fasciola hepatica were examined in an effort to identify and characterise the
      ultrastructural changes induced following treatment with the flukicidal drug
      clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally
      at 8-8.5 weeks post-infection with clorsulon at a concentration of 12.5 mg/kg
      body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation
      and mature flukes recovered from the bile ducts. After 24 h treatment in vivo,
      disruption of the tegumental syncytium was concentrated at the apex of the
      syncytium where a dark band consisting of numerous secretory bodies was present.
      Some blebbing of the apex had also occurred, "open" bodies were present in this
      region and the mitochondria were slightly swollen. In the cell bodies, swelling
      of the mitochondria and their cristae had also occurred and the Golgi complexes
      appeared to be smaller than normal. The disruption seen after 48 h treatment in
      vivo was similar but more severe: the frequency of blebbing had increased, as had
      the number of "open" bodies and the swelling of the mitochondria. Vacuoles had
      begun to appear in the syncytium-both autophagic and electron-lucent-and swelling
      of the mucopolysaccharide masses around the basal infolds had occurred. Lipid
      droplets were observed occasionally. In the cell bodies, autophagic vacuoles had
      begun to appear and swelling of the mitochondria had increased in severity. After
      72 h treatment in vivo, more severe disruption was seen in the tegumental
      syncytium in which widespread swelling and blebbing of the apex was apparent. The
      basal infolds had become very badly swollen in a number of specimens and damage
      to the spines was evident. The mitochondria remained swollen, as did the
      mucopolysaccharide masses around the basal infolds. Lipid droplets were more
      frequently observed in the syncytium. In the tegumental cells, swelling of the
      mitochondria was greater and an increase in the number of autophagic vacuoles was
      apparent. The gut showed signs of disruption after 24 h treatment in vivo, in
      that the surface lamellae were disrupted and a build-up of autophagic vacuoles at
      the apex of the cells had taken place. Swelling of the mitochondria and the
      cisternae of granular endoplasmic reticulum (gER) was evident. There was a
      decrease in the number of secretory bodies. After 48 h treatment in vivo, the
      number of autophagic vacuoles in the gastrodermal cells had increased, the
      mitochondria and gER remained swollen and the disruption seen to the lamellae was
      still evident. In the 72 h-treated specimens, the disruption seen in the
      gastrodermal cells had increased significantly, with severe vacuolation of the
      apical cytoplasm. An increase in the number of autophagic vacuoles was evident,
      the mitochondria and the gER remained swollen and lipid droplets were present in
      the cells.

PMID- 14714179
TI  - Scanning electron microscopic observations on adult Spirocerca lupi (Nematoda:
      Spirurida, Thelaziidae).
AB  - Scanning electron microscopy was used to study the surface ultrastructure of
      adult worms of Spirocerca lupi. At the anterior end of both sexes, the mouth is
      hexagonal, without definite lips. Around the mouth, two pairs of submedian
      cephalic papillae and two lateral amphids are present. There is a pair of lateral
      cervical papillae. At the anterior end of the body, on the ventral side, an
      excretory pore is seen. In the female, the vulva is located anteriorly and the
      tail is blunt, with a pair of subterminal phasmids. The male tail is spiral, with
      four pairs of preanal papillae, a single large median preanal papilla on the
      anterior lip of the cloacal aperture, two pairs of postanal papillae, four pairs
      of tiny papillae near the tip of the tail and two subterminal phasmids. The
      cuticle shows an abnormal tumour-like mass in two cases.

PMID- 14714180
TI  - Factors affecting the component community structure of haemoparasites in common
      voles ( Microtus arvalis) from the Mazury Lake District region of Poland.
AB  - The prevalence and abundance of infections with haemoparasites were studied over
      a 4-year period in Microtus arvalis (common vole, n =321) sampled from fallow
      grassland sites in north-eastern Poland. Total species richness was five
      (prevalence= Haemobartonella sp. 63.9%, Bartonella spp. 27.7%, Babesia microti
      9.0%, Trypanosoma sp. 8.4% and and Hepatozoon lavieri 3.1%) with 76.9% of the
      voles carrying at least one species and a mean infracommunity species richness of
      1.1. Variation in species richness was determined primarily by season and year,
      the interaction of these factors, and that of year with host age. The observed
      frequency distribution of infracommunity species richness did not differ from
      that predicted by a null model, suggesting that there were no marked associations
      between the species. Analyses of prevalence and abundance of infection with each
      species in turn, revealed that overall the principal causes of variation were
      temporal and seasonal, their interaction, and interactions with intrinsic factors
      (age and sex), the latter playing only a minor role in their own right. However,
      the relative importance of these combinations varied and was distinct for each of
      the species in the study. Prevalence data revealed eight sets of two- and three
      way associations between species, mostly dependent to some extent on one of the
      intrinsic and extrinsic factors in the model. Analysis of quantitative
      associations suggested two sets of positive two-way interactions, none of which
      remained after controlling for the effect of extrinsic and intrinsic factors on
      the abundance of each species. These data are discussed in the context of the
      changing ecological profiles in this region of Eastern Europe and, in a wider
      context, in relation to current understanding of the factors that shape component
      community structures of haemoparasites in wild rodents.

PMID- 14714181
TI  - Helminth fauna of Falconiform and Strigiform birds of prey in Galicia, Northwest
      Spain.
AB  - This is a survey of the helminth fauna of 285 individuals of 14 species of birds
      of prey (Falconiformes and Strigiformes) from Galicia (northwest Spain), namely
      Buteo buteo, Accipiter nisus, A. gentilis, Milvus migrans, M. milvus, Pernis
      apivorus, Circus pygargus, Falco tinnunculus, F. peregrinus, F. subbuteo, Tyto
      alba, Strix aluco, Asio otus and Athene noctua. A total of 15 helminth species
      were detected, namely 8 nematodes ( Eucoleus dispar, Capillaria tenuissima,
      Synhimantus laticeps, Microtetrameres sp., Physaloptera alata, Procyrnea
      leptoptera, Hovorkonema variegatum and Porrocaecum angusticolle), 4 cestodes (
      Cladotaenia globifera, Paruterina candelabraria and Mesocestoides sp.), 2
      trematodes ( Neodiplostomum attenuatum and Strigea falconis), and 1
      acanthocephalan ( Centrorhynchus globocaudatus). The helminth communities
      observed were basically similar, although there were marked differences in
      species richness, which was higher in falconiforms (except for A. gentilis) than
      in strigiforms. More specifically, species richness was highest in B. buteo (13
      species), followed by A. nisus (11 species). In the falconiforms, the helminth
      species present generally exhibited a clear relationship with host diet. In the
      strigiforms, by contrast, species richness was lower than expected given the
      host's diet, suggesting that a different explanation is needed.

PMID- 14714182
TI  - Frequencies of inherited organic acidurias and disorders of mitochondrial fatty
      acid transport and oxidation in Germany.
AB  - The lack of epidemiological data on the frequency and/or burden of organic
      acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders
      (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by
      tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten
      potentially treatable OA and mtFATOD was assessed by active nation-wide
      surveillance on cases presenting with clinical symptoms using the German
      Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented
      by a second independent source: 3-monthly inquiries in the metabolic laboratories
      performing secondary selected screening for OA and mtFATOD. Frequency estimates
      for clinically symptomatic cases older than 7 days in a birth cohort of 844,575
      conventionally screened children was compared to the frequency found in a cohort
      of 382,247 screened by MS-MS in Bavaria and Baden-Wurttemberg. The overall
      frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000-1:6,000)
      by MS-MS as compared to 1:23,000 (95% CI 1:36,000-1:17,000) in symptomatic cases
      presenting mainly with metabolic crisis. The contributions of medium-chain acyl
      CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13
      among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically
      symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in
      four patients, was reported for 22/33 clinically symptomatic cases. No clinically
      symptomatic cases were reported from cohorts with screened by MS-MS. CONCLUSION:
      ten potentially treatable organic acidurias and mitochondrial fatty acid
      transport and oxidations disorders were more common than phenylketonuria with
      organic acidurias accounting for 28% of the cases detected by newborn screening
      and 39% of the cases identified on high risk screening. These conditions were
      related to considerable morbidity and mortality. Considerations for their
      inclusion in expanded newborn screening programmes might be warranted.

PMID- 14714183
TI  - Vitamin D intoxication and hypercalcaemia in an infant treated with pamidronate
      infusions.
AB  - Bisphosphonates are used for the treatment of childhood hypercalcaemia,
      especially that due to malignancies. Here we report the use of intravenous
      pamidronate for the treatment of hypercalcaemia due to vitamin D intoxication in
      a 3-month-old infant. Serum calcium levels were normalised without complications.
      CONCLUSION: pamidronate may be used in hypercalcaemia due to vitamin D
      intoxication in paediatric cases resistant to hydration, diuretics or
      corticosteroids.

PMID- 14714184
TI  - Expression of survivin and X chromosome-linked inhibitor of apoptosis protein in
      ameloblastomas.
AB  - To clarify the role of apoptosis in oncogenesis and cytodifferentiation of
      odontogenic epithelium, expression of survivin and X chromosome-linked inhibitor
      of apoptosis protein (XIAP), inhibitor of apoptosis protein (IAP) family
      proteins, was examined in tooth germs and in benign and malignant ameloblastomas
      by means of immunohistochemistry and reverse-transcription polymerase chain
      reaction. Immunoreactivity for survivin and XIAP was detected in developing and
      neoplastic odontogenic epithelium. In tooth germs, survivin expression was
      evident in inner enamel epithelium. Follicular, plexiform and metastasizing
      ameloblastomas showed survivin reactivity chiefly in neoplastic cells neighboring
      the basement membrane, and most neoplastic cells in basal cell and desmoplastic
      ameloblastomas and ameloblastic carcinomas were positive for survivin. Survivin
      mRNA levels were slightly higher in ameloblastomas than in tooth germs,
      suggesting that elevation of survivin expression might be involved in oncogenesis
      of odontogenic epithelium. Immunoreactivity for XIAP was detected in most
      odontogenic epithelial cells in tooth germs and in benign and malignant
      ameloblastomas, and XIAP mRNA levels were significantly higher in follicular
      ameloblastomas than in plexiform ameloblastomas. The expression of survivin and
      XIAP in odontogenic tissues suggests that these IAP family proteins contribute to
      the biological properties of ameloblastomas, such as cell survival,
      proliferation, differentiation and tissue structuring, as well as to cellular
      regulation during tooth development.

PMID- 14714185
TI  - Colon interposition for esophageal replacement: a single-center experience.
AB  - BACKGROUND: Gastric tube interposition has become the method of choice for
      esophageal replacement after esophagectomy. Colon interposition, on the other
      hand, is widely considered to be a method of last resort, associated with high
      morbidity and mortality. The present study reviews our experience with colon
      interposition for esophageal replacement. PATIENTS: Nineteen consecutive patients
      undergoing colon interposition for esophageal replacement between 1 January 1994
      and 31 July 2001 were reviewed. Outcome was compared with international
      publications on colon interposition as well as with our results following gastric
      tube interposition (fundus rotation gastroplasty). RESULTS: Fourteen men and five
      women with a median age of 68 years (range 44-78) underwent colon interposition
      for benign ( n=9) and malignant ( n=10) lesions. Eighteen patients underwent
      trans-hiatal esophagectomy with cervical anastomosis, and one patient underwent
      thoraco-abdominal esophagectomy with intrathoracic anastomosis. Surgical
      morbidity was 36.8% (7/19). Anastomotic insufficiency and fatal mediastinal
      bleeding occurred in one patient each (5.3%). No cases of graft necrosis were
      observed, and no re-operations were necessary. In-hospital mortality was 15.8%
      (3/19), twice due to surgical complications (abdominal sepsis, mediastinal
      bleeding) and once due to pulmonary and cardiac failure. As a late complication,
      four patients (21.1%) developed anastomotic strictures that necessitated repeated
      endoscopic dilatation. CONCLUSIONS: Gastric tube interposition remains the method
      of choice for esophageal replacement. Colon interposition, however, is a valuable
      alternative with a good long-term function. Early mortality, however, remains a
      matter of serious concern.

PMID- 14714186
TI  - Results of surgical treatment for multiple (> or =5 nodules) bi-lobar hepatic
      metastases from colorectal cancer.
AB  - BACKGROUND: The surgery for the treatment of multiple (> or =5) bi-lobar hepatic
      metastases from colorectal cancer is controversial. This retrospective study
      presents our experience in an attempt to develop reasonable treatment guidelines.
      METHOD: One hundred sixty-one consecutive patients who underwent liver resection
      with curative intent were classified into three groups: H1 (unilateral), H2
      (bilateral, < or =4 nodules), or H3 (bilateral, > or =5 nodules). RESULTS: The
      overall cumulative 5-year survival rate was 46.7%. Survival was similar among
      patients with H1, H2, and H3 disease. Thirty-two patients with H3 disease
      underwent hepatectomy: straightforward hepatectomy in 12, portal vein
      embolization (PVE) prior to hepatectomy in eight, two-stage hepatectomy in two,
      and two-stage hepatectomy combined with PVE in ten. Two-stage hepatectomy with or
      without PVE was the standard approach in patients with synchronous liver
      metastases. The operating mortality in hepatectomy for H3 disease was 0%, and the
      morbidity was 15.2%. The overall response rate to neoadjuvant chemotherapy (NAC)
      was 41.7% (5/12). Patients who responded to NAC (n=5) had a better prognosis than
      non-responders (n=7) ( P<0.05). CONCLUSIONS: Extended hepatectomy, including
      preoperative PVE and multi-step hepatectomy, combined with NAC, may result in a
      favourable prognosis, especially in patients who respond to NAC, but further
      studies with more patients are needed to confirm this.

PMID- 14714187
TI  - Long-term results after surgical extraction of subfoveal choroidal neovascular
      membranes with and without haemorrhage in age-related macular degeneration.
AB  - BACKGROUND: Surgical extraction has been suggested as a treatment of choroidal
      neovascular membranes. We demonstrate the long-term results of our patients
      regarding complications, risk of recurrence and development of visual acuity.
      METHODS: We have retrospectively evaluated the charts and re-examined the
      patients who underwent surgical extraction of choroidal neovascular membranes
      (CNV) because of age-related macular degeneration (AMD) between March 1994 and
      December 2000 in the Department of Ophthalmology of the Benjamin Franklin Clinic,
      Berlin. Fifty-two eyes of 49 patients with a minimum follow-up of 12 months after
      pars plana vitrectomy with CNV extraction and SF6-endotamponade were included.
      Initially, in 15% of all eyes the lesions were obscured by intravitreal
      haemorrhage. All visible lesions were located subfoveally. In 40% of all eyes the
      lesion was predominantly classic; 21% of the lesions were predominantly occult
      and 23% of the lesions were comprised of more than 50% haemorrhage. The maximum
      follow-up was 80 months, the mean 46 months. RESULTS: The median initial visual
      acuity was 0.08 (range: hand movements to 0.4) and the median final visual acuity
      was not significantly different at 0.067 (range: non lux to 0.4). A loss of less
      than three lines of visual acuity occurred in 65.4% of our patients. During
      follow-up, 25% of eyes developed a rhegmatogenous retinal detachment and 19.2% of
      all eyes suffered from recurrence of CNV. At the end of the follow-up, three eyes
      (5.8%) suffered from non-treated retinal detachment and three eyes (5.8%) had
      recurrent CNV lesions. All eyes showed a retinal pigment epithelium defect at the
      site of former CNV. CONCLUSION: A stabilisation of visual acuity in individual
      patients with CNV because of AMD can be achieved by surgical extraction, yet the
      defect of the RPE and the risk of complications limit the benefit. We consider
      the surgical extraction of CNV from AMD in patients with low initial visual
      acuity who are not amenable to PDT.

PMID- 14714188
TI  - Conventional buckling surgery or primary vitrectomy with silicone oil tamponade
      in rhegmatogenous retinal detachment with multiple breaks.
AB  - BACKGROUND: There is controversy about the most appropriate operating methods for
      complicated rhegmatogenous retinal detachment (RD) including multiple tears, and
      surgical techniques may be changed according to the preference of the surgeon. In
      this retrospective study, we compared the surgical results of conventional
      buckling surgery and vitrectomy with silicone oil tamponade for rhegmatogenous
      (RD) with multiple breaks. METHODS: Thirty patients who underwent scleral
      buckling surgery (group 1) and 22 patients who underwent pars plana vitrectomy
      with silicone oil tamponade (group 2) as the primary surgery for rhegmatogenous
      RD with multiple breaks were included in this study. The follow-up period was
      longer than 6 months after surgery. The anatomical success rates and
      complications were evaluated for both groups. RESULTS: Retinal reattachment was
      achieved in 24 of 30 eyes (80%) in group 1 and in 20 of 22 eyes (90.9%) in group
      2 after the initial surgery. In group 1, subretinal hemorrhage developed due to
      the drainage of subretinal fluid in 2 eyes (6.6%) intraoperatively. Elevated
      intraocular pressure (3.3%), ocular motility disturbances (13.2%), and
      proliferative vitreoretinopathy (3.3%) were seen in the postoperative period. In
      group 2, iatrogenic breaks (7.3%) and lens damage (9.09%) occurred during the
      operation. Macular pucker (4.5%), postoperative cataract progression (22.7%),
      ocular hypertension (9.09%) and PVR (9.09%) were noted postoperatively.
      CONCLUSIONS: Both surgical procedures can achieve favorable and comparable
      anatomic outcomes in the majority of patients in the treatment of RD with
      multiple breaks. Intra-and postoperative complications are different in the two
      procedures.

PMID- 14714189
TI  - Monitoring the inheritance of heteroplasmy by computer-assisted detection of
      mixed basecalls in the entire human mitochondrial DNA control region.
AB  - The entire mitochondrial DNA control region (approximately 1122 bp) of 270 blood
      samples (135 mother-child pairs) was determined by direct sequencing. Overall,
      135 'generational events' were screened and within these, 20 mother-offspring
      pairs demonstrated more than 1 mtDNA haplotype. In 13 families, differences in
      the haplotypes between mother and offspring were detected in the form of
      heteroplasmic substitutions. Intergenerational comparisons led to the
      identification of three heteroplasmic point mutations and eight heteroplasmic
      length mutations affecting the children only. In two cases, a point heteroplasmy
      of the maternal sequence was resolved to homoplasmy in the corresponding sequence
      of the child. These discordant maternal-offspring haplotypes suggest that the
      shift in the mtDNA haplotype was the result of segregation of a limited maternal
      subpopulation of mtDNA. As technical implement, quality values assigned to
      basecalls were tested for their application in automated point heteroplasmy
      detection.

PMID- 14714190
TI  - Mutations in 14 Y-STR loci among Japanese father-son haplotypes.
AB  - In the present study 161 Japanese father/son haplotype transfers in 147 pedigrees
      were analyzed at 14 Y-STRs with two multiplex PCR-based typing systems. Five
      isolated single repeat mutations were identified at the DYS389I, DYS439, Y-GATA
      H4, DYS389II and DYS391 loci, and a pedigree showing triple alleles at the DYS385
      locus (a duplicate locus) without allelic discrepancy between the father and son
      was also observed. The overall mutation rate estimated across the 14 Y-STRs in
      the Japanese population was 0.22%/locus/meiosis (95% C.I. 0.09-0.51%). This rate
      was not significantly different (p>0.05) from those of autosomal STRs and Y-STRs
      in other populations, including German, Austrian, Polish and Norwegian
      populations. Furthermore, 138 haplotypes were identified in 147 pedigrees with a
      haplotype diversity value of 0.9983. Therefore, a combination of the two systems
      should permit effective analysis with sufficient discriminatory power.

PMID- 14714191
TI  - Radioactive contamination in the upper part of the Techa river: stirring-up of
      bottom sediments and precipitation of suspended particles. Analysis of the data
      obtained in 1949-1951.
AB  - A hydrodynamic model of the upper part of the Techa river was developed on the
      basis of the river valley geometry as well as data of hydrological conditions and
      of the granulometric composition of bottom sediments. The model describes the
      transport of radioactivity by suspended sediments with different granulometric
      compositions (clay, silt) in the early 1950s. It includes the stirring-up of
      bottom sediments and the precipitation of suspended sediments as a function of
      water discharge rate and water level in the investigated part of the river. The
      results allow to specify the development of the river system contamination as a
      result of inflow of suspended sediments contaminated with radionuclides. In the
      period of liquid radioactive waste (LRW) discharges, the water of the Techa river
      contained a large fraction of finely dispersed particles of less than 5 micro m
      diameter. At the site of LRW discharge 80% of the discharged activity was
      adsorbed to these particles. Depending on the water flow, 40-80% of the
      suspensions precipitated at the bottom of subsequent sedimentation reservoirs. A
      total of about 1.6 MCi adsorbed to the suspended particles entered the open
      hydrographic system of the Techa river. The conclusion that the largest part of
      the activity was adsorbed on the suspended particles contradicts the assumption
      in the Techa river dosimetry system, TRDS-2000, that most of the released
      activity entered the Techa river in soluble form. For a correct reconstruction of
      the doses received by the Techa river population it is, therefore, essential to
      consider hydrodynamic models that take into account the transport of
      radionuclides adsorbed on the suspended particles.

PMID- 14714193
TI  - Malolactic bioconversion using a Oenococcus oeni strain for cider production:
      effect of yeast extract supplementation.
AB  - Yeast extract addition to reconstituted apple juice had a positive impact on the
      development of the malolactic starter culture used to ensure malolactic
      fermentation in cider, using active but non-proliferating cells. In this work,
      the reuse of fermentation lees from cider is proposed as an alternative to the
      use of commercial yeast extract products. Malolactic enzymatic assays, both in
      whole cells and cell-free extracts, were carried out to determine the best time
      to harvest cells for use as an inoculum in cider. Cells harvested at the late
      exponential phase, the physiological stage of growth corresponding to the maximum
      values of specific malolactic activity, achieved a good rate of malic acid
      degradation in controlled cider fermentation. Under the laboratory conditions
      used, malic acid degradation rates in the fermentation media turned out to be
      near 2.0 and 2.5 times lower, compared with the rates obtained in whole-cell
      enzymatic assays, as useful data applicable to industrial cider production.

PMID- 14714192
TI  - Isolation, structure, and HIV-1-integrase inhibitory activity of structurally
      diverse fungal metabolites.
AB  - HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition
      is one of the most promising new drug strategies for anti-retroviral therapy,
      with potentially significant advantages over existing therapies. In this report,
      a series of HIV-1 inhibitors isolated from the organic extract of fermentations
      from terrestrial fungi is described. These fungal species, belonging to a variety
      of genera, were collected from throughout the world following the strict
      guidelines of Rio Convention on Biodiversity. The polyketide- and terpenoid
      derived inhibitors are represented by two naphthoquinones, a biphenyl and two
      triphenyls, a benzophenone, four aromatics with or without catechol units, a
      linear aliphatic terpenoid, a diterpenoid, and a sesterterpenoid. These compounds
      inhibited the coupled and strand-transfer reaction of HIV-1 integrase with an
      IC(50) value of 0.5-120 micro M. The bioassay-directed isolation, structure
      elucidation, and HIV-1 inhibitory activity of these compounds are described.

PMID- 14714194
TI  - Intramedullary spinal cord cavernous malformations: report of ten new cases.
AB  - Spinal cord cavernous malformations (SCCM), once thought to be extremely rare,
      have been diagnosed more frequently since the advent of MRI. In addition to the
      six personal cases surgically treated between 1992 and 1993 and already described
      in the literature, the authors report here a further ten cases operated on
      between April 1993 and January 2001. These involved five males and five females
      whose ages at operation ranged from 12 to 69 years. The SCCM were thoracic in
      five patients and cervical in five. In seven cases, the malformations bulged on
      the surface of the pia mater, while in the other three there was subpial
      discoloration due to the presence of hemosiderin. Removal was total in all cases.
      After surgery, two patients presented transient worsening of preoperative
      paraparesis. At follow-up ranging from 2.2 to 9.2 years (mean 5.7), nine patients
      had made complete motor recovery while one, in whom preoperative paraparesis had
      been severe, remained stationary. At least one follow-up MRI investigation was
      performed in each patient 6 to 12 months after operation. As previously reported,
      the authors confirm that the treatment of choice for symptomatic SCCM is total
      surgical excision in order to avoid recurrences and the possibility of further
      hemorrhage. Surgical outcome combines low mortality with a high probability of
      functional recovery, especially when paraparesis is not severe and of relatively
      recent onset.

PMID- 14714195
TI  - Whole exon 5 and intron 5 replaced by RHCE in DVa(Hus).
AB  - The DVa(Hus) was previously investigated through cDNA analysis, which revealed an
      RHD-CE(5)-D hybrid allele. However, the 5' and 3' breakpoints remain unknown. In
      this article, gene recombinations between the RHD and RHCE alleles were
      investigated by a combination approach of a sequence-specific primer PCR (PCR
      SSP) and an RHD full-length coding region sequencing method on two Chinese
      subjects with weak D phenotypes. The hybrid Rhesus box of each individual was
      also investigated through an established PCR-based method. As a result, two
      partial D phenotypes, DVa(Hus) and DVI type III, were identified, each carrying
      one hybrid RHD-CE-D allele. The two samples were also serotyped with Rh phontypes
      of DccEe and DCcee, respectively. Other sequencing analyses of the DVaHus sample
      showed that the sequence of intron 4 is identical with RHD, whereas the whole
      sequence of exon 5 and intron 5 is identical with RHCE except for seven
      polymorphisms in the intron 5. We may concluded that in the case of this Chinese
      DVa(Hus), the whole exon 5 and complete intron 5 of a total segment of 1801
      nucleotides were replaced by RHCE suggesting that the breakpoints of the replaced
      region are the 5' end of the exon 5 and the 3' end of the intron 5.

PMID- 14714197
TI  - Caries prevention programs for groups: out of fashion or up to date?
AB  - After a caries decline of about 80% in children in Western Europe and other
      industrialized countries, there should be critical debate about the best way for
      future caries prevention. Multiple fluoride use played an important role in
      caries reductions achieved in the 1980s and 1990s, but it also resulted in a
      polarization of lesion distribution in young people: the majority consists of low
      caries or even lesion-free individuals, while a minority is a so-called high
      caries risk group which seems not to be open to preventive programs. Recent
      studies indicate that frequent fluoride applications (>6 times/year) in
      conjunction with effective plaque removal can be a successful approach for
      effective future caries prevention in high caries risk groups. Health promotion
      programs that are merely educational and do not provide fluoride do not seem to
      be effective. Alternatively, preventive measures could be performed at home or in
      a private practice, but only minimal compliance is reached in high risk groups
      compared with out-reaching group programs. Thus, group programs are instrumental
      in providing effective and efficient caries-preventive measures in children. The
      more expensive time of a dental practice team should be limited to procedures
      where costly equipment is needed (professional tooth cleaning, sealants, etc.).
      For efficient caries prevention, measures formerly targeted specifically at
      either populations, groups, or individuals should be remodeled and aimed to
      interact in order to achieve optimal oral health in children at a reasonable
      cost.

PMID- 14714196
TI  - Regional odontodysplasia: a review of the literature and report of four cases.
AB  - Regional odontodysplasia (RO) is a rare dental anomaly involving both dentitions,
      mostly teeth of one quadrant. The characteristic findings are discolored soft
      teeth accompanied by gingivitis, swelling or abscess. Enamel and dentin are
      hypomineralised and hypoplastic, so that the 'ghost teeth' appear shadowy in
      radiographs with wide pulp chambers. The etiology is unknown. Epidemiological
      data is rare; 138 cases of RO have been published to date and reports on
      ultrastructure are few. An analysis of published cases of RO in the international
      literature is presented. The sex ratio of females to males was 1.7:1. The age at
      the time of diagnosis ranged between 4 and 23 years. The maxilla was more often
      affected (maxilla to mandible ratio 1.6:1). In 67 patients the deciduous and
      permanent dentitions were affected (47.1%). In 129 cases, affected teeth lay side
      by side. Missing tooth development was observed in 10.7%. Failure of tooth
      eruption of RO teeth occurred in 39.7%. In addition, four cases with RO which
      were collected over a period of more than 25 years are presented. Ultrastructural
      findings of one specimen are demonstrated.

PMID- 14714198
TI  - Mechanistic studies of 1-aminocyclopropane-1-carboxylic acid oxidase: single
      turnover reaction.
AB  - The final step in the biosynthesis of the plant hormone ethylene is catalyzed by
      the non-heme iron-containing enzyme 1-aminocyclopropane-1-carboxylic acid (ACC)
      oxidase (ACCO). ACC is oxidized at the expense of O(2) to yield ethylene, HCN,
      CO(2), and two waters. Continuous turnover of ACCO requires the presence of
      ascorbate and HCO(3)(-) (or an alternative form), but the roles played by these
      reagents, the order of substrate addition, and the mechanism of oxygen activation
      are controversial. Here these issues are addressed by development of the first
      functional single turnover system for ACCO. It is shown that 0.35 mol
      ethylene/mol Fe(II)ACCO is produced when the enzyme is combined with ACC and O(2)
      in the presence of HCO(3)(-) but in the absence of ascorbate. Thus, ascorbate is
      not required for O(2) activation or product formation. Little product is observed
      in the absence of HCO(3)(-), demonstrating the essential role of this reagent. By
      monitoring the EPR spectrum of the sample during single turnover, it is shown
      that the active site Fe(II) oxidizes to Fe(III) during the single turnover. This
      suggests that the electrons needed for catalysis can be derived from a fraction
      of the initial Fe(II)ACCO instead of ascorbate. Addition of ascorbate at 10% of
      its K(m) value significantly accelerates both iron oxidation and ethylene
      formation, suggesting a novel high-affinity effector role for this reagent. This
      role can be partially mimicked by a non-redox-active ascorbate analog. A
      mechanism is proposed that begins with ACC and O(2) binding, iron oxidation, and
      one-electron reduction to form a peroxy intermediate. Breakdown of this
      intermediate, perhaps by HCO(3)(-)-mediated proton transfer, is proposed to yield
      a high-valent iron species, which is the true oxidizing reagent for the bound
      ACC.

PMID- 14714199
TI  - Fusicoccin induces in plant cells a programmed cell death showing apoptotic
      features.
AB  - Programmed cell death plays a pivotal role in several developmental processes of
      plants and it is involved in the response to environmental stresses and in the
      defense mechanisms against pathogen attack. It has not yet been defined which
      part of the death signalling mechanism and which molecules involved in programmed
      cell death are common to animals and plants. In this paper we show that
      fusicoccin, a well-known phytotoxin, induces a strong acceleration in the
      appearance of Evans Blue-stainable (dead) cells in sycamore (Acer pseudoplatanus
      L.) cultures. This fusicoccin-induced cell death shows aspects common to the form
      of animal programmed cell death termed apoptosis: i.e., cell shrinkage, changes
      in nucleus morphology, increase in DNA fragmentation detectable by a specific
      immunological reaction, and presence of oligonucleosomal-size fragments
      (laddering) in DNA gel electrophoresis. Since fusicoccin has a well-identified
      molecular target, the plasma membrane H(+)-ATPase, and thoroughly investigated
      physiological effects, this toxin appears to be a useful tool to study the
      transduction of death signals leading to programmed cell death in plants.

PMID- 14714200
TI  - Impact of hypoosmotic challenges on spongy architecture of the cytoplasm of the
      giant marine alga Valonia utricularis.
AB  - The ultrastructure of the several micrometers thick cytoplasmic layer of the
      giant marine alga Valonia utricularis displays characteristics which are
      apparently linked with the capability of this alga to regulate turgor pressure.
      Transmission and scanning electron microscopy of cells prefixed in different
      ways, including a protocol that allows prefixation of the alga in a turgescent
      state, revealed a highly dendritic network of cytoplasmic strands connecting and
      enveloping the chloroplasts and the nuclei. Innumerable vacuolar entities are
      embedded in the network, giving the cytoplasm a spongy appearance. Vacuolar
      perfusion of turgor-pressure-clamped cells with prefixation solution containing
      tannic acid presented evidence that these vacuolar entities together with the
      huge central vacuole form a large unstirred continuum. In contrast to the
      tonoplast, the plasmalemma followed smoothly the lining of the cell wall, even at
      the numerous cell wall ingrowths. Sucrose, but not polyethylene glycol 6000,
      induced chloroplast clustering. Acute hypoosmotic treatment (established by
      reduction of external NaCl or by replacement of part of the external NaCl by
      equivalent osmotic concentrations of sucrose or polyethylene glycol 6000)
      resulted in a local relocation of the chloroplasts and cytoplasm towards the
      central vacuole. This effect did not occur when the relatively low reflection
      coefficients of these two osmolytes were taken into account. The increase in
      spacing between the spongy cytoplasm and the plasmalemma by chloroplast
      relocation (viewed by confocal laser scanning microscopy) was associated with a
      speckled appearance of the affected surface area under the light microscope. As
      indicated by electron microscopy, hypoosmotically induced chloroplast relocation
      resulted from disproportionate swelling of the vacuolar entities located close to
      the plasmalemma. The cytoskeleton in the cytoplasm and the mucopolysaccharide
      network in the central vacuole apparently resisted swelling of these
      compartments. This finding has the important consequence that relevant
      hydrostatic pressure gradients can be built up throughout the entire multifolded
      vacuolar space. This gradient could represent the trigger for turgor pressure
      regulation which is manifested electrically first in the tonoplast.

PMID- 14714201
TI  - Combined use of confocal laser scanning microscopy and transmission electron
      microscopy for visualisation of identical cells processed by cryotechniques.
AB  - Successive visualisation of identical plant cells by light and electron
      microscopy is reported. For this purpose segments of pea and barley leaves were
      prepared by high-pressure freezing, freeze-substitution, and low-temperature
      embedding. The use of Safranin O during low-temperature dehydration allowed, on
      one hand, staining of all cellular components as investigated by confocal laser
      scanning microscopy and, on the other hand, excellent ultrastructural and
      antigenic preservation. A newly constructed specimen holder enabled precise
      relocation of the target cells for electron microscopic investigations.
      Transmission electron microscopy and immunohistochemistry revealed that during
      the whole procedure the ultrastructure of the cells as well as the antigenicity
      of cell constituents were preserved.

PMID- 14714202
TI  - Regulation of Brassica rapa chloroplast proliferation in vivo and in cultured
      leaf disks.
AB  - To understand the regulatory mechanisms of chloroplast proliferation, chloroplast
      replication was studied in cultured leaf disks cut from plants of 25 species. In
      leaf disks from Brassica rapa var. perviridis, the number of chloroplasts per
      cell increased remarkably in culture. We examined chloroplast replication in this
      plant in vivo and in culture media with and without benzyladenine, a cytokinin.
      In whole plants, leaf cells undergo two phases from leaf emergence to full
      expansion: an early proliferative stage, in which mitosis occurs, and a
      differential stage after mitosis has diminished. During the proliferative stage,
      chloroplast replication keeps pace with cell division. In the differential phase,
      cell division ceases but chloroplast replication continues for two or three more
      cycles, with the number of chloroplasts per cell reaching about 60. In the leaf
      disks, the number of chloroplasts per cell increased from about 18 to 300 without
      benzyladenine, and to over 600 with benzyladenine, indicating that this cytokinin
      enhances chloroplast replication in cultured tissue. We also studied changes in
      ploidy and cell volume between in vivo cells and cells grown in culture with and
      without benzyladenine. Ploidy and cell volume increased in a manner very similar
      to that of the number of chloroplasts, suggesting a relationship between these
      phenomena.

PMID- 14714203
TI  - Localization of calcium in the pericarp cells of tomato fruits during the
      development of blossom-end rot.
AB  - Blossom-end rot (BER) of tomato ( Lycopersicon esculentum) fruits is considered
      to be a physiological disorder caused by calcium deficiency. We attempted to
      clarify the localization of calcium in the pericarp cells and the ultrastructural
      changes during the development of BER. Calcium precipitates were observed as
      electron-dense deposits by an antimonate precipitation method. Some calcium
      precipitates were localized in the cytosol, nucleus, plastids, and vacuoles at an
      early developmental stage of normal fruits. Calcium precipitates were increased
      markedly on the plasma membrane during the rapid-fruit-growth stage compared with
      their level at the early stage. Cell collapse occurred in the water-soaked region
      at the rapid-fruit-growth stage in BER fruits. There were no visible calcium
      precipitates on the traces of plasma membrane near the cell wall of the collapsed
      cells. The amount of calcium precipitates on plasma membranes near collapsed
      cells was smaller than that in the cells of normal fruits and normal parts of BER
      fruits, and the amount on cells near collapsed cells was small. The amount of
      calcium precipitates on the plasma membranes increased as the distance from
      collapsed cells increased. On the other hand, calcium precipitates were visible
      normally in the cytosol, organelles, and vacuoles and even traces of them in
      collapsed cells. The distribution pattern of the calcium precipitates on the
      plasma membrane was thus considerably different between normal and BER fruits. On
      the basis of these observations, we concluded that calcium deficiency in plasma
      membranes caused cell collapses in BER tomato fruits.

PMID- 14714204
TI  - Roles of actin-depleted zone and preprophase band in determining the division
      site of higher-plant cells, a tobacco BY-2 cell line expressing GFP-tubulin.
AB  - The mode of cytokinesis, especially in determining the site of cell division, is
      not well understood in higher-plant cells. The division site appears to be
      predicted by the preprophase band of microtubules that develop with the
      phragmosome, an intracellular structure of the cytoplasm suspending the nucleus
      and the mitotic apparatus in the center. As the preprophase band disappears
      during mitosis, it is thought to leave some form of "memory" on the plasma
      membrane to guide the growth of the new cell plate at cytokinesis. However, the
      intrinsic nature of this "memory" remains to be clarified. In addition to
      microtubules, microfilaments also dynamically change forms during cell cycle
      transition from the late G2 to the early G1 phase. We have studied the
      relationships between microtubules and microfilaments in tobacco BY-2 cells and
      transgenic BY-2 cells expressing a fusion protein of green-fluorescent protein
      and tubulin. At the late G2 phase, microfilaments colocalize with the preprophase
      band of microtubules. However, an actin-depleted zone which appears at late
      prometaphase is observed around the chromosomes, especially at metaphase, but
      also throughout anaphase. To study the functions of the actin-depleted zone, we
      disrupted the microfilament structures with bistheonellide A, a novel macrolide
      that depolymerizes microfilaments very rapidly even at low concentrations. The
      division planes became disorganized when the drug was added to synchronized BY-2
      cells before the appearance of the actin-depleted zone. In contrast, the division
      planes appeared smooth, as in control cells, when the drug was added after the
      appearance of the actin-depleted zone. These results suggest that the actin
      depleted zone may participate in the demarcation of the division site at the
      final stage of cell division in higher plants.

PMID- 14714205
TI  - Events during the first four rounds of mitosis establish three developmental
      domains in the syncytial endosperm of Arabidopsis thaliana.
AB  - Endosperm begins development as a single fertilized cell that undergoes many
      rounds of mitosis without cytokinesis resulting in a syncytium. The multinucleate
      cytoplasm is organized by nucleus-based radial microtubule systems into nuclear
      cytoplasmic domains. When microtubules are organized into mitotic spindles, the
      integrity of the common cytoplasm is maintained by an unaltered network of
      filamentous actin. The first four rounds of mitosis result in the establishment
      of three developmental domains within the common cytoplasm. The spindles of the
      first two rounds of mitosis are oriented parallel to the long axis of the central
      cell, resulting in four nuclear-cytoplasmic domains in a filamentous arrangement.
      A switch in spindle orientation occurs in the third round of mitosis; all four
      spindles are oriented perpendicular to the long axis resulting in eight nuclear
      cytoplasmic domains arranged in two adjacent files. Whereas the first three
      rounds of mitosis are synchronous, the fourth occurs as a wave of successive
      mitoses that begins at the micropylar pole. By the 16-nuclei stage, differences
      in nuclear shape, cytoskeletal arrays, and cytoplasmic characteristics mark the
      differentiation of the syncytium into micropylar, central, and chalazal
      developmental chambers. Nuclei in the micropylar chamber are fusiform and
      sheathed by parallel microtubules that flare from their tips, while those in the
      central and chalazal chambers are spherical. Nuclei in the central chamber are
      surrounded by radial microtubule systems, while those in the chalaza are enmeshed
      in a reticulum of microtubules. Whereas the cytoplasm in both micropylar and
      chalazal chambers is dense and nearly nonvacuolate, the syncytium in the central
      chamber consists of a single layer of evenly spaced nuclear-cytoplasmic domains
      surrounding a large central vacuole.

PMID- 14714206
TI  - Characteristics of trajectory in the migration of Amoeba proteus.
AB  - We investigated the behavior of migration of Amoeba proteus in an isotropic
      environment. We found that the trajectory in the migration of A. proteus is
      smooth in the observation time of 500-1000 s, but its migration every second (the
      cell velocity) on the trajectory randomly changes. Stochastic analysis of the
      cell velocity and the turn angle of the trajectory has shown that the histograms
      of the both variables well fit to Gaussian curves. Supposing a simple model
      equation for the cell motion, we have estimated the motive force of the migrating
      cell, which is of the order of piconewton. Furthermore, we have found that the
      cell velocity and the turn angle have a negative cross-correlation coefficient,
      which suggests that the amoeba explores better environment by changing frequently
      its migrating direction at a low speed and it moves rectilinearly to the best
      environment at a high speed. On the other hand, the model equation has simulated
      the negative correlation between the cell velocity and the turn angle. This
      indicates that the apparently rational behavior comes from intrinsic
      characteristics in the dynamical system where the motive force is not torquelike.

PMID- 14714207
TI  - Actins from plant and animal sources tend not to form heteropolymers in vitro and
      function differently in plant cells.
AB  - Pollen and skeletal muscle actins were purified and labeled with fluorescent dyes
      that have different emission wavelengths. Observation by electron microscopy
      shows that the fluorescent actins are capable to polymerize into filamentous
      actin in vitro, bind to myosin S-1 fragments, and have a critical concentration
      similar to unlabeled actin, indicating that they are functionally active. The
      globular actins from two sources were mixed and polymerized by the addition of
      ATP and salts. The copolymerization experiment shows that when excited by light
      of the appropriate wavelength, both red actin filaments (pollen actin) and green
      actin filaments (muscle actin) can be visualized under the microscope, but no
      filaments exhibiting both green and red colors are detected. Furthermore,
      coprecipitations of labeled pollen actin with unlabeled pollen and skeletal
      muscle actin were performed. Measurements of fluorescent intensity show that the
      amount of labeled pollen actin precipitating with pollen actin was much higher
      than that with skeletal muscle actin, indicating that pollen and muscle actin
      tend not to form heteropolymers. Injection of labeled pollen actin into living
      stamen hair cells results in the formation of normal actin filaments in
      transvacuolar strands and the cortical cytoplasm. In contrast, labeled skeletal
      muscle actin has detrimental effects on the cellular architecture. The results
      from coinjection of the actin-disrupting reagent cytochalasin D with pollen actin
      show that overexpression of pollen actin prolongs the displacement of the nucleus
      and facilitates the recovery of the nuclear position, actin filament
      architecture, and transvacuolar strands. However, muscle actin perturbs actin
      filaments when injected into stamen hair cells. Moreover, nuclear displacement
      occurs more rapidly when cytochalasin D and muscle actin are coinjected into the
      cell. It is concluded that actins from plant and animal sources behave
      differently in vitro and in vivo and that they are functionally not
      interchangeable.

PMID- 14714208
TI  - A myosin inhibitor impairs auxin-induced cell division.
AB  - The role of myosins for auxin-induced cell division was probed using the
      inhibitor 2,3-butanedione monoxime in the tobacco cell line VBI-0, where cell
      elongation and division are axially aligned under the control of auxin. A
      morphometric analysis revealed that cell division is blocked in a dose-dependent
      manner, whereas cell expansion continued. In addition, the polarity of terminal
      cells was impaired resulting in malformed, pear-shaped cells. Early effects of
      the inhibitor are aberrant features of the cytoarchitecture including a block of
      vesicle transport, a diffuse broadening of cross walls, and the disorganization
      of the actin cytoskeleton. The findings are discussed with respect to a possible
      role of myosins as link between vesicle flow and signal control of cell division.

PMID- 14714209
TI  - Antisense transgenesis of tobacco with a flax pectin methylesterase affects
      pollen ornamentation.
AB  - Antisense transgenesis of tobacco (Nicotiana tabacum) with a partial flax (Linum
      usitatissimum L.) pectin methylesterase (Lupme3) cDNA sequence yielded plants
      with altered pollen content. Moreover, the characteristically sculptured cell
      wall surrounding the pollen grains was modified in transgenic tobacco plants: the
      wavy ornamentation was dramatically reduced, suggesting the involvement of the
      demethylation of pectin in the pollen cell wall-specific structure. Germination
      of pollen was decreased and the pollen tube surface aspect was also different in
      transgenic plants.

PMID- 14714210
TI  - Apical growth and mitosis are independent processes in Aspergillus nidulans.
AB  - It is well established that cytoplasmic microtubules are depolymerized during
      nuclear division and reassembled as mitotic microtubules. Mounting evidence
      showing that cytoplasmic microtubules were also involved in apical growth of
      fungal hyphae posed the question of whether apical growth became disrupted during
      nuclear division. We conducted simultaneous observations of mitosis (fluorescence
      microscopy) and apical growth (phase-contrast microscopy) in single hyphae of
      Aspergillus nidulans to determine if the key parameters of apical growth
      (elongation rate and Spitzenkorper behavior) were affected during mitosis. To
      visualize nuclei during mitosis, we used a strain of A. nidulans, SRS27, in which
      nuclei are labeled with the green-fluorescent protein. To reveal the
      Spitzenkorper and measure growth with utmost precision, we used computer-enhanced
      videomicroscopy. Our analysis showed that there is no disruption of apical growth
      during mitosis. There was no decrease in the rate of hyphal elongation or any
      alteration in Spitzenkorper presence before, during, or after mitosis. Our
      findings suggest that apical growth and mitosis do not compete for internal
      cellular resources. Presumably, the population of cytoplasmic microtubules
      involved in apical growth operates independently of that involved in mitosis.

PMID- 14714211
TI  - Experimental excitotoxicity provokes oxidative damage in mice brain and
      attenuation by extract of Asparagus racemosus.
AB  - Excitotoxicity and oxidative stress are the major mechanisms of neuronal cell
      death in neurodegenerative disorders that occurs in both Alzheimer's and
      Parkinson's diseases. Reactive oxygen species (ROS) that are generated
      extracellularly and intracellularly by various mechanisms are among the major
      risk factors that initiate and promote neurodegeneration.Therefore, it is
      important to find the compound which retard or reverse the neuronal injury. We
      designed this study to investigate the potential of extract of Asparagus
      racemosus (AR) against kainic acid (KA)-induced hippocampal and striatal neuronal
      damage. The dose of AR extract given to experimental animals was based on the
      evaluation of its total antioxidant activity. Extract of AR displayed potent
      reductant of Fe(3+). The excitotoxic lesion in brain was produced by intra
      hippocampal and intra-striatal injections of kainic acid (KA; 0.25 microg in a
      volume of 0.5 microl) to ketamine and xylazine (200 and 2 mg/kg b.w.
      respectively) anesthetized mice. The results showed impairment of hippocampus and
      striatal regions of brain after KA injection marked by an increase in lipid
      peroxidation and protein carbonyl content and decline in glutathione peroxidase
      (GPx) activity and reduced glutathione (GSH) content. The AR extract supplemented
      mice displayed an improvement in GPx activity and GSH content and reduction in
      membranal lipid peroxidation and protein carbonyl. We show that the minimizing
      effect of AR extract on oxidative damage in addition to the elevation of GPx
      activity and GSH content could eventually result in protective effect on the KA
      induced excitotoxicity.

PMID- 14714212
TI  - Functional recovery of locus coeruleus noradrenergic neurons after DSP-4 lesion:
      effects on dopamine levels and neuroleptic induced-parkinsonian symptoms in rats.
AB  - Noradrenaline has been shown to control dopamine turnover and release in rat
      brain. Noradrenergic lesion with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine
      (DSP-4) decreases dopamine release in the striatum and enhances catalepsy in
      experimental models of Parkinson's disease. However, in due course, sprouting of
      remaining noradrenergic axons, to compensate for the decreased noradrenaline is
      said to occur in specific brain regions. Though this is to some extent
      understood, the longstanding effects of noradrenergic lesion on dopaminergic
      neurons of the basal ganglia and in Parkinsonian behavior is not known. Here the
      question is addressed, whether locus coeruleus lesion with DSP-4 in rats alters
      dopamine concentration of the basal ganglia and influences Parkinsonian behavior
      in a long term (6 months). Parkinsonian behavior was assessed by catalepsy and
      activity cage after challenging with subthreshold dose of haloperidol (0.2
      mg/kg), on 7, 30, 90, 120 and 180 days after DSP-4 lesion. The concentrations of
      noradrenaline and dopamine and its metabolites were estimated by HPLC. 6 months
      after DSP-4 lesion, increased concentration of noradrenaline was found in
      prefrontal cortex and hippocampus. Other regions remain unaffected. The
      concentration of dopamine remained unchanged. However, dopamine turnover appeared
      to be increased in prefrontal cortex and reduced in striatum and nucleus
      accumbens. Catalepsy and hypoactivity were observed in DSP-4 lesioned animals
      after haloperidol challenge on 7th, 30th and 60th day. Though dopamine turnover
      was reduced after 6 months in the striatum, haloperidol-induced catalepsy was not
      observed after 60 days. These results indicate a gradual functional recovery,
      perhaps hyperinnervation of noradrenergic neurons after DSP-4 treatment and the
      reversal of its effects on dopaminergic neurons and on Parkinsonian symptoms.

PMID- 14714213
TI  - Quantitation of 5HT3 receptors in forebrain of serotonin transporter deficient
      mice.
AB  - Mice deficient in the serotonin transporter (5HTT) display highly elevated
      extracellular 5HT levels. 5HT exerts ist effects via at least fourteen different
      cloned 5HT receptors located pre- and postsynaptically. In contrast to the other
      5HT receptors, the 5HT3 receptor is a ionotropic receptor with ligand-gated
      cation channel function. Since G-protein-coupled 5HT receptors show extensive
      adaptive changes in 5HTT-deficient mice, we investigated whether 5HT3 receptors
      are also altered in these mice. Using quantitative autoradiography, we found that
      5HT3 receptors are upregulated in frontal cortex (+46%), parietal cortex (+42%),
      and in stratum oriens of the CA3 region of the hippocampus (+18%) of 5HTT
      knockout mice. Changes in 5HT3 receptor mRNA expression, as determined by
      quantitative in situ hybridisation, were less pronounced. The adaptive changes of
      5HT3 receptor expression constitute a part of the complex regulatory pattern of
      5HT receptors in 5HTT knockout mice.

PMID- 14714214
TI  - Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected
      mesencephalic dopaminergic cells.
AB  - Ginsenosides Rb1 and Rg1 are the main active ingredients of Panax ginseng C.A.
      Meyer (Araliaceae). They appear to exert protection against ischaemia and anoxic
      damage in animal models, suggesting an antioxidative and cytoprotective role. In
      our study, primary cultures from embryonic mouse mesencephalon are applied to
      examine the effects of these two ginsenosides on neuritic growth of dopaminergic
      cells and their survival affected by 1-methyl-4-phenylpyridinium-iodide (MPP(+)).
      Ginsenoside Rb1 (at 10 microM) enhanced the survival of dopaminergic neurons by
      19% compared to untreated control. MPP(+) (at 1 microM) significantly reduced the
      number of dopaminergic neurons and severely affected neuronal processes. Both
      ginsenosides counteracted these degenerations and significantly protected lengths
      and numbers of neurites of TH(+) cells. Both compounds however could not prevent
      the cell loss caused by MPP(+). Our study thus indicates partial neurotrophic and
      neuroprotective actions of ginsenosides Rb1 and Rg1 in dopaminergic cell culture.

PMID- 14714215
TI  - Parkin mutation associated parkinsonism and cognitive decline, comparison to
      early onset Parkinson's disease.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) have cognitive changes
      resulting, presumably, from a progressive disruption of the functional integrity
      of frontostriatal circuitry. OBJECTIVE: To assess the cognitive state of two
      brothers with early onset autosomal recessive (EO-AR) parkinsonism and a large
      deletion in the parkin gene, and to compare it to that of patients with sporadic
      young onset PD (YOPD). METHOD: Two brothers with parkinsonism and deletion of
      axons 4-6 of the parkin gene (ages 51, 55 years; duration of symptoms, 22, 29
      years respectively) and 4 randomly selected patients with YOPD (mean age 47.8+/
      4.9 years; mean duration of symptoms, 11.5+/-1.9 years) were administered a
      neuropsychological battery at "on" state. We assessed global cognitive state
      using the Mini-Mental State Examination (MMSE), orientation, attention, memory,
      language, ideational praxis, constructive praxis and executive functions
      (shifting aptitude, verbal fluency, sequencing). RESULTS: The older of the two
      brothers with EO-AR parkinsonism had dementia according to DSM IV criteria, and
      MMSE score of 24, whereas the other had normal global cognitive status with mild
      cognitive changes (MMSE=29). The older brother had impaired memory tasks. Storage
      and retrieval capacities were defective on both immediate and delayed recalls,
      naming, constructional praxis, selective attention, shifting aptitude and
      phonemic and semantic fluency were also affected. The younger brother had
      difficulties in retrieval on delayed recall, selective attention, phonetic
      fluency, shifting aptitude and sequencing. This neuropsychological profile
      clearly differs from that of the YOPD patients, none of whom displayed cognitive
      dysfunction. CONCLUSIONS: Our patients with parkin mutation performed poorly on
      neuropsychological tests compared to those with YOPD. This difference could
      reflect the longer disease duration or the nature of the degenerative process.

PMID- 14714216
TI  - Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET
      study shows increased D2 receptors.
AB  - We investigated the integrity of striatal dopaminergic system in seven patients
      with dopa-responsive dystonia (DRD). Dopamine transporter function ([(11)C]CFT)
      and D1 ([(11)C]NNC 756) and D2 receptors ([(11)C]raclopride) were studied in same
      patients using positron emission tomography. Compared to age-adjusted control
      values the dopamine D2 receptor availability was increased in DRD. The mean age
      adjusted [(11)C]raclopride uptake was 116% of the control mean in the putamen (p
      = 0.004) and 114% in the caudate nucleus (p = 0.007). The mean [(11)C]NNC 756
      uptake was not different between DRD patients and controls, the age-adjusted
      uptake in DRD being 93% of mean control value in the putamen (p = 0.20) and 95%
      in the caudate nucleus (p = 0.40). The dopamine transporter binding was not
      altered. The [(11)C]CFT uptake in DRD was 96% of the control value in the putamen
      (p = 0.64), and 95% in the caudate nucleus (p = 0.44). In conclusion, striatal
      dopamine D2 receptors availability is increased in DRD whereas dopamine D1
      receptors and dopamine transporter ligand binding is unchanged. The pattern of
      changes in striatal dopaminergic system in DRD is different from that reported in
      juvenile Parkinson's disease. The increased D2 receptor availability may be due
      to reduced competition by endogenous dopamine or a compensatory response to
      dopamine deficiency, or both.

PMID- 14714217
TI  - Vascular risk and genetics of sporadic late-onset Alzheimer's disease.
AB  - In recent years, it is becoming apparent that genes may play an important role in
      the development of late-onset Alzheimer's disease (LOAD), and genetic studies
      could unravel new clues. Based on a growing vascular hypothesis for the
      pathogenesis of LOAD and other dementias, there is increasing interest for
      environmental and genetic vascular factors. Polymorphisms in different
      susceptibility genes already implicated in vascular disease risk are now also
      being suggested as possible genetic markers for increased risk of developing
      LOAD; however, many of these studies have shown conflicting results. Thus far,
      the apolipoprotein E (APOE) gene seems to be the only vascular susceptibility
      factor that is agreed to play a role in the multifactorial pathogenesis of AD
      although emerging genetic and biological evidence is now strengthening the case
      for additional inclusion of angiotensin I-converting enzyme 1 (ACE1) into this
      category. This review will focus on the current knowledge on genetic and
      nongenetic vascular factors likely to be involved in LOAD, with special emphasis
      placed on the APOE and ACE1 genes.

PMID- 14714218
TI  - Hippocampal volume and cell proliferation after acute and chronic clozapine or
      haloperidol treatment.
AB  - The dentate gyrus contains progenitor cells possessing the capacity to
      proliferate until and throughout adulthood. There is little information about the
      influence of antipsychotics on cell proliferation. To address this, we
      investigated the influence of acute and chronic haloperidol and clozapine
      treatment on the total number of newly dividing cells and hippocampal volume
      using an animal model with doses equivalent to the therapeutic range in humans.
      Rats were treated with either acute or 28 days haloperidol (1 mg/kg i.p. or 1,5
      mg/kg/day oral) or clozapine (30 mg/kg i.p. or 45 mg/kg/day oral). After BrdU
      injection, immunohistochemistry was performed in serial hippocampal brain
      sections. Total BrdU-labeled cell number and hippocampus volume were estimated
      using stereological methods. Neither neuroleptic altered total number of newly
      dividing cells in the dentate gyrus. In contrast, chronic haloperidol treatment
      did increase total hippocampal volume suggesting that haloperidol alters
      neuroplastic processes or glial morphology rather than cell proliferation.

PMID- 14714219
TI  - Association of 5-HT1B receptor gene and antisocial behavior in alcoholism.
AB  - The 5-HT1B receptor gene has been postulated to play a modulatory role in alcohol
      consumption and alcohol dependence, and was considered a candidate gene for
      alcoholism. More recently, the association of the 5-HT receptor gene polymorphism
      and antisocial personality traits in alcoholism has been discussed. This possible
      association was studied using material from our gene bank for alcoholism. The
      research instruments used to phenotype patients were partly adopted from the US
      Collaborative Study on the Genetics of Alcoholism (COGA) which include anxiety-
      and depression-related scales from personality inventories such as the
      temperament and character inventory (TCI), the NEO-Five-Factor Inventory (NEO
      FFI) and the Minnesota Multiphase Personality Inventory (MMPI-2). Based on the
      examination of 164 alcoholic subjects, an association was found between a lower
      frequency of the 5-HT 1B 861C allele, antisocial personality traits and conduct
      disorder in alcohol-dependent subjects. Adult antisocial personality occurred
      more often in males than females. Possible implications of these findings are
      discussed.

PMID- 14714220
TI  - Expression of tissue factor mRNA and invasion of blood vessels by tumor cells in
      non-small cell lung cancer.
AB  - PURPOSE: Tissue factor (TF), an initiator of the extrinsic coagulation cascade,
      is also expressed in a wide range of cancer cells and plays an important role in
      cancer progression and metastasis, as well as in processes independent of the
      blood coagulation pathway. For example, by acting as an adhesion molecule
      enabling tissue invasion, TF may play a key role in the metastatic process and
      angiogenesis in non-small cell lung cancer (NSCLC). METHODS: To further
      investigate the role of TF on tumor cell invasion in NSCLC, we measured the TF
      mRNA expression in the tumors of 42 NSCLC patients using real-time quantitative
      reverse transcription - polymerase chain reaction carried out in a LightCycler.
      We then compared the TF mRNA expression with histological evidence of invasion of
      blood and lymphatic vessels by tumor cells. RESULTS: Although there was no
      significant relationship between the TF mRNA expression and the invasion of
      lymphatic vessels, the TF mRNA expression was significantly higher in tumors that
      invaded blood vessels (Log(10) TF mRNA/GAPDH mRNA = 2.16 +/- 0.18) than in those
      that did not (1.59 +/- 0.16; P = 0.03). CONCLUSION: These results suggest that TF
      plays a major role in blood vessel invasion by tumor cells in NSCLC.

PMID- 14714221
TI  - Intermittent pneumatic compression is effective in preventing symptomatic
      pulmonary embolism after thoracic surgery.
AB  - PURPOSE: Postoperative pulmonary embolism (PE) remains a fatal complication even
      in thoracic surgery. We have used intermittent pneumatic compression for the
      prophylaxis of postoperative PE since 1998, and herein examined its
      effectiveness. METHODS: Seven hundred and six patients, whose medical records
      showed use/no use of pneumatic compression for prophylaxis of PE, underwent
      general thoracic surgery in our department from December 1995 to December 2000.
      Their clinical records were reviewed, and variables were compared between
      patients who experienced clinically apparent PE and patients who did not have PE.
      RESULTS: Three hundred and forty-four patients did not receive any prophylactic
      treatment, and 7 of these (2.0%) experienced postoperative PE. Three hundred and
      sixty-two patients received prophylactic pneumatic compression and none of these
      developed PE. There was a statistical correlation between the occurrence of PE
      and the application of pneumatic compression (Chi(2)-test, P = 0.006). Six of the
      seven patients with PE were operated on in the right decubitus position, and the
      operative position and the prevalence of PE was also significantly correlated
      (Chi(2)-test, P = 0.024). Other factors, such as age, sex, operative time,
      duration until patients became fully ambulatory, body mass index, and character
      of the disease, did not have significant correlation with the occurrence of PE.
      CONCLUSIONS: Pneumatic compression was found to effectively prevent postoperative
      PE. The right decubitus position is considered to be a risk factor for the
      development of postoperative PE in thoracic surgery.

PMID- 14714222
TI  - Comparative study of the effect on clinical outcome of the use of an open circuit
      and the use of a closed circuit in cardiopulmonary bypass for a graft replacement
      of the descending thoracic or thoracoabdominal aorta.
AB  - PURPOSE: We studied the benefits of reduced systemic heparinization in a heparin
      coated cardiopulmonary bypass (CPB) system for graft replacement of the
      descending thoracic (TA) or thoracoabdominal aorta (TAA). METHODS: Fifty-five
      patients were assigned to two groups: one group in which closed CPB circuits with
      reduced heparinization by elimination of the hard shell reservoir were used
      (group A, n = 36) and one group in which open circuits with full heparinization
      were used (group B, n = 19). RESULTS: The transfusion requirement tended to be
      greater as the duration of CPB increased, even in group A. The incidences of
      renal dysfunction in two groups were not significantly different. Only the
      incidence of pulmonary dysfunction was significantly higher in group B. A
      reduction of systemic heparinization had no benefit for perioperative bleeding.
      In the TAA operation, the total amount of hemorrhaging in group A was greater
      than that in group B, but the difference was not significant. CONCLUSIONS: No
      beneficial effects of the use of heparin-coated CPB circuits on the amount of
      perioperative bleeding and postoperative organ damage, including renal
      dysfunction, were found in this study. However, our findings suggest that it may
      be better to avoid the use of closed CPB circuits in operations with a prolonged
      duration of CPB, such as a TAA operation.

PMID- 14714223
TI  - Surgical experience of full root replacement with freestyle bioprosthesis:
      indications, surgical technique, and results.
AB  - PURPOSE: We examined the postoperative clinical results and hemodynamic
      performance of full root replacement using a freestyle stentless bioprosthesis
      performed in patients with severe aortic stenosis or aortic root disease.
      METHODS: We performed 17 full root replacements with a stentless bioprosthesis.
      The mean age of the patients was 73.9 +/- 4.1 years, ranging from 63 to 81, and
      35% were male. The operative indications were aortic stenosis (AS) in 9 patients,
      aortic stenosis with regurgitation (ASR) in 4, and aortic regurgitation due to
      aortic root dissection or annuloaortic ectasia in 4. RESULTS: The valve size of
      the freestyle bioprosthesis was 25.1 +/- 2.6 mm, ranging from 21 to 29 mm. There
      were no early or late mortalities. No postoperative aortic regurgitation was
      found. In the 13 patients undergoing an operation for AS or ASR, peak pressure
      gradients were 8.5 +/- 4.2 and 8.4 +/- 5.2 mmHg, and LV mass indices were 159.4
      +/- 19.0 and 106.9 +/- 22.6 g/m(2), as determined by echocardiography at 1 and 10
      months after operation, respectively. CONCLUSION: Full root replacement with
      stentless bioprosthesis is a suitable procedure for patients of advanced age with
      severe AS, aortic root dissection, or annuloaortic ectasia, because of its
      superior hemodynamics.

PMID- 14714224
TI  - Autologous blood donation before elective off-pump coronary artery bypass
      grafting.
AB  - PURPOSE: Preoperative autologous blood donation reduces exposure to homologous
      blood transfusions in cardiac surgery. The purpose of this study was to ascertain
      the volume of predonated autologous blood needed to avoid homologous blood
      transfusion in scheduled off-pump coronary artery bypass grafting (off-pump
      CABG). METHODS: Fifty-six patients underwent scheduled off-pump CABG between
      January 1999 and December 2000. These patients all donated either 400 ml (group
      1, n = 33) or 800 ml (group 2, n = 23) of autologous blood before operation.
      These patients donated at a rate of 400 ml per week. All patients were given an
      equal volume of saline solution at the time of autologous donation. RESULTS:
      There were no significant differences in the mean age, mean body weight, mean
      preoperative hematocrit values, mean graft number, or mean volume of
      intraoperative blood loss between groups 1 and 2. There was a significant
      difference in the mean postoperative day-7 hematocrit value (33.6% +/- 1.3% vs
      39.3% +/- 1.3%, P << 0.05). The rates of avoiding homologous blood transfusion
      were 63.6% in group 1 and 100% in group 2 ( P << 0.05). CONCLUSIONS: Autologous
      blood transfusion is effective for reducing the homologous blood requirement. We
      believe that an 800-ml predonation is sufficient to avoid homologous blood
      transfusion in scheduled off-pump CABG; furthermore, patients with cardiovascular
      disease, including severe coronary artery disease, should be administered saline
      along with the blood donation.

PMID- 14714225
TI  - Effects of intestinal surgery on pulmonary, glomerular, and intestinal
      permeability, and its relation to the hemodynamics and oxidative stress.
AB  - PURPOSE: To investigate the pattern of changes of gut mucosal, glomerular, and
      pulmonary permeability in response to major resectional intestinal surgery, and
      to evaluate whether these changes are related to oxidative stress. METHODS: Eight
      patients undergoing elective intestinal surgery. Lactulose/mannitol ratio (LMR),
      urinary albumin/creatinine ratio (MACR), and extravascular lung water and its
      ratio to intrathoracic blood volume (EVLW/ITBV) were measured preoperatively and
      at different time points postsurgery. The oxidant/antioxidant balance was
      assessed by measuring thiobarbituric acid-reactive species, reduced glutathione,
      plasma total antioxidant capacity, superoxide dismutase, and glutathione
      peroxidase. RESULTS: Uncomplicated intestinal surgery was associated with early
      increase in LMR and MACR. The EVLW/ITBV ratio increased, but still remained
      within the normal range. The amount of EVLW was not affected. While renal
      permeability changes resolved rapidly, increased intestinal permeability
      persisted longer postoperatively. There was no evidence for any marked
      disturbances in the oxidant/antioxidant balance. CONCLUSIONS: This pilot study
      indicated that a moderate increase in gut and renal permeability, even in the
      absence of clinical sequelae, is an early feature of uncomplicated intestinal
      surgical trauma. These alterations are not accompanied by any clinically
      detectable changes in pulmonary permeability.

PMID- 14714226
TI  - Survival and recurrence after a sphincter-saving resection and abdominoperineal
      resection for adenocarcinoma of the rectum at or below the peritoneal reflection:
      a multivariate analysis.
AB  - PURPOSE: The purpose of this study was to determine whether the type of operation
      [sphincter-saving resection (SSR) or abdominoperineal resection (APR)] for
      primary adenocarcinoma of the rectum at or below the peritoneal reflection
      affects survival and recurrence after curative surgery. METHODS: This
      retrospective study included 184 patients who underwent curative surgery achieved
      by the following two types of operation between 1989 and 1998: (1) SSR ( n = 116
      patients) including a low anterior resection with either double-stapling
      technique ( n = 86) or transanal coloanal anastomosis ( n = 30); (2) APR ( n =
      91). The outcome factors evaluated were survival and tumor recurrence. Both
      univariate and corrected (multivariate Cox's and logistic regression) analyses
      were used to evaluate the data. The median follow-up was 47.4 months for patients
      alive at study conclusion. RESULTS: Disease-free and disease-specific survivals,
      and the frequency and location of recurrence after surgery did not differ between
      the two types of operations. Multivariate analyses showed that the type of
      operation was not a significant independent variable in predicting disease-free
      survival or in the development of both local and distant recurrences after
      surgery. In addition, tumor-related factors (stage or histologic grade) were
      significant predictors of the outcome after surgery. CONCLUSIONS: The type of
      operation (SSR or APR) did not affect the survival or recurrence after a curative
      resection for adenocarcinoma of the rectum at or below the peritoneal reflection.

PMID- 14714227
TI  - Angiogenesis inhibitor TNP-470 can suppress hepatocellular carcinoma growth
      without retarding liver regeneration after partial hepatectomy.
AB  - PURPOSE: We investigated the suppressive effect of the angiogenesis inhibitor TNP
      470 on accelerated hepatocellular carcinoma (HCC) growth in the regenerating
      liver. METHODS: After 70% partial hepatectomy (PH), AH-130 cells were injected
      into the portal vein of Donryu rats. A control group was given the vehicle only,
      and the treated group was given 10 mg/kg TNP-470 subcutaneously every second day,
      from 24 h after tumor implantation, seven times. On day 14, tumor growth was
      evaluated by the number of foci on the liver surface, liver weight, and the
      microvessel density of the tumor. RESULTS: The number of foci was significantly
      less in the treated group (116.5 +/- 103.1) than in the control group (319.3 +/-
      223.1) ( P < 0.05), as was microvessel density, which was 31.3 +/- 14.0/mm2 in
      the treated group and 61.2 +/- 18.9/mm2 in the control group ( P < 0.05). The
      liver tended to weigh less in the treated group (12.15 +/- 1.28 g) than in the
      control group (15.22 +/- 5.35 g). We also assessed whether TNP-470 retards liver
      regeneration. Seven days after 70% PH, the liver weight in the treated group was
      similar to that in the control group. Total bilirubin, serum glutamic oxaloacetic
      transaminase, and serum glutamic pyruvic transaminase were not higher in the
      treated group than in the control group. CONCLUSION: TNP-470 can suppress HCC
      growth without retarding liver regeneration after PH.

PMID- 14714228
TI  - Ultrastructural changes in the contralateral lung tissue following unilateral
      lung ischemia: an experimental study in rabbits.
AB  - PURPOSE: To investigate the acute ultrastructural changes that may occur in the
      contralateral nonischemic lung tissue after unilateral ischemia of a lung in a
      rabbit model. METHODS: The animals were divided into three main groups of eight;
      namely, a 2-h procedure group, a 4-h procedure group, and an 8-h procedure group.
      Each of these groups was further divided into two subgroups of four rabbits each;
      namely, a control group, given a sham operation without any ischemic insult, and
      an ischemia group, in which the main pulmonary arteries, the pulmonary veins, and
      the main bronchi of the left lungs were ligated after thoracotomy. Tissue samples
      were taken from the left and right lungs to examine the ultrastructural changes
      after 2, 4, and 8 h of ischemia. Each sample was given a semiquantitative
      histological injury score. Statistical analysis was done by the Mann-Whitney U
      test. RESULTS: Contralateral ultrastructural damage, evident by heterochromatin
      in the nuclei, mitochondrial degeneration, cisternal widening of the endoplasmic
      reticulum, increased lipid droplets, and lysosomes, was determined by electron
      microscopy after unilateral lung ischemia. The contralateral lung injury was
      significantly correlated with the duration of ischemia. CONCLUSIONS: Unilateral
      lung ischemia affected the bilateral lungs in a rabbit model. Therefore, in
      operations such as single-lung transplantation, pulmonectomy, or lobectomy, if
      the procedure is unnecessarily prolonged, the contralateral lung may be damaged,
      which could seriously affect the prognosis of the patient.

PMID- 14714229
TI  - Pulmonary benign metastasizing leiomyoma from the uterus in a postmenopausal
      woman: report of a case.
AB  - We report a case of pulmonary benign metastasizing leiomyoma (BML) from the
      uterus in a 77-year-old woman. The patient presented for investigation of
      multiple pulmonary nodules on a routine chest roentgenogram. Because a
      preoperative diagnosis could not be made, the largest tumor, 3.5 cm in diameter,
      was resected from the right lower lobe, and histological examination confirmed
      BML. She had undergone hysterectomy with oophorectomy for uterine leiomyomas 12
      years earlier, at the age of 65. The microscopic findings of the lung tumor were
      similar to those of the uterine leiomyoma, and both lesions were histologically
      benign. Although this disease is considered to be hormone-dependent, metastasis
      was found in this elderly postmenopausal woman whose tumor was negative for
      estrogen receptor.

PMID- 14714230
TI  - Huge localized fibrous tumor of the pleura resembling a mediastinal tumor: report
      of a case.
AB  - A 67-year-old man was admitted to our hospital because of an abnormal chest
      echoic lesion detected incidentally by echocardiography. A chest roentgenogram
      showed the presence of a giant mass, and computed tomography of the chest
      confirmed the presence of a mass with a nonhomogeneous density in the left
      mediastinum, just adjacent to the left ventricle of the heart. Percutaneous
      aspiration cytology of the mass showed benign fibrous cells and a small amount of
      lymphocytes. The preoperative diagnosis of the tumor suggested a thymoma, and the
      patient underwent a thoracotomy. A pedunculated tumor arose from the visceral
      pleura of the left upper lobe of the lung, and it was capsulated within the
      pleura. The tumor measured 15 x 12 x 8 cm in size and it was successfully
      resected. The pathological diagnosis of the tumor was benign localized fibrous
      tumor of the pleura.

PMID- 14714231
TI  - Esophageal intramural pseudodiverticulosis treated by balloon dilatation: report
      of a case.
AB  - A 72-year-old man presented with a 17-year history of dysphagia, which had
      gradually become worse in recent months. A barium esophagogram showed stenosis of
      the upper thoracic esophagus with multiple tiny flask-shaped outpouchings along
      the region of stenosis. Based on this characteristic appearance, we diagnosed
      esophageal intramural pseudodiverticulosis. He underwent successful balloon
      dilatation of the stenosis and his dysphagia resolved. Dynamic esophagography
      showed improved passage through the esophagus. He has been well and not suffering
      from dysphagia for 4 years since the balloon dilatation.

PMID- 14714232
TI  - Ileal perforation in a patient with high spinal cord injury: report of a case.
AB  - Assessing abdominal complications in patients who have previously suffered high
      spinal cord injury is very difficult because the resultant loss of sensory,
      motor, and reflux function of the abdominal wall can mask the typical signs of
      acute abdomen such as tenderness, muscle rigidity, and peritoneal rebound pain.
      We recently diagnosed a small intestinal perforation in a 77-year-old man with a
      C6-7 spinal cord injury sustained 14 years earlier. The patient was correctly
      diagnosed as having an acute abdominal condition, despite palsy of abdominal wall
      sensation. An emergency laparotomy was done and a 40-cm length of affected ileum,
      about 180 cm distal to the Treitz ligament, including a 1-cm perforation, was
      resected, followed by an end-to-end anastomosis. We report this case to raise
      awareness of the need for appropriate diagnosis and early surgical treatment of
      abdominal complications in spinal-cord-injured patients.

PMID- 14714233
TI  - Refractory ulcerative colitis complicated by a cytomegaloviral infection
      requiring surgery: report of a case.
AB  - Cytomegalovirus (CMV) infection has been reported to be a cause of refractory
      ulcerative colitis (UC). We herein report a case of refractory ulcerative colitis
      complicated by CMV infection requiring surgery. A 22-year-old man was admitted to
      our hospital with lower abdominal pain and bloody diarrhea. Under a diagnosis of
      acute UC, he was treated with prednisone 60 mg/day and sulfasalazine. Since his
      symptoms appeared to improve, the prednisone dosage was gradually reduced to 20
      mg/day. After 5 months, he had an unexpected flare-up with fever and fresh anal
      bleeding. Colonoscopy demonstrated a punched out ulcer in the sigmoid colon.
      Biopsies by colonoscopy revealed cytomegalic inclusion bodies. Serologic and
      immunologic studies also suggested a recent CMV infection. Under a diagnosis of
      intractable UC complicated by a CMV infection, ganciclovir therapy was carried
      out, and the steroid therapy was tapered. Although the serum antigenemia became
      negative after the antiviral therapy, follow-up colonoscopy confirmed the severe
      stenosis after the punched-out ulcer healed completely. Since his symptoms did
      not improve, it was necessary to perform an elective proctocolectomy despite
      antiviral therapy. He was discharged with an uneventful postoperative course. It
      is important to recognize CMV colitis as a complication of inflammatory bowel
      disease, particularly in severe steroid-resistant colitis. Furthermore, in cases
      which fail to respond to antiviral treatment, the patient may ultimately require
      surgery.

PMID- 14714234
TI  - Minilaparotomy approach for removal of a large colonic lipoma: report of two
      cases.
AB  - A minimally invasive surgical approach should be employed to resect symptomatic
      colonic lipomas whenever possible. We report two cases of large colonic lipomas
      that were successfully removed using a minimally invasive minilaparotomy
      approach. Patient 1 was a 53-year-old man with a 3.8-cm symptomatic submucosal
      lipoma in the ascending colon and patient 2 was a 57-year-old woman with a 4.2-cm
      symptomatic submucosal lipoma in the transverse colon. Both lipomas were
      successfully removed through a 5-7-cm minilaparotomy. Normal bowel function
      returned quickly without any postoperative complications. These case reports
      demonstrate that the minilaparotomy approach is a suitable alternative to
      conventional laparotomy to remove a large colonic lipoma.

PMID- 14714235
TI  - Unusual atrophic change after repeated arterial therapy for hepatocellular
      carcinoma: report of a case.
AB  - We report the case of a 45-year-old man with advanced hepatocellular carcinoma
      (HCC) who was able to undergo radical surgery after repeated transarterial
      therapy. Transarterial chemoembolization was repeated three times, and
      thereafter, transarterial infusion chemotherapy using Lipiodol was performed on
      the right hepatic artery. Because notable atrophy of the right lobe and
      compensated hypertrophy of the left lobe were detected after this therapy, an
      extended right lobectomy could be performed. Histologically, the HCC showed
      complete necrosis. The remarkable atrophic change of the right lobe was thought
      to be due to an obstruction of the right portal veins by the spread of
      inflammation around the bile duct necrosis, in addition to the narrowing of the
      hepatic artery. A thorough understanding of this phenomenon and the development
      of methods to clinically apply it in the treatment of cancer patients may thus
      lead to an increase in the percentage of resectable cases of advanced HCC.

PMID- 14714236
TI  - Primary gas gangrene of the pancreas: report of a case.
AB  - Spontaneous gas gangrene of the pancreas, caused by an infection of Clostridium
      perfringens, is an extremely rare but severe form of acute pancreatitis. A 67
      year-old man complaining of severe epigastric pain with diffuse guarding
      underwent an emergency laparotomy. During surgery, hemorrhagic pancreatic
      necrosis was observed with a large amount of peripancreatic gas. Cultures
      demonstrated C. perfringens. The identification of hemolysis and the accumulation
      of peripancreatic gas on computed tomography, which were both caused by an
      infection of C. perfringens, led us to make a diagnosis of clostridial infection
      of the pancreas.

PMID- 14714237
TI  - Brain death due to abdominal compartment syndrome caused by massive venous
      bleeding in a patient with a stable pelvic fracture: report of a case.
AB  - We report a rare case in which abdominal compartment syndrome resulting from
      venous hemorrhaging developed in a patient with stable pelvic fractures,
      resulting in a fatal outcome. An 84-year-old man with mild pelvic fractures
      developed hypovolemic shock and underwent transcatheter arterial embolization. He
      became hemodynamically stable after the procedure, but became hypotensive for the
      second time 11 h after admission. Urinary bladder pressure rose to 32 mmHg from 4
      7 mmHg. Rebleeding from the pelvis with the development of abdominal compartment
      syndrome was suspected. Repeated transcatheter arterial embolization and
      laparotomy were performed; however, 1 min into the procedure, both pupils
      symmetrically dilated and the light reflex disappeared. This case suggests that
      brain death can sometimes occur due to abdominal compartment syndrome.

PMID- 14714238
TI  - Carcinoid tumor of the kidney presenting as a large abdominal mass: report of a
      case.
AB  - Carcinoid tumors are known to occur frequently in the gastrointestinal tract and
      they can develop in nearly every organ system. However, a carcinoid tumor of the
      kidney is an extremely rare entity and only 38 cases have been reported in the
      English literature. We herein describe the 39th case of primary renal carcinoid
      tumor, found in a young Japanese woman 2 months after delivery. The pathologic
      similarities of our case with those of previously reported cases are briefly
      reviewed together with some aspects of clinical features and prognostic factors
      of this rare disease.

PMID- 14714239
TI  - Large solitary fibrous tumor of the retroperitoneum: report of a case.
AB  - We report an unusual case of a large solitary fibrous tumor (SFT) in the
      retroperitoneum. A 53-year-old man was referred to our hospital for surgical
      treatment of a swelling in the right flank with dull pain. Abdominal computed
      tomography (CT) and echograms showed a large encapsulated tumor compressing the
      right kidney and liver. At laparotomy, the tumor was found to be encapsulated but
      fixed to the capsule of the right kidney within a small area. Therefore, complete
      removal was achieved. The resected specimen was an encapsulated elastic hard
      tumor, 14 x 13 x 10 cm in size. Immunohistochemical studies revealed reactivity
      for CD34 and vimentin, but no staining for keratin, S-100, or alpha-smooth muscle
      actin, confirming a diagnosis of SFT. Although SFT is usually associated with a
      favorable prognosis, close follow-up is recommended because of the limited
      information on its long-term behavior.

PMID- 14714240
TI  - Successful coil embolization for spontaneous arterial rupture in association with
      Ehlers-Danlos syndrome type IV: report of a case.
AB  - When a patient with Ehlers-Danlos syndrome (EDS) presents with a vascular
      emergency, performing life-saving surgery can be difficult because of the
      profound fragility of the arterial tissue. We report the case of a 27-year-old
      woman with EDS in whom a spontaneous arterial rupture was successfully treated
      with transcatheter embolization. The patient was brought to our hospital in
      shock, with left lower abdominal pain. She had been diagnosed with EDS type IV
      following a colonic rupture 8 years earlier. An emergency angiogram revealed
      rupture of the left external iliac artery. The active bleeding was managed by
      transarterial embolization of the ruptured artery using stainless steel coils,
      which took 30 min to achieve. The patient has not suffered any further vascular
      complications during the year since this procedure. Transcatheter coil
      embolization may be a reliable option for treating sudden arterial rupture in
      patients with this syndrome.

PMID- 14714241
TI  - A dynamic investigation of the burst fracture process using a combined
      experimental and finite element approach.
AB  - Spinal burst fractures account for about 15% of spinal injuries and, because of
      their predominance in the younger population, there are large associated social
      and healthcare costs. Although several experimental studies have investigated the
      burst fracture process, little work has been undertaken using computational
      methods. The aim of this study was to develop a finite element model of the
      fracture process and, in combination with experimental data, gain a better
      understanding of the fracture event and mechanism of injury. Experimental tests
      were undertaken to simulate the burst fracture process in a bovine spine model.
      After impact, each specimen was dissected and the severity of fracture assessed.
      Two of the specimens tested at the highest impact rate were also dynamically
      filmed during the impact. A finite element model, based on CT data of an
      experimental specimen, was constructed and appropriate high strain rate material
      properties assigned to each component. Dynamic validation was undertaken by
      comparison with high-speed video data of an experimental impact. The model was
      used to determine the mechanism of fracture and the postfracture impact of the
      bony fragment onto the spinal cord. The dissection of the experimental specimens
      showed burst fractures of increasing severity with increasing impact energy. The
      finite element model demonstrated that a high tensile strain region was generated
      in the posterior of the vertebral body due to the interaction of the articular
      processes. The region of highest strain corresponded well with the experimental
      specimens. A second simulation was used to analyse the fragment projection into
      the spinal canal following fracture. The results showed that the posterior
      longitudinal ligament became stretched and at higher energies the spinal cord and
      the dura mater were compressed by the fragment. These structures deformed to a
      maximum level before forcing the fragment back towards the vertebral body. The
      final position of the fragment did not therefore represent the maximum dynamic
      canal occlusion.

PMID- 14714242
TI  - Prediction of fusion and importance of radiological variables for the outcome of
      anterior cervical decompression and fusion.
AB  - In a prospective randomised study with a 2-year follow-up, 103 patients were
      randomised to anterior cervical decompression and fusion (ACDF) with a cervical
      carbon-fibre intervertebral fusion cage (CIFC) or the Cloward procedure (CP). The
      purpose of the present study was to report predictors for fusion and also to
      investigate the importance of radiological variables for the clinical outcome.
      Gender, age, smoking habits, disc height, segmental kyphosis and type of surgical
      procedure were used as independent (before surgery) variables in a multiple
      regression model. Male gender, one-level surgery and CP treatment were
      significant predictors of fusion and explained 14% of the variability of fusion
      status at follow-up. Number of levels operated on, however, did not influence the
      clinical outcome. Fifty-two per cent of the women and 17% of the men in the CIFC
      group, and 25% of the women and 8% of the men in the CP group, had
      pseudarthrosis. Although patients with a healed fusion had significantly less
      pain intensity than patients with pseudarthrosis, radiological variables
      explained only 4% of the variability of pain at follow-up. Apart from a
      significant correlation between preoperative kyphosis and neck disability index
      at follow-up, no significant correlation between either postoperative kyphosis or
      preoperative or postoperative disc height and clinical outcome was found. Neither
      degree of segmental kyphosis nor disc height was different between patients with
      healed fusion and pseudarthrosis. One can conclude that male gender and type of
      surgery were significant predictors for a healed fusion and that pseudarthrosis
      affected outcome. In contrast to the commonly held view based mainly on
      theoretical considerations, no effect on clinical outcome could be demonstrated
      for segmental kyphosis and disc height at follow-up. Overall, the study shows
      that the importance of radiological factors as predictors for fusion as well as
      clinical outcome is limited.

PMID- 14714243
TI  - Outcomes of a prospective cohort study on peri-radicular infiltration for
      radicular pain in patients with lumbar disc herniation and spinal stenosis.
AB  - The purpose of this study was to assess the outcome of peri-radicular
      infiltration for radicular pain in patients with spinal stenosis and lumbar disc
      herniation (LDH). Patients with spinal stenosis ( n=62) or LDH ( n=55) who met
      our criteria received fluoroscopically guided peri-radicular infiltration of
      local anaesthetic and steroid at the site of documented pathology. All the
      patients were followed-up at 3 months. There was a statistically significant
      difference in the functional outcome between the spinal stenosis group and the
      LDH group. The mean change in the Oswestry disability index (ODI) score for the
      spinal stenosis group was 5.5% compared to 12% for the LDH group. The spinal
      stenosis group had a mean change in visual analogue scales (VAS) of 1.2 compared
      to 2 for the LDH group. The higher the modified somatic perception score,
      modified zung depression and age at injection, the less favourable the outcome.
      There was a significantly better response to peri-radicular infiltration for
      radicular pain in patients with LDH than the spinal stenosis. Our findings help
      us to provide a better information for future patients. We do not know if this is
      a treatment effect or natural history of the pathology, as this is a cohort study
      and not a randomised controlled trial.

PMID- 14714244
TI  - Platelet calmodulin levels in adolescent idiopathic scoliosis (AIS): can they
      predict curve progression and severity? Summary of an electronic focus group
      debate of the IBSE.
AB  - There is no generally accepted scientific theory for the etiology of idiopathic
      scoliosis. As part of its mission to widen understanding of scoliosis etiology,
      the International Federated Body on Scoliosis Etiology (IBSE) introduced the
      electronic focus group (EFG) as a means of increasing debate of extant knowledge
      on important topics. This has been designated as an on-line Delphi discussion.
      The text for this EFG was written by Professor Thomas G Lowe MD and drawn from
      research carried out by himself and his co-workers on platelet calmodulin levels
      in patients with adolescent idiopathic scoliosis. To explain the relationship of
      platelet calmodulin levels to scoliosis curve changes in AIS brought about
      spontaneously, by brace treatment, or surgery Dr Lowe attributes the platelet
      calmodulin changes to paraspinous muscle activity and suggests that the
      calmodulin acts as a systemic mediator of tissues having a contractile system
      (actin and myosin). Controversy includes: 1) the lack of normal data and the
      large variability in baseline levels of platelet calmodulin, necessitating the
      use of the AIS subjects as their own controls; 2) calmodulin is not usually used
      as a marker of platelet activation; 3) whether the platelet calmodulin changes
      which appear to reflect an abnormality of a portion of the spine are related to
      local and/or regional changes in muscles, nervous system, or immature vertebrae.
      What is not controversial is the need for more research on platelets and the
      immature deforming skeleton in relation to etiology and prognosis.

PMID- 14714245
TI  - Kyphectomy in myelomeningocele with a modified Dunn-McCarthy technique followed
      by an anterior inlayed strut graft.
AB  - Rigid congenital kyphosis in myelomeningocele is associated with an important
      morbidity with skin breakdown, recurrent infection, and decreased function.
      Kyphectomy is the classic treatment to restore spinal alignment; however, surgery
      is associated with an important morbidity and long-term correction is uncertain.
      The authors retrospectively reviewed 9 patients with a mean age of 8.8 years who
      underwent a two stage surgical procedure: first a posterior kyphectomy with a
      modified Dunn-McCarthy fixation consisting of lumbar pedicle screws and long S
      shape rods buttressing the anterior sacrum. Then a second stage done several
      weeks later consisting of a thoraco-abdominal approach to the spine with an inlay
      strut graft classically from T10-S1. The mean follow-up was 34 months (range 1-5
      years). The kyphosis was corrected from a mean of 110 degrees of Cobb angle
      (range 70-130 degrees) to 15 degrees after surgery (45-0 degrees). There was no
      instrumentation failure, no loss of correction and no pseudarthrosis.
      Complications consisted of one intra-operative cardiac arrest fortunately
      reversible, a wound necrosis, one deep venous thrombosis and one late aseptic
      bursitis on the posterior hardware. Congenital kyphosis in myelomeningocele can
      be treated successfully with an initial posterior approach correction and
      instrumentation followed by an anterior approach allowing for anterior inlay
      impacted structural graft. The authors believe that this technique improves
      biomechanical and biological fusion mass anteriorly and will prevent late
      instrumentation failure and loss of correction.

PMID- 14714247
TI  - Efficacy of surveillance and molecular markers for detection of ulcerative
      colitis-associated colorectal neoplasia.

PMID- 14714246
TI  - Longitudinal validation of the fear-avoidance beliefs questionnaire (FABQ) in a
      Swiss-German sample of low back pain patients.
AB  - Work and activity-specific fear-avoidance beliefs have been identified as
      important predictor variables in relation to the development of, and treatment
      outcome for, chronic low back pain. The objective of this study was to provide a
      cross-cultural German adaptation of the Fear-Avoidance Beliefs Questionnaire
      (FABQ) and to investigate its psychometric properties (reliability, validity) and
      predictive power in a sample of Swiss-German low back pain patients.
      Questionnaires from 388 operatively and non-operatively treated patients were
      administered before and 6 months after treatment to assess: socio-demographic
      data, disability (Roland and Morris), pain severity, fear-avoidance beliefs,
      depression (ZUNG) and heightened somatic awareness (MSPQ). Complete baseline and
      follow-up questionnaires were available from 255 participants. The corrected item
      total correlations, coefficients of test-retest reliability and internal
      consistencies of the two scales of the questionnaire were highly satisfactory. In
      a confirmatory factor analysis (CFA), all items loaded on the appropriate factor
      with minor loadings on the other. Cross-sectional regression analysis with
      disability and work loss as the dependent variables yielded results that were
      highly comparable with those reported for the original version. Prognostic
      regression analysis replicated the findings for work loss. The cross-cultural
      German adaptation of the FABQ was very successful and yielded psychometric
      properties and predictive power of the scales similar to the original version.
      The inclusion of fear-avoidance beliefs as predictor variables in studies of low
      back pain is highly recommended, as they appear to have unique predictive power
      in analyses of disability and work loss.

PMID- 14714248
TI  - Helicobacter pylori and TT virus prevalence in Japanese children.
AB  - BACKGROUND: The major transmission route of Helicobacter pylori, oral-oral or
      fecal-oral, remains to be established. TT virus (TTV), a recently discovered
      microbe that is prevalent in healthy persons, is believed to be mainly
      transmitted by nonparenteral routes. The purpose of this study was to test the
      hypothesis that these two microorganisms have a common mode of transmission.
      METHODS: We investigated the seroprevalence of H. pylori and TTV in a cross
      sectional study of 454 healthy Japanese children from birth to age 15 years,
      living in five different geographic areas. Determination of H. pylori status was
      based on the presence of specific serum IgG and IgA antibodies, determined using
      enzyme immunoassays. TTV DNA was detected and the titer was determined using
      semiquantitative polymerase chain reaction with heminested primers. RESULTS: The
      overall prevalences of H. pylori and TTV were 12.2% and 21.6%, respectively. An
      age-related increase of prevalence was shown for H. pylori ( P < 0.001), but not
      for TTV ( P = 0.23). Titers of TTV DNA significantly decreased with age (P =
      0.02). There were significant geographic differences in TTV prevalence ( P <
      0.001), but not in H. pylori seroprevalence (P = 0.33). There was no true
      correlation between the prevalence of these two organisms (Phi coefficient = 
      0.02 and P = 0.66). CONCLUSIONS: Although Japanese children frequently acquire
      both H. pylori and TTV, especially in early childhood, their acquisition appears
      to be independent.

PMID- 14714249
TI  - Interaction of Helicobacter pylori-induced follicular gastritis and autoimmune
      gastritis in BALB/c mice with post-thymectomy autoimmune gastritis.
AB  - BACKGROUND: There is still controversy about the relationship between
      Helicobacter pylori infection and autoimmune gastritis. The aim of this study was
      to clarify whether or not H. pylori infection interacts with the development of
      autoimmune gastritis. METHODS: Neonatally thymectomized BALB/c mice with
      autoimmune gastritis received orally administered H. pylori and were examined
      histologically and serologically. The T-helper (Th)1/Th2 immune balance in the
      microenvironment of the stomach was evaluated by reverse-transcriptase-polymerase
      chain reaction (RT-PCR) for interferon (IFN)-gamma and interleukin (IL)-4.
      RESULTS: Uninfected mice showed disappearance of parietal cells, and upregulation
      of IFN-Gamma, but no germinal center formation. The infected neonatally
      thymectomized mice showed follicular gastritis, preserved parietal cells,
      decreased serum anti-parietal antibodies, and upregulation of IL-4 and IFN-gamma.
      CONCLUSIONS: H. pylori infection changes the microenvironment of the gastric
      mucosa by inducing a Th2 immune response in addition to a Th1 response, and
      regresses autoimmune gastritis in neonatally thymectomized BALB/c mice.

PMID- 14714250
TI  - Reliability, validity, and responsiveness of the Japanese version of the
      Inflammatory Bowel Disease Questionnaire.
AB  - BACKGROUND: Inflammatory bowel disease affects the quality of a patient's life in
      many ways, but no validated instrument for measuring disease-specific quality of
      life in these patients is available in Japan. We developed a Japanese version of
      the Inflammatory Bowel Disease Questionnaire (IBDQ), together with the author of
      the original English-language version. METHODS: Translation and cross-cultural
      adaptation followed an accepted process. The reliability, validity, and
      responsiveness of the IBDQ's four subscales were then assessed in a prospective
      cohort of Crohn's disease patients who underwent hospitalization. RESULTS:
      Internal consistency was acceptable for all four subscales. Concurrent validity
      (with the Short Form [SF]36 as a reference) was as expected. Scores on the IBDQ
      could be used to discriminate patient subgroups with different levels of disease
      activity. Responsiveness was comparable to that of the SF36. CONCLUSIONS: This
      Japanese version of the IBDQ is reliable, valid, and responsive for assessing
      disease-specific quality of life in patients with Crohn's disease.

PMID- 14714251
TI  - High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and
      intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its
      potential use in the diagnosis of liver neoplasms.
AB  - BACKGROUND: An increased level of high mobility group A (HMGA) gene/protein
      expression has been demonstrated to be associated with many human neoplasms
      originating from a variety of tissues. However, HMGA1 expression has not yet been
      studied in hepatic tumors. In this study, we analyzed HMGA1 expression in hepatic
      primary and metastatic tumors in order to verify whether determination of the
      HMGA1 expression level could provide any diagnostic advantages in the
      pathological diagnosis of hepatic tumors. METHODS: Twenty samples of
      hepatocellular carcinoma, 5 samples of intrahepatic cholangiocarcinoma, and 21
      samples of metastatic adenocarcinoma to the liver (15 metastatic tumors from
      colorectal carcinoma and 6 metastatic tumors from pancreatic carcinoma) were
      analyzed immunohistochemically using an HMGA1-specific antibody. RESULTS: While
      no significant nuclear immunoreactivity was found in hepatocytes of non
      neoplastic liver tissue, 40% (2/5) of intrahepatic cholangiocarcinomas, 53.3%
      (8/15) of metastatic lesions from colorectal carcinoma, and 100% (6/6) of
      metastatic lesions from pancreatic carcinoma showed positive immunoreactivity. In
      contrast, all 20 samples of hepatocellular carcinoma were negative for HMGA1
      nuclear immunoreactivity. Thus, hepatocellular carcinoma represents the first
      case of malignant neoplasia in which HMGA1 expression is not induced, which
      presents a striking contrast to several previous studies demonstrating the
      significance of increased HMGA gene/protein levels in carcinogenesis and/or tumor
      progression. CONCLUSIONS: Based on these findings, we conclude that the HMGA1
      protein level could serve as a potential diagnostic marker that may enable the
      differential diagnosis between hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma or metastatic adenocarcinoma to the liver.

PMID- 14714252
TI  - Captopril reduces portal pressure effectively in portal hypertensive patients
      with low portal venous velocity.
AB  - BACKGROUND: The effect of an angiotensin II blockade in lowering the portal
      pressure in patients with liver cirrhosis and portal hypertension is
      controversial. This prospective study was undertaken to evaluate the portal
      hypotensive effect of captopril compared to that of propranolol, and to determine
      the factors that contribute to a successful reduction in the portal pressure
      after longterm captopril administration in patients with liver cirrhosis.
      METHODS: The hepatic venous pressure gradient (HVPG) and portal venous velocity
      (PVV) were measured both before and 3 months after initiation of the
      administration of captopril (n = 29) or propranolol (n = 29) in cirrhotic
      patients with a variceal bleeding episode. Patients who showed a reduction in the
      HVPG of more than 20% of the baseline were defined as being responders. RESULTS:
      At 3 months, the mean reduction in the HVPG after captopril was less than that
      after propranolol (-3.0 +/- 9.3% vs -28.5% +/- 4.1%; P < 0.05). However, of the
      29 patients receiving captopril, 9 were classified as being responders. On
      multivariate analysis with parameters including age, cause, Child-Pugh score,
      HVPG, and PVV, only low PVV was found to be a significant independent factor for
      responders (PVV < 12 cm/s; odds ratio [OR], 12.2; 95% confidence interval [CI],
      1.47-102.40) in the captopril group. CONCLUSIONS: Longterm captopril
      administration reduces the portal pressure effectively in cirrhotic patients with
      a low PVV. This suggests that the reduction in portal pressure after captopril
      administration is a result of improved portal venous outflow brought about by a
      decrease in the intrahepatic vascular resistance. When the PVV is below 12 cm/s,
      a captopril trial might be useful in preventing variceal bleeding in portal
      hypertensive patients.

PMID- 14714253
TI  - Ultrasonographic evaluation in patients with autoimmune-related pancreatitis.
AB  - BACKGROUND: The concept of autoimmune-related pancreatitis (AIP) has recently
      been described. It is important to exclude pancreaticobiliary malignancy in
      patients with AIP who develop distal bile duct strictures. The aim of this study
      was to evaluate distal common bile duct strictures in AIP patients by endoscopic
      ultrasonography (EUS), intraductal ultrasonography (IDUS), and contrast-enhanced
      EUS (ceEUS). METHODS: Five patients with AIP, encountered from January 2000
      through December 2001, underwent EUS, IDUS, and ceEUS, using Levovist as a
      contrast medium. EUS and ceEUS were used to follow changes in distal bile duct
      strictures in three of these five patients following a trial of steroid therapy.
      RESULTS: Of the five patients, four had cholestatic biochemical profiles, three
      were positive for autoantibodies, and three had elevated serum immunoglobulin G
      (IgG) or IgG4. A diffusely enlarged pancreas, narrowing of the main pancreatic
      duct (MPD), and strictured common bile duct in the pancreatic head were features
      common to all patients. Pretherapy EUS or IDUS imaging showed concentric wall
      thickening of the distal common bile duct causing bile duct stenosis. ceEUS
      showed diffuse strong enhancement of the thickened bile duct wall, possibly due
      to inflammation. After the steroid therapy, the stenotic lesions in both the MPD
      and distal common bile duct were rapidly attenuated, with a decline in
      biochemical cholestatic enzymes and serum IgG or IgG4 levels. CONCLUSIONS: On EUS
      and IDUS imaging, concentric bile duct wall thickening and its strong enhancement
      by Levovist was characteristic in AIP patients.

PMID- 14714254
TI  - Increased expression of MUC1 in advanced pancreatic cancer.
AB  - BACKGROUND: MUC1 is associated with tumor invasion and metastasis, and is
      expressed in pancreatic cancer with a high frequency. This study explored whether
      MUC1 expression affected the survival of patients with pancreatic cancer.
      METHODS: Tissue specimens obtained from 70 patients with invasive ductal
      carcinoma of the pancreas, in pTNM stage III or IV, were immunostained with the
      anti-MUC1 monoclonal antibody DF3. The results of immunostaining were determined
      to be positive when more than 50% of the total cancer cells were positively
      stained. Association of the expression of the DF3 epitope with
      clinicopathological parameters or patients' survival was statistically evaluated.
      RESULTS: The incidence of positivity of MUC1 expression was 55.7% (39/70) and
      this incidence was significantly higher in pTNM stage IV than in stage III (odds
      ratio [OR], 4.015; 95% confidence interval [CI], 1.459-11.0541; P = 0.0076). As
      there was a clear difference in overall survival between pTNM stages III and IV (
      P = 0.0016), the effect of MUC1 expression on survival was separately evaluated
      in each stage. It was shown that the expression of MUC1 was associated with
      unfavorable overall survival in stage IV ( P = 0.0197). CONCLUSIONS: Our data
      suggest that the expression of MUC1 may be related to the progression of
      pancreatic cancer.

PMID- 14714255
TI  - Tuberculous peritonitis.
AB  - We report a case of tuberculous peritonitis in a 24-year-old male patient. On
      admission, he was complaining of abdominal fullness and fever. Ultrasound
      tomography and computed tomography (CT) scan of the abdomen showed massive
      ascites with multiple septa. The most interesting feature of this case was the
      diffuse and intense uptake of gallium-67 in the abdomen. Though the initial chest
      X-ray showed only slight bilateral pleural effusion, and cultures from ascites,
      stool, sputum, and pleural effusion were negative for Mycobacterium tuberculosis,
      CT scan of the lung showed a small consolidation shadow with contractile change,
      similar to tuberculosis. A few days after the CT scan of the lung, the sputum was
      positive for Mycobacterium tuberculosis. Finally we diagnosed active tuberculous
      peritonitis, and then started antituberculous therapy. In patients with massive
      ascites and fever of unknown origin, tuberculous peritonitis must be considered.
      Gallium-67 scintigraphy has been shown to be useful when there is a high index of
      suspicion of tuberculous peritonitis.

PMID- 14714256
TI  - Adenosquamous carcinoma of the pancreas: preoperative diagnosis and molecular
      alterations.
AB  - Adenosquamous carcinoma of the pancreas is a rare tumor which has a less
      favorable prognosis than common ductal cell carcinoma of the pancreas, and a
      definite preoperative diagnosis of this tumor is quite difficult. We herein
      report two cases of this rare variant. The patients were a 41-year-old man
      (patient 1) and a 67-year-old woman (patient 2). Patient 1 had a hypoechoic mass
      measuring 3 cm in the uncus of the pancreas, while patient 2 had a huge mass,
      measuring 8 cm, in the tail of the pancreas. Patient 2 was successfully diagnosed
      preoperatively as having an adenosquamous carcinoma, by cytological examination
      of the pure pancreatic juice obtained by endoscopic retrograde pancreatic juice
      aspiration. A pylorus-preserving pancreatoduodenectomy was performed for patient
      1, and a distal pancreatectomy with resection of the spleen and the left kidney
      was performed for patient 2. Subsequent pathological findings of these two tumors
      revealed adenosquamous carcinoma of the pancreas. K- ras point mutation, p53
      overexpression, and telomerase activity in both tumor specimens were detected by
      the mutant allele specific amplification method, immunohistochemical staining,
      and telomeric repeat amplification protocol assay, respectively. The two patients
      died of recurrent disease 5 and 4 months, respectively, after surgery.
      Cytological examination of pure pancreatic juice is a useful modality for the
      preoperative diagnosis of this tumor, and frequent molecular alterations may be
      associated with the poor prognosis of adenosquamous carcinoma of the pancreas.

PMID- 14714257
TI  - Early gastric cancer with Krukenberg tumor and review of cases of intramucosal
      gastric cancers with Krukenberg tumor.
AB  - A 47-year-old woman was admitted because of hypermenorrhea. Transvaginal
      ultrasonography revealed an ovarian tumor and myoma uteri, and total hysterectomy
      with bilateral salpingo-oophorectomy was performed. Histology revealed signet
      ring cell carcinoma in the right ovary. In order to find out the primary site of
      this tumor, gastroendoscopy was performed after the operation, and showed a IIc
      lesion in the lower body of the stomach; biopsy specimens showed signet-ring cell
      carcinoma similar to that in the right ovary. Total gastrectomy revealed that the
      lesion was an early gastric cancer confined to the mucosa, but there was
      lymphatic invasion slightly beneath the muscularis mucosa, with regional lymph
      node metastasis. In the light of a review of the seven cases of early gastric
      cancer with Krukenberg tumor previously reported, lymphatic metastasis seemed to
      be the most likely pathway of ovarian metastasis in early gastric cancers.

PMID- 14714259
TI  - Genetic analysis of radiation-associated rectal cancer.
AB  - Genetic aberrations in radiation-associated colorectal cancer have not been
      studied in detail. We analyzed genetic aberrations in five rectal cancers that
      developed long after radiotherapy had been performed for cervical cancer.
      Microsatellite instability (MSI) in tumors was examined at five loci: D2S123,
      D3S966, TP53, DCC, and BAT26. Mutation of simple repeat sequences within the
      hMSH3, BAX, and transforming growth factor Beta type II receptor ( TGFBetaRII)
      genes was examined by polymerase chain reaction and single-strand conformation
      polymorphism (PCR-SSCP). Mutation of p53 exons 5-8 was examined by PCR-SSP and
      direct sequencing. Mutations of the K- ras gene were analyzed by two-step PCR. No
      MSI was found in tumor specimens at any of the loci examined, and no mutations in
      the target genes were observed. K- ras mutation was detected in two carcinomas,
      but not in their irradiated normal mucosa, while p53 mutation was observed in
      another two carcinomas, but not in their irradiated normal mucosa. Our results
      suggest that the radiation-associated rectal carcinomas examined in this study
      did not develop through the mutator phenotype pathway; rather, tumorigenesis was
      probably mediated through the multistep carcinogenesis pathway.

PMID- 14714258
TI  - Exophytic pedunculated gastrointestinal stromal tumor with remarkable cystic
      change.
AB  - A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon
      carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US)
      showed another tumor, with an uneven irregular surface, measuring about 9 x 5 cm,
      below the left hypochondrium. The tumor consisted of several cysts. Abdominal
      computed tomography (CT) showed a multicystic tumor attached to the stomach, and
      its septum and marginal region were intensely stained on contrast imaging. On
      magnetic resonance imaging (MRI), low and markedly high signals were revealed in
      the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast
      imaging of the upper digestive tract showed extramural compression of the greater
      curvature of the antral stomach by the tumor. The tumor was partially imaged by
      endoscopic ultrasonography (EUS), but continuity to the stomach was not
      confirmed. On abdominal angiography, the tumor was slightly stained via the
      gastroepiploic arteries. Surgical treatment was performed to excise both the
      gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with
      gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was
      multicystic, contained watery fluid, and had a smooth outer surface.
      Histologically, the tumor consisted of multiple irregular cysts without
      epithelial lining, and solid epitheloid cell nests in between. The tumor cells
      had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were
      seen. The tumor cells in the pedicle were connected with the muscularis propriae
      of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth
      muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The
      final diagnosis was gastrointestinal stromal tumor (GIST).

PMID- 14714260
TI  - Positron emission tomography with 2-deoxy-2-[(18)F] fluoro- d-glucose for
      diagnosis of intraductal papillary mucinous tumor of the pancreas with
      parenchymal invasion.
AB  - We used positron emission tomography with 2-deoxy-2-[(18)F]fluoro- d-glucose (FDG
      PET) in the diagnosis of two cases of malignant intraductal papillary mucinous
      tumor (IPMT) of the pancreas. A 56-year-old man and a 72-year-old man, both with
      tumors in the pancreatic head, were referred to Akita University Medical Center.
      Computed tomography revealed tumors with multiple cystic components in both
      patients. FDG-PET images showed markedly high FDG uptake in the area
      corresponding to a solid component found in one patient and diffuse faint uptake,
      higher than that of the surrounding tissue, in the other patient, who had no
      solid component. Histological examination of the resected specimens after
      pancreatectomy showed invasive carcinoma involving the pancreatic parenchyma in
      both patients. Although our experience is limited and preliminary, FDG-PET seems
      to be useful for the detection of malignancy in IPMT, especially in patients not
      showing any solid component on conventional diagnostic images such as computed
      tomography.

PMID- 14714261
TI  - Multiple synchronous early gastric carcinoma with seven lesions.

PMID- 14714262
TI  - A case of ischemic colitis during pregnancy.

PMID- 14714263
TI  - Hepatosplenic abscess due to candida infection effectively treated by the
      intraarterial injection of an antimycotic agent using an implanted reservoir.

PMID- 14714264
TI  - The suppressive effect of Helicobacter pylori infection against the development
      of autoimmune gastritis: analysis in neonatally thymectomized BALB/c mice.

PMID- 14714265
TI  - Autoimmune pancreatitis and bile duct lesions.

PMID- 14714266
TI  - The effect of levothyroxine therapy on bone mineral density: a systematic review
      of the literature.
AB  - BACKGROUND: Currently debate still exists about the effects of thyroid hormone
      therapy on skeletal integrity, that is the safety of levothyroxine use with
      respect to bone mineral density. OBJECTIVE: A systematic review of the effects of
      TSH-suppressive and replacement levothyroxine therapy on bone mineral density
      evaluated main causes of conflicting results and its implications for clinical
      practice, and suggested directions of future research. DATA SOURCE AND STUDY
      SELECTION: A MEDLINE search identified English-language studies assessing bone
      mineral density under levothyroxine therapy published from 1990 to 2001. DATA
      EXTRACTION: The studies were grouped by design and type of intervention. Outcomes
      were qualitatively analysed. Subgroup analysis assessed heterogeneity between
      studies. DATA SYNTHESIS: Of 63 identified studies, 31 studies reported no effects
      of levothyroxine on bone mineral density, 23 studies showed partial beneficial or
      adverse, and 9 studies overall adverse effects. A significant dose-response was
      not found. There was a tendency towards peripheral cortical bone loss, suggesting
      a site-specific effect. In adolescents, men, and premenopausal women evidence for
      levothyroxine influence was weaker than in postmenopausal women. However, also
      findings in postmenopausal women remained unclear. The extent and etiology of
      underlying thyroid diseases also contributed to inconsistent results. Further,
      controversial results were due to substantial heterogeneity of studies. Above
      all, studies were limited by moderate quality, small size, and inadequate control
      for confounders. CONCLUSIONS: Based on current studies there is insufficient
      evidence about effectiveness of levothyroxine on bone mineral density. All
      conclusions, however, must take into account the important methodical drawbacks.
      Present data may only be proved by longitudinal, high quality studies in
      homogeneous patients with sufficient sample size, clinical implication of future
      research remains questionable, though.

PMID- 14714267
TI  - Minimal metabolic data set for patients at high vascular risk.
AB  - Vascular events still represent the leading cause of death in the western world.
      The pathogenesis of atherothrombotic events is multifactorial. Epidemiological
      studies indicate that the presence of several concomitant risk factors,
      especially in the metabolic syndrome, markedly exacerbates the vascular risk. In
      the prevention and management of cardiovascular disease, a multi-dimensional risk
      factor approach is therefore required to reduce the "vascular burden".
      Consequently it is absolutely necessary to identify and to subsequently monitor
      these factors during intervention/therapy. The present MMDS represents a tool for
      the daily clinical routine to assess and document important cardiovascular risk
      factors. This data set is the result of a consensus of the two German working
      groups of the German Cardiology Society and the German Diabetes Society. The
      identification and detection of all relevant vascular risk factors should result
      in improved patient care and a more comprehensive documentation of cardiovascular
      risk factors in clinical studies.

PMID- 14714268
TI  - Molecular cloning of porcine neuronatin and analysis of its expression during
      pituitary ontogeny.
AB  - We cloned and sequenced two types (alpha and beta type) of cDNA from the porcine
      anterior pituitary cDNA library, encoding neuronatin that has been cloned as a
      gene expressed by the fetal developing brain. Nucleotide sequences of alpha and
      beta type were identical except for two gaps, suggesting that they were produced
      by an alternative splicing. The amino acid sequences showed a high homology (more
      than 94 %) compared to those of other mammals, including human, rat, and mouse.
      In this study, RT-PCR was performed for the RNA samples prepared from the porcine
      fetal and postnatal pituitaries. The results showed that two types of neuronatin
      are expressed through the fetal stages, from day 40 to day 110 in both sexes. The
      relative amounts of alpha to beta type reversed just after birth in both sexes,
      and both amounts increased further in the postnatal anterior pituitary. This
      increased expression after birth is quite different from the brain in which the
      expression of neuronatins decreased, indicating the distinct role of the
      neuronatin in pituitary and brain. Finally, we found a pituitary cell type
      specific localization, especially in gonadotroph cell lines LbetaT2, of beta
      neuronatins.

PMID- 14714269
TI  - Prevalence of thyroid dysfunction in adults over age 60 years from an urban
      community.
AB  - Thyroid dysfunction affects a considerable portion of the elder population. The
      aim of the present study has been to assess the prevalence of thyroid dysfunction
      in adult healthy subjects over age 60 years from our population. We performed a
      descriptive, cross-sectional study in the setting of a sanitary area in an urban
      community in Madrid (Spain). Serum concentrations of thyrotropin (TSH) and free
      thyroxine (FT4) were determined by an electrochemiluminescency assay in all
      participants after antecubital venous sampling. A second examination, including
      the measurement of triiodothyronine and thyroid autoantibodies, was performed in
      subjects with abnormal results. A total of 127 women and 167 men, aged 60 to 84
      years, were studied. We identified 6 subjects (all women) with hypothyroidism
      (2.04 %) and 19 (6 women, 13 men) with hyperthyroidism (6.46 %, 95 %CI 3.65 -
      9.27 %). There were 3 cases (1.02 %) of subclinical and 3 cases (1.02 %) of overt
      hypothyroidism. In the hyperthyroid group only one patient (0.34 %) showed overt
      hyperthyroidism. TSH test did not detect erroneously any case of hypothyroidism
      or hyperthyroidism, although one patient with hyperthyroidism was not diagnosed
      by this test. FT4 test detected erroneously two cases of hypothyroidism; however,
      it was the only way to detect the patient with overt hyperthyroidism. In
      conclusion, in our population over age 60 years the prevalence of hypothyroidism
      was 2.04 % and that of hyperthyroidism 6.46 % (95 %CI 3.65 - 9.27 %). The total
      prevalence of thyroid dysfunction was, therefore, 8.50 % (95 %CI 5.31 - 11.69).
      Our data suggest that TSH test is probably enough to screen for thyroid
      dysfunction in adults over age 60 years.

PMID- 14714270
TI  - Calcium metabolism and endocrine functions in a family with familial
      hypocalciuric hypercalcemia.
AB  - OBJECTIVE: We report two Hungarian patients with familial hypocalciuric
      hypercalcemia (FHH) caused by a mutation of the calcium-sensing receptor (CaSR)
      at codon 55. The proband and her father were heterozygous for this mutation.
      DESIGN: We performed detailed clinical and laboratory assessments of this family
      to characterize the effects of CaSR mutation on several endocrine organs
      expressing CaSR. RESULTS: Interestingly, we could not detect any failure in the
      function of any tissues we examined, except in serum calcium levels. CONCLUSIONS:
      To our knowledge, this has been the first report from Eastern and Central Europe
      showing P55 L mutation of the CaSR, as well as the first publication discussing
      the effect of this mutation on several endocrine systems containing CASR.

PMID- 14714271
TI  - Therapeutic dose of HIV-1 protease inhibitor saquinavir does not permanently
      influence early insulin signaling.
AB  - The introduction of HIV-1 protease inhibitor therapy has significantly improved
      the expectancy and quality of life for HIV-infected patients. Recent reports have
      highlighted the development of metabolic complications in patients taking
      protease inhibitors, including abnormalities in glucose metabolism such as
      impaired glucose tolerance and type 2 diabetes. The mechanisms by which protease
      inhibitors induce these metabolic syndromes are not well understood. The aim of
      this study was to determine whether treatment with the HIV-1 protease inhibitor,
      saquinavir, influences the early insulin signaling cascade in insulin-sensitive
      cell lines. METHODS: Insulin-stimulated phosphorylation of insulin receptor (IR
      beta), insulin receptor substrates (IRS-1 and IRS-2), association of
      phosphatidylinositol 3-kinase (PI 3-kinase), Ser 473-phosphorylation of Akt and
      Thr202/Tyr204-phosphorylated p44/42 MAP kinase in 3T3L1 adipocytes and FAO
      hepatoma cells incubated with increasing concentrations of saquinavir for 24, 36
      hours, 2, 3 and 6 days were measured. Results. Phosphorylation of IR-beta, IRS-1
      and IRS-2 was not permanently affected by incubation with therapeutic doses (2.5
      microM) of saquinavir for 36 hours. After 24 hours we observed an increase of IR
      beta and IRS-1 phosphorylation. However, this initial stimulation of IR-beta and
      IRS-1 phosphorylation was not permanent and did not result in an increased PI 3
      kinase association. Phosphorylation of IRS-2 and MAP kinase as well as glucose
      transport activity was not altered by therapeutic doses. Doses of 10, 25 and 50
      microM of saquinavir altered the early insulin signaling events in a dose
      dependent manner. However, this effect was primarily due to the cytotoxic effect
      of higher saquinavir doses. Glucose transport activity was not significantly
      reduced in 3T3L1 cells treated with 2.5 microM saquinavir in comparison to the
      control cells stimulated with insulin. CONCLUSION: Early insulin signaling
      cascade, essential for normal glucose metabolism, is not affected by therapeutic
      doses of saquinavir. The reduction of insulin-induced phosphorylation in higher
      concentrations is primarily related to cytotoxic effects. Other mechanisms than
      early insulin signaling must be primarily responsible for the metabolic
      alterations during saquinavir therapy.

PMID- 14714272
TI  - Effect of alpha-ketobutyrate on microvascular thickness in the diabetic rat
      kidney.
AB  - The first objective of this study was to examine the intermediary metabolism of
      plasma amino acids and keto acids in streptozotocin (STZ)-treated rats. Plasma
      alpha-aminobutyrate (alpha-ABA) concentration in STZ rats was 1.5-fold greater
      than in control (CNT) animals at 1 month. In contrast, the level of plasma alpha
      ketobutyrate (KB), which is transaminated to alpha-ABA, did not differ
      significantly between STZ and CNTs at 1 month, and also increased with age.
      Additionally, HPLC analysis revealed consistent profiles containing peaks of
      unknown origin. Two pathways exist for the formation of alpha-KB, either from the
      action of threonine dehydratase or via homocysteine, the latter metabolite being
      closely associated with the development of cardiovascular disease. These
      observations suggest that uncharacterized metabolites, including plasma alpha-KB,
      may be potential risk factors for the development of diabetic complications. We
      carried out preparatory experiments on non-diabetic rats to investigate the
      influence of alpha-KB and confirmed this metabolite had no adverse effects. The
      second aim of the study was to compare vascular wall thickness in diabetic rats
      treated or untreated with alpha-KB with CNT animals in order to determine the
      effects of alpha-KB on the renal microvasculature. The thickness of the medial
      wall of arterioles and small arteries differed significantly among all groups and
      was increased, especially in the small arterial walls of the diabetic rats
      treated with alpha-KB. Plasma renin activities (PRA) in both diabetic rats
      treated or untreated with alpha-KB were decreased significantly compared to CNT
      animals, while diabetic rats treated with alpha-KB had higher angiotensin
      converting enzyme (ACE) activity than the CNT group (p < 0.01). These results
      suggest that alpha-KB may have a role in the renal microvascular complications of
      diabetes.

PMID- 14714273
TI  - Vitamin D receptor gene polymorphisms and association with type 2 diabetes
      mellitus in a Polish population.
AB  - Vitamin D plays an important role in insulin secretion. There is also evidence
      that this steroid may influence the insulin sensitivity. Thus genes involved in
      its metabolic pathway have been regarded as good candidates for type 2 diabetes
      mellitus (T2DM). One of them is vitamin D receptor gene (VDR). Its multiple
      polymorphisms have been examined for the association with T2DM in several
      populations. Those studies did not provide clear answers about the role of VDR in
      this disease. The aim of the study was to search for the association of FokI,
      ApaI, BsmI, and TaqI polymorphisms of VDR gene with T2DM in a Polish population
      using a case-control study design. Overall, 548 individuals were examined: 308
      T2DM patients and 240 control individuals. The study groups were genotyped for
      VDR FokI, ApaI, BsmI, and TaqI variants using the restriction fragment length
      polymorphism (RFLP) method. Since variants of ApaI, BsmI, and TaqI polymorphisms
      were in very strong linkage disequilibrium, three loci haplotypes could be
      assigned to phase-unknown individuals with a high degree of confidence.
      Differences in allele, genotype, haplotype, and haplotype combination
      distribution between the groups were examined by chi2 test. The VDR allele
      frequencies for T2DM patients and controls were as follows: FokI-F/f - 53.4
      %/46.6 % vs. 55.2 %/44.8 %, BsmI-B/b - 34.4 %/65.6 % vs. 37.5 %/62.5 %, ApaI-A/a 
      47.9 %/52.1 % vs 50.9 %/49.1 %, TaqI-T/t - 67.6 %/32.4 % vs. 62.7 %/37.3 %,
      respectively. There was no difference between the groups in allele frequency.
      Similarly, distribution of genotypes, three locus BsmI/ApaI/TaqI haplotypes and
      their combinations were similar in the groups. In conclusion, our study did not
      provide evidence for the association of four examined VDR polymorphisms with T2DM
      in a Polish population. We postulate that to fully determine whether the sequence
      differences in VDR gene are susceptibility variants for T2DM, additional studies
      in different populations are required in a large study group.

PMID- 14714275
TI  - Animal source foods to improve micronutrient nutrition and human function in
      developing countries. Proceedings of a conference. June 24-26, 2002. Washington,
      DC, USA.

PMID- 14714274
TI  - Pathogenic mutations associated with cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy differently affect Jagged1
      binding and Notch3 activity via the RBP/JK signaling Pathway.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited vascular dementia characterized by
      the degeneration of smooth-muscle cells in small cerebral arteries. CADASIL is
      caused by mutations in NOTCH3, one of the four mammalian homologs to the
      Drosophila melanogaster NOTCH gene. Disease-associated mutations are distributed
      throughout the 34 epidermal growth factor-like repeats (EGFRs) that compose the
      extracellular domain of the Notch3 receptor and result in a loss or a gain of a
      cysteine residue in one of these EGFRs. In human adults, Notch3 expression is
      highly restricted to vascular smooth-muscle cells. In patients with CADASIL,
      there is an abnormal accumulation of Notch3 in the vessel. Molecular pathways
      linking NOTCH3 mutations to degeneration of vascular smooth-muscle cells are as
      yet poorly understood. In this study, we investigated the effect of CADASIL
      mutations on Notch3 activity. We studied five naturally occurring mutations: R90C
      and C212S, located in the previously identified mutational hotspot EGFR2-5;
      C428S, shown in this study to be located in the ligand-binding domain EGFR10-11;
      and C542Y and R1006C, located in EGFR13 and EGFR26, respectively. All five mutant
      proteins were correctly processed. The C428S and C542Y mutant receptors exhibited
      a significant reduction in Jagged1-induced transcriptional activity of a RBP/JK
      responsive luciferase reporter, relative to wild-type Notch3. Impaired signaling
      activity of these two mutants arose through different mechanisms; the C428S
      mutant lost its Jagged1-binding ability, whereas C542Y retained it but exhibited
      an impaired presentation to the cell surface. In contrast, the R90C, C212S, and
      R1006C mutants retained the ability to bind Jagged1 and were associated with
      apparently normal levels of signaling activity. We conclude that mutations in
      Notch3 differently affect Jagged1 binding and Notch3 signaling via the RBP/JK
      pathway.

PMID- 14714276
TI  - Is there a pink slip in your genes? Genetic discrimination in employment and in
      health insurance. Proceedings of a symposium. Cleveland State University, USA.
      December 2001.

PMID- 14714277
TI  - Acute heart failure during spinal surgery in a boy with Duchenne muscular
      dystrophy.

PMID- 14714278
TI  - Effects of parathyroid hormone and alendronate alone or in combination in
      osteoporosis.

PMID- 14714279
TI  - Effects of parathyroid hormone and alendronate alone or in combination in
      osteoporosis.

PMID- 14714280
TI  - Effects of parathyroid hormone and alendronate alone or in combination in
      osteoporosis.

PMID- 14714281
TI  - D-dimer in venous thromboembolism.

PMID- 14714282
TI  - D-dimer in venous thromboembolism.

PMID- 14714283
TI  - D-dimer in venous thromboembolism.

PMID- 14714284
TI  - Delayed onset of malaria--implications for chemoprophylaxis.

PMID- 14714285
TI  - Supply and demand: the shifting expectations of forensic anthropology in the
      United Kingdom.

PMID- 14714286
TI  - Forensic anthropology--regulation in the United Kingdom.

PMID- 14714287
TI  - Anthropological facial 'reconstruction--recognizing the fallacies, 'unembracing'
      the errors, and realizing method limits.
AB  - Despite being practiced for over the last 200 years, facial approximation methods
      remain in their infancy as the soft tissue prediction methods employed have not
      been tested and justified. Scientific testing is the only way forward and much of
      it is needed. The lack of systematic scientific tests in the past has enabled
      many misleading notions to become established. Many of these notions appear to
      have arisen and been sustained as a result of practitioner biases--this is
      clearly evident even in the name commonly used to describe the method of building
      faces from skulls, for "facial reconstruction" implies everything the method is
      not, e.g., technical/scientific, exact, and credible. Although facial
      approximation methods are useful for forensic investigation (even if they do not
      generate identifications through true positive recognitions of the faces), the
      public should beware of the marketing and political ploys employed within the
      profession. These ploys give rise to some impressive, but unjustifiable claims-
      but do not just take my word for it; evaluate the evidence for yourself with
      disregard to the indoctrination waged by the facial "reconstruction" field in
      general, including that promoted by what I have had to say here. Use your own
      reason and intellect and see which conclusions you reach.

PMID- 14714288
TI  - The endangered child: the personal identification of children in forensic
      anthropology.

PMID- 14714289
TI  - Non-forensic remains: the use of forensic archaeology, anthropology and burial
      taphonomy.

PMID- 14714290
TI  - The challenge of identifying deceased individuals in Brazil: from dictatorship to
      DNA analysis.

PMID- 14714291
TI  - The development of human rights investigations since 1945.

PMID- 14714292
TI  - A multidisciplinary approach to the investigation of crimes against humanity, war
      crimes and genocide: the Inforce Foundation.

PMID- 14714293
TI  - A comparative study of gunshot residue originating from 9 mm Luger ammunition
      from various producers.
AB  - Following previous work on differentiation between gunshot residue according to
      the type of ammunition used, a specific investigation was undertaken of traces
      originating from 9 mm Luger ammunition using SEM-EDX. The aim of this study was
      to determine whether GSR originating from this type of ammunition is similar, or
      whether differentiation could be made between particular manufacturers of Luger
      ammunition. The results were collected in the form of counts of particles in each
      of seven key elemental classes being combinations of lead, antimony and barium.
      These were then adjusted to a factor known as frequency of occurrence which
      allows comparison of the distribution of particles within the classes between
      samples with differences in absolute particle counts. The relationships between
      the samples were examined using non-parametric statistical tests: R-Spearman and
      tau-Kendall rank correlation coefficients. It has been found that most of the
      studied samples of GSR were similar to each other despite their originating from
      various manufacturers.

PMID- 14714294
TI  - An improved protocol for the examination of rogue WWW sites.
AB  - Internet server managers have a range of techniques available to help them
      improve service performance and security. These techniques can become barriers to
      the investigation of illicit or illegal activity. This paper describes some of
      the legitimate techniques which can be used to improve server performance or
      security, and which present challenges for the investigator. Furthermore, it
      proposes a rigorous procedure which should be followed to ensure that any
      investigation of a web site or server has been complete and accurate, and that
      all possible useful information has been extracted and examined.

PMID- 14714295
TI  - Delivery and evaluation of forensic science.

PMID- 14714296
TI  - Expression of vascular endothelial growth factor in the progression of cervical
      neoplasia and its relation to angiogenesis and p53 status.
AB  - OBJECTIVE: To evaluate vascular endothelial growth factor (VEGF) expression in
      the successive steps of cervical neoplasia and to determine its correlation with
      angiogenesis and p53 status. STUDY DESIGN: Immunohistochemical staining with a
      VEGF monoclonal antibody was performed on a total of 161 cervical specimens
      representing 12 normal epithelium, 33 cervical intraepithelial neoplasia (CIN) 1,
      30 CIN 3 and 86 squamous cell carcinomas. Microvessels were immunohistochemically
      labeled with an antibody to CD34. Computerized image analysis was used to
      evaluate microvessel density (MVD). p53 Status was determined by
      immunohistochemistry and direct sequencing of exons 5-8 of the p53 gene. RESULTS:
      VEGF expression progressively increased along the continuum from normal
      epithelium to squamous cell carcinoma (P < .05). MVD increased significantly with
      cervical neoplasia progression, from normal epithelium, through CIN, to squamous
      cell carcinoma (P < .001). A strong correlation was observed between VEGF
      expression and MVD (P < .001). p53 Protein expression was not detected in the
      normal epithelium or in CIN 1, while 3 (10%) of 30 CIN 3 and 28 (33%) of 86
      squamous cell carcinomas were positive for p53. VEGF expression correlated
      statistically with p53 protein expression (P < .001). In double VEGF- and p53
      stained sections, the 2 markers were generally expressed in the same tumor cells.
      Of the 4 p53 gene mutations, 3 exhibited strong VEGF expression, and 1 exhibited
      moderate VEGF expression. VEGF expression did not correlate significantly with
      outcome variables in patients with squamous cell carcinoma. CONCLUSION: Our
      results suggest that VEGF expression is involved in the promotion of angiogenesis
      in cervical neoplasia and that p53 is likely to be involved in the regulation of
      VEGF expression.

PMID- 14714297
TI  - Fractal dimension rectified meter for quantification of liver fibrosis and other
      irregular microscopic objects.
AB  - OBJECTIVE: To introduce a new mathematical method based on the principles of
      fractal geometry analysis that permits more realistic quantification of some of
      the physical (morphologic) aspects of irregular bodies appearing under
      microscopy. STUDY DESIGN: The principles of the method were tested on microscopic
      images of irregular collagen deposition in liver tissue. The method uses an ad
      hoc rectified meter implemented in a computer-assisted planar image analysis
      system that has been adapted to give metric measures of irregular outlines and
      surfaces that can be used to produce an index capable of quantifying the typical
      wrinkledness of biologic objects. Prototypical example measures of liver fibrosis
      were made on biopsy specimens showing chronic hepatitis C virus-related disease.
      Measurements were also made of the microscopic images of the abnormal deposition
      of lipid droplets in hepatocytes, a case of amyloid deposition in an
      osteoarthromuscular structure and a cytologic specimen of human dendritic cells.
      RESULTS: The proposed computer-aided method permits rapid measurements of the
      image of a whole biopsy section digitized at high magnification. The snapshot
      measurement of liver fibrosis deposition offered by a biopsy pattern is a valid
      means of more rigorously identifying the staging of the process. CONCLUSION: This
      method can measure liver fibrosis during chronic liver disease as well as any
      other irregular biologic structure that cannot be correctly quantified using
      traditional Euclidean-based metric methodologies.

PMID- 14714298
TI  - Automated cell nuclear segmentation in color images of hematoxylin and eosin
      stained breast biopsy.
AB  - OBJECTIVE: To develop an automated, reproducible epithelial cell nuclear
      segmentation method to quantify cytologic features quickly and accurately from
      breast biopsy. STUDY DESIGN: The method, based on fuzzy c-mean clustering of the
      hue-band of color images and the watershed transform, was applied to 39 images
      from 3 histologic types (typical hyperplasia, atypical hyperplasia, and ductal
      carcinoma in situ [cribriform and solid]). RESULTS: The performance of the
      segmentation algorithm was evaluated by visually determining the percentage of
      badly segmented nuclei (approximately 25% for all types), the percentage of
      nuclei that remained in clumps (4.5-16.7%) and the percentage of missed nuclei
      (0.4-1.5%) for each image. CONCLUSION: The segmentation algorithm was sensitive
      in that a small percentage of nuclei were missed. However, the percentage of
      badly segmented nuclei was on the order of 25%, and the percentage of nuclei that
      remained in clumps was on the order of 10% of the total number of nuclei in the
      duct. Even so, > 600 nuclei per duct, on average, were segmented correctly; that
      was a sufficient number by which to calculate accurate quantitative, cytologic,
      morphometric measurements of epithelial cell nuclei in stained tissue sections of
      breast biopsy.

PMID- 14714299
TI  - Immunohistochemical expression of pi class glutathione S-transferase and alpha
      fetoprotein in hepatocellular carcinoma and chronic liver disease.
AB  - OBJECTIVE: To determine whether tumor marker pi glutathione transferase (GST-pi)
      is expressed in hepatocellular carcinoma (HCC) and other chronic liver diseases
      and to compare its expression with that of alpha-fetoprotein (AFP). STUDY DESIGN:
      Samples used were formalin-fixed, paraffin-embedded liver tissues: normal (n =
      3), chronic hepatitis B (n = 15), cirrhosis (n = 15) and HCC (n = 30). The
      expression of AFP and GST-pi was detected by using immunohistochemistry with the
      peroxidase-antiperoxidase method. AFP immunoreactivity was based on the cytoplasm
      of the hepatocytes, while GST-pi immunoreactivity was based on the nuclei of
      hepatocytes. RESULTS: In normal liver tissues, AFP was not expressed. However,
      there was strong staining of GST-pi in bile duct epithelium cells and weak
      staining in hepatocytes. Our results showed higher AFP immunoreactivity in cases
      of HCC (36.7%) as compared to cirrhosis (6.7%) and hepatitis B (0%), whereas GST
      pi immunoreactivity was lower in cases of HCC (53.3%) as compared to cases of
      cirrhosis (100.0%) and hepatitis B (93.3%). Percent sensitivity of AFP
      determination for HCC was 36.7% as compared to 53.3% for GST-pi, thus making GST
      pi a more sensitive marker for detection of HCC. This study showed a significant
      relationship between the intensity and percentage of cells stained in hepatitis
      B, cirrhosis and HCC for GST-pi immunoreactivity (P < .001, .001 and .05,
      respectively) but not for AFP (P > .05). Statistical analysis showed that there
      was no significant relationship between expression of AFP and GST-pi in cirrhosis
      and HCC cases. Hepatitis B virus infection in HCC cases showed a positive rate of
      46.7%, with AFP staining positively in 42.9% of tissues and GST-pi staining
      positively in 57.1% of tissues. CONCLUSION: AFP is a diagnostic but rather
      insensitive tissue marker for HCC. However, the absence of AFP in benign chronic
      liver disease makes this marker useful in differentiating between HCC and other
      chronic liver diseases, whereas GST-pi can be used as a diagnostic marker for HCC
      as well as in detecting other chronic liver diseases.

PMID- 14714300
TI  - A karyometric approach to the characterization of atypical endometrial
      hyperplasia with and without co-occurring adenocarcinoma.
AB  - OBJECTIVE: To develop a karyometric image analysis approach to distinguishing
      atypical endometrial hyperplasia with and without co-occurring adenocarcinoma.
      STUDY DESIGN: Six cases of atypical hyperplasia without and 6 cases with co
      occurring adenocarcinoma, 4 cases of normal endometrium and 3 cases of
      adenocarcinoma were identified. From each case 100 nuclei were measured in
      representative diagnostic areas identified by an experienced pathologist.
      Discriminant analyses were performed. An unsupervised learning algorithm was
      applied to define and characterize different nuclear phenotypes, and those data
      were used to identify cases with co-occurring adenocarcinoma. RESULTS:
      Discriminant analysis showed that nuclei from atypical hyperplasia and atypical
      hyperplasia with co-occurring adenocarcinoma are statistically different. The
      unsupervised learning algorithm revealed differences in nuclear subpopulations
      that can be used to correctly identify an estimated 85% of individual cases.
      CONCLUSION: Nuclei from atypical hyperplasia without and with co-occurring
      adenocarcinoma have statistically different karyometric characteristics that may
      facilitate case classification.

PMID- 14714301
TI  - AgNOR quantification in the diagnosis of follicular pattern thyroid lesions.
AB  - OBJECTIVE: To evaluate the usefulness of silver staining of nucleolar organizer
      regions (AgNORs) in the preoperative diagnosis of follicular lesions in the
      thyroid with computer-aided morphometric analysis of the silver dots. STUDY
      DESIGN: Forty-eight cytologic smears of the thyroid were divided into 3 groups
      according to the results of postoperative histopathologic examination:
      hyperplastic nodules in nodular goiter (NG) (20), follicular thyroid adenoma
      (FTA) (20) and follicular thyroid carcinoma (FTC) (8). They were silver stained.
      The slides were analyzed with a computerized system for image analysis. Nearly 20
      variables describing AgNORs were calculated (related to the area of the dots,
      number of dots and intranuclear localization of the dots). RESULTS: Only
      assessment of the total area of AgNORs in the nucleus allowed distinguishing
      between malignant and benign lesions. It was possible to determine the cutoff
      value of the total area of AgNORs in the nucleus (3.00 microns 2), limiting FTC
      from other lesions (observed ranges: NG, 1.64-2.87 microns 2; FTA, 1.81-2.85
      microns 2; FTC, 3.01-3.97 microns 2). Evaluation of the mean number of AgNORs per
      nucleus did not improve the diagnosis of malignancy. CONCLUSION: Computer-aided
      morphometric analysis of silver dots may be useful in the preoperative diagnosis
      of thyroid lesions.

PMID- 14714302
TI  - Karyometry of nuclei from actinic keratosis and squamous cell cancer of the skin.
AB  - OBJECTIVE: To use karyometric analysis methods to compare actinic keratoses (AKs)
      to squamous cell carcinomas (SCCs) to determine if SCCs showed a logical
      progression beyond that seen in AKs and to explore variability within and between
      lesion types to better understand distinctions between the 2. STUDY DESIGN:
      Biopsies from 31 subjects with AKs were obtained from upper inner arm skin,
      forearm skin and AK lesions. Biopsies from 23 different subjects in a related
      subproject provided SCC biopsies for comparison. RESULTS: Karyometric measures of
      nuclear abnormality and sun damage were derived. Mean actinic damage levels
      progressed logically from inner arm to sun-exposed skin, to AK, to SCC.
      Considerable heterogeneity existed at the case level. Unsupervised learning
      methods revealed 2 distinct clusters of progressed lesions with different nuclear
      signatures, reflecting differing levels of actinic damage. Number of AKs and SCCs
      and invasiveness and differentiation of SCCs were distributed across both
      clusters in roughly equivalent proportions. CONCLUSION: Karyometric methods,
      shown previously to be capable of sensitively detecting subtle nuclear changes,
      revealed the possibility of 2 progression pathways, each containing AKs and SCCs.
      This finding may have prognostic implications.

PMID- 14714303
TI  - [18FDG PET in the management of malignant lymphoma].
AB  - OBJECTIVE: To study the role and prospect of 18FDG PET imaging in patients with
      malignant lymphoma. METHODS: Forty-four patients (73 studies) with malignant
      lymphoma underwent 18FDG PET imaging. Final diagnoses were proved
      histopathologically. Images obtained were analyzed using visual and
      semiquantitative analysis (SUV). RESULTS: Either nodal or extranodal tumor foci
      showed high 18FDG uptake. 18FDG PET led to correct diagnosis in 5 of 6 cases
      except 1 false negative case. PET imaging changed the staging in 4 of 6 cases
      pretherapeutically. Of the 16 cases in which either residual tumor mass or
      suspicious recurrence suggested by other imaging modalities, 18FDG PET confirmed
      relapse in 5, detected more lesions in 2 and showed no evidence of active tumor
      mass in 9. For the 3 patients with comparison between pre- or post-treatment PET
      imaging and 16 patients who only underwent post-treatment PET follow-up studies,
      therapeutic response was correctly evaluated. CONCLUSIONS: 18FDG PET is a
      valuable non-invasive metabolic imaging modality in facilitating diagnosis and
      staging, evaluating therapeutic response, assessing clinical outcome and
      predicting prognosis in patients with lymphoma.

PMID- 14714304
TI  - [Recombinant replication-defective adenovirus based rabies vaccine].
AB  - OBJECTIVE: To construct and characterize recombinant adenoviruses containing
      glycoprotein (GP) gene from rabies virus CVS-N2C strain. METHODS: To obtain the
      recombinant adenovirus by pAdEasy system, identify recombinant virus with cDNA
      sequencing, Northern blot, Dot blot, Western blot and challenge-protection
      experiment of mice. RESULTS: Recombinant adenovirus showed typical adenovirus
      morphological characteristics; the viral genome was stable; GP specific mRNA and
      presence of glycoprotein were determined in rAdGPcvs and rAdGPcvs' infected
      cells. The glycoprotein produced by recombinant adenovirus had a molecular mass
      of 66,000, which was similar to that of natural glycoprotein. In the group of
      rAdGPcvs immunized mice, 87.5%-100% of mice survived from a 35.8LD50/38.0LD50
      lethal rabies intracerebral challenge. Finally 73.3%-83.3% of the mice that had
      received eAdGPcvs survived, and all the Ad5 immunized mice succumbed to rabies.
      CONCLUSION: Recombinant adenovirus rAdGPcvs and rAdGPcvs' hold great potential to
      be developed as recombinant rabies vaccines, and at the same time, it is actually
      the first study that on high neuropathogenicity rabies CVS-N2C glycoprotein based
      adenoviral recombinants.

PMID- 14714305
TI  - [Molecular mechanism of metastasis inhibition of nasopharyngeal carcinoma cell
      CNE-2L2 induced by reduction of 6A8 alpha-mannosidase expression].
AB  - OBJECTIVE: To study the effect of inhibition of 6A8 alpha-mannosidase expression
      on adhesiveness among and E-cadherin expression on CNE-2L2 cells, and on
      metastasis of the tumors from the cells inoculated in nude mice. METHODS:
      Anchorage-independent adhesion among cells was examined in soft agar culture. E
      cadherin expression was studied by immunofluorescence staining,
      immunohistological staining and RT-PCR. CNE-2L2 cells were subcutaneously
      inoculated into nude mice. Eight weeks later tumor metastasis was demonstrated by
      means of histological examination of lung sections. RESULTS: CNE-2L2 cells with
      suppression of 6A8 alpha-mannosidase expression (AS) became aggregated. E
      cadherin expression on wild type cells was very weak. In contrast, it was greatly
      enhanced on AS cells. The enhancement was detected on both protein and mRNA
      levels. Lung metastasis of the tumor from inoculated AS cells were heavily
      inhibited in nude mice. CONCLUSION: Inhibition of 6A8 alpha-mannosidase
      expression results in enhancement of cell-cell adhesion and of E-cadherin
      expression on CNE-2L2 cells. Lung metastasis of the tumor grown from AS cell
      inoculate in nude mice is heavily suppressed.

PMID- 14714306
TI  - [Manual microdissection of defined cells and RNA extraction for gene expression
      analysis of esophageal carcinoma progress].
AB  - OBJECTIVES: To isolate cells of interest from heterogeneous tissue blocks to
      obtain accurate representations of molecular alterations acquired by neoplastic
      cells so as to meet the demands of further study on gene expression patterns of
      the esophageal carcinoma (EC) evolution. METHODS: Blocks of EC were stored at -70
      degrees C as close as possible to the time of surgical resection. The tissue
      block was embedded in OCT and frozen sections of 35 microns in thickness were cut
      in a cryostat under strict RNAse-free conditions. Individual frozen sections were
      mounted on plain glass slides and 30-gauge needle attached to a 1 ml syringe was
      used to microdissect defined cells in the sections. The procured cells were used
      for total RNA extraction. RESULTS: An optimized protocol of manual
      microdissection was developed successfully whereby regions with an area as small
      as 1/25 mm2 could be accurately dissected. The RNA recovered from procured cells
      was of high quality suitable for subsequent applications of molecular analysis as
      assessed of 18S and 28S rRNAs by electrophoresis on agarose gel. CONCLUSIONS: It
      is believed that manual microdissection is capable to procure defined cell
      populations from complex primary tissues, thus allowing investigation of tissue-,
      cell-, and function-specific gene expression patterns. The technique is simple,
      easy to perform, versatile, and of particular usefulness when laser capture
      microdissection (LCM) is practically unavailable.

PMID- 14714307
TI  - [Identification of a novel mutation of C1 inhibitor gene in a Chinese family with
      hereditary angioedema].
AB  - OBJECTIVE: To identify the mutation of C1 inhibitor (C1 INH) gene in a Chinese
      family with hereditary angioedema (HAE). METHODS: Polymerase chain reaction and
      direct sequencing were used to identify the mutation type. The sequencing results
      were compared with the normal sequences in GenBank to find the mutation. In order
      to exclude the polymorphism, 30 normal volunteers were analyzed. RESULTS: One
      novel mutation (17839 del C) was detected in 5 patients with HAE. The mutation
      was not found in controls. CONCLUSION: The mutation of C1 INH gene (17839 del C)
      is identified in the family. Molecular diagnosis can be made by detecting the
      mutation.

PMID- 14714308
TI  - [Detecting HPV DNA in tissues of external genital squamous cell carcinoma in situ
      by PCR-RFLP technique].
AB  - OBJECTIVE: To study the relationship between the infection of human
      papillomavirus (HPV) and external genital squamous cell carcinoma in situ.
      METHODS: HPV DNA was detected with the consensus primer by polymerase chain
      reaction (PCR) and its type was determined by restriction fragment length
      polymorphism (RFLP). RESULTS: HPV DNA was detected and HPV16 was the most
      frequently identified type in 29 (56.9%) of 51 cases of external genital squamous
      cell carcinoma in situ. HPV DNA was positive in 22 (55%) of 40 cases of bowenoid
      papulosis, among which 20 were of HPV16 type, one of HPV31 type, and one of HPV6
      + 16 type. HPV DNA was positive in all 5 cases (100%) of Bowen's disease, among
      which 4 were HPV16 type and one of HPV6 + 16 type. HPV DNA was positive in 2
      (33.3%) of 6 Queyrat erythroplasia cases and all were of HPV16 type. CONCLUSION:
      HPV16 infection is strongly associated with the external genital squamous cell
      carcinoma in situ including bowenoid papulosis, Bowen's disease, and Queyrat
      erythroplasia.

PMID- 14714309
TI  - [Crosslinking bovine pericardial bioprosthetic heart valves by phthalocyanine
      sensitized photooxidation reaction].
AB  - OBJECTIVE: To crosslink bovine pericardial valves by phthalocyanine sensitized
      photooxidation reaction. METHODS: Fresh bovine pericardial tissues were immersed
      in PBS solution containing 0.01% cupreous sulfonatophthalocyanine and exposed to
      a broad wavelength light source for 20-120 h. Using sodium dodecyl sulfate
      polyarylamide gel electrophoresis (SDS-PAGE) to analyze the cross-linking extent
      of pericardial tissue. With the help of attenuated total reflection-fourier
      transform infrared (ATR-FTIR), explained the change of protein structure after
      photooxidation reaction. Differential scanning calorimetry (DSC) was used to
      measure the change of shrinkage temperature. Tissue water content experiment
      method was also used. RESULTS: Photooxidized tissue was resistant to extraction
      when it was compared with untreated tissue and had similar crosslinking extent
      over glutaraldehyde-treated tissue. The three dimension structure of collagen
      were changed but not seriously destroyed and the model of photooxidation reaction
      was validated. Phthalocyanine-treated tissue was much more flexible than
      glutaraldehyde-treated tissue. CONCLUSION: Bovine pericardial tissue can be
      successfully crosslinked by phthalocyanine-mediated photooxidation reaction.

PMID- 14714310
TI  - [Metabolic syndrome and latent autoimmune diabetes in adults].
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) in latent
      autoimmune diabetes in adults (LADA) and to study the positivity of glutamic acid
      decarboxylase autoantibody (GADA) in diabetic patients with MS. METHODS: Sera of
      598 patients with an initial diagnosis of type 2 diabetes (T2DM) were screened
      for GADA with radioligand assay. These patients were divided into LADA and T2DM
      groups according to the titers of GADA to compare the prevalence of MS; the
      proportions of LADA in diabetic patients with and without MS were studied. We
      also compared the clinical characteristics of LADA patients with and without MS.
      RESULTS: About 23.7% of the LADA patients had MS. In patients with MS, the
      prevalence of LADA was 10.0%, of which approximately 95% had low GADA titers,
      that was, belonging to LADA-type 2. Compared with LADA patients with MS, LADA
      without MS were similar to classical type 1 diabetes and had features of low body
      weight, tendency to develop ketosis and impaired islet cell function. CONCLUSION:
      About 23.7% patients with MS are found in LADA patients. The GADA levels in LADA
      patients with and without MS are significantly different, which may need
      different therapeutic strategies.

PMID- 14714311
TI  - [Cell biological mechanism involved in the effect of sodium selenite on improving
      insulin sensitivity].
AB  - OBJECTIVE: To study the cell biological mechanism of sodium selenite improving
      insulin sensitivity in pubertal rats with insulin resistance. METHODS: The
      content of inositol 1,4,5-trisphosphate (IP3) was examined by anion resin
      chromatography, and mRNA levels of phosphatidylinositol 3-kinase regulatory
      subunits (PI3Kp85 alpha) and Se-P were detected by RT-PCR in hepatocyte isolated
      from pubertal rats with insulin resistance. RESULTS: The mRNA levels of Se-P and
      PI3Kp85 alpha and content of IP3 in isolated hepatocyte decreased in pubertal
      male rats with insulin resistance. The above indices increased and reached normal
      level in rats supplied with selenium. The response to insulin stimulation in
      isolated hepatocyte in rats with selenium supply was similar to that in the
      control group, and both groups had higher response than those with high-fat diet.
      Alone when inhibited by wortmannin, the concentration of IP3 increased slightly
      in rats with selenium supply, but still was lower than that in the control group.
      CONCLUSIONS: These results indicate that the effect of selenium improving insulin
      sensitivity may be related to phosphatidylinositol PI3K signalling pathway. The
      effect of regulation of IP3 by selenium is not as effective as that by insulin,
      which may explain the difference of effect between selenium and insulin.

PMID- 14714312
TI  - [Application of intrapartum fetal oxygen saturation rate monitoring].
AB  - OBJECTIVE: To study the accuracy of the application of the intrapartum fetal
      oxygen saturation (FSO2) monitoring in predicting fetal acidosis and diagnosing
      intrauterine fetal distress. METHODS: Continuous FSO2 monitoring as well as
      internal and external fetal heart rate monitoring were applied respectively in 60
      women in labor during active phase of the first stage and the second stage. All
      the monitoring methods were validated with standard sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy on the bases
      of Apgar score and cord artery blood analysis. RESULTS: The mean FSO2 in the
      active phase of the first stage were significantly higher than in the second
      stage of labor. FSO2 correlated with pH, PO2, PCO2, and base excess (BE) of cord
      blood to a significant degree. There was linear correlation between FSO2 and cord
      artery blood pH. Using 30% cutoff diagnosing intrauterine fetal distress, the
      sensitivity, specificity, and accuracy were 80%, 100% and 98.3%, respectively.
      CONCLUSION: FSO2 monitoring is an effective method diagnosing intrauterine fetal
      distress.

PMID- 14714313
TI  - [Diagnosis and treatment of polypoid lesion of the gallbladder].
AB  - OBJECTIVE: To discuss the principles of diagnosis and treatment of the polypoid
      lesion of gallbladder. METHODS: Clinical and pathological features of 342 cases
      were analysed. RESULTS: Totally 328 patients with benign polypoid lesions
      (including 234 cholesterol polyps, and 74 adenomas), and 14 patients with
      malignant polypoid lesions (including 10 adenocarcinomas and 4 adenomas with
      malignant changes) were included. Two hundred and forty-seven cases (72.2%) had
      symptoms. Seventy-eight point six percent of patients with malignant polyps were
      over 50 years of age, and while 29.9 percent of patients with non-malignant
      polyps were over 50 years. The lesions were more than 1 cm in 91.7% of the
      malignant polyps and in only 13.2% of the benign polyps. One hundred percent of
      malignant polyps, and 46 percent of benign polyps were single polyp. CONCLUSIONS:
      Cholesterol polyps, adenomas, and adenocarcinomas are the most common lesions in
      polypoid lesion of the gallbladder. Cholecystectomy should be done in patients
      with symptoms. The risk factors for malignancy are the age of the patient (> 50),
      the size (> 1 cm), and number (single) of the polypoid lesions. In asymptomatic
      patients, cholecystectomy can be justified after integrated analysis.

PMID- 14714314
TI  - [Surgical management of metastatic disease in the conjunctive area between neck
      and thorax].
AB  - OBJECTIVE: To study the surgical management of metastatic disease in the
      conjunctive area between the neck and thorax and its efficacy. METHODS: Fourteen
      cases with metastatic node disease in the area between neck and thorax were
      collected and analysed. Eleven tumors were from the thyroid cancer, and the other
      three were from the hypopharyngeal cancer, esophagual cancer and malignant
      pheochromocytoma, respectively. The clavicle was displaced or resected, and the
      upper half of the manubrium might also be resected when necessary. The recurrent
      laryngeal nerve and phrenic nerve were exposed and protected. The metastatic
      disease was completely removed with the internal jugular and/or the
      brachiocephalic vein resected or spared, depending on the disease condition.
      RESULTS: In 10 cases with metastases from the thyroid, no local recurrence was
      found within the follow-up period from 2 to 5 years. In contrast, no patient with
      metastatic disease from hypopharyngeal or esophageal cancer survived more than 11
      months. No serious complications were found in this group. CONCLUSIONS: The
      surgical treatment of node metastases in the conjunctive area between neck and
      thorax from the well-developed thyroid cancer has promising effect and is
      comparatively safe.

PMID- 14714315
TI  - [Measurement of soluble CD44v6 in peripheral blood as assistant diagnosis of
      invasive pituitary adenomas].
AB  - OBJECTIVE: To investigate the value of measuring the concentration of soluble
      CD44 splice variant 6 (sCD44v6) in peripheral blood in patients with invasive and
      non-invasive pituitary adenomas. METHODS: The concentrations of sCD44v6 in
      peripheral blood were measured with ELISA in 68 patients with invasive pituitary
      adenomas and 100 patients with non-invasive pituitary adenomas. RESULTS: The
      serum concentration of sCD44v6 in patients with invasive pituitary adenomas was
      lower than that in patients with non-invasive pituitary adenomas, while the
      latter was lower than that in healthy controls. The serum concentrations of
      sCD44v6 were (44.63 +/- 7.21), (34.53 +/- 6.41), and (26.34 +/- 4.95) ng/ml in
      patients with invasive microadenoma, macroadenoma, and giant adenoma, and (60.78
      +/- 9.61), (57.78 +/- 10.00), and (37.22 +/- 5.17) ng/ml in patients with non
      invasive microadenoma, macroadenoma, and giant adenoma, lower than that in the
      healthy control group (68.73 +/- 6.00) ng/ml. Significant differences were
      observed among groups (P < 0.005). The concentration of sCD44v6 in peripheral
      blood decreased as the tumor size increased (P < 0.01), which was particularly
      significant in invasive pituitary adenomas. The positive rate in the patients
      with invasive pituitary adenomas reached 89.71%. CONCLUSION: Serum concentration
      of sCD44v6 in the peripheral blood is inversely correlated with tumor size and
      its invasive growth, which may provide certain value in the early diagnosis,
      treatment and prognosis of invasive pituitary macroadenoma and giant adenoma.

PMID- 14714316
TI  - [Evaluation of enzymatic method for determination of serum beta-hydroxybutyrate
      and its clinical application].
AB  - OBJECTIVE: To evaluate an enzymatic method for determining serum beta
      hydroxybutyrate (beta-HB) with the National Committee for Clinical Laboratory
      Standards (NCCLS) projects, and to discuss its clinical values in diabetic
      ketoacidosis (DKA). METHODS: The precision, accuracy, specificity, linearity and
      interference of the enzymatic method were analyzed. This method was used to
      determine serum beta-HB in 60 cases of normals, 50 cases of diabetes, and 34
      cases of DKA by autochemistry analyzer. RESULTS: Enzymatic beta-HB assay was
      precise (within-run CV, day-to-day CV, and total CV < 5%). The linearity studies
      showed the method was linear up to 4 mmol/L. Recovery rate was 98.5%-104.1%.
      Hemolysis (Hemoglobin up to 18.2 g/L), icteric samples with total bilirubin up to
      224 mumol/L, and lipemia up to triglyceride concentration of 2.28 mmol/L did not
      interfere with the beta-HB results in this method. Serum beta-HB levels were
      significantly elevated in DKA patients compared with DM patients and controls (P
      < 0.01). Positive rate of serum beta-HB in DKA patients was significantly higher
      than that of urinary ketone (P < 0.05). CONCLUSIONS: Enzymatic method is
      convenient and reliable, allows full automation, and is rapid enough to be used
      for both routine and urgent determinations of serum beta-HB. It can be used in
      diagnosing and monitoring treatment of DKA.

PMID- 14714317
TI  - [Hyperhomocysteinemia and deep-vein thrombosis].
AB  - OBJECTIVE: To study the relationship between plasma homocysteine (Hcy) level and
      deep-vein thrombosis (DVT), and analyze the interaction of Hcy, folate and
      methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with
      DVT. METHODS: Totally 69 patients with DVT and 111 healthy controls were included
      in our case-control study. We determined the MTHFR C677T genotypes by polymerase
      chain reaction and restriction fragment length polymorphism (PCR-RFLP), measured
      the serum folate and vitamin B12 by radioimmunoassay (RIA), and measured the
      plasma homocysteine level by fluorescence polarization immunoassay (FPIA).
      RESULTS: The frequency of the MTHFR C677T TT genotype had no significant
      difference between DVT group and control group (P > 0.05). The plasma Hcy level
      was significantly higher in DVT group than in control group (13.03 +/- 8.74
      mumol/L vs 10.14 +/- 4.30 mumol/L, P < 0.05). Both serum folate and VitB12 of
      patients with DVT were not significantly different from those of controls. The
      odds radios (OR) of hyperhomocysteinemia for DVT was 2.53 (95% CI 1.08-5.92). The
      interaction of low folate level and TT genotype increased the risk of DVT (OR =
      3.12, 95% CI 1.17-8.38). CONCLUSION: Hyperhomocysteinemia may be an independent
      risk factor for DVT in Han nationality, while serum folate level and MTHRF C677T
      genotype are not. An interaction between serum folate level and MTHFR genotype
      that affect the Hcy level is an important risk factor for DVT.

PMID- 14714318
TI  - [Combined analysis of urinary stones by X-ray photoelectron spectroscopy and X
      ray powder diffraction].
AB  - OBJECTIVE: To seek the methods in the prevention and cure of urinary stones in
      the Zhujiang valley in Guangdong province. METHODS: Twenty random urinary stones
      were quantitatively and morphologically analyzed by X-ray photoelectron
      spectroscopy (XPS) and X-ray powder diffraction (XRD). RESULTS: Calcium oxalate
      (about 70%) was the main composition of urinary stones in the Zhujiang valley in
      Guangdong province; while 30% of which was uric acid stones. Most calcium oxalate
      stones contain phosphate; however, its content usually was less than 10%.
      CONCLUSIONS: Calcium oxalate, uric acid and phosphate are the main compositions
      of urinary stones in the Zhujiang valley in Guangdong province. The compositions
      and phases of urinary stones can be obtained accurately by the combination of XPS
      and XRD.

PMID- 14714319
TI  - [Variations of protein concentration in saliva stimulated and its effect on
      clinical diagnosis].
AB  - OBJECTIVE: To study the variations of protein concentration in saliva stimulated
      and its effect on clinical diagnosis. METHODS: The saliva from 33 normal controls
      and 73 patients with Sjogren syndrome (SS) who were stimulated with acid and not
      were collected. The concentration of beta 2 microglobulin (beta 2-mG), secretory
      immunoglobulin A (SIgA), and pH were measured by Radioimmunoassay, Rate
      Nephelometry and pH Detection Paper, respectively. SPSS 10.0 was used to
      determine the mean statistical differences among these groups. RESULTS: In
      patients with SS, the concentration of beta 2-mG in saliva stimulated with Vc was
      significantly lower compared with that in saliva not stimulated (P < 0.01); In
      saliva stimulated with Vc, the concentration of beta 2-mG in patients with SS was
      higher than that in normal controls (P < 0.05). In normal controls, compared with
      that in saliva not stimulated, flow rate in saliva stimulated with 3% acetic acid
      and Vc was significantly higher (P < 0.01) and pH, concentration of beta 2-mG and
      SIgA were significantly lower (P < 0.01 and P < 0.05 respectively); there was a
      significant difference of flow rate, beta 2-mG, SIgA and pH in saliva between the
      subjects stimulated with 3% acetic acid and with Vc (P < 0.01). CONCLUSIONS: The
      reason for the decrease of protein concentration in saliva stimulated may be the
      increase of flow rate caused by the decrease of pH or the decrease of pH itself.
      Protein detection of saliva stimulated in patients with SS is helpful in
      diagnosis, but the criterion is different between the saliva stimulated and not
      stimulated.

PMID- 14714320
TI  - [Application of imaging postprocessing of thoracic spiral CT].
AB  - OBJECTIVE: To evaluate the clinical values of spiral CT imaging postprocessing
      techniques. METHODS: Totally 167 patients with known or suspected abnormalities
      of thorax (including small pulmonary emboli, primary and metastatic tumours,
      diffuse lung diseases, bronchiectasis and emphysema) underwent spiral CT of their
      thorax. We reconstructed images by using different postprocessing techniques
      (MPR, MIP, SSD, VR, STS and VE). Images after postprocessing were reviewed in
      conjunction with axial CT scans by three readers with specific focus on their
      diagnostic and therapeutic efficiency. Judgement was reached by consensus.
      RESULTS: Compared with axial CT scans, image presentation after postprocessing
      (a) corrected interpretive errors in 15 cases; (b) raised diagnostic confidence
      by providing supplemental diagnostic and/or morphologic information in 57 cases;
      (c) assisted the accurate location of complicated sites in 9 cases; (d) played a
      major role in therapy planning in 75 cases; and (e) was not associated with
      diagnostic superiority in 11 cases. CONCLUSION: Postprocessing of spiral CT data
      can represent a useful complement to axial CT in most patients with thoracic
      diseases and should be a routine part of radiological practice.

PMID- 14714321
TI  - [Diagnosis and misdiagnosis of adrenoleukodystrophy: a causal analysis].
AB  - OBJECTIVE: To discuss the diagnosis of adrenoleukodystrophy(ALD) and analyse the
      causes of its misdiagnosis. METHODS: The clinical and laboratory data of six
      cases with ALD were analyzed. RESULTS: Among the six cases of ALD, 4 cases were
      of childhood cerebral ALD, 1 case of Addison only, and 1 case of adolescent
      cerebral ALD. Pigmentation of skin was the first symptom in 3 cases. The delay
      from the diagnosis of Addison's disease to that of ALD ranged from 1 to 6 years.
      Another 2 cases was misdiagnosed as multiple sclerosis in early stage.
      CONCLUSION: The most important reason of delay is that the physician is
      unfamiliar with the ALD clinical features. Assay of very long chain fatty acid
      (VLCFA) is useful for the early diagnosis of ALD.

PMID- 14714322
TI  - [Serum anti-titin antibody in patients with myasthenia gravis].
AB  - OBJECTIVE: To study the clinical significance of serum anti-titin antibody level
      in the diagnosis of myasthenia gravis (MG) with thymoma. METHOD: The serum anti
      titin antibody was analysed by ELISA method in 40 cases of health control group,
      90 cases of MG, 17 cases of MG with thymoma and 7 cases of no-MG thymoma. The
      positive rate was compared among these groups. RESULTS: The positive rate of anti
      titin antibody was significantly higher in MG with thymoma patients than MG
      patients (94% and 3%, P < 0.01). According to the Osserman's classification, anti
      titin antibody was present mostly in patients (43%) in IV stage, and also present
      in 2 cases of 7 who with no-MG thymoma. CONCLUSION: Serum anti-titin antibody
      test is helpful in the diagnosis of MG with thymoma.

PMID- 14714324
TI  - [Anterior thoracoscopic approach of thoracic spine in adolescent idiopathic
      scoliosis].
AB  - The use of anterior surgical techniques for the treatment of adolescent
      idiopathic scoliosis (AIS) has increased recently and anterior discectomy,
      anterior release and fusion, instrumentation of the thoracic scoliosis can be
      performed through a thoracoscopic approach. The thoracoscopic approach has
      several advantages: small surgical trauma, early return to work, reduced
      postoperative pain and improved postoperative respiratory functions. Although the
      thoracoscopic approach still has some shortcomings currently, it will be widely
      accepted with further development of this technique and instrumentations in the
      future.

PMID- 14714323
TI  - [Radionuclide reporter gene imaging].
AB  - Molecular nuclear imaging techniques are currently being developed to map the
      topography and level of gene expression following gene therapy. To date, two
      radionuclide-based imaging strategies have been investigated--using reporter
      genes encoding either intracellular enzymes or cell-surface receptors. In this
      article, we discuss these two reporter gene imaging systems that have been
      developed to detect gene expression noninvasively.

PMID- 14714325
TI  - [Using chemical methods to crosslink xenogeneic heart valves: the progress of
      bioprosthetic heart valves].
AB  - Glutaraldehyde clinically is the most commonly accepted crosslinking reagent for
      bioprosthetic valves preparation. Glutaraldehyde-treated tissue is stable against
      chemical and enzymatic degradation; however, its calcification and cytotoxicity
      are severe. Dye-mediated photooxidation is an alternative tissue preservation
      method that oxidizes the protein with visible light in the presence of a suitable
      photosensitizer. This article reviews chemical mechanism, research progress,
      clinical applications future development of these two methods.

PMID- 14714326
TI  - [A mathematical model of the behavior formation in mastering the determinate
      patterns of stimuli].
AB  - The paper deals with studying and with analyzing a variety of mathematical models
      designed for constructing the behavior under the conditions of mastering the
      determinate patterns of stimuli. Models of random reaction choice and of random
      strategy choice are viewed as basic ones. A two-parameter model designed for
      shaping a strategy choice was investigated and suggested. The model describes a
      strategy choice on the basis of commemorating the previous experience with regard
      for an intensity of forgetting the mastered experience and on the basis of an
      independent and spontaneous shaping of patterns. The model was used to interpret
      the changes, observed in the behavioral indices of patients with schizophrenia
      and oligophrenia versus the virtually healthy subjects, as changes of
      actualization of applying the previously mastered experience and those of the
      forgetting speed up.

PMID- 14714327
TI  - [The stability of the vertical posture in children with attention deficit
      syndrome with hyperactivity and its psychophysiological maintenance].
AB  - Described in the paper are the results of studying the functional balance system
      and the specificity of the psychological-and-physiological maintenance of the
      vertical posture in different positionings in 560 children, aged 7 to 10, with
      the syndrome of attention deficit and with hyperactivity (SADHA). The prevalence
      of SADHA was analyzed by questioning the parents and teachers and by
      psychophysiological testing. It was established that an impaired stability of the
      vertical posture and an impaired development of co-ordination abilities are
      typical of SADHA children; it is preconditioned by a changed regulatory influence
      of big cortex hemispheres on the subcortical structures, which is confirmed by a
      deranged energy status of the brain. Finally, a higher tonus is registered in
      both the sympathetic and parasympathetic sections of the vegetative nervous
      system.

PMID- 14714328
TI  - [The determination of the sensitivity and specificity of the interpretation rules
      parameters in a study of the medical equipment testing].
AB  - The interpretation systems of medical instruments are traditionally assessed by
      their sensitivity and specificity in definitions of the binary classification
      scheme. However, should the system's conclusions on the presence of a pathology
      be extended by a multitude of degrees of its pronouncement, such scheme is
      unacceptable. A three-digital classification scheme with isolated degrees of
      pronounced and weak pathology signs reflects, firstly, an understanding of the
      interpretation error value between these two degrees and, secondly, the
      harmlessness of errors inside each degree. The discussed logical and
      probabilistic models of constructing the quality parameters ensure the continuity
      in respect to the indices of the binary classification scheme, however, it can be
      stated that the probabilistic parameters are more preferable.

PMID- 14714329
TI  - [A description of electrophysiological parameters in children and teenagers with
      diabetic peripheral polyneuropathy].
AB  - Two hundred and ninety patients with diabetes mellitus, type 1, aged 5 to 18,
      disease duration--1 to 15 years, were examined at the chair for endocrinology of
      children and teenagers of of the Russian Medical Academy for Postgraduate
      Training of the Ministry for Health of the Russian Federation. The purpose of the
      case study was to investigate the electromyogram (EMG) parameters in such
      patients with respect to the disease duration, carbon metabolism compensation,
      age specificity and a stage of diabetic peripheral polyneuropathy (DPP). The
      results primarily denote a lesion in the axons; the pronounced demyelinating
      process in peripheral nerves of children and teenagers with DPP is highly
      possible. The obtained data is suggestive of the feasibility to recommend the
      stimulation EMG method for a comprehensive use in the diagnostics of pre-clinical
      DPP stages in children and teenagers, for evaluating a severity of the damage to
      peripheral nerves in DPP of symptom-types forms as well as for a dynamic follow
      up of patients and for treatment efficiency evaluation.

PMID- 14714331
TI  - [An analysis of the gait in patients with different type of infantile cerebral
      paralysis].
AB  - The issue related with impaired temporal movements as observed in patients with
      infantile cerebral paralysis (ICP) during walking still needs more research since
      it is a vital problem. The authors analyzed the temporal parameters of the step
      and of the phase of the key goniography spots within the stretch of the step
      cycle. The results are indicative of a presence of specific gait temporal indices
      typical of all ICP variations; they also reveal such indices typical of a certain
      disease type. The use of biochemical investigations of temporal parameters of the
      step and movements in legs' joints makes it possible to verify the available
      motor impairments and to carry out the differential diagnosis of different-type
      ICP.

PMID- 14714330
TI  - [The dynamic range of a digital X-ray diagnostic system operating in a counting
      mode].
AB  - A method is described in the paper that is designed to assess the values of the
      dynamic range of digital X-Ray diagnostic systems operating in the counting mode.
      The dynamic range is shown to be determined from the bottom by static limitations
      of the image quality, while from the top it is determined by system's counting
      errors caused by the terminal temporal resolution.

PMID- 14714332
TI  - [Mathematical processing of the keratograms].
AB  - The paper deals with the mathematical processing of keratograms of a new
      keratoscope designed by the authors. A method of describing the curve of the
      corneal surface section (to a certain degree) by polynomial is under
      consideration; the method's accuracy is assessed. The calculations' results
      reveal a practical suitability of the methods for measuring and for the
      mathematical processing of keratograms.

PMID- 14714333
TI  - [A comparative analysis of the two approaches to the evaluation of thrombogenic
      qualities of the biomaterials in vitro].
AB  - The paper contains an analysis of thrombogeneticity of biomaterials in vitro with
      regard for the changing time of recalcification of the platelet-free and platelet
      related human blood plasma after incubation with a studied sample. Two sizeless
      thrombogeneticity parameters are suggested for describing the thrombogeneticity
      of studied biomaterials irrespective of a incubation-medium composition. It was
      demonstrated by the example of glass granules, which were modified by various
      immobilized functional groups, that the measuring of re-calcification time
      performed after samples' incubation secures a more objective assessment of
      platelet-resistant properties of materials. The relative index of
      thrombogeneticity of biomaterials (with the above glass granules being the
      controls), unlike the standardized parameter, opens up the possibility to study
      comparatively the activating action exerted on the coagulating and anti
      coagulating blood systems of the studied samples, which differ by the ratios of
      their surface squares to the incubation-medium volume.

PMID- 14714334
TI  - [Designing and manufacturing and supplying the instruments and equipment to
      medical facilities by ZAO "VNIIMP-VITA" RAMH in 2002 and 2003].
AB  - Outlined in the paper are some essential aspects related with the activity
      results of the All-Russia Research Institute for Medical Instrument-Making Ltd.
      of the Russian Academy of Medical Sciences, as of the leading Russian institution
      in the field of medical instrument-making. Data are described on a variety of
      already manufactured and on some new medical equipment items now in the process
      of designing.

PMID- 14714335
TI  - [The problems of the modern electrocardiography (to the 100th anniversary of
      electrocardiography, 1903-2003)].
AB  - Elucidated in the paper are the key issues of modern electrocardiography (ECG).
      The negative results of large-scale use of automated ECG interpretation programs
      are under discussion. The possibility of removing the analogue filters from the
      electrophysiological apparatus and replacing them with the digital signal
      processing equipment is contemplated. The modern ECG examinations can not exist
      without simple automation the program security of information processing. The
      results of introducing the or apparatus-program complexes (APC) into practice as
      auxiliary analysis instruments in ECG are analyzed. The effects of APC
      introduction into daily ECG practice are shown to be advantageous. Finally, there
      is an analysis of issues related with global computerization in clinical
      examinations.

PMID- 14714336
TI  - [Medical equipment. Tilting beds. Condition and perspectives].
AB  - Data are elucidated in the paper on the tilting beds available in the Russian
      market. There is a sufficiently detailed description of the discussed products
      manufactured by Russian and foreign companies. Prospective requirements of more
      comfort for the patient are outlined.

PMID- 14714337
TI  - [The development of medical information consulting systems].
AB  - A model of an information-and-consultative system (ICS) designed for
      practitioners and students in the field of pulmonology at the Research Institute
      for Pulmonology of the Russian Academy of Medical Sciences (project director-
      A.G. Chuchalin) is outlined in the paper. The purpose was to construct an ICS
      structure that would be adapted to continuously increasing and changing knowledge
      in the field of pulmonology and that could be used to interpret such knowledge
      from the standpoint of medical proof.

PMID- 14714338
TI  - [KRT-"Electron" remote control X-ray equipment complex].
AB  - The paper contains data on the remote control X-ray diagnostic sets designed, in
      Russia, by the "Electron" Research and Instrument-Making Co. Ltd.

PMID- 14714339
TI  - [Hospital 2007: ... and the cardiology?].

PMID- 14714340
TI  - [The transfer of capacities in cardiology: is it the solution to coming
      difficulties in terms of medical demography that the French general hospitals
      will have to face in their departments of cardiology?].

PMID- 14714341
TI  - [Brain natriuretic peptide, heart failure and elderly patients].
AB  - Natriuretic Peptides like BNP or NT Pro BNP are diagnostic and prognostic makers
      largely used in clinical practice. Ageing may increase these peptides, especially
      in case of comorbidities like renal failure or hypertension and require
      adjustment for age. Diagnostic value of natriuretic peptides seems however
      preserved in elderly people.

PMID- 14714342
TI  - [Anticoagulation of valvular prostheses].
AB  - Prosthetic valve replacement has transformed the outcome of patients with severe
      or poorly tolerated valvular heart disease. Between the two main families of
      prostheses, only mechanical prostheses require indefinite anticoagulant therapy
      to lower the thromboembolic risk. National and international guidelines have been
      published within the past decade. They have outlined how anticoagulation,
      essentially oral anticoagulant therapy and transient heparin, should be used. The
      intensity of anticoagulation depends on the type of prosthesis, its position, the
      presence of atrial fibrillation and the individual's risk of thromboembolism.
      Monitoring is based on the INR. Temporary recourse to heparin therapy is
      necessary for all situations in which the risk of major hemorrhage requires more
      flexible treatment (postoperative period, extracardiac surgery, stroke, severe
      hemorrhage) or when warfarin is contraindicated because of its risk of inducing
      malformation (pregnancy). Low molecular weight heparins are not yet authorized
      for use in prosthesis bearers. Nonetheless, they are being prescribed by more-and
      more teams, seduced by the facility of their use, their more stable action and,
      usually, no need for biological monitoring. And their use is supported by the
      most recent guidelines, several favorable publications, and the excellent results
      obtained with them in treating other thromboembolic pathologies. Indispensable to
      lower the rate of thromboembolic events, anticoagulant therapy bears a
      hemorrhagic risk that is higher for prolonged and marked anticoagulation. On the
      other hand, despite effective anticoagulation, the occurrence of thromboemboli
      can lead to considering the adjunction, in certain cases, of anti-platelet
      aggregating agents, particularly favored in North America, and recommended in
      Europe for patients with a predilection for atheromas.

PMID- 14714343
TI  - [Evaluation of an education program of patients undergoing oral anticoagulation
      treatment].
AB  - OBJECTIVE: To evaluate the therapeutic impact of an education program on patients
      undergoing oral anticoagulation treatment, within the hospital of Annecy
      (France). MATERIAL AND METHODS: Groups of 10 patients were invited to participate
      to two meetings. The education was carried out by two nurses. Thanks to this
      prospective study, we compare the population before and after education in terms
      of treatment knowledge and stability. RESULTS: Within 9 months 88 patients have
      been included, amongst which 55 have attended the two meetings. The average of
      correct answers to the knowledge evaluation questionnaire distributed before and
      after 6 months of education were, respectively, 6.63/12, 10.09/12 (P < 0.0001).
      Through INR controls within the 6 months preceding (424 controls) and the 6
      months following the education (619 controls), we observe: an increase of the
      total INR average in therapeutic zone, from 45% to 61% (P < 0.0001); a decrease
      of the difference average per patient between the INR value observed and the one
      targeted: 0.54 before education, 0.40 after education (P = 0.0016); at last, the
      average phasing per patient under the therapeutic zone increases after education,
      from 49% to 65% (P < 0.001). CONCLUSION: The education improves objectively the
      knowledge of patient undergoing AVK. If the size of patient sample is not large
      enough to prove any consequence on hemorrhagic or thrombotic complications, the
      education program still improves significantly the treatment stability.

PMID- 14714344
TI  - [Is there an increased risk for cardiovascular disease in HIV-infected patients
      on antiretroviral therapy?].
AB  - There is a growing concern about an increased risk for cardiovascular disease in
      HIV infected patients receiving antiretroviral therapy (ART). This risk could be
      related to metabolic abnormalities associated with long-term use of
      antiretroviral drugs. In fact, well recognized cardiovascular risk factors such
      as hypertension, dyslipidaemia, diabetes mellitus and central fat deposition are
      increasingly seen in HIV patients on ART. These factors can also be associated
      with non reversible risk factors, such as male sex, age greater than 40 years and
      family history of premature coronary artery disease. In addition, cigarette
      smoking and sedentary lifestyle may predispose these patients to significant
      cardiovascular disease. A direct atherogenic effect of HIV infection itself or
      antiretroviral drugs is unlikely. Epidemiological studies have suggested an
      increased risk for coronary artery disease in HIV infected persons; nevertheless,
      only long term follow-up could confirm this statement. Despite these
      uncertainties, it seems reasonable to identify and manage cardiovascular risk
      factors in HIV infected patients.

PMID- 14714345
TI  - [Precipitating factors associated with diastolic heart failure in the elderly].
AB  - BACKGROUND: Beside basal myocardial dysfunction, acute heart failure involves
      associated factors, which increase pulmonary capillary pressure or decrease
      colloid osmotic pressure. The aim of this study was to evaluate the prevalence of
      these precipitating factors in a population presenting with acute heart failure
      with preserved left ventricular systolic function. METHODS: Forty-eight patients
      (25 men, 78 +/- 10 years) presenting pulmonary edema with a left ventricular
      ejection fraction > 45% were included. All had a Doppler echocardiography at the
      time of intravenous loop diuretics initiation. Patients with severe valve disease
      or symptomatic coronary disease were excluded. RESULTS: A history of heart
      failure, coronary disease, hypertension and diabetes was present in 62%, 42%, 64%
      and 33% of patients, respectively. On admission, mean left ventricular ejection
      fraction was 61 +/- 9% and 79% of patients had critical elevation in Doppler
      filling pressures. Associated factors were renal failure (creatinine clearance <
      30 ml/min) in 33% patients, silent myocardial ischemia (troponin I > 0.5 ng/ml)
      in 31%, atrial fibrillation in 29%, high systolic blood pressure (> or = 160
      mmHg) in 27%, major sepsis in 25%, severe hypoalbuminemia (< or = 2.5 g/dl) in
      23%, and severe anemia (< 10 g/dl) in 17%, respectively. Four patients had no
      aggravating factor, whereas 34 and 10 patients had 1-2 and 3-4 associated
      factors, respectively. CONCLUSION: Besides diastolic dysfunction, factors leading
      to a critical decrease in the oncotic pressure such as pulmonary capillary
      pressure gradient are found in most of the elderly patients presenting acute
      diastolic heart failure and must be checked systematically.

PMID- 14714346
TI  - [Reflux nephropathy and arterial hypertension].
AB  - This case-report emphasizes an uncommon cause of hypertension in an adolescent:
      reflux nephropathy. Reflux nephropathy is a frequent hypertension and renal
      failure etiology. Medical treatment is unknown from cardiologist.

PMID- 14714347
TI  - [Pacemaker syndrome after dual-chamber implantation: consequence of a very long
      atrial activation delay].
AB  - Many circumstances, generally occurring in inappropriate device's adjustment or
      in specific myocardial conduction's disturbances, can result in dual chamber
      indications in pace maker syndromes. Our case report is about a man implanted
      with a dual chamber device with a dilated right atrium and intra atrial
      conduction delay resulting in a delayed post pacing atrial activation time. The
      consequence was an atrial contraction occurring during closed atrioventricular
      valves.

PMID- 14714348
TI  - [Non-invasive coronarography: myth or reality].
AB  - Slice Imaging technology progress allows a good approach of coronary arteries.
      MRI and Multislice Computed Tomography (MSCT) are in competition. Inspite of
      important progress, MRI of coronary artery disease remains "disappointing". With
      this imaging technology, there is a good plaque burden and myocardium
      visualisation. MST, and particularly with 16 slice technology, allows a good
      coronary stenosis identification. This technology enables soft plaque and
      myocardial ischemia detection. It is now possible to detect coronary heart
      disease with MSCT, which can replace or help a coronary angiogram in some
      indications.

PMID- 14714349
TI  - [Educating patients about heart failure in community hospitals: it is
      possible...].
AB  - Prognosis for heart failure is linked to patient's compliance. Compliance is also
      dependent from patient education about his disease and treatment. Therapeutic
      education could be done in a community hospital but needs a lot of time. However,
      therapeutic education for heart failure patients becomes more and more essential
      in clinical practice and improves patient knowledge and implication and
      hospitalization duration.

PMID- 14714350
TI  - [FACT: French national registry of acute coronary syndromes. Specific study of
      French general hospital centers].
AB  - The FACT registry is currently the French registry including the greatest number
      of patients with acute coronary syndromes. PURPOSE: The study presents
      epidemiologic data, modalities and delays for medical admission. METHOD: Three
      thousand nine hundred and two patients were included in FACT by 362 French
      centers of cardiology between 06/01/2003 and 03/02/2003. One thousand eight
      hundred and ten patients, who had been placed in the cardiology departments of
      French general hospitals, were isolated from this registry. The French general
      hospitals represented 50.8% of the 362 centers. In order to clarify the study,
      these patients were divided into three groups: group A: patients without ST
      segment elevation but with suggestive ECG modifications; group B: patients with
      ST segment elevation; group C: all other patients. The results were mainly
      studied for groups A and B and compared. These results were also compared to
      those of the FACT registry and of other registries. RESULTS: The results show
      that the average delay for admission is 2.9 h after a first delay between the
      pain and the help of 6.7 h. The first intervening party is a general practitioner
      (36.4%) then the SAMU (31.6%) and finally the emergency departments (18.7%).
      16.6% of the patients from group B undergo pre-hospital thrombolysis. The
      recommendations of the European Society of Cardiology are widely applied except
      for the most recent of them since only 27.6% of the patients from group A having
      a TIMI score > or = 5 receive an anti-GIIB IIIA treatment. The reasons of the non
      prescription of the recommended classes are mostly linked to contra-indication
      and intolerance. The strategy of coronary reopening mainly depends on the
      presence or the absence in the department of an available medical equipment for
      angioplasty. If there is one, the percentage of primary angioplasty reaches 54.2%
      and the percentage of thrombolysis 7.9%. On the opposite, there is 8.3% of
      angioplasty and 54.2% of thrombolysis for the unequipped centers. The global
      mortality reaches 5.8% but is inversely proportional to the level of equipment of
      the departments: 5.9% for the departments with angioplasty, 11% for the
      departments with coronarography but without angioplasty and 13.8% for the
      departments without any interventional equipment. Nevertheless, the age of the
      patients is different and this influences the results: we notice that the less
      equipped the department is, the older the patients are. CONCLUSION: The FACT
      registry and the data from the general hospitals give the opportunity to think
      about the possibilities to improve the delays of call to the first intervening
      party (more particularly to the SAMU) but it also allows us to think about how to
      better organize the geographical distribution giving access to a medical
      equipment for angioplasty. All these information will also help the cardiologists
      to gather around the recommendations by convincing them that the benefit/risk
      ratio is positive.

PMID- 14714351
TI  - [Primary cardiogenic shock in the acute phase of myocardial infarction treated by
      angioplasty: experience of three non-university public centers in Alsace].
AB  - OBJECTIVE AND METHOD: Evaluation of angioplasty for primary cardiogenic shock in
      acute myocardial infarction in three non-universitary alsacians centres between
      1999 and 2002. RESULTS: One hundred and eighty-two patients were included.
      Hospitalisation survival rate is 43.96% after hospital discharge. One hundred and
      forty-nine patients were treated by primary angioplasty. Angioplasty is
      successful in 79.12%. The predictives factors of death are: age > 75, TIMI = 0 at
      the admission, three vessels disease. Twenty-four months survival is 91% (follow
      up data available on 28.75% of the patients alive at hospital discharge).
      CONCLUSION: Angioplasty seems to be the right choice in case of acute myocardial
      infarction complicated by cardiogenic shock, the results are better than medical
      treatment at short- and mid-term.

PMID- 14714352
TI  - [Clinical research in community hospitals in France].
AB  - Medical research is an important part of medical art. From Hippocratis to
      hypothesis ... resume research processes. Medical trials could be done or managed
      by community hospitals but it implies several collaborations with university
      structures. Even it is sometimes difficult to do, improvement of medical science
      and patient management through publications and communications are the ultimate
      goal of such trials....

PMID- 14714353
TI  - [Analysis on the dependence and intention of experimental randomized controlled
      therapy].

PMID- 14714354
TI  - [Effect of acupuncture-drug compound anesthesia on alteration of immune function
      in patients undergoing open-heart surgery].
AB  - OBJECTIVE: To observe the effect of electro-acupuncture (EA) on alteration of
      immune function of patients undergoing open-heart surgery with cardiopulmonary
      bypass (CPB), and to appraise the value of acupuncture-drug compound anesthesia
      in the operation. METHODS: Thirty patients undergoing atrial septal defect
      repairing operation were selected and divided into three groups, Group A was the
      general anesthesia group; Group B, the acupuncture anesthesia group and Group C,
      the general anesthesia plus EA group. Peripheral venous blood of patients was
      collected at different time points, i.e. before anesthesia, before CPB, 30 min
      and 24 hrs after CPB, to determine natural killer cells activity (NKCA), and the
      levels of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in supernatant of
      cell culture were also tested. RESULTS: NKCA was significantly lowered in Group A
      before CPB but increased in Group B, while no evident change was found in Group
      C, so the level of NKCA in Group B was significantly higher than in the other two
      groups. It lowered in all the three groups after CPB, especially evidently in
      Group B, so as to cause the NKCA level in Group B lower than that in Group A. The
      lowering further progressed, 24 hrs after CPB, NKCA in Group B was more reduced
      than that in Group C. Levels of IFN-gamma and IL-2 lowered in all the three
      groups after CPB, and further lowered at time point of 24 hrs after CPB, but the
      parameters in Group C were significantly higher than those in Group B.
      CONCLUSION: EA could enhance NKCA, but acupuncture anesthesia couldn't inhibit
      the suppressive effect of CPB on NKCA, IL-2 and IFN-gamma, suggesting that the
      immunosuppression induced by stress has a prior effect. General anesthesia plus
      EA yielded better effect than general anesthesia and acupuncture anesthesia, but
      it could't improve the immunosuppression completely, indicating that the compound
      anesthesia could partially improve the immunosuppression induced by CPB.

PMID- 14714356
TI  - [Summary of academic symposium on integrative medicine between Taiwan and the
      mainland].

PMID- 14714357
TI  - [Myocardial protection and mechanism of Puerarin Injection on patients of
      coronary heart disease with ischemia/reperfusion].
AB  - OBJECTIVE: To explore the protective effect and the mechanism of Puerarin
      Injection (PI) on myocardial ischemia reperfusion in patients with coronary heart
      disease (CHD) and angina pectoris (AP). METHODS: Seventy-eight patients with AP
      planned to receive the PTCA and stenting treatment were randomly divided and
      single-blindedly into the conventional group and the PI group. Based on the
      conventional treatment and pre-operational preparation, the PI group was given
      200 ml of PI by intravenous dripping once a day, beginning from one week before
      operation, but to the conventional group, normal saline was given for instead.
      The condition of AP attack in balloon dilatatory stage of PTCA was observed and
      change of ST segment of ECG detected by a 12-lead ECG monitor. The blood levels
      of von Willebrand factor (vWF:Ag), nitric oxide (NO) and endothelin-1 (ET-1) were
      also observed before and after treatment. RESULTS: As compared with those in the
      conventional group, number of patients having AP attack and ST segment change in
      PTCA process was lessened in the PI group, with blood levels of vWF:Ag and ET-1
      obviously lower, and NO content obviously higher than those in the conventional
      group, CONCLUSIONS: PI could protect the myocardium in 2-3 days after ischemia
      reperfusion, one of the possible reasons is that PI can simulate the late phase
      of ischemic preconditioning, which may be related to its effect in lowering
      plasma vWF:Ag and ET-1, and increasing the serum NO content.

PMID- 14714355
TI  - [Effect of Milkvetch Injection on cardiac function and hemodynamics in children
      with tetralogy of Fallot after radical operation].
AB  - OBJECTIVE: To evaluate the effect of Milkvetch Injection (MI) on cardiac function
      and hemodynamics in children with tetralogy of Fallot after radical operation.
      METHODS: Thirty-two children with tetralogy of Fallot were divided into two
      groups, the 20 patients in the control group treated with conventional treatment
      and the 12 patients in the treated group treated with 15 ml of MI every 12 hrs
      for 7 days. The cardiac function and hemodynamic parameters were determined by
      echocardiography and thermodilution catheter inserted in pulmonary artery.
      RESULTS: Patients' cardiac function and hemodynamic parameters were improved
      significantly 1 hr after administering 15 ml of MI Injection, but restored to the
      level before medication in 2-4 hrs. Administering MI injection for successive 7
      days could gradually improve patients' cardiac function and hemodynamic
      parameters after operation, and the improvement became more evident with the
      prolonging time of medication. The intubation time, intensive care unit duration
      and the time of intravenously administration of inotropic drugs in the treated
      group were significantly shorter than those in the control group (P < 0.01).
      CONCLUSION: MI could significantly improve the hemodynamics and cardiac function,
      and shorten the recovery time in children with tetralogy of Fallot after radical
      operation.

PMID- 14714358
TI  - [Effect of jiangya capsule on levels of serum nitric oxide synthase activity,
      malondialdehyde, plasma neuropeptide Y and homocysteine in patients with senile
      simple systolic hypertension].
AB  - OBJECTIVE: To observe the effect of Jiangya Capsule (JYC) on serum levels of
      nitric oxide synthase (NOS) activity and malondialdehyde (MDA), and plasma
      concentration of neuropeptide Y (NPY) and homocysteine (Hcy) in patients with
      senile simple systolic hypertension. METHODS: Randomized, double-blinded
      controlled method was adopted, the patients were divided into two groups, the
      treated group treated with JYC and the control group treated with Nimodipine.
      Changes of blood pressure, serum level of NOS and MDA, and plasma concentration
      of NPY and Hcy were observed. RESULTS: The effect of lowering blood pressure in
      the two groups were similar with insignificant difference (u = 0.24, P > 0.05).
      The total effective ratio in alleviating TCM syndrome was 90% (18/20) in the
      treated group and 60% (9/15) in the control group, comparison between them showed
      significant difference (u = 2.18, P < 0.05). After treatment, the NOS activity
      increased and MDA, NPY and Hcy levels decreased in the treated group, which
      showed significant difference as compared with those before treatment, and the
      improvement were better than those in the control group (all P < 0.05 or P <
      0.01). While in the control group after treatment, only level of MDA was lowered
      significantly (P < 0.05). CONCLUSION: JYC has good effect in treating senile
      simple systolic hypertension, it also could increase the NOS activity, lower the
      serum MDA level, obviously reduce the plasma concentration of Hcy and NPY.

PMID- 14714359
TI  - [Clinical study on effect of jiexiao oral liquid in preventing and curing virus
      induced asthma in children].
AB  - OBJECTIVE: To observe the effect and the possible mechanism of Jiexiao Oral
      Liquid (JXOL) in preventing and curing virus induced asthma in children. METHODS:
      One hundred and sixty patients of acute upper respiratory tract infection (AURTI)
      with asthma history were randomly divided into 2 groups. JXOL was given to the
      treated group within 24 hrs after occurrence of AURTI symptoms, and virazole of
      10-15 mg.kg-1.d-1 was given to the control group, the therapeutic course for both
      groups was 7 days. Changes of clinical symptoms, signs, therapeutic effect,
      pulmonary function and immuno-globulin in patients were observed. RESULTS: The
      total effective rate of the treated group was 83.8%, the clinical control rate
      was 48.8%, while those in the control group were 62.5% and 23.8% respectively,
      showing significant difference between them (P < 0.01). JXOL could obviously
      improve the indexes of forced expiratory volume in one second (FEV1) and peak
      expiratory flow (PEF), reduce the level of IgE, as compared with those before
      treatment, the difference was significant (P < 0.01 or P < 0.05); it also showed
      significant difference as compared with those in the control group after
      treatment. The changes of IgA, IgG and IgM after treatment showed insignificant
      difference. CONCLUSION: JXOL was effective in preventing and curing virus induced
      asthma in children, it also shows pulmonary function improving and immune
      regulating effects.

PMID- 14714360
TI  - [Effect of danshao granule on serum superoxide dismutase activity and
      malonyldialdehyde content in children with Henoch-Schonlein purpura nephritis].
AB  - OBJECTIVE: To explore the effect and mechanism of Danshao Granule (DSG) in
      treating Henoch-Schonlein purpura nephritis (HSPN) in children. METHODS: The 63
      patients with HSPN were randomly divided into two groups. The 32 patients in the
      treated group were treated with DSG and the 31 patients in the control group were
      treated with Tripterygium polyglycosides tablet and composite Salviae tablet. The
      therapeutic course for both groups was one month. The skin purpura, macroscopic
      hematuria, hypertension and edema subsidence time, 24 hrs urinary protein
      content, serum levels of immunoglobulins (IgA, IgG, IgM), superoxide dismutase
      (SOD) activity and malonyldialdehyde (MDA) content were observed before and after
      treatment. RESULTS: Therapeutic effect in the treated group was better than that
      in the control group in curing skin purpura and macroscopic hematuria (P < 0.05).
      The 24 hrs urinary protein content and serum levels of IgA, SOD and MDA were
      improved after treatment in both groups significantly (P < 0.01). However, the
      improvement of 24 hrs urinary protein, serum SOD and MDA in the treated group was
      more significant than that in the control group respectively (P < 0.05).
      CONCLUSION: DSG can alleviate the injury of free radicals in organism, so it is
      an ideal remedy for treatment of HSPN.

PMID- 14714361
TI  - [Clinical observation on effect of fuzheng yiliu granule on cell cycle and
      nuclear transcription factor-kappa B in tissue of esophageal-gastric carcinoma].
AB  - OBJECTIVE: To observe the effect of Fuzheng Yiliu Granule (FZYLG) on cell cycle
      and nuclear transcription factor-kappa B (NF-kappa B) in tissue of esophageal
      gastric carcinoma. METHODS: Seventy-six patients with esophageal gastric
      carcinoma were randomly divided into two groups, the FZYLG group and the control
      group. FZYLG was given to the former for 15 days. The tumor tissue in both groups
      was resected and cell cycle and apoptosis rate as well as NF-kappa B were
      determined by flowcytometry. RESULTS: Level of NF-kappa B in the treated group
      was significantly higher than that in the control group (P < 0.05). In the
      treated group, the percentage of G0/G1 stage cells were significantly increased
      and that of S stage significantly decreased (both P < 0.05). At the same time,
      obvious cell apoptosis was found in the treated group, the apoptosis rate of
      which was significantly higher than that in the control group (P < 0.01).
      CONCLUSION: FZYLG can increase the NF-kappa B expression, block the proliferation
      to promote the apoptosis of tumor cells.

PMID- 14714362
TI  - [Clinical observation on treatment of diabetic foot by integrative Chinese and
      Western Medicine].
AB  - OBJECTIVE: To observe the efficacy of integrative Chinese and western medicine
      (ICWM) in treating diabetic foot. METHODS: Sixty-three patients were randomly
      divided into the treated group (n = 33) and the control group (n = 30). Both
      groups were treated by same baseline treatment with vasodilator, anti
      agglutination agents and external treatment, to the treated group, Chinese drugs
      were given additionally according to the Syndrome Differentiation. RESULTS: In
      the treated group, the treatment showed markedly effective in 12 patients,
      effective in 18 and ineffective in 3, the total effective rate being 90.0%, while
      in the control group, the corresponding numbers were 9, 14, 7 and 76.7%,
      comparison between the two groups showed significant difference (chi 2 = 15.8, P
      < 0.05). The case number of Grade II, III and IV in the treated group reduced,
      and those recovered to Grade 0 increased, as compared with those in the control
      group, the difference was significant (P < 0.05). Patients with healing of
      ulcerative wound and fresh wound granulation in the treated group, as compared
      with those in the control group, the difference was significant (P < 0.05).
      Levels of fasting blood glucose and blood glucose 2 hrs after meal were all
      improved in both groups, which showed significant difference as compared with
      those before treatment (P < 0.05). CONCLUSION: The efficacy of ICWM treatment in
      treating diabetic foot was better than the treatment of western medicine alone.

PMID- 14714363
TI  - [Possible mechanism of electroacupuncture preconditioning for hypoxia/ischemic
      brain injury protection effect in neonatal rats].
AB  - OBJECTIVE: To explore the possible mechanism of electroacupuncture
      preconditioning (EAPC) and combined with ATP-sensitive potassium channel (KATP)
      blocker preconditioning for hypoxia/ischemic brain injury protection by observing
      the changes of the immediate genes (c-fos and c-jun protein content) in brain at
      the early stage after cerebral hypoxia/ischemic injury, and the effect of EAPC on
      these changes. METHODS: Integrated density (ID) of c-fos and c-jun expression was
      measured by Western blot and computerized image processing. RESULTS:
      Hypoxia/ischemia could induce c-fos and c-jun protein in both cerebral cortex and
      hippocampus simultaneously, with the peak appearing 2-4 hrs later, and the
      expression in hyppocampus was higher than that in cortex. EAPC could lower KATP
      blocker induced permanent high expression in hyppocampus. CONCLUSION: The effect
      of EAPC preconditioning in antagonizing cerebral hypoxia/ischemic injury may be
      related with its action in activating KATP, inhibiting the neuron apoptosis
      induced by the immediate genes at early stage of injury.

PMID- 14714364
TI  - [On English translation of some terms concerning characteristics of Chinese
      herbal medicine].

PMID- 14714365
TI  - [Effect of sodium ferulate on activation of extracellular signal regulated kinase
      after cerebral ischemia/reperfusion injury in rats].
AB  - OBJECTIVE: To study the activation of extracellular signal regulated kinase (ERK)
      after focal cerebral ischemia/reperfusion in rats and the effect of sodium
      ferulate (SF) on it. METHODS: Forty-five male adult SD rats were randomly divided
      into 3 groups, the sham-operated group, the control group and the SF group. The
      model of middle cerebral artery occlusion (MCAO) was established by thread
      ligation method, and in the ischemic phase, to rats in the sham-operated and the
      control group 4 ml of normal saline was intraperitoneally injected, and to rats
      in the SF group, 100 mg/kg of SF dissolved in 4 ml of normal saline was injected.
      The rats were decapitated at 2 hrs, 6 hrs, 12 hrs, 24 hrs and 72 hrs after
      reperfusion, 3 rats of every group at each time point, and rats brains were taken
      for immunohistochemistry and histopathological examination. RESULTS:
      Histopathological examination showed that the cerebral ischemic damage in the SF
      group was significantly milder than that in the control group at 2 hrs after
      reperfusion. The cerebral ischemia induced ERK activation reached the peak at 6
      hrs and maintained to 72 hrs after reperfusion. As compared with the control
      group, the ERK activation in the SF group was significantly enhanced with
      increased positive immune reacted cells (P < 0.01). CONCLUSION: Cerebral
      ischemia/reperfusion could induce the activation of ERK in the ischemic brain
      cells, intervention of SF could enhance the activation and alleviate the ischemic
      injury in cerebral cortex.

PMID- 14714366
TI  - [Experimental study on the anti-liver fibrosis effect of guzhang tablet in rats].
AB  - OBJECTIVE: To observe the anti-liver-fibrosis effect of Guzhang Tablet (GZT) and
      to explore its mechanism. METHODS: Fifty female rats, weighing 200-220 g were
      randomly divided into the blank control group, the model group, the small dosage
      GZT group, the large dosage GZT group and the Biejiajian Pill (BJJP) group, 10
      rats in each group. The changes of related serum enzymes, liver-fibrosis marker,
      oxygen free radical and liver tissue pathology were observed after 8 weeks of
      treatment. RESULTS: (1) Compared with the model group, the serum levels of
      alanine transaminase (ALT), aspartate aminotransferase (AST),
      glutamyltranspetidase (GGT), alkaline phosphatase (AKP) were improved in the GZT
      groups, better effect was got in the large dosage GZT group. (2) Compared with
      the blank control group, GZT showed no effect on serum total protein (TP) but
      with raising albumin (ALB) effect. (3) Compared with blank control group, the
      levels of hyaluronidase (HA), laminin (LN), collagen type IV (IV-C) and
      procollagen type III (PC III) in both GZT groups were lower, especially in the
      large dosage GZT group. (4) Small and large dosage of GZT showed effect in
      reducing malonyldialdehyde (MDA), Glutathione-peroxidose(GSH-Px) and nitric oxide
      (NO) content, but the effect on increasing superoxide dismutase (SOD) similar to
      that of BJJP with no significant different. (5) GZT, both small and large dosage,
      had obvious anti-liver fibrosis action, which was superior to that of BJJP.
      CONCLUSION: In the genetic and developing processes of liver fibrosis in rats,
      GZT could protect the liver cells, inhibit the synthesis and reduce the content
      of collagens, the mechanism might be related with its action in antagonizing
      peroxidation injury, indicating that GZT could effectively prevent liver fibrosis
      formation.

PMID- 14714367
TI  - [Effect of wolfberry fruit and epimedium on DNA synthesis of the aging-youth 2BS
      fusion cells].
AB  - OBJECTIVE: To study the effect of water extracts of Wolfberry fruit (WB) and
      Epimedium (EM) on DNA synthesis of the aging-youth 2BS fusion cells. METHODS:
      Human embryonic lung diploid fibroblasts 2BS national standard strain, were used
      as an aging model. Cell denucleation and cell fusion techniques were applied to
      observe the effect of WB and EM on DNA synthesis of 2BS fusion cells. RESULTS: In
      the 0.025 (V/V) WB or EM water extract containing media, 2BS cells could be
      continuously cultured for 61.0 +/- 2.9 passages and 56.0 +/- 2.6 passages
      respectively, while in the control group it was only 49.0 +/- 2.6 passages (P <
      0.01). After treatment with WB and EM separately for 2 hrs, the aging 2BS cells
      were denucleated and fused with young 2BS cells. The [3H]TdR incorporation
      percentage in these treated cells was significantly higher than that in the
      untreated control cells (P < 0.01). CONCLUSION: Both WB and EM can accelerate the
      DNA synthesis rate of the aging youth 2BS fusion cells and prolong the life span
      of 2BS cells.

PMID- 14714368
TI  - [Clinical observation on treatment of 107 patients with fatty liver by jinchan
      shugan powder].

PMID- 14714369
TI  - [Application of arsenic trioxide in comprehensive therapy of liver carcinoma].

PMID- 14714371
TI  - [Some problems of animal model establishment of coronary heart disease with xin
      yang deficiency].

PMID- 14714370
TI  - [Clinical observation on treatment of scicca syndrome complicated with damage of
      blood system by TCM].

PMID- 14714372
TI  - [Progress of experimental research on prevention and treatment of osteoporosis by
      traditional Chinese medicine].

PMID- 14714373
TI  - [Analysis of application and utilization of anti-tumor drugs and its assistant
      patent Chinese drugs].

PMID- 14714374
TI  - [Summary of conference on homonization of traditional Chinese medicine and modern
      medicine held by WHO for the 2nd time].

PMID- 14714375
TI  - Experimental and computational investigations of the properties of fluorinated
      single-walled carbon nanotubes.
AB  - Fluorination of single-walled carbon nanotubes by reaction with elemental
      fluorine at elevated temperatures provides fluorinated single-walled carbon
      nanotubes (F-SWNT), which have the highest degree of functionalization (up to F/C
      = 1/2) of any derivatized carbon-nanotube material reported to date. Also, F
      SWNTs have received more scrutiny than any other functionalized carbon nanotubes.
      This Minireview covers experimental and computational investigations of F-SWNTs
      with a focus on the nature and the strength of the C-F linkage.

PMID- 14714376
TI  - Trends in microfluidics with complex fluids.
AB  - The rapid developments in biotechnology create a great demand for fluid handling
      systems on the nano- and picoliter scale. The characterization of minute
      quantities of DNA or protein samples requires highly integrated, automated, and
      miniaturized "total analysis systems" (mu-TAS). The small scales necessitate new
      concepts for devices both from a technological and from a fundamental physical
      point of view. Here, we describe recent trends in both areas. New technologies
      include soft lithography, chemical, and topographical structuring of surfaces in
      order to define pathways for liquids, as well as electro-wetting for manipulation
      purposes. Fundamentally, the interplay between geometric confinement and the size
      of biological macromolecules gives rise to complex dynamic behavior. The
      combination of both fluorescence imaging and scattering techniques allows for
      detailed insight into the dynamics of individual molecules and into their self
      assembly into supramolecular aggregates.

PMID- 14714377
TI  - Dynamics of photoinduced electron-transfer processes in fullerene-based dyads:
      effects of varying the donor strength.
AB  - Two classes of fullerene-based donor-bridge-acceptor (D-B-A) systems containing
      donors of varying oxidation potentials have been synthesized. These systems
      include fullerenes linked to heteroaromatic donor groups
      (phenothiazine/phenoxazine) as well as substituted anilines (p-anisidine/p
      toluidine). In contrast to the model compound, an efficient intramolecular
      electron transfer is observed from the fullerene singlet excited state in polar
      solvents. An increase in the rate constant and quantum yield of charge separation
      (kcs and phi cs) has been observed for both classes of dyads, with decrease in
      the oxidation potentials of the donor groups. This observation indicates that the
      rates of the forward electron transfer fall in the normal region of the Marcus
      curve. The long-lived charge separation enabled the characterization of electron
      transfer products, namely, the radical cation of the donor and radical anion of
      the pyrrolidinofullerene, by using nanosecond transient absorption spectroscopy.
      The small reorganization energy (lambda) of C60 coupled with large negative free
      energy changes (-delta G degree) for the back electron transfer places the back
      electron process in the inverted region of Marcus curve, thereby stabilizing the
      electron transfer products.

PMID- 14714378
TI  - The low-lying excited states of 2,2'-bithiophene: a theoretical analysis.
AB  - The low-energy region of the singlet-->singlet, singlet-->triplet, and triplet-
      >triplet electronic spectra of 2,2'-bithiophene are studied using
      multiconfigurational second-order perturbation theory (CASPT2) and extended
      atomic natural orbitals (ANO) basis sets. The computed vertical, adiabatic, and
      emission transition energies are in agreement with the available experimental
      data. The two lowest singlet excited states, 1(1)Bu and 2(1)Bu, are computed to
      be degenerate, a novel feature of the system to be borne in mind during the
      rationalization of its photophysics. As regards the observed high triplet quantum
      yield of the molecule, it is concluded that the triplet states 2(3)Ag and 2(3)Bu,
      separated about 0.4 eV from the two lowest singlet excited states, can be
      populated by intersystem crossing from nonplanar singlet states.

PMID- 14714380
TI  - Generation of iron atoms in the gas phase by microwave-induced plasma afterglows.
AB  - A fast-flow reactor technique is described by which Fe atoms can be produced in
      the gas phase in the afterglow of microwave-induced plasmas in hydrogen/argon and
      hydrogen/helium mixtures. When the iron salt FeCl3(s) was brought into the gas
      phase by thermal sublimation at temperatures between 360 and 405 K, it was partly
      converted to Fe atoms by reaction of the gaseous compounds FexCl3x(g) with
      hydrogen atoms. The Fe atoms were detected by atomic absorption spectroscopy
      (AAS). It was shown that sublimation of the salt is the rate-determining step of
      the overall plasma-afterglow atomisation process. Experimental conditions for the
      generation of Fe atoms suited to kinetic studies start at a temperature of 303 K.
      In the downstream region the concentration of Fe atoms decays due to diffusion to
      the reactor wall. Binary diffusion coefficients DFe/Ar and DFe/He of 231.5 +/-
      6.6 and 370.0 +/- 15.5 cm2 s-1 Torr at 303 K, respectively, were determined.

PMID- 14714379
TI  - In-plane structures of synthetic oligolactose lipid monolayers--impact of
      saccharide chain length.
AB  - Grazing incidence X-ray diffraction (GIXD) was used to investigate the in-plane
      structure of monolayers of synthetic glycolipids with oligolactose head groups
      (Lac N, with N = number of lactose units) at the air/water interface. The Lac 1
      monolayer exhibits three sharp diffraction peaks. One peak can be deconvoluted
      into two diffraction peaks, which suggests that alkyl chains in the monolayer
      form an orthorhombic lattice. On the other hand, the other two peaks are related
      to bulk crystalline materials residing at the interface. Another weak peak from
      the head group correlation, either in a monolayer or in bulk crystals, can also
      be observed in some experiments. The scattering patterns of the Lac 2 monolayer
      indicate that the alkyl chains order in an orthorhombic lattice, where a shift in
      the hydrophilic/hydrophobic balance seems to fluidize the film. Alkyl chains in
      the Lac 3 monolayer also seem to assume an orthorhombic lattice; however, a weak
      diffraction peak from the correlation between trilactose head groups can also be
      observed. The estimated lattice dimensions are compared systematically to those
      of bulk dispersions, as well as to the viscoelastic properties of the monolayer.
      The obtained results strongly suggest that the in-plane structure of synthetic
      glycolipid monolayers can provide a well-defined basis to understand the impact
      of the chemical structure on the cooperativity and function of the glycocalix of
      cellular surfaces.

PMID- 14714381
TI  - Co-conformational distribution of nanosized [2]catenanes determined by pulse EPR
      measurements.
AB  - The co-conformational ensembles of three differently sized [2]catenanes were
      studied by measuring pair correlation functions corresponding to the separation
      of nitroxide spin labels--one attached to each of the two macrocycles--with the
      double electron-electron resonance (DEER) experiment. A geometric model for the
      [2]catenanes was derived that approximates the macrocycles by circles and takes
      into account the topological constraint. Comparison of the experimental to the
      theoretically predicted pair correlation functions gives insight into the co
      conformational distribution and the size of the macrocycles. It was found that
      the macrocycles of the medium- and large-sized catenanes in chloroform are close
      to fully expanded, while they are partially collapsed in glassy o-terphenyl. For
      the small-sized catenane, moderate interaction between the unsaturated sections
      of the macrocycles in chloroform is indicated by a slight over-representation of
      short label-to-label separations in the pair correlation function.

PMID- 14714382
TI  - Single-walled carbon nanotube based molecular switch tunnel junctions.
AB  - This article describes two-terminal molecular switch tunnel junctions (MSTJs)
      which incorporate a semiconducting, single-walled carbon nanotube (SWNT) as the
      bottom electrode. The nanotube interacts noncovalently with a monolayer of
      bistable, nondegenerate [2]catenane tetracations, self-organized by their
      supporting amphiphilic dimyristoylphosphatidyl anions which shield the
      mechanically switchable tetracations from a two-micrometer wide metallic top
      electrode. The resulting 0.002 micron 2 area tunnel junction addresses a
      nanometer wide row of approximately 2000 molecules. Active and remnant current
      voltage measurements demonstrated that these devices can be reconfigurably
      switched and repeatedly cycled between high and low current states under ambient
      conditions. Control compounds, including a degenerate [2]catenane, were explored
      in support of the mechanical origin of the switching signature. These SWNT-based
      MSTJs operate like previously reported silicon-based MSTJs, but differently from
      similar devices incorporating bottom metal electrodes. The relevance of these
      results with respect to the choice of electrode materials for molecular
      electronics devices is discussed.

PMID- 14714383
TI  - Electron attachment to "naked" and microsolvated nucleotide anions: detection of
      long-lived dianions.

PMID- 14714384
TI  - A topological analysis of the electron density in anion-pi interactions.

PMID- 14714385
TI  - Trapping electrochemical oscillations between self-organized potential walls.

PMID- 14714386
TI  - Biointerfacing polyelectrolyte microcapsules.

PMID- 14714387
TI  - Self-organization of an L-ether-amide phospholipid in large two-dimensional
      chiral crystals.

PMID- 14714388
TI  - One-bond 15N-13C' nuclear spin-spin coupling in N-methylacetamide: a model for
      hydrogen-bonded peptides.

PMID- 14714389
TI  - Noncontact surface force microscopy of protein molecules.

PMID- 14714390
TI  - Wiring electrons of cytochrome c with silver nanoparticles in layered films.

PMID- 14714391
TI  - Covalent immobilization of single proteins on mica for molecular recognition
      force microscopy.

PMID- 14714392
TI  - Probing nanomagnets' interactions inside colloidal superparamagnetic composites:
      aerosol versus surface template methods.

PMID- 14714393
TI  - "In vivo" depletion of macrophages by liposome-mediated "suicide".

PMID- 14714394
TI  - Trafficking of liposomal antigens to the trans-Golgi complex in macrophages.

PMID- 14714395
TI  - Oil-in-water liposomal emulsions for vaccine delivery.

PMID- 14714396
TI  - Synthetic peptide-based highly immunogenic liposomal constructs.

PMID- 14714397
TI  - Influenza virosomes in vaccine development.
AB  - Influenza virosomes can be regarded as unilamellar liposomes carrying the spike
      proteins of influenza virus on their surface. Vaccination with influenza
      virosomes elicits high titers of influenza-specific antibodies, indicating that
      HA (and NA) reconstituted into a membranous environment exhibit strong
      immunogenicity. Moreover, virosomes can be used as presentation systems for
      unrelated antigens bound to the virosome surface. Because of their intrinsic
      adjuvant activity, virosomes support antibody formation and induction of T-helper
      cell responses against such surface-associated antigens. Provided that the
      fusogenic properties of the reconstituted HA are retained, virosomes can also be
      used to elicit cytotoxic T-cell responses against encapsulated antigens. Vaccines
      capable of activating the cellular branch of the immune response can be very
      important for protection against acute virus infections, especially for viruses
      with rapidly changing envelope glycoproteins like HIV and influenza virus.
      Moreover, virosomes can suit as powerful carriers in the development of
      prophylactic and immunotherapeutic strategies against cancer and premalignant
      disease. The use of virosomes as commercial influenza vaccine and as commercial
      adjuvant for a hepatitis A vaccine demonstrates that production of virosomes on
      an industrial scale is feasible, both technically and economically. The
      industrial production procedure currently followed has not been designed to
      retain the functional properties of HA. In fact, several steps in the procedure
      are probably incompatible with retention of fusion activity. As mentioned
      previously the fusogenic properties of virosomes are important for CTL activation
      and might also play a role in the induction of T-helper cell and antibody
      responses. Therefore, a number of key adaptations in the virosome production
      protocol will be necessary. Thus improved, virosomes are very attractive devices
      for the development of highly efficacious vaccines against a range of antigens.

PMID- 14714398
TI  - Liposomal cytokines and liposomes targeted to costimulatory molecules as
      adjuvants for human immunodeficiency virus subunit vaccines.

PMID- 14714399
TI  - Liposomes targeted to Fc receptors for antigen presentation by dendritic cells in
      vitro and in vivo.

PMID- 14714400
TI  - Liposomes composed of reconstituted membranes for induction of tumor-specific
      immunity.

PMID- 14714401
TI  - pH-sensitive liposomes as adjuvants for peptide antigens.

PMID- 14714402
TI  - The interaction of liposomes with the complement system: in vitro and in vivo
      assays.

PMID- 14714403
TI  - Archaeobacterial ether lipid liposomes as vaccine adjuvants.

PMID- 14714404
TI  - Magnetoliposomes as contrast agents.

PMID- 14714405
TI  - Liposomes in ultrasound and gamma scintigraphic imaging.

PMID- 14714406
TI  - Visualization of the retinal and choroidal microvasculature by fluorescent
      liposomes.

PMID- 14714407
TI  - Radiolabeling of liposomes for scintigraphic imaging.

PMID- 14714408
TI  - Preparation of a liposomal reagent and its use in an immunoassay for albumin.

PMID- 14714409
TI  - Liposome immunoassays using phospholipase C or alkaline phosphatase.

PMID- 14714410
TI  - Lipoplex assembly visualized by atomic force microscopy.

PMID- 14714411
TI  - Biophysical characterization of cationic liposome-DNA complexes and their
      interaction with cells.

PMID- 14714412
TI  - Calorimetry of cationic liposome-DNA complex and intracellular visualization of
      the complexes.

PMID- 14714414
TI  - Transferrin-lipoplexes with protamine-condensed DNA for serum-resistant gene
      delivery.

PMID- 14714413
TI  - Cationic liposome-protamine-DNA complexes for gene delivery.

PMID- 14714415
TI  - DNA complexes with reducible cationic lipid for gene transfer.

PMID- 14714416
TI  - Gene delivery by cationic liposome-DNA complexes containing transferrin or serum
      albumin.

PMID- 14714417
TI  - Glycosylated cationic liposomes for carbohydrate receptor-mediated gene transfer.

PMID- 14714418
TI  - Asialofetuin liposomes for receptor-mediated gene transfer into hepatic cells.

PMID- 14714419
TI  - Fusogenic polymer-modified liposomes for the delivery of genes and charged
      fluorophores.

PMID- 14714420
TI  - Liposome-mediated gene delivery: dependence on lipid structure, glycolipid
      mediated targeting, and immunological properties.

PMID- 14714421
TI  - Phage DNA transfer into liposomes.

PMID- 14714422
TI  - The hemagglutinating virus of Japan-liposome method for gene delivery.

PMID- 14714423
TI  - Enhancement of retroviral transduction by cationic liposomes.

PMID- 14714424
TI  - Gene targeting in vivo with pegylated immunoliposomes.

PMID- 14714425
TI  - Liposome-mediated cytokine gene delivery to human tumor xenografts.

PMID- 14714426
TI  - Cationic liposome-mediated gene delivery in vivo.

PMID- 14714429
TI  - Serodiagnosis of flaviviral infections and vaccinations in humans.

PMID- 14714431
TI  - Japanese encephalitis.

PMID- 14714430
TI  - Molecular amplification assays for the detection of flaviviruses.
AB  - Over the past 10 years, a number of molecular amplification assays have been
      developed for the detection of flaviviruses. Most of these assays utilize the
      reverse transcriptase-polymerase chain reaction (RT-PCR) as the amplification
      format with detection by either agarose gel electrophoresis and ethidium bromide
      staining or hybridization with molecular probes. Recently, a modification of the
      standard RT-PCR using fluorescent-labeled oligonucleotide probes for detection
      (TaqMan) has been described. As a result, several assays for detecting
      flaviviruses have been developed using this approach. In addition, another
      amplification format, nucleic acid sequence based amplification (NASBA), has been
      developed and utilized for the detection of several flaviviruses. The various
      assay formats will be described and their utility discussed.

PMID- 14714432
TI  - Epidemiology of St. Louis encephalitis virus.

PMID- 14714433
TI  - West Nile virus: epidemiology and ecology in North America.

PMID- 14714434
TI  - Dengue epidemiology: virus epidemiology, ecology, and emergence.

PMID- 14714435
TI  - Epidemiology and ecology of yellow fever virus.

PMID- 14714436
TI  - Tick-borne flaviviruses.
AB  - Tick-borne encephalitis (TBE), one of the most dangerous neuroinfections in
      Europe and Asia, is caused by tick-borne encephalitis virus (TBEV) and currently
      involves approximately 11,000 human cases annually, mostly in Russia. This
      chapter describes the main problems associated with the epidemiology, ecology,
      pathogenesis, and control of this disease. We have attempted to review the
      factors that influence the incidence and distribution of TBE, and to discuss
      possible reasons for the different clinical manifestations including most
      commonly observed asymptomatic infections, fever forms, acute encephalitis, and
      the less frequently registered biphasic milk fever and chronic encephalitis.
      Epidemiologic data concerning the other tick-borne flaviviruses, namely Louping
      ill virus, Langat virus, and Powassan virus that also produce encephalitis on a
      smaller scale, are also presented. Here we describe the history and current
      epidemiological role of Omsk hemorrhagic fever virus and Kyasanur forest disease
      virus, two viruses that are genetically closely related to TBEV, but produce
      hemorrhagic fever instead of encephalitis, and provide possible explanations for
      these differences. The other viruses in the tick-borne flavivirus group are also
      included despite the fact that they do not play an essential epidemiologic role
      in humans. This chapter contains a brief history of vaccination against TBE
      including the trials with live attenuated vaccine and reviews the modern trends
      in development of vaccine virus strains.

PMID- 14714437
TI  - Epidemiology of other arthropod-borne flaviviruses infecting humans.

PMID- 14714438
TI  - Formalin-inactivated whole virus and recombinant subunit flavivirus vaccines.
AB  - The Flaviviridae is a family of arthropod-borne, enveloped, RNA viruses that
      contain important human pathogens such as yellow fever (YF), Japanese
      encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), and the dengue
      (DEN) viruses. Vaccination is the most effective means of disease prevention for
      these viral infections. A live-attenuated vaccine for YF, and inactivated
      vaccines for JE and TBE have significantly reduced the incidence of disease for
      these viruses, while licensed vaccines for DEN and WN are still lacking despite a
      significant disease burden associated with these infections. This review focuses
      on inactivated and recombinant subunit vaccines (non-replicating protein
      vaccines) in various stages of laboratory development and human testing. A
      purified, inactivated vaccine (PIV) candidate for DEN will soon be evaluated in a
      phase 1 clinical trial, and a second-generation JE PIV produced using similar
      technology has advanced to phase 2/3 trials. The inactivated TBE vaccine used
      successfully in Europe for almost 30 years continues to be improved by additional
      purification, new stabilizers, an adjuvant, and better immunization schedules.
      The recent development of an inactivated WN vaccine for domestic animals
      demonstrates the possibility of producing a similar vaccine for human use.
      Advances in flavivirus gene expression technology have led to the production of
      several recombinant subunit antigen vaccine candidates in a variety of expression
      systems. Some of these vaccines have shown sufficient promise in animal models to
      be considered as candidates for evaluation in clinical trials. Feasibility of non
      replicating flavivirus vaccines has been clearly demonstrated and further
      development is now warranted.

PMID- 14714439
TI  - Empirically derived live-attenuated vaccines against dengue and Japanese
      encephalitis.

PMID- 14714440
TI  - DNA vaccines for flaviviruses.

PMID- 14714441
TI  - Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne
      encephalitis, and Japanese encephalitis.
AB  - Many arthropod-borne flaviviruses are important human pathogens responsible for
      diverse illnesses, including YF, JE, TBE, and dengue. Live, attenuated vaccines
      have afforded the most effective and economical means of prevention and control,
      as illustrated by YF 17D and JE SA14-14-2 vaccines. Recent advances in
      recombinant DNA technology have made it possible to explore a novel approach for
      developing live attenuated flavivirus vaccines against other flaviviruses. Full
      length cDNA clones allow construction of infectious virus bearing attenuating
      mutations or deletions incorporated in the viral genome. It is also possible to
      create chimeric flaviviruses in which the structural protein genes for the target
      antigens of a flavivirus are replaced by the corresponding genes of another
      flavivirus. By combining these molecular techniques, the DNA sequences of DEN4
      strain 814669, DEN2 PDK-53 candidate vaccine and YF 17D vaccine have been used as
      the genetic backbone to construct chimeric flaviviruses with the required
      attenuation phenotype and expression of the target antigens. Encouraging results
      from preclinical and clinical studies have shown that several chimeric flavivirus
      vaccines have the safety profile and satisfactory immunogenicity and protective
      efficacy to warrant further evaluation in humans. The chimeric flavivirus
      strategy has led to the rapid development of novel live-attenuated vaccines
      against dengue, TBE, JE, and West Nile viruses.

PMID- 14714442
TI  - Prospects for antiviral therapy.

PMID- 14714443
TI  - Gender-specific health care for transgendered individuals.

PMID- 14714444
TI  - When the doctor needs a doctor.

PMID- 14714445
TI  - Bridging the language gap: provider duty and options for providing linguistically
      appropriate health care.

PMID- 14714446
TI  - Gender differences in chronic pain in a treatment-seeking population.
AB  - OBJECTIVE: To compare pain characteristics, disability, and comorbid
      psychological distress between genders in a treatment-seeking sample of patients
      with chronic pain. METHODS: Consecutive patients with chronic pain were evaluated
      and assigned a pain diagnosis. Gender differences were compared on responses to
      questions about pain symptoms, associated disability, and psychological distress.
      RESULTS: The pain sample (N = 716) was predominately female (63%). Pain
      locations, diagnoses, and trigger factors were similar in male and female
      patients. Male patients reported a greater mean pain severity (7.16 males vs 6.82
      females; P = 0.05), greater pain constancy (41.2% vs 26.7%; P < 0.001), and more
      days per week with pain (6.37 vs 5.87; P < 0.001). In addition, males reported
      higher levels of disability, with reduced activity more than 3 days per week in
      70.2% of males and 56.0% of females, and complete disability more than 3 days per
      week in 55.9% of males and 37.3% of females (P < 0.001). Quality of life measures
      were additionally reduced for both physical and psychological categories in men
      versus women (P = 0.05 to < 0.01). CONCLUSIONS: There are important gender
      differences in treatment-seeking patients with chronic pain. Males report higher
      levels of pain and disability, with reduced physical and psychological quality of
      life, as compared to females. These differences in treatment-seeking patients may
      reflect gender differences in treatment-seeking behavior.

PMID- 14714447
TI  - A review of the overactive bladder in women and men.
AB  - Urinary incontinence is a major medical problem that affects people worldwide.
      More than 17 million people in the United States are affected by the disorder,
      with billions of dollars in annual costs. The overactive bladder is a major cause
      of incontinence. The symptoms of frequent urination, pain, and leakage of urine
      range in severity and debilitation. Overactive bladder produces significant
      social and physical ramifications that if left untreated result in a dismal
      quality of life. Newer medications that have been developed allow simple oral
      treatment. Most patients can now be treated successfully and compassionately.

PMID- 14714448
TI  - The influence of gender on patient satisfaction.
AB  - OBJECTIVE: To investigate the influence of gender on patient satisfaction with
      hospitalization care. METHODS: A random-selection, cross-sectional study was
      conducted. Data were collected by telephone interviews over a 2-year period
      utilizing a 16-item survey. Inclusion criteria were hospital admission between
      July 1, 1999 and July 1, 2001, age greater than 18 years, and the ability to
      speak on the telephone. Exclusion criteria were an admission for an obstetric
      purpose, physical rehabilitation, or psychiatric illness, or the inability to be
      reached by a telephone call. Logistic regression was used to compare gender with
      the responses for each of the 16 questions, while controlling for three
      confounders (age, race, and insurance status). RESULTS: 5857 patients were
      surveyed. Compared to men, women were significantly younger, had a higher
      percentage of African Americans, and more had Medicaid insurance (P < 0.05).
      Using multivariate analysis, women expressed significantly less satisfaction
      compared to men on four of the six questions related to nursing care, on three of
      the three questions related to entire staff care, on three of the three questions
      related to overall satisfaction, and on one of the two questions related to
      communication (P < 0.05). There was no difference in satisfaction between the
      genders for the two questions regarding physician are.

PMID- 14714449
TI  - Sequence-based polymorphisms in members of the apoptosis Bcl-2 gene family and
      their association with hematocrit level.
AB  - OBJECTIVE: The Bcl-2 family mediates erythropoietin-dependent survival of
      erythroid progenitor cells and regulates erythropoiesis. We assessed for any
      association between Bcl-2 family nucleotide variation and hematocrit (HCT) in
      healthy blood donors. METHODS: We screened Bcl-w, Bcl-x, and Bax (members of Bcl
      2 family) using polymerase chain reaction and singlestrand conformation
      polymorphism analysis. One polymorphism each was found in Bax and Bcl-w. Using
      these markers, we genotyped the 100 males and 100 females with the highest or
      lowest HCT in a population of 819 healthy people in Iowa. A comparison of the
      allelic frequencies and distribution of each polymorphism was made in males
      versus females, individuals with low versus high HCT, and other subgroups.
      RESULTS: One sequence-based polymorphism was found in Bax and Bcl-w having three
      and two alleles, respectively. No polymorphism was found for Bcl-x. The Bax
      polymorphism is caused by variation in nucleotide A repeat number (19, 25, 27) at
      position 360 in 5'-region of Bax. The Bcl-w polymorphism is a G to A transition
      at 123. The allelic frequencies of Bax polymorphism were significantly different
      between males and females (P = 0.004). There were no significant associations for
      Bcl-w polymorphism by gender or HCT level (P > 0.05). CONCLUSIONS: Polymorphism
      in the 5'-region of Bax was associated with gender-based HCT differences. This is
      theoretically due to gender-based hormonal effects on gene transcription mediated
      by the different polymorphisms.

PMID- 14714450
TI  - [Genetic control of spermatogenesis and sex determination in mammals].
AB  - The material was analyzed on the main problems of genetics of mammalian
      spermatogenesis, sex determination, its reversion and other defects from the
      standpoint of current cytological and molecular-genetic concepts of functional
      activity of the parental genomes after fertilization and behavior of their
      chromosomes at the early embroyonic stages. On the basis of this analysis, a
      hypothesis has been proposed, which explains a high percentage (50% or more) of
      early embryonic mortality in placental mammals under the conditions of natural
      and extracorporeal fertilization, as well as regular appearance of defects in the
      course of natural sex determination, including the appearance of representatives
      of both sex minorities. We do not make pretense to comprehensive and deep
      analysis of male gametogenesis and sex determination in mammals.

PMID- 14714451
TI  - [Retina of vertebrates: an internal cell reserve for regeneration].
AB  - The recent data were summarized concerning the presence in the retina of fish,
      amphibians and birds of additional sources of growth and regeneration,
      alternative to the already known sources, such as growth zone of eye, pigment
      epithelium, and cells--precursors of rods, and which are localized in the inner
      nuclear layer of retina. These sources are represented by as yet not finally
      identified oval small cells and cells of Muller glia. Both types of cells are
      capable of proliferating and producing precursors for various differentiated
      cells, including photoreceptors or their additional precursors. The current
      immunochemistry data are provided, which were obtained using markers of
      proliferation, proneural phenotype, and specific cell differentiation in the
      growing retina and in the retina after various damages. The regulatory mechanisms
      and methods of the stimulation of proliferation of the cells, which are sources
      of increase in the number and restoration of photoreceptors, interneurons, and
      glial cells of vertebrate retina, are discussed.

PMID- 14714452
TI  - [Role of auxin in induction of polarity in zygotes of Fucus vesiculosus L].
AB  - We studied the effects of auxin (indolyl-3 acetic acid) on formation of the
      primary polarity axis in zygotes of the brown algae Fucus vesiculosus. Within the
      first 2.5 h after fertilization, the zygotes release this phytohormone in the
      environment. The treatment of developing zygotes with the inhibitor of indolyl-3
      acetic acid transport from the cell triiodobenzoic acid at 5 mg/l arrests the
      auxin secretion and leads to its accumulation in the cells. This causes a
      significant delay in zygote polarization. The treatment of zygotes with the
      exogenous indolyl-3-acetic acid at 1 mg/l stimulates cell polarization and
      formation of a rhizoid process. When auxin was added to the medium with
      triiodobenzoic acid, the inhibitory effect of the latter was fully relieved. It
      has been proposed that the content of indolyl-3-acetic acid in the environment is
      a key factor in the induction of polarity of the F. vesiculosus zygotes.

PMID- 14714453
TI  - [An experimental study on the formation of anterior-posterior polarity in the
      early development of the marine hydroid Dynamena pumila].
AB  - Elements of evolutionarily initial morphogenesis providing for the formation of
      main body axes could have been preserved in embryogenesis of lower Metazoa
      animals, Cnidaria. However, the information on the morphological bases of axes
      formation in their normal development is not yet complete. When studying the
      normal development of Dynamena pumila (Hydrozoa, Thecaphora, Sertulariidae), it
      has been proposed that the region, where the embryonic ectoblast remained
      unclosed for the longest time, determines the position of the posterior pole of
      the larval anteroposterior axis. In the experiments, the formation of closed
      ectoblast in an arbitrarily chosen region of the embryonic surface was delayed
      artificially, for example, by incisions. The fate of this region was traced with
      the help of a mark consisting of carmine particles. It was shown that the
      posterior pole did differentiate near the region of surface, which was the last
      to epithelize and redetermination of the anteroposterior axis orientation was
      only possible before the formation of closed ectoblast in the normal development.
      The morphogeneses involved in the formation of anteroposterior axis and its poles
      in Dynamena embryos were reconstructed by means of observations over the
      displacement of mark particles. It was shown that the establishment of this axis
      and appearance of morphological differences between the anterior and posterior
      planula poles are morphogenetic consequences of the closed ectoblast formation.
      The region, in which the closure of ectoblast is delayed, is a functional analog
      of the blastopore of higher Metazoa.

PMID- 14714454
TI  - [Statistical and frequency-amplitude characteristics of ultra-weak emissions of
      loach eggs and embryos under normal conditions and on their optic interactions.
      II. Changes in characteristics of ultra-weak emissions upon optic interaction of
      groups of embryos of different ages. ].
AB  - We compared the characteristics of ultraweak emissions from groups of loach
      embryos of different ages in the presence or absence of optic interaction. The
      percentage of zero values of emission gradually increased during the first hour
      of optic interaction. The number and height of rare big pulses estimated by the
      value of kurtosis increased in parallel. In addition, the correlation between the
      Fourier spectra of optically interacting samples decreased at a higher rate than
      in the absence of optical contact. Just after the 1-hour optic interaction was
      terminated, the number of high pulses decreased in a younger interacting group
      and increased in the older one and the farther away the partner groups were in
      developmental stages, the more pronounced these differences were. Measurements of
      the Fourier spectra after long-term (12-22-hour) optic interactions have shown
      that an "exchange" of autocorrelation characteristics of the spectra took place
      among the samples: the sums of autocorrelation coefficients were inverted in the
      vast majority of cases, often with an "overshoot" or, at least, were smoothed
      over with reference to the control samples. We conclude that the previously
      described effects of optic interactions between groups of loach embryos of
      different ages could be due to changes in the frequency spectra of their
      ultraweak emissions.

PMID- 14714455
TI  - [Effect of neonatal influences on pain and audiogenic sensitivity and the content
      of monoamines in the adult rat brain].
AB  - In adult Wistar, KM, and Wag/Rij rats, the threshold of pain sensitivity (tail
      flick test) and degree of spasm attack in response to a strong sound were
      estimated after neonatal administration of Semaks (analog of ACTG4-10 fragment)
      or after placebo (administration of saline for the control of the effect of
      neonatal pain stimulation). These neonatal influences did no affect the rates of
      sensorimotor maturation at an early age (Fox tests), i.e., did not affect
      directly the physiological activity of rat pups at the age of up to 21 days. In
      all control rats injected with saline (pain stimulation), the latent periods of
      audiogenic attacks increased reliably, while their degree decreased.
      Administration of Semaks "raised" these parameters to the lvl of those in intact
      animals, i.e., increased the sensitivity to sound. Neonatal administration (per
      os) of caffeine to KM rats increased reliably the latent period of audiogenic
      attacks. The thresholds of pain sensitivity in the rats of all strains were
      significantly lower than in the intact control, just as the level of dopamine in
      the hippocampus of KM rats. These data are interpreted as an evidence of changes
      in the development of some brain systems in response to neonatal influences.

PMID- 14714456
TI  - [Mechanisms and frequency of nuclear divisions in trophoblast and decidua cells
      during postimplantation embryogenesis in the mouse].
AB  - The finding of amitotic division of trophoblast cell nuclei in blastocysts of the
      American mink (Mustela vison), which has an obligatory period of delay in
      implantation (obligatory embryonic diapause) in its ontogenesis, led us to study
      the mechanisms and frequencies of division of trophoblast and decidua cell nuclei
      during the postimplantation embryogenesis of mouse (Mus musculus), which does not
      exhibit an obligatory diapause nor amitosis in blastocysts. It has been
      established that the main mechanism underlying the cell nuclei division in both
      tissues (trophoblast and decidua) forming the placenta is amitosis. These data
      suggest that the occurrence of an obligatory embryonic diapause in ontogenesis of
      certain animal species is related not only to the delay in implantation, but also
      to the alteration in the chronology of all processes of embryogenesis.

PMID- 14714457
TI  - [Conjugation mapping of Pseudomonas mendocina bacteria].
AB  - Donor strains of the Hfr type were isolated using plasmid pRK2013 with
      transposons Tn10 and Tn5 as a chromosome-mobilizing factor. The isolated strains
      were shown to promote transfer of donor chromosome from different origins in
      different directions during isogenic matings of Pseudomonas mendocina bacteria.
      The created collection of donors and polyauxotrophic recipient bacteria permitted
      mapping 26 genetic determinants on the bacterial chromosome and identifying the
      genome of these microorganisms as a circular DNA molecule.

PMID- 14714458
TI  - [Construction of a genetic map of Pseudomonas mendocina bacteria].
AB  - Based on the results of matings with interrupted conjugation and analysis of
      marker joint inheritance frequencies, distances between 26 genetic determinants
      were estimated and a genetic map of Pseudomonas mendocina bacteria was
      constructed.

PMID- 14714459
TI  - [Use of molecular markers for differentiation of cultivated strains of oyster and
      button mushrooms].
AB  - Analysis of commercial strains of two edible mushrooms, Pleurotus ostreatus and
      Agaricus bisporus, using PCR and isozyme electrophoresis techniques allowed us to
      differentiate groups of genetically similar and distant strains. Among the
      commercial strains of P. ostreatus, the level of genetic variation was higher
      suggesting a broader genetic basis employed in breeding of this mushroom. The
      cultivars and hybrids of, A. bisporus, showed a higher level of homology. The
      isozyme markers (nonspecific esterase, leucinaminopeptidase, and
      phosphoglucoisomerase) are recommended for identification of the commercial
      strains of edible mushrooms.

PMID- 14714460
TI  - [Genetic and molecular characteristics of a new natural haplotype twMP1 of the
      house mouse (Mus domesticus R.) from Peru].
AB  - A new natural haplotype, twWP1, found in a population of house mouse Mus
      domesticus from Peru, was subjected to genetic and molecular analyses.
      Experiments were performed to study the complementation of the new haplotype,
      fertility of twMP1/tx heterozygotes, and transmission ratio distortion (TRD) of
      the t-carrying chromosome in the progeny of heterozygous males. Molecular
      analysis included blot hybridization with t-specific probes Tu48, Tu66, and
      Tu119. The results were collated with the structure and properties of the t
      complex, and the new haplotype was identified as a complete lethal one.

PMID- 14714461
TI  - [Localization of genes, determining quantitative traits in wheat: amendment to
      the "catalog of chromosomal mapping of genes in domestic cultivars of wheat"].
AB  - An amendment to the catalog of chromosome location of genes in Russian wheat
      cultivars was constructed with the published data of the recent decade. The
      results of chromosomal localization were summarized and analyzed by methods of
      multivariate statistics. Chromosomes critical for 40 quantitative traits under
      study proved to cluster according to their homeology, i.e., by homeological
      groups. The hypotheses providing an explanation for this finding are considered.
      It is suggested that quantitative traits are similarly controlled by genes
      located on homeological chromosomes in common wheat, making it possible to
      isolate a limited number of major genes for each particular quantitative trait.

PMID- 14714462
TI  - [Molecular-genetic polymorphisms of cultivars of common hops (Humulus lupulus L.)
      using ISSR-PCR analysis].
AB  - Genetic diversity among 26 Russian and European cultivars of the common hop
      (Humulus lupulus L.) was studied using the ISSR-PCR technique. Twenty-one primers
      used provided amplification of 183 DNA fragments, 106 of which (57.9%) were found
      to be polymorphic. The ISSR markers, specific for certain cultivars were
      revealed. Based on the coefficient of dissimilarity values, cluster analysis was
      performed and a dendrogram was constructed, on which most of the hop cultivars
      formed two clusters according to their origin. Advantages of the ISSR-PCR
      analysis in selective studies aimed at the classification and identification of
      common hop cultivars are discussed.

PMID- 14714463
TI  - [Cloning a sequence, coding an SKT1 family protease inhibitor from potato].
AB  - Seven structurally similar clones from potato (Solanum tuberosum L.), cv.
      Istrinskii genomic DNA were isolated by cloning of the PCR products. It was
      suggested that five of these clones were the amplified copies of the same gene.
      Based on comparative and structural analysis of these clones, initial nucleotide
      structure of the gene was reconstructed. It appeared to be highly homologous
      (98%) to the already published sequences encoding the proteins belonging to the
      soybean Kunitz trypsin inhibitor family (SKTI). Comparison of the results with
      the previously published data on the SKTI-type proteinase inhibitors from potato
      of cv. Istrinskii suggests that the gene examined encodes both chains of the
      earlier described PSPI-21-6.3 protein [9].

PMID- 14714464
TI  - [Formation of a new original material based on genetic heterogeneity of disomal
      wheat plants from offspring of aneuploids].
AB  - A series of disomic lines of spring wheat Opal selected on the basis of monosomic
      lines of this cultivar has been studied. The lines have been tested for combining
      ability, and the heterosis effect has been studied in disomic lines of F1 hybrids
      obtained by topcrossing. The line have been demonstrated to differ both from one
      another and from cultivar Opal in the expression of quantitative traits,
      combining ability, and the degree of heterosis in F1. These data suggest that
      recombinations accompanying the formation of the monosomic series have changed
      their genetic program. To test this suggestion, intramolecular heterogeneity of
      42-chromosome plants has been analyzed using polymerase chain reaction (PCR) and
      isoenzyme analysis. The results confirmed the differences at the DNA and protein
      levels. According to the results of molecular analyses, A-genome lines are the
      most polymorphic. Strong heterosis effects have been detected in hybrid
      combinations contributed by D- and B-genome lines, which are characterized by
      medium and low degrees of molecular genetic polymorphism. Lines that are
      promising in terms of breeding programs have been identified.

PMID- 14714465
TI  - [Mechanisms of meiotic restitution and their genetic regulation in wheat-rye
      polyhaploids].
AB  - Meiosis has been studied in partially fertile wheat-rye F1 hybrids yielded by
      crosses Triticum aestivum (Saratovskaya 29 variety) x Secale cereale L.
      (Onokhoiskaya variety) (4x = 28). Hybrid self-fertility proved to be caused by
      formation of restituted nuclei, which appear after equational segregation of
      univalent chromosome in AI and sister chromatid non-separation in AII of meiosis,
      as well as after AI blockage in three different ways. Both types of meiotic
      restitution were found in each hybrid plant. Expression of the "meiotic
      restitution" trait varied significantly in polyhaploids of the same genotype
      (ears of the same plants, anthers of the same ear, microsporocytes of the same
      anther). Chromatin condensation in prophase proved to be related to the division
      type and univalent segregation in AI. During reduction segregation of univalents
      in AI, sister chromatid cohesion and chromosome supercondensation remained
      unchanged. The results obtained suggest that in the remote hybrids with haploid
      karyotype of the parental origin (polyhaploids), the program of two-stage meiosis
      may be fundamentally transformed to ensure one instead of two divisions. We
      propose that meiotic restitution is a result of special genetic regulation of the
      kinetochore organization (both structural and functional) and chromatin
      condensation, i.e. of major meiotic mechanisms.

PMID- 14714466
TI  - [Genetic diversity of carrion and jungle crows from RAPD-PCR analysis data].
AB  - RAPD-PCR analysis of the genetic diversity of the carrion crow (Corvus corone)
      and jungle crow (C. macrorhynchos) living in the continental parts of their
      species ranges and on some Russian and Japanese Far Eastern islands has been
      performed. Taxon-specific molecular markers have been found for each species. The
      genetic diversity of the carrion crow is considerably less than that of the
      jungle crow at the same genetic distance (P95 = 68.2%, DN = 0.27 and P95 = 88.4%,
      DN = 0.24, respectively). In both species, the genetic polymorphism of island
      samples is almost two times greater than that of continental samples (62 and
      31.8%, respectively, for C. corone and 81.5 and 47.2%, respectively, for C.
      macrorhynchos). In addition, differences in genetic diversity between males and
      females (P95 = 55.1 and P95 = 72.1, respectively) has been found in the carrion
      crow but not in the jungle crow. The gene diversity of C. macrorhynchos is
      greater than that of C. corone: the mean numbers of alleles per locus are 2 and
      1.81, effective numbers of alleles are 1.62 and 1.43, and the mean expected
      heterozygosities are 0.39 and 0.30, respectively. The phenograms and phylograms
      significantly segregate the clusters of the carrion and jungle crows. The
      clustering patterns of carrion crows corresponds to the intraspecies taxonomic
      and geographic differentiation: subspecies C. c. corone and C.c. orientalis
      living in the western and eastern parts of the species range, respectively, form
      different subclusters. The cluster of the jungle crow does not exhibit
      differentiation into subspecies C. m. mandshuricus and C. m. japonensis;
      molecular genetic differences between them are small.

PMID- 14714467
TI  - [Molecular evolution of satellite DNA CLsat in lizards of the Darevskia species
      (Sauria: Lacertidae): correlation with species diversity].
AB  - The structure and evolution of a satellite DNA family was examined in lizards
      from the genus Darevskia (family Lacertidae). Comparison of tandem units of
      repeated DNA (satDNA), CLsat, in all species from the genus Darevskia has shown
      that their variability is largely based on single-nucleotide substitutions, which
      constitute about 50 diagnostic positions underlying classification of the family
      into three subfamilies. Maximum differences between the subfamilies reached 25%.
      At this level of tandem unit divergence between the subfamilies, no cross
      hybridization between them was observed (at 65 degrees C). The individual
      variability of one subfamily within the species was on average 5% while the
      variability between species consensuses within a subfamily was 10%. The presence
      of highly conserved regions in all monomers and some features of their
      organization show that satellites of all Darevskia species belong to one satDNA
      family. The organization of unit sequences of satellites CLsat and Agi also
      detected by us in another lizard genus, Lacerts s. str. was compared. Similarity
      that was found between these satellites suggests their relatedness and common
      origin. A possible pathway of evolution of these two satDNA families is proposed.
      The distribution and content of CLsat repeat subfamilies in all species of the
      genus was examined by Southern blotting hybridization. Seven species had mainly
      CLsatI (83 to 96%); three species, approximately equal amounts of CLsatI and
      CLsatIII (the admixture of CLsatII was 2-3%); and five species, a combination of
      all three subfamilies in highly varying proportions. Based on these results as
      well as on zoogeographic views on phylogeny and taxonomy of the Darevskia
      species, hypotheses on the evolution of molecular-genetic relationships within
      this genus are advanced.

PMID- 14714468
TI  - [Analysis of intragenic polymorphic markers of the CFTR gene in cystic fibrosis
      patients and health donors from Bashkorostan].
AB  - The differences in the polymorphic allele frequency distribution patterns of the
      biallelic (M470 and TUB20) and microsatellite (IVS6aGATT, IVS8CA, and IVS17CA)
      markers within the CFTR gene between normal and delF508 chromosomes have been
      established. For most of the marker loci similar distribution of the allele
      frequencies on normal and mutant chromosomes without delF508 was demonstrated.
      Certain polymorphic alleles displayed substantial linkage disequilibrium with the
      delF508 mutation. Analysis of the IVS6aGATT-IVS8CA-M470-IVS17CA-TUB20 haplotypes
      association on normal and mutant chromosomes provided identification of the
      delF508 ancestral haplotype. It was suggested that delF508 mutant chromosomes
      were introduced into the modern Bashkir gene pool as a result of Slavic
      migrations from the Eastern Europe. The IVS6aGATT-IVS8CA-M470-IVS17CA-TUB20 major
      haplotype (77272) revealed was statistically significantly most frequently found
      on the mutant chromosomes without the delF508 mutation. This finding suggests
      that the Bashkir cystic fibrosis patients, mostly belonging to the Turkic
      speaking families, possessed specific CF gene defect associated with the given
      haplotype.

PMID- 14714469
TI  - [Population-genetic structure of Chuvashia (from data on eight DNA loci in the
      nuclear genome)].
AB  - Population-genetic study of indigenous populations representing three ethnic
      Chuvash group: highland (Cheboksarsk and Morgaush district), lowland (Kanash
      district) and mid-lowland (Marposad district). Eight polymorphic DNA loci of the
      nuclear genome (VNTR/PAH, STR/PAH, VNTR/ApoB, VNTR/DAT1, APF, VNTR/eNOS,
      IVS6aGATT, and KM.19/PstI) were examined in the population of each district. For
      each of the four population, we estimated the allele and genotype frequency
      distributions at each polymorphic system, heterozygosities HS and between
      population differences FST. In the combined Chuvash sample, HS = 0.464 and FST =
      0.006. Loci VNTR(DAT) and VNTR(ApoB) showed highest between-population
      differentiation (0.009 < or = FST < or = 0.012), and loci IVS6aGATT, APF,
      VNTR/eNOS, and D7S23 (KM.19), lowest differentiation (0.001 < or = FST < or =
      0.003). Analysis of genetic distances revealed somewhat higher genetic similarity
      between the Cheboksarsk and Morgaush populations belonging to the highland
      Chuvash group, whereas the highland Chuvash population from the Marposad
      district, which belong to the mid-lowland group, was more distant from the former
      populations.

PMID- 14714470
TI  - [Comparative phylogenetic study of native north Eurasian populations from a panel
      of autosomal microsatellite loci].
AB  - Genetic relationships among eighth Siberian and Central Asian ethnic groups were
      examined using autosomal microsatellite loci. Genetic similarity of Buryats and
      Evenks, as well as close relationships between Tuvinians and Kyrgyzes, most
      likely resulting from the Altai-Slavic co-ancestry of their gene pools, was
      demonstrated. Studies of gene flow in these populations demonstrated that, in
      general, Turkic ethnic groups of Southern Siberia (Altaians and Tuvinians) were
      the recipients of more intense gene flow compared to Eastern Siberian populations
      belonging to Altaic family. The local Buryat populations displayed substantial
      differences in the direction and the level of deviation of the observed gene
      diversity from the expected one, which was probably caused by the differences in
      the degree of isolation and/or in effective population sizes.

PMID- 14714471
TI  - [Genetic structure of the Iranian-speaking population of Azerbaijan from data on
      frequencies of immunologic and biochemical gene markers].
AB  - The data on the genetic studies of Iranian-speaking populations from Azerbaijan
      (Talyshs and Tats) are presented. In these populations gene frequency
      distributions for the immunological (AB0, MN, Rhesus-D, -C, -E, P, Lewis, and
      Kell-Chellano) and biochemical (HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP1, and PGM1)
      gene markers were determined. Comparison of the genetic structure of the
      populations examined with the other Iranian-speaking populations (Persians and
      Kurds from Iran, Ossetins and Tajiks) and Azerbaijanis showed that Iranian
      speaking populations from Azerbaijan were more close to Azerbaijanis, than to
      Iranian-speaking populations inhabiting other world regions.

PMID- 14714473
TI  - [Identification of catalytically active groups in inulinase from Bacillus
      polymyxa 722].
AB  - Inulinase from Bacillus polymyxa 722 hydrolyzing a polyfructosan inulin was
      studied. The dependence of inulinase activity on pH, measurements of pK value,
      calculation of ionization heat, photoinactivation with methylene blue, and
      inhibition with p-chloromercuribenzoate suggest that the active center of this
      enzyme contains imidazole and sulfhydryl groups. A possible mechanism underlying
      cleavage of beta-2,1-fructoside bonds in the inulin molecule with inulinase is
      considered.

PMID- 14714472
TI  - [Methionine sulfoximine and phosphinothricin--glutamine synthetase inhibitors and
      activators and their herbicidal activity (A review)].
AB  - Derivatives of methionine sulfoximine (MSO) and phosphinothrycin (PPT), which are
      analogues of glutamate, exhibit selective herbicidal activity. This effect is
      accounted for by impairments of nitrogen metabolism, resulting from inhibition of
      its key enzyme in plants, glutamine synthetase (EC 6.3.1.2). Inhibition of the
      enzyme causes ammoniac nitrogen to accumulate and terminates the synthesis of
      glutamine. Changes in the content of these two metabolites (excess ammonium and
      glutamine deficiency) act in a concert to cause plant death. However, low
      concentrations of MSO, PPT, and their metabolites produce an opposite effect:
      glutamine synthetase is activated, with concomitant stimulation of plant growth
      and productivity. The mechanisms whereby MSO and PPT affect glutamine synthetase
      activity are discussed in the context of nitrogen metabolism in plants.

PMID- 14714474
TI  - [Isolation and purification of bovine testicular hyaluronidase].
AB  - We developed a single-step method for chromatographic purification of the
      hyaluronidase extract on Sepharose blue, which produced high yield of the enzyme
      (95%) with high purity (40). Purification of hyaluronidase allowed us to obtain
      biological preparations standardized by the protein composition and enzyme
      activity and useful for basic and applied researches.

PMID- 14714475
TI  - [Noncompetitive immunochemical determination of ribonuclease using transition
      metal ions and the effect of catalytic hydrogen release].
AB  - A noncompetitive variant of immunochemical ribonuclease (RNase) determination has
      been developed, involving the use of Co(II) as a label. A variety of approaches
      to labeling the immunological reagent with the metal have been assessed. In the
      variant proposed, catalytic hydrogen release was used as a means of detecting the
      label, the amount of which was proportional to RNase concentration. Conditions
      making it possible to record catalytic hydrogen release fluxes were determined.
      In the presence of RNase, the electrocatalytic effect was maximum at a
      concentration of Co(II) in the ammoniac buffer, equal to 2 x 10(-4) M (pH 10.0).
      The dependence was linear in the range 4-2000 ng/ml RNase concentrations
      (threshold concentration, 2 ng/ml).

PMID- 14714476
TI  - [Kinetics of protein hydrolysis during the induced autolysis of the Saccharomyces
      cerevisiae biomass].
AB  - The kinetics of the initial stages of autolysis of the yeast Saccharomyces
      cerevisiae was studied and the following kinetic parameters were determined:
      induction period, steady-state rate of the enzyme-induced effect, and steady
      state concentration of intermediate products. It was shown that appropriate
      inducers were able to cause a more than fourfold increase in the rate of
      reactions catalyzed by proteinases and almost a tenfold increase in the
      concentration of intermediate peptides. The mean length of the peptide molecules
      formed in the process was determined and dependence of this value on the degree
      of hydrolysis was demonstrated.

PMID- 14714477
TI  - [Isolation and characterization of a cellobiose dehydrogenase formed by a
      asporogenic mycelial fungus INBI 2-26(-)].
AB  - A nonsporulating fungus isolated from dioxine-containing tropical soils forms
      cellobiose dehydrogenase, when grown in media supplemented by a source of
      cellulose. The enzyme purified to homogeneity by SDS-PAGE (yield, 43%) had an
      M(r) of 95 kDa; its pH optimum was in the range 5.5-7.0; more than 50% activity
      was retained at pH 4.0-8.0 (citrate-phosphate buffer). The absorption spectrum of
      the enzyme in the visible range had the characteristic appearance of
      flavocytochrome proteins. Cellobiose dehydrogenase oxidized cellobiose and
      lactose (the respective K(M) values at pH 6.0 equaled 4.5 +/- 1.5 and 56 microM)
      in the presence of dichlorophenolindophenol (K(M) app = 15 +/- 3 microM at pH
      6.0) taken as an electron acceptor. Other sugars were barely if at all oxidized
      by the enzyme. Neither ethyl-beta-D-cellobioside, heptobiose, nor chitotriose
      inhibited the enzymatic oxidation of lactose, even under the conditions of 100
      fold molar excess. The enzyme was weakly inhibited by sodium azide
      dichlorophenolindophenol reduction and exhibited affinity to amorphous cellulose.
      At 55 degrees C and pH 6.0 (optimum stability), time to half-maximum inactivation
      equaled 99 min. The enzyme reduced by cellobiose was more stable than the
      nonreduced form. Conversely, the presence of an oxidizer
      (dichlorophenolindophenol) decreased the stability eight times at pH 6.0. In
      addition, the enzyme acted as a potent reducer of the single-electron acceptor
      cytochrome c3+ (K(M) app = 15 microM at pH 6.0).

PMID- 14714478
TI  - [Biosynthesis of hydrolytic enzymes during cocultivation of macro- and
      micromycetes].
AB  - Effects of co-cultivation of higher Basidiomycetes and Phycomycetes on the
      biosynthesis of cellulases, amylases, and proteases was studied. Four optimal
      pairs of fungal cultures were selected. Of these, three pairs belonged to higher
      fungi, and one pair was constituted by fungi of distinct ecological groups, a
      macromycete and a micromycete. The activities of amylase and protease were 1.5 to
      2 times higher, and the activity of cellulase was lower during the growth of
      higher fungi associations. The mixed association of the macromycete Schizophyllum
      commune and the micromycete Mucor sp. was the most active producer of hydrolytic
      enzymes. During the growth of this mixed association, a fourfold and 1.5-fold
      increases were observed in the activity of endoglucanase and protease,
      respectively, paralleled by stimulation of amylase formation.

PMID- 14714479
TI  - The action of Cu2+ on Bacillus thuringiensis growth investigated by
      microcalorimetry.
AB  - By using an LKB-2277 Bioactivity Monitor, ampoule mode, the heat output of
      Bacillus thuringiensis growth metabolism has been determined at 28 degrees C and
      effect of Cu2+ on B. thuringiensis growth was studied. Copper has been regarded
      as an essential trace element for life. Its deficiency may be the cause of
      diseases. Cu2+ of different concentration have different effects on B.
      thuringiensis growth metabolism, Cu2+ of low concentration (0-30 micrograms/ml)
      can promote the growth of B. thuringiensis, and Cu2+ of high concentration (40
      120 micrograms/ml) is able to inhibit its growth and B. thuringiensis can't grow
      at all when the concentration of Cu2+ is up to 130 micrograms/ml.

PMID- 14714480
TI  - [Isolation of hydrocarbon-oxidizing psychrophilic bacteria from oil-polluted
      soils].
AB  - Microorganisms growing on a mineral medium with crude oil and its light fractions
      as only carbon and energy sources have been isolated from samples of oil-polluted
      soils collected in the Usa District (Komi Republic, Russia). For the first time,
      hydrocarbon-oxidizing psychrophilic bacteria of the genus Cytophaga have been
      found that are clearly capable of consuming crude oil hydrocarbons. A method for
      cultivating microorganisms on porous plastic is proposed. The data from the
      literature on the response of soil microbiota to oil pollution indicate that the
      pollution can activate or suppress the growth of various physiological groups of
      microorganisms [1]. Different soil and climatic conditions and pollution levels
      can give rise to different microbial cenoses, which include different
      associations and predominant microbial species.

PMID- 14714481
TI  - [Degradation of bis(2-ethylhexyl)phthalate by microorganisms of water and
      sediments of the Selenga river and Baikal Lake under experimental conditions].
AB  - Degradation of bis-(2-ethylhexyl)phthalate (BEHP) by microbial associations of
      water and bottom sediments of the Selenga River and Lake Baikal and by pure
      cultures of microbial species belonging to various taxa isolated from the
      sediments under discussion has been studied. It has been shown that intense
      biological degradation occurs in both water and sediments. The degrees of
      conversion in experimental closed systems on minimal media are 46 and 24%,
      respectively. The most active of the organisms studied is a Micromironospora
      actinomycete. It degraded BEHP by 36% of its initial concentration. Spore-forming
      bacteria and microorganisms of the genus Pseudomonas were less active (17-23% and
      7-11%).

PMID- 14714482
TI  - [Biochemical characterization of aeromonad strains differing in pathogenicity].
AB  - A virulent strain of motile aeromonad (77-18) and an avirulent strain (78-16)
      differed in the contents of lipids and phospholipids, odd fatty acids, activity
      of hydrolytic enzymes, and amount of proteins with molecular weights of 47-56
      kDa. It is assumed that proteins with molecular weights of 47-56 kDa, proteolytic
      enzymes active within a wide pH range, and odd fatty acids may act as
      pathogenicity factors. Each of these compounds or their combination determines
      certain stage of infection.

PMID- 14714483
TI  - [Inhibitory effect of antimicrobial preparation from lipids of marine fishes on
      tissue and microbial enzymes].
AB  - We obtained a new food preservative from marine fish lipids possessing pronounced
      activity in relation to bacteria and microscopic fungi. The effects of this
      preparation on enzymes of microorganisms and muscle tissue of marine hydrobionts
      were studied. In vitro the preparation irreversibly inhibited acid and alkaline
      proteases and proteolytic and lipolytic enzymes of microorganisms and reduced
      enzyme activity in fish muscle tissue. The inhibitory effect of this preparation
      on enzymes contributes to stabilization of hydrolytic processes in meat of
      hydrobionts and suppresses microorganism growth in storage.

PMID- 14714484
TI  - [Efficiency of alfalfa and reed in the phytoremediation of hydrocarbon polluted
      soil].
AB  - The efficacy of plants as means of decontaminating hydrocarbon-polluted soil has
      been studied. Ditch reed (Phragmites australis) and alfalfa (Medicago sativa)
      markedly intensified processes of pollutant destruction, the effect being
      particularly pronounced in the case of polycyclic aromatic hydrocarbons (PAHs).
      Comparative analysis of microflora in soils (including those devoid of plants and
      rhizosphere) demonstrated that, in addition to preventing the pollutant-induced
      decrease in the amount of heterotrophic microorganisms, the plants stimulated
      their development, significantly increasing the population of destructors.
      Effects of plants on major physiological groups of soil microorganisms under
      conditions of pollution were ambiguous. The rhizosphere consortium of alfalfa was
      less susceptible to effects of pollutants than that of reed.

PMID- 14714485
TI  - [Photosynthetic pigments of tomato under conditions of biotic stress and effects
      of furostanol glycosides].
AB  - Adaptogenic effect of furostanol glycosides (FG) on biosynthesis of
      photosynthetic pigments in tomato plants (Lycopersicon esculentum Mill.) were
      studied under conditions of biotic stress caused by root-knot nematode
      (Meloidogyne incognita Kofoid et White). Treatment of plants with 5 x 10(-4) M FG
      was accompanied by an increase in the rate of biosynthesis of pigments
      (particularly, chlorophyll b and carotenoids), which was observed against the
      background of a decrease in the relative contribution of beta-carotene and an
      increase in the relative contribution of pigments of violaxanthin cycle (VXC) to
      the overall pool of carotenoids. It was suggested that FG stimulated
      phytoimmunity by shifting metabolism of carotenoids toward enhanced biosynthesis
      of VXC pigments. These pigments play a protective role and facilitate
      stabilization of photosynthetic apparatus, which is particularly important under
      stress conditions.

PMID- 14714486
TI  - [Regulation of potato immune responses by laminarin].
AB  - Laminarin blocks potato immune responses by inhibiting the reaction of
      oversensitivity, formation of phytoalexins, wound repair, and the activity of
      proteinase inhibitors. It was found that laminarin exhibits antielicitor
      activity. Addition of salicylic acid to laminarin enhances its immunosuppressing
      effect, which becomes systemic.

PMID- 14714487
TI  - [Effect of the composition of polysaccharides in gelatinized cornstarch on
      alcohol absorption].
AB  - Sorption of alcohols in aqueous suspensions of gelatinized cornstarches with
      various contents of amylose was studied by capillary gas chromatography. Alcohol
      sorption depended primarily on the structure of alcohols, but not on the
      composition of polysaccharides. No correlation was found between the efficiency
      of sorption and amylose content in starch. The amount of substances sorbed by
      starches depended linearly on their initial concentration in the gel. Normal and
      highly amylose starches sorbed alcohols to a similar degree. However, increasing
      the length of alkyl substituents improved sorption of alcohols. Amylopectin
      starch differed in high affinity for small molecules and low sensitivity to the
      structure and hydrophobicity of alcohols.

PMID- 14714488
TI  - [First class transcription termination factors--functional analogs of aminoacyl
      tRNA].
AB  - Reviewed and discussed are the recent data demonstrating profound functional
      similarity between class-1 translation termination factors (RF1 and RF2 in
      prokaryotes, aRF1 and eRF1 in Archaea and eukaryotes, respectively) and aminoacyl
      tRNA as regards their roles in the course of translation on the ribosome.
      Functional analogy of these two components of the cell protein-synthesizing
      machinery was suggested long ago; however, numerous experimental proofs have been
      obtained only recently. This similarity implies that decoding of the genetic
      information by the ribosomal machine is performed similarly at all stages of
      translation, though tRNA plays the main role at initiation and elongation, while
      the protein is most important for termination. Earlier it was found that nucleic
      acids (ribozymes) can operate like the protein enzymes, and now we have got
      evidence for the reverse: a protein (translation termination factor) can act like
      a nucleic acid (tRNA). Thus one can speak of "exchange" of molecular functions
      between proteins and nucleic acids. Therefore, the profound chemical difference
      between proteins and nucleic acids is not an insuperable barrier to their mutual
      functional replacement in certain situations.

PMID- 14714489
TI  - [Enzymes of direct, excision, and corrected systems of repair of higher and lower
      organisms and their biological roles].
AB  - DNA repair is of paramount importance to protect the integrity of the cell
      genome. Over the last decade, DNA repair enzymes have been intensely studied
      owing to their role in mutagenesis, carcinogenesis, and aging. This led to
      discoveries of novel enzymes, protein factors as well as their intermolecular
      complexes involved in the repair process. Alternative pathways of cell response
      to the same type of damage were identified. Data on the tertiary structure of a
      number of enzymes and mechanisms of their molecular interaction were obtained.
      This paper is an overview of latest advances in the research of cell response to
      DNA damage via direct, base and nucleotide excision, and mismatch DNA repair.

PMID- 14714490
TI  - [Analysis of polymorphic loci of Huntington genes in peoples from the Volga-Ural
      region].
AB  - Eleven populations of the Volga-Ural region were analyzed with respect to three
      intragenic polymorphisms of the Huntington disease gene (IT15), including highly
      polymorphic (CAG)n and moderately polymorphic (CCG)n of exon 1 and neutral
      del2642 of exon 58. In the case of (CAG)n, 101 genotypes were observed, with
      genotype number varying from 15 in Southeastern Bashkirs to 34 in Mari. Allele
      diversity RS ranged from 9.70 in Southeastern Bashkirs to 18.00 in Chuvash,
      averaging 13.79 +/- 2.12. The (CAG)n allele frequency distribution was unimodal
      and had a maximum at (CAG)17. In the case of (CCG)n, six alleles with 6-10 or 12
      repeats were observed. RS was 4.13 +/- 0.44, ranging from 3.73 in Udmurts to 4.99
      in Tatars. In the case of del2642, allele del- was detected at a frequency 0.830
      in Mari to 0.932 in Udmurts. Of all Volga-Ural ethnic populations, Finno-Ugric
      ones proved to be most heterogeneous with respect to the three polymorphisms,
      whereas Turkic populations and, in particular, Bashkirs were homogeneous. Micro
      differentiation of the Volga-Ural populations corresponded to the European type.

PMID- 14714491
TI  - [Polymorphism of arylamine-N-acetyltransferase 2 gene in peoples of the Volga
      Ural region].

PMID- 14714492
TI  - [Association of polymorphism of genetic markers of CYP19 and CYP17 with sporadic
      breast cancer].
AB  - Polymorphic alleles of CYP17 and CYP19, which are involved in estrogen
      biosynthesis, were tested for association with breast cancer (BC). Microsatellite
      (TTTA)n and 3-bp deletion of CYP19 and single-nucleotide polymorphism T27C of
      CYP17 were analyzed in 123 BC patients and 119 healthy women. Of the six (TTTA)n
      alleles observed, allele (TTTA)8 proved to be associated with BC (11.8% vs. 6.3%,
      P = 0.04). Genotype A2/A2 of CYP17 was also associated with BC (32.5% vs. 20.2%,
      P = 0.04). Risk of BC was especially high in the presence of both factors (7.3%
      vs. 0%, P < 0.01). Allele (TTTA)8 and genotype A2/A2 were assumed to be risk
      factors of BC.

PMID- 14714493
TI  - [Profile of methylation of certain tumor growth suppressing genes in non-small
      cell lung cancer].
AB  - Multiplex methylation-sensitive PCR was employed in studying the methylation of
      CpG islands in the RB1, p16/CDKN2A, p15/CDKN2B, p14/ARF, CDH1, HIC1, and N33 5'
      regions in non-small cell lung cancer (51 tumors). Methylation was observed for
      the two suppressor genes involved in controlling the cell cycle through the Cdk
      Rb-E2F signaling pathway, RB1 (10/51, 19%) and p16 (20/51, 39%). The highest
      methylation frequencies were established for CDH1 (72%) and HIC1 (82%). The CpG
      islands of p14 and p15 proved to be nonmethylated. At least one gene was
      methylated in 90% (46/51) tumors and no gene, in 10% (5/51) tumors. In addition,
      the genes were tested for methylation in peripheral blood lymphocytes of healthy
      subjects. Methylation frequency significantly differed between tumors and normal
      cells in the case of RB1, p16, CDH1, HIC1, and N33. Gene methylation frequency
      was tested for association with histological type of the tumor and stage of tumor
      progression. Methylation index of a panel of tumor suppressor genes was
      established for groups of tumors varying in clinical and morphological
      parameters.

PMID- 14714494
TI  - [Thermostability of alkaline phosphatase of Meithermus ruber bacteria: cloning of
      the gene, expression in Escherichia coli cells and biochemical characterization
      of the recombinant protein].
AB  - The Meiothermus ruber alkaline phosphatase gene was cloned, expressed in
      Escherichia coli cells, and sequenced. The enzyme precursor, including the
      putative signal peptide, was shown to consist of 503 residues (deduced molecular
      mass 54,229 Da). The recombinant enzyme showed the maximal activity at 60-65
      degrees C and pH 11.0 and had K(m) = 0.055 mM as estimated with p-nitrophenyl
      phosphate (pNPP). The enzyme proved to be moderately thermostable, retaining 50%
      activity after 6 h incubation at 60 degrees C and being completely inactivated in
      2 h at 80 degrees C. In substrate specificity assays, the highest enzymic
      activity was observed with pNPP and dATP. Vanadate, inorganic phosphate, and SDS
      inhibited M. ruber alkaline phosphatase, while thiol-reducing agents had
      virtually no effect. The enzymic activity strongly depended on exogenous Mg2+ and
      declined in the presence of EDTA.

PMID- 14714495
TI  - [Polymorphism of length of tetranucleotide repeat from the 5'-side from the
      myelin basic protein gene in multiple sclerosis in Russians].
AB  - The myelin basic protein gene (MBP) can confer the susceptibility to multiple
      sclerosis, because its protein product is the main protein component of myelin of
      the central nervous system and a potential autoimmune antigen in the disease. A
      possible association of multiple sclerosis with alleles and genotypes of a
      microsatellite repeat (TGGA)n, located to the 5' side from the first exon of MBP
      in ethnic Russians (126 patients with reliable multiple sclerosis and 142 healthy
      controls from Central Russia) was analyzed using the case-control method. Upon
      separation of the tetranucleotide repeat site amplification products in 1.5%
      agarose gel, one can see two distinct bands that can be analyzed as two allele
      groups (A and B). The distribution of allele A and B group frequencies as well as
      frequency of allele group B and genotype A/A reliably differs in multiple
      sclerosis patients and healthy controls. Alleles A and the A/A genotype are
      associated with the development of multiple sclerosis. We also analyzed the
      association of multiple sclerosis with combined bearing of alleles and genotypes
      A and B of MBP and groups of alleles of the DRB1 gene of the major
      histocompatibility complex that correspond to serospecificities DR1-DR18. The
      comparison of subgroups of multiple sclerosis patients and healthy individuals,
      formed on the basis of the DRB1 phenotype, has shown a reliable increase in the
      frequency of allele B in healthy individuals and the genotype A/A frequency in
      patients, only among DR4- and DR5-positive individuals. No reliable difference
      was found in the MBP allele and genotype distribution between multiple sclerosis
      patients and healthy individuals in combined groups of (DR4,DR5)-negative
      individuals, i.e., no carriers of any phenotype except DR4 and DR5 were revealed.
      Thus, MBP or some other nearby gene is involved in the multiple sclerosis
      development in Russians, predominantly (or exclusively) among DR4 and DR5
      carriers. In this case, without stratification of analyzed individuals by the MBP
      alleles, multiple sclerosis is reliably associated only with DR2(15), but not of
      DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic
      heterogeneity of multiple sclerosis, and suggest the possibility of epistatic
      interactions between the MBP and DRB1 genes.

PMID- 14714496
TI  - [Construction of a reporter system for fine quantitative assessment of activity
      of p53 protein in cultured cells].
AB  - Since transcriptional activation of genes downregulating cell proliferation
      mediates the tumor suppressor activity of p53, induction of p53 targets was
      assumed to adequately reflect the state of p53-dependent pathways. To estimate
      the p53 activity in cultured cells, self-inactivating retrovirus constructs pSIP
      ConA-GFP and pSIP-ConA-LacZ were obtained to express the GFP or beta
      galactosidase reporter gene under the control of a promoter containing p53
      responsive elements. The advantages of these constructs were efficient delivery,
      comparable expression in different cells of a culture, and, consequently, the
      possibility of quantitating the p53 activity induced by various agents. With pSIP
      ConA-LacZ, p53 activation in response to 12 chemotherapeutic agents was analyzed
      in human carcinoma cell line HCT116 and its derivatives HCT116/mdm2 and
      HCT116ARF, which expressed genes affecting the p53 activity. The analysis was
      also carried out with human cell lines HEF, WI-38, U2OS, and HT1080 originating
      from connective tissue. The construct proved suitable for detecting fine
      differences in p53 activation induced by various stress factors. The constructs
      were proposed for generating reporter cell lines from various cultures in order
      to identify the genetic or chemical factors that modulate the p53 activity and
      may be employed in new antitumor drugs.

PMID- 14714497
TI  - [Arrangement of the sense and terminating codons of the template in the A-segment
      of human ribosomes from photocrosslinking data withe oligonucleotide
      derivatives].
AB  - Oligoribonucleotide derivatives containing Phe codon UUC along with a 3'-flanking
      sense codon or stop codon carrying a perfluoroarylazido group at G or U were used
      to study the position of each nucleotide of the latter codon relative to the 18S
      rRNA in the A site of the 80S ribosome. To place the modified sense or stop codon
      in the A site, UCC-recognizing tRNA(Phe) was bound in the P site. Regardless of
      the position in the sense or stop codon, the modified nucleotide crosslinked with
      invariant dinucleotide A1823/A1824 or nucleotide A1825 in helix 44 close to the
      3' end of the 18S rRNA. Located in the second or third position of either codon,
      the modified G bound with invariant nucleotide G626, which is in the
      evolutionarily conserved 530 stem-loop segment. The results were collated with
      the X-ray structure of the bacterial ribosome, and the template codon was assumed
      to be similarly arranged relative to the small-subunit rRNA in various organisms.

PMID- 14714498
TI  - [Approach to identifying the functionally important segments of RNA, based on
      complementation-addressed modification].
AB  - An approach based on complementation-addressed modification of nucleic acids by
      oligodeoxyribonucleotide derivatives was proposed for changing the spatial
      structure of particular RNA sites in order to study their role in the biological
      activity of the total RNA molecule. Hepatitis C virus (HCV) IRES was used as a
      model. Oligodeoxyribonucleotide derivatives contained a 4-[N-(2-chloroethyl)-N
      methylamino]benzylamino group at the 5'-P and were complementary to various RNA
      sites located in regions of hairpins II, IIId, or IIIe. Covalent adducts
      resulting from RNA alkylation with the derivatives were isolated by denaturing
      PAGE and tested for binding with the 40S subunit of human ribosomes. Structural
      alteration of hairpin II had no effect, whereas alteration of hairpin IIIe
      substantially reduced the binding. The RNA with modified hairpin IIId showed
      virtually no binding with the 40S subunit. Hairpin IIId was assumed to play a
      critical role in the binding of HCV IRES with the 40S subunit.

PMID- 14714499
TI  - [Trans- and cis-acting autorepressors of the prqR gene in Synechocystis
      cyanobacteria sp. PCC6803].
AB  - Genetic analysis of the allele interactions was carried out with the use of
      recombinant plasmids and reporter genes to study the autorepressor function of
      prqR, which negatively regulates the prqR-prqA operon and the response to
      oxidative stress inductor methyl viologen (MV) in cyanobacterium Synechocystis
      sp. PCC 6803. The wild-type (WT) prqR showed negative autoregulation and
      suppressed in trans the derepressed mutant alleles. Frameshift mutation C134fs,
      which was introduced in prqR by site-directed mutagenesis, impaired the
      autoregulation, implicating the C-terminal domain in transcriptional repression
      by PrqR. Missense mutation C134S altering the only redox-sensitive Cys of PrqR,
      had no effect on prqR expression, indicating that oxidation and consequent
      disulfide bridging of two PrqR molecules was not responsible for MV-induced
      autorepression of prqR. Analysis of the prqR-prqA deletion derivatives lacking
      the promoter and most of prqR revealed weak uncontrollable expression of reporter
      cat, testifying to the existence of a constitutive promoter in prqA responsible
      for MV resistance. The interaction of the WT and mutant prqR alleles in
      Synechocystis cells revealed a cis-dominant character of the alteration of prqR
      autoregulation. Stimulation of in cis autorepression of prqR was assumed to
      contribute to the induction of systems protecting cyanobacteria from oxidative
      stress.

PMID- 14714500
TI  - [Interaction of topotecan-a DNA topoisomerase I inhibitor-with dual-stranded
      polydeoxyribonucleotides. V. Topotecan is able to cause single- and double-strand
      breaks in ring superhelical DNA in the absence of enzyme].
AB  - Temperature, concentration, and time dependence for the emergence of breaks in
      the sugar-phosphate backbone in a circular supercoiled DNA (scDNA) was studied
      for the first time in the presence of topotecan (TPT) and in the absence of human
      DNA topoisomerase I (topo I). Because TPT is a comptothecin (CPT) derivative, it
      is the first example for the ability of molecules of CPT family to cause double
      stranded breaks in scDNA in the absence of the enzyme. The experiments were
      carried out in low ionic strength solutions (10 mM sodium cacodylate) at neutral
      pH (6.8). Incubation time necessary for the appearance of double-stranded breaks
      in scDNA in the presence of TPT correlated with the time of formation of strong
      TPT-DNA complex. A model was suggested for the complex composed of two crossed
      DNA duplexes bound through a bridge of two dimers of TPT lactone form. According
      to this model, two carbonyl groups of D rings of different TPT dimers form
      hydrogen bonds with 2-amino groups of guanines located in the neighboring base
      pairs of diverse strands of one of DNA duplexes. At the same time, two other
      carbonyl groups of D rings of TPT dimers form hydrogen bonds with 2-amino groups
      of guanines spaced five bp apart in the same strand of the second DNA duplex.

PMID- 14714501
TI  - [Guanidine hydrochloride mediated unfolding of a carbonic anhydrase molten
      globule].
AB  - Guanidine hydrochloride-induced unfolding of a carbonic anhydrase molten globule
      was studied by high-resolution NMR spectroscopy. The study resulted in estimation
      of the number of water and denaturant molecules bound to the molten globule at
      various denaturant concentrations in solution. When compared with the data on
      unfolding of native carbonic anhydrase, these estimates indicate that the
      unfolding is underlain by an increased local concentration of the denaturant near
      the protein molecule, which results from the increased ratio between guanidine
      hydrochloride-bound and protein-bound waters.

PMID- 14714502
TI  - [Dye with low specificity to nucleotide sequences of DNA: use for assessing the
      quantity of oligonucleotides, immobilized in cells of biological microchips].
AB  - To assess the DNA amount in samples (e.g., in biological microchip gel pads) by
      means of fluorescent dyes, one should use the dyes whose fluorescence weakly
      depends on DNA composition and structure. With the ImD-310 dye created for this
      purpose, we have analyzed the staining of single- and double-stranded oligo- and
      polynucleotides of different nucleotide composition, length, and concentration
      both in solution and being immobilized in biological microchip gel pads. It
      turned out that ImD-310 has no pronounced specificity to the single- and double
      stranded nucleotide sequences, while the intensity of fluorescence for the dye
      complexes with d(A)8, d(T)8, d(C)8, and d(G)8 at high temperatures (50 degrees C)
      differs by less than 25%. A linear correlation has been established between the
      intensity of fluorescence and the amount of oligonucleotides immobilized on a
      biological microchip. The plots of the intensity of fluorescence against the
      concentration of NaCl and the temperature were obtained. By using a generic
      microchip containing all 4096 hexamer oligonucleotides, it has been determined
      that the dye has no distinct specificity to any certain motifs of the nucleotide
      sequence. Thus, ImD-310 may serve as an efficient fluorescent probe to quickly
      estimate the amount of oligonucleotides immobilized in a microchip, in an
      electrophoretic gel, etc.

PMID- 14714503
TI  - [Effect of Ca2+ ions on hydrodynamic properties of pentamer and decamer of C
      reactive protein in solution].
AB  - The molecular mass and sedimentation coefficient of native C-reactive protein in
      solution were determined by analytical ultracentrifugation in the presence and
      absence of calcium ions. Pentameric C-reactive protein was shown to be the major
      macroscopic form of this protein in solution. The removal of calcium ions from
      solution caused decompaction of the protein accompanied by changes in its
      hydrodynamic parameters. The sedimentation coefficient s20(0), w of pentameric C
      reactive protein in solution containing 2 mM--Ca2+ (6.6S) exceeded that for C
      reactive protein in solution containing 2 mM EDTA (6.4S). Analysis of average
      molecular masses Mw and Mz obtained from sedimentation data demonstrated that the
      solution of highly purified protein was not homogeneous. As shown by
      intermolecular crosslinking, the solution also contained the 241-kDa decamer of C
      reactive protein (9.5S) as a separate macroscopic form, whose share hardly
      reached 10% in the presence of 2 mM Ca2+ and increased after removal of calcium
      ions. The decamers were shown to result from intermolecular association of the
      pentamers.

PMID- 14714504
TI  - [Virions and membrane proteins of the potato X virus interact with microtubules
      and enables tubulin polymerization in vitro].
AB  - A study was made of the in vitro interactions of virions and the coat protein
      (CP) of the potato virus X (PVX) with microtubules (MT). Both virions and CP
      cosedimented with taxol-stabilized MT. In the presence of PVX CP, tubulin
      polymerized to produce structures resistant to chilling. Electron microscopy
      revealed the aberrant character of the resulting tubulin polymers (protofilaments
      and their sheets), which differed from MT assembled in the presence of cell MAP2.
      In contrast, PVX virions induced the assembly of morphologically normal MT
      sensitive to chilling. Virions were shown to compete with MAP2 for MT binding,
      suggesting an overlap for the MT sites interacting with MAP2 and with PVX
      virions. It was assumed that PVX virions interact with MT in vivo and that,
      consequently, cytoskeleton elements participate in intracellular
      compartmentalization of the PVX genome.

PMID- 14714505
TI  - [Brachial plexus palsy in adults with radicular lesions, general concepts,
      diagnostic approach and results ].
AB  - In post-traumatic brachial plexus lesions in adults, early repair will
      necessitate a variety of nerve grafting and nerve transfer procedures. In
      complete palsies, a graft is performed from a radicular stump, using intercostal
      nerve transfers, partial cross C7 transfer, and the distal spinal accessory
      nerve. This will provide elbow flexion and extension in 75% of cases, and
      shoulder abduction or rotation in 50% of cases. In the upper type palsies, ulnar
      biceps transfer is the standard procedure. Grafting from a ruptured cervical
      root, when available, is performed to reanimate the shoulder. In C5 C6 and C7
      palsies, extension of the wrist and fingers is provided by tendon transfers. In
      chronic palsies, elbow flexion and extension loss is treated by means of free
      muscle transfers, (latissimus dorsi or gracilis) combined with nerve transfers
      (intercostals or spinal accessory). Secondary procedures are routinely necessary
      following recovery of elbow flexion. For the shoulder-humeral shaft osteotomy or
      fusion, for the hand-cosmetic fusion of the wrist and distal radio-ulnar joint in
      the prone position, or palliative treatment in case of partial recovery. For such
      weak "plexic hands", we have developed a specific hierarchical functional scale,
      useful for surgical decisions.

PMID- 14714506
TI  - [Non-traumatic osteoarthritis of the wrist: chondrocalcinosis].
AB  - Post-traumatic arthritis of the wrist is a common disorder, mostly after scapho
      lunate or scaphoid injury. Some patients in our experience and in literature have
      no known trauma, are bilateral and have a mean age much higher than usual post
      traumatic cases. Radiological (during an often-extensive medical history) and
      biological studies of these patients led us to think there is a form of
      chondrocalcinosis of the wrist, with a four stages evolution, similar to SLAC and
      SNAC wrist but with often no scapho lunate gap, vertical embedding of the
      scaphoid in the radius and chalky incrustation of the joint. We called that form
      of dislocation of the carpus: scaphoid chondrocalcinosis advanced collapse or
      SCAC wrist. Surgical treatment of advanced cases is described. Scaphoidectomy and
      resection of triquetrum are performed, associated with hamato-luno-capitate
      fusion. Other rare forms are described and literature (mostly radiological and
      rheumatological because these patients are often been mistaken as SLAC wrist) is
      studied.

PMID- 14714507
TI  - [Occupational risk factors for radial tunnel syndrome in factory workers].
AB  - STUDY: The purpose of the study was to evaluate the professional and
      extraprofessional risk factors for radial tunnel syndrome (RTS) in employees of
      three large companies. METHOD: Twenty-one cases of RTS were compared to 21
      controls, matched for age, sex, and activity. In nine cases, RTS was associated
      with carpal tunnel syndrome. The analysis considered medical history,
      extraprofessional activity, and the ergonomic and organisational aspects of work.
      RESULTS: The study demonstrated three risk factors of RTS related to work
      conditions. The regular use of a force of at least 1 kg (OR = 9.1 (1.4-56.9))
      more than 10 times per hour is the main biomechanical risk factor. Static work
      (OR = 5.9 (1.2-29.9)) as well as work with the elbow constantly extended 0 degree
      to 45 degrees, is strongly associated with an increased risk of RTS (OR = 4.9
      (1.0-25.0)). Complete extension of the elbow associated with pronation and
      supination of the forearm may cause trauma to the radial nerve in the radial
      tunnel. On the other hand, we found no personal factors and no extraprofessional
      activities which were associated with an increased risk of RTS. CONCLUSIONS: This
      study shows that motions of the forearm requiring intense effort and performed
      with the elbow in extension and the forearm in pronation and supination increase
      the risk of RTS.

PMID- 14714508
TI  - [Treatment of phalangeal neck fractures in children: technical suggestion].
AB  - INTRODUCTION: Phalangeal neck fractures in children are not very frequent
      lesions. The purpose of this study is to bring out results of treatment of these
      fractures and provide an adequate procedure. PATIENTS AND METHODS: Twenty-three
      patients with 24 phalangeal neck fractures were reviewed. Seventeen boys and six
      girls with a mean age of 7 years and 6 months. Open wound fractures were noted in
      13 cases. A direct trauma was noted in 17 cases and an indirect trauma in seven
      cases. Treatment consisted of a closed reduction and cast immobilization in four
      cases. A closed reduction and percutaneous pinning in seven cases. Open reduction
      and osteosynthesis in 13 cases. RESULTS: All patients were reviewed with a mean
      follow-up of 16 months and functional results were evaluated by measuring the
      Total Active Motion. Fractures treated orthopedically (4) gave Good results;
      percutaneous pinning (seven cases) gave one Poor, one Fair and five Good results;
      open reduction and osteosynthesis gave zero Good, six Fair and seven Poor
      results. Phalangeal head osteonecrosis was noted in four cases treated by open
      reduction. DISCUSSION: Closed reduction and percutaneous treatment of these
      fractures give the best functional results. This study demonstrates that open
      surgical reduction of these fractures leads to phalangeal head osteonecrosis and
      poor functional result. We propose here a technical improvement of percutaneous
      reduction with intrafocal pining and osteosynthesis. CONCLUSION: This technical
      improvement of percutaneous reduction and pinning allow to combine the advantages
      of a closed reduction and to avoid distal epiphyseal necrosis.

PMID- 14714509
TI  - [Reinsertion of the flexor tendon using a suture anchor: prospective study using
      early active motion].
AB  - INTRODUCTION: The aim of this study was to evaluate subjective and functional
      results of a prospective continuous series of immediate tendon-to-bone repair of
      the F.D.L. using a miniaturized anchor. METHOD: Seven patients have been operated
      by the same surgeon in emergency for a section of the FDL in zone one. Distal
      tendon-to-bone re-attachment has been realized using a mini-G II Mitek anchor
      suture. Five of the patient were male, four of them being manual workers. Only
      one had a work accident. According to Leddy and Packer's classification one
      patient had a stage 1 lesion and the six others had stage two lesions. The
      injured fingers showed associated lesions in four cases. Rehabilitation consisted
      of early active mobilization protected by a Duran-type splint. All the patients
      had been examined by an independent surgeon at 10 months follow-up. Mean age at
      that time was 32 years. RESULTS: One patient was very satisfied with his results
      while the six others were satisfied. Two minor complications were encountered,
      one of them being directly in relation to the implant. Total Active Motion (TAM)
      summed up to 92% of the arch of motion of the normal controlateral finger. Pinch
      force reached 81% compared to that of the controlateral finger. Two patients
      described no pain. Mean eviction from work was 70 days. DISCUSSION: Tendon-to
      bone repair of the FDL using an anchor seems to give good results on pain, TAM
      and on force. The only complication due to the implant did not have any
      functional incidence. The series of Marin Braun on 77 cases of such repairs using
      a barb-wire show similar results compared to the implant used in our series.
      However, anchor sutures have several advantages compared to a transcutaneous
      device: they reduce the risk of infection, of nail dystrophy and they offer a
      better comfort to the patient.

PMID- 14714510
TI  - [A case report of desmoid tumor of the finger].
AB  - We report the case of a 20-year-old woman with a desmoid fibroma of the finger,
      which is an extremely rare location. Desmoid fibromas are benign but very
      infiltrative tumors, known for their frequent recurrences. Because of the many
      vascular and nervous structures concentrated in the finger, complete surgical
      excision is difficult.

PMID- 14714511
TI  - [Simultaneous trapezium and Bennett's fractures: a case report and review of the
      literature].
AB  - Combined Bennett's fracture and the body of the trapezium are rare. The authors
      report a case in which closed reduction and internal fixation were performed to
      stabilize these fractures. The result at 5-month follow-up was good in terms of
      range of motion and radiological aspect. A literature review and treatment
      methods are included.

PMID- 14714512
TI  - [Fenton's syndrome or scapho-capitate fracture (a case report)].
AB  - INTRODUCTION: Scapho-capitate fracture is a rare lesion and its mechanism is
      controversial. Forced extension seems to be the most frequent cause as this
      movement of the wrist induces scaphoid fracture by compression. Hyperextension of
      the wrist as a result of the scaphoid lesion, allows contact between the
      posterior margin of the radius and the neck of the capitate inducing a capitate
      fracture. MATERIALS AND METHODS: We report a case of Fenton's Syndrome, the
      patient was operated as an emergency by pining and immobilization of the carpus
      and thumb until bone consolidation had occurred. RESULTS: Consolidation was noted
      at 8 weeks with a good mobility of the wrist. DISCUSSION: Fenton's Syndrome is a
      rare lesion of the wrist. Analysis of our own case and a review of literature
      demonstrated extension as a causative mechanism, and the frequency of delayed
      diagnosis. Because of the presence of instability, scaphoid reduction and
      osteosynthesis is necessary. Immobilization of the carpus and thumb is essential
      until bony consolidation is obtained.

PMID- 14714513
TI  - [Lev Aleksandrovich Bliumenfel'd (23.IX.1921-3.IX.2002)].

PMID- 14714514
TI  - [L.A. Bliumenfeld and quantum conceptions in biophysics].
AB  - The development of quantum conceptions in biophysics and the role of experimental
      and theoretical works of L.A. Blumenfeld in this process were considered. The
      influence of his investigations on the researches of other scientists in the
      field of quantum biophysics was shown.

PMID- 14714515
TI  - [Statistical fluctuations in processes of gene expression regulation:
      consideration of the problem from point of view of statistical mechanics].
AB  - The regulation of gene expression is a basic problem of biology. In some cases,
      the gene activity is regulated by specific binding of regulatory proteins to DNA.
      In terms of statistical mechanics, this binding is described as the process of
      adsorption of ligands on the one-dimensional lattice and has a probability
      nature. As a random physical process, the adsorption of regulatory proteins on
      DNA introduces a noise to the regulation of gene activity. We derived equations,
      which make it possible to estimate this noise in the case of the binding of the
      lac repressor to the operator and showed that these estimates correspond to
      experimental data. Many ligands are able to bind nonspecifically to DNA.
      Nonspecific binding is characterized by a lesser equilibrium constant but a
      greater number of binding sites on the DNA, as compared with specific binding.
      Relations are presented, which enable one to estimate the probability of the
      binding of a ligand on a specific site and on nonspecific sites on DNA. The
      competition between specific and nonspecific binding of regulatory proteins plays
      a great role in the regulation of gene activity. Similar to the one-dimensional
      "lattice gas" of particles, ligands adsorbed on DNA produce "one-dimensional"
      pressure on proteins located at the termini of free regions of DNA. This
      pressure, an analog of osmotic pressure, may be of importance in processes
      leading to changes in chromatin structure and activation of gene expression.

PMID- 14714516
TI  - [DNA complexes, formed on aqueous phase surfaces: new planar polymeric and
      composite nanostructures].
AB  - The formation of DNA complexes with Langmuir monolayers of the cationic lipid
      octadecylamine (ODA) and the new amphiphilic polycation poly-4-vinylpyridine with
      16% of cetylpyridinium groups (PVP-16) on the surface of an aqueous solution of
      native DNA of low ionic strength was studied. Topographic images of Langmuir
      Blodgett films of DNA/ODA and DNA/PVP-16 complexes applied to micaceous
      substrates were investigated by the method of atomic force microscopy. It was
      found that films of the amphiphilic polycation have an ordered planar
      polycrystalline structure. The morphology of planar DNA complexes with the
      amphiphilic cation substantially depended on the incubation time and the phase
      state of the monolayer on the surface of the aqueous DNA solution. Complex
      structures and individual DNA molecules were observed on the surface of the
      amphiphilic monolayer. Along with quasi-linear individual bound DNA molecules,
      characteristic extended net-like structures and quasi-circular toroidal condensed
      conformations of planar DNA complexes were detected. Mono- and multilayer films
      of DNA/PVP-16 complexes were used as templates and nanoreactors for the synthesis
      of inorganic nanostructures via the binding of metal cations from the solution
      and subsequent generation of the inorganic phase. As a result, ultrathin
      polymeric composite films with integrated DNA building blocks and quasi-linear
      arrays of inorganic semiconductor (CdS) and iron oxide nanoparticles and
      nanowires were obtained. The nanostructures obtained were characterized by
      scanning probe microscopy and transmission electron microscopy techniques. The
      methods developed are promising for investigating the mechanisms of structural
      organization and transformation in DNA and polyelectrolyte complexes at the gas
      liquid interface and for the design of new extremely thin highly ordered planar
      polymeric and composite materials, films, and coatings with controlled
      ultrastructure for applications in nanoelectronics and nanobiotechnology.

PMID- 14714517
TI  - [Computer module design of the parametric structure of water].
AB  - The algorithms of module design and the results of constructing the parametric
      structures of water were considered. The tetrahedral electron structure of the
      oxygen atom of water, which is a double symmetric donor and acceptor of protons,
      was taken as the main postulate. As opposed to the crystal lattices of diamond
      and ice, the hexacycle twist-bath was considered as the basic element of the
      original structure. A great variety of possible structures were obtained, which
      involve quasi-unidimensional (helices, rods), dendrite-like, ring-shaped, planar,
      and fractal structures, as well as combinatoric structures composed of these
      forms. The functions of distribution of valence angles in fractal structures
      optimized with respect to energy have two main maxima at 104 and 112 degrees, as
      differentiated from the starting ideal tetrahedral angle of 109.5 degrees.
      Changes in, and the accumulation of elastic energy of distortions of rod
      structure of different symmetry were analyzed. This energy can be utilized during
      the conformational changes of biopolymers. The substantial difference in the
      solubility of two anomeric forms of glucose is explained by a different degree of
      conformity of the glucose molecule structure to the structure of bound water.

PMID- 14714518
TI  - [Heat-induced activation of reducing properties of of sea water].
AB  - It was shown using the Ellman's reagent that chloride and bicarbonate anions are
      the heat-induced reducing agents of sea-water, and their combined action is more
      than additive. Sulfate anions do not exhibit these properties. The influence of
      sea-water anions on the heat-induced production of hydrogen peroxide was studied
      by enhanced chemiluminescence in a peroxidase-luminol-p-iodophenol system. In
      NaCl and NaHCO3 solutions, at concentration and pH values equal to those of sea
      water, the production of H2O2 upon heating increased, as compared with water,
      whereas sulfate anions depressed its formation. By using coumarin-3-carboxylic
      acid as a fluorescent detector of OH radicals, a substantial increase in the
      production of radicals in the presence of chloride and bicarbonate anions upon
      heating was shown. The effect is due to the electron donor properties of these
      anions, which lead to the decomposition of H2O2 with the formation of OH
      radicals. The results obtained were considered from the viewpoint of the
      equivalence of heat and electromagnetic radiation of an absolutely black body. It
      is supposed that the high-energy quanta of its spectrum lead to the dissociation
      of anions with the formation of a hydrated electron and radicals. Then a
      recombination of radicals with the formation of various molecular products takes
      place.

PMID- 14714519
TI  - [Biophysical problems of oligopeptide regulation].
AB  - A number of physical problems arising in studies of the relationship between the
      structure and function of natural peptide molecules consisting of 2-50 amino acid
      residues were considered. Among these are the determination of functionally
      significant sizes of molecules and their configurations, a search for general
      principles of classification, and a study of the mechanisms of delivery of
      oligopeptide molecules and their binding to receptor structures. The natural
      concentrations and coefficients of diffusion of oligopeptides were compared with
      the time of their real functioning. The solubility of these and other problems
      was assessed.

PMID- 14714520
TI  - [A simple model of molecular construction].
AB  - The microscopic model illustrating the ideas of L.A. Blumenfeld about the role of
      slow conformational relaxation in the mechanism of action of enzymes is
      discussed.

PMID- 14714521
TI  - [Electrogenic reactions in cytochrome bf-complexes in a model system].
AB  - By using the direct electrometric technique, the flash-induced generation of the
      difference in electrical potentials in hybrid proteoliposomes containing
      photosystem 1 and cytochrome bf complexes from cyanobacteria Synechocystis sp.
      PCC 6803 was studied. It was shown that the primary donor P700 in photosystem I
      and cytochrome f are predominantly localized near the outer surface of the
      proteoliposomal membrane, which made it possible to study for the first time
      electrogenic reactions of cytochrome bf complexes in a model system. In the
      presence of decyl plastoquinol and cytochrome c6, besides the fast electrogenic
      phase determined by the separation of charges in photosystem I, additional
      electrogenic phases in the submillisecond and millisecond ranges were observed.
      These phases were partially depressed in the presence of the inhibitor of the
      plastoquinone reductase site NQNO and fully disappeared after the addition of the
      inhibitor of the plastoquinol oxidase site stigmatellin. A possible mechanism of
      the electrogenic reactions in cytochrome bf complexes was considered.

PMID- 14714522
TI  - [Electrostatic interactions in catalytic centers of F1-ATPase].
AB  - The first part of this paper is a brief review of works concerned with the
      mechanisms of functioning of F0F1-ATP synthases. F0F1-ATP syntheses operate as
      rotating molecular machines that provide the synthesis of ATP from ADP and
      inorganic phosphate (Pi) in mitochondria, chloroplasts, and bacteria at the
      expense of the energy of electrochemical gradient of hydrogen ions generated
      across energy-transducing mitochondrial, chloroplast or, bacterial membranes. A
      distinguishing feature of these enzymes is that they operate as rotary molecular
      motors. In the second part of the work, we calculated the contribution of
      electrostatic interactions between charged groups of a substrate (MgATP),
      reaction products (MgADP and Pi), and charged amino acid residues of the F1
      ATPase molecule to energy changes associated with the binding of ATP and its
      chemical transformations in the catalytic centers located at the interface of the
      alpha- and beta-subunits of the enzyme (oligomer complex alpha 3 beta 3 gamma of
      bovine mitochondrial ATPase). The catalytic cycle of ATP hydrolysis considered in
      the work includes conformational changes of alpha- and beta-subunits caused by
      unidirectional rotations of the central gamma-subunit. The results of our
      calculations are consistent with the idea that the energetically favorable
      process of ATP binding to the "open" catalytic center of F1-ATPase initiates the
      rotation of the gamma-subunit followed by ATP hydrolysis in another ("closed")
      catalytic center of the enzyme.

PMID- 14714523
TI  - [Molecular nature of regulating cell division and differentiation in an
      organism].
AB  - A short review of the investigations of contactins, tissue-specific compounds
      providing intercellular contacts, which were discovered by the authors in the
      60s, is presented.

PMID- 14714525
TI  - [Phallotoxins as an instrument for studying the intramyofibrillar regulation of
      muscle contraction].
AB  - The contraction of myofibrils is regulated by the coordinated action of Ca2+ and
      myosin cross-bridges. Phallotoxins induce a variety of specific changes in
      myofibrillar functioning and are therefore a potentially valuable tool for muscle
      research. There are two greatly differing classes of drugs among phallotoxins:
      (1) recently discovered secophalloidin and its derivatives. The unique property
      of secophalloidin is muscle activation without Ca2+, possibly by direct influence
      on actomyosin interaction. These drugs seem to be especially useful for studying
      the role of cross-bridges in muscle regulation; (2) the phalloidin group, which
      includes the majority of phallotoxins. When binding to the phalloidin site on F
      actin, they cause muscle-specific changes. In cardiac muscle they work as Ca2+
      sensitizers, increasing both the maximal force and Ca2+ sensitivity. An advantage
      of these drugs is that the target site is known, which allows one to unravel the
      sequence of molecular events leading to increased contractile function.
      Presumably, the complex effect of phalloidin in skeletal muscle is related to the
      disturbance of the actin-nebulin interaction, which may help to clarify the role
      of nebulin in the regulation contraction.

PMID- 14714524
TI  - [Analysis of mechanism of work of mitochondrial adenine nucleotide translocase
      using mathematical models].
AB  - The kinetics of exchange of adenine nucleotides in a system with reconstituted
      mitochondrial adenine nucleotide translocase (ANT) was simulated mathematically
      to analyze the basic mechanisms of ANT functioning. Two known alternative kinetic
      schemes were analyzed, the ping-pong type scheme with single-center substrate
      binding and the scheme of sequential two-center substrate binding at opposite
      sides of ANT. According to our modeling, both schemes can explain the
      experimental data on the adenine nucleotide exchange in the reconstituted ANT
      system. However, the characteristic kinetic pattern of ADP exchanges in the mono
      exchange mode was reproduced only by the sequential binding scheme. This scheme
      is consistent with the data on the tetrameric structure of ANT. On the other
      hand, only the single-center binding scheme was compatible with recent data on
      possible translocation of ATP and ADP by the carrier that has no bound adenine
      nucleotide on its opposite side. Based on the analysis of the literature data on
      ANT properties, a compromise scheme of ANT operation was proposed. In the
      framework of this scheme, the ANT dimers function by the single-center binding
      mechanism: however, in tetramers they are integrated into a substructure with two
      oppositely oriented binding centers working by the mechanism of sequential
      substrate binding. Labile bonds between the ANT-forming dimers could allow
      conformational rearrangements of ANT induced by various influences on
      mitochondrial membrane structure, including those leading to the induction of
      permeability transition pores in apoptosis.

PMID- 14714526
TI  - [Reaction of rats organ cells to inhibition of protein biosynthesis by sublethal
      doses of cycloheximide].
AB  - Time-dependent responses of cellular systems in rat organs and Fe(3+)-transferrin
      and Cu(2+)-ceruloplasmin pools in blood to the blocking of translation by
      sublethal doses of cycloheximide (CHI) was studied by EPR spectroscopy and
      radioisotope techniques. It was shown that, within the early post-CHI-treatment
      time, the suppression of deoxyribonucleotide and DNA biosynthesis, the activation
      of catabolic enzymes, the inhibition of electron transfer in the mitochondrial
      electron transport chain, the activation and the following inactivation of
      cytochrome P-450, and an intensive production of nitrosyl complexes in rat blood
      and organs occur. In addition, the activation of the synthesis of steroid
      hormones in adrenal gland was revealed within 1-24 h after cycloheximide
      injection. In response to these metabolic disturbances, nonspecific compensatory
      recovery reactions developed, first of all, the "reprograming" of the translation
      process to produce new protein-synthesizing elements instead of cycloheximide
      blocked ones. The activation of protein synthesis promotes the recovery of
      deoxyribonucleotide and DNA synthesis, the restoration of the redox state of
      mitochondrial and microsomal electron transport chains in organs as well as an
      increase of Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in rat blood. These
      metabolic processes result in the full recovery of the functional ability of
      organs.

PMID- 14714527
TI  - [Luminescent indicators in various parts of wheat leaves in ontogenesis].
AB  - A comparative study of slow fluorescence induction, fluorescence spectra,
      thermoluminescence, photosynthetic activity and chlorophyll content in
      ontogenesis of wheat seedlings (Triticum aestivum L, cv. Yubileinayd) grown in
      the laboratory conditions was carried out. It was shown that (FM-FT)/FT values of
      slow fluorescence induction increased with the age of leaf part, reached a
      maximum (for 2-week-old seedlings), and then decreased. Changes in (FM-FT)/FT
      positively correlated with the changes in photosynthetic activity per chlorophyll
      unit (delta O2/(delta t.chlorophyll)); the coefficient of correlation r = 0.84, p
      > 0.999. The F685/F730 ratio of the intensities of fluorescence spectrum
      decreased with the increase in chlorophyll content. The relative light sum
      SA/S(tot) of band A of thermoluminescence changed in the same direction as delta
      O2/(delta t-chlorophyll), the relative light sum (SC/S(tot) of band C of
      thermoluminescence decreased during leaf maturation. The regularities revealed in
      the experiments are discussed in terms of changes in the structural and
      functional organization of the photosynthetic apparatus known from the
      literature.

PMID- 14714528
TI  - [Tunneling of autowaves through unexcitable parts of active media].
AB  - The mechanisms of propagation of autowaves through local heterogeneities in
      active media were studied by computer simulation. The model proposed by
      Zel'dovich and Frank-Kamenetsky and that of FitzHugh-Nagumo were used for
      studying autowave tunneling. It was shown that the underbarrier passage of an
      autowave through a nonexcitable area is limited by threshold values. It was shown
      that, for every fixed parameter value corresponding to the degree of
      nonexcitability of a local area, there exists a critical value for nonexcitable
      zone latitude. An autowave overcomes the barrier and continues to propagate when
      the value of zone latitude is less than the critical. Critical conditions for the
      origination of sources of secondary periodical sequences of impulses in excitable
      medium were found. It was shown that the properties of sources of secondary
      autowaves can be modified by regulating the size of the nonexcitable zone and the
      zone of increased excitability. In particular, the conditions were explored under
      which spatial irregularity behaves as a source of a unidirectional and/or an
      asynchronous sequence of impulses.

PMID- 14714529
TI  - [Dependence of 'macroscopic fluctuations" on geographic coordinates (from
      materials of Arctic (2000) and Antarctic (2001) expeditions].
AB  - The detailed structure of histograms constructed from the results of synchronous
      measurements of the alpha-activity of 239Pu microsamples, conducted in Pushchino
      (Moscow Region, Russia) and on board the ship "Academician Fedorov" during the
      Arctic and Antarctic expeditions (2000 and 2001) was analyzed. It was shown that,
      if the histograms were constructed over a total period of 15 min and more, the
      "local zone effect" and the circadian periodicity in the similarity of histogram
      structure, observed during measurements in Pushchino, are not found in
      measurements on board the ship near the North Pole (latitude 82 degrees). If the
      histograms were constructed over a total time of 1 min, a strict periodicity
      ("stellar day" 23 h 56 min) in the appearance of similar histograms in Pushchino
      and the Arctic and a strict synchronicity of the appearance of similar histograms
      of measurements in Pushchino and on board the ship at the same local geographical
      time were observed. During the Antarctic expedition, the effect of synchronicity
      of the appearance of similar histograms in Pushchino and on board the ship
      decreased as the ship moved towards the South Pole and the difference in latitude
      between the points of measurements increased.

PMID- 14714530
TI  - [Macroscopic fluctuations: periodicity of the manifestation of "near-zone"
      effect].
AB  - The "near-zone effect" one of the main manifestations of the phenomenon of
      macroscopic fluctuations, was further investigated. It was shown that the
      statistical significance of the near-zone effect varies with time with a period
      of about 3.5 days. A phenomenological model was proposed to describe the results
      obtained.

PMID- 14714531
TI  - [Surface of the Pacific Ocean and physical mechanisms of prebiological
      evolution].
AB  - The hypothesis about the spontaneous generation of living cell predecessors on
      the ocean surface during prebiological evolution is further developed. Data
      obtained in experiments and observations are given that support our point of
      view. It is shown that the physicochemical properties of the nonequilibrium ocean
      atmosphere boundary including ionic asymmetry, fractionation of enantiomers of
      amino and nucleic acids, and the formation of sealed vesicles provide conditions
      under which the spontaneous generation seems quite possible.

PMID- 14714532
TI  - ["Unpredictablity of the quantum world" and logical catastrophe].
AB  - The fundamental gnoseological question that is always present in a basic science
      is: Can this science adequately predict the future? In classical mechanics, we
      deal in many cases with dynamic chaos; therefore, this prediction is most often
      impossible. In the quantum theory, the dynamic chaos associated with the
      disturbances of initial conditions is formally absent. Nevertheless, as it was
      shown in this work, there are other reasons that directly relate to what is
      called the paradoxes of formal logic, which, in the case of quantum theory, too,
      do not enable one to precisely determine what will happen in the future.

PMID- 14714533
TI  - Pediatric lung transplantation: update 2003.
AB  - In the past 15 years there have been more than 1200 pediatric lung and heart-lung
      transplants worldwide. This article regarding the current status of pediatric
      lung transplantation describes indications, outcomes, and complications, with
      particular emphasis on issues specific to pediatrics, including growth.
      Information useful to the pediatrician and pediatric pulmonologist is also
      included. Issues important to the future are reviewed.

PMID- 14714534
TI  - Phosphoprotein isotope-coded solid-phase tag approach for enrichment and
      quantitative analysis of phosphopeptides from complex mixtures.
AB  - Many cellular processes are regulated by reversible protein phosphorylation, and
      the ability to broadly identify and quantify phosphoproteins from proteomes would
      provide a basis for gaining a better understanding of these dynamic cellular
      processes. However, such a sensitive, efficient, and global method capable of
      addressing the phosphoproteome has yet to be developed. Here we describe an
      improved stable-isotope labeling method using a phosphoprotein isotope-coded
      solid-phase tag (PhIST) for isolating and measuring the relative abundances of
      phosphorylated peptides from complex peptide mixtures resulting from the
      enzymatic digestion of extracted proteins. The PhIST approach is an extension of
      the previously reported phosphoprotein isotope-coded affinity tag (PhIAT)
      approach developed by our laboratory, where phosphoseryl and phosphothreonyl
      residues were derivatized by hydroxide ion-mediated beta-elimination followed by
      the Michael addition of 1,2-ethanedithiol (EDT). Instead of using the biotin
      affinity tag, peptides containing the EDT moiety were captured and labeled in one
      step using isotope-coded solid-phase reagents containing either light (12C6, 14N)
      or heavy (13C6, 15N) stable isotopes. The captured peptides labeled with the
      isotope-coded tags were released from the solid-phase support by UV photocleavage
      and analyzed by capillary liquid chromatography-tandem mass spectrometry. The
      efficiency and sensitivity of the PhIST labeling approach for identification of
      phosphopeptides from mixtures were determined using casein proteins. Its utility
      for proteomic applications was demonstrated by the labeling of soluble
      phosphoproteins from a human breast cancer cell line.

PMID- 14714535
TI  - [Intracerebral hemorrhage following chronic subdural hematoma evacuation: report
      of two cases ].

PMID- 14714536
TI  - English for the medical profession. How do we support learners?

PMID- 14714537
TI  - Differential roles of estrogen receptor alpha and beta in the regulation of
      neuroendocrine functions and socio-sexual behaviors.

PMID- 14714538
TI  - Dynamic neck muscle training of relaxation does not improve chronic neck pain.

PMID- 14714539
TI  - Community-based rehabilitation improves function of patients with traumatic brain
      injury.

PMID- 14714540
TI  - Treadmill training and/or body weight support may not improve walking ability
      following stroke.

PMID- 14714541
TI  - Bilateral facial paralysis: what's the cause?

PMID- 14714542
TI  - Plant-associated microorganisms: a view from the scope of microbiology.

PMID- 14714543
TI  - An affordable antimalarial.

PMID- 14714544
TI  - Tidal turbines: wave of the future?

PMID- 14714545
TI  - Colombia defies court on coca.

PMID- 14714546
TI  - Funky chicken: consumers exposed to arsenic in poultry.

PMID- 14714547
TI  - Poisoning young minds? Methyl parathion may be linked to neurodevelopment
      problems.

PMID- 14714548
TI  - Do-it-yourself biospecimens: the benefits of home collection.

PMID- 14714549
TI  - [Trafficking of NMDA receptors and its implications for synaptic function].

PMID- 14714550
TI  - Possible involvement of epidermodysplasia verruciformis human papillomaviruses in
      the immunopathogenesis of psoriasis: a proposed hypothesis.
AB  - We have shown previously in psoriasis a very high prevalence of epidermodysplasia
      verruciforms-associated human papillomavirus 5 (EVHPV5) DNA and antibodies to
      human papillomavirus 5 (HPV5) virus-like particle (VLP) L1, and we suggested that
      this benign hyperproliferative disorder could be a reservoir for EVHPVs. Here we
      provide new data confirming the expression of EVHPVs in psoriasis and present our
      hypothesis on their possible involvement in the immunopathogenesis of the
      disorder. The new important finding was detection by radioimmunoprecipitation
      assay of a very high prevalence of antibodies to E6/E7 HPV5 oncoproteins, known
      to enhance keratinocyte proliferation. More recently, EV genes were identified,
      EVER1 and EVER2, whose mutations are responsible for epidermodysplasia
      verruciformis. Eidermodysplasia verruciforms-associated human papillomaviruses
      are harmless to the general population as a result of genetic restriction, which
      in psoriasis appears to be partly alleviated, and this may allow the viral gene
      expression. We hypothesize that induction of keratinocyte proliferation in
      psoriasis by various stimuli initiates the EVHPV life cycle with expression of
      early (E6/E7) and late (L1) viral proteins. The early proteins may, in turn,
      enhance the keratinocyte proliferation, and the late proteins could serve as
      target for specific-B- and T-cell-mediated responses. Immune responses against
      the viral antigens in the epidermis may result in the chemoattraction of
      leukocytes and Munro abscess formation, as well as in production of the psoriatic
      process. The novel immunomodulatory therapies could also inhibit immune responses
      against EVHPV proteins, leading to decreased cytokine production, keratinocyte
      proliferation and EVHPV expression. Thus the beneficial effect of these therapies
      is not discordant with the propose hypothesis of possible involvement of EVHPVs
      in the immunopathogenesis of psoriasis.

PMID- 14714551
TI  - The differential effect of broad band vs narrow band UVB with respect to
      photodamage and cutaneous inflammation.
AB  - Since Fischer reported on the superiority of 313 nm UVB compared with broad band
      UVB in the treatment of psoriasis, narrow band UVB has become the main
      phototherapeutical modality in several countries. There is some discussion about
      the safety and photobiological effects of narrow band UVB. In the present study,
      narrow and broad band UVB have been compared with respect to parameters for
      photodamage and inflammation. Fourteen healthy volunteers were randomized in two
      groups. Both groups were irradiated with three minimal erythema doses (MED) of
      narrow or broad brand UVB, respectively. Before and 4, 24 and 48 h after
      irradiation, 6 mm biopsies were taken from immunohistochemical analysis of p53,
      apoptosis and p16 (photodamage parameters) and T-cells, polymorphonuclear
      leukocytes (PMN) and Langerhans' cells (inflammatory cells). Mean MED for narrow
      band UVB was 8.125 times higher than broad band UVB. Significant changes in
      expression were seen for all parameters except for p16. P53, apoptosis, T-cells
      and PMN increased, while Langerhans' cell count decreased significantly. No
      significant differences were seen between the narrow band UVB. In conclusion,
      following irradiation of three MED narrow band UVB and broad band UVB safety
      parameters for carcinogenesis and inflammation were induced to the same extent.
      As narrow band UVB is more effective than broad band UVB, the present study
      suggests superiority of narrow band UVB as a treatment with a better benefit risk
      ration.

PMID- 14714552
TI  - Acute cutaneous barrier disruption activates epidermal p44/42 and p38 mitogen
      activated protein kinases in human and hairless guinea pig skin.
AB  - Acute cutaneous barrier disruption of the skin elicits various homeostatic repair
      responses in the epidermis. Although several candidates for the signaling
      mechanisms that induce these responses have been reported, e.g. the calcium and
      ion concentration, peroxisome proliferator-activated receptor-alpha, and TNF
      alpha signaling mediated by sphingomyelinases, the exact nature of the signals
      remains undertermined. Therefore, assuming that an important group of
      serine/threonine-signaling kinases, mitogen- and SAPK/JNK, might link the barrier
      disruption to the subsequent homeostatic responses, the activation of three MAPKs
      in hairless guinea pig or in human skin after barrier disruption was
      investigated. The epidermal barrier was insulated with tape stripping or organic
      solvents, and Western blotting, and immune complex kinase assay. In the skin of
      hairless guinea pigs, p44/42 MAPK and p38 MAPK, but nor SAPK/JNK, were continued
      to be activated for at least 180 min. The activation of p44/42 which positively
      correlated with the number of tape strippings, whereas K+ sucrose solution
      suppressed its activation. The activation of p44/42 MAPK was also induced by
      treatment of the skin with organic solvents. In similar fashion, p44/42 and p38
      MAPKs were found to be activated in human skin after tape stripping. These
      results for strongly suggest that the activation of p44/42 and p38 MAPKs links
      the stimuli of barrier disruption to the subsequent homeostatic responses to
      repair the barrier defect.

PMID- 14714553
TI  - Immunomolecular mapping of adherens junction and desmosomal components in normal
      human epidermis.
AB  - Adherens junctions (AJs) are cell-cell and cell-matrix junctions that are known
      to comprise the transmembrane and cytoplasmic components linked to the f-actin
      cytoskeleton. Although the presence of AJs han been confirmed in normal human
      epidermis, previous studies immunolocalizing AJ-related antigens have been
      controversial. The purpose of this study was to produce a more precise molecular
      mapping of AJs and their constituents in relation to desmosomes in normal human
      epidermal keratinocytes. Using an electron microscope (EM) method to optimally
      fix plasma membranes. AJ structures were typically seen as a narrowing of the
      intercellular space between two keratinocytes that was distinct from desmosomes
      and gap junctions. Such structures were consistently found more frequently in the
      upper epidermis than in the basal layer. Immunogold electron microscopy showed an
      absence of the AJ components (E-cadherin and beta-catenin) from desmosomal areas
      but they were present at interdesmosomal areas at sites of close membrane
      association. Conversely, the desmosomal components plakoglobin and plakophilin 1
      were restricted only to the outer attachment plaque of the desmosome. These
      results further confirm that AJs have a distinct molecular composition and
      distribution from desmosomes and that they regularly occur between desmosomes
      along the keratinocyte plasma membrane to provide alternative cell-cell adhesion
      mechanisms.

PMID- 14714554
TI  - Calcium triggers beta-defensin (hBD-2 and hBD-3) and chemokine macrophage
      inflammatory protein-3 alpha (MIP-3alpha/CCL20) expression in monolayers of
      activated human keratinocytes.
AB  - The inducible epidermal beta-defensins and the chemokine macrophage inflammatory
      protein-3alpha (MIP-3alpha/CCL20) are important mediators involved in innate and
      adaptive immunity and in the recruitment of immune cells. The aim of our study
      was to determine whether calcium could trigger the induction of beta-defensins
      (hBD-2 and hBD-3) mRNA and the release of MIP-3alpha by normal human keratinocyte
      monolayers. Epidermal cells derived from foreskin were cultured in defined medium
      supplemented with different calcium levels (0.09, 0.8 and 1.7 mM) and were
      stimulated or not with the pro-inflammatory cytokines tumor necrosis factor-alpha
      (TNF-alpha 1-500 ng/ml) or interferon-gamma (INF-gamma 1-100 ng/ml). A high
      calcium concentration (1.7 mM) alone applied in culture medium for 4 days was
      sufficient to induce hBD-2 and hBD-3 mRNA expression. Whatever interindividual
      variability in the expression of hBD-2 and hBD-3 mRNA and MIP-3alpha secretion,
      the addition of TNF-alpha for a short duration (26h), initiated a dose-dependent
      and coordinated up-regulation of hBD-2 and hBD-3 mRNA and MIP-3alpha release in
      keratinocyte cultures. Unlike hBD-2 and hBD-3 mRNA was preferentially stimulated
      by IFN-gamma rather than TNF-alpha. In our experimental conditions, L-isoleucine,
      described to stimulate beta-defensin in bovine epithelial cells, did not exert
      any effect either on hBD-2 and hBD-3 transcripts or MIP-3alpha protein. Taken
      together, these results confirm the major role of the maturation/differentiation
      process of normal human keratinocytes in the induction of inducible beta
      defensins and MIP-3alpha chemokine, which contribute in vivo to the
      immunosurveillance of the skin barrier function.

PMID- 14714555
TI  - Identification of differentially expressed genes in models of melanoma
      progression by cDNA array analysis: SPARC, MIF and a novel cathepsin protease
      characterize aggressive phenotypes.
AB  - Currently, the scale and consistency of changes of gene expression profiles in
      models of melanoma progression are largely unknown. Therefore, we investigated
      siblings of cell lines or malignant melanomas (MM), which have been selected by
      nude mouse passages for (a). increased tumorigenicity (local ECM-independent
      growth), (b). metastatic potential, or (c). selected for increase invasiveness
      using the Boyden chamber. cDNA array analysis surveying more than 27.000
      transcripts per cell line showed that 1.5-2.8% of all detectable transcripts were
      consistently differentially regulated during selection process in those models.
      Using array analysis, we identified 33 individual transcripts that exhibited
      significant differential hybridization paralleling the increased aggressiveness
      of the selected progeny. Because some of those genes could play a significant
      functional role in the progression of MM, we additionally proved their regulative
      pattern using Northern blotting. Among others, progressive overexpression of
      osteonectin/SPARC, a angiogenesis, was found in the selected offspring from all
      three experimental models and may therefore be considered as a potential marker
      for aggressive MM as well a promising therapeutic target. We further show that
      the selection of MM cells for increased ECM-independent local growth was
      accompanied by overexpresssion of macrophage migration inhibiting factor (MIF),
      an important modulator of both cell cycle progression and angiogenesis, and
      cathepsin Z, a novel member of the family of matrix degrading proteinases.

PMID- 14714556
TI  - Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF
      alpha polymorphism at position--308.
AB  - The mechanisms underlying induction of UVB-induced immunosuppression are not
      fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to
      play a central role. A single base pair polymorphism at position --308 in the
      promoter region of the TNF-alpha gene associated with an enhanced secretion of
      TNF-alpha has been identified in humans. We have therefore investigated the
      association of the --308 polymorphism with the risk of basal cell carcinoma (BCC)
      in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with
      a previous BCC (n=191) and health adults (n-107) were compared. For the TNF--308
      polymorphism there was significant association between the genotype or allele
      frequencies and having BCC. To determine whether patients with a previous BCC had
      an increased capacity to secrete TNF-alpha, mononuclear cells were stimulated
      with lipopolysaccharide. Mononuclear cells from patients with a previous BCC
      (n=15) demonstrated a significantly increased release of TNF-alpha upon
      stimulation with lipopolysaccharide (P<0.03) compared with mononuclear cells age
      matched control subjects (n=16). Further studies of other polymorphisms of the
      TNF-alpha gene associated with increased TNF-alpha production and BCC and
      necessary.

PMID- 14714557
TI  - Increased E-selectin, IL-8 and IL-10 gene expression in human skin after minimal
      trauma.
AB  - While clinical observations suggest that trauma to the skin plays a critical role
      in the induction of skin lesions in some skin diseases, the mechanism by which
      these lesions are induced is not known. We have postulated that minor trauma to
      the skin may lead to the expression of critical adhesion molecules on epidermal
      endothelial cells (E-selectin) and pro-inflammatory cytokines, which would
      predispose these areas to the development of skin lesions. In order to test this
      hypothesis normal inner arm skin of 11 normal subjects was gently rubbed with a
      pencil eraser for 2 min. Four hours after rubbing, skin biopsies were obtained
      from the rubbed site and from adjacent normal, unrubbed inner arm skin.
      Expression of E-selectin, intercellular adhesion molecules (ICAM-1) and the mRNA
      of selected cytokines was studied utilizing real time polymerase chain reactions.
      Biopsies were also examined for the presence of an inflammatory infiltrate and
      for the presence of E-selectin and ICAM-1. No clinical or histologic changes were
      seen in the skin expression/unrubbed skin expression = 9.0; (median ratio rubbed
      skin expression/unrubbed skin expression range 0.9-161.0), ICAM-1 (median rubbed
      skin expression/unrubbed skin expression = 3.2; range 0.9-19.8), IL-8 (median
      rubbed skin expression/unrubbed skin expression = 6.6; range 2.6-57.3) and IL-10
      (median rubbed skin expression/unrubbed skin expression = 13.1; range 2.4-29.0)
      was noted. Immunohistochemistry revealed the presence of E-selectin in the dermal
      blood vessels in three of four subjects 4 h after rubbing but not in the unrubbed
      skin. Changes in ICAM -1 or HLA-DR deposits were seen in the rubbed compared with
      the unrubbed skin. These findings demonstrated that minor trauma to skin may
      induce expression of E-selectin, ICAM-1 and IL-8, which may make the skin a more
      permissive site for the development of inflammatory reactions. These findings may
      play an important role in the development of skin lesions in areas of minor
      trauma.

PMID- 14714558
TI  - Histological evaluation of the effects of angiotensin peptides on wound repair in
      diabetic mice.
AB  - Recent studies have shown that angiotensin peptides accelerate dermal repair.
      Histological observation of samples taken at the termination of studies showed
      that the wounds treated with peptides were mature and organized by day 25 after
      full thickness excision in diabetic mice. However, the mechanisms by which this
      acceleration occurs has not been determined. In the experiments described here,
      the effect of angiotensin peptides (AII, A(1-7) and NorLeu (3)-A(1-7) on the
      quality of the healing wound was evaluated histologically. Administration of the
      peptides accelerated collagen deposition, re-epithelialization and new blood
      vessels formation. By day 4, the percentage of the wound with collagen increased
      two- to six-fold depending upon the peptide. The increase by angiotensin peptides
      continued throughout the experimental period. On days 4 and 7 9 (only) after
      injury, exposure to angiotensin peptides increased the number of blood vessels at
      wound site two-to three-fold. Finally, the percentage of the wound site covered
      with new epithelium increased after administration of angiotensin peptides. Re
      epithelialization was observed as early as day 4 in wounds treated ith
      angiotensin peptides. The increase was greater at later time points (up to 8-fold
      ar day 14 with NorLeu(3)-A(1-7) had an increase in neutrophils and macrophages on
      day 4 after wounding. Overall, administration of these peptides resulted in a
      healing site that was more mature, including reorganization of the collagen into
      a basket-weave appearance. Further, these studies confirm the superiority of
      NorLeu(3)-A(1-7) to AII and A(1-7) in wound healing evaluated at a microscopic
      level.

PMID- 14714559
TI  - In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal
      cells.
AB  - In vitro studies with human cell lines have demonstrated that the death receptor
      Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the
      present study was to investigate the relation between Fas expression and
      apoptosis as well as clustering of Fas in human epidermis after a single dose of
      UVB irradiation. Normal healthy individuals were irradiated with three minimal
      erythema doses (MED) of UVB on forearm or buttock skin. Suction blisters from
      unirradiated and irradiated skin were raised, and Fas, FasL, and apoptosis of
      epidermal cells quantified by flow cytometry. Clustering of Fas was from skin
      biopsied. Soluble FasL in suction blister fluid was quantified by ELISA. Flow
      cytometric analysis demonstrated increased expression intensity of Fas after
      irradiation, with 1.6-,2.2- and 2.7-fold increased median expression at 24, 48
      and 72 h after irradiation, respectively (n=4). Apoptosis was demonstrated by the
      TUNEL reaction, and the maximum of apoptotic cells was detected at 48 h after
      irradiation. Double-staining of Fas and TUNEL showed that apoptosis was
      restricted to the Fas-positive epidermal subpopulation, but there was no
      correlation between the intensities of Fas expression and TUNEL reaction. Median
      expression intensity of FasL-positive cells transiently decreased to 0.9- and 0.8
      fold of the preirradiation respective level after 24 h and 48 h, respectively,
      and returned to the respective preirradiation level at 72 h after irradiation
      (n=4). Concentrations of soluble FasL in suction blister fluid from UVB
      irradiated skin did not differ from those in unirradiated skin (n=5). Confocal
      laser scanning microscopy showed a rapid clustering of Fas within 30 min after
      irradiation. A simultaneous clustering of the adapter signalling protein FADD
      suggested that Fas clustering has a functional significance. Our results ar in
      accordance with previous findings from in vitro studies, and suggest that Fas is
      activated in vivo in human epidermis after UVB exposure.

PMID- 14714560
TI  - [Death on the operating table. Anesthesiologic and medicolegal aspects].
AB  - Since death on the operating table is a relatively rare incident, it raises a
      number of special medicolegal questions that are discussed in this article. One
      of the major concerns for medical personnel is being accused of malpractice
      during treatment, as it is an obvious presumption on the part of laymen that
      death was directly related to the medical treatment as compared with other in
      hospital deaths. Questions such as who is responsible for issues of informed
      consent and liability are discussed. Other important aspects such as
      communication with the bereaved, transparent chronological documentation of the
      death circumstances, questions regarding certification of death, questions
      arising from autopsy done to determine the reason of death, questions about
      malpractice, legal requirements concerning confidential medical communication and
      information about what must be sent to the professional indemnity insurance
      company are elucidated. There is also some special information presented for
      cases that involve the deaths of Jehovah's Witnesses.

PMID- 14714561
TI  - Evaluation of combined gene regulatory elements for transcriptional targeting of
      suicide gene expression to malignant melanoma.
AB  - Selective killing of tumors can be achieved by targeting the transcription of
      suicide genes via specific DNA control elements to malignant cells. Three
      different enhancer-promoter systems were constructed and evaluated for their
      capability to direct gene expression to melanoma. Two tissue-specific (tyrosine
      and MIA) promoters and one weak viral promoter were fused to multiple tandem
      copies of a melanocyte-specific enhancer element. Reporter gene assays revealed a
      maximum increase in transcription by combining each promoter with 3-4 copies of
      the enhancer and demonstrated that all enhancer-promoter combinations exhibited
      tissue-specific activity. Though this activity was still significantly less than
      that of the strong but unspecific cytomegalovirus (CMV) promoter. In contrast,
      when those combinations were employed to drive the expression of two suicide
      genes, encoding the diptheria toxin A chain (DT-A) and the prodrug-activating
      herpes simplex virus thymidine kinase (TK), respectively, only those constructs
      in which transcription was under control of tissue-specific promoter elements
      mediated selective killing of melanoma cells. This killing was in the range of
      cell death induced by CMV promoter activity. Our data indicate that the
      enhancer/tyrosinase and enhancer/MIA promoter constructs but not the viral
      promoter constructs can provide a valuable tool for selective suicide gene
      expression in melanoma.

PMID- 14714562
TI  - Protein kinase C isozymes regulate proliferation and high cell density-mediated
      differentiation in HaCaT keratinocytes.
AB  - Protein kinase C (PKC) isoforms play pivotal roles in the regulation of
      differentiation of normal human epidermal keratinocytes (NHEK). In this study, we
      investigated the participation of the PKC system in the proliferation and high
      cell density-induced differentiation of the human immortalized keratinocyte line
      HaCaT. HaCaT keratinocytes possessed a characteristic PKC isoform pattern (PKC
      alpha, beta, gamma, delta, epsilon, eta, theta, zeta), which altered during
      proliferation and differentiation. The GF109203X compound, a selective PKC
      inhibitor, suppressed the expressions of the lat (granular cell) differentiation
      markers involucrin (INV) and filaggrin (FIL), and the terminal marker
      keratinocyte-specific transglutaminase-1 (TG), but did not affect the level of
      the early (spinous cell) marker keratin 10 (K10) and cellular proliferation.
      Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, inhibited
      proliferation, elevated intracellular calcium concentration, decreased the
      expression of K10, and increased the expressions of INV, FIL, and TG. These data
      indicate that the endogenous activation of PKC regulates the expressions of the
      late differentiation markers, and that the exogenous activation of PKC by PMA
      results in the induction of terminal differentiation. Because the cellular
      effects of PMA were accompanied by differential down-regulations of the sensitive
      PKC isoforms in proliferating and differentiating cultures, our findings argue
      for the differential roles of the existing PKC isoforms in the regulation of
      cellular proliferation and high cell density-induced differentiation of HaCaT
      cells.

PMID- 14714563
TI  - Routine flow cytometric immuno-staining of T-cell perforin is preserved using
      diethylene glycol for erythrocyte-lysis but lost by the use of ammonium chloride.
AB  - The system of perforin-containing lytic granules of cytotoxic lymphocytes plays
      an important role in the immune defense machinery. Investigating the capacity and
      efficacy of this system in and ex vivo is helpful to understand immune responses
      and their modulation by therapeutic interventions. With regard to its
      pathophysiological function, we recently demonstrated a substantial increase of
      perforin-positive CD8+ T cells in the peripheral blood of patients with acute
      exacerbated psoriasis and severe generalized drug reactions, and, in marked
      contrast, a highly significant perforin-depletion and a perforin
      hyperreleasability in atopic dermatitis (AD). To streamline the perforin staining
      procedure, isolation of peripheral blood mononuclear cells (PBMC) by Ficoll
      density centrifugation was to be replaced by lysis of erythrocytes. Ammonium
      chloride lysis, however, reduced the perforin content of CD8+ T cells
      substantially (up to 75-100%) as compared with Ficoll isolation of PMC.
      Incubation of cells in concanamycin A, a selective inhibitor of H+-ATPases,
      resulted in a similar loss of perforin staining pointing to the critical
      influence of lysosomal pH. Using diethylene glycol-mediated erythrocyte lysis,
      perforin was well preserved to be readily detectable by immuno flow cytometry.
      Representative examples of the application of this optimized perforin staining
      procedure as well as accumulated data are given for various dermatological
      disorders (psoriasis, atopic dermatitis, cutaneous drug reactions, graft-versus
      host disease (GVHD) with strong involvement of the cytotoxic T-cell population.
      Our findings may help to explain recent conflicting reports about a widely
      varying range of the portion of perforin-positive cells in healthy individuals as
      a reflection of such artificial methodological influences.

PMID- 14714564
TI  - In vivo alteration of the keratin 17 gene in hair follicles by oligonucleotide
      directed gene targeting.
AB  - Using intradermal injection of a chimeric RNA-DNA oligonucleotide (RDO) or a
      single-stranded oligonucleotide (ssODN) into murine skin, we attempted to make a
      dominant mutation (R94p) in the conserve alpha-helical domain of keratin 17
      (K17), the same mutation found in pachyononychia congenichia type 2 (PC-2)
      patients with phenotypes ranging from twisted hair and multiple pilosebaceous
      cysts. Both K17A-RDO and -ssODN contained a single base mismatch (CGC to CCC) to
      alter the normal K17 sequence to cause an amino acid substitution (R94P). The
      complexes consisting of oligonucleotides and cationic liposomes were injected to
      C57B1/6 murine skin at 2 and 5 day after birth. Histological examination of skin
      biopsies at postnatal day 8 from several mice showed consistent twisted hair
      shafts or broken hair follicles at the sebaceous gland level and occasional
      rupture of the hair bulb or epidermal cyst-like changes. In the injected area,
      the number of full anagen hair follicles decrease by 50%. Injection of the
      control oligonucleotide, identical to K17A-RDO but containing no mismatch to the
      normal sequence, did not result in any detectable abnormality. The frequency of
      gene alteration was lower than 3%, according to the restriction fragment length
      polymorphism (RFLP) analysis of the genomic DNA isolated by dissection of hair
      follicles from slides. Although intradermal injection of K17A-RDO or K17-ssODN
      caused a dominant mutation in K17 affecting hair growth and morphology, these
      phenotypic changes were transient either due to the compensation of K17 by other
      keratins or the replacement of the mutated cells by normal surrounding cells
      during hair growth.

PMID- 14714565
TI  - Cytochrome p450A1 polymorphisms in a Caucasian population with porphyria cutanea
      tarda.
AB  - Porphyria cutanea tarda (PCT) is the most frequent porphyria in humans. The
      familial type is in contrast to the sporadic type due to an inherited defect of
      the uroporphyrinogen-II-decarboxylase (URO-D) and both types need additional
      porphyrinogens to lead to the clinical manifestation of the disease. Various
      factors such as xenobiotics (i.e. polycyclic aromatic hydrocarbons), alcohol,
      hormones and viral liver infections (hepatitis B and C) are known to induce
      porphyria. Cytochrome p450 enzymes play a crucial role in the metabolism of
      porphyrogens and therefore might have an important influence on the pathogenesis
      of hepatic porphyrias. Association of CYP1A2 polymorphisms with susceptibility to
      both types of PCT has already been described in Danish patients. We investigated
      65 caucasian patients with PCT in comparison to a healthy control group
      concerning the tpe of PCT and the cytochrome p4501A1 polymorphisms (m1, m2 and
      m4) using polymerase chain reaction (PCR) and a restriction fragment length
      polymorphism. We found an increased incidence of the m4 polymorphism in the
      familial type of PCT (odds ratio 5.5, P-value 0.01), whereas the m1 and m2
      mutations, might be provoked by a higher susceptibility to porphyrogens via the
      cytochrome p4501A1 m4 polymorphism.

PMID- 14714566
TI  - Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages.
AB  - The adult hair follicle dermal papilla (DP) and dermal sheath (DS) cells are
      developmentally active cell populations with a proven role in adult hair follicle
      cycling activity and unique inductive powers. In stem cell biology, the hair
      follicle epithelium has recently been the subject of a great deal of
      investigation, but up to now, the follicle dermis has been largely overlooked as
      a source of stem cells. Following the sporadic appearance of muscle, lipid and
      bone-type cells in discretely isolated follicle DP and DS cell primary cultures,
      we demonstrated that cultured papilla and sheath cell lines were capable of being
      directed to lipid and bone differentiation. Subsequently, for the first time, we
      produced clonal DP and DS lines that had extended proliferative capabilities. Dye
      exclusion has been reported to be an identifying feature of stem cells;
      therefore, clonal papilla and sheath lines with differing capacity to exclude
      rhodamine 123 were cultured in medium known to induce adipocyte and osteocyte
      differentiation. Both DS- and DP-derived clones showed the capacity to make lipid
      and to produce calcified material; however, different clones had varied behaviour
      and there was no obvious correlation between their stem cell capabilities and dye
      exclusion or selected gene expression markers. As a highly accessible source,
      capable of being discretely isolated, the follicle has important potentially as a
      stem cell source for tissue engineering and cell therapy purposes. It will also
      be interesting to compare follicle dermal stem cell properties with the broader
      stem cell capabilities discovered in skin dermis and investigate whether, as we
      believe, the follicle is a key dermal stem cell niche. Finally, the discovery of
      stem cells in the dermis may have implications for certain pathologies in which
      abnormal differentiation occurs in the skin.

PMID- 14714567
TI  - Evolutionary characteristics of HIV type 1 variants resistant to protease
      inhibitors in the absence of drug-selective pressure.
AB  - To understand the evolutionary characteristics of HIV-1 variants resistant to
      protease inhibitors (PI), the replicating plasma virus was analyzed in three
      patients shifted to PI-sparing regimen after virological failure. The dynamic
      features of carryover mutations associated with PI resistance in the absence of
      selective pressure on the protease gene indicate that viral variants resistant to
      reverse transcriptase inhibitors and bearing mutations of the protease sequence
      can maintain efficient replication capacity in vivo.

PMID- 14714568
TI  - Purinergic receptor expression in the regeneration epidermis in a rat model of
      normal and delayed wound healing.
AB  - This study investigated changes in the protein expression of purinergic receptors
      in the regenerating rat epidermis during normal wound healing, in denervated
      wounds, and in denervated wounds treated with nerve growth factor (NGF), where
      wound healing rates are normalized. Excisional wounds were placed within
      denervated, pedicled, oblique, groin skin flaps, and in the contralateral abdomen
      to act as a control site. Six rats had NGF-treated wounds and six had untreated
      wounds. Tissue was harvested at day four after wounding. The re-epithelializing
      wound edges were analyzed immunohistochemically for P2X(5), P2X(7), P2Y(1) and
      P2Y(2) receptors, and immunostaining of keratinocytes was quantified using
      optical densitometry. In normal rat epidermis, P2Y(1) and P2Y(2) receptors were
      found in the basal layer where keratinocytes proliferate; P2X(5) receptors were
      associated with proliferating and differentiating epidermal keratinocytes in
      basal and suprabasal layers; P2X(7) receptors were associated with terminally
      differentiated keratinocytes in the stratum corneum. In the regenerating
      epidermis of denervated wounds, P2Y(1) receptor protein expression was
      significantly increased in keratinocytes (P<0.001) but P2Y(1) receptors (P<0.001)
      compared with untreated denervated wounds. In innervated wounds, NGF treatment
      enhanced expression in keratinocytes. P2X(5) (P>0.001) and P2Y(1) receptor
      protein (P<0.001) expression in keratinocytes. P2X(7) receptors were absent in
      all experimental wound healing preparations. P2X(5), P2X(7), P2Y(1) and P2Y(2)
      receptor protein expression in the regenerating epidermis was altered both during
      wound healing and also by NGF treatment. Possible roles for purinergic signalling
      and its relation to NGF in wound healing are discussed.

PMID- 14714570
TI  - hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous
      malignant melanoma cell lines and can be induced further by ultraviolet-B
      irradiation.
AB  - Microsatellite instability and reduced expression of mismatch repair proteins
      were reported in melanomas. However, little is known about mutational changes of
      the mismatch repair genes in radial growth-phase melanoma especially following
      UVB irradiation. To investigate these changes, an in vitro system consisting of
      radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was
      established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for
      mutational changes of exon regions 13,16 and 19 (hMLH1) and 6,7 and 12 (hMLH2) of
      these genes before and after irradiation. The genomic DNAs were PCR amplified and
      the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and
      transversion (G-->, A-->T) mutations were found in exons 6,16 and 19. Some were
      present in both the sham-irradiated and UV-irradiated cells but others were only
      detected after UVB irradiation. hMLH1 and hMLH2 gene mutations occur early in
      melanoma tumorigenesis. The ability of UVB irradiation to induce additional
      mutations in these repair genes suggests its possible role in melanoma
      pathogenesis. Further investigation will be needed to determine whether mutations
      such as these contribute to the development of microsatellite instability in
      melanoma.

PMID- 14714571
TI  - De novo mutations in monilethrix.
AB  - Mutations in the hair keratins hHb1 and hHb6 have been recently reported to cause
      monilethrix, an autosomal dominant hair shaft disorder, characterized by variable
      degrees of hair fragility and follicular hyperkeratosis. We found 10 families
      with monilethrix in whicn the parents were not clinically affected, and sequenced
      the hair keratin hHb1, hHb2 and hHb6 genes in seven patients. In five patients no
      mutations were found, while in two patients we identified de novo germline
      missense mutations at the helix termination motif: E402K (hHb6) and E413K (hHb1).

PMID- 14714572
TI  - HIV type 1 diversity in northeastern Romania in 200-2001 based on phylogenic
      analysis of pol sequences from patient failing antiretroviral therapy.
AB  - Protease and the first half of reverse transcriptase from 71 Romanian patients
      failing highly active antiretroviral therapy (HAART) have been sequenced and
      phylogenetically analyzed. These analyses show that 70 patients were infected
      with subtype F1 and one with subtype C. The pattern of drug resistance mutations
      in subtype F1-infected patients failing HAART is similar to that described for
      subtype B strains. These results show that the diversity pattern of HIV type 1
      infection in Romania has remained steady over a decade, with subtype F1 remaining
      the predominant viral form. The circulation of subtype F1 in Romania has the
      potential to be a source of this HIV-1 subtype in Europe..

PMID- 14714573
TI  - [Cushing syndrome/Cushing disease].

PMID- 14714575
TI  - Gastrointestinal injuries during laparoscopy.

PMID- 14714574
TI  - [50th anniversary of the Revista Alergia Mexico].

PMID- 14714576
TI  - Monitoring health in Europe: opportunities, challenges and progress.

PMID- 14714577
TI  - The relationship between pulse wave velocity and pulse pressure in Chinese
      patients with essential hypertension.
AB  - Aortic pulse wave velocity (PWV) is a significant and independent predictor of
      cardiovascular disease in hypertensive subjects and in patients with end-stage
      renal disease, but there have been few studies on PWV in Chinese patients with
      essential hypertension. In this cross-sectional study, we investigated 3,156
      consecutive patients (mean age: 53.7 +/- 11.58 years) of the Hypertension
      Division of Ruijin Hospital in Shanghai. Together with sphygmomanometric blood
      pressure measurements, aortic PWV was measured using a validated automatic
      device. PWV in patients with pulse pressure (PP) > or = 60 mmHg was significantly
      greater than that in patients with PP < 60 mmHg (p < 0.01). PP and PWV were
      positively related to age (PP: r = 0.396, p = 0.001; PWV: r = 0.531, p = 0.001).
      After adjustment by age and heart rate, PWV was still closely related to PP (r =
      0.249, p = 0.001). At any given systolic blood pressure (SBP), PWV significantly
      decreased with the increase of diastolic blood pressure (DBP), whereas at any
      given DBP there was a significant increase of PWV with the increase of SBP. In
      conclusion, PWV was the major determinant of PP, and was highest in Chinese
      patients with isolated systolic hypertension, followed by those with systolic and
      diastolic hypertension, isolated diastolic hypertension, and normal blood
      pressure.

PMID- 14714578
TI  - Differing anti-proteinuric action of candesartan and losartan in chronic renal
      disease.
AB  - It has becoming clear that angiotensin receptor blockers (ARBs) show varying
      levels of angiotensin II type 1 (AT1) receptor blocking activity. Although the
      duration of activity and the efficacy on blood pressure of ARB are reported to
      vary, depending on the agents used, it has not been examined whether the effects
      on proteinuria and urinary nitrite/nitrate (NOx) excretion differ in hypertensive
      patients with chronic renal disease. In the present study, patients with
      hypertension (> 140 and/or 90 mmHg) and chronic renal disease (proteinuria >
      0.5g/day; serum creatinine < 265 micromol/l or creatinine clearance > 30
      ml/min/1.72 m2) were randomly assigned to perindopril- (n = 15), trandolapril- (n
      = 15), candesartan- (n = 17), and losartan-treated groups (n = 15), and were
      followed up for 96 weeks. All agents decreased blood pressure to the same level,
      and none of them had any effect on creatinine clearance. Candesartan,
      perindopril, and trandolapril reduced proteinuria markedly (from 3.0 +/- 0.6 to
      1.8 +/- 0.5 g/day, 2.7 +/- 0.5 to 1.6 +/- 0.4 g/day, and 2.7 +/- 0.5 to 1.7 +/-
      0.4 g/day, respectively) at 12 weeks, and the beneficial effect persisted
      throughout the study. The effect of losartan, however, diminished over the study
      period. Whereas perindopril, trandolapril, and candesartan markedly increased
      urinary NOx excretion (from 257 +/- 23 to 1,011 +/- 150 micromol/day, 265 +/- 70
      to 986 +/- 130 micromol/day, and 260 +/- 62 to 967 +/- 67 micromol/day at 12
      weeks, respectively), a relatively blunted increase was observed with losartan
      (from 309 +/- 42 to 596 +/- 64 micromol/day). In conclusion, renal action of ARB
      varies, with relatively less proteinuria-sparing, as well as NOx-enhancing,
      effects observed with candesartan showing the greatest reduction of proteinuria
      and greatest enhancement of NOx. Furthermore, renal nitric oxide may contribute
      to the renal protective action of these agents when administered to patients with
      chronic renal disease.

PMID- 14714579
TI  - Relationship between polymorphism of the angiotensin-converting enzyme gene and
      the response to angiotensin-converting enzyme inhibition in hypertensive
      patients.
AB  - The aim of this study was to investigate the relationship between polymorphism of
      the anglotensin-converting enzyme (ACE) gene and the blood pressure response to
      ACE inhibition in a hypertensive cohort. Imidapril (5-10 mg/day) or benazepril
      (10-20 mg/day) was administered for 6 weeks to 517 essential hypertensives. ACE
      gene polymorphism was examined by the polymerase chain reaction (PCR) method and
      the patients were classified as having the 190-bp deletion homozygous (DD)
      genotype, the 490-bp insertion homozygous (II) genotype, or the 490-bp insertion,
      190-bp deletion heterozygous (ID) genotype. The achieved change in systolic and
      diastolic blood pressure (SBP and DBP) was analyzed for association with
      genotypes at the ACE gene locus. The DD genotype was observed in 132 patients
      (25.5%), the ID genotype in 255 patients (49.3%), and the II genotype in 130
      patients (25.2%). The SBP reductions in the patients with the DD genotype, II
      genotype, and ID genotype were -14.5 +/- 12.7 mmHg, -14.3 +/- 13.1 mmHg and -14.0
      +/- 12.2 mmHg, respectively (p = 0.94). The DBP reductions in the patients with
      the DD genotype, II genotype, and ID genotype were -8.7 +/- 7.4 mmHg, -8.7 +/-
      7.7 mmHg and -8.5 +/- 6.7 mmHg, respectively (p = 0.96). There was no significant
      association between the ACE gene polymorphisms and the response to ACE
      inhibition. These results suggest that ACE genotype does not predict the blood
      pressure-lowering response to antihypertensive treatment with ACE inhibition.

PMID- 14714580
TI  - Plasma adrenomedullin is closely correlated with pulse wave velocity in middle
      aged and elderly patients.
AB  - Arterial stiffness as measured by pulse wave velocity (PWV) is a major predictor
      of cardiovascular disease. Adrenomedullin (AM), a hypotensive peptide, works as a
      compensatory factor for arterial sclerosis. The aim of this study was to
      investigate the relationship between PWV and the plasma concentration of AM in
      risk-loading patients. One hundred and twenty-six inpatients aged 30 to 75 years
      with or without varying degrees of atherosclerosis were investigated. Patients
      with heart and/or renal failure were excluded. The PWV was measured using an
      automatic waveform analyzer, and the plasma AM level was measured using a newly
      developed, hypersensitive immunoenzymometric assay system. The PWV increased with
      the increasing number of cardiovascular risk factors and organ damage in the
      patients. A positive correlation between the PWV and AM level was observed
      (r=0.375, p<0.0001, n=126). Seventy-four patients were receiving antihypertensive
      medications; medication did not affect the correlation. Multivariate regression
      analysis revealed that the PWV was significantly and independently associated
      with age, systolic blood pressure, and AM level. These results indicate that the
      plasma AM concentration could serve as a marker of advanced arterial sclerosis as
      estimated by increased PWV.

PMID- 14714581
TI  - Serum cystatin C level is a marker of end-organ damage in patients with essential
      hypertension.
AB  - High urinary albumin excretion rate (AER) has been associated with the presence
      of atherosclerotic vascular damages and is an independent risk factor for all
      causes of death and cardiovascular morbidity and mortality in essential
      hypertensive patients. Serum cystatin C (s-CC) is a recently identified
      nonglycosylated 13-kD basic protein that has been suggested to be a useful marker
      of glomerular filtration rate. In the present study, we investigated the
      relationship between s-CC level and end-organ damages in the kidney, heart, and
      vessels of patients with essential hypertension. Sixty patients with essential
      hypertension participated in the present study. Patients with renal failure were
      excluded. Serum-CC level was measured by a particle-enhanced turbidimetric assay.
      Left ventricular mass index (LVMI) and intima media thickness (IMT) in the common
      carotid arteries were evaluated by ultrasound images. Twenty-four-hour blood
      pressure was measured by a cuff-oscillometric method. Serum-CC level was
      negatively correlated with creatinine clearance (r=-0.617, p<0.0001). It was also
      correlated with mean 24-h systolic blood pressure (24h-SBP) (r=0.308, p= 0.0167),
      LVMI (r=0.528, p<0.0001), and IMT (r=0.539, p<0.0001). Both AER and s-CC level
      were independently associated with mean 24h-SBP. AER but not s-CC level was
      associated with HDL-cholesterol. The present study was the first to demonstrate
      that s-CC level is a useful and convenient parameter of renal function, and may
      also prove to be an early marker of the severity of end-organ damage in patients
      with essential hypertension.

PMID- 14714582
TI  - Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in
      spontaneously hypertensive rats.
AB  - Abnormal Ca2+ handling and enhanced aggregation response have been reported in
      platelets from spontaneously hypertensive rats (SHR) and patients with essential
      hypertension, and thought to be involved in the progression of target organ
      damage of hypertension. It is important to examine whether antihypertensive
      therapy can improve the abnormal platelet response in hypertension. We
      investigated the effect of antihypertensive treatment such as amlodipine and
      cilazapril on Ca2+ handling and aggregation response in SHR platelets. Four-week
      old male SHR were divided into three groups. Each group was treated with
      amiodipine (A: 10 mg/kg/day), cilazapril (C: 10 mg/kg/day) or vehicle (V) for 8
      weeks by gavage. At 12-week-old, platelet [Ca2+]i was measured with fura-2 in
      each group of SHR and age-matched Wistar-Kyoto rats (WKY) as normal control.
      Systolic blood pressure in amlodipine and cilazapril treated groups were similar
      with WKY and significantly lower than vehicle treated group (A: 124 +/- 9, C: 126
      +/- 9, WKY: 122 +/- 10 and V: 180 +/- 9 mmHg, respectively). The basal [Ca2+]i in
      the three groups of SHR were similar and higher than WKY (A: 47 +/- 1.7, C: 47 +/
      1.2, V: 48 +/- 3.9 and WKY: 40 +/- 4.0 nmol/l, respectively). There were no
      significant differences in thrombin (0.1 U/ml)-stimulated [Ca2+]i rise in the
      presence or absence of extracellular Ca2+ among the three groups of SHR and these
      were higher than WKY. Intracellular Ca2+ discharge capacity, assessed by the
      ionomycinstimulation was similar in the all groups. Thrombin-induced maximum
      platelet aggregation responses in the three groups of SHR were similar and higher
      than WKY. The antihypertensive treatment of Ca2+ antagonist or ACE inhibitor gave
      no change in intraplatelet Ca2+ metabolism in SHR. These results support the
      hypothesis that an abnormal Ca2+ handling in SHR platelet is genetically
      determined and not improved by hypotensive therapy.

PMID- 14714583
TI  - Effects of exercise training on glomerular structure in fructose-fed
      spontaneously hypertensive rats.
AB  - A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to
      decrease insulin sensitivity in rats. Although running exercise can attenuate
      these phenomena, its effect on target organ protection is not clear. We
      investigated whether exercise training has renal protective effects in this
      model. Nine-week-old spontaneously hypertensive rats were allocated to groups
      that received HFD or a control diet (control group) for 15 weeks. At the age of
      10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU
      group), temocapril, an angiotensin converting enzyme inhibitor (TEM group),
      exercise training (EX group; treadmill running), or temocapril plus exercise
      training (TEM+EX group). BP was higher in the FRU group than in the control
      group. Exercise training tended to decrease BP and temocapril treatment decreased
      BP significantly. Proteinuria was similar in the five groups. Plasma leptin
      concentration and epididymal fat weight were lower in the EX and TEM+EX groups
      than in the FRU group. In the soleus muscle of the FRU group, the composite ratio
      of type I fiber was decreased and that of type IIa fiber was increased compared
      with those in the control group. Both temocapril and exercise training restored
      these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group
      than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX
      groups and was positively correlated with plasma leptin concentration. The
      results suggest that exercise training ameliorates glomerular sclerosis through
      mechanisms other than a reduction in BP.

PMID- 14714584
TI  - Angiotensin II type 2 receptor inhibits prorenin processing in juxtaglomerular
      cells.
AB  - Long-term treatment with an angiotensin II type 1 receptor blocker (ARB) has been
      shown to decrease the plasma renin activity (PRA) of hypertensive patients,
      whereas PRA remains elevated during angiotensin-converting enzyme inhibitor
      (ACEI) treatment. In the present study, we used rat juxtaglomerular (JG) cells to
      elucidate the mechanism(s) involved in the differential regulation of PRA between
      ARB and ACEI treatment. Addition of 100 nmol/l angiotensinogen (Aogen) to JG
      cells (n=6 primary cultures) significantly increased the medium angiotensin (Ang)
      II levels from 14 +/- 2 to 440 +/- 9 pg/ml and suppressed the renin secretion
      rate (RSR) from 39.6 +/- 5.4% to 6.3 +/- 1.8% without affecting active renin
      content (ARC) or total renin content (TRC). In the Aogen-treated cells, the ACEI,
      delapril hydrochloride (CV3317, 10 micromol/l), significantly decreased the
      medium Ang II levels to 58 +/- 14 pg/ml and increased RSR to 39.8 +/- 4.1%
      without affecting ARC or TRC. The ARB, an active metabolite of candesartan
      cilexetil (CV11974, 10 micromol/l), however, significantly increased the medium
      Ang II levels and RSR to 486 +/- 15 pg/ml and 40.9 +/- 9.8%, respectively, and
      decreased ARC from 63.2 +/- 6.8 to 21.6 +/- 3.6 ng of Ang l x h(-1) x million
      cells(-1) without affecting TRC. The decreases in ARC of the Aogen+CV11974
      treated cells (n=6 primary cultures) were inhibited by an Ang II type 2 receptor
      blocker, PD123319 (10 micromol/l). JG cells (n=6 primary cultures) were also
      treated with an Ang II type 2 receptor agonist, CGP42212A (0.1 micromol/l).
      CGP42212A significantly increased RSR from 38.2 +/- 1.6% to 49.7 +/- 4.7% and
      decreased ARC from 60.8 +/- 3.0 to 25.3 +/- 2.8 ng of Ang l x h(-1) million
      cells(-1) without affecting TRC. Addition of CV11974 did not alter the RSR, ARC,
      or TRC of the CGP42212A-treated cells; however, PD123319 abolished the effects of
      CGP42212A. These results indicate that, distinct from ACEIs, ARBs inhibit
      prorenin processing of JG cells through Ang II type 2 receptors. Long-term
      treatment with an ARB may decrease PRA in part by diminishing the storage of
      active renin in JG cells.

PMID- 14714585
TI  - Reduced membrane-bound catechol-O-methyltransferase in the liver of spontaneously
      hypertensive rats.
AB  - We have previously reported that methylation of catecholamines by catechol-O
      methyltransferase (COMT) was attenuated in spontaneously hypertensive rats (SHR)
      with acute hypotension as compared with that of Wistar-Kyoto (WKY) rats. Here we
      examined the soluble (S-) and membrane-bound (MB-) COMT activities and COMT
      protein in the liver, kidney, and erythrocytes in both strains. Both the
      activities and the amounts of MB-COMT in the liver were lower in SHR than in WKY
      rats, but no such trend was found in the kidney or erythrocytes. Nor was such a
      trend observed in any of these three tissues for S-COMT. These results indicate
      that liver MB-COMT may be a relevant factor in blood pressure regulation in rats.

PMID- 14714586
TI  - Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated
      receptors in the rat kidney.
AB  - The localization of cytochrome P-450 4A, peroxisome proliferator-activated
      receptor (PPAR) alpha, and PPARgamma proteins, and the inducibility of P-450 4A
      expression and activity by PPAR agonists were determined in the rat kidney. The
      expressions of these proteins in isolated nephron segments were evaluated by
      immunoblot analysis, and the production of 20-hydroxyeicosatetraenoic acid (20
      HETE) was measured as P-450 4A activity. P-450 4A proteins were expressed
      predominantly in the proximal tubule (PT), with lower expression in the
      preglomerular arteriole (Art), glomerulus (Glm), and medullary thick ascending
      limb (mTAL), but their expression was not detected in the inner medullary
      collecting duct (IMCD). PPARalpha protein was expressed in the PT and mTAL, and
      PPARgamma protein was expressed in the IMCD and mTAL. Treatment with clofibrate,
      the PPARalpha agonist, increased P-450 4A protein levels and the production of 20
      HETE in microsomes prepared from the renal cortex, whereas treatment with
      pioglitazone, the PPARgamma agonist, affected neither of them. These results
      indicate that PPARalpha and PPARgamma proteins are localized in different nephron
      segments and the inducibility of P-450 4A expression and activity by the PPAR
      agonists correlates with the nephron-specific localization of the respective PPAR
      isoforms.

PMID- 14714587
TI  - Ultrasound assessment of the polycystic ovary: international consensus
      definitions.
AB  - The polycystic ovary syndrome (PCOS) is a heterogeneous condition, the
      pathophysiology of which appears to be both multifactorial and polygenic. The
      definition of the syndrome has been much debated. Key features include menstrual
      cycle disturbance, hyperandrogenism and obesity. There are many extra-ovarian
      aspects to the pathophysiology of PCOS, yet ovarian dysfunction is central. At a
      recent joint ASRM/ESHRE consensus meeting, a refined definition of the PCOS was
      agreed, encompassing a description of the morphology of the polycystic ovary
      (PCO). According to the available literature, the criteria fulfilling sufficient
      specificity and sensitivity to define the PCO should have at least one of the
      following: either 12 or more follicles measuring 2-9 mm in diameter, or increased
      ovarian volume (> 10 cm3). If there is a follicle > 10 mm in diameter, the scan
      should be repeated at a time of ovarian quiescence in order to calculate volume
      and area. The presence of a single PCO is sufficient to provide the diagnosis.
      The distribution of follicles and a description of the stroma are not required in
      the diagnosis. Increased stromal echogenicity and/or stromal volume are specific
      to PCO, but it has been shown that the measurement of ovarian volume (or area) is
      a good surrogate for quantification of the stroma in clinical practice. A woman
      having PCO in the absence of an ovulation disorder or hyperandrogenism
      ('asymptomatic PCO') should not be considered as having PCOS, until more is known
      about this situation. Three-dimensional and Doppler ultrasound studies may be
      useful research tools but are not required in the definition of PCO. This review
      outlines evidence for the current ultrasound definition of the polycystic ovary
      and technical specifications.

PMID- 14714588
TI  - The endometrium in stimulated cycles for IVF.
AB  - Ovarian stimulation for IVF is known to affect luteal phase function. The
      endometrium in IVF cycles is thus subject to an altered endocrinological
      environment and to a possible direct effect of the ovarian stimulation therapy.
      Factors influencing the endometrial receptivity in such cycles are poorly
      understood. Studies comparing the endometrium in IVF cycles with natural cycles
      as controls have shown premature secretory changes in the post-ovulatory and
      early luteal phase of IVF cycles, followed by a large proportion of
      dyssynchronous glandular and stromal differentiation in the mid-luteal phase.
      These findings suggest a profound modification of luteal endometrial development
      in stimulated cycles. This hypothesis is further supported by the demonstration
      of a modified endometrial steroid receptor regulation and a profound
      antiproliferative effect in IVF cycles. The time of maximal endometrial
      receptivity is defined as the implantation window and is characterized by the
      expression of various endometrial products, among which pinopodes, integrins and
      leukaemia inhibitory factor are best described. Premature expression of pinopodes
      and integrins are in line with the observation of precocious luteal
      transformation following ovarian stimulation, although the clinical relevance
      with respect to the establishment of a clinical pregnancy awaits further
      validation. Studies exploring the endometrium within the cycle of embryo transfer
      have shown a deleterious effect of severe peri-ovulatory maturation advancement
      exceeding 3 days, as no clinical pregnancies were obtained in this condition.
      Further unravelling of molecules involved in the implantation mechanism is needed
      for a better comprehension of the link between altered endometrial development
      and receptivity in IVF cycles.

PMID- 14714589
TI  - Clinical and molecular genetics of the human GnRH receptor.
AB  - A functional GnRH receptor (GnRH-R) in the anterior pituitary is critical for
      normal LH/FSH secretion, pubertal development and reproduction. Inactivating
      mutations of the GnRH-R have been identified in patients with idiopathic
      hypogonadotrophic hypogonadism. In this article we summarize phenotypic
      characteristics of these patients and focus on specific functional alterations of
      the human GnRH-R. In-vitro studies using recombinant receptor constructs
      demonstrate that GnRH-R missense mutations result in impaired ligand binding and
      reduced signal transduction, causing gonadotrophin deficiency. A detailed
      molecular understanding of receptor inactivation may help to design new GnRH
      agonists to therapeutically modulate GnRH-R function.

PMID- 14714590
TI  - A comparison of placental development and endocrine functions between the human
      and mouse model.
AB  - The placenta plays a key role in pregnancy, mediating exchanges between mother
      and fetus and maternal tolerance of fetopaternal antigens. In some species, it
      also produces hormones that ensure the maintenance of gestation and fetal well
      being. This unique organ also has considerable potential for use as a model for
      various aspects of biology. Indeed, the use of transgenic mouse models has
      greatly improved our understanding of the genetic control of placental
      development in this species and has opened up new fields of investigation in
      developmental biology. Analogous cell types have been identified among human and
      murine trophoblasts: proliferative trophoblastic cells, invasive trophoblastic
      cells and cells differentiating into syncytium, but human and mouse placentas
      differ in both morphogenesis and endocrine function. Herein, the similarities and
      differences between the human and mouse models are reviewed, with a view to
      encouraging caution in the extrapolation of results from one model to the other.

PMID- 14714591
TI  - How to make a good oocyte: an update on in-vitro models to study follicle
      regulation.
AB  - The ability to develop the technology to mature oocytes from immature oocytes in
      vitro is the ambition of many IVF clinics. If this can be successfully achieved
      then these techniques would be available to women with fertility problems. This
      would aid women at risk of premature ovarian failure, and possibly result in
      women no longer requiring an expensive drug regime and monitoring programme,
      which they currently have to undergo. The idea of harvesting immature oocytes for
      growth in vitro is not a new one, but progress has been slow in developing and
      optimizing techniques for use on humans and domestic species. At present, there
      are many technical reasons for the lack of progress in these species, such as
      length of culture and difficulty of follicle isolation. However, the major
      problem is our lack of knowledge of how the oocyte acquires developmental
      competence during its growth within the follicle. To date, culture systems have
      been developed that can support the growth and development of immature oocytes.
      These systems are beneficial in improving our knowledge of how
      autocrine/paracrine factors are involved in regulating and controlling oocyte
      development. However, only when we have a more in-depth understanding of what is
      required during development to make a viable oocyte, will we perhaps be able to
      develop in-vitro culture systems for clinical application. This review will focus
      on how analysis of early follicular growth and development, using in-vitro
      culture systems, has advanced our knowledge of the factors and process involved
      in the regulation of oocyte and somatic cell development.

PMID- 14714592
TI  - Chemically defined media and the culture of mammalian preimplantation embryos:
      historical perspective and current issues.
AB  - Considerable advances in media development for the culture of preimplantation
      mammalian embryos have been made since mouse embryos were first cultured and
      successfully transferred to foster mothers. The purpose of this review is to
      detail the history of the development of chemically defined media for the culture
      of preimplantation embryos. Two approaches have been used to determine the
      composition of chemically defined media: the 'back-to-nature' approach and 'let
      the embryo choose' or empirical optimization approach. Recent developments,
      including the supplementation of media with amino acids and the use of sequential
      media for the extended culture of preimplantation embryos, are critically
      assessed. Importantly, it is recognized that even the best media currently used
      are not optimal and inevitably cause imbalances and stress to the embryos.
      Consequently, preimplantation embryos must adapt to the culture environment in
      order to survive. The adaptations to stress that occur when embryos are placed in
      a chemically defined environment are reviewed. The implications of these various
      stresses on the patterns of gene expression in the early embryo and their
      potential long-term effects are also emphasized. The scientific and ethical
      issues raised by the commercialization of human embryo culture media are briefly
      addressed.

PMID- 14714593
TI  - Terminology associated with vitrification and other cryopreservation procedures
      for oocytes and embryos.
AB  - Over the past 30 years many cryopreservation procedures have been applied to
      oocytes, embryos, sperm, ovarian and testicular tissue. Over this time many,
      often specialized, terms have been developed for all aspects of these procedures.
      This can make it difficult for readers who are not familiar with the terminology
      or protocols to compare and evaluate different procedures. This paper describes
      the main cryopreservation procedures, the terminology associated with them, and
      briefly explains the underlying physical, chemical and biological processes. The
      aim is to help readers understand and interpret other papers on slow cooling,
      rapid cooling, ultrarapid cooling and vitrification.

PMID- 14714594
TI  - Opportunity model of collaboration: a model for assessment instrument
      development.
AB  - Collaboration between allied health educators and clinicians has a long history
      in terms of fieldwork education. Use of collaborative partnerships for practice
      endeavors and research also has been reported in the literature. Another possible
      area in which collaboration could be effective is the development of an
      assessment instrument. Collaboration can have negative and positive results,
      however, and individuals who plan an instrument development project are cautioned
      to pay attention to the collaborative nature of the project as well as to the
      instrument development task itself. This article describes a model for
      collaboration that evolved out of an instrument development project involving
      educators from the occupational therapy programs at Utica College and the
      University of Illinois, Chicago; clinicians in school-based practice; and
      occupational therapy students. Experiences from the project are used to
      illustrate concepts of the model.

PMID- 14714595
TI  - Physical therapy students' self-reports of development of clinical reasoning: a
      preliminary study.
AB  - Reports of student perceptions about the efficacy of educational tools used by
      academic and clinical instructors to facilitate clinical reasoning are limited.
      Physical therapist students' (PTSs') perceptions of tools for developing clinical
      reasoning and problem-solving skills were surveyed to determine the effectiveness
      of various teaching methods and to identify factors associated with clinical
      reasoning development. The purposes of this descriptive investigation were to
      determine (1) if factors, such as learning mode, life experience, and curriculum,
      influence PTS' perception of their clinical reasoning mastery; (2) the relative
      roles of academic and clinical instructors and the value of their pedagogic tools
      in assisting PTS with clinical reasoning development; and (3) how PTS rate their
      degree of mastery of clinical reasoning as they progress through training. A
      survey was mailed to 17 physical therapy schools in New York and 2 in New Jersey;
      156 PTS near graduation responded, yielding a 22% response rate. The survey
      instrument had 6 open-ended and 19 multiple-choice questions. Frequency analysis
      showed (1) PTS' opinion about how they would teach clinical reasoning varied with
      their preferred learning mode, (2) prior life experiences were associated with
      clinical reasoning for some individuals, (3) academic and clinical instructors
      contribute to development of clinical reasoning, (4) the best pedagogic tools
      involved case study presentations/ assignments using actual patients or
      videotapes, and (5) PTS gained confidence in their clinical reasoning ability
      while progressing through clinical education experiences. Results support
      inclusion of diverse pedagogic tools, such as case studies, and emphasizing a
      variety of learning modes to facilitate PTS' development of clinical reasoning.

PMID- 14714596
TI  - Attributes of curriculum athletic training programs related to the passing rate
      of first-time certification examinees.
AB  - The purpose of this study was twofold: (1) to identify attributes of athletic
      training programs that have been accredited by the Commission on Accreditation of
      Allied Health Education Programs (CAAHEP) as they relate to outcomes of their
      students on the National Athletic Training Association Board of Certification
      (NATABOC) examination and (2) to determine the most effective curriculum in
      preparing candidates for the examination. For all subjects, the following survey
      information was assessed: the seven domains (competencies), number of clinical
      rotation sites, grade point average requirement, faculty responsibilities,
      faculty terminal degrees, faculty K-12 experience, association with allied health
      schools, capstone course availability, and course examination similarities. Fifty
      four subjects, representing 60% of all of the program directors of CAAHEP
      accredited athletic training programs, responded in this study. Data were
      analyzed using a general linear model procedure and regression analyses. Even
      domains of athletic training, variety of rotation sites, clinical responsibility
      of faculty, faculty terminal degrees, and faculty K-12 school experience
      significantly affected the passing rate of first time certification examinees.
      Grade point average requirement, allied health school association, course
      examination format, and capstone course were not related significantly to the
      passing rate of first-time certification examinees. The most effective curricular
      model included the seven domains of athletic training, faculty clinical
      responsibilities, and faculty K-12 work experience as related to the passing
      rate. Emphasizing the domains of athletic training (competencies), having a
      variety of rotation sites, separating clinical and academic responsibilities for
      faculty, and having faculty with terminal degrees and less public school
      experience increase the passing rate of first-time NATABOC examinees. The most
      effective curricular model in affecting passing rate, according to this study,
      includes emphasizing the seven domains of athletic training (competencies),
      separating clinical and academic responsibilities of faculty, and not focusing on
      hiring faculty with K-12 work experience. Although this article focuses primarily
      on athletic training education, we believe that this study can be used as a model
      to evaluate educational programs in other allied health, competency-based
      educational programs.

PMID- 14714597
TI  - Impact of the changing health care environment on fieldwork education:
      perceptions of occupational therapy educators.
AB  - To investigate how clinical fieldwork educators and academic fieldwork
      coordinators view the impact of the changing health care environment on student
      fieldwork education, current practice, and future of the profession, a 48-item
      questionnaire assessing the influence of recent changes in the health care system
      on fieldwork education was sent to 125 occupational therapy fieldwork educators
      and coordinators (response rate 62.4%). Differences between fieldwork educators
      and coordinators were analyzed statistically using nonparametric methods. Alpha
      level was set at p < 0.01 for all statistical comparisons. Fieldwork educators
      and coordinators agreed productivity expectations, number of hours worked, and
      time spent in documentation have increased, while job security, time for
      continuing education, and quality of patient care under the current reimbursement
      system have decreased, but diverged on several other issues. Fieldwork educators
      believed reimbursement issues did not affect their ability to accept fieldwork
      students, whereas academic coordinators believed declining reimbursement had
      negatively affected fieldwork educators' ability to accept students. Factors
      thought to facilitate the fieldwork shortage included cost reductions, changes in
      reimbursement, and increased productivity demands on clinicians.

PMID- 14714598
TI  - A towards breaking the barriers: the professionalization of the radiologic
      sciences.
AB  - Radiologic science and technology has developed at a tremendous rate over the
      past century. However, the training of personnel (radiologic
      technologists/therapists) to operate this complex equipment and to perform the
      medical procedures is not uniform across the United States, nor is licensure
      required in all states. Evidence suggests that expanded technological
      responsibilities also have increasingly pressured technologists/therapists to
      perform on levels for which they have not been prepared. Thus, the need for
      restructured and expanded educational and training programs in the radiologic
      sciences is being increasingly recognized. This paper presents a rationale for
      the development of educational programs in the radiologic sciences, and it
      concludes that a baccalaureate degree is a requirement for entry-level practice.

PMID- 14714599
TI  - Eclectic perspectives on the psychology of aphasia.
AB  - This article explores the psychological changes that occur in patients who have
      suffered a stroke with resulting aphasia and examines the adjustments necessary
      to help the patient cope. The eclectic approach described in this paper examines
      the psychology of aphasia from three perspectives: effects of brain injury,
      psychological defenses and coping styles, and responses to loss. Depression,
      anxiety attacks, ego restriction, crying, euphoria, denial, anger, and a host of
      other psychological reactions can accompany stroke, sometimes causing health care
      personnel to feel overwhelmed by these psychological concomitants in their
      patients. This paper is intended as a guide to understanding the significant
      psychological adjustments many patients must undergo. Current information is
      provided to assist in evaluating and treating these patients.

PMID- 14714600
TI  - The effect of student clinical experiences on clinician productivity.
AB  - The purpose of this study was to examine the effects of student clinical
      education experiences on acute and inpatient rehabilitation clinical instructor
      (CI) productivity. The hypothesis was that CI/student teams would be more
      productive than CIs working without students. CIs (n = 5) and students (n = 6)
      from a master's in physical therapy program provided productivity data on their
      daily patient care. We examined three primary outcomes: (1) number of patients
      seen per day, (2) number of charges generated per day, and (3) number of
      evaluations performed per day. We examined clinician productivity for 4 weeks
      with a student and for 4 weeks without a student. The results indicated
      significant differences between CI/student teams compared with CI working without
      students for two outcomes: (1) number of patients seen per day and (2) number of
      charges generated per day. Presence of students did not affect significantly the
      number of evaluations performed. Overall the results of this study contribute to
      research showing that student physical therapists positively affect clinician
      productivity.

PMID- 14714601
TI  - Reliability and validity of an objective structured clinical examination for
      physical therapy students.
AB  - The purpose of this study was to examine the reliability and validity of an
      objective structured clinical examination (OSCE) for students in the first year
      of a 2-year physical therapy program. Forty-eight students were examined at eight
      stations in one of two duplicate OSCE circuits. The stations evaluated skills
      required for the management of persons with chronic musculoskeletal conditions.
      At each station, students were required to interact with patients, demonstrate
      techniques, or interpret observations. Checklists were used to score all
      stations, which had equal values. The associations among stations were examined
      using Pearson's correlations and Cronbach's alpha. A two-way analysis of variance
      (ANOVA) with repeated measures was used to determine differences among stations
      and between circuits. The validity of the OSCE was evaluated by determining the
      correlations between scores on the stations and performance in a subsequent
      clinical practicum. Correlations between stations were r = -0.14 to 0.33 and
      between stations and clinical performance were r = -0.28 to 0.27. Cronbach's
      alpha was 0.48. The ANOVA revealed significant differences among stations (F =
      62.6, p = 0.000) but not between circuits (F = 1.8, p = 0.185). There was no
      significant interaction between circuit and station (F = 1.1, p = 0.356). There
      was poor internal consistency of the OSCE, and it did not predict clinical
      performance. Further research is required to determine if a larger number of
      stations can reliably and validly assess clinical skills of physical therapy
      students.

PMID- 14714602
TI  - Examining attitudes of specialist physicians regarding physician assistant
      referrals.
AB  - Referral of a patient from a primary care provider to a referral specialist
      physician for consultation is an important link in the continuum of patient care.
      Although the relationship between the physician assistant (PA) and supervising
      physician has been studied extensively, the effectiveness of the relationship
      between the primary care PA and the referral specialist physician is unclear. The
      purpose of this study was to examine the attitudes of the referral specialist
      physician toward direct referral of patients from primary care PAs. A random
      sample of 5,000 specialist physicians in five specialty areas across the United
      States were surveyed to determine their willingness to accept referrals from PAs,
      their attitudes about the appropriateness of PA referrals, and reasons for
      dissatisfaction, if any. Data analysis revealed that specialist physicians
      generally are willing to accept patient referrals from primary care PAs and that
      specialist physicians generally are satisfied with the appropriateness and
      timeliness of referrals from PAs. Whether or not the specialist physician
      employed (supervised) a PA in his or her own practice made a significant
      difference in level of satisfaction with PA referral. To determine the
      significance of these results, more research is needed to determine specialist
      physician satisfaction with referrals from primary care physicians compared with
      PAs.

PMID- 14714603
TI  - Effectiveness of service learning and learning through service in dietetics
      education.
AB  - Positive assessments of service learning as a teaching methodology have
      stimulated colleges and universities to adopt service learning in their
      curricula. This study was undertaken to determine whether service learning could
      be implemented effectively as a teaching methodology in dietetics education. A
      total of 49 undergraduate students who were enrolled in Nutrition for the Aging
      course participated in a service learning project. During 5 weeks of the service
      learning project, students interacted with and assisted clients of the federal
      Elderly Nutrition Program (Title IIIc). Orientation to the project, reflection on
      the experience, and evaluation were important components of this project.
      Evaluation indicated that service learning was an effective teaching method in
      the dietetics curriculum. Students reported that they were able to integrate the
      classroom content with real-life experience and learned more while doing so.
      Service learning had a positive effect on learning by bringing additional
      personal, professional, and spiritual context to the subject content taught in
      the classroom and on an understanding of community resources and needs.

PMID- 14714605
TI  - Evolution of an interdisciplinary curriculum.

PMID- 14714604
TI  - Increasing dental hygiene student diversity: life-performance questions as
      alternative admissions criteria.
AB  - The goal of this study was to create a race/ethnic-neutral admission process. An
      increase in student diversity in the Northern Arizona University Dental Hygiene
      Program (NAU DH) was accomplished through modification of its acceptance process.
      Sixty students, 22% underrepresented minority (URM), were selected using
      alternative criteria compared with 6.7% URM that would have been accepted using
      traditional criteria. For the purpose of this study, URM are defined as African
      American, Hispanic, Native American, or bicultural, groups that are
      underrepresented in dental hygiene. Six life-performance questions were added on
      the written application and were designed to assess the candidates' personal
      characteristics, including (1) leadership, (2) community service, (3) realistic
      self-appraisal, (4) personal support system, (5) ability to deal with racism, (6)
      ability to set goals and self-responsibility. Scores from the response to these
      questions were used as part of the total selection criteria. Data analysis
      revealed that white candidates scored higher than URM candidates on grade point
      average (GPA), science GPA, and total points, yet both groups scored the same on
      life-performance questions. On the basis of these findings, we conclude that
      alternative criteria in the acceptance process more fairly assesses candidates'
      qualifications and increases the diversity of the NAU DH student population.
      These alternative acceptance criteria may serve as a model for dental hygiene and
      other allied health programs.

PMID- 14714606
TI  - Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and
      without Helicobacter pylori.
AB  - Helicobacter pylori (HP) has been proposed as a mechanism of functional
      dyspepsia, but its role is still unclear. Our aim was to investigate the
      association between HP infection and dyspeptic symptoms and to verify whether the
      infection affects the pathophysiological mechanism of functional dyspepsia. The
      presence of HP and its association with dyspeptic symptoms were studied in 326
      patients. Also, the effect of HP infection on solid/liquid gastric emptying
      rates, gastric sensitivity, and accommodation to meal was studied. HP was present
      in 17% of the patients, who showed symptom prevalence similar to that of HP
      negative patients. Presence of HP did not significantly affect gastric emptying
      rates for solids and liquids, discomfort sensitivity thresholds (8.7 +/- 0.3 vs
      9.8 +/- 0.9 mm Hg), or meal-induced gastric relaxation (133 +/- 12 vs 125 +/- 29
      ml; all P's NS). In conclusion, in patients with functional dyspepsia the
      presence of HP infection does not seem to affect significantly the overall
      prevalence of symptoms or the gastric sensory-motor functions.

PMID- 14714607
TI  - Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult
      subjects.
AB  - This study aimed to evaluate the correlation between symptoms and endoscopic
      findings in reflux esophagitis. Subjects, 8031 persons without medication for
      gastrointestinal disease, were briefly asked about the presence of heartburn,
      dysphagia, odynophagia, and acid regurgitation by associated medical staff before
      endoscopy for assessment of esophagitis utilizing the Los Angeles Classification.
      Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and
      2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had
      odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis
      indicated that the symptom most related to esophagitis was heartburn (odds ratio:
      2.46), although approximately 40% of subjects with grade C or D did not complain
      of heartburn. Regarding the other symptoms, less than 30% subjects with severe
      esophagitis complained of the symptoms and the odds ratio was approximately 1.
      These results indicate that endoscopic esophagitis was not equivalent to any
      reflux symptoms from which subjects suffered in their daily lives.

PMID- 14714608
TI  - Elevated intraesophageal pressure in patients with achalasia: a common and
      important manometric finding.
AB  - There is a subgroup of patients with achalasia in which manometry shows elevated
      intraesophageal pressure, expressed by elevation of esophageal baseline relative
      to gastric pressure. The aim of this study was to determine the prevalence of
      elevated intraesophageal pressure in patients with achalasia and its relationship
      to clinical, radiographic, endoscopic, and other manometric findings. Manometric
      studies of 62 patients with achalasia were analyzed and elevated intraesophageal
      pressure was considered any positive elevation of esophageal baseline relative to
      gastric pressure. Multiple regression analysis was used to determine independent
      risk factors associated with elevated intraesophageal pressure. Elevated
      intraesophageal pressure was found in 32 patients (51.6%). Lower esophageal
      sphincter pressure was the only independent variable associated with elevated
      intraesophageal pressure (P = 0.0167). Mean lower esophageal sphincter pressure
      was significantly higher in patients with elevated compared to those with normal
      intraesophageal pressure (34 +/- 1.96 vs 26.5 +/- 1.73 mm Hg; P = 0.006). In
      addition, lower esophageal sphincter pressure had a positive correlation with
      intraesophageal pressure (r = 0.49, P < 0.001). Conversely, no correlation was
      found between elevated intraesophageal pressure and various symptoms, disease
      duration, radiologic dilation, a finding of retained fluid during endoscopy, and
      esophageal length. We conclude that elevated intraesophageal pressure is a common
      manometric finding in patients with achalasia, with a prevalence of 51.6%, and is
      associated with significantly higher lower esophageal sphincter pressure.

PMID- 14714610
TI  - COX-2 is essential for EGF induction of cell proliferation in gastric RGM1 cells.
AB  - Growth factors upregulate cyclooxygenase-2 (COX-2) expression and extracellular
      signal-regulated kinase (ERK) activity, yet little is known regarding the
      interaction between COX-2 and ERK in terms of mitogenic signal transduction
      pathways in gastric epithelial cells. Therefore, we examined the role of COX-2 in
      EGF-induced proliferation of gastric epithelial RGM1 cells. EGF treatment
      significantly induced ERK activity (peaked at 30 min) and significantly increased
      COX-2 protein (peaked at 6 hr), production of prostaglandin E2 (PGE2), and cell
      proliferation. MEK inhibitor (PD98059) decreased ERK activity and cell
      proliferation induced by EGF. The selective COX-2 inhibitor (NS-398)
      significantly reduced EGF-induced cell proliferation. Exogenous PGE2 partly
      reversed the NS-398-induced inhibitory action on cell proliferation, clearly
      indicating the importance of PGE2 in mitogenic pathway. The induction of COX-2
      protein by EGF was completely blocked by preincubation with MEK inhibitor. These
      results suggest that the ERK-COX-2 pathway is critical for EGF-induced
      proliferation of gastric epithelial cells.

PMID- 14714609
TI  - Expression of urokinase-type plasminogen activator and its receptor in gastric
      fibroblasts and effects of nonsteroidal antiinflammatory drugs and prostaglandin.
AB  - In acute inflammatory condition, little is known about the expression of the
      urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in the gastric
      fibroblasts. To clarify the role of human gastric fibroblasts in acute
      inflammatory conditions such as gastric ulcer, the effects of interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha on the expression of uPA and uPAR,
      which were suggested to be associated with tissue remodeling, in gastric
      fibroblasts were investigated. The expression level of uPA mRNA and the amount of
      uPA antigen increased significantly on treatment with each concentration of IL
      1beta (1 and 10 ng/ml) and 10 ng/ml TNF-alpha. On the other hand, the amounts of
      uPA antigen on cell surfaces were not affected significantly by IL-1beta and TNF
      alpha stimulation. The expression level of uPAR mRNA increased in a dose
      dependent manner on IL-1beta stimulation. The effect of indomethacin on uPA and
      uPAR expression in these cells was also examined. When gastric fibroblasts were
      treated with 50 microM indomethacin, the expression level of uPA mRNA decreased
      significantly, and the amount of uPA antigen in the culture medium and on cell
      surfaces decreased significantly with indomethacin in a dose-dependent manner.
      The increased uPAR mRNA expression caused by IL-1beta was reduced to the basal
      level by treatment with 50 microM indomethacin. Furthermore, we investigated the
      role of prostaglandin E2 (PGE2), which is suggested to play major roles in acute
      inflammation of the stomatch, on uPA and uPAR expression in gastric fibroblasts.
      The expression level of uPAR mRNA and the amount of uPA antigen on cell surfaces
      increased in a dose-dependent manner on treatment with PGE2 (10 and 50 ng/ml).
      These results suggest that uPA and uPAR expression in gastric fibroblasts is
      involved in the regulating system of PGE2 and that NSAIDs may delay healing of
      gastric mucosal injury in part through suppressing uPA production via inhibition
      of endogenous PG production.

PMID- 14714612
TI  - Viscoelastic behavior of small intestine in streptozotocin-induced diabetic rats.
AB  - Diabetes is associated with remodeling of the morphology and elastic properties
      of the small intestine. This study aims to study remodeling of the viscoelastic
      (time-dependent) properties of the small intestine during experimental diabetes.
      Stress relaxation tests were performed on the duodenum, jejunum, and ileum in 10
      nondiabetic and 28 streptozotocin (STZ) -induced diabetic rats. The rats were
      made diabetic by a single intraperitoneal injection of 50 mg/kg STZ. The diabetic
      rats were allocated into groups living four days or one, two, or four weeks after
      the induction of diabetes (N = 7 in each group). The mechanical test was
      performed using a machine that rapidly stretched the intestinal tube to 40% more
      than the resting length. The intestinal diameter and wall area were obtained from
      digitized images of the intestinal segments at no-load and zero-stress states.
      The stress (force per area) was computed and a reduced-stress relaxation function
      was applied. The log decay parameter C and the slow and fast time constants tau1
      and tau2 were computed. STZ-induced diabetes was associated with a progressive
      increase in the wall thickness and wall cross-sectional area (P < 0.05). tau1 and
      tau2 increased and C decreased. The slope alpha became consistently less negative
      (P < 0.05), and the stress after 600-sec relaxation gradually increased during
      diabetes (P < 0.01). In conclusion, the viscoelastic behavior of the intestinal
      wall changed during the development of diabetes.

PMID- 14714611
TI  - Effect of motilin on endogenous release of insulin in conscious dogs in the fed
      state.
AB  - The aim was to investigate the insulin-releasing activity of motilin during and
      after feeding. A single intravenous bolus injection of motilin (0.01-0.3
      microg/kg) dose-dependently stimulated endogenous release of insulin in the
      postprandial state. The insulin-releasing activity of motilin in the fed state
      was completely abolished by pretreatment with atropine or hexamethonium and was
      partly inhibited by ondansetron. Truncal vagotomy also greatly suppressed the
      motilin-induced insulin release. While phentolamine significantly enhanced
      insulin release in response to motilin, propranolol significantly inhibited this
      response in both states. The motilin-induced insulin release in the fed states
      was not accompanied by any changes in glucose concentrations. In conclusion,
      while the physiological significance remains unclear, these results indicate that
      physiological doses of motilin stimulate endogenous release of insulin via a
      vagally cholinergic muscarinic pathway, and that adrenergic and 5
      hydroxytryptamine3 receptors are also involved in this response, in the dog.

PMID- 14714613
TI  - Incidence of advanced adenomas of the rectosigmoid colon three years and five
      years after negative flexible sigmoidoscopy in 4010 patients.
AB  - Flexible sigmoidoscopy is recommended for persons at average risk for colorectal
      cancer. A follow-up is advised in 3 to 5 years, although the outcomes are not
      well established. We designed a large, prospective study of an unselected
      population to measure the incidence of advanced adenomas at flexible
      sigmoidoscopy 3 and 5 years after an initial negative examination. Adenomas were
      considered advanced if they were villous, tubulovillous, high-grade dysplasia,
      adenocarcinoma, or > or = 10 mm in size. We evaluated 8121 patients referred for
      flexible sigmoidoscopy and 4010 met the inclusion criteria. Group 1 had flexible
      sigmoidoscopy between 3 and 4 years and Group 2 between 5 and 6 years after a
      negative examination. Group 1 included 1300 patients with an incidence rate for
      advanced adenomas of 0.9% (12/1300) and Group 2 included 2710 patients with an
      incidence rate for advanced adenomas of 1.1% (30/2710). When the two group were
      subdivided by the presence or absence of a family history of a first-degree
      relative with sporadic colorectal cancer, the incidence rates for advanced
      adenomas between the populations were not different. Our data indicate incidence
      rates of 0.9 and 1.1% for advanced adenomas at flexible sigmoidoscopy 3 and 5
      years, respectively, after a negative flexible sigmoidoscopy, with no impact from
      a family history.

PMID- 14714614
TI  - Prognostic significance and correlation with survival of bcl-2 and TGF-beta RII
      in colon cancer.
AB  - Bcl-2 and TGF-beta receptors type II (RII) in colon carcinomas were studied in a
      series of 113 patients, to determine their prognostic significance and to
      correlate their expression with other prognostic indicators. Bcl-2 expression in
      the tumor cells showed a reverse relation with tumor size (P = 0.018),
      histological grade (P = 0.04), and stage (P = 0.013). Univariate survival
      analysis using the log rank test showed that the survival of patients with bcl-2
      positive tumors was significantly better than the survival of patients with bcl-2
      negative tumors (P = 0.02). However, when entered into a multivariate analysis
      model, it was not found to be of independent prognostic significance. TGF-beta
      RII expression was correlated with stage (P = 0.03), while no statistically
      significant correlation was found between TGF-beta RII expression and
      histological grade or survival. In conclusion, these results provide additional
      evidence for the role of bcl-2 and TGF-beta RII in carcinogenesis of the colon,
      while they do not support the use of these factors as prognostic markers in
      patients with colon cancer.

PMID- 14714616
TI  - Recurrent metastatic Klatskin's carcinoid tumor to celiac lymph nodes in a
      teenager: diagnosis by endoscopic ultrasound-guided fine needle aspiration biopsy
      with immunocytochemical correlation.

PMID- 14714615
TI  - Differential expression of intracellular apoptotic signaling molecules in tumor
      and tumor-infiltrating lymphocytes during development of invasion and/or
      metastasis of gastric carcinoma.
AB  - The presence and functional status of intracellular expression of caspase 8,
      caspase 10, cFLIP, caspase 3, survivin, and NF-kappaB was investigated in
      permeabilized tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma
      (N = 20) from primary locus, metastatic gastric carcinoma (N = 22) from malignant
      ascites, and benign gastric mucosa (N = 20) for the control. The quantitative
      analysis was based on the percentage of positive cells by a flow cytometry. The
      results showed that the six intracellular molecules were constitutively expressed
      in primary and metastatic carcinomas as well as normal epithelium in nearly all
      the patients. In particular, metastatic carcinoma revealed to significantly
      overexpress these molecules. In the analysis of TIL, the expression of these six
      molecules could usually be observed in carcinoma and normal epithelium. There was
      aberrant expression of these molecules in immune TIL within metastatic carcinoma
      nests. Taken together, the results showed the significantly different expression
      of the signaling molecules in both tumor and TIL between primary and metastatic
      carcinoma nests. Increased expression of cFLIP, survivin, and NF-kappaB in
      carcinoma might play an important role in hindering an intracellular apoptotic
      process, followed by accelerating the cancer invasion and/or metastasis.

PMID- 14714617
TI  - Naturally occurring antibodies to epithelial cell adhesion molecule (EpCAM).
AB  - Epithelial cell adhesion molecule (Ep-CAM) is an epithelial tumor-associated
      antigen that is expressed by a number of normal tissues and has been used as a
      target in many immunotherapy studies. The purpose of this study was to determine
      the incidence of serum anti-EpCAM IgG (immunoglobulin G) antibodies in colon
      cancer and tumor-free patients and to assess the tumor protective value of anti
      EpCAM antibodies. One third of both the cancer (16/48) and the control (9/27)
      patients had detectable antibodies. Although the mean antibody concentration was
      higher in cancer patients (0.048 +/- 0.120 U) than in controls (0.038 +/- 0.064
      U) the difference was not statistically significant. Western blot analysis
      revealed reactivity to multiple HT29 cell proteins including a 40-kDa protein
      (presumed to be Ep-CAM). Monoclonal anti-EpCAM 323/A3 antibody did not have a
      tumor-protective effect in murine Ep-CAM expressing colocarcinoma. We conclude
      that Ep-CAM is immunogenic not only for cancer patients, but also for tumor-free
      individuals.

PMID- 14714618
TI  - K-ras mutation and loss of heterozygosity at 17p with beta-catenin accumulation
      in intramucosal carcinoma of the ileostomy in familial adenomatous polyposis: a
      case report.

PMID- 14714620
TI  - Collagenous colitis evolving into ulcerative colitis: a case report and review of
      the literature.

PMID- 14714619
TI  - Unique inhibition of bile salt-induced apoptosis by lecithins and cytoprotective
      bile salts in immortalized mouse cholangiocytes.
AB  - Bile duct epithelium is physiologically exposed to high concentrations of bile
      salts, suggesting the presence of a cytoprotective mechanism(s). The aim of this
      study was to clarify whether bile salts cause bile duct cell damage and to
      elucidate the mechanism(s) providing protection against such an action of bile
      salts. Immortalized mouse cholangiocytes were incubated with taurocholate,
      taurochenodeoxycholate, glycochenodeoxycholate (GCDC), taurodeoxycholate, and
      tauroursodeoxycholate (TUDC), followed by flow-cytometric analysis and caspase
      activity assay to evaluate the induction of apoptosis. GCDC time-dependently
      induced caspase 3 (3.4-fold)- and caspase 9 (1.4-fold)-mediated apoptosis of
      cholangiocytes, but this was inhibited by lecithins and TUDC. Further, expression
      of cholangiocyte bile salt transporters (apical sodium-dependent bile salt
      transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) was examined by RT
      PCR and western blotting, and cholangiocyte bile salt uptake was determined using
      radiolabeled bile salts. Expression of cholangiocyte Asbt and Mrp3 was increased
      by bile salts, whereas lecithins interestingly reduced bile salt uptake to
      inhibit cholangiocyte apoptosis. In conclusion, bile salts themselves cause
      cholangiocyte apoptosis when absorbed by and retained inside the cell, but this
      is inhibited by washing out cytotoxic bile salts according to Mrp3, a rescue
      exporting molecule. Biliary lecithin is seemingly another cytoprotective player
      against cytotoxic bile salts, reducing their uptake, and this is associated with
      a reduced expression of Mrp3.

PMID- 14714621
TI  - Telomerase activity in chronic inflammatory bowel disease.
AB  - Patients with ulcerative colitis have an increased risk of developing colorectal
      cancer. Telomerase appears to be associated with cellular immortality and might
      serve as a diagnostic and prognostic marker in carcinogenesis. To test this
      hypothesis we measured telomerase by a score from 0 (no activity) to 4 (very high
      activity) in specimens obtained surgically from seven patients with
      adenocarcinoma of the colon. Intraindividual comparison was made among normal
      tissue (mean score +/- SD: 0.7 +/- 1.0), tissues adjacent to the tumor (2.7 +/-
      0.8), and the tumor center (3.0 +/- 1.0). In addition, from 18 patients with
      ulcerative colitis, 10 patients with Crohn's disease, and 14 patients without
      chronic inflammatory bowel disease, biopsies were collected from normal and
      inflamed areas of the colon. Independent of the duration (0-32 years), grade, and
      location of the diseases, the telomerase activities were comparable, ranging from
      0.4 to 1.0 in ulcerative colitis and from 0.3 to 0.6 in Crohn's disease and
      averaging 0.4 in controls. Apparently low telomerase activities are present in
      the mucosa of all patients and the enzyme is not yet upregulated in the
      potentially premalignant state of active ulcerative colitis, dismissing its
      prognostic value as an early tumor marker for this disorder.

PMID- 14714622
TI  - Chronic lipid hydroperoxide stress suppresses mucosal proliferation in rat
      intestine: potentiation of ornithine decarboxylase activity by epidermal growth
      factor.
AB  - We recently demonstrated that chronic exposure of rat intestine to sublethal
      levels of peroxidized lipids suppresses ornithine decarboxylase (ODC) activity,
      consistent with attenuated intestinal proliferation. The current study was
      designed to better understand the influence of exogenous epidermal growth factor
      (EGF) on intestinal proliferation in normal intestine and intestine that was
      challenged by oxidative stress induced by dietary consumption of peroxidized
      lipids. Male Sprague-Dawley rats (250-300 g) were fed standard chow (control) or
      peroxidized lipid chow for 4 weeks. EGF was injected intraperitoneally at a dose
      of 40 microg/kg. Intestinal proliferation was evaluated by ODC activity in fed or
      fasted states and at specified times during the circadian phase. Chronic peroxide
      consumption significantly attenuated ODC activities in association with increased
      tissue peroxide content. The suppressed ODC activities were restored to control
      values by EGF in the small intestine; in the colon, EGF increased ODC activity
      threefold over control rats given EGF. This elevated colonic ODC activity was
      correlated with decreased tissue GSSG and an increased GSH/GSSG ratio. These
      results show that EGF administration reverses the suppression of intestinal ODC
      activities induced by chronic peroxidized lipid intake. In contrast, EGF
      significantly elevates proliferative activity in the peroxide-stressed colon.
      This exaggerated proliferation may contribute to a better understanding of
      colonic susceptibility to oxidant-induced malignant transformation.

PMID- 14714623
TI  - Altered autonomic control in rat intestine due to both infection with Anisakis
      simplex and incubation with the parasite's crude extract.
AB  - Anisakis simplex IgE may bring on allergic responses such as angioedema,
      vomiting, and urticaria from eating seafood, but it is not the only etiology.
      Induced cholinergic hyperreactivity or adrenergic blockade in the target tissue
      can cause these diseases nonimmunologically also. Here we studied the effects on
      normal intestinal motility of brief A. simplex infections and in vitro exposures
      to the parasite's extract (CE). Each approach was evaluated according to its
      ability to induce cholinergic hyperreactivity or adrenergic blockade in rat
      duodenum (RD), jejunum (RJ), and ileum (RI) in vitro. Additionally, bolus
      propulsion in RD, RJ, and RI was evaluated with time in vivo utilizing animals
      infected 4 h previously with A. simplex larvae (L3) vs sham animals. Tissues,
      after inoculation of 1, 5, 10, and 20 L3, exhibited time- and dose-dependent
      motility changes after carbachol (Ch) and noradrenaline (NA), justifying our
      using herein rats from the fourth hour of infection with 20 L3. We observed a
      persistent, yet differential effect of the infection on RD, RJ, and RI responses
      to Ch or NA. It caused cholinergic (muscarinic) hyperreactivity in RD only, and
      adrenergic blockade in all other parts, and consequently increased the transit
      index in RD, not in RJ or RI. In contrast, exposing RD, RJ, and RI to CE
      persistently increased both parameters, amplitude of twitches and muscular tone,
      in all, albeit that, here also, responses to Ch and NA were CE dose dependent.
      Interestingly, sensitivity to CE was in the order RI > RJ > RD, the reverse
      situation of that observed during active infection. Thus, previously viable A.
      simplex L3, after digestion, can exert bystander disturbance in autonomic control
      in the whole intestine. Our findings demonstrate that A. simplex L3, alive or
      dead, can induce cholinergic hyperactivity and adrenergic blockade in the whole
      small intestine and, as a consequence, gastrointestinal symptoms. Significantly,
      they may do so long before parasite-specific IgE is detectably induced or despite
      the occurrence of such IgE.

PMID- 14714624
TI  - Peroxynitrite inhibits epidermal growth factor receptor signaling in Caco-2
      cells.
AB  - Intestinal mucosa serves as an important barrier that may be disrupted by
      inflammation. A complex system of cellular and humoral factors, including
      epidermal growth factor (EGF), maintains the integrity of this barrier. We
      hypothesized that peroxynitrite, generated in inflamed intestinal epithelium, can
      alter the EGF receptor function by nitrating tyrosine residues and blocking
      ligand-activated tyrosine autophosphorylation. Caco-2 cells or A431 cell
      membranes were treated with peroxynitrite or its decomposed form. Cell
      proliferation was measured by [3H]thymidine uptake. Immunoblot and
      immunoprecipitation were used to assess the tyrosine phosphorylation and
      nitration. Binding of epidermal growth factor to its receptor was detected by
      affinity labeling with 125I-EGF. Peroxynitrite inhibited EGF-induced Caco-2 cell
      proliferation and binding of EGF to its receptor in a concentration-dependent
      manner. Peroxynitrite abolished EGF-stimulated receptor autophosphorylation and
      nitrated EGF receptor tyrosine residues. Peroxynitrite generated during
      inflammation may disrupt the EGF-induced signaling in intestinal epithelial
      cells.

PMID- 14714626
TI  - Behcet's disease complicated by toxic megacolon.

PMID- 14714627
TI  - Elevated factor VIII and portal vein thrombosis.

PMID- 14714625
TI  - IgA and IgG tissue transglutaminase antibody prevalence and clinical significance
      in connective tissue diseases, inflammatory bowel disease, and primary biliary
      cirrhosis.
AB  - An association between celiac disease (CD) and other autoimmune diseases such as
      connective tissue diseases (CTD), inflammatory bowel diseases (IBD), and primary
      biliary cirrhosis (PBC) has been reported in several studies. However, a high
      rate of false positives in autoantibody testing was noted, especially when tissue
      transglutaminase (tTG) from guinea pig liver was used. Thus, the real prevalence
      of CD in CTD, IBD, and PBC is unclear. In a case-control study, 400 patients with
      CTD, 170 with IBD, 48 with PBC, and 120 healthy subjects were investigated for CD
      by the analysis of IgA and IgG tTG antibodies using the more specific human
      recombinant tTG immunoenzymatic assay. Patients and controls with positive
      findings were further tested for antiendomysial antibodies by indirect
      immunofluorescence and HLA typing, and those found positive by either of these
      tests underwent duodenal biopsy to confirm a possible diagnosis of CD. Twelve
      patients were positive for IgA or IgG tTG antibodies, showing an overall
      prevalence of 1.9%. Only 1 healthy subject (0.8%) had a low level positive
      reaction for IgA anti-tTG. Among the 12 patients and the healthy subject, only 2
      (1 SLE and 1 ulcerative colitis patient) were subsequently confirmed to be
      affected with CD by positive EMA, HLA, and small bowel biopsy findings. The
      highest rate of false positives was found in PBC patients (10.4%). For these
      reasons, serological screening testing for CD is not recommended in CTD patients
      or in subjects affected with IBD or PBC, unless there is a relevant clinical
      suspicion of CD.

PMID- 14714628
TI  - FRONTLINE--who is the psychoanalyst?

PMID- 14714629
TI  - Personal disclosure revisited.
AB  - In this paper personal disclosure is defined as a conscious verbal presentation
      to the patient by the therapist of a personal vignette accompanied by the
      appropriate dynamic formulation and resolution of a given personal area of
      conflict. It is conceptualized within theoretical formulations which consider the
      therapeutic relationship a dyad, where the reality of the patient and the reality
      of the therapist influence each other, providing the matrix through which the
      resolution of the patient's past life experiences takes place in the context of
      this new interpersonal experience. It is specifically differentiated from a
      boundary violation, because the personal disclosure is brought to the patient's
      interactional awareness not for gratification of the therapist's sexual or
      narcissistic needs, but to provoke a response in the patient's conceptualization
      of a phenomenon being presented in the session and to actively influence the
      intersubjective field. Within the conceptual framework developed in this paper,
      personal disclosure reaffirms the patient's current self-discovery and provides
      for a different formative experience. Personal disclosure is not to be used by
      the therapist as a vehicle to resolve personal conflicts or as source of personal
      gratification. When used within the context developed in this paper, personal
      disclosure enhances both the patient's therapeutic process and the therapist's
      ever-evolving growth.

PMID- 14714630
TI  - Freud's psychoanalysis of Edith Banfield Jackson, 1930-1936.
AB  - This paper is a historical study of Sigmund Freud's psychoanalysis of Edith
      Banfield Jackson. It relies on primary sources, including unpublished
      correspondence, to describe her background, the analysis itself, and her
      subsequent life. This analysis, which began in 1930, had both clinical and
      training purposes. Freud's actual methods are contrasted with his published
      recommendations in terms of anonymity, neutrality, and confidentiality. During
      this analysis, Sigmund Freud took on a number of roles in Edith Jackson's life,
      including teacher, commentator, social intermediary, recipient of her translation
      services, and recipient of her philanthropic donations. These roles are described
      in detail. The implications of Freud's actual methods in this case are fully
      discussed. Since Freud did not describe the methods he used in this case, they
      cannot be replicated, and, for clinical purposes, they are lost to history.

PMID- 14714631
TI  - Cognitive sciences and psychoanalysis: a possible convergence.
AB  - This paper compares the psychoanalytic description of inner experience with that
      of the cognitive sciences, which see it in terms of information processing. The
      two observational standpoints relate to the same mental events. The author
      considers the possibility of bringing the two descriptions into line with each
      other and of their mutual translation. The "information" processed in the deep,
      unconscious, affective, internal experience of a relational context must be
      identified. This may be possible if a general theory of mental functioning that
      allows for the data of psychoanalytic observation in terms of semantics, memory,
      and communication can be formulated. The author examines the theoretical
      tradition of psychoanalysis, and draws attention to the uncertainties to which
      Freud's metapsychology gives rise. The energy/drive theory was not only
      descriptive and clinical in nature, but also had explanatory value, which put
      psychoanalysis in contact with the other mental sciences of the time. This
      explanatory value is no longer valid today, and psychoanalytic theories since
      Freud seem to have disregarded the aspect of "explanation," leaving a theoretical
      void that has isolated psychoanalysis from the other sciences of the mind. The
      author contends that object theories may be an appropriate starting point for the
      exploration of experience in terms of learning processes and of memory traces,
      and suggests a psychoanalytic cognitivism, coupled with a personal theory to
      explain the development of the mind.

PMID- 14714632
TI  - Memory, narrative and the search for identity in psychoanalytic psychotherapy: a
      second chance.
AB  - The need to create order out of chaos is a driving force, ethologicalty
      determined, and part of the human condition. Narrative, especially autobiography
      and self narrative, helps us sort out myriad fantasies, events, and images,
      weaving them into a cohesive whole that eventually promotes self-awareness. The
      narratives of Virginia Woolf, St. Augustine, and Samuel Beckett are briefly
      described. Attachment theory and current research demonstrates that secure
      attachment is a first step in the socialization process and helps put one's life
      in perspective. The therapeutic use of narrative is demonstrated by three
      clinical vignettes of patients with various psychiatric disorders who had
      successful therapeutic outcomes.

PMID- 14714633
TI  - The contributions of Kenneth Leslie Artiss, M.D.
AB  - Kenneth Leslie Artiss (1913-2001) was an Army psychiatrist who did significant
      investigative work in schizophrenia and milieu therapy and whose broad
      scholarship led to decisively important and enduring contributions to operational
      psychiatry. After retirement from military service, he developed a bold approach
      for teaching psychodynamic theory and its applications, and he led seminars for
      psychiatry residents and other physicians for over four decades. He was among the
      first to apply psychodynamic ideas to improve oncology practice. His death in
      2001 motivated a group of his military students to memorialize his life and
      contributions and to demonstrate why they merit continuing consideration.

PMID- 14714635
TI  - On faith, hope, and possibility.
AB  - The idea of faith invites us into treacherous territory, as we try to negotiate
      the lines between hope and fear, possibility and madness. Our faith can open up
      untold possibilities or, alternatively, can leave us at the mercy of forces of
      destruction. In psychoanalysis, we need to be able to make our way through this
      difficult terrain, which necessitates fine-tuning our capacities to build the
      requisite ground on which hope might become possibility. Both Bion and Lacan have
      attempted to articulate the importance of being able to move beyond whatever is
      ostensibly known in order to be able to consider and to envision new
      possibilities. I would contend further that faith, at times, creates the
      possibility of profound growth and transformation. Several vignettes are
      presented by way of exploring the potentially transformative quality of faith.

PMID- 14714634
TI  - The role of psychodynamic understanding in the treatment of the medication
      refusing schizophrenic patient: a clinical report.
AB  - This paper describes the psychoanalytically informed treatment of a schizophrenic
      patient. The author discusses elements of a comprehensive treatment and
      illustrates how psychodynamic understanding can help avert impasses in therapy.
      In this case, for example, psychodynamic understanding helped the hospital staff
      overcome a sense of frustration and impotence in dealing with a patient who
      needed to isolate herself in order to overcome feelings of panic. Rehabilitative
      work was important, not only to recover lost or lessened capacities, but also to
      modify the patient's feelings towards external and internal objects.

PMID- 14714636
TI  - Elements of dynamics. I: Emotions and audiences.
AB  - Improved agreement about the quality and quantity of affect in psychiatric
      patients may be provided by videotaping them and averaging the scoring of the
      affects in the tapes by groups of professionals. Affects are real, observable,
      and discrete phenomena that are of central importance in psychiatric research and
      training. A natural reliability of affect reading appears to cross regional and
      cultural boundaries, when the means of groups are compared. Such means may
      provide valid and reliable scoring norms for the evaluation of psychopathology
      and treatment, and for calibration of mental health professionals' ascertainment
      of patients' affects.

PMID- 14714637
TI  - Psychoanalytic peregrinations. IV: what is phenomenology?

PMID- 14714638
TI  - On the fringing-field effect in liquid-crystal beam-steering devices.
AB  - A detailed simulation of the fringing-field effect in liquid-crystal (LC)-based
      blazed-grating structures has been carried out. These studies are aimed at
      clarifying the relationship between the width of the fringing-field-broadened
      phase profile of the blazed grating and the LC cell thickness. This fringing
      field broadening of the blazed grating's phase profile is shown to affect mostly
      the 2pi phase-step zone (fly-back zone) of the blazed grating. The results of the
      simulations carried out on the blazed-grating structure indicate two main effects
      of the fringing field: (1) reduction in the attainable diffraction efficiency and
      (2) limitation of the maximum deflection angle of the device. Both effects are
      shown to be directly linked to the broadening of the fly-back zone, which is
      shown to be proportional to the LC cell thickness.

PMID- 14714639
TI  - Simulation of mechanically ruled concave diffraction gratings by use of an
      original geometric theory.
AB  - A geometric theory is developed for a spherical concave diffraction grating that
      has variable line spacing and curved grooves and can be produced with existing
      technology. The aberration coefficients of this grating are determined. A
      comparison of these coefficients with the corresponding coefficients of
      holographic gratings and with CODE V polynomial coefficients gives a clearer
      understanding of the similarity and difference between mechanically ruled and
      holographically recorded concave gratings and allows the optimization of these
      gratings with standard computer programs.

PMID- 14714640
TI  - Simple optical profiling of complex guiding structures.
AB  - Working with complex guiding structures such as holey fibers requires coupling
      light into the input face of the structure. We use a simple in vivo technique to
      determine the scale, morphology, and orientation of the input cleave of the fiber
      without resorting to separate and more complex methods like optical imaging or
      scanning electron microscopy. Further, after obtaining the transverse scan of the
      fiber tip one can precisely position the focal spot anywhere relative to the
      fiber structure.

PMID- 14714641
TI  - Optical sensor interrogation with a blazed fiber Bragg grating and a charge
      coupled device linear array.
AB  - We present what is to our knowledge the first comprehensive investigation of the
      use of blazed fiber Bragg gratings (BFBGs) to interrogate wavelength division
      multiplexed (WDM) in-fiber optical sensor arrays. We show that the light
      outcoupled from the core of these BFBGs is radiated with sufficient optical power
      that it may be detected with a low-cost charge-coupled device (CCD) array. We
      present thorough system performance analysis that shows sufficient spectral
      spatial resolution to decode sensors with a WDM separation of 75 rhom, signal-to
      noise ratio greater than 45-dB bandwidth of 70 nm, and drift of only 0.1 rhom. We
      show the system to be polarization-state insensitive, making the BFBG-CCD
      spectral analysis technique a practical, extremely low-cost, alternative to
      traditional tunable filter approaches.

PMID- 14714642
TI  - Polarimetric fiber laser sensor for hydrostatic pressure.
AB  - A polarimetric Fabry-Perot fiber laser sensor for fluid pressure up to 100 MPa is
      investigated. The fluid acts on one of two elliptical-core fiber sections in the
      laser cavity, producing a shift in the differential phase of the two orthogonal
      polarization modes and thus a variation in the beat frequencies of the
      corresponding longitudinal laser modes. The second fiber section, with a 90
      degrees offset in the core orientation, compensates for temperature-induced phase
      shifts. The dispersion in the birefringent fiber Bragg grating reflectors is
      employed to remove the near degeneracy of the polarization mode beat frequencies
      of a given order and to improve substantially the resolution of the sensor to a
      few parts in 10(6) of the free spectral range. Further investigations address the
      effect of the fluid on the integrity of the fiber, the influence of various fiber
      coatings on the sensor response, and the intrinsic stability of erbium-doped and
      undoped sensing fibers under fluid pressure.

PMID- 14714643
TI  - Measurement of a fiber-end surface profile by use of phase-shifting laser
      interferometry.
AB  - We describe a laser interferometric system in which two objectives are used to
      measure surface profile on a connectorized fiber-end surface. By the use of the
      proposed illumination design a He-Ne laser as a point light source is transformed
      to an extended light source, which is beneficial to localize interference fringe
      pattern near the test surface. To obtain an optimal contrast of the interference
      fringe pattern, the flat mirror with an adjustable reflection ratio is used to
      suit different test surfaces. A piezoelectric transducer attached on the
      reference mirror can move precisely along the optical axis of the objective and
      permits implementation of four-step phase-shifting interferometry without
      changing the relative position between the CCD sensor and the test surface.
      Therefore, an absolutely constant optical magnification can be accurately kept to
      capture the interference fringe patterns resulting from a combination of light
      reflected from both the reference flat mirror and the test surface. The
      experimental result shows that surface profile on a fiber-end with surface
      features such as a small fiber diameter of 125 microm and a low reflection ratio
      of less than 4% are measurable. Measurements on a standard calibration ball show
      that the accuracy of the proposed setup is comparable with that of existing white
      light interferometers and stylus profilometers.

PMID- 14714644
TI  - Considerations for tolerancing aspheric optical components.
AB  - Optical designs often specify both surface form and centering (tilt and lateral
      displacement) tolerances on aspheric surfaces. In contrast to spherical surfaces,
      form and centering errors are coupled for aspheric surfaces. Current standards do
      not specify how to interpret such tolerances, and in particular they do not
      define the position of an aspheric surface that has form errors. The
      straightforward definition that uses the best-fit surface position that minimizes
      rms error has subtle problems. The best-fit surface position for aspheric
      surfaces is influenced by power error and can be highly sensitive to surface form
      errors when the derivative of aspheric departure is small. We analyze the
      conditions under which form and centering tolerances may be considered compatible
      when the best-fit surface-position definition is used. We propose alternative
      definitions of surface position that do not suffer from the same problems and
      consider their consequences for optical design and metrology.

PMID- 14714645
TI  - Shaping with fluid jet polishing by footprint optimization.
AB  - We report on a way to shape surfaces with fluid jet polishing by adjusting the
      influence function (the shape of the footprint of the nozzle) instead of changing
      the dwell time of the nozzle on the surface. In that way, the surface is
      processed homogeneously, and no dip is generated in the center of the workpiece.
      As a proof of this approach, a lambda/10 flat surface has been generated in our
      laboratory.

PMID- 14714646
TI  - Technique for determining the angular orientation of molecules bound to the
      surface of an arbitrary planar optical waveguide.
AB  - A technique to determine the angular orientation of a molecular assembly bound to
      the surface of a planar optical waveguide of arbitrary structure is described.
      The approach is based on measuring the absorption dichroic ratio by using the
      waveguide evanescent fields with orthogonal polarizations (TE, TM) and the same
      mode order to probe two molecular assemblies, (i) a reference sample composed of
      an isotropic orientation distribution of dipoles and (ii) a sample of interest.
      The isotropic sample is used to characterize the waveguide structure, which then
      allows the orientation parameters of a molecular assembly under investigation to
      be determined from a measured dichroic ratio. The method developed here is
      particularly important for applications in gradient-index and multilayer planar
      waveguide platforms because in those cases the extension of previously reported
      approaches would require a full experimental characterization of the guiding
      structure, which would be problematic and may yield inaccurate results.

PMID- 14714647
TI  - Theoretical and experimental study of the surface plasmon resonance effect on a
      recordable compact disk.
AB  - The surface plasmon resonance (SPR) effect on noble-metal surfaces has been
      explored by several investigators for the development of chemical and biological
      sensors as well as for the design of optical devices for other applications. The
      effect can be observed by use of prism couplers, diffraction gratings, and
      specially configured optical fibers. In an attempt to seek a new configuration
      that minimizes costs of fabricating media that support SPR in conjunction with
      designing a new format suitable for large-scale chemical and biological sensing,
      I have investigated the feasibility of using a commercially available, gold-type,
      recordable compact disk for observation of the SPR phenomenon. Experimental and
      theoretical results of this investigation are reported.

PMID- 14714648
TI  - Analysis of multitone holographic interference filters by use of a sparse Hill
      matrix method.
AB  - A theory is presented for the application of Hill's matrix method to the
      calculation of the reflection and transmission spectra of multitone holographic
      interference filters in which the permittivity is modulated by a sum of repeating
      functions of arbitrary period. Such filters are important because they may have
      two or more independent reflection bands. Guidelines are presented for accurately
      truncating the Hill matrix, and numerical methods are described for finding the
      exponential coefficient and the coefficients of the Floquet-Bloch waves within
      the filter. The latter calculation is performed by use of a computational
      technique known as inverse iteration. The Hill matrix for such problems is
      sparse, and thus, even though the matrix can be quite large, it may be
      efficiently stored and processed by a desktop computer. It is shown that the
      results of using Hill's matrix method are in close agreement with numerical
      calculations based on thin-film decomposition, a transfer-matrix technique. An
      important result of this research is the demonstration that Hill's matrix method
      may, in principle, be used to analyze any multiperiodic problem, so long as the
      periods are known to finite precision.

PMID- 14714649
TI  - Single-material inhomogeneous optical filters based on microstructural gradients
      in plasma-deposited silicon nitride.
AB  - Transparent hydrogenated amorphous silicon nitride (SiNx:H) coatings were
      prepared by dual-mode microwave-radio-frequency plasma-enhanced chemical vapor
      deposition. By controlling the effects of plasma density and ion energy on the
      film growth, it was possible to modify the microstructure of the coatings and
      hence the refractive index n. Using this method, we were able to vary n from 1.6
      to 2.0, at 550 nm, by adjusting the power levels of the radio-frequency and
      microwave components while keeping the gas composition (SiH4, N2) and pressure
      constant. An inhomogeneous bandpass filter with a controlled refractive-index
      depth profile was fabricated, and its optical performance was compared with that
      of its multilayer counterpart. Besides the attractive optical features of such
      single-material rugate filters, we found that the mechanical resistance of
      inhomogeneous films is superior to that of multilayer systems.

PMID- 14714650
TI  - Propagation of diffuse light in a turbid medium with multiple spherical
      inhomogeneities.
AB  - We develop a fast and accurate solver for the forward problem of diffusion
      tomography in the case of several spherical inhomogeneities. The approach allows
      one to take into account multiple scattering of diffuse waves between different
      inhomogeneities. Theoretical results are illustrated with numerical examples;
      excellent numerical convergence and efficiency are demonstrated. The method is
      generalized for the case of additional planar diffuse-nondiffuse interfaces and
      is therefore applicable to the half-space and slab imaging geometries.

PMID- 14714652
TI  - Experimental study of holographic generation of fractional Bessel beams.
AB  - We demonstrate the experimental generation of a fractional Bessel beam by
      holographic means. Such fractional modes of Bessel beams possess an intrinsic
      opening gap across concentric intensity rings on propagation. We also show that
      the opening gaps within the fractional modes are diffraction free for a working
      distance while a fractional helical wave front is maintained.

PMID- 14714651
TI  - Miniature endoscope for simultaneous optical coherence tomography and laser
      induced fluorescence measurement.
AB  - We have designed a multimodality system that combines optical coherence
      tomography (OCT) and laser-induced fluorescence (LIF) in a 2.0-mm-diameter
      endoscopic package. OCT provides approximately 18-microm resolution cross
      sectional structural information over a 6-mm field. LIF spectra are collected
      sequentially at submillimeter resolution across the same field and provide
      histochemical information about the tissue. We present the use of a rod prism to
      reduce the asymmetry in the OCT beam caused by a cylindrical window. The
      endoscope has been applied to investigate mouse colon cancer in vivo.

PMID- 14714653
TI  - Attenuation mechanism effect on filter shape in channelized dynamic spectral
      equalizers.
AB  - Free-space-based channelized dynamic spectral equalizers are theoretically
      investigated by solving the temporal-frequency-dependent power-coupling integral
      for commonly used active device technologies: liquid-crystal modulators, tilting
      micromirror arrays, and deformable gratings. Channel-filter characteristics, such
      as bandwidth and interchannel transition, are found to depend on the different
      attenuation mechanisms provided by the active devices. Such information is
      required for choosing the proper device parameters in designing channel
      equalizers and similar free-space spatially dispersed subsystems.

PMID- 14714654
TI  - High-definition imaging system based on spatial light modulators with light
      scattering mode.
AB  - We have developed a prototype high-definition imaging system using polymer
      dispersed liquid-crystal (PDLC) light valves, which can modulate unpolarized
      light with high spatial resolution and exhibit a high optical efficiency, based
      on the light-scattering effect. We fabricated high-definition light valves with a
      fine polymer-matrix structure in a PDLC film by controlling the curing conditions
      used during the photopolymerization-induced phase separation and formation
      process. This device has excellent characteristics, such as a high resolution,
      with 50 lp/mm for a limiting resolution and greater than 20 lp/mm at the 50%
      modulation transfer function point, and a reflectivity of greater than 60%. An
      optically addressable full-color projection display was designed, consisting of
      three PDLC light valves, a schlieren optical system based on shift
      decentralization optics with a xenon lamp illumination and input-image sources
      with 1.5 million pixels, including electrical image compensation of the gamma
      characteristics. We succeeded in displaying pictures on a 110-inch screen with a
      resolution of 810 TV lines and a luminous flux of 1900-2100 American National
      Standards Institute lumens.

PMID- 14714655
TI  - High-resolution photometric optical monitoring for thin-film deposition.
AB  - Real-time monitoring of thin-film deposition with high resolution is important
      for precise fabrication of thin-film devices in a technological environment with
      ever-increasing demands for smaller size and better performance. Using
      photometry, we were able to achieve a real-time optical monitoring resolution of
      film thickness that is comparable with a single atomic layer scale (i.e.,
      subnanometer). Filtering noise efficiently and compensating for sources of error
      by use of an appropriate model produced this high resolution. The procedure
      proved reliable and can be useful in the thin-film-deposition industry.

PMID- 14714656
TI  - Cross-phase modulation in polarization shift-keying lightwave systems.
AB  - We investigate the effect of cross-phase modulation in wavelength-division
      multiplexed polarization-modulation lightwave systems. Analytical expression for
      the Q factor penalty in terms of signal power, the number of channels, and other
      parameters are derived. The theory is compared with numerical experiments.

PMID- 14714657
TI  - Spectral characteristics of a regenerative semiconductor optical amplifier
      mutually injection locked with a Fabry-Perot laser diode.
AB  - The anomalous injection locking of a traveling-wave semiconductor optical
      amplifier (SOA) and a fiber-pigtailed Fabry-Perot laser diode (FPLD) linked with
      single-mode and improved side-mode suppression ratio output is demonstrated. We
      achieve this injection locking by driving the FPLD slightly below threshold and
      by feedback injecting the FPLD with fractional output of a closed-loop SOA. The
      SOA-FPLD link lases in a single FPLD longitudinal mode with a reduced linewidth
      of 0.013 nm and a maximum side-mode-suppressing ratio of 39.7 dB. A precise 3-dB
      linewidth of 45-50 MHz is also observed from the self-homodyne mode-beating
      spectrum. The optimized feedback-injecting power for the FPLD is approximately 2%
      of the SOA-FPLD linked output power of >400 microW. The variations in output
      power and in peak wavelength are not more than 0.54% and 0.06%, respectively. The
      injection-locked SOA-FPLD link is insensitive to the temperature fluctuation
      within +/- 0.25 degrees C.

PMID- 14714658
TI  - Photoelastic effect from die bonding of diode lasers.
AB  - The effect of strain induced from die bonding on the optical guiding of a ridge
      waveguide laser is examined. Measurements of the strain in a p-down-mounted InP
      based diode laser with fits to polarization-resolved photoluminescence are used
      to compute the resulting photoelastic effect in a ridge waveguide. The strain is
      found to alter the refractive indices in the material sufficiently in the
      waveguide to change the mode and reduce the optical confinement. In the far field
      the beam is calculated to be made narrow and asymmetric by the die-bonding
      strain.

PMID- 14714659
TI  - Smart optical sensors for chemical substances based on porous silicon technology.
AB  - A simple geometry optical sensor based on porous silicon technology is
      theoretically and experimentally studied. We expose some porous silicon optical
      microcavities with different porous structures to several substances of
      environmental interest: Very large red shifts in the single transmission peak in
      the reflectivity spectrum due to changes in the average refractive index are
      observed. The phenomenon can be ascribed to capillary condensation of vapor
      phases in the silicon pores. We numerically compute the peak shifts as a function
      of the liquid volume fraction condensed into the stack by using the Bruggeman
      theory. The results presented are promising for vapor and liquid detection and
      identification.

PMID- 14714660
TI  - Wind-velocity lidar measurements by use of a Mach-Zehnder interferometer,
      comparison with a Fabry-Perot interferometer.
AB  - We present the first wind-velocity profiles obtained with a direct-detection
      Doppler lidar that uses a Mach-Zehnder interferometer (MZI) as spectral
      discriminator. The measurements were performed in the lower stratosphere, between
      10 and 40 km in altitude, at the Observatoire de Haute Provence (OHP), France,
      during nighttime. They are in excellent agreement with those obtained
      simultaneously and independently with the already validated double Fabry-Perot
      interferometer (FPI) of the OHP Doppler lidar (mean difference lower than the
      combined standard deviation). A statistical analysis shows that the random error
      obtained with this experimental MZI is 1.94 times the Cramer-Rao lower bound and
      is approximately half of that given by the FPI (both operating in photometric
      mode). Nevertheless, the present MZI measurements are sensitive to the presence
      of atmospheric particles and need an additional correction, whereas the OHP FPI
      is designed to be insensitive to particulate scattering.

PMID- 14714661
TI  - Solar spectral irradiometer for validation of remotely sensed hyperspectral data.
AB  - A new solar spectral irradiometer that operates in the visible and near-infrared
      spectral ranges has been developed. This instrument takes advantage of a new
      concept optical head that collects the light that impinges on a hemispheric
      surface, thus improving the instrument angular response with respect to
      traditional devices. The technical characteristics of the instrument are
      investigated and detailed, and its radiometric calibration, performed by means of
      a Langley-like method, is discussed. A new simplified theoretical model that
      accounts for the diffuse irradiance observed in an optically thin plane-parallel
      atmosphere has been developed to improve the fit of the irradiance diurnal
      evolution. An alternative polynomial parametric representation of monochromatic
      diffuse irradiance evolution has been attempted, but satisfactory results were
      not obtained from the fitting of experimental data. The new instrument could be
      useful to carry out remote-sensing validation campaigns.

PMID- 14714662
TI  - Cloning of cytochrome P450, CYP6P5, and CYP6AA2 from Anopheles minimus resistant
      to deltamethrin.
AB  - Two new genes in the cytochrome P450 (CYP6) family 6 with complete coding
      sequences were cloned and sequenced from deltamethrin-resistant Anopheles
      minimus, a major malaria vector in Thailand. CYP6P5 encodes a protein of 508
      amino acids, while CYP6AA2 contains 505 residues. Each encoded protein contains a
      hydrophobic N-terminal region and a highly conserved heme-binding region typical
      of P450s. Alignments of deduced amino acid sequences with other insect P450 genes
      indicate a high degree of identity to insect CYP6 genes. Comparative mRNA
      expression studies using semi-quantitative RT-PCR analysis indicated that the
      relative amount of CYP6AA2 transcript was greater in the deltamethrin-resistant
      An. minimus compared to the susceptible strain. The expression of CYP6AA2 in
      deltamethrin-resistant mosquitoes is associated with development of deltamethrin
      resistance in An. minimus mosquito. The CYP6P5 transcript is equally expressed in
      both resistant and susceptible mosquitoes.

PMID- 14714663
TI  - Host-seeking activity of ixodid ticks in relation to weather variables.
AB  - Ixodid ticks were monitored in a temperate deciduous broad-leaved forest in South
      Moravia (Czech Republic). Relative abundance of the ticks collected before noon
      (10.00-12.00 h) was compared to several weather variables (air and soil
      temperatures, relative humidity, precipitation, wind speed, and derived values)
      using the Pearson correlation coefficient. The tick numbers were found to be most
      closely related to the amplitude of the soil (-5 cm) temperature between 07 h and
      14 h (TSamp, in Ixodes ricinus), and the soil temperature (TS) at noon (in
      Haemaphysalis concinna) or in the morning (Dermacentor reticulatus). While a
      growing amplitude in TSamp caused an increased host-seeking activity of I.
      ricinus and H. concinna, it suppressed the activity of D. reticulatus, a tick
      species mainly occurring in colder seasons of the year in Central Europe. The air
      temperature (TA) and relative humidity (RH) were also closely related to the tick
      activity, whereas rainfall and wind speed remained largely uncorrelated with the
      activity of the three tick species. Multiple linear regression on several
      variables (TSamp, TA, TS, TA-TS, RH) explained 48% of the variance in I. ricinus,
      47% in H. concinna, and 38% in D. reticulatus. Predictive two-variable regression
      models of relative abundance in host-seeking ticks were based on morning
      temperature (TA or TS) and morning RH as the most important environmental
      factors: they explained 32% (I. ricinus), 39% (H. concinna), and 35% (D.
      reticulatus) of the variance.

PMID- 14714664
TI  - Comparative susceptibility to oral infection with dengue viruses among local
      strains of Aedes aegypti (Diptera: Culicidae) collected at different seasons of
      the year.
AB  - The vector competence of Aedes aegypti (L.) mosquitoes, collected during the hot,
      rainy and cool seasons from different localities in Thailand, was tested for a
      correlation with a seasonal cyclic pattern of dengue incidence. Under laboratory
      conditions, some groups of mosquitoes exhibited differences in susceptibility to
      oral infection but showed no correlation to dengue cases that peak during the
      rainy season. Thus, the environmental conditions of each season, although they
      might affect a temporal change of mosquito vector competence, they might not have
      any direct effects on virus transmission patterns. Mosquito populations from
      different parts of Thailand were also likely to be homogeneous in their
      susceptibility to dengue virus during the study period. Other factors, such as
      characteristics of the virus, vector density and frequency of host-vector
      contact, should be considered for seasonal pattern of dengue diseases.

PMID- 14714665
TI  - The western black-legged tick, Ixodes pacificus, in the Sutter Buttes.
AB  - The western black-legged tick, Ixodes pacificus, was collected from Huff Canyon
      in the Sutter Buttes in north central California, Sutter County. The Sutter
      Buttes are within the Sacramento Valley and outside the normal distribution of I.
      pacificus in California. Adult I. pacificus were collected via flagging as they
      quested along deer trails; subadult life stages were collected from three species
      of lizard, Elgaria multicarinata, Sceloporus occidentalis, and S. graciosus.
      Adult ticks were tested for the presence of spirochetes using the standard IFA
      with a monoclonal antibody specific for OSPA. Of the ticks tested, 3.3% were
      identified as positive for the presence of the spirochete Borrelia burgdorferi.
      These results present the first published account of Ixodes pacificus as well as
      the first detection of B. burgdorferi in the Sutter Buttes, Sutter County,
      California.

PMID- 14714666
TI  - Anopheles dirus and its role in malaria transmission in Myanmar.
AB  - Anopheles dirus is one of the primary vectors of highly drug-resistant Plasmodium
      falciparum, which causes cerebral malaria resulting in high mortality. Mosquito
      collections were conducted in a forest wood-extraction area (Bago Division), an
      irrigated plain area near foothills (Mandalay Division), a coastal plain (from
      domestic wells in the Mudon area, Mon State) near the foothill area, as well as a
      hilly area (deep forest timber extraction camp, Tanintharyi Division) from May
      1998 to March 2000. This study examined adult bionomics of An. dirus and its
      relationship to malaria transmission as an aid in the control of malaria in
      different ecological settings in these particular regions. Within these areas,
      Mudon, Mon State, has a high incidence of malaria. To investigate this malaria,
      blood smear examinations were conducted among the local people in Mudon, Mon
      State. During the study period, malaria blood smear slide-positive rates ranged
      between 9.9% and 34.28% throughout the year. The ultimate goal of these studies
      was to help in formulating an improved malaria control program involving
      microbial control agents in this area.

PMID- 14714667
TI  - Survey of ticks collected in Mississippi for Rickettsia, Ehrlichia, and Borrelia
      species.
AB  - From November 1999 through October 2000, we tested ticks collected from
      vegetation as well as from deer, dogs, and humans for spotted fever group (SFG)
      rickettsiae, Ehrlichia chaffeensis, and Borrelia spp. spirochetes. A total of 149
      adult ticks representing four species was collected from 11 collection sites from
      southwestern to northern Mississippi. Amblyomma americanum was most commonly
      collected (n=68), followed by Ixodes scapularis (n=53). The bird tick, Ixodes
      brunneus (usually rare), was the third most commonly collected tick (n=17).
      Eleven Dermacentor variabilis were also collected. Ticks were cut longitudinally
      to make smears on three microscope slides. The remaining body parts were frozen
      at -65 degrees C for additional testing. Tick smears were stained by direct
      immunofluorescence assays (DFA) for Rickettsia spp. and Borrelia spp., while
      indirect immunofluorescence assays (IFA) were used for Ehrlichia spp. The
      corresponding tick for each positive smear was evaluated using PCR analysis. None
      of the 149 ticks tested was DFA positive for Borrelia spp. However, smears of 30
      (20%) and 32 (22%) ticks reacted with anti-E. chaffeensis sera and anti-R.
      rickettsii conjugate (known to react with several members of the spotted fever
      group), respectively. None of the ticks staining with the IFA for Ehrlichia was
      positive for E. chaffeensis using PCR. However, 23 (72%) of 32 FA-positive ticks
      for SFG rickettsiae yielded amplicons of the appropriate size when tested using a
      PCR assay for SFG rickettsiae, corresponding to an overall infection rate with
      SFG rickettsiae among the collected ticks of 15%. Smears of 12 (71%) of 17 I.
      brunneus revealed abundant bacilliform bacteria. PCR amplification of DNA from a
      single I. brunneus containing these bacteria was performed using universal
      primers for the 16S rRNA gene as well as Borrelia-specific primers. The
      predominant sequence obtained using the universal primers did not match any
      sequence in GenBank, but it showed 91% identity with an endosymbiont of
      Acanthoamoeba. Other sequences represented in the top 50 Basic Local Alignment
      Search (BLAST) scores were primarily from soil bacteria, although some similarity
      to several Anaplasma species and Ehrlichia risticii was indicated. The
      significance of this finding remains undetermined.

PMID- 14714668
TI  - A review of monomolecular surface films as larvicides and pupicides of
      mosquitoes.
AB  - Commercially available monomolecular surface films (Arosurf MSF and Agnique MMF,
      non-ionic products) are utilized as larvicides and pupicides of mosquitoes. They
      are biodegradable and spread spontaneously over the surface of the water to form
      an ultra-thin film (monomolecular layer), about one molecule in thickness. Their
      mode of action against mosquito larvae and pupae is physical rather than
      chemical. They lower the water surface tension, preventing suspension of the
      larvae and pupae at the water surface, subsequently suffocating them. They also
      interfere with emergence of the adults. Monomolecular surface film products have
      been shown to be relatively safe to non-target invertebrates and vertebrates,
      including humans. The laboratory and field efficacy of monomolecular films
      against aquatic organisms, primarily mosquitoes, is reviewed and non-target
      effects reported.

PMID- 14714669
TI  - Comparison of life table attributes from newly established colonies of Anopheles
      albimanus and Anopheles vestitipennis in northern Belize.
AB  - A life table study was conducted for recently established colonies of Anopheles
      albimanus and Anopheles vestitipennis in Belize, Central America. The colonies
      were reared in the northern Orange Walk District under uncontrolled environmental
      conditions (29-32 degrees C, 87-90% RH, and 13:11 L:D photoperiod). The mean time
      of larval development for An. albimanus was 10.8 days for males and 11.7 days for
      females. Mean times for An. vestitipennis larval development were 11.3 days for
      males and 13.5 days for females. Anopheles albimanus exhibited a 92% survival
      rate from egg hatch to adult emergence, while that of An. vestitipennis was 82%.
      Neither species showed a sex ratio that was significantly different from 1:1.
      Adult male An. albimanus lived for an average of 13.6 days, while the females
      lived for an average of 21.2 days. The An. vestitipennis adult males lived for a
      mean of 14.8 days, while the females lived considerably longer with a mean of
      25.6 days. The reproductive rate and age of mean cohort reproduction were
      calculated as 287 and 11.3 days for An. albimanus and 302 and 13.4 days for An.
      vestitipennis. The r/B and B/D ratios of 0.13 and 1.15, respectively, for An.
      albimanus and 0.1 and 1.1, respectively, for An. vestitipennis indicate that
      these species have a low potential for colonization.

PMID- 14714670
TI  - Seasonal prevalence and container preferences of Aedes albopictus in Santo
      Domingo City, Dominican Republic.
AB  - The seasonal prevalence and container preferences of Aedes albopictus (Skuse)
      were studied in the park, Parque Mirador del Norte in Santo Domingo City,
      Dominican Republic, from January to December 1994. Tire ovitraps were set along a
      transect through the park and monitored weekly while two larval surveys were
      conducted in both the park and surrounding houses using standard entomological
      methodology. No seasonal pattern of oviposition was observed with similar numbers
      of positive tire traps collected in the wet and dry season. Most of the positive
      ovitraps were located in the middle of the park. Within ovitraps, Aedes aegypti
      (L.), Ae. albopictus, Culex corniger (Theobald), Ochlerotatus albonotatus
      (Coquillett), and Toxorhynchites sp. were collected. The larval surveys found 7
      associated mosquito species, including Ae. aegypti, Ae. albopictus, Ochleotatus
      mediovittatus (Coquillett), Anopheles albimanus (Weidemann), Culex nigripalpus
      (Theobald), and Culex quinquefasciatus Say. The Ae. albopictus breeding sites
      were plastic buckets (4), rock holes (3), and Styrofoam lunch containers (3). We
      suggest that further studies should be conducted to determine its geographic
      distribution and vector potential in the Dominican Republic.

PMID- 14714671
TI  - Larval behavior of four Culex (Diptera: Culicidae) associated with treatment
      wetlands in the southwestern United States.
AB  - The diving behavior, aggregation, horizontal distribution under two food regimes,
      and response to change in ambient light level were studied for fourth instars of
      four Culex species in the laboratory. Under low food conditions, Cx.
      erythrothorax larvae dived less frequently, exhibited greater aggregation, and
      had stronger preferences for the corners of the observation chamber than did
      larvae of three congeners (Cx. tarsalis, Cx. quinquefasciatus, and Cx.
      stigmatosoma). Under high food conditions, larvae of all species were more
      sedentary than under low food conditions; however, the behavior of Cx.
      erythrothorax larvae changed comparatively little with changes in food abundance.
      Culex erythrothorax was the most responsive to disturbance (an 11% change in
      ambient light level), whereas Cx. tarsalis larvae did not respond to small
      changes in ambient light level. The behavior of Cx. erythrothorax larvae differed
      significantly from the three congeners studied. Species-specific behavioral
      differences of larvae may have contributed to the discrepancies of species
      relative abundance in larval surveys versus emerging adult mosquito collections
      at constructed wetlands noted in previous studies.

PMID- 14714672
TI  - Efficacy of microencapsulated insecticides against the sandfly, Phlebotomus
      papatasi Scopoli.
AB  - The baseline and residual activity of micro-encapsulated insecticides was
      assessed on a sandfly colony originating in the Jordan Valley, Israel. Lethal
      doses were calculated for formulations of the pyrethroids permethrin and
      cypermethrin and the organophosphates diazinon and chlorpyrifos. Cypermethrin was
      found to be more toxic than permethrin and chlorpyrifos was more toxic than
      diazinon. Accordingly, the residual activity of chlorpyrifos and cypermethrin was
      tested after 1 and 4 wk exposure of impregnated filter papers under three
      environmental conditions: Jerusalem-indoors, Jerusalem-outdoors and semi-arid
      conditions. The results showed that environmental and climatic conditions play a
      major role in the persistence of toxicity of micro-encapsulated insecticides. A
      significant loss of toxicity for both compounds was noted after 4 wk of exposure
      under semi-arid conditions.

PMID- 14714673
TI  - Repellency of aromatic turmeric Curcuma aromatica under laboratory and field
      conditions.
AB  - Three Curcuma species, Curcuma aeruginosa (pink and blue ginger), Cu. aromatica
      (aromatic turmeric), and Cu. xanthorrhiza (giant curcuma), were selected for
      investigation of mosquito repellent activity. In a laboratory study, a 95%
      ethanol extract of each plant was tested for repellent activity of Aedes togoi on
      human volunteers. Only Cu. aromatica extract showed repellency against Ae. togoi
      with ED50 and ED95 values of 0.061 and 1.55 mg/cm2, respectively. It also
      provided biting protection for 3.5 h when applied at a concentration of 25 g%.
      The ethanolic extract of Cu. aromatica was therefore chosen for further repellent
      activity under field conditions, where it had a protective effect against
      Armigeres subalbatus, Culex quinquefasciatus, and Cx. tritaeniorhynchus. The
      ethanol-extracted Cu. aromatica did not cause dermal irritation when applied to
      human skin. No adverse effects on human volunteers were observed 2 mo after
      application. Therefore, Cu. aromatica extract can be applied as an effective
      personal protection measure against mosquito bites.

PMID- 14714674
TI  - Laboratory and field evaluation of novaluron, a new acylurea insect growth
      regulator, against Aedes aegypti (Diptera: Culicidae).
AB  - Novaluron, a new chitin synthesis inhibitor type of insect growth regulator, was
      evaluated in the laboratory and field against larvae of the mosquito Aedes
      aegypti (L.). In the laboratory, the technical material showed a high level of
      activity against 2nd and 4th instar larvae. The inhibition of emergence (IE) was
      100% at concentrations of 0.25 to 1.0 microg/L. Second instars were slightly more
      susceptible than fourth instars. At the high concentration (1 ppb), most of the
      mortality occurred in the larvae, but at sublethal concentrations (for larvae)
      mortality also occurred in pupae and adults (incomplete eclosion). An EC10
      (emulsifiable concentrate containing 10% active ingredient) formulation of
      novaluron was evaluated against Ae. aegypti in water-storage containers in the
      field in Thailand. Two tests at high (0.05 to 1 mg/L) and low (1 to 20 microg/L)
      concentrations were carried out in clay jars (200 L) and plastic pails (75 L). At
      high concentrations in clayjars, we obtained 86-96% inhibition of emergence (IE)
      for about 190 d, but the mortality declined at low concentrations after 190 d. At
      much lower concentrations, in jars and plastic pails in the second experiment,
      the IE was 80-100% for 2 mo. The highest concentrations of this series (10
      microg/L in jars and 20 microg/L in pails) were active for 75 and 68 d
      respectively, losing efficacy by 82 d post-treatment. In the experiment using low
      concentrations, all treatments in jars and plastic pails failed to provide
      adequate control 90 d after treatment. These studies show that novaluron, even as
      EC10, has exceptional long-term activity against Ae. aegypti in water-storage
      containers, with higher concentrations yielding greater long-term control than
      low concentrations.

PMID- 14714675
TI  - Species composition and seasonal dynamics of mosquito larvae in the Wroclaw,
      Poland area.
AB  - A total of 13,214 larvae specimens representing eight species (Culex pipiens,
      Culiseta annulata, Ochlerotatus cantans, Ochlerotatus communis, Ochlerotatus
      excrucians, Ochlerotatus sticticus, Aedes vexans, and Anopheles maculipennis)
      from twelve sampling places in the Wroclaw area in Poland were collected between
      May and October, 1998-2000. The development rate of each mosquito species
      depended on hydrological types and various plant communities in water bodies. The
      water quality (temperature, pH and ion concentration) influenced mosquito larvae
      dynamics as well. The most abundant and constant species was Cx. pipiens. Its
      monthly population was significantly higher in the water bodies located in the
      city center as compared to those in the suburbs.

PMID- 14714676
TI  - Container surface area and water depth influence the population dynamics of the
      mosquito Culex pervigilans (Diptera: Culicidae) and its associated predators in
      New Zealand.
AB  - The density of larval mosquitoes in containers is related to adult mosquito
      ovipositional preferences and to other factors such as the abundance of
      predators. We examined the effects of anthropogenic container size and water
      depth on the population dynamics of mosquitoes and their macroinvertebrate
      predators in Wellington, New Zealand. Culex pervigilans was the only mosquito
      species observed in these containers. With the exception of one sampling date,
      throughout the year Cx. pevigilans larvae, egg rafts, and pupal exuviae were
      observed. The highest densities of Cx. pervigilans were observed in the
      containers with the smallest surface area. A multiple regression analysis was
      used to analyze the effects of container surface area and depth on the mean
      density of mosquito larvae in each container. This analysis showed larval
      densities significantly decreased with increasing container surface area, for two
      thirds of the year. Although fewer Cx. pervigilans were generally observed in
      similarly sized containers with greater depths, this effect was not statistically
      significant. The significant effect of container surface area appeared to be
      related to adult ovipositional preferences, as few observations of predators were
      made in any of the container treatments. Of the predators that were observed,
      damselfly larvae and diving beetles tended to be more common in the larger
      containers. Our results suggest that mosquitoes may have strong preferences based
      on container size alone that influence larval population dynamics, irrespective
      of the abundance of aquatic predators.

PMID- 14714677
TI  - Selected literature references to vector ecology--April-September 2003.

PMID- 14714678
TI  - Food consumption patterns of rural older African American, Native American, and
      white adults in North Carolina.
AB  - This paper describes the major food sources of selected nutrients for an
      ethnically diverse sample of older adults in rural North Carolina. A
      representative sample of 130 elders (> 70 years) completed semi-quantitative food
      frequency questionnaires. Percentages of foods most frequently consumed as the
      lead source of seven nutrients were calculated overall, by gender and ethnic
      group. Foods eaten at least one time per week were identified, and percentages of
      participants consuming that frequency were calculated. Major food sources
      included: salad oil/cooking oil for calories, total fat and saturated fat;
      miscellaneous vegetables for dietary fiber and folate; and orange/grapefruit
      juice for vitamin C. Heterogeneity in food sources was greatest for zinc and
      least for vitamin C. Variation across gender and ethnic groups was observed only
      in the degree to which specific food sources contributed to nutrient intake.
      These data provide greater insight into the dietary patterns of rural elders than
      examining nutrient intakes.

PMID- 14714679
TI  - Tailoring of nutritional support for older adults in the community.
AB  - A study in Ontario, Canada of 137 elderly home delivered meal recipients, 90
      women and 47 men, confirmed the expected nutritional risk factors of living
      situation, functionality, morbidity and medication use. They were more pronounced
      among women than men. Seven-day food records showed energy intakes below the
      average for healthy Canadians of a similar age and gender. The probability of
      nutritional risk was highest for calcium, magnesium, zinc and folate with some
      gender differences, except for folate. While home delivered meals, if fully
      utilized, can provide considerable nutrition support, energy/nutrient
      inadequacies may persist among recipients unable to complement the meal
      appropriately. These older adults may require diet counseling and additional
      support including targeted nutritional supplementation.

PMID- 14714680
TI  - Differences in preferences of entrees by elderly congregate meal participants
      according to age, gender, ethnicity and education and a factor analysis approach
      to group entree preferences.
AB  - Congregate meal participants (n = 381), ages 60-100, provided preference ratings
      of 43 entrees utilizing a modified Food Rating Scale (FACT). Differences in
      preferences of entrees associated with age, gender, ethnicity and educational
      level were analyzed using X2 analysis. Factor analysis was used to group entrees
      which were associated according to preferences. Both males and females agreed
      with the top five preferred entrees. For other entrees, females had a higher
      acceptance level. Both age groups preferred the same top five entrees; for other
      entrees, the younger group was more accepting of these. Few differences were
      noted among the various ethnic groups (91% white and 7% African-American).
      Education level of respondents had a varying association with entree preference,
      depending upon the specific entree.

PMID- 14714681
TI  - Concepts, theories and design components for nutrition education programs aimed
      at older adults.
AB  - This article examines characteristics of older adult learners and discusses adult
      education theory and empowerment concepts, along with nutrition education and
      behavioral change strategies for older adult nutrition education programs. Design
      components for older adult nutrition education programs are presented.
      Educational and behavioral change strategies should be selected based on
      characteristics of the intended audience, including their nutrition needs, wants
      and desires, and should be based on appropriate theory. Multi-disciplinary
      research is needed to develop behavioral and educational theoretical frameworks,
      as well as designs, intervention strategies, and evaluation methods for
      educational programs that lead to older adults adopting more healthful nutrition
      practices. This is one of a series of recent literature reviews on nutrition
      education for older adults.

PMID- 14714682
TI  - Assessing nutrition education wants and needs of older adults through focus
      groups.
AB  - Five focus groups assessed the nutrition education wants and needs of 37 non
      institutionalized older adults ages 60 and older. Discussions were tape-recorded,
      transcribed and coded to facilitate data analysis. Findings cited most frequently
      included; doctors were influential, nutrition contributed to good health, basic
      nutrition topics were wanted/needed, written materials were used most often,
      demonstration and discussion methods were prevalently used/wanted, and service
      providers were primarily informed directly about wants/needs. Older adults
      wanted/needed nutrition education to improve their health and make informed
      decisions, and because the topic interested them. Information obtained could be
      used to develop more focused nutrition education programs for older adults.

PMID- 14714683
TI  - Patenting life forms: yesterday, today, and tomorrow.

PMID- 14714684
TI  - The evolution of gene patents viewed from the United States Patent Office.
AB  - In my remarks here, I have necessarily limited myself to general principles of
      patent law that are applicable to a consideration of gene-related inventions.
      Were I still Commissioner of Patents and Trademarks, I would not let electrical
      engineers anywhere near the examination of applications for patents for gene
      related inventions, just as I would not let the USPTO's many Ph.D.s in
      microbiology or genetics near the examination of complex applications on computer
      architecture or programming. The same should hold true for attorneys who
      prosecute patent applications. That is why the U.S. patent system works so well.
      There can be no discrimination in the system by the field of technology--a
      principle enshrined in Article 27 of the World Trade Organization's Trade-Related
      Aspects of Intellectual Property. But we quite properly depend upon specialists
      to apply across-the-board general principles to very specialized technological
      fields of endeavor. This works very well in a system in which in the U.S.,
      "everything under the sun made by humans" is patentable.

PMID- 14714685
TI  - Competition policy in patent cases and antitrust.
AB  - The article that follows examines the competition policy reflected in the
      decisions of the Court of Appeals for the Federal Circuit in its patent cases.
      The court's views on this subject have been manifested most plainly in decisions
      that have transformed the law concerning infringement under the doctrine of
      equivalents and claim construction. In both categories, the court narrowed patent
      scope by reason of its desire to protect competitors. The article argues that the
      court's premise in prescribing narrower claim scope reflected an incomplete view
      of competition policy. The court's analysis overlooked the benefits to
      competition provided by patents, which stimulate inventions and their
      development. The article traces the development of antitrust jurisprudence and
      demonstrates how respect for the contribution of patents to competition and
      skepticism of free-riding has evolved, particularly beginning in the 1970s. The
      article draws a parallel between the Court's reasoning about competition policy,
      on the one hand, and the rejected views of Justices Hugo Black and William O.
      Douglas and abandoned patent-antitrust jurisprudence, on the other. The Federal
      Circuit's decision in Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd.,
      234 F.3d 558 (Fed. Cir. 2000), on the subject of equivalents is considered in the
      paper. In that decision, the majority adopted a new rule that completely barred
      infringement under the doctrine of equivalents of any claim limitation where, in
      prosecution, there had been a narrowing amendment relating to patentability. In
      the past, prosecution estoppel foreclosing equivalents had been subject to a
      "flexible bar," which, in some circumstances, allowed for equivalence
      notwithstanding such an amendment. The article points out that because almost all
      patents are amended during prosecution, the effect would be to allow widespread
      copying of patented inventions by trivial modifications of any narrowed claim
      limitation. The incentive to innovate in the future would be correspondingly
      diminished and the expectations of past patentees would be correspondingly
      altered.

PMID- 14714686
TI  - Product patents on human DNA sequences: an obstacle for implementing the EU
      Biotech Directive?

PMID- 14714687
TI  - Patenting genetic products and processes: a TRIPS perspective.

PMID- 14714688
TI  - Enclosing the genome: what squabbles over genetic patents could teach us.

PMID- 14714689
TI  - Perusing property rights in DNA.
AB  - Many practical questions have arisen since the use of patents relating to DNA has
      become progressively more common after the landmark case of Diamond v.
      Chakrabarty in 1980: What ownership rights do patents confer? What is owned? Who
      owns it? What does ownership mean to nonoweners? The central theme of the chapter
      is that much of the debate about patent rights relating to DNA is needlessly
      burdened by concerns that are inapposite, given an informed understanding of how
      things actually work in this area; and that as a result, insufficient attention
      is paid to exploring propositions that might elucidate or even alleviate
      pertinent problems in need of solutions. The approach of the chapter is more
      analytical than prescriptive. It endeavors to unpack how property rights in this
      area actually operate and concludes by making a few modest prescriptions about
      areas for future study, including efforts to explore the mechanisms that might be
      at play when actual transactions in basic biological materials and protocols
      break down. The intuition behind the chapter is that although many of the
      problems identified by patent critics do exist and, in theory, might be
      pernicious in creating some inefficiency in the form of dead-weight loss, in
      practice these problems turn out to be less pernicious than those likely to be
      caused by alternative regimes and are mitigated through various behaviors of
      market participants.

PMID- 14714690
TI  - Steady the course: property rights in genetic material.

PMID- 14714691
TI  - Varying the course in patenting genetic material: a counter-proposal to Richard
      Epstein's steady course.

PMID- 14714692
TI  - Reaching through the genome.
AB  - Advances in genomics research have called forth new strategies for patenting DNA
      sequences. Gene patenting, which began inconspicuously in the early days of the
      biotechnology industry in the 1970s and 1980s, did not generate significant
      public controversy until the advent of high-throughput DNA sequencing in the
      1990s. By this point, it was such a well-established practice that categorical
      challenges to the patentability of DNA seemed quaint and out of touch. Yet
      something was plainly different. In the early days, patenting genes looked like
      patenting drugs. By the early 1990s, it looked more like patenting scientific
      information. We have a reasonably clear story about why we should issue patents
      on drugs; the case for issuing patents on scientific information is less clear.
      Patents on research discoveries arising far upstream from end-product development
      threaten the interests of research scientists, who fear impediments to the free
      use and dissemination of new discoveries, and of downstream product developers,
      who fear that they will be foreclosed from pursuing certain research and
      development (R&D) pathways or that their profits will be diluted by the claims of
      upstream predecessors. At the same time, it is not obvious how upstream patent
      owners might use patents to capture the value that their discoveries contribute
      to downstream product development, particularly in the face of concerted
      resistance to sharing the wealth. This strategic challenge is leading upstream
      innovators to pursue novel patent claiming and licensing approaches that raise
      unresolved doctrinal and policy questions.

PMID- 14714693
TI  - The Human Genome Project in retrospect.

PMID- 14714694
TI  - Goat-boy roams the halls?

PMID- 14714695
TI  - Comment on the tragedy of the anticommons in biomedical research.

PMID- 14714696
TI  - An outsider perspective on intellectual property discourse.

PMID- 14714697
TI  - Saving the patent law from itself: informal remarks concerning the systemic
      problems afflicting developed intellectual property regimes.

PMID- 14714698
TI  - Biotechnology's uncertainty principle.

PMID- 14714699
TI  - Commentary on the panel presentations.

PMID- 14714700
TI  - (Mostly) against exceptionalism.

PMID- 14714701
TI  - Brave new industry, that has such patents in it! Reflections on the economic
      consequences of patenting DNA.

PMID- 14714702
TI  - Pharmacogenomics, genetic tests, and patent-based incentives.
AB  - Pharmacogenomics promises to revolutionize medicine by using genetic information
      to guide drug therapy. Genetic tests should help doctors improve drug safety and
      efficacy by better matching patients and drugs. This chapter evaluates the
      effectiveness of patent-based incentives to create genetic tests, and considers
      the optimal mix of public and private sector pharmacogenomic research and
      development (R&D). Drug patent owners have a strong incentive to develop genetic
      tests that predict adverse drug reactions and allow them to market drugs that
      otherwise would be shelved. Incentives are also strong for genetic tests that are
      created as part of the drug development process. Incentives tend to be weaker for
      genetic tests that are used in conjunction with existing drugs. Drug patent
      owners might gain or lose profit from the introduction of genetic tests into
      existing drug markets. Profits may fall because of lost sales, or profits may
      rise because drugs are more valuable to appropriate patients, and because drugs
      become more differentiated. Public sector R&D should target genetic tests that
      are likely to be underprovided by the private sector because private returns are
      low relative to social returns, or private costs are high relative to social
      costs. Private returns are relatively low when the rate of adoption of a genetic
      test is apt to be low, when test results increase consumer heterogeneity and
      consumer bargaining power, and when a test reveals information relevant to the
      use of more than one drug. Private costs are relatively high when test innovators
      need to obtain costly patent and trade secret licenses.

PMID- 14714703
TI  - The effect of intellectual property on the biotechnology industry.

PMID- 14714704
TI  - Are real business people so easily thwarted?

PMID- 14714705
TI  - One size fits all?

PMID- 14714706
TI  - Some empirical evidence on how technologically complex issues are decided in
      patent cases in U.S. District Courts.

PMID- 14714707
TI  - How ordinary judges and juries decide the seemingly complex technological
      questions of patentability over the prior art.
AB  - Determinations of patentability over the prior art are often thought to raise
      questions that are so technologically complex that they require special training
      and judgment to answer, especially in fast-moving fields like modern
      biotechnology. This essay explores the somewhat counterintuitive argument that
      under the U.S. system they do not and should not. According to this view,
      determinations of patentability over the prior art are based entirely on factual
      inquiries that are best made by lay judges and juries, just like the factual
      determinations these people regularly make in any ordinary nonpatent trial. This
      is good because judges and juries are adept at these determinations, and because
      appellate courts are adept at reviewing them. It leads to a system that is
      cheaper overall in allowing private litigants to better predict outcomes that
      also better approximate the correct answer than would be possible under other
      regimes premised upon the expert technological knowledge and judgment of a
      decisionmaker.

PMID- 14714708
TI  - The difficult interface: relations between the :sciences and the law.

PMID- 14714709
TI  - Early 18th century French obstetric textbook.

PMID- 14714710
TI  - Genomics in obstetrics and gynaecology.
AB  - With the Human Genome Project complete, and microarray technology progressing
      rapidly, the study of whole genomes has become a reality. The emerging field of
      genomics is full of promise, has become a cornerstone of commercial drug
      development, and looks certain to make a major contribution to clinical practice
      in the future. There is an increasing number of genomic studies concerned with
      obstetric and gynaecological conditions. Despite this, clinicians in their busy
      practices often lack a basic understanding of genomics and the tools involved in
      generating genome-based information. In the present review, we aim to provide the
      clinician with a basic overview of genomics--what it is, what tools it uses, and
      how it may benefit our patients. The existing published reports on genomic
      studies in the reproductive field is reviewed.

PMID- 14714711
TI  - Revised key messages for hormone replacement therapy from the New Zealand
      Guidelines Group.
AB  - The publication of the Women's Health Initiative Study in 2002 has led to changes
      in the advice for women considering hormone replacement therapy (HRT) use. Along
      with other organisations worldwide, the New Zealand Guidelines Group (NZGG)
      revised their key messages for the appropriate prescribing of HRT. Long-term HRT
      use was not recommended, nor was the use of HRT for the prevention of coronary
      heart disease and stroke. While acknowledging the effectiveness of HRT for relief
      of menopausal symptoms, the group felt that women needed to be informed of the
      potential risks. Methodological criticisms of Women's Health Initiative (WHI) are
      discussed along with suggestions of how the study findings may be used for
      individual decision-making. In addition to presenting the new advice from the
      NZGG, the present paper compares these findings with other international bodies
      and seeks to present some consensus that may help decision-making for women who
      are symptomatic at menopause.

PMID- 14714712
TI  - Clinical aspects of gestational trophoblastic disease: a review based partly on
      25-year experience of a statewide registry.
AB  - BACKGROUND: Gestational trophoblastic disease is a fascinating group of pregnancy
      disorders characterised by abnormal proliferation of trophoblast, ranging from
      benign to malignant. Because the disease is uncommon, there is a need to
      formulate management with the assistance of collective information. METHODOLOGY:
      A review of available information from English written literature was undertaken,
      especially data reported by registries around the world (Charing Cross Hospital
      in England, the North-western University and the New England area in the USA as
      well as our own experience in Queensland, Australia). Where possible, collated
      data from relevant studies were analysed to answer some of the questions posed in
      clinical practice, with reference to metastatic disease to liver and brain,
      twinning of molar gestation and coexisting fetus, and placental-site tumour.
      RESULTS: We found that molar gestation can be classified according to its
      clinical presentation which influences the time taken to reach human chorionic
      gonadotropin (HCG) 'negativity' and the risk of persisting disease.
      Categorisation of risk is the basis for choice of chemotherapy to achieve good
      outcomes. Metastases to liver and brain remain problems in management; the
      development of 'new' metastases during chemotherapy is a very poor prognostic
      factor. In the variant of twinning with molar gestation and coexisting fetus, it
      is important to elucidate the fetal karyotype in planning management: a 69XXX
      fetus is not salvageable but a normal 46XX or 46XY fetus faces the prospect of
      early preterm delivery. The placental-site tumour is very rare; localised disease
      is curable by surgery; chemotherapy is less effective in disseminated disease.
      From collated worldwide data, the recurrence rate after one mole is 1.3% and
      after two or more is 20%. Reproductive outcome in subsequent pregnancies, even
      after multidrug chemotherapy, is not different from the general population.
      Because of the increased risk long-term of second tumours after multidrug
      chemotherapy a closer surveillance of these patients is necessary. CONCLUSION: In
      general, the disease in its persisting or malignant form is 'a cancer model par
      excellence' because of an identifiable precursor condition, a reliable HCG
      marker, and sensitivity of the disease to cytotoxic drugs. With current
      management, retention of fertility is possible and normal reproductive outcome
      assured.

PMID- 14714713
TI  - Hepatitis C and pregnancy: an update.
AB  - Hepatitis C is a slowly progressive disease with significant long-term sequelae
      including cirrhosis, liver failure and hepatocellular carcinoma. Many women of
      childbearing years are infected with this virus and are at risk of transmitting
      it to their offspring. Despite this, there are many unanswered questions about
      hepatitis C and pregnancy including who to screen, the risk factors associated
      with infection, how these women should be managed during pregnancy and the
      options available to them after delivery.

PMID- 14714714
TI  - The management of breech pregnancies in Australia and New Zealand.
AB  - AIM: To assess current obstetric practice in the management of singleton breech
      pregnancies in Australia and New Zealand. METHODOLOGY: Survey mailed to all
      members and fellows of the Royal Australian and New Zealand College of Obstetrics
      and Gynaecology. RESULTS: Of 1284 surveyed, 956 (74%) responded of whom 696 (73%)
      were practicing obstetrics. Prior to the Term Breech Trial (TBT), 72% of
      obstetricians reported that they routinely offered vaginal breech birth for
      uncomplicated singleton breech pregnancies. After the TBT publication this rate
      declined to 20%. External cephalic version (ECV) was usually recommended by 67%
      of obstetricians and only 53% use tocolytics. Common practices for which safety
      has yet to be demonstrated included 28% of obstetricians carrying out ECV outside
      hospitals and 42% carrying out ECV before 37 weeks' gestation. CONCLUSIONS: While
      the majority of obstetricians recommend ECV and/or planned Caesarean section for
      breech presentation, barriers to the promotion of ECV and the use of tocolysis
      for ECV need to be identified if the rates of this effective manoeuvre are to be
      increased.

PMID- 14714715
TI  - Caesarean for breech: a paradigm shift?
AB  - The year 2001 became 'the year of Caesarean for the breech' after the results of
      the Term Breech Trial were published in October 2000. The purpose of the current
      paper is a retrospective observational study identifying the increase in
      Caesarean section rates that occurred in Fairfield Hospital after the Term Breech
      Trial. Fairfield Hospital is a level 2 hospital in the south-western Sydney
      health area with 1800 deliveries per year.

PMID- 14714716
TI  - Use of umbilical artery Doppler velocimetry in the monitoring of pregnancy in
      women with pre-existing diabetes.
AB  - BACKGROUND: The usefulness of umbilical artery Doppler velocimetry for the
      monitoring of diabetic pregnancies is controversial. The aim of the present study
      was to assess whether umbilical artery Doppler velocity waveform analysis can
      predict adverse perinatal outcomes for pregnancies complicated by pre-existing
      diabetes mellitus. METHODS: All diabetic pregnancies (type 1 and 2) delivered at
      Mater Mothers' Hospital, Queensland, between 1 January 1995 and 31 December 1999
      were included. All pregnant diabetic women were monitored with umbilical artery
      Doppler velocimetry at 28, 32, 36, and 38 weeks' gestation. Adverse perinatal
      outcome was defined as pregnancies with one or more of the following: small-for
      gestational age, Caesarean section for non-reassuring cardiotocography, fetal
      acidaemia at delivery, 1-min Apgar of 3 or less, 5-min Apgar of less than 7,
      hypoxic ischaemic encephalopathy or perinatal death. Abnormal umbilical artery
      Doppler velocimetry was defined as a pulsatility index of 95th centile or higher
      for gestation. RESULTS: One hundred and four pregnancies in women with pre
      existing diabetes had umbilical arterial Doppler studies carried out during the
      study period. Twenty-three pregnancies (22.1%) had an elevated pulsatility index.
      If the scans were carried out within 2 weeks of delivery, 71% of pregnancies with
      abnormal umbilical Doppler had adverse outcomes (P < 0.01; likelihood ratio,
      4.2). However, the sensitivity was 35%; specificity was 94%; positive predictive
      value was 80%; and negative predictive value was 68%. Only 30% of women with
      adverse perinatal outcomes had abnormal umbilical arterial Doppler flow.
      CONCLUSION: Umbilical artery Doppler velocimetry is not a good predictor of
      adverse perinatal outcomes in diabetic pregnancies.

PMID- 14714717
TI  - Prenatal screening and diagnosis: a survey of health care providers' knowledge
      and attitudes.
AB  - AIM: To survey the knowledge and attitudes of health care providers in Western
      Australia, Australia towards prenatal screening and diagnostic procedures for
      fetal anomalies. DESIGN: A self-administered mail survey. SAMPLE: 30
      obstetricians and 313 general practitioners (GPs). RESULTS: Overall, relative to
      GPs, obstetricians expressed more positive attitudes towards prenatal tests.
      Moreover, GPs felt they had a greater need for additional information. Further
      group differences were found in attitudes towards the value of the tests and
      confidence in the availability and ease of coordination of follow-up services
      according to geographical area. Female health care providers were significantly
      more confident about the availability of follow-up services and had higher
      knowledge scores. They were also more likely to practice in the metropolitan
      area. Further group differences were found in attitudes according to
      participation in professional development. CONCLUSION: Overall, health care
      providers felt antenatal screening and diagnostic tests were valuable and they
      felt they could benefit from further information. Knowledge was high, however, it
      is unclear whether this knowledge is being communicated to women. Given that
      antenatal practices are rapidly evolving, continuing education and ongoing
      professional development is critical.

PMID- 14714718
TI  - Identification of yeasts in public hospital primary care patients with or without
      clinical vaginitis.
AB  - OBJECTIVE: Vaginal yeast infections are one of the most common female genital
      tract infections. Candida albicans is the most common infectious cause. Candida
      species other than C. albicans are being diagnosed with increasing frequency. The
      aim of the present study was to determine species of yeasts obtained from the
      vaginal fluid among public hospital primary care patients with or without
      clinical vaginitis and to evaluate the correlation of vaginal yeast colonisation
      with epidemiological and clinical features of applicants. METHODS: Vaginal swabs
      from 622 women who underwent vaginal examination in a women's hospital were
      obtained. After isolation, identification tests were carried out on 106 yeast
      species. Epidemiological and clinical features of women with respect to these
      species were evaluated. RESULTS: Of 106 yeasts isolated, 67 C. albicans, 10 C.
      glabrata, seven C. kefyr (pseudotropicalis), six C. tropicalis, five C.
      parapsilosis, five C. krusei, three Saccharomyces boulardii, one C.
      guillermondii, one S. cerevisiae and one Trichosporon species were identified as
      yeast subtypes. Of the women with C. albicans, C. glabrata, C. kefyr, C.
      tropicalis, C. krusei, 60, three, one, one, and one, respectively, had symptoms
      of vaginitis. Of women with C. albicans, C. glabrata, C. kefyr, C. tropicalis, C.
      parapsilosis, C. krusei, and the other species, 27, four, three, two, one, one,
      and one, respectively, had clinical findings of vaginitis. CONCLUSION: Despite
      the heterogeneity of the present study group, the results support the use of
      vaginal culture as the most sensitive test for final diagnosis. However, a
      positive culture does not mean that the C. albicans is pathogenic, as it may be
      the normal commensal pathogen. Correlation of clinical and laboratory findings is
      important as it enables the administration of appropriate treatment without
      delay.

PMID- 14714719
TI  - Preterm birth a long distance from home and its significant social and financial
      stress.
AB  - The present paper reports a retrospective cohort of preterm infants admitted to
      our hospital who delivered outside the normal geographical catchment area of the
      mother's local level three neonatal nursery. Nineteen mothers had 21 preterm
      infants (23.1-34.9 weeks, 500-2330 g born) where 14 infants required ventilation
      (median 57 h, range 3-428). Eighteen survivors had a median length of stay of 41
      days (range 3-91). Twelve of 19 mothers were interviewed: all described
      isolation, loneliness, poor social support and significant financial hardship
      related to getting their infants back to a local hospital or home. To avoid these
      problems, we recommend confining travel to within a short distance from home or
      local maternity unit after 22 weeks.

PMID- 14714720
TI  - Minor vestibular gland adenoma: a case report.

PMID- 14714721
TI  - Pain mapping, awake laparoscopy and chronic pelvic pain.

PMID- 14714722
TI  - Atypical leiomyoma of the broad ligament.

PMID- 14714723
TI  - Unusually elevated serum carbohydrate antigen 125 (CA125) and CA19-9 levels as a
      result of unruptured bilateral endometrioma.

PMID- 14714724
TI  - Intestinal leiomyoma presenting as a pelvic mass: two case reports.

PMID- 14714725
TI  - Placenta percreta causing spontaneous uterine rupture in late pregnancy:
      conservative surgical management.

PMID- 14714726
TI  - Biochemical and pharmacological aspects of two bradykinin-potentiating peptides
      obtained from tryptic hydrolysis of casein.
AB  - Peptides that display bradykinin-potentiating activity have been obtained from a
      number of distinct sources, such as snake venoms, fibrinogen, and casein. This
      paper describes the characterization of two new peptides generated by tryptic
      hydrolysis of casein. No homology was found with other known vasoactive or
      vasopotentiating peptides, especially by the lack of Ile-Pro-Pro motif. The
      peptides EMPFPK and YPVEPFTE, corresponding to the gamma casein sequence (108-113
      and 114-121, respectively), displayed a selective potentiating activity on
      isolated guinea pig ileum for bradykinin. Besides, the octapeptide YPVEPFTE
      showed an in vitro competitive inhibitor effect on angiotensin-converting enzyme
      and thimet oligopeptidase and presented an opiate-like activity, increasing two
      times the latence time in the hot-plate assay. The results suggest that the
      isolated bioactive peptides act on conversion and/or inactivation of endogenous
      peptides by enzymes such as angiotensin-converting enzyme and thimet
      oligopeptidase by modifying several systemic responses such as blood-pressure
      regulation and in pain response.

PMID- 14714728
TI  - Effect of thiohydroxyl compounds on tyrosinase: inactivation and reactivation
      study.
AB  - An unusual thioether bridge (Cys-His) has been detected at the active site of
      mushroom tyrosinase, and the effects of thiohydroxyl compounds such as
      dithiothreitol (DTT) and beta-mercaptoethanol (beta-ME) on Cu2+ at the active
      site have been elucidated. Treatment with DTT and beta-ME on mushroom tyrosinase
      completely inactivated 3,4-dihydroxyphenylalanine oxidase activity in a dose
      dependent manner. Sequential kinetic studies revealed that DTT and beta-ME caused
      different mixed-type inhibition mechanisms: the slope-parabolic competitive
      inhibition (Ki = 0.143 mM) by DTT and slope-hyperbolic noncompetitive inhibition
      (Ki = 0.0128 mM) by beta-ME, respectively. Kinetic Scatchard analysis
      consistently showed that mushroom tyrosinase had multiple binding sites for DTT
      and beta-ME with different affinities. Reactivation study of inactivated enzyme
      by addition of Cu2+ confirmed that DTT and beta-ME directly bound with Cu2+ at
      the active site. Our results may provide useful information regarding
      interactions of tyrosinase inhibitor for designing an effective whitening agent
      targeted to the tyrosinase active site.

PMID- 14714727
TI  - Inhibitory effect of 4-cyanobenzaldehyde and 4-cyanobenzoic acid on mushroom
      (Agaricus bisporus) tyrosinase.
AB  - Mushroom tyrosinase (EC 1.14.18.1), a copper containing oxidase, catalyzes both
      the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols
      into o-quinones. In the current study, the effects of 4-cyanobenzaldehyde and 4
      cyanobenzoic acid on the monophenolase and diphenolase activities of mushroom
      tyrosinase have been studied. The results show that 4-cyanobenzaldehyde and 4
      cyanobenzoic acid can inhibit both the monophenolase activity and the diphenolase
      activity of mushroom tyrosinase. The lag phase of tyrosine oxidation catalyzed by
      the enzyme was obviously lengthened, and the steady-state activity of the enzyme
      decreased sharply. 1.0 mM 4-cyanobenzaldehyde and 4-cyanobenzoic acid can
      lengthen the lag phase from 78 s to 134 and 115 s, respectively. Both 4
      cyanobenzaldehyde and 4-cyanobenzoic acid can lead to reversible inhibition of
      the enzyme. The IC50 values of 4-cyanobenzaldehyde and 4-cyanobenzoic acid were
      estimated as 0.62 and 2.45 mM for monophenolase and as 0.72 and 1.40 mM for
      diphenolase, respectively. A kinetic analysis shows that 4-cyanobenzaldehyde and
      4-cyanobenzoic acid are mixed-type inhibitors for the diphenolase. The apparent
      inhibition constants for 4-cyanobenzaldehyde and 4-cyanobenzoic acid binding with
      both the free enzyme and the enzyme-substrate complex have been determined and
      compared.

PMID- 14714729
TI  - Oncogenic and activated wild-type ras-p21 proteins induce different isoforms of
      protein kinase C in mitogenic signal transduction.
AB  - We have previously found that the protein kinase C (PKC) inhibitor, CGP 41 251,
      blocks oncogenic ras-p21 protein- and beta-PKC-induced oocyte maturation, but
      only weakly inhibits insulin-induced oocyte maturation (which requires activation
      of wild-type endogenous ras-p21). Because the dose-response curves for inhibition
      of oncogenic p21- and beta-PKC-induced oocyte maturation by CGP 41 251
      superimpose and because the ras-p21-inactivating antibody, Y13-259, does not
      inhibit beta-PKC-induced oocyte maturation, we concluded that the oncogenic, but
      not wild-type, protein requires beta-PKC as a downstream target. Because multiple
      isoforms of PKC exist and several of these, such as epsilon-PKC, have been found
      to be important on ras signal transduction pathways, we have investigated which
      PKC isoforms are critical to each ras protein. For this purpose, we used PKC
      isoform-specific inhibitors, which have been shown to inhibit selectively the
      function and translocation of PKC isoforms in vitro and in vivo. Specifically,
      the peptides KLFIMN, QEVIRN, and EAVSLKPT each inhibit beta-1, beta-2, and
      epsilon-PKC, respectively, but do not cross-inhibit other PKC isoforms. We find
      that the epsilon-PKC inhibitory peptide strongly blocks insulin- but not
      oncogenic ras-p21-induced oocyte maturation whereas the beta-2 inhibitory peptide
      more strongly inhibits oncogenic ras-p21-induced oocyte maturation, corroborating
      our previous studies. The beta-1 inhibitory peptide has little effect on either
      protein. We conclude that selective inhibition of individual PKC isoforms permits
      the distinction between signal transduction initiated by oncogenic and activated
      wild-type p21 proteins and implicate different specific PKC isoforms in mitogenic
      signal transduction by each of these proteins. The ability to dissect the role of
      individual PKC isozymes in this regulation is of therapeutic significance.

PMID- 14714730
TI  - Arylamine N-acetyltransferases: covalent modification and inactivation of hamster
      NAT1 by bromoacetamido derivatives of aniline and 2-aminofluorene.
AB  - Kinetic analysis of the inactiviation of hamster NAT1 by 2
      (bromoacetylamino)fluorene (Br-AAF) and bromoacetanilide revealed that Br-AAF is
      an active site directed affinity label whereas bromoacetanilide acts as a
      bimolecular alkylating agent. ESI MS analysis of NAT1 treated with Br-AAF showed
      that a single molecule of 2-acetylaminofluorene had been incorporated.
      Proteolysis with pepsin followed by sequencing of adducted peptides by ESI MS/MS
      identified the modified residue as the catalytically essential Cys-68. ESI Q-TOF
      MS analysis of NAT1 that had been treated with bromoacetanilide resulted in
      identification of a monoadducted protein as the primary product and a diadducted
      protein as a minor product. Pepsin digestion of bromoacetanilide-inactivated NAT1
      and sequencing by ESI MS/MS identified Cys-68 as the primary site of adduct
      formation. Additional proteolysis of the bromoacetanilide-treated NAT1 led to the
      identification of a second modified peptide which was adducted at Cys-44. The
      data reveal substantial differences in the interactions of small hydrophobic
      alkylating reagents with hamster NAT1.

PMID- 14714731
TI  - The structural and functional studies of His119 and His12 in RNase A via chemical
      modification.
AB  - The histidyl residues of bovine pancreatic ribonuclease A (RNase A) play a
      crucial role in enzymatic activity. Diethylpyrocarbonate (DEPC) is a potent
      inhibitor of RNase A, and its precise sites of action on the imidazole rings of
      the four histidyl residues of RNase A are not clearly defined. We have used a
      multidisciplinary approach including enzyme assay, calculation of accessible
      surface area (ASA), isoelectric pH gradient technique, fluorescence
      investigations, circular dichroism spectroscopy, differential scanning
      calorimetry, and 1H NMR analysis to study the sites of DEPC interaction with the
      imidazole rings of the four histidyl residues. Our results demonstrate that among
      the histidyl residues of RNase A, His48 is not accessible to react with DEPC.
      However, the sequential carbethoxylation of the imidazole rings of His119,
      His105, and His12 occurs on the nitrogen atoms of Ndelta, Nepsilon, and Nepsilon,
      respectively. Carbethoxylation of His119 was followed by conversion of the A
      conformation to the B conformation in the active site. However, the
      carbethoxylation of His12 was accompanied by a second spatial rotation of the
      corresponding imidazole ring in the active site to adopt a new conformation.
      These conformation changes are accompanied by subsequent decrements in the
      thermal stability of the protein. Therefore, these findings reinforce the
      important structural roles of the spatial positions for His119 and His12 in the
      active site of RNase A.

PMID- 14714732
TI  - Isolation and characterization of a lectin from Annona muricata seeds.
AB  - A lectin with a high affinity for glucose/mannose was isolated from Annona
      muricata seeds (Annonaceae) by gel filtration chromatography on Sephacryl S-200,
      ion exchange chromatography on a DEAE SP-5 PW column, and molecular exclusion on
      a Protein Pak Glass 300 SW column. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (PAGE) yielded two protein bands of approximately 14 kDa and 22
      kDa. However, only one band was seen in native PAGE. The Mr of the lectin
      estimated by fast-performance liquid chromatography-gel filtration on Superdex 75
      was 22 kDa. The lectin was a glycoprotein with 8% carbohydrate (neutral sugar)
      and required divalent metal cations (Ca2+, Mg2+, and Mn2+) for full activity.
      Amino acid analysis revealed a large content of Glx, Gly, Phe, and Lys. The
      lectin agglutinated dog, chicken, horse, goose, and human erythrocytes and
      inhibited the growth of the fungi Fusarium oxysporum, Fusarium solani, and
      Colletotrichum musae.

PMID- 14714733
TI  - Beta-galactosidases (Escherichia coli) with double substitutions show that Tyr
      503 acts independently of Glu-461 but cooperatively with Glu-537.
AB  - Beta-galactosidases with single substitutions for Tyr-503, Glu-461, and Glu-537
      and with double substitutions for Tyr-503 and either Glu-461 or Glu-537 were
      constructed. Control experiments showed that the very low kcat values obtained
      for the double-substituted enzymes were not a result of contamination, reversion,
      or nonactive site activity catalyzed on the surface of the proteins. Circular
      dichroism studies showed that the structures of the enzymes were intact.
      E461Q/Y503F-beta-galactosidase was inactivated in an "additive" manner. This
      indicated that Glu-461 and Tyr-503 act independently in catalysis. Because these
      residues are at opposite sides of the active site and act in different steps,
      this is expected. E537D/Y503F-beta-galactosidase was only inactivated a few-fold
      more than the most inactive of its two single-substituted constituent beta
      galactosidases. This showed that Glu-537 and Tyr-503 interact cooperatively on
      the same step. This correlates well with the proposed role of Tyr-503 as an acid
      catalyst for the breakage of the covalent bond between Glu-537 and galactose.

PMID- 14714734
TI  - Trichloroacetic acid-induced molten globule state of aminoacylase from pig
      kidney.
AB  - The trichloroacetic acid (TCA)-induced unfolding of aminoacylase was investigated
      by measurement of aggregation, enzyme activity, intrinsic fluorescence, 8-anilino
      1-naphthalene sulfonate (ANS) binding, circular dichroism, and native
      polyacrylamide gel electrophoresis. The results showed that TCA caused
      inactivation and unfolding of aminoacylase. Intrinsic fluorescence results
      demonstrated that the TCA-induced transition of aminoacylase was characterized by
      two distinct stages during which the fluorescence emission maxima first
      redshifted to 338 nm and then blueshifted to 332 nm, close to that of native
      protein. ANS binding measurements revealed that TCA-denatured aminoacylase had a
      large hydrophobic area for TCA concentration near 2 mM. Comparison of the
      relative changes in wavelength shift and in the ANS intensity suggested the
      formation of a stable molten globule state of aminoacylase with a slightly
      disrupted tertiary structure and more hydrophobic surface than the native
      protein. Far-UV circular dichroism results provided further support that TCA
      induced the formation of two partially folded intermediates each with an enhanced
      native-like secondary structure. The results collectively suggest that a TCA
      induced molten globule state is formed and stabilized during unfolding of
      aminoacylase and that association of the molten globule state may account for
      precipitation of the protein when denatured by TCA.

PMID- 14714735
TI  - Effect of ethylene glycol and polyethylene glycol on the acid-unfolded state of
      trypsinogen.
AB  - Effect of increasing concentrations of two of the polyols, ethylene glycol (EG)
      and polyethylene glycol (PEG), was studied by near and far circular dichroism
      (CD), fluorescence emission spectroscopy, and binding of hydrophobic dye, 1
      anilino-8-naphthalene sulfonic acid (ANS). Far-UV CD spectra show the transition
      of acid-unfolded trypsinogen from an unordered state to an intermediate state
      having ordered secondary structure. Interestingly, near-UV CD spectra show some
      amounts of stabilizing effect on the tertiary structure of the protein also.
      Tryptophan fluorescence studies indicate the change in the environment of the
      tryptophan residues on addition of EG and PEG. Maximum ANS binding occurs in
      presence of 80% EG and 90% PEG (v/v), suggesting the presence of an intermediate
      or molten globule-like state at high concentrations of the two polyols.

PMID- 14714736
TI  - The cDNA-derived amino acid sequence of hemoglobin II from Lucina pectinata.
AB  - Hemoglobin II from the clam Lucina pectinata is an oxygen-reactive protein with a
      unique structural organization in the heme pocket involving residues Gln65 (E7),
      Tyr30 (B10), Phe44 (CD1), and Phe69 (E11). We employed the reverse transcriptase
      polymerase chain reaction (RT-PCR) and methods to synthesize various cDNA(HbII).
      An initial 300-bp cDNA clone was amplified from total RNA by RT-PCR using
      degenerate oligonucleotides. Gene-specific primers derived from the HbII-partial
      cDNA sequence were used to obtain the 5' and 3' ends of the cDNA by RACE. The
      length of the HbII cDNA, estimated from overlapping clones, was approximately
      2114 bases. Northern blot analysis revealed that the mRNA size of HbII agrees
      with the estimated size using cDNA data. The coding region of the full-length
      HbII cDNA codes for 151 amino acids. The calculated molecular weight of HbII,
      including the heme group and acetylated N-terminal residue, is 17,654.07 Da.

PMID- 14714737
TI  - Aetiology and prevalence of canine anaemia in Zaria: a review of 2139 cases
      observed at the Veterinary Teaching Hospital of the Ahmadu Bello University,
      Zaria, Nigeria (1990-2003).
AB  - An investigation was conducted at the Ahmadu Bello University Veterinary Teaching
      Hospital (ABUVTH) between January, 1990 and September, 2003 to determine the
      aetiology and prevalence of canine anaemia in Zaria, Nigeria. Out of the 5278
      mongrel dogs presented during the period 1990-2003, 2139 (40.5%) were found to be
      anaemic, with packed cell volume (PCV) values ranging from 7 to 36%. The clinical
      signs presented by these dogs include: Pale mucous membranes, weakness,
      depression, anorexia/inapettence and reduced activity. About 50 dogs (about 1%)
      with helminths and haemoparasitic infestations had high PCV values (37-40%)
      without clinical presentation of anaemia or disease. Most of the dogs with
      anaemia (n = 2016 or 94.2%) had parasitic infestations. About 1580 (about 74%) of
      the anaemic cases, attributed to parasitic infestations occurred between May and
      October. A few dogs (n = 55, 2.6%) had anaemia due to poor nutrition, while 68
      (3.2%) had anaemia with unknown cause. The public health significance of the
      parasites reported in this study is discussed.

PMID- 14714738
TI  - Pathogenesis and pathology of blackleg in ruminants: the role of toxins and
      neuraminidase. A short review.
AB  - There is no consensus on the pathogenesis of blackleg infection that occurs in
      ruminants, but toxins and neuraminidase produced by Clostridium chauvoei are
      believed to play a significant role in the pathogenesis of the disease. This
      paper provides an update on the role of toxins and neuraminidase in the
      pathogenesis and pathology of the disease. The use of neuraminidase inhibitors to
      manage clinical blackleg infections is therefore an alternative therapeutic
      protocol that should be thoroughly investigated. It is suggested that in vivo
      clinical trials should be carried out to determine the mechanism of action and
      clinical efficacy of neuraminidase inhibitors.

PMID- 14714739
TI  - First cases of animal diseases published since 2000. 4. Horses.
AB  - In this fourth article of a series of papers listing first case reports of animal
      diseases published since 2000, the following six cases of horse diseases are
      discussed: Disseminated metastatic intramedullary melanoma. Lipoma of the
      extensor tendon sheaths. Meningoencephalomyelitis in a neonatal foal due to
      Salmonella agona infection. Neuronal ceroid lipofuscinosis. Placentitis due to
      Rhodococcus equi infection. Right atrial diverticulum in a foal. After a short
      introduction, the bibliographical data, the abstract of the author(s), and some
      additional information derived from the article are given. The article will be
      regularly updated adding overlooked as well as new first reports.

PMID- 14714740
TI  - First cases of animal diseases published since 2000. 5. Sheep.
AB  - In this fifth article of a series of papers listing first case reports of animal
      diseases published since 2000, the following five cases of sheep diseases are
      discussed: Ependymoma. Mastitis caused by Burkholderia cepacia infection.
      Meningoencephalitis associated with Globicatella sanguinis infection. Neospora
      caninum infection in an adult sheep and her twin fetuses. Plasma cell tumor.
      After a short introduction, the bibliographical data, the abstract of the
      author(s), and some additional information derived from the article are given.
      The article will be regularly updated adding overlooked as well as new first
      reports.

PMID- 14714741
TI  - Borjeson-Forssman-Lehmann syndrome: a novel pituitary phenotype due to mutation
      in a novel gene.

PMID- 14714742
TI  - Preventable factors in childhood that lead to insulin resistance, diabetes
      mellitus and the metabolic syndrome: the EarlyBird diabetes study 1.
AB  - For a decade or more, poor nutrition during gestation, expressed as low weight at
      birth, was held to be the factor responsible for insulin resistance later in
      life. Birth weights, however, are rising and insulin resistant states, such as
      diabetes mellitus, faster still. Alternative explanations are needed to explain
      insulin resistance in contemporary industrialised populations. EarlyBird is a non
      intervention prospective cohort study that asks the question 'Which children
      develop insulin resistance, and why?' It is unique in taking serial blood samples
      from a young age with which to monitor the behaviour of insulin resistance and
      its metabolic correlates. This, the baseline report of the EarlyBird Study,
      describes the rationale, design and methodology of the study, and the profile of
      the population at entry. It situates the anthropometric, physical activity and
      dietary status of the EarlyBird children and provides a detailed metabolic
      profile of the British 5 year-old in the year 2000.

PMID- 14714743
TI  - Serum uric acid levels in obese children and adolescents: linkage to testosterone
      levels and pre-metabolic syndrome.
AB  - Hyperuricemia is part of the "metabolic syndrome". The aim of this study was to
      investigate the regulation and role of serum uric acid in the cardiovascular risk
      factor profile of obese children and adolescents. Serum levels of uric acid and
      selected risk factors and hormones were determined in 269 children aged 10.0-15.9
      years with a BMI >90th percentile (mean 24.0 kg/m2, SD 5.43). Stepwise regression
      adjusted for age and sex revealed that testosterone (p < 0.0001), BMI (p <
      0.0001), systolic blood pressure (p < 0.0017), triglycerides (p < 0.0345) and
      cholesterol/HDL ratio (p < 0.0393) were positively correlated with serum uric
      acid and accounted for 42.1% of the variance. Additional regression models with
      the same set of variables indicated that uric acid contributed significantly to
      levels of cholesterol/HDL, total cholesterol, BMI and systolic blood pressure,
      respectively. These results suggest a not yet described impact of androgens in
      the regulation of serum uric acid in obese children and adolescents. Furthermore,
      they show that uric acid is a reliable indicator for the "pre-metabolic syndrome"
      in obese youths.

PMID- 14714744
TI  - Birth characteristics and growth pattern in children with congenital
      cytomegalovirus infection.
AB  - Birth characteristics and growth pattern in 76 children with congenital
      cytomegalovirus (CMV) infection were compared to Swedish reference data.
      Infection classification was based on maternal sera during pregnancy. In 31
      children the infection was primary and 31 children had reactivated (recurrent or
      secondary) congenital CMV infection. Infection type could not be determined in 14
      children. Transient neonatal symptoms were apparent in 22 children and eight
      children had classical neurological CMV sequelae. Heterogeneous neurological
      disorders were found in 13 children. No significant differences in height,
      weight, and growth were found. The median follow-up time was 10 years. From 4
      years old children with congenital CMV infection were taller than the reference
      standard. At 1 and 2 years, those children with primary congenital CMV infection
      were borderline shorter than reference standard, and from 4 years children with
      reactivated CMV infection were taller than the reference standard. In conclusion,
      no evidence was found verifying that congenital CMV infection causes short
      stature.

PMID- 14714745
TI  - Intellectual development and thyroid function in children who were breast-fed by
      thyrotoxic mothers taking methimazole.
AB  - OBJECTIVE: Recent studies have shown normal thyroid function in infants whose
      mothers receive methimazole (MMI) during breast-feeding. This study evaluates the
      long-term effect of MMI on thyroid function and intellectual development of such
      children. DESIGN AND METHODS: Eighty-two children aged between 48 and 86 months
      were studied. Forty-two children had been breast-fed while their thyrotoxic
      lactating mothers received daily doses of MMI 20-30 mg in the first, 10 mg in the
      second and 5-10 mg for additional 10 months of therapy. Thyroid function of
      infants remained normal during the one year of MMI therapy of their mothers.
      Forty other infants served as controls. Serum T4, T3, and TSH concentrations,
      urinary iodine, thyroid antibodies, intelligence quotient (IQ), verbal and
      functional (performance) components (Wechsler and Goodenough tests) were measured
      in all children of the two groups. RESULTS: Height, weight, serum T4, T3, TSH and
      antithyroid antibody titers were not different between children in the two
      groups. The mean IQ was 107 +/- 17 vs 106 +/- 16 (Goodenough test) and 103 +/- 10
      vs 103 +/- 16 (Wechsler test) for children of thyrotoxic mothers and control
      children, respectively. There was no difference in verbal and functional IQ and
      their components between children of thyrotoxic MMI treated mothers and control
      children. CONCLUSION: Thyroid function and physical and intellectual development
      of breast-fed infants whose thyrotoxic lactating mothers were treated with 20-30
      mg doses of MMI daily are normal at age 48 to 86 months.

PMID- 14714746
TI  - Plasma homocysteine concentrations in adolescents with subclinical
      hypothyroidism.
AB  - OBJECTIVE: Hyperhomocysteinemia is a risk factor for premature atherosclerotic
      vascular disease and venous thrombosis. The aim of the present study was to
      assess plasma total homocysteine (tHCys) concentrations in adolescent patients
      with subclinical hypothyroidism. PATIENTS AND METHODS: Nineteen patients with
      subclinical hypothyroidism and 19 healthy children were studied. Fasting plasma
      concentrations of tHCys and its putative determinants (plasma concentrations of
      free thyroxine [FT4], folate, vitamin B12 and renal function) were measured.
      RESULTS: tHCys concentrations showed no statistical difference between patients
      and controls (p > 0.05). Moreover, the difference in tHCys and total cholesterol
      concentrations was not significant between patients with mild TSH elevations (<
      or = 10 mIU/l) and patients with prominent TSH elevations (> 10 mIU/l). No
      correlation was found between tHCys concentrations and its putative determinants.
      CONCLUSIONS: We concluded that plasma tHCys concentrations were not increased in
      adolescent patients with subclinical hypothyroidism.

PMID- 14714747
TI  - Pediatric Graves' disease: outcome and treatment.
AB  - Graves' disease treatment in children and adolescents includes antithyroid drugs
      (ATD), 131I (RI) or subtotal thyroidectomy (CX), all of which present beneficial
      effects and disadvantages. OBJECTIVE: To review our experience in the management
      of pediatric patients with Graves' disease considering the therapeutic strategies
      used. PATIENTS AND METHODS: Clinical and biochemical data of 116 children (23
      boys) aged 11.2 +/- 3.7 years at diagnosis were reviewed. Outcome and remission
      were evaluated and persistency at 10 years calculated with Kaplan Meier analysis.
      RESULTS: Initially 113/116 patients received ATD, two RI and one CX. After 10
      years of follow up, 38 remitted with ATD, 23 were persistently hyperthyroid with
      ATD, 38 received RI, one underwent CX, and 13 were lost to follow up. The
      cumulative proportion with persistent hyperthyroidism at 10 years was 31%.
      CONCLUSIONS: ATD, although the first choice of treatment, was long-lasting and
      achieved a low remission rate at 10 years of follow up. Conversely, RI was shown
      to be a safe, low cost, efficient and definitive alternative for Graves' disease
      treatment in children and adolescents.

PMID- 14714748
TI  - Rewarming index of the lower leg assessed by infrared thermography in adolescents
      with type 1 diabetes mellitus.
AB  - The aim of this study was to determine whether infrared thermography before and
      after challenge of the lower leg in cold water may be a useful tool to detect
      abnormalities in skin blood flow in adolescent asymptomatic patients with type 1
      diabetes mellitus (DM1) and to assess the optimal setting of skin temperature
      measurements. Twenty-five adolescents (10 female, 15 male, mean age 21.2 +/- 6.2
      years, body mass index [BMI] 23.0 +/- 2.1 kg/m2) with a duration of DMI of 13.8
      +/- 5.4 years and mean HbA1c levels 8.5 +/- 1.3% were compared to age- and sex
      matched controls (BMI 22.9 +/- 2.2 kg/m2). Seven defined sites of the lower leg
      were assessed by infrared thermography before and for 10 min after exposure of
      the leg to 14 degrees C cold water. As skin temperature before exposure to cold
      water differs from individual to individual and basal temperature was
      significantly warmer in patients at the tip of the first (p < 0.05) and fifth (p
      < 0.05) toe, the rewarming index was calculated in order to compare data.
      Rewarming indexes of skin temperature during the whole measurement procedure (0
      10 min) were significantly lower at the tip of the first (p < 0.05) and fifth (p
      < 0.01) toes and from minute 2-10 also at the inner ankle (p < 0.05) in patients
      compared to healthy controls. Rewarming indexes of the other four sites were not
      significantly different between patients and controls. Infrared thermography of
      the lower leg after cold water exposure is an easily applicable method and a
      useful tool to detect abnormalities of skin blood flow in adolescents with DM1
      especially at the tips of the first and fifth toes and the inner ankle.

PMID- 14714749
TI  - IA-2A positivity rate at manifestation of type 1 diabetes mellitus in Slovak
      children culminates in September.
AB  - BACKGROUND: New cases of type 1 diabetes mellitus (DM1) in Slovak children
      accumulate in late summer, autumn and winter. HYPOTHESES: Children manifesting
      the disease in these seasons have higher autoantibody positivity than those first
      diagnosed in spring or summer. PATIENTS AND METHODS: One hundred and fifty Slovak
      children (and adolescents), aged 1-14 (15-17) years at the manifestation of DM1,
      born 1978-2000, with the disease manifested 1989-2001, were investigated at
      diagnosis by IA-2A, GADA and IAA autoantibody positivity, using standard
      radioimmunoassay procedures. The resulting risk score values (0-1) were related
      to calendar days of diagnosis. Their annual, semi-annual and quarterly
      periodicity was tested using Halberg's cosinor regression. RESULTS: Only IA-2A
      positivity at the time of diagnosis showed significant seasonal cycling, with the
      acme around the autumn equinox and with the nadir in spring. There was no
      increase of this positivity in winter. CONCLUSION: The maximum autoantibody
      levels were found for those manifesting the disease in late summer and early
      autumn--the only time of year in Slovakia when both the numbers of births of
      future diabetic children as well as those of manifestation of new cases are
      significantly above average.

PMID- 14714750
TI  - Analysis of coding and promoter sequences of the IGF-I gene in children with
      growth disorders presenting with normal level of growth hormone.
AB  - The insulin-like growth factor-I (IGF-I) gene was analyzed in a population of
      children with growth disorders presenting normal GH and low IGF-I. We thus tried
      to detect any mutation in the IGF-I gene that could be responsible for short
      stature in children, using PCR, single-strand conformation polymorphism (SSCP)
      analysis, followed by DNA cloning and sequencing. We demonstrated in all examined
      children significant changes in the promoter region of the IGF-I gene (P1 IGF-I).
      Nucleotide sequence changes, such as CC-->GT and A-->G, and their localization
      are described. The results obtained excluded mutations in the coding sequence of
      the IGF-I gene. We conclude that testing the IGF-I P1 region, using PCR/SSCP
      analysis, could be useful in the diagnosis of growth disorders.

PMID- 14714752
TI  - Serum leptin levels and their relationship to tumor necrosis factor-alpha and
      interleukin-6 in neonatal sepsis.
AB  - Circulating leptin concentrations are raised in animal models of inflammation and
      sepsis and leptin production is also increased in rodents by administration of
      endotoxin or cytokines. The purpose of this study was to investigate the effect
      of sepsis on serum leptin concentration and whether circulating leptin was
      related to tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
      release in newborn infants. Plasma leptin, TNF-alpha and IL-6 were measured in 20
      neonates with culture-proven sepsis as soon as sepsis was diagnosed and after
      recovery and in 15 healthy control infants. There was no significant difference
      in plasma leptin levels between septic and control infants (p > 0.05); there was
      also no difference in plasma leptin levels in septic neonates before and after
      therapy (p > 0.05). No relationship between leptin and TNF-alpha (r = 0.16, p >
      0.05) or IL-6 (r = 0.12, p > 0.05) was identified. These findings suggest that a
      major role of leptin in acute neonatal sepsis appears unlikely.

PMID- 14714751
TI  - Partial glucocorticoid resistance in obese children detected by very low dose
      dexamethasone suppression test.
AB  - The effects of glucocorticoids (GC) are mediated by the activation of specific
      receptors that can be quantified in vitro by several laboratory tests. In vivo,
      other tests to determine GC sensitivity have been described, but only employing
      pharmacological doses. In this study, we used a very low dose of dexamethasone,
      an in vivo model to assess individual GC sensitivity. Fifty-five obese children
      and adolescents and 17 controls were studied. The patients were submitted to four
      12-h urine collections, starting at 22:00 h; dexamethasone was administered
      orally at the end of the second urine sample. Patients were divided in the
      following groups: group Ob75 (n = 29) and the control group (n = 17) received
      dexamethasone 75 microg/m2, and group Ob150 (n = 26) received dexamethasone 150
      microg/m2. Urinary cortisol was determined by RIA and expressed as microg/m2/12
      h. All patients and controls showed a circadian rhythm before GC, which was
      maintained after dexamethasone only in controls. In the obese patients the
      circadian rhythm was abolished following both doses of dexamethasone, but more
      prominently with the dose of 150 microg/m2. In the obese group given 75
      microg/m2, urinary cortisol inhibition was only observed in the first 12 h after
      dexamethasone, suggesting a partial and shorter suppression of the hypothalamic
      pituitary axis. In both control and obese patients, the very low dose of
      dexamethasone was able to create a gradient of cortisol suppression that could be
      useful to identify an individual's sensitivity to glucocorticoids.

PMID- 14714753
TI  - Serum levels of bile salt-stimulated lipase and breast feeding.
AB  - OBJECTIVES: Bile salt-stimulated lipase (BSSL) is present in the sera of healthy
      humans, may affect lipoprotein structure and composition, and reduce
      atherogenicity of oxidized LDL-cholesterol. Our aims were to examine serum levels
      of BSSL in breast- and formula-fed infants, and explore the influence of BSSL on
      serum lipid profile and oxidative status. METHODS: Infants (2-8 weeks old) were
      prospectively enrolled. Blood was drawn for serum levels of BSSL, total
      antioxidant status (TAS), and lipid profile. RESULTS: Serum levels of BSSL were
      similar in breast-fed (0.28 +/- 0.15 microg/l, n = 18) and formula-fed (0.31 +/-
      0.09 microg/l, n = 15) infants, and were much lower than reported levels for
      adults. In breast-fed infants only, BSSL levels were correlated with LDL
      cholesterol serum levels (r = -0.53, p = 0.04). Total cholesterol (119.2 +/- 34.3
      mg/dl vs 97 +/- 27.2, and p = 0.05) and LDL-cholesterol serum levels (50.5 +/-
      26.1 mg/dl vs 33.3 +/- 20.3, p = 0.05), were elevated in breast-fed compared with
      formula-fed infants, but TAS was similar in both groups (1.02 +/- 0.18 mmol/l and
      0.98 +/- 0.12 mmol/l, respectively). CONCLUSIONS: Lack of difference in BSSL
      serum levels between formula- and breast-feeding, and lower BSSL levels in
      infants compared to adults, suggest that human milk does not contribute to BSSL
      serum levels.

PMID- 14714754
TI  - Borjeson-Forssman-Lehmann syndrome and multiple pituitary hormone deficiency.
AB  - We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T
      (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple
      pituitary hormone deficiency. Biochemical investigations and radiology confirmed
      growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic
      hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have
      optic nerve hypoplasia. This family suggests that the BFL gene product may play
      an important role in midline neuro-development including the hypothalamo
      pituitary axis.

PMID- 14714755
TI  - Pituitary apoplexy due to prolactinoma in a Taiwanese boy: patient report and
      review of the literature.
AB  - We report a Taiwanese boy who presented with apoplexy of a prolactinoma. A 12
      9/12 year-old boy presented to our clinic with headache and visual deficit of
      bitemporal hemianopsia. Skull X-ray showed an enlarged sella. Magnetic resonance
      imaging (MRI) of the sella turcica showed a 4 x 2.5 x 2.5 cm mass, located at the
      sella turcica and extending upward to compress the optic chiasm. Preoperative
      laboratory data showed hyperprolactinemia, hypothyroidism and hypocortisonism.
      After a stress dose of i.v. hydrocortisone was given, he underwent transsphenoid
      surgery to remove the tumor. Immunohistochemical stains were positive for PRL in
      the tumor cells. After surgery, he suffered from neurogenic diabetes insipidus,
      hypopituitarism and hyperprolactinemia, with serum PRL level of 491 ng/ml. Visual
      field examination was normal 4 months later. In conclusion, pituitary apoplexy is
      rare in children but should be considered if a patient suffers from headache,
      vomiting, and visual deficit. Brain MRI is preferred for diagnosis. Dopaminergic
      agonists should be given if residual tumor or recurrence of prolactinoma is found
      after transsphenoidal surgery.

PMID- 14714756
TI  - Trimethoprim-sulfamethoxazole induced prolonged hypoglycemia in an infant with
      MHC class II deficiency: diazoxide as a treatment option.
AB  - Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP
      SMX) has generally been reported in adults who had renal impairment or in
      patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with
      immunodeficiency due to major histocompatibility complex class II expression
      defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX
      administration. High insulin and C-peptide levels were documented at the time of
      hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was
      administered which resolved hypoglycemia in 2 months.

PMID- 14714757
TI  - Adrenocortical adenoma associated with inadequately treated congenital adrenal
      hyperplasia.
AB  - We report a 6 year-old boy with the simple virilizing form of 21-hydroxylase
      deficiency in whom an adrenal adenoma developed following 5 years of steroid
      treatment. Extremely high levels of basal serum 17alpha-hydroxyprogesterone as
      well as an exaggerated response of 17alpha-hydroxyprogesterone to
      adrenocorticotropic hormone confirmed congenital adrenal hyperplasia at 7 years
      of age. Initially elevated serum steroid levels were restrained by high dose
      hydrocortisone therapy, but he chronically tended to take inadequate doses of
      glucocorticoid. At 12 years of age an adenoma was found in the cortex of the
      hyperplastic right adrenal gland. The importance of early diagnosis and
      compliance with medication in the simple virilizing form of 21-hydroxylase
      deficiency is stressed.

PMID- 14714758
TI  - Synthesis and conformational analysis of a locked analogue of carbovir built on a
      bicyclo[3.1.0]hex-2-enyl template.
AB  - The synthesis and biological evaluation of a carbovir analogue (5) built on a
      bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using
      density functional theory at the B3LYP/6-31G* level has been carried out on the
      rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the
      bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13)
      containing exo- and endo-fused cyclopropane rings. The results show that while
      the planar configuration of the fused cyclopentane ring of compound 5 helps
      retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir
      to easily adopt a planar or puckered conformation with little energy penalty may
      prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13
      that were inactive against HIV exhibited stiffer resistance to having a planar,
      fused cyclopentane moiety.

PMID- 14714759
TI  - Studies towards the large scale chemical synthesis of the precursors of
      ribonucleosides-3',4',5',5''-2H4 and -2',3',4',5',5''-2H5.
AB  - A summary delineating the large scale synthetic studies to prepare labeled
      precursors of ribonucleosides-3',4',5',5''-2H4 and -2',3',4',5',5''-2H5 from D
      glucose is presented. The recycling of deuterium-labeled by-products has been
      devised to give a high overall yield of the intermediates and an expedient
      protocol has been elaborated for the conversion of 3-O-benzyl-alpha,beta-D
      allofuranose-3,4-d2 6 to 1-O-methyl-3-O-benzyl-2-O-t-butyldimethylsilyl
      alpha,beta-D-ribofuranose-3,4,5,5'-d4 16 (precursor of ribonucleosides
      3',4',5',5''-2H4) or to 1-O-methyl-3,5-di-O-benzyl-alpha,beta-D-ribofuranose
      3,4,5,5'-d4 18 (precursor of ribonucleosides-3',4',5',5''-2H4).

PMID- 14714760
TI  - Efficacy of methylenecyclopropane analogs of nucleosides against herpesvirus
      replication in vitro.
AB  - We have reported previously that purine methylenecyclopropane analogs are potent
      agents against cytomegaloviruses. In an attempt to extend the activity of these
      compounds, the 2-amino-6-cyclopropylaminopurine analog, QYL-1064, was selected
      for further study by modifying the purine 6 substituent. A total of 22 analogs
      were tested against herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella
      zoster virus (VZV), human cytomegalovirus (HCMV), murine cytomegalovirus (MCMV),
      Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV-6) and human herpesvirus
      type 8 (HHV-8). Ten of the analogs had activity against at least one of the
      viruses tested. One compound had moderate activity against HSV-1 and six had
      activity against VZV. All but one compound was active against HCMV with a mean
      EC50 of 2.1 +/- 0.6 microM, compared with a mean EC50 of 3.9 +/- 0.8 microM for
      ganciclovir. Of special interest was the fact that eight of the ten compounds
      were active against both HHV-6A and HHV-6B with mean EC50 values of 6.0 +/- 5.2
      mciroM and <2.4 +/- 1.5 microM, respectively. Only two compounds had activity
      against EBV, whereas all but one compound was active against HHV-8 with a mean
      EC50 of 3.1 +/- 1.7 microM. These results indicate that members of this series of
      methylenecyclopropane analogs are highly active against HCMV, HHV-6, and HHV-8
      but are less active against HSV, VZV, and EBV.

PMID- 14714761
TI  - Cyclosaligenyl pronucleotides of 5-iodo and 5-trifluoromethyl-1-(2-deoxy-beta-D
      ribofuranosyl)-2,4-difluorobenzene mimics of thymidine: synthesis and evaluation
      of this pronucleotide monophosphate delivery system for compounds with potential
      anticancer activity.
AB  - A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes
      possessing a 5-I or 5-CF3 substituent, that were originally designed as thymidine
      mimics, were coupled via their 5'-OH group to a cyclosaligenyl (cycloSal) ring
      system having a variety of C-3 substituents (Me, OMe, H). The 5'-O-cycloSal
      pronucleotide concept was designed to effect a thymidine kinase-bypass, thereby
      providing a method for the intracellular delivery and generation of the 5'-O
      monophosphate for nucleosides that are poorly phosphorylated. The 5'-O-cycloSal
      pronucleotide phosphotriesters synthesized in this study were obtained as a 1:1
      mixture of two diastereomers that differ in configuration (S(P) or R(P)) at the
      asymmetric phosphorous center. The (S(P))- and (R(P))-diastereomers for the 5'-O
      3-methylcycloSal- and 5'-O-3-methoxycycloSal derivatives of 1-(2-deoxy-beta-D
      ribofuranosyl)-2,4-difluoro-5-iodobenzene were separated by silica gel flash
      column chromatography. This class of cycloSal pronucleotide compounds generally
      exhibited weak cytotoxic activities in a MTT assay (CC50 values in the 10(-3) to
      10(-4) M range), against a number of cancer cell lines (143B, 143B-LTK, EMT-6,
      Hela, 293), except for cyclosaligenyl-5'-O-[1'-(2,4-difluoro-5-iodophenyl)-2'
      deoxy-beta-D-ribofuranosyl]phosphate that was more potent (CC50 values in the 10(
      5) to 10(-6) M range), than the reference drug 5-iodo-2'-deoxyuridine (IUDR)
      which showed CC50 values in the 10(-3) to 10(-5) M range.

PMID- 14714762
TI  - Design and synthesis of a series of chlorinated 3-deazaadenine analogues.
AB  - A series of chlorinated adenine analogues were designed with sights set on the
      development of potential antitumor agents. During the synthetic efforts, two
      unexpected compounds were identified. Their synthesis, along with synthesis of
      the chlorinated targets is presented herein.

PMID- 14714763
TI  - Synthesis of base substituted 2-hydroxy-3-(purin-9-yl)-propanoic acids and 4
      (purin-9-yl)-3-butenoic acids.
AB  - Alkylation of 6-chloropurine and 2-amino-6-chloropurine with bromoacetaldehyde
      diethyl acetal afforded 6-chloro-9-(2,2-diethoxyethyl)purine (3a) and its 2-amino
      congener (3b). Treatment of compounds 3 with primary and secondary amines gave
      the N6-substituted adenines (5a-5c) and 2,6-diaminopurines (5d-5f). Hydrolysis of
      3 resulted in hypoxanthine (6a) and guanine (6b) derivatives, while their
      reaction with thiourea led to 6-sulfanylpurine (7a) and 2-amino-6-sulfanylpurine
      (7b) compounds. Treatment with diluted acid followed by potassium cyanide
      treatment and acid hydrolysis afforded 6-substituted 3-(purin-9-yl)- and 3-(2
      aminopurin-9-yl)-2-hydroxypropanoic acids (8-10). Reaction of compounds 3 with
      malonic acid in aqueous solution gave exclusively the product of isomerisation, 6
      substituted 4-(purin-9-yl)-3-butenoic acids (15).

PMID- 14714764
TI  - Synthesis and anti-cancer activity of some novel 5-azacytosine nucleosides.
AB  - 1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy
      1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine
      to obtain alpha and beta anomers of nucleosides. All four nucleosides were
      reduced to the corresponding dihydro derivatives and deblocked to give target
      compounds. All eight target compounds were evaluated in a series of human cancer
      cell lines in culture. Only 2'-deoxy-4'-thio-5-azacytidine (3beta) was found to
      be cytotoxic in all the cell lines and was further evaluated in vivo. Details of
      the synthesis and biological activity are reported.

PMID- 14714765
TI  - Synthesis and antiviral activity of 2-substituted analogs of triciribine.
AB  - Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and
      antineoplastic activity at low or submicromolar concentrations. In an effort to
      improve and better understand this activity, we have conducted a structure
      activity relationship study to explore the effect of substitutions at the 2
      position of triciribine. 2-Methyl- (2-Me-TCN), 2-ethyl- (2-Et-TCN), 2-phenyl- (2
      Ph-TCN), 2-chloro- (2-Cl-TCN), and 2-aminotriciribine (2-NH2-TCN) were designed
      and synthesized to determine the effects of substitutions at the 2-position which
      change the steric, electronic, and hydrophobic properties of TCN, while
      maintaining the integrity of the tricyclic ring system. These compounds were
      evaluated for activity against human immunodeficiency virus (HIV-1), herpes
      simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV) and were found to
      be either less active than TCN and TCN-P or inactive at the highest
      concentrations tested, 100 microM. We conclude that substitutions at the 2
      position of triciribine adversely affect the antiviral activity most likely
      because these analogs are not phosphorylated to active metabolites.

PMID- 14714766
TI  - Synthesis and studies of 3'-C-trifluoromethyl-beta-D-ribonucleosides bearing the
      five naturally occurring nucleic acid bases.
AB  - 3'-C-Trifloromethyl-beta-D-ribonucleoside derivatives bearing the five naturally
      occurring nucleic acid bases have been synthesized. All these derivatives were
      prepared by glycosylation reactions of purine and pyrimidine bases with a
      suitable peracylated 3-C-trifluoromethyl ribofuranose precursor. After
      deprotection, the resulting title nucleoside analogues were tested for their
      inhibitory properties against the replication of HIV, HBV and several RNA
      viruses. However, none of these compounds showed significant antiviral activity.

PMID- 14714767
TI  - Carotid Doppler microembolic signals in patients one year after heart valve
      surgery.
AB  - Doppler ultrasound has been used to detect microemboli during and after
      cardiopulmonary bypass (CPB). The aim of the present study was to examine the
      frequency of microembolic signals (MES) in patients one year after heart valve
      replacement, to look for possible risk factors associated with MES and for any
      correlation with cerebral events. One hundred patients, 69 male and 31 female,
      mean age 66.3 +/- 12.4 years, were examined one year after heart valve
      replacement. Thirty patients, 61% male and 39% female, mean age 62.5 +/- 8.7
      years, who had undergone cardiovascular operations without heart valve pathology
      served as controls. A newly developed microemboli detector, EMEX-25 (Hatteland
      Instrumentering, Norway) was used to detect MES from both carotid arteries. MES
      were detected in 61% of the valve patients. A correlation was found between the
      number of MES, previous cardiovascular operations, emergency surgery and
      EuroSCORE (p <0.05). There was no correlation between the number of MES and the
      level of anticoagulation expressed as international normalization ratio (INR),
      atrial fibrillation, serum-cholesterol, New York heart association (NYHA) class,
      gender, age, valve type or valve position. The average number of MES was not
      increased in seven patients who had experienced major (three) or minor
      (transient, four) cerebral events during follow-up. In the 30 nonvalve controls,
      MES were detected in 46% of the patients. MES were detected in valve patients as
      well as in nonvalve patients one year after surgery. In valve patients, a
      significant correlation was found between MES and previous surgery, emergency
      surgery and EuroSCORE. There was no correlation between the number of MES and INR
      level or postoperative cerebral events.

PMID- 14714768
TI  - Measurement of systemic carbon dioxide production during cardiopulmonary bypass:
      a comparison of Fick's principle with oxygentor exhaust output.
AB  - Theoretically, systemic carbon dioxide (VCO2) production should be an alternative
      means to systemic oxygen uptake (VO2) for estimating the global efficacy of
      cardiopulmonary bypass (CPB). This study compared two methods of estimating VCO2:
      Fick's principle and oxygenator exhaust carbon dioxide (CO2) output. Both of
      these estimates were then compared with VO2. Fifty-one patients (39 male and 12
      female) undergoing elective cardiac surgery requiring CPB were studied. Blood
      sampling was performed and measurements recorded during active cooling,
      environmental cooling/stable hypothermia and during rewarming. Blood samples were
      measured for CO2 tension from which content was estimated. VCO2 was calculated as
      the product of the arteriovenous difference in CO2 content and pump flow rate
      (Fick's principle), or the fresh gas flow rate and concentration of the
      oxygenator exhaust CO2 (output technique). Over all measurements, method
      comparison analysis revealed a large mean bias of 41 (95% confidence intervals
      (CI) 32-50) mL/min with very wide limits of agreement (-23, 105 mL/min).
      Regression analysis found that the bias was also proportional to the size of
      measurement (beta = 0.75 (95% CI 0.55, 0.95)). Although both methods of VCO2
      correlated significantly with VO2 (p < 0.01), regression analysis found that the
      coefficients (beta) of both techniques had wide CI (Fick's principle: beta = 1.37
      (95% CI 1.20, 1.54); output technique: beta = 0.58 (95%CI 0.44, 0.71)). In
      conclusion, both techniques of VCO2 cannot be used interchangeably, and both are
      imprecisely related to VO2 as estimated by Fick's principle.

PMID- 14714769
TI  - Effects of N-acetylcysteine on pulmonary function in patients undergoing coronary
      artery bypass surgery with cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) has been implicated in causing poor pulmonary gas
      exchange postoperatively in patients undergoing coronary artery bypass grafting
      (CABG) procedures. In this prospective, randomized, double-blind, placebo
      controlled study, we examined the pulmonary effects of N-acetylcysteine (NAC) in
      patients undergoing CABG. Twenty patients undergoing elective CABG and early
      tracheal extubation were randomized into two groups. Group I (ten patients)
      received a physiologic salt solution as a placebo in a continuous intravenous
      infusion for one hour before CPB and 24 hours after CPB; Group II (ten patients)
      received 100 mg/ kg NAC intravenously for one hour before CPB and 40 mg/kg/day at
      24 hours after CPB. Perioperative hemodynamic and pulmonary data were recorded.
      Postoperative tracheal extubation was accomplished at the earliest appropriate
      time. The postoperative clinical course was similar in the two groups. Both
      groups exhibited significant postoperative increases in A-a oxygen gradient (p <
      0.01), but patients in Group II exhibited significantly lower increases in
      postoperative A-a oxygen gradient (p < 0.006). Other hemodynamic and pulmonary
      data (pulmonary capillary wedge pressure, pulmonary vascular resistance (PVR),
      cardiac index (CI), shunt flow, dynamic lung compliance and static lung
      compliance) exhibited no differences between the groups. There was no significant
      difference in terms of intubation time. The malondialdehyde (MDA) increase in
      Group II following CPB was found to be significantly lower than in Group I (p =
      0.043). This clinical study reveals that administration of NAC to patients
      undergoing elective CABG with CPB improves systemic oxygenation. There was no
      effect in other pulmonary parameters and in terms of intubation time.

PMID- 14714770
TI  - Importance of internal mammary artery perfusion in cardiac ischemia and
      reperfusion.
AB  - PURPOSE: Our purpose was to investigate the changes in antioxidant defense
      systems due to internal mammary artery (IMA) perfusion during coronary artery
      bypass graft (CABG) operations in which proximal anastomoses were completed under
      partial bypass with the aid of a side-biting clamp. MATERIAL AND METHOD: Twenty
      five patients to be studied were divided into two groups according to the
      criterion of whether during proximal anastomoses left internal mammary artery
      (LIMA) perfusion was applied (n = 15, LIMA group) or not (n = 10, non-LIMA
      group). The erythrocyte catalase (CAT), superoxide dismutase (SOD), serum lipid
      peroxidation (LPO) products and whole blood reduced glutathione (GSH) levels were
      measured in the blood samples taken from the coronary sinus before
      cardiopulmonary bypass (CPB) (t1), before declamping (t2), at the 5th min after
      declamping (t3), at the 5th (t4) and 15th (t5) min after removing the side-biting
      clamp. RESULTS: While erythrocyte CAT enzyme activity decreases in both groups
      after the basal measurements, no significant difference was detected between the
      groups. Although the GSH levels did not differ at t1, t2 and t3, they were found
      to be higher in the LIMA group at t4 (p = 0.006) and t5 (p = 0.021). The
      erythrocyte SOD enzyme activity decreased after the basal measurements in both
      groups, but this reduction was less in the LIMA group at t4 (p = 0.034) and t5 (p
      = 0.018) compared to the other group. LPO products rose in both groups when
      reperfusion started after declamping. The levels of LPO products were
      significantly higher at t4 and t5 in the non-LIMA group than the other group (p =
      0.011 and p = 0.008). CONCLUSION: If proximal anastomoses of coronary grafts are
      completed under partial bypass, permitting LIMA perfusion during this procedure
      will be beneficial to antioxidant defense systems.

PMID- 14714771
TI  - Increasing the antioxidative capacity of neonatal cardiopulmonary bypass prime
      solution: an in vitro study.
AB  - Inflammation and oxidative damage are believed to play an important role in the
      postoperative complications after cardiopulmonary bypass (CPB) in neonates.
      During the preparation of the prime, red blood cells (RBCs) release non-protein
      bound iron (NPBI) and free haemoglobin/haem (Hb/haem). The presence of these
      prooxidants in the prime solution may increase oxidative stress in neonates
      undergoing CPB. The solution used as the basis of the prime solution may
      influence the degree of this oxidative stress. We investigated the NPBI and the
      Hb/haem binding capacities of two different prime solutions: a prime based on
      pasteurized human albumin and a prime based on fresh frozen plasma. The presence
      of NPBI and free Hb/haem were measured during and after the preparation of the
      prime solution. Only in the albumin prime was NPBI detectable. However, in both
      primes, the concentrations of free Hb/haem increased. Thus, to reduce the
      prooxidative effects of NPBI and free Hb/haem, RBCs should be added to the prime
      at the last possible moment. Adding fresh frozen plasma should be considered, as
      this would result in no detectable NPBI in the prime solution.

PMID- 14714772
TI  - Bone wax cast to repair a cannula leakage during prolonged extracorporeal
      membrane oxygenation.
AB  - During prolonged extracorporeal perfusion, thin-walled wire-wound cannulas have
      become the standard for low resistance cannula access for extrathoracic
      cannulation. We present an unusual technique of bone wax casting to repair a leak
      in a cannula to continue long-term extracorporeal membrane oxygenation.

PMID- 14714773
TI  - Pericardial patch closure of an atrial septal defect using endoscopic robotic
      technology.
AB  - Significant progress has been made over the last several years in the area of
      minimally invasive cardiac surgery with beneficial clinical results and increased
      patient satisfaction. With the addition of robotic technology to the cardiac
      operating room come improvements in technical manual dexterity and decreased
      surgical trauma. This paper reports an endoscopic pericardial patch closure of an
      ostium secundum atrial septal defect (ASD) using a combination of the daVinci
      Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) and the PORT ACCESS
      System (CardioVations, Sommerville, NJ, USA) for full cardiopulmonary bypass
      (CPB). CPB, aortic occlusion, and cardioplegia delivery were accomplished via
      peripheral cannulation with the PORT ACCESS System. Two robotic arms, one
      endoscopic camera, and one working incision were placed through ports in the
      thorax. The ASD was closed with a gluteraldehyde fixed pericardial patch using
      both running and interrupted suture. CPB and aortic occlusion times were 160 and
      93 min, respectively. The patient was discharged on the second postoperative day
      and returned to normal lifestyle shortly thereafter. The benefits of peripheral
      access CPB and robotic technology to patients who do not want a median sternotomy
      provide an alternative method to traditional surgical intervention.

PMID- 14714774
TI  - When the blood-back detection system fails: an IABP case report.
AB  - A 74-year-old male patient's circulation was supported by an intra-aortic balloon
      for a period of six days following multiple cardiac infarcts. On the sixth day,
      several 'leak in IAB circuit' alarms appeared. The nursing staff checked the
      tubing and refilled the balloon, as described in the manual, without notifying
      the medical staff or perfusionist. A few hours later, the balloon showed a leak,
      as blood was seen in the catheter tubing. This leak resulted in considerable
      damage to the device caused by a large amount of blood migrating back to the
      tubing and flooding the internal drive system, due to a failing 'blood detection'
      sensor. The balloon catheter was removed percutaneously and intra-aortic
      counterpulsation was discontinued. The patient died 20 days later of heart
      failure. This raises doubts over the adequacy of the protective sensors of such
      devices and, importantly, how to interpret the present user manuals and the
      instructions for troubleshooting.

PMID- 14714775
TI  - A case report of mitral valve replacement in a patient with lupus antibody
      syndrome.
AB  - Systemic lupus erythematosis (SLE) is an autoimmune disease frequently
      accompanied by the presence of an antiphospholipid antibody (APA). Early referred
      to as the lupus anticoagulant (LAC), this APA consists of immunoglobulins that
      are known to interfere with coagulation tests that are phospholipid dependent.
      Such tests include the partial thromboplastin time (PTT), the activated clotting
      time (ACT) and may affect the thrombin time (TT). This challenges the cardiac
      surgical team and the perfusionist responsible for monitoring anticoagulation
      while performing cardiopulmonary bypass (CPB). A 46-year-old female with a
      history of SLE, severe mitral insufficiency, an anterior wall myocardial
      infarction, and the presence of a LAC was admitted for mitral valve surgery.
      Replacement of the mitral valve was accomplished successfully, utilizing CPB.
      Anticoagulation was managed using the Hepcon HMS PLUS, a device that calculates
      an individual's heparin dose response and permits assessment of the heparin
      concentration throughout the procedure. The patient recovered and was sent home
      16 days after surgery.

PMID- 14714776
TI  - Safe minimization of cardiopulmonary bypass circuit volume for complex cardiac
      surgery in a 3.7 kg neonate.
AB  - Over recent years, increasing awareness has been aroused to the hazards of the
      utilization of donor blood products. Particularly in neonate cardiac surgery
      employing cardiopulmonary bypass (CPB), the relative high priming volume of the
      CPB system and its adjunctive components, such as hemofilters, causes severe
      hemodilution and, therefore, particularly during extended perfusions, customarily
      requires priming of the system with autologous blood components. We report on our
      efforts to minimize the CPB system and adjust the perfusion strategy to the goal
      of transfusion-free CPB in a 3.7 kg neonate scheduled for repair of transposition
      of the great arteries.

PMID- 14714777
TI  - Management of potential gas embolus during closure of an atrial septal defect in
      a three-year-old.
AB  - Gas embolism occurring in adult patients supported with cardiopulmonary bypass is
      usually associated with mechanical complications. Management of gas embolism is
      less often described for the pediatric or neonatal patient. Measures to
      counteract gas embolism must be undertaken immediately if a satisfactory outcome
      is to be achieved. Here, the management of a three-year-old female patient, who
      was undergoing repair of a secundum atrial septal defect when the aortic cannula
      became dislodged and air entered the aorta, is described. Immediate
      implementation of an air embolism protocol, including (among other maneuvers)
      removal of air from the circuit, retrograde cerebral perfusion via the superior
      vena cava, and induction of cerebral hypothermia, may have aided in an acceptable
      outcome.

PMID- 14714778
TI  - The Schultz curve 25 years later: a research perspective.
AB  - The contemporary technical rationale for assessing effects ("impacts") of
      transportation noise on communities rests in large part on a purely descriptive
      dosage-effect relationship of the sort first synthesized by Schultz [J. Acoust.
      Soc. Am. 64, 377-405 (1978)]. Although U.S. federal adoption of an annoyance
      based rationale for regulatory policy has made this approach a familiar one, it
      is only one of several historical perspectives, and not necessarily the most
      useful for all purposes. Last reviewed by the U.S. Federal Interagency Committee
      on Noise (FICON) 10 years ago, the accuracy and precision of estimates of the
      prevalence of a consequential degree of noise-induced annoyance yielded by
      functions of noise exposure leave much to be desired. This tutorial article
      traces the development of the dosage-effect relationship on which FICON currently
      relies, in a wider historical context of efforts to understand and predict
      community response to transportation noise. It also identifies areas in which
      advances in genuine understanding might lead to improved means for predicting
      community response to transportation noise.

PMID- 14714779
TI  - On derivation of differential equations of coupled-mode propagation from the
      reciprocity principle.

PMID- 14714780
TI  - On the application of the reciprocity principle to coupled-mode propagation.

PMID- 14714782
TI  - Are conical segments useful for vocal-tract simulation?

PMID- 14714781
TI  - Relative importance of temporal envelope and fine structure in lexical-tone
      perception.

PMID- 14714783
TI  - Bridging automatic speech recognition and psycholinguistics: extending Shortlist
      to an end-to-end model of human speech recognition.

PMID- 14714784
TI  - Preceding phonetic context affects perception of nonspeech.

PMID- 14714785
TI  - Characterization of chaotic dynamics in the vocalization of Cervus elaphus
      corsicanus.

PMID- 14714786
TI  - Sound focusing in rooms. II. The spatio-temporal inverse filter.
AB  - The potential of time reversal processing for room acoustics has been extensively
      investigated in the companion of this paper [J. Acoust. Soc. Am. 113(3), 1533
      1543 (2003)]. In particular, a simple implementation of a loudspeaker time
      reversal antenna able to take advantage of the multiple reflections in
      reverberating rooms demonstrates its potential for audible range acoustics while
      improving focusing both in space and time. However, loss of information (e.g.,
      sound absorption in walls or nonequalized bandwidths of the loudspeakers) during
      a time reversal experiment degrades the quality of time reversal focusing. In
      this paper, a more sophisticated technique called spatio-temporal inverse
      filtering is investigated that achieves time and space deconvolution of the
      propagation operator between the loudspeakers antenna and a set of microphones
      embedded inside the insonified volume. Theoretical and experimental comparisons
      between time reversal and inverse filter focusing are presented. Finally,
      advantages and limitations of both focusing approaches are highlighted.

PMID- 14714787
TI  - Transient fluid-structure interaction of elongated bodies by finite-element
      method using elliptical and spheroidal absorbing boundaries.
AB  - In a domain method of solution of exterior scalar wave equation, the radiation
      condition needs to be imposed on a truncation boundary of the modeling domain.
      The Bayliss, Gunzberger, and Turkel (BGT) boundary dampers, which require a
      circular cylindrical and spherical truncation boundaries in two-(2D) and three
      (3D)-dimensional problems, respectively, have been particularly successful in the
      analysis of scattering and radiation problems. However, for an elongated body,
      elliptical (2D) or spheroidal (3D) truncation boundaries have potential to reduce
      the size of modeling domain and hence computational effort. For harmonic
      problems, such extensions of the first- and second-order BGT dampers are
      available in the literature. In this paper, BGT dampers in both elliptical and
      spheroidal coordinate systems have been developed for transient problems
      involving acoustic radiation as well as fluid-structure interaction and
      implemented in the context of finite-element method based upon unsymmetric
      pressure-displacement formulation. Applications to elongated radiators and shells
      are reported using several numerical examples with excellent comparisons. It is
      demonstrated that significant computational economy can be achieved for elongated
      bodies with the use of these dampers.

PMID- 14714788
TI  - Acoustic field of a wedge-shaped section of a spherical cap transducer.
AB  - The acoustic pressure field at an arbitrary point in space is derived for a wedge
      shaped section of a spherical cap transducer using the spatial impulse response
      (SIR) method. For a spherical surface centered at the origin, a wedge shape is
      created by taking cuts in the X-Y and X-Z planes and removing the smallest
      surface component. Analytic expressions are derived for the SIR based on spatial
      location. The expressions utilize the SIR solutions for a spherical cap
      transducer [Arditi et al., Ultrason. Imaging 3, 37-61 (1981)] with additional
      terms added to account for the reduced surface area of the wedge. Results from
      the numerical model are compared to experimental measurements from a wedge
      transducer with an 8-cm outer diameter and 9-cm geometric focus. The experimental
      and theoretical -3-dB beamwidths agreed to within 10% +/- 5%. The SIR model for a
      wedge-shaped transducer is easily extended to other spherically curved transducer
      geometries that consist of combinations of wedge sections and spherical caps.

PMID- 14714789
TI  - The acoustic impedance of a circular orifice in grazing mean flow: comparison
      with theory.
AB  - It is well known that the presence of a grazing mean flow affects the acoustic
      impedance of an aperture, but the detailed nature and understanding of the
      influence is still unknown. In this paper, results from a recent theoretical
      analysis of the problem are compared with a new set of experimental results. The
      purpose is twofold. First, the experimental results are used to validate the
      theory. It is found that the theory predicts the resistance quite well, but not
      the reactance. Second, the theory is used to try and give some physical
      understanding to the experimental results. In particular, some scaling laws are
      confirmed, and it is also shown that measured negative resistance values are to
      be expected. They are not erroneous, as previously thought. Former sets of
      experimental data for this problem are notable for the amount of variation that
      they display. Thus, both the theory and the new experimental results are also
      compared with those earlier detailed results that most closely conform to the
      conditions assumed here, namely fully developed turbulent pipe flow of low Mach
      number past circular orifices. The main field of application is in flow ducts, in
      particular, flow through perforated tubes in exhaust mufflers.

PMID- 14714790
TI  - Measurement of elastic nonlinearity of soft solid with transient elastography.
AB  - Transient elastography is a powerful tool to measure the speed of low-frequency
      shear waves in soft tissues and thus to determine the second-order elastic
      modulus mu (or the Young's modulus E). In this paper, it is shown how transient
      elastography can also achieve the measurement of the nonlinear third-order
      elastic moduli of an Agar-gelatin-based phantom. This method requires speed
      measurements of polarized elastic waves measured in a statically stressed
      isotropic medium. A static uniaxial stress induces a hexagonal anisotropy
      (transverse isotropy) in solids. In the special case of uniaxially stressed
      isotropic media, the anisotropy is not caused by linear elastic coefficients but
      by the third-order nonlinear elastic constants, and the medium recovers its
      isotropic properties as soon as the uniaxial stress disappears. It has already
      been shown how transient elastography can measure the elastic (second-order)
      moduli in a media with transverse isotropy such as muscles. Consequently this
      method, based on the measurement of the speed variations of a low-frequency (50
      Hz) polarized shear strain waves as a function of the applied stress, allows one
      to measure the Landau moduli A, B, C that completely describe the third-order
      nonlinearity. The several orders of magnitude found among these three constants
      can be justified from the theoretical expression of the internal energy.

PMID- 14714791
TI  - Thermal effects on acoustic streaming in standing waves.
AB  - Acoustic streaming generated by standing waves in channels of arbitrary width is
      investigated analytically. In a previous paper by the authors [J. Acoust. Soc.
      Am. 113, 153-160 (2003)], a purely viscous fluid in a two-dimensional channel was
      considered. That analysis is extended here to a gas in which heat conduction and
      dependence of the viscosity on temperature are taken into account. Calculations
      are presented for typical working gases used in thermoacoustic engines at
      standard temperature and pressure. In channels that are very wide in comparison
      with the viscous penetration depth, which is the Rayleigh streaming regime, the
      influence of the two thermal effects is comparable but small. The same is true in
      very narrow channels, having widths on the order of the viscous penetration
      depth. In channels having intermediate widths, 10-20 times the viscous
      penetration depth, the effect of heat conduction can be substantial. The analysis
      is performed for cylindrical tubes as well as two-dimensional channels, and the
      results are found to be qualitatively the same.

PMID- 14714792
TI  - Excess attenuation of an acoustic beam by turbulence.
AB  - A theory based on the concept of a spatial sinusoidal diffraction grating is
      presented for the estimation of the excess attenuation in an acoustic beam. The
      equation of the excess attenuation coefficient shows that the excess attenuation
      of acoustic beam not only depends on the turbulence but also depends on the
      application parameters such as the beam width, the beam orientation and whether
      for forward propagation or back scatter propagation. Analysis shows that the
      excess attenuation appears to have a frequency dependence of cube-root. The
      expression for the excess attenuation coefficient has been used in the
      estimations of the temperature structure coefficient, C(T)2, in sodar sounding.
      The correction of C(T)2 values for excess attenuation reduces their errors
      greatly. Published profiles of temperature structure coefficient and the velocity
      structure coefficient in convective conditions are used to test our theory, which
      is compared with the theory by Brown and Clifford. The excess attenuation due to
      scattering from turbulence and atmospheric absorption are both taken into account
      in sodar data processing for deducing the contribution of the lower atmosphere to
      seeing, which is the sharpness of a telescope image determined by the degree of
      turbulence in the Earth's atmosphere. The comparison between the contributions of
      the lowest 300-m layer to seeing with that of the whole atmosphere supports the
      reasonableness of our estimation of excess attenuation.

PMID- 14714793
TI  - On the sound field from a moving source in a viscous medium.
AB  - Based on a one-dimensional model, a wave-theoretic analysis of the sound field
      from a moving, harmonic source in a viscous medium is developed. When the source
      is inbound to the receiver, the field consists of an attenuated propagating wave
      with Doppler up-shifted frequency. A similar wave is present when the source is
      outbound from the receiver but with down-shifted frequency. Also present on the
      outbound run is an evanescent wave that appears at the instant the source passes
      the receiver. The evanescent wave is very highly attenuated and exists only in
      the presence of both source motion and dissipation. Expressions are formulated
      for the frequency and attenuation coefficient of the two propagating waves and
      the evanescent wave. The attenuation of the propagating waves scales with the
      square of the frequency, which is a characteristic of viscous dissipation; and
      the attenuation is strongly asymmetrical, being significantly higher on approach
      than departure. The asymmetry in the attenuation arises partly from the upward
      and downward Doppler shifts in the frequency on approach and departure,
      respectively. In addition, the attenuation is skewed by the factor (1 +/- beta)(
      1), where the lower (upper) sign applies on approach (departure) and beta is the
      Mach number of the source. At a Mach number of 0.85, the ratio of the inbound to
      outbound attenuation is 2000.

PMID- 14714794
TI  - Coupled perturbed modes over a sloping penetrable bottom.
AB  - The development of coupled perturbed mode theory--the combination of conventional
      coupled modes and perturbation theory for problems of sound speed range
      dependence--is extended using a transformation of the normal modes to include a
      range-dependent penetrable bottom. The result is a fast, direct, and accurate
      range-dependent modal solution of the acoustic field in the water column. The
      method is applied to upslope propagation in shallow water wedge waveguides.

PMID- 14714795
TI  - Effect of ocean currents on the performance of a time-reversing array in shallow
      water.
AB  - Active acoustic time reversal may be accomplished by recording sounds with an
      array of transducers--a time-reversing array (TRA) or time-reversal mirror (TRM)-
      and then replaying the recorded and time-reversed sounds from the same array to
      produce back-propagating waves that converge at the location(s) of the remote
      sound source(s). Future active sonar and underwater communication systems
      suitable for use in unknown shallow ocean waters may be developed from the
      automatic spatial and temporal focusing properties of TRAs. However, ocean
      currents affect time reversal because they alter acoustic reciprocity in the
      environment. This paper presents a theoretical and computational investigation
      into how ocean currents influence TRA retrofocusing in shallow ocean environments
      for various array orientations. The case of TRA retrofocusing in a three
      dimensional range-independent sound channel with a steady horizontal ocean
      current is covered here, based on a normal-mode propagation model valid for low
      Mach number currents. The main finding is that in the presence of ocean currents
      (typically <1 m/s), a TRA performs well (the associated retrofocus amplitude
      decay is less than 1 dB) except that a retrofocus shift (up to a few wavelengths
      at 500 Hz at a range of 2.5 km) may occur due to the differing interaction
      between the ocean current profile and each acoustic normal mode. In addition, TRA
      performance is predicted to depend on the array orientation relative to the ocean
      current direction, especially for horizontal arrays.

PMID- 14714796
TI  - Depth-dependent target strengths of gadoids by the boundary-element method.
AB  - The depth dependence of fish target strength has mostly eluded experimental
      investigation because of the need to distinguish it from depth-dependent
      behavioral effects, which may change the orientation distribution. The boundary
      element method (BEM) offers an avenue of approach. Based on detailed morphometric
      data on 15 gadoid swimbladders, the BEM has been exercised to determine how the
      orientation dependence of target strength changes with pressure under the
      assumption that the fish swimbladder remains constant in shape and volume. The
      backscattering cross section has been computed at a nominal frequency of 38 kHz
      as a function of orientation for each of three pressures: 1, 11, and 51 atm.
      Increased variability in target strength and more abundant and stronger
      resonances are both observed with increasing depth. The respective backscattering
      cross sections have been averaged with respect to each of four normal
      distributions of tilt angle, and the corresponding target strengths have been
      regressed on the logarithm of fish length. The tilt-angle-averaged backscattering
      cross sections at the highest pressure have also been averaged with respect to
      frequency over a 2-kHz band for representative conditions of insonification. For
      all averaging methods, the mean target strength changes only slightly with depth.

PMID- 14714797
TI  - Blind prediction of broadband coherence time at basin scales.
AB  - A blind comparison with data is made with a model for the coherence time of
      broadband sound (133 Hz, 17-Hz bandwidth) at 3709 km. Coherence time is limited
      by changes in the ocean because the acoustic instruments are fixed to the Earth
      on the bottom of the sea with time bases maintained by atomic clocks. Although
      the modeled coherence time depends a bit on the difficult problem of correctly
      modeling relative signal-to-noise ratios, normalized correlation coefficients of
      the broadband signals for the data (model) are 0.90 (0.83), 0.72 (0.59), and 0.51
      (0.36) at lags of 2, 4.1, and 6.2 min, respectively. In all these cases, observed
      coherence times are a bit longer than modeled. The temporal evolution of the
      model is based on the linear dispersion relation for internal waves. Acoustic
      propagation is modeled with the parabolic approximation and the sound-speed
      insensitive operator.

PMID- 14714798
TI  - Equivalence of Gaussian and piston ultrasonic transducer voltages.
AB  - A plane-wave decomposition of collimated beams and electromechanical reciprocity
      relations are used to demonstrate fundamental differences and unusual
      similarities about transducer fields and transducer voltages at ultrasonic
      frequencies under various conditions. It is shown that the voltage induced by a
      transmitting acoustic piston transducer (constant particle velocity over the
      transducer surface) radiating into an ideal fluid medium on a second identical
      piston transducer, operating as a receiver, is nearly identical to the voltage
      observed when the two transducers have instead a Gaussian radial surface velocity
      distribution. The strong similarity in induced voltage begins when the two
      devices are separated by only several acoustic wavelengths, still well within the
      nearfield of both transducers, and the similarity increases with separation.
      Cases of transducer velocity distributions different from piston, such as
      Lorentzian or triangular, yield results nearly identical to the piston case.
      Transducers of differing size are also treated. It is further shown that an
      "equivalent transducer" can be derived for any combination of radiators, whose
      field is identical to the voltage measured using the pair. Moreover, with this
      concept the calculation of voltage in two-probe experiments is as simple as well
      known approximations to the Rayleigh integral for a single transducer. These
      results have substantial consequences for calculations, either analytical or
      numerical, that predict the voltage measured in two-transducer experiments.

PMID- 14714799
TI  - Gas-phase generation of photoacoustic sound in an open environment.
AB  - The photoacoustic effect is commonly exploited for molecular spectroscopy,
      nondestructive evaluation, and trace gas detection. Photoacoustic sound is
      produced when a photoactive material absorbs electromagnetic radiation and
      converts it to acoustic waves. This article focuses on the generation of
      photoacoustic sound from thermal expansion of photoactive gases due to unsteady
      heating from a laser light source, and extends the work of prior studies on
      photoacoustic sound generation in an open environment. Starting with the forced
      free-space wave equation, a simple model is constructed for photoacoustic sounds
      produced by both acoustically distributed and compact gas clouds. The model
      accounts for laser absorption through the Lambert-Beer law and includes the
      effects of photoactive gas cloud characteristics (shape, size, and concentration
      distribution), but does not include molecular diffusion, thermal conduction,
      convection, or the effects of acoustic propagation through sound-absorbing
      inhomogeneous media. This model is compared to experimentally measured
      photoacoustic sounds generated by scanning a 10.6-micron carbon dioxide (CO2)
      laser beam through small clouds of a photoactive gas, sulfur hexafluoride (SF6).
      For the current investigation, the photoactive gas clouds are formed either by
      low flow-rate calibrated leak sources or by a laminar jet emerging from a 1.6-mm
      diam tube. Model-measurement comparisons are presented over a 3- to 160-kHz
      bandwidth. Signal pulse shapes from simple gas cloud geometries are found to
      match calculated results when unmeasured gas cloud characteristics within the
      model are adjusted.

PMID- 14714800
TI  - A Wiener filter approach to the binaural reproduction of stereo sound.
AB  - This paper considers authentic binaural reproduction with loudspeakers using
      cross-talk cancellation. A systematic time domain deconvolution method is
      presented using both stochastic and deterministic Wiener filters. This method has
      advantages in that the Wiener filter is inherently causal and stable so that no
      additional stabilization process, as generally required in the frequency domain
      methods, is needed. Errors involved in the authentic reproduction are classified
      into modeling, inverse, and repeatability errors. In addition, the reproduction
      error is used as the performance measure of a reproduction system. Finally, a
      series of monaural and binaural reproduction tests were conducted in an anechoic
      chamber using a PC based reproduction system with a soundcard by changing the
      length of the inverse filter used. Test results demonstrated that the performance
      was improved in proportion to the length of the filter used. The reproduction
      performance error and its test procedure presented here can be used for
      objectively assessing the performance of a subjective auditory perception test
      system.

PMID- 14714801
TI  - Characterizing computer cooling fan noise.
AB  - Computer cooling fan noise is studied theoretically, focusing on the radiation
      from the interaction between rotor blades and motor struts. The source is
      decomposed into axial thrust, circumferential drag, and radial force. There is no
      sound-power coupling among the three components. The index of spatial spinning
      pressure mode plays the key role in noise radiation. The leading modes are the
      zeroth, or coincident, mode for thrust and the first mode for the drag and radial
      force. The effect of source noncompactness is quantified and found to be
      substantial only for higher-order radiation modes. The sound powers of the
      leading modes follow a sixth-power law, while the next high-order modes follow an
      eighth-power law. Quantitative analysis shows that the drag force can be equally
      noisy as the coincident thrust force. Based on an empirical aerodynamic model of
      rotor-strut interaction, it is found that the total sound power is more sensitive
      to the number of struts than rotor blades. Numerical examples are given to
      demonstrate how the struts can be optimized for typical cooling fan conditions.

PMID- 14714802
TI  - Active local control of propeller-aircraft run-up noise.
AB  - Engine run-ups are part of the regular maintenance schedule at Vancouver
      International Airport. The noise generated by the run-ups propagates into
      neighboring communities, disturbing the residents. Active noise control is a
      potentially cost-effective alternative to passive methods, such as enclosures.
      Propeller aircraft generate low-frequency tonal noise that is highly compatible
      with active control. This paper presents a preliminary investigation of the
      feasibility and effectiveness of controlling run-up noise from propeller aircraft
      using local active control. Computer simulations for different configurations of
      multi-channel active-noise-control systems, aimed at reducing run-up noise in
      adjacent residential areas using a local-control strategy, were performed. These
      were based on an optimal configuration of a single-channel control system studied
      previously. The variations of the attenuation and amplification zones with the
      number of control channels, and with source/control-system geometry, were
      studied. Here, the aircraft was modeled using one or two sources, with monopole
      or multipole radiation patterns. Both free-field and half-space conditions were
      considered: for the configurations studied, results were similar in the two
      cases. In both cases, large triangular quiet zones, with local attenuations of 10
      dB or more, were obtained when nine or more control channels were used. Increases
      of noise were predicted outside of these areas, but these were minimized as more
      control channels were employed. By combining predicted attenuations with measured
      noise spectra, noise levels after implementation of an active control system were
      estimated.

PMID- 14714803
TI  - Low-frequency absorption using a two-layer system with active control of input
      impedance.
AB  - Broadband noise absorption, including low frequencies, may be obtained by a
      hybrid passive-active two-layer system. A porous layer in front of an air layer
      provides passive absorption, at medium and high frequencies. Active control of
      the input impedance of the two-layer system yields absorption at low frequencies.
      The active control system can implement either pressure-release or impedance
      matching conditions. A simple analytical model based upon plane waves propagating
      in a tube permits the comparison of both control strategies. The results of this
      simple model show that the pressure-release condition affords higher absorption
      than the impedance-matching condition for some combinations of geometrical and
      material parameters. Experimental results corroborate the good performance of the
      pressure-release condition under the prescribed geometrical setup.

PMID- 14714804
TI  - Energy transmittance predicts conductive hearing loss in older children and
      adults.
AB  - The test performance of a wideband acoustic transfer function (ATF) test and 226
      Hz tympanometry was assessed in predicting the presence of conductive hearing
      loss, based on an air-bone gap of 20 dB or more. Two ATF tests were designed
      using an improved calibration method over a frequency range (0.25-8 kHz): an
      ambient-pressure test and a tympanometric test using an excess static pressure in
      the ear canal. Wideband responses were objectively classified using moment
      analyses of energy transmittance, which was a more appropriate test variable than
      energy reflectance. Subjects included adults and children of age 10 years and up,
      with 42 normal-functioning ears and 18 ears with a conductive hearing loss.
      Predictors were based on the magnitudes of the moment deviations from the 10th to
      90th percentiles of the normal group. Comparing tests at a fixed specificity of
      0.90, the sensitivities were 0.28 for peak-compensated static acoustic admittance
      at 226 Hz, 0.72 for ambient-pressure ATF, and 0.94 for pressurized ATF.
      Pressurized ATF was accurate at predicting conductive hearing loss with an area
      under the receiver operating characteristic curve of 0.95. Ambient-pressure ATF
      may have sufficient accuracy to use in some hearing-screening applications,
      whereas pressurized ATF has additional accuracy that may be appropriate for
      hearing-diagnostic applications.

PMID- 14714805
TI  - A longitudinal study of distortion product otoacoustic emission ipsilateral
      suppression and input/output characteristics in human neonates.
AB  - Past work has shown that distortion product otoacoustic emission (DPOAE) (2f1-f2)
      ipsilateral suppression and input/output (I/O) characteristics are not adult-like
      in prematurely born neonates [Abdala, J. Acoust. Soc. Am. 110, 1465-1476 (2001)].
      These age differences are most pronounced at f2 = 6000 Hz and have been
      interpreted to indicate a subtle immaturity in human cochlear function prior to
      term birth. It is still not clear, however, whether term-born neonates are
      completely adult-like in cochlear function. To study this question, DPOAE
      suppression and I/O functions for f2 = 6000 Hz were measured in a group of
      prematurely born neonates at weekly intervals over a period of 7-8-weeks, a group
      of normal-hearing adults, and during a one-time test session in a group of term
      born neonates. Results show that there was no significant change in suppression
      tuning, suppression growth, and various I/O characteristics across test session
      for premature neonates, but there was an age-group effect; even once prematurely
      born neonates reached the equivalence of term-like status (38-40-weeks
      postconceptional weeks), they continued to show narrower suppression tuning than
      adults, shallower suppression growth for low-frequency side suppressor tones, and
      an elevated amplitude saturation plateau on the I/O function. Term-born neonates
      showed DPOAE results that were comparable to those measured from premature
      neonates and unlike adult findings. These results suggest that a subtle
      immaturity in cochlear function persists into the postnatal period.

PMID- 14714806
TI  - Influence of hearing sensitivity on mechano-electric transduction.
AB  - This study examined the relation between the extent of permanent hearing loss and
      the change in a third-order polynomial transducer function (PTF) representing
      mechano-electric transduction (MET). Mongolian gerbils were exposed to noise for
      1 to 128 h. A control group received no exposure. The cochlear microphonic (CM)
      was recorded from a round-window electrode and stapes velocity was recorded with
      a laser Doppler vibrometer in response to Gaussian noise. A nonlinear systems
      identification procedure provided the frequency-domain coefficients of the PTF
      and their associated coherence functions. In the control group, the PTF in the
      high frequencies was dominated by linear and cubic terms. In noise-exposed
      animals, the magnitude of these terms decreased with increasing threshold,
      suggesting a progressive decrease in the receptor currents through basal hair
      cells. Moreover, the linear coherence increased and the cubic coherence
      decreased, indicating that MET in the cochlear base became linear. In the low
      frequencies, noise exposure altered the group delay of the CM, demonstrating a
      redistribution of hair-cell currents. The low-frequency PTF was characterized by
      an increase in the contribution in the quadratic term. With increasing threshold,
      the slope of the PTF decreased and the saturation for positive CM was eliminated.

PMID- 14714807
TI  - A short latency vestibular evoked potential (VsEP) produced by bone-conducted
      acoustic stimulation.
AB  - In this paper data are presented from an experiment which provides evidence for
      the existence of a short latency, acoustically evoked potential of probable
      vestibular origin. The experiment was conducted in two phases using bone
      conducted acoustic stimulation. In the first phase subjects were stimulated with
      6-ms, 500-Hz tone bursts in order to obtain the threshold V(T) for vestibular
      evoked myogenic potentials (VEMP). It was confirmed that the difference between
      bone-conducted auditory and acoustic vestibular thresholds was slightly over 30
      dB. The estimated threshold was then used as a reference value in the second part
      of the experiment to stimulate subjects over a range of intensities from -6 to
      +18 dB (re: V(T)). Averaged EEG recordings were made with eight Ag/AgCl
      electrodes placed on the scalp at Fpz, F3, F4, F7, F8, Cz, T3, and T4 according
      to the 10-20 system. Below V(T) auditory midlatency responses (MLRs) were
      observed. Above V(T) two additional potentials appeared: a positivity at about 10
      ms (P10) which was maximal at Cz, and a negativity at about 15 ms (N15) which was
      maximal at Fpz. Extrapolation of the growth functions for the P10 and N15
      indicated a threshold close to V(T), consistent with a vestibular origin of these
      potentials. Given the low threshold of vestibular acoustic sensitivity it is
      possible that this mode may make a contribution to the detection of and affective
      responses to loud low frequency sounds. The evoked potentials may also have
      application as a noninvasive and nontraumatic test of vestibular projections to
      the cortex.

PMID- 14714808
TI  - Psychometric functions for informational masking.
AB  - The term informational masking has traditionally been used to refer to elevations
      in signal threshold resulting from masker uncertainty. In the present study, the
      method of constant stimuli was used to obtain complete psychometric functions
      (PFs) from 44 normal-hearing listeners in conditions known to produce varying
      amounts of informational masking. The listener's task was to detect a pure-tone
      signal in the presence of a broadband noise masker (low masker uncertainty) and
      in the presence of multitone maskers with frequencies and amplitudes that varied
      at random from one presentation to the next (high masker uncertainty). Relative
      to the broadband noise condition, significant reductions were observed in both
      the slope and the upper asymptote of the PF for multitone maskers producing large
      amounts of informational masking. Slope was affected more for some listeners and
      conditions while asymptote was affected more for others; consequently, neither
      parameter alone was highly predictive of individual thresholds or the amount of
      informational masking. Mean slopes and asymptotes varied nonmonotonically with
      the number of masker components in a manner similar to mean thresholds,
      particularly when the estimated effect of energetic masking on thresholds was
      subtracted out. As in past studies, the threshold data were well described by a
      model in which trial-by-trial judgments are based on a weighted sum of levels in
      dB at the output of independent auditory filters. The psychometric data, however,
      complicated the model's interpretation in two ways: First, they suggested that,
      depending on the listener and condition, the weights can either reflect a fixed
      influence of masker components on each trial or the effect of occasionally
      mistaking a masker component for the signal from trial to trial. Second, they
      indicated that in either case the variance of the underlying decision variable as
      estimated from PF slope is not by itself great enough to account for the observed
      changes in informational masking.

PMID- 14714809
TI  - Tone decay for hearing-impaired listeners with and without dead regions in the
      cochlea.
AB  - For people with normal hearing, a sustained tone with a frequency within the
      standard audiometric range remains audible when presented at a level well above
      threshold. However, for a pure tone with frequency close to the upper limit of
      hearing (well above 8 kHz), the loudness may decrease within seconds and the tone
      may decay to inaudibility, even when presented at a level between 20 and 40 dB
      SL. Scharf [in Hearing Research and Theory, edited by J. V. Tobias and E. D.
      Schubert (Academic, New York, 1983), Vol. 2, pp. 1-53] suggested that marked
      loudness adaptation only occurs when the excitation pattern evoked by a tone is
      spatially limited. The upper limit of hearing may be comparable to the boundary
      of a "dead region," which is a region with a complete loss of inner hair cell
      (IHC) and/or neural function. The present study investigated the perceived decay
      of pure tones for 9 normal-hearing subjects and 12 subjects with moderate to
      severe sensorineural hearing loss, using a wide range of frequencies (0.125-12
      kHz). A dead region was diagnosed for 8 of the 12 subjects. No consistent
      association was found between the degree of tone decay and the presence of a dead
      region. Subjects with dead regions did not experience significantly more tone
      decay than subjects with comparable absolute thresholds but without a dead
      region, even when the frequency of the tone fell within or close to the edge of a
      dead region. For severely hearing-impaired subjects, spatial restriction of the
      excitation pattern was neither necessary nor sufficient to lead to tone decay.
      The prevalence of tone decay was not well predicted by the audiometric threshold
      at the test frequency. It is proposed that tone decay depends on the
      physiological condition of the place in the cochlea where the tone is detected,
      which, in a case involving a dead region, is the place adjacent to the dead
      region. The prevalence of tone decay increased when the audiometric threshold was
      above 50 dB HL in the frequency region where the tone was detected.

PMID- 14714810
TI  - Temporal masking of multidimensional tactual stimuli.
AB  - Experiments were performed to examine the temporal masking properties of
      multidimensional tactual stimulation patterns delivered to the left index finger.
      The stimuli consisted of fixed-frequency sinusoidal motions in the kinesthetic (2
      or 4 Hz), midfrequency (30 Hz), and cutaneous (300 Hz) frequency ranges. Seven
      stimuli composed of one, two, or three spectral components were constructed at
      each of two signal durations (125 or 250 ms). Subjects identified target signals
      under three different masking paradigms: forward masking, backward masking, and
      sandwiched masking (in which the target is presented between two maskers). Target
      identification was studied as a function of interstimulus interval (ISI) in the
      range 0 to 640 ms. For both signal durations, percent-correct scores increased
      with ISI for each of the three masking paradigms. Scores with forward and
      backward masking were similar and significantly higher than scores obtained with
      sandwiched masking. Analyses of error trials revealed that subjects showed a
      tendency to respond, more often than chance, with the masker, the composite of
      the masker and target, or the combination of the target and a component of the
      masker. The current results are compared to those obtained in previous studies of
      tactual recognition masking with brief cutaneous spatial patterns. The results
      are also discussed in terms of estimates of information transfer (IT) and IT
      rate, are compared to previous studies with multidimensional tactual signals, and
      are related to research on the development of tactual aids for the deaf.

PMID- 14714811
TI  - Factors affecting the duration effect in pitch perception for unresolved complex
      tones.
AB  - Previous research has shown that fundamental frequency (F0) discrimination
      thresholds for complex tones containing unresolved harmonics decrease as the
      duration of the tone increases [White and Plack, J. Acoust. Soc. Am. 103, 2051
      2063 (1998)]. In this paper F0 discrimination was measured as a function of
      duration for complexes with F0s of 62.5, 125, and 250 Hz, bandpass filtered into
      two spectral regions (2750-3750 and 5500-7500 Hz). The harmonics were summed
      either in sine phase (SINE) or with alternating sine-cosine phase (ALT), which
      affects the envelope of the waveform and the pitch of the complex. Tone duration
      was 20, 40, 80, and 160 ms. The improvement in F0 discrimination with duration
      increased with decreasing F0. When harmonics where spectrally filtered between
      2750 and 3750 Hz, for complexes with an F0 of 62.5 Hz, F0 discrimination
      thresholds decreased from approximately 30% for a 20-ms tone to approximately 3%
      for a 160-ms tone. For complexes with an F0 of 250 Hz, thresholds decreased from
      3% for a 20-ms tone to 1% for a 160-ms tone: a lower envelope repetition rate led
      to a larger change in performance with increasing duration. The phase
      manipulation also affected the size of the duration effect, in that the effect
      was less for an ALT complex compared to a SINE complex with the same F0,
      consistent with the change in envelope repetition rate. Overall, the results
      suggest that for unresolved complex tones it is primarily envelope repetition
      rate, not spectral region, that determines both the F0 discrimination threshold
      and the size of the duration effect.

PMID- 14714812
TI  - Binaural models and the strength of dichotic pitches.
AB  - Modern physiologically based models of the binaural system incorporate internal
      delay lines in the pathways from left and right peripheries to central processing
      nuclei. Different binaural models for the formation of dichotic pitch employ
      these delay lines in different ways. Consequently, the different models make
      different predictions for the relative strengths of dichotic pitches made with
      particular phase conditions. The differences are magnified for dichotic pitches
      at low frequencies where especially long delay lines may be required. Data from
      four low-frequency pitch strength experiments on pure-tone-like dichotic pitches
      (two on Huggins pitch and two on binaural coherence edge pitch) are consistent
      with models of the equalization-cancellation type and not consistent with the
      central activity pattern model.

PMID- 14714813
TI  - High-rate conditioning pulse trains in cochlear implants: dynamic range measures
      with sinusoidal stimuli.
AB  - The addition of a continuous, unmodulated, high-rate pulse train to the
      electrical signals of cochlear implant recipients results in statistically
      significant increases in psychophysical dynamic range (41 out of 46 electrode
      pairs tested). The observed increases in dynamic range are thought to result from
      nerve conditioning by appropriate levels of high-rate pulse train. Five dynamic
      range profiles are characterized, defining the different responses of dynamic
      range observed with increasing levels of the conditioner. Four of the five
      profiles demonstrate increases in dynamic range, with three showing behavior
      consistent with stochastic resonance. One profile depicts evidence of adaptation
      in response to higher levels of the conditioner, with a recovery period lasting
      throughout the duration (on the scale of tens of minutes) of experimentation.
      Dynamic range profiles are shown to be similar across sinusoidal frequencies
      (202, 515, and 1031 Hz) but potentially different across electrode pairs
      (electrodes 1-2, 7-8, and 15-16). Correlation analysis does not reveal any
      predictors of optimal conditioner level or amount of dynamic range increase with
      the conditioner.

PMID- 14714814
TI  - Respiratory constraints on speech production: starting an utterance.
AB  - The aim of this research is to model the sequences of respiratory and
      articulatory events that occur when a speaker starts talking. In this paper, the
      focus is placed on a set of timing landmarks--utterance onset, phonation onset,
      and the initial peak in subglottal pressure--in relation to the first sound
      segment in the utterance and the location of the first syllable in the utterance
      that is judged as prominent by a listening panel. Simultaneous recordings of the
      acoustic signal, airflow, lung volume, and subglottal pressure as estimated from
      esophageal pressure were collected from four native speakers of American English.
      The timing of the initial alveolar pressure peak generally coincides with a
      prominent syllable if that syllable is the first or second syllable in the
      utterance, and precedes later prominences. There is considerable scatter in
      phonation pressure and phonation onset time across speakers and utterances.
      Normalizing these parameters to the initial pressure peak provides a more
      coherent view of the pressure trajectory and the influence of the initial sound
      segment on phonation parameters. Use of the data in the development of a model of
      the respiratory system during speech is discussed.

PMID- 14714815
TI  - Influence of collision on the flow through in-vitro rigid models of the vocal
      folds.
AB  - Measurements of pressure in oscillating rigid replicas of vocal folds are
      presented. The pressure upstream of the replica is used as input to various
      theoretical approximations to predict the pressure within the glottis. As the
      vocal folds collide the classical quasisteady boundary layer theory fails. It
      appears however that for physiologically reasonable shapes of the replicas,
      viscous effects are more important than the influence of the flow unsteadiness
      due to the wall movement. A simple model based on a quasisteady Bernoulli
      equation corrected for viscous effect, combined with a simple boundary layer
      separation model does globally predict the observed pressure behavior.

PMID- 14714816
TI  - Schlieren imaging of shock waves from a trumpet.
AB  - A sensitive, large-aperture schlieren optical instrument is applied to observe
      gas-dynamic phenomena at the exit of a trumpet. Shock waves are seen, especially
      for loud, high-pitched trumpet notes, and several illustrations are given.
      Microphone waveforms are given for representative examples. These shock waves
      arise from the shock-tube-like effect of the performer's intermittent breath
      pressure driving the cylindrical duct of the trumpet, and are the result of
      cumulative nonlinear acoustic propagation inside the trumpet bore. They are,
      however, very weak, traveling only marginally above the acoustic speed. In the
      118-124 peak dB(A) range, they are near the weak limit of shock wave visibility
      by schlieren optics. The schlieren evidence confirms that the frequency of the
      emitted shock waves corresponds to the frequency of the note being played.
      Ancillary laminar and turbulent jet phenomena associated with the performer's
      breath are also visible in the images.

PMID- 14714817
TI  - Time-domain simulation of a guitar: model and method.
AB  - This paper presents a three-dimensional time-domain numerical model of the
      vibration and acoustic radiation from a guitar. The model involves the transverse
      displacement of the string excited by a force pulse, the flexural motion of the
      soundboard, and the sound radiation. A specific spectral method is used for
      solving the Kirchhoff-Love's dynamic top plate model for a damped, heterogeneous
      orthotropic material. The air-plate interaction is solved with a fictitious
      domain method, and a conservative scheme is used for the time discretization.
      Frequency analysis is performed on the simulated sound pressure and plate
      velocity waveforms in order to evaluate quantitatively the transfer of energy
      through the various components of the coupled system: from the string to the
      soundboard and from the soundboard to the air. The effects of some structural
      changes in soundboard thickness and cavity volume on the produced sounds are
      presented and discussed. Simulations of the same guitar in three different cases
      are also performed: "in vacuo," in air with a perfectly rigid top plate, and in
      air with an elastic top plate. This allows comparisons between structural,
      acoustic, and structural-acoustic modes of the instrument. Finally, attention is
      paid to the evolution with time of the spatial pressure field. This shows, in
      particular, the complex evolution of the directivity pattern in the near field of
      the instrument, especially during the attack.

PMID- 14714818
TI  - Impedance measurements of ex vivo rat lung at different volumes of inflation.
AB  - A previous study [J. Acoust. Soc. Am. 111, 1102-1109 (2002)] showed that the
      occurrence of ultrasonically induced lung hemorrhage in rats was directly
      correlated to the level of lung inflation. In that study, it was hypothesized
      that the lung could be modeled as two components consisting of air and parenchyma
      (contiguous tissue [pleura and septa]). The speed of sound and lung impedance
      would then depend on the fractional volume of air in the lung. According to that
      model, an inflated lung should act like a pressure-release surface for sound
      incident from tissue onto a tissue-lung boundary. A deflated lung containing less
      air should allow more acoustic energy into the lung tissue because the impedance
      was more closely matched to the contiguous tissues. In the study reported herein,
      a measurement technique was devised to calculate the impedance of seven rat
      lungs, ex vivo, under deflation (atmospheric pressure) and three volumes of
      inflation pressure (7-cm H2O, 10-cm H2O, and 15-cm H2O). Lungs were dissected
      from rats and immediately scanned in a tank of degassed 37 degrees C water. The
      frequency-dependent acoustic pressure reflection coefficient was measured over a
      frequency range of 3.5 to 10 MHz. From the reflection coefficient, the frequency
      dependent lung impedance was calculated with values ranging from an average of 1
      Mrayls in deflated lungs to 0.2 Mrayls for fully inflated lungs. Lung impedance
      calculations showed that deflated lungs had an impedance closer to water (1.52
      Mrayls) than inflated lungs. At all volumes of inflation, the lungs acted as
      pressure-release surfaces relative to the water. The average of the four lung
      impedance values (deflated, 7-cm H2O, 10-cm H2O, and 15-cm H2O) at each level of
      inflation was statistically different (p<0.0001).

PMID- 14714819
TI  - Modulation spectra of natural sounds and ethological theories of auditory
      processing.
AB  - The modulation statistics of natural sound ensembles were analyzed by calculating
      the probability distributions of the amplitude envelope of the sounds and their
      time-frequency correlations given by the modulation spectra. These modulation
      spectra were obtained by calculating the two-dimensional Fourier transform of the
      autocorrelation matrix of the sound stimulus in its spectrographic
      representation. Since temporal bandwidth and spectral bandwidth are conjugate
      variables, it is shown that the joint modulation spectrum of sound occupies a
      restricted space: sounds cannot have rapid temporal and spectral modulations
      simultaneously. Within this restricted space, it is shown that natural sounds
      have a characteristic signature. Natural sounds, in general, are low-passed,
      showing most of their modulation energy for low temporal and spectral
      modulations. Animal vocalizations and human speech are further characterized by
      the fact that most of the spectral modulation power is found only for low
      temporal modulation. Similarly, the distribution of the amplitude envelopes also
      exhibits characteristic shapes for natural sounds, reflecting the high
      probability of epochs with no sound, systematic differences across frequencies,
      and a relatively uniform distribution for the log of the amplitudes for
      vocalizations. It is postulated that the auditory system as well as engineering
      applications may exploit these statistical properties to obtain an efficient
      representation of behaviorally relevant sounds. To test such a hypothesis we show
      how to create synthetic sounds with first and second order envelope statistics
      identical to those found in natural sounds.

PMID- 14714820
TI  - Acoustic variability and distinguishability among mouse ultrasound vocalizations.
AB  - Auditory neurobiology has benefited significantly from ethological approaches
      using acoustic communication signals. Developing an ethological model in a
      genetically manipulable system such as the mouse would enhance the ability to
      investigate the processing, learning, and recognition of sounds. Characterizing
      the basic acoustic structure of mouse vocalizations would help lay a foundation
      for such a future study. Towards this goal, ultrasound vocalizations emitted by
      isolated mouse pups and pairs of adult males and females have been digitally
      recorded and examined. Previous work suggests that these calls may have
      communicative significance. An analysis of the natural variability in their
      spectral content, median frequency, duration, and repetition period reveals
      acoustic structure that could be used for recognizing the calls. Other
      parameters, like the rate of frequency modulation, may also be informative, but
      have not been examined. Pup isolation calls develop systematically between
      postnatal day 5 and 12 towards a more stereotyped vocalization--contracting from
      a wide range of values into narrower clusters of frequency and duration, and
      shifting from longer to shorter repetition periods. Most significantly, pup
      isolation and adult encounter calls fall into two distinct spectral and temporal
      categories, making it possible for a receiver to acoustically distinguish between
      them, and to potentially categorically perceive them along those dimensions.

PMID- 14714821
TI  - The new H.F.E.A. alert system.

PMID- 14714822
TI  - Analyzing factors affecting the success rate of frozen-thawed embryos.
AB  - PURPOSE: In recent years the infertile population applying for IVF treatments was
      changed and so the indications for performing intracellular sperm injection
      (ICSI). The aim of this study was to analyze predicting factors of our thawing
      cycles. METHODS: From December 1998 to July 2001, 440 consecutive thawing cycles
      were performed. Patient characteristics were examined. The number of
      cryopreserved embryos, number of transferred embryos, the timing of
      cryopreservation (48 h vs. 72 h), and embryo survival rate were analyzed as a
      possible predictor for pregnancies achievement. RESULTS: Conventional IVF
      patient's characteristic was significantly different from ICSI population and
      analysis has been performed for every population separately. In the IVF
      population the women age, the number of transferred embryos, and timing of
      cryopreservation were factors significantly influencing the pregnancy rate.
      Interestingly, in the ICSI population only the number of transferred embryos was
      found to be a predictive factor. CONCLUSION: ICSI and IVF cycles should be
      analyzed separately. Not all the factors influencing the success rate in the
      conventional IVF population are valid in the ICSI population.

PMID- 14714823
TI  - Embryonic production of nitric oxide and its role in implantation: a pilot study.
AB  - PURPOSE: To investigate the ability of human embryos to produce nitric oxide (NO)
      and correlate its production with embryo quality and pregnancy rate. METHODS:
      Twenty-three women participated in the study and were submitted to controlled
      ovarian stimulation and intracytoplasmic sperm injection. Embryos were singularly
      cultured in medium microdrops of 50 microL and were replaced, by transcervical
      transfer, at the 2- to 6-cell stage. In the culture media of each embryo the NO
      production was assessed by monitoring the levels of its stable oxidation products
      (nitrites/nitrates). RESULTS: All the 23 patients underwent embryo transfer.
      After microinjection 64 embryos were obtained. The mean number of transferred
      embryos was 2.61 +/- 0.46 and the pregnancy rate was 26%. The mean
      nitrite/nitrate concentrations of culture medium of each embryo was significantly
      higher (5.88 +/- 2.34 micromol/L) than in pure P-1 medium (0.81 +/- 0.21
      micromol/L; p < 0.001) demonstrating an embryonic secretion of NO. Comparing
      pregnant (7.34 +/- 2.72 micromol/L) versus nonpregnant patients (5.53 +/- 1.49
      micromol/L; p = 0.022), the mean nitrite/nitrate concentrations were
      significantly higher. Furthermore, the best quality embryos of pregnant women
      produced significantly higher nitrite/nitrate concentrations than those of not
      pregnant patients. CONCLUSIONS: It seems that NO production in nidating embryos
      is increased and that it may be primarily associated with a better morphology and
      a better growth potential of developing embryos.

PMID- 14714824
TI  - Gonadotropin-releasing hormone (GnRH)-antagonist versus GnRH-agonist in ovarian
      stimulation of poor responders undergoing IVF.
AB  - PURPOSE: The objective of this study was to compare the efficacy of GnRH
      antagonists to GnRH-agonists in ovarian stimulation of poor responders undergoing
      IVF. METHODS: Retrospective analysis of our data revealed that 56 patients
      underwent treatment with a GnRH-agonist according to the flare-up protocol.
      Patients failing to achieve an ongoing pregnancy (n = 53) were subsequently
      treated in the next cycle with a GnRH-antagonist according to the multiple-dose
      protocol. Main outcome measures included the clinical pregnancy and implantation
      rates. RESULTS: While ovulation induction characteristics and results did not
      differ between the two protocols, the number of embryos transferred was
      significantly higher (P = 0.046) in the GnRH-antagonist than in the GnRH-agonist
      stimulation protocol (2.5 +/- 1.6 vs. 2.0 +/- 1.4, respectively). The clinical
      pregnancy and implantation rates per transfer in the GnRH-antagonist group
      appeared higher than in the GnRH-agonist, but did not differ statistically (26.1
      and 10.7 compared with 12.2 and 5.9%, respectively). However, the ongoing
      pregnancy rate per transfer was statistically significantly higher (P = 0.03) in
      the GnRH-antagonist than in the GnRH-agonist group (23.9 vs. 7.3%, respectively).
      CONCLUSION: Applying GnRH-antagonists to ovarian stimulation protocols may offer
      new hope for IVF poor responder patients. However, further controlled randomized
      prospective studies with larger sample sizes are required to establish these
      results.

PMID- 14714825
TI  - Consecutive transfer of day 3 embryos and of day 5-6 blastocysts increases
      overall pregnancy rates associated with blastocyst culture.
AB  - PURPOSE: To investigate whether the consecutive embryo transfer of day 3 embryos
      and of blastocyst protects against failure to reach embryo transfer and provides
      additional pregnancies. METHODS: An embryo transfer was performed on day 3
      following which all remaining embryos were cultured to the blastocyst stage for a
      possible second transfer. RESULTS: One hundred and forty-two patients were
      selected for extended culture. Thirty-two of these patients did not develop
      blastocysts in culture, however, there were 12 pregnancies achieved in this
      group. CONCLUSIONS: The consecutive transfer of day 3 embryos and blastocysts can
      prevent the total loss of a cycle when embryos fail to develop to the blastocyst
      stage in culture and thereby provide additional pregnancies.

PMID- 14714826
TI  - Endometrial pinopode and alphavbeta3 integrin expression is not impaired in
      infertile patients with endometriosis.
AB  - PURPOSE: To investigate endometrial receptivity in terms of pinopode formation
      and alphavbeta3 integrin expression in infertile women with endometriosis during
      natural cycles. METHODS: We investigated the expression of alphavbeta3 integrin
      and pinopode formation in the endometrium of 12 infertile patients with stage I
      or II endometriosis as the only cause of infertility, 12 infertile patients
      having unexplained infertility, and 12 fertile women who were undergoing tubal
      sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days
      later) were performed during a single menstrual cycle in each subject. RESULTS:
      No statistically significant difference regarding alphavbeta3 integrin expression
      and pinopode formation was found between infertile patients with endometriosis
      and the two control groups. CONCLUSION: alphavbeta3 integrin expression and
      pinopode formation are not reduced during the window of implantation in patients
      with stage I-II endometriosis. Whether these results imply normal endometrial
      receptivity in such patients or add to the increasing uncertainty about the
      clinical value of assessing the endometrium with those markers of implantation,
      warrants further studies.

PMID- 14714828
TI  - Expression of prostatic glutathione-peroxidase (GSH-PO) in the rat treated with a
      combination of testosterone and 17beta-estradiol.
AB  - In order to confirm the relationship between sex hormone administration and
      glutathione-peroxidase (GSH-PO) in the rat ventral prostate, the levels of GSH-PO
      mRNA, GSH-PO activity, and lipid peroxide (Thiobarbituric acid: TBA) value in the
      ventral prostate were investigated. Male Crj: CD (SD) IGS rats were divided into
      six experimental groups. Group 1 consisted of intact controls. In group 2, rats
      were sacrificed two days after castration. In groups 3 and 4, rats were
      subcutaneously administered 1 mg/animal of testosterone daily for three- or seven
      day administration two days after castration, respectively. In groups 5 and 6,
      rats were subcutaneously administered 1 mg/animal of testosterone plus 0.01
      mg/animal of 17beta-estradiol (E2) daily for three- or seven-day administration
      two days after castration, respectively. GSH-PO activity of the ventral prostate
      homogenate for testosterone or testosterone plus E2 administration to the
      castrated rat was increased and the TBA value was remarkably decreased. The
      prostatic GSH-PO mRNA level was diminished in the castrated rat ventral prostate,
      but was increased by testosterone or testosterone plus E2 administration. In
      particular, the GSH-PO mRNA level of testosterone plus E2-treated animals was
      higher than that of testosterone-treated animals. These findings strongly suggest
      that expression of GSH-PO in the rat ventral prostate is testosterone- or E2
      dependent. We speculate that the transcription of prostatic GSH-PO mRNA was
      regulated by testosterone or E2 and de novo synthesis of GSH-PO would thus be
      regulated at transcription level by testosterone or E2.

PMID- 14714827
TI  - Expression of transcription factors in endometrium during natural cycles.
AB  - PURPOSE: The sex steroid control of the endometrial cycle is mediated by
      transcription factors, four of which are the estrogen and progesterone receptors,
      c-jun and c-fos, all expressed by the endometrium. The aim of this study was to
      analyze the distribution of the transcription factors in the different
      endometrial compartments during natural cycles. METHODS: We studied 53
      reproductively-normal women, of whom 26 were in the proliferative phase and 27 in
      the secretory phase. An endometrial biopsy was performed and serum values of LH,
      FSH, estradiol, and progesterone were determined. We studied the expression of
      transcription factors using monoclonal antibodies. RESULTS: A correlation between
      estrogen receptor and c-jun and c-fos expression was observed in stroma and
      epithelia, and progesterone receptor expression correlated with c-jun expression
      in epithelia. C-jun and c-fos presented greater expression in the proliferative
      phase than in the secretory phase, in the stroma and in both epithelia. No
      relation was found between estradiol serum levels and any transcription factor,
      but progesterone serum levels correlated significantly with most such factors.
      CONCLUSION: The two proto-oncogenes could play a decisive role in regulating the
      endometrial cycle; they could mediate the effects induced by sex steroid, and
      could be related to other transcription factors.

PMID- 14714829
TI  - A case of type IV solar urticaria identified by reverse in vitro serum test.
AB  - We had a 17-year-old male patient with solar urticaria diagnosed as type IV of
      modified Harber's classification. The action spectrum of this case was estimated
      to be 433-499 nm and the inhibition spectrum was 533 nm. Both in vitro serum test
      and tentatively designated "reverse in vitro serum test" were positive. The
      patient was prescribed 20 mg/day epinastine hydrochloride (Alesion) orally for 49
      weeks with improvement of the symptoms.

PMID- 14714830
TI  - Immunohistochemical mucin expression of short-segment Barrett's esophagus.
AB  - Barrett's mucosa consists of metaplastic columnar epithelium (specialized
      columnar epithelium) of the esophagus. Recently, "short-segment Barrett's
      esophagus (SSBE)" was proposed. In the present study, we examined
      immunohistochemical mucin expression and the Ki-67 labeling index (LI) of SSBE,
      in 5-15 mm lengths. All 27 SSBE cases showed gastric mucin (MUC5AC, HGM, MUC6).
      CD10 and MUC2, which were markers of intestinal phenotypes, were detected in 13
      (48.1%) and 14 (51.9%) of the 27 SSBE cases. Ki-67 LI of SSBE positive cases for
      CD10 was 23.6 %, while that of SSBE negative cases for CD10 was 14.4 % (p <
      0.05). SSBE cases were divided into two groups: one was gastric epithelium type
      with low Ki-67 LI, and the other was metaplastic epithelium with intestinal
      metaplasia and high Ki-67 LI. The latter group was suggested to be more important
      as a premalignant lesion of esophageal adenocarcinoma.

PMID- 14714831
TI  - Urinary citrate in kidney stone disease.
AB  - BACKGROUND: Hypocitraturia, or low urinary citrate excretion is known as a risk
      for nephrolithiasis. Though urinary citrate excretion is basically determined by
      acid-base balance, metabolic acidosis is not always manifest in urinary stone
      patients with hypocitraturia. From our stone clinic data, we estimated the
      incidence of hypocitraturia and addressed its causes in the absence of obvious
      acid-base imbalance. METHODS: We selected 310 stone patients in whom 24-hour
      urine chemistry was examined on regular diets on 2 or more occasions during
      follow-up. Totally, 1361 specimens were analyzed in them. RESULTS: In the male
      subjects, the average urinary citrate excretion was 450.9 +/- 284.4 mg/ day,
      whereas in the female, 536.5 +/- 305.9 mg/day (p < 0.0001). Eventually,
      hypocitraturia was found in 119 of the 310 patients (38.4 %). Of 222 with calcium
      stones, 70 (31.5 %) had hypocitraturia. In 32 of those, potential causes of
      hypocitraturia were identified, but in the rest, no apparent cause was found. In
      the latter, the net gastrointestinal alkali absorption was calculated from the 24
      hour urine chemical data, and it was lower in those with hypocitraturia than in
      the normal control (9.2 vs. 34.4). CONCLUSION: It was suggested that defective
      gastrointestinal alkali absorption may be involved in hypocitraturia of calcium
      stone patients.

PMID- 14714832
TI  - The sharing of target-epitopes between human anti-ABO hemagglutinating and anti
      Pig (xeno) endothelium or anti-Pig thyroglobulin antibodies.
AB  - To select congenial pairs between donor-pig and recipient-human for the future
      xenotransplantation, the levels of xeno-IgM natural antibodies (NAb) were
      analyzed in healthy subjects and hemodialysis patients by ELISA tests, which
      target swine-derived crude endothelial cells (P16N) or proteins (thyroglobulin;
      TG). The total IgM concentration was lower in hemodialysis patients than in
      healthy subjects, but there was no difference in IgM NAb titer between the two
      groups. Individuals with non-B blood types (A, O) exibited significantly higher
      IgM NAb titer compared with those with B blood types (B, AB). A blood type
      individuals showed higher killing activity against P16N than those with B, AB or
      O types with a statistical significance. Sera from A blood type, after being
      absorbed with red blood cells (RBC) from B blood type, decreased their IgM titer
      against TG to the level of sera from B blood type. Meanwhile, sera from A blood
      type significantly decreased hemagglutinin titer against B-RBC after passage
      through a TG-coated affinity column. We conclude that human anti-B-RBC and anti
      Pig xeno NAb have certain common binding epitopes, which might be a branched B
      carbohydrate structure.

PMID- 14714833
TI  - Urolithiasis in geriatric patients.
AB  - OBJECTIVES: We intended to find risk factors for urolitiasis and its recurrence
      in a geriatric population. PATIENTS AND METHODS: The medical records of 209
      elderly stone patients over age 65 were reviewed. They had been regularly seen at
      our stone clinic for a mean follow-up period of 1385 +/- 1324 days after
      urolithiasis was diagnosed. RESULTS: The elderly population comprised 9.6 % of
      all the stone patients followed at the stone clinic. Regarding stone
      compositions, calcium oxalate and calcium phosphate were most common in the
      elderly patients (80 %). The incidence of uric acid stones was higher in the
      elderly patient group than in the younger group (10.7 % vs. 5.1 %; p = 0.0046).
      Recurrent stones were seen in 18 of the 207 geriatric patients (15.4 %) during
      the follow-up period. The urinary calcium excretion of the recurrent stone
      patients was significantly higher than in those without recurrence (293 +/- 138
      mg vs. 177 +/- 98 mg/day, p = 0.0035). However, the probability of stone
      recurrence estimated by Kaplan-Meier curves was as equivalent in the elderly
      patient group as in the younger group. CONCLUSIONS: Hypercalciuria may also play
      a part in stone recurrence of geriatric patients.

PMID- 14714834
TI  - A case for gastrointestinal stromal tumor (GIST) with reference to its
      ultrastructure and 'gain-of-function' mutation.
AB  - A case for primary gastrointestinal stromal tumor (GIST) is described with
      reference to its ultrastructural characteristics and mutation within the exon 11
      of c-kit gene. A forty-seven years old woman complaining of dysphasia was
      examined by endoscopy, which depicted a submucosal tumor (70 mm in diameter) with
      ulcerations at the fundus of the stomach. Histopathologically, the tumor cells
      had large nuclei and eosinophilic cytoplasm and were frequently during mitosis
      phase. The tumor cells were immunopositive for KIT, CD 34 and vimentin,
      suggesting their fibroblast-like characteristics. In contrast, desmin and S-100,
      a smooth muscle and an enteroglial marker, were not immunopositive within the
      cells. At least 30 % of the tumor cells possessed MIB-I and 20 % of them
      possessed p53, which are compatible with fast development of the tumor. By
      electron microscopy, the tumor cells possessed large oval nuclei, abundant
      mitochondria, caveolae and smooth endoplasmic reticulums, while no gap junctions
      were seen on the cells: The tumor cells thus possessed interstitial cells-like
      characteristics at least in part. DNA mutation search for the tumor cells however
      realized no gain-of-function mutation within the exon 11 of the c-kit gene,
      suggesting existence of other mechanism for neoplasmic growth of the tumor cells
      classified as gastrointestinal stromal tumors.

PMID- 14714835
TI  - Clinical evaluation of marginal fit of a new experimental all-ceramic system
      before and after cementation.
AB  - PURPOSE: The purpose of this in vivo study was to evaluate the marginal fit of
      inlay and crown abutments for fixed partial dentures (FPD) made from a new all
      ceramic material. MATERIALS AND METHODS: Sixteen patients were selected for the
      study. After abutment preparation, impressions were made and master dies were
      fabricated. FPDs were made with the experimental heat-pressed lithium-disilicate
      glass-ceramic following the manufacturer's recommendations. At random, one
      abutment of each FPD was chosen for evaluation (11 crown and 8 inlay abutments).
      Impressions of the restoration margins were taken before and after adhesive
      cementation. Replicas of the abutment margins were investigated by SEM. The
      marginal discrepancies were evaluated in sections of 200 microm. The highest
      value of each section was applied, and the mean of all sections of each replica
      was used for statistical analysis. RESULTS: The median of the marginal
      discrepancies before cementation was 96 microm for crowns and 89 microm for
      inlays. After adhesive cementation, the median increased for crowns to 130 microm
      and for inlays to 92 microm, a significant increase in the marginal discrepancies
      caused by cementation for crowns, but not for inlays. There were no significant
      differences between the discrepancies of crowns and inlays before or after
      cementation. CONCLUSION: The maximum marginal discrepancies found in this study
      were between 50 and 265 microm before cementation and between 70 and 285 microm
      after cementation, with no significant differences between the means for crowns
      and inlays. Adhesive cementation caused a significant increase of the marginal
      discrepancies for crown, but not inlay, abutments.

PMID- 14714836
TI  - Clinical behavior of translucent-fiber posts: a 2-year prospective study.
AB  - PURPOSE: This study prospectively evaluated the clinical performance of three
      types of translucent posts over a follow-up period of between 2 and 3 years.
      MATERIALS AND METHODS: Selected were 225 patients with one premolar in need of
      endodontic treatment, followed by restoration with a fiber post and porcelain
      crown. The sample was randomly divided into three groups of 75 patients each. The
      same type of post was used in all patients within a group: group 1 = Aesthetic
      Plus; group 2 = DT; and group 3 = FRC Postec. For bonding the post, a light
      curing adhesive (One-Step) and a dual-curing resin cement (Duo-Link) were applied
      in group 1 and 2 roots, whereas self-curing materials (Excite DSC as adhesive and
      MultiLink as resin cement) were used in group 3. After 6, 12, and 24 months,
      patients were recalled, and a clinical and radiographic examination was
      performed. For some patients, 30-month follow-up data were also collected.
      RESULTS: Debonding of the post occurrred in eight cases (3.5%); in another six
      cases, a recurrence of the periapical lesion was reported. CONCLUSION: The
      statistical analysis did not reveal any significant difference in the survival
      rate of the tested posts, suggesting that all are equally and sufficiently
      reliable for clinical use.

PMID- 14714837
TI  - Cytotoxicity of dental casting alloys after conditioning in distilled water.
AB  - PURPOSE: This study investigated the cytotoxicity of various types of dental
      casting alloys after they had been conditioned in distilled water. MATERIALS AND
      METHODS: The casting alloys investigated included one high-noble alloy
      (Bioherador N) and six base-metal alloys, including four Ni-Cr alloys (Remanium
      CS, Heranium NA, Wiron 99, CB Soft), one Co-Cr alloy (Wirobond C), and one Cu
      based alloy (Thermobond). Ten disks from each alloy were conditioned in distilled
      water at 37 degrees C for either 72 or 168 hours. The cytotoxicity of the alloys
      was then tested on Balb/C 3T3 fibroblasts, which were exposed to the alloys for 3
      days at 37 degrees C. Cell viability was determined by the MTT method. The data
      were analyzed by ANOVA, and follow-up comparison between the groups was carried
      out using Tukey and t tests. RESULTS: ANOVA revealed a significant effect of
      alloy type and conditioning time (P < .001). Bioherador N was significantly less
      toxic than all the other alloys in the 72-hour conditioned group. After 168 hours
      of conditioning, its cytotoxicity was not different (P > .05) from that of
      Remanium CS, Wiron 99, and Wirobond C. Thermobond and CB Soft were significantly
      more toxic than the other alloys at both conditioning times. CONCLUSION:
      Conditioning of base-metal alloys, other than those containing Cu, for 168 hours
      in distilled water makes their cytotoxicity levels comparable to that of the high
      noble alloy.

PMID- 14714838
TI  - Implant treatment in the edentulous mandible: a prospective study on Branemark
      system implants over more than 20 years.
AB  - PURPOSE: This prospective investigation studied the clinical and radiographic
      performance of mandibular fixed prostheses supported by osseointegrated implants
      over more than 20 years. MATERIALS AND METHODS: A total of 273 standard Branemark
      implants (10 mm long) were placed in 47 patients between 1978 and 1982. Clinical
      and radiographic data collected at several examinations over the 20-year
      observation period have been reported previously. This study presents the outcome
      of the latest follow-up after 20 to 23 years. RESULTS: Thirty patients (64%; 75%
      of those still alive) attended the 20-year follow-up examination. Three implants
      were lost during the entire observation period, and the 20-year implant
      cumulative survival rate was 98.9%. All patients had continuous prosthesis
      function, but two had their mandibular prostheses remade during the 20 years. No
      implants or prostheses were lost or fractured during the last 5 years, and only a
      few prosthodontic complications were noted. The mean bone level was 1.6 mm (SD
      0.90) below the reference point after 20 years, and mean bone loss was 0.2 mm (SD
      0.22) between the 15- and 20-year follow-ups. Thirty-seven implants (24%) showed
      more than two exposed threads at the 15-year follow-up examination, but only four
      implants (3%) presented pain and/or bone loss exceeding one thread (0.6 mm)
      during the last 5 years. CONCLUSION: The successful treatment result after 15
      years continued up to more than 20 years in function. During the last 5 years, a
      majority of the implants with several exposed implant threads could be maintained
      without any complications, and the frequency of implants showing signs of ongoing
      peri-implantitis was less than 3%.

PMID- 14714839
TI  - Comparisons of chewing difficulty of consumed foods with mandibular conventional
      dentures and implant-supported overdentures in diabetic denture wearers.
AB  - PURPOSE: This study compared the chewing difficulty of foods in diets of denture
      wearers with mandibular conventional and implant-supported overdentures.
      MATERIALS AND METHODS: One-week dietary logs were evaluated for 58 subjects with
      controlled diabetes at baseline with their original dentures and with new
      dentures 6 months after treatment completion. Subjects received new maxillary and
      mandibular complete dentures, 21 with mandibular conventional dentures and 37
      with implant-supported overdentures. A 10-point chewing difficulty rating scale
      (10 for most difficult-to-chew foods) was used to rate food items in the dietary
      logs. RESULTS: ANOVA showed no differences between the chewing difficulty mean
      scores for all foods consumed either at baseline or posttreatment for the two
      groups. However, the mean scores for the combined consumption frequency of
      difficult-to-chew foods (6 to 10) showed a significant decrease following
      treatment with both types of dentures. This decline did not differ significantly
      between the denture types. With original dentures, more than 91% of subjects
      consumed foods with chewing difficulty scores of 6 to 10 at least seven times per
      week. With study dentures, only 21% maintained this level of consumption, with
      the frequency decreasing to four to six times per week in 24% and one to three
      times per week in 43% of subjects. The declines in consumption frequency of more
      difficult to chew foods with study dentures were in a higher percentage of
      subjects in the implant than in the conventional group. CONCLUSION: After 7
      months of adaptation to new dentures, patients consumed fewer difficult-to-chew
      foods than with their original dentures. This decline was more frequent with
      mandibular implant-supported overdentures than with conventional dentures.
      Dietary counseling should be considered as part of implant and complete denture
      therapy.

PMID- 14714840
TI  - Effectiveness of microwave sterilization on three hard chairside reline resins.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of microwave
      irradiation sterilization on hard chairside reline resins. MATERIALS AND METHODS:
      Specimens of three reline resins (Kooliner, Tokuso Rebase, and Ufi Gel Hard) were
      fabricated and subjected to ethylene oxide sterilization. The specimens were then
      individually inoculated (10(7) cfu/mL) with Tryptic Soy Broth media containing
      one of the tested microorganisms (C albicans, S aureus, B subtilis, and P
      aeruginosa). After 48 hours at 37 degrees C, the samples were vortexed for 1
      minute and allowed to stand for 9 minutes, followed by a short vortex to
      resuspend any organisms present. After inoculation, 40 specimens of each material
      were immersed in 200 mL of water and subjected to microwave irradiation at 650 W
      for 6 minutes. Forty non-irradiated specimens were used as positive controls.
      Replicate specimens (25 microL) of suspension were plated at dilutions of 10(-3)
      to 10(-6) on plates of selective media appropriate for each organism. All plates
      were incubated at 37 degrees C for 48 hours. After incubation, colonies were
      counted, and the data were statistically analyzed by the Kruskal-Wallis test.
      Twelve specimens of each material were prepared for SEM. RESULTS: All immersed
      specimens showed consistent sterilization of all the individual organisms after
      microwave irradiation. SEM examination indicated an alteration in cell morphology
      after microwave irradiation. CONCLUSION: Microwave sterilization for 6 minutes at
      650 W proved to be effective for the sterilization of hard chairside reline
      resins.

PMID- 14714841
TI  - Remakes of Colorlogic and IPS Empress ceramic restorations in general practice.
AB  - PURPOSE: The aim of this article was to study frequencies and distribution of
      remakes of all-ceramic inlays/onlays, veneers, and crowns occurring before and
      after cementation. MATERIALS AND METHODS: A total of 2,069 sintered feldspathic
      ceramic restorations (Colorlogic) and 1,136 pressure-molded ceramic restorations
      (IPS Empress 1 and 2) were produced during the study period by one dental
      laboratory. The laboratory gave an unqualified and unlimited guarantee for their
      ceramic restorations. The outcome variable was reports from the clinicians to the
      dental laboratory about any problems related to the restoration, necessitating
      remake. RESULTS: Problems occurring before cementation occurred in 4.4% of the
      restorations. Veneers were remade more frequently than the other types of
      restorations (6.6%). After cementation, the overall 2-year rate of remakes was
      1%, indicating a survival rate of the ceramic restorations of 99%, with
      inlays/onlays exhibiting the highest (99.8%) and crowns the lowest (98.4%) rates.
      This difference in rates was significant. No significant differences in remakes
      between ceramics or tooth categories were found. CONCLUSION: There were few
      problems in a short- to medium-term perspective that, in the opinion of general
      practitioners, necessitated remakes of all-ceramic restorations.

PMID- 14714842
TI  - Evaluation of custom-made procera ceramic abutments for single-implant tooth
      replacement: a prospective 1-year follow-up study.
AB  - PURPOSE: The aim of this study was to evaluate the clinical performance of
      customized ceramic single-implant abutments in combination with two different
      techniques for fabricating crowns. MATERIALS AND METHODS: Twenty consecutive
      patients were provided with 24 single-implant restorations with customized
      ceramic abutments. The restorations were either cemented to the abutment (n = 13)
      or fabricated with the veneering material fused directly onto the ceramic
      abutment (n = 11). The patients were evaluated at 6 and 12 months with
      radiographs and clinical parameters for complications and soft tissue response.
      RESULTS: All implants and restorations were still in function after 1 year. Few
      clinical problems were reported during the follow-up period. The interproximal
      soft tissue recovered to near normal size. The mean marginal bone loss was
      similar for both groups, reaching an average of 0.3 mm (SD 0.71) after 1 year in
      function. CONCLUSION: The short-term results indicate that customized ceramic
      abutments are successful and have comparable function, regardless of fabrication
      method.

PMID- 14714843
TI  - A 5-year follow-up of signs and symptoms of TMD and radiographic findings in the
      elderly.
AB  - PURPOSE: The aim was to clarify the associations among subjective symptoms,
      clinical signs of temporomandibular disorders (TMD), and radiographic findings in
      the mandibular condyles of elderly people during a 5-year follow-up. MATERIALS
      AND METHODS: As part of a comprehensive medical survey of a random sample born in
      1904, 1909, and 1914 (Helsinki Aging Study), 364 subjects living in Helsinki
      participated in the dental part of the examination during 1990 and 1991; after 5
      years, 103 of these were reexamined. Comprehensive data on TMD were available for
      94 subjects, and radiographic data were available for 88. TMD were assessed by
      Helkimo's anamnestic and clinical indices, and radiographic status was assessed
      by panoramic radiographs. RESULTS: During the 5-year follow-up, reported
      anamnestic symptoms of TMD for men changed little (9%); among women, the change
      from baseline was 42%. When the unchanged indices were compared, the gender
      difference was obvious. At baseline, 5% of the women, but no men, had severe
      signs (clinical index III) of TMD. At the end of follow-up, none showed severe
      signs. Comparison of radiographic findings between baseline and follow-up showed
      no differences, nor did differences appear in associations between radiographic
      findings and anamnestic or clinical indices. CONCLUSION: During the 5-year follow
      up, signs and symptoms of TMD in these elderly individuals became milder or
      vanished. The radiographic status of the condyles remained stable, and no
      association appeared between radiographic findings and signs and symptoms of TMD.

PMID- 14714844
TI  - Bonding indirect resin composites to metal: Part 1. Comparison of shear bond
      strengths between different metal-resin bonding systems and a metal-ceramic
      system.
AB  - PURPOSE: This laboratory study compared the shear bond strength between three
      indirect resin composites and a noble alloy using their respective bonding
      systems. MATERIALS AND METHODS: One hundred twenty disks cast in a medium-gold,
      high-noble metal-ceramic alloy (V-Deltaloy) were divided equally into four groups
      and received different treatments for veneering: Conventional feldspathic
      porcelain (Omega) was applied on one set of specimens to be used as a control,
      and three indirect resin composites (Artglass, Sculpture, Targis) with their
      respective bonding systems were used for the other groups. The specimens were
      tested in a parallel shear test, half of them after 24-hour dry storage at room
      temperature and the rest after 10-day storage in normal saline solution at 37
      degrees C and thermocycling. The fractured specimens were evaluated to determine
      the nature of the failure. RESULTS: The mean shear bond strength values (in MPa),
      before and after wet storage and thermocycling, were 30 and 23 for the metal
      ceramic group, 29 and 23 for the Artglass group, 20 and 19 for the Sculpture
      group, and 17 and 14 for the Targis group, respectively. The metal-ceramic and
      Artglass groups exhibited significantly higher bond strengths than the other two
      groups. All specimens, with the exception of the Sculpture group, showed a
      significant decrease in bond strength after wet storage and thermocycling.
      CONCLUSION: No group exceeded the shear bond strength of the metal-ceramic group,
      but the Artglass group with its respective metal-resin bonding system exhibited
      similar bond strengths. The Sculpture group showed a stable bond after water
      storage and thermocycling.

PMID- 14714845
TI  - Ceramic implant abutments for short-span FPDs: a prospective 5-year multicenter
      study.
AB  - PURPOSE: A prospective, randomized, controlled 5-year multicenter study evaluated
      the long-term clinical function of CerAdapt ceramic abutments compared to
      titanium abutments on Branemark implants supporting short-span fixed partial
      dentures (FPD). MATERIALS AND METHODS: Initially, 105 Branemark implants were
      placed in a total of 32 patients at three different clinics; 103 implants
      remained after initial healing. Fifty-three ceramic and 50 titanium abutments
      were connected to support 36 FPDs, 19 on ceramic and 17 on titanium abutments.
      RESULTS: Thirty patients with 29 FPDs were examined after 5 years. There was a
      cumulative success rate of 97.2% for FPDs (94.7% for ceramic and 100% for
      titanium abutment-supported FPDs). One of 53 ceramic and none of 50 titanium
      abutments failed, giving survival rates of 98.1% and 100%, respectively. There
      was a mean marginal bone loss of 0.3 mm and 0.4 mm, respectively, for ceramic and
      titanium abutments. Soft tissues around abutments and adjacent teeth appeared
      healthy, and no significant differences were recorded for mucosal bleeding and
      plaque between ceramic and titanium abutments. Crown margins at FPD insertion
      were positioned as follows: 21% submucosally, 33% at the mucosal margin, and 46%
      supramucosally. Changes in mucosal level were recorded at 12% of the abutments,
      with 73% of all changes recorded at ceramic abutments. There was a balance
      between more or less exposed crown margins during the first 2 years, in contrast
      to the 2- to 5-year period, when all changes meant less exposed margins.
      CONCLUSION: Safe long-term functional and esthetic results can be achieved with
      CerAdapt alumina ceramic abutments on Branemark implants for short-span FPDs.

PMID- 14714846
TI  - Effects of local cooling rate and processing variables on leucite in dental
      porcelain.
AB  - PURPOSE: This research determined whether there is a measurable effect of local
      geometry factors on leucite content of dental porcelain in fixed partial dentures
      (FPD). MATERIALS AND METHODS: Four-unit FPD frameworks (n = 36) were fabricated
      using a nickel-chromium alloy (Rexillium III). Body porcelain (Crystar, shade A2)
      was applied in one increment and subjected to two simulated body firings,
      followed by a simulated glaze firing to achieve a thickness of 1.5 to 2.0 mm. The
      completed FPD specimens were randomly assigned to three groups of 12 specimens
      each: (1) simulated post-soldering, (2) multiple firing, and (3) control. The
      FPDs from each test group were sectioned into individual units: canine retainer,
      premolar pontic, molar pontic, and molar retainer. The porcelain was removed from
      each unit, and the leucite content was measured via quantitative x-ray
      diffraction. RESULTS: Porcelain cracking indicated that the soldering simulation
      had successfully reproduced conditions in the dental laboratory that result in
      porcelain cracking during soldering. The leucite content was not significantly
      different between the retainer and pontic units for either the soldering
      simulation or control FPDs, although the canine retainer units did have a
      slightly lower leucite content than the pooled values of the other units.
      Comparison of the pooled data for the three groups indicated statistically
      significant differences among the leucite contents. CONCLUSION: Compared to the
      control, the simulated post-soldering procedure produced a significant increase
      in leucite, and the multiple firing group exhibited a significant decrease in
      leucite. Increases in leucite weight fraction during post-soldering operations
      and the larger thermally induced stresses that accompany these leucite increases
      are responsible for the cracking that occurs.

PMID- 14714847
TI  - Fracture load of CAD/CAM-generated slot-inlay FPDs.
AB  - PURPOSE: This study investigated fracture load of computer-aided
      design/manufacturing (CAD/CAM)-generated slot-inlay fixed partial dentures (FPD)
      machined from ceramic and composite. MATERIALS AND METHODS: Ninety slot-inlay
      FPDs were machined in groups of 15 specimens each using the same design on a
      Cerec 3 unit. Materials were assigned to groups: (1) Mk II feldspathic ceramic,
      (2) ProCAD glass-ceramic, (3) glass-ceramic 1, (4) glass-ceramic 2, (5) composite
      1, and (6) composite 2. The slot-inlay FPDs were placed on models with two
      abutment teeth without cementation and loaded to fracture. For control, test bars
      (n = 15) were machined from each of the materials, and flexural strength was
      examined using three-point bending. Data were statistically analyzed using ANOVA
      and Scheffe tests. RESULTS: Fracture load of groups 4 (1,557 N, SD 236), 5 (1,048
      N, SD 77), and 6 (1,512 N, SD 106) was significantly higher than that of groups 1
      (652 N, SD 53) and 2 (773 N, SD 65). Flexural strength of group 4 (256 MPa, SD
      20) was significantly higher than that of groups 1 (103 MPa, SD 6), 2 (127 MPa,
      SD 15), 3 (162 MPa, SD 32), 5 (178 MPa, SD 18), and 6 (170 MPa, SD 20).
      CONCLUSION: Fracture loads of glass-ceramic 2 and composite 2 appear adequate for
      CAD/CAM slot-inlay FPDs.

PMID- 14714848
TI  - Mandibular bone mineral density changes in complete and removable partial denture
      wearers: a 6-month follow-up study.
AB  - PURPOSE: The purpose of the study was to determine the changes in bone mineral
      density of the mandible in complete and removable free-end saddle denture wearers
      over a 6-month period. MATERIALS AND METHODS: Twenty removable partial denture
      patients and 20 complete denture wearers participated. Two dental panoramic
      radiographs were taken from each patient, the first prior to denture delivery and
      the second after 6 months of denture wearing. Bone mineral density measurements
      were performed on panoramic radiographs with a five-step copper stepwedge
      attached to each film cassette. Bone mineral density values of the measured
      regions of interest were expressed in equivalents of the stepwedge thickness
      (mm). RESULTS: The results revealed minor changes in bone mineral density values
      of the examined regions in the 6-month period. Under the distal end of complete
      denture saddles, the bone mineral density values decreased, whereas the values
      under the distal end of removable partial dentures increased. However, the
      difference between the first and second measurements was not significant. In each
      of the examined groups, the bone mineral density values at the gonion increased
      significantly by approximately 20%. This was attributed to the increased strain
      forces of the masseter muscle at the gonion after denture delivery. CONCLUSION:
      Significant increase of bone mineral density values was registered 2 mm above the
      gonion in both complete and removable partial denture wearers. Age and gender
      were not related to the bone mineral density changes over a 6-month period.

PMID- 14714849
TI  - A semi-micromethod for determination of oxalate in human plasma.
AB  - An enzymatic semi-micromethod for oxalate determination in human plasma was
      elaborated. The principle of the method depends on the oxalate isolation from
      deproteinized plasma, following determination by the calorimetric oxalate oxidase
      peroxidase-indamine system. This method protects against internal oxalate losses
      and excludes an interference of contaminations. Results, obtained by this method,
      were reliable and ideally suited for use as real normal values (less than or
      equal to 6 microM) of oxalate content in the plasma of healthy individuals. The
      elaborated method, which can assay plasma oxalate accurately in normal
      individuals as well as in hyperoxalemic conditions is superior to those
      previously used. The procedure of semi-micromethod does not require expensive
      equipments and apparatus: it is simple and easy to perform in every laboratory
      and takes little time.

PMID- 14714851
TI  - Hydrolysis of N,N- and N,S-dimethyl derivatives of 2-thiophenobarbital.
AB  - Kinetics of hydrolysis of N,N- and N,S-dimethyl-2-thiophenobarbital and products
      of this reaction were investigated. The UV spectroscopy served as a tool for
      kinetic investigations and chromatography was used to separate and isolate the
      main products of hydrolysis. These products were identified by spectroscopic
      methods and the course of hydrolysis of both isomers was compared.

PMID- 14714850
TI  - Hydrolysis of N- and S-monomethyl derivatives of 2-thiophenobarbital.
AB  - Kinetics of hydrolysis of S-methyl-2-thiophenobarbital in aqueous solutions was
      investigated using the UV spectroscopic method within the pH range 1.5-12.9 at 60
      degrees C. Chromatography was used to separate and isolate the products of
      hydrolysis of this compound and its N-methyl isomer. The products were identified
      by spectroscopic methods and the course of hydrolysis of both isomers were
      compared.

PMID- 14714852
TI  - Interaction of thioridazine with ocular melanin in vitro.
AB  - The aim of this study was to examine in vitro the binding capacity of
      thioridazine to natural melanin isolated from pig eyes and to synthetic DOPA
      melanin. The amount of drug bound to melanin was determined by the use of the UV
      spectrophotometric method. Studies on the kinetics of thioridazine-melanin
      complex formation showed that the amount of drug bound to melanin increases with
      increasing initial drug concentration and the prolongation or incubation time,
      allowed to attain equilibrium state after about 24 hours. Binding parameters,
      i.e., the number of independent binding sites and the association constants were
      determined on the basis of Scatchard plots. For thioridazine-ocular melanin and
      thioridazine-DOPA-melanin complexes two classes of binding sites were found with
      the association constants K1 approximately 2 x 10(4) M(-1) and K2 approximately 9
      x 10(2) M(-1). For ocular and synthetic melanin complexes with thioridazine no
      significant differences in the values of binding parameters were found. The
      demonstrated ability of thioridazine to interact with melanin in vitro is
      discussed in relation to this drug ocular toxicity in vivo.

PMID- 14714853
TI  - Alteration of growth and metabolic activity of cells in the presence of
      propranolol and metoprolol.
AB  - Mechanisms of action at the cellular level of a variety of drugs and xenobiotics
      may be assessed using Chlorella vulgaris cells. Synchronous culture, which
      consists of cells at the same phase of development, provides the most convenient
      model for studying processes at the cellular level. Stability of metabolic
      activity of synchronously growing cells is achieved by conducting cell culturing
      under strictly controlled conditions. The aim of the present study was to
      determine to what extent propranolol and metoprolol alter the Chlorella vulgaris
      metabolic activity, expressed by the number of progeny cells, the culture
      absorbance at lambda = 680 nm and the amount of selected photosynthetic pigments
      (chlorophyll a, chlorophyll b, antheraxanthin, lutein, violaxanthin and beta
      carotene). Three different concentrations (10(-4), 10(-5) and 10(-6) M) of
      propranolol and metoprolol were administered to the Chlorella vulgaris cultures.
      It has been demonstrated that the higher the propranolol and metoprolol
      concentrations (from 10(-6) M to 10(-4) M) the lower the number of progeny cells
      in the cultures, expressed by the lower values of division coefficient. Both the
      propranolol and metoprolol caused a decrease in the photosynthetic pigments
      production in the mother cells. This effect was more important in the propranolol
      treated cultures. The higher values of photosynthetic pigments concentrations in
      the progeny cells grown under the presence of a drug indicate that both the drugs
      tested influence mainly the cell growth and in a lower manner--their metabolic
      activity, expressed by the production of photosynthetic pigments.

PMID- 14714854
TI  - Comparative kinetics of azathioprine and metazathioprine mercaptolysis in
      presence of physiological thiols.
AB  - Kinetic parameters of mercaptolysis of azathioprine (AZA) and metazathioprine
      (MAZA) to 6-mercaptopurine in phosphate buffer, pH 7.4, under the influence of
      physiological thiols (glutathione and cysteine) at 25 degrees, 30 degrees and 37
      degrees C were determined and compared. It comes out that the mercaptolysis of
      MAZA is significantly faster under the influence of both mentioned thiols if
      compared to that reaction of AZA. Furthermore, the mercaptolysis of MAZA and AZA
      proceeded significantly faster under the influence of cysteine than on the
      glutathione heterolysis.

PMID- 14714855
TI  - Search for substances with antioxidant and antiamnestic activities among 2
      substituted 4-(3H)-quinazolones.
AB  - We have synthesised some of 2-substituted 4-(3H)-quinazolones by the reaction
      with benzaldehyde and cinnamic aldehyde and their derivatives. It is shown that
      the intensity of the reaction depends on electrophilic properties of carbonyl
      compounds and steric factors. The elemental analysis, ultraviolet (UV), infrared
      (IR) and nuclear magnetic resonance (NMR) spectroscopy confirmed the structure of
      synthesised compounds, their individuality being checked by thin-layer
      chromatography. The results of biological experiments show that the synthesised 2
      substituted 4-(3H)-quinazolones have an expressed antioxidant and antiamnestic
      activity and are prospective for further research of their nootropic activity.

PMID- 14714856
TI  - A synthesis of 3alpha,6alpha,17alpha-trihydroxy-5beta-pregnan-20-one (triolone)
      from 3alpha,6alpha-dihydroxy-5beta-pregnan-20-one (diolone).
AB  - An optimization of synthesis of 3alpha,6alpha,17alpha-trihydroxy-5beta-pregnan-20
      one from 3alpha,6alpha-dihydroxy-5beta-pregnan-20-one by subsequent
      acetylenolization, epoxidation, and ring opening reactions has been described.
      Epoxide hydrolysis at different temperatures (room and at boiling) has also been
      investigated.

PMID- 14714857
TI  - Synthesis and evaluation of substituted naphthalimide nitrogen mustards as
      rationally designed anticancer compounds.
AB  - Bromonapmustine 4a and chloronapmustine 4b, two new nitrogen mustards of
      substituted naphthalimides, have been synthesized as mixed-function anticancer
      compounds from 4-bromo- and 4-chloro-N-(2-hydroxyethyl)-naphthalimide
      respectively following a three-step process. Their chemical alkylating activity
      exceeded that of nor-HN2. Their antitumour efficacy were assessed in vivo in two
      murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S
      180) by measuring the increase in median survival times (MST) of drug treated (T)
      over untreated control (C) mice. Two standard clinical drugs, namely endoxan
      (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for
      comparison. Both of them have displayed substantial and reproducible antitumoural
      activity in these tumours comparable with 5-FU. These compounds inhibit the
      synthesis of DNA and RNA in S-180 tumour cells. These were further screened in
      vitro in 3 different human tumour cell lines but no significant activity was
      observed in those lines.

PMID- 14714858
TI  - Synthesis and antiproliferative activity in vitro of new 3-substituted
      aminoisoxazolo[5,4-b]pyridines.
AB  - The synthesis of 3-aminoisoxazolo[5,4-b]pyridine [III] and of several new 3
      substituted aminoisoxazolo[5,4-b]pyridines is described. 3-Aminoisoxazlo[5,4
      b]pyridine [III] was subjected to reactions with the acid halides and substituted
      aromatic aldehydes, leading to the production of the corresponding amides IV-VII,
      IX, XI-XVI and new tricyclic pyridoisoxazolopyrimidine VIII and Schiff bases XX
      XXIV. 4-Chlorobutyroamide IX cyclized into 3-(pyrrolidinon-1-yl)isoxazolo[5,4
      b]pyridine [X]. 3-Chloroacetylaminoisoxaxolo[5,4-b]pyridine [V] in reaction with
      secondary amines gave 3-aminoacetylaminoisoxazolo[5,4-b]pyridines XVII-XIX. The
      structures of the products II-XXIV were established on the basis of elemental
      analysis and spectral data IR, 1H NMR and MS. Selected compounds were tested for
      their antiproliferative activity in vitro. Two of them: 3-chloroacetyl-[V] and 3
      2-bromo-propionylaminoisoxazolo[5,4-b]pyridine [VI] revealed cytotoxic activity
      against the cells of 8 various human or mouse tumor cell lines applied. Their
      ID50 (inhibitory dose 50%) values are in the range of the international activity
      criterion for synthetic agents (4 microg/ml).

PMID- 14714859
TI  - Improving the O/W emusifying properties of rapeseed lecithin ethanol insoluble
      fraction by acetylation.
AB  - The effect of acetylation of rapeseed lecithin ethanol insoluble fraction (LEIF)
      containing 25% phosphatidylethanolamine (PE) on the O/W emulsifying properties
      was reported. In the study, acetic anhydride (50-150 mmol/100 g) and pyridine (0
      30 mmole/100 g) were used. The PE conversion to N-acetyl-PE in LEIF determined by
      the HPLC method was varied from 18.2 to 84.7% and depended essentially on the
      acetylating agent amount and pyridine quantity used in acetylation. Emulsions of
      the O/W systems containing lecithin emulsifiers with different PE conversion
      degree were prepared and evaluated for its stability. It was found that the
      acetylation of LEIF improves its emulsifying properties and in the formation of
      emulsions containing soya oil, provided a decrease in oil droplet size and
      polydispersity index.

PMID- 14714860
TI  - Qualitative and quantitative chromatographic investigation of hydroquinone
      derivatives in Pyrus communis L. flowers.
AB  - The qualitative analysis and quantitative determination of hydroquinone
      derivatives (arbutin, pyroside) in the flowers of naturally growing pear tree and
      of its four cultivated varieties (Pomaranczowka, Lukasowka, Klapsa, Salisbury)
      were carried out. The comparative qualitative analysis of hydroquinone
      derivatives was investigated chromatographically (TLC). Arbutin and pyroside were
      found in all the studied plant materials and free hydroquinone was found in buds
      of naturally growing pear. The content of arbutin and pyroside was determined by
      the HPLC method.

PMID- 14714861
TI  - Kaempferol and quercetin glycosides from Rubus idaeus L. leaves.
AB  - Quercetin 3-0-beta-D-glucoside (I), quercetin and kaempferol 3-0-beta-D
      galactosides (II, III), kaempferol 3-0-beta-L-arabinopyranoside (IV), kaempferol
      3-0-beta-D-(6''-E-p-coumaroyl)-glucoside (tiliroside) (V) and methyl gallate (VI)
      were isolated from Rubus idaeus L. subspecies culture of Norna leaves and fully
      characterized.

PMID- 14714862
TI  - Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa
      Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and
      hepatorenal functions in mice.
AB  - Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%)
      and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and
      cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75
      mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and
      hematological parameters in mice were studied. No significant alteration of RBC
      count and hemoglobin content was observed in all dose level of treatment in MECR
      and MECO treated mice whereas significant increase of clotting time was seen in
      moderate and high doses in both case. MECR and MECO both caused significant
      increase in WBC count only in high dose level of treatment. Both the extracts in
      medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol
      significantly. Serum alkaline phosphatase and total bilirubin were also increased
      by both moderate and high dose level of treatments in MECR and MECO treated mice
      respectively. Low dose of both the extract did not exhibit any significant change
      of creatinine and serum protein level. But high dose level of MECR and MECO
      significantly increased creatinine level. Increase in plasma cholesterol may be
      due to decrease in cholesterol catabolism owing to liver dysfunction of due to
      the intake of MECO itself as it was found to be steroid in nature. Elevated level
      of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose
      level of weekly treated mice may be due to improper liver function following the
      treatment. Increased urea, non protein nitrogen and creatinine content in blood
      have been observed with impaired renal function. The slightly higher toxicity in
      case of MECO treated mice may be due to the presence of cardenolide glycosides in
      the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15
      mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and
      kidney functions and hematological parameters.

PMID- 14714863
TI  - Rhizoremediation: a beneficial plant-microbe interaction.
AB  - Worldwide, contamination of soil and ground water is a severe problem. The
      negative effects of pollutants on the environment and on human health are diverse
      and depend on the nature of the pollution. The search for alternative methods for
      excavation and incineration to clean polluted sites resulted in the application
      of bioremediation techniques. In this review, we describe some generally accepted
      bioremediation tools and subsequently focus on the combination of two approaches,
      phytoremediation and bioaugmentation, resulting in rhizoremediation. During
      rhizoremediation, exudates derived from the plant can help to stimulate the
      survival and action of bacteria, which subsequently results in a more efficient
      degradation of pollutants. The root system of plants can help to spread bacteria
      through soil and help to penetrate otherwise impermeable soil layers. The
      inoculation of pollutant-degrading bacteria on plant seed can be an important
      additive to improve the efficiency of phytoremediation or bioaugmentation.

PMID- 14714864
TI  - Expression of MsLEC1 transgenes in alfalfa plants causes symbiotic abnormalities.
AB  - Legume lectins have been proposed to have important symbiotic roles during
      Rhizobium-legume symbioses. To test this hypothesis, the symbiotic responses of
      transgenic alfalfa plants that express a portion of the putative alfalfa lectin
      gene MsLEC1 or MsLEC2 in either the antisense or sense orientation were analyzed
      following inoculation with wild-type Sinorhizobium meliloti 1021. MsLEC1
      antisense (LEC1AS) plants were stunted, exhibited hypernodulation, and developed
      not only abnormally large nodules but also numerous small nodules, both of which
      senesced prematurely. MsLEC2-antisense plants were intermediate in growth and
      nodule number compared with LEC1AS and vector control plants. The symbiotic
      abnormalities of MsLEC1-sense transgene plants were similar to but milder than
      the responses shown by the LEC1AS plants, whereas MsLEC2-sense transgene plants
      exhibited symbiotic responses that were identical to those of vector and
      nontransgenic control plants. MsLEC1 mRNA accumulation was not detected in nodule
      RNA by Northern blot analysis but was localized to alfalfa nodule meristems and
      the adjacent cells of the invasion zone by in situ hybridization; transcripts
      were also detected in root meristems. A similar spatial pattern of MsLEC2
      expression was found by using a whole-mount in situ hybridization procedure.
      Moreover, mRNAs for an orthologous lectin gene (MaLEC) were detected in white
      sweetclover (Melilotus alba) nodules and root tips.

PMID- 14714865
TI  - Host responses to transient expression of individual genes encoded by Tomato leaf
      curl virus.
AB  - The six open reading frames of Tomato leaf curl virus (TLCV) were expressed in
      host Nicotiana species using a Tobacco mosaic virus vector. Each of the genes,
      except that encoding the viral coat protein, produced a phenotypic effect when
      expressed in planta, but the corresponding untranslatable mutant genes were
      asymptomatic. The C1 (Rep) gene invoked a hypersensitive response in Nicotiana
      clevelandii that restricted the viral construct to sites of infection. Expression
      of the C2 gene in N. benthamiana produced necrotic lesions on inoculated leaves
      as well as severe veinal necrosis on systemically infected leaves. This gene was
      also able to suppress post-transcriptional gene silencing in N. tabacum. C4
      induced viruslike symptoms in host plants tested, providing further evidence for
      the involvement of this gene in symptom expression. Expression of the V1 and C3
      genes caused severe stunting of N. benthamiana plants, indicating they may also
      have a role in symptom development. These results reveal that a complex set of
      interactions between the TLCV gene products and host factors occurs in planta,
      and these are discussed in relation to our current understanding of TLCV gene
      function.

PMID- 14714866
TI  - NPR1-independent activation of immediate early salicylic acid-responsive genes in
      Arabidopsis.
AB  - Salicylic acid (SA) is a key signal for the activation of defense genes in
      response to stress. The activation of late defense genes by SA, such as PR-1,
      involves the participation of the NPR1 protein. This protein acts as coactivator
      of the TGA factors that recognize as-1-like elements in the PR-1 promoter.
      Considering that functional as-1-like elements are also found in the promoter of
      SA- and auxin-responsive immediate early genes, we tested the hypothesis that
      NPR1 is also required for activation of these genes. The expression of the
      immediate early genes glutathione S-transferase (GST6) and glucosyltransferase
      (EIGT) was studied in npr1 mutant and wild-type Arabidopsis plants. In the npr1
      mutant background, SA and 2,4-dichlorophenoxyacetic acid were unable to promote
      transcription of PR-1 but effectively stimulated the expression of GST6 and EIGT.
      Furthermore, increased binding of proteins to the GST6 as-1-like promoter element
      was detected in nuclear extracts from npr1 and wild-type plants after treatment
      with SA. In summary, these results indicate that activation of immediate early
      genes by SA proceeds through an NPR1-independent pathway. Therefore, we propose
      that activation by SA of immediate early and late genes occur by different
      mechanisms.

PMID- 14714868
TI  - Rme1 is necessary for Mi-1-mediated resistance and acts early in the resistance
      pathway.
AB  - The tomato gene Mi-1 confers resistance to root-knot nematodes (Meloidogyne
      spp.), potato aphid, and whitefly. Using genetic screens, we have isolated a
      mutant, rme1 (resistance to Meloidogyne spp.), compromised in resistance to M.
      javanica and potato aphid. Here, we show that the rme1 mutant is also compromised
      in resistance to M. incognita, M. arenaria, and whitefly. In addition, using an
      Agrobacterium-mediated transient assay in leaves to express constitutive gain-of
      function mutant Pto(L205D), we demonstrated that the rme1 mutation is not
      compromised in Pto-mediated hypersensitive response. Moreover, the mutation in
      rme1 does not result in increased virulence of pathogenic Pseudomonas syringae or
      Mi-1-virulent M. incognita. Using a chimeric Mi-1 construct, Mi-DS4, which
      confers constitutive cell death phenotype and A. rhizogenes root transformation,
      we showed that the Mi-1-mediated cell death pathway is intact in this mutant. Our
      results indicate that Rme1 is required for Mi-1-mediated resistance and acts
      either at the same step in the signal transduction pathway as Mi-1 or upstream of
      Mi-1.

PMID- 14714867
TI  - The phytoalexin-inducible multidrug efflux pump AcrAB contributes to virulence in
      the fire blight pathogen, Erwinia amylovora.
AB  - The enterobacterium Erwinia amylovora causes fire blight on members of the family
      Rosaceae, with economic importance on apple and pear. During pathogenesis, the
      bacterium is exposed to a variety of plant-borne antimicrobial compounds. In
      plants of Rosaceae, many constitutively synthesized isoflavonoids affecting
      microorganisms were identified. Bacterial multidrug efflux transporters which
      mediate resistance toward structurally unrelated compounds might confer tolerance
      to these phytoalexins. To prove this hypothesis, we cloned the acrAB locus from
      E. amylovora encoding a resistance nodulation division-type transport system. In
      Escherichia coli, AcrAB of E. amylovora conferred resistance to hydrophobic and
      amphiphilic toxins. An acrB-deficient E. amylovora mutant was impaired in
      virulence on apple rootstock MM 106. Furthermore, it was susceptible toward
      extracts of leaves of MM 106 as well as to the apple phytoalexins phloretin,
      naringenin, quercetin, and (+)-catechin. The expression of acrAB was determined
      using the promoterless reporter gene egfp. The acrAB operon was up-regulated in
      vitro by the addition of phloretin and naringenin. The promoter activity of acrR,
      encoding a regulatory protein involved in acrAB expression, was increased by
      naringenin. In planta, an induction of acrAB was proved by confocal laser
      scanning microscopy. Our results strongly suggest that the AcrAB transport system
      plays an important role as a protein complex required for virulence of E.
      amylovora in resistance toward apple phytoalexins and that it is required for
      successful colonization of a host plant.

PMID- 14714869
TI  - The promoter of the Vicia faba L. leghemoglobin gene VfLb29 is specifically
      activated in the infected cells of root nodules and in the arbuscule-containing
      cells of mycorrhizal roots from different legume and nonlegume plants.
AB  - The VfLb29 leghemoglobin gene promoter was polymerase chain reaction-amplified
      from a Vicia faba genomic library and was fused to the gusAint coding region.
      Expression of the chimeric gene was analyzed in transgenic hairy roots of the
      legumes V. faba, V. hirsuta, and Medicago truncatula as well as in transgenic
      Nicotiana tabacum plants. The VfLb29 promoter was found to be specifically active
      not only in the infected cells of the nitrogen-fixing zone of root nodules but
      also in arbuscule-containing cells of transgenic V. faba and M. truncatula roots
      colonized by the endomycorrhizal fungus Glomus intraradices. In addition to these
      two legumes, specific expression in arbuscule-containing cells was also observed
      in the nonlegume N. tabacum. All studies were done in comparison to the V. faba
      leghemoglobin gene promoter VfLb3 that as VfLb29 was expressed in the infected
      cells of root nodules but showed no activity in endomycorrhiza. An activation of
      the VfLb29 promoter due to hypoxia in metabolically active tissues was excluded.
      The conserved activation in arbuscule-containing cells of legumes and the
      nonlegume N. tabacum suggests a conserved trigger for this promoter in legume and
      nonlegume endomycorrhiza symbioses.

PMID- 14714870
TI  - Early induction of the Arabidopsis GSTF8 promoter by specific strains of the
      fungal pathogen Rhizoctonia solani.
AB  - The Arabidopsis glutathione S-transferase GSTF8 promoter directs root-specific
      responses to stress. In this study, the response of this promoter to plant
      infection with Rhizoctonia solani was investigated using a luciferase reporter
      system. Arabidopsis seedlings harboring the GSTF8:luciferase construct were
      monitored in vivo for bioluminescence following infection with R. solani.
      Although the reporter gene was induced in infected roots, the response differed
      markedly between R. solani strains and was not observed with aggressive strains
      that caused death of the seedlings. The three strains tested in detail progressed
      through typical stages of infection, but ZG1-1 induced the GSTF8 promoter in most
      seedlings, ZG3 induced it in approximately 25% of seedlings, and ZG5 caused
      little response. Induction of specific root segments occurred early in the
      infection process in root regions with very limited mycelium visible. In root
      segments with substantial mycelium, GSTF8 promoter activity no longer was
      observed. Induction by ZG1-1 also was observed in plants harboring a tetramer of
      the ocs element from the GSTF8 promoter, suggesting that this element helps
      mediate the response. Crossing GSTF8:luciferase plants with plants harboring an
      Nah-G construct that degrades salicylic acid did not abolish the response,
      indicating that the GSTF8 promoter response to R. solani may be mediated by
      signals other than salicylic acid.

PMID- 14714871
TI  - Analysis of the involvement of hydroxyanthranilate hydroxycinnamoyltransferase
      and caffeoyl-CoA 3-O-methyltransferase in phytoalexin biosynthesis in oat.
AB  - Two oat genes encoding hydroxycinnamoyl-CoA:hydroxyanthranilate N
      hydroxycinnamoyltransferase (HHT) and S-adenosyl-L-methionine:trans-caffeoyl-CoA
      3-O-methyltransferase (CCoAOMT), both of which are possibly involved in the
      biosynthesis of oat avenanthramide phytoalexins, were cloned and their expression
      profiles in response to biological stress were studied. Four distinct cDNAs of
      oat HHT (AsHHT1-4) were isolated with the degenerative polymerase chain reaction
      method. The enzymatic activity of AsHHT1 expressed in E. coli was found using
      hydroxyanthranilate and hydroxycinnamoyl-CoAs as cosubstrates. Cloned oat CCoAOMT
      (AsCCoAOMT) encoded a polypeptide of 130 amino acid residues with 77.7 to 80.8%
      identities to the CCoAOMT sequences from other plant species. The accumulation of
      AsHHT1 and AsCCoAOMT transcripts increased concomitantly with phytoalexin
      accumulation by the treatment of victorin, a specific elicitor in oat lines
      carrying the Pc-2/Vb gene. Pharmacological approaches indicated the involvement
      of Ca2+, NO, and protein kinases in the signaling pathways of AsHHT1 and
      AsCCoAOMT mRNA induction. When oat leaves were inoculated with Puccinia coronata,
      the mRNA expression of AsHHT1 and AsCCOAOMT increased in both incompatible and
      compatible interactions but more rapidly in incompatible interaction.
      Interestingly, however, significant phytoalexin accumulation was observed only in
      incompatible interaction during the experimental period, suggesting that
      phytoalexin accumulation may be inhibited in one or more posttranscriptional
      processes in the compatible interaction.

PMID- 14714872
TI  - Functional analysis of genes involved in the synthesis of syringolin A by
      Pseudomonas syringae pv. syringae B301 D-R.
AB  - Strains of the phytopathogenic bacterium Pseudomonas syringae pv. syringae
      secrete a family of structurally closely related peptide derivatives dubbed
      syringolins, of which syringolin A is the major variant. The function of
      syringolins in the interaction of P. syringae pv. syringae with their host plants
      presently is unknown. It is hypothesized that they may constitute virulence
      factors. However, syringolins are determinants recognized and reacted to by
      nonhost plant species, and syringolin A has been shown to induce hypersensitive
      death of cells colonized by powdery mildew in wheat and, thus, to reprogram a
      compatible interaction into an incompatible one. Syringolin A is an unusual
      derivative of a tripeptide that contains a 12-membered ring consisting of the
      amino acids 5-methyl-4-amino-2-hexenoic acid and 3,4-dehydrolysine, two
      nonproteinogenic amino acids. Here we report the cloning, sequencing, and
      analysis of genes involved in the biosynthesis of syringolin A. The genes encode
      proteins consisting of modules typical for nonribosomal peptide synthetases and
      type I polyketide synthetases, as well as proteins likely involved in the
      transcriptional regulation of syringolin A biosynthesis and in syringolin A
      export. The structure and arrangement of the modules lead to the formulation of a
      model explaining the synthesis of the tripeptide, including the formation of the
      two nonproteinogenic amino acids in the ring structure of syringolin A.

PMID- 14714873
TI  - Analysis of mechanisms involved in the Cucumber mosaic virus satellite RNA
      mediated transgenic resistance in tomato plants.
AB  - Transgenic tomato (Lycopersicon esculentum Mill. cv. UC82) plants expressing a
      benign variant of Cucumber mosaic virus satellite RNA (CMV Tfn-satRNA) were
      generated. The transformed plants did not produce symptoms when challenged with a
      satRNA-free strain of CMV (CMV-FL). The same plant lines initially were
      susceptible to necrosis elicited by a CMV strain supporting a necrogenic variant
      of satRNA (CMV-77), but a phenotype of total recovery from the necrosis was
      observed in the newly developing leaves. The features of the observed resistance
      were analyzed and are consistent with two different mechanisms of resistance. In
      transgenic plants inoculated with CMV-FL strain, the symptomless phenotype was
      correlated to the down-regulation of CMV by Tfn-satRNA, amplified from the
      transgene transcripts, as the first resistance mechanism. On the other hand, the
      delayed resistance to CMV-77 in transgenic tomato lines was mediated by a
      degradation process that targets satRNAs in a sequence-specific manner. Evidence
      is provided for a correlation between a reduced accumulation level of transgenic
      messenger Tfn-satRNA, the accumulation of small (approximately 23 nucleotides)
      RNAs with sequence homology to satRNAs, the progressively reduced accumulation of
      77-satRNA in infected tissues, and the transition in infected plants from
      diseased to healthy. Thus, events leading to the degradation of satRNA sequences
      indicate a role for RNA silencing as the second mechanism determining resistance
      of transgenic tomato lines.

PMID- 14714874
TI  - The germinlike protein GLP4 exhibits superoxide dismutase activity and is an
      important component of quantitative resistance in wheat and barley.
AB  - Germinlike proteins (GLP) are encoded in plants by a gene family with proposed
      functions in plant development and defense. Genes of GLP subfamily 4 of barley
      (HvGLP4, formerly referred to as HvOxOLP) and the wheat orthologue TaGLP4
      (formerly referred to as TaGLP2a) were previously found to be expressed in
      pathogen-attacked epidermal tissue of barley and wheat leaves, and the
      corresponding proteins are proposed to accumulate in the apoplast. Here, the role
      of HvGLP4 and TaGLP4 in the defense of barley and wheat against Blumeria graminis
      (DC.) E. O. Speer, the cereal powdery mildew fungus, was examined in an epidermal
      transient expression system and in transgenic Arabidopsis thaliana plants
      overexpressing His-tagged HvGLP4. Leaf extracts of transgenic Arabidopsis
      overexpressing HvGLP4 contained a novel His-tagged protein with superoxide
      dismutase activity and HvGLP4 epitopes. Transient overexpression of TaGLP4 and
      HvGLP4 enhanced resistance against B. graminis in wheat and barley, whereas
      transient silencing by RNA interference reduced basal resistance in both cereals.
      The effect of GLP4 overexpression or silencing was strongly influenced by the
      genotype of the plant. The data suggest that members of GLP subfamily 4 are
      components of quantitative resistance in both barley and wheat, acting together
      with other, as yet unknown, plant components.

PMID- 14714875
TI  - Apoplastic pH signaling in barley leaves attacked by the powdery mildew fungus
      Blumeria graminis f. sp. hordei.
AB  - To investigate apoplastic responses of barley (Hordeum vulgare L.) to the barley
      powdery mildew fungus Blumeria graminis f. sp. hordei, noninvasive microprobe
      techniques were employed. H(+)- and Ca(2+)-selective microprobes were inserted
      into open stomata of barley leaves inoculated with Blumeria graminis f. sp.
      hordei race A6 conidia. Resistance gene-mediated responses of barley genotype
      Ingrid (susceptible parent line) and the near-isogenic resistant Ingrid backcross
      lines (I-mlo5, I-Mla12, and I-Mlg) were continuously monitored from 20 min to 4
      days after inoculation. The main events were categorized as short-term responses
      around 2 h after inoculation (hai), intermediate responses around 8 and 12 hai,
      and long-term responses starting between 21 and 24 hai. Short-term responses were
      rapid transient decreases of apoplastic H(+)- and Ca2+ activities that lasted
      minutes only. Kinetics were similar for all genotypes tested, and thus, these
      short-term responses were attributed as nonspecific first encounters of fungal
      surface material with the host plasma membrane. This is supported by the
      observation that a microinjected chitin oligomer (GlcNAc)8 yielded similar
      apoplastic alkalinization. Intermediate responses are trains of H+ (increase)
      spikes that, being different in susceptible Ingrid and penetration-resistant I
      mlo5 (or I-Mlg), were interpreted as accompanying specific events of papillae
      formation. Long-term events were massive slow and long-lasting alkalinizations up
      to two pH units above control. Since these latter changes were only observed with
      near-isogenic hypersensitive reaction (HR)-mounting genotypes I-Mla12 and I-Mlg
      but not with I-mlo5 or, to a smaller extent, with susceptible Ingrid, both
      lacking significant rates of HR, they were rated as cell death specific. It is
      concluded that apoplastic pH changes are important indicators of host-pathogen
      interactions that correlate with both the different stages of fungal development
      and the different types of host defense response.

PMID- 14714876
TI  - Biological Stain Commission annual meeting June 6-7, 2003 Rochester, New York.

PMID- 14714878
TI  - The use of dyes in modern biomedicine.
AB  - The discovery of the aniline dyes in the 19th century and contemporary
      investigation of their use as biological stains by scientists such as Koch and
      Ehrlich led to the idea of selectivity and formed the basis of modern
      chemotherapy; several of these dyes remain in pharmacopoeias. While the
      development of therapeutics has tended to avoid colored compounds due to unwanted
      coloration, the modern application of photosensitizing dyes, both in the fields
      of cancer therapy and anti-infection, depends on this phenomenon. In addition,
      the fluorescence of some anticancer photosensitizers allows their use as tumor
      localizing agents, which is particularly useful in precancerous conditions. It is
      also fitting that dyes employed in Ehrlich's original studies, such as the
      phenothiazinium dye, methylene blue, are now in clinical use for disinfecting
      donated blood products.

PMID- 14714879
TI  - Effect of the lipophilic/hydrophilic character of cationic triarylmethane dyes on
      their selective phototoxicity toward tumor cells.
AB  - The observation that enhanced mitochondrial transmembrane potential is a
      prevalent tumor cell phenotype has provided the conceptual basis for the
      development of mitochondrial targeting as a novel therapeutic strategy for both
      chemo- and photochemotherapy of neoplastic diseases. Because the plasma
      transmembrane potential is negative on the inner side of the cell and the
      mitochondrial transmembrane potential is negative on the inner side of this
      organelle, extensively conjugated cationic molecules (dyes) displaying
      appropriate structural features are driven electrophoretically through these
      membranes and tend to accumulate inside energized mitochondria. As a result of
      the higher mitochondrial transmembrane potential typical of tumor cells, a number
      of cationic dyes preferentially accrue and are retained for longer periods in the
      mitochondria of these cells compared to normal cells. This differential in both
      drug loading and retention brings about the opportunity to attack and destroy
      tumor cells with a high degree of selectivity. Only a small subset of the
      cationic dyes known to accumulate in energized mitochondria mediate the
      destruction of tumor cells with a high degree of selectivity, and the lack of a
      reliable model to describe the structural determinants of this tumor specificity
      has prevented mitochondrial targeting from becoming a more reliable therapeutic
      strategy. We describe here a systematic study of how the molecular structure of
      closely related cationic triarylmethanes affects the selectivity with which these
      dyes mediate the photochemical destruction of tumor cells. Based on our
      observations of how the lipophilic/hydrophilic character of these dyes affects
      tumor selectivity, we propose a simple model to assist in the design of new drugs
      tailored specifically for imaging and selective destruction of neoplastic tissue
      via mitochondrial targeting.

PMID- 14714880
TI  - Investigation of photosensitizing dyes for pathogen reduction in red cell
      suspensions.
AB  - Despite recent advances in blood safety by careful donor selection and
      implementation of infectious disease testing, transmission of viruses, bacteria
      and parasites by transfusion can still rarely occur. One approach to reduce the
      residual risk from currently tested pathogens and to protect against the
      emergence of new ones is to investigate methods for pathogen inactivation. The
      use of photosensitizing dyes for pathogen inactivation has been studied in both
      red cell and platelet blood components. Optimal properties of sensitizing dyes
      for use in red cell suspensions include selection of dyes that traverse cell and
      viral membranes, bind to nucleic acids, absorb light in the red region of the
      spectrum, inactivate a wide range of pathogens, produce little red cell
      photodamage from dye not bound to nucleic acid and do not hemolyze red cells in
      the dark. Early research at the American Red Cross focused on the use of a class
      of dyes with rigid structures, such as the phenothiazine dyes, beginning with the
      prototypical sensitizer methylene blue. Results revealed that methylene blue
      phototreatment could inactivate extracellular virus, but resulted in undesirable
      defects in the red cell membrane that resulted in enhanced hemolysis that became
      evident during extended refrigerated blood storage. In addition, methylene blue
      phototreatment could neither inactivate intracellular viruses nor appreciably
      inactivate bacteria under conditions of extracellualar viral killing. Attempts to
      improve intracellular viral inactivation led to the investigations of more
      hydrophobic phenothiazines, such as methylene violet or dimethylmethylene blue.
      Although these dyes could inactivate intracellular virus, problems with increased
      red cell membrane damage and hemolysis persisted or increased. Further studies
      using red cell additive storage solutions containing high levels of the
      impermeable ion, citrate, to protect against colloidal osmotic hemolysis as well
      as competitive inhibitors to limit sensitizer binding to red cell membranes
      revealed that photoinduced hemolysis stemmed from dye bound to the red cell
      membrane as well as dye free in solution. Use of red cell additive solutions to
      prevent colloidal-osmotic hemolysis and use of novel flexible dyes that only act
      as sensitizers when bound to their targets are two techniques that currently are
      under investigation for reducing red cell damage. Ultimately, the decision to
      implement a photodynamic method for pathogen reduction will be determined by
      weighing the risks of unintended adverse consequences of the procedure itself,
      such as the potential for genotoxicity and allergic reactions, against the cost
      and benefits of its implementation.

PMID- 14714881
TI  - Neuronal expression of enhanced green fluorescent protein directed by 5' flanking
      sequences of the rat aldolase C gene in transgenic mice.
AB  - The rat aldolase C gene encodes a glycolytic enzyme strongly expressed in adult
      brain. We previously reported that a combination of distal and proximal 5'
      flanking sequences, the A + C + 0.8 kilobase (kb) pairs fragments, ensured high
      brain-specific expression in vivo (Skala et al. 1998). We show here that the
      expression pattern conferred by these sequences, when placed in front of the
      chloramphenicol acetyltransferase (CAT) or the enhanced green fluorescent protein
      (EGFP) reporter genes in transgenic mice, is similar to the distribution of the
      endogenous mRNA and protein. Double immunostaining for neuronal or glial cell
      specific markers and for the EGFP protein indicates that the A + C + 0.8 kb
      genomic sequences from the rat aldolase C gene direct a predominant expression in
      neuronal cells of adult brain.

PMID- 14714882
TI  - Clearing and embedding in polyester resin for demonstrating the nerve
      distribution pattern of skeletal muscles.
AB  - The preservation of many stained gross specimens in solution creates some
      difficulties. It is convenient and effective to preserve material in polyester
      resin instead of glycerol. The aim of this study was to determine the usefulness
      of clearing and embedding using polyester resin. The samples consisted of the
      nerve distribution patterns of skeletal muscles stained using Sihler's method.
      The muscles were cleared more successfully and the intramuscular nerve
      distributions were demonstrated better in polyester than in glycerol. The method
      presented here eliminates not only the storage and handling problems of
      specimens, but also problems such as pale stains and the molding of preparations.
      Furthermore, it is more convenient to examine and to photograph specimens cleared
      and embedded in polyester than those stored in glycerol.

PMID- 14714883
TI  - Histological investigation of organisms with hard skeletons: a case study of
      siliceous sponges.
AB  - Siliceous and calcareous sponges commonly are treated with acid to remove the
      spicules prior to embedding and cutting for histological investigations.
      Histology of spiculated sponge tissue represents a challenging problem in sponge
      histotechnology. Furthermore, fluorescence in situ hybridization (FISH), a key
      method for studying sponge-associated microbes, is not possible after acid
      treatment. For a broad range of siliceous sponge species, we developed and
      evaluated methods for embedding in paraffin, methylmethacrylate resins, LR White
      resin and cryomatrix. Different methods for cutting tissue blocks as well as
      mounting and staining sections also were tested. Our aim was to enable
      histological investigations and FISH without prior removal of the spicules. To
      obtain an overview of tissue and skeleton arrangement, we recommend embedding
      tissue blocks with LR White resin combined with en bloc staining techniques for
      large specimens with thick and numerous spicules, but paraffin embedding and
      subsequent staining for whole small specimens. For FISH on siliceous sponges, we
      recommend Histocryl embedding if the spicule content is high, but paraffin
      embedding if it is low. Classical histological techniques are used for detailed
      tissue examinations.

PMID- 14714884
TI  - Rapid and efficient isolation of highly specific antibodies from an antiserum
      against a pool of proteins.
AB  - Antibodies with desired specificity to proteins of interest provide important and
      versatile tools for detecting and localizing specific proteins in organisms. With
      the rapidly increasing number of genes cloned, the demand for antibodies to the
      gene products is increasing greatly. We developed a procedure to isolate highly
      specific antibodies to an insect intestinal mucin (IIM) from a polyclonal
      antiserum, which served as a "library of antibodies," by using an E. coli lysate
      of the IIM cDNA clone. This procedure allows rapid and efficient isolation of
      target protein specific antibodies from a polyclonal antiserum made against a
      pool of antigens.

PMID- 14714885
TI  - A sweet coating--how bacteria deal with sugars.

PMID- 14714886
TI  - The glycosylation of airway mucins in cystic fibrosis and its relationship with
      lung infection by Pseudomonas aeruginosa.

PMID- 14714887
TI  - Structural basis for bacterial adhesion in the urinary tract.

PMID- 14714888
TI  - Crystal structure of an intact human IgG: antibody asymmetry, flexibility, and a
      guide for HIV-1 vaccine design.

PMID- 14714889
TI  - Remnant epitopes generate autoimmunity: from rheumatoid arthritis and multiple
      sclerosis to diabetes.
AB  - Autoimmune diseases are characterized by inflammation and by the development and
      maintenance of antibodies and T lymphocytes against "self" antigens. Although the
      etiology of these diseases is unknown, they have a number of cellular and
      molecular mechanisms in common. Pro-inflammatory cytokines, such as interleukin-1
      (IL-1) and tumor necrosis factor (TNF), are upregulated and activate the
      inflammatory process. Chemokines recruit and activate leukocytes to release
      proteases, including matrix metalloproteinases (MMPs). These proteases degrade
      proteins into remnant fragments, which often constitute immunodominant epitopes.
      Either by direct loading into major histocompatibility complex (MHC) molecules or
      after classical antigen uptake, processing and MHC presentation, these remnant
      epitopes are presented to autoreactive T lymphocytes. Also, posttranslationally
      modified remnant peptides may stimulate B cells to produce autoantibodies. This
      forms the basis of the "Remnant Epitopes Generate Autoimmunity" (REGA) model. We
      have documented evidences for this model in multiple sclerosis (MS), rheumatoid
      arthritis (RA) and diabetes, which are summarized here. Furthermore, three topics
      will be addressed to illustrate the importance of glycobiology in the
      pathogenesis of autoimmune diseases. In MS, gelatinase B or MMP-9 is a pathogenic
      glycoprotein of which the sugars contribute to its interactions with the tissue
      inhibitor of metalloproteinases-1 (TIMP-1) and thus assist in the determination
      of the enzyme activity. In RA, gelatinase B cleaves denatured type II collagen
      into remnant epitopes, some of which constitute immunodominant glycopeptides.
      This implies that immunodominant epitope scanning experiments should preferably
      be done with natural posttranslationally modified glycopeptides, rather than with
      unmodified (synthetic) peptides. Sugars can also be used as molecular probes to
      induce autoimmune diseases. One of the best examples is the induction of acute
      pancreatitis, insulitis and diabetes by streptozotocin. In addition, gelatinase B
      is upregulated in pancreatitis and cleaves insulin. The most efficient cleavage
      by gelatinase B leads to a major insulin remnant epitope.

PMID- 14714890
TI  - Endothelial cell glycosylation: regulation and modulation of biological
      processes.

PMID- 14714891
TI  - Involvement of GAGs in the activity of pro-inflammatory factors.

PMID- 14714892
TI  - Lectin domains on cytokines.

PMID- 14714893
TI  - Cytokines and glycosaminoglycans (GAGs).

PMID- 14714894
TI  - Thomsen-Friedenreich antigen: the "hidden" tumor antigen.

PMID- 14714895
TI  - Glycodynamics of mucin biosynthesis in gastrointestinal tumor cells.
AB  - Glycoproteins found in the secretions and on the surfaces of cancer cells include
      mucins and mucin-like glycoproteins. These molecules have been shown to carry
      antigens that are characteristically expressed on cancer cells, including Tn and
      T antigens and Lewis epitopes. The structures of O-glycans are often abnormal in
      gastrointestinal tumors, or else are present in abnormal amounts, and these
      structures greatly contribute to the phenotype and biology of cancer cells. It
      has been shown that glycans of cancer cells have functional importance in cell
      adhesion, invasion and metastasis. The possible mechanisms leading to these
      cancer-specific changes in carbohydrate structures (termed glycodynamics) involve
      altered mRNA expression and catalytic activities of glycosyltransferases and
      sulfotransferases found in tissues and cells of gastrointestinal tumors. In a
      number of cases it has been possible to correlate enzyme changes with
      oligosaccharide structures. Different mechanisms have been suggested leading to
      the synthesis of cancer-specific Lewis, T and Tn antigens, but the regulation of
      cancer mucin antigens generally appears to be very complex and is poorly
      understood. The expression levels of specific mucin antigens and enzymes in
      gastro-intestinal tumors have diagnostic as well as prognostic value. These
      antigens also have potential for cancer immunotherapy. However, we first need to
      unravel the complexity of the control of glycosylation in cancer cells. Most
      importantly, studies of the functional implications of the glycodynamics in
      cancer cells, as related to cell adhesion and impact on the immune system will
      provide promising directions for future research.

PMID- 14714896
TI  - O-GlcNAc glycosylation and neurological disorders.

PMID- 14714897
TI  - The carbohydrate epitope of the neutralizing anti-HIV-1 antibody 2G12.

PMID- 14714898
TI  - New therapeutics for the treatment of glycosphingolipid lysosomal storage
      diseases.
AB  - Glycosphingolipid lysosomal storage diseases are a small but challenging group of
      human disorders to treat. Although these appear to be monogenic disorders where
      the catalytic activity of enzymes in glycosphingolipid catabolism is impaired,
      the presentation and severity of disease is heterogeneous. Treatment is often
      restricted to palliative care, but in some disorders enzyme replacement does
      offer a significant clinical improvement of disease severity. An alternative
      therapeutic approach termed "substrate deprivation" or "substrate reduction
      therapy" (SRT) aims to reduce cellular glycosphingolipid biosynthesis to match
      the impairment in catalytic activity seen in lysosomal storage disorders. N
      Alkylated imino sugars are nitrogen containing polyhydroxylated heterocycles that
      have inhibitory activity against the first enzyme in the pathway for
      glucosylating sphingolipid in eukaryotic cells, ceramide-specific
      glucosyltransferase. The use of N-alkylated imino sugars to establish SRT as an
      alternative therapeutic strategy is described in cell culture and gene knockout
      mouse disease models. One imino sugar, N-butyl-DNJ (NB-DNJ) has been used in
      clinical trials for type 1 Gaucher disease and has shown to be an effective and
      safe therapy for this disorder. The results of these trials and the prospects of
      improvement to the design of imino sugar compounds for treating Gaucher and other
      glycosphingolipid lysosomal storage disorders will be discussed.

PMID- 14714899
TI  - The mannose-binding lectin (MBL) route for activation of complement.

PMID- 14714900
TI  - Anti-inflammatory properties of specific glycoforms of human alpha1-acid
      glycoprotein.

PMID- 14714901
TI  - The glycosylation of tyrosinase in melanoma cells and the effect on antigen
      presentation.

PMID- 14714902
TI  - Glycobiology of the rheumatic diseases: an update.

PMID- 14714903
TI  - Lupus and the nervous system.

PMID- 14714904
TI  - The ACR nomenclature for CNS lupus revisited.
AB  - Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of
      peripheral and central nervous system manifestations. These manifestations are
      complex and their pathophysiology is poorly understood. NPSLE can precede the
      onset of lupus or occur at any time during its course. The American College of
      Rheumatology (ACR) developed a standardized nomenclature system providing case
      definitions for the neuropsychiatric syndromes of systemic lupus erythematosus
      (SLE) to facilitate and enhance patient classification and reporting requirements
      in clinical research. Estimates of NPSLE prevalence have ranged widely and most
      are based on research conducted before the introduction of ACR case definitions.
      This paper reviews the early experience with the ACR nomenclature use and
      possible future directions for its improvement. The identification and
      categorization of the major neuropsychiatric syndromes in SLE using ACR case
      definitions seems to be adequate, however the mildest and most subjective of the
      syndromes are the most problematic. Even if the definitions in their present form
      might have drawbacks the only way forward is further use of ACR nomenclature,
      pooling data from different populations, and collection of experience as a basis
      for improvement. The acquisition of normative data for ethnic, age and sex
      stratification would extend their usefulness.

PMID- 14714905
TI  - APS and the brain.
AB  - Antiphospholipid antibody syndrome (APS) may present with neurological syndromes.
      Cerebrovascular disease, chorea/ballismus, epileptic seizures, headache,
      cognitive impairment, transverse myelopathy, Devic's syndrome and multiple
      sclerosis-like presentations feature among others. Cerebrovascular disease is one
      of the most common presenting symptoms of APS, second only to deep vein
      thrombosis, and accounts for half of neurological manifestations in patients with
      APS; accelerated atherogenesis and cardioembolism are the most likely mechanisms
      implicated. Though infrequent, chorea is consistently associated with APS; the
      pathogenetic role of antiphospholipid antibodies (APLab) in this case might be
      routed through cerebrovascular disease in some cases and through purely
      immunological pathways in others. Both ischemic and immunological mechanisms have
      been demonstrated in the pathogenesis of epileptic seizures, which may account
      for 7% of neurological manifestations in APS. Although frequent in APS, a
      causative link between APLab and most common types of headache (migraine and
      tension-type headache) is more than dubious. Cognitive impairment may derive from
      a well-defined clinical tableau of multi-infarct dementia. Nevertheless, (highly
      frequent) less severe cognitive impairment has also been associated with the
      presence of APLab in the absence of magnetic resonance findings. A relationship
      between APS and transverse myelopathy seems likely but small numbers in the
      studies published to date preclude definite statements; routinely testing for
      APLab patients with neurological manifestations suggestive of multiple sclerosis
      seems to be unrecommended at the present time.

PMID- 14714906
TI  - Cognitive dysfunction and antiphospholipid antibodies in systemic lupus
      erythematosus.
AB  - Nervous system involvement in systemic lupus erythematosus (SLE) is typically
      diagnosed on the basis of clinical psychiatric and/or neurologic syndromes
      (NPSLE). Neuropsychological tests can be used to assess nervous system integrity
      even in the absence of major NP syndromes. Their application has uncovered
      significant cognitive dysfunction, ranging from mild to severe, in a sizeable
      proportion of SLE patients irrespective of clinical NP status. Cognitive
      dysfunction has now been accepted as a bona fide manifestation of NPSLE. The
      heterogeneity of clinical NPSLE manifestations is paralleled by the diversity of
      cognitive deficits reported in different studies and within different patients.
      The success of attempts to explain these deficits on the basis of potential
      pathogenetic mechanisms, such as antibrain antibodies and proinflammatory
      cytokines, has been uneven. To date, the most robust findings have emerged in
      relation to antiphospholipid antibodies, which carry with them important
      therapeutic implications.

PMID- 14714907
TI  - MRI and the brain in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) can affect any part of the central nervous
      system (CNS) from the cerebrum to the cauda eqina, giving rise to diverse
      neurological mainfestations. Despite clinically apparent symptoms and signs,
      imaging will commonly be normal while at times the magnitude of changes
      demonstrated on MRI may be out of proportion to the clinical presentation. We
      describe the MRI techniques used in CNS imaging and the pattern of presentation
      in SLE.

PMID- 14714908
TI  - Quantitative magnetic resonance imaging in neuropsychiatric systemic lupus
      erythematosus.
AB  - Neuropsychiatric symptoms are common in systemic lupus erythematosus (SLE) but
      are poorly understood. Although there is a wide spectrum of clinical
      manifestations, brain histology often simply shows a bland vasculopathy. Magnetic
      resonance techniques such as magnetic resonance spectroscopy, magnetization
      transfer imaging and diffusion weighted imaging have been used to try to improve
      our understanding of the pathophysiological mechanisms involved in
      neuropsychiatric lupus (NPSLE). This article reviews the current literature on
      the use of these techniques and their possible future role as diagnostic tools in
      NPSLE.

PMID- 14714909
TI  - CNS dysfunction in the antiphospholipid syndrome.
AB  - Though many neurological deficits have been described in the antiphospholipid
      syndrome (APS), only stroke is well established and accepted as a diagnostic
      criterion in this disease. We review clinical data obtained from a large series
      of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter
      disease and behavioral changes in APS or linked to laboratory criteria such as
      antiphospholipid antibodies (aPL). The contribution of animal models to our
      understanding of these manifestations of APS is stressed, especially regarding
      the cognitive and behavioral aspects for which we have established model systems
      in the mouse. These models utilize immunization of mice with beta2-glycoprotein
      I, a central autoantigen in APS, which induces persistent high levels of aPL.
      These mice develop hyperactive behavior after a period of four to five months as
      well as deficits in learning and memory and are potentially valuable as a system
      in which to study the pathogenesis and treatment of cognitive and behavioral
      aspects of APS. Another model we have developed, in which IgG from APS patients
      induce depolarization of brain synaptoneurosomes, may serve as a model for the
      pathogenesis of epilepsy in APS.

PMID- 14714910
TI  - The blood-brain barrier in systemic lupus erythematosus.
AB  - Central nervous system (CNS) involvement may occur in 20-70% of systemic lupus
      erythematosus (SLE) patients where neurological symptoms are overt; this is
      termed neuropsychiatric lupus or NPSLE. This review summarizes evidence that
      damage to the brain endothelium forming the blood-brain barrier (BBB) is a
      contributory factor in NPSLE. The normal CNS is protected by blood-tissue
      barriers at three sites, the brain endothelium (BBB), the choroid plexus
      epithelium (blood-CSF barrier) and the arachnoid epithelium. The tight junctions
      of the barrier layers severely restrict entry of plasma constituents including
      proteins, so that the CSF and brain interstitial fluid contain low levels of
      protein. Methods for diagnosing BBB damage include imaging (CT, MRI) using
      contrast agents, and analysing protein content and profiles of CSF Changes in the
      albumin quotient Qalbumin show evidence for barrier damage, while changes in the
      immunoglobulin (Ig) index can indicate intrathecal antibody production. However,
      BBB damage may be transient, and hence undetected or underestimated. Few
      mechanistic studies exist, but the two main candidate mechanisms for BBB damage
      are microthrombi in cerebral vessels leading to ischaemia, and immune-mediated
      attack and activation of the endothelium leading to local cytokine production.
      Both can result in barrier breakdown. Neurological syndromes could then be
      secondary to damage to the BBB. The implications for treatment of NPSLE are
      discussed.

PMID- 14714911
TI  - Ribosomal P antibodies and CNS lupus.
AB  - Within two years of the recognition of autoantibodies to ribosomal P proteins in
      patients with systemic lupus erythematosus (SLE) an association with anti-P
      autoantibodies with psychosis was noted. While there has been some controversy
      about this association, ample evidence suggests a meaningful relationship between
      anti-P antibodies and central nervous system (CNS) disease. This evidence
      consists of 1) seven independent studies showing a strong relationship between
      anti-P antibodies and CNS disease; 2) longitudinal studies showing fluctuations
      of anti-P antibodies with episodes of psychosis; 3) correlation of anti-P
      antibodies with general disease activity; and 4) acid eluates form lupus renal
      tissue were found to contain anti-P antibodies enriched 30-fold with respect to
      their specific activity in serum heralding a direct role of anti-P antibodies in
      disease expression. Finally, there is evidence that the P protein resides on
      normal cells in an immunologically accessible way and evidence exists that anti-P
      antibodies are able to bind and penerate cells in culture, and once inside cells
      can affect a profound inhibition of protein synthesis in living cells. Taken
      together, these observations provide evidence linking anti-P antibodies to
      various forms of CNS disease. While this is true, there are other autoantibodies
      in SLE patients such as anti-dsDNA and antiglial fibrillary protein which may
      also play a role in the CNS disease of SLE patients. Continued study will inform
      us of the relative contribution of these autoantibodies to CNS disease in SLE
      patients.

PMID- 14714912
TI  - Endothelium and the brain in CNS lupus.
AB  - Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is
      common and results in different clinical manifestations. Several pathogenic
      mechanisms have been suggested to play a role in determining such a variety of
      clinical symptoms. The thrombophilic state associated to the presence of
      antiphospholipid antibodies has been suggested to be responsible for a
      noninflammatory vasculopathy which causes clear ischaemic events as well as
      alterations of the cerebral microcirculation that are likely associated to
      seizures, cognitive dysfunction or psychosis. Although less frequent, a true
      vasculitic process affecting cerebral circulation has also been reported. In both
      cases, brain endothelium does represent the target of the pathogenic mechanisms.
      Brain endothelial cells display peculiar functional and phenotypical
      characteristics in comparison with endothelial cells from other anatomical
      districts, raising the possibility that this might be the reason for its
      susceptibility in lupus disease. We review and present data suggesting that a
      higher and firmer expression of beta 2 glycoprotein I on endothelial cell
      membranes can be responsible for a selective damage/activation by circulating
      anti-beta 2 glycoprotein I, and that antiendothelial cell antibodies crossreact
      with brain endothelium and in some cases, specifically bind brain endothelial
      cells only in lupus patients with central nervous involvement.

PMID- 14714913
TI  - Cerebral haemostasis and antiphospholipid antibodies.
AB  - One of the major clinical concerns of the antiphospholipid syndrome (APS) is the
      propensity of antiphospholipid (aPL) antibodies to cause thrombosis in both the
      large and small vessels of the brain. In this article, we review the current
      understanding of haemostasis in cerebral circulation and discuss this in the
      context of antiphospholipid antibodies. The systemic-defect-local-phenotype
      paradox is of particular importance in this discussion. In this paradigm, a
      systemic defect in thrombosis and haemostasis leads to a localized pattern of
      thrombotic disease because the regional physiological variations in the several
      prothrombotic and anticoagulant factors and the defect interact so as to favour
      thrombosis at a particular site. One possible mechanism of initiation of
      thrombosis in APS is the activation of endothelial cells by aPL that could occur
      in the cerebral vessels and provoke thrombosis. We review the evidence from gene
      knockout mice, other animal models and human postmortem examination studies as to
      which pro- and antithrombotic mechanisms are effecting haemostasis in the
      cerebral circulation. We conclude that there are large deficits in the
      understanding of the regulation ofhaemostasis in the human brain. As a
      consequence there is a lack of knowledge about the effect of aPL on cerebral
      endothelium and thrombosis. Recent developments in gene expression profiling may
      have an impact on our understanding of endothelial function in the brain. More
      research is required.

PMID- 14714914
TI  - Central nervous system lupus: a clinical approach to therapy.
AB  - Management of central nervous system (CNS) involvement still remains one of the
      most challenging problems in systemic lupus erythematosus (SLE). The best
      available evidence for the treatment of CNS lupus is largely based on
      retrospective series, case reports and expert opinion. Current therapy is
      empirical and tailored to the individual patient. Symptomatic, immunosuppressive
      and anticoagulant therapies are the main strategies for the management of CNS
      lupus. The choice depends on the most probable underlying pathogenic mechanism
      and the severity of the presenting neuropsychiatric symptoms. Thrombotic and
      nonthrombotic CNS disease needs to be differentiated and requires different
      management strategies. However, this is often challenging since many, if not most
      CNS manifestations, may be due to a combination of different pathogenic
      mechanisms and multiple CNS events may occur in the individual patient. Patients
      with mild manifestations may need symptomatic treatment only, whereas more severe
      acute nonthrombotic CNS manifestations may require pulse intravenous
      cyclophosphamide. Plasmapheresis may also be added in patients with more severe
      illness refractory to conventional treatment. Recently, the use of intrathecal
      methotrexate and dexamethasone has been reported in a small series of patients,
      with a good outcome in patients with severe CNS manifestations. Anticoagulation
      is warranted in patients with thrombotic disease, particularly in those with the
      antiphospholipid syndrome (APS). This article reviews the clinical approach to
      therapy in patients with CNS lupus.

PMID- 14714915
TI  - Headache and systemic lupus erythematosus.
AB  - Headache is a common feature in patients with systemic lupus erythematosus (SLE)
      and represents a significant source of patient discomfort. The exact prevalence
      of headache in SLE is unknown. The results of different studies widely vary, most
      likely due to the use of different classification for headache and the lack of
      controls in most studies. The relationship between headache and SLE is also
      unclear since it is difficult to determine which degree and type of headaches can
      be explained on the basis of chronic illness, or as part of the disease spectrum
      of SLE. No pathogenic mechanism has so far been described that can fully explain
      headache induced by SLE. The role of circulating cytokines, vascular injury,
      neuronal damage or antiphospholipid antibodies (aPL) in the development of
      headache in SLE patients is also a matter of debate. Other concomitant causes
      such as infection or hypertension should be excluded before assuming that
      headache is a feature of SLE activity. Therapeutic approach of headache SLE
      related remains empirical and based on clinical experience.

PMID- 14714916
TI  - A psychiatric perspective on the therapy of psychosis in systemic lupus
      erythematosus.
AB  - A brief description of psychosis in the general psychiatric setting and its
      treatment using antipsychotic agents including 'atypical' drugs. A review of the
      prevalence of neuropsychiatric syndromes in lupus (using The American College of
      Rheumatology standardized definitions) from recent studies showing wide variation
      in reported rates. Underlying pathophysiologic mechanisms postulated for
      neuropsychiatric manifestations of lupus are reviewed with implications for
      treatment. The use and success of intravenous pulsed cyclophosphamide (singly and
      in combination with methylprednisiolone) for severe neuropsychiatric psychosis is
      reviewed.

PMID- 14714917
TI  - The epidemiology of preterm birth.
AB  - The epidemiologic characteristics of women who deliver their infants before term
      birth are clues to the cause of this most important obstetric problem.

PMID- 14714918
TI  - The physiology of uterine contractions.
AB  - Studies in animals and humans indicate that uterine performance can be
      successfully monitored during pregnancy using uterine electromyography. Uterine
      electromyography could be used to better define management in a variety of
      conditions associated with human labor. The potential benefits of the proposed
      instrumentation and method include: reducing the rate of preterm delivery,
      improving maternal and perinatal outcome, monitoring treatment, decreasing
      cesarean-section rate, and providing research methods to better understand
      uterine function.

PMID- 14714919
TI  - Infection as a cause of preterm birth.
AB  - In summary, there is little question that intrauterine and some extrauterine
      infections play important roles in the etiology of early, spontaneous, preterm
      labor and PROM. Disappointing are the mixed results from various treatment
      attempts, usually with antibiotics, to reduce the preterm birth rate. Clearly, a
      better understanding of the pathways leading from infection to preterm birth will
      be necessary to develop effective interventions to reduce infection-related
      preterm delivery. Research must also address the question of individual
      susceptibility to infections and the influence of other exposures that may
      moderate the association between infection and preterm birth.

PMID- 14714920
TI  - Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol.
AB  - Preterm birth is a major complication of pregnancy and remains a leading cause of
      neonatal morbidity and mortality worldwide. Improvements in the authors'
      understanding of the pathophysiology of preterm labor have led to the development
      of novel diagnostic tools of use to identify women at greatest risk for preterm
      birth. Currently two FDA-approved biochemical tests are available in the United
      States: (1) fetal fibronectin and (2) salivary estriol. The presence of a
      positive fetal fibronectin test in the midtrimester of pregnancy is strongly
      associated with early spontaneous preterm birth. In contrast, a positive salivary
      estriol test is associated with late preterm birth, thus limiting its clinical
      use. Both tests have low test sensitivity and are currently used clinically for
      their negative predictive values. That is, women who screen negative are at very
      low risk for preterm birth and, thus, no interventions are indicated to prevent
      preterm birth. Women with a positive test are at increased risk and would be
      candidates for intervention. One of the main limitations of fetal fibronectin and
      salivary estriol, and an array of other proposed markers, is the fact that while
      these markers may aid in identification of women at increased risk for preterm
      birth, the authors currently have no clearly effective obstetric interventions
      for preterm-birth prevention in these high-risk women. Use of tocolytics,
      antimicrobials, or progesterone therapy currently has limited or unproven benefit
      in the management of women deemed at increased risk using these markers. Thus,
      until effective targeted obstetric interventions are available, the use of
      biochemical markers to identify women at increase risk for preterm birth remains
      largely research tools.

PMID- 14714921
TI  - Evaluation of the cervix by ultrasound for the prediction of preterm birth.
AB  - Across numerous investigations and study populations, the relationship between
      shortened cervical length and spontaneous preterm birth is consistent and
      compelling. However, one must recognize the imperfect test characteristics of
      cervical ultrasound for predicting prematurity, particularly in low-risk
      populations. It should be clear that this relationship supports interactions with
      the other anatomic components and interactive pathways that comprise the
      spontaneous, preterm-birth syndrome. In summary, the clinical usefulness of these
      observations will be realized only through further investigation into the
      pathophysiology of spontaneous preterm birth and through controlled, clinical
      intervention trials.

PMID- 14714922
TI  - Current status of home uterine activity monitoring.
AB  - A comprehensive evidence-based review of the clinical data leads to the
      conclusion that if patients at high risk for preterm birth (eg, prior preterm
      birth because of preterm labor, twins and higher-order multiple gestation, women
      who have preterm labor during the current pregnancy tocolyzed effectively) use
      the comprehensive system of HUAM correctly (ie, daily nursing care and twice
      daily monitoring) with appropriate alarm rates and sensitive monitors, the
      incidence of early diagnosis of preterm labor, effective prolongation of
      pregnancy with fewer preterm births, and a reduction in neonatal morbidity is
      always demonstrated when the study group is compared with a control group
      consisting of women receiving standard care available to obstetricians in the
      United States. The authors expect that there will always be arguments regarding
      whether the monitor or the nurse contributes most to preterm birth reduction.
      Even when the alerts of detected contractions or patient-reported symptoms are
      sounded, the issue of prompt and effective medical intervention will always be
      hotly debated. The appropriate research design that tests HUAM while allowing
      various diagnostic and treatment modalities that physicians employ around the
      United States must be individualized. Physicians must make the decision, based on
      the evidence, regarding whether or not this system would benefit their patients.
      While investigators argue about research designs and statistical analyses,
      physicians simply want the best outcomes for their patients, which is what women
      and the whole of society also want. Based on the available evidence, it is clear
      that when the comprehensive system of HUAM is used appropriately in the right
      patients, everyone benefits.

PMID- 14714923
TI  - Acute management of preterm labor.
AB  - We are continually reminded that the preterm birth rate has failed to improve; in
      fact, it has increased over the last 20 years. Much of this increase is related
      to the tremendous strides made by neonatologists and the resulting increased
      willingness of obstetricians to deliver preterm babies from hostile intrauterine
      environments. However, there is still much to learn concerning the pathogenesis,
      accurate early detection, treatment, and prevention of spontaneous preterm labor.
      This article concentrates on the clinical diagnosis and acute management of this
      enigmatic clinical problem.

PMID- 14714924
TI  - Antenatal corticosteroids for fetal maturation in women at risk for preterm
      delivery.
AB  - The available data unambiguously support the beneficial, short-term fetal effects
      of antenatal corticosteroids in women at risk for preterm delivery. There are
      still several incompletely addressed questions, including the use of
      corticosteroids in women with preterm premature rupture of membranes, the optimal
      corticosteroid preparation to be used, and the impact of repeated dosing. These
      issues are discussed in this review from the perspective of recent scientific
      evidence on the mechanisms responsible for positive short-term effects on
      survival and possible harmful long-term effects.

PMID- 14714925
TI  - The therapeutic value of maintenance tocolysis: an overview of the evidence.
AB  - The results obtained from current systematic overview do not support the routine
      administration of maintenance tocolytic treatment after parenteral tocolytic
      therapy has halted acute preterm labor. Eliminating or reducing such routine
      maintenance therapy, therefore, could substantially decrease costs and side
      effects associated with managing preterm labor without compromising perinatal
      outcomes. It remains to be elucidated whether it will become possible to
      accurately identify some groups of pregnancies for which maintenance tocolysis
      would be beneficial.

PMID- 14714926
TI  - Special considerations for the HIV-infected patient with preterm labor.
AB  - It is essential that women admitted for PTL have a confidential review of
      maternal history and prenatal record for HIV serostatus. Combination ARV therapy
      should be continued during tocolysis of PTL and, if tocolysis fails, through
      delivery. Counseling and rapid HIV testing should be performed in the intrapartum
      or postnatal periods if the woman's serostatus has not been determined. Women
      identified as being HIV infected who are in labor should be treated with (1) ZDV
      in labor and for 6 weeks to the neonate, (2) NVP single dose to the mother in
      labor and single dose to the neonate, (3) ZDV-3TC in labor and to the neonate for
      1 week, or (4) NVP (as above) and the ZDV regimen (as above). Cesarean delivery
      should be recommended to all women when the most recent viral load is greater
      than or equal to 1000 copies/mL or is unknown. Those charged with the care of HIV
      infected pregnant women should make frequent use of the Public Health Service
      Website (http://www.aidsinfo.nih.gov), which provides a regularly updated,
      practical, and thorough guide to management of patients who have HIV.

PMID- 14714928
TI  - Commitment to philosophy, teacher efficacy, and burnout among teachers of
      children with autism.
AB  - Variables that may be related to burnout in teachers of students with autism,
      including commitment to an underlying philosophy of a treatment and professional
      self-efficacy, were explored. Teachers using one of two different treatment
      approaches to autism participated: those using Applied Behavior Analysis (n =
      34), and those using TEACCH (Treatment and Education of Autistic and Related
      Communication-Related Handicapped Children) (n = 30). Participants completed the
      Autism Treatment Philosophy Questionnaire, developed by the authors to
      differentiate between the philosophy of the approaches; Teacher Efficacy Scale,
      and Maslach Burnout Inventory. Results indicate a significant difference in
      philosophical commitment between the groups, but no differences in teaching
      efficacy or burnout. The relationship between a commitment to one's teaching
      approach and certain dimensions of teaching efficacy and burnout was found to be
      significant. Implications include the need for adequate training of teachers of
      students with autism.

PMID- 14714927
TI  - The symptoms of autism spectrum disorders in adolescence and adulthood.
AB  - This article describes the symptoms of autism spectrum disorders (ASD) manifested
      by 405 individuals between the ages of 10 and 53 years, all of whom had an ASD
      diagnosis. Data were collected using the Autism Diagnostic Interview-Revised (ADI
      R) to assess the pattern of autism symptoms in adolescence and adulthood.
      Findings include that although virtually all sample members met the criteria for
      Autistic Disorder earlier in their childhood, just over half (54.8%) would have
      met autism criteria if current scores were used to complete the diagnostic
      algorithm; that adolescents were more likely to improve in the Reciprocal Social
      Interaction domain than the adults, whereas the adults were more likely to
      improve in the Restricted, Repetitive Behaviors and Interests domain, and there
      were no differences in severity of symptoms between cohorts in the Communication
      domain; and that individual symptoms showed unique trajectories, with greatest
      symptom abatement between lifetime and current ADI-R ratings for speaking in at
      least three-word phrases and the least symptom improvement for having
      friendships. Findings were interpreted in the context of life course development,
      reformulations of diagnostic criteria, and changing service contexts for
      individuals with autism spectrum disorders.

PMID- 14714929
TI  - Measuring pervasive developmental disorders in children and adolescents with
      mental retardation: a comparison of two screening instruments used in a study of
      the total mentally retarded population from a designated area.
AB  - The performance of two screening instruments for Pervasive Developmental
      Disorders was studied in the total population of participants with mental
      retardation between 4 and 18 years (n = 1059) in Friesland, a northern province
      of the Netherlands. Parents completed the Autism Behavior Checklist (ABC), staff
      completed the Scale of Pervasive Developmental Disorder in Mentally Retarded
      Persons (PDD-MRS). The screening instruments were related to the Autism
      Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule-Generic
      for 184 participants. The agreement between ABC and PDD-MRS was fair (kappa =
      .24). The ABC had a better criterion-related validity compared with the Autism
      Diagnostic Interview-Revised, and the PDD-MRS compared to the Autism Diagnostic
      Observation Schedule-Generic. However, related to the clinical classification,
      both instruments performed equally well. Concluding, the ABC and PDD-MRS
      partially identify the same cases related to external criteria. In addition, each
      instrument has its own contribution. Both instruments are valuable in detecting
      children who are at high risk for PDD.

PMID- 14714930
TI  - Language and other regression: assessment and timing.
AB  - Understanding of regression in autism has been hampered by variability in
      parental and clinical recognition and reporting of lost skills. This study
      introduced an instrument, the Regression Supplement Form, intended to supplement
      the Autism Diagnosis Interview-Revised and yield precise information about the
      types and timing of regression and events concurrent with loss and regain of
      skills. Data were collected from parents of 44 children (38 male, 6 female; mean
      age = 6 years) with Autistic Spectrum Disorder (37 Autistic Disorder, 7 Pervasive
      Developmental Disorder-Not Otherwise Specified). Parental responses on the Autism
      Diagnosis Interview-Revised indicated loss of skills during early development.
      The profile of regression that emerged included loss of skills between 18 and 21
      months, on average, with language-only regression less common than loss of other,
      nonlanguage skills only or of full regression (loss of language and other
      skills). The onset of regression typically was gradual in nonlanguage areas and
      split between gradual and sudden loss for language skills. Some of the children
      were developing atypically before they lost other, nonlanguage skills, that is,
      their age at first words was delayed until age 2 years or older. Parents tended
      to attribute loss to medical factors such as immunizations. Many of the children
      regained some of the lost skills when they were 3.5-5 years of age, with
      therapeutic and instructional interventions given credit for the regain.

PMID- 14714931
TI  - Reliability and validity of an assessment instrument for anxiety, depression, and
      mood among individuals with mental retardation.
AB  - A review of the literature revealed that there was no adequate assessment
      instrument available that screens comprehensively for anxiety and depression in
      persons with mental retardation. The purpose of this research was to develop the
      Anxiety, Depression, and Mood Scale (ADAMS), an instrument intended to fill this
      gap. We developed a preliminary rating scale that included 55 symptom items. We
      examined the factor structure of these items by an exploratory factor analysis of
      behavior ratings on 265 individuals. A five-factor solution emerged that was both
      statistically sound and clinically meaningful. These factors were labeled
      "Manic/Hyperactive Behavior," "Depressed Mood," "Social Avoidance," "General
      Anxiety" and "Compulsive Behavior." We validated this solution by conducting a
      confirmatory factor analysis on ratings of 268 additional individuals. Model fit
      was acceptable. Internal consistency of the subscales and retest reliability for
      both the total scale and the subscales was high. Interrater reliability was
      satisfactory. The validity of the ADAMS was assessed with a clinical sample of
      129 individuals with mental retardation who were seen in a psychiatric clinic;
      this provided additional support for the subscales. The ADAMS appears to be a
      psychometrically sound instrument for screening anxiety, depression and mood
      disorders among individuals with mental retardation.

PMID- 14714932
TI  - Parent reports of sensory symptoms in toddlers with autism and those with other
      developmental disorders.
AB  - The Short Sensory Profile was used to assess parental report of sensory
      reactivity across four groups of young children (n = 102). Groups were autism (n
      = 26), fragile X syndrome (n = 20), developmental disabilities of mixed etiology
      (n = 32), and typically developing children (n = 24). Groups were comparable on
      overall mental age (x = 22 months), and clinical groups were comparable on
      chronological age (x = 31 months). Significant differences were detected at alpha
      <.01 for tactile sensitivity [F(3,99) = 10.01], taste/smell sensitivity [F(3,99)
      = 11.63], underreactive/seeks stimulation [F(3,99) = 4.56], auditory filtering
      [F(3,99) = 19.67], and low energy/weak muscles [F(3,99) = 14.21]. Both children
      with fragile X syndrome and children with autism had significantly more sensory
      symptoms overall than the two comparison groups, and children with autism did not
      differ significantly from children with fragile X syndrome. Both groups were more
      impaired than developmentally delayed and typically developing children in
      tactile sensitivity and auditory filtering. Children with autism were more
      abnormal in responses to taste and smell than all other groups. Children with
      fragile X syndrome were more abnormal than all other groups in low energy/weak
      muscles. Sensory reactivity of children with developmental delays was comparable
      to mental age-matched typically developing toddlers. Correlational analyses
      indicated that neither overall developmental level nor IQ was related to abnormal
      sensory reactivity in children with autism or general developmental disorders.
      However, abnormal sensory reactivity had a significant relationship with overall
      adaptive behavior.

PMID- 14714933
TI  - Postural stability in children with autism spectrum disorder.
AB  - Maintaining upright posture is a complex process involving multiple afferent
      systems. The aim of this study was to measure the postural stability of children
      with Autism Spectrum Disorder (ASD) compared with children with typical
      neurodevelopment and to measure the relative contributions of the visual,
      somatosensory, and vestibular afferent systems in each group. Eight boys with ASD
      and eight age-, race-, and gender-matched controls participated in this study
      using force platform technology with customized software to measure postural sway
      under conditions designed to eliminate or modify visual and somatosensory input.
      Children with ASD had significantly larger sway areas under all test conditions
      in which afferent input was modified. These results are consistent with a deficit
      in the integration of visual, vestibular, and somatosensory input to maintain
      postural orientation.

PMID- 14714934
TI  - Development and evaluation of a computer-animated tutor for vocabulary and
      language learning in children with autism.
AB  - Using our theoretical framework of multimodal processing, we developed and
      evaluated a computer-animated tutor, Baldi, to teach vocabulary and grammar for
      children with autism. Baldi was implemented in a Language Wizard/Player, which
      allows easy creation and presentation of a language lesson involving the
      association of pictures and spoken words. The lesson plan includes both the
      identification of pictures and the production of spoken words. In Experiment 1,
      eight children were given initial assessment tests, tutorials, and reassessment
      tests 30 days following mastery of the vocabulary items. All of the students
      learned a significant number of new words and grammar. A second within-subject
      design with six children followed a multiple baseline design and documented that
      the program was responsible for the learning and generalization of new words. The
      research indicates that children with autism are capable of learning new language
      within an automated program centered around a computer-animated agent,
      multimedia, and active participation and can transfer and use the language in a
      natural, untrained environment.

PMID- 14714935
TI  - Effect of sensory feedback on immediate object imitation in children with autism.
AB  - This study examined the effect of sensory feedback (e.g., flashing lights and
      sound) on the imitation performance of children with autism and typical children
      group-matched for mental age. Participants were administered an immediate object
      imitation task with six novel toys constructed for this study: three with a
      sensory effect that could be activated by imitating the modeled action and three
      without a sensory effect. Although overall imitation performance did not differ
      significantly between the two groups, the imitation performance of the
      participants with autism was significantly higher with sensory toys than with
      nonsensory toys. Typical participants' imitation performance did not differ
      between the two sets of toys. Both groups played significantly more with the
      sensory toys during free play, indicating that sensory toys were more reinforcing
      for both groups. Additional results demonstrated that typical children used
      significantly more social behaviors during imitation than children with autism,
      but they did not differ in object-oriented behaviors, replicating previous
      findings. It is argued that children with autism may be less motivated to imitate
      by social interaction, but may be motivated to imitate to receive a nonsocial
      reward (sensory feedback).

PMID- 14714936
TI  - Examining the effectiveness of an outpatient clinic-based social skills group for
      high-functioning children with autism.
AB  - Although social skills group interventions for children with autism are common in
      outpatient clinic settings, little research has been conducted to determine the
      efficacy of such treatments. This study examined the effectiveness of an
      outpatient clinic-based social skills group intervention with four high
      functioning elementary-aged children with autism. The group was designed to teach
      specific social skills, including greeting, conversation, and play skills in a
      brief therapy format (eight sessions total). At the end of each skills-training
      session, children with autism were observed in play sessions with typical peers.
      Typical peers received peer education about ways to interact with children with
      autism. Results indicate that a social skills group implemented in an outpatient
      clinic setting was effective in improving greeting and play skills, with less
      clear improvements noted in conversation skills. In addition, children with
      autism reported increased feelings of social support from classmates at school
      following participation in the group. However, parent report data of greeting,
      conversation, and play skills outside of the clinic setting indicated significant
      improvements in only greeting skills. Thus, although the clinic-based
      intervention led to improvements in social skills, fewer changes were noted in
      the generalization to nonclinic settings.

PMID- 14714937
TI  - The CBCL and the identification of children with autism and related conditions in
      Brazil: pilot findings.
AB  - The Child Behavior Checklist (CBCL)/4-18 is one of the few standardized means
      available for assessing child mental health in Brazil. In this context, the
      identification of a specific pathology such as autism by the CBCL/4-18 is
      relevant. To examine the validity of the CBCL/4-18 for the identification of
      autism, the CBCL/4-18 was applied to 101 children: 36 with autism and related
      conditions, 31 with other psychiatric disorders, and 34 schoolchildren. Children
      ranged in age from 4 to 11 years. A CBCL factor called Autistic/Bizarre and the
      narrow-band Thought Problems scale differentiated autistic conditions from other
      psychiatric disorders and schoolchildren. CONCLUSION: The CBCL/4-16 can identify
      autistic children in clinical and school settings in Brazil.

PMID- 14714938
TI  - Adolescent with Autistic Spectrum Disorder and some Obsessive-Compulsive Disorder
      behavior.

PMID- 14714939
TI  - Central auditory processing assessments. Introduction.

PMID- 14714940
TI  - Anatomophysiology of the central auditory nervous system: basic concepts.
AB  - The purpose of this review is to provide an overview of the central auditory
      nervous system (CANS). Three main relay nuclei are located between the auditory
      nerve and the primary auditory cerebral cortex: 1- the cochlear nucleus, 2- the
      contralateral inferior colliculus and 3- the contralateral medial geniculate
      body. Some fibers of this main ascending pathway branch off to other nuclei such
      as the nuclei of the superior olivary complex and the nucleus of the lateral
      lemniscus. Fiber tracts connect the two sides of the ascending pathway at several
      levels, in such a manner that each ear projects heavier to the contralateral
      temporal cortex. As sensory information travels within the CANS, its processing
      occurs not only in a serial order but also in a parallel manner resulting a
      highly efficient and redundant system. Finally, this review put forth a model of
      central auditory processing that can serve as the basis for evaluating and
      addressing the needs of eventual revalidation.

PMID- 14714941
TI  - Auditory perception in the child.
AB  - The development of auditory perception in the infant starts in utero and
      continues up to the age of 9-10 years. We shall examine the various stages, the
      various acoustic parameters and the segmental level. Three stages are important:
      from 7 months onwards: first perceptual reorganization; between 7 and 12 months:
      second perceptual reorganization; from 10 to 24 months: segmentation of the
      spoken word. We will note the evolution between 2 and 6 years and between 6 and 9
      years: 9 years being the critical age--switching from global treatment to
      analytic treatment of utterances. We will then examine musical perception and we
      note that at the prelinguistic level it is the same perceptive units that handle
      verbal sequences and musical sequences. The stages of musical perception are
      parallel to those for speech. Bigand posed the question: "should we see in these
      hierarchies, and in their importance to perception, the manifestation of an
      overall cognitive constraint restricting the handling of long sequences of
      acoustic events (including language) and why not even for all processes dealing
      with symbolic information".

PMID- 14714942
TI  - Central auditory processing assessment.
AB  - As the acoustic information travels within the central auditory nervous system,
      the processing of the signal undergoes several levels of serial and parallel
      "bottom-up" processing influenced by high level cognitive "top-down" processes.
      Because the multiple location of the operational sites, the central auditory
      deficits are frequently quite subtle and need a test battery approach to be
      identified. Each of the four principal processes has at least to be tested: the
      closure task, the dichotic ability, the temporal ordering task and the binaural
      interaction function. The purpose of this review is to provide an overview of the
      psychoacoustic test procedures of identifying lesions or dysfunction's in the
      central auditory system.

PMID- 14714943
TI  - The role of evoked potentials (EPs) in the assessment of the human central
      auditory nervous system (CANS).
AB  - This paper presents an overview of the use of EPs in the assessment of the CANS.
      Emphasis is laid on recent developments and research efforts centered on
      appraising how the auditory neural code is processed by the central pathways. It
      is shown how, in addition to their classical site-of-lesion testing role, EPs
      can, especially when combined with ecological (mostly speech-like) stimuli, yield
      highly valuable information on the neurophysiological processes leading to the
      perception of auditory objects as well as speech. Special space is devoted to the
      Mismatch Negativity that currently provides the only objective measure of the
      accuracy with which the CANS detects auditory and phonetic contrasts.

PMID- 14714944
TI  - Functional neuroimaging of auditory processing.
AB  - There is a complex functional organization of the central auditory system from
      the brainstem to primary and associative auditory cortices. Functional
      neuroimaging has been used to visualize and confirm the spatial distribution of
      brain activation in temporal areas for the processing of simple acoustic stimuli.
      Brain activity is much more complex for words, and different networks can be
      recruited when phonological, lexical and semantic levels of processing are
      engaged.

PMID- 14714945
TI  - Central auditory processing assessment: a French-speaking battery.
AB  - Based on the American Speech-Language-Hearing Association (ASHA) Consensus
      Statement on central auditory processing and models for their exploration, a
      battery of audiological tests (Bilan Auditif Central--BAC) has been designed in
      French. The BAC consists of four types of psycho-acoustic tests: a speech-in
      noise test, a dichotic test, a temporal processing test and a binaural
      interaction test. We briefly describe the rationale of these tests. The BAC is
      available in digital format. Descriptive statistics were computed on data
      obtained from 668 subjects divided into 15 age-groups ranging from 5 to 85 years
      old or over. All subjects had no complaints regarding hearing loss, normal tonal
      audiometry, and normal intelligence. Tests scores of the speech-in-noise test,
      the dichotic test and the binaural interaction test showed a normal distribution.
      Test scores of the temporal processing test did not follow a normal distribution.
      Effects of maturation and involution were clearly visible for all tests. The low
      correlation between scores obtained from the four tests pointed to the need for a
      battery of several tests to assess central auditory processing. We claim that the
      reported scores represent standard norms for the normal French-speaking
      population, and believe that the tests will be useful for evaluation of central
      auditory processing.

PMID- 14714946
TI  - Central auditory processing disorders: some cohorts studies.
AB  - This paper presents an overview of the use of a French-speaking battery for the
      assessment of a central auditory processing disorder (CAPD) in a variety of
      clinical populations: prematurely born children; 8 years old children who had
      otitis media with effusion in early infancy; children with learning problems and
      dyslexia; French-speaking children attending Dutch and English schools; adults
      with King-Kopetzky syndrome and elderly hearing aids users. Population
      characteristics of each of these groups are presented and discussed.

PMID- 14714947
TI  - Management of auditory processing disorders.
AB  - For the initial management of auditory processing disorders, it is essential to
      refer to a theoretical model which conceptualizes the functioning of these
      processes in their interaction with the higher cognitive functions of language
      and its representations stored in LTM, attention and memory. Such a
      conceptualization highlights, therefore, the need for a multidisciplinary
      approach to this type of disorder. On this theoretical basis, this article
      proposes, firstly, to describe for each of the central auditory processes (ASHA)
      certain clinical signs of a disorder at this level together with the central
      auditory assessment tests which allow more specific targeting of these
      manifestations. This article then aims to group, non-exhaustively, different
      types of therapeutic approach proposed in the literature, according to whether
      they concentrate on "Bottom-Up" processing concerned in the transduction of the
      acoustic message and/or rather on "Top-Down" processing, activated in the
      interpretation of the auditory information.

PMID- 14714948
TI  - Causes of non-B, non-C hepatocellular carcinoma: is TTV a causative agent?

PMID- 14714949
TI  - Corticosteroid pulse the therapy for the treatment of cholesterol embolic
      disease.

PMID- 14714950
TI  - Another possibly important function of VEGF related to polyneuropathy.

PMID- 14714951
TI  - Autoimmune aspects of pulmonary hypertension in collagen vascular diseases.

PMID- 14714952
TI  - A detective story for biomedical footprints towards new therapeutic interventions
      in diabetic nephropathy.
AB  - The biochemistry of protein modifications in human disease teaches us a number of
      lessons as it reveals factors and pathways implicated in the genesis of human
      pathology. For instance, diabetic renal damage is associated with a variety of
      stresses, e.g., glycemic stress resulting from hyperglycemia, oxidative stress
      from reactive oxygen species, carbonyl stress from reactive carbonyl compounds,
      and nitrosative stress from reactive nitrogen species. Proteins are particularly
      attractive targets for product analysis. Protein modifications are much more
      specific and stable biomarkers of the disease than lipids and other metabolites,
      and thus serve as footprints of biochemical processes. Their quantitative
      analysis not only facilitates better understanding of the physiopathology but
      also offers new therapeutic insight. In this review, we delineate oxidative
      protein modifications existing in diabetic nephropathy and discuss therapeutic
      perspectives towards the development of new classes of renoprotective agents.

PMID- 14714953
TI  - TT virus-positive hepatocellular carcinoma arising from non-cirrhotic liver in an
      elderly man.
AB  - A 43-mm hepatic tumor was incidentally detected by computed tomography in a 72
      year-old man. Liver function test results were normal. Serum hepatitis B, C and G
      viruses were negative, while serum TT virus was positive. Autoantibodies were
      negative. The patient had no history of alcohol consumption. The tumor was found
      to be a moderately differentiated hepatocellular carcinoma (HCC) from a resected
      specimen. Neither lobular inflammation nor fibrosis was observed in the
      surrounding liver. Intrahepatic hepatitis B virus was not detected. This is a
      case of non-B, non-C HCC positive for only TT virus arising from a non-cirrhotic
      liver.

PMID- 14714954
TI  - Ileal schwannoma in which blood loss scintigraphy was useful for diagnosis.
AB  - An 85-year-old woman was hospitalized with severe melena of unknown origin. Upper
      gastrointestinal (GI) endoscopy and lower GI endoscopy did not detect the origin
      and we could not establish any diagnosis. To explore the bleeding site, 99mTc-HSA
      blood loss scintigraphy was performed and a tumor of the small intestine was
      suspected. Fluoroscopic examination of the small intestine and abdominal CT scan
      confirmed an ileal tumor measuring 4x3 cm. The mass was a well-demarcated tumor
      about 80 cm proximal to Bauhin's valve. Partial resection of the ileum was
      carried out and the tumor was histologically diagnosed as schwannoma. Thereafter,
      there has been no recurrence of melena nor metastasis of the tumor. It is thought
      that blood loss scintigraphy is a useful method for unexplained exacerbation of
      melena.

PMID- 14714955
TI  - Association of intestinal malignant lymphoma and ulcerative colitis.
AB  - A 42-year-old woman with refractory ulcerative colitis (UC) developed ascites,
      pleural effusion, pretibial edema and severe anemia. Colonofiberscopic
      examination showed a bulky submucosal tumor in the sigmoid colon, which was
      histologically diagnosed as malignant lymphoma (diffuse large, B cell type). The
      lymphoma was resistant to chemotherapy. Autologous peripheral blood stem cell
      transplantation (PBSCT) was effective; however, she died of severe infection
      after the second PBSCT. Although the association of intestinal lymphoma with UC
      is rare, lymphoma should be taken into consideration when the clinical course of
      UC is atypical or when UC is refractory to therapy.

PMID- 14714956
TI  - Three cases of liver injury caused by Sennomotokounou, a Chinese dietary
      supplement for weight loss.
AB  - Dietary supplements have become very popular worldwide because they are believed
      to be safe with few side effects. Here, we report three cases of liver injury
      caused by Sennomotokounou, a Chinese dietary supplement for weight reduction. All
      patients developed acute hepatotoxicity and recovered spontaneously after
      withdrawal of dietary product. This product contains fenfluramine, n-nitroso
      fenfluramine, and dried thyroid tissue powder. In Japan, the regulatory agency
      for drug and food safety received 120 reports of hepatotoxicity associated with
      Sennomotokounou between 2000 and 2002. Physicians should inquire about the use of
      dietary supplements whenever patients present with unexplained acute liver
      dysfunction.

PMID- 14714957
TI  - Decrease of beta-cells and increase of alpha-cells in a diabetic patient with
      mitochondrial DNA 3243 (A-->G) mutation.
AB  - We report here a case of a 53-year-old woman with mitochondrial 3243 (A-->G)
      mutation diabetes. Diabetes mellitus was diagnosed at 39 years of age. At 50
      years of age, cardiomyopathy and hypothyroidism were noted. At 53 years of age,
      the patient was admitted to our hospital for treatment of necrotic ulceration of
      toes. However, she died of massive heart failure. Pathological examination at
      autopsy showed a decrease in size, number, and acidophilicity of islets in the
      pancreas. Immunohistochemical stain revealed a decrease in the beta-cell
      population to 20.5+/-9.2% and a relative increase in alpha-cell population to
      48.6+/-11.5%.

PMID- 14714958
TI  - Ectopic ACTH syndrome due to thymic atypical carcinoid treated with combination
      chemotherapy of cisplatin and etoposide.
AB  - A 21-year-old woman with Cushing's syndrome presented with a mediastinal tumor.
      Ectopic ACTH syndrome was diagnosed and the tumor was resected. The
      histopathological diagnosis was thymic atypical carcinoid. Despite all tumor
      lesions having been resected, the tumor relapsed and multiple metastatic lesions
      grew aggressively. Combination chemotherapy with cisplatin and etoposide (VP16)
      was administered to control tumor progression, and achieved marked therapeutic
      effects. Maintenance chemotherapy with carboplatin and VP16 achieved long-term
      tumor control. This case indicates that some patients with atypical carcinoid
      tumor are good responders to chemotherapy with platinum agents and VP16.

PMID- 14714960
TI  - Renal cholesterol embolic disease effectively treated with steroid pulse therapy.
AB  - A 65-year-old man developed acute renal failure with eosinophilia two weeks after
      a coronary bypass operation and angiography. Renal biopsy revealed cholesterol
      crystal embolism (CCE) in glomeruli and arterioles. Low-dose corticosteroid
      therapy failed to recover the renal function; further deterioration of renal
      function and peripheral ischemic symptoms such as livedo reticularis and blue
      toes occurred. However, steroid pulse therapy successfully attenuated CCE-induced
      renal failure and eosinophilia. It is suggested that steroid pulse therapy might
      be effective to treat CCE-induced renal failure and eosinophilia could be a
      useful marker for activity of CCE.

PMID- 14714959
TI  - Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused
      severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic
      patient with diabetic nephropathy; a case report and analysis of the potential
      for hypercalcemia.
AB  - Vitamin D has been used for topical treatment of psoriasis, and 22-oxacalcitriol
      (OCT), shown to be less calcemic, was developed for the topical treatment of
      psoriasis in Japan. Recently, we treated a psoriatic patient with diabetic
      nephropathy who developed severe hypercalcemia with exacerbation of chronic renal
      failure by the use of topical OCT. Analysis of the reported cases demonstrated
      that both the severity of psoriasis and renal dysfunction are critical factors in
      the induction of hypercalcemia in the topical treatment of psoriasis. Therefore,
      we must pay attention to the severity of psoriasis, especially when complicated
      by renal function impairment. Regular monitoring of Ca and renal function is
      essential to avoid life-threatening hypercalcemia from the topical treatment with
      vitamin D analogues.

PMID- 14714961
TI  - Mixed cryoglobulinemia due to chronic hepatitis C with severe pulmonary
      involvement.
AB  - Pulmonary involvement in cryoglobulinemia usually is mild. We present a rare case
      of severe lung involvement in mixed cryoglobulinemia. A 73-year-old woman with
      cryoglobulinemic glomerulonephritis was admitted. Dyspnea appeared suddenly two
      days later. She received the diagnosis of acute lung injury according to the
      concept proposed by the American-European Consensus Conference. Management
      required corticosteroid pulse therapy and plasma exchange. This case is the first
      description of successful early and long-term management of severe lung
      involvement observed in cryoglobulinemia. Although she has been free of chest
      symptoms for seven months, further follow-up may be necessary to assess the
      potential danger of relapse.

PMID- 14714962
TI  - Two cases of endobronchial neurilemmoma and review of the literature in Japan.
AB  - Neurilemmomas are benign tumors which originate from Schwann cells. They rarely
      occur in the trachea or bronchus. We encountered two cases of endobronchial
      neurilemmoma and in this context, reviewed 48 cases previously reported in Japan.
      Neurilemmomas can occur in all regions of the bronchial tree and they often
      progress into both intraluminal and extraluminal spaces. Incomplete resection
      results in a local recurrence, despite being rare. As for appropriate therapies,
      surgery, bronchofiberoptic removal and yttrium aluminum garnet (YAG) laser
      resection can be chosen depending on the patient's status.

PMID- 14714963
TI  - Hericium erinaceum (yamabushitake) extract-induced acute respiratory distress
      syndrome monitored by serum surfactant proteins.
AB  - This is the first report suggesting a causal relationship between acute
      respiratory distress syndrome and Hericium erinaceum extract, which is
      commercialized as a diet food. A 63-year-old man was admitted to our hospital for
      intensive care of severe acute respiratory failure with diffuse infiltration in
      both lungs. Bronchoalveolar lavage fluid revealed a high percentage of
      lymphocytes. Lymphocyte stimulation test showed a strong reactivity against
      extract formulation of Hericium erinaceum (Yamabushitake), which he had taken
      four months before onset. He recovered with successful steroid pulse therapy
      under mechanical ventilation. Concentrations of surfactant protein (SP)-A and SP
      D in sera reflected the clinical features.

PMID- 14714964
TI  - Successful treatment of limited disease-small cell lung cancer with multimodality
      treatment consisting of concurrent chemoradiotherapy, high-dose chemotherapy with
      autologous peripheral blood stem cell transplantation and surgical resection.
AB  - A 65-year-old man with limited disease-small cell lung cancer was treated with
      concurrent chemoradiotherapy which resulted in a partial response. He further
      received high-dose chemotherapy with autologous peripheral blood stem cell
      transplantation. Development of non-small cell carcinoma was, however, suspected
      at a site of the residual nodule in cytological examination using bronchoscopy.
      He then underwent lobectomy, which revealed that the nodule was composed of
      necrotic tissue. He has been alive without recurrence for seven years. This
      multimodality treatment appeared to be effective for this patient. However,
      further investigation is necessary to clarify the role of multimodality
      treatment.

PMID- 14714965
TI  - Ischemic colitis as a manifestation of thrombotic microangiopathy following bone
      marrow transplantation.
AB  - Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by
      platelet aggregation and hemolytic anemia. In the setting of bone marrow
      transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate
      from acute graft-versus-host disease. We report a 32-year-old man who presented
      ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He
      suffered from treatment-resistant bloody diarrhea, and died of renal failure and
      Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries
      of arterioles and ischemic changes in the intestines and kidneys. Clinical and
      pathological characteristics of ischemic colitis due to BMT-associated TMA are
      described.

PMID- 14714966
TI  - Dermatomyositis with peripheral nervous system involvement: activation of
      vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in vasculitic
      lesions.
AB  - We describe two cases of dermatomyositis (DM) with nervous system involvement.
      Polyneuropathy was observed in both patients, and cerebral vasculitis was
      suspected in one patient. Histological examination of biopsied specimens of
      skeletal muscles, skin and sural nerves revealed vasculitis. Furthermore,
      vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) were
      overexpressed in vasculitic lesions. Although, VEGF and VEGFRs were not detected
      in biopsied specimens of skeletal muscle from normal subjects, they were observed
      in one of two patients with DM who did not exhibit neuropathy. These findings
      suggest the possibility that VEGF overproduction is associated with development
      of vasculitis in some cases of DM complicated with peripheral neuropathy.

PMID- 14714967
TI  - Predictive value of serial platelet count and VEGF determination for the
      management of DIC in the Crow-Fukase (POEMS) syndrome.
AB  - We report a case of a 62-year-old man diagnosed as Crow-Fukase syndrome (POEMS
      syndrome), in which the serial platelet count and vascular endothelial growth
      factor (VEGF) concentration were determined before and during the state of
      disseminated intravascular coagulation (DIC). The serum VEGF concentration was
      noted to be gradually decreased prior to DIC, after which it abruptly decreased
      with a corresponding drop in platelet count upon the onset of DIC. The
      physiological effects of VEGF are viewed as one of the causative factors in DIC
      and its abrupt and excessive release may have caused the exacerbation of the
      patient's clinical symptoms.

PMID- 14714968
TI  - Infectious endocarditis associated with subarachnoid hemorrhage, subdural
      hematoma and multiple brain abscesses.
AB  - Hemorrhagic stroke is a complication of infectious endocarditis (IE), and severe
      hemorrhage accompanies Staphylococcus aureus IE during early uncontrolled
      infection. However, subarachnoid hemorrhage (SAH) or subdural hematoma is rare. A
      case of S. aureus IE associated with SAH and subdural hematoma in the early stage
      is reported. A 54-year-old man with a history of mitral valve prolapse presented
      with fever. Two days after the onset, he fell into a confused state with
      convulsion and left hemiparesis. He became comatose and brain CT and MRI
      demonstrated SAH and subdural hematoma with severe right hemisphere swelling.
      Multiple brain abscesses were also observed. No septic aneurysm was detected by
      cerebral angiography.

PMID- 14714969
TI  - Severe pulmonary hypertension associated with primary Sjogren's syndrome.
AB  - Severe pulmonary hypertension is one of the fetal complications in various
      connective tissue diseases. We report a case of severe pulmonary hypertension
      associated with primary Sjogren's syndrome. In a lung biopsy specimen, there were
      findings of intimal and medial hypertrophy with narrowing vessel lumina and
      plexiform lesions. Moreover, deposits of immunoglobulin M, immunoglobulin A and
      complement protein C1q were found in the pulmonary arterial walls. Although
      pulmonary hypertension was refractory to oral prostacyclin, steroid therapy
      improved the clinical and hemodynamic conditions. In the present case, the
      immunological etiology may be related to the mechanisms of pulmonary hypertension
      associated with Sjogren's syndrome.

PMID- 14714970
TI  - Intractable skin necrosis and interstitial pneumonia in amyopathic
      dermatomyositis, successfully treated with cyclosporin A.
AB  - We report a patient with amyopathic dermatomyositis (DM) who mainly showed
      interstitial pneumonia and intractable skin necrosis in bilateral elbows and
      soles with a poor response to immunomediated therapy, including corticosteroid
      and high-dose intravenous immunoglobulin. Soon after starting oral cyclosporin A
      (CyA) the skin lesions healed completely and the interstitial pneumonia promptly
      improved in parallel with a decrease in serum KL-6. Since fatal interstitial
      pneumonia is frequently associated with amyopathic DM as in this case,
      administration of CyA should be actively considered as a therapeutic option when
      clinical symtoms are progressive and resistant to conventional treatments.

PMID- 14714971
TI  - Ursodeoxycholic acid therapy attenuated expression of adhesion molecule in
      primary biliary cirrhosis.

PMID- 14714972
TI  - Hemophagocytic syndrome, a possible association with aplastic anemia?

PMID- 14714973
TI  - Acute immune thrombocytopenic purpura in a 90-year-old woman treated with
      immunoglobulin as well as glucocorticoid.

PMID- 14714974
TI  - Meningioma in a woman receiving hormone therapy.

PMID- 14714975
TI  - Nonreactive miliary tuberculosis.

PMID- 14714976
TI  - On the representation of combinatorial libraries.

PMID- 14714977
TI  - From data to knowledge: chemical data management, data mining, and modeling in
      polymer science.

PMID- 14714978
TI  - A simple, inexpensive reactor with condenser for use in combinatorial chemistry.

PMID- 14714979
TI  - Construction and reactivity screening of a surface composition gradient for
      combinatorial discovery of electro-oxidation catalysts.

PMID- 14714980
TI  - Modular three-component solid-phase synthesis of unsymmetrical guanidines via
      resin capture of carbodiimides.

PMID- 14714981
TI  - Application of solution-phase parallel synthesis to preparation of trisubstituted
      1,2,4-triazoles.

PMID- 14714982
TI  - The synthesis of 3-substituted 6-aryl-3 H-benzo[a][1,2,3]triazinones using
      polymer-bound triazenes.

PMID- 14714983
TI  - 2D and 3D spatially addressed arrays for high-throughput automated synthesis of
      combinatorial libraries.
AB  - One of the key elements in the drug discovery process is the use of automation to
      synthesize libraries of compounds for biological screening. The "split-and-mix"
      approaches in combinatorial chemistry have been recognized as extremely powerful
      techniques to access large numbers of compounds, while requiring only few
      reaction steps. However, the need for effective encoding/deconvolution strategies
      and demands for larger amounts of compounds have somewhat limited the use of
      these techniques in the pharmaceutical industry. In this paper, we describe a
      concept of directed sort and combine synthesis with spatially arranged arrays of
      macroscopic supports. Such a concept attempts to balance the number of reaction
      steps, the confidence in compound identity, and the quantity of synthesized
      compounds. Using three-dimensional arrays of frames each containing a two
      dimensional array of macroscopic solid supports, we have conceptualized and
      developed a modular semiautomated system with a capacity of up to 100 000
      compounds per batch. Modularity of this system enables flexibility either to
      produce large diverse combinatorial libraries or to synthesize more focused
      smaller libraries, both as single compounds in 12-15 micromol quantities. This
      method using sortable and spatially addressed arrays is exemplified by the
      synthesis of a 15 360 compound library.

PMID- 14714984
TI  - Design of combinatorial shadow masks for complete ternary-phase diagramming of
      solid state materials.
AB  - We report on a novel mask design for the combinatorial synthesis of a ternary
      composition spreads library, which allows such libraries to be deposited through
      a series of simple masks on a rotatable mount. This eliminates the use of
      complicated actuation of a heated substrate. In our configuration, this design
      leads to a standard linear phase diagram by varying the growth rate of each
      constituent nearly linearly from 0 to 100% at a triangular area on the substrate.
      Film growth occurs as a series of cycles in which one molecular layer of the
      material is deposited over the entire area of the spread by a synchronization of
      the mask movement, target exchange, and laser pulses. The technique has been
      applied to the synthesis of photoluminescent TbCa(4)O(BO(3))(3)
      ScCa(4)O(BO(3))(3)-PrCa(4)O(BO(3))(3), demonstrating its value for the mapping of
      direct relationship between composition and the light-emitting property.

PMID- 14714985
TI  - Stereoselective diversity-oriented solution and solid-phase synthesis of
      tetrahydroquinoline-based polycyclic derivatives.
AB  - A diversity-oriented solution and solid-phase synthesis of tetrahydroquinoline
      based tricyclic derivatives has been achieved from enantiomerically pure, natural
      product-like bicyclic scaffold. The solution synthesis of enantiopure bicyclic
      scaffold was developed by asymmetric hetero Michael reaction. Our approach for
      the synthesis of polycyclic derivatives utilized regio- and stereoselective
      hetero Michael reaction and ring-closing metathesis as key steps in solution and
      on solid phase.

PMID- 14714986
TI  - A solid phase library synthesis of hydroxyindoline-derived tricyclic derivatives
      by Mitsunobu approach.
AB  - Hydroxyindoline-derived scaffold, 9, was synthesized with the goal of generating
      a library of indoline-based natural product-like tricyclic derivatives to be
      utilized as small-molecule chemical probes. The tricyclic ring was obtained by a
      Mitsunobu reaction of the N-nosyl amino acid conjugate with the primary hydroxyl
      group. The solid-phase synthesis was achieved by immobilizing scaffold 9 onto the
      solid support giving a compound, 15. This was then subjected to a series of
      reactions on solid phase, including the Mitsunobu reaction, leading to the
      desired indoline-derived tricyclic derivative. The final product has two
      diversity sites: (i) amino acid as the first diversity and (ii) amidation of the
      secondary amine for the second diversity. These two diversity sites were utilized
      in the library generation by IRORI split-and-mix approach.

PMID- 14714987
TI  - A solid-phase, library synthesis of natural-product-like derivatives from an
      enantiomerically pure tetrahydroquinoline scaffold.
AB  - With the goal of developing a library synthesis of tetrahydroquinoline-derived
      natural-product-like small molecules, a practical synthesis of enantiomerically
      pure tetrahydroquinoline scaffold was achieved. An asymmetric aminohydroxylation
      reaction was the key step in this strategy. This scaffold was further immobilized
      onto the solid support for the library generation. The library was obtained from
      three diversity sites: (i) acylation of the hydroxyl group (R(1)), (ii) coupling
      of the Fmoc-protected amino acid to the amino group (R(2)), and (iii) amidation
      of the N-terminal amine group (R(3)).

PMID- 14714988
TI  - Use of design of experiments to optimize high-throughput semipreparative LC and
      LC/MS methods.
AB  - This paper describes an investigation into decreasing the run time for high
      throughput semipreparative RP-HPLC methods without compromising the resolution.
      Experimental design was used to devise a small set of experiments in which
      factors, including solvent flow rate, solvent/column temperature, at-column
      dilution, and run time were varied systematically. The results were analyzed by
      means of multiple regression and partial least squares to generate a model
      relating the factors to the results, showing which factors are important. The
      model was then used to determine the optimal conditions.

PMID- 14714989
TI  - A traceless approach for the solid-phase synthesis of 6-amino-1,3,5-triazine-2,4
      diones.
AB  - A traceless approach for the solid-phase synthesis of 6-amino-1,3,5-triazine-2,4
      diones is described. Reaction of resin-bound S-methylisothiourea with isocyanates
      yielded resin-bound iminoureas 3, which reacted with amines to afford the
      corresponding guanidines 4. Following intramolecular cyclizative cleavage of the
      resin-bound guanidines using potassium ethoxide as a base, the desired products 5
      were obtained in good yields and high purities.

PMID- 14714990
TI  - Combinatorial synthesis of oxide powders with an autopipetting system.
AB  - We describe development of a relatively simple, rapid route to produce
      combinatorial compositional oxide powder libraries by autopipetting of liquid
      precursors. This partitioning approach should apply equally well to any low
      viscosity, liquid precursors for the synthesis of oxide powders. A commercial
      autopipet is modified by fitting a plastic "mask" assembly beneath the pipet
      array in order to partition and direct liquids into crucibles. A series of 10
      mixtures from two precursor solutions can be produced quickly. After they are
      dispensed, the liquid mixtures are dried in the crucibles and reacted at elevated
      temperatures to produce oxide powders. In the present work, the viability of the
      pipetting process is demonstrated by using a polymerizable complex powder
      synthesis method to produce (1-x) LaAlO(3) - x SrTiO(3) powders. For this system,
      a reaction at 900 degrees C for 2 h in air was sufficient to yield solid
      solutions in this system. X-ray powder diffraction was used to determine the
      pseudocubic unit cell lattice parameter. The linear change of lattice constant
      with composition confirms the compositional accuracy of the partitioning.

PMID- 14714991
TI  - Solid-phase synthesis of a library of hydroxyproline derivatives.
AB  - The synthesis of a library of N-alkylated O-arylated hydroxyproline derivatives
      has been achieved on solid phase. The choice of O-protection and the optimization
      of the Mitsunobu reaction involving a secondary alcohol were key to the success
      of this synthesis. First, acylation of resin-bound amines with N-Fmoc-O-THP
      hydroxyproline was accomplished readily. Subsequent deprotection of the Fmoc and
      reductive amination with different aldehydes resulted in the tertiary amine
      intermediate. The deprotection of the THP group by p-toluenesulfonic acid was
      followed by a Mitsunobu reaction with a series of phenols. Finally, the products
      were cleaved from the resin using trifluoroacetic acid to produce a 10 200 member
      library.

PMID- 14714992
TI  - Liquid-phase combinatorial synthesis of 1,4-benzodiazepine-2,5-diones as the
      candidates of endothelin receptor antagonism.
AB  - A library of 1,4-benzodiazepine-2,5-dione dicarboxylate derivatives containing
      aryl substituents at N(1)- and N(4)-positions to mimic the amino acid residues of
      Try-13, Phe-14, and Asp-18 in endothelin-1 is established by using the starting
      materials of alpha-amino esters, hydroxybenzaldehydes, nitrobenzoyl chlorides,
      and benzyl bromides in a polyethylene resin-bound liquid-phase synthesis. All of
      the six synthetic steps are conducted under mild conditions to give the desired
      products with reasonable yields and purity. The poly(ethylene glycol) support
      plays as a part of ester linkage that is released at the final step.

PMID- 14714993
TI  - A "catch and release" strategy for the parallel synthesis of 2,4,5-trisubstituted
      pyrimidines.
AB  - A resin capture and release strategy for making a combinatorial array of 2,4,5
      trisubstituted pyrimidines is demonstrated by capturing beta-ketoesters and beta
      ketoamides on a solid-supported piperazine. Through a cyclocondensation reaction,
      the solid-supported enaminone is reacted with several guanidines under heating or
      microwave irradiation affording the corresponding pyrimidines in good yield and
      chemical purity directly on solution. After this final step, the support can be
      effectively recycled.

PMID- 14714995
TI  - Carbonylation reaction of aryl halides on a polymer support using in situ
      generated carbon monoxide without the assistance of microwaves.
AB  - Palladium-catalyzed carbonylation, which was based on a ligand exchange reaction,
      efficiently converted immobilized aryl halides to amides under mild reaction
      conditions using molybdenum hexacarbonyl [Mo(CO)(6)] as the carbon monoxide
      source. The method easily operates without irradiating with microwaves and yields
      a wide range of highly pure amides after cleaving from the resin. The method
      could also be applied to the carbonylation of immobilized amines with aryl
      halides and to construct heterocyclic systems via a carbonylative cyclization.

PMID- 14714994
TI  - Synthesis and reactions of 7-fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3
      carboxylic acid: a novel scaffold for combinatorial synthesis of coumarins.
AB  - 7-Fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid has been
      prepared as a novel scaffold for combinatorial synthesis of coumarins. The
      scaffold has three points of diversity. The optimal conditions for its reactions
      with different nucleophiles in solid phase were obtained. Sixteen coumarin
      derivatives with different structures were designed and synthesized in solid
      phase to demonstrate its application as a scaffold for combinatorial synthesis of
      coumarins. Thirteen of these derivatives were obtained in high yields. Many of
      these model compounds fluoresce. Combinatorial libraries constructed with this
      novel scaffold may have interesting biological or physical properties.

PMID- 14714996
TI  - Identification of alpha-galactosyl epitope mimetics through rapid generation and
      screening of C-linked glycopeptide library.
AB  - A general methodology has been established for rapid generation and screening of
      combinatorial glycopeptide library and subsequent mass spectrometric sequencing
      to identify the mimetics of Galalpha(1,3)Gal epitopes. Using this approach,
      several active glycopeptide sequences were recognized and found to inhibit the
      binding of human natural anti-Gal antibodies with comparable IC(50)s to synthetic
      Galalpha(1,3)Gal oligosaccharides. The most active glycopeptides detected from
      the library included Gal-Tyr-Trp-Arg-Tyr, Gal-Thr-Trp-Arg-Tyr, and Gal-Arg-Trp
      Arg-Tyr. These glycopeptides showed higher affinities to anti-Gal antibodies than
      known Galalpha(1,3)Gal peptide mimetics, such as DAHWESWL and SSLRGF. Our results
      suggest that, by combining a peptide sequence (the "functional" mimic part) with
      a terminal alpha-linked galactose moiety (the "structural" mimic part), the
      resulting glycopeptide could be a very good Galalpha(1,3)Gal mimetic. Analysis of
      these active glycopeptides provided first-hand information regarding the binding
      site of anti-Gal antibodies to facilitate the structurally based design of more
      potent and stable inhibitors.

PMID- 14714997
TI  - Synthesis of a library of 3-oxopiperazinium and perhydro-3-oxo-1,4-diazepinium
      derivatives and identification of bioactive compounds.
AB  - The design and synthesis of a library of novel families of 3-oxopiperazinium and
      perhydro-3-oxo-1,4-diazepinium derivatives is reported. The library was composed
      of 44 3-oxopiperazinium derivatives (11 of these compounds had a spiranic
      skeleton) and 22 perhydro-3-oxo-1,4-diazepinium compounds. The synthetic
      procedure involved a 6-step sequence carried out in solution, along with the use
      of solid-phase linked scavengers and microwave activation for the rapid removal
      of the excess of amine reagents. A final cyclization step performed under mild
      conditions led to the charged heterocyclic moiety. Screening of this library in
      two biological assays identified active compounds that inhibit the activity of
      the vanilloid receptor TRPV1 and modulators of the multidrug resistance
      phenomenon. Thus, this synthetic sequence represents a facile and convenient
      entry to unprecedented libraries of this sort of tetraalkylammonium derivatives
      that may be of use for identification of novel scaffolds of diverse biological
      activity.

PMID- 14714998
TI  - Solid-phase synthesis of an isoxazolinopyrrole library.
AB  - A four-step solid-phase synthesis of isoxazolinopyrroles 8 that employs an acid
      labile 2-(4-formyl-3-methoxyphenoxy)ethyl polystyrene HL resin 1 is reported.
      Resin-bound vinyl sulfone 5 is obtained by DIC coupling with acid 4, which was in
      turn synthesized in solution phase by a regioselective nitrile oxide 1,3-dipolar
      cycloaddition. The resin-bound pyrrole 7 was synthesized on solid phase by
      pyrrole annulation with various isocyano derivatives and potassium t-butoxide in
      which the sulfone alpha-anion generated by Michael addition gives the desired
      pyrrole through internal condensation followed by a sigmatropic [1,5]-hydrogen
      shift. The resulting isoxazolinopyrroles 8 were released from resin 7 by 10% TFA
      in moderate to excellent overall yields from 2-(4-formyl-3-methoxyphenoxy)ethyl
      polystyrene HL resin 1.

PMID- 14714999
TI  - Combinatorial electrochemical screening of fuel cell electrocatalysts.
AB  - Combinatorial methods have been applied to the preparation and screening of fuel
      cell electrocatalysts. Hardware and software have been developed for fast
      sequential measurements of cyclic voltammetric and steady-state currents in 64
      element half-cell arrays. The arrays were designed for the screening of high
      surface-area supported electrocatalysts. Analysis software developed allowed the
      semiautomated processing of the large quantities of data, applying filters that
      defined figures of merit relevant to fuel cell catalyst activity and tolerance.
      Results are presented on the screening of carbon-supported platinum catalysts of
      varying platinum metal loading on carbon (and thus, particle size) in order to
      demonstrate the speed and sensitivity of the screening methodology. CO electro
      oxidation, oxygen reduction, and methanol oxidation on a series of such catalysts
      reveal clear trends in characteristics and activities. Catalysts with smaller
      particle sizes reveal structure in the CO stripping voltammetry that can be
      associated with edge sites in addition to the closely packed planes, and this is
      concomitantly reduced as particle size is increased. Specific activity for steady
      state methanol oxidation and oxygen reduction at room temperature in H(2)SO(4)
      electrolyte is found to be a maximum for the largest particle sizes, in agreement
      with the literature. These trends in activity are significantly smaller than the
      differences in activities of promoted platinum-based alloy catalysts for the same
      reaction.

PMID- 14715000
TI  - Horseradish peroxidase-catalyzed polymerization of cardanol in the presence of
      redox mediators.
AB  - Horseradish peroxidase-catalyzed polymerization of cardanol in aqueous organic
      solvent was investigated in the presence of a redox mediator. Cardanol is a
      phenol derivative from a renewable resource mainly having a C15 unsaturated
      hydrocarbon chain with mostly 1-3 double bonds at a meta position. Unlike soybean
      peroxidase (SBP), it has been shown that horseradish peroxidase (HRP) is not able
      to perform oxidative polymerization of phenol derivatives having a bulky meta
      substituent such as cardanol. For the first time, redox mediators have been
      applied to enable horseradish peroxidase to polymerize cardanol. Veratryl
      alcohol, N-ethyl phenothiazine, and phenothiazine-10-propionic acid were tested
      as a mediator. It is surprising that the horseradish peroxidase-catalyzed
      polymerization of cardanol took place in the presence of N-ethyl phenothiazine or
      phenothiazine-10-propionic acid. However, veratryl alcohol showed no effect. FT
      IR and GPC analysis of the product revealed that the structure and properties of
      polycardanol formed by HRP with a mediator were similar to those by SBP. This is
      the first work to apply a redox mediator to enzyme-catalyzed oxidative
      polymerization. Our new finding that oxidative polymerization of a poor
      substrate, which the enzyme is not active with, can take place in the presence of
      an appropriate mediator will present more opportunities for the application of
      enzyme-catalyzed polymerization.

PMID- 14715001
TI  - Thermally cross-linked oligo(poly(ethylene glycol) fumarate) hydrogels support
      osteogenic differentiation of encapsulated marrow stromal cells in vitro.
AB  - A novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF), cross-linked with a
      thermal radical initiation system has recently been developed in our laboratory
      as an injectable, biodegradable cell carrier for regeneration of orthopaedic
      tissues. The cross-linking, swelling, and degradative properties of hydrogels
      prepared from OPF with poly(ethylene glycol) of two different chain lengths were
      assessed. The two OPF types had similar gelation onset times ( approximately 3.6
      min) but, when cross-linked for 8 min at 37 degrees C, exhibited significantly
      different swelling characteristics (fold swelling: 17.5 +/- 0.2 vs 13.4 +/- 0.4).
      Rat marrow stromal cells (MSCs) were then directly combined with the hydrogel
      precursors and encapsulated in a model OPF formulation at approximately 14
      million cells/mL, cultured in vitro in the presence of osteogenic supplements
      (dexamethasone), and monitored over 28 days via histology. MSC differentiation in
      these samples (6 mm diameter x 0.5 mm thick before swelling), as determined by
      Von Kossa staining for calcified matrix, was apparent by day 21. At day 28,
      mineralized matrix could be seen throughout the samples, many microns away from
      the cells. These experiments strongly support the usefulness of thermally cross
      linked OPF hydrogels as injectable cell carriers for bone regeneration.

PMID- 14715002
TI  - Hydrolytic and enzymatic degradation of liquid-crystalline aromatic/aliphatic
      copolyesters.
AB  - Aromatic/aliphatic copolyesters containing hydrophilic moieties in the main chain
      or side chain were synthesized by bulk polycondensation of aromatic monomers
      without or with solubilizing substituents and aliphatic monomers. Hydrolytic and
      enzymatic degradation studies were carried out in vitro at 37 degrees C in pH 7.4
      phosphate buffer and in Tris-HCl buffer containing proteinase K. The results
      indicate that liquid-crystalline aromatic/aliphatic copolyesters are degradable
      hydrolytically as well as enzymatically. The change in composition and morphology
      of the polyester films were monitored by nuclear magnetic resonance and scanning
      electron microscopy. The results suggested that aromatic species and aliphatic
      moieties could be released into aqueous solution during hydrolytic degradation of
      aromatic/aliphatic copolyesters with ethyleneoxy groups on the side chain.
      Modifying aromatic species with hydrophilic groups in aromatic/aliphatic
      copolyesters was an efficient method to improve degradability and
      biocompatibility due to improved solubility of degradation products in aqueous
      solution. Mechanical tests indicated that the copolyesters exhibited good
      mechanical properties prior to degradation, which can be of relevance for bone
      tissue engineering.

PMID- 14715003
TI  - Immobilization of lipase on chitin and its use in nonconventional biocatalysis.
AB  - Chitin was functionalized with hexamethylenediamine followed by glutaraldehyde
      activation, and its capacity to bind Candida rugosa lipase was investigated. The
      loading of 250 units g(-1) support showed to be effective, resulting in a uniform
      enzyme fixation with high catalytic activity. Both free and immobilized lipases
      were characterized by determining the activity profile as a function of pH,
      temperature, and thermal stability. For the immobilized lipase, the influence of
      the reaction temperature and substrate polarity in nonconventional biocatalysis
      was also analyzed. Production of butyl esters was found to be dependent on the
      substrate partition coefficient, which accounts the greatest value for the system
      butanol and butyric acid. The highest enzyme activity was found for the system
      butanol and caprylic acid at a reaction temperature of 40 degrees C. Under such
      conditions, the operational stability tests indicated that a small enzyme
      deactivation occurs after 12 batches, revealing a biocatalyst half-life of 426.7
      h.

PMID- 14715004
TI  - Poly(N,N,N-trimethylammoniumalkyl acrylamide chloride) based hydrogels for serum
      cholesterol reduction.
AB  - Hydrogels present an attractive alternative to nanoscale block copolymer
      aggregates and microscale resin beads as potential asystemic serum cholesterol
      reduction materials. Not only would the oral delivery of these materials be more
      pleasant than the sand-like bile salt anion sequestrant beads but also the
      hydrogel preparation is much simpler than the copolymer aggregate analogues
      [Cameron, N. S.; Eisenberg, A.; Brown, G. R. Biomacromolecules 2002, 3, 116-123.
      Cameron, N. S.; Eisenberg, A.; Brown, G. R. Biomacromolecules 2002, 3, 124-132].
      Our goal was to explore these materials building on our experience with bulk
      resins and self-assembled copolymers. In this paper, following a brief
      introduction to hydrogels and their application to hypercholesterolemia, the
      synthesis, characterization, and preliminary glycocholate binding properties of
      poly(N,N,N-trimethylammoniumalkyl acrylamide chloride)gel are presented [Cameron,
      N. S.; Eisenberg, A.; Brown, G. R. Polym. Preprints 2002, 43, 771-772].

PMID- 14715005
TI  - Endosomal escape of polymeric gene delivery complexes is not always enhanced by
      polymers buffering at low pH.
AB  - One of the crucial steps in gene delivery with cationic polymers is the escape of
      the polymer/DNA complexes ("polyplexes") from the endosome. A possible way to
      enhance endosomal escape is the use of cationic polymers with a pKa around or
      slightly below physiological pH ("proton sponge"). We synthesized a new polymer
      with two tertiary amine groups in each monomeric unit [poly(2-methyl-acrylic acid
      2-[(2-(dimethylamino)-ethyl)-methyl-amino]-ethyl ester), abbreviated as pDAMA].
      One pKa of the monomer is approximately 9, providing cationic charge at
      physiological pH, and thus DNA binding properties, the other is approximately 5
      and provides endosomal buffering capacity. Using dynamic light scattering and
      zeta potential measurements, it was shown that pDAMA is able to condense DNA in
      small particles with a surface charge depending on the polymer/DNA ratio. pDAMA
      has a substantial lower toxicity than other polymeric transfectants, but in
      vitro, the transfection activity of the pDAMA-based polyplexes was very low. The
      addition of a membrane disruptive peptide to pDAMA-based polyplexes considerably
      increased the transfection efficiency without adversely affecting the
      cytotoxicity of the system. This indicates that the pDAMA-based polyplexes alone
      are not able to mediate escape from the endosomes via the proton sponge
      mechanism. Our observations imply that the proton sponge hypothesis is not
      generally applicable for polymers with buffering capacity at low pH and gives
      rise to a reconsideration of this hypothesis.

PMID- 14715006
TI  - Poly(hydroxyalkanoic acid) Biosynthesis in Ectothiorhodospirashaposhnikovii:
      Characterization and Reactivity of a Type III PHA Synthase.
AB  - Ectothiorhodospira shaposhnikovii is able to accumulate polyhydroxybutyrate (PHB)
      photoautotrophically during nitrogen-limited growth. The activity of
      polyhydroxyalkanoate (PHA) synthase in the cells correlates with PHB
      accumulation. PHA synthase samples collected during the light period do not show
      a lag phase during in vitro polymerization. Synthase samples collected in the
      dark period displays a significant lag phase during in vitro polymerization. The
      lag phase can be eliminated by reacting the PHA synthase with the monomer, 3
      hydroxybutyryl-CoA (3HBCoA). The PHA synthase genes (phaC and phaE) were cloned
      by screening a genomic library for PHA accumulation in E. coli cells. The PHA
      synthase expressed in the recombinant E. coli cells was purified to homogeneity.
      Both sequence analysis and biochemical studies indicated that this PHA synthase
      consists of two subunits, PhaE and PhaC and, therefore, belongs to the type III
      PHA synthases. Two major complexes were identified in preparations of purified
      PHA synthase. The large complex appears to be composed of 12 PhaC subunits and 12
      PhaE subunits (dodecamer), whereas the small complex appears to be composed of 6
      PhaC and 6 PhaE subunits (hexamer). In dilute aqueous solution, the synthase is
      predominantly composed of hexamer and has low activity accompanied with a
      significant lag period at the initial stage of reaction. The percentage of
      dodecameric complex increases with increasing salt concentration. The dodecameric
      complex has a greatly increased specific activity for the polymerization of
      3HBCoA and a negligible lag period. The results from in vitro polymerizations of
      3HBCoA suggest that the PHA synthase from E. shaposhnikovii may catalyze a living
      polymerization and demonstrate that two PhaC and two PhaE subunits comprise a
      single catalytic site in the synthase complex.

PMID- 14715007
TI  - DNA hybridization in nanostructural molecular assemblies enables detection of
      gene mutations without a fluorescent probe.
AB  - We have developed a simple single nucleotide polymorphisms (SNPs) analysis
      utilizing DNA hybridization in nanostructural molecular assemblies. The novel
      technique enables the detection of a single-base mismatch in a DNA sequence
      without a fluorescent probe. This report describes for the first time that DNA
      hybridization occurs in the nanostructural molecular assemblies (termed reverse
      micelles) formed in an organic medium. The restricted nanospace in the reverse
      micelles amplifies the differences in the hybridization rate between mismatched
      and perfectly matched DNA probes. For a model system, we hybridized a 20-mer
      based on the p53 gene sequence to 20-mer complementary oligonucleotides with
      various types of mismatches. Without any DNA labeling or electrochemical
      apparatus, we successfully detected the various oligonucleotide mismatches by
      simply measuring the UV absorbance at 260 nm.

PMID- 14715008
TI  - Conformation and structure of polymeric contrast agents for medical imaging.
AB  - The structure of Gd-DTPA-polylysine, Gd-DOTA-polylysine, Gd-SCN-Bz-DOTA
      polylysine, and Gd-DTPA-poly(glu:lys) was investigated with circular dichroism,
      gel permeation chromatography, low angle light scattering, and proton
      longitudinal relaxivity. Molecular modeling calculations were performed and
      predicted helical secondary structure for charged Gd-chelator residues, i.e., Gd
      DTPA, when the DTPA conjugation levels reached 90% and higher. This helical
      secondary structure was observed with circular dichroism. The conformational
      transition from coiled to extended linear was observed also by gel permeation
      chromatography and by proton relaxivity measurements. The helical secondary
      structure was not observed when the chelator was changed to DOTA. The residue
      charge interactions were eliminated in this case since the Gd-DOTA complex had no
      net charge. For this construct, the gel permeation and relaxivity measurements
      indicated a coiled conformation. An extended linear conformation was regained
      when the chelator complex was changed to Gd-SCN-Bz-DOTA, which had a net negative
      charge. The functional aspects of these structures were investigated by MR
      imaging of an animal tumor model. The linear extended polymer constructs gave 10
      fold higher tumor signals then the coiled-collapsed constructs, indicating a much
      higher degree of trans-endothelial transport in the tumors.

PMID- 14715009
TI  - Mild, solvent-free omega-hydroxy acid polycondensations catalyzed by candida
      antarctica lipase B.
AB  - Immobilized Candida antarctica Lipase B (Novozyme-435) was studied for bulk
      polyesterifications of linear aliphatic hydroxyacids of variable chain length.
      The products formed were not fractionated by precipitation. The relative
      reactivity of the hydroxyacids was l6-hydroxyhexadecanoic acid approximately 12
      hydroxydodecanoic acid approximately 10-hydroxydecanoic acid (DPavg congruent
      with 120, Mw/Mn <or = 1.5, 48 h, 90 degrees C) > 6-hydroxyhexanoic acid (DPavg
      congruent with 80, Mw/Mn < or = 1.5, 48 h, 90 degrees C). Remarkable improvements
      in molecular-weight buildup resulted from leaving water in the reaction. By 4 h,
      without application of vacuum, the DPavg for 12- and 16-carbon hydroxyacids was
      about 90. In contrast, with identical substrates and water removal, the DPavg at
      4 h was about 23. Large differences in the molecular-weight build up of 12
      hydroxydodecanoic acid were observed for catalyst concentrations (%-by-wt
      relative to monomer) of 0.1, 0.5, 1, and 10. Nevertheless, by 24 h, with 1%
      catalyst containing 0.1% lipase, poly(12-hydroxydodecanoic acid) with Mn 17 600
      was formed. For 12-hydroxydodecanoic acid polymerization at 90 degrees C, the
      catalyst activity decreased by 7, 18, and 25% at reaction times of 4, 24, and 48
      h, respectively. Furthermore, the retention of catalyst activity was invariable
      as a function of the substrates used.

PMID- 14715010
TI  - Nanogel formation consisting of DNA and poly(amido amine) dendrimer studied by
      static light scattering and atomic force microscopy.
AB  - Binding of a poly(amido amine) dendrimer with salmon testes DNA in an aqueous
      solution of 0.01 M NaCl at pH 6.5 has been investigated. It was shown from the
      physicochemical experiments of static light scattering and ultra-violet and
      circular dichroism spectroscopy that at a 0.2 mixing ratio of dendrimer/DNA
      (number ratio of NH2 groups in dendrimer vs phosphate groups in DNA) significant
      conformational change of the DNA occurred owing to the binding of dendrimers on
      the DNA chain. The dendrimer/DNA complexes formed aggregates (nanogels) when the
      mixing ratio was increased above 0.2. Weight-averaged molecular weight, radius of
      gyration, and turbidity measurements revealed that the size of the aggregates
      increased up to a mixing ratio of 0.8. Atomic force microscopic images certified
      the formation of complexes and the morphology of the nanogels.

PMID- 14715011
TI  - Synthesis, characterization, and mesophase formation of phenylacetoxy cellulose
      and its halogenated derivatives.
AB  - A series of phenylacetoxy cellulosics with degrees of substitution (DS) between
      1.4 and 3.0 and different halogenation (2-chloro, 3-chloro, 4-chloro, 2,4
      dichloro, 3,4-dichloro, and 4-bromo) were synthesized. All the prepared
      phenylacetoxy cellulosics were soluble in dimethylformamide (DMF) and DMAc. The
      solubility increased with increasing DS. Mesophases were observed for all of the
      phenylacetoxy cellulosics with low to medium DS (DS < 2.5) in DMF and DMAc. Non-
      or mono-halogeneated phenylacetoxy cellulosics with high DS (DS > 1.9) were
      soluble in methylene chloride (CH2Cl2), whereas those with very low DS or di
      halogenation on the phenyl ring were only slightly swollen or partially soluble
      in CH2Cl2. Non- and mono-halogenated phenylacetoxy cellulosics were soluble in
      DMSO and formed liquid crystals regardless of the DS, in contrast to CH2Cl2
      solutions which display liquid crystalline behavior at medium to high DS (DS >
      1.9) only. The solubility of the di-halogenated phenylacetoxy cellulosics in DMSO
      was limited to approximately 40 wt %.

PMID- 14715012
TI  - Self-assembly and dynamics of poly(gamma-benzyl-l-glutamate) peptides.
AB  - The structure and the associated dynamics have been investigated in a series of
      oligopeptides of gamma-benzyl-l-glutamate using DSC, WAXS, FTIR, NMR and
      dielectric spectroscopy, and rheology, respectively. The peptides with degrees of
      polymerization below 18 are mixtures of a lamellar assembly of beta sheets and of
      columnar hexagonal arrangement of alpha helices, whereas for longer chains, the
      intramolecular hydrogen bonds stabilize only the alpha-helical conformations.
      Multiple dielectrically active processes were found. Starting from low
      temperatures, the two Arrhenius processes (gamma and beta), with apparent
      activation energies of 20.6 and 50.2 kJ/mol, respectively, associate with the
      local relaxation of the side-chain methylene units (gamma process) and with more
      cooperative motions of the side chain dipoles sensitive to the 7/2 helical
      packing (beta process). The glass transition is manifested in the thermal
      properties with a step in the heat capacity and with an intense dielectric
      process bearing characteristics (molecular weight dependence, temperature
      dependence of relaxation times) known from amorphous polymers. Based on these
      findings, the alpha process is attributed to the relaxation of amorphous segments
      located between and at the end of helically ordered segments. Two slower
      processes were identified with opposite molecular weight dependence. The weak
      intermediate mode with an M2 molecular weight dependence of the characteristic
      relaxation times suggests amorphous-like chains, whereas the strong slower
      process originates from the loss of dipole orientational capacity caused by
      structural defects and reflects the migration of helical sequences along the
      chains. This identifies the helices as structures extending over rather short
      fragments of chains (i.e., of low persistence length). The viscoelastic response
      indicated that the structural defects arise from locally aggregated chains that
      inhibit the flow of oligopeptides.

PMID- 14715013
TI  - Cellulose derivative-hyaluronic acid-based microporous hydrogels cross-linked
      through divinyl sulfone (DVS) to modulate equilibrium sorption capacity and
      network stability.
AB  - The aim of this work is to obtain a chemically cross-linked hydrogel from
      hyaluronic acid and cellulose derivatives that exhibits sensitivity to variation
      of the composition of the external absorbing medium and an equilibrium sorption
      capacity higher than a common hyaluronic acid-based hydrogel, in view of its
      potential use in prevention of postsurgical soft tissue adhesion. This has been
      achieved by chemical stabilization of hyaluronic acid (HA) and cellulose
      derivatives, hydroxyethylcellulose (HEC) and carboxymethylcellulose (CMCNa)
      through the difunctional cross-linker divinyl sulfone. Significant increase in
      sorption capacity, both in water and in water solutions at different ionic
      strength, has been observed for these samples in comparison with hydrogels
      obtained through chemical stabilization of hyaluronic acid. Moreover, different
      dehydration procedures adopted for the xerogel synthesis have been used, which
      resulted in a modulation of the equilibrium sorption capacity. Hyaluronic acid
      stability has been confirmed by means of NMR analysis.

PMID- 14715014
TI  - Size and structure characterization of ethylhydroxyethyl cellulose by the
      combination of field-flow fractionation with other techniques. Investigation of
      ultralarge components.
AB  - Ethylhydroxyethyl cellulose (EHEC) of three different viscosity classes (EHEC I,
      II, and III) was analyzed by programmed cross-flow asymmetrical flow field-flow
      fractionation coupled to multiangle light scattering and refractive index
      detectors to determine their size and molar mass distribution. Two size
      populations were detected in the two lower viscosity classes, EHEC I and II, one
      high molar mass and one ultrahigh molar mass (UHM). The two covered molar masses
      from 10(4) up to 10(9) g X mol(-1). The highest viscosity class EHEC III was less
      size-dispersed covering molar masses from 5 x 10(5) to 5 x 10(7) g.mol(-1).
      Filtering of the EHEC II solution removed small amounts of compact UHM material.
      Enzyme treatments were performed on EHEC II to further characterize it. Matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and anion
      ion-exchange chromatography coupled to pulsed amperometric detection showed that
      the UHM component contained EHEC.

PMID- 14715015
TI  - Polyester coating of cellulose fiber surfaces catalyzed by a cellulose-binding
      module-Candida antarctica lipase B fusion protein.
AB  - A new approach to introduce polymers to cellulosic materials was developed by
      using the ability of a cellulose-binding module-Candida antarctica lipase B
      conjugate to catalyze ring-opening polymerization of epsilon-caprolactone in
      close proximity to cellulose fiber surfaces. The epsilon-caprolactone was
      introduced to the cellulose surfaces either by simple addition of liquid monomer
      or through gas phase. The effects of water activity and temperature on the lipase
      catalyzed polymerization process were investigated. Analysis showed that the
      water content in the system primarily regulated the obtained polymer molecular
      weight, whereas the temperature influenced the reaction rate. The hydrophobicity
      of the obtained surfaces did not arise from covalent attachment of the
      poly(epsilon-caprolactone) to the surface hydroxyl groups but rather from surface
      deposited polymers which could be readily extracted. The degree of lipase
      catalyzed hydrolysis through introduction of water to the polymer-coated
      cellulose fiber surfaces was also investigated and shown to be significant.

PMID- 14715016
TI  - Amplification of antioxidant activity of catechin by polycondensation with
      acetaldehyde.
AB  - Catechin exhibits numerous biological and pharmacological effects attributed to
      antioxidant action. The synthetic poly(catechin)s condensed through acetaldehyde
      with different molecular weights were assessed in terms of antioxidant activity
      and enzyme inhibitory activity on the basis of a catechin repeating unit and
      compared with monomeric catechin. The poly(catechin)s showed great amplification
      of superoxide scavenging activity, xanthine oxidase (XO) inhibitory activity, and
      inhibition effects on human low-density lipoprotein oxidation initiated by 2,2'
      azobis(2-amidinopropane)dihydrochloride (AAPH) as a radical generator on the
      catechin unit level, compared to monomeric catechin: these activities were
      proportional to their molecular weights. The reducing power of the polymer was
      lower than that of monomeric catechin, which decreased with increasing the
      molecular weight. The polymer also protected endothelial cells from oxidative
      injury induced by AAPH, with a greater effect expressed on a catechin unit basis
      than that of the monomer. These results demonstrate that the poly(catechin)s are
      more potent antioxidant agents and enzyme inhibitors.

PMID- 14715017
TI  - Origin of the limited alpha-amylolysis of debranched maltodextrins crystallized
      in the A form: a TEM study on model substrates.
AB  - The detailed ultrastructure of a new type of resistant starch and the way that it
      is modified during hydrolysis by alpha-amylases were studied by transmission
      electron microscopy (TEM) on model starch crystals. The selected substrates were
      waxy maize starch lintners and A-type crystals prepared from low degree of
      polymerization (DP) amylose. A model describing the stacking of double helices is
      proposed for A-type low DP amylose crystals. The enzymatic hydrolysis of both
      lintners and low DP crystals has been shown to occur by the side of double
      helices and not their ends. The results were transposed to a new type of
      resistant starch (RS) produced by debranching maltodextrins in concentrated
      solutions. This product presents A-type crystallinity contrary to all other known
      classified RS. Moreover it consists of low DP chains similar to the model
      crystals studied and yields similar electron diffraction patterns to those of A
      type low DP crystals. The similarities in the morphology of these substrates with
      that of the studied RS led us to attribute its resistance to its particularly
      dense and compact morphology, resulting from the epitaxial growth of elementary
      crystalline A-type platelets. In the resulting structure, the accessibility of
      double helices to alpha-amylase is strongly reduced by aggregation.

PMID- 14715018
TI  - A gel network constituted by rigid schizophyllan chains and nonpermanent cross
      links.
AB  - This work reports a gel network formed by rigid schizophyllan (SPG) chains with
      Borax as a cross-linking agent. The formed cross-links are non-permanent and
      somewhat dynamic in nature because the cross-linking reaction is governed by a
      complexation equilibrium. Gelation processes are traced by dynamic viscoelastic
      measurements to examine the effects of Borax content, SPG concentration,
      temperature, salt concentration, salt type, and strain. The first-order kinetic
      model containing three parameters, t(0) (induction time), 1/tau(c) (gelation
      rate), and (saturated storage modulus), is successfully applied to describe the
      gelation of the SPG-Borax system. Gelation occurs faster at higher Borax content,
      higher SPG concentration, higher salt concentration, or lower temperature.
      Moreover the gelation is cation-type-specific. Storage modulus is a linear
      function of both Borax content and SPG concentration. The linear relationship
      between storage modulus and Borax content can be explained by a modified ideal
      rubber elasticity theory with a front factor alpha to take into account the
      presence of ineffective cross-links and the effect of SPG chain rigidity. On the
      other hand, the linear dependence of storage modulus on SPG concentration could
      be explained on the basis of chain-chain contacting behavior of extended SPG
      chains. Apparent activation energy and cross-linking enthalpy are calculated to
      be -74.5 and -32.4 kJ/mol for the present system. Strain sweep measurements
      manifest that the elasticity behavior of this gel starts to deviate from Gaussian
      chain network at a small strain of 10%.

PMID- 14715019
TI  - Investigation of the degradation mechanisms of poly(malic acid) esters in vitro
      and their related cytotoxicities on J774 macrophages.
AB  - Poly(beta-malic acid) hydrophobic derivatives are promising polymers for
      biomedical and pharmaceutical applications. The objectives of the present work
      were to study the in vitro degradation profile of three PMLA hydrophobic
      derivatives and to evaluate their cytotoxicity before and after degradation. For
      this purpose, nanoparticles from poly(benzyl-malate) (PMLABe), poly(hexyl-malate)
      (PMLAHe), and poly(malic acid-co-benzyl-malate) (PMLAH/He) were prepared for
      degradation studies on standardized materials. Size exclusion chromatography
      (SEC) and 1H NMR indicated that degradation occurred by random hydrolysis of the
      polymer main chain for all three polymer derivatives. The presence of carboxyl
      groups on the side chain and their esterification with different alcohols varying
      hydrophilicities could affect the degradation rate. It was postulated that the
      degradation depended on the rate of diffusion of water into the core of the
      particles. The cytotoxicity of the polymer nanospheres as well as their
      degradation products were evaluated in vitro with J774 A1 murine macrophage-like
      cell line. The cytotoxicity depended on the degradation rate of the polymers and
      the amount of degradation products of low molecular weight produced.

PMID- 14715020
TI  - Comblike complexes of bacterial poly(gamma,d-glutamic acid) and cationic
      surfactants.
AB  - The ability of microbally produced poly(gamma,d-glutamic acid) to form stable
      polyelectrolyte-opposite charged surfactant complexes was investigated. A
      sonicated sample of polyacid with a molecular weight about 10(5) Da and a content
      of d enantiomer higher than 90% was used in this study. Nearly stoichiometric
      complexes of poly(gamma,d-glutamate) anions and alkyltrimethylammonium cations
      bearing linear alkyl chains with even numbers of carbon atoms from 12 up to 22
      were "synthesized" by precipitation from equimolar mixtures of aqueous solutions
      of the two components. All complexes were found to adopt stratified
      supramolecular structures made of alternating layers of poly(gamma,d-glutamate)
      and surfactant with a periodicity increasing from 3.2 up to 4.3 nm according to
      the length of the alkyl side chain. No definite evidence indicative of the
      conformation adopted by the main chain in these complexes could be afforded. In
      all cases, the alkyl chains are in an extended conformation and oriented normal
      or nearly normal to the layer planes. Polymethylene chains with more than 16
      carbon atoms were partially crystallized in the complexes in a separated
      paraffinic phase, whereas no crystallinity was detected for shorter lengths. The
      crystallized paraffinic phases were found to melt reversibly at temperatures
      between 40 and 70 degrees C. This process was found to happen with a concomitant
      expansion-contraction that amounts between 2 and 8% of the long period of the
      structure but without significant alteration of the layered arrangement.

PMID- 14715021
TI  - Isolation and characterization of gram-positive cyanophycin-degrading bacteria
      kinetic studies on cyanophycin depolymerase activity in aerobic bacteria.
AB  - This study is the first report on the extracellular degradation of cyanophycin
      (CGP) by Gram-positive bacteria. Three different Gram-positive bacteria were
      isolated from forest soil that were able to utilize CGP as the sole carbon source
      for growth. The isolates were assigned to species of the genera Bacillus and
      Micromonospora. From one of the isolates, which was taxonomically affiliated as
      Bacillus megaterium strain BAC19, the extracellular CGP depolymerase
      (extracellular CGPase; CphEBm) was purified to electrophoretic homogeneity by
      fast protein liquid chromatography and affinity binding to an arginine-agarose
      column. The purified enzyme was specific for hydrolytic cleavage of CGP, and
      inhibitor studies indicated that CphEBm is a serine-type peptidase. As CGP
      degradation products, (beta-Asp-Arg)2 tetrapeptides in addition to beta-Asp-Arg
      dipeptides occurred, which were identified by electrospray ionization mass
      spectrometry analysis. Furthermore, a novel quantitative enzyme assay was
      developed for kinetic studies on CGP depolymerases. For CphEBm, as well as for
      the extracellular CGPase of Pseudomonas anguilliseptica strain BI (CphEPa), KM
      values of 2.2 and 1.0 microM, respectively, for CGP were determined.

PMID- 14715022
TI  - Novel chitosan-based films cross-linked by genipin with improved physical
      properties.
AB  - Novel cross-linked chitosan-based films were prepared using the solution casting
      technique. A naturally occurring and nontoxic cross-linking agent, genipin, was
      used to form the chitosan and chitosan/poly(ethylene oxide) (PEO) blend networks,
      where two types of PEO were used, one with a molecular weight of 20 000 g/mol
      (HPEO) and the other of 600 g/mol (LPEO). Genipin is used in traditional Chinese
      medicine and extracted from gardenia fruit. Importantly, it overcomes the problem
      of physiological toxicity inherent in the use of some common synthetic chemicals
      as cross-linking agents. The mechanical properties and the stability in water of
      cross-linked and un-crosslinked chitosan and chitosan/PEO blend films were
      investigated. It was shown that, compared to the transparent yellow, un-cross
      linked chitosan/PEO blend films, the genipin-cross-linked chitosan-based film,
      blue in color, was more elastic, was more stable, and had better mechanical
      properties. Genipin-cross-linking produced chitosan networks that were insoluble
      in acidic and alkaline solutions but were able to swell in these aqueous media.
      The swelling characteristics of the films exhibit sensitivity to the
      environmental pH and temperature. The surface properties of the films were also
      examined by contact angle measurements using water and mixtures of water/ethanol.
      The results showed that, with the one exception of cross-linked pure chitosan in
      100% water, the cross-linked chitosan and chitosan/PEO blends were more
      hydrophobic than un-crosslinked ones.

PMID- 14715023
TI  - Improved synthesis with high yield and increased molecular weight of
      poly(alpha,beta-malic acid) by direct polycondensation.
AB  - The development of synthetic biodegradable polymers, such as poly(alpha-hydroxy
      acid), is particularly important for constructing medical devices, including
      scaffolds and sutures, and has attracted growing interest in the biomedical
      field. Here, we report a novel approach to preparing high molecular weight
      poly(malic acid) (HMW--PMA) as a biodegradable and bioabsorbable water-soluble
      polymer. We investigated in detail the reaction conditions for the simple direct
      polycondensation of l-malic acid, including the reaction times, temperatures, and
      catalysts. The molecular weight of synthesized alpha,beta-PMA is dependent on
      both the reaction temperature and time. The optimum reaction condition to obtain
      alpha,beta-PMA by direct polycondensation using tin(II) chloride as a catalyst
      was thus determined to be 110 degrees C for 45 h with a molecular weight of 5300.
      The method for alpha,beta-PMA synthesis established here will facilitate
      production of alpha,beta-PMA of various molecular weights, which may have a
      potential utility as biomaterials.

PMID- 14715024
TI  - Effect of degree of acetylation on gelation of konjac glucomannan.
AB  - Effect of the degree of acetylation (DA) on the gelation behaviors on addition of
      sodium carbonate for native and acetylated konjac glucomannan (KGM) samples with
      a DA range from 1.38 to 10.1 wt % synthesized using acetic anhydride in the
      presence of pyridine as catalyst was studied by dynamic viscoelastic
      measurements. At a fixed alkaline concentration (CNa), both the critical gelation
      times (tcr) and the plateau values of storage moduli (G'sat) of the KGM gels
      increased with increasing DA, while at a fixed ratio of alkaline concentrations
      to values of DA (CNa/DA), similar tcr and values independent of DA were observed.
      On the whole, increasing KGM concentration or temperature shortened the gelation
      time and enhanced the elastic modulus for KGM gel. The effect of deacetylation
      rate related to the CNa/DA on the gelation kinetics of the KGM samples was
      discussed.

PMID- 14715025
TI  - Galactose-substituted alginate 2: conformational aspects.
AB  - Galactose moieties have been introduced on the uronic groups of alginates from
      different sources via an N-glycosidic bond, thus affecting the net charge on the
      polymer chain. The modified polymers have been analyzed by means of viscosity and
      of high-performance size-exclusion chromatography combined with refractive index
      multiple angle laser light scattering (HPSEC-RI-MALLS) measurements. The latter
      technique enabled us to determine the molecular weight of the modified polymers,
      proving that the synthetic procedure did not affect the chemical integrity of the
      chain. The intrinsic viscosity and the radius of gyration data showed that the
      hydrodynamic properties of the polymer chain varied with the degree and the
      pattern of substitution. In the presence of a relatively low galactose content
      (up to 19%), a decrease of the hydrodynamic dimensions of the coil was
      experienced, while on increasing the degree of substitution (especially on GG
      diads) a re-extension of the chain was discovered. Measurements of intrinsic
      viscosity at different values of the degree of dissociation have demonstrated
      that this effect cannot be solely explained by the reduction of the charge
      density of the polymer. Rather, it implies the occurrence of conformational
      changes of the chain that are specific to the chemical nature of the site of
      substitution. These data have been supported by the values of the persistence
      length of the natural and modified polymers obtained with the Doty-Benoit
      equation. The chiro-optical properties of the modified polymers studied by means
      of circular dichroism (CD) spectroscopy confirmed that conformational variations
      occurred to the polymeric chain upon introduction of galactose residues.

PMID- 14715026
TI  - Preparation of ultrafine oxidized cellulose mats via electrospinning.
AB  - Ultrafine oxidized cellulose (OC) mats were prepared by oxidation of ultrafine
      cellulose mats produced by electrospinning and subsequent deacetylation of
      cellulose acetate for potential applications in nonwoven adhesion barriers. When
      ultrafine cellulose mats were oxidized with a mixture of HNO3/H3PO4 - NaNO2
      (2/1/1.4 v/v/wt %), their ultrafine mat structure remained unchanged. The yield
      and carboxyl content of OC mats were 86.7% and 16.8%, respectively. OC showed
      lower crystallinity than cellulose because the oxidation of cellulose proceeded
      via disruption of hydrogen bonds between cellulose chains. The swelling behaviors
      of ultrafine OC mats were dependent on the type of swelling solution. In a
      physiological salt solution, their degree of swelling was approximately 230%.

PMID- 14715027
TI  - Synthesis and physical characterization of poly(ethylene glycol)-gelatin
      conjugates.
AB  - Poly(ethylene glycol) (PEG) with the terminal group of active ester was coupled
      to the amino group of gelatin to prepare PEG-grafted gelatin (PEG-gelatin). The
      affinity chromatographic study revealed that the PEG-gelatin with high degrees of
      PEGylation did not adsorb onto the gelatin affinity column, in remarked contrast
      to gelatin alone and the PEG-gelatin with low PEGylation degrees. The former PEG
      gelatin showed a critical micelle concentration while it had the apparent
      molecular size of about 100 nm and a surface charge of almost zero. These
      findings indicate that the PEG-gelatin formed a micelle structure of which the
      surface is covered with PEG molecules grafted. When the body distribution of 125I
      labeled gelatin and PEG-gelatin after intravenous injection was evaluated, the
      radioactivity of micellar PEG-gelatin was retained in the blood circulation
      compared with that of gelatin and the PEG-gelatin of no micelle formation. At the
      same PEGylation degree, the blood concentration was significantly higher for the
      PEG-gelatin prepared from PEG with a molecular weight of 12 000 than that of
      molecular weights of 2000 and 5000. It is concluded that the PEG-gelatin is a
      drug carrier with a micelle structure which retains in the blood circulation.

PMID- 14715028
TI  - Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s with
      functional carbonate building blocks. 1. Chemical synthesis and their structural
      and physical characterization.
AB  - This study presents chemical synthesis, structural, and physical characterization
      of novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s
      P(BS-co-CC) bearing functional carbonate building blocks. First, five kinds of
      six-membered cyclic carbonate monomers, namely, trimethylene carbonate (TMC), 1
      methyl-1,3-trimethylene carbonate (MTMC), 2,2-dimethyl-1,3-trimethylene carbonate
      (DMTMC), 5-benzyloxytrimethylene carbonate (BTMC), and 5-ethyl-5-benzyloxymethyl
      trimethylene carbonate (EBTMC), were well prepared from ethyl chloroformate and
      corresponding diols at 0 degrees C in THF solution with our modified synthetic
      strategies. Then, a series of new P(BS-co-CC)s were synthesized at 210 degrees C
      through a simple combination of poly-condensation and ring-opening-polymerization
      (ROP) of hydroxyl capped PBS macromers and the prepared carbonate monomers, and
      titanium tetra-isopropoxide Ti(i-OPr)4 was used as a more suitable catalyst of 5
      candidate catalysts which could concurrently catalyze poly-condensation and ROP.
      By means of NMR, GPC, FTIR, and thermal analytical instruments, macromolecular
      structures and physical properties have been characterized for these aliphatic
      poly(ester carbonate)s. The experimental results indicated that novel
      biodegradable P(BS-co-CC)s were successfully synthesized with number average
      molecular weight Mn ranging from 24.3 to 99.6 KDa and various CC molar contents
      without any detectable decarboxylation and that the more bulky side group was
      attached to a cyclic carbonate monomer, the lower reactivity for its
      copolymerization would be observed. The occurrences of 13C NMR signal splitting
      of succinyl carbonyl attributed to the BS building blocks could be proposed due
      to the randomized sequences of BS and CC building blocks. FTIR characterization
      indicated two distinct absorption bands at 1716 and 1733 approximately 1735 cm(
      1), respectively, stemming from carbonyl stretching modes for corresponding BS
      and CC units. With regard to their thermal properties, it is seen that the
      synthesized P(BS-co-CC)s exhibited thermal degradation temperatures 10
      approximately 20 degrees C higher than that of PBS. On the basis of the
      synthesized P(BS-co-BTMC)s, new aliphatic poly(butylene succinate-co-5-hydroxy
      trimethylene carbonate)s were further synthesized, bearing hydrophilic hydroxyl
      pendant functional groups through an optimized Pd/C catalyzed hydrogenation.
      These semi-crystalline new biodegradable aliphatic copolymers with tunable
      physical properties and functional carbonate building blocks might be expected as
      potential new biomaterials.

PMID- 14715029
TI  - Small angle X-ray scattering of resistant starch type III.
AB  - Starch fraction, which is resistant to enzymatic digestion, is produced during
      retrogradation. This fraction, termed resistant starch type III (RSIII), has
      health benefits such as pre-biotic effects, improving lipid and cholesterol
      metabolism, and reducing the risk of colon cancer. The work presented in this
      paper is aimed at investigating the colloidal structure of native high amylose
      corn starch (HACS) and the RSIII polymorphs produced from it using small angle X
      ray scattering. Experimental scattering curves were fitted with appropriate
      theoretical models such as the "modified lamellar model". Our results show that
      retrogradation at low temperature leads to formation of polymorph B with
      crystallinity much lower than that of the granular form, but the lamellas are
      arranged in long-range periodicity. Conversely, retrogradation at high
      temperature leads to formation of polymorphs A and V with no defined periodicity.
      The degree of crystallinity is very low, and the system is better described as a
      dilute particulate system.

PMID- 14715030
TI  - Synthesis and characterization of glycopolymer-polypeptide triblock copolymers.
AB  - Glycopolymer-polypeptide triblock copolymers of the structure, poly(l-alanine)-b
      poly(2-acryloyloxyethyl-lactoside)-b-poly(l-alanine) (AGA), have been synthesized
      by sequential atom transfer radical polymerization (ATRP) and ring-opening
      polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyl
      oxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-d-galactopyranosyl)-(1-4)-2,3,6-tri-O
      acetyl-beta-d-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy
      complex system was used to generate a central glycopolymer block. Telechelic
      glycopolymers with diamino end groups were obtained by end group transformation
      and subsequently used as macroinitiators for ROP of l-alanine N-carboxyanhydride
      monomers (Ala-NCA). Gel permeation chromatography (GPC) and nuclear magnetic
      resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular
      weight and composition were controlled by both the molar ratios of the Ala-NCA
      monomer to macroinitiator and monomer conversion and exhibited a narrow
      distribution (Mw/Mn = 1.06-1.26). FT-IR spectroscopy of triblock copolymers
      revealed that the ratio of alpha-helix/beta-sheet increased with poly(l-alanine)
      block length. Of note, transmission electron microscopy (TEM) demonstrated that
      selected amphiphilic glycopolymer-polypeptide triblock copolymers self-assemble
      in aqueous solution to form nearly spherical aggregates of several hundreds
      nanometer in diameter. Significantly, the sequential application of ATRP and ROP
      techniques provides an effective method for producing triblock copolymers with a
      central glycopolymer block and flanking polypeptide blocks of defined
      architecture, controlled molecular weight, and low polydispersity.

PMID- 14715031
TI  - Osmotic observations on chemically cross-linked DNA gels in physiological salt
      solutions.
AB  - Neutralized DNA gels exhibit a reversible volume transition when CaCl2 is added
      to the surrounding aqueous NaCl solution. In this paper, a systematic study of
      the osmotic and mechanical properties of Na-DNA gels is presented to determine,
      qualitatively and quantitatively, the effect of Ca-Na exchange on the volume
      transition. It is found that in the absence of CaCl2 the DNA gels exhibit osmotic
      behavior similar to that of DNA solutions with reduced DNA concentration. At low
      CaCl2 concentration, the gel volume gradually decreases as the CaCl2
      concentration increases. Below the volume transition, the concentration
      dependence of the osmotic pressure can be satisfactorily described by a Flory
      Huggins-type equation. The Ca2+ ions primarily affect the third-order interaction
      term, which strongly increases upon the introduction of Ca2+ ions. The second
      order interaction term only slightly depends on the CaCl2 concentration. It is
      demonstrated that DNA gels cross-linked in solutions containing CaCl2 exhibit
      reduced osmotic mixing pressure. The concentration dependence of the shear
      modulus of DNA gels can be described by a single power law. The scaling exponent
      is practically independent of the NaCl concentration and increases with
      increasing CaCl2 content.

PMID- 14715032
TI  - Starch graft poly(methyl acrylate) loose-fill foam: preparation, properties and
      degradation.
AB  - Starch graft poly(methyl acrylate) (S-g-PMA) was prepared by ceric ion initiation
      of methyl acrylate in an aqueous corn starch slurry (prime starch) which
      maximized the accessibility of the starch for graft polymerization. A new ceric
      ion reaction sequence was established as starch-initiator-methyl acrylate
      followed by addition of a small amount of ceric ion solution when the graft
      polymerization was almost complete to quench the reaction. As a result of this
      improved procedure, no unreacted methyl acrylate monomer remained, and thus,
      essentially no ungrafted poly(methyl acrylate) homopolymer was formed in the
      final grafted product. Quantities of the high purity S-g-PMA so prepared in pilot
      scale were converted to resin pellets and loose-fill foam by single screw and
      twin screw extrusion. The use of prime starch significantly improved the physical
      properties of the final loose-fill foam, in comparison to foam produced from
      regular dry corn starch. The S-g-PMA loose-fill foam had compressive strength and
      resiliency comparable to expanded polystyrene but higher bulk density. The S-g
      PMA loose-fill foam also had better moisture and water resistance than other
      competitive starch-based materials. Studies indicated that the starch portion in
      S-g-PMA loose-fill foam biodegraded rapidly, whereas poly(methyl acrylate)
      remained relatively stable under natural environmental conditions.

PMID- 14715033
TI  - Synthesis and characterization of peptide-functionalized polymeric nanoparticles.

PMID- 14715034
TI  - Improving the activity of lipases from thermophilic organisms at mesophilic
      temperatures for biotechnology applications.

PMID- 14715035
TI  - How many steps/day are enough? Preliminary pedometer indices for public health.
AB  - Pedometers are simple and inexpensive body-worn motion sensors that are readily
      being used by researchers and practitioners to assess and motivate physical
      activity behaviours. Pedometer-determined physical activity indices are needed to
      guide their efforts. Therefore, the purpose of this article is to review the
      rationale and evidence for general pedometer-based indices for research and
      practice purposes. Specifically, we evaluate popular recommendations for
      steps/day and attempt to translate existing physical activity guidelines into
      steps/day equivalents. Also, we appraise the fragmented evidence currently
      available from associations derived from cross-sectional studies and a limited
      number of interventions that have documented improvements (primarily in body
      composition and/or blood pressure) with increased steps/day.A value of 10000
      steps/day is gaining popularity with the media and in practice and can be traced
      to Japanese walking clubs and a business slogan 30+ years ago. 10000 steps/day
      appears to be a reasonable estimate of daily activity for apparently healthy
      adults and studies are emerging documenting the health benefits of attaining
      similar levels. Preliminary evidence suggests that a goal of 10000 steps/day may
      not be sustainable for some groups, including older adults and those living with
      chronic diseases. Another concern about using 10000 steps/day as a universal step
      goal is that it is probably too low for children, an important target population
      in the war against obesity. Other approaches to pedometer-determined physical
      activity recommendations that are showing promise of health benefit and
      individual sustainability have been based on incremental improvements relative to
      baseline values. Based on currently available evidence, we propose the following
      preliminary indices be used to classify pedometer-determined physical activity in
      healthy adults: (i). <5000 steps/day may be used as a 'sedentary lifestyle
      index'; (ii). 5000-7499 steps/day is typical of daily activity excluding
      sports/exercise and might be considered 'low active'; (iii). 7500-9999 likely
      includes some volitional activities (and/or elevated occupational activity
      demands) and might be considered 'somewhat active'; and (iv). >or=10000 steps/day
      indicates the point that should be used to classify individuals as 'active'.
      Individuals who take >12500 steps/day are likely to be classified as 'highly
      active'.

PMID- 14715036
TI  - Heat illness in athletes: the dangerous combination of heat, humidity and
      exercise.
AB  - In 1980, 1700 people died during a prolonged heat wave in a region under-prepared
      for heat illness prevention. Dramatically underreported, heat-related pathology
      contributes to significant morbidity as well as occasional mortality in athletic,
      elderly, paediatric and disabled populations. Among US high school athletes, heat
      illness is the third leading cause of death. Significant risk factors for heat
      illness include dehydration, hot and humid climate, obesity, low physical
      fitness, lack of acclimatisation, previous history of heat stroke, sleep
      deprivation, medications (especially diuretics or antidepressants), sweat gland
      dysfunction, and upper respiratory or gastrointestinal illness. Many of these
      risk factors can be addressed with education and awareness of patients at risk.
      Dehydration, with fluid loss occasionally as high as 6-10% of bodyweight, appears
      to be one of the most common risk factors for heat illness in patients exercising
      in the heat. Core body temperature has been shown to rise an additional 0.15-0.2
      degrees C for every 1% of bodyweight lost to dehydration during exercise.
      Identifying athletes at risk, limiting environmental exposure, and monitoring
      closely for signs and symptoms are all important components of preventing heat
      illness. However, monitoring hydration status and early intervention may be the
      most important factors in preventing severe heat illness.

PMID- 14715037
TI  - Impact injuries in baseball : prevalence, aetiology and the role of equipment
      performance.
AB  - Baseball has one of the highest impact injury rates of all sports. These injuries
      are primarily attributed to impact by a ball after it has been hit, pitched or
      thrown. This paper will review the incidence and causal factors for impact
      injuries in baseball. Attention is given to the design and material properties of
      bats, in light of evidence suggesting balls hit into the infield from metal bats
      can reach velocities potentially lethal to defensive players. The distribution of
      bat mass along the long axis of the implement appears a major factor in the
      greater performance potential of metal bats over wooden bats of equal length and
      mass. The dynamic behaviour of baseballs has also been implicated in the severity
      of head and chest injuries experienced by players. Balls of greatly reduced
      stiffness have been introduced for junior play, but debate still remains over
      their performance and impact characteristics. The behaviour of the ball during
      high-speed impact with the bat has been the subject of relatively limited
      research, and the effect of manipulating baseball material properties to decrease
      batted-ball velocity is unclear. The value of batting helmets is evident in the
      observed reduction of head injuries in baseball, but the use of protective vests
      to decrease the incidence and severity of cardio-thoracic trauma appears to be
      contraindicated.

PMID- 14715040
TI  - Do we need drug therapy to manage mild hypertension in the elderly?
AB  - Mild hypertension (grade 1 or stage 1 hypertension) is defined as a systolic
      blood pressure of 140-159 mm Hg or a diastolic pressure of 90-99 mm Hg. According
      to current guidelines, patients with mild hypertension can be at low, medium,
      high or very high risk depending on the presence of other risk factors, target
      organ damage and associated cardiovascular or renal conditions. Guidelines
      recommend prompt initiation of antihypertensive treatment in patients at very
      high risk because of associated clinical conditions and this recommendation is
      strongly supported by the literature. Also patients at high risk must be treated
      without much delay, but it should be mentioned that the evidence is stronger for
      patients who are at high risk because of diabetes mellitus, than for patients at
      high risk because of left ventricular hypertrophy or the accumulation of >or = 3
      other risk factors. Patients at low and medium risk should be followed up and
      given advice on nonpharmacological measures and treatment should only be
      initiated in cases of persistently elevated blood pressure. However, this advice
      is based on indirect evidence and is currently not supported by randomised
      controlled trials. A survey on treatment of hypertension and implementation of
      World Health Organization/International Society of Hypertension (WHO/ISH)
      guidelines in primary care revealed that, respectively, only 20% and 33% of
      elderly men with mild hypertension at medium and high risk were treated with
      antihypertensive drugs and that this prevalence amounted to 67% in patients at
      very high risk; the prevalence was higher in patients with higher levels of blood
      pressure in each risk category.

PMID- 14715038
TI  - The role of exercise in the treatment of cardiovascular disease associated with
      type 2 diabetes mellitus.
AB  - The role of exercise training in the prevention and treatment of type 2 diabetes
      mellitus has been studied extensively over the past two decades. Although the
      primary treatment aim for patients with type 2 diabetes is metabolic control, the
      morbidity and mortality associated with the disease is more a function of
      cardiovascular disease. As exercise is associated with favourable reductions in
      the risk for cardiovascular disease in other high-risk populations, here we
      explore the role of exercise in the treatment of cardiovascular maladaptations
      associated with type 2 diabetes. The cardiovascular adaptation to type 2 diabetes
      is characterised by hypertrophy, stiffening and loss of functional reserve.
      Clinically, the cardiovascular adaptations to the diabetic state are associated
      with an increased risk for cardiovascular disease. Functionally, these
      adaptations have been shown to contribute to a reduced exercise capacity, which
      may explain the reduced cardiovascular fitness observed in this population.
      Exercise training is associated with improved exercise capacity in various
      populations, including type 2 diabetes. Several structural and functional
      adaptations within the cardiovascular system following exercise training could
      explain these findings, such as reductions in ventricular and vascular structural
      hypertrophy and compliance coupled with increased functional reserve. Although
      these cardiovascular adaptations to aerobic exercise training have been well
      documented in older populations with similar decrements in cardiovascular fitness
      and function, they have yet to be examined in patients with type 2 diabetes. For
      this reason, we contend that exercise training may be an excellent therapeutic
      adjunct in the treatment of diabetic cardiovascular disease.

PMID- 14715041
TI  - Effects of calcium supplementation on circulating lipids: potential
      pharmacoeconomic implications.
AB  - For about a century there has been recognition that calcium and lipids bind to
      one another in the gut, each interfering with the other's absorption. Calcium
      also causes malabsorption of bile acids, which is likely to contribute further to
      malabsorption of fat. High dietary calcium intakes may also have stimulatory
      effects on lipolysis. These mechanisms provide a basis for hypothesising that
      calcium supplementation may impact on circulating lipid concentrations, and there
      is now a significant amount of observational and trial data indicating that this
      is the case. The largest randomised controlled trial of calcium effects on lipids
      was carried out in 223 healthy postmenopausal women, and found that low density
      lipoprotein-cholesterol (LDL-C) decreased 6.3% and high density lipoprotein
      cholesterol (HDL-C) increased by 7.3% at 1-year. The resultant 16.4% increase in
      HDL-C/LDL-C ratio would be predicted to reduce cardiovascular event rates by 20
      30%, which is consistent with the available observational data. There are no
      trial data addressing this question and it is possible that other lipid-lowering
      agents, such as hydroxymethylglutaryl coenzyme A reductase inhibitors, might
      impact on cardiac event rates by mechanisms other than by lowering cholesterol
      levels. Therefore, caution is appropriate in incorporating these findings into
      clinical practice, but the balance of evidence suggests that calcium is a cost
      effective adjunct to the dietary management of hyperlipidaemia.

PMID- 14715039
TI  - Neuromuscular function after exercise-induced muscle damage: theoretical and
      applied implications.
AB  - Exercise-induced muscle damage is a well documented phenomenon particularly
      resulting from eccentric exercise. When eccentric exercise is unaccustomed or is
      performed with an increased intensity or duration, the symptoms associated with
      muscle damage are a common outcome and are particularly associated with
      participation in athletic activity. Muscle damage results in an immediate and
      prolonged reduction in muscle function, most notably a reduction in force
      generating capacity, which has been quantified in human studies through isometric
      and dynamic isokinetic testing modalities. Investigations of the torque-angular
      velocity relationship have failed to reveal a consistent pattern of change, with
      inconsistent reports of functional change being dependent on the muscle action
      and/or angular velocity of movement. The consequences of damage on dynamic, multi
      joint, sport-specific movements would appear more pertinent with regard to
      athletic performance, but this aspect of muscle function has been studied less
      often. Reductions in the ability to generate power output during single-joint
      movements as well as during cycling and vertical jump movements have been
      documented. In addition, muscle damage has been observed to increase the
      physiological demand of endurance exercise and to increase thermal strain during
      exercise in the heat. The aims of this review are to summarise the functional
      decrements associated with exercise-induced muscle damage, relate these
      decrements to theoretical views regarding underlying mechanisms (i.e. sarcomere
      disruption, impaired excitation-contraction coupling, preferential fibre type
      damage, and impaired muscle metabolism), and finally to discuss the potential
      impact of muscle damage on athletic performance.

PMID- 14715043
TI  - Efficacy and safety of donepezil in patients with Alzheimer's disease: results of
      a global, multinational, clinical experience study.
AB  - BACKGROUND: Donepezil has consistently been shown to be effective and well
      tolerated in the symptomatic treatment of Alzheimer's disease in placebo
      controlled clinical trials. It has been shown to provide significant benefits in
      cognition, global function and activities of daily living in patients with mild
      to-moderate Alzheimer's disease. However, in order to control for confounding
      factors, some clinical trials of donepezil have excluded patients with comorbid
      illness and concomitant medication use. OBJECTIVE: The objective of this study
      was to evaluate the efficacy, tolerability and safety of donepezil in a wider and
      more diverse sample of patients and centres than previous trials, reflecting
      routine clinical practice. METHODS: In this 12-week, open-label, multicentre
      trial, patients with probable mild-to-moderate Alzheimer's disease received
      donepezil 5 mg/day for 28 days, after which the dosage was increased to 10 mg/day
      according to the investigating clinician's judgement. Patients were enrolled at
      246 study centres in 18 countries worldwide. Cognition was assessed by a trained
      clinician using the Mini-Mental State Examination (MMSE) at baseline, week 4 and
      week 12 (or last visit). Changes in patient activity and social interaction were
      evaluated using a caregiver diary. Each week, caregivers recorded their
      impression of change compared with baseline on three aspects of patient behaviour
      using a 5-point scale. Efficacy analyses were performed on the intent-to-treat
      population. Significance was determined using the paired t-test (0.05
      significance level). Tolerability and safety were assessed by monitoring adverse
      events, physical examinations, vital signs, clinical laboratory test
      abnormalities and ECG findings throughout the study. RESULTS: A total of 1113
      patients received donepezil (mean baseline MMSE score [+/-SD] 18.74 +/- 5.21).
      989 (88.9%) patients completed the study; 59 (5%) patients discontinued because
      of adverse events. Most patients were taking at least one concomitant medication
      (n = 802; 72%) and had at least one comorbid medical condition (n = 745; 67%) on
      study entry. Donepezil significantly improved cognition compared with baseline at
      weeks 4 and 12, and at week 12 using a last observation carried forward (LOCF)
      analysis (all p < 0.0001). Mean change from baseline MMSE score (+/-SE) at week
      12-LOCF was +1.73 +/- 0.10. Donepezil was also associated with significant
      improvements in patient social interaction, engagement and interest, and
      initiation of pleasurable activities at all weekly assessments and week 12-LOCF
      (all p < 0.0001). Donepezil was generally well tolerated; adverse events were
      consistent with the known safety profile of donepezil. CONCLUSION: Donepezil
      treatment resulted in statistically significant improvements in cognition and
      patient activity and social behaviour, and was generally well tolerated despite
      high levels of comorbid illness and concomitant medication use. The results of
      this open-label study in a large patient population are consistent with those
      from controlled trials and support that donepezil is effective in the treatment
      of mild-to-moderate Alzheimer's disease in everyday practice.

PMID- 14715044
TI  - Ciprofloxacin extended release: in the treatment of urinary tract infections and
      uncomplicated pyelonephritis.
AB  - Ciprofloxacin extended release (XR) is a new oral formulation of a
      fluoroquinolone that allows once-daily administration while maintaining
      therapeutic serum levels of the drug. The maximum plasma concentrations (Cmax) of
      once-daily ciprofloxacin XR 500 mg was higher than that of twice-daily
      ciprofloxacin immediate release 250 mg and the Cmax of once-daily ciproflocaxin
      XR 1000 mg was higher than that of twice-daily ciprofloxacin 500 mg. No
      accumulation of ciprofloxacin XR at steady state was observed in healthy men and
      all other pharmacokinetic parameters were similar to those of the immediate
      release formulation. In patients with uncomplicated urinary tract infection
      (UTI), bacteriological eradication rates were similar in recipients of
      ciprofloxacin XR and immediate-release ciprofloxacin at the test-of-cure (TOC)
      visit, as were rates of persistence or new infection. Clinical cure rates were
      also similar in the two treatment groups. Bacteriological eradication occurred in
      89% of ciprofloxacin XR and 85% of immediate-release ciprofloxacin recipients
      with complicated UTIs or acute uncomplicated pyelonephritis at the TOC visit.
      Clinical cure rates were also similar in the two treatment groups. black triangle
      Ciprofloxacin XR was generally well tolerated in patients with uncomplicated or
      complicated UTIs or acute uncomplicated pyelonephritis and showed similar
      tolerability to that of the immediate-release formulation.

PMID- 14715042
TI  - Pharmacological treatments for persistent non-malignant pain in older persons.
AB  - Persistent non-malignant pain is common, often neglected and under-treated among
      older persons. Some older adults do not complain because they consider chronic
      pain to be a characteristic of normal aging. Physicians have concerns regarding
      adverse effects of pharmacological treatment. The model of the World Health
      Organization for treatment of cancer pain is generally accepted and also
      recommended for persistent non-cancer pain. Furthermore, non-pharmacological
      treatment should complement drug treatment whenever possible. An initial
      assessment and possible treatment of underlying causes of pain are pertinent.
      Modern pharmacological pain management is based on non-opioid and opioid
      analgesics. NSAIDs are among the most widely prescribed class of drugs in the
      world. The new cyclo-oxygenase-2 inhibitors such as celecoxib and rofecoxib offer
      an alternative for the treatment of mild-to-moderate pain in patients with a
      history of gastric ulcers or bleeding. Paracetamol (acetaminophen) is being used
      widely for the management of mild pain across all age groups as it has moderate
      adverse effects at therapeutic dosages. For moderate pain, a combination of non
      opioid analgesics and opioid analgesics with moderate pain relief properties
      (e.g. oxycodone, codeine, tramadol and tilidine/naloxone) is recommended. For
      severe pain, a combination of non-opioid analgesics and opioid analgesics with
      strong pain relief properties (e.g. morphine, codeine) is recommended. The least
      toxic means of achieving systemic pain relief should be used. For continuous
      pain, sustained-release analgesic preparations are recommended. Drugs should be
      given on a fixed time schedule, and possible adverse effects and interactions
      should be carefully monitored. Adjuvant drugs, such as antidepressants or
      anticonvulsants, can be very effective especially in the treatment of certain
      types of pain, such as in diabetic neuropathy. Effective pain management should
      result in decreased pain, increased function and improvement in mood and sleep.

PMID- 14715048
TI  - Treatment of the metabolic disturbances caused by antipsychotic drugs: focus on
      potential drug interactions.
AB  - The risk of excessive bodyweight gain, glucose dysregulation and hyperlipidaemia
      is differentially increased by conventional and atypical antipsychotic drugs.
      Switching or combining agents may be sufficient in some cases, but in many
      instances additional drug treatment will be required. This includes oral
      antidiabetics, insulin and agents to treat hyperlipidaemia, hypertension and
      platelet dysfunction, among others. Numerous pharmacokinetic and pharmacodynamic
      interactions with the antipsychotics are possible, although few have been tested
      in formal studies. After reviewing the literature, the authors provide
      preliminary guidelines to assist clinicians in drug selection for this complex
      and fragile clinical population.

PMID- 14715049
TI  - Pharmacokinetics of local anaesthetics in infants and children.
AB  - Amide local anaesthetics used for regional anaesthesia in paediatric patients are
      potent sodium channel blockers with marked stereospecificity, which consistently
      influences their action, especially their toxic action on the heart. At toxic
      concentrations, they induce severe arrhythmias with the potential for cardiac
      arrest. These agents are all bound to serum proteins, mainly to alpha(1)-acid
      glycoprotein (AAG), but also to human serum albumin. Protein binding ranges from
      65% (lidocaine) to more than 95% (bupivacaine, ropivacaine). Because AAG is a
      major acute phase protein, its concentration rapidly increases when inflammatory
      processes develop, particularly during the postoperative period. Neonates and
      infants have a lower AAG concentration in serum as compared with adults;
      therefore, their free fraction of local anaesthetics is increased accordingly.
      This has important clinical implications since, at least at steady state, the
      toxic effects of local anaesthetics are directly related to the free (unbound)
      drug concentration. After injection into the epidural space, absorption into the
      bloodstream follows a biphasic process. The buffering properties of the epidural
      space are important and prevent a rapid rise in concentration. In infants and
      children, the epidural space seems to protect patients in a similar manner.
      Moreover, it has been observed that the peak plasma concentration (C(max)) of
      ropivacaine is delayed in infants and children when compared with adults. The
      time to C(max) decreases from 90-120 minutes in infants aged less than 6 months
      to 30 minutes in children aged more than 8 years. This delay in C(max) may also
      be related to the lower clearance observed in younger patients. Local
      anaesthetics are metabolised by cytochrome P450 (CYP). The main CYP isoforms
      involved are CYP3A4 for lidocaine and bupivacaine and CYP1A2 for ropivacaine.
      CYP3A4 is not mature at birth but is partly replaced by CYP3A7. The intrinsic
      clearance of bupivacaine is only one-third of that in adults at 1 month of age,
      and two-thirds at 6 months. CYP1A2 is not fully mature before the age of 3 years.
      Indeed, the clearance of ropivacaine does not reach its maximum before the age of
      5 years. However, at birth this clearance is not as low as expected, and
      ropivacaine may be used even in younger patients.

PMID- 14715051
TI  - Recombinant human erythropoietin for the treatment of renal anaemia in children:
      no justification for bodyweight-adjusted dosage.
AB  - BACKGROUND: Drug doses for children are usually calculated by reducing adult
      doses in proportion to bodyweight. The clinically effective dose of recombinant
      human erythropoietin (epoetin) in children, however, seems to be higher than
      predicted by this calculation. OBJECTIVE: To determine the quantitative
      relationship between epoetin dose, bodyweight and response in children with end
      stage renal disease. PATIENTS AND METHODS: The time-course of haemoglobin in 52
      children during long-term treatment with epoetin beta was analysed by population
      pharmacodynamic modelling. Patients were 5-20 years old and weighed 16-53kg at
      the beginning of treatment. Epoetin beta was given intravenously three times per
      week after haemodialysis. Doses ranged from 110 to 7500IU (3-205 IU/kg).
      Haemoglobin versus time was described by assuming that the haemoglobin level
      rises after each dose due to the formation of new red blood cells, which then
      survive according to a logistic function. The initial rise after each dose was
      modelled in terms of absolute dose (not dose/kg). A parametric analysis was done
      with NONMEM, followed by a nonparametric analysis with NPAG. RESULTS: Dose
      response was best described by a sigmoid maximum-effect (E(max)) model with
      median E(max) = 0.29 g/dL, median 50% effective dose (ED(50)) = 2400IU and shape
      parameter gamma = 2. The estimated median survival time of the epoetin-induced
      red blood cells, tau, was 76 days. Neither of the dose-response parameters E(max)
      and ED(50) showed dependence on bodyweight. The median haemoglobin response to a
      standard dose, 0.042 g/dL for 1000IU, was similar to that reported for adults
      with intravenous administration. CONCLUSIONS: Doses for children in this age
      range should be specified as absolute amounts rather than amounts per unit
      bodyweight. Initial doses can be calculated individually, based on haemoglobin
      level before treatment, the desired haemoglobin at steady state and the median
      population parameters E(max), ED(50) and tau.

PMID- 14715053
TI  - Special section guest editorial. Ophthalmic diagnostics.

PMID- 14715054
TI  - Autofluorescence methods in ophthalmology.
AB  - An overview of the fluorophores of the eye, the methods used to measure ocular
      fluorescence, and the existing or ready-to-market instrumentation for the early
      diagnosis and monitoring of ophthalmic pathologies is presented. Emphasis is
      given to the impact that a more detailed knowledge of the fluorophores of the
      eye, their age and pathology relationship, and the considerable technology-driven
      progress in optical devices and components has had on the development of new
      compact yet powerful instruments for population screening and for patient follow
      ups, using fluorometry alone or in combination with other optical techniques such
      as light scattering.

PMID- 14715050
TI  - Pharmacokinetic factors in the adverse cardiovascular effects of antipsychotic
      drugs.
AB  - Antipsychotics may cause serious adverse cardiovascular effects, including
      prolonged QT interval and sudden death. This review considers antipsychotic
      induced cardiovascular events from three perspectives: high-risk drugs, high-risk
      individuals and high-risk drug interactions. Pharmacokinetic drug interactions
      involving the cytochrome P450 (CYP) enzymatic pathway and pharmacodynamic
      interactions leading to direct cardiotoxic effects are discussed. Original
      reports on antipsychotic-induced drug interactions are reviewed, with
      consideration of management guidelines. The literature was reviewed from 1
      January 1966 to 1 February 2002. The literature search revealed only 12 original
      articles published on antipsychotic drug interactions leading to cardiovascular
      adverse events. Only 4 of the 12 reports were prospective studies; the remainder
      were either retrospective or anecdotal.Although poor study designs preclude a
      definitive statement, it appears that pharmacokinetic interactions primarily
      involved the CYP2D6 and CYP3A4 enzymatic pathways. Those involving the CYP2D6
      isozyme included interactions with tricyclic antidepressants, selective
      serotonergic reuptake inhibitors and beta-blockers. Among these drug
      interactions, tricyclic antidepressants were most likely to reach clinical
      significance because of their limited therapeutic index. Drug interactions
      related to the CYP3A4 pathway were generally less severe, and involved high
      potency antipsychotics coadministered with inhibitors such as clarithromycin.
      Strategies are discussed for the management of adverse cardiovascular events
      related to antipsychotic drug interactions, including the use of an algorithm.
      Large, randomised, placebo-controlled studies with strict inclusion criteria are
      needed to determine the role that antipsychotics play in QT prolongation and
      sudden death.

PMID- 14715055
TI  - Ocular static and dynamic light scattering: a noninvasive diagnostic tool for eye
      research and clinical practice.
AB  - The noninvasive techniques of static and dynamic light scattering are emerging as
      valuable diagnostic tools for the early detection of ocular and systemic
      diseases. These include corneal abnormalities, pigmentary dispersion syndrome,
      glaucoma, cataract, diabetic vitreopathy, and possibly macular degeneration.
      Systemic conditions such as diabetes and possibly Alzheimer's disease can
      potentially be detected early via ocular tissues. The current state of
      development of these techniques for application to ophthalmic research and
      ultimately clinical practice is reviewed.

PMID- 14715056
TI  - Seeing the invisible: the challenge of imaging vitreous.
AB  - Imaging the vitreous is an attempt to view what is by design invisible. The
      inability to adequately image vitreous hinders a more complete understanding of
      its normal structure and function and how these change in aging and disease. The
      combined use of more than one technique could provide better imaging for
      investigational and clinical purposes. Past and present imaging methodologies are
      summarized and research and clinical techniques that are currently in development
      for future applications, are discussed. Dark-field slit microscopy has been used
      to characterize vitreous anatomy, both within the vitreous body as well as at the
      vitreo-retinal interface. In addition to this methodology, slit-lamp
      biomicroscopy; direct, indirect, and scanning laser ophthalmoscopies;
      ultrasonography; optical coherence tomography; magnetic resonance and Raman
      spectroscopies; and dynamic light-scattering methodologies for noninvasive
      evaluation are presented. Dark-field slit microscopy enables in vitro imaging
      without dehydration or tissue fixatives. Optical coherence tomography enables
      better in vivo visualization of the vitreo-retinal interface than scanning laser
      ophthalmoscopy and ultrasonography, but does not image the vitreous body. Dynamic
      light scattering can determine the average sizes of vitreous macromolecules
      within the vitreous body as well as possibly image the posterior vitreous cortex
      once detached, while Raman spectroscopy can detect altered vitreous molecules,
      such as glycated collagen and other proteins in diabetic vitreopathy.

PMID- 14715057
TI  - Ultrahigh-resolution optical coherence tomography.
AB  - In the past two decades, optical coherence tomography (OCT) has been established
      as an adjunct diagnostic technique for noninvasive, high-resolution, cross
      sectional imaging in a variety of medical fields. The rapid development of
      ultrabroad bandwidth light sources has recently enabled a significant improvement
      in OCT imaging resolution, demonstrating the potential of OCT to accomplish its
      original goal of performing noninvasive optical biopsies, i.e., the in vivo
      visualization of microstructural morphology in situ, which had previously only
      been possible with histopathology. In addition, these novel light sources might
      also enable the use of spectroscopic OCT, an extension of ultrahigh-resolution
      OCT, for enhancing image contrast as well as detecting spatially resolved
      functional, biochemical tissue information. State-of-the-art-light sources that
      now permit ultrahigh-resolution OCT covering the whole wavelength region from 500
      to 1600 nm are reviewed and fundamental limitations of OCT image resolution are
      discussed. Ex vivo ultrahigh-resolution OCT tomograms are compared with
      histological results; first clinical in vivo ultrahigh-resolution OCT and
      preliminary spectroscopic OCT results are presented and their impact for future
      clinical and research applications is discussed.

PMID- 14715058
TI  - Noninvasive detection of macular pigments in the human eye.
AB  - There is currently strong interest in developing noninvasive technologies for the
      detection of macular carotenoid pigments in the human eye. These pigments,
      consisting of lutein and zeaxanthin, are taken up from the diet and are thought
      to play an important role in the prevention of age-related macular degeneration,
      the leading cause of blindness in the elderly in the Western world. It may be
      possible to prevent or delay the onset of this debilitating disease with suitable
      dietary intervention strategies. We review the most commonly used detection
      techniques based on heterochromatic flicker photometry, fundus reflectometry, and
      autofluorescense techniques and put them in perspective with recently developed
      more molecule-specific Raman detection methods.

PMID- 14715059
TI  - Combined multiplanar optical coherence tomography and confocal scanning
      ophthalmoscopy.
AB  - We demonstrate the clinical application of a multiplanar imaging system that
      simultaneously acquires en face (C-scan) optical coherence tomography (OCT) and
      the corresponding confocal ophthalmoscopic images, along with cross-sectional (B
      scan) OCT at specifiable locations on the confocal image. The advantages of the
      simultaneous OCT and confocal acquisition as well as the challenges of
      interpreting the C-scan OCT images are discussed. Variations in tissue
      inclination with respect to the coherence wave surface alter the sampling of
      structures within the depth of the retina, producing novel slice orientations
      that are often challenging to interpret. We have evaluated for the first time the
      utility of C-scan OCT for a variety of pathologies, including melanocytoma,
      diabetic retinopathy, choroidal neovascular membrane, and macular pucker. Several
      remarkable new aspects of clinical anatomy were revealed using this new
      technique. The versatility of selective capture of C-scan OCT images and B-scan
      OCT images at precise points on the confocal image affords the clinician a more
      complete and interactive tool for 3-D imaging of retinal pathology.

PMID- 14715060
TI  - Measurement and imaging of birefringent properties of the human cornea with phase
      resolved, polarization-sensitive optical coherence tomography.
AB  - Optical coherence tomography (OCT) is an emerging technology for high-resolution,
      noncontact imaging of transparent and scattering media. Polarization-sensitive
      optical coherence tomography (PS-OCT) is a functional extension of OCT that can
      image birefringent properties of a biological sample. PS-OCT was used to measure
      and image retardation and birefringent axis orientation of in vitro human cornea.
      We used a two-channel PS-OCT system employing a phase-sensitive recording of the
      interferometric signals in two orthogonal polarization channels. Using an
      algorithm based on a Hilbert transform, it is possible to calculate the
      retardation and the slow axis orientation of the sample with only a single A-scan
      per transversal measurement location. While the retardation information is
      encoded in the amplitude ratio of the two interferometric signals, the axis
      orientation is encoded entirely in their phase difference. We present maps of
      retardation and the distribution of slow axis orientation of the human cornea in
      longitudinal cross-sections and en face images obtained at the back surface of
      the cornea. The retardation increases in a radial direction and with depth; the
      slow axis varies in the transversal direction. Knowledge of the retardation and
      the slow axis distribution of the cornea might improve nerve fiber polarimetry
      for glaucoma diagnostics and could be useful for diagnosing different types of
      pathologies of the cornea.

PMID- 14715061
TI  - New optical scheme for a polarimetric-based glucose sensor.
AB  - A new optical scheme to detect glucose concentration in the aqueous humor of the
      eye is presented. The ultimate aim is to apply this technique in designing a new
      instrument for, routinely and frequently, noninvasively monitoring blood glucose
      levels in diabetic patients without contact (no index matching) between the eye
      and the instrument. The optical scheme exploits the Brewster reflection of
      circularly polarized light off of the lens of the eye. Theoretically, this
      reflected linearly polarized light on its way to the detector is expected to
      rotate its state of polarization, owing to the presence of glucose molecules in
      the aqueous humor of a patient's eye. An experimental laboratory setup based on
      this scheme was designed and tested by measuring a range of known concentrations
      of glucose solutions dissolved in water. (c) 2004 Society of Photo-Optical
      Instrumentation Engineers.

PMID- 14715062
TI  - Digital image capture and quantification of subtle lens opacities in rodents.
AB  - A rapid, sensitive, and cost-effective method is reported for the subjective and
      objective documentation of subtle opacities in lenses of unanesthetized
      transgenic mice or selenite-injected rat pups as models for cataract formation.
      Animal eyes were dilated with eye drops and the animal was positioned in front of
      a Nikon FS2 photo slit lamp. Slit-lamp observations were recorded using a Canon
      Optura Pi digital video recorder. High-quality images of opacifying lenses were
      captured from the video and quantified using densitometry at progressive stages
      of opacification. In mice, targeted genomic deletion of the proteins CP49 (a lens
      specific filament) or Six5 (a model for myotonic dystrophy) resulted in subtle
      cataracts that were easily recorded and quantified using this instrumentation. In
      rats, the early progressive changes leading to a dense nuclear opacity caused by
      selenite injection were easily documented using this instrumentation. Low-cost
      components combined with a conventional slit-lamp ophthalmoscope were used to
      capture high-quality images of selected stages of cataract formation for
      quantitative analysis using commercial software.

PMID- 14715063
TI  - In vivo birefringence and thickness measurements of the human retinal nerve fiber
      layer using polarization-sensitive optical coherence tomography.
AB  - Glaucoma causes damage of the nerve fiber layer, which may cause loss of retinal
      birefringence. Therefore, PS-OCT is a potentially useful technique for the early
      detection of glaucoma. We built a fiber-based PS-OCT setup that produces real
      time images of the human retina in vivo, coregistered with retinal video images
      of the location of PS-OCT scans. Preliminary measurements of a healthy volunteer
      show that the double-pass phase retardation per unit of depth of the RNFL is not
      constant and varies with location, with values between 0.18 and 0.37 deg/microm.
      A trend in the preliminary measurements shows that the nerve fiber layer located
      inferior and superior to the optic nerve head is more birefringent than the
      thinner layer of nerve fiber tissue in the temporal and nasal regions.

PMID- 14715064
TI  - Toward a miniaturized fundus camera.
AB  - Retinopathy of prematurity (ROP) describes a pathological development of the
      retina in prematurely born children. In order to prevent severe permanent damage
      to the eye and enable timely treatment, the fundus of the eye in such children
      has to be examined according to established procedures. For these examinations,
      our miniaturized fundus camera is intended to allow the acquisition of wide-angle
      digital pictures of the fundus for on-line or off-line diagnosis and
      documentation. We designed two prototypes of a miniaturized fundus camera, one
      with graded refractive index (GRIN)-based optics, the other with conventional
      optics. Two different modes of illumination were compared: transscleral and
      transpupillary. In both systems, the size and weight of the camera were
      minimized. The prototypes were tested on young rabbits. The experiments led to
      the conclusion that the combination of conventional optics with transpupillary
      illumination yields the best results in terms of overall image quality.

PMID- 14715065
TI  - Theoretical modeling and evaluation of the axial resolution of the adaptive
      optics scanning laser ophthalmoscope.
AB  - We present axial resolution calculated using a mathematical model of the adaptive
      optics scanning laser ophthalmoscope (AOSLO). The peak intensity and the width of
      the axial intensity response are computed with the residual Zernike coefficients
      after the aberrations are corrected using adaptive optics for eight subjects and
      compared with the axial resolution of a diffraction-limited eye. The AOSLO
      currently uses a confocal pinhole that is 80 microm, or 3.48 times the width of
      the Airy disk radius of the collection optics, and projects to 7.41 microm on the
      retina. For this pinhole, the axial resolution of a diffraction-limited system is
      114 microm and the computed axial resolution varies between 120 and 146 microm
      for the human subjects included in this study. The results of this analysis
      indicate that to improve axial resolution, it is best to reduce the pinhole size.
      The resulting reduction in detected light may demand, however, a more
      sophisticated adaptive optics system. The study also shows that imaging systems
      with large pinholes are relatively insensitive to misalignment in the lateral
      positioning of the confocal pinhole. However, when small pinholes are used to
      maximize resolution, alignment becomes critical.

PMID- 14715066
TI  - Macular pigment Raman detector for clinical applications.
AB  - Clinical studies of carotenoid macular pigments (MP) have been limited by the
      lack of noninvasive, objective instruments. We introduce a novel noninvasive
      optical instrument, an MP Raman detector, for assessment of the carotenoid status
      of the human retina in vivo. The instrument uses resonant excitation of
      carotenoid molecules in the visible wavelength range, and quantitatively measures
      the highly specific Raman signals that originate from the single- and double-bond
      stretch vibrations of the pi-conjugated carotenoid molecule's carbon backbone.
      The instrument is a robust, compact device and suitable for routine measurements
      of MP concentrations in a clinical setting. We characterized and tested the
      instrument in clinical studies of human subjects to validate its function and to
      begin to establish its role as a possible screening test for macular pathologies.
      We also show that the MP Raman spectroscopy technology has potential as a novel,
      highly specific method for rapid screening of carotenoid antioxidant levels in
      large populations at risk for vision loss from age-related macular degeneration,
      the leading cause of blindness of the elderly in the developed world.

PMID- 14715067
TI  - Three-dimensional computer-automated threshold Amsler grid test.
AB  - We describe a novel method for testing a visual field that employs a computer
      monitor with displays of varying contrast that permits unprecedented resolution
      and characterization of the structure of scotomas in three dimensions. Patients
      are placed in front of a touch-sensitive computer screen at a fixed distance.
      With one eye covered, they focus on a central fixation marker and trace with
      their finger the areas on an Amsler grid that are missing from their field of
      vision. Increasing degrees of contrast of the Amsler grid are simulated by
      repeating the test at different gray-scale levels. The results are recorded and
      then displayed as topographical contour rings by the computer test program. The
      results can also be rendered as an immediate 3-D depiction of the central hill-of
      vision. Several clinical pilot studies have been conducted at the Doheny Eye
      Institute and more than 200 patients have been examined with this system so far.
      Conditions such as optic neuritis, anterior ischemic optic neuropathy (AION), age
      related macular degeneration (AMD), glaucoma, and ocular hypertension have been
      successfully assessed by this test. Each condition provides unique patterns that
      are most evident in 3-D. The 3-D computer-automated threshold Amsler grid test is
      an innovative and noninvasive visual field test. It provides several advantages
      over state-of-the-art standard automated perimetry, including: (1) additional
      information through 3-D depiction of scotomas, such as location, extent, slope,
      depth, and shape; (2) high angular resolution (1 deg compared with typically 6
      deg); (3) a simple test setup (merely a touch-sensitive computer monitor and the
      test software); (4) excellent patient compliance (spending 4 to 5 min per eye).
      In light of its promising initial tests, the 3-D visual field test appears to
      have the potential for the early detection and monitoring of various diseases
      over time.

PMID- 14715068
TI  - Calculation of ocular single-pass modulation transfer function and retinal image
      simulation from measurements of the polarized double-pass ocular point spread
      function.
AB  - The single-pass modulation transfer function (MTF(sgl)) is an important numerical
      parameter that can help elucidate the performance and some processes of the human
      visual system. In previous studies, the MTF(sgl) was calculated from double-pass
      point spread function (PSF) measurements. These measurements include a
      depolarized reflection component from the retina that introduces a measurement
      artifact, and they require long acquisition times to allow averaging to reduce
      speckle. To solve these problems, we developed a new ocular PSF analysis system
      (PSFAS) that uses polarization optics to eliminate the depolarized retinal
      reflection component, and a rotating prism to increase measurement speed.
      Validation experiments on one patient showed that the MTF(sgl) measured by PSFAS
      agrees closely with the MTF calculated from contrast sensitivity measurements. A
      simulated retinal image was calculated by convolution of Landolt rings with the
      calculated single-pass PSF provided by the PSFAS. The contrast characteristic
      then was calculated from the simulated retinal images. These results indicate
      that the MTF(sgl) obtained using the PSFAS may be a reliable measure of visual
      performance of the optics of the eye, including the optical effects of the
      retina. The simulated retinal images and contrast characteristics are useful for
      evaluating visual performance.

PMID- 14715069
TI  - Photographic patterns in macular images: representation by a mathematical model.
AB  - Normal macular photographic patterns are geometrically described and
      mathematically modeled. Forty normal color fundus photographs were digitized. The
      green channel gray-level data were filtered and contrast enhanced, then analyzed
      for concentricity, convexity, and radial resolution. The foveal data for five
      images were fit with elliptic quadratic polynomials in two zones: a central
      ellipse and a surrounding annulus. The ability of the model to reconstruct the
      entire foveal data from selected pixel values was tested. The gray-level patterns
      were nested sets of concentric ellipses. Gray levels increased radially, with
      retinal vessels changing the patterns to star shaped in the peripheral fovea. The
      elliptic polynomial model could fit a high-resolution green channel foveal image
      with mean absolute errors of 6.1% of the gray-level range. Foveal images were
      reconstructed from small numbers of selected pixel values with mean errors of
      7.2%. Digital analysis of normal fundus photographs shows finely resolved
      concentric elliptical foveal and star-shaped parafoveal patterns, which are
      consistent with anatomical structures. A two-zone elliptic quadratic polynomial
      model can approximate foveal data, and can also reconstruct it from small
      subsets, allowing improved macular image analysis.

PMID- 14715070
TI  - Noninvasive optoacoustic temperature determination at the fundus of the eye
      during laser irradiation.
AB  - In all fundus laser treatments of the eye, the temperature increase is not
      exactly known. In order to optimize treatments, an online temperature
      determination is preferable. We investigated a noninvasive optoacoustic method to
      monitor the fundus temperature during pulsed laser irradiation. When laser pulses
      are applied to the fundus, thermoelastic pressure waves are emitted, due to
      thermal expansion of the heated tissue. Using a constant pulse energy, the
      amplitude of the pressure wave increases linearly with an increase in the base
      temperature of between 30 and 80 degrees C. This method was evaluated in vitro on
      porcine retinal pigment epithelium (RPE) cell samples and clinically during
      selective RPE treatment with repetitive microsecond laser pulses. During the
      irradiation of porcine RPE with a neodymium-doped yttrium (Nd:YLF) laser (527 nm,
      1.7 micros, 500 Hz repetition rate, 160 mJ/cm(2)) an increase in the base
      temperature of 30+/-4 degrees C after 100 pulses was found. During patient
      treatments, a temperature increase of 60+/-11 degrees C after 100 pulses with a
      500-Hz repetition rate and 7+/-1 degrees C after 30 pulses with 100 Hz at 520
      mJ/cm(2) was found. All measured data were in good agreement with heat diffusion
      calculations. Optoacoustic methods can be used to noninvasively determine retinal
      temperatures during pulsed laser treatment of the eye. This technique can also be
      adapted to continuous-wave photocoagulation, photodynamic therapy and
      transpupillary thermotherapy, or other fields of laser-heated tissue.

PMID- 14715071
TI  - Classification of in vivo autofluorescence spectra using support vector machines.
AB  - An algorithm based on support vector machines (SVM), the most recent advance in
      pattern recognition, is presented for use in classifying light-induced
      autofluorescence collected from cancerous and normal tissues. The in vivo
      autofluorescence spectra used for development and evaluation of SVM diagnostic
      algorithms were measured from 85 nasopharyngeal carcinoma (NPC) lesions and 131
      normal tissue sites from 59 subjects during routine nasal endoscopy. Leave-one
      out cross-validation was used to evaluate the performance of the algorithms. An
      overall diagnostic accuracy of 96%, a sensitivity of 94%, and a specificity of
      97% for discriminating nasopharyngeal carcinomas from normal tissues were
      achieved using a linear SVM algorithm. A diagnostic accuracy of 98%, a
      sensitivity of 95%, and a specificity of 99% for detecting NPC were achieved with
      a nonlinear SVM algorithm. In a comparison with previously developed algorithms
      using the same dataset and the principal component analysis (PCA) technique, the
      SVM algorithms produced better diagnostic accuracy in all instances. In addition,
      we investigated a method combining PCA and SVM techniques for reducing the
      complexity of the SVM algorithms.

PMID- 14715072
TI  - Assessment of expressions of heat shock protein (HSP 72) and apoptosis after ArF
      excimer laser ablation of the cornea.
AB  - We immunohistochemically studied expressions of inducible heat shock protein 70
      (HSP 72) and apoptosis of corneas ablated with an ArF excimer laser. The
      temperature of corneal surfaces and laser-induced optical emission spectra were
      measured in real time as direct physical parameters related to the ablation
      mechanism. To the best of the authors' knowledge, there have been no experimental
      studies regarding the influence of physical parameters directly related to the
      ablation mechanism on corneal reactions at the cell level after laser ablation.
      The expression of HSP 72 was mainly localized in the regenerative epithelium,
      which was confirmed to be caused by laser ablation. The HSP 72 positive cell
      ratios had a correlation with thermal dose, which was derived from the measured
      time courses of temperature. Expressions of both HSP 72 and apoptosis depended on
      the thermal dose and elapsed time after ablation. HSP 72 and apoptosis could be
      seen up to a few hundred micrometers into the stroma, only at a fluence with an
      optical breakdown emission. This could have been caused by shock waves induced by
      the optical breakdown.

PMID- 14715073
TI  - Effect of target biological tissue and choice of light source on penetration
      depth and resolution in optical coherence tomography.
AB  - The effectiveness of an optical coherence tomography (OCT) system depends largely
      on the light source chosen. Published data on the optical properties of tissues
      are used to quantify the exponential attenuation of broadband light on transport
      through tissue. The effective attenuation coefficient is taken to be the sum of
      the absorption and scattering coefficients. This is used to demonstrate the
      effect on the spectra of a wide range of published OCT sources and the change in
      system resolution induced, and hence to comment on the suitability of different
      sources for OCT. The tissues studied include skin dermis, liver, and gallbladder.
      Sources at higher wavelengths are shown to be capable of high-resolution OCT
      imaging at greater depths. Titanium:sapphire lasers would be most suited for high
      resolution OCT over comparatively shallow depths into tissue. For lower
      resolution applications of OCT, a semiconductor optical amplifier and ytterbium
      fiber sources have better powers and bandwidths than superluminescent diodes. The
      resolution of OCT systems is not reduced significantly with imaging depth.

PMID- 14715074
TI  - Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents
      and studied with optical coherence tomography.
AB  - The depth of light penetration into highly scattering tissues can be improved by
      the application of biocompatible and osmotically active chemical agents. We
      compare the dynamics of optical clearing of tissue by the topical application of
      glycerol and dimethyl sulfoxide (DMSO) using optical coherence tomography (OCT).
      It is demonstrated experimentally that both agents can largely improve the OCT
      imaging depth for porcine stomach tissue. During a period of approximately 20 to
      30 min after the application of glycerol image contrast is also enhanced. This
      enhancement disappears over time. Such enhancement of image contrast is not
      observed with DMSO. Glycerol causes a higher degree of dehydration of the tissue
      than DMSO does. We suggest that these phenomena are caused by a two-stage
      diffusion of the chemicals. The first stage of diffusion is from the top tissue
      to the intercellular space, and the second is into the cell matrix. During the
      first stage, the imaging contrast could be improved by dehydration.

PMID- 14715076
TI  - Balanced detection for low-noise precision polarimetric measurements of optically
      active, multiply scattering tissue phantoms.
AB  - The use and advantages of balanced detection for making low-noise polarimetric
      measurements in turbid materials are demonstrated. The technique reduces the
      intensity noise originating from the laser and, in addition, makes possible a
      direct measurement of a component of the Stokes vector. When phase-locked
      detection is used with either amplitude or polarization modulation for
      polarimetric measurements in turbid media, one can obtain elements of the
      scattering matrix of very small magnitude. This methodology is used to measure
      optical activity and surviving linear polarization fractions in clear and turbid
      media containing glucose at physiologically relevant concentrations. The results
      are in agreement with Monte Carlo simulations of polarized light propagation in
      turbid media.

PMID- 14715075
TI  - Determination of burn depth by polarization-sensitive optical coherence
      tomography.
AB  - An assessment of burn depth is a key step in guiding the treatment of patients
      who have sustained thermal injuries. Polarization-sensitive optical coherence
      tomography (PS-OCT) might eventually provide the physician with a quantitative
      estimate of actual burn depth. Burns of various depths were induced by contacting
      rat skin with a brass rod preheated to 75 degrees C for 5, 15, or 30 s. Thermal
      injury denatured the collagen in the skin, and PS-OCT imaged the resulting
      reduction of birefringence through the depth-resolved changes in the polarization
      state of light propagated and reflected from the sample. Stokes vectors were
      calculated for each point in the PS-OCT images and the reduction in the rate of
      phase retardation between two orthogonal polarizations of light (deg/microm) was
      found to show a consistent trend with burn exposure time. PS-OCT is a noninvasive
      technique with potential to give the physician the information needed to
      formulate an optimal treatment plan for burn patients.

PMID- 14715077
TI  - Noninvasive determination of the optical properties of adult brain: near-infrared
      spectroscopy approach.
AB  - The basic parameters for physiological measurements provided by near-infrared
      spectroscopy are the local absorption and scattering coefficients. For the adult
      human head, they have been difficult to measure noninvasively because of the
      layered structure of the head. The results of measurements of absorption and
      reduced scattering coefficients through the forehead on 30 adult volunteers using
      a multidistance frequency domain method are reported. The optode separation
      distance ranged from 10 to 80 mm and measurements were recorded at 758 and 830
      nm. The measured absorption and reduced scattering coefficients of the forehead
      were used to evaluate the hemoglobin content in the scalp and brain as well as
      cerebral oxygen saturation. We found that cerebral oxygenation was relatively
      narrowly distributed within the subject group (the standard deviation was about
      3% for scalp and 6% for brain, respectively), whereas hemoglobin concentrations
      had a relatively broader distribution. We found that as the optode distance
      increased, the absorption coefficients increased and the scattering coefficients
      decreased, retrieving the optical values of scalp and brain for shorter and
      longer optode distances, respectively. We present the transition curves of the
      absorption and reduced scattering coefficients as functions of the optode
      distance. In order to verify the values for each layer, a comparison between the
      experimental data and a prediction based on the two-layer model of the adult head
      was carried out. The thicknesses of scalp and skull for the two-layer model were
      obtained by magnetic resonance imaging of a subject's head. The optical
      parameters obtained from the two-layer model agreed very well with those measured
      by the multidistance method.

PMID- 14715078
TI  - Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse
      optical spectroscopy: a case study.
AB  - Presurgical chemotherapy is widely used in the treatment of locally advanced
      breast cancer. Monitoring the response to therapy can improve survival and reduce
      morbidity. We employ a noninvasive, near-infrared method based on diffuse optical
      spectroscopy (DOS) to quantitatively monitor tumor response to neoadjuvant
      chemotherapy. DOS was used to monitor tumor response in one patient with locally
      advanced breast cancer throughout the course of her therapy. Measurements were
      performed prior to doxorubicin-cyclophosphamide therapy and at several time
      points over the course of three treatment cycles (68 days). Our results show
      strong tumor to normal (T/N) tissue contrast in total hemoglobin concentration
      (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation,
      S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10
      week period, the peak total hemoglobin and water dropped 56 and 67%,
      respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2)
      exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and
      water changes occurred within 5 days of treatment (26 and 37%, respectively).
      These data suggest that noninvasive, quantitative optical methods that
      characterize tumor physiology may be useful in assessing and optimizing
      individual response to neoadjuvant chemotherapy.

PMID- 14715079
TI  - Molecular and functional consequences of Smad4 C-terminal missense mutations in
      colorectal tumour cells.
AB  - Smad4 is an essential signal transducer of the transforming growth factor beta
      (TGF-beta) signalling pathway and has been identified as a tumour suppressor,
      being mutated in approx. 50% of pancreatic cancers and approx. 15% of colorectal
      cancers. Two missense mutations in the C-terminal domain of Smad4, D351H (Asp351-
      >His) and D537Y (Asp537-->Tyr), have been described recently in the human
      colorectal cancer cell lines CACO-2 and SW948 respectively [Woodford-Richens,
      Rowan, Gorman, Halford, Bicknell, Wasan, Roylance, Bodmer and Tomlinson (2001)
      Proc. Natl. Acad. Sci. U.S.A. 98, 9719-9723]. Previous work in vitro suggested
      that only Asp-351 was required for interaction with Smad2 [Wu, Fairman, Penry and
      Shi (2001) J. Biol. Chem. 276, 20688-20694]. In the present study, we investigate
      the functional consequences of these point mutations in vivo. We demonstrate that
      neither of these colorectal cancer cells undergo growth arrest in response to TGF
      beta, which can be explained, at least in part, by their inability to up-regulate
      cyclin-dependent kinase inhibitors p21 (CIP1 ) or p15 ( INK4b) after TGF-beta
      stimulation. Although the point-mutated Smad4s are expressed at normal levels in
      these colorectal cancer cells, they cannot interact with either TGF-beta-induced
      phosphorylated Smad2 or Smad3. As a result, these Smad4 mutants do not accumulate
      in the nucleus after TGF-beta stimulation, are not recruited to DNA by relevant
      Smad-binding transcription factors and cannot generate transcriptionally active
      DNA-bound complexes. Therefore both these colorectal tumour cells completely lack
      functional Smad4 activity owing to the missense mutations. Given the location of
      these mutations in the three-dimensional structure of the Smad4 C-terminal
      domain, the results also give us significant insights into Smad complex
      formation.

PMID- 14715080
TI  - Identification of a negative regulatory cis-element in the enhancer core region
      of the prostate-specific antigen promoter: implications for intersection of
      androgen receptor and nuclear factor-kappaB signalling in prostate cancer cells.
AB  - The NF-kappaB (nuclear factor-kappaB) transcription factors mediate activation of
      a large number of gene promoters containing diverse kappaB-site sequences. Here,
      PSA (prostate-specific antigen) was used as an AR (androgen receptor)-responsive
      gene to examine the underlying mechanism by which the NF-kappaB p65 transcription
      factor down-regulates the transcriptional activity of AR in cells. We observed
      that activation of NF-kappaB by TNFalpha (tumour necrosis factor alpha) inhibited
      both basal and androgen-stimulated PSA expression, and that this down-regulation
      occurred at the promoter level, as confirmed by the super-repressor IkappaBalpha
      (S32A/S36A), a dominant negative inhibitor of NF-kappaB. Using a linker-scanning
      mutagenesis approach, we identified a cis -element, designated XBE (X-factor
      binding element), in the AREc (androgen response element enhancer core) of the
      PSA promoter, which negatively regulated several AR-responsive promoters,
      including that of PSA. When three copies of XBE in tandem were juxtaposed to GRE4
      (glucocorticoid response element 4), a 4-6-fold reduction of inducible GRE4
      activity was detected in three different cell lines, LNCaP, ARCaP-AR and PC3-AR.
      Bioinformatics and molecular biochemical studies indicated that XBE is a kappaB
      like element that binds specifically to the NF-kappaB p65 subunit; consistent
      with these observations, only NF-kappaB p65, but not the NF-kappaB p50 subunit,
      was capable of inhibiting AR-mediated PSA promoter transactivation in LNCaP
      cells. In addition, our data also showed that AR binds to XBE, as well as to the
      kappaB consensus site, and that the transfection of AR inhibits the kappaB
      responsive promoter in transient co-transfection assays. Collectively, these data
      indicate that cross-modulation between AR and NF-kappaB p65 transcription factors
      may occur by a novel mechanism involving binding to a common cis -DNA element.

PMID- 14715082
TI  - Induction of p21 and p27 expression by amino acid deprivation of HepG2 human
      hepatoma cells involves mRNA stabilization.
AB  - mRNA abundance for a number of genes is increased by amino acid limitation. From
      an array screening study in HepG2 human hepatoma cells, it was established that
      one set of genes affected by amino acid availability is the set associated with
      cell-cycle control. The present study describes the increased expression of both
      mRNA and protein for the cyclin-dependent kinase inhibitors p21 and p27 in
      response to deprivation of HepG2 cells for a single essential amino acid,
      histidine. The increase in p21 and p27 mRNA content depended on de novo protein
      synthesis and involved a post-transcriptional mRNA stabilization component. For
      p21, increase in mRNA by histidine depletion appeared to be independent of p53
      transactivation, and the absolute level of p53 protein was unaffected by this
      treatment. Histidine limitation caused an increase in the phosphorylation of
      ERK1/ERK2 (extracellular-signal-regulated kinase), and inhibition of the ERK
      signal transduction pathway resulted in a reduction in the starvation-dependent
      increase in p21 mRNA. Blockade of the phosphoinositide 3-kinase and mTOR
      (mammalian target of rapamycin) pathways also blunted the increase in p21 mRNA
      content. These results document the amino acid-dependent control of the synthesis
      of specific cell-cycle regulators and help to explain the block at G1 phase after
      amino acid limitation.

PMID- 14715081
TI  - AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein
      coupled receptor signalling complexes.
AB  - Cell signalling mediated via GPCRs (G-protein-coupled receptors) is a major
      paradigm in biology, involving the assembly of receptors, G-proteins, effectors
      and downstream elements into complexes that approach in design 'solid-state'
      signalling devices. Scaffold molecules, such as the AKAPs (A-kinase anchoring
      proteins), were discovered more than a decade ago and represent dynamic
      platforms, enabling multivalent signalling. AKAP79 and AKAP250 were the first to
      be shown to bind to membrane-embedded GPCRs, orchestrating the interactions of
      various protein kinases (including tyrosine kinases), protein phosphatases (e.g.
      calcineurin) and cytoskeletal elements with at least one member of the
      superfamily of GPCRs, the prototypical beta2-adrenergic receptor. In this review,
      the multivalent interactions of AKAP250 with the cell membrane, receptor,
      cytoskeleton and constituent components are detailed, providing a working model
      for AKAP-based GPCR signalling complexes. Dynamic regulation of the AKAP-receptor
      complex is mediated by ordered protein phosphorylation.

PMID- 14715083
TI  - Quantitative analysis of nucleotide modulation of DNA binding by DnaC protein of
      Escherichia coli.
AB  - In this study, we have presented the first report of Escherichia coli DnaC
      protein binding to ssDNA (single stranded DNA) in an apparent hexameric form.
      DnaC protein transfers DnaB helicase onto a nascent chromosomal DNA replication
      fork at oriC, the origin of E. coli DNA replication. In eukaryotes, Cdc6 protein
      may play a similar role in the DNA helicase loading in the replication fork
      during replication initiation at the origin. We have analysed the DNA-binding
      properties of DnaC protein and a quantitative analysis of the nucleotide
      regulation of DnaC-DNA and DnaC-DnaB interactions using fluorescence anisotropy
      and affinity sensor analysis. DnaC protein bound to ssDNA with low to moderate
      affinity and the affinity was strictly modulated by nucleotides. DnaC bound ssDNA
      in the complete absence of nucleotides. The DNA-binding affinity was
      significantly increased in the presence of ATP, but not ATP[S]. In the presence
      of ADP, the binding affinity decreased approximately fifty-fold. Both anisotropy
      and biosensor analyses demonstrated that with DnaC protein, ATP facilitated ssDNA
      binding, whereas ADP facilitated its dissociation from ssDNA, which is a
      characteristic of an ATP/ADP switch. Both ssDNA and nucleotides modulate
      DnaB6*DnaC6 complex formation, which has significant implications in DnaC protein
      function. Based on the thermodynamic data provided in this study, we have
      proposed a mechanism of DnaB loading on to ssDNA by DnaC protein.

PMID- 14715084
TI  - Novel non-viral method for transfection of primary leukemia cells and cell lines.
AB  - BACKGROUND: Tumor cells such as leukemia and lymphoma cells are possible targets
      for gene therapy. However, previously leukemia and lymphoma cells have been
      demonstrated to be resistant to most of non-viral gene transfer methods. METHODS:
      The aim of this study was to analyze various methods for transfection of primary
      leukemia cells and leukemia cell lines and to improve the efficiency of gene
      delivery. Here, we evaluated a novel electroporation based technique called
      nucleofection. This novel technique uses a combination of special electrical
      parameters and specific solutions to deliver the DNA directly to the cell nucleus
      under mild conditions. RESULTS: Using this technique for gene transfer up to 75%
      of primary cells derived from three acute myeloid leukemia (AML) patients and
      K562 cells were transfected with the green flourescent protein (GFP) reporter
      gene with low cytotoxicity. In addition, 49(+/- 9.7%) of HL60 leukemia cells
      showed expression of GFP. CONCLUSION: The non-viral transfection method described
      here may have an impact on the use of primary leukemia cells and leukemia cell
      lines in cancer gene therapy.

PMID- 14715086
TI  - Subcuticular microstructure of the hornet's gaster: Its possible function in
      thermoregulation.
AB  - The present study set out to elucidate the structure and function of the large
      subcuticular air sacs encountered in the gaster of the Oriental hornet Vespa
      orientalis (Hymenoptera, Vespinae). Gastral segments I, II, III, together with
      the anterior portion of segment IV, comprise the greater volume of the gaster,
      and inside them, beneath the cuticle, are contained not only structures that
      extend throughout their entire length, like the alimentary canal, and the nerve
      cord with its paired abdominal ganglia, situated near the cuticle in the ventral
      side, but also the heart, which is actually a muscular and dorsally located blood
      vessel that pumps blood anteriorly, toward the head of the hornet. The mentioned
      structures take up only a small volume of the gaster, while the rest is occupied
      by air sacs and tracheal ducts that also extend longitudinally. Interposed
      between the two air sacs, there is a hard partition and above it, at the center -
      a paired tracheal duct that extends the entire length of the air sacs. The
      endothelium of the air sacs is very anfractuous, thereby enlarging and
      strengthening the surface area. In each gastral segment there is an aperture for
      the entry of air, namely, a spiracle. Additionally, in each segment, in the
      antero-lateral aspect of its tergum and situated between two successive segments,
      there is an intersegmental conjunctive bearing parallel slits of 1-2 microM in
      width and 10-30 microM in length. The latter are arranged concentrically around
      bundles of tracheae that traverse the cuticle from segment to segment. From the
      upper rims of the slits are suspended downward fringe-like structures or
      "shutters" ranging between 3-10 microM in length. We discuss the possibility that
      the Oriental hornet resorts to internal circulation of air, along with a
      thermoelectric heat pump mechanism, in order to achieve cooling and
      thermoregulation of its body.

PMID- 14715085
TI  - Impact of cancer occurrence on health-related quality of life: a longitudinal pre
      post assessment.
AB  - BACKGROUND: Investigations focusing and implementing on the impact of cancer on
      health-related quality of life (HRQoL) by the way of a mean comparison between
      cancer patients and subjects from the general population, are scarce and usually
      cross-sectional. Longitudinal application of HRQoL instruments to a general,
      initially healthy population allows for change to be assessed as an event occurs,
      rather than afterwards. The objective of the present study was to investigate the
      impact of new cancer on HRQoL. METHODS: The 36-item Short Form (SF-36) and 12
      item General Health Questionnaire (GHQ-12) were applied to the French SU.VI.MAX
      cohort in 1996 and 1998. A controlled longitudinal study was used to determine
      the impact on HRQoL of newly diagnosed cancer: 84 patients with cancer that
      occurred between the 2 HRQoL measures were compared with 420 age- and sex-matched
      cancer-free controls. RESULTS: Initial HRQoL level was similar in the two groups.
      A new cancer had a particularly marked effect on the SF-36 Physical functioning,
      Role-physical and General health dimensions (more than 6.6-point difference in
      change in HRQoL evolution on a 0-100 scale). The Bodily pain and Vitality
      dimensions were less severely affected (difference in change varying from 4.4 to
      6.3 points), and there was no effect on either the GHQ-12 score or the SF-36
      Mental health, Role-emotional and Social functioning dimensions. CONCLUSIONS: The
      negative impact of cancer on the lives of patients was assessed in terms of
      HRQoL. The aspects most likely to be affected were those with a physical
      component, and general health perceptions. These results can thus help quantify
      the impact of a new cancer on HRQoL evolution and potentially facilitate early
      intervention by identifying the most affected HRQoL domains.

PMID- 14715087
TI  - Consensus structural models for the amino terminal domain of the retrovirus
      restriction gene Fv1 and the murine leukaemia virus capsid proteins.
AB  - BACKGROUND: The mouse Fv1 (friend virus) susceptibility gene inhibits the
      development of the murine leukaemia virus (MLV) by interacting with its capsid
      (CA) protein. As no structures are available for these proteins we have
      constructed molecular models based on distant sequence similarity to other
      retroviral capsid proteins. RESULTS: Molecular models were constructed for the
      amino terminal domains of the probable capsid-like structure for the mouse Fv1
      gene product and the capsid protein of the MLV. The models were based on sequence
      alignments with a variety of other retrovirus capsid proteins. As the sequence
      similarity of these proteins with MLV and especially Fv1 is very distant, a
      threading method was employed that incorporates predicted secondary structure and
      multiple sequence information. The resulting models were compared with equivalent
      models constructed using the sequences of the capsid proteins of known structure.
      CONCLUSIONS: These comparisons suggested that the MLV model should be accurate in
      the core but with significant uncertainty in the loop regions. The Fv1 model may
      have some additional errors in the core packing of its helices but the resulting
      model gave some support to the hypothesis that it adopts a capsid-like structure.

PMID- 14715088
TI  - Genetic diversity and relationships in mulberry (genus Morus) as revealed by RAPD
      and ISSR marker assays.
AB  - BACKGROUND: The genus Morus, known as mulberry, is a dioecious and cross
      pollinating plant that is the sole food for the domesticated silkworm, Bombyx
      mori. Traditional methods using morphological traits for classification are
      largely unsuccessful in establishing the diversity and relationships among
      different mulberry species because of environmental influence on traits of
      interest. As a more robust alternative, PCR based marker assays including RAPD
      and ISSR were employed to study the genetic diversity and interrelationships
      among twelve domesticated and three wild mulberry species. RESULTS: RAPD analysis
      using 19 random primers generated 128 discrete markers ranging from 500-3000 bp
      in size. One-hundred-nineteen of these were polymorphic (92%), with an average of
      6.26 markers per primer. Among these were a few putative species-specific
      amplification products which could be useful for germplasm classification and
      introgression studies. The ISSR analysis employed six anchored primers, 4 of
      which generated 93 polymorphic markers with an average of 23.25 markers per
      primer. Cluster analysis of RAPD and ISSR data using the WINBOOT package to
      calculate the Dice coefficient resulted into two clusters, one comprising
      polyploid wild species and the other with domesticated (mostly diploid) species.
      CONCLUSION: These results suggest that RAPD and ISSR markers are useful for
      mulberry genetic diversity analysis and germplasm characterization, and that
      putative species-specific markers may be obtained which can be converted to SCARs
      after further studies.

PMID- 14715090
TI  - VKCDB: voltage-gated potassium channel database.
AB  - BACKGROUND: The family of voltage-gated potassium channels comprises a
      functionally diverse group of membrane proteins. They help maintain and regulate
      the potassium ion-based component of the membrane potential and are thus central
      to many critical physiological processes. VKCDB (Voltage-gated potassium [K]
      Channel DataBase) is a database of structural and functional data on these
      channels. It is designed as a resource for research on the molecular basis of
      voltage-gated potassium channel function. DESCRIPTION: Voltage-gated potassium
      channel sequences were identified by using BLASTP to search GENBANK and
      SWISSPROT. Annotations for all voltage-gated potassium channels were selectively
      parsed and integrated into VKCDB. Electrophysiological and pharmacological data
      for the channels were collected from published journal articles. Transmembrane
      domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple
      sequence alignments of conserved domains of channels of the four Kv families and
      the KCNQ family are also included. Currently VKCDB contains 346 channel entries.
      It can be browsed and searched using a set of functionally relevant categories.
      Protein sequences can also be searched using a local BLAST engine. CONCLUSIONS:
      VKCDB is a resource for comparative studies of voltage-gated potassium channels.
      The methods used to construct VKCDB are general; they can be used to create
      specialized databases for other protein families. VKCDB is accessible at
      http://vkcdb.biology.ualberta.ca.

PMID- 14715089
TI  - Identification of polymorphic tandem repeats by direct comparison of genome
      sequence from different bacterial strains: a web-based resource.
AB  - BACKGROUND: Polymorphic tandem repeat typing is a new generic technology which
      has been proved to be very efficient for bacterial pathogens such as B.
      anthracis, M. tuberculosis, P. aeruginosa, L. pneumophila, Y. pestis. The
      previously developed tandem repeats database takes advantage of the release of
      genome sequence data for a growing number of bacteria to facilitate the
      identification of tandem repeats. The development of an assay then requires the
      evaluation of tandem repeat polymorphism on well-selected sets of isolates. In
      the case of major human pathogens, such as S. aureus, more than one strain is
      being sequenced, so that tandem repeats most likely to be polymorphic can now be
      selected in silico based on genome sequence comparison. RESULTS: In addition to
      the previously described general Tandem Repeats Database, we have developed a
      tool to automatically identify tandem repeats of a different length in the genome
      sequence of two (or more) closely related bacterial strains. Genome comparisons
      are pre-computed. The results of the comparisons are parsed in a database, which
      can be conveniently queried over the internet according to criteria of practical
      value, including repeat unit length, predicted size difference, etc. Comparisons
      are available for 16 bacterial species, and the orthopox viruses, including the
      variola virus and three of its close neighbors. CONCLUSIONS: We are presenting an
      internet-based resource to help develop and perform tandem repeats based
      bacterial strain typing. The tools accessible at http://minisatellites.u-psud.fr
      now comprise four parts. The Tandem Repeats Database enables the identification
      of tandem repeats across entire genomes. The Strain Comparison Page identifies
      tandem repeats differing between different genome sequences from the same
      species. The "Blast in the Tandem Repeats Database" facilitates the search for a
      known tandem repeat and the prediction of amplification product sizes. The
      "Bacterial Genotyping Page" is a service for strain identification at the
      subspecies level.

PMID- 14715091
TI  - Using 3D Hidden Markov Models that explicitly represent spatial coordinates to
      model and compare protein structures.
AB  - BACKGROUND: Hidden Markov Models (HMMs) have proven very useful in computational
      biology for such applications as sequence pattern matching, gene-finding, and
      structure prediction. Thus far, however, they have been confined to representing
      1D sequence (or the aspects of structure that could be represented by character
      strings). RESULTS: We develop an HMM formalism that explicitly uses 3D
      coordinates in its match states. The match states are modeled by 3D Gaussian
      distributions centered on the mean coordinate position of each alpha carbon in a
      large structural alignment. The transition probabilities depend on the spread of
      the neighboring match states and on the number of gaps found in the structural
      alignment. We also develop methods for aligning query structures against 3D HMMs
      and scoring the result probabilistically. For 1D HMMs these tasks are
      accomplished by the Viterbi and forward algorithms. However, these will not work
      in unmodified form for the 3D problem, due to non-local quality of structural
      alignment, so we develop extensions of these algorithms for the 3D case. Several
      applications of 3D HMMs for protein structure classification are reported. A good
      separation of scores for different fold families suggests that the described
      construct is quite useful for protein structure analysis. CONCLUSION: We have
      created a rigorous 3D HMM representation for protein structures and implemented a
      complete set of routines for building 3D HMMs in C and Perl. The code is freely
      available from http://www.molmovdb.org/geometry/3dHMM, and at this site we also
      have a simple prototype server to demonstrate the features of the described
      approach.

PMID- 14715093
TI  - Radioantibodies: where do they fit in?

PMID- 14715092
TI  - Physicochemical characterization of the endotoxins from Coxiella burnetii strain
      Priscilla in relation to their bioactivities.
AB  - BACKGROUND: Coxiella burnetii is the etiological agent of Q fever found
      worldwide. The microorganism has like other Gram-negative bacteria a
      lipopolysaccharide (LPS, endotoxin) in its outer membrane, which is important for
      the pathogenicity of the bacteria. In order to understand the biological activity
      of LPS, a detailed physico-chemical analysis of LPS is of utmost importance.
      RESULTS: The lipid A moiety of LPS is tetraacylated and has longer (C-16) acyl
      chains than most other lipid A from enterobacterial strains. The two ester-linked
      3-OH fatty acids found in the latter are lacking. The acyl chains of the C.
      burnetii endotoxins exhibit a broad melting range between 5 and 25 degrees C for
      LPS and 10 and 40 degrees C for lipid A. The lipid A moiety has a cubic inverted
      aggregate structure, and the inclination angle of the D-glucosamine disaccharide
      backbone plane of the lipid A part with respect to the membrane normal is around
      40 degrees. Furthermore, the endotoxins readily intercalate into phospholipid
      liposomes mediated by the lipopolysaccharide-binding protein (LBP). The endotoxin
      induced tumor necrosis factor alpha (TNFalpha) production in human mononuclear
      cells is one order of magnitude lower than that found for endotoxins from
      enterobacterial strains, whereas the same activity as in the latter compounds is
      found in the clotting reaction of the Limulus amebocyte lysate assay.
      CONCLUSIONS: Despite a considerably different chemical primary structure of the
      C. burnetii lipid A in comparison with enterobacterial lipid A, the data can be
      well understood by applying the previously presented conformational concept of
      endotoxicity, a conical shape of the lipid A moiety of LPS and a sufficiently
      high inclination of the sugar backbone plane with respect to the membrane plane.
      Importantly, the role of the acyl chain fluidity in modulating endotoxicity now
      becomes more evident.

PMID- 14715094
TI  - 45th annual meeting of the American Society of Hematology. December 6-9, 2003,
      San Diego, California.

PMID- 14715097
TI  - Primary adrenal lymphoma.
AB  - Primary adrenal lymphoma is a rare extranodal lymphoma with characteristic
      clinical features including a high incidence of bilateral involvement,
      predominantly diffuse large B-cell histology, and a low incidence of extra
      adrenal disease at diagnosis. Patients are most commonly older men presenting
      with fever, lumbar pain, and/or symptoms of adrenal insufficiency. Prolonged
      disease-free survival appears uncommon, which may reflect a publication bias
      and/or the presence of additional adverse prognostic factors at diagnosis in most
      patients. Given the rarity of this disease, no prospective chemotherapy studies
      have been reported. Unresolved therapeutic issues include the optimal
      chemotherapy regimen (with vs. without monoclonal antibody), the role of
      bilateral adrenalectomy and/or adjuvant radiation therapy, and the need for
      central nervous system prophylaxis, given recent reports raising the possibility
      of a high risk of parenchymal or meningeal relapse. Multicenter collaborative
      retrospective reviews and prospective trials are needed to address these issues.

PMID- 14715098
TI  - An update of the epidemiology of non-Hodgkin's lymphoma.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) has increased approximately 80%
      since the 1970s, and is now the fifth most common cancer in the United States.
      The incidence of NHL is approximately 50% higher among men than women and 35%
      higher among white people than black people. The incidence rates of all subtypes
      of NHL have increased, especially diffuse large-cell and immunoblastic subtypes.
      Extranodal NHL has increased more rapidly than nodal NHL. The overall NHL
      incidence rates stabilized in the early 1990s and then began to decrease between
      1996 and 2000, resulting in part from a decrease in the incidence of AIDS. The
      incidence of NHL types not associated with AIDS and NHL in groups at low risk of
      AIDS has continued to increase throughout the 1990s. The increasing incidence of
      NHL is poorly understood. Improved diagnostic techniques, the effects of the
      human immunodeficiency virus epidemic, and immunosuppressive therapies accounted
      for only one third of the increase. Increase in NHL may be attributed to
      immunodeficiency, various infections, familial aggregation, blood transfusion,
      genetic susceptibility to NHL, diet, and chemical exposures to pesticides and
      solvents. Some studies also suggest that associations between risk factors and
      specific NHL subtypes may be stronger than associations between the same risk
      factors and NHL in aggregate. Future epidemiologic studies should incorporate the
      new World Health Organization classification of NHL and new techniques such as
      cytogenetic molecular analyses to identify subtype-specific etiologic factors.
      Evaluation of polymorphisms in genes involved in immune function, inflammation,
      and the activation or detoxification of environmental and occupational chemicals
      is also warranted.

PMID- 14715099
TI  - Results of a phase II multicenter trial of pentostatin and rituximab in patients
      with low grade B-cell non-Hodgkin's lymphoma: an effective and minimally toxic
      regimen.
AB  - This study explored the efficacy and toxicity of the combination of pentostatin
      and rituximab, effective single agents in low-grade non-Hodgkin's lymphoma (NHL).
      Sixty patients with previously treated low-grade NHL were enrolled. Except for
      day 1, both drugs were administered weekly for 4 weeks, with week 5 off. During
      week 1 (day 1) only rituximab was given; subsequent weekly treatments included
      both drugs. Patients received a minimum of 2 five-week cycles in order to be
      evaluable for efficacy. Responses were evaluated on week 5 of cycle 2. If partial
      response (PR) or stable disease (SD) responses were noted, 2 additional cycles
      were administered. Final evaluations were done on week 5 of cycle 4. Of 60
      patients, 58.3% had an Eastern Cooperative Oncology Group performance status (PS)
      of 0, and 41.7% had PS of 1; 31.7% and 51.7% had stage III or stage IV disease,
      respectively. Histology included follicular center, follicular, grade I (45%), II
      (21.7%), III (1.7%), and small lymphocytic (31.7%). Seventeen patients had prior
      chemotherapy, but no patients had received prior pentostatin or rituximab. Median
      age was 60.3 years (range, 32.5-84.7 years). Among 57 evaluable patients, 77%
      responded (22.3% complete response [CR], 3.5% unconfirmed CR, 35.1% PR, and 10.5%
      unconfirmed PR); 19.3% had SD, and 8.8% progressive disease (PD). Response rate
      among previously untreated patients was 83% versus 63% in previously treated
      patients. Median duration of response was 11 months (range, 2.3-22.2 months);
      median time to progression was 15 months (range, < 1-25 months). Neutropenia was
      the only adverse event experienced by >/= 10% of patients. Six deaths were caused
      by PD, and one death each was caused by acute respiratory distress, possibly
      related respiratory failure, and cardiac toxicity. These results suggest the
      combination of pentostatin/rituximab is well tolerated and active in low-grade
      lymphoma.

PMID- 14715100
TI  - Denileukin diftitox and hyper-CVAD in the treatment of human T-cell lymphotropic
      virus 1-associated acute T-cell leukemia/lymphoma.
AB  - We report a case of human T-cell lymphotropic virus 1 (HTLV-1)-associated adult T
      cell leukemia/lymphoma (ATL) in clinical remission > 1 year after therapy with
      denileukin diftitox and hyper-CVAD (hyperfractionated
      cyclophosphamide/doxorubicin/vincristine/decadron). The patient presented with
      leukocytosis, anemia, and thrombocytopenia, and bone marrow biopsy demonstrated
      extensive myelofibrosis and infiltration with leukemic T cells. Initial therapy
      with 4 cycles of denileukin diftitox resulted in restoration of normal
      hematopoiesis and a reduction in bone marrow myelofibrosis. After disease
      progression, 4 cycles of hyper-CVAD were administered and a complete clinical
      remission was achieved. The patient remains free of disease with normal
      hematopoiesis and has continued maintenance therapy with denileukin diftitox for
      1 year. This case demonstrates clinical improvement of myelofibrosis and acute T
      cell leukemia after denileukin diftitox administration, suggesting that
      denileukin diftitox may affect the paracrine secretion of HTLV-1-associated
      clinical manifestations of ATL.

PMID- 14715101
TI  - Mood alterations in patients treated with chlorambucil.
AB  - The alkylating agent chlorambucil produces dose-limiting myelosuppression but can
      also cause rare central nervous system toxicities, including seizures, when given
      in high doses. Patients with lymphoma who were receiving intermittent pulsed oral
      doses of 10-12 mg/m2 chlorambucil per day for 5 days experienced marked mood
      alterations during therapy. These effects, which have not been reported
      previously, involved sleep alterations, anxiety and restlessness, irritability,
      and depression. All effects remitted immediately after the final day of the
      dosing regimen. Mood alterations should be added to the known list of
      chlorambucil-related toxicities and can occur with commonly used oral dosing
      schedules.

PMID- 14715102
TI  - A phase II study of heat shock protein-peptide complex-96 vaccine therapy in
      patients with indolent non-Hodgkin's lymphoma.

PMID- 14715103
TI  - POEMS syndrome.

PMID- 14715104
TI  - The HERstory of breast cancer revealed.

PMID- 14715105
TI  - Benefit of letrozole in postmenopausal women after five years of tamoxifen
      therapy for early-stage breast cancer.

PMID- 14715106
TI  - Pegylated liposomal doxorubicin in the treatment of breast cancer.
AB  - Anthracyclines, particularly conventional doxorubicin, play an important role in
      the treatment of breast cancer, both in the adjuvant and metastatic settings.
      However, the benefits of conventional doxorubicin in terms of antitumor activity
      are limited by its therapeutic index. Liposomal formulations were developed to
      increase the therapeutic index of conventional doxorubicin. Pegylated liposomal
      doxorubicin, the most widely studied liposomal doxorubicin formulation in breast
      cancer, has been evaluated in > 20 clinical trials. Pegylated liposomal
      doxorubicin provides tumor-targeted efficacy without many of the toxicities
      associated with conventional doxorubicin, including myelosuppression, alopecia,
      nausea and vomiting, and most importantly, cardiac toxicity. As a single agent,
      pegylated liposomal doxorubicin has demonstrated similar efficacy to that of
      conventional doxorubicin in patients with metastatic breast cancer. It has also
      demonstrated efficacy in combination with other agents or modalities, including
      cyclophosphamide, paclitaxel, docetaxel, gemcitabine, vinorelbine, and
      hyperthermia. Response rates in patients with metastatic breast cancer receiving
      pegylated liposomal doxorubicin either alone or in combination regimens range
      from 27% to 83%, with median survival estimated at 7-20 months. Small studies
      also suggest a role for pegylated liposomal doxorubicin in the treatment of
      locally advanced breast cancer. Preliminary results suggest that pegylated
      liposomal doxorubicin may be safely administered in combination with docetaxel
      and trastuzumab in patients with HER2-positive disease. Owing to its comparable
      efficacy and favorable safety profile, pegylated liposomal doxorubicin may be a
      useful alternative to conventional doxorubicin, as well as other agents commonly
      used in the treatment of breast cancer.

PMID- 14715107
TI  - Trastuzumab regimens for HER2-overexpressing metastatic breast cancer.
AB  - Combination treatment with chemotherapy and trastuzumab is now standard therapy
      for the first-line treatment of women with HER2-overexpressing metastatic breast
      cancer. Combination therapy with trastuzumab has been shown to increase response
      rates, time to progression, quality of life, and overall survival for such
      patients. Several combination regimens have been developed, and newer combination
      regimens have recently been reported and are being studied in ongoing clinical
      trials. Newer trastuzumab-based regimens include triplet combinations with
      taxanes and platinum salts and regimens combining other innovative therapies.
      Among the increasing array of available combinations, several have proven
      appropriate for first-line therapy. To date, the optimal combination region has
      not been defined. Moreover, several questions remain regarding best scheduling,
      treatment duration, and use of trastuzumab at disease progression. This review
      briefly outlines the evolving role of trastuzumab in the treatment of HER2
      overexpressing metastatic breast cancer.

PMID- 14715109
TI  - Prognostic correlation of basic fibroblast growth factor and vascular endothelial
      growth factor in 1307 primary breast cancers.
AB  - This study was designed to investigate the possible relationship between the
      protein expression of basic fibroblast growth factor (bFGF) and vascular
      endothelial growth factor (VEGF) with p53 status, breast cancer prognostic
      factors, metastatic site, and survival after adjuvant therapy. Basic fibroblast
      growth factor and VEGF expression were determined by enzyme-linked immunosorbent
      assays in cytosol specimens obtained from 1307 patients with T1-3 primary breast
      cancer (789 node-negative, 518 node-positive) diagnosed between 1990 and 1997.
      The median follow-up time was 70 months. Increased bFGF expression was more
      frequently found in tumors with low VEGF expression (r = -0.286; P = 0.095).
      Increased bFGF was associated with smaller tumors (P < 0.001), absence of
      axillary metastasis (P = 0.003), low S-phase fraction (P < 0.001), and longer
      recurrence-free survival (RFS; P = 0.0038) and overall survival (OS; P = 0.0316).
      Vascular endothelial growth factor was a prognostic factor for RFS (P < 0.0001)
      and OS (P < 0.0001) in univariate and multivariate analyses (RFS: 95% CI, 1.1
      1.7; P = 0.036; OS: 95% CI, 1.2-2.2; P = 0.002), whereas bFGF expression was not
      correlated with RFS or OS. Increased VEGF content was correlated with shorter
      survival after adjuvant endocrine therapy (RFS, P = 0.0004; OS, P = 0.0009).
      Patients with estrogen receptor-negative disease were excluded from the analysis.
      Basic fibroblast growth factor was not a prognostic factor after adjuvant
      systemic therapy, nor was it related to metastatic site. Expression of VEGF is an
      independent prognostic factor for patients with primary breast cancer. High bFGF
      expression was related to good prognostic features and longer survival times, but
      did not add prognostic information in multivariate analysis. The results might
      implicate that different angiogenic pathways exist in human breast cancer.

PMID- 14715110
TI  - Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results.
AB  - Trastuzumab/chemotherapy combinations have already shown superior results in
      metastatic breast cancer patients. The purpose of this study is to determine the
      clinical efficacy of neoadjuvant trastuzumab and docetaxel in women with locally
      advanced breast cancer, with or without metastatic disease. Treatment-naive women
      with HER2-overexpressing locally advanced breast cancer, with or without
      metastatic disease, were included. Patients received trastuzumab 4 mg/kg loading
      dose intravenously then 2 mg/kg weekly. On day 22, docetaxel 100 mg/m2 every 3
      weeks for 4 cycles was added to weekly trastuzumab. Patients then underwent
      surgery and subsequent 4 cycles of AC (doxorubicin/cyclophosphamide; 60/600
      mg/m2) without trastuzumab. Weekly trastuzumab was resumed 1 month after
      completion of AC and continued for a year. Preliminary results from the first 22
      patients with median follow-up of 15.5 months (range, 2-38 months) are reported.
      Of these, 9 patients (40.9%) had inflammatory breast cancer, and 6 patients
      (27.3%) had stage IV breast cancer. Seventeen of 22 patients (77.3%) had
      objective clinical response, with a clinical complete response in 9 patients
      (40.9%). Two patients (9.1%) had decline in cardiac function and 7 patients
      (31.8%) experienced neutropenia, with 2 deaths (9.1%) from neutropenic sepsis.
      Eight patients (36.4%) have relapsed, 3 with local skin recurrence (13.6%) and 5
      with distant recurrence, of whom 1 had liver metastasis (4.5%) and 4 had brain
      metastasis (18.2%). Combined neoadjuvant trastuzumab and docetaxel induced high
      clinical response rates for HER2-overexpressing breast cancer, in particular for
      inflammatory breast cancer. A high rate of brain metastasis was noted,
      particularly in patients with baseline metastatic disease.

PMID- 14715111
TI  - Vascular endothelial growth factor-C and vascular endothelial growth factor-d
      messenger RNA expression in breast cancer: association with lymph node
      metastasis.
AB  - Lymph node metastasis is a major prognostic factor for patients with breast
      cancer. Vascular endothelial growth factors (VEGF)-C and VEGF-D are capable of
      stimulating lymphangiogenesis, and VEGF-C enhances lymphatic metastasis. The aim
      of the present study was to determine whether VEGF-C and VEGF-D messenger RNA
      (mRNA) expression is correlated with lymphatic invasion and lymph node metastasis
      in patients with breast cancer. Total RNAs were isolated from 33 surgical
      specimens of breast cancer tissue and 7 samples of normal breast tissue. VEGF-C
      and VEGF-D mRNA expression was measured by quantitative reverse transcription
      polymerase chain reaction analysis. There was no correlation between VEGF-C mRNA
      expression and lymphatic invasion or lymph node metastasis. However, VEGF-D mRNA
      expression was decreased in cancer tissue, and it was inversely correlated with
      lymphatic invasion and the number of metastatic lymph nodes. An increased VEGF
      C/VEGF-D ratio was also correlated with lymph node metastasis and the number of
      metastatic lymph nodes. Our results suggest that a decrease in VEGF-D mRNA or an
      increase in the VEGF-C/VEGF-D ratio may have an association with tumorigenesis
      and/or lymph node metastasis in breast cancer.

PMID- 14715112
TI  - A clinical trial of breast radiation therapy versus breast plus regional
      radiation therapy in early-stage breast cancer: the MA20 trial.

PMID- 14715113
TI  - Intergroup attitudes and attitudes towards devolution: field and laboratory
      experiments.
AB  - A field experiment provided the first test of the hypothesis that intergroup
      attitudes within a nation predict the group members' attitudes toward the break
      up of the nation. Prior to a referendum on the devolution of power from Britain
      to Wales, Welsh (minority) and English (majority) participants indicated their
      attitudes towards each other and towards devolution. As expected, there were
      significant correlations between intergroup attitudes and attitudes towards
      devolution, and these relations were different for Welsh vs. English
      participants. English respondents who held more positive attitudes towards Welsh
      people were significantly more favourable toward devolution, whereas Welsh
      respondents who held more positive attitudes towards English people were
      significantly less favourable towards devolution. A subsequent laboratory
      experiment provided a conceptual replication of this result, using manipulations
      of majority vs. minority status and of intergroup attitudes towards potentially
      devolving groups in psychology. These findings demonstrate that intergroup
      attitudes are highly relevant to understanding attitudes regarding devolution.

PMID- 14715114
TI  - Acting on intentions: the role of anticipated regret.
AB  - Three studies tested the hypothesis that anticipated regret (AR) increases
      consistency between exercise intentions and behaviour. Study 1 employed a
      longitudinal survey design (N = 384). Measures specified by the theory of planned
      behaviour, past behaviour, and AR were used to predict self-reported exercise
      behaviour 2 weeks later. AR moderated the intention-behaviour relationship such
      that participants were most likely to exercise if they both intended to exercise
      and anticipated regret if they failed to exercise. Study 2 used an experimental
      design to examine the effect of focusing on AR prior to reporting intentions (N =
      229). Exercise was measured 2 weeks later and the AR-focus manipulation was found
      to moderate the intention-behaviour relationship in a similar manner to that
      observed in Study 1. In Study 3 (N = 97), moderation was replicated and was shown
      to be mediated by the temporal stability of intention.

PMID- 14715115
TI  - Attitudes and evaluative practices: category vs. item and subjective vs.
      objective constructions in everyday food assessments.
AB  - In social psychology, evaluative expressions have traditionally been understood
      in terms of their relationship to, and as the expression of, underlying
      'attitudes'. In contrast, discursive approaches have started to study evaluative
      expressions as part of varied social practices, considering what such expressions
      are doing rather than their relationship to attitudinal objects or other putative
      mental entities. In this study the latter approach will be used to examine the
      construction of food and drink evaluations in conversation. The data are taken
      from a corpus of family mealtimes recorded over a period of months. The aim of
      this study is to highlight two distinctions that are typically obscured in
      traditional attitude work ('subjective' vs. 'objective' expressions, category vs.
      item evaluations). A set of extracts is examined to document the presence of
      these distinctions in talk that evaluates food and the way they are used and
      rhetorically developed to perform particular activities (accepting/refusing food,
      complimenting the food provider, persuading someone to eat). The analysis
      suggests that researchers (a) should be aware of the potential significance of
      these distinctions; (b) should be cautious when treating evaluative terms as
      broadly equivalent and (c) should be cautious when blurring categories and
      instances. This analysis raises the broader question of how far evaluative
      practices may be specific to particular domains, and what this specificity might
      consist in. It is concluded that research in this area could benefit from
      starting to focus on the role of evaluations in practices and charting their
      association with specific topics and objects.

PMID- 14715116
TI  - I feel for us: the impact of categorization and identification on emotions and
      action tendencies.
AB  - Building upon the social emotion model (Smith, 1999), we examined the combined
      impact of categorization context and social identification on emotional reactions
      and behavioural tendencies of people confronted with the victims of harmful
      behaviour. Depending on conditions, participants were led to categorize the
      victims and themselves in the same common group or in two distinct subgroups of
      the larger common group. We also measured participants' level of identification
      with the group that was made contextually salient. As predicted, emotional
      reactions of anger and their associated offensive action tendencies were more
      prevalent when participants were induced to see the victims and themselves as
      part of the same group and when they were highly identified with this common
      group. In line with appraisal theories of emotion, we also found that the
      emotional reaction fully mediated the impact of categorization context and
      identification on action tendencies. We discuss the data with respect to their
      implications for the role of emotion in improving intergroup relations.

PMID- 14715117
TI  - Space invaders: the moral-spatial order in neighbour dispute discourse.
AB  - This paper investigates the interactional construction of neighbour relationships
      in the context of disputational talk. Neighbour dispute data were recorded in two
      contexts: community mediation and televised documentaries. The data were
      transcribed and subsequently analysed using an approach that combined
      ethnomethodological methods with discursive psychology, focusing on participants'
      orientations to and constructions of spatial categories and place formulations.
      Three broad themes emerged from our analysis. First, we found that the
      construction and regulation of normative neighbour relationships were formulated
      in a discourse of spatial practice. Second, we found that, through complaints
      about spatial transgressions and 'good' and 'bad' neighbours, the moral order was
      reproduced and maintained. Finally, we found that, although participants were
      oriented to a distinction between 'private' and 'public' spaces, talk about
      boundaries revealed the highly contingent nature of spatial division. We suggest
      that in order to better understand neighbour relationships, social psychologists
      must explore the way people construct and account for the spaces they interact
      within.

PMID- 14715118
TI  - When group representations serve social change: the speeches of Patrice Lumumba
      during the Congolese decolonization.
AB  - This article examines how group representations can be used strategically to
      induce social change. The speeches delivered by Patrice Lumumba during the
      decolonization of the Belgian Congo were analysed using the content analysis
      software ALCESTE. Lumumba used radically different descriptions of Belgians and
      Congolese depending on the period during which the speech was delivered and on
      the audience he was addressing (Congolese or Belgian). When addressing Belgians,
      he described their countrymen as benevolent allies who could assist the
      development of Congo, and the Congolese as pacific and friendly. When addressing
      Congolese audiences, Belgians were described as oppressors, and Congolese as
      victims. In addition he emphasized the unity of the country more at the end of
      the decolonization process than at its onset. Considering that his nationalist
      and pan-African aims remained stable, we suggest that this variability stems from
      the different actions expected from his audiences, as a function of their group
      membership and the political context. We argue that this performative dimension
      cannot be captured if group representations, including stereotypes, are only
      viewed in cognitive terms. In addition, we show that they should be studied not
      only as justifications for the existing social order but also as instruments of
      social change.

PMID- 14715120
TI  - Feeling bad, but satisfied: the effects of upward and downward comparison upon
      mood and marital satisfaction.
AB  - This study in a sample of 135 women from rural areas examined the effects of
      social comparison with the marriage of another woman upon mood, identification
      and relationship evaluation. The comparison target constituted either an upward
      or a downward comparison, characterized by either high or low effort. Upward
      targets evoked a more positive mood, and a less negative mood than downward
      targets, while, in contrast, the evaluation of one's own relationship was more
      positive after being exposed to a downward target than after being exposed to an
      upward target. Upward targets and high-effort targets instilled more
      identification than downward and low-effort targets. A higher level of marital
      quality led to less identification with the downward targets and to more
      identification with the upward targets, particularly with targets who put a high
      degree of effort in the relationship. Identification mediated the association
      between marital quality and positive mood following upward comparison. The
      present study suggests that upward and downward comparison may have effects upon
      mood that are opposite to those upon self-evaluation, and demonstrates that
      happily married individuals may through identification with upward targets derive
      positive affective consequences from exposure to such targets.

PMID- 14715119
TI  - Committed to (un)equal opportunities?: 'New ageism' and the older worker.
AB  - In recent years the principle of equality of opportunity in employment has been
      widely promoted as a means of addressing the marginalization of various groups of
      workers, including older workers. Evidence suggests, however, that equal
      opportunities have not improved prospects for older workers. The present study
      employs discourse analysis to examine a variety of accounts of those responsible
      for employment within a number of organizations. Analysis shows that these
      accounts are rhetorically oriented towards potential attributions of age
      discrimination. As evidence of a non-discriminatory stance, participants attend
      to possible shortcomings in written policies by making explicit their
      organizations' equal opportunity practices. In describing their workforces as
      comprising predominantly younger employees, however, they make only implicit
      reference to practices involving older workers. When they account for the
      apparent age imbalances in their workforces, they attribute these imbalances to
      factors outwith their control so that the organization's practices become
      completely 'invisible'. The contrast between this 'invisibility' and explicit
      claims to be committed to equal opportunities allows participants to position
      themselves as non-discriminating employers and at the same time justifies the
      marginalization of older workers.

PMID- 14715121
TI  - Ethical issues of "case" reports: what can we learn from case studies?

PMID- 14715123
TI  - Frequency of newborn behaviours associated with neonatal abstinence syndrome: a
      hospital-based study.
AB  - OBJECTIVES: To determine the frequency of neonatal abstinence syndrome (NAS)
      among unselected term newborns, using newborn behaviour data only. METHODS: This
      hospital-based prospective exploratory study used clinical observations of
      newborn behaviours, mothers' observations of their newborns, and newborn chart
      data to determine the prevalence of suspected and confirmed cases of NAS in a
      convenience sample of unselected term newborns "rooming in" with their mothers in
      a large central city acute-care referral hospital. Over a 4-month period, 824 out
      of 1008 newborns were observed at between 8 and 30 hours of life by specially
      trained nurse observers. Behaviours recorded and their weighting were adapted
      from the Neonatal Abstinence Scoring System (NASS) by Finnegan and Kaltenbach.
      Newborns with scores of 5 or greater and "suspect for NAS" were referred to their
      physicians for confirmation or refutation of the clinical findings. The
      prevalence of "suspect for NAS" and confirmed NAS, as well as of individual
      neonatal behaviours, was calculated. RESULTS: Thirty-one (3.8%) of 824 term
      "rooming in" newborns were identified with findings suggestive of NAS. Four
      newborns were positively identified as having NAS and treated. The identification
      was confirmed by post hoc affirmation of maternal drug use. Individual behaviours
      occurring in 10% or more of newborns included excessive sneezing, nasal
      stuffiness, unsustained suck, tremor, and abnormal nipple latch. CONCLUSIONS:
      Clinical observation of newborn behaviour may identify NAS. Further studies are
      recommended to correlate this methodology with laboratory findings, as are more
      in-depth maternal questionnaires concerning use of mood-altering substances. The
      prevalence of NAS is likely underestimated because of early hospital discharge. A
      coordinated system of early identification and infant-specific assessment and
      treatment, both in hospital and following discharge home, is advocated.

PMID- 14715122
TI  - Ovarian follicular development during the use of oral contraception: a review.
AB  - Over the past 40 years, alterations to the composition of oral contraceptives
      (OCs) have been made in attempts to reduce adverse effects and to improve patient
      compliance while maintaining contraceptive efficacy. However, there is growing
      evidence to indicate that reducing the estrogen dose to minimize adverse effects
      may have compromised the degree of hypothalamo-pituitary-ovarian suppression,
      particularly during the hormone-free interval (HFI) or following missed doses.
      Follicle development during OC use appears to occur in association with a loss of
      endocrine suppression during the HFI. This information provides a rationale for
      reducing or eliminating the HFI in OC regimens. There is also evidence for an
      increased risk of follicle development and ovulation in women who use delayed OC
      initiation schemes, such as the "Sunday Start" method. It is not currently known
      why some follicles ovulate during OC use while others regress or form anovulatory
      follicle cysts. Continued research about follicle development during OC use would
      provide insight into understanding the precise mechanisms of action underlying
      combined OCs, as well as those of continuous OC formulations and emergency
      contraceptive regimens.

PMID- 14715124
TI  - Managing obstetrical patients during severe acute respiratory syndrome outbreak.
AB  - Severe Acute Respiratory Syndrome (SARS) is a newly described infectious disease
      caused by a coronavirus. Two outbreaks occurred in Toronto in the spring of 2003,
      resulting in the closure of 3 hospitals, including 2 obstetrical units.
      Strategies, devised using information about the coronavirus available at the
      time, as well as epidemiologic and infectious disease containment measures, were
      initiated to protect obstetrical patients and staff. In the first outbreak, the
      obstetrical unit of an affected Toronto hospital was kept open while other
      clinical services were closed. In the second outbreak, the obstetrical unit was
      closed along with all other clinical activities. This report details the stepwise
      processes used to make decisions during the SARS outbreaks and the implementation
      of the decisions made. It is recommended that these or similar protocols be used
      when an obstetrical unit is confronted with a large-scale nosocomial infectious
      outbreak that has a mechanism of transmission similar to that of SARS.

PMID- 14715125
TI  - Informed consent in the (mis)information age.
AB  - Recent studies suggest that large numbers of health-care consumers are turning to
      the Internet as a source of health information. This article considers the
      potential impact of on-line health information on women's health-care decisions,
      and the role of physicians relating to their patients' use of the Internet as an
      information source. In particular, the article examines the effect of on-line
      health information on the informed consent process. Physicians' disclosure
      obligations (their legal duty to provide information to patients) and the law of
      informed consent are briefly described. The article then considers the Internet
      as a source of health information, and instances and types of misinformation.
      Finally, the article suggests steps physicians may take to help their patients
      benefit from Internet health information and to become critical consumers who do
      not fall victim to inaccurate or misleading information. The article concludes by
      suggesting that physicians make a practice of asking their patients about
      alternate sources of information they may have accessed, in order to help ensure
      that patients' health-care decisions are based on current, accurate, and complete
      information.

PMID- 14715126
TI  - Use of hormonal replacement therapy after treatment of breast cancer.
AB  - OBJECTIVE: To review the use of hormonal replacement therapy (HRT) after
      treatment of breast cancer. OPTIONS: The effect and role of estrogens on breast
      cancer. OUTCOME: Improved health and quality of life for women with breast
      cancer. VALUES: References were collected through MEDLINE searches up to 2002.
      EVIDENCE: The level of evidence and quality of recommendations have been
      determined using the criteria described by the Canadian Task Force on the
      Periodic Health Examination. BENEFITS, HARMS, AND COSTS: Utilization of the
      information to make a proper risk-benefit assessment of HRT use in women with
      breast cancer. RECOMMENDATIONS: 1. HRT after treatment of breast cancer has not
      been demonstrated to have an adverse impact on recurrence and mortality.(II-2B)
      2. HRT is an option in postmenopausal women with previously treated breast
      cancer.(II-2B) 3. Prospective, randomized clinical trial results are needed.(III
      A) VALIDATION: Recommendations were reviewed and revised by the Breast Disease
      Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and
      approved by the Executive and Council of the SOGC. SPONSOR: The Society of
      Obstetricians and Gynaecologists of Canada.

PMID- 14715127
TI  - Long life: a matter of taste (and smell).
AB  - Insulin/IGF signaling has emerged as a central regulator of metazoan aging. In C.
      elegans, insulin-like peptides are expressed predominately in neurons. Alcedo and
      Kenyon demonstrate that removal of specific gustatory and olfactory neurons
      result in longer life, suggesting that metazoan longevity is influenced by
      sensory perception.

PMID- 14715128
TI  - Splicing it up: a variant of the N-type calcium channel specific for pain.
AB  - How would you make a drug that inhibits pain without side effects? The most
      obvious strategy for analgesia targets molecules that are expressed only on
      neurons used for pain. In this issue of Neuron, Bell et al. report a new splice
      variant of a calcium channel that controls neurotransmitter release and show that
      it is expressed primarily on nociceptors, the sensory neurons that trigger pain.

PMID- 14715129
TI  - A constraint on cAMP signaling.
AB  - Studies in invertebrates and vertebrates have demonstrated a critical role for
      cAMP signaling and adenylyl cyclase (AC) activity in learning and memory. In this
      issue of Neuron, Pineda et al. show that in the hippocampus, reduction of AC
      activity via the inhibitory G protein G(i) is critical for memory formation,
      suggesting that a balance of inhibitory and stimulatory regulators of AC is
      required for optimal cAMP signaling.

PMID- 14715130
TI  - Cholesterol and the biology of Alzheimer's disease.
AB  - Recent results implicating cholesterol metabolism in the pathophysiology of
      Alzheimer's disease (AD) bring cholesterol to the forefront of AD research.
      Research from genetics, epidemiology, and cell biology all converge, suggesting
      that cholesterol plays a central role in the biology of amyloid precursor protein
      and the toxic peptide generated by its cleavage, beta-amyloid (Abeta). The
      ability of cholesterol to modulate Abeta production suggests opportunities for
      therapeutic intervention, although the functional significance underlying the
      connection between cholesterol and Abeta remains to be investigated.

PMID- 14715131
TI  - The neural basis of hyperlexic reading: an FMRI case study.
AB  - Children with autism spectrum disorders in very rare cases display surprisingly
      advanced "hyperlexic" reading skills. Using functional magnetic resonance imaging
      (fMRI), we studied the neural basis of this precocious reading ability in a 9
      year-old hyperlexic boy who reads 6 years in advance of his age. During covert
      reading, he demonstrated greater activity in the left inferior frontal and
      superior temporal cortices than both chronological age- and reading age-matched
      controls. Activity in the right inferior temporal sulcus was greater when
      compared to reading age-matched controls. These findings suggest that precocious
      reading is brought about by simultaneously drawing on both left hemisphere
      phonological and right hemisphere visual systems, reconciling the two prevailing,
      but seemingly contradictory, single hemisphere theories of hyperlexia. Hyperlexic
      reading is therefore associated with hyperactivation of the left superior
      temporal cortex, much in the same way as developmental dyslexia is associated
      with hypoactivation of this area.

PMID- 14715132
TI  - BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse
      model of Alzheimer's disease.
AB  - beta-site APP cleaving enzyme 1 (BACE1) is the beta-secretase enzyme required for
      generating pathogenic beta-amyloid (Abeta) peptides in Alzheimer's disease (AD).
      BACE1 knockout mice lack Abeta and are phenotypically normal, suggesting that
      therapeutic inhibition of BACE1 may be free of mechanism-based side effects.
      However, direct evidence that BACE1 inhibition would improve cognition is
      lacking. Here we show that BACE1 null mice engineered to overexpress human APP
      (BACE1(-/-).Tg2576(+)) are rescued from Abeta-dependent hippocampal memory
      deficits. Moreover, impaired hippocampal cholinergic regulation of neuronal
      excitability found in the Tg2576 AD model is ameliorated in BACE1(-/-).Tg2576(+)
      bigenic mice. The behavioral and electrophysiological rescue of deficits in
      BACE1(-/-).Tg2576(+) mice is correlated with a dramatic reduction of cerebral
      Abeta40 and Abeta42 levels and occurs before amyloid deposition in Tg2576 mice.
      Our gene-based approach demonstrates that lower Abeta levels are beneficial for
      AD-associated memory impairments, validating BACE1 as a therapeutic target for
      AD.

PMID- 14715133
TI  - Extensive and divergent effects of sleep and wakefulness on brain gene
      expression.
AB  - Sleep is present in all species where it has been studied, but its functions
      remain unknown. To investigate what benefits sleep may bring at the cellular
      level, we profiled gene expression in awake and sleeping rats by using high
      density microarrays. We find that approximately 10% of the transcripts in the
      cerebral cortex change their expression between day and night and demonstrate
      that half of them are modulated by sleep and wakefulness independent of time of
      day. We also show that molecular correlates of sleep are found in the cerebellum,
      a structure not known for generating sleep rhythms. Finally, we show that
      different functional categories of genes are selectively associated with sleep
      and wakefulness. The approximately 100 known genes whose expression increases
      during sleep provide molecular support for the proposed involvement of sleep in
      protein synthesis and neural plasticity and point to a novel role for sleep in
      membrane trafficking and maintenance.

PMID- 14715134
TI  - Regulation of C. elegans longevity by specific gustatory and olfactory neurons.
AB  - The life span of C. elegans is extended by mutations that inhibit the function of
      sensory neurons. In this study, we show that specific subsets of sensory neurons
      influence longevity. We find that certain gustatory neurons inhibit longevity,
      whereas others promote longevity, most likely by influencing insulin/IGF-1
      signaling. Olfactory neurons also influence life span, and they act in a distinct
      pathway that involves the reproductive system. In addition, we find that a
      putative chemosensory G protein-coupled receptor that is expressed in some of
      these sensory neurons inhibits longevity. Together our findings imply that the
      life span of C. elegans is regulated by environmental cues and that these cues
      are perceived and integrated in a complex and sophisticated fashion by specific
      chemosensory neurons.

PMID- 14715135
TI  - SPARC-like 1 regulates the terminal phase of radial glia-guided migration in the
      cerebral cortex.
AB  - Differential adhesion between migrating neurons and transient radial glial fibers
      enables the deployment of neurons into appropriate layers in the developing
      cerebral cortex. The identity of radial glial signals that regulate the
      termination of migration remains unclear. Here, we identified a radial glial
      surface antigen, SPARC (secreted protein acidic and rich in cysteine)-like 1,
      distributed predominantly in radial glial fibers passing through the upper strata
      of the cortical plate (CP) where neurons end their migration. Neuronal migration
      and adhesion assays indicate that SPARC-like 1 functions to terminate neuronal
      migration by reducing the adhesivity of neurons at the top of the CP. Cortical
      neurons fail to achieve appropriate positions in the absence of SPARC-like 1
      function in vivo. Together, these data suggest that antiadhesive signaling via
      SPARC-like 1 on radial glial cell surfaces may enable neurons to recognize the
      end of migration in the developing cerebral cortex.

PMID- 14715136
TI  - Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1
      pathway.
AB  - Reelin is a secreted glycoprotein that regulates neuronal positioning in cortical
      brain structures through the VLDLR and ApoER2 receptors and the adaptor protein
      Dab1. In addition to cellular disorganization, dendrite abnormalities are present
      in the brain of reeler mice lacking Reelin. It is unclear whether these defects
      are due primarily to cellular ectopia or the absence of Reelin. Here we examined
      dendrite development in the hippocampus of normal and mutant mice and in
      dissociated cultures. We found that dendrite complexity is severely reduced in
      homozygous mice deficient in Reelin signaling both in vivo and in vitro, and it
      is also reduced in heterozygous mice in the absence of cellular ectopia. Addition
      of Reelin interfering antibodies, receptor antagonists, and Dab1 phosphorylation
      inhibitors prevented dendrite outgrowth from normal neurons, whereas addition of
      recombinant Reelin rescued the deficit in reeler cultures. Thus, the same
      signaling pathway controls both neuronal migration and dendrite maturation.

PMID- 14715137
TI  - N-glycosylation is essential for vesicular targeting of synaptotagmin 1.
AB  - Synaptotagmins 1 and 7 are candidate Ca(2+) sensors for exocytosis localized to
      synaptic vesicles and plasma membranes, respectively. We now show that the N
      terminal intraluminal sequence of synaptotagmin 1, when transplanted onto
      synaptotagmin 7, redirects synaptotagmin 7 from the plasma membrane to secretory
      vesicles. Conversely, mutation of the N-terminal N-glycosylation site of
      synaptotagmin 1 redirects synaptotagmin 1 from vesicles to the plasma membrane.
      In cultured hippocampal neurons, the plasma membrane-localized mutant of
      synaptotagmin 1 suppressed the readily releasable pool of synaptic vesicles,
      whereas wild-type synaptotagmin 1 did not. In addition to the intraluminal N
      glycosylation site, the cytoplasmic C(2) domains of synaptotagmin 1 were required
      for correct targeting but could be functionally replaced by the C(2) domains of
      synaptotagmin 7. Our data suggest that the intravesicular N-glycosylation site of
      synaptotagmin 1 collaborates with its cytoplasmic C(2) domains in directing
      synaptotagmin 1 to synaptic vesicles via a novel N-glycosylation-dependent
      mechanism.

PMID- 14715138
TI  - Ca2+ influx through distinct routes controls exocytosis and endocytosis at
      drosophila presynaptic terminals.
AB  - Endocytosis of synaptic vesicles follows exocytosis, and both processes require
      external Ca(2+). However, it is not known whether Ca(2+) influx through one route
      initiates both processes. At larval Drosophila neuromuscular junctions, we
      separately measured exocytosis and endocytosis using FM1-43. In a temperature
      sensitive Ca(2+) channel mutant, cacophony(TS2), exocytosis induced by high K(+)
      decreased at nonpermissive temperatures, while endocytosis remained unchanged. In
      wild-type larvae, a spider toxin, PLTXII, preferentially inhibited exocytosis,
      whereas the Ca(2+) channel blockers flunarizine and La(3+) selectively depressed
      endocytosis. None of these blockers affected exocytosis or endocytosis induced by
      a Ca(2+) ionophore. Evoked synaptic potentials were depressed regardless of
      stimulus frequency in cacophony(TS2) at nonpermissive temperatures and in wild
      type by PLTXII, whereas flunarizine or La(3+) gradually depressed synaptic
      potentials only during high-frequency stimulation, suggesting depletion of
      synaptic vesicles due to blockade of endocytosis. In shibire(ts1), a dynamin
      mutant, flunarizine or La(3+) inhibited assembly of clathrin at the plasma
      membrane during stimulation without affecting dynamin function.

PMID- 14715139
TI  - Maintenance of high-frequency transmission at purkinje to cerebellar nuclear
      synapses by spillover from boutons with multiple release sites.
AB  - Cerebellar Purkinje neurons maintain high firing rates but their synaptic
      terminals depress only moderately, raising the question of how vesicle depletion
      is minimized. To identify mechanisms that limit synaptic depression, we evoked
      100 Hz trains of GABAergic inhibitory postsynaptic currents (IPSCs) in cerebellar
      nuclear neurons by stimulating Purkinje axons in mouse brain slices. The paired
      pulse ratio (IPSC(2)/IPSC(1)) of the total IPSC was approximately 1 and the
      steady-state ratio (IPSC(20)/IPSC(1)) was approximately 0.5, suggesting a high
      response probability of postsynaptic receptors, without an unusually high release
      probability. Three-dimensional electron microscopic reconstructions of Purkinje
      boutons revealed multiple active zones without intervening transporters,
      suggestive of "spillover"-mediated transmission. Simulations of boutons with 10
      16 release sites, in which transmitter from any site can reach all receptors
      opposite the bouton, replicated multiple-pulse depression during normal, high,
      and low presynaptic Ca influx. These results suggest that release from multiple
      site boutons limits depletion-based depression, permitting prolonged, high
      frequency inhibition at corticonuclear synapses.

PMID- 14715140
TI  - Cell-specific alternative splicing increases calcium channel current density in
      the pain pathway.
AB  - N-type calcium channels are critical for pain transduction. Inhibitors of these
      channels are powerful analgesics, but clinical use of current N-type blockers
      remains limited by undesirable actions in other regions of the nervous system. We
      now demonstrate that a unique splice isoform of the N-type channel is restricted
      exclusively to dorsal root ganglia. By a combination of functional and molecular
      analyses at the single-cell level, we show that the DRG-specific exon, e37a, is
      preferentially present in Ca(V)2.2 mRNAs expressed in neurons that contain
      nociceptive markers, VR1 and Na(V)1.8. Cell-specific inclusion of exon 37a
      correlates closely with significantly larger N-type currents in nociceptive
      neurons. This unique splice isoform of the N-type channel could represent a novel
      target for pain management.

PMID- 14715141
TI  - Glutamate uptake determines pathway specificity of long-term potentiation in the
      neural circuitry of fear conditioning.
AB  - Long-term synaptic modifications in afferent inputs to the amygdala underlie fear
      conditioning in animals. Fear conditioning to a single sensory modality does not
      generalize to other cues, implying that synaptic modifications in fear
      conditioning pathways are input specific. The mechanisms of pathway specificity
      of long-term potentiation (LTP) are poorly understood. Here we show that
      inhibition of glutamate transporters leads to the loss of input specificity of
      LTP in the amygdala slices, as assessed by monitoring synaptic responses at two
      independent inputs converging on a single postsynaptic neuron. Diffusion of
      glutamate ("spillover") from stimulated synapses, paired with postsynaptic
      depolarization, is sufficient to induce LTP in the heterosynaptic pathway,
      whereas an enzymatic glutamate scavenger abolishes this effect. These results
      establish active glutamate uptake as a crucial mechanism maintaining the pathway
      specificity of LTP in the neural circuitry of fear conditioning.

PMID- 14715142
TI  - Removal of G(ialpha1) constraints on adenylyl cyclase in the hippocampus enhances
      LTP and impairs memory formation.
AB  - Stimulation of adenylyl cyclase in the hippocampus is critical for memory
      formation. However, generation of cAMP signals within an optimal range for memory
      may require a balance between stimulatory and inhibitory mechanisms. The role of
      adenylyl cyclase inhibitory mechanisms for memory has not been addressed. One of
      the mechanisms for inhibition of adenylyl cyclase is through activation of G(i)
      coupled receptors, a mechanism that could serve as a constraint on memory
      formation. Here we report that ablation of G(ialpha1) by gene disruption
      increases hippocampal adenylyl cyclase activity and enhances LTP in area CA1.
      Furthermore, gene ablation of G(ialpha1) or antisense oligonucleotide-mediated
      depletion of G(ialpha1) disrupted hippocampus-dependent memory. We conclude that
      G(ialpha1) provides a critical mechanism for tonic inhibition of adenylyl cyclase
      activity in the hippocampus. We hypothesize that loss of G(ialpha1) amplifies the
      responsiveness of CA1 postsynaptic neurons to stimuli that strengthen synaptic
      efficacy, thereby diminishing synapse-specific plasticity required for new memory
      formation.

PMID- 14715143
TI  - Neuronal correlates of a perceptual decision in ventral premotor cortex.
AB  - The ventral premotor cortex (VPC) is involved in the transformation of sensory
      information into action, although the exact neuronal operation is not known. We
      addressed this problem by recording from single neurons in VPC while trained
      monkeys report a decision based on the comparison of two mechanical vibrations
      applied sequentially to the fingertips. Here we report that the activity of VPC
      neurons reflects current and remembered sensory inputs, their comparison, and
      motor commands expressing the result; that is, the entire processing cascade
      linking the evaluation of sensory stimuli with a motor report. These findings
      provide a fairly complete panorama of the neural dynamics that underlies the
      transformation of sensory information into an action and emphasize the role of
      VPC in perceptual decisions.

PMID- 14715144
TI  - Differential effects of the sleep-inducing lipid oleamide and cannabinoids on the
      induction of long-term potentiation in the CA1 neurons of the rat hippocampus in
      vitro.
AB  - Cannabinoids have been shown to impair cognition in vivo and block long-term
      potentiation (LTP), a candidate experimental model of learning and memory in
      vitro, via cannabinoid receptor (CB1) activation. cis-Oleamide (cOA) is an
      endogenous sleep-inducing lipid with putative cannabinomimetic properties. We
      hypothesise that cOA is cannabinomimetic and perform a comparative study with
      synthetic and endogenous cannabinoids on their effects on synaptic conditioning
      via two different patterns of stimulation in the hippocampal slice. CB1 agonists,
      R(+)-WIN55212-2 and anandamide, but not cOA blocked high frequency stimulation
      (HFS)-LTP. R(+)-WIN55212-2 and cOA (stereoselectively) attenuated responses to
      theta-burst-LTP, while anandamide did not. The anandamide transport inhibitor,
      AM404, attenuated HFS-LTP, an effect reversed by the CB1 receptor antagonist
      SR141716A but not mimicked by the vanilloid receptor agonist capsaicin. TFNO, an
      inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for
      degrading anandamide, failed to block HFS-LTP alone or in combination with cOA.
      On the contrary, this combination was as effective as cOA on its own in
      attenuating theta-burst-LTP. cOA effects on theta-burst-LTP were prevented in the
      presence of the GABA(A) receptor blocker picrotoxin, but not by pretreatment with
      SR141716A. These findings suggest that cOA neither directly activates CB1
      receptors nor acts via the proposed "entourage" effect [Nature 389 (1997) 25] to
      increase titres of anandamide through FAAH inhibition. The selective effects of
      cOA on theta-burst-conditioning may reflect modulation of GABAergic transmission.
      Anandamide uptake inhibition, but not blockade of FAAH, effectively increases
      synaptic concentrations of endocannabinoids.

PMID- 14715145
TI  - Extension of cerebral hypoperfusion and ischaemic pathology beyond MCA territory
      after intraluminal filament occlusion in C57Bl/6J mice.
AB  - Rodent models of focal cerebral ischaemia are critical for understanding
      pathophysiological concepts in human stroke. The availability of genetically
      modified mice has prompted the adaptation of the intraluminal filament occlusion
      model of focal ischaemia for use in mice. In the present study, we investigated
      the effects of increasing duration of intraluminal occlusion on the extent and
      distribution of ischaemic pathology and local cerebral blood flow (LCBF) in
      C57Bl/6J mice, the most common background mouse strain. Volumetric assessment of
      ischaemic damage was performed after 15, 30 or 60 min occlusion followed by 24 h
      reperfusion. LCBF was measured after 15 and 60 min occlusion using quantitative
      14C-iodoantipyrine autoradiography. The extent and distribution of ischaemic
      damage was highly sensitive to increasing occlusion duration. Recruitment of
      tissue outside MCA territory produced a steep increase in the volume of damage
      with increasing occlusion duration: 15 min (9+/-2 mm3); 30 min (56+/-6 mm3); 60
      min (69+/-2 mm3). Significant increases in the severity of cerebral hypoperfusion
      were observed after 60 min compared to 15 min occlusion within and outside MCA
      territory, e.g. caudate nucleus (9+/-6 ml per 100 g per min at 60 min vs. 33 ml
      per 100 g per min at 15 min) and hippocampus (16+/-14 ml per 100 g per min at 60
      min vs. 61+/-16 ml per 100 g per min at 15 min). MABP remained stable for 25 min
      after occlusion onset and declined thereafter. The integrity of the circle of
      Willis was examined by carbon black perfusion of the vasculature. A complete
      circle of Willis was present in only one of 10 mice. These results demonstrate
      that intraluminal filament occlusion in C57Bl/6J mice leads to an occlusion
      duration-dependent increase in severity of cerebral hypoperfusion and extension
      of ischaemic pathology beyond MCA territory.

PMID- 14715146
TI  - Distribution of nociceptin/orphanin FQ in adult human brain.
AB  - Nociceptin/orphanin FQ (N/OFQ), the endogenous agonist for the opioid receptor
      like receptor 1 (ORL1), shows significant similarities to dynorphin A in
      structure and distribution in rat central nervous system. The distribution of
      N/OFQ in human brain has not been studied. We measured the concentrations of
      N/OFQ in 47 microdissected areas of the central nervous system of adult human
      brain using radioimmunoassay (RIA). Significant heterogeneity was found in the
      levels of N/OFQ concentration in the various analyzed regions. The highest
      concentrations were measured in the dorsal central gray matter (periaqueductal
      gray), the locus coeruleus, the ventromedial nucleus of hypothalamus, the septum
      and the dorsal horn of the spinal cord. High concentrations were also detected in
      other hypothamamic nuclei, the inferior colliculus, the ventral central gray
      matter, the pontine tegmentum, the amygdala, the reticular formation and the
      spinal trigeminal nucleus. Considerable similarity with the distribution of N/OFQ
      in rat CNS was observed. The widespread distribution in CNS predicts multifaceted
      functions for N/OFQ.

PMID- 14715147
TI  - The effects of ciliary neurotrophic factor on neurological function and glial
      activity following contusive spinal cord injury in the rats.
AB  - Ciliary neurotrophic factor (CNTF) has been implicated in the pathophysiology of
      injury to the central nervous system. The rapid increase in CNTF production
      following spinal cord injury (SCI) in rats is thought to serve a role in the
      neuronal survival and functional recovery. In this study, 40 SD rats were divided
      into four groups: sham-operated group, saline-treated group, 5- and 10-microg
      CNTF group. Saline and CNTF were given through lumbar intrathecal catheter for 10
      days after T10 segment of spinal cord were injured by modified Allen contusion
      method. Animals were behaviorally tested for 6 weeks using the Basso, Beattie,
      Bresnahan locomotor rating scale and inclined plane test. At the end of 6 week,
      rubrospinal neurons of five rats in each group were labeled by retrograde
      transport of the horseradish peroxidase (HRP) from the lesion site, and then the
      labeled red nucleus neuron (RN) numbers were counted. Additional rats were
      histologically assessed for tissue sparing and neuronal loss and reactive gliosis
      at the injury site and adjacent areas. Rats treated with CNTF regained greater
      improvements in hindlimb function than controls. The amount of spared tissue was
      significantly higher in CNTF-treated animals than in controls. After CNTF
      treatment, the number of HRP-labeled RN neurons were significantly increased.
      Astrocytes and microglia reactivity was more pronounced in CNTF-treated animals
      than in controls. These results indicate that intrathecal infusion of exogenous
      CNTF following SCI may significantly reduce tissue damage and protect the
      rubrospinal descending tracks and enhances functional recovery, and may also
      induce more gliosis.

PMID- 14715148
TI  - Time course of efferent fiber and spiral ganglion cell degeneration following
      complete hair cell loss in the chinchilla.
AB  - Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as
      gentamicin (GM). In the chinchilla, co-administration of GM and EA can produce
      hair cell lesions ranging from a small loss of outer hair cells (OHCs) in the
      base of the cochlea to complete destruction of all hair cells, depending on
      dosing parameters. Although hair cell loss has been characterized, little is
      known about the fate of efferent fibers or spiral ganglion neurons (SGNs) in this
      model. To study the time course of efferent fiber and SGN loss, chinchillas were
      injected with GM (125 mg/kg IM) followed immediately by EA (40 mg/kg IV).
      Estimates of efferent fiber loss and density changes were made after 3 days or 1,
      2, 3, or 4 weeks of survival. Estimates of SGN loss and density changes were made
      after 15 days or 1, 2, 4, or 6 months of survival. Cochlear function was rapidly
      abolished and all cochlear hair cells were missing within 24 h after treatment.
      Inner hair cells (IHCs) in the middle turn of the cochlea died earlier than cells
      in the apex or base, and OHCs in Rows 1 and 2 died earlier than OHCs in Row 3.
      Degeneration of efferent nerve fibers began 3-7 days post-injection, versus 15-30
      days for SGNs, and the loss of efferent fibers was essentially complete within 1
      month, versus 2-4 months for SGNs. The rapid time course of efferent fiber and
      SGN loss in the chinchilla may make it a practical model for studying mechanisms
      of neural loss and survival in the mammalian inner ear.

PMID- 14715149
TI  - Functional characterization of brain peptide transporter in rat cerebral cortex:
      identification of the high-affinity type H+/peptide transporter PEPT2.
AB  - In this report, we studied the functional characteristics of a brain peptide
      transporter using synaptosomes prepared from rat cerebral cortex. Crude
      synaptosomes (P(2) fraction) were prepared from cerebral cortices in male Wistar
      rats. Uptake of [14C]glycylsarcosine (Gly-Sar), a substrate for H(+)/oligopeptide
      transporters PEPT1 and PEPT2, and [3H]histidine, a substrate for
      peptide/histidine transporters PHT1 and PHT2, was measured at 37 degrees C by a
      rapid filtration technique. The uptake of [14C]Gly-Sar into synaptosomes was
      stimulated by an inwardly directed H(+)-gradient. The uptake system exhibited a
      Michaelis-Menten constant (K(t)) of 110+/-20 microM for Gly-Sar. This value is
      comparable to the K(t) value for Gly-Sar uptake via the high-affinity
      H(+)/peptide transporter PEPT2. The H(+)-dependent uptake of [14C]Gly-Sar into
      synaptosomes was inhibited by di- and tripeptides and beta-lactam antibiotics,
      but was unaffected by amino acids glycine and histidine. In particular,
      kyotorphin (Tyr-Arg) completely inhibited Gly-Sar uptake with the K(i) value of
      29+/-14 microM. These uptake properties of the brain peptide transporter (i.e.,
      the K(t) value for Gly-Sar uptake and the K(i) value of kyotorphin for Gly-Sar
      uptake) are very similar to those of PEPT2. RT-PCR and Western blotting analyses
      revealed that PEPT2 is actually expressed in the cerebral cortex in rat. These
      results indicate that a H(+)-coupled high affinity peptide transport system is
      functionally expressed in the cerebral cortex and that this transport system is
      identical to PEPT2.

PMID- 14715150
TI  - Gamma-hydroxybutyrate and ethanol depress spontaneous excitatory postsynaptic
      currents in dopaminergic neurons of the substantia nigra.
AB  - Gamma-hydroxybutyrate (GHB) has been shown to have therapeutical properties in
      various psychiatric disorders, especially in alcohol abuse, and to mimic
      different actions of ethanol at the cellular and system level. Using whole-cell
      patch-clamp recordings on brain slices of 21- to 25-day-old rats, the present
      study investigated the effects of GHB and ethanol on spontaneous excitatory
      postsynaptic currents (sEPSCs) in dopaminergic neurons of the substantia nigra
      pars compacta (SNc). sEPSCs are an index of glutamate release from the excitatory
      input to dopamine cells, which play a key role in different reward-related
      behaviors. We found that GHB and ethanol depressed both the frequency and the
      amplitude of sEPSCs. These effects were GABA(B)-independent and the GHB-induced
      depression was blocked by the GHB receptor antagonist 6,7,8,9-tetrahydro
      5[H]benzocyclohepte-5-ol-4-ylidene acetic acid (NCS-382), pointing to a specific
      effect of this drug. The effects of ethanol were not affected by NCS-382. This
      study indicates that GHB and ethanol share the effect of reducing the efficacy of
      excitatory glutamatergic neurotransmission in the SNc by acting through different
      mechanisms.

PMID- 14715151
TI  - Activation of mu-opioid receptors excites a population of locus coeruleus-spinal
      neurons through presynaptic disinhibition.
AB  - The nucleus locus coeruleus (LC) plays an important role in analgesia produced by
      opioids and by modulation of the descending noradrenergic pathway. The functional
      role of micro-opioid receptors (muOR) in regulation of the excitability of
      spinally projecting LC neurons has not been investigated. In the present study,
      we tested the hypothesis that activation of presynaptic mu-opioid receptors
      excites a population of spinally projecting LC neurons through attenuation of
      gamma-aminobutyric acid (GABA)-ergic synaptic inputs. Spinally projecting LC
      neurons were retrogradely labeled by a fluorescent dye injected into the spinal
      dorsal horn of rats. Whole-cell current- and voltage-clamp recordings were
      performed on labeled LC neurons in brain slices. All labeled LC noradrenergic
      neurons were demonstrated by dopamine-beta-hydroxylase (DbetaH)
      immunofluorescence. In 37 labeled LC neurons, (D-Ala(2),N-Me-Phe(4),Gly-ol(5))
      enkephalin (DAMGO) significantly increased the discharge activity of 17 (45.9%)
      neurons, but significantly inhibited the firing activity of another 15 (40.5%)
      cells. The excitatory effect of DAMGO on seven labeled LC neurons was diminished
      in the presence of bicuculline. DAMGO significantly decreased the frequency of
      GABA-mediated miniature inhibitory postsynaptic currents (mIPSCs) in all nine
      labeled LC neurons. However, DAMGO had no effect on glutamate-mediated miniature
      excitatory postsynaptic currents (mEPSCs) in 12 of 15 neurons. Furthermore, DAMGO
      significantly inhibited the peak amplitude of evoked inhibitory postsynaptic
      currents (eIPSCs) in all 11 labeled neurons, but had no significant effect on the
      evoked excitatory postsynaptic currents (eEPSCs) in 10 of these 11 neurons. Thus,
      data from this study suggest that activation of micro-opioid receptors excites a
      population of spinally projecting LC neurons by preferential inhibition of
      GABAergic synaptic inputs. These findings provide important new information about
      the descending noradrenergic modulation and analgesic mechanisms of opioids.

PMID- 14715152
TI  - Modulation of ATP levels alters the mode of hydrogen peroxide-induced cell death
      in primary cortical cultures: effects of putative neuroprotective agents.
AB  - Oxidative injury is believed to be a major factor in the pathogenesis of a
      variety of neurodegenerative diseases. Additionally, the mode of cell death in
      oxidant-stressed cells can vary. The present study was conducted to evaluate the
      use of a primary neuronal cell-based bioassay in which different modes of oxidant
      induced cell death could be studied and in which putative neuroprotective agents
      could be screened. Addition of 50 microM H(2)O(2) to primary cortical neuronal
      cultures for 1 h under normal ATP conditions resulted in approximately 40% cell
      death, almost exclusively of an apoptotic nature. In this condition, cell death
      was effectively blocked by GM1 ganglioside, the semi-synthetic ganglioside
      derivative LIGA20, the dopamine receptor agonist pramipexole (PPX) and the
      caspase inhibitor Z-VAD-FMK but not by the poly (ADP-ribose) polymerase (PARP)
      inhibitor 3-aminobenzamide (3-AB). Pretreatment of cells with 0.01 microM
      oligomycin for 45 min prior to addition of 50 microM H(2)O(2) caused significant
      ATP depletion and approximately the same amount of cell death as H(2)O(2) alone.
      However, under these conditions, cell death was primarily non-apoptotic in nature
      and GM1, LIGA20 and Z-VAD-FMK had no protective effects. In contrast, AB and PPX
      effectively blocked cell death. These results suggest that cellular ATP plays a
      critical role in determining the mode of cell death in primary neurons and that
      these types of in vitro models may provide a useful system for screening putative
      neuroprotective agents.

PMID- 14715153
TI  - Immunolocalization of estrogen receptor beta in the hypothalamic paraventricular
      nucleus of female mice during pregnancy, lactation and postnatal development.
AB  - Previous studies have shown that estrogen receptor beta (ERbeta) is the
      predominant estrogen receptor in the hypothalamic paraventricular nucleus (PVN)
      of mouse, mediating estrogen regulation of the neuroendocrine activities of the
      PVN, but the exact roles that ERbeta plays in the PVN remain unclear. In this
      study, we used immunocytochemistry to investigate the expression of ERbeta in the
      maternal PVN of mice during pregnancy (pregnant days 8, 10, 12, 15 and 18),
      lactation (postpartum days 1, 4 and 8) as well as in the PVN of the females from
      postnatal days 1, 3, 5, 7, 9, 15, 30 and 70. We found out that ERbeta was
      predominantly localized in the magnocellular divisions of PVN. In the pregnant
      female brain, generally, the ERbeta was lower than that of the postnatal
      development, the lowest level was found at gestational days 10-12; then from
      gestational day 18 to postpartum day 1, it increased to higher levels, followed
      by a decrease from postpartum day 4. During the postnatal development, the
      highest level of ERbeta was found at early postnatal days (before postnatal day
      15), thereafter, it decreased to a lower level. The above results indicate that
      circulating sex steroids may differentially regulate the expression of ERbeta in
      the PVN of mice. It also suggests that this receptor may play important roles in
      the regulation of parturition and in the development, food intake and body weight
      increases of the newborns by acting on the neuropeptides, which were also
      detected in the PVN.

PMID- 14715154
TI  - Peripheral amylin activates circumventricular organs expressing calcitonin
      receptor a/b subtypes and receptor-activity modifying proteins in the rat.
AB  - The pancreatic hormone amylin (AMY) and the AMY-receptor-agonist salmon
      calcitonin (sCT) reduce short-term food-intake after binding to the area postrema
      (AP), a circumventricular organ (CVO) lacking blood-brain-barrier
      characteristics. AMY has also been proposed to induce drinking via another CVO,
      the subfornical organ (SFO). In cellular systems, AMY-binding is generated by
      interaction of calcitonin-receptor a/b (CT((a))/CT((b))) with receptor-activity
      modifying proteins (RAMPs). By using in situ hybridization, the codistribution of
      CT((a))/CT((b)) with RAMP1-3 and c-fos was mapped in CVOs of rats. AMY and sCT
      induced c-fos within the SFO which contained CT((a)) and/or CT((b)) and RAMP1/2
      mRNA. AMY and sCT also activated AP neurons, which express the CT((a)), but not
      the CT((b)), receptor and RAMP2/3 mRNA. These data emphasize the important role
      of these structures as primary targets for circulating AMY.

PMID- 14715155
TI  - Neuronal expression and regulation of CGRP promoter activity following viral gene
      transfer into cultured trigeminal ganglia neurons.
AB  - We have examined the regulation of calcitonin gene-related peptide (CGRP)
      promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral
      vector was used to circumvent the potential complication of examining only a
      small subpopulation of cells in the heterogeneous cultures. Infection with high
      titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter
      linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression
      in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was
      preferentially expressed in neurons, with 91% co-expression with endogenous CGRP.
      In contrast, an adenoviral vector containing a CMV-lacZ reporter was
      predominantly expressed in non-neuronal cells, with only 29% co-expression with
      CGRP. We then asked whether the CGRP promoter in the viral vector could be
      regulated by serotonin receptor type 1 (5-HT(1)) agonists. Promoter activity was
      decreased two- to threefold by treatment with five 5-HT(1B/D) agonists, including
      the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for
      migraine treatment. As controls, CMV promoter activity was not affected, and 5
      HT(1B/D) receptor antagonists blocked the repression caused by sumatriptan and
      eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia
      neurons for studying the mechanisms of triptan drug action on CGRP synthesis.

PMID- 14715156
TI  - Schizophrenia-like behavioral changes after partial hippocampal kindling.
AB  - The effect of hippocampal kindling on behavioral changes following 10 and 21
      hippocampal afterdischarges (ADs) or electrographic seizures was examined in
      behaving rats. As compared to control, non-stimulated rats, 21 but not 10
      hippocampal ADs resulted in a decrease in social contact, an increase in social
      isolation, and an increase in climbing and chasing behavior tested in an open
      field 3 days after cessation of kindling. Porsolt forced swimming test was not
      different among the control, 10- or 21-AD groups of rats. A deficit in
      sensorimotor gating, measured by prepulse inhibition of an acoustic startle, was
      observed in kindled as compared to control rats at 2 weeks after 21 ADs, but not
      after 10 ADs. Similarly, methamphetamine (1 mg/kg i.p.) induced higher locomotor
      activity in kindled rats, as compared to controls, after 21 ADs but not after 10
      ADs. Spontaneous locomotor activity in a novel cage, without drug administration,
      was not different between kindled and control rats. These findings suggest that
      behavioral alterations after repeated hippocampal electrographic seizures may be
      mediated by increased dopaminergic functions, which may also mediate the
      psychiatric symptoms in human epileptic patients.

PMID- 14715157
TI  - Vulnerabilities of ventral mesencephalic neurons projecting to the nucleus
      accumbens following infusions of 6-hydroxydopamine into the medial forebrain
      bundle in the rat.
AB  - The terminal arbors of dopaminergic projections in the nucleus accumbens (Acb)
      core degenerate more rapidly, completely and permanently in a variety of
      neurotoxic circumstances than do those in the medial shell. It is unknown if this
      always reflects purely losses of the distal parts of axons from the core (as
      proposed in methamphetamine intoxication), or whether, in some circumstances, the
      disproportionate loss of core axons may also stem from an intrinsic vulnerability
      to degeneration of core-projecting neuronal perikarya. Experiments described here
      addressed this issue in the following manner. Three days after Fluoro-Gold (FG),
      a retrogradely transported tracer, had been iontophoresed selectively into the
      core or medial shell of male Sprague-Dawley rats, each received an infusion of
      saline vehicle containing or lacking 6-hydroxydopamine (6-OHDA) in the
      ipsilateral medial forebrain bundle (MFB). Twenty-one days later the brains were
      processed to exhibit ventral mesencephalic neurons containing FG. Application of
      an unbiased sampling method revealed substantially greater losses of FG labeled
      neurons relative to controls in rats that had received 6-OHDA lesions and
      deposition of FG in the Acb core as compared to the medial shell. Of the few core
      projecting neurons that remained in the ventral mesencephalon after these
      lesions, 54% did not co-localize tyrosine hydroxylase immunoreactivity (TH-ir)
      and, thus, were not expected to degenerate. The capacity to selectively remove
      core-projecting dopaminergic neurons may be useful in the determination of
      molecular correlates of vulnerability and resistance to neurotoxicity and to
      possibly test the role of the core in reinforcement paradigms.

PMID- 14715158
TI  - Biphasic effects of ethanol on acetylcholine release in the rat prefrontal
      cortex.
AB  - Low doses of ethanol (0.5 g/kg i.p.) increased, while higher doses (1 g/kg i.p.)
      reduced acetylcholine (ACh) release in the rat prefrontal cortex (PFC). Ethanol
      (50-300 mM) applied in the nucleus basalis through a second dialysis probe caused
      concentration-dependent biphasic changes in prefrontocortical ACh release.
      Ethanol apparently acts on cholinergic fibers to modulate ACh transmission in the
      PFC. These results could be of relevance for the bidirectional modulation of
      working memory by ethanol.

PMID- 14715159
TI  - Changes in hippocampal SNAP-25 expression following afferent lesions.
AB  - Reductions in SNAP-25 immunohistochemistry were found after removing the
      glutamatergic and cholinergic inputs to the rat hippocampus. SNAP-25 levels were
      normalised by 1 month after afferent lesions. Surprisingly, a superimposed
      cholinergic lesions did not affect the return to normal SNAP-25 levels after a
      long-term entorhinal cortex lesion. It is concluded that changes in SNAP-25 may
      represent early markers of synaptic loss following afferent lesions to the
      hippocampus.

PMID- 14715162
TI  - Hierarchical combinatorial planning of medical treatment.
AB  - The paper addresses a problem of constructing a composite plan for a medical
      treatment on the basis of hierarchical morphological approach, multicriteria
      ranking, and morphological clique problem. The approach consists of the following
      phases: (a) hierarchical description of the medical plan; (b) generation of local
      alternative actions; (c) multicriteria selection of the local actions; and (d)
      composition of the best local actions into the global composite medical plan. An
      illustrative numerical example for children asthma describes the problem and
      solving processes.

PMID- 14715163
TI  - Application of the Max-Lloyd quantizer for ECG compression in diving mammals.
AB  - This article presents a practical implementation of an ECG compression algorithm
      using a Max-Lloyd quantizer, to optimize the low resources of an ECG acquisition
      and transmission system (telemetry system) for dolphins and human divers. The
      algorithm scheme is based on a first-order differential pulse code modulation
      (DPCM) and uses a Max-Lloyd quantizer to code the difference between the current
      and predicted samples. The use of the non-uniform quantizer instead of a uniform
      quantizer improves the percent root mean-square difference (PRD), thereby
      producing a low distortion in the reconstructed signals. Due to its low
      computational complexity, the compression process can be accomplished on-line
      during the ECG acquisition process.

PMID- 14715164
TI  - Kymograph: a muscle physiology toolkit.
AB  - Kymograph is a freely available, Linux-based data acquisition and control system
      that is designed as a device driver and a series of scriptable tools. It allows
      the creation of scripts for performing a variety of measurements related to
      muscle physiology. It can control hardware (2 analog channels) and capture data
      (up to 16 channels) at rates of up to 1 kHz. It also has the ability to generate
      stimulus control pulses with a resolution of 10 micros. The tools can be used
      with any of the common scripting languages to generate complete control and
      capture routines for performing measurements such as length-tension curves or
      force-velocity relationships. Source code is provided to allow easy extension of
      the software.

PMID- 14715165
TI  - Computerized methods for X-ray-based small bone densitometry.
AB  - Animal models have been widely used to correlate in vivo changes in bone mineral
      density (BMD) with changes in disease state of bone. In small animal models, e.g.
      the hindlimb suspension model of bone loss, a non-invasive assessment of BMD is
      required. X-ray radiography has been surpassed in some cases by quantitative
      computed tomography (QCT) and dual X-ray absorptiometry (DEXA) quantitation.
      However, there are drawbacks in using the computerized methods, especially for
      small animals. In this paper, we present image-processing algorithms to
      quantitatively determine bone area and mineral density in digitized radiographs.
      Image calibration is based on a calibration step wedge, and the algorithm
      automatically detects the steps and computes the calibration data. In addition,
      we demonstrate how the algorithm can accurately determine the cortical outline of
      the bone and provide reliable data and statistics for small animal studies. A
      downloadable implementation example for the popular NIH Image package is
      provided.

PMID- 14715166
TI  - Human-computer interaction in the administration and analysis of
      neuropsychological tests.
AB  - We developed a computerized neuropsychological assessment software, which employs
      innovative features in both the presentation of the tests and the interpretation
      of the subjects' performance. The usability features of the software enabled
      elderly subjects with no computer experience to undergo the cognitive tests,
      without a test administrator being present. New features extracted from reaction
      times allowed for enhancement of the performance analysis of the tests. The
      software was validated using a large group of controls and then administered to a
      group of subjects with age related memory complaints. The results indicate an
      improved sensitivity of two of the computerized tests compared with the mini
      mental state examination, which enabled to separate two groups of subjects from a
      population that was relatively homogenous based on clinical history, neurological
      examination and the mini-mental state examination.

PMID- 14715167
TI  - A graphical tool for parasite genome annotation.
AB  - A graphical tool to facilitate rapid primary annotation of genomic sequence has
      been developed. Within a single interface the user can import sequences or
      database entries, run feature prediction programs and similarity searches, filter
      results, add additional manually found features and notes, and finally export
      annotations for database submission. Integrated rule-based feature corroboration
      and a novel decision support heuristic using ORF orientation, length and base
      composition further enhances the efficiency of the annotation process without
      compromising flexibility. The program has been explicitly tailored to use in
      protozoan parasite genome projects, but can constitute a useful tool for
      prokaryote annotation as well. It is successfully being used by our lab in the
      Trypanosoma cruzi genome project, and can be obtained from the authors upon
      request.

PMID- 14715168
TI  - HeiDATAProVIT-Heidelberg data archiving, tag assembling, processing and
      visualization tool.
AB  - The demands that have to be met by software tools for biomedical data evaluation
      strongly differ depending on the background of their application. In clinical
      routine emphasis is placed on ease of handling and application of standardized
      procedures, whereas in biomedical research the main focus lies on flexibility and
      extensibility. These contradictory requirements are reflected by the design
      principles of existing software solutions: programs for routine application are
      barely extensible or modifiable by the user and the complexity of highly flexible
      data processing tools for research purposes hampers the application of new
      methods to larger data volumes. This gap poses technical difficulties to the
      transfer of methods from research into clinical routine. The software we present
      in this paper bridges this discrepancy by incorporating two different levels of
      application. The lower level offers options to integrate custom written
      MATLAB((R)) processing routines and to add new evaluation schemes to a pool of
      existing procedures. The higher level allows for performing standard evaluations
      by accessing and applying these previously defined procedures. Four basic
      concepts were introduced to ensure that the program is both maximally flexible on
      a lower level and readily applicable on a higher level: the tag concept, the
      concept of modularized visualization, the dummy file concept, and the batchjob
      concept. These concepts are the key to flexibly assemble and apply the three
      universal stages of data evaluation: (1) archiving of acquired data, (2)
      processing the data using signal processing algorithms and (3) visualizing the
      results in appropriate graphical formats. The present paper illustrates the four
      concepts within the two levels of the software architecture. The basic
      functionality and usefulness of the program are demonstrated using an evaluation
      of gait analysis data as sample application. In summary, this software tool
      closely integrates a database for biomedical datasets and an extensible pool of
      evaluation and visualization procedures realized using MATLAB((R)). It is well
      suited both for data processing in clinical routine and for evaluation of
      measurement data in any medical research project.

PMID- 14715169
TI  - In vivo evaluation of a computer planning system for total knee arthroplasty.
AB  - In this paper we report the analysis of a preoperative computer planner for total
      knee arthroplasty (TKA), when applied to a set of patients by different surgeons.
      The goal of this work was to study the repeatability and reliability of computer
      planning, the ergonomy of the system, identify the useful features of this
      technique and the possible drawbacks. The planning system allows the surgeon to
      interactively stimulate the implant on a 3D model of the patient computed from
      computerized tomography (CT) images. In this paper, we summarize the main results
      of a series of evaluation trials carried out by four surgeons on ten patients. We
      measured the variability of the main application parameters, evaluated the
      efficacy and usefulness of the automatic prosthesis positioning provided by the
      system and carefully analyzed the system ergonomy. The system showed satisfactory
      repeatability in the interactive definition of the essential parameters. Moreover
      it showed to be easy to use, consistent, focused on the most important parameters
      and able to improve the surgeon's insight and confidence in the outcome. Further
      steps include clinical studies and direct comparison with standard technique.

PMID- 14715170
TI  - Letter to the editor.

PMID- 14715172
TI  - U.S. healthcare: the intertwined caduceus of physicians, coverage, quality, and
      cost.
AB  - As cardiologists, we should increase our efforts to improve coverage, quality,
      and cost, both by caring for individual patients and by improving our systems.
      How? Coverage: by promoting a coordinated approach, beginning with state
      demonstrations of new safety net and individual and private insurance approaches.
      Quality: by adopting evidence-based practice and adapting practice guidelines for
      payment, beginning with non-payment for class III; by setting standards of
      practice below which we may not fall and paying for quality and service above
      this level; by involving patients as partners in their care and providing them
      with incentives. Cost: by challenging routine practices (why return in one
      year?); by beginning to address the widening gap between what is possible and
      what is affordable, taking part in broader discussions on what is worth the cost,
      supporting tort reform, and proposing alternatives; by improving our systems to
      reduce medical errors and addressing future physician shortages by working in
      teams with primary care physicians and nurses. Let's work with our patients to
      improve their health. Together we can make real progress.

PMID- 14715174
TI  - Optimal glycemic control is associated with a lower rate of target vessel
      revascularization in treated type II diabetic patients undergoing elective
      percutaneous coronary intervention.
AB  - OBJECTIVES: We examined the association between glycemic control determined by
      preprocedural hemoglobin A1c (A1c) and the incidence of target vessel
      revascularization (TVR) in diabetic patients undergoing elective percutaneous
      coronary intervention (PCI). BACKGROUND: Patients with diabetes mellitus (DM)
      have increased rates of restenosis and a worse clinical outcome after PCI than
      patients without DM. METHODS: A total of 239 patients (60 without DM and 179 with
      DM) were enrolled in this study. Optimal glycemic control was defined as A1c < or
      =7%, and suboptimal control was defined as A1c >7%. Follow-up was performed at
      six and 12 months after the index intervention. RESULTS: Diabetic patients with
      optimal glycemic control had a rate of 12-month TVR similar to that of
      nondiabetic patients (15% vs. 18%, p = NS). Diabetic patients with A1c >7% had a
      significantly higher rate of TVR than those with A1c <7% (34% vs. 15%, p = 0.02).
      In a multiple logistic regression analysis, A1c >7% was a significant independent
      predictor of TVR (odds ratio 2.87, 95% confidence interval 1.13 to 7.24; p =
      0.03). Optimal glycemic control was associated with a lower rate of cardiac
      rehospitalization (15% vs. 31%, p = 0.03) and recurrent angina (13% vs. 37%, p =
      0.002) at 12-month follow-up. CONCLUSIONS: In diabetic patients undergoing
      elective PCI, optimal glycemic control (A1c < or =7%) is associated with a lower
      rate of TVR, cardiac rehospitalization, and recurrent angina. These data suggest
      that aggressive treatment of DM to achieve A1c < or =7% is beneficial in
      improving the clinical outcome after PCI.

PMID- 14715175
TI  - Optimization of glycemic control and restenosis prevention in diabetic patients
      undergoing percutaneous coronary interventions.

PMID- 14715176
TI  - Circulating monocytes and in-stent neointima after coronary stent implantation.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      circulating monocytes and in-stent neointimal volume at six-month follow-up.
      BACKGROUND: In-stent neointimal hyperplasia is the main contributing factor to in
      stent restenosis. There is increasing evidence that white blood cells (WBCs),
      especially monocytes, play a central role in restenosis after stent implantation.
      METHODS: We performed coronary stent implantation in 107 patients (107 lesions).
      Peripheral blood was obtained from all patients immediately before coronary
      angiography and every day for seven days after the intervention, and each WBC
      fraction count was analyzed. At scheduled six-month follow-up, all patients
      received angiographic and volumetric intravascular ultrasound analysis. RESULTS:
      The circulating monocyte count increased and reached its peak two days after
      stent implantation (from 350 +/- 167 to 515 +/- 149/mm3, p < 0.01). The maximum
      monocyte count after stent implantation showed a significant positive correlation
      with in-stent neointimal volume at six-month follow-up (r = 0.44, p < 0.0001).
      Other fractions showed neither significant serial changes nor a correlation with
      in-stent neointimal volume. Multiple regression analysis revealed that in-stent
      neointimal volume was independently correlated with stent volume immediately
      after implantation (r = 0.45, p < 0.0001) and maximum monocyte count (r = 0.35, p
      < 0.001). Angiographic restenosis, defined as percent diameter stenosis >50%, was
      observed in 22 patients (21%), and these patients showed a significantly larger
      maximum monocyte count than patients without restenosis (642 +/- 110 vs. 529 +/-
      77/mm3, p < 0.01). CONCLUSIONS: Circulating monocytes increased after coronary
      stent implantation, and the peak monocyte count related to in-stent neointimal
      volume. Our results suggest that circulating monocytes play a role in the process
      of in-stent neointimal hyperplasia.

PMID- 14715177
TI  - The monocyte: the key in the lock to reduce stent hyperplasia?

PMID- 14715178
TI  - Myocardial infarction after percutaneous transluminal septal myocardial ablation
      in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced
      magnetic resonance imaging.
AB  - OBJECTIVES: The aim of this study was to evaluate myocardial infarction induced
      by percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic
      patients with hypertrophic obstructive cardiomyopathy using contrast-enhanced
      (CE) magnetic resonance imaging (MRI). BACKGROUND: Contrast-enhanced MRI
      delineates the extent of myocardial infarction in coronary artery disease, but
      its role in ethanol-induced infarction has not been established. METHODS: Cine
      and CE MRI were performed before and one month after PTSMA in 24 patients. Size
      and location of the induced infarction were related to left ventricular (LV) mass
      reduction, enzyme release, volume of ethanol administered, LV outflow tract
      gradient reduction, and coronary ablation site. RESULTS: One month after PTSMA,
      regional hyperenhancement was visualized in the basal interventricular septum in
      all patients. Mean infarction size was 20 +/- 9 g, corresponding to 10 +/- 5% and
      31 +/- 16% of total LV and septal mass, respectively. Total LV mass decreased
      from 219 +/- 64 to 205 +/- 64 g (p < 0.01), and septal mass from 76 +/- 25 to 68
      +/- 22 g (p < 0.01). Total LV mass reduction exceeded septal mass reduction (p <
      0.01). Infarction size correlated with peak creatine phosphokinase-MB (beta =
      0.67, p < 0.01), volume of ethanol administered (beta = 0.47, p = 0.02), total LV
      and septal mass reduction (beta = 0.50, p = 0.02; beta = 0.73, p < 0.01), and
      gradient reduction (beta = 0.63, p < 0.01). Seven patients with exclusively right
      sided septal infarction had smaller infarction size and less gradient reduction
      than remaining patients with left-sided or transmural infarction (p < 0.01). In
      five of these, PTSMA was performed distal in the target artery. CONCLUSIONS:
      Contrast-enhanced MRI allowed detailed evaluation of size and location of septal
      myocardial infarction induced by PTSMA. Infarction size correlated well with
      clinical indexes of infarct size.

PMID- 14715179
TI  - Early interleukin-1 receptor antagonist elevation in patients with acute
      myocardial infarction.
AB  - OBJECTIVES: We sought to evaluate interleukin-1 receptor antagonist (IL-1Ra)
      levels in patients with ST-segment elevation acute myocardial infarction (AMI)
      upon emergency department (ED) admission in order to assess the sensitivity of
      such a determination by comparison with common markers of myocardial necrosis.
      BACKGROUND: Inflammatory markers are elevated in patients with unstable coronary
      syndromes, but IL-1Ra levels during the early phases of AMI have not been
      previously investigated. METHODS: Levels of IL-1Ra were measured in 44
      consecutive patients with AMI and compared with creatine kinase (CK), CK-MB,
      troponin I, myoglobin, and C-reactive protein (CRP). RESULTS: Upon admission, 82%
      of patients had elevated (>230 pg/ml) IL-1Ra levels, compared with 41% of
      patients with raised CK (p = 0.001), CK-MB (45%, p = 0.002), troponin I (57%, p =
      0.027), myoglobin (48%, p = 0.004), and CRP (57%, p = 0.019) levels. The IL-1Ra
      values were significantly higher in patients with heralded AMI than in those
      without pre-infarction angina (671 vs. 320 pg/ml, p = 0.013). The sensitivity of
      IL-1Ra determination increased to 86% when chest pain duration was < or =3 h and
      to 91% if heralded infarction occurred. CONCLUSIONS: Our study indicates that,
      unlike markers of necrosis, an increase of IL-1Ra levels occurs early in patients
      with AMI, is more significant in those with heralded infarction and symptom onset
      < or =3 h, and precedes the release of markers of necrosis. Thus, IL-1Ra
      determination may be an important early adjuvant toward the diagnosis of AMI in
      the ED.

PMID- 14715180
TI  - Azimilide decreases recurrent ventricular tachyarrhythmias in patients with
      implantable cardioverter defibrillators.
AB  - OBJECTIVES: This study evaluated the effects of azimilide dihydrochloride (AZ) on
      anti-tachycardia pacing (ATP) and shock-terminated events in patients with
      implantable cardioverter defibrillators (ICDs). BACKGROUND: Animal studies have
      shown the effectiveness of AZ for therapy of supraventricular and ventricular
      tachycardia (VT). Azimilide dihydrochloride was investigated as adjunctive
      treatment for reducing the frequency of VT and, thus, the need for ICD therapies,
      including ATP and cardioversion/defibrillation (ICD shocks) in patients with
      inducible monomorphic VT. METHODS: A total of 172 patients were randomized to
      daily treatment with placebo, 35 mg, 75 mg, or 125 mg of oral AZ in this dose
      ranging pilot study of patients with ICDs. The majority of patients had a history
      of documented remote myocardial infarction and congestive heart failure New York
      Heart Association class II or III. RESULTS: The frequency of appropriate shocks
      and ATP were significantly decreased among AZ-treated patients compared with
      placebo patients. The incidence of ICD therapies per patient-year among the
      placebo group was 36, and it was 10, 12, and 9 among 35 mg, 75 mg, and 125 mg AZ
      patients, respectively (hazard ratio = 0.31, p = 0.0001). Azimilide
      dihydrochloride was generally well tolerated and did not affect left ventricular
      ejection fraction or minimal energy requirements for defibrillation or pacing.
      CONCLUSIONS: Azimilide dihydrochloride may be a safe and effective drug for
      reducing the frequency of VT and ventricular fibrillation in patients with
      implanted ICDs.

PMID- 14715181
TI  - Filling the need for new antiarrhythmic drugs to prevent shocks from implantable
      cardioverter defibrillators.

PMID- 14715182
TI  - Long-term risk of recurrent atrial fibrillation as documented by an implantable
      monitoring device: implications for optimal patient care.
AB  - OBJECTIVES: The present study determined the incidence and time course of atrial
      fibrillation (AF) recurrences in patients with a history of AF and fitted with an
      implantable monitoring device. BACKGROUND: The long-term risk of undetected
      recurrence of AF in patients receiving stable antiarrhythmic therapy remains
      uncertain. METHODS: In 110 patients with a class I indication for physiologic
      pacing and a history of AF, a pacemaker with dedicated functions for AF detection
      and electrogram storage was implanted, and antiarrhythmic drug treatment was
      optimized. Patients were regularly followed up with evaluation of AF-related
      symptoms, a resting electrocardiogram (ECG), and interrogation of device memory.
      The incidence of AF recurrences lasting >48 h in asymptomatic patients presenting
      in sinus rhythm (SR) at the respective follow-up visit constituted the primary
      end point of this prospective study. RESULTS: During 19 +/- 11 months, 678 follow
      up visits were performed. Atrial fibrillation was documented in 51 patients (46%)
      by ECG recording and in 97 patients (88%) by a review of stored electrograms (p <
      0.0001). Device interrogation revealed AF recurrences lasting >48 h in 50
      patients, 19 of whom (38%) were completely asymptomatic and in SR at subsequent
      follow-up. In 11 (16%) of 67 patients with device-confirmed freedom from AF for >
      or =3 months, AF lasting >48 h recurred subsequently. CONCLUSIONS: This
      prospective study demonstrates a high incidence of recurrent AF despite optimized
      antiarrhythmic therapy. Of particular note, AF relapses >48 h remained totally
      asymptomatic in a significant proportion of patients. Freedom from AF for > or =3
      months did not preclude subsequent long-lasting AF recurrence.

PMID- 14715183
TI  - The impact of asymptomatic atrial fibrillation.

PMID- 14715184
TI  - Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart
      failure independent of ventricular hypertrophy.
AB  - OBJECTIVES: We tested a hypothesis that elevation of the plasma level of brain
      natriuretic peptide (BNP) is one of the characteristics of patients with
      diastolic heart failure (DHF) independent of left ventricular (LV) hypertrophy.
      BACKGROUND: The clinical characteristics of DHF are not well acknowledged,
      although DHF has become a great social burden. Such a lack of clinical
      information leads to inaccuracy in the diagnosis of DHF. We have demonstrated
      enhancement of ventricular production of BNP with progression of maladaptive
      ventricular hypertrophy, but not with development of compensatory hypertrophy in
      an animal DHF model. METHODS: Of 372 patients who presented to the emergency
      department because of acute pulmonary congestion without acute coronary syndrome
      between January 1996 and May 2002, those with an ejection fraction > or =45% upon
      admission, who were stably controlled at least for a year in our outpatient
      clinics, comprised the DHF group (n = 19). A control group consisted of 22
      hypertensive patients with a LV mass index greater than or equal to its minimum
      value of the DHF group and an ejection fraction > or =45%, in whom cardiac
      symptoms had not occurred. RESULTS: Despite a similar distribution of LV mass
      index, the BNP level was higher in the DHF group than in the control group (149
      +/- 38 vs. 31 +/- 5 pg/ml, p < 0.01). There was no difference in LV cavity size
      or parameters derived from pulsed Doppler transmitral flow velocity curves.
      CONCLUSIONS: An elevation of BNP may be a hallmark of patients with or at risk of
      DHF among subjects with preserved systolic function independent of LV
      hypertrophy.

PMID- 14715185
TI  - Incidence, predictors at admission, and impact of worsening renal function among
      patients hospitalized with heart failure.
AB  - OBJECTIVES: The goal of this study was to determine the prevalence of worsening
      renal function (WRF) among hospitalized heart failure (HF) patients, clinical
      predictors of WRF, and hospital outcomes associated with WRF. BACKGROUND:
      Impaired renal function is associated with poor outcomes among chronic HF
      patients. METHODS: Chart reviews were performed on 1,004 consecutive patients
      admitted for a primary diagnosis of HF from 11 geographically diverse hospitals.
      Cox regression model analysis was used to identify independent predictors for
      WRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 micromol/l).
      Bivariate analysis was used to determine associations of development of WRF with
      outcomes (in-hospital death, in-hospital complications, and length of stay).
      RESULTS: Among 1,004 HF patients studied, WRF developed in 27%. In the majority
      of cases, WRF occurred within three days of admission. History of HF or diabetes
      mellitus, admission creatinine > or =1.5 mg/dl (132.6 micromol/l), and systolic
      blood pressure >160 mm Hg were independently associated with higher risk of WRF.
      A point score based on these characteristics and their relative risk ratios
      predicted those at risk for WRF. Hospital deaths (adjusted risk ratio [ARR] 7.5;
      95% confidence intervals [CI] 2.9, 19.3), complications (ARR 2.1; CI 1.5, 3.0),
      and length of hospitalizations >10 days (ARR 3.2, CI 2.2, 4.9) were greater among
      patients with WRF. CONCLUSIONS: Worsening renal function occurs frequently among
      hospitalized HF patients and is associated with significantly worse outcomes.
      Clinical characteristics available at hospital admission can be used to identify
      patients at increased risk for developing WRF.

PMID- 14715186
TI  - The cardiac atria are chambers of active remodeling and dynamic collagen turnover
      during evolving heart failure.
AB  - OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in
      atrial chamber remodeling was studied in a canine model of heart failure (HF).
      BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF.
      Studies of the structural mechanisms of cardiac remodeling have been limited to
      the left ventricle. The structural alterations associated with atrial chamber
      remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched
      dogs were subjected to right ventricular pacing (240 beats/min) for one and three
      weeks to produce early and severe HF, respectively. Atrial tissues were assessed
      for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures
      were significantly increased in early and severe HF. The LA wall tension index
      was significantly increased at both HF stages by 116% and 443%, respectively.
      Atrial collagen synthesis and degradation were significantly increased in severe
      HF. Gelatinase activity was significantly increased at both early and severe
      stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)
      9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was
      significantly correlated with gelatinase activity and collagen synthesis.
      Although total atrial collagen content was not changed, disarray of collagen
      fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was
      also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling
      in canine pacing-induced HF, which is characterized by myocyte hypertrophy and
      dynamic collagen turnover. Atrial remodeling may contribute to the development of
      atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic
      target.

PMID- 14715187
TI  - Transesophageal echocardiography improves risk assessment of thrombolysis of
      prosthetic valve thrombosis: results of the international PRO-TEE registry.
AB  - OBJECTIVES: The goal of this study was to evaluate whether quantitation of
      thrombus burden with transesophageal echocardiography (TEE) can help risk
      stratify patients undergoing thrombolysis of prosthetic valve thrombosis (PVT).
      BACKGROUND: Thrombolytic therapy of PVT has an unpredictable risk of embolization
      and complications. METHODS: An international registry of patients with suspected
      PVT undergoing two-dimensional/Doppler and TEE before thrombolysis was
      established. All TEE studies were reviewed and quantitated by a single observer
      blinded to all data. RESULTS: From 1985 to 2001, 107 patients (71 females; age 24
      to 86 years) from 14 centers (6 in the U.S.) were identified. The majority of
      cases involved the mitral valve (79 mitral, 13 aortic, and 15 tricuspid).
      Hemodynamic success rate was achieved in 85% and was similar across valves.
      Overall complications were observed in 17.8%, and death in 5.6%. Predictors of
      complications were: New York Heart Association (NYHA) functional class, presence
      of shock, sinus tachycardia, hypotension, previous history of stroke, thrombus
      extension beyond the valve ring, and thrombus area. Multivariate analysis
      demonstrated that two variables were independent predictors of complications:
      thrombus area by TEE (odds ratio [OR] 2.41 per 1 cm2 increment, 95% confidence
      interval [CI] 1.12 to 5.19) and prior history of stroke (OR 4.55, 95% CI 1.35 to
      15.38). A thrombus area <0.8 cm2 identified patients at lower risk for
      complications from thrombolysis, irrespective of NYHA functional class.
      CONCLUSIONS: In PVT, the thrombus size imaged with TEE is a significant
      independent predictor of outcome. Transesophageal echocardiography can identify
      low-risk groups for thrombolysis irrespective of symptom severity and is
      therefore recommended in the management of prosthetic valve thrombosis.

PMID- 14715188
TI  - Tissue doppler imaging predicts recovery of left ventricular function after
      recanalization of an occluded coronary artery.
AB  - OBJECTIVES: We tested the hypothesis that the tissue Doppler imaging (TDI)
      derived positive preejection velocity (+VIC) can predict the recovery of
      contractile function after revascularization in patients with a recent myocardial
      infarction. BACKGROUND: In experimental studies, the presence and extent of TDI
      derived +VIC correlated with the extent of viable myocardium. METHODS: Forty
      three patients with a large myocardial infarction and an occluded left anterior
      descending (n = 38) or dominant right coronary (n = 5) artery were selected. The
      median duration of occlusion was 24 h. Longitudinal myocardial velocities were
      recorded at rest by pulsed-wave TDI echocardiography 6 +/- 2 h after
      revascularization. Functional recovery was defined as an increase in segmental
      chordal shortening > or =10% at three-month follow-up left ventricular angiogram
      as compared with baseline. RESULTS: A good quality TDI signal was obtained in 309
      of 324 analyzed segments (95.4%). Severe dysfunction was present in 198 segments
      of which 126 (64%) showed recovery at three-month follow-up. Sampling of all
      dysfunctional segments lasted 11 +/- 4 min per patient. Sensitivity, specificity,
      and accuracy of the +VIC to predict segmental recovery were 91%, 71%, and 84%,
      respectively. The percentage of segments that were dysfunctional at angiography
      but showed a +VIC correlated with improvement of both global left ventricular
      ejection fraction (r = 0.60, p = 0.001) and wall motion score index (r = -0.78, p
      < 0.0001) at follow-up. CONCLUSIONS: Assessment of +VIC by pulsed-wave TDI is a
      simple and accurate method that predicts recovery of contractile function after
      revascularization in patients with a recent myocardial infarction.

PMID- 14715189
TI  - Mechanism(s) of selective systolic blood pressure reduction after a low-dose
      combination of perindopril/indapamide in hypertensive subjects: comparison with
      atenolol.
AB  - OBJECTIVES: The goal of this study was to determine if a low-dose combination of
      the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic
      indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as
      brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to
      determine the hemodynamic factors influencing independently brachial and central
      SBP: pulse wave velocity (PWV) and pattern of wave reflections. BACKGROUND: In
      high cardiovascular risk populations, angiotensin blockade improves survival
      without affecting brachial SBP and diastolic blood pressure (DBP). Whether
      central SBP, which is physiologically lower than brachial SBP, is significantly
      reduced has never been investigated. METHODS: This study was a double-blind
      randomized trial for one year in patients with essential hypertension. RESULTS:
      For a similar DBP reduction, Per/Ind decreased SBP significantly more than
      atenolol, with a more pronounced reduction for central than for brachial SBP.
      After one year, the difference between brachial and central SBP was maintained by
      Per/Ind (8.28 +/- 1.53 mm Hg) and significantly attenuated by atenolol (0.29 +/-
      1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was
      mean blood pressure. Under Per/Ind, this parameter played a minor role, and the
      central SBP reduction implied a major role for disturbed PWV and wave
      reflections. CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of
      brachial SBP is achieved with a significantly greater reduction of central SBP.
      This hemodynamic profile reflects changes of wave reflections issued from distal
      arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to
      improve vessel wall structure.

PMID- 14715190
TI  - Systemic ventricular function in patients with transposition of the great
      arteries after atrial repair: a tissue Doppler and conductance catheter study.
AB  - OBJECTIVES: The aim of this study was to assess the utility of tissue Doppler
      echocardiography in the setting of repaired transposition of the great arteries
      when the right ventricle (RV) functions as the systemic ventricle. BACKGROUND:
      Myocardial acceleration during isovolumic contraction, "isovolumic myocardial
      acceleration" (IVA), has been validated as a sensitive non-invasive method of
      assessing RV contractility. Although traditional indexes may be less valid for
      the abnormal RV, the relative insensitivity of IVA to an abnormal load makes it a
      potentially powerful clinical tool for the assessment of RV disease. METHODS: We
      examined 55 controls and 80 patients (mean age 22 years) with transposition, who
      had undergone atrial repair at age 8 (0.3 to 72) months. A subgroup of 12
      underwent cardiac catheterization. The RV systolic function was derived by
      analysis of pressure-volume relationships and IVA both at rest and during
      dobutamine stress. In all 80, myocardial velocities were sampled in the RV free
      wall. RESULTS: During dobutamine (10 microg/kg/min for 10 min), the increase of
      IVA mirrored the increase in end-systolic elastance (r = 0.69, p < 0.02). In the
      group as a whole, IVA was reduced compared with the subpulmonary RV and the
      systemic left ventricle of controls. There was abnormal wall motion in 44
      patients, which was associated with reduced IVA. Diastolic myocardial velocities
      were also abnormal but unrelated to the presence of wall motion abnormalities.
      CONCLUSIONS: The IVA can accurately assess changes in RV contractile function in
      patients with an RV as the systemic ventricle. Global long-axis RV function is
      reduced in patients with transposition, and this is associated with abnormal
      regional function.

PMID- 14715191
TI  - Stenting the neonatal arterial duct in duct-dependent pulmonary circulation: new
      techniques, better results.
AB  - OBJECTIVES: The goal of this study was to assess a new approach to stent the
      arterial duct in neonates with a duct-dependent pulmonary circulation.
      BACKGROUND: Previous attempts to stent the neonatal arterial duct were
      unsatisfactory. Learning from these failures, we speculated that covering the
      complete length of the duct with current low-profile stents might avoid previous
      problems. METHODS: Ten neonates with duct-dependent pulmonary circulations
      through a short straight duct were treated with stent implantation. The duct was
      crossed with an atraumatic 0.014-inch wire. A low-profile premounted coronary
      stent (outer diameter <4F, length 13 to 24 mm, diameter 3.0 to 4.0 mm) was
      positioned within the duct, not protected by a sheath; care was taken to cover
      the complete length of the duct from the aortaductal junction until well within
      the pulmonary trunk. RESULTS: All stents could safely be deployed with adequate
      pulmonary flow at early- and medium-term follow-up. There were no procedure
      related complications; one patient died early from sepsis. All patients had
      adequate relief of cyanosis for at least three to four months. During follow-up,
      the pulmonary vasculature bed had grown without distortion. Acute occlusion of a
      stented duct was not observed. Ductal flow progressively decreased slowly over
      several months by luminal narrowing, until the stented duct had either become
      redundant or was dilated/restented or until elective staged surgery was
      performed. CONCLUSIONS: With current technology, complete stenting of a short
      straight duct is a safe and effective palliation, allowing adequate growth of the
      pulmonary arteries.

PMID- 14715192
TI  - Outcome of patients with double-inlet left ventricle or tricuspid atresia with
      transposed great arteries.
AB  - OBJECTIVES: We sought to determine the long-term outcomes and risk factors for
      mortality in patients with double-inlet left ventricle (DILV) or tricuspid
      atresia with transposed great arteries (TA-TGA). BACKGROUND: Patients with DILV
      or TA-TGA are at risk of systemic outflow obstruction and a poor outcome. The
      impact of various management strategies on the long-term outcomes of these
      patients remains unknown. METHODS: We reviewed the outcomes of 164 consecutive
      pediatric patients with DILV or TA-TGA who underwent surgical palliation between
      1983 and 2002. Patients with a Holmes heart or heterotaxy syndrome or who were
      lost to follow-up (n = 24) were excluded. Risk factors for mortality or the need
      for orthotopic heart transplantation (OHT) were assessed by multivariate
      analysis. RESULTS: There were 105 patients with DILV and 35 patients with TA-TGA.
      The overall mortality rate, including OHT, was 29%. Patients with DILV had a
      lower mortality rate than patients with TA-TGA (23% vs. 49%, p = 0.007).
      Multivariate analysis showed the presence of arrhythmia and pacemaker requirement
      as independent risk factors for mortality, whereas pulmonary atresia or stenosis
      and pulmonary artery banding were associated with decreased mortality. Gender,
      era of birth, aortic arch anomaly, and systemic outflow obstruction were not risk
      factors. The perioperative and overall mortality were similar between patients
      who underwent the Damus-Kaye-Stansel procedure beyond the neonatal period and
      those had subaortic resection. CONCLUSIONS: The mortality of patients with DILV
      or TA-TGA remains high. The outcomes of these patients are influenced by
      restriction of pulmonary blood flow, arrhythmia, and pacemaker requirement.
      Surgical palliation to relieve systemic outflow obstruction is not associated
      with a poor outcome.

PMID- 14715193
TI  - Novel and traditional cardiovascular risk factors in children after Kawasaki
      disease: implications for premature atherosclerosis.
AB  - OBJECTIVES: We determined the profile of cardiovascular risk factors in children
      late after Kawasaki disease (KD) and compared it with that of age-matched healthy
      children. BACKGROUND: Concerns have been raised regarding the possibility of a
      predisposition of KD to premature atherosclerosis later in life. METHODS: A
      cohort of 102 subjects were studied: 37 KD patients with coronary aneurysms
      (group I), 29 KD patients with normal coronary arteries (group II), and 36
      healthy age-matched children (group III). The fasting total cholesterol, high
      density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol,
      apolipoprotein (apo) A-I, apoB, and homocysteine levels were compared among the
      three groups. In addition, blood pressure and brachioradial arterial stiffness,
      as determined by pulse wave velocity (PWV), were measured and compared. RESULTS:
      Group I subjects had lower HDL cholesterol (p = 0.016) and apoA-I levels (p =
      0.044) and higher apoB levels (p = 0.029) and PWV (p = 0.001) than group III
      control subjects. Likewise, the apoB levels (p = 0.007) and PWV (p = 0.042) were
      higher in group II than in III subjects, although their HDL cholesterol (p =
      0.54) and apoA-I (p = 0.52) levels were similar. The LDL cholesterol levels were
      higher in group I and II patients than in controls, although not statistically
      significant (p = 0.17). Blood pressure and homocysteine levels did not differ
      among the groups. CONCLUSIONS: An adverse cardiovascular risk profile, as
      characterized by a proatherogenic alteration of the lipid profile and increased
      arterial stiffness, occurs in children after KD. The profile is worse in those
      with than in those without coronary aneurysms.

PMID- 14715194
TI  - Angiotensin receptor blockade improves myocardial beta-adrenergic receptor
      signaling in postinfarction left ventricular remodeling: a possible link between
      beta-adrenergic receptor kinase-1 and protein kinase C epsilon isoform.
AB  - OBJECTIVES: We tested the hypothesis that angiotensin II type 1 receptor blocker
      (ARB) may improve beta-adrenergic receptor (AR) coupling in heart failure (HF)
      after myocardial infarction (MI). BACKGROUND: Beta-AR desensitization is one of
      the mechanisms underlying the transition from compensated to decompensated HF.
      Beta-adrenergic receptor kinase-1 (ARK1), which can be induced by protein kinase
      C (PKC) in vitro, is activated in the failing myocardium, resulting in beta-AR
      uncoupling. METHODS: Models of MI in rats were produced by ligation of left
      coronary artery. Four weeks after surgery, they were randomized to vehicle
      (MI/control [C]) or candesartan (10 mg/kg/day) treatment (MI/ARB). Sham-operated
      rats, or shams, served as controls. RESULTS: After two weeks of treatment,
      echocardiography and hemodynamics showed that the left ventricular (LV) dimension
      increased and that the percent of fractional shortening and maximum rate of rise
      in left ventricular pressure (dP/dt) decreased in MI rats compared with shams.
      There were no differences in these indexes between MI/C and MI/ARB. An increase
      in maximum dP/dt under isoproterenol (ISO) stimulation was attenuated in MI/C but
      improved in MI/ARB. Reductions in the percentage of high-affinity sites of beta
      AR and ISO-stimulated cyclic adenosine monophosphate production in noninfarcted
      myocardium were also improved by ARB treatment. Up-regulation of beta-ARK1 and
      PKC-epsilon isoform protein levels and activation of PKC in noninfarcted
      myocardium from MI/C were both inhibited by ARB treatment. CONCLUSIONS: Treatment
      with ARB during the chronic phase of MI improved beta-AR coupling in noninfarcted
      myocardium without affecting basal LV function. Cross-talk between beta-AR and
      angiotensin signaling through beta-ARK1 and PKC-epsilon may be responsible for
      the phenomenon.

PMID- 14715195
TI  - Severe ostial saphenous vein graft disease leading to acute coronary syndromes
      following proximal aorto-saphenous anastomoses with the symmetry bypass connector
      device: is it a suture device or a "stent"?
AB  - The Symmetry Bypass Connector (St. Jude Medical, St. Paul, Minnesota) is a
      nitinol, star-shaped device that was designed to facilitate placement of
      sutureless aorto-saphenous anastomoses during off-pump coronary artery bypass
      graft surgery (CABG). Although the device is approved for clinical use in Europe
      and the U.S., its short- and long-term safety and efficacy are not established.
      We report on 5 of 121 patients undergoing CABG who presented with an acute
      coronary syndrome two to five months following placement of this device. In each
      patient, all saphenous vein grafts (SVGs) placed (n = 11) with the device were
      totally occluded (n = 6) or compromised by ostial stenoses (n = 5). Treatment
      consisted of repeat CABG in one patient and percutaneous coronary intervention
      (PCI) in four patients with cutting balloon atherotomy and stenting. Following
      PCI, two of four patients presented again within two months with near-occlusive
      ostial restenosis in all stents placed. Intracoronary ultrasound showed severe
      neointimal hyperplasia, but only at the proximal interface of the device and
      stent. One patient was treated with brachytherapy in two SVGs but had a
      recurrence four months later and was treated with drug-eluting stents in both
      restenotic segments. Recalcitrant neointimal hyperplasia is postulated to be
      involved in the pathogenesis of anastomotic device stenosis, possibly similar to
      in-stent restenosis. Prospective randomized clinical trials are needed to assess
      the clinical safety and efficacy of this device. Pending such studies,
      consideration should be given in limiting its use to cases of unacceptably high
      risk of stroke during aortic cross-clamping. Dual antiplatelet agents, evaluation
      for ischemia, and close follow-up are warranted in patients that have already
      received the device.

PMID- 14715196
TI  - The year in echocardiography.

PMID- 14715197
TI  - Drug reimportation: sitting in the middle.

PMID- 14715198
TI  - Hemodynamic profiles in heart failure patients.

PMID- 14715200
TI  - Matrix metalloproteinases in atrial fibrillation.

PMID- 14715203
TI  - Trends in utilization of antithrombotic therapy in patients with atrial
      fibrillation before stroke onset in a community-based study, from 1985 through
      1997. From scientific evidence to practice.
AB  - BACKGROUND: Despite the significant beneficial effects of antithrombotic therapy
      in primary prevention of stroke in patients with chronic nonvalvular atrial
      arrhythmia, this prevention therapy is underutilized. We conducted this
      population-based study to determine the rates and the trends of utilization of
      antithrombotic therapy for stroke patients with atrial fibrillation before stroke
      onset, and to evaluate indirectly the impact of medical recommendations on
      physician practice. Our aim was not to evaluate the efficacy of such prevention
      therapy. METHODS: From 2,330 men and women of any age registered for a first-ever
      stroke from 1985 to 1997 in a community-based study, we selected 599 patients
      admitted for ischemic stroke or TIA, associated with prior atrial fibrillation.
      Previous antithrombotic treatment before stroke onset was recorded and we
      evaluated the ratio of stroke patients who had received antithrombotic treatment
      for atrial fibrillation, from 1985 through 1997. RESULTS: Our study was performed
      to evaluate the practice of physicians in the prevention of stroke, and not to
      evaluate the efficacy of the anticoagulants in the prevention of stroke. Atrial
      fibrillation before stroke onset was identified in 599 patients. Of these, 222
      (37%) received no antithrombotic therapy, 65 (10.8%) received an anticoagulant
      alone, 147 (24.5%) received an antiplatelet agent alone and 10 (1.7%) received
      both anticoagulation and antiplatelet treatment. From 1985 to 1988, the
      proportion of treated atrial fibrillation before stroke was small (14.6%). This
      increased to 21.5% within the period 1989-1991, to 40.3% within the period 1992
      1994 and then to 47.6% within the period 1995-1997. It appears that the most
      significant change occurred within the period 1992-1994 (14.6% of treated atrial
      fibrillation within the period 1985-1987 constituted to 40.3% within the period
      1992-1994) (P < 0.05), with a current rate of utilization of antithrombotic
      therapy close to 50%. The logistic regression analysis concerning anticoagulant
      therapy before stroke onset as a dependent variable, found that the factors
      independently associated with the use of anticoagulants before stroke were the
      lack of arterial hypertension and a history of smoking. The factors independently
      associated with the use of aspirin before stroke were arterial hypertension and
      lower limb peripheral vascular disease. CONCLUSION: For primary prevention of
      stroke onset in patients with atrial fibrillation, therapeutic trials have
      changed medical practices although not to ideal levels because close to 50% of
      patients with atrial fibrillation experiencing an acute stroke or TIA received
      antithrombotic treatment. Therefore, clinical practice is inconsistent with the
      guidelines resulting from therapeutic trials. It is necessary to know the reasons
      for this inconsistency and to improve medical information about the
      cerebrovascular risk of atrial fibrillation and the efficacy of anticoagulants in
      stroke prevention in this condition.

PMID- 14715204
TI  - Quality of care in stroke prevention: results of an audit study among general
      practitioners.
AB  - BACKGROUND: In identifying opportunities to improve the quality of stroke
      prevention in general practice, insight in areas of suboptimal care is essential.
      This study investigated the quality of care in stroke prevention in general
      practice and its relation to the occurrence of stroke. METHODS: Retrospective
      case-based audit with guideline-based review criteria and final judgment of
      suboptimal care by an expert panel. RESULTS: A total of 292 stroke patients were
      identified through stroke registers of two main referral hospitals for stroke in
      Rotterdam. The general practitioners (GPs) (n = 95) of these patients were
      approached. The overall response rate from GPs was 81%, and a total of 193
      patients from 77 GPs were included in the study. Data on the process of care at
      patient level were collected by chart review and by structured interviews with
      GPs during site visits. All cases were presented to a six-member panel of GPs and
      neurologists. In 44% of the cases, suboptimal care was identified (31% judged as
      possibly or likely failing to prevent stroke). Of the total number of identified
      shortcomings, 52% was related to inadequate hypertension control, particularly
      lack of follow-up after established hypertension. Another 17% of identified
      shortcomings concerned inadequate cardiovascular risk assessment. CONCLUSIONS: A
      substantial number of shortcomings in care, particularly in the domain of
      hypertension control and the assessment of patient's risk profiles for
      cardiovascular disease (CVD), were identified. This study suggests that improving
      preventive care delivery in general practice could reduce the occurrence of
      stroke.

PMID- 14715205
TI  - Effects of the Quebec Heart Health Demonstration Project on adult dietary
      behaviours.
AB  - BACKGROUND: There are few studies which have evaluated the dietary impact of
      multiple community-based cardiovascular disease prevention programs. METHODS: A 5
      year, multifactorial community-based heart disease prevention program was
      conducted by regional public health departments in three sites: urban, suburban
      and rural. The experimental and control communities were composed of independent
      samples of 4,863 adults in 1993 and 5,260 in 1997. The impact of the program on
      diet was assessed by a validated, self-administered food frequency questionnaire
      which yielded a Global Dietary Index (GDI). RESULTS: The urban and suburban sites
      showed improvements in mean GDI in both exposed and non-exposed groups while the
      rural site mean GDI showed deterioration in both groups (n.s.). The analysis of
      variance showed that the group x year interaction terms were not significant for
      each site and sex, indicating that the intervention did not have measurable
      effects on dietary behaviours. Inclusion of confounding variables did not alter
      those findings. Analyses of specific food group indices gave similar results.
      CONCLUSIONS: Future intervention programs could benefit from considering physical
      and social environments as well as public policy changes to improve efficacy.

PMID- 14715206
TI  - Practical markers of the transition from aerobic to anaerobic metabolism during
      exercise: rationale and a case for affect-based exercise prescription.
AB  - BACKGROUND: The high rates of dropout from exercise programs may be attributed in
      part to the poor ability of most individuals to accurately self-monitor and self
      regulate their exercise intensity. The point of transition from aerobic to
      anaerobic metabolism may be an appropriate level of exercise training intensity
      as it appears to be effective and safe for a variety of populations. Possible
      practical markers of this event were compared. METHODS: Two samples of 30 young
      and healthy volunteers each participated in incremental treadmill tests until
      volitional exhaustion. The ventilatory threshold, a noninvasive estimate of the
      aerobic-anaerobic transition, was identified from gas exchange data. Heart rate,
      self-ratings of affective valence (pleasure-displeasure), perceived activation,
      and perceived exertion were recorded every minute. RESULTS: In both samples,
      heart rate, perceived activation, and perceived exertion rose continuously,
      whereas the ratings of affective valence showed a pattern of quadratic decline,
      initiated once the ventilatory threshold was exceeded. CONCLUSIONS: Exercise
      intensity that exceeds the point of transition from aerobic to anaerobic
      metabolism is accompanied by a quadratic decline in affective valence. This
      marker may be useful in aiding exercisers to recognize the transition to
      anaerobic metabolism and, thus, more effectively self-monitor and self-regulate
      the intensity of their efforts.

PMID- 14715207
TI  - A cross-national comparison of lifestyle between China and the United States,
      using a comprehensive cross-national measurement tool of the healthfulness of
      lifestyles: the Lifestyle Index.
AB  - BACKGROUND: Extensive studies have revealed the importance of a healthy lifestyle
      and the role of each lifestyle factor in health. However, lifestyle factors have
      rarely been studied simultaneously. The authors propose an integrated approach to
      summarize total healthfulness of lifestyles and to enhance understanding of
      lifestyle patterns across countries. METHODS: The authors created an overall
      measure of lifestyle called the Lifestyle Index (LI), integrating diet, physical
      activity, smoking, and alcohol use to provide a global tool of monitoring
      healthfulness and patterns of lifestyles. Using the LI, the authors conducted a
      cross-national comparison between China (n = 8352) and the United States (n =
      9750). RESULTS: The LI effectively reflected the healthfulness of lifestyle
      components in both countries. The mean of the LI scores was slightly higher in
      China than the US. Scores of diet quality, physical activity, and smoking were
      higher in China, but scores of alcohol behavior were higher in the US. Similar
      lifestyle patterns but different unhealthy behaviors were identified in these
      countries. CONCLUSIONS: An assessment of total healthfulness of lifestyles and a
      better understanding of lifestyle patterns across countries using the LI can
      provide practical guidance to developing and targeting public health promotion
      activities to improve global public health.

PMID- 14715208
TI  - Prevention of mildly overweight children from development of more overweight
      condition.
AB  - BACKGROUND: A follow-up study has reported that not only highly obese but also
      mildly obese children are becoming heavier during the elementary school children.
      Then we determined the effect of programs for the screening and treatment of
      overweight elementary school children whether the programs prevented mildly
      overweight children from development of more overweight condition. METHODS:
      Subjects were 40 overweight children who participated in both screening and
      treatment programs. As controls, only 240 children who participated in the
      screening program were used. The mean observation periods of the subjects and
      controls were 14 and 12 months, respectively. RESULTS: In both groups, older and
      heavier children significantly decreased their indices of overweight (percent
      relative body weight; %RBW), indicating that mildly obese children worsened their
      %RBW. However, the incidence of children who worsened their %RBW was
      significantly lower in the subjects (5 of 40) than in the controls (133 of 240)
      (P < 0.0001). Finally, the subjects significantly reduced their mean %RBW (P <
      0.0001) and the controls significantly worsened it (P = 0.0093). CONCLUSION: The
      treatment program was found important because it prevents mildly overweight
      children who may worsen their overweight indices without the program from
      developing more overweight condition.

PMID- 14715209
TI  - Self-reported overweight and obesity are not associated with concern about enough
      food among adults in New York and Louisiana.
AB  - BACKGROUND: A causal relationship between hunger and obesity has been postulated.
      Two cross-sectional studies have found evidence to suggest an association between
      obesity and food insecurity among adult women, and a third study suggests an
      association between underweight and food insecurity among men. The purpose of
      this study was to investigate the association between concern about enough food
      and obesity in an adult population at the state level. METHODS: A cross-sectional
      analysis was conducted using 1999 data from the Behavioral Risk Factor
      Surveillance System (BRFSS), Social Context Module (n = 3,945). RESULTS: An 8.0%
      prevalence of concern about enough food was found in Louisiana, and an 11.8%
      prevalence was found in New York, and was positively associated with morbid
      obesity, RR = 2.20 (95% CI = 1.24, 3.90) and RR = 2.23 (95% CI = 1.30, 3.84),
      respectively. However, this association became nonsignificant after controlling
      for education, income, race/ethnicity, marital status, and general health.
      CONCLUSION: A very strong apparent relationship between concern about enough food
      and obesity could be entirely accounted for by the influences of socioeconomic
      variables. This emphasizes the need for longitudinal research studies using
      precise measures of weight, height, and food security.

PMID- 14715210
TI  - To screen or not to screen, when clinical guidelines disagree: primary care
      physicians' use of the PSA test.
AB  - BACKGROUND: Clinical guidelines for using the prostate-specific antigen (PSA)
      test as a population-based screening tool vary considerably. This study
      qualitatively explored primary care physicians' PSA screening practices and their
      understanding of the PSA screening controversy. METHODS: Fourteen telephone focus
      groups were conducted with 75 primary care physicians practicing in 35 US states.
      Data were coded around three major topics: PSA screening practices, factors
      influencing these practices, and familiarity with clinical guidelines. RESULTS:
      Two practice patterns emerged. Most participants recommended regular PSA
      screening beginning around age 50 for asymptomatic men with no known risk factors
      and at least a 10-year life expectancy. These "routine screeners" attributed
      their approach to experience that supported the benefit of PSA screening and to
      patient demand for the test. Other physicians discussed the implications of PSA
      screening with patients before offering the test, but neither recommended for or
      against it. The approach of these "nonroutine screeners" was primarily guided by
      the lack of scientific evidence documenting the benefit of PSA screening.
      CONCLUSIONS: The observed practice patterns reflect both sides of the PSA
      screening controversy. While routine and nonroutine screeners differ in their
      approach, both reported high rates of PSA screening.

PMID- 14715211
TI  - Cervical cancer screening beliefs among young Hispanic women.
AB  - OBJECTIVES: This study examined beliefs, attitudes, and personal characteristics
      that correlated with self-reported cervical cancer screening history among
      Hispanic women aged 18 to 25 years old in El Paso, TX, a large metropolitan area
      on the U.S.-Mexico border. METHODS: Data were collected through a cross
      sectional, face-to-face survey. The study questionnaire was based primarily on
      the Health Belief Model, and included scales that measured perceived
      susceptibility and seriousness of cervical cancer, and perceived benefits and
      barriers to Pap test screening. The study questionnaire also included measures of
      acculturation, Pap test history, pregnancy and sexual history, use of birth
      control, type of medical insurance, and educational attainment. RESULTS: Sixty
      nine percent reported ever having had a Pap test and 56% reported having had a
      test in the past year. Eighty percent reported that they were sexually active,
      and of these, 63% reported using birth control. Respondents understood the
      seriousness of cervical cancer, their susceptibility to cervical cancer, and the
      benefits of Pap testing; however, only 61% agreed that most young women whom they
      know have Pap tests. Greater acculturation and the belief that most young
      unmarried women have Pap tests were positively associated with ever having
      screening. The perception that the test would be painful and not knowing where to
      go for the test were negatively associated with ever having a Pap test.
      CONCLUSIONS: This study found suboptimal rates of screening for cervical cancer
      in a sample of young Hispanic women residing along the U.S.-Mexico border.
      Although women may understand the seriousness of cervical cancer and the benefits
      of screening, perceptions about Pap tests may pose barriers to undergoing
      screening. Efforts to increase screening also may need to focus specifically on
      women who are least acculturated, as they also were least likely to have had
      prior Pap tests.

PMID- 14715212
TI  - Direct observation of physician counseling on dietary habits and exercise:
      patient, physician, and office correlates.
AB  - BACKGROUND: This study documented the frequency and correlates of directly
      observed physicians' counseling on dietary habits and exercise in private medical
      practices. METHODS: Trained medical students observed physician, office, and
      patient characteristics in 4344 patient visits in 38 nonmetropolitan primary care
      physician offices. RESULTS: Counseling rates ranged from 0% in some offices to
      55% in others. Physicians counseled patients on dietary habits in 25% of visits
      and exercise in 20% of visits. Physicians counseled new patients 30% more often
      than established ones (P < 0.05). Dietary counseling was associated with having
      dietary and exercise brochures in the office (P < 0.05). When counseling
      occurred, physicians (rather than patients) initiated both dietary and exercise
      counseling 61% of the time. Counseling for dietary habits was associated with
      counseling for exercise (P < 0.05); some physicians may be more likely to give
      preventive counseling. Counseling was not associated with physicians' age, years
      in practice, or number of patients per week. CONCLUSION: Physician counseled
      patients in 20-25% of visits, and this was not affected by physician
      characteristics. Results suggest that physician counseling protocols and other
      office prompts should be developed and promoted. Strategies targeting both
      physician and the health care system may improve the consistency of physician
      preventive counseling practices.

PMID- 14715213
TI  - Are persons with diabetes practicing healthier behaviors in the year 2001?
      Results from the Behavioral Risk Factor Surveillance System.
AB  - BACKGROUND: To examine changes in modifiable health-risk behaviors of diabetic
      persons in the United States. METHODS: A cross-sectional study was conducted of
      noninstitutionalized adults aged 18 years or older, in states that participated
      in the Behavioral Risk Factor Surveillance System in 1995 and 2001. Changes in
      self-reported health-risk behaviors among persons with diabetes are examined for
      those years (5,218 in 1995 and 13,733 in 2001 for the core instrument; 3,227 in
      1995 and 9,304 in 2001 for the diabetes module). RESULTS: From 1995 to 2001, the
      percentage of persons with diabetes who were obese, had ever been told their
      blood pressure or blood cholesterol was high, or had their blood cholesterol
      checked in the past year increased significantly. Significant increases were also
      reported among diabetic persons who were former smokers, received an annual
      influenza vaccination, ever received a pneumococcal vaccination, performed daily
      self-monitoring of blood glucose, received annual foot examination, and received
      annual dilated eye exam. CONCLUSIONS: Continued emphasis needs to be placed on a
      multirisk factor approach to prevent, delay, and reduce the complications of
      diabetes.

PMID- 14715214
TI  - The Group-Based Medical Mistrust Scale: psychometric properties and association
      with breast cancer screening.
AB  - BACKGROUND: There is little research on medical mistrust as a barrier to breast
      cancer screening. This study investigated the psychometric properties of a new
      scale, the Group-Based Medical Mistrust Scale (GBMMS), and its association with
      cancer screening attitudes and breast cancer screening practices among African
      American and Latina women. METHODS: Participants were 168 African American and
      Latina urban women who completed the GBMMS and measures of sociodemographics,
      cancer screening pros and cons, acculturation, breast cancer screening practices
      and physician recommendation of such screening. RESULTS: A principal components
      analysis of GBMMS items revealed three factors that were analyzed as subscales:
      (1) suspicion, (2) group disparities in health care, and (3) lack of support from
      health care providers. Convergent validity of the GBMMS was supported by its
      negative association with perceived benefits of cancer screening and
      acculturation and positive association with perceived disadvantages of cancer
      screening. Results further showed that women who reported no previous mammogram
      or a long-term lapse in mammography participation (>5 years) had significantly
      higher total GBMMS scores (P < 0.04) compared to women who were either adherent
      to mammography guidelines or nonadherent but reported a mammogram within the past
      5 years. This analysis controlled for physician recommendation. CONCLUSIONS:
      Results support the validity of the GBMMS and its association with breast cancer
      screening adherence. The GBMMS may be used to further investigate medical
      mistrust as a barrier to screening for cancers for which ethnic group disparities
      have been observed.

PMID- 14715215
TI  - The effect of office-based physician's advice on adolescent exercise behavior.
AB  - BACKGROUND: This study examines whether the adolescents' current levels of
      physical activity are increased by their physicians' advice provided in the
      office, in accordance with the American Medical Association recommendation.
      METHODS: The first adolescent (12-21 years old) of whichever age and gender,
      passing through six family physicians' offices during a 6-month period was
      assigned to the intervention group, and the second adolescent of the same age and
      gender was assigned to the control group. Each patient was classified as active,
      partially active, and inactive, according to how they answered the questions
      about their physical activity levels, and patients in the intervention group were
      then provided with reinforcement, increase, or initiation counseling,
      respectively. Identical procedures were repeated at the 6- and 12-month office
      visits. Changes in prevalence of activity, as well as, duration, frequency, and
      intensity of exercise and/or sports were verified at each visit. RESULTS: Of the
      87.5% of the original sample that completed the survey, 6- and 12-month data were
      available for 70.1%. Among the 392 adolescents that finished the study, those
      provided with counseling had 41.5% more active adolescents, as well as 26.8%,
      38.0% and 26.2% higher duration, frequency and intensity, respectively, than the
      control group. CONCLUSIONS: The proportion of active adolescents, as well as, the
      duration, frequency and intensity of leisure time exercise and/or sports are
      increased by physician advice.

PMID- 14715216
TI  - What respondents recall about walking and what self-report items elicit about
      walking.
AB  - BACKGROUND: Research on the cognitive processing of survey questions suggests
      that the distribution of walking bouts (e.g., mean, skew) may influence
      retrospective self-report responses. METHODS: Undergraduate women (N = 209) kept
      a weekly log of their walking behavior, then responded to four different self
      report measures of walking [National Health Interview Survey (NHIS), Context,
      Fuzzy-Typical, and Fuzzy-Maximum]. The logs were evaluated to determine which
      walking characteristics best summarized their walking behavior. Principal
      components analysis yielded three components of walking behaviors: Frequency,
      Duration, and Maximum. Multiple regression was used to determine if the walking
      components differentially predicted the four self-report measures of walking.
      RESULTS: The Maximum walking component was a significant predictor of all self
      report measures of walking. The Context score was also predicted by the Frequency
      Component. The Frequency and Duration walking components did not predict the NHIS
      or Fuzzy self-report measures independently of Maximum walking. CONCLUSIONS:
      Frequency-by-duration self-report measures of walking appear to be more sensitive
      to the maximum rather than the frequency or duration of walking behavior.
      Measurement of the frequency of bouts may be best accomplished by providing a
      framework of recall cues around which walks of different types occur.

PMID- 14715217
TI  - Cost effectiveness of a bicycle/pedestrian trail development in health promotion.
AB  - BACKGROUND: A persistently low population level of physical activity is a
      challenge for public health. Data on cost effectiveness of environmental
      interventions are needed to inform the development and implementing of such
      interventions. OBJECTIVE: To conduct cost-effectiveness analysis of
      bicycle/pedestrian trails. DESIGN: The costs of trail development and number of
      users of four trails in Lincoln, NE, were obtained. The costs were adjusted to
      2003 dollars. The physical activity-related outcomes/items are number of users
      who were more physically active since they began using the trails, number of
      users who were physically active for general health, and number of users who were
      physically active for weight loss. Cost-effectiveness measures were derived.
      Sensitivity analysis was performed. RESULTS: The annual trail development cost
      US$289,035, 73% of which was construction cost. Of the 3,986 trail users, 88%
      were active at least 3 days a week. The average annual cost for persons becoming
      more physically active was US$98 (range US$65-253); the cost was US$142 (range
      US$95-366) for persons who are active for general health, and US$884 (range
      US$590-2,287) for persons who are active for weight loss. CONCLUSION: This
      analysis provides basic cost-effectiveness measures of bicycle/pedestrian trails.
      Policymakers can use this information in making resource allocation decisions.

PMID- 14715218
TI  - Eating out in America, 1987-2000: trends and nutritional correlates.
AB  - BACKGROUND: Despite widely held beliefs about increasing popularity of eating
      away-from-home and its possible contribution to increasing adiposity of the US
      population, there are little published data on this topic. To address this issue,
      we examined trends in frequency of consumption of commercially prepared (CP)
      meals reported by Americans aged > or =18 years, and its nutritional correlates.
      METHODS: The data were from the National Health Interview Survey (NHIS) 1987 (n =
      21,731), NHIS 1992 (n = 11,718), and the National Health and Nutrition
      Examination Survey (NHANES) 1999-2000 (n = 5,330). The information on CP meal
      consumption was obtained from questions included in the three surveys. The
      independent association of reported CP meal frequency with body mass index (BMI),
      and intakes of energy and macronutrients was examined using multiple linear
      regression methods. RESULTS: The mean reported number of CP meals per week was
      2.5 in 1987 and 1992, and 2.8 in 1999-2000. In 1987, approximately 28% of the
      population reported 0 or <1 commercially prepared meal per week, decreasing to
      24% in 1999-2000 (P for trend <0.0001). However, the proportion of the population
      reporting three or more weekly CP meals increased from 36% in 1987 to 41% in 1999
      2000 (P for trend < or =0.0005). The odds of eating out at least one or more and
      three or more meals per week were 40% higher (95% CI 1.20-1.70) in 1999-2000
      relative to 1987. The reported number of CP meals per week was positively
      associated with estimates of energy intake (P < or = 0.0001) in each survey. Self
      reported and measured BMI were modestly associated with the reported number of
      weekly CP meals in women in 1999-2000 (P < or = 0.05). CONCLUSION: Our results
      confirm that in 1999-2000, more Americans ate out, and ate out more frequently
      than in 1987 and 1992. Higher eating-out frequency was associated with adverse
      nutritional consequences.

PMID- 14715219
TI  - The origin and evolution of seahorses (genus Hippocampus): a phylogenetic study
      using the cytochrome b gene of mitochondrial DNA.
AB  - Phylogenetic relationships among 93 specimens of 22 species of seahorses (genus
      Hippocampus) from the Atlantic and Indo-Pacific Oceans were analysed using
      cytochrome b gene sequence data. A maximum sequence divergence of 23.2% (Kimura 2
      parameter model) suggests a pre-Tethyan origin for the genus. Despite a greater
      number of seahorse species in the Indo-Pacific than in the Atlantic Ocean, there
      was no compelling genetic evidence to support an Indo-Pacific origin for the
      genus Hippocampus. The phylogenetic data suggest that high diversity in the Indo
      Pacific results from speciation events dating from the Pleistocene to the
      Miocene, or earlier. Both vicariance and dispersal events in structuring the
      current global distribution of seahorses. The results suggested that several
      species designations need re-evaluating, and further phylogeographic studies are
      required to determine patterns and processes of seahorse dispersal.

PMID- 14715220
TI  - The evolutionary history of seahorses (Syngnathidae: Hippocampus): molecular data
      suggest a West Pacific origin and two invasions of the Atlantic Ocean.
AB  - Sequence data derived from four markers (the nuclear RP1 and Aldolase and the
      mitochondrial 16S rRNA and cytochrome b genes) were used to determine the
      phylogenetic relationships among 32 species belonging to the genus Hippocampus.
      There were marked differences in the rate of evolution among these gene
      fragments, with Aldolase evolving the slowest and the mtDNA cytochrome b gene the
      fastest. The RP1 gene recovered the highest number of nodes supported by >70%
      bootstrap values from parsimony analysis and >95% posterior probabilities from
      Bayesian inference. The combined analysis based on 2317 nucleotides resulted in
      the most robust phylogeny. A distinct phylogenetic split was identified between
      the pygmy seahorse, Hippocampus bargibanti, and a clade including all other
      species. Three species from the western Pacific Ocean included in our study,
      namely H. bargibanti, H. breviceps, and H. abdominalis occupy basal positions in
      the phylogeny. This and the high species richness in the region suggests that the
      genus evolved somewhere in the West Pacific. There is also fairly strong
      molecular support for the remaining species being subdivided into three main
      evolutionary lineages: two West Pacific clades and a clade of species present in
      both the Indo-Pacific and the Atlantic Ocean. The phylogeny obtained herein
      suggests at least two independent colonization events of the Atlantic Ocean, once
      before the closure of the Tethyan seaway, and once afterwards.

PMID- 14715221
TI  - Birth-and-death evolution of protein-coding regions and concerted evolution of
      non-coding regions in the multi-component genomes of nanoviruses.
AB  - Genomes of the four plant viruses of the genus Nanovirus consist of multiple
      circular single-stranded DNA components, each of which encodes a single protein.
      Protein phylogenies supported the hypothesis that faba bean necrotic yellows
      virus (FBNYV) and milk vetch disease virus (MDV) are sister taxa; that
      subterranean clover stunt virus (SCSV) branched next; and that banana bunchy top
      virus (BBTV) is an outgroup to the three other species. The phylogeny of
      replication (Rep) proteins indicate that this small viral multi-gene family has
      evolved by a process of duplication and subsequent loss of Rep-encoding genome
      components, analogous to the "birth-and-death" process of evolution which has
      been described in eukaryotic multi-gene families. By contrast, repeated
      recombinational events between components were found to have homogenized the non
      coding portions of several components encoding unrelated components. For example,
      as result of recent recombination a portion of the non-coding region is virtually
      identical among SCSV components 1, 3, 4, 5, and 7. Thus, there is a process of
      concerted evolution of non-coding regions of Nanovirus genome components, which
      raises the possibility that certain non-coding regions are subject to functional
      constraint.

PMID- 14715222
TI  - High mitochondrial diversity within and among populations of Malagasy poison
      frogs.
AB  - The diurnal, brightly colored, and toxic frogs of the genus Mantella are among
      the most prominent representatives of the endemic anuran fauna of Madagascar.
      Especially three closely related species, M. aurantiaca, M. crocea, and M.
      milotympanum, are intensively collected for the pet trade, although basic data on
      their natural history and genetic diversity are still lacking. Our phylogenetic
      analyses based on 2.8 kbp of partial 16S rRNA, 12S rRNA, cytochrome b, and
      rhodopsin DNA sequences confirmed that these species belong to one of the five
      major clades in Mantella, the M. madagascariensis group. A haplotype network
      constructed using 830 bp of cytochrome b in 49 individuals from seven populations
      revealed that M. milotympanum and M. crocea have largely similar haplotypes
      sharing, confirming doubts about the species validity of M. milotympanum and
      indicating independent evolution of bright orange pattern in M. milotympanum and
      M. aurantiaca. Further, clustering of four individuals of M. aurantiaca from
      Andranomena with M. crocea suggests incomplete lineage sorting or introgression
      resulting from secondary contact of refugial populations. AMOVA confirmed
      significant intrapopulation nucleotide diversity (>20%). These diversity patterns
      and our field observations indicate relatively large population sizes. Hence,
      overcollecting is probably a minor problem and conservation efforts should rather
      focus on saving some large populations from habitat destruction through logging
      and forest fires.

PMID- 14715223
TI  - Analysis of mitochondrial D-loop region casts new light on domestic water buffalo
      (Bubalus bubalis) phylogeny.
AB  - The phylogeny of water buffaloes (Bubalus bubalis) is still a matter of
      discussion, especially if the two types of domestic water buffalo (swamp and
      river) derived from different domestication events or if they are products of
      human selection. To obtain more insight, we analyzed the entire mitochondrial D
      loop region of 80 water buffaloes of four different breeds, i.e., 19 swamp
      buffaloes (Carabao) and 61 river buffaloes (Murrah, Jafarabadi, and
      Mediterranean), sampled in Brazil and Italy. We detected 36 mitochondrial
      haplotypes with 128 polymorphic sites. Pooled with published data of South-East
      Asian and Australian water buffaloes and based on comprehensive median-joining
      network and population demography analyses we show evidence that both river and
      swamp buffaloes decent from one domestication event, probably in the Indian
      subcontinent. However, the today swamp buffaloes have an unravelled mitochondrial
      history, which can be explained by introgression of wild water buffalo mtDNA into
      domestic stocks. We are also discussing indications for an independent
      domestication of buffaloes in China.

PMID- 14715224
TI  - Molecular phylogeny of songbirds (Passeriformes) inferred from mitochondrial 16S
      ribosomal RNA gene sequences.
AB  - Phylogenetic relationships among the families of passerine birds have been the
      subject of many debates. These relationships have been investigated by using a
      number of different character sets, including morphology, proteins, DNA-DNA
      hybridization, and mitochondrial DNA gene sequences. Our objective was to examine
      the phylogenetic relationships of a set of passerine songbirds (Oscines) and to
      test the taxonomic relationships proposed by. We sequenced 1403 aligned bases
      encompassing the mitochondrial transfer-RNA-Valine and 16S ribosomal RNA genes in
      27 species from 14 families (including a Suboscine outgroup). Our results differ
      in significant ways from the superfamily designations of Sibley and Ahlquist by
      questioning the monophyly of the Sylvioidea and by placing the Regulidae in the
      Corvoidea.

PMID- 14715225
TI  - Phylogenetic relationships of Drosophila melanogaster species group deduced from
      spacer regions of histone gene H2A-H2B.
AB  - Nucleotide sequences of the spacer region of the histone gene H2A-H2B from 36
      species of Drosophila melanogaster species group were determined. The
      phylogenetic trees were reconstructed with maximum parsimony, maximum likelihood,
      and Bayesian methods by using Drosophila pseudoobscura as the out group. Our
      results show that the melanogaster species group clustered in three main
      lineages: (1). montium subgroup; (2). ananassae subgroup; and (3). the seven
      oriental subgroups, among which the montium subgroup diverged first. In the third
      main lineage, suzukii and takahashii subgroups formed a clade, while eugracilis,
      melanogaster, elegans, ficusphila, and rhopaloa subgroups formed another clade.
      The bootstrap values at subgroup levels are high. The phylogenetic relationships
      of these species subgroups derived from our data are very different from those
      based on some other DNA data and morphology data.

PMID- 14715226
TI  - Origin of a new Reticulitermes termite (Isoptera, Rhinotermitidae) inferred from
      mitochondrial and nuclear DNA data.
AB  - The Holoarctic termite genus Reticulitermes is widely distributed in Europe. A
      new Reticulitermes species, R. sp. nov, was recently found in France and Italy.
      Its phylogenetic position was investigated using a 743-bp fragment of
      mitochondrial 16S rRNA-ND1 genes and 382-bp of the nuclear ITS2 region.
      Phylogenies for these sequences were estimated by neighbor-joining, maximum
      parsimony and maximum-likelihood analysis. The results strongly supported a
      relationship between R. sp. nov. and the termite species from the eastern
      Mediterranean area including Reticulitermes balkanensis from the Balkans,
      Reticulitermes lucifugus from Turkey and Reticulitermes clypeatus from Israel.
      The hypothesis of a relationship between R. sp. nov. and the Japanese
      Reticulitermes speratus was rejected by parametric bootstrap. The current
      distribution of R. sp. nov. could be linked to postglacial colonization routes
      between Balkan refuge and northern regions.

PMID- 14715227
TI  - Phylogenetics of the southern African dwarf chameleons, Bradypodion (Squamata:
      Chamaeleonidae).
AB  - The taxonomic relationships within the dwarf chameleons (Bradypodion) of southern
      Africa have long been controversial. Although informal phenotypic groups have
      been suggested, the evolutionary relationships among the 15 recognised species in
      southern Africa have not been previously investigated. To investigate the
      relationships among species within this genus, fragments of two mitochondrial
      genes (16S ribosomal RNA and ND2) were sequenced and analysed using maximum
      parsimony, maximum likelihood and Bayesian inference. All analyses showed
      congruent topologies, revealing at least 5 well-supported clades distributed
      across distinct geographic regions. The mtDNA gene tree indicated that in many
      instances, geographic location has played a role in shaping the evolution of this
      group, and that the previously suggested phenotypic groupings do not adequately
      reflect evolutionary relationships. Furthermore, it appears that some of the
      currently recognised species (described on morphology) are polyphyletic for
      mitochondrial sequences, most notably those occurring in the isolated forest
      patches of north-eastern South Africa, near the Drakensberg Escarpment.

PMID- 14715228
TI  - Molecular phylogeny of the Gasterosteidae: the importance of using multiple
      genes.
AB  - The Gasterosteidae is an important model system in evolutionary biology.
      Phylogenetic relationships have previously been constructed based upon
      morphological and behavioral data, but to date no one has investigated those
      relationships using molecular characters. This paper reports the results of an
      analysis using sequences from five mitochondrial genes (12S rRNA, 16S rRNA,
      cytochrome b, ATPase 6, and control region). Phylogenetic analysis of 2879 bp
      produced a single most parsimonious tree with a consistency index of 72.6%. That
      tree agrees with the behavior+morphology topology, with one exception: Apeltes is
      placed as the sister group to Pungitius+Culaea, rather than as the sister-group
      of (Pungitius+Culaea)+Gasterosteus. This study highlights the importance of using
      multiple mitochondrial genes in a phylogenetic analysis. Separately, the five
      genes produced four significantly different topologies, and might have given
      different versions of gasterosteid relationships had only one or two genes been
      sequenced. It is thus imperative that comparative biologists choose only trees
      that contain multiple mitochondrial genes as the basis for studies of
      evolutionary patterns and processes.

PMID- 14715229
TI  - Molecular phylogenetic relationships among Lemnaceae and Araceae using the
      chloroplast trnL-trnF intergenic spacer.
AB  - We test competing hypotheses of relationships among Aroids (Araceae) and
      duckweeds (Lemnaceae) using sequences of the trnL-trnF spacer region of the
      chloroplast genome. Included in the analysis were 22 aroid genera including
      Pistia and five genera of Lemnaceae including the recently segregated genus
      Landoltia. Aponogeton was used as an outgroup to root the tree. A data set of 522
      aligned nucleotides yielded maximum parsimony and maximum likelihood trees
      similar to those previously derived from restriction site data. Pistia and the
      Lemnaceae are placed in two separate and well-supported clades, suggesting at
      least two independent origins of the floating aquatic growth form within the
      aroid clade. Within the Lemnaceae there is only partial support for the paradigm
      of sequential morphological reduction, given that Wolffia is sister to
      Wolffiella+Lemna. As in the results of the restriction site analysis, pantropical
      Pistia is placed with Colocasia and Typhonium of southeastern Asia, indicative of
      Old World affinities. Branch lengths leading to duckweed terminal taxa are much
      longer relative to other ingroup taxa (including Pistia), evidently as a result
      of higher rates of nucleotide substitutions and insertion/deletion events.
      Morphological reduction within the duckweeds roughly correlates with accelerated
      chloroplast genome evolution.

PMID- 14715230
TI  - Nuclear and mitochondrial DNA evidence of polyphyly in the avian superfamily
      Muscicapoidea.
AB  - Nucleotide sequences of the nuclear c-mos gene and the mitochondrial cytochrome b
      and ND2 genes were used to assess the monophyly of Sibley and Monroe's
      [Distribution and Taxonomy of Birds of the World, Yale University Press, New
      Haven, 1990] Muscicapoidea superfamily. The relationships and monophyly of major
      lineages within the superfamily, as well as genera membership in major lineages
      was also assessed. Analyses suggest that Bombycillidae is not a part of
      Muscicapoidea, and there is strongly supported evidence to suggest that Turdinae
      is not part of the Muscicapidae, but is instead sister to a Sturnidae+Cinclidae
      clade. This clade is in turn sister to Muscicapidae (Muscicapini+Saxicolini). Of
      the 49 Turdinae and Muscicapidae genera that we included in our analyses, 10
      (20%) are shown to be misclassified to subfamily or tribe. Our results place one
      current Saxicolini genus in Turdinae, two Saxicolini genera in Muscicapini, and
      five Turdinae and two Muscicapini genera in Saxicolini; these relationships are
      supported with 100% Bayesian support. Our analyses suggest that c-mos was only
      marginally useful in resolving these "deep" phylogenetic relationships.

PMID- 14715231
TI  - The phylogenetic relationships among Noturus catfishes (Siluriformes:
      Ictaluridae) as inferred from mitochondrial gene cytochrome b and nuclear
      recombination activating gene 2.
AB  - Madtom catfishes of the genus Noturus are a well-known component of the North
      American ichthyofauna. Original nucleotide sequence data were collected from
      mitochondrial (cytochrome b) and nuclear (recombination activating gene 2) genes
      and used to estimate genetic variation and infer phylogenetic relationships among
      and within species of Noturus. Mitochondrial sequences were variable among
      species and several species were found to contain considerable genetic diversity.
      Relationships among members of the subgenus Rabida were resolved and in many
      cases well supported. Relationships among members of the subgenus Schilbeodes
      were poorly resolved. Previous phylogenetic hypotheses and the traditional
      classification (except the furiosus species group) were rejected in their
      explicit form according to the Kishino-Hasegawa and Shimodaira-Hasegawa tests of
      tree score difference.

PMID- 14715232
TI  - Phylogenetic relationships of the North American chorus frogs (Pseudacris:
      Hylidae).
AB  - We examined phylogenetic relationships of the North American chorus frogs
      (Pseudacris: Hylidae) from 38 populations using 2.4 kb of 12S and 16S mtDNA to
      elucidate species relationships and examine congruence of previous phylogenetic
      hypotheses. Parsimony, maximum likelihood, and Bayesian phylogenies are
      consistent and reveal four strongly supported clades within Pseudacris: (1). A
      West Coast Clade containing regilla and cadaverina, (2). a Fat Frog Clade
      including ornata, streckeri, and illinoensis, (3). a Crucifer Clade consisting of
      crucifer and ocularis, and (4). a Trilling Frog Clade containing all other
      Pseudacris. Explicit hypothesis testing using parametric bootstrapping indicates
      that previous phylogenetic hypotheses are rejected by our sequence dataset.
      Within the Trilling Frog Clade, brimleyi and brachyphona form the sister group to
      the Nigrita Clade: nigrita, feriarum, triseriata, kalmi, clarkii, and maculata.
      The Nigrita Clade shows geographic division into three clades: (1). populations
      of maculata and triseriata west of the Mississippi River and Canadian
      populations, (2). southeastern US populations of feriarum and nigrita, and (3).
      northeastern US populations of feriarum, kalmi, and triseriata. We find that
      subspecific epithets for crucifer (crucifer and bartramiana) and nigrita (nigrita
      and verrucosa) are uninformative, therefore we discourage recognition of these
      subspecies. Pseudacris regilla, cadaverina, ocularis, and crucifer are maintained
      in Pseudacris.

PMID- 14715233
TI  - A molecular phylogeny of Amazona: implications for Neotropical parrot
      biogeography, taxonomy, and conservation.
AB  - Amazon parrots (Genus Amazona) are among the most recognizable and imperiled of
      all birds. Several hypotheses regarding the evolutionary history of Amazona are
      investigated using a combined phylogenetic analysis of DNA sequence data from six
      partitions including mitochondrial (COI, 12S, and 16S) and nuclear (beta-fibint7,
      RP40, and TROP) regions. The results demonstrate that Amazona is not monophyletic
      with respect to the placement of the Yellow-faced parrot (Amazona xanthops), as
      first implied by. In addition, the analysis corroborates previous studies
      suggesting a Neotropical short-tailed parrot genus as sister to Amazona. At a
      finer level, the phylogeny resolves the Greater Antillean endemic species as
      constituting a monophyletic group, including the Central American Amazona
      albifrons, while further revealing a paraphyletic history for the extant Amazon
      species of the Lesser Antilles. The reconstructed phylogeny provides further
      insights into the mainland sources of the Antillean Amazona, reveals areas of
      taxonomic uncertainty within the genus, and presents historical information that
      may be included in conservation priority-setting for Amazon parrots.

PMID- 14715234
TI  - Molecular phylogeny of Zygomycota based on EF-1alpha and RPB1 sequences:
      limitations and utility of alternative markers to rDNA.
AB  - Earlier molecular phylogenetic analyses based on nuclear small subunit ribosomal
      DNA (nSSU rDNA) suggest that the Zygomycota are polyphyletic within the
      Chytridiomycota. However, these analyses failed to resolve almost all
      interordinal relationships among basal fungi (Chytridiomycota and Zygomycota),
      due to lack of sufficient characters within the nSSU rDNA. To further elucidate
      the higher-level phylogeny of Zygomycota, we have sequenced partial RPB1 (DNA
      dependent RNA polymerase II largest subunit) and EF-1alpha (translation
      elongation factor 1 alpha) genes from 10 and 3 zygomycete fungi, respectively.
      Independent molecular phylogenetic analyses were performed based on each sequence
      by distance and maximum likelihood methods. Although deep phylogenetic
      relationships among basal fungi still remain poorly resolved using either gene,
      the RPB1-based phylogeny identified a novel monophyletic clade consisting of the
      Dimargaritales, Harpellales, and Kickxellales. This result suggests that
      regularly formed septa (cross walls that divide hyphae into segments) with a
      lenticular cavity are plesiomorphic for this clade, and indicates the importance
      of septal pore ultrastructure in zygomycete phylogeny. In addition, a peculiar
      mucoralean genus Mortierella, which was considered to be distantly related to the
      other Mucorales based on previous nSSU rDNA analyses, was resolved as the basal
      most divergence within the Mucorales, consistent with traditional phenotypic
      based taxonomy. Although the taxa included in our analysis are restricted, the
      monophyly of each order suggested by nSSU rDNA phylogeny is supported by the
      present RPB1-based analysis. These results support the potential use of RPB1 as
      an alternative marker for fungal phylogenetic studies. Conversely, the overall
      fungal phylogeny based on EF-1alpha sequence is poorly resolved. A comparison of
      numbers of observed substitutions versus inferred substitutions within EF-1alpha
      indicates that this gene is much more saturated than RPB1. This result suggests
      that the EF-1alpha gene is unsuitable for resolving higher-level phylogenetic
      relationships within the Fungi.

PMID- 14715235
TI  - Molecular phylogeny and biogeography of the Korean woodroaches Cryptocercus spp.
AB  - Phylogenetic relationships and biogeography of Northeast Asian Cryptocercus were
      inferred based on the DNA sequences of mitochondrial COII and 16S rRNA genes and
      nuclear 18S rRNA gene. The results suggest that two clades exist in Korean
      populations. The southwestern population (Cryptocercus from Jiri-san) was more
      closely related to the populations from Northeast China and eastern Russia than
      to all the other Korean Cryptocercus. According to molecular-based estimated
      divergence times, the divergence event occurred between Cryptocercus in Jiri-san,
      Northeast China and eastern Russia and those in the remaining South Korea during
      the Miocene (7.5-17.4Myr ago), and then the divergence event between Cryptocercus
      in Jiri-san and those in Northeast China and eastern Russia occurred 0.8-1.9Myr
      ago. In the Korean Peninsula, Jiri-san is located in the most southwestern region
      among the high mountains surveyed. The location is the farthest from Northeast
      China and eastern Russia among sampling localities in South Korea. Thus, it was
      unexpected that the southwestern populations are more closely related to those
      from Northeast China and eastern Russia rather than to the other Korean
      Cryptocercus. Based on Korean topography and estimated divergence times, possible
      scenarios are proposed for the current geographical distribution of Korean
      Cryptocercus.

PMID- 14715236
TI  - Phylogeny of holoparasitic Orobanche (Orobanchaceae) inferred from nuclear ITS
      sequences.
AB  - Orobanche is the largest genus among the holoparasitic members of Orobanchaceae.
      We present the first molecular phylogenetic analysis (using nuclear ITS
      sequences) that includes members of all sections of Orobanche, Gymnocaulis,
      Myzorrhiza, Trionychon, and Orobanche. Orobanche is not monophyletic, but falls
      into two lineages: (1) the Orobanche group comprises Orobanche sect. Orobanche
      and the small Near Asian genus Diphelypaea and is characterized by a chromosome
      base number of x=19 and (2) the Phelipanche group contains Orobanche sects.
      Gymnocaulis, Myzorrhiza, and Trionychon and possesses a chromosome base number of
      x=12. The relationships between these two groups and to other genera such as
      Boschniakia or Cistanche remain unresolved. Within the Orobanche group, Orobanche
      macrolepis and Orobanche anatolica (including Orobanche colorata) constitute two
      phylogenetically distinct lineages. Intrasectional structurings proposed by some
      authors for O. sect. Orobanche are not confirmed by the molecular data. In most
      cases, intraspecific sequence divergence between accessions, if present, is
      negligible and not correlated with morphological or ecological traits. In a few
      cases, however, there is evidence for the presence of cryptic taxa.

PMID- 14715237
TI  - Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts:
      continuing uncertainties.
AB  - An analysis is made of the rate constants for the reactions involving the
      interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al.
      [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a
      reasonable rate of nucleotide exchange sufficient to support rates of protein
      synthesis in vivo, their data underestimate the thermodynamic barrier involved in
      nucleotide exchange and therefore cannot be considered definitive. A kinetic
      scheme consistent with the thermodynamic barrier can be achieved by modification
      of various rate constants, particularly of those involving the release of EF-Ts
      from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are
      experimentally observed. It thus remains impossible at present satisfactorily to
      model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double
      displacement mechanism, with experimentally derived rate constants. Metabolic
      control analysis has been applied to determine the degree of flux control of the
      different steps in the pathway.

PMID- 14715238
TI  - A monomer form of the glutathione S-transferase Y7F mutant from Schistosoma
      japonicum at acidic pH.
AB  - Dissociation and unfolding of homodimeric glutathione S-transferase Y7F mutant
      from Schistosoma japonicum (SjGST-Y7F) were investigated at equilibrium using
      urea as denaturant. The conserved residue Tyr7 plays a central role in the
      catalytic mechanism and the mutation Tyr-Phe yields an inactive enzyme that is
      able to bind the substrate GSH with a higher binding constant than the wild type
      enzyme. Mutant SjGST-Y7F is a dimer at pH 6 or higher and a stable monomer at pH
      5 that binds GSH (K value of 1.2x10(5)+/-6.4x10(3)M(-1) at pH 6.5 and 6.3x10(4)+/
      1.25x10(3)M(-1) at pH 5). The stability of the SjGST-Y7F mutant was studied by
      urea induced unfolding techniques (DeltaG(W)=13.86+/-0.63kcalmol(-1) at pH 6.5
      and DeltaG(W)=11.22+/-0.25kcalmol(-1) at pH 5) and the monomeric form
      characterized by means of size exclusion chromatography, fluorescence, and
      electrophoretic techniques.

PMID- 14715239
TI  - Non-helical type IV collagen polypeptides in human placenta.
AB  - Our previous reports showed that cultured human cells secrete non-disulfide
      bonded non-helical alpha1(IV) and alpha2(IV) chains under physiological
      conditions. In the present report we show that the alpha(IV) chains in non
      helical form were reactive to lectin ABA (Agaricus bisporus agglutinin), whereas
      the alpha(IV) chains secreted in triple-helical form were not. These results
      indicate that ABA could be used to distinguish the two conformational isomers of
      type IV collagen polypeptides. An alpha1(IV) chain isolated from human placenta
      with an antibody-coupled column showed a positive reaction to ABA, indicating
      that gelatin form of the type IV collagen alpha1(IV) chain is produced and
      retained in the tissue in vivo. A possible significance of the gelatin form is
      discussed from the finding that the non-helical alpha1(IV) chain purified with
      EDTA-free buffer contained degraded polypeptides including NC1-size domain and
      showed an apparent inhibition against activated pro-MMP-9. This is the first
      report to show that a gelatin form of protein exists in vivo.

PMID- 14715240
TI  - Differential regulation of alpha6beta4 integrin by PKC isoforms in murine skin
      keratinocytes.
AB  - In mammalian epidermis, alpha6beta4 integrin is expressed exclusively on the
      basal layer localized to the hemidesmosomes, where it interacts extracellularly
      with the laminin-5 ligand. During differentiation, loss of alpha6beta4 is
      associated with keratinocyte detachment from the basement membrane and upward
      migration. The protein kinase C (PKC) family of isoforms participates in
      regulation of integrin function and is linked to skin differentiation. Exposure
      of primary murine keratinocytes to PKC activators specifically downregulates
      alpha6beta4 expression. Utilizing recombinant adenoviruses, we selectively
      overexpressed skin PKC isoforms in primary keratinocytes. PKCdelta and PKCzeta
      induced downregulation of alpha6beta4 protein expression, leading to reduced
      keratinocyte attachment to laminin-5 and enhanced gradual detachment from the
      underlying matrix. In contrast, PKCalpha upregulated alpha6beta4 protein
      expression, leading to increased keratinocyte attachment to laminin-5 and to the
      underlying matrix. Altogether, these results suggest distinct roles for specific
      PKC isoforms in alpha6beta4 functional regulation during the early stages of skin
      differentiation.

PMID- 14715241
TI  - Vitamin K2 and geranylgeraniol, its side chain component, inhibited osteoclast
      formation in a different manner.
AB  - We comparatively examined the mechanism by which vitamin K(2) (Menatetrenone,
      MK4) and its side chain component, geranylgeraniol (GGO), inhibited osteoclast
      formation in the co-culture system of stromal cells with spleen cells. Both MK4
      and GGO inhibited osteoclast formation induced by 1alpha,25-dihydroxyvitamin D3
      (1,25(OH)(2)D(3)). MK4, but not GGO, inhibited cyclooxygenase-2 (COX-2)
      expression and prostaglandin E(2) (PGE(2)) production in the co-culture system.
      To elucidate the precise mechanism of the inhibitory effect of GGO on osteoclast
      formation, the co-cultured cells were stimulated with PGE(2). GGO, but not MK4,
      inhibited osteoclast formation via suppression of the receptor activator of NF
      kappaB ligand (RANKL) expression. Moreover, GGO abolished the disruption of
      osteoclastic actin rings induced by nitrogen-containing bisphosphonate (N-BP),
      whereas MK4 did not affect it at all. These data suggest that MK4 inhibited
      osteoclast formation independently of GGO, and that MK4, but not GGO, has no
      competitive action on the anti-osteoporotic effect of N-BP.

PMID- 14715242
TI  - Opposite effects of prostaglandin-J2 on VEGF in normoxia and hypoxia: role of HIF
      1.
AB  - The vascular endothelial growth factor (VEGF) is produced in response to hypoxia
      or inflammatory cytokines. In normoxia VEGF synthesis is upregulated by 15-deoxy
      Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) via induction of heme oxygenase-1
      (HO-1). Here we compared the influence of 15d-PGJ(2) on VEGF expression in human
      microvascular endothelial cells in normoxia (approximately 20% O(2)) and hypoxia
      ( approximately 2% O(2)). Regardless of the oxygen concentration, 15d-PGJ(2)
      inhibited activity of hypoxia inducible factor-1 (HIF-1), the major hypoxic
      regulator of VEGF. However, in normoxic conditions 15d-PGJ(2) (1-10microM)
      activated the VEGF promoter and increased synthesis of the VEGF protein.
      Concomitantly, it strongly induced expression of HO-1. In contrast, in hypoxia,
      15d-PGJ(2) decreased VEGF promoter activity and reduced VEGF release by 50%.
      Inhibition of HO-1 activity additionally attenuated VEGF synthesis in hypoxia. We
      conclude that induction of HO-1 by 15d-PGJ(2) results in augmentation of VEGF
      synthesis in normoxia. In hypoxia, however, the stimulatory effect of HO-1 is
      outweighed by 15d-PGJ(2)-mediated inhibition of the HIF-1 pathway.

PMID- 14715243
TI  - Nuclear import of N-terminal FAK by activation of the FcepsilonRI receptor in RBL
      2H3 cells.
AB  - As FAK integrates membrane receptor signalling, yet is also found in the nucleus,
      we investigated whether nuclear FAK is regulated by membrane receptor activation.
      Activation of the mast cell FcepsilonRI receptor leads to the release and
      synthesis of inflammatory mediators as well as increased proliferation and
      survival. Using RBL-2H3 basophilic leukaemia cells, FAK and the FcepsilonRI
      receptor were co-localised following cross-linking of IgE with antigen. This also
      resulted in a significant increase in the nucleus of several N-terminal FAK
      fragments, the largest of which included the kinase domain but not the focal
      adhesion targeting domain. This was confirmed using cells that stably expressed
      recombinant EGFP-FAK. Furthermore, treatment of EGFP-FAK expressing cells with
      Leptomycin B, an inhibitor of nuclear export, resulted in increased nuclear
      localisation of EGFP-FAK. Therefore, FAK can shuttle between the nuclear and
      cytoplasmic compartments and the cellular distribution of N-terminal FAK is
      regulated by membrane receptor activation.

PMID- 14715244
TI  - Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing
      markers in mouse body.
AB  - Photoluminescent semiconductor quantum dots (QDs) are novel nanometer-size probes
      that have found bioimaging. Here we imaged a cell line of mouse lymphocytes. QDs
      were actively taken into the target cells by endocytotic pathways. The
      fluorescence of QDs held in the endosomes could be studied for more than a week
      and remained stable luminescence against cell activation induced by concanavalin
      A, phytohemagglutinin, phorbol myristate acetate, and calcium ionophore A23187.
      These results suggested that QD-labeling was stable and did not affect either
      cell activation or cell function. When QD-labeled cells were intravenously
      injected into mouse, they remained in the peripheral blood in a concentration of
      approximately 10% up to 5 days after injection using both fluorescence microscopy
      and flow cytometry. In addition, approximately 20% of QDs were detected in the
      kidneys, liver, lung, and spleen and could still be observed 7 days after
      injection. These results suggested that fluorescent probes of QDs might be useful
      as bioimaging tools for tracing target cells over the period of a week in vivo.

PMID- 14715245
TI  - Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases.
AB  - We have identified and cloned 22 human cDNAs encoding novel members of the
      ubiquitin-specific protease (USP) family. Eighteen of the identified proteins
      contain all structural features characteristic of these cysteine proteinases,
      whereas four of them have been classified as non-peptidase homologues. Northern
      blot analysis demonstrated that the identified USPs are broadly and
      differentially distributed in human tissues, some of them being especially
      abundant in skeletal muscle or testis. Enzymatic studies performed with the
      identified USPs revealed that at least twelve of them are deubiquitylating
      enzymes based on their ability to cleave ubiquitin from a ubiquitin-beta
      galactosidase fusion protein. These results provide additional evidence of the
      extreme complexity and diversity of the USP proteolytic system in human tissues
      and open the possibility to explore the relevance of their multiple components in
      the regulation of ubiquitin-mediated pathways in normal and pathological
      functions.

PMID- 14715246
TI  - siRNA knock-down of gamma-glutamyl transpeptidase does not affect hypoxic K+
      channel inhibition.
AB  - Large conductance, Ca(2+)-sensitive potassium (BK) channels are critical
      components of the O(2) signalling cascade in a number of cells, including the
      carotid body and central neurones. Although the nature of the BK channel O(2)
      sensor is still unknown, evidence suggests redox modulators might form part of
      the O(2) sensing channel complex. By metabolising glutathione, gamma-glutamyl
      transpeptidase (gammaGT) could act as such an O(2) sensor. Western blotting and
      immunocytochemistry revealed high gammaGT expression in HEK293 cells expressing
      the alpha- and beta-subunits of human recombinant BK and gammaGT co
      immunoprecipitated with BKalpha. Acivicin blockade of gammaGT reversibly
      inhibited BK channels, suggesting that this BKalpha protein partner contributes
      to tonic channel activity. However, knock-out of gammaGT using siRNA had no
      effect on hypoxic BK channel inhibition. Together, these data indicate that
      gammaGT is a BKalpha protein partner, that its activity regulates BK channels but
      that it is not the BK O(2) sensor.

PMID- 14715247
TI  - Androgen suppresses PML protein expression in prostate cancer CWR22R cells.
AB  - The ability of PML to modulate key suppressive pathways in tumor cells suggests
      that PML may act as a tumor suppressor. The detailed mechanism of how PML
      functions in prostate cancer progression, however, remains unknown. Here we
      demonstrate that in the presence of androgen, PML protein expression can be
      suppressed in CWR22R prostate cancer cells. Further studies reveal that PML can
      selectively suppress AR transactivation and PML protein expression positively
      correlates with increased p21 protein level and enhances p53 transcription
      ability in CWR22R cells. We also found that PML strongly inhibits CWR22R cell
      colony formation, while PML siRNA enhances AR activity and CWR22R cell colony
      formation. Together our results suggest that PML may suppress prostate cancer
      cell growth by inhibiting AR transactivation and/or enhancing p53 activity.

PMID- 14715248
TI  - Induction of hepatoma cells migration by phosphoglucose isomerase/autocrine
      motility factor through the upregulation of matrix metalloproteinase-3.
AB  - Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) catalyzes the
      isomerization between glucose-6-phosphate and fructose-6-phosphate, and is
      involved in cytokine activity, mitogenesis, differentiation, oncogenesis, and
      tumor metastasis. Presently, we demonstrate that exogenous PGI/AMF stimulates the
      migration of Huh7 and HepG2 hepatoma cells, but not Hep3B cells. Inhibition of
      PGI/AMF by PGI/AMF specific inhibitor 5-phospho-D-arabinonate markedly repressed
      the cellular migration. RT-PCR was used to examine the expression profile of
      matrix metalloproteinases (MMPs). MMP-3 transcripts, protein level, and secreted
      form were significantly upregulated in PGI/AMF-treated Huh7 and HepG2 cells, but
      not in Hep3B cells. MMP-3 inhibition abolished the PGI/AMF-induced cell motility.
      The observations are consistent with a downstream mediation role of MMP-3 in
      PGI/AMF-stimulated tumor cell metastasis.

PMID- 14715249
TI  - Insulin-like growth factor binding protein-3 prevents retinoid receptor
      heterodimerization: implications for retinoic acid-sensitivity in human breast
      cancer cells.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) has both IGF-dependent and
      -independent effects on cell growth, which are frequently growth-inhibitory.
      Interestingly, the development of a more aggressive phenotype in breast cancer
      cells (BCCs) correlates positively with elevated expression of IGFBP-3 and is
      often associated with all-trans-retinoic acid (atRA)-resistance. IGFBP-3 was
      previously demonstrated to interact directly with retinoid X receptor (RXR). In
      this study we have shown that IGFBP-5 also interacts with RXR and that both
      IGFBPs interact with retinoic acid receptor (RAR). To investigate whether the
      presence of IGFBP-3 regulates breast cancer cell responsiveness to atRA, we
      immuno-neutralized the IGFBP-3 expressed by the atRA-resistant Hs578T and MDA-MB
      231 BCCs (which express IGFBP-3 constitutively) and showed that they become more
      sensitive to the growth-inhibitory effects of atRA. Similarly, in Hs578T cells
      expressing a reporter gene under the control of an RAR response element (RARE),
      depletion of IGFBP-3 resulted in the induction of reporter gene expression in
      response to atRA. In investigating possible mechanisms for IGFBP-3 regulation of
      atRA-sensitivity, we found that IGFBP-3 blocked the formation of RAR:RXR
      heterodimers and disrupted the ligand-inducible receptor complex. Thus, IGFBP-3
      has the potential to reduce the RARE-mediated transactivation of target genes and
      modulate the atRA-response in BCCs.

PMID- 14715250
TI  - Platelet-derived growth factor-BB modulates membrane mobility of beta1 integrins.
AB  - Platelet-derived growth factor (PDGF)-BB elicits a migratory response including
      reorganization of the actin cytoskeleton in different cell types. Here we have
      investigated the effects of PDGF-BB stimulation on beta(1) integrin containing
      focal adhesions in human diploid fibroblasts adhered to collagen type I.
      Stimulation with PDGF-BB dissociated focal adhesions and relocated beta(1)
      integrins from focal adhesions to the periphery of the cells. These changes were
      rapid and transient in character. Relocation of beta(1) integrins was prevented
      by inhibitors of phosphoinositide-3-kinase and protein kinase C. PDGF-BB
      stimulated fibroblasts exhibited an increased diffusion coefficient of cell
      surface beta(1) integrins as determined by fluorescence recovery of
      photobleaching. The cell surface expression of beta(1) integrins was not changed
      after stimulation with PDGF-BB. Our data suggest that PDGF-BB increases the
      dynamic properties of cell-surface beta(1) integrins, which most likely are
      important for the migratory response elicited by PDGF-BB.

PMID- 14715251
TI  - ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3.
AB  - ATBF1 was first discovered as a suppressor of AFP expression in hepatocytes. It
      is present in brain, adult liver, lung, and gastro-intestinal tract. Recently, it
      has been reported that ATBF1 regulates myoblastic differentiation and interacts
      with v-Myb in regulation of its transactivation. Using the yeast two-hybrid
      system, we searched for protein-protein interactions to uncover new functions for
      ATBF1. We present here experimental evidence that ATBF1 is a new regulatory
      factor for STAT3-mediated signal transduction through its interaction with PIAS3.
      PIAS3 was thus identified as an ATBF1-binding protein. In co-transfection
      experiments, the full-length ATBF1 was found to form complexes with PIAS3 in Hep
      G2 cells. In the luciferase assay, ATBF1 was found to have no influence on STAT3
      signaling induced by IL-6 stimulation, but it did synergistically enhance PIAS3
      inhibition of activated STAT3. In conclusion, ATBF1 can suppress the IL-6
      mediated cellular response by acting together with PIAS3.

PMID- 14715252
TI  - Induction of cytochrome CYP4F3A in all-trans-retinoic acid-treated HL60 cells.
AB  - Cytochrome P-450 CYP4F3A catalyzes the inactivation of leukotriene B(4) by omega
      hydroxylation, an activity of which is specifically expressed in human
      neutrophils. Here, we examined expression of the LTB(4) omega-hydroxylating
      activity during the differentiation of HL60 cells, an acute promyelocytic
      leukemia cell line, in the presence of various inducers. Among the inducers used,
      all-trans-retinoic acid (ATRA) most strongly induces the LTB(4) omega
      hydroxylating activity in a dose-dependent manner. The time course of the
      induction of the omega-hydroxylating activity correlates well with that of the
      superoxide-generating activity, indicative of cell differentiation. ATRA-treated
      cell microsomes convert LTB(4) to its 20-hydroxyl derivative under aerobic
      conditions in the present of NADPH. The reaction is inhibited by carbon monoxide,
      an inhibitor of cytochrome P-450, and by antibodies raised against NADPH-P-450
      reductase. CYP4F3A appears to be responsible for the LTB(4) omega-hydroxylase
      activity, based on the following observations: expression of the mRNA for CYP4F3A
      is observed together with the induction of LTB(4) omega-hydroxylating activity in
      ATRA-treated HL60 cells; and the apparent K(m) values for the omega-hydroxylation
      of LTB(4) and lipoxin B(4) by ATRA-treated cell microsomes are essentially the
      same as those of CYP4F3A in human neutrophil microsomes.

PMID- 14715253
TI  - Microarray-based method to evaluate the accuracy of restriction endonucleases
      HpaII and MspI.
AB  - A double-strand DNA (ds DNA) microarray was fabricated to analyze the structural
      perturbations caused by methylation and the different base mismatches in the
      interaction of the restriction endonucleases HpaII and MspI with DNA. First, a
      series of synthesized oligonucleotides were arrayed on the aldehyde-coated glass
      slides. Second, these oligonucleotides were hybridized with target sequences to
      obtain ds DNA microarray, which includes several types of double strands with the
      fully methylated, semi-methylated, and unmethylated canonical recognition
      sequences, semi-methylated and unmethylated base mismatches within the
      recognition sequences. The cleavage experiments were carried out under normal
      buffer conditions. The results indicated that MspI could partially cleave
      methylated and semi-methylated canonical recognition sequences. In contrast,
      HpaII could not cleave methylated and semi-methylated canonical recognition
      sequences. HpaII and MspI could both cleave the unmethylated canonical
      recognition sequence. However, HpaII could partially cleave the sequence
      containing one GG mismatch and not cleave other base mismatches in the
      corresponding recognition site. In contrast, MspI could not recognize the base
      mismatches within the recognition sequence. A good reproducibility was observed
      in several parallel experiments. The experiment indicates that the microarray
      technology has great potentials in high-throughput identifying important
      interactions between protein and DNA.

PMID- 14715254
TI  - In vitro methylation of nuclear respiratory factor-1 binding site suppresses the
      promoter activity of mitochondrial transcription factor A.
AB  - DNA methylation on CpG dinucleotides inactivates the expression of the many
      genes. The decreased amount of mitochondrial DNA (mtDNA) has been suggested to be
      an important indicator of mitochondrial biogenesis and the pathogenesis of many
      human diseases. Since mitochondria transcription factor A (Tfam) is a key
      molecule to regulate mtDNA replication and its promoter contains many CpG
      dinucleotides, potential methylation sites, we investigated whether the site
      specific methylation would modulate the Tfam promoter-driven transcriptional
      activity in vitro. The luciferase reporters ligated to Tfam promoter (pGL2
      Tfam2378) were in vitro methylated by SssI (CG), HpaII (CCGG), or HhaI (GCGC)
      methylase and luciferase activities were monitored after transient transfection
      of HepG2 cells. The SssI or HpaII methylation of pGL2-Tfam2378 or the SV40
      promoter-luciferase plasmid (pGL2-Control) decreased the luciferase activities to
      less than 10% of the unmethylated plasmids, indicating that this inactivation by
      SssI and HpaII methylation might not be specific for the Tfam promoter. In
      contrast, HhaI methylation of pGL2-Tfam2378 suppressed the promoter activity to
      24.4%, without affecting the control vector. There are two HhaI sites in the
      nuclear respiratory factor-1 (NRF-1) binding site of the Tfam promoter, whereas
      HpaII sites are present out of the NRF-1 region. It was concluded that the
      methylation on the NRF-1 sites might be a route for silencing Tfam promoter
      resulting in decrease of mitochondrial biogenesis.

PMID- 14715255
TI  - Insights into a conformational epitope of Hev b 6.02 (hevein).
AB  - Hevein (Hev b 6.02) is a major IgE-binding allergen in natural rubber latex and
      manufactured products. Both tryptophans (Trp(21) and Trp(23)) of the hevein
      molecule were chemically modified with BNPS-skatole (2-nitrophenylsulfenyl-3
      methyl-3(')-bromoindolenine); derivatized allergen failed to significantly
      inhibit binding of serum IgE in ELISA assays. Similarly, skin prick tests showed
      that hevein-positive patients gave no response with the modified allergen. Dot
      blot experiments carried out with anti-hevein mono- and polyclonal antibodies
      confirmed the importance of Trp(21) and Trp(23) for antibody-recognition, and
      demonstrated the specific cross-reactivity of other molecules containing hevein
      like domains. We also report the structure of Hev b 6.02 at an extended
      resolution (1.5A) and compare its surface properties around Trp residues with
      those of similar regions in other allergens. Overall our results indicate that
      the central part of the protein, which comprises three aromatic and other acidic
      and polar residues, constitutes a conformational epitope.

PMID- 14715256
TI  - Targeting of therapeutic gene expression to the liver by using liver-type
      pyruvate kinase proximal promoter and the SV40 viral enhancer active in multiple
      cell types.
AB  - To achieve the liver-directed expression in sufficient amounts of therapeutic
      genes for successful and safe gene therapy, natural liver-specific promoters can
      be used to direct the expression of therapeutic genes in the liver, whereas
      strong viral enhancers were used to obtain sufficient amounts of expressed
      therapeutic gene products. However, very often use of either the former or the
      latter does not guarantee both potent and liver-specific therapeutic gene
      expression. Here we conglomerate them and thus create a potent tissue-specific
      promoter by characterizing and using the liver-type pyruvate kinase proximal
      promoter (LPKPP) harboring its TATA box and a HNF-1alpha binding site. Alone it
      hardly activated its reporter gene expression in non-hepatocytes or hepatocytes.
      However, in the presence of the SV40 viral enhancer (SV40VE), which is active in
      multiple cell types, it was able to potently activate its reporter gene
      expression specifically in hepatocytes. The tissue-specific activation of the
      LPKPP by the viral enhancer was attributed to HNF-1alpha binding to the LPKPP.
      Taken together, these results support the idea that the constitutively active
      SV40VE could be used to activate the LPKPP in a tissue-specific manner in the
      presence of HNF-1alpha. To our knowledge, this is the first study to utilize HNF
      1alpha and its binding site, in the context of the LPKPP, to generate a basal
      promoter that is transcriptionally activated potently in a tissue-specific manner
      by a viral enhancer that is active in multiple cell types.

PMID- 14715257
TI  - 9-Hydroxystearic acid upregulates p21(WAF1) in HT29 cancer cells.
AB  - Growing evidence supports the critical role of lipid peroxidation products in the
      control of cell proliferation. In previous studies we demonstrated the efficient
      restriction of the proliferation rate in several cell lines resulting from the in
      vitro treatment with endogenous lipid polar components of cell membranes. Among
      these, 9-hydroxystearic acid (9-HSA), a primary intermediate of lipid
      peroxidation, induced a significant arrest in G0/G1 in HT29 colon cancer cells.
      In response to 9-HSA treatment of HT29 we observed cell growth arrest and
      increase in p21(WAF1) expression both at the transcriptional and the
      translational levels. Growth of p21(WAF1)-deleted HCT116 human colon carcinoma
      cells was not inhibited by 9-HSA. We present evidence that p21(WAF1) is required
      for 9-HSA mediated growth arrest in human colon carcinoma cells.

PMID- 14715258
TI  - Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells.
AB  - The constitutive activation of signal transducer and activator of transcription 3
      (Stat3) is frequently detected in breast carcinoma cell lines but not in normal
      breast epithelial cells. Stat3 has been classified as an oncogene because
      activated Stat3 can mediate oncogenic transformation in cultured cells and tumor
      formation in nude mice. In this study, we investigated potential Stat3 regulated
      genes in breast cells. Upon expression of Stat3-C, a constitutively active Stat3
      form, in nonmalignant telomerase immortalized breast cells (TERT), cell lysate
      was subjected to 2-dimensional (2-D) protein gel analysis. Our results showed
      that heat shock 27kDa protein (HSP27) was markedly induced by Stat3-C expression.
      Further analysis demonstrated that phosphorylation of HSP27 at serine residue 78
      was induced by Stat3-C in TERT breast cells as well as in MCF-10A and MDA-MB-453
      breast cells. RT-PCR result confirmed that HSP27 mRNA was induced by Stat3-C in
      TERT cells. As the result of Stat3 knock-down by Stat3 short interfering RNA
      oligonucleotides in MDA-MB-468 human breast carcinoma cells, HSP27 was markedly
      reduced consistent with Stat3 reduction. Furthermore, we observed that Stat3 was
      physically associated with HSP27 and HSP90 in MDA-MB-468 breast carcinoma cells.
      Taken together, our findings demonstrate that constitutively activated Stat3 up
      regulates HSP27 and may facilitate phosphorylation of HSP27 at serine residue 78.
      The up-regulation of HSP27 may be one of the underlying mechanisms with which
      aberrant Stat3 signaling induces cell malignancies.

PMID- 14715259
TI  - Expression of adiponectin receptors in human macrophages and regulation by
      agonists of the nuclear receptors PPARalpha, PPARgamma, and LXR.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors
      expressed in macrophages where they control cholesterol homeostasis and
      inflammation. In an attempt to identify new PPARalpha and PPARgamma target genes
      in macrophages, a DNA array-based global gene expression profiling experiment was
      performed on human primary macrophages treated with specific PPARalpha and
      PPARgamma agonists. Surprisingly, AdipoR2, one of the two recently identified
      receptors for adiponectin, an adipocyte-specific secreted hormone with anti
      diabetic and anti-atherogenic activities, was found to be induced by both
      PPARalpha and PPARgamma. AdipoR2 induction by PPARalpha and PPARgamma in primary
      and THP-1 macrophages was confirmed by Q-PCR analysis. Interestingly, treatment
      with a synthetic LXR agonist induced the expression of both AdipoR1 and AdipoR2.
      Furthermore, co-incubation with a PPARalpha ligand and adiponectin resulted in an
      additive effect on the reduction of macrophage cholesteryl ester content.
      Finally, AdipoR1 and AdipoR2 are both present in human atherosclerotic lesions.
      Moreover, AdipoR1 is more abundant than AdipoR2 in monocytes and its expression
      decreases upon differentiation into macrophages, whereas AdipoR2 remains
      constant. In conclusion, AdipoR1 and AdipoR2 are expressed in human
      atherosclerotic lesions and macrophages and can be modulated by PPAR and LXR
      ligands, thus identifying a mechanism of crosstalk between adiponectin and these
      nuclear receptor signaling pathways.

PMID- 14715260
TI  - Single-stranded DNA binding and methylation by EcoP1I DNA methyltransferase.
AB  - EcoP1I methyltransferase (M.EcoP1I) belongs to the type III restriction
      modification system encoded by prophage P1 that infects Escherichia coli. Binding
      of M.EcoP1I to double-stranded DNA and single-stranded DNA has been
      characterized. Binding to both single- and double-stranded DNA could be competed
      out by unlabeled single-stranded DNA. Metal ions did not influence DNA binding.
      Interestingly, M.EcoP1I was able to methylate single-stranded DNA. Kinetic
      parameters were determined for single- and double-stranded DNA methylation. This
      feature of the enzyme probably functions in protecting the phage genome from
      restriction by type III restriction enzymes and thus could be considered as an
      anti-restriction system. This study describing in vitro methylation of single
      stranded DNA by the type III methyltransferase EcoP1I allows understanding of the
      mechanism of action of these enzymes and also their role in the biology of single
      stranded phages.

PMID- 14715261
TI  - Intermediate formation at lower urea concentration in 'B' isomer of human serum
      albumin: a case study using domain specific ligands.
AB  - The urea-induced unfolding of 'N' isomer (occurring at pH 7.0) and 'B' isomer
      (occurring at pH 9.0) of human serum albumin was studied by fluorescence and
      circular dichroism spectroscopic measurements. Urea-induced destabilization in
      different domains of both the isomers was monitored by using domain specific
      ligands, hemin (domain-I), chloroform, bilirubin (domain-II), and diazepam
      (domain-III). Urea-induced denaturation of N and B isomers of HSA showed a two
      step, three-state transition with accumulation of intermediates around 4.8-5.2M
      and 3.0-3.4M urea concentrations, respectively. During first transition (0-4.8M
      urea for N isomer and 0-3.0M urea for B isomer) a continuous decrease in diazepam
      binding suggested major conformational changes in domain-III prior to
      intermediate formation. On the other hand, binding of hemin, a ligand for domain
      IB and chloroform, whose binding site is located in domain-IIA remains unchanged
      up to 5.0M urea for N isomer and 3.0M urea for B isomer. Similarly, fluorescence
      intensity of Trp-214 that resides in domain-IIA remained unchanged up to the
      above-said urea concentrations and decreased thereafter. Absence of any decrease
      in hemin binding, chloroform binding, and Trp-214 fluorescence suggested the non
      involvement of domain-IB and domain-IIA in intermediate formation. A significant
      increase in bilirubin binding prior to intermediate formation showed favorable
      conformational rearrangement in bilirubin binding cavity formed by loop 4 of
      domain-IB and loop 3 of domain-IIA. Further, a nearly complete abolishment of
      bilirubin binding to both isomers around 7.0M and 6.0M urea concentrations,
      respectively, indicated complete separation of domain-I from domain-II from each
      other. From these observations it can be concluded that N to B transition of
      human serum albumin shifted the intermediate formation towards lower urea
      concentration (3.0-3.4M urea for B isomer as against 4.8-5.2M urea for N isomer).
      Further both the intermediates were found to possess similar alpha-helical
      (approximately 39%) content and ligand binding properties.

PMID- 14715262
TI  - Stationary phase protein overproduction is a fundamental capability of
      Escherichia coli.
AB  - Although Escherichia coli is well studied and various recombinant E. coli protein
      expression systems have been developed, people usually consider the rapid growing
      (log phase) culture of E. coli as optimum for production of proteins. However,
      here we demonstrate that at stationary phase three E. coli systems, BL21
      (DE3)(pET), DH5alpha (pGEX) induced with lactose, and TG1 (pBV220) induced with
      heat shock could overexpress diversified genes, including three whose products
      are deleterious to the host cells, more stably and profitably than following the
      log phase induction protocol. Physical and patch-clamp assays indicated that
      characteristics of target proteins prepared from cultures of the two different
      growth phases coincide. These results not only provide a better strategy for
      recombinant protein preparation in E. coli, but also reveal that rapid
      rehabilitation from stresses and stationary phase protein overproduction are
      fundamental characters of E. coli.

PMID- 14715263
TI  - Surface activity and interaction of StarD7 with phospholipid monolayers.
AB  - StarD7 protein forms stable Gibbs and Langmuir monolayers at the air-buffer
      interface showing marked surface activity. The latter is enhanced by penetration
      into phospholipid films at an initial surface pressure above the protein's own
      equilibrium adsorption surface pressure to a lipid-free interface. The protein
      phospholipid stabilizing interactions at the interface depend on the lipid, with
      preference for phosphatidylserine, cholesterol, and phosphatidylglycerol, and the
      increases of lateral surface pressure generated are comparable to those of other
      membrane-active proteins. The surface activity of StarD7 is strong enough to
      thermodynamically drive and retain StarD7 at the lipid membrane interface where
      it may undergo lipid-dependent reorganization as indicated by changes of surface
      pressure and electrostatics.

PMID- 14715264
TI  - Sensitization of mesothelioma to TRAIL apoptosis by inhibition of histone
      deacetylase: role of Bcl-xL down-regulation.
AB  - The TNF-related apoptosis-inducing ligand (TRAIL) is an immunological inducer of
      apoptosis selectively killing many, but not all, cancer cells. Malignant
      mesothelioma (MM) is fatal neoplasia with no current treatment, most likely due
      to high resistance of MM cells towards inducers of apoptosis, including TRAIL. We
      studied whether inhibition of histone deacetylase (HDAC), recently shown to
      sensitize malignant cells to a variety of apoptogenic substances, renders MM
      cells susceptible to TRAIL. Indeed, sub-apoptotic doses of the HDAC inhibitor
      suberohydroxamic acid (SBHA) sensitized MM cells to TRAIL apoptosis. Of the
      apoptotic mediators tested, the anti-apoptotic protein Bcl-x(L) was strongly down
      regulated by combined treatment of the cells with SBHA and TRAIL but not by the
      HDAC inhibitor alone, while little or no change in the expression of other Bcl-2
      family members highly expressed in MM cells, including Mcl-1 and Bax, was
      observed. Our data suggest a cross-talk between HDAC inhibition and TRAIL that
      results in modulation of expression of specific apoptotic mediators, and point to
      the potential of their combinatorial use in treatment of TRAIL-resistant
      neoplastic disease.

PMID- 14715265
TI  - A structure-activity relationship study on N-arachidonoyl-amino acids as possible
      endogenous inhibitors of fatty acid amide hydrolase.
AB  - N-arachidonoyl-glycine (NAGly) has been recently identified in rodent tissues and
      found to exhibit analgesic activity in vivo. NAGly is a potent inhibitor of the
      fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for the
      degradation of the endocannabinoid N-arachidonoyl-ethanolamine (anandamide), and
      was shown recently to elevate the blood levels of the this analgesic compound. We
      have synthesized several N-arachidonoyl-amino acids of potential natural
      occurrence, as well as the D- and L-isomers of N-arachidonoyl-alanine, and have
      tested their activity on FAAH preparations from mouse, rat, and human cell lines,
      and from mouse or rat brain. The results indicate that the relative potency and
      enantioselectivity of N-arachidonoyl-amino acids as FAAH inhibitors depend on the
      animal species. Thus, whilst NAGly is the most potent compound on the rat and
      mouse enzymes, N-arachidonoyl-isoleucine is active only on human FAAH and N
      arachidonoyl-alanine enantiomers show a varying degree of potency. Taken
      together, these data support the view that an enhancement of endogenous
      anandamide levels underlies in part the analgesic effects of NAGly in rodents.

PMID- 14715266
TI  - Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and
      NF-kappaB.
AB  - Signaling pathways involved in oxidative stress-induced inhibition of osteoblast
      differentiation are not known. We showed in this report that H(2)O(2) (0.1-0.2mM)
      induced oxidative stress suppressed the osteoblastic differentiation process of
      primary rabbit bone marrow stromal cells (BMSC) and calvarial osteoblasts,
      manifested by a reduction of differentiation markers including alkaline
      phosphatase (ALP), type I collagen, colony-forming unit-osteoprogenitor (CFU-O)
      formation, and nuclear phosphorylation of Runx2. H(2)O(2) treatment stimulated
      phospholipase C-gamma1 (PLC-gamma1), extracellular signal-regulated kinase 1/2
      (ERK1/2), and NF-kappaB signaling but inhibited p38 mitogen-activated protein
      kinase (MAPK) activation. In the presence of 20microM PD98059 or 50microM caffeic
      acid phenethyl ester (CAPE), specific inhibitor for ERKs or NF-kappaB,
      respectively, could significantly reverse the decrease of above-mentioned
      osteoblastic differentiation markers elicited by H(2)O(2) (0.1mM). Furthermore,
      PD98059 also suppressed H(2)O(2)-stimulated NF-kappaB signaling in this process.
      These data suggest that ERK and ERK-dependent NF-kappaB activation is required
      for oxidative stress-induced inhibition of osteoblastic differentiation in rabbit
      BMSC and calvarial osteoblasts.

PMID- 14715267
TI  - Molecular dissection of mouse soluble guanylyl cyclase alpha1 promoter.
AB  - Soluble guanylyl cyclase (sGC) is the only known receptor for nitric oxide (NO)
      and is downregulated in aging and hypertension. Little is known about sGC gene
      transcriptional regulation. In order to characterize the sGC transcriptional
      system, we cloned and sequenced the 5(') flanking region of mouse sGC alpha(1)
      gene (AY116663). Structurally, it is a non-canonical TATA-less promoter that we
      mapped to chromosome 3 with many putative regulation sites for Sp-1, NF-kappaB,
      and AP-1 transcription factors amongst others, and two (TG:CA)(n) dinucleotide
      microsatellites near the transcriptional start point. The cloned upstream
      sequence produced a 5-fold increase in luciferase activity in Cos7, HeLa, NIH3T3,
      and 293 cells as well as in mouse VSMC-like kidney mesangial cells. In the latter
      cell type, we showed that sGC alpha(1) promoter activity was dependent on the
      presence of its 5(') unstranslated region (5(')UTR).

PMID- 14715268
TI  - Egg capsule secretion in invertebrates: a new ovarian regulatory peptide
      identified by mass spectrometry comparative screening in Sepia officinalis.
AB  - Mass spectrometry comparative screening was used to identify ovarian regulatory
      peptides involved in the successive steps of egg-laying in the cuttlefish Sepia
      officinalis. The peptide content of full-grown oocytes (FGO) was compared with
      that of oocyte-conditioned medium, which resulted in the detection of peptides
      that were present in both samples. These peptides, which are suspected of being
      released by the oocyte in the genital tract, were submitted to a structural
      analysis. This strategy led to the characterization of a new ovarian regulatory
      peptide (EISLDKD) able to inhibit the contractions of the whole female genital
      tract and of the main nidamental glands (MNG). As EISLDKD appeared to be the
      first regulatory peptide directly involved, at physiological concentrations, in
      the secretion of the egg capsule by the main nidamental glands, it was named
      SepCRP for Sepia Capsule Releasing Peptide. Mass spectrometry analysis clearly
      demonstrated that SepCRP was expressed during vitellogenesis by the ovarian
      follicles and released by the FGO in the lumen of the female genital tract. In
      association with the ovarian 5-HT, SepCRP would be responsible for the storage of
      FGO to avoid the spawning of unfertilized oocytes before mating. Released by the
      distal oviduct in the mantle cavity, SepCRP probably in association with a
      cocktail of ovarian regulatory factors targets the MNG to regulate the egg
      capsule secretion. Thus, the ovary appeared to be one of the main sources of
      regulatory peptides involved in the successive steps of egg-laying in the
      cephalopod mollusk S. officinalis.

PMID- 14715269
TI  - Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated
      with lung cancer.
AB  - RUNX family transcription factors are integral components of TGF-beta signaling
      pathways and have been implicated in cell cycle regulation, differentiation,
      apoptosis, and malignant transformation. It was noted previously that allele loss
      and loss of expression of RUNX3 are causally involved in gastric carcinogenesis.
      Our results demonstrate that RUNX3 is inactivated by aberrant DNA methylation in
      approximately 19% of lung cancer cell lines and 24% of primary lung cancer
      specimens. RUNX3 methylation is tumor-specific, since it is not observed in
      surrounding normal lung tissues. Our results suggest that loss of RUNX3
      expression by DNA hypermethylation is frequently associated with the evolution of
      lung cancer.

PMID- 14715270
TI  - Biophysical characterization of Gir2, a highly acidic protein of Saccharomyces
      cerevisiae with anomalous electrophoretic behavior.
AB  - Gir2 is an uncharacterized protein of Saccharomyces cerevisiae, containing a
      RWD/GI domain. In this work, we report the biophysical characterization of Gir2.
      His-tagged Gir2, expressed and purified from Escherichia coli, showed an
      abnormally slow migration on SDS-PAGE. The yeast expressed protein behaves
      similarly. Using mass spectrometry and peptide mass fingerprinting we
      demonstrated that the protein has the expected molecular mass (34kDa). EDC
      modification of carboxylate groups reverted the anomalous migration on SDS-PAGE.
      Size exclusion chromatography showed that Gir2 has a Stokes radius larger than
      expected. Gir2 is thermostable and lacks extensive structure, as determined by CD
      analysis. Based on these findings, we suggest that Gir2 is a representative of
      the growing group of "natively unfolded" proteins.

PMID- 14715271
TI  - A model of the ACE2 structure and function as a SARS-CoV receptor.
AB  - The angiotensin-converting enzyme 2 (ACE2) is an important regulator of the renin
      angiotensin system and was very recently identified as a functional receptor for
      the SARS virus. The ACE2 sequence is similar (sequence identities 43% and 35%,
      and similarities 61% and 55%, respectively) to those of the testis-specific form
      of ACE (tACE) and the Drosophila homolog of ACE (AnCE). The high level of
      sequence similarity allowed us to build a robust homology model of the ACE2
      structure with a root-mean-square deviation from the aligned crystal structures
      of tACE and AnCE less than 0.5A. A prominent feature of the model is a deep
      channel on the top of the molecule that contains the catalytic site. Negatively
      charged ridges surrounding the channel may provide a possible binding site for
      the positively charged receptor-binding domain (RBD) of the S-glycoprotein, which
      we recently identified [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Several
      distinct patches of hydrophobic residues at the ACE2 surface were noted at close
      proximity to the charged ridges that could contribute to binding. These results
      suggest a possible binding region for the SARS-CoV S-glycoprotein on ACE2 and
      could help in the design of experiments to further elucidate the structure and
      function of ACE2.

PMID- 14715272
TI  - Characterization of a novel member of murine semaphorin family.
AB  - Semaphorin gene family contains a large number of secreted and transmembrane
      proteins, and some of them are functioning as the repulsive and attractive cues
      of the axon guidance during development. Here we report murine orthologues of a
      novel member of class 6 semaphorin gene, semaphorin 6D (Sema6D), mapped on the
      chromosome 2. Sema6D is mainly expressed in the brain and lung, and the
      ubiquitous expression in the brain continues from embryonic late stage to
      adulthood, as determined by Northern blot and in situ hybridization. We also
      found that Sema6D has five different splicing variants, and the expression
      patterns of individual isoforms differ depending on the tissues. Thus, Sema6D may
      play important roles in various functions including the axon guidance during
      development and neuronal plasticity.

PMID- 14715273
TI  - Identification of 5'-upstream region of pufferfish ribosomal protein L29 gene as
      a strong constitutive promoter to drive GFP expression in zebrafish.
AB  - The genomic structure of Tetraodon fluviatilis L29 gene was determined and its
      promoter activity was analyzed in COS-1 cells and zebrafish embryos. The TfL29
      gene comprises four exons and three introns, spanning approximately 1.7kb. The
      5(')-upstream 2.2-kb of the first exon contains 10 E-boxes and many putative
      binding motifs for transcription factors GATA-1, AML-1a, c-Myb, Oct-1, CdxA, and
      NRF-2. Promoter activity assay showed that the distal 2.2-kb fragment not only
      had high luciferase activity in COS-1 cells, but also strong and ubiquitous GFP
      expression in a variety of tissues in zebrafish embryos. On the other hand, there
      are no TATA or CAAT boxes within a 300-bp region upstream from the transcription
      initiation site. Although this region has high luciferase activity in COS-1
      cells, it is not sufficient to drive GFP expression in zebrafish embryos. In this
      proximal 300-bp region, there are two E-boxes, two CdxA sites, and one NRF-2 site
      that is immediately downstream of the transcription start site.

PMID- 14715274
TI  - A two-component signal transduction system with a PAS domain-containing sensor is
      required for virulence of Mycobacterium tuberculosis in mice.
AB  - Mycobacterium tuberculosis, the causative organism of tuberculosis, encounters
      oxidative stress during phagocytosis by the macrophage and following macrophage
      activation during an acquired immune response, and also from internally generated
      sources of radical oxygen intermediates through intermediary metabolism. We have
      identified the SenX3 protein, a sensor in 1 of the 11 complete pairs of two
      component signal transduction systems in M. tuberculosis, as a possible
      orthologue of the Mak2p protein from the fission yeast Schizosaccharomyces pombe
      that is known to sense peroxide stress. Moreover, the SenX3-RegX3 two-component
      system was the top scoring hit in a homology search with the Escherichia coli
      ArcB-ArcA global control system of aerobic genes. Using structural modelling
      techniques we have determined that SenX3 contains a PAS-like domain found in a
      variety of prokaryotic and eukaryotic sensors of oxygen and redox. Mutants with
      knock-outs of senX3 or of the accompanying transcriptional regulator regX3 were
      constructed and found to have reduced virulence in a mouse model of tuberculosis
      infection, the mutant bacteria persisting for up to 4 months post-infection;
      complemented mutants had regained virulence confirming that it was mutations of
      this two-component system that were responsible for the avirulent phenotype. This
      work identifies the PAS domain as a possible drug target for tuberculosis and
      mutations in the senX3-regX signal transduction system as potentially useful
      components of live vaccine strains.

PMID- 14715275
TI  - Rpp20 interacts with SMN and is re-distributed into SMN granules in response to
      stress.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disorder resulting from
      homozygous loss of the SMN1 gene. To investigate SMN functions, we undertook the
      yeast two-hybrid screens and identified Drosophila Rpp20, a subunit of the RNase
      P and RNase MRP holoenzymes, to interact with the Drosophila SMN protein.
      Interaction between human SMN and Rpp20 was validated by in vitro binding assays
      and co-immunoprecipitation. The exons 3-4 of SMN are necessary and sufficient for
      binding to Rpp20. Binding efficiency between Rpp20 and SMNs with mutations in the
      Y-G domain is abrogated or reduced and correlated with severity of SMA disease.
      Immunofluorescence results indicate that Rpp20 is diffusely distributed
      throughout the cytoplasm with higher concentration observed in the nucleus.
      However, in response to stress, SMN forms aggregates and redistributes Rpp20 into
      punctuated cytoplasmic SMN granules. Our findings suggest a possible functional
      association of SMN with RNase P and RNase MRP complexes.

PMID- 14715276
TI  - Heparin affin regulatory peptide in milk: its involvement in mammary gland
      homeostasis.
AB  - HARP (heparin affin regulatory peptide) is a heparin binding growth factor
      implicated in cellular growth and differentiation. Previously, HARP had been
      localized in the human mammary, in both alveolar epithelial and myoepithelial
      cells although HARP mRNAs were only expressed by myoepithelial cells [J.
      Histochem. Cytochem. 45 (1997) 1]. In the present study, we demonstrate that HARP
      is secreted in human mature milk with concentrations ranging from 17.68+/
      6.4ng/ml in mature milk to 59.9+/-11.22ng/ml in colostrum. In vitro, HARP was
      found to be mitogenic on human mammary epithelial and myoepithelial cell lines
      and correlated with the expression of its high affinity receptor tyrosine kinase
      ALK (anaplastic lymphoma kinase). In vivo, ALK is expressed in both mammary
      epithelial and myoepithelial cells, suggesting that HARP could act in vivo as a
      paracrine and autocrine growth factor in the regulation of the mammary gland
      development and its homeostatic maintenance during pregnancy and lactation.

PMID- 14715277
TI  - siRNA-based inhibition specific for mutant SOD1 with single nucleotide
      alternation in familial ALS, compared with ribozyme and DNA enzyme.
AB  - In many of autosomal dominant diseases such as familial amyotrophic lateral
      sclerosis (ALS) with SOD1 mutation, a missense point mutation may induce the
      disease by its gain of adverse property. Reduction of such a mutant protein
      expression is expected to improve the disease phenotype. Duplex of 21-nt RNA,
      known as siRNA, has recently emerged as a powerful tool to silence gene, but the
      sequence specificity and efficacies have not been fully studied in comparison
      with ribozyme and DNA enzyme. We could make the siRNA which recognized even a
      single nucleotide alternation and selectively suppress G93A SOD1 expression
      leaving wild-type SOD1 intact. In mammalian cells, the siRNA much more
      efficiently suppressed the expression of mutant SOD1 than ribozyme or DNA enzyme.
      Furthermore, these siRNAs could suppress cell death of Neuro2a induced by over
      expression of mutant SOD1s with stress of proteasome inhibition. Our results
      support the feasibility of utilizing siRNA-based gene therapy of familial ALS
      with mutant SOD1.

PMID- 14715278
TI  - HuBMSC-MCP, a novel member of mitochondrial carrier superfamily, enhances
      dendritic cell endocytosis.
AB  - A novel member of mitochondrial carrier superfamily has been identified from
      human bone marrow stromal cells (BMSC) and designated as human BMSC-derived
      mitochondrial carrier protein (HuBMSC-MCP). It encodes a 321 amino-acid protein
      with three tandem related domains of about 100 amino acids. Each domain contains
      two hydrophobic stretches, which are thought to span the membrane as alpha
      helices. Distant relationship analysis indicates that the protein is highly
      conserved between species from Caenorhabditis elegans to human. HuBMSC-MCP gene
      is mapped to chromosome 11p11. HuBMSC-MCP mRNA expression is detectable in
      various human tissues and cell lines. By confocal imaging, HuBMSC-MCP is
      localized to mitochondria and also detected in the pseudopodial protrusion of
      human breast adenocarcinoma MCF-7 cells. When transfected into dendritic cells
      (DC), HuBMSC-MCP could enhance DCs endocytotic capacity. Thus, HuBMSC-MCP is a
      phylogenetically conserved and widely expressed mitochondrial carrier protein
      which perhaps associates with mitochondrial oxidative phosphorylation.

PMID- 14715279
TI  - Determination of the net charge (valence) of a protein: a fundamental but elusive
      parameter.

PMID- 14715280
TI  - Preparation and utilization of a reagent for the isolation and purification of
      low-molecular-mass thiols.
AB  - Problems inherent in the isolation of thiols from natural sources, such as
      oxidation, undesirable addition reactions, and low concentration of thiol species
      in cell-free extracts, can be circumvented by reversible derivatization to a less
      labile form which can be concentrated selectively. These objectives are realized
      by converting thiols to heterodisulfides in which the thiol partner is an apolar
      thiol with strong affinity for hydrophobic stationary phases. When reacted with 2
      S-(2(')-thiopyridyl)-6-hydroxynaphthyldisulfide at pH<5, where most thiol species
      are relatively stable to atmospheric oxidation, mixed disulfides with 2-mercapto
      6-hydroxynaphthalene as the apolar partner are obtained in good yield and can be
      concentrated onto a hydrophobic stationary phase. Such heterodisulfides exhibit
      excellent chromatographic properties when separated on reversed-phase media and
      the derivatization reaction can, therefore, be conveniently monitored. Following
      their isolation as the heterodisulfides the thiol species of interest are
      recovered by reduction and facile separation from the apolar 2-mercapto-6
      hydroxynaphthalene partner.

PMID- 14715281
TI  - Halide fluxes in epithelial cells measured with an automated cell plate reader.
AB  - A method is introduced to measure chloride permeability in cultured epithelial
      cells using 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 6-methoxy-N
      ethylquinolinium iodide quinolinium (MEQ) as fluorescent chloride-sensitive
      probes. The method involves growing cells in multiwell plates, incubating cells
      with SPQ or MEQ, and then exchanging intracellular or extracellular halide ions
      with nitrate. The resulting time course of SPQ or MEQ fluorescence is followed by
      repetitive readings with a multiwell fluorescence plate reader. Exchange times
      are extracted by fitting the time course with a single exponential function of
      time. The method was validated by measuring the effect of chloride channel
      activators and blockers in A6 and MDCK cells. The baseline iodide/nitrate
      exchange time was 200-300 s. Isoproterenol (a modulator of cAMP-activated
      chloride channels) increased the exchange rate by a factor of 1.4+/-0.1; A23187
      (a modulator of calcium-activated chloride channels) increased the rate by 3.4+/
      0.4; bradykinin (also a modulator of calcium-activated chloride channels)
      increased the rate by 2.0+/-0.4; forskolin (a direct stimulator of adenylate
      cyclase) increased the rate by 2.7+/-0.3. Diphenylamine-2-carboxylate (a chloride
      channel blocker) decreased the rate by 0.12+/-0.03. These results indicate that
      our method is a valid indicator of halide-nitrate exchange in cultured epithelial
      cells.

PMID- 14715282
TI  - A glycomic approach to proteoglycan with a two-dimensional polysaccharide chain
      map.
AB  - Glycosaminoglycan chains were liberated from proteoglycans (bovine lung, tracheal
      cartilage, and cerebrum) by successive digestion with actinase and with cellulase
      from Aspergillus niger, which has endo-beta-xylosidase activity. The
      glycosaminoglycan chains were fluorescence-labeled with 2-aminopyridine after
      digestion with Streptomyces hyaluronidase. The resulting pyridylamino
      glycosaminoglycans, including heparan sulfate, chondroitin sulfate/dermatan
      sulfate, and heparin, were separated by high-performance liquid chromatography.
      Each separated fraction was analyzed by two types of high-performance liquid
      chromatography: gel-filtration chromatography and anion-exchange chromatography.
      The correlation between molecular weight and degree of sulfation could be shown
      on the two-dimensional polysaccharide chain map. Use of a commonly available
      cellulase with endo-beta-xylosidase activity together with the two-dimensional
      polysaccharide chain map allows easy analysis of various glycosaminoglycan chains
      and comprehensive comparison among the structures. These techniques will become
      useful tools in the further development of glycotechnology and glycome analysis.

PMID- 14715283
TI  - Solid-phase extraction-electrospray ionization mass spectrometry for the
      quantification of folate in human plasma or serum.
AB  - The measurement of 5-methyltetrahydrofolic acid (5 MT) blood levels is one of
      several factors used to diagnose folate deficiency in humans. 5 can be
      selectively purified from either human plasma or human serum via solid-phase
      extraction procedures and specifically detected and quantified in the extracts
      with liquid chromatography/isotope-dilution electrospray-ionization mass
      spectrometry. Two different, yet complementary, solid-phase extraction-liquid
      chromatography/mass spectrometry methods have been developed and applied to the
      quantification of 5 MT from such extracts. One method utilizes the high-affinity
      folate-binding protein from cow's milk coupled with multiple-reaction-monitoring
      mode tandem mass spectrometry while the other method utilizes reversed-phase
      C(18) extraction followed by selected-ion-monitoring-mode mass spectrometry. The
      accuracy of each method is assessed through a comparative determination of 5 MT
      levels in homogenous plasma and serum pools. Additionally, each method is
      compared and evaluated against the "total folate" results provided by routine
      radioassay and microbiological assay determinations. On the basis of the
      experimental data presented in this report, it is suggested that both methods
      have the capacity to serve as potential reference methods for the quantification
      of circulating 5MT in plasma or serum.

PMID- 14715284
TI  - Use of a novel double-sandwich enzyme-linked immunosorbent assay method for
      assaying chondroitin sulfate proteoglycans that bear 3-nitrotyrosine core protein
      modifications, a previously unrecognized proteoglycan modification in
      hydrocephalus.
AB  - 3-Nitrotyrosine is a useful marker for nitric oxide-mediated tissue injury.
      However, which proteins are preferred peroxynitrite modification targets is
      unclear. Chondroitin sulfate proteoglycans (CSPGs) abnormally accumulate in
      cerebrospinal fluid of human neonates with hydrocephalus and may be a target for
      peroxynitrite modification. We examined (1). whether CSPG core protein can be
      modified by peroxynitrite in vitro; (2). to what degree in comparison to bovine
      serum albumin (BSA), the most commonly used nitrated protein standard; (3).
      whether nitrated CSPGs can be measured directly in biological samples; and (4).
      whether nitrated proteoglycan concentrations in cerebrospinal fluid correlate
      with disease. In vitro nitration of bovine aggrecan was performed by exposure to
      different peroxynitrite concentrations, and 3-nitrotyrosine products were
      measured. Bovine serum albumin (BSA) nitration was also performed in comparison.
      A larger percentage of tyrosine residues were nitrated in aggrecan than in BSA
      under all conditions tested. An enzyme-linked immunosorbent assay (ELISA) for 3
      nitrotyrosine consistently overestimated aggrecan nitration when nitrated BSA was
      used as the standard. This is important as most current assays of nitration in
      biological samples use nitrated BSA as the standard. Therefore, if nitrated CPSGs
      were a substantial portion of the nitrated proteins in a sample, total nitrated
      protein content would be overestimated. Aggrecan retained its function of binding
      hyaluronic acid despite substantial nitration. A double-sandwich ELISA was
      developed for nitrated CSPGs in biological samples, using nitrated aggrecan as
      standard. [Nitrated CSPG] was found to be significantly elevated in preterm
      hydrocephalus cerebrospinal fluid (P<0.02), but correlated poorly with
      cerebrospinal fluid [nitric oxide] (P>0.069), suggesting that nitrated CSPG and
      NO levels may be independant markers of tissue injury. Peroxynitrite-mediated
      protein tyrosine nitration is a previously unrecognized modification of CSPGs,
      and may reflect level of brain injury in hydrocephalus.

PMID- 14715285
TI  - Synthesis and utility of 14C-labeled nicotinamide cofactors.
AB  - A new method for the synthesis of the reduced form of beta-nicotinamide [U
      14C]adenine dinucleotide 2(')-phosphate([Ad-14C]NADPH) is presented. The present
      synthesis results in a radioactive material with a specific activity that is
      greater than 220 mCi/mmol. This method could easily be adapted for syntheses of
      14C-labeled NADH, NADP(+), or any nicotinamide cofactors with radiolabels in
      other positions. Since these cofactors are so ubiquitous, the use and
      applications of such labeled material has broad implications. The utility of the
      labeled cofactor for determination of substrates for nicotinamide-dependent
      enzymes in the nano- to femtomole scale, in alternative enzymatic assays, and in
      kinetic isotope effect studies is discussed.

PMID- 14715286
TI  - Use of protein biotinylation in vivo for chromatin immunoprecipitation.
AB  - We describe a system designed to express biotinylated proteins in mammalian cells
      in vivo and its application to the study of protein-DNA interactions in vivo by
      chromatin immunoprecipitation (ChIP). The system is based on coexpression of the
      target protein fused to a short biotin acceptor domain together with the
      biotinylating enzyme BirA from Escherichia coli. The superior strength of the
      biotin-avidin interaction allows one to employ more stringent washing conditions
      in the ChIP protocol, resulting in a better signal/noise ratio.

PMID- 14715287
TI  - Determination of adenosine nucleotides in cultured cells by ion-pairing liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - A method using ion-pairing liquid chromatography-mass spectrometry (MS) was
      developed for analyzing adenosine 5(')-monophosphate (AMP), adenosine 5(')
      diphosphate (ADP), and adenosine 5(')-triphosphate (ATP) in cellular extracts.
      Dimethylhexylamine (DMHA) was used as ion-pairing agent to retain and separate
      the analytes on a reversed-phase microbore column with a gradient program.
      Positive-ion electrospray ionization-MS was applied for the detection because of
      the use of the ion-pairing agent. Adduct ions of DMHA with AMP, ADP, and ATP were
      found to be the most intensive peaks and thus selected as quantitative ions. An
      external calibration method with linear ranges from 0.1 to 20 microM for AMP, 2
      to 20 microM for ADP, and 2.5 to 20 microM for ATP was used for the quantitation.
      The method was applied to determine concentrations of AMP, ADP, and ATP in
      extracts of cultured rat C6 glioma cells that were pretreated with various
      concentrations of Zn. The detected levels of the adenosine nucleotides have been
      used to calculate total adenosine nucleotide and energy charge potential. Changes
      in cellular energy status upon exposure to increasing concentration of Zn in the
      culture medium were analyzed. The results indicated that the addition of Zn in a
      range of 40 to 120 microg/ml cause a gradual increased in energy charge potential
      of the cells.

PMID- 14715288
TI  - Spectrophotometric determination of de novo hemozoin/beta-hematin formation in an
      in vitro assay.
AB  - Formation of hemozoin in the malaria parasite, due to its unique nature, is an
      attractive molecular target. Several laboratories have been trying to unravel the
      molecular mechanism of hemozoin biosynthesis within the parasite digestive
      vacuoles. Use of different assay protocols for in vitro beta-hematin (synthetic
      identical to hemozoin) formation by these laboratories has led to inconsistent
      and often contradictory findings. Much of the difficulty may be attributed to
      oligomeric heme aggregates, which may be indistinguishable in some detection
      approaches if adequate separation of beta-hemtin is not achieved. Therefore,
      there is an urgent need for a widely accepted protocol for in vitro beta-hematin
      formation. We describe here a spectrophotometric assay for in vitro beta-hematin
      formation. The assay has been validated with the Plasmodium falciparum lysate,
      the parasite lipid extracts, and some commercially available fatty acids, which
      are known to initiate/catalyze beta-hematin formation in vitro. The necessity for
      multiple wash steps for accurate quantification of de novo hemozoin/beta-hematin
      formation was verified experimentally. It was necessary to wash the pellet, which
      contains beta-hematin and heme aggregates, sequentially with Tris/SDS buffer and
      alkaline bicarbonate solution for complete removal of monomeric heme and heme
      aggregates and accurate quantification of beta-hematin formed during the assay.
      The pellets and side products in the supernatant were characterized by infrared
      spectroscopy. No beta-hematin formation occurred in the absence of a
      catalytic/initiating factor. Based on these findings, a filtration-based assay
      that uses 96-well microplates, and which has important application in in vitro
      screening and identification of novel inhibitors of hemozoin formation as
      potential blood schizontocidal antimalarials, has been developed.

PMID- 14715289
TI  - Hydrogel drop microchips with immobilized DNA: properties and methods for large
      scale production.
AB  - Although gel-based microchips offer significant advantages over two-dimensional
      arrays, their use has been impeded by the lack of an efficient manufacturing
      procedure. Here we describe two simple, fast, and reproducible methods of
      fabrication of DNA gel drop microchips. In the first, copolymerization method,
      unsaturated groups are chemically attached to immobilized molecules, which are
      then mixed with gel-forming monomers. In the second, simpler polymerization
      mediated immobilization method, aminated DNA without prior modification is added
      to a polymerization mixture. Droplets of polymerization mixtures are spotted by a
      robot onto glass slides and the slides are illuminated with UV light to induce
      copolymerization of DNA with gel-forming monomers. This results in immobilization
      of DNA within the whole volume of semispherical gel drops. The first method can
      be better controlled while the second one is less expensive, faster, and better
      suited to large-scale production. The microchips manufactured by both methods are
      similar in properties. Gel elements of the chip are porous enough to allow
      penetration of DNA up to 500 nucleotides long and its hybridization with
      immobilized oligonucleotides. As shown with confocal microscope studies, DNA is
      hybridized uniformly in the whole volume of gel drops. The gels are mechanically
      and thermally stable and withstand 20 subsequent hybridizations or 30-40 PCR
      cycles without decrease in hybridization signal. A method for quality control of
      the chips by staining with fluorescence dye is proposed. Applications of hydrogel
      microchips in research and clinical diagnostics are summarized.

PMID- 14715290
TI  - Preparation and mass spectrometry of 14 pure and 18O(2)-labeled oxidation
      products from the phytosterols beta-sitosterol and stigmasterol.
AB  - To lower cholesterol, phytosterols are currently introduced as food additives,
      where they may become oxidized. In addition, specific biological effects of
      oxyphytosterols are suggested by the recent molecular clarification of the
      phytosterol storage disease as a dysfunctional mutation of an active sterol
      reexporter potentially regulated by oxidized phytosterols. We therefore studied
      the hydroxybenzotriazole-mediated PbO(2)-driven oxidation of phytosterols and
      compared it to the oxidation of cholesterol. We prepared, identified, and
      purified standards of 14 oxidation products of two major phytosterols. The gas
      chromatographic mass spectrometric characteristics of the 7alpha- and 7beta
      hydroxy-, 5alpha,6alpha-epoxy, 5beta,6beta-epoxy, 7keto-, 3beta,5alpha,6beta
      trihydroxy-, 3keto-, and 7-dehydro-derivatives of beta-sitosterol and
      stigmasterol are presented. The method also provided a convenient access to
      prepare 18O-labeled oxyphytosterols of high chemical and isotopic purity and can
      easily be extended to further phytosterols and -stanols. This enables the gas
      chromatography-mass spectrometry analysis of oxyphytosterols and the study of
      their biological effects.

PMID- 14715291
TI  - Formation of tannin-albumin nano-particles at neutral pH as measured by light
      scattering techniques.
AB  - Aggregation phenomena of tannin with bovine serum albumin were investigated by
      light scattering techniques including photon correlation spectroscopy and
      Rayleigh scattering. Tannin and albumin formed particles with diameters less than
      1 microm at neutral pH. As revealed by this study, light scattering methods are
      useful in investigating aggregation phenomena of biomolecules and in directly
      quantifying tannin content.

PMID- 14715292
TI  - Solubilization of membrane proteins for two-dimensional gel electrophoresis:
      identification of sarcoplasmic reticulum membrane proteins.
AB  - Solubilization of membrane proteins for two-dimensional electrophoresis (2DE) is
      very difficult. In this study, we report the use of 1,2-diheptanoyl-sn-glycero-3
      phosphatdiyl choline (DHPC) as a detergent to solubilize integral membrane
      proteins for 2DE. Rat ventricular microsomal fractions enriched with
      sarco(endo)plasmic reticulum (SR) membrane proteins were used as a model system.
      Compatibility of DHPC with a high concentration of urea increases the solubility
      of proteins compared with sulphobetaines or ASB-14. Peptide mass analysis
      assisted in the identification of key SR membrane proteins including SR Ca(2+)
      ATPase and other membrane proteins, which have not previously been reported on
      2DE. These results suggest that DHPC is a better detergent for solubilizing
      membrane proteins and may be useful in generating proteomic maps for most complex
      organelles including SR.

PMID- 14715293
TI  - A Biacore biosensor method for detailed kinetic binding analysis of small
      molecule inhibitors of p38alpha mitogen-activated protein kinase.
AB  - Protein kinases are emerging as one of the most intensely studied classes of
      enzymes as their central roles in physiologically and clinically important
      cellular signaling events become more clearly understood. We report here the
      development of a real-time, label-free method to study protein kinase inhibitor
      binding kinetics using surface plasmon resonance-based biomolecular interaction
      analysis (Biacore). Utilizing p38alpha mitogen-activated protein kinase as a
      model system, we studied the binding properties of two known small molecule
      p38alpha inhibitors (SB-203580 and SKF-86002). Direct coupling of p38alpha to the
      biosensor surface in the presence of a reversible structure-stabilizing ligand
      (SB-203580) consistently produced greater than 90% active protein on the
      biosensor surface. The dissociation and kinetic constants derived using this
      Biacore method are in excellent agreement with values determined by other
      methods. Additionally, we extend the method to study the thermodynamics of small
      molecule binding to p38alpha and derive a detailed thermodynamic reaction pathway
      for SB-203580. The Biacore method reported here provides an efficient way to
      directly and reproducibly examine dissociation constants, kinetics, and
      thermodynamics for small molecules binding to p38alpha and possibly other protein
      kinases. Immobilization in the presence of a stabilizing ligand may further
      represent a broadly applicable paradigm for creation of highly active biosensor
      surfaces.

PMID- 14715294
TI  - Tris(2-carboxyethyl)phosphine stabilization of RNA: comparison with
      dithiothreitol for use with nucleic acid and thiophosphoryl chemistry.
AB  - We assessed the utility of the sulfhydryl reductant Tris(2-carboxyethyl)phosphine
      (TCEP) for both nucleic acid and thiophosphate chemistry, including its effects
      on organomercurial gel electrophoresis, RNA catalysis, RNA backbone stability,
      and the intrinsic stability of TCEP. The sulfhydryls of dithiothreitol (DTT)
      compete with thiophosphates for binding to the mercury within [(N
      acryloylamino)phenyl] mercuric chloride (APM) polyacrylamide gels, whereas
      millimolar concentrations of TCEP gave no difference in the fraction of
      thiophosphorylated RNA retained on the APM interface relative to samples
      containing no reductant. Ribozyme activity in TCEP, assessed by the self
      thiophosphorylating Kin.46 ribozyme, was unaffected by the presence of DTT or
      TCEP or by the absence of reductant, as measured on APM gels and evaluated by
      Michaelis-Menten kinetics. Unexpectedly, TCEP more than doubled the half-life of
      full-length RNA at 50 and 70 degrees C, whether in 5 or 50mM MgCl(2), relative to
      DTT and the absence of reductant. Under these same conditions, the 5(')
      thiophosphate showed negligible decay, and TCEP was more stable than DTT. TCEP
      thermostability was equivalent in the presence of 5 or 50mM MgCl(2) and 10mM
      adenosine or ATP.

PMID- 14715295
TI  - Structure-based design of a fluorimetric redox active peptide probe.
AB  - Structure-based iterative design was used to prepare a disulfide-containing
      nonapeptide as a fluorimetric probe for chemical and biochemical disulfide
      forming and breaking reactions. The peptide is composed entirely of natural amino
      acids and exhibits a marked (42%) change in fluorescence between its oxidized and
      its reduced states. The probe is easily synthesized and highly water soluble and
      exhibits well-behaved kinetics on reduction with the reductant tris
      carboxyethylphosphine. The reduced peptide is an excellent substrate of the
      enzyme quiescin-sulfhydryl oxidase and may find utility in the characterization
      of other disulfide oxidoreductases.

PMID- 14715296
TI  - In vitro compartmentalization by double emulsions: sorting and gene enrichment by
      fluorescence activated cell sorting.
AB  - Water-in-oil (w/o) emulsions can be used to compartmentalize and select large
      gene libraries for a predetermined function. The aqueous droplets of the w/o
      emulsion function as cell-like compartments in each of which a single gene is
      transcribed and translated to give multiple copies of the protein (e.g., an
      enzyme) it encodes. While compartmentalization ensures that the gene, the protein
      it encodes, and the products of the activity of this protein remain linked, it
      does not directly afford a way of selecting for the desired activity. Here we
      show that re-emulsification of w/o emulsions gives water-in-oil-in-water (w/o/w)
      emulsions with an external (continuous) water phase through which droplets
      containing fluorescent markers can be isolated by fluorescence-activated cell
      sorting (FACS). These w/o/w emulsions can be sorted by FACS, while the content of
      the aqueous droplets of the primary w/o emulsion remains intact. Consequently,
      genes embedded in these water droplets together with a fluorescent marker can be
      isolated and enriched from an excess of genes embedded in water droplets without
      a fluorescent marker. The ability of FACS instruments to sort up to 40000 events
      per second may endow this technology a wide potential in the area of high
      throughput screening and the directed evolution of enzymes.

PMID- 14715297
TI  - Plasma lipid hydroperoxides measurement by an automated xylenol orange method.
AB  - Lipid hydroperoxides (LH) appear to be good candidates as initial biomarkers of
      oxidative stress. We describe an automated method to quantify it, based on a
      known principle: oxidation of Fe II to Fe III by lipid hydroperoxides, under
      acidic conditions, followed by complexation of Fe III by xylenol orange. This
      method requires only a 10-microl sample volume of heparinized plasma or serum. It
      has been carried out automatically, with two reagents, in a two-end-point mode
      with bichromatic detection at 570 and 700 nm. The within-run precision, measured
      on a low- and a high-level plasma, was 5.0+/-0.3 and 14.0+/-0.6 microM (n=25 for
      each series). The between-run precision (one run for 18 days), evaluated on two
      commercial controls, was 5.6+/-0.5 microM (CV=8.9%) and 7.9+/-0.5 microM
      (CV=6.3%). The recovery of known amounts of tert-butylhydroperoxide (1 and 2
      microM) added to human plasma was 98%. The specificity was demonstrated by the
      excellent correlation of the values of 42 samples measured either directly, with
      a simple dilution, or after gel permeation chromatography. The reference interval
      determined on 21 subjects was 4.9+/-1.7 microM. This was in the upper range of
      previously published values but our recovery and chromatographic experiments
      strongly suggest that former methods have underestimated the true content of LH
      in human plasma.

PMID- 14715298
TI  - Phosphotyrosine phosphoepitopes can be rapidly analyzed by coexpression of a
      tyrosine kinase in bacteria with a T7 bacteriophage display library.

PMID- 14715299
TI  - Determination of nitrite in biological fluids by use of electron spin resonance.

PMID- 14715300
TI  - Resolution of mixed human DNA samples using mitochondrial DNA sequence variants.

PMID- 14715301
TI  - Sensitive and specific detection of bovine immunodeficiency virus and bovine
      syncytial virus by 5' Taq nuclease assays with fluorescent 3' minor groove binder
      DNA probes.
AB  - Sensitive assays are required to detect bovine retroviruses in donor cattle used
      for the in vivo preparation of Australian tick fever vaccines. 5' Taq nuclease
      assays using 3' minor groove binder DNA probes (TaqMan)MGB) were developed and
      compared to conventional PCR assays for the sensitive detection of bovine
      syncytial virus (BSV) and bovine immunodeficiency virus (BIV). Seven beef and
      dairy herds were screened to evaluate these tests. Comparative sensitivities of
      PCR tests were determined by testing log(10) dilutions of plasmids with inserts
      containing corresponding provirus sequences. Published PCR assays targeting BIV
      env sequences did not adequately amplify Australian BIV sequences. Pol sequences
      from Australian strains of BIV and BSV were used to design TaqMan MGB assays,
      which improved sensitivity 10-fold (BIV) and 100-fold (BSV), respectively, over
      conventional PCR tests. This is the first report of Australian sequences of BIV
      and BSV and the first 5' Taq nuclease assays described to detect these viruses.
      These methods could be applied to future studies requiring sensitive detection of
      these two bovine retroviruses.

PMID- 14715302
TI  - Comparison of storage methods for reverse-transcriptase PCR amplification of
      rotavirus RNA from gorilla (Gorilla g. gorilla) fecal samples.
AB  - Detection of enteric viral nucleic acids in preserved gorilla fecal specimens was
      investigated using reverse transcription polymerase chain reaction (rt-PCR). A
      commercially available viral RNA extraction kit was used to isolate nucleic acids
      from captive gorilla fecal samples seeded with rotavirus and stored in ethanol,
      formalin, a commercial RNA preservation solution, guanidine thiocyanate buffer
      (GT), and samples dried in tubes containing silica gel. Nucleic acids were
      extracted at 1, 7, 70 and 180 days and used for rt-PCR amplification of specific
      rotavirus RNA sequences. Successful rt-PCR amplification of the target product
      varied according to storage conditions, and storage time. Only samples stored in
      GT gave 100% positive results at 180 days. It is recommended that fecal samples
      be collected in GT for viral RNA analysis.

PMID- 14715303
TI  - Species identification of all eight human herpesviruses with a single nested PCR
      assay.
AB  - There are eight currently known human herpesviruses, all of which are capable of
      latent persistence and reactivation following primary infection. Herpesvirus
      induced disease is common, widespread, and associated with significant morbidity,
      particularly in the immunocompromised human host. Current methods of herpesvirus
      detection include viral culture and polymerase chain reaction (PCR). A robust PCR
      method based upon amplification of the highly conserved herpesvirus DNA
      polymerase gene that is capable of detection of all eight human herpesviruses,
      including EBV and HHV-6 subtypes, from clinical material is described. Species
      identification of PCR products is accomplished by either of two methods,
      chemiluminescent dot blot hybridization and heteroduplex mobility shift assay,
      both of which allow for simultaneous detection of multiple herpesviruses. This
      method should prove useful for rapid and accurate species identification of all
      eight human herpesviruses from clinical material.

PMID- 14715305
TI  - Rapid RT-PCR amplification of full-length poliovirus genomes allows rapid
      discrimination between wild-type and recombinant vaccine-derived polioviruses.
AB  - Poliomyelitis outbreaks in areas that were free for a long time of wild-type
      polioviruses have been reported. Characterization at nucleotide level of the
      causative agents showed that the isolated viruses were recombinant oral polio
      vaccine (OPV)-derived polioviruses. To allow rapid identification and detailed
      analysis of such recombinant polioviruses, a robust full-length reverse
      transcriptase-PCR (RT-PCR) was developed using SuperScript II (RT) and expand
      (PCR). Without extensive purification, it was possible to amplify and
      characterize the full-length genomes of all selected vaccine, wild-type, and
      recombinant vaccine-derived polioviruses within a week. Endonuclease nuclease
      analysis (SpeI) of the full-length amplicons allowed easy discrimination between
      recombinant and non-recombinant polioviruses. Furthermore, sequence analysis of
      cloned full-length amplicons of a recombinant vaccine-derived poliovirus strain
      showed that the quasi-species nature of a viral stock is preserved during the RT
      PCR procedure. This robust and rapid RT-PCR method will allow rapid
      characterization of (recombinant) poliovirus strains in case of a local
      poliomyelitis outbreak, and will help to assess the risk of the appearance of
      such strains after wild-type poliovirus has been eradicated globally.

PMID- 14715304
TI  - A reporter-based assay for identifying hepatitis C virus inhibitors based on
      subgenomic replicon cells.
AB  - Hepatitis C virus (HCV) encodes a polyprotein that needs to be processed
      proteolytically by cellular and viral proteases into mature functional proteins.
      One of the viral proteins, NS3/4A, has serine protease activity that is critical
      for virus maturation. The generation and characterization of an engineered HCV
      replicon cell line (Ava5) is described which constitutively expresses
      EGdelta4AB)SEAP reporter protein and the cell line was designated as Ava5
      EG(delta4AB)SEAP. EG(delta4AB)SEAP is a fusion protein in which Enhanced Green
      Fluorescent Protein (EGFP) was fused to SEcreted Alkaline Phosphatase (SEAP)
      through the NS3/4A protease decapeptide recognition sequence, delta4AB, which
      spans the NS4A and NS4B junction region. The secretion of SEAP into culture
      medium has been shown to depend on the cleavage of delta4AB by HCV NS3/4A
      protease. It is demonstrated that the amount of NS3/4A in Ava5-EG(delta4AB)SEAP
      cells correlated well with the copy numbers of HCV subgenomic RNA. It is also
      shown that replication of HCV subgenomic RNA inside cells is reflected by the
      alkaline phosphatase (SEAP) levels in culture medium. SEAP activity in the
      culture medium of Ava5-EG(delta4AB)SEAP was approximately 50-fold higher than the
      parental Ava5 cells. Ava5-EG(delta4AB)SEAP was validated as a drug screening
      system since several known HCV inhibitors were shown to reduce SEAP activities in
      culture media of Ava5-EG(delta4AB)SEAP cells. In conclusion, Ava5
      EG(delta4AB)SEAP cells can be used to monitor HCV sub-genomic replication and the
      assay can be readily adapted to high throughput screening format to identify
      prospective anti-HCV drugs.

PMID- 14715306
TI  - Development and evaluation of a quantitative competitive reverse transcription
      polymerase chain reaction (RT-PCR) for hepatitis C virus RNA in serum using
      transcribed thio-RNA as internal control.
AB  - A method for quantitation of hepatitis C virus (HCV) RNA was developed based on
      competitive reverse transcription polymerase chain reaction (RT-PCR) using in
      vitro transcribed mutated thio-RNA as a competitor template. The thio-RNA is more
      resistant to RNAse and is stable over a year. This assay was compared with the
      commercially available Roche Amplicor HCV Monitor assay V 2.0 and real time PCR
      using SYBR green 1 dye method. A total of 18 pre-therapy serum samples from
      chronic hepatitis C cases were tested in parallel by the three assays. All
      samples could be quantitated using the in-house competitive RT-PCR and real time
      PCR and there was a significant correlation in the virus titer (P<0.05). However,
      8 (44%) samples could not be quantified by Amplicor HCV Monitor assay, which has
      a lower detection range (10(2) to 10(5.5) copies/ml). The in-house method of
      competitive RT-PCR showed a detection range of 10(3) to 10(10) copies/ml. In the
      patients the mean viral titer was found to be (9.66+/-9.3)x10(6) copies/ml. Ten
      (55%) of the samples, assessed by the Amplicor HCV Monitor assay showed a mean
      viral titre of (1.13+/-0.75)x10(6) copies/ml, which was lower than the other two
      tests. The competitive PCR method and real time PCR could amplify all prevalent
      genotypes. This in-house quantitative competitive RT-PCR method is simple, cheap,
      reproducible and useful for estimation of HCV RNA load.

PMID- 14715307
TI  - Recombinant VP9-based enzyme-linked immunosorbent assay for detection of
      immunoglobulin G antibodies to Banna virus (genus Seadornavirus).
AB  - Banna virus (BAV, genus Seadornavirus, family Reoviridae) is an arbovirus
      suspected to be responsible for encephalitis in humans. Two genotypes of this
      virus are distinguishable: A (Chinese isolate, BAV-Ch) and B (Indonesian isolate,
      BAV-In6969) which exhibit only 41% amino-acid identity in the sequence of their
      VP9. The VP7 to VP12 of BAV-Ch and VP9 of BAV-In6969 were expressed in bacteria
      using pGEX-4T-2 vector. VP9 was chosen to establish an ELISA for BAV, based
      mainly on two observations: (i). VP9 is a major protein in virus-infected cells
      and is a capsid protein (ii). among all the proteins expressed, VP9 was obtained
      in high amount and showed the highest immuno-reactivity to anti-BAV ascitic
      fluid. The VP9s ELISA was evaluated in three populations: French blood donors and
      two populations (blood donors and patients with a neurological syndrome) from
      Malaysia, representing the region where the virus was isolated in the past. The
      specificity of this ELISA was >98%. In mice injected with live BAV, the assay
      detected IgG-antibody to BAV infection 21 days post-injection, which was
      confirmed by Western blot using BAV-infected cells. The VP9 ELISA permits to
      determine the sero-status of a population without special safety precautions and
      without any requirements to propagate the BAV. This test should be a useful tool
      for epidemiological survey of BAV.

PMID- 14715308
TI  - A SYBR green, real-time RT-PCR method to detect and quantitate Norwalk virus in
      stools.
AB  - A simple, single tube, hot start, real-time reverse transcription-PCR (rt RT-PCR)
      technique using SYBR green fluorescence was developed for the detection of
      genogroup I, cluster 1 Norwalk virus (NV) in stools. Sample dilution and heat
      release of viral RNA was effective as an alternative to more complex procedures
      to extract viruses from stool specimens. Real-time RT-PCR was applied to 68 stool
      isolates from patients participating in a NV volunteer study. First derivative
      melt curves were used to verify NV amplicon and to rule out the presence of
      primer dimer or spurious product. A dilution end-point standard curve was
      developed to semi-quantitate minimum virus levels and the results showed the
      number of RT-PCR amplifiable NV as high as 6.16 x 10(10)g(-1) of stool. The
      application of these methods was instrumental in identifying three asymptomatic
      patients who shed viruses in their stools, thus demonstrating a carrier state
      among seemingly healthy individuals. This study serves as a model for the
      development of rapid and specific detection, verification, and quantitation
      procedures for other Noroviruses in stools.

PMID- 14715309
TI  - Cell-based assay for the determination of temperature sensitive and cold adapted
      phenotypes of influenza viruses.
AB  - The determination of temperature sensitive (ts) and cold adapted (ca) phenotype
      for influenza A and B strains has been conducted traditionally using embryonated
      chicken eggs. As attempts are made to move away from the use of eggs in the
      manufacturing process of influenza vaccines, it will become useful to develop
      cell-based assays to support cell culture-based vaccine production. In this
      study, MDCK cells have been evaluated as a tool for determining the ts and ca
      phenotypes associated with live attenuated influenza viruses. Direct comparisons
      were made of these phenotypes carried out in eggs. Reassortants made from the
      Russian live attenuated influenza donor strains A/Leningrad/134/17/57 (H2N2) and
      B/USSR/60/69 were prepared entirely in MDCK cells and their phenotypes evaluated
      using the MDCK cell-based assay. It is concluded that MDCK cells are more
      sensitive than eggs for the measurement of ts and ca phenotype of influenza
      viruses (particularly for influenza A) and they provide an alternative means for
      screening candidate reassortants prior to determining their genome composition.

PMID- 14715310
TI  - Detection of wild type and deleted latent membrane protein 1 (LMP1) of Epstein
      Barr virus in clinical biopsy material.
AB  - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is one of two
      postulated viral oncogenic proteins. Sequence variations, and in particular a 30
      base pair deletion variant called CAO, may define different disease populations.
      We developed a panel of rat monoclonal antibodies (MAb) specific for the non-wild
      type LMP1 and compared the presence of the antibody staining with LMP1 DNA
      sequence analysis on clinical samples of nasopharyngeal carcinoma, peripheral T
      cell lymphoma (PTCL), Hodgkin's disease, lymphoblastoid cell lines (LCL) from
      normal volunteers, and patients with nasopharyngeal carcinoma. The results
      demonstrate specificity of the monoclonal cocktail for detecting the non-wild
      type LMP1 and the ability to sub-differentiate between the mediterranean type of
      LMP1 and the CAO-LMP1. Double immunofluorescence on paraffin material using the
      traditional CS1-4 monoclonal antibodies and the CAO-cocktail revealed no dual
      population of cells in the biopsy material from the Asian region.

PMID- 14715311
TI  - Replication of white spot syndrome virus in ovarian primary cultures from the
      kuruma shrimp, Marsupenaeus japonicus.
AB  - Propagation of white spot syndrome virus (WSSV) was investigated in primary
      ovarian cultures from the kuruma shrimp Marsupenaeus japonicus. A WSSV strain,
      purified by sucrose density gradient centrifugation, was inoculated into 10-day
      old primary ovarian cultures. WSSV infection induced marked cytopathic effect
      (CPE) on primary ovarian cells. Initially, virus-infected cells began to shrink
      72 h post-inoculation, followed by the rounding of most cells which detached
      finally from flask surface. Electron microscopic observations clearly showed that
      the replication of WSSV occurred in nuclei of ovarian cells. Immunoblot analysis
      with antibodies against the WSSV envelope protein VP28 provided the evidence that
      the levels of WSSV antigens in culture supernatant gradually increased during the
      period between 24 and 120 h after virus inoculation. The results suggest that the
      use of primary ovarian cultures of the kuruma shrimp will facilitate
      characterization of the WSSV infection.

PMID- 14715312
TI  - Isolation of putative dengue virus receptor molecules by affinity chromatography
      using a recombinant E protein ligand.
AB  - Nucleotide sequences coding for the full-length envelope (E) glycoprotein gene of
      dengue virus type 4 was amplified using an RT-PCR method from infected C6/36
      cells and cloned into pPROEx-Hta expression vector. The expression of the
      recombinant E protein in Escherichia coli was confirmed by Western blot using a
      polyclonal anti-dengue polyclonal antibody. The His-tagged fusion protein was
      obtained from the bacterial cellular extracts in almost pure form by immobilized
      metal affinity chromatography and the recombinant protein retained its ability to
      bind to 40 and 45 kDa proteins, previously described as putative receptors for
      dengue virus in C6/36 cells. To purify the 40 and 45 kDa molecules, a total
      protein extract from C6/36 cells was passed through an affinity chromatography
      column using immobilized recombinant E protein. After washing with isotonic
      buffer, elution was accomplished using a high salt buffer. The two proteins
      obtained, with molecular weights of 40 and 45 kDa, were recognized by dengue 4
      virus, in virus overlay protein binding assay. This procedure allows further
      characterization of molecules that could be involved in dengue binding and entry.

PMID- 14715313
TI  - Strand specific quantitative real-time PCR to study replication of hepatitis C
      virus genome.
AB  - Qualitative detection of negative hepatitis C virus (HCV) RNA has been used
      widely to demonstrate HCV replication. However, relative quantitation of both
      positive and negative HCV RNA strands has never been reported for studying viral
      genome replication. A strand specific real-time PCR carried out in the highly
      conserved 5'-non-coding region of HCV genome and monitored either by the DNA
      binding dye SYBR Green I or by molecular beacons is described. Using these
      techniques, it was found that negative HCV RNA strand was a 100-1000 times less
      abundant than the positive strand in the liver of HCV infected patients.

PMID- 14715314
TI  - The use of mass spectrometry in genomics.
AB  - Recent advances in the development of electrospray ionization (ESI) and matrix
      assisted laser desorption/ionization (MALDI) now permit the near routine analysis
      of oligonucleotides and intact nucleic acids. These developments have led to the
      use of mass spectrometry (MS) as a detection platform for genomics studies. Among
      the various uses of mass spectrometry in genomics, applications focused on the
      characterization of single nucleotide polymorphisms (SNPs) and short tandem
      repeats (STRs) are particularly well-suited to MALDI or ESI-based analysis. It is
      predicted that continued developments in methodology and instrumentation will
      further improve the capabilities of mass spectrometry for nucleic acid analysis.

PMID- 14715315
TI  - Cloning and sequence analysis of the Candida utilis HIS3 gene.
AB  - A DNA fragment, carrying the Candida utilis HIS3 gene, has been isolated from a
      genomic DNA library by complementation of the E. coli hisB mutant. Its nucleotide
      sequence was determined and it predicts a single open reading frame of 675 bp
      (224 aa). The deduced amino acid sequence is highly homologous to other yeast and
      fungi HIS3 genes.

PMID- 14715316
TI  - PCR-generated artificial ribosomal DNAs from premature termination at Alu
      sequences.
AB  - PCR-amplified product may sometimes not correlate with a DNA state in vivo due to
      formation of recombinant molecules. Here we show that recombinant product can
      form in vitro on amplifying the region upstream of the rRNA transcription start
      point in human ribosomal intergenic spacer. These results provide the first
      information concerning definite Alu sites where premature polymerase termination
      occurs.

PMID- 14715317
TI  - Modified location of the major histocompatibility protein Kb by co-delivery with
      VP22 protein.
AB  - We report the construction of an expression vector pVP22::Kb that encodes a
      chimeric protein composed of VP22 and murine major histocompatibility complex
      class I molecule, Kb. Flow cytometry assays show that VP22 modifies normal cell
      surface localization of Kb protein.

PMID- 14715318
TI  - Effect of genetic circular permutation near the active site on the activity and
      stability of an enzyme inhibitor.
AB  - We report here the effect of circular permutation on the structure and function
      of a model protein tendamistat, a 74 amino acid competitive inhibitor of porcine
      pancreatic alpha-amylase. The activity and stability of wild type and two
      permuted tendamistat variants were characterized by measurement of alpha-amylase
      kinetic and thermodynamic binding parameters and their thermodynamics of
      unfolding. Our results show that large variations in structure and function can
      occur upon circularly permuting tendamistat near its active site that are not
      obvious, a priori, from the structure of the native protein and we propose a
      structural thermodynamic explanation of the experimental observations.

PMID- 14715319
TI  - Chest radiography for the diagnosis of acute aortic syndrome.
AB  - PURPOSE: We sought to assess the diagnostic accuracy of routine chest radiography
      for the acute aortic syndrome (dissection, intramural hematoma, penetrating
      ulcer, or nondissecting aneurysm). METHODS: During a 6-year period, 216 patients
      (143 men, 73 women; mean [+/- SD] age, 58 +/- 17 years) underwent chest
      radiography for suspected acute aortic syndrome. Chest films were re-evaluated
      blindly for aortic disease, based on an overall impression using standard
      criteria such as widening of the aortic contour and mediastinal shadow. Findings
      were matched to tomographic images, anatomical inspection, or both, as the
      criterion standard; aortic disease was confirmed in 109 (50%) of the patients.
      RESULTS: Chest radiography had a sensitivity of 64% (70/109) and a specificity of
      86% (92/107) for aortic disease. Sensitivity was 67% (38/57) for overt aortic
      dissection, 61% (22/36) for nondissecting aneurysm, and 63% (10/16) for
      intramural hemorrhage or penetrating ulcer. However, sensitivity was lower for
      pathology confined to the proximal aorta (47% [21/45]) than for disease involving
      distal aortic segments (77% [49/64]). A receiver operating characteristic curve
      analysis of aortic diameters failed to identify a threshold for the diagnosis of
      aortic disease. CONCLUSION: Chest radiography is of limited value for diagnosing
      the acute aortic syndrome, particularly for conditions confined to the ascending
      aorta. Since a definitive diagnosis is required in any patient with clinically
      suspected acute aortic syndrome, routine chest radiography should be replaced by
      tomographic aortic imaging.

PMID- 14715320
TI  - Electrocardiographic abnormalities in patients with diphtheria: a prospective
      study.
AB  - PURPOSE: To determine the incidence of and risk factors for electrocardiographic
      (ECG) abnormalities in adults with diphtheria. METHODS: A prospective study was
      conducted involving 122 adult patients with respiratory tract diphtheria.
      Diphtheria was confirmed by isolation of a toxin-producing strain of
      Corynebacterium diphtheriae. Patients had serial clinical evaluations and ECGs
      for a minimum of 21 days. RESULTS: Cardiac involvement was detected in 25 (28%)
      of 88 evaluable patients, with a median time from symptom onset to an abnormal
      ECG of 9 days (range, 4 to 24 days). In a logistic regression analysis, age (odds
      ratio [OR] = 4.1; 95% confidence interval [CI]: 1.6 to 11.0), shared
      accommodation (OR = 2.9; 95% CI: 1.0 to 8.6), fever (OR = 4.2; 95% CI: 1.1 to
      16.6), and extensive respiratory tract infection with subcutaneous edema (OR =
      7.0; 95% CI: 1.2 to 42.2) were independent risk factors for cardiac involvement.
      CONCLUSION: Cardiac involvement is a common complication of respiratory tract
      infection with C. diphtheriae, and occurs more often among older patients, those
      with lower socioeconomic status, and those with severe respiratory tract
      involvement.

PMID- 14715321
TI  - The effect of helical computed tomography on diagnostic and treatment strategies
      in patients with suspected pulmonary embolism.
AB  - BACKGROUND: Helical computed tomography (CT) has been proposed as a first-line
      test for the diagnosis of pulmonary embolism. How the test affects the diagnostic
      evaluation of patients with suspected pulmonary embolism is unknown. METHODS: We
      examined a cohort of 360 patients evaluated for pulmonary embolism at a teaching
      hospital in the 4 years following the introduction of the helical CT scan. We
      collected patient demographic and clinical data to calculate the pretest
      likelihood of pulmonary embolism; we then read the test results and determined
      rates of further testing and treatment for pulmonary embolism. RESULTS: After the
      helical CT scan became available, the number of patients referred for pulmonary
      embolism testing increased markedly from 170 to 624 total evaluations during 1997
      to 2000 (P <0.01). This rise was due to increased use of the helical CT scan (9%
      to 83% of evaluations, P <0.01) as the use of ventilation-perfusion scanning (79%
      to 17%, P = 0.03) and pulmonary angiography (12% to <1%, P <0.01) fell. There was
      no change in the pre-test likelihood of disease over time, but the percentage of
      scans that were positive for pulmonary embolism rose (14% to 32%, P =0.02).
      Clinicians treated all patients who had a positive CT scan, but became less
      likely over time to order further testing for patients who had a negative scan
      (30% to 12%, P = 0.02). CONCLUSION: At this academic medical center, introduction
      of the helical CT scan had a profound effect on the evaluation of pulmonary
      embolism, resulting in more frequent use of the CT scan, and more frequent
      diagnosis and treatment of pulmonary embolism, despite no change in the pretest
      probability of disease. Future studies should confirm our findings and determine
      whether increased detection of pulmonary emboli results in improved outcomes.

PMID- 14715322
TI  - Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the
      response to melatonin replacement therapy.
AB  - PURPOSE: Melatonin, which is produced by the pineal gland at night, is an
      endogenous sleep regulator. Both sleep disorders and impaired melatonin
      production are common among the elderly. We examined the excretion of the major
      melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged >or=55 years
      and its relation with the subsequent response to melatonin therapy. METHODS: We
      studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy
      volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between
      10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were
      treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of
      controlled-release melatonin, of which 372 provided complete datasets. Clinical
      response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as
      an improvement of 10 mm or more on the visual analog scales. RESULTS: Mean (+/-
      SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 +/-
      8.3 microg per night) than in volunteers of the same age (18.1 +/- 12.7 microg
      per night, P <0.05) and in younger volunteers (24.2 +/- 11.9 microg per night, P
      <0.05). About 30% of patients (112/372) excreted <or=3.5 microg of
      sulfatoxymelatonin per night, which is considered to be lower than normal for
      this age group. These "low excretors" had a significantly higher response to
      melatonin replacement therapy (58% [65/112] vs. 47% [122/260], P <0.05).
      CONCLUSION: Low nocturnal melatonin production is associated with insomnia in
      patients aged 55 years or older, and identifies patients who are somewhat more
      likely to respond to melatonin replacement.

PMID- 14715323
TI  - Association between long-term statin use and mortality after successful abdominal
      aortic aneurysm surgery.
AB  - PURPOSE: To assess the potential long-term beneficial effects of statin use after
      successful abdominal aortic surgery. METHODS: Between 1991 and 2001, 570 patients
      underwent abdominal aortic aneurysm repair at the Erasmus Medical Center. Of the
      519 patients (91%) who survived surgery beyond 30 days, 510 (98%) were followed
      for a median of 4.7 years (interquartile range, 2.7 to 7.3 years). These patients
      were evaluated for use of statins and beta-blockers, and for clinical risk
      factors (e.g., advanced age; prior myocardial infarction; diabetes mellitus;
      renal dysfunction; chronic pulmonary disease; history of heart failure, stroke,
      or angina), and their association with all-cause and cardiovascular mortality.
      RESULTS: A total of 205 patients (40%) died during follow-up; 140 due to
      cardiovascular causes. The incidence of all-cause (18% [27/154] vs. 50%
      [178/356], P <0.001) and cardiovascular (11% [17/154] vs. 34% [122/356], P
      <0.001) mortality was significantly lower in statin users than in nonstatin
      users. After adjusting for clinical risk factors and beta-blocker use, the
      association between statin use and reduced all-cause (hazard ratio [HR] = 0.4;
      95% confidence interval [CI]: 0.3 to 0.6; P <0.001) and cardiovascular (HR = 0.3;
      95% CI: 0.2 to 0.6; P <0.001) mortality persisted. Beta-blocker use was also
      associated with a significant reduction in all-cause (HR = 0.6; 95% CI: 0.5 to
      0.9; P = 0.003) and cardiovascular (HR = 0.7; 95% CI: 0.4 to 0.9; P = 0.03)
      mortality. There was no evidence of an association between statin use and all
      cause and cardiovascular mortality according to beta-blocker use or clinical risk
      factors. CONCLUSION: Long-term statin use is associated with reduced all-cause
      and cardiovascular mortality irrespective of clinical risk factors and beta
      blocker use.

PMID- 14715324
TI  - Economic effects of beta-blocker therapy in patients with heart failure.
AB  - PURPOSE: Studies suggest that beta-blockers improve outcomes in heart failure
      patients and may be cost saving to society. However, many heart failure patients
      are not treated with beta-blockers. Economic incentives facing hospitals,
      physicians, payers, and patients may not encourage treatment adoption. We
      assessed the economic effects of beta-blocker therapy from various perspectives:
      societal, Medicare, hospital, physician, and patient. METHODS: A Markov model of
      heart failure progression over 5 years was developed. Transition probabilities
      and the effect of beta-blockers on mortality and hospitalization were based on
      clinical trial data. Estimates of hospital costs and reimbursement were obtained
      from the Duke University Medical Center. Physician fees were based on the
      Medicare fee schedule. RESULTS: Beta-blocker therapy increased survival by 0.3
      years per patient and reduced societal costs by US dollars 3959 per patient over
      5 years. Medicare costs declined by US dollars 6064 per patient, due primarily to
      lower hospitalization rates. Unless heart failure admissions could be replaced
      with other hospitalizations that generated an equal or greater revenue above
      variable cost, hospital revenue would be negatively affected. Physician revenue
      from treating heart failure patients would also decline. Patient costs increased
      with beta-blocker use (US dollars 2113 over 5 years). CONCLUSION: Beta-blocker
      therapy improves the clinical outcomes of heart failure patients and is cost
      saving to society and Medicare. However, hospitals and physicians have no clear
      financial incentives to support increased beta-blocker use. Changes in practice
      patterns could be encouraged by linking reimbursement with evidence-based care
      and covering patients' medication costs.

PMID- 14715325
TI  - Silent myocardial ischemia: concepts and controversies.
AB  - Silent myocardial ischemia is a relatively common, but poorly understood,
      clinical entity. The most accurate means of detecting silent myocardial ischemia
      and the precise treatment endpoints remain unclear. However, the amount of
      ischemic myocardium appears to correlate with the likelihood of future adverse
      cardiac events. Evidence suggests that patients at highest risk of severe
      myocardial ischemia, even in the absence of symptoms, derive the greatest benefit
      from an aggressive diagnostic and therapeutic approach. This paper reviews the
      diagnosis and treatment of silent myocardial ischemia, and its clinical
      implication in select patient groups: those without coronary artery disease,
      those with coronary artery disease, diabetic patients, postrevascularization
      patients, and women.

PMID- 14715326
TI  - Integrating antithrombin and antiplatelet therapies with early invasive
      management for non-ST-segment elevation acute coronary syndromes.
AB  - Non-ST-segment elevation acute coronary syndromes are a dramatic manifestation of
      coronary artery disease. Multiple clinical trials have shown that early cardiac
      catheterization improves clinical outcomes in patients with non-ST-segment
      elevation acute coronary syndromes. Many antithrombotic agents effectively manage
      unstable coronary syndromes and serve as adjuncts to percutaneous coronary
      intervention. Yet, the growing number of pharmacologic agents makes early
      management of non-ST-segment elevation acute coronary syndromes increasingly
      complex. We review the current evidence regarding the optimal integration of
      early antithrombotic and antiplatelet therapies with early coronary angiography
      and subsequent revascularization.

PMID- 14715327
TI  - Effect of community pharmacist intervention on cholesterol levels in patients at
      high risk of cardiovascular events: the Second Study of Cardiovascular Risk
      Intervention by Pharmacists (SCRIP-plus).

PMID- 14715328
TI  - Modern imaging of the acute aortic syndrome.

PMID- 14715329
TI  - Beta-blockers for heart failure: who should pay?

PMID- 14715330
TI  - Cognitive impairment and mortality in elderly patients with heart failure.

PMID- 14715332
TI  - Cervico-cranial artery dissection and antiphospholipid syndrome: is there a link?

PMID- 14715333
TI  - One blow too many.

PMID- 14715334
TI  - Reflections on being a Chair of Medicine, 1993 to 2001 - Part 2.

PMID- 14715335
TI  - Assessment of quality of life and cognitive function after out-of-hospital
      cardiac arrest with successful resuscitation.
AB  - This prospective cohort study evaluated the impact of the time-related elements
      of the "chain of survival" on the quality of life of patients, taking their
      characteristics into account. Between 1995 and 2002, consecutive, out-of-hospital
      cardiac arrest patients from Amsterdam and the surrounding areas were included in
      this study. A total of 227 patients (12%) survived to hospital discharge and 174
      were definitive survivors who were available for assessment at 6 months. Quality
      of life was measured with the 136-item Sickness Impact Profile (SIP); cognitive
      functioning was assessed through the Mini Mental State Examination. SIP profiles
      were compared with profiles of an open Dutch population of the elderly and
      patients who experienced a stroke. Time intervals of the chain of survival were
      calculated from the estimated moment of collapse and related to outcome using
      regression analysis. The SIP profile of survivors was a little above the
      reference profile, indicating a slightly poorer quality of life, and below the
      profile of patients after stroke, indicating a better quality of life. Impaired
      cognitive function was associated with delay in the start of cardiopulmonary
      resuscitation (odds ratio 4.3, 95% confidence interval 1.0 to 19). Absence of the
      need for advanced cardiopulmonary life support was associated with better
      cognitive functioning (odds ratio 0.3, 95% confidence interval 0.1 to 0.9).
      Female gender and older age were associated with impaired physical functioning.
      Trends were found for better outcomes after early access, immediate
      resuscitation, early defibrillation, and early advanced care.

PMID- 14715336
TI  - The metabolic syndrome and risk of major coronary events in the Scandinavian
      Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis
      Prevention Study (AFCAPS/TexCAPS).
AB  - The metabolic syndrome, which is a set of lipid and nonlipid risk factors of
      metabolic origin linked with insulin resistance, is believed to be associated
      with an elevated risk for cardiovascular disease, but few have studied this
      association in prospective long-term cardiovascular outcomes trials. Placebo data
      from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas
      Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) were used post hoc to
      estimate the long-term relative risk of major coronary events (MCEs) associated
      with the metabolic syndrome, after excluding diabetes mellitus. In 4S and
      AFCAPS/TexCAPS, respectively, placebo-treated patients with the metabolic
      syndrome were 1.5 (95% confidence interval 1.2 to 1.8) and 1.4 (95% confidence
      interval 1.04 to 1.9) times more likely to have MCEs than those without it. Of
      the components of the metabolic syndrome, low high-density lipoprotein levels
      were associated with elevated risk of MCEs in both studies, whereas high
      triglycerides in 4S and elevated blood pressure and obesity in AFCAPS/TexCAPS
      were associated with significantly increased relative risk. Patients with the
      metabolic syndrome showed increased risk of MCEs irrespective of their Framingham
      calculated 10-year risk score category (>20% vs </=20%). These data demonstrate
      that the metabolic syndrome is associated with increased risk of MCEs in both
      hypercholesterolemic patients with coronary heart disease in 4S and in those with
      low high-density lipoprotein cholesterol but without coronary heart disease in
      AFCAPS/TexCAPS. It appears that the metabolic syndrome is associated with risk
      that is not entirely accounted for by traditional risk scoring paradigms.

PMID- 14715337
TI  - Use of tissue Doppler imaging to facilitate the prediction of events in patients
      with abnormal left ventricular function by dobutamine echocardiography.
AB  - The extent of abnormality in patients with positive dobutamine echocardiography
      (DE) is predictive of risk, but the wall motion score (WMS) has low concordance
      among observers. We sought whether quantifying the extent of abnormal wall motion
      using tissue Doppler (TD) could guide risk assessment in patients with abnormal
      DE in 576 patients with known or suspected coronary artery disease; standard DE
      was combined with color TD imaging at peak dose. WMS was assessed by an expert
      observer and studies were identified as abnormal in the presence of >/=1 segments
      with resting or stress-induced wall motion abnormalities. Patients with abnormal
      DE had peak systolic velocity measured in each segment. Tissue tracking was used
      to measure myocardial displacement. Follow-up for death or infarction was
      performed after 16 +/- 12 months. Of 251 patients with abnormal DE, 22 patients
      died (20 from cardiac causes) and 7 had nonfatal myocardial infarctions. The
      average WMS in patients with events was 1.8 +/- 0.5, compared with 1.7 +/- 0.5 in
      patients without events (p = NS). The average systolic velocity in patients with
      events was 4.9 +/- 1.7 cm/s and 6.4 +/- 6.5 cm/s in the patients without events
      (p <0.001). The average tissue tracking in patients with events was 4.5 +/- 1.5
      mm and was significant (5.7 +/- 3.1 mm) in those without events (p <0.001). Thus,
      TD is an alternative to WMS for quantifying the total extent of abnormal left
      ventricular function at DE, and appears to be superior for predicting adverse
      outcomes.

PMID- 14715338
TI  - Efficacy and safety of sildenafil citrate in men with erectile dysfunction and
      stable coronary artery disease.
AB  - This was a double-blind, placebo-controlled, flexible-dose study of the efficacy
      and safety of sildenafil in men with erectile dysfunction (ED) and clinically
      stable coronary artery disease (CAD). Patients were randomized to receive
      sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of
      the International Index of Erectile Function (IIEF). Secondary outcomes included
      the other IIEF questions and functional domains, the Life Satisfaction Checklist,
      the Erectile Dysfunction Inventory of Treatment Satisfaction, 2 global efficacy
      assessment questions, and intercourse success rate. By week 12, sildenafil
      treated patients (n = 70) showed significant improvements on questions 3 and 4
      compared with placebo-treated patients (n = 72; p <0.01). Larger percentages of
      sildenafil-treated patients reported improved erections (64%) and improved
      intercourse (65%) compared with placebo-treated patients (21% and 19%,
      respectively). Sildenafil-treated patients were highly satisfied with treatment
      and their sexual life compared with placebo-treated patients. Forty-seven percent
      of sildenafil- and 32% of placebo-treated patients experienced adverse events,
      including transient headache, hypertension, flushing, and dyspepsia. There were
      no serious drug-related cardiovascular effects. Thus, sildenafil is an effective
      and well-tolerated treatment for ED in men with CAD. Sildenafil was not
      associated with additional safety risks in this patient population.

PMID- 14715339
TI  - Treating to New Targets (TNT) Study: does lowering low-density lipoprotein
      cholesterol levels below currently recommended guidelines yield incremental
      clinical benefit?
AB  - The Treating to New Targets (TNT) trial is a parallel-group study that has
      randomized 10,003 patients from 14 countries to double-blind treatment with
      either atorvastatin 10 or 80 mg. During the double-blind period, low-density
      lipoprotein (LDL) cholesterol levels are expected to reach approximate mean
      values of 100 mg/dl (2.6 mmol/L) for the low-dose atorvastatin group and 75 mg/dl
      (1.9 mmol/L) for the high-dose group. Randomized patients are expected to be
      followed for an average of 5 years. The primary end point is the time to
      occurrence of a major cardiovascular event, defined as coronary heart disease
      death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke.
      The large patient numbers in the TNT study and long follow-up should ensure that
      there is adequate power to definitively determine if reducing LDL cholesterol
      levels to approximately 75 mg/dl (1.9 mmol/L) can provide additional clinical
      benefit.

PMID- 14715340
TI  - Effect of increasing metabolic syndrome score on atherosclerotic risk profile and
      coronary artery disease angiographic severity.
AB  - The metabolic syndrome (MS) is a frequent cause of coronary artery disease (CAD),
      and recently the National Cholesterol Education Program Adult Treatment Panel III
      suggested its diagnosis in the presence of 3 to 5 quantitatively defined markers.
      Because the consequences of the MS are likely related to the number and diversity
      of markers, we studied the relation between the number of markers-the MS score
      and the degree of abdominal obesity, risk factor profile, and severity of CAD.
      One thousand one hundred eight subjects of a mostly white population with
      symptoms of CAD (793 men and 315 women; 58.1 +/- 9.8 years of age) were divided
      into 6 groups based on their MS scores. A low high-density lipoprotein
      cholesterol level was the most frequently observed marker, followed by increased
      blood pressure, triglycerides, waist circumference, and fasting glucose. As the
      MS score increased so did abdominal obesity, parameters of "nontraditional"
      dyslipidemia with surrogate markers of dense low-density lipoprotein and high
      density lipoprotein particles, blood pressure, fasting glucose, insulin, and the
      homeostatic model assessment insulin resistance index. Similarly, an increasing
      MS score was significantly related to more severe coronary angiographic
      alterations and higher frequencies of unstable angina, myocardial infarction,
      percutaneous coronary intervention, and coronary artery bypass grafting.
      Therefore, the MS score provides a clinically useful index of MS severity and the
      associated atherosclerotic risk factor profile. It also correlates with the
      angiographic severity of CAD and its clinical complications.

PMID- 14715341
TI  - Comparison of left atrial volume and function after linear ablation and after
      cardioversion for chronic atrial fibrillation.
AB  - Several techniques for treatment of atrial fibrillation (AF) have been developed,
      including the direct placement of radiofrequency for lesions at open heart
      surgery. Detailed evaluation of left atrial (LA) function has not been performed
      after these procedures and has not been compared in patients with chronic AF. We
      compared the atrial function of patients with sustained sinus rhythm (SR) after
      linear ablation with a group who underwent direct-current cardioversion and a
      group of normal controls to investigate the measurable deleterious effects, if
      any, on atrial function after the surgical procedure. Twenty-one consecutive
      patients who had maintained SR for >6 months after a linear radiofrequency
      ablation (LRFA) procedure were studied. As control subjects, we examined 33
      patients with chronic AF successfully restored to SR by cardioversion who
      maintained SR for >6 months and 42 age-matched normal subjects. LA function was
      decreased in both the LRFA and cardioverted AF groups compared with normal
      controls. The parameters of LA function, atrial fraction, LA ejection fraction,
      and the A' velocity were lowest in the LRFA group, intermediate in the
      cardioverted AF group, and highest in the normal controls (LA function: 15.8 +/-
      10%, 26 +/- 10%, 33 +/- 7%; p = 0.0001; LA ejection fraction: 31 +13%, 41 +/-
      12%, 51 +/- 9%; p = 0.0001; A' velocity: 4.2 +/- 1.4, 7.6 +/- 2.2, 9.5 +/- 1.9
      cm/s; p = 0.0001). LA volumes were increased in the LRFA and cardioverted AF
      groups compared with normals (62.8 +/- 22 vs 70.6 +/- 17 vs 38.7 +/- 9.8 ml; p =
      0.0001). Thus, although LA function is restored and maintained after LRFA has
      been performed during open heart surgery, LRFA use is associated with a
      measurable decrease in LA function over and above that found after conventional
      cardioversion.

PMID- 14715342
TI  - Conduction system abnormalities in patients with obstructive hypertrophic
      cardiomyopathy following septal reduction interventions.
AB  - We observed the impact of percutaneous transluminal septal myocardial ablation
      (PTSMA) and myectomy on the conduction system in patients with obstructive
      hypertrophic cardiomyopathy (HC). Septal reduction intervention is capable of
      eliminating the left ventricular outflow tract obstruction in patients with
      obstructive HC; however, conduction system abnormalities are frequent
      consequences of these procedures. A standard 12-lead electrocardiogram and
      Doppler echocardiogram were obtained in 204 patients who underwent PTSMA (n = 70)
      or myectomy (n = 134) before and at average of 3 months after intervention. Of
      146 patients who had normal conduction systems before intervention, the duration
      of the QRS complex was significantly prolonged from 98 +/- 15 to 130 +/- 25 ms (p
      <0.0001), with right bundle branch block (RBBB) developing in 62% patients after
      PTSMA, and from 100 +/- 13 to 154 +/- 20 ms (p <0.0001), with left bundle branch
      block (LBBB) developing in 93% patients after myectomy. No significant difference
      in the QRS duration was found in the remaining 58 patients who had preexisting
      conduction abnormalities after intervention. In 174 patients without a
      preexisting permanent pacemaker, a pacemaker was implanted in 22% versus 13% of
      patients who underwent PTSMA (overall and without preexisting conduction block,
      respectively) and 10% versus 2% of patients with myectomy. The duration of
      baseline QRS was an independent predictor for the requirement of a permanent
      pacemaker (p <0.0001). Thus, RBBB often develops after PTSMA and LBBB is very
      frequently produced by myectomy. A possible requirement of a permanent pacemaker
      should always be considered before intervention when patients have preexisting
      RBBB or LBBB.

PMID- 14715343
TI  - Professor Sir Magdi Habib Yacoub, FRS, FRCS, FRCP, DS: a conversation with the
      editor. Interview by William Clifford Roberts.

PMID- 14715344
TI  - Population implications of changes in lipid management in patients with coronary
      heart disease.
AB  - Pharmacologic treatment and goal attainment rates from published literature
      indicate that lipid management has generally improved for patients with coronary
      heart disease. The population implications of these changes in lipid management
      are examined, suggesting that the challenge of lipid management may be shifting
      from a problem of no treatment to one of undertreatment.

PMID- 14715345
TI  - Effect of abciximab on prothrombin activation and thrombin generation in patients
      with acute myocardial infarction also receiving reteplase.
AB  - Fibrinolysis in acute myocardial infarction activates blood coagulation and may
      favor reocclusion or ischemic complications. The aim of the GUSTO V Italian
      Hematologic Substudy was to compare the effects of full-dose reteplase on
      coagulation activation markers with those of half-dose reteplase combined with
      full-dose abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, during
      the early phase after acute myocardial infarction.

PMID- 14715346
TI  - Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of
      first-time acute myocardial infarction.
AB  - We explored the association between diagnosed rheumatoid arthritis (RA) or
      systemic lupus erythematosus (SLE) and the risk of developing a first-time acute
      myocardial infarction (AMI) by conducting a population-based, case-control
      analysis using data from the United Kingdom-based General Practice Research
      Database (GPRD). Among 8,688 patients with AMI and 33,329 matched controls, the
      adjusted odds ratio (ORs) of AMI for subjects with RA was 1.47 (95% confidence
      interval [CI] 1.23 to 1.76), and in subjects with both RA and diagnosed
      hyperlipidemia, the OR was 7.12 (95% CI 4.16 to 12.18). The risk associated with
      SLE was 2.67 (95% CI 1.34 to 5.34). These results underline that RA and SLE
      increase the risk of AMI.

PMID- 14715347
TI  - Usefulness of compensatory hyperkinesis in the noninfarcted left ventricular wall
      in separating single from multivessel coronary artery disease in patients with
      initial ST-elevation acute myocardial infarction.
AB  - We assessed the contractility of the contralateral wall on 2-dimensional
      echocardiography in 50 patients with an initial ST-elevation acute myocardial
      infarction who underwent coronary angiography. Compensatory hyperkinesis, which
      we defined as a fractional thickening of >/=60% in the contralateral wall, was a
      strong predictor of single-vessel coronary artery disease, with a positive
      predictive value of 85%.

PMID- 14715348
TI  - Relation of thrombomodulin gene polymorphisms to acute myocardial infarction in
      patients <or =50 years of age.
AB  - Full-length sequencing of the thrombomodulin (TM) gene was obtained in 20
      patients with premature acute myocardial infarction (AMI). Clinically relevant
      polymorphisms were identified and further evaluated in 145 patients with
      premature AMI and 143 controls. Despite the fact that TM promoter G-33A and
      C1418T polymorphisms are common in the Chinese population, the association
      between G-33A mutation and premature AMI indicates that we must focus on promoter
      G-33A polymorphism rather than C1418T polymorphism in terms of the role of TM
      gene mutation on premature AMI.

PMID- 14715349
TI  - Temperature of blood in the coronary sinus and right atrium in patients with and
      without coronary artery disease.
AB  - We measured the blood temperature of the coronary sinus and the right atrium in
      control subjects and patients with significant stenoses in the right or left
      coronary arteries. Coronary sinus temperature was increased in patients with
      coronary artery disease compared with the control group and was found to be a
      prognostic factor for mid-term clinical outcome.

PMID- 14715350
TI  - Luminal recovery from six to twelve months after implantation of "thicker strut"
      coronary stents.
AB  - A group of 50 patients with 51 de novo lesions treated with thicker strut stents
      (strut thickness >100 microm) was angiographically evaluated at baseline, after
      stenting, and at 6 and 12 months. Minimal luminal diameter (MLD) significantly
      increased from 6 to 12 months (6 months: 1.72 +/- 0.50 mm vs 12 months: 1.81 +/-
      0.47 mm; p <0.01). The binary restenosis (diameter stenosis >50%) rate was 17% at
      6 months and 11% at 12 months (p = NS). At multivariate analysis, lumen loss at 6
      months (p = 0.018) and deployment pressure (p = 0.041) independently predicted
      the changes in MLD between 6 and 12 months.

PMID- 14715351
TI  - Incidence, predictors, in-hospital, and late outcomes of coronary artery
      perforations.
AB  - We sought to determine the incidence of coronary perforations, predisposing
      factors, and in-hospital and late outcome of patients with coronary perforations.
      Perforations occurred in 0.84% of treated lesions and more frequently in patients
      with complex lesions after atheroablative procedures and who underwent
      intravascular ultrasound guided lumen optimization. The incidence of adverse
      events, emergency coronary artery bypass grafting and death significantly
      decreased over time.

PMID- 14715352
TI  - Effect of simvastatin on serum C-reactive protein during hormone replacement
      therapy.
AB  - Because statins seem to attenuate the early, increased cardiovascular hazard
      induced by hormone replacement therapy (HRT), we treated 16 postmenopausal
      hypercholesterolemic women with coronary artery disease with combined HRT,
      simvastatin, and the combination of HRT and simvastatin in a double-blind,
      crossover, placebo-controlled study; we also evaluated C-reactive protein (CRP)
      levels at the end of each treatment period. We found that only HRT significantly
      increased CRP compared with placebo, whereas the combination of HRT with
      simvastatin did not. We concluded that statins may reduce the inflammatory
      adverse effects associated with the CRP increase induced by HRT.

PMID- 14715353
TI  - Effect of Helicobacter pylori eradication on high-density lipoprotein
      cholesterol.
AB  - We examined the effect of Helicobacter pylori (H. pylori) eradication on lipids
      and apolipoproteins in 87 patients with duodenal ulcers. A significant increase
      was observed in high-density lipoprotein (HDL) cholesterol (+24.7%, p <0.001),
      apolipoprotein AI (+9.0%, p <0.001), and apolipoprotein AII (+11.7%, p <0.001)
      after eradication. Minor increases occurred in total cholesterol, triglycerides,
      and apolipoprotein B, whereas low-density lipoprotein cholesterol remained
      unchanged. Our results suggest that chronic H. pylori infection reduces plasma
      levels of HDL cholesterol and that eradication improves the lipoprotein pattern.

PMID- 14715354
TI  - Effect of physical activity on serum C-reactive protein.
AB  - This study examines the association between physical activity and C-reactive
      protein levels, indicating that high levels of strenuous aerobic activity are
      associated with lower C-reactive protein levels among men.

PMID- 14715355
TI  - Comparison of catecholamine response during tilt-table-induced vasovagal syncope
      in patients <35 to those >65 years of age.
AB  - This study compared alterations in arterial catecholamine concentrations
      associated with tilt-induced vasovagal syncope that differed in older (>65 years)
      and younger patients (<35 years). Older patients with tilt-positive tests tended
      to exhibit higher baseline epinephrine (E) concentrations and lesser E surge
      before development of syncope than younger patients (<35 years), whereas both
      groups manifested comparable norepinephrine (NE) responsiveness.

PMID- 14715356
TI  - Usefulness of brain natriuretic peptide as a marker for separating cardiac and
      noncardiac causes of syncope.
AB  - We retrospectively evaluated the feasibility of measuring brain natriuretic
      peptide to identify cardiac syncope in 148 consecutive patients with syncope.
      Sixty-one patients with cardiac syncope were identified. A cut-off value of 40
      pg/ml was used to determine the cardiac causes of syncope; the sensitivity and
      specificity for identification of cardiac syncope were 82% and 92%, respectively.
      Thus, measurement of brain natriuretic peptide concentrations may help confirm
      cardiac causes of syncope, and merits consideration for incorporation into the
      algorithm used to diagnose syncope.

PMID- 14715357
TI  - A novel form of familial bidirectional ventricular tachycardia.
AB  - We evaluated a family with 30 members, 3 of whom had incessant polymorphous and
      bidirectional ventricular tachycardia (VT) that was electrocardiographically
      similar to that described in other familial polymorphic VT series; the VT was
      unrelated to exercise and asymptomatic. More subtle, but morphologically similar,
      ventricular arrhythmias were detected in 3 other family members. Genes related to
      intracellular calcium transport were specifically excluded.

PMID- 14715358
TI  - Development of a depressed left ventricular ejection fraction in patients with
      left ventricular hypertrophy and a normal ejection fraction.
AB  - The progression from concentric left ventricular (LV) hypertrophy to heart
      failure has not been well defined. Of 159 predominantly hypertensive African
      American patients with LV hypertrophy and a normal ejection fraction (EF), 28
      (18%) developed a reduced EF after a median follow-up of approximately 4 years.
      Risk factors for this outcome included a history of coronary artery disease,
      pulmonary edema seen on a chest x-ray, or a subsequent myocardial infarction.

PMID- 14715359
TI  - Comparison of effects on left ventricular filling pressure of intravenous
      nesiritide and high-dose nitroglycerin in patients with decompensated heart
      failure.
AB  - The results of this study showed an advantage of nesiritide compared with high
      dose nitroglycerin in the treatment of patients with decompensated heart failure.
      Nesiritide resulted in an early decrease in pulmonary capillary wedge pressure (<
      or =15 minutes), which was sustained throughout the study period (24 hours)
      without the need for up-titration. In contrast, the onset of the nitroglycerin
      mediated hemodynamic effect was delayed, and despite aggressive up-titration, the
      decrease in pulmonary capillary wedge pressure was gradually attenuated because
      of the early development of tolerance.

PMID- 14715360
TI  - Meta-Analysis of effectiveness or lack thereof of angiotensin-converting enzyme
      inhibitors for prevention of heart failure in patients with systemic
      hypertension.
AB  - We undertook a meta-analysis of large, randomized controlled trials in
      hypertensive subjects that compared angiotensin-converting enzyme (ACE)
      inhibitors with different classes of antihypertensive drugs. Compared with
      subjects randomized to drugs different from ACE inhibitors, those treated with
      ACE inhibitors did not show a different risk of congestive heart failure (CHF)
      (odds ratio 1.03, 95% confidence interval 0.96 to 1.12, p = 0.407). The degree of
      protection from CHF associated with the use of ACE inhibitors showed a
      nonsignificant trend to increase with age and the degree of blood pressure
      control. Thus, the hypothesis that ACE inhibitors are superior to other
      antihypertensive drugs for prevention of CHF in hypertension remains unproven.

PMID- 14715361
TI  - Prevalence of QRS prolongation in a community hospital cohort of patients with
      heart failure and its relation to left ventricular systolic dysfunction.
AB  - Adverse outcomes in heart failure occur more frequently with QRS prolongation.
      The results of our study have shown that 1/4 of community hospital patients with
      heart failure of sufficient severity leading to hospitalization have a QRS
      duration of > or =120 ms and that this degree of QRS prolongation is associated
      with substantially more severe left ventricular (LV) systolic dysfunction, LV
      dilation, and mitral regurgitation.

PMID- 14715362
TI  - Comparison of efficacy, safety, and cost of low-molecular-weight heparin with
      continuous-infusion unfractionated heparin for initiation of anticoagulation
      after mechanical prosthetic valve implantation.
AB  - We compared the efficacy, safety, and impact on postoperative hospital length of
      stay and inpatient hospital costs of low-molecular-weight heparin with that of
      unfractionated heparin as a "bridge" to achieving therapeutic levels of
      anticoagulation with warfarin in patients with newly implanted prosthetic heart
      valves. The patients who received low-molecular-weight heparin had a shorter
      length of stay and decreased postoperative costs compared with the control
      subjects receiving unfractionated heparin.

PMID- 14715363
TI  - Prognostic usefulness of echocardiographic dobutamine in younger (14 to 25 years)
      and older (40 to 55 years) patients with idiopathic dilated cardiomyopathy.
AB  - We studied 16 younger patients (<25 years old) and 16 older patients (>40 years
      old) to investigate the prognostic value of echocardiographic dobutamine-induced
      changes. The results of this study showed that although the percent achieved of
      predicted oxygen consumption was lower in the younger group, no prognostic
      information was given regarding the outcome of this particular group. In
      contrast, echocardiographic dobutamine-induced changes can distinguish high-risk
      younger patients.

PMID- 14715365
TI  - A prospective registry of 5,451 patients with ultrasound-confirmed deep vein
      thrombosis.
AB  - We enrolled 5,451 patients with ultrasound-confirmed deep vein thrombosis (DVT),
      including 2,892 women and 2,559 men, from 183 United States sites in our
      prospective registry. The 5 most frequent co-morbidities were hypertension (50%),
      surgery within 3 months (38%), immobility within 30 days (34%), cancer (32%), and
      obesity (27%). Of the 2,726 patients who had their DVT diagnosed while in the
      hospital, only 1,147 (42%) received prophylaxis within 30 days before diagnosis.

PMID- 14715364
TI  - Left ventricular diastolic dysfunction in Ebstein's anomaly.
AB  - This study was performed to evaluate left ventricular (LV) diastolic function in
      patients with Ebstein's anomaly using Doppler echocardiography. We found that LV
      abnormal relaxation in this anomaly cannot be explained by right ventricular
      volume overload alone. Furthermore, LV diastolic dysfunction persists even after
      intracardiac repair.

PMID- 14715366
TI  - Prevalence of increased cardiac troponin I levels in patients with and without
      acute pulmonary embolism and relation of increased cardiac troponin I levels with
      in-hospital mortality in patients with acute pulmonary embolism.
AB  - Cardiac troponin I levels were increased in 24 of 147 patients (16%) with
      documented acute pulmonary embolism and in 20 of 594 patients (3%) without
      pulmonary embolism (p <0.001). In patients with acute pulmonary embolisms, 8 of
      24 (33%) with increased cardiac troponin I levels and 9 of 123 (7%) with normal
      cardiac troponin I levels died during hospitalization (p <0.001).

PMID- 14715367
TI  - Effect of cold, isometric exercise, and combination of both on aortic pulse in
      healthy subjects.
AB  - The aortic pulse-wave velocity (PWV) and augmentation index were measured in 24
      healthy adults at baseline, during a cold pressor test (CPT), during hand-grip
      isometric exercise test (HIE), and during a combination of CPT plus HIE. The PWV
      and augmentation index increased significantly during CPT and HIE compared with
      baseline (p <0.01). The combined effect of CPT and HIE on PWV and augmentation
      index was greater compared with the effect of each intervention alone.

PMID- 14715368
TI  - Prevalence of stroke and associated risk factors in Asian Indians living in the
      state of Georgia, United States of America.
AB  - This study is the first attempt to assess the prevalence of stroke and associated
      risk factors in Asian Indians living in the United States. The overall prevalence
      of stroke is 2.77% (men 3.72% and women 1.77%). Stroke was significantly
      associated with systemic hypertension, diabetes mellitus, coronary artery
      disease, end-stage renal disease, and family history of stroke and myocardial
      infarction.

PMID- 14715369
TI  - Usefulness of ambulatory electrocardiographic monitoring for myocardial ischemia
      after coronary bypass.
AB  - Cardiac patients with asymptomatic myocardial ischemia have a poor prognosis.
      Ambulatory electrocardiographic monitoring can help to ensure that these
      patients, who are unaware of their high-risk status, are relieved of residual
      myocardial ischemia in response to cardioprotective medication, and rendered as
      low cardiac risk.

PMID- 14715370
TI  - Chest pain in an adult with truncus arteriosus communis.
AB  - We present a case of an adult patient with truncus arteriosus communis and
      secondary pulmonary hypertension. He had chest pain and sudden death due to
      cardiac tamponade caused by intramural-limited dissection and rupture of the
      common trunk.

PMID- 14715371
TI  - The metabolic syndrome.

PMID- 14715372
TI  - Identification of naturally occurring spirostenols preventing beta-amyloid
      induced neurotoxicity.
AB  - 22R-Hydroxycholesterol is an intermediate in the steroid biosynthesis pathway
      shown to exhibit a neuroprotective property against beta-amyloid (1-42) (Abeta)
      toxicity in rat PCl2 and human NT2N neuronal cells by binding and inactivating
      Abeta. In search of potent 22R-hydroxycholesterol derivatives, we assessed the
      ability of a series of naturally occurring entities containing the 22R
      hydroxycholesterol structure to protect PC12 cells against Abeta-induced
      neurotoxicity, determined by measuring changes in membrane potential,
      mitochondrial diaphorase activity, ATP levels and trypan blue uptake. 22R
      Hydroxycholesterol derivatives sharing a common spirost-5-en-3-ol or a furost-5
      en-3-ol structure were tested. Although some of these compounds were
      neuroprotective against 0.1 microM Abeta, only three protected against the 1-10
      microM Abeta-induced toxicity and, in contrast to 22R-hydroxycholesterol, all
      were devoid of steroidogenic activity. These entities shared a common structural
      feature, a long chain ester in position 3 and common stereochemistry. The
      neuroprotective property of these compounds was coupled to their ability to
      displace radiolabeled 22R-hydroxycholesterol from Abeta, suggesting that the
      Abeta-22R-hydroxycholesterol physicochemical interaction contributes to their
      beneficial effect. In addition, a 22R-hydroxycholesterol derivative inhibited the
      formation of neurotoxic amyloid-derived diffusible ligands. Computational docking
      simulations of 22R-hydroxycholesterol and its derivatives on Abeta identified two
      binding sites. Chemical entities, as 22R-hydroxycholesterol, seem to bind
      preferentially only to one site. In contrast, the presence of the ester chain
      seems to confer the ability to bind to both sites on Abeta, leading to
      neuroprotection against high concentrations of Abeta. In conclusion, these
      results suggest that spirost-5-en-3-ol naturally occurring derivatives of 22R
      hydroxycholesterol might offer a new approach for Alzheimer's disease therapy.

PMID- 14715373
TI  - Are the 11-oxo-steroids really so hindered towards organometallic compounds?
AB  - Allylation of an 11-oxo-steroid, the protected adrenosterone, was studied to
      examine more closely the steric hindrance of such a ketosteroid. While the beta
      face exhibits, as well known, a strong steric hindrance, the alpha side appears
      to be only relatively hindered. A high diastereoselectivity was observed in the
      addition of crotyl magnesium bromide.

PMID- 14715374
TI  - Isolation and structure elucidation of the major photodegradation products of
      loteprednol etabonate.
AB  - Photodegradation of loteprednol etabonate (5), a steroid anti-inflammatory drug,
      in the solid state, in aqueous suspension, and in aqueous acetonitrile solution
      has been investigated. Analysis by HPLC showed that the profile of
      photodegradation products in the solid state was qualitatively similar to that in
      the aqueous suspension, although the profile in the aqueous acetonitrile solution
      was considerably different. The major photodegradation products were isolated
      from the aqueous suspension and the aqueous acetonitrile solution by using
      preparative reversed-phase HPLC and their structures were elucidated on the basis
      of spectroscopic data. Photolysis in the solid state and in aqueous suspension
      yielded three rearrangement products, chloromethyl 17alpha-ethoxycarbonyloxy
      11beta-hydroxy-5alpha-methyl-2-oxo-19-norandrosta-1(10),3-diene-17beta
      carboxylate (8), chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-1-methyl-3
      oxo-6(5-->10alpha)-abeo-19-norandrosta-1,4-diene-17beta-carboxylate (9), and
      chloromethyl 1beta,11beta-epoxy-17alpha-ethoxycarbonyloxy-2-oxo-10alpha-androsta
      4-ene-17beta-carboxylate (10). In aqueous acetonitrile solution, 10 was the major
      product, however, 8 and 9 were not obtained. Pathways for the formation of these
      compounds from loteprednol etabonate (5) are proposed.

PMID- 14715375
TI  - Stereoselective reactions of (20R)-3,20-dihydroxy-(3',4'-dihydro-2'H-pyranyl)-5
      pregnene derivatives form 27-nor-3,20,23,26-tetrahydroxy-cholesten-22-ones and
      related bromo ketones.
AB  - The previously reported analog of pregnenolone having a 3,4-dihydro-2H-pyran
      attached via a Cz.sbnd;C bond to the C-20 position (1), stereoselectively reacts
      with m-chloroperoxybenzoic acid in methanol at -5 degrees C. Acid-catalyzed
      hydrolysis of the isolated intermediates gives good yields of mostly a new 27
      norcholesterol analog: (20R,23R)-3,20,23,26-tetrahydroxy-27-norcholest-5-en-22
      one-3-acetate (2a, and a smaller amount of its 23S enantiomer 2b). Three
      different conditions of epoxidation and methanolysis followed by acid-catalyzed
      hydrolysis typically produce approximately 2:1 ratios of the 23R:23S
      diastereoisomers with a C-23 hydroxy group at the new asymmetric center. Bromine
      also reacts stereoselectively with (20R)-3,20-dihydroxy-(3',4'-dihydro-2'H
      pyranyl)-5-pregnene (4) giving mostly (20R,23R)-23-bromo-3,20,26-trihydroxy-27
      norcholest-5-en-22-one (7a). Thus both major steroidal products 2a and 7a have
      the same C-23R configuration. Assignment of molecular structures and the absolute
      configurations to 1 and 2a were based on elemental analysis, mass spectra,
      nuclear magnetic resonance, FTIR infrared spectroscopic analysis and X-ray
      crystallography. Mechanisms are discussed for stereochemical selectivity during
      epoxidation and bromination of the 3,4-dihydro-2H-pyranyl ring in 1 and 4.

PMID- 14715376
TI  - Gradient enhanced selective experiments in the 1H NMR chemical shift assignment
      of the skeleton and side-chain resonances of stigmasterol, a phytosterol
      derivative.
AB  - The applicability of homonuclear gradient enhanced NMR experiments is
      demonstrated in the structure determination of steroid derivatives using
      stigmasterol as a model compound. High resolution 1H NMR spectra of steroids very
      often display well resolved multiplets usually in the low-field region, and these
      signals can be used as starting points in several selective NMR experiments to
      study scalar (J coupling), and dipolar (NOE) interactions. Selective excitation
      was carried out using a double pulsed-field gradient spin-echo sequence (DPFGSE)
      in which 180 degrees Gaussian pulses are sandwiched between sine shaped z
      gradients. Scalar interactions were studied by homonuclear DPFGSE-COSY, DPFGSE
      relay-COSY and DPFGSE-TOCSY experiments, while DPFGSE-NOESY was used to monitor
      spatial environment of the selectively excited proton. These methods provided
      unambiguous assignments for signals of the main skeleton and the side-chain of
      the steroid molecule. In addition, they allowed determination of the
      conformationally important homonuclear proton-proton coupling constants (J).

PMID- 14715377
TI  - The implications of 7-dehydrosterol-7-reductase deficiency (Smith-Lemli-Opitz
      syndrome) to neurosteroid production.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple
      malformation/mental retardation syndrome with an estimated incidence among
      individuals of European ancestry of 1 in 20000 to 1 in 30000. It is caused by
      inactivity of the enzyme 7-dehydrosterol-delta(7)-reductase, which catalyses the
      terminal transformation in cholesterol synthesis. Patients show not only an
      increased level of 7-dehydrocholesterol in blood and tissues, but also increased
      8-dehydrocholesterol because of the presence of an active delta(8)-delta(7)
      isomerase. A major consequence of these biochemical abnormalities is the
      alteration of normal embryonic and fetal somatic development causing postnatal
      abnormalities of growth, learning, language and behavior. While deficient
      cholesterol during early development is the primary cause of central nervous
      system (CNS) abnormalities and retardation, we questioned whether neurosteroids
      could also be involved since they can have a profound influence on behavioral
      characteristics. Disordered neurosteroidogenesis would be expected in SLOS and
      could be caused by a deficiency in classical neurosteroid synthesis secondary to
      cholesterol deficiency, or by synthesis from 7- and 8-dehydrocholesterol of novel
      neurosteroids with delta(7) or delta(8) unsaturation which may have altered
      activity compared with conventional neurosteroids. In particular we sought
      analogues of dehydroepiandrosterone sulfate, pregnenolone sulfate and the
      pregnanolone epimers. We targeted urine from post-pubertal females, as this type
      of sample would be most likely to yield identifiable amounts of the pregnanolone
      metabolites of progesterone. Analysis by GC/MS of urinary steroids excreted by
      post-pubertal females confirmed the presence of neurosteroid-like compounds in
      SLOS patient's urine. Even though the new neuroactive steroids identified were
      unlikely to have been formed in the brain, it is likely that mechanisms for their
      synthesis are operable in this organ.

PMID- 14715378
TI  - Chemical synthesis of two novel diaryl ether dimers of estradiol-17beta.
AB  - We recently detected the formation of estradiol-17beta (estradiol) dimers, linked
      together through a diaryl ether bond between the C-3 phenolic oxygen of one
      estradiol molecule and the 2- or 4-position aromatic carbon of another estradiol,
      following incubations of [3H]estradiol with human liver microsomes or cytochrome
      p450 enzymes in the presence of NADPH. Using estradiol as the starting material,
      we designed a four-step method for the chemical synthesis of these two estrogen
      dimers with the Ullmann condensation reaction as a key step. Step 1: Synthesis of
      2- or 4-bromoestradiol from estradiol. Step 2: Protection of the C-3 phenolic
      hydroxyl group of the 2- or 4-bromoestradiol. Step 3: The Ullmann condensation
      reaction between the phenol-protected bromoestradiol and the estradiol potassium
      salt under our modified reaction conditions (with a 41% product yield). Step 4:
      Removal of the C-3 benzyl group by catalytic hydrogenation. The chromatographic
      and various spectrometric properties of the two synthesized compounds were
      identical to those metabolically formed by human cytochrome p450 3A4.

PMID- 14715379
TI  - Within-person variability of urinary 6beta-hydroxycortisol to urinaryl ratios in
      Caucasian women.
AB  - Cortisol is metabolized to 6beta-hydroxycortisol by human cytochrome p450-3A4
      (CYP3A4), an important enzyme involved in the metabolism of a variety of
      exogenous and endogenous compounds. Both cortisol and 6beta-hydroxycortisol are
      excreted in urine, and the ratio of these steroids has been proposed as an
      indicator of CYP3A4 activity. We evaluated within-person variability of this
      biomarker in 10 healthy Caucasian women, aged 23-58 years. Each study participant
      was asked to provide a fasting morning urine sample once a week consecutively for
      8 weeks. Urinary cortisol and 6beta-hydroxycortisol were determined by
      immunoassay kits purchased from the DiaSorin (Stillwater, MN) and the Stabiligen
      (Nancy, France), respectively. The coefficients of variation (CV) of urinary
      6beta-hydroxycortisol to cortisol ratios from study participants ranged from 16.7
      to 51.4% (mean, 31.1%) over the study period. The level of the ratio measured in
      any single urine sample was correlated reasonably well with the average of the
      ratios over the 8-week study period from the same woman, with the mean
      correlation coefficient of 0.79. These results indicated that urinary 6beta
      hydroxycortisol to cortisol ratios measured in a spot urine sample may reflect
      the level of this biomarker over a relatively longer time period in Caucasian
      women, and thus, it can be used in epidemiologic studies as a biomarker to
      evaluate the association between CYP3A4 activity and disease risk.

PMID- 14715380
TI  - Binding characteristics of [3H]delta(5)-androstene-3beta,17beta-diol to a nuclear
      protein in the rabbit vagina.
AB  - In this study, we investigated the binding characteristics of [3H]Delta(5)
      androstene-3beta,17beta-diol to rabbit vaginal cytosolic and nuclear extracts and
      in freshly excised intact tissue strips. [3H]delta(5)-Androstene-3beta,17beta
      diol bound to a protein(s) in the vaginal nuclear extract with high affinity
      (K(d)=3-5 nM) and limited capacity (50-100 fmol/mg protein). No specific binding
      was detected in the cytoplasmic extracts. Competitive binding studies showed that
      binding of [3H]delta(5)-androstene-3beta,17beta-diol was effectively displaced
      with unlabeled delta(5)-androstene-3beta,17beta-diol but not with
      dehydroepiandrosterone, testosterone, dihydrotestosterone, triamcinolone
      acetonide, or progesterone. However, estradiol at high concentrations partially
      displaced bound [3H]delta(5)-androstene-3beta,17beta-diol. Incubation of freshly
      excised vaginal tissue strips with [3H]delta(5)-androstene-3beta,17beta-diol in
      the absence or presence of excess unlabeled delta(5)-androstene-3beta,17beta-diol
      for 1h at 37 degrees C resulted in specific binding to a soluble macromolecule in
      the nuclear KCl extracts. In addition, quantitative measurement of estrogen
      receptor, androgen receptor and delta(5)-androstene-3beta,17beta-diol binding
      protein was performed by equilibrium ligand binding assays using extracts of
      distal vaginal tissue from intact animals or ovariectomized animals treated for 2
      weeks with vehicle, estradiol, testosterone, or estradiol plus testosterone.
      These changes in steroid hormone levels resulted in opposing trends between the
      estrogen receptor and delta(5)-androstene-3beta,17beta-diol binding protein,
      suggesting that delta(5)-androstene-3beta,17beta-diol binding protein is
      regulated differently by the hormonal milieu than the estrogen receptor. These
      data suggest that rabbit vaginal tissue expresses a novel binding protein which
      specifically binds delta(5)-androstene-3beta,17beta-diol and is distinct from the
      androgen and estrogen receptors.

PMID- 14715381
TI  - Quality improvement challenges in pain management.

PMID- 14715382
TI  - Social communication of pain enhances protective functions: a comment on Deyo,
      Prkachin and Mercer (2004).

PMID- 14715383
TI  - Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury
      and in fibromyalgia.
AB  - Patients with chronic pain after whiplash injury and fibromyalgia patients
      display exaggerated pain after sensory stimulation. Because evident tissue damage
      is usually lacking, this exaggerated pain perception could be explained by
      hyperexcitability of the central nervous system. The nociceptive withdrawal
      reflex (a spinal reflex) may be used to study the excitability state of spinal
      cord neurons. We tested the hypothesis that patients with chronic whiplash pain
      and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord
      hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22)
      and healthy controls (n=29). Two types of transcutaneous electrical stimulation
      of the sural nerve were applied: single stimulus and five repeated stimuli at 2
      Hz. Electromyography was recorded from the biceps femoris muscle. The main
      outcome measurement was the minimum current intensity eliciting a spinal reflex
      (reflex threshold). Reflex thresholds were significantly lower in the whiplash
      compared with the control group, after both single (P=0.024) and repeated
      (P=0.035) stimulation. The same was observed for the fibromyalgia group, after
      both stimulation modalities (P=0.001 and 0.046, respectively). We provide
      evidence for spinal cord hyperexcitability in patients with chronic pain after
      whiplash injury and in fibromyalgia patients. This can cause exaggerated pain
      following low intensity nociceptive or innocuous peripheral stimulation. Spinal
      hypersensitivity may explain, at least in part, pain in the absence of detectable
      tissue damage.

PMID- 14715384
TI  - Development of sensitivity to facial expression of pain.
AB  - The ability to perceive pain in others is an important human capacity. Its
      development has not been studied. The present study examined the development of
      sensitivity to evidence of pain from childhood to early adulthood. One hundred
      and thirty-four males and females from four age groups (5-6, 8-9, 11-12 years and
      young adult) took part. They judged the amount of pain displayed on videotaped
      excerpts of the facial expressions of pain patients. Excerpts were selected to
      display no pain, some pain and strong pain, based on facial measurements, and
      were displayed to participants in a signal-detection paradigm. All participant
      groups were more sensitive to evidence of strong than some pain. The ability to
      detect pain expressions increased across the young, middle and older groups of
      children, but older children did not differ from adults. Increasing age was
      generally associated with increasing sensitivity to more subtle facial signs of
      pain. The results indicate that the ability to perceive pain in others is already
      significantly developed by the ages of five to six, but refinements in the
      ability continue through to early adulthood. These findings represent the first
      description of the development of the ability to perceive pain in others.
      Important areas for future research into the neurobiological, personal and social
      determinants of this ability are highlighted.

PMID- 14715385
TI  - Cholinergic modulation of nociceptive responses in vivo and neuropeptide release
      in vitro at the level of the primary sensory neuron.
AB  - Muscarinic acetylcholine receptors (mAChRs) have been widely reported as
      pharmacological targets for the treatment of pain. However, most of these efforts
      have focused on CNS mAChRs and their role in modulating nociception at the level
      of the spinal cord. The present study examines the contribution of peripheral
      mAChRs in trigeminal nociceptive pathways using a combination of in vivo and in
      vitro approaches. In the formalin model of orofacial nociception in rats, a peri
      oral co-injection of the M2 agonist arecaidine dose-dependently inhibited phase 2
      nocifensive behavior up to approximately 50% at 5 nmol. This effect was blocked
      by co-treatment with the mAChR antagonist atropine and was not seen when
      arecaidine was administered under the skin of the back, a site distant from that
      of the formalin injection. In vitro superfusion of isolated rat buccal mucosa
      with the non-selective mAChR agonist muscarine or arecaidine led to a
      concentration-dependent inhibition of capsaicin-evoked CGRP release to 39%
      (EC50=255 nM) and 28% (EC50=847 nM) of control values, respectively. Both
      responses were blocked by the non-selective mAChR antagonist atropine or the M2
      antagonist gallamine. Further, the endogenous ligand ACh produced a bi-phasic
      response, potentiating evoked CGRP release to 195% of control (EC50= 918nM) and
      inhibiting evoked CGRP release to 45% of control (EC50=255 microM), effects that
      were shown to be mediated by nAChRs and mAChRs, respectively. Finally, combined
      in situ hybridization/immunofluorescence demonstrated that m2 mRNA was present in
      20% of trigeminal ganglion neurons between 30 and 60 microm in diameter and that
      5-9% of these also expressed CGRP or VR1 immunoreactivity. These results show
      that activation of peripheral M2 receptors produces antinociception in vivo and
      the inhibition of nociceptor activity in vitro. While histological analyses at
      the level of the trigeminal neuronal cell bodies leave open the question of
      whether the effects of M2 agonists are direct or indirect, these data indicate
      that primary sensory neuronal M2 receptors may represent a viable peripheral
      target for the treatment of pain and inflammation.

PMID- 14715386
TI  - Anti-hyperalgesic activity of the cox-2 inhibitor lumiracoxib in a model of bone
      cancer pain in the rat.
AB  - Chronic pain resulting from metastatic bone cancer remains poorly understood and
      resistant to treatment. Here we have examined the effect of the novel COX-2
      enzyme inhibitor lumiracoxib in a model of bone cancer pain in the rat.
      Lumiracoxib was administered orally twice daily from day 10 to day 20 after
      injection of MRMT-1 tumour cells into one tibia. Mechanical hyperalgesia,
      measured as the reduction in weight-bearing of the ipsilateral limb, and the
      development of static and dynamic allodynia were significantly inhibited by
      repeated lumaricoxib administration. A similar reduction in hyperalgesia and
      allodynia was noted after twice daily administration of another COX-2 inhibitor,
      valdecoxib, whilst a single acute administration of either drug on day 20,
      produced no anti-nociceptive activity. Bone mineral density measurements,
      radiological scores and histological analysis showed that chronic lumaricoxib
      treatment also significantly attenuated bone destruction induced by tumour cell
      injection. These data indicate that lumiracoxib and other COX-2 inhibitors have
      potential therapeutic benefit in the treatment of bone cancer pain.

PMID- 14715387
TI  - Addition of ultralow dose naloxone to postoperative morphine PCA: unchanged
      analgesia and opioid requirement but decreased incidence of opioid side effects.
AB  - Ultralow doses of naloxone (0.001-0.1 microg/kg) produce analgesia in animal
      models. However, no clinical study has evaluated the combination of ultralow dose
      naloxone and morphine using patient-controlled analgesia (PCA). This randomized,
      double blind controlled study sought to determine if the combination of ultralow
      dose naloxone and morphine in PCA solutions affects opioid requirements,
      analgesia, and side effects. Two-hundred and sixty-five patients (18-65 years
      old) undergoing operations were randomized to receive PCA morphine 1 mg/ml
      (n=129) or PCA morphine 1 mg/ml plus naloxone 0.6 microg/ml (n=136). We evaluated
      the numbers of supplemental rescue doses, the cumulative dose of each PCA
      solution, pain intensity, pain relief, and opioid side effects during the first
      24 h after surgery. We found that opioid requirements did not differ
      significantly between groups. The morphine+naloxone group on average required
      0.07 mg more morphine (95% CI -1.1 to 1.3) during the 24 h than the morphine
      group. Pain intensity levels were also similar in both groups. The
      morphine+naloxone group had 0.06 units lower (95% CI -0.5 to 0.4) pain intensity
      levels than the morphine group. The morphine+naloxone group had a lower incidence
      of nausea and pruritus than the morphine group (P=0.01 for both symptoms).
      However, the incidence of vomiting, time to tolerate fluids, sedation, and
      urinary retention were similar between groups (all P values >0.1). The
      combination of ultralow dose naloxone and morphine in PCA does not affect
      analgesia or opioid requirements, but it decreases the incidence of nausea and
      pruritus.

PMID- 14715388
TI  - Vulvar vestibulitis severity--assessment by sensory and pain testing modalities.
AB  - Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre
      menopausal women. Previous quantitative sensory test (QST) studies have
      demonstrated reduced vestibular pain thresholds in these patients. Here we try to
      find whether QST findings correlate to disease severity. Thirty-five vestibulitis
      patients, 17 with moderate and 18 with severe disorder, were compared to 22 age
      matched control women. Tactile and pain thresholds for mechanical pressure and
      thermal pain were measured at the posterior fourcette. Magnitude estimation of
      supra-threshold painful stimuli were obtained for mechanical and thermal stimuli,
      the latter were of tonic and phasic types. Pain thresholds were lower and supra
      threshold magnitude estimations were higher in VVS patients, in agreement with
      disease severity. Cut-off points were defined for results of each test,
      discriminating between moderate VVS, severe VVS and healthy controls, and
      allowing calculation of sensitivity and specificity of the various tests. Our
      findings show that the best discriminative test was mechanical pain threshold
      obtained by a simple custom made 'spring pressure device'. This test had the
      highest kappa value (0.82), predicting correctly 88% of all VVS cases and 100% of
      the severe VVS cases. Supra-threshold pain magnitude estimation for tonic heat
      stimulation also had a high kappa value (0.73) predicting correctly 82% overall
      with a 100% correct diagnosis of the control group. QST techniques, both
      threshold and supra-threshold measurements, seem to be capable of discriminating
      level of severity of this clinical pain syndrome.

PMID- 14715389
TI  - Chronic back pain and major depression in the general Canadian population.
AB  - Chronic pain and depression are two of the most common health problems that
      health professionals encounter, yet only a handful of epidemiological studies
      have investigated the relationship between these conditions in the general
      population. In the present study we examined the prevalence and correlates of
      major depression in persons with chronic back pain using data from the first
      cycle of Canadian Community Health Survey in a sample of 118,533 household
      residents. The prevalence of chronic back pain was estimated at 9% of persons 12
      years and older. Rates of major depression, determined by the short-form of the
      Composite International Diagnostic Interview, were estimated at 5.9% for pain
      free individuals and 19.8% for persons with chronic back pain. The rate of major
      depression increased in a linear fashion with greater pain severity. In logistic
      regression models, back pain emerged as the strongest predictor of major
      depression after adjusting for possible confounding factors such as demographics
      and medical co-morbidity. The combination of chronic back pain and major
      depression was associated with greater disability than either condition alone,
      although pain severity was found to be the strongest overall predictor of
      disability.

PMID- 14715390
TI  - Understanding recall of weekly pain from a momentary assessment perspective:
      absolute agreement, between- and within-person consistency, and judged change in
      weekly pain.
AB  - To better understand the association between pain recalled over a previous week
      and the average of multiple momentary reports of pain taken during the same
      period, 68 patients with chronic pain completed both weekly recall and momentary
      reports over a 2-week period and assessed their change in pain over the 2 weeks.
      Pearson correlations and intraclass correlation coefficients were computed to
      index three different ways of comparing the measures on both a between-person and
      within-person basis. Between-person correspondence between weekly and momentary
      reports was generally moderate to high, but within-person correspondence was low.
      Judged change was only weakly related to changes over a week computed from weekly
      recall or from average momentary reports. Given the importance of within-person
      change for treatment studies, these results indicate a serious nonequivalence in
      weekly recall and averaged momentary reports of pain.

PMID- 14715391
TI  - Disengagement from pain: the role of catastrophic thinking about pain.
AB  - This paper reports an experimental investigation of attentional engagement to and
      disengagement from pain. Thirty-seven pain-free volunteers performed a cueing
      task in which they were instructed to respond to visual target stimuli, i.e. the
      words 'pain' and 'tone'. Targets were preceded by pain stimuli or tone stimuli as
      cues. Participants were characterized as high or low pain catastrophizers, using
      self-reports. We found that the effect of cueing upon target detection was
      differential for high and low pain catastrophizers. Analyses revealed a similar
      amount of attentional engagement to pain in both groups. However, we also found
      that participants high in pain catastrophizing had difficulty disengaging from
      pain, whereas participants low in pain catastrophizing showed no retarded
      disengagement from pain. Our results provide further evidence that catastrophic
      thinking enhances the attentional demand of pain, particularly resulting in
      difficulty disengaging from pain. The clinical implications of these findings are
      discussed.

PMID- 14715392
TI  - Psychosocial factors predictive of occupational low back disability: towards
      development of a return-to-work model.
AB  - This paper focuses on the identification and testing of potential psychosocial
      factors contributing to an integrated multivariate predictive model of
      occupational low back disability. Psychosocial predictors originate from five
      traditions of psychosocial research: psychopathological, cognitive, diathesis
      stress, human adaptation and organizational psychology. The psychosocial
      variables chosen for this study reflect a full range of research findings. They
      were investigated using 253 subacute and chronic pain injured workers. Three
      outcome measures were utilized: return-to-work status, duration of disability and
      disability costs. The key psychosocial predictors identified were expectations of
      recovery and perception of health change. Also implicated, but to a lesser
      degree, were occupational stability, skill discretion at work, co-worker support,
      and the response of the workers' compensation system and employer to the
      disability. All psychosocial models were better at predicting who will return
      than who will not return to work.

PMID- 14715393
TI  - Pain and analgesic response after third molar extraction and other postsurgical
      pain.
AB  - There is uncertainty over whether the patient group in which acute pain studies
      are conducted (pain model) has any influence on the estimate of analgesic
      efficacy. Data from four recently updated systematic reviews of aspirin 600/650
      mg, paracetamol 600/650 mg, paracetamol 1000 mg and ibuprofen 400 mg were used to
      investigate the influence of pain model. Area under the pain relief versus time
      curve equivalent to at least 50% maximum pain relief over 6 h was used as the
      outcome measure. Event rates with treatment and placebo, and relative benefit
      (RB) and number needed to treat (NNT) were used as outputs from the meta
      analyses. The event rate with placebo was systematically statistically lower for
      dental than postsurgical pain for all four treatments. Event rates with
      analgesics, RB and NNT were infrequently different between the pain models.
      Systematic difference in the estimate of analgesic efficacy between dental and
      postsurgical pain models remains unproven, and, on balance, no major difference
      is likely.

PMID- 14715394
TI  - Movements modulate cortical activities evoked by noxious stimulation.
AB  - To evaluate the effects of movement on cortical activities evoked by noxious
      stimulation, we recorded magnetoencephalography following noxious YAG laser
      stimulation applied to the dorsum of the left hand in normal volunteers. Results
      of the present study can be summarized as follows: (1) active movement of the
      hand ipsilateral to the side of noxious stimulation resulted in significant
      attenuation of both primary and secondary somatosensory cortices (SI and SII) in
      the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in
      the hemisphere ipsilateral to the side of stimulation (iSII) was not affected.
      (2) Active movement of the hand contralateral to the side of noxious stimulation
      resulted in significant attenuation of cSII. Activity in cSI and iSII was not
      affected. (3) Passive movement of the hand ipsilateral to the side of noxious
      stimulation resulted in significant attenuation of cSI. Activity in cSII and iSII
      was not affected. (4) Visual analogue scale (VAS) changes showed a similar
      pattern to the amplitude changes of cSII. These results suggest that activities
      in three regions are modulated by movements differently. Inhibition in cSI was
      considered to be mainly due to an interaction in SI by the signals ascending from
      the stimulated and movement hand. Inhibition in cSII was considered to be mainly
      due to particular brain activities relating to motor execution and/or movement
      execution associated with a specific attention effect. In addition, since VAS
      changes showed a similar relationship with the amplitude changes of cSII, cSII
      may play a role in pain perception.

PMID- 14715395
TI  - Marital functioning, chronic pain, and psychological distress.
AB  - This study examined whether marital functioning variables related uniquely to
      psychological distress and diagnoses of depressive disorder independent of pain
      severity and physical disability. Participants were 110 chronic musculoskeletal
      pain patients. Hierarchical regression results showed that marital variables
      (i.e. marital satisfaction, negative spouse responses to pain) contributed
      significantly to depressive and anxiety symptoms over and above the effects of
      pain severity and physical disability. In contrast, marital variables were not
      significantly related to diagnoses of depressive disorder (i.e. major depression,
      dysthymia, or both) after controlling for pain variables. In multivariate
      analyses, physical disability and marital satisfaction were uniquely related to
      depressive symptoms whereas physical disability, pain severity, and negative
      spouse responses to pain were uniquely related to anxiety symptoms. Only physical
      disability was uniquely related to major depression. The results suggest that
      models of psychological distress in chronic pain patients might be enhanced by
      attributing greater importance to interpersonal functioning and increasing
      attention to anxiety.

PMID- 14715396
TI  - Effects of 1-Hz repetitive transcranial magnetic stimulation on acute pain
      induced by capsaicin.
AB  - The aim of this study is to investigate the efficacy of 1-Hz repetitive
      transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on
      acute pain induced by intradermal capsaicin injection and to elucidate its
      mechanisms by single-photon emission computed tomography (SPECT). We compared
      time courses of a subjective scale of pain induced by intradermal capsaicin
      injection in seven normal subjects under three different conditions: rTMS over
      M1, sham stimulation, and control condition (natural course of acute pain without
      any stimulation). In ten normal subjects, using SPECT, we also studied
      differences in regional cerebral blood flow (rCBF) after capsaicin injection
      between two conditions: rTMS over M1 and the control condition. rTMS over M1
      induced earlier recovery from acute pain compared with the sham or control
      conditions. Under rTMS over the right M1 condition compared with the control
      condition, the SPECT study demonstrated a significant relative rCBF decrease in
      the right medial prefrontal cortex (MPFC) corresponding to Brodmann area (BA) 9,
      and a significant increase in the caudal part of the right anterior cingulate
      cortex (ACC) corresponding to BA24 and the left premotor area (BA6). A region-of
      interest analysis showed significant correlation between pain reduction and rCBF
      changes in both BA9 and BA24. We conclude that rTMS over M1 should have
      beneficial effects on acute pain, and its effects must be caused by functional
      changes of MPFC and caudal ACC.

PMID- 14715397
TI  - Oral health attitudes and communication with laypersons about orofacial pain
      among middle-aged and older adults.
AB  - Communication patterns with persons outside the health care system during a pain
      episode are poorly understood, yet can have a significant influence on patient
      behavior. This study examined associations between attitudes and beliefs about
      oral disease and dental care and talking about orofacial pain with laypersons and
      health care professionals. The subjects were 724 participants in the Florida
      Dental Care Study, a longitudinal study of oral health among community-dwelling
      adults. This study used a prospective design with data collected at baseline and
      the 42-month follow-up using a standardized interview format. Persons with
      negative attitudes and beliefs were more likely to have talked to a layperson
      about pain and less likely to have talked to a health care provider. In addition,
      the attitude that most consistently differentiated between respondents who had
      communicated only with a layperson from those who had talked to a health care
      provider was quality of recent visits, a variable representing more of the
      interpersonal aspects of a health care visit than the eventual outcomes from the
      treatment received. Our data are consistent with the hypothesis that lay
      consultation during a pain episode may substitute for formal care for persons
      with less positive views of the health care system. Intensity ratings and
      temporal characteristics of pain were also important determinants of these pain
      related communication patterns. These findings emphasize the importance of
      understanding the communication between persons with pain and non-health care
      professionals, and how these attitudes and communication preferences relate to
      the management of pain.

PMID- 14715398
TI  - Subcutaneous administration of botulinum toxin A reduces formalin-induced pain.
AB  - Botulinum toxin type A (BoNT-A) produced by the bacterium Clostridium botulinum
      is a potent inhibitor of acetylcholine release in the neuromuscular junction and
      has been used to treat many disorders related to excessive muscle contraction.
      However, BoNT-A has recently been used in pain therapy to treat myofascial pain,
      low back pain and various types of headaches, including migraine. The purpose of
      this study is to investigate the antinociceptive effect of BoNT-A and its
      underlying mechanism in the rat formalin inflammatory pain model. BoNT-A (3.5, 7,
      15 and 30 U/kg) or vehicle was administered to the plantar surface of the right
      hindpaw of male Sprague-Dawley rats. BoNT-A dose-dependently (P<0.05) inhibited
      formalin-induced nociceptive behavior during phase 2 but not during phase 1 when
      administered 5 h to 12 days before formalin challenge. The onset of the
      antinociceptive effect started at 5 h after pre-treatment and this effect lasted
      for at least 12 days. BoNT-A (7 U/kg) also reduced edema. Consistent with the
      lack of effect in the formalin phase 1, BoNT-A, at 15 U/kg, had no effect on
      acute thermal nociception; no local muscle weakness was observed at this dose.
      Pre-treatment of rats with BoNT-A (3.5, 7 or 15 U/kg) all significantly reduced
      formalin-evoked glutamate (Glu) release. These results demonstrate that local
      peripheral injection of BoNT-A significantly reduces formalin-induced nociceptive
      behaviors with the absence of obvious muscle weakness. Such an antinociceptive
      effect of BoNT-A is associated with the inhibition of formalin-induced release of
      Glu (and/or neuropeptides) from primary afferent terminals.

PMID- 14715399
TI  - Depression as a risk factor for onset of an episode of troublesome neck and low
      back pain.
AB  - The objective of this study is to determine whether depression is an independent
      risk factor for onset of an episode of troublesome neck and low back pain. There
      is growing evidence that pain problems increase the risk of depression. However,
      the evidence about the role of depression as a risk factor for onset of pain
      problems is contradictory. This lack of consistency in research findings may be
      due in part to methodological weaknesses in existing studies, for example, use of
      an inappropriate study design and inadequate consideration of confounding. A
      population-based random sample of adults was surveyed and followed at 6 and 12
      months. Individuals at risk of troublesome (intense and/or disabling) neck or low
      back pain are the subjects of this report (n=790). We used Cox proportional
      hazards models to measure the time-varying effect of depressive symptoms on the
      onset of troublesome neck and low back pain. Our multivariable analysis
      considered the possible confounding effects of demographic and socio-economic
      factors, health status, co-morbid medical conditions and injuries to the neck or
      low back. We found an independent and robust relationship between depressive
      symptoms and onset of an episode of pain. In comparison with the lowest quartile
      of scores (the least depressed), those in the highest quartile of depression
      scores had a four-fold increased risk of troublesome neck and low back pain
      (adjusted HRR 3.97; 95% CI 1.81-8.72). Depression is a strong and independent
      predictor for the onset of an episode of intense and/or disabling neck and low
      back pain.

PMID- 14715400
TI  - Phantom phenomena in mastectomized patients and their relation to chronic and
      acute pre-mastectomy pain.
AB  - Chronic and acute pre-mastectomy pain as well as prevalence and characteristics
      of phantom phenomena following mastectomy were investigated by interview in a
      sample of 39 women who had undergone unilateral breast amputation. Twenty of 39
      participants reported phantom sensations in the breast. Nine of the participants
      with phantom sensations experienced phantom pain and 11 non-painful phantom
      sensations. Although some features of phantom breast phenomena appear to be
      similar to characteristics of phantom phenomena in limb amputees, phantom breast
      phenomena seem to differ in a variety of ways such as time of onset or
      localization. This difference may be explained by the absence of kinesthesis and
      the small representation of the human breast. Seven of the 39 participants
      experienced chronic and six acute breast pain prior to the amputation. The amount
      of chronic pre-mastectomy breast pain weighted by the amount of involved tissue
      was significantly higher among participants with non-painful phantom sensations,
      compared to women with painful phantoms and those without phantom phenomena.

PMID- 14715401
TI  - Novel mechanism of enhanced nociception in a model of AIDS therapy-induced
      painful peripheral neuropathy in the rat.
AB  - To elucidate the underlying mechanisms involved in AIDS therapy-induced
      peripheral neuropathy, we have developed a model of nucleoside analog reverse
      transcriptase inhibitor-induced painful peripheral neuropathy in the rat, using
      2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI) and 2',3'-didehydro-3'
      deoxythymidine (d4T), AIDS chemotherapeutic drugs that are also components of
      AIDS highly active anti-retroviral therapy. Administration of ddC, ddI and d4T
      produced dose-dependent mechanical hypersensitivity and allodynia. Peripheral
      administration of inhibitors of protein kinase A, protein kinase C, protein
      kinase G, p42/p44-mitogen-activated protein kinase (ERK1/2) and nitric oxide
      synthase, which have demonstrated anti-hyperalgesic effects in other models of
      metabolic and toxic painful peripheral neuropathies, had no effect on ddC-, ddI-
      and d4T-induced hypersensitivity. Since suramin, an anti-parasitic and anti
      cancer drug, which shares with the anti-retroviral nucleoside analogs,
      mitochondrial toxicity, altered regulation of intracellular calcium, and a
      sensory neuropathy in humans, also produced mechanical hypersensitivity that was
      not sensitive to the above second messenger inhibitors we evaluated the role of
      intracellular calcium. Intradermal or spinal injection of intracellular calcium
      modulators (TMB-8 and Quin-2), which had no effect on nociception in control
      rats, significantly attenuated and together eliminated ddC and suramin-induced
      mechanical hypersensitivity. In electrophysiology experiments in ddC-treated
      rats, C-fibers demonstrated alterations in pattern of firing as indicated by
      changes in the distribution of interspike intervals to sustained suprathreshold
      stimuli without change in mechanical activation thresholds or in number of action
      potentials in response to threshold and suprathreshold stimulation. This study
      provides evidence for a novel, calcium-dependent, mechanism for neuropathic pain
      in a model of AIDS therapy-induced painful peripheral neuropathy.

PMID- 14715402
TI  - Acceptance of chronic pain: component analysis and a revised assessment method.
AB  - Acceptance of chronic pain entails that an individual reduce unsuccessful
      attempts to avoid or control pain and focus instead on participation in valued
      activities and the pursuit of personally relevant goals. Recent research suggests
      that pain-related acceptance leads to enhanced emotional and physical functioning
      in chronic pain patients above and beyond the influence of depression, pain
      intensity, and coping. In these studies, acceptance was measured using the
      Chronic Pain Acceptance Questionnaire (CPAQ). Preliminary analyses of the CPAQ
      have supported its psychometric properties. The present study sought to further
      refine the CPAQ by examining its factor structure and evaluating the relations of
      these factors to other indices of pain-related distress and disability. Although
      a previously demonstrated factor structure of the CPAQ was generally supported,
      only factors assessing (a) the degree to which one engaged in life activities
      regardless of the pain and (b) willingness to experience pain had adequate
      reliability and validity and were significantly related to the other measures of
      patient functioning. A revised version of the CPAQ is suggested.

PMID- 14715403
TI  - Verbally reinforcing pain reports: an experimental test of the operant model of
      chronic pain.
AB  - Effective treatments for chronic pain have been based on the operant model for
      chronic pain, which holds that pain behaviours can be operantly controlled by
      various reinforcers. Support for the operant model comes primarily from
      treatment/outcome studies which report significant reductions in pain behaviours
      in chronic pain patients, but fail to demonstrate the underlying operant thesis
      that various reinforcers play a significant role in the establishment and
      maintenance of pain behaviours. In an experimental test of this hypothesis, the
      pain reports of forty-six healthy undergraduate students were measured over two
      sets of fifteen trials, in which the pressure from a blood-pressure cuff applied
      to their arm either remained stable or decreased over time. Half of the subjects
      received positive verbal reinforcement from the experimenter after each trial if
      their report of pain intensity exceeded that of the previous trial. Overall, the
      mean pain reports of reinforced subjects were significantly greater than those of
      the non-reinforced subjects both when the intensity of the cuff was stable over
      trials, and when it decreased, as expected. These results provide support for the
      operant model of chronic pain. The clinical and theoretical implications of these
      results for the operant model of chronic pain are discussed, and suggestions for
      future research are made.

PMID- 14715404
TI  - Exercise and chronic low back pain: what works?
AB  - The aim of this review was to investigate current evidence for the type and
      quality of exercise being offered to chronic low back pain (CLBP) patients,
      within randomised controlled trials (RCTs), and to assess how treatment outcomes
      are being measured. A two-fold methodological approach was adopted: a
      methodological assessment identified RCTs of 'medium' or 'high' methodological
      quality. Exercise quality was subsequently assessed according to the predominant
      exercise used. Outcome measures were analysed based on current recommendations.
      Fifty-four relevant RCTs were identified, of which 51 were scored for
      methodological quality. Sixteen RCTs involving 1730 patients qualified for
      inclusion in this review based upon their methodological quality, and chronicity
      of symptoms; exercise had a positive effect in all 16 trials. Twelve out of 16
      programmes incorporated strengthening exercise, of which 10 maintained their
      positive results at follow-up. Supervision and adequate compliance were common
      aspects of trials. A wide variety of outcome measures were used. Outcome measures
      did not adequately represent the guidelines for impairment, activity and
      participation, and impairment measures were over-represented at the expense of
      others. Despite the variety offered, exercise has a positive effect on CLBP
      patients, and results are largely maintained at follow-up. Strengthening is a
      common component of exercise programmes, however, the role of exercise co
      interventions must not be overlooked. More high quality trials are needed to
      accurately assess the role of supervision and follow-up, together with the use of
      more appropriate outcome measures.

PMID- 14715405
TI  - Comment on: Tassain V, Attal N, Fletcher C, Brasseur L, Degieux P, Chauvin M,
      Bouhassira D. Long term effects of oral sustained release morphine on
      neuropsychological performance in patients with chronic non-malignant pain. Pain
      104: 389-400.

PMID- 14715407
TI  - Comment on Marquie L. et al. Pain rating by patients and physicians: evidence of
      systematic pain miscalibration (Pain 2003;102:289-96).

PMID- 14715409
TI  - Comment on 'Pulsed radiofrequency treatment of the gasserian ganglion in patients
      with idiopathic trigeminal neuralgia'.

PMID- 14715411
TI  - Chemokines: role in immune cell traffic.

PMID- 14715412
TI  - Unique pattern of expression and inhibition of IL-1 signaling by the IL-1
      receptor family member TIR8/SIGIRR.
AB  - TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the
      IL-1 receptor family. The present study was designed to investigate the
      expression and function of TIR8. TIR8 was mainly expressed in mouse and human
      epithelial tissues such as kidney, lung and gut. Resting and activated T and B
      lymphocytes and monocytes-macrophages expressed little or no TIR8, with the
      exception of the mouse GG2EE macrophage line. In the kidney, the organ with
      highest mRNA levels, TIR8 expression was confined to epithelial cells and, in
      situ, to tubular epithelium. A variety of signals failed to regulate TIR8
      expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter
      system was used to investigate the function of TIR8. TIR8 did not activate NF-kB
      expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling
      from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but
      the extracellular domain was dispensable for blocking activity. Thus, TIR8 is a
      unique member of the IL-1R family, with a distinct pattern of epithelial
      expression, including the kidney and mucosae, and an inhibitory function on IL-1
      signaling.

PMID- 14715413
TI  - Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the
      recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and
      MDC/CCL22.
AB  - Dendritic cells (DC) are potent antigen - presenting cells that can orientate the
      immune response towards a Th1 or a Th2 type. DC produce chemokines that are
      involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells
      such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES
      (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC)
      generated from healthy donors or from patients sensitive to Dermatophagoides
      pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of
      Dpt), could upregulate the expression of chemokines involved in type 1 or type 2
      T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the
      control and the chemokines produced were evaluated using ELISA and chemotaxis
      assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17)
      and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1
      pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion.
      RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC
      were from healthy or allergic donors. The selective Th2 clone recruitment
      activity of supernatants from Der p 1-pulsed DC of allergic patients was
      inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using
      anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy
      donors were shown to be involved in the recruitment of Th1 cells. These results
      suggest that in allergic patients exposed to house dust mites, DC may favour the
      exacerbation of the Th2 response via the increase in type 2 chemokine production.

PMID- 14715414
TI  - Perfusion of human term placentas with lipopolysaccharide did not affect the
      capacity of the fetal and maternal tissues to produce interleukin-10.
AB  - IL-10 is anti-inflammatory cytokine that is involved in the regulation of the
      pregnancy process. We examined the capacity of fetal and maternal placental
      tissues from human term placentas, to produce IL-10, in the presence and absence
      of LPS. The levels of IL-10 were examined (by ELISA and immunohistochemical
      staining) in the fetal and maternal tissues of human placentas after 10 hours of
      perfusion, in the presence or absence of lipopolysaccharide (LPS; 1 microg/k"g
      perfused tissue). We could detect IL-10 in amnion (A; 13.91+/-11.35 pg/ml) and
      chorion (CH; 7.85 +/- 6.38 pg/ml) tissue homogenates, and in the homogenates of
      three different sites of the placental tissue compartment (subchorionic placenta
      (SubCH); 7.39 +/- 4.39 pg/ml, mid-placenta (MidPL); 8.9 +/- 4.73 pg/ml and
      decidua (Decid); 16.48 + 11.86 pg/ml). Immunohistochemical studies showed that IL
      10 was localized in the epithelial cells of the amnion, and in the fibroblasts
      and macrophages of the chorion. In the placenta and mid-placental sites, IL-10 is
      localized mainly in cytotrophoblasts and syncytotrophoblasts. The presence of LPS
      in the perfusion media of the placentas for 10 hours, did not significantly
      affect the capacity of the fetal and maternal tissues to produce IL-10. Thus, our
      results may indicate the involvement of the fetal compartment in the down
      regulation of the cell-mediated response of the maternal compartment against the
      fetus, by producing IL-10 under physiological conditions. Infection/inflammation
      agents such as LPS did not affect the expression levels of IL-10 in the placenta.

PMID- 14715415
TI  - The cytokine synthesis by heterozygous carriers of the Toll-like receptor 4
      Asp299Gly polymorphism does not differ from that of wild type homozygotes.
AB  - Previous studies have found that heterozygosity for the A896G mutation of the
      endotoxin receptor TLR4 confers susceptibility to Gram-negative infections and
      septic shock. To evaluate the underlying mechanisms, we studied the association
      of the TLR4 polymorphism with endotoxin-induced cytokine synthesis in human whole
      blood. Monocyte CD14 density and monocyte count were also determined. Healthy
      individuals were genotyped by means of a real-time polymerase chain reaction.
      Plasma concentrations of TNF-alpha, IL-6, and IL-8 were measured by
      chemiluminescence. No significant differences in cytokine synthesis were observed
      between heterozygous individuals and homozygous carriers of the wild type allele.
      Our study suggests that heterozygosity for this TLR4 mutation is not a major
      factor determining the cytokine response to endotoxin.

PMID- 14715416
TI  - Severe malarial anemia associated with increased soluble Fas ligand (sFasL)
      concentrations in Gabonese children.
AB  - To investigate if severe malarial anemia is associated with specific cytokine
      overproduction, we evaluated serum levels of soluble Fas ligand (sFasL), tumor
      necrosis factor (TNF-alpha) and interleukin-10 (IL-10) from three groups of young
      children with Plasmodium falciparum infection (asymptomatic cases, uncomplicated
      malaria cases and severe malarial anemia cases), in a hyperendemic area of Gabon.
      In uncomplicated cases, only TNF levels were significantly (p < 0.001) increased
      in comparison to asymptomatic cases with P. falciparum infection. High levels of
      sFasL, TNF-alpha and IL-10 were associated with low hemoglobin concentrations,
      sFasL levels were significantly higher in children with severe malarial anemia (p
      < 0.001) as compared to both other groups. The parasite density was positively
      correlated with IL-10, TNF-alpha and sFasL levels. TNF-alpha and sFasL, but not
      IL-10 or parasitemia, were independent predictors of hemoglobin concentrations.
      These results suggest that, in malaria, a specific dysregulation of the cytokine
      balance may lead to complications such as severe anemia.

PMID- 14715417
TI  - Interleukin-1 receptor antagonist transiently impairs antibacterial defense but
      not survival in murine pneumococcal pneumonia.
AB  - The inhibition of the biological activity of IL-1 by recombinant human IL-1
      receptor antagonist (IL-1ra) has been investigated in several, controlled
      clinical trials. Encouraging results have been reported, in particular in
      patients with rheumatoid arthritis. In the present study, we investigated the
      influence of treatment of wild type mice with IL-1ra, which resulted in an
      incomplete and transient inhibition of IL-1 activity. Treatment with recombinant
      human IL-1ra resulted in an enhanced bacterial outgrowth in the lungs of BALB/c
      and C57BL/6 mice early after induction of pneumococcal pneumonia, without
      influencing survival or the pulmonary inflammatory response. The effect of IL-1ra
      on the host response to S. pneumoniae pneumonia is modest and transient. The
      present data, together with the findings in IL-1R*/* mice in earlier work,
      suggest that IL-1 occupies a role in the pulmonary immune response to S.
      pneumoniae that is substantially less prominent than that of TNF-alpha.

PMID- 14715418
TI  - Constitutive expression of TGF-beta1, interleukin-6 and interleukin-8 by tumor
      cells as a major component of immune escape in human ovarian carcinoma.
AB  - Tumors could use several mechanisms to coexist with the host's immune system or
      to protect themselves from an immune response. Thus, insufficient expression of
      cell surface molecules on tumor cells, which are important for T cell recognition
      or activation, could lead to induction of a state of tolerance. Tumor cells could
      also produce cytokines that would inhibit the immune response and allow tumor
      progression. Here, we studied, in vitro, the cell surface expression of
      immunologically important molecules in seven ovarian carcinoma (OVCA) cell lines
      and the constitutive expression of cytokines. All OVCA cell lines expressed MHC
      class I molecules, ICAM-1 and LFA-3 adhesion molecules, necessary to induce a
      specific cytotoxic T-cell response, as well as the CD40 costimulatory molecules.
      Conversely, the lack of the dominant costimulatory molecules, CD80 (B7.1) and
      CD86 (B7.2) could be a possible explanation of poor immunogenicity of OVCA
      tumors. Immunosuppressive TGF-beta1 was detected at the mRNA level in all cell
      lines but was weakly secreted in supernatants. By contrast, IL-10 was never
      found. Most of them constitutively produced IL-8 and IL-6, two cytokines known as
      tumor promoting factors whereas the proinflammatory cytokines TNF-alpha, IL-1beta
      and GM-CSF were rarely produced. Data from this study could be useful for
      designing new strategies of immunotherapy to improve immunogenicity and/or limit
      protumor cytokine production.

PMID- 14715419
TI  - Sepsis induces DNA fragmentation in rat skeletal muscle.
AB  - Recent studies have demonstrated the activation of skeletal muscle DNA
      fragmentation in some catabolic conditions. In an attempt to elucidate if sepsis
      (a catabolic state) was also associated with muscle apoptosis, sepsis was induced
      by cecal ligation and puncture, and the results clearly show an induction of DNA
      fragmentation in gastrocnemius muscle following the induction of the septic
      state. Administration of rolipram (an inhibitor of tumour necrosis factor-a (TNF
      alpha) synthesis) to septic rats clearly prevented the increased DNA
      fragmentation, suggesting that TNF-alpha is involved in the activation of the
      apoptotic events in septic rat skeletal muscle.

PMID- 14715420
TI  - [Erythropoietin and anemia: when quality of life and survival clash].

PMID- 14715421
TI  - [Topoisomerase I in alternative splicing].

PMID- 14715422
TI  - [Breast cancer screening after age 70].
AB  - Today, mammographic screening for breast cancer is recommended in France in the
      female population age 50 to 74. This recommendation is based on the analysis of
      all randomised studies. However, the available data show the risk of cancer to
      increase markedly with age. One excludes therefore from the screening programme,
      the women who are most likely to present with breast cancer. Should not one
      consider screening among older women?

PMID- 14715423
TI  - [Conditionally replicative adenoviruses: a second wind for cancer gene therapy].
AB  - Cancer gene therapy has offered many hopes but its first use in humans revealed
      some pitfalls and at least three main problems: lack of efficacy and specificity
      of current vectors to deliver therapeutic genes, poor diffusion of the
      therapeutic effects inside the tumor (absence of bystander effect), poor
      distribution of the vectors injected inside the tissue. To address some of these
      issues, several teams have developed tumor selective replicating adenoviruses,
      some of them being already in the clinic. First results are promising but
      complementary studies are needed to define if these agents will take place in the
      therapeutic armentorium against cancer.

PMID- 14715424
TI  - [Sentinel node identification in breast cancer: logistic aspects].
AB  - Sentinel node identification has gained its place in early breast cancer surgical
      management before the results of prospective randomized trials. Published results
      can be explained by teams configurations and technical aspects can create some
      confusion in results analysis. Logistic aspects confers a specificity for each
      team. Sentinel node technique should be reserved to experienced treatment center
      where it can be utilized routinely.

PMID- 14715425
TI  - [Molecular therapy targets in lung cancer].
AB  - Molecular targeted therapies offer great hope in lung cancer because they are
      supposed to act upon biologic abnormalities specific to cancer cells. In the
      present review, we will describe the major pathways of tumor cell growth,
      apoptosis, angiogenesis and invasion as well as the targeted therapies
      interacting with these pathways. We will provide an overview of the trials
      involving targeted therapies in lung cancer, along with the specific problems
      related to the development of these new therapies.

PMID- 14715426
TI  - [Intra-abdominal desmoplastic small round cell tumor in childhood: case report
      and review of the literature].
AB  - Desmoplastic small round cell tumor (DSRCT) correspond to a recent
      clinicopathological entity, individualized in 1989 into the group of tumors with
      small round cells. This pathology puts ethiopathogenic, diagnostic, therapeutic
      and prognosis problems. Indeed, the ethiopathogenic is still unknown, diagnosis
      is asserted only by immuno-histochimic and cytogenetic study because of the big
      number of differential diagnoses and the anatomopathologic polymorphism. Its
      treatment is not well codified and its outcome remains dark in spite of
      therapeutic progress. The objective of this work is to report a personal
      observation of a DSRCT and to proceed to a review of the literature to clarify
      the epidemiological, clinical, paraclinical and therapeutic aspects of this rare
      tumor.

PMID- 14715427
TI  - [Focus on cellular pharmacology of docetaxel].
AB  - Docetaxel, a member of the taxoid class of antineoplasic agents, is derived from
      an inactive precursor obtained from the needles of the European yew. Docetaxel is
      characterised by a wide spectrum of in vitro cytotoxicity an murine and human
      tumour cell lines and in vivo antitumour activity against human tumour
      xenografted in athymic mice. The principal mechanism by which docetaxel exerts
      its cytotoxic activity is through enhancement and stabilisation of microtubule
      assembly leading to an arrest of the cell cycle at the G2/M phase. It has also
      been shown to induce tumour cell death by apoptosis and to have antiangiogenic
      and immunostimulating properties. Docetaxel demonstrated in vitro and/or in vivo
      additive and synergistic effects when combined with a large spectrum of
      anticancer therapies such as new cytotoxic agents (gemcitabine, capecitabine,
      edatrexate), specific signal transduction drugs, Herceptin, antiangiogenic drugs,
      gene therapy, or antisense olignonucleotides, opening to new treatment
      strategies. Despite close chemical structures, preclinical data suggested a
      difference in the cellular pharmacology of docetaxel and paclitaxel leading to
      different profiles in clinical studies.

PMID- 14715428
TI  - [Clinical practice guidelines: Standards, Options and Recommendations for the
      diagnosis of carcinomas of unknown primary site].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which
      started in 1993, is a collaboration between the Federation of French Cancer
      Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from
      French public universities, general hospitals and private clinics. The main
      objective is the development of clinical practice guidelines to improve the
      quality of health care and the outcome of cancer patients. OBJECTIVES: To define
      Clinical Practice Guidelines (CPG) for the diagnosis of carcinomas of unknown
      primary site. METHODS: The methodology is based on a literature review and
      critical appraisal by a multidisciplinary group of experts who define the CPGs
      according to the definitions of the Standards, Options and Recommendations
      project. Once the guidelines has been defined, the document is submitted for
      review by independent reviewers. RESULTS: The main recommendations for the
      diagnosis of carcinomas of unknown primary site are: 1) Diagnostic strategy
      should aim to identify anatomoclinical entities of carcinomas of unknown primary
      site for which there is a specific treatment. For other anatomoclinical entities,
      identification of the primary tumour has no impact on the prognostic or
      therapeutic consequences, thus a systematic complete assessment is unnecessary.
      2) An immunohistochemical investigation for the diagnosis should be performed
      using an appropriate panel of specific antibodies. This should enable the
      diagnosis of lymphoma, melanoma, germ cell tumour and sarcoma to be eliminated
      and the diagnosis of prostate, breast, ovary, thyroid or neuroendocrine tumours
      to be positively identified. 3) A sample can be frozen to enable typing,
      cytogenetic and, particularly, molecular biological studies to be performed
      later. 4) The clinician and pathologist should compare their opinions before and
      after the pathological diagnosis.

PMID- 14715429
TI  - [Bisphosphonates, pain and quality of life in metastatic breast cancer patients:
      a literature review].
AB  - Bisphosphonates constitute the standard treatment for cancer hypercalcemia and
      prevention of complications of metastatic bone disease. Various clinical
      endpoints have been used to evaluate the impact of bisphosphonates on bone
      metastases. This literature review is focused on the analgesic effect of
      bisphosphonates and their impact on quality of life (QoL) in patients with bone
      metastases from breast cancer. Twenty-five randomized trials studying
      bisphosphonates with pain and/or QoL as primary or secondary endpoints were
      considered. These studies were analyzed with following criterias : study type,
      primary cancer, drug scheduling, number of patients included, associated specific
      treatment, primary and secondary endpoints, pain assessment, and QoL assessment.
      The results are in favor of an efficacy of bisphosphonates in bone pain, even
      when not always statistically significant and with an important variability in
      assessment criterias and tools. QoL assessment with validated, reliable scales
      (EORTC QLQ-C30, Rotterdam Symptom Checklist...) has been performed in 9 studies.
      The use of bisphosphonates with systemic and radiation therapy increases QoL or
      reduces QoL deterioration. Despite some methodological limitations, these studies
      indicate a beneficial effect on bone pain, and an improvement in the QoL of
      patients with metastatic bone disease of breast cancer. Because of a lack of
      systemic data, reliable analysis of the results is difficult. Several questions
      remain open about which bisphosphonates and route of administration to choose,
      and the variable effects on different primaries.

PMID- 14715430
TI  - [External beam radiation therapy and interstitial brachytherapy in the treatment
      of anal canal carcinomas: a series of 70 patients].
AB  - This study is concerning 70 patients (57 female, 13 male) with an epidermoid
      carcinoma of the anal canal which were treated homogeneously with a combination
      of an external beam radiation therapy ((45 Gy in 25 fractions of 1.8 Gy for 5
      weeks) and a brachytherapy with Iridium wires (15 to 20 Gy delivered to the gross
      residual disease). The N1 patients and the patients with tumors more than 4 cm in
      diameter received a chemotherapy also (5 FU and cisplatinum). The overall local
      control was obtained in 68 cases out of 70 (97.1%). 63 out of 70 patients (90%)
      are alive and locally controlled. 56 pts out of 70 (80%) did have a preserved
      anus, and a normal sphincterian function was preserved in 53 pts out of 70
      (75.7%). 17 pts had a colostomy (3 without and 14 with an abdominoperineal
      resection). With the salvage perineal resection, 11 patients out of 12 local
      recurrences were definitely locally cured (91.7%). The 5-year overall survival is
      91.4%. The 5-year disease-free survival is 90%. The 5-year survival with
      preserved anal sphincter is 80% and with preserved sphincterian function is
      75.7%. Five patients died from cancer (3 deaths due to metastases, and only 2 due
      to a locoregional evolution). These results have been analysed regarding the
      literature data and demonstrated the curative role of external beam and
      brachytherapy, in localized tumors, the contribution of chemotherapy in advanced
      stages and the efficiency of secondary salvage surgery in local recurrences.

PMID- 14715431
TI  - Reduced COMT activity as a possible environmental risk factor for breast cancer.
      Opinion.
AB  - Recent genetic epidemiological studies implicate a low activity form of catechol
      O-methyltransferase (COMT) with increased risk factor for breast cancer. Taking
      into account, the role of COMT in the metabolism of otherwise carcinogenic
      catecholestrogens, it is reasonable to propose that environmental or dietary
      products that inhibit COMT pose a risk for breast cancer.

PMID- 14715432
TI  - Neuropathological and biochemical features of traumatic injury in the developing
      brain.
AB  - Trauma to the developing brain constitutes a poorly explored field. Some recent
      studies attempting to model and study pediatric head trauma, the leading cause of
      death and disability in the pediatric population, revealed interesting aspects
      and potential targets for future research. Trauma triggers both excitotoxic and
      apoptotic neurodegeneration in the developing rat brain. Excitotoxic
      neurodegeneration develops and subsides rapidly (within hours) whereas apoptotic
      cell death occurs in a delayed fashion over several days following the initial
      traumatic insult. Apoptotic neurodegeneration contributes in an age-dependent
      fashion to neuronal injury following head trauma, with the immature brain being
      exceedingly sensitive. In the most vulnerable ages the apoptosis contribution to
      the extent of traumatic brain damage far outweighs that of the excitotoxic
      component. Molecular and biochemical studies indicate that both extrinsic and
      intrinsic mechanisms are involved in pathogenesis of apoptotic cell death
      following trauma. Interestingly, in infant rats a pan-caspase inhibitor
      ameliorated apoptotic neurodegeneration with a therapeutic time window of up to 8
      h after trauma. These results help explain unfavorable outcomes of very young
      pediatric head trauma patients and imply that regimens which target slow active
      forms of cell death may comprise a successful neuroprotective approach.

PMID- 14715433
TI  - Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure
      in the pathogenesis of Azheimer disease.
AB  - Chronic vascular hypoperfusion induces oxidative stress and brain energy failure,
      and leads to neuronal death, which manifests as cognitive impairment and the
      development of brain pathology as in Alzheimer disease (AD). It is becoming more
      widely accepted that AD is characterized by impairments in energy metabolism. We
      hypothesize that hypoperfusion-induced mitochondrial failure plays a central role
      in the generation of reactive oxygen species, resulting in oxidative damage to
      brain cellular compartments, especially in the vascular endothelium and neuronal
      cell bodies in AD. All of these changes have been found to occur before pathology
      and coexist during the progression of AD. In this review we have summarized
      recent evidence and our own knowledge regarding the relationship between the
      hypoperfusion-induced vascular damage that initiates oxidative stress and
      mitochondrial abnormalities that appear to be a key target for the development of
      AD pathology. Future investigations into both the mechanisms behind amyloid beta
      (Abeta) deposition and the possible accelerating effects of environmental
      factors, such as chronic hypoxia/reperfusion may open the door for effective
      pharmacological treatments of AD. We hypothesize that an imbalance between
      endothelium derived vasoconstrictors and vasodilators, along with an antioxidant
      system deficiency and mitochondria lesions are prominent in AD. Future studies
      examining the importance of mitochondrial pathophysiology in different brain
      cellular compartments may provide insight not only into neurodegenerative and/or
      cerebrovascular disease pathobiology but may also provide targets for treating
      these conditions.

PMID- 14715434
TI  - Effect of the proteasome inhibitor MLN519 on the expression of inflammatory
      molecules following middle cerebral artery occlusion and reperfusion in the rat.
AB  - Anti-inflammatory treatment with the proteasome inhibitor MLN519 has been
      previously reported to be neuroprotective against ischemic brain injury in rats.
      These effects have been related to inhibition of the transcription factor NF
      kappaB, which is activated through ubiquitin-proteasomal degradation. The aim of
      this study was to evaluate the effects of MLN519 to alter the expression of
      several inflammatory genes under the control of NF-kappaB. Male Sprague-Dawley
      rats underwent middle cerebral artery occlusion (MCAo) followed by vehicle or
      MLN519 (1.0 g/kg, i.v.) treatment immediately after reperfusion of blood to the
      brain at 2h. Gene expression was evaluated 3-72 h post-MCAo. The most striking
      effects of intravenous treatment with MLN519 were associated with reductions in
      ICAM-1 expression at 3 h followed by reductions in E-selectin (12-72 h). Less
      dramatic reductions were observed in IL-1Beta (3-24 h) and TNF-Alpha (24 h) with
      no apparent effects on IL-6 and VCAM-1 mRNA levels. Immunohistochemical analysis
      revealed that the genes most dramatically affected by MLN519 had highest
      expression in endothelial cells and leukocytes (E-selectin, ICAM-1),indicating
      that these cell types may be the primary targets of intravenously delivered
      MLN519 treatment.

PMID- 14715435
TI  - Acrolein inhibits NADH-linked mitochondrial enzyme activity: implications for
      Alzheimer's disease.
AB  - In Alzheimer's disease (AD) brain increased lipid peroxidation and decreased
      energy utilization are found. Mitochondria membranes contain a significant amount
      of arachidonic and linoleic acids, precursors of lipid peroxidation products, 4
      hydroxynonenal (HNE) and 2-propen-1-al (acrolein), that are extremely reactive.
      Both alkenals are increased in AD brain. In this study, we examined the effects
      of nanomolar levels of acrolein on the activities of pyruvate dehydrogenase (PDH)
      and Alpha-ketoglutarate dehydrogenase (KGDH), both reduced nicotinamide adenine
      dinucleotide (NADH)-linked mitochondrial enzymes. Acrolein decreased PDH and KGDH
      activities significantly in a dose-dependent manner. Using high performance
      liquid chromatography coupled to mass spectrometry (HPLC-MS), acrolein was found
      to bind lipoic acid, a component in both the PDH and KGDH complexes, most likely
      explaining the loss of enzyme activity. Acrolein also interacted with oxidized
      nicotinamide adenine dinucleotide (NAD(+)) in such a way as to decrease the
      production of NADH. Acrolein, which is increased in AD brain, may be partially
      responsible for the dysfunction of mitochondria and loss of energy found in AD
      brain by inhibition of PDH and KGDH activities, potentially contributing to the
      neurodegeneration in this disorder.

PMID- 14715436
TI  - Regulation of tyrosine hydroxylase expression in tottering mouse Purkinje cells.
AB  - Tottering (tg) mice inherit a missense mutation in the Alpha1A subunit of P/Q
      type calcium channels. This mutation results in an increased density of L-type
      calcium channels in the cerebellum and abnormal regulation of tyrosine
      hydroxylase (TH) gene expression in a subset of cerebellar Purkinje cells, a cell
      type that does not normally express TH. The behavioral phenotype includes attacks
      of dyskinesia, which can be blocked by L-type calcium channel antagonists. To
      test the hypothesis that cerebellar TH mRNA expression can be manipulated in vivo
      by L-type calcium channel blockade, control and tottering mice were chronically
      treated with the L-type calcium channel antagonist nimodipine. Chronic nimodipine
      treatment significantly reduced the expression of TH mRNA in tottering mouse
      Purkinje cells. This effect was observed without altering the increased density
      of L-type calcium channels in tottering mouse cerebella. Chronic nimodipine
      treatment had no effect on TH mRNA expression in tottering mouse
      catecholaminergic neurons, including those of the locus coeruleus and substantia
      nigra. However, a small reduction in TH mRNA expression in the substantia nigra
      of control mice was observed after drug treatment. These data suggest that the
      abnormal expression of TH in tottering mouse Purkinje cells is regulated by
      Purkinje cell excitability.

PMID- 14715437
TI  - Mitochondrial complex I inhibition produces selective damage to hippocampal
      subfield CA1 in organotypic slice cultures.
AB  - The effects of mitochondrial respiratory chain inhibitors and the excitotoxin N
      methyl-D-aspartate (NMDA) on cell death in hippocampal subfields CA1 and CA3 were
      examined in hippocampal organotypic slice cultures. Slice cultures, 2-3 week old,
      were exposed for 1 h to either the Complex I inhibitors, rotenone or 1-methyl-4
      phenylpyridium (MPP+), the Complex II inhibitor 3-nitropropionic acid (3-NP), or
      the excitotoxin NMDA. Cell death was examined 24 and 48 h following treatment, by
      measuring propidium iodide (PI) fluorescence. Treatment with 1 micro M Rotenone
      caused greater cell death in hippocampal subfield CA1 than CA3. Exposure of
      hippocampal slice cultures to 10 micro M rotenone, to MPP+ or to NMDA resulted in
      damage to both CA1 and CA3 subfields. 3-NP produced little damage in either
      subfield. The data suggest that mitochondrial Complex I inhibition can produce
      selective cell damage in hippocampus and in this regard is similar to that
      observed following hypoxia/ischemia.

PMID- 14715438
TI  - Protective effects of adenoviral cardiotrophin-1 gene transfer on rubrospinal
      neurons after spinal cord injury in adult rats.
AB  - Cardiotrophin-1 (CT-1), a muscle-derived cytokine, supports the survival of
      motoneurons in vivo and in vitro. The present study investigated whether
      adenoviral huCT-1 gene transfer protected injured neurons from cell death or
      atrophy and promoted regeneration of rubrospinal tract (RST) after spinal cord
      injury in adult rats. Administration of the adenoviral CT-1 vector (Adv-CT1) to
      C3-4 lateral funiculus hemisection cavity, that completely interrupted RST, led
      to sustained CT-1 expression. Providing Adv-CT1, which rescued 20% of neurons,
      could prevent the loss of injured rubrospinal neurons 8 weeks post-injury.
      Retrograde tracing with FluoroGold showed that 1.2% of RST neurons regenerated at
      least two segments caudal to the injury site. Anterograde tracing with
      biotinylated dextran amine revealed that the RST axons terminated in white matter
      and gray matter. Behavioral testing revealed a significant functional recovery in
      limb usage. This observation indicated that adenoviral CT-1 gene transfer into
      the injured cord promoted survival and regeneration of rubrospinal neurons in
      adult rats.

PMID- 14715439
TI  - Hyperactivity following postnatal NMDA antagonist treatment: reversal by D
      amphetamine.
AB  - Three experiments were performed to study the effects of neonatal administration
      of glutamate receptor antagonists, on either Day 11 (dizocilpine = MK-801, 3 x
      0.5 mg/kg, s.c., injected at 0800, 1600 and 2400 h) or Day 10 (Ketamine, 1 x 50
      mg/kg, s.c., or Ethanol-Low, 1 x 2.5 mg/kg, or, Ethanol-High, 2 x 2.5 mg/kg,
      s.c., with 2-h interval) to male mice pups, on spontaneous motor behavior,
      habituation to a novel situation and D-amphetamine-induced activity in the adult
      animals. Mice administered MK-801 showed initial hypoactivity followed by
      hyperactivity over the later (20-40 and 40-60 min) periods of testing. Mice
      administered Ketamine and Ethanol-High similarly displayed an initial
      hypoactivity followed by hyperactivity over the later time (20-60 min) of
      testing. Habituation to the novel activity test chambers was reduced drastically
      in the MK-801 mice compared with vehicle-treated mice. Similarly, mice
      administered Ketamine and Ethanol-High displayed too drastically reduced
      habituation behavior. The low dose of D-amphetamine (0.25 mg/kg) reduced the
      hyperactivity of neonatal MK-801-treated mice, particularly from 30-60 min
      onwards, and elevated the activity level of the vehicle-treated mice. Similarly,
      the low dose of D-amphetamine (0.25 mg/kg) reduced the hyperactivity of
      neonatally Ketamine-treated and Ethanol-High-treated mice, particularly from 30
      60 min onwards, and elevated the activity level of the respective vehicle-treated
      mice. Fluoro-jade staining per mm(2) regional brain tissue of MK-801 mice pups
      expressed as percent of vehicle mice pups showed also that the extensiveness of
      staining was markedly greater in the parietal cortex, hippocampus, frontal
      cortex, and lesser so in the laterodorsal thalamus. Ketamine-treated mice showed
      cell degeneration mainly in the parietal cortex, whereas the Ethanol-High mice
      showed marked cell degeneration in both the parietal and laterodorsal cortex. The
      present findings that encompass a pattern of regional neuronal degeneration,
      disruptions of spontaneous motor activity, habituation deficits and reversal of
      hyperactivity by a low dose of D-amphetamine suggest a model of Attention Deficit
      Hyperactivity Disorder that underlines the intimate role of N-methyl-D-aspartate
      (NMDA) receptors in the developing brain.

PMID- 14715440
TI  - Novel mechanisms and approaches in the study of neurodegeneration and
      neuroprotection. a review.
AB  - Cellular mechanisms involved in neurodegeneration and neuroprotection are
      continuing to be explored, and this paper focuses on some novel discoveries that
      give further insight into these processes. Oligodendrocytes and activated
      astroglia are likely generators of the pro-inflammatory cytokines, such as the
      tumor necrosis factor family and interleukin family, and these glial support
      cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion
      molecules (ICAM) that have a major role in neuronal apoptosis. Even brief
      exposure to some substances, in ontogeny and sometimes in adulthood, can have
      lasting effects on behaviors because of their prominent toxicity (e.g., NMDA
      receptor antagonists) or because they sensitize receptors (e.g., dopamine D2
      agonists), possibly permanently, and thereby alter behavior for the lifespan.
      Cell cycle genes which may be derived from microglia, are the most-recent entry
      into the neuroprotection schema. Neuroprotection afforded by some common
      substances (e.g., melatonin) and uncommon substances [e.g., nicotine, green tea
      polyphenol (-)-epigallocatechin-3-gallate (EGCG), trolox], ordinarily thought to
      be simple radical scavengers, now are thought to invoke previously unsuspected
      cellular mechanisms in the process of neuroprotection. Although Alzheimer's
      disease (AD) has features of a continuous spectrum of neural and functional
      decline, in vivo PET imaging and and functional magnetic resonance imaging,
      indicate that AD can be staged into an early phase treatable by inhibitors of
      beta and gamma secretase; and a late phase which may be more amenable to
      treatment by drugs that prevent or reverse tau phosphorylation. Neural
      transplantation, thought to be the last hope for neurally injured patients (e.g.,
      Parkinsonians), may be displaced by non-neural tissue transplants (e.g., human
      umbilical cord blood; Sertoli cells) which seem to provide similar neurotrophic
      support and improved behavior - without posing the major ethical dilemma of
      removing tissue from aborted fetuses. The objective of this paper is to invite
      added research into the newly discovered (or postulated) novel mechanisms; and to
      stimulate discovery of additional mechanisms attending neurodegeneration and
      neuroprotection.

PMID- 14715441
TI  - Coupled reductions in brain oxidative phosphorylation and synaptic function can
      be quantified and staged in the course of Alzheimer disease.
AB  - In vivo, post-mortem and biopsy data suggest that coupled declines occur in brain
      synaptic activity and brain energy consumption during the evolution of Alzheimer
      disease. In the first stage of these declines, changes in synaptic structure and
      function reduce neuronal energy demand and lead to potentially reversible
      downregulation of oxidative phosphorylation (OXPHOS) within neuronal
      mitochondria. At this stage, measuring brain glucose metabolism or brain blood
      flow in patients, using positron emission tomography (PET), shows that the brain
      can be almost normally activated in response to stimulation. Thus, therapy at
      this stage should be designed to re-establish synaptic integrity or prevent its
      further deterioration. As disease progresses, neurofibrillary tangles with
      abnormally phosphorylated tau protein accumulate within neuronal cytoplasm, to
      the point that they co-opt the nonphosphorylated tau necessary for axonal
      transport of mitochondria between the cell nucleus and the synapse. In this
      second stage, severe energy depletion and other pathological processes associated
      with irreversibly downregulated OXPHOS lead to cell death, and the brain cannot
      normally respond to functional stimulation.

PMID- 14715442
TI  - Involvement of nitric oxide on kainate-induced toxicity in oligodendrocyte
      precursors.
AB  - The vulnerability of oligodendrocytes to excitatory amino acids may account for
      the pathology of white matter occurring following hypoxia/ischemia or autoimmune
      attack. Here, we examined the vulnerability of immature oligodendrocytes
      (positively labeled by galactocerobroside-C and not expressing myelin basic
      protein) from neonatal rat spinal cord to kainate, an agonist of excitatory amino
      acid receptors that induces long-lasting inward currents in immature
      oligodendrocytes. In particular, we studied whether kainate toxicity was linked
      to the endogenous production of nitric oxide. We found cultured oligodendrocytes
      to be highly sensitive to 24-48 h exposure to 0.5-1 mM kainate. The toxin induced
      striking morphological changes in oligodendrocytes, characterized by the
      disruption of the process network around the cell body and the growth of one or
      two long, thick and non-branched processes. A longer exposure to kainate resulted
      in massive death of oligodendrocytes, which was prevented by 6,7,
      dinitroquinoxaline-2,3-dione (DNQX) (30 micro M), the antagonist of AMPA (alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic/kainate receptors. Remarkably, we
      found that those oligodendrocytes displaying bipolar morphology following kainate
      exposure, also expressed the inducible form of nitric oxide synthase (iNOS) and
      nitrotyrosine immunoreactivity, suggesting that peroxynitrite could be formed by
      the reaction of nitric oxide with superoxide. Moreover, kainate toxicity was
      significantly prevented by addition of the NOS inhibitor nitro-L-arginine methyl
      ester (L-NAME), further suggesting that nitric oxide-derived oxidants contribute
      to excitotoxic mechanisms in immature oligodendrocytes.

PMID- 14715443
TI  - MPP(+)-induced degeneration is potentiated by dicoumarol in cultures of the RCSN
      3 dopaminergic cell line. Implications of neuromelanin in oxidative metabolism of
      dopamine neurotoxicity.
AB  - We have tested the idea that oxidative metabolism of dopamine may be involved in
      MPTP toxicity using the RCSN-3 cell line derived from the substantia nigra of an
      adult rat. Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (10
      microM), MPTP combined with 40 microM dicoumarol (an inhibitor of DT-diaphorase)
      and dicoumarol alone, did not induce toxicity in RCSN-3 cells after 72 h
      incubation. The lack of toxicity in MPTP-treated RCSN-3 cells may be explained by
      the fact that they are unable to metabolize MPTP to 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridinium ion (MPP+ as determined by HPLC. Incubation for 72 h with
      100 microM MPP+ induced a 6.6 +/- 1.4% cell death of RCSN-3 cells compared to 3.5
      +/- 0.4 observed in control cells. However, when the cells were treated with 100
      microM MPP+ and 40 microM dicoumarol, cell death increased 4-fold compared to
      that of cells treated solely with MPP+ (27 +/- 2%; P<0.001). Under these
      conditions, a significant increase in DNA fragmentation (3-fold compared to MPP+
      alone; P<0.01) and in calpain activation (P<0.05 compared to control) was
      evident. The inhibition of DT-diaphorase by dicoumarol supports the idea that
      oxidative metabolism of dopamine is involved in MPP+ toxicity in RCSN-3 cells.

PMID- 14715444
TI  - Parkinson's disease and inflammatory changes.
AB  - In 1988 McGeer and colleagues (Neurology 38, 1285-91) observed an activation of
      the microglia in substantia nigra pars compacta (SNpc) and striatum of brains
      from patients with Parkinson's disease. In the years that followed several
      studies performed in the cerebrospinal fluid and during post-mortem analysis in
      parkinsonian patients revealed increased levels of cytokines, suggesting the
      activation of a proinflammatory response. Moreover, Langston and his group
      described the presence of active microglia in the SNpc of three patients who had
      been exposed to MPTP several years before death. These results suggested that the
      inflammatory response may increase negative feed-back into the damaged area of
      the cerebral parenchyma, inducing an imbalance that could perpetuate and/or
      accelerate neuronal death over a period of years. Similar results have been
      obtained in parkinsonian monkeys, rats and mice. For these reasons, several
      groups have treated parkinsonian animals with different anti-inflammatory drugs
      and obtained promising results. However, it is still not known whether
      inflammatory changes are responsible for active nerve cell death or whether they
      play a protective role in neurodegeneration. These changes are putatively related
      to neuronal loss and suggest that anti-inflammatory treatment for parkinsonian
      patients could have beneficial effects in the progression of the disease by
      slowing down the process of neuronal loss.

PMID- 14715445
TI  - Green tea polyphenol (-)-epigallocatechin-3-gallate protects rat PC12 cells from
      apoptosis induced by serum withdrawal independent of P13-Akt pathway.
AB  - Our recent studies have demonstrated that green tea polyphenol (-)
      epigallocatechin-3-gallate (EGCG) exerts neuroprotective/neurorescue effects
      against B-amyloid toxicity and protects neuronal cells from 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridinium ion (MPP+) and 6-hydroxydopamine in vitro, or from N
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced nigral dopaminergic
      neuronal loss in mice. In the present study, we report that EGCG (0.1 and 1
      microM) significantly protects rat pheochromocytoma PC12 cells from apoptosis
      induced by serum support withdrawal, suggesting that EGCG may play a role in the
      growth of PC12 cells, where it stimulates survival-promoting pathways.

PMID- 14715446
TI  - Cell culture protection and in vivo neuroprotective capacity of flavonoids.
AB  - Flavonoids are an important group of recognized antioxidants ubiquitous in
      fruits, vegetables and herbs. There are epidemiological evidences for the stroke
      protecting capacity of flavonoids and while the neuroprotective power of complex
      extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized
      red wine have been demonstrated in several studies, neuroprotection by individual
      flavonoids has been poorly studied in vivo. The neuroprotective capacity of
      individual flavonoids was studied in PC12 cells in culture and in a model of
      permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO). In
      the in vivo experiments, flavonoids were administered in lecithin preparations to
      facilitate the crossing of the blood brain barrier. The simultaneous incubation
      of PC12 cells with 200 micro M hydrogen peroxide (H2O2) and different flavonoids
      for 30 min resulted in a conspicuous profile: quercetin, fisetin, luteolin and
      myricetin significantly increased cell survival while catechin, kaempherol and
      taxifolin did not. Quercetin was detected in brain tissue 30 min and 1 h after
      intraperitoneal administration. When one of the protective flavonoids (quercetin)
      and one of those that failed to increase PC12 cell survival (catechin) were
      assessed for their protective capacity in the pMCAO model, administered i.p. 30
      min after vessel occlusion, quercetin significantly decreased the brain ischemic
      lesion while catechin did not. It is concluded that when administered in
      liposomal preparations, flavonoids structurally related to quercetin could become
      leads for the development of a new generation of molecules to be clinically
      effective in human brain ischemia.

PMID- 14715447
TI  - The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal
      neurons in hippocampal slice cultures from IL-1beta-induced neurodegeneration.
AB  - The neurotoxic effect of the pro-inflammatory cytokine interleukin (IL)-1beta was
      studied in monolayer cultures, obtained using roller-drum incubation of
      hippocampal slices from neonatal Sprague Dawley rats. Following exposure to
      recombinant rat IL-1beta for four days, a concentration dependent loss was
      observed in the number of NMDAR1 receptor subunit immunoreactive pyramidal
      neurons in the cultures, reaching significance at 10 ng/ml rIL-1beta. Also
      incubation with recombinant mouse IL-1beta caused a loss of pyramidal neurons,
      with a significant effect at a concentration of 30 pg/ml. The vitamin E analog
      trolox (30 microM) was found to exert a protective effect against the rIL-1beta
      induced neuronal degeneration. A neuroprotective action against rIL-1beta was
      also found after co-incubation with the NMDA antagonist dizocilpine (MK-801; 30
      microM), while no protection was found with the GABAA mimetic clomethiazole.
      Hence, the pro-inflammatory cytokine IL-1beta is neurotoxic to hippocampal
      pyramidal neurons when studied in an in vitro system with advanced phenotypic
      characteristics. The neuroprotective effects exerted by trolox and MK-801 suggest
      that free radicals and NMDA receptor-mediated processes are involved in IL-1beta 
      induced neurodegeneration.

PMID- 14715448
TI  - Effects of Sertoli cell transplants in a 3-nitropropionic acid model of early
      Huntington's disease: a preliminary study.
AB  - Problems with immunosuppression and graft survival limit clinical applications of
      neurotransplantation protocols for neurodegenerative disease. Sertoli cells,
      testes-derived cells with immunosuppressive and trophic properties, may serve as
      an alternative cell source for transplantation. Sertoli cells were transplanted
      into the striatum of rats following two injections of 3-nitropropionic acid (3
      NP) to determine whether they could ameliorate abnormalities in a model of early
      stage Huntington's disease. 3-NP-induced locomotor hyperactivity was
      significantly reduced in rats receiving Sertoli transplants compared to controls,
      with some behaviors returning to baseline. Sertoli cells survived in the striatum
      without systemic immunosuppression and some formed tubule-like structures. These
      results show that Sertoli transplants are able to ameliorate locomotor
      abnormalities in a 3-NP model of early HD. Thus, Sertoli cells should be further
      evaluated as a possible treatment strategy for the early stages of Huntington's
      disease.

PMID- 14715449
TI  - Paraquat and iron exposure as possible synergistic environmental risk factors in
      Parkinson's disease.

PMID- 14715450
TI  - Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar
      granule cells.
AB  - Alcoholism is associated with a higher incidence of smoking. In addition to the
      stimulatory effects of both ethanol and nicotine on the mesolimbic reward
      pathway, nicotine's ability to counteract some of the adverse effects of ethanol
      (e.g. ataxia) may be a powerful incentive for alcohol consumers to increase their
      tobacco (nicotine) intake. The cerebellum is believed to play an important role
      in ethanol-induced ataxia. In this study, we sought to test the hypothesis that
      nicotine would protect against toxic effects of ethanol in primary cultures of
      cerebellar granule cells. Moreover, it was postulated that the effects of
      nicotine would be mediated through nicotinic receptors. Primary cultures of
      cerebellar granule cells were prepared from 20-day embryos obtained from timed
      pregnant Sprague Dawley rats. Cells were cultured for 10 days and were then
      exposed for 3 days to various concentrations of ethanol with and without
      pretreatment with nicotine and nicotinic antagonists. Cellular toxicity was
      evaluated by measuring the lactate dehydrogenase level. Administration of ethanol
      (10-100 mM) resulted in a dose-dependent toxicity. Pretreatment with nicotine 1
      20 micro M resulted in a dose-dependent protection against ethanol-induced
      toxicity. The effects of nicotine were blocked by pretreatment with nicotinic
      antagonists such as mecamylamine 1-20 micro M, dihydro-beta-erythroidine 1.0 nM
      1.0 micro M and methyllycaconitine 5 nM-5 micro M in a dose-dependent manner.
      Thus, ethanol-induced cytotoxicity in primary cultures of cerebellar granule
      cells is blocked by pretreatment with nicotine. The effects of nicotine, in turn,
      may be blocked by nicotinic antagonists, implicating both high and low affinity
      nicotinic receptors in mediating the actions of nicotine. The exact mechanism of
      ethanol-induced toxicity and/or neuroprotection through activation of nicotinic
      receptors in this paradigm remains to be elucidated. The neuroprotective effect
      of nicotine against ethanol-induced toxicity in cerebellar neurons may be a
      contributing factor to the high incidence of smoking among alcoholics.

PMID- 14715451
TI  - Neuroprotection against Abeta and glutamate toxicity by melatonin: are GABA
      receptors involved?
AB  - The beta-amyloid peptide (Abeta) is centrally related to the pathogenesis of
      Alzheimer's disease (AD). Previous studies have suggested that the neurotoxicity
      of Abeta may be related to the overactivation of glutamatergic transmission and
      excitotoxicity, and that blockade of glutamate receptors prevents Abeta-induced
      cell death. Here, we show that melatonin, a pineal hormone, protects chick
      retinal neurons in culture against the neurotoxicity of Abeta and glutamate.
      Right-angle light scattering and thioflavin T fluorescence measurements, as well
      as light microscopy analysis, indicated that, under our experimental conditions,
      melatonin had no effect on the aggregation of Abeta. Interestingly, the
      neuroprotective action of melatonin against the toxicity of Abeta was
      significantly decreased in the presence of picrotoxin, an antagonist of GABA(A)
      like receptors. By itself, picrotoxin had no effect. These results suggest that
      the neuroprotective effects of melatonin against Abeta neurotoxicity could be at
      least in part related to a decrease in the excitatory tonus, mediated by
      activation of GABA receptors and the resulting hyper-polarization of the neurons.
      Thus, selective pharmacological manipulation of neuronal excitatory/inhibitory
      tonus could be a potentially interesting new approach in the treatment of AD.

PMID- 14715452
TI  - Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of
      locomotor activity in 6-hydroxydopamine-lesioned rats.
AB  - Repeated treatments with a dopamine (DA) D2 receptor agonist results in the
      induction of DA D2 receptor supersensitivity, as evidenced by enhanced behavioral
      responses to subsequent D2 agonist treatments - a phenomenon known as priming of
      receptors. Priming of D2 receptors has been well-studied in otherwise intact (non
      lesioned) rats. In contrast to D2 priming, repeated treatments with a DA D1
      agonist are unable to prime D1 receptors unless nigrostriatal DA fibers are
      largely destroyed in early postnatal ontogeny. In order to determine if D2
      receptors could be primed in rats in which nigrostriatal DA fibers were largely
      destroyed in early postnatal ontogeny, rats were (a) lesioned at 3 days after
      birth with 6-hydroxydopamine (67 micrograms in each lateral ventricle;
      desipramine, 20 mg/kg IP, 1 h; 6-OHDA), (b) treated daily for the first 28 days
      after birth with the D2 agonist quinpirole HCl (3.0 mg/kg IP), and (c) observed
      in adulthood for both quinpirole-induced and SKF 38393- (D1 agonist-) induced
      locomotor activity and stereotyped activities. In 6-OHDA-lesioned rats in which
      endogenous striatal DA was reduced by 99%, quinpirole did not produce enhanced
      locomotor or stereotyped activities. However, SKF 38393 produced increased
      locomotor and stereotyped activities even after the first dose of SKF 38393.
      These findings demonstrate that D2 receptors are not primed by ontogenetic
      quinpirole treatments of neonatally 6-OHDA-lesioned rats, although D2 agonist
      treatments do at least partially prime D1 receptors in the 6-OHDA-lesioned rats.

PMID- 14715453
TI  - Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced
      hippocampal damage.
AB  - The interactions of glia and neurons during injury and subsequent
      neurodegeneration are a subject of interest both in disease and chemical-induced
      brain injury. One such model is the prototypical hippocampal toxicant
      trimethyltin (TMT). An acute injection of TMT (2.0 mg/kg, i.p.) to postnatal day
      21 CD-1 male mice produced neuronal necrosis and loss of dentate granule cells,
      astrocyte hypertrophy, and microglia activation in the hippocampus within 24 hrs.
      Neuronal necrosis and microglia differentiation to a phagocytic phenotype is
      temporally correlated with peak elevations in TNF-alpha, cyclin A2, cyclin B1 and
      cyclin D1 at 72 h post-TMT. TNF-alpha mRNA levels were significantly elevated in
      the hippocampus by 12 h and remained elevated for 72 h. mRNA levels for cyclin A2
      and cyclin B1 were elevated by approximately 2-fold at 72 h. Immunohistochemistry
      suggested a cellular localization of cyclin A to microglia in the region of
      neuronal necrosis in the dentate, cyclin B in glial cells in juxtaposition to
      neurons in the hilus of the hippocampus and cyclin D1 to non-glial cells in the
      dentate. mRNA levels for cyclin D1 were elevated approximately 1.5-fold by 72 h
      as determined by RNase protection assay. No changes were seen in mRNA levels for
      cyclins E, F, G1, G2, H or I nor cyclin dependent kinases. These elevations are
      not associated with proliferation of microglia as determined by BrdU
      incorporation and Ki-67 immunohistochemistry. Upregulation of cell cycle genes
      was associated with cellular processes other than proliferation and may
      contribute to the differentiation of microglia to a phagocytic phenotype. These
      data suggest an integrated role for cell cycle regulation of neural cells in the
      manifestation of hippocampal pathophysiology.

PMID- 14715455
TI  - Corticosterone down-regulates dopamine D4 receptor in a mouse cerebral cortex
      neuronal cell line.
AB  - We have previously reported that restraint stress applied to the gestant mother
      results in long-lasting effects in the offspring that show an increase in the
      number of dopamine D2-type receptors in limbic areas on the adult rat brain
      cortex. Evidence that stress during pregnancy results in activation of the
      hypothalamic-pituitary-adrenal (HPA) axis has been extensively demonstrated.
      Therefore, high levels of corticosterone secreted in response to stress by the
      gestant mother might be one of the predisposing factors for the changes observed
      in dopamine receptors in the adult rat brain. In this study we addressed the
      question whether corticosterone would directly up-regulate D2-type receptors in
      vitro. We have investigated the effect of different concentrations of
      corticosterone on D4 dopamine receptor in immortalized cell lines from cerebral
      cortex of normal mouse fetuses, detected by immunocytochemistry employing
      polyclonal antibodies generated against synthetic peptides homologous to an
      extracellular domain of D4 receptor. The results show that corticosterone in
      vitro decreases the number of dopamine D4 receptors, suggesting that the increase
      of D2-type receptors in adult rats following prenatal stress is not related to a
      direct action of corticosterone on receptor expression.

PMID- 14715454
TI  - Human umbilical cord blood (HUCB) cells for central nervous system repair.
AB  - Cellular therapy is a compelling and potential treatment for certain neurological
      and neurodegenerative diseases as well as a viable treatment for acute injury to
      the spinal cord and brain. The hematopoietic system offers alternative sources
      for stem cells compared to those of fetal or embryonic origin. Bone marrow
      stromal and umbilical cord cells have been used in pre-clinical models of brain
      injury, directed to differentiate into neural phenotypes, and have been related
      to functional recovery after engraftment in central nervous system (CNS) injury
      models. This paper reviews the advantages, utilization and progress of human
      umbilical cord blood (HUCB) cells in the neural cell transplantation and repair
      field.

PMID- 14715456
TI  - Effects of alpha-adrenoceptor agonists in chronic morphine administered DSP4
      treated rats: evidence for functional cross-sensitization.
AB  - Five experiments were performed to study the effects of the Alpha-adrenoceptor
      agonists, clonidine and guanfacine, upon spontaneous motor activity in
      chronically morphine administered DSP4-treated and control rats. DSP4 (2 x 50
      mg/kg, with a 10-day interval between injections) and vehicle (distilled water)
      were injected i.p., on each occasion 30 min after zimeldine (20 mg/kg). Morphine
      dosages were raised incrementally from 5 mg/kg (Days 1-3), through 10 mg/kg (Days
      4-7) and 20 mg/kg (Days 8-14), to 30 mg/kg (Days 15-20). Motor activity testing
      occurred on Day 21, Day 22 as well as in Experiments II-V, (from 1st morphine
      injection). DSP4 pretreatment and chronic morphine injections each reduced motor
      activity during the first 30 min of testing; combined DSP4 and morphine treatment
      potentiated the hypoactivity. Habituation quotients indicated deficits in
      habituation to the novel test environment by the Vehicle-morphine (Quoteint2
      only) and DSP4-morphine groups. Acute clonidine treatment (0.04 mg/kg s.c.)
      reduced motor activity during the first 30 min of testing but attenuated or
      blocked the morphine-induced hypoactivity in DSP4-treated and control rats.
      During the 60-90 min test period, clonidine, but not guanfacine (0.08 mg/kg),
      potentiated morphine-induced hyperactivity in control rats; acute clonidine
      enhanced this effect, whereas acute guanfacine reduced it, in the DSP4-treated
      rats. The enhanced hyperactivity of morphine-clonidine suggest a cross
      sensitivity effect. Naloxone (0.1 mg/kg s.c.), injected after the 1st 30-min of
      testing, potentiated markely the clonidine-induced elevations of motor activity
      in morphine-administered control rats; in the DSP4-treated rats, these effects
      were dramatically potentiated, underlining the cross-sensitivity effect. Acute
      guanfacine treatment reduced motor activity during the first 30 min of testing
      but did not attenuate reliably morphine-induced hypoactivity in control or DSP4
      rats. Naloxone did not potentiate the guanfacine-induced hyperactivity of
      morphine-administered control rats but induced a marked enhancement in the DSP4
      treated rats, a specific case of cross-reactivity. The major findings pertain to
      a cross-sensitization effect of morphine upon clonidine-induced motor activity in
      both DSP4-treated and control rats, and to a lesser extent between morphine and
      guanfacine in NA-denervated rats only. The results may offer interactive
      implications for noradrenergic-opiate system functioning that may be of influence
      under neuropathological conditions.

PMID- 14715457
TI  - The dopamine D3 receptor and drug addiction.
AB  - Hedonic and reinforcing properties of drugs of abuse are closely related to brain
      dopamine neuron activity. All these drugs increase dopamine release in the shell
      of the nucleus accumbens, a brain region in which neurons co-express the D1 (D1R)
      and D3 (D3R) dopamine receptor subtypes, that converging pharmacological, human
      post-mortem and genetic studies suggest to be implicated in drug addiction. The
      D3R through a cross-talk with the D1R, is involved in induction and expression of
      behavioral sensitization to levodopa in rats bearing unilateral lesions of
      dopamine neurons. Behavioral sensitization, a cardinal feature of addiction
      arises from repeated administration of drugs of abuse thought to play a role in
      intensification of reinforcing efficacy of these drugs observed under certain
      conditions. Stimulation of the D3R also appears to enhance the reinforcing effect
      of cocaine in rats. By interacting with these processes, D3R agents have
      potential therapeutic applications for treating drug addiction. BP 897 (N-[4-(4
      (2-methoxyphenyl)piperazin-1-yl) butyl] naphtalen 2-carboxamide dichlorhydrate),
      a partial and highly selective D3R agonist in vitro, behaves as an agonist or an
      antagonist in vivo depending on the response considered. BP 897 has the
      unprecedented property to reduce cocaine-seeking behavior induced by presentation
      of a cocaine-associated cue, without having any intrinsic reinforcing effect. As
      drug-associated cues maintain drug-seeking in animals and elicit craving and
      relapse in humans, D3R agents like BP 897 may represent new medications for drug
      addiction, with minimal liability to maintaining dependence.

PMID- 14715458
TI  - HIV-1 infected and immune competent mononuclear phagocytes induce quantitative
      alterations in neuronal dendritic arbor: relevance for HIV-1-associated dementia.
AB  - Neuronal loss, alterations in dendritic arbor, and decreased synaptic density, in
      infected brain tissue, are neuropathological signatures of HIV-1-associated
      dementia (HAD). Brain mononuclear phagocyte (MP) (macrophage and microglia)
      secretory products can effect neuronal compromise, although the underlying
      mechanism(s) remain incompletely defined. To these ends, we quantitatively
      assessed the effects of virus-infected and/or immune activated MP secretory
      products on multiple aspects of neuronal morphology. Rat cortical and hippocampal
      neurons were exposed to secretory products from HIV-1-infected and
      lipopolysaccharide (LPS)-activated human monocyte-derived macrophage (MDM). Our
      assays for alterations in neuronal dendritic arbor and cell loss included the
      quantification of neurofilament (NF), neuron-specific enolase (NSE), and MAP-2 by
      ELISA and cellular morphology. MDM conditioned media (MCM) enhanced neuronal
      survival. HIV-1 infection or activation by LPS had modest neurotoxic effects. In
      contrast, the combination of HIV-1 infection and activation of MDM produced
      significant neurotoxicity. Such MDM products altered dendritic arbor, decreased
      synaptic density, and increased LDH release. Comparable neurotrophic/toxic
      responses were observed when neurons were exposed to MCM collected from 12
      separate human donors. Similar responses were observed with MCM from human fetal
      microglia, further supporting the role of HIV-1-infected and immune-activated
      brain MP in the overall neurotoxic responses. This work provides quantitative
      measures of neuronal damage by which virus infected and activated MP can elicit
      neuronal injury in HAD.

PMID- 14715459
TI  - HIV-1 infected immune competent mononuclear phagocytes influence the pathways to
      neuronal demise.
AB  - Secretory products from HIV-1-infected immune-competent mononuclear phagocytes
      (MP) damage neuronal dendritic arbor (Zheng et al., 2001). The mechanism behind
      neuronal injury and whether it is species and/or viral strain dependent is not
      fully understood. To these ends, we investigated whether HIV-1-infected and
      lipopolysaccharide (LPS)-activated MDM elicit neuronal injury in primary human
      neurons. Neuronal damage was compared to that seen in rat neurons. Utilizing a
      spectrum of HIV-1 strains to infect human monocyte-derived macrophages (MDM),
      productive viral replication proved necessary, but not sufficient, for neuronal
      injury. Neuronal demise was induced by virion-free HIV-1-infected and immune
      activated MDM culture supernatants. Maximal alterations in glutamate mediated
      neuronal signaling, resulted from exposure to secretory products from HIV-1
      infected and immune-activated MDM. Apoptosis was the predominant mechanism of
      cell death induced by HIV-1-infected and LPS-treated MDM. Importantly, neuronal
      injury and increases in calcium influx mediated by HIV-1-infected and immune
      activated MDM culture supernatants was partially blocked by the N-methyl D
      aspartate (NMDA) receptor antagonist, MK 801. These data support a primary role
      for immune-activation in MP neurotoxic activities. The upregulation of NMDA
      receptor sensitive soluble factors and neuronal apoptosis by HIV-1-infected and
      immune-activated MDM provide unique insights into links between soluble factors,
      produced as a consequence of MP immunity, and neuronal demise in HAD.

PMID- 14715460
TI  - The common neurotrophin receptor p75NTR enhances the ability of PC12 cells to
      resist oxidative stress by a trkA-dependent mechanism.
AB  - Functional role(s) for the common neurotrophin receptor p75NTR in nerve growth
      factor (NGF) signaling have yet to be fully elucidated. Many studies have
      demonstrated that p75NTR can enhance nerve growth factor-induced survival
      mediated via the trkA receptor. In addition, newly identified pathways for p75NTR
      signaling have included distinct p75NTR-specific and trk-independent effects
      which generally appear to be pro-apoptotic. In the present study, we have
      examined the influence of p75NTR on NGF-mediated protective effects from hydrogen
      peroxide (H2O2)-induced apoptotic cell death of PC12 cells. Exposure of PC12
      cells to H2O2 resulted in Caspase-3 activation and apoptosis. NGF protected PC12
      cells against H2O2-mediated apoptosis in a dose-dependent manner and inhibited
      Caspase-3 activation. These effects of NGF required activation of both PI 3
      kinase and MAP kinase signal pathways. When NGF binding to p75NTR was blocked by
      treating cells with either BDNF or PD90780, and where p75NTR expression was
      reduced by treating cells with antisense oligonucleotide to p75NTR, the
      protective effects of NGF were attenuated. Further, NGF had no effect on cell
      viability in PC12nn5 cells, which express only p75NTR. When trk-mediated signal
      transduction was blocked, leaving p75NTR signaling activated, PC12 cells were not
      more vulnerable to H2O2. These data suggest that p75NTR enhances the ability of
      PC12 cells to resist oxidative stress by a trkA-dependent mechanism, potentially
      by allosteric mechanisms. Further, potential trkA-independent and pro-apoptotic
      signaling of p75NTR does not contribute to apoptotic cell death of PC12 cells in
      a setting of oxidative insult.

PMID- 14715461
TI  - Apoptotic morphology does not always require caspase activity in rat cerebellar
      granule neurons.
AB  - The death of a cell via apoptosis is characterized by morphological changes
      including cell shrinkage and nuclear condensation. Intracellularly, proteases,
      including caspases, are activated. In the present article we have compared the
      ability of three different neurotoxic agents to induce caspase activity in
      cerebellar granule cells (CGC). These compounds are the microtubule-disrupting
      agent colchicine and the oxidative stress-inducing agents hydrogen peroxide and
      methylmercury (MeHg). We have previously shown that each of these agents causes
      nuclear changes that are consistent with apoptosis, i.e., induction of chromatin
      condensation and DNA cleavage into fragments of regular size (700, 300 and 50
      kbp). However, only colchicine causes a large increase in caspase activity, as
      monitored by the ability of whole cell extracts to cleave the synthetic caspase
      substrate DEVD-MCA. In contrast, MeHg and hydrogen peroxide do not induce any
      significant increase of DEVDase activity as compared to control cells.
      Immunocytochemistry confirms that active caspase-3 is abundant only in colchicine
      exposed cells. In agreement with these findings, the pan-caspase inhibitor, z-VAD
      fmk, is efficient in protecting CGC against colchicine, but not against hydrogen
      peroxide or MeHg. These data suggest that in CGC the activation of caspases is
      not always required to induce morphological changes and pattern of DNA
      fragmentation consistent with apoptosis.

PMID- 14715463
TI  - In vitro metabolism of chlorpromazine by cytochromes P450 4F4 and 4F5 and the
      inhibitory effect of imipramine.
AB  - The metabolism of chlorpromazine by expressed recombinant cytochromes P450 4F4
      and 4F5 cloned from rat brain was analyzed to characterize the individual
      activities of the isoforms. Both isoforms metabolized chlorpromazine to both the
      N-demethylated and the S-oxide products. When isoforms were incubated with
      chlorpromazine in the presence of increasing concentrations of imipramine,
      imipramine significantly inhibited both N-demethylation and S-oxidation of
      chlorpromazine. A dilution of the serum fraction of anti-4F antibody was also
      found to significantly inhibit both S-oxidation and N-demethylation of
      chlorpromazine by both 4F4 and 4F5.

PMID- 14715462
TI  - Pharmacological and toxicological significance of brain cytochromes P450.

PMID- 14715464
TI  - Identification, induction and localization of cytochrome P450s of the 3A
      subfamily in mouse brain.
AB  - Several cytochrome P450 subfamilies are inducible by specific exogenous compounds
      like the antiepileptic drug phenytoin. Some of these P450 enzymes are involved in
      the metabolism of gonadal hormones also contributing to neuronal differentiation.
      CYP3A enzymes have the capacity to catalyze the hydroxylation of testosterone and
      a wide variety of therapeutic agents, but little is known about the expression
      and potential function of this subfamily in mouse brain. Here, we report the
      identification of mouse CYP3A isoforms, their induction and localization in mouse
      brain. Western blot analysis with anti-CYP3A1 antibodies revealed the phenytoin
      inducible expression of CYP3A in brain microsomes, and also a constitutive
      expression of members of this subfamily in brain mitochondria. Using RT-PCR with
      a consensus primer pair for known mouse liver CYP3A-isoforms we could demonstrate
      the expression of CYP3A11 and 3A13 mRNA in mouse brain. Finally, using double
      immunofluorescence labeling we analyzed the histoanatomical distribution of CYP3A
      throughout the brain with confocal laser scanning microscopy. We found strong
      immunoreactivity in neurons of hippocampus and hypothalamic areas which are
      sensitive to steroid hormones. CYP3A immunoreactivity was apparent also in
      neurons of the cerebellum, the thalamus and the olfactory bulb. Non-neuronal
      expression of CYP3A could be found in some astrocyte populations and in vascular
      as well as ventricular border lines. The presence of CYP3A predominantly in
      neurons but also in cells contributing to the blood-brain and blood-liquor
      barrier suggests important roles of this subfamily in mediation of steroid
      hormone action in mouse brain as well as in preventing the brain from potentially
      cytotoxic compounds.

PMID- 14715465
TI  - Induction of rat brain cytochrome P450s (P450s) by deltamethrin: regional
      specificity and correlation with neurobehavioral toxicity.
AB  - Oral administration of 5 mg/kg body weight of deltamethrin, an alpha-cyano type
      II pyrethroid insecticide once a day for 1, 7, 15 and 21 consecutive days to
      young Druckerey rats (6- 8 weeks old) produced a time dependent increase in the
      activity of cytochrome P450 (P450) dependent 7-ethoxyresorufin-O-deethylase
      (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat brain microsomes. A
      significant induction was observed on prolonged exposure of deltamethrin for 15
      or 21 days. The induction in the activity of cerebral P450 enzymes was associated
      with the time dependent increase in the spontaneous locomotor activity indicating
      accumulation of deltamethrin or its metabolites in brain with the increase in the
      duration of exposure. Administration of deltamethrin (5 mg/kg) for 21 days
      produced region specific changes in the dealkylation of ethoxyresorufin and
      pentoxyresorufin in rat brain with significant induction occurring in the
      activity of P450 1A1/2 dependent EROD in cerebellum, hippocampus, hypothalamus
      and medulla-pons and that of P450 2B1/2 mediated PROD in hippocampus,
      hypothalamus, corpus striatum and mid brain. The data suggests that the
      differences in the induction of individual P450 isoenzymes in diverse brain
      regions could play a role in regulating the response of brain to pyrethroid
      insecticides by modulating their concentration per se or their active metabolites
      at the target site(s).

PMID- 14715466
TI  - Inhibition of rat brain microsomal cytochrome P450-dependent dealkylation
      activities by an oxidative stress.
AB  - There is increasing evidence that an oxidative stress not only alters cellular
      lipids and nucleic acids, but also numerous proteins. This oxidation results in
      alterations of some cellular functions, either by reversible modifications
      allowing a post-transcriptional regulation of enzyme activities or receptor
      affinities, or by irreversible modifications of the protein, triggering its
      inactivation and destruction. In the present work, we examined the effects of an
      experimental oxidative stress on rat brain microsomal cytochrome P450-dependent
      dealkylation activities. For that purpose, superoxide anions were produced either
      by the NADPH-dependent redox cycling of a quinine, menadione, or by the addition
      of apomorphine, which produces by autoxidation both superoxide anions and
      apomorphine-derived quinones. The inhibition of brain cytochrome P450-dependent
      alkoxyresorufin O-dealkylase activities was dependent on both menadione or
      apomorphine concentrations. Simultaneously, an increase of microsomal carbonyl
      groups was recorded. Immunoblotting characterization of brain microsomal oxidized
      protein was carried out, using antibodies raised against 2,4
      dinitrophenylhydrazine as a reagent of protein carbonyl groups, and a revelation
      by a chemiluminescence method. We observed an increase in cerebral CYP1A protein
      oxidation, related to menadione concentration, suggesting that oxidation of
      cytochrome P450 protein may result in its catalytic inactivation.

PMID- 14715467
TI  - Characterization and localization of cytochrome P450 mediated metabolism of MPTP
      to nor-MPTP in mouse brain: relevance to Parkinson's disease.
AB  - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is a dopaminergic toxin which
      produces Parkinson's disease-like symptoms in primates and dopaminergic cell loss
      in mice. MPTP is bioactivated through monoamine oxidase to MPP(+) and detoxified
      by cytochrome P450 to nor-MPTP. We have examined metabolisms of MPTP to nor-MPTP
      by mouse brain microsomes and compared it with corresponding activity in liver.
      In brain, but not in liver, this biotransformation was completely abolished by
      quinidine, an inhibitor of P4502D. Northern blotting experiments demonstrated
      constitutive expression of cytochrome P4502D mRNA predominantly in neuronal cells
      within the cortex, hippocampus, thalamus, Purkinje and granule cell layers of the
      cerebellum and in the reticular neurons of midbrain. Striatal neurons were
      sparsely stained indicating a relative paucity of expression. These studies
      demonstrate for the first time that detoxification of MPTP to nor-MPTP occurs in
      mouse brain through cytochrome P4502D which is primarily localized in neuronal
      cells. Cytochrome P4502D6 is known to exhibit genetic polymorphism in humans, and
      a defect in this isoform could potentially lead to decreased detoxification of
      neurotoxins in certain neuronal sub-population, which in turn may have
      implications in pathogenesis of Parkinson's disease.

PMID- 14715468
TI  - RS-100642-198, a novel sodium channel blocker, provides differential
      neuroprotection against hypoxia/hypoglycemia, veratridine or glutamate-mediated
      neurotoxicity in primary cultures of rat cerebellar neurons.
AB  - The present study investigated the effects of RS-100642-198 (a novel sodium
      channel blocker), and two related compounds (mexiletine and QX-314), in in vitro
      models of neurotoxicity. Neurotoxicity was produced in primary cerebellar
      cultures using hypoxia/hypoglycemia (H/H), veratridine or glutamate where, in
      vehicle-treated neurons, 65%, 60% and 75% neuronal injury was measured,
      respectively. Dose-response neuroprotection experiments were carried out using
      concentrations ranging from 0.1-500 micro M. All the sodium channel blockers were
      neuroprotective against H/H-induced injury, with each exhibiting similar potency
      and efficacy. However, against veratridine-induced neuronal injury only RS-100642
      198 and mexiletine were 100% protective, whereas QX-314 neuroprotection was
      limited (i.e. only 54%). In contrast, RS-100642-198 and mexiletine had no effect
      against glutamate-induced injury, whereas QX-314 produced a consistent, but very
      limited (i.e. 25%), neuroprotection. Measurements of intraneuronal calcium
      [Ca(2+)]i) mobilization revealed that glutamate caused immediate and sustained
      increases in [Ca(2+)]i which were not affected by RS-100642-198 or mexiletine.
      However, both drugs decreased the initial amplitude and attenuated the sustained
      rise in [Ca(2+)]i mobilization produced by veratridine or KCl depolarization. QX
      314 produced similar effects on glutamate-, veratridine- or KCl-induced [Ca(2+)]i
      dynamics, effectively decreasing the amplitude and delaying the initial spike in
      [Ca(2+)]i, and attenuating the sustained increase in [Ca(2+)]i mobilization. By
      using different in vitro models of excitotoxicity, a heterogeneous profile of
      neuroprotective effects resulting from sodium channel blockade has been described
      for RS-100642-198 and related drugs, suggesting that selective blockade of
      neuronal sodium channels in pathological conditions may provide therapeutic
      neuroprotection against depolarization/excitotoxicity via inhibition of voltage
      dependent Na(+) channels.

PMID- 14715469
TI  - Oxidative stress induces apoptosis in C6 glioma cells: involvement of mitogen
      activated protein kinases and nuclear factor kappa B.
AB  - Excessive oxidative stress has been implicated in the induction of cell death in
      a variety of neurodegenerative diseases. In the present study, hydrogen peroxide
      (H2O2)-induced cell death in rat C6 glioma cells was used as a model system for
      studying the molecular events associated with oxidative stress-induced cell death
      in glial cells. We demonstrate that exposure of C6 glioma cells to H2O2 results
      in apoptotic cell death in a concentration-dependent manner, and caused
      activation of a member of the caspase-3-like family of proteases resulting in
      cleavage of the DNA repair enzyme poly(ADP-ribose)polymerase, PARP. Furthermore,
      H2O2 induced a transient activation of the transcription factor, nuclear factor
      kappa B (NF(Kappa)B). Pre-treatment of cells with the antioxidant N
      acetylcysteine, (NAC), prevented both the activation of NF(Kappa)B and the
      induction of apoptosis by H2O2, suggesting a possible role for this transcription
      factor in oxidant-induced apoptosis in glial cells. Exposure of the cells to H2O2
      led to transient activation of both c-Jun N-terminal kinase (JNK) and p38 kinase
      but has no effect on extracellular regulated kinase (ERK) activity. Inhibition of
      p38 by SB203580 did not protect the cells against H2O2-induced apoptosis
      suggesting that activation of p38 is not essential for H2O2-mediated cell death
      in C6 glioma cells.

PMID- 14715470
TI  - The possible role of one-electron reduction of aminochrome in the
      neurodegenerative process of the dopaminergic system.
AB  - We present for discussion a possible molecular mechanism explaining the formation
      of reactive oxygen species involved in the neurodegenerative process of
      dopaminergic system in Parkinson's disease. This new hypothesis involves one
      electron reduction of aminochrome to o-semiquinone radical, which seems to be the
      reaction responsible for neurodegenerative process of dopaminergic system.
      Leukoaminochrome o-semiquinone is extremely reactive with oxygen, which
      reoxidizes by reducing oxygen to superoxide radicals. Superoxide radicals
      enzymatically or spontaneously dismutate to dioxygen and hydrogen peroxide which
      is a precursor of hydroxyl radicals. ESR-experiments have showed that aminochrome
      o-semiquinone is extremely reactive in the presence of oxygen compared to
      dopamine o-semiquinone. In addition, the antioxidant enzymes superoxide dismutase
      and catalase play a prooxidant role by increasing the autoxidation rate and
      formation of superoxide radicals. One electron reduction of aminochrome to o
      semiquinone can be performed by flavoenzymes which use NADPH and NADH as electron
      donator. The ability of aminochrome o-semiquinone to autoxidize in the presence
      of oxygen gives rise to a redox cycling process which will continue until oxygen,
      NADH and/or NADPH are depleted. Depletion of NADPH will prevent glutathione
      reductase from reducing glutathione, which is one of the main antioxidants in the
      cell. In addition depletion of NADH will prevent the formation of ATP in the
      electron transport chain in the mitochondria. Two antioxidants, probably,
      neuroprotective reactions are also discussed.

PMID- 14715471
TI  - Oxidized lipoproteins, beta amyloid peptides and Alzheimer's disease.
AB  - Recent studies have provided strong evidence for the involvement of oxidative
      stress in the pathogenesis of Alzheimer's disease (AD) and beta-amyloid peptides
      (ABeta) have been implicated to play an important role in mediating these
      oxidative events. Lipoproteins (LP) in the brain are likely targets of oxidative
      insult and together enhance ABeta -mediated toxicity to neurons. We hypothesize
      that uptake of oxidized LP by neuron leads to an acceleration of the
      intracellular oxidative pathways and exacerbation of neuron cell death. In our
      previous studies, we demonstrated the ability of oxidized low-density LP from
      plasma to induce cell death in PC12 cells. In this study, a synthetic LP fraction
      was prepared using lipids extracted from rat brain and incubated with albumin and
      apoE. This brain lipid-derived LP (BLP) was subjected to oxidation by incubation
      with Fe(3+)and subsequently tested with primary cortical neurons in culture. To
      study uptake of the BLP, native and oxidized BLP containing apoE3 or apoE4 were
      labeled with [(14)C]cholesterol or the fluorescent probe 3,3-dioctadecylindo
      carbocyanine (Di-I) prior to exposing to cultured neurons. Results showed that
      regardless of the labeling method, oxidized BLP were more effectively taken up by
      the neurons than the native BLP. Cell viability was assessed by assaying the
      release of lactate dehydrogenase (LDH) into the medium and by determining the
      reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),
      an agent depicting mitochondrial activity. While exposure of neurons to oxidized
      BLP and aggregated ABeta (1-42) alone could result in MTT reduction (24%),
      greater reduction (40%) could be observed when oxidized LP was added together
      with ABeta. Neuronal cell death due to oxidized BLP could be ameliorated by
      resveratrol, a polyphenolic compound known for its antioxidant properties. Taken
      together, these results are in agreement with the notion that ABeta and oxidized
      BLP can synergistically enhance oxidative damage in neurons and antioxidants such
      as resveratrol can ameliorate these damages.

PMID- 14715472
TI  - Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death.
AB  - Glutamate is the main excitatory neurotransmitter in mammals. However, excessive
      activation of glutamate receptors is neurotoxic, leading to neuronal degeneration
      and death. In many systems, including primary cultures of cerebellar neurons,
      glutamate neurotoxicity is mainly mediated by excessive activation of NMDA
      receptors, leading to increased intracellular calcium which binds to calmodulin
      and activates neuronal nitric oxide synthase (NOS), increasing nitric oxide (NO)
      which in turn activates guanylate cyclase and increases cGMP. Inhibition of NOS
      prevents glutamate neurotoxicity, indicating that NO mediates glutamate-induced
      neuronal death in this system. NO generating agents such as SNAP also induce
      neuronal death. Compounds that can act as "scavengers" of NO such as Croman 6 (CR
      6) prevent glutamate neurotoxicity. The role of cGMP in the mediation of
      glutamate neurotoxicity remains controversial. Some reports indicate that cGMP
      mediates glutamate neurotoxicity while others indicate that cGMP is
      neuroprotective. We have studied the role of cGMP in the mediation of glutamate
      and NO neurotoxicity in cerebellar neurons. Inhibition of soluble guanylate
      cyclase prevents glutamate and NO neurotoxicity. There is a good correlation
      between inhibition of cGMP formation and neuroprotection. Moreover 8-Br-cGMP, a
      cell permeable analog of cGMP, induced neuronal death. These results indicate
      that increased intracellular cGMP is involved in the mechanism of neurotoxicity.
      Inhibitors of phosphodiesterase increased extracellular but not intracellular
      cGMP and prevented glutamate neurotoxicity. Addition of cGMP to the medium also
      prevented glutamate neurotoxicity. These results are compatible with a neurotoxic
      effect of increased intracellular cGMP and a neuroprotective effect of increased
      extracellular cGMP.

PMID- 14715473
TI  - Reactive oxygen species, apoptosis and altered NGF-induced signaling in PC12
      pheochromocytoma cells cultured in elevated glucose: an in vitro cellular model
      for diabetic neuropathy.
AB  - Diabetic neuropathies, affecting the autonomic, sensory, and motor peripheral
      nervous system, are among the most frequent complications of diabetes. The
      symptoms of diabetic polyneuropathies are multi-faceted; the etiology and the
      underlying mechanisms are as yet unclear. Clinical studies established a
      significant correlation between the control of the patients' blood glucose level
      and the severity of the damage to the peripheral nervous system. Recent in vitro
      studies suggest that elevated glucose levels induced dysfunction and apoptosis in
      cultured cells of neuronal origin, possibly through the formation of reactive
      oxygen species (ROS). Based on these results, we hypothesized that elevated
      glucose levels impair neuronal survival and function via ROS dependent
      intracellular signaling pathways. In order to test this hypothesis, we cultured
      neural crest-derived PC12 pheochromocytoma cells under euglycemic (5 mM) and
      hyperglycemic (25 mM) conditions. Continuous exposure of undifferentiated PC12
      cells for up to 72 h to elevated glucose induced the enhanced generation of ROS,
      as assessed from the increase in the cell-associated fluorescence of the ROS
      sensitive fluorogenic indicator, 2,7-dichlorodihydrofluorescein diacetate. In
      cells cultured in high glucose, both basal and secretagogue-stimulated
      catecholamine release were enhanced. Furthermore, high glucose, reduced (by ca.
      30%) the rate of cell proliferation and enhanced the occurrence of apoptosis, as
      assessed by DNA fragmentation, TUNEL assay and the activation of an apoptosis
      specific protease, caspase CCP32. Elevated glucose levels significantly
      attenuated nerve growth factor (NGF)-induced neurite extension, as quantitated by
      computer-aided image analysis. Culturing PC12 cells in high glucose resulted in
      alterations in basal and NGF-stimulated mitogen-activated protein kinase (MAPK)
      signaling pathways, specifically in a switch from the neuronal
      survival/differentiation-associated MAPK ERK to that of apoptosis/stress
      associated MAPK p38 and JNK. Based on our results we present a model in which the
      prolonged, excess formation of ROS represents a common mechanism for
      hyperglycemia-induced damage to neuronal cells. We propose that this simple in
      vitro system might serve as an appropriate model for evaluating some of the
      effects of elevated glucose on cultured cells of neuronal origin.

PMID- 14715475
TI  - Peroxisome proliferator-activated receptor-gamma agonist increases both low
      density lipoprotein cholesterol particle size and small high-density lipoprotein
      cholesterol in patients with type 2 diabetes independent of diabetic control.
AB  - OBJECTIVE: To ascertain whether troglitazone, independent of control of diabetes,
      increases low-density lipoprotein (LDL) particle size. METHODS: We administered
      600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma
      agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom
      completed the study). Then troglitazone therapy was discontinued, and alternative
      medication for diabetic control was used for another 4 weeks. The LDL, very-low
      density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and
      subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were
      determined at weeks 0, 4, 8, and 12 and analyzed statistically. RESULTS: Small,
      dense LDL cholesterol is commonly seen in patients with diabetes and is thought
      to be associated with an increased risk for coronary artery disease. After both 4
      and 8 weeks of troglitazone therapy, control of diabetes was significantly
      improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%,
      7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12
      weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9
      mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone
      therapy was discontinued. Troglitazone treatment increased the large LDL particle
      at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle
      size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4,
      and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL
      triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and
      HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This
      greater HDL value was due to an increase in the small HDL particles. A decrease
      in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL
      particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that
      control of diabetes remained significantly improved after troglitazone therapy
      was discontinued, the LDL particle size decreased to the baseline value. This
      change was due to a reduction in the large LDL cholesterol particle (L3).
      CONCLUSION: This study shows that troglitazone therapy increases LDL particle
      size, reduces VLDL particle size, and increases small HDL particles. These
      changes may lower the risk for coronary artery disease.

PMID- 14715474
TI  - Role of astrocytes in pathogenesis of ischemic brain injury.
AB  - Astrocytes play an important role in the homeostasis of the CNS both in normal
      conditions and after ischemic injury. The swelling of astrocytes is observed
      during and several seconds after brain ischemia. Then ischemia stimulates
      sequential morphological and biochemical changes in glia and induces its
      proliferation. Reactive astrocytes demonstrate stellate morphology, increased
      glial fibrillary acidic protein (GFAP) immunoreactivity, increased number of
      mitochondria as well as elevated enzymatic and non-enzymatic antioxidant
      activities. Astrocytes can re-uptake and metabolize glutamate and in this way
      they control its extracellular concentration. The ability of astrocytes to
      protect neurons against the toxic action of free radicals depends on their
      specific energy metabolism, high glutathione level, increased antioxidant enzyme
      activity (catalase, superoxide dismutase, glutathione peroxidase) and
      overexpression of antiapoptotic bcl-2 gene. Astrocytes produce cytokines (TNF
      alpha, IL-1, IL-6) involved in the initiation and maintaining of immunological
      response in the CNS. In astrocytes, like in neurones, ischemia induces the
      expression of immediate early genes: c-fos, c-jun, fos B, jun B, jun D, Krox-24,
      NGFI-B and others. The protein products of these genes modulate the expression of
      different proteins, both destructive ones and those involved in the
      neuroprotective processes.

PMID- 14715476
TI  - Clinical management of primary hyperparathyroidism and thresholds for surgical
      referral: a national study examining concordance between practice patterns and
      consensus panel recommendations.
AB  - OBJECTIVE: To determine whether 1990 guidelines established by the National
      Institutes of Health (NIH) for the optimal management (surgical versus
      nonsurgical) of patients with asymptomatic primary hyperparathyroidism (PHPT) are
      known and followed by endocrinologists. METHODS: We surveyed endocrinologists in
      the United States who were randomly selected in 1998 from two endocrine
      societies. Endocrinologists were asked about management of asymptomatic patients
      with PHPT, awareness of NIH recommendations, practice demographics, and annual
      PHPT case volume. We classified endocrinologists into either low-volume (<12
      cases of PHPT per year) or high-volume (> or = 12 cases per year) physicians.
      RESULTS: Of 374 eligible physicians, 146 (39%) responded to our survey. In
      comparison with nonrespondents, respondents were of similar age, sex, years in
      practice, and geographic location profiles; this finding suggested minimal
      nonresponse bias. More high-volume physicians than low-volume physicians were
      aware of the NIH guidelines (75% versus 50%; P<0.01). Management of asymptomatic
      patients was similar between volume groups; overall, 39% of patients were
      referred for surgical treatment. Nevertheless, considerable variation in
      management existed; 7% of all physicians referred > or = 90% of their
      asymptomatic patients for surgical treatment, whereas 31% referred < or = 10%.
      Adherence to monitoring guidelines for nonsurgically managed patients ranged
      widely, depending on the specific recommendation (from 6% of physicians obtaining
      creatinine clearance assessments every 6 months to 78% of physicians ordering
      serum calcium measurements every 6 months). Surgical referral practices also
      varied substantially, with 25% of all physicians referring a 40-year-old patient
      with PHPT when hypercalcemia was mild (< or = 1 mg/dL above normal), 39% when
      hypercalcemia was moderate, and 31% when hypercalcemia was severe (>1.5 mg/dL
      above normal). Of the responding physicians, 4% reported that hypercalcemia alone
      was not sufficient justification to refer a patient for surgical intervention.
      Higher PHPT case volume was not associated with differences in surgical referral.
      CONCLUSION: Suboptimal awareness of the 1990 NIH panel recommendations and the
      substantial variation in clinical management of PHPT indicate that newer NIH
      guidelines developed in 2002 must be more widely disseminated and strongly
      recommended if practice patterns are to be influenced and clinical outcomes
      improved.

PMID- 14715477
TI  - Cost analysis of different screening strategies for gestational diabetes
      mellitus.
AB  - OBJECTIVE: To analyze the findings of a survey in Tehran, Iran, to determine the
      screening method for gestational diabetes mellitus (GDM) best suited to the local
      population. METHODS: In four university teaching hospitals in Tehran, 2,416
      pregnant women were classified into high-, intermediate-, and low-risk groups, on
      the basis of criteria established by the American Diabetes Association, and then
      screened for GDM. A two-step approach was implemented, with use of blood glucose
      thresholds of 130 mg/dL and 140 mg/dL and the previously advocated diagnostic
      criteria of two or more abnormal results of an oral glucose tolerance test.
      RESULTS: The prevalence of GDM is increasing globally, and the major determinants
      of screening programs for GDM are the cost-to-benefit ratio and the prevalence in
      the target population. The prevalence of GDM in our study sample was 4.7%.
      Changing from the 130 mg/dL to the 140 mg/dL blood glucose threshold decreased
      case-detection sensitivity by 12%, to 88%. With this approach, however, the cost
      of screening for GDM per pregnancy decreased from US dollars 3.80 to US dollars
      3.21 (-15.5%), and the cost per detected case of GDM declined from US dollars
      80.56 to US dollars 77.44 (-3.9%). CONCLUSION: We recommend universal screening
      for GDM in populations, such as ours, that have a substantial baseline prevalence
      of GDM and variable health-care coverage. In such a setting, a considerable
      proportion of cases of GDM may be missed. Moreover, universal screening is less
      expensive in developing countries than in more developed economies and leads to
      clearer long-term savings for a health service stretched to the limit.

PMID- 14715478
TI  - Risk of malignancy in follicular neoplasms without nuclear atypia: statistical
      analysis of 397 thyroidectomies.
AB  - OBJECTIVE: To determine how to triage patients with a follicular neoplasm (FN),
      without nuclear atypia reported by fine-needle aspiration, on the basis of risk
      factors. METHODS: The age, sex, tumor size, and cell type of 397 patients who
      underwent thyroidectomy for follicular carcinoma (FC) or follicular adenoma
      between 1991 and 2001 were analyzed statistically. The likelihood ratio and
      probability of FC for various combinations of tumor size, sex, and cell type were
      estimated with use of Bayes' theorem. RESULTS: FC was significantly associated
      with tumor size >2.1 cm (P = 0.048), male sex (P = 0.0007), and Hurthle cell type
      (P<0.0001). The mean size of minimally invasive FC was significantly smaller (2.9
      cm versus 4.8 cm; P = 0.004) and the mean patient age was significantly younger
      (47.6 years versus 61.0 years; P = 0.003) than for widely invasive FC. The lowest
      probability (0.31%) for FC was in female patients with a small (< or = 2.1 cm)
      micro-follicular FN reported by a cytopathology practice with 10% accuracy of
      true FN at surgical intervention, whereas the highest probability (29.5%) for FC
      was in male patients with a large (>2.1 cm) Hurthle cell neoplasm reported by a
      cytopathology practice with 70% accuracy of true FN at surgical intervention.
      CONCLUSION: Although an estimate of probability for FC based on age, sex, thyroid
      nodule size, and cell type is provided in this study for patients diagnosed with
      FN without nuclear atypia on fine-needle aspiration, the variability of the
      accuracy in cytopathology practice makes it difficult to change the current
      treatment paradigm, which requires carefully planned prospective studies with
      long-term follow-up.

PMID- 14715479
TI  - Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone,
      and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis.
AB  - OBJECTIVE: To present two cases of hypercalcemia associated with thyrotoxicosis
      and to describe serial biochemical findings during the course of treatment of
      hyperthyroidism. METHODS: We report two cases, illustrate the changes in serum
      calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during
      management of thyrotoxicosis, and compare our findings with those in previous
      studies. RESULTS: Hypercalcemia attributable to thyrotoxicosis is well
      documented, but the mechanism for the hypercalcemia is incompletely understood.
      Our first patient had a complicated medical history and several potential causes
      of hypercalcemia, including recurrent hyperparathyroidism, metastatic breast
      cancer, and relapse of previously treated thyrotoxicosis. A suppressed
      parathyroid hormone level and negative bone and computed tomographic scans
      excluded the first two factors. After thyroid ablation with 131I, the serum
      calcium and thyroxine levels decreased, and the parathyroid hormone and 1,25
      dihydroxyvitamin D3 levels normalized. Our second patient, who was referred to
      our institution with a preliminary diagnosis of hypercalcemia associated with
      malignant disease and who had no symptoms of hyperthyroidism, was found to have a
      high free thyroxine level, diffuse enlargement of the thyroid, and high uptake
      (58%) of 123I on a thyroid scan. After thyroid ablation, the serum calcium, 1,25
      dihydroxyvitamin D3, and intact parathyroid hormone levels normalized, and the
      free thyroxine level declined. The probable pathogenesis of hypercalcemia in
      thyrotoxicosis is reviewed with respect to thyroid hormone and its effect on bone
      turnover. CONCLUSION: Physicians should consider thyrotoxicosis in the
      differential diagnosis of hypercalcemia.

PMID- 14715480
TI  - Metachronous double parathyroid adenomas involving two different cell types:
      chief cell and oxyphil cell.
AB  - OBJECTIVE: To describe a patient with the rare occurrence of metachronous double
      parathyroid adenomas involving two different cell types. METHODS: We present a
      case report and a summary of the related literature. RESULTS: Double parathyroid
      adenomas are rare, occurring in 1.7 to 9% of patients with primary
      hyperparathyroidism. Most double parathyroid adenomas are synchronous lesions;
      few metachronous double parathyroid adenomas have previously been reported. Most
      parathyroid adenomas are of the chief cell variety, with oxyphil cell adenomas
      occurring in less than 1% of cases. In a 73-year-old man with no prior history or
      known family history of endocrine disease, primary hyperparathyroidism developed,
      and cervical ultrasonography demonstrated a mass in the right side of the neck.
      Subsequent parathyroidectomy revealed a right superior chief cell adenoma.
      Postoperatively, the patient's parathyroid hormone and serum calcium levels
      returned to normal and remained so for at least 9 years. Twelve years after the
      first operation, recurrent hyperparathyroidism prompted repeated surgical
      exploration of the neck, which disclosed a large left superior parathyroid mass.
      Surgical excision and histologic examination revealed the lesion to be an oxyphil
      cell adenoma. CONCLUSION: To our knowledge, this is the first reported case of
      metachronous double parathyroid adenomas involving two different cell types:
      chief cell and oxyphil cell.

PMID- 14715481
TI  - Cushing's syndrome caused by unsupervised use of ocular glucocorticoids.
AB  - OBJECTIVE: To report a case of Cushing's syndrome in an adult patient caused by
      prolonged and unsupervised use of glucocorticoid ocular drops. METHODS: We
      present the clinical and laboratory findings and describe the clinical course of
      our patient. RESULTS: A 33-year-old man with extensive ophthalmologic complaints
      and procedures, who had used glucocorticoid ocular drops for an extended period,
      was referred to the endocrinologist for new onset of type 2 diabetes mellitus.
      Clinically, the patient appeared cushingoid with a buffalo hump, thin skin,
      bruises, and purple striae, and his blood pressure was 130/90 mm Hg. Laboratory
      evaluation revealed a very low serum cortisol level with a concomitantly low
      normal level of adrenocorticotropic hormone (corticotropin). In addition, the
      response to a corticotropin stimulation test was abnormal, an indication of
      suppression of the adrenal glands. After the patient discontinued the use of the
      glucocorticoid eyedrops, his cushingoid features gradually faded, and his blood
      pressure and serum glucose levels normalized. CONCLUSION: Prolonged unsupervised
      use of glucocorticoid ocular drops may result in Cushing's syndrome and its
      numerous associated complications. Physicians and pharmacists should be aware of
      this possibility and must educate patients about the potentially serious adverse
      effects of such use.

PMID- 14715482
TI  - Nocturnal hypoglycemia: clinical manifestations and therapeutic strategies toward
      prevention.
AB  - OBJECTIVE: To review the features of nocturnal hypoglycemia and various
      preventive strategies. METHODS: We discuss the physiologic changes, the potential
      precipitating factors, the immediate and long-term effects, and the currently
      available options for treatment of nocturnal hypoglycemia in patients with
      diabetes. RESULTS: Nocturnal hypoglycemia is common in patients with type 1
      diabetes and is usually asymptomatic. Nocturnal hyperinsulinemia frequently
      occurs with insulin therapy, and although blood glucose levels are often low
      during sleep, they are seldom measured routinely. Almost 50% of all episodes of
      severe hypoglycemia occur at night during sleep. Such episodes can cause
      convulsions and coma and have been implicated as a precipitating factor in
      cardiac arrhythmias resulting in sudden death--the "dead-in-bed syndrome."
      Nocturnal hypoglycemia seems to have no immediate detrimental effect on cognitive
      function; however, on the following day, mood and well-being may be adversely
      affected. Recurrent exposure to nocturnal hypoglycemia may impair cognitive
      function; other substantial long-term morbidity includes the development of
      acquired hypoglycemia syndromes, such as impaired awareness of hypoglycemia,
      through the putative effect of unsuspected recurrent episodes of nocturnal
      hypoglycemia. CONCLUSION: In efforts to decrease the risk of nocturnal
      hypoglycemic episodes, various strategies can be used to minimize the nocturnal
      hyperinsulinemia that is associated with many insulin replacement regimens.
      Regular blood glucose monitoring (particularly at bedtime), the ingestion of
      appropriate bedtime snacks, and the utilization of short- and long-acting insulin
      analogues may all help to prevent or minimize the frequency of nocturnal
      hypoglycemia.

PMID- 14715483
TI  - American Association of Clinical Endocrinologists medical guidelines for clinical
      practice for the prevention and treatment of postmenopausal osteoporosis: 2001
      edition, with selected updates for 2003.

PMID- 14715485
TI  - Therapy for type 2 diabetes.

PMID- 14715486
TI  - Expression of adrenomedullin in hypoxic and ischemic rat kidneys and human
      kidneys with arterial stenosis.
AB  - To investigate regional aspects of hypoxic regulation of adrenomedullin (AM) in
      kidneys, we mapped the distribution of AM in the rat kidney after hypoxia
      (normobaric hypoxic hypoxia, carbon monoxide, and CoCl(2) for 6 h), anemia
      (hematocrit lowered by bleeding) and after global transient ischemia for 1 h
      (unilateral renal artery occlusion and reperfusion for 6 and 24 h) and segmental
      infarct (6 and 24 h). AM expression and localization was determined in normal
      human kidneys and in kidneys with arterial stenosis. Hypoxia stimulated AM mRNA
      expression significantly in rat inner medulla (CO 13 times, 8% O(2) 6 times, and
      CoCl(2) 8 times), followed by the outer medulla and cortex. AM mRNA level was
      significantly elevated in response to anemia and occlusion-reperfusion.
      Immunoreactive AM was associated with the thin limbs of Henle's loop, distal
      convoluted tubule, collecting ducts, papilla surface epithelium, and urothelium.
      AM labeling was prominent in the inner medulla after CO and in the outer medulla
      after occlusion-reperfusion. The infarct border zone was strongly labeled for AM.
      In cultured inner medullary collecting duct cells, AM mRNA was significantly
      increased by hypoxia. AM mRNA was equally distributed in human kidney and AM was
      localized as in the rat kidney. In human kidneys with artery stenosis, AM mRNA
      was not significantly enhanced compared with controls, but AM immunoreactivity
      was observed in tubules, vessels, and glomerular cells. In summary, AM expression
      was increased in the rat kidney in response to hypoxic and ischemic hypoxia in
      keeping with oxygen gradients. AM was widely distributed in the human kidney with
      arterial stenosis. AM may play a significant role to counteract hypoxia in the
      kidney.

PMID- 14715487
TI  - ANG II-induced downregulation of RBF after a prolonged reduction of renal
      perfusion pressure is due to pre- and postglomerular constriction.
AB  - Previous experiments from our laboratory showed that longer-lasting reductions in
      renal perfusion pressure (RPP) are associated with a gradual decrease in renal
      blood flow (RBF) that can be abolished by clamping plasma ANG II concentration
      ([ANG II]). The aim of the present study was to investigate the mechanisms behind
      the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30
      min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also
      measured glomerular filtration rate (GFR), proximal tubular pressure (P(prox)),
      and proximal tubular flow rate (Q(LP)). Early distal tubular fluid conductivity
      was measured as an estimate of early distal [NaCl] ([NaCl](ED)), and changes in
      plasma renin concentration (PRC) over time were measured. During 30 min of
      reduced RPP, RBF decreased gradually from 6.5 +/- 0.3 to 6.0 +/- 0.3 ml/min after
      5 min (NS) to 5.2 +/- 0.2 ml/min after 30 min (P < 0.05). This decrease occurred
      in parallel with a gradual increase in PRC from 38.2 +/- 11.0 x 10(-5) to 87.1 +/
      25.1 x 10(-5) Goldblatt units (GU)/ml after 5 min (P < 0.05) to 158.5 +/- 42.9 x
      10(-5) GU/ml after 30 min (P < 0.01). GFR, P(prox), and [NaCl](ED) all decreased
      significantly after 5 min and remained low. Estimates of pre- and postglomerular
      resistances showed that the autoregulatory mechanisms initially dilated
      preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced
      RPP, both pre- and postglomerular resistance had increased. We conclude that the
      decrease in RBF over time is caused by increases in both pre- and postglomerular
      resistance due to rising plasma renin and ANG II concentrations.

PMID- 14715488
TI  - Developmental regulation of prostaglandin E2 synthase in porcine ductus
      arteriosus.
AB  - The synthesis of PGE(2), the major vasodilator prostanoid of the ductus
      arteriosus (DA), is catalyzed by PGE(2) synthases (PGES). The factors implicated
      in increased PGE(2) synthesis in the perinatal DA are not known. We studied the
      developmental changes of PGES along with that of cyclooxygenase (COX)-2 and
      cytosolic phospholipase A(2) (cPLA(2)) in the DA of fetal (75-90% gestation) and
      immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES),
      COX-2, and PGE(2) in the DA of NB were approximately 7-fold higher than in fetus;
      activities of cytosolic PGES (cPGES) and cPLA(2) in DA of the fetus and NB did
      not differ. Because platelet-activating factor (PAF) could regulate COX-2
      expression, the former was measured and found to be more abundant in the DA of
      the NB than of fetus. PAF elicited an increase in mPGES, COX-2, and PGE(2) in
      fetal DA to levels approaching those of the NB; cPGES, cPLA(2), and COX-1 were
      unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315
      reduced mPGES, COX-2, and PGE(2) levels and were associated with increased DA
      tone. It is concluded that PAF contributes in regulating DA tone by governing
      mPGES, COX-2, and ensuing PGE(2) levels in the perinate.

PMID- 14715489
TI  - Cytochrome P-450 metabolites in endothelin-stimulated cardiac hormone secretion.
AB  - We examined the role of cytochrome P-450-arachidonate (CYP450-AA) metabolites in
      endothelin-1 (ET-1)-stimulated atrial natriuretic peptide (ANP) and pro-ANP-(1
      30) secretion from the heart. 17-Octadecynoic acid (17-ODYA, 10(-5) M)
      significantly inhibited ANP secretion stimulated by ET-1 (10(-8) M) in the
      isolated perfused rat atria and inhibited pro-ANP-(1-30) secretion stimulated by
      ET-1 (10(-8) M) or 20-hydroxyeicosatetraenoic acid in cultured neonatal rat
      ventricular myocytes (NRVM). In NRVM, 17-ODYA significantly (P < 0.05) increased
      secretion of cAMP but had no significant effect on the secretion of cGMP from
      NRVM. Staurosporine, an inhibitor of protein kinase C, completely blocked the
      inhibitory action of 17-ODYA, whereas a protein kinase A inhibitor, H-89 (5 x 10(
      5) M), did not significantly attenuate the effects of 17-ODYA. The results show
      that the inhibitory action of 17-ODYA on ET-1-augmented ANP secretion is mediated
      through cAMP and suggest that CYP450-AA may play an important role in ET-1
      induced cardiac hormone secretion.

PMID- 14715490
TI  - Effect of a perinatal high-salt diet on blood pressure control mechanisms in
      young Sprague-Dawley rats.
AB  - In the present investigation we sought to determine if a perinatal high-salt
      treatment affects blood pressure at an early age (30 days), and if so, to
      determine the mechanisms responsible for the hypertension. Pregnant dams were
      given an 8% NaCl diet [high-salt (HS) rats] during the final one-third of
      gestation and throughout the suckling period. After weaning, the pups continued
      to receive the high-salt diet until testing at age 30 days. Control groups
      received a normal-salt diet (NS rats). In HS rats, mean arterial pressure (MAP)
      was significantly increased (110 +/- 5 vs. 96 +/- 3 mmHg) compared with NS rats.
      Blockade of brain AT(1) receptors with intracerebroventricular losartan decreased
      MAP in HS but not NS rats. Blockade of alpha-adrenergic receptors with
      intravenous phentolamine or ganglionic transmission with intravenous
      chlorisondamine produced a greater decrease in MAP in HS rats. Baroreflex control
      of heart rate was assessed using a four-parameter logistics function. The mid
      range MAP (p3) was significantly increased in the HS rats. No other baroreflex
      parameters were affected. Specific binding of (125)I-[Sa (1),Ile(8)]ANG II to
      AT(1) receptors was increased in the subfornical organ (SFO) of the HS rats.
      Expression of AT(1a) receptor mRNA was greater in both SFO and PVN of the HS
      rats. These data suggest that even at an early age, Sprague-Dawley rats treated
      with a perinatal high-salt diet are hypertensive. The elevated blood pressure
      appears to be caused by increased sympathetic nervous activity, resulting, in
      part, from increased brain AT(1) receptor activation.

PMID- 14715491
TI  - Insulin-dependent diabetes impairs the inflammatory response and delays
      angiogenesis following Achilles tendon injury.
AB  - Although impaired wound healing associated with type 1 diabetes mellitus has been
      well studied in skin tissue, the influence of this metabolic disorder on tendon
      healing and recovery has not been extensively investigated. Because tendons are
      known to have limited repair potential, we studied the tendon-healing process by
      using a diabetic rat tendonitis model. We tested the hypothesis that diabetes
      influences the inflammatory response, cell proliferation, and angiogenesis in
      injured Achilles tendons. Diabetes was induced by injecting streptozotocin at 45
      mg/kg body wt. Non-diabetic rats as well as diabetic and insulin-treated diabetic
      animals were then injected with collagenase. The accumulation of inflammatory
      cells was quantified in transversal sections of Achilles tendon by using
      immunohistochemical staining at days 0, 1, 3, 7, 14, and 28 posttrauma. The
      number of proliferative cells and the extent of neovascularization was also
      quantified in the paratenon and the core of the tendon at days 0, 3, 7, 14, and
      28 posttrauma. Relative to nondiabetic and insulin-treated diabetic animals, the
      numbers of accumulated neutrophils and ED1(+) and ED2(+) macrophages in diabetic
      rats decreased by 46, 43, and 52%, respectively, in the first 3 days after injury
      compared with levels in nondiabetic and insulin-treated diabetic animals. The
      density of newly formed blood vessels decreased by 35 and 29% in the paratenon
      and the core of tendon, respectively, at days 3 and 7 after injury. Lastly, the
      concentration of proliferative cells decreased by 34% in the paratenon at day 7
      posttrauma in injured tendons from diabetic rats relative to nondiabetic rats.
      These results indicate that alterations in inflammatory, angiogenic, and
      proliferative processes occurred in the diabetic state that might eventually
      perturb tendon healing and remodeling.

PMID- 14715492
TI  - Human cerebrovascular and autonomic rhythms during vestibular activation.
AB  - Otolith activation increases muscle sympathetic nerve activity (MSNA), and MSNA
      activation may alter associations among autonomic oscillators, including those
      modulating cerebral hemodynamics. The purpose of this study was to determine the
      influence of vestibulosympathetic activation on cerebral and autonomic rhythms.
      We recorded the ECG, finger arterial pressure, end-tidal CO(2), respiration,
      cerebral blood flow velocity, and MSNA in eight subjects. Subjects breathed at
      0.25 Hz for 5 min in the prone and head-down positions. We analyzed data in time
      and frequency domains and performed cross-spectral analyses to determine
      coherence and transfer function magnitude. Head-down rotation increased MSNA from
      7 +/- 1.3 to 12 +/- 1.5 bursts/min (P = 0.001) but did not affect R-R intervals,
      arterial pressures, mean cerebral blood flow velocities (V(mean)), or their power
      spectra. Vestibular activation with head-down rotation had no effect on mean
      arterial pressure and V(mean) transfer function magnitude. The two new findings
      from this study are 1) head-down rotation independently activates the sympathetic
      nervous system with no effect on parasympathetic activity or V(mean); and 2)
      frequency-dependent associations between arterial pressures and V(mean) are
      independent of vestibular activation. These findings support the concept that
      vestibular-autonomic interactions independently and redundantly serve to maintain
      steady-state hemodynamics.

PMID- 14715493
TI  - A paracrine signaling role for serotonin in rat taste buds: expression and
      localization of serotonin receptor subtypes.
AB  - Recent advances in peripheral taste physiology now suggest that the classic
      linear view of information processing within the taste bud is inadequate and that
      paracrine processing, although undemonstrated, may be an essential feature of
      peripheral gustatory transduction. Taste receptor cells (TRCs) express multiple
      neurotransmitters of unknown function that could potentially participate in a
      paracrine role. Serotonin is expressed in a subset of TRCs with afferent
      synapses; additionally, TRCs respond physiologically to serotonin. This study
      explored the expression and cellular localization of serotonin receptor subtypes
      in TRCs as a possible route of paracrine communication. RT-PCR was performed on
      RNA extracted from rat posterior taste buds with 14 prime sets representing 5
      HT(1) through 5-HT(7) receptor subtype families. Data suggest that 5-HT(1A) and 5
      HT(3) receptors are expressed in taste buds. Immunocytochemistry with a 5-HT(1A)
      specific antibody demonstrated that subsets of TRCs were immunopositive for 5
      HT(1A). With the use of double-labeling, serotonin- and 5-HT(1A)-immunopositive
      cells were observed exclusively in nonoverlapping populations. On the other hand,
      5-HT(3)-immunopositive taste receptor cells were not observed. This observation,
      combined with other data, suggests 5-HT(3) is expressed in postsynaptic neural
      elements within the bud. We hypothesize that 5-HT release from TRCs activates
      postsynaptic 5-HT(3) receptors on afferent nerve fibers and, via a paracrine
      route, inhibits neighboring TRCs via 5-HT(1A) receptors. The ole of the 5-HT(1A)
      expressing TRC within the taste bud remains to be explored.

PMID- 14715494
TI  - Lethality during continuous anthrax lethal toxin infusion is associated with
      circulatory shock but not inflammatory cytokine or nitric oxide release in rats.
AB  - Although circulatory shock related to lethal toxin (LeTx) may play a primary role
      in lethality due to Bacillus anthracis infection, its mechanisms are unclear. We
      investigated whether LeTx-induced shock is associated with inflammatory cytokine
      and nitric oxide (NO) release. Sprague-Dawley rats with central venous and
      arterial catheters received 24-h infusions of LeTx (lethal factor 100 microg/kg;
      protective antigen 200 microg/kg) that produced death beginning at 9 h and a 7
      day mortality rate of 53%. By 9 h, mean arterial blood pressure, heart rate, pH,
      and base excess were decreased and lactate and hemoglobin levels were increased
      in LeTx nonsurvivors compared with LeTx survivors and controls (diluent only) (P
      < or = 0.05 for each comparing the 3 groups). Despite these changes, arterial
      oxygen and circulating leukocytes and platelets were not decreased and TNF-alpha,
      IL-beta, IL-6, and IL-10 levels were not increased comparing either LeTx
      nonsurvivors or survivors to controls. Nitrate/nitrite levels and tissue
      histology also did not differ comparing LeTx animals and controls. In additional
      experiments, although 24-h infusions of LeTx and Escherichia coli LPS produced
      similar mortality rates (54 and 56%, respectively) and times to death (13.2 +/-
      0.8 vs. 11.0 +/- 1.7 h, respectively) compared with controls, only LPS reduced
      circulating leukocytes, platelets, and IL-2 levels and increased TNF-alpha, IL-1
      alpha and -1 beta, IL-6, IL-10, interferon-gamma, granulocyte macrophage-colony
      stimulating factor, RANTES, migratory inhibitory protein-1 alpha, -2, and -3, and
      monocyte chemotactic protein-1, as well as nitrate/nitrite levels (all P < or =
      0.05 for the effects of LPS). Thus, in contrast to LPS, excessive inflammatory
      cytokine and NO release does not appear to contribute to the circulatory shock
      and lethality occurring with LeTx in this at model. Although therapies to
      modulate these host mediators may be applicable fo shock caused by LPS or other
      bacterial toxins, they may not with LeTx.

PMID- 14715495
TI  - Secretin depolarizes nucleus tractus solitarius neurons through activation of a
      nonselective cationic conductance.
AB  - The recent suggestion that secretin may be useful in treating autism and
      schizophrenia has begun to focus attention on the mechanisms underlying this gut
      brain peptide's actions in the central nervous system (CNS). In vitro
      autoradiographic localization of (125)I-secretin binding sites in rat brain shows
      the highest binding density in the nucleus tractus solitarius (NTS). Recent
      evidence suggests that intravenous infusion of secretin causes fos activation in
      NTS, a relay station playing important roles in the central regulation of
      autonomic functions. In this study, whole cell patch-clamp recordings were
      obtained from 127 NTS neurons in rat medullary slices. The mean resting membrane
      potential of these neurons was -54.7 +/- 0.3 mV, the mean input resistance was
      3.7 +/- 0.2 GOmega, and the action potential amplitude of these neurons was
      always >70 mV. Current-clamp studies showed that bath application of secretin
      depolarized the majority (80.8%; 42/52) of NTS neurons tested, whereas the
      remaining cells were either unaffected (17.3%; 9/52) or hyperpolarized (1.9%;
      1/52). These depolarizing effects were maintained in the presence of 5 microM TTX
      and found to be concentration dependent from 10(-12) to 10(-7) M. Using voltage
      clamp techniques, we also identified modulatory actions of secretin on specific
      ion channels. Our results demonstrate that while secretin is without effect on
      net whole cell potassium currents, it activates a nonselective cationic
      conductance (NSCC). These results show that NTS neurons are activated by secretin
      as a consequence of activation of a NSCC and support the emerging view that
      secretin can act as a neuropeptide within the CNS.

PMID- 14715496
TI  - Cardiovascular pathophysiology of environmental pollutants.

PMID- 14715497
TI  - Protein kinase betaII in Zucker obese rats compromises oxygen and flow-mediated
      regulation of nitric oxide formation.
AB  - In severe obesity, microvascular endothelial regulation of nitric oxide (NO)
      formation is compromised in response to muscarinic stimulation, and major
      arteries have suppressed flow-mediated dilation. Because normal microvessels are
      highly dependent on flow-mediated stimulation of NO generation and are responsive
      to intra- and extravascular oxygen availability, they are likely a major site of
      impaired endothelial regulation. This study evaluated the blood flow and oxygen
      dependent aspects of intestinal microvascular regulation and NO production in
      Zucker obese rats just before the onset of hyperglycemia. Ruboxistaurin (LY
      333531) was used to inhibit PKC-betaII to determine whether flow or oxygen
      related NO regulation was improved. Blood flow velocity was increased by forcing
      arterioles to perfuse approximately 50% larger tissue areas by occlusion of
      nearby arterioles, and oxygen tension in the bath was lowered to create a modest
      oxygen depletion. When compared with lean Zucker rats, the periarteriolar NO
      concentration ([NO]) for obese rats was approximately 30% below normal. At
      elevated shear rates, the [NO] for arterioles of obese animals was 20-30% below
      those in the arterioles of lean rats, and the NO response to decreased oxygen was
      about half normal in obese rats. All of these regulatory problems were
      essentially corrected in obese rats by PKC blockade with only minor changes in
      the microvascular behavior in lean rats. Therefore, activation of PKC-betaII in
      endothelial cells during obesity suppressed NO regulation both at rest and in
      response to increased flow velocity and decreased oxygen availability.

PMID- 14715498
TI  - Variable efficacy of N6-(1-iminoethyl)-L-lysine in acute cardiac transplant
      rejection.
AB  - We examined the efficacy and mechanism of action of N(6)-(1-iminoethyl)-L-lysine
      (L-NIL), a highly selective inhibitor of inducible nitric oxide (NO) synthase
      (iNOS), on acute cardiac transplant rejection. L-NIL produced a concentration
      dependent attenuation of plasma NO by-products and a decrease in nitrosylation of
      heme protein without altering protein levels of iNOS. At postoperative day 4, L
      NIL did not alter the increased binding activities for transcription factors
      nuclear factor-kappaB and activator protein-1. Whereas L-NIL decreased
      inflammatory cell infiltration, graft survival was only prolonged at the dose of
      1.0 microg/ml that incompletely blocked NO production. Higher L-NIL
      concentrations (30 and 60 microg/ml) ablated the increased NO production but
      failed to improve graft survival and even potentiated NF-kappaB binding activity
      examined at day 6. Alloimmune activation indicated by increased cytokine gene
      expression for interferon-gamma, interleukin-6, and interleukin-10 was inhibited
      in grafts only by treatment with 1.0 microg/ml L-NIL. These findings suggest a
      complex role of NO in acute cardiac allograft rejection. Partial inhibition of
      iNOS is beneficial to graft survival, whereas total ablation may oppose any
      benefits to graft survival. These studies have important implications in
      understanding the dual role of NO in acute rejection and help to reconcile
      discrepancies in the literature.

PMID- 14715499
TI  - Increased susceptibility to ventricular arrhythmias in a rodent model of
      experimental depression.
AB  - Depression is an important public health problem and is considered to be an
      independent risk factor for coronary artery disease. The pathophysiological
      mechanisms that link depression with adverse cardiovascular events (e.g.,
      myocardial ischemia, myocardial infarction, and sudden death) are not well
      established. It is possible that an increased susceptibility to life-threatening
      cardiac arrhythmias in depressed patients influences the risk of morbidity and
      mortality in coronary artery disease. This idea was tested with the use of an
      experimental model of depression that was developed to induce anhedonia, the
      reduced responsiveness to pleasurable stimuli observed in human depressed
      patients. Rats exposed to 4 wk of chronic mild stress (e.g., paired housing,
      strobe light, and white noise) displayed anhedonia, which was operationally
      defined by the reduced intake of a palatable sucrose solution relative to an
      established baseline and to control animals. Furthermore, compared with control
      rats, the anhedonic rats showed increased basal heart rate and decreased heart
      rate variability. In response to an intravenously infused chemical challenge,
      aconitine, anhedonic rats exhibited an increased vulnerability to ventricular
      arrhythmias, as indicated by a reduced threshold for premature ventricular
      complexes, salvos, and ventricular tachycardia. These findings suggest that the
      presence of depressive symptoms is associated with a lower threshold for
      ventricular arrhythmias, which may contribute to the increased risk for adverse
      cardiovascular events in patients with depression.

PMID- 14715500
TI  - Vasoactive effects of methylamine in isolated human blood vessels: role of
      semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide.
AB  - It is hypothesized that methylamine (MA) and semicarbazide-sensitive amine
      oxidase (SSAO) activity are involved in the cardiovascular complications in human
      diabetics. To test this, we 1) determined the acute vasoactive effects of MA (1
      1,000 micromol/l) in uncontracted and norepinephrine (NE; 1 micromol/l)
      precontracted human blood vessels used for coronary artery bypass grafts [left
      internal mammary artery (LIMA), radial artery (RA), and right saphenous vein
      (RSV)]; 2) tested whether MA effects in LIMA and RSV were dependent on SSAO
      activity using the SSAO inhibitor semicarbazide (1 mmol/l, 15 min); 3) determined
      the effects of MA metabolites formaldehyde and hydrogen peroxide in LIMA and RSV;
      4) tested whether the MA response was nitric oxide, prostaglandin, or
      hyperpolarization dependent; 5) measured the LIMA and RSV cGMP levels after MA
      exposure; and 6) quantified SSAO activity in LIMA, RA, and RSV. In NE
      precontracted vessels, MA stimulated a biphasic response in RA and RSV (rapid
      contraction followed by prolonged relaxation) and dominant relaxation in LIMA
      (mean +/- SE, %relaxation: 55.4 +/- 3.9, n = 30). The MA-induced relaxation in
      LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly
      blocked MA-induced relaxation (%inhibition: 82.5 +/- 4.8, n = 7) and SSAO
      activity (%inhibition: 98.1 +/- 1.3, n = 26) in LIMA. Formaldehyde (%relaxation:
      37.3 +/- 18.6, n = 3) and H(2)O(2) (%relaxation: 55.6 +/- 9.0, n = 9) at 1 mmol/l
      relaxed NE-precontracted LIMA comparable with MA. MA-induced relaxation in LIMA
      was nitric oxide, prostaglandin, and possibly cGMP independent and blocked by
      hyperpolarization. We conclude that vascular SSAO activity may convert endogenous
      amines, like MA, to vasoactive metabolites.

PMID- 14715501
TI  - Modulation of arterial baroreflex control of muscle sympathetic nerve activity by
      muscle metaboreflex in humans.
AB  - We aimed to investigate the interaction [with respect to the regulation of muscle
      sympathetic nerve activity (MSNA) and blood pressure] between the arterial
      baroreflex and muscle metaboreflex in humans. In 10 healthy subjects who
      performed a 1-min sustained handgrip exercise at 50% maximal voluntary
      contraction followed by forearm occlusion, arterial baroreflex control of MSNA
      (burst incidence and strength and total activity) was evaluated by analyzing the
      relationship between beat-by-beat spontaneous variations in diastolic arterial
      blood pressure (DAP) and MSNA both during supine rest (control) and during
      postexercise muscle ischemia (PEMI). During PEMI (vs. control), 1) the linear
      relationship between burst incidence and DAP was shifted rightward with no
      alteration in sensitivity, 2) the linear relationship between burst strength and
      DAP was shifted rightward and upward with no change in sensitivity, and 3) the
      linear relationship between total activity and DAP was shifted to a higher blood
      pressure and its sensitivity was increased. The modification of the control of
      total activity that occurs in PEMI could be a consequence of alterations in the
      baroreflex control of both MSNA burst incidence and burst strength. These results
      suggest that the arterial baroreflex and muscle metaboreflex interact to control
      both the occurrence and strength of MSNA bursts.

PMID- 14715502
TI  - Mechanical, cellular, and molecular factors interact to modulate circulating
      endothelial cell progenitors.
AB  - It appears that there are two classes of human circulating endothelial cell (EC)
      progenitors, CD34+ and CD34-CD14+ cells. Attention has focused on CD34+ cells,
      yet CD34-CD14+ monocytic cells are far more abundant and may represent the most
      common class of circulating EC progenitor. Little is known about molecular or
      physiological factors that regulate putative CD34-CD14+ EC progenitor function,
      although factors secreted by other blood and cardiovascular cells to which they
      are exposed probably affect their behavior. Hypoxia and stretch are two important
      physiological stimuli known to trigger growth factors in cardiovascular cells and
      accordingly may modulate EC progenitors. To investigate the impact of these
      environmental parameters on EC progenitors, EC production in CD34-CD14+ cultures
      was evaluated. Our data indicate that neither stretch nor hypoxia alters EC
      production by EC progenitors directly but do so indirectly through their effects
      on cardiovascular cells. Conditioned media (CM) from coronary artery smooth
      muscle cells inhibit EC production in culture, and this inhibition is stronger if
      the coronary smooth muscle cells have been subjected to cyclic stretch. In
      contrast, cardiomyocyte CM increases EC cell number, an effect that is
      potentiated if the myocytes have been subjected to hypoxia. Significantly, EC
      progenitor responses to CM are altered by the presence of CD34-CD14- peripheral
      blood mononuclear cells (PBMCs). Moreover, CD34-CD14- PBMCs attenuate EC
      progenitor responsiveness to the angiogenic factors basic fibroblast growth
      factor (FGF-2), vascular endothelial cell growth factor-A165, and erythropoietin
      while inducing EC progenitor death in the presence of transforming growth factor
      beta1 in vitro

PMID- 14715503
TI  - Extracellular ATP facilitates flow-induced vasodilatation in rat small mesenteric
      arteries.
AB  - ATP can be released from endothelial cells, and this release is increased by
      intraluminal flow in blood vessels. In the present study, the effect of
      extracellular ATP (1 microM) on flow-induced vasodilatation was investigated in
      isolated and pressurized rat small mesenteric arteries. In the absence of
      extracellular ATP, only 46% of arteries developed dilatation in response to flow,
      and this response was both transient and unstable. In marked contrast, with ATP
      present, all vessels developed a prolonged and stable dilatation in response to
      flow. Even in the vessels that failed to respond to flow in the absence of ATP,
      dilatation could be stimulated once ATP was present. The ability of ATP to
      facilitate flow-induced vasodilatation was mimicked by UTP (1 microM), a P2Y
      agonist, or 3'-O-(4-benzoyl)benzoyl ATP (BzATP; 10 microM), an agonist for P2X1,
      P2X7, and P2Y11 purinoceptors. The involvement of P2X7 purinoceptors was further
      supported by the inhibitory effect of KN-62 (1 microM), a P2X7 antagonist, on the
      action of BzATP. P2X1 and P2X3 purinoceptors were not involved because their
      receptor agonist alpha,beta-methylene ATP had no effect. The facilitating effect
      of ATP on flow dilatation was also attenuated by the combined application of
      reactive blue 2 (100 microM), a P2Y antagonist, and suramin (100 microM), a
      nonselective P2X and P2Y antagonist. Furthermore, flow-induced dilatation
      obtained in the presence of ATP was reproducible. In contrast, in the additional
      presence of the ectonucleotidase inhibitor ARL-67156 (10 microM), although the
      first dilatation was normal, the responses to the second and later exposures to
      flow were greatly attenuated. The nonhydrolyzable ATP analogs adenosine-5'-(3
      thiotriphosphate)trilithium salt (1 microM) and adenosine 5'-(beta,gamma-imido)
      triphosphate tetralithium salt hydrate (10 microM) had similar effects to those
      of ARL-67156. These data suggest that ATP acts through both P2X and P2Y
      purinoceptors to facilitate flow-induced vasodilatation and that
      ectonucleotidases prevent this effect by degrading ATP on the endothelial cell
      surface.

PMID- 14715504
TI  - Electrotonic load triggers remodeling of repolarizing current Ito in ventricle.
AB  - A change in activation sequence electrically remodels ventricular myocardium,
      causing persistent changes in repolarizing currents (T-wave memory). However, the
      underlying mechanism for triggering activation sequence-dependent remodeling is
      unknown. Optical action potentials were mapped with high resolution from the
      epicardial surface of the arterially perfused canine wedge preparation (n = 23)
      during 30 min of baseline endocardial stimulation, followed by 40 min of
      epicardial stimulation, and, finally, restoration of endocardial stimulation.
      Immediately after the change from endocardial to epicardial stimulation, phase 1
      notch amplitude of epicardial cells was attenuated by 74 +/- 8% (P < 0.001)
      compared with baseline and continued to diminish during the period of epicardial
      pacing, suggesting progressive remodeling of the transient outward current (Ito).
      When endocardial pacing was restored, notch amplitude did not immediately recover
      but remained attenuated by 23 +/- 10% (P < 0.001), also consistent with a
      remodeling effect. Peak Ito current measured from isolated epicardial myocytes
      changed by 12 +/- 4% (P < 0.025), providing direct evidence for Ito remodeling
      occurring on a surprisingly short time scale. The mechanism for triggering
      remodeling of Ito was a significant reduction (by 14 +/- 4%, P < 0.001) of
      upstroke amplitude in epicardial cells during epicardial stimulation. Reduction
      in upstroke amplitude during epicardial pacing was explained by electrotonic load
      on epicardial cells by fully repolarized downstream endocardial cells. These data
      suggest a novel mechanism for triggering electrical remodeling in the ventricle.
      Electrotonic load imposed by a change in activation sequence reduces upstroke
      amplitude, which, in turn, attenuates Ito according to its known voltage
      dependent properties, triggering downregulation of current.

PMID- 14715505
TI  - Expressions of adrenomedullin mRNA and protein in rats with hypobaric hypoxia
      induced pulmonary hypertension.
AB  - Experimental pulmonary hypertension induced in a hypobaric hypoxic environment
      (HHE) is characterized by structural remodeling of the heart and pulmonary
      arteries. Adrenomedullin (AM) has diuretic, natriuretic, and hypotensive effects.
      To study the possible effects of HHE on the AM synthesis system, 150 male Wistar
      rats were housed in a chamber at the equivalent of a 5,500-m altitude level for
      21 days. After 14 days of exposure to HHE, pulmonary arterial pressure (PAP) was
      significantly increased (compared with control rats). The plasma AM protein level
      was significantly increased on day 21 of exposure to HHE. In the right ventricle
      (RV), right atrium, and left atrium of the heart, the expressions of AM mRNA and
      protein were increased in the middle to late phase (5-21 days) of HHE, whereas in
      the brain and lung they were increased much earlier (0.5-5 days). In situ
      hybridization and immunohistochemistry showed AM mRNA and protein staining to be
      more intense in the RV in animals in the middle to late phase of HHE exposure
      than in the controls. During HHE, these changes in AM synthesis, which occurred
      strongly in the RV, occurred alongside the increase in PAP. Conceivably, AM may
      play a role in modulating pulmonary hypertension in HHE.

PMID- 14715506
TI  - Spatial comparison between wall shear stress measures and porcine arterial
      endothelial permeability.
AB  - A better understanding of how hemodynamic factors affect the integrity and
      function of the vascular endothelium is necessary to appreciate more fully how
      atherosclerosis is initiated and promoted. A novel technique is presented to
      assess the relation between fluid dynamic variables and the permeability of the
      endothelium to macromolecules. Fully anesthetized, domestic swine were
      intravenously injected with the albumin marker Evans blue dye, which was allowed
      to circulate for 90 min. After the animals were euthanized, silicone casts were
      made of the abdominal aorta and its iliac branches. Pulsatile flow calculations
      were subsequently made in computational regions derived from the casts. The
      distribution of the calculated time-dependent wall shear stress in the external
      iliac branches was directly compared on a point-by-point basis with the spatially
      varying in vivo uptake of Evans blue dye in the same arteries. The results
      indicate that in vivo endothelial permeability to albumin decreases with
      increasing time-average shear stress over the normal range. Additionally,
      endothelial permeability increases slightly with oscillatory shear index.

PMID- 14715507
TI  - Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat
      heart.
AB  - Fetal programming has profound effects on cardiovascular function in later adult
      life. We tested the hypothesis that chronic hypoxic exposure during fetal
      development downregulates endogenous cardioprotective mechanisms in adult rats.
      Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 from
      days 15 to 21 of gestation) groups. The male progeny were studied at 2 mo of age.
      Rats were subjected to heat stress (42 degrees C for 15 min). After 24 h, hearts
      were excised and subjected to 30 min of global ischemia and 1 h of reperfusion.
      Prenatal hypoxia did not change adult rat body weight and heart weight, but
      significantly increased the cross-sectional area of a left ventricular (LV)
      myocyte. Heat stress significantly improved postischemic recovery of LV function
      in normoxic control rats, but not in prenatally hypoxic rats. The infarct size in
      the LV resulting from ischemia-reperfusion was reduced by the heat stress
      pretreatment in control rats, but not in prenatally hypoxic rats. In accordance,
      heat stress significantly increased LV myocardial content of heat shock protein
      70 only in normoxic control rats. In addition, there was a significant decrease
      in the LV myocardial content of the PKC-epsilon isoform in prenatally hypoxic
      rats compared with control rats. We conclude that prenatal hypoxia causes in
      utero programming of hsp70 gene in the LV, leading to an inhibition of its
      response to heat stress and a loss of cardioprotection in later adult life.

PMID- 14715508
TI  - Demonstration of altered signaling responses in bone marrow extracellular fluid
      during increased hematopoiesis in rats using a centrifugation method.
AB  - The composition and characteristics of the bone marrow extracellular fluid
      supposedly modify the transport of cytokines, drugs, and other signaling
      molecules involved in the regulation of bone marrow function. Direct access to
      the bone marrow extracellular fluid surrounding hematopoietic cells is
      complicated by the virtually noncompliant surrounding bone tissue. We examined
      the applicability of a centrifugation method to obtain representative samples of
      bone marrow extracellular fluid from rats and humans. Perforated rat bones or
      human bone marrow biopsies were wrapped in nylon mesh baskets before being
      centrifuged at 180-239 g. In the rats, we found an only minor contribution of
      fluid from other sources than the bone marrow extracellular fluid as indicated by
      the average ratio of centrifugate-to-plasma activity of the extracellular tracer
      fluid 51Cr-labeled EDTA of 0.85. The colloid osmotic pressure in the centrifugate
      was consistently lower than that in the corresponding plasma in both species. In
      rats and humans, high-performance liquid chromatography showed a protein elution
      pattern from the bone marrow fluid similar to that of plasma, except for a peak
      eluting in the approximately 40-kDa molecular mass range. Western blotting of the
      cytokines erythropoietin and granulocyte colony-stimulating factor revealed
      generally higher amounts in the centrifugate than in the plasma. This difference
      was augmented during increased hematopoietic activity induced by inflammation or
      bleeding in rats. We conclude that the centrifugation method provides
      representative samples of bone marrow extracellular fluid and that extracellular
      signaling responses to altered hematopoiesis are more clearly reflected locally
      in the bone marrow interstitium than in plasma.

PMID- 14715509
TI  - Differential contribution of necrosis and apoptosis in myocardial ischemia
      reperfusion injury.
AB  - Necrosis and apoptosis differentially contribute to myocardial injury.
      Determination of the contribution of these processes in ischemia-reperfusion
      injury would allow for the preservation of myocardial tissue. Necrosis and
      apoptosis were investigated in Langendorff-perfused rabbit hearts (n = 47)
      subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25
      (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion.
      Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining,
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),
      bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9
      cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD).
      The contribution of apoptosis was determined separately (n = 42) using
      irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed
      pressure (LVPDP) and systolic shortening (SS) were significantly decreased and
      infarct size and TUNEL-positive cells were significantly increased (P < 0.05 vs.
      Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and
      caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD,
      and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of
      caspase-3 and -9 activity significantly decreased (P < 0.05) infarct size at GI
      25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a
      significant increase in both necrosis and apoptosis (P < 0.05 vs. Control group)
      evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic
      proapoptotic activation is evident early during ischemia but does not
      significantly contribute to infarct size before GI-25. The contribution of
      necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than
      that of apoptosis. Apoptosis is significantly decreased by caspase inhibition
      during early reperfusion, but this protection does not improve immediate
      postischemic functional recovery.

PMID- 14715510
TI  - Leukocyte dependence of platelet adhesion in postcapillary venules.
AB  - Reperfusion of ischemic tissues results in development of a proinflammatory,
      prothrombogenic phenotype, culminating in the recruitment of leukocytes and
      platelets within postcapillary venules. Recent studies have indicated an
      interdependence of platelet and leukocyte adhesion, suggesting that heterotypic
      blood cell interactions may account for postischemic platelet recruitment. The
      objectives of this study were to 1) determine whether ischemia-reperfusion (I/R)
      induced platelet recruitment is leukocyte dependent and 2) quantify the
      contributions of leukocytes and endothelial cells in this platelet recruitment.
      Intravital microscopy was used to monitor the recruitment of fluorescently
      labeled platelets in postcapillary venules of the small intestine after 45-min
      ischemia and 4-h reperfusion. To assess the leukocyte dependence of platelet
      adhesion, platelets from wild-type mice were infused into mice deficient in
      neutrophils and/or lymphocytes and mice deficient in key leukocyte adhesion
      molecules (CD18 and ICAM-1). These antileukocyte strategies resulted in
      significantly reduced platelet recruitment. Simultaneous visualization of
      platelets and leukocytes enabled quantification of leukocyte-dependent and
      endothelium-dependent platelet adhesion. It was observed that in wild-type
      animals 74% of I/R-induced platelet adhesion was a result of platelet-leukocyte
      interactions. Although the majority of adherent platelets were associated with
      leukocytes, <50% of adherent leukocytes were platelet bearing, suggesting that
      not all adherent leukocytes support platelet adhesion. These results are
      consistent with leukocytes playing a major role in supporting I/R-induced
      platelet adhesion.

PMID- 14715511
TI  - Excitatory amino acids in rostral ventrolateral medulla support blood pressure
      during water deprivation in rats.
AB  - Water deprivation is associated with regional increases in sympathetic tone, but
      whether this is mediated by changes in brain stem regulation of sympathetic
      activity is unknown. Therefore, this study tested the hypothesis that water
      deprivation increases excitatory amino acid (EAA) drive of the rostral
      ventrolateral medulla (RVLM), by determining whether bilateral microinjection of
      kynurenate (Kyn; 2.7 nmol) into the RVLM decreases arterial pressure more in
      water-deprived than water-replete rats. Plasma osmolality was increased in 48-h
      water-deprived rats (313 +/- 1 mosmol/kgH2O; P < 0.05) compared with 24-h water
      deprived rats (306 +/- 2 mosmol/kgH2O) and water-replete animals (300 +/- 2
      mosmol/kgH2O). Kyn decreased arterial pressure by 28.1 +/- 5.2 mmHg (P < 0.01) in
      48-h water-deprived rats but had no effect in water-replete rats (-5.9 +/- 1.3
      mmHg). Variable depressor effects were observed in 24-h water-deprived animals (
      12.5 +/- 2.4 mmHg, not significant); however, in all rats the Kyn depressor
      response was strongly correlated to the osmolality level (P < 0.01; r2 = 0.47).
      The pressor responses to unilateral microinjection of increasing doses (0.1, 0.5,
      1.0, and 5.0 nmol) of glutamate were enhanced (P < 0.05) during water
      deprivation, but the pressor responses to intravenous phenylephrine injection
      were smaller (P < 0.05). These data suggest that water deprivation increases EAA
      drive to the RVLM, in part by increasing responsiveness of the RVLM to EAA such
      as glutamate.

PMID- 14715512
TI  - Developmental differences in L-type calcium current of human atrial myocytes.
AB  - We investigated differences in L-type Ca2+ current (ICa) between infant (INF, 1
      12 mo old), young adult (YAD, 14-18 yr old), and older adult (AD) myocytes from
      biopsies of right atrial appendages. Basal ICa was smaller in INF myocytes (1.2
      +/- 0.1 pA/pF, n = 29, 6 +/- 1 mo old, 11 patients) than in YAD (2.5 +/- 0.2
      pA/pF, n = 20, 16 +/- 1 yr old, 5 patients) or AD (2.6 +/- 0.3 pA/pF, n = 19, 66
      +/- 3 yr old, 9 patients) myocytes (P < 0.05). Maximal ICa produced by
      isoproterenol (Iso) was similar in INF, YAD, and AD cells: 8.4 +/- 1.1, 9.6 +/-
      1.0, and 9.2 +/- 1.3 pA/pF, respectively. Efficacy (Emax) was larger in INF (607
      +/- 50%) than for YAD (371 +/- 29%) or AD (455 +/- 12%) myocytes. Potency (EC50)
      was 8- to 10-fold higher in AD (0.82 +/- 0.09 nM) or YAD (0.41 +/- 0.14 nM) than
      in INF (7.6 +/- 3.5 nM) myocytes. Protein levels were similar for Gialpha2 but
      much greater for Gialpha3 in INF than in AD or YAD atrial tissue. When Gialpha3
      activity was inhibited by inclusion of a Gialpha3 COOH-terminal decapeptide in
      the pipette, basal ICa and the response to 10 nM Iso were increased in INF, but
      not in YAD, cells. We propose that basal ICa and the response to low-dose beta
      adrenergic stimulation are inhibited in INF (but not YAD or AD) cells as a result
      of constitutive inhibitory effects of Gialpha3.

PMID- 14715513
TI  - Myocardial ischemia-reperfusion injury is enhanced in a model of systemic allergy
      and asthma.
AB  - Despite epidemiological evidence of cardiovascular complications in asthmatics,
      the direct contribution of asthmatic pathophysiology to cardiovascular effects is
      unknown. Considering parallels in underlying pathophysiology, we tested the
      hypothesis that presence of systemic allergy and asthma worsens the outcome of
      myocardial ischemia-reperfusion injury. Systemic allergy and asthma were created
      in rabbits by repeated intraperitoneal injections of allergen with adjuvant,
      followed by an airway challenge in two groups. Nonsensitized animals served as
      controls. In situ myocardial ischemia-reperfusion was induced in anesthetized
      animals by a 30-min ligation of a coronary artery, followed by 3 h of
      reperfusion. Ischemia-reperfusion was done at 24 h after intraperitoneal boost (1
      DB) and 7 days (7 DB) after the last intraperitoneal injection and at 24 h
      (1DAWCH) and 7 days (7DAWCH) after airway challenge. The infarct size (determined
      by 2,3,5-triphenyltetrazolium chloride staining, normalized to area at risk) was
      significantly higher in all sensitized groups compared with control (1DB, 31 +/-
      4; 7DB, 28.9 +/- 2.6; 1DAWCH, 66.1 +/- 4.1; 7DAWCH, 28.9 +/- 9.2; control, 16.7
      +/- 3.2; means +/- SE; P < 0.01 by ANOVA; n = 6). The 1DAWCH group showed
      significantly greater infarct than all other groups (P < 0.05). Myocardial
      neutrophil infiltration was significantly higher in the sensitized groups
      compared with control (P < 0.01). Tissue neutrophil counts showed a strong
      positive correlation to infarct sizes (r2 = 0.9). These observations indicate
      that the presence of systemic allergy and asthma is associated with increased
      myocardial neutrophil infiltration during acute ischemia-reperfusion and
      increased size of the resulting infarct.

PMID- 14715514
TI  - Regulation of rat pial arteriolar smooth muscle relaxation in vivo through
      multidrug resistance protein 5-mediated cGMP efflux.
AB  - Multidrug resistance protein 5 (MRP5) has been linked to cGMP cellular export in
      peripheral vascular smooth muscle cells (VSMCs) and is widely expressed in brain
      vascular tissue. In the present study, we examined whether knockdown of MRP5 in
      pial arterioles [via antisense oligodeoxynucleotide (ODN) applications] affected
      nitric oxide (NO)/cGMP-induced dilations. The antisense or (as a control)
      missense ODN was applied to the cortical surface approximately 24 h before study
      via closed cranial windows. The efficacy of the antisense vs. missense ODN in
      eliciting selective reductions in MRP5 expression was confirmed by analysis of
      MRP5 mRNA in pial tissue. Unexpectedly, in initial studies, a significantly lower
      maximal pial arteriolar diameter increase in the presence of the NO donor S
      nitrosoacetylpenicillamine (SNAP) was seen in the antisense vs. missense ODN
      treated rats (35 vs. 48% diameter increase, respectively). It was suspected that
      this related to a reduced vascular smooth muscle cell sensitivity to cGMP due to
      prolonged exposure to increased intracellular cGMP levels elevated by overnight
      restriction of cGMP efflux. That postulate was supported by a finding of a
      diminished vasodilating response to the cGMP-dependent protein kinase-activating
      cGMP analog 8-p-chlorophenylthio-cGMP in antisense vs. missense ODN-treated rats.
      To prevent desensitization, additional rats were studied in the presence of
      chronic NOS inhibition via Nomega-nitro-L-arginine. In the NO synthase (NOS)
      inhibited rats, the maximal SNAP response was much higher in the antisense (62%
      increase) vs. the missense ODN (40% increase) group. A similar result was
      obtained when monitoring responses to the soluble guanylyl cyclase-activating
      drugs YC-1 and BAY 41-2272. Moreover, in the presence of NOS inhibition, the
      normal SNAP-induced rise in periarachnoid cerebrospinal fluid cGMP levels, which
      reflects cGMP efflux, was absent in the antisense ODN-treated rats, a finding
      consistent with loss of MRP5 function. In conclusion, if one minimizes the
      confounding effects of basal cGMP production, a clearer picture emerges, one that
      indicates an important role for MRP5-mediated cGMP efflux in the regulation of NO
      induced cerebral arteriolar relaxation.

PMID- 14715515
TI  - Gastrointestinal satiety signals II. Cholecystokinin.
AB  - During a meal, ingested nutrients accumulate in the stomach, with a significant
      portion passing on to the small intestine. The gastrointestinal presence of
      ingested nutrients initiates a range of physiological responses that serve to
      facilitate the overall digestive process. Thus peptides and transmitters are
      released, and various neural elements are activated that coordinate
      gastrointestinal secretion and motility and can eventually lead to meal
      termination or satiety. Among the range of gastrointestinal peptides released by
      ingested nutrients is the brain/gut peptide CCK. CCK plays a variety of roles in
      coordinating gastrointestinal activity and has been demonstrated to be an
      important mediator for the control of meal size.

PMID- 14715516
TI  - Apoptosis versus necrosis in acute pancreatitis.
AB  - Acute pancreatitis is a disease of variable severity in which some patients
      experience mild, self-limited attacks, whereas others manifest a severe, highly
      morbid, and frequently lethal attack. The events that regulate the severity of
      acute pancreatitis are, for the most part, unknown. It is generally believed that
      the earliest events in acute pancreatitis occur within acinar cells and result in
      acinar cell injury. Other processes, such as recruitment of inflammatory cells
      and generation of inflammatory mediators, are believed to occur subsequent to
      acinar cell injury, and these "downstream" events are believed to influence the
      severity of the disease. Several recently reported studies, however, have
      suggested that the acinar cell response to injury may, itself, be an important
      determinant of disease severity. In these studies, mild acute pancreatitis was
      found to be associated with extensive apoptotic acinar cell death, whereas severe
      acute pancreatitis was found to involve extensive acinar cell necrosis but very
      little acinar cell apoptosis. These observations led to the hypothesis that
      apoptosis could be a favorable response to acinar cells and that interventions
      that favor induction of apoptotic, as opposed to necrotic, acinar cell death
      might reduce the severity of an attack of acute pancreatitis. Indeed, in an
      experimental setting, the induction of pancreatic acinar cell apoptosis protects
      mice against acute pancreatitis. Little is known about the mechanism of apoptosis
      in the pancreatic acinar cell, although some early attempts have been made in
      that direction. Also, clinical relevance of these experimental studies remains to
      be investigated.

PMID- 14715517
TI  - Induced nitric oxide promotes intestinal inflammation following hemorrhagic
      shock.
AB  - In hemorrhagic shock (HS), increased cytokine production contributes to tissue
      inflammation and injury through the recruitment of neutrophils [polymorphonuclear
      cells (PMN)]. HS stimulates the early expression of inducible nitric oxide
      synthase (iNOS) that modulates proinflammatory activation after hemorrhage.
      Experiments were performed to determine the contribution of iNOS to gut
      inflammation and dysmotility after HS. Rats subjected to HS (mean arterial
      pressure 40 mmHg for 2.5 h followed by resuscitation and death at 4 h)
      demonstrated histological signs of mucosal injury, impairment of intestinal
      smooth muscle contractility, extravasation of PMN, and increased gut mRNA levels
      of ICAM-1, IL-6, and granulocyte colony-stimulating factor (G-CSF). In addition,
      DNA binding activity of NF-kappaB and Stat3, an IL-6 signaling intermediate, was
      significantly increased. In shocked rats treated with the selective iNOS
      inhibitor l-N(6)-(1-iminoethyl)lysine at the time of resuscitation, histological
      signs of intestinal injury and PMN infiltration were reduced and muscle
      contractility was almost completely restored. Selective iNOS inhibition in
      shocked animals reduced the binding activity of NF-kappaB and Stat3 and reduced
      mRNA levels of ICAM-1, IL-6, and G-CSF. The results of studies using iNOS
      knockout mice subjected to HS were similar. We propose that early upregulation of
      iNOS contributes to the inflammatory response in the gut wall and participates in
      the activation of signaling cascades and cytokine expression that regulate
      intestinal injury, PMN recruitment, and impaired gut motility.

PMID- 14715518
TI  - Activation of intestinal smooth muscle cells by interstitial cells of Cajal in
      simulation studies.
AB  - Activation of a two-dimensional sheet network (5 parallel chains of 5 cells each)
      of simulated intestinal smooth muscle cells (SMCs) by one interstitial cell of
      Cajal (ICC) was modeled by PSpice simulation. The network of 25 cells was not
      interconnected by gap-junction channels; instead, excitation was transmitted by
      the electric field that develops in the junctional clefts (JC) when the
      prejunctional membrane fires an action potential (AP). Transverse propagation
      between the parallel chains occurs similarly. The ICC cell was connected to cell
      E5 of the network [5th cell of the 5th (E) chain] via a high-resistance junction.
      The stimulating current, applied to the ICC cell interior, was made to resemble
      the endogenous undershooting slow wave (I(SW)). An I(SW) of 2.4 nA (over a rise
      time of 4 ms) took the ICC cell from a resting potential (RP) of -80 mV to a
      membrane potential of -41 mV. The slow wave produced a large negative cleft
      potential in the JC (V(JC); ICC-E5). The V(jc) brought the postjunctional
      membrane of E5 to threshold, causing this cell to fire an AP. This, in turn,
      propagated throughout the SMC network. If the ICC cell was given an RP of -55 mV
      (like SMC) and a slow wave of 40 mV amplitude (I(SW) of 1.8 nA), it still
      activated the SMC network. This was also true when the ICC cell was made
      excitable (developing an overshooting, fast-rising AP). In summary, one ICC cell
      displaying a slow wave was capable of activating a network of SMC in the absence
      of gap junctions.

PMID- 14715519
TI  - Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic
      inflammation.
AB  - Colitis in interleukin-2-deficient (IL-2(-/-)) mice resembles ulcerative colitis
      in humans. We studied epithelial transport and barrier function in IL-2(-/-) mice
      and used this model to characterize mechanisms of diarrhea during intestinal
      inflammation. (22)Na(+) and (36)Cl(-) fluxes were measured in proximal colon. Net
      Na(+) flux was reduced from 4.0 +/- 0.5 to 0.8 +/- 0.5 micromol.h(-1).cm(-2),
      which was paralleled by diminished mRNA and protein expression of the Na(+)/H(+)
      exchanger NHE3. Net Cl(-) flux was also decreased from 2.2 +/- 1.6 to -2.7 +/-
      0.6 micromol.h(-1).cm(-2), indicating impaired Na(+)-Cl(-) absorption. In distal
      colon, aldosterone-induced electrogenic Na(+) absorption was 6.1 +/- 0.9
      micromol.h(-1).cm(-2) in controls and was abolished in IL-2(-/-) mice.
      Concomitantly, mRNA expression of beta- and gamma-subunits of the epithelial
      sodium channel (ENaC) was reduced. Epithelial barrier was studied in proximal
      colon by impedance technique and mannitol fluxes. In contrast to ulcerative
      colitis, epithelial resistance was increased and mannitol fluxes were decreased
      in IL-2(-/-) mice. This was in accord with the findings of reduced ion transport
      as well as increased expression of tight junction proteins occludin and claudin
      1, -2, -3, and -5. In conclusion, the IL-2(-/-) mucosa exhibits impaired
      electroneutral Na(+)-Cl(-) absorption and electrogenic Na(+) transport due to
      reduced mRNA and protein expression of NHE3 and ENaC beta- and gamma-subunit
      mRNA. This represents a model of early intestinal inflammation with absorptive
      dysfunction due to impaired transport protein expression/function while
      epithelial barrier is still intact. Therefore, this model is ideal to study
      regulation of transporter expression independent of barrier defects.

PMID- 14715520
TI  - Protection from ischemic liver injury by activation of A2A adenosine receptors
      during reperfusion: inhibition of chemokine induction.
AB  - Ischemia-reperfusion (I/R) injury occurs as a result of restoring blood flow to
      previously hypoperfused vessels or after tissue transplantation and is
      characterized by inflammation and microvascular occlusion. We report here that 4
      [3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2
      yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester (ATL146e), a selective
      agonist of the A(2A) adenosine receptor (A(2A)AR), profoundly protects mouse
      liver from I/R injury when administered at the time of reperfusion, and
      protection is blocked by the antagonist ZM241385. ATL146e lowers liver damage by
      90% as assessed by serum glutamyl pyruvic transaminase and reduces hepatic edema
      and MPO. Most protection remains if ATL146e treatment is delayed for 1 h but
      disappears when delayed for 4 h after the start of reperfusion. In mice lacking
      the A(2A)AR gene, protection by ATL1465e is lost and ischemic injury of short
      duration is exacerbated compared with wild-type mice, suggesting a protective
      role for endogenous adenosine. I/R injury causes induction of hepatic transcripts
      for IL-1alpha, IL-1beta, IL-1Ra, IL-6, IL-10, IL-18, INF-beta, INF-gamma,
      regulated on activation, normal T cell expressed, and presumably secreted
      (RANTES), major intrinsic protein (MIP)-1alpha, MIP-2, IFN-gamma-inducible
      protein (IP)-10, and monocyte chemotactic protein (MCP)-1 that are suppressed by
      administering ATL146e to wild-type but not to A(2A)AR knockout mice. RANTES, MCP
      1, and IP-10 are notable as induced chemokines that are chemotactic to T
      lymphocytes. The induction of cytokines may contribute to transient lymphopenia
      and neutrophilia that occur after liver I/R injury. We conclude that most damage
      after hepatic ischemia occurs during reperfusion and can be blocked by A(2A)AR
      activation. We speculate that inhibition of chemokine and cytokine production
      limits inflammation and contributes to tissue protection by the A(2A)AR agonist
      ATL146e.

PMID- 14715521
TI  - ET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary
      and nonbiliary cirrhosis in rats.
AB  - Common bile duct ligation (CBDL) triggers a molecular cascade resulting in the
      hepatopulmonary syndrome (HPS). Both increased hepatic endothelin-1 (ET-1)
      production and pulmonary vascular ET(B) receptor expression with stimulation of
      endothelial nitric oxide synthase and TNF-alpha mediated inducible nitric oxide
      synthase and heme oxygenase-1 expression in pulmonary intravascular macrophages
      occur. Whether biliary cirrhosis is unique in triggering ET-1 and TNF-alpha
      alterations and HPS is unknown. We evaluated for HPS in rat prehepatic portal
      hypertension [partial portal vein ligation (PVL)], biliary (CBDL) and nonbiliary
      [thioacetamide treatment (TAA)] cirrhosis, and assessed ET-1 infusion in normal
      and PVL animals. Control, PVL, CBDL, TAA-treated, and ET-1-infused PVL animals
      had ET-1 and TNF-alpha levels measured and underwent molecular and physiological
      evaluation for HPS. HPS developed only in biliary cirrhosis in association with
      increased plasma ET-1 and TNF-alpha levels and the development of established
      molecular changes in the pulmonary microvasculature. In contrast, PVL did not
      increase ET-1 or TNF-alpha levels and TAA treatment increased TNF-alpha levels
      alone, and neither resulted in the full development of molecular or physiological
      changes of HPS despite portal pressure increases similar to those after CBDL.
      Exogenous ET-1 increased TNF-alpha levels and triggered HPS after PVL.
      Combination of ET-1 and TNF-alpha overproduction is unique to biliary cirrhosis
      and associated with experimental HPS. ET-1 infusion increases TNF-alpha levels
      and triggers HPS in prehepatic portal hypertension. ET-1 and TNF-alpha interact
      to trigger pulmonary microvascular changes in experimental HPS.

PMID- 14715522
TI  - Coordinated gastric and sphincter motility evoked by intravenous CCK-8 as
      monitored by ultrasonomicrometry in rats.
AB  - Gastric and sphincter motility evoked by intravenous injection of CCK-8 were
      investigated in urethane-anesthetized rats. Digital ultrasonomicrometry was used
      to monitor pyloric (PYL), antral (ANT), corpus (COR), and lower esophageal
      sphincter (LES) movements while simultaneously measuring intragastric pressure
      (IGP) and, in some experiments, subdiaphragmatic intraesophageal pressure (sIEP).
      Intracrystal distances (ICD) were measured continuously between pairs of
      piezoelectric crystals affixed to the serosa of PYL, ANT, COR (circular and
      longitudinal), and LES. Consecutive intravenous injections of CCK-8 (0.3, 1, and
      3 microg/kg) at 30-min intervals caused dose-dependent simultaneous tonic
      contractions of PYL and ANT, LES opening, and drops in IGP with peak changes at 3
      microg/kg of -17.9 +/- 2.1, -7.7 +/- 2.5, 6.5 +/- 1.4, and -29.2 +/- 3.8%,
      respectively, whereas intravenous saline had no effect. Rhythmic contractile
      activity was inhibited by CCK-8. COR responses were not significantly different
      from vehicle controls for most metrics, and the direction of response for
      circular COR varied between preparations, although not for repeated trials in a
      single preparation. During the LES response to CCK-8, sIEP rose in parallel with
      drops in IGP, indicating formation of a common cavity. Recovery of LES ICD after
      intravenous CCK occurred more rapidly than recovery of PYL ICD, suggesting the
      importance of preventing simultaneous patency of gastroesophageal and
      gastroduodenal passages. The CCK(A) receptor antagonist devazepide (500 microg/kg
      intravenous) inhibited motion responses evoked by intravenous CCK-8. These data
      revealed CCK-8-induced gastric and sphincter activity consistent with
      retropulsion of gastric content.

PMID- 14715523
TI  - Protein kinase C potentiates cAMP-stimulated mouse duodenal mucosal bicarbonate
      secretion in vitro.
AB  - PKC has been shown to regulate epithelial Cl(-) secretion in a variety of models.
      However, the role of PKC in duodenal mucosal bicarbonate secretion is less clear.
      We aimed to investigate the role of PKC in regulation of duodenal mucosal
      bicarbonate secretion. Bicarbonate secretion by murine duodenal mucosa was
      examined in vitro in Ussing chambers using a pH-stat technique. PKC isoform
      expression and activity were assessed by Western blotting and in vitro kinase
      assays, respectively. PMA (an activator of PKC) alone had no effect on duodenal
      bicarbonate secretion or short-circuit current (I(sc)). When PMA and dibutyryl
      cAMP (db-cAMP) were added simultaneously, PMA failed to alter db-cAMP-stimulated
      duodenal bicarbonate secretion or I(sc) (P > 0.05). However, a 1-h preincubation
      with PMA potentiated db-cAMP-stimulated duodenal bicarbonate secretion and I(sc)
      in a concentration-dependent manner (from 10(-8) to 10(-5)M) (P < 0.05). PMA
      preincubation had no effects on carbachol- or heat-stable toxin-stimulated
      bicarbonate secretion. Western blot analysis revealed that PKCalpha, -gamma, 
      epsilon, -, -micro, and -iota/lambda were expressed in murine duodenal mucosa. Ro
      31-8220 (an inhibitor active against PKCepsilon, -alpha, -beta, and -gamma), but
      not Go 6983 (an inhibitor active against PKCalpha, -gamma, -beta, and -delta),
      reversed the potentiating effect of PMA on db-cAMP-stimulated bicarbonate
      secretion. PMA also time- and concentration-dependently increased the activity of
      PKCepsilon, an effect that was prevented by Ro 31-8220 but not Go 6983. These
      results demonstrate that activation of PKC potentiates cAMP-stimulated duodenal
      bicarbonate secretion, whereas it does not modify basal secretion. The effect of
      PKC on cAMP-stimulated bicarbonate secretion is mediated by the PKCepsilon
      isoform.

PMID- 14715524
TI  - Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat
      model of systemic endotoxemia.
AB  - Apoptotic hepatocytes have been demonstrated to represent an important signal for
      transmigration of leukocytes sequestered in sinusoids during endotoxemia in vivo.
      Beside leukocytes, platelets and their adhesion to endothelial cells and
      leukocytes have been implicated in inflammatory liver injury. Using in vivo
      multifluorescence microscopy, we examined the possibility that hepatocellular
      apoptosis causes both leukocytes and platelets to colocalize within the
      sinusoidal microvasculature of endotoxemic livers. We further addressed the issue
      whether cellular colocalization with apoptotic hepatocytes is cause or
      consequence of apoptosis. Intraperitoneal exposure of rats with LPS (5 mg/kg)
      induced liver injury after 6 and 16 h, as given by nutritive perfusion failure
      (20 +/- 2 and 21 +/- 2%), intrahepatic leukocyte (60 +/- 10 and 121 +/- 48
      cells/mm(2)), and platelet (12 +/- 4 and 34 +/- 4 cells/mm(2)) accumulation as
      well as parenchymal cell apoptosis (4 +/- 1 and 11 +/- 2 cells/mm(2)) and caspase
      cleavage (4.7 +/- 2.4- and 7.0 +/- 3.0-fold increase; P < 0.05 vs. saline-exposed
      controls). Higher doses of LPS (10 mg/kg ip) further increased intrahepatic
      leukocyte and platelet accumulation but not the extent of parenchymal apoptosis.
      Detailed spatial analysis revealed colocalization of leukocytes (range 12-24%)
      but barely of platelets (<6%) with apoptotic hepatocytes in all endotoxemic
      groups studied. It is of interest, however, that platelets were found at
      increasing rates in colocalization with leukocytes at 6 and 16 h after LPS
      exposure (5 mg/kg LPS: 7 +/- 3 and 25 +/- 6%; 10 mg/kg LPS: 11 +/- 4 and 14 +/-
      1%). Platelet-leukocyte events significantly correlated with the extent of
      caspase cleavage as an indicator of tissue apoptosis (P < 0.05; r = 0.82).
      Blockade of apoptosis by a pan-caspase inhibitor caused a significant reduction
      of leukocyte adherence and platelet-leukocyte colocalization on LPS exposure. On
      the other hand, leukocytopenic animals revealed reduced hepatocyte apoptosis,
      although values still exceeded those of controls, and in leuko- and
      thrombocytopenic animals, hepatocyte apoptosis was found reduced to control
      values. Taken together, LPS-associated hepatocyte apoptosis seems to be initiated
      by circulating blood cells that become adherent within the liver but might also
      contribute to further sustain the inflammatory cell-cell response.

PMID- 14715525
TI  - Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene
      regulate CDX1 expression in the intestine.
AB  - CDX1 is a homeobox transcription factor that plays a critical role in intestinal
      epithelial cell growth and differentiation. CDX1 gene expression is tightly
      regulated in a temporal and cell-type specific manner. However, very little is
      known about the regulatory mechanisms that direct CDX1 gene expression in the
      intestine. To elucidate these mechanisms, we employed a series of transgenic
      mouse studies using the 5' flanking sequences of the human CDX1 gene. Transgenic
      mice containing nucleotides between -5667 and +68 relative to the transcription
      start site of the CDX1 gene demonstrated ectopic expression of the transgene in
      the brain and gastric smooth muscle. However, transgenic expression of the
      nucleotides -15601 to +68 of the CDX1 gene was restricted to the intestinal
      epithelium, which was identical to endogenous CDX1 gene expression. Taken
      together, the upstream sequences between -15601 and -5667 contain regulatory
      elements that direct transgene expression specifically to the intestinal
      epithelium. Furthermore, DNase I hypersensitivity assays revealed two active
      chromatin regions in the CDX1 gene (hypertensive sites 1 and 2) located at
      approximately -5.8 and -6.8 kb upstream of the CDX1 gene, respectively, which may
      function as potential intestine-specific enhancers.

PMID- 14715526
TI  - Abnormal Paneth cell granule dissolution and compromised resistance to bacterial
      colonization in the intestine of CF mice.
AB  - Paneth cells of intestinal crypts contribute to host defense by producing
      antimicrobial peptides that are packaged as granules for secretion into the crypt
      lumen. Here, we provide evidence using light and electron microscopy that
      postsecretory Paneth cell granules undergo limited dissolution and accumulate
      within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this
      finding, we evaluated bacterial colonization and expression of two major
      constituents of Paneth cells, i.e., alpha-defensins (cryptdins) and lysozyme, in
      CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens
      in both untreated CF mice with impending intestinal obstruction and in CF mice
      treated with an osmotic laxative that prevented overt clinical symptoms and mucus
      accretion. Ultrastructure studies indicated little change in granule morphology
      within mucus casts, whereas granules in laxative-treated mice appear to undergo
      limited dissolution. Protein extracts from CF intestine had increased levels of
      processed cryptdins compared with those from wild-type (WT) littermates.
      Nonetheless, colonization with aerobic bacteria species was not diminished in the
      CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen,
      Salmonella typhimurium, resulted in greater colonization of CF compared with WT
      intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine
      was shown by microarray analysis, real-time quantitative PCR, and Northern blot
      analysis. Based on these findings, we conclude that antimicrobial peptide
      activity in CF mouse intestine is compromised by inadequate dissolution of Paneth
      cell granules within the crypt lumens.

PMID- 14715527
TI  - GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene
      in concert with HNF-1alpha.
AB  - Transcriptional regulation by GATA-4, GATA-5, and GATA-6 in intestine and liver
      was explored using a transgene constructed from the proximal promoter of the rat
      liver fatty acid binding protein gene (Fabpl). An immunohistochemical survey
      detected GATA-4 and GATA-6 in enterocytes, GATA-6 in hepatocytes, and GATA-5 in
      neither cell type in adult animals. In cell transfection assays, GATA-4 or GATA-5
      but not GATA-6 activated the Fabpl transgene solely through the most proximal of
      three GATA binding sites in the Fabpl promoter. However, all three factors
      activated transgenes constructed from each Fabpl site upstream of a minimal viral
      promoter. GATA factors interact with hepatic nuclear factor (HNF)-1alpha, and the
      proximal Fabpl GATA site adjoins an HNF-1 site. GATA-4, GATA-5, or GATA-6 bounded
      to HNF-1alpha in solution, and all cooperated with HNF-1alpha to activate the
      Fabpl transgene. Mutagenizing all Fabpl GATA sites abrogated transgene activation
      by GATA factors, but GATA-4 activated the mutagenized transgene in the presence
      of HNF-1alpha. These in vitro results suggested GATA/HNF-1alpha interactions
      function in Fabpl regulation, and in vivo relevance was determined with
      subsequent experiments. In mice, the Fabpl transgene was active in enterocytes
      and hepatocytes, a transgene with mutagenized HNF-1 site was silent, and a
      transgene with mutagenized GATA sites had identical expression as the native
      transgene. Mice mosaic for biallelic Gata4 inactivation lost intestinal but not
      hepatic Fabpl expression in Gata4-deficient cells but not wild-type cells. These
      results demonstrate GATA-4 is critical for intestinal gene expression in vivo and
      suggest a specific GATA-4/HNF-1alpha physical and functional interaction in Fabpl
      activation.

PMID- 14715528
TI  - Role of IL-10 in regulating proinflammatory cytokine release by Kupffer cells
      following trauma-hemorrhage.
AB  - IL-6 and TNF-alpha production by Kupffer cells is markedly stimulated following
      trauma-hemorrhage (T-H). Because IL-10 is an anti-inflammatory cytokine, the aim
      of this study was to determine whether IL-10 regulates Kupffer cell
      proinflammatory cytokine release following T-H. To study this, we subjected adult
      male Sprague-Dawley rats to sham operation or T-H. The procedure involved a 5-cm
      midline laparotomy and approximately 90 min of hemorrhagic shock (35 mmHg),
      followed by resuscitation with four times the shed blood volume in the form of
      Ringer's lactate. At 2 h after the end of resuscitation, livers were perfused in
      vitro and perfusate was collected. In separate studies, Kupffer cells were
      isolated and incubated with different concentrations of anti-IL-10 MAb. IgG was
      used as control. After 16 h of incubation, IL-6 and TNF-alpha levels were
      measured by ELISA. Plasma IL-10 levels increased significantly following T-H. IL
      10 levels in the perfusate and IL-10 production by cultured Kupffer cells were
      also significantly higher in the T-H group. When Kupffer cells were incubated
      with 10 microg/ml of anti-IL-10 MAb, IL-6 and TNF-alpha production were
      significantly increased in both sham and T-H groups compared with those not
      treated with anti-IL-10 MAb. However, these changes were not observed when the
      cells were incubated with irrelevant (control) IgG. These results indicate that
      IL-10 production by Kupffer cells early after T-H may play a pivotal role in
      attenuating the proinflammatory cytokine environment, possibly in an
      autocrine/paracrine manner.

PMID- 14715530
TI  - Swapping connexin genes: how big is the gap?

PMID- 14715531
TI  - Primary and secondary signaling pathways in early preconditioning that converge
      on the mitochondria to produce cardioprotection.
AB  - Cardioprotective mechanisms such as acute or early preconditioning activate
      several primary signaling pathways that seem to converge on mitochondrial
      targets, leading to altered cell metabolism and inhibition of apoptosis. Acute
      preconditioning leads to generation of agonists, which bind to G protein-coupled
      receptors, and initiates a signaling cascade that involves activation of
      phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, glycogen
      synthase kinase 3beta, mitogen-activated protein kinases, and other signaling
      pathways. Activation of these signaling pathways along with generation of
      reactive oxygen species leads to alterations in the activity of key mitochondrial
      proteins such as mitochondrial ATP-sensitive K(+) channels, the mitochondrial
      permeability transition pore, and bcl-2 family members. Alterations in these
      mitochondrial proteins results in altered metabolism and inhibition of cell
      death, thus resulting in cardioprotection.

PMID- 14715532
TI  - G protein-coupled receptor oligomerization: implications for G protein activation
      and cell signaling.
AB  - The cardiovascular system is richly endowed with G protein-coupled receptors
      (GPCRs), members of the largest family of plasma membrane-localized receptors.
      During the last 10 years, it has become increasingly clear that many, if not all,
      GPCRs function in oligomeric complexes, as either homo- or hetero-oligomers. This
      review explores the mechanistic implications of GPCR dimerization and/or
      oligomerization on receptor activation and interactions with G proteins. The
      effects of GPCR oligomerization on receptor pharmacology, GPCR-mediated
      signaling, and potential contributions to GPCR crosstalk will be considered in
      the context of receptors important in the cardiovascular system. Our evolving
      understanding of the structural and functional consequences of GPCR
      oligomerization may provide novel and more selective sites for pharmacological
      tuning of cardiovascular function.

PMID- 14715529
TI  - ACE, ACE inhibitors, and other JNK.

PMID- 14715534
TI  - Retraction.

PMID- 14715533
TI  - Retraction.

PMID- 14715535
TI  - Abnormal calcium signaling and sudden cardiac death associated with mutation of
      calsequestrin.
AB  - Mutations in human cardiac calsequestrin (CASQ2), a high-capacity calcium-binding
      protein located in the sarcoplasmic reticulum (SR), have recently been linked to
      effort-induced ventricular arrhythmia and sudden death (catecholaminergic
      polymorphic ventricular tachycardia). However, the precise mechanisms through
      which these mutations affect SR function and lead to arrhythmia are presently
      unknown. In this study, we explored the effect of adenoviral-directed expression
      of a canine CASQ2 protein carrying the catecholaminergic polymorphic ventricular
      tachycardia-linked mutation D307H (CASQ2(D307H)) on Ca2+ signaling in adult rat
      myocytes. Total CASQ2 protein levels were consistently elevated approximately 4
      fold in cells infected with adenoviruses expressing either wild-type CASQ2
      (CASQ2(WT)) or CASQ2(D307H). Expression of CASQ2(D307H) reduced the Ca2+ storing
      capacity of the SR. In addition, the amplitude, duration, and rise time of
      macroscopic I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks were
      reduced significantly in myocytes expressing CASQ2(D307H). Myocytes expressing
      CASQ2(D307H) also displayed drastic disturbances of rhythmic oscillations in
      [Ca2+]i and membrane potential, with signs of delayed afterdepolarizations when
      undergoing periodic pacing and exposed to isoproterenol. Importantly, normal
      rhythmic activity was restored by loading the SR with the low-affinity Ca2+
      buffer, citrate. Our data suggest that the arrhythmogenic CASQ2(D307H) mutation
      impairs SR Ca2+ storing and release functions and destabilizes the Ca2+-induced
      Ca2+ release mechanism by reducing the effective Ca2+ buffering inside the SR
      and/or by altering the responsiveness of the Ca2+ release channel complex to
      luminal Ca2+. These results establish at the cellular level the pathological link
      between CASQ2 mutations and the predisposition to adrenergically mediated
      arrhythmias observed in patients carrying CASQ2 defects.

PMID- 14715536
TI  - Protein kinase A phosphorylation at serine-2808 of the cardiac Ca2+-release
      channel (ryanodine receptor) does not dissociate 12.6-kDa FK506-binding protein
      (FKBP12.6).
AB  - Dissociation of FKBP12.6 from the cardiac Ca2+-release channel (RyR2) as a
      consequence of protein kinase A (PKA) hyperphosphorylation of RyR2 at a single
      amino acid residue, serine-2808, has been proposed as an important mechanism
      underlying cardiac dysfunction in heart failure. However, the issue of whether
      PKA phosphorylation of RyR2 can dissociate FKBP12.6 from RyR2 is controversial.
      To additionally address this issue, we investigated the effect of PKA
      phosphorylation and mutations at serine-2808 of RyR2 on recombinant or native
      FKBP12.6-RyR2 interaction. Site-specific antibodies, which recognize the serine
      2808 phosphorylated or nonphosphorylated form of RyR2, were used to unambiguously
      correlate the phosphorylation state of RyR2 at serine-2808 with its ability to
      bind FKBP12.6. We found that FKBP12.6 can bind to both the serine-2808
      phosphorylated and nonphosphorylated forms of RyR2. The S2808D mutant thought to
      mimic constitutive phosphorylation also retained the ability to bind FKBP12.6.
      Complete phosphorylation at serine-2808 by exogenous PKA disrupted neither the
      recombinant nor native FKBP12.6-RyR2 complex. Furthermore, binding of site
      specific antibodies to the serine-2808 phosphorylation site did not dissociate
      FKBP12.6 from or prevent FKBP12.6 from binding to RyR2. Taken together, our
      results do not support the notion that PKA phosphorylation at serine-2808
      dissociates FKBP12.6 from RyR2.

PMID- 14715537
TI  - Assignment of Neisseria meningitidis serogroups A, C, W135, and Y anticapsular
      total immunoglobulin G (IgG), IgG1, and IgG2 concentrations to reference sera.
AB  - Meningococcal serogroup-specific immunoglobulin G (IgG), IgG1, and IgG2
      concentrations were assigned to three reference sera, CDC 1992, 89-SF, and
      96/562, for meningococcal serogroups A, C, Y, and W135 via the method of cross
      standardization. The sum of the serogroup-specific IgG1 and IgG2 concentrations
      determined for the four meningococcal serogroups showed good agreement with the
      serogroup-specific IgG either determined here or as previously represented.
      Following the assignment of meningococcal serogroup-specific IgG1 and IgG2
      concentration to these reference sera, a meningococcal serogroup-specific IgG1
      and IgG2 enzyme-linked immunosorbent assay protocol was developed. The serogroup
      A and C specific subclass distribution of a panel of adult sera collected
      following vaccination with any combination of meningococcal serogroup C
      conjugate, bivalent, or tetravalent polysaccharide vaccines was determined. For
      the determination of serogroup W135 and Y specific subclass distribution, an
      adolescent panel 28 days following a single dose of either tetravalent
      polysaccharide or conjugate vaccine was used. The sum of the serogroup-specific
      IgG1 and IgG2 showed strong correlation with the serogroup-specific total IgG
      determined. The assignment here of IgG1 and IgG2 subclasses to these reference
      sera will allow more detailed evaluation of meningococcal conjugate and
      polysaccharide vaccines.

PMID- 14715538
TI  - Relationship of binding of immunoglobulin G to Plasmodium falciparum-infected
      erythrocytes with parasite endemicity and antibody responses to conserved antigen
      in immune individuals.
AB  - To investigate the potential for use of a well-established strain of Plasmodium
      falciparum as a reference strain for infected red blood cell (IRBC) surface
      reactivity, we monitored the binding of specific immunoglobulin G (IgG) from
      immune individuals to the reference Knob-positive FCR3 strain by flow cytometry.
      To permit interassay comparison for 162 plasma samples drawn after the rainy
      season, a labeling index (LI) was defined as the percentage of labeled parasites
      multiplied by the mean peak intensity. An LI ratio (LIR) was then calculated as
      the LI of the sample divided by the LI of the control. LIRs were calculated for
      individuals living in Dielmo and Ndiop, two Senegalese villages where P.
      falciparum is transmitted holoendemically and mesoendemically, respectively. The
      incidence (persons with an LIR of >3) observed in Dielmo was lower than that
      observed in Ndiop. Significantly higher LIRs were observed (i) for samples from
      Ndiop than for samples from Dielmo (P < 0.01) and (ii) in Ndiop, in subjects with
      hemoglobin AS (HbAS) than in those with hemoglobin AA (P = 0.03). No correlation
      with the cumulative age-associated immune status of the villagers was evidenced,
      contrary to antibody (Ab) responses against conserved IRBC-associated antigen
      (Ag) measured by enzyme-linked immunosorbent assay. These results are consistent
      with the notions that protection in HbAS individuals may relate to an increased
      IgG response to IRBC membrane Ags and that cell surface reactivity parallels IgG
      responses even though it is in itself a distinct indicator of the anti-P.
      falciparum Ab response. Measures of IgG binding to live IRBC are thus relevant
      for the functional screening of conserved IRBC-associated Ags that contribute to
      parasite destruction in vivo, as these Ags might be included in a multitarget
      vaccine.

PMID- 14715539
TI  - Magnitude of serum and intestinal antibody responses induced by sequential
      replicating and nonreplicating rotavirus vaccines in gnotobiotic pigs and
      correlation with protection.
AB  - A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human
      rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus
      protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown
      to be effective for induction of intestinal antibody-secreting cell (ASC)
      responses and protection in gnotobiotic pigs. Because serum or fecal antibody
      titers, but not intestinal ASC responses, can be used as potential markers of
      protective immunity in clinical vaccine trials, we determined the serum and
      intestinal antibody responses to this prime-boost rotavirus vaccine regimen and
      the correlations with protection. Gnotobiotic pigs were vaccinated with one of
      the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination
      (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a
      mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were
      also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral
      doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs
      in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A
      (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05)
      intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers
      postchallenge compared to those in the other groups. Statistical analyses of the
      correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers
      and protection demonstrated that each of these was an indicator of protective
      immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA
      and not IgM or IgG antibody titers in serum were highly correlated (R2 = 0.89; P
      < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines
      among all the vaccinated groups, indicating that the IgA antibody titer is
      probably the most reliable indicator of protection.

PMID- 14715540
TI  - Phenotypic drug susceptibility assay for influenza virus neuraminidase
      inhibitors.
AB  - A flow cytometric (fluorescence-activated cell sorter [FACS]) assay was developed
      for analysis of the drug susceptibilities of wild-type and drug-resistant
      influenza A and B virus laboratory strains and clinical isolates for the
      neuraminidase (NA) inhibitors oseltamivir carboxylate, zanamivir, and peramivir.
      The drug susceptibilities of wild-type influenza viruses and those with mutations
      in the hemagglutinin (HA) and/or NA genes rendering them resistant to one or more
      of the NA inhibitors were easily determined with the FACS assay. The drug
      concentrations that reduced the number of virus-infected cells or the number of
      PFU by 50% as determined by the FACS assay were similar to those obtained with
      the more time-consuming and labor-intensive virus yield reduction assay. The NA
      inhibition (NAI) assay confirmed the resistance patterns demonstrated by the FACS
      and virus yield assays for drug-resistant influenza viruses with mutations in the
      NA gene. However, only the FACS and virus yield assays detected NA inhibitor
      resistant influenza viruses with mutations in the HA gene but not in the NA gene.
      The FACS assay is more rapid and less labor-intensive than the virus yield assay
      and just as quantitative. The FACS assay determines the drug susceptibilities of
      influenza viruses with mutations in either the HA or NA genes, making the assay
      more broadly useful than the NAI assay for measuring the in vitro
      susceptibilities of influenza viruses for NA inhibitors. However, since only
      viruses with mutations in the NA gene that lead to resistance to the NA
      inhibitors correlate with clinical resistance, this in vitro assay should not be
      used in the clinical setting to determine resistance to NA inhibitors. The assay
      may be useful for determining the in vivo susceptibilities of other compounds
      effective against influenza A and B viruses.

PMID- 14715541
TI  - Population-based hematologic and immunologic reference values for a healthy
      Ugandan population.
AB  - To assess the validity of the reference values for hematologic and immunologic
      indices currently used in Africa, we evaluated blood samples from 3,311 human
      immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years.
      Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all
      significantly increased with age (P < 0.001) and were independent of gender until
      the age of 13 years, after which the levels were higher in males than in females
      (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte
      counts significantly declined with age until the age of 13 years (P < 0.001),
      with no differences by gender, while platelet counts declined with age (P <
      0.001) and showed differences by gender only among adults older than age 24
      years. CD4+- and CD8+-cell counts declined with age until the age of 18 years;
      thereafter, females had higher counts than males. The absolute values for many of
      these parameters differed from those reported for populations outside Africa,
      suggesting that it may be necessary to develop tables of reference values for
      hematologic and immunologic indices specific for the African population. This may
      be particularly important with regard to CD4+-cell counts among children because
      significant differences in absolute and percent CD4+-cell counts exist between
      the values for Western populations and the values for the population evaluated in
      our study. These differences could influence the decision to initiate
      antiretroviral therapy among children infected with HIV.

PMID- 14715542
TI  - Neutralization of gamma interferon augments borreliacidal antibody production and
      severe destructive Lyme arthritis in C3H/HeJ mice.
AB  - Development of a high level of sustained borreliacidal antibody is paramount for
      maintaining protection against infection with Borrelia burgdorferi. We show that
      production of borreliacidal antibody can be enhanced by preventing the effects of
      gamma interferon (IFN-gamma). When lymph node cells capable of producing
      borreliacidal antibody were cultured with anti-murine IFN-gamma, an eightfold
      increase in borreliacidal antibody production was obtained. However, anti-IFN
      gamma treatment of these cells also enhanced their ability to adaptively induce
      arthritis. When anti-IFN-gamma-treated lymph node cells producing borreliacidal
      antibody were infused into C3H/HeJ mice and the mice were then challenged with B.
      burgdorferi, the mice developed severe destructive Lyme arthritis. Additional
      studies are needed to delineate the immune response responsible for the induction
      of arthritis and production of borreliacidal antibody. These studies are needed
      to ensure an effective and safe vaccine against infection with B. burgdorferi.

PMID- 14715543
TI  - Performance and use of a ribonucleotide reductase herpes simplex virus type
      specific serological assay.
AB  - In response to the increasingly evident need for herpes simplex virus (HSV)
      serotype-specific serologic assays that rely on proteins other than glycoprotein
      G (gG), we developed a rapid serologic assay that is based on type-specific
      epitopes within the large subunit of HSV ribonucleotide reductase (R1). The assay
      (Au-2 enzyme-linked immunosorbent assay [ELISA]) uses an HSV type 2 (HSV-2) R1
      peptide antigen. It provides a reliable method for detecting serotype-specific
      antibody to a protein other than gG-2. The Au-2 ELISA has high sensitivity and
      specificity as determined by direct comparison to Western blotting, a widely
      accepted "gold standard," and to ELISA with an HSV-1 R1 peptide (Au-1). The use
      of the Au-2 ELISA in conjunction with the gG-2-based assays will improve the
      sensitivity and specificity of serologic diagnosis and patient management.

PMID- 14715544
TI  - Comparison of a multiplexed fluorescent covalent microsphere immunoassay and an
      enzyme-linked immunosorbent assay for measurement of human immunoglobulin G
      antibodies to anthrax toxins.
AB  - Recently, the Centers for Disease Control and Prevention reported an accurate,
      sensitive, specific, reproducible, and quantitative enzyme-linked immunosorbent
      assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis
      protective antigen (PA) in human serum (C. P. Quinn, V. A. Semenova, C. M. Elie
      et al., Emerg. Infect. Dis. 8:1103-1110, 2002). The ELISA had a minimum
      detectable concentration (MDC) of 0.06 microgram/ml, which, when dilution
      adjusted, yielded a whole-serum MDC of 3.0 micro g of anti-PA IgG per ml. The
      reliable detection limit (RDL) was 0.09 microgram/ml, while the dynamic range was
      0.06 to 1.7 microgram/ml. The diagnostic sensitivity of the assay was 97.6% and
      the diagnostic specificity was 94.2% for clinically verified cases of anthrax. A
      competitive inhibition anti-PA IgG ELISA was also developed to enhance the
      diagnostic specificity to 100%. We report a newly developed fluorescence covalent
      microbead immunosorbent assay (FCMIA) for B. anthracis PA which was Luminex xMap
      technology. The FCMIA MDC was 0.006 microgram of anti-PA IgG per ml, the RDL was
      0.016 microgram/ml, and the whole-serum equivalent MDC was 1.5 micrograms/ml. The
      dynamic range was 0.006 to 6.8 microgram/ml. Using this system, we analyzed 20
      serum samples for anti-PA IgG and compared our results to those measured by ELISA
      in a double-masked analysis. The two methods had a high positive correlation (r2
      = 0.852; P < 0.001). The FCMIA appears to have benefits over the ELISA for the
      measurement of anti-PA IgG, including greater sensitivity and speed, enhanced
      dynamic range and reagent stability, the use of smaller sample volumes, and the
      ability to be multiplexed (measurement of more than one analyte simultaneously),
      as evidenced by the multiplexed measurement in the present report of anti-PA and
      anti-lethal factor IgG in serum from a confirmed clinical anthrax infection.

PMID- 14715545
TI  - Important role of P-selectin for leukocyte recruitment, hepatocellular injury,
      and apoptosis in endotoxemic mice.
AB  - Leukocyte recruitment in the liver includes a two-step procedure in which
      selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18
      dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles
      of the individual selectins in leukocyte rolling and adhesion, hepatocellular
      injury, and apoptosis remain elusive. Therefore, we examined the
      pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged
      with lipopolysaccharide (LPS) and D-galactosamine (Gal) by use of intravital
      microscopy of the liver microcirculation. In control animals, administration of
      LPS-Gal provoked reproducible hepatic damage, including marked increases of
      leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced
      sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin
      antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and
      71%, respectively. Moreover, interference with P-selectin function significantly
      improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to
      84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of
      apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in
      RB40.34-treated animals. In contrast, administration of an anti-E-selectin
      antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect
      against endotoxin-induced leukocyte responses or hepatic injury. In conclusion,
      our novel findings document a principal role of P-selectin in mediating leukocyte
      rolling, a precondition to the subsequent firm adhesion of leukocytes in liver
      injury. Furthermore, our novel data demonstrate that inhibition of P-selectin
      function reduces hepatocellular injury and apoptosis, suggesting a causal
      relationship between leukocyte recruitment on one hand and hepatocellular injury
      and apoptosis on the other hand. Based on these findings, it is suggested that P
      selectin may be an important therapeutic target in endotoxin-induced liver
      injury.

PMID- 14715546
TI  - Inhibition of prostate cancer cell colony formation by the flavonoid quercetin
      correlates with modulation of specific regulatory genes.
AB  - The natural product quercetin is a flavonoid found in many fruits and vegetables.
      Previous research has shown that quercetin has antitumor, anti-inflammatory,
      antiallergic, and antiviral activities. In the present investigation we studied
      the effect of quercetin on the ability of prostate cancer cell lines with various
      degrees of aggressive potential to form colonies in vitro. Specifically, we
      examined the molecular mechanisms underlying this effect, including the
      expression of cell cycle and tumor suppressor genes as well as oncogenes. We
      observed that quercetin at concentrations of 25 and 50 micro M significantly
      inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and
      the moderately aggressive DU-145 prostate cancer cell line, whereas it did not
      affect colony formation by the poorly aggressive LNCaP prostate cancer cell line
      or the normal fibroblast cell line BG-9. Using the gene array methodology, we
      found that quercetin significantly inhibited the expression of specific oncogenes
      and genes controlling G(1), S, G(2), and M phases of the cell cycle. Moreover,
      quercetin reciprocally up-regulated the expression of several tumor suppressor
      genes. In conclusion, our results demonstrate that the antitumor effects of
      quercetin directly correlate with the aggressive potential of prostate cancer
      cells and that the mechanism(s) of quercetin-mediated antitumor effects may
      involve up-regulation of tumor suppressor genes and reciprocal down-regulation of
      oncogenes and cell cycle genes. The results of these studies provide a scientific
      basis for the potential use of flavonoids as nutraceuticals in the
      chemoprevention of cancer.

PMID- 14715547
TI  - Comparison of antibody responses to a potential combination of specific
      glycolipids and proteins for test sensitivity improvement in tuberculosis
      serodiagnosis.
AB  - The humoral response to different proteinaceous antigens of Mycobacterium
      tuberculosis is heterogeneous among patients with active disease, and this has
      originated in the proposal to use a combination of several specific antigens to
      find an efficient serodiagnostic test for tuberculosis (TB). However, to date,
      comparisons of antibody responses to several antigens in the same population have
      been carried out without consideration of antigenic cell wall glycolipids. In the
      present study the presence of immunoglobulin G (IgG), IgM, and IgA antibodies to
      M. tuberculosis glycolipids (sulfolipid I, diacyltrehaloses, triacyltrehaloses,
      and cord factor) was compared with the response to four commercially available
      tests based on the 38-kDa protein mixed with the 16-kDa protein or
      lipoarabinomannan. Fifty-two serum samples from TB patients and 83 serum samples
      from control individuals (48 healthy individuals and 35 non-TB pneumonia
      patients) were studied. Three relevant results were obtained. (i) Smear-negative
      TB patients presented low humoral responses, but the sera which did react
      principally showed IgA antibodies to some glycolipidic antigens. (ii) TB patients
      exhibit heterogeneous humoral responses against glycolipidic antigens. (iii)
      Finally, test sensitivity is improved (from 23 to 62%) when IgG and IgA
      antibodies are detected together in tests based on different antigens (proteins
      and glycolipids). We conclude that it is possible to include glycolipidic
      antigens in a cocktail of specific antigens from M. tuberculosis to develop a
      serodiagnostic test.

PMID- 14715548
TI  - Calcium signaling through phospholipase C activates dendritic cells to mature and
      is necessary for the activation and maturation of dendritic cells induced by
      diverse agonists.
AB  - Calcium is an important second messenger in the phospholipase C (PLC) signal
      transduction pathway. Calcium signaling is involved in many biological processes,
      including muscle contraction, cellular activation, and cellular proliferation.
      Dendritic cell (DC) maturation is induced by many different stimuli, including
      bacterial lipopolysaccharide (LPS), bacterial toxins, inflammatory cytokines,
      prostaglandins, as well as calcium mobilization. In the present study, we
      determined the role of the PLC signal transduction pathway in the activation and
      maturation of human monocyte-derived DCs (MDDCs) induced by diverse agonists. We
      found that signaling through PLC activates MDDCs to mature and is necessary for
      LPS, cholera toxin, dibutyryl-cyclic AMP, prostaglandin E2, and the calcium
      ionophore A23187 to induce MDDC maturation. The results of the present study
      along with the results of other studies indicate that multiple signaling pathways
      are involved in the activation of DCs and that inhibition of any of these
      pathways inhibits the maturation of DCs.

PMID- 14715549
TI  - Immunologic hyporesponsiveness to serogroup C but not serogroup A following
      repeated meningococcal A/C polysaccharide vaccination in Saudi Arabia.
AB  - In Saudi Arabia, vaccination with the meningococcal A/C polysaccharide (MACP)
      vaccine is advised every 3 years. A clinical outcome study was performed to test
      the effect of repeat vaccination with the MACP vaccine on the immune responses
      among Saudi nationals who live in the Makkah and Jeddah areas. Subjects (n = 230)
      aged 10 to 29 years were selected: 113 subjects with two or more prior
      vaccinations with the MACP vaccine, 79 subjects with one prior vaccination with
      the MACP vaccine, and 38 subjects naive to vaccination with the MACP vaccine. All
      subjects received the MACP vaccine in 2002, and serum bactericidal antibody (SBA)
      titers were measured before and 1 month after vaccination with the MACP vaccine.
      For serogroup C, geometric mean SBA titers 1 month following vaccination with the
      MACP vaccine were 708.6 (95% confidence interval [CI], 217.5 to 2,308.9) for
      those naive to prior vaccination with the MACP vaccine, and they were
      significantly higher (P < 0.0001) than 25.0 (95% CI, 12.4 to 50.2) for those who
      had received one prior vaccination with the MACP vaccine and 32.4 (95% CI, 18.7
      to 56.4) for those who had received two or more doses of the MACP vaccine. For
      serogroup A, the geometric mean SBA titer 1 month after receipt of the MACP
      vaccine was 1,649.3 (95% CI, 835.2 to 3,256.9) for those naive to prior
      vaccination, and the titers were lower (P = 0.67) than 2,185.7 (95% CI, 1,489.4
      to 3,207.7) for those who had received one prior dose of the MACP vaccine and
      significantly lower (P = 0.042) than 3,540.8 (95% CI, 2,705.2 to 4,634.5) for
      those who had received two or more doses of the MACP vaccine. For serogroup C,
      the proportions of nonresponders (SBA titers, <8) were 19% for the naive cohort,
      52% for the cohort with one prior vaccination, and 49% for the cohort with two or
      more prior vaccinations. Following repeated doses of the MACP vaccine,
      hyporesponsiveness to serogroup C is evident, with high percentages of MACP
      vaccinees having SBA titers below the putative protective SBA titer. Serogroup A
      responses following vaccination with the MACP vaccine were boosted. Introduction
      of the serogroup C conjugate vaccine would provide long-term protection against
      serogroup C disease; however, quadrivalent conjugate vaccines are required to
      provide long-time protection against disease caused by serogroups A, W135, and Y.

PMID- 14715550
TI  - Measurement of serum bactericidal activity specific for Haemophilus influenzae
      type b by using a chromogenic and fluorescent metabolic indicator.
AB  - We evaluated alamarBlue as a metabolic indicator in a standardized assay for the
      measurement of serum bactericidal activity (SBA) to Haemophilus influenzae type b
      (Hib) using sera containing natural and vaccine-induced anticapsular
      (polyribosylribitol phosphate) antibodies. SBA assays with a colorimetric and a
      fluorometric end point in the presence of alamarBlue were developed and compared
      to a standard SBA assay, where colony counts are performed to determine the titer
      (12). A colorimetric end point required a spectrophotometer, whereas a
      fluorometric end point required a fluorometer. Prevaccination sera (n = 27) and
      postvaccination sera (n = 13) were tested by all three methodologies, and the SBA
      titers obtained in the presence of alamarBlue were compared to those from the
      standard method. Both the colorimetric and the fluorometric SBA titers were
      significantly correlated (r = 0.87 and r = 0.95, respectively) with those of the
      standard assay (>/= 50% killing as the SBA titer end point), and titers were not
      significantly different when compared to those of the standard assay (P > 0.68).
      However, the fluorometric end point had superior performance and ease of titer
      determination compared to the colorimetric end point (95 versus 87% of SBA titers
      were within 2 dilutions of the standard titer). Hib SBA assays with alamarBlue
      are reproducible, faster (same-day assay), and easier to perform than the
      standardized assay, which requires manual or automated colony counts. These
      semiautomated methodologies result in increased sample throughput and collection
      of data in digital formats that can be exported to data analysis programs for
      determination of SBA titers.

PMID- 14715551
TI  - Immunoglobulin A (IgA) and IgG immune responses against P-90 antigen for
      diagnosis of pulmonary tuberculosis and screening for Mycobacterium tuberculosis
      infection.
AB  - The purpose of the present study was to evaluate the usefulness of detection of
      serum immunoglobulin A (IgA) and IgG antibodies directed against the
      mycobacterial P-90 antigen for the diagnosis of active pulmonary tuberculosis
      (PTB) among symptomatic individuals and for the detection of Mycobacterium
      tuberculosis infections among close contacts of PTB patients. Two commercially
      available enzyme immunoassay (EIA) kits (IgA EIA-TB [EIA-IgA] and IgG EIA-TB [EIA
      IgG]; Kreatech Diagnostics) were evaluated in a blinded fashion by using stored
      serum samples from 268 individuals, including 69 patients with PTB, 41 patients
      with diseases other than tuberculosis (TB), 12 subjects with healed PTB, 39 close
      contacts of PTB patients, and 107 healthy volunteers. For the EIA-IgA, the
      sensitivity was 74% and the specificity was 68% when a cutoff determined by a
      receiver operator characteristic curve was used. For the EIA-IgG, the sensitivity
      was 69% and the specificity was 64%. The EIA-IgA was positive for 54% of healthy
      close contacts of PTB patients but only 8% of healthy controls without contact
      with a PTB patient or a prior personal history of TB (P < 0.001). The relatively
      low sensitivities and specificities of these serologic tests make them poor tools
      for the diagnosis of PTB among patients with suspected PTB. However, the
      relatively high prevalence of positive EIA-IgA results among healthy close
      contacts of PTB patients warrants further evaluation of this test with close
      contacts and other populations at risk for recent M. tuberculosis exposure and
      development of disease.

PMID- 14715552
TI  - Evaluation of the Determine Rapid Syphilis TP assay using sera.
AB  - The Abbott Determine Rapid Syphilis TP assay is a treponemal test that can be
      used in resource-poor settings that lack laboratory facilities. However, this
      test has not been extensively evaluated. We measured its sensitivity and
      specificity by using stored serum specimens (n = 567) from all persons who tested
      Treponema pallidum hemagglutination assay (TPHA) positive (n = 250) or TPHA
      indeterminate (n = 17) in the year 2001 and the first 300 patients in 2001 who
      tested TPHA negative at the Evandro Chagas Research Institute in Rio de Janeiro,
      Brazil. This rapid assay was independently interpreted by three different
      observers. With TPHA results as the reference, sensitivity ranged between readers
      from 95.6 to 98.4% and specificity ranged from 97.3 to 95.7%. There was little
      interreader variability in the interpretation of results, with approximately 98%
      agreement for all reader combinations. Of samples from persons with human
      immunodeficiency virus (HIV) infection (n = 198), sensitivity was 96.9 to 99.2%
      and it was 94.4 to 96.3% among HIV-negative persons (n = 127). Specificity was
      92.4 to 95.5% among HIV-positive persons and 97.2 to 100% among HIV-negative
      persons. We found this test to have high sensitivity and specificity and little
      interreader variability, indicating that it may be easily used in resource-poor
      settings without laboratory facilities. Further studies are needed using this
      test on whole blood and under the clinical conditions for which it is intended.

PMID- 14715553
TI  - Fecal immunoglobulin A antibodies in dogs infected or vaccinated with canine
      coronavirus.
AB  - Fecal secretory immunoglobulin A (IgA) antibodies in dogs infected or vaccinated
      with canine coronavirus (CCV) were evaluated by an enzyme-linked immunosorbent
      assay. The study was carried out with 32 fecal samples collected just before
      inoculation and at 28 days postinoculation. Five groups were studied: naturally
      infected dogs, experimentally infected dogs, dogs inoculated with a modified live
      (ML) CCV vaccine by the intramuscular route, dogs inoculated with an ML CCV
      vaccine by the oronasal route, and dogs given an inactivated CCV vaccine. Both
      the naturally and the experimentally infected dogs developed high levels of fecal
      IgAs. Interestingly, dogs inoculated with the ML CCV vaccine by the oronasal
      route developed levels of fecal IgA that were higher than those observed in the
      dogs inoculated with the same CCV vaccine by the intramuscular route or those
      observed in dogs inoculated with the inactivated vaccine. A relationship between
      the level of fecal IgAs to CCV and the degree of protection against CCV infection
      was observed.

PMID- 14715554
TI  - Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL
      12) and IL-18 do not augment infection-stimulated bone resorption in vivo.
AB  - Periapical granulomas are induced by bacterial infection of the dental pulp and
      result in destruction of the surrounding alveolar bone. In previous studies we
      have reported that the bone resorption in this model is primarily mediated by
      macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is
      in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the
      present study, the functional roles of the Th1 cytokine gamma interferon (IFN
      gamma) and IFN-gamma-inducing cytokines IL-12 and IL-18 were determined in a
      murine model of periapical bone destruction. IL-12-/-, IL-18-/-, and IFN-gamma-/-
      mice were subjected to surgical pulp exposure and infection with a mixture of
      four endodontic pathogens, and bone destruction was determined by microcomputed
      tomography on day 21. The results indicated that all IL-12-/-, IL-18-/-, and IFN
      gamma-/- mice had similar infection-stimulated bone resorption in vivo as wild
      type control mice. Mice infused with recombinant IL-12 also had resorption
      similar to controls. IFN-gamma-/- mice exhibited significant elevations in IL-6,
      IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type
      mice, but these modulations had no net effect on IL-1alpha levels. Recombinant IL
      12, IL-18, and IFN-gamma individually failed to consistently modulate macrophage
      IL-1alpha production in vitro. We conclude that, at least individually,
      endogenous IL-12, IL-18, and IFN-gamma do not have a significant effect on the
      pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible
      functional redundancy in proinflammatory pathways.

PMID- 14715555
TI  - Antibody reactivity to Omp31 from Brucella melitensis in human and animal
      infections by smooth and rough Brucellae.
AB  - Group 3 of outer membrane proteins (OMPs) of Brucella includes Omp25 and Omp31,
      which share 34% identity. Omp25 is highly conserved in Brucella species, and
      Omp31 is present in all Brucella species, except Brucella abortus. Antibodies to
      Brucella melitensis Omp31 have been sought only in infected sheep, and Western
      blotting of sera from infected sheep did not reveal anti-Omp31 reactivity. We
      obtained recombinant purified Omp31 (B. melitensis) and tested its recognition by
      sera from humans and animals suffering from brucellosis by an indirect enzyme
      linked immunosorbent assay (ELISA). Serum samples from 74 patients, 57 sheep, and
      47 dogs were analyzed; brucellosis was confirmed by bacteriological isolation in
      all ovine and canine cases and 31 human cases of brucellosis. Thirty-five
      patients (47%) were positive for antibodies to Omp31, including seven cases of
      Brucella suis infection, two cases of B. abortus infection, and three cases of B.
      melitensis infection. Of 39 sheep naturally infected with B. melitensis (biovars
      1 and 3), 23 (59%) were positive for antibodies to Omp31. Anti-Omp31 antibodies
      were also detected in 12 of 18 rams (67%) in which Brucella ovis was isolated
      from semen. Antibodies to Omp31 were also found in 41 (87%) of the 47 dogs,
      including 13 with recent infection. These results suggest that an indirect ELISA
      using recombinant purified Omp31 from B. melitensis would be of limited value for
      the diagnosis of human and animal brucellosis. Nevertheless, the potential
      usefulness of this antigen in combination with other recombinant proteins from
      Brucella should not be dismissed.

PMID- 14715556
TI  - High prevalence of seropositivity to a major allergen of Anisakis simplex, Ani s
      1, in dyspeptic patients.
AB  - Finding evidence of anisakidosis requires invasive methods. We have developed a
      serological assay based on the detection of an immunoglobulin E (IgE)
      specifically directed against Ani s 1 protein, a major parasite allergen of
      Anisakis simplex, which has shown a high level of accuracy in the diagnosis of
      anisakidosis. We used this tool to determine the prevalence of anti-Ani s 1 IgE
      in dyspeptic patients and to investigate if its seropositivity could be related
      to epidemiological factors other than raw fish consumption. A total of 174
      dyspeptic patients who submitted to upper digestive tract endoscopy were studied.
      Specific IgE against Ani s 1 was determined by immunoblotting. Quantitative
      information on smoking, alcohol consumption, and fish consumption as well as a
      history of gastric surgery was recorded. Twenty-four (13.8%) patients were
      seropositive for Ani s 1 protein. The seroprevalence of anti-Ani s 1 IgE
      increased with age in patients who were less than 62 years old (P = 0.047).
      Seropositivity to Ani s 1 was associated with the consumption of fish in vinegar
      (P < 0.001), raw fish (P = 0.001), and smoked fish (P = 0.007). There was no
      relationship between anti-Ani s 1 IgE seropositivity and the number of cigarettes
      smoked (P = 0.098) or alcohol intake (P = 0.179). Five patients had undergone
      previous gastric surgery, and three of those patients were seropositive for Ani s
      1 (P = 0.019). In multivariate analysis, the consumption of fish in vinegar (P =
      0.006), raw fish (P = 0.017), and smoked fish (P = 0.002) and a history of
      gastric surgery (P = 0.005) were independent factors associated with anti-Ani s 1
      IgE detection. In conclusion, at present, anisakidosis might frequently be
      underdiagnosed, and it might have a clinical role in patients with upper
      dyspeptic symptoms. Uncooked-fish ingestion and previous gastric surgery were
      associated with seropositivity for Ani s 1 protein.

PMID- 14715557
TI  - Identification of primary and secondary measles vaccine failures by measurement
      of immunoglobulin G avidity in measles cases during the 1997 Sao Paulo epidemic.
AB  - Despite almost universal use of measles vaccines in recent decades, epidemics of
      the disease continue to occur. Understanding the role of primary vaccine failure
      (failure to seroconvert after vaccination) and secondary vaccine failures (waning
      immunity after seroconversion) in measles epidemics is important for the
      evaluation of measles control programs in developing countries. After a measles
      epidemic in Sao Paulo, Brazil, 159 cases previously confirmed by detection of
      specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a
      secondary immune response, defined by an IgG avidity index of at least 30%, was
      established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%)
      had not been vaccinated and 52 (32.7%) had received one or more doses of measles
      vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune
      response, defined as an IgG avidity index of less than 30%. Among the 52 patients
      with documented vaccination, 25 (48.1%) showed a primary immune response and 27
      (51.9%) showed a secondary immune response, thereby constituting a secondary
      vaccine failure. Primary vaccine failure was observed in 13 of 13 patients
      vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of
      patients receiving one or two doses after their first birthdays. These results
      provide evidence that measurement of IgG avidity can be used to distinguish
      between primary and secondary vaccine failures in vaccinated patients with
      measles; the method can also be a useful tool for the evaluation of measles
      control programs.

PMID- 14715558
TI  - Maintenance of serum immunoglobulin G antibodies to Epstein-Barr virus (EBV)
      nuclear antigen 2 in healthy individuals from different age groups in a Japanese
      population with a high childhood incidence of asymptomatic primary EBV infection.
AB  - Immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) nuclear antigens 2
      and 1 (EBNA-2 and EBNA-1, respectively) were studied using sera from healthy
      individuals of a population with a high incidence of asymptomatic primary EBV
      infections during infancy or childhood in Japan. Two CHO-K1 cell lines expressing
      EBNA-2 and EBNA-1 were used for anticomplement and indirect immunofluorescence
      assays. The positivity rate for EBNA-2 IgG rose in the 1- to 2-year age group,
      increased and remained at a plateau ( approximately 45%) between 3 and 29 years
      of age (3- to 4-, 5- to 9-, 10- to 14-, and 15- to 29-year age groups), and then
      reached 98% by age 40 (>/== 40-year age group). Both seropositivity for EBNA-1
      and seropositivity for EBNAs in Raji cells (EBNA/Raji) were detected in the 1- to
      2-year age group, remained high, and finally reached 100% by age 40. The
      geometric mean titer (GMT) of EBNA-2 IgG reached a plateau in the 5- to 9- and 10
      to 14-year-old groups and remained elevated in the older age groups (15 to 29
      and >/== 40 years). The GMT of EBNA-1 IgGs increased to a plateau in the 1- to 2
      year-old group and remained unchanged in the older age groups. The GMT of
      EBNA/Raji IgGs also reached a plateau in the 1- to 2-year-old group, remained
      level throughout the 3- to 14-year age groups, and decreased in the 15- to 29
      year-olds. EBNA-2 IgGs emerged earlier than EBNA-1 IgGs in 8 of 10 patients with
      infectious mononucleosis, who were between 1 and 27 years old, and declined with
      time in three of eight cases. These results suggest that EBNA-2 IgG antibodies
      evoked in young children by asymptomatic primary EBV infections remain elevated
      throughout life, probably because of reactivation of latent and/or exogenous EBV
      superinfection.

PMID- 14715559
TI  - Simultaneous detection and differentiation of anti-Helicobacter pylori antibodies
      by flow microparticle immunofluorescence assay.
AB  - Helicobacter pylori is the key pathogen for gastroduodenal diseases. The clinical
      outcome of H. pylori infection is influenced by the presence of strain-specific
      virulence factors that are usually detected by the presence of specific anti-H.
      pylori antibodies in serum. Apart from the detection of these antibodies by
      enzyme-linked immunosorbent assay (ELISA), it is desirable to obtain additional
      information concerning the presence of certain virulence factors of H. pylori
      that are currently detected by immunoblot analysis. At present, the
      immunodiagnosis of an H. pylori infection includes two separate methods: ELISA
      and immunoblot analysis. Here, we report the development and evaluation of a new
      rapid flow microparticle immunofluorescence assay (FMIA) for detection of anti-H.
      pylori antibodies in human serum. The assay allows rapid qualitative and
      quantitative detection of anti-H. pylori antibodies by using crude antigen
      preparations as well as single recombinant antigens (urease A, urease B, CagA,
      and alkylhydroxy peroxide reductase) in the same sample with one measurement, and
      thus it combines the advantages of enzyme immunoassay and Western blot analysis.
      Seventy-five patient samples were analyzed by FMIA, ELISA, and Western blotting
      with respect to their immunoreactivity against crude H. pylori extracts and
      individual H. pylori antigens. Statistical analyses revealed an overall
      similarity of more than 90% among the results for FMIA, ELISA, and Western blot.
      Therefore, we conclude that FMIA is a powerful and time- and cost-saving assay
      system for the detection of antimicrobial antibodies, with higher sensitivity and
      a larger measurement range than ELISA.

PMID- 14715560
TI  - Specificity of the antibody response to the pneumococcal polysaccharide and
      conjugate vaccines in human immunodeficiency virus-infected adults.
AB  - Nonspecific antibodies, which are thought to be nonprotective, have been shown to
      contribute a substantial proportion of the measured concentration in the
      standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for
      pneumococcal polysaccharide capsular antibodies. The presence of such antibodies
      in human immunodeficiency virus (HIV)-infected persons has not been evaluated.
      The amount of nonspecific antibodies is proportional to the reduction in IgG
      antibody concentration that occurs with serum absorption with the heterologous
      polysaccharide 22F. We measured the amount of nonspecific antibodies before and
      after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the
      pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4
      counts of >/== 200 cells/mm3. Blood was drawn before and 2 months after
      vaccination. For prevaccination sera, we found a substantial amount of
      nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured
      IgG concentration), but not for serotype 14. There tended to be proportionately
      less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but
      not for PPV. Subjects with a low HIV viral load (</= 400 copies/ml) had
      proportionately more nonspecific antibodies than those with higher viral load
      before and after both vaccines. After 22F absorption, the geometric mean
      concentrations of antibodies were significantly higher post-PCV than post-PPV for
      the high viral load group for all five serotypes, but for no serotypes in the low
      viral load group. These findings confirm that absorption with a heterologous
      pneumococcal polysaccharide (e.g., 22F) is necessary to remove nonspecific
      antibodies in a standardized IgG ELISA for pneumococcal capsular antibodies in
      HIV-infected adults.

PMID- 14715561
TI  - Evaluation of inflammatory and renal-injury markers in women treated with
      antibiotics for acute pyelonephritis caused by Escherichia coli.
AB  - The evolution and the relationship between inflammatory and renal-injury markers
      in women with acute uncomplicated pyelonephritis under antimicrobial therapy were
      investigated in a prospective study. Markers were measured before and 6 and 24 h
      after the intravenous administration of 1 g of ceftriaxone. Before treatment, the
      median levels of all markers except the serum creatinine levels were high. Twenty
      four hours after the onset of antibiotic treatment, the C-reactive protein (CRP)
      level continued to be high, while the serum interleukin-6 (IL-6) levels and the
      urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased
      significantly. In contrast, serum creatinine and tumor necrosis factor alpha
      levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2
      microglobulin levels did not change over time. There was a significant
      correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine
      albumin and IgG levels are glomerular and urinary tract-injury markers) as well
      as between serum CRP levels and the levels of the tubular-injury markers. In
      women with acute pyelonephritis, appropriate antibiotic treatment rapidly
      decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well
      with urine albumin and IgG levels.

PMID- 14715562
TI  - Expression of the bovine leukemia virus envelope glycoprotein (gp51) by
      recombinant baculovirus and its use in an enzyme-linked immunosorbent assay.
AB  - The gene encoding the major envelope glycoprotein (gp51) with its signal
      sequence, represented by an additional NH2-terminal 33-residue amino acid
      sequence of bovine leukemia virus (BLV), was inserted into a baculovirus transfer
      vector. A recombinant virus expressing a secreted gp51 protein in insect cells
      was isolated. The recombinant gp51 expressed was characterized by using an anti
      BLV monoclonal antibody by both Western blotting analysis and enzyme-linked
      immunosorbent assay (ELISA). The secreted gp51 was used as an antigen, and an
      ELISA with recombinant gp51 (rgp51) was developed for the detection of BLV
      antibodies. This new procedure was compared with a previous ELISA method for the
      detection of BLV antibodies and an agar gel immunodiffusion test performed with
      an unpurified BLV antigen preparation. The comparative testing of field samples
      showed that the ELISA with rgp51 is more specific and also suitable for the
      testing of pooled sera.

PMID- 14715563
TI  - Systemic and mucosal responses to oral administration of excretory and secretory
      antigens from Giardia intestinalis.
AB  - Giardia, a flagellated protozoan that infects the upper small intestine of its
      vertebrate host, is the most common parasitic protist responsible for diarrhea
      worldwide. Molecules released by the parasite, particularly excretory and
      secretory antigens, seemed to be associated with pathogenesis as well as with the
      expression of Giardia virulence. In the present work, we examined the effect of
      oral administration of Giardia intestinalis excretory and secretory antigens on
      systemic and local antibody response as well as on mucosal injuries in BALB/c
      mice. Significant titers of serum-specific immunoglobulin G1 (IgG1) and specific
      IgG2a were observed. Systemic and mucosal specific IgA antibodies were also
      recorded. A transient production of serum-specific IgE antibody and high total
      IgE levels were also detected, suggesting the presence in excretory and secretory
      proteins of factors promoting a specific IgE response. The sera of excretory and
      secretory antigen-treated mice recognized proteins of 50 and 58 kDa as well as
      electrophoretic bands of 15, 63, and 72 kDa that could support a proteinase
      activity. The in vitro exposure of G. intestinalis trophozoites to heat
      inactivated sera from mice orally inoculated with excretory and secretory
      antigens induced a decrease of growth, revealing a complement-independent
      inhibitory activity of specific serum antibodies. Furthermore, histological
      evaluation performed on the small and large intestines revealed moderate to acute
      histological changes comparable to those observed in natural or experimental
      Giardia infection characterized by eosinophilic infiltration, hypercellularity,
      and enterocytic desquamation. The present results suggested that Giardia
      excretory and secretory antigens stimulate a preferential Th2 response, which is
      probably involved in the intestinal alterations associated with giardiasis.

PMID- 14715564
TI  - Cytokine production and monocyte HLA-DR expression as predictors of outcome for
      patients with community-acquired severe infections.
AB  - This study was performed to evaluate the impact of pro- and anti-inflammatory
      molecules and human leukocyte antigen DR (HLA-DR) expression as markers of immune
      status for the final outcome of septic patients. The study included 30 patients
      with severe sepsis due to community-acquired infections. Concentrations of tumor
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, IL-10, and
      transforming growth factor beta1 (TGF-beta1) in serum, as well as monocyte HLA-DR
      expression, were determined on admission and on days 3, 10, 13, and 17 during
      hospitalization. Of the 30 patients enrolled, 13 survived, while 17 died during
      their hospital stay. All patients had significantly lower HLA-DR expression and
      higher pro- and anti-inflammatory cytokine levels than healthy individuals. HLA
      DR expression was significantly decreased in nonsurvivors at almost all time
      points. In nonsurvivors, higher levels in serum of TNF-alpha on days 13 and 17;
      IL-6 levels on day 3; and IL-10 on days 3, 10, and 13 were found. Baseline levels
      of TGF-beta1 were significantly higher in survivors. Independent risk factors of
      mortality were IL-10 levels on days 3 and 10, while monocyte HLA-DR expression on
      admission was a good predictor for survival. Several pro- and anti-inflammatory
      cytokines are oversynthesized during severe infections, especially in patients
      with a poor outcome. Monocyte HLA-DR expression is an early and constant
      predictive marker for survival in severe sepsis, while serum IL-10 levels on days
      3 and 10 have negative prognostic value for the final outcome.

PMID- 14715565
TI  - Establishment of adult peripheral blood lymphocyte subset reference range for an
      Asian population by single-platform flow cytometry: influence of age, sex, and
      race and comparison with other published studies.
AB  - We established a normal reference range for peripheral blood lymphocyte subsets
      in a multiracial adult population by using single-platform flow cytometry.
      Further analysis of our cohort showed that the CD8+-cell counts decrease with
      age, there is a gender difference in NK cell percentages and counts, and there
      are significant differences in the CD3+-, CD4+-, and CD19+-cell counts between
      Indians and other racial groups. Overall, our results are significantly different
      from other published data. This difference further stresses the need for
      different populations to establish their own reference ranges as these may have
      important implications for the management of patients with human immunodeficiency
      virus and AIDS. The use of single-platform flow cytometry will eliminate some of
      the variability between different study centers, making studies more comparable.
      This platform should be used for future studies into the effects of age, sex, and
      race on lymphocyte subsets.

PMID- 14715566
TI  - Mastitis increases mammary mRNA abundance of beta-defensin 5, toll-like-receptor
      2 (TLR2), and TLR4 but not TLR9 in cattle.
AB  - Coordination of the primary defense mechanisms against pathogens relies on the
      appropriate expression of pathogen recognition receptors (PRRs) triggering the
      early release of effector molecules of the innate immune system. To analyze the
      impact of this system on the counteraction of infections of the mammary gland
      (mastitis), we characterized the bovine gene encoding the key PRR Toll-like
      receptor 9 (TLR9) and mapped its precise position on chromosome BTA22. The
      sequence information was used to establish real-time PCR quantification assays to
      measure the mRNA abundances of TLR9, TLR2, and TLR4 together with those of beta
      defensin 5 (BNBD5), an early bactericidal effector molecule of the innate system,
      in healthy and infected mammary glands. Mastitis strongly increased (4- to 13
      fold) the mRNA abundances of all of these genes except TLR9. Slight subclinical
      infections already caused a substantial increase in the copy numbers, though they
      did so the least for TLR9. Induction was not systemic, since mRNA abundance was
      low in uninfected control quarters of the udder but high in the severely infected
      quarters of the same animal. The number of TLR2 copies correlated well with those
      of TLR4, indicating coordinated regulation of these two PRRs during infection of
      the udder. Their coordinated regulation explains our unexpected observation that
      pure Staphylococcus aureus infections caused a strong increase also in TLR4 mRNA
      abundance. In situ hybridizations revealed that BNBD5 is expressed predominantly
      in the mammary epithelial cells (MEC) of the infected gland. Our data therefore
      suggest a significant contribution of the innate immune system to counteract
      mastitis and attribute a prominent effector function to the MEC.

PMID- 14715567
TI  - Prevalence of neutralizing antibodies against different rotavirus serotypes in
      children with severe rotavirus-induced diarrhea and their mothers.
AB  - Neutralizing antibody (NAb) responses to different rotavirus serotypes were
      compared in 64 convalescent-phase serum samples from hospitalized rotavirus
      positive children less than 2 years of age and their mothers. Compared to the
      child patients, the mothers showed significantly higher NAb positivity to animal
      rotavirus serotypes G3 simian (96.88%), G6 bovine (85.94%), and G10 bovine
      (25.0%) and to human rotavirus serotypes G8 (79.69%) and G3 (57.81%) (P < 0.01
      for each) but not to human serotypes G1, G2, G4, and G9 (P > 0.05). The overall
      prevalence of NAb among the child patients was low for human rotavirus serotypes
      G1 (20.31%) and G3 (21.8%). The comparative NAb response in individual mother
      child paired serum samples was analyzed against each rotavirus serotype. A
      substantial number of child patients showed higher NAb titers than their mothers
      to serotypes G1, G2, G4, and G9, indicating that these serotypes are the major
      serotypes causing rotavirus diarrhea among the children of Pune, India. In these
      cases, the mothers were either negative or had lower titers of NAbs than their
      children. Correlation was observed between the infecting serotype and child
      patient serum that showed a homologous NAb response at a higher level than that
      of the mother. It appears that when the level of NAb to a particular serotype is
      higher among child patients than among their mothers, that serotype is the
      infecting serotype, and that low titers of NAb among the mothers predispose the
      children to infection with that serotype, if the serotype is in circulation.

PMID- 14715568
TI  - Decreased expression of the CD3zeta chain in T cells infiltrating the synovial
      membrane of patients with osteoarthritis.
AB  - Osteoarthritis (OA) is a heterogeneous disease which rheumatologists consider to
      be noninflammatory. However, recent studies suggest that, at least in certain
      patients, OA is an inflammatory disease and that patients often exhibit
      inflammatory infiltrates in the synovial membranes (SMs) of macrophages and
      activated T cells expressing proinflammatory cytokines. We report here that the
      expression of CD3zeta is significantly decreased in T cells infiltrating the SMs
      of patients with OA. The CD3zeta chain is involved in the T-cell signal
      transduction cascade, which is initiated by the engagement of the T-cell antigen
      receptor and which culminates in T-cell activation. Double immunofluorescence of
      single-cell suspensions derived from the SMs from nine patients with OA revealed
      significantly increased proportions of CD3epsilon-positive (CD3epsilon+) cells
      compared with the proportions of CD3zeta-positive (CD3zeta+) T cells (means +/-
      standard errors of the means, 80.48% +/- 3.92% and 69.02% +/- 6.51%,
      respectively; P = 0.0096), whereas there were no differences in the proportions
      of these cells in peripheral blood mononuclear cells (PBMCs) from healthy donors
      (94.73% +/- 1.39% and 93.79% +/- 1.08%, respectively; not significant). The
      CD3zeta+ cell/CD3epsilon+ cell ratio was also significantly decreased for T cells
      from the SMs of patients with OA compared with that for T cells from the PBMCs of
      healthy donors (0.84 +/- 0.17 and 0.99 +/- 0.01, respectively; P = 0.0302). The
      proportions of CD3epsilon+ CD3zeta+ cells were lower in the SMs of patients with
      OA than in the PBMCs of healthy donors (65.04% +/- 6.7% and 90.81% +/- 1.99%,
      respectively; P = 0.0047). Substantial proportions (about 15%) of CD3epsilon+
      CD3zeta-negative (CD3zeta-) and CD3epsilon-negative (CD3epsilon-) CD3zeta- cells
      were found in the SMs of patients with OA. Amplification of the CD3zeta and
      CD3delta transcripts from the SMs of patients with OA by reverse transcriptase
      PCR consistently exhibited stronger bands for CD3delta cDNA than for CD3zeta cDNA
      The CD3zeta/CD3delta transcript ratio in the SMs of patients with OA was
      significantly lower than that in PBMCs from healthy controls (P < 0.0001). These
      results were confirmed by competitive MIMIC PCR. Immunoreactivities for the
      CD3zeta protein were detected in the SMs of 10 of 19 patients with OA, and they
      were of various intensities, whereas SMs from all patients were CD3epsilon+ (P =
      0.0023). The decreased expression of the CD3zeta transcript and protein in T
      cells from the SMs of patients with OA relative to that of the CD3epsilon
      transcript is suggestive of chronic T-cell stimulation and supports the concept
      of T-cell involvement in OA.

PMID- 14715569
TI  - Induction of nitric oxide production mediated by tumor necrosis factor alpha on
      staphylococcal enterotoxin C-stimulated bovine mammary gland cells.
AB  - Mammary gland (MG) secretions (MGS) derived from secretory cows infected with
      coagulase-negative staphylococci (CoNS) showed somatic cell counts and
      lactoferrin similar to levels found in the MGS of secretory cows infected with
      Staphylococcus aureus. However, nitrite and nitrate (NOx) and staphylococcal
      enterotoxin C (SEC) were found in MGS infected with S. aureus at much higher
      levels than in cows infected with CoNS. These results suggested that NOx could be
      intimately correlated with the production of SEC in secretory cows infected with
      S. aureus. Therefore, we examined the production of NOx and the expression of
      proinflammatory cytokines and microsomal cytochrome P450 (CYP450) after injection
      of SEC into the MGS of secretory cows. We were able to detect NOx and the
      proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) on MG cells of
      SEC-injected MGS. It was also found that CYP450 in the MG cells from SEC-injected
      MGS was down-regulated by approximately one-third in comparison with the cells
      from phosphate-buffered saline-injected MGS. This in vitro system also showed
      that NOx could be induced in the culture of bovine macrophage-lined cells (FBM
      17) with the supernatants of SEC-stimulated bovine peripheral blood lymphocytes
      (BoPBLs) but not in the culture of peripheral mononuclear cells with SEC
      stimulated BoPBLs. The expression of the mRNA for both inducible nitric oxide
      synthase and TNF-alpha in FBM-17 was enhanced by culturing with the supernatant
      of SEC-stimulated BoPBLs, although CYP450 was down-regulated. These results
      indicate that the down-regulation of CYP450 was caused by the production of TNF
      alpha in SEC-stimulating MG cells containing macrophages and via NOx production.
      Therefore, we suggest that NOx released from activated MG cells via the
      superantigenic activity of SEC caused oxidative damage to the MG in S. aureus
      induced mastitis.

PMID- 14715570
TI  - Molecular cloning of a Babesia caballi gene encoding the 134-kilodalton protein
      and evaluation of its diagnostic potential in an enzyme-linked immunosorbent
      assay.
AB  - A Babesia caballi gene encoding the 134-kDa (BC134) protein was immunoscreened
      with B. caballi-infected horse serum. An enzyme-linked immunosorbent assay
      (ELISA) using recombinant BC134 protein could effectively differentiate B.
      caballi-infected horse sera from Babesia equi-infected or noninfected control
      horse sera. These results suggest that the recombinant BC134 protein is a
      potential diagnostic antigen in the detection of B. caballi infection.

PMID- 14715572
TI  - Suitability of frozen serum stored in gel separator primary sampling tubes for
      serological testing.
AB  - The suitability of frozen serum after storage in primary sampling tubes with a
      gel separator for serological enzyme-linked immunosorbent assay testing
      (hepatitis B virus surface antigen [HBs Ag], anti-HBs Ag, anti-Toxoplasma gondii
      immunoglobulin G [IgG], anti-rubella virus IgG, anti-cytomegalovirus IgM, and
      anti-Epstein-Barr virus IgM) was evaluated for 375 samples. No difference was
      found among test results using fresh or stored frozen serum

PMID- 14715571
TI  - Bacterial expression of a human monoclonal antibody-alkaline phosphatase
      conjugate specific for Entamoeba histolytica.
AB  - We previously produced human monoclonal antibody Fab fragments specific to
      Entamoeba histolytica in Escherichia coli. In order to use these Fab fragments
      for diagnostic purposes, an expression vector to produce a fusion protein of Fab
      and alkaline phosphatase (PhoA) in E. coli was designed and constructed. The E.
      coli PhoA gene was fused to the 3' terminus of the gene encoding the heavy-chain
      Fd region. The kappa and Fd genes from a previously prepared antibody clone,
      CP33, which is specific for the 260-kDa lectin of E. histolytica, were used as
      human antibody genes. When the fusion protein of CP33 and PhoA was incubated with
      paraformaldehyde-fixed trophozoites of E. histolytica and developed with a
      substrate, the trophozoites appeared to be stained. These results demonstrate the
      feasibility of bacterial expression of a human monoclonal antibody-PhoA conjugate
      specific for E. histolytica and that the antibody can be used to detect E.
      histolytica antigen without the use of chemically conjugated secondary
      antibodies.

PMID- 14715573
TI  - Recognition of ESAT-6 sequences by antibodies in sera of tuberculous nonhuman
      primates.
AB  - Previous work in our laboratory showed that the ESAT-6 protein of Mycobacterium
      tuberculosis and Mycobacterium bovis induces strong antibody responses in a large
      proportion ( approximately 90%) of experimentally or naturally infected nonhuman
      primates. Here, the antibody response to ESAT-6 in tuberculous monkeys was
      characterized at the epitope level by measuring antibodies to overlapping,
      synthetic peptides spanning the ESAT-6 sequence. The antibody response against
      the COOH-terminal portion of the protein was the strongest in both experimentally
      and naturally infected animals. Moreover, these antibodies became detectable the
      earliest during experimental infection, suggesting an ordered expansion of ESAT-6
      specific B-cell clones in the course of infection. The data support use of
      synthetic peptides in lieu of the full-length ESAT-6 protein in diagnostic
      antibody detection assays.

PMID- 14715574
TI  - Profile of antibodies to the nucleocapsid protein of the severe acute respiratory
      syndrome (SARS)-associated coronavirus in probable SARS patients.
AB  - Profiles of antibodies to the nucleocapsid protein of the severe acute
      respiratory syndrome (SARS)-associated coronavirus in 445 probable SARS patients
      and 3,749 healthy people or non-SARS patients were analyzed by antigen-capturing
      enzyme-linked immunosorbent assay. Antinucleocapsid antibodies were elucidated in
      17.5% of the probable SARS patients 1 to 7 days after the onset of symptoms and
      in 80% of the patients 8 to 14 days after the onset. About 90% of the probable
      SARS patients were positive 15 or more days after illness. Antibody titers
      increased up to 70 days, and high antibody titers were maintained at least for
      another 3 months. Of the healthy people and non-SARS patients, only seven
      (0.187%) were weakly positive.

PMID- 14715575
TI  - Age-related changes in expression of CXCR4 and CCR5 on peripheral blood
      leukocytes from uninfected infants born to human immunodeficiency virus type 1
      infected mothers.
AB  - Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected
      infants revealed high proportions of CXCR4-expressing cells in their cord blood,
      which declined at 4.5 months and increased between 9 and 15 months to levels
      approaching those of uninfected adults. Proportions of CCR5-expressing cells,
      however, were very low in cord blood and subsequently increased with age.

PMID- 14715576
TI  - Treating inguinal hernias.

PMID- 14715577
TI  - Health tourism.

PMID- 14715578
TI  - Preserving today's scientific record for tomorrow.

PMID- 14715579
TI  - Who should look after people with Parkinson's disease?

PMID- 14715580
TI  - Surgery in asymptomatic aortic stenosis.

PMID- 14715581
TI  - WHO confirms SARS in Chinese journalist.

PMID- 14715582
TI  - UK authority sets limit on number of embryos transferred.

PMID- 14715583
TI  - Cold is the main health threat after the Bam earthquake.

PMID- 14715584
TI  - Immunologist accused of misconduct is allowed to relocate.

PMID- 14715586
TI  - US universities review subscriptions to journal "package deals" as costs rise.

PMID- 14715587
TI  - New Zealand moves to ban direct advertising of drugs.

PMID- 14715589
TI  - GMC faces challenge over withdrawing treatment.

PMID- 14715590
TI  - Scottish doctors will have to register financial links to drug companies.

PMID- 14715592
TI  - Hopes that Novartis deal on tuberculosis will spur donations for HIV and malaria.

PMID- 14715595
TI  - India s treatment programme for AIDS is premature.

PMID- 14715596
TI  - Sleeping sickness re-emerges in Uganda.

PMID- 14715597
TI  - Coroner to investigate deaths at Sydney hospitals, as two doctors are suspended.

PMID- 14715598
TI  - Exposure to spouse's smoking increases risk of lung cancer by over 20%.

PMID- 14715599
TI  - Report highlights shortcomings in private medical schools in India.

PMID- 14715600
TI  - German health reform likely to raise costs for patients.

PMID- 14715601
TI  - Tough at the top.

PMID- 14715602
TI  - Cigarette tar yields in relation to mortality from lung cancer in the cancer
      prevention study II prospective cohort, 1982-8.
AB  - OBJECTIVE: To assess the risk of lung cancer in smokers of medium tar filter
      cigarettes compared with smokers of low tar and very low tar filter cigarettes.
      DESIGN: Analysis of the association between the tar rating of the brand of
      cigarette smoked in 1982 and mortality from lung cancer over the next six years.
      Multivariate proportional hazards analyses used to assess hazard ratios, with
      adjustment for age at enrollment, race, educational level, marital status, blue
      collar employment, occupational exposure to asbestos, intake of vegetables,
      citrus fruits, and vitamins, and, in analyses of current and former smokers, for
      age when they started to smoke and number of cigarettes smoked per day. SETTING:
      Cancer prevention study II (CPS-II). PARTICIPANTS: 364 239 men and 576 535 women,
      aged > or = 30 years, who had either never smoked, were former smokers, or were
      currently smoking a specific brand of cigarette when they were enrolled in the
      cancer prevention study. MAIN OUTCOME MEASURE: Death from primary cancer of the
      lung among participants who had never smoked, former smokers, smokers of very low
      tar (< or = 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (> or
      = 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).
      RESULTS: Irrespective of the tar level of their current brand, all current
      smokers had a far greater risk of lung cancer than people who had stopped smoking
      or had never smoked. Compared with smokers of medium tar (15-21 mg) filter
      cigarettes, risk was higher among men and women who smoked high tar (> or = 22
      mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73,
      and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men
      who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02,
      0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen
      for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively). CONCLUSION:
      The increase in lung cancer risk is similar in people who smoke medium tar
      cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes
      (< or = 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings >
      or = 22 mg have an even higher risk of lung cancer.

PMID- 14715603
TI  - Cost effectiveness analysis of intensive versus conventional follow up after
      curative resection for colorectal cancer.
AB  - OBJECTIVE: To determine the cost effectiveness of intensive follow up compared
      with conventional follow up in patients with colorectal cancer. DESIGN:
      Incremental cost effectiveness analysis recognising differences in follow up
      strategies, based on effectiveness data from a meta-analysis of five randomised
      trials. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Taking a health service
      perspective, estimated incremental costs effectiveness ratios for each life year
      gained for five trials and four trials designed for early detection of extramural
      recurrences (targeted surveillance). RESULTS: Based on five year follow up, the
      numbers of life years gained by intensive follow up were 0.73 for the five trial
      model and 0.82 for the four trial model. For the five trials, the adjusted net
      (extra) cost for each patient was 2479 pounds sterling (3550 euros; 4288 dollars)
      and for each life year gained was 3402 pounds sterling, substantially lower than
      the current threshold of NHS cost acceptability (30 000 pounds sterling). The
      corresponding values for the four trial model were 2529 pounds sterling and 3077
      pounds sterling, suggesting that targeted surveillance is more cost effective.
      The main predictor of incremental cost effectiveness ratios was surveillance
      costs rather than treatment costs. Judged against the NHS threshold of cost
      acceptability, the predicted incremental cost threshold was ninefold and the
      effectiveness threshold was 3%. CONCLUSIONS: Based on the available data and
      current costs, intensive follow up after curative resection for colorectal cancer
      is economically justified and should be normal practice. There is a continuing
      need to evaluate the efficacy of specific surveillance tools: this study forms
      the basis for economic evaluations in such trials.

PMID- 14715604
TI  - Recent advances in customising cataract surgery.

PMID- 14715605
TI  - Glaucoma--1: diagnosis.

PMID- 14715606
TI  - Supervised injecting centres.

PMID- 14715607
TI  - Supervised fixing rooms, supervised injectable maintenance clinics--understanding
      the difference.

PMID- 14715608
TI  - Learning from Thailand's health reforms.

PMID- 14715609
TI  - Is the NHS getting better or worse? Role of information in assessing quality is
      undervalued.

PMID- 14715610
TI  - Is the NHS getting better or worse? Better to be vaguely right than precisely
      wrong.

PMID- 14715611
TI  - Is the NHS getting better or worse? Making use of information is the key.

PMID- 14715612
TI  - Is the NHS getting better or worse? Just who gets to choose which data will
      matter?

PMID- 14715613
TI  - Hysterectomy and sexual wellbeing: data were misrepresented.

PMID- 14715614
TI  - Hysterectomy and sexual wellbeing: more questions are yet to be answered.

PMID- 14715615
TI  - Is the NHS getting better or worse? We need to ask the right questions.

PMID- 14715616
TI  - NSAIDs during pregnancy and risk of miscarriage: true risks or only suspicions?

PMID- 14715617
TI  - Different versions of Glasgow coma scale in British hospitals: the 14 point scale
      may be worth defending.

PMID- 14715618
TI  - Danish group reanalyses miscarriage in NSAID users.

PMID- 14715619
TI  - Five Ps in mix of public health advocacy.

PMID- 14715621
TI  - Different versions of Glasgow coma scale in British hospitals: distinction must
      be made between real clinical condition and numbers.

PMID- 14715622
TI  - Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic
      stem cell transplantation reverse the disease phenotype in canine leukocyte
      adhesion deficiency.
AB  - Children with the severe phenotype of the genetic immunodeficiency disease
      leukocyte adhesion deficiency or LAD experience life-threatening bacterial
      infections because of molecular defects in the leukocyte integrin CD18 molecule
      and the resultant failure to express the CD11/CD18 adhesion molecules on the
      leukocyte surface. Hematopoietic stem cell transplantation remains the only
      definitive therapy for LAD; however, the degree of donor chimerism and
      particularly the number of CD18(+) donor-derived neutrophils required to reverse
      the disease phenotype are not known. We performed nonmyeloablative hematopoietic
      stem cell transplantations from healthy matched littermates in 9 dogs with the
      canine form of LAD known as CLAD and demonstrate that in the 3 dogs with the
      lowest level of donor chimerism, less than 500 CD18(+) donor-derived
      neutrophils/microL in the peripheral blood of the CLAD recipients resulted in
      reversal of the CLAD disease phenotype. These results demonstrate the value of a
      disease-specific, large-animal model for identifying the lowest therapeutic level
      required for successful cellular and gene therapy.

PMID- 14715623
TI  - Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier
      in patients with beta thalassemia.
AB  - Although beta thalassemia is considered to be a classic monogenic disease, it is
      clear that there is considerable clinical variability between patients who
      inherit identical beta globin gene mutations, suggesting that there may be a
      variety of genetic determinants influencing different clinical phenotypes. It has
      been suggested that variations in the structure or amounts of a highly expressed
      red cell protein (alpha hemoglobin stabilizing protein [AHSP]), which can
      stabilize free alpha globin chains in vitro, could influence disease severity in
      patients with beta thalassemia. To address this hypothesis, we studied 120
      patients with Hb E-beta thalassemia with mild, moderate, or severe clinical
      phenotypes. Using gene mapping, direct genomic sequencing, and extended haplotype
      analysis, we found no mutation or specific association between haplotypes of AHSP
      and disease severity in these patients, suggesting that AHSP is not a disease
      modifier in Hb E-beta thalassemia. It remains to be seen if any association
      between AHSP and clinical severity is present in other population groups with a
      high frequency of beta thalassemia.

PMID- 14715624
TI  - Inhibition of fibroblast growth factor receptor 3 induces differentiation and
      apoptosis in t(4;14) myeloma.
AB  - We have previously shown that dysregulation of fibroblast growth factor receptor
      3 (FGFR3) by the t(4;14) translocation is a primary event in multiple myeloma
      (MM) and that activating mutations of FGFR3 are acquired in some cases. We
      describe here inhibition of wild-type (WT) and constitutively activated mutant
      FGFR3 autophosphorylation by the small molecule inhibitor, PD173074. Inhibition
      of FGFR3 in human myeloma cell lines was associated with decreased viability and
      tumor cell growth arrest. Further, morphologic, phenotypic, and functional
      changes typical of plasma cell (PC) differentiation, including increase in light
      chain secretion and expression of CD31, were observed and this was followed by
      apoptosis. Finally, using a mouse model of FGFR3 myeloma, we demonstrate a delay
      in tumor progression and prolonged survival of mice treated with PD173074. These
      results indicate that inhibition of FGFR3, even in advanced disease associated
      with multiple genetic changes, may allow the cell to complete its developmental
      program and render it sensitive to apoptotic signals. In addition, this
      represents the validation of a therapeutic target in MM that may benefit patients
      who have a very poor prognosis with currently available treatments.

PMID- 14715625
TI  - Circulating endothelial cells as a marker of endothelial damage in allogeneic
      hematopoietic stem cell transplantation.
AB  - Damage to endothelial cells is the common feature of vascular disorders
      associated with hematopoietic stem cell transplantation (HSCT). Elevated numbers
      of circulating endothelial cells reflect the extent of endothelial damage in a
      variety of disorders but their use in HSCT has not been investigated so far. We
      studied 39 patients undergoing allogeneic HSCT with different conditioning
      regimens and 22 healthy controls. Circulating endothelial cells were enumerated
      with immunomagnetic isolation during the course of HSCT. After conditioning, cell
      numbers were significantly elevated (median 44 cells/mL) compared with baseline
      (median 16 cells/mL) and controls (median 8 cells/mL). Patients who received
      radiation had an earlier peak when compared with patients who received
      chemotherapy. Patients who received reduced-intensity conditioning had
      significantly lower cell numbers (median 24 cells/mL) than those who received
      standard conditioning. These observations provide a novel marker to investigate
      microvascular endothelial damage and the effects of different conditioning
      regimens in patients undergoing HSCT.

PMID- 14715628
TI  - Transcriptional profiling of IKK2/NF-kappa B- and p38 MAP kinase-dependent gene
      expression in TNF-alpha-stimulated primary human endothelial cells.
AB  - Inflammatory stimulation of endothelial cells by tumor necrosis factor alpha (TNF
      alpha) involves activation of nuclear factor kappa B (NF-kappa B) and p38 mitogen
      activated protein (MAP) kinase signaling pathways. A reliable analysis of the
      gene expression program elicited by TNF-alpha and its assignment to distinct
      signaling pathways is not available. A sophisticated analysis of oligonucleotide
      microarrays covering more than 13 000 genes allowed definition of the TNF-alpha
      regulated endothelial gene expression profile and novel TNF-alpha-induced genes.
      Virtually all TNF-alpha-inducible genes were dependent on I kappa B kinase 2
      (IKK2)/NF-kappa B activation, whereas a minor number was additionally modulated
      by p38. Furthermore, genes suppressed by IKK2/NF-kappa B were newly identified.
      Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and flow
      cytometry confirmed reliability of data. Thus, these results define a list of
      primary candidates for targeted modulation of endothelial functions during
      inflammation.

PMID- 14715629
TI  - Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the
      phosphatidylserine receptor.
AB  - Clearance of apoptotic cells by macrophages is considered important for
      prevention of inflammatory responses leading to tissue damage. The
      phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine
      (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic
      cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue
      was addressed by generating PSR-deficient (PSR(-/-)) mice. PSR(-/-) mice
      exhibited severe anemia and died during the perinatal period. In the PSR(-/-)
      fetal livers, erythroid differentiation was blocked at an early erythroblast
      stage. In addition, PSR(-/-) embryos exhibited thymus atrophy owing to a
      developmental defect of T-lymphoid cells. Clearance of apoptotic cells by
      macrophages was impaired in both liver and thymus of PSR(-/-) embryos. However,
      this did not induce up-regulation of inflammatory cytokines. These results
      indicate that during embryonic development, PSR-mediated apoptotic cell uptake is
      required for definitive erythropoiesis and T lymphopoiesis, independently of the
      prevention of inflammatory responses.

PMID- 14715630
TI  - Imatinib and plasmacytoid dendritic cell function in patients with chronic
      myeloid leukemia.
AB  - Plasmacytoid dendritic cells (PDCs) are crucial effectors in innate immunity. In
      this study, we show that imatinib, a potent inhibitor of BCR/ABL tyrosine kinase
      activity, in the presence of Flt3-Ligand, could induce CD34+ progenitors from
      chronic myeloid leukemia (CML) to give rise in vitro to typical BDCA-2+ type I
      interferon-producing PDCs. The effect of imatinib on PDC generation was related
      to up-regulation of Flt3 on leukemic CD34+ progenitors. Moreover, patients with
      chronic myeloid leukemia (CML) who were in complete cytogenetic or molecular
      response after imatinib treatment restored their blood PDCs both quantitatively
      and functionally comparable to healthy donors, in contrast to patients not
      responding to imatinib, further confirming that disease response to imatinib is
      accompanied by restoration of PDC function in vivo. These findings provide
      evidence that response to imatinib is capable to restore some DC-related immune
      functions in CML that might be beneficial for long-term disease control.

PMID- 14715632
TI  - In vivo imaging of graft-versus-host-disease in mice.
AB  - We have developed a mouse system by which to track the migration and homing of
      cells in a setting of bone marrow transplantation (BMT)-induced graft-versus-host
      disease (GVHD) after systemic infusion using enhanced green fluorescence protein
      (eGFP) transgenic (Tg) cells and a simple application of a fluorescence
      stereomicroscope outfitted with a color charge-coupled device (CCD) camera. Whole
      body images of anesthetized mice taken at various time points after cell infusion
      revealed the early migration of allogeneic cells to peripheral lymphoid organs,
      with later infiltration of GVHD target organs. Localization of eGFP Tg cells
      could be seen through the skin of shaved mice, and internal organs were easily
      discernible. After allogeneic or syngeneic eGFP Tg cell infusion, representative
      mice were dissected to better visualize deeper internal organs and tissues.
      Infusion of different cell populations revealed distinct homing patterns, and
      this method also provided a simple way to identify the critical time points for
      expansion of the transplanted cells in various organs. This simple application of
      the fluorescence stereomicroscope will be valuable for GVHD and graft-versus
      tumor studies in which visualization of cellular migration, expansion, and cell
      cell interactions will be more informative when analyzed by such an intravital
      method.

PMID- 14715636
TI  - Light-chain only multiple myeloma is due to the absence of functional
      (productive) rearrangement of the IgH gene at the DNA level.
AB  - Although most multiple myeloma (MM) cases are characterized by the detection of a
      monoclonal immunoglobulin in the serum, about 15% of the patients present only
      immunoglobulin light chains, detected either in the urine or serum or both. These
      patients are designated as having light-chain (LC) MM. Using fiber-fluorescent in
      situ hybridization, and in contrast to patients and myeloma cell lines secreting
      heavy chains (who presented a legitimate functional IgH rearrangement in every
      case), LC MM never displayed a functional IgH recombination. Interestingly, most
      LC MM cases presented one IgH allele with a germline configuration (including the
      DJ region), the second allele being usually involved in an illegitimate
      recombination. Of note, most of these translocations occurred close to (or at)
      switch regions, even though in some cases, breakpoints involving nonswitch
      regions were observed. Thus, this study clearly showed that LC MM is due to the
      absence of legitimate IgH rearrangement at the DNA level, reflecting possible
      abnormalities in the IgH gene recombinations during B-cell maturation.
      Furthermore, it showed that this defect did not prevent the activation of the
      switch process because most of 14q32 translocations observed in LC MM occurred at
      switch regions.

PMID- 14715639
TI  - CD45-associated protein inhibits CD45 dimerization and up-regulates its protein
      tyrosine phosphatase activity.
AB  - CD45, a receptor-like protein tyrosine phosphatase (PTP), plays an essential role
      in lymphocyte development and immune responses. Recent evidence suggests that
      dimerization of CD45 down-regulates its function. However, the mechanisms by
      which CD45 dimerization is regulated remain unclear, and there is no direct
      evidence that the PTP activity of CD45 dimers is less than that of monomers. CD45
      in lymphocytes associates with CD45-AP (CD45-associated protein). Here we show
      that T cells from CD45-AP-null mice have a much higher level of CD45 dimers than
      those of wild-type mice, suggesting that CD45-AP inhibits CD45 dimer formation.
      This was confirmed with the use of a novel CD45-AP-null T-cell line, ALST-1, that
      we established from a spontaneous thymic tumor found in a CD45-AP-null mouse.
      Transfected CD45-AP inhibited CD45 dimer formation in ALST-1 cells in proportion
      to the amount of CD45-AP expressed. Finally, with the use of microsomal fractions
      from both mouse thymocytes and ALST-1 transfectants, the PTP activity of CD45 was
      found to be significantly lower in CD45-AP-negative cells than in CD45-AP
      positive cells. Therefore, our results support a model in which binding of CD45
      AP to inactive CD45 dimers converts them to active monomers.

PMID- 14715640
TI  - Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1
      during human erythropoiesis.
AB  - The transcription factor TAL1 has major functions during embryonic hematopoiesis
      and in adult erythropoiesis and megakaryocytopoiesis. These functions rely on
      different TAL1 structural domains that are responsible for dimerization,
      transactivation, and DNA binding. Previous work, most often done in mice, has
      shown that some TAL1 functions do not require DNA binding. To study the role of
      TAL1 and the relevance of the TAL1 DNA-binding domain in human erythropoiesis, we
      developed an approach that allows an efficient enforced wild-type or mutant TAL1
      protein expression in human hematopoietic CD34(+) cells using a lentiviral
      vector. Differentiation capacities of the transduced cells were studied in a
      culture system that distinguishes early and late erythroid development. Results
      indicate that enforced TAL1 expression enhances long-term culture initiating cell
      (LTC-IC) potential and erythroid differentiation of human CD34(+) cells as shown
      by increased beta globin and porphobilinogen deaminase (PBGD) gene expressions
      and erythroid colony-forming units (CFU-Es), erythroid burst-forming units (BFU
      Es), and glycophorin A-positive (GPA(+)) cell productions. Enforced expression of
      a TAL1 protein deleted of its DNA-binding domain (named Delta bTAL1) mimicked
      most TAL1 effects except for the LTC-IC enhancement, the down-regulation of the
      CD34 surface marker, and the GPA(+) cell production. These results provide the
      first functional indications of DNA-binding-dependent and -independent roles of
      TAL1 in human erythropoiesis.

PMID- 14715641
TI  - Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into
      the NOD/SCID mouse and their role in supporting human CD34 cell engraftment.
AB  - The Stro-1 antigen potentially defines a mesenchymal stem cell (MSC) progenitor
      subset. We here report on the role of human ex vivo-expanded selected Stro-1(+)
      or Stro-1(-) MSC subsets on the engraftment of human CD34(+) cord blood cells in
      the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model.
      The data show that cotransplantation of expanded Stro-1(-) cells with CD34(+)
      cells resulted in a significant increase of human CD45, CD34, CD19, and CD11b
      cells detected in blood or in bone marrow (BM) and spleen as compared with the
      infusion of CD34(+) cells alone. Infusion into mice of expanded Stro-1(+) and
      Stro-1(-) cells (without CD34(+) cells) showed that the numbers of Stro-1(+)
      derived (as assessed by DNA analysis of human beta-globin with quantitative
      polymerase chain reaction [PCR]) were higher than Stro-1(-)-derived cells in
      spleen, muscles, BM, and kidneys, while more Stro-1(-)-derived than Stro-1(+)
      derived cells were found in lungs. The transduction of expanded Stro-1(+) cells
      with an enhanced green fluorescent protein (eGFP) gene did not modify their
      cytokine release and their homing in NOD/SCID mouse tissues. The difference
      between the hematopoietic support and the homing capabilities of expanded Stro
      1(+) and Stro-1(-) cells may be of importance for clinical therapeutic
      applications: Stro-1(+) cells may rather be used for gene delivery in tissues
      while Stro-1(-) cells may rather be used to support hematopoietic engraftment.

PMID- 14715642
TI  - Genetic testing for cardiovascular disease susceptibility: a useful clinical
      management tool or possible misinformation?
AB  - Genetic susceptibility tests are already advertised on the Internet to identify
      individuals at above average risk for cardiovascular disease (CVD), such as deep
      vein thrombosis, hyperlipidemia, or atherosclerosis, whereas other tests claim to
      predict response to a particular drug treatment. Some kits are available to the
      public directly, bypassing a doctor. Their value, however, must be considered
      carefully, because although a genotype may be strongly and consistently
      associated with an intermediate trait, and because the intermediate trait is a
      strong predictor of CVD risk, there may be little or no association of genotype
      with risk over and above that of the measured trait. This is because multigenic
      effects and environmental modification (context dependency) of genotype effects
      determine CVD risk. An individual's personal characteristics and plasma risk
      trait levels (which reflect both genotype and exposure) at present are the best
      predictors of clinical outcome. Only when genetic tests surpass this, possibly by
      the inclusion of many functional common variants, in conjunction with their
      context-dependent effects on risk, might their usefulness in clinical management
      be realized. Here we review some of the particular issues and concerns raised by
      CVD-risk genetic testing, and suggest areas of further research to address these
      issues.

PMID- 14715643
TI  - Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal
      models.
AB  - Epidemiological studies in humans, as well as experimental studies in animal
      models, have shown an association between visceral obesity and dyslipidemia,
      insulin resistance, and type 2 diabetes mellitus. Recently, attention has been
      focused on the excessive accumulation of triglycerides (TG) in the liver as part
      of this syndrome. In this review, important principles of the pathophysiological
      involvement of the liver in the metabolic syndrome obtained in rodent models are
      summarized. We focus on non-alcoholic causes of steatosis, because the animal
      experiments we refer to did not include alcohol as an experimental condition. In
      general, there is continuous cycling and redistribution of non-oxidized fatty
      acids between different organs. The amount of TG in an intrinsically normal liver
      is not fixed but can readily be increased by nutritional, metabolic, and
      endocrine interactions involving TG/free fatty acid (FFA) partitioning and TG/FFA
      metabolism. Several lines of evidence indicate that hepatic TG accumulation is
      also a causative factor involved in hepatic insulin resistance. Complex
      interactions between endocrine, metabolic, and transcriptional pathways are
      involved in TG-induced hepatic insulin resistance. Therefore, the liver
      participates passively and actively in the metabolic derangements of the
      metabolic syndrome. We speculate that similar mechanisms may also be involved in
      human pathophysiology.

PMID- 14715645
TI  - Mechanical stretch induces phosphorylation of p38-MAPK and apoptosis in human
      saphenous vein.
AB  - OBJECTIVE: Failure of saphenous vein grafts remains a major limitation of
      coronary bypass surgery. The aims of the present study were to determine whether
      pressure distension of human saphenous vein induces the activation of p38-MAPK
      and to determine its role in apoptosis. METHODS AND RESULTS: Phosphorylated p38
      was detected at basal levels in human saphenous vein obtained immediately after
      harvesting. Distended saphenous vein showed significantly higher levels of
      phosphorylated p38 compared with control vein (P<0.01) and nondistended saphenous
      vein maintained for 3 and 6 hours after harvesting (both P<0.01). Apoptosis in
      distended and nondistended vein was significantly higher at 24 hours compared
      with control vein, with distended vein showing increased apoptosis compared with
      nondistended saphenous vein at all time points investigated (P<0.001).
      Immunolocalization showed co-localization of phosphorylated p38 and apoptosis.
      Inhibition of p38 activity reduced the apoptotic index of cultured vascular
      smooth muscle cells by 72.1%+/-1.2% and cultured distended saphenous vein
      segments by 72.7%+/-0.9%. CONCLUSIONS: Pressure distension of intact human
      saphenous vein induces activation of p38, and this is associated with apoptosis.
      Inhibition of p38 kinase activity in saphenous vein smooth muscle cells and
      intact vein reduces apoptosis. These findings contribute to our understanding of
      the mechanisms of saphenous vein graft failure.

PMID- 14715644
TI  - Membrane-potential-dependent inhibition of platelet adhesion to endothelial cells
      by epoxyeicosatrienoic acids.
AB  - OBJECTIVE: Epoxyeicosatrienoic acids (EETs) are potent vasodilators produced by
      endothelial cells. In many vessels, they are an endothelium-derived
      hyperpolarizing factor (EDHF). However, it is unknown whether they act as an EDHF
      on platelets and whether this has functional consequences. METHODS AND RESULTS:
      Flow cytometric measurement of platelet membrane potential using the fluorescent
      dye DiBac4 showed a resting potential of -58+/-9 mV. Different EET regioisomers
      hyperpolarized platelets down to -69+/-2 mV, which was prevented by the non
      specific potassium channel inhibitor charybdotoxin and by use of a blocker of
      calcium-activated potassium channels of large conductance (BK(Ca) channels),
      iberiotoxin. EETs inhibited platelet adhesion to endothelial cells under static
      and flow conditions. Exposure to EETs inhibited platelet P-selectin expression in
      response to ADP. Stable overexpression of cytochrome P450 2C9 in EA.hy926 cells
      (EA.hy2C9 cells) resulted in release of EETs and a factor that hyperpolarized
      platelets and inhibited their adhesion to endothelial cells. These effects were
      again inhibited by charybdotoxin and iberiotoxin. CONCLUSIONS: EETs hyperpolarize
      platelets and inactivate them by inhibiting adhesion molecule expression and
      platelet adhesion to cultured endothelial cells in a membrane potential-dependent
      manner. They act as an EDHF on platelets and might be important mediators of the
      anti-adhesive properties of vascular endothelium.

PMID- 14715646
TI  - Birth weight and lipids in a national birth cohort study.
AB  - OBJECTIVE: To investigate the association between birth weight and lipid levels
      in a 53-year-old birth cohort from England, Scotland, and Wales. METHODS AND
      RESULTS: Lipid levels were obtained from nonfasting blood samples, collected at
      the most recent follow-up of the MRC National Survey of Health and Development,
      for 2559 men and women. Regression models indicated that in men, a 1-kg increase
      in birth weight was associated with a 0.13-mmol/L decrease (95% CI: -0.23, -0.01)
      in total cholesterol at age 53 years (P=0.03), compared with a 0.02-mmol/L (95%
      CI: -0.11, 0.15) increase in women and a 0.06-mmol/L (95% CI: -0.15, 0.02)
      decrease in men and women combined. Adjustment for current height and body mass
      index (BMI) in men reduced the size of the relationship, with height being
      responsible for the reduction. Adult height and height at 2 and 4 years were
      significantly associated with total cholesterol in men and in men and women
      combined. The negative association between total cholesterol and birth weight was
      strongest among men with high BMI at age 53 years (P=0.03 for test for
      interaction between birth weight and BMI). There was no significant association
      between birth weight and LDL or HDL cholesterol in men or women before
      adjustment, but there was a positive association with HDL in women. When both
      sexes were analyzed together, an association was seen after adjustment for
      current body size. No confounding of these findings with social class was
      observed in this study. CONCLUSIONS: Our results suggest that the small effect of
      birth weight on lipid levels at age 53 years has a limited public health impact.
      The findings suggest that childhood height growth may be more important than
      prenatal growth.

PMID- 14715648
TI  - Inhibitory mechanism of store-operated Ca2+ channels by zinc.
AB  - Capacitative calcium influx plays an important role in shaping the Ca(2+)
      response of various tissues and cell types. Inhibition by heavy metals is a
      hallmark of store-operated calcium channel (SOCC) activity. Paradoxically,
      although zinc is the only potentially physiological relevant ion, it is the least
      investigated in terms of inhibitory mechanism. In the present study, we
      characterize the inhibitory mechanism of the SOCC by Zn(2+) in the human salivary
      cell line, HSY, and rat salivary submandibular ducts and acini by monitoring SOCC
      activity using fluorescence imaging. Analysis of Zn(2+) inhibition indicated that
      Zn(2+) acts as a competitive inhibitor of Ca(2+) influx but does not permeate
      through the SOCC, suggesting that Zn(2+) interacts with an extracellular site of
      SOCC. Application of the reducing agents, dithiothreitol (DTT) and beta
      mercaptoethanol, totally eliminated Zn(2+) and Cd(2+) inhibition of SOCC,
      suggesting that cysteines are part of the Zn(2+) and Cd(2+) binding site.
      Interestingly, reducing conditions failed to eliminate the inhibition of SOCC by
      La(3+) and Gd(3+), indicating that the Zn(2+) and lanthanides binding sites are
      distinct. Finally, we show that changes in redox potential and Zn(2+) are
      regulating, via SOCC activity, the agonist-induced Ca(2+) response in salivary
      ducts. The presence of a specific Zn(2+) site, responsive to physiological Zn(2+)
      and redox potential, may not only be instrumental for future structural studies
      of various SOCC candidates but may also reveal novel physiological aspects of the
      interaction between zinc, redox potential, and cellular Ca(2+) homeostasis.

PMID- 14715649
TI  - Transient phosphatidylinositol 3-kinase inhibition protects immature primary
      cortical neurons from oxidative toxicity via suppression of extracellular signal
      regulated kinase activation.
AB  - Oxidative stress has been shown to underlie a diverse range of neuropathological
      conditions. Glutamate-induced oxidative toxicity is a well described model of
      oxidative stress-induced neurodegeneration that relies upon the ability of
      extracellular glutamate to inhibit a glutamate/cystine antiporter, which results
      in a depletion of intracellular cysteine and the blockade of continued
      glutathione synthesis. Glutathione depletion leads to a gradual toxic
      accumulation of reactive oxygen species. We have previously determined that
      glutamate-induced oxidative toxicity is accompanied by a robust increase in
      activation of the mitogen-activated protein kinase (MAPK) member extracellular
      signal regulated kinase (ERK) and that this activation is essential for neuronal
      cell death. This study demonstrates that delayed ERK activation is dependent upon
      the activity of phosphoinositol-3 kinase (PI3K) and that transient but not
      sustained PI3K inhibition leads to significant protection of neurons from
      oxidative stress-induced neurodegeneration. Furthermore, we show that transient
      PI3K inhibition prevents the delayed activation of MEK-1, a direct activator of
      ERK, during oxidative stress. Thus, this study is the first to demonstrate a
      novel level of cross-talk between the PI3K and ERK pathways in cultured immature
      cortical neuronal cultures that contributes to the unfolding of a cell death
      program. The PI3K pathway, therefore, may serve opposing roles during the
      progression of oxidative stress in neurons, acting at distinct kinetic phases to
      either promote or limit a slowly developing program of cell death.

PMID- 14715650
TI  - Loose protein packing around the extracellular half of the GABA(A) receptor beta1
      subunit M2 channel-lining segment.
AB  - GABA(A) receptors are ligand-gated ion channels formed by the pseudosymmetrical
      assembly of five homologous subunits around the central channel axis. The five M2
      membrane-spanning segments largely line the channel. In the present work we
      probed the water surface accessibility of the beta(1) subunit M2 segment using
      the substituted cysteine accessibility method. We assayed the reaction of the
      negatively charged sulfhydryl-specific reagent, p-chloromercuribenzenesulfonate
      (pCMBS(-)), by its effect on subsequent currents elicited by EC(50) and
      saturating GABA concentrations. pCMBS(-), applied with GABA, reacted with 14 of
      the 19 residues tested. At the M2 cytoplasmic end from 2' to 6' only beta(1)A252C
      (2') and beta(1)T256C (6') were pCMBS(-)-reactive in the presence of GABA. We
      infer that the M2 segments are tightly packed in this region. Toward the
      extracellular half of M2 all residues from beta(1)T262C (12') through
      beta(1)E270C (20') reacted with pCMBS(-) applied with GABA. We infer that this
      region is highly mobile and loosely packed against the rest of the protein. Based
      on differences in pCMBS(-) reaction rates two domains can be distinguished on the
      putative channel-lining side of M2. A faster reacting domain includes the 2', 9',
      12', 13', and 16' residues. The slower reacting face contains the 6', 10', and
      14' residues. We hypothesize that these may represent the channel-lining faces in
      the closed and open states and that gating involves an 80-100 degrees rotation of
      the M2 segments. These results are consistent with the loose packing of the M2
      segments inferred from the structure of the homologous Torpedo nicotinic
      acetylcholine receptor.

PMID- 14715651
TI  - Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the
      catalytic mechanism and the molecular basis for fucosidosis.
AB  - Fucosylated glycoconjugates are involved in numerous biological events, and alpha
      l-fucosidases, the enzymes responsible for their processing, are therefore of
      crucial importance. Deficiency in alpha-l-fucosidase activity is associated with
      fucosidosis, a lysosomal storage disorder characterized by rapid
      neurodegeneration, resulting in severe mental and motor deterioration. To gain
      insight into alpha-l-fucosidase function at the molecular level, we have
      determined the crystal structure of Thermotoga maritima alpha-l-fucosidase. This
      enzyme assembles as a hexamer and displays a two-domain fold, composed of a
      catalytic (beta/alpha)(8)-like domain and a C-terminal beta-sandwich domain. The
      structures of an enzyme-product complex and of a covalent glycosyl-enzyme
      intermediate, coupled with kinetic and mutagenesis studies, allowed us to
      identify the catalytic nucleophile, Asp(244), and the Bronsted acid/base,
      Glu(266). Because T. maritima alpha-l-fucosidase occupies a unique evolutionary
      position, being far more closely related to the mammalian enzymes than to any
      other prokaryotic homolog, a structural model of the human enzyme was built to
      document the structural consequences of the genetic mutations associated with
      fucosidosis.

PMID- 14715652
TI  - Functional characterization of pendrin in a polarized cell system. Evidence for
      pendrin-mediated apical iodide efflux.
AB  - Pendred's syndrome is an autosomal recessive disorder characterized by
      sensorineural deafness, goiter, and impaired iodide organification. It is caused
      by mutations in the PDS/SLC26A4 gene that encodes pendrin. Functionally, pendrin
      is a transporter of chloride and iodide in Xenopus oocytes and heterologous
      mammalian cells and a chloride/base exchanger in beta-intercalated cells of the
      renal cortical collecting duct. The partially impaired thyroidal iodide
      organification in Pendred's syndrome suggests a possible role of pendrin in
      iodide transport at the apical membrane of thyroid follicular cells, but
      experimental evidence for this concept is lacking. The iodide transport
      properties of pendrin were determined in polarized Madin-Darby canine kidney
      cells expressing the sodium iodide symporter (NIS), pendrin, or NIS and pendrin
      using a bicameral system-permitting measurement of iodide content in the basal,
      intracellular, and apical compartments. Moreover, we determined the functional
      consequences of two naturally occurring mutations (L676Q and FS306>309X). In
      polarized Madin-Darby canine kidney cells, NIS mediates uptake at the basolateral
      membrane. Only minimal amounts of iodide reach the apical compartment in the
      absence of pendrin. In cells expressing NIS and pendrin, pendrin mediates
      transport of iodide into the apical chamber. Wild type pendrin also mediates
      iodide efflux in transiently transfected cells. In contrast, both pendrin mutants
      lose the ability to promote iodide efflux. These results provide evidence that
      pendrin mediates apical iodide efflux from polarized mammalian cells loaded with
      iodide. Consistent with the partial organification defect observed in patients
      with Pendred's syndrome, naturally occurring mutations of pendrin lead to
      impaired transport of iodide.

PMID- 14715653
TI  - The glucose-regulated nuclear localization of hexokinase 2 in Saccharomyces
      cerevisiae is Mig1-dependent.
AB  - Two major mediators of glucose repression in Saccharomyces cerevisiae are the
      proteins Mig1 and Hxk2. The mechanism of Hxk2-dependent glucose repression
      pathway is not well understood, but the Mig1-dependent part of the pathway has
      been elucidated in great detail. Here we report that Hxk2 has a glucose-regulated
      nuclear localization and that Mig1, a transcriptional repressor responsible for
      glucose repression of many genes, is required to sequester Hxk2 into the nucleus.
      Mig1 and Hxk2 interacted in vivo in a yeast two-hybrid assay and in vitro in
      immunoprecipitation and glutathione S-transferase pull-down experiments. We found
      that the Lys(6)-Met(15) decapeptide of Hxk2, which is necessary for nuclear
      localization of the protein, is also essential for interaction with the Mig1
      protein. Our results also show that the Hxk2-Mig1 interaction is of physiological
      significance because both proteins have been found interacting together in a
      cluster with DNA fragments containing the MIG1 site of SUC2 promoter. We conclude
      that Hxk2 operates by interacting with Mig1 to generate a repressor complex
      located in the nucleus of S. cerevisiae during growth in glucose medium.

PMID- 14715654
TI  - Activated thrombin-activatable fibrinolysis inhibitor reduces the ability of high
      molecular weight fibrin degradation products to protect plasmin from antiplasmin.
AB  - Activated thrombin-activable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase
      B-like plasma enzyme that can slow clot lysis by removing lysine residues exposed
      on fibrin as it is cleaved by plasmin. Previously, it was shown that fibrin
      treated with TAFIa is less able to promote plasminogen activation by tissue-type
      plasminogen activator. In this study, the effect of TAFIa modification of a
      fibrin surface on the rate of plasmin inhibition by antiplasmin was studied using
      high molecular weight fibrin degradation products (HMw-FDPs) as a soluble model
      for intact plasmin-modified fibrin. To quantify the inhibition, a novel end point
      assay was employed where plasmin, antiplasmin, and cofactors were mixed in the
      presence of a chromogenic substrate and the end point in the substrate hydrolysis
      reaction was used to measure the second order rate constant of inhibition. When
      HMw-FDPs were titrated in the presence of plasmin and antiplasmin, the rate
      constant for inhibition decreased by 16-fold at saturation (9.6 x 10(6) m(-1) s(
      1) to 0.59 x 10(6) m(-1) s(-1)). When HMw-FDPs were pretreated with TAFIa, nearly
      two-thirds of the protective effect was lost. When 730 nm HMw-FDPs were treated
      for 20 min with TAFIa, the rate constant for plasmin inhibition was increased 3
      fold from 1.9 x 10(6) m(-1) s(-1) to 6.2 x 10(6) m(-1) s(-1). Therefore, a novel
      mechanism was identified whereby TAFIa can modulate plasmin levels by increasing
      the susceptibility of plasmin to inhibition by antiplasmin.

PMID- 14715655
TI  - A study of the protection of plasmin from antiplasmin inhibition within an intact
      fibrin clot during the course of clot lysis.
AB  - Previous work using soluble fibrin surrogates or very dilute fibrin indicate that
      inhibition of plasmin by antiplasmin is attenuated by fibrin surrogates; however,
      this phenomenon has not been quantified within intact fibrin clots. Therefore, a
      novel system was designed to measure plasmin inhibition by antiplasmin in real
      time within an intact clot during fibrinolysis. This was accomplished by
      including the plasmin substrate S2251 and a recombinant fluorescent derivative of
      plasminogen (S741C-fluorescein) into clots formed from purified components.
      Steady state plasmin levels were estimated from the rates of S2251 hydrolysis,
      the rates of plasminogen activation were estimated by fluorescence decrease over
      time, and residual antiplasmin was deduced from residual fluorescence. From these
      measurements, the second order rate constant could be inferred at any time during
      fibrinolysis. Immediately after clot formation, the rate constant for inhibition
      decreased 3-fold from 9.6 x 10(6) m(-1) s(-1) measured in a soluble buffer system
      to 3.2 x 10(6) m(-1) s(-1) in an intact fibrin clot. As the clot continued to
      lyse, the rate constant for inhibition continued to decrease by 38-fold at
      maximum. To determine whether this protection was the result of plasmin exposure
      of carboxyl-terminal lysine residues, clots were formed in the presence of
      activated thrombin-activatable fibrinolysis inhibitor (TAFIa). In the presence of
      TAFIa, the initial protective effect associated with clot formation occurred;
      however, the secondary protective effect associated with lysine residue exposure
      was delayed in a TAFIa concentration-dependent manner. This latter effect
      represents another mechanism whereby TAFIa attenuates fibrinolysis.

PMID- 14715656
TI  - Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and
      represents an endogenous inhibitor of these enzymes.
AB  - Osteoarthritis is characterized by the loss of aggrecan and collagen from the
      cartilage extracellular matrix. The proteinases responsible for the breakdown of
      cartilage aggrecan include ADAMTS-4 (aggrecanase 1) and ADAMTS-5 (aggrecanase 2).
      Post-translational inhibition of ADAMTS-4/-5 activity may be important for
      maintaining normal homeostasis of aggrecan metabolism, and thus, any disruption
      to this inhibition could lead to accelerated aggrecan breakdown. To date TIMP-3
      (tissue inhibitor of matrix metalloproteinases-3) is the only endogenous
      inhibitor of ADAMTS-4/-5 that has been identified. In the present studies we
      identify alpha(2)-macroglobulin (alpha(2)M) as an additional endogenous inhibitor
      of ADAMTS-4 and ADAMTS-5. alpha(2)M inhibited the activity of both ADAMTS-4 and
      ADAMTS-5 in a concentration-dependent manner, demonstrating 1:1 stoichiometry
      with second-order rate constants on the order of 10(6) and 10(5) m(-1) s(-1),
      respectively. Inhibition of the aggrecanases was mediated by proteolysis of the
      bait region within alpha(2)M, resulting in physical entrapment of these
      proteinases. Both ADAMTS-4 and ADAMTS-5 cleaved alpha(2)M at Met(690)/Gly(691),
      representing a novel proteinase cleavage site within alpha(2)M and a novel site
      of cleavage for ADAMTS-4 and ADAMTS-5. Finally, the use of the anti-neoepitope
      antibodies to detect aggrecanase-generated alpha(2)M-fragments in synovial fluid
      was investigated and found to be uninformative.

PMID- 14715657
TI  - Camptothecin-sensitive relaxation of supercoiled DNA by the topoisomerase I-like
      activity associated with poly(ADP-ribose) polymerase-1.
AB  - Poly(ADP-ribose) polymerase-1 is a highly abundant nuclear enzyme implicated in
      transcription, DNA replication, and DNA repair through binding of nascent RNA and
      interactions with various factors. We found that purified fractions of
      recombinant human poly(ADP-ribose) polymerase-1 expressed in Escherichia coli
      possess yet another activity, a Mg(2+)-dependent DNA supercoil relaxation
      activity. Cleavage of recombinant poly(ADP-ribose) polymerase-1 by caspase-3, an
      apoptotic protease, reduced this activity, as did the removal of either of the
      two zinc finger motifs located in the N-terminal DNA-binding domain of poly(ADP
      ribose) polymerase-1. In addition, this activity was separated from E. coli
      topoisomerase I by gel-filtration column chromatography, suggesting that this
      activity is specifically associated with poly(ADP-ribose) polymerase-1. Because
      this relaxation activity did not require ATP and was resistant to VP16, a
      topoisomerase II inhibitor, this activity is closer to that of topoisomerase I.
      However, the supercoiled DNA relaxation activity associated with poly(ADP-ribose)
      polymerase-1 is distinct from that of human or E. coli topoisomerase I, as this
      activity could not completely remove superhelical tensions from plasmid DNA.
      Thus, we referred to this activity as topoisomerase I-like activity. This Mg(2+)
      dependent DNA supercoil relaxation activity was found to be sensitive to
      camptothecin, a mammalian topoisomerase I inhibitor.

PMID- 14715658
TI  - S-(2-chloroethyl)glutathione-generated p53 mutation spectra are influenced by
      differential repair rates more than sites of initial dna damage.
AB  - Several steps occur between the reaction of a chemical with DNA and a mutation,
      and each may influence the resulting mutation spectrum, i.e. nucleotides at which
      the mutations occur. The half-mustard S-(2-bro-moethyl)glutathione is the
      reactive conjugate implicated in ethylene dibromide-induced mutagenesis
      attributed to the glutathione-dependent pathway. A human p53-driven Ade reporter
      system in yeast was used to study the factors involved in producing mutations.
      The synthetic analog S-(2-chloroethyl)glutathione was used to produce DNA damage;
      the damage to the p53 exons was analyzed using a new fluorescence-based
      modification of ligation-mediated polymerase chain reaction and an automated
      sequencer. The mutation spectrum was strongly dominated by the G to A transition
      mutations seen in other organisms with S-(2-chloroethyl)glutathione or ethylene
      dibromide. The mutation spectrum clearly differed from the spontaneous spectrum
      or that derived from N-ethyl,N-nitrosourea. Distinct differences were seen
      between patterns of modification of p53 DNA exposed to the mutagen in vitro
      versus in vivo. In the four p53 exons in which mutants were analyzed, the major
      sites of mutation matched the sites with long half-lives of repair much better
      than the sites of initial damage. However, not all slowly repaired sites yielded
      mutations in part because of the lack of effect of mutations on phenotype. We
      conclude that the rate of DNA repair at individual nucleotides is a major factor
      in influencing the mutation spectra in this system. The results are consistent
      with a role of N(7)-guanyl adducts in mutagenesis.

PMID- 14715659
TI  - DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding
      site, sequence specificity, and internal binding to multimeric sites.
AB  - The human telomeric protein POT1 is known to bind single-stranded telomeric DNA
      in vitro and to participate in the regulation of telomere maintenance by
      telomerase in vivo. We examined the in vitro DNA binding features of POT1. We
      report that deleting the oligosaccharide/oligonucleotide-binding fold of POT1
      abrogates its DNA binding activity. The minimal binding site (MBS) for POT1 was
      found to be the telomeric nonamer 5'-TAGGGTTAG-3', and the optimal substrate is
      [TTAGGG](n (n > or = 2)). POT1 displays exceptional sequence specificity when
      binding to MBS, tolerating changes only at position 7 (T7A). Whereas POT1 binding
      to MBS or [TTAGGG](2) was enhanced by the proximity of a 3' end, POT1 was able to
      bind to a [TTAGGG](5) array when positioned internally. These data indicate that
      POT1 has a strong sequence preference for the human telomeric repeat tract and
      predict that POT1 can bind both the 3' telomeric overhang and the displaced
      TTAGGG repeats at the base of the t-loop.

PMID- 14715660
TI  - The NMR-derived solution structure of a new cationic antimicrobial peptide from
      the skin secretion of the anuran Hyla punctata.
AB  - Amphibian skin secretions constitute an important source of molecules for
      antimicrobial drug research in order to combat the increasing resistance of
      pathogens to conventional antibiotics. Among the various types of substances
      secreted by the dermal granular amphibian glands, there is a wide range of
      peptides and proteins, often displaying potent antimicrobial activities and
      providing an effective defense system against parasite infection. In the present
      work, we report the NMR solution structure and the biological activity of a
      cationic 14-residue amphiphilic alpha-helical polypeptide named Hylaseptin P1
      (HSP1), isolated from the skin secretion of the hylid frog Hyla punctata. The
      peptide antimicrobial activity was verified against Candida albicans,
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, whereas no
      significant lytic effect was detected toward red or white blood cells.

PMID- 14715661
TI  - p28, a novel IgE receptor-associated protein, is a sensor of receptor occupation
      by its ligand in mast cells.
AB  - Mast cells express the high affinity receptor for IgE (FcepsilonRI). Aggregation
      of this receptor by IgE and antigen leads to a signaling cascade resulting in the
      secretion of histamine, in the synthesis of other pro-inflammatory mediators such
      as leukotrienes and prostaglandins, and in the production of various cytokines,
      all of which participate in the development of the allergic reaction. In the last
      years, growing evidence accumulated that binding of IgEs to FcepsilonRI in itself
      induces active signals leading to mast cell survival, increased expression of
      FcepsilonRI, transient induction of histidine decarboxylase synthesis, and
      increased cell adhesion. The mechanisms underlying monomeric IgE signaling in the
      absence of receptor aggregation are still poorly understood. Here, we show that a
      protein of 28 kDa (p28) is physically and constitutively associated with
      FcepsilonRI in mast cells. Coimmunoprecipitation studies from (125)I surface
      labeled cells demonstrated that this association involves at least 50% of
      membrane-expressed FcepsilonRI. After the addition of monomeric IgE to the cells,
      the p28.FcepsilonRI complex dissociates almost completely in less than 2 min.
      This dissociation is temperature-sensitive and is not due to the recruitment of
      additional proteins to the complex. Stripping bound IgE from the cells by acidic
      treatment promotes a rapid reassociation between p28 and FcepsilonRI. Altogether,
      these data are consistent with a conformational regulation of the complex. Thus,
      p28 is a sensor for FcepsilonRI occupation by IgE on mast cells, and its
      dissociation from the receptor could represent an early step of monomeric IgE
      signaling.

PMID- 14715662
TI  - ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the
      setting of inflammation.
AB  - Angiogenesis is a critical component of the inflammatory response associated with
      a number of conditions. Angiopoietin-1 (Ang-1) is an angiogenic growth factor
      that promotes the chemotaxis of endothelial cells and facilitates the maturation
      of new blood vessels. Ang-1 expression is up-regulated in response to tumor
      necrosis factor-alpha (TNF-alpha). To begin to elucidate the underlying molecular
      mechanisms by which Ang-1 gene expression is regulated during inflammation, we
      isolated 3.2 kb of the Ang-1 promoter that contain regulatory elements sufficient
      to mediate induction of the promoter in response to TNF-alpha, interleukin-1beta,
      and endotoxin. Surprisingly, sequence analysis of this promoter failed to reveal
      binding sites for transcription factors that are frequently associated with
      mediating inflammatory responses, such as NF-kappaB, STAT, NFAT, or C/EBP.
      However, putative binding sites for ETS and AP-1 transcription factor family
      members were identified. Interestingly, among a panel of ETS factors tested in a
      transient transfection assay, only the ETS factor ESE-1 was capable of
      transactivating the Ang-1 promoter. ESE-1 binds to specific ETS sites within the
      Ang-1 promoter that are functionally important for transactivation by ESE-1. ESE
      1 and Ang-1 are induced in synovial fibroblasts in response to inflammatory
      cytokines, with ESE-1 induction slightly preceding that of Ang-1. Mutation of a
      high-affinity ESE-1 binding site leads to a marked reduction in Ang-1
      transactivation by ESE-1, inducibility by inflammatory cytokines, and DNA binding
      to the ESE-1 protein. Transcriptional profiling of cells transiently transfected
      with an ESE-1 expression vector demonstrates that the endogenous Ang-1 gene is
      directly inducible by ESE-1. Finally, Ang-1 and ESE-1 exhibit a similar and
      strong expression pattern in the synovium of patients with rheumatoid arthritis.
      Our results support a novel paradigm for the ETS factor ESE-1 as a
      transcriptional mediator of angiogenesis in the setting of inflammation.

PMID- 14715663
TI  - Potential role for Pex19p in assembly of PTS-receptor docking complexes.
AB  - Human Pex19p binds a broad spectrum of peroxisomal membrane proteins (PMPs). It
      has been proposed that this peroxin may: (i) act as a cycling PMP receptor
      protein, (ii) facilitate the insertion of newly synthesized PMPs into the
      peroxisomal membrane, or (iii) function as a chaperone to associate and/or
      dissociate complexes comprising integral PMPs already in the peroxisomal
      membrane. We previously demonstrated that human Pex19p binds peroxisomal integral
      membrane proteins at regions distinct from their sorting sequences. Here we
      demonstrate that a mutant of Pex13p that fails to bind to Pex19p nevertheless
      targets to and integrates into the peroxisomal membrane. In addition, through in
      vitro biochemical analysis, we show that Pex19p competes with Pex5p and Pex13p
      for binding to Pex14p, supporting a role for this peroxin in regulating
      assembly/disassembly of membrane-associated protein complexes. To further examine
      the molecular mechanism underlying this competition, six evolutionarily conserved
      amino acids in the Pex5p/Pex13p/Pex19p binding domain of Pex14p were subjected to
      site-directed mutagenesis and the corresponding mutants functionally analyzed.
      Our results indicate that the physically overlapping binding sites of Pex14p for
      Pex5p, Pex13p, and Pex19p are functionally distinct, suggesting that competition
      occurs through induction of structural changes, rather than through direct
      competition. Importantly, we also found that amino acid substitutions resulting
      in a strongly reduced binding affinity for Pex13p affect the peroxisomal
      localization of Pex14p.

PMID- 14715664
TI  - Revisiting the structure of the anti-neoplastic glucans of Mycobacterium bovis
      Bacille Calmette-Guerin. Structural analysis of the extracellular and boiling
      water extract-derived glucans of the vaccine substrains.
AB  - The attenuated strain of Mycobacterium bovis Bacille Calmette-Guerin (BCG), used
      worldwide to prevent tuberculosis and leprosy, is also clinically used as an
      immunotherapeutic agent against superficial bladder cancer. An anti-tumor
      polysaccharide has been isolated from the boiling water extract of the Tice
      substrain of BCG and tentatively characterized as consisting primarily of
      repeating units of 6-linked-glucosyl residues. Mycobacterium tuberculosis and
      other mycobacterial species produce a glycogen-like alpha-glucan composed of
      repeating units of 4-linked glucosyl residues substituted at some 6 positions by
      short oligoglucosyl units that also exhibits an anti-tumor activity. Therefore,
      the impression prevails that mycobacteria synthesize different types of anti
      neoplastic glucans or, alternatively, the BCG substrains are singular in
      producing a unique type of glucan that may confer to them their immunotherapeutic
      property. The present study addresses this question through the comparative
      analysis of alpha-glucans purified from the extracellular materials and boiling
      water extracts of three vaccine substrains. The polysaccharides were purified,
      and their structural features were established by mono- and two-dimensional NMR
      spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry of the enzymatic and chemical degradation products of the purified
      compounds. The glucans isolated by the two methods from the three substrains of
      BCG were shown to exhibit identical structural features shared with the glycogen
      like alpha-glucan of M. tuberculosis and other mycobacteria. Incidentally, we
      observed an occasional release of dextrans from Sephadex columns that may explain
      the reported occurrence of 6-substituted alpha-glucans in mycobacteria.

PMID- 14715665
TI  - Thermodynamics of oxidation-reduction reactions in mammalian nitric-oxide
      synthase isoforms.
AB  - The three mammalian nitric-oxide synthases produce NO from arginine in a reaction
      requiring 3 electrons per NO, which are supplied to the catalytic center from
      NADPH through reductase domains incorporating FAD and FMN cofactors. The isoforms
      share a common reaction mechanism and requirements for reducing equivalents but
      differ in regulation; the endothelial and neuronal isoforms are controlled by
      calcium/calmodulin modulation of the electron transfer system, while the
      inducible isoform binds calmodulin at all physiological Ca(2+) concentrations and
      is always on. The thermodynamics of electron transfer through the flavin domains
      in all three isoforms are basically similar. The major flavin states are FMN,
      FMNH., FMNH(2), FAD, FADH., and FADH(2). The FMN/FMNH. couple is high potential (
      approximately 100 mV) in all three isoforms and is unlikely to be catalytically
      competent; the other three flavin couples form a nearly isopotential group
      clustered around -250 mV. Reduction of the flavins by the pyridine nucleotide
      couple at -325 mV is thus moderately thermodynamically favorable. The
      ferri/ferroheme couple in all three isoforms is approximately -270 mV in the
      presence of saturating arginine. Ca(2+)/calmodulin has no effect on the
      potentials of any of the couples in endothelial nitric-oxide synthase (eNOS) or
      neuronal nitric-oxide synthase (nNOS). The pH dependence of the flavin couples
      suggests the presence of ionizable groups coupled to the flavin redox/protonation
      states.

PMID- 14715666
TI  - Modulation of amyloid precursor protein cleavage by cellular sphingolipids.
AB  - Lipid rafts and their component, cholesterol, modulate the processing of beta
      amyloid precursor protein (APP). However, the role of sphingolipids, another
      major component of lipid rafts, in APP processing remains undetermined. Here we
      report the effect of sphingolipid deficiency on APP processing in Chinese hamster
      ovary cells treated with a specific inhibitor of serine palmitoyltransferase,
      which catalyzes the first step of sphingolipid biosynthesis, and in a mutant LY-B
      strain defective in the LCB1 subunit of serine palmitoyltransferase. We found
      that in sphingolipid-deficient cells, the secretion of soluble APPalpha
      (sAPPalpha) and the generation of C-terminal fragment cleaved at alpha-site
      dramatically increased, whereas beta-cleavage activity remained unchanged, and
      the epsilon-cleavage activity decreased without alteration of the total APP
      level. The secretion of amyloid beta-protein 42 increased in sphingolipid
      deficient cells, whereas that of amyloid beta-protein 40 did not. All of these
      alterations were restored in sphingolipid-deficient cells by adding exogenous
      sphingosine and in LY-B cells by transfection with cLCB1. Sphingolipid deficiency
      increased MAPK/ERK activity and a specific inhibitor of MAPK kinase, PD98059,
      restored sAPPalpha level, indicating that sphingolipid deficiency enhances
      sAPPalpha secretion via activation of MAPK/ERK pathway. These results suggest
      that not only the cellular level of cholesterol but also that of sphingolipids
      may be involved in the pathological process of Alzheimer's disease by modulating
      APP cleavage.

PMID- 14715667
TI  - Ceramide-induced apoptosis by translocation, phosphorylation, and activation of
      protein kinase Cdelta in the Golgi complex.
AB  - Protein kinase C (PKC), a Ca(2+)/phospholipid-dependent protein kinase, is known
      as a key enzyme in various cellular responses, including apoptosis. However, the
      functional role of PKC in apoptosis has not been clarified. In this study, we
      focused on the involvement of PKCdelta in ceramide-induced apoptosis in HeLa
      cells and examined the importance of spatiotemporal activation of the specific
      PKC subtype in apoptotic events. Ceramide-induced apoptosis was inhibited by the
      PKCdelta-specific inhibitor rottlerin and also was blocked by knockdown of
      endogenous PKCdelta expression using small interfering RNA. Ceramide induced the
      translocation of PKCdelta to the Golgi complex and the concomitant activation of
      PKCdelta via phosphorylation of Tyr(311) and Tyr(332) in the hinge region of the
      enzyme. Unphosphorylatable PKCdelta (mutants Y311F and Y332F) could translocate
      to the Golgi complex in response to ceramide, suggesting that tyrosine
      phosphorylation is not necessary for translocation. However, ceramide failed to
      activate PKCdelta lacking the C1B domain, which did not translocate to the Golgi
      complex, but could be activated by tyrosine phosphorylation. These findings
      suggest that ceramide translocates PKCdelta to the Golgi complex and that
      PKCdelta is activated by tyrosine phosphorylation in the compartment.
      Furthermore, we utilized species-specific knockdown of PKCdelta by small
      interfering RNA to study the significance of phosphorylation of Tyr(311) and
      Tyr(332) in PKCdelta for ceramide-induced apoptosis and found that
      phosphorylation of Tyr(311) and Tyr(332) is indispensable for ceramide-induced
      apoptosis. We demonstrate here that the targeting mechanism of PKCdelta, dual
      regulation of both its activation and translocation to the Golgi complex, is
      critical for the ceramide-induced apoptotic event.

PMID- 14715668
TI  - Modification of proteins by isoketal-containing oxidized phospholipids.
AB  - Oxidative stress frequently leads to altered function of membrane proteins.
      Isoketals are highly reactive products of the isoprostane pathway of free radical
      induced lipid peroxidation that rapidly form covalent protein adducts and exhibit
      a remarkable proclivity to form protein cross links in vitro. Examination of
      isoketal adducts from an animal model of oxidative injury revealed that initial
      adducts were formed by isoketals esterified in phospholipids, representing a
      novel oxidative injury-associated modification of proteins by phospholipids.
      Maturation of adducts involved cleavage from phospholipids and conversion of
      adducts to a more stable chemical form that can be detected for extended periods.
      Because initial adducts were formed by phospholipid-esterified isoketals, the
      functional consequence of isoketal adduction was examined using a model membrane
      protein (a cardiac K(+) channel). These studies revealed that isoketal adduction
      profoundly altered protein function, inhibiting potassium current in a dose
      dependent manner. These findings indicate that phospholipid-esterified isoketals
      rapidly adduct membrane proteins and that such modification can alter protein
      function, suggesting a generalized cellular mechanism for alteration of membrane
      function as a consequence of oxidative stress.

PMID- 14715669
TI  - Kinetic study of the antiport mechanism of an Escherichia coli zinc transporter,
      ZitB.
AB  - ZitB is a member of the cation diffusion facilitator (CDF) family that mediates
      efflux of zinc across the plasma membrane of Escherichia coli. We describe the
      first kinetic study of the purified and reconstituted ZitB by stopped-flow
      measurements of transmembrane fluxes of metal ions using a metal-sensitive
      fluorescent indicator encapsulated in proteoliposomes. Metal ion filling
      experiments showed that the initial rate of Zn2+ influx was a linear function of
      the molar ratio of ZitB to lipid and was related to the concentration of Zn2+ or
      Cd2+ by a hyperbola with a Michaelis-Menten constant (K(m)) of 104.9 +/- 5.4
      microm and 90.1 +/- 3.7 microm, respectively. Depletion of proton stalled Cd2+
      transport down its diffusion gradient, whereas tetraethylammonium ion
      substitution for K+ did not affect Cd2+ transport, indicating that Cd2+ transport
      is coupled to H+ rather than to K+. H+ transport was inferred by the H+
      dependence of Cd2+ transport, showing a hyperbolic relationship with a Km of 19.9
      nm for H+. Applying H+ diffusion gradients across the membrane caused Cd2+ fluxes
      both into and out of proteoliposomes against the imposed H(+) gradients.
      Likewise, applying outwardly oriented membrane electrical potential resulted in
      Cd2+ efflux, demonstrating the electrogenic effect of ZitB transport. Taken
      together, these results indicate that ZitB is an antiporter catalyzing the
      obligatory exchange of Zn2+ or Cd2+ for H+. The exchange stoichiometry of metal
      ion for proton is likely to be 1:1.

PMID- 14715670
TI  - The identification and structure of the membrane-spanning domain of the
      Clostridium septicum alpha toxin.
AB  - Alpha toxin (AT) is a pore-forming toxin produced by Clostridium septicum that
      belongs to the unique aerolysin-like family of pore-forming toxins. The location
      and structure of the transmembrane domains of these toxins have remained elusive.
      Using deletion mutagenesis, cysteine-scanning mutagenesis and multiple
      spectrofluorimetric methods a membrane-spanning amphipathic beta-hairpin of AT
      has been identified. Spectrofluorimetric analysis of cysteine-substituted
      residues modified with an environmentally sensitive fluorescent probe via the
      cysteine sulfydryl showed that the side chains of residues 203-232 alternated
      between the aqueous milieu and the membrane core when the AT oligomer was
      inserted into membranes, consistent with the formation of an amphipathic
      transmembrane beta-hairpin. AT derivatives that contained deletions that removed
      up to 90% of the beta-hairpin did not form a pore but were similar to native
      toxin in all other aspects of the mechanism. Furthermore, a mutant of AT that
      contained an engineered disulfide, predicted to restrict the movement of the beta
      hairpin, functioned similarly to native toxin except that it did not form a pore
      unless the disulfide bond was reduced. Together these studies revealed the
      location and structure of the membrane-spanning domain of AT.

PMID- 14715671
TI  - Site-directed mutation of arginine 282 to glutamate uncouples the movement of
      peptides and protons by the rabbit proton-peptide cotransporter PepT1.
AB  - A conserved positive residue in the seventh transmembrane domain of the mammalian
      proton-coupled di- and tripeptide transporter PepT1 has been shown by site
      directed mutagenesis to be a key residue for protein function. Substitution of
      arginine 282 with a glutamate residue (R282E-PepT1) gave a protein at the plasma
      membrane of Xenopus laevis oocytes that was able to transport the non
      hydrolyzable dipeptide [3H]d-Phe-l-Gln, although unlike the wild type, the rate
      of transport by R282E-PepT1 was independent of the extracellular pH level, and
      the substrate could not be accumulated above equilibrium. The binding affinity of
      the mutant transport protein was unchanged from the wild type. Thus, R282E-Pept1
      appears to have been changed from a proton-driven to a facilitated transporter
      for peptides. In addition, peptide transport by R282E-PepT1 still induced
      depolarization as measured by microelectrode recordings of membrane potential. A
      more detailed study by two-electrode voltage clamping revealed that R282E-PepT1
      behaved as a peptide-gated non-selective cation channel with the ion selectivity
      series lithium > sodium > N-methyl-d-glucamine at pH 7.4. There was also a proton
      conductance (comparing pH 7.4 and 8.4), and at pH 5.5 the predominant conductance
      was for potassium ions. Therefore, it can be concluded that changing arginine 282
      to a glutamate not only uncouples the cotransport of protons and peptides of the
      wild-type PepT1 but also creates a peptide-gated cation channel in the protein.

PMID- 14715672
TI  - Sensing vascular distension in skeletal muscle by slow conducting afferent
      fibers: neurophysiological basis and implication for respiratory control.
AB  - This review examines the evidence that skeletal muscles can sense the status of
      the peripheral vascular network through group III and IV muscle afferent fibers.
      The anatomic and neurophysiological basis for such a mechanism is the following:
      1) a significant portion of group III and IV afferent fibers have been found in
      the vicinity and the adventitia of the arterioles and the venules; 2) both of
      these groups of afferent fibers can respond to mechanical stimuli; 3) a
      population of group III and IV fibers stimulated during muscle contraction has
      been found to be inhibited to various degrees by arterial occlusion; and 4) more
      recently, direct evidence has been obtained showing that a part of the group IV
      muscle afferent fibers is stimulated by venous occlusion and by injection of
      vasodilatory agents. The physiological relevance of sensing local distension of
      the vascular network at venular level in the muscles is clearly different from
      that of the large veins, since the former can directly monitor the degree of
      tissue perfusion. The possible involvement of this sensing mechanism in
      respiratory control is discussed mainly in the light of the ventilatory effects
      of peripheral vascular occlusions during and after muscular exercise. It is
      proposed that this regulatory system anticipates the chemical changes that would
      occur in the arterial blood during increased metabolic load and attempts to
      minimize them by adjusting the level of ventilation to the level of muscle
      perfusion, thus matching the magnitudes of the peripheral and pulmonary gas
      exchange.

PMID- 14715673
TI  - Considerations on the history dependence of muscle contraction.
AB  - When a skeletal muscle that is actively producing force is shortened or
      stretched, the resulting steady-state isometric force after the dynamic phase is
      smaller or greater, respectively, than the purely isometric force obtained at the
      corresponding final length. The cross-bridge model of muscle contraction does not
      readily explain this history dependence of force production. The most accepted
      proposal to explain both, force depression after shortening and force enhancement
      after stretch, is a nonuniform behavior of sarcomeres that develops during and
      after length changes. This hypothesis is based on the idea of instability of
      sarcomere lengths on the descending limb of the force-length relationship.
      However, recent evidence suggests that skeletal muscles may be stable over the
      entire range of active force production, including the descending limb of the
      force-length relationship. The purpose of this review was to critically evaluate
      hypotheses aimed at explaining the history dependence of force production and to
      provide some novel insight into the possible mechanisms underlying these
      phenomena. It is concluded that the sarcomere nonuniformity hypothesis cannot
      always explain the total force enhancement observed after stretch and likely does
      not cause all of the force depression after shortening. There is evidence that
      force depression after shortening is associated with a reduction in the
      proportion of attached cross bridges, which, in turn, might be related to a
      stress-induced inhibition of cross-bridge attachment in the myofilament overlap
      zone. Furthermore, we suggest that force enhancement is not associated with
      instability of sarcomeres on the descending limb of the force-length relationship
      and that force enhancement has an active and a passive component. Force
      depression after shortening and force enhancement after stretch are likely to
      have different origins.

PMID- 14715674
TI  - Respiratory measurements of cardiac output: from elegant idea to useful test.
AB  - The measurement of cardiac output was first proposed by Fick, who published his
      equation in 1870. Fick's calculation called for the measurement of the contents
      of oxygen or CO2 in pulmonary arterial and systemic arterial blood. These values
      could not be determined directly in human subjects until the acceptance of
      cardiac catheterization as a clinical procedure in 1940. In the meanwhile,
      several attempts were made to perfect respiratory methods for the indirect
      determination of blood-gas contents by respiratory techniques that yielded
      estimates of the mixed venous and pulmonary capillary gas pressures. The
      immediate uptake of nonresident gases can be used in a similar way to calculate
      cardiac output, with the added advantage that they are absent from the mixed
      venous blood. The fact that these procedures are safe and relatively nonintrusive
      makes them attractive to physiologists, pharmacologists, and sports scientists as
      well as to clinicians concerned with the physiopathology of the heart and lung.
      This paper outlines the development of these techniques, with a discussion of
      some of the ways in which they stimulated research into the transport of gases in
      the body through the alveolar membrane.

PMID- 14715675
TI  - Activity of tongue muscles during respiration: it takes a village?

PMID- 14715676
TI  - Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor
      cells in vitro.
AB  - Epidemiological studies report that regular physical activity can reduce the risk
      for prostate cancer, the most common solid-tumor cancer in US men. Regular
      exercise alters the serum IGF axis in vivo and reduces cell proliferation while
      increasing apoptosis in serum-stimulated LNCaP prostate cancer cells in vitro.
      The present study tests the hypothesis that these effects on tumor cell lines are
      mediated by enhancement of the function of the p53 gene known to arrest cell
      growth and induce apoptosis. When LNCaP cells were cultured in exercise serum and
      compared with control serum, cell growth was reduced by 27%, and there was a
      similar 33% decrease in proliferating cell nuclear antigen protein, a marker for
      cell cycling. Apoptosis was increased by 371% with the exercise serum, and there
      was a 100% increase in p53 protein (75.2 +/- 2.0 vs. 38.2 +/- 2.0 pg/microg
      protein). When serum was used to stimulate LN-56 cells, a cell line with
      nonfunctional p53 derived from LNCaP, no significant reduction in cell growth or
      increase in apoptosis with the exercise serum was observed. These results
      indicate that exercise training alters serum factors in vivo that increase
      cellular p53 protein content and is associated with reduced growth and induced
      apoptosis in LNCaP prostate cancer cells in vitro.

PMID- 14715677
TI  - Peroxynitrite does not impair pulmonary and systemic vascular responses.
AB  - The effects of peroxynitrite (ONOO-) on vascular responses were investigated in
      the systemic and hindquarters vascular bed and in the isolated perfused rat lung.
      Intravenous injections of ONOO- decreased systemic arterial pressure, and
      injections of ONOO- into the hindquarters decreased perfusion pressure in a dose
      related manner. Injections of ONOO- into the lung perfusion circuit increased
      pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset,
      short in duration, and repeatable without exhibiting tachyphylaxis. Repeated
      injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses
      to endothelium-dependent vasodilators or other vasoactive agonists and did not
      alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium
      nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures.
      Pulmonary and hindquarters responses to ONOO- were not altered by a
      cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid.
      These results demonstrate that ONOO- has significant pulmonary vasoconstrictor,
      systemic vasodepressor, and vasodilator activity; that short-term repeated
      exposure does impair vascular responsiveness; and that responses to ONOO- are not
      dependent on cyclooxygenase product release.

PMID- 14715678
TI  - The two mechanisms of intercostal muscle action on the lung.
AB  - The mechanisms of respiratory action of the intercostal muscles were studied by
      measuring the effect of external forces (F) applied to the ribs and by modeling
      the effect of F exerted by the intercostal muscles. In five dogs, with the airway
      occluded, cranial F were applied to individual rib pairs, from the 2nd to the
      11th rib pair, and the change in airway opening pressure (Pao) was measured. The
      ratio Pao/F increases with increasing rib number in the upper ribs (2nd to 5th)
      and decreases in the lower ribs (5th to 11th). These data were incorporated into
      a model for the geometry of the ribs and intercostal muscles, and Pao/F was
      calculated from the model. For interspaces 2-8, the calculated values agree
      reasonably well with previously measured values. From the modeling, two
      mechanisms of intercostal muscle action are identified. One is the well-known
      Hamberger mechanism, modified to account for the three-dimensional geometry of
      the rib cage. This mechanism depends on the slant of an intercostal muscle
      relative to the ribs and on the resulting difference between the moments applied
      to the upper and lower ribs that bound each interspace. The second is a new
      mechanism that depends on the difference between the values of Pao/F for the
      upper and lower ribs.

PMID- 14715679
TI  - Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in
      postmenopausal women.
AB  - We sought to determine whether common genetic variations at the beta2 (beta2-AR,
      Gln27Glu) and beta3 (beta3-AR, Trp64Arg) adrenergic receptor gene loci were
      associated with cardiovascular (CV) hemodynamics during maximal and submaximal
      exercise. CV hemodynamics were assessed in 62 healthy postmenopausal women (20
      sedentary, 22 physically active, and 20 endurance athletes) during treadmill
      exercise at 40, 60, 80, and 100% maximal O2 uptake using acetylene rebreathing to
      quantify cardiac output. The beta2-AR genotype and habitual physical activity
      (PA) levels interacted to significantly associate with arteriovenous O2
      difference (a-vDO2) during submaximal exercise (P = 0.05), with the highest
      submaximal exercise a-vDO2 in sedentary women homozygous for the beta2-AR Gln
      allele and no genotype-dependent differences in submaximal exercise a-vDO2 in
      physically active and athletic women. The beta2-AR genotype also was
      independently associated with a-vDO2 during submaximal (P = 0.004) and
      approximately 100% maximal O2 uptake exercise (P = 0.006), with a 1.2-2 ml/100 ml
      greater a-vDO2 in the Gln/Gln than in the Glu/Glu genotype women. The beta3-AR
      genotype, independently or interacting with habitual PA levels, was not
      significantly associated with any CV hemodynamic variables during submaximal or
      maximal exercise. Thus it appears that the beta2-AR genotype, both independently
      and interacting with habitual PA levels, is significantly associated with a-vDO2
      during exercise in postmenopausal women, whereas the beta3-AR genotype does not
      appear to be associated with any maximal or submaximal exercise CV hemodynamic
      responses in postmenopausal women.

PMID- 14715680
TI  - Mathematical modeling of airway epithelial wound closure during cyclic mechanical
      strain.
AB  - The repair of airway epithelium after injury is crucial in restoring epithelial
      barrier integrity. Because the airways are stretched and compressed due to
      changes in both circumferential and longitudinal dimensions during respiration
      and may be overdistended during mechanical ventilation, we investigated the
      effect of cyclic strain on the repair of epithelial wounds. Both cyclic
      elongation and compression significantly slowed repair, with compression having
      the greatest effect. We developed a mathematical model of the mechanisms involved
      in airway epithelial cell wound closure. The model focuses on the differences in
      spreading, migration, and proliferation with cyclic strain by using separate
      parameters for each process and incorporating a time delay for the mitotic
      component. Numerical solutions of model equations determine the shape of the
      diffusive wave solutions of cell density that correspond to the influx of cells
      into the wound during the initial phase of reepithelialization. Model simulations
      were compared with experimental measurements of cell density and the rate of
      wound closure, and parameters were determined based on measurements from airway
      epithelial cells from several different sources. The contributions of spreading,
      migration, and mitosis were investigated both numerically and experimentally by
      using cytochalasin D to inhibit cell motility and mitomycin C to inhibit
      proliferation.

PMID- 14715681
TI  - Bioactive nitric oxide concentration does not increase during reactive hyperemia
      in human skin.
AB  - This study examined whether nitric oxide (NO) is involved in the cutaneous
      response to reactive hyperemia (RH) in the human forearm. We enrolled seven
      healthy volunteers. NO concentrations were monitored using a NO selective
      amperometric electrode (ISO-NOP200, World Precision Instruments) inserted into
      the skin of the forearm. Laser-Doppler flowmetry (Moor Instruments) was used for
      monitoring skin blood flow (SkBF) at the same site. SkBF and NO levels were
      monitored and recorded continuously throughout the experiment. An intradermal
      microdialysis probe was inserted adjacent to the NO electrode for drug delivery.
      Data collection began 140 min after the NO electrodes and microdialysis probes
      were inserted. RH was achieved by the inflation of a blood pressure cuff to 25
      mmHg above systolic pressure for 7 min after which the pressure in the cuff was
      abruptly released. Acetylcholine (ACh) was given by microdialysis probe at the
      end of RH study to verify the ability of the electrode system to detect changes
      in the NO concentration. SkBF and NO data before RH and immediately, 2, 5, 7, and
      10 min after cuff deflation were used for analysis. SkBF increased immediately
      after release of the occlusion (P < 0.0001) and remained elevated for 2 min. No
      significant NO changes occurred with the increases in LDF. ACh induced increases
      in both SkBF and NO (P < 0.000 and P < 0.037, respectively). We conclude that RH
      increases SkBF by mechanisms that do not require a measurable increase in NO
      concentrations.

PMID- 14715682
TI  - Susceptibility to sarcomere injury induced by single stretches of maximally
      activated muscles of mdx mice.
AB  - The purpose was to investigate the contribution of mechanical damage to
      sarcomeres to the greater susceptibility of dystrophic muscle fibers to
      contraction-induced injury. Single stretches provide an effective method for
      studying mechanical factors that contribute to the initiation of contraction
      induced injury. We hypothesized that, after single stretches, the deficits in
      isometric force would be greater for muscles of mdx than C57BL/10 mice, whereas
      membrane damage would be minimal for all muscles. Extensor digitorum longus (EDL)
      and soleus muscles of mice were removed under anesthesia with Avertin
      (tribromoethanol). During the plateau of a maximum isometric contraction in
      vitro, muscles were stretched through single strains of 20-60% fiber length.
      Isometric force was remeasured 1 min later, and muscles were then incubated in
      procion orange dye to identify fibers with membrane damage. Force deficits at 1
      min were two- to threefold greater for EDL muscles of mdx compared with C57BL/10
      mice, whereas no significant differences were observed between soleus muscles of
      mdx and C57BL/10 mice. For all muscles, membrane damage was minimal and not
      significantly increased by single stretches for either strain of mice. These data
      support a critical role of dystrophin maintaining sarcomere stability in EDL
      muscles, whereas soleus muscles retain abilities, in the absence of dystrophin,
      not different from control muscles to resist sarcomere damage.

PMID- 14715683
TI  - Effects of modulators of sarcoplasmic Ca2+ release on the development of skeletal
      muscle fatigue.
AB  - The reduced release of Ca2+ from sarcoplasmic reticulum (SR) is considered a
      major determinant of muscle fatigue. In the present study, we investigated
      whether the presence of dantrolene, an established inhibitor of SR Ca2+ release,
      or caffeine, a drug facilitating SR Ca2+ release, modifies muscle fatigue
      development. Accordingly, the effects of Ca2+ release modulators were analyzed in
      vitro in mouse fast-twitch [extensor digitorum longus (EDL)] and slow-twitch
      (soleus) muscles, fatigued by repeated short tetani (40 Hz for 300 ms, 0.5 s(-1)
      in soleus and 60 Hz for 300 ms, 0.3 s(-1) in EDL, for 6 min). Caffeine produced a
      substantial increase of tetanic tension of both EDL and soleus muscles, whereas
      dantrolene decreased tetanic tension only in EDL muscle. In both EDL and soleus
      muscles, 5 microM dantrolene did not affect fatigue development, whereas 20
      microM dantrolene produced a positive staircase during the first 3 min of
      stimulation in EDL muscle and a slowing of fatigue development in soleus muscle.
      The development of the positive staircase was abolished by the addition of 15
      microM ML-7, a selective inhibitor of myosin light chain kinase. On the other
      hand, caffeine caused a larger and faster loss of tension in both EDL and soleus
      muscles. The results seem to indicate that the changes in fatigue profile induced
      by caffeine or dantrolene are mainly due to the changes in the initial tetanic
      tension caused by the drugs, with the resulting changes in the level of
      contraction-dependent factors of fatigue, rather than to changes in the SR Ca2+
      release during fatigue development.

PMID- 14715684
TI  - Model of forced expiratory flows and airway geometry in infants.
AB  - Early measurements of autopsied lungs from infants, children, and adults
      suggested that the ratio of peripheral to central airway resistance was higher in
      infants than older children and adults. Recent measurements of forced expiration
      suggest that infants have high flows relative to lung volume. We employed a
      computational model of forced expiratory flow along with physiological and
      anatomic data to evaluate whether the infant lung is a uniformly scaled-down
      version of the adult lung. First, we uniformly scaled an existing computational
      model of adult forced expiration to estimate forced expiratory flows (FEF) and
      density dependence for an 18-mo-old infant. The values obtained for FEF and
      density dependence were significantly lower than those reported for healthy 18-mo
      old infants. Next, we modified the model for the infant lung to reproduce
      standard indexes of expiratory flow [forced expiratory volume in 0.5 s
      (FEV(0.5)), FEFs after exhalation of 50 and 75% forced vital capacity, FEF
      between 25 and 75% expired volume] for this age group. The airway sizes obtained
      for the infant lung model that produced accurate physiological measurements were
      similar to anatomic data available for this age and larger than those in the
      scaled model. Our findings indicate that the airways in the infant lung model
      differ from those in the scaled model, i.e., middle and peripheral airway sizes
      are larger than result from uniform downscaling of the adult lung model. We show
      that the infant lung model can be made to reproduce individual flow-volume curves
      by adjusting lumen area generation by generation.

PMID- 14715685
TI  - Equation for osmotic pressure of serum protein (fractions).
AB  - The colloid or protein osmotic pressure (Pi) is a function of protein molarity
      (linear) and of Donnan and other effects. Albumin is the major osmotic protein,
      but also globulins influence Pi. Equations based on concentrations of albumin and
      nonalbumin (globulin concentration + fibrinogen concentration) protein
      approximate Pi better than albumin alone. Globulins have a wide range of
      molecular weights, and a 1956 diagram indicated that Pi of globulin fractions
      decreased in the order alpha1-, alpha2-, beta-, and gamma-globulin. The molecular
      weight of the serum protein fractions had been extrapolated, so van't Hoff's law
      and nonlinear regression analysis of the curves permitted expression of the
      diagram as an equation: product Pi(s,Ott,2 degrees
      C,cmH2O)=x(alb)(0.338C(tot)+0.00339C(tot)(2))+x(alpha1)(0.518C(tot)+0.0107C(tot)(
      ))+x(alpha2)(0.203C(tot)+0.00155C(tot)(2))+x(beta)(0.187C(tot)+0.000577C(tot)(2))
      x(gamma)(0.161C(tot)+0.000223C(tot)(2)), where Pi(s,Ott,2 degrees C,cmH2O) is Pi
      of serum at 2 degrees C (in cmH2O) computed from the 1956 diagram, C(tot) is the
      concentration (g/l) of total protein in serum, and x(alb), x(alpha1), x(alpha2),
      x(beta), and x(gamma) are the fractions of albumin, alpha1-, alpha2-, beta-, and
      gamma-globulin, respectively. At one and the same concentration of fractions,
      Pi("Ott") decreases in the order alpha1-globulin, albumin, alpha2-globulin, beta
      globulin, and gamma-globulin.

PMID- 14715686
TI  - Functional genomics approach to hypoxia signaling.
AB  - Mammalian cells require a constant supply of oxygen to maintain energy balance,
      and sustained hypoxia can result in cell death. It is therefore not surprising
      that sophisticated adaptive mechanisms have evolved that enhance cell survival
      during hypoxia. During the past few years, there have been a growing number of
      reports on hypoxia-induced transcription of specific genes. In this review, we
      describe a unique experimental approach that utilizes focused cDNA libraries
      coupled to microarray analyses to identify hypoxia-responsive signal transduction
      pathways and genes that confer the hypoxia-tolerant phenotype. We have used the
      subtractive suppression hybridization (SSH) method to create a cDNA library
      enriched in hypoxia-regulated genes in oxygen-sensing pheochromocytoma cells and
      have used this library to create microarrays that allow us to examine hundreds of
      genes at a time. This library contains over 300 genes and expressed sequence tags
      upregulated by hypoxia, including tyrosine hydroxylase, vascular endothelial
      growth factor, and junB. Hypoxic regulation of these and other genes in the
      library has been confirmed by microarray, Northern blot, and real-time PCR
      analyses. Coupling focused SSH libraries with microarray analyses allows one to
      specifically study genes relevant to a phenotype of interest while reducing much
      of the biological noise associated with these types of studies. When used in
      conjunction with high-throughput, dye-based assays for cell survival and
      apoptosis, this approach offers a rapid method for discovering validated
      therapeutic targets for the treatment of cardiovascular disease, stroke, and
      tumors.

PMID- 14715687
TI  - Signal transduction by heme-containing PAS-domain proteins.
AB  - The most common physiological strategy for detecting the gases oxygen, carbon
      monoxide, and nitric oxide is signal transduction by heme-based sensors, a broad
      class of modular proteins in which a heme-binding domain governs the activity of
      a neighboring transmitter domain. Different structures are possible for the heme
      binding domains in these sensors, but, so far, the Per-ARNT-Sim motif, or PAS
      domain, is the one most commonly encountered. Heme-binding PAS (heme-PAS) domains
      can accomplish ligand-dependent switching of a variety of partner domains,
      including histidine kinase, phosphodiesterase, and basic helix-loop-helix (bHLH)
      DNA-binding modules. Proteins with heme-PAS domains occur in all kingdoms of life
      and are quite diverse in their physiological roles. Examples include the neuronal
      bHLH-PAS carbon monoxide sensor NPAS2 that is implicated in the mammalian
      circadian clock, the acetobacterial oxygen sensor AxPDEA1 that directs cellulose
      production, and the rhizobial oxygen sensor FixL, which governs nitrogen
      fixation. What factors determine the range of detection of these sensors? How do
      they transduce their signal? This review examines the recent advances in
      answering these questions.

PMID- 14715688
TI  - Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of
      brain stem neurons.
AB  - Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures
      are routinely used for chemical denervation of peripheral O2 receptors in in vivo
      studies of respiratory control. The underlying assumption whenever using
      hyperoxia is that there are no direct effects of molecular O2 and reactive O2
      species (ROS) on brain stem function. In addition, control superfusates used
      routinely for in vitro studies of neurons in brain slices are, in fact,
      hyperoxic. Again, the assumption is that there are no direct effects of O2 and
      ROS on neuronal activity. Research contradicts this assumption by demonstrating
      that O2 has central effects on the brain stem respiratory centers and several
      effects on neurons in respiratory control areas; these need to be considered
      whenever hyperoxia is used. This mini-review summarizes the long-recognized, but
      seldom acknowledged, paradox of respiratory control known as hyperoxic
      hyperventilation. Several proposed mechanisms are discussed, including the recent
      hypothesis that hyperoxic hyperventilation is initiated by increased production
      of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in
      the solitary complex. Hyperoxic hyperventilation may provide clues into the
      fundamental role of redox signaling and ROS in central control of breathing;
      moreover, oxidative stress may play a role in respiratory control dysfunction.
      The practical implications of brain stem O2 and ROS sensitivity are also
      considered relative to the present uses of hyperoxia in respiratory control
      research in humans, animals, and brain stem tissues. Recommendations for future
      research are also proposed.

PMID- 14715690
TI  - Vascular oxygen sensing: detection of novel candidates by proteomics and organ
      culture.
AB  - We have shown that the specific inhibition of hypoxia-induced relaxation by organ
      culture in porcine coronary arteries can be mimicked by treatment of control
      vessels with the protein synthesis inhibitor, cycloheximide. We hypothesize that
      organ culture of vascular smooth muscle results in the decreased expression of
      proteins that are critical for vascular oxygen sensing. Using two-dimensional gel
      electrophoresis and mass spectroscopy, we identified such candidate proteins. The
      expressions of the smooth muscle-specific protein, SM22, and tropomyosin are
      decreased after 24 h in organ culture. These results were confirmed by Western
      blot analysis. Other smooth muscle proteins (actin and calponin) exhibited little
      change. We also demonstrate a 50% downregulation in the small G protein, Rho, a
      potent modulator of Ca(2+)-independent force. These results indicate that organ
      culture preferentially inhibits the expression of certain smooth muscle proteins.
      This change in protein expression after organ culture correlates with the
      specific inhibition of hypoxic vasorelaxation. These results provide novel target
      pathways for investigation that are potentially important for vascular oxygen
      sensing.

PMID- 14715691
TI  - Spontaneous fusion of cells between species yields transdifferentiation and
      retroviral transfer in vivo.
AB  - Human cells can fuse with damaged or diseased somatic cells in vivo. Whether
      human cells fuse in vivo in the absence of disease and with cells of disparate
      species is unknown. Such a question is of current interest because blood
      exchanges between species through direct physical contact, via insect vectors or
      parasitism, are thought to underlie the transmission of zoonotic agents. In a
      model of human-pig chimerism, we show that some human hematopoietic stem cells
      engrafted in pigs contain both human and porcine chromosomal DNA. These hybrid
      cells divide, express human and porcine proteins, and contribute to porcine
      nonhematopoietic tissues. In addition, the hybrid cells contain porcine
      endogenous retroviral DNA sequences and are able to transmit this virus to
      uninfected human cells in vitro. Thus, spontaneous fusion can occur in vivo
      between the cells of disparate species and in the absence of disease. The ability
      of these cell hybrids to acquire and transmit retroviral elements together with
      their ability to integrate into tissues could explain genetic recombination and
      generation of novel pathogens. * differentiation * fusion * retrovirus

PMID- 14715692
TI  - A novel homologous recombination system to study 92 kDa type IV collagenase
      transcription demonstrates that the NF-kappaB motif drives the transition from a
      repressed to an activated state of gene expression.
AB  - The 92-kDa type IV collagenase (MMP-9) contributes to tissue remodeling in both
      physiology and pathology. Previous studies on the transcriptional regulation of
      this gene have used transiently transfected promoter-reporter constructs.
      However, this approach suffers from several limitations including (a) multiple
      copies of the plasmid and (b) the plasmid is not genomically integrated and
      consequently poorly chromatinized. We developed a novel system for studying MMP-9
      transcription in which a single copy of a MMP-9 promoter-luciferase construct(s)
      is integrated at an identical genomic locus in HT1080 cells by homologous
      recombination. We report that the activity of a genomic-integrated 2.2 kb MMP-9
      promoter sequence mirrors expression of the endogenous MMP-9 gene in response to
      both physiological and pharmacological (curcumin) cues. Further, when constrained
      into chromatin, the integrated NF-kappaB-mutated MMP-9 promoter is repressed by
      PMA, a situation not apparent using nonintegrated plasmids. Thus, we have
      developed a novel method for studying MMP-9 expression that overcomes some of the
      limitations associated with transient transfection approaches and which may be of
      utility in screening for agents that repress the expression of this gene.

PMID- 14715693
TI  - Troponin T as a marker of differentiation revealed by proteomic analysis in renal
      arterioles.
AB  - Renovascular hypertension is characterized by stenosis of the renal artery and
      high plasma renin levels. The renal phenotype is characterized by high levels of
      renin in the hypoperfused kidney due to the recruitment of renin-producing cells
      along the afferent arterioles. This increase in myoepithelioid cells is due
      mainly to the differentiation of existing smooth muscle cells with acquisition of
      a secretory phenotype. To understand the molecular mechanisms involved in this
      recruitment, we used the established rat model of renovascular hypertension known
      as the two-kidney, one-clip model in the Lewis rat. Renal arterioles were
      isolated using magnetized iron suspension. Differential proteomic analysis was
      performed using 2-D polyacrylamide gel electrophoresis followed by mass
      spectrometry. Comparative analysis of soluble proteins extracted from afferent
      arterioles of clipped and contralateral kidneys showed 14 proteins significantly
      differentially expressed by at least a factor of 2. These proteins were
      identified by mass spectrometry. The most striking protein revealed by proteomics
      is troponin T, which is down-regulated in the afferent arterioles of the clipped
      kidney. Confocal microscopy showed that troponin T is specific of the smooth
      muscle phenotype and absent in the myoepithelioid phenotype. Our data suggest
      that troponin T is only present in renal smooth muscle cells.

PMID- 14715694
TI  - The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein
      coupled receptors.
AB  - FTY720 is an immunosuppressant that reduces circulating levels of naive
      lymphocytes by increasing their localization and sequestration in secondary
      lymphoid organs. It is considered to be an agonist for sphingosine 1-phosphate
      (S1P) G protein-coupled receptors (GPCRs) after phosphorylation at micromolar
      concentrations. We now describe its nonagonist and noncompetitive inhibitory
      activity at low nanomolar concentrations for types 1 and 5 S1P-GPCRs and of
      moderate potency for type 2 S1P-GPCRs. FTY720 blocks S1P signaling through
      S1P1,2,5 by inducing their internalization and intracellular partial degradation
      without affecting S1P3 or S1P4. S1P-R internalization is maximal several hours
      after only seconds of incubation with FTY720 at 37 degrees C and washing, and
      continues for days before recovery of surface expression and functions. The
      timing and extent of S1P-R internalization are highly dependent on FTY720
      concentration. FTY720 is therefore an S1P-GPCR-selective and noncompetitive
      inhibitor with a unique mechanism of action.

PMID- 14715695
TI  - Prenatal choline supplementation advances hippocampal development and enhances
      MAPK and CREB activation.
AB  - Choline is an essential nutrient for animals and humans. Previous studies showed
      that supplementing the maternal diet with choline during the second half of
      gestation in rats permanently enhances memory performance of the adult offspring.
      Here we show that prenatal choline supplementation causes a 3-day advancement in
      the ability of juvenile rats to use relational cues in a water maze task,
      indicating that the treatment accelerates hippocampal maturation. Moreover,
      phosphorylation and therefore activation of hippocampal mitogen-activated protein
      kinase (MAPK) and cAMP-response element binding protein (CREB) in response to
      stimulation by glutamate, N-methyl-D-aspartate, or depolarizing concentrations of
      K+ were increased by prenatal choline supplementation and reduced by prenatal
      choline deficiency. These data provide the first evidence that developmental
      plasticity of the hippocampal MAPK and CREB signaling pathways is controlled by
      the supply of a single essential nutrient, choline, during fetal development and
      point to these pathways as candidate mechanisms for the developmental and long
      term cognitive enhancement induced by prenatal choline supplementation.

PMID- 14715696
TI  - Evidence of melatonin synthesis by human lymphocytes and its physiological
      significance: possible role as intracrine, autocrine, and/or paracrine substance.
AB  - It has been historically assumed that the pineal gland is the major source of
      melatonin (N-acetyl-5-methoxytryptamine) in vertebrates. Melatonin plays a
      central role in fine-tuning circadian rhythms in vertebrate physiology. In
      addition, melatonin shows a remarkable functional versatility exhibiting
      antioxidant, oncostatic, antiaging, and immunomodulatory properties. Melatonin
      has been identified in a wide range of organisms from bacteria to human beings.
      Its biosynthesis from tryptophan involves four well-defined intracellular steps
      catalyzed by tryptophan hydroxylase, aromatic amino acid decarboxylase, serotonin
      N-acetyltransferase, and hydroxyindole-O-methyltransferase. Here, for the first
      time, we document that both resting and phytohemagglutinin-stimulated human
      lymphocytes synthesize and release large amounts of melatonin, with the melatonin
      concentration in the medium increasing up to five times the nocturnal
      physiological levels in human serum. Moreover, we show that the necessary
      machinery to synthesize melatonin is present in human lymphocytes. Furthermore,
      melatonin released to the culture medium is synthesized in the cells, because
      blocking the enzymes required for its biosynthesis or inhibiting protein
      synthesis in general produced a significant reduction in melatonin release.
      Moreover, this inhibition caused a decrease in IL-2 production, which was
      restored by adding exogenous melatonin. These findings indicate that in addition
      to pineal gland, human lymphoid cells are an important physiological source of
      melatonin and that this melatonin could be involved in the regulation of the
      human immune system, possibly by acting as an intracrine, autocrine, and/or
      paracrine substance.

PMID- 14715698
TI  - High-frequency stimulation of both zona incerta and subthalamic nucleus induces a
      similar normalization of basal ganglia metabolic activity in experimental
      parkinsonism.
AB  - High-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates
      dramatically motor symptoms in Parkinson's disease, and recently it has been
      suggested that zona incerta (ZI) stimulation might be as beneficial to patients.
      We used in situ cytochrome oxidase (CoI) mRNA hybridization to investigate and
      compare the effects of HFS of the STN and the ZI on metabolic activity of the
      STN, globus pallidus (GP), and substantia nigra reticulata (SNr) in normal rats
      as well as in rats with 6-hydroxydopamine (6-OHDA) lesion, an animal model of
      Parkinson's disease. In normal rats, HFS of the STN, as well as of the ZI,
      induced a significant decrease in CoI mRNA expression within the STN and SNr but
      an increase within the GP. In 6-OHDA rats, HFS of the STN reversed dopamine
      denervation-induced changes in the expression of CoI mRNA in the STN, SNr, and
      GP. Similar results were obtained with HFS of the ZI except for the STN, which
      showed only a trend toward normalization. These data suggest that the ZI, as well
      as the STN, are implicated in the functional mechanism of HFS supporting the
      involvement of GABA transmission for the reduction of neuronal activity in the
      basal ganglia output structures.

PMID- 14715697
TI  - Synthesis of nitric oxide in postganglionic myenteric neurons during endotoxemia:
      implications for gastric motor function in rats.
AB  - We have investigated the mechanisms underlying acute changes in gastric motor
      function triggered by endotoxemia. In fundal strips from rats pre-treated with
      endotoxin (40 microg/kg, i.p. 30 min), mechanical activity was analyzed and the
      source of nitric oxide (NO) was visualized by confocal microscopy of tissue
      loaded with the fluorescent dye DAF-FM. NOS expression was determined by
      quantitative RT-PCR and Western blot, and enzyme activity by the citrulline
      assay. Strips from endotoxin-treated rats were hypo-contractile. This was
      prevented by pre-incubation with the neurotoxin tetrodotoxin, the gangliar
      blocker hexamethonium, or non-selective and neuronal-specific NOS inhibitors (L
      NOARG and TRIM, respectively). The soluble guanylyl cyclase (sGC) inhibitor ODQ
      and the inhibitor of small conductance Ca2+-activated K+ channels apamin
      prevented relaxation induced by endotoxin, nicotine, exogenous NO (DETA-NONOate),
      and the NO-independent sGC activator BAY 41-2272. NO synthesis was observed in
      neuronal soma, axons, and nerve endings of the myenteric plexus in the fundus of
      endotoxin-treated rats and was prevented by L-NAME, tetrodotoxin, and
      hexamethonium. nNOS and iNOS mRNA and protein contents were unchanged. Our
      findings demonstrate synthesis of NO in post-ganglionic myenteric neurons during
      early endotoxemia that mediates gastric hypo-contractility. The effect of NO is
      mediated via sGC and small conductance Ca2+-activated K+channels.

PMID- 14715699
TI  - Micropatterning of proteins and mammalian cells on biomaterials.
AB  - Controlling the spatial organization of cells is vital in engineering tissues
      that require precisely defined cellular architectures. For example, functional
      nerves or blood vessels form only when groups of cells are organized and aligned
      in very specific geometries. Yet, scaffold designs incorporating spatially
      defined physical cues such as microscale surface topographies or spatial patterns
      of extracellular matrix to guide the spatial organization and behavior of cells
      cultured in vitro remain largely unexplored. Here we demonstrate a new approach
      for controlling the spatial organization, spreading, and orientation of cells on
      two micropatterned biomaterials: chitosan and gelatin. Biomaterials with grooves
      of defined width and depth were fabricated using a two-step soft lithography
      process. Selective attachment and spreading of cells within the grooves was
      ensured by covalently modifying the plateau regions with commercially available
      protein resistant triblock copolymers. Precise spatial control over cell
      spreading and orientation has been observed when human microvascular endothelial
      cells are cultured on these patterned biomaterials, suggesting the potential of
      this technique in creating tissue culture scaffolds with defined chemical and
      topographical features.

PMID- 14715700
TI  - Platelet-activating factor (PAF) induces activation of matrix metalloproteinase 2
      activity and vascular endothelial cell invasion and migration.
AB  - Tumor-induced angiogenic responses lead to complex phenotypic changes in vascular
      endothelial cells, which must coordinate the expression of both proteases and
      protease inhibitors prior to the proliferation and invasion of surrounding
      stroma. Matrix metalloproteinase 2 (MMP2), which degrades Type IV collagen, is
      produced as proMMP2. proMMP2 is activated in part through its interactions with
      membrane Type 1 MMP (MT1-MMP) and tissue inhibitor of matrix metalloproteinase 2
      (TIMP2). In this study, we demonstrate that platelet-activating factor (PAF) is a
      potent inducer of human umbilical vein endothelial cell (HUVEC) migration and
      invasion, which is attenuated by PAF receptor antagonists, and that PAF receptor
      antagonists inhibit the migration and invasion of HUVEC mediated by medium
      conditioned by a prostatic carcinoma cell line. We confirm that PAF receptor
      antagonists inhibit proliferation of HUVEC grown in rich growth medium. We show
      that PAF increases mRNA levels for MT1-MMP and TIMP2, followed by increased
      temporal conversion of latent proMMP2 to MMP2. Finally, we demonstrate that the
      ratio of MT1-MMP to TIMP2 in membrane preparations from PAF-stimulated HUVEC is
      1.6:1, approximating the hypothesized ideal ratio of 2:1 necessary for the
      conversion of proMMP2 to MMP2. Our data support the involvement of PAF in
      vascular endothelial cell migration and invasion.

PMID- 14715701
TI  - Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human
      monocytes and in the human monocytic cell line U937: possible implications for
      peri-operative plaque instability.
AB  - Plaque destabilization leading to myocardial infarction is observed after surgery
      even if the intervention is of noncardiovascular nature. Mediators of peri- or
      postoperative stress responsible for such events could include catecholamines and
      lipopolysaccharide (LPS). Monocytes may be involved in destabilization of
      atherosclerotic plaques by production of matrix metalloproteinases (MMP). We
      examined whether catecholamines could affect the expression of MMPs in human
      monocytes/macrophages and whether catecholamines could modulate LPS-stimulated
      expression of particular MMPs in these cells. Epinephrine and norepinephrine up
      regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral
      blood monocytes and monocyte-derived macrophages. We further characterized this
      effect employing the monocytic cell line U937 and showed that catecholamines
      potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA
      levels of the respective MMPs also increased. These effects did not result from
      higher mRNA stability but rather from increased transcription possibly induced by
      enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2
      receptors. If this mechanism is also effective in vivo, our findings might, at
      least in part, help to explain the observation that cardiac events are important
      causes of morbidity and mortality after noncardiac surgery and support the
      findings that peri-operative beta-blockade has been shown to reduce postoperative
      mortality from cardiac events.

PMID- 14715702
TI  - Skeletal muscle gene expression in space-flown rats.
AB  - Skeletal muscles are vulnerable to marked atrophy under microgravity. This
      phenomenon is due to the transcriptional alteration of skeletal muscle cells to
      weightlessness. To further investigate this issue at a subcellular level, we
      examined the expression of approximately 26,000 gastrocnemius muscle genes in
      space-flown rats by DNA microarray analysis. Comparison of the changes in gene
      expression among spaceflight, tail-suspended, and denervated rats revealed that
      such changes were unique after spaceflight and not just an extension of simulated
      weightlessness. The microarray data showed two spaceflight-specific gene
      expression patterns: 1) imbalanced expression of mitochondrial genes with
      disturbed expression of cytoskeletal molecules, including putative mitochondria
      anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up
      regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which
      are rate-limiting enzymes of muscle protein degradation. Distorted expression of
      cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria
      in the cell. Several oxidative stress-inducible genes were highly expressed in
      the muscle of spaceflight rats. We postulate that mitochondrial dislocation
      during spaceflight has deleterious effects on muscle fibers, leading to atrophy
      in the form of insufficient energy provision for construction and leakage of
      reactive oxygen species from the mitochondria.

PMID- 14715703
TI  - The metabolism of phospholipids oscillates rhythmically in cultures of
      fibroblasts and is regulated by the clock protein PERIOD 1.
AB  - The mammalian circadian timing system is composed of countless cell oscillators
      distributed throughout the body and central pacemakers regulating temporal
      physiology and behavior. Peripheral clocks display circadian rhythms in gene
      expression both in vivo and in culture. We examined the biosynthesis of
      phospholipids as well as the expression of the clock gene period 1 (Per1) and its
      potential involvement in the regulation of the phospholipid metabolism in
      cultured quiescent NIH 3T3 cells synchronized by a 2 h serum shock. A 30 min
      pulse of radiolabeled precursor was given at phases ranging from 0.5 to 62 h
      after serum treatment. We observed a daily rhythm in the phospholipid labeling
      that persisted at least for two cycles, with levels significantly decreasing 29
      and 58 h after treatment. Per1 expression exhibited a rapid and transient
      induction and a daily rhythmicity in antiphase to the lipid labeling. After Per1
      expression knockdown, the rhythm of phospholipid labeling was lost. Furthermore,
      in cultures of CLOCK mutant fibroblasts--cells with a clock mechanism impairment-
      PER1 was equally expressed at all times examined and the phospholipid labeling
      did not oscillate. The results demonstrate that the biosynthesis of phospholipids
      oscillates daily in cultured fibroblasts by an endogenous clock mechanism
      involving Per1 expression.

PMID- 14715704
TI  - Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin
      fluorophore A2-E may contribute to the pathogenesis of age-related macular
      degeneration.
AB  - Lipofuscin accumulation in the retinal pigment epithelium (RPE) is associated
      with various blinding retinal diseases, including age-related macular
      degeneration (AMD). The major lipofuscin fluorophor A2-E is thought to play an
      important pathogenetic role. In previous studies A2-E was shown to severely
      impair lysosomal function of RPE cells. However, the underlying molecular
      mechanism remained obscure. Using purified lysosomes from RPE cells we now
      demonstrate that A2-E is a potent inhibitor of the ATP-driven proton pump located
      in the lysosomal membrane. Such inhibition of proton transport to the lysosomal
      lumen results in an increase of the lysosomal pH with subsequent inhibition of
      lysosomal hydrolases. An essential task of the lysosomal apparatus of postmitotic
      RPE for normal photoreceptor function is phagocytosis and degradation of
      membranous discs shed from photoreceptor outer segments (POS) and of biomolecules
      from autophagy. When the lysosomes of cultured RPE cells were experimentally
      loaded with A2-E, we observed intracellular accumulation of exogenously added POS
      with subsequent congestion of the phagocytic process. Moreover, the autophagic
      sequestration of cytoplasmic material was also markedly reduced after A2-E
      loading. These data support the hypothesis that A2-E-induced lysosomal
      dysfunction contributes to the pathogenesis of AMD and other retinal diseases
      associated with excessive lipofuscin accumulation.

PMID- 14715705
TI  - Genes differentially expressed in thyroid carcinoma identified by comparison of
      SAGE expression profiles.
AB  - To identify transcripts that distinguish malignant from benign thyroid disease
      serial analysis of gene expression (SAGE) profiles of papillary thyroid carcinoma
      and of normal thyroid are compared. Of the 21,000 tags analyzed, 204 tags are
      differentially expressed with statistical significance in the tumor. Thyroid
      tumor specificity of these transcripts is determined in silico using the tissue
      preferential expression (TPE) algorithm. TPE values demonstrate that 42 tags of
      the 204 are thyroid tumor specific. BC013035, a cDNA encoding a novel protein, is
      up-regulated from 0 to 24 tags in the thyroid tumor SAGE library. In a tissue
      panel of 30 thyroid tumors and 12 controls, it has an expression pattern similar
      to thyroid peroxidase, indicating possible involvement of BC013035 in thyroid
      differentiation. A tag coding for extracellular matrix protein 1 (ECM1) is absent
      in the normal thyroid SAGE library and present 55 times in the tumor. ECM1, a
      protein recently associated with angiogenesis and expressed in metastatic breast
      carcinoma, is up-regulated in 50% of all thyroid carcinoma and absent in normal
      controls and follicular adenoma. In conclusion, SAGE analysis and subsequent
      determination of TPE values facilitates the rapid distinction of genes
      specifically expressed in cancer tissues.

PMID- 14715706
TI  - Interaction between 3' untranslated region of calcitonin receptor messenger
      ribonucleic acid (RNA) and adenylate/uridylate (AU)-rich element binding proteins
      (AU-rich RNA-binding factor 1 and Hu antigen R).
AB  - Our previous results in mouse osteoclasts suggested that calcitonin (CT) alters
      CT receptor (CTR) mRNA stability. The CTR mRNA transcript contains several
      adenylate/uridylate (AU)-rich destabilizing elements in the 3' untranslated
      region (3'UTR). When the 3'UTR of mouse CTR mRNA was labeled by [alpha-(32)P]
      uridine 5-triphosphate, interactions were observed between the transcript and
      several cell extracts, including those from the osteoclast progenitor
      monocyte/macrophage cell line, RAW 264.7. The molecular masses of the interacting
      proteins ranged from approximately 35 to 50 kDa, similar to AU-rich RNA-binding
      factor 1 (AUF1) and Hu antigen R (HuR). Radiolabeled 3'UTR transcripts bound with
      a 40-kDa protein, which could be extracted from cells transfected with AUF1 p40.
      To confirm the binding specificity, a pSG5 vector construct, containing the AUF1
      p40 with an hemagglutinin tag, was transiently transfected into NIH3T3 cells. The
      extracts were incubated with poly(A)-added CTR3'UTR. The reaction mixture was
      immunoprecipitated using an antihemagglutinin antibody and precipitated mRNA
      species were extracted and reverse transcribed using oligo-dT primers. It was
      found that PCR primers specific for the 3'UTR of CTR mRNA sequence generated a
      PCR signal. No signal was observed when mutated AUF1 p40 was transfected. In a
      manner similar to the AUF1 binding, HuR was also found to bind to the 3'UTR.
      Specific binding of AUF1 p40 and HuR was also found with RNA extracted from mouse
      osteoclasts. Treatment of osteoclasts with CT did not significantly affect the
      expression of AUF1 but decreased the levels of HuR and its mRNA. The role of
      CTR3'UTR in mRNA stability was further tested by expressing luciferase reporter
      constructs that did, or did not, contain the CTR3'UTR, under the control of the
      tetracycline-regulatory system. The results showed that the addition of 3'UTR
      considerably shortened the mRNA half-life of the luciferase reporter gene. These
      results suggest that AUF1 p40, HuR, and the 3'UTR of the CTR mRNA transcript
      could be involved in posttranscriptional regulation of CTR mRNA expression.

PMID- 14715707
TI  - Transcriptional regulation of the human chorionic gonadotropin beta gene during
      villous trophoblast differentiation.
AB  - Expression of the trophoblast-specific subunit of human chorionic gonadotropin,
      CGbeta, is associated with fusion of cytotrophoblasts into a multinuclear
      syncytium. Here, we studied regulation of the CGbeta5 gene in trophoblasts
      undergoing in vitro syncytialization. Transfection of luciferase reporters
      harboring different lengths of the CGbeta5 upstream sequence revealed that the
      proximal promoter region (-345 to +114) is sufficient to govern differentiation
      dependent induction. Mutational analyses suggested that two selective promoter
      factor (Sp) and three activating protein 2 (AP-2) recognition sequences are
      necessary for full activity of the promoter. During syncytialization these
      elements interacted with increasing amounts of the transcription factors Sp1,
      Sp3, and AP-2alpha in electrophoretic mobility shift assay, but only AP-2alpha
      binding rose upon elevation of cAMP levels with forskolin. Increasing expression
      of different isoforms of Sp1 and Sp3 could also be detected by Western blot
      analyses. Sp1/Sp3 localized to syncytial nuclei both in differentiated cultures
      and in term placental tissue, suggesting assembly of functional transcriptional
      complexes. Costaining of the transcription factors with E-cadherin on term
      placental sections revealed that 47 and 33% of cytotrophoblast nuclei were
      negative for Sp1 and Sp3, respectively. In contrast, immunohistochemistry of
      early tissue demonstrated expression of Sp1 in the majority of cyto- and
      syncytiotrophoblasts, whereas Sp3 was absent from the syncytium. Sp1 and Sp3
      induced wild-type/mutant promoter constructs upon transfection in Sp-deficient SL
      2 cells, indicating that the Sp elements function as activating sequences. The
      data suggest that increasing concentrations of Sp1, Sp3, and AP-2alpha enhance
      transcription of CGbeta in differentiating term trophoblasts, whereas a different
      combination of factors may control expression in early placentas.

PMID- 14715708
TI  - Different modes of gonadotropin-releasing hormone (GnRH) release from multiple
      GnRH systems as revealed by radioimmunoassay using brain slices of a teleost, the
      dwarf gourami (Colisa lalia).
AB  - It has become a general notion that there are multiple GnRH systems in the
      vertebrate brains. To measure GnRH release activities from different GnRH
      systems, we conducted a static incubation of brain-pituitary slices under various
      conditions, and GnRH released into the incubation medium was measured by RIA. The
      slices were divided into two parts, one containing GnRH neurons in the preoptic
      area and axon terminals in the pituitary (POA-GnRH slices), and the other
      containing the cell bodies and fibers of terminal nerve-GnRH neurons and midbrain
      tegmentum-GnRH neurons (TN-TEG-GnRH slices). We demonstrated that GnRH release
      was evoked by high [K(+)](o) depolarizing stimuli (in both POA-GnRH and TN-TEG
      GnRH slices) via Ca(2+) influx through voltage-gated Ca(2+) channels. The most
      prominent result was the presence of conspicuous sexual difference in the amount
      of GnRH release in the POA-GnRH slices. The GnRH release from TN-TEG-GnRH slices
      also showed a small sexual difference, which was by far more inconspicuous than
      that of POA-GnRH slices. Immunohistochemical analysis using an antiserum specific
      to the seabream GnRH (sbGnRH; suggested to be specific to POA-GnRH neurons)
      revealed the presence of a much larger number of POA-GnRH neurons in males than
      in females. This clear morphological sexual difference is suggested to underlie
      that of GnRH release in the POA-GnRH slices.

PMID- 14715709
TI  - Steroidogenic acute regulatory (StAR)-directed immunotherapy protects against
      tumor growth of StAR-expressing Sp2-0 cells in a rodent adrenocortical carcinoma
      model.
AB  - Adrenocortical carcinoma (ACC) is a highly malignant tumor with poor response to
      classical antitumor therapy. Steroidogenic acute regulatory (StAR) protein is
      expressed in most human ACCs. The aim of this study was to induce antitumoral T
      cells directed against StAR in a murine tumor model. Because a suitable syngenic
      adrenocortical mouse tumor model is lacking, we established a clone of the mouse
      myeloma Sp2-0 tumor cell line stably expressing murine StAR (Sp2-mStAR). Using
      repeated im injections of plasmid DNA encoding mStAR followed by infection with a
      recombinant vaccinia virus (rVV) expressing mStAR, we induced a cytotoxic T-cell
      response as measured by enzyme-linked immunospot assay. To demonstrate antitumor
      activity of the vaccination procedure, mice were treated as follows: group A,
      mice immunized with plasmids and rVV encoding mStAR receiving Sp2-mStAR cells;
      control group B, mice immunized with the empty plasmid and the empty rVV
      receiving Sp2-mStAR cells; control group C, mice immunized with the empty plasmid
      and rVV encoding P450 side-chain cleavage enzyme receiving Sp2-mStAR cells; and
      control group D, mice immunized with plasmid and rVV encoding mStAR receiving
      parental Sp2-0 cells. A high proportion (89-100%) of the control groups B, C, and
      D developed subcutaneous tumors. In contrast, immunization specific for mStAR
      (group A) was highly protective against tumor growth (percentage of tumor-free
      animals, 67%; P < 0.001 vs. controls). In summary, these results show that T-cell
      tolerance toward mStAR can be broken, resulting in antitumoral immunity. Thus,
      StAR represents a candidate target antigen for immunotherapeutic strategies
      against ACC.

PMID- 14715710
TI  - Molten globule structure and steroidogenic activity of N-218 MLN64 in human
      placental mitochondria.
AB  - Progesterone synthesis by the human placenta requires the conversion of
      mitochondrial cholesterol to pregnenolone by cytochrome P450scc. Most
      steroidogenic tissues use the steroidogenic acute regulatory protein (StAR) to
      deliver cholesterol to the inner mitochondrial membrane where P450scc is located,
      but StAR is not expressed in the human placenta. However, the human placenta does
      express MLN64, which has a C-terminal domain homologous to StAR that can also
      transport cholesterol. We investigated the ability of bacterially expressed N-218
      MLN64 and N-62 StAR to transport cholesterol between artificial membranes and to
      its inner membrane site of use in placental mitochondria. Urea denaturation
      experiments show that N-218 MLN64 undergoes a pH-dependent and denaturant
      dependent structural transition to a molten globule state, as reported previously
      for N-62 StAR. N-218 MLN64 stimulated cholesterol transfer between artificial
      phospholipid vesicles with an initial rate of 6.5 mol/min.mol N-218 MLN64. Both N
      218 MLN64 and N-62 StAR stimulated cholesterol transfer to the inner
      mitochondrial membrane, as evidenced by a 6-fold stimulation of pregnenolone
      synthesis with saturating transporter. This stimulation was seen only after the
      endogenous cholesterol in the steroidogenic pool of the isolated mitochondria was
      first depleted. No stimulation was observed by N-218 MLN64 or N-62 StAR when
      20alpha-hydroxycholesterol was added as substrate for P450scc, confirming that
      these proteins stimulate P450scc activity by enhancing cholesterol transport.
      MLN64 levels in placental JEG-3 cells were unresponsive to stimulation by 8-bromo
      cAMP over 24 h. These data show that human N-218 MLN64 and N-62 StAR have similar
      biophysical and functional properties and are able to stimulate steroidogenesis
      in a human placental system, which normally lacks StAR. The results reveal that
      with saturating MLN64, steroidogenesis by placental mitochondria proceeds at near
      maximal rate.

PMID- 14715711
TI  - Leptin increases cardiomyocyte hyperplasia via extracellular signal-regulated
      kinase- and phosphatidylinositol 3-kinase-dependent signaling pathways.
AB  - Obesity is a major risk factor for the development of heart failure. Importantly,
      it is now appreciated that a change in the number of myocytes is one of multiple
      structural and functional alterations (remodeling) leading to heart failure. Here
      we investigate the effect of leptin, the product of the obese (ob) gene, on
      proliferation of human and murine cardiomyocytes. Leptin caused a time- and dose
      dependent significant increase in proliferation of HL-1 cells that was inhibited
      by preincubation with PD98059 and LY294002, suggesting that leptin mediated
      proliferation via extracellular signal-regulated kinase-1/2- and
      phosphatidylinositol-3-kinase-dependent signaling pathways. We confirmed that
      leptin activates both extracellular signal-regulated kinase-1/2 phosphorylation
      and association of phosphatidylinositol-3-kinase (regulatory p85 subunit) with
      phosphotyrosine immunoprecipitates. We also examined bromodeoxyuridine
      incorporation as a measure of new DNA synthesis and demonstrated a stimulatory
      effect of leptin in both HL-1 cells and human cardiomyocytes. Bromodeoxyuridine
      incorporation in HL-1 cells was inhibited by PD98059 and LY294002. Our results
      establish a mitogenic effect of leptin in cardiomyocytes and provide additional
      evidence for a potential direct link between leptin and cardiac remodeling in
      obesity.

PMID- 14715712
TI  - The skeletal effects of glucocorticoid excess override those of orchidectomy in
      mice.
AB  - Hypogonadism has been implicated as a contributing factor in glucocorticoid
      induced osteoporosis, but evidence for this is limited. Hypogonadism and
      glucocorticoid excess both cause bone loss, but the cellular mechanisms
      responsible are distinct. Loss of gonadal steroids causes an increase in bone
      remodeling by up-regulating osteoblastogenesis and osteoclastogenesis.
      Glucocorticoid excess, conversely, suppresses remodeling by down-regulating
      osteoblastogenesis and osteoclastogenesis. Nonetheless, both conditions increase
      osteoblast apoptosis and decrease osteoclast apoptosis, and both cause bone loss
      due to an undersupply of osteoblasts relative to the need for cavity repair. To
      investigate their interactions, we compared the effects of orchidectomy,
      glucocorticoid excess, or both combined in mice. After 28 d, serum unbound
      testosterone concentration and seminal vesicle weight were not diminished when
      prednisolone was administered alone. Vertebral bone mineral density and
      compression strength decreased to the same extent in animals receiving
      prednisolone or after orchidectomy, but the changes were not additive.
      Orchidectomy induced the expected up-regulation of osteoblast and osteoclast
      progenitors, but these changes were prevented in orchidectomized mice
      simultaneously receiving glucocorticoids. Likewise, the increase in cancellous
      osteoid, osteoblasts, osteoclasts, bone formation, and activation frequency
      caused by orchidectomy were prevented by prednisolone. The prevalence of
      osteoblast apoptosis increased in the mice receiving prednisolone or after
      orchidectomy, but the increases were not additive. These data demonstrate that
      hypogonadism does not occur in or contribute to glucocorticoid-induced
      osteoporosis and that the adverse skeletal effects of glucocorticoid excess
      override those of orchidectomy.

PMID- 14715713
TI  - Differential modulation of energy balance by leptin, ciliary neurotrophic factor,
      and leukemia inhibitory factor gene delivery: microarray deoxyribonucleic acid
      chip analysis of gene expression.
AB  - Most obese animal models, whether associated with genetic, diet-induced, or age
      related obesity, display pronounced leptin resistance, rendering leptin
      supplement therapy ineffective in treating obesity. Ciliary neurotrophic factor
      (CNTF) has been recently used to invoke leptin-like signaling pathways, thereby
      circumventing leptin resistance. In the current study, we characterize immediate
      and long-term molecular events in the hypothalamus of rats exposed to the
      sustained ectopic expression of leptin, CNTF, or leukemia inhibitory factor,
      another neurocytokine of IL-6 family, all delivered centrally via a viral vector.
      The respective transgene-encoded ligands induced similar but not identical
      metabolic responses as assessed by the reduction in body weight gain and changes
      in food intake. To define molecular mechanisms of weight-reducing and
      anorexigenic action of cytokines, we have analyzed the gene expression profiles
      of 1300 brain-specific genes in the hypothalami of normal rats subjected to the
      prolonged cytokine action for 10 wk. We present evidence that constitutive
      expression of cytokines in the brain induces changes in gene expression
      characteristic of chronic inflammation leading to either temporal weight
      reduction (CNTF) or severe cachexia (leukemia inhibitory factor). Our results
      convey a cautionary note regarding potential use of the tested cytokines in
      therapeutic applications.

PMID- 14715714
TI  - Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow
      adipocytes, but maintain normal bone formation.
AB  - Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the
      skeleton. The cellular activity of GCs is regulated at a prereceptor level by
      11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which
      predominates in bone, functions as a reductase in intact cells and regenerates
      active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of
      the present study was to investigate the role of this intracrine activation of
      GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/
      )). The HSD1(-/-) mice exhibited no significant changes in cortical or trabecular
      bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age
      related bone loss similar to that observed in Wt mice. Histomorphometric analysis
      showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt
      mice. However, examination of bone marrow composition revealed a total absence of
      marrow adipocytes in HSD1(-/-) mice. Cells from Wt and HSD1(-/-) mice exhibited
      similar growth rates as well as similar levels of production of osteoblastic
      markers. The adipocyte-forming capacity of in vitro cultured bone marrow stromal
      cells and trabecular osteoblasts was similar in HSD1(-/-) and Wt mice. In
      conclusion, our results suggest that 11betaHSD1 amplification of intracellular GC
      actions in mice may be required for bone marrow adipocyte formation, but not for
      bone formation. The clinical relevance of this observation remains to be
      determined.

PMID- 14715715
TI  - Deficits in reproduction and pro-gonadotropin-releasing hormone processing in
      male Cpefat mice.
AB  - Cpe(fat/fat) mice are obese, diabetic, and infertile. These animals have a point
      mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal
      basic amino acids from peptide intermediates. The mutation renders the enzyme
      unstable, and it is rapidly degraded. Although the infertility of Cpe(fat/fat)
      mice has not been systematically investigated, it is thought to be due to a
      deficit in GnRH processing. We have evaluated this hypothesis and found
      hypothalamic GnRH levels to be reduced by 65-78% and concentrations of pro-GnRH
      and C-terminal-extended intermediates to be high. Basal serum gonadotropin
      contents are similar among wild-type, heterozygous, and homozygous mice. Testis
      morphology and function are abnormal in older obese Cpe(fat/fat) mice. Matings
      between homozygous mutants yield a 5% pregnancy rate. By comparison, when 50-d
      old Cpe(fat/fat) males are paired with heterozygous females, rates increase to
      43%, and they rapidly decrease to negligible levels by 120 d. As fertility
      declines without accompanying changes in the hypothalamic-pituitary-gonadal axis
      and before obesity is evident, reproduction is more complex than originally
      thought. This suspicion is confirmed in 90-d-old Cpe(fat/fat) males, who readily
      interact with females, but rarely mount and fail to show intromission or
      ejaculation behaviors. Together, these findings show that CPE is a key enzyme for
      pro-GnRH processing in vivo; however, the reproductive deficits in Cpe(fat/fat)
      males appear to be due primarily to abnormal sexual behavior.

PMID- 14715716
TI  - Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting
      in the brain of rat.
AB  - Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful
      conditions, a rapid and transient increase in circulating prolactin (PRL) is
      observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid
      plexus of rat brain. In this study we used restraint stress in water to elucidate
      the mechanism by which PRLR in the rat brain mediate the protective effect of PRL
      against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts
      through the long form of PRLR in the hypothalamus. This is followed by an
      increase in the long form of PRLR mRNA expression in the choroid plexus of the
      brain, which provides protection against restraint stress in water-induced
      hypocalcemia and gastric erosions. We also show that PRL induces the expression
      of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular
      nucleus. These results suggest that the PRL levels increase in response to
      stress, and it moves from the circulation to the cerebrospinal fluid to act on
      the central nervous system and thereby plays an important role in helping to
      protect against acute stress-induced hypocalcemia and gastric erosions.

PMID- 14715717
TI  - Insulin-like growth factor-binding protein-3 in porcine ovarian granulosa cells:
      gene cloning, promoter mapping, and follicle-stimulating hormone regulation.
AB  - The role and regulation of IGF-binding protein-3 (IGFBP-3) in the ovary is not
      fully understood. We cloned and determined the sequence of 12,257 bp of the pig
      IGFBP-3 gene that includes 4,296 bp of the flanking promoter sequence. The
      porcine IGFBP-3 promoter sequence shares two highly conserved regions with the
      human and bovine IGFBP-3 promoters and a mouse DNA clone. The first is a 38 bp
      region between -1095 and -1058, whereas the second is a 73-bp region between -63
      and +10 of the pig sequence. Projected translation of the open reading frame of
      our sequence gave a peptide sequence identical to that determined by peptide
      sequencing, but with 27 additional amino acids upstream of this sequence and is
      highly similar to the human, bovine, rat, and mouse IGFBP-3 peptides. Using RT
      PCR we demonstrated that FSH regulates IGFBP-3 mRNA expression in a biphasic
      manner, with an early induction (maximal at 3 h) and an inhibition at 24 h after
      FSH treatment. The inhibition at 24 h was not due to changes in IGFBP-3 mRNA
      stability. A similar pattern of FSH modulation of the IGFBP-3 gene transcription
      was demonstrated by the reporter activity of granulosa cells transiently
      transfected with IGFBP-3 promoter constructs. The site for FSH stimulation of the
      IGFBP-3 gene was localized to the sequence between -61 and -48 relative to the
      transcription start site. Regulation of IGFBP-3 transcription by FSH suggests a
      role for IGFBP-3 in follicular development that may be independent of IGF-I.

PMID- 14715718
TI  - Comparison of responses of primate spinothalamic tract neurons to pruritic and
      algogenic stimuli.
AB  - We investigated the role of mechanosensitive spinothalamic tract (STT) neurons in
      mediating 1) the itch evoked by intradermal injection of histamine, 2) the
      enhanced sense of itch evoked by innocuous stroking (alloknesis), and 3) the
      enhanced pain evoked by punctate stimulation (hyperalgesia) of the skin
      surrounding the injection site. Responses to intradermal injections of histamine
      and capsaicin were compared in STT neurons recorded in either the superficial or
      the deep dorsal horn of the anesthetized monkey. Each neuron was identified by
      antidromic activation from the ventral posterior lateral nucleus of thalamus and
      classified by its initial responses to mechanical stimuli as wide dynamic range
      (WDR) or high-threshold (HT). Approximately half of the WDRs and one of the HTs
      responded weakly to histamine, some with a duration > 5 min, the maximal time
      allotted. WDRs but not HTs exhibited a significant increase in response to
      punctate stimulation after histamine consistent with their possible role in
      mediating histamine-induced hyperalgesia. Neither type of neuron exhibited
      significant changes in response to stroking, consistent with their unlikely role
      in mediating alloknesis. Furthermore, nearly all STT neurons exhibited vigorous
      and persistent responses to capsaicin, after which they became sensitized to
      stroking and to punctate stimulation. We conclude that the STT neurons in our
      sample are more likely to contribute to pain, allodynia, and hyperalgesia than to
      itch and alloknesis.

PMID- 14715720
TI  - Mechanism of irregular firing of suprachiasmatic nucleus neurons in rat
      hypothalamic slices.
AB  - The mechanisms of irregular firing of spontaneous action potentials in neurons
      from the rat suprachiasmatic nucleus (SCN) were studied in hypothalamic slices
      using cell-attached and whole cell recording. The firing pattern of spontaneous
      action potentials could be divided into regular and irregular, based on the
      interspike interval (ISI) histogram and the membrane potential trajectory between
      action potentials. Similar to previous studies, regular neurons had a firing rate
      about >3.5 Hz and irregular neurons typically fired about <3.5 Hz. The ISI of
      irregular-firing neurons was a linear function of the sum of inhibitory
      postsynaptic potentials (IPSPs) between action potentials. Bicuculline (10-30
      microM) suppressed IPSPs and converted an irregular pattern to a more regular
      firing. Bicuculline also depolarized SCN neurons and induced bursting-like
      activity in some SCN neurons. Gabazine (20 microM), however, suppressed IPSPs
      without depolarization, and also converted irregular activity to regular firing.
      Thus GABAA receptor-mediated IPSPs appear responsible for irregular firing of SCN
      neurons in hypothalamic slices.

PMID- 14715719
TI  - Novel form of LTD induced by transient, partial inhibition of the Na,K-pump in
      rat hippocampal CA1 cells.
AB  - We tested the hypothesis that transient, partial inhibition of the Na,K-pumps
      could produce lasting effects on synaptic efficacy in brain tissue by applying a
      low concentration of the ouabain analogue, dihydroouabain (DHO), to hippocampal
      slices for 15 min and studying the effects on field excitatory postsynaptic
      potentials (fEPSPs). DHO caused a suppression of fEPSPs during the application
      period, but this recovered only partially, to approximately 80% of control
      levels, after washout lasting as long as 2 h. The lasting suppression had several
      properties in common with low-frequency stimulation induced long-term depression
      (LFS-LTD), including an ability to depotentiate long-term potentiated responses.
      However, DHO-LTD was insensitive to blockade of N-methyl-d-aspartate or mGlu
      receptors or to inhibitors of protein kinase C or p38 MAP kinase. DHO-LTD did not
      co-occlude with LFS-LTD and therefore appears to represent a novel form of LTD.
      Interestingly, DHO-LTD could be prevented by pretreating slices with iberiotoxin,
      the selective blocker of large, Ca(2+)-dependent K+ channels ("big K," BK
      channels), although this toxin did not affect basal fEPSPs. Certain pathological
      conditions, including hypoxia and ischemia, are associated with a decrease in
      Na,K-pump activity and hence DHO-LTD may serve as a model for the effects on
      neuronal function in these conditions.

PMID- 14715721
TI  - Neuronal correlates of face identification in the monkey anterior temporal
      cortical areas.
AB  - To investigate the neuronal basis underlying face identification, the activity of
      face neurons in the anterior superior temporal sulcus (STS) and the anterior
      inferior temporal gyrus (ITG) of macaque monkeys was analyzed during their
      performance of a face-identification task. The face space was composed by the
      activities of face neurons during the face-identification task, based on a
      multidimensional scaling (MDS) method; the face space composed by the anterior
      STS neurons represented facial views, whereas that composed by the anterior ITG
      neurons represented facial identity. The temporal correlation between the
      behavioral reaction time of the animal and the latency of face-related neuronal
      responses was also analyzed. The response latency of some of the face neurons in
      the anterior ITG exhibited a significant correlation with the behavioral reaction
      time, whereas this correlation was not significant in the anterior STS. The
      correlation of the latency of face-related neuronal responses in the anterior ITG
      with the behavioral reaction time was not found to be attributed to the
      correlation between the response latency and the magnitude of the neuronal
      responses. The present results suggest that the anterior ITG is closely related
      to judgments of facial identity, and that the anterior STS is closely related to
      analyses of incoming perceptual information; face identification in monkeys might
      involve interactions between the two areas.

PMID- 14715722
TI  - CNS activation by noxious heat to the hand or foot: site-dependent delay in
      sensory but not emotion circuitry.
AB  - Recently, functional magnetic resonance imaging has been used as a novel method
      of evaluating the CNS response to noxious stimuli. In a previous study, a
      prolonged noxious thermal stimulus applied to the dorsum of the hand produced
      more than one hemodynamic response that was temporally segregated. The two major
      responses displayed activation in primary sensory regions (classic pain
      circuitry) and regions involved in emotion (reward/aversion circuitry),
      respectively. In the current study, we applied the same thermal stimulus
      separately to the dorsum of the left foot and the dorsum of the left hand in the
      same subjects and compared the hemodynamic responses to evaluate the effects of
      conduction distance on CNS activation within these two segregated systems. After
      stimulus delivery to the foot, the hemodynamic response in primary sensory
      networks occurs after a delay of 3.6 +/- 1.3 s as compared with the response
      after hand stimulation. The relative delay of the hemodynamic response in
      reward/aversion regions is not significantly different between hand and foot
      stimulation (0.6 +/- 2.1 s). These results within the primary sensory system are
      consistent with the greater conduction distance of the peripheral nerves from the
      hand versus the foot. The observation that the response within the
      reward/aversion pathways occurs with the same rapid temporal characteristics
      after either hand or foot stimulation supports the notion that the circuitry
      involved in the evaluation of aversive stimuli is rapid in onset and probably
      represents a major protective mechanism for survival.

PMID- 14715723
TI  - Reality of developing a community-wide antibiogram.

PMID- 14715724
TI  - Identification and susceptibility testing of Enterobacteriaceae and Pseudomonas
      aeruginosa by direct inoculation from positive BACTEC blood culture bottles into
      Vitek 2.
AB  - Inoculation of an automated system for rapid identification (ID) and
      antimicrobial susceptibility testing (AST) directly from positive blood culture
      bottles will reduce the turnaround time of laboratory diagnosis of septicemic
      patients, which benefits clinical outcome and decreases patient costs. Direct
      test results, however, must always be confirmed by testing a pure overnight
      culture, which is the "gold standard." We studied the accuracy of direct testing
      versus repeat testing in order to investigate the possibility of refraining from
      repeat testing. We also assessed the clinical risk of reporting results based on
      direct testing only. We inoculated Vitek 2 (bioMerieux) directly from 410
      positive BACTEC 9240 (BD) blood culture bottles containing gram-negative rods and
      studied the ID and AST results. In a comparison of direct inoculation with the
      standard method, a total of 344 isolates of Enterobacteriaceae and Pseudomonas
      aeruginosa were tested, and 93.0% were correctly identified. Of the 39 (10.2%)
      samples that contained bacilli not identifiable by Vitek 2, only 1 gave a
      conclusive, correct result. The overall MIC agreement among 312 isolates was
      99.2%, with 0.8% very major and 0.02% major error rates. Of only three
      (polymicrobial) samples, the direct susceptibility pattern would be reported to
      the clinician as too sensitive. Vitek 2 results obtained from direct inoculation
      of blood culture bottles containing gram-negative bacilli are safe enough for
      immediate reporting, provided that ID and AST are consistent. Repeat testing is
      not necessary, unless Gram stain or overnight subculture results raise doubt
      about the purity of the culture.

PMID- 14715725
TI  - Utility of the focus technologies west nile virus immunoglobulin M capture enzyme
      linked immunosorbent assay for testing cerebrospinal fluid.
AB  - Focus Technologies has developed an immunoglobulin M (IgM) capture enzyme-linked
      immunosorbent assay (ELISA) kit that utilizes recombinant West Nile virus (WNV)
      antigens to detect WNV IgM in serum. We evaluate here the utility of the kit for
      detecting WNV IgM in cerebrospinal fluid (CSF). The sensitivity was evaluated by
      using 52 CSF specimens from the 2002 WNV season that were positive in both the
      Public Health Service Laboratories WNV IgM ELISA and an in-house WNV IgM ELISA
      with native WNV antigen. The specificity was evaluated with two groups of
      specimens: (i). 73 CSF specimens submitted for in-house WNV IgM ELISA testing
      from February through April 2003 and yielding a negative WNV IgM result and (ii).
      60 CSF specimens determined to be positive for another virus by PCR testing.
      Using these 185 CSF specimens at a screening dilution of 1:2, the kit was
      determined to be 100% sensitive and 100% specific. Endpoint titers were
      determined for 20 IgM-positive CSF specimens by testing serial twofold dilutions
      and ranged from 1:8 to 1:512. Index values (specimen absorbance value/calibrator
      absorbance value) for the screening dilution (1:2) showed no correlation with IgM
      titers, whereas index values for higher dilutions showed significant correlation
      with IgM titers. CSF screening dilutions of greater than 1:2 are not recommended,
      however, due to the risk of obtaining false-negative results. These findings show
      that the Focus Technologies WNV IgM capture ELISA, when utilized as recommended,
      offers accurate qualitative detection of WNV IgM in CSF specimens.

PMID- 14715726
TI  - Simple DNA extraction method for dried blood spots and comparison of two PCR
      assays for diagnosis of vertical human immunodeficiency virus type 1 transmission
      in Rwanda.
AB  - Dried blood spots (DBS) on filter paper facilitate the collection, transport, and
      storage of blood samples for laboratory use. A rapid and simple DNA extraction
      procedure from DBS was developed and evaluated for the diagnosis of human
      immunodeficiency virus type 1 (HIV-1) infection in children by an in-house nested
      PCR assay on three genome regions and by the Amplicor HIV-1 DNA prototype assay
      version 1.5 (Roche Molecular Systems). A total of 150 samples from children born
      to HIV-1-infected mothers were collected in Kigali, Rwanda, in parallel as DBS
      and as peripheral blood mononuclear cell (PBMC) pellets. The results obtained on
      DBS by the two PCR assays were compared to the results of nested PCR on PBMCs. Of
      150 PBMC samples, 10 were positive, 117 were negative, and 23 were indeterminate
      for HIV-1 infection. In DNA extracted from filter papers and amplified by using
      the in-house nested PCR, 9 of these 10 positive samples (90%) were found to be
      positive, and 1 was found to be indeterminate (only the pol region could be
      amplified). All of the negative samples and all of the 23 indeterminate samples
      tested negative for HIV-1 infection. When we used the Amplicor DNA test on DBS,
      all of the 10 PBMC-positive samples were found to be positive and all of the 23
      indeterminate samples were found to be negative. Of the PBMC-negative samples,
      115 were found to be negative and 2 were found to be indeterminate. We conclude
      that this simple rapid DNA extraction method on DBS in combination with both
      detection methods gave a reliable molecular diagnosis of HIV-1 infection in
      children born to HIV-infected mothers.

PMID- 14715727
TI  - Multicenter evaluation of a new, automated enzyme-linked immunoassay for
      detection of human immunodeficiency virus-specific antibodies and antigen.
AB  - A collaborative multicenter study was conducted to evaluate the sensitivity,
      specificity, and precision of a three-step, fully automated, qualitative
      microparticle-based enzyme-linked immunoassay (AxSYM HIV Ag/Ab Combo; Abbott
      Laboratories), designed to simultaneously detect (i). antibodies against human
      immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) and (ii). HIV p24
      antigen. A significant reduction in the HIV seroconversion window was achieved by
      combining detection of HIV antibodies and antigen into a single assay format. For
      22 selected, commercial HIV seroconversion panels, the mean time of detection
      with the combined-format HIV antigen-antibody assay was reduced by 6.15 days
      compared to that with a similar third-generation single-format HIV antibody
      assay. The quantitative sensitivity of the combination assay for the p24 antigen
      (17.5 pg/ml by use of the p24 quantitative panel VIH SFTS96') was nearly
      equivalent to that of single-format antigen tests. The combination assay
      demonstrated sensitive (100%) detection of anti-HIV immunoglobulin in specimens
      from individuals in CDC stages A, B, and C and from individuals infected with
      different HIV-1 group M subtypes, group O, or HIV-2. The apparent specificity for
      hospitalized patients (n = 1938) was 99.90%. In a random population of 7900
      volunteer blood donors, the specificity (99.87%) was comparable to that of a
      third-generation single-format HIV antibody assay (99.92%) on the same donor
      specimens. In addition, the combination assay was robust to potential interfering
      specimens. The precision of the combination was high, with intra- and interrun
      variances of <or=9.3% for each precision panel specimen or assay control and
      <or=5.3% for the negative assay control.

PMID- 14715728
TI  - Clonal and horizontal dissemination of Klebsiella pneumoniae expressing SHV-5
      extended-spectrum beta-lactamase in a Mexican pediatric hospital.
AB  - One hundred eighty-four clinical isolates of Klebsiella pneumoniae were recovered
      from August 1996 to October 1997 at the Pediatric Hospital of the Instituto
      Mexicano del Seguro Social in Mexico City, Mexico. Most of the isolates were
      collected from the neonatal intensive care unit and infant wards, which are
      located on the same floor of the hospital. Isolates were genotypically compared
      by pulsed-field gel electrophoresis with XbaI restriction of chromosomal DNA. Of
      184 clinical isolates, 91 belonged to cluster A and comprised three subtypes (A1,
      A2, and A3), while 93 isolates, comprising two minor clones, B (10 isolates) and
      C (7 isolates), and 76 unique patterns, were considered unrelated isolates (URI).
      Susceptibility patterns were indistinguishable in both groups. Fifty extended
      spectrum beta-lactamase-producing isolates, including 34 from clone A and 16 from
      URI, were examined for further studies. Molecular and genetic analysis showed
      that 47 of 50 clinical isolates expressed the SHV-5 beta-lactamase. This enzyme,
      in combination with TEM-1, was encoded in a >or=170-kb conjugative plasmid.
      Results indicate that dissemination of this resistance was due to clonal and
      horizontal spread.

PMID- 14715729
TI  - Molecular epidemiology of the iron utilization genes of enteroaggregative
      Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC) strains are etiologic agents of acute
      and persistent diarrhea. In this study, the results of phenotypic assays
      suggested that EAEC strains possess specialized iron acquisition systems. Genes
      required for the synthesis (iucA) or transport (fepC) of siderophores, and genes
      encoding siderophore (fyuA, ireA, and iroN) or heme transport (chu) receptors or
      hemoglobin proteases (pic and hbp), were sought in EAEC strains which have been
      characterized with respect to known virulence genes and phylogeny. The chuA,
      iucA, fyuA, fepC, and pic genes were detected in 33, 76.2, 85.7, 33, and 61.9% of
      these EAEC strains, respectively, and the other genes were absent. The majority
      of EAEC strains possessed genes encoding multiple iron transport systems, and
      there was no phylogenetic correlation in the distribution of the majority of
      these loci, as is typical for EAEC. The notable exceptions were chuA and fepC
      (which is associated with the prrA-modA-fepC pathogenicity island); these genes
      were restricted to the EAEC2 and DAEC2 phylogenetic groups, which could represent
      pathogenic subsets. When collections of EAEC strains isolated during case-control
      studies in Nigeria and Brazil were examined, no association of the presence of
      either chuA or iucA alone with diarrhea was seen, but both genes together were
      present in significantly more strains from cases than from controls in the
      Nigerian collection (P < 0.05). It is possible that the presence of both genes
      marks at least some virulent strains. The data also demonstrate geographical
      variation in the association of iron utilization genes with disease in EAEC.

PMID- 14715730
TI  - Multiplex real-time PCR assay for detection of influenza and human respiratory
      syncytial viruses.
AB  - A multiplex real-time PCR assay was developed with a LightCycler instrument for
      detection of influenza viruses A and B and the human respiratory syncytial virus
      (HRSV). Detection of each viral product and of an internal control was based on
      determination of specific melting temperatures by the LightCycler software. The
      lower limit of detection in the multiplex PCR assay was found to be 50 copies for
      each viral target. In an evaluation of nasopharyngeal samples collected from
      hospitalized children (ages, 0 to 3 years) with acute respiratory tract
      infections during the winter of 2001 to 2002, a viral pathogen was detected by
      the multiplex PCR test in 139 (66.8%) of 208 cases, including 45 (21.6%)
      influenza A virus infections, no (0%) influenza B virus infections, 106 (51%)
      HRSV infections, and 12 (5.8%) coinfections. The multiplex PCR test was compared
      to rapid antigen detection assays for influenza viruses A and B (Directigen;
      Becton Dickinson, Sparks, Md.) and HRSV (RSV TestPack; Abbott Laboratories,
      Abbott Park, Ill.) in 172 and 204 samples, respectively. After resolution of
      discrepant test results by use of additional PCR assays targeting other viral
      genes, the sensitivity (Se) and specificity (Sp) of the multiplex PCR assay for
      influenza A virus were 100 and 97.7% compared to 43.6 and 98.5% for the antigenic
      test. Similarly, the Se and Sp of the multiplex PCR assay for HRSV were 94.5 and
      98.9% compared to 81.6 and 94.7% for the antigenic test. In conclusion, our
      multiplex real-time PCR assay combines both rapidity and sensitivity for
      detecting the most important respiratory viral pathogens in children.

PMID- 14715731
TI  - Characterization of a novel group of mycobacteria and proposal of Mycobacterium
      sherrisii sp. nov.
AB  - We describe here the characterization of five isolates of Mycobacterium simiae
      like organisms representing a novel group based on whole-cell fatty acid analysis
      and genotypic evaluation. Two of the five isolates in this study, W55 and W58,
      were previously considered to belong to M. simiae serotype 2. Analysis of
      cellular fatty acids by gas-liquid chromatography indicated a close clustering of
      this group, which was well differentiated from the other M. simiae-like species.
      Molecular characterization was performed by nucleic acid sequencing of the small
      subunit rRNA gene and the gene encoding the 65-kDa heat shock protein and genomic
      DNA hybridization. Sequence analysis of the entire 16S rRNA gene showed a unique
      sequence most closely related to those of M. triplex and M. simiae. The hsp65
      partial gene sequence was identical for the five isolates, with 97% identity to
      the M. simiae type strain. However, qualitative whole genomic DNA hybridization
      analysis confirmed that this group is genetically distinct from M. simiae and M.
      triplex. Antimicrobial susceptibilities for this group resemble those of M.
      simiae and M. lentiflavum. We conclude that this group represents a unique
      Mycobacterium species for which we propose the name Mycobacterium sherrisii sp.
      nov.

PMID- 14715732
TI  - Practical bench comparison of BBL CHROMagar Orientation and standard two-plate
      media for urine cultures.
AB  - A total of 1023 urine samples sent for routine culture were plated onto sheep
      blood and MacConkey agars and a BBL CHROMagar Orientation (CO; Becton Dickinson,
      Cockeysville, Md.) plate, and the results were compared. Of these, 250 urine
      samples (24%) grew >10000 CFU of one or two putative pathogens/ml and 773 showed
      no growth (NG), mixed growth of <10000 CFU/ml, or three or more strains (mixed).
      The CO and conventional medium results agreed completely for 595 cultures with NG
      or <10000 CFU/ml. An additional 178 urine samples yielded clinically
      insignificant differences. Both medium sets essentially agreed on quantities and
      identification for 400 single-pathogen cultures and 9 mixed cultures. With the
      caveat that CO cannot differentiate Klebsiella, Enterobacter, and Serratia spp.,
      enteric pathogens were identified only by morphology and color on CO. Direct
      visual differentiation of group B streptococci from lactobacilli is not possible,
      but lactobacillus cells always exhibited easily recognizable morphology on Gram
      stain. Of 108 paired organism susceptibility results encompassing 2268 drug
      pathogen combinations, there were 3% errors and only 1% very major errors. Use of
      CO allowed a >50% reduction in inoculation time and a >20% reduction in work-up
      time. For our laboratory, with 50% "no growth" and ca. 25% significant results
      (50% Escherichia coli), CO allowed time and workup cost savings for a majority of
      cultures. A cost analysis (time and supplies for our laboratory) showed that if
      CO is used alone, the break-even level for CO pricing is US dollars 1.78; if CO
      and blood agar are both used, the break-even pricing for CO is US dollars 1.53.

PMID- 14715733
TI  - Detection of human anti-flavivirus antibodies with a west nile virus recombinant
      antigen microsphere immunoassay.
AB  - We report a new, suspended-microsphere diagnostic test to detect antibodies to
      West Nile (WN) virus in human serum and cerebrospinal fluid (CSF). The
      microsphere immunofluorescence assay can be performed in less than 3 h on
      specimens of <or=30 microl. A recombinant WN virus envelope (E) protein antigen
      is covalently coupled to fluorescent polystyrene microspheres. After incubation
      with diluted serum or CSF, antibodies bound to the E protein antigen are detected
      with fluorescently labeled anti-human immunoglobulin antibody and flow analysis
      in a dual-laser Luminex 100 instrument. Retrospective testing of 833 sera from
      New York patients with suspected viral encephalitis demonstrated concordance with
      results obtained with the traditional enzyme-linked immunosorbent assay for
      immunoglobulin G (IgG) antibodies to WN virus (kappa = 0.85). One hundred eighty
      eight (22.4%) of the samples, which were collected from June to November 2002,
      tested positive for antibodies to WN virus in the microsphere assay. Specimens
      depleted of IgG with anti-IgG antibody were reassayed to measure anti-E protein
      IgM antibodies and to provide an indication of current or recent WN virus
      infection. The assay also detects antibodies to E proteins from related
      flaviviruses, including St. Louis encephalitis, Japanese encephalitis, and dengue
      viruses. The new microsphere immunoassay provides a sensitive and rapid
      alternative to traditional enzyme-linked immunosorbent assays that detect
      antibodies to flavivirus E proteins. This assay can aid physicians and public
      health workers in the management of outbreaks of WN virus and related
      flaviviruses.

PMID- 14715734
TI  - Adaptive resistance to biocides in Salmonella enterica and Escherichia coli O157
      and cross-resistance to antimicrobial agents.
AB  - The mechanisms by which bacteria resist killing by antibiotics and biocides are
      still poorly defined, although repeated exposure to sublethal concentrations of
      antibacterial agents undoubtedly contributes to their development. This study
      aimed both to investigate the potential of Salmonella enterica and Escherichia
      coli O157 for adaptive resistance to commonly used biocides and to determine any
      cross-resistance to antibiotics. Strains were repeatedly passaged in media
      containing increasing concentrations of a biocide or antibiotic until adaptive
      resistance was obtained. A wide panel of antimicrobial agents was then screened
      by using the adapted strain to determine cross-resistance, if any. Adaptive
      resistance was readily achieved for both S. enterica and E. coli O157. Cross
      resistance in adaptively resistant S. enterica varied with the serotype;
      Salmonella enterica serovar Enteritidis expressed cross-resistance to
      chloramphenicol, whereas Salmonella enterica serovar Typhimurium expressed cross
      resistance to chlorhexidine. Benzalkonium chloride-resistant Salmonella enterica
      serovar Virchow showed elevated resistance to chlorhexidine; however,
      chlorhexidine-resistant Salmonella serovar Virchow did not demonstrate reciprocal
      cross-resistance to benzalkonium chloride, suggesting specific rather than
      generic resistance mechanisms. E. coli O157 strains acquired high levels of
      resistance to triclosan after only two sublethal exposures and, when adapted,
      repeatedly demonstrated decreased susceptibilities to various antimicrobial
      agents, including chloramphenicol, erythromycin, imipenem, tetracycline, and
      trimethoprim, as well as to a number of biocides. These observations raise
      concern over the indiscriminate and often inappropriate use of biocides,
      especially triclosan, in situations where they are unnecessary, whereby they may
      contribute to the development of microbial resistance mechanisms.

PMID- 14715735
TI  - Sensitivity of respiratory virus culture when screening with R-mix fresh cells.
AB  - Use of R-Mix Fresh Cells has been shown to be a rapid and sensitive method for
      the detection and identification of respiratory viruses. We prospectively
      evaluated the impact of incorporation of R-Mix shell vials on the sensitivity and
      time to detection of seven respiratory viruses recovered in a comprehensive
      culture during the course of an entire respiratory season in a high-volume
      clinical laboratory. In this study, R-Mix shell vials were used as part of the
      culture of 3803 respiratory specimens. A total of 428 respiratory viruses were
      recovered. Staining of R-Mix vials after overnight incubation allowed initial
      detection of 274 of 279 influenza viruses, 33 of 38 parainfluenza viruses, 35 of
      51 adenoviruses, and 52 of 60 respiratory syncytial viruses (RSVs). The time to
      reporting of all positive cultures after in-lab specimen receipt was 2.9 days on
      average and those initially detected in R-Mix cells were reported in 2.3 days on
      average. A combination of direct fluorescent-antibody (DFA) staining and virus
      culture was performed on a subset of 711 respiratory specimens. Of 152 viruses
      identified, 57 were observed only with DFA testing (55 RSV and 2 influenza A
      viruses) and 31 were recovered only in cell culture. After overnight incubation,
      R-Mix cells detected 87.1% of respiratory viruses not observed by DFA testing and
      96.9% of viruses positive by both methods. The sensitivities of DFA testing and R
      Mix cells for identification of influenza viruses were 70.5% and 96.7%,
      respectively. The R-Mix method detected influenza virus in 18 samples that were
      negative by DFA testing.

PMID- 14715736
TI  - Dynamics of Streptococcus agalactiae colonization in women during and after
      pregnancy and in their infants.
AB  - The population dynamics of Streptococcus agalactiae (group B streptococci [GBS])
      colonization of the vagina and anorectal area was investigated in a cohort of 77
      Danish women during and after their pregnancy by a new sensitive method. The mean
      carriage rate among individual observations was 36%, and the cumulative carriage
      rate over the entire observation period was 54%. Examination of more than 1500
      GBS isolates by pulsed-field gel electrophoresis demonstrated that the GBS
      population was remarkably homogeneous and stable in each carrier. Virtually all
      carriers were colonized by a single GBS clone on all occasions spanning up to 2
      years. Repeated detection of the same clone even in women who were recorded as
      intermittent carriers suggests that the actual carrier rate exceeds 50% but that
      fluctuations in the GBS proportions of the flora occasionally preclude their
      detection. Newborns and young infants usually carried the same GBS clone as their
      mothers. However, only twice were identical clones of GBS detected in different
      women in contrast to the observed clonal relationships of clinical isolates.
      These observations strongly suggest differences in the properties and
      epidemiology of virulent GBS clones compared to clones commonly carried by
      healthy individuals.

PMID- 14715737
TI  - Rickettsia species infecting Amblyomma cooperi ticks from an area in the state of
      Sao Paulo, Brazil, where Brazilian spotted fever is endemic.
AB  - Owing to the potential role of the tick Amblyomma cooperi in the enzootic cycle
      of Rickettsia rickettsii, the etiologic agent of Brazilian spotted fever (BSF),
      this study evaluated infection by Rickettsia species in A. cooperi ticks
      collected from an area in Brazil where BSF is endemic. Among a total of 40 A.
      cooperi adult ticks collected in an area of BSF endemicity in the state of Sao
      Paulo, PCR analysis detected DNA of Rickettsia bellii in 16 ticks (40%), and 3
      other ticks (7.5%) were positive for a previously unidentified spotted-fever
      group (SFG) rickettsia. Cultivation in Vero cell cultures by the shell vial
      technique with individual A. cooperi ticks resulted in two isolates of R. bellii
      and one isolate genotypically characterized as an SFG rickettsia. The two R.
      bellii isolates were established in Vero cell cultures in the laboratory and were
      confirmed to be R. bellii by molecular analysis of the gltA and 17-kDa protein
      encoding genes and by electron microscopic analysis. The SFG rickettsial isolate
      could not be stably passaged in cell culture in the laboratory, but molecular
      analysis of early passages suggested that it was closely related to Rickettsia
      parkeri, Rickettsia africae, and Rickettsia sibirica. These results do not
      support the role of A. cooperi in the ecology of R. rickettsii in the area
      studied, but they add two more species of rickettsiae to the poorly developed
      list of species occurring in ticks in South America.

PMID- 14715738
TI  - Infection with a proposed new subspecies of Babesia canis, Babesia canis subsp.
      presentii, in domestic cats.
AB  - Parasitemia with a large Babesia species was identified in two domestic cats from
      Israel. One cat, also coinfected with feline immunodeficiency virus and
      "Candidatus Mycoplasma haemominutum," had profound icterus and anemia which
      resolved after therapy, whereas a second cat was an asymptomatic carrier.
      Amplification and sequencing of the 18S rRNA gene, followed by phylogenetic
      analyses, indicated that infection was caused by Babesia canis. However, the
      sequences of the internal transcribed and 5.8S rRNA regions of the ribosomal
      operon used for subspeciation of B. canis were markedly different from the
      recognized subspecies of B. canis, which include B. canis vogeli, B. canis canis,
      and B. canis rossi. Based on phylogenetic comparisons of the 18S rRNA gene, 5.8S,
      and internal transcribed spacer sequences of the isolates from the cats and on
      the smaller sizes of the merozoite and trophozoite stages of this parasite, which
      distinguish it from the subspecies of B. canis present in dogs, we propose to
      identify the novel feline genotype of B. canis described in the present study as
      a new subspecies, B. canis subsp. presentii.

PMID- 14715739
TI  - Expression and immunogenicity of proteins encoded by sequences specific to
      Mycobacterium avium subsp. paratuberculosis.
AB  - The development of immunoassays specific for the diagnosis of Johne's disease in
      cattle requires antigens specific to Mycobacterium avium subsp. paratuberculosis.
      However, because of genetic similarity to other mycobacteria comprising the M.
      avium complex, no such antigens have been found. Through a comparative genomics
      approach, 21 potential coding sequences of M. avium subsp. paratuberculosis that
      are not represented in any other mycobacterial species tested (n = 9) were
      previously identified (J. P. Bannantine, E. Baechler, Q. Zhang, L. Li, and V.
      Kapur, J. Clin. Microbiol. 40:1303-1310, 2002). Here we describe the cloning,
      heterologous expression, and antigenic analysis of these M. avium subsp.
      paratuberculosis-specific sequences in Escherichia coli. Nucleotide sequences
      representing each unique predicted coding region were amplified and cloned into
      two different E. coli expression vectors encoding polyhistidine or maltose
      binding protein (MBP) affinity purification tags. All 21 of the MBP fusion
      proteins were successfully purified under denaturing conditions and were
      evaluated in immunoblotting studies with sera from rabbits and mice immunized
      with M. avium subsp. paratuberculosis. These studies showed that 5 of the 21 gene
      products are produced by M. avium subsp. paratuberculosis and are antigenic.
      Immunoblot analysis with a panel of sera from 9 healthy cattle and 10 cattle with
      clinical disease shows that the same five M. avium subsp. paratuberculosis
      proteins are also detected within the context of infection. Collectively, these
      studies have used a genomic approach to identify novel M. avium subsp.
      paratuberculosis antigens that are not present in any other mycobacteria. These
      findings may have a major impact on improved diagnostics for Johne's disease.

PMID- 14715740
TI  - Direct comparison of the BACTEC 9240 and BacT/ALERT 3D automated blood culture
      systems for candida growth detection.
AB  - A direct comparison of two automated blood culture systems was conducted to
      compare their ability to detect Candida growth. The systems evaluated were the
      BACTEC 9240 (Bactec) and BacT/ALERT 3D (BacT). The aerobic, anaerobic, and
      mycology media for each system were evaluated: Bactec Plus Aerobic/F, Plus
      Anaerobic/F, and Myco/F Lytic bottles, respectively, and BacT FA, SN, and MB
      bottles, respectively. Each blood culture bottle was inoculated with fresh blood
      from healthy donors. Fifty isolates of Candida spp. were used. The six different
      blood culture bottles were each inoculated with 1000 yeasts per bottle and then
      incubated in the corresponding automated system. The BacT detected growth of 90%
      (135 of 150) of Candida pathogens, while Bactec detected 66% (100 of 150). Growth
      was detected in all BacT and Bactec mycology bottles, all BacT aerobic bottles,
      and by terminal subculture of all bottles. Sixty-five of 300 (22%) bottles had no
      growth detected; 50 from the Bactec (5 aerobic and 45 anaerobic) and 15 from the
      BacT (all anaerobic). Terminal subculture of "negative" bottles demonstrated
      viable yeast growth from all 65 bottles, representing 65 false-negatives. The
      mean time to growth detection in the BacT system was 25.62 h while the Bactec was
      27.30 h (P < 0.01). Both automated blood culture systems detected all episodes of
      simulated candidemia when specialized mycology media were used. However, when
      only standard aerobic and anaerobic media were used, the BacT performed better
      than the Bactec in overall growth detection, time to growth detection, and number
      of false-negatives.

PMID- 14715741
TI  - Molecular analysis of Mycobacterium kansasii isolates from the United States.
AB  - We studied the population genetics of Mycobacterium kansasii isolates from the
      United States by PCR restriction enzyme analysis (PRA) of the 441-bp Telenti
      fragment of the hsp-65 gene and pulsed-field gel electrophoresis (PFGE) of
      genomic DNA with the restriction endonucleases AseI, DraI, and XbaI, and we
      compared the patterns to those previously reported from France and Japan. By PRA,
      78 of 81 clinical isolates (96%) from the United States belonged to subspecies I.
      With PFGE, 28 AseI patterns, 32 DraI patterns, and 35 XbaI patterns were
      produced. PFGE showed marked clonality of the U.S. isolates, with differences
      between genotypes involving only one or two bands. Isolates within Texas showed
      lower pattern diversity than those from different states. With DraI, 31 of 71
      isolates (44%) had the same common PFGE pattern, which matched the predominant
      pattern in France (pattern Ia), determined by Picardeau et al. (M. Picardeau, G.
      Prod'hom, L. Raskine, M. P. LePennec, and V. Vincent, J. Clin. Microbiol. 35:25
      32, 1997), and in Japan (type M), determined by Iinuma et al. (Y. Iinuma, S.
      Ichiyama, Y. Hasegawa, K. Shimokata, S. Kawahara, and T. Matsushima, J. Clin.
      Microbiol. 35:596-599, 1997). With AseI, 42% of isolates produced a common
      pattern indistinguishable from the common pattern seen in French isolates (Ia)
      and with only one band difference from the common pattern (type M) in Japan. This
      study demonstrates that subspecies I is the predominant subspecies of M. kansasii
      among clinical isolates in the United States, as it is in Europe and Japan, and
      that genotype I is highly clonal worldwide, with the same major genotype
      responsible for human infection. The fact that a single clone of M. kansasii is
      responsible for most cases of human disease suggests that specific virulence
      factors may be associated with this specific genotype.

PMID- 14715742
TI  - Human metapneumovirus infection in Japanese children.
AB  - Human metapneumovirus (hMPV) has been recently discovered as an etiological agent
      of acute respiratory infections. Our purpose was to asses the virological and
      clinical features of children with respiratory infections caused by hMPV. We
      examined 658 nasopharyngeal swab samples obtained from 637 children with
      respiratory infections for hMPV by using reverse transcription-PCR (RT-PCR). A
      total of 268 samples from 637 children were inoculated onto tertiary monkey
      kidney cells. A total of 36 serum samples (26 in the acute phase and 10 in the
      convalescent phase) from the 26 hMPV-positive children were tested for
      immunoglobulin G (IgG) and IgM antibodies to hMPV by using an indirect
      immunofluorescence assay. We detected hMPV in 57 (8.9%) of the 637 samples by
      using RT-PCR and isolated 7 (2.6%) hMPV strains of the 268 samples in cell
      cultures. A total of 12 (46.2%) of 26 hMPV-positive children were suspected to
      have primary infection with hMPV as determined by an indirect immunofluorescence
      assay. The infected children were diagnosed as having wheezy bronchitis (36.8%),
      upper respiratory tract infection (26.3%), bronchitis (22.8%), and pneumonia
      (14.0%). We showed that two hMPV groups were circulating in different regions
      during the same period and that reinfection with hMPV frequently occurs in
      childhood. The RT-PCR test is the most sensitive test for detection of hMPV, and
      a serological test may be useful to differentiate between primary infection and
      reinfection with hMPV.

PMID- 14715743
TI  - Typical enteroaggregative Escherichia coli is the most prevalent pathotype among
      E. coli strains causing diarrhea in Mongolian children.
AB  - Diarrhea remains one of the main sources of morbidity and mortality in the world,
      and a large proportion is caused by diarrheagenic Escherichia coli. In Mongolia,
      the epidemiology of diarrheagenic E. coli has not been well studied. A total of
      238 E. coli strains from children with sporadic diarrhea and 278 E. coli strains
      from healthy children were examined by PCR for 10 virulence genes:
      enteropathogenic E. coli (EPEC) eae, tir, and bfpA; enterotoxigenic E. coli
      (ETEC) lt and st; enteroinvasive E. coli (EIEC) ipaH; enterohemorragic E. coli
      stx1 and stx2; and enteroaggregative E. coli (EAEC) aggR and astA. EAEC strains
      without AggR were identified by the HEp-2 cell adherence test. The detection of
      EAEC, ETEC, EPEC, and EIEC was significantly associated with diarrhea. The
      incidence of EAEC (15.1%), defined by either a molecular or a phenotypic assay,
      was higher in the diarrheal group than any other category (0 to 6.0%). The
      incidence of AggR-positive EAEC in the diarrheal group was significantly higher
      than in the control group (8.0 versus 1.4%; P = 0.0004), while that of AggR
      negative EAEC was not (7.1 versus 4.3%). Nineteen AggR-positive EAEC strains
      harbored other EAEC virulence genes-aggA, 2 (5.5%); aafA, 4 (11.1%); agg-3a, 5
      (13.8%); aap, 8 (22.2%); aatA, 11 (30.5%); capU, 9 (25.0%); pet, 6 (16.6%); and
      set, 3 (8.3%)-and showed 15 genotypes. EAEC may be an important pathogen of
      sporadic diarrhea in Mongolian children. Genetic analysis showed the
      heterogeneity of EAEC but illustrated the importance of the AggR regulon
      (denoting typical EAEC) as a marker for virulent EAEC strains.

PMID- 14715744
TI  - Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification
      method, loop-mediated isothermal amplification.
AB  - A novel nucleic acid amplification method, termed loop-mediated isothermal
      amplification (LAMP), which amplifies DNA with high specificity, efficiency, and
      rapidity under isothermal conditions, may be a valuable tool for the rapid
      detection of infectious agents. LAMP was developed for human herpesvirus 6 (HHV
      6), and its reliability was evaluated in this study. Although LAMP products were
      detected in HHV-6 B and HHV-6 A DNA, they were not detected in HHV-7 and human
      cytomegalovirus DNA. The sensitivity of the original HHV-6 LAMP protocol was 50
      copies/tube. In order to increase the method's sensitivity, HHV-6 LAMP was
      modified by increasing the primer concentration. As a result of the modification,
      sensitivity increased to 25 copies/tube. After these initial validation studies,
      13 patients with fever were tested for HHV-6 by viral isolation, serological
      analysis, and HHV-6 LAMP. In three of the eight patients with primary HHV-6
      infection, HHV-6 DNA was detected in whole blood by the original HHV-6 LAMP
      protocol in not only the acute phase but also the convalescent phase. HHV-6 DNA
      was detected by modified HHV-6 LAMP in all eight plasma samples collected in the
      acute phase; however, no HHV-6 DNA was detected in plasma samples collected in
      the convalescent phase. Although HHV-6 DNA was detected in both the acute and
      convalescent phases of whole-blood samples in patients with past HHV-6 infection,
      it was not detected in plasma samples that did not contain latent viral DNA.
      Thus, detection of HHV-6 DNA in plasma by using this modified HHV-6 LAMP protocol
      is appropriate for diagnosis of active HHV-6 infection.

PMID- 14715745
TI  - Comparison of DNA dot blot hybridization and lancefield capillary precipitin
      methods for group B streptococcal capsular typing.
AB  - Group B streptococci (GBS) (Streptococcus agalactiae) are a major cause of sepsis
      and meningitis in neonates and infants and of invasive disease in pregnant women,
      nonpregnant, presumably immunocompromised adults, and the elderly. Nine GBS
      serotypes based on capsular polysaccharide antigens have been described. The
      serotype distributions among invasive and colonizing isolates differ between
      pediatric and adult populations and have changed over time. Thus, periodic
      monitoring of GBS serotype distributions is necessary to ensure the proper
      formulation and application of an appropriate GBS vaccine for human use and to
      detect the emergence of novel serotypes. Since the mid-1990s, the proportion of
      GBS isolates that are nontypeable by standard serologic methods has increased,
      creating a need for more sensitive typing methods. We describe a typing method
      that uses DNA dot blot hybridization with probes generated by PCR from the GBS
      capsular genes for serotypes Ia, Ib, and II to VIII. PCR primers were designed to
      amplify type-specific GBS capsular gene sequences. Gene probes were constructed
      from the PCR products and used to classify isolates based on hybridization
      profiles. A total of 306 previously serotyped invasive and colonizing isolates
      were used to compare our dot blot capsular typing (DBCT) identification method
      with Lancefield serotyping (LS). A dot blot capsular type was assigned to 99%
      (303 of 306) of the isolates, whereas 273 of 306 isolates (89%) were assigned a
      Lancefield serotype. The overall agreement between the methods was 95% (256 of
      270 isolates typeable by both methods). We conclude that the DBCT method is a
      specific and useful alternative to the commonly used LS method.

PMID- 14715746
TI  - Prevalence and genetic diversity of human astroviruses in Mexican children with
      symptomatic and asymptomatic infections.
AB  - The prevalence and type diversity of human astroviruses (HAstV) in children with
      symptomatic and asymptomatic infections were determined in five localities of
      Mexico. HAstV were detected in 4.6 (24 of 522) and 2.6% (11 of 428) of children
      with and without diarrhea, respectively. Genotyping of the detected strains
      showed that at least seven (types 1 to 4 and 6 to 8) of the eight known HAstV
      types circulated in Mexico between October 1994 and March 1995. HAstV types 1 and
      3 were the most prevalent in children with diarrhea, although they were not found
      in all localities studied. HAstV type 8 was found in Mexico City, Monterrey, and
      Merida; in the last it was as prevalent (40%) as type 1 viruses, indicating that
      this astrovirus type is more common than previously recognized. A correlation
      between the HAstV infecting type and the presence or absence of diarrheic
      symptoms was not observed. Enteric adenoviruses were also studied, and they were
      found to be present in 2.3 (12 of 522) and 1.4% (6 of 428) of symptomatic and
      asymptomatic children, respectively.

PMID- 14715747
TI  - Hepatitis C genotyping by denaturing high-performance liquid chromatography.
AB  - Determination of the hepatitis C virus (HCV) genotype for infected patients
      increasingly has become accepted as the standard of care. Genotype assignment
      helps in assessing disease prognosis and assists in establishing the appropriate
      duration of treatment. The great genetic diversity of HCV, with 11 major
      genotypes and >70 subtypes, contributes to the technical difficulty of genotype
      testing. While the "gold standard" for testing is nucleic acid sequencing, a
      variety of hybridization assays, including the line probe assay, have been
      developed to provide more rapid and accessible forms of testing. The aim of this
      study was to determine whether denaturing high-performance liquid chromatography
      (dHPLC) could be used as a clinical method for distinguishing HCV genotypes 1, 2,
      3, and 4. A portion of the 5' untranslated region of the HCV genome was amplified
      by heminested multiplex reverse transcription PCR. The two amplicons then were
      analyzed by dHPLC analysis and compared to the genotypes determined by sequence
      analysis. After 115 specimens were analyzed as standards, 200 masked specimens
      (specimens whose identity was not known before testing) were analyzed to
      determine the concordance of the assay. The assay had a concordance of 96% at the
      genotype level and a concordance of 87% at the subtype level. However, the dHPLC
      method was not as accurate as other reported methods of HCV genotyping. This is
      the first time that HCV genotyping has been performed by dHPLC.

PMID- 14715748
TI  - Increased sensitivity of mannanemia detection tests by joint detection of alpha-
      and beta-linked oligomannosides during experimental and human systemic
      candidiasis.
AB  - An enzyme immunoassay (EIA)-the commercially available Platelia Candida antigen
      test-developed for the diagnosis of systemic candidiasis is based on the
      detection of alpha-linked oligomannose residues (alpha-Man) released from Candida
      cells into the serum. This test has good specificity but has to be repeated
      frequently because of the rapid clearance of detectable mannanemia. We have
      developed a second EIA based on detection of beta-linked oligomannoses (beta
      Man), since beta-Man are linked to different Candida molecules and interact
      differently with the host immune system and endogenous lectins and should
      therefore present different kinetics of serum clearance. In a guinea pig model of
      Candida albicans systemic infection, the relative amounts of detectable alpha-
      and beta-Man differed considerably according to the virulence of the strain, the
      infecting dose, and the time after challenge that serum samples were drawn.
      Detection of alpha-Man was more sensitive per serum sample than that of beta-Man,
      and the sensitivity for the combination reached 90%. The same tests were applied
      to 90 sera from 26 patients selected retrospectively for having been infected
      with the most-pathogenic Candida species: C. albicans (19), C. tropicalis (4),
      and C. glabrata (3). A total of 22 patients had positive antigenemia, 4 had alpha
      mannanemia, 4 had beta-mannanemia, and 14 showed the presence of both. For the
      patients showing the presence of both forms of mannanemia, the use of both tests
      enhanced the duration of the detection of mannanemia. Mannanemia was correlated
      with early clinical symptoms and isolation of Candida in culture, which occurred
      in 55% of the patients at an average of 4.7 days after the first positive
      mannanemia test result. A combination of the two tests had a cumulated
      specificity of 95%, and positive and negative predictive values were 79 and 97%,
      respectively. These findings provide evidence for different kinetics of beta- and
      alpha-Man circulation during experimental and human candidiasis and suggest the
      joint detection of both types of epitopes as a rational approach contributing to
      increases in the sensitivity and earliness of diagnosis.

PMID- 14715749
TI  - Decision support tools for clinical diagnosis of disease in cows with suspected
      bovine spongiform encephalopathy.
AB  - Reporting of clinically suspected cattle is currently the most common method for
      detecting cases of bovine spongiform encephalopathy (BSE). Improvement of
      clinical diagnosis and decision-making remains crucial. A comparison of clinical
      patterns, consisting of 25 signs, was made between all 30 BSE cases, confirmed in
      Belgium before October 2002, and 272 suspected cases that were subsequently
      determined to be histologically, immunohistochemically, and scrapie-associated
      fiber negative. Seasonality in reporting suspected cases was observed, with more
      cases being reported during wintertime when animals were kept indoors. The median
      duration of illness was 30 days. The 10 most relevant signs of BSE were kicking
      in the milking parlor, hypersensitivity to touch and/or sound, head shyness,
      panic-stricken response, reluctance to enter in the milking parlor, abnormal ear
      movement or carriage, increased alertness behavior, reduced milk yield, teeth
      grinding, and temperament change. Ataxia did not appear to be a specific sign of
      BSE. A classification and regression tree was constructed by using the following
      four features: age of the animal, year of birth, number of relevant BSE signs
      noted, and number of clinical signs, typical for listeriosis, noted. The model
      had a sensitivity of 100% and a specificity of 85%. This approach allows the use
      of an interactive decision-support tool, based entirely on odds ratios, a
      statistic independent of disease prevalence.

PMID- 14715750
TI  - Detection of the Bacillus anthracis gyrA gene by using a minor groove binder
      probe.
AB  - Identification of chromosomal markers for rapid detection of Bacillus anthracis
      is difficult because significant chromosomal homology exists among B. anthracis,
      Bacillus cereus, and Bacillus thuringiensis. We evaluated the bacterial gyrA gene
      as a potential chromosomal marker for B. anthracis. A real-time PCR assay was
      developed for the detection of B. anthracis. After analysis of the unique
      nucleotide sequence of the B. anthracis gyrA gene, a fluorescent 3' minor groove
      binding probe was tested with 171 organisms from 29 genera of bacteria, including
      102 Bacillus strains. The assay was found to be specific for all 43 strains of B.
      anthracis tested. In addition, a test panel of 105 samples was analyzed to
      evaluate the potential diagnostic capability of the assay. The assay showed 100%
      specificity, demonstrating the usefulness of the gyrA gene as a specific
      chromosomal marker for B. anthracis.

PMID- 14715752
TI  - Development of a dipstick assay for detection of Leishmania-specific canine
      antibodies.
AB  - A dipstick assay, based on Leishmania infantum antigen, for the rapid detection
      of Leishmania-specific antibodies in canine serum samples was developed and
      evaluated. After determination of optimal dipstick test conditions, test
      performance was compared with two existing serological tests, i.e., the direct
      agglutination test (DAT) and the fast agglutination screening test (FAST). In the
      present study the dipstick test had a sensitivity of 99.2% and a specificity of
      87.9%. The DAT had a sensitivity of 97.7% and a specificity of 95.2%, whereas the
      FAST had also a sensitivity of 97.7% and a specificity of 93.0%. High degrees of
      agreement were observed between the dipstick test and DAT (93.7%; kappa value,
      0.86), between the dipstick test and FAST (91.8%; kappa value, 0.82), and between
      the DAT and FAST (95.2%; kappa value, 0.90). The high sensitivity and ease of
      performance make the dipstick test very suitable for surveillance surveys.

PMID- 14715751
TI  - Characterization of group C and G streptococcal strains that cause streptococcal
      toxic shock syndrome.
AB  - Twelve strains (the largest number ever reported) of group C and G(1)
      streptococci (GCS and GGS, respectively) that caused streptococcal toxic shock
      syndrome (STSS) were collected and characterized. Eleven strains were identified
      as Streptococcus dysgalactiae subsp. equisimilis, and one strain was identified
      as Streptococcus equi subsp. zooepidemicus. We found that it was the first
      reported case of STSS caused by S. equi subsp. zooepidemicus. Cluster analysis
      according to the 16S rRNA gene (rDNA) sequences revealed that the S. dysgalactiae
      strains belonged to clusters I and II, both of which were closely related. The
      emm types and the restriction patterns of chromosomal DNA measured by pulsed
      field gel electrophoresis were highly variable in these strains except BL2719 and
      N1434. The 16S rDNA sequences and other characteristics of these two strains were
      indistinguishable, suggesting the clonal dissemination of this particular S.
      dysgalactiae strain in Japan. As the involvement of superantigens in the
      pathogenesis of group A streptococcus-related STSS has been suggested, we tried
      to detect known streptococcal superantigens in GCS and GGS strains. However, only
      the spegg gene was detected in seven S. dysgalactiae strains, with none of the
      other superantigen genes being detected in any of the strains. However, the sagA
      gene was detected in all of the strains except Tokyo1291. In the present study no
      apparent factor(s) responsible for the pathogenesis of STSS was identified,
      although close genetic relationships of GCS and GGS strains involved in this
      disease were suggested.

PMID- 14715753
TI  - Demonstration of Streptococcus mutans with a cell wall polysaccharide specific to
      a new serotype, k, in the human oral cavity.
AB  - Streptococcus mutans organisms are occasionally isolated from the blood of
      patients with infective endocarditis, though the mechanisms of invasion and
      survival remain to be elucidated. Two of four blood isolates from patients with
      bacteremia or infective endocarditis (strains TW295 and TW871) were serologically
      untypeable by immunodiffusion testing, which was due to a lack of the glucose
      side chain of the serotype-specific polysaccharide antigen of S. mutans.
      Immunodiffusion analyses using antisera against these strains demonstrated that 2
      of 100 isolates from 100 subjects showed a positive reaction, while further
      analysis of 2500 isolates from 50 subjects revealed that all 50 isolates from a
      single subject were not reactive with anti-c, -e, and -f antisera, though they
      were reactive with anti-TW295 and -TW871 antisera. The oral isolates showed
      biological properties similar to those of the reference S. mutans strain MT8148,
      including high levels of sucrose-dependent adhesion and cellular hydrophobicity,
      along with expression of glucosyltransferases and a protein antigen, PA. We
      designated these organisms serotype k. A glucose side chain-defective mutant
      strain was then constructed by insertional inactivation of the gluA gene of
      strain MT8148, which showed biological properties similar to those of serotype k
      of S. mutans. Serotype k oral isolates were less susceptible to phagocytosis, as
      were the gluA-inactivated mutant of strain MT8148 and blood isolates. These
      results indicate that S. mutans serotype k strains are present in the oral cavity
      in humans and may be able to survive longer in blood owing to their low
      susceptibility to phagocytosis.

PMID- 14715754
TI  - Diagnostic assessment of Mycoplasma genitalium in culture-positive women.
AB  - Detection of Mycoplasma genitalium-mediated, chlamydia-negative nongonococcal
      urethritis and other M. genitalium-linked infectious etiologies has been very
      challenging. Although M. genitalium is considered a leading cause of
      genitourinary symptoms in men and women, extreme difficulties in its cultivation
      due to its highly fastidious nature and the lack of routine and effective
      diagnostic tests have slowed the generation of clinical data which directly
      implicate the presence of M. genitalium in disease pathogenesis. In this study,
      we compared enzyme-linked immunosorbent assays (ELISAs) and immunoblot and PCR
      assays in M. genitalium culture-positive women over 1 to 3 years of clinical
      visits to determine the usefulness of independent diagnostic strategies.
      Furthermore, the value of combinatorial diagnostic assessments is described,
      which provides insights into the dynamics of M. genitalium-host interactions.
      Overall, we show that neither ELISA nor PCR, alone or in combination, provides
      the sensitivity required to confidently predict the existence of viable M.
      genitalium organisms in cervical and vaginal samples. Additionally, culture
      positive women exhibited a range of antibody responsiveness to M. genitalium
      based upon ELISA and immunoblot assessments, indicating immune diversity among
      this high-risk population.

PMID- 14715756
TI  - Typing of clinical and environmental Aeromonas sp. strains by random amplified
      polymorphic DNA PCR, repetitive extragenic palindromic PCR, and enterobacterial
      repetitive intergenic consensus sequence PCR.
AB  - A collection of 120 strains isolated from stool specimens collected from humans
      suffering from gastroenteritis and from environmental samples were analyzed by
      random amplified polymorphic DNA PCR (RAPD), repetitive extragenic palindromic
      PCR (REP-PCR), and enterobacterial repetitive intergenic consensus sequence PCR
      (ERIC-PCR). Species of Aeromonoas hydrophila, A. bestiarum, A. salmonicida, A.
      caviae, A. media, and A. veronii revealed clonal structure. There was no dominant
      clone causing gastroenteritis in humans. Moreover, there was no genetic
      similarity between clinical and environmental strains of Aeromonas sp. isolated
      from different geographical areas as well as from the same geographical area.
      Some clones colonized specific ecosystems, e.g., drinking water distribution
      systems. RAPD and ERIC-PCR methods had the same discriminatory power and proved
      to be useful for epidemiological investigation and population genetic analysis of
      Aeromonas spp., whereas REP-PCR was less effective for differentiating the
      isolates of Aeromonas spp.

PMID- 14715755
TI  - IS6110 mediates increased transcription of the phoP virulence gene in a multidrug
      resistant clinical isolate responsible for tuberculosis outbreaks.
AB  - Drug resistance in Mycobacterium tuberculosis complex strains is solely due to
      chromosomal mutations that could affect bacterial virulence. Molecular
      epidemiology studies have shown that resistant strains are less likely to be
      clustered than susceptible strains. However, a few multidrug-resistant (MDR) M.
      tuberculosis complex strains have been described as causing outbreaks, suggesting
      that they have restored virulence or increased transmission. One of the biggest
      MDR tuberculosis outbreaks documented to date was caused by the B strain of M.
      bovis. Restriction fragment length polymorphism fingerprinting revealed that the
      B strain contains two copies of IS6110. Here, we mapped and sequenced the regions
      flanking the two copies of IS6110 in the B strain. Ligation-mediated PCR showed
      that one of these IS6110 copies is located within the promoter region of phoP, a
      transcriptional regulator that is essential for M. tuberculosis virulence. We
      used PCR to screen 219 MDR M. tuberculosis complex strains (90.4% of all MDR
      isolates) isolated in Spain between 1998 and 2002 and found that the B strain was
      the only strain that contained a copy of IS6110 in the phoP promoter. To
      determine whether IS6110 affects phoP promoter activity in the B strain, we
      individually cloned the phoP gene and its promoter region (including IS6110 from
      the B strain and the equivalent region from M. tuberculosis without IS6110 as a
      control) into a mycobacterial replicative plasmid and transformed M. smegmatis
      with the resulting plasmid. Primer extension analysis showed that phoP
      transcription was strongly upregulated when the promoter region contained IS6110,
      as in the case of the B strain.

PMID- 14715757
TI  - Fluorescent amplified fragment length polymorphism genotyping of Campylobacter
      jejuni and Campylobacter coli strains and its relationship with host specificity,
      serotyping, and phage typing.
AB  - Fluorescent amplified fragment length polymorphism (FAFLP) analysis was applied
      to 276 Campylobacter jejuni strains and 87 Campylobacter coli strains isolated
      from humans, pigs, cattle, poultry, and retail meats to investigate whether
      certain FAFLP genotypes of C. jejuni and C. coli are associated with a particular
      host and to determine the degree of association between FAFLP-defined genotypes
      and heat-stable serotypes and/or phage types. Within C. coli, the poultry strains
      clustered separately from those of porcine origin. In contrast, no evidence of
      host specificity was detected among C. jejuni strains. While C. coli strains show
      host specificity by FAFLP genotyping, C. jejuni strains that are genotypically
      similar appear to colonize a range of hosts, rather than being host adapted. Some
      serotypes and/or phage types (C. jejuni serotype HS18, phage type PT6, and
      serophage type HS19/PT2 and C. coli HS66, PT2, and HS56/PT2) were the most
      homogeneous by FAFLP genotyping, while others were more heterogeneous (C. jejuni
      HS5 and PT39, and C. coli HS24 and PT44) and therefore poor indicators of genetic
      relatedness between strains. The lack of host specificity in C. jejuni suggests
      that tracing the source of infection during epidemiological investigations will
      continue to be difficult. The lack of congruence between some serotypes and/or
      phage types and FAFLP genotype underlines the need for phenotypic testing to be
      supplemented by genotyping. This study also demonstrates how, in general, FAFLP
      generates "anonymous" genetic markers for strain characterization and
      epidemiological investigation of Campylobacter in the food chain.

PMID- 14715758
TI  - Nonvalue of culturing cerebrospinal fluid for fungi.
AB  - No studies have evaluated the efficacy of culturing cerebrospinal fluid (CSF) for
      fungi. Because of the facts that the most common fungi responsible for meningitis
      grow well in media utilized for routine bacterial cultures and that cryptococcal
      antigen tests are commonly ordered, the efficacy of routinely performing fungal
      cultures specifically to recover fungi has been questioned. We examined data from
      1225 samples of CSF which were cultured for both bacteria and fungi. Twelve
      specimens yielded fungi, 10 from fungal cultures and 8 from bacterial cultures.
      Cryptococcus neoformans was found in 10 specimens, Candida albicans was found in
      1, and a Cladosporium sp. was found in 1. Eight of 12 positive specimens had
      concordant culture results. The discordant cases were one specimen that was
      bacterial culture positive but fungal culture negative and three specimens that
      were fungal culture positive but bacterial culture negative. Of the latter
      discrepant cultures, one had fungal contamination only and the other two were
      positive for cryptococcal antigen. Therefore, omitting the fungal cultures on
      these specimens would not adversely impact patients. When both cryptococcal
      antigen tests and bacterial cultures are ordered routinely, eliminating fungal
      cultures on CSF would have had no impact on the patients in this study. All the
      clinically significant fungi were detected by the cryptococcal antigen test
      and/or bacterial culture. With a few exceptions, the combined use of cryptococcal
      antigen test and bacterial cultures of CSF could replace routine fungal cultures
      of CSF. Exceptions include settings where fungal pathogens other than
      Cryptococcus and Candida remain important causes of meningitis.

PMID- 14715759
TI  - Validation of roche COBAS Amplicor assay for detection of Chlamydia trachomatis
      in rectal and pharyngeal specimens by an omp1 PCR assay.
AB  - Screening guidelines for men who have sex with men (MSM) recommend testing of
      extragenital sites (pharyngeal and rectal) for gonorrhoea and chlamydia. Testing
      of specimens from these sites is not validated by most commercial nucleic
      amplification tests, such as the COBAS Amplicor assay. To investigate the utility
      of the COBAS Amplicor assay for detection of Chlamydia trachomatis in
      extragenital specimens, this study developed and evaluated confirmatory tests
      using the omp1 gene as an alternative target for amplification by PCR. Of anal
      and throat swabs collected from men in male-only saunas, 52 swabs that tested C.
      trachomatis positive by COBAS Amplicor and 30 swabs that tested as negative were
      included for confirmatory omp1 PCR testing. A total of 49 (94%) COBAS Amplicor
      positive samples were confirmed by the omp1 PCR. A substantial proportion of
      specimens were confirmed by using a nested omp1 PCR (27%). Not confirmed by any
      omp1 PCR were three anal swabs (6%). It is most probable that these samples
      contained lower bacterial levels that were near or below the detection level of
      the omp1 PCR assays. The findings of this study support the confident reporting
      of C. trachomatis detected by COBAS Amplicor in extragenital specimens and
      support the utility of this assay as a screening test for MSM.

PMID- 14715760
TI  - Surveillance network for herpes simplex virus resistance to antiviral drugs: 3
      year follow-up.
AB  - Herpes simplex virus (HSV) infections are very common in the general population
      and among immunocompromised patients. Acyclovir (ACV) is an effective treatment
      which is widely used. We deemed it essential to conduct a wide and coordinated
      survey of the emergence of ACV-resistant HSV strains. We have formed a network of
      15 virology laboratories which have isolated and identified, between May 1999 and
      April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The
      sensitivity of each isolate to ACV was evaluated by a colorimetric test (C.
      Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217,
      2002). During this study, 3900 isolated strains among 3357 patients were
      collected; 55% of the patients were immunocompetent. Only six immunocompetent
      patients excreted ACV-resistant HSV strains (0.32%), including one female patient
      not treated with ACV who was infected primary by an ACV-resistant strain. Among
      the 54 immunocompromised patients from whom ACV-resistant HSV strains were
      isolated (3.5%), the bone marrow transplantation patients showed the highest
      prevalence of resistance (10.9%), whereas among patients infected by human
      immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the
      patients who excreted the ACV-resistant strains were treated with foscarnet
      (PFA), and 61% of them developed resistance to PFA. The collection of a large
      number of isolates enabled an evaluation of the prevalence of resistance of HSV
      strains to antiviral drugs to be made. This prevalence has remained stable over
      the last 10 years, as much among immunocompetent patients as among
      immunocompromised patients.

PMID- 14715761
TI  - Serotype 14 variants of the France 9V(-3) clone from Baltimore, Maryland, can be
      differentiated by the cpsB gene.
AB  - European serotype 14 variants of the France 9V(-3) clone, which have arisen
      through recombination events involving the penicillin binding protein 1a (pbp1a)
      gene, have cpsB sequences distinct from those of the 9V(-3) clone. Serotype 14
      variants of the 9V(-3) clone have not been compared to genetically diverse
      serotype 14 strains isolated from an entire metropolitan area in the United
      States. All serotype 14 non-penicillin-susceptible Streptococcus pneumoniae
      strains causing invasive disease in Baltimore, Md., from 1995 to 1996 were
      compared by using pulsed-field gel electrophoresis (PFGE), multilocus sequence
      typing (MLST), pbp1a PCR restriction profiles, and cpsB and pbp1a sequences. The
      cpsB genes from strains of 13 serotypes also were analyzed to assess the
      correlation with serotype. Twenty-seven percent (3 of 11) of the serotype 14
      strains were related by PFGE and MLST to the 9V(-3) clone. The serotype 14
      variants from Baltimore, unlike the European variants, were related neither to
      the 9V(-3) clone nor to the R6 strain from positions 1498 to 1710 of the pbp1a
      gene. All serotype 14 strains had cpsB sequences that differed by <or=1% (0 to 5
      of 476 bp) from each other and that were >or=16% (78 to 83 of 476 bp) divergent
      from that of the 9V(-3) clone. Allowing for a 2-bp difference in the cpsB
      sequence resulted in the highest correlation between the cpsB gene and serotype.
      Overall, 95% (84 of 88) of the strains were classified correctly by serotype with
      the cpsB sequence. The distal recombination site of the Baltimore serotype 14
      variants of the 9V(-3) clone was not identical to that of the European serotype
      14 variants. The cpsB gene was serotype specific regardless of whether capsular
      switching occurred. Although the correlation between serotype and the cpsB
      sequence was high, the overall diversity of the cpsB gene within a serotype
      likely will limit the role of this gene in a sequence-based serotyping method.

PMID- 14715762
TI  - Real-time reverse transcription loop-mediated isothermal amplification for rapid
      detection of West Nile virus.
AB  - A one-step, single tube, real-time accelerated reverse transcription loop
      mediated isothermal amplification (RT-LAMP) assay was developed for detecting the
      envelope gene of West Nile (WN) virus. The RT-LAMP assay is a novel method of
      gene amplification that amplifies nucleic acid with high specificity, efficiency,
      and rapidity under isothermal conditions with a set of six specially designed
      primers that recognize eight distinct sequences of the target. The whole
      procedure is very simple and rapid, and amplification can be obtained in less
      than 1 h by incubating all of the reagents in a single tube with reverse
      transcriptase and Bst DNA polymerase at 63 degrees C. Detection of gene
      amplification could be accomplished by agarose gel electrophoresis, as well as by
      real-time monitoring in an inexpensive turbidimeter. When the sensitivity of the
      RT-LAMP assay was compared to that of conventional RT-PCR, it was found that the
      RT-LAMP assay demonstrated 10-fold higher sensitivity compared to RT-PCR, with a
      detection limit of 0.1 PFU of virus. By using real-time monitoring, 10(4) PFU of
      virus could be detected in as little as 17 min. The specificity of the RT-LAMP
      assay was validated by the absence of any cross-reaction with other, closely
      related, members of the Flavivirus group, followed by restriction digestion and
      nucleotide sequencing of the amplified product. These results indicate that the
      RT-LAMP assay is extremely rapid, cost-effective, highly sensitive, and specific
      and has potential usefulness for rapid, comprehensive WN virus surveillance along
      with virus isolation and/or serology.

PMID- 14715763
TI  - Prevalence of Bartonella henselae in Italian stray cats: evaluation of serology
      to assess the risk of transmission of Bartonella to humans.
AB  - Bartonella henselae is the major etiological agent of cat scratch disease in
      humans. Cats act as the natural reservoir of B. henselae and can transmit the
      infection to humans by a bite or scratch. The prevalence of B. henselae in cat
      populations was evaluated by serological and bacteriological tests. A total of
      769 stray cats from three urban and three rural areas in northern Italy were
      sampled between January 1999 and December 2000. The positive and the negative
      predictive values of serological tests with respect to bacteremic status were
      evaluated. Tests of a total of 140 cats (18%) resulted in detection of
      bacteremia. A total of 540 cats were tested by serology; 207 (38%) were
      seropositive. Of the 531 cats tested by both methods, the results for 65 (12.2%)
      showed both bacteremia detection and seropositivity. The molecular typing of the
      isolates showed that 20.6% of bacteremic cats were infected with B. henselae type
      I strain, 61.1% were infected with B. henselae type II, and 18.3% were coinfected
      with both. A statistically significant difference in antibody and bacteremia
      prevalences among geographical areas was detected. Statistical analysis showed no
      association between characteristics such as seroprevalence-bacteremic status,
      sex, general health status, and the presence of ectoparasites. The negative
      predictive value of serological test was 84.7%, and the positive predictive value
      was 31.8%. Receiving operator characteristic analysis of the data showed that
      serological tests had a low predictive value in relation to the bacteremic status
      of a cat; in surveys aimed at assessing the real risk of B. henselae infection in
      a human population, therefore, we suggest the use of blood culture as the
      reference test. Nevertheless, both blood culture assays and serological tests for
      Bartonella infection should be performed for a complete evaluation of the health
      status of cats.

PMID- 14715764
TI  - Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum
      beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae
      clinical isolates tested by using NCCLS ESBL methodology.
AB  - Escherichia coli and Klebsiella pneumoniae isolates with extended-spectrum beta
      lactamases (ESBLs) or AmpC cephalosporinases generally respond as predicted to
      NCCLS tests for ESBL production. However, inoculum size may affect MICs. The
      effect of inoculum level in clinical isolates expressing beta-lactamases were
      studied at inocula within 0.5 log unit of the standard inoculum, using broth
      microdilution methodology with ceftazidime, cefotaxime, cefepime, cefpodoxime,
      and aztreonam. Strains with TEM-1 or no beta-lactamases gave consistent MIC
      results with inocula of 10(5) and 10(6) CFU/ml. When the bacteria were screened
      for ESBL production and the lower inoculum was used, several strains with ESBLs,
      including CTX-M-10, TEM-3, TEM-10, TEM-12, TEM-6, SHV-18, and K1, gave false
      negative results for one or more antimicrobial agents (MICs below the NCCLS
      screening concentration for detecting suspected ESBLs). When the higher inoculum
      was used, MICs of at least one antimicrobial agent increased at least fourfold in
      strains producing TEM-3, TEM-10, TEM-28, TEM-43, SHV-5, SHV-18, and K1. All
      antimicrobial agents showed an inoculum effect with at least one ESBL producer.
      Confirmatory clavulanate effects were seen for both inocula for all ESBL
      producing strains with all antimicrobial agents tested, except for the CTX-M-10
      producing E. coli with ceftazidime and the SHV-18-producing K. pneumoniae with
      cefotaxime. In kinetic studies, cefpodoxime and cefepime were hydrolyzed by ESBLs
      in a manner similar to that of cefotaxime. When total beta-lactamase activity and
      hydrolysis parameters were evaluated, however, no single factor was predictive of
      inoculum effects. These results indicate that the NCCLS screening and
      confirmation tests are generally predictive of ESBL production, but false
      negative results can arise when a lower inoculum is used in testing.

PMID- 14715765
TI  - Comparative analysis of multilocus sequence typing and pulsed-field gel
      electrophoresis for characterizing Listeria monocytogenes strains isolated from
      environmental and clinical sources.
AB  - One hundred seventy-five Listeria monocytogenes strains were characterized by
      serotyping, pulsed-field gel electrophoresis (PFGE), and multilocus sequence
      typing (MLST) based on loci in actA, betL, hlyA, gyrB, pgm, and recA. One hundred
      twenty-two sequence types (STs) were identified by MLST based on allelic profiles
      of the four housekeeping genes (betL, gyrB, pgm, and recA), and 34 and 38 alleles
      were identified for hlyA and actA, respectively. Several actA and hlyA alleles
      appeared to be predominantly associated with clinical isolates. MLST
      differentiated most of the L. monocytogenes strains better than did PFGE, and the
      discriminating ability of PFGE was better than that of serotyping. Several
      strains with different serotypes were found, by MLST and PFGE, to have very
      closely related genetic backgrounds, which suggested possible "antigen switching"
      among them. MLST can be a useful typing tool for differentiating L. monocytogenes
      strains (including strains undistinguishable by PFGE typing and serotyping), and
      it may be of value during investigations of food-borne outbreaks of listeriosis.

PMID- 14715766
TI  - Assessment of agreement between the AMPLICOR HIV-1 MONITOR test versions 1.0 and
      1.5.
AB  - The agreement of the microwell plate AMPLICOR HIV-1 MONITOR version 1.0 (MWP
      1.0), the microwell plate AMPLICOR HIV-1 MONITOR version 1.5 (MWP 1.5), and the
      COBAS AMPLICOR HIV-1 MONITOR version 1.5 (COBAS 1.5) tests was evaluated using
      clinical specimens and well-characterized control material. Two hundred patient
      plasma specimens and a panel of known human immunodeficiency virus type 1 (HIV-1)
      subtypes were tested. All data were log(10) transformed prior to analysis. The
      95% limits of agreement for the three tests at the average of 3.66 log(10)
      copies/ml were +/- 0.28 log(10), +/- 0.34 log(10), and +/- 0.34 log(10) copies/ml
      for MWP 1.0-MWP 1.5, MWP 1.0-COBAS 1.5, and MWP 1.5-COBAS 1.5, respectively. Ten
      specimens (6.1%) had differences exceeding the limits of agreement for the MWP
      1.0 and MWP 1.5 tests. Correlation coefficients among the three tests were high
      (r >or=0.96). The viral-load values obtained with the MWP 1.0 test were only 2.1%
      higher on average than those measured with the MWP 1.5 test and 1.6% higher than
      those seen with the COBAS 1.5 test. The MWP 1.5 test values were 0.8% higher than
      the COBAS 1.5 test values. Overall, there was less agreement among the different
      tests for viral-load values near the lower limit of quantification. The MWP 1.0
      test underquantified subtypes A, E, F, G, and H by 1.0 to 2.0 log(10) copies/ml;
      this problem was not observed with the MWP 1.5 test. The close agreement among
      the results obtained with the different test versions and formats suggests that
      it is not necessary to reestablish a baseline viral load when changing AMPLICOR
      HIV-1 MONITOR tests, unless the patient is known to be infected with a non-B
      subtype.

PMID- 14715767
TI  - Isolation of a fastidious Bergeyella species associated with cellulitis after a
      cat bite and a phylogenetic comparison with Bergeyella zoohelcum strains.
AB  - Bergeyella zoohelcum is an uncommon zoonotic pathogen typically associated with
      cat or dog bites. Previously, only five cases of B. zoohelcum infection have been
      reported. We report the isolation and characterization of a fastidious Bergeyella
      species from acute cellulitis in the upper extremity of a 60-year-old woman. The
      organism was too fastidious for identification and susceptibility testing with
      traditional culture methods. The isolate was characterized further by PCR
      amplification and sequencing of the 16S rRNA gene with broad-range eubacterial
      primers. Phylogenetic analysis of the 16S ribosomal DNA sequence indicated that
      this isolate was a member of the species B. zoohelcum (previously Weeksella
      zoohelcum), a gram-negative bacillus that is rarely associated with infections in
      humans. Despite sharing a close genetic relationship with other B. zoohelcum
      strains, this isolate was extremely fastidious in nature, raising the possibility
      that similar strains from cat or dog bite wound infections have been
      underreported.

PMID- 14715768
TI  - Utility of NCCLS guidelines for identifying extended-spectrum beta-lactamases in
      non-Escherichia coli and Non-Klebsiella spp. of Enterobacteriaceae.
AB  - NCCLS screening and confirmation methods for detecting extended-spectrum beta
      lactamases (ESBLs) apply only to Escherichia coli and Klebsiella spp., yet ESBLs
      have been found in other members of the family Enterobacteriaceae. We evaluated
      the effectiveness of NCCLS methods for detecting ESBLs in 690 gram-negative
      isolates of Enterobacteriaceae that excluded E. coli, Klebsiella pneumoniae, and
      Klebsiella oxytoca. Isolates were collected between January 1996 and June 1999
      from 53 U.S. hospitals participating in Project ICARE (Intensive Care
      Antimicrobial Resistance Epidemiology). The antimicrobial susceptibility patterns
      of the isolates were determined by using the NCCLS broth microdilution method
      (BMD), and those isolates for which the MIC of ceftazidime, cefotaxime,
      ceftriaxone, or aztreonam was >or=2 microg/ml or the MIC of cefpodoxime was >or=8
      microg/ml (positive ESBL screen test) were further tested for a clavulanic acid
      (CA) effect by BMD and the disk diffusion method (confirmation tests). Although
      355 (51.4%) of the isolates were ESBL screen test positive, only 15 (2.2%) showed
      a CA effect. Since 3 of the 15 isolates were already highly resistant to the five
      NCCLS indicator drugs, ESBL detection would have an impact on the reporting of
      only 1.7% of the isolates in the study. Only 6 of the 15 isolates that showed a
      CA effect contained a bla(TEM), bla(SHV), bla(CTX-M), or bla(OXA) beta-lactamase
      gene as determined by PCR (with a corresponding isoelectric focusing pattern).
      Extension of the NCCLS guidelines for ESBL detection to Enterobacteriaceae other
      than E. coli and Klebsiella spp. does not appear to be warranted in the United
      States at present, since the test has poor specificity for this population and
      would result in changes in categorical interpretations for only 1.7% of
      Enterobacteriaceae tested.

PMID- 14715769
TI  - Evaluation of a TaqMan PCR assay to detect rabies virus RNA: influence of
      sequence variation and application to quantification of viral loads.
AB  - Published assays that use TaqMan PCR are consistently sensitive, rapid, and
      readily transferable. Here we describe a TaqMan PCR-based method for the
      detection of rabies virus (RV) RNA in tissue samples. We show that the method has
      an acceptable linear range, is both sensitive and specific, and, importantly,
      correlates with the concentration of infectious virus. In addition, the levels of
      RV-specific amplification are adjustable according to the levels of an endogenous
      control (beta-actin mRNA), allowing the calculation of comparable quantities. We
      tested the capacity of this assay to cope with target sequence variations. The
      number of sequence mismatches between gene-specific oligonucleotides and the
      target sequence significantly affects amplification (P < 0.001), and point
      mutations at the center of the probe can result in false-negative results through
      the prevention of probe binding and subsequent fluorescence. This study
      demonstrates that the genetic heterogeneity of RVs may prove a serious obstacle
      in the development of a diagnostic assay based on TaqMan PCR; however, the
      quantification of RV levels may prove to be a valuable application of this assay.

PMID- 14715770
TI  - Molecular epidemiology of clinical isolates of methicillin-resistant
      Staphylococcus aureus in Taiwan.
AB  - During July 2000 and October 2001, a total of 595 clinical isolates of
      methicillin-resistant Staphylococcus aureus (MRSA) were collected from six
      medical centers distributed in northern, central, and southern Taiwan. Specimen
      sources included blood (n = 279), pus (n = 173), sputum (n = 94), body fluids (n
      = 21), catheter tips (n = 20), and urine (n = 8). Pulsed-field gel
      electrophoresis (PFGE) with SmaI digestion was used to fingerprint these
      isolates. A total of 31 genotypes with 97 type-subtypes were identified. Subtypes
      could be identified in 7 genotypes. While there were 6 to 15 genotypes in each
      hospital, 433 isolates (73%) were shown to belong to a major type (genotype A,
      with 29 subtypes). This genotype was not only the type prevailing in all six
      hospitals but also the predominant clone in each hospital, accounting for 46 to
      89% of all isolates in each hospital. Genotype C (16 subtypes) was the second
      dominant genotype, accounting for 9% of all isolates, and was distributed in five
      hospitals. Genotypes D (11 subtypes), E (5 subtypes), and B (6 subtypes) were
      distributed in five, four, and three hospitals, respectively. The other 26 types
      (30 type-subtypes) were minor. We conclude that the majority of MRSA clinical
      isolates shared a common PFGE pattern, indicating the presence of a single,
      epidemic MRSA clone prevailing in major hospitals in Taiwan.

PMID- 14715771
TI  - Serotypes, virulence genes, and intimin types of Shiga toxin (verotoxin)
      producing Escherichia coli isolates from human patients: prevalence in Lugo,
      Spain, from 1992 through 1999.
AB  - We have analyzed the prevalence of Shiga toxin-producing Escherichia coli (STEC)
      in stool specimens of patients with diarrhea or other gastrointestinal
      alterations from the Xeral-Calde Hospital of Lugo City (Spain). STEC strains were
      detected in 126 (2.5%) of 5,054 cases investigated, with a progressive increase
      in the incidence from 0% in 1992 to 4.4% in 1999. STEC O157:H7 was isolated in 24
      cases (0.5%), whereas non-O157 STEC strains were isolated from 87 patients
      (1.7%). STEC strains were (after Salmonella and Campylobacter strains) the third
      most frequently recovered enteropathogenic bacteria. A total of 126 human STEC
      isolates were characterized in this study. PCR showed that 43 (34%) isolates
      carried stx(1) genes, 45 (36%) possessed stx(2) genes and 38 (30%) carried both
      stx(1) and stx(2). A total of 88 (70%) isolates carried an ehxA enterohemolysin
      gene, and 70 (56%) isolates possessed an eae intimin gene (27 isolates with type
      gamma1, 20 with type beta1, 8 with type zeta, 5 with type gamma2, and 3 with type
      epsilon). STEC isolates belonged to 41 O serogroups and 66 O:H serotypes,
      including 21 serotypes associated with hemolytic uremic syndrome and 30 new
      serotypes not previously reported among human STEC strains in other studies.
      Although the 126 STEC isolates belonged to 81 different seropathotypes
      (associations between serotypes and virulence genes), only four accounted for 31%
      of isolates. Seropathotype O157:H7 stx(1) stx(2) eae-gamma1 ehxA was the most
      common (13 isolates) followed by O157:H7 stx(2) eae-gamma1 ehxA (11 isolates),
      O26:H11 stx(1) eae-beta1 ehxA (11 isolates), and O111:H- stx(1) stx(2) eae-gamma2
      ehxA (4 isolates). Our results suggest that STEC strains are a significant cause
      of human infections in Spain and confirm that in continental Europe, infections
      caused by STEC non-O157 strains are more common than those caused by O157:H7
      isolates. The high prevalence of STEC strains (both O157:H7 and non-O157 strains)
      in human patients, and their association with serious complications, strongly
      supports the utilization of protocols for detection of all serotypes of STEC in
      Spanish clinical microbiology laboratories.

PMID- 14715772
TI  - Use of real-time PCR to resolve slide agglutination discrepancies in serogroup
      identification of Neisseria meningitidis.
AB  - Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia
      in children and young adults in the United States. Rapid and reliable
      identification of N. meningitidis serogroups is crucial for judicious and
      expedient response to cases of meningococcal disease, including decisions about
      vaccination campaigns. From 1997 to 2002, 1,298 N. meningitidis isolates,
      collected in the United States through the Active Bacterial Core surveillance
      (ABCs), were tested by slide agglutination serogrouping (SASG) at both the ABCs
      sites and the Centers for Disease Control and Prevention (CDC). For over 95% of
      isolates, SASG results were concordant, while discrepant results were reported
      for 58 isolates. To resolve these discrepancies, we repeated the SASG in a
      blinded fashion and employed ctrA and six serogroup-specific PCR assays (SGS-PCR)
      to determine the genetic capsule type. Seventy-eight percent of discrepancies
      were resolved, since results of the SGS-PCR and SASG blinded study agreed with
      each other and confirmed the SASG result at either state health laboratories or
      CDC. This study demonstrated the ability of SGS-PCR to efficiently resolve SASG
      discrepancies and identified the main cause of the discrepancies as overreporting
      of these isolates as nongroupable. It also reemphasized the importance of
      adherence to quality assurance procedures when performing SASG and prompted
      prospective monitoring for SASG discrepancies involving isolates collected
      through ABCs in the United States.

PMID- 14715773
TI  - Development of a real-time reverse-transcription PCR for detection of newcastle
      disease virus RNA in clinical samples.
AB  - A real-time reverse-transcription PCR (RRT-PCR) was developed to detect avian
      paramyxovirus 1 (APMV-1) RNA, also referred to as Newcastle disease virus (NDV),
      in clinical samples from birds. The assay uses a single-tube protocol with
      fluorogenic hydrolysis probes. Oligonucleotide primers and probes were designed
      to detect sequences from a conserved region of the matrix protein (M) gene that
      recognized a diverse set (n = 44) of APMV-1 isolates. A second primer-probe set
      was targeted to sequences in the fusion protein (F) gene that code for the
      cleavage site and detect potentially virulent NDV isolates. A third set, also
      directed against the M gene, was specific for the North American (N.A.) pre-1960
      genotype that includes the common vaccine strains used in commercial poultry in
      the United States. The APMV-1 M gene, N.A. pre-1960 M gene, and F gene probe sets
      were capable of detecting approximately 10(3), 10(2), and 10(4) genome copies,
      respectively, with in vitro-transcribed RNA. Both M gene assays could detect
      approximately 10(1) 50% egg infective doses (EID(50)), and the F gene assay could
      detect approximately 10(3) EID(50). The RRT-PCR test was used to examine clinical
      samples from chickens experimentally infected with the NDV strain responsible for
      a recent epizootic in the southwestern United States. Overall, a positive
      correlation was obtained between the RRT-PCR results and virus isolation for NDV
      from clinical samples.

PMID- 14715774
TI  - Novel mass spectrometry-based tool for genotypic identification of mycobacteria.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) after base-specific cleavage of PCR amplified and in vitro
      transcribed 16S rRNA gene (rDNA) was used for the identification of mycobacteria.
      Full-length 16S rDNA reference sequences of 12 type strains of Mycobacterium spp.
      frequently isolated from clinical specimens were determined by PCR, cloning, and
      sequencing. For MALDI-TOF MS-based comparative sequence analysis, mycobacterial
      16S rDNA signature sequences ( approximately 500 bp) of the 12 type strains and
      24 clinical isolates were PCR amplified using RNA promoter-tagged forward
      primers. T7 RNA polymerase-mediated transcription of forward strands in the
      presence of 5-methyl ribo-CTP maximized mass differences of fragments generated
      by base-specific cleavage. In vitro transcripts were subsequently treated with
      RNase T1, resulting in G-specific cleavage. Sample analysis by MALDI-TOF MS
      showed a specific mass signal pattern for each of the 12 type strains, allowing
      unambiguous identification. All 24 clinical isolates were identified
      unequivocally by comparing their detected mass signal pattern to the reference
      sequence-derived in silico pattern of the type strains and to the in silico mass
      patterns of published 16S rDNA sequences. A 16S rDNA microheterogeneity of the
      Mycobacterium xenopi type strain (DSM 43995) was detected by MALDI-TOF MS and
      later confirmed by Sanger dideoxy sequencing. In conclusion, analysis of 16S rDNA
      amplicons by MS after base-specific cleavage of RNA transcripts allowed fast and
      reliable identification of the Mycobacterium tuberculosis complex and ubiquitous
      mycobacteria (mycobacteria other than tuberculosis). The technology delivers an
      open platform for high-throughput microbial identification on the basis of any
      specific genotypic marker region.

PMID- 14715775
TI  - Detection of severe acute respiratory syndrome coronavirus in blood of infected
      patients.
AB  - Severe acute respiratory syndrome (SARS) has caused major outbreaks worldwide,
      resulting in an urgent need to obtain sensitive and accurate diagnosis of this
      disease. PCR-based detection methods were developed for use on a variety of
      samples, including blood. Eighteen subjects were investigated, and results
      indicated that blood samples contain sufficient virus for detection by using
      quantitative real-time PCR.

PMID- 14715776
TI  - Rapid immunochromatographic test using recombinant SAG2 for detection of
      antibodies against Toxoplasma gondii in cats.
AB  - An immunochromatographic test using recombinant truncated surface antigen 2 for
      detection of antibodies against Toxoplasma gondii was developed. Evaluation of
      detection of the antibody in mice and cats suggests that this test is rapid,
      simple, accurate, relatively inexpensive, and suitable for use under field
      conditions.

PMID- 14715777
TI  - Nissui glucose fermentative gram-negative rod identification system EB-20 gives a
      unique profile for typical non-sorbitol-fermenting Escherichia coli O157:H7.
AB  - The 98 non-sorbitol-fermenting (NSF) Escherichia coli O157:H7 strains identified
      on a Nissui glucose fermentative gram-negative rod identification system (EB-20)
      gave a unique biochemical profile number that was not detected in 85 pathogenic
      and 13 nonpathogenic E. coli strains. Thus, EB-20 is useful for the
      identification of NSF E. coli O157:H7 and provides a simple, cost-effective, and
      reliable tool for clinical laboratories.

PMID- 14715778
TI  - Development of an immunochromatographic test with recombinant EMA-2 for the rapid
      detection of antibodies against Babesia equi in horses.
AB  - An immunochromatographic test (BeICT) for the rapid detection of antibodies
      against Babesia equi was developed. It clearly differentiated B. equi-infected
      horses from B. caballi-infected and uninfected horses. The agreement with enzyme
      linked immunosorbent assay results was 96.7% in the detection of field sera. The
      results suggest that BeICT is rapid, simple, reliable, and suitable for use to
      detect B. equi infection in the field.

PMID- 14715779
TI  - Possible high rate of transmission of nontypeable Haemophilus influenzae,
      including beta-lactamase-negative ampicillin-resistant strains, between children
      and their parents.
AB  - The possible transmission of nontypeable Haemophilus influenzae between children
      and their parents was evaluated in 18 pairs of subjects from 15 families. Of the
      33 isolates, 31 were found to be beta-lactamase negative, including 10 beta
      lactamase-negative, ampicillin (AMP)-resistant (BLNAR) strains (AMP MIC, >or=1.0
      microg/ml) and 2 were beta-lactamase producing. Molecular typing by pulsed-field
      gel electrophoresis (PFGE) showed that 10 BLNAR isolates had 6 patterns, 23 non
      BLNAR isolates had 13 patterns, and these patterns were different from each
      other, except for 1 pattern. As a result, the PFGE patterns in 14 of 18 pairs
      were indistinguishable and those in 4 pairs were different. These data indicate a
      possible high rate of intrafamilial transmission of nontypeable H. influenzae,
      including BLNAR strains, between children and their parents.

PMID- 14715780
TI  - Method for testing for human papillomavirus infection in patients with cervical
      intraepithelial disease.
AB  - To determine whether DNA detection of high-risk human papillomavirus could
      represent a reliable screening technique and a useful follow-up method, we
      investigated the performance of the Hybrid Capture II assay in detecting high
      grade cervical lesions. The test positivity at 1.86 pg/ml had a high sensitivity
      (94.7%) and improved specificity. It was also a suitable follow-up method for
      detecting the recurrence of cervical intraepithelial disease in patients.

PMID- 14715781
TI  - Amplified fragment length polymorphism fingerprinting is an effective technique
      to distinguish streptococcus pneumoniae from other Streptococci and an efficient
      alternative to pulsed-field gel electrophoresis for molecular typing of
      pneumococci.
AB  - Amplified fragment length polymorphism versus pulsed-field gel electrophoresis
      was used for fingerprinting of 85 macrolide-resistant pneumococcal isolates
      identified by using primarily phenotypic methods. Confirmation of identification
      by 16S rRNA sequencing revealed that 27 isolates were actually nonpneumococci.
      Amplified fragment length polymorphism but not pulsed-field gel electrophoresis
      offered simultaneous and accurate discrimination between pneumococci and
      nonpneumococcal species.

PMID- 14715782
TI  - PCR-based genotyping of Mycobacterium tuberculosis with new GC-rich repeated
      sequences and IS6110 inverted repeats used as primers.
AB  - In the present study we attempted to develop a PCR-based epidemiological tool for
      the differentiation of Mycobacterium tuberculosis isolates. Use of the designed
      primers Mtb1 (5'-CCG-GCG-GGG-CCG-GCG-G) and Mtb2 (5'-CGG-CGG-CAA-CGG-CGG-C)
      targeting frequently repeated 16-bp sequences in combination with primers sited
      at the inverted repeats flanking IS6110 allowed differentiation of M.
      tuberculosis isolates.

PMID- 14715783
TI  - Improving the bacteriological diagnosis of tuberculous meningitis.
AB  - We made a bacteriological diagnosis of tuberculous meningitis in 107 of 132 (81%)
      adults with clinical tuberculous meningitis: acid-fast bacilli were seen in 77 of
      132 (58%) and cultured from 94 of 132 (71%). Volume of cerebrospinal fluid,
      duration of symptoms, cerebrospinal fluid neutrophils, lactate, and glucose were
      all independently associated with bacteriological confirmation.

PMID- 14715784
TI  - Evaluation of the NCCLS M44-P disk diffusion method for determining
      susceptibilities of 276 clinical isolates of Cryptococcus neoformans to
      fluconazole.
AB  - We evaluated the NCCLS M44-P fluconazole disk diffusion method in comparison with
      the NCCLS M27-A2 broth microdilution method for determining the susceptibility of
      276 isolates of Cryptococcus neoformans. Disk diffusion testing was performed
      using Mueller-Hinton agar supplemented with 2% glucose and 0.5 microg of
      methylene blue/ml. Among the 276 isolates, 259 (93.8%) were susceptible, 16
      (5.8%) were susceptible--dose dependent, and 1 (0.4%) was resistant to
      fluconazole as determined by the NCCLS broth microdilution method. The overall
      categorical agreement between the two methods was 86%, with 0% very major errors,
      2% major errors, and 12% minor errors. The disk diffusion method using Mueller
      Hinton agar supplemented with glucose and methylene blue appears to be a useful
      approach for determining the fluconazole susceptibility of C. neoformans.

PMID- 14715785
TI  - Helicobacter species in the intestinal mucosa of patients with ulcerative
      colitis.
AB  - In a search for Helicobacter species in the intestinal mucosae of 42 patients
      with ulcerative colitis (UC) and 74 without UC, only H. pylori was found.
      Although the bacterium was detected in UC patients by culture (7.1%) and nested
      PCR (19.0%), its presence was not associated with the disease (P = 0.13).

PMID- 14715786
TI  - Susceptibilities to different antibiotics of Helicobacter pylori strains isolated
      from patients at the pediatric medical center of Tehran, Iran.
AB  - Antibiotic susceptibility testing of 70 pediatric Helicobacter pylori isolates
      was performed by using screening agar and disk diffusion methods. Resistance to
      metronidazole and tinidazole was 72 to 79% and 71 to 81% by modified disk
      diffusion and 77% and 78% by screening agar, respectively. Susceptibilities to
      amoxicillin, ampicillin, clarithromycin, tetracycline, erythromycin, and
      ciprofloxacin were 58, 69, 75, 68, 68, and 65%, respectively.

PMID- 14715787
TI  - Mutations including IS6110 insertion in the gene encoding the MPB64 protein of
      Capilia TB-negative Mycobacterium tuberculosis isolates.
AB  - A simple immunochromatographic assay, Capilia TB, using anti-MPB64 monoclonal
      antibodies, is a kit for discriminating between the Mycobacterium tuberculosis
      complex and mycobacteria other than tubercle bacilli. The sensitivity of the kit
      was estimated to be 99.2% (381 of 384 samples). The sequencing analysis revealed
      that all of the Capilia TB-negative isolates had mutations within the mpb64 gene,
      leading to the production of an incomplete protein as a result of a deletion of
      the C-terminal region of the protein.

PMID- 14715788
TI  - Eight-year survey of human rotavirus strains demonstrates circulation of unusual
      G and P types in Hungary.
AB  - Between 1992 and 2000, a total of 4173 rotavirus-positive samples were collected
      from two areas of Hungary. Of these, 2020 specimens (48.4%) were analyzed for G
      serotype, using monoclonal antibody-based immunoassay and reverse transcription
      PCR. By the two methods, 1789 samples were specified as G1 (62%), G2 (12.2%), G3
      (1.4%), G4 (6.4%), G6 (1.0%), G9 (2.9%), or mixed infection (2.6%), and the
      remaining 231 (11.4%) could not be G typed. The linkage between G and P type,
      subgroup specificity, and RNA profile was investigated with a sample subset.
      Among these specimens, we identified both the four globally common strains
      (P[8],G1 subgroup II (sgII); P[4],G2 sgI; P[8],G3 sgII; and P[8],G4 sgII) and six
      uncommon strains (P[6],G4 sgII; P[9],G3 sgI; P[9],G6 sgI; P[14],G6 sgI; P[8],G9
      sgII; and P[8],G9 sgI). All strains with P[8], P[6], P[9], and P[14]
      specificities had a long electropherotype, whereas most of those carrying a P[4]
      specificity were associated with a short electropherotype. Although once
      considered to be rare, P[9],G6 and P[8],G9 rotavirus strains represent
      potentially important new serotypes in Hungary.

PMID- 14715789
TI  - Reduced etiological role for enteropathogenic Escherichia coli in cases of
      diarrhea in Brazilian infants.
AB  - Previously common in Brazil, enteropathogenic Escherichia coli (EPEC) strains of
      serogroups O55, O111, and O119 are now rare, while enteroadherent strains other
      than EPEC, belonging to serogroups such as O125, were prevalent among 126
      diarrheic infants less than 1 year old who were surveyed. None of these strains
      had the EPEC bundle-forming pilus (bfpA) gene.

PMID- 14715790
TI  - Use of genome selected repeated sequences increases the sensitivity of PCR
      detection of Tropheryma whipplei.
AB  - The availability of the Tropheryma whipplei genome offers the putative
      possibility of choosing logical DNA targets. We applied a PCR assay (targeting
      repeated sequences of T. whipplei) to samples from patients with Whipple's
      disease and to those from members of a control group. When compared to the
      results seen with regular PCR, the sensitivity of repeat PCR was significantly
      enhanced (P = 0.02) without alteration of its specificity.

PMID- 14715791
TI  - Specific oligonucleotide primers for identification of Cladophialophora
      carrionii, a causative agent of chromoblastomycosis.
AB  - Cladophialophora carrionii is one of the relatively common causative agents of
      chromoblastomycosis. We have developed the specific oligonucleotide primer set
      based on the internal transcribed spacer regions of ribosomal DNA for the rapid
      identification of this pathogen. PCR with this primer set amplified a 362-bp
      amplicon from C. carrionii strains. From other relevant dematiaceous species,
      including medically important dematiaceous fungi, such as Fonsecaea pedrosoi,
      Phialophora verrucosa, and Exophiala dermatitidis, and eight species of medically
      important yeasts, such as Candida albicans and Cryptococcus neoformans var.
      neoformans, the primer set did not produce any amplicon. PCR with this primer set
      may be a useful tool for the identification of C. carrionii.

PMID- 14715792
TI  - Impact of DNA polymerases and their buffer systems on quantitative real-time PCR.
AB  - An investigation of the influence of five DNA polymerase-buffer systems on real
      time PCR showed that the choice of both DNA polymerase and the buffer system
      affected the amplification efficiency as well as the detection window. The
      analytical repeatability of the data for different systems changed clearly,
      leading us to conclude that basing quantitative measurements on single-data-set
      standard curves can lead to significant errors.

PMID- 14715793
TI  - Survival of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis frozen in skim milk- tryptone-glucose-glycerol medium.
AB  - In STGG (skim milk, tryptone, glucose, glycerol) medium at -80 degrees C,
      Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis
      isolates survived for at least 3 years, and the same species have survived in
      nasopharyngeal swabs for at least 1.5 years. At -20 degrees C, S. pneumoniae and
      M. catarrhalis survived for 1.5 years, but H. influenzae survived for only 2
      months.

PMID- 14715794
TI  - Prevalence and antimicrobial susceptibility of serogroup D nontyphoidal
      Salmonella in a university hospital in Taiwan.
AB  - The incidence of serogroup D Salmonella has been increasing in Taiwan. Most of
      these isolates belonged to Salmonella enterica serovar Enteritidis and showed a
      relatively higher rate of resistance to sulfamethoxazole-trimethoprim than to
      other antimicrobial agents. The results of molecular experiments indicated that
      genes responsible for the resistance were located on plasmids. The resistance may
      occur via horizontal gene transfer. Furthermore, the first identification of
      ciprofloxacin and ceftriaxone resistance in serogroup D Salmonella in our
      hospital is also than they did to other antimicrobial agents cause for concern.

PMID- 14715795
TI  - Evaluation of four commercial test systems for identification of actinomyces and
      some closely related species.
AB  - We evaluated four commercially available kits for rapid identification of
      Actinomyces and related species. The kits identified correctly 26 to 65% of
      "classical" Actinomyces strains to the species level and 13 to 49% of newly
      described Actinomyces strains to the genus level, thus indicating relatively poor
      applicability and a need to update these kits.

PMID- 14715796
TI  - Strengths and limitations of commercial tests for hepatitis C virus RNA
      quantification.
AB  - The sensitivity of the Roche COBAS Monitor v.2.0 test was slightly better than
      that of the Bayer bDNA 3.0 test, but the Monitor test underquantified specimens
      by 2.5- to 10.6-fold even at relatively low hepatitis C virus RNA concentrations.
      Dilution prior to assay minimally decreased the reproducibility of the Monitor
      assay, leading to the recommendation for all specimens to be diluted 1:100 prior
      to testing by this assay.

PMID- 14715798
TI  - Molecular epidemiology of disease due to Mycobacterium bovis in humans in the
      United Kingdom.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis, with a wide
      host range. Fifty human M. bovis isolates were typed using spoligotyping and
      variable number tandem repeats (VNTR). Fifteen of these spoligotypes have not yet
      been recorded in cattle. The predominant spoligotype in humans and cattle was
      subdivided by VNTR.

PMID- 14715797
TI  - Prevalence of human immunodeficiency virus drug resistance mutations and subtypes
      in drug-naive, infected individuals in the army health service of Rio de Janeiro,
      Brazil.
AB  - The prevalence of mutations that confer resistance to antiretroviral drugs was
      examined in 56 drug-naive, human immunodeficiency virus type 1 (HIV-1)-infected
      individuals from the Army Health Service in Rio de Janeiro, Brazil. No primary
      protease inhibitor mutations were found, but secondary mutations were observed in
      51.2% of the samples. Fourteen percent of the viruses had reverse transcriptase
      inhibitor-associated mutations. Comparative analysis of protease secondary
      mutations from four different time periods in drug-naive patients in the city of
      Rio de Janeiro has indicated constant rates for particular mutations. Changes in
      CD4 cell counts and HIV viral load over time in subtype B- and non-B-infected
      drug-naive patients were not significantly different.

PMID- 14715799
TI  - Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay
      for diagnosis of invasive aspergillosis in liver transplant recipients.
AB  - The utility of galactomannan antigen for diagnosing invasive aspergillosis was
      evaluated in 154 liver transplant recipients. Sample agreement was 98.5%, and
      patient specificity was 87%. Galactomannan positivity correlated with mortality,
      even when controlled for the number of tests performed. Whether galactomannan
      positivity identifies a subgroup at risk for poor outcome warrants further
      evaluation.

PMID- 14715800
TI  - Automated procedure for improving the RNA isolation step in viral load testing
      for human immunodeficiency virus.
AB  - An automated RNA isolation procedure on the Qiagen BioRobot is described for
      performing viral load tests for human immunodeficiency virus (HIV) with the
      Amplicor HIV type 1 test. The new procedure improves the precision of the assay
      and requires significantly less labor than the presently used manual RNA
      isolation procedure.

PMID- 14715801
TI  - Detection of an unusual human rotavirus strain with G5P[8] specificity in a
      Cameroonian child with diarrhea.
AB  - Rotavirus strains detected as part of ongoing strain surveillance in Cameroon,
      and whose first-round reverse transcription-PCR product could not be genotyped by
      using conventional genotyping primers, were subjected to sequence analysis for
      strain characterization. We detected for the first time in Africa a human
      rotavirus with G5 specificity. The Cameroonian G5 strain had a short
      electrophoretic pattern and was of VP6 subgroup I specificity and a VP4 P[8]
      type. The VP7 gene shared a higher nucleic acid and amino acid homology with the
      porcine G5 strain CC117 (90 and 96%, respectively) than with human G5 strain IAL
      28 (86 and 92%, respectively). Phylogenetic analysis showed Cameroonian strain
      MRC3105 clustered together in the same lineage as two other reported porcine G5
      strains. The Cameroonian G5 strain, the first to be reported in humans outside of
      Latin America, may be a natural reassortant between animal and human rotavirus
      strains.

PMID- 14715802
TI  - Antimicrobial susceptibility and epidemiology of a worldwide collection of
      Chryseobacterium spp: report from the SENTRY Antimicrobial Surveillance Program
      (1997-2001).
AB  - Limited data are available on Chryseobacterium spp. leading to an evaluation of
      the patient demographics and susceptibility patterns for Chryseobacterium spp.
      collected in the first 5 years of the SENTRY Antimicrobial Surveillance Program
      (1997 to 2001). Fifty isolates (24 Chryseobacterium meningosepticum, 20
      Chryseobacterium indologenes, two Chryseobacterium gleum, and 4 Chryseobacterium
      spp. isolates) were collected. The highest Chryseobacterium prevalence was
      detected among the elderly. The most active antimicrobials were the newer
      quinolones (garenoxacin, gatifloxacin, and levofloxacin, each with a MIC at which
      90 percent of the isolates are inhibited [MIC(90)] of 1 micro g/ml and 98.0%
      susceptibility) followed by rifampin (MIC(90), 2 microg/ml and 85.7%
      susceptibility). Trimethoprim-sulfamethoxazole, ciprofloxacin, and piperacillin
      tazobactam also showed reasonable activity; vancomycin showed poor potency.

PMID- 14715803
TI  - Serodiagnosis of chronic and acute Chagas' disease with Trypanosoma cruzi
      recombinant proteins: results of a collaborative study in six Latin American
      countries.
AB  - An enzyme-linked immunosorbent assay to diagnose Chagas' disease by a serological
      test was performed with Trypanosoma cruzi recombinant antigens (JL8, MAP, and
      TcPo). High sensitivity (99.4%) and specificity (99.3%) were obtained when JL8
      was combined with MAP (JM) and tested with 150 serum samples from chagasic and
      142 nonchagasic individuals. Moreover, JM also diagnosed 84.2% of patients in the
      acute phase of T. cruzi infection.

PMID- 14715804
TI  - Development of a single-tube, cell lysis-based, genus-specific PCR method for
      rapid identification of mycobacteria: optimization of cell lysis, PCR primers and
      conditions, and restriction pattern analysis.
AB  - A single-tube PCR method was developed for efficient identification of
      nontuberculous mycobacteria (NTM) and their environmental isolates in about 3 h
      without conventional DNA isolation. The following three steps were optimized or
      developed: (i). a simple, 6-min direct cell lysis protocol as a PCR prestep for
      generation of DNA-template, (ii). an improved Mycobacterium-specific PCR
      amplification protocol with a broader species specificity using newly designed
      primers targeting a 228-bp region of the 65-kDa heat shock protein (hsp) gene and
      optimal PCR amplification conditions, and (iii). a genus-specific restriction
      analysis of the PCR product for conclusive identification of the unknown NTM
      isolates.

PMID- 14715805
TI  - Clinical and environmental distributions of Legionella strains in France are
      different.
AB  - In France, the clinical distribution of Legionella species and serogroups does
      not correspond to their environmental distribution. Legionella pneumophila
      serogroup 1 is more prevalent among clinical isolates (95.4%) than in the
      environment (28.2%), whereas L. anisa is more frequent in the environment (13.8%)
      than in the clinical setting (0.8%).

PMID- 14715807
TI  - Comparison of diagnostic sensitivities of three assays (Bartels enzyme
      immunoassay [EIA], Biotest EIA, and Binax NOW immunochromatographic test) for
      detection of Legionella pneumophila serogroup 1 antigen in urine.
AB  - The Bartels enzyme immunoassay (EIA), Biotest EIA, and Binax NOW
      immunochromatographic test (ICT) urinary antigen kits for the detection of
      Legionella pneumophila serogroup 1 were compared using 178 frozen urine samples.
      When nonconcentrated urine samples were used, the sensitivity levels of both
      enzyme EIAs were significantly higher than the sensitivity level of the ICT
      (Bartels EIA, 71.3%; Biotest EIA, 65.1%; Binax NOW ICT, 37% [P < 0.001]). After
      concentration of the urine samples, no significant differences in sensitivity
      were found among the three tests.

PMID- 14715806
TI  - Genetic diversity and population structure of Mycobacterium tuberculosis in
      Casablanca, a Moroccan city with high incidence of tuberculosis.
AB  - Although lower-resource countries have by far the highest burden of tuberculosis,
      knowledge of Mycobacterium tuberculosis population structure and genetic
      diversity in these regions remains almost nonexistent. In this paper, 150
      Moroccan M. tuberculosis isolates circulating in Casablanca were genotyped by
      random amplified polymorphic DNA analysis using 10 different primers and by
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      typing at 12 loci. The population genetic tests revealed a basically clonal
      structure for this population, without excluding rare genetic exchanges. Genetic
      analysis also showed a notable genetic polymorphism for the species M.
      tuberculosis, a weak cluster individualization, and an unexpected genetic
      diversity for a population in such a high-incidence community. Phylogenetic
      analyses of this Moroccan sample also supported that these isolates are
      genetically heterogeneous.

PMID- 14715808
TI  - Identification and molecular characterization of beta-hemolytic streptococci
      isolated from harbor seals (Phoca vitulina) and grey seals (Halichoerus grypus)
      of the German North and Baltic Seas.
AB  - Bacteriological investigations of seals of the German North and Baltic seas
      resulted in the isolation of bacteria of the genus Streptococcus belonging to
      Lancefield's serological groups C, F, and L. According to biochemical,
      serological, and 16S ribosomal DNA analysis, the group C and group F streptococci
      were identified as Streptococcus phocae. The group L streptococci could be
      classified as Streptococcus dysgalactiae subsp. dysgalactiae.

PMID- 14715809
TI  - Transfer of a Mycobacterium tuberculosis genotyping method, Spoligotyping, from a
      reverse line-blot hybridization, membrane-based assay to the Luminex multianalyte
      profiling system.
AB  - Spoligotyping using Luminex technology was shown to be a highly reproducible
      method suitable for high-throughput analysis. Spoligotyping of 48 isolates using
      the traditional membrane-based assay and the Luminex assay yielded concordant
      results for all isolates. The Luminex platform provides greater flexibility and
      cost effectiveness than the membrane-based assay.

PMID- 14715810
TI  - Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient.
AB  - Disseminated infection with the coelomycetous fungus Nattrassia mangiferae is a
      very rare disease affecting only the immunocompromised host. We report the first
      case of a disseminated infection with spondylodiscitis and granular skin lesions
      due to N. mangiferae in a renal transplant patient.

PMID- 14715811
TI  - First report of a case of meningitis caused by Cryptococcus adeliensis in a
      patient with acute myeloid leukemia.
AB  - Cryptococcus adeliensis is a recently described new fungal species which has been
      isolated from decaying algae in Terre Adelie, Antarctica. We report the first
      known case of meningitis caused by C. adeliensis in a patient with acute myeloid
      leukemia undergoing allogeneic peripheral blood stem cell transplantation.

PMID- 14715812
TI  - Osteosynthesis-associated bone infection caused by a nonproteolytic, nontoxigenic
      Clostridium botulinum-like strain.
AB  - A nonproteolytic, nontoxigenic Clostridium botulinum strain identified by
      conventional and molecular techniques as type B-, E-, or F-like (BEF-like) was
      isolated from a human postsurgical wound. All previous reports of such strains
      have been from environmental sources. Since toxin production is the main
      taxonomic denominator for C. botulinum, a new name is needed for nonproteolytic,
      nontoxigenic BEF-like clinical isolates.

PMID- 14715813
TI  - Disseminated mucormycosis in a patient with acute myeloblastic leukemia
      misdiagnosed as infection by Enterococcus faecium.
AB  - Mucormycosis is a rare complication in cancer patients. This report presents the
      case of a acute myeloblastic leukemia patient who developed an ascending
      paralysis due to disseminated mucormycosis. The presentation was unusual because
      the early symptoms were fever and pain, and the disease was misdiagnosed because
      of a concomitant infection by Enterococcus faecium.

PMID- 14715814
TI  - Quality control parameters for broth microdilution tests of anidulafungin.

PMID- 14715816
TI  - Free insulin-like growth factor (IGF) in disorders of IGF binding protein 3
      complex formation.

PMID- 14715817
TI  - GCMB--another serendipitous gift from evolution to clinical investigators.

PMID- 14715818
TI  - Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas
      indicates their parathyroid cell origin.
AB  - GCMA and GCMB are related transcription factors that are critically important for
      embryological development of the placenta and parathyroid glands, respectively.
      Mice in which parathyroid glands have been surgically removed or fail to develop
      due to genetic loss of GCMB show continued production of PTH from a subset of
      thymic cells that express GCMA. In this study we examined whether human thymus
      produces PTH and/or GCMA and whether intrathymic PTH-secreting adenomas express
      GCMA or GCMB to determine the embryological origin of the secretory cells. By
      contrast to mouse thymus, analysis of 22 samples of human thymus tissue by RT-PCR
      and/or immunohistochemistry failed to demonstrate the expression of either PTH or
      GCMA. RT-PCR analysis of 16 intrathymic adenomas from patients with surgically
      cured primary hyperparathyroidism showed that these tumors expressed PTH and GCMB
      and not GCMA. We conclude that the normal human thymus does not express GCMA or
      PTH, and therefore, in contrast to the mouse, the human thymus is not a source of
      PTH production. Finally, intrathymic PTH-secreting adenomas express the
      parathyroid-specific GCMB gene, which suggests that these tumors were derived
      from parathyroid cells that migrated errantly during embryogenesis.

PMID- 14715819
TI  - Orbital radiotherapy for Graves' ophthalmopathy.

PMID- 14715820
TI  - A randomized controlled trial of orbital radiotherapy versus sham irradiation in
      patients with mild Graves' ophthalmopathy.
AB  - Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been
      doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy.
      In a double-blind randomized trial, 44 patients received orbital irradiation, and
      44 were sham-irradiated. The primary outcome was assessed using major and minor
      criteria. As secondary outcome, we used a disease-specific quality of life
      questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up
      treatment. The primary outcome was successful in 23 of 44 (52%) irradiated
      patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment
      (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy
      was effective in improving eye muscle motility and decreasing the severity of
      diplopia. However, quality of life improved similarly in both groups. In the
      radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of
      the patients needed further treatment (P = 0.049). Retrobulbar irradiation did
      not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated
      and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment
      in mild ophthalmopathy. However, the improvement upon irradiation may not be
      associated with an increase in quality of life or a reduction in treatment costs.

PMID- 14715821
TI  - Metabolic bone disease in human immunodeficiency virus-infected children.

PMID- 14715822
TI  - Longitudinal changes of bone mineral density and metabolism in antiretroviral
      treated human immunodeficiency virus-infected children.
AB  - Highly active antiretroviral therapy (HAART) may be a contributory factor for a
      decreased bone mass and altered bone metabolism in HIV-infected children.
      However, the evolution of bone mineral density (BMD) and bone metabolism during
      HAART has not been studied yet. In the current longitudinal study we monitored
      the changes of BMD and bone metabolism over a period of 12 months. Thirty-two HIV
      infected children (15 girls and 17 boys), aged from 6.3 to 17.7 yr, with a long
      duration of HAART exposure (40.0 months at baseline) were enrolled in the study.
      As a control group, 381 healthy volunteers of comparable age were assessed. BMD
      was measured at the lumbar spine and whole skeleton by dual-energy x-ray
      absorptiometry. Bone-specific alkaline phosphatase (BALP, as bone formation
      index) and N-terminal telopeptide of type I collagen (as bone resorption index)
      were measured in serum and urine, respectively. BMD values at baseline were
      significantly lower at all skeletal sites than those of control subjects. The
      annual increment of spine BMD was comparable to normal, whereas that of the whole
      skeleton was significantly lower (P < 0.04). BALP and N-terminal telopeptide of
      type I collagen concentrations were significantly higher compared with controls
      at baseline and at follow-up. BALP annual changes of HIV patients were
      significantly different from normal. Our data confirm the presence of low BMD and
      bone metabolism derangement in HIV-infected children treated with HAART. The role
      of possible therapeutic approach to restore bone mass and metabolism should be
      assessed in pediatrics.

PMID- 14715823
TI  - Molecular detection of thyroid cancer: differentiating "signal" and "noise" in
      clinical assays.

PMID- 14715824
TI  - Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents
      its use in the follow-up of differentiated thyroid cancer patients.
AB  - Thyroglobulin (Tg) is a glycoprotein specifically synthesized by follicular
      thyroid epithelium. After thyroidectomy and remnant (131)I ablation, serum Tg is
      a specific and sensitive marker for the presence of thyroid cancer tissue, and
      its measurement is fundamental in the follow-up of patients affected by
      differentiated thyroid carcinomas (DTCs), being even more sensitive than
      diagnostic whole-body scan. Unfortunately, serum Tg measurement becomes useless
      in approximately 15-25% of DTC cases who are positive for anti-Tg antibodies that
      interfere with the Tg measurement. In these cases, Tg mRNA measurement has been
      proposed as an alternative to serum Tg determination. The aim of this study was
      to verify the sensitivity and specificity of Tg mRNA measurement, performed by
      quantitative real-time RT-PCR, in a series of 100 subjects (80 DTC patients and
      20 controls). From our data, the sensitivity and the specificity of the blood Tg
      mRNA measurement are 82.3 and 24.2%, respectively, with a positive predictive
      value and a negative predictive value of 65.6 and 43.7%, respectively. The
      comparison of the Tg mRNA with the serum Tg, measured by both chemiluminescent
      and ultrasensitive ELISA methods, confirmed the low specificity of the Tg mRNA
      assay. The hypothesis that Tg mRNA detectable levels could be predictive of
      future recurrences is not supported by the long follow-up (median, 7 yr; range, 3
      29 yr) of our disease-free patients, who did not develop any recurrences in their
      clinical history. Moreover, nine disease-free patients, who showed positive
      levels of Tg mRNA (11.8-336 pg equivalents/ micro g RNA), were confirmed to be
      serum Tg free, both in basal conditions and after recombinant human TSH
      stimulation, 4 yr after the Tg mRNA detection. In conclusion, we demonstrated
      that the Tg mRNA assay is of poor utility in the follow-up of DTC patients. On
      the contrary, serum Tg measurement is a very sensitive and specific thyroid tumor
      marker, and we recommend that the follow-up of patients affected by DTC must be
      performed using serum Tg rather than blood Tg mRNA measurement.

PMID- 14715825
TI  - Steroid 17alpha-hydroxylase deficiency--not rare everywhere.

PMID- 14715826
TI  - Two intronic mutations cause 17-hydroxylase deficiency by disrupting splice
      acceptor sites: direct demonstration of aberrant splicing and absent enzyme
      activity by expression of the entire CYP17 gene in HEK-293 cells.
AB  - To date, only two among 46 mutations in the CYP17 gene cause 17-hydroxylase
      deficiency (17OHD) by disrupting mRNA splice donor sites. We studied two subjects
      with intronic CYP17 mutations: a compound heterozygote for Y329D plus an AG to CG
      substitution at the 3' end of intron 2, and a homozygote for a TTTT deletion near
      the 3' end of intron 3. We hypothesized that both mutations caused 17OHD by
      disrupting splice acceptor sites. To prove this mechanism, the entire CYP17 genes
      (wild type and both mutations) were amplified, subcloned into pcDNA3, and
      expressed in HEK-293 cells. The mRNA derived from the wild-type CYP17 gene was
      correctly spliced and translated into active enzyme, as shown by the correct
      sequence in the RT-PCR products and by the 17-hydroxylation of progesterone. In
      contrast, cells expressing the mutant genes had no 17-hydroxylase activity. The
      mRNA derived from the AG to CG mutation used the first AG in exon 3 as the splice
      acceptor site, shifting the reading frame and introducing a stop codon. RNA
      derived from the TTTT deletion skipped exon 4 entirely, deleting 29 amino acids
      in-frame. Our data show that these are the first two 17OHD cases resulting from
      mutations that alter splice acceptor sites. These studies also demonstrate the
      feasibility of expressing the entire CYP17 gene, with simultaneous protein and
      RNA analysis, as a general methodology for characterizing how intronic CYP17
      mutations cause 17OHD.

PMID- 14715827
TI  - Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian
      patients with 17-hydroxylase deficiency.
AB  - We performed molecular genetic analysis of 24 subjects from 19 families with 17
      hydroxylase deficiency in Brazil. Of 7 novel CYP17 mutations, 2 (W406R and R362C)
      account for 50% and 32% of the mutant alleles, respectively. Both mutations were
      completely inactive when studied in COS-7 cells and yeast microsomes; however,
      phenotypic features varied among subjects. Some 46,XY individuals with these
      genotypes had ambiguous genitalia, and other subjects had normal blood pressure
      and/or serum potassium. We found mutations W406R and R362C principally in
      families with Spanish and Portuguese ancestry, respectively, suggesting that two
      independent founder effects contribute to the increased prevalence of 17
      hydroxylase deficiency in Brazil. Mutations Y329D and P428L retained a trace of
      activity, yet the two individuals with these mutations had severe hypertension
      and hypokalemia. The 46,XX female with mutation Y329D reached Tanner stage 5,
      whereas the 46,XY subject with mutation P428L remained sexually infantile. The
      severity of hypertension, hypokalemia, 17-deoxysteroid excess, and sex steroid
      deficiency varied, even among patients with completely inactive CYP17 protein(s).
      Spontaneous sexual development occurred only in 46,XX females with partial
      deficiencies. We conclude that other factors, in addition to CYP17 genotype,
      contribute to the phenotype of individual patients with 17-hydroxylase
      deficiency.

PMID- 14715828
TI  - Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene:
      effects of testosterone, alendronate, and estradiol treatment.
AB  - We present the fourth case of an adult man (29 yr old) affected by aromatase
      deficiency resulting from a novel homozygous inactivating mutation of the CYP19
      (P450(arom)) gene. At first observation, continuing linear growth, eunuchoid body
      proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The
      patient presented also a complex dysmetabolic syndrome characterized by insulin
      resistance, diabetes mellitus type 2, acanthosis nigricans, liver
      steatohepatitis, and signs of precocious atherogenesis. The analysis of the
      effects induced by the successive treatment with high doses of testosterone,
      alendronate, and estradiol allows further insight into the roles of androgens and
      estrogens on several metabolic functions. High doses of testosterone treatment
      resulted in a severe imbalance in the estradiol to testosterone ratio together
      with the occurrence of insulin resistance and diabetes mellitus type 2. Estrogen
      treatment resulted in an improvement of acanthosis nigricans, insulin resistance,
      and liver steatohepatitis, coupled with a better glycemic control and the
      disappearance of two carotid plaques. Furthermore, the study confirms previous
      data concerning the key role of estrogens on male bone maturation, at least in
      part, and regulation of gonadotropin secretion. The biopsy of the testis showed a
      pattern of total germ cell depletion that might be due to the concomitant
      presence of bilateral cryptorchidism. Thus, a possible role of estrogen in male
      reproductive function is suggested but without revealing a direct cause-effect
      relationship. Data from this case provide new insights into the role of estrogens
      in glucose, lipid, and liver metabolism in men. This new case of aromatase
      deficiency confirms previous data on bone maturation and mineralization, and it
      reveals a high risk for the precocious development of cardiovascular disease in
      young aromatase-deficient men.

PMID- 14715829
TI  - Increased prevalence of regurgitant valvular heart disease in acromegaly.
AB  - Cardiac involvement is common in acromegaly, but the prevalence of valvular
      abnormalities in patients with acromegaly has not been documented and is the
      topic of this study. In a prospective study design, 40 consecutive patients with
      acromegaly and 120 control subjects (matched for age, sex, hypertension, and left
      ventricular systolic function) were studied. All patients and controls were
      evaluated using conventional two-dimensional and Doppler echocardiography.
      Significant valve disease was more prevalent in acromegalics compared with
      controls (22% vs. 6.7%, respectively; P = 0.005). Aortic valve regurgitation
      (>/=>trace severity) was present in 30% of patients vs. 7% of controls (P <
      0.001), and mitral regurgitation (>/=moderate severity) was absent in controls
      but present in 5% of acromegalics (P = 0.014 vs. controls). Binary logistic
      regression analysis showed a significant impact only for disease duration on
      valvular disease, with an odds ratio of 1.19 (95% confidence interval, 1.028
      1.376; P = 0.019). Acromegaly is associated with an increased prevalence of
      regurgitant valvular heart disease. This is dependent on the duration of exposure
      to increased GH concentrations, with a 19% increase in odds per year. This
      increased prevalence of occult valvular disease indicates that these patients
      require appropriate follow-up care and monitoring, especially patients with
      inadequate control of GH overproduction.

PMID- 14715830
TI  - Vitamin D status as a determinant of peak bone mass in young Finnish men.
AB  - Severe vitamin D deficiency causes rickets, but scarce data are available about
      the extent to which vitamin D status determines the development of the peak bone
      mass in young adults. Our aim was to evaluate the prevalence of vitamin D
      deficiency [serum 25-hydroxyvitamin D (25-OHD) less than the lower limit of the
      reference range of 20-105 nmol/liter] and the relationship between vitamin D
      status and peak bone mass among young Finnish men. A cross-sectional study of
      determinants of peak bone mass with data on lifestyle factors collected
      retrospectively was performed in 220 young men, aged 18.3-20.6 yr. One hundred
      and seventy men were recruits of the Finnish Army, and 50 were men of similar age
      who had postponed their military service for reasons not related to health. Bone
      mineral content, bone mineral density, and scan area were measured in lumbar
      spine and upper femur by dual energy x-ray absorptiometry. Serum 25-OHD
      concentrations were followed prospectively for 1 yr. In July 2000, only 0.9% of
      the men had vitamin D deficiency, but 6 months later, in the winter, the
      respective percentage was 38.9%. After adjusting for age, height, weight,
      exercise, smoking, calcium, and alcohol intake, there existed a positive
      correlation between serum 25-OHD and bone mineral content at lumbar spine (P =
      0.057), femoral neck (P = 0.041), trochanter (P = 0.010), and total hip (P =
      0.025). The correlation coefficients for the bone mineral densities at the four
      measurement sites were 0.035, 0.061, 0.056, and 0.068, respectively. No
      correlation was found to scan area. We conclude that vitamin D deficiency is very
      common in Finnish young men in the winter, and it may have detrimental effects on
      the acquisition of maximal peak bone mass. As in Finland vitamin D
      supplementation to infants is now stopped at the age of 3 yr, it can be asked
      whether at our latitude it should be continued from that age onward, not for the
      prevention of rickets, but as prophylaxis for osteoporosis.

PMID- 14715831
TI  - Features of the metabolic syndrome after childhood craniopharyngioma.
AB  - Obesity and multiple pituitary hormone deficiency are common complications after
      surgery for childhood craniopharyngioma. We hypothesized that post
      craniopharyngioma surgery, children are at high risk for the metabolic syndrome,
      including insulin resistance due to excess weight gain and GH deficiency. This
      study characterized body composition (anthropometry and dual energy x-ray
      absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females;
      age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In
      9 subjects, outcomes were compared with those of healthy age-, sex-, body mass
      index-, and pubertal stage-matched controls. Insulin sensitivity was measured by
      40-min iv glucose tolerance test. Seventy-three percent of subjects were
      overweight or obese. Sixty-six percent had normal growth velocity without GH
      treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with
      controls. However, there was no significant difference in total body fat.
      Subjects had higher fasting triglycerides (P = 0.02) and lower high density
      lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin
      sensitivity was equally reduced for subjects and controls (P = 0.86). After
      craniopharyngioma removal, patients had more features of the metabolic syndrome
      compared with controls. This could be a result of hypothalamic damage causing
      obesity and GH deficiency. Further studies exploring predictors of the metabolic
      syndrome after craniopharyngioma surgery are required.

PMID- 14715832
TI  - Adiponectin, an adipocyte-derived protein, predicts future insulin resistance:
      two-year follow-up study in Japanese population.
AB  - It has been reported that the serum adiponectin level was negatively correlated
      with body mass index (BMI), insulin resistance index, and triglycerides and was
      positively correlated with high-density lipoprotein cholesterol in several cross
      sectional studies. However, the causal relationship has not been elucidated. We
      investigated whether the baseline adiponectin level could predict subsequent
      changes in insulin resistance, lipid profile, or body weight in a 2-yr
      longitudinal study. This study included 590 male Japanese subjects, aged 30-65
      yr, who received annual health checkups in both 2000 and 2002. Blood pressure,
      heart rate, and anthropometric and metabolic parameters, including serum insulin
      and adiponectin levels, were determined. The insulin resistance index was
      calculated based on homeostasis model assessment. Baseline adiponectin level was
      not correlated with the subsequent change in lipid profile or BMI in 2 yr after
      adjustment for each baseline value. However, the baseline adiponectin level was
      negatively correlated with subsequent changes in insulin and insulin resistance
      index based on homeostasis model assessment, even after adjustment for change in
      BMI (r = -0.162 and r = -0.140, respectively). These findings suggest that the
      serum adiponectin concentration predicts subsequent changes in insulin
      resistance, but not in lipid profile or body weight.

PMID- 14715833
TI  - Recombinant human thyrotropin stimulation of fluoro-D-glucose positron emission
      tomography uptake in well-differentiated thyroid carcinoma.
AB  - TSH stimulates thyrocyte metabolism, glucose transport, and glycolysis. 2-Deoxy-2
      [18F]fluoro-D-glucose (FDG) is a glucose analog used in positron emission
      tomography (PET) to detect occult well-differentiated thyroid carcinoma. The
      objective of this study was to examine the effects of recombinant human TSH
      (rTSH) on FDG PET uptake in patients with residual or recurrent disease. Seven
      patients with well-differentiated thyroid carcinoma, negative 131-I scintigraphy,
      and biochemical evidence of residual disease were randomized and prospectively
      studied with FDG PET both on thyroid hormone suppression and rTSH stimulation
      within 1 wk. All lesions seen on the TSH suppression scans were seen on the rTSH
      stimulation studies. rTSH stimulation studies identified four additional lesions
      not seen on TSH suppression. One patient was positive on rTSH stimulation alone.
      The mean (2.54 +/- 0.72 vs. 1.79 +/- 0.88) and maximum (2.49 +/- 0.95 vs. 1.74 +/
      0.81) lesion to background ratios were significantly higher with rTSH
      stimulation, compared with TSH suppression (P = 0.02 for both). rTSH stimulation
      improves the detectability of occult thyroid metastases with FDG PET, compared
      with scans performed on TSH suppression.

PMID- 14715834
TI  - Familial isolated hyperparathyroidism is rarely caused by germline mutation in
      HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome.
AB  - Familial isolated hyperparathyroidism (FIHP) can result occasionally from the
      incomplete expression of a syndromic form of familial hyperparathyroidism (HPT),
      specifically multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric
      hypercalcemia, or the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The cause
      of FIHP has not been identified in the majority of families. We investigated 32
      families with FIHP to determine the frequency of occult mutation in HRPT2, the
      gene causing HPT-JT. All families had negative clinical testing for MEN1,
      hypocalciuric hypercalcemia, and HPT-JT and negative mutational screening of MEN1
      and CASR, the gene for the calcium-sensing receptor. Thus, an extended effort was
      made to exclude each of the principal syndromic causes of FIHP. The families were
      characterized by young probands (42 +/- 3 yr) and occasionally unusual
      parathyroid histology, including four families with one case of parathyroid
      cancer. We had speculated that there was a high frequency of occult mutation in
      HRPT2 among such carefully screened kindreds. This hypothesis became testable
      with the recent identification of that gene. Among the 32 FIHP families, only a
      single one was found to have a mutation in HRPT2 (679insAG); this mutation
      predicts premature truncation of its gene product, parafibromin, and thus its
      presumed inactivation. Even accounting for families with one of the three occult
      syndromes and false negative biochemical or DNA testing, these results indicate
      that an unexpectedly large fraction of FIHP has currently unrecognized causes.

PMID- 14715835
TI  - Determinants of growth during gonadotropin-releasing hormone analog therapy for
      precocious puberty.
AB  - In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa)
      often decreases height velocity below normal. Based on previous animal studies,
      we hypothesized that this impaired growth is due to excessive advancement in
      growth plate senescence induced by the prior estrogen exposure. This hypothesis
      predicts that the height velocity during treatment will be inversely related to
      the severity of prior estrogen exposure. We analyzed data from 100 girls (age,
      5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During
      GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/-
      SD). The absolute height velocity correlated most strongly with the bone age
      (BA), which we used as a surrogate marker for growth plate senescence (r = 
      0.727, P < 0.001). The severity of the growth abnormality (height velocity SD
      score for age) correlated inversely with markers of the severity of prior
      estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner
      breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01).
      Stepwise regression confirmed that BA was the best independent predictor of
      growth during GnRHa therapy. The findings are consistent with our hypothesis that
      impaired growth during GnRHa therapy is due, at least in part, to premature
      growth plate senescence induced by the prior estrogen exposure.

PMID- 14715836
TI  - The metabolic syndrome in overweight Hispanic youth and the role of insulin
      sensitivity.
AB  - The prevalence of the metabolic syndrome is highest among Hispanic adults.
      However, studies exploring the metabolic syndrome in overweight Hispanic youth
      are lacking. Subjects were 126 overweight children (8-13 yr of age) with a family
      history for type 2 diabetes. The metabolic syndrome was defined as having at
      least three of the following: abdominal obesity, low high-density lipoprotein
      (HDL) cholesterol, hypertriglyceridemia, hypertension, and/or impaired glucose
      tolerance. Insulin sensitivity was determined by the frequently sampled iv
      glucose tolerance test and minimal modeling. The prevalence of abdominal obesity,
      low HDL cholesterol, hypertriglyceridemia, systolic and diastolic hypertension,
      and impaired glucose tolerance was 62, 67, 26, 22, 4, and 27%, respectively. The
      presence of zero, one, two, or three or more features of the metabolic syndrome
      was 9, 22, 38, and 30%, respectively. After controlling for body composition,
      insulin sensitivity was positively related to HDL cholesterol (P < 0.01) and
      negatively related to triglycerides (P < 0.001) and systolic (P < 0.01) and
      diastolic blood pressure (P < 0.05). Insulin sensitivity significantly decreased
      (P < 0.001) as the number of features of the metabolic syndrome increased. In
      conclusion, overweight Hispanic youth with a family history for type 2 diabetes
      are at increased risk for cardiovascular disease and type 2 diabetes, and this
      appears to be due to decreased insulin sensitivity. Improving insulin resistance
      may be crucial for the prevention of chronic disease in this at-risk population.

PMID- 14715837
TI  - The prospective association of serum insulin-like growth factor I (IGF-I) and IGF
      binding protein-1 levels with all cause and cardiovascular disease mortality in
      older adults: the Rancho Bernardo Study.
AB  - The IGF system has been implicated in cardiovascular disease (CVD) development.
      The prospective association of serum IGF-I and IGF-binding protein-1 (IGFBP-1)
      with all cause, ischemic heart disease (IHD), and non-IHD CVD mortality was
      examined in 633 men and 552 nonestrogen-using postmenopausal women, aged 51-98 yr
      (mean, 74 yr) in 1988-1992, who were followed through July 2001 (96% follow-up).
      During the 9- to 13-yr follow-up, there were 522 deaths; 224 were attributed to
      CVD, and 105 were caused by IHD. IGF-I and IGFBP-1 were independently and jointly
      related to risk of IHD mortality. In a proportional hazards model including both
      IGF-I and IGFBP-1 and adjusting for CVD risk factors, the relative risk of IHD
      mortality was 38% higher for every 40 ng/ml (1 SD) decrease in IGF-I (95%
      confidence interval, 1.09-1.76; P = 0.005) and 3.11 times greater for those in
      the lowest quintile of IGFBP-1 (95% confidence interval, 1.74-5.56; P < 0.001)
      compared with those with higher IGFBP-1 levels. IGF-I and IGFBP-1 (alone or in
      combination) were not related to risk of all cause or non-IHD CVD mortality. We
      conclude that low baseline levels of IGF-I and IGFBP-1 increase the risk of fatal
      IHD among elderly men and women independent of prevalent IHD and CVD risk
      factors.

PMID- 14715838
TI  - Estradiol supplementation in postmenopausal women doubles rebound-like release of
      growth hormone (GH) triggered by sequential infusion and withdrawal of
      somatostatin: evidence that estrogen facilitates endogenous GH-releasing hormone
      drive.
AB  - We postulated that short-term estradiol replacement in postmenopausal women may
      act, in part, by facilitating endogenous GHRH release or action. A prediction of
      this hypothesis is that estradiol repletion should enhance postsomatostatin
      rebound GH secretion, which appears to be driven by hypothalamic outflow of GHRH.
      To this end, we administered placebo and estradiol to eight healthy estrogen
      withdrawn postmenopausal volunteers in a prospectively randomized, patient
      blinded, within-subject crossover design for a total of 36 d. Rebound release of
      GH was assessed between d 7 and 36 of intervention on separate randomly ordered
      mornings after continuous iv infusion of saline or somatostatin (9 micro g/kg.h
      for 3 h). Secretion was quantitated by frequent (10-min) blood sampling for 7 h,
      GH chemiluminescence assay, and deconvolution analysis. Compared with placebo,
      estradiol replacement: 1) stimulated spontaneous pulsatile GH secretion by 3.5
      fold (95% confidence interval, 2.1- to 5.6-fold) (P < 0.001); and 2) amplified
      the mass of GH secreted in response to abrupt somatostatin withdrawal by 2.1-fold
      (95% confidence interval, 1.3- to 3.4-fold) (P = 0.003). Estrogenic augmentation
      of rebound-like GH secretion was specific, because the pharmacological effects of
      exogenous GHRH (1 micro g/kg) and GH-releasing peptide-2 (1 micro g/kg, a
      synthetic ghrelin analog) were not affected. In summary, short-term
      supplementation with estradiol in postmenopausal individuals doubles the mass of
      rebound-like GH secretion induced by abrupt somatostatin withdrawal without
      modifying stimulation by a pharmacological dose of GHRH or GH-releasing peptide
      2. Accordingly, we hypothesize that estradiol stimulates pulsatile GH secretion,
      at least in part, by enhancing the release and/or action of hypothalamic GHRH.

PMID- 14715839
TI  - Melatonin in patients with reduced REM sleep duration: two randomized controlled
      trials.
AB  - Recent data suggest that melatonin may influence human physiology, including the
      sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid
      eye-movement (REM) sleep expression is strongly circadian modulated, and the
      impact of REM sleep on primary brain functions, metabolic processes, and immune
      system function has become increasingly clear over the past decade. In our study,
      we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans.
      Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with
      unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25%
      or more below age norm according to diagnostic polysomnography) were included in
      two consecutive, randomized, double-blind, placebo-controlled, parallel design
      clinical trials. Patients received 3 mg melatonin daily, administered between
      2200 and 2300 h for 4 wk. The results of the study show that melatonin was
      significantly more effective than placebo: patients on melatonin experienced
      significant increases in REM sleep percentage (baseline/melatonin, 14.7/17.8 vs.
      baseline/placebo, 14.3/12.0) and improvements in subjective measures of daytime
      dysfunction as well as clinical global impression score. Melatonin did not shift
      circadian phase or suppress temperature but did increase REM sleep continuity and
      promote decline in rectal temperature during sleep. These results were confirmed
      in patients who received melatonin in the second study (REM sleep percentage
      baseline/placebo/melatonin, 14.3/12.0/17.9). In patients who received melatonin
      in the first study and placebo in the second, the above mentioned effects
      outlasted the period of melatonin administration and diminished only slowly over
      time (REM sleep percentage baseline/melatonin/placebo, 14.7/17.8/16.2). Our
      findings show that exogenous melatonin, when administered at the appropriate
      time, seems to normalize circadian variation in human physiology. It may,
      therefore, have a strong impact on general health, especially in the elderly and
      in shift workers.

PMID- 14715840
TI  - Comparison of the insulin action parameters from hyperinsulinemic clamps with
      homeostasis model assessment and QUICKI indexes in subjects with different
      endocrine disorders.
AB  - The aim of this study was to compare insulin sensitivity expressed by the
      hyperinsulinemic clamp and by the homeostasis model assessment (HOMA) and QUICKI
      indexes in subjects with various disorders influencing insulin action. We
      examined 41 type 2 diabetic patients, 20 insulinoma patients, 32 women with
      polycystic ovary syndrome, 16 patients with primary hyperaldosteronism, 12
      patients with essential high renin hypertension, and 47 healthy subjects. The
      metabolic clearance rate of glucose and the insulin sensitivity index calculated
      from the clamps were compared with both the HOMA and QUICKI indexes. The
      relationship of insulin action to body mass index, serum cholesterol, and
      triglycerides as well as to systolic and diastolic blood pressures was also
      evaluated. Body mass index was very strongly associated with the insulin
      sensitivity index (r = -0.70; P < 0.0001) in the entire cohort of 168 subjects.
      Cholesterol, triglycerides, and blood pressure influenced insulin action in the
      healthy subjects and type 2 diabetic patients. A significant relationship was
      observed between the insulin sensitivity index and the HOMA or QUICKI indexes in
      healthy subjects (r = -0.66; P < 0.0001), type 2 diabetic patients (r = -0.68; P
      < 0.0001), and women with polycystic ovary syndrome (r = -0.65; P < 0.0001). We
      did not find any relationship between the above variables in the patients with
      insulinoma or primary hyperaldosteronism. The HOMA and QUICKI indexes do not
      offer the same information as glucose clamps in the rare cases with differently
      impaired peripheral or hepatic insulin action.

PMID- 14715841
TI  - Relationship between serum gonadotropins and spermatogenic suppression in men
      undergoing steroidal contraceptive treatment.
AB  - This study aimed to establish whether the degree of suppression of serum FSH and
      LH was related to sperm concentration in three testosterone (T) plus progestin
      contraceptive regimens. We measured serum FSH and LH using a modified, highly
      sensitive immunofluorometric assay in samples obtained from three published
      studies using T enanthate (TE; 100 and 200 mg weekly) plus daily oral doses of
      cyproterone acetate (CPA; 5-100 mg), levonogestrel (LNG; 150-500 micro g), or
      desogestrel (DSG; 150-300 micro g). Overall, men with sperm concentrations below
      0.1 million/ml had significantly lower gonadotropin levels (serum FSH,
      approximately 0.12 IU/liter; serum LH, approximately 0.05 IU/liter) than
      oligospermic men (sperm concentrations, 0.1-5 million/ml; serum FSH, 0.23-0.5
      IU/liter; serum LH, 0.05-0.56 IU/liter), but the relationship was weak,
      indicating the possible existence of other determinants. Multivariate logistic
      regression was used to identify the influence of candidate predictors of
      spermatogenic effects of the T plus progestin regimens. In the LNG and DSG
      studies, the marked suppression of serum LH to less than 5% of baseline values
      (<0.15 IU/liter) was a consistent and highly significant predictor of sperm
      concentration (reduced to 2-7% that seen at higher LH levels) and the likelihood
      of its suppression below 1 million/ml (a proposed threshold for contraceptive
      efficacy). Serum FSH was not a significant independent predictor. The use of DSG
      and CPA (but not LNG) was a significant independent predictor of sperm
      suppression, and regimens that contained 200 mg TE weekly caused less
      spermatogenic suppression than 100 mg TE weekly. These findings suggest that T
      progestin contraceptive regimens suppress sperm concentration by gonadotropin
      dependent and -independent mechanisms. The suppression of serum LH is a major
      predictor of the suppression of sperm concentration suppression in the LNG and
      DSG treatment studies. On the other hand, the greater spermatogenic suppression
      in regimens containing DSG or CPA suggests that these progestins have additional
      actions to suppress spermatogenesis via a gonadotropin-independent mechanism(s)

PMID- 14715842
TI  - Plasma resistin concentrations measured by enzyme-linked immunosorbent assay
      using a newly developed monoclonal antibody are elevated in individuals with type
      2 diabetes mellitus.
AB  - Resistin is an adipocyte-derived peptide that might play a role in obesity and
      insulin resistance. However, its role in humans is largely unclear. Although many
      studies have measured the expression of human resistin in tissues, the
      circulating concentrations of resistin and its relation to metabolic parameters
      in humans are unknown. We developed an ELISA for human resistin and measured
      plasma concentrations in aged individuals with or without type 2 diabetes
      mellitus. To validate the results of plasma resistin concentrations in our
      subjects, plasma adiponectin concentrations were also determined, which were
      higher in nondiabetic subjects than in type 2 diabetic patients and correlated
      with the homeostasis model assessment for insulin resistance (HOMA-IR). Log
      transformed plasma resistin concentrations (log-resistin) were higher in diabetic
      patients compared with normal individuals (0.50 +/- 0.39 vs. 0.28 +/- 0.51 ng/ml;
      P < 0.001), and this difference was significant after controlling for gender and
      body mass index. Log-resistin did not show a significant correlation with HOMA
      IR, waist circumference, body mass index, blood pressure, or total cholesterol.
      The plasma glucose concentration was an independent factor associated with log
      resistin. In conclusion, plasma resistin concentrations are elevated in patients
      with type 2 diabetes, but are not associated with insulin resistance or obesity.

PMID- 14715843
TI  - Ghrelin receptor gene: identification of several sequence variants in extremely
      obese children and adolescents, healthy normal-weight and underweight students,
      and children with short normal stature.
AB  - GH secretagogue receptor (GHSR, ghrelin receptor) is involved in regulation of
      body weight and GH secretion. We initially analyzed two single-nucleotide
      polymorphisms of the GHSR in up to 184 extremely obese children and adolescents
      and up to 184 healthy underweight students. The frequency of the 171T allele of
      rs495225 was higher in our obese samples (75.0%) than in the underweight
      individuals (70.2%; nominal P = 0.14). This trend could not be substantiated in
      an additional association study in 270 obese and 145 underweight and normal
      weight individuals and in a transmission disequilibrium test based on 387 obesity
      trios (transmission rate of 171T, 51.8%; nominal P = 0.53). Additionally, the
      coding region of GHSR was systematically screened, and seven sequence variants
      were identified in 93 obese, 96 normal weight, and 94 underweight individuals and
      43 children with short normal stature (SNS). Five silent single-nucleotide
      polymorphisms showed similar genotype frequencies in the different weight groups
      and SNS children (all nominal P > 0.3). Two novel missense variants were detected
      only in one obese carrier and one SNS child, respectively. In conclusion, we did
      not obtain conclusive evidence for an involvement of the ghrelin receptor gene in
      body weight regulation or SNS in our study groups.

PMID- 14715844
TI  - Impact of routine measurement of serum calcitonin on the diagnosis and outcome of
      medullary thyroid cancer: experience in 10,864 patients with nodular thyroid
      disorders.
AB  - The survival rate of patients with medullary thyroid carcinoma (MTC) is
      significantly better in patients diagnosed and treated when the tumor is limited
      to the thyroid. In a pioneer study carried out in 1991, we demonstrated that
      routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed
      the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than
      routine fine needle aspiration cytology (FNAC). This finding has been confirmed
      in subsequent studies. In the present study we report the results of CT screening
      in 10,864 patients with thyroid nodular disease seen in the years 1991-1998
      (group 1). We analyzed the prevalence of MTC and compared their outcomes with
      those of a historical group of patients (group 2) diagnosed before the
      introduction of CT screening (1970-1990). The prevalence of MTC found by CT
      screening in group 1 was 0.40% (44 patients). A positive CT test had a higher
      diagnostic sensitivity and specificity compared with FNAC. CT screening allowed
      the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004).
      Normalization of serum CT levels (undetectable) after surgery was more frequently
      observed in group 1. At the end of follow-up, complete remission was observed in
      59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC
      is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250
      patients). In addition, screening thyroid nodules with serum CT measurement
      allows the diagnosis and treatment of MTC at an earlier stage, resulting in a
      better outcome compared with MTC not detected by serum CT measurement. One of the
      reasons for this finding is that increasing the preoperative diagnostic accuracy
      of MTC prompts the surgeon to perform a more radical and possibly curative
      treatment. On this basis, routine measurement of basal serum CT levels should be
      considered an integral part of the diagnostic evaluation of thyroid nodules.

PMID- 14715845
TI  - Cytotoxic T lymphocyte-associated molecule-4 polymorphism and relapse of Graves'
      hyperthyroidism after antithyroid withdrawal.
AB  - We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1
      of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves'
      disease (GD) patients and 171 controls. Our primary aim was to test for the
      association of this SNP with the relapse of the hyperthyroidism after antithyroid
      withdrawal. Our secondary aim was to investigate the relationship between GD
      patients and controls according to the SNP genotypes. All GD patients were
      divided into the following three groups according to the time of relapse after
      drug discontinuation: group 1, early relapse within 9 months; group 2, relapse
      between 10 and 36 months; and group 3, relapse 3 or more years after
      discontinuation of treatment. There was a significant difference of genotype
      frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups
      of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39%
      in groups 1, 2, and 3, respectively. Compared with controls, a strong association
      (P < 0.001) of G allele was found for group 1, and moderate significance (P =
      0.04) was found for group 2, but no association (P = 0.33) was found for group 3.
      At the end of treatment, the percentage of patients with persistent TSH-receptor
      antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P =
      0.004). Using 3 yr as the cutoff point for multivariate logistic regression
      analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with
      A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of
      treatment, and positive TSH-receptor antibody at the end of treatment were
      independent risk factors of recurrence. We conclude that the A/G polymorphism of
      the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD.
      The G/G genotype is associated with poor outcome.

PMID- 14715846
TI  - Growth hormone secretion and leptin in morbid obesity before and after
      biliopancreatic diversion: relationships with insulin and body composition.
AB  - Obesity is characterized by increased leptin levels and insulin resistance,
      whereas blunted GH secretion is paired with normal, low, or high plasma IGF-I
      levels. To investigate body composition in human obesity and the interactions
      among the GH-IGF-I axis, leptin, and insulin resistance [measured with the
      homeostasis model assessment (HOMA) score], we studied 15 obese females, aged 23
      54 yr (mean age, 42.7 +/- 2.6), with a body mass index (BMI) of 44.02 +/- 1.45
      kg/m(2), who underwent treatment by biliopancreatic diversion (BPD), before and
      after surgery (16-24 months; BMI, 28.29 +/- 0.89 kg/m(2)). Our controls were 15
      normal females, aged 28-54 yr (mean age, 40.8 +/- 2.3 yr), with a BMI of 27.52 +/
      0.53 kg/m(2). Insulin and leptin levels and HOMA scores were higher pre-BPD than
      in the controls. The GH response to GHRH was blunted, with a GH peak and GH area
      under the curve (AUC) significantly lower than those in controls. IGF-I and IGF
      binding protein-3 (IGFBP-3) were also lower than control values. After surgery,
      BMI, fat mass, lean body mass, HOMA, insulin, and leptin significantly decreased.
      Furthermore, the GH response to GHRH severely increased; IGF-I and IGFBP-3 levels
      did not significantly vary. Considering all subjects, correlation analysis showed
      a strong positive correlation between insulin and leptin, and a negative
      correlation between insulin and GH peak and between insulin and GH AUC.
      Regression analysis performed grouping pre- and post-BPD indicated that leptin
      and GH peak or AUC could best be predicted from insulin levels. The surgical
      treatment of severe obesity after stabilization of body weight decreases BMI and
      fat mass while preserving normal lean body mass as well as positively influencing
      insulin sensitivity and thus aiding the normalization of leptin levels. The
      insulin reduction may be mainly involved in the increase in the GH response to
      GHRH through various possible central and peripheral mechanisms while decreasing
      the peripheral sensitivity to GH itself, as shown by the stable nature of the IGF
      I and IGFBP-3 values. Our findings suggest that the changes in insulin levels are
      the starting point for changes in both leptin levels and the somatotrope axis
      after BPD.

PMID- 14715847
TI  - Iodine nutrition in breast-fed infants is impaired by maternal smoking.
AB  - Lack of iodine for thyroid hormone formation during the fetal stage and/or the
      first years of life may lead to developmental brain damage. During the period of
      breastfeeding, thyroid function of the infant depends on iodine in maternal milk.
      We studied healthy, pregnant women admitted for delivery and their newborn
      infants. Cotinine in urine and serum was used to classify mothers as smokers (n =
      50) or nonsmokers (n = 90). Smoking and nonsmoking mothers had identical urinary
      iodine on d 5 after delivery, but smoking was associated with reduced iodine
      content in breast milk (smokers 26.0 micro g/liter vs. nonsmokers 53.8 micro
      g/liter; geometric mean, P < 0.001) and in the infants' urine (smokers 33.3 micro
      g/liter, vs. nonsmokers 50.4 micro g/liter, P = 0.005). Results were consistent
      in multivariate linear models and by logistic regression analysis. The odds ratio
      for smoking vs. nonsmoking mothers to have lower breast milk than urinary iodine
      content was 8.4 (95% confidence interval, 3.5-20.1). In smokers, iodine transfer
      into breast milk correlated negatively to urinary cotinine concentration. Smoking
      mothers had significantly higher serum levels of thiocyanate, which may
      competitively inhibit the sodium-iodide symporter responsible for iodide
      transport in the lactating mammary gland. Smoking during the period of
      breastfeeding increases the risk of iodine deficiency-induced brain damage in the
      child. Women who breastfeed should not smoke, but if they do, an extra iodine
      supplement should be considered.

PMID- 14715848
TI  - Effects of the phytoestrogen genistein on the circulating soluble receptor
      activator of nuclear factor kappaB ligand-osteoprotegerin system in early
      postmenopausal women.
AB  - We investigated the serum levels of both receptor activator of nuclear factor
      kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in
      postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54
      mg/d), hormone replacement therapy (n = 30; 1 mg/d 17beta-estradiol combined with
      norethisterone acetate) and placebo (n = 30). By comparison with placebo, the
      soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 +/- 7%; P
      < 0.01 vs. placebo 81 +/- 24%) and in hormone replacement therapy-treated women (
      11 +/- 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was
      found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in
      urinary deoxypyridinoline, a bone resorption marker. A negative correlation was
      observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in
      femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that
      the sRANKL-OPG system may mediate the beneficial effects of genistein on bone
      remodeling in postmenopausal women.

PMID- 14715849
TI  - Importance of estrogen on bone health in Turner syndrome: a cross-sectional and
      longitudinal study using dual-energy X-ray absorptiometry.
AB  - Osteoporosis and fractures are features in adults with Turner syndrome (TS).
      Using dual-energy x-ray absorptiometry, correcting bone mineral content (BMC) for
      height and lean mass (LTM) avoids misclassification of short children as
      osteopenic. Total body (TB), lumbar spine (LS), and femoral neck (FN) dual-energy
      x-ray absorptiometry scans were performed on 83 patients with TS (aged 4-24 yr).
      A prepubertal subgroup (n = 17) receiving GH was followed for 24 months. Age z
      scores for height, TB BMC, LTM, the BMC/LTM ratio, and LS volumetric bone mineral
      density (vBMD) decreased significantly (P < 0.001) with age in prepubertal
      subjects (n = 51) but were constant in the combined pubertal and postmenarchal
      group (n = 32). Osteopenia was found in 14.5% (TB), 15.8% (LS), and 28.4% (FN) of
      patients. In the longitudinal subgroup, TB BMC z-scores decreased by -0.28 (0.31)
      in subjects remaining prepubertal (n = 11) but increased by 0.71 (0.56) in
      subjects entering puberty (n = 6; P = 0.007). The z-scores for height and LTM
      increased in both groups. Our results show a height-independent prepubertal
      decrease in bone mass accrual, which ceased with puberty. Optimizing bone mass in
      TS may require earlier induction of puberty than currently recommended. However,
      reduced FN volumetric bone mineral density and a dissociation of bone and muscle
      measures were age independent, suggesting an additional intrinsic bone defect.

PMID- 14715850
TI  - Decreased plasma adiponectin concentrations are closely related to hepatic fat
      content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic
      patients.
AB  - The effect of pioglitazone (PIO) on plasma adiponectin concentration, endogenous
      glucose production (EGP), and hepatic fat content (HFC) was studied in 11 type 2
      diabetic patients (age, 52 +/- 2 yr; body mass index, 29.6 +/- 1.1 kg/m(2);
      HbA(1c), 7.8 +/- 0.4%). HFC (magnetic resonance spectroscopy) and basal plasma
      adiponectin concentration were quantitated before and after PIO (45 mg/d) for 16
      wk. Subjects received a 3-h euglycemic insulin (100 mU/m(2).min) clamp combined
      with 3-[(3)H] glucose infusion to determine rates of EGP and tissue glucose
      disappearance (Rd) before and after PIO. PIO reduced fasting plasma glucose (10.0
      +/- 0.7 to 7.2 +/- 0.6 mmol/liter, P < 0.01) and HbA(1c) (7.8 +/- 0.4 to 6.5 +/-
      0.3%, P < 0.01) despite increased body weight (83.0 +/- 3.0 to 86.4 +/- 3.0 kg, P
      < 0.01). PIO improved Rd (6.6 +/- 0.6 vs. 5.2 +/- 0.5 mg/kg.min, P < 0.005) and
      reduced EGP (0.23 +/- 0.04 to 0.05 +/- 0.02 mg/kg.min, P < 0.01) during the 3-h
      insulin clamp. After PIO treatment, HFC decreased from 21.3 +/- 4.2 to 11.0 +/-
      2.4% (P < 0.01), and plasma adiponectin increased from 7 +/- 1 to 21 +/- 2 micro
      g/ml (P < 0.0001). Plasma adiponectin concentration correlated negatively with
      HFC (r = -0.60, P < 0.05) and EGP (r = -0.80, P < 0.004) and positively with Rd
      before (r = 0.68, P < 0.02) pioglitazone treatment; similar correlations were
      observed between plasma adiponectin levels and HFC (r = -0.65, P < 0.03) and Rd
      after (r = 0.70, P = 0.01) pioglitazone treatment. EGP was almost completely
      suppressed after pioglitazone treatment; taken collectively, plasma adiponectin
      concentration, before and after pioglitazone treatment, still correlated
      negatively with EGP during the insulin clamp (r = -0.65, P < 0.001). In
      conclusion, PIO treatment in type 2 diabetes causes a 3-fold increase in plasma
      adiponectin concentration. The increase in plasma adiponectin is strongly
      associated with a decrease in hepatic fat content and improvements in hepatic and
      peripheral insulin sensitivity. The increase in plasma adiponectin concentration
      after thiazolidinedione therapy may play an important role in reversing the
      abnormality in hepatic fat mobilization and the hepatic/muscle insulin resistance
      in patients with type 2 diabetes.

PMID- 14715851
TI  - Impaired glucose tolerance and reduced beta-cell function in overweight Latino
      children with a positive family history for type 2 diabetes.
AB  - The objective of this study was to examine relationships between impaired glucose
      tolerance (IGT) and body composition and insulin-related phenotypes in 150
      overweight Latino children with a family history of type 2 diabetes. Glucose
      tolerance was assessed by an oral glucose challenge. Body composition was
      assessed by dual energy x-ray absorptiometry and magnetic resonance imaging.
      Insulin sensitivity, the acute insulin response, and the disposition index (DI),
      as an index of beta-cell function, were determined by an iv glucose tolerance
      test and compared between normal glucose-tolerant and IGT children. IGT was
      present in 28% of children, and was similar across obesity groups, but higher in
      children exposed to gestational diabetes mellitus (41% IGT). There were no
      significant differences in body composition, fat distribution, insulin
      sensitivity, or acute insulin response, but DI was significantly lower in IGT
      children by 16% (P < 0.02), and DI was inversely related to age. In conclusion,
      IGT is present in 28% of overweight Latino children with a family history of type
      2 diabetes, is not influenced by obesity, is more prevalent in children exposed
      to gestational diabetes mellitus, and is related to poor beta-cell function,
      which shows signs of deterioration with age in this population.

PMID- 14715852
TI  - Do height-related variations in insulin-like growth factors underlie the
      associations of stature with adult chronic disease?
AB  - Tall people, particularly those with long legs, have an increased risk of
      developing cancer but a reduced risk of cardiovascular disease and type II
      diabetes. We examined associations of stature and body mass index with IGF-I, IGF
      II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50-70 yr to
      investigate whether variations in growth factor levels underlie associations of
      anthropometry with a number of adult diseases. Height and leg and trunk length
      were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP
      3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk
      length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and
      inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per
      milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7,
      and 578.8 (P(trend) = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5
      (P(trend) < 0.01), suggesting that variations in IGFBP-2, or a factor influencing
      its levels in the circulation, may contribute to biological mechanisms underlying
      height-disease associations. We conclude that whereas growth-influencing
      exposures during childhood, which may operate through effects on IGF-I levels,
      have long-term influences on disease risk, they do not necessarily program IGF-I
      levels throughout life. The associations of anthropometry with IGFBP-2 merit
      additional investigation.

PMID- 14715853
TI  - Contribution of circulating lipids to the improved outcome of critical illness by
      glycemic control with intensive insulin therapy.
AB  - Compared with the conventional approach, which recommended only insulin therapy
      when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood
      glucose levels less than 6.1 mmol/liter with intensive insulin therapy has shown
      to reduce intensive care mortality, acute renal failure, critical illness
      polyneuropathy, and bloodstream infections in critically ill patients by about
      40%. This study of 363 patients, requiring intensive care for more than 7 d and
      randomly assigned to either conventional or intensive insulin therapy, examines
      the effects of intensive insulin therapy on glucose and lipid homeostasis and
      their respective impact on the improved outcome. Intensive insulin therapy
      effectively normalized blood glucose levels within 24 h, both in survivors and
      nonsurvivors. Intensive insulin therapy also increased serum levels of low
      density lipoprotein (P = 0.007) and high-density lipoprotein (P = 0.005), whereas
      it suppressed the elevated serum triglyceride concentrations (P < 0.0001).
      Multivariate logistic regression analysis, corrected for baseline univariate risk
      factors and the effect on inflammation, indicated that lipid rather than glucose
      control independently determined the beneficial effects of intensive insulin
      therapy on morbidity and mortality. In postmortem biopsies obtained from 74
      patients who died in the intensive care unit, intensive insulin therapy increased
      mRNA levels of skeletal muscle glucose transporter 4 (P = 0.02) and hexokinase (P
      = 0.03), unlike those of hepatic glucokinase. In conclusion, our data suggest
      that intensive insulin therapy normalizes blood glucose levels through
      stimulation of peripheral glucose uptake and concomitantly partially restores the
      abnormalities in the serum lipid profile, which may have contributed
      significantly to the improved outcome of protracted critical illness.

PMID- 14715854
TI  - A novel nonsense mutation of the mineralocorticoid receptor gene in a Swedish
      family with pseudohypoaldosteronism type I (PHA1).
AB  - Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting
      leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis.
      Sporadic cases and two familial forms, one autosomal dominant and one autosomal
      recessive form, have been described. The autosomal dominant or sporadic form
      manifests milder salt wasting that remits with age. Mutations in the gene
      encoding the mineralocorticoid receptor (MR) have been identified in patients
      with the autosomal dominant inheritance. However, recent studies suggest that the
      autosomal dominant and sporadic forms are genetically heterogeneous and that
      additional genes might be involved. We report on the study of 15 members of a
      Swedish five-generation family with the autosomal dominant form of PHA1.
      Interestingly, neuropathy was found in two of five affected individuals. A novel
      heterozygous nonsense mutation C436X in exon 2 was identified in the index
      patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis
      of the family demonstrated that the mutation segregated with PHA1 in the family.
      It is unclear whether the neuropathy is associated with the mutation found. Our
      results together with previously published data suggest that loss-of-function
      mutations of the MR gene located at 4q31.1, commonly are associated with the
      autosomal dominant form of PHA1.

PMID- 14715855
TI  - Low prevalence of the N363S polymorphism of the glucocorticoid receptor in South
      Asians living in the United Kingdom.
AB  - Similarities between clinical states of glucocorticoid excess and obesity have
      raised suspicion of a link between the two conditions. An Asn363Ser (N363S)
      polymorphism in exon 2 of the glucocorticoid receptor has been associated with
      glucocorticoid sensitivity and excess adiposity in people of European origin.
      Compared with Europid populations, South Asians have a higher prevalence of
      cardiovascular risk factors, including type 2 diabetes and central obesity. The
      aim of this study was to determine the prevalence of the 363S allele in people of
      South Asian origin living in northeast England in relation to obesity and other
      cardiovascular risk factors. DNA from 142 males and 153 females was characterized
      for 363S allele status. Two N363S heterozygotes were identified; both subjects
      had raised body mass index and central obesity. Despite a higher prevalence of
      overweight (body mass index >/==" BORDER="0"> 25 kg/m(2)) people in the South
      Asian group compared with the Europid population in the same geographical area
      (66 vs. 56%, respectively), the 363S allele frequency was significantly lower in
      the South Asian group (0.3 vs. 3%, respectively). Therefore, the N363S
      polymorphism is unlikely to be an important factor in obesity and/or dysmetabolic
      traits in people of South Asian origin living in the United Kingdom.

PMID- 14715856
TI  - In boys with abnormal developmental tempo, maturation of the skeleton and the
      hypothalamic-pituitary-gonadal axis remains synchronous.
AB  - The primary mechanism that initiates puberty is unknown. One possible clue is
      that pubertal maturation often parallels skeletal maturation. Conditions that
      delay skeletal maturation also tend to delay the onset of puberty, whereas
      conditions that accelerate skeletal maturation tend to hasten the onset of
      puberty. To examine this relationship, we studied boys with congenital adrenal
      hyperplasia (n = 13) and familial male-limited precocious puberty (n = 22), two
      conditions that accelerate maturational tempo, and boys with idiopathic short
      stature (n = 18) in which maturational tempo is sometimes delayed. In all three
      conditions, the onset of central puberty generally occurred at an abnormal
      chronological age but a normal bone age. Boys with the greatest skeletal
      advancement began central puberty at the earliest age, whereas boys with the
      greatest skeletal delay began puberty at the latest age. Furthermore, the
      magnitude of the skeletal advancement or delay matched the magnitude of the
      pubertal advancement or delay. This synchrony between skeletal maturation and
      hypothalamic-pituitary-gonadal axis maturation was observed among patients within
      each condition and also between conditions. In contrast, the maturation of the
      hypothalamic-pituitary-gonadal axis did not remain synchronous with other
      maturational processes including weight, height, or body mass index. We conclude
      that in boys with abnormal developmental tempo, maturation of the skeleton and
      the hypothalamic-pituitary-gonadal axis remains synchronous. This synchrony is
      consistent with the hypothesis that in boys, skeletal maturation influences
      hypothalamic-pituitary-gonadal axis maturation.

PMID- 14715857
TI  - Metformin therapy increases insulin-stimulated release of D-chiro-inositol
      containing inositolphosphoglycan mediator in women with polycystic ovary
      syndrome.
AB  - Some actions of insulin are mediated by putative inositolphosphoglycan mediators,
      and a deficiency in D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG)
      may contribute to insulin resistance in women with polycystic ovary syndrome
      (PCOS). Furthermore, similar effects of DCI and metformin, an insulin-sensitizing
      drug, have been demonstrated in PCOS women. To determine whether metformin
      improves insulin actions by increasing biologically active DCI-IPG in women with
      PCOS, we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women
      with PCOS before and after 4-8 wk of metformin or placebo. After treatment, the
      mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of
      insulin (AUC(insulin)) decreased significantly more in the metformin group,
      compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml
      (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG
      (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/-
      1021%/min, P = 0.60). However, the ratio of AUC(DCI-IPG)/AUC(insulin) increased
      by 160% after metformin and decreased by 29% after placebo (P = 0.002 between
      groups). Moreover, metformin seemed to improve the positive correlation between
      AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r
      = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo). We
      conclude that in obese women with PCOS, metformin may improve the action of
      insulin in part by improving insulin-mediated release of DCI-IPG mediators, as
      evidenced by increased bioactive DCI-IPG released per unit of insulin.

PMID- 14715858
TI  - Interleukin-1beta and tumor necrosis factor (TNF)-alpha sensitize human thyroid
      epithelial cells to TNF-related apoptosis-inducing ligand-induced apoptosis
      through increases in procaspase-7 and bid, and the down-regulation of p44/42
      mitogen-activated protein kinase activity.
AB  - Primary thyroid cells are resistant to TNF-related apoptosis-inducing ligand
      (TRAIL). Previously we showed that the combination of IL-1beta and TNFalpha
      facilitated TRAIL-mediated apoptosis in these cells and enhanced cell surface
      expression of TRAIL receptors. The aim of this study was to further characterize
      the mechanism by which these cytokines sensitized primary thyroid cells to TRAIL
      mediated apoptosis. IL-1beta and TNFalpha increased the concentrations of
      procaspase-7 and Bid. In contrast, the p44/42 MAPK (Erk) pathway was active in
      thyroid cells and this activity was significantly decreased after exposure to IL
      1beta/TNFalpha. A MAPK kinase inhibitor (U0126) could enhance the cytokine
      induced sensitization of thyroid cells to TRAIL, reinforcing the inhibitory role
      of Erk on TRAIL signaling. In conclusion, IL-1beta/TNFalpha treatment sensitizes
      human thyroid cells to TRAIL-mediated apoptosis through increased surface
      expression of TRAIL receptors, increased expression of procaspase-7 and Bid, and
      the inhibition of p44/42 MAPK (Erk) pathway.

PMID- 14715859
TI  - Simultaneous and continuous 24-hour plasma and cerebrospinal fluid leptin
      measurements: dissociation of concentrations in central and peripheral
      compartments.
AB  - The entrance of leptin into the central nervous system is of physiological
      relevance to the regulation of food intake, energy balance, and neuroendocrine
      function. To our knowledge, the relation between plasma and lumbar cerebrospinal
      fluid (CSF) leptin has not been examined across the 24-h period. To evaluate the
      relation between plasma and CSF leptin across the 24-h period, we studied
      simultaneous and continuous plasma and CSF leptin in nine subjects. We measured
      plasma and lumbar CSF leptin every 30 min for 24 h. All subjects had diurnal
      periodicity in 24-h plasma leptin levels, but not in CSF levels, as assessed by
      analysis of covariance and cosinor analysis. Plasma leptin had a significant 24-h
      pattern (P = 0.001), but CSF leptin did not. A 25-fold range of plasma leptin
      concentrations was reflected by a less-than-2-fold range in lumbar CSF leptin
      concentrations. Nocturnal increases in plasma leptin concentrations were not
      accompanied by commensurate changes in CSF values. It appears that leptin enters
      the brain by a mechanism that is highly saturable at physiological leptin
      concentrations and that the dynamics of plasma leptin is not accompanied by
      similar dynamics in CSF leptin measured at the lumbar spinal level. Therefore, it
      is not possible to use plasma leptin levels to predict lumbar CSF leptin
      concentrations. Although we acknowledge that lumbar CSF concentrations do not
      fully reflect the dynamics of leptin in the brain, we suggest that the nocturnal
      saturability of leptin transport into the central nervous system might help
      explain the lack of responsiveness to the central physiologic effects of leptin
      in states of hyperleptinemia, such as obesity.

PMID- 14715860
TI  - Low central nervous system serotonergic responsivity is associated with the
      metabolic syndrome and physical inactivity.
AB  - The metabolic syndrome, recognized by the co-occurrence of general or abdominal
      obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears
      to involve disturbances in metabolism, autonomic function, and health-related
      behaviors. However, physiological processes linking the components of the
      metabolic syndrome remain obscure. The current study examined associations of
      central nervous system serotonergic function with each metabolic syndrome risk
      variable, the metabolic syndrome, and physical activity. The subjects were 270
      adult volunteers who participated in a study of cardiovascular disease risk
      factors and neurobehavioral functioning. Central serotonergic responsivity was
      indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent,
      fenfluramine. Across the sample, low PRL response was associated with greater
      body mass index, higher concentrations of triglycerides, glucose, and insulin,
      higher systolic and diastolic blood pressure, greater insulin resistance, and
      less physical activity (P < 0.03-0.001). There also existed an inverse linear
      relationship between PRL response and the number of metabolic syndrome risk
      factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in
      PRL response was associated with an odds ratio for the metabolic syndrome of 2.05
      (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence
      interval, 1.69-19.25; P = 0.005), according to the definitions of the National
      Cholesterol Education Program and the World Health Organization, respectively.
      These findings reveal a heretofore unrecognized association between reduced
      central serotonergic responsivity and the metabolic syndrome.

PMID- 14715861
TI  - Retinoic acid and retinoid X receptors are differentially expressed in thyroid
      cancer and thyroid carcinoma cell lines and predict response to treatment with
      retinoids.
AB  - Therapy for patients with advanced thyroid carcinoma is limited. Clinical and in
      vitro studies suggest that some patients with advanced thyroid cancer may respond
      to therapy with retinoic acid. mRNA expression of the six retinoic acid (RAR) and
      retinoid X receptor (RXR) isoforms (RARalpha, -beta, -gamma and RXRalpha, -beta, 
      gamma) was measured in four human thyroid cell lines, and protein expression was
      subsequently measured in 10 thyroid cancer cell lines. Two isoforms, RARbeta and
      RXRgamma, were differentially expressed in the four cell lines. Comparison of 10
      thyroid tumors and matched normal thyroid tissue confirmed differential tumor
      expression of RARbeta and RXRgamma and lack of the RXRgamma isoform in normal
      thyroid tissue. Cell lines expressing both RARbeta and RXRgamma demonstrated
      significant growth suppression when treated with retinoids, whereas cell lines
      lacking these isoforms were unaffected. Expression of RARbeta, the isoform
      associated with suppression of tumor growth in other cancer types, was not
      affected by treatment with retinoids in the thyroid cancer cell lines. LG346
      increased apoptosis and decreased cells in the S-phase in an anaplastic carcinoma
      cell line, suggesting that this retinoid causes growth suppression of these cells
      by multiple mechanisms. In summary, we identified the RARbeta and RXRgamma
      isoform to be differentially expressed in thyroid cancer cell lines and tumor
      tissue. These isoforms seem to predict response to retinoid therapy in thyroid
      cancer cell lines.

PMID- 14715862
TI  - Association of 24-hour cortisol production rates, cortisol-binding globulin, and
      plasma-free cortisol levels with body composition, leptin levels, and aging in
      adult men and women.
AB  - The present study was designed to examine the hypothesis that hypothalamic
      pituitary-adrenal axis activity as measured by 24-h cortisol production rate
      (CPR) and plasma levels of free cortisol is linked to increased body fat in
      adults, and that increased cortisol levels with aging results from increased CPR.
      Fifty-four healthy men and women volunteers with a wide range of body mass
      indexes and ages underwent measurement of CPR by isotope dilution measured by gas
      chromatography-mass spectroscopy, cortisol-binding globulin, and free cortisol in
      pooled 24-h plasma, body composition, and leptin. Cortisol clearance rates were
      determined from the 10-h disappearance curves of hydrocortisone after steady
      state infusion in a separate group of lean and obese subjects with adrenal
      insufficiency. Although CPR significantly increased with increasing body mass
      index and percentage body fat, free cortisol levels remained independent of body
      composition and leptin levels due to increased cortisol clearance rates. CPR and
      free cortisol levels were, however, significantly higher in men than women. In
      addition, 24-h plasma free cortisol levels were increased with age in association
      with increased CPR, independent of body size. This increase in hypothalamic
      pituitary-adrenal axis activity may play a role in the alterations in body
      composition and central fat distribution in men vs. women and with aging.

PMID- 14715863
TI  - Preoperative evaluation of infants with focal or diffuse congenital
      hyperinsulinism by intravenous acute insulin response tests and selective
      pancreatic arterial calcium stimulation.
AB  - Infants with congenital hyperinsulinism often require pancreatectomy. Recessive
      mutations of the ATP-dependent plasma membrane potassium channel (K(ATP)) genes,
      SUR1 and K(ir)6.2, cause diffuse hyperinsulinism. K(ATP) channel mutations can
      also cause focal disease through loss of heterozygosity for maternal 11p,
      resulting in expression of a paternal mutation. This study evaluated whether
      focal vs. diffuse hyperinsulinism could be diagnosed by acute insulin response
      (AIR) tests and whether arterial calcium stimulation/venous sampling (ASVS) could
      localize focal lesions. Fifty infants with diazoxide-unresponsive hyperinsulinism
      were studied. Focal lesions occurred in 70% of the cases. Positive AIR calcium
      occurred in 17 of 30 focal and 10 of 13 diffuse cases (P < 0.04). Positive AIR
      tolbutamide occurred in 27 of 30 focal vs. seven of 13 diffuse cases (P < 0.02);
      K(ATP) channel mutations were identified in four of the latter. ASVS localized
      the lesion in 24 of 33 focal cases (73%) but correctly diagnosed diffuse disease
      in only four of 13 cases. These results indicate that preoperative AIR tests do
      not distinguish focal vs. diffuse disease because some K(ATP) channel mutations
      retain responsiveness to tolbutamide. The ASVS test can be used to localize focal
      lesions in infants. The combination of ASVS, careful intraoperative histologic
      analysis, and surgical expertise succeeded in correcting hypoglycemia in 86% of
      the infants with focal hyperinsulinism.

PMID- 14715864
TI  - The insulin secretagogues glibenclamide and repaglinide do not influence growth
      hormone secretion in humans but stimulate glucagon secretion during profound
      insulin deficiency.
AB  - In vitro data have recently suggested that sulfonylureas (SUs) enhance GH
      secretion by modulating the effects of GHRH and somatostatin in pituitary cells.
      The present study was undertaken to explore in more detail a possible influence
      of a single dose of SU (glibenclamide) and a non-SU (repaglinide) insulin
      secretagogue on circulating GH dynamics. Ten C-peptide-negative type 1 diabetic
      individuals were examined on three occasions in random order. Either
      glibenclamide (10.5 mg), repaglinide (8 mg), or placebo was administered after
      overnight normalization of plasma glucose by iv insulin infusion. Subsequently,
      GH concentrations were measured regularly after stimulation with GHRH (bolus 0.1
      micro g/kg) alone and during concomitant infusion with somatostatin (7 ng.kg(
      1).min(-1)). Insulin was replaced at baseline levels (0.25 mU.kg(-1).min(-1)) and
      plasma glucose clamped at 5-6 mmol/liter. Overall, there were no significant
      statistical differences in GH responses determined as either GH peak
      concentrations, integrated levels of GH, or secretory burst mass of GH during the
      experimental protocol. In contrast, plasma glucagon concentrations were
      significantly increased during glibenclamide and repaglinide exposure. The
      present experimental design does not support the hypothesis that acute
      administration of pharmacological doses of the oral antihyperglycemic agents
      glibenclamide and repaglinide per se enhance GH release in humans. Additionally,
      this study shows that these potassium channel inhibitors seem to stimulate
      glucagon secretion in people who have severe intraislet insulin deficiency (e.g.
      type 1 diabetes). However, extrapolation of our findings to type 2 diabetic
      individuals should be done with some caution.

PMID- 14715865
TI  - Height in pre- and postmenopausal women is influenced by estrogen receptor alpha
      gene polymorphisms.
AB  - The estrogen receptor alpha gene (ESR1) is known to be involved in metabolic
      pathways influencing growth. We have performed two population-based association
      studies using three common polymorphisms within this candidate gene to determine
      whether these are associated with variation in adult stature. In 607 women, aged
      55-80 yr, from the Rotterdam Study, the ESR1 PvuII-XbaI haplotype 1 (px) and the
      L allele of the TA repeat polymorphism (<18 TA repeats) were significantly
      associated with an allele dose-dependent decrease in height. The per allele copy
      of ESR1 PvuII-XbaI haplotype 1 height was 0.9 cm shorter (P trend = 0.02) and 1.0
      cm/allele copy of the TA repeat L allele (P trend = 0.003). These results were
      independent of age, age at menarche and menopause, and lumbar spine bone mineral
      density and remained significant after participants with vertebral fractures were
      excluded. In 483 men from the Rotterdam Study we found no association with
      height. In 1500 pre- and perimenopausal women from the Eindhoven Study a similar
      association was observed; women were 0.5 cm shorter per allele copy of the ESR1
      haplotype 1 (P for trend = 0.03). In conclusion, we demonstrate a role for
      genetic variations in the estrogen receptor alpha gene in determining adult
      stature in women.

PMID- 14715866
TI  - Lack of support for a role of the insulin gene variable number of tandem repeats
      minisatellite (INS-VNTR) locus in fetal growth or type 2 diabetes-related
      intermediate traits in United Kingdom populations.
AB  - The insulin gene variable number of tandem repeats minisatellite (INS-VNTR) class
      III allele is associated with altered fetal growth, type 2 diabetes risk
      (especially when paternally inherited), and insulin and IGF2 gene expression.
      Further studies are needed to establish the role of the INS-VNTR in fetal growth
      and assess whether its effects depend on the parent of origin. We analyzed the
      INS-VNTR-linked -23 Hph1 polymorphism in 2283 subjects, comprising 1184 children
      and 1099 parents. There were no differences (P < 0.05) in birth weight between
      offspring of the three genotypes: III/III (n = 108) vs. I/I (n = 558), effect
      size, -8 g (P = 0.87); and I/III (n = 464) vs. I/I, effect size, -19 g (P =
      0.54). We observed no differences in head circumference [III/III (n = 95) vs. I/I
      (n = 470), effect size, -0.14 cm; P = 0.31] or birth length. No differences were
      observed when stratifying by postnatal growth realignments [nonchangers III/III
      (n = 37) vs. I/I (n = 170), effect size, -43 g; P = 1.00] or by parent of origin
      of the class III allele (presence of paternal III allele effect size, -15 g; P =
      0.74). INS-VNTR was nominally associated (P < 0.05) with body mass index and
      insulin resistance, but not with beta-cell function, in young adults. In the
      largest study to date, we found a lack of support for a role for INS-VNTR in
      fetal growth and nominal association with type 2 diabetes-related intermediate
      traits.

PMID- 14715867
TI  - Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory
      women of reproductive age.
AB  - Anti-Mullerian hormone (AMH) concentrations correlate with the number of antral
      follicles as well as age and constitute an endocrine marker for ovarian aging. In
      normogonadotropic anovulatory infertile women [World Health Organization (WHO)
      class 2], the number of early antral follicles is usually increased. To
      investigate whether AMH concentrations are increased, serum levels in 128 WHO 2
      women were compared with those in 41 normoovulatory premenopausal women of
      similar age. Serum AMH concentrations are significantly (P < 0.001) elevated in
      WHO 2 patients [median, 7.6 micro g/liter (range, 0.1-40.0)], compared with
      controls [median, 2.1 micro g/liter (0.1-7.4)]. In 106 patients presenting with
      polycystic ovaries (PCOs) (>/==" BORDER="0">12 follicles/ovary measuring 2-9 mm
      and/or an ovarian volume > 10 ml), AMH levels were elevated [9.3 micro g/liter
      (1.8-40.0)], compared with 22 patients without PCOs [6.4 micro g/liter (0.1
      22.1)] (P < 0.0001). In WHO 2 patients, AMH concentrations correlated with
      features characteristic for polycystic ovary syndrome such as LH concentrations
      (r = 0.331; P = 0.0001), testosterone levels (r = 0.477, P = 0.0001), mean
      ovarian volume (r = 0.421; P = 0.0001), and the number of ovarian follicles (r =
      0.308; P = 0.0001). AMH levels correlated well with age in WHO 2 patients (r = 
      0.248; P = 0.002) as well as in controls (r = -0.465; P = 0.005). However, the
      relative decline in AMH with age is less pronounced in WHO 2 patients. In a
      subset of patients no significant correlation was found between AMH serum
      concentrations and the FSH response dose, the duration of stimulation, and the
      total number of ampoules of FSH used. In conclusion, serum AMH concentrations are
      elevated in WHO 2 women, especially in those patients exhibiting PCOs. Because
      AMH concentrations correlated well with other clinical, endocrine, and ultrasound
      markers associated with polycystic ovary syndrome, AMH may be used as a marker
      for the extent of the disease. A less pronounced AMH decrease over time in these
      women may suggest retarded ovarian aging. The latter hypothesis, however, should
      be confirmed by longitudinal studies.

PMID- 14715868
TI  - Phosphodiesterase 4 inhibition synergizes with relaxin signaling to promote
      decidualization of human endometrial stromal cells.
AB  - The decidualization of endometrial stromal cells in the secretory phase of the
      menstrual cycle is an essential prerequisite for the implantation of a
      blastocyst. This profound differentiation process is accompanied by sustained
      elevated intracellular cAMP concentrations in vivo. Primary cell cultures of
      endometrial stromal cells decidualize by treatment with cAMP-elevating agents in
      vitro. Our previous findings indicated that the cAMP-degrading activities of
      phosphodiesterases (PDE) and signaling of the peptide hormone relaxin are coupled
      in human endometrial stromal cells. In the present study we have chosen a
      pharmacological approach to test whether relaxin binding and PDE inhibition
      cooperate to induce decidualization. Measurement of PDE activity and relaxin
      stimulated cAMP accumulation in the presence of diverse PDE inhibitors identified
      PDE4 and PDE8 as the principal PDE isoforms involved in human endometrial stromal
      cells. The PDE4 inhibitor rolipram was most effective in elevating intracellular
      cAMP concentrations and synergizing with relaxin to achieve maximal in vitro
      decidualization, as determined by measurement of the expression of the decidual
      marker genes for prolactin and IGF-binding protein-1 and measurement of prolactin
      secretion. Gene expression for PDE4D and PDE4C was significantly up-regulated
      during in vitro decidualization. Treatment of cell cultures with the protein
      kinase A inhibitor H89 revealed a minor role for protein kinase A-mediated
      positive feedback control of PDE4 activity in human endometrial stromal cells,
      consistent with sustained elevated cAMP essential for decidualization in vitro.
      These findings introduce the new idea of clinically applying the combination of a
      specific PDE4 inhibitor with an effector such as relaxin, thereby offering an
      alternative nonsteroidal luteal phase support for the endometrium to encourage
      endometrial development and implantation in subfertile women undergoing assisted
      reproductive technology procedures.

PMID- 14715869
TI  - Ghrelin levels are not regulated by recombinant leptin administration and/or
      three days of fasting in healthy subjects.
AB  - Ghrelin, a stomach-derived orexigenic peptide, and leptin, a fat-derived
      anorexigenic hormone, act primarily in the hypothalamus to regulate energy
      homeostasis and have been reported to be regulated in opposite directions by
      acute and chronic changes in nutritional state. Nutritional, anthropometric, and
      hormonal predictors of circulating ghrelin have not yet been fully elucidated,
      and whether ghrelin is regulated by leptin in humans remains unknown. To address
      these questions, we performed cross-sectional and interventional studies. In 120
      healthy men and women, ghrelin was negatively associated with leptin as well as
      overall and central adiposity, but not with total energy or specific
      macronutrient intake. The sexual dimorphism in ghrelin levels (higher levels in
      women than in men) and the negative correlation between ghrelin and insulin are
      largely mediated by central adiposity. In six lean men, complete fasting for 3 d
      resulted in a low leptin state without a major change in fat mass and abolished
      the meal-related secretory pattern of ghrelin without increasing 24-h ghrelin
      levels. In addition, recombinant human leptin administration in physiological and
      pharmacological doses did not regulate ghrelin over several hours to a few days.
      These data do not support a role for regulation of circulating ghrelin by leptin
      levels independently of changes in adiposity and suggest that the leptin and
      ghrelin systems for energy homeostasis function independently of each other in
      healthy humans.

PMID- 14715870
TI  - Polymorphisms in the P450 c17 (17-hydroxylase/17,20-Lyase) and P450 c19
      (aromatase) genes: association with serum sex steroid concentrations and bone
      mineral density in postmenopausal women.
AB  - The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase,
      respectively, both involved in sex hormone synthesis. We investigated the
      association between 2 common polymorphisms in 1) the promoter region (T-->C
      substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density
      (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal
      women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in
      serum estradiol concentrations between cases (n = 136) and controls (n = 116).
      The CYP 19 genotype was significantly associated with serum estradiol (P =
      0.002). Women with the AA genotype had higher serum estradiol concentrations
      compared with those with the GG genotype (P = 0.03). In older women, those with
      the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P =
      0.04) and fractures (P = 0.003). We found no significant association between CYP
      17 genotype and serum androgens and estradiol concentrations. However, a
      significant association was seen between BMD values at the femoral neck with CYP
      17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012).
      Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7
      +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and
      CYP 19 are candidate genes for osteoporosis in postmenopausal women.

PMID- 14715871
TI  - A coated tube assay for the detection of blocking thyrotropin receptor
      autoantibodies.
AB  - We developed a coated tube assay to discriminate TSH-receptor-stimulating
      autoantibodies [thyroid-stimulating antibodies (TSAb)] from those autoantibodies
      blocking TSH binding without intrinsic activation [thyroid-blocking antibodies
      (TBAb)]. The wild-type TSH receptor in the TSH binding-inhibitory assay was
      exchanged for a chimeric receptor where a TSAb epitope (amino acids 8-165) was
      replaced by comparable LH-R residues. Binding of (125)I-labeled TSH to this
      chimera could be inhibited by sera containing TBAb up to 95%. Sera from 316
      patients with Graves' disease and 17 with autoimmune thyroid disease were grouped
      according to their bioassay activity. At the decision threshold, the chimera A
      assay had a sensitivity of 78.0% for TBAb with a specificity of 90.2%. In detail,
      19 of 22 (86.4%) TBAb sera and 15 of 23 (65.2%) TSAb/TBAb sera were positive but
      only 32 of 216 (14.0%) TSAb sera and 5 of 72 (6.9%) bioassay negative sera. There
      was a weak but significant positive correlation (r = 0.46) between the chimera
      assay and the bioassay for TBAb. This is the first report of a coated tube assay
      for the determination of TBAb employing an adaptation of the TSH binding
      inhibitory format, which could be a useful alternative to the bioassay.

PMID- 14715872
TI  - Mutations in the seipin and AGPAT2 genes clustering in consanguineous families
      with Berardinelli-Seip congenital lipodystrophy from two separate geographical
      regions of Brazil.
AB  - Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by a near
      total congenital absence of fat and predisposition to develop diabetes mellitus.
      In this study, we investigated the presence of mutations in the Seipin and 1
      acylglycerol phosphate acyltransferase 2 (AGPAT2) genes in 32 affected subjects
      with BSCL from 17 consanguineous pedigrees living in two separate geographical
      regions, the northeastern and southeastern regions, of Brazil. All, except one,
      of the 22 BSCL subjects from 15 families living in the northeastern region were
      found to have a homozygous 669insA mutation in the Seipin gene. In contrast, all
      10 BSCL subjects from two families living in the southeastern region were found
      to a have a homozygous 1036-bp deletion including exons 3 and 4 of AGPAT2. These
      results support genetic heterogeneity among BSCL patients in Brazil. Our finding
      of a single mutation in the Seipin and AGPAT2 genes in the pedigrees from the
      northeastern and southeastern regions, respectively, will be useful in genetic
      counseling of subjects from these large pedigrees from Brazil.

PMID- 14715873
TI  - A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial
      malignant sympathetic extraadrenal paragangliomas.
AB  - We report a family with malignant sympathetic paragangliomas (PGL) exhibiting a
      new type of germline mutation in the succinate dehydrogenase subunit B (SDHB)
      gene. Two affected brothers, presenting with symptoms at the ages of 25 and 52
      yr, suffered from malignant abdominal extraadrenal sympathetic PGL. They died of
      their disease at ages 43 and 61 yr. Their mother had the same history of signs
      and symptoms, suggesting a catecholamine-producing tumor at the age of 55 yr.
      Analysis of the germline DNA from these three patients revealed a novel mutation
      in exon 4 (H132P) of the SDHB gene. This mutation was absent in 160 control
      chromosomes. Loss of heterozygosity analysis of the tumors showed a loss of one
      SDHB allele, and RT-PCR-based expression analysis confirmed the exclusive
      expression of the mutated allele in both tumors. A review of the published PGL
      families revealed malignant tumors in seven of 12 well-documented families with
      SDHB mutation-associated extraadrenal PGL. These findings, as well as findings of
      the family reported here, suggest a strong causal relationship of SDHB germline
      mutations with malignant extraadrenal abdominal PGL and imply the necessity of a
      close follow-up of affected individuals and family members.

PMID- 14715874
TI  - Molecular genetic analysis of Tunisian patients with a classic form of 21
      hydroxylase deficiency: identification of four novel mutations and high
      prevalence of Q318X mutation.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine
      the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was
      analyzed in 51 unrelated patients using our cascade strategy (digestion by
      restriction enzyme, sequencing). All patients had a classical form of 21
      hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes
      examined. The most frequent mutation in the Tunisian CAH population was found to
      be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in
      other series. Incidence of other mutations does not differ, as previously
      described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N
      (10.8%). Four novel mutations were found in four patients with the salt-wasting
      form. These four novel mutations include three point mutations that have not been
      reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small
      conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good
      genotype/phenotype correlation in the case of most mutations. This is the first
      report of screening for mutations of 21-hydroxylase gene in the Tunisian
      population and even in the Arab population.

PMID- 14715875
TI  - Differential recruitment of coregulator proteins steroid receptor coactivator-1
      and silencing mediator for retinoid and thyroid receptors to the estrogen
      receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in
      human breast cancer.
AB  - Estrogen receptor (ER)-alpha and ER-beta function as transcription factors, and
      both interact with nuclear regulatory proteins to enhance or inhibit
      transcription. We hypothesized that coregulators are expressed in breast cancer
      and may be differentially recruited by ERs in the presence of estrogen and
      tamoxifen. ER-beta was found to be expressed more frequently in node-negative
      patients (P < 0.05). Expression of steroid receptor coactivator-1 (SRC-1) was
      associated with nodal positivity (P < 0.05) and resistance to endocrine treatment
      (P < 0.001). The spatial coexpression of ER-alpha, ER-beta, and the coregulatory
      proteins was established using immunofluorescence. In both cell lines (MCF-7 and
      T47D) and in primary breast cancer cell cultures, beta-estradiol up-regulated ER
      beta and coregulator protein expression and increased ER-alpha/ER-beta
      interaction with the estrogen response element (ERE). 4- Hydroxy-tamoxifen (4
      OHT) increased ER-alpha and silencing mediator for retinoid and thyroid receptors
      (SMRT) expression and increased ER-ERE binding. SRC-1 and SMRT were identified at
      the ER-ERE complex, and interactions between ER isoforms and coregulatory
      proteins were determined using immunoprecipitation. Both ER-alpha and ER-beta
      preferentially bound SRC-1 in the presence of beta-estradiol. Conversely, in
      cells treated with 4-OHT, ER-alpha and ER-beta bound SMRT. Differential
      recruitment of SRC-1 and SMRT by ER-alpha and ER-beta in the presence of beta
      estradiol and 4-OHT may be central to the response of the tumor to endocrine
      treatment.

PMID- 14715876
TI  - A longitudinal study of intrauterine growth and the placental growth hormone (GH)
      insulin-like growth factor I axis in maternal circulation: association between
      placental GH and fetal growth.
AB  - The aim of the study was 1) to evaluate the association of maternal serum levels
      of placental GH and IGF-I with fetal growth, and 2) to establish reference data
      for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal
      pregnancies based on longitudinal measurements. A prospective longitudinal study
      of 89 normal pregnant women was conducted. The women had, on the average, seven
      blood samples taken and three ultrasound examinations performed. All had normal
      umbilical artery pulsatility indexes during pregnancy and gave birth to
      singletons between 37 and 42 wk gestation with birth weights above -2 SD.
      Placental GH levels were detectable in all samples from as early as 5 wk
      gestation and increased significantly throughout pregnancy to approximately 37 wk
      when peak levels of 22 ng/ml (range, 4.64-69.22 ng/ml) were reached.
      Subsequently, placental GH levels decreased until birth. The change in placental
      GH during 24.5-37.5 wk gestation was positively associated with fetal growth rate
      (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH
      values (P = 0.007) was associated with pregnancy length. A positive association
      between the change in placental GH and the change in IGF-I levels throughout
      gestation was found in a multivariate analysis (r(2) = 0.42; P < 0.001). There
      was no association between placental GH and IGFBP-3 levels. The change in IGF-I
      throughout gestation (P = 0.039), but not placental GH, was significantly
      positively associated with placental weight at birth. We found a significant
      association between placental GH and fetal growth. In addition, we found a highly
      significant association between the increase in placental GH and the increase in
      IGF-I. The gestational age at peak placental GH levels was associated with
      pregnancy length.

PMID- 14715877
TI  - Genetic and structural evaluation of fatty acid transport protein-4 in relation
      to markers of the insulin resistance syndrome.
AB  - Disturbances in fatty acid metabolism are involved in the etiology of insulin
      resistance and the related dyslipidemia, hypertension, and procoagulant state.
      The fatty acid transport proteins (FATPs) are implicated in facilitated cellular
      uptake of nonesterified fatty acids (NEFAs), thus potentially regulating NEFA
      concentrations and metabolism. The aim of this study was to investigate
      polymorphic loci in the FATP4 gene with respect to associations with fasting and
      postprandial lipid and lipoprotein variables and markers of insulin resistance in
      608 healthy, middle-aged Swedish men and to evaluate possible mechanisms behind
      any associations observed. Heterozygotes for a Gly209Ser polymorphism (Ser allele
      frequency 0.05) had significantly lower body mass index and, correcting for body
      mass index, significantly lower triglyceride concentrations, systolic blood
      pressure, insulin concentrations, and homeostasis model assessment index compared
      with common homozygotes. A three-dimensional model of the FATP4 protein based on
      structural and functional similarity with adenylate-forming enzymes revealed that
      the variable residue 209 is exposed in a region potentially involved in protein
      protein interactions. Furthermore, the model indicated functional regions with
      respect to NEFA transport and acyl-coenzyme A synthase activity and membrane
      association. These findings propose FATP4 as a candidate gene for the insulin
      resistance syndrome and provide a structural basis for understanding FATP
      function in NEFA transport and metabolism.

PMID- 14715878
TI  - Expression of ghrelin and its functional receptor, the type 1a growth hormone
      secretagogue receptor, in normal human testis and testicular tumors.
AB  - Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), has been
      primarily linked to the central neuroendocrine regulation of GH secretion and
      food intake, although additional peripheral actions of ghrelin have also been
      reported. In this context, the expression of ghrelin and its cognate receptor has
      been recently demonstrated in rat testis, suggesting a role for this molecule in
      the direct control of male gonadal function. However, whether this signaling
      system is present in human testis remains largely unexplored. In this study we
      report the expression and cellular location of ghrelin and its functional
      receptor, the type 1a GHS-R, in adult human testis. In addition, evaluation of
      ghrelin and GHS-R1a immunoreactivity in testicular tumors and dysgenetic tissue
      is presented. The expression of the mRNAs encoding ghrelin and GHS-R1a was
      demonstrated in human testis specimens by RT-PCR, followed by direct sequencing.
      In normal testis, ghrelin immunostaining was demonstrated in interstitial Leydig
      cells and, at lower intensity, in Sertoli cells within the seminiferous tubules.
      In contrast, ghrelin was not detected in germ cells at any stage of
      spermatogenesis. The cognate ghrelin receptor showed a wider pattern of cellular
      distribution, with detectable GHS-R1a protein in germ cells, mainly in pachytene
      spermatocytes, as well as in somatic Sertoli and Leydig cells. Ghrelin
      immunoreactivity was absent in poorly differentiated Leydig cell tumor, which
      retained the expression of GHS-R1a peptide. In contrast, highly differentiated
      Leydig cell tumors expressed both the ligand and the receptor. The expression of
      ghrelin and GHS-R1a was also detected in dysgenetic Sertoli cell-only
      seminiferous tubules, whereas germ cell tumors (seminoma and embryonal carcinoma)
      were negative for ghrelin and were weakly positive for GHS-R1a. In conclusion,
      our results demonstrate that ghrelin and the type 1a GHS-R are expressed in adult
      human testis and testicular tumors. Overall, the expression of ghrelin and its
      functional receptor in human and rat testis, with roughly similar patterns of
      cellular distribution, is highly suggestive of a conserved role for this newly
      discovered molecule in the regulation of mammalian testicular function.

PMID- 14715879
TI  - Inhibition of nuclear factor-kappaB cascade potentiates the effect of a
      combination treatment of anaplastic thyroid cancer cells.
AB  - Nuclear transcription factor-kappaB (NF-kappaB) is a transcriptional complex that
      is rapidly activated in the course of an immediate early response of cells after
      exposure to different stresses including ionizing radiation (IR). To overcome the
      limitation of radiation therapy for thyroid cancers, we studied the response of
      the NF-kappaB cascade to IR in cultured normal human thyroid cells and various
      thyroid cancer cell lines. Exposure to IR resulted in a dose-dependent increase
      of DNA-binding activity of p65 and p50 subunits in all types of thyroid cells.
      Specific inhibitors of NF-kappaB or phosphorylation deficient mutant inhibitory
      protein IkappaBalpha reduced thyroid cancer cell survival after exposure to IR
      and enhanced IR-induced cell death in a model undifferentiated thyroid cancer
      cell line. Tumors harboring mutant IkappaBalpha implanted into nude mice
      exhibited delayed growth rate and increased radiosensitivity. Terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling
      and annexinV-propidium iodide staining revealed the increase of radiation-induced
      apoptosis in the cells with inhibited NF-kappaB signaling. Our results indicate
      that radiosensitivity of transformed thyroid cells is due in part to elevated
      basal activity and rapid induction of the active form of NF-kappaB. We therefore
      suggest that inhibition of NF-kappaB could be an effective modality for radiation
      therapy of advanced human thyroid cancers.

PMID- 14715880
TI  - Behavioral and physical masculinization are related to genotype in girls with
      congenital adrenal hyperplasia.
AB  - Girls with congenital adrenal hyperplasia (CAH) exhibit behavioral
      masculinization. There is controversy about the roles of pre- and postnatal
      androgens, social factors, and chronic illness in its etiology. To assess the
      effect of chronic illness, we compared behavioral masculinity in 24 CAH girls and
      25 diabetic girls aged 3-12 yr from Manchester using two sensitive
      questionnaires, and an overall masculinity score M (high = masculine) was
      derived. To assess the contributions of pre- and postnatal androgens, the CAH
      subjects were categorized into genotype groups (G) according to the reported
      severity of loss of CYP21 function: G1 (n = 10, null mutations), G2 (n = 9,
      intron 2G), G3 (n = 3, I172N), and G4 (n = 2, unknown loss of function). In CAH
      girls, relationships between G, Prader degree of genital masculinization at
      birth, bone age advance, and M were assessed. CAH girls were less feminine and
      more masculine than diabetic girls (P < 0.001), who were not significantly
      different from U.S. controls. Among the CAH girls, those in G1 and 2 were more
      genitally masculinized than those in G3 and 4 (P < 0.009) and had higher M (P <
      0.025). M was negatively correlated with advanced bone age (r = -0.5; P = 0.02).
      CAH girls, but not diabetic girls, demonstrated behavioral masculinization. Both
      physical and behavioral masculinization were related to each other and to
      genotype, indicating that behavioral masculinization is a consequence of prenatal
      androgen exposure.

PMID- 14715881
TI  - Insulin-like growth factor I has a direct effect on glucose and protein
      metabolism, but no effect on lipid metabolism in type 1 diabetes.
AB  - There is evidence of a metabolic role for IGF-I in type 1 diabetes, but it is
      unclear whether IGF-I acts indirectly by reducing GH secretion or has direct
      effects. Using stable isotopes we have investigated, on three separate occasions,
      the effect of a pulse of recombinant human GH, a sc injection of recombinant
      human IGF-I, and a placebo on glucose, lipid, and protein metabolism in subjects
      with type 1 diabetes during a basal insulin infusion and a hyperinsulinemic
      euglycemic clamp. Endogenous GH secretion was suppressed with octreotide. IGF-I
      reduced the hepatic glucose production rate (Ra), increased peripheral glucose
      uptake, and reduced protein breakdown during the basal insulin infusion (P <
      0.05, P < 0.005, and P < 0.05, respectively, vs. placebo) and the
      hyperinsulinemic euglycemic clamp (P < 0.05, P < 0.005, and P < 0.05,
      respectively, vs. placebo). IGF-I had no effect on glycerol Ra, an index of
      lipolysis. GH increased glucose and glycerol Ra during the basal insulin infusion
      (P < 0.005 vs. placebo study), but the effects were no different from placebo
      during the clamp. In conclusion, IGF-I had a direct effect on glucose and protein
      metabolism, which was maintained during the hyperinsulinemic euglycemic clamp.
      This suggests that IGF-I acts in concert with insulin and may have an important
      role in maintaining glucose homeostasis and protein metabolism in type 1
      diabetes.

PMID- 14715882
TI  - Phantoms in the assay tube.

PMID- 14715884
TI  - The ABRF-MIRG'02 study: assembly state, thermodynamic, and kinetic analysis of an
      enzyme/inhibitor interaction.
AB  - Fully characterizing the interactions involving biomolecules requires information
      on the assembly state, affinity, kinetics, and thermodynamics associated with
      complex formation. The analytical technologies often used to measure biomolecular
      interactions include analytical ultracentrifugation (AUC), isothermal titration
      calorimetry (ITC), and surface plasmon resonance (SPR). In order to evaluate the
      capabilities of core facilities to implement these technologies, the Association
      of Biomolecular Resource Facilities (ABRF) Molecular Interactions Research Group
      (MIRG) developed a standardized model system and distributed it to a panel of
      AUC, ITC, and SPR operators. The model system was composed of a well
      characterized enzyme-inhibitor pair, namely bovine carbonic anhydrase II (CA II)
      and 4-carboxybenzenesulfonamide (CBS). Study participants were asked to measure
      one or more of the following: (1) the molecular mass, homogeneity, and assembly
      state of CA II by AUC; (2) the affinity and thermodynamics for complex formation
      by ITC; and (3) the affinity and kinetics of complex formation by SPR. The
      results from this study provide a benchmark for comparing the capabilities of
      individual laboratories and for defining the utility of the different
      instrumentation.

PMID- 14715885
TI  - Capillary DNA sequencing: maximizing the sequence output.
AB  - Like most other DNA sequencing core facilities, one of our continuing goals is to
      improve our sequence output without substantially adding to cost. To minimize
      sample-to-sample variability in template DNA concentration, we implemented the
      rolling circle amplification (RCA) procedure for preparing our DNA templates. In
      addition to saving time and reducing the number of steps in template DNA
      preparation, the RCA method has the potential to normalize the DNA concentration
      in samples that can be sequenced directly without additional purification. In the
      present study, we used RCA-generated templates to test a recently reported
      procedure that increased sequence quality by resuspending the sequenced products
      in low concentrations of agarose before capillary electrophoresis (CE) on a
      MegaBACE 1000 platform. Although we did not obtain the expected result using the
      specified procedure, a modification resulted in up to 60% increase in total
      sequence yield per sample plate. A combination of agarose and formamide-EDTA in
      the resuspension solution enabled us to generate long-read and high-quality
      sequences for more than 38,000 templates with minimal additional cost.

PMID- 14715886
TI  - ABRF-ESRG'03: analysis of a PVDF-bound known protein with a homogeneous amino
      terminus.
AB  - The Association of Biomolecular Resource Facilities 2003 Edman Sequencing
      Research Group (ABRF-ESRG'03) sample is the 15th in a series of studies designed
      to allow participating members to evaluate their abilities to analyze the N
      terminus of a protein or peptide using automated Edman degradation chemistry. It
      is a follow-up study to the ESRG'02 sample, which was a single protein with a
      heterogeneous N-terminus. Both the 2002 and 2003 samples were obtained from the
      same protein complex and were resolved by SDS-PAGE followed by electrophoretic
      transfer to PVDF membrane. The ABRF-ESRG'03 sample had an apparent molecular
      weight of 49 kDa and a single N-terminus, with initial yields of approximately 2
      pmol. Participants were asked to sequence 25 residues and return their results to
      the ESRG for analysis along with two completed surveys and an area/pmol table for
      repetitive and initial yield calculations. Data for 46 responses are presented
      which include initial yields, repetitive yields, sequencer performance, and
      ability to identify the protein.

PMID- 14715887
TI  - Optimizing the MALDI-TOF-MS observation of peptides containing disulfide bonds.
AB  - The observation of peaks corresponding to both disulfide-bonded and reduced
      peptides in matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectra of disulfides could suggest that the samples are either
      mixtures prior to analysis or that the measurement process has converted single
      compounds into mixtures. This is an important distinction when characterizing
      potentially disulfide-bonded peptides obtained from proteolyzed proteins or from
      oxidized synthetic peptides. It is well documented that disulfides can undergo in
      source decay (ISD) when using a 337-nm laser. However, the mixed matrix 2-(4
      hydroxyphenylazo)benzoic acid:alpha-cyano-4-hydroxycinnamic acid (1:10) not only
      suppresses the ISD reduction of disulfides to thiols but allows the same low
      threshold laser power generally used with alpha-cyano-4-hydroxycinnamic acid to
      be applied.

PMID- 14715888
TI  - Improvement in the detection of low concentration protein digests on a MALDI
      TOF/TOF workstation by reducing alpha-cyano-4-hydroxycinnamic acid adduct ions.
AB  - Alpha-cyano-4-hydroxycinnamic acid (alpha-CHCA) as a matrix facilitates the
      ionization of proteins and peptides in a matrix-assisted laser
      desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer. The matrix
      itself also ionizes and so do its sodium and potassium adducts. Matrix clusters
      and metal ion adducts interfere with peptide ionization and peptide mass spectrum
      interpretation. These matrix adducts are significantly reduced with addition of
      ammonium monobasic phosphate or ammonium dibasic citrate to the matrix and sample
      deposited onto the MALDI target. The reduction of matrix adducts results in the
      increase of peptide intensity and signal-to-noise ratio as well as in improvement
      of peptide ionization for samples deposited onto the target at levels of 10 fmol
      or below. These improvements were particularly significant in the detection of
      peptides at amol levels when reduced amounts of matrix were also used.

PMID- 14715889
TI  - TORquing toxins. Extra doses of movement-disorder protein guard neurons against
      poisons.

PMID- 14715890
TI  - Picky eater. Gluttonous cellular recycler hungers for damaged proteins.

PMID- 14715891
TI  - Weak of body, weak of mind? Dwindling testosterone concentrations in elderly men
      increase risk of Alzheimer's disease.

PMID- 14715892
TI  - Tasting longevity. Worms live longer after losing neurons for smell and taste.

PMID- 14715893
TI  - UnSIRtainty principle. Conflicting results underscore questions about how calorie
      restriction activates yeast longevity enzyme.

PMID- 14715894
TI  - There's a problem in the furnace.
AB  - A long-sought-after mutation in the manganese superoxide dismutase gene MnSOD has
      been isolated in Drosophila melanogaster. The MnSOD null mutation is recessive
      lethal, with death occurring just after eclosion. In this Perspective, I discuss
      these results and related work in mice within the context of the oxidative damage
      theory of aging.

PMID- 14715895
TI  - Maintaining your immune system--one method for enhanced longevity.
AB  - The immune system is an important evolutionary invention to battle invaders in
      young and old organisms. Successful aging in humans who achieve nonagenarian
      status and beyond depends on how the immune system changes over time. Whether
      certain immune parameters vary with increased age is influenced by the genotype
      and lifestyle of the individual.

PMID- 14715896
TI  - Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited
      desmin null cardiomyopathy.
AB  - One of the hallmarks of cardiomyopathy and heart failure is pronounced and
      progressive cardiomyocyte death. Understanding the mechanisms involved in
      cardiomyocyte cell death is a topic of great interest for treatment of cardiac
      disease. Mice null for desmin, the muscle-specific member of the intermediate
      filament gene family, develop cardiomyopathy characterized by extensive
      cardiomyocyte death, fibrosis, calcification, and eventual heart failure. The
      earliest ultrastructural defects are observed in mitochondria. In the present
      study, we have demonstrated that these mitochondrial abnormalities are the
      primary cause of the observed cardiomyopathy and that these defects can be
      ameliorated by overexpression of bcl-2 in desmin null heart. Overexpression of
      bcl-2 in the desmin null heart results in correction of mitochondrial defects,
      reduced occurrence of fibrotic lesions in the myocardium, prevention of cardiac
      hypertrophy, restoration of cardiomyocyte ultrastructure, and significant
      improvement of cardiac function. Furthermore, we have found that loss of desmin
      also diminishes the capacity of mitochondria to resist exposure to calcium, a
      defect that can be partially restored by bcl-2 overexpression. These results
      point to a unique function for desmin in protection of mitochondria from calcium
      exposure that can be partially rescued by overexpression of bcl-2. We show that
      bcl-2 cardiac overexpression has provided significant improvement of an inherited
      form of cardiomyopathy, revealing the potential for bcl-2, and perhaps other
      genes in the family, as therapeutic agents for heart disease of many types,
      including inherited forms.

PMID- 14715897
TI  - The HcrVf2 gene from a wild apple confers scab resistance to a transgenic
      cultivated variety.
AB  - The Vf gene from the wild species Malus floribunda 821 is the most studied apple
      scab resistance gene. Several molecular markers mapping around this gene were the
      starting point for a positional cloning project. The analysis of the bacterial
      artificial chromosome clones spanning the Vf region led to the identification of
      a cluster of genes homologous to the Cladosporium fulvum resistance gene family
      of tomato. One of these genes, HcrVf2 (homologue of the C. fulvum resistance
      genes of the Vf region), was used to transform the susceptible apple cultivar
      Gala. Four independent transformed lines resistant to apple scab were produced,
      proving that HcrVf2 is sufficient to confer scab resistance to a susceptible
      cultivar. The results show that direct gene transfer between cross-compatible
      species can be viable when, as in apple, the use of backcrosses to introduce
      resistance genes from wild species cannot exactly reconstitute the heterozygous
      genotype of clonally propagated cultivars.

PMID- 14715898
TI  - High-resolution molecular structure of a peptide in an amyloid fibril determined
      by magic angle spinning NMR spectroscopy.
AB  - Amyloid fibrils are self-assembled filamentous structures associated with protein
      deposition conditions including Alzheimer's disease and the transmissible
      spongiform encephalopathies. Despite the immense medical importance of amyloid
      fibrils, no atomic-resolution structures are available for these materials,
      because the intact fibrils are insoluble and do not form diffraction-quality 3D
      crystals. Here we report the high-resolution structure of a peptide fragment of
      the amyloidogenic protein transthyretin, TTR(105-115), in its fibrillar form,
      determined by magic angle spinning NMR spectroscopy. The structure resolves not
      only the backbone fold but also the precise conformation of the side chains.
      Nearly complete (13)C and (15)N resonance assignments for TTR(105-115) formed the
      basis for the extraction of a set of distance and dihedral angle restraints. A
      total of 76 self-consistent experimental measurements, including 41 restraints on
      19 backbone dihedral angles and 35 (13)C-(15)N distances between 3 and 6 A were
      obtained from 2D and 3D NMR spectra recorded on three fibril samples uniformly
      (13)C, (15)N-labeled in consecutive stretches of four amino acids and used to
      calculate an ensemble of peptide structures. Our results indicate that TTR(105
      115) adopts an extended beta-strand conformation in the amyloid fibrils such that
      both the main- and side-chain torsion angles are close to their optimal values.
      Moreover, the structure of this peptide in the fibrillar form has a degree of
      long-range order that is generally associated only with crystalline materials.
      These findings provide an explanation of the unusual stability and characteristic
      properties of this form of polypeptide assembly.

PMID- 14715899
TI  - Multiple substrates of the Legionella pneumophila Dot/Icm system identified by
      interbacterial protein transfer.
AB  - Legionella pneumophila is an intracellular pathogen that multiplies in a
      specialized vacuole within host cells. Biogenesis of this vacuole requires the
      Dot/Icm type IV protein translocation system. By using a Cre/loxP-based protein
      translocation assay, we found that proteins translocated by the Dot/Icm complex
      across the host phagosomal membrane can also be transferred from one bacterial
      cell to another. The flexibility of this system allowed the identification of
      several families of proteins translocated by the Dot/Icm complex. When analyzed
      by immunofluorescence microscopy, a protein identified by this procedure, SidC,
      was shown to translocate across the phagosomal membranes to the cytoplasmic face
      of the L. pneumophila phagosome. The identification of large numbers of these
      substrates, and the fact that the absence of any one substrate rarely results in
      strong defects in intracellular growth, indicate that there is significant
      functional redundancy among the Dot/Icm translocation targets.

PMID- 14715900
TI  - Successful induction of immune tolerance to enzyme replacement therapy in canine
      mucopolysaccharidosis I.
AB  - Immune responses can interfere with the effective use of therapeutic proteins to
      treat genetic deficiencies and have been challenging to manage. To address this
      problem, we adapted and studied methods of immune tolerance used in canine organ
      transplantation research to soluble protein therapeutics. A tolerization regimen
      was developed that prevents a strong antibody response to the enzyme alpha-l
      iduronidase during enzyme replacement therapy of a canine model of the lysosomal
      storage disorder mucopolysaccharidosis I. The tolerizing regimen consists of a
      limited 60-day course of cyclosporin A and azathioprine combined with weekly i.v.
      infusions of low-dose recombinant human alpha-l-iduronidase. The canines
      tolerized with this regimen maintain a reduced immune response for up to 6 months
      despite weekly therapeutic doses of enzyme in the absence of immunosuppressive
      drugs. Successful tolerization depended on high plasma levels of cyclosporin A
      combined with azathioprine. In addition, the induction of tolerance may require
      mannose 6-phosphate receptor-mediated uptake because alpha-l-iduronidase and
      alpha-glucosidase induced tolerance with the drug regimen whereas ovalbumin and
      dephosphorylated alpha-l-iduronidase did not. This tolerization method should be
      applicable to the treatment of other lysosomal storage disorders and provides a
      strategy to consider for other nontoleragenic therapeutic proteins and autoimmune
      diseases.

PMID- 14715901
TI  - Mitochondrial DNA sequences reveal the photosynthetic relatives of Rafflesia, the
      world's largest flower.
AB  - All parasites are thought to have evolved from free-living ancestors. However,
      the ancestral conditions facilitating the shift to parasitism are unclear,
      particularly in plants because the phylogenetic position of many parasites is
      unknown. This is especially true for Rafflesia, an endophytic holoparasite that
      produces the largest flowers in the world and has defied confident phylogenetic
      placement since its discovery >180 years ago. Here we present results of a
      phylogenetic analysis of 95 species of seed plants designed to infer the position
      of Rafflesia in an evolutionary context using the mitochondrial gene matR (1,806
      aligned base pairs). Overall, the estimated phylogenetic tree is highly congruent
      with independent analyses and provides a strongly supported placement of
      Rafflesia with the order Malpighiales, which includes poinsettias, violets, and
      passionflowers. Furthermore, the phylogenetic placement of Mitrastema, another
      enigmatic, holoparasitic angiosperm with the order Ericales (which includes
      blueberries and persimmons), was obtained with these data. Although traditionally
      classified together, Rafflesia and Mitrastema are only distantly related,
      implying that their endoparasitic habits result from convergent evolution. Our
      results indicate that the previous significant difficulties associated with
      phylogenetic placement of holoparasitic plants may be overcome by using
      mitochondrial DNA so that a broader understanding of the origins and evolution of
      parasitism may emerge.

PMID- 14715902
TI  - The costs and benefits of library site licenses to academic journals.
AB  - Scientific publishing is rapidly shifting from a paper-based system to one of
      predominantly electronic distribution, in which universities purchase site
      licenses for online access to journal contents. Will these changes necessarily
      benefit the scientific community? By using basic microeconomics and elementary
      statistical theory, we address this question and find a surprising answer. If a
      journal is priced to maximize the publisher's profits, scholars on average are
      likely to be worse off when universities purchase site licenses than they would
      be if access were by individual subscriptions only. However, site licenses are
      not always disadvantageous. Journals issued by professional societies and
      university presses are often priced so as to maximize subscriptions while
      recovering average costs. When such journals are sustained by institutional site
      licenses, the net benefits to the scientific community are larger than if these
      journals are sold only by individual subscriptions.

PMID- 14715903
TI  - Evidence for polar positional information independent of cell division and
      nucleoid occlusion.
AB  - We present evidence that, in Escherichia coli, polar positional information is
      present at midcell independent of known cell division factors. In filamented
      cells, IcsA, which is normally polar, localizes at or near potential cell
      division sites. Because the cell pole is derived from the septum, the sites to
      which IcsA localizes in filaments correspond to future poles. IcsA localization
      to these sites is independent of FtsZ, MinCDE, septation, and nucleoid occlusion,
      indicating that positional information for the future pole is independent of cell
      division and chromosome positioning. Upon IcsA localization to these sites,
      septation is inhibited, suggesting that IcsA recognition of this polar positional
      information may influence cell division.

PMID- 14715904
TI  - A respiratory hemocyanin from an insect.
AB  - Insects possess an elaborate tracheal system that enables transport of gaseous
      oxygen from the atmosphere directly to the inner organs. Therefore, the presence
      of specialized oxygen-transport proteins in the circulatory system of insects has
      been considered generally unnecessary. Here, we show for the first time, to our
      knowledge, the presence of an ancestral and functional hemocyanin (Hc) in an
      insect. In the hemolymph of nymphs and adults of the stonefly Perla marginata, a
      hexameric Hc was identified, which consists of two distinct subunit types of 659
      and 655 amino acids. P. marginata Hc displays cooperative oxygen binding with a
      moderately high oxygen affinity [(half-saturation pressure, P(50) approximately 8
      torr (1 torr = 133 Pa)]. No evidence was found for the presence of Hcs in the
      more evolutionarily advanced holometabolan insects, suggesting that this type of
      respiratory protein was lost later in insect evolution. However, our results
      demonstrate that, in contrast to the accepted paradigm, certain basal insects
      have retained an ancestral blood-based mechanism of gas exchange.

PMID- 14715905
TI  - Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine
      disturbances.
AB  - The possibility that exposures to environmental agents are associated with
      reproductive disorders in human populations has generated much public interest
      recently. Phthalate esters are used most commonly as plasticizers in the food and
      construction industry, and di-(2-ethylhexyl) phthalate (DEHP) is the most
      abundant phthalate in the environment. Daily human exposure to DEHP in the U.S.
      is significant, and occupational and clinical exposures from DEHP-plasticized
      medical devices, e.g., blood bags, hemodialysis tubing, and nasogastric feeding
      tubes, increase body burden levels. We investigated the effects of chronic
      exposures to low environmentally relevant DEHP levels on testicular function. Our
      data show that prolonged exposures to this agent induced high levels of the
      gonadotropin luteinizing hormone and increased the serum concentrations of sex
      hormones [testosterone and 17beta-estradiol (E2)] by >50%. Increased
      proliferative activity in Leydig cells was evidenced by enhanced expression of
      cell cycle proteins, as determined by RT-PCR. The numbers of Leydig cells in the
      testis of DEHP-treated rats were 40-60% higher than in control rats, indicating
      induction of Leydig cell hyperplasia. DEHP-induced elevations in serum
      testosterone and E2 levels suggest the possibility of multiple crosstalks between
      androgen, estrogen, and steroid hormone receptors, whereas the presence of
      estrogen receptors in nonreproductive tissues, e.g., cardiovascular system and
      bones, implies that the increases in serum E2 levels have implications beyond
      reproduction, including systemic physiology. Analysis of the effects of phthalate
      exposures on gonadotropin and steroid hormone levels should form part of overall
      risk assessment in human populations.

PMID- 14715906
TI  - Rapid refinement of crystallographic protein construct definition employing
      enhanced hydrogen/deuterium exchange MS.
AB  - Crystallographic efforts often fail to produce suitably diffracting protein
      crystals. Unstructured regions of proteins play an important role in this problem
      and considerable advantage can be gained in removing them. We have developed a
      number of enhancements to amide hydrogen/high-throughput and high-resolution
      deuterium exchange MS (DXMS) technology that allow rapid identification of
      unstructured regions in proteins. To demonstrate the utility of this approach for
      improving crystallization success, DXMS analysis was attempted on 24 Thermotoga
      maritima proteins with varying crystallization and diffraction characteristics.
      Data acquisition and analysis for 21 of these proteins was completed in 2 weeks
      and resulted in the localization and prediction of several unstructured regions
      within the proteins. When compared with those targets of known structure, the
      DXMS method correctly localized even small regions of disorder. DXMS analysis was
      then correlated with the propensity of such targets to crystallize and was
      further used to define truncations that improved crystallization. Truncations
      that were defined solely on DXMS analysis demonstrated greatly improved
      crystallization and have been used for structure determination. This approach
      represents a rapid and generalized method that can be applied to structural
      genomics or other targets in a high-throughput manner.

PMID- 14715907
TI  - Germinal center-associated nuclear protein contributes to affinity maturation of
      B cell antigen receptor in T cell-dependent responses.
AB  - Acquired immunity depends on proliferation and differentiation of antigen (Ag)
      specific B cells in germinal centers (GCs) of lymphoid follicles in response to T
      cell-dependent Ags. Here, we studied the function of GC-associated nuclear
      protein that is selectively up-regulated in GC-B cells. B cell-specific ganp
      deficient mice were compromised in affinity maturation of hapten-specific
      antibodies against T cell-dependent Ags with retarded development of GCs. B cell
      numbers and development, serum Ig levels, mitogen-induced B cell proliferation in
      vitro, and responses to T cell-independent Ag were nearly normal; however, the
      mutant B cells showed a decrease in anti-CD40-induced proliferation and an
      increased susceptibility to B cell apoptosis in vitro and in vivo. B cell
      specific ganp-deficient mice showed a decreased frequency of variable-region
      somatic mutations, especially of the high-affinity type (W(33) --> L) in the
      V(H)186.2 region against nitrophenyl-chicken gamma globulin, whereas the class
      switching was normal. We conclude that GC-associated nuclear protein is necessary
      for generation or maintenance of B cells with high-affinity B cell Ag receptors
      during the maturation in GCs.

PMID- 14715908
TI  - Coregulator-dependent facilitation of chromatin occupancy by GATA-1.
AB  - Coregulator recruitment by DNA-bound factors results in chromatin modification
      and protein-protein interactions, which regulate transcription. However, the
      mechanism by which the Friend of GATA (FOG) coregulator mediates GATA factor
      dependent transcription is unknown. We showed previously that GATA-1 replaces
      GATA-2 at an upstream region of the GATA-2 locus, and that this GATA switch
      represses GATA-2. Genetic complementation analysis in FOG-1-null hematopoietic
      precursors revealed that FOG-1 is not required for establishment or maintenance
      of the active GATA-2 domain, but is critical for the GATA switch. Analysis of
      GATA factor binding to additional loci also revealed FOG-1-dependent GATA
      switches. Thus, FOG-1 facilitates chromatin occupancy by GATA-1 at sites bound by
      GATA-2. We propose that FOG-1 is a prototype of a new class of coregulators
      termed chromatin occupancy facilitators, which confer coregulation in certain
      contexts via enhancing trans-acting factor binding to chromatin in vivo.

PMID- 14715909
TI  - Functional diversity of protein phosphatase-1, a cellular economizer and reset
      button.
AB  - The protein serine/threonine phosphatase protein phosphatase-1 (PP1) is a
      ubiquitous eukaryotic enzyme that regulates a variety of cellular processes
      through the dephosphorylation of dozens of substrates. This multifunctionality of
      PP1 relies on its association with a host of function-specific targetting and
      substrate-specifying proteins. In this review we discuss how PP1 affects the
      biochemistry and physiology of eukaryotic cells. The picture of PP1 that emerges
      from this analysis is that of a "green" enzyme that promotes the rational use of
      energy, the recycling of protein factors, and a reversal of the cell to a basal
      and/or energy-conserving state. Thus PP1 promotes a shift to the more energy
      efficient fuels when nutrients are abundant and stimulates the storage of energy
      in the form of glycogen. PP1 also enables the relaxation of actomyosin fibers,
      the return to basal patterns of protein synthesis, and the recycling of
      transcription and splicing factors. In addition, PP1 plays a key role in the
      recovery from stress but promotes apoptosis when cells are damaged beyond repair.
      Furthermore, PP1 downregulates ion pumps and transporters in various tissues and
      ion channels that are involved in the excitation of neurons. Finally, PP1
      promotes the exit from mitosis and maintains cells in the G1 or G2 phases of the
      cell cycle.

PMID- 14715910
TI  - Conus venoms: a rich source of novel ion channel-targeted peptides.
AB  - The cone snails (genus Conus) are venomous marine molluscs that use small,
      structured peptide toxins (conotoxins) for prey capture, defense, and competitor
      deterrence. Each of the 500 Conus can express approximately 100 different
      conotoxins, with little overlap between species. An overwhelming majority of
      these peptides are probably targeted selectively to a specific ion channel.
      Because conotoxins discriminate between closely related subtypes of ion channels,
      they are widely used as pharmacological agents in ion channel research, and
      several have direct diagnostic and therapeutic potential. Large conotoxin
      families can comprise hundreds or thousands of different peptides; most families
      have a corresponding ion channel family target (i.e., omega-conotoxins and Ca
      channels, alpha-conotoxins and nicotinic receptors). Different conotoxin families
      may have different ligand binding sites on the same ion channel target (i.e., mu
      conotoxins and delta-conotoxins to sites 1 and 6 of Na channels, respectively).
      The individual peptides in a conotoxin family are typically each selectively
      targeted to a diverse set of different molecular isoforms within the same ion
      channel family. This review focuses on the targeting specificity of conotoxins
      and their differential binding to different states of an ion channel.

PMID- 14715911
TI  - Structural contributions to short-term synaptic plasticity.
AB  - Synaptic ultrastructure is critical to many basic hypotheses about synaptic
      transmission. Various aspects of synaptic ultrastructure have also been
      implicated in the mechanisms of short-term plasticity. These forms of plasticity
      can greatly affect synaptic strength during ongoing activity. We review the
      evidence for how synaptic ultrastructure may contribute to facilitation,
      depletion, saturation, and desensitization.

PMID- 14715912
TI  - Long-term potentiation and memory.
AB  - One of the most significant challenges in neuroscience is to identify the
      cellular and molecular processes that underlie learning and memory formation. The
      past decade has seen remarkable progress in understanding changes that accompany
      certain forms of acquisition and recall, particularly those forms which require
      activation of afferent pathways in the hippocampus. This progress can be
      attributed to a number of factors including well-characterized animal models,
      well-defined probes for analysis of cell signaling events and changes in gene
      transcription, and technology which has allowed gene knockout and overexpression
      in cells and animals. Of the several animal models used in identifying the
      changes which accompany plasticity in synaptic connections, long-term
      potentiation (LTP) has received most attention, and although it is not yet clear
      whether the changes that underlie maintenance of LTP also underlie memory
      consolidation, significant advances have been made in understanding cell
      signaling events that contribute to this form of synaptic plasticity. In this
      review, emphasis is focused on analysis of changes that occur after learning,
      especially spatial learning, and LTP and the value of assessing these changes in
      parallel is discussed. The effect of different stressors on spatial
      learning/memory and LTP is emphasized, and the review concludes with a brief
      analysis of the contribution of studies, in which transgenic animals were used,
      to the literature on memory/learning and LTP.

PMID- 14715913
TI  - Localized effects of cAMP mediated by distinct routes of protein kinase A.
AB  - More than 20% of the human genome encodes proteins involved in transmembrane and
      intracellular signaling pathways. The cAMP-protein kinase A (PKA) pathway is one
      of the most common and versatile signal pathways in eukaryotic cells and is
      involved in regulation of cellular functions in almost all tissues in mammals.
      Various extracellular signals converge on this signal pathway through ligand
      binding to G protein-coupled receptors, and the cAMP-PKA pathway is therefore
      tightly regulated at several levels to maintain specificity in the multitude of
      signal inputs. Ligand-induced changes in cAMP concentration vary in duration,
      amplitude, and extension into the cell, and cAMP microdomains are shaped by
      adenylyl cyclases that form cAMP as well as phosphodiesterases that degrade cAMP.
      Different PKA isozymes with distinct biochemical properties and cell-specific
      expression contribute to cell and organ specificity. A kinase anchoring proteins
      (AKAPs) target PKA to specific substrates and distinct subcellular compartments
      providing spatial and temporal specificity for mediation of biological effects
      channeled through the cAMP-PKA pathway. AKAPs also serve as scaffolding proteins
      that assemble PKA together with signal terminators such as phosphatases and cAMP
      specific phosphodiesterases as well as components of other signaling pathways
      into multiprotein signaling complexes that serve as crossroads for different
      paths of cell signaling. Targeting of PKA and integration of a wide repertoire of
      proteins involved in signal transduction into complex signal networks further
      increase the specificity required for the precise regulation of numerous cellular
      and physiological processes.

PMID- 14715914
TI  - Neuroendocrine control of body fluid metabolism.
AB  - Mammals control the volume and osmolality of their body fluids from stimuli that
      arise from both the intracellular and extracellular fluid compartments. These
      stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and
      volume or pressure receptors. This information is conveyed to specific areas of
      the central nervous system responsible for an integrated response, which depends
      on the integrity of the anteroventral region of the third ventricle, e.g.,
      organum vasculosum of the lamina terminalis, median preoptic nucleus, and
      subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental
      role in the maintenance of body fluid homeostasis by secreting vasopressin and
      oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of
      the atrial natriuretic peptide (ANP), a large number of publications have
      demonstrated that this peptide provides a potent defense mechanism against volume
      overload in mammals, including humans. ANP is mostly localized in the heart, but
      ANP and its receptor are also found in hypothalamic and brain stem areas involved
      in body fluid volume and blood pressure regulation. Blood volume expansion acts
      not only directly on the heart, by stretch of atrial myocytes to increase the
      release of ANP, but also on the brain ANPergic neurons through afferent inputs
      from baroreceptors. Angiotensin II also plays an important role in the regulation
      of body fluids, being a potent inducer of thirst and, in general, antagonizes the
      actions of ANP. This review emphasizes the role played by brain ANP and its
      interaction with neurohypophysial hormones in the control of body fluid
      homeostasis.

PMID- 14715915
TI  - Cellular and molecular regulation of muscle regeneration.
AB  - Under normal circumstances, mammalian adult skeletal muscle is a stable tissue
      with very little turnover of nuclei. However, upon injury, skeletal muscle has
      the remarkable ability to initiate a rapid and extensive repair process
      preventing the loss of muscle mass. Skeletal muscle repair is a highly
      synchronized process involving the activation of various cellular responses. The
      initial phase of muscle repair is characterized by necrosis of the damaged tissue
      and activation of an inflammatory response. This phase is rapidly followed by
      activation of myogenic cells to proliferate, differentiate, and fuse leading to
      new myofiber formation and reconstitution of a functional contractile apparatus.
      Activation of adult muscle satellite cells is a key element in this process.
      Muscle satellite cell activation resembles embryonic myogenesis in several ways
      including the de novo induction of the myogenic regulatory factors. Signaling
      factors released during the regenerating process have been identified, but their
      functions remain to be fully defined. In addition, recent evidence supports the
      possible contribution of adult stem cells in the muscle regeneration process. In
      particular, bone marrow-derived and muscle-derived stem cells contribute to new
      myofiber formation and to the satellite cell pool after injury.

PMID- 14715916
TI  - Hyperinsulinism in infancy: from basic science to clinical disease.
AB  - Ion channelopathies have now been described in many well-characterized cell types
      including neurons, myocytes, epithelial cells, and endocrine cells. However, in
      only a few cases has the relationship between altered ion channel function, cell
      biology, and clinical disease been defined. Hyperinsulinism in infancy (HI) is a
      rare, potentially lethal condition of the newborn and early childhood. The causes
      of HI are varied and numerous, but in almost all cases they share a common target
      protein, the ATP-sensitive K+ channel. From gene defects in ion channel subunits
      to defects in beta-cell metabolism and anaplerosis, this review describes the
      relationship between pathogenesis and clinical medicine. Until recently, HI was
      generally considered an orphan disease, but as parallel defects in ion channels,
      enzymes, and metabolic pathways also give rise to diabetes and impaired insulin
      release, the HI paradigm has wider implications for more common disorders of the
      endocrine pancreas and the molecular physiology of ion transport.

PMID- 14715917
TI  - Brown adipose tissue: function and physiological significance.
AB  - The function of brown adipose tissue is to transfer energy from food into heat;
      physiologically, both the heat produced and the resulting decrease in metabolic
      efficiency can be of significance. Both the acute activity of the tissue, i.e.,
      the heat production, and the recruitment process in the tissue (that results in a
      higher thermogenic capacity) are under the control of norepinephrine released
      from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue
      is essential for classical nonshivering thermogenesis (this phenomenon does not
      exist in the absence of functional brown adipose tissue), as well as for the cold
      acclimation-recruited norepinephrine-induced thermogenesis. Heat production from
      brown adipose tissue is activated whenever the organism is in need of extra heat,
      e.g., postnatally, during entry into a febrile state, and during arousal from
      hibernation, and the rate of thermogenesis is centrally controlled via a pathway
      initiated in the hypothalamus. Feeding as such also results in activation of
      brown adipose tissue; a series of diets, apparently all characterized by being
      low in protein, result in a leptin-dependent recruitment of the tissue; this
      metaboloregulatory thermogenesis is also under hypothalamic control. When the
      tissue is active, high amounts of lipids and glucose are combusted in the tissue.
      The development of brown adipose tissue with its characteristic protein,
      uncoupling protein-1 (UCP1), was probably determinative for the evolutionary
      success of mammals, as its thermogenesis enhances neonatal survival and allows
      for active life even in cold surroundings.

PMID- 14715918
TI  - Pediatric research--a look toward the future.

PMID- 14715919
TI  - Tobacco control in the wake of the 1998 master settlement agreement.

PMID- 14715920
TI  - Complementarity-directed RNA dimer-linkage promotes retroviral recombination in
      vivo.
AB  - Retroviral particles contain a dimeric RNA genome, which serves as template for
      the generation of double-stranded DNA by reverse transcription. Transfer between
      RNA strands during DNA synthesis is governed by both sequence similarity between
      templates and structural features of the dimeric RNA. A kissing hairpin, believed
      to facilitate intermolecular recognition and dimer formation, was previously
      found to be a preferred site for recombination. To investigate if hairpin loop
      loop-complementarity is the primary determinant for this recombination
      preference, we have devised a novel 5' leader recombination assay based upon co
      packaging of two wild-type or loop-modified murine leukemia virus vector RNAs. We
      found that insertion of an alternative palindromic loop in one of the two vectors
      disrupted site-directed template switching, whereas site-specificity was restored
      between vectors with complementary non-wild-type palindromes. By pairing vector
      RNAs that contained identical non-palindromic loop motifs and that were unlikely
      to interact by loop-loop kissing, we found no preference for recombination at the
      kissing hairpin site. Of vector pairs designed to interact through base pairing
      of non-palindromic loop motifs, we could in one case restore hairpin-directed
      template switching, in spite of the reduced sequence identity, whereas another
      pair failed to support hairpin- directed recombination. However, analyses of in
      vitro RNA dimerization of all studied vector combinations showed a good
      correlation between efficient dimer formation between loop-modified viral RNAs
      and in vivo cDNA transfer at the kissing hairpin. Our findings demonstrate that
      complementarity between wild-type or non-wild-type hairpin kissing loops is
      essential but not sufficient for site-specific 5' leader recombination and lend
      further support to the hypothesis that a specific 'kissing' loop-loop interaction
      is guided by complementary sequences and maintained within the mature dimeric RNA
      of retroviruses.

PMID- 14715922
TI  - Hydration of short DNA, RNA and 2'-OMe oligonucleotides determined by osmotic
      stressing.
AB  - Studies on hydration are important for better understanding of structure and
      function of nucleic acids. We compared the hydration of self-complementary DNA,
      RNA and 2'-O-methyl (2'-OMe) oligonucleotides GCGAAUUCGC, (UA)6 and (CG)3 using
      the osmotic stressing method. The number of water molecules released upon melting
      of oligonucleotide duplexes, Delta(n)W, was calculated from the dependence of
      melting temperature on water activity and the enthalpy, both measured with UV
      thermal melting experiments. The water activity was changed by addition of
      ethylene glycol, glycerol and acetamide as small organic co-solutes. The
      Delta(n)W was 3-4 for RNA duplexes and 2-3 for DNA and 2'-OMe duplexes. Thus, the
      RNA duplexes were hydrated more than the DNA and the 2'-OMe oligonucleotide
      duplexes by approximately one to two water molecules depending on the sequence.
      Consistent with previous studies, GC base pairs were hydrated more than AU pairs
      in RNA, whereas in DNA and 2'-OMe oligonucleotides the difference in hydration
      between these two base pairs was relatively small. Our data suggest that the
      better hydration of RNA contributes to the increased enthalpic stability of RNA
      duplexes compared with DNA duplexes.

PMID- 14715921
TI  - Decoding the genome: a modified view.
AB  - Transfer RNA's role in decoding the genome is critical to the accuracy and
      efficiency of protein synthesis. Though modified nucleosides were identified in
      RNA 50 years ago, only recently has their importance to tRNA's ability to decode
      cognate and wobble codons become apparent. RNA modifications are ubiquitous. To
      date, some 100 different posttranslational modifications have been identified.
      Modifications of tRNA are the most extensively investigated; however, many other
      RNAs have modified nucleosides. The modifications that occur at the first, or
      wobble position, of tRNA's anticodon and those 3'-adjacent to the anticodon are
      of particular interest. The tRNAs most affected by individual and combinations of
      modifications respond to codons in mixed codon boxes where distinction of the
      third codon base is important for discriminating between the correct cognate or
      wobble codons and the incorrect near-cognate codons (e.g. AAA/G for lysine versus
      AAU/C asparagine). In contrast, other modifications expand wobble codon
      recognition, such as U*U base pairing, for tRNAs that respond to multiple codons
      of a 4-fold degenerate codon box (e.g. GUU/A/C/G for valine). Whether restricting
      codon recognition, expanding wobble, enabling translocation, or maintaining the
      messenger RNA, reading frame modifications appear to reduce anticodon loop
      dynamics to that accepted by the ribosome. Therefore, we suggest that anticodon
      stem and loop domain nucleoside modifications allow a limited number of tRNAs to
      accurately and efficiently decode the 61 amino acid codons by selectively
      restricting some anticodon-codon interactions and expanding others.

PMID- 14715923
TI  - Drosophila RNase Z processes mitochondrial and nuclear pre-tRNA 3' ends in vivo.
AB  - Although correct tRNA 3' ends are crucial for protein biosynthesis, generation of
      mature tRNA 3' ends in eukaryotes is poorly understood and has so far only been
      investigated in vitro. We report here for the first time that eukaryotic tRNA 3'
      end maturation is catalysed by the endonuclease RNase Z in vivo. Silencing of the
      JhI-1 gene (RNase Z homolog) in vivo with RNAi in Drosophila S2 cultured cells
      causes accumulation of nuclear and mitochondrial pre-tRNAs, suggesting that JhI-1
      encodes both forms of the tRNA 3' endonuclease RNase Z, and establishing its
      biological role in endonucleolytic tRNA 3' end processing. In addition our data
      show that in vivo 5' processing of nuclear and mitochondrial pre-tRNAs occurs
      before 3' processing.

PMID- 14715925
TI  - The nature of actinomycin D binding to d(AACCAXYG) sequence motifs.
AB  - Earlier studies by others had indicated that actinomycin D (ACTD) binds well to
      d(AACCATAG) and the end sequence TAG-3' is essential for its strong binding. In
      an effort to verify these assertions and to uncover other possible strong ACTD
      binding sequences as well as to elucidate the nature of their binding, systematic
      studies have been carried out with oligomers of d(AACCAXYG) sequence motifs,
      where X and Y can be any DNA base. The results indicate that in addition to TAG
      3', oligomers ending with XAG-3' and XCG-3' all provide binding constants > or =1
      x 10(7) M(-1) and even sequences ending with XTG-3' and XGG-3' exhibit binding
      affinities in the range 1-8 x 10(6) M(-1). The nature of the strong ACTD affinity
      of the sequences d(A1A2C3C4A5X6Y7G8) was delineated via comparative binding
      studies of d(AACCAAAG), d(AGCCAAAG) and their base substituted derivatives. Two
      binding modes are proposed to coexist, with the major component consisting of the
      3'-terminus G base folding back to base pair with C4 and the ACTD inserting at
      A2C3C4 by looping out the C3 while both faces of the chromophore are stacked by A
      and G bases, respectively. The minor mode is for the G to base pair with C3 and
      to have the same A/chromophore/G stacking but without a looped out base. These
      assertions are supported by induced circular dichroic and fluorescence spectral
      measurements.

PMID- 14715924
TI  - Enhanced mutagenic potential of 8-oxo-7,8-dihydroguanine when present within a
      clustered DNA damage site.
AB  - The formation of clustered DNA damage sites is a unique feature of ionizing
      radiation. Recent studies have shown that the repair of lesions within clusters
      may be compromised, but little is understood about the mutagenic consequences of
      such damage sites. Using a plasmid-based method, damaged DNA containing uracil
      positioned at 1-5 bp separations from 8-oxo-7,8-dihydroguanine on the
      complementary strand was transfected into wild-type Escherichia coli or into
      strains lacking the DNA glycosylases Fpg and MutY. Mutation frequencies were
      found to be significantly higher for clustered damage sites than for single
      lesions. The loss of MutY gave a large relative increase in mutation frequency
      and a strain lacking both Fpg and MutY showed even higher mutation frequencies,
      up to nearly 40% of rescued plasmid. In these strains, the mutation frequency
      decreases with increasing spacing of the uracil from the 8-oxo-7,8-dihydroguanine
      site. Sequencing of plasmid DNA carrying clustered damage, following rescue from
      bacteria, showed that almost all of the mutations are GC-->TA transversions. The
      data suggest that at clustered damage sites, depending on lesion spacing, the
      action of Fpg is compromised and post-replication processing of lesions by MutY
      is the most important mechanism for protection against mutagenesis.

PMID- 14715926
TI  - Detection of guanine-adenine mismatches by surface plasmon resonance sensor
      carrying naphthyridine-azaquinolone hybrid on the surface.
AB  - We have discovered a new molecule naphthyridine-azaquinolone hybrid (Npt-Azq)
      that strongly stabilized the guanine-adenine (G-A) mismatch in duplex DNA. In the
      presence of Npt-Azq, the melting temperature (T(m)) of 5'-d(CTA ACG GAA TG)-3'/3'
      d(GAT TGA CTT AC)-5' containing a single G-A mismatch increased by 15.4 degrees
      C, whereas fully matched duplex increased its T(m) only by 2.2 degrees C. Npt-Azq
      was immobilized on the sensor surface for the surface plasmon resonance (SPR)
      assay to examine SPR detection of duplexes containing a G-A mismatch. Distinct
      SPR signals were observed when 27mer DNA containing a G-A mismatch was analyzed
      by the Npt-Azq immobilized sensor surfaces, whereas the signal of the fully
      matched duplex was approximately 6-fold weaker in intensity. The SPR signals for
      the G-A mismatch were proportional to the concentration of DNA in a range up to 1
      microM, confirming that the SPR signal is in fact due to the binding of the G-A
      mismatch to Npt-Azq immobilized on the surface. Examination of all 16 G-A
      mismatches regarding the flanking sequence revealed that the sensor surface
      reported here is applicable to eight flanking sequences, covering 50% of all
      possible G-A mismatches.

PMID- 14715927
TI  - Characterization of cytosine methylated regions and 5-cytosine DNA
      methyltransferase (Ehmeth) in the protozoan parasite Entamoeba histolytica.
AB  - The DNA methylation status of the protozoan parasite Entamoeba histolytica was
      heretofore unknown. In the present study, we developed a new technique, based on
      the affinity of methylated DNA to 5-methylcytosine antibodies, to identify
      methylated DNA in this parasite. Ribosomal DNA and ribosomal DNA circles were
      isolated by this method and we confirmed the validity of our approach by sodium
      bisulfite sequencing. We also report the identification and the characterization
      of a gene, Ehmeth, encoding a DNA methyltransferase strongly homologous to the
      human DNA methyltransferase 2 (Dnmt2). Immunofluorescence microscopy using an
      antibody raised against a recombinant Ehmeth showed that Ehmeth is concentrated
      in the nuclei of trophozoites. The recombinant Ehmeth has a weak but significant
      methyltransferase activity when E.histolytica genomic DNA is used as substrate. 5
      Azacytidine (5-AzaC), an inhibitor of DNA methyltransferase, was used to study in
      vivo the role of DNA methylation in E.histolytica. Genomic DNA of trophozoites
      grown with 5-AzaC (23 microM) was undermethylated and the ability of 5-AzaC
      treated trophozoites to kill mammalian cells or to cause liver abscess in
      hamsters was strongly impaired.

PMID- 14715928
TI  - Biological effects of the dual phenotypic Janus mutation of ret cosegregating
      with both multiple endocrine neoplasia type 2 and Hirschsprung's disease.
AB  - Gain-of-function mutations of ret receptor tyrosine kinase, the signaling
      receptor for glial cell line-derived neurotrophic factor, cause sporadic thyroid
      and adrenal malignancies as well as endocrine cancer syndromes, such as multiple
      endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary
      thyroid carcinoma. Loss-of-function mutations of ret cause Hirschsprung's disease
      (HSCR) or colonic aganglionosis. In 20-30% of families with a mutation at
      residues 609, 611, 618, or 620 of RET, MEN 2A and familial medullary thyroid
      carcinoma cosegregate with HSCR. These mutations constitutively activate RET due
      to aberrant disulfide homodimerization and diminish the level of RET at the
      plasma membrane. It is not known how these mutations simultaneously lead to both
      gain- and loss-of-function RET-associated diseases. We provide an explanation for
      the dual phenotypic Janus mutation at Cys620 of RET. In Madin-Darby canine kidney
      (MDCK) cells, the Janus mutation impairs the glial cell line-derived neurotrophic
      factor-induced effects of RET on cell migration, differentiation, and survival
      but simultaneously promotes rapid cell proliferation.

PMID- 14715929
TI  - A response unit in the first exon of the beta-amyloid precursor protein gene
      containing thyroid hormone receptor and Sp1 binding sites mediates negative
      regulation by 3,5,3'-triiodothyronine.
AB  - Thyroid hormones repress expression of APP (beta-amyloid precursor protein) in
      cultured cells of neuronal origin. The effect involves binding to the nuclear
      thyroid hormone receptor (TR) and is mediated by DNA sequences located within the
      first exon of the gene. These sequences contain a thyroid hormone response
      element that is necessary, but not sufficient, to mediate the inhibitory effect
      of the thyroid hormone T(3). In this report, we show that repression by T(3) is
      mediated by a response unit composed by the thyroid hormone response element and
      5'-flanking sequences that bind Sp1 and mediate stimulation by this transcription
      factor. In that unit, binding sites for TR and Sp1 overlap and a complex
      mechanism appears to account for the TR-mediated regulation of APP. Unliganded TR
      does not bind to DNA and allows Sp1 to bind to DNA and stimulate APP basal
      expression. Binding of ligand T(3), which increases affinity of TR by DNA,
      precludes binding of Sp1 to DNA and decreases the Sp1-dependent expression of
      APP.

PMID- 14715930
TI  - Identification of a liver-specific uridine phosphorylase that is regulated by
      multiple lipid-sensing nuclear receptors.
AB  - In this work, we report the characterization of a novel liver-specific gene (L
      UrdPase), whose expression is regulated by a number of hepatic nuclear receptors
      (including liver X receptors, peroxisome proliferator-activated receptor alpha,
      farnesoid X receptor, and hepatic nuclear factor-4alpha), which have been shown
      to be involved in lipid metabolism. L-UrdPase encodes a previously
      uncharacterized protein with similarity to an intestine-specific uridine
      phosphorylase. Enzymatic assays confirmed that L-UrdPase has uridine
      phosphorylase activity. However, L-UrdPase has a highly restricted,
      nonoverlapping pattern of expression with its intestinal counterpart and is
      regulated in a distinct manner by several different nuclear receptors. The
      identification of the liver uridine phosphorylase and its characterization as a
      target of lipid-sensing nuclear receptors implies the existence of a previously
      unknown nuclear receptor signaling pathway that links lipid and uridine
      metabolism.

PMID- 14715931
TI  - Epigenetic modifications at the human growth hormone locus predict distinct roles
      for histone acetylation and methylation in placental gene activation.
AB  - Developmental control of eukaryotic gene expression is tightly linked to
      alterations in chromatin structure. Studies of the hGH multigene cluster suggest
      that the four placental genes are activated by a pathway of histone modification
      distinct from the pathway leading to activation of the single pituitary hGH-N
      gene. The relationship between histone acetylation and hGH-N activation in the
      pituitary has been previously defined using a combination of epigenetic mapping
      and transgenic analyses. The repeated gene structures within the hGH cluster had
      been an impediment to comparable analysis of placental gene activation. In the
      present report we defined patterns of core histone acetylation and methylation
      within and flanking the hGH cluster in human placental chromatin. These data
      highlight differences between placental and pituitary pathways of transcriptional
      control at the hGH cluster and suggest that selective activation of the placental
      genes reflects distinct roles for histone acetyltransferase and histone
      methyltransferase coactivator complexes.

PMID- 14715932
TI  - Production and release of neuroprotective tumor necrosis factor by P2X7 receptor
      activated microglia.
AB  - After a brain insult, ATP is released from injured cells and activates microglia.
      The microglia that are activated in this way then release a range of bioactive
      substances, one of which is tumor necrosis factor (TNF). The release of TNF
      appears to be dependent on the P2X7 receptor. The inhibitors 1,4-diamino-2,3
      dicyano-1,4-bis[2-amino-phenylthio]butadiene (U0126), anthra[1,9-cd]pyrazol-6(2H)
      one (SP600125), and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)IH
      imidazole (SB203580), which target MEK (mitogen-activated protein kinase kinase),
      JNK (c-Jun N-terminal kinase), and p38, respectively, all potently suppress the
      production of TNF in ATP-stimulated microglia, whereas the production of TNF mRNA
      is strongly inhibited by U0126 and SP600125. SB203580 did not affect the
      increased levels of TNF mRNA but did prevent TNF mRNA from accumulating in the
      cytoplasm. The ATP-provoked activation of JNK and p38 [but not extracellular
      signal-regulated kinase (ERK)] could be inhibited by brilliant blue G, a P2X7
      receptor blocker, and by genistein and 4-amino-5-(4-chlorophenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine, which are general and src-family-specific
      tyrosine kinase inhibitors, respectively. Most important, we found that treatment
      of the microglia in neuron-microglia cocultures with the P2X7 agonist 2'-3'-O
      (benzoyl-benzoyl) ATP led to significant reductions in glutamate-induced neuronal
      cell death, and that either TNF-alpha converting enzyme inhibitor or anti-TNF
      readily suppressed the protective effect implied by this result. Together, these
      findings indicate that both ERK and JNK are involved in the regulation of TNF
      mRNA expression, that p38 is involved in the nucleocytoplasmic transport of TNF
      mRNA, and that a PTK (protein tyrosine kinase), possibly a member of the src
      family, acts downstream of the P2X7 receptor to activate JNK and p38. Finally,
      our data suggest that P2X7 receptor-activated microglia protect neurons against
      glutamate toxicity primarily because they are able to release TNF.

PMID- 14715933
TI  - Dopamine D1/D5 receptor modulates state-dependent switching of soma-dendritic
      Ca2+ potentials via differential protein kinase A and C activation in rat
      prefrontal cortical neurons.
AB  - To determine the nature of dopamine modulation of dendritic Ca2+ signaling in
      layers V-VI prefrontal cortex (PFC) neurons, whole-cell Ca2+ potentials were
      evoked after blockade of Na+ and K+ channels. Soma-dendritic Ca2+ spikes evoked
      by suprathreshold depolarizing pulses, which could be terminated by superimposed
      brief intrasomatic hyperpolarizing pulses, are blocked by the L-type Ca2+ channel
      antagonist nimodipine (1 microM). The D1/D5 receptor agonist dihydrexidine (DHX)
      (0.01-10 microM; 5 min) or R-(+)SKF81291 (10 microM) induced a prolonged (>30
      min) dose-dependent peak suppression of these Ca2+ spikes. This effect was
      dependent on [Ca2+]i- and protein kinase C (PKC)-dependent mechanisms because
      [Ca2+]i chelation by BAPTA or inhibition of PKC by bisindolymaleimide (BiM1), but
      not inhibition of [Ca2+]i release with heparin or Xestospongin C, prevented the
      D1-mediated suppression of Ca2+ spikes. Depolarizing pulses subthreshold to
      activating a Ca2+ spike evoked a nimodipine-sensitive Ca2+ "hump" potential.
      D1/D5 stimulation induced an N-[2-((o-bromocinamyl)amino)ethyl]-5
      isoquinolinesulfonamide (H-89)- or internal PKA inhibitory peptide[5-24]
      sensitive (PKA-dependent) transient (approximately 7 min) potentiation of the
      hump potential to full Ca2+ spike firing. Furthermore, application of DHX in the
      presence of the PKC inhibitor BiM1 or internal PKC inhibitory peptide[19-36]
      resulted in persistent firing of full Ca2+ spike bursts, suggesting that a D1/D5
      PKA mechanism switches subthreshold Ca2+ hump potential to fire full Ca2+ spikes,
      which are eventually turned off by a D1/D5-Ca2+-dependent PKC mechanism. This
      depolarizing state-dependent, D1/D5-activated, bi-directional switching of soma
      dendritic L-type Ca2+ channels via PKA-dependent potentiation and PKC-dependent
      suppression may provide spatiotemporal regulation of synaptic integration and
      plasticity in PFC.

PMID- 14715934
TI  - Preterm fetal hypoxia-ischemia causes hypertonia and motor deficits in the
      neonatal rabbit: a model for human cerebral palsy?
AB  - Prenatal hypoxia-ischemia to the developing brain has been strongly implicated in
      the subsequent development of the hypertonic motor deficits of cerebral palsy
      (CP) in premature and full-term infants who present with neonatal encephalopathy.
      Despite the enormous impact of CP, there is no animal model that reproduces the
      hypertonia and motor disturbances of this disorder. We report a rabbit model of
      in utero placental insufficiency, in which hypertonia is accompanied by marked
      abnormalities in motor control. Preterm fetuses (67-70% gestation) were subjected
      to sustained global hypoxia. The dams survived and gave spontaneous birth. At
      postnatal day 1, the pups that survived were subjected to a battery of
      neurobehavioral tests developed specifically for these animals, and the tests
      were videotaped and scored in a masked manner. Newborn pups of hypoxic groups
      displayed significant impairment in multiple tests of spontaneous locomotion,
      reflex motor activity, and the coordination of suck and swallow. Increased tone
      of the limbs at rest and with active flexion and extension were observed in the
      survivors of the preterm insult. Histopathological studies identified a distinct
      pattern of acute injury to subcortical motor pathways that involved the basal
      ganglia and thalamus. Persistent injury to the caudate putamen and thalamus at P1
      was significantly correlated with hypertonic motor deficits in the hypoxic group.
      Antenatal hypoxia-ischemia at preterm gestation results in hypertonia and
      abnormalities in motor control. These findings provide a unique behavioral model
      to define mechanisms and sequelae of perinatal brain injury from antenatal
      hypoxia-ischemia.

PMID- 14715935
TI  - Production of resurgent current in NaV1.6-null Purkinje neurons by slowing sodium
      channel inactivation with beta-pompilidotoxin.
AB  - Voltage-gated tetrodotoxin-sensitive sodium channels of Purkinje neurons produce
      "resurgent" current with repolarization, which results from relief of an open
      channel block that terminates current flow at positive potentials. The associated
      recovery of sodium channels from inactivation is thought to facilitate the rapid
      firing patterns characteristic of Purkinje neurons. Resurgent current appears to
      depend primarily on NaV1.6 alpha subunits, because it is greatly reduced in "med"
      mutant mice that lack NaV1.6. To identify factors that regulate the
      susceptibility of alpha subunits to open-channel block, we voltage clamped wild
      type and med Purkinje neurons before and after slowing conventional inactivation
      with beta-pompilidotoxin (beta-PMTX). beta-PMTX increased resurgent current in
      wild-type neurons and induced resurgent current in med neurons. In med cells, the
      resurgent component of beta-PMTX-modified sodium currents could be selectively
      abolished by application of intracellular alkaline phosphatase, suggesting that,
      like in NaV1.6-expressing cells, the open-channel block of NaV1.1 and NaV1.2
      subunits is regulated by constitutive phosphorylation. These results indicate
      that the endogenous blocker exists independently of NaV1.6 expression, and
      conventional inactivation regulates resurgent current by controlling the extent
      of open-channel block. In Purkinje cells, therefore, the relatively slow
      conventional inactivation kinetics of NaV1.6 appear well adapted to carry
      resurgent current. Nevertheless, NaV1.6 is not unique in its susceptibility to
      open-channel block, because under appropriate conditions, the non-NaV1.6 subunits
      can produce robust resurgent currents.

PMID- 14715936
TI  - The secretory granule-associated protein CAPS2 regulates neurotrophin release and
      cell survival.
AB  - Neurotrophins are key modulators of various neuronal functions, including
      differentiation, survival, and synaptic plasticity, but the molecules that
      regulate their secretion are poorly understood. We isolated a clone that is
      predominantly expressed in granule cells of postnatally developing mouse
      cerebellum, which turned out to be a paralog of CAPS (Ca2+-dependent activator
      protein for secretion), and named CAPS2. CAPS2 is enriched on vesicular
      structures of presynaptic parallel fiber terminals of granule cells connecting
      postsynaptic spines of Purkinje cell dendrites. Vesicle factions affinity
      purified by the CAPS2 antibody from mouse cerebella contained significant amounts
      of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and
      chromogranin B but not marker proteins for synaptic vesicle synaptophysin and
      synaptotagmin. In cerebellar primary cultures, punctate CAPS2 immunoreactivities
      are primarily colocalized with those of NT-3 and BDNF and near those of a
      postsynaptic marker, postsynaptic density-95, around dendritic arborization of
      Purkinje cells. Exogenously expressed CAPS2 enhanced release of exogenous NT-3
      and BDNF from PC12 cells and endogenous NT-3 from cultured granule cells in a
      depolarization-dependent manner. Moreover, the overexpression of CAPS2 in granule
      cells promotes the survival of Purkinje cells in cerebellar cultures. Thus, we
      suggest that CAPS2 mediates the depolarization-dependent release of NT-3 and BDNF
      from granule cells, leading to regulation in cell differentiation and survival
      during cerebellar development.

PMID- 14715937
TI  - Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in
      rat ventral tegmental area dopamine neurons through activation of CB1 receptors.
AB  - The endogenous cannabinoid system has been shown to play a crucial role in
      controlling neuronal excitability and synaptic transmission. In this study we
      investigated the effects of a cannabinoid receptor (CB-R) agonist WIN 55,212-2
      (WIN) on excitatory synaptic transmission in the rat ventral tegmental area
      (VTA). Whole-cell patch clamp recordings were performed from VTA dopamine (DA)
      neurons in an in vitro slice preparation. WIN reduced both NMDA and AMPA EPSCs,
      as well as miniature EPSCs (mEPSCs), and increased the paired-pulse ratio,
      indicating a presynaptic locus of its action. We also found that WIN-induced
      effects were dose-dependent and mimicked by the CB1-R agonist HU210. Furthermore,
      two CB1-R antagonists, AM281 and SR141716A, blocked WIN-induced effects,
      suggesting that WIN modulates excitatory synaptic transmission via activation of
      CB1-Rs. Our additional finding that both AM281 and SR141716A per se increased
      NMDA EPSCs suggests that endogenous cannabinoids, released from depolarized
      postsynaptic neurons, might act retrogradely on presynaptic CB1-Rs to suppress
      glutamate release. Hence, we report that a type of synaptic modulation,
      previously termed depolarization-induced suppression of excitation (DSE), is
      present also in the VTA as a calcium-dependent phenomenon, blocked by both AM281
      and SR141716A, and occluded by WIN. Importantly, DSE was partially blocked by the
      D2DA antagonist eticlopride and enhanced by the D2DA agonist quinpirole without
      changing the presynaptic cannabinoid sensitivity. These results indicate that the
      two pathways work in a cooperative manner to release endocannabinoids in the VTA,
      where they play a role as retrograde messengers for DSE via CB1-Rs.

PMID- 14715938
TI  - Nicotinic enhancement of the noradrenergic inhibition of sleep-promoting neurons
      in the ventrolateral preoptic area.
AB  - According to multiple lines of evidence, neurons in the ventrolateral preoptic
      area (VLPO) that contain GABA promote sleep by inhibiting neurons of the arousal
      systems. Reciprocally, transmitters used by these systems, including
      acetylcholine (ACh) and noradrenaline (NA), exert an inhibitory action on the
      VLPO neurons. Because nicotine, an agonist of ACh, acts as a potent stimulant, we
      queried whether it might participate in the cholinergic inhibition of these sleep
      promoting cells. Indeed, we found that ACh inhibits the VLPO neurons through a
      nicotinic, as well as a muscarinic, action. As evident in the presence of
      atropine, the non-muscarinic component was mimicked by epibatidine, a
      nonselective nicotinic ACh receptor (nAChR) agonist and was blocked by dihydro
      beta-erythroidine, a nonselective nAChR antagonist. It was not, however, blocked
      by methyllycaconitine, a selective antagonist of the alpha7 subtype, indicating
      that the action was mediated by non-alpha7 nAChRs. The nicotinic inhibition was
      attributed to a presynaptic facilitation of NA release because it persisted in
      the presence of tetrodotoxin and was blocked by yohimbine and RS 79948, which are
      both selective antagonists of alpha2 adrenergic receptors. Sleep-promoting VLPO
      neurons are thus dually inhibited by ACh through a muscarinic postsynaptic action
      and a nicotinic presynaptic action on noradrenergic terminals. Such dual
      complementary actions allow ACh and nicotine to enhance wakefulness by inhibiting
      sleep-promoting systems while facilitating other wake-promoting systems.

PMID- 14715939
TI  - Phenotype matters: identification of light-responsive cells in the mouse
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus is the neural locus of the
      circadian clock. To explore the organization of the SCN, two strains of
      transgenic mice, each bearing a jellyfish green fluorescent protein (GFP)
      reporter, were used. In one, GFP was driven by the promoter region of the mouse
      Period1 gene (mPer1) (Per1::GFP mouse), whereas in the other, GFP was inserted in
      the promoter region of calbindin-D(28K)-bacterial artificial chromosome
      (CalB::GFP mouse). In the latter mouse, GFP-containing SCN cells are
      immunopositive for gastrin-releasing peptide. In both mouse lines, light-induced
      Per1 mRNA and Fos are localized to the SCN subregion containing gastrin-releasing
      peptide. Double-label immunohistochemistry reveals that most gastrin-releasing
      peptide cells (approximately 70%) contain Fos after a brief light pulse. To
      determine the properties of SCN cells in this light-responsive region, we
      examined the expression of rhythmic Period genes and proteins. Gastrin-releasing
      peptide-containing cells do not express detectable rhythms in these key
      components of the molecular circadian clock. The results support the view that
      the mammalian SCN is composed of functionally distinct cell groups, of which some
      are light induced and others are rhythmic with respect to clock gene expression.
      Furthermore, the findings suggest that gastrin-releasing peptide is a potential
      mediator of intercellular communication between light-induced and oscillator
      cells within the SCN.

PMID- 14715940
TI  - Extracellular signal-regulated kinase 1/2 is required for the induction of group
      I metabotropic glutamate receptor-mediated epileptiform discharges.
AB  - Transient stimulation of group I metabotropic glutamate receptors (mGluRs)
      induces persistent prolonged epileptiform discharges in hippocampal slices via a
      protein synthesis-dependent process. At present, the signaling process underlying
      the induction of these epileptiform discharges remains unknown. We examined the
      possible role of extracellular signal-regulated kinases (ERK1 and ERK2) because
      these kinases can be activated by group I mGluRs, and their activation may
      regulate gene expression and alter protein synthesis. The group I mGluR agonist
      (S)-3,5-dihydroxyphenylglycine (DHPG; 50 microm) induced activation of ERK1/2 in
      hippocampal slices. 2-(2-Diamino-3-methoxyphenyl-4H-1-benzopyran-4-one (PD98059)
      (50 microm) a specific inhibitor of mitogen-activated protein kinase kinase
      (MEK), suppressed ERK1/2 activation by DHPG. PD98059 or another MEK inhibitor,
      1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (10 microm), also
      prevented the induction of the prolonged epileptiform discharges by DHPG. In the
      presence of ionotropic glutamate receptor inhibitors and tetrodotoxin (blockers),
      DHPG-induced epileptiform discharges were suppressed, whereas ERK1/2 activation
      persisted. Protein kinase C inhibitors (2-[1-(3-dimethylaminopropyl)-5
      methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide, 1 microm; or chelerythrine, 10
      microm) did not prevent the generation of DHPG-induced epileptiform discharges,
      nor did they suppress the activation of ERK1/2 by DHPG in slices pretreated with
      the blockers. Genistein (30 microm), a broad-spectrum tyrosine kinase inhibitor,
      suppressed the DHPG-induced epileptiform discharges and the ERK1/2 activation in
      the presence of blockers. Induction of DHPG-mediated epileptiform discharges was
      also suppressed by 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      D]pyrimidine (10 microm), an Src-family tyrosine kinase inhibitor. The study
      shows that group I mGluRs activate ERK1/2 through a tyrosine kinase-dependent
      process and that this activation of ERK1/2 is necessary for the induction of
      prolonged epileptiform discharges in the hippocampus.

PMID- 14715941
TI  - Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse
      subventricular zone and olfactory bulb.
AB  - The subventricular zone of the rodent brain retains the capacity of generating
      new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward
      the olfactory bulb, where they differentiate as granular and periglomerular
      interneurons. The reported presence of differentiated neurons expressing the
      neuronal isoform of nitric oxide synthase (NOS) in the periphery of the
      neurogenic region and the organization of their varicose axons as a network in
      which the precursors are immersed raised the hypothesis that endogenous nitric
      oxide (NO) may participate in the control of neurogenesis in the subventricular
      zone. Systemic administration of the NOS inhibitors N(omega)-nitro-L-arginine
      methyl ester or 7-nitroindazole to adult mice produced a dose- and time-dependent
      increase in the number of mitotic cells in the subventricular zone, rostral
      migratory stream, and olfactory bulb, but not in the dentate gyrus of the
      hippocampus, without affecting apoptosis. In the subventricular zone, this effect
      was exerted selectively on a precursor subpopulation expressing nestin but not
      neuronal or glial cell-specific proteins. In addition, in the olfactory bulb,
      analysis of maturation markers in the newly generated neurons indicated that
      chronic NOS inhibition caused a delay in neuronal differentiation. Postmitotic
      cell survival and migration were not affected when NO production was impaired.
      Our results suggest that NO, produced by nitrergic neurons in the adult mouse
      subventricular zone and olfactory bulb, exerts a negative control on the size of
      the undifferentiated precursor pool and promotes neuronal differentiation.

PMID- 14715942
TI  - Tetraspanin protein CD9 is a novel paranodal component regulating paranodal
      junctional formation.
AB  - The axoglial paranodal junction is essential for the proper localization of ion
      channels around the node of Ranvier. The integrity of this junction is important
      for nerve conduction. Although recent studies have made significant progress in
      understanding the molecular composition of the paranodal junction, it is not
      known how these membrane components are distributed to the appropriate sites and
      interact with each other. Here we show that CD9, a member of the tetraspanin
      family, is present at the paranode. CD9 is concentrated in the paranode as
      myelination proceeds, but CD9 clusters become diffuse, associated with disruption
      of the paranode, in cerebroside sulfotransferase-deficient mice.
      Immunohistochemical and Western blot analysis showed that CD9 is distributed
      predominantly in the PNS. Ablation of CD9 in mutant mice disrupts junctional
      attachment at the paranode and alters the paranodal components contactin
      associated protein (also known as Paranodin) and neurofascin 155, although the
      frequency of such abnormalities varies among individuals and individual axons
      even in the same mouse. Electron micrographs demonstrated that compact myelin
      sheaths were also affected in the PNS. Therefore, CD9 is a myelin protein
      important for the formation of paranodal junctions. CD9 also plays a role in the
      formation of compact myelin in the PNS.

PMID- 14715943
TI  - Climbing fiber activation of EAAT4 transporters and kainate receptors in
      cerebellar Purkinje cells.
AB  - Cerebellar Purkinje cells (PCs) express two glutamate transporters, EAAC1 (EAAT3)
      and EAAT4; however, their relative contribution to the uptake of glutamate at
      synapses is not known. We found that glutamate transporter currents recorded at
      climbing fiber (CF)-PC synapses are absent in mice lacking EAAT4 but unchanged in
      mice lacking EAAC1, indicating that EAAT4 is preferentially involved in clearing
      glutamate from CF synapses. However, comparison of CF synaptic currents between
      wild-type and transporter knock-out mice revealed that ionotropic glutamate
      receptors are responsible for >40% of the current previously attributed to
      transporters, indicating that PCs remove <10% of the glutamate released by the
      CF. The receptors responsible for the nontransporter component accounted for 5%
      of the CF EPSC, had a slower time course and lower occupancy than AMPA receptors
      at CF synapses, and exhibited pharmacological properties consistent with kainate
      receptors. In GluR5 knock-out mice, this current was dramatically reduced,
      indicating that CF excitation of PCs involves two distinct classes of ionotropic
      glutamate receptors, AMPA receptors and GluR5-containing kainate receptors.

PMID- 14715944
TI  - Transient electrical coupling delays the onset of chemical neurotransmission at
      developing synapses.
AB  - The formation and subsequent elimination of electrical coupling between neurons
      has been demonstrated in many developing vertebrate and invertebrate nervous
      systems. The relationship between the disappearance of electrical synaptic
      connectivity and the appearance of chemical neurotransmission is not well
      understood. We report here that identified motoneurons from the snail Helisoma
      formed transient electrical and chemical connections during regeneration both in
      vivo and in vitro. Electrical connections that formed in vivo were strongest by
      day 2 and no longer detectable by day 7. During elimination of this electrical
      connection, an inhibitory chemical connection from 110 onto 19 formed. This
      sequence of synaptic development was recapitulated in cell culture with a similar
      time course. The relationship between the appearance of transient electrical
      coupling and its possible effects on the subsequent chemical synaptogenesis were
      examined by reducing transient intercellular coupling. Trophic factor-deprived
      medium resulted in a 66% reduction in coupling coefficient. In these conditions,
      the unidirectional chemical connection formed readily; in contrast, chemical
      synaptogenesis was delayed in cell pairs exposed to trophic factors where
      transient electrical coupling was strong. Dye coupling and synaptic vesicle
      cycling studies supported electrophysiological results. Exposure to cholinergic
      antagonists, curare and hexamethonium bromide, which block chemical
      neurotransmission in these synapses, resulted in prolonged maintenance of the
      electrical connection. These studies demonstrated an inverse relationship between
      chemical and electrical connectivity at early stages of synaptic development and
      suggest a dynamic interaction between these forms of neuronal communication as
      adult neural networks are constructed or regenerated.

PMID- 14715945
TI  - Wnt signaling mutants have decreased dentate granule cell production and radial
      glial scaffolding abnormalities.
AB  - LRP6 mutant mice have generalized defects in the Wnt/beta-catenin signaling
      pathway because of the crucial function of LRP6 as a Wnt signaling co-receptor
      (Pinson et al., 2000). We examined the hippocampal phenotype of single LRP6
      mutant mice as well as LRP6/Lef1 double mutant mice. LRP6 mutants had reduced
      production of dentate granule neurons and abnormalities of the radial glial
      scaffolding in the forming dentate gyrus. These defects were more severe with the
      addition of a single Lef1 null allele to an LRP6 null background. Pyramidal cell
      fields were unaffected in the LRP6, Lef1, or double mutants. The dentate defects
      were accompanied by decreased numbers of mitotic precursors in the migratory
      pathway to the dentate and in the displaced proliferative zone in the dentate
      itself. At earlier gestational ages, there was a reduction in the number of
      dentate granule cell progenitors in the dentate ventricular zone before the
      emigration of the earliest differentiated granule neurons and precursors to form
      the dentate anlage.

PMID- 14715946
TI  - Input-specific modulation of neurotransmitter release in the lateral horn of the
      spinal cord via adenosine receptors.
AB  - Activation of adenosine A2A receptors (A2ARs) in the CNS produces a variety of
      neuromodulatory actions dependent on the region and preparation examined. In
      autonomic regions of the spinal cord, A1R activation decreases excitatory
      synaptic transmission, but the effects of A2AR stimulation are unknown. We sought
      to determine the location and function of the A2ARs in the thoracic spinal cord,
      focusing on the intermediolateral cell column (IML). A2AR immunoreactivity was
      observed throughout the gray matter, with particularly dense immunostaining in
      regions containing sympathetic preganglionic neurons (SPNs), namely, the IML and
      intercalated nucleus. Electron microscopy revealed A2AR immunoreactivity within
      presynaptic terminals and in postsynaptic structures in the IML. To study the
      functional relevance of these A2ARs, visualized whole-cell patch-clamp recordings
      were made from electrophysiologically identified SPNs and interneurons within the
      IML. The A2AR agonist c2-[p-(carboxyethyl)phenethylamino]-5'-N
      ethylcarboxyamidoadenosine (CGS 21680) had no significant effect on EPSPs but
      increased the amplitude of IPSPs elicited by stimulation of the lateral
      funiculus. These effects were attributable to activation of presynaptic A2ARs
      because CGS 21680 application altered the paired pulse ratio. Furthermore,
      neurons in the IML that have IPSPs increased via A2AR activation also receive
      excitatory inputs that are inhibited by A1R activation. These data show that
      activating A2ARs increase inhibitory but not excitatory transmission onto neurons
      in the IML. Simultaneous activation of A1Rs and A2ARs therefore could facilitate
      inhibition of the postsynaptic neuron, leading to an overall reduction of
      sympathetic nervous activity.

PMID- 14715947
TI  - Molecular basis of an inherited form of incomplete achromatopsia.
AB  - Mutations in the genes encoding the CNGA3 and CNGB3 subunits of the cyclic
      nucleotide-gated (CNG) channel of cone photoreceptors have been associated with
      autosomal recessive achromatopsia. Here we analyze the molecular basis of
      achromatopsia in two siblings with residual cone function. Psychophysical and
      electroretinographic analyses show that the light sensitivity of the cone system
      is lowered, and the signal transfer from cones to secondary neurons is perturbed.
      Both siblings carry two mutant CNGA3 alleles that give rise to channel subunits
      with different single-amino acid substitutions. Heterologous expression revealed
      that only one mutant forms functional channels, albeit with grossly altered
      properties, including changes in Ca2+ blockage and permeation. Surprisingly,
      coexpression of this mutant subunit with CNGB3 rescues the channel phenotype,
      except for the Ca2+ interaction. We argue that these alterations are responsible
      for the perturbations in light sensitivity and synaptic transmission.

PMID- 14715948
TI  - The impact of suppressive surrounds on chromatic properties of cortical neurons.
AB  - Stimulation of the suppressive surround of a cortical neuron affects the
      responsivity and tuning of the classical receptive field (CRF) on several
      stimulus dimensions. In V1 and V2 of macaques prepared for acute
      electrophysiological experiments, we explored the chromatic sensitivity of the
      surround and its influence on the chromatic tuning of the CRF. We studied
      receptive fields of single neurons with patches of drifting grating of optimal
      spatial frequency and orientation and variable size, modulated along achromatic
      or isoluminant color directions. The responses of most neurons declined as the
      patch was enlarged beyond the optimal size (surround suppression). In V1 the
      suppression evoked by isoluminant gratings was less than one-half that evoked by
      achromatic gratings. Consequently, many cells were most sensitive to achromatic
      modulation when patches just covered the CRF but were most sensitive to
      isoluminant modulation when patches were enlarged to cover the suppressive
      surround. Non-oriented neurons that were strongly chromatically opponent
      generally lacked suppressive surrounds. In V2 most neurons showed equal surround
      suppression from isoluminant gratings and achromatic gratings. This makes the
      relative sensitivity of V2 neurons to achromatic and isoluminant gratings mainly
      independent of the size of the grating. We also measured the chromatic properties
      of the CRF in the presence of differently colored surrounds. In neither V1 nor V2
      did the surround alter the chromatic tuning of the CRF. Cortical mechanisms
      sensitive to chromatic contrast seem to provide little input to the suppressive
      surrounds of V1 neurons but substantial input to those of V2 neurons.

PMID- 14715949
TI  - Functional and genomic changes in the mouse ocular motor system in response to
      light deprivation from birth.
AB  - Previous studies have suggested that abnormal visual experience early in life
      induces ocular motor abnormalities. The purpose of this study was to determine
      how visual deprivation alters the function and gene expression profile of the
      ocular motor system in mice. We measured the effect of dark rearing on eye
      movements, gene expression in the oculomotor nucleus, and contractility of
      isolated extraocular muscles. In vivo eye movement recordings showed decreased
      gains for optokinetic and vestibulo-ocular reflexes, confirming an effect of dark
      rearing on overall ocular motor function. Saccade peak velocities were preserved,
      however, arguing that the quantitative changes in these reflexes were not
      secondary to limitations in force generation. Using microarrays and quantitative
      PCR, we found that dark rearing shifted the oculomotor nucleus transcriptome to a
      state of delayed/arrested development. The expression of 132 genes was altered by
      dark rearing; these genes fit in various functional categories (signal
      transduction, transcription/translation control, metabolism, synaptic function,
      cytoskeleton), and some were known to be associated with neuronal development and
      plasticity. Extraocular muscle contractility was impaired by dark rearing to a
      greater extent than expected from the in vivo ocular motility studies: changes
      included decreased force and shortening speed and evidence of abnormal
      excitability. The results indicate that normal development of the mouse ocular
      motor system and its muscles requires visual experience. The transcriptional
      pattern of arrested development may indicate that vision is required to establish
      the adult pattern, but it also may represent the plastic response of oculomotor
      nuclei to abnormal extraocular muscles.

PMID- 14715950
TI  - Spatial and temporal properties of visual responses in the thalamus of the
      developing ferret.
AB  - Spatiotemporal patterning of neural activity is thought to influence the
      development of connections in the visual pathway. This patterning can arise
      spontaneously or through sensory experience. Here, we use a combination of
      natural and simple stimuli to investigate which elements of the visual
      environment modulate the earliest responses in the primary visual pathway of
      developing ferrets. Recordings were made during the first 2 weeks of visual
      responsiveness, which, in the ferret, overlaps with the period that the eyelids
      have not yet opened. Even when the eyelids are closed, both thalamic and cortical
      activity was found to be temporally modulated under conditions of natural visual
      stimulation. The modulations correlated with temporal changes in stimulus
      contrast but also reflected spatial structure in the visual scene. Simple stimuli
      were used to show that early responses to naturalistic stimuli are influenced by
      the localization and structure of through-the-eyelid receptive fields. The early
      visual responses were also characterized by substantial variability in the
      ability of the cells to detect stimuli of different duration and different
      intensity, in a temporally precise manner. These temporal and spatial properties
      should constrain how plasticity mechanisms interpret naturally patterned
      activity.

PMID- 14715951
TI  - The role of AMPA receptor gating in the development of high-fidelity
      neurotransmission at the calyx of Held synapse.
AB  - During early postnatal development of auditory synapses, the decay time course of
      AMPA receptor (AMPAR) EPSCs accelerates markedly, but the mechanisms underlying
      this process remain uncertain. Using the developing calyx of Held synapse in the
      mouse auditory brainstem, we have examined presynaptic and postsynaptic elements
      that may regulate decay kinetics of AMPAR EPSCs. We found that the decay time
      kinetics was voltage dependent in both immature and mature synapses, being slower
      at positive potentials than negative potentials. By recording evoked miniature
      events in extracellular Ca2+ or Sr2+, we revealed a significant decrease in decay
      time constants of EPSCs as maturation progresses. On the basis of internal and
      external polyamine block of AMPAR EPSCs and immunohistochemistry assays with
      subunit-specific antibodies, we demonstrated that the glutamate receptor (GluR) 2
      subunit is virtually absent at all developmental ages. Antibody staining patterns
      suggest a gradual shift in subunit composition from GluR1- to GluR3/4-dominant
      phenotypes. Kinetic analyses of deactivation, desensitization, and recovery from
      desensitization in outside-out patches in response to ultrafast application of
      glutamate lend supportive evidence that such a shift in the gating phenotype
      likely accounts for the accelerated time course throughout development. Finally,
      by pharmacologically manipulating AMPAR gating and using simulated EPSCs to evoke
      action potentials, we demonstrated that rapid decay kinetics of AMPAR EPSCs is
      essential for this synapse to accommodate high-frequency firing without
      compromising spike amplitude. Hence, developmental alterations in the subunit
      composition likely dictate changes in the time course of AMPAR EPSCs and play an
      indispensable role in the refinement of high-fidelity neurotransmission at the
      calyx of Held synapse.

PMID- 14715952
TI  - Selective effects of potassium elevations on glutamate signaling and action
      potential conduction in hippocampus.
AB  - High-frequency synaptic transmission is depressed by moderate rises in the
      extracellular potassium concentration ([K+]o). Previous reports have indicated
      that depression of action potential signaling may underlie the synaptic
      depression. Here, we investigated the specific contribution of K+-induced action
      potential changes to synaptic depression. We found that glutamatergic
      transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM
      [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that
      slows recovery from inactivation of voltage-gated sodium channels (NaChs),
      interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly.
      Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from
      inactivation. It is unclear from previous studies whether [K+]o-induced action
      potential depression is caused by changes in initiation, reliability, or
      waveform. We investigated these possibilities explicitly. [K+]o-induced afferent
      volley depression was independent of stimulus strength, suggesting that changes
      in action potential initiation do not explain [K+]o-induced depression.
      Measurements of action potentials from single axons revealed that 8 mM [K+]o
      increased conduction failures in a subpopulation of fibers and depressed action
      potential amplitude in all fibers. Together, these changes quantitatively account
      for the afferent volley depression. We estimate that conduction failure explains
      more than half of the synaptic depression observed at 8 mM [K+]o, with the
      remaining depression likely explained by waveform changes. These mechanisms of
      selective sensitivity of glutamate release to [K+]o accumulation represent a
      unique neuromodulatory mechanism and a brake on runaway excitation.

PMID- 14715953
TI  - Gephyrin is critical for glycine receptor clustering but not for the formation of
      functional GABAergic synapses in hippocampal neurons.
AB  - The role of the scaffolding protein gephyrin at hippocampal inhibitory synapses
      is not well understood. A previous study (Kneussel et al., 1999) reported a
      complete loss of synaptic clusters of the major GABA(A)R subunits alpha2 and
      gamma2 in hippocampal neurons lacking gephyrin. In contrast, we show here that
      GABA(A)R alpha2 and gamma2 subunits do cluster at pyramidal synapses in
      hippocampal cultures from gephyrin-/- mice, albeit at reduced levels compared
      with control neurons. Synaptic aggregation of GABA(A)R alpha1 on interneurons was
      identical between the culture types. Furthermore, we recorded miniature IPSCs
      (mIPSCs) from gephyrin-/- neurons. Although the mean mIPSC amplitude was reduced
      (by 23%) compared with control, the frequency of these events was unchanged. Cell
      surface labeling experiments indicated that gephyrin contributes, in part, to
      aggregation but not to insertion or stabilization of GABA(A)R alpha2 and gamma2
      in the plasma membrane. Thus, a major gephyrin-independent component of
      hippocampal inhibitory synapse development must exist. We also report that
      glycine receptors cluster at GABAergic synapses in a subset of hippocampal
      interneurons and pyramidal neurons. Unlike GABA(A)Rs, synaptic clustering of
      glycine receptors was completely abolished in gephyrin-/- neurons. Finally,
      artificial extrasynaptic aggregation of GABA(A)R was able to redistribute and
      cocluster gephyrin by a mechanism requiring a neuron-specific modification or
      intermediary protein. We propose a model of hippocampal inhibitory synapse
      development in which some GABA(A)Rs cluster at synapses by a gephyrin-independent
      mechanism and recruit gephyrin. This clustered gephyrin may then recruit glycine
      receptors, additional GABA(A)Rs, and other signal-transducing components.

PMID- 14715954
TI  - Neural substrates mediating human delay and trace fear conditioning.
AB  - Previous functional magnetic resonance imaging (fMRI) studies with human subjects
      have explored the neural substrates involved in forming associations in Pavlovian
      fear conditioning. Most of these studies used delay procedures, in which the
      conditioned stimulus (CS) and unconditioned stimulus (UCS) coterminate. Less is
      known about brain regions that support trace conditioning, a procedure in which
      an interval of time (trace interval) elapses between CS termination and UCS
      onset. Previous work suggests significant overlap in the neural circuitry
      supporting delay and trace fear conditioning, although trace conditioning
      requires recruitment of additional brain regions. In the present event-related
      fMRI study, skin conductance and continuous measures of UCS expectancy were
      recorded concurrently with whole-brain blood oxygenation level-dependent (BOLD)
      imaging during direct comparison of delay and trace discrimination learning.
      Significant activation was observed within the visual cortex for all CSs.
      Anterior cingulate and medial thalamic activity reflected associative learning
      common to both delay and trace procedures. Activations within the supplementary
      motor area (SMA), frontal operculum, middle frontal gyri, and inferior parietal
      lobule were specifically associated with trace interval processing. The
      hippocampus displayed BOLD signal increases early in training during all
      conditions; however, differences were observed in hippocampal response magnitude
      related to the accuracy of predicting UCS presentations. These results
      demonstrate overlapping patterns of activation within the anterior cingulate,
      medial thalamus, and visual cortex during delay and trace procedures, with
      additional recruitment of the hippocampus, SMA, frontal operculum, middle frontal
      gyrus, and inferior parietal lobule during trace conditioning. These data suggest
      that the hippocampus codes temporal information during trace conditioning,
      whereas brain regions supporting working memory processes maintain the CS-UCS
      representation during the trace interval.

PMID- 14715955
TI  - Persistent progenitors at the retinal margin of ptc+/- mice.
AB  - The hedgehog signaling pathway is a key regulator of neural development,
      affecting both proliferation and differentiation of neural progenitors. Sonic
      hedgehog (Shh) is a mitogenic factor for retinal progenitors in vitro. To
      determine whether this signaling system is important in vivo for regulating
      retinal progenitor proliferation, we analyzed mice with a single functional
      allele of the Shh receptor patched (ptc). We found that ptc+/- mice had increased
      numbers of neural progenitors at every stage of retinal development that we
      examined. In addition, these mice had persistent progenitors at the retinal
      margin for up to 3 months of age, reminiscent of the ciliary marginal zone of
      lower vertebrates. To test whether the progenitors at the retinal margin of ptc+/
      mice could be induced to regenerate retinal neurons in response to damage, we
      bred ptc+/- mice onto a retinal degeneration background (pro23his rhodopsin
      transgenic) and labeled newly generated cells with combined immunohistochemistry
      for bromodeoxyuridine and retinal neuron and photoreceptor-specific markers. We
      found newly generated neurons and photoreceptors at the retinal margin in ptc+/
      ;pro23his mice. We propose that the Shh pathway may act as a regulator of both
      prenatal and postnatal retinal growth.

PMID- 14715956
TI  - Neurite outgrowth by the alternatively spliced region of human tenascin-C is
      mediated by neuronal alpha7beta1 integrin.
AB  - The region of tenascin-C containing only alternately spliced fibronectin type-III
      repeat D (fnD) increases neurite outgrowth by itself and also as part of tenascin
      C. We previously localized the active site within fnD to an eight amino acid
      sequence unique to tenascin-C, VFDNFVLK, and showed that the amino acids FD and
      FV are required for activity. The purpose of this study was to identify the
      neuronal receptor that interacts with VFDNFVLK and to investigate the hypothesis
      that FD and FV are important for receptor binding. Function-blocking antibodies
      against both alpha7 and beta1 integrin subunits were found to abolish VFDNFVLK
      mediated process extension from cerebellar granule neurons. VFDNFVLK but not its
      mutant, VSPNGSLK, induced clustering of neuronal beta1 integrin immunoreactivity.
      This strongly implicates FD and FV as important structural elements for receptor
      activation. Moreover, biochemical experiments revealed an association of the
      alpha7beta1 integrin with tenascin-C peptides containing the VFDNFVLK sequence
      but not with peptides with alterations in FD and/or FV. These findings are the
      first to provide evidence that the alpha7beta1 integrin mediates a response to
      tenascin-C and the first to demonstrate a functional role for the alpha7beta1
      integrin receptor in CNS neurons.

PMID- 14715957
TI  - Widespread thalamic terminations of fibers arising in the superficial medullary
      dorsal horn of monkeys and their relation to calbindin immunoreactivity.
AB  - The relay of pain fibers from the spinal and medullary dorsal horn in the
      thalamus has become a controversial issue. This study analyzed the relationship
      of fibers arising in lamina I to nuclei in and around the caudal pole of the
      ventral posterior nuclear complex and especially to a zone of calbindin-dense
      immunoreactivity (VMpo) identified by some authors as the sole thalamic relay for
      these fibers. We show that the densest zone of calbindin immunoreactivity is part
      of a more extensive, calbindin-immunoreactive region that lies well within the
      medial tip of the ventral posterior medial nucleus (VPM), as delineated by other
      staining methods, and prove that the use of different anti-calbindin antibodies
      cannot account for differences in interpretations of the organization of the
      posterior thalamic region. By combining immunocytochemical staining with
      anterograde tracing from injections involving lamina I, we demonstrate widespread
      fiber terminations that are not restricted to the calbindin-rich medial tip of
      VPM and show that the lamina I arising fibers are not themselves calbindin
      immunoreactive. This study disproves the existence of VMpo as an independent
      thalamic pain nucleus or as a specific relay in the ascending pain system.

PMID- 14715958
TI  - Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia.
AB  - The cyclooxygenases COX-1 and COX-2 catalyze the first committed step of
      prostaglandin synthesis from arachidonic acid. Previous studies in rodent stroke
      models have shown that the inducible COX-2 isoform promotes neuronal injury, and
      the administration of COX-2 inhibitors reduces infarct volume. We investigated
      the function of PGE2, a principal prostaglandin product of COX-2 enzymatic
      activity, in neuronal survival in cerebral ischemia. PGE2 exerts its downstream
      effects by signaling through a class of four distinct G-protein-coupled EP
      receptors (for E-prostanoid: EP1, EP2, EP3, and EP4) that have divergent effects
      on cAMP and phosphoinositol turnover and different anatomical distributions in
      brain. The EP2 receptor subtype is abundantly expressed in cerebral cortex,
      striatum, and hippocampus, and is positively coupled to cAMP production. In vitro
      studies of dispersed neurons and organotypic hippocampal cultures demonstrated
      that activation of the EP2 receptor was neuroprotective in paradigms of NMDA
      toxicity and oxygen glucose deprivation. Pharmacologic blockade of EP2 signaling
      by inhibition of protein kinase A activation reversed this protective effect,
      suggesting that EP2-mediated neuroprotection is dependent on cAMP signaling. In
      the middle cerebral artery occlusion-reperfusion model of transient forebrain
      ischemia, genetic deletion of the EP2 receptor significantly increased cerebral
      infarction in cerebral cortex and subcortical structures. These studies indicate
      that activation of the PGE2 EP2 receptor can protect against excitotoxic and
      anoxic injury in a cAMP-dependent manner. Taken together, these data suggest a
      novel mechanism of neuroprotection mediated by a dominant PGE2 receptor subtype
      in brain that may provide a target for therapeutic intervention.

PMID- 14715959
TI  - Huntingtin bodies sequester vesicle-associated proteins by a polyproline
      dependent interaction.
AB  - Polyglutamine expansion in the N terminus of huntingtin (htt) causes selective
      neuronal dysfunction and cell death by unknown mechanisms. Truncated htt
      expressed in vitro produced htt immunoreactive cytoplasmic bodies (htt bodies).
      The fibrillar core of the mutant htt body resisted protease treatment and
      contained cathepsin D, ubiquitin, and heat shock protein (HSP) 40. The shell of
      the htt body was composed of globules 14-34 nm in diameter and was protease
      sensitive. HSP70, proteasome, dynamin, and the htt binding partners htt
      interacting protein 1 (HIP1), SH3-containing Grb2-like protein (SH3GL3), and
      14.7K-interacting protein were reduced in their normal location and redistributed
      to the shell. Removal of a series of prolines adjacent to the polyglutamine
      region in htt blocked formation of the shell of the htt body and redistribution
      of dynamin, HIP1, SH3GL3, and proteasome to it. Internalization of transferrin
      was impaired in cells that formed htt bodies. In cortical neurons of Huntington's
      disease patients with early stage pathology, dynamin immunoreactivity accumulated
      in cytoplasmic bodies. Results suggest that accumulation of a nonfibrillar form
      of mutant htt in the cytoplasm contributes to neuronal dysfunction by
      sequestering proteins involved in vesicle trafficking.

PMID- 14715960
TI  - Active zone localization of presynaptic calcium channels encoded by the cacophony
      locus of Drosophila.
AB  - Presynaptic calcium channels play a central role in chemical synaptic
      transmission by providing the calcium trigger for evoked neurotransmitter
      release. These voltage-gated calcium channels are composed of a primary
      structural subunit, alpha1, as well as auxiliary beta and alpha2delta subunits.
      Our previous genetic, molecular, and functional analysis has shown that the
      cacophony (cac) gene encodes a primary presynaptic calcium channel alpha1 subunit
      in Drosophila. Here we report that transgenic expression of a cac-encoded alpha1
      subunit fused with enhanced green fluorescent protein efficiently rescues cac
      lethal mutations and allows in vivo analysis of calcium channel localization at
      active zones. The results reported here further characterize the primary role of
      cac-encoded calcium channels in neurotransmitter release. In addition, these
      studies provide a unique genetic tool for live imaging of functional presynaptic
      calcium channels in vivo and define a molecular marker for immunolocalization of
      other presynaptic proteins relative to active zones. These findings are expected
      to facilitate additional analysis of synaptic development and function in this
      important model system.

PMID- 14715961
TI  - Neuronal birthdate-specific gene transfer with adenoviral vectors.
AB  - The multilayered structure of the cerebral cortex has been studied in detail.
      Early-born neurons migrate into the inner layer and late-born neurons migrate
      into more superficial layers, thus establishing an inside-out gradient. The
      progenitor cells appear to acquire layer-specific properties at the time of
      neuronal birth; however, the molecular mechanisms of cell-fate acquisition are
      still unclear, because it has been difficult to identify a cohort of birthdate
      related progenitor cells. Using replication-defective adenoviral vectors, we
      successfully performed "pulse gene transfer" into progenitor cells in a neuronal
      birthdate-specific manner. When adenoviral vectors were injected into the
      midbrain ventricle of mouse embryos between embryonic day 10.5 (E10.5) and E14.5,
      the adenoviral vectors introduced a foreign gene into a specific cohort of
      birthdate-related progenitor cells. The virally infected cohorts developed
      normally into cortical neurons and formed the canonical cortical layers in an
      inside-out manner. This technique allows us to distinguish a cohort of birthdate
      related progenitor cells from other progenitor cells with different birthdates
      and to introduce a foreign gene into specific subsets of cortical layers by
      performing adenoviral injection at specific times. This adenovirus-meditated gene
      transfer technique will enable us to examine the properties of each subset of
      progenitor cells that share the same neuronal birthdate.

PMID- 14715962
TI  - Histopathology and immunohistochemistry of canine distemper virus-induced footpad
      hyperkeratosis (hard Pad disease) in dogs with natural canine distemper.
AB  - Hard pad disease represents an uncommon manifestation of canine distemper virus
      (CDV) infection with a still uncertain pathogenesis. To study the pathogenesis of
      this uncommon, virally induced cutaneous lesion, the footpads of 19 dogs with
      naturally occurring distemper were investigated for histologic changes and
      distribution pattern of CDV antigen. All dogs displayed clinical signs of
      distemper, which had lasted from 10 to 75 days. Overt digital hyperkeratosis was
      observed in 12 animals (group A), whereas the footpads of the remaining seven
      dogs appeared normal macroscopically (group B). Orthokeratotic hyperkeratosis
      (12/12; 100%), irregular acanthosis (11/12; 92%), thickened rete ridges (10/12;
      83%), and mild mononuclear perivascular (10/ 12; 83%) and periadnexal (7/12; 58%)
      dermatitis were the most common findings in dogs with hard pad disease.
      Surprisingly, orthokeratotic hyperkeratosis (5/7; 71%), irregular acanthosis
      (5/7; 71%), and thickened rete ridges (4/7; 57%) were also seen in the dogs
      without clinical evidence of digital hyperkeratosis. CDV-specific inclusion
      bodies and ballooning degeneration were not observed in the footpad epidermis of
      the 19 dogs. Immunohis-tochemistry revealed that CDV antigen was most frequently
      found in the stratum spinosum and granulosum and in the epithelial cells of the
      eccrine sweat glands and only rarely in the basal layer. Fibroblasts, pericytes,
      endothelial cells, and hair follicles were also positive in some animals. Despite
      the obvious difference regarding the macroscopic picture, the microscopic changes
      were less prominent between the animal groups. The selective infection of
      keratinocytes in the stratum spinosum might be the key event for the development
      of hard pad disease in the dog.

PMID- 14715963
TI  - Morphology, immunohistochemistry, and genetic alterations in dog astrocytomas.
AB  - Astrocytoma is one of the most common tumors of the central nervous system in
      animals. Of the domesticated animal species, most examples are seen in dogs, and
      the spectrum that has been described is quiet broad. Previous studies have
      revealed morphologic similarities between human and animal astrocytomas. Human
      astrocytomas are often associated with genetic alterations that determine the
      clinical behavior and therapy outcome. The purpose of this study was to further
      characterize astrocytomas in dogs and to determine whether there are genetic
      changes similar to those in the human counterpart.

PMID- 14715964
TI  - Olivopontocerebellar atrophy in two adult cats, sporadic cases or new genetic
      entity.
AB  - Two otherwise healthy adult cats were presented with progressive cerebellar signs
      of different severity. Owners requested euthanasia. Necropsy disclosed whole
      cerebellum and pontine atrophy, with a severity paralleling the neurologic
      dysfunction. We used cell type-specific immunolabelings to characterize the
      lesions. The severity of the cerebellar cortex atrophy followed a general
      gradient from the midvermis toward the hemispheres and a local gradient from the
      depth of the folia toward their tip. Along these gradients, Purkinje cells were
      the first to disappear, followed by basket, Golgi, and stellate cells, and
      eventually by granule cells. Bergmann glia cells and unipolar brush cells were
      preserved. Pontine nuclei and the olivary complex were also severely depopulated.
      Neurons in the cerebellar nuclei, vestibular nuclei, and other cerebellar system
      associated structures were preserved, as well as substantia nigra.
      Olivopontocerebellar atrophy (OPCA) in a domestic animal species was rarely
      reported. Some features allow tentative linking to either familial or sporadic
      OPCA of humans. However, the ordered disappearance of all cortical neuronal types
      has never been described before. Either this entity is cat specific or it might
      pinpoint the need for increased knowledge about differential gene expression
      depending on genetic background, i.e., among different species. It also would
      open prospects about gene product interactions within neurons.

PMID- 14715965
TI  - Osteoclast numbers in Lewis rats with adjuvant-induced arthritis: identification
      of preferred sites and parameters for rapid quantitative analysis.
AB  - This study defined the best site for quantifying osteoclasts in male Lewis rats
      with mycobacteria-induced adjuvant arthritis. Hind paw sections of normal and
      arthritic rats (n = 6 per group) taken 7 days after disease onset were stained
      for osteoclasts using an anti-human cathepsin K primary antibody. Erosions and
      osteoclasts were assessed using semiquantitative scores (entire section) and
      quantitative measures (in calcaneus, navicular tarsal, and tibia). Bone area in
      arthritic rats was significantly reduced (P </= 0.05) by 39-55%, with the
      greatest decrease in the tarsal. Osteoclasts in arthritic rats were significantly
      increased (P </= 0.05) relative to normal in calcaneus (sevenfold), tarsal (194
      fold), and tibia (threefold). The most useful quantitative indices were bone area
      and total osteoclasts, both defined as a percentage of total area measured.
      Semiquantitative scores for bone erosion and osteoclasts paralleled the
      quantitative indices. These data show that the navicular tarsal is the most
      sensitive site at which to assess arthritis in rats with this variant of adjuvant
      induced arthritis.

PMID- 14715966
TI  - Immunohistochemical evaluation of mononuclear infiltrates in canine lupoid
      onychodystrophy.
AB  - Claw biopsy samples of 11 dogs with lupoid onychodystrophy were evaluated. They
      were stained with hematoxylin and eosin and with antibodies against CD 3 as a T
      cell marker, BLA 36 and HM 57 (CD 79alpha) as B-cell markers, and lysozyme, Mac
      387, and major histocompatibility complex (MHC) class II as a marker for
      histiocytes using an immunoperoxidase and avidin-biotin technique. Inflammatory
      cells were counted in five high-power fields. The inflammatory infiltrate
      comprised predominantly B cells and T cells. Macrophages were typically only
      present in small numbers. CD 3, BLA 36, lysozyme, and MHC class II preserved
      significant antigenicity during formalin fixation and short decalcification for
      24-48 hours, whereas CD 79alpha and particularly Mac 387 seemed to be more
      susceptible to denaturation by the decalcification process.

PMID- 14715967
TI  - Immunoglobulin-A nephropathy with crescentic glomerulonephritis in a pigtailed
      macaque (Macaca nemestrina).
AB  - A 4-year-old female pigtailed macaque (Macaca nemestrina), experimentally
      coinfected with simian immunodeficiency virus (SIVmac251) and Mycobacterium
      bovis(bacillus Calmette-Guerin), was euthanatized 1 year after infection because
      of weight loss and labored breathing. On gross examination, both kidneys were
      found to be markedly enlarged (right: 54.7 g and left: 51.7 g; normal < 20 g).
      Renal lesions were evaluated by histopathologic, immunohistochemical, and
      ultrastructural methods. Light microscopy revealed that the glomeruli were
      diffusely hypercellular with expansion of the mesangial matrix, and crescent
      formation affected approximately 60% of the glomeruli. By immunohistochemical
      evaluation, it was found that the crescents were composed principally of
      macrophages, as seen by CD68 (KP1), MRP8, MAC387, and HAM56 expression. Electron
      microscopic examination of the glomeruli revealed extensive intramembranous,
      subendothelial, and mesangial electron-dense deposits and multifocal fusion of
      the visceral epithelial foot processes. Immunofluorescence, used to determine the
      composition of the electron-dense deposits, revealed diffuse granular mesangial
      and capillary staining for immunoglobulin A (IgA). The renal changes described in
      this case report are most consistent with the findings of crescentic
      gloerulonephritis with IgA immune complex deposition in the glomerular basement
      membrane and mesangium as described in humans with IgA nephropathy.

PMID- 14715968
TI  - Experimental transmission of a herpesvirus in Greek tortoises (Testudo graeca).
AB  - An experimental transmission study aimed at fulfilling Koch's postulates for a
      herpesvirus-associated stomatitis-rhinitis in Mediterranean tortoises is
      presented. Clinical, pathologic, serologic, and molecular studies were performed
      linking tortoise herpesvirus with the pathogenesis of stomatitis-rhinitis. Four
      adult Greek tortoises received either intranasally or intramuscularly two
      tortoise herpesvirus isolates by primary experimental infection and secondary
      challenge 11 months later. After the primary experimental infection and the
      secondary challenge, clinical signs of illness developed, which included
      conjunctivitis, diphtheritic oral plaques, and oral discharge. At 4 weeks after
      the secondary challenge, all tortoises were humanely euthanatized and evaluated.
      Although neutralizing antibodies developed after the primary experimental
      infection, they apparently did not prevent the later development of recurrent
      clinical signs. Polymerase chain reaction (PCR) and reverse transcription-PCR
      analyses allowed sensitive characterization of the systemic distribution of the
      herpesvirus DNA sequences and their presence in the cranial nerves and brains of
      the infected tortoises. Despite the failure to recover the herpesviruses used in
      the transmission study, the findings support the premise that tortoise herpes
      virus is a primary pathogen of Greek tortoises.

PMID- 14715969
TI  - Nonsuppurative encephalitis in piglets after experimental inoculation of Japanese
      encephalitis flavivirus isolated from pigs.
AB  - Nonsuppurative encephalitis was experimentally induced in 3-week-old piglets by a
      single intravenous inoculation of either of two strains (IB 2001 or AS-6) of
      Japanese encephalitis flavivirus (JEV) isolated from field pigs. The lesions,
      which consisted of neuronal necrosis, neuronophagia, glial nodules, and perivas
      cular cuffing, were distributed in the cerebrum, midbrain, pons, medulla
      oblongata, and cerebellum, particularly in the gray matter of the frontal and
      temporal lobes and thalamus. The gray matter of the spinal cord of piglets that
      were given the AS-6 strain also was affected. JEV antigen was
      immunohistochemically detected in the cytoplasm of the nerve cells in the cortex
      of the frontal and temporal lobes and in the gray matter of the thalamus and
      midbrain. Two JEV strains isolated from field pigs exhibited neurovirulence,
      inducing nonsup-purative encephalitis in piglets.

PMID- 14715970
TI  - Testicular atrophy after bile duct ligation in chickens.
AB  - Testicular atrophy associated with biliary obstruction in chickens, produced by
      the ligation of both extrahepatic bile ducts, was examined grossly,
      histologically, immunohistochemically, and ultrastructurally. Grossly, reduction
      in testicular size and volume was evident in chickens that underwent bile duct
      ligation (BDL). Histologically, there was marked reduction in tubular diameter,
      peritubular fibrosis, loss of spermatogenic cells, and tubules lined only by
      Sertoli cells. In addition, Leydig cells, which accumulated in the interstitium
      of the testes, contained numerous large lipid vacuoles, as determined by electron
      microscopy. These features suggest that BDL in chickens causes hypogonadism and
      low serum testosterone.

PMID- 14715971
TI  - Primitive neuroectodermal neoplasia in coho salmon, Oncorhynchus kisutch.
AB  - Twelve coho salmon, approximately 8 weeks old, were each observed to have a
      single neoplasm involving the dorsolateral axial skeletal musculature. The
      neoplasm was closely associated with the vertebrae in all cases. The neoplasm was
      composed of islands containing small cells with round and occasional spindeloid
      morphology. Neoplastic cells had basophilic cytoplasm and vesicular nuclei. These
      cells exhibited immuno-positivity only for vimentin and S-100 protein.
      Ultrastructurally, neoplastic cells had nuclei with a predominance of
      euchromatin, cytoplasm containing marked amounts of rough endoplasmic reticulum,
      scant amounts of smooth endoplasmic reticulum, and scattered mitochondria.
      Rudimentary cell junctions were occasionally observed between adjacent neoplastic
      cells. Based on the close association of these neoplasms with the vertebrae as
      well as the histologic, ultrastructural, and immunohistochemical findings, these
      neoplasms were considered to all be primitive neuroectodermal neoplasms.

PMID- 14715972
TI  - Rete testis mucinous adenocarcinoma in a dog.
AB  - A bilateral testicular neoplasm from an 11-year-old mixed-breed male dog was
      removed surgically and examined histologically. The neoplasm was nonencapsulated
      and composed of acinar and tubular structures lined by one or more layers of
      neoplastic polyhedral epithelial cells with an abundant mucinous secretion. On
      histochemistry, all neoplastic cells and associated secretions were periodic acid
      Schiff positive. Some neoplastic cells and all associated secretions were
      positive on mucicarmine stain, and some neoplastic cells, all the stroma, and
      associated secretions were positive on alcian blue stain. On
      immunohistochemistry, the neoplastic cells had strong diffuse cytoplasmic
      immunoreactivity for cytokeratin and vimentin, weak scattered cytoplasmic
      immunoreactivity for carcinoembryonic antigen and neuron-specific enolase, and no
      immunoreactivity for S-100. On the basis of histopathology, histochemistry, and
      immunohistochemical findings, a diagnosis of mucinous adenocarcinoma of rete
      testis was made. Rete testis adenocarcinoma is a well known but very rare
      neoplasm in humans. To our knowledge, this is the first report of the mucinous
      variant of adenocarcinoma of the rete testis in a dog.

PMID- 14715973
TI  - Failure to detect prion protein (PrPres) by immunohistochemistry in striated
      muscle tissues of animals experimentally inoculated with agents of transmissible
      spongiform encephalopathy.
AB  - Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases.
      Infection by the causative agent, a prion, induces accumulations of an abnormal
      form of prion protein (PrP(res)) in tissues of nervous and lymphoid systems.
      Presence of characteristic histopathologic changes (spongiform encephalopathy)
      and detection of protease-resistant PrP(res) in neural and lymphoid tissues are
      the basis of currently available methods for diagnosis of TSEs. In this study,
      samples of striated muscle tissues (tongue, heart, diaphragm, and masseter
      muscle) from 20 animals (cattle, sheep, elk, and raccoons) were examined for
      PrP(res) by immunohistochemistry (IHC). All the animals had developed a TSE after
      experimental inoculation. PrP(res) was found by IHC in the brain but not in the
      muscle tissues of all the animals examined. These findings are contradictory to
      recently published reports of laboratory animals with TSEs, where these altered
      prion proteins were detected in tongue and other striated muscles. Further
      testing of muscle tissues is needed to confirm the findings of the present study.

PMID- 14715974
TI  - Inositol 1,4,5-triphosphate receptor protein immunohistochemistry of cerebellar
      Purkinje cells in two dogs with hypoglycemia.
AB  - Immunohistochemical study was performed on cerebellar Purkinje cells of two dogs
      with hypoglycemia using an antibody against the inositol 1,4,5-triphosphate
      receptor that is identical to the cerebellar Purkinje cell glycoprotein P(400)
      (P(400)/InsP(3)R). In the cerebellar neocortex of an acute case of hypoglycemia,
      the P(400)/InsP(3)R staining of hypoglycemic Purkinje cells was heterogeneous:
      some peripheral dendrites, including spiny branchlets, were negative and others
      were stained with various intensities, although Purkinje cells were
      morphologically intact by hematoxylin and eosin (HE) stain. In a chronic case of
      hypoglycemia, almost all the dendrites of Purkinje cells of both the neo- and
      archicortex of the cerebellum were not stained with the P(400)/InsP(3)R antibody.
      This is in contrast to the normal dog where Purkinje cell bodies, axons, and
      dendrites, including spiny branchlets, are intensely stained by the
      P(400)/InsP(3)R antibody. These results suggest that P(400)/InsP(3)R
      immunolabeling of Purkinje cells decreased, despite their morphology being
      preserved by HE stain, and that the function of P(400)/InsP(3)R, especially in
      spiny branchlets that receive inputs originating from axon terminals of parallel
      fibers, may be impaired in hypoglycemia.

PMID- 14715975
TI  - Risk adjustment effect on stroke clinical trials.
AB  - BACKGROUND AND PURPOSE: The ischemic stroke population is heterogeneous. Even in
      balanced randomized trials, patient heterogeneity biases estimates of the
      treatment effect toward no effect when dichotomous end points are used. Risk
      adjustment statistically addresses some of the heterogeneity and can reduce bias
      in the treatment effect estimate. The purpose of this study was to estimate the
      treatment effect of tissue plasminogen activator (tPA) in the National Institute
      of Neurological Disorders and Stroke (NINDS) tPA data set with and without
      adjustment for baseline differences. METHODS: Using a prespecified predictive
      model, we calculated unadjusted and risk-adjusted odds ratios (ORs) for favorable
      outcome for the Barthel Index, National Institutes of Health Stroke Scale, and
      Glasgow Outcome Scale for the patients in the NINDS tPA stroke trial. To assess
      the importance of the difference, a new sample size was calculated through the
      use of the risk-adjusted analysis. RESULTS: We analyzed 615 subjects. The ORs for
      the Barthel Index were 1.76 (unadjusted) and 2.04 (adjusted). The National
      Institutes of Health Stroke Scale and Glasgow Outcome Scale analyses also
      demonstrated increased ORs after adjustment. The estimated sample size required
      for the adjusted comparison was 13% smaller than the unadjusted sample.
      CONCLUSIONS: Risk adjustment in this data set suggests that the true treatment
      effect was larger than estimated by the unadjusted analysis. Stroke clinical
      trials should include prospective risk adjustment methodologies.

PMID- 14715976
TI  - Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia
      in rats.
AB  - BACKGROUND AND PURPOSE: Hyperbaric oxygenation (HBO) is an attractive procedure
      that has been used frequently in cerebral ischemia. However, depending on the
      model of cerebral ischemia and HBO protocol, different and conflicting results
      were obtained in the past. This study was undertaken to reevaluate the effects of
      single administration of HBO in 2 models of acute cerebral ischemia: transient or
      permanent focal ischemia in rats. A comparison of the 2 ischemia models was
      undertaken to search for a putative therapeutic window. METHODS: The intraluminal
      middle cerebral artery occlusion model (MCAO) was used. The effect of single HBO
      therapy (3 atm absolute, 60 minutes) on transient or permanent focal ischemia,
      when applied at different times (3, 6, or 12 hours) after MCAO, was investigated;
      infarct volume and neurological deficits were assessed at 24 hours and up to 7
      days. RESULTS: HBO had neuroprotective effects on transient MCAO when HBO was
      initiated within the first 6 hours, while it aggravated the ischemic injury
      histologically and clinically when initiated 12 hours after MCAO. In permanent
      MCAO, HBO did not reduce tissue damage regardless of the timing of therapy.
      CONCLUSIONS: HBO is highly efficient in reducing infarct volume and improving
      neurobehavioral outcome in transient MCAO within the first 6 hours. HBO at later
      time points (>or=12 hours) is harmful by increasing infarct volume. In permanent
      MCAO, HBO failed to improve infarct volume and clinical outcome.

PMID- 14715977
TI  - Influence of recanalization on outcome in dural sinus thrombosis: a prospective
      study.
AB  - BACKGROUND AND PURPOSE: Recanalization in dural sinus thrombosis (DST) has been
      observed previously; however, systematic prospective data are lacking. The
      influence of recanalization on DST outcome has not yet been thoroughly evaluated.
      METHODS: Thirty-seven consecutive patients with DST were prospectively examined.
      Neurological deficits were graded with the National Institutes of Health Stroke
      Scale (NIHSS) on hospital admission and discharge. Functional outcome was
      assessed with the modified Rankin Scale (mRS) on hospital discharge and after 12
      months. All patients were treated with intravenous heparin in the acute stage of
      illness, followed by oral anticoagulation for 12 months. Imaging follow-up with
      MR angiography and, in a few cases, with CT or conventional angiography was
      performed on hospital discharge and after 6 and 12 months. RESULTS: Twelve-month
      functional outcome was excellent in 89% of patients with an mRS of 0 or 1. A
      recanalization rate of 60% was already observed on hospital discharge (22+/-6
      days); thereafter, recanalization rates increased insignificantly. Early
      recanalization was not related to NIHSS score on hospital discharge or an mRS of
      0 on discharge or after 12 months. CONCLUSIONS: We found a high frequency of
      early recanalization but without influence on clinical outcome parameters.
      Frequent imaging follow-ups in DST are not useful because they provide no
      information on patient outcome.

PMID- 14715978
TI  - Investing in people.

PMID- 14715979
TI  - Planetary science. A tale of two landings, one orbiting.

PMID- 14715981
TI  - Astrophysics. Double pulsar gives astrophysicists many-faceted thrills.

PMID- 14715980
TI  - Planetary science. A surprisingly ancient cometary visage.

PMID- 14715982
TI  - Toxicology. Salmon survey stokes debate about farmed fish.

PMID- 14715983
TI  - High-energy physics. Once again, muons defy reigning theory.

PMID- 14715984
TI  - Russia. Political tussle looms over private RD center.

PMID- 14715985
TI  - Infectious diseases. First U.S. case of mad cow sharpens debate over testing.

PMID- 14715986
TI  - Synthetic biology. Microbes made to order.

PMID- 14715987
TI  - Synthetic biology. Time for a synthetic biology Asilomar?

PMID- 14715988
TI  - Nuclear waste. Deep repositories: out of sight, out of terrorists' reach.

PMID- 14715989
TI  - Astrophysics. Wanted: one good cosmic blast to shake the neighborhood.

PMID- 14715990
TI  - How unique is the rice transcriptome?

PMID- 14715991
TI  - Another grand challenge: mental health.

PMID- 14715992
TI  - The grand challenge of birth control.

PMID- 14715993
TI  - The effects of manganese in air.

PMID- 14715994
TI  - Comment on "Molecular phylogenies link rates of evolution and speciation" (I).

PMID- 14715995
TI  - Comment on "Molecular phylogenies link rates of evolution and speciation" (II).

PMID- 14715997
TI  - Environment. Climate change science: adapt, mitigate, or ignore?

PMID- 14715998
TI  - Paleoclimate. A better radiocarbon clock.

PMID- 14716000
TI  - Planetary science. Weak faults--rotten cores.

PMID- 14715999
TI  - Neuroscience. Calcium and CREST for healthy dendrites.

PMID- 14716001
TI  - Molecular biology. Ring around the retroelement.

PMID- 14716002
TI  - Molecular biology. New Year's resolution--resolving resolvases.

PMID- 14716003
TI  - How enzymes work: analysis by modern rate theory and computer simulations.
AB  - Advances in transition state theory and computer simulations are providing new
      insights into the sources of enzyme catalysis. Both lowering of the activation
      free energy and changes in the generalized transmission coefficient (recrossing
      of the transition state, tunneling, and nonequilibrium contributions) can play a
      role. A framework for understanding these effects is presented, and the
      contributions of the different factors, as illustrated by specific enzymes, are
      identified and quantified by computer simulations. The resulting understanding of
      enzyme catalysis is used to comment on alternative proposals of how enzymes work.

PMID- 14716004
TI  - Borate minerals stabilize ribose.

PMID- 14716006
TI  - 14C activity and global carbon cycle changes over the past 50,000 years.
AB  - A series of 14C measurements in Ocean Drilling Program cores from the tropical
      Cariaco Basin, which have been correlated to the annual-layer counted chronology
      for the Greenland Ice Sheet Project 2 (GISP2) ice core, provides a high
      resolution calibration of the radiocarbon time scale back to 50,000 years before
      the present. Independent radiometric dating of events correlated to GISP2
      suggests that the calibration is accurate. Reconstructed 14C activities varied
      substantially during the last glacial period, including sharp peaks synchronous
      with the Laschamp and Mono Lake geomagnetic field intensity minimal and
      cosmogenic nuclide peaks in ice cores and marine sediments. Simulations with a
      geochemical box model suggest that much of the variability can be explained by
      geomagnetically modulated changes in 14C production rate together with plausible
      changes in deep-ocean ventilation and the global carbon cycle during glaciation.

PMID- 14716005
TI  - Dendrite development regulated by CREST, a calcium-regulated transcriptional
      activator.
AB  - The lasting effects of neuronal activity on brain development involve calcium
      dependent gene expression. Using a strategy called transactivator trap, we cloned
      a calcium-responsive transactivator called CREST (for calcium-responsive
      transactivator). CREST is a SYT-related nuclear protein that interacts with
      adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB)
      binding protein (CBP) and is expressed in the developing brain. Mice that have a
      targeted disruption of the crest gene are viable but display defects in cortical
      and hippocampal dendrite development. Cortical neurons from crest mutant mice are
      compromised in calcium-dependent dendritic growth. Thus, calcium activation of
      CREST-mediated transcription helps regulate neuronal morphogenesis.

PMID- 14716007
TI  - Abiotic forcing of plankton evolution in the Cenozoic.
AB  - We characterize the evolutionary radiation of planktic foraminifera by the test
      size distributions of entire assemblages in more than 500 Cenozoic marine
      sediment samples, including more than 1 million tests. Calibration of Holocene
      size patterns with environmental parameters and comparisons with Cenozoic
      paleoproxy data show a consistently positive correlation between test size and
      surface-water stratification intensity. We infer that the observed
      macroevolutionary increase in test size of planktic foraminifera through the
      Cenozoic was an adaptive response to intensifying surface-water stratification in
      low latitudes, which was driven by polar cooling.

PMID- 14716008
TI  - Widespread intense turbulent mixing in the Southern Ocean.
AB  - Observations of internal wave velocity fluctuations show that enhanced turbulent
      mixing over rough topography in the Southern Ocean is remarkably intense and
      widespread. Mixing rates exceeding background values by a factor of 10 to 1000
      are common above complex bathymetry over a distance of 2000 to 3000 kilometers at
      depths greater than 500 to 1000 meters. This suggests that turbulent mixing in
      the Southern Ocean may contribute crucially to driving the upward transport of
      water closing the ocean's meridional overturning circulation, and thus needs to
      be represented in numerical simulations of the global ocean circulation and the
      spreading of biogeochemical tracers.

PMID- 14716009
TI  - Virus-based toolkit for the directed synthesis of magnetic and semiconducting
      nanowires.
AB  - We report a virus-based scaffold for the synthesis of single-crystal ZnS, CdS,
      and freestanding chemically ordered CoPt and FePt nanowires, with the means of
      modifying substrate specificity through standard biological methods. Peptides
      (selected through an evolutionary screening process) that exhibit control of
      composition, size, and phase during nanoparticle nucleation have been expressed
      on the highly ordered filamentous capsid of the M13 bacteriophage. The
      incorporation of specific, nucleating peptides into the generic scaffold of the
      M13 coat structure provides a viable template for the directed synthesis of
      semiconducting and magnetic materials. Removal of the viral template by means of
      annealing promoted oriented aggregation-based crystal growth, forming individual
      crystalline nanowires. The unique ability to interchange substrate-specific
      peptides into the linear self-assembled filamentous construct of the M13 virus
      introduces a material tunability that has not been seen in previous synthetic
      routes. Therefore, this system provides a genetic toolkit for growing and
      organizing nanowires from semiconducting and magnetic materials.

PMID- 14716010
TI  - Boron nitride nanomesh.
AB  - A highly regular mesh of hexagonal boron nitride with a 3-nanometer periodicity
      and a 2-nanometer hole size was formed by self-assembly on a Rh(111) single
      crystalline surface. Two layers of mesh cover the surface uniformly after high
      temperature exposure of the clean rhodium surface to borazine (HBNH)3. The two
      layers are offset in such a way as to expose a minimum metal surface area. Hole
      formation is likely driven by the lattice mismatch of the film and the rhodium
      substrate. This regular nanostructure is thermally very stable and can serve as a
      template to organize molecules, as is exemplified by the decoration of the mesh
      by C60 molecules.

PMID- 14716011
TI  - Periodic pulsing of characteristic microearthquakes on the San Andreas fault.
AB  - Deep fault slip information from characteristically repeating microearthquakes
      reveals previously unrecognized patterns of extensive, large-amplitude, long
      duration, quasiperiodic repetition of aseismic events along much of a 175
      kilometer segment of the central San Andreas fault. Pulsing occurs both in
      conjunction with and independent of transient slip from larger earthquakes. It
      extends to depths of approximately 10 to 11 kilometers but may be deeper, and it
      may be related to similar phenomena occurring in subduction zones. Over much of
      the study area, pulse onset periods also show a higher probability of larger
      earthquakes, which may provide useful information for earthquake forecasting.

PMID- 14716012
TI  - Effects of purifying and adaptive selection on regional variation in human mtDNA.
AB  - A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences
      permitted positioning of all nucleotide substitutions according to their order of
      occurrence. The relative frequency and amino acid conservation of internal branch
      replacement mutations was found to increase from tropical Africa to temperate
      Europe and arctic northeastern Siberia. Particularly highly conserved amino acid
      substitutions were found at the roots of multiple mtDNA lineages from higher
      latitudes. These same lineages correlate with increased propensity for energy
      deficiency diseases as well as longevity. Thus, specific mtDNA replacement
      mutations permitted our ancestors to adapt to more northern climates, and these
      same variants are influencing our health today.

PMID- 14716013
TI  - Global assessment of organic contaminants in farmed salmon.
AB  - The annual global production of farmed salmon has increased by a factor of 40
      during the past two decades. Salmon from farms in northern Europe, North America,
      and Chile are now available widely year-round at relatively low prices. Salmon
      farms have been criticized for their ecological effects, but the potential human
      health risks of farmed salmon consumption have not been examined rigorously.
      Having analyzed over 2 metric tons of farmed and wild salmon from around the
      world for organochlorine contaminants, we show that concentrations of these
      contaminants are significantly higher in farmed salmon than in wild. European
      raised salmon have significantly greater contaminant loads than those raised in
      North and South America, indicating the need for further investigation into the
      sources of contamination. Risk analysis indicates that consumption of farmed
      Atlantic salmon may pose health risks that detract from the beneficial effects of
      fish consumption.

PMID- 14716014
TI  - Regulation of bone mass in mice by the lipoxygenase gene Alox15.
AB  - The development of osteoporosis involves the interaction of multiple
      environmental and genetic factors. Through combined genetic and genomic
      approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of
      peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout
      mice confirmed that 12/15-lipoxygenase plays a role in skeletal development.
      Pharmacologic inhibitors of this enzyme improved bone density and strength in two
      rodent models of osteoporosis. These results suggest that drugs targeting the
      12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis.

PMID- 14716015
TI  - Neural systems underlying the suppression of unwanted memories.
AB  - Over a century ago, Freud proposed that unwanted memories can be excluded from
      awareness, a process called repression. It is unknown, however, how repression
      occurs in the brain. We used functional magnetic resonance imaging to identify
      the neural systems involved in keeping unwanted memories out of awareness.
      Controlling unwanted memories was associated with increased dorsolateral
      prefrontal activation, reduced hippocampal activation, and impaired retention of
      those memories. Both prefrontal cortical and right hippocampal activations
      predicted the magnitude of forgetting. These results confirm the existence of an
      active forgetting process and establish a neurobiological model for guiding
      inquiry into motivated forgetting.

PMID- 14716016
TI  - Reflectins: the unusual proteins of squid reflective tissues.
AB  - A family of unusual proteins is deposited in flat, structural platelets in
      reflective tissues of the squid Euprymna scolopes. These proteins, which we have
      named reflectins, are encoded by at least six genes in three subfamilies and have
      no reported homologs outside of squids. Reflectins possess five repeating
      domains, which are highly conserved among members of the family. The proteins
      have a very unusual composition, with four relatively rare residues (tyrosine,
      methionine, arginine, and tryptophan) comprising approximately 57% of a
      reflectin, and several common residues (alanine, isoleucine, leucine, and lysine)
      occurring in none of the family members. These protein-based reflectors in squids
      provide a marked example of nanofabrication in animal systems.

PMID- 14716017
TI  - Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting.
AB  - The imprinted regulation of H19 and Insulin-like growth factor 2 expression
      involves binding of the vertebrate insulator protein, CCCTC binding factor
      (CTCF), to the maternally hypomethylated differentially methylated domain (DMD).
      How this hypomethylated state is maintained during oogenesis and the role of
      CTCF, if any, in this process are not understood. With the use of a transgenic
      RNA interference (RNAi)-based approach to generate oocytes with reduced amounts
      of CTCF protein, we found increased methylation of the H19 DMD and decreased
      developmental competence of CTCF-deficient oocytes. Our results suggest that CTCF
      protects the H19 DMD from de novo methylation during oocyte growth and is
      required for normal preimplantation development.

PMID- 14716018
TI  - RNA branching and debranching in the yeast retrovirus-like element Ty1.
AB  - Ty elements of Saccharomyces cerevisiae are long terminal repeat (LTR)
      retroelements related to retroviruses. Normal levels of Ty1 transposition require
      Dbr1p, a cellular enzyme that cleaves 2'-5' RNA bonds. We show that Ty1 RNAs
      lacking identifiable 5' ends accumulate in virus-like particles (VLPs) in dbr1
      mutants. Debranching this RNA in vitro with Dbr1p creates an uncapped version of
      the normal Ty1 RNA 5' end. We show that the 5' nucleotide (nt) of Ty1 RNA forms a
      2'-5' bond with a nt near the 3' end of the same RNA, creating a lariat. The
      properties of the lariat suggest it forms by a novel mechanism and that branching
      and debranching may play roles in Ty1 reverse transcription at the minus-strand
      transfer step.

PMID- 14716019
TI  - RAD51C is required for Holliday junction processing in mammalian cells.
AB  - During genetic recombination and the recombinational repair of chromosome breaks,
      DNA molecules become linked at points of strand exchange. Branch migration and
      resolution of these crossovers, or Holliday junctions (HJs), complete the
      recombination process. Here, we show that extracts from cells carrying mutations
      in the recombination/repair genes RAD51C or XRCC3 have reduced levels of HJ
      resolvase activity. Moreover, depletion of RAD51C from fractionated human
      extracts caused a loss of branch migration and resolution activity, but these
      functions were restored by complementation with a variety of RAD51 paralog
      complexes containing RAD51C. We conclude that the RAD51 paralogs are involved in
      HJ processing in human cells.

PMID- 14716020
TI  - Instructive role of Wnt/beta-catenin in sensory fate specification in neural
      crest stem cells.
AB  - Wnt signaling has recently emerged as a key factor in controlling stem cell
      expansion. In contrast, we show here that Wnt/beta-catenin signal activation in
      emigrating neural crest stem cells (NCSCs) has little effect on the population
      size and instead regulates fate decisions. Sustained beta-catenin activity in
      neural crest cells promotes the formation of sensory neural cells in vivo at the
      expense of virtually all other neural crest derivatives. Moreover, Wnt1 is able
      to instruct early NCSCs (eNCSCs) to adopt a sensory neuronal fate in a beta
      catenin-dependent manner. Thus, the role of Wnt/beta-catenin in stem cells is
      cell-type dependent.

PMID- 14716021
TI  - Cdh1-APC controls axonal growth and patterning in the mammalian brain.
AB  - The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons,
      but its function in the nervous system was previously unknown. We report that the
      inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth.
      Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat
      cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific
      growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA
      interference in neurons was also found to override the inhibitory influence of
      myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating
      axonal growth and patterning in the developing brain that may also limit the
      growth of injured axons in the adult brain.

PMID- 14716022
TI  - A double-pulsar system: a rare laboratory for relativistic gravity and plasma
      physics.
AB  - The clocklike properties of pulsars moving in the gravitational fields of their
      unseen neutron-star companions have allowed unique tests of general relativity
      and provided evidence for gravitational radiation. We report here the detection
      of the 2.8-second pulsar J0737-3039B as the companion to the 23-millisecond
      pulsar J0737-3039A in a highly relativistic double neutron star system, allowing
      unprecedented tests of fundamental gravitational physics. We observed a short
      eclipse of J0737-3039A by J0737-3039B and orbital modulation of the flux density
      and the pulse shape of J0737-3039B, probably because of the influence of J0737
      3039A's energy flux on its magnetosphere. These effects will allow us to probe
      magneto-ionic properties of a pulsar magnetosphere.

PMID- 14716023
TI  - Mechanisms of Abeta clearance and catabolism.
AB  - Mutations that result in an increased generation of amyloid beta peptide (Abeta)
      account for less than 5% of Alzheimer's disease (AD). Data suggesting that late
      onset AD risk factors play a role in Abeta turnover in the brain have shifted
      some of the research focus to the study of Abeta clearance and degradation and
      the impact of these processes on the etiology of Alzheimer's disease (AD). This
      review will examine the data obtained from studies performed in knockout and
      transgenic mice on the proteases; the cells and the physiological mechanisms that
      play a part in the removal of Abeta from the brain.

PMID- 14716024
TI  - Impact of aging: sporadic, and genetic risk factors on vulnerability to apoptosis
      in Alzheimer's disease.
AB  - The identification of specific genetic (presenilin-1 [PS1] and amyloid precursor
      protein [APP] mutations) and environmental factors responsible for Alzheimer's
      disease (AD) has revealed evidence for a shared pathway of neuronal death.
      Moreover, AD-specific cell defects may be observed in many other nonneuronal
      cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in
      which to study risk factors of sporadic, as well as genetic AD in vivo. The aim
      of our present study was to clarify whether lymphocytes bearing genetic or
      sporadic risk factors of AD share an increased susceptibility to cell death.
      Additionally we examined whether a cell typespecific vulnerability pattern was
      present and how normal aging, the main risk factor of sporadic AD, contributes to
      changes in susceptibility to cell death. Here, we report that lymphocytes
      affected by sporadic or genetic APP and PS1 AD risk factors share an increased
      vulnerability to cell death and exhibit a similar cell type-specific pattern,
      given that enhanced vulnerability was most strongly developed in the CD4+ T-cell
      subtype. In this paradigm, sporadic risk factors revealed the highest impact on
      cell type-specific sensitivity of CD4+ T cells to apoptosis. In contrast, normal
      aging results in an increased susceptibility to apoptosis of both, CD4+ and CD8+
      T cells.

PMID- 14716025
TI  - Interactive effects of excitotoxic injury and dietary restriction on microgliosis
      and neurogenesis in the hippocampus of adult mice.
AB  - Responses to neuronal degeneration are complex, involving activation of
      microglia, astrocytes, and synaptic remodeling. It has also been suggested that
      neuronal injury stimulates neurogenesis, the production of new neurons from
      neural stem cells. Because dietary restriction (DR) can increase hippocampal
      neurogenesis and promotes the survival of neurons following injury, we determined
      the effects of DR on the responses of neural stem cells, microglia, and
      astrocytes in the hippocampus to seizure-induced hippocampal damage. Mice on ad
      libitum or DR diets were given an intrahippocampal injection of kainate,
      administered the DNA precursor bromodeoxyuridine (BrdU) during a 5-d period, and
      euthanized 1 d or 3 wk later. Although kainate greatly increased the numbers of
      BrdU-labeled cells, it did not enhance neurogenesis and damaged neurons were not
      replaced. Instead, most BrdU-labeled cells were either proliferating microglia or
      neural progenitor cells that subsequently died. Microgliosis was transient and
      was strongly correlated with the amount of damage to CA3 neurons, whereas
      astrocytosis was delayed and not correlated with neuronal loss. Surprisingly,
      neurogenesis was not increased in response to seizure-induced damage, and
      although DR increased basal neurogenesis, it did not promote neurogenesis
      following brain injury. DR significantly decreased seizure-induced microgliosis,
      but did not affect astrocytosis. Our findings show that DR suppresses
      injuryinduced microgliosis suggesting a contribution of a reduced microglial
      response to the neuroprotective effects of DR.

PMID- 14716026
TI  - Folate and vitamin E deficiency impair cognitive performance in mice subjected to
      oxidative stress: differential impact on normal mice and mice lacking
      apolipoprotein E.
AB  - One factor contributing to the age-related decline in cognitive performance is
      increased oxidative stress, that can arise from environmental, nutritional,
      and/or genetic compromise. Folate deficiency has been linked to several age
      related neurodegenerative conditions, including Alzheimer's disease (AD), at
      least in part by increasing oxidative stress. Folate deficiency also potentiates
      the impact of other known risk factors for AD. Adecrease in function of
      apolipoprotein E (ApoE), is associated with increased oxidative stress and is a
      risk factor for AD. We tested the combined impact of dietary deficiencies in
      folate and vitamin E, coupled with exposure to high dietary iron as a pro
      oxidant, on cognitive performance in normal and ApoE-/- mice by monitoring the
      percent alternation in passive Y and T maze tests. Both normal and ApoE-/- mice
      displayed some cognitive impairment when deprived of folate and vitamin E and
      exposed to iron, but ApoE-/- mice were more severely affected. These findings
      highlight the potential combined impact of dietary deficiencies and genetic
      predisposition to neurodegeneration. They further leave open the possibility that
      one or more risk factors may remain latent, and neurodegeneration may ensue only
      following augmentation by one or more additional traumatic events or conditions.

PMID- 14716027
TI  - Flt3 in acute myelogenous leukemia: biology, prognosis, and therapeutic
      implications.
AB  - Flt3 is a tyrosine kinase receptor expressed on hematopoietic cells. Activating
      mutations of this receptor are encountered in over one-fourth of acute
      myelogenous leukemia (AML) cases and activate multiple intracellular pathways
      leading to cell proliferation, inhibition of apoptosis, and blockage of
      differentiation in leukemic blasts. AML with flt3 mutations has a worse prognosis
      than AML with normal flt3, at least in younger patients. Several flt3 inhibitors
      are in various stages of preclinical and clinical development and it is hoped
      that specific therapies against AML with flt3 mutations will soon be available to
      the clinician.

PMID- 14716029
TI  - Cytoplasmic expression of EGFP in dendritic cells transfected with in vitro
      transcribed mRNA or cellular total RNA extracted from EGFP expressing leukemia
      cells.
AB  - The present study was designed for identifying the protein synthesis in cytoplasm
      of dendritic cells transfected with in vitro transcribed mRNA and cellular total
      RNA extracted from tumor cells. Dendritic cells were generated from cord blood
      CD34+ cells by culture with GM-CSF, SCF, and TNF-alpha, or from peripheral blood
      adherent cells or CD14+ cells by culture with GM-CSF and IL-4. Dendritic cells
      were transfected with in vitro transcribed EGFP mRNA or cellular total RNA, which
      was isolated from EGFP expressing K562, by electroporation using a square-wave
      pulse. Optimal in vitro transcribed EGFP mRNA transfection efficiency (>90%) was
      observed in a single electroporation of 1.75 kV/cm (electric field strength) with
      a pulse width of 250 micros. Although the intensity of EGFP expression in
      dendritic cells transfected with cellular total RNA was less compared with that
      in dendritic cells transfected with in vitro transcribed EGFP mRNA, a definite
      cytoplasmic synthesis of EGFP was demonstrated in dendritic cells transfected
      with cellular total RNA. The visual identification of cytoplasmic expression of
      cellular total RNA in dendritic cells revealed that electroporation of tumor cell
      derived RNA could be a useful tool to load dendritic cells with tumor antigens
      for establishing an efficient dendritic cell-based tumor immunotherapy.

PMID- 14716028
TI  - Prognostic factors of immunotherapy in metastatic renal cell carcinoma.
AB  - The prognosis of the majority of patients with metastatic renal cell carcinoma is
      poor, and there is no internationally recognized standard therapy for these
      patients. Patients are treated with interferon alpha or interleukin- 2
      monotherapy, or combinations outside of clinical trials and a subgroup of
      patients responds to these therapies. Because immunotherapy induces adverse
      effects in almost every patient, it is necessary to avoid treating patients who
      will not, in the end, benefit from the treatment. It is therefore sensible to
      carefully select patients prior to the initiation of immunotherapy. Determining
      prognostic factors of survival or of rapid progression under treatment would be
      of help for selecting patients for immunotherapy. This article reviews current
      data about prognostic and predictive factors from immunotherapy studies in
      metastatic renal cell carcinoma comparing all analyzed factors with those that
      demonstrated an independent prognostic significance in multivariate analyses.

PMID- 14716030
TI  - Skeletal trauma preceding the development of plasma cell dyscrasia: eight case
      reports and review of the literature.
AB  - Plasma cell dyscrasias are clonal proliferations and accumulations of plasma
      cells. The etiology of monoclonal neoplasms still remains elusive. A direct
      correlation between a history of trauma and the development of plasma cell
      dyscrasias has not been established. Two recent case reports have described
      plasmacytomas that were diagnosed in patients who suffered injury at the site of
      plasma cell neoplasms. We report a series of eight patients who stated a history
      of trauma to the site where plasma cell neoplasms were later diagnosed. The
      duration from the date of injury to diagnosis ranged from 2 mo to 20 yr. The M:F
      ratio was 6:2. The median age was 52 (28-75). Multiple myeloma was confirmed in
      six patients and plasmacytoma without systemic disease in the other two patients.
      All eight patients had a kappa monoclonal plasma cell population, and all but one
      had a detectable peripheral kappa light chain. All patients presented with
      persistent discomfort at the site where they had experienced trauma. Even though
      this article does not establish a relationship between trauma, and the
      development of plasma cell dyscrasia, persistent discomfort at a previous trauma
      site warrants a complete evaluation and consideration for possible plasma cell
      dyscrasias.

PMID- 14716031
TI  - Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to
      gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer.
AB  - The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through
      induction of apoptosis. To examine whether the efficacy of GC chemotherapy might
      be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor,
      we investigated the correlation between the tumor response rate and DR5 and Bcl-2
      expression in a series of patients prospectively treated with GC. Thirty-four
      chemotherapy naive patients with advanced non-small-cell lung cancer (NSCLC)
      received intravenously 1000 mg/m2 gemcitabine on d 1 and 8 along with 80 mg/m2
      cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2
      expression by immunohistochemistry. The objective response rate was 56% (19 of 34
      patients). With median follow-up of 10 mo, the predicted median survival time was
      12 mo (95% confidence interval [CI], 9-15 mo). Eleven (32%) and 14 (41%) NSCLC
      cases were found positive for DR5 and Bcl-2, respectively. The response rate was
      significantly higher in patients with DR5 expression than those without DR5
      expression (91% vs 39%; p = 0.008). Patients with Bcl-2 expression were
      apparently less responsive than those without Bcl-2 expression (21% vs 80%; p =
      0.001). DR5 and Bcl-2 expression was significantly associated with response to GC
      chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting
      the efficacy of GC.

PMID- 14716032
TI  - Actual body weight for determining doses of chemotherapy in obese cancer
      patients: evaluation of treatment tolerability.
AB  - In our Department, doses of chemotherapy in obese cancer patients are routinely
      calculated according to actual body weight. As some physicians question this
      policy, we prospectively evaluated the safety of this approach. Of 606
      consecutive patients, 178 (29%) were obese, defined as body mass index > or =27.3
      kg/m2 for females and > or =27.8 kg/m2 for males; full-dose chemotherapy was
      initiated in 147 (24%). Severe chemotherapy- related toxicity (SCRT) (neutropenic
      fever, severe thrombocytopenia associated with significant bleeding and/or
      requiring platelet transfusion, or grade 3-4 nonhematologic toxicity other than
      alopecia, nausea, and vomiting) during the first three cycles was evaluated. SCRT
      was noted in 16/147 (11%) during the first cycle, 10/146 (7%) during the second
      cycle, and 6/142 (4%) during the third cycle. Drug doses were reduced due to
      toxicity in 15/146 (10%) during the second cycle and 11/142 (8%) during the third
      cycle. There were no treatment- related deaths. It was concluded that calculation
      of standard chemotherapy dose according to actual body weight in obese patients
      is relatively safe.

PMID- 14716033
TI  - Risk-awareness of cutaneous malignancies among rural populations.
AB  - The prevention of skin cancer relies not only on the knowledge of the risks of
      ultraviolet rays, but also on the appropriate measures to minimize solar
      exposure. We conducted a questionnaire-based survey among a rural population to
      evaluate perceptions regarding (i) sun-related behaviors, (ii) measures taken to
      protect themselves, and (iii) self-skin assessment knowledge. Questions included
      data on patients' knowledge of deleterious effects of sun exposure, their habits
      and perceptions about adequate protection, their knowledge of a suspicious
      cutaneous lesion, and if a physician had spoken to them about the risks of
      ultraviolet/solar exposure. One hundred and six adults (38 males and 68 females)
      seen in a primary care clinic were enrolled in our study. Of these, only 38.7% of
      our patients were concerned about their risk of cutaneous malignancies. On
      analysis of the sun-protection variables, we found an increased use of tanning
      beds among women and an increased use of hats in men. Interestingly, we also
      found that only 18% of respondents used sunscreen when anticipating sun exposure.
      With suspicious skin lesions, color of the lesion appeared to be the most
      concerning factor for the subjects, with increasing size being the second most
      likely factor of concern. Only 11.3% of respondents had a physician-performed
      skin assessment and only 19.8% performed self-skin assessments at least yearly.
      There seems to be a lack of appropriate knowledge regarding precancerous and
      cancerous skin lesions among rural communities. Increased patient education is
      urgently necessary in rural populations to decrease the growing incidence of
      cutaneous malignancies.

PMID- 14716034
TI  - Hairy cell leukemia in father and son.
AB  - Hairy cell leukemia (HCL) is an uncommon B cell disorder, and familial HCL is
      rarely encountered among the first degree relatives of HCL patients. A father and
      son, both of whom developed hairy cell leukemia, is presented in this report. The
      HLA haplotype shared by the father and son was A2, B18, BW6, CW7, DR3, DR10, and
      DQ8. Among these haplotypes, HLA A2 and Bw6 have previously been reported.

PMID- 14716035
TI  - Probable veno-occlusive disease after treatment with gemtuzumab ozogamicin in a
      patient with acute myeloid leukemia and a history of liver transplantation for
      familial hemochromatosis.
AB  - A 69-yr-old male with a history of familial hemochromatosis and status after
      liver transplantation was found to have severe thrombocytopenia (platelet count
      of 8000/microL). He was also anemic and was diagnosed with acute myeloid leukemia
      (AML) after a bone marrow biopsy. He was started on gemtuzumab ozogamicin
      (Mylotarg) and developed hepatic and multiorgan failure consistent with veno
      occlusive disease within 2 wk. He did not have a history of hematopoietic stem
      cell transplantation, which is usually the case in AML patients who develop veno
      occlusive disease of the liver after treatment with Mylotarg.

PMID- 14716036
TI  - Gemcitabine and reactivation of hepatitis B.
AB  - Patients with chronic hepatitis B are at risk of reactivation of viral hepatitis
      during chemotherapy. We report a case of hepatitis B reactivation occurring in
      association with single-agent gemcitabine chemotherapy in the absence of
      significant myelosuppression. Gemcitabine is a nucleoside analog that can affect
      cell-mediated immunity, and this may contribute to an increased risk of
      reactivation of hepatitis B. We advise caution when administering chemotherapy to
      patients who are hepatitis B surface antigen positive, even when using relatively
      nontoxic palliative single-agent cytotoxic drugs. Monitoring of liver function
      tests will identify hepatitis, and measurement of hepatitis B DNA levels may help
      distinguish chemotherapy-induced hepatitis from hepatitis B virus reactivation.

PMID- 14716038
TI  - Angiosarcoma of the small intestine: a possible role for thalidomide?
AB  - An 85-yr-old male presented with complaints of a 40-lb weight loss and a dull
      left upper quadrant abdominal pain. He also complained of decreased appetite,
      generalized weakness, generally not feeling well, and a dull left upper quadrant
      abdominal pain that was not relieved by food. He had a ventral and a left-sided
      inguinal hernia. Laboratory investigations revealed iron deficiency anemia, the
      cause of which was not apparent despite extensive investigation including
      computerized tomographic scans, esophagogastroduodenoscopy, and small-bowel
      follow-through examination. Surgical exploration for possible angiodysplasia,
      malignancy, and/or mesenteric ischemia revealed an incarcerated hernia, and the
      histopathological examination of the surgical specimen revealed high-grade
      angiosarcoma. The tumor showed strong positivity for vimentin and CD31 and a
      focal positivity for Factor VIII and CD34. At that time he was found to have
      hepatic metastases. He was started on thalidomide as an experimental measure with
      no change in the performance status and increasing evidence of necrosis in the
      metastatic lesion.

PMID- 14716037
TI  - Mycosis fungoides/Sezary syndrome: a report of three cases treated with Campath
      1H as salvage treatment.
AB  - We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three
      patients with advanced mycosis fungoides/Sezary syndrome who had previously been
      treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42
      and 68 yr, respectively, were heavily pretreated (more than three prior therapy
      regimens, including autologous transplant in case 2) and refractory to
      conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had
      refused any chemotherapy, had been resistant to treatment with cyclosporine and
      steroids. Campath-1H was administered intravenously, after an escalating dose
      from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of
      1080, 223, and 480 mg, respectively. The patients with Sezary syndrome (case 2
      and case 3) showed clearance of circulating Sezary cells and clinical improvement
      of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3)
      completed the treatment (12 and 6 wk) without significant toxicity, the former
      achieving a partial response and the latter a clinical complete response. The
      patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly
      achieved a clinical improvement of the Sezary syndrome, but he died because of a
      myocardial infarction after 3 wk of treatment. Our report shows that the
      treatment with Campath-1H is active even in patients with advanced refractory
      mycosis fungoides/Sezary syndrome. Further clinical observations on a larger
      cohort of patients are needed to establish if Campath-1H may have a role as first
      line therapy in addition to conventional therapy including chemotherapy.

PMID- 14716039
TI  - Doege-Potter syndrome: hypoglycemia associated with malignant solitary fibrous
      tumor.
AB  - We report a case of recurrent solitary fibrous tumor with associated
      hypoglycemia, the "Doege-Potter syndrome." These are rare tumors with a 12-13%
      rate of malignancy. The syndrome of hypoglycemia is seen in less than 5% of the
      cases, and the associated tumors are large with a high mitotic rate. The cause of
      hypoglycemia is related to insulin-like growth factors produced by these tumors.
      Resection in many cases is curable with resolution of the hypoglycemia. We
      discuss the different signs and symptoms and literature evidence of treatment
      options and follow-up.

PMID- 14716040
TI  - ALK-negative T-cell anaplastic large cell lymphoma associated with systemic lupus
      erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) appear to have an increased risk
      of developing malignancies, especially lymphomas. We report the development of a
      systemic ALK-negative T-cell anaplastic large cell lymphoma, stage IIB, in a 53
      yr-old Caucasian female with a 12-yr history of stable SLE. The patient responded
      poorly to chemotherapy and died 2 yr after diagnosis. Lymphomas that develop in
      patients with SLE and other autoimmune diseases are virtually always of B-cell
      origin. To our knowledge this is the first report of a T-cell anaplastic large
      cell lymphoma in a patient with SLE. This article discusses the association of
      SLE and lymphoma, with an emphasis on T-lymphoproliferative states.

PMID- 14716041
TI  - Primary non-Hodgkin's lymphoma of the transverse colon presenting as
      dermatomyositis: case presentation and literature review.
AB  - Primary extranodal non-Hodgkin's lymphoma of the transverse colon is a rare
      presentation of non-Hodgkin's lymphoma or colonic neoplasm. Dermatomyositis is an
      autoimmune condition of the skin, muscle, and blood vessels that when associated
      with malignancy is a true paraneoplastic syndrome but is rarely associated with
      non-Hodgkin's lymphoma. We present a case of primary non-Hodgkin's lymphoma of
      the transverse colon diagnosed after the presentation of dermatomyositis and
      review the literature on dermatomyositis and hematologic neoplasm.

PMID- 14716042
TI  - Nonresponders to osteoporosis therapy.
AB  - The goal of osteoporosis therapy is reduction of fracture risk. In randomized
      controlled trials, relative risk of fracture is determined by comparing the
      absolute fracture rate of a treatment group to a control group. Fracture risk
      cannot be measured in individual patients being treated for osteoporosis. Since
      osteoporosis is a silent disease, and some patients may not respond to therapy, a
      surrogate test for reduction of fracture risk is often used-most commonly a bone
      density test. A proposed definition of nonresponse is: A decrease in bone mineral
      density greater than the Least Significant Change at the 95% level of confidence.
      The Least Significant Change is a value based on bone density measurements in
      patients and calculated according to well-established standards. There are other
      candidates for measuring responsiveness to therapy, most notably biochemical
      markers of bone metabolism, but none is as well validated or standardized as bone
      density testing. Causes of nonresponse include poor adherence, co-morbid
      conditions, calcium and vitamin D deficiency, malabsorption, metabolic factors,
      wrong dose, wrong dosing interval, and lack of efficacy. A bone density increase
      or stability of bone density is associated with fracture risk reduction in
      approved osteoporosis therapies, while a bone density decrease is cause for
      clinical concern. The proposed definition of nonresponse identifies a subset of
      patients who may require a change of therapy and/or additional medical
      intervention. More data are needed to develop guidelines for clinicians. Further
      study is suggested.

PMID- 14716043
TI  - What predicts early fracture or bone loss on bisphosphonate therapy?
AB  - Factors predicting early fracture or bone loss on bisphosphonate therapy are not
      well defined. We studied 1588 patients over the age of 50 yr who were started on
      cyclic etidronate (1119) or alendronate (469) in the CANDOO (Canadian Database
      for Osteoporosis and Osteopenia Patients) Study. Incident fracture within 2 yr of
      starting therapy occurred in 31 patients and was independently predicted by a
      previous history of nonvertebral fracture (odds ratio [OR], 2.98, 95% confidence
      interval [CI], 1.30, 6.83, p = 0.010). Two hundred and fifty-seven patients lost
      >/=3% bone mass at the hip or spine (early bone loss) while on bisphosphonate
      therapy. Protection from early bone loss was most strongly independently
      predicted by treatment with alendronate with no previous history of etidronate
      use (OR, 0.29, CI, 0.13, 0.62, p = 0.002). In conclusion, early fracture on
      bisphosphonate therapy is most strongly predicted by a previous history of
      fracture and early bone loss is most strongly predicted by the potency of the
      prescribed bisphosphonate.

PMID- 14716044
TI  - Does bone mineral density and knowledge influence health-related behaviors of
      elderly men at risk for osteoporosis?
AB  - To determine if bone mineral density (BMD) substantially influences health
      related behaviors in men at risk for osteoporosis, we surveyed 102 men who were
      participating in a study of prostate cancer and bone loss. Subjects included 68
      men with prostate cancer, 44 of whom were hypogonadal on androgen deprivation
      therapy, and 34 healthy age-matched controls without prostate cancer. At least 6
      mo after an initial evaluation, assessment of BMD, and osteoporosis information
      session, men were administered a questionnaire regarding their healthrelated
      behaviors. We found that men with osteopenia were 4 times as likely (13%) and men
      with osteoporosis were more than 10 times as likely (41%) to start taking
      bisphosphonates compared to men with a normal bone mass (3%, p < 0.0001). Men
      with low bone mass were more likely to begin taking calcium (p < 0.05) and
      vitamin D supplements (p < 0.05). Hypogonadal men were 10 times as likely to
      begin using bisphosphonates (34%) compared to the control group (3%, p < 0.0001)
      and twice as likely to begin using calcium supplements (57% vs 24%, p < 0.05).
      Caffeine consumption, alcohol consumption, dietary calcium intake, exercise, and
      smoking habits were not different in men with osteoporosis or those who were
      hypogonadal compared to controls. We conclude that men with low bone mass and
      hypogonadism were more likely to start using bisphosphonates, calcium
      supplements, and vitamin D supplements after having a bone density test. However,
      they were not more likely to make significant health-related lifestyle changes
      after obtaining the results of their bone mass.

PMID- 14716045
TI  - Effect of leg rotation on hip bone mineral density measurements.
AB  - Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is
      widely used in the management of patients with osteoporosis. Factors, which are
      specific to machine or to operator, can influence the accuracy and precision of
      BMD estimations. We studied the effect of leg rotation by 10 degrees either
      internally or externally from the standard position in a group of 50 women
      (average age 54.9, SD = 11.1 yr) who were free of bone active diseases or
      medications. External rotation of leg by 10 degrees from the customary position
      increased the average BMD by 0.005, 0.003, and 0.036 g/cm2 in the femoral neck,
      trochanter, and Ward's area (p = 0.119, 0.309, and <0.001), respectively.
      Internal rotation of leg by 10 degrees from the customary position decreased the
      average BMD by 0.009, 0.005, and 0.006 g/cm2 in the femoral neck, trochanter, and
      Ward's area (p = <0.001, 0.008, and <0.001), respectively. The number of subjects
      qualified for the diagnosis of osteoporosis based on the T-scores (equal to or
      below -2.5) of the femoral neck and trochanter did not change significantly in
      three different positions (18% in the customary position and after the external
      rotation and 14% after the internal rotation). A significant change in the
      femoral neck BMD (defined as 2.77 x precision error) was seen in 12% of subjects
      after the internal rotation and 8% after the external rotation. Our data
      emphasize the need for proper positioning of the hip during DXA scanning.
      Malrotation of the hip can be an important confounding factor when interpreting
      serial BMD values.

PMID- 14716046
TI  - Reproducibility and concordance in quantitative ultrasound measurements between
      densitometers: a comparative study.
AB  - Although calcaneal quantitative ultrasound (QUS) is an independent predictor of
      osteoporotic fracture, its role in monitoring changes in bone status remains
      limited because of its relatively poor precision compared to the rate of bone
      loss. Recently, imaging QUS has been developed that can standardize the region of
      interest in the calcaneus with the potential of improving precision. We assessed
      the concordance and precision of an imaging QUS scanner (UBIS 5000) and a
      nonimaging scanner (LUNAR Achilles+) in 52 subjects aged between 27 and 79 yr.
      Each subject had duplicate measurements on each scanner on the same day. The
      measurements were broad-band ultrasound attenuation (BUA), speed of sound (SOS),
      and stiffness index, which was derived from BUA and SOS. Precision was evaluated
      by the standard error of measurement (SEM) and within-subject coefficient of
      variation (CV). There was significant correlation between the two scanners in all
      QUS measurements (r > 0.8; p < 0.001); however, BUA and SOS measurements by the
      UBIS were significantly lower than by the Achilles+. The SEM of BUA (0.6 dB/MHz)
      and SOS (2.7 m/s) in the UBIS were significantly lower (p < 0.001) than the
      Achilles+ (1.4 dB/MHz for BUA and 6.3 m/s for SOS). When the SEM was expressed as
      the percentage of the mean, there were no significant differences in CVs between
      UBIS (0.9% for BUA and 0.2% for SOS) and Achilles+ (1.2% for BUA and 0.4% for
      SOS) scanners. The SEM of stiffness index derived by UBIS was not significantly
      different from that derived by the Achilles+. These data suggest that although
      there are systematic differences between the UBIS and Achilles+ scanners in QUS
      measurements, the precision of the two instruments is equivalent.

PMID- 14716047
TI  - A comparison of calcaneal dual-energy X-ray absorptiometry and calcaneal
      ultrasound for predicting the diagnosis of osteoporosis from hip and spine bone
      densitometry.
AB  - Peripheral densitometry is increasingly being used in the management of
      osteoporosis, but the optimal diagnostic thresholds have not been defined. The
      aim of this study was to determine the optimal T-score for peripheral dual-energy
      X-ray absorptiometry (pDXA) of the heel using a GE Lunar PIXI and quantitative
      ultrasound (QUS) of the heel using a GE Lunar Achilles Plus when compared with
      dual-energy X-ray absorptiometry (DXA) of central sites (spine, femoral neck, or
      total hip). Ninety-nine women (mean age 69 +/- 8, range 33-86 yr) referred from
      the metabolic bone clinic were studied. The optimal T-score for pDXA from ROC
      analysis was -1.7 and for QUS was -2.5. The pDXA T-score that defined the same
      prevalence of osteoporosis at any central site was also -1.7 and for QUS was 
      2.4. These results are similar to the manufacturer's recommendations. There is no
      significant difference in performance between the PIXI and QUS.

PMID- 14716048
TI  - Improving femoral bone density measurements.
AB  - Femoral bone density measurements are clinically important because of their
      strong relationship with hip fracture. However, current densitometers have not
      improved upon femoral densitometry since the introduction of dual-energy X-ray
      absorptiometry (DXA) systems. Recently, several advances in DXA measurement of
      the proximal femur have been proposed by various published studies. These
      advances can be added to existing DXA systems, while maintaining the conventional
      femoral regions of interest. Both upper neck bone mineral density (BMD) and hip
      axis length have been reported to be associated with hip fractures. With newer
      technology that enables a rapid assessment of both hips, bilateral femur
      measurements are now clinically practical and are of importance in those with T
      scores approaching, yet not reaching, diagnostic or therapeutic thresholds.
      Bilateral femur measurements also reduce precision error compared to a single
      femur measurement, yielding precision errors less than observed at the spine.
      With this decrease in precision error, monitoring of bone changes is now possible
      at the femur with the utility comparable to the spine.

PMID- 14716049
TI  - Vertebral morphometric X-ray absorptiometry in women with Colles' fracture.
AB  - Colles' fracture (CF) in younger postmenopausal women is associated with low bone
      mineral density (BMD) and with an increased risk of other osteoporotic fractures;
      however, the prevalence of vertebral deformities has been not studied in CF
      patients. Vertebral morphometry (MXA) using dual-energy X-ray absorptiometry
      (DXA) is a research tool developed to evaluate the presence of vertebral
      deformities, but its clinical use is still limited. The goals of this work were
      to know the prevalence of vertebral deformities in women with CF, to study the
      morphometric characteristics of height ratios, and to determine the correlation
      between MXA findings and BMD. MXA was evaluated within an incident case-control
      study in which 58 women with a recent CF and 83 population-based control women
      were enrolled. Anterior (Ha), middle (Hm), and posterior (Hp) heights were
      measured, and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios were calculated. A
      vertebral deformity was defined when at least one ratio fell 3 SD below the
      reference mean of that ratio at any vertebral level. The mean age of cases was
      65.8 yr and in controls 58.7 (p < 0.05). Morphometric vertebral deformities were
      found in 19% of cases against 11% of controls (nonsignificant). The cases had a
      lower mid-wedge ratio than controls at each vertebral level (p < 0.05), while
      wedge ratio results did not show significant results. When the sample was
      stratified by age, CF showed a trend to be associated with vertebral deformity
      only in the younger (<65 yr) group. A low but significant coefficient of
      correlation was found between mid-wedge ratio and BMD, mainly at hip level. By
      using MXA we found that younger Colles' fracture cases were likely to have more
      vertebral deformities than healthy controls of the same age range.

PMID- 14716050
TI  - Reference database for dual X-ray and laser Calscan bone densitometer.
AB  - The new dual X-ray and laser technology (DXL) gives a more accurate determination
      of bone mineral density (BMD) than ordinary dual X-ray absorptiometry (DXA)
      technology because of the ability to eliminate fat tissue both inside and outside
      the measured bone. In this study the reference database for BMD measured at the
      calcaneus by the DXL Calscan device is reported. The database was obtained from
      993 healthy women and 459 healthy men in a population from southern Sweden.
      Inclusion criteria were: healthy Swedish Caucasians, 15-85 yr of age for women
      and 19-85 yr of age for men, no history of osteoporosis treatment, no use of
      corticosteroids for more than 3 mo, and no extended bed rest. The young adult
      reference mean BMD for women was found to be 0.483 +/- 0.062 g/cm2 and for men
      0.556 +/- 0.074 g/cm2. The age-adjusted odds ratio was 3.7 for a history of
      fracture among women aged 50 yr and over, comparing subjects with a 1-SD
      reduction in bone density to subjects with a bone density above this value. The
      DXL Calscan device used for the study was calibrated weekly against a heel bone
      phantom. The precision of these measurements was 0.5%. The in vivo precision was
      1.2%, as assessed by duplicate measurements on 35 healthy individuals (mean age
      52 yr, range 25-72 yr).

PMID- 14716051
TI  - Reference curve of bone ultrasound measurements in proximal phalanges in normal
      Spanish women.
AB  - There are clear discrepancies in how the different measurements of phalangeal
      bone ultrasound, such as the amplitude-dependent speed of bone ultrasound (Ad
      SoS), correlate with age, given their dependence on gonadal status and other
      anthropometric variables. In order to contribute to clarifying these
      discrepancies, we evaluated the phalangeal Ad-SoS in healthy women-295
      postmenopausal, 59 perimenopausal, and 270 premenopausal. Phalanges (II-V) of the
      nondominant hand were measured and the mean Ad-SoS was computed. There were
      significant differences between groups (p < 0.0001 in all cases), with the
      perimenopausal group presenting the intermediate values. For the overall group of
      women, the Ad-SoS was significantly and negatively correlated with age, weight,
      and body mass index (BMI), and positively correlated with height (p < 0.0001 in
      all cases). By gonadal status group, the premenopausal women showed the three
      significant negative correlations of Ad-SoS with age, weight, and BMI (each, p <
      0.0001), the perimenopausal group only with BMI (p < 0.007), and the
      postmenopausal group with age and BMI (p < 0.0061 to p < 0.0001) and also with
      years since menopause (p < 0.0001). The premenopausal decline in AD-SoS requires
      further longitudinal studies, although in our experience it may depend on dietary
      habits and/or a diminished quality, though not quantity, of bone in this period
      of a woman's fertile life.

PMID- 14716052
TI  - Precision and accuracy of DXA and pQCT for densitometry of the rat femur.
AB  - Measurements of bone mineral density and bone mineral content are key data in the
      study of osteoporosis and pathologic skeletal disease. Dual-energy X-ray
      absorptiometry and peripheral quantitative computed tomography are used in human
      and small animal studies. The purpose of this study was to evaluate the
      precision, accuracy, and systematic bias of measurement of the rat femur.
      Comparing machine-measured parameters with standard, nonradiographic
      measurements, we assessed validation of relative and absolute accuracy.
      Regression analysis and calculations of percent difference from standard values
      were used to determine the accuracy of each densitometry technique. Machine
      specific and subject-specific precision was evaluated for each densitometer using
      repeated scans to calculate coefficients of variation. Each of the methods of
      densitometry examined in this study produced comparable results and was sensitive
      to small changes following experimental stimuli. Further, our assessment of the
      precision and accuracy observed between methods of scanning excised rat femurs
      validates our data acquisition method and serves as a foundation for future
      densitometry studies.

PMID- 14716053
TI  - A 6-mo home-based exercise program may slow vertebral height loss.
AB  - Twenty-one of 46 postmenopausal women were assigned to a home-based exercise
      program consisting of 60 min of exercise, 3 d/wk. The 25 nonexercisers continued
      usual daily activities. Each woman had at least one prevalent vertebral fracture
      and suffered from osteoporosis as defined by the application of WHO criteria to
      lumbar spine bone mineral density. Vertebral heights were measured using bone
      densitometry at baseline and 12 mo later. Vertebrae T9 to L4 were all identified
      for each of the 46 subjects in both the baseline and end-of-study lateral scans.
      The change in mean vertebral height over the course of the study was -0.3 mm
      anteriorly, -0.7 mm at the mid-location, and -0.4 mm posteriorly for the
      nonexercisers. For the exercisers, the corresponding changes were +0.1 mm
      anteriorly, -0.3 mm at the mid-location, and +0.2 mm posteriorly. The benefit of
      exercise in preserving vertebral morphometry in patients with osteoporosis
      deserves further investigation.

PMID- 14716054
TI  - Automated assessment of exclusion criteria for DXA lumbar spine scans.
AB  - Modern bone densitometry systems using dual-energy X-ray absorptiometry (DXA)
      automatically analyze lumbar spine scans and provide clinically important
      information concerning spine bone mineral density (BMD) and fracture risk. Lumbar
      spine BMD accurately reflects skeletal health and fracture risk in most cases,
      but degenerative diseases associated with aging may lead to the formation of
      reactive bone (osteophytes) and other confounding conditions that elevate BMD
      without a concomitant increase in bone strength or decrease in fracture risk.
      Automated densitometry software known as computer-aided densitometry (CAD) (GE
      Medical Systems Lunar) assists the user in identifying scans with common
      acquisition and analysis irregularities known to influence BMD values. Visual
      examination of 231 female spine scans measured with DXA found abnormal conditions
      that could influence BMD results in 29% of scans. The sensitivity and specificity
      of several criteria for identifying scans with conditions that could influence
      BMD were determined. A good criterion for identifying scans with abnormal
      conditions was a T-score difference of greater than 0.9 or 1.0 between L1-L4 mean
      and individual vertebrae. Criteria for excluding affected vertebrae were
      determined. Exclusion of affected vertebrae resulted in a mean BMD decrease of
      nearly 0.6 SD (T-score) among affected scans.

PMID- 14716055
TI  - A calcitonin and vasoactive intestinal peptide-producing pancreatic endocrine
      tumor associated with the WDHA syndrome.
AB  - BACKGROUND: Although pancreatic endocrine tumor can produce a variety of
      hormones, few pancreatic tumors produce a high systemic calcitonin concentration.
      Furthermore, calcitonin-producing pancreatic tumors rarely produce elevations of
      VIP in addition. METHODS: We evaluated and treated a 50-yr-old woman with the
      WDHA syndrome. Abdominal computed tomography (CT) detected a tumor in the tail of
      the pancreas. Peripheral plasma calcitonin and VIP concentrations were markedly
      increased to 2000 pg/mL (normal, <74 pg/mL) and 7200 pg/mL (normal, <100 pg/mL),
      respectively. We diagnosed a calcitonin- and VIP-producing pancreatic endocrine
      tumor, which was removed by distal pancreatectomy including splenectomy. RESULTS:
      Plasma calcitonin and VIP were determined in blood from the vein draining the
      tumor and splenic vein, sampled at operation. These secreted concentrations were
      extremely high: 4640 and 3610 pg/mL for calcitonin; 24700 and 13500 pg/mL for
      VIP. Calcitonin and VIP were also highly elevated in the resected tumor. Plasma
      calcitonin and VIP rapidly decreased after tumor resection. The patient has been
      well without recurrence for over 20 yr. CONCLUSION: An unusual pancreatic tumor
      secreting vasoactive intestinal peptide (VIP) caused WDHA syndrome (watery
      diarrhea, hypokalemia, and achlorhydria/hypochlorhydria) and also hypercalcemia.
      The latter was only partially offset by a large excess of calcitonin also
      secreted by the tumor.

PMID- 14716056
TI  - Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas.
AB  - Pure undifferentiated carcinoma with osteoclast-like giant cells of the pancreas
      is very rare. Its prognosis is grim. The clinicopathologic findings of a case of
      this unusual tumor are presented. Following resection, the patient at 9 mo follow
      up developed local recurrence.

PMID- 14716057
TI  - Long-term survival after radical resection of advanced pancreatic cancer: a case
      report with special reference to CD8+ T-cell infiltration.
AB  - A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection
      for pancreatic cancer is alive 8 yr after surgery. Originally, computed
      tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had
      infiltrated the portal vein, but grew expansively, so there was neither biliary
      obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal
      vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes
      were seen within cancer cell nests on routine histopathology. We performed
      immunostaining for CD8, and found that a large number of the lymphocytes were
      CD8+ T cells. The patient's prognosis was considered poor because the tumor was
      large and had infiltrated the portal vein. We suspect that long-term survival may
      be related to the response of CD8+ T cells to the cancer.

PMID- 14716058
TI  - Subcutaneous metastasis at a surgical drain site after the resection of
      pancreatic cancer.
AB  - The aggressive nature of pancreatic cancer makes surgical control of disease an
      arduous challenge. Tumor seeding during resection is a feared complication during
      operations performed for this disease. Recurrence within the peritoneal cavity
      commonly occurs after resection for curative intent. Cutaneous metastasis,
      however, is a rare event. The majority of skin metastasis reported in the
      literature occurred after palliative procedures, in which the tumor burden
      remains. In this report, we describe an unusual case of cutaneous recurrence at
      the site of a surgical drain after resection for curative intent and discuss the
      impact of surgery on tumor-growth characteristics.

PMID- 14716059
TI  - Synchronous primary carcinomas of the ampulla of Vater and ascending colon in a
      patient with multiple flat adenomas.
AB  - Multiple primary cancers occurring in the same patients have been reported to
      represent 1.8-3.9% of all cancers. The majority of all patients reported to have
      had a combination of simultaneous neoplastic changes in the ampulla of Vater and
      the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of
      familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli
      (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli.
      AAPC is characterized clinically by many, but usually fewer than 100, colonic
      lesions that are characteristically slightly elevated and plaque-like, with a
      reddish surface and sometimes central depression. Genetically it represents an
      extremely rare variant of FAP. Another group of individuals, so-called multiple
      adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable
      germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC.
      However, there have been only a few reports that discussed concurrent neoplastic
      changes in the ampulla of Vater and colon in patients with multiple colonic flat
      adenomas, but without the florid phenotype of classical FAP. We present rare
      clinical course of a patient with multiple (more than 60) flat adenomas in the
      proximal colon and two primary cancers: of the ampulla of Vater and of the
      ascending colon. This patient and his family history did not show polyposis
      compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC)
      syndrome.

PMID- 14716060
TI  - Mikulicz syndrome associated with a malignant large cell gastric lymphoma: a case
      report and review of the literature.
AB  - There is much confusion in the literature regarding the differences between
      Mikulicz disease and Mikulicz syndrome. This may be because there seems to be a
      connection between the disease and disease processes associated with the
      syndrome. This article provides historical data discussing the emergence of
      Mikulicz disease, confusions regarding its definition, and finally offers an
      explanation to the interrelationships of these two entities. This case report
      hypothesizes that the non-Hodgkin's lymphoma (NHL), which in association with
      Sjogren's syndrome and Mikulicz disease in this patient comprised the Mikulicz
      syndrome, may have transformed into his malignant large-cell gastric lymphoma. It
      supports conclusions in the literature that Mikulicz disease, benign
      lymphoepithelial lesion, and Sjogren's syndrome may all be a part of the same
      disease process as graduated variants of one another, with malignant lymphoma
      being a recognized complication of these entities.

PMID- 14716061
TI  - Isolated abdominal wound metastasis from a gastrointestinal stromal tumor.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) frequently recur even after
      complete resection. The typical pattern of failure from GISTs is both local and
      distant with hepatic and peritoneal metastases being most common. Isolated
      abdominal-wall recurrence from GISTs has not been previously described. AIM OF
      THE STUDY: To report an isolated abdominal-wound recurrence in the absence of
      widespread disease in a patient with GIST. METHODS: Case report of a GIST and
      isolated abdominal-wound recurrence after laparoscopic-assisted en bloc
      resection. RESULTS: Elderly male patient presented with an isolated abdominal
      wall incisional recurrence 18 mo after gastric resection and adjuvant imatinib
      mesylate therapy for a high-grade GIST. CONCLUSIONS: Complete resection of
      gastrointestinal stromal tumors followed by imatinib therapy may alter the extent
      of recurrence.

PMID- 14716062
TI  - Interdisciplinary approach to abdominal Burkitt's lymphoma.
AB  - Burkitt's lymphoma is a high-grade, rapidly growing B-cell neoplasm. It is
      recognized by its aggressive course, brief median survival, and low rates of long
      term survival. The authors discuss the case of a patient who acutely presented
      with intraabdominal complications from a new onset of Burkitt's lymphoma. The
      clinical and pathological features, staging, treatment options, and survival data
      are reviewed. In addition, the role of surgical intervention is carefully
      analyzed.

PMID- 14716063
TI  - MAGE1 is expressed by a subset of pancreatic endocrine neoplasms and associated
      lymph node and liver metastases.
AB  - BACKGROUND: MAGE1 was originally isolated from human melanoma cells as a target
      antigen for autologous cytotoxic T lymphocytes. Expression of MAGE1 has
      subsequently been identified in a number of neoplastic cell types, including
      testicular germ cell and breast cancer cells, which has led to the development of
      antitumor MAGE1 vaccines. AIM OF THE STUDY: To determine if Mage-1 is expressed
      in pancreatic endocrine neoplasms (PENs) and PEN metastases. METHODS: We utilized
      immunolabeling analysis for Mage-1 on 49 primary PENs, 11 liver metastases, and 6
      lymph node metastases. A semiquantitative labeling index (LI) of 0 (no
      expression), 1, 2 (moderate expression), and 3 (intense expression, correlating
      with internal control markers) was used to determine relative amounts of MAGE1
      expression in these lesions. RESULTS: We have identified MAGE1 expression in a
      subset (42 of 49; 86%) of PENs. Normal pancreatic ducts, present in tissue
      adjacent to PENs, were utilized as a positive control for Mage-1 immunolabeling
      (index score 3); no other detectable labeling for Mage-1 was evident in normal
      pancreatic tissue. Primary PENs, with or without metastases (mean LI score 1.2 vs
      1.0, respectively), did not demonstrate a significant difference in Mage-1 LI,
      although intratumoral heterogeneity was apparent in some, but not all, of these
      lesions. Lymph node metastases (mean score 2.0) demonstrated a significant
      increase in Mage-1 LI as compared to primary, non-metastatic lesions (p =
      0.04984) and primary metastatic lesions (p = 0.02351). In contrast, six patients
      with a survival of less than one year demonstrated a low Mage-1 LI (mean score,
      0.58). CONCLUSIONS: MAGE1 expression is present in a subset of primary PENs and
      in lymph node metastases, and may therefore serve as a useful marker and
      potential therapeutic target in PENs. Furthermore, the absence of Mage-1
      expression in a subset of primary PENs may indicate a worsened prognosis.

PMID- 14716064
TI  - Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas
      containing foci of early carcinoma: correlations with cathepsin D expression and
      other malignant features.
AB  - BACKGROUND: Cathepsin D (CD) is an aspartyl lysosomal protease, and the
      prognostic value of CD expression has been studied in a variety of tumors,
      however, its role in early adenocarcinomas remains unclear. AIM OF THE STUDY: We
      evaluated the expression of CD in a series of colorectal adenomas with severe
      dysplasia containing foci of early carcinoma and compared the results to several
      histopathological and immunohistochemical features. METHODS: Adenomas were
      obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33
      adenomas contained well-differentiated adenocarcinomas and nine adenomas
      contained moderately differentiated adenocarcinomas. RESULTS: Positive CD
      expressions were observed in 25% of well-differentiated adenocarcinomas and in
      66.7% of moderately differentiated adenocarcinomas (p < 0.05). Of the 12
      adenocarcinomas with positive CD expression, four had positive CD expression in
      their adenomas (p < 0.01), 6 showed positive Ki-67 expression in their adenomas
      (NS), and 10 had positive p53 expression in their adenomas (p < 0.05). No
      significant association was seen between the level of CD expression and adenoma
      size. CONCLUSIONS: The expression of CD in adenocarcinoma correlated
      significantly with differentiation, and with the levels of CD and p53 expression
      in the adenomas of the polyp.

PMID- 14716065
TI  - The impact of liver metastasis on mortality in patients initially diagnosed with
      locally advanced or resectable pancreatic cancer.
AB  - BACKGROUND: Liver metastases are frequent in pancreatic cancer, although their
      impact on patient mortality is still unclear. METHOD: The extent of liver
      metastasis (H-III [diffuse], H-II [moderate], H-I [limited], H-0) and the
      magnitude of liver dysfunction (lf-III [failure], lf-II [severe], lf-I
      [moderate], lf-0) were reviewed in 89 locally advanced and resectable pancreatic
      cancer patients in order to determine possible relationships with mortality and
      survival. RESULTS: The extent of liver metastasis (H-III, 18; H-II, 20; H-I, 12;
      H-0, 39) and the magnitude of liver dysfunction (lf-III, 12; lf-II, 8; lf-I, 11;
      lf-0, 58) were quite variable. Based on the aforementioned two categories,
      pancreatic cancer patients could be divided into four groups: (A) extensive liver
      metastasis affecting patient mortality, 14% (12/89); (B) liver metastases that do
      not cause severe liver dysfunction, 38% (34/89); (C) severe liver dysfunction,
      not associated with liver metastasis, 9% (8/89); (D) spared liver function, with
      no liver metastasis, 39% (35/89). The median survival period of H-III patients
      (195 d) was quite short compared with those of H-I (288 d) and H-0 (240 d)
      patients. CONCLUSION: Considering patients with locally advanced and resectable
      pancreatic cancer, the fraction of cases with diffuse liver metastases is
      relatively small. Moreover, only a minor proportion of pancreatic cancer patients
      die from hepatic failure as a direct result of liver metastasis.

PMID- 14716066
TI  - Epstein-Barr virus association is rare in esophageal squamous cell carcinoma.
AB  - BACKGROUND: A critical role of Epstein-Barr virus (EBV) in carcinogenesis of
      nasopharyngeal squamous cell carcinoma and gastric adenocarcinoma is strongly
      suspected. We analyzed the possible EBV association for Japanese squamous cell
      carcinoma (SCC)-dominant esophageal cancer cases. METHODS: We retrospectively
      screened 36 surgically resected esophageal cancer lesions from 36 patients mainly
      with SCC using in situ hybridization (ISH) for EBV-encoded small RNA1 (EBER-1).
      EBV DNA analysis using real-time quantitative polymerase chain reaction (Q-PCR)
      was performed for three recent cases. RESULTS: We found no EBER-1-positive cancer
      cell in any tested esophageal cancer lesion. There were many EBER-1-positive
      tumor-infiltrating lymphocytes in the basaloid SCC lesion and a small number of
      positive lymphocytes in the other five advanced SCC lesions (14.7% of SCC). One
      SCC lesion with a highcopy number of EBV DNA had EBER-1-positive lymphocytes.
      CONCLUSIONS: EBV is rarely associated with esophageal SCC, and may appear through
      tumorinfiltrating lymphocytes in some advanced lesions.

PMID- 14716067
TI  - The surgical treatment of obstructive sleep apnea.
AB  - Obstructive sleep apnea is a highly prevalent disorder that significantly
      increases mortality when it is moderate to severe. Continuous positive airway
      pressure (CPAP) provides excellent relief to sleep apnea in the majority of
      patients. Unfortunately, many patients cannot tolerate CPAP and seek surgical
      alternatives. The reported surgical success rates range between 25 and 100% with
      most studies achieving a 50-70% success rate. The severity of the sleep apnea, as
      well as the patient's physical features influence the surgical success rate.
      Patients with mild sleep apnea should be treated if systematic. Treatment should
      be encouraged for patients with moderate to severe sleep apnea because of the
      decrease in life expectancy and other associated morbidities. Current surgical
      procedures include uvulopalatopharyngoplasty, genioglossus advancement,
      radiofrequency ablation to the base of tongue, tongue suspension,
      maxillomandibular advancement, and tracheostomy.

PMID- 14716068
TI  - Severe obstructive airway disorders and diseases: vocal fold dysfunction.
AB  - Vocal Fold Dysfunction is a syndrome characterized by abnormal adduction of the
      focal folds during inspiration and is the cause of a wide spectrum of clinical
      manifestations ranging from mild inspiratory stridor to an inability to move any
      air. Patients present with varying degrees of intermittent respiratory
      difficulty, the most severe caused by intense laryngospasm. Distinguishing Vocal
      Fold Dysfunction from Refractory Asthma is important to avoid unnecessary
      pharmacotherapy and intubation. The diagnosis of Vocal Fold Dysfunction can only
      be made with certainty by flexible fiberoptic laryngoscopy while the patient is
      symptomatic. Pulmonary function studies and a lack of response to bronchodilators
      may provide clues to the diagnosis. Most patients with the condition can be
      managed by speech therapy and the use of breathing strategies that eliminate the
      abnormal vocal fold movement. Chronic laryngeal irritation may be a trigger for
      Vocal Fold Dysfunction and conditions such as laryngopharyngeal reflux disease
      should be aggressively managed in this patient population.

PMID- 14716069
TI  - Severe bronchiectasis.
AB  - Bronchiectasis is primarily the result of airway injury and remodeling
      attributable to recurrent or chronic inflammation and infection. The underlying
      etiologies include autoimmune diseases, severe infections, genetic abnormalities,
      and acquired disorders. Recurrent airway inflammation and infection may also be
      the result of allergic or immunodeficiency states such as allergic
      bronchopulmonary mycoses or HIV/AIDS. Bronchiectasis should be included in the
      differentiation diagnosis of any patient with chronic respiratory complaints such
      as cough and sputum production. Early clinical manifestations may be subtle.
      Hallmarks of severe bronchiectasis include fetid breath, chronic cough, and
      sputum production. The associated chronic respiratory infections and airway
      sepsis are punctuated by episodes of acute exacerbation. Prompt recognition and
      treatment of bronchiectasis may allow for prevention of disease progression and
      irreversible loss of lung function. This review of severe non-cystic fibrosis
      bronchiectasis describes the current pathophysiology, clinical presentations, and
      management of bronchiectasis. We review how impaired airway clearance and the
      inability to resolve infection and inflammation creates a vicious cycle of
      recurrent injury. The common clinical features of bronchiectasis and findings are
      presented and illustrated by radiographic images. The common species and
      significance of various organisms often recovered from the distal airways
      including: tuberculous and environmental mycobacteria, aspergillus, and bacteria
      such as Pseudomonas aeruginosa will be covered. Management strategies including
      sputum surveillance, sputum clearance, antimicrobial therapy including antifungal
      and antimyobacterial agents as well as the evidence for the use of inhalational
      and anti-inflammatory therapies such as corticosteroids are also discussed.
      Recommendations for the work-up and therapy of complications including hemoptysis
      and respiratory failure are presented.

PMID- 14716070
TI  - Severe bronchiolitis in children.
AB  - Bronchiolitis is a common, acute, contagious lower respiratory tract illness of
      infants and young children. The majority of cases are secondary to respiratory
      syncytial virus. There are a number of risk factors for severe disease, including
      children less than six weeks of age and patients with atopy and/or asthma. The
      management requires vigilant monitoring and high-quality supportive care,
      including impressive use of fluids and nutritional support. Further research on
      anti-virals is essential to prevent respiratory syncytial virus induced
      bronchiolitis. Fortunately, the prognosis for the majority of normal infants who
      develop bronchiolitis is good.

PMID- 14716071
TI  - Bronchiolitis obliterans.
AB  - Bronchiolitis obliterans (BO) is a disease of small airways that results in
      progressive dyspnea and airflow limitation. It is a common sequela of bone
      marrow, lung, and heart-lung transplantation, but can also occur as a
      complication of certain pulmonary infections, adverse drug reaction, toxic
      inhalation, and autoimmune disorders. Non-transplant-related BO is rare and can
      mimic asthma and chronic obstructive pulmonary disease (COPD). In transplant
      related BO, the diagnosis can be suggested by obstructive changes in serial
      pulmonary function testings, while open lung biopsy is usually required in non
      transplant cases. High-resolution computerized tomography (HRCT) is also a
      helpful tool to diagnose and assess the severity of BO. The treatment of BO,
      regarding of the cause, is usually disappointing. Systemic corticosteroid
      immunosuppression and retransplantation have been described with variable
      success.

PMID- 14716072
TI  - Cystic fibrosis in adults: current and future management strategies.
AB  - Over 30,000 individuals in the United States of America are living with cystic
      fibrosis (CF). Despite incremental advances in care and understanding of its
      pathophysiology, CF remains a significantly life-limiting disease. Readily
      accessible newborn screening, genetic testing, and an improved awareness have
      increased the early recognition of CF, atypical presentations of CF, and the CF
      related diseases. Improvements in medical management have led to continually
      improving life expectancy for patients with CF. Despite improved management
      strategies, severe lung disease remains the commonly life-limiting pathology. We
      review the pathophysiology, diagnosis, and management of the respiratory-tract
      manifestations of CF that represent the life-limiting aspects of the condition
      and summarize upcoming and possible future therapies for patients with CF.

PMID- 14716074
TI  - Association of alpha-subunits with nucleotide-modified beta-subunits induces
      asymmetry in the catalytic sites of the F1-ATPase alpha3beta3-hexamer.
AB  - The photoaffinity spin-labeled ATP analog, 2-N3-SL-adenosine triphosphate (ATP),
      was used to covalently modify isolated beta-subunits from F1-ATPase of the
      thermophilic bacterium PS3. Approximately 1.2 mol of the nucleotide analog bound
      to the isolated subunit in the dark. Irradiation leads to covalent incorporation
      of the nucleotide into the binding site. ESR spectra of the complex show a signal
      that is typical for protein-immobilized radicals. Addition of isolated alpha
      subunits to the modified beta-subunits results in ESR spectra with two new
      signals indicative of two distinctly different environments of the spin-label,
      e.g., two distinctly different conformations of the catalytic sites. The relative
      ratio of the signals is approx 2:1 in favor of the more closed conformation. The
      data show for the first time that when nucleotides are bound to isolated beta
      subunits, binding of alpha-subunits induces asymmetry in the catalytic sites even
      in the absence of the gamma-subunit.

PMID- 14716073
TI  - Clinical and immunologic components of sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown etiology that
      affects the lungs and the lymphatic system. It is seen by specialists in allergy,
      rheumatology, and pulmonary disease. Although there are no clues to etiology, an
      environmental basis has been implicated primarily on the basis of epidemiologic
      and anecdotal data. The majority of patients are very readily diagnosed and
      should not be confused with other pulmonary disorders. Sarcoidosis can become an
      issue if it occurs in the presence of other significant pulmonary disease, such
      as patients with asthma or hypersensitivity pneumonitis. Most patients remain
      asymptomatic and many are diagnosed when picked up on a routine screening exam.
      Steroids can be used to manage some patients but caution should be exercised to
      choose the appropriate dose and to treat patients for a limited period of time to
      avoid the complications of steroids. A minority of patients do progress to
      significant disease, including morbidity and mortality, and further research is
      needed to determine more appropriate and specific therapy for such situations.

PMID- 14716075
TI  - Functionally-distinct proton-binding in HERG suggests the presence of two binding
      sites.
AB  - HERG (Human ether-a-go-go-related gene) potassium channels are crucial for
      cardiac action potential repolarization. HERG channels are also found in neuronal
      and tumor cells. The effect of pHo on HERG is of clinical significance because of
      changes in pH during myocardial ischemia, inflammation, and respiratory
      alkalosis. We present evidence for the presence of multiple proton binding sites
      in HERG. Extracellular protons bind rapidly and reversibly to affect both
      activation and deactivation. However, these effects occur in two distinct pHo
      ranges. The deactivation rate has a pKa of 6.76 +/- 0.02 compared to pKa of 5.50
      +/- 0.02 for changes in current suppression, which suggests the presence of at
      least two proton binding sites on HERG with functionally distinct properties.

PMID- 14716076
TI  - Adapting the Quesant Nomad atomic force microscope for biology and patch-clamp
      atomic force microscopy.
AB  - The Quesant Nomad atomic force microscope (AFM) was modified to produce a
      reliable patch-clamp AFM for demanding biologic applications. The AFM's laser
      optics forms the basis of a condenser that allows simultaneous Kohler
      illumination and AFM imaging on an inverted optical microscope. The original AFM
      scan head was replaced with plastic and glass to make it biologically inert. A
      bevel cut in the new scan head permits clearance for patch clamp pipets.
      Cantilevers are attached to the scan head with a quick setting silicone rubber
      that is readily removable. Software was developed to (a) automate a gentle
      approach and set a specific feedback force, (b) provide a mouse-driven control of
      the X-Y position of the probe tip and recall of saved locations, and (c) measure
      force-distance curves over user defined paths. Additional modifications were made
      to minimize mechanical noise. The patch-clamp AFM achieves 600 fA (3 kHz
      bandwidth) and 1 A RMS noise levels (10 kHz bandwidth). The correlation of
      electrical and mechanical information allows signal averaging and measures sub
      Angstrom, sub-millisecond electromotile responses from cells.

PMID- 14716077
TI  - Volume kinetic analysis of fluid shifts accompanying intravenous infusions of
      glucose solution.
AB  - Volume kinetics is a mathematical tool for macroscopic (whole-body) evaluation of
      the distribution and elimination of fluid given by intravenous infusion. Although
      the kinetic system has mostly been applied to crystalloid fluids, such as
      Ringer's solution, it has more recently been extended to glucose solution, which
      is characterized by interdependence between glucose and fluid kinetics. The
      elimination of glucose, as estimated by a one-compartment open model, serves as
      the driving force for cellular uptake of glucose and, by virtue of osmosis, of
      water. Key findings include the observation that the infused fluid, besides being
      accumulated in the cells, occupies a central body fluid space (V1), which is no
      larger than 3-4 L, and that the cellular hydration has a much longer time-course
      than the hydration of V1. This explains the risk of hypovolemia associated with
      rapid infusion of 5% glucose; the dilution of V1, which is quite substantial
      owing to the small size of this space at baseline, stimulates a brisk diuresis
      while the excess water is being "trapped" in the cells along with the glucose.
      Model linearity has been demonstrated for 2.5% glucose solution and this allows
      the construction of nomograms for administration of such fluid during surgery and
      critical illness.

PMID- 14716078
TI  - Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding.
AB  - In eukaryotic cells, the endoplasmic reticulum (ER) plays an essential role in
      the synthesis and maturation of a variety of important secretory and membrane
      proteins. For glycoproteins, the ER possesses a dedicated maturation system,
      which assists folding and ensures the quality of final products before ER
      release. Essential components of this system include the lectin chaperones
      calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a
      glycoprotein specific thiol-disulfide oxidoreductase. The significance of this
      system is underscored by the fact that CNX and CRT interact with practically all
      glycoproteins investigated to date, and by the debilitating phenotypes revealed
      in knockout mice deficient in either gene. Compared to other important chaperone
      systems, such as the Hsp70s, Hsp90s and GroEL/GroES, the principles whereby this
      system works at the molecular level are relatively poorly understood. However,
      recent structural and biochemical data have provided important new insights into
      this chaperone system and present a solid basis for further mechanistic studies.

PMID- 14716079
TI  - Tipping the apoptotic balance in Alzheimer's disease: the abortosis concept.
AB  - The mechanisms underlying the selective neuronal death in Alzheimer's disease are
      largely unresolved. Nonetheless, it is apparent that the environment of the
      diseased brain is extremely rich in pro-apoptotic stimuli and that these lead to
      an activation of the apoptotic death cascade. However, there is surprisingly
      little evidence for the completion of the death pathway indicating that the
      apoptotic death program is terminated by a mechanism termed abortosis. This
      review discusses the concept of abortosis in relation to Alzheimer's disease.

PMID- 14716080
TI  - Toward mechanical manipulations of cell membranes and membrane proteins using an
      atomic force microscope: an invited review.
AB  - Recent advances in the use of the atomic force microscope (AFM) for manipulating
      cell membranes and membrane proteins are reviewed. Early pioneering work on
      measurements of the magnitude of the force required to create indentations with
      defined depth on their surfaces and to separate interacting pairs of avidin
      biotin, antigen-antibody, and complementary DNA pairs formed the basis of this
      field. The method has subsequently been applied to map the presence of cell
      surface receptors and polysaccharides on live cell membranes by force
      measurement, with promising results. Attempts to extract phospholipids and
      proteins from lipid bilayers and live cell surfaces have been reported, providing
      a new tool for the manipulation of cellular activities and biochemical analysis
      at the single-cell level. An increasing awareness of the effect of the pulling
      speed (nm/s or microm/s), or more accurately, the force loading rate (pN/s or
      nN/s) on the magnitude of the rupture force, has led researchers to construct
      energy diagrams of rupture events based on the parameters available from such
      studies. Information on such nature of the interplay of force and loading rate is
      vital for nanomanipulation of living cells and cell membranes. Some relevant work
      for membrane manipulation using other methods is also reviewed in relation to AFM
      based methodology.

PMID- 14716081
TI  - The voltage-dependent anion channel: characterization, modulation, and role in
      mitochondrial function in cell life and death.
AB  - Recently, it has been recognized that there is a metabolic coupling between the
      cytosol and mitochondria, where the outer mitochondrial membrane (OMM), the
      boundary between these compartments, has important functions. In this crosstalk,
      mitochondrial Ca2+ homeostasis and ATP production and supply play a major role.
      The primary transporter of ions and metabolites across the OMM is the voltage
      dependent anion channel (VDAC). The interaction of VDAC with Ca2+, ATP glutamate,
      NADH, and different proteins was demonstrated, and these interactions may
      regulate OMM permeability. This review includes information on VDAC purification
      methods, characterization of its channel activity (selectivity, voltage
      dependence, conductance), and the regulation of VDAC channel by ligands, such as
      Ca2+, glutamate and ATP and touches on many aspects of the physiological
      relevance of VDAC to Ca2+ homeostasis and mitochondria-mediated apoptosis.

PMID- 14716082
TI  - Boron content in daily meals for preschool children and school youth.
AB  - Boron content in daily meals for preschool children and school youth was studied
      in this research. The boron content was measured in the meals taken from Wroclaw
      preschool and boarding school in December, March, June, and September. The whole
      meal was homogenized. Four grams of sample were mineralized and analyzed by
      inductively coupled plasma-optical emission spectroscopy (ICP-OES). Statistical
      assessment of the results was made with the Statistica v.5.1 program. The
      recovery was determined by the use of the standard additions method to evaluate
      the accuracy of the procedure. The mean boron content in 1 kg dry weight of a
      preschool meal was 2.31 mg B/kg dry wt, and in boarding-school meals, it was 2.15
      mg B/kg dry wt. Based on these results, the estimated daily boron intake was
      calculated. The daily boron intake from food by preschool children was found to
      be 1.01 mg B/d for children and 1.2 mg B/d for youth. The actual intake of boron
      from food was determined after having related the quantity of the element to 1 kg
      of body weight. In the case of children, the mean intake of boron was 0.05 mg
      B/kg body wt/d, whereas in teenagers, it was 0.016 mg B/kg body wt/d. The results
      of this research show no significant differences between daily boron intake for
      preschool children and boarding-school youth.

PMID- 14716083
TI  - Allowable level of lifetime cadmium intake calculated from the individuals in the
      Jinzu River basin of Japan.
AB  - We investigated a dose-response relationship between renal dysfunction and
      lifetime cadmium intake in individual subjects using logistic regression analysis
      and calculated the allowable level of lifetime cadmium intake among the
      inhabitants of the Jinzu River basin. From the participants of 1967 and 1968
      health examinations, target subjects in whose hamlet the cadmium concentration in
      rice was known and whose history of residence was also known were selected.
      Cadmium concentrations in rice from data analyzed by the Toyama Prefecture from
      1971 to 1976 were used. The urinary examination was done by semiquantitative
      determination of protein and glucose. All odds ratios for lifetime cadmium intake
      obtained from logistic regression analysis were more than 1 in both males and
      females who had resided in their current hamlet since birth with and without
      subjects who moved from nonpolluted areas and with or without the control group.
      The allowable levels of lifetime cadmium intake were calculated by substituting
      the abnormality rates of urinary findings of the controls 40, 50, 60, and 70 yr
      old into the logistic regression formula. The allowable levels of lifetime
      cadmium intake were less than 1.58 g for both sexes and each age group using
      proteinuria with glucosuria measurements.

PMID- 14716084
TI  - Heavy metal concentrations in the breast milk of Saudi women.
AB  - Lead, cadmium, and mercury concentrations were determined in breast milk of Saudi
      lactating mothers from Riyadh and Al-Ehssa regions in Saudi Arabia who were not
      occupationally exposed. The mean levels for cadmium, lead, and mercury were 1.732
      microg/L, 31.671 microg/L, and 3.100 microg/L, respectively. In contrast to
      mercury, mothers living in the Al-Ehssa region had significantly higher cadmium
      and lead concentrations in their breast milk than those in the Riyadh region. The
      estimated weekly intakes of cadmium, lead, and mercury of breast-fed infants in
      this study were in some cases higher than the Provisional Tolerance Weekly Intake
      (PTWI) recommended by FAO/WHO, which pose a threat to their health. This
      necessitates the urgent need to undertake a comprehensive study to determine the
      sources of exposure to these heavy metals. Breast-feeding is of great beneficial
      value for the infant's development; therefore, efforts should be made to prevent
      its contamination with environmental pollutants.

PMID- 14716085
TI  - Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain
      tissue in amyotrophic lateral sclerosis and Parkinsonism-dementia complex of Guam
      determined by High-resolution ICP-MS.
AB  - Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) are
      neurodegenerative disorders that occurred with extremely high frequency among the
      native population on Guam, especially in the 1950s and 1960s, but have
      substantially declined over the last half-century. The etiology of these diseases
      is unknown, but the most plausible hypothesis centers on imbalances in essential
      and toxic metals. We have determined the concentrations of Cd, Co, Cu, Fe, Mn,
      Rb, V, and Zn in formalin-fixed brain tissue collected during the period 1979
      1983 from eight Guamanian patients with ALS, four with PDC, and five control
      subjects using high-resolution inductively coupled plasma-mass spectrometry. The
      concentrations of Cd are markedly and significantly elevated both in gray and
      white matter in ALS, but not in PDC patients. The concentrations of Zn are
      elevated for both patient groups, in both gray and white matter, but only the
      difference in gray matter for PDC is significant. For the other metals, no
      significant differences are found.

PMID- 14716086
TI  - Levels of zinc and lipid peroxidation in acute coronary syndrome.
AB  - The present study was carried out on 20 female patients diagnosed with acute
      coronary syndrome (ACS). The control group was composed of 20 healthy female
      volunteers. Plasma malondialdehyde (MDA) levels and serum zinc (Zn), total
      cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein
      (HDL) cholesterol, and VLDL-cholesterol, Lp(a), Apo-A1, and Apo-B were determined
      in all patients and controls. Plasma MDA levels were determined to be
      significantly high in patients with ACS compared to the controls (1.75+/-0.27 vs
      0.8+/-0.43 nmol/mL; p<0.05). On the other hand, Zn levels in patients with ACS
      were determined to be significantly low compared to the control group (67.9+/
      14.8 vs 101.8+/-22.4 mg/dL; p<0.05). There was a statistically significant
      negative correlation between MDA and Zn levels in patients with ACS (r = -0.678,
      p<0.05). Other lipid parameters were significantly altered in patients with ACS
      compared to the controls (p<0.05). In conclusion, Zn and lipid peroxidation
      levels are important in patients with ACS and they must be monitored during
      diagnosis and treatment of these patients.

PMID- 14716087
TI  - Accumulation of elements in the arteries and cardiac valves of Thai with aging.
AB  - To elucidate whether the extent of element accumulation in the arteries and
      cardiac valves with aging was different between different races, the authors
      investigated the accumulation of elements in the arteries and cardiac valves of
      the Thai with aging and the relationships among elements in the cardiac valves.
      After ordinary dissection at Chiang Mai University was finished, 16 arteries and
      4 cardiac valves were resected and element contents were determined by
      inductively coupled plasma-atomic emission spectrometry. In the 16 arteries, the
      average content of calcium was the highest in the site of the abdominal aorta
      ramifying into the common iliac arteries, and it decreased in the order internal
      iliac, coronary, abdominal aorta, common iliac, external iliac, superior
      mesenteric, inferior mesenteric, thoracic aorta, brachial, radial, common
      carotid, subclavian, ulnar, axillary, renal, and internal thoracic arteries. The
      average contents of phosphorus and magnesium in respective arteries were parallel
      with the average contents of calcium, except for the coronary artery. In
      comparison with the arteries of the Japanese, the trend of calcium accumulation
      in the arteries of the Thai was almost similar to that in the arteries of the
      Japanese, except for the coronary artery and thoracic aorta. The calcium
      accumulation in the coronary artery was much higher in the Thai than in the
      Japanese, whereas that in the thoracic aorta was lower in the Thai than in the
      Japanese. Regarding elements in the cardiac valves, the calcium content increased
      remarkably in the seventies in the aortic valve and in the nineties in the
      pulmonary valve, but it hardly increased in both the mitral and tricuspid valves
      with aging. The average content of calcium was the highest in the aortic valve,
      and it decreased in the order pulmonary, tricuspid, and mitral valves. Regarding
      the relationship among elements in the aortic valves, it was found that there
      were extremely significant direct correlations among the contents of calcium,
      phosphorus, and magnesium, whereas there were significant direct correlations
      between zinc and either calcium or phosphorus contents. Although significant
      correlations were found between sulfur and the other element contents in the
      aortic valves fo the Japanese, no significant correlations were found between
      them in the aortic valves of the Thai. In the mitral valves, extremely or very
      significant direct correlations were found among the contents of calcium,
      phosphorus, magnesium, and sulfur, with some exceptions that there were no
      significant correlations between phosphorus and either magnesium or sulfur
      contents. in addition, no significant correlation was found in the calcium
      content between the aortic valve and coronary artery in the same individuals.

PMID- 14716088
TI  - Age-related changes of elements in human thoracic ducts and azygos veins and
      relationships among elements.
AB  - To elucidate compositional changes of the thoracic duct with aging, the authors
      investigated age-related changes of elements in the thoracic ducts in comparison
      with the azygos veins. The subjects consisted of 22 men and 1 woman, ranging in
      age from 65 to 95 yr. After ordinary dissection, the thoracic ducts and azygos
      veins were resected from the subjects and element contents were determined by
      inductively coupled plasma-atomic emission spectrometry. It was found that
      calcium appeared to increase in the thoracic duct with aging, but the other
      elements, such as phosphorus, sulfur, magnesium, iron, zinc, and sodium, did not
      change significantly with aging. In the azygos vein, both calcium and sulfur
      increased significantly with aging. Regarding the relationship among elements,
      extremely significant direct correlations were found among calcium, phosphorus,
      sulfur, and magnesium in the thoracic ducts, except for phosphorus and magnesium
      contents with a very significant direct correlation. In the azygos veins,
      significant direct correlations were found between calcium and sulfur contents
      and between sulfur and magnesium contents. However, no significant correlations
      were found among calcium, phosphorus, and magnesium in the azygos veins. These
      results revealed that with regard to the relationship among calcium, phosphorus,
      and magnesium, the thoracic duct was similar to the arteries, but not to the
      azygos vein.

PMID- 14716089
TI  - Activity of neutrophil NADPH oxidase in iron-deficient anemia.
AB  - This study was designed to measure the effects of iron supplementation on
      respiratory burst in iron-deficient anemia. The performance of neutrophils was
      evaluated by measuring the activity of NADPH oxidase in 18 patients with iron
      deficient anemia before and after body iron stores are saturated. The activity of
      NADPH oxidase was significantly lower in pretreatment patients relative to
      controls (p<0.05). The activity increased after iron supplementation to levels
      that had no significant differences relative to controls.

PMID- 14716090
TI  - Effect of iron supplementation on oxidative stress and antioxidant status in iron
      deficiency anemia.
AB  - This study was designed to measure the effect of iron supplementation on
      antioxidant status in iron-deficient anemia, including the time for hemoglobin
      normalization and at the time of filling of iron body stores. The extent of
      plasma lipid peroxidation was evaluated by measuring the levels of
      malondialdehyde and glutathione peroxidase (GSH-Px), and the activities of
      superoxide dismutase (SOD) and catalase in 63 patients with iron-deficiency
      anemia before and after 6 wk of iron supplementation and at the time when body
      iron stores are saturated. After 6 wk of iron supplementation, a significant
      decrease of oxidative stress was observed in the treated subjects relative to
      controls (p<0.05). No significant differences existed between treated patients at
      6 wk and at the end of the study. The erythrocyte levels of catalase, SOD, and
      GSH-Px were significantly lower in treated patients relative to controls
      (p<0.05). These levels increased after 6 wk of supplementation (p<0.05) and
      showed no significant differences with those at the end of the study.

PMID- 14716091
TI  - Computer simulation of Zn(II) speciation and effect of Gd(III) on Zn(II)
      speciation in human blood plasma.
AB  - The speciation and distribution of Zn(II) and the effect of Gd(III) on Zn(II)
      speciation in human blood plasma were studied by computer simulation. The results
      show that, in normal blood plasma, the most predominant species of Zn(II) are
      [Zn(HSA)] (58.2%), [Zn(IgG)](20.1%), [Zn(Tf)] (10.4%), ternary complexes of
      [Zn(Cit)(Cys)] (6.6%) and of [Zn(Cys)(His)H] (1.6%), and the binary complex of
      [Zn(Cys)2H] (1.2%). When zinc is deficient, the distribution of Zn(II) species is
      similar to that in normal blood plasma. Then, the distribution changes with
      increasing zinc(II) total concentration. Overloading Zn(II) is initially mainly
      bound to human serum albumin (HSA). As the available amount of HSA is exceeded,
      phosphate metal and carbonate metal species are established. Gd(III) entering
      human blood plasma predominantly competes for phosphate and carbonate to form
      precipitate species. However, Zn(II) complexes with phosphate and carbonate are
      negligible in normal blood plasma, so Gd(III) only have a little effect on
      zinc(II) species in human blood plasma at a concentration above 1.0 x 10(-4) M.

PMID- 14716092
TI  - Effects of the Ca ionophore a23187 on zinc-induced apoptosis in C6 glioma cells.
AB  - Zinc ions are essential, but at elevated concentrations, they also have toxic
      effects on mammalian cells. Zinc plays a crucial role in cell proliferation and
      differentiation and it even protects cells against apoptosis caused by various
      reagents. On the other hand, zinc at high concentrations causes cell death that
      was characterized as apoptotic by internucleosomal DNA fragmentation, formation
      of apoptotic bodies, and breakdown of the mitochondrial membrane potential. In
      the present work, a clone of rat C6 glioma cells that was resistant to toxic
      effects of ZnCl2 up to 250 microM was employed to study the effect of the
      ionophore A23187 on zinc-induced apoptosis. Neither 150 microM Zn2+ nor 100 nM
      A23187 alone caused apoptosis as measured by internucleosomal DNA fragmentation.
      However, combined exposure of C6 cells to 100 nM A23187 and 150 microM Zn2+ for
      48 h was effective in inducing apoptosis. Because the so-called calcium ionophore
      A23187 is not specific for Ca2+ ions but also transports Zn2+ with high
      selectivity over Ca2+, we investigated whether this substance promoted the uptake
      of Zn2+ ions into C6 cells. Employing the zinc-specific fluorescence probe
      Zinquin, we observed that the very low concentration of 1.9 nM A23187
      significantly and rapidly raised the intracellular mobile Zn2+ content. Analysis
      by atomic absorption spectroscopy revealed that incubation with 1.9 nM A23187
      caused a doubling of the total intracellular zinc level within 60 min. We
      conclude that the apoptosis evoked by the combined action of Zn2+ and A23187 was
      the result of enhanced Zn2+ influx evoked by the ionophore, resulting in higher
      intracellular zinc levels.

PMID- 14716093
TI  - Pharmacological levels of copper exert toxic effects in Caco-2 cells.
AB  - Copper might be toxic to human intestinal cells because of its ability to
      catalyze the formation of free radicals. The aim of the present study was to
      quantify toxicological effects of increasing copper concentrations in
      preconfluent, colonic cancerous cells as well as in postconfluent,
      differentiating Caco-2 cells. Our results indicate that postconfluent cells might
      be more sensitive to copper toxicity. A significant rise of lactate dehydrogenase
      (LDH) release (150 microM or above) and decrease of cell proliferation (100
      microM or above) with increasing copper levels was found, as compared to the
      control. To the contrary, preconfluent cells were not significantly affected by
      copper (LDH release) or, if so, only at a concentration of 250 microM
      (proliferation). Loss of viability and morphological changes, including loss of
      adherence and cell rounding, were visible after incubation with 250 microM copper
      in both groups. Superoxide dismutase (SOD) activities were not affected by
      copper. Glutathione peroxidase (GSH-Px) and catalase activities were higher in
      copper-treated cells, especially in the postconfluent ones (nevertheless, the
      results were not significant because of high standard deviations). In conclusion,
      we demonstrated that copper exerts intracellular, toxicological effects on both
      groups of Caco-2 cells, although the effects seem to be more evident in the
      postconfluent (enterocytelike) group. Risk assessment, especially for high
      concentrations, might be of special interest.

PMID- 14716094
TI  - Responsiveness of total content changes of magnesium and zinc status in patients
      infected with Giardia intestinalis.
AB  - The aim of the study was to investigate the changes of total content of the
      essential elements of zinc and magnesium levels in patients infected with Giardia
      intestinalis. Zinc and magnesium concentrations were measured in 64 patients who
      were positive for the intestinal parasite G. intestinalis. Scores were obtained
      for the positives and their 60 age- and sex-matched G. intestinalis- negative
      healthy controls. The mean concentration of magnesium in blood was significantly
      lower in G. intestinalis-positive patients than in their controls both in females
      (p<0.05) and males (p<0.05). The average zinc concentration in G. intestinalis
      positive female patients was 0.76+/-0.3 mg/L and it was 0.60+/-0.2 mg/L in
      controls (p>0.05). The mean values of the zinc in blood were 0.73+/-0.2 mg/L in
      G. intestinalis-positive male patients and 0.82+/-0.1 mg/L in controls (p>0.05).
      No correlation could be demonstrated between age and mean values of zinc and
      magnesium in both G. intestinalis-positive females/males and controls (p>0.05).
      No significant correlation could be found between blood zinc and magnesium levels
      in G. intestinalis-positive female/male patients and controls (p>0.05). Magnesium
      levels were found to be clearly decreased, whereas no change was observed in zinc
      level in the patients infected with G. intestinalis compared to controls.

PMID- 14716095
TI  - Concentration of selected elements in the roots and crowns of both primary and
      permanent teeth with caries disease.
AB  - We examined the differences between the concentrations of chemical elements in
      caries-changed primary teeth and permanent ones with a division into the root and
      the crown. The study comprised 27 children aged from 4 to 11 yr and 36 adults
      aged from 36 to 71 yr. We examined the elements with the total reflection X-ray
      fluorescence method. The lowest concentrations of calcium, manganese, strontium,
      lead, and copper were in the roots of primary teeth compared to the roots of
      permanent ones. The calcium, nickel, zinc, lead, and copper concentrations were
      significantly higher in the roots of primary teeth than in the roots of permanent
      teeth. However, the zinc concentration was higher both in the root and crown of
      primary teeth than in permanent teeth. On the basis of our investigations, we can
      conclude that the content of some elements (manganese, copper, strontium, and
      lead) is higher in caries permanent teeth than in primary ones. The nickel and
      zinc concentrations are higher in the teeth of the children than the adults.
      However, the content of other elements (calcium, chromium, iron) is similar in
      both kinds of teeth.

PMID- 14716096
TI  - Melatonin supplementation can ameliorate the detrimental effects of heat stress
      on performance and carcass traits of Japanese quail.
AB  - Melatonin, the major pineal hormone, modulates growth in poultry by influencing
      hormones involved in growth. We investigated the effects of dietary melatonin
      supplementation on performance, carcass characteristics, and excretion of
      nitrogen and some minerals in broiler Japanese quails (Coturnix coturnix
      japonica) exposed to high-ambient-temperature stress (34 degrees C). One hundred
      twenty Japanese quails (10 d old) were randomly assigned to 4 treatment groups, 3
      replicates of 10 birds each. The birds were kept in either an environment
      controlled room at a constant 22 degrees C or were kept at 22 degrees C for 16
      h/d and at 34 degrees C for 8 h/d (9:00 AM to 5:00 PM). At both temperatures
      birds were fed either a basal diet or the basal diet supplemented with 40 mg of
      melatonin per kilogram of diet. The experiment lasted for 32 d. Melatonin
      improved feed efficiency in both temperatures groups compared with their
      corresponding controls. Although feed intake was similar in all groups, the
      improvement in feed efficiency was more noticeable in melatonin-fed quails kept
      at high temperature (p< 0.01). Supplemental melatonin significantly increased
      live weight gain and carcass characteristics under stress conditions (p < 0.01)
      but did not show the same effect at thermoneutral conditions (p > 0.05). Heat
      exposure increased excretion of N, Ca, P, Zn, Fe, and Cr and decreased retention
      rates for them. Dietary melatonin supplementation returned these values to normal
      (p < 0.01). No interactions between melatonin and temperature were found in the
      parameters measured. The results of the study show that melatonin supplementation
      attenuated the retardation in performance as well as the excretion of minerals
      caused by heat stress in broiler quails. Our data suggest that melatonin might
      offer protection against heat-stress-related depression in the performance of
      broiler quails.

PMID- 14716097
TI  - Vitamin E and selenium supplementation to alleviate cold-stress-associated
      deterioration in egg quality and egg yolk mineral concentrations of Japanese
      quails.
AB  - The effects of vitamin E (dl-alpha-tocopheryl acetate) and selenium (Se; Na2
      SeO3) on egg production, egg quality, and mineral content of egg yolk in Japanese
      quails reared under a low ambient temperature (6 degrees C) were evaluated. Birds
      (n=300; 7 wk old) were randomly assigned to 12 treatment groups, 25 birds per
      group. The birds in a 3 x 2 factorial design received either three levels of
      vitamin E (125, 250, and 500 mg/kg diet) or two levels of selenium (0.1 or 0.2
      mg/kg diet). After 2 wk on feed, six groups of the birds were maintained at 18
      degrees C (thermoneutral temperature [TN]), and the other half were acclimated
      over 3 d to a decreased environmental temperature of 6 degrees C (cold stress
      [CS]). The performance, egg quality, and mineral content of egg yolk were not
      influenced by supplemental vitamin E and selenium in quails not exposed to cold
      stress (p > or = 0.09). Two hundred fifty and 500 mg vitamin E/kg diet compared
      with 125 mg/kg diet and higher dietary selenium inclusions (0.2 vs 0.1 mg/kg)
      resulted in a better body weight, egg production, and feed efficiency (p = 0.01)
      in quails reared under CS. Similarly, egg weight, egg specific gravity, eggshell
      thickness, and Haugh unit were positively influenced with vitamin E (p = 0.01)
      and selenium (p < or = 0.05) supplementation. Egg yolk concentrations of Zn, Fe,
      and Mn were higher with higher dietary vitamin E (p = 0.01) and selenium (p =
      0.05). There was no interaction detected for parameters measured in the present
      study (p > or = 0.3). The results of the present study showed that a combination
      of 250 or 500 mg vitamin E and 0.2 mg selenium per kilogram of diet provides the
      greatest effects on performance and egg quality of Japanese quails reared under
      cold stress and suggest that such a supplementation can be considered as a
      protective management practice in Japanese quail diets to reduce the detrimental
      effects of cold stress.

PMID- 14716098
TI  - A model of aluminum exposure associated with lipid peroxidation in rat brain.
AB  - We have developed a rat model to investigate the relationship between aluminum
      exposure and aluminum accumulation, and with oxidative damage in brain tissues.
      Intraperitoneal injections of aluminum lactate for 7 wk (the total aluminum
      dosage per rat was approx 100 mg) significantly increased aluminum levels in the
      brain. The concentration of lipid peroxidation products (thiobarbituric acid
      reactive substances [TBARS]) also increased in the brain following aluminum
      lactate injections. No significant correlations between the concentrations of
      aluminum and of TBARS were found in the whole brain. Subcellular analysis
      revealed that aluminum lactate injections led to a significant increase in the
      concentration of aluminum in the mitochondrial fraction but had no significant
      effect on the concentration of peroxides in any subcellular fraction. These
      results suggest that aluminum accumulation induced by the aluminum lactate
      administration associates with the acceleration of lipid peroxidation in rat
      brain. Furthermore, these data indicate that the pro-oxidant effect of aluminum
      may be indirect and concentration independent. The experimental conditions used
      here provide an animal model of aluminum accumulation in the brain that should
      prove useful for further investigations of the mechanisms of aluminum
      neurotoxicity.

PMID- 14716099
TI  - Negative inotropic response to cerium in ventricular papillary muscle is mediated
      by reactive oxygen species.
AB  - This study was performed with the objective of assessing the mechanical response
      of the myocardium to different levels of cerium and delineation of the mechanism
      underlying the mediation of the functional changes. Rat ventricular papillary
      muscle was used as the experimental model. Isolated papillary muscles were
      exposed to different concentrations of CeCl3 and the force of contraction was
      measured using a force transducer. Experiments have revealed that the negative
      inotropic response to CeCl3 was proportional to its concentration. The inotropic
      changes were found to be completely reversible at concentrations < or =5 microM,
      and partially reversible at higher concentrations. Neutralization of cerium
      induced inotropic changes by the superoxide anion scavenger superoxide dismutase
      (SOD) at concentrations < or =5 microM indicates that the mechanical changes are
      mediated by reactive oxygen species. At higher concentrations of Ce3+, SOD
      partially reversed the contractile changes. The beneficial effect of SOD was seen
      only if the muscles were pretreated with the scavenger prior to the addition of
      cerium chloride.

PMID- 14716100
TI  - Copper-mediated oxidative stress in rat liver.
AB  - Copper is an essential trace element with various biological functions. Excess
      copper, however, is extremely toxic, leading to many pathological conditions that
      are consistent with oxidative damage to membranes and molecules. Exposure to high
      levels of copper results in various changes in the tissues. In liver, hypertrophy
      of hepatocytes, hepatitis, hepatocellular necrosis, and hepatocellular death are
      the results. Lipid peroxidation causes dysfunction in the cell membrane,
      decreased fluidity, inactivation of receptors and enzymes, and changes ion
      permeability. In this study, we aimed to determine the effect of copper on
      oxidative and antioxidative substances in plasma and liver tissue in a rat model.
      Sixteen male Sprague-Dawley rats were divided into two groups: Group 1 rats
      included control rats given tap water. Group 2 rats were given water containing
      copper in a dose of 100 microg/mL. All rats were sacrificed at 4 wk under ether
      anesthesia. Plasma and liver superoxide dismutase (SOD) activities, plasma and
      liver MDA (malondialdehyde) levels, and liver glutathione (GSH) levels were
      studied. Plasma and liver SOD activities were found to be higher in group 2 than
      those in group 1. Although plasma MDA levels were higher in group 2, MDA levels
      in liver tissues were comparable. Liver tissue glutathione levels were lower in
      group 2. It was concluded that although copper is needed in trace amounts, an
      excess amount is toxic for the organism. It increases lipid peroxidation and
      depletes GSH reserves, which makes the organism more vulnerable to other
      oxidative challenges.

PMID- 14716101
TI  - Localization of glycogen in the placenta and fetal and maternal livers of cadmium
      exposed diabetic pregnant rats.
AB  - This study was designed to investigate the effects of Cd exposure on the glycogen
      localization in the placenta and in fetal and maternal livers in streptozotocin
      (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200
      220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy,
      the rats were divided into four experimental groups (control, Cd treated, STZ
      treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously
      daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy
      throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single
      intraperitoneal injection of STZ in the STZ-treated group. In addition to the
      daily injection of Cd, a single intraperitoneal injection of STZ was also given
      on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last
      injection 24 h before being sacrificed and 10 randomly selected rats in each
      group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for
      determination of the serum glucose and insulin levels. Fetal and maternal livers
      of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy,
      whereas placentas were harvested only on d 20 of pregnancy for histochemical
      examination. Although both Cd and STZ caused hyperglycemia and decreased insulin
      secretion, Cd-alone treatment increased the glycogen content only in the
      placental labyrinth, whereas STZ-alone treatment increased the glycogen content
      only in the maternal part of the placenta. Increased glycogen localization was
      observed in both the placental labyrinth and the maternal part of placenta when
      Cd and STZ were given together. Fetal and maternal livers of control and other
      treatment groups were not different regarding the glycogen content on d 15 or d
      20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce
      a glycogen localization in the placenta of diabetic rats. However, the function
      and the mechanisms of increased glycogen contents in the placenta of Cd-exposed
      pregnant diabetic rats remain unclear and further studies are needed.

PMID- 14716102
TI  - Effects of zinc deficiency and supplementation on the glycogen contents of liver
      and plasma lactate and leptin levels of rats performing acute exercise.
AB  - The aim of the present study was to investigate how zinc (Zn) deficiency and
      supplementation affect glycogen content of the liver and plasma lactate and
      leptin levels of rats performing acute swimming exercise just before the blood
      samples were obtained. Four sets of 10 rats each served as the (1) Zn-deficient
      group, (2) Zn-supplemented group, (3) swimming controls, and (4) normal controls.
      Plasma lactate levels of Zn-deficient animals were significantly higher than
      those in the other three groups (p<0.01), and those in the swimming controls
      (group 3) were significantly higher than in the Zn-supplemented animals, group 2
      (p<0.01). The plasma glucose of the Zn-deficient group was significantly higher
      than all other groups (p<0.01) and that of group 2 was significantly lower than
      group 4 (p<0.01). Glycogen levels in liver of the Zn-deficient animals was
      significantly lower than groups 2 and 4 (p<0.01), and, in turn, were higher than
      for group 3 (p<0.01). The plasma leptin and Zn levels of group 1 were
      significantly lower than in all other groups (p<0.01). These results suggest that
      Zn deficiency exerts a negative influence in the above-mentioned parameters and
      that Zn supplementation has the opposite effect.

PMID- 14716103
TI  - Effect of zinc and melatonin supplementation on cellular immunity in rats with
      toxoplasmosis.
AB  - The effects of zinc (Zn) and/or melatonin supplementation on cellular immunity
      were investigated in rats infested with Toxoplasma gondii. Fifty Sprague-Dawley
      male rats were used for this study. All animals were fed a normal diet, ad
      libitum, containing 97 mg Zn/kg. They were divided into five experimental groups,
      as follows. Group I (n = 10) received intraperitoneal injections of zinc sulfate
      at a dose of 3 mg/kg/d for 3 wk. Group II (n = 10) received intraperitoneal
      injections of melatonin at a dose of 3 mg/kg/d for 3 wk. Group III (n = 10)
      received intraperitoneal injections of zinc sulfate (3 mg/kg/d) and melatonin (3
      mg/kg/d) for 3 wk. Group IV (n = 10) was infested controls. Group V (n = 10) was
      healthy controls. There were no differences in the percentage of CD3+ lymphocytes
      among all groups. For groups I-III, the CD4+ and CD8+ ratios were higher than
      those of the groups IV and V controls (p<0.01). Similarly, the total lymphocyte
      ratios in groups I-III were higher than those of infested and healthy controls
      (p<0.01). The total lymphocyte ratios in group III were significantly higher than
      those of groups I and II (p<0.01). The plasma Zn levels in the supplemented
      groups were significantly higher than those of control groups IV and V (p<0.01).
      These results suggest that melatonin and/or Zn supplementation may activate
      cellular immunity by stimulating CD4+ and CD8+ production in infected rats with
      T. gondii.

PMID- 14716104
TI  - Zinc prevention of electromagnetically induced damage to rat testicle and kidney
      tissues.
AB  - The aim of this study was to investigate the extent of lipid peroxidation when
      zinc is administered to rats periodically exposed to a 50-Hz electromagnetic
      field for 5 min at a time over a period of 6 mo. Twenty-four Sprague-Dawley adult
      male rats were subdivided in groups of eight animals each. Group 1 served as
      untreated controls, group 2 was exposed to an electromagnetic field but received
      no additional treatment, and group 3 was exposed to electromagnetic radiation and
      treated with 3-mg/kg daily intraperitoneal injections of zinc sulfate. The
      erythrocyte glutathione activity (GSH) and the plasma, testicle, and kidney
      tissue levels of zinc (Zn) and of malondialdehyde (MDA) were measured in all of
      the animals. The plasma and testicle MDA levels in group 2 were higher than those
      in groups 1 and 3, with group 3 values significantly higher than those in group 1
      (p<0.001). The kidney MDA levels in group 2 were higher than in groups 1 and 3
      (p<0.001). The erythrocyte GSH level was lower in group 2 than in groups 1 and 3,
      with group 1 significantly lower than group 3 (p<0.001). In testicle and kidney
      tissues, the GSH levels in group 1 were lower than for groups 2 and 3, with group
      2 significantly lower than group 3 (p<0.001) The plasma zinc levels were highest
      in group 3, followed by group 1 and group 2, which showed the lowest value
      (p<0.001). These results indicate that testicle and kidney tissue damage caused
      by periodic exposure to an electromagnetic field are ameliorated or prevented by
      zinc supplementation.

PMID- 14716105
TI  - Effects of zinc and melatonin deficiency on testicular tissue of rats.
AB  - The present study was designed to investigate the effects of zinc and/or
      melatonin deficiency on rat testes. A total of 24 adult male Sprague-Dawley rats
      were used in this study. The rats were divided into four groups of six rats each,
      as follows: (I) controls, (II) zinc deficient, (III) pinealectomized, zinc
      normal, and (IV) pinealectomized, zinc deficient. The plasma zinc levels in the
      control group were higher than in all the other groups (p<0.01), and those of the
      zinc-deficient groups II and IV were significantly lower than for group III
      (p<0.01). The melatonin levels in the controls were also significantly higher
      than for all other groups (p<0.01) There was no significant difference in sperm
      production between the controls and the group of animals that had no epiphysis. A
      significant suppression was observed in the spermatogenetic activity of the zinc
      deficient groups (p<0.01). The suppression was higher in group II than in group
      IV. These results indicate that testicular damage caused by zinc deficiency may
      be reduced by melatonin deficiency.

PMID- 14716106
TI  - Effects of Nigella sativa L. and Urtica dioica L. on selected mineral status and
      hematological values in CCl4-treated rats.
AB  - This study was designed to investigate the effects of Nigella sativa L. (NS),
      known as black seed, or/and Urtica dioica L. (UD), known as stinging nettle root,
      treatments on serum Na, K, Cl, and Ca levels and some hematological values of
      CCl4-treated rats. Sixty healthy male Sprague-Dawley rats, weighing 250-300 g,
      were randomly allotted into 1 of 4 experimental groups: A (CCl4-only treated), B
      (CCl4+UD treated), C (CCl4+NS treated), and D (CCl4+UD+NS treated), each
      containing 15 animals. All groups received CCl4 (0.8 mL/kg of body weight,
      subcutaneously, twice a week for 90 d starting d 1). In addition, B, C, and D
      groups also received the daily ip injection of 0.2 mL/kg NS and/or 2 mL/kg UD
      oils for 45 d starting d 46. Group A, on the other hand, received only 2 mL/kg
      normal saline solution for 45 d starting d 46. Blood samples for the biochemical
      analysis were taken by cardiac puncture from five randomly chosen rats in each
      treatment group at the beginning, d 45, and d 90 of the experiment. The CCl4
      treatment for 45 d significantly (p<0.05) increased the serum K and Ca and
      decreased (p<0.05) the red blood cell count (RBC), white blood cell count (WBC),
      packed cell volume (PCV), and Hb levels without changing (p>0.05) the serum Na
      and Cl levels. NS or UD treatments (alone or combination) for 45 d starting d 46
      significantly (p<0.05) decreased the elevated serum K and Ca levels and also
      increased (p<0.05) the reduced RBC, WBC, PCV, and Hb levels. It is concluded that
      NS and/or UD treatments might ameliorate the CCl4-induced disturbances of anemia,
      some minerals, and body's defense mechanism in CCl4-treated rats.

PMID- 14716107
TI  - Effect of overdose zinc on mouse testis and its relation with sperm count and
      motility.
AB  - The purpose of this study was to investigate the effects of excessive zinc intake
      on the testes and on sperm count and motility in mice. Thirty Balb c mice were
      divided randomly into 3 groups of 10 animals in each. Group I acted as controls;
      group II was supplied with drinking water containing 1.5 g/100 mL Zn, and group
      III was supplied with drinking water containing 2.5 g/100 mL Zn. The animals were
      sacrificed after 3 wk supplementation and the epididymis and testis were quickly
      excised. A negative correlation between Zn dose and sperm count and motility was
      found. The sperm count in group III was significantly lower than in groups II and
      I (p<0.05). The sperm motility in group III was significantly lower than in the
      controls (p<0.05). Degenerative changes, including spermatic arrest, degeneration
      of seminiferous tubules, and fibrosis in interstitial tissue, were observed in
      group III animals. These results show that high doses of zinc significantly alter
      sperm motility.

PMID- 14716108
TI  - Summated chemotherapy dose-intensity versus loco-regional response in locally
      advanced breast cancer: its possible implications.
AB  - BACKGROUND: Summated dose-intensity (SDI) of chemotherapy regimen could influence
      the outcome in malignancies. AIMS: To evaluate the implication of SDI and
      identify key drugs for loco-regional response in locally advanced breast cancer
      (LABC). SETTINGS AND DESIGN: This retrospective study was based on audit of
      records of LABC patients who had received neoadjuvant chemotherapy (NACT).
      MATERIAL AND METHODS: Actual unit dose-intensity (UDI) of each drug and
      corresponding SDI of every doxorubicin (n=116 cycles) or non-doxorubicin (n=110
      cycles) based NACT received by 42 patients of LABC were summated. Cumulative dose
      intensity (CDI) for individual drugs and cumulative SDI (CSDI) for the entire
      course of NACT were estimated and correlated with quantum of primary tumor,
      axillary and supraclavicular nodal responses. STATISTICAL ANALYSIS USED: Two
      sided chi-square, t-test, step-wise regression was used. RESULTS: Dose-response
      curve between CSDI and corresponding responses for both primary and lymph nodes
      were sigmoid in shape for both doxorubicin or non-doxorubicin based NACT. Curves
      were best fitted using a cubic fit for all patients (r2 = 0.82, 0.84 and 0.93 for
      primary tumor, axillary and supraclavicular lymph nodes respectively). CSDI
      emerged as an important prognosticators for both primary (P<0.001) and nodal
      (P<0.001) responses. Individually, CDI of 5-fluorouracil for primary (P<0.001),
      CDIs of doxorubicin (P<0.001) and methotrexate (P=0.006) for axillary nodes and
      CDI of cyclophosphamide (P=0.001) for supraclavicular nodes were significant.
      CONCLUSIONS: Loco-regional responses in LABC are dependent on CSDI of NACT
      regimen. Drugs for high-dose intensification protocols could be identified and
      chosen based on the impact of CDI of individual drugs in NACT.

PMID- 14716109
TI  - Cytogenetics and fluorescence in-situ hybridization in detection of hematological
      malignancies.
AB  - BACKGROUND: The technique of Fluorescence In-Situ Hybridization (FISH), a hybrid
      of cytogenetics and molecular biology has increased the resolution and
      application of cytogenetics in various neoplastic processes. In various types of
      leukemias, primary investigation by conventional cytogenetic [CC] technique
      followed by FISH has increased our understanding of the abnormal clonal formation
      involving different gene region. AIMS: Present study is aimed to use different
      kinds of in-house FISH probes in various hematological malignancies and its
      correlation with conventional cytogenetic finding. MATERIAL AND METHODS:
      Cytogenetic study was carried out in 360 patients either from peripheral blood or
      from bone marrow cells suspected for various types of leukemias. Four of 360
      cases were further selected for FISH study by using different types of in-house
      probes, such as BAC [Bacterial Artificial Chromosome], PAC [Phague Artificial
      Chromosome], alphoid, PCP [Partial Chromosome Paint] and WCP [Whole Chromosome
      paint]. RESULTS: The results confirmed breakpoints of inversion 16 and del 16 in
      case 2 and 3 respectively. Whereas, case 1 did not confirm the cytogenetic
      findings of t(15;17) by PML/RARa fusion signals as multiple cell lines were
      involved in the patients. PCP and WCP were helpful in the identification of the
      marker chromosome in case 1. Telomeric and centromeric probes confirmed the
      cytogenetic findings of t(5;7) in case 4. CONCLUSION: We observe from this study
      that, in addition to the conventional cytogenetic study, FISH study provide
      further confirmation of chromosomal rearrangements. This facilitates our
      understanding of the neoplastic process more precisely for the better
      prognostication of the patient.

PMID- 14716110
TI  - Early relapse after non myeloablative allogeneic stem cell transplantation in a
      patient with acute promyelocytic leukemia in complete molecular remission.
AB  - We described a 41-year-old patient with acute promyelocytic leukemia (APL) who
      experienced two successive relapses: one after all-trans retinoic acid (ATRA)
      treatment and chemotherapy, and another after ATRA treatment and chemotherapy,
      followed by autologous peripheral blood stem cell transplantation. A third
      complete remission (CR) was achieved with arsenic trioxide (As2O3) therapy. Mini
      transplantation was performed as consolidation therapy. While the patient was in
      molecular remission at the beginning of conditioning regimen, a new relapse arose
      after transplantation at time of cell recovery. This raises a potential
      relationship between relapse and the severe immunosuppression induced by mini
      transplantation. To our knowledge, this is the first description of a mini
      allograft in an APL patient achieving molecular remission after As2O3 therapy.

PMID- 14716111
TI  - Chronic myeloid leukemia presenting with absence of basophils and marked
      dyspoiesis.
AB  - A 61-year old woman presented to us with fever, weakness and ecchymotic patches
      for one year. She had leucocytosis, anemia and thrombocytopenia. Peripheral blood
      smear showed 62% neutrophils, 32% myelocytes and metamyelocytes, 2%
      promyelocytes, 1% blasts, 2% monocytes, 1% lymphocytes but no basophils and
      marked dyspoiesis. Bone marrow picture was essentially the same. A diagnosis of
      atypical chronic myeloid leukemia was suggested. The correct diagnosis of chronic
      myeloid leukemia-accelerated phase was, however, made on cytogenetic analysis
      which showed Philadelphia chromosome (Ph) and isochromosome 17q [i(17q)]. This
      case describes a rare and diagnostically difficult presentation of CML arising
      out of a combination of prominent dyspoiesis and near absence of peripheral blood
      basophils.

PMID- 14716112
TI  - Positron emission tomography imaging in evaluation of cancer patients.
AB  - Positron emission tomography (PET) is a diagnostic imaging technique that has
      progressed rapidly from being a research technique in laboratories to a routine
      clinical imaging modality. The most widely used radiotracer in PET is Fluorine18
      fluorodeoxyglucose (F18-FDG), which is an analogue of glucose. The FDG uptake in
      cells is directly proportional to glucose metabolism of cells. Since glucose
      metabolism is increased many fold in malignant tumors PET has a high sensitivity
      and a high negative predictive value. PET with FDG is now the standard of care in
      initial staging, monitoring the response to the therapy, and management of lung
      cancer, colonic cancer, lymphoma, melanoma, esophageal cancer, head and neck
      cancer and breast cancer. Other indications of PET like bone tumor, ovarian
      cancer and cancer of unknown primary (CUP) has also been discussed in brief. The
      aim of this review article is to review the clinical applications of PET in
      various malignancies and only limited number of important studies will be
      discussed for this effort.

PMID- 14716113
TI  - Role of chemoradiation in advanced cervical cancer.
AB  - A prospective randomized study was conducted in our department of Radiotherapy,
      Regional Institute of Medical Sciences, Imphal to evaluating the role of
      chemoradiation in the management of advanced inoperable cervical cancer (stage
      IIB-IIIB) taking only radiation treatment as control spanning the period 1996
      1999. Of the fifty patients accumulated in the study group, three patients did
      not complete treatment, one expired due to other causes and three were lost to
      follow up. Likewise, of the forty-six patients in the control group, one patient
      did not complete treatment and 4 were lost to follow up. Thus only 43 and 41
      patients were available for the result analysis for the study and control groups
      respectively. The early treatment response as assessed after two months of
      treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete
      response (CR), partial response (PR), and total response (TR) respectively for
      the study and control groups. Our patients included in this study had a median
      follow up of 35 months and 33 months for study and control groups respectively.
      For this follow up, the disease-free survival, survival with disease and overall
      survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control
      groups respectively. There was an increase in early side-effects in the
      chemoradiation group but the difference was not significant. Because of the early
      side effects, treatment delays ensued in 7 patients (16.3%) and in 3 patients
      (7.3%) in the study and control groups respectively. There was no significant
      increase in the late treatment toxicities in both the groups.

PMID- 14716114
TI  - Stones associated renal pelvic malignancies.
AB  - BACKGROUND: The clinico-pathological characteristics of renal pelvic malignancies
      associated with stones were retrospectively analyzed. AIMS: The main objective
      was to define the biological behavior and prognostic factors for these
      malignancies. SETTINGS & DESIGN: The tumors were classified according to the
      pathological types. The clinical data, imaging features and pathological features
      were analyzed with relation to prognosis. MATERIAL AND METHODS: Eighteen cases of
      malignancies associated with stone disease were retrospectively studied. The
      institute review board permitted the study. RESULTS: High incidence (15/18) of
      squamous cell carcinoma (SCC) was noted. The prognosis in this group of patients
      was uniformly poor. The median survival time was 3.6 months in the SCC group, 7.5
      months in the Transitional Cell Carcinoma (TCC) group and 24 months in the
      Adenocarcinoma (AC) group. Infectious and systemic symptoms were noted in the
      majority of the patients. Preoperative Imaging techniques revealed tumor in only
      2 cases. Both underwent radical extirpation and the median survival is 18 months
      till date. In the other 16 patients, where the initial diagnosis was made only on
      histological analysis of incomplete nephrectomy specimens, the survival was 3.56
      months. All patients had prolonged history of staghorn stone disease with
      associated non-functioning kidney. We found that the main prognostic factor was
      the stage of the disease. CONCLUSIONS: Malignancies associated with stone disease
      have insidious onset of clinical symptoms and need a high degree of suspicion to
      identify them pre-operatively. The grave prognosis associated with incomplete
      excision makes it imperative to diagnose them earlier.

PMID- 14716115
TI  - Salvage chemotherapy and surgery for radio recurrent carcinoma glottis.
AB  - Chemoradiotherapy is increasingly used in advanced laryngeal cancers. Failures
      are generally managed by surgery. They include histologically confirmed recurrent
      or residual disease or a symptomatic life threatening treatment sequelae. Tumour
      recurrence or residivism can be managed by chemotherapy when radical surgery is
      either refused by the patient or if the general condition of the patient do not
      permit it. However surgery becomes inevitable when life threatening treatment
      sequelae like absolute pharyngo-oesophageal stricture and aspiration sets in.

PMID- 14716117
TI  - Primary squamous cell carcinoma of caecum.
AB  - Proximal to the anal canal, carcinomas composed in whole or in part of squamous
      epithelium are distinctly uncommon, accounting for 0.1 per cent of all colorectal
      carcinomas. Pure squamous cell carcinoma of the colorectum are extremely rare.
      Here we report a case of primary squamous cell carcinoma of the caecum in a 55
      year old lady from South India.

PMID- 14716116
TI  - Primary plasma cell leukemia occuring in the young.
AB  - Plasma Cell Leukemia (PCL) is a rare form of plasma cell dyscrasia. Plasma cell
      leukemia has two variants: the primary form presents de novo in patients with no
      previous history of multiple myeloma (MM); the secondary form consists of a
      leukemic transformation in a previously recognized MM. In contrast to myeloma,
      PCL has an aggressive course. Median age at presentation is usually above 50
      years. Here we report a case of primary PCL presenting at age of 21 years, which
      is extremely rare. She was treated with combination chemotherapy (VAD). Although
      she had a good response initially, later the disease progressed and she died 6
      months after the diagnosis.

PMID- 14716118
TI  - Solitary calvarial metastases: an unusual presentation of thoracic neuroblastoma.
AB  - A primary thoracic origin occurs only in 20% of neuroblastomas, and their
      classical presentation is mediastinal or cord compression. Skeletal metastases of
      neuroblastomas are characteristically multiple, and calvarial deposits usually
      show simultaneous involvement of orbit. Solitary metastases in neuroblastoma, is
      an unusual entity and its presentation as a large calvarial mass, especially from
      a thoracic primary, is rare. Furthermore, calvarial metastases are relatively
      uncommon in children compared to adults. We discuss the clinical, radiographic,
      CT features, and differential diagnosis of a large calvarial mass with sunray
      spiculation in a child, which was due to a solitary metastases from an occult
      thoracic neuroblastoma. The possibility of neuroblastoma presenting in this
      unique fashion and the importance of considering a chemosensitive tumor such as
      neuroblastoma in the differential diagnosis of a solitary calvarial mass in a
      child is highlighted by our report.

PMID- 14716119
TI  - Tobacco use among students in the eight North-eastern states of India.
AB  - OBJECTIVES: To obtain baseline information about prevalence of tobacco use among
      school children in eight states in the North-eastern part of India. MATERIAL AND
      METHODS: A two-stage probability sample of students in grades 8-10 corresponding
      to 13 to 15 years of age was selected in each state and surveyed through an
      anonymous, self-administered questionnaire. RESULTS: Among the sampled schools,
      the school response rate was 100% in all states except Tripura (92%) and
      Meghalaya (96%). Among the eligible students, over 80% participated in the
      survey. Among the respondents, the proportion of boys ranged between 50% to 55%.
      Ever tobacco users ranged from 75.3% (Mizoram) to 40.1% (Assam). Over 65% of
      users reported initiation at 10 years of age or earlier in all states except
      Mizoram (23.1%). The range of current tobacco use (any product) was 63%
      (Nagaland) to 36.1% (Assam). Current smokeless tobacco use ranged from 49.9%
      (Nagaland) to 25.3% (Assam). Mizoram reported the highest current smoking (34.5%,
      mainly cigarette) and Assam reported the lowest (19.7%, again mainly cigarette).
      Current smoking among girls (8.3% to 28.2%) was also quite high. Over half of
      current cigarette smokers (53.2% to 96.3%) and a high proportion of current
      smokeless tobacco users (38.5% to 80.8%) reported feeling like having tobacco
      first thing in the morning. Only about 20% of students reported having been
      taught in school about the dangers of tobacco use, except in Mizoram (around
      50%). Tobacco use by parents and close friends was positively associated with
      students' current tobacco use. CONCLUSIONS: Tobacco use including smoking was
      very high, even among girls, in all eight states in the North-eastern part of
      India. Signs of tobacco dependency were already visible in these students, more
      among those who smoked. In general schools did not educate students about the
      hazards of tobacco use.

PMID- 14716120
TI  - Sentinel lymph node biopsy in the management of breast cancer.
AB  - Sentinel node localization is the second most important development in this
      century after conservative lumpectomy for the treatment of early breast cancer.
      The sentinel node mapping is a new multidisciplinary approach for staging of
      axilla in an accurate and less morbid way as compared to axillary node
      dissection. Sentinel lymph node biopsy in patients with breast cancer has been
      adopted rapidly into clinical practice. The accuracy of sentinel lymph node
      biopsy is more than 95%, when performed meticulously (by an experienced
      multidisciplinary team) with proper patient selection. Sentinel lymph node biopsy
      is most widely used for both palpable and non-palpable T1 and T2 tumors. Recent
      studies show application of sentinel lymph node technique in patients with
      locally advanced breast cancer and after neoadjuvant chemotherapy. Therefore,
      sentinel lymph node biopsy technique has application in developing countries and
      other countries where screening for breast cancer is not common and most patients
      present relatively in advanced stage of the disease. Several aspects of the
      sentinel lymph node biopsy including technique, case selection, pathologic
      analysis and accuracy with supportive important studies published in the
      literature will be discussed in this review.

PMID- 14716121
TI  - Association of vitamin A, vitamin C and zinc with laryngeal cancer.
AB  - BACKGROUND: The incidence of the cancers of the oral cavity, pharynx, esophagus
      and larynx in different population groups of India is amongst the highest
      reported in Asian countries. There is evidence that high dietary carotenoids and
      vitamin C may possibly decrease the risk of laryngeal cancer. Limited data is
      available from India on the association between these micronutrients and the risk
      of laryngeal cancer. AIMS: To assess the levels of vitamin A, vitamin C and zinc
      in laryngeal cancer patients and healthy controls. SETTING AND DESIGN: A hospital
      based case- control study. MATERIAL AND METHODS: One hundred and fifty five
      laryngeal cancer patients and a control group of 155 healthy individuals
      constituted the study population. Individuals in the control group were
      individually matched with the patients for their age +/- 2 years, sex and place
      of residence. Venous blood was drawn from the cases and controls and estimations
      of vitamin A, zinc and vitamin C was done utilizing the standard procedures.
      STATISTICAL ANALYSIS USED: Paired 't' test to compare the mean serum levels of
      vitamin A and zinc and plasma vitamin C between laryngeal cancer patients and
      controls. Univariate logistic regression analysis to calculate the odds ratios
      and the confidence intervals. RESULTS: The mean serum vitamin A, zinc and plasma
      vitamin C levels were significantly lower in laryngeal cancer patients as
      compared to the controls. CONCLUSIONS: The findings of the present study
      indicated a strong association of these micronutrients with laryngeal cancer in
      the Indian population.

PMID- 14716122
TI  - Haematologic and immunophenotypic profile of acute myeloid leukemia: an
      experience of Tata Memorial Hospital.
AB  - OBJECTIVES: To study the hematologic and immunophenotypic profile of 260 cases of
      acute myeloid leukemia at diagnosis. MATERIAL AND METHODS: This is a
      retrospective analysis of 260 cases of AML diagnosed at our institution between
      1998 and 2000. Diagnosis was based on peripheral blood and bone marrow
      examination for morphology cytochemistry and immunophenotypic studies. SPSS
      software package, version 10, was used for statistical analysis. RESULTS: Seventy
      six percent of our cases were adults. The age of the patients ranged from one
      year to 78 years with a median age of 27.2 years. There were 187 males and 73
      females. The commonest FAB subtype, in both children and adults, was AML-M2. The
      highest WBC counts were seen in AML-M1 and the lowest in AML-M3 (10-97 x 10(9)/L,
      mean 53.8 x 10(9)/L). The mean values and range for hemoglobin was 6.8 gm/l (1.8
      gm/l to 9.2 gm/l), platelet count 63.3 x 10(9)/L (32-83 x 10(9)/L), peripheral
      blood blasts 41.4% (5 to 77%) and bone marrow blasts 57.6% (34-96%).
      Myeloperoxidase positivity was highest in the M1, M2 and M3 subtypes. CD13 and
      CD33 were the most useful markers in the diagnosis of AML. CD14 and CD36 were
      most often seen in monocytic (38%) and myelomonocytic (44%) leukemias. Lymphoid
      antigen expression was seen in 15% of cases. CD7 expression was the commonest
      (11%). CONCLUSION: AML accounted for 39.8% of all acute leukemias at this
      institution. The most common subtype was AML-M2. Myeloperoxidase stain was a
      useful tool in the diagnosis of myeloid leukemias. CD13 and CD33 were the most
      diagnostic myeloid markers.

PMID- 14716123
TI  - Primary chondrosarcoma of the breast: a case report.
AB  - Mammary sarcomas are uncommon tumors. Of these pure chondrosarcoma without any
      other area of epithelial or mesenchymal differentiation feature as even rarer.
      This excludes tumors like malignant cystosarcoma phyllodes and metaplastic
      carcinoma where malignant cartilaginous areas may be present. Further primary
      chondrosarcoma arises from breast stroma and not from underlying bone or
      cartilage. Only five cases of pure and primary chondrosarcoma have been reported
      so far. The sixth case is reported here.

PMID- 14716124
TI  - Maxillary mass as the presenting manifestation of papillary thyroid carcinoma.
AB  - A case of follicular variant of papillary thyroid carcinoma presenting with a
      right maxillary mass is described. This is perhaps the first instance of
      maxillary metastasis from papillary thyroid carcinoma.

PMID- 14716125
TI  - Alveolar soft part sarcoma: a unique tumor with disputed histogenesis.

PMID- 14716126
TI  - Tobacco use among school personnel in eight North-eastern states of India.
AB  - AIMS: To obtain baseline information about tobacco use prevalence, knowledge and
      attitude among school personnel in Eight North-eastern states of India (Assam,
      Arunachal Pradesh, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, and Tripura).
      MATERIAL AND METHODS: A sample of schools with probability proportional to the
      enrollment in grades 8-10. Anonymous self-administered questionnaire was used for
      all personnel working in the selected schools. RESULTS: The school response rate
      was 100% in all states except Meghalaya (96%) and Tripura (92%). Over 70% of
      school personnel participated in the survey, the proportion of men being 56%
      (Meghalaya) to 83% (Assam). The prevalence of daily smoking ranged from 25.9%
      (Mizoram) to 12.8% (Arunachal Pradesh) and of smokeless tobacco use from 57.8%
      (Mizoram) to 10.7% (Assam). Daily smoking among men and women was similar in five
      states but not in Arunachal Pradesh (men 15.0%, women 4.0%), Nagaland (men 18.7%,
      5.0%), and Tripura (men 18.6%, women 0.4%). In four states cigarette was the most
      prevalent form of smoking (range 41% to 55%) whereas in other four states it was
      bidi (range 34% to 53%). Although the number of women was small, cigarettes
      smoking was reported more among women than men in four states: Assam, Arunachal
      Pradesh, Manipur, and Nagaland. Over 50% of current smokeless tobacco users
      reported using betel quid in six states, except Mizoram (20%) and Sikkim (16%).
      CONCLUSION: Tobacco use among school personnel was high. High smoking rates
      reported by women were unexpected.

PMID- 14716127
TI  - A survey on risk factors associated with cervical cancer.
AB  - Carcinoma of the cervix is one of the leading malignancies in the developing
      countries including India. In view of this health care program might have to be
      redefined. Most of the data are available from the developed countries, which
      rely mainly on cytology screening on regular basis. This however may not be
      feasible in developing countries because of various constraints. Thus alternative
      approaches are needed based on risk reduction modalities. This article while
      dealing with the control approaches based on secondary prevention, reviews
      several risk factors associated with cervical cancer. The various articles were
      approached through Medline search including cross-references. The important life
      styles associated with cervical cancer and which are amenable to primary
      prevention strategies through health education, behavioral interventions,
      legislative approaches and modifying the health care seeking behavior were
      identified through the review process. These factors mainly pertain to early
      sexual debut, multiple sexual partners, menstrual hygiene and unprotected sex.
      Role of male partners has also been delineated in the process of cervical
      carcinogenesis. These factors are essentially conducive to the transmission of an
      etiological agent; the high-risk types human papillomaviruses, the more proximal
      cause in the web of causation. Barrier method of contraception and prophylactic
      vaccine in future could help to check the transmission of the virus. Role of
      smoking and oral contraceptives has also been discussed. Till the facilities for
      mass scale screening are developed in developing countries the primary prevention
      approaches could certainly help to check the incidence of the disease.

PMID- 14716128
TI  - Atypical squamous cells of undetermined significance: is it worthwhile to qualify
      them further?
AB  - BACKGROUND: In Bethesda System of reporting cervico-vaginal smears, the equivocal
      epithelial cell abnormalities have been categorised as "atypical squamous and
      glandular cells of undetermined significance" (ASCUS and AGUS). These
      abnormalities may harbour minor lesions attributed to mere inflammatory changes
      to potentially serious high grade lesions. It is recommended to further qualify
      these lesions according to whether they favor a reactive or a neoplastic outcome.
      AIMS: We undertook the present study to assess the significance of ASCUS
      qualifiers. MATERIAL AND METHODS: A total of 12071 women were screened for early
      detection of cancer cervix. The women with ASCUS diagnosis were further qualified
      as ASCUS favor reactive and ASCUS favor SIL (Squamous intraepithelial lesion)
      according the Bethesda 1991 system of reporting. ASCUS-reactive cases were
      followed up by a repeat smear examination and persistent ASCUS cases were taken
      up for colposcopy and biopsy if indicated. All ASCUS-SIL cases were taken up for
      immediate colposcopy. RESULTS: The pick up rate of high grade lesions was not
      significantly different (P=0.47; Chi square test) on the follow up of ASCUS
      reactive (2/222) and ASCUS-SIL (2/130) groups. The low grade lesions were picked
      up in 10/222 ASCUS-reactive and 58/130 in ASCUS-SIL, which was statistically
      significant (P < 0.001). CONCLUSIONS: The results of our study indicate that it
      is not worthwhile to qualify these lesions as majority of ASCUS-SIL also revealed
      only low grade epithelial which have a benign biological behaviour.

PMID- 14716129
TI  - How we performed chest wall reconstruction: analysis 31 cases.
AB  - OBJECTIVE: To see the results of patients who underwent chest wall resection and
      reconstruction (CWRR). SETTING AND DESIGN: Retrospective descriptional study.
      MATERIAL AND METHODS: We retrospectively reviewed all patients who underwent CWRR
      at Xingtai People's Hospital in China and B.P. Koirala Memorial Cancer Hospital
      in Nepal. A total of 31 patients were reviewed. Among them, 20 were male and 11
      female. The median age was 63 years. The indications for resection were primary
      chest wall tumor in 21 patients (67.7%), lung cancer with invasion of chest wall
      6 (19.4%), recurrence of breast cancer 2(6.3%), radiation necrosis 1(3.2%) and
      skin cancer 1(3.2%). RESULTS: The mean number of rib resected was 3.6 ribs, which
      induced a mean defect of 97.1 cm2. Concomitant resection was done in 13 patients,
      including lung resection 10, partial resection of diaphragm 2, and partial
      sternectomy 1. Seven patients underwent soft tissue reconstruction (STR) alone
      and 5 patients skeletal reconstruction (SR) alone. Simultaneous SR and STR were
      performed in 19 patients. Three patients (9.7%) developed postoperative
      complications. The median survival period was 22 months. CONCLUSION: Primary
      chest wall tumor and lung cancer invading chest wall are the most common diseases
      indicating CWRR. Simultaneous bony and soft tissue reconstruction was reliable
      for chest wall reconstruction in most cases and prevents postoperative
      complications.

PMID- 14716130
TI  - Colloid cyst of the third ventricle: a cause of sudden death in a child.
AB  - Colloid cyst is a rare benign intracranial neoplasm, commonly located in the
      third ventricle. Though headache and visual symptoms are classical, the patients
      may present with sudden neurological deterioration. We present a ten-year-old
      male child who presented with sudden neurological deterioration due to colloid
      cyst of the third ventricle resulting in death. The child had intermittent
      headache for three months, for which medical attention was not sought. This
      report details the case and a short review of the condition is presented (with
      emphasis on the clinical features and importance of early diagnosis). Management
      (including surgical methods and conservative treatment) of third ventricle
      colloid cysts is briefly reviewed.

PMID- 14716131
TI  - Mucoepidermoid carcinoma of the bronchus: is conservative surgery always
      justified?
AB  - A case of mucoepidermoid carcinoma of the bronchus in a 7-year-old boy is
      reported. The patient underwent right pneumonectomy. Histologically, the tumor
      was a low-grade muco-epidermoid carcinoma arising from the bronchus with lymph
      node metastasis in the drainage area. Presence of lymph node metastasis in this
      low-grade tumor suggests the possibility of early progression of disease in what
      has until now been considered a very slow growing tumor. Aggressive surgery may
      be necessary in these situations.

PMID- 14716132
TI  - Carcinoma of esophagus with unusual metastasis to gingiva and phalanx.

PMID- 14716133
TI  - [Towards new therapy strategies].

PMID- 14716134
TI  - [Perspectives in oncology].

PMID- 14716135
TI  - [Palliative therapy of breast cancer].
AB  - Metastatic breast cancer is considered an incurable disease. The choice of drug
      or drug combination in palliative therapy is determined by the subjective
      symptoms of the patient and by the more objective parameters age and general
      health status, localization of metastases and aggressiveness of the disease,
      which is described by the necessity to achieve remission. The relation between
      the effectiveness aimed for and the subjective quality of life is described by
      the term 'therapeutic index'. With receptor-positive tumours and under low
      remission pressure, endocrine therapy is the method of choice when considering
      sustaining the quality of life--here aromatase inhibitors have replaced the
      former gold standard anti-estrogen tamoxifen. With receptor-negative tumors or
      under high remission pressure the therapy decision is far more difficult. The
      cytostatic therapy can be performed as mono- or polychemotherapy. In both cases
      taxanes show a higher effectiveness when compared to standard therapies, with
      Docetaxel giving the highest response rate and (as shown in a recent Cochrane
      analysis) increasing overall survival with a HR of 0.88. We describe taxane
      containing therapy regimes in the context of modern therapy options. Current data
      presented by 4 chosen studies are described, as well as AGO recommendations on
      palliative therapy.

PMID- 14716136
TI  - [Current status and perspectives of chemotherapy for anthracycline-pretreated
      breast cancer].
AB  - Randomized trials performed in anthracycline-pretreated breast cancer patients
      have demonstrated good activity of taxane-based regimens. In a face to face
      comparison, single-agent docetaxel proved to be significantly more effective than
      paclitaxel. Treatment with docetaxel was also associated with an increased
      incidence of grade grade-3/4 toxicities in this trial. Antitumor activity of
      taxane-based combination regimens was clearly superior to single-agent therapy in
      two trials. As anticipated, treatment-associated toxicity was greater with
      combination regimens, but this did not affect quality of life.

PMID- 14716137
TI  - [Adjuvant chemotherapy in primary breast cancer].
AB  - Adjuvant chemotherapy reduces the relative risk of relapse by about 25%-
      independent of the nodal status. Anthracycline-containing regimens are considered
      standard for adjuvant chemotherapy. In single studies, superiority to CMF has
      only been shown for anthracycline-containing polychemotherapies with at least
      three substances or a sequential anthracycline-CMF therapy. Recent data show that
      adding taxanes to anthracycline-containing regimens may lead to significant
      survival advantages. Based on trial results published so far, taxanes are a valid
      adjuvant therapy option in node-positive breast cancer. In Germany, their optimal
      use is currently being evaluated in several clinical trials (i.e. NNBC-3, ECDoc,
      ADEBAR). Up-to-date evidence-based therapy recommendations for adjuvant
      chemotherapy can be found in the S2 guidelines of the working group on
      gynecological oncology (AGO) expert panel 'breast' (www.agoonline. de).

PMID- 14716138
TI  - [Taxanes in primary systemic treatment of breast cancer].
AB  - Primary systemic treatment today represents a new option for patients with
      operable breast cancer and is equally effective as conventional adjuvant
      chemotherapy. Improving surgical options is the most important indication for
      choosing this approach. The highest chance for breast conserving surgery can be
      obtained when a sequence of adriamycin and cyclophosphamide (AC) is followed by
      docetaxel. This has been shown in the Geparduo and NSABP-B27 trial. New
      approaches are considering individual tailoring of treatment according to either
      early response of the primary breast tumor (Gepartrio) or pharmacogenetic testing
      on the tumor tissue.

PMID- 14716139
TI  - [Docetaxel (Taxotere) as first-line therapy of advanced non-small cell lung
      cancer (NSCLC)].
AB  - Taxotere as a 'stabilizing antitubuline' and a second-generation Taxan has anti
      tumor activity in a variety of solid neoplasms. In NSCLC Taxotere has shown
      encouraging response rates across a range of phase-II studies, and phase-III
      trials have confirmed its effectiveness in pretreated and chemotherapy-naive
      patients. Single agent Taxotere has shown that it can significantly improve both
      survival and quality of life when compared to either best supportive care or
      standard chemotherapy in previously treated patients. Therefore, it is considered
      standard for NSCLC second-line chemotherapy. Taxotere has also been evaluated in
      combination with platinum-compounds and non-platinum-based drugs for first-line
      treatment of NSCLC. The results recently published from a phase-III registration
      trial (TAX 326) have shown that the overall survival among patients randomized to
      receive Taxotere/Cisplatin was better than that among patients treated with
      Vinorelbin/Cisplatin and similar compared to Vinorelbin/Cisplatin for those
      patients who received Taxotere/Carboplatin. Given concomitantly or sequentially
      with non-platinum-based compounds (i.e. Gemcitabine, Vinorelbine) Taxotere has
      also shown promising activity in randomized studies and may offer advantages for
      patients not eligible to receive platinum-based compounds.

PMID- 14716140
TI  - [Docetaxel in neoadjuvant therapy of early-stage non-small cell carcinoma].
AB  - The combination of docetaxel and cisplatin is one of the standard chemotherapy
      regimens which has been shown to improve survival and quality of life in patients
      with advanced non-small cell lung cancer (NSCLC). Docetaxel has therefore been
      administered by several groups in the neoadjuvant setting in stage-III disease.
      In combination with cisplatin, the response rate, the complete resection rate and
      the pathological response rate were similar as in other regimens, postoperative
      morbidity and mortality, however, seemed reduced when compared with combinations
      including mitomycin C. Furthermore, there was an association of the chemotherapy
      activity in mediastinal lymph nodes of patients with a NSCLC (stage IIIA) and
      overall survival. Based on these results, the cytostatic combination of
      docetaxel/cisplatin has been chosen for further use in large randomized studies.

PMID- 14716141
TI  - [Significance of docetaxel in the chemotherapy of hormone-refractory prostate
      cancer].
AB  - Docetaxel (Taxotere) is a taxoid derived from the European yew tree, taxus
      baccata. In 4 phase-II studies docetaxel has important single agent activity with
      an overall prostate-specific antigen response rate of 42% in hormone refractory
      prostate cancer. Other phase-II studies suggest that the addition of estramustine
      to docetaxel results in a higher response rate but also in an increased toxicity.
      At present Docetaxel with and without estramustine is being evaluated in phase
      III studies that will provide definitive information about its role in hormone
      refractory prostate cancer.

PMID- 14716142
TI  - [Palliative therapy of colorectal cancer].
AB  - Systemic chemotherapy has a key role in the palliative treatment of patients with
      metastatic colorectal cancer. Compared to best supportive care, 5-fluorouracil (5
      FU)-based therapy prolongs survival and improves quality of life. 5-FU continuous
      infusion modulated by Leukovorin (LV) is the optimal basis for a combination
      therapy with irinotecan or oxaliplatin. Randomized trials investigating the role
      of irinotecan in combination with 5-FU/LV relative to 5-FU/LV alone demonstrated
      a significant improvement in the response rate, progression free survival and
      overall survival. Randomized studies using oxaliplatin/ 5-FU/LV vs. FU/LV alone
      resulted in a higher response rate and longer progression-free survival while the
      overall survival was not significantly different. Today, all patients should
      receive combination treatment in first line and should be offered all active
      compounds during the course of their disease. Hereby, median survival times of
      more than 20 months are achievable. The use of oral fluoropyrimidines as a
      substitute of infusional 5-FU in combination with irinotecan or oxaliplatin is
      promising and subject of clinical trials. Monoclonal antibodies directed against
      the EGF-receptor or against VEGF have demonstrated interesting results and may be
      a treatment option in the future.

PMID- 14716144
TI  - [New chemotherapeutic options in advanced gastric cancer].
AB  - Over the last years the therapeutic possibilities for advanced gastric cancer
      have significantly increased. Here we discuss the new chemotherapeutic options
      and the existing results in palliative therapy.

PMID- 14716143
TI  - [Chemotherapy of advanced colorectal carcinoma: treatment options for elderly
      patients].
AB  - At present, approximately 70% of patients with colorectal cancer are older than
      65 years at the time of diagnosis. This cancer population needs to be thoroughly
      assessed for the benefits of adjuvant or palliative chemotherapy. A comprehensive
      geriatric assessment may allow subdividing the population of elderly cancer
      patients into three groups thus helping to guide treatment decisions. It has been
      demonstrated that the use of 5-fluorouracil (5-FU) based adjuvant chemotherapy in
      elderly patients effectively reduces mortality and can be applied with acceptable
      toxicity. Systemic chemotherapy for patients with metastatic disease will have
      palliative effects and lead to prolongation of survival. While several data exist
      for the combination of 5-FU and folinic acid in elderly patients, data about
      combination chemotherapy with 5-FU and new drugs such as irinotecan or
      oxaliplatin is still limited. There appears to be an age-associated increase in
      drug-specific toxicity when these agents are used. However, for carefully
      selected elderly patients receiving adequate monitoring throughout therapy these
      new treatment approaches can be made available. Clinical studies also indicate
      that treatment effectiveness in selected elderly patients is comparable to that
      observed in the younger patient population. Future trials need to further
      redefine treatment strategies in elderly patients with colorectal cancer.

PMID- 14716145
TI  - [Proapoptotic therapy with oblimersen (bcl-2 antisense oligonucleotide)--review
      of preclinical and clinical results].
AB  - The regulation of apoptosis is an important potential target for anticancer
      therapy. The mitochondrial Bcl-2 protein inhibits apoptosis and is therefore an
      important mediator of resistance to treatment with traditional cytotoxic
      chemotherapy, radiotherapy and monoclonal antibody therapy. Oblimersen
      (Genasense, Aventis Pharmaceuticals / Genta Inc) is a 18mer antisense
      oligonucleotide (ASO), which specifically binds to the first 6 codons of the
      human bcl-2 mRNA, resulting in degradation and destruction of the mRNA by RNAse
      H. Subsequently there is a significant decrease of bcl-2 translation. A growing
      number of preclinical and clinical studies suggests that the combination of
      cytotoxic therapy with Oblimersen results in synergistic anticancer efficacy in
      many hematologic and solid tumors. Due to its low toxicity profile, oblimersen is
      an ideal combination partner with conventional chemotherapy. Three randomized
      phase-III trials (malignant melanoma, chronic lymphocytic leukemia, multiple
      myeloma) have recently finished recruitment. The results of these studies will be
      available by the end of 2003. Based on preclinical data, a lot of nonrandomized
      phase-II studies on several different tumor types like AML, CML, NHL, prostate
      cancer and breast cancer are underway. The manipulation of proapoptotic and
      antiapoptotic factors in favor of proapoptotic factors by inhibition of the bcl-2
      protein translation in order to enhance the efficacy of anticancer treatments
      represents a promising new treatment concept in oncology.

PMID- 14716146
TI  - [Novel molecular approaches in the therapy of advanced colorectal carcinoma].
AB  - Therapeutic options for patients with metastatic colorectal cancer have clearly
      improved during the last years. The regular use of irinotecan and oxaliplatin in
      first- and second-line treatment led to a clear improvement of median overall
      survival time. For the first time a new therapeutic concept--the inhibition of
      tumor angiogenesis--has been realized for clinical use by combining the anti-VEGF
      monoclonal antibody bevacizumab with an irinotecan-based first-line therapy. The
      monoclonal antibody cetuximab, targeted against EGFR, offers another new and very
      effective therapeutic option to patients with advanced irinotecan-refractory
      colorectal cancer--even those who are already pretreated with oxaliplatin.
      Further clinical studies are going to evaluate the future role of these new
      molecular treatment options as part of those therapeutic possibilities which are
      already available and established for the treatment of colorectal cancer patients
      with advanced disease (such as the optimal sequencing, the role of orale
      fluoropyrimidine-based combination therapy with cetuximab or bevacizumab).

PMID- 14716147
TI  - Reproductive biology of the slender loris (Loris lydekkerianus lydekkerianus).
AB  - The slender loris (Loris lydekkerianus lydekkerianus), a nocturnal prosimian, was
      studied for 21 months in its natural habitat of scrub jungle in Dindigul, south
      India. Here we report on its reproductive biology. Identified and unidentified
      lorises were observed for a total of 2,656 h. Reproductive seasonality was seen,
      with births and oestrus observed to be highest in April-June and October
      December. The mating system was promiscuous with 1 female mating successively
      with 3-4 males. A gestation period of 5.5 months and an inter-birth interval of 7
      months were recorded. Adult females had a reproductive potential of 4 infants per
      year. The findings presented in this paper constitute the first information on
      the life history parameters of wild slender lorises.

PMID- 14716148
TI  - Twinning in tufted capuchins (Cebus apella): rate, survivorship, and weight gain.
AB  - We calculated the rate of twinning across four captive collections of tufted
      capuchins (Cebus apella) to be 2.4%. This rate contrast with previous reports
      that twinning in tufted capuchins is rare. Additionally, we present data on the
      survival and weight gain of twins in this species as compared to singletons.
      Twins face their greatest risk of mortality on or before the first day of life,
      when 45% will die compared to 16% of singletons. After the first day of life,
      twins and singletons demonstrate comparable survival rates. This, in conjunction
      with the finding that at no time during the first year of life do twins and
      singletons differ significantly in their weights, suggests that twinning is a
      viable reproductive form for these animals, especially in the captive setting
      where nutritional demands are met.

PMID- 14716149
TI  - Genetic comparison of two populations of Hapalemur simus inferred from D-loop
      mitochondrial DNA sequences.

PMID- 14716150
TI  - Which nests to choose: collecting shed hairs from wild orang-utans.

PMID- 14716151
TI  - Temporary absence and dispersal in Phayre's leaf monkeys (Trachypithecus
      phayrei).

PMID- 14716152
TI  - Variable grooming behaviours in wild chimpanzees.

PMID- 14716153
TI  - Adaptation of a captive-raised gibbon to the wild.

PMID- 14716155
TI  - Reduction, regrowth, and de novo formation of abdominal adhesions after
      laparoscopic adhesiolysis: a prospective analysis.
AB  - AIM: A significant reduction of abdominal adhesions at second-look relaparoscopy
      after adhesiolysis in patients with chronic abdominal pain. METHODS: 368 patients
      underwent laparoscopic adhesiolysis because of chronic abdominal pain. Regrowth
      and de novo abdominal adhesions were determined in a qualitative and quantitative
      way in 24 patients who underwent a second-look re-laparoscopy because of
      recurrent pain after a mean period of 16 months after the first laparoscopic
      adhesiolysis. Reduction of incidence, extent, type, and severity of abdominal
      adhesions between organs and abdominal wall and de novo adhesion formation were
      determined. RESULTS: Incidence (40 vs. 26), extent, type, and severity of
      abdominal adhesions between organs and abdominal wall are significantly reduced
      after laparoscopic adhesiolysis. After adhesiolysis of adhesions between organs
      themselves, no significant reduction could be demonstrated (incidence 40 vs. 32).
      De novo adhesions were present in 5 (5/24) patients. CONCLUSION: Laparoscopic
      adhesiolysis results in a significant reduction of adhesions between organs and
      abdominal wall, despite the occurrence of de novo adhesions in about 20% of the
      patients.

PMID- 14716157
TI  - Patient-controlled analgesia for sickle cell pain crisis in a pediatric emergency
      department.
AB  - OBJECTIVE: To determine whether a protocol to start patient-controlled analgesia
      (PCA) in the emergency department (ED-PCA) would shorten the length of time
      between narcotic bolus doses and PCA initiation as compared with standard
      inpatient initiation of PCA (IP-PCA). Also, to compare patient satisfaction and
      inpatient length of stay for the 2 groups. METHODS: To improve care, we developed
      a protocol to institute ED-PCA after an initial bolus dose of narcotics. This was
      a nonrandomized pilot study. Patient records were reviewed for location of PCA
      initiation, time from narcotic bolus to initiation of PCA, and length of stay. A
      brief patient/parent satisfaction survey was collected. RESULTS: Sixty-nine
      records were reviewed. Patients treated using the protocol had initiation of PCA
      therapy within 35 +/- 7 minutes from the last bolus narcotic dose in the
      emergency department versus 211 +/- 17 minutes for nonprotocol patients. Forty
      eight of 50 patient surveys indicated preference for starting ED-PCA; 2 did not
      have a preference. No complications were identified in either group. CONCLUSIONS:
      A protocol to initiate PCA for sickle cell patients in a pediatric emergency
      department shortened the time of its initiation and was preferred by patients.

PMID- 14716158
TI  - Secondary triage of the injured pediatric patient within the trauma center:
      support for a selective resource-sparing two-stage system.
AB  - OBJECTIVES: While it is generally agreed that pediatric trauma patients exposed
      to high-risk injury mechanisms should be sent to trauma centers, many patients
      seen with full trauma alerts are determined to have minimal injury. The purpose
      of this study was to develop and test a clinical tool to safely triage a group of
      pediatric trauma patients for initial evaluation by the emergency department (ED)
      within the trauma center. METHODS: The pediatric trauma score (PTS) was used as
      the basis for development of a simplified, user-friendly assessment tool called
      the modified pediatric trauma score (mPTS). It used basic physiologic and
      anatomic signs identified at ED triage. This tool was retrospectively tested
      against the outcomes of 1112 pediatric trauma patients as determined by their
      final injury severity scores (ISS) and the need for urgent interventions.
      RESULTS: Our tool would have triaged 58% of patients to ED preevaluaton resulting
      in significant resource savings. Concurrently, 99% of patients with an ISS
      greater than 10 and all patients who needed urgent interventions would have
      remained full trauma alert patients. The positive predictive value of our tool
      was only 0.32. indicating that a safe level of overtriage was maintained.
      CONCLUSION: This study serves as further support for the concept of multitiered
      triage systems within trauma centers. In such settings, initial evaluations of
      select pediatric patients can be safely performed by emergency medicine staff
      with deferral of full trauma team alerts.

PMID- 14716159
TI  - The educational experience of pediatric emergency medicine fellows in the use and
      application of procedural sedation/analgesia.
AB  - OBJECTIVES: The purpose of this study is to describe the clinical and educational
      experience provided to the pediatric emergency medicine (PEM) fellows in
      procedural sedation/analgesia during their course of training. METHODS: A
      nonanonymous survey was completed by the program director of each Accreditation
      Council for Graduate Medical Education (ACGME)-accredited PEM fellowship program
      listed in the 2001 to 2002 Graduate Medical Education Directory. Information
      relating to program demographics, agents available for use in the emergency
      department (ED), and the educational opportunities offered to trainees was
      sought. RESULTS: Each of the 32 ACGME-accredited programs completed the survey.
      Thirty programs report using procedural sedation and analgesia (PSA) to
      facilitate the completion of nonpainful and 32 programs to facilitate the
      completion of painful procedures in the ED. Twenty-nine programs (92%) permit
      their fellows to provide PSA independently after meeting credentialing criteria
      at their institution. Formal didactic sessions, direct supervision of procedures,
      and dedicated journal clubs were the 3 most frequently cited educational methods
      reported. The educational method chosen was not predicted by the ED type, the
      size of the training program, or by the volume of patients evaluated in the ED.
      Twelve program directors report their belief that a minimum number of procedures
      should be completed prior to completion of the training program. CONCLUSION:
      There is wide variation in the educational methods used by PEM fellowship
      training programs in procedural sedation/analgesia.

PMID- 14716160
TI  - Pediatric observation status beds on an inpatient unit: an integrated care model.
AB  - OBJECTIVES: Describe the usage of observation status (OS) beds on a pediatric
      inpatient unit and identify diagnoses likely to be successfully discharged
      compared to those requiring formal inpatient admission. METHODS: Retrospective
      chart review of all patients (0-18 years) transferred to pediatric OS beds from
      the emergency department (ED) between April 1, 1997 and April 30, 1999. Outcome
      measures consisted of time interval between ED triage and arrival to an OS bed,
      total hours in observation, and need for admission or transfer. Using relative
      risk (RR), we compared admission rates for the 4 most common diagnoses. RESULTS:
      We studied 800 transfers to pediatric OS beds. Asthma (27%),
      gastroenteritis/dehydration (16%), infectious disease (12%), and bronchiolitis
      (9%) were the 4 most common diagnoses. There were 597 patients (75%) successfully
      discharged from observation and 174 (22%) required inpatient admission. Seventeen
      patients (2%) were transferred to a psychiatric facility and 12 patients (1%)
      were transferred to a tertiary care center for further evaluation and treatment.
      Compared to gastroenteritis/dehydration, patients with asthma were just as likely
      to be admitted/transferred (RR 1.05, 95% CI, 0.87-1.27), those with an infectious
      disease were 1.3 times more likely to be admitted/transferred (RR 1.35, 95% CI,
      1.0-1.83), and those with bronchiolitis were 2 times more likely to be
      admitted/transferred (RR 1.92, 95% CI, 1.34-2.74). CONCLUSIONS: We describe the
      usage of OS beds in a community hospital that we believe can be a successful
      model for the care of pediatric patients. Future studies are needed to delineate
      the clinical characteristics of patients that would benefit from this care
      delivery model.

PMID- 14716161
TI  - Difficulty in obtaining peak expiratory flow measurements in children with acute
      asthma.
AB  - OBJECTIVE: To determine the frequency with which children >or=6 years with acute
      asthma can perform peak expiratory flow rate measurements (PEFR) in an emergency
      department (ED). DESIGN/METHODS: Data were obtained from a prospective cohort
      study of children with acute asthma. All children (age 2-18 years old) treated in
      an urban pediatric ED for an acute exacerbation during randomly selected days
      over a 12-month period were prospectively evaluated. According to treatment
      protocols, PEFR was to be measured in all children age 6 years and older before
      therapy and after each treatment with inhaled bronchodilators. Registered
      respiratory therapists obtained PEFR and evaluated whether patients were able to
      perform the maneuver adequately. RESULTS: Four hundred and fifty-six children, 6
      to 18 years old (median 10 years), were enrolled; 291 (64%) had PEFR measured at
      least once. Of those in whom PEFR was attempted at least once, only 190 (65%)
      were able to perform adequately. At the start of therapy, 54% (142/262) were able
      to perform PEFR. Of the 120 who were unable to perform initially, 76 had another
      attempt at the end of the ED treatment, and 55 (72%) were still unable to
      perform. A total of 149 patients had attempts at PEFR both at the start and end
      of treatment, of these, only 71 (48%) provided valid information on both
      attempts. Patients unable to perform PEFR were younger (mean +/- SD = 8.7 +/- 2.8
      years) than those who were able to perform successfully (11.2 +/- 3.2 years) and
      those with no attempts (10.0 +/- 3.4 years). Children admitted to the hospital
      were more likely to be unable to perform PEFR (58/126 = 46%) than those
      discharged from the ED (43/330 = 13%, P < 0.0001). CONCLUSION: Adequate PEFR
      measurements are difficult to obtain in children with acute asthma. Treatment and
      research protocols cannot rely exclusively on PEFR for evaluation of severity.

PMID- 14716162
TI  - Traumatic dissection of the internal carotid artery.
AB  - We present the case of an 11-year-old male who had a dissection of his left
      internal carotid artery following a rather innocuous mechanism of injury.
      Although this phenomenon is documented in the medical literature, it remains a
      relatively rare event following blunt injury to the head and neck (0.3%
      occurrence rate in 1 study spanning 7 years). (Despite its rarity, it remains an
      important cause of cerebrovascular accidents in children. 2) Children presenting
      with gross neurologic abnormalities following blunt trauma to the head or neck
      should be considered to have sustained injury to the carotid arteries until
      proven otherwise.

PMID- 14716164
TI  - Out-of-hospital cardiopulmonary arrest in children with croup.
AB  - Viral laryngotracheobronchitis is a ubiquitous infectious process that has not
      caused significant mortality in the past 20 years. Bacterial tracheitis and
      pneumonia can complicate viral laryngotracheobronchitis and markedly increase the
      risk of bad outcome. Even uncomplicated, properly managed, viral
      laryngotracheobronchitis can occasionally result in death, particularly in the
      infant age group.

PMID- 14716163
TI  - Visual, tactile, and phobic hallucinations: recognition and management in the
      emergency department.
AB  - OBJECTIVES: The purposes of this case series are to review the acute
      manifestations of hallucinatory phenomenon in young children, with a focus on
      visual, tactile, and phobic hallucinations (VTPH) as an important part of the
      differential diagnosis; and to describe 10 children who presented to the
      Children's National Medical Center Emergency Department (CNMC ED) with VTPH.
      METHODS: The medical records of children identified with VTPH who were evaluated
      during a 20-month period in 1998 to 1999 were reviewed. The diagnosis was
      established if the hallucinations were well documented as being anxiety-related,
      not auditory, and with no evidence of underlying organic etiology. All cases were
      initially screened in the emergency department. Demographic information included
      age, gender, duration, and description of symptoms, stressors, family psychiatric
      history, and outpatient treatment. RESULTS: Ten children with this disorder were
      encountered. VTPH can be differentiated from other causes of hallucinations in
      that the children are preschool to young school age; their hallucinations are
      tactile and visual, presenting at night; and symptoms are anxiety-based but short
      lived. When toxins, drug reactions, central nervous system, and febrile
      etiologies are ruled out, timely consultation with the psychiatry team can
      eliminate costly and time-consuming procedures and avoid further emotional
      distress for the child and family. CONCLUSIONS: VTPH is a more commonly occurring
      disorder than previously reported in the pediatric emergency medicine literature.
      Emergency physicians who recognize the characteristics of this diagnosis are
      encouraged to seek psychiatric consultation rather than performing unnecessary
      and costly diagnostic tests.

PMID- 14716165
TI  - Emergency department presentation of biotinidase deficiency: fulminant sepsis in
      a 4-year-old Hispanic male.

PMID- 14716166
TI  - Conservative management of large avulsions of the lip and local landmarks.
AB  - Large lip avulsion injuries that involve significant tissue loss to the lip
      vermilion and other local landmarks can often pose a surgical dilemma for the
      reconstructive surgeon. Immediate reconstruction of these injuries are frequently
      performed using local flaps and adjacent tissue transfer to close the defect, but
      these repairs frequently suffer from the unfortunate consequence of increased
      associated scarring and further permanent distortion of the local anatomy. We
      present 2 patients sustaining dog bite injuries associated with extensive
      traumatic tissue loss to the lip vermilion and other local landmarks. These
      patients were treated conservatively with excellent functional and cosmetic
      results. A single minor surgical revision of 1 patient's cupid's bow was
      performed 1 year after injury. In cases of significant traumatic avulsion
      involving the lip vermilion and the perioral composite soft tissue, even with
      injuries including delicate anatomic landmarks, healing by secondary intention
      can be instituted as the initial treatment of choice in younger patients, often
      providing optimal results.

PMID- 14716167
TI  - Case records of Wright State University: unexplained, recurrent abdominal pain.

PMID- 14716168
TI  - Tetanus in children.

PMID- 14716169
TI  - Vomiting, diarrhea and--oh! oh! what is that?

PMID- 14716170
TI  - Pain and sedation.

PMID- 14716171
TI  - Pediatric emergency medicine: legal briefs.

PMID- 14716172
TI  - HIPAA compliance efforts.
AB  - OBJECTIVES: Identify the regulations from the Health Insurance Portability and
      Accountability Act (HIPAA) that impact the emergency department. Describe
      processes that demonstrate compliance with the security and privacy regulations
      that pertain to protected health information. Identify the consequences of
      noncompliance to this congressional mandate. METHODS: A review of the literature
      was conducted to extract the effects of the legislation on emergency services.
      Since the inception of the law in 1996, additional regulatory requirements have
      been added to the protection of protected health information. Concomitantly,
      practice changes are conducive to emergency department's compliance with these
      regulatory mandates. RESULTS: HIPPA encompasses 6 components in the regulations
      that must be addressed. Of these, most organizations focus on the greatest areas
      of risk, which include the transmission of electronic data and the security and
      privacy components. To avoid financial penalties and imprisonment, facilities
      must demonstrate and adhere to the regulations outlined. Verification of
      compliance could occur through random unannounced visits by the Department of
      Health and Human Services, Office of Civil Rights, or through health information
      privacy complaints filed against the individual or the organization. CONCLUSIONS:
      A sharing of best practices and benchmarking could contribute to organizational
      savings and improve productivity if facilities were forthcoming in describing how
      they demonstrate compliance. As interpretations and applications of the law are
      modified, practice changes will also occur. Since each facility is held to the
      same standard, it behooves one to provide mutual support so as not to begin the
      process from its genesis.

PMID- 14716173
TI  - ECGs in the ED.

PMID- 14716174
TI  - Menopause and CME.

PMID- 14716175
TI  - Treatment of vasomotor symptoms during perimenopause.

PMID- 14716176
TI  - Predicting time to menopause using self-reported menstrual data.

PMID- 14716177
TI  - Are all estrogens created equal?

PMID- 14716179
TI  - Treatment of menopause-associated vasomotor symptoms: position statement of The
      North American Menopause Society.
AB  - OBJECTIVE: To create an evidence-based position statement regarding the treatment
      of vasomotor symptoms associated with menopause. DESIGN: The North American
      Menopause Society (NAMS) enlisted clinicians and researchers acknowledged to be
      experts in the field of menopause-associated vasomotor symptoms to review the
      evidence obtained from the medical literature and develop a document for final
      approval by the NAMS Board of Trustees. RESULTS: For mild hot flashes, lifestyle
      related strategies such as keeping the core body temperature cool, participating
      in regular exercise, and using paced respiration have shown some efficacy without
      adverse effects. Among nonprescription remedies, clinical trial results are
      insufficient to either support or refute efficacy for soy foods and isoflavone
      supplements (from either soy or red clover), black cohosh, or vitamin E; however,
      no serious side effects have been associated with short-term use of these
      therapies. Single clinical trials have found no benefit for dong quai, evening
      primrose oil, ginseng, a Chinese herbal mixture, acupuncture, or magnet therapy.
      Few data support the efficacy of topical progesterone cream; safety concerns
      should be the same as for other progestogen preparations. No clinical trials have
      been conducted on the use of licorice for hot flashes. Among nonhormonal
      prescription options, the antidepressants venlafaxine, paroxetine, and fluoxetine
      and the anticonvulsant gabapentin have demonstrated some efficacy for treating
      hot flashes and were well tolerated. Two antihypertensive agents, clonidine and
      methyldopa, have shown modest efficacy but with a relatively high rate of adverse
      effects. For moderate to severe hot flashes, systemic estrogen therapy, either
      alone (ET) or combined with progestogen (EPT) or in the form of estrogen
      progestin oral contraceptives, has been shown to significantly reduce hot flash
      frequency and severity. Clinical trials have associated ET/EPT with adverse
      effects, including breast cancer, stroke, and thromboembolism. Several
      progestogens (both oral and intramuscular formulations) have shown efficacy in
      treating hot flashes, including women with a history of breast cancer, although
      no definitive data are available on long-term safety in these women. CONCLUSIONS:
      In women who need relief for mild vasomotor symptoms, NAMS recommends first
      considering lifestyle changes, either alone or combined with a nonprescription
      remedy, such as dietary isoflavones, black cohosh, or vitamin E. Prescription
      systemic estrogen-containing products remain the therapeutic standard for
      moderate to severe menopause-related hot flashes. Recommended options for women
      with concerns or contraindications relating to estrogen-containing treatments
      include prescription progestogens, venlafaxine, paroxetine, fluoxetine, or
      gabapentin. Clinicians are advised to enlist women's participation in decision
      making when weighing the benefits, harms, and scientific uncertainties of
      therapeutic options. Regardless of the management strategy adopted, treatment
      should be periodically reassessed as menopause-related vasomotor symptoms will
      abate over time without any intervention in most women.

PMID- 14716180
TI  - Low-dose transdermal estradiol for symptomatic perimenopause.
AB  - OBJECTIVE: To determine whether low-dose transdermal estrogen therapy is
      associated with a reduction in vasomotor symptoms in women who continue to have
      menstrual cycles. DESIGN: An open-label, observational evaluation conducted over
      12 months in 22 consecutive perimenopausal women with vasomotor symptoms.
      RESULTS: Improvement in vasomotor symptoms was reported by 16 (73%) of women
      evaluated. Of responders, 11 characterized symptom relief as complete and 6 as
      moderate. Fifteen (68%) of the women remained on transdermal estrogen at 12
      months. No adverse health-related events were attributed to estrogen therapy.
      CONCLUSION: Low-dose transdermal estrogen is well tolerated and was associated
      with a reduction in complaints of vasomotor symptoms before menopause. The steady
      state pharmacokinetics of transdermal delivery of unopposed estrogen may be
      advantageous in a population sensitive to fluctuations in circulating hormone
      levels.

PMID- 14716181
TI  - Menopausal transition: predicting time to menopause for women 44 years or older
      from simple questions on menstrual variability.
AB  - OBJECTIVE: To assess whether menstrual variability predicts time to menopause.
      DESIGN: Analyses drew on 326 menstruating women, aged 44 to 56, who were followed
      until they reached menopause or the study ended. The women provided data on their
      menstrual characteristics at intake. We evaluated the utility of six definitions
      of menstrual variability for predicting time to ascertained menopause (final
      menstrual period + 12 months): (1) more than 90 days since the most recent
      menstrual period (n = 20); (2) 60 or more days of amenorrhea during the previous
      year (n = 71); (3) cycle lengths that varied by 19 or more days (n = 106); (4)
      cycle lengths too variable to report a usual length (n = 29); (5) cycles less
      regular than they had been at age 40 (n = 107); and (6) change in the duration or
      heaviness of menstrual flow compared with age 40 (n = 255). In addition, we
      evaluated hot flashes or night sweats during the previous week (n = 50) and age
      50 or more years (n = 60) as predictors. RESULTS: Definitions 1 to 5 predicted
      time to menopause; definition 6 did not. Definition 1 had the highest positive
      predictive value for ascertained menopause within 2 years and within 4 years;
      definitions 2 and 4 had low to moderate positive predictive values for
      ascertained menopause within 2 years but good positive predictive values for
      ascertained menopause within 4 years. For ascertained menopause within 2 years,
      definition 2 showed the best balance of sensitivity (94%) and specificity (91%).
      CONCLUSION: Simple questions about menstrual variability elicit information that
      is informative about proximity to menopause.

PMID- 14716182
TI  - Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal
      women.
AB  - OBJECTIVE: To assess the efficacy and safety of intravaginal estriol
      administration on urinary incontinence, urogenital atrophy, and recurrent urinary
      tract infections in postmenopausal women. DESIGN: Eighty-eight postmenopausal
      women with urogenital aging symptoms were enrolled in this prospective,
      randomized, placebo-controlled study. Participants were randomly divided into two
      groups, with each group consisting of 44 women. Women in the treatment group
      received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and
      then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women
      in the control group received inert placebo vaginal suppositories in a similar
      regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic
      findings, urethral cytologic findings, urethral pressure profiles, and
      urethrocystometry before as well as after 6 months of treatment. RESULTS: After
      therapy, the symptoms and signs of urogenital atrophy significantly improved in
      the treatment group in comparison with the control group. Thirty (68%) of the
      treated participants, and only seven (16%) of the control participants registered
      a subjective improvement of their incontinence. In the treated participants, we
      observed significant improvements of colposcopic findings, and there were
      statistically significant increases in mean maximum urethral pressure, in mean
      urethral closure pressure as well as in the abdominal pressure transmission ratio
      to the proximal urethra. Urethrocystometry showed positive but not statistically
      significant modifications. CONCLUSIONS: Our results show that intravaginal
      administration of estriol may represent a satisfactory therapeutic choice for
      those postmenopausal women with urogenital tract disturbances who have
      contraindications or refuse to undergo standard hormone therapy.

PMID- 14716183
TI  - Patients' and clinicians' attitudes after the Women's Health Initiative study.
AB  - OBJECTIVE: To assess the effect of the publication of the Women's Health
      Initiative (WHI) study on patients' and physicians' attitudes in relation to
      hormone therapy (HT). DESIGN: A survey focused on the degree of knowledge and on
      the reactions to the WHI study was administered to 600 women allocated in two
      groups according to their socioeconomic status, high (HSES) or low (LSES).
      Additionally, 283 physicians were surveyed to determine their attitudes regarding
      HT after the publication of the WHI study. The rates of HT prescription before
      and after publication of the study were compared. RESULTS: Among patients, HT use
      and knowledge of the WHI study were less common among women of lower
      socioeconomic status (LSES 16.7% v HSES 47.3%, and LSES 15.7% v HSES 67.3%; P <
      0.0001). Of the women in the LSES group who were HT users and had knowledge on
      the subject of the WHI study (n = 30), 56.7% contacted their physicians and 6.6%
      abandoned HT. These rates were similar for women in the HSES group. Among
      physicians, 97.2% of physicians referred to being aware of the WHI study, and
      64.7% modified their clinical approach. The main changes were that 21.5% applied
      more rigorous risk/benefit assessment, 20.1% lowered hormone dosage, 18.8%
      decreased continuous-combined therapy use, 12.1% shortened the duration of HT,
      7.7% abandoned medroxyprogesterone or conjugated estrogen use, and 5.0% increased
      the use of transdermal estrogens, tibolone, or other alternatives. As for
      prescriptions, after the publication of the WHI study, there was an 8.6% drop in
      the rate of HT prescriptions. This decrease was more pronounced for prescriptions
      based on conjugated equine estrogen and medroxyprogesterone acetate. In contrast,
      prescription of transdermal estrogens and tibolone increased 5.2% and 16%,
      respectively. CONCLUSIONS: There was a significant change in physicians' and
      patients' attitudes toward HT after publication of the WHI study.

PMID- 14716184
TI  - The effect of hormone therapy on the risk for age-related maculopathy in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of postmenopausal hormone therapy (HT) as well
      as the use of oral contraceptives and lifetime endogenous hormone exposure on the
      risk for age-related maculopathy (ARM) in postmenopausal women. DESIGN: This was
      a cross-sectional, controlled study. A total of 102 women from 60 to 80 years of
      age who were receiving HT and 100 controls underwent a detailed clinical
      funduscopic evaluation and stereoscopic fundus photography for the presence and
      grading of ARM. All participants completed a standardized questionnaire regarding
      vascular risk factors, HT, and lifetime exogenous and endogenous estrogen and
      progesterone exposure. Statistical analysis was performed using Student's t test,
      chi2 test, and a multivariate logistic regression model. RESULTS: The HT and the
      non-HT groups did not differ in terms of early (11% v 15%), late (6% v 6%), or
      wet (2% v 2%) ARM prevalence rates. Women with ARM were significantly older than
      controls (69 v 66 years; P = 0.001, 95% CI = 0.008 - 0.027) and were more likely
      to have ischemic heart disease (21% v 9%; OR = 2.86, P = 0.03, 95% CI = 0.020 -
      0.360). Lifetime exogenous and endogenous hormone exposures and other
      cardiovascular risk factors were not significantly different among women with ARM
      as compared with controls. CONCLUSION: Postmenopausal HT may not affect the risk
      for either early or late ARM in women aged 60 to 80 years. The risk for both
      entities is not necessarily affected by either exogenous or endogenous lifetime
      hormone exposure. A history of ischemic heart disease may be associated with an
      increased risk for ARM.

PMID- 14716185
TI  - Hormone therapy and ophthalmic artery blood flow changes in women with primary
      open-angle glaucoma.
AB  - OBJECTIVE: To compare the effects of hormone therapy (HT) on plasma viscosity and
      Doppler flow parameters in normal, healthy, postmenopausal women and in women
      with normal-tension and chronic, open-angle glaucoma. DESIGN: Eight
      postmenopausal women with glaucoma (group I) and 15 controls (group II) were
      given HT. The duration of the study was 6 months, and the women were examined in
      basal condition and at the end of the treatment. All women underwent
      ultrasonographic evaluation of pelvic organs and color Doppler analysis of
      uterine, internal carotid, and ophthalmic arteries. Also, plasma viscosity was
      assayed. RESULTS: The ultrasonographic analysis showed that none of the women
      presented with irregular endometrial echoes, polyps, or intracavitary fluid. In
      addition, endometrial thickness never exceeded the normal range (5 mm). Plasma
      viscosity and Doppler parameters significantly improved during therapy. However,
      the ophthalmic artery mean improvements of pulsatility index (-43% v -28%; P =
      0.001), peak systolic blood flow velocity (+35% v +24%; P = 0.026), and time
      averaged maximum velocity (+44% v +32%; P = 0.031) were significantly more
      evident in the control group than in the glaucoma group. CONCLUSIONS: Although,
      in people with glaucoma, vasospasm can increase the risk of visual loss by
      inducing a retrobulbar blood flow reduction, HT seems to beneficially affect the
      ocular vascularization.

PMID- 14716186
TI  - Impairment of sexual activity in middle-aged women in Chile.
AB  - OBJECTIVE: It has been suggested that approximately 40% of women between 40 and
      64 years of age cease their sexual activity. Our objective was to examine the
      reasons that sexual activity has stopped and to determine the effect that this
      behavior has on the marital stability of those middle-aged women. DESIGN: A total
      of 534 healthy women between 40 and 64 years of age who were attending the
      Southern Metropolitan Health Service in Santiago, Chile, were asked to take part
      in the study. RESULTS: The main reasons for sexual inactivity in middle-aged
      women were sexual dysfunction (49.2%), unpleasant personal relationship with a
      partner (17.9%), and lack of a partner (17.7%). These reasons vary with aging; in
      women younger than 45 years, the most frequent reason was erectile dysfunction
      (40.7%); in those between 45 and 59, low sexual desire (40.5%); and, in women
      older than 60 years, the lack of a partner (32.4%). Sexual inactivity did not
      affect marital stability because women without sexual relationships (68.2% of the
      entire sample) were married. Among the divorced women, female sexual dysfunction
      was responsible for only 11.7% of the separations. CONCLUSION: Low sexual desire
      is the main reason for ceasing sexual activity. Nevertheless, stopping sexual
      relationships does not seem to be important in marital stability.

PMID- 14716187
TI  - Effect of tibolone and its metabolites on vascular endothelial growth factor
      isoforms 121 and 165 and thrombospondin-1 mRNA 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 incubation with
      tibolone and tibolone metabolites 3alpha-hydroxytibolone, 3beta-hydroxytibolone,
      Delta4-tibolone, and 17beta-estradiol (E2) in cultured Ishikawa cells. DESIGN:
      Ishikawa cells (immortalized from a well-differentiated human adenocarcinoma cell
      line) were cultured in vitro to confluence. Tibolone, 3alpha-hydroxytibolone,
      3beta-hydroxytibolone, Delta4-tibolone and E2 at concentrations of 1.0, 0.1 and
      0.01 micromol/L were added to confluent cells and further cultured for an
      additional 24 h. Control cells were treated with medium in absence of hormone.
      Total RNA was extracted from control and treated Ishikawa cells. After reverse
      transcription, VEGF, TSP-1 and the housekeeping gene, beta-actin cDNAs, were
      amplified in a polymerase chain reaction spiked with 33p-dCTP. Relative abundance
      of VEGF 121 and 165 isoforms and TSP-1 mRNA was measured by scintillation
      spectroscopy. RESULTS: E2, tibolone, 3alpha-hydroxytibolone, and 3beta
      hydroxytibolone increased both VEGF 121 and 165 mRNA compared with the control.
      However, Delta4-tibolone had no effect on either VEGF 121 or 165 mRNA compared
      with the control. Delta4-Tibolone increased TSP-1 mRNA expression compared with
      control levels. E2, tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone
      did not increase TSP-1 mRNA expression at any concentration. CONCLUSIONS:
      Tibolone and the 3alpha- and 3beta-tibolone metabolites with E2 increased VEGF
      121 and 165 isoforms. Conversely, Delta4-tibolone, which is reported to have
      progestational-like activity, did not stimulate VEGF 121 and VEGF 165 but
      increased TSP-1 mRNA synthesis in cultured Ishikawa cells. We hypothesize, based
      on these data, that the clinical finding of no endometrial growth in women using
      tibolone may be partly related to alterations in these angiogenic factors.

PMID- 14716188
TI  - Hormone therapy prescription among physicians in France and Quebec.
AB  - OBJECTIVE: Our objective was to compare physician characteristics associated with
      high-frequency hormone therapy (HT) prescription between gynecologists and
      general practitioners (GPs) within and between France and Quebec, Canada. DESIGN:
      A self-administered mail survey was sent to a representative sample of 2,000
      physicians in France and 1,000 physicians in Quebec. High-frequency prescribers
      were those who reported prescribing HT to more than 70% of their postmenopausal
      patients. The following characteristics were included in the analysis: country,
      specialty, age, gender, characteristics of the practice (solo or group, private
      or public, rural or urban, number of patients seen daily, duration of practice,
      percentage of women 45 years or older), teaching or research activities,
      participation in education course on HT, and practice patterns relating to
      menopausal women (having patient education materials available, providing
      materials to patients, and discussing the possibility of HT). RESULTS: The
      analysis covered 974 physicians in France (389 GPs and 585 gynecologists) and 452
      physicians in Quebec, Canada (318 GPs and 134 gynecologists). Despite differences
      in health care, in both countries gynecologists were more likely to be high
      frequency prescribers than were GPs, although this difference was smaller in
      Quebec. Canadian physicians were more likely to prescribe HT. The difference
      between countries was greatest among GPs. Except for nationality and practice
      patterns designed to provide women with information, none of the physician
      characteristics was associated with high-frequency prescription among GPs. Among
      gynecologists, only the number of patients per day and the provision of
      information were associated with high-frequency prescription. CONCLUSIONS:
      Notwithstanding a common language, differences in the prescription pattern of HT
      between countries were greatest at the level of primary care than secondary care.
      In both countries, specialists were more likely to prescribe HT than were GPs.
      Implementation of clinical practice guidelines to set baseline standards in the
      field of menopausal health remains a challenge but will need to take into account
      cultural characteristics as well as level of medical care.

PMID- 14716190
TI  - An update on the antiestrogenic effect of smoking: a literature review with
      implications for researchers and practitioners.
AB  - OBJECTIVE: To draw attention to the implications of smoking in the pathogenesis
      of osteoporosis and for the effectiveness and safety of hormone therapy. DESIGN
      Summary of own research and a MEDLINE search of English-language literature on
      the antiestrogenic effect of smoking in pre- and postmenopausal women published
      during the past two decades. RESULTS: Numerous observations suggest that part of
      the detrimental effect of smoking on bone metabolism is mediated by an adverse
      influence on sex-steroid metabolism, and in particular by an estrogen-lowering
      effect. Furthermore, in smokers, serum concentrations of estradiol and estrone
      during oral, but not parenteral, hormone therapy (HT) reach only half the
      concentrations of nonsmokers. Thus, cigarette smoking may reduce the favorable
      effects of HT significantly and may even negate the protective effects. In such
      cases, the failure of preventive therapy is a failure of dosing rather than of HT
      per se. CONCLUSIONS: We urge colleagues to take the antiestrogenic effect of
      smoking into account when drawing conclusions from population-based trials, as
      well as when prescribing HT to their patients for the prevention of menopause
      related health problems.

PMID- 14716189
TI  - Homocysteine impairs estrogen-induced vasodilation in isolated rat arterioles.
AB  - OBJECTIVE: Clinical and basic studies have provided evidence that the
      cardiovascular protective effects of estrogens are partly due to effects on
      vasoreactivity and changes in homocysteine metabolism. Moreover, homocysteine has
      also been shown to influence vasoreactivity. We investigated the influence of
      homocysteine on the rapid vasodilatory effects of estradiol in an isolated vessel
      setup. DESIGN: Isolated, spontaneously constricted, gracilis muscle arterioles
      (diameter approximately 50 micromol/L) from female Wistar rats were cumulatively
      exposed to 10-10 to 10-4 mol/L 17beta-estradiol in the presence of 50 micromol/L
      homocysteine or N-nitro-L-arginine (L-NA) (a blocker of nitric oxide synthesis),
      or both. Control experiments were done without L-NA or homocysteine (n = 6 for
      each series). RESULTS: The dose-dependent dilation during short-term exposure to
      17beta-estradiol was significantly less or absent in arterioles where L-NA,
      homocysteine, or both were present. The addition of 50 micromol/L homocysteine
      significantly increased the spontaneous constriction by 6% to 10%. CONCLUSIONS:
      We showed that a pathophysiological concentration of homocysteine increases the
      spontaneous arteriolar constriction and inhibits the 17beta-estradiol-induced,
      endothelium-mediated, rapid vasodilatory effect on muscle arterioles from the
      female rat. The endothelium-independent vasodilation remained unchanged.

PMID- 14716191
TI  - Raloxifene reduces procarboxypeptidase U, an antifibrinolytic marker. A 2-year
      randomized, placebo-controlled study in healthy early postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to compare the long-term effects of two
      dosages of raloxifene with oral hormone therapy (HT; conjugated equine estrogens
      combined with medroxyprogesterone acetate) on procarboxypeptidase U. DESIGN: In a
      randomized, double-blind, placebo-controlled, 2-year study, 95 healthy,
      nonhysterectomized, early postmenopausal women received either daily raloxifene
      60 mg (n = 24), raloxifene 150 mg (n = 23), HT (conjugated equine estrogens 0.625
      mg + medroxyprogesterone acetate 2.5 mg, n = 24), or placebo (n = 24). At
      baseline and after 6, 12, and 24 months, fasting plasma procarboxypeptidase U
      concentrations were measured. RESULTS: Six months of treatment with raloxifene 60
      mg and raloxifene 150 mg were associated with significant decreases in plasma
      procarboxypeptidase U concentrations, which were sustained after 12 and 24
      months. Raloxifene 60 mg: t = 0, 619 +/- 89 U/L (mean +/- SD); t = 6, 574 +/- 87
      U/L; t = 12, 571 +/- 96 U/L; t = 24, 568 +/- 92 U/L; ANCOVA versus placebo, P =
      0.026. Raloxifene 150 mg: t = 0, 608 +/- 67 U/L; t = 6, 580 +/- 73 U/L; t = 12,
      578 +/- 70 U/L; t = 24, 562 +/- 61 U/L; ANCOVA versus placebo, P = 0.039. No
      significant changes were found in the HT group. CONCLUSION: Long-term treatment
      with raloxifene reduced procarboxypeptidase U plasma concentrations.

PMID- 14716192
TI  - Impact of preventive osteoporosis education on patient behavior: immediate and 3
      month follow-up.
AB  - OBJECTIVE: To evaluate the effectiveness of an educational video on osteoporosis
      at increasing knowledge and preventive health behaviors. DESIGN: A total of 195
      women between 35 and 80 years of age without documented osteopenia or
      osteoporosis, who presented for a gynecological examination in an outpatient
      setting, were enrolled. Of this number, 98 women were randomly assigned to the
      intervention group that viewed the video before their office visit, and 97 women
      were assigned to a control group and saw their physician in a routine manner.
      After their visit, all participants answered a questionnaire that assessed their
      knowledge of osteoporosis and baseline health-related behaviors. Three months
      later, a follow-up questionnaire was mailed to participants, eliciting whether
      preventive behavior had commenced. Frequencies were compared using the Fisher
      exact test (2-tailed). Continuous variables were analyzed using the Student's t
      test. RESULTS: The two groups had no statistically significant differences in
      demographics. The intervention group scored a mean of 92% compared with a mean of
      80% in the control group on the initial osteoporosis assessment questionnaire (P
      < 0.001). The 3-month follow-up questionnaire demonstrated that significantly
      more women in the intervention group started taking calcium supplements (26.5% v
      4.9%; P < 0.001), started taking vitamin D supplements (20.6% v 6.6%; P = 0.02),
      started a program of weight-bearing exercise (13.3% v 1.7%; P = 0.03), and
      started hormone therapy (8% v 1%; P = 0.04). CONCLUSION: The use of an
      educational video on osteoporosis seems to improve patient knowledge and may
      positively impact health-related behaviors.

PMID- 14716193
TI  - The impact of hormones on menopausal sexuality: a literature review.
AB  - Menopause is associated with physiological and psychological changes that
      influence sexuality. During menopause, the primary biological change is a
      decrease in circulating estrogen levels. Estrogen deficiency initially accounts
      for altered bleeding and diminished vaginal lubrication. Continual estrogen loss
      often leads to numerous signs and symptoms, including changes in the vascular and
      urogenital systems. Alterations in mood, sleep, and cognitive functioning are
      common as well. These changes may contribute to lower self-esteem, poorer self
      image, and diminished sexual responsiveness and sexual desire. Other important
      nonhormonal factors that affect sexuality are health status and current
      medications, changes in or dissatisfaction with the partner relationship, social
      status, and cultural attitudes toward older women. The problems in sexual
      functioning related to estrogen deficiency can be treated with hormone therapy
      that includes estrogens alone and estrogens combined with androgens. Vaginal
      lubricants and moisturizers also may be useful in ameliorating postmenopausal
      sexual complaints. This article reviews the literature on the impact of
      menopausal estrogen loss on sexuality and on the effect of hormone therapy on
      sexual function during menopause.

PMID- 14716194
TI  - Electrocardiography.

PMID- 14716195
TI  - Arterial and central venous pressure monitoring.

PMID- 14716196
TI  - Hemodynamic assessment of the critically ill patient.

PMID- 14716197
TI  - Transesophageal echocardiographic monitoring of hemodynamics.

PMID- 14716198
TI  - Transesophageal echocardiography and evaluation of valvular heart disease.

PMID- 14716199
TI  - Respiratory monitoring.

PMID- 14716201
TI  - Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat
      heart.
AB  - Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has
      been reported to have beneficial effects on cardiac function. The authors used
      the Langendorff model of ischemia/reperfusion (I/R) injury in isolated rat heart
      to determine whether ghrelin exerts direct cardioprotective effects. Also, the
      capacity of ghrelin to bind to sarcolemmal membrane fractions before and after
      ischemia and reperfusion was examined. Compared with vehicle administration,
      administration of ghrelin (100-10,000 pM) during the reperfusion period resulted
      in improvement in coronary flow, heart rate, left ventricular systolic pressure,
      and left ventricular end-diastolic pressure. Ghrelin also enhanced the rates of
      left ventricular contraction and relaxation after ischemia following reperfusion.
      Administration of ghrelin during reperfusion reduced myocardial release of
      lactate dehydrogenase and myoglobin, indicating protection against cardiomyocyte
      injury. In addition, ghrelin attenuated the depletion of myocardial ATP resulting
      from ischemia and reperfusion. A receptor-binding assay demonstrated that maximum
      binding capacity of ghrelin to sarcolemmal membranes was significantly increased
      after ischemia and was further increased after I/R. However, Scatchard analysis
      showed that the affinity of ghrelin for its receptor was not altered. The authors
      have concluded that administration of ghrelin during reperfusion protects against
      myocardial I/R injury. The cardioprotective effects are independent of growth
      hormone release and likely involve binding to cardiovascular receptors, a process
      that is upregulated during I/R.

PMID- 14716202
TI  - Adenovirus gene transfer of recombinant endothelial nitric oxide synthase
      enhances contractile function in ventricular myocytes.
AB  - eNOS is expressed in cardiac myocytes and plays an important role in cardiac
      contractile function. This study was designed to determine whether ex vivo eNOS
      gene transfer in ventricular myocytes affects cardiac contractile function.
      Replication-incompetent adenoviral vectors encoding eNOS or marker gene beta
      galactosidase (LacZ) were transduced into adult rat ventricular myocytes at an
      MOI of 10, 50, or 100 for 36 hours. Mechanical and intracellular Ca2+ properties
      of myocytes were evaluated by video-based edge detection and fura-2 fluorescence.
      NOS protein expression and activity were assessed by Western blot and 3H-arginine
      to 3H-citrulline assay. Myocytes transduced with eNOS but not LacZ displayed
      enhanced eNOS but not iNOS expression associated with elevated NOS activity.
      Myocytes transduced with eNOS exhibited significantly elevated peak shortening
      and velocity of shortening/relengthening associated with enhanced basal as well
      as electrically stimulated rise of intracellular Ca2+ compared with control or
      LacZ groups. The durations of shortening and relengthening were comparable in all
      groups. The eNOS-induced mechanical effects were paralleled with elevated
      phosphorylation of Akt. Furthermore, the phosphatidylinositol-3 (PI-3) kinase
      inhibitors wortmannin and LY294002 prevented eNOS-induced mechanical effects.
      These results revealed that gene transfer of eNOS directly promotes cardiomyocyte
      contractile function and intracellular Ca2+ handling, suggesting therapeutic
      potential of eNOS gene transfer.

PMID- 14716203
TI  - Bepridil block of recombinant human cardiac IKs current shows a time-dependent
      unblock.
AB  - Whole-cell patch-clamp techniques were employed to examine the effects of
      bepridil, a Ca2+ channel blocker with Vaughan Williams class III action, on a
      slow component of cardiac delayed rectifier K+ current (IKs), which was
      reconstituted in HEK293 cells by transfecting KCNQ1 and KCNE1. Micromolar
      bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a
      concentration-dependent manner (IC50 = 5.3 +/- 0.7 microM at -40 mV from 1000
      milliseconds test pulse). When the effect of the drug was examined with a short
      test pulse protocol (250 milliseconds), IC50 became two-fold smaller than that
      measured with 1000 milliseconds test pulse (2.5 +/- 0.8 microM). The envelope-of
      tails protocol was used to assess how the duration of depolarizing pulse affects
      the drug action on the outward KCNQ1/KCNE1 channel current. The drug
      significantly inhibited tail currents more potently during shorter pulses (<600
      milliseconds). Bepridil's block was therefore time dependent, and its binding
      affinity to the channel was greater in the closed state channel, as evidenced by
      unblocking during prolonged depolarization. These properties of channel blockade
      appear to underscore the mechanism of bepridil's effect on IKs current.

PMID- 14716204
TI  - Chronic treatment with fluvastatin improves smooth muscle dilatory function in
      genetically determined hyperlipoproteinemia.
AB  - We hypothesized that the HMG-CoA reductase inhibitor fluvastatin, does not only
      improve endothelium-dependent vasorelaxation, but that it also increases vascular
      smooth muscle reactivity in hyperlipoproteinemia. New Zealand White (NZW) rabbits
      aged 37 weeks (control), Watanabe Heritable Hyperlipidemic rabbits (WHHL) aged 37
      weeks, and WHHL aged 35 weeks with fluvastatin treatment of 17 weeks (10 mg/kg/d)
      were examined. Aortas were isolated for isometric tension recording. Both
      endothelium-dependent and independent relaxation were impaired in WHHL.
      Fluvastatin significantly restored impaired endothelium-independent relaxation
      (WHHL: 57 +/- 12 versus WHHL+ fluvastatin: 150 +/- 22%; P < 0.05) and in tendency
      endothelium-dependent relaxation (WHHL: 26 +/- 5 versus WHHL+ fluvastatin: 83 +/-
      29%; (P = 0.07)). In parallel, fluvastatin restored nitrite plasma level in
      hyperlipoproteinemic animals (WHHL: 480 (13-3821) versus WHHL+ fluvastatin: 808
      (467-1595) nmol; P < 0.05). Thus, chronic treatment with fluvastatin not only
      improves endothelial but also vascular smooth muscle function in
      hyperlipoproteinemia, which may contribute to the beneficial clinical effects of
      statins.

PMID- 14716205
TI  - Lesion progression in apoE-deficient mice: implication of chemokines and effect
      of the AT1 angiotensin II receptor antagonist irbesartan.
AB  - We recently described that a treatment with the angiotensin AT1 receptor
      antagonist irbesartan inhibits atherosclerotic lesion development, macrophage
      accumulation, and monocyte chemoattractant protein-1 (MCP-1) as well as the
      chemokine KC expression in apolipoprotein E-deficient (apoE-deficient) mice. The
      present study addresses whether these and other chemokines are expressed not only
      during the initiation but also during the development of atherosclerotic lesions
      and whether irbesartan can inhibit the expression of these chemokines during
      lesion progression. The time course of lesion development was assessed in apoE
      deficient mice aged 1 to 9 months and the relative expression of chemokines was
      quantified by RT-PCR. Significant lesion formation already appeared in 3-month
      old apoE-deficient mice, and progressed further to the age of 9 months. The
      expression of MCP-1 and KC (the mouse homologue of Groalpha), was induced at 1
      month in apoE-deficient as compared with wild type (C57/Bl6) mice, and was
      observed before any detectable histologic changes. MCP-1 and KC expression
      remained high during lesion progression. The expression of macrophage
      inflammatory protein-2 (MIP-2, the mouse Grobeta/gamma homologue) and macrophage
      inflammatory protein-1alpha (MIP-1alpha) was increased in lesions from 4-month
      old mice onward, whereas Regulated upon Activation of Normal T-cells Expressed
      and Secreted (RANTES) was significantly induced in 6- to 9-month-old mice only.
      Irbesartan (50 mg/kg/d) administered from the age of 3 months onward
      significantly reduced the progression of the lesions as well as the expression of
      the chemokines. A short-term treatment with irbesartan significantly inhibited
      the expression of MCP-1 and KC, suggesting that activation of the renin
      angiotensin system is involved in up-regulation of these chemokines and that this
      effect represents a potential mechanism by which irbesartan inhibits plaque
      development and progression.

PMID- 14716206
TI  - Inhibitory effect of epigallocatechin 3-O-gallate on vascular smooth muscle cell
      hypertrophy induced by angiotensin II.
AB  - Recent evidence indicates that epigallocatechin 3-O-gallate (EGCG), the major
      catechin derived from green tea leaves, lowers the risk of cardiovascular
      diseases such as atherosclerosis and hypertension. However, a precise mechanism
      for this biologic function has not yet been clearly delineated. Angiotensin II
      (Ang II) stimulates vascular smooth muscle cell (VSMC) hypertrophy, which is a
      critical event in the development of atherosclerosis, hypertension, and
      angioplasty-induced restenosis. In the present study, we show that EGCG inhibits
      Ang II-stimulated VSMC hypertrophy, as determined by [3H]leucine incorporation
      into VSMC. Since mitogen-activated protein kinase (MAPK) families are involved in
      cell growth, we determined whether EGCG affects them. EGCG pretreatment did not
      exert any significant changes in Ang II-stimulated activation of extracellular
      signal-regulated kinase (ERK) and p38 MAPK. EGCG only inhibited Ang II-stimulated
      activation of c-Jun N-terminal kinase (JNK). Moreover, EGCG suppressed Ang II
      induced c-jun mRNA expression. In contrast, EGC, a structural analogue of EGCG,
      did not inhibit the JNK activity or c-jun mRNA expression. In addition, a
      specific JNK inhibitor, SP600125, dose-dependently suppressed Ang II-stimulated
      VSMC hypertrophy. These results suggest that the effect of EGCG on Ang II-induced
      VSMC hypertrophy is due to specific inhibition of the JNK signaling pathway at
      both transcriptional and posttranslational levels, which may underlie its
      beneficial effect on the cardiovascular diseases.

PMID- 14716208
TI  - Myocardial protection with the non-selective endothelin receptor antagonist L
      753,037 following acute coronary artery occlusion in the dog.
AB  - SUMMARY: Efficacy of a new, potent non-selective endothelin antagonist, l-753037,
      was examined in a model of canine coronary artery occlusion and reperfusion to
      assess whether blockade of both ETA and ETB receptors would enhance or reduce
      myocardial ischemic injury. Instrumented dogs were randomized to receive vehicle
      (n = 9) or l-753037 (0.1 microg/kg/min, n = 9) by intracoronary infusion 30
      minutes before a 90-minute LCx coronary artery occlusion and through 4 hours of
      reperfusion. After 4 hours of reperfusion, plasma ET-1 levels rose significantly
      in both groups: 24 +/- 3 fmol/ml in vehicle animals (P < 0.01) versus 42 +/- 5
      fmol/ml with l-753037 (P < 0.05). Treatment with l-753037 normalized total LCx
      flow and regional myocardial flow after 4 hours of reperfusion in all regions.
      LCx flow was reduced 16% from pre-occlusion baseline (P = 0.45) with treatment
      compared with 35% with vehicle (P < 0.01). Endocardial flow in the risk region
      returned to baseline values with l-753037 treatment but was reduced approximately
      50% in vehicle animals. l-753037 treatment was associated with a 38% reduction in
      infarct size (24.1 +/- 3.9% AAR with l-753037 treatment versus 38.7 +/- 3.1% with
      vehicle, P < 0.01). Thus, a non-selective endothelin antagonist provides
      significant myocardial protection primarily by improving regional myocardial flow
      distribution following reperfusion and demonstrated no detrimental effects
      associated with blockade of the ETB receptor.

PMID- 14716207
TI  - Disruption of the actin cytoskeleton up-regulates iNOS expression in vascular
      smooth muscle cells.
AB  - Cytokines and bacterial lipopolysaccharide (LPS) induce the expression of
      inducible nitric oxide synthase (iNOS), resulting in the release of nitric oxide
      (NO) from vascular smooth muscle cells. We here demonstrated that disruption of F
      actin formation by sequestration of G-actin with the toxin latrunculin B (Lat B)
      dramatically potentiated LPS-induced iNOS mRNA and protein expression. We also
      showed that Lat B enhanced interleukin-1beta- andbgr;- and TNFalpha-induced NO
      production. Lat B by itself had little or no effect on iNOS expression.
      Cytochalasin D also enhanced LPS-induced NO production. Lat B dose-dependently
      enhanced LPS-induced iNOS promoter activity but had no effect on the stability of
      iNOS mRNA. Staining of F-actin with nitrobenzoxadiazole (NBD)-phallacidin
      demonstrated that Lat B significantly impaired F-actin stress fiber formation.
      These data indicate that disruption of the actin cytoskeleton up-regulates
      cytokine-induced iNOS expression via transcriptional regulation. Further analysis
      of the signaling pathway from the actin cytoskeleton to iNOS expression may yield
      new insight into the mechanism of iNOS regulation.

PMID- 14716209
TI  - Endothelial and smooth muscle cell dysfunction in human atherosclerotic radial
      artery: implications for coronary artery bypass grafting.
AB  - The radial artery (RA) is increasingly used as coronary artery bypass graft. In
      rare cases, however, it is macroscopically atherosclerotic at time of harvest. We
      examined how the regulation of vascular tone is altered under such circumstances.
      Macroscopically evident atherosclerotic lesions were observed in 3 of 429 RA
      (0.7%) isolated within 2 years. Histology revealed severe plaque formation;
      however, von Willebrand Factor staining showed a morphologically intact
      endothelium (n = 3). Endothelium-dependent relaxations to acetylcholine (10(-5)
      M) were reduced in atherosclerotic RA (32 +/- 6%; n = 3) as compared with control
      (78 +/- 4%; n = 10; P = 0.0001). Receptor-independent contractions to KCl (100
      mM) were reduced in atherosclerotic RA (33.19 +/- 5.06 mN; n = 3) as compared
      with control (108.02 +/- 15.76 mN; n = 9; P < 0.05). Similarly, contractions to
      thrombin (1 U/ml) were reduced in atherosclerotic RA (3.02 +/- 1.58 mN; n = 3) as
      compared with control (10.97 +/- 5.12 mN; n = 8). Likewise, receptor-mediated
      contractions to norepinephrine were reduced in atherosclerotic RA (27.64 +/-
      12.48 mN; n = 3) as compared with control (82.74 +/- 11.36 mN; n = 9; P < 0.05).
      Atherosclerosis is rare in RA of patients with coronary artery disease, but it
      does occur. Atherosclerotic RA exhibits a dysfunction of both endothelium and
      vascular smooth muscle. This dysfunction may favor thrombus formation and
      accelerated atherogenesis. Therefore, atherosclerotic RA should not be used for
      coronary artery bypass grafting.

PMID- 14716210
TI  - The role of endothelin in mediating ischemia/hypoxia-induced atrial natriuretic
      peptide release.
AB  - The aim of the present study was to investigate the putative role of endothelin
      (ET) in mediating ischemia/hypoxia-induced ANP release utilizing exogenous ET-1
      or ET receptor antagonists (BQ-123 or Bosentan). Isolated rat hearts with non
      distended atria were perfused using a Langendorff apparatus and heart rate
      maintained constant via atrial pacing. Global ischemia was induced either by
      direct reduction in perfusion or by infusion of exogenous ET-1 (5 x 10(-10) M)
      for 30 minutes. Perfusion with the ET receptor antagonists, BQ-123 (10(-6) M) or
      Bosentan (10(-5) M) was initiated 10 minutes before onset of ischemia. Moderate
      or severe ischemia was induced by reduction (52-61% and 70-82%, respectively) in
      perfusate flow. Thirty minutes of ischemia/hypoxia (5% O2) was followed by 30
      minutes of reperfusion/re-oxygenation. Both moderate and severe ischemia
      increased ANP release. BQ-123 and Bosentan did not affect basal or ischemia
      induced ANP release. Exogenous ET-1 perfusion induced a late increase in ANP
      release (P < 0.01) that did not exceed the increase in ANP release associated
      with equivalent direct flow reduction. Hypoxia induced an 8-fold increase in ANP
      release rate. The ANP release rate returned toward basal levels after re
      oxygenation. Bosentan, but not BQ-123, significantly attenuated (P < 0.01)
      hypoxia-induced ANP release. In conclusion, in this system, ANP release is
      stimulated by moderate (or severe) ischemia and severe hypoxia independent of
      change in atrial distension; endogenous ET does not mediate basal and ischemia
      induced ANP release; and hypoxia-induced ANP release is partially modulated via
      interaction with endogenous ET.

PMID- 14716211
TI  - Changes of central norepinephrine, beta-endorphin, LEU-enkephalin, peripheral
      arginine-vasopressin, and angiotensin II levels in acute and chronic phases of
      sino-aortic denervation in rats.
AB  - We and others have demonstrated that impaired arterial baroreceptor reflex (ABR)
      function is one of the major causes of hypertension-associated end organ damage.
      The goal of this study was to clarify the potential neuro-humoral mechanisms
      responsible for impaired ABR-induced end organ damage. The sino-aortic denervated
      (SAD) rat was used as an animal model of ABR dysfunction. One-week SAD rats were
      characterized by hypertension, tachycardia, increased norepinephrine content, and
      decreased beta-endorphin and leu-enkephalin content in hypothalamus and medulla
      oblongata, and increased plasma levels of arginine-vasopressin. In 18-week SAD
      rats, the 24-hour average arterial pressure, heart rate, beta-endorphin, and leu
      enkephalin content in hypothalamus and medulla oblongata and plasma levels of
      arginine-vasopressin and angiotensin II were not different from those measured in
      ABR-intact rats. However, blood pressure variability and angiotensin II content
      in kidney and left ventricle increased. When exposed to chronic stress,
      exaggerated changes in arterial pressure, blood pressure variability, the levels
      of central norepinephrine, beta-endorphin and leu-enkephalin, plasma arginine
      vasopressin and angiotensin II, and tissue angiotensin II were found in 18-week
      SAD rats. These data indicate that a long-term impairment of ABR leads to chronic
      activation of central noradrenergic neurons and tissue renin-angiotensin system,
      and that stress induces exaggerated responses of neuro-humoral factors and
      hemodynamics in SAD rats. Thus, if the present results hold true for humans, one
      can expect abnormal neurotransmitter/neuromodulator responses to environmental
      insults in patients with impaired ABR function.

PMID- 14716212
TI  - Nitric oxide and prostaglandins modulate pressure-induced myogenic responses of
      intramural coronary arterioles.
AB  - The myogenic response, an active constriction and dilation of vessels to changes
      in intravascular pressure, can play an important role in the regulation of
      coronary blood flow. The characteristics of the myogenic response and its
      modulation by endothelium-derived factors are organ and location specific and
      have not been studied extensively in intramural coronary arterioles. Thus, distal
      intramural branches (approximately 100 and approximately 170 microm active and
      passive diameter, respectively) of the left anterior descending coronary artery
      of rats were isolated and cannulated. Step increases in intraluminal pressure
      from 0 to 40 mm Hg elicited increases in diameter, whereas further increases in
      pressure from 50 to 150 mm Hg resulted in constrictions. In control, the pressure
      induced myogenic tone of coronary arterioles was 67.3 +/- 2.7% of passive
      diameter (PD, obtained in Ca2+-free solution) at 60 mm Hg. Nomega-nitro-L
      arginine (L-NNA, 10(-5) M), an inhibitor of nitric oxide synthase, reduced the
      initial arteriolar diameter (by 44.8 +/- 5.1 microm at 2 mm Hg, P < 0.05) and
      significantly mitigated increases in diameter to lower pressures and
      constrictions to higher pressures (41.1 +/- 5.6% of PD at 60 mm Hg).
      Administration of adenosine restored the initial diameter in the presence of l
      NNA, but the increase in diameter to lower pressures and the decrease in diameter
      to higher pressures observed under control conditions remained greatly inhibited.
      Inhibition of prostaglandin synthesis, or PGH2/TxA2 receptors significantly
      reduced the constrictions to higher pressures as compared with control
      (indomethacin: from 57.9 +/- 4.8% of PD to 67.0 +/- 4.7% of PD at 150 mm Hg).
      Thus, because in isolated intramural coronary arterioles of rats a negative slope
      for the pressure-diameter curve develops only in the presence of nitric oxide and
      constrictor prostaglandins, they seem to be essential for the normal development
      of the myogenic response.

PMID- 14716213
TI  - Cardiovascular effects of eugenol, a phenolic compound present in many plant
      essential oils, in normotensive rats.
AB  - Cardiovascular effects of intravenous (i.v.) treatment with eugenol (Eug), a
      natural pungent present in many plant essential oils, were investigated in
      normotensive rats. In either anesthetized or conscious rats, i.v. bolus
      injections of Eug (1 to 10 mg/kg) elicited immediate and dose-dependent
      hypotension and bradycardia. Magnitude of Eug-induced hypotension was similar in
      both groups. Pretreatment of anesthetized rats with bilateral vagotomy almost
      abolished the bradycardic responses to Eug without affecting the hypotension.
      Likewise, i.v. pretreatment of conscious rats with methylatropine (1 mg/kg) or
      hexamethonium (30 mg/kg) significantly reduced the Eug-induced bradycardia
      without affecting the hypotension. However, i.v. pretreatment with the nitric
      oxide synthase inhibitor, NG-nitro-L-arginine methyl (L-NAME, 20 mg/kg), affected
      neither the hypotension nor the bradycardia elicited by Eug. In rat mesenteric
      bed preparations precontracted with potassium (60 mM), Eug (0.1-2 mM) induced a
      reversible and concentration-dependent vasodilator effect, which remained
      unaffected by atropine (1 microM). These results show that i.v. treatment of rats
      with Eug induces dose-dependent hypotension and bradycardia, which occurred
      independently. The bradycardia appears dependent upon the presence of an intact
      and functional parasympathetic nerve drive to the heart while the hypotension is
      due to an active vascular relaxation rather than withdrawal of sympathetic tone.
      Released nitric oxide from vascular endothelial cells seems to be not involved in
      the mediation of Eug-induced hypotension.

PMID- 14716214
TI  - Enalapril interferes with the effect of diclofenac on leucocyte-endothelium
      interaction in hypertensive rats.
AB  - Nonsteroidal anti-inflammatory drugs are known to attenuate the effects of some
      antihypertensive agents. However, the effect these drugs have on leukocyte
      migration when combined with antihypertensive agents has not been studied. To
      investigate this effect, we treated spontaneously hypertensive rats with saline,
      diclofenac, enalapril, or diclofenac combined with enalapril and observed
      leukocyte-endothelium interaction. Blood pressure was increased by diclofenac,
      reduced by enalapril and reduced by the combination of the two. Diclofenac did
      not interfere with the blood pressure-lowering effect of enalapril. Internal
      spermatic fascia venules were observed using intravital microscopy. Diclofenac
      reduced rollers, whereas enalapril, alone or combined with diclofenac, had no
      significant effect on rollers. All treatments reduced adherent and migrated
      leukocytes and expression of endothelial intercellular adhesion molecule-1.
      Venular shear rate, venular diameters, number of circulating leukocytes, and post
      leukotriene B4 expression of l-selectin and CD11/CD18 integrin in leukocytes were
      unaffected by any treatment. Expression of P-selectin was reduced by diclofenac
      and unaffected by enalapril, even when combined with diclofenac. Our data suggest
      that, although diclofenac does not interfere with the enalapril anti-hypertensive
      effect, enalapril interferes with the effect diclofenac has on leukocyte rolling
      and endothelial P-selectin expression. Involvement of reduced endothelial
      intercellular adhesion molecule-1 expression might explain the lower numbers of
      adherent and migrated leukocytes. The anti-inflammatory properties of a
      nonsteroidal anti-inflammatory drug could therefore be attenuated in hypertensive
      patients receiving an angiotensin-converting enzyme inhibitor.

PMID- 14716215
TI  - Effect of sarpogrelate hydrochloride, a 5-HT2 blocker, on insulin resistance in
      Otsuka Long-Evans Tokushima fatty rats (OLETF rats), a type 2 diabetic rat model.
AB  - 5-hydroxytryptamine (5-HT) is closely related to pathogenesis of angiopathy in
      type 2 diabetes. Acute and chronic effects of sarpogrelate hydrochloride
      (sarpogrelate), a 5-HT2 blocker, on glucose tolerance and insulin resistance were
      examined. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2
      diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d
      sarpogrelate treatment of 4 weeks (HTB group) and without (control group). The
      glucose infusion rate was significantly increased in the HTB group compared with
      the control group. The blood glucose levels after oral glucose tolerance test and
      levels of plasma insulin and lipids were significantly lower in the HTB group
      than in the control group. To investigate mechanism of the improvement by
      sarpogrelate, acute effect of 5-HT and its blocking effect by sarpogrelate on
      blood levels of glucose were examined in 25-week-old Sprague-Dawley rats. Blood
      glucose levels were significantly increased by administration of 5-HT. This
      increase was reversed by pretreatment of sarpogrelate. A plasma adrenaline level
      also rose significantly by injection of the 5-HT and was prevented by
      pretreatment of sarpogrelate. These results indicate that sarpogrelate improves
      insulin resistance in type 2 diabetic rats.

PMID- 14716216
TI  - Minimally invasive, in vivo exploration of mouse small artery reactivity.
AB  - The aim of the study was to investigate in vivo arterial reactivity in the mouse
      hind limb using Orthogonal Polarisation Spectral (OPS) imaging, which delivers
      high-contrast images of vascular beds by visualizing red blood cells. After
      minimal skin invasion of anesthetized mice, the OPS probe was placed on the hind
      limb continuously superfused with physiological saline solution. Then, the
      response of the saphenous artery (average luminal diameter 127 +/- 3 microm; n =
      15) to topical application of increasing concentrations of acetylcholine or
      phenylephrine was examined. Mean carotid arterial blood pressure was unaffected
      during the experiment. The basal diameter decreased by 70% during exposure to
      phenylephrine (pD2: 5.65 +/- 0.08; n = 9), while acetylcholine augmented basal
      diameter up to 199% (pD2: 6.55 +/- 0.12; n = 6). Application of sodium
      nitroprusside did not further increase arterial diameter following acetylcholine
      exposure. After washing out, arterial luminal diameters returned to initial
      values. Second exposure to vasoactive agents demonstrated that changes in
      diameter were reproducible with time and not different between left and right
      saphenous arteries. Thus, OPS imaging is an in vivo dye-free, simple and
      minimally invasive approach, which provides unique information regarding the
      behavior of vascular network within conditions of cellular and physiological
      homeostasis.

PMID- 14716217
TI  - The influence of diazepam and midazolam on adenosine-induced forearm vasodilation
      in humans.
AB  - Adenosine is an endogenous purine with vasodilating and cardioprotective
      properties. Animal experiments have shown that some benzodiazepine-induced
      effects can be explained by potentiation of adenosine effects, via inhibition of
      the nucleoside transport system. The objective of this study was to determine
      whether the frequently used benzodiazepines diazepam and midazolam increase
      adenosine-induced vasodilation in the human forearm vascular bed, measured by
      venous occlusion plethysmography. Adenosine (0.6, 6, 20, and 60 nmol/min/dl
      ForeArm Volume) was infused into the brachial artery with and without concomitant
      separate infusion of diazepam (21 nmol/min/dl, n = 9) and midazolam (23
      nmol/min/dl, n = 8). Plasma concentrations of diazepam resp. midazolam at the end
      of the infusion protocol averaged 0.5 +/- 0.2 microg/ml plasma (1.6 microM) for
      diazepam versus 1.2 +/- 0.4 microg/ml plasma (3 microM) for midazolam. Intra
      arterial infusion of the benzodiazepines did not alter baseline vascular tone,
      and had no significant influence on the forearm vasodilator response to
      adenosine. The adenosine-induced relative change in Forearm Vascular Resistance
      (FVR) was -3 +/- 7, -48 +/- 8, -75 +/- 6, and -85 +/- 3% in the absence and 3.5
      +/- 11, -54 +/- 5, -74 +/- 5, and -82 +/- 3% resp. in the presence of diazepam (P
      > 0.1, repeated measures ANOVA, n = 9). Likewise, in the absence resp. presence
      of midazolam, FVR fell by 1 +/- 6, 55 +/- 5, 74 +/- 3, and 84 +/- 2% resp. 11 +/-
      11, 59 +/- 2, 80 +/- 3, and 87 +/- 2% (P > 0.1, n = 7). Intra-brachial infusion
      of diazepam and midazolam resulting in forearm concentrations in the high
      therapeutic range does not augment adenosine-induced forearm vasodilation. A
      possible interaction at supra-therapeutic levels of the benzodiazepines can not
      be excluded from the present study, but lacks clinical significance.

PMID- 14716218
TI  - Protein kinase C masks nitric oxide synthase activity in vascular smooth muscle
      under basal conditions.
AB  - Under basal conditions there is no observable nitric oxide synthase (NOS)
      activity in vascular smooth muscle (VSM). Pretreatment of endothelium-denuded
      aortic rings from Sprague-Dawley rats with 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine (H-7), (0.1 micromol/L) significantly attenuated phenylephrine
      (PE)-induced contractile responses in a dose-dependent manner. In the presence of
      10 micromol/L Nomega-nitro-L-arginine (L-NNA) or 0.1 mmol/L aminoguanidine (AG),
      the inhibition of contractions at 10 nmol/L PE by H-7 was blocked by 88% or 52%,
      respectively. The blockade by antagonists was completely reversed by l-arginine
      but not by d-arginine, and alone they did not significantly alter PE-induced
      contraction of endothelium-denuded aorta. Methylene blue (MB, 50 micromol/L) also
      inhibited the action of H-7. The inhibitory effect of H-7 occurred after 5
      minutes and was reversible. PE-induced contraction was also inhibited by the
      selective protein kinase C inhibitors calphostin C (10 micromol/L), and
      bisindolylmaleimide IV (Bis-IV, 10 micromol/L), but not by the selective protein
      kinase A inhibitor H-89 (0.1 micromol/L). These results indicate protein kinase C
      inhibits NOS activity in VSM under basal conditions. Incubation of tissues with
      either H-7 or calphostin C stimulates NO production, and immunocytochemical
      studies reveal the presence of NOS in VSM under basal conditions.

PMID- 14716219
TI  - Effect of candesartan and verapamil on exercise tolerance in diastolic
      dysfunction.
AB  - Diastolic dysfunction may be exacerbated by increased systolic blood pressure
      (SBP) during exercise. Ang II may contribute to this process. We performed a
      randomized, double-blind, crossover study of two weeks of candesartan (16 mg) and
      verapamil (SR 160 mg). The 21 subjects were 64 +/- 10 years old with ejection
      fraction greater than 50%, no ischemia, mitral flow velocity E/A less than 1,
      normal resting SBP (< 150 mm Hg), and SBP greater than 200 mm Hg during exercise.
      Exercise tolerance was assessed using a Modified Bruce Protocol at baseline and
      after each two-week treatment period, separated by a two-week washout period.
      Quality of life (QOL) was assessed using the Minnesota Living with Heart Failure
      questionnaire. During exercise, Ang II levels increased from 29 +/- 18 to 33 +/-
      18 pg/ml (P < 0.05). SBP during exercise was 213 +/- 9 mm Hg at baseline and
      similarly reduced by candesartan (198 +/- 18, P < 0.01) and verapamil (197 +/-
      14, P < 0.01). With candesartan, exercise time increased from 793 +/- 182 seconds
      to 845 +/- 163 seconds (P < 0.05), and QOL improved from 11 +/- 14 to 5 +/- 6 (P
      < 0.05). In contrast, verapamil did not significantly improve exercise time or
      QOL. In patients with mild diastolic dysfunction at rest and a hypertensive
      response to exercise, both Ang II receptor blockade and verapamil blunted the
      hypertensive response to exercise. Ang II blockade increased exercise tolerance
      and improved QOL.

PMID- 14716220
TI  - Cardioprotective effect of zofenopril in perfused rat heart subjected to ischemia
      and reperfusion.
AB  - We investigated the effect of different ACE inhibitors on tissue injury in
      isolated rat hearts subjected to 30 minutes of ischemia followed by 120 minutes
      of reperfusion. Zofenoprilat (1-100 microM), but not enalaprilat or lisinopril,
      significantly reduced infarct size, as estimated on the basis of
      triphenyltetrazolium chloride staining. The protection was not reproduced by the
      angiotensin II receptor antagonist irbesartan, and it was partly abolished by the
      bradykinin receptor antagonist HOE 140. Zofenoprilat molecule contains a
      sulfhydryl group, and its administration, as compared with enalaprilat or
      lisinopril administration, was associated with better preservation of protein
      thiols at the end of ischemia. We conclude that zofenopril has a specific
      cardioprotective effect, which might be related either to interference with
      bradykinin metabolism or to preservation of protein sulfhydryl groups.

PMID- 14716221
TI  - Effects of the combination of low-dose nifedipine GITS 20 mg and losartan 50 mg
      in patients with mild to moderate hypertension.
AB  - Most hypertensive patients require more than one medication to effectively
      control elevated blood pressure (BP) values. This multicenter, randomized, double
      blind study was aimed at testing the efficacy and safety of the combination of
      low-dose nifedipine GITS 20 mg/ losartan 50 mg compared with either monotherapy
      in patients with grade 1 to 3 hypertension over an eight-week period. Of 352
      patients enrolled in the study, 300 were randomized. All the three treatments
      lowered elevated BP without clinically relevant changes in heart rate. All the
      three treatments lowered mean 24-hour diastolic BP: nifedipine GITS/losartan 
      10.6 mm Hg, losartan -5.4 mm Hg, nifedipine GITS 20 mg -8.0 mm Hg. There was a
      statistically significant difference of diastolic BP change between patients
      receiving losartan compared with those receiving combination treatment (P <
      0.05). Diastolic BP trough-to-peak ratio and smoothness index were highest in the
      patient group receiving combination therapy (70%). Nifedipine GITS monotherapy
      had the highest systolic BP trough-to-peak ratio of all treatment arms (78%) and
      higher diastolic BP trough-to-peak ratio and smoothness index than losartan
      monotherapy. All treatments were safe. These data provide evidence that in
      hypertensive patients combination of nifedipine GITS 20 mg and losartan 50 mg
      improves control of systolic and diastolic BP compared with either monotherapy.

PMID- 14716222
TI  - Moxonidine, an antihypertensive agent, is permissive to alpha1-adrenergic
      receptor pathway in the rat-tail artery.
AB  - To investigate whether alpha1-adrenergic receptors were involved in the
      contractile response of tail arteries to moxonidine, isolated ring segments of
      tail arteries from male adult Sprague-Dawley rats were studied. Moxonidine (EC50
      = 1.3 microM) and the alpha1-agonist phenylephrine (EC50 = 2.5 microM) increased
      tension development in the rat-tail artery similarly. The response to moxonidine
      (1 microM) could be blocked by both alpha1-adrenoceptor blockers prazosin (IC50 =
      1 nM), and urapidil (IC50 = 14 nM), and also by alpha2-adrenoceptor blockers,
      yohimbine (IC50 = 49 nM) and efaroxan (IC50 = 49 nM). Combination drug treatment
      (urapidil and yohimbine, or yohimbine and prazosin) was more effective in
      blocking the contractile response to moxonidine, than treatment with prazosin or
      urapidil alone. Comparison of pA2 values for prazosin in the presence of
      moxonidine (9.35) or phenylephrine (10.2) confirm that alpha1-adrenergic
      receptors are involved in the contractile response of rat-tail artery to
      moxonidine.

PMID- 14716223
TI  - 17-beta estradiol independently regulates erythropoietin synthesis and NOS
      activity during hypoxia.
AB  - We reported previously that 17-beta estradiol (E2-beta) attenuates hypoxic
      induction of erythropoietin (EPO) synthesis in rats. We hypothesized this
      attenuation is mediated by increased nitric oxide (NO) bio-availability. To
      investigate this hypothesis, ovariectomized estrogen-depleted rats were
      instrumented with arterial and venous catheters and treated with either E2-beta
      (20 microg/24 hrs) or vehicle (polypropylene glycol) for 7 days. Rats were placed
      in Plexiglas boxes and administered a bolus of either the NO synthase inhibitor,
      Nomega-nitro-L-arginine (l-NNA, 15 mg/kg) or saline. Following this bolus, saline
      or l-NNA was continuously infused (15 mg/kg/h) throughout the 8 hours of hypoxic
      exposure (12% O2). Hypoxia increased plasma NO metabolites (NOx) in both saline
      groups but more in E2-beta-treated rats. l-NNA prevented this increase in both
      groups. Renal endothelial NO synthase (NOS) expression was unaltered by hypoxia,
      l-NNA, or E2-beta. Despite preventing increases in plasma NOx during hypoxia, l
      NNA did not affect E2-beta attenuation of EPO synthesis. We conclude that E2-beta
      independently attenuates hypoxic induction of EPO and augments hypoxic increases
      in NO synthesis.

PMID- 14716224
TI  - AT1 and AT2-receptor antagonists inhibit Ang II-mediated facilitation of
      noradrenaline release in human atria.
AB  - It is generally accepted that regulation of blood pressure and sympathetic
      neurotransmission by angiotensin (Ang) II is brought about through activation of
      AT1-receptors. Since recent studies demonstrated a high proportion of AT2
      receptors in the human heart, the aim of our study was to investigate whether Ang
      II modulates noradrenaline release also through activation of AT2-receptors in
      this tissue. Human atrial appendages were prelabeled with [3H]-noradrenaline and
      electrically field-stimulated. Stimulation-induced outflow of radioactivity was
      taken as an index of endogenous noradrenaline release. Ang I and II enhanced
      noradrenaline release in a dose-dependent manner up to 55 and 72%, respectively.
      These effects were blocked by the selective AT1-receptor antagonists EXP3174 and
      irbesartan (10 nmol/L). Moreover, the selective AT2-receptor antagonists PD123319
      and CGP42112A (0.1 and 1 micromol/L) also inhibited Ang II-induced facilitation
      of noradrenaline release. Captopril (5 micromol/L) shifted the dose response
      curve for Ang I less potent to the right than EXP3174 (10 nmol/L). Ang I and II
      enhanced the stimulation-induced noradrenaline release significantly more potent
      in tissues of patients pretreated with ACE inhibitors than without. In
      conclusion, both AT1- and AT2-receptors seem to play a role in Ang II-mediated
      facilitation of noradrenaline release in the human heart. Chronic treatment with
      ACE inhibitors appears to affect cardiac sympathetic neurotransmission possibly
      by upregulation of presynaptic Ang II receptors.

PMID- 14716225
TI  - High-resolution computed tomography is useful for early diagnosis of severe acute
      respiratory syndrome-associated coronavirus pneumonia in patients with normal
      chest radiographs.
AB  - OBJECTIVE: We investigated the usefulness of high-resolution computed tomography
      (HRCT) in early detection of severe acute respiratory syndrome (SARS)-associated
      coronavirus pneumonia and analyzed HRCT findings associated with potentially more
      severe disease. METHODS: All patients with suspected SARS and normal chest
      radiographs on admission within the study period were subjected to HRCT
      examination. The clinical, radiologic, and laboratory data of patients who were
      confirmed to have SARS-associated coronavirus infection by a positive
      nasopharyngeal aspirate, stool or urine reverse transcription-polymerase chain
      reaction (RT-PCR) and/or serological testing were prospectively followed up and
      analyzed. Characteristics of patients admitted to the intensive care unit (ICU)
      and those that were not were compared. RESULTS: Among 47 suspected SARS patients
      with normal chest radiographs, 27 had SARS-associated coronavirus infection
      confirmed by RT-PCR and/or positive serological testing. Twenty-five of the 27
      (93%) patients had HRCT changes compatible with atypical pneumonia, and all 25
      patients developed SARS with progressive clinical deterioration. Ten (40%) had
      unifocal diseases, and 15 had multifocal diseases (60%). Ten (40%) patients had
      the diseases confined to 1 single lung in the first HRCT, and both lungs were
      involved at initial presentation in 15 (60%) patients. Concerning the overall
      extent of the disease at initial presentation, 3 (12%) patients had disease
      process in all lobes, and the disease was confined to 1 single lobe in 10 (40%)
      patients. The disease process was mainly peripheral in location (96%), and the
      lower lobes were more commonly involved (68% in the left lower lobe and 64% in
      the right lower lobe). Small parapneumonic effusions occurred in 1 (4%) patient.
      None of the patients with unifocal lesions or single-lung involvement were
      admitted to the ICU (P < 0.05) (in both comparisons). Subsequent follow-up of the
      2 (7%) patients with normal HRCT on admission showed that they were having
      nonpneumonic SARS-associated coronavirus infection only and were eventually
      denotified from having SARS. CONCLUSIONS: HRCT is useful for early diagnosis of
      SARS-associated coronavirus pneumonia in patients with normal chest radiographs.
      HRCT findings in these patients predict potentially severe disease.

PMID- 14716226
TI  - Aspergillus infection of the airways: computed tomography and pathologic
      findings.
AB  - Aspergillosis is a serious pathologic condition caused by Aspergillus organisms
      and is frequently seen in immunocompromised patients. In recent years, it has
      been shown that Aspergillus infection can result in a broad range of airway
      complications. In this article, we illustrate and review the characteristic
      computed tomography and pathologic findings of the different manifestations of
      Aspergillus infection involving the airways.

PMID- 14716227
TI  - Progression of focal pure ground-glass opacity detected by low-dose helical
      computed tomography screening for lung cancer.
AB  - OBJECTIVE: To clarify the progression of focal pure ground-glass opacity (pGGO)
      detected by low-dose helical computed tomography (CT) screening for lung cancer.
      METHODS: A total of 15,938 low-dose helical CT examinations were performed in
      2052 participants in the screening project, and 1566 of them were judged to have
      yielded abnormal findings requiring further examination. Patients with peripheral
      nodules exhibiting pGGO at the time of the first thin-section CT examination and
      confirmed histologically by thin-section CT after follow-up of more than 6 months
      were enrolled in the current study. Progression was classified based on the
      follow-up thin-section CT findings. RESULTS: The progression of the 8 cases was
      classified into 3 types: increasing size (n = 5: bronchioloalveolar carcinoma
      [BAC]), decreasing size and the appearance of a solid component (n = 2: BAC, n =
      1; adenocarcinoma with mixed subtype [Ad], n = 1), and stable size and increasing
      density (n = 1: BAC). In addition, the decreasing size group was further divided
      into 2 subtypes: a rapid-decreasing type (Ad: n = 1) and a slow-decreasing type
      (BAC: n = 1). The mean period between the first thin-section CT and surgery was
      18 months (range: 7-38 months). All but one of the follow-up cases of lung cancer
      were noninvasive whereas the remaining GGO with a solid component was minimally
      invasive. CONCLUSIONS: The pGGOs of lung cancer nodules do not only increase in
      size or density, but may also decrease rapidly or slowly with the appearance of
      solid components. Close follow-up until the appearance of a solid component may
      be a valid option for the management of pGGO.

PMID- 14716228
TI  - Collateral pathways in thoracic central venous obstruction: three-dimensional
      display using direct spiral computed tomography venography.
AB  - We illustrate the spectrum of venous collateral pathways caused by the thoracic
      central venous obstruction with direct spiral computed tomography (CT) venography
      and 3-dimensional reconstruction images. Venous structures that can be
      demonstrated with CT venography include the jugular veins; the subclavian and
      brachiocephalic (innominate) veins; the internal and lateral thoracic veins; the
      superior and inferior venae cavae; the pericardiophrenic veins; the azygos,
      hemiazygos, and accessory hemiazygos veins; and the intercostal veins.

PMID- 14716229
TI  - Computed tomography in pulmonary artery sarcoma: distinguishing features from
      pulmonary embolic disease.
AB  - OBJECTIVE: The purpose of this study was to present the computed tomography (CT)
      findings of pulmonary artery sarcoma in 7 patients with a focus on the
      distinguishing features of pulmonary embolic disease. METHODS: For the 9 years
      from December 1993 to November 2002, we treated 7 patients with pathologically
      proven pulmonary artery sarcoma, and during the 2 years from December 2000 to
      November 2002, we treated 40 patients with acute (n = 33) or chronic (n = 7)
      pulmonary embolism. In these patients, pulmonary embolism was diagnosed from
      serial CT or clinical findings. Two chest radiologists, blinded to the diagnoses,
      independently reviewed the scans of all 47 patients in random order, and the so
      documented CT features of sarcoma and pulmonary embolism were compared by using
      Fisher exact test or the generalized estimating equations test. RESULTS: The two
      most frequent CT findings of pulmonary artery sarcomas were a low-attenuation
      filling defect occupying the entire luminal diameter of the main (n = 1) or
      proximal (n = 6) pulmonary artery and an expansion of any segment of the
      pulmonary artery with extensive intraluminal filling defect, as observed in six
      (86%) of 7 patients. In contrast, the finding of a lesion occupying the entire
      luminal diameter at the level of proximal pulmonary arteries was absent in all 40
      patients with pulmonary embolism (P < 0.0001) (kappa = 0.9111). Expansion of the
      pulmonary arteries was seen in one (3%) of 40 patients with pulmonary embolism (P
      < 0.0001) (kappa = 0.9108). Extraluminal extension was observed in 5 of 7 (71%)
      patients with sarcoma, but in no patient with an embolism (P < 0.0001) (kappa =
      0.8773). CONCLUSION: CT can help differentiate pulmonary artery sarcoma from
      pulmonary embolism by indicating a low-attenuation filling defect occupying the
      entire luminal diameter of the proximal or main pulmonary artery, expansion of
      the involved arteries, or extraluminal tumor extension.

PMID- 14716230
TI  - Coronary artery calcification scoring by prospectively triggered multidetector
      row computed tomography: is it reproducible?
AB  - The objective of this study was to measure the interobserver and interscan
      variation of coronary artery calcium scores using multidetector-row computed
      tomography (MDCT). Seventy-five patients underwent 2 sequential MDCT scans for
      coronary artery calcification. Each patient's score was separately measured by 3
      blinded radiologists. Scores were treated as discrete and continuous data, and
      independent statistical analysis was performed on all results. There was a high
      proportion of interscan and inter-reader concordance for the presence of coronary
      calcium (range, 0.893-0.973) and for its quantity (range, 0.936-0.988). Overall,
      prospectively triggered multidetector-row calcium scoring is reproducible though
      there is more variation in those patients with already high scores. There is no
      need to scan patients twice at the same sitting.

PMID- 14716231
TI  - 3-dimensional computed tomography lymphography-guided identification of sentinel
      lymph nodes in breast cancer patients using subcutaneous injection of nonionic
      contrast medium: a clinical trial.
AB  - OBJECTIVE: Simple and reliable identification methods for sentinel lymph nodes
      (SLNs) which do not use radioisotope are essential for early breast cancer
      patients in community hospitals in Japan. The purpose of this paper is to
      demonstrate the feasibility and efficacy of computed tomography (CT) lymphography
      for SLN detection. METHODS: The study included 15 cases with T1 or T2 breast
      cancer. After subcutaneous injection of 1 mL of iopamidol in 1 subareolar area of
      the affected breast, CT scanning was carried out and 3-dimensional (3D) CT images
      were created. SLNs predicted from images and CT values were assessed as to
      whether they were identical to those identified by the dye method. RESULTS: An
      enhanced lymph vessel draining into SLN was demonstrated in 11 cases (73%) and an
      enhanced SLN in 10 cases (67%). 3D images clearly revealed the anatomic
      relationship between lymph vessels, SLN, and the surrounding structures. In
      addition, SLN could be predicted by the change of CT value in the time-course in
      another case. In total, SLN in 13 cases (87%) could be predicted. All SLNs
      suggested from CT lymphography were identified by the dye method. No significant
      adverse effect was noted in any case. CONCLUSIONS: The present clinical trial
      indicated that subcutaneous injection of nonionic contrast medium with CT
      scanning seems to be a promising method for the demonstration of a draining lymph
      vessel and SLN. The CT value time-course may also provide some important
      information. Further trials will be needed for the successful establishment of
      this CT lymphography-guided method for SLN identification.

PMID- 14716232
TI  - Niemann-Pick disease: high-resolution CT findings in two siblings.
AB  - Niemann-Pick disease is a rare inherited disorder characterized by deposition of
      sphingomyelin in various organs. We describe the high-resolution computed
      tomography findings in 2 adult sisters with Niemann-Pick disease and extensive
      pulmonary involvement. The main abnormalities consisted of thickening of the
      interlobular septa and patchy areas of ground-glass attenuation.

PMID- 14716233
TI  - Malignant middle cerebral artery infarction in hyperacute ischemic stroke:
      evaluation with multiphasic perfusion computed tomography maps.
AB  - OBJECTIVE: The purpose of this study was to compare the incidence of large
      hypoperfusion (greater than two-thirds of MCA territory) on computed tomography
      (CT) perfusion maps between hyperacute middle cerebral artery (MCA) stroke
      patients without or with malignant cerebral edema. METHODS: Twenty-seven patients
      diagnosed with a hyperacute MCA stroke who had an initial National Institutes of
      Health Stroke Scale (NIHSS) score greater than 10 were included. Multiphasic
      perfusion CT was performed within 6 hours of symptom onset. Patients were divided
      into 2 groups: the malignant group (n = 11), composed of patients who died within
      7 days, and the nonmalignant group, which included all other patients (n = 16).
      Unenhanced CT and CT perfusion maps were assessed and compared between the 2
      groups with special emphasis on examining the CT findings, including hyperdense
      MCA sign, large (greater than two-thirds) hypoattenuation and hypoperfusion in
      the MCA territory, and hypoattenuation in the basal ganglia and other vascular
      territories. RESULTS: The incidence of large hypoattenuation (greater than two
      thirds of MCA territory) on unenhanced CT and large hypoperfusion on CT perfusion
      maps differed significantly between the 2 groups (P < 0.05). Large hypoperfusion
      on the CT total perfusion map was most accurate (93%) among various CT findings
      for the prediction of malignant MCA infarction with high sensitivity (91%),
      specificity (94%), and positive predictive value (91%). CONCLUSIONS: The
      incidence of large hypoperfusion on a CT perfusion map was higher in the
      malignant group than the nonmalignant group. CT perfusion maps may provide added
      information about cerebral perfusion and could be a useful predictor of malignant
      MCA infarction.

PMID- 14716234
TI  - Visual object agnosia and pure word alexia: correlation of functional magnetic
      resonance imaging and lesion localization.
AB  - We present a case of a 64-year-old, right-handed female with a metastatic breast
      cancer lesion involving the left posterior inferior temporal lobe causing
      complete loss of the ability to recognize visually common objects and words.
      After her symptoms resolved on corticosteroid therapy, functional magnetic
      resonance imaging (fMRI) mapping demonstrated strong left-hemispheric dominance
      for word recognition and right-hemispheric dominance for object recognition. The
      case illustrates the relationships among ventral occipito-temporal cortical
      activation, lesion localization, and lesion-induced deficits of higher visual
      function. The relationship between hemispheric dominance determined by fMRI and
      risk of postoperative deficit depends on the specific visual function of
      interest.

PMID- 14716235
TI  - Role of fluid-attenuated inversion recovery in the diagnosis of meningitis:
      comparison with contrast-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: Fluid-attenuated inversion recovery (FLAIR) has shown promise in the
      detection of subarachnoid space disease. The exact role of FLAIR in the diagnosis
      of meningitis has not been established. The purpose of this study was to evaluate
      FLAIR in the detection of meningitis in comparison with contrast-enhanced T1
      weighted images (T1WI) in a blinded-reader study. We describe hyperintense sulci
      (HS) on FLAIR sequence in meningitis in relation to cerebrospinal fluid (CSF)
      protein and effective echo time (TE). METHODS: Two observers blinded to clinical
      information reviewed magnetic resonance (MR) images of patients with the
      diagnosis of meningitis and those of age-matched controls. The diagnosis was
      confirmed from chart review and CSF results. FLAIR images were obtained with 2
      different TE values of 120 milliseconds and 150 milliseconds. FLAIR changes were
      correlated with CSF protein concentration and contrast-enhanced T1WI. RESULTS:
      Twenty-eight MR images of meningitis patients were reviewed. There were 23
      abnormal MR images including 16 abnormal FLAIR scans with hyperintense sulci and
      23 with leptomeningeal enhancement on contrast-enhanced T1WI. HS on FLAIR
      correlated with leptomeningeal enhancement on contrast-enhanced T1WI. Four viral
      and 1 bacterial meningitis had normal MR images (FLAIR and postcontrast TIWI).
      Two different TE values were used: 120 milliseconds (n = 15) and 150 milliseconds
      (n = 13). All patients with effective TE of 150 milliseconds. and CSF protein of
      more than 132 mg/dL had hyperintense sulci whereas patients with effective TE of
      120 milliseconds and CSF protein of 257 mg/dL or more had HS. CONCLUSIONS: The
      sensitivity of contrast-enhanced T1WI was higher than FLAIR. HS on FLAIR
      correlated with contrast enhancement on T1WI. However, the sensitivity of FLAIR
      depends on CSF protein concentration threshold for (CSF hyperintensity) for a
      given effective TE. FLAIR cannot replace contrast-enhanced T1WI in diagnosing
      meningitis.

PMID- 14716237
TI  - Evaluation of extraocular muscles in the edematous phase of Graves ophthalmopathy
      on contrast-enhanced fat-suppressed magnetic resonance imaging.
AB  - OBJECTIVE: Extraocular muscles (EOMs) reveal characteristic contrast-enhancement
      patterns on magnetic resonance (MR) imaging due to their rich vascular supply.
      The objective of this study was to evaluate contrast-enhancement patterns of EOMs
      in patients with edematous phase of Graves ophthalmopathy (GO) using contrast
      enhanced fat-suppressed MR imaging in comparison with normal volunteers. METHODS:
      EOMs of 15 patients with edematous phase of GO and those of 15 normal volunteers
      were evaluated using coronal T1-weighted MR images with fat suppression before
      and after intravenous administration of gadolinium. The image sequence was a fast
      spin-echo with chemical shift selective fat saturation. The degree of contrast
      enhancement for EOMs and temporal muscles (TMs) was assessed via a 4-step grading
      system and by 2 reviewers. RESULTS: There were statistically significant
      differences for the degrees of contrast enhancement in all EOMs between the
      patients with GO and normal volunteers. The degrees of contrast enhancement for
      all EOMs were significantly decreased in patients with edematous phase of GO.
      CONCLUSIONS: The microcirculation within the EOMs tends to be impaired during the
      progress of disease, and the MR imaging pattern gives a semiquantitative
      measurement of the microcirculatory impairment of the EOMs during the edematous
      phase of the disease.

PMID- 14716236
TI  - Magnetic resonance imaging of synovial proliferation in temporomandibular
      disorders with pain.
AB  - OBJECTIVE: The objective of this study was to assess the clinical significance of
      synovial proliferation in patients with painful temporomandibular disorders based
      on magnetic resonance imaging findings. METHODS: The current study was conducted
      in 100 joints of 100 patients with unilateral painful temporomandibular
      disorders. One hundred joints on the contralateral side of patients with
      unilateral disease were used as nonpain group. Areas in the articular space that
      showed a low signal intensity on T1-weighted imaging, a high signal intensity on
      T2-weighted imaging, and high signal intensity on gadolinium-enhanced fat
      suppressed T1-weighted imaging were judged to be regions of synovial
      proliferation. RESULTS: Synovial proliferation alone was observed in 8.0% of the
      pain group, but in none of the nonpain group. Synovial proliferation + effusion
      was observed in 33.0% of the pain group and in 7.0% of the nonpain group.
      Effusion alone was observed in 7.0% of the pain group and in 3.0% of the nonpain
      group. The mean visual analog scale value of pain was in the order of synovial
      proliferation alone > synovial proliferation + effusion > effusion alone. The
      incidence rates of anterior displacement of the disk were 100% for synovial
      proliferation alone, 93.9% for synovial proliferation + effusion, 57.1% for
      effusion alone, and 57.7% for "without synovial proliferation/effusion."
      CONCLUSIONS: Strong correlations were observed between synovial proliferation,
      pain, and disk displacement. It is considered that evaluating effusion alone
      provides only limited information on the disease state in painful
      temporomandibular disorders. Thus, it is essential to include enhanced T1
      weighted imaging as a means to judge the disease state as well as to assess
      disease progression.

PMID- 14716238
TI  - Prenatal magnetic resonance imaging evaluation of ischemic brain lesions in the
      survivors of monochorionic twin pregnancies: report of 3 cases.
AB  - The death of 1 twin of monochorionic pairs is associated with a significant risk
      of brain hypoxic-ischemic damage in the survivor. Ultrasound may diagnose
      cerebral anomalies only a few weeks after the event. We report 3 cases of single
      survivors of monochorionic-twin pregnancies in which prenatal magnetic resonance
      imaging detected brain changes earlier and with better definition of the brain
      abnormalities than ultrasound.

PMID- 14716239
TI  - Maple syrup urine disease: diffusion-weighted and diffusion-tensor magnetic
      resonance imaging findings.
AB  - We present conventional magnetic resonance (MR) imaging with diffusion-weighted
      and diffusion-tensor imaging findings in a 10-day-old neonate with maple syrup
      urine disease (MSUD). On conventional MR imaging, signal abnormalities were noted
      in the affected white matter of cerebellum, dorsal brainstem, thalami, posterior
      limbs of internal capsules, and the corona radiata. These regions showed marked
      hyperintensity on diffusion-weighted images with decreased apparent diffusion
      coefficient values (average 68% reduction). Diffusion-tensor imaging showed
      decreased anisotropy (average 57% reduction) in the corresponding areas. Both
      diffusion-weighted and diffusion-tensor imaging are valuable in the diagnosis and
      understanding of the pathogenesis of MSUD, with findings that suggest cytotoxic
      edema and damaged oligodendro-axonal units within the affected white matter.

PMID- 14716240
TI  - Glutaric aciduria type I: value of diffusion-weighted magnetic resonance imaging
      for diagnosing acute striatal necrosis.
AB  - Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by
      deficiency of glutaryl-CoA dehydrogenase. We report the cranial computed
      tomography (CT) and magnetic resonance (MR) imaging findings in a 5-month-old
      girl with this disorder who presented with an acute dystonic syndrome. CT
      findings demonstrated only subtle loss of attenuation in the basal ganglia, MR
      spectroscopy was normal, and conventional MR images showed increased T2-signal
      limited to the putamina. Diffusion-weighted MR imaging demonstrated more
      extensive disease than was apparent either on CT or on the conventional MR
      images, including bilateral involvement of the putamina, globus pallidus, and
      caudate nuclei, consistent with acute necrosis of the corpus striatum and
      lentiform nuclei.

PMID- 14716241
TI  - Subacute sclerosing panencephalitis with pontine involvement.
AB  - In subacute sclerosing panencephalitis, brainstem involvement is rare. This paper
      reports an 11-year-old boy with the disease with prominent pontine involvement.
      Diffusion magnetic resonance imaging had superior information with respect to
      involvement of the nerve fibers. In the ventral part of the pons, the regions
      containing the longitudinal pontine nerve bundles were spared bilaterally and
      symmetrically. The pontine tegmentum was also spared. High signal in the affected
      regions was revealed by b = 1000 s/mm2 images. The apparent diffusion coefficient
      values in these regions were low, ranging between 0.43 x 10(-3) to 0.54 x 10(-3)
      mm2/s. Those of the spared tegmentum and longitudinal bundles were normal,
      ranging between 0.89 x 10(-3) to 1.04 x 10(-3) mm2/s, compared with the values
      from the normal-appearing regions of the cerebellar parenchyma.

PMID- 14716242
TI  - Role of proton magnetic resonance spectroscopy in the diagnosis of gliomatosis
      cerebri: a unique pattern of normal choline but elevated Myo-inositol metabolite
      levels.
AB  - A patient with histologically proven gliomatosis cerebri presented with a normal
      choline level but a markedly abnormal elevated myo-inositol level on magnetic
      resonance (MR) spectroscopy. We describe the case presentation, imaging findings
      (in particular, the unique MR spectroscopic pattern), and their significance
      regarding the diagnosis of this relatively rare neoplasm.

PMID- 14716243
TI  - Multidetector-row computed tomography and 3-dimensional computed tomography
      imaging of small bowel neoplasms: current concept in diagnosis.
AB  - The diagnosis of small bowel neoplasms can present a difficult challenge to the
      radiologist because the tumors are uncommon, often small, and may be difficult to
      detect radiographically. The most common small bowel neoplasms include
      adenocarcinoma, carcinoid, lymphoma, and gastrointestinal stromal tumors. The
      location and computed tomography (CT) appearance of the small bowel tumors may
      aid in the diagnosis. For instance, small bowel adenocarcinoma occurs more
      frequently in the duodenum and may result in obstruction. Carcinoid tumors are
      more common in the ileum and are typically hypervascular submucosal masses that
      produce a characteristic mesenteric mass when they spread to the mesenteric
      nodes. Lymphoma can occur anywhere along the gastrointestinal tract and have a
      variable CT appearance. It may appear as a single mass, multiple masses, an
      infiltrating lesion resulting in aneurysmal dilatation of the bowel, or as an
      exophytic mass. Gastrointestinal stromal tumors are more common in the jejunum
      and ileum and usually appear exophytic and bulky often with ulceration.
      Traditionally, small bowel series and enteroclysis have been used for imaging
      patients with suspected small bowel tumors. More recently, CT is beginning to
      play a more important role for this clinical indication. The thinner collimation
      possible with multidetector CT (MDCT) along with water as oral contrast and a
      good intravenous contrast bolus may improve the sensitivity of CT for detecting
      small bowel tumors. In addition, MDCT scanners improve the quality of the 3
      dimensional CT (3D CT) images that are valuable to the clinicians and surgeons
      for surgical planning. It is important for the radiologist to be familiar with
      the CT appearance of these neoplasms and the potential role of MDCT and 3D
      imaging in their diagnosis and surgical planning.

PMID- 14716244
TI  - Natural history of pancreatic intraductal papillary mucinous tumor of branch duct
      type: follow-up study by magnetic resonance cholangiopancreatography.
AB  - OBJECTIVE: The purpose of this study was to elucidate the natural history of
      branch duct type pancreatic intraductal papillary mucinous tumor (IPMT) by
      evaluating serial changes in the magnetic resonance cholangiopancreatography
      (MRCP) findings of patients diagnosed with pancreatic IPMT of branch duct type.
      METHODS: Thirty-five patients had branch duct type IPMT, including 9 patients
      with separate lesions, and underwent initial and follow-up MRCP over a period of
      more than 12 months. The maximum diameter of the cystic lesion, the presence of
      associated main pancreatic duct (MPD) dilatation, and the presence of a filling
      defect were evaluated. Serial changes in these findings were analyzed. RESULTS:
      Tumor enlargement on follow-up MRCP was observed in 7 cases. Of the 29 branch
      duct IPMTs without associated MPD dilatation or a filling defect identified on
      initial MRCP, only 1 showed gradual tumor enlargement. In 4 cases, the cyst size
      decreased on follow-up MRCP. CONCLUSIONS: Branch duct type IPMTs grow slowly and
      can be monitored without operation provided that the tumor shows no associated
      MPD dilatation or filling defect.

PMID- 14716245
TI  - Local staging of rectal cancer: assessment with double-contrast multislice
      computed tomography and transrectal ultrasound.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of multislice
      computed tomography (MSCT) with double-contrast technique and transrectal
      ultrasound (TRUS) in staging of rectal carcinoma compared with histopathological
      confirmation. METHODS: In a prospective study of 92 patients with rectal
      carcinoma, preoperative MSCT with negative rectal contrast (methylcellulose) and
      intravenous contrast was performed. Reconstructions in 3 planes were analyzed in
      a cine mode in picture archiving and communication (PAC) system. Analysis of
      rectal wall infiltration was performed preoperatively according to a modified
      tumor, nodes, metastases (TNM)-classification system (< or =T2/T3/T4, N0/N+,
      UICC/UICC I > I). MSCT imaging findings were compared with the results of TRUS
      and histopathology in all patients. RESULTS: With interactive multiplanar image
      viewing, the results of MSCT of depth of rectal wall invasion (T-staging) were as
      follows: sensitivity, specificity, positive and negative predictive values, and
      accuracy rate were 85%, 87%, 88%, 84%, and 86% (54/63 patients) compared with
      59%, 63%, 72%, 48%, and 60% (38/63 patients), respectively, for TRUS staging in
      the same patients. The sensitivity, specificity, positive and negative predictive
      values, and accuracy rate of MSCT for perirectal nodes evaluation was 75%, 85%,
      75%, 85%, and 81% (51/63 patients) compared with 55%, 71%, 50%, 74%, and 65%
      (41/63 patients), respectively, for TRUS in detecting metastatic lymph nodes.
      CONCLUSIONS: Preoperative double-contrast MSCT accurately indicates the exact
      depth of tumor infiltration and improves lymph node staging. The new technical
      innovations of MSCT provide superior information for preoperative staging of
      rectal cancer and may compete with TRUS as the standard preoperative diagnostic
      method.

PMID- 14716246
TI  - Computed tomography and magnetic resonance imaging of inferior vena caval
      thrombus associated with metastasis to the kidney.
AB  - The computed tomography and magnetic resonance imaging findings in 2 cases of
      inferior vena caval thrombus associated with metastases to the kidney are
      presented. In both cases, the radiologic findings were suggestive of renal cell
      carcinoma. Recognition that metastases to the kidney can be associated with
      inferior vena caval thrombus broadens the differential diagnosis in a patient
      with a renal mass, an inferior vena caval filling defect, and a known primary
      malignancy, potentially altering the diagnostic approach.

PMID- 14716247
TI  - Measurement of trabecular bone mineral density in the thoracic spine using
      cardiac gated quantitative computed tomography.
AB  - OBJECTIVES: To develop a method and evaluate the performance of thoracic bone
      mineral density (BMD) measurement using cardiac gated quantitative computed
      tomography (QCT). METHODS: A total of 762 participants (57% female) with a mean
      age of 61 years had a CT examination of the heart using prospective cardiac
      gating. A subset of 443 participants had replicate CT examinations of the heart.
      Another, nonindependent subset of 464 participants had CT examination of the
      abdomen. A QCT calibration phantom was included in all scans. Trabecular BMD was
      measured in the thoracic (T6-T11) and lumbar (T11-L4) spine. Tests of calibration
      and refinement and simple correlations between replicate thoracic BMD
      measurements and between thoracic and lumbar BMD measurements were calculated.
      RESULTS: There was high correlation between replicated thoracic BMD measurements
      in men (r = 0.995, P < 0.0001) and in women (r = 0.995, P < 0.0001). There was
      high correlation between thoracic and lumbar BMD in men (r = 0.90, P < 0.0001)
      and in women (r = 0.94, P < 0.0001). The mean BMD was higher in the thoracic
      spine than the lumbar spine in men (137.58 mg/cm3 vs. 126.94 mg/cm3, P < 0.0001)
      and in women (152.07 mg/cm3 vs. 133.44 mg/cm3, P < 0.0001). In both genders,
      thoracic and lumbar BMD was inversely associated with age (all P < 0.05).
      CONCLUSIONS: Cardiac gated CT, primarily intended for measurement of coronary
      vascular calcium, can be used to measure thoracic BMD with high precision.
      Thoracic BMD measurements using this method are highly correlated with QCT
      measurements in the lumbar spine.

PMID- 14716248
TI  - Synovial sarcoma of the soft tissues: prognostic significance of imaging
      features.
AB  - OBJECTIVE: This study assessed the prognostic value of computed tomography (CT)
      and magnetic resonance (MR) imaging features in synovial sarcoma of the soft
      tissues. METHODS: CT and MR imaging studies were performed in 30 patients with
      pathologically confirmed synovial sarcoma of the soft tissues. CT and MR imaging
      findings obtained by 2 radiologists with agreement by consensus were compared for
      histopathologic features including tumor grade. Univariate analyses were
      conducted to clarify the impact of imaging findings on overall survival with a
      medium duration of 32 months. Multivariate analysis was estimated using a Cox
      proportional hazards model with the relative risk of each variable. RESULTS:
      Statistically significant imaging findings favoring a diagnosis of high-grade
      tumor included proximal distribution (P < 0.01), large tumor size (>10 cm, P <
      0.05), the absence of calcification (P < 0.05), tumor possessing cyst (P < 0.01),
      the presence of hemorrhage (P < 0.05), and the presence of triple signal pattern
      (P < 0.05). Univariate analysis showed that proximal distribution (P < 0.05),
      tumor size larger than 5 cm (P < 0.01), the absence of calcification (P < 0.01),
      the presence of hemorrhage (P < 0.05), and the presence of triple signal pattern
      (P < 0.05) had a significant association with the disease-free survival (DFS).
      Multiple logistic regression models revealed that tumor size larger than 10 cm
      had a significant impact on the DFS with relative risk of 18.8 (P < 0.05).
      CONCLUSION: CT and MR imaging studies allow prognosis prediction in patients with
      synovial sarcoma of the soft tissues.

PMID- 14716249
TI  - Admissions committees select our future dental professionals. Right?

PMID- 14716250
TI  - Posttraumatic stress disorder: psychopathology, medical management, and dental
      implications.
AB  - PTSD is a chronic mental illness that may arise after an individual experiences
      or witnesses a life-threatening event. Symptoms consist of persistent
      reexperiencing of the event, avoidance of reminders of the event, a numbing of
      positive emotions, and social withdrawal. A depressed mood and excessive use of
      alcohol and tobacco may accompany the disorder. PTSD afflicts approximately 5% of
      men and 11% of women. Dental disease may be extensive because of neglect of oral
      hygiene compounded by cigarette smoking. Dental treatment includes preventive
      education, oral cancer screening, and prescribing saliva substitutes or
      stimulants and anticaries agents to combat medication-induced xerostomia.
      Precautions must be taken when prescribing or administering certain analgesics,
      antibiotics, or sedative agents that may adversely interact with the psychiatric
      medications or when performing surgery because of the long-term effects of
      alcohol abuse.

PMID- 14716251
TI  - Blood-flow and neurosensory changes in the maxillary dental pulp after differing
      Le Fort I osteotomies.
AB  - PURPOSE: The objective of this study was to examine changes in blood flow and the
      recovery of sensibility in the maxillary dental pulp after two different types of
      maxillary osteotomies. Study design Nine patients (C-group) who underwent a
      combined of Le Fort I and horseshoe osteotomy and 14 patients (NC-group) who
      underwent a single-segment Le Fort I osteotomy were compared. Thirty-two (C
      group) and 54 (NC-group) maxillary incisors were examined preoperatively and at 1
      7 days, 14 days, and 3, 6, 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: In both groups, the PBF dropped
      to its lowest value at 1 day after surgery and increased thereafter. Though a
      temporary drop of the PBF was observed in the NC-group on day 4, the PS recovered
      earlier in the NC-group than in the C-group. CONCLUSION: These results suggest
      that the method of maxillary osteotomy influences the postoperative change of the
      PBF and recovery of the PS in the maxillary teeth.

PMID- 14716252
TI  - Diagnostic significance of carbamazepine and trigger zones in trigeminal
      neuralgia.
AB  - OBJECTIVE: To investigate the relationship between the efficacy of carbamazepine
      (CBZ) and the presence of the trigger zone for diagnosis of trigeminal neuralgia
      (TN). Study design CBZ was administered to 61 patients with suspected TN. All
      patients underwent intracranial examination by magnetic resonance imaging or
      computed tomography. The final diagnosis was established by oral and
      maxillofacial surgeon and neurosurgeon. RESULTS: Of the 61 patients, 50 were
      finally diagnosed as having TN and 6 as having atypical facial pain. CBZ was
      effective for pain relief in 45 of the 50 TN patients (90%), and in 5 of the 11
      patients (45%) with other diseases (P <.005). However, CBZ also relieved pain in
      some patients other than TN. Thirty of the 31 patients (97%) with a distinct
      trigger zone and 20 of the 30 (67%) without a trigger zone were diagnosed as
      having TN (P<0.005). CONCLUSION: The efficacy of CBZ is an auxiliary indicator of
      TN and the presence of a distinct trigger zone is a strong indicator of TN.

PMID- 14716253
TI  - Maxillofacial fractures sustained during sports played with a ball.
AB  - OBJECTIVE: The aim of this study was to investigate the incidence and type of
      maxillofacial fractures caused by various sports played with a ball to better
      understand the nature of these fractures. Study design Retrospective study was
      carried out using records from 100 patients treated between 1986-2002. Age and
      sex, etiology, and site of the fracture, yearly and monthly distribution of the
      fractures, and treatment modality were analyzed. RESULTS: The fractures mostly
      resulted from baseball (44%), followed by rugby (28%) and soccer (18%). The
      highest incidence was in the 10- to 19-year age-group with male propensity. The
      most common cause of the fractures was impact against another player (43%). The
      majority of the patients suffered from mandibular fractures (56%), followed by
      midface (31%) and alveolar fractures (12%). Mandibular angle, zygoma, and
      zygomatic arch fractures were prominent for rugby fractures. A yearly comparison
      of the fracture incidence showed a gradual decrease over the 16-year period.
      Fractures had a peak incidence in autumn. 55% of the patients were treated
      surgically. Surgical intervention was mostly needed for patients sustaining
      fractures during soccer (72.2%). CONCLUSIONS: Among ball-related sports, baseball
      is responsible for most of the maxillofacial fractures, but, although the
      incidence is not that high, soccer-related fractures may be more severe due to
      the nature of this sport.

PMID- 14716254
TI  - An update of the etiology and management of xerostomia.
AB  - Salivary gland disease gives rise to salivary gland enlargement, pain, and
      prolonged xerostomia (dry mouth). Xerostomia is the most common long-standing
      problem for the majority of affected patients. There are many causes of dry
      mouth, with long-standing xerostomia being a particular problem in Sjogren's
      syndrome and after radiation to the head and neck region. Xerostomia is usually
      managed with saliva substitutes, but a large number of potential systemic
      therapies of long-standing xerostomia now exist. Some-particularly
      immunosuppressants-are of fundamental interest for the potential reduction of
      gland damage in Sjogren's syndrome but as yet are of limited clinical usefulness.
      Others, particularly pilocarpine and cevimeline, are, or have the potential to
      be, clinically useful in stimulating salivation by virtue of their action on
      cholinergic receptors.

PMID- 14716255
TI  - Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients
      receiving radiation for head and neck cancer.
AB  - Oropharyngeal candidiasis (OPC) is relatively common in patients receiving
      radiation for head and neck cancer occurring in approximately 25% of patients.
      Candida albicans has been described as the primary infecting organism. Recently,
      other organisms, particularly Candida glabrata, have emerged as causative agents
      of OPC among immunocompromised patients. This study describes the characteristics
      of 6 patients with head and neck cancer treated with radiotherapy at our
      institution, who were found to have Candida glabrata-associated OPC and their
      responses to oral fluconazole. All 6 patients were successfully treated with oral
      fluconazole. However, most did not respond to the usual dose of 100 mg/day
      necessitating doses ranging from 200 to 800 mg/day to achieve clinical cure. All
      3 patients receiving radiation only were successfully treated with up to 200
      mg/day; 2 of 3 patients receiving concomitant chemoradiation required doses
      ranging from 400 to 800 mg/day. As with systemic infection, previous fluconazole
      use appears to be a risk factor for this infection, but not with all patients.

PMID- 14716256
TI  - Benign cementoblastoma involving multiple maxillary teeth: report of a case with
      a review of the literature.
AB  - A rare case of benign cementoblastoma involving multiple deciduous and permanent
      teeth is presented with a review of the literature. A 12-year-old boy was
      admitted for a swelling in the right maxillary premolar-molar region. A
      radiologic examination revealed a well-defined, round, radiopaque mass extending
      from the right maxillary first premolar to the second permanent molar. The tumor
      was removed with all associated teeth. A histologic examination of the surgical
      specimen revealed a well-circumscribed tumor composed of cementum-like tissue
      surrounded by a fibrous capsule. The tumor was attached to the roots of the
      second deciduous molar, first premolar, and the first and second permanent molars
      and embedded in the crown and root of the right maxillary second premolar,
      suggesting that the lesion had arisen from the second deciduous molar. There has
      been no recurrence of the lesion more than 18 months after the surgical
      procedure.

PMID- 14716257
TI  - Comparative immunohistochemical study of the presence of mast cells in apical
      granulomas and periapical cysts: possible role of mast cells in the course of
      human periapical lesions.
AB  - Cells other than macrophages and lymphocytes have recently been shown capable of
      producing cytokines and mediators. Among these are mast cells, a cell population
      now recognized for its immunoregulatory properties. Little is known about the
      complex interactions between cells, cytokines, and other inflammatory elements in
      periapical lesions. The objective of this investigation was to determine the
      immunohistochemical pattern of expression of mast cells tryptase in periapical
      lesions based on study of 20 apical granulomas and 20 periapical cysts.
      Microscopic analysis revealed mast cells to be present in greater numbers in
      periapical cysts than in apical granulomas, and in cysts were more numerous in
      regions of active inflammation. Mast cells tended to be more common in the
      peripheral regions of both periapical lesions, and were often found in close
      proximity to lymphocytes. These findings lead us to propose a functional
      relationship between these two cell populations that may facilitate elicitation
      of an immune response contributory to the pathogenesis of periapical lesions.

PMID- 14716258
TI  - Elastofibroma: the initial report in the oral mucosa.
AB  - Elastofibroma is a well known pseudotumorous process that characteristically
      occurs in the scapular region in the presence of trauma or injury. Additionally,
      numerous other sites of origin have been reported in the literature, but to date
      none have presented in the oral cavity. A 56-year-old female presented with a
      painless small mass in the floor of the mouth. A longstanding history of trauma
      to the region was noted. Histopathologic examination revealed the mass to be
      comprised of a haphazard array of collagen and elastic fibers in a myxomatous
      background. The elastic nature of the fibers was confirmed by an elastic stain.
      The diagnosis of elastofibroma was rendered based upon the microscopic findings.
      This represents the first reported case of elastofibroma of the oral cavity.

PMID- 14716259
TI  - Localized jaw enlargement in renal osteodystrophy: report of a case and review of
      the literature.
AB  - Renal osteodystrophy is a common long-term complication of end-stage renal
      disease. Involvement of the jaws is common and radiographic alterations are often
      one of the earliest signs of chronic renal disease. However, marked enlargement
      of the jaws is a rare complication of renal osteodystrophy. A case of localized
      asymptomatic enlargement of the mandible in a 38-year-old woman with chronic
      renal failure is presented. The clinical, radiographic, and histological findings
      were consistent with renal osteodystrophy. To our knowledge, this is the third
      case of localized mandibular enlargement of renal osteodystrophy reported in the
      English-language literature.

PMID- 14716260
TI  - Rare vascular proliferations of the oral mucosa.
AB  - Benign vascular lesions-malformative, reactive, and neoplastic-are fairly common
      in the oral soft tissues; nevertheless, extravascular papillary endothelial
      hyperplasia and sinusoidal hemangioma have not been reported in this location. To
      our knowledge, a single case of intraoral spindle cell hemangioma has appeared in
      the literature. This report deals with histopathological features of these rare
      vascular proliferations involving the oral mucosa.

PMID- 14716261
TI  - In vitro evaluation of the antimicrobial activity of chlorhexidine and sodium
      hypochlorite.
AB  - The aim of this study was to investigate in vitro the antimicrobial activity of
      0.2%, 1%, and 2% chlorhexidine gluconate (CHX gel and CHX liquid), against
      endodontic pathogens and compare the results with the ones achieved by 0.5%, 1%,
      2.5%, 4%, and 5.25% sodium hypochlorite (NaOCl). A broth dilution test was
      performed, and the timing for irrigants to kill microbial cells was recorded and
      statistically analyzed. Both 2.0% gel and liquid formulations eliminated
      Staphylococcus aureus and Candida albicans in 15 seconds, whereas the gel
      formulation killed Enterococcus faecalis in 1 minute. All tested irrigants
      eliminated Porphyromonas endodontalis, Porphyromonas gingivalis, and Prevotella
      intermedia in 15 seconds. The timing required for 1.0% and 2.0% CHX liquid to
      eliminate all microorganisms was the same required for 5.25% NaOCl. The
      antimicrobial action is related to type, concentration, and presentation form of
      the irrigants as well as the microbial susceptibility.

PMID- 14716262
TI  - Polymerase chain reaction-based analysis of microorganisms associated with failed
      endodontic treatment.
AB  - OBJECTIVE: In this study, we aimed to investigate the occurrence of several
      microbial species in cases of failed endodontic therapy by means of the
      polymerase chain reaction (PCR). Study design Root canal samples were taken from
      22 root-filled teeth with persistent periradicular lesions selected for re
      treatment. DNA was extracted from the samples and analyzed for the presence of 19
      microbial taxa by using the polymerase chain reaction. RESULTS: All samples were
      positive for at least 1 of the target microbial species. Enterococcus faecalis
      was the most prevalent species-detected in 77% of the cases. The other most
      prevalent species were Pseudoramibacter alactolyticus (52%), Propionibacterium
      propionicum (52%), Dialister pneumosintes (48%), and Filifactor alocis (48%).
      Candida albicans was found in 9% of the samples. The mean number of species in
      samples filled up to 2 mm short of the radiographic apex was 3 (range, 1-5),
      whereas cases in which the filling was greater than 2 mm from the apex yielded a
      mean of 5 species (range, 2-11). This difference was statistically significant (P
      <.05). CONCLUSIONS: Microorganisms occurred in all cases of root-filled teeth
      associated with periradicular lesions, which lends strong support to the
      assertion that treatment failures are rather of infectious etiology, caused by
      persistent or secondary intraradicular infections. E faecalis was the most
      prevalent species, followed by 4 other anaerobic species: P. alactolyticus, P.
      propionicum, D. pneumosintes, and F. alocis. All examined samples harbored at
      least 1 of the following gram-positive bacterial species: E. faecalis, P.
      alactolyticus, or P. propionicum.

PMID- 14716263
TI  - Success rate of endodontic treatment of teeth with vital and nonvital pulps. A
      meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to use meta-analysis statistics to
      determine the influence of factors such as apical limit (short vs.
      overextension), status of the pulp (vital vs. nonvital), and periapical status
      (presence or absence of radiolucency) on endodontic prognosis. Study design The
      study-list was obtained by using a MEDLINE search and Japana Centra Revuo
      Medicina search. Only those papers in which the criteria for success or failure
      was exactly described were accepted. RESULTS: The cumulative success rate of 82.8
      +/- 1.19% (average +/-95% confidence interval) was obtained for vital pulp; and
      78.9 +/- 1.05%, for nonvital ones. There was a significant difference between the
      2 groups.The cumulative success rates with overextension, flush, and
      underextension in vital teeth were 70.8 +/- 1.44, 86.5 +/- 0.88, and 85.5 +/-
      0.98% respectively. There was a significant difference between flush and
      overextension and between flush and underextension. The rates for nonvital pulp
      were similar to those for vital ones. CONCLUSION: The root canal should be filled
      to within 2 mm of the radiographic apex.

PMID- 14716264
TI  - The effect of Emdogain gel on periodontal healing in replanted monkeys' teeth.
AB  - OBJECTIVE: We sought to histologically evaluate the effect of Emdogain gel on
      periodontal healing in monkeys' teeth undergoing delayed replantation. Study
      design Mature monkey teeth simulating avulsion were endodontically treated before
      extraction. Negative control teeth (group N = 10 roots) underwent immediate
      replantation, whereas the rest were bench-dried for 1 hour and treated in one of
      the following ways before replantation: the positive control teeth (group P = 12
      roots) had no further treatment; group C teeth (4 roots) had the periodontal
      ligament removed; group D teeth (10 roots) were treated with Emdogain gel; group
      E teeth (6 roots) had the periodontal ligament removed before the application of
      Emdogain gel; and group F teeth (7 roots) had the periodontal ligament removed,
      the root surface conditioned, and Emdogain gel applied. Periodontal healing was
      evaluated after 16 weeks by undertaking histomorphometric analysis. RESULTS: The
      Kruskal-Wallis and Mann-Whitney U tests revealed that group N teeth had a
      statistically higher occurrence of complete healing than did all other groups,
      whereas group P was not significantly different in any of the healing categories
      from D, E, and F, the groups in which Emdogain gel was used. Group C teeth had a
      significantly higher occurrence of replacement root resorption than did the teeth
      in groups P and F-but were not significantly different from teeth in groups D and
      E. CONCLUSION: Emdogain gel did not appear to significantly reduce replacement
      resorption in monkeys' teeth that had undergone delayed replantation.

PMID- 14716265
TI  - Influence of the thickness of mineral trioxide aggregate on sealing ability of
      root-end fillings in vitro.
AB  - The purpose of this study was to compare the ability of different thicknesses of
      mineral trioxide aggregate (MTA) to prevent apical leakage through the use of a
      protein-dye complex with Coomassie Brilliant Blue G. Sixty-four teeth were
      divided into 4 groups, then filled with MTA to depths of 1, 2, 3, or 4 mm. Two
      teeth served as the positive controls. Another 2 teeth served as the negative
      controls. Root-filled teeth were mounted in an apparatus and then challenged with
      protein solution. The evaluation was conduced at 24-hour intervals for 60 days.
      The 1-mm-thick MTA was the least effective in preventing apical leakage (P <.05).
      No significance difference was found between 2- and 3-mm-thick MTA (P >.05). Four
      millimeter-thick MTA was significantly more effective than the other thicknesses
      tested (P <.05). The results of this study suggest that the thickness of 4 mm is
      most adequate for the use of MTA as a root-end filling material.

PMID- 14716266
TI  - A comparison of Profile, Hero 642, and K3 instrumentation systems in teeth using
      digital imaging analysis.
AB  - OBJECTIVE: To evaluate the changes in cross-sectional area morphology of curved
      canals after instrumentation with Profile((R)), Hero 642((R)), and K3((R)) using
      digital imaging analysis. Study design Thirty mesial mandibular curved canals
      were used (25-40 degrees ). The molars were embedded in resin and the roots were
      sectioned transversely at three levels: apical, middle, and coronal. The canals
      were randomly distributed into 3 groups for instrumentation using Profile.04
      and.06, Hero 642, and K3. The pre- and postinstrumentation sections were
      digitized and areas corresponding to the canals were measured with image
      processing software. RESULTS: Hero eliminated significantly more dentine than K3
      and Profile in all 3 sections (P <.01, ANOVA test), with no differences observed
      between the latter 2 systems (P >.05, Student-Newman-Keuls test). All 3 systems
      yielded a rounded canal morphology in the coronal, middle, and apical thirds.
      CONCLUSION: Hero rotary instruments produced more changes in cross-sectional area
      of the root canal.

PMID- 14716267
TI  - Evaluation of disc position in edentulous patients with complete dentures.
AB  - OBJECTIVE: This study evaluated the condyle-disc relationship on magnetic
      resonance image (MRI) in a group of subjects with silent temporomandibular joints
      (TMJs) when tested clinically with those in subjects with discernible
      temporomandibular sounds. Study design Twenty-five completely edentulous patients
      were selected to participate in this study. The study was based on bilateral MRIs
      of 15 patients (with articular sound) and 10 symptom-free volunteers (control).
      RESULTS: It was noted that disc displacement was found in 45% of the TMJs with no
      history of articular sounds. In 6 TMJs of control group, a reducing disc
      displacement was found, and in 3 TMJs a permanent displacement was found. Disc
      displacements were identified in 70% of patients. Reducing disc displacement was
      found in 19 of these TMJs, whereas permanent displacement was found in 2 TMJs. In
      9 of the joints of the symptomatic group, a superior disc position was found.
      Also verified was a significant association between reducing disc displacement
      and biconvex disc. CONCLUSION: These observations demonstrated that internal
      derangements can not be associated to clicking joints or symptoms of
      temporomandibular disorders in elderly edentulous patients, and the presence of
      displaced discs seems to be associated to altered disc morphology, but not to
      osseous abnormalities.

PMID- 14716268
TI  - Schwannoma of the mental nerve: usefulness of preoperative imaging: a case
      report.
AB  - Schwannoma of the head and neck region is relatively uncommon. We report a case
      of schwannoma arising from the left mental nerve. A 21-year-old male presented at
      our hospital with a painless swelling of the left cheek. Because the lesion had
      rapidly increased in size, a malignant tumor was suspected. Magnetic resonance
      imaging (MRI), computed tomography, and ultrasonography were performed. MRI and
      ultrasonography revealed that the tumor was connected to the mental nerve. Both
      MRI and ultrasonography were found to be useful in making a preoperative
      diagnosis. It was possible to determine prior to surgery that this was a
      peripheral nerve sheath tumor. The lesion was completely resected. The
      pathological diagnosis was Antoni type A schwannoma. There has been no sign of
      recurrence 1 year after surgery.

PMID- 14716269
TI  - Biometric and magnetic resonance imaging assessment of dentofacial abnormalities
      in a case of Klippel-Trenaunay-Weber syndrome.
AB  - Klippel-Trenaunay-Weber syndrome is characterized by cutaneous hemangioma,
      arteriovenous fistulas or varicosities (or both), and unilateral hypertrophy of
      hard and soft tissues with different localization. Klippel-Trenaunay-Weber
      syndrome represents a syndrome of interest for those in the fields of oral and
      maxillofacial radiology and pathology because of the high incidence of compromise
      of the orofacial area in affected patients. The patient reported here presents
      with all of the 3 characteristic signs of the syndrome. The somatic and facial
      hypertrophy is contralateral to angiomata. As revealed through the use of
      magnetic resonance imaging, the primary component of facial hypertrophy is adipic
      subcutaneous tissue. Statistical analysis of the dental dimensions revealed that
      teeth on the hypertrophic side are significantly larger than normal.

PMID- 14716273
TI  - Arthroscopic rotator cuff repair: 4- to 10-year results.
AB  - PURPOSE: The purpose of this article is to report the 4- to 10-year results of
      arthroscopic repair of full- thickness rotator cuff tears. TYPE OF STUDY: This is
      a retrospective study evaluating a series of arthroscopic rotator cuff repairs
      performed by a single surgeon from February 1990 to February 1996. METHODS:
      Retrospective chart reviews and telephone interviews were performed to evaluate
      the results of arthroscopic repair of rotator cuff tears. Results were evaluated
      using a modified University of California, Los Angeles (UCLA), shoulder scoring
      system. RESULTS: One-hundred five arthroscopic rotator cuff repairs were
      performed in 104 patients between February 1990 and February 1996. Of these, 95
      patients (96 shoulders) were available for follow-up evaluation at the time of
      this review. The mean UCLA score of all shoulders involved was 32. Fifty-one
      patients showed excellent results; 39, good; 2, fair; and 4, poor according to
      the modified UCLA scoring system. In no case was any loss of motion noted as a
      result of the surgical intervention. CONCLUSIONS: This retrospective study is the
      largest series of arthroscopic rotator cuff repairs with the longest period of
      follow-up thus far reported. Of the patients available for follow-up evaluation,
      94% of patients qualified as a good to excellent result according to the UCLA
      shoulder scoring system. This study shows that patients treated with this
      arthroscopic rotator cuff repair technique have maintained excellent clinical
      outcomes 4 to 10 years after surgery. LEVEL OF EVIDENCE: Level IV.

PMID- 14716274
TI  - Arthroscopic repair of large rotator cuff tears using the interval slide
      technique.
AB  - PURPOSE: In some cases of larger and chronic rotator cuff tears, the
      supraspinatus tendon may be held in a retracted position by the contracted tissue
      of the rotator interval and the attached coracohumeral ligament. This study was
      performed to evaluate the utility and clinical effectiveness of an arthroscopic
      release of the rotator interval from the supraspinatus tendon combined with
      repair of the rotator cuff. TYPE OF STUDY: Prospective clinical follow-up study.
      METHODS: Forty-three arthroscopic rotator cuff repairs were performed and
      followed up for an average of 32 months. All of these patients had large,
      contracted tears that could not be adequately mobilized without a rotator
      interval release. In each case, an arthroscopic rotator interval release and
      superior capsular release were performed to improve cuff mobility. End-to-bone
      and side-to-side repair was performed depending on the configuration of the tear.
      Postoperatively, the patients were evaluated using a modified University of
      California Los Angeles (UCLA) rating system. RESULTS: Forty-two repairs were
      available for at least 2-year follow-up. No cases of deltoid morbidity or
      progressive superior migration of the humeral head were seen. The average overall
      preoperative score was 17.4 (range, 9-26). The average postoperative score was
      36.4 (range, 20-45). We saw 21 excellent, 6 good, 11 fair, and 4 poor results
      based on prior criteria established for smaller tears. All of the average
      postoperative scoring categories were improved from preoperative scores. Only 3
      patients were not satisfied with their results. CONCLUSIONS: The use of the
      interval slide technique greatly improves supraspinatus mobility in the case of
      large retracted tears. Although average improvements were less than in our
      previous study of smaller tears, complete or partial repair of these tears yields
      good results and high patient satisfaction.

PMID- 14716275
TI  - Arthroscopic repair of massive, contracted, immobile rotator cuff tears using
      single and double interval slides: technique and preliminary results.
AB  - PURPOSE: The purpose of this study is to describe the technique and review the
      preliminary results of arthroscopic repair of massive, contracted, immobile
      rotator cuff tears using an interval slide technique. TYPE OF STUDY: Case series.
      METHODS: From January 1999 to December 2000, the senior author (S.S.B.) performed
      arthroscopic rotator cuff repair on 94 massive rotator cuff tears. Of these, 9
      (9.6%) were massive, severely contracted rotator cuff tears and required repair
      using an interval slide technique. A single interval slide was used in 6
      patients, and a double interval slide was used in 3 patients. All patients were
      evaluated preoperatively and postoperatively using a modified University of
      California Los Angeles (UCLA) scoring system. RESULTS: At a mean follow-up time
      of 17.9 months (range, 10-24 months), 8 of 9 patients were satisfied with the
      procedure. The mean UCLA score increased from 10.0 preoperatively to 28.3
      postoperatively (P <.00001). All patients showed some improvement in active
      motion, strength, or function. Active forward flexion improved significantly,
      from a preoperative mean of 108 degrees to a postoperative mean of 146.1 degrees
      (P =.025). Active external rotation increased significantly from a preoperative
      mean of 24.4 degrees to a postoperative mean of 35.0 degrees (P =.04). A
      significant increase in strength grade (2.2 to 3.6; P <.005) and function (2.5 to
      7.1; P <.0005) were also seen. We encountered no significant complications to the
      procedure. CONCLUSIONS: The interval slide technique provides a method of
      mobilization of massive, severely contracted, immobile rotator cuff tears
      allowing repair of previously irreparable tears. This technique, in conjunction
      with arthroscopic rotator cuff repair, may provide patients with improvements in
      pain, motion, strength, and overall shoulder function. LEVEL OF EVIDENCE: Level
      IV.

PMID- 14716276
TI  - Timeline of tibial tunnel expansion after single-incision hamstring anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to determine the time frame for tibial
      tunnel expansion in patients undergoing anterior cruciate ligament (ACL)
      reconstruction with hamstring autografts using an endoscopic technique. Does this
      expansion occur immediately after surgery or over the first 12 weeks of
      rehabilitation? TYPE OF STUDY: Observational study involving 10 patients.
      METHODS: The single incision technique used a transtibial approach for drilling
      the femoral tunnel. Femoral fixation was accomplished with a closed-loop
      EndoButton (Acufex, Smith & Nephew; Mansfield, MA) and tibial fixation with a
      soft tissue screw and washer augmented by a polylactic acid interference screw.
      Computed tomography (CT) scans were taken in a consistent manner at weeks 1 and
      12 after surgery to measure tibial and femoral tunnel expansion. RESULTS: The CT
      scans showed significant widening of the tibial tunnel between 1 and 12 weeks
      (mean area of tibial tunnel increased from 82.5 to 112.7 mm2; P =.001). Expansion
      of the femoral tunnel was also seen; however, this change was not statistically
      significant (P =.18). CONCLUSIONS: The expansion after surgery occurred over
      time, not immediately after surgery, and was probably caused by factors other
      than surgical technique. The significance of tibial tunnel expansion needs to be
      clinically correlated with a long-term study on the effect of tunnel expansion on
      graft survival.

PMID- 14716277
TI  - Popliteal cystoscopic excisional debridement and removal of capsular fold of
      valvular mechanism of large recurrent popliteal cyst.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of
      cystoscopic excisional debridement and removal of unilateral flow of the capsular
      fold of valvular mechanism in the posteromedial corner of the recurrent popliteal
      cyst. TYPE OF STUDY: Retrospective review. METHODS: From March 1998 to May 2000,
      we treated 14 cases of popliteal cyst by cystoscopic excisional debridement. The
      cysts were relatively large cysts, about 5 cm in diameter on sonography.
      Conservative treatment for about 1 year, with about 3 aspirations failed. The
      mean follow-up duration was 29.7 (24 to 36) months. We used Rauschning and
      Lindgren criteria for evaluations. We estimated surgical time. Patients underwent
      sonography 6 months and 1 year after surgery. Pain, range of motion, and
      recurrence were checked 1 year after surgery. RESULTS: The average surgical time
      was 45 (31 to 58) minutes. The time to pain elimination and full range of motion
      was 1 or 2 days after surgery. No recurrence was noted in any patients. At the
      last follow-up, patients reported no discomfort or pain, and all had free range
      of motion. Preoperatively, Rauschning and Lindgren criteria were grade 0 in 0
      cases; grade 1 in 3 cases; grade 2 in 10 cases; and grade 3 in 1 case. At 2 weeks
      after surgery, criteria were grade 0 in 13 cases and grade 1 in 1 case; at final
      follow-up evaluation, all were grade 0. Hematoma occurred in 1 case. However, in
      cases lost to follow-up and in short-term follow-up cases, technical errors
      occurred: not entering within the cyst in 2 cases, extravasion in 1 case, and
      recurrence in 1 case. CONCLUSIONS: A popliteal cystoscopic excisional debridement
      by motorized shaver and removal of the capsular fold of the valvular mechanism is
      an effective alternative to the open technique of treating popliteal cysts.

PMID- 14716278
TI  - Load to failure testing of new meniscal repair devices.
AB  - PURPOSE: New all-inside meniscal repair devices include those combining sutures
      with anchors and that allow for an "adjustable" repair. This study's purpose was
      to compare the failure strength of new meniscal repair devices with suture
      repairs. TYPE OF STUDY: Experimental laboratory biomechanical study. METHODS: A
      single repair was placed in a vertical longitudinal peripheral tear made in fresh
      adult porcine menisci. Group 1 had a vertically oriented suture using the FasT
      Fix (Smith & Nephew Endoscopy, Andover, MA) device. Group 2 had a horizontally
      oriented mattress suture using the FasT-Fix device. Group 3 had a repair using 2
      Arthrex (Naples, FL) meniscal darts. The Group 4 repair used a RapidLoc (Mitek
      Surgical Products, Westwood, MA) device. The Group 5 repair used the Arthrotek
      meniscal screw (Biomet, Warsaw, IN). Group 6 had a single vertical suture, and
      group 7 a single horizontal suture, both of 2-0 Mersilene (Ethicon, Somerville,
      NJ). Load to failure testing was performed. RESULTS: The vertical FasT-Fix suture
      had a mean load to failure of 70.9 N (1 SD +/- 33). The horizontal FasT-Fix
      suture had a mean load to failure of 72.1 N (+/- 23.5). The double Dart repair
      had a mean load to failure of 61.7 N (+/- 19). The RapidLoc repair had a mean
      load to failure of 43.28 N (+/- 3.98). The Arthrotek meniscal screw repair had a
      mean load to failure of 28.09 N (+/- 7.93). Failure occurred with device pullout
      of the inner rim (9 of 10) for the Darts, device pullout of the inner rim (6 of
      10) and pullout of the outer rim (4 of 10) for the Arthrotek screw, and suture
      breakage for the FasT-Fix and the RapidLoc devices. The vertical sutures' mean
      load to failure was 80.43 N (+/- 8.5), and all 13 failed by suture breaking. The
      horizontal sutures' mean failure load was 55.9 N (+/- 18.8), and failure was by
      both suture breaking (6 of 10) and pulling through the meniscal tissue (4 of 10).
      CONCLUSIONS: Some of the newer meniscal repair devices show improved loads to
      failure over earlier generations.

PMID- 14716279
TI  - Localization of the semitendinosus-gracilis tendon bifurcation point relative to
      the tibial tuberosity: an aid to hamstring tendon harvest.
AB  - PURPOSE: Autologous hamstring grafts are commonly used for knee reconstruction.
      The proximity of the saphenous nerve and its branches, the superficial medial
      collateral ligament, and the inherent variability of fascial attachments
      necessitates effective surgical incision placement to minimize tissue morbidity
      during graft harvest. This study describes a method of locating the
      semitendinosus and gracilis tendon bifurcation point relative to the tibial
      tuberosity. It uses a novel diagonal surgical incision placed between a proximal
      point placed 3 cm medial to the tibial tuberosity and at 3 cm distal and 5 cm
      medial to the tibial tuberosity. TYPE OF STUDY: Descriptive. METHODS: Thirty-one
      cadaveric knees (17 right, 14 left) were placed in a jig at 90 degrees flexion.
      Reference marks were placed over the tibial tuberosity, at 3 cm medial to the
      tibial tuberosity, and at 3 cm distal and 5 cm medial to the tibial tuberosity.
      An approximately 3.5-cm-long line (representing the incision) was drawn
      connecting the 2 points located medial to the tibial tuberosity. After incision,
      the semitendinosus and gracilis tendon bifurcation point locations were measured
      with an inflexible metric ruler (+/- 0.5 cm) and recorded. RESULTS: The mean
      bifurcation point was located 2.2 +/- 0.7 cm distal and 4.5 +/- 0.6 cm medial to
      the tibial tuberosity, directly on the proposed incision line. All bifurcation
      points were located within +/- 2 cm of the proposed incision. CONCLUSIONS: The
      traditionally used incision line is, on average, located 2 cm too lateral to the
      bifurcation point and in some cases may be located 3 to 4 cm too lateral, making
      tendon harvest more difficult and more likely to cause harvest-induced injury to
      adjacent tissues.

PMID- 14716280
TI  - The effect of normal saline irrigation at different temperatures on the surface
      of articular cartilage: an experimental study in the rat.
AB  - PURPOSE: To determine, with an electron microscope, the effects of irrigation
      fluid at different temperatures on the surface of articular cartilage. TYPE OD
      STUDY: Experimental in vivo study. METHODS: With a scanning electron microscope,
      we investigated the effect of 2 hours of irrigation with normal saline at 3
      different temperatures (4 degrees C, 25 degrees C, and 37 degrees C) on articular
      hyaline cartilage in an in vivo rat knee model study. The contralateral knees
      were used as controls. We then compared the results. RESULTS: Specimens irrigated
      with cold (4 degrees C) fluid seemed to show the most uneven surface and apparent
      fibril exposure. Those irrigated with fluid close to body temperature (37 degrees
      C) showed the most even surface without fibril exposure. CONCLUSIONS: Although
      further work is needed to evaluate the long-term effects, using warm irrigation
      fluid to maintain the intra-articular environment at a more physiologically
      normal temperature may help reduce damage to cartilage during irrigation.

PMID- 14716281
TI  - Cyclic testing of arthroscopic knot security.
AB  - PURPOSE: Arthroscopic soft tissue repairs undergo many cycles of tensioning and
      relaxation before significant tissue healing occurs, and knot security under
      cyclic loads is essential for good results after these repairs. The current study
      was designed to assess the security of arthroscopic knots under stepwise cyclic
      loading. TYPE OF STUDY: In vitro materials testing. METHODS: Three types of
      arthroscopic knots--sliding knots with loop reversal but without post switching
      (S=SxSxSxS), modified Revo knots with loop reversal and post switching twice
      (S=S//xSxS//xS), and the SMC knot backed by 2 throws with loop reversal and post
      switching (S//xS//xS)--were compared with five-throw square knots tied with an
      open technique. All knots were tied with No. 2 braided nonabsorbable suture
      around 2 aluminum rods. They were pretensioned to 10 N, and initial displacement
      was recorded. The knots were then cycled at 1 Hz for 9 different load levels,
      with 250 cycles at each level, followed by a 30-second rest period to allow
      recording of permanent laxity of the suture loop. The first step of cyclic
      loading was from 10 to 40 N, and the upper limit was increased by 10 N for each
      successive load level. Any knot surviving cyclical loading was pulled to failure.
      RESULTS: Ten knots of each configuration were tested. All 3 arthroscopic slip
      knots showed significantly less initial displacement compared with the square
      knots (0.26 mm compared with 0.45 mm, respectively, P <.005). All square and
      modified Revo knots reached the ninth (120 N) loading level, whereas only 6 of
      the SMC knots and 3 of the arthroscopic knots without post switching reached the
      ninth loading level. Furthermore, all square and modified Revo knots failed by
      suture breakage at the knot, whereas 8 arthroscopic knots without post switching
      and 5 SMC knots failed by slipping. In fact, 3 of the arthroscopic knots without
      post switching and 1 of the SMC knots failed during the initial cyclic loading
      from 10 to 40 N. The modified Revo knots reached 3 mm of permanent laxity at
      significantly higher load levels than the square knots tied with an open
      technique (96 N v 78 N, P <.005). The SMC knots reached 3 mm of permanent laxity
      at statistically similar load levels compared with the square knots, but showed
      considerably more variability. None of the arthroscopic knots without post
      switching survived the entire cyclic-loading protocol. Four square, 5 modified
      Revo, and 5 SMC knots that survived cyclic loading reached ultimate failure at
      statistically similar load levels (157, 156, and 152 N, respectively).
      CONCLUSIONS: Post switching and loop reversal are key to arthroscopic knot
      security. Arthroscopic slip knots may be tighter at the time of knot construction
      than openly hand-tied square knots. The modified Revo knots appear to be as
      durable as openly hand-tied square knots regarding resistance to loosening under
      cyclic loading conditions. Security of arthroscopic knots without post switching
      is quite variable, making these knots less reliable. The SMC knot also proved not
      to be as reliable as the square and modified Revo knots when cyclically tested.

PMID- 14716282
TI  - Arthroscopic treatment of a ganglion of the first metatarsophalangeal joint.
AB  - The case of a ganglion that had developed around the first metatarsophalangeal
      (MTP) joint and in which several other therapeutic approaches were unsuccessful
      was treated using an arthroscopic assisted procedure. During MTP arthroscopy, we
      found that the pedicle of the tumor was attached to the interior of the joint,
      and the lesion was successfully extirpated. Communication with the cyst was found
      on the medial side of the lateral sesamoid bone, which coincided with the rounded
      portion of the first MTP joint at the sole, where stress is exerted repeatedly
      while walking. Thus, the intracystic fluid could not return to the intra
      articular space. Instead the cyst gradually extended to the extra-articular
      tissue, where it was relatively loosely connected. Researchers suspect that a
      ganglion originally develops through repeated mechanical stress; the lesion is
      constantly under pressure because of the weight bearing on it. Because of a
      higher pressure within the MTP joint, the communicating opening acts as a valve.

PMID- 14716283
TI  - Retrograde cartilage transplantation on the proximal and distal tibia.
AB  - The authors, with experience with more than 400 osteochondral autograft
      transplantation (OATS) cases since 1996, report a new technique of a retrograde
      osteochondral autograft transplantation for the treatment of isolated
      osteochondral lesions of the proximal and the distal tibia started in 1999. We
      treated 5 patients, 3 who presented with painful traumatic chondral defects in
      the central weight-bearing portion of the tibial plateau (1 in the medial and 2
      in the lateral compartment), and 2 who presented with painful chondral lesions on
      the distal tibia. An anterior cruciate ligament (ACL) drill guide positioned in
      the center of the defect was used to accurately prepare the cartilage surface, in
      one case arthroscopically and in 4 cases through an open incision. A guide-wire
      was introduced and drilled through the tibia, and a cannulated reamer equal to
      the diameter of the defect was advanced. An osteochondral cylinder was harvested
      from the non-weight-bearing zone of the femoral trochlea at the angle that
      corresponded to the angle on the ACL drill guide. The autograft was inserted in a
      retrograde fashion from the cortical window into the tibial tunnel to be flush
      with the articular surface in press-fit technique. The remaining tunnel defect
      between the cortical window on the tibia and the distal aspect of the autograft
      was filled with a cancellous bony cylinder and secured with a diagonal
      bioabsorbable screw. A concomitant varus deformity with the lesion on the medial
      tibial plateau was corrected in the same surgery using a high tibial osteotomy to
      relieve stress on the graft. Patients were followed up for 6 to 35 months. A
      complete healing of the grafts was seen in control magnetic resonance images
      (MRIs). All patients were satisfied with the surgery. Control arthroscopies
      showed the osteochondral cylinders well integrated and flush with the articular
      surface.

PMID- 14716284
TI  - Arthroscopic autologous chondrocyte implantation for the treatment of a chondral
      defect in the tibial plateau of the knee.
AB  - The matrix-induced autologous chondrocyte implantation (MACI; Verigen,
      Leverkusen, Germany) is a tissue engineering technique for the treatment of deep
      chondral lesions. Cultured chondrocytes are seeded on a collagen membrane that
      can be implanted into the defect using exclusively fibrin glue. These features
      imply some surgical advantages with respect to the traditional ACI technique,
      such as the possibility of performing the procedure in articular sites, in which
      putting stitches for the periosteal patch is impossible. We report on the
      arthroscopic MACI technique for the treatment of a chondral defect of the knee. A
      25-year-old man suffered persistent pain at the left knee after a violent direct
      trauma. Magnetic resonance imaging (MRI) and arthroscopic examination at the time
      of cartilage biopsy revealed a 2-cm2 chondral lesion in the posterior portion of
      the lateral tibial plateau. The implantation procedure was performed through
      traditional arthroscopic portals, and the seeded membrane was fixed with fibrin
      glue, excluding water flow temporarily. Implant stability was verified
      intraoperatively, and filling of the defect was shown 12 months after surgery by
      MRI, which showed a hyaline-like cartilage signal. In this specific case, the
      arthroscopic approach allowed to achieve an optimal view of the lesion, without
      sacrificing any tendinous or ligamentous structure of the knee.

PMID- 14716285
TI  - Arthroscopic biceps tenodesis using a bioabsorbable interference screw.
AB  - Arthroscopic biceps tenodesis has rarely been reported. The purpose of this study
      is to present our technique of arthroscopic biceps tenodesis using the Bio
      Tenodesis (Arthrex, Naples, FL) screw system. This system uses a uniquely
      designed screwdriver that allows manipulation of the biceps tendon subacromially
      and intra-articularly, facilitates placement and maintenance of the biceps tendon
      at the base of the bone socket during interference screw insertion, and assures
      an adequate bone-tendon-screw interface.

PMID- 14716286
TI  - An easy and effective method for reattaching an anterior cruciate ligament
      avulsion fracture from the tibial eminence.
AB  - Numerous ways to attach an anterior cruciate ligament avulsion from tibial
      eminence have been devised, and this report is the first of its kind to describe
      an easy but effective way of passing nonabsorbable braided sutures through the
      substance of the anterior cruciate ligament and hold down the avulsed bone
      fragments by tying knots over a bone bridge.

PMID- 14716287
TI  - All-inside suture technique using two posteromedial portals in a medial meniscus
      posterior horn tear.
AB  - Up to two thirds of patients with anterior cruciate ligament rupture have a
      combined medial meniscus posterior horn tear. Researchers have proven the
      importance of repairing this tear to enhance stability after anterior cruciate
      ligament reconstruction. However, repairing the meniscal tear can be sometimes
      cumbersome and difficult or even impossible in certain circumstances, especially
      in places such as the posterior horn of the medial meniscus. We devised a simple
      and easy method of all-inside suturing of medial meniscus posterior horn tears
      using a 2-posteromedial portal system. Furthermore, with a modification of our
      technique, a clinician can not only suture single but also double longitudinal
      medial meniscus posterior horn tears.

PMID- 14716288
TI  - Meniscal cyst formation after inside-out meniscal repair.
AB  - Complications after meniscal repair have been associated with inside-out and
      outside-in techniques. After the introduction of devices for meniscal repair,
      reports of chondral damage have been increasing. However, meniscal cyst formation
      after use of suture materials for meniscal repair is a very rare complication. We
      report a case of meniscal cyst formation after use of nonabsorbable sutures for
      meniscal repair.

PMID- 14716289
TI  - Pseudoaneurysm of the popliteal artery after anterior cruciate ligament
      reconstruction with bicortical tibial screw fixation.
AB  - We present a case report of a pseudoaneurysm of the popliteal artery after
      anterior cruciate ligament reconstruction using a bicortical tibial screw
      fixation 12 days after surgery. Surgical exploration and repair of an intimal
      lesion of the popliteal artery was performed. At 4-months' follow-up, there was
      still sensory loss in areas of the saphenous, medial plantar, calcaneal, and
      superficial peroneal nerves.

PMID- 14716290
TI  - Late cytomegalovirus polyradiculopathy following haploidentical CD34+-selected
      hematopoietic stem cell transplantation.
AB  - A 55-year-old man with acute myeloid leukemia in second relapse presented 4
      months after haploidentical CD34+-selected hematopoietic stem cell
      transplantation (HSCT) with symmetric, progressive neurological deficits of the
      lower extremities. Although there was no molecular evidence for drug resistance
      in the cerebral-spinal fluid, antiviral combination therapy failed to control the
      rapidly progressing CMV polyradiculopathy (PRP) and encephalitis, which were
      confirmed by autopsy studies. Late CMV PRP as an unusual manifestation of CMV
      disease should be kept in mind in patients with suggestive neurological symptoms
      after HSCT.

PMID- 14716291
TI  - Secondary Philadelphia chromosome after non-myeloablative peripheral blood stem
      cell transplantation for a myelodysplastic syndrome in transformation.

PMID- 14716292
TI  - The shortest telomeres drive karyotype evolution in transformed cells.
AB  - Maintenance of telomeres is essential for chromosome stability. In the absence of
      telomerase, telomeres shorten with cell division until they approach a stability
      threshold, at which point cells enter senescence. When senescence-signaling
      pathways are inactive, further telomere shortening leads to chromosome
      instability characterized by telomeric fusions and breakage-fusion-bridge (BFB)
      cycles. Since the distribution of telomere lengths among chromosome extremities
      is heterogeneous, we wondered about the impact of such variability on the
      stability of particular chromosome arms. We correlated the initial length of
      individual telomeres in telomerase-negative-transformed cells with the stability
      of the corresponding chromosome arms during the precrisis period. We show that
      arms carrying the shortest telomeres are the first to become unstable and this
      instability affects the chromosome homologues with shorter telomeres almost
      exclusively. The analysis of several postcrisis cell populations, which had
      stabilized their telomeres by re-expressing telomerase, showed that the
      karyotypic outcome is strongly influenced by the initial telomere length
      heterogeneity. The timing of telomerase re-expression also seems to play a role
      in limiting the extent of karyotypic changes, probably by reducing the frequency
      of telomeric fusions and hence BFB. Since the distribution of telomere lengths
      within somatic cells is proper to every individual, our results predict that the
      risk for a particular chromosome arm of becoming unstable early in tumorigenesis
      will differ between individuals and contribute directly to the heterogeneity of
      chromosome aberrations found in tumors.

PMID- 14716293
TI  - IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell
      survival, and enhances their susceptibility to apoptosis and cancer drugs.
AB  - We identified seven putative splice variants of the human IG20 gene. Four
      variants namely, IG20, MADD, IG20-SV2 and DENN-SV are expressed in human tissues.
      While DENN-SV is constitutively expressed in all tissues, expression of IG20
      appears to be regulated. Interestingly, overexpression of DENN-SV enhanced cell
      replication and resistance to treatments with TNFalpha, vinblastine, etoposide
      and gamma-radiation. In contrast, IG20 expression suppressed cell replication and
      increased susceptibility to the above treatments. Moreover, cells that were
      resistant and susceptible to TNFalpha-induced apoptosis exclusively expressed
      endogenous DENN-SV and IG20, respectively. When PA-1 ovarian cancer cells that
      are devoid of endogenous IG20 variant, but express higher levels of DENN-SV, were
      transfected with IG20, they showed reduced cell proliferation and increased
      susceptibility to apoptosis induced by TNFalpha, TRAIL and gamma-radiation. This
      indicated that overexpression of IG20 can override endogenous DENN-SV function.
      CrmA reversed the effects of IG20, but not DENN-SV. In contrast, dominant
      negative-I-kappa B reversed the effects of DENN-SV, but not IG20, and showed that
      DENN-SV most likely exerted its effects through NFkappaB activation. Together,
      our data show that IG20 gene can play a novel and significant role in regulating
      cell proliferation, survival and death through alternative mRNA splicing.

PMID- 14716294
TI  - Autorepression of c-myc requires both initiator and E2F-binding site elements and
      cooperation with the p107 gene product.
AB  - Myc proteins are transcriptional activators, but also repress transcription
      through initiator (Inr) elements. Repression requires the conserved Myc Box II,
      but the cis-acting element(s) required for c-myc autorepression have eluded
      definition. Since the gene has a candidate Inr at the P2 promoter, we tested
      whether Myc autorepression operates through the Inr/BoxII mechanism.
      Overexpression of c-Myc but not a Box II deletion mutation represses both c-myc
      P2 reporter genes and endogenous c-myc, as does Mxi1 expression. Only 45
      nucleotides surrounding the P2 start suffice to mediate autorepression, but Myc
      and Mxi1 also downregulate P2 Inr mutations, suggesting other core promoter
      sequence requirements for autorepression. We tested the importance of conserved
      E2F sites, based on known Myc interaction with the pRb-related p107 and on the
      transrepressive effects of Rb family proteins. Myc, Mxi1, and p107 repress c-myc
      somewhat less well in the absence of E2F binding sites, while an E2F+Inr double
      mutation is not repressed at all by these gene products. Further, Myc repression
      at the c-myc P2 core promoter is augmented by p107, but not by pRb or p130, nor
      by p107 lacking the conserved pocket domain. Our data suggest that Myc
      autorepression requires both the c-myc Inr and E2F sites in cis, as well as p107
      in trans. Consistent with this, we found that retrovirally transduced c-Myc
      cannot downregulate endogenous c-myc in p107-null fibroblasts, and show evidence
      that both Myc and p107 are present in a complex assembled at the c-myc P2 core
      promoter.

PMID- 14716295
TI  - The EBNA-3 gene family proteins disrupt the G2/M checkpoint.
AB  - The Epstein-Barr nuclear antigens (EBNA), EBNA-3, -4 and -6, have previously been
      shown to act as transcriptional regulators, however, this study identifies
      another function for these proteins, disruption of the G2/M checkpoint.
      Lymphoblastoid cell lines (LCLs) treated with a G2/M initiating drug azelaic
      bishydroxamine (ABHA) did not show a G2/M checkpoint response, but rather they
      display an increase in cell death, a characteristic of sensitivity to the
      cytotoxic effects of the drug. Cell cycle analysis demonstrated that the
      individual expression of EBNA-3, -4 or -6 are capable of disrupting the G2/M
      checkpoint response induced by ABHA resulting in increased toxicity, whereas EBNA
      2, and -5 were not. EBNA-3 gene family protein expression also disrupted the G2/M
      checkpoint initiated in response to the genotoxin etoposide and the S phase
      inhibitor hydroxyurea. The G2 arrest in response to these drugs were sensitive to
      caffeine, suggesting that ATM/ATR signalling in these checkpoint responses may be
      blocked by the EBNA-3 family proteins. The function of EBNA-3, -4 and -6 proteins
      appears to be more complex than anticipated and these data suggest a role for
      these proteins in disrupting the host cell cycle machinery.

PMID- 14716296
TI  - Identification of maspin and S100P as novel hypomethylation targets in pancreatic
      cancer using global gene expression profiling.
AB  - DNA hypomethylation is one of the major epigenetic alterations in human cancers.
      We have previously shown that genes identified as hypomethylated in pancreatic
      cancer are expressed in pancreatic cancer cell lines, but not in normal
      pancreatic ductal epithelium and can be reexpressed in nonexpressing cells using
      'epigenetic modifying agents' such as DNA methyltransferase inhibitors. To
      identify additional targets for aberrant hypomethylation in pancreatic cancer, we
      used oligonucleotide microarrays to screen for genes that displayed expression
      patterns associated with hypomethylation. This analysis identified a substantial
      number of candidates including previously reported hypomethylated genes. A subset
      of eight genes were selected for further methylation analysis, and two cancer
      related genes, maspin and S100P, were found to be aberrantly hypomethylated in a
      large fraction of pancreatic cancer cell lines and primary pancreatic carcinomas.
      Combined treatment with 5-aza-2'-deoxycytidie and trichostatin A resulted in
      synergistic induction of maspin and S100P mRNA in MiaPaCa2 cells where both genes
      were methylated. Furthermore, there was an inverse correlation between
      methylation and mRNA expression level for maspin and S100P in a large panel of
      pancreatic cancer cell lines. We also found a significant difference in the
      methylation patterns of maspin and two previously identified hypomethylated genes
      (trefoil factor 2 and lipocalin 2) between pancreatic and breast cancer cell
      lines, suggesting cancer-type specificity for some hypomethylation patterns.
      Thus, our present results confirm that DNA hypomethylation is a frequent
      epigenetic event in pancreatic cancer, and suggest that gene expression profiling
      may help to identify potential targets affected by this epigenetic alteration.

PMID- 14716297
TI  - A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer.
AB  - We report here that HtrA1, a candidate tumor suppressor, is downregulated in
      ovarian cancer. Expression of HtrA1 is downregulated in five of seven ovarian
      cancer cell lines. In total, 59% of primary ovarian tumors have either a complete
      absence or markedly reduced levels of HtrA1 expression compared to the brushings
      of ovarian surface epithelium. Primary ovarian tumors show high frequencies of
      loss of an allele at microsatellite markers near htrA1 locus on 10q26.
      Downregulation of HtrA1 in SKOV3 by antisense transfection promotes anchorage
      independent growth, while exogenous expression of HtrA1 in OV202 induces cell
      death. HtrA1-induced cell death is not inhibited by the broad caspase inhibitor,
      zVAD(OMe)fmk, but instead reflects serine protease activity associated with
      HtrA1. These observations raise the possibility of HtrA1 as a candidate tumor
      suppressor involved in promoting serine-protease-mediated cell death and that
      downregulation of HtrA1 in ovarian cancer may contribute to malignant phenotype.

PMID- 14716298
TI  - Amplification and overexpression of E2F3 in human bladder cancer.
AB  - We demonstrate that, in human bladder cancer, amplification of the E2F3 gene,
      located at 6p22, is associated with overexpression of its encoded mRNA
      transcripts and high levels of expression of E2F3 protein. Immunohistochemical
      analyses of E2F3 protein levels have established that around one-third (33/101)
      of primary transitional cell carcinomas of the bladder overexpress nuclear E2F3
      protein, with the proportion of tumours containing overexpressed nuclear E2F3
      increasing with tumour stage and grade. When considered together with the
      established role of E2F3 in cell cycle progression, these results suggest that
      the E2F3 gene represents a candidate bladder cancer oncogene that is activated by
      DNA amplification and overexpression.

PMID- 14716299
TI  - AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis.
AB  - Cyclophilin A (CypA) was determined to interact with apoptosis-inducing factor
      (AIF) by mass spectroscopy, coimmunoprecipitation, pull-down assays, and
      molecular modeling. During the initial, caspase-independent stage of chromatin
      condensation that accompanies apoptosis, AIF and CypA were found to
      coimmunolocalize in the nucleus. Recombinant AIF and CypA proteins synergized in
      vitro in the degradation of plasmid DNA, as well as in the capacity to induce DNA
      loss in purified nuclei. The apoptogenic cooperation between AIF and CypA did not
      rely on the CypA peptidyl-prolyl cis-trans isomerase activity. In Cyp-expressing
      cells, AIF overexpression augmented apoptotic chromatinolysis. The AIF-dependent
      large-scale DNA fragmentation was less pronounced in CypA knockout cells as
      compared to controls. AIF mutants lacking the CypA-binding domain were
      inefficient apoptosis sensitizers in transfection experiments. Moreover, AIF
      failed to sensitize CypA knockout cells to apoptosis induction, and this defect
      in the AIF response was reversed by reintroduction of the CypA gene into CypA
      deficient cells. In summary, AIF and CypA collaborate in chromatinolysis.

PMID- 14716300
TI  - Apoptosis signaling triggered by the marine alkaloid ascididemin is routed via
      caspase-2 and JNK to mitochondria.
AB  - The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even
      against multidrug-resistant cancer cells. Here, we address the signaling pathways
      utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC
      (0.5-20 microM) induces a mitochondrial pathway that requires the activation of
      the initiator caspase-2 upstream of mitochondria. ASC-triggered apoptosis
      occurred independent of CD95, but required mitochondrial dysfunction. The
      activation of caspase-2 was shown to precede the processing of caspase-8, -9 and 
      3. The specific caspase-2 inhibitor zVDVADfmk abrogated ASC-induced DNA
      fragmentation almost completely. Overexpression of Bcl-x(L) blocked caspase-8 but
      not caspase-2 processing. Conversely, caspase-2 inhibition strongly reduced
      caspase-9 activation. As a possible link between caspase-2 and mitochondrial
      dysfunction, Bid was found to be cleaved by ASC. In addition, JNK was activated
      by ASC upstream of mitochondria via reactive oxygen species. The specific JNK
      inhibitor SP600125 partially inhibited caspase-2 and -9 processing as well as
      cytochrome c release and DNA fragmentation indicating that JNK contributes to,
      but is not necessary for ASC-mediated apoptosis. Thus, ASC triggers a pathway in
      which early activation of caspase-2 provides a possible link between its DNA
      damaging activity and the induction of mitochondrial dysfunction. The activation
      of JNK contributes to this signaling upstream of mitochondria.

PMID- 14716301
TI  - Loss of CCAAT/enhancer binding protein delta promotes chromosomal instability.
AB  - The transcription factor CCAAT/enhancer binding protein delta (Cebpd, also known
      as C/EBPdelta, CRP3, CELF, NF-IL6beta) is implicated in diverse cellular
      functions such as the acute phase response, adipocyte differentiation, learning
      and memory, and mammary epithelial cell growth control. Here, we report that lack
      of Cebpd causes genomic instability and centrosome amplifications in primary
      embryonic fibroblasts derived from 129S1 mice. Upon spontaneous immortalization,
      Cebpd-deficient fibroblasts acquire transformed features such as impaired contact
      inhibition and reduced serum dependence. These data identify a novel role for
      Cebpd in the maintenance of chromosomal stability and suggest a potential tumor
      suppressor function in vivo.

PMID- 14716303
TI  - Shape and stability of self-assembled surface domains.
AB  - The shapes of two-dimensional (2D) nanostructures on surfaces are determined by
      their boundary energies as well as by long-range elastic, electrostatic or
      magnetic interactions. Although it is well known that long-range interactions can
      give rise to shape bifurcation-an abrupt change in shape symmetry at a critical
      size-a general description of the evolution of shape with size, systematically
      incorporating both the azimuthal dependence of the boundary energy and long-range
      interactions, has been lacking. Here we show that unconstrained shape relaxation,
      including previously ignored boundary curvature, leads to a novel, continuous
      shape change from convex at small size to concave at large size. In addition to
      demonstrating a method to quantitatively determine the azimuthal dependence of
      the boundary energy, we show that the energy gain associated with boundary
      curvature relaxation is a key factor in stabilizing surface nanostructures. For 7
      x 7 domains on Si(111), boundary curvature reduces the formation free-energy by
      up to 50%.

PMID- 14716302
TI  - Epstein-Barr virus latent membrane protein 1 induces micronucleus formation,
      represses DNA repair and enhances sensitivity to DNA-damaging agents in human
      epithelial cells.
AB  - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a viral
      oncogene and it is essential for the transformation of resting B cells by the
      virus. The protein acts as a ligand-less membrane receptor and triggers numerous
      cellular signaling pathways. Cellular transformation frequently has been
      associated with genomic instability. To investigate whether EBV LMP1 induces
      chromosomal aberrations, micronucleus (MN) formation was examined in LMP1
      expressing epithelial cells. The expression of wild-type LMP1 enhanced both
      spontaneous and bleomycin-induced MN formation. MN formation may be induced by
      inactivation of DNA repair and, therefore, we investigated the effect of LMP1 on
      DNA repair, using a host cell reactivation (HCR) assay. In the HCR assay, LMP1
      reduced the capacity for DNA repair of both NPC-TW01 (p53-wild-type) and H1299
      (p53-deficient) cells. As reduction of DNA repair by LMP1 occurs in p53-wild-type
      and p53-deficient cells, it seems that LMP1 can repress DNA repair in a p53
      independent manner. Inactivation of DNA repair may render cells sensitive to DNA
      damaging agents. In this study, H1299 cells harboring LMP1 were shown to be more
      sensitive to UV and bleomycin than those with a vector control. Using various
      deletion mutants of EBV LMP1 to determine the regions of LMP1 required to enhance
      MN formation, inhibit DNA repair and sensitize cells to DNA-damaging agents, we
      found that the region a. a. 189-222 (located within the CTAR1 domain) was
      responsible for sensitizing cells to UV and bleomycin, as well as for enhancing
      MN formation and repressing DNA repair. Based on these results, we suggest that
      disruption of DNA repair by LMP-1 results in an accumulation of unrepaired DNA
      and consequent genomic instability, which may contribute to the oncogenesis of
      LMP1 in human epithelial cells.

PMID- 14716304
TI  - Large electric-field-induced strain in ferroelectric crystals by point-defect
      mediated reversible domain switching.
AB  - Ferroelectric crystals are characterized by their asymmetric or polar structures.
      In an electric field, ions undergo asymmetric displacement and result in a small
      change in crystal dimension, which is proportional to the applied field. Such
      electric-field-induced strain (or piezoelectricity) has found extensive
      applications in actuators and sensors. However, the effect is generally very
      small and thus limits its usefulness. Here I show that with a different
      mechanism, an aged BaTiO(3) single crystal can generate a large recoverable
      nonlinear strain of 0.75% at a low field of 200 V mm(-1). At the same field this
      value is about 40 times higher than piezoelectric Pb(Zr, Ti)O(3) (PZT) ceramics
      and more than 10 times higher than the high-strain Pb(Zn(1/3)Nb(2/3))O(3)
      PbTiO(3) (PZN-PT) single crystals. This large electro-strain stems from an
      unusual reversible domain switching (most importantly the switching of non-180
      degrees domains) in which the restoring force is provided by a general symmetry
      conforming property of point defects. This mechanism provides a general method to
      achieve large electro-strain effect in a wide range of ferroelectric systems and
      the effect may lead to novel applications in ultra-large stroke and nonlinear
      actuators.

PMID- 14716305
TI  - Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate
      metabolism in vivo.
AB  - The transcription factor, signal transducer and activator of transcription-3
      (STAT-3) contributes to various physiological processes. Here we show that mice
      with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system,
      show insulin resistance associated with increased hepatic expression of
      gluconeogenic genes. Restoration of hepatic STAT-3 expression in these mice,
      using adenovirus-mediated gene transfer, corrected the metabolic abnormalities
      and the alterations in hepatic expression of gluconeogenic genes. Overexpression
      of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression
      independently of peroxisome proliferator-activated receptor-gamma coactivator-1
      alpha (PGC-1 alpha), an upstream regulator of gluconeogenic genes. Liver-specific
      expression of a constitutively active form of STAT-3, achieved by infection with
      an adenovirus vector, markedly reduced blood glucose, plasma insulin
      concentrations and hepatic gluconeogenic gene expression in diabetic mice.
      Hepatic STAT-3 signaling is thus essential for normal glucose homeostasis and may
      provide new therapeutic targets for diabetes mellitus.

PMID- 14716306
TI  - Two-photon fluorescence correlation microscopy reveals the two-phase nature of
      transport in tumors.
AB  - Transport parameters determine the access of drugs to tumors. However, technical
      difficulties preclude the measurement of these parameters deep inside living
      tissues. To this end, we adapted and further optimized two-photon fluorescence
      correlation microscopy (TPFCM) for in vivo measurement of transport parameters in
      tumors. TPFCM extends the detectable range of diffusion coefficients in tumors by
      one order of magnitude, and reveals both a fast and a slow component of
      diffusion. The ratio of these two components depends on molecular size and can be
      altered in vivo with hyaluronidase and collagenase. These studies indicate that
      TPFCM is a promising tool to dissect the barriers to drug delivery in tumors.

PMID- 14716307
TI  - A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma.
AB  - Mucus hypersecretion is a crucial feature of pulmonary diseases such as asthma,
      chronic bronchitis and cystic fibrosis. Despite much research, there is still no
      effective therapy for this condition. Recently, we showed that the myristoylated,
      alanine-rich C-kinase substrate (MARCKS) protein is required for mucus secretion
      by human bronchial epithelial cells in culture. Having synthesized a peptide
      corresponding to the N-terminal domain of MARCKS, we now show that the
      intratracheal instillation of this peptide blocks mucus hypersecretion in a mouse
      model of asthma. A missense peptide with the same amino acid composition has no
      effect. Based on quantitative histochemical analysis of the mouse airways, the
      peptide seems to act by blocking mucus release from goblet cells, possibly by
      inhibiting the attachment of MARCKS to membranes of intracellular mucin granules.
      These results support a pivotal role for MARCKS protein, specifically its N
      terminal region, in modulating this secretory process in mammalian airways.
      Intratracheal administration of this MARCKS-related peptide could therapeutically
      reduce mucus secretion in the airways of human patients with asthma, chronic
      bronchitis and cystic fibrosis.

PMID- 14716308
TI  - Therapeutic effects of lysophosphatidylcholine in experimental sepsis.
AB  - Sepsis represents a major cause of death in intensive care units. Here we show
      that administration of lysophosphatidylcholine (LPC), an endogenous
      lysophospholipid, protected mice against lethality after cecal ligation and
      puncture (CLP) or intraperitoneal injection of Escherichia coli. In vivo
      treatment with LPC markedly enhanced clearance of intraperitoneal bacteria and
      blocked CLP-induced deactivation of neutrophils. In vitro, LPC increased
      bactericidal activity of neutrophils, but not macrophages, by enhancing H(2)O(2)
      production in neutrophils that ingested E. coli. Incubation with an antibody to
      the LPC receptor, G2A, inhibited LPC-induced protection from CLP lethality and
      inhibited the effects of LPC in neutrophils. G2A-specific antibody also blocked
      the inhibitory effects of LPC on certain actions of lipopolysaccharides (LPS),
      including lethality and the release of tumor necrosis factor-alpha (TNF-alpha)
      from neutrophils. These results suggest that LPC can effectively prevent and
      treat sepsis and microbial infections.

PMID- 14716309
TI  - Identification of amino acid residues crucial for chemokine receptor
      dimerization.
AB  - Chemokines coordinate leukocyte trafficking by promoting oligomerization and
      signaling by G protein-coupled receptors; however, it is not known which amino
      acid residues of the receptors participate in this process. Bioinformatic
      analysis predicted that Ile52 in transmembrane region-1 (TM1) and Val150 in TM4
      of the chemokine receptor CCR5 are key residues in the interaction surface
      between CCR5 molecules. Mutation of these residues generated nonfunctional
      receptors that could not dimerize or trigger signaling. In vitro and in vivo
      studies in human cell lines and primary T cells showed that synthetic peptides
      containing these residues blocked responses induced by the CCR5 ligand CCL5.
      Fluorescence resonance energy transfer showed the presence of preformed, ligand
      stabilized chemokine receptor oligomers. This is the first description of the
      residues involved in chemokine receptor dimerization, and indicates a potential
      target for the modification of chemokine responses.

PMID- 14716310
TI  - TLR9 signals after translocating from the ER to CpG DNA in the lysosome.
AB  - Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll
      like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic
      reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no
      precedent for immune receptor signaling in the ER, we investigated how TLR9 is
      activated. We show that CpG DNA binds directly to TLR9 in ligand-binding studies.
      CpG DNA moves into early endosomes and is subsequently transported to a tubular
      lysosomal compartment. Concurrent with the movement of CpG DNA in cells, TLR9
      redistributes from the ER to CpG DNA-containing structures, which also accumulate
      MyD88. Our data indicate a previously unknown mechanism of cellular activation
      involving the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where
      signal transduction is initiated.

PMID- 14716311
TI  - Altered somatic hypermutation and reduced class-switch recombination in
      exonuclease 1-mutant mice.
AB  - The generation of protective antibodies requires somatic hypermutation (SHM) and
      class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice
      mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR),
      have decreased CSR and changes in the characteristics of SHM similar to those
      previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the
      first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1(-/-)
      mice and the finding that Exo1 and Mlh1 are physically associated with mutating
      variable regions support the idea that Exo1 and MMR participate directly in SHM
      and CSR.

PMID- 14716312
TI  - Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to
      T cells.
AB  - Members of the CD1 family present antigenic lipids to T lymphocytes. CD1
      molecules survey endocytic compartments for lipid antigens that are sorted into
      these vesicles after incorporation into the membrane bilayer, and extraction from
      the bilayer is likely to be a critical step for lipid association. We
      hypothesized that lysosomal saposins, which are cofactors required for
      sphingolipid degradation, might be involved in this process. Here we show that
      saposins, although not required for the autoreactive recognition of CD1d by
      natural killer T cells, are indispensable for the binding of an exogenous lipid
      antigen, alpha-galactosylceramide, to CD1d in the endocytic pathway. We suggest
      that saposins mobilize monomeric lipids from lysosomal membranes and facilitate
      their association with CD1d.

PMID- 14716313
TI  - Saposin C is required for lipid presentation by human CD1b.
AB  - Lipids from Mycobacterium tuberculosis are presented through CD1 proteins to T
      lymphocytes in humans, but the accessory molecules required for antigen loading
      and presentation remain unidentified. Here we show that fibroblasts deficient in
      sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate
      lipid-specific T cells. However, the T cell response was restored when
      fibroblasts were reconstituted with SAP-C but not other SAPs. Lipid antigen and
      SAP-C colocalized in lysosomal compartments, and liposome assays showed that SAP
      C efficiently extracts antigen from membranes. Coprecipitation demonstrated
      direct molecular interaction between SAP-C and CD1b. We propose a model in which
      SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b.
      Thus, SAP-C represents a missing link in antigen presentation of lipids through
      CD1b to human T cells.

PMID- 14716314
TI  - Repression of AGAMOUS-LIKE 24 is a crucial step in promoting flower development.
AB  - Flower development begins as floral meristems arise in succession on the flank of
      the inflorescence meristem. Floral meristem identity genes LEAFY (LFY) and
      APETALA1 (AP1) promote establishment and maintenance of floral identity in newly
      formed floral primordia. Without their activity, the floral primordia develop
      with inflorescence characteristics. The underlying molecular-genetic mechanism is
      unknown. Here we show that these phenotypes are due in large part to the ectopic
      expression of AGAMOUS-LIKE 24 (AGL24), a central regulator of floral meristem
      identity. We present evidence that AGL24 is an early target of transcriptional
      repression by LFY and AP1. Without such repression, continued AGL24 expression in
      floral meristems is sufficient to cause floral reversion regardless of the
      activation of floral organ identity genes. This indicates that LFY and AP1
      promote floral development not only by positively regulating genes activated in
      flower development, but also by repressing AGL24, a promoter of inflorescence
      fate.

PMID- 14716315
TI  - Sequencing of a rice centromere uncovers active genes.
AB  - Centromeres are the last frontiers of complex eukaryotic genomes, consisting of
      highly repetitive sequences that resist mapping, cloning and sequencing. The
      centromere of rice Chromosome 8 (Cen8) has an unusually low abundance of highly
      repetitive satellite DNA, which allowed us to determine its sequence. A region of
      approximately 750 kb in Cen8 binds rice CENH3, the centromere-specific H3
      histone. CENH3 binding is contained within a larger region that has abundant
      dimethylation of histone H3 at Lys9 (H3-Lys9), consistent with Cen8 being
      embedded in heterochromatin. Fourteen predicted and at least four active genes
      are interspersed in Cen8, along with CENH3 binding sites. The retrotransposons
      located in and outside of the CENH3 binding domain have similar ages and
      structural dynamics. These results suggest that Cen8 may represent an
      intermediate stage in the evolution of centromeres from genic regions, as in
      human neocentromeres, to fully mature centromeres that accumulate megabases of
      homogeneous satellite arrays.

PMID- 14716316
TI  - Enzyme immobilization in a biomimetic silica support.
AB  - Robust immobilization techniques that preserve the activity of biomolecules have
      many potential applications. Silicates, primarily in the form of sol-gel
      composites or functionalized mesoporous silica, have been used to encapsulate a
      wide variety of biomolecules but the harsh conditions required for chemical
      synthesis limit their applicability. Silaffin polypeptides from diatoms catalyze
      the formation of silica in vitro at neutral pH and ambient temperature and
      pressure. Here we show that butyrylcholinesterase entrapped during the
      precipitation of silica nanospheres retained all of its activity. Ninety percent
      of the soluble enzyme was immobilized, and the immobilized enzyme was
      substantially more stable than the free enzyme. The mechanical properties of
      silica nanospheres facilitated application in a flow-through reactor. The use of
      biosilica for enzyme immobilization combines the excellent support properties of
      a silica matrix with a benign immobilization method that retains enzyme activity.

PMID- 14716317
TI  - Antimicrobial drug discovery through bacteriophage genomics.
AB  - Over evolutionary time bacteriophages have developed unique proteins that arrest
      critical cellular processes to commit bacterial host metabolism to phage
      reproduction. Here, we apply this concept of phage-mediated bacterial growth
      inhibition to antibiotic discovery. We sequenced 26 Staphylococcus aureus phages
      and identified 31 novel polypeptide families that inhibited growth upon
      expression in S. aureus. The cellular targets for some of these polypeptides were
      identified and several were shown to be essential components of the host DNA
      replication and transcription machineries. The interaction between a prototypic
      pair, ORF104 of phage 77 and DnaI, the putative helicase loader of S. aureus, was
      then used to screen for small molecule inhibitors. Several compounds were
      subsequently found to inhibit both bacterial growth and DNA synthesis. Our
      results suggest that mimicking the growth-inhibitory effect of phage polypeptides
      by a chemical compound, coupled with the plethora of phages on earth, will yield
      new antibiotics to combat infectious diseases.

PMID- 14716318
TI  - The role of increasing temperature variability in European summer heatwaves.
AB  - Instrumental observations and reconstructions of global and hemispheric
      temperature evolution reveal a pronounced warming during the past approximately
      150 years. One expression of this warming is the observed increase in the
      occurrence of heatwaves. Conceptually this increase is understood as a shift of
      the statistical distribution towards warmer temperatures, while changes in the
      width of the distribution are often considered small. Here we show that this
      framework fails to explain the record-breaking central European summer
      temperatures in 2003, although it is consistent with observations from previous
      years. We find that an event like that of summer 2003 is statistically extremely
      unlikely, even when the observed warming is taken into account. We propose that a
      regime with an increased variability of temperatures (in addition to increases in
      mean temperature) may be able to account for summer 2003. To test this proposal,
      we simulate possible future European climate with a regional climate model in a
      scenario with increased atmospheric greenhouse-gas concentrations, and find that
      temperature variability increases by up to 100%, with maximum changes in central
      and eastern Europe.

PMID- 14716319
TI  - Strain-dependent inhibitory effect of mutant mi-MITF on cytotoxic activities of
      cultured mast cells and natural killer cells of mice.
AB  - MITF is a transcription factor encoded by the mi locus. MITF encoded by mi and
      Mi(or) mutant alleles (mi-MITF and Mi(or)-MITF, respectively) possessed an
      inhibitory effect, whereas the tg, mi(ew) and mi(ce) were null mutants. We
      examined the cytotoxic activities of cultured mast cells (CMCs) and natural
      killer (NK) cells of various MITF mutants in C57BL/6 (B6) background. Cytotoxic
      activities of CMCs and NK cells of B6-mi/mi and B6-Mi(or)/Mi(or) mice were
      remarkably reduced. In B6-tg/tg, B6-mi(ew)/mi(ew) and B6-mi(ce)/mi(ce) mice,
      however, the cytotoxic activity of CMCs was reduced only slightly and the NK
      activity was normal. The cytotoxic activity of CMCs paralleled with the
      expression level of granzyme B (Gr B) mRNA, and the NK activity with that of
      perforin (Pfn) mRNA. In contrast to the case of B6-mi/mi mice, cytotoxic
      activities of CMCs and NK cells were not impaired in WB-mi/mi mice. The
      expression of Gr B mRNA was not reduced in CMCs of WB-mi/mi mice, and that of Pfn
      mRNA was not reduced in NK cells of WB-mi/mi mice. WB-mi/mi mice appeared to have
      factor(s) compensating for the inhibitory effect of mi-MITF on the expression of
      Gr B and Pfn genes.

PMID- 14716320
TI  - Diabetic retinopathy progression and visual outcome after phacoemulsification in
      South-Asian and Afro-Caribbean patients with diabetes.
AB  - PURPOSE: To determine diabetic retinopathy or maculopathy progression and visual
      outcome following phacoemulsification in South-Asian and Afro-Caribbean patients
      with diabetes. METHODS: Review of notes of patients with type II diabetes
      undergoing phacoemulsification by one surgeon. The inclusion criteria were: (a)
      South-Asian or Afro-Caribbean ethnicity, (b) monocular cases with a minimum
      postoperative follow-up of 6 months, and (c) binocular cases with an interval of
      at least 6 months between the operation in the two eyes. The nonoperated eye was
      used as control. The development or progression of diabetic retinopathy or
      maculopathy and final visual acuity were recorded. RESULTS: In all, 30 diabetic
      patients were included. There were 19 South-Asians (Pakistani, Indian, and
      Bangladeshi) and 11 Afro-Caribbeans. The mean (+/-SD) age was 68.9 (+/-10) years.
      Retinopathy or maculopathy progression was noted in seven patients (23.4%), two
      South-Asians, and five Afro-Caribbeans. There was no significant difference in
      the number of operated and fellow eyes whose retinopathy or maculopathy
      progressed postoperatively. Progression of retinopathy or maculopathy occurred
      more often in Afro-Caribbeans compared to South-Asians (P=0.02, logistic
      regression analysis). The mean (+/-SD) postoperative follow-up was 12.4 (+/-6.5)
      months. Visual acuity improved by at least two or more Snellen lines in 19 eyes
      (63.3%); 26 eyes (86.7%) achieved a final visual acuity of at least 6/12.
      CONCLUSIONS: Afro-Caribbeans may be at a higher risk of progression of
      retinopathy or maculopathy after phacoemulsification.

PMID- 14716321
TI  - Retinal telangiectasia in association with macular hole formation.

PMID- 14716322
TI  - Early-stage diffuse unilateral subacute neuroretinitis: improvement of vision
      after photocoagulation of the worm.
AB  - PURPOSE: To evaluate the visual outcome after direct laser photocoagulation of
      the worm in patients with early-stage diffuse unilateral subacute neuroretinitis
      (DUSN). METHODS: We report on four patients with DUSN diagnosed in its early
      stage, in whom the worm was identified and destroyed by laser photocoagulation.
      RESULTS: In all the four cases, resolution of the inflammatory multifocal lesions
      was achieved within 1 month of treatment. After that period and during follow-up
      (mean 11.5 months), visual acuity improved in three eyes and remained unchanged
      in one eye. CONCLUSION: The diagnosis of DUSN in its early stage followed by
      prompt location and destruction of the worm by photocoagulation may improve
      vision of affected patients.

PMID- 14716323
TI  - Conjunctival molluscum contagiosum.

PMID- 14716324
TI  - Genetic polymorphism of hOGG1 and risk of pterygium in Chinese.
AB  - PURPOSE: Ultraviolet irradiation is known to cause oxidative DNA damage and is
      thought to be a major factor implicated in the pathogenesis of pterygium. The
      highly mutagenic 8-hydroxy-2'-deoxyguanosine, a marker for the evaluation of
      photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I
      (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the
      hOGG1 gene is associated with the substitution of cysteine for serine at codon
      326. In this study, we investigated the association of the hOGG1 Ser326Cys
      polymorphism with pterygium in a Chinese population. METHODS: In all, 70 patients
      and 86 controls were enrolled in this study. The Ser326Cys polymorphism was
      determined by the polymerase chain reaction-restriction fragment-length
      polymorphism analysis. The association between this genetic polymorphism and risk
      of pterygium was examined by chi(2)-test and logistic regression. RESULTS: The
      allelic frequencies for the Ser and Cys variants of hOGG1 gene were not
      significantly different between the two groups. However, when compared with
      Ser/Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys
      genotype was more prevalent in pterygium patients than controls (P=0.024) with
      the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age
      of patients with the Cys/Cys genotype was younger than those with the other two
      genotypes (P=0.025). CONCLUSIONS: Our findings suggest that the 1245C --> G
      transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution
      of the enzyme, might play a role in the susceptibility of humans to pterygium.

PMID- 14716325
TI  - Self-sealing sclerotomies in pars-plana vitrectomy: a prospective evaluation of
      peroperative complications.

PMID- 14716326
TI  - Photodynamic therapy of subretinal neovascularization in radiation retinopathy.

PMID- 14716327
TI  - Fluorescein angiography and patchy skin discoloration: a case report.

PMID- 14716328
TI  - Wegener's granulomatosis of the orbit in a 5-year-old child.

PMID- 14716329
TI  - Massive subretinal haemorrhage secondary to age-related macular degeneration in a
      patient with idiopathic thrombocytopenic purpura.

PMID- 14716330
TI  - Open-angle glaucoma and systemic thyroid disease in an older population: The Blue
      Mountains Eye Study.
AB  - PURPOSE: To assess whether thyroid disease is independently associated with open
      angle glaucoma (OAG), using history of thyroid disease and current thyroxine use.
      METHODS: The Blue Mountains Eye Study examined 3654 persons, aged 49-97 years.
      Interviewers collected self-reported history of diagnosis and treatment for
      thyroid disease. Eye examinations included applanation tonometry, stereoscopic
      optic disc photography and automated perimetry. OAG was diagnosed from the
      presence of matching typical glaucomatous field changes and optic disc cupping,
      independent of intraocular pressure. Associations between thyroid disease
      (history and treatment) and OAG were assessed in a multivariate model. RESULTS:
      Of 324 participants (8.9%) reporting history of thyroid disease, 147 (4.0%) were
      currently using thyroxine. Although we could not accurately categorize the
      thyroid disorder for all cases, current use of thyroxine suggests a prior
      hypothyroid state. All thyroid disease subgroups affected women more frequently
      than men, P=0.001. OAG was diagnosed in 108 subjects (3.0%) and was more frequent
      in those reporting past thyroid disease (4.6 vs 2.8%). This relationship was not
      statistically significant after adjusting for potential confounders, multivariate
      odds ratio (OR) 1.6; 95% confidence interval (95% CI) 0.9-2.9. OAG was
      significantly more frequent, however, in subjects reporting current thyroxine use
      (6.8 vs 2.8%), multivariate OR 2.1; 95% CI 1.0-4.4, or history of thyroid surgery
      (6.5 vs 2.8%), multivariate OR 2.5; 95% CI 1.0-6.2. CONCLUSIONS: This population
      based study suggests that thyroid disease, indicated by current thyroxine use or
      past thyroid surgery, could be independently related to OAG.

PMID- 14716331
TI  - High-altitude flight retinopathy.

PMID- 14716332
TI  - Retinal haemorrhages in an infant following RetCam screening for retinopathy of
      prematurity.

PMID- 14716333
TI  - Why outpatient initiative clinics fail to deliver: an analysis by mathematical
      model.

PMID- 14716334
TI  - Corneal endothelial transplantation using femtosecond laser technology.

PMID- 14716335
TI  - Referrals for cataract surgery: variations between different geographic areas
      within a Welsh Health Authority.
AB  - AIM: The aim of the study was to identify variations in cataract presentation
      within three different eye units in a single health authority and to identify any
      correlation between cataract presentation and social deprivation indices. We also
      compared our patient profile and results with the UK National Cataract Audit
      Statistics. METHODS: It was a prospective multicentre questionnaire-based project
      involving three hospitals: Cardiff Eye Unit--University Hospital of Wales (UHW),
      Royal Glamorgan Hospital--Llantristant (RGH), and Prince Charles Hospital-
      Merthyr Tydfil (PCH). Demographic, clinical, and socioeconomic data were
      collected in patients undergoing cataract surgery. Patients were also asked to
      fill in the questionnaire based on Berth-Petersen Visual Function Index (VF-14)
      indicating difficulty in performing daily living activities. RESULTS: A total of
      112 patients were recruited in the study. Demographics were similar to National
      Cataract Audit. However, the percentage of patients with poor visual acuity (less
      than 6/60) at the time of surgery was greater at all the three hospitals compared
      to the national statistics. Among the three hospitals at South Wales, PCH had the
      lowest visual acuity in both listed and fellow eye and the lowest VF-index. Both
      the outpatient and surgery waiting times were longest at PCH. The population at
      PCH also visited their optician least frequently. CONCLUSION: Our results show
      significant variation in cataract presentation between the three eye units within
      a single Health Authority. These variations correlate well with social
      deprivation indices and poor use of Optometric services. Local policies are
      needed to redress these inequalities and raise public and professional awareness
      of causes of poor sight in the elderly population.

PMID- 14716336
TI  - Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and
      suppress T-cell activation.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) are known to interact with
      hematopoietic stem cells (HSCs) and immune cells, and represent potential
      cellular therapy to enhance allogeneic hematopoietic engraftment and prevent
      graft-versus-host disease (GVHD). We investigated the role of human MSCs in NOD
      SCID mice repopulation by unrelated human hematopoietic cells and studied the
      immune interactions between human MSCs and unrelated donor blood cells in vitro.
      When hematopoietic stem cell numbers were limited, human engraftment of NOD-SCID
      mice was observed only after coinfusion of unrelated human MSCs, but not with
      coinfusion of mouse mesenchymal cell line. Unrelated human MSCs did not elicit T
      cell activation in vitro and suppressed T-cell activation by Tuberculin and
      unrelated allogeneic lymphocytes in a dose-dependent manner. Cell-free MSC
      culture supernatant, mouse stromal cells and human dermal fibroblasts did not
      elicit this effect. These preclinical data suggest that unrelated, human bone
      marrow-derived, culture-expanded MSCs may improve the outcome of allogeneic
      transplantation by promoting hematopoietic engraftment and limiting GVHD and
      their therapeutic potential should be tested in clinic.

PMID- 14716337
TI  - Acute myelogenous leukemia in a donor after granulocyte colony-stimulating factor
      primed peripheral blood stem cell harvest.
AB  - This article describes the first case of acute myeloid leukemia (AML) in a
      healthy donor at 14 months after granulocyte colony-stimulating factor (G-CSF)
      primed peripheral blood stem cell (PBSC) harvest. In September 2001, a healthy 61
      year-old female was given G-CSF prior to PBSC harvest for her brother with
      multiple myeloma. In spite of successful engraftment, the recipient died from a
      disease relapse. In November 2002, the donor, admitted with high fever and
      leukocytosis with 98.5% blastoid cells, was diagnosed as having AML (M1). Her
      leukemia cells were positive for CD13, CD33, and G-CSF receptor without
      chromosomal abnormality and responded to G-CSF in vitro. During chemotherapy, she
      died of progressive pneumonia. If our case is truly the first, the incidence of
      leukemia in donors may not be higher than that of naturally occurring leukemia.
      However, efforts towards an international long-term study, or at least to report
      every case similar to ours, would be required to be conclusive.

PMID- 14716338
TI  - Bone marrow transplantation from partially HLA-mismatched family donors for acute
      leukemia: single-center experience of 201 patients.
AB  - Between February 1993 and December 1999, 201 patients (1-59 years old, median 23)
      with acute leukemia (67% not in remission) underwent ex vivo T-cell-depleted
      (TCD) bone marrow transplants (BMT) from partially mismatched related donors
      (PMRD; 92% mismatched for 2-3 HLA A, B, DR antigens). Conditioning comprised
      total body irradiation, cyclophosphamide, cytarabine, etoposide, anti-thymocyte
      globulin (ATG), and methylprednisolone. Graft-versus-host disease (GVHD)
      prophylaxis comprised partial TCD with OKT3 (n=143) or T10B9 (n=58), steroids,
      ATG, and cyclosporine. The engraftment rate was 98%. The cumulative incidences of
      grades II-IV acute GVHD and chronic GVHD were 13 and 15%, respectively. The 5
      year cumulative incidences of relapse and transplant-related mortality (TRM) were
      31 and 51%, respectively. The actuarial 5-year overall survival (OS) and disease
      free survival (DFS) probabilities were 19 and 18%, respectively. Patient age >15
      years, active disease at transplant, donor age >25 years, and 3-antigen donor
      mismatch (host-versus-graft) affected the outcome adversely. The actuarial 5-year
      OS of four groups of patients identified based upon these risk factors was 39,
      20, 13, and 0%, respectively (P<0.0001). We conclude that PMRD BMT is a potential
      treatment option for patients with high-risk acute leukemia who require an
      alternative donor transplant and fall into a group with a reasonable expected
      outcome.

PMID- 14716339
TI  - Autologous peripheral blood stem cell transplantation with BCVAC conditioning in
      childhood acute myeloid leukemia.
AB  - Autologous peripheral blood stem cell transplantation (APBSCT) after intensifying
      conditioning is one of the post-remission therapeutic options in childhood acute
      myeloid leukemia (AML) patients without a matched family donor, but the optimal
      conditioning regimen has not been defined. This study was performed to evaluate
      the efficacy of a novel conditioning regimen without busulfan or total body
      irradiation. In total, 28 children with AML underwent APBSCT with BCVAC (BCNU,
      etoposide, cytosine arabinoside and cyclophosphamide) conditioning regimen during
      first remission. The event-free survival rate was 71.43% for all patients and the
      only cause of treatment failure was relapse. Eight male patients recurred at 1-11
      months (median 5 months) after APBSCT. One patient remains alive with salvage
      therapy after relapse. With the exception of fever, mucositis and diarrhea, no
      serious complications occurred during APBSCT, including veno-occlusive disease
      (VOD), and there was no transplantation-related mortality. One patient developed
      secondary MDS after APBSCT but recovered hematologically on medication. APBSCT
      with BCVAC conditioning was found to be a safe and effective alternative option
      for patients with childhood AML in first remission, without a matched family
      donor.

PMID- 14716341
TI  - Clinical responses following nonmyeloablative allogeneic stem cell
      transplantation for renal cell carcinoma are associated with expansion of CD8+
      IFN-gamma-producing T cells.
AB  - Nonmyeloablative allogeneic stem cell transplantation (NST) is thought to be an
      immunologic therapy in which donor T cells mediate a graft-versus-tumor effect.
      We recently reported the clinical outcome of a phase II trial of NST in
      metastatic renal cell carcinoma (RCC). However, the immune response correlates of
      clinical activity remain unknown. We now describe the analysis of T-cell subsets
      and T-cell cytokine-producing potential for those patients evaluable for immune
      monitoring. The incidence of graft-versus-host disease (GVHD) correlated with
      clinical outcome, with all responders exhibiting chronic GVHD. Following initial
      tapering of immunosuppression, an increase in the total numbers of CD8+ T cells
      but not CD4+ T cells was observed among responders compared to nonresponders. In
      addition, a greater ratio of CD8+ to CD4+ T cells producing IFN-gamma and IL-2
      was seen in clinical responders at the time when clinical responses were first
      detected (day 180 after transplantation). Our results support the hypothesis that
      the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells,
      and indicate that isolation of putative tumor antigen-specific T cells, ideally,
      should be pursued around day +180.

PMID- 14716340
TI  - Preemptive treatment of minimal residual disease post transplant in CML using
      real-time quantitative RT-PCR: a prospective, randomized trial.
AB  - Immunotherapy in the form of donor lymphocyte infusions in early-phase relapse
      might be advantageous as it induces a higher response, but this may be offset by
      increased toxicity, especially during the early period after transplantation.
      Among 45 consecutive patients receiving an allograft for CML, 13 patients were
      diagnosed to have molecular relapse (MRel), as defined by real-time quantitative
      reverse transcriptase-polymerase chain reaction, and another four patients were
      diagnosed to have cytogenetic relapse (CRel) within 6 months. Patients with MRel
      were randomly assigned to either a 'no therapy' group (group A, n=6), in which
      immunotherapy was reserved until CRel, or an 'immunotherapy' group (group B,
      n=7). In group A, all MRel progressed to CRel, and molecular remission (MR) was
      achieved in four (67%) after immunotherapy. The remaining two patients died of
      extensive GVHD and fungal pneumonia. In group B, only two MRel progressed to CRel
      and the remaining five (71%) achieved MR. Two patients died in the absence or
      loss of response. In patients relapsing directly into CRel (n=4), immunotherapy
      induced MR in two patients (50%). Earlier intervention played a role in
      preventing disease progression but this effect was not translated into better
      survival, which could have been overcome by imatinib mesylate, which induced MR
      and cytogenetic remission in nonresponders without toxicity.

PMID- 14716342
TI  - Reduced-intensity conditioning with busulfan and fludarabine with or without
      antithymocyte globulin in HLA-identical sibling transplantation--a retrospective
      analysis.
AB  - It is unknown whether the addition of antithymocyte globulin (ATG) to reduced
      intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in
      HLA-identical sibling transplantation. Therefore, we analyzed retrospectively
      data on 83 patients, who received peripheral blood stem cells from HLA-identical
      siblings after conditioning with either 8 mg/kg BU and 150 mg/m2 FLU (n=45) or 8
      mg/kg BU, 180 mg/m2 FLU and 40 mg/kg ATG (n=38). Graft-versus-host disease (GVHD)
      prophylaxis consisted of CSA alone (n=32) or a combination with either MTX or MMF
      (n=51). The median age was 52 years. Graft failure occurred in two patients after
      BU/FLU and in three after BU/FLU/ATG (P=0.66). After conditioning with BU/FLU,
      platelet recovery was significantly faster (P=0.017), and less platelet (P<0.001)
      and red blood cell (P=0.002) support was needed. Incidences of acute GVHD grades
      II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often
      after BU/FLU compared to BU/FLU/ATG (54 vs 23%, P=0.02). The overall survival,
      non-relapse and relapse mortality did not differ significantly. We conclude that
      in peripheral blood stem cell transplantation from HLA-identical siblings after
      reduced-intensity conditioning with BU and FLU, ATG has no major impact on the
      rate of graft rejection and acute GVHD, but it reduces the incidence of limited
      chronic GVHD.

PMID- 14716343
TI  - Autologous del(20q)-positive erythroid progenitor cells, re-emerging after DLI
      treatment of an MDS patient relapsing after allo-SCT, can provide a normal
      peripheral red blood cell count.
AB  - A 54-year-old RhD-negative male with del(20q)-positive myelodysplastic syndrome
      was transplanted with bone marrow from an HLA-identical RhD-positive sibling
      donor. Cytogenetic relapse was detected 21 months after stem cell transplantation
      (SCT), with reappearance of the original del(20q)-positive clone and reversion to
      recipient RhD-negative blood group. The patient received sequential donor
      lymphocyte infusions (DLIs), resulting in mild graft-versus-host disease and pure
      red cell aplasia. At 2 years post DLI, the patient remains in a stable condition,
      despite a dominance of recipient-derived erythro- and granulopoiesis originating
      in del(20q)-carrying progenitor cells. We conclude that reappearance of
      autologous erythropoiesis, upon relapse after allogeneic SCT, may be predictive
      of erythropenia after DLI and that re-emerging autologous del(20q)-positive
      erythropoiesis post DLI can provide a normal peripheral red blood cell count.
      Furthermore, in patients relapsing after blood-group-mismatched transplantation,
      a possible reversion to recipient blood group should be considered prior to blood
      transfusion or DLI.

PMID- 14716344
TI  - A single prior course of BCNU-cisplatin chemotherapy has a significant
      deleterious effect on mobilization kinetics of otherwise untreated patients.
AB  - Extensive prior treatment with cytotoxic agents is associated with impaired
      mobilization of hematopoietic cells. To assess the effect of a single course of
      standard-dose chemotherapy (CT), we compared the results of filgrastim-induced
      mobilization among two sequential groups of grade III-IV malignant glioma
      patients included in a hematopoietic transplantation program. The first group (21
      patients) had never been treated with CT until 2 days after surgery, when they
      received a course of 100 mg/m2 BCNU (i.v.) and 100 mg intracarotid cisplatin for
      cytoreduction (not for mobilization). At 1 month after this CT, they were
      mobilized with 12 microg/kg filgrastim. The second group (22 patients) was
      mobilized with the same dose of filgrastim directly after the surgery, without
      having ever received any prior CT. The blood level of CD34+ cells was
      significantly lower in the CT-treated patients, both on the fourth day of
      filgrastim (15 vs 36 cells x 10(6)/l; P=0.01) and on the fifth (25 vs 58 cells x
      10(6)/l; P=0.003), as it was the number of CD34+ cells collected per apheresis
      (1.3 vs 3.5 x 10(6)/l; P<0.0005). The toxic effect of a single course of BCNU
      cisplatin CT led to significant impairment of the filgrastim-induced mobilization
      response.

PMID- 14716345
TI  - Donor lymphocyte infusion to treat relapse after allogeneic bone marrow
      transplantation for myelodysplastic syndrome.
AB  - Donor lymphocyte infusion has become established as a salvage therapy for
      patients with hematological disorders relapsing after allogeneic bone marrow
      transplantation (BMT). The role of donor lymphocyte infusion for patients with
      myelodysplastic syndrome (MDS) remains to be established. Between July 1993 and
      October 2001, 14 patients with MDS relapsing after allogeneic BMT received DLI as
      salvage therapy. At the time of BMT, one patient had RA, nine had RAEB, of whom
      three were in CR after induction-type chemotherapy, two had RAEB-T, one had CMML
      and one had AML. Donors were HLA-matched siblings (n=12), HLA-matched other
      relative (n=1) and unrelated (n=1). At the time of relapse, the median marrow
      blast count was 9%. The median CD3+ cell dose administered was 6.3 x 10(7)/kg.
      With a median follow-up of 49 months, six patients were alive, of whom two were
      in CR after DLI alone and remained disease-free, two were in CR after a second
      BMT and two had active disease. Eight patients died of disease progression.
      Although DLI alone seems to be effective in a small number of patients with MDS,
      other treatment strategies, including prior debulking chemotherapy, deserve
      investigation.

PMID- 14716346
TI  - Quality of life changes following peripheral blood stem cell transplantation and
      participation in a mixed-type, moderate-intensity, exercise program.
AB  - The purpose of this investigation was to evaluate the impact of undertaking
      peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and
      to determine the effect of participating in a mixed-type, moderate-intensity
      exercise program on QoL. It was also an objective to determine the relationship
      between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the
      CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test,
      pretransplant (PI), post transplant (PII) and following a 12-week intervention
      period (PIII). At PII, 12 patients were divided equally into a control or
      exercise intervention group. Undergoing a PBST was associated with a
      statistically but not clinically significant decline in QoL (P<0.05). Following
      the intervention, exercising patients demonstrated an improved QoL when compared
      with pretransplant ratings (P<0.01) and nonexercising transplant patients
      (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The
      findings demonstrated that exercise participation following oncology treatment is
      associated with a reduction in the number and severity of endorsed problems,
      which in turn leads to improvements in global, physical and psychosocial QoL.
      Furthermore, a relationship between fitness and QoL exists, with those
      experiencing higher levels of fitness also demonstrating higher QoL.

PMID- 14716347
TI  - Long-term pulmonary function abnormalities and survival after allogeneic marrow
      transplantation.
AB  - We studied long-term pulmonary function testing (PFT) in a retrospective cohort
      of 6-month survivors of allogeneic marrow transplant (BMT) between 1980 and 1997.
      Of 593 patients, 73, 71 and 65% had adequate data to assess for obstruction,
      restriction and diffusion impairments respectively. Over 5 years, mean declines
      in 1-s forced expiratory volume/forced vital capacity (FEV1/FVC), total lung
      capacity (TLC) and diffusion were 4, 7 and 17%, respectively. TLC and diffusion
      tended to subsequently increase. In all, 6, 12 and 35% of patients met criteria
      for obstruction, restriction and impaired diffusion, respectively. Obstruction
      was less common in recent transplants (5 vs 15%, P=0.004), while restriction and
      diffusion impairment rates remained stable. There was significantly greater
      mortality with obstruction (HR 2.0 (1.04-3.95)), and a nonstatistically
      significant higher mortality rate with restriction (HR 1.6 (0.95-2.75)), but not
      with impaired diffusion (HR=0.99 (0.65-1.50)). cGVHD (OR 16.7 (2.2-129.8)) and
      busulfan (OR 2.9 (1.01-8.24)) were associated with obstruction. Marrow from
      nonsibling or mismatched donors (OR 4.9 (2.2-10.7)) was associated with
      restriction. In summary, after BMT, decreased diffusion capacity is common and
      benign; obstruction has decreased in frequency, is rare without cGVHD, and is
      associated with mortality; nonsibling and mismatched donor are risk factors for
      restriction.

PMID- 14716348
TI  - Subnormal androgen levels in young female bone marrow transplant recipients with
      ovarian dysfunction, chronic GVHD and receiving glucocorticoid therapy.
AB  - Ovarian function and sex hormone production with special focus on androgens
      (testosterone, androstenedione, dehydroepiandrosterone and its sulfate, DHEAS)
      was followed up during 1.5-20 (mean 9) years after bone marrow transplantation
      (BMT) in 24 female subjects aged 16-33 (mean 21) years at the last follow-up. All
      patients had received TBI and high-dose chemotherapy as the preparative regimen.
      A total of 24 female patients with conventionally treated pediatric hematologic
      malignancies served as controls. Four of 24 transplanted patients had spontaneous
      menstruation several years post transplantation, but in only one of them were
      serum FSH levels normal. Androgen levels of the BMT patients were lower than
      those of the conventionally treated patients. Subnormal testosterone levels were
      observed in 43% of BMT patients and subnormal DHEAS levels in 34% of BMT
      patients, the latter being a constant finding during glucocorticoid therapy for
      chronic GVHD (cGVHD). These results indicate that ovarian damage is a common late
      effect in patients transplanted at a young age, still having a seemingly normal
      pubertal development. Ovarian damage and cGVHD with glucocorticoid therapy are
      strongly associated with subnormal androgen levels. The clinical consequences of
      these changes and possible benefits of putative androgen replacement therapy
      remain to be elucidated.

PMID- 14716349
TI  - Role of quantitative human cytomegalovirus PCR in predicting antiviral treatment
      response among high-risk hematopoietic stem-cell transplant recipients.

PMID- 14716350
TI  - Increased incidence of acute graft-versus-host disease with the continuous
      infusion of cyclosporine A compared to twice-daily infusion.
AB  - We retrospectively compared the incidence of acute graft-versus-host disease
      (GVHD) before and after September 1999, when we changed the mode of cyclosporine
      A (CsA) administration from twice-daily infusions (TD) (n=58) to continuous
      infusion (CIF) (n=71). The incidence of grade II-IV acute GVHD in the CIF group
      (56%) was significantly higher than that in the TD group (27%, P=0.00022).
      Multivariate analysis identified only two independent significant risk factors
      for the development of grade II-IV acute GVHD; CIF of CsA (relative risk 2.59,
      95% CI 1.46-4.60, P=0.0011) and the presence of HLA mismatch (2.01, 95% CI 1.15
      3.53, P=0.014). The incidence of relapse was significantly lower in the CIF group
      when adjusted for disease status before transplantation (0.41, 95% CI 0.18-0.95,
      P=0.038), which resulted in better disease-free survival in high-risk patients
      (43 vs 16% at 2 years, P=0.039), but not in standard-risk patients (72 vs 80%,
      P=0.45). CIF of CsA with a target level of 250-400 ng/ml may not be appropriate
      for GVHD prophylaxis in standard-risk patients.

PMID- 14716351
TI  - Improved detection of clinically significant host-reactive antigens prior to HLA
      identical sibling peripheral blood stem cell transplantation using a dendritic
      cell-based helper T-lymphocyte precursor assay.
AB  - SUMMARY: Graft-versus-host disease (GVHD) due to host-reactive antigenic
      differences between HLA-identical pairs remains an important cause of morbidity
      and mortality after allogeneic transplantation. The helper T-lymphocyte precursor
      (HTLp) assay, using peripheral blood mononuclear cells (PBMCs), has been variably
      shown to detect such host-reactive differences. We assessed whether using
      dendritic cells (DCs) as the stimulator cells would improve the ability of the
      HTLp assay to detect these differences. We used PBMCs (standard HTLp assay) or
      monocyte-derived DCs (DC-HTLp assay) as the stimulator cells for 12 HLA-identical
      sibling pairs undergoing allogeneic peripheral blood stem cell transplantation.
      HTLp frequencies were greater by the DC-HTLp assay (median 1:77 712 vs 1:727 514;
      P=0.008). The standard HTLp assay did not predict for acute GVHD (P=0.42),
      whereas a trend was noted for the DC-HTLp assay (P=0.095). Of note, of seven
      patients developing moderately severe to severe acute GVHD, four had a
      significantly greater DC-HTLp frequency compared to the standard HTLp frequency,
      whereas all four patients who developed no to moderate acute GVHD had similar
      HTLp frequencies whether PBMCs or DCs were used as the stimulator cells. Although
      the small number of donor/recipient pairs assessed limits the strength of any
      conclusions, our study suggests that the DC-HTLp assay is better able to detect
      clinically significant host-reactive antigenic differences between HLA-identical
      siblings.

PMID- 14716352
TI  - Autologous blood pleurodesis for pneumothorax complicating graft-versus-host
      disease-related bronchiolitis obliterans.
AB  - Bronchiolitis obliterans (BO) is a manifestation of chronic graft-versus-host
      disease (GVHD) after allogeneic haemopoietic stem cell transplantation.
      Complications associated with this include persistent air-leak syndromes such as
      pneumothorax. Many methods have been described for treating this condition, both
      surgical and nonsurgical. We describe an 8-year-old boy with acute lymphoblastic
      leukaemia complicated by chronic GVHD-related BO, and subsequent pneumothorax
      with persistent air leak, who was treated successfully with autologous blood
      pleurodesis.

PMID- 14716354
TI  - Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone
      marrow transplantation.
AB  - Our purpose was to evaluate frequency and severity of bone mineral decrements and
      frequency of osteonecrosis in survivors of pediatric allogeneic bone marrow
      transplantation (alloBMT). We retrospectively reviewed demographic information,
      treatment, magnetic resonance (MR) imaging studies (hips and knees), and bone
      mineral density (BMD) studies of 48 patients as measured by quantitative computed
      tomography (QCT). In all, 24 patients were male; 37 were Caucasian. Median age at
      alloBMT was 10.3 years (1.6-20.4 years). Of the 48 patients, 43 underwent QCT.
      Median time between alloBMT and imaging was 5.1 years (1.0-10.2 years). Median
      BMD Z-score was -0.89 (-4.06 to 3.05). BMD Z-score tended to be associated with
      female sex (P=0.0559) but not with age at BMT, race, primary diagnosis, time from
      alloBMT, T-cell depletion of graft, total-body irradiation, or acute/chronic
      graft-versus-host disease (GVHD). MR showed osteonecrosis in 19 of 43 (44%). We
      found no associations between osteonecrosis and sex, race, diagnosis, age at BMT,
      history of GVHD, time from BMT, or T-cell depletion. Seven patients (15%) had MR
      changes of osteonecrosis and BMD Z-scores of less than -1 s.d. We conclude that
      pediatric alloBMT survivors have decreased BMD and are at risk of osteonecrosis.
      They should be monitored to assure early intervention that may ameliorate adverse
      outcomes.

PMID- 14716355
TI  - [Physiology and bone physiopathology].
AB  - The bone tissue is one of the largest of the organism, with clear functions: to
      serve as a support and protection for the soft parts, as support for movement
      with the anchorage of the muscles, as mineral reserve and as interactive storage
      of the bone marrow. To exercise all these functions the bone must maintain its
      quality, a concept that combines its degree of mineralisation, its
      microarchitecture and its capacity to repair lesions, aspects that are included
      in the broad definition of osteoporosis: "A systemic disease of the skeleton,
      characterised by a low bone mass and a deterioration of the microarchitecture of
      the bone tissue, which jointly result in an increase in bone fragility and the
      consequent increase of the risk of fractures", although from the clinical point
      of view we have to centre our attention on mineralisation, a quantifiable aspect,
      understanding as osteoporosis a fall in bone mass greater than 2.5 standard
      deviations below that of young healthy patients. This article reviews the
      physiopathological aspects that influence the development of this frequent
      clinical picture.

PMID- 14716356
TI  - [Bone mineral density measurement techniques].
AB  - Different techniques for measuring bone mass density developed in the last years
      are revised. Single and dual fotonic absorciometry are now outdated by the use of
      single and dual x-ray absorciometry which don't need an isotope source. The most
      widely used technique now is the dual energy x-ray asbsorciometry, specially the
      ones who analyse lumbar spine and hip. It is an accurate and precise tool and has
      proved to be a good predictor of fractures. Nevertherless, peripheral
      densitometers based on dual energy x-ray or on broadband ultrasonic attenuation,
      have also proved to be of utility. Quantitative computed tomography is the only
      three-dimensional densitometer available, capable to selectively measure cortical
      or trabecular bone. It has the inconvenient of the high radiation and cost. We
      argue about advantages and disadvantages of the different techniques of bone mass
      measurements.Lastly, we revise the indications of densitometry. There are not
      unanimous criteria about this question, but different organisms and scientific
      societies have elaborated recommendations based on risk factors of osteoporosis
      and fracture, that could be of utility in clinical practice.

PMID- 14716357
TI  - [Classification of osteoporosis. Risk factors. Clinical manifestations and
      differential diagnosis].
AB  - The fact that there are multiple factors that can intervene in the ethiopathology
      of osteoporosis, together with its scarce clinical expression until complications
      -fractures- are produced, poses a practical problem in medical practice when it
      comes to identifying those persons at risk of osteoporosis. These aspects,
      together with the difficulties in obtaining access to a complementary test that
      would confirm the diagnosis and the overload of tasks in our clinic, mean that
      the disease often passes unnoticed. Hence, in the section on diagnostic
      orientation of osteoporosis we attempt to clarify and give cohesion to this
      approach, offering highly useful guidelines for suspecting the presence of the
      disease and patterns of action that will make it possible to diagnose in a more
      efficient and accurate way

PMID- 14716358
TI  - [Secondary osteoporosis].
AB  - Secondary osteoporosis is caused by pathologies or medications, differing from
      the bone loss explainable by the post-menopausal stage or by ageing. The possible
      pathologies that can condition the loss of bone mass are very varied:
      endocrinological, digestive, genetic, haematological, rheumatic, post-transplant,
      pharmacological and a wide miscellaneous group. This article essentially reviews
      the endocrinological causes, with special emphasis on the more controversial
      aspects, followed by a clinical approach for the systematic diagnosis of these
      pathologies, which are frequent in cases initially labelled as primary
      osteoporosis

PMID- 14716359
TI  - [Glucocorticoid induced osteoporosis].
AB  - Glucocorticoids are a group of drugs widely used in medical practice due to their
      unquestionable utility. Corticoid-induced osteoporosis is the main adverse event
      deriving from their systemic and long-term administration, being the most
      frequent cause of secondary osteoporosis. This implies an important health and
      socio-economic repercussion due to the complications it causes, such as fragility
      fractures, above all of vertebral origin, and the resultant functional
      incapacity. The bone loss is produced early, being greatest in the first few
      months of glucocorticoid use, in relation fundamentally to daily dose. The
      pathogenesis of this type of osteoporosis is multifactorial, but the inhibitory
      effect of corticoids on bone formation can be emphasised. The adequate management
      of this serious health problem requires an active attitude that is currently
      suboptimal. It involves similar diagnostic, preventive and therapeutic
      recommendations available for other, different causes of bone loss, but with
      certain particularities, especially including those referring to the self
      management of corticosteroids. A multidisciplinary strategy is advisable, which
      has shown its effectiveness, mainly if it is carried out early, from the start of
      glucocorticoid therapy. Nevertheless, there are many questions to be clarified
      about aspects relating to therapy with corticosteroids in general, and to the
      osteoporosis caused by them in particular. What is needed is the evaluation and
      investigation of new treatments that will improve the effectiveness obtained with
      those in current use, in order to minimize the adverse consequences that
      glucocorticoid use has for the health of patients.

PMID- 14716360
TI  - [Preventive and nutritional factors of osteoporosis].
AB  - In osteoporosis there is a reduction in the protein and mineral matrix of the
      bone, with an increase in the risk of fracture, especially of some bones. The
      present paper discusses some of the preventive factors relating to nutrition and
      life style. The acquisition of bone mass in infancy and adolescence is
      fundamental, carrying out a reasonable amount of exercise and a minimum exposure
      to sunlight, together with a high consumption of calcium proceeding from dairy
      products. The pharmacological supplement of calcium would be justified when the
      ingestion of milk and its derivatives is low in the juvenile and perimenopausal
      ages, as well as in cloistered or institutionalised persons, for whom vitamin D
      supplements should be added. Avoiding the following risks, smoking, the abusive
      consumption of alcohol, intense weight loss and diets that are extremely
      hypercaloric, a sedentary lifestyle and excessive exercise would all be other
      preventive measures for osteoporosis.

PMID- 14716361
TI  - [Treatment of postmenopausal osteoporosis].
AB  - Prevention and treatment of osteoporosis consists of non-drug and drug therapy.
      This review of the topic will provide an overview of the approach to therapy of
      osteoporosis in postmenopausal women. In the past, estrogen replacement was
      considered a primary therapy for the prevention of postmenopausal osteoporosis.
      However, data from the Womens Health Initiative (WHI) revealed that estrogen
      progestine therapy does not reduce the risk of coronary heart disease, and
      increases the risk of breast cancer, stroke, and venous thromboembolic events. As
      a result of these findings, other antiresorptive agents are now the drugs of
      choice for the prevention and treatment of osteoporosis in postmenopausal women.

PMID- 14716362
TI  - [Role of hormone replacement therapy in the prevention and treatment of
      menopausal osteoporosis].
AB  - Hormone replacement therapy has been employed for the prevention and treatment of
      postmenopausal osteoporosis. This paper reviews recently published trials,
      especially the studies Heart and estrogen/progestin replacement study (HERS) and
      Womens Health Initiative (WHI), randomized controlled trials of wide scope. The
      conclusion reached is that hormone replacement therapy has the effect of
      improving the vasomotor symptoms of menopause. It has a positive effect on the
      bone mass with more intensity on the trabecular bone, but this effect only
      persists during the hormonal treatment and the negative balance of bone exchange
      is recovered when treatment stops. A protective effect is found on osteoporotic
      fractures (vertebra, femur) during the treatment of older women (above 60 years),
      but this action is not found in the long term, which is why its value as a
      preventive therapy for osteoporosis is not supported. Finally, certain guidelines
      are given that can be helpful in clinical practice.

PMID- 14716364
TI  - [Health policies in oral health].

PMID- 14716363
TI  - [Drugs prescription for osteoporosis].
AB  - The aim of this study is to analyse the evolution of the global and relative use
      of medicines recommended for osteoporosis during the period between 1998 and 2002
      in Navarra, and their adaptation to present evidence, making reference to the
      differences in the prescription profile in primary and specialised care. To this
      end, information is used from all the prescriptions made within the National
      Health System where one of these medicines is recommended, issued in pharmacies
      of Navarra, and billed to the Navarra Health Service-Osasunbidea. The profile of
      the use of medicines in osteoporosis differs significantly depending on the type
      of specialist who prescribes them. It would be useful to homogenise the approach
      to the prevention of bone fractures. In the period under study the use of
      medicines in Navarra rose by some 85.6% in number of dose/1,000 inhabitants/day.
      The relative use of hormone replacement therapy fell constantly, the employment
      of calcitonins remained steady, undergoing a cyclical profile of peaks in winter
      and valleys in summer, while the relative use of biphosphonates and raloxifen
      tended to increase. There is a need to evaluate the results on health of the use
      of these medicines in clinical practice given the discreet efficacy results
      obtained in clinical trials. Use of calcium should be encouraged because of its
      potential in the prevention of hip fractures against the rest of the medicinal
      alternatives. The relative use of raloxifen and calcitonins seems excessive.

PMID- 14716365
TI  - [Adult stem cells].
AB  - One of the fields of medicine that has created the greatest expectations in
      recent years is cellular therapy with stem cells. The isolation of human embryo
      cells, the apparent and unexpected potential of adult stem cells, and the
      development of gene therapy lead us to imagine a hopeful future for a significant
      number of diseases that are at present incurable. In the following pages we offer
      a sketch of the panorama of research with stem cells, describing the main
      achievements in this field as well as some of the questions awaiting answers. In
      spite of the great expectations, it is essential that we maintain a critical and
      realistic spirit when it comes to analysing the scientific advances in this area.

PMID- 14716366
TI  - [Incorporation of cortical intercalary bone allografts. Experimental study on
      rabbits].
AB  - An experimental study was carried out on 40 rabbits in order to evaluate the
      incorporation of large intercalary bone allografts and the influence of freezing
      on the bone graft. In 36 rabbits resection of 3 centimetres of diaphysis of the
      tibia was carried out and the defect was rebuilt with different types of bone
      graft: fresh autograft and frozen autograft, fresh allograft and frozen
      allograft; osteosynthesis was carried out with two intramedullary Kirschner
      needles. Monthly radiological studies were made until the sacrifice of the
      animals, at 2, 4 and 8 months. A densitometric, histological and diaphanisation
      study of the tibias was made with Spalteholz's technique. In 24 animals 25 mg/kg
      of oxytetracicline was administered 3 and 6 days before sacrifice, to study the
      velocity of bone apposition in the graft. We observed a good and excellent
      radiological consolidation in 80% of the grafts (99% in the autografts and 66% in
      the allografts). The bone density showed a fall until the 4th month due to bone
      reabsorption except in the group of fresh allografts. The revascularization of
      the allografts was slower and poorer than the autografts, but with the same
      vascular pattern. Bone incorporation and neoformation were greater in the
      autografts without significant differences with the frozen allografts. The speed
      of bone apposition did not change with the different types of bone graft used.
      Freezing facilitated and accelerated incorporation and the quantity of bone
      neoformation of the allografts.

PMID- 14716367
TI  - [Clinical complications in a series of patients with anticardiolipin antibodies].
AB  - An analysis was made of clinical complications, determined with objective
      methods, in 68 patients at the University Clinic of Navarra with the clinical
      suspicion of antiphospholipid syndrome (APS) and presence of anticardiolipin
      antibodies (ACA). Patients with IgG higher than 23 GPL were considered for the
      study. The most prevalent pathology was thrombosis: venous thrombosis (42.6%) and
      arterial thrombosis (22%). Other complications were abortions (23.8% of the 42
      women) and thrombocytopenia (12.1%). With respect to the localisation of venous
      thrombosis, predominance corresponded to lower extremities (51.7%), followed by
      superficial thrombophlebitis (27.5%) and pulmonary thromboembolism (20.6%). Among
      the arterial complications, the most frequent were cerebrovascular disease (86.6
      %) and coronary disease (13.4%). There was no correlation between the presence of
      high values of ACA and the prevalence or severity of clinical manifestations. In
      the series of patients with ACA IgG>23 GPL, we appreciated a high percentage of
      venous and arterial thrombosis detected with objective methods. The presence of
      ACA constitutes a prothrombotic risk factor

PMID- 14716368
TI  - [Twelve years of the child oral care program (PADI) in Navarra (1991-2002).
      Utilisation and health indicators].
AB  - BACKGROUND: In 1991, with an incremental character, the Infant Oral Care Program
      (PADI) was set up in Navarra, which covers the population of 6 to 15 years of
      age, and which has a mixed provision, public and private-arranged, the latter
      with a payment system by capitation. The aim of this article is to analyse the
      possible impact of the program on the use of services and to analyse the
      evolution of the dental health of Navarra schoolchildren in the 1991-2002 period.
      MATERIALS AND METHODS: Data was collected on the network of providers and the
      utilisation of the PADI made available by the Directorate of Primary Care of the
      Navarra Health Service - Osasunbidea, and data was analysed from the surveys of
      dental health for 1987, 1997 and 2002, whose methodology has been published. The
      data was exploited statistically with the SPSS program for Windows, v10. RESULTS:
      The number of dentists-providers of the program increased from 28 in 1991 to 161
      in 2002; in the same period the indexes of participation rose from 37.4 to 67.2%.
      There is a positive, statistically significant correlation between the growth of
      the network (r: 0.941) and its geographical extension (r: 0.933), and the index
      of utilisation. The percentage of schoolchildren aged 14 years who state that
      they have been to the dentists in the last year rises from 55.1% in 1987 to 88.2%
      in 2002. More than 70% of the schoolchildren between 6 and 12 years of age state
      that they have been to a PADI dentist. The prevalence of caries continues to fall
      in all age groups and becomes stabilised at 14 years. Between 44 and 79.2% of the
      caries are treated. The schoolchildren who regularly visit the PADI show more
      preventive and restorative treatment (sealed) than those who do not. CONCLUSION:
      The setting up of the PADI seems to have brought an increase in the utilisation
      of the dental services, together with an improvement in the dental health of the
      infant and adolescent population of Navarra.

PMID- 14716369
TI  - [Problems in the use of medicines in enterostomized patients].
AB  - The practice of intestinal stoma, transitory or permanent, has a series of
      implications of a physiological, pharmacological, psychological and communitarian
      character that must be attended to in an integral and individualised way for each
      patient. Frequently, the ostomised patient is subjected to pharmacological
      therapy. However, the foreseeable effect of the medicines administered can be
      affected by factors related to the stoma. Thus, descriptions have been made of
      extensive resections of ileum that affect the process of the oral absorption of
      medicines, especially in pharmaceutical forms of enteric covering, delayed
      release and pills. This would mean access of the unabsorbed portion of the active
      principle to the collecting device through the faeces and a possible alteration
      of the duration and intensity of the pharmacological effect. On the other hand,
      pharmaco surveillance studies have revealed that numerous active principles
      produce changes in intestinal motility, either on the basis of its fundamental
      mechanism of action (laxatives, anti-diarrhoea, prokinetics), or as a collateral
      or secondary effect (antiacids, antidepressants, antihistamines, opioid
      analgesics). The appearance of constipation and, especially, of diarrhoea can be
      disturbing and worrying for ostomised patients, and particularly grave in
      ileostomised patients, due to the dehydration to which it can give rise.
      Similarly, changes in the colour and odour of faeces, secondary to the
      administration of medicines (ferrous salts, aluminium hydroxide, bismuth
      compounds) can needlessly alarm the patients who detect them in the ostomy
      collecting device (pouch). All these factors can create difficulties for the
      adhesion of the patient to the proscribed treatment and, as a result, affect its
      success. However, they can be avoided, corrected or justified with good
      counselling by the health professionals involved in caring for enterostomized
      patient.

PMID- 14716370
TI  - [Psychocognitive stimulation in dementias].
AB  - Alzheimer's disease is a neurodegenerative disorder that provokes a progressive
      loss of memory and of other cognitive functions, with additional symptoms in the
      behavioural and psychological sphere, loss of autonomy and an important
      overburdening for the family and the social milieu. Dealing with this disorder
      and other related dementias requires a multidimensional strategy that is able to
      face the different needs raised by the patient and his family. Given the lack of
      a curative pharmacological treatment, psychosocial interventions have emerged
      over the years that are directed at optimising the function of the patient and
      supporting the family in caring for him, with very different techniques in each
      of the spheres of intervention (cognitive, behavioural, environmental, family).
      In this review, we make a description of the interventions that have been most
      studied in the field of cognitive stimulation, from the most global approaches
      (reality orientation therapy, reminiscence therapy, psychostimulation programs)
      to the most specific ones in the field of memory rehabilitation (training of the
      explicit memory, technique of delayed remembrance, vagueness, error-free
      learning, procedure training of the memory and the use of external help), and the
      results are shown of some studies carried out using these techniques of
      intervention.

PMID- 14716371
TI  - [The Child Oral Care Program (PADI) of Navarra and the Basque Country:
      achievements and new goals].
AB  - This paper briefly analyses the results of the Infant Dental Care Program (PADI)
      of the Basque Country (1990) and Navarra (1991), aimed at children aged from 6
      and 15 years. At the age 12, the lack of caries rose from 31% in 1988 to 57% in
      1998 in the Basque Country, while it was 58% in Navarra (1997); the number of
      caries fell in Navarra by some 64% and by some 54% in the Basque Country, and the
      index of restoration was 81% in Navarra and 73% in the Basque Country (it was 17%
      in 1988). Emphasis is placed on the importance of a good evaluation of these
      programs and the opportunities that are opened up by the comparative analysis
      between Spanish autonomous communities for analysing the contribution of factors
      that are different, and for evaluating the impact of the programs on social
      inequalities in health. The results of the PADI exceed the initial aims of the
      Health Plans of Navarra (1991) and of the Basque Country (1990), and endorse the
      adoption of these programs by the Spanish autonomous communities. The development
      of these programs raises new objectives in dental health policy in Navarra and
      the Basque Country and, above all, makes it necessary to reflect on the need for
      Spain to include public dental health in its health policy and for the National
      Health System as a whole to include dental services within its services

PMID- 14716372
TI  - [Spontaneous bacterial peritonitis and bacteraemia due to Aeromonas hydrophila].
AB  - Bacterial peritonitis is a frequent complication in cirrhotic patients. Amongst
      the aetiological germs, Aeromonas is very infrequent. We present the clinical
      case of a cirrhotic patient with peritonitis and bacteraemia due to Aeromonas
      hydrophila. This micro-organism is a Gram-negative bacillus of the Vibrionaceae
      family. It very frequently produces gastroenteritis in the human being.
      Exceptionally it can give rise to extraintestinal infections, especially in
      immunodepressed patients. Peritonitis due to Aeromonas has been described in
      association with spontaneous bacterial peritonitis in cirrhotic patients, in
      patients on peritoneal dialysis and in cases of peritonitis secondary to
      intestinal perforation.

PMID- 14716373
TI  - [Comparative results of ganglion dissection in cancer of the rectum with and
      without prior treatment of the adipose tissue].
AB  - BACKGROUND: The aim of this study is to describe the result obtained through two
      techniques of isolation of lymphatic lymph nodes in surgical pieces of anterior
      resection due to adenocarcinoma of the rectum. MATERIAL AND METHODS: We carried
      out a search in a series of 30 consecutive cases of patients operated on for
      adenocarcinoma of the rectum for lymph nodes first in a manual conventional way
      and second after 24 hours in a degreasing solution at room temperature. RESULTS:
      In the first search 335 lymph nodes were lymph nodes isolated, with an average
      that oscillated between 6.46 and 17.58, with the lower values corresponding to
      the groups that had received prior adjuvant treatment. In the second inclusion,
      following the action of the clearing solution, we found new lymph nodes (85) in
      some 75% of the cases, appreciably lower in number and smaller in size than the
      initial search. CONCLUSIONS: Manual lymph nodes dissection of the adipose tissue
      is a reliable method for the isolation of lymphatic lymph nodes in pieces of
      resection due to adenocarcinoma of the rectum. The search for lymphatic ganglions
      following the action of a clearing solution should be reserved for cases in which
      the minimum recommended in the TNM staging is not reached

PMID- 14716375
TI  - [Predeposit blood donation in elective surgery at the Hospital of Tudela].

PMID- 14716374
TI  - [Cavernous haemangioma of the small bowel: an uncommon cause of intestinal
      obstruction].
AB  - Cavernous haemangioma of the small bowel is a vascular, benign and infrequent
      tumour, similar in both sexes and more typical from the third decade onwards. Its
      most common clinical manifestation is a chronic anaemia secondary to intestinal
      bleeding, other causes are intestinal obstruction and perforation. Preoperational
      diagnosis is difficult and the treatment of choice is surgical resection.

PMID- 14716376
TI  - [Ethics in the Italian national health service].

PMID- 14716377
TI  - [American Public Health Association: public health code of ethics].

PMID- 14716378
TI  - [Epidemiological monitoring of legionellosis: a case-control study in an
      university general hospital].
AB  - The authors report the early results of a case-control study carried out about
      the risk of legionellosis. During the first year, they have tested urine samples
      from patients with unknown pneumonia, using a legionella-sensitive test for the
      detection of its antigen. Out of 171 samples, 9 have turned out to be positive
      (5.3%). Lifestyles, predisposing factors, possible sources of infection and
      stressful events were investigated.

PMID- 14716379
TI  - [Hygienic monitoring in a municipal solid waste incineration plant].
AB  - Under President's Executive Order 915/1982, the Malagrotta waste disposal plant
      has been surrounded by a water-proof ring. This study reflects a eight-year
      research activity about "the Plant's steadiness and its impact on the land;
      hygienic monitoring of aquifers, air quality control and sound pollution; health
      and safety of workers; disinfection and land reclamation". For surface subsidence
      to be measured, 21 spots were monitored and 30 piezometers were set up in
      adjacent critical areas, both inside and outside the plant. Some of them were
      also used to pick up water and test it for chemical and microbiological purposes.
      Samples of leachates were analysed, air quality assessed and sound tests carried
      out. Overall outcomes show good performance in terms of interaction between
      plant, hydro-geological regimen and possible impact on the surrounding land.

PMID- 14716380
TI  - [Management of the patient's pain in a highly specialized health center].
AB  - The management of pain sensations is useful to enhance technical quality within
      hospitals: this study provides an overview of pain management in a highly
      specialized health center. In 69.6% of cases the patients answers matched with
      those of health staff: the most interesting factor is the health staff's
      willingness to attend training courses aimed at treating the patients pain.

PMID- 14716381
TI  - [Strategies for assessing clinical and veterinary management of a local health
      authority in Central Italy].
AB  - The authors have analyzed the one-year performance of a method aimed at assessing
      clinical and veterinary managements within the complex organization of a health
      unit. There are described methods for assigning organizational offices,
      assessment schemes, criteria and indicators.

PMID- 14716382
TI  - [The NHS health development agency].

PMID- 14716383
TI  - [Two enterprising years].

PMID- 14716384
TI  - [How much should a psoriatic spot cost?].

PMID- 14716385
TI  - [Changes in reporting on passive smoking by parents of small children].
AB  - BACKGROUND: The Norwegian Cancer Society has led a comprehensive information
      campaign since 1995 with the aim of reducing young children's ETS (environmental
      tobacco smoke) exposure in their homes. The aims of the present study were to
      assess changes in parents' reporting of child exposure to ETS, attitudes towards
      ETS, and awareness regarding the potential hazards of passive smoking to
      children. MATERIAL AND METHODS: A questionnaire along with a stamped, addressed
      envelope was sent to a stratified random sample of 1000 households in Norway with
      three-year-old children at the time of the investigation (May 1995 and August
      2001). RESULTS: According to parents, the prevalence of households in which
      children were exposed to ETS fell from 32% in 1995 to 18% in 2001. In both
      surveys, the probability of children being exposed was positively correlated with
      the number of parents smoking and inversely correlated with length of education,
      negative attitudes towards ETS and strength of health-risk awareness.
      INTERPRETATION: The observed changes must be viewed in the light of the media
      focus on passive smoking during this period, a nationwide information campaign
      and as an artifact caused by more underreporting of a behaviour that is being
      internalised as in breach of a norm.

PMID- 14716386
TI  - [Recent knowledge on mechanisms underlying development of pre-eclampsia].
AB  - BACKGROUND: The present paper gives an overview of recent research on mechanisms
      underlying pre-eclampsia. Special attention is paid to immune reactions at the
      feto-maternal site and genetics linked to maternal susceptibility. RESULTS: The
      pathogenesis of pre-eclampsia may be seen as a two-stage process. Deficient
      trophoblast invasion and artery remodelling may underlie subsequent placental
      hypoperfusion. Impaired trophoblast invasion may either be caused by abnormal
      biology of the trophoblast, or increased cytotoxicity of maternal immunocompetent
      cells, or a combination of both. The placental hypoxia/ischaemia (step 1 of the
      pathogenesis) is associated with release of products into the maternal
      circulation, and maternal responses evoked may imply endothelial activation (step
      2). The linkage between the placental disease and the maternal syndrome is still
      a matter of discussion, but more oxidative stress and/or elevated maternal
      inflammatory response has been hypothesised. Maternal susceptibility for
      endothelial activation, hence development of pre-eclampsia, seems to be
      determined by genetic factors. According to recent family linkage studies of the
      whole human genome, a region on chromosome 2 seems to be involved. CONCLUSION:
      Pre-eclampsia develops in the interaction between the placental disease and
      maternal responses. Immune responses appear to underlie the placental disease,
      whereas genetic arrangements determine maternal susceptibility.

PMID- 14716387
TI  - [Restless legs].
AB  - BACKGROUND: Restless legs syndrome is a common and not fully appreciated
      disorder. Improved treatment options require knowledge about the condition.
      MATERIAL AND METHODS: The article is based on a literature search on Medline,
      PubMed and Scirus for the years 1988-2003 with the keyword "restless legs".
      RESULTS AND INTERPRETATION: Restless legs syndrome is a chronic condition defined
      as an irresistible desire to move one's limbs, usually associated with
      paraesthesia/dysaesthesia and motor restlessness. The symptoms start or worsen at
      rest and improve with activity. The prevalence is between 5% and 15%. 80% of
      patients suffer from periodic limb movements in sleep. A current hypothesis is
      that the condition results from a deficiency of iron that lead to the underlying
      dopaminergic abnormalities. Therapeutically, studies have confirmed the effect of
      levodopa and dopamine agonists; dopamine agonists seem to imply less risk of side
      effects.

PMID- 14716388
TI  - [Cryptococcal meningitis].
AB  - BACKGROUND: Cryptococcus neoformans causes systemic disease in patients with
      immunodeficiency. The incidence of cryptococcal meningitis has increased in
      parallel with that of HIV infection. Cancer is also a known predisposing factor.
      MATERIAL AND METHODS: We present two case reports and a review of the literature
      concerning the epidemiology, diagnostics and treatment of cryptococcal
      meningitis. RESULTS: The incidence of cryptococcal meningitis in Scandinavia
      seems to be lower than in other parts of the world. Clinical signs and symptoms
      are often uncharacteristic. Detection of antigen in spinal fluid is a sensitive
      and fast test. INTERPRETATION: Cryptococcal meningitis is a rare disease, often
      with uncharacteristic symptoms. Patients with haematological malignancies have a
      higher risk of contracting this disease. It is a differential diagnosis when
      neurological symptoms occur in these patients.

PMID- 14716389
TI  - [Smoking in upper secondary schools].
AB  - BACKGROUND: The ministers of education and health have called upon county
      councils to use their right of ownership to make upper secondary schools smoke
      free. The aim of this study was to ascertain changes in the proportion of smoke
      free school grounds occurring between 1998 and 2003, to ascertain the number of
      schools that are planning a ban on smoking on school grounds in the immediate
      future, to ascertain difficulties of implementation and to compare smoking
      intensity among students and teachers at schools with different regulatory
      environments. MATERIAL AND METHODS: All headmasters of upper secondary schools in
      Norway were interviewed over the telephone in 1998 and in 2003. RESULTS: Students
      were allowed to smoke on school grounds in 71% of the schools in 2003 as against
      91% in 1998. Three counties had issued regulations for smoke-free schools during
      the period. Most schools in these counties had implemented a smoke-free regime;
      this was the real reason for the national drop. Little change had taken place in
      schools in the rest of Norway. A majority of the headmasters did not plan to
      introduce a smoke-free regime on their own. Eight out of ten wanted the political
      authorities rather than the schools to act as the regulatory body on smoking.
      INTERPRETATION: Regulations issued by the county authorities appear to be a
      necessary, successful and welcome means of implementing a smoke-free environment
      in upper secondary schools.

PMID- 14716390
TI  - [The scale of border trade, tax-free import and tobacco smuggling to Norway].
AB  - BACKGROUND: There are no studies of the relative significance in Norway of
      registered sales, tax-free import, border trade or smuggling of tobacco. MATERIAL
      AND METHODS: The estimated registered sales of tobacco are based on data from the
      Norwegian customs and excise authorities. The border trade and tax-free import
      estimates were based on nation-wide, representative surveys of daily smokers aged
      16-74 carried out by Statistics Norway for the years 1990-1993 and 1997-2001.
      There are no detailed data on the scale of smuggling other than confiscation
      statistics compiled by the customs and excise authorities. It is assumed that
      confiscations amount to about a tenth of the total amount smuggled into the
      country. RESULTS: The unregistered consumption of cigarettes and tobacco has been
      on the rise since the early 1990s; in the years 1997-2001 it accounted for about
      a quarter of total consumption. Broken down, the figures are as follows: 11% was
      purchased in Sweden, 5% in Denmark, 9% in other foreign countries; 1% was
      smuggled into the country. INTERPRETATION: The rise in unregistered tobacco
      consumption is putting further pressure on the high Norwegian taxes on tobacco.
      But if taxes were cut, domestic demand would rise, and hence have little or even
      negative impact on revenue flowing to the government from the legal tobacco
      market and probably little impact on the levels of imported tobacco through tax
      free arrangements or cross-border trade. Hence, although the price gap between
      Norway and neighbouring countries narrows, we must assume that the motivation to
      acquire tobacco will remain unaffected while Norwegians continue to travel to
      Sweden to stock up on inexpensive meat produce.

PMID- 14716391
TI  - [Evaluation of an educational program for adolescents with asthma].
AB  - Knowledge and understanding is important to the quality of life and coping
      ability of adolescents with bronchial asthma. Adolescents are often difficult to
      recruit and retain in educational programmes; the aim of this study was to
      develop and evaluate a modern training programme for adolescents. The two-day
      training programme included question sessions about asthma, lectures, videos,
      demonstrations, searches on the internet, counselling and group discussions. The
      evaluation was based on focus group interviews with 39 adolescents, 13 to 16
      years of age, divided into 7 groups. Adolescents were motivated for learning via
      the internet. The group discussions inspired to confidence and openness about
      one's own disease and medication. The educational model provided motivation for
      self-reliance and autonomy.

PMID- 14716392
TI  - [Do calcium antagonists prevent heart failure in hypertension?].

PMID- 14716393
TI  - [Correction of refractive errors with LASIK].
AB  - Laser in situ keratomileusis (LASIK) is the most prevalent method for correction
      of refraction errors. Within certain limits, all types of refraction errors may
      be treated with excellent accuracy and stability of the corrections. Serious
      complications are rare, but they may be sight-threatening and should be promptly
      dealt with by an ophthalmologist. This paper presents an overview, aimed at the
      general practitioner, of this procedure, indications for it, clinical course, and
      the main complications.

PMID- 14716394
TI  - [Prevalence of refractive errors in Norway].
AB  - BACKGROUND: The aim of this study was to determine the prevalence of refractive
      errors among young and middle-aged adults in Norway. MATERIAL AND METHODS:
      Refractive errors were measured with an autorefractor in a population-based
      sample of young (20-25 years) and middle-aged (40-45 years) adults participating
      in a health study (HUNT) conducted in Nord-Trondelag county in Norway in 1996-97.
      RESULTS: A total of 3137 persons (1248 young and 1889 middle-aged adults) with
      corrected visual acuity >0.5 (in either eye) were included. About half of the
      population (51.8% among the young and 52.3% among the middle-aged adults) were
      emmetropic. The prevalence of myopia was 35.0% in the young adult group and 30.3%
      in the middle-aged group. Myopia was significantly higher in women aged 20-25
      years (36.4%) than in men aged 40-45 years (28.1%). Prevalence of hyperopia
      increased with age from 13.2% (20-25 years) to 17.4% (40-45 years).
      INTERPRETATION: The results show a relative high prevalence of myopia in the
      general population of Norway.

PMID- 14716395
TI  - [Chemical burns to the eye].
AB  - BACKGROUND: Chemical injuries to the eye represent a significant fraction of
      ocular trauma requiring immediate treatment. Severe injuries might lead to
      serious visual impairment. This study reviews the frequency, cause, and results
      of treatment of all cases of chemical eye injuries in patients presenting in the
      section for ophthalmology at St. Olav University Hospital over a three-year
      period. MATERIAL AND METHODS: Records of all patients presenting with ocular
      burns over the 1993 through 1995 period. The records were examined to extract
      information about age, sex, extent of injury, chemical substances involved, place
      of injury, treatment, and frequency of serious visual impairment. RESULTS: Out of
      the 269 cases, 49% occurred in the workplace, 28% at home. Men were involved
      about twice as frequently as women, most of them at work. The majority of women
      were injured at home. Alkalis were the most frequent chemical, implicated in 48 %
      cases, while strong acid caused 20% of the injuries. Use of lye as a bleaching
      agent for wooden materials, cleaning, silo preparation in agriculture, laboratory
      work and work with cement and plaster were activities with high risk of burns to
      the eye. 95% of the patients were treated with eye irrigation before admittance;
      93% were then continually irrigated in hospital (with a mean solution volume of
      19 litres). Serious eye damage following ocular burns was registered in 8
      patients (3%). INTERPRETATION: Most chemical eye burns are mild injuries with no
      lasting adverse effects. Immediate irrigation of the eye is the most important
      treatment. Therapeutic procedures for eye burns should be based on the latest
      research results. Prophylactic efforts should be increased in order to bring down
      the frequency of burns.

PMID- 14716396
TI  - [Age-related macular degeneration].
AB  - Age-related macula degeneration is the most common cause of visual disability in
      the industrialised world. The disease can be diagnosed as a maculopathy in 10-20%
      of the population over the age of 65. About 25% of these will have degeneration
      with reduced vision. Today, only a small proportion of patients with the
      aggressive wet form of the disease can be offered any therapy in the form of
      laser or photodynamic laser treatment. Worldwide epidemiological investigations
      designed to define contributing factors have so far not been conclusive, but the
      use of antioxidants and trace metals may be a useful prophylactic measure.
      Research into antiangiogenic therapy may also result in useful tools for
      ophthalmologists caring for this group of patients.

PMID- 14716397
TI  - [Psoriasis and psoriatic arthritis--is climate therapy a treatment or a leisure
      activity?].
AB  - BACKGROUND: For many years, Norwegian patients with psoriasis or arthritic
      psoriasis have been offered climate therapy. In 2002, Rikshospitalet University
      Hospital's department for treatment abroad organised this treatment for the first
      time for a group of patients with combined psoriasis and arthritic psoriasis.
      MATERIAL AND METHODS: In 50 patients, psoriasis severity (psoriasis area and
      severity index, PASI 0-72) was assessed at start and end of treatment in Turkey.
      Patients reported joint pain (VAS 0-100), skin (DLQI-N 0-29), arthritic psoriasis
      related quality of life (ADI-N 0-33) and functional status of arthritis (MHAQ 1
      4) at arrival, one week and two months after treatment. Standard response mean
      (difference/SD difference) was used to evaluate clinical relevance. RESULTS:
      Disease activity was mild at start of treatment. The clinical relevance for the
      change in skin and arthritis related quality of life was considered high one week
      after treatment and moderate after two months. Change in psoriasis, pain and
      functional status of the joints had little clinic relevance. A statistical
      significant score improvement was found for PASI (6.0 vs. 2.0), DLQI-N (8.4 vs.
      2.2 vs. 4.6), ADI-N (9.9 vs. 4.8 vs. 7.0) and MHAQ (1.6 vs. 1.3 vs. 1.4), all
      means. No significant change in pain score was demonstrated for those having
      arthritic psoriasis. INTERPRETATION: If climate therapy should be implemented as
      supplemental therapy, we recommend recruitment of patients with severe to
      moderate psoriasis and arthritic psoriasis and inclusion of an analysis of cost
      effectiveness.

PMID- 14716398
TI  - [Consumer participation--alibi or reality?].

PMID- 14716399
TI  - [Salutogenesis and empowerment in the perspective of general practice].

PMID- 14716402
TI  - [The difficult choice of mothers].

PMID- 14716404
TI  - [The Hanssen method for measurement of single glomerular filtration rate].
AB  - The human renal function is usually obtained as the sum of filtration of 2
      million glomeruli in both kidneys. Different glomerular size in the deep and
      superficial renal cortex led physiologists to suspect differences in both
      filtration rates and regulation. From 1955 to 1963, a young Norwegian physician,
      Odd E. Hanssen (1917-64) in the department of pathological anatomy at
      Rikshospitalet University hospital in Oslo developed a method for estimating
      single glomerular filtration rate in all layers of the renal cortex of
      experimental animals by determining tubular content of filtered ferrocyanide.
      When testing the method he also made several new observations on tubular
      functions. After a delay of several years, the "Hanssen method" was adopted in 17
      laboratories around the world. In about 50 publications the filtration
      distribution was described in many species under control conditions, during
      varying salt intake, and during exposure to various nervous and humoral stimuli.
      Odd Hanssen did not live to see the widespread use of his method; he died from
      cerebral haemorrhage in 1964 at the age of 47.

PMID- 14716405
TI  - [Patient right when it comes to information].

PMID- 14716406
TI  - [Financing of physicians' services in nursing homes].

PMID- 14716407
TI  - [Competence drain from public health services].

PMID- 14716408
TI  - [Flight to the private sector and ophthalmology].

PMID- 14716409
TI  - [Patient satisfaction as quality indicator of specialist health services].

PMID- 14716410
TI  - [Drug therapy of osteoporosis].

PMID- 14716411
TI  - [A new Nordic mycologic association].

PMID- 14716413
TI  - [How dangerous is passive smoking?].

PMID- 14716417
TI  - [Polyps and gastric carcinoma].

PMID- 14716418
TI  - [Gastric polyps and histological changes in surrounding mucosa].
AB  - PURPOSE: Gastric polyps are elevated epithelial lesions which pathogenesis and
      natural history are not well known. The purpose of this study was to determine
      the association between gastric polyps and histological changes of the
      surrounding mucosa. MATERIAL AND METHODS: Prospective, descriptive and
      transversal study. From 6603 patients examined through upper endoscopy at the
      National Hospital Edgardo Rebagliati Marins (Lima-Peru) from January 2002 to May
      2003,115 gastric polyps were detected (1.74%) 68 of which were included in this
      study. Gastric polyps were examined through endoscopy and thereafter excised,
      taking biopsies of the surrounding mucosa. The histological examination
      established the gastric polyp type and the presence of inflammation, activity
      (infiltration with polymorphonuclears), atrophy, metaplasia, and Helicobacter
      pylori in the surrounding mucosa. RESULTS: Frequency of gastric polyps was as
      follows: hyperplastic: 51 (75%) adenomatous: 11 (16.2%) of fundic glands: 4
      (5.9%) and inflammatory: 2 (2.9%). The mucosa surrounding hyperplastic polyps was
      characterized by the statistically significant presence of inflammation (100%,
      p=0.0001) and activity (84.3%, p=0.001) while the mucosa surrounding the
      adenomatous polyps showed statistically significant presence of inflammation
      (100%, p=0.0001) activity (81.8%, p=0.001), atrophy (72.7%, p=0.017) and
      metaplasia (72.7%, p=0.017). The severity of atrophy and metaplasia was
      significantly higher in the mucosa surrounding adenomatous polyps than in that
      surrounding hyperplastic polyps (p=0.019 and p=0.001). CONCLUSIONS: Hyperplastic
      polyps are associated with the presence of inflammation and activity in the
      surrounding mucosa, whereas adenomatous polyps are associated with the presence
      of inflammation, activity, atrophy, and metaplasia in the surrounding mucosa.
      Atrophy and metaplasia were more severe in the mucosa surrounding adenomatous
      polyps.

PMID- 14716419
TI  - [Transjugular liver biopsy: retrospective study performed on 71 patients].
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy and safety of
      transjugular liver biopsy at the Guillermo Almenara Irigoyen National Hospital -
      EsSalud. MATERIAL AND METHODS: A total of 71 transjugular biopsy cases were
      studied from January 2001 to July 2003 at the Radiology Department, using the
      Cook Quick Core transjugular biopsy needle. Data collected included the patient
      demographic data, transjugular biopsy indications, specimen quality, and
      complications. RESULTS: Transjugular biopsy indications included coagulopathy,
      ascites, and terminal chronic renal failure. Diagnostics efficacy was obtained in
      92.96% of the cases, with 11.27% of minor complications. The mean number of
      portal triads was 6.7, the mean number of specimens was 26, and the mean length
      of the largest fragment was 13.5 mm. CONCLUSION: Transjugular liver biopsy is a
      safe and effective procedure with which adequate samples may be obtained from a
      large number of patients.

PMID- 14716420
TI  - [Immunogenicity and efficacy of a new recombinant DNA vaccine for hepatitis B
      virus in Peru].
AB  - Approximately 350 million persons are infected with Hepatitis B virus around the
      world. Peru is one of the countries with high prevalence of Hepatitis B in Latin
      America and this disease is an important cause of chronic hepatitis, cirrhosis,
      and hepatocellular carcinoma in our country. Vaccination is the only method that
      has proved to be effective in the control of this disease. This is a prospective,
      randomized study performed with the purpose of evaluating immunogenicity and
      efficacy of the Hapavax-Gene vaccine in Peru, a new recombinant DNA vaccine, in
      healthy persons over 10 years of age. The vaccine was applied intramuscularly, on
      the deltoid muscle, in 10 microgram doses, to persons between 10 and 19 years of
      age and 20 microgram doses in persons over 19, using the three doses vaccination
      scheme: day 0, after 30 days and after 180 days. Out of a total of 188 persons
      initially admitted for this test, 67 persons completed the study. Immunogenicity
      was satisfactory: 100% of the participants of Group A (10 to 19 years of age) and
      100% of the participants of Group B (over 19). With an arithmetical mean of
      28,583.92 mlU/mL and a geometrical mean of 5,754.32 mlU/mL in Group A and an
      arithmetical mean of 8,708.3 mlU/mL 2 and a geometrical mean of 2,179.32 mlU/mL
      in Group B. Adverse events accounted for 4.69%, none of which was severe. The
      recombinant DNA vaccine derived from H. Polymorpha applied in three doses on day
      0, after 30 days and after 180 days, is immunogenic and safe in healthy Peruvians
      over 10 years of age.

PMID- 14716421
TI  - [Hepatitis C virus infection in female sexual workers from northern Lima].
AB  - Hepatitis C is the second major endemic viral infection in the world after HIV.
      In the USA it is the first liver transplant indication. Currently, the main risk
      factors to develop this disease are history of blood transfusions and IV drug
      usage. Sexual transmission remains controversial and accounts probably for less
      than 5% of case transmissions. PURPOSE: Determine the prevalence of hepatitis C
      virus infection in female sexual workers from Northern Lima and identify other
      risk factors. MATERIAL AND METHODS: A prospective study was performed in female
      sexual workers from Northern Lima. Risk factors were assessed in a survey; at the
      time of the assessment they were HIV negative. The COBAS CORE Anti-HCV EIA II
      Test was used. RESULTS: HCV serology was negative in all 98 sexual workers. 90%
      used protection with condoms, none used IV drugs and only one had a previous
      history of blood transfusion. CONCLUSIONS: HCV prevalence in female sexual
      workers evaluated was zero. They have few risk factors, sexual transmission of
      this virus is very low and even lower in a population where over 90% of the
      people uses condoms.

PMID- 14716422
TI  - Endoscopic and endosonographic management of pancreatic pseudocyst: a long-term
      follow-up.
AB  - BACKGROUND: The cause of pancreatic cyst were in 72 % due to alcoholism. A
      drainage to pancreatic cyst is very critical for patient with the stomach varices
      patient. The endoscopic ultrasonography(EUS) is a valuable supplement to the
      diagnostic procedure to localise the optimal spot for puncture and to avoid
      haemorrhage due to damage of intra or extra-mural blood vessels. METHODS: The
      drainage was reached by transpapillary endoscopic retrograde pancreatic drainage
      (ERPD), endoscopic cystogastrostomy (ECG) or endoscopic cystoduodenostomy (ECD).
      The case that varices is doubted and If the identification of the cyst is
      difficult the transmural drainage should be carried out under endosonographic
      control. RESULTS: Between 1987 and 2002, 47 patients had been treated for
      panceatic pseudocysts by transmural or transductal drainage EUS-guided drainage
      of a pancreatic pseudocyst or pancreatc abscess was carried out in 5 cases. In
      42patients pancreatic pseudocysts disappeared completely. Six patients suffered a
      relapse 7 to 38 months after removal of the drainage. No more recurrences were
      observed in 22 patients within followed up 5-11 years. In another 6 patients the
      prostheses were renewed because of occlusion or dislocation. Overall 6 patients
      had to undergo surgery, 3 patients due to relapsing cyst, 2 patients because of
      insufficient drainage and one patient because of severe bleeding. There was no
      case of death related to the endoscopic treatment. CONCLUSION: The EUS is a
      valuable supplementation to the diagnostic procedure to localize the optimal spot
      for puncture and to avoid haemorrhage because of damage of intra or extramural
      bloodvessels. Advantages of the endoscopic drainage are minimal invasiveness,
      short period of hospitalization and low costs. These aspects make the endoscopic
      therapy the first choice of treatment of pancreatic pseudocysts.

PMID- 14716423
TI  - [Gastric epithelial polyps (first part)].
AB  - The following is a statistical report regarding gastric polyps:Frequency
      determined through endoscopic examinations was 3.6%. The terms hyperplastic
      polyps and adenomas were used for the classification of epithelial polyps,
      considering the suprafoveal hyperplasias within the hyperplastic polyps, provided
      they were elevated lesions. Out of 2,283 polyps, 1,959 were hyperplastic (86%)
      and 324 were adenomas (14%). When analyzing 780 polyps, 86 (11%) were found to
      have the Nakamura III category. With regard to topography, in an examination of
      2253 polyps, hyperplastic polyps were located as follows: 325 (17%) in the
      antrum, 1402 (73%) in the body and 202 (10%) in the fundus. Adenomas had a
      different distribution: 212 (65%) in the antrum, 100 (31%) in the body and 12
      (4%) in the fundus. Out of 371 hyperplastic polyps examined, 49% were pediculate
      and 51% were sessile; on the contrary, 86 % of adenomas were sessile. The average
      age was 66.2 years in adenoma carriers, 58.5 in those having hyperplastic polyps,
      and 57.4 for suprafoveal hyperplasias. In 287 adenomas, 94.1% of carriers were
      over 40 years old. Out of 92 adenomas examined, 21.7% evidenced adenoma
      metaplasia and 72.8% evidenced metaplasia in adjacent areas. Only 5.5% had no
      metaplasia. In 105 hyperplastic polyps studied, intestinal metaplasia was found:
      16.7% in the polyp and 60% in adjacent areas. No metaplasia was found in the
      remaining 23.3%. Average size of the adenomas was 14 mm and of hyperplastic
      polyps, 11 mm. A total of 195 adenomas were smaller than 10 mm. The percentage of
      malignization in 288 adenomas examined was closely related to their size: 214
      (66%) smaller than 20 mm, had a malignization percentage of 7%; 74 (34%) larger
      than 20 mm, had 51% malignization, and 86.2% malignization was found in adenomas
      of over 40 mm.Global malignization percentage of adenomas was 18%. However, when
      adenomas with high grade dysplasia in the 4.1 category of the Viena
      classification (non-invasive high grade neoplasia) were considered, this
      percentage rose to 26%. Malignization of hyperplastic polyps was 0.8%. When
      gastric acidity was determined using the maximum stimulation method, out of 77
      cases of patients with hyperplastic polyps, 55 (60%) had real achlorhydria, 10
      (18%) hypochlorhydria, 11 (20%) normochlorhydria, and only 1 (4)
      hyperchlorhydria. D.A.B. was 1.97 mEql for hyperplastics and 1.60 mEql for
      adenomas. D.A.M. was 6.05 mEql for hyperplastics and 5.49 mEql for adenomas. Our
      experience as to normal cases showed 2.5 mEqh +/- 1.2 and 22 mEqh +/- 6,
      respectively, for D.A.B and D.A.M.

PMID- 14716424
TI  - [Crohn's disease associated with focal pulmonare lesion].
AB  - 40 year-old male recently diagnosed with Crohn's disease. A routine chest X ray
      showed a round, well defined opacity in right lung field. A chest CT scan
      confirmed the finding and also described bronchiectasis. Patient had no
      respiratory symptoms. He was prescribed with oral sulfasalazine and
      corticosteroids with rapid improvement of intestinal symptoms as well as
      resolution of the pulmonary opacity. We describe the clinical presentation of a
      male newly diagnosed with Crohn's disease who was found to have an asymptomatic
      pulmonary lesion on imaging studies. Pulmonary complications have been previously
      described in inflamatory bowel disease being more common in ulcerative colitis
      than in Crohn's disease; these can involve the lung parenchyma, the
      tracheobronchial tree, and the pleura. The true prevalence and etiology of these
      lesions is currently unknown and are not necessarily associated with bowel
      disease activity. Abnormal pulmonary functions test have been reported during
      inflammatory bowel disease exacerbations, and although pulmonary findings can
      present with a variety of symptoms, subclinical presentations have also been
      described. Pulmonary manifestations are usually steoid-responsive, as was the
      case in our patients.

PMID- 14716425
TI  - [Chylous ascites as evidence of a retroperitoneal lymphoma].
AB  - A case of Chylous Ascites was reported in a 64-year-old male patient who
      underwent a diagnostic laparoscopy, through which its etiology was determined. It
      is a retroperitoneal lymphoma with liver infiltration, an unusual presentation of
      this disease, where diagnosis could be determined.

PMID- 14716426
TI  - [Hereditary hemochromatosis].
AB  - The case of a 43-year-old male is presented, with diagnosed diabetes
      mellitus,heart failure, skin pigmentation, hepatic cirhosis, and hereditary
      hemochromatosis confirmed by liver biopsy. The objective of this publication is
      to have hemochromatosis in mind as a differential diagnosis in a middle-aged
      patient with several pathologies and organs involved.

PMID- 14716427
TI  - [Multiple organ resections for the surgical treatment of locally advanced
      colorectal cancer infiltrating the urinary tract].
AB  - The authors present data on 13 patients operated on for the treatment of locally
      advanced colorectal cancer infiltrating the adjacent parts of the urinary tract.
      Based on prior diagnostic evidences, every surgical intervention has been
      indicated as an expected curative resection. All patients of this study underwent
      a curative resection. The origin of the advanced cancer was in 9 cases the
      sigmoid colon, in 3 cases the rectum and in 1 case the ascending colon. Beside
      the resection of the tumorous colon or rectum, a resection of the urinary bladder
      has been performed in 9, a nephrectomy in 3 and the resection of the ureter in 2
      cases. An additional gynecological resection was made in 4 cases for tumors
      infiltrating the female internal genitals. No mortality and no serious
      complication needing reoperation occurred in these series. Based on their
      experiences of a series of 13 radically operated cases, the authors suggest
      extended multiple organ resection for the treatment of advanced colorectal cancer
      infiltrating the urinary tract.

PMID- 14716428
TI  - [Surgical treatment of neuroendocrine tumours of the pancreas].
AB  - Gastro-entero-pancreatic (GEP) endocrine tumours can originate from various
      pancreatic islet cells, from endocrine cells of the gastric and duodenal mucosa,
      or from APUD cells of neuroectodermal origin in the gastrointestinal tract. They
      are benign when smaller than 2 cm, but larger tumours are generally malignant.
      Surgery is the only method for the curative treatment of GEP tumours. A diagnosed
      and localised tumour is an absolute indication for radical surgery. Conservative
      medical treatment may be indicated only in an inoperable condition, but in this
      case tumour reduction surgery is suggested. In the last 15 years 22 patients with
      pancreatic neuroendocrine tumours were treated without any mortality. Except for
      two of them, the surgical therapy was curative.

PMID- 14716429
TI  - [The occurrence of bronchioloalveolar lung cancer among our patients].
AB  - INTRODUCTION: One of the subtypes of pulmonary adenocarcinoma, bronchioloalveolar
      carcinoma (BAC), is mentioned as the lung cancer of non-smoking women. We have
      studied the clinical characteristics of BAC and its surgical treatment. METHODS
      AND PATIENTS: Between 1992 and 2001, lung resections for BAC were performed on
      101 patients: 55 men and 46 women, average age 59.7 years. Thirty-two of the
      patients were non-smokers, and 69 were active smokers. In 1992 the incidence of
      BAC was 17.5% of all adenocarcinomas, whereas in 2001 it had risen to 51.6%. The
      operations involved 76 lobectomies, 12 pulmonectomies, 11 wedge resections and 2
      explorative thoracotomies. RESULTS: The surgical mortality was 0.9%. The final
      histologic findings revealed that 82.1% of the tumours were in stages I or II,
      with 33.7% of the total in stage I/A. The average 5-year survival was 64.3%.
      Survival for women 75%, was significantly better than that for men, 51%
      (p=0.045). A significant difference was not found in the 5-year survival rate for
      multiple tumours or for BAC cases of different histological types. CONCLUSIONS:
      The incidence of BAC, which occurs relatively frequently among women, and
      exhibits a relatively favourable course, has tended to increase in recent years.
      A majority of these tumours are removed in an early stage. The survival is not
      significantly poorer in the event of multiple tumours.

PMID- 14716430
TI  - [Causes of local recurrence after curative surgery for rectal cancer].
AB  - The rate of local recurrence (LR) has been 20-40% after resective surgery for
      rectal cancer by the traditional - Miles or Dixon - operative technics. The
      authors performed curative resection in 358 patients with rectal cancer in a 10
      year period (01.01.1990 - 31.12.2000) in the Surgical Department of Szeged
      University. Since 01.01.1996 the authors changed this type of surgery for the
      Heald technics (total mesorectal excision - TME - with sharp dissection, using
      the UltraCision device) for the surgical treatment of middle or lower third
      rectal cancer. To compare the results of the two procedures, the authors analysed
      their material in two periods: Period I: 01.01.1991 - 31.12.1992: 62 patients
      operated on with the traditional operative technics; LR 15% within 2 years after
      surgery. Period II: 01.01.1997 - 31.12.1998: 78 patients operated on with the
      Heald technics (TME with sharp dissection); LR 6.4% within 2 years after surgery.
      Based on their results, the authors found that the modern operative technics by
      Heald, used in the second period of the study, was a relevant factor decreasing
      LR from 15% to 6.4%, while the gender, age of the patients, ratio of the
      abdominoperineal extirpation versus anterior resection (APRE/AR) and the free
      margin of more than 3 cm proved to be irrelevant.

PMID- 14716431
TI  - [Results of surgical treatment of pancreatic cancer].
AB  - The aim of this study was to assess the results of the treatment of (255)
      patients with pancreatic cancer in the Department of Surgery, University of
      Szeged, during the time period 1997-2001. METHODS: The age, male/female ratio,
      postoperative morbidity and mortality were discussed. RESULTS: The resecability
      rate was 17.3% (44/255 patients). The mortality rate was 2.3% (1/44 patients)
      after radical operations and 12.1% (15/124 patients) after the palliative
      procedures. Localization and UICC staging after pancreatic tumors were analyzed.
      CONCLUSIONS: In spite of the improvement of the new diagnostic methods, the
      proportion of patients undergoing radical surgery has not been increased in this
      period. Palliative surgical procedures are indicated in the case of advanced
      tumor stage. Choledochojejunostomy with Roux-Y loop offers the best results for
      the treatment of biliary obstruction. The role of endoscopic stenting is very
      questionable and the increased rate of postoperative biliary infections indicates
      that this procedure should be avoided in the preoperative treatment of patients
      who are suitable for potentially curative operation.

PMID- 14716432
TI  - [Surgical treatment of gastric cancer: new methods and longstanding
      difficulties].
AB  - The incidence of gastric carcinoma has been declining and the same tendency is
      observed in Hungary. The five-year survival rate has been improved due to the
      fewer postoperative deaths and the more radical operations (e.g. extended
      lymphadenectomies). METHODS: The authors analyzed the clinical data of 183
      patients with gastric carcinoma. Age, sex, histology reports, TNM staging and the
      surgical interventions are presented. RESULTS: Potentially curative resection
      could be performed in about half of the patients (92/182). A large proportion of
      the patients belonged to the locally advanced cancer group (112/182). The ratio
      of the different TNM stages remained the same year by year in the investigated
      period despite the improving endoscopic facilities. CONCLUSION: Early diagnosis
      of gastric cancer is crucial and continuous effort should be made by the
      surgeons, the gastroenterologist and the general practitioners to identify high
      risk patients with the use of new, sensitive screening methods.

PMID- 14716433
TI  - [Surgical and endoscopic management of bile duct cancer].
AB  - There is still considerable controversy regarding the value of surgical versus
      nonsurgical treatment for bile duct cancer. Therapeutic modalities vary from
      total hepatectomy and liver transplantation to percutaneous or endoscopic stent
      insertion. The aim of this study was to assess the results of the treatment of
      118 patients presented with bile duct cancer in the Department of Surgery,
      University of Szeged, during the time period 1990-2002. METHODS: The age,
      male/female ratio, postoperative morbidity and mortality were analyzed. RESULTS:
      The resectability rate was 18% (21/118). The mortality rate was 23.8% (5/21)
      after radical operations and 7% or 12.5% after the palliative procedures. 67
      patients had palliative surgery following unsuccessful or recurrent jaundice
      after non-surgical palliation. The previously applied palliative methods have
      been transpapillary stenting, endoscopic pig-tail drainage, percutaneous
      transhepatic drainage or dilatation. CONCLUSIONS: Palliative surgery for jaundice
      caused by extrahepatic bile duct cancer is justified in cases with an
      unsuccessful attempt for endoscopic stenting or occlusion of endoscopically
      placed endoprothesis. Bilio-enteric bypass with a Roux-Y jejunal loop is superior
      than external drainage respecting desicterization, postoperative recovery,
      mortality, complication rate and quality of life.

PMID- 14716434
TI  - [The role of laparoscopy in the surgical treatment of colorectal cancer. Initial
      results].
AB  - The authors have carried out laparoscopically assisted abdomino-perineal rectal
      resections on a selected group of 8 patients during the past two years. The
      laparoscopic technique was not accompanied by any complications, while the
      patients enjoyed the benefits of the procedure. The bowel function of the
      patients were restored on the 2nd to 3rd day, the mean length of the hospital
      stay was 8.3 days. On the basis of their own favourable initial experience and
      recent literature data, the authors discuss the benefits, disadvantages and
      pitfalls of the laparoscopically assisted technique for surgical treatment of
      colorectal cancer. The problematics of oncological radicality is analysed.

PMID- 14716435
TI  - [Palliation of inoperable esophageal tumor with endoscopic intubation].
AB  - RATIONALE: Access to expensive equipment and costly self-expanding metal
      endoprostheses is limited in some regions where unresectable esophageal cancer is
      not infrequent. The aim of this study was to review the long-term results of
      palliation of malignant esophageal obstruction using low-priced conventional
      plastic stents. PATIENTS AND METHODS: 103 patients with dysphagia due to
      inoperable esophageal cancer underwent esophageal intubation under endoscopic
      control alone, without general anesthesia, by the pulsion method. Stents mounted
      on their delivery device were inserted over an endoscopically placed guide wire.
      RESULTS: Improvement in swallowing was seen in 100%. Dysphagia scores have
      improved from 3.64+/-0.21 to 1.08+/-0.17. Major early procedure-related morbidity
      was low (0.6%), with 1 intramural perforation and no transmural perforation at
      all. Minimal mucosal bleeding was seen with 48 cases (46.6%). Procedure-related
      mortality was 0%. Late procedure-related complications requiring further
      endoscopic procedures occurred in 13.5% (tube occlusion: 8.7%, tube dislocation:
      4.8%). Our 7 day mortality was 0% and 5 patients had died within 30 days, usually
      from the disease itself. Those surviving the procedure (>7 days) had a mean
      survival of 209 days. CONCLUSION: Esophageal plastic stents can be accurately and
      safely placed under direct endoscopic control with lower costs. Therefore,
      endoscopic intubation remains a useful palliative treatment for patients with
      unresectable carcinoma of the esophagus.

PMID- 14716436
TI  - [Surgery of benign liver tumors: indications for treatment. Personal experience
      and review of the literature].
AB  - BACKGROUND AND AIMS: Our aim is to give an audit of our experience over the past
      two decades in the form of a retrospective study. PATIENTS/METHODS: Between 1
      January, 1982 and 15 December, 2001, 133 patients with benign liver tumor
      (adenoma: 22, focal nodular hyperplasia: 27, hemangioma: 83, lipoma: 1) were
      treated. A total of 113 patients underwent surgery, while 20 asymptomatic cases
      were merely observed. The mean age, the female/male ratio and the size of the
      tumor in the adenoma cases were 38.3+/-10.2 years, 20/2 and 7.7+/-2.4 cm, while
      for focal nodular hyperplasia they were 39.5+/-12.4, 24/3 and 6.3+/-2.7 cm, and
      for hemangioma 49.01+/-10.7, 62/21 and 6.5+/-3.6 cm. The results were compared
      and analyzed statistically. RESULTS: Enucleation was performed in 53.1% of the
      patients, non-anatomical resection in 24.8%, segmentectomy in 6.2%, lobectomy in
      4.4%, extended lobectomy in 1.8%, stitching in 5.3%, exploration in 3.5% and
      liver transplantation in 0.9%. The overall 30-day postoperative mortality was
      0.9% (1/113). Minor or major complications occurred in a total of 27.4%.
      CONCLUSIONS: Patients with asymptomatic focal nodular hyperplasia or hemangiomas
      must be excluded from surgery. Surgery is indicated only when growth or severe
      complaints are observed. Adenomas must be resected because of the precancerous
      behavior and the danger of bleeding from a rupture.

PMID- 14716437
TI  - [Prognostic significance of intrapulmonary metastases in cases of surgically
      treated lung cancer].
AB  - OBJECTIVE: The aim of this retrospective study was to establish the prognosis in
      lung tumour cases in which resection was followed by synchronous or metachronous
      intrapulmonary metastasis. METHODS: Between 1990 and 1999, 857 patients were
      operated on for primary lung cancer. Intrapulmonary metastases were observed in
      21 patients. 11 cases were in stage III/B (on the basis of T4), and 10 were in
      stage IV (on the basis of M1). The histologic distribution of the primary tumours
      was 7 squamous cell carcinomas, 11 adenocarcinomas, 2 large cell carcinomas and 1
      carcinoid. In 8 patients, histology demonstrated N1 or N2 lymph node metastasis.
      In 4 cases, there were more than one metastases. RESULTS: The 5-year survival was
      21%, and the mean survival time (MST) was 29.5 months. For both the 5-year
      survival rate and MST, there was significant difference between the lymph node
      negative (N0) and lymph node positive (N1/N2) patients (N-: 30.7%, N+: 0%,
      p=0.017, MST: N-: 38.3 months, N+: 10.5 months, p=0.014), according to the stage
      (III/B: 30%, IV: 11.1%, p=0.025, III/B: 40.1 months, IV: 17.8 months, p=0.04) and
      the number of metastases (1 metastasis: 26.6%, more than 1 metastasis: 0%,
      p=0.036, 1 metastasis: 35.2 months, more than 1 metastasis: 8.5 months, p=0.045).
      No significant difference was detected on the basis of histological type,
      pleural, vascular and lymphatic invasion. In patients where 1 metastasis was
      found within one lobe and there were no lymph node metastases, the 5-year
      survival rate was 42.8% and MST was 49 months. The complication rate was 28.5%
      and the 30-day mortality was 4.7% (1 patient). Reoperation was performed in 1
      case, for thoracic wall haematoma. CONCLUSION: Primary lung tumours giving
      intrapulmonary metastases, under certain conditions (lymph node negativity, 1
      metastasis in the same lobe), can be operated on with good survival
      possibilities.

PMID- 14716438
TI  - [Improving results of the surgical treatment of rectal cancer in the Surgical
      Department of County Hospital, Szekszard].
AB  - The authors present that 247 elective rectal operations were performed between 1
      January, 1996 and 31 December, 2001 in their surgical department. The examined 6
      years were divided into a 4-year and a 2-year period. 148 operations were
      performed in the first and 99 in the second period. Beside personal changes,
      methodical and technical modifications were introduced in the second period.
      Distribution of age and sex was similar, and the groups were comparable. The
      early postoperative mortality rate decreased from 9% to 4% during the examined
      time. Due to the double stapling technique, the rate of anterior rectal
      resections has increased from 40% to 69%, and the rate of abdomino-perineal
      rectal extirpation has decreased from 43% to 23%. Considerable difference was
      found in the rate of palliative stoma-creation operations, since the 16%
      decreased to 8% in the second period, so the quality of life of patients has
      improved. The operative time, the hospital stay of the patients and the rate of
      operations with blood transfusion decreased. The different types of postoperative
      infections decreased due to the new methods.

PMID- 14716439
TI  - Topical 3% diclofenac in 2.5% hyaluronan gel for the treatment of actinic
      keratoses.
AB  - Actinic Keratoses (AKs) are epidermal skin lesions that have the potential to
      develop into squamous cell carcinoma. Many of the treatment options available can
      cause discomfort, pain or skin irritation. Topical 3% diclofenac in 2.5%
      hyaluronan gel (Solaraze, Bioglan Pharma) is a relatively new treatment that has
      been shown to be effective and well tolerated for the treatment of AKs.

PMID- 14716440
TI  - Laser treatment of scars.
AB  - Over the past decade, refinements in laser technology as well as advances in
      laser techniques have enabled dermatologic surgeons to define the most
      appropriate lasers to use for different scar types without the adverse sequelae
      and recurrence rates noted with older surgical revision techniques and continuous
      wave laser systems.

PMID- 14716449
TI  - Three-dimensional reconstructed images using multidetector computed tomography in
      evaluation of the biliary tract.
AB  - The recent development of multidetector computed tomography (MDCT) and the
      parallel escalation in the capabilities of the workstation allow the use of high
      quality multiplanar and three-dimensional reconstruction images. As a noninvasive
      technique, MDCT dedicated to the biliary tract represents an alternative to
      magnetic resonance cholangiography. The usefulness of three-dimensional
      reconstructed images using MDCT in evaluating biliary tract abnormality is
      illustrated.

PMID- 14716451
TI  - Liver tumors: evaluation with contrast-enhanced ultrasound.
AB  - The development and clinical introduction of microbubble contrast agents has had
      a particular impact on the detection and differential diagnosis of liver tumors.
      The first approach widely employed made use of high-transmission power
      ultrasound, which destroyed the microbubbles in the process of imaging them. It
      is particularly successful for those agents that have a liver-specific post
      vascular phase because, like liver-specific agents used in other imaging
      modalities such as magnetic resonance imaging and nuclear medicine, malignancies
      do not retain the contrast, so they stand out with very high conspicuity. Used
      this way with color Doppler or variants of it, more subcentimeter lesions can be
      demonstrated with ultrasound than with computed tomography. However, the
      destructive nature of this approach meant that continuous real-time scanning was
      impossible. Two developments allowed this to be redressed: new classes of
      microbubbles with perfluoro gasses instead of air and the invention of multipulse
      scanning modes that are sensitive to the nonlinear (harmonic) responses of the
      microbubbles and suppresses tissue signals. This low-power approach is now used
      almost exclusively, and it has the advantage of displaying the arterial phase of
      blood supply to a mass and a later phase when the bubbles are trapped in the
      sinusoids so that the vascular volume of the tissue is depicted. Malignancies
      typically show a low signal intensity in this phase, regardless of whether they
      are hyper- or hypovascular in terms of their arterial supply. This allows them to
      be detected with high sensitivity and much more easily than the destructive modes
      allowed. In addition, the arterial supply that can be now depicted in real time
      has characteristics that allow most benign masses to be distinguished from each
      other and from malignancies, thus improving specificity. Microbubbles also can be
      used as tracers to provide functional information that can detect occult
      metastases and cirrhosis noninvasively.

PMID- 14716452
TI  - Congenital absence of the portal vein associated with focal nodular hyperplasia
      in the liver in an adult woman: imaging and review of the literature.
AB  - We present a new case of congenital absence of the portal vein and focal nodular
      hyperplasia in the liver without additional congenital anomalies. Ultrasound,
      computed tomography, magnetic resonance imaging, and angiography depicted the
      splenic vein and the superior mesenteric vein joining and entering into the
      inferior vena cava without passing through the liver. The features of this
      patient and the 30 previously reported cases are reviewed.

PMID- 14716453
TI  - Spontaneous subacute intratumoral hemorrhage of hepatic cavernous hemangioma.
AB  - We report a case of giant hepatic cavernous hemangioma associated with
      spontaneous subacute intratumoral hemorrhage. Magnetic resonance imaging showed
      an oval, homogeneous, high-intensity lesion with a low-intensity rim in the
      original high-intensity tumor on T2-weighted images. On T1-weighted images, this
      oval lesion showed heterogeneous high intensity with peripheral higher intensity.
      The histologic specimen confirmed hepatic hemangioma with intratumoral
      hemorrhage.

PMID- 14716454
TI  - Detection of reflux esophagitis on double-contrast esophagrams and endoscopy
      using the histologic findings as the gold standard.
AB  - The purpose of our study was to determine the accuracy of double-contrast barium
      studies and endoscopy for detecting reflux esophagitis, using the endoscopic
      biopsy findings as the gold standard. A review of radiology, endoscopy, and
      pathology files showed 37 patients with reflux symptoms who underwent double
      contrast barium studies and endoscopy with biopsy specimens from the esophagus.
      The radiographic images were reviewed in a blinded fashion and correlated with
      the endoscopic and histologic findings to determine the radiographic and
      endoscopic accuracies for detecting reflux esophagitis, using the endoscopic
      biopsy specimens as the gold standard. Double-contrast barium studies and
      endoscopy had low but comparable accuracies for detecting reflux esophagitis,
      with sensitivities of 35% and 39%, specificities of 79% and 71%, positive
      predictive values of 73% and 69%, and negative predictive values of 42% and 41%,
      respectively. When mucosa granularity was evaluated as an individual sign of
      esophagitis on double-contrast studies, this finding had a sensitivity of 35%, a
      specificity of 93%, a positive predictive value of 89%, and a negative predictive
      value of 46% for detecting reflux esophagitis. Our experience suggests that
      double-contrast barium studies and endoscopy have limited ability to detect
      reflux esophagitis, in particular mild esophagitis, when using the histologic
      findings as the gold standard. When radiographic abnormalities are detected,
      however, mucosal granularity is the single best sign of reflux esophagitis on
      double-contrast studies.

PMID- 14716455
TI  - Dark-lumen MR colonography.
AB  - Magnetic resonance colonography (MRC) has been shown to be an appropriate
      diagnostic tool for the detection of colorectal pathologies. Recently, dark-lumen
      MRC has been introduced. This technique is based on the acquisition of a T1
      weighted sequence after the administration of water enema and the intravenous
      administration of paramagnetic contrast. This report describes the underlying
      techniques of dark-lumen MRC concerning data acquisition and image
      interpretation. Furthermore, it points out the advantages of this approach as
      compared with conventional endoscopy or other MR methods. Possible improvements
      in the future such as the implementation of fecal tagging strategies to avoid
      bowel cleansing are discussed.

PMID- 14716465
TI  - Yeast cell-surface display--applications of molecular display.
AB  - In a cell-surface engineering system established using the yeast Saccharomyces
      cerevisiae, novel, so-called arming yeasts are constructed that are armed with
      biocatalysts in the form of enzymes, functional proteins, antibodies, and
      combinatorial protein libraries. Among the many advantages of the system, in
      which proteins are genetically displayed on the cell surface, are easy
      reproduction of the displayed biocatalysts and easy separation of product from
      catalyst. As proteins and peptides of various kinds can be displayed on the yeast
      cell surface, the system is expected to allow the preparation of tailor-made
      functional proteins. With its ability to express many of the functional proteins
      necessary for post-translational modification and in a range of different sizes,
      the yeast-based molecular display system appears uniquely useful among the
      various display systems so far developed. Capable of conferring novel additional
      abilities upon living cells, cell-surface engineering heralds a new era of
      combinatorial bioengineering in the field of biotechnology. This mini-review
      describes molecular display using yeast and its various applications.

PMID- 14716466
TI  - Chirality of pollutants--effects on metabolism and fate.
AB  - In most cases, enantiomers of chiral compounds behave differently in biochemical
      processes. Therefore, the effects and the environmental fate of the enantiomers
      of chiral pollutants need to be investigated separately. In this review, the
      different fates of the enantiomers of chiral phenoxyalkanoic acid herbicides,
      acetamides, organochlorines, and linear alkylbenzenesulfonates are discussed. The
      focus lies on biological degradation, which may be enantioselective, in contrast
      to non-biotic conversions. The data show that it is difficult to predict which
      enantiomer may be enriched and that accumulation of an enantiomer is dependent on
      the environmental system, the species, and the organ. Racemization and
      enantiomerization processes occur and make interpretation of the data even more
      complex. Enantioselective degradation implies that the enzymes involved in the
      conversion of such compounds are able to differentiate between the enantiomers.
      "Enzyme pairs" have evolved which exhibit almost identical overall folding. Only
      subtle differences in their active site determine their enantioselectivities. At
      the other extreme, there are examples of non-homologous "enzyme pairs" that have
      developed through convergent evolution to enantioselectively turn over the
      enantiomers of a chiral compound. For a better understanding of enantioselective
      reactions, more detailed studies of enzymes involved in enantioselective
      degradation need to be performed.

PMID- 14716467
TI  - Microbial P450 enzymes in biotechnology.
AB  - Oxidations are key reactions in chemical syntheses. Biooxidations using
      fermentation processes have already conquered some niches in industrial oxidation
      processes since they allow the introduction of oxygen into non-activated carbon
      atoms in a sterically and optically selective manner that is difficult or
      impossible to achieve by synthetic organic chemistry. Biooxidation using isolated
      enzymes is limited to oxidases and dehydrogenases. Surprisingly, cytochrome P450
      monooxygenases have scarcely been studied for use in biooxidations, although they
      are one of the largest known superfamilies of enzyme proteins. Their gene
      sequences have been identified in various organisms such as humans, bacteria,
      algae, fungi, and plants. The reactions catalyzed by P450s are quite diverse and
      range from biosynthetic pathways (e.g. those of animal hormones and secondary
      plant metabolites) to the activation or biodegradation of hydrophobic xenobiotic
      compounds (e.g. those of various drugs in the liver of higher animals). From a
      practical point of view, the great potential of P450s is limited by their
      functional complexity, low activity, and limited stability. In addition, P450
      catalyzed reactions require a constant supply of NAD(P)H which makes continuous
      cell-free processes very expensive. Quite recently, several groups have started
      to investigate cost-efficient ways that could allow the continuous supply of
      electrons to the heme iron. These include, for example, the use of electron
      mediators, direct electron supply from electrodes, and enzymatic approaches. In
      addition, methods of protein design and directed evolution have been applied in
      an attempt to enhance the activity of the enzymes and improve their selectivity.
      The promising application of bacterial P450s as catalyzing agents in biocatalytic
      reactions and recent progress made in this field are both covered in this review.

PMID- 14716468
TI  - Evaluation of bacterial strategies to promote the bioavailability of polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbon (PAHs)-degrading bacteria may enhance the
      bioavailability of PAHs by excreting biosurfactants, by production of
      extracellular polymeric substances, or by forming biofilms. We tested these
      hypotheses in pure cultures of PAHs-degrading bacterial strains. Most of the
      strains did not substantially reduce the surface tension when grown on PAHs in
      liquid shaken cultures. Thus, pseudo-solubilization of PAHs in biosurfactant
      micelles seems not to be a general strategy for these isolates to enhance PAHs
      bioavailability. Three semi-colloid Sphingomonas polysaccharides all increased
      the solubility of PAHs (Gellan 1.3- to 5.4-fold, Welan 1.8- to 6.0-fold and
      Rhamsan 2.4- to 9.0-fold). The increases were most pronounced for the more
      hydrophobic PAHs. The polysaccharide-sorbed PAHs were bioavailable.
      Mineralization rates of 9-[14C]-phenanthrene and 3-[14C]-fluoranthene by
      Sphingobium EPA505, were similar with and without sphingans, indicating that mass
      transfer rates from PAHs crystals to the bulk liquid were unaffected by the
      polysaccharides. Biofilm formation on PAHs crystals may favor the diffusive mass
      transfer of PAHs from crystals to the bacterial cells. A majority of the PAHs
      degraders tested formed biofilms in microtiter wells coated with PAHs crystals.
      For strains capable of growing on different PAHs; the more soluble the PAHs, the
      lower the percentage of cells attached. Biofilm formation on PAHs-sources was the
      predominant mechanism among the tested bacteria to overcome mass transfer
      limitations when growing on poorly soluble PAHs.

PMID- 14716469
TI  - Bioavailability of pentachlorophenol to acclimatised bacteria under batch and
      flow-through conditions.
AB  - Biodegradation of organic contaminants in multi-phase systems, such as soils and
      aquifers, is often limited by the extent and the rate of contaminant sorption
      onto the solid matrix. However, information about biodegradation in complex
      matrices is largely limited to studies of closed systems under batch conditions
      in which potential bioavailability is characterised by the aqueous-phase
      concentration of a contaminant. There is little knowledge regarding the influence
      of flow-through conditions on the availability of contaminants to microbes
      (contaminant bioavailability). Thus, the aim of this study was to assess and
      compare contaminant bioavailability, in the presence of a sorptive medium, under
      both batch and flow-through conditions. Accordingly, experiments were designed in
      which pentachlorophenol (PCP) was introduced into a mixture of inoculated silica
      sand and a PCP-retaining resin, under either batch or flow-through (columns)
      conditions. The results indicated that an increase in the amount of resin (0.1
      0.2 g) clearly lowered PCP availability to microbes after 170 h under batch
      conditions (30 and 45% respectively); whereas, the initial decrease in
      bioavailability observed under flow-through conditions (45 and 70% respectively)
      was reversed and no longer observable after 170 h. This increase in PCP
      availability was linked to an improvement in the contaminant biodegradation
      capacity from 0.03 to 0.13 mg x l(-1) x h(-1) over 200 h.

PMID- 14716471
TI  - A mini-review of mass spectrometry using high-performance FTICR-MS methods.
AB  - Structural characterization of macromolecules is currently delivering new
      insights into the behavior of individual molecules or molecular ensembles.
      Technological advances have made it possible to examine smaller and smaller
      amounts (down to single molecules) of larger and larger molecular systems. Mass
      spectrometry in particular is capable of the detailed study of extremely small
      quantities (down to a single molecule) of very large (biological) molecules. The
      advent of new ionization techniques such as electrospray and matrix-assisted
      laser desorption are mainly responsible for these advances. As a result, mass
      spectrometry has evolved into an enabling discipline that plays an increasingly
      important role in combinatorial chemistry, polymer science, biochemistry,
      medicine, environmental and marine science, and archaeology and conservation
      science. This paper will review a selection of methodological developments in the
      field of high-performance Fourier transform ion cyclotron resonance mass
      spectrometry for structural analysis of these macromolecules.

PMID- 14716472
TI  - Effects of beta-adrenoceptor blockade on components of human decision-making.
AB  - RATIONALE: Converging evidence from studies with neurological patients and brain
      imaging studies with healthy volunteers suggests that the capacity to make
      choices between actions associated with probabilistic rewards and punishments
      depends upon a network of cortico-limbic systems including the orbitofrontal
      cortex, cingulate cortex, amygdala and striatum. The involvement of such
      structures highlights the emotional aspects of decision-making and suggests that
      decision-making may be sensitive to manipulations of the catecholamine systems
      that innervate these structures. In this study, we investigated the possible role
      of noradrenaline (NA). OBJECTIVE: We examined the effects of a single oral 80 mg
      dose of the beta-adrenoceptor blocker, propranolol, on the decision-making of
      healthy volunteers in a double-blind, placebo-controlled, between-subjects
      design. METHODS: Seventeen volunteers ingested a placebo while 15 volunteers
      ingested propranolol. Visual analogue scales, and self-reported positive and
      negative ratings, were used to assess subjective changes and mood. Vital signs
      were also monitored. Seventy-five minutes after treatment, volunteers were asked
      to make a series of choices between two simultaneously presented gambles,
      differing in the magnitude of possible gains (i.e. reward), the magnitude of
      possible losses (i.e. punishment), and the probabilities with which these
      outcomes were delivered. Volunteers also chose between gambles probing identified
      non-cognitive biases in human decision-making, namely, risk-aversion when
      choosing between gains and risk-seeking when choosing between losses. RESULTS:
      Propranolol treatment did not result in gross changes in subjective state or mood
      in comparison to placebo, but did slow heart rate significantly. Propranolol
      produced a selective change in volunteers' decision-making; namely, it
      significantly reduced the discrimination between large and small possible losses
      when the probability of winning was relatively low and the probability of losing
      was high. CONCLUSIONS: These results suggest that NA modulates the processing of
      punishment signals when choosing between probabilistic rewards and punishments
      under conditions of increased arousal.

PMID- 14716473
TI  - Utilization of aminoaromatic acids by a methanogenic enrichment culture and by a
      novel Citrobacter freundii strain.
AB  - Following incubation of mesophilic methanogenic floccular sludge from a lab-scale
      upflow anaerobic sludge bed reactor used to treat cattle manure wastewater, a
      stable 5-aminosalicylate-degrading enrichment culture was obtained. Subsequently,
      a Citrobacter freundii strain, WA1, was isolated from the 5-aminosalicylate
      degrading methanogenic consortium. The methanogenic enrichment culture degraded 5
      aminosalicylate completely to CH4, CO2 and NH4+, while C. freundii strain WA1
      reduced 5-aminosalicylate with simultaneous deamination to 2-hydroxybenzyl
      alcohol during anaerobic growth with electron donors such as pyruvate, glucose or
      serine. When grown on pyruvate, C. freundii WA1 converted 3-aminobenzoate to
      benzyl alcohol and also reduced benzaldehyde to benzyl alcohol. Pyruvate was
      fermented to acetate, CO2, H2 and small amounts of lactate, succinate and
      formate. Less lactate (30%) was produced from pyruvate when C. freundii WA1 grew
      with 5-aminosalicylate as co-substrate.

PMID- 14716474
TI  - Acute fractures of medial and lateral great toe sesamoids in an athlete.
AB  - We report a case of acute fracture of both sesamoids of the great toe in an
      athlete. The fractures healed uneventfully after non-surgical treatment.

PMID- 14716475
TI  - The 2003 European heat wave.

PMID- 14716476
TI  - The epidemiologist in the intensive care unit.

PMID- 14716477
TI  - Supply and demand of organs for donation.

PMID- 14716478
TI  - Lessons from a heat wave.

PMID- 14716479
TI  - [Health care quality: medication and prevention in patients with and without
      coronary heart disease].
AB  - BACKGROUND AND PURPOSE: Next to noninvasive-recently also invasive-diagnostics,
      ambulant care in patients with coronary heart disease (CHD) should focus on
      optimal medication and prevention. The aim of this study was to evaluate actual
      health care quality concerning drug prescription and preventive care in patients
      with CHD. PATIENTS AND METHODS: This prospective study was conducted from March
      1999 to February 2002 at the University Hospital Bergmannsheil, Bochum, Germany.
      300 patients admitted with a suspected CHD and without previous coronary
      angiography or myocardial infarction were enrolled. Diagnostic and therapeutic
      regimen complied with actual guidelines. 248 patients (82.7%) including 116
      patients with angiographically confirmed CHD were examined after 1 year. RESULTS:
      On follow-up, only 70.9% of patients with confirmed CHD received a beta-blocker,
      83.6% were treated with platelet aggregation inhibitors. Body mass index, portion
      of overweight patients, and HbA(1c) in patients with diabetes did not change
      during observation. After 1 year, 48.0% of the subjects had a systolic blood
      pressure > 139 mmHg, in 22.6% diastolic pressure level was > 89 mmHg. Blood level
      of low-density cholesterol exceeded the recommended range in 57.0% of the cases
      observed with equally high portion of inadequately treated patients in the group
      with confirmed CHD and in the group without CHD. CONCLUSION: Drug therapy,
      primary and secondary prevention in the observed subjects were fairly poor.
      Remarkable deficits in health care quality became obvious. There is no lack in
      availability of evaluated, effective and efficient measures. Thus, physicians'
      efforts to implement evidence-based guidelines into clinical practice have to be
      strengthened.

PMID- 14716480
TI  - [Regulation of hepatobiliary transporters in cholestatic liver disease].
AB  - Bile formation essentially depends on hepatobiliary organic anion transporters,
      which are exclusively localized either to the sinusoidal or canalicular membrane.
      Cloning of their genes has elucidated the pathophysiology of both hereditary and
      acquired forms of cholestasis. The regulation of these transporter genes occurs
      either by ubiquitous nuclear hormone receptors, which are activated by ligands
      including xenobiotics and bile acids, or by hepatocyte-specific trans-activators.
      Proinflammatory cytokines such as tumor necrosis factor alpha and interleukin
      1beta represent additional mediators. Understanding of these regulatory pathways
      represents a mandatory prerequisite for any future therapeutic intervention in
      acute or chronic liver diseases.

PMID- 14716481
TI  - [Current aspects of electrical cardioversion in patients with persistent atrial
      fibrillation].
AB  - BACKGROUND: Results of recent studies suggest new aspects in the concept of the
      management of patients with atrial fibrillation. Current trials comparing rhythm
      control by cardioversion followed by antiarrhythmic drug therapy with heart rate
      control only showed that rhythm control was not superior to rate control. SPECIAL
      ASPECTS OF ELECTRICAL CARDIOVERSION: However, some subgroups of patients with
      frequent or severe symptoms and younger patients with structurally normal hearts
      may benefit from cardioversion. In patients with persistent atrial fibrillation,
      sinus rhythm can be restored in approximately 90% by direct current transthoracic
      cardioversion. Transthoracic cardioversion is effective and safe, if
      anticoagulation is used. Attempts have been made to improve the success rate by
      new techniques. However, definition of subgroups and stabilization of sinus
      rhythm are ongoing issues of debate.

PMID- 14716482
TI  - [When stroke strikes--after-care and rehabilitation].

PMID- 14716483
TI  - [Infectious diseases-part I: epidemiology].
AB  - The outstanding issue regarding recent trends in the epidemiology of infectious
      diseases is the epidemic occurrence of severe acute respiratory syndrome (SARS)
      in 2003. SARS is caused by a novel coronavirus, presumably originating from wild
      cats. This new agent was rapidly identified and characterized, the outbreak was
      terminated in early summer 2003 after implementation of strict infectious control
      measures. Especially the high rate of complications and nosocomial infections has
      caused severe public health problems in China and Canada. The number of persons
      infected with HIV is still rising rapidly globally. New regions with rapid spread
      include the countries of the former Soviet Union in East Europe and Central Asia.
      The introduction of modern antiretroviral therapy in countries with high
      prevalence is making slow progress, with no visible impact on transmission
      dynamics so far. The WHO has implemented a number of programs to eradicate or
      eliminate targeted infectious diseases. Polio eradication and elimination of
      neonatal tetanus are making slow progress, obstacles to the control of these
      diseases are ongoing armed conflicts in regions with high prevalence and under
      financing of programs. Lack of funding is especially obvious regarding programs
      for the control and therapy of malarial infections. The numbers of patients newly
      identified with new variant Creutzfeldt-Jakob disease are not rising, but rather
      constant or even declining, making a large epidemic of vCJD unlikely.

PMID- 14716484
TI  - [Pulmonary lymphangioleiomyomatosis as a rare cause of recurrent spontaneous
      pneumothorax].
AB  - BACKGROUND: Pulmonary lymphangioleiomyomatosis is a rare disease that occurs
      mainly in women of reproductive age. The clinical characteristics include
      recurrent spontaneous pneumothorax and progressive dyspnea. The features of chest
      computed tomography are nearly pathognomonic with the detection of bilateral thin
      walled cysts. CASE REPORT: A 32-year-old female presented with sudden-onset right
      sided chest pain, which aggravated during inspiration, dyspnea at exertion, and
      cough. She had a history of bilateral recurrent spontaneous pneumothorax.
      Physical examination showed reduced pulmonary sounds on the right side. Chest X
      ray confirmed the diagnosis of recurrent right-sided pneumothorax. Computed
      tomography showed multiple bilateral bullae. Video-assisted pleurectomy, bulla
      resection, and bulla coagulation were performed. The diagnosis of pulmonary
      lymphangioleiomyomatosis was confirmed by pulmonary biopsy. After pleurectomy,
      the patient remained symptom-free without recurrent pneumothorax. CONCLUSION:
      Pulmonary lymphangioleiomyomatosis is a rare cause of recurrent pneumothorax and
      should be considered a differential diagnosis, especially in young women with
      diffuse bilateral bullous emphysema or tuberous sclerosis.

PMID- 14716485
TI  - [Funicular myelosis].

PMID- 14716486
TI  - [DRG case references].

PMID- 14716489
TI  - SGK1 increases Na,K-ATP cell-surface expression and function in Xenopus laevis
      oocytes.
AB  - The Na(+)-retaining hormone aldosterone increases the cell-surface expression of
      the luminal epithelial sodium channel (ENaC) and the basolateral Na(+) pump (Na,K
      ATPase) in aldosterone-sensitive distal nephron cells in a coordinated fashion.
      To address the question of whether aldosterone-induced serum and glucocorticoid
      regulated kinase-1 (SGK1) might be involved in mediating this regulation of Na,K
      ATPase subcellular localization, similar to that of the epithelial Na(+) channel
      (ENaC), we co-expressed the Na,K-ATPase (rat alpha 1- and Xenopus laevis beta 1
      subunits) and Xenopus SGK1 in Xenopus oocytes. Measurements of the Na(+) pump
      current showed that wild-type SGK1 increases the function of exogenous Na,K
      ATPase at the surface of Xenopus oocytes. This appeared to be secondary to an
      increase in Na,K-ATPase cell-surface expression as visualized by Western blotting
      of surface-biotinylated proteins. In contrast, the functional surface expression
      of two other exogenous transporters, the heterodimeric amino acid transporter
      LAT1-4F2hc and the Na(+)/phosphate cotransporter NaPi-IIa, was not increased by
      SGK1 co-expression. The total pool of exogenous Na,K-ATPase was increased by the
      co-expression of SGK1, and similarly also by ENaC co-expression. This latter
      effect depended on the [Na(+)] of the buffer and was not additive to that of
      SGK1. When the total Na,K-ATPase was increased by ENaC co-expression, SGK1 still
      increased Na,K-ATPase cell-surface expression. These observations in Xenopus
      oocytes suggest the possibility that SGK1 induction and/or activation could
      participate in the coordinated regulation of Na,K-ATPase and ENaC cell-surface
      expression in the aldosterone-sensitive distal nephron.

PMID- 14716490
TI  - The transoocyte voltage clamp: a non-invasive technique for electrophysiological
      experiments with Xenopus laevis oocytes.
AB  - We developed a non-invasive technique for electrophysiological investigations of
      ion transport proteins endogenously or heterologously expressed in Xenopus laevis
      oocytes. We named this technique the transoocyte voltage clamp (TOVC). Whereas in
      the classical two-microelectrode voltage-clamp (TEVC) technique, the oocyte is
      impaled with two glass microelectrodes, we mount the egg in a modified Ussing
      chamber as used for transepithelial electrophysiological studies. The oocyte is
      introduced in a container that is positioned between the two chamber halves.
      Proper fixation of the oocyte in the aperture of the container is accomplished
      under a stereo binocular microscope and the electrical seal between the oocyte
      and the container is achieved with silicon grease. The new method allows
      measurement of transoocyte currents and conductances as well as the recording of
      membrane impedance and the fluctuation analysis of ion currents. We studied a K+
      channel that resembles the inward rectifier K+ channel endogenously expressed in
      Xenopus laevis oocytes. K+ currents were obtained by exposing one side of the
      oocyte to K(+)-containing solutions and by the application of different voltages.
      Adding Cs+ and Ba2+ inhibited these currents. The analysis of the fluctuation in
      current demonstrated a Lorentzian component in the power density spectrum. With
      the transoocyte voltage clamped to zero, the corner frequency (fc) was 61+/-1.7
      Hz. Imposed positive transoocyte potentials caused a downward shift of fc. These
      findings are consistent with previous data obtained using the TEVC technique, and
      extend the characterization of the channel with kinetic data obtained from noise
      analysis.

PMID- 14716491
TI  - Ischemic preconditioning attenuates capillary no-reflow and leukocyte adherence
      in postischemic pancreatitis.
AB  - BACKGROUND AND AIMS: Ischemic preconditioning (IPC) has been shown to protect
      several organs from ischemia-reperfusion injury. Postischemic microvascular
      dysfunction is considered to be the key mechanism of early graft pancreatitis
      after transplantation. The aim of the study was to determine whether brief
      ischemia and reperfusion before prolonged ischemia followed by reperfusion is
      protective in respect to microcirculatory derangement in postischemic
      pancreatitis. METHODS: In an in-situ model of ischemia-reperfusion was induced in
      the isolated pancreatic tail segment. Wistar rats were randomized to one group (
      n=7/group) with 2-h ischemia and reperfusion (I/R) and another group with 10-min
      ischemia and 10-min reperfusion (IPC) before the prolonged ischemia time.
      Microcirculation was observed for 2 h by intravital-fluorescence microscopy that
      analyzed functional capillary density and leukocyte adherence in postcapillary
      venules. Histological damage was quantified by a semiquantitative score (edema,
      vacuolization, PMN infiltration, necrosis). RESULTS: IPC resulted in a
      significant improvement of functional capillary density (248+/-20 vs 372+/-8 cm(
      1), P<0.001), a significant reduction in leukocyte adherence in postcapillary
      venules (476+/-79 vs 179+/-15 cells/mm(2), P<0.001) and in significantly lower
      histological damage (score 9+/-0.8 vs 5+/-1.4, P<0.001), when compared with the
      ischemia-reperfusion group. CONCLUSION: IPC reduces pancreatic inflammatory
      reaction by preservation of postischemic microcirculation. Therefore, it might
      become a useful procedure before organ procurement in pancreas transplantation.

PMID- 14716493
TI  - Ganglioneuroma mimicking ovarian tumor: a report of a case and review of the
      ganglioneuromas.
AB  - INTRODUCTION: Ganglioneuroma is the most common tumor of the sympathetic nervous
      system in the adults. It occurs most commonly in the mediastinum and
      retroperitoneum and are almost always benign tumors in nature. CASE REPORT: Here,
      we report a case of the retroperitoneal ganglioneuroma mimicking an ovarian tumor
      in a 20 years old female patient.

PMID- 14716492
TI  - Topical exposure of mitomycin C reduces opacification of the residual anterior
      lens capsule and lenticular regeneration after vitrectomy and lensectomy in
      rabbits.
AB  - PURPOSE: To examine the effect of topical administration of mitomycin C (MMC) on
      the opacification of residual anterior lens capsule in a
      vitrectomized/lensectomized eye. METHODS: Adult Japanese albino rabbits ( n=8)
      received two-port vitrectomy and lensectomy with or without topical
      administration of MMC (0.4 mg/ml) to the residual anterior lens capsule in one
      eye under both general and topical anesthesia. Four eyes after vitrectomy and
      lensectomy were exposed to MMC for 1 min and washed out with balanced salt
      solution. After 1 month, the anterior segment of each globe was observed with EAS
      1000 in vivo under general anesthesia and then the enucleated globes were
      observed through the Miyake view. Histological examination was performed.
      RESULTS: During healing intervals in eyes without MMC exposure, regenerated lens
      structure of Soemmering's ring or fibrous tissue was formed in peripheral or
      central areas of the residual capsule, respectively. Both the anterior lens
      capsule opacification and lens fiber regeneration were statistically
      significantly reduced by MMC topical exposure. CONCLUSION: Lens epithelial cells
      produce regenerated lenticular structure and fibrous tissue on the residual
      capsule following vitrectomy and lensectomy in rabbits. Exposure of the residual
      anterior capsule to MMC may be effective in reducing both its opacification and
      lens fiber regeneration after vitrectomy/lensectomy.

PMID- 14716494
TI  - Child-bearing beyond age 50: pregnancy outcome in 59 cases "a concern?".
AB  - OBJECTIVE: To study maternal and perinatal outcomes in healthy women aged 50
      years and older. METHOD: This study was of 59 clinical pregnancies, of which 10
      ended in first trimester spontaneous miscarriage (and were excluded from further
      studies) and 58 live births. This retrospective review of 58 live births in 49
      essentially healthy women (mean [SE] age, [52+/-2.5] years; range 50-55 years),
      with no chronic medical conditions (of which 28 were primigravids). Pregnancy
      outcomes were ascertained by chart review and telephone follow-up. RESULTS: Of
      the 58 live births, 41 were singletons, and 7 were twins, and 1 triplet, for
      which the mean+/-SE gestational age at delivery were 38.1 weeks +/-0.4, 36.2
      weeks +/-0.1 and 34.1 weeks respectively. Birth weights (mean +/- SE) were 3,201
      g+/-10, 2,252 g+/-4 and 1,998+/-95 g respectively. Mean Apgar score +/- SE at 1
      and 5 min were 9.2+/-0.8 and 8.8+/-0.6 respectively. Total cesarean deliveries
      were 73% (36/49). Of singletons 68% (28) were delivered by cesarean section as
      were all multiples. The incidence of pre-eclampsia was 30.6%: mild pre-eclampsia
      20.4% (10/49), severe pre-eclampsia 10.2% (5/49). Gestational diabetes required
      insulin in all 19.5% of women. Anemia was noted in 6.5%. CONCLUSIONS:
      Appropriately screened women, aged 50 years or older, can deliver successfully.
      During pregnancy, they appear to be at increased risk of pre-eclampsia and
      gestational diabetes. A significant majority can expect to deliver via cesarean.

PMID- 14716495
TI  - Prognostic evaluation and review of immunohistochemically detected disseminated
      tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer.
AB  - BACKGROUND: The value of immunohistochemical detection of disseminated tumor
      cells in histopathologically tumor-free lymph nodes (pN0) of patients with
      colorectal cancer is still of uncertain prognostic value. We therefore evaluated
      the immunohistochemical detection rates and their prognostic value comparing
      three different monoclonal antibodies. METHODS: A total of 170 lymph nodes of 85
      patients with curatively resected colorectal carcinoma at UICC stage I or II were
      evaluated for disseminated tumor cells. Frozen sections of each lymph node were
      immunohistochemically stained using three antibodies directed against CEA, CK20,
      and Ber-EP4. The detection rates were compared with histopathological tumor
      parameters and with the patient's survival. The median follow-up time was 86
      months. RESULTS: CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were
      identified microscopically in lymph nodes of 23 patients (27%), 24 patients
      (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated
      tumor cells were found in consecutive sections and stained positive for all three
      monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which
      developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor
      cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients
      (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with
      CEA-positive disseminated tumor cells was 72% compared to 91% of the patients
      without immunohistochemical evidence of tumor cells (p<0.01). While the
      identification of CK20-positive tumor cells was also correlated significantly
      with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed
      to reach significance (p=0.057). Multivariate analysis identified the tumor site
      (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive
      disseminated tumor cells (p<0.03) as independent prognostic factors. CONCLUSION:
      In colorectal carcinoma, the immunohistochemical detection of disseminated tumor
      cells in histopathologically pN0 peritumoral lymph nodes allows the
      identification of a subgroup with a significantly worse prognosis. Nevertheless,
      the prognostic value of immunohistochemically detected disseminated tumor cells
      remains controversial due to the nonuniform data in the literature.

PMID- 14716496
TI  - Angiostatin inhibits experimental liver fibrosis in mice.
AB  - BACKGROUND AND AIMS: Liver fibrosis is a response to chronic hepatic damage,
      which ultimately leads to liver failure and necessitates liver transplantation. A
      characteristic of fibrosis is pathological vessel growth. This type of
      angiogenesis may contribute to the disturbance of hepatocyte perfusion dynamics
      and lead to aggravation of disease. We hypothesized that angiostatin can inhibit
      pathological vessel growth and, consequently, the development of hepatic
      fibrosis. METHODS: Hepatic fibrosis was induced by injection of carbon
      tetrachloride for 5 weeks. Angiostatin mice received carbon tetrachloride for 5
      weeks and angiostatin during weeks 4 and 5. After 5 weeks, immunohistochemistry
      for endothelial cell marker von Willebrand factor and for cell proliferation was
      performed. Angiogenesis was quantified by counting the number of immunopositive
      microvessels. Also, the relative fibrotic surface was determined using Sirius Red
      histostaining and computer image analysis. RESULTS: Immunohistochemistry revealed
      increased expression for von Willebrand factor in fibrotic livers. Immunopositive
      microvessels were localized in fibrotic areas surrounding larger vessels and in
      emerging fibrotic septa. Angiostatin reduced the number of immunopositive
      microvessels by 69% (p<0.001). In addition, angiostatin reduced the relative
      fibrotic area in the liver by 63+/-0.1% (p<0.001). Finally, angiostatin treatment
      was not associated with differences in cell proliferation. CONCLUSIONS:
      Angiostatin inhibits the development of pathological angiogenesis and liver
      fibrosis in mice. These results warrant further evaluation of angiostatin as an
      antifibrotic agent, potentially contributing to the deferment of liver
      transplantation and reduced recurrence of fibrotic disease in the transplanted
      liver.

PMID- 14716497
TI  - Characterization of extracellular lytic enzymes produced by the yeast biocontrol
      agent Candida oleophila.
AB  - The yeast Candida oleophila, the base of the commercial product Aspire, is
      recommended for the control of postharvest decay of citrus and pome fruit.
      Competition for nutrients and space is believed to be the major mode of action.
      Involvement of fungal cell wall-degrading enzymes is also suggested to play a
      role in the mechanism of action of yeast antagonists. The present study showed
      that the yeast C. oleophila is capable of producing and secreting various cell
      wall-degrading enzymes, including exo-beta-1,3-glucanase, chitinase and protease.
      Exo-beta-1,3-glucanase and chitinase were produced and maximized in the early
      stages of growth, whereas protease reached a maximum level only after 6-8 days.
      Production of exo-beta-1,3-glucanase, chitinase and protease was stimulated by
      the presence of cell wall fragments of Penicillium digitatum in the growth
      medium, in addition to glucose. This study also provided evidence that C.
      oleophila is capable of secreting exo-beta-1,3-glucanase into the wounded surface
      of grapefruit. The role of exo-beta-1,3-glucanase ( CoEXG1) in the biocontrol
      activity of C. oleophila was tested using CoEXG1-knockouts and double- CoEXG1
      over-producing transformants. In vitro bioassays showed that wild-type C.
      oleophila and exo-beta-1,3-glucanase over-expressing transformants had similar
      inhibitory effects on spore germination and germ-tube elongation; and both were
      more inhibitory to the fungus than the knockout transformant. In experiments
      conducted on fruit to test the biocontrol activity against infection by P.
      digitatum, no significant difference in inhibition was observed between
      transformants and untransformed C. oleophila cells at the high concentrations of
      cells used, whereas at a lower concentration of yeast cells the knockout
      transformants appeared to be less effective.

PMID- 14716498
TI  - Cloning, functional analysis and expression of a scytalone dehydratase gene (
      SCD1) involved in melanin biosynthesis of the phytopathogenic fungus Bipolaris
      oryzae.
AB  - Scytalone dehydratase is involved in the production of fungal
      dihydroxynaphthalene melanin. We isolated and characterized SCD1, a gene encoding
      scytalone dehydratase, from the phytopathogenic fungus Bipolaris oryzae. Sequence
      analysis showed that SCD1 encodes a putative protein that has 185 amino acids, a
      molecular weight of 21 kDa and 51-75% sequence identity to other fungal scytalone
      dehydratases. Targeted disruption of SCD1 showed that this gene is necessary for
      melanin biosynthesis in B. oryzae. Northern blot analysis showed that SCD1
      transcripts are specifically enhanced by near-ultraviolet (300-400 nm) radiation.

PMID- 14716499
TI  - Preoperative steroid administration: effect on morbidity among patients
      undergoing intestinal bowel resection for Crohns disease.
AB  - Long-term steroid therapy may predispose to increased perioperative morbidity in
      patients undergoing surgery with bowel anastomoses. The aim of our study was to
      review our data to determine if the steroid dosage is associated with the
      incidence of early complications after bowel resection in patients with prolonged
      steroid therapy for Crohns disease (CD). Altogether, 397 patients underwent bowel
      resection with primary intestinal anastomoses for CD between 1982 and 2000 in our
      institution. The mortality and morbidity rates, anastomotic leakage, wound
      infections, intraabdominal abscesses, reoperation rate, and length of
      postoperative hospitalization in patients who were having high-dose (>/= 20 mg of
      prednisolone per day, n = 73) and low-dose (< 20 mg prednisolone per day, n =
      146) steroid therapy for more than 1 month before surgery were compared with
      those of patients ( n = 177) who were not receiving steroids. Statistical
      analysis was performed using Fisher's exact test and Student's t-test, with p <
      0.05 considered significant. The three groups were similar in terms of gender,
      duration since first diagnosis, American Society of Anesthesiologists
      classification, and obesity. Mortality, morbidity, anastomotic leakage, wound
      infections, intraabdominal abscesses, reoperation rate, and average postoperative
      stay were not statistically different in patients with high-dose, low-dose, or no
      steroid therapy. The only factor associated with increased morbidity was a low
      preoperative hemoglobin level. Our results demonstrate that, in patients who are
      undergoing bowel resection for CD, even high-dose prolonged preoperative systemic
      steroid therapy is not associated with increased postoperative complications.

PMID- 14716500
TI  - Higher age predicts adverse outcome and readmission after coronary artery bypass
      grafting.
AB  - The present prospective clinical study was carried out to investigate the effect
      of age on mortality, morbidity, and readmission rates after coronary artery
      bypass grafting (CABG). Data on 1131 consecutive CABG patients were collected in
      a surgical center and in all 18 secondary referral hospitals up to 3 months after
      discharge. Analysis was based on three age groups: 64 years or less (510
      patients), 65 to 74 years (448 patients), and 75 years or more (173 patients).
      Thirty-day mortality rates were 1.6% for the youngest, 5.4% for the middle age
      group, and 6.9% for the oldest. Major complications occurred in 10.8%, 21.2%, and
      24.9% of these patients, respectively. Higher age was associated with more
      readmissions to health care facilities: The oldest patients had a rate twice as
      high as those in the youngest group (34.5% vs. 18.6%). Atrial fibrillation
      (15.4%), chest pain (10.6%), and congestive heart failure (8.5%) were the most
      common reasons for readmission. In conclusion, elderly patients, who are often
      suboptimal candidates for CABG, have higher 30-day mortality, higher morbidity,
      longer length of stay in health care facilities, and an increased risk of
      readmission within 3 months after CABG; age was an independent predictor of 30
      day mortality and postdischarge readmission. Despite the higher risk of adverse
      events after surgery, three out of four elderly patients recover uneventfully.

PMID- 14716502
TI  - Endoscopic retrograde cholangiopancreatography in chronic pancreatitis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) plays an important
      diagnostic and therapeutic role in the management of chronic pancreatitis. New
      techniques are being developed which should further improve outcomes of
      endoscopic intervention. The ultimate role of these therapeutic interventions for
      chronic pancreatitis awaits prospective randomized data demonstrating their
      efficacy and safety in comparison to surgery. Until such time, these often
      difficult techniques should be performed by experienced endoscopists with
      significant experience in pancreatic disease, ideally within the context of
      controlled clinical trials.

PMID- 14716507
TI  - Phylogeography of the component species of broad-leaved evergreen forests in
      Japan, based on chloroplast DNA variation.
AB  - In order to elucidate the past distribution and colonization routes of broad
      leaved evergreen (lucidophyllous) forests, we investigated the intraspecific
      phylogeographic patterns of lucidophyllous forests in Japan and surrounding
      areas. We selected 6 component species with a similar geographic distributions
      growing in Castanopsis-dominant forests. We defined possible important refugia
      during the glacial periods as the regions rich in rare haplotypes (with a
      frequency of 5% or less), or as regions rich in the number of common haplotypes
      (with a frequency of more than 5%). We then located the sites of refuge by
      comparing the intraspecific phylogeographic patterns among 6 component species of
      lucidophyllous forests with respect to these two parameters (i.e., haplotype
      uniqueness and the number of haplotypes). The following results were obtained
      during the course of this study: (1) rare haplotypes were distributed among
      islands around the main islands of Japan; (2) rare subtypes and the greatest
      numbers of common haplotypes were observed in Kyushu, a finding which agreed with
      fossilized pollen data demonstrative of the past existence of refugia in southern
      Kyushu; and (3) rare haplotypes were found on the Muroto Peninsula, and the
      second greatest numbers of common haplotypes were observed on the Kii Peninsula,
      a finding which suggested the existence of additional important refugia along the
      Pacific coast of Japan during the glacial ages.

PMID- 14716508
TI  - Otoacoustic emissions from residual oscillations of the cochlear basilar membrane
      in a human ear model.
AB  - Sounds originating from within the inner ear, known as otoacoustic emissions
      (OAEs), are widely exploited in clinical practice but the mechanisms underlying
      their generation are not entirely clear. Here we present simulation results and
      theoretical considerations based on a hydrodynamic model of the human inner ear.
      Simulations show that, if the cochlear amplifier (CA) gain is a smooth function
      of position within the active cochlea, filtering performed by a middle ear with
      an irregular, i.e., nonsmooth, forward transfer function suffices to produce
      irregular and long-lasting residual oscillations of cochlear basilar membrane
      (BM) at selected frequencies. Feeding back to the middle ear through hydrodynamic
      coupling afforded by the cochlear fluid, these oscillations are detected as
      transient evoked OAEs in the ear canal. If, in addition, the CA gain profile is
      affected by irregularities, residual BM oscillations are even more irregular and
      tend to evolve towards self-sustaining oscillations at the loci of gain
      irregularities. Correspondingly, the spectrum of transient evoked OAEs exhibits
      sharp peaks. If both the CA gain and the middle-ear forward transfer function are
      smooth, residual BM oscillations have regular waveforms and extinguish rapidly.
      In this case no emissions are produced. Finally, and paradoxically albeit
      consistent with observations, simulating localized damage to the CA results in
      self-sustaining BM oscillations at the characteristic frequencies (CFs) of the
      sites adjacent to the damage region, accompanied by generation of spontaneous
      OAEs. Under these conditions, stimulus-frequency OAEs, with typical modulation
      patterns, are also observed for inputs near hearing threshold. This approach can
      be exploited to provide novel diagnostic tools and a better understanding of key
      phenomena relevant for hearing science.

PMID- 14716509
TI  - Structure and growth of the utricular macula in the inner ear of the slider
      turtle Trachemys scripta.
AB  - In general, postembryonic production of inner ear vestibular hair cells (HCs) is
      believed to occur in all nonmammalian vertebrates. However, no study on this
      topic has been published on reptiles and, consequently, it is not known whether
      this also applies to these vertebrates. Therefore, the present study applied
      stereological methods in order to estimate the total number of HCs in turtles of
      varying sizes. The findings are that in prehatchlings the utricular macula (UM)
      contains approximately 4000 HCs as compared to approximately 5000 in juveniles,
      approximately 8000 in medium-sized turtles, and approximately 12,000 in large,
      sexually mature turtles. Scanning electron microscopy (SEM) reveals that
      presumably newly generated HCs with small surface areas and thin stereovilli are
      found in all regions of the UM. Furthermore, it reveals that utricular HCs can be
      classified as belonging to a specific region from the morphology of their apical
      structure. Striolar HCs have a large free oval-to-ovoid surface, a hair bundle
      with numerous stereovilli, and a short kinocilium. Rampary and cotillary HCs have
      smaller and slimmer free surfaces, comparatively fewer stereovilli, but much
      longer kinocilia. In conclusion, the current study demonstrates that
      postembryonic production of HCs does occur in reptiles and thereby supports the
      general view that this is a common trait in all nonmammalian vertebrates.

PMID- 14716510
TI  - Estimates of human cochlear tuning at low levels using forward and simultaneous
      masking.
AB  - Auditory filter shapes were derived from psychophysical measurements in eight
      normal-hearing listeners using a variant of the notched-noise method for brief
      signals in forward and simultaneous masking. Signal frequencies of 1, 2, 4, 6,
      and 8 kHz were tested. The signal level was fixed at 10 dB above absolute
      threshold in the forward-masking conditions and fixed at either 10 or 35 dB above
      absolute threshold in the simultaneous-masking conditions. The results show that
      filter equivalent rectangular bandwidths (ERBs) are substantially narrower in
      forward masking than has been found in previous studies using simultaneous
      masking. Furthermore, in contrast to earlier studies, the sharpness of tuning
      doubles over the range of frequencies tested, giving Q(ERB) values of about 10
      and 20 at signal frequencies of 1 and 8 kHz, respectively. It is argued that the
      new estimates of auditory filter bandwidth provide a more accurate estimate of
      human cochlear tuning at low levels than earlier estimates using simultaneous
      masking at higher levels, and that they are therefore more suitable for
      comparison to cochlear tuning data from other species. The data may also prove
      helpful in defining the parameters for nonlinear models of human cochlear
      processing.

PMID- 14716513
TI  - Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology
      and p53 gene alteration.
AB  - BACKGROUND: Endocrine cell carcinoma of the stomach is characterized by endocrine
      differentiation and aggressive biological behavior, and is frequently accompanied
      by an adenocarcinoma component. Because the carcinogenic parthway and genetic
      alterations remain unclear, we investigated the histogenesis of the tumor by
      histopathological and p53 gene analysis. METHODS: The materials were 68 gastric
      endocrine cell carcinomas and 30 carcinoid tumors, which were resected from 93
      Japanese patients for histopathological and immunohistochemical investigation. We
      also analyzed the concordance of p53 mutational status between the associated
      adenocarcinoma and endocrine cell carcinoma components, using microdissection and
      direct sequencing techniques. RESULTS: An adenocarcinoma component was associated
      with 70.6% (48/68) of endocrine cell carcinomas, of which 42 (87.5%) were of well
      to moderately differentiated type, while 36 of these 42 (85.7%) demonstrated
      histological continuity with the endocrine cell carcinoma components.
      Overexpression of p53 protein was observed in 58.8% (20/34) of cases. Common p53
      mutational status between the two components was revealed in 73.3% (11/15) of
      cases analyzed. In contrast, carcinoid tumors did not exhibit p53 protein
      overexpression (0/15) or gene mutation (0/5). CONCLUSIONS: These data suggest
      that gastric endocrine cell carcinomas predominantly arise from endocrine
      precursor cell clones occurring in preceding adenocarcinoma components
      (particularly the differentiated type), transforming into endocrine cell
      carcinoma during rapid clonal expansion under the influence of p53 gene
      alteration. Endocrine cell carcinoma of the stomach is characterized by endocrine
      differentiation and aggressive biological behavior, and is frequently accompanied
      by an adenocarcinoma component. Because the carcinogenic pathway and genetic
      alterations remain unclear, we investigated the histogenesis of this tumor by
      histopathological and p53 gene analysis.

PMID- 14716514
TI  - Skeletonizing en-bloc gastrectomy for adenocarcinoma in Caucasian patients.
AB  - BACKGROUND: The prognostic relevance of a Japanese-like lymphadenectomy for
      gastric adenocarcinoma is Caucasian patients is not well establishes. METHODS:
      Skeletonizing en-bloc gastrectomy (SEBG) (including removal of the stomach,
      excision of the potentially involved lymph nodes, and skeletonization of the main
      anatomic structures in the upper abdominal floor) was attempted in 216
      consecutive patients with adenocarcinoma of the stomach. Gastrectomy was total in
      143 patients, and subtotal in 72. One debilitated patient had a wedge resection
      of the gastric wall. RESULTS: SEBG was performed in 160 patients (74%), whereas
      56 patients (26%) had a palliative gastrectomy (PG) without lymph node
      dissection. The feasibility rate of SEBG was influenced significantly ( P <
      0.001) by the depth of wall penetration, so that it dropped from 97% in T1 tumors
      to 91%, 65%, and 17% in those classified T2, T3, and T4, respectively. The 5-year
      survival rate, including postoperative mortality (0.9%) was 48% for the whole
      series, 66% after SEBG, and 0% after PG. The 5-year survival rate after SEBG was
      related significantly to the lymph node involvement (N0, 75% vs N+, 54%; P =
      0.008) and to its magnitude (N+, <5 metastatic lymph nodes, 62% versus N+, > or
      =5 metastatic lymph nodes, 39%; P = 0.018). Considering the fact that 9 patients
      died of an unrelated cause before the postoperative term of 5 years, the cancer
      related survival rate 5 years after SEBG was 71% in the whole group of 160
      patients. This survival rate was 82% in patients with normal lymph nodes, versus
      56% in those with metastatic nodes ( P < 0.001). CONCLUSIONS: SEBG was feasible
      in three-quarters of a po-pulation of Caucasian patients operated on for gastric
      adenocarcinoma. SEBG provided a chance for a longterm favorable outcome in three
      quarters of patients with normal lymph nodes and in more than half of those with
      metastatic lymph nodes. These results are similar to those achieved after radical
      gastrectomy in Japanese patients with gastric adenocarcinoma. The prognostic
      relevance of a Japanese-like lymphadenectomy for gastric adenocarcinoma in
      Caucasian patients is not well established.

PMID- 14716515
TI  - Correlation between survivin mRNA expression and lymph node metastasis in gastric
      cancer.
AB  - BACKGROUND: Correlations between the malignant potential and prognosis of cancer
      and abnormal control mechanisms of apoptosis have been discovered in a variety of
      cancers. Survivin is a member of the inhibiting apoptosis protein family that is
      abundant in embryonic and carcinoma tissues. We measured the expression of
      survivin mRNA in gastric cancer to determine whether levels of survivin mRNA
      expression could serve as an index of malignancy. METHODS: Expression of survivin
      mRNA was measured in samples of both gastric cancer and noncancerous tissue from
      107 patients. Survivin mRNA was detected by the real-time polymerase chain
      reaction (PCR) method, and then the relationship between the survivin mRNA level
      and histological diagnosis was analyzed. RESULTS: Expression of survivin mRNA was
      observed in 105 of 107 cancerous tissues and in 101 of 107 noncancerous tissues.
      The Mean value of survivin mRNA expression in cancerous tissue was 5.18 +/- 1.30,
      significantly higher ( P < 0.01) than that in noncancerous tissue, at 4.21 +/-
      1.48. No significant differences were found in the values of survivin mRNA
      expression according to histological classification or according to increasing
      depth of tumor invasion. However, survivin mRNA expression was significantly
      higher ( P < 0.01) in patients displaying lymph node metastasis (5.48 +/- 1.01)
      than in patients without the metastasis (4.70 +/- 1.55). CONCLUSIONS: These
      results indicate that increased survivin mRNA expression begins in the early
      stages of gastric carcinogenesis. Moreover, the level of survivin mRNA expression
      may indicate the potential for lymph node metastasis in patients with gastric
      cancer. Correlations between the malignant potential and prognosis of cancer and
      abnormal control mechanisms of apoptosis have been discovered in a variety of
      cancers. Survivin is a member of the inhibiting apoptosis protein family that is
      abundant in embryonic and carcinoma tissues. We measured the expression of
      survivin mRNA in gastric cancer to determine whether levels of survivin mRNA
      expression could serve as an index of malignancy.

PMID- 14716516
TI  - Laparoscopy significantly improves the perceived preoperative stage of gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to examine the accuracy of laparoscopy is
      staging patients with gastric cancer in comparison with preoperative computed
      tomography (CT) examination. METHODS: One hundred patients out of a consecutive
      series of 258 patients with gastric adenocarcinoma underwent a preoperative
      staging CT followed by a staging laparoscopy. The strengths of the agreement
      between the CT stage, the laparoscopic stage, and the final histopathological
      stage were determined by the weighted Kappa statistic (Kw). RESULTS: The
      strengths of agreement between the CT stage and the final histopathological stage
      were Kw = 0.336 (95% confidence interval [CI]; 0.172-0.5; P = 0.0001) for T stage
      and 0.378 (95% CI; 0.226-0.53; P = 0.0001) for M stage, compared with 0.455 (95%
      CI; 0.301-0.609; P = 0.0001) and 0.73 (95% CI; 0.596-0.864; P = 0.0001) for the
      laparoscopic T and M stages, respectively. Unsuspected metastases that were not
      detected by CT, were found in 21 patients at laparoscopy, all of whom had T3 or
      T4 locally advanced tumors evident on CT. CONCLUSIONS: Preoperative laparoscopic
      staging of gastric cancer is indicated for potential surgical candidates with
      locally advanced disease in the absence of metastases on CT. The aim of this
      study was to examine the accuracy of laparoscopy in staging patients with gastric
      cancer in comparison with preoperative computed tomography (CT) examination.

PMID- 14716517
TI  - Subjects with TNF-A-857TT and -1031TT genotypes showed the highest Helicobacter
      pylori seropositive rate compared with those with other genotypes.
AB  - BACKGROUND: A possible association between Helicobacter pylori seropositivity and
      tumor necrosis factor (TNF) a G-308A has been reported in Korea. The present
      study examined the associations of H. pylori with functional polymorphisms, TNF-A
      G-308A, C-857T, and T-1031C and TNF-B A252G in Japanese subjects. METHODS: The
      total of 1374 study subjects included 241 outpatients who participated in an H.
      pylori eradication program (HPE), 679 first-visit outpatients (FVO) at a regional
      cancer hospital, and 454 local residents who received a health checkup
      examination (HCE). RESULTS: The frequency of the TNF-A -308A allele was only 1.3%
      of 480 chromosomes in the HPE group, so the FVO and HCE groups were not genotyped
      for that polymorphism. The genotype frequency of TNF-A C-857T was 69.2% CC, 27.7%
      CT, and 3.1% TT; that of TNF-A T-1031C was 69.4% TT, 28.1% TC, and 2.5% CC; and
      that of TNF-B A252G was 36.8% AA, 48.2% AG, and 15.0% GG. TNF-A -857T was tightly
      linked to TNF-A -1031T and TNF-B 252A. No significant associations between H.
      pylori seropositivity and polymorphisms of TNF-A C-857T and TNF-B A252G were
      observed. However, a reduced odds ratio adjusted for sex, age, and recruitment
      source was observed for TNF-A -1031CC (0.43; 95% confidence interval, 0.20-0.91)
      relative to TNF-A -1031TT. Subjects with TNF-A -857CC and -1031CC showed the
      lowest seropositivity (38.2% of 34 participants), while those with TNF-A -857TT
      and -1031TT showed the highest (66.7% of 42 participants). CONCLUSIONS: This
      study suggests that the possibly high expression genotype of TNF-A may increase
      susceptibility to persistent H. pylori infection.A possible association between
      Helicobacter pylori seropositivity and tumor necrosis factor ( TNF) A G-308A has
      been reported in Korea. The present study examined the associations of H. pylori
      with functional polymorphisms, TNF-A G-308A, C-857T, and T-1031C, and TNF-B A252G
      in Japanese subjects.

PMID- 14716518
TI  - Subtotal versus total gastrectomy for T3 adenocarcinoma of the antrum.
AB  - BACKGROUND: The role of subtotal or total gastrectomy in the treatment of
      advanced gastric cancer of the antrum with serosal invasion was investigated.
      METHODS: The investigation involved 117 patients with a cancer of the lower third
      of the stomach invading the serosa (pT3) who underwent R0 resection with at least
      D2 lymphadenectomy between 1988 and 1998 at three different Italian centers. The
      choice of surgical procedure (40 total gastrectomies and 77 subtotal
      gastrectomies) was based on the preference of the surgeon; none of the patients
      underwent splenectomy. The Cox regression model was used to evaluate the
      prognostic significance of the type of surgery (subtotal versus total
      gastrectomy), controlling for age, sex, histology, nodal involvement, and
      surgical center. RESULTS: The morbidity and mortality rates did not vary
      significantly according to the type of surgery. Patients undergoing subtotal
      gastrectomy presented a better disease-related survival than patients undergoing
      total gastrectomy ( P = 0.011): the median survival times were, respectively, 38
      months and 23 months, and the overall cumulative 5-year survival rates (95%
      confidence intervals [CI]) were, respectively, 36% (22%-50%) and 22% (11%-37%).
      On univariate analysis, the relative risk (RR) of disease-related death was 1.84
      (1.14-2.97) after total gastrectomy, with respect to subtotal gastrectomy. This
      difference was blunted on multivariate analysis (RR, 1.66; 0.99-2.78): in the
      final model, only nodal metastasis was a significant prognostic factor, while
      type of surgery had a borderline significance ( P = 0.057). CONCLUSIONS: Survival
      after subtotal gastrectomy is not lower than that after total gastrectomy in
      patients with tumor of the antrum invading the serosa. The role of subtotal or
      total gastrectomy in the treatment of advanced gastric cancer of the antrum with
      serosal invasion was investigated.

PMID- 14716519
TI  - Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple
      peritoneal recurrence 8 years after the resection of gastric carcinoma.
AB  - We report a patient with rectal stenosis caused by peritoneal recurrence 8 years
      after a curative resection of advanced stage gastric carcinoma; the recurrence
      was effectively treated with the weekly administration of paclitaxel. The patient
      was a 66-year-old Japanese woman who was admitted to our hospital complaining of
      abdominal pain and frequent bowel movements. She had undergone total gastrectomy,
      due to advanced-stage gastric carcinoma with extensive lymph node metastasis, 8
      years before, and had taken an oral anticancer agent, fluoropyrimidine, for 4
      years after the operation. Colonofiberscopy performed on admission revealed
      circumferential rectal stenosis located 10 cm from the anal verge. Barium enema
      study demonstrated extensive poor expansion of the upper and lower rectum and
      irregularity of the descending colon. Abdominal computed tomography (CT) scanning
      revealed wall thickening in the rectum and descending colon. These findings were
      compatible with rectal stenosis caused by the peritoneal recurrence of gastric
      carcinoma. Weekly administration of paclitaxel was started. The abdominal
      symptoms soon disappeared when the second cycle of paclitaxel was completed, and
      they have not appeared since then. The rectal stenosis was attenuated, as
      confirmed by imaging analyses. Weekly paclitaxel has been effective for more than
      13 months, suggesting that the patient is in a state of tumor dormancy of
      recurrent gastric carcinoma.

PMID- 14716520
TI  - Portal vein thrombosis after splenectomy for gastric malignant lymphoma.
AB  - Portal vein thrombosis (PVT) has rarely been documented in patients after
      splenectomy for gastric malignancy. We report a case of PVT that occurred after
      splenectomy as part of an en-bloc node dissection performed to treat gastric
      malignant lymphoma. A 38-year-old man underwent total gastrectomy and splenectomy
      with en-bloc D2 lymph node dissection. The spleen weighed 480 g. On postoperative
      day (POD) 31, the patient complained of abdominal pain in the right upper
      quadrant accompanied by fever. Moderate elevations of C-reactive protein (CRP),
      aspartate transaminase (AST), and alanine transaminase (ALT) were noted. Contrast
      enhanced computed tomography (CT) and ultrasonography disclosed thrombus in the
      portal vein and the splenic vein. There were no abnormalities in the levels of
      lupus anticoagulant, protein C antigen, protein S antigen, or antithrombin III
      (AT III). A diagnosis of PVT was made, and prompt treatment, including
      intravenous heparin combined with tissue plasminogen activator (tPA) was
      initiated, followed by longterm warfarin. This treatment resulted in clinical
      improvement, but failed to achieve thrombolysis in the portal vein. At follow-up
      after 6 months, the patient complained of postprandial abdominal pain with
      persistent peripheral edema and ascites. This case indicates that splenectomy for
      en-bloc node dissection in gastric malignancy is a possible cause of PVT. Because
      both the symptoms and the laboratory data in PVT are nonspecific, a high level of
      clinical suspicion and a low threshold for obtaining imaging examinations are
      important in the early diagnosis of PVT. Surgeons should remember PVT among
      several other complications whenever patients treated with radical gastrectomies
      are symptomatic and imaging studies are considered necessary.

PMID- 14716521
TI  - Gastric carcinoid tumors with aggressive lymphovascular invasion and lymph node
      metastasis.
AB  - We report a patient with multiple gastric carcinoid tumors without
      hypergastrinemia. An abdominal computed tomography (CT) scan was performed in a
      66-year-old Japanese man who had abdominal discomfort. An abnormal, round, 2.5 cm
      mass close to the lesser curvature of the stomach was detected. Multiple small
      gastric carcinoid tumors were also detected by endoscopy. A total gastrectomy
      with lymph node dissection was performed after it was determined that the round
      mass was a lymph node metastasis of carcinoid tumor. Further pathological
      investigation of the surgical specimen revealed multiple gastric carcinoid tumors
      with severe lymphovascular invasion. The carcinoid tumors in the present patient
      were not related to hypergastrinemia. These lesions could not be grouped as any
      of the three types of gastric carcinoid tumors in the recent classification.
      Furthermore, as a simple distal gastrectomy is the standard treatment for
      multiple carcinoid tumors of the stomach, we recommend that a precise
      histopathological evaluation should be performed before an appropriate curative
      surgical treatment is selected.

PMID- 14716522
TI  - Minute gastric carcinoid tumor with regional lymph node metastasis.
AB  - We report a patient with a minute gastric carcinoid tumor with lymph node
      metastasis, and a small gastric cancer. A 50-year-old man having a diagnosis of
      an elevated lesion on the anterior wall of the gastric body, detected by a series
      of upper gastrointestinal examinations, was referred to the Cancer Institute
      Hospital. Careful upper fluoroscopy disclosed a small superficial depressed
      lesion with converging folds and a superficial elevated lesion covered with
      nonspecific gastric mucosa. With a final preoperative diagnosis of depressed
      early cancer and minute carcinoid tumor of the stomach, made by upper
      gastrointestinal examinations including biopsy, the patient underwent segmental
      gastrectomy and perigastric lymph node dissection. Histological examination of
      the resected specimen revealed a lymph node metastasis from a gastric carcinoid
      tumor of 5-mm diameter, in addition to an early gastric cancer of poorly
      differentiated adenocarcinoma. Small gastric carcinoid tumors have been regarded
      as being benign neoplasms biologically. However, the case we present suggests
      that attention should be paid to the possibility of metastasis at the time of
      treatment for a minute sporadic gastric carcinoid tumor. We therefore discuss the
      malignant potential of these tumors, mainly from the viewpoint of
      histopathological classification, to gain understanding so that the patients can
      be treated adequately.

PMID- 14716523
TI  - Gastric cancer diagnosed in a patient with crescentic glomerulonephritis.
AB  - Malignant neoplasms are rarely associated with glomerular changes. The glomerular
      lesion seen most often in patients with malignancies is membranous
      glomerulonephritis. We report here a case of gastric cancer associated with
      rapidly progressive glomerulonephritis (RPGN). A 57-year-old man was admitted to
      our hospital with acute renal failure. Renal biopsy was performed, and the
      diagnosis was RPGN. Steroid treatment was instituted, but was complicated by
      hematemesis, and an early-stage gastric cancer was found after endoscopic
      examinations. Gastric biopsy revealed gastric adenocarcinoma. The patient's renal
      function improved with corticosteroid treatment and hemodialysis, and total
      gastrectomy was performed. The improvement in renal function persisted after the
      removal of the gastric cancer, and the RPGN and cancer have been in remission for
      3 years.

PMID- 14716524
TI  - Colliding gastric and intestinal phenotype well-differentiated adenocarcinoma of
      the stomach developing in an area of MALT-type lymphoma.
AB  - A 73-year-old man presented with an abnormal gastric shadow during a check-up of
      atomic bomb survivors. Radiological examination and endoscopy of the upper
      gastrointestinal tract revealed a protruding tumor, type 0-I+IIa, on the lesser
      curvature of the midstomach. An initial diagnosis of early gastric cancer was
      made and a segmental gastrectomy was planned. However, distal gastrectomy with D3
      lymph node dissection was necessary, because intraoperative frozen section showed
      that the paraaortic lymph nodes (N3) were positive for cancer. The tumor in the
      resected specimen was, microscopically, a well-differentiated tubular
      adenocarcinoma (tub1) with pT2 (MP), pN3, ly2, and v1, in final (f) stage IV. The
      tumor cells of the type 0-I segment appeared as gastric phenotype and those of
      the type 0-IIa segment as intestinal phenotype. The border between the two was
      distinct. The tumor had focally invaded the muscularis propria where only the
      gastric phenotype was shown and the histological type became less differentiated.
      Thus, special attention should be paid to possible unexpected deep-wall invasion
      and lymph node metastasis in well-differentiated adenocarcinomas of the gastric
      phenotype. Further, in this patient, diffusely proliferating low-grade lymphoma
      was also observed incidentally in the gastric mucosa within and around the
      carcinoma. This was diagnosed as mucosa-associated lymphoid tissue (MALT)-type
      lymphoma with aberrant expression of BCL10. Finally, this case was considered to
      be a colliding gastric and intestinal phenotype well-differentiated
      adenocarcinoma of the stomach developed in an area involved by MALT-type
      lymphoma. Because no Helicobacter pylori was detected throughout the mucosae and
      the patient had no history of its infection, the three tumors may have developed
      under the same conditions as those seen in Helicobacter pylori infection, but
      without this infection.

PMID- 14716525
TI  - Clinical and neurological abnormalities in adult celiac disease.
AB  - We assessed the occurrence of neurological signs and symptoms in adult patients
      with celiac disease and evaluated the correlation between neurological features
      and diet. A total of 176 patients and 52 age-matched controls underwent a
      semistructural interview and a neurologic examination. The effect of gluten-free
      diet was evaluated by comparing the prevalence of signs and symptoms among
      patients adhering to a gluten-free diet and patients on an unrestricted diet. The
      occurrence of headache, dysthymia and signs of peripheral neuropathy was
      significantly higher in patients with celiac disease than in control subjects.
      Adherence to a strict gluten-free diet was associated with a significant
      reduction of headache, dysthymia, cramps and weakness, but did not modify the
      occurrence of paresthesia or hyporeflexia. Neurological signs and symptoms are
      associated with celiac disease and can be ameliorated by a gluten-free diet.

PMID- 14716526
TI  - Prophylactic treatment of episodic cluster headache with intravenous bolus of
      methylprednisolone.
AB  - We evaluated the efficacy of intravenous boluses of methylprednisolone followed
      by prednisone as a prophylactic treatment for episodic cluster headache. Fourteen
      male patients (mean age, 42.54 years) with episodic cluster headache were treated
      with 250-mg boluses of methylprednisolone on 3 consecutive days, followed by
      prednisone (90 mg/day orally) with gradual tapering in four weeks. Headache
      parameters of the active phases treated with methylprednisolone were compared
      with those of previous active phases in the same patients treated with other
      prophylactic medications. The primary efficacy criterion was decrease in the
      frequency of attacks during the first month of treatment. The statistical
      differences were calculated using Wilcoxon's test. The attacks were significantly
      less frequent in the active phases treated with methylprednisolone boluses than
      those treated with other medications ( p<0.05). This treatment seems to be more
      effective than the usual prophylactic treatments for episodic cluster headache.

PMID- 14716527
TI  - Epileptic seizures in multiple sclerosis: clinical and EEG correlations.
AB  - Epileptic seizures occur more frequently in multiple sclerosis (MS) patients than
      in the general population. We evaluated clinical, electroencephalographic (EEG)
      and magnetic resonance imaging (MRI) findings, as well as EEG-MRI correlations
      and the response to antiepileptic drugs (AEDs) in 270 consecutive patients with
      definite MS referred to our Department from 1995 to 2002. Thirteen (4.8%)
      subjects experienced epileptic seizures. In four cases, seizures manifested
      within 1-2 years ("early-onset"), and in six cases within 8-23 years ("late
      onset") of MS diagnosis. Seizures were usually partial with secondary
      generalization. Thus, acute symptomatic seizures occurred in three cases.
      Epilepsy usually appeared late in the course of disease, although a single
      episode or a cluster of seizures can represent the onset symptom or a relapse of
      MS. Prognosis of epilepsy during the course of MS is usually good but the choice
      of AEDs remains a matter of debate.

PMID- 14716528
TI  - Psychological and social aspects in management of Alzheimer's patients: an
      inquiry among caregivers.
AB  - A survey in the cities of Genoa and Savona (Italy) was performed to examine
      stress levels in caregivers of patients with Alzheimer's disease in the context
      of a project of the Italian Ministry of Health named Cronos. It offered free
      anticholinesterase inhibitor therapy to patients who addressed dedicated
      Neurological Units; in this occasion caregivers could be invited to express the
      main difficulties encountered in managing demented people during an interview
      conducted by health personnel of the Neurophysiology Service. Caregivers were
      mainly women, daughters or spouses, with a medium educational level, retired,
      housekeepers, employees or teachers; they claimed a lowering of economic standard
      of living of the family owing to extra expenses for assistance. Satisfaction was
      expressed towards specialists, while support by general practitioners and other
      sanitary services was usually lacking and money contribution from the government
      or territorial services was considered inadequate. From the emotional point of
      view, caregivers claim loss of free time, friendships and hobbies, and feel
      isolated in the social context; sometimes the patient's death is thought of as a
      solution. A strong need for information and support is clearly emerging and any
      further interventions should take these requirements into consideration.

PMID- 14716529
TI  - A normative study of a shorter version of Raven's progressive matrices 1938.
AB  - A shorter four-set (A, B, C, D) version of Raven's progressive matrices 1938
      (PM38) has gained increasing use in neuropsychological assessment. No normative
      data spanning across a wide age range are, however, available. This study
      collected norms for the shorter version of PM38, established an inferential cut
      off value and derived equivalent scores in a sample of 248 individuals from 20 to
      89 years of age, evenly distributed across sex, age and education levels. Results
      showed significant effects of age and education but no effect of sex on
      performance. These normative data will complement existing norms for other tests,
      will increase the wealth of neuropsychological tools for which normative data are
      available for the Italian population, and may be useful in the early detection of
      individuals at risk of developing dementia.

PMID- 14716530
TI  - Interferon beta treatment of MS in the daily clinical setting: a 3-year post
      marketing study.
AB  - We performed a post-marketing study of patients with multiple sclerosis (MS)
      attending the outpatient service to evaluate the impact of interferon beta-1b
      (IFNbeta-1b) in the daily clinical setting. The absolute changes in relapse
      frequency and in the mean EDSS score over a three-year period were compared
      between 83 patients with relapsing remitting MS treated with IFNbeta-1b and 83
      RRMS patients who did not take the drug. Annualized relapse frequency
      significantly decreased in patients undergoing therapy while no statistically
      significant changes in EDSS score were observed. These findings point out the
      role of post-marketing studies in evaluating the impact of approved drugs in the
      daily clinical setting in terms of safety and tolerability. Furthermore, our
      results confirm the positive effect of immunomodulatory treatment in decreasing
      the occurrence of inflammatory events.

PMID- 14716531
TI  - Study of visual evoked potentials in the assessment of the central optic pathways
      in leprosy patients.
AB  - We evaluated the possible involvement of central optic pathways (COP) in leprosy
      patients with visual evoked potentials, an easy, sensitive and reliable
      noninvasive method for evaluation of COP. In 37 patients with lepromatous leprosy
      and in 37 age-matched controls, we measured reversal pattern visual evoked
      potentials (RP-VEP) and nerve conduction parameters. The mean latency value of
      positive peak P100 in leprosy patients was significantly delayed compared to that
      of controls (patients, 108.02+/-9.61 ms in left eye and 108.23+/-8.51 ms in right
      eye; controls, 96.22+/-4.20 ms in left eye and 95.75+/-4.03 ms in right eye;
      p<0.05). Abnormally delayed P100 latency was recorded in 5 of 37 leprosy patients
      (13.5%). The mean amplitude of P100 latency in leprosy patients was smaller than
      that of controls (patients, 8.7+/-5.6 micro V in left eye and 9.5+/-4.8 micro V
      in right eye; controls, 10.7+/-4.6 micro V in left eye and 10.5+/-5.1 micro V in
      right eye), but this difference was not significant. No correlation was observed
      between abnormalities of RP-VEP and sensorimotor nerve conduction parameters.
      This study suggests that involvement of COP may develop in patients with
      lepromatous leprosy. RP-VEP measurement, which can be easily and rapidly
      performed in an EMG laboratory using standard equipment, can show these
      alterations.

PMID- 14716532
TI  - Carotid endarterectomy and gliofibrillar S100b protein release.
AB  - Increased levels of the gliofibrillar S100b protein can be detected during
      carotid endarterectomy (CEA). Whether the S100b protein increase is marker of
      brain ischemic sufferance and predictor of cognitive decline is controversial.
      Twenty-eight patients underwent clinical assessment and cranial computed
      tomography (CT) 24-48 hours before and 3 months after CEA. S100b serum levels
      were evaluated before surgery, at cross-clamping, 10 minutes later, at
      declamping, and 24-48 hours and 10-12 weeks after CEA. Increased S100b levels
      were detected in 11 patients (39%); eight (73%) of these patients had symptomatic
      carotid artery disease. Increased S100b level correlated with history of TIA or
      stroke ( p=0.005), low mini-mental state examination score ( p=0.02), and
      ischemic infarctions at preoperative CT ( p=0.03). Slight and transient increased
      S100b levels were detected in 39% of patients during CEA. The protein levels
      increased despite the absence of clinical events during surgery. Our findings
      suggest a failure of compensatory hemodynamic or metabolic mechanisms in peri
      ischemic tissue, whose longterm effects on cognition remain to be investigated.

PMID- 14716533
TI  - Isolated medial medullary infarction due to vertebral artery dissection.
AB  - A 54-year-old man developed left hemiparesis and tactile and deep sensory
      disturbance following onset of rightside cervical pain. These symptoms resulted
      from an isolated infarct in the right medial area of the upper medulla oblongata
      and intracranial vertebral artery (VA) dissection. Atherosclerotic disease of the
      VA is the most common cause of medial medullary infarction. In past reports of
      isolated medial medullary infarction, only a few cases involved VA dissection.

PMID- 14716534
TI  - Long-term interferon-beta treatment for multiple sclerosis.
AB  - The aim of our study was to analyze the dropout rate in patients with relapsing
      remitting multiple sclerosis (RRMS) under long-term treatment with the three
      commercially available interferon beta (IFNbeta) preparations. According to the
      drug taken, we divided 122 RRMS patients into 4 groups: Betaferon group, 56
      patients taking INFbeta-1b (24 MIU weekly, subcutaneous injections); Avonex
      group, 38 patients taking IFNbeta-1a (6 MIU weekly, intramuscularly); Rebif
      group, 18 patients taking INFbeta-1b (18 MIU subcutaneously). Ten patients who
      shifted from Betaferon to Avonex were included in a fourth group. Dropouts were
      registered every trimester with the related cause. Data were evaluated using
      Kaplan-Meier survival analysis and log-rank test. During the observation period
      of five years, 48 patients (39.9%) dropped out: 48% of the patients in Betaferon
      group withdrew at a median of 758 days, 26% of the Avonex group at 356 days; 38%
      of the Rebif group at 421 days, and 40% of those who shifted from Betaferon to
      Avonex at 259 days. The differences between groups were not significant on
      survival analysis. Patients receiving higher dose treatment (Betaferon and Rebif
      groups) dropped out mainly for clinical adverse events; conversely, patients
      receiving lower dose therapy (Avonex group) dropped out most often for
      inefficacy. Patients who shifted to a lower dose treatment (fourth group) had a
      dropout rate similar to that of the initial treatment. Our data showed that one
      third of the patients stopped the therapy, mostly for adverse events and then for
      inefficacy, while the remaining two-thirds were still on treatment without
      problems up to 5 years of follow-up. Compliance seems related to the dose of the
      drug, but further analysis is needed to confirm our data.

PMID- 14716537
TI  - Organic acids and water-soluble phenolics produced by Paxillus sp. 60/92 together
      show antifungal activity against Pythium vexans under acidic culture conditions.
AB  - Ectomycorrhizal fungi can produce antifungal compounds in vitro as well as in
      symbiosis with the host plant that can reduce root diseases. The objective of
      this study was to isolate antifungal compounds from culture filtrate of Paxillus
      sp. 60/92, which can form mycorrhizas with Picea glehnii seedlings. Culture
      filtrate of Paxillus sp. 60/92 showed antifungal activity against Pythium vexans
      at pH 3-4 but not at pH 5-10, although sterile MMN-b liquid medium (pH 3-10) did
      not show antifungal activity. Upon separation of antifungal compounds in the
      culture filtrate, antifungal activity was detected in the organic acid and water
      soluble phenolics fractions adjusted to pH 3. Although antifungal activity of
      individual fractions was lower than that of the culture filtrate, a mixture of
      these fractions showed antifungal activity similar to that of the culture
      filtrate. Furthermore, antifungal activity of oxalic acid, which is known to be
      produced by Paxillus involutus, was increased by mixing with the water-soluble
      phenolic fraction. Our findings indicate that Paxillus sp. 60/92 produces organic
      acids and water-soluble phenolics that together show antifungal activity at pH 3
      4 against P. vexans.

PMID- 14716538
TI  - Robot-assisted laparoscopic cholecystectomy versus conventional laparoscopic
      cholecystectomy: a comparative study.
AB  - BACKGROUND: The efficacy of conventional laparoscopic cholecystectomy (CLC) was
      compared with robot-assisted laparoscopic cholecystectomy (RLC). Surgical
      trainees performed the LC to avoid the surgeon's experience bias. METHODS: Two
      surgical trainees performed 10 CLCs and 10 RLCs at random with a Zeus-Aesop
      Surgical Robotic System. The primary efficacy parameters were the total time and
      the number of actions involved in the procedure. The secondary parameters were
      setup and dissection times, and the number of grasping and dissection actions.
      Surgical complications were evaluated. RESULTS: For CLC and RLC, respectively,
      the total times were 95.4 +/- 28 min and 123.5 +/- 33.3 min and the total actions
      were 420 +/- 176.3 and 363.5 +/- 158.2. For CLC, the times required for setup (21
      +/- 10.4 min) and dissection (50.2 +/- 17.7 min) were less than for RLC (33.8 +/-
      11.3 min and 72 +/- 24.3 min, respectively). The numbers of grasping and
      dissection actions were not significantly different: 41.4 +/- 26.5 and 378 +/-
      173.7, respectively, for CLC versus 48.9 +/- 27 and 314.6 +/- 141.9,
      respectively, for RLC. CONCLUSION: Although feasible, RLC requires significantly
      more time than CLC because of slower performed actions.

PMID- 14716540
TI  - Correlation of radiographic and manometric findings in patients with ineffective
      esophageal motility.
AB  - BACKGROUND: Ineffective esophageal motility disorder (IEM) is a new,
      manometrically defined, esophageal motility disorder, associated with severe
      gastroesophageal reflux disease (GERD), GERD-associated respiratory symptoms,
      delayed acid clearance, and mucosal injury. Videoesophagram is an important,
      inexpensive, and widely available tool in the diagnostic evaluation of patients
      with esophageal pathologies. The efficacy of videoesophagography has not been
      rigorously examined in patients with IEM. The aim of this study was to determine
      the diagnostic value of videoesophagography in patients with IEM. METHODS: The
      radiographic and manometric findings of 202 consecutive patients presenting with
      foregut symptoms were evaluated. IEM was defined by strict manometric criteria.
      All other named motility disorders such as achalasia were excluded.
      Videoesophagography was performed according to a standard protocol. RESULTS: Of
      patients in this cohort, 16% (33/202) had IEM by manometric criteria. Of IEM
      patients, 55% (18/33) had an abnormal videoesophagram, while in 45% (15/33) this
      test was read as normal. Only 11% (15/137) of patients with a normal
      videoesophagram were found to have IEM. Sensitivity of videoesophagram was 54.6%,
      specificity 72.2%, positive predictive value only 27.7%, and negative predictive
      value 89.1% in the diagnosis of IEM. CONCLUSIONS: These data show that
      videoesophagram is relatively insensitive in detecting patients with IEM and
      should not be considered a valid diagnostic test for this disorder. We conclude
      that esophageal manometry is an indispensable diagnostic modality in the workup
      of a patient with suspected of IEM.

PMID- 14716543
TI  - Incidence of incisional recurrence after thoracoscopy.
AB  - BACKGROUND: Incisional recurrence after thoracoscopic surgery has been reported
      infrequently. In recent years, several reports of port-site recurrence after
      laparoscopic oncologic procedures have been published. This study evaluates the
      incidence of incisional recurrence among patients with intrathoracic malignancy
      after diagnostic and therapeutic thoracoscopy. METHODS: The medical records of
      all patients with intrathoracic malignancies who underwent thoracoscopic
      procedures between 1992 and 1998 at Chang Gung Memorial Hospital Linkou Medical
      Center were reviewed. Information includes preoperative tumor status,
      thoracoscopic findings, primary tumor location, tumor pathology, procedures
      performed, and perioperative complications were recorded. RESULTS: A total of
      1,069 patients with known intrathoracic malignancies underwent thoracoscopy. The
      mean follow-up time was 17.1 months (range, 1-68 months). Two recurrences at the
      incision were identified (0.19%). Both patients with incision-site recurrence had
      advanced intrathoracic disease at the time of thoracoscopy. The one patient had a
      malignant pleural effusion (T4), and the other had diffuse pleural metastasis.
      CONCLUSION: The incidence of incisional recurrence after thoracoscopic oncologic
      surgery is very low. When recurrence occurs at the incision, it is associated
      most commonly with advanced intrathoracic disease. Additional patients and a
      longer follow-up evaluation are required, however, to confirm this observation.

PMID- 14716541
TI  - Optimization of cardiac preload during laparoscopic donor nephrectomy: a
      preliminary study of central venous pressure versus esophageal Doppler
      monitoring.
AB  - BACKGROUND: While the popularity of laparoscopic donor nephrectomy (LDN) has
      increased, concern persists about the potential deleterious effects of
      pneumoperitoneum on renal function. Thus, preload optimization with vigorous
      intravenous hydration has been recommended. The purpose of this study was to
      compare central venous pressure (CVP) monitoring with a noninvasive measure of
      cardiac preload (esophageal Doppler) during LDN. METHODS: Thirteen patients were
      studied. Following induction of general anesthesia, a Doppler probe was inserted
      in the lower third of the esophagus to measure flow time corrected for heart rate
      (FTc), which is an index of preload. In 10 patients, a catheter was placed in the
      right internal jugular vein and CVP measured. CVP and FTc were measured at
      baseline in the supine and right lateral decubitus positions, then 15 and 60 min
      after the establishment of CO(2) pneumoperitoneum (12-15 mmHg). IV fluids were
      increased if the FTc fell below 300 msec. Results are expressed as means (+/-SD).
      Data were analyzed using repeated measures ANOVA. RESULTS: Lateral positioning
      and pneumoperitoneum significantly increased CVP from baseline ( p < 0.01), while
      the FTc did not change ( p = 0.57). After 60 min of pneumoperitoneum, the FTc was
      <300 msec in only one patient. CONCLUSION: CVP is not an accurate guide for
      administration of IV fluids during LDN. Esophageal Doppler monitoring can be used
      to noninvasively follow changes in preload during LDN and is worthy of further
      study.

PMID- 14716545
TI  - Burst strength of laparoscopic and open hernia repair.
AB  - BACKGROUND: There are few reports of overall strength of laparoscopic and open
      incisional hernia repair. METHODS: After anesthesia, a 2-inch circular defect was
      made in the abdominal wall of 28 female swine. Gore-Tex DualMesh Biomaterial (W.
      L. Gore & Associates, Flagstaff, AZ) was used for all repairs. Sixteen animals
      underwent open repair and 12 underwent laparoscopic repair. Burst strength was
      detected within 2 weeks and at 6 weeks by euthanizing the animals and
      insufflating the abdominal cavity with water while measuring the intraabdominal
      pressure until it could no longer be pressurized. RESULTS: Three events occurred
      after insufflation: rupture around patch (R), dissection from insufflation or
      pressure monitoring sites (D), or rectal prolapse (P). Failure after open early
      repair occurred at 289 (range 219-388) mmHg with 7-R, 1-P and late 289 (196-343)
      mmHg with 1-R, 6-P. Failure after laparoscopic early repair occurred at 259 (191
      388) mmHg with 4-R, 1-P, 1-D and late 291 (140-330) mmHg with 2-R, 1-P, 3-D. Late
      groups were less likely to rupture. CONCLUSION: Both hernia repairs are durable
      at early and late periods. Tissue ingrowth adds to repair strength. We could not
      show that one repair was stronger than the other. Nonetheless, laparoscopic
      repair tended to degrade by dissection, which was our highest pressure event.

PMID- 14716552
TI  - Long-term symptoms following endoscopic sphincterotomy for common bile duct
      stones.
AB  - BACKGROUND: Endoscopic sphincterotomy (ES) has an important role in the
      management of biliary stones. However, the long-term effects of free
      duodenobiliary reflux are not established, and it may lead to low-grade
      morbidity. METHODS: We used a questionnaire survey to assess the prevalence of
      symptoms of biliary disorder in patients who had undergone endoscopic retrograde
      cholangio pancreatography (ERCP) and ES under the care of a single surgeon
      (R.J.R.G) between November 1993 and May 1998. RESULTS: ES was carried out on 136
      patients during this period. Current addresses were available for 94 patients,
      and 54 of them (57%) responded. Patients were surveyed a mean of 43 months after
      ES. Only 42.1% of patients denied having any symptoms. Nausea and pale stools
      were reported by 28% and 26% of patients, respectively, and nearly one-fifth of
      patients had symptoms suggestive of cholangitis. In addition, 18.5% of patients
      experienced one or more symptoms frequently. CONCLUSION: Severe long-term
      symptoms are uncommon following ES; however, a significant minority of patients
      do suffer occasional symptoms that suggest biliary dysfunction.

PMID- 14716555
TI  - Marine reserves: long-term protection is required for full recovery of predatory
      fish populations.
AB  - No-take marine reserves are advocated widely as a potential solution to the loss
      of marine biodiversity and ecosystem structure, and to over-fishing. We assess
      the duration of protection required for unfished populations of large predatory
      reef fish to attain natural states. We have monitored two marine reserves at
      Sumilon and Apo Islands, Philippines, regularly for 17 years (1983-2000). The
      biomass of large predatory fish was still increasing exponentially after 9 and 18
      years of protection at Sumilon and Apo reserves, respectively. There was little
      evidence that the rate of accumulation of biomass inside the reserves was slowing
      down even after so many years of protection. This suggests that the length of
      time to full recovery will be considerable. We made two assumptions in order to
      estimate this period. Firstly, that biomass growth will follow the logistic
      model. Secondly, the conservative assumption that biomass had already attained
      90% of the local carrying capacity of the environments in the reserves. We
      conclude that the time required for full recovery will be 15 and 40 years at
      Sumilon and Apo reserves, respectively. Such durations of recovery appear
      consistent with known life history characteristics of these fish, and with
      empirical data on recovery rates of heavily exploited fish stocks. By the time
      the full fisheries or ecosystem benefits from such reserves are apparent, human
      populations and impacts will have doubled in much of the developing world. Thus,
      networks of such reserves need to be implemented immediately. Furthermore, the
      management mechanisms for the reserves need to be successful over timescales of
      human generations.

PMID- 14716554
TI  - Effects of stoichiometric dietary mixing on Daphnia growth and reproduction.
AB  - Herbivores often encounter nutritional deficiencies in their diets because of low
      nutrient content of plant biomass. Consumption of various diet items with
      different nutrient contents can potentially alleviate these nutritional
      deficiencies. However, most laboratory studies and modeling of herbivorous
      animals have been done with diets in which all food has uniform nutrient content.
      It is not clear whether heterogeneous versus uniform food of equal overall
      nutrient content is of equivalent nutritional value. We tested the effects of
      dietary mixing on performance of a model organism, Daphnia. We fed two species of
      Daphnia ( D. galeata, D. pulicaria) with diets of equivalent bulk stoichiometric
      food quality (C:P) and studied whether they would produce equivalent performance
      when C:P was uniform among cells or when the diet involved a mixture of high C:P
      and low C:P cells. Daphnia were fed saturating and limiting concentrations of a
      uniform food of moderate C:P (UNI) or mixtures (MIX) of high C:P (LOP) and low
      C:P (HIP) algae prepared to match C:P in UNI. Daphnia were also fed HIP and LOP
      algae separately. Juvenile growth rate and adult fecundity were measured. D.
      galeata performance in UNI and MIX treatments did not differ, indicating that
      partitioning of C and P among particles did not affect dietary quality.
      Similarly, D. pulicaria's performance was similar in the MIX and UNI treatments
      but only at low food abundance. In the high food treatment, both growth and
      reproduction were higher in the MIX treatment, indicating some benefit of a more
      heterogeneous diet. The mechanisms for this improvement are unclear. Also, food
      quality affected growth and reproduction even at low food levels for both D.
      pulicaria and D. galeata. Our results indicate that some species of zooplankton
      can benefit from stoichiometric heterogeneity on diet.

PMID- 14716556
TI  - Cold temperature increases winter fruit removal rate of a bird-dispersed shrub.
AB  - We tested the hypothesis that winter removal rates of fruits of wax myrtle,
      Myrica cerifera, are higher in colder winters. Over a 9-year period, we monitored
      M. cerifera fruit crops in 13 0.1-ha study plots in South Carolina, U.S.A. Peak
      ripeness occurred in November, whereas peak removal occurred in the coldest
      months, December and January. Mean time to fruit removal within study plots was
      positively correlated with mean winter temperatures, thereby supporting our
      hypothesis. This result, combined with the generally low availability of winter
      arthropods, suggests that fruit abundance may play a role in determining winter
      survivorship and distribution of permanent resident and short-distance migrant
      birds. From the plant's perspective, it demonstrates inter-annual variation in
      the temporal component of seed dispersal, with possible consequences for post
      dispersal seed and seedling ecology.

PMID- 14716557
TI  - Recurrent ureteric fibroepithelial polyp in a child.

PMID- 14716558
TI  - Refractory bleeding following major surgery of a giant sacrococcygeal teratoma in
      a premature infant: successful use of recombinant factor VIIa.

PMID- 14716559
TI  - Ethical principles and operational guidelines for good clinical practice in
      paediatric research. Recommendations of the Ethics Working Group of the
      Confederation of European Specialists in Paediatrics (CESP).
AB  - A child has the full right of protection of his/her life by provision of optional
      medical care. There is a need in paediatrics for better evidence based practice
      founded on quality research into efficacy and safety of children's medications.
      To protect the best interests of the child one must balance the ethical demand to
      do clinical studies with the necessity to avoid doing harm. To achieve this end
      good clinical practice in paediatric research demands that studies comply with
      the Declaration of Helsinki, ICH topic E11, EU Directives and other relevant
      international guidelines. Evident differences in physiology, pharmacology,
      pharmacokinetics and pharmacodynamics between children of differing ages and
      between children and adults demand properly constructed and conducted studies
      that respect the special somatic, emotional and mental needs of children. To
      justify any research project one must balance the benefit/risk ratio, provide
      experienced, competent personnel and infracture, obtain adequate informed
      consent/assent, and have the study evaluated and approved by an ethics committee
      containing expertise on the rights and needs of children.

PMID- 14716560
TI  - Partial anomalous pulmonary vein connection: an underestimated cardiovascular
      defect in Ullrich-Turner syndrome.
AB  - Congenital cardiovascular defects, commonly affecting the aortic valve or the
      aortic arch (50% to 70%), are seen in ca. 17%-44% of patients with Ullrich-Turner
      syndrome (UTS). However, there are only 36 case reports worldwide on the
      coincidental finding of partial anomalous pulmonary vein connection (PAPVC) in
      UTS. In 4 out of 108 patients with UTS seen in our clinic, PAPVC was suspected
      echocardiographically and confirmed by angiography in three patients. Surgical
      correction was performed in one patient with right ventricular enlargement. PAPVC
      can lead to right ventricular volume load and hypertrophy in adolescence. Early
      diagnosis and when necessary treatment is recommended. CONCLUSION: cardiological
      evaluation in patients with Ullrich-Turner syndrome should pay special attention
      to partial anomalous pulmonary vein connection.

PMID- 14716561
TI  - Nitric oxide plays a central role in determining lateral root development in
      tomato.
AB  - Nitric oxide (NO) is a bioactive molecule that functions in numerous
      physiological processes in plants, most of them involving cross-talk with
      traditional phytohormones. Auxin is the main hormone that regulates root system
      architecture. In this communication we report that NO promotes lateral root (LR)
      development, an auxin-dependent process. Application of the NO donor sodium
      nitroprusside (SNP) to tomato ( Lycopersicon esculentum Mill.) seedlings induced
      LR emergence and elongation in a dose-dependent manner, while primary root (PR)
      growth was diminished. The effect is specific for NO since the NO scavenger 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) blocked the
      action of SNP. Depletion of endogenous NO with CPTIO resulted in the complete
      abolition of LR emergence and a 40% increase in PR length, confirming a
      physiological role for NO in the regulation of root system growth and
      development. Detection of endogenous NO by the specific probe 4,5
      diaminofluorescein diacetate (DAF-2 DA) revealed that the NO signal was
      specifically located in LR primordia during all stages of their development. In
      another set of experiments, SNP was able to promote LR development in auxin
      depleted seedlings treated with the auxin transport inhibitor N-1
      naphthylphthalamic acid (NPA). Moreover, it was found that LR formation induced
      by the synthetic auxin 1-naphthylacetic acid (NAA) was prevented by CPTIO in a
      dose-dependent manner. All together, these results suggest a novel role for NO in
      the regulation of LR development, probably operating in the auxin signaling
      transduction pathway.

PMID- 14716562
TI  - Induction of phlorotannins in the brown macroalga Ecklonia radiata (Laminariales,
      Phaeophyta) in response to simulated herbivory--the first microscopic study.
AB  - We investigated, for the first time in a microscopic study, the accumulation of
      phlorotannins as a possible inducible chemical defence against herbivory.
      Ecklonia radiata (C. Agardh) was mechanically wounded with a cork borer,
      simulating grazer action, and at intervals of 0, 1, 2, 3, 5, 7 and 9 days after
      wounding the distribution of phlorotannins and other structural changes were
      examined by light, fluorescence and electron microscopy. In brown algal cells,
      phlorotannins (polyphenolic compounds) occur in vesicles known as physodes. In E.
      radiata, most of the physodes were found in the outer epidermal cell layer, but
      some were present in the cortical cells and in the innermost medullary cells
      (sieve elements and hyphal cells). The wound-healing process could be divided
      into three stages: (i) 'closing' of the medulla by the formation of new medullary
      cells, (ii) accumulation of phlorotannins (physodes) at the wound area (first in
      the medullary cells and then in the cortical cells) and in the medullary tissue
      further away from the wound, and (iii) formation of a new epidermis. The
      accumulation of phlorotannins started on day 1 and was evident from day 3 on. Our
      results show structural wound-healing and support wound-sealing functions for
      phlorotannins and the view that phlorotannins might be considered as inducible
      anti-herbivory agent in E. radiata. Our results strongly demonstrate the
      importance of detailed microscopic studies, in addition to chemical analysis, for
      revealing the localised nature of the brown algal response to wounding.

PMID- 14716563
TI  - Nitric oxide is induced by wounding and influences jasmonic acid signaling in
      Arabidopsis thaliana.
AB  - Nitric oxide (NO) has been associated with plant defense responses during
      microbial attack, and with induction and/or regulation of programmed cell death.
      Here, we addressed whether NO participates in wound responses in Arabidopsis
      thaliana (L.) Heynh. Real-time imaging by confocal laser-scanning microscopy in
      conjunction with the NO-selective fluorescence indicator 4,5-diaminofluorescein
      diacetate (DAF-2 DA) uncovered a strong NO burst after wounding or after
      treatment with JA. The NO burst was triggered within minutes, reminiscent of the
      oxidative burst during hypersensitive responses. Furthermore, we were able to
      detect NO in plants (here induced by wounding) by means of electron paramagnetic
      resonance measurements using diethyldithiocarbamate as a spin trap. When plants
      were treated with NO, Northern analyses revealed that NO strongly induces key
      enzymes of jasmonic acid (JA) biosynthesis such as allene oxide synthase (AOS)
      and lipoxygenase (LOX2). On the other hand, wound-induced AOS gene expression was
      independent of NO. Furthermore, JA-responsive genes such as defensin (PDF1.2)
      were not induced, and NO induction of JA-biosynthesis enzymes did not result in
      elevated levels of JA. However, treatment with NO resulted in accumulation of
      salicylic acid (SA). In transgenic NahG plants (impaired in SA accumulation
      and/or signaling), NO did induce JA production and expression of JA-responsive
      genes. Altogether, the presented data demonstrate that wounding in Arabidopsis
      induces a fast accumulation of NO, and that NO may be involved in JA-associated
      defense responses and adjustments.

PMID- 14716564
TI  - Maternal synthesis of abscisic acid controls seed development and yield in
      Nicotiana plumbaginifolia.
AB  - The role of maternally derived abscisic acid (ABA) during seed development has
      been studied using ABA-deficient mutants of Nicotiana plumbaginifolia Viviani.
      ABA deficiency induced seed abortion, resulting in reduced seed yield, and
      delayed growth of the remaining embryos. Mutant grafting onto wild-type stocks
      and reciprocal crosses indicated that maternal ABA, synthesized in maternal
      vegetative tissues and translocated to the seed, promoted early seed development
      and growth. Moreover ABA deficiency delayed both seed coat pigmentation and
      capsule dehiscence. Mutant grafting did not restore these phenotypes, indicating
      that ABA synthesized in the seed coat and capsule envelope may have a positive
      effect on capsule and testa maturation. Together these results shed light on the
      positive role of maternal ABA during N. plumbaginifolia seed development.

PMID- 14716565
TI  - Domain structures of chlorophyllide a oxygenase of green plants and
      Prochlorothrix hollandica in relation to catalytic functions.
AB  - Chlorophyll b is a photosynthetic antenna pigment found in prochlorophytes and
      chlorophytes. In chlorophytes, its biosynthesis regulates the photosynthetic
      antenna size. Chlorophyll b is synthesized from chlorophyll a in a two-step
      oxygenation reaction by chlorophyllide a oxygenase (CAO). In this study, we first
      identified the entire sequence of a prochlorophyte CAO gene from Prochlorothrix
      hollandica to compare it with those from chlorophytes, and we examined the
      catalytic activity of the gene product. Southern blot analysis showed that the
      CAO gene is presented in one copy in the P. hollandica genome. The P. hollandica
      CAO gene (PhCAO) has a coding capacity for 367 amino acids, which is much smaller
      than that of Arabidopsis thaliana (537 amino acids) and Oryza sativa (542 amino
      acids) CAO genes. In spite of the small size, PhCAO catalyzed the formation of
      chlorophyll b. By comparing these sequences, we classified the land-plant
      sequences into four parts: the N-terminal sequence predicted to be a transit
      peptide, the successive conserved sequence unique in land plants (A-domain, 134
      amino acids), a less-conserved sequence (B-domain, 30 amino acids) and the C
      terminal conserved sequence common in chlorophytes and prochlorophytes (C-domain,
      337 to 344 amino acids). We demonstrated that the C-domain is sufficient for
      catalytic activity by transforming the cyanobacterium Synechocystis sp. PCC6803
      with the C-domain from A. thaliana. In this paper, the role of the A-domain is
      discussed in relation to the formation of light-harvesting chlorophyll a/b
      protein complexes in land plants.

PMID- 14716566
TI  - Graviperception in growth inhibition of plant shoots under hypergravity
      conditions produced by centrifugation is independent of that in gravitropism and
      may involve mechanoreceptors.
AB  - Hypergravity caused by centrifugation inhibits elongation growth of shoots by
      decreasing the cell wall extensibility via suppression of xyloglucan breakdown as
      well as by the thickening of cell walls. The mechanism of graviperception in
      hypergravity-induced growth inhibition was investigated in Arabidopsis [A.
      thaliana (L.) Heynh.] hypocotyls and azuki bean (Vigna angularis Ohwi et Ohashi)
      epicotyls. Hypergravity caused growth suppression in both sgr1-1 and pgm1, which
      are Arabidopsis mutants deprived of gravitropism, as in wild-type plants,
      suggesting that the graviperception in hypergravity-induced growth inhibition of
      shoots is independent of that in gravitropism. Hypergravity had no effects on
      growth of azuki bean epicotyls or Arabidopsis hypocotyls in the presence of
      lanthanum or gadolinium, which are blockers of mechanoreceptors. Moreover,
      lanthanum or gadolinium at the same concentration had no influence on
      gravitropism of azuki bean epicotyls and Arabidopsis hypocotyls. Hypergravity had
      no effects on cell wall extensibility and affected neither xyloglucan metabolism
      nor the thickness of cell walls in the lanthanum- or gadolinium-treated azuki
      bean epicotyls. Lanthanum or gadolinium inhibited the hypergravity-induced
      increase in the pH of the apoplastic fluid in the epicotyls, which is involved in
      the processes of the suppression of xyloglucan breakdown due to hypergravity.
      These findings suggest that plants perceive the hypergravity stimuli by
      mechanoreceptors in the plasma membrane, and utilize the perceived signal to
      regulate the growth rate of their shoots.

PMID- 14716567
TI  - [Sperm quality -- do neoplasms have an effect?].

PMID- 14716568
TI  - [Unilateral dilatation of the kidney. Which children profit from the procedure?].

PMID- 14716569
TI  - [Prostatic carcinoma. Zoledronic acid raises bone density].

PMID- 14716570
TI  - [Long-time survival after kidney transplantation. Main factors are age,
      histocompatibility and hypertension].

PMID- 14716571
TI  - [Gadolinium enhanced MRI . To unequivocally demonstrate acute polynephritis in
      children].

PMID- 14716572
TI  - [Radical cystectomy. Comparison of "Hautmann" and "Studer-neobladder"].

PMID- 14716573
TI  - [Vesicoureteral reflux. Waiting attitude as the initial measure is significant].

PMID- 14716575
TI  - [The PDA (Personal Digital Assistant) -- helpful to the urologist?].

PMID- 14716574
TI  - [Prognostic value of urodynamic testing in myelodysplastic patients].

PMID- 14716576
TI  - [Health care reform 2004. Consequences for the contract physician].

PMID- 14716578
TI  - [Prepayment on all hospital accounts. Hospitals challenged to fast reaction --
      the medical know-how decisive factor].

PMID- 14716579
TI  - Cellular basis for ST-segment changes observed during ischemia.
AB  - This study probes the cellular basis for ischemia-induced ST-segment elevation
      with the isolated arterially perfused canine ventricular wedge preparation.
      Transmembrane action potentials (AP) from epicardial (Epi) and endocardial (Endo)
      regions, a pseudo-electrocardiogram (ECG), and 5 intramural unipolar electrograms
      were simultaneously recorded at a basic cycle length of 800 or 2,000 ms. Global
      ischemia was induced by an abrupt interruption of coronary flow for 30 minutes.
      Under control conditions, the ST segment was isoelectric because of the absence
      of voltage gradients at the level of AP plateau among the cells spanning the
      ventricular wall. Global ischemia could cause an all-or-none repolarization at
      the end of phase 1 of the AP in Epi but not Endo leading to ST-segment elevation
      and extrasystolic activity secondary to phase 2 re-entry. In the majority of
      preparations, global ischemia resulted in a progressive increase in transmural
      conduction time after 25 to 30 minutes of interruption of flow caused by a step
      delay of impulse transmission in the midmyocardium. The ECG assumed a "tombstone"
      configuration. Correlation of the APs and ECG activity revealed that the apparent
      severe ST-segment elevation encountered under these conditions is actually a
      markedly prolonged R wave. In control, Endo repolarized after Epi yielding
      upright T waves in the ECG. After 30 minutes of ischemia Epi repolarized after
      Endo causing reversal of repolarization gradients and T-wave inversion. The
      ischemia-induced electrophysiologic changes returned to nearly control values
      within 5 minutes of reperfusion. Our results indicate that 2 distinctly different
      mechanisms involving 1) loss of the epicardial action potential dome and 2)
      markedly delayed transmural conduction underlie the apparent ST-segment elevation
      encountered during acute ischemia.

PMID- 14716580
TI  - Mechanisms of ST change in partial thickness ischemia.
AB  - The origin of ST depression in ischemia remains poorly understood. The accepted
      source is of intracellular current flowing between the ischemic and non ischaemic
      muscle both in systole and diastole such that the AC recorded electrocardiogram
      shows ST elevation over the ischemic area. The difficulty comes with partial
      thickness ischemia where the body surface changes do not allow localisation of
      the ischemic region. In an animal model we have shown that the reason one cannot
      see the region on the body surface is that the epicardial distribution of ST
      segment is almost identical for partial thickness ischaemia in the left anterior
      descending coronary artery, (LAD) and circumflex coronary artery (Cx)
      territories. Dissection of the reasons for this finding has lead to 3
      contributing factors. The first is the role of the right ventricular blood mass,
      the second the boundary between ischemia and normal and the third the presence of
      anisotropy and its contribution. In a block of myocardium with anisotropy
      included we have shown marked differences between the distributions depending on
      the anisotropy. We have also shown that the published values of conductivity for
      use in the bidomain model produce unacceptably disparate results.

PMID- 14716581
TI  - The supplementary effect of QRS changes on the inverse relationship between ST
      changes and salvage: testing the Sclarovsky/Birnbaum clinical method in the basic
      Jennings/Reimer model.
AB  - Acute complete occlusion of a major epicardial coronary artery typically causes
      sufficient ischemia in the dependent myocardial cells to produce the
      electrocardiogram change called "epicardial injury". There is sufficient shift of
      the ST baseline toward, and of the TP/PR baseline away from the involved region
      to provide the clinical diagnosis. Relationships between the quantities of this
      baseline shift and etiologic ischemia have previously been shown to provide
      clinical value. However, it has now become apparent that potentially reversible
      ischemia can be so severe, in the absence of protection from collaterals and/or
      ischemia preconditioning, that it alters myocardial conduction and the resultant
      QRS complexes. This report presents highlights from two studies in progress to
      determine the relative abilities of ST segment and QRS changes during coronary
      occlusion to predict salvage following reperfusion; and the relative effects of
      collaterals and ischemia preconditioning to produce each of these
      electrocardiogram changes.

PMID- 14716582
TI  - Quantitative assessment of myocardial ischemia by electrocardiographic and
      scintigraphic imaging.
AB  - We calculated distributions of epicardial potentials from body-surface
      electrocardiograms (ECGs) recorded during controlled myocardial ischemia and
      compared them with scintigraphic estimates of ischemia's extent/severity. The
      study population consisted of patients suffering from single-vessel coronary
      artery disease, referred for elective percutaneous transluminal coronary
      angioplasty of either the left anterior descending (n=7), the right coronary
      (n=9), or the left circumflex (n=2) artery. After the target vessel had been
      dilated, a 1960s "study" inflation was performed with a non-perfusion-type
      balloon catheter; at its commencement, technetium-99m sestamibi was injected via
      a femoral-vein catheter, and ECGs were recorded throughout the inflation from 120
      leads. Single photon emission computed tomographic imaging was performed one hour
      after the injection of radionuclide to obtain an "occlusion image", and again one
      hour after a repeat injection 24 hours later to obtain a "control image"; the
      latter image was subtracted from the former, to derive a scintigraphic difference
      map (Delta map). The ECGs were signal-averaged over a 10-s window at preinflation
      and peak-inflation states, the preinflation averaged complexes were subtracted
      from the peak-inflation ones to produce body-surface Delta maps, and the
      corresponding Delta maps of epicardial potentials were calculated by applying the
      electrocardiographic inverse solution; this procedure is referred to as
      electrocardiographic imaging. The ECG-derived epicardial Delta maps related
      spatially to the scintigraphic Delta maps in all patients. The percent areas and
      surface integrals of positive values in ECG-derived Delta maps were found to be
      very good single-variable predictors of the extent (r=0.73; p=0.0006) and
      severity (r=0.72; p=0.0008) of the scintigraphically-estimated perfusion defect;
      a regression equation using two ECG-derived predictors further improved the
      agreement with scintigraphic estimates (r=0.81; p=0.0004 for estimates of
      severity). These findings suggest that noninvasive electrocardiographic imaging
      might provide quantitative estimates of the extent/severity of myocardial
      ischemia that agree closely with those provided by scintigraphic techniques.

PMID- 14716583
TI  - The infarct Q wave: foretaste and aftertaste; presentiment and recall.
AB  - Since acute myocardial infarction involves a progressive disturbance of
      intramyocardial propagation the process might be regarded as a conduction
      disturbance: incomplete in the evolving phase; complete with Q wave inscription.
      Premature atrial excitation (PAE) can induce fascicular or bundle branch
      conduction delay, or complete functional block. Considered here are the concepts
      of foretaste: in which PAE reveals the infarct Q before it has appeared in
      regular sinus beats, and aftertaste: in which, following the healing of the
      myocardial infarction, the Q wave is recalled by PAE after it has disappeared
      from regular beats. Foretaste was observed in a small number of acutely infarcted
      dogs. Aftertaste is substantially more problematic since Q wave inscription is
      known to occur, however uncommonly, in a small minority of noninfarcted
      aberration morphologies. Only lateral infarct Q waves appear to be recallable by
      PAE.

PMID- 14716591
TI  - From myocardial cell models to action potential propagation.
AB  - Membrane equations that describe sarcolemmal currents and ion transfer processes
      are important building blocks for theoretical studies of action potential
      propagation in cardiac tissue. Introduction of such ionic models into cellular
      and tissue networks allows analyses of passive contributions associated with
      tissue structure to be considered alongside active contributions from myocytes
      themselves in studies involving arrhythmia initiation, maintenance and
      termination. Maturation of contemporary membrane equations that attempt to
      replicate voltage clamp experiments from different species and tissue types with
      specific examples of modifications to extend those equations for simulations
      under conditions of rapid pacing, myocardial ischemia and remodeling following
      myocardial infarction are considered. Additionally, the integrating of membrane
      equations into models where coupling to represent current flow paths associated
      with the anisotropic tissue structure is described.

PMID- 14716592
TI  - Upper limit of vulnerability in a defibrillation model of the rabbit ventricles.
AB  - The goal of this modeling study is to investigate the mechanisms responsible for
      the upper and lower limits of vulnerability (ULV and LLV) to re-entry induced by
      electric shocks within the three-dimensional volume of the heart. We use a
      geometrically accurate rabbit ventricular model with realistic fiber architecture
      that also includes the blood in the cavities and a perfusing bath. The shocks are
      delivered over a range of strengths and coupling intervals via two large mesh
      electrodes located at the vertical boundaries of the perfusing bath. Our results
      demonstrate that shock-induced virtual electrode polarization (VEP) in the
      midmyocardium is weaker and more complex than VEP on the surfaces, where only 2
      areas, one of positive and one of negative polarization, are induced. Transmural
      views of the ventricles show that, in all cases, tissue in the LV free wall and
      in the septum is deexcited by the shock providing an excitable path for wavefront
      propagation. Conversely, the RV free wall myocardium is depolarized after the end
      of the shock. The evolution of postshock electrical activity in the RV free wall
      plays a critical role in determining the outcome of the shock. In all cases, a
      wavefront starts in the apex at the site of largest transmembrane voltage
      gradient between oppositely polarized areas. For shocks of strength above the
      LLV, the postshock refractoriness of the RV free wall produces the unidirectional
      block necessary for reentry induction. If shock strength is below the ULV, the RV
      free wall recovers in time to provide the reentrant pathway. In contrast, for
      shocks of strength above the ULV, the postshock excitable gap in the LV free wall
      and in the septum is depolarized before the RV free wall recovers. Therefore,
      both ventricles are refractory and reentry is not induced

PMID- 14716593
TI  - Electromechanical model of cardiac resynchronization in the dilated failing heart
      with left bundle branch block.
AB  - Experimental studies have shown that biventricular pacing can improve systolic
      function in the failing heart with bundle branch block. The goal of this study
      was to develop and validate a three-dimensional computational model of the
      dilated failing heart with left bundle branch block to investigate how
      biventricular pacing can improve systolic mechanical performance and synchrony.
      In an anatomically detailed model of canine ventricular geometry, fiber
      architecture and Purkinje fiber network structure, a monodomain solution for
      anisotropic impulse conduction gave rise to electrical activation sequences that
      were consistent with experimentally observed patterns. Coupling this with
      regional myocardial mechanics computed for left branch bundle block and
      biventricular pacing showed good agreement with published regional fiber strains
      measured in dogs by using magnetic resonance imaging tagging. Biventricular
      pacing improved mechanical synchrony and systolic function in the computational
      model. The model may be a useful tool for investigating the pacing conditions
      required to achieve optimal mechanical improvement in the failing heart,
      especially because electrical synchrony does not correlate directly with
      mechanical synchrony and performance.

PMID- 14716594
TI  - Cardiac electrical activity--from heart to body surface and back again.
AB  - We report here on our latest developments in the forward and inverse problems of
      electrocardiology. In the forward problem, a coupled cellular model of cardiac
      excitation-contraction is embedded within an anatomically realistic model of the
      cardiac ventricles, which is itself embedded within a torso model. This continuum
      modelling framework allows the effects of cellular-level activity on the surface
      electrocardiogram (ECG) to be carefully examined. Furthermore, the contributions
      of contraction and local ischemia on body surface recordings can also be
      elucidated. Such information can provide theoretical limits to the sensitivity
      and ultimately the detection capability of body surface ECG recordings. Despite
      being very useful, such detailed forward modelling is not directly applicable
      when seeking to use densely sampled ECG information to assess a patient in a
      clinical environment (the inverse problem). In such a situation patient specific
      models must be constructed and, due to the nature of the inverse problem, the
      level of detail that can be reliably reproduced is limited. Extensive simulation
      studies have shown that the accuracy with which the heart is localised within the
      torso is the primary limiting factor. To further identify the practical
      performance capabilities of the current inverse algorithms, high quality
      experimental data is urgently needed. We have been working towards such an
      objective with a number of groups, including our local hospital in Auckland. At
      that hospital, in patients undergoing catheter ablation surgery, up to 256
      simultaneous body surface signals were recorded by using various catheter pacing
      protocols. The geometric information required to customize the heart and torso
      model was obtained using a combination of ultrasound and laser scanning
      technologies. Our initial results indicate that such geometric imaging modalities
      are sufficient to produce promising inversely-constructed activation profiles.

PMID- 14716595
TI  - Computational tools for modeling electrical activity in cardiac tissue.
AB  - Computer models offer many attractive benefits. However, the modeling of cardiac
      tissue is computationally expensive due to several physical constraints which
      result in fine spatiotemporal discretization over large spatiotemporal regions.
      Our laboratory has been actively trying to develop new techniques to make large
      scale cardiac simulations tractable over the past 15 years. This paper describes
      the latest modeling software that our group has developed, called Carp (Cardiac
      arrhythmias research package). It is designed to run in both shared memory and
      clustered computing environments. Carp aims to be modular and flexible by
      following a plug-in framework. This allows the latest models and most efficient
      solvers to be incorporated as well as enabling run-time selection of techniques.
      Performance results are given for a large-scale simulation which utilized a
      comprehensive membrane ionic current description.

PMID- 14716596
TI  - T-wave alternans: marker, mechanism, and methodology for predicting sudden
      cardiac death.
AB  - Sudden cardiac death (SCD) is a leading cause of cardiovascular mortality.
      Therefore, identifying patients at highest risk for SCD is crucial. Conventional
      noninvasive markers of SCD are inadequate because of low positive predictive
      value. The presence of visible T-wave alternans (TWA) on electrocardiogram often
      predicts the occurrence of lethal ventricular arrhythmias. Signal processing
      methods have made it possible to detect microvolt-level and visually inapparent
      TWA on electrocardiogram. TWA is caused by underlying regional inhomogeneities of
      ventricular repolarization, which predispose patients to have ventricular
      arrhythmias. Microvolt TWA provoked either by atrial pacing, pharmacological
      stress, or exercise is a promising marker of arrhythmia vulnerability. Several
      large trials have shown TWA to be comparable or superior to other noninvasive
      markers and electrophysiologic study in the prediction of SCD. The patient
      populations in these trials include post myocardial infarction, both ischemic and
      nonischemic heart failure, and suspected arrhythmias. Prospective trials
      regarding benefits of implantation of cardioverter-defibrillator therapy based on
      TWA results are ongoing.

PMID- 14716597
TI  - QT variability.
AB  - We hypothesized that temporal lability in ventricular repolarization is a marker
      for, and is mechanistically related to, increased risk of malignant ventricular
      arrhythmias. To assess repolarization lability in the surface electrocardiogram,
      we developed an automated algorithm, based on template matching, to measure beat
      to-beat changes in QT interval. We calculate a QT variability index (QTVI) to
      quantify the relative magnitude of QT interval changes compared to heart rate
      variability. We found that QTVI is a reproducible measure. It is elevated in
      patients with ischemic and nonischemic dilated cardiomyopathy compared with age
      matched controls (P<.00001). We have also shown that QTVI is elevated in patients
      with malignant beta-myosin heavy-chain mutations associated with hypertrophic
      cardiomyopathy. In a study of patients undergoing electrophysiologic testing,
      QTVI identified patients with cardiac arrest better than electrophysiologic test
      result and better than other risk stratifiers included in the analysis. QT
      variability is a marker of electrical disease in the ventricle and may be
      associated with enhanced risk of life-threatening arrhythmias.

PMID- 14716598
TI  - Heart rate turbulence.
AB  - Survivors of acute myocardial infarction are at increased risk of sudden cardiac
      death. Recent trials have demonstrated that in selected high risk post-myocardial
      infarction patients mortality can be significantly reduced by implantation of an
      autonomic cardioverter defibrillator. Therefore, risk stratification strategies
      have gained increasing importance. Recently, a new method for risk
      stratification, coined heart rate turbulence, has been published. The method
      quantifies the physiological short term fluctuation of sinus rhythm cycle lengths
      following singular ventricular premature complexes. Heart rate turbulence is a
      consistent phenomenon in low risk patients with ischemic heart disease. The
      absence of this phenomenon indicates a significantly increased risk of subsequent
      mortality. The measures for quantifying heart rate turbulence, turbulence onset,
      and turbulence slope are strong risk predictors, even when adjusted for other
      established mortality predictors, such as left ventricular ejection fraction,
      arrhythmia count, heart rate variability, mean heart rate and history of previous
      myocardial infarction. Heart rate turbulence may be useful not only for risk
      prediction in post-myocardial infarction patients but also for risk prediction in
      other patients such as in patients with dilated cardiomyopathy and Chagas
      disease.

PMID- 14716599
TI  - Measurement of heart rate variability by methods based on nonlinear dynamics.
AB  - Heart rate (HR) variability has been conventionally analyzed with time and
      frequency domain methods, which measure the overall magnitude of R-R interval
      fluctuations around its mean value or the magnitude of fluctuations in some
      predetermined frequencies. Analysis of HR dynamics by methods based on chaos
      theory and nonlinear system theory has gained recent interest. This interest is
      based on observations suggesting that the mechanisms involved in cardiovascular
      regulation likely interact with each other in a nonlinear way. Furthermore,
      recent observational studies suggest that some indexes describing nonlinear HR
      dynamics, such as fractal scaling exponents, may provide more powerful prognostic
      information than the traditional HR variability indexes. In particular, short
      term fractal scaling exponent measured by detrended fluctuation analysis method
      has been shown to predict fatal cardiovascular events in various populations.
      Approximate entropy, a nonlinear index of HR dynamics, which describes the
      complexity of R-R interval behavior, has provided information on the
      vulnerability to atrial fibrillation. There are many other nonlinear indexes, eg,
      Lyapunov exponent and correlation dimensions, which also give information on the
      characteristics of HR dynamics, but their clinical utility is not well
      established. Although concepts of chaos theory, fractal mathematics, and
      complexity measures of HR behavior in relation to cardiovascular physiology or
      various cardiovascular events are still far away from clinical medicine, they are
      a fruitful area for future research to expand our knowledge concerning the
      behavior of cardiovascular oscillations in normal healthy conditions as well as
      in disease states.

PMID- 14716600
TI  - Noninvasive risk stratification in postinfarction patients with severe left
      ventricular dysfunction and methodology of the MADIT II noninvasive
      electrocardiology substudy.
AB  - Sudden cardiac death occurs as a result of a complex interplay of changes in
      myocardial substrate, imbalance of autonomic regulation of the heart, and
      myocardial vulnerability. Noninvasive electrocardiology serves as a comprehensive
      tool for investigating factors representing mechanistic pathways leading to
      cardiac events. Heart rate variability, nonlinear dynamics of heart rate, and
      heart rate turbulence provide insight into autonomic control of the heart.
      Prognostic value of these parameters in postinfarction patients is well
      established for predicting cardiac death, but there is less evidence for their
      association with sudden death or arrhythmic events. Electrical manifestation of
      changes in myocardial substrate include QRS and QTc prolongation, presence of
      conduction disturbances, presence of late potentials, abnormalities of
      repolarization morphology, and presence of nonsinus rhythm, namely atrial
      fibrillation. Electrocardiogram (ECG) measures reflecting myocardial
      vulnerability to arrhythmias include frequent ventricular premature beats, T wave
      alternans, or QT variability. Prognostic significance of these parameters is
      documented in studies focused mostly on them as individual markers of risk. The
      noninvasive electrocardiology substudy of the Multicenter Automatic Defibrillator
      Implantation Trial II (MADIT II) allows for simultaneous analysis of several of
      the above ECG markers of risk and will provide insight about relative
      contribution of mechanistic pathways leading to cardiac death in postinfarction
      patients with severe left ventricular dysfunction. Combination of a standard 12
      lead ECG and 10-minute high-resolution Holter recordings serves to evaluate the
      prognostic significance of noninvasive electrocardiology parameters for mortality
      in patients randomized to conventional treatment and for arrhythmic events in
      patients randomized to implantable cardioverter defibrillator therapy.

PMID- 14716610
TI  - Spatial QRS-T angle as a risk indicator of cardiac death in an elderly
      population.

PMID- 14716611
TI  - Identification of sotalol-induced changes in repolarization with T wave area
      based repolarization duration parameters.
AB  - In this study, we investigated the validity of T wave area-based parameters for
      the identification of drug-induced changes of repolarization. Based on
      electrocardiograms from 39 healthy patients, we computed the stability of
      repolarization measurements and compared the sotalol-induced repolarization
      changes when measured with area-based parameters and traditional QT interval
      techniques (manual and automatic). Also, we evaluated the effect of different
      types of heart rate correction on these repolarization measurements. The results
      show that the stability of the automatic repolarization measurements is higher
      when measured using computer algorithm than using manual QT measurement. By using
      a population-based heart rate correction, the area-based parameters reveal
      significant modification of the overall shape of the T wave in its early, middle,
      and final part. In conclusion, morphological parameters of T wave are able to
      identify the changes in repolarization interval induced by sotalol. These
      parameters are more stable and thus more reliable than the traditional QT
      interval measurements.

PMID- 14716612
TI  - Risk stratification in diabetic patients with a previous myocardial infarction.
AB  - We used Kaplan-Meier 2-year survival analysis on CAST registry patients to
      estimate prognostic power of VPC frequency (> or =10/hr), presence of
      nonsustained ventricular tachycardia (NSVT), left ventricular ejection fraction,
      and presence of diabetes. We also used meta-analysis of reports in the literature
      to estimate prognostic power of signal-averaged electrocardiogram (SAECG) and
      electrophysiological tests (EPS) as well as VPCs, NSVT, and LVEF. Combined
      results from CAST analysis and literature meta-analysis yielded sensitivity and
      specificity for VPCs, NSVT, SAECG, LVEF, Diabetes, and EPS. The overall 2 year
      event rate for life-threatening arrhythmias or death was 7.88% for 51,144 cases
      in the combined CAST and literature data. After segmenting the population 21.3%
      were diabetic with a predicted 2 yr event rate of 13.5% and 78.7% were
      nondiabetic event rate of 6.4%. We defined low risk as <10% and high risk as > or
      =30%. Otherwise predicted event rate was classified as "unstratified." When all
      possible combination of noninvasive tests were applied, a prominent difference in
      the proportions of cases at risk between the diabetics and nondiabetics was
      revealed. When the unstratified cases were subsequently tested with EPS, the
      difference between the two groups was even more marked.

PMID- 14716613
TI  - The use of calculated epicardial potentials improves significantly the
      sensitivity of a diagnostic algorithm in the detection of acute myocardial
      infarction.
AB  - Inverse electrocardiography can calculate epicardial potentials (EP) from body
      surface potentials (BSP) taking into account a thoracic volume conductor model
      (TVCM). Previous studies have shown that a tailored TVCM is superior to a general
      TVCM in calculating EP. However, construction of a tailored TVCM for a patient in
      an acute clinical setting is impractical. In this study we used a general TVCM in
      our EP calculations to determine whether this improves detection of acute
      myocardial infarction (AMI) using a diagnostic algorithm. BSP were derived from
      the 80-lead body surface map (BSM). Consecutive patients (n=379) with ischemic
      type chest pain were recruited. The BSM and a 12-lead electrocardiogram (ECG)
      were recorded at initial presentation and creatine kinase (CK) and/or CK-MB were
      measured initially, 12 and 24 hours postsymptom onset. A physician interpreted
      the 12-lead electrocardiogram and documented ST elevation if present. AMI was
      defined by the World Health Organization (WHO) criteria. The diagnostic algorithm
      result for each patient using BSP and calculated EP were documented. AMI occurred
      in 171 patients. The diagnostic algorithm using BSP identified 106 of these as ST
      elevation AMI (STEMI) (sensitivity 62%, specificity 80%). The same algorithm
      using EP identified 133 as STEMI (sensitivity 78%, specificity 80%). Calculated
      EP improved the algorithm's diagnostic sensitivity by a factor of 1.25 (P<.001)
      with no significant difference in specificity. Calculated EP using a general TVCM
      significantly improves the sensitivity of a diagnostic algorithm based on BSP in
      detection of AMI with no significant loss in specificity.

PMID- 14716614
TI  - The elusive U wave: a simple explanation of its genesis.
AB  - Of the various waveforms in the electrocardiogram (ECG), the U wave has been the
      most elusive. After the first description of a U wave by Einthoven several
      hypotheses were put forward as to its origin. Three of these are frequently
      quoted, ie: 1) the repolarization of the Purkinje fibres; 2) the prolonged
      repolarization of the M-cells in the midmyocardium; and 3) after-potentials,
      possibly caused by mechanical forces in the ventricular wall. However, none of
      these hypotheses has gained general acceptance. We present a simple multilayered
      digital model of the myocardium, which explains the formation of the U wave on
      the basis of known electrophysiological processes responsible for the electrical
      sources in the myocardium, and of the physical laws, formulated in the lead
      vector concept, which link the potentials in or on the body to these sources. A
      realistic action potential (AP) is assigned to each layer. The timing of the APs
      is such that a normal ventricular wall activation is simulated. The differences
      in APs between adjacent layers create current sources Di that contribute to the
      potential course at an arbitrary observation point P through the heart vector
      lead vector relationship. Assuming a homogeneous infinite medium, without
      changing the AP shapes or durations and without introducing after potentials,
      different realistically shaped T and U waves are simulated. Their amplitudes and
      configurations are dependent on the value of L, viz. the relative distance of the
      observation point to the myocardium. The gradual and varying transition from T
      wave into the U brings into question the traditional view that the end of T wave
      represents the end of the myocardial repolarization: T and U together must be
      considered as one repolarization complex. The traditional concept of QT
      prolongation would then need revision.

PMID- 14716615
TI  - PhysioNet: an NIH research resource for complex signals.
AB  - The Research Resource for Complex Physiologic Signals, supported by the National
      Institutes of Health (NIH), is intended to promote and facilitate investigations
      in the study of cardiovascular and other complex biomedical signals. The resource
      website (www.physionet.org) has 3 interdependent components: 1) PhysioBank is an
      archive of well-characterized digital recordings of physiologic signals and
      related data, including databases of electrocardiogram and heart rate time series
      from patients with heart failure, coronary disease, sleep apnea syndromes, and
      cardiac arrhythmias; 2) PhysioToolkit is a library of open-source software for
      physiologic signal processing and analysis; and 3) PhysioNet, for which the
      resource is named, is an on-line forum for dissemination and exchange of recorded
      biomedical signals and open-source software for analyzing them. PhysioNet, in
      cooperation with the annual Computers in Cardiology conference, hosts a series of
      challenges inviting participants to tackle clinically interesting problems that
      are either unsolved or not well solved. PhysioNet invites contributions of
      databases and software from the biomedical community.

PMID- 14716616
TI  - Development of a new QT algorithm with heterogenous ECG databases.
AB  - An algorithm for automated QT interval assessments has been developed and
      evaluated using the PhysioNet QT database and the electrocardiogram multilead
      database (2 collections of electrocardiograms with different characteristics, eg,
      numbers of leads and expert annotations). QRS onset and coarse T offset detection
      was based on the definition of a short time window, within which the range of
      signal amplitudes was calculated and compared to given threshold values. The
      final position of T offset was based on a combination of 3 methods: decreasing
      thresholds, multiple tangents, and a model based approach. The evaluation was
      based on the comparison of a waveform marker as computed automatically, and those
      of the human experts. Mean and standard deviation of those differences compared
      well to other algorithms and to inter-expert variations. Waveform marker
      detection was successful in at least 98% of the annotated beats in both
      databases, thus, indicating the robustness of the proposed method.

PMID- 14716617
TI  - State of the art techniques for preservation and reuse of hard copy
      electrocardiograms.
AB  - Baseline examinations and periodic reexaminations in longitudinal population
      studies, together with ongoing surveillance for morbidity and mortality, provide
      unique opportunities for seeking ways to enhance the value of electrocardiography
      (ECG) as an inexpensive and noninvasive tool for prognosis and diagnosis. We used
      newly developed optical ECG waveform recognition (OEWR) technique capable of
      extracting raw waveform data from legacy hard copy ECG recording. Hardcopy ECG
      recordings were scanned and processed by the OEWR algorithm. The extracted ECG
      datasets were formatted into a newly proposed, vendor-neutral, ECG XML data
      format. Oracle database was used as a repository for ECG records in XML format.
      The proposed technique for XML encapsulation of OEWR processed hard copy records
      resulted in an efficient method for inclusion of paper ECG records into research
      databases, thus providing their preservation, reuse and accession.

PMID- 14716618
TI  - Arrhythmia database for algorithm testing: surface leads plus intracardiac leads
      for validation.
AB  - Ann Arbor Electrogram Libraries (AAEL) is a database of over 500
      electrocardiographic recordings made during clinical electrophysiology studies
      over a period of 15 years. These data are used by university researchers and
      cardiac device research and development laboratories to develop and test
      arrhythmia detection algorithms. The AAEL library is in use by all major
      implantable cardioverter defibrillator manufacturers as well as several Automated
      External Defibrillator developers. In 1996, the USFDA Center for Devices and
      Radiological Health licensed a portion of Volumes I for proposed device testing.
      The data consist of 7 channels of signals: surface leads I, III, V1, an intra
      atrial high right atrium (bipolar), an intra-atrial high right atrium (unipolar),
      an intraventricular right ventricular apex (bipolar), and intraventricular right
      ventricular apex (unipolar) from the distal catheter electrode. Data were
      recorded under careful engineering quality control continuously (30 min-1.5 hr)
      on FM magnetic tape at a tape speed of 3.75 in/s after signal amplification at a
      filter setting of 1-500 Hz. Amplifier gain and filter settings were held constant
      during the entire recording procedure and a 1 mV calibration signal was entered
      as a reference at the time of recording. All patient recordings contain a
      baseline sinus rhythm, and subsequently induced ventricular tachycardia and/or
      ventricular fibrillation, or less frequently, supraventricular tachycardia,
      atrial tachycardia, and/or atrial fibrillation. Data are typically made available
      in digitized format (1,000 Hz); digital or FM recordings are also available. AAEL
      recordings are the only widespread intracardiac test files in the industry.

PMID- 14716619
TI  - Overview of the ISCE ECG "genome project".
AB  - The International Society for Computerized Electrocardiography (ISCE) "genome"
      project was begun at the end of 2000 to explore mechanisms for development of a
      cross-platform electrocardiogram (ECG) database. Ultimate feasibility of this
      project is based on established interactive cooperation of clinical
      investigators, engineers, and industry within the ISCE framework. The US Food and
      Drug Administration (FDA) mandate for centralized access to digitized ECG
      waveforms used in clinical trials provides a complementary stimulus to
      technologies that facilitate ECG database development. The constituency of ISCE
      is interested in acquisition and analysis of data from both standard 12-lead
      (resting) ECG and ambulatory (monitoring) ECG. Support for project goals from
      industry, at the Trustee as well as at the engineering level, has led to initial
      focus on the resting ECG. A one-year pilot project has been proposed to establish
      and implement software methodology for transmission, storage, and integrated
      reanalysis of digitized ECG waveforms provided by several major manufacturers.
      Beyond data acquisition, storage, and analysis, a number of critical issues are
      associated with database development. These include definition of clinically
      relevant "gold" standards, acquisition and validation of non-ECG data, protection
      of patient privacy, control and ownership of data, and accessibility and use of
      the database. However, implementation of the pilot project is a necessary first
      step, since all issues become moot without technical cooperation for shared
      formatting and analysis.

PMID- 14716630
TI  - Atrial flutter vector loops derived from the surface ECG: does the plane of the
      loop correspond anatomically to the macroreentrant circuit?
AB  - We hypothesized that if the right atrial circuit during isthmus dependent atrial
      flutter provides the dominant contribution to the surface electrocardiogram
      (ECG), the three-dimensional vector loop of the flutter waves would primarily be
      in a plane approximately parallel to the tricuspid ring. Twenty vectorcardiograms
      of isthmus dependent atrial flutter derived from 12-lead ECGs of 19 patients
      recorded prior to radiofrequency ablation were analyzed. The plane of each loop,
      described by azimuth and elevation angles relative to the frontal plane, was
      estimated with two methods: 1) plane of maximum loop area and 2) plane of best
      fit. The plane of maximum loop of the loops had mean azimuth of -58 +/- 37
      degrees. and elevation of 15 +/- 15 degrees. The plane of best fit of the loops
      had mean azimuth of -50 +/- 46 degrees and elevation of 15 +/- 14 degrees. Thus,
      clinical implications include the potential to predict atrial flutter mechanisms
      prior to intracardiac mapping.

PMID- 14716629
TI  - Cellular and ionic basis for the sex-related difference in the manifestation of
      the Brugada syndrome and progressive conduction disease phenotypes.
AB  - The Brugada syndrome (BS) has been linked to mutations in SCN5A. Despite equal
      hereditary transmission of the mutation between the sexes, the syndrome is 8 to
      10 times more likely to occur in males. As recently reported, SCN5A mutations
      such as G1406R lead to development of BS phenotype principally in males and
      conduction disease phenotype in females. We hypothesized that these differences
      may be related to a larger transient outward current (Ito)-mediated right
      ventricular (RV) epicardial (Epi) action potential (AP) notch in males versus
      females, resulting in a higher incidence of all-or-none repolarization at the end
      of phase 1 and phase 2 re-entry (P2R) when challenged with sodium and calcium
      channel block. Using canine RV wedge preparations, we developed an experimental
      model of the BS using terfenadine to depress the AP dome in RV Epi. RESULTS: RV
      Epi AP phase 1 amplitude corrected to phase 2 amplitude was 12% smaller in males
      (n=18) compared to females (n=8, P<.05) at a cycle length of 2,000 ms. When
      exposed to 5 microM terfenadine for up to 2 hours, 6 of 7 male but only 2 of 7
      female preparations exhibited spontaneous P2R, generating a closely coupled
      extrasystole. Two of 6 male and 1 of 2 female preparations displaying P2R
      developed polymorphic VT/VF. Female and male preparations that failed to develop
      P2R displayed progressive conduction impairment with continued exposure to
      terfenadine and developed polymorphic and monomorphic VT/VF when paced at rapid
      rates. Male preparations pretreated with 4-aminopyridine to inhibit Ito displayed
      progressive conduction impairment but not Brugada syndrome. CONCLUSION: Our data
      suggest that the presence of a more prominent Ito-mediated notch in the Epi of
      males predisposes males to the development of the Brugada phenotype and that a
      smaller Epi notch in females relegates them to development of progressive
      conduction problems under conditions in which inward currents are compromised.

PMID- 14716631
TI  - Estimation of the QT/RR hysteresis lag.
AB  - The process of QT interval adaptation to heart rate (HR) changes was evaluated by
      considering weighted averages of RR intervals to characterize the influence of
      previous cardiac cycles. An optimum adaptation pattern was individually derived
      for each patient and several descriptors of the QT/RR hysteresis were
      subsequently calculated. The values of these parameters showed that the QT
      adaptation to HR changes is highly individual and, consequently, any generalized
      approach may lead to inappropriate conclusions.

PMID- 14716632
TI  - Transvenous cardioversion--a novel asymmetric rectangular biphasic waveform from
      a radiofrequency defibrillator compared with conventional waveforms in atrial
      fibrillation.
AB  - BACKGROUND: We investigated a novel device that delivered biphasic and monophasic
      shocks without tilt, in transvenous cardioversion of atrial fibrillation (AF).
      The device contains a radiofrequency (RF) transmitting primary, a 15mm air gap
      and a passive secondary unit that produces the required direct current waveform.
      METHODS: The device was assessed in 10 anaesthetised and ventilated sheep (65 +/-
      SD 12kg). Defibrillation leads were positioned in the distal coronary sinus and
      the lateral right atrium. The novel RF defibrillator was assessed using
      rectangular monophasic or biphasic pulses and compared to conventional (C) tilted
      waveforms (Ventritex HVS-02). During AF placebo shocks were delivered to a 50
      Omega dummy load. Sustained AF was induced by rapid atrial pacing and 5 attempts
      at cardioversion were made for each waveform. Success was defined as reversion to
      sinus rhythm within 5 beats of shock delivery. RESULTS: No arrhythmic
      complications were observed for the 400 shocks delivered. CONCLUSION: A reduction
      in phase 2 voltage does not affect the efficacy of rectangular waveforms but does
      facilitate energy reduction. Asymmetric rectangular biphasic waveforms with phase
      2 voltage at 50% of phase 1 are more efficacious than equivalent voltage
      conventional waveforms for transvenous cardioversion of AF. The novel
      defibrillator is safe and effective. Design modifications will enable this device
      to be used as an implantable defibrillator with an external RF power source.

PMID- 14716633
TI  - Ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.
AB  - Experimental and clinical studies indicate a basic linkage between T-wave
      alternans (TWA) and susceptibility to malignant arrhythmias. In a variety of
      clinical populations with elevated risk of ventricular tachyarrhythmias, Fast
      Fourier Transform (FFT)-based assessment of TWA during fixed-rate atrial pacing
      or bicycle ergometry has shown predictive ability for arrhythmic events. However,
      after more than a decade since the introduction of TWA testing in human subjects,
      few studies have explored its utility in ambulatory ECG (AECG) recordings. This
      gap probably relates to major technical obstacles associated with monitoring of
      ambulatory subjects, including motion artifact and the requirement of data
      stationarity, which mandates fixing heart rate. To circumvent these difficulties,
      we devised a time-domain method, "Modified Moving Average Beat Analysis" (MMA) to
      determine TWA level accurately in freely moving subjects. Recently, MMA analysis
      was employed to analyze ambulatory ECG (AECG) records of post-myocardial
      infarction patients who were were at low risk of arrhythmic death. An increased
      risk of arrhythmic death was predicted by TWA level above the 75th percentile of
      controls (p<.05). Thus, the predictive power of TWA obtained with MMA analysis
      from AECG records obtained appears promising.

PMID- 14716634
TI  - Analysis of complex T-wave oscillations for prediction of ventricular
      fibrillation.
AB  - Increased attention has been focused on oscillatory behavior of the T wave as a
      manifestation of heightened electrical instability and risk for ventricular
      fibrillation (VF). This interest has stemmed from an increasing number of
      experimental and clinical studies indicating that the relatively simple ABAB
      oscillation of T-wave alternans (TWA) can be quantified to assess risk for
      arrhythmias. However, an important unanswered question is whether TWA represents
      the initial phase of a stepwise progression to higher-order oscillations that
      culminate in sudden arrhythmic death. Signals were analyzed from epicardial and
      endocardial ECGs from anesthetized dogs subjected to LAD coronary artery
      occlusion during fixed-rate atrial pacing. Our study was the first to demonstrate
      a stepwise increase in complexity of T-wave oscillations from TWA to T-wave
      tripling and quadrupling and to more complex forms just prior to onset of VF
      (Circ Res 2002;91:727-732). Discordant T-wave episodes, when T waves alternated
      out-of-phase, were found to be associated with increases in T-wave complexity and
      VF. None of the animals that failed to fibrillate exhibited discordant TWA. In
      these observations, complexity of T-wave oscillations points to a fundamental
      mechanistic link underlying the ability of TWA to predict lethal arrhythmias.

PMID- 14716636
TI  - Repolarization analysis in children with the long QT syndrome.
AB  - QT duration changes were analysed in 26 children with long QT syndrome (median
      age 9 years). With 12-lead Holter recordings, we found that macroscopically QT
      adaptation to heart rate changes was slow and only 3 of 26 patients showed abrupt
      changes in QT interval duration. These changes in the time domain were always
      accompanied by changes of STT morphology in the 3 of 26 patients. Application of
      Bazett's heart rate correction algorithm was inappropriate to show true QT
      changes in this young patient group due to temporary typical large cycle length
      variations, where moreover an overcorrection of the heart rate impact resulted in
      reflection of RR interval changes rather than true QT duration changes.

PMID- 14716635
TI  - Cycle length sequence dependent repolarization dynamics.
AB  - Cardiac repolarization, particularly its heterogeneity, is known to play a
      significant role in arrhythmogenesis. Steepness of cardiac restitution, or the
      cycle length dependency of repolarization, has also been implicated as a
      condition that favors occurrence of reentrant arrhythmias. However, most
      assessments of heterogeneity and restitution are based on static observations and
      do not directly account for the extent or heterogeneity of dynamic changes. The
      uncertainty and unpredictability of arrhythmias and the difficulty of identifying
      patients most at risk may possibly be explained by the lack of consideration of
      dynamic changes of repolarization, its heterogeneity and time varying
      restitution. In this brief article, we show the global changes in repolarization
      that occur in normal canine hearts in response to programmed cycle length
      sequences. Specifically, we show the beat-to-beat tracking of repolarization
      during rapid (step) changes in cycle length as well as linear up and down
      (sawtooth) changes, and random cycle length sequences. The measurement and robust
      characterization of the dynamic repolarization response to specific cycle length
      sequences may offer an opportunity to characterize the substrate for arrhythmias
      to a greater extent than has been possible to date. Although there is no
      guarantee that characterization of repolarization dynamics will provide
      definitive means to identify patients at risk, such assessment will, at a
      minimum, put into perspective the role that repolarization dynamics may play in
      detecting states of increased arrhythmia risk. Another potential use of these
      techniques is in the assessment of repolarization in patients undergoing EP
      testing, pharmacological therapies or during other provocative testing.

PMID- 14716637
TI  - Respiratory modulation of heart rate and blood pressure during Cheyne-Stokes
      respiration.
AB  - Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with
      oscillations in heart rate (HR) and blood pressure (BP), which have previously
      been attributed to the effects of intermittent hypoxia and arousals from sleep.
      We herein review the major findings from a series of experiments, in which we
      explored the possibility that the ventilatory oscillations of CSR can
      independently modulate HR and BP. Using frequency spectral analysis, we showed
      that CSR in patients with heart failure causes oscillations in HR and BP that are
      eliminated by abolition of ventilatory oscillations, but persist during
      administration of supplemental O2 sufficient to prevent hypoxia. Analysis of the
      effects of arousals showed they have little or no effect on HR or BP independent
      of associated changes in ventilation. Finally, we showed that during simulated
      CSR, healthy awake patients were able to cause HR and BP oscillations in the
      absence of hypoxia or arousals. We conclude that ventilatory oscillations during
      Cheyne-Stokes respiration can modulate HR and BP independent of the effects of
      hypoxia and arousals from sleep.

PMID- 14716638
TI  - Detecting instabilities of cardiac rhythm.
AB  - Diminished beat-to-beat variations in cardiac cycle lengths (CLs) are associated
      with poor prognosis after acute myocardial infarction and in patients with heart
      failure. Short-long-short sequences of cardiac cycles, or ultra-short rhythm
      instabilities, precede initiation of ventricular tachyarrhythmias in some
      patients. However, little is known about clinical or prognostic significance of
      abrupt short-term instabilities in CL (AICL) that occur minutes to hours before
      the event, in part because appropriate analytical methods are lacking. Although
      various techniques have been used to analyze CL changes, methods for analysis of
      AICL are limited. We compared performance of time domain, spectral, nonlinear,
      and pattern recognition techniques with respect to the detection and
      quantification of AICL. Because of high intra- and inter-subject variability of
      CL, pattern recognition techniques compared favorably to other studied methods.
      In continuous ambulatory ECG recordings, AICL occurred hours before spontaneous
      initiation of sustained atrial and ventricular arrhythmias in different patient
      populations. AICL were also found prior to the onset of spontaneous ventricular
      arrhythmias in a mouse model of congestive heart failure. To quantify AICL, we
      used the number of unstable orthogonal projection coefficients; this number
      gradually increased hours before the event. Removal of ectopic beats reduced but
      did not eliminate AICL. To illustrate potential physiological effects and
      temporal evolution of AICL, we used a simple, continuous, two-dimensional model
      of cardiac tissue governed by the Morris-Lecar equations. Computer simulations in
      this model showed that AICL may lead to gradual accumulation of spatial
      irregularities of the propagation wavefront giving rise to the initiation of
      reentry. Time-frequency analysis of the most significant eigenvectors of cardiac
      rhythm in subjects undergoing head-up tilt showed that AICL could indicate
      instabilities and unsuccessful adaptation of autonomic nervous system activity to
      physiological stimuli.

PMID- 14716639
TI  - Analysis of electrocardiograms for subcutaneous monitors.
AB  - We are developing a subcutaneous cardiac arrest monitor and alarm with electrodes
      that have spacing of a few centimeters. We hypothesize that closely spaced
      bipolar electrodes that provide QRS amplitudes of a millivolt or more in sinus
      rhythm (SR) will not provide similar amplitudes during ventricular
      tachyarrhythmia (VT/VF), and that an orthogonal set of electrode pairs in
      diagonal is necessary to produce signals of sufficient amplitude in order to
      distinguish these rhythms. METHODS: Forty patients were studied during ICD
      implantation in the clinical electrophysiology laboratory. A square array of 9
      electrodes with 4- to 10-cm spacing between adjacent electrodes was placed on the
      patient's anterior chest over the left heart. The center electrode in the left
      most column is located in the 5th intercostal space at the left sternal border.
      Eight-channel recordings were made in SR and during induced VT/VF from the 8
      peripheral electrodes referenced to the central member of the array. From these
      recordings all 20 bipolar ECGs of adjacent (including diagonally adjacent)
      electrodes were constructed algebraically. QRS peak-peak amplitudes in SR and
      VT/VF were measured in each bipolar lead and in the spatial vector formed by
      summing the squares of each adjacent and orthogonal pair of these leads. RESULTS:
      Electrode pairs that yielded optimal ECG amplitudes in SR were not always the
      pairs that yielded optimal amplitudes in VT/VF. But in every patient two
      orthogonal pairs could be found whose QRS vector amplitude is sufficient in both
      SR and VT/VF to separate the rhythms. CONCLUSIONS: A patient-defined set of
      bipolar electrode pairs is suitable for automatic separation of SR and VT/VF by
      rate in subcutaneous ambulatory monitoring.

PMID- 14716642
TI  - Total hip arthroplasty in skeletal dysplasias: patient selection, preoperative
      planning, and operative techniques.
AB  - Patients with substantial skeletal dysplasia and hip arthritis are poor
      candidates for noncustom total hip arthroplasty (THA) because of hip size and
      deformity. To determine the efficacy of THA via modified prostheses and surgical
      techniques in this population, the authors analyzed 9 consecutive THAs in 7 small
      stature adults (mean height, 118.6 cm; mean weight, 47.5 kg). The Student t-test
      was used to test for significant (P < 0.05) differences in outcome variables.
      Seven hips received custom femoral components based on imaging studies. Five hips
      required extensive soft-tissue releases secondary to severe contractures. Follow
      up radiographs (range, 24-56 months) showed adequate position of all prostheses
      and no loosening. Follow-up mean pain and function scores (Harris Hip Score and
      WOMAC Arthritis Index) showed significant improvement from preoperative levels.

PMID- 14716643
TI  - Femoral component revision using an extensively hydroxyapatite-coated stem.
AB  - Femoral component revisions with extensively coated stems have shown promising
      clinical results, although concerns over stress shielding still exist. We
      retrospectively reviewed 59 patients undergoing femoral component revision with
      an extensively hydroxyapatite (HA)-coated stem. The average length of follow-up
      was 3.3 years (range, 2-5 years). The average preoperative Harris Hip Score was
      43 points, which improved to 86 points at the latest follow-up (P < .01). The
      overall mechanical failure rate was 2%. No evidence of stress shielding was seen
      in 78% of patients. The clinical results of this series using an extensively HA
      coated stem are similar to those using an extensively porous-coated stem. Long
      term follow-up is required to determine if an extensively HA-coated implant will
      be superior to an extensively porous-coated implant with regard to stress
      shielding.

PMID- 14716644
TI  - Celecoxib versus indomethacin in the prevention of heterotopic ossification after
      total hip arthroplasty.
AB  - A cyclo-oxygenase (COX)-1 and COX-2 inhibitor (indomethacin) and a selective COX
      2 inhibitor (celecoxib) were compared in the prevention of heterotopic
      ossification after total hip arthroplasty. In 250 patients receiving indomethacin
      and in 150 patients receiving celecoxib for 20 days after surgery, an overall
      incidence of heterotopic ossification of 17.5% and 14.3% was seen, respectively
      (difference not statistically significant: P > .05). No grade III or IV
      ossifications were seen in either group. Twenty-one patients in the indomethacin
      group (8.4%) and 3 patients in the celecoxib group (2.0%) required treatment
      discontinuation, because of side effects (P < .05). Celecoxib, a selective COX-2
      inhibitor, shows the same efficacy as indomethacin in the prevention of
      heterotopic ossification after hip prosthesis with significantly fewer side
      effects.

PMID- 14716645
TI  - The correction of severe varus deformity in total knee arthroplasty by tibial
      component downsizing and resection of uncapped proximal medial bone.
AB  - The clinical and radiologic outcome of 10 patients (12 knees) with a mean varus
      deformity of 24 degrees (range, 20 degrees to 40 degrees ) treated with total
      knee arthroplasty (TKA) is presented. We describe a technique of downsizing and
      lateralizing the tibial component with subsequent removal of the proximal medial
      tibia flush with the downsized component. At a mean follow-up of 42 months
      (range, 12 to 64 months), the mean preoperative Knee Society and function scores
      had improved from 24 and 34 to 94 and 85, respectively, at follow-up. No implant
      has been revised. At follow-up evaluation, no evidence of osteolysis or
      radiographic loosening was seen and the mean tibiofemoral angle was 4 degrees of
      valgus. This technique provides mid-term stable correction and excellent clinical
      and radiographic results in patients with severe varus deformity.

PMID- 14716646
TI  - Primary total hip arthroplasty with a flanged, cemented all-polyethylene
      acetabular component: evaluation at a minimum of 20 years.
AB  - One hundred twenty-three consecutive primary total hip arthroplasties in 107
      patients were performed with the insertion of a cemented, all polyethylene,
      flanged acetabular component. At a minimum of 20 years, 66 patients had died (75
      hips) and 8 patients (8 hips) were lost to follow-up evaluation, leaving 40 hips
      in 33 patients. At a mean of 21.1 years, 2 cups had been revised for aseptic
      loosening, one well-fixed cup was revised at the time of femoral component
      revision, and 4 additional cups had definite evidence of radiographic loosening.
      Survivorship analysis revealed a 77.3% survivorship for the component at 21
      years, with revision or definite loosening as an endpoint (95% confidence
      interval, 67.8%-86.8%).

PMID- 14716647
TI  - Experiences with the BiCONTACT revision stems with distal interlocking.
AB  - The first consecutive 68 revision total hip arthroplasties of a cementless distal
      interlocking femoral stem (BiCONTACT; Aesculap AG, Tuttlingen, Germany) are
      included in this study. Average follow-up time was 40 months (range, 36-49
      months). At follow-up evaluation, one patient had died, and one could not be
      located. The average Harris hip score improved from 60 points to 88 points. All
      cases showed radiographic evidence of a bone ingrown prosthesis, and no
      subsidence was seen. No osteolysis and no radiologic loosening were noted. No
      repeat revision was needed during the follow-up period. The results of the distal
      interlocking femoral stems (BiCONTACT) in cementless revision total hip
      arthroplasty were satisfactory. These findings suggest that a diaphyseal fixation
      of the revision femoral stem with distal interlocking screws can provide primary
      axial and rotational stability of the prosthesis in revision surgery.

PMID- 14716648
TI  - Comparison of the PFC Sigma fixed-bearing and rotating-platform total knee
      arthroplasty in the same patient: short-term results.
AB  - This study compares the fixed-bearing PFC Sigma Total Knee Arthroplasty to the
      recently introduced rotating-platform version of the same design in 26 patients.
      At an average follow-up time of 46 months for the fixed-bearing side and 16
      months for the rotating-platform side, no significant differences were found in
      terms of knee preference, knee pain, range of motion, overall satisfaction, or
      Knee Society scores (KSSs). No revisions, subluxations, dislocations, or
      infections were seen. Also no radiographic evidence of component loosening,
      osteolysis, or malalignment was found in any knee. The results of cementing the
      PFC Sigma rotating-platform, posterior-stabilized total knee show excellent
      patient satisfaction at 1 year and comparable clinical and radiographic results
      to the fixed-bearing version.

PMID- 14716649
TI  - Anatomic risk of peroneal nerve injury with the "pie crust" technique for valgus
      release in total knee arthroplasty.
AB  - Peroneal nerve damage can occur during total knee arthroplasty because of
      indirect or direct injury. The potential for direct laceration injury exists when
      performing the "pie crust" lateral soft-tissue release in a valgus knee. To
      assess this risk, the axial, magnetic resonance images of 60 adult knees were
      evaluated. The distance from the peroneal nerve to the tibia was measured at the
      level of the standard tibial resection. At this level, the lateral gastrocnemius
      muscle is interposed between the capsule and the nerve. The mean nerve to bone
      distance was 1.49 cm (0.91-2.18 cm). These results suggest that the peroneal
      nerve is adequately protected at the posterolateral corner of the knee but that
      the "pie crust" release should be performed carefully.

PMID- 14716650
TI  - Transcutaneous electrical nerve stimulation for postoperative pain relief after
      total knee arthroplasty.
AB  - Transcutaneous electrical nerve stimulation (TENS) has been used to treat chronic
      pain syndromes and has been reported to be of some utility in the treatment of
      postsurgical pain. A randomized, blinded, placebo-controlled trial was designed
      to evaluate the utility of TENS after total knee arthroplasty. Patients were
      randomly enrolled into patient-controlled anesthesia (PCA) alone, PCA plus TENS,
      or PCA plus sham TENS. The cumulative dose of morphine by PCA for each group was
      used as the end-point of the study. There was no significant reduction in the
      requirement for patient-controlled analgesia with or without TENS. We conclude
      that there is no utility for TENS in the postoperative management of pain after
      knee arthroplasty.

PMID- 14716651
TI  - Posterior cruciate ligament-substituting total knee arthroplasty in young
      rheumatoid patients with advanced knee involvement.
AB  - The integrity and strength of the posterior cruciate ligament (PCL) in the
      rheumatoid knee are known to be suboptimal. However, the results of PCL
      substituting total knee arthroplasty in rheumatoid patients are not well
      documented. We reviewed 86 PCL-substituting total knee arthroplasties in 52
      rheumatoid patients with grade IV or V radiographic disease. The mean age at
      surgery was 41.9 years. All patients underwent follow-up evaluation for an
      average of 7.8 years. Revision was performed for 1 knee because of aseptic
      loosening of the tibial component, and for 3 knees because of deep infection. An
      isolated insert exchange was performed on one knee. Using revision of any
      component for aseptic loosening or radiographic loosening as the end point, the
      mean 10-year survival rate was 94.0%.

PMID- 14716652
TI  - Total knee arthroplasty in hemophilic arthropathy.
AB  - Total knee arthroplasty (TKA) is very effective in relieving pain and improving
      function in patients with advanced hemophilic arthropathy. Because of intra
      articular fibrosis and extra-articular muscle contracture, the gain in motion
      after TKA has been unsatisfactory. The purpose of this study is to report the
      results of TKA in patients with hemophilia using posterior cruciate ligament
      (PCL)-sacrificing prostheses. From April 1987 to May 1998, 9 patients underwent
      14 PCL-sacrificing TKAs for advanced hemophilic arthropathy. The average length
      of follow-up evaluation in surviving patients (13 knees) was 77 months (range, 25
      159). A statistically significant difference was found between the preoperative
      and postoperative values with respect to pain score (5 vs 48), functional score
      (42 vs 78), flexion deformity (17 degrees vs 5 degrees ), and flexion range (56
      degrees vs 81 degrees ). Nine complications occurred in 6 knees. One patient died
      from HIV-related complications, and none of the patients seroconverted to HIV
      during the follow-up period.

PMID- 14716653
TI  - Efforts to improve cementless femoral stems in THR: 2- to 5-year follow-up of a
      high-offset femoral stem with distal stem modification (Secur-Fit Plus).
AB  - A retrospective review of 81 sequential primary total hip arthroplasties using a
      cementless, high-offset femoral stem was performed. Follow-up was 24 to 60
      months. The average age at the time of surgery was 54 years. The femoral bone
      types were: 36% Dorr A, 51% Dorr B, and 13% Dorr C. The mean postoperative Harris
      Hip Score was 95. The mean postoperative Oxford score was 17. Eighty-five percent
      had no clinical leg-length difference. All stems were radiographically stable.
      The stem features of hydroxyapatite coating on a rough circumferential titanium
      arc-deposit proximal surface in conjunction with distal flutes seem to provide
      immediate stability, making this implant clinically versatile. Potential benefits
      of increased offset include improved joint stability and avoidance of leg
      lengthening.

PMID- 14716654
TI  - Surface analysis of early retrieved acetabular polyethylene liners: a comparison
      of conventional and highly crosslinked polyethylenes.
AB  - In vivo wear behavior of 16 highly cross-linked and 19 conventional polyethylene
      acetabular explants, at an average in vivo duration of 6 months were studied.
      Highly cross-linked groups showed machining marks from the original manufacturing
      process in some areas and extensive scratching and some polishing of the
      articulating surfaces. The conventional group showed greater loss of machining
      marks, scratching, and polishing. Representative samples were melted to allow
      recovery of plastic deformation and to show true removal of material caused by
      wear. Melt-recovery experiments consistently showed the disappearance of surface
      scratches and the restoration of the original machining marks in the highly cross
      linked explants. In the conventional group, few of the scratches were eliminated
      and only limited restoration of the machining marks was apparent. These
      observations support the hypothesis that the early in vivo scratching of highly
      cross-linked polyethylene acetabular liners is primarily caused by plastic
      deformation.

PMID- 14716655
TI  - Role of core biopsy in diagnosing infection before revision hip arthroplasty.
AB  - A prerevision core biopsy from a failed hip joint was performed in 41 hips (38
      patients) with a high index of suspicion for sepsis to determine its efficacy in
      diagnosing sepsis. Seven hips were known septic failures, and core biopsy was
      undertaken to confirm resolution of sepsis. Forty hips were revised, whereas 1
      hip had excision of heterotopic bone. Cultures and permanent histologic sections
      were obtained during subsequent surgeries, and findings were compared with the
      results of core biopsy. The commonest organisms isolated were coagulase-negative
      staphylococci and Propionibacterium acne. In patients without a history of
      sepsis, core biopsy diagnosed infection with sensitivity of 80%, specificity of
      100%, accuracy of 97%, and positive predictive value of 100% using histologic
      evidence of sepsis at revision as the standard. Core biopsy, however, had low
      sensitivity and accuracy in establishing resolution of infection in patients with
      a history of septic failure. Cultures from the aspirate had 44% sensitivity and
      positive predictive value of 57%. Core biopsy is useful for investigating failed
      arthroplasties with suspected sepsis. It has advantages of hip aspiration and
      allows examination of periprosthetic tissue histology. Its role in diagnosing
      resolution of infection in previously septic failures, however, is limited.

PMID- 14716656
TI  - In vivo surface wear mechanisms of femoral components of cemented total hip
      arthroplasties: the influence of wear mechanism on clinical outcome.
AB  - The appearance and mechanism of femoral stem wear was studied in 172 retrieved
      femoral components, of which 74 stems had been stable in vivo. Macroscopic,
      microscopic, and nano-level scales of examination were used. Loss of stem surface
      in response to micromotion (wear) was found to affect 93% of stems. However,
      changes were frequently difficult to see with the naked eye, and in 19% of cases
      they would have been missed completely without the use of light microscopy. The
      surface finish of the prosthesis determined the mechanism of stem wear. Matte
      surfaces showed typical abrasive processes that also damage the cement, releasing
      particulate debris from the cement and metal surfaces. This may destabilize the
      stem within the cement. Polished stems showed a typical fretting appearance with
      retention of debris on the stem surface and without significant damage to the
      cement. These differences in wear mechanism between matte and polished stems have
      significant effects on stem function.

PMID- 14716657
TI  - Effects of calcium ion implantation on osseointegration of surface-blasted
      titanium alloy femoral implants in a canine total hip arthroplasty model.
AB  - Osteoconductivity of titanium-alloy implants may be improved when surface
      modified by calcium ion (Ca2+) implantation. We studied the effects of Ca2+
      implantation on osseointegration of a grit-blasted titanium-alloy stem using a
      canine total hip arthroplasty model. Fifteen dogs underwent bilateral hip
      arthroplasties and were sacrificed at 1, 6, and 12 months postoperatively. The
      hip components were evaluated by radiographic, qualitative, and quantitative
      histology methods. Radiographically and histologically, both Ca(2+)-implanted and
      non-Ca(2+)-implanted stems were well integrated. Ca(2+)-implanted stems had
      greater new bone apposition than non-Ca(2+)-implanted stems, although the
      difference was significant only at 1 month (15.8% +/- 3.5% of the implant
      perimeter for non-Ca(2+)-implanted, 25.4% +/- 4.7% for Ca(2+)-implanted, P< .05).
      This result could be related to chronological decrease of the dissolution rate of
      calcium ions from Ca(2+)-implanted surface. Although further improvement of the
      Ca2+ implantation technique for a sustained osteoconductive effect is necessary,
      Ca2+ implantation may be beneficial for early fixation of titanium-alloy
      implants.

PMID- 14716658
TI  - Underestimation of osteolysis in posterior stabilized total knee arthroplasty.
AB  - Periprosthetic osteolysis in total knee arthroplasty (TKA) has become a
      significant problem. Routine surveillance is warranted to detect problems that
      may not be symptomatic. The goal of these radiographs is to detect arthroplasty
      related bone loss at an early stage to implement strategies to limit its
      extension. The purpose of this study was to show the extent to which condylar
      osteolysis can be underestimated on routine radiographs. Two cadaveric femurs
      were prepared to receive a posterior stabilized (PS) femoral component. A
      simulated osteolytic lesion was created using acetabular reamers. Lesions of 36
      mm not easily discernible on standard anteroposterior and lateral images were
      easily recognized on oblique films. The oblique radiographs described can help
      with the early recognition of retrofemoral osteolysis about a posterior
      stabilized implant.

PMID- 14716659
TI  - Assessment of bone graft substitutes in autopsy implant retrievals of the
      acetabulum in total hip arthroplasty.
AB  - Two autopsy retrievals of acetabular reconstruction with different bone graft
      substitutes were analyzed. One patient underwent surgery with hydroxyapatite (HA)
      granules, and the other with demineralized bone chips. Incorporation occurred
      with the biomaterial bone-graft substitute HA primarily in the superior part of
      the acetabulum, where the HA was in contact with host cortical bone. No bony
      union occurred with the demineralized bone chips because of motion and migration
      of the acetabular cup. No bone incorporation of either bone-graft substitute was
      observed in the medial wall defects in both patients. There were two important
      findings: (1) the 3- to 8-mm depth and 70% to 75% surface of union of the HA bone
      graft substitute to host cortical bone was the same as seen with morselized,
      fresh-frozen bone graft; and (2) union of graft material to host bone was
      dependent on secure fixation of the acetabular construct.

PMID- 14716660
TI  - Embolization of traumatic pseudoaneurysms after total knee arthroplasty.
AB  - We report on 2 cases of traumatic pseudoaneurysm after total knee arthroplasty.
      In one patient, a hemarthrosis and a pulsatile antecubital mass developed 1 month
      after arthroplasty, prompting angiography. In the second patient, evacuation of a
      large hemarthrosis was performed before angiography and embolization. In both
      patients, the pseudoaneurysm was successfully treated without the need for
      surgical repair, using percutaneous thrombin injection or transcatheter
      embolization. No recurrence of hemarthrosis was seen in either patient at up to
      24 months of follow-up evaluation. These cases show the use of angiography in
      reconstructed joints when acute or delayed hemarthrosis occurs, and the role of
      embolization techniques in this setting.

PMID- 14716661
TI  - Malformation of the acetabular fossa as a cause of intrapelvic injury in total
      hip arthroplasty: a report of 2 cases.
AB  - We report 2 cases of bone defects of the acetabulum. The first case was a patient
      who underwent a total hip arthroplasty. An intraoperative bleeding occurred
      because of an injury of an intrapelvic artery. Preoperative radiographs did not
      show this bone defect. A similar abnormality of the acetabulum was found in a
      series of 30 pelves that were dissected for a cadaver study. In this case, the
      bone defect was located in the center of the right acetabulum.

PMID- 14716662
TI  - Letter to the editor.

PMID- 14716664
TI  - Letter to the editor.

PMID- 14716672
TI  - Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4
      promotes endosteal bone formation in mice.
AB  - BACKGROUND: Bone loss in osteoporosis is caused by an imbalance between
      resorption and formation on endosteal surfaces of trabecular and cortical bone.
      We investigated the feasibility of increasing endosteal bone formation in mice by
      ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV
      based retroviral vector to express human bone morphogenetic protein 4 (BMP4).
      METHODS: We assessed two approaches for administering transduced MSCs. beta
      Galactosidase (beta-Gal) transduced C57BL/6J mouse MSCs were injected
      intravenously via tail vein or directly injected into the femoral bone marrow
      cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity
      engraftment was assessed. BMP4- or beta-Gal-transduced cells were injected into
      the femoral bone marrow cavity and effects on bone were evaluated by X-ray,
      peripheral quantitative computed tomography (pQCT), and histology. RESULTS: After
      tail-vein injection less than 20% of recipient mice contained beta-Gal-positive
      donor cells in femur, humerus or vertebra marrow cavities combined, and in these
      mice only 0.02-0.29% of injected cells were present in the bone marrow. In
      contrast, direct intramedullary injection was always successful and an average of
      2% of injected cells were present in the injected femur marrow cavity 24 hours
      after injection. Numbers of donor cells decreased over the next 14 days.
      Intramedullary injection of BMP4-transduced MSCs induced bone formation.
      Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14
      days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. CONCLUSIONS:
      The present findings support the feasibility of using ex vivo MSC-based
      retroviral gene therapy to induce relatively sustained new bone formation, with
      normal histological appearance, at endosteal bone sites.

PMID- 14716673
TI  - Factors influencing immune response after in vivo retrovirus-mediated gene
      transfer to the liver.
AB  - BACKGROUND: Highly efficient retrovirus-mediated gene transfer into hepatocytes
      in vivo triggers an immune response directed against transduced hepatocytes. This
      effect may be due either to spreading of retroviral vectors in the blood stream
      with subsequent infection of antigen presenting cells (APCs) or to cross
      presentation of the transgene product present as a contaminant in the viral
      stock. In order to decrease immune response, we evaluated the effect of
      asanguineous perfusion of the liver as well as purification of the viral stock on
      long-term transduction of hepatocytes using the nls-lacZ marker gene. METHODS:
      Animals were divided in four groups. In group 1, the viral supernatant was
      perfused in the regenerating liver after complete vascular exclusion of the
      organ. In group 2, using the same strategy, animals received retroviral
      supernatant that was passed through a beta-galactosidase affinity column to
      reduce beta-galactosidase contamination. In two control groups (respectively
      groups 3 and 4) the corresponding viral supernatants were delivered via
      peripheral injection. RESULTS: In group 1, 23.1% of animals had no immune
      response 2 months after gene delivery vs. 33.4% in group 2, 4.3% in control group
      3, and 0% in control group 4. Statistical analysis of the results demonstrated
      that only the difference between groups 2 and 3 was statistically significant.
      This indicated that both asanguineous perfusion together with passage through an
      affinity column were required to decrease significantly immune response.
      CONCLUSIONS: Our present results suggest that both supernatant contamination and
      viral spreading contribute to immune response after retrovirus-mediated gene
      delivery to the liver.

PMID- 14716674
TI  - In vivo expansion of gene-modified hematopoietic cells by a novel selective
      amplifier gene utilizing the erythropoietin receptor as a molecular switch.
AB  - BACKGROUND: In vivo expansion of gene-modified cells would be a promising
      approach in the field of hematopoietic stem cell gene therapy. To this end, we
      previously developed a selective amplifier gene (SAG), a chimeric gene encoding
      the granulocyte colony-stimulating factor (G-CSF) receptor (GCR), as a growth
      signal generator and the hormone-binding domain of the steroid receptor as a
      molecular switch. We have already reported that hematopoietic cells retrovirally
      transduced with the SAG can be expanded in a steroid-dependent manner in vitro
      and in vivo in mice and nonhuman primates. In this study, we have developed a new
      generation SAG, in which the erythropoietin (EPO) receptor (EPOR) is utilized
      instead of the steroid receptor as a molecular switch. METHODS: Two EPO-driven
      SAGs were constructed, EPORGCR and EPORMpl, containing the GCR and c-Mpl as a
      signal generator, respectively. First, to compare the steroid-driven and EPO
      driven SAGs, Ba/F3 cells were transduced with these SAGs. Next, to examine
      whether GCR or c-Mpl is the more suitable signal generator of the EPO-driven SAG,
      human cord blood CD34(+) cells were transduced with the two EPO-driven SAGs
      (EPORMpl and EPORGCR). Finally, we examined the in vivo efficacy of EPORMpl in
      mice. Irradiated mice were transplanted with EPORMpl-transduced bone marrow cells
      followed by administration of EPO. RESULTS: The EPO-driven SAGs were shown to
      induce more rapid and potent proliferation of Ba/F3 cells than the steroid-driven
      SAGs. The EPORMpl induced more efficient EPO-dependent proliferation of the human
      cord blood CD34(+) cells than the EPORGCR in terms of total CD34(+) cell, c
      Kit(+) cell, and clonogenic progenitor cell (CFU-C) numbers. In the transplanted
      mice the transduced peripheral blood cells significantly increased in response to
      EPO. CONCLUSIONS: The new-generation SAGs, especially EPORMpl, are able to
      efficiently confer an EPO-dependent growth advantage on transduced hematopoietic
      cells in vitro and in vivo in mice.

PMID- 14716675
TI  - Gene transfer and genetic modification of embryonic stem cells by Cre- and Cre-PR
      expressing MESV-based retroviral vectors.
AB  - BACKGROUND: Genetic modification of embryonic stem (ES) cells represents a
      powerful tool for transgenic and developmental experiments. We report that
      retroviral constructs based on murine embryonal stem cell virus (MESV) can
      efficiently deliver and express Cre recombinase or a post-translationally
      inducible Cre-Progesterone receptor (Cre.PR) fusion in mouse fibroblasts and ES
      cells. METHODS: To study the vectors a sensitive reporter cell line, 3TZ, was
      derived from the murine 3T6 fibroblast line that expresses beta-galactosidase
      only upon Cre-mediated recombination. This was used together with the ROSA26-R ES
      cell Cre-reporter system or unmodified mouse ES cells as targets of infection.
      Efficiency of gene transfer was evaluated immunohistochemically by the use of an
      anti-Cre polyclonal antibody, and by monitoring the expression of beta
      galactosidase. RESULTS: Infection of the 3TZ cells with high titer 718C or 719CP
      virus revealed efficient gene transduction of constitutive or hormone-inducible
      recombinase activity, respectively. The vectors efficiently transduced murine ES
      cells with Cre, Cre-PR (fusion of Cre and progesterone receptor) or beta
      galactosidase. Cre-mediated recombination in more than 60% of ROSA26-R ES cells
      was achieved when infected by a VSV-G-pseudotyped MESV retrovirus at MOI of 50.
      CONCLUSIONS: The MESV-based retroviral systems, when combined with hormone
      inducible Cre, represent efficient tools for the transfer of Cre activity in ES
      cells.

PMID- 14716676
TI  - Gene-directed enzyme prodrug therapy for prostate cancer in a mouse model that
      imitates the development of human disease.
AB  - BACKGROUND: Gene-directed enzyme prodrug therapy (GDEPT) based on the E. coli
      enzyme purine nucleoside phosphorylase (PNP) represents a new approach for
      treating slow growing tumours like prostate cancer (PCa). Expressed enzyme
      converts a systemically administered prodrug, fludarabine phosphate, to a toxic
      metabolite, 2-fluoroadenine. Infected and neighbouring cells are killed by a
      bystander effect that results from the inhibition of DNA and RNA synthesis.
      METHODS: These studies were carried out using the transgenic adenocarcinoma of
      the prostate (TRAMP) model that mimics human PCa development and progression.
      Control TRAMP mice were injected intraprostatically with vector vehicle and
      thereafter intraperitoneally with saline or fludarabine phosphate ( approximately
      600 mg/m(2)/day) once daily for 5 consecutive days. Treated mice received a
      single intraprostatic injection containing 10(10) particles of OAdV220, an ovine
      atadenovirus which expresses the E. coli PNP gene under the control of the Rous
      sarcoma virus promoter, followed by systemic fludarabine treatment. The weight of
      the genitourinary tract, seminal vesicles and the prostate as well as animal
      survival were monitored. Tumours were also analysed histologically. RESULTS:
      Preliminary studies showed that fludarabine alone caused no significant change in
      genitourinary (GU) tract weight in TRAMP mice. Animals injected with vector and
      prodrug showed a significant reduction (36-47%) in GU tract weight (ANOVA p =
      0.0002) and a 35-50% reduction in seminal vesicle weight (ANOVA p = 0.0007). In
      particular, the target organ showed a significant 57% reduction in prostate
      weight (ANOVA p = 0.0007). PNP-GDEPT mice also showed a survival advantage over
      control mice. Histological analysis suggested that the cancer progression was
      slowed in GDEPT-treated animals. CONCLUSION: A single course of GDEPT based on
      OAdV-delivered PNP and fludarabine produced highly significant suppression of PCa
      progression in immune-competent TRAMP mice.

PMID- 14716677
TI  - Developing a convenient large animal model for gene transfer to salivary glands
      in vivo.
AB  - BACKGROUND: Localized gene transfer to salivary glands has great potential for
      the treatment of salivary gland, systemic, and oral diseases. The minipig parotid
      gland, given its volume and morphological similarities to the human parotid
      gland, may be useful as a large animal model for pre-clinical gene transfer
      experiments. The purpose of this study was to perform an initial assessment of
      the efficacy and safety of adenoviral-vector-mediated gene transfer to parotid
      glands of miniature pigs. METHODS: AdCMVluc, a recombinant type 5 adenoviral
      (rAd5) vector containing a luciferase reporter gene, was administered to
      miniature pig parotid glands by intraductal cannulation. Five regions of gland
      tissue were obtained to measure the distribution of luciferase activity. The
      effects of time, viral dose, infusate buffer volume, and gland anatomical region
      on transgene expression were determined. Detailed serum chemistry and
      hematological analyses were performed. In addition, AdCMVlacZ, a similar rAd5
      vector encoding beta-galactosidase, was also delivered to determine the parotid
      gland cell types transduced. RESULTS: Luciferase assays indicated that gene
      transfer to miniature pig salivary glands could be readily accomplished using
      rAd5 vectors. Highest transgene expression was found in the center of glands,
      which was > posterior > inferior > anterior > superior tissue regions. Expression
      was maximal on day 2 and declined to background by day 14, and observed in both
      acinar and ductal cells. Several serum chemistry and hematology parameters were
      transiently changed following rAd5 administration. CONCLUSIONS: Transgene
      expression by, and inflammatory response to, rAd5 vectors in minipig parotid
      glands are similar to results seen earlier in rodent studies. This suggests that
      results of salivary gland gene transfer from rodent studies can be extended to a
      larger animal model, and supports the value of using minipigs for pre-clinical
      applications of gene transfer to these tissues. Published in 2004 by John Wiley &
      Sons, Ltd.

PMID- 14716678
TI  - Steric stabilization of poly(2-(dimethylamino)ethyl methacrylate)-based
      polyplexes mediates prolonged circulation and tumor targeting in mice.
AB  - BACKGROUND: Efficient tumor targeting of polymeric gene transfer systems
      (polyplexes) represents a major challenge. To establish tumor targeting after
      intravenous (IV) administration, the circulation lifetime of these systems should
      be sufficiently long. Since naked polyplexes are rapidly eliminated from the
      circulation after IV adminstration, strategies have to be developed to improve
      their pharmacokinetics. METHODS: Complexes of plasmid DNA and poly(2
      (dimethylamino)ethyl methacrylate) (pDMAEMA)-graft-PEG or AB di-block copolymers
      of pDMAEMA and PEG, as well as PEGylated complexes prepared via PEGylation of
      preformed complexes (postPEGylation), were evaluated for their physicochemical
      properties (size and charge) their interactions with blood constituents and
      transfection activity in vitro. The pharmacokinetics and biodistribution of PEG
      polyplexes were studied in mice after IV administration. The degree of
      accumulation in two subcutaneous (SC) mouse tumors after IV administration was
      evaluated for the system with the longest circulation time. RESULTS: It is shown
      that the surface charge of the pDMAEMA-polyplexes was effectively shielded by two
      PEGylation methods (i.e. the use of pDMAEMA-graft-PEG polymers and
      postPEGylation). The shielding effect was the highest for the postPEGylation
      method with PEG(20000), yielding polyplexes that hardly show interactions with
      blood components (i.e. albumin and erythrocytes) and show substantially prolonged
      circulation time in mice after IV administration. The superior colloidal
      stability and circulation kinetics of the postPEGylated polyplexes translated
      into tumor accumulation which amounted to about 3.5% of the injected dose per
      gram tumor tissue in a SC Neuro2A tumor model and to about 4.2% of the injected
      dose per gram tumor tissue in a SC C26 tumor model. CONCLUSIONS: This study shows
      that postPEGylation of pDMAEMA-based polyplexes is the most attractive method to
      prepare polyplexes with long circulating properties. Tumor targeting capacity
      after intravenous administration was demonstrated in two subcutaneous tumor
      models.

PMID- 14716679
TI  - In situ single cell observation by fluorescence resonance energy transfer reveals
      fast intra-cytoplasmic delivery and easy release of plasmid DNA complexed with
      linear polyethylenimine.
AB  - BACKGROUND: The investigation into the intracellular mechanisms for gene
      expression has acquired great impetus for the improvement of the transfection
      efficiency by a non-viral gene delivery system. METHODS: Intracellular
      trafficking as well as release of plasmid DNA (pDNA) complexed with polycations,
      including linear and branched polyethylenimine (LPEI, BPEI) and poly(L-lysine)
      (PLL), were explored under confocal microscopy using fluorescence resonance
      energy transfer (FRET) between a pair of donor-acceptor fluorescent dyes
      (fluorescein and Cy3) tagged on a single pDNA molecule. RESULTS: pDNA complexed
      with LPEI underwent a rapid escape from the endosomes, spreading uniformly into
      the cytoplasm with a substantial decrease in FRET efficiency due to the
      disintegration of LPEI/pDNA polyplex structure. pDNA complexed with BPEI also
      achieved a rapid escape from the endosomes. Nevertheless, the pDNA retained high
      FRET efficiency even after 24 h, indicating an appreciable stability of the
      BPEI/pDNA polyplex to keep pDNA in a condensed state. In the PLL/pDNA polyplexes,
      neither endosome escape nor pDNA decondensation was observed. These intracellular
      characteristics of polyplexes showed a clear correlation to their gene
      transfection efficiency: The LPEI/pDNA revealed a considerably higher and faster
      gene expression compared with BPEI/pDNA. Atomic force microscopy revealed that
      BPEI induced more effective condensation of pDNA than LPEI, being consistent with
      restricted cytoplasmic release of complexed pDNA. CONCLUSION: Fast endosomal
      escape and subsequent smooth disintegration of LPEI/pDNA in the cytoplasm are
      likely to be determining factors for the excellent transfection efficiency of
      this polyplex system. These properties may be particularly beneficial to achieve
      appreciably high gene expression in a prompt manner.

PMID- 14716680
TI  - Partial correction of the alpha-galactosidase A deficiency and reduction of
      glycolipid storage in Fabry mice using synthetic vectors.
AB  - BACKGROUND: Fabry disease is a recessive, X-linked disorder caused by a
      deficiency of the lysosomal enzyme alpha-galactosidase A, leading to an
      accumulation of the glycosphingolipid globotriaosylceramide (GL-3) in most
      tissues of the body. The goal of this study was to determine if systemic delivery
      of a nonviral vector could correct the enzyme deficiency and reduce the levels of
      GL-3 in different tissues of a transgenic knockout mouse model of the disease.
      METHODS: Cationic lipid was complexed with a CpG-depleted plasmid DNA vector and
      then injected intravenously into Fabry mice. The levels of alpha-galactosidase A
      and GL-3 in different tissues were assayed at various time points after
      injection. RESULTS: Expression of alpha-galactosidase A was detected in the
      different tissues of Fabry mice for up to 3 months after complex administration,
      but resulted in minimal reductions in GL-3 levels. However, the use of the anti
      inflammatory drug dexamethasone and multiple dosing increased alpha-galactosidase
      A expression and resulted in significant reductions of GL-3 in all the organs
      with the exception of the kidney. In addition, injecting complex into young Fabry
      mice partially prevented the normal accumulation of GL-3 in the heart, lung, and
      liver. CONCLUSIONS: Systemic delivery of a cationic lipid-pDNA complex partially
      corrected the enzyme deficiency and reduced glycolipid storage in a mouse model
      of Fabry disease. The results are one of the few demonstrations of long-term
      efficacy in a genetic disease model using nonviral vectors. However, substantial
      improvements in expression, especially in critical organs such as the kidney, are
      required before these vectors can become a viable approach to treat Fabry disease
      and other lysosomal storage disorders.

PMID- 14716681
TI  - Local RAD50 gene delivery induces regression of preformed porcine coronary in
      stent neointimal hyperplasia.
AB  - BACKGROUND: Recently, we observed that overexpression of human RAD50 (hRAD50)
      induced p21-dependent cytotoxicity in various cultured cells, and rat and mouse
      tumor models. This study investigated the characteristics of endothelial cell
      (EC) death by hRAD50 and the potential utility of hRAD50 in the development of
      gene therapies for vascular restenosis. METHODS: We studied the effects of
      transient hRAD50 gene transfer using nonliposomal lipid on the survival of
      primary cultured human coronary arterial EC and smooth muscle cells (SMC). Palmaz
      Schatz stents were deployed in two epicardial coronary arteries in each pig (n =
      10). Two weeks later, the patency of the stented arteries was documented by
      coronary angiography, and the hRAD50 construct or empty vector mixed with lipid
      was delivered to one of the stented arteries in each pig using a Dispatch
      catheter. Coronary angiography was repeated 2 weeks after gene delivery and
      histological examination was performed. RESULTS: Lipid-mediated hRAD50 gene
      transfer resulted in the death of EC and SMC. It also increased endothelial
      nitric oxide synthase (eNOS) expression and nitrite production as well as p21
      expression. Pretreatment with NOS and pan-caspase inhibitors completely prevented
      EC death by hRAD50. In the hRAD50-delivered arteries, the percentage of diameter
      stenosis, neointimal area, and pathologic area of stenosis were significantly
      smaller than in the control arteries. eNOS expression increased in the hRAD50
      delivered arteries. Systemic hematologic and chemical values were not affected by
      gene delivery. CONCLUSIONS: Significant regression of preformed in-stent
      neointimal hyperplasia was induced by local hRAD50 gene delivery to stented
      porcine coronary arteries without apparent systemic toxicity.

PMID- 14716682
TI  - Sequence-specific gene silencing in murine muscle induced by electroporation
      mediated transfer of short interfering RNA.
AB  - BACKGROUND: Post-genomic biomedical research requires efficient techniques for
      functional analyses of poorly characterized genes in living organisms. Sequence
      specific gene silencing in mammalian organs may provide valuable information on
      the physiological and pathological roles of predicted genes in mammalian systems.
      Here, we attempted targeted gene knockdown in vivo in murine skeletal muscle
      through the electroporation-mediated transfer of short interfering RNA (siRNA).
      METHODS: siRNA duplexes corresponding to the firefly luciferase (Luc), green
      fluorescent protein (GFP), or glyceraldehyde-3-phosphate dehydrogenase (GAPD)
      genes were delivered by electroporation into the tibial muscle of normal or
      enhanced GFP (EGFP) transgenic mice. Plasmid vectors carrying the Luc, hRluc or
      beta-galactosidase (beta-gal) reporter genes were also delivered. The Luc and
      hRluc activities in the muscle lysates were assayed. The EGFP and GAPD expression
      was detected by fluorescence microscopic observation and RT-PCR, respectively.
      RESULTS: When Luc-specific siRNA was co-delivered with the Luc expression vector
      into the tibial muscle, the reporter gene expression was markedly suppressed
      (less than 1% of the control level) for 5 days. As little as 0.05 micro g of
      siRNA almost completely blocked the reporter gene expression from 10 micro g of
      the plasmid. To examine whether siRNA can also suppress expression of an
      endogenous gene, transgenic mice carrying the EGFP gene received intramuscular
      transfection of a mixture of beta-gal plasmid and GFP-specific siRNA. beta-Gal
      positive cells failed to express detectable levels of EGFP, while EGFP expression
      was not inhibited in control mice that received nonspecific siRNA. Expression of
      GAPD was also suppressed by the specific siRNA. CONCLUSIONS: The present system
      may provide a useful means of phenotypic analysis of genetic information in
      mammalian organs for basic research as well as therapeutic molecular targeting in
      the post-genomic era.

PMID- 14716683
TI  - Intramuscular SP1017-formulated DNA electrotransfer enhances transgene expression
      and distributes hHGF to different rat tissues.
AB  - BACKGROUND: The systemic administration of a therapeutic protein is a common
      approach for the treatment of multiple disorders. Intramuscular (i.m.) injection
      of plasmids, followed by electroporation, has been shown to facilitate naked DNA
      gene transfer in skeletal muscle allowing proteins to be produced and secreted at
      therapeutically relevant levels. METHODS: Plasmid DNA, unformulated or formulated
      with the non-ionic carrier SP1017, was injected at the rat tibialis anterior
      muscle followed by the application of electric pulses. Follow-up of protein
      expression was measured. RESULTS: In our study we report that the non-ionic
      carrier SP1017 significantly increases transgene expression in rat muscle after
      the i.m. injection of a formulated-pCMVbeta plasmid followed by electroporation.
      Such increased expression was observed after delivering square-wave unipolar
      electric pulses at two different field strengths: low (110 V/cm) and high (175
      V/cm). Moreover, elevated secreted placental alkaline phosphatase (SEAP) plasma
      levels were achieved with low-voltage (110 V/cm) electroporation. Our results
      also show that human hepatocyte growth factor (hHGF) can be produced from rat
      muscle and delivered to blood circulation at a biologically active level after a
      single i.m. injection of an SP1017-formulated plasmid (pCMV/hHGF) followed by
      electroporation. Tissue distribution studies mostly identified hHGF in the liver,
      but it was also found in the kidneys and lungs suggesting that here too the HGF
      could be of therapeutic benefit. CONCLUSIONS: Our results indicate that SP1017
      enhances the expression of electrotransferred genes. Such a delivery approach
      could prove an efficient method for the systemic production of therapeutic
      proteins.

PMID- 14716684
TI  - Use of the norepinephrine transporter as a reporter gene for non-invasive imaging
      of genetically modified cells.
AB  - BACKGROUND: The norepinephrine transporter (NET) is a high-affinity transporter
      for catecholamines. Its expression is almost exclusively restricted to the
      sympathetic nervous system. In this study we evaluated whether the NET can be
      used as a reporter gene for non-invasive imaging of genetically modified cells
      with radiolabeled probes. METHODS: Human A431, HT1080 and murine CMS-5 cells were
      retrovirally transduced with bovine NET cDNA. Transduced and parental cells were
      incubated in vitro with [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG). The
      specificity of tracer uptake was determined by adding the NET inhibitor
      imipramine. Rat PC12 cells served as positive controls. Parental and A431NET
      cells were xenotransplanted into nude mice and tumor uptake of [(123)I]MIBG in
      vivo was determined after tracer administration. RESULTS: In vitro stably
      transduced cells showed a 66- to 120-fold higher [(131)I]MIBG uptake than
      parental cells. Incubation with imipramine reduced [(131)I]MIBG uptake of
      transduced cells to the level found in parental cells. More than 70% of the
      initial radioactivity was retained in all transduced cell lines after 2 h
      incubation with tracer-free medium. [(131)I]MIBG uptake in PC12 cells, which
      express the NET endogenously, was 20- to 28-fold lower than in transduced cells.
      In vivo, A431NET tumors demonstrated a 33-fold higher [(123)I]MIBG uptake than
      parental tumors. Gamma camera images 24 h after tracer injection showed no tracer
      uptake in parental A431 tumors, but clear images of A431NET tumors. CONCLUSIONS:
      Transduction of tumor cells with NET cDNA causes highly specific uptake and
      significant retention of catecholamine analogs in vitro and in vivo. These
      characteristics make the NET suitable as a reporter gene for non-invasive
      monitoring of gene transfer.

PMID- 14716685
TI  - Insertional mutagenesis and oncogenesis: update from non-clinical and clinical
      studies. Gene Therapy Expert Group of the Committee for Proprietary Medical
      Products (CPMP), European Agency for the Evaluation of Medical Products - June
      2003 meeting.

PMID- 14716687
TI  - From restriction factors to restriction enzymes.

PMID- 14716688
TI  - Hepatitis B virus genotypes: comparison of genotyping methods.
AB  - There are eight genotypes of HBV designated A to H based on greater than 8%
      nucleotide variation over the entire genome. Hepadnaviruses infecting primates
      like the chimpanzee, orangutan and gibbon are very similar and can be regarded as
      genotypes of HBV. The eight genotypes of HBV show a distinct geographical
      distribution and influence the course of disease and the prognosis of treatment.
      Due to the variability of HBV, diagnostic procedures risk giving false-negative
      results or reporting an inaccurately low quantitative result. Thus, the
      variability of HBV genotypes can influence the interpretation of diagnostic data
      and the therapeutic decisions thereof in an unwanted way. HBV genotypes differ in
      the length of their genomes. The old system of numbering HBV nucleotides from the
      start of a non-conserved EcoRI site in the genome leads to difficulties in
      comparing nucleotide positions between genotypes. A numbering system is presented
      which avoids this problem. In addition we discuss the currently available methods
      for genotyping HBV.

PMID- 14716689
TI  - Rhinovirus and the lower respiratory tract.
AB  - Human rhinoviruses (HRVs) are well-recognised causes of common colds and
      associated upper respiratory tract complications such as sinusitis and otitis
      media. This article reviews information linking HRV infection to illness in the
      lower respiratory tract. HRVs are capable of efficient replication in vitro at
      temperatures present in the tracheobronchial tree and have been shown to cause
      productive infection, elaboration of cytokines and chemokines, and up-regulation
      of cell surface markers in human bronchial epithelial cells. In situ
      hybridisation studies have proven that HRV infection occurs in the
      tracheobronchial tree following experimental infection. Clinical studies report
      that HRV infection is the second most frequently recognised agent associated with
      pneumonia and bronchiolitis in infants and young children and commonly causes
      exacerbations of pre-existing airways disease in those with asthma, chronic
      obstructive pulmonary disease or cystic fibrosis. HRV infection is associated
      with one-third to one-half of asthma exacerbations depending on age and is linked
      to asthma hospitalisations in both adults and children. Limited information
      implicates HRV infection as a cause of severe lower respiratory tract illness in
      older adults and in highly immunocompromised hosts, particularly bone marrow
      transplant recipients. More information is needed about the pathogenesis of HRV
      infection with regard to lower respiratory tract complications in these diverse
      patient groups. Given the large unmet medical need associated with HRV
      infections, safe and effective antiviral agents are needed for both prevention
      and treatment of these infections.

PMID- 14716690
TI  - Herpes simplex virus gene products: the accessories reflect her lifestyle well.
AB  - Herpes simplex virus (HSV) genomic DNA contains at least 74 distinct genes. A set
      of 40 genes, termed the 'core genes', is commonly found in all herpesviruses;
      their products include four capsid proteins, six DNA replication proteins, seven
      DNA packaging/cleavage proteins, four envelope glycoproteins, as well as several
      others. Although approximately half of the HSV genes are not essential for
      replication in cell cultures, all accessory gene products are predicted to play
      indispensable roles for viral replication and dissemination in vivo. Intensive
      studies have been undertaken to elucidate the functions and roles of HSV gene
      products, and we are now able to address, at least partially, the biological
      aspects of all HSV encoded proteins. This article is a brief summary of our
      present knowledge of the functions and roles of HSV gene products with special
      attention focused on UL14, UL34, UL51, UL56 and US3, all of which are thought to
      be involved in HSV egress. Furthermore, efforts are discussed to generate
      replication-competent HSV lacking a single or multiple accessory gene(s) for
      potential use in gene therapy or as anti-cancer therapeutics. Finally, specific
      HSV gene products are being explored as therapeutic agents.

PMID- 14716691
TI  - Prospects for antiviral ribozymes and deoxyribozymes.
AB  - Ribozymes and deoxyribozymes (collectively referred to as nucleic acid enzymes)
      can be designed to cleave substrate mRNAs in a sequence-specific manner, and thus
      represent a potentially important tool to inhibit selectively the expression of
      deleterious genes. Nucleic acid enzymes can be delivered to cells either as genes
      encoding RNA enzymes (ribozymes), or exogenously as in vitro produced agents.
      This review focuses in particular on the 'exogenous application' of ribozymes and
      deoxyribozymes as antiviral drugs. In the past few years, the therapeutic
      development of ribozymes and deoxyribozymes has encountered a variety of
      problems, several of which have now been solved thanks to a massive amount of
      research. Much progress has been made towards understanding the structure and
      mechanism of these catalysts, improving their stability and effectiveness in
      vivo, and investigating their clinical usage. Despite this, it is not yet clear
      whether these molecules can be developed into clinically useful pharmaceutical
      preparations. To address the long-term prospects of this class of therapeutics,
      it is necessary to consider their intrinsic capabilities and limits, the
      developmental difficulties that they still face and the comparative advantages
      and disadvantages they may offer with respect to other oligonucleotide-based
      therapeutic approaches.

PMID- 14716693
TI  - Randomized placebo-controlled trial of donepezil in cognitive impairment in
      Parkinson's disease.
AB  - OBJECTIVE: To evaluate the efficacy and safety of donepezil, an
      acetylcholinesterase inhibitor, as a treatment for cognitive impairment and
      dementia in patients with Parkinson' s disease (PD). METHODS: Using a randomized,
      double-blind, placebo-controlled design, nine patients received placebo and seven
      patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2
      (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological
      battery that assessed global cognitive status as well as memory, attention,
      psychomotor speed, and visuospatial and executive functions. Secondary efficacy
      outcomes were psychiatric symptom and activities of daily living ratings. Primary
      safety measures were motor signs and assessments of adverse effects. RESULTS:
      Patients on donepezil showed selective and significant (p<0.05) improvement on
      the memory subscale of the Dementia Rating Scale. There was also a trend toward
      improvement on a measure of psychomotor speed and attention. There were no group
      differences in psychiatric status, motor function, or activities of daily living
      as measured at baseline or end-point. Adverse effects resulted in premature
      withdrawal of four patients on donepezil, two for peripheral cholinergic effects
      and one for increased parkinsonism. Side effects were associated with dosage
      increases. CONCLUSION: Donepezil has a beneficial effect on memory and may
      improve other cognitive deficits in patients with PD and cognitive impairment.
      However, variable tolerability in our sample underscores the need for careful
      monitoring when prescribing donepezil to patients with PD, especially with dosage
      increases.

PMID- 14716694
TI  - A randomized, placebo-controlled study of the efficacy and safety of sertraline
      in the treatment of the behavioral manifestations of Alzheimer's disease in
      outpatients treated with donepezil.
AB  - OBJECTIVE: To examine the safety and efficacy of sertraline augmentation therapy
      in the treatment of behavioral manifestations of Alzheimer's disease (AD) in
      outpatients treated with donepezil. METHODS AND MATERIALS: Patients with probable
      or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a
      severity score > or =2 in at least one domain), were treated with donepezil (5-10
      mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation
      therapy with either sertraline (50-200 mg) or placebo. Primary efficacy measures
      were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global
      Impression Improvement (CGI-I) and Severity (CGI-S) scales. RESULTS: 24 patients
      were treated with donepezil+sertraline and 120 patients with donepezil+placebo.
      There were no statistically significant differences at endpoint on any of the
      three primary efficacy measures. However, a linear mixed model analysis found
      modest but statistically significantly greater improvements in the CGI-I score on
      donepezil+sertraline. Moreover, in a sub-group of patients with moderate-to
      severe behavioral and psychological symptoms of dementia, 60% of patients on
      sertraline vs 40% on placebo (p = 0.006) achieved a response (defined as > or =
      50% reduction in a four-item NPI-behavioral subscale). One adverse event
      (diarrhea) was significantly (p < 0.05) more common in the donepezil+sertraline
      group compared to the donepezil+placebo group. CONCLUSION: Sertraline
      augmentation was well-tolerated in this sample of AD outpatients. In addition,
      post hoc analyses demonstrated a modest but statistically significant advantage
      of sertraline over placebo augmentation in mixed model analyses and a clinically
      and statistically significant advantage in a subgroup of patients with moderate
      to-severe behavioral and psychological symptoms of dementia.

PMID- 14716695
TI  - The persistence of neuropsychiatric symptoms in dementia: the Cache County Study.
AB  - OBJECTIVE: To estimate the 18-month persistence of neuropsychiatric symptoms in
      dementia in a population-based sample, and to compare the severity of
      neuropsychiatric symptoms at baseline to the severity at 18-month follow-up.
      METHODS: A population-based sample of 329 residents of Cache County, Utah,
      diagnosed with dementia was rated on the Neuropsychiatric Inventory (NPI). Of the
      204 participants with neuropsychiatric symptoms at baseline (defined as total NPI
      score >0), NPI data were obtained approximately 18 months later on 117 who were
      alive and available for follow-up. RESULTS: Eighty-one percent of those with
      neuropsychiatric symptoms at baseline (defined as total NPI score>0) continued to
      have at least one symptom at follow-up. Sixty-seven percent of participants with
      a clinically significant total NPI score (defined as > or = 4) at baseline
      continued to have a clinically significant total NPI score at follow-up. Among
      the ten neuropsychiatric domains assessed at baseline, delusions persisted in
      65.5% of individuals, followed by depression (58.3%), and aberrant motor behavior
      (55.6%), while hallucinations and disinhibition persisted in only 25.0% and 11.1%
      respectively. In participants who were symptomatic at both baseline and follow
      up, the mean severity scores at the two observation points were comparable in all
      ten neuropsychiatric domains. CONCLUSIONS: Neuropsychiatric symptoms in dementia
      overall were highly persistent. Among those in whom symptoms did persist, symptom
      severity a year and a half later appeared to be comparable.

PMID- 14716696
TI  - Poor mental and physical health differentially contributes to disability in
      hospitalized geriatric patients of different ages.
AB  - OBJECTIVE: To evaluate the relationship between depressive symptoms, cognition
      and somatic diseases on functional status of geriatric patients at hospital
      discharge. METHOD: Patients 65+ years consecutively admitted to the acute care
      geriatric ward of the Internal Medicine Department I, Civil Hospital of Brescia,
      Italy, from February 1998 to December 2000 (n = 830) were examined. Functional
      disability was defined as need of physical assistance in at least one of the
      basic Activities of Daily Living (ADL). The Greenfield Index of Disease Severity
      (IDS) and the Geriatric Index of Comorbidity (GIC) were used to measure number
      and severity of diseases. The Mini-Mental State Examination (MMSE) assessed
      cognitive status and the Geriatric Depression Scale (GDS) measured depressive
      symptoms. RESULTS: Prevalence of functional disability at discharge was 29.3% in
      the younger age group (65-74 years) and 55.2% in the older age group (75+ years).
      Using logistic regression models, older age, poorer cognitive status, and
      depressive symptoms were independently associated with functional disability in
      the younger and older age group, respectively. Additionally cognitive impairment
      and depressive symptoms showed an additive association with disability,
      especially in younger patients, while comorbidity was correlated with functional
      status only in the oldest old, in particular among those who were cognitively
      impaired. CONCLUSION: Functional disability after acute hospitalization is highly
      prevalent in geriatric patients. Depressive symptoms, comorbidity, and cognitive
      impairment often coexist, interact and are differentially associated with
      function depending on age. Considering that depressive symptoms are a modifiable
      problem, their detection in hospital settings may help clinicians in targeting
      subjects at high risk of functional disability.

PMID- 14716697
TI  - Elderly suicide attempters with depression are often diagnosed only after the
      attempt.
AB  - OBJECTIVE: No previous study has comprehensively investigated the pattern of
      health care contacts among elderly subjects attempting suicide. The present study
      compared elderly suicide attempters with younger attempters, before and after
      attempted suicide, in terms of health care contacts, clinical diagnoses of mental
      disorders, and characteristics predicting lack of treatment contact after the
      index attempt. METHODS: All consecutive 1198 suicide attempters treated in
      hospital emergency rooms in Helsinki, Finland, from 15.1.1997 to 14.1.1998 were
      identified and divided into two age groups: (1) elderly suicide attempters aged
      60 years or more (n = 81) and (2) suicide attempters aged under 60 years (n =
      1117). RESULTS: During the final 12 months before the attempt, the majority of
      elderly suicide attempters had a contact with primary health care, but their mood
      disorders were likely to have remained undiagnosed before the index attempt. In
      primary health care, only 4% had been diagnosed with a mood disorder before the
      attempt, but 57% after (p < 0.001). After the suicide attempt, most elderly
      suicide attempters were referred for aftercare, two thirds having contact with
      psychiatric care. CONCLUSIONS: For purposes of preventing suicidal behaviour,
      screening for depression, plus further education on recognition, diagnosis and
      treatment of mood disorders among the elderly in primary health care setting are
      needed.

PMID- 14716698
TI  - Cross-national comparison and validation of the Alzheimer's Disease Assessment
      Scale: results from the European Harmonization Project for Instruments in
      Dementia (EURO-HARPID).
AB  - BACKGROUND: The Alzheimer's Disease Assessment Scale (ADAS) is often used in
      international multicenter trials. Use across countries presupposes correct
      translation and adaptation of the scale, and maintenance of its psychometric
      properties. OBJECTIVES: To compare the various translations of the ADAS used in
      Western Europe, to design internationally harmonized translations and to validate
      these. SETTING: International cooperative study in eight European countries.
      METHODS: An inventory was made of existing versions of the ADAS-Cog used in eight
      European countries, and adaptations were made. The concurrent validity of the
      harmonized versions of the ADAS was tested in 283 patients with probable or
      possible Alzheimer's disease. The Nurses Observation Scale for Geriatrics
      (NOSGER), CAMCOG-R and MMSE was used to assess concordance between cognitive and
      behavioral measures. RESULTS: Differences between the versions mainly involved
      object naming, items for verbal memory, such as the number of trials allowed, the
      imagery value of the words selected as targets or distractors, and the number of
      parallel versions. These differences were eliminated by adapting and harmonizing
      the various versions of the ADAS-Cog. Thereafter, only small differences between
      the different countries were found, and patterns of correlation between ADAS-Cog,
      and the NOSGER, CAMCOG-R and MMSE were consistent. CONCLUSIONS: The study
      underlines the need to use harmonized versions of instruments for rating dementia
      in multinational studies. The findings indicate that the harmonization of the
      ADAS-Cog was successful.

PMID- 14716699
TI  - Knowledge of Alzheimer's disease in four ethnic groups of older adults.
AB  - OBJECTIVES: The present study evaluated knowledge of Alzheimer's disease (AD) in
      four ethnic groups of older adults. METHODS: Ninety-six Anglo, 37 Latino, 30
      Asian, and 30 African American older adults completed a short survey about AD.
      RESULTS: Results indicated that Anglo older adults are significantly more
      knowledgeable about AD than African American, Asian, and Latino older adults.
      Level of education partially accounted for differences in knowledge of AD between
      Latino to Anglo older adults. After controlling for age, number of years of
      speaking English was associated with knowledge of AD in Asian older adults.
      CONCLUSIONS: The results suggest that certain ethnic minority groups do not have
      sufficient information about AD, and this may explain the lack of AD service use
      by minorities. Extensive evaluation of barriers to knowledge of AD is needed in
      order to specifically target minority groups and educate them about AD and the
      importance of early intervention.

PMID- 14716700
TI  - A multinational, randomised, 12-week study comparing the effects of donepezil and
      galantamine in patients with mild to moderate Alzheimer's disease.
AB  - OBJECTIVES: To compare directly, in the same patient cohort, the ease of use and
      tolerability of donepezil and galantamine in the treatment of Alzheimer's disease
      (AD), and investigate the effects of both treatments on cognition and activities
      of daily living (ADL). METHODS: Patients with mild to moderate AD from 14
      European centres were randomised to receive open-label donepezil (up to 10 mg
      once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to
      the approved product labelling. Physicians and caregivers completed
      questionnaires rating satisfaction with treatment/ease of use in daily practice.
      Secondary assessments were the ADAS-cog, the MMSE, and the DAD scale to assess
      ADL. Tolerability was evaluated by reporting adverse events (AEs). RESULTS: Both
      physicians and caregivers reported significantly greater overall
      satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n =
      56) at weeks 4, 12, and endpoint (week 12 LOCF; all p-values <0.05).
      Significantly greater improvements in cognition were also observed for donepezil
      versus galantamine on the ADAS-cog at Week 12 and endpoint (p-values <0.05). ADL
      improved significantly in the donepezil group compared with the galantamine group
      at weeks 4, 12, and endpoint (p-values <0.05). Most AEs were mild to moderate,
      however, 46% galantamine-treated patients reported gastrointestinal AEs vs 25%
      donepezil patients. CONCLUSIONS: Physician and caregiver ease of use/satisfaction
      scores, and assessments of cognition and ADL, showed significant benefits for
      donepezil compared with galantamine in this direct comparative trial. Both
      treatments were well tolerated, with more gastrointestinal AEs reported for
      galantamine vs donepezil.

PMID- 14716701
TI  - Obesity and depressive symptoms in Chinese elderly.
AB  - OBJECTIVES: The main objective was to examine the association between obesity and
      depressive symptoms among Chinese elderly in Hong Kong. METHODS: Cross-sectional
      data on depressive symptoms and body mass index from 56 167 clients aged 65 or
      over who enrolled as members of Elderly Health Centres from July 1998 to December
      2000 were analysed using multiple logistic regression with adjustment of
      potential confounders. RESULTS: Among 18 750 men and 37 417 women, the prevalence
      [95% confidence interval (CI)] of depressive symptoms (based on the Geriatric
      Depression Scale) was 4.9% (4.6-5.2%) and 7.9% (7.6-8.1%) respectively (p <
      0.001). The prevalence of obesity (by World Health Organisation Asian standard:
      body mass index > or =25.0) in women was significantly higher than that of men
      (42.1% (41.6-42.7%) vs 36.6% (35.9-37.3%), p < 0.001). Obese men and women were
      about 20% less likely to suffer from depressive symptoms compared with those with
      normal weight after adjustment for confounders, with odds ratios (95% CI) of 0.82
      (0.69-0.97) and 0.78 (0.71-0.86) respectively. Negative linear trends were
      observed between depressive symptoms and BMI categories in both sexes, and women
      showed a greater slope and stronger statistical significance than men.
      CONCLUSIONS: Both obese elderly men and women in Hong Kong were less likely to
      suffer from depressive symptoms than those of normal weight. The results support
      the 'jolly fat' hypothesis previously restricted to men, and extend the
      hypothesis to female elderly. Chinese traditional culture and positive values
      towards obesity may be protective against depressive symptoms.

PMID- 14716702
TI  - Validity of the Telephone Interview for Cognitive Status (TICS) in post-stroke
      subjects.
AB  - BACKGROUND: Cognitive impairment and dementia are very common after stroke.
      Telephone screening has potential advantages for clinical follow-up and
      population-based research in this group. We wished to test the validity of the
      Telephone Interview for Cognitive Status (TICS) for cognitive testing in post
      stroke subjects. METHODS: Cognitive function in stroke outpatients was assessed
      using the R-CAMCOG (a modification of the cognitive part of the Cambridge
      Examination for Mental Disorders of the Elderly, for use in stroke subjects)
      along with the TICS and a modified version, the TICSm. The tests were
      administered in random order. A cut-off point of 33 on the R-CAMCOG was used to
      define post-stroke dementia. RESULTS: Sixty-four patients with a median age of 72
      years were assessed. The Pearson correlation coefficients between the R-CAMCOG
      and the TICS and TICSm were 0.833 and 0.855 (both p <0.001) respectively. Twenty
      four (38%) patients met R-CAMCOG criteria for post-stroke dementia. The area
      under the ROC curve for both the TICS and TICSm was 0.94. Using a cut-off of 28
      or less on the TICS produced a sensitivity of 88% and a specificity of 85% for
      the diagnosis of post-stroke dementia. For the TICSm a cut-off of 20 or lower
      produced a sensitivity of 92% and a specificity of 80%. CONCLUSIONS: The TICS and
      TICSm telephone questionnaires are practicable and valid methods of assessing
      cognitive function in community outpatients following stroke. Scores of < or =28
      and < or =20 respectively carry good sensitivity and specificity for the
      diagnosis of post-stroke dementia.

PMID- 14716703
TI  - The 15-item Geriatric Depression Scale (GDS-15) detects changes in depressive
      symptoms after a major negative life event. The Leiden 85-plus Study.
AB  - BACKGROUND: The 15-item Geriatric Depression Scale (GDS-15) is a widely used
      screening instrument for depressive symptoms in the elderly, but its ability to
      detect alterations in depressive symptoms over time has not been established.
      OBJECTIVE: To assess the change of the GDS-15 score after a major negative life
      event. METHODS: Within the Leiden 85-plus Study, we prospectively followed a
      population-based cohort of 599 subjects from 85 years onwards. The GDS-15 was
      applied annually to participants with a Mini-Mental State Examination (MMSE)
      score above 18 points. The change in GDS-15 score of 32 subjects who had lost
      their partner during follow-up was compared with a control group of 32 subjects
      who had not lost their partner, matched for age, sex, and initial GDS-15 score.
      RESULTS: At baseline, 241 subjects lived together with a partner. During a mean
      follow-up of 3.2 years, 55 participants (23%) lost their partner. Of those, 32
      subjects completed the GDS-15 before and after the loss of their partner. All
      subjects reported the bereavement to be a major negative life event. The mean
      increase of the GDS-15 score after the death of a partner was 1.2 points (paired
      t-test, p = 0.013). This was significantly higher than the mean change of -0.06
      points in the matched control group (independent t-test, p = 0.032), and
      independent of sex, level of education, pre-bereavement GDS-15 score, and time
      period since the loss of a partner. CONCLUSION: This study shows that the GDS-15
      detects change in depressive symptoms after loss of a partner, a negative life
      event that is the most important risk factor for depression in the elderly.
      Therefore, it may be concluded that the GDS-15 has the ability to measure
      longitudinal alterations in depressive symptomatology.

PMID- 14716704
TI  - Do caregiver management strategies influence patient behaviour in dementia?
AB  - OBJECTIVES: Little is known about the effectiveness of caregiver management
      strategies on the functioning of the demented patient. However, identification of
      specific caregiver strategies may provide useful information on the management
      and manifestation of behavioural problems in dementia. METHODS: Ninety-nine
      patients with dementia and their informal caregivers were followed up for one
      year. Interviews were used to assess differences in caregiver management
      strategies. Behavioural disturbances in the patient were measured with the
      Neuropsychiatric Inventory (NPI). Repeated measures analysis were carried out to
      investigate the relationship between caregiver management strategies and patient
      behaviour. RESULTS: Three caregiver management strategies were identified, based
      on whether caregivers accepted, or not, the caregiving situation and dementia
      related problems. Caregivers characterized by non-acceptance were typified as
      'Non-adapters'; caregivers characterized by acceptance were further subdivided
      into two groups typified as 'Nurturers' and 'Supporters'. Caregiver
      characteristics such as sex, education and personality were important
      determinants of management strategies. MANOVA showed that non-adapters reported
      significantly more hyperactivity symptoms in patients and felt less competent
      than did supporters. CONCLUSIONS: Caregiver management strategies would appear to
      be associated with behavioural problems in dementia, and are important in
      predicting patient behaviour and caregiver burden. Intervention programmes should
      aim at teaching caregivers adequate management strategies.

PMID- 14716705
TI  - Double-blind comparative study of the action of repeated administration of
      milnacipran versus placebo on cognitive functions in healthy volunteers.
AB  - OBJECTIVE: The principal objective was to compare the effects of milnacipran, an
      antidepressant characterized by a dual-action on serotonin and noradrenaline
      reuptake, with placebo on memory, attention and psychomotor performance in
      healthy volunteers. The secondary objective was to evaluate the effects of
      milnacipran on mood, anxiety and vigilance in these subjects. METHODS: In a
      double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was
      administered during two periods of 7 days separated by a washout period of 7
      days. Memory tests (recall of words, images and coloured bars), tests to evaluate
      attention and vigilance (squares test, critical flicker fusion test and choice
      reaction time test) and visual analogue scales for affect and sleep were used.
      RESULTS: There were no significant differences between milnacipran and placebo
      groups with respect to the psychomotor functions tested. No differences were
      observed in the Norris scales for vigilance, anxiety or satisfaction or in the
      sleep questionnaire (sleep latency, sleep quality and waking). CONCLUSION:
      Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had
      no effects on cognitive functions.

PMID- 14716706
TI  - The treatment of depression with different formulations of venlafaxine: a
      comparative analysis.
AB  - Venlafaxine is the first of a group of antidepressants that show dual reuptake
      inhibition of serotonin and noradrenaline (SNRIs). Originally marketed in an
      immediate release (IR) formulation a microencapsulated, extended release (XR)
      formulation is now available. Significant differences exist between these two
      formulations with respect to pharmacokinetic parameters which have an impact on
      clinical use. The XR has lower maximum plasma concentrations (Cmax) and achieves
      these at a later time (higher Tmax). The longer apparent elimination half-life of
      the drug after single XR doses suggests that it is suitable for once daily dosing
      compared with the twice daily dosing regimen required by the IR formulation. With
      respect to antidepressant efficacy the XR formulation is equivalent to other
      marketed antidepressants and to the IR formulation. Consistent with its
      pharmacokinetic properties the use of the XR formulation is associated with less
      nausea and dizziness at the initiation of therapy. While in clinical usage XR
      might be expected to increase compliance with medication and to reduce
      discontinuation syndromes there are few comparative studies for which this has
      been evaluated. The XR formulation of venlafaxine is no worse than the IR form
      with respect to tolerability and offers some benefits to patients in terms of
      ease of use. On the other hand there does not appear to be any increase in the
      efficacy of the active agent.

PMID- 14716707
TI  - No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor
      metabolizers treated with fluoxetine or nortriptyline.
AB  - The polymorphic enzyme cytochrome P450 CYP2D6 is involved in the metabolism of
      many antidepressants, including nortriptyline and fluoxetine. Some 7%-10%
      Caucasians have inactivating mutations in both alleles of the CYP2D6 gene, and
      are referred to as poor metabolizers (PMs). Several case reports and clinical
      studies suggest that CYP2D6 PMs are at a greater risk of developing adverse drug
      reactions (ADRs) on antidepressant medication than extensive metabolizers (EMs).
      However, few clinical trials have investigated whether CYP2D6 PM genotype is
      predictive of ADRs during antidepressant treatment. This paper explores the link
      between CYP2D6 genotype and antidepressant-associated ADRs in outpatients being
      treated for major depression with either nortriptyline or fluoxetine. Patients
      were randomized to fluoxetine (n=65) or nortriptyline (n=60) for the 6 week
      trial. CYP2D6 genotypes predicted that of these patients 115 were EM and the
      remaining 10 were PMs. ADRs attributed to antidepressant usage were recorded over
      the 6-week trial. Although the type of ADR was, as expected, different between
      drugs, the frequency of ADRs experienced did not differ significantly between the
      two antidepressants or between CYP2D6 PMs and EMs. In addition, the frequency at
      which PMs discontinued antidepressant medication was not noticeably different
      from EMs, although with only 10 PMs the study is under powered to detect moderate
      or small differences. These findings suggest that inability to efficiently
      metabolize antidepressants that are CYP2D6 substrates does not necessarily lead
      to increased occurrence of antidepressant-associated ADRs. Thus, for clinicians
      prescribing antidepressant monotherapy, CYP2D6 polymorphisms are probably not of
      relevance to antidepressant side effects and therapy.

PMID- 14716708
TI  - Paroxetine in the treatment of depressed patients with haematological malignancy:
      an open-label study.
AB  - OBJECTIVE: The efficacy and tolerability of paroxetine in the treatment of
      depressive disorders is well known, however, its efficacy and safety for the
      treatment of depression in patients with cancer has been poorly studied.
      Therefore this study was aimed at evaluating the efficacy and tolerability of
      paroxetine in the treatment of depressed patients with haematological malignancy
      (HM). METHOD: Fifty-two patients with major depressive disorder (MDD) based on
      DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a
      flexible-dose regime of paroxetine in combination with their chemotherapy or
      supportive pharmacotherapy. The treatment response was assessed at baseline, week
      2, week 4 and week 8 with the 17-item Hamilton rating scale for depression (HAM
      D17), the Montgomery Asberg depression rating scale (MADRS) and the clinical
      global impression-severity (CGI-S). Side effects were collected with reported
      adverse events and laboratory tests throughout the study period. RESULTS: 44.2%
      of 52 patients completed the 8 week trial. Scores on the HAM-D17, MADRS and CGI-s
      (last observation carried forward, LOCF) at baseline were significantly reduced
      with a mean reduction of 30.5%, 32.8% and 39.1%, respectively, after 8 weeks
      treatment with paroxetine. CONCLUSION: In this preliminary study, paroxetine was
      found to be effective and moderately tolerated in the treatment of depressed
      patients with HM, and the present study calls for a controlled study in this
      field to extend and form a framework on the psychopharmacological data in this
      field.

PMID- 14716709
TI  - In vitro microsomal metabolism of imipramine under conditions mimicking the in
      vivo steady-state situation.
AB  - A steady-state model is presented of the metabolism of imipramine. In this model,
      the N-demethylation and 2-hydroxylation rates of imipramine were measured with
      and without the presence of metabolites by using a tritium isotope of imipramine.
      At an imipramine concentration of 5 micromol/l, desipramine, in the concentration
      ratio 1:2, decreased the total metabolic rate by 70%. The 2-hydroxylation pathway
      was mainly inhibited, thereby increasing the N-demethylation pathway from 25% to
      62% in the presence of desipramine. The additional presence of 2-hydroxy
      imipramine did not change this situation. A study on the relative influence of
      CYP1A2 and 3A4 only revealed minor changes in the presence of desipramine. In
      conclusion, the presence of metabolites in metabolism studies undertaken in vitro
      may reflect the changes from the single- to the multiple-dose situation observed
      clinically and therefore constitute a better model for the clinical application
      of a drug.

PMID- 14716710
TI  - Nizatidine for the treatment of patients with quetiapine-induced weight gain.
AB  - It has been reported that nizatidine may reduce weight gain in schizophrenic
      patients on olanzapine treatment. Leptin has been reported to be associated with
      antipsychotic-induced weight gain. Thus, the purpose of the study was to evaluate
      whether nizatidine might be useful for the treatment of quetiapine-induced weight
      gain. Among the patients on the quetiapine monotherapy, 47 participated in the
      study for the two and half months of the open-label screening period. However, 28
      patients who gained considerable weight in this period entered the 8-week, double
      blind and placebo-controlled phase. These patients were randomly divided into two
      groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group
      II) for the 8-week double-blind phase. The patients were evaluated at the
      baseline and at week 8 with respect to the positive and negative syndrome scale,
      body mass index, weight and serum leptin levels. The mean weight and leptin
      levels exhibited modest increases in both groups for the open-label screening
      period. In the double-blind period, in group I, a minimal, but not statistically
      significant, decrease in weight was observed, with a mean of 1.0 +/- 0.6 kg. The
      weight increased in group II. The leptin levels decreased by a mean of 0.6 +/-
      0.6 ng/ml in group I, and increased by 1.0 +/- 0.9 ng/ml in group II. At
      evaluation at week 8, a trend toward statistical significance in the mean serum
      leptin levels between groups was detected. The results suggest that nizatidine
      treatment may stop but not reduce the weight gain and is correlated with leptin
      levels in patients with schizophrenia on quetiapine treatment.

PMID- 14716711
TI  - Acute and continuation risperidone monotherapy in mania.
AB  - BACKGROUND: The aim of this study was to assess the effectiveness and safety of
      risperidone monotherapy for acute and continuation treatment of mania. METHOD:
      Ninety-six DSM-IV acutely manic bipolar patients with a Young mania rating score
      (YMRS) of 20 or more entered this open, multicentre, 6-month study. Efficacy was
      assessed with the YMRS, the positive and negative syndrome scale (PANSS) and the
      clinical global impressions scale (CGI). Safety was assessed with the UKU side
      effect rating scale and with the Hamilton depression rating scale, for the
      assessment of a switch to depression. RESULTS: 80 patients (83.3%) completed the
      study. Using the last-observation-carried-forward analysis, risperidone produced
      highly significant improvements (p<0.0001) on the all efficacy measures from
      weeks 1 (YMRS) and 4 (PANSS and CGI) onwards, for a 6-month period. There was a
      significant increase in extrapyramidal side-effects by week 4 (p=0.015) and a
      significant decrease at the 6-month endpoint (p=0.027). Risperidone did not
      induce depressive symptoms, as mean HDRS scores actually improved (p<0.0001), and
      exacerbation of mania was rare (n=4, 4.2%). The mean dose of risperidone was 4.2
      mg/day. CONCLUSION: Monotherapy with risperidone is effective and well tolerated
      in acute and continuation treatment of mania. The results should be confirmed in
      randomized, double-blind clinical trials.

PMID- 14716712
TI  - Switching to quetiapine in patients with acute mania who were intolerant to
      risperidone.
AB  - This study evaluated the overall efficacy and tolerability of quetiapine in the
      treatment of inpatients with acute mania who are intolerant to risperidone in
      combination with a mood stabilizer. Eighteen patients completed this 3-week
      trial. The efficacy and tolerability was assessed upon admission, at baseline,
      and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global
      impression-severity (CGI-s) scores from the baseline to the endpoint, decreased
      by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients
      exhibited at least a 50% improvement in the YMRS and CGI-s scores by the end of
      the trial. Measurements taken through the Barnes akathisia rating scale (BARS),
      the Simpson-Angus rating scale (SARS) and the drug attitude inventory shortened
      version-10 (DAI-10) also showed significant improvement. This study suggests that
      quetiapine may hold promise as an alternative regimen that does not worsen the
      psychopathology, particularly for those vulnerable to the side effects of drugs,
      including atypical agents such as risperidone, in naturalistic treatment
      settings.

PMID- 14716713
TI  - Olanzapine treatment of eight adolescent patients with psychosis.
AB  - Although olanzapine is known as a widely used atypical antipsychotic there have
      been very few studies about its use in children and adolescents. Eight adolescent
      patients who were diagnosed as having schizophrenia or schizoaffective disorder,
      and treated with olanzapine are reported in this case series. The patients were
      followed-up for 17.5 weeks in the range 4-26 weeks. According to the CGI
      improvement assessment at the end of the follow-up period, three of eight cases
      were rated as very much or much improved, three as minimally improved and two as
      not improved. Olanzapine was well tolerated by the adolescents in this case
      series except for weight gain. Our results suggest that olanzapine may be an
      effective antipsychotic for some psychotic adolescents and during olanzapine
      trials weight gain. Should be monitored.

PMID- 14716714
TI  - Effect of glucose on tobacco withdrawal symptoms in recent quitters using
      bupropion or nicotine replacement.
AB  - RATIONALE AND OBJECTIVES: Glucose has been shown to alleviate the desire to smoke
      in abstaining heavy smokers and to increase 1-month abstinence rates on its own
      as well as when combined with nicotine patches. It is not known whether a single
      dose of glucose can provide additional withdrawal relief in patients who have
      already abstained for a period of time, and whether it can assist patients using
      bupropion. METHODS: Seventy-five volunteers from a smoking cessation clinic who
      maintained 1 week of validated continuous abstinence were randomized to receive
      four 3 mg dextrose or placebo (sorbitol) tablets. There were 31 bupropion and 44
      NRT users. Measures of desire to smoke and of five withdrawal symptoms were taken
      before taking the tablets, and then at 5 min intervals for 20 min. RESULTS:
      Despite low baseline ratings of withdrawal discomfort, glucose tablets
      significantly reduced irritability and hunger in bupropion users. Two other
      effects including reduction in composite withdrawal score approached but did not
      reach statistical significance. The effects emerged 10-15 min after taking the
      tablets. No glucose effect was detected in patients using NRT. CONCLUSIONS: A
      single dose of glucose taken after a week of sustained abstinence may reduce
      withdrawal discomfort in patients on bupropion. Further research is warranted in
      combining glucose and bupropion, and in opportunistic use of glucose tablets in
      tempting situations during a smoking cessation attempt.

PMID- 14716715
TI  - Recovery from chronic fatigue syndrome with modafinil.

PMID- 14716716
TI  - Different effects of selective serotonin reuptake inhibitors on a patient
      suffering from panic disorder.

PMID- 14716718
TI  - Statistical methodology in Alzheimer's disease research II. Proceedings of a
      conference. May 10-12, 2002, Lexington, Kentucky, USA.

PMID- 14716719
TI  - Genetic association studies in Alzheimer's disease research: challenges and
      opportunities.
AB  - Genetic association studies have identified important risk factors for
      Alzheimer's disease and other diseases. However, the ease with which these
      methods can be applied and the shear number of polymorphisms in the human genome
      has led to a well-characterized multiple comparison problem-given the number of
      genetic variants being tested, it is likely that many of the positive findings
      reported in the literature to date will prove to be false positive findings
      explained simply by random fluctuation in data and type I error. The disparity of
      findings in initial positive reports versus subsequent negative replication
      studies observed in the Alzheimer's disease literature underscores this problem.
      The problem of a high false positive rate can be addressed in part by using
      statistical correction for multiple comparisons in larger and statistically more
      powerful samples and in meta-analyses of smaller samples. National initiatives
      are now being considered to address this problem by encouraging sharing of
      genetic material. Of equal concern in planning future initiatives are
      methodological issues that are the domain of the epidemiologist. In fact, it is
      possible that disparate findings across case-control studies reported to date may
      be explained in part by problems in the design, analysis and interpretation of
      these studies. The involvement of epidemiologists may improve the situation in
      this regard. For example, population stratification bias, control selection bias
      and prevalent case bias can be minimized by careful study design and by
      appropriate statistical analysis. Regarding interpretation of case-control
      studies, a more careful consideration of the strength of evidence for a given
      genetic variant may help to temper enthusiasm for, or appropriately qualify,
      positive findings. Epidemiologists have well-developed causal criteria for this
      purpose. This paper reviews the current state of case-control studies of genetic
      variants in Alzheimer's disease from the epidemiological perspective. The problem
      of multiple comparisons and a high false positive rate is reviewed. The potential
      for bias in case-control studies of Alzheimer's disease is reviewed by way of
      example. Future initiatives to promote case-control studies of genetic variants
      in Alzheimer's disease can only benefit from increased awareness the tools of
      epidemiology.

PMID- 14716720
TI  - Family-based association tests for survival and times-to-onset analysis.
AB  - In this paper, we discuss family-based association test (FBATs) relating genetic
      data to survival and time-to-onset data. We show how the standard logrank and
      Wilcoxon statistics can be used with family data to develop tests of association.
      We prove that the FBAT-logrank approach can be identical to the proportional
      hazard approach discussed in Mokliatchouk et al. (2000). Further, using
      simulation studies, we compare the power of the logrank, Wilcoxon and an approach
      developed for censored exponential data (Euro J Hum Gen 2001; 9:301-306). Based
      on the results of the simulation study, we suggest rules of thumb about which
      statistics to use in a given situation. An application of all three tests to an
      Alzheimer study illustrates the practical relevance of our discussion.

PMID- 14716721
TI  - Population-based studies of AD: message and methods: an epidemiologic view.
AB  - Dementia is a growing public health problem because the numbers suffering the
      disease is increasing rapidly as the population ages. Over the past decade
      several longitudinal population-based studies were initiated and are still on
      going. These studies will provide valuable insight into the risk factors for, and
      progression of dementia. However, there are several design and statistical
      challenges that are unique to studying dementia in the population and that need
      to be addressed. These challenges include aspects of both ascertainment of
      disease and definition of exposure. To reduce bias from prospective epidemiologic
      studies, not only are new approaches to definition of disease and exposure
      needed, but new epidemiologic or statistical methods may be required as well.

PMID- 14716722
TI  - Incidence and mortality of Alzheimer's disease or dementia using an illness-death
      model.
AB  - We present an illness-death model for studying the incidence and the prevalence
      of Alzheimer's disease or dementia. We argue that the illness-death model is
      better than a survival model for this purpose. In this model the best choice for
      the basic time-scale is age. Then we present extensions of this model for
      incorporating covariates and taking account of a possible effect of calendar
      time. Calendar time is introduced via a proportional intensity model. We give the
      likelihood for a mixed discrete-continuous observation pattern from this model:
      clinical status is observed at discrete visit-times while the date of death is
      observed exactly or right-censored. The penalized likelihood approach allows to
      non-parametrically estimate the transition intensities. Application on the data
      of the Paquid study allows to produce estimates of the age-specific incidence of
      dementia together with mortality rates of both demented and non-demented
      subjects. Then the effect of calendar time and educational level are studied. Low
      educational level increases the risk of dementia. The risk of dementia increases
      with calendar time while the mortality of demented subjects decreases. The most
      likely explanation of this result seems to be in a shift in the diagnosis of
      dementia towards earlier stages of the disease prompted by a change in the
      perception of dementia and the arrival of new drugs.

PMID- 14716723
TI  - A shared random effect parameter approach for longitudinal dementia data with non
      ignorable missing data.
AB  - A significant source of missing data in longitudinal epidemiologic studies on
      elderly individuals is death. It is generally believed that these missing data by
      death are non-ignorable to likelihood based inference. Inference based on data
      only from surviving participants in the study may lead to biased results. In this
      paper we model both the probability of disease and the probability of death using
      shared random effect parameters. We also propose to use the Laplace approximation
      for obtaining an approximate likelihood function so that high dimensional
      integration over the distributions of the random effect parameters is not
      necessary. Parameter estimates can be obtained by maximizing the approximate log
      likelihood function. Data from a longitudinal dementia study will be used to
      illustrate the approach. A small simulation is conducted to compare parameter
      estimates from the proposed method to the 'naive' method where missing data is
      considered at random.

PMID- 14716724
TI  - Adjusting for non-ignorable verification bias in clinical studies for Alzheimer's
      disease.
AB  - A common problem for comparing the relative accuracy of two screening tests for
      Alzheimer's disease (AD) in a two-stage design study is verification bias. If the
      verification bias can be assumed to be ignorable, Zhou and Higgs have proposed a
      maximum likelihood approach to compare the relative accuracy of screening tests
      in a two-stage design study. However, if the verification mechanism also depends
      on the unobserved disease status, the ignorable assumption does not hold. In this
      paper, we discuss how to use a profile likelihood approach to compare the
      relative accuracy of two screening tests for AD without assuming the ignorable
      verification bias mechanism.

PMID- 14716725
TI  - Multivariate longitudinal models for complex change processes.
AB  - Longitudinal studies offer us an opportunity to develop detailed descriptions of
      the process of growth and development or of the course of progression of chronic
      diseases. Most longitudinal analyses focus on characterizing change over time in
      a single outcome variable and identifying predictors of growth or decline. Both
      growth and degenerative diseases, however, are complex processes with multiple
      markers of change, so that it may be important to model more than one outcome
      measure and to understand their relationship over time. We consider random
      effects models for the association between the trajectories of two outcomes over
      time, and then compare their properties to approaches based on separate ordinary
      least-squares estimates of change. We then illustrate with an example from the
      Religious Orders Study, a longitudinal cohort study of more than 900 members of
      Catholic religious orders who have had up to eight annual clinical examinations.

PMID- 14716726
TI  - Test bias in a cognitive test: differential item functioning in the CASI.
AB  - Assessment of test bias is important to establish the construct validity of
      tests. Assessment of differential item functioning (DIF) is an important first
      step in this process. DIF is present when examinees from different groups have
      differing probabilities of success on an item, after controlling for overall
      ability level. Here, we present analysis of DIF in the Cognitive Assessment
      Screening Instrument (CASI) using data from a large cohort study of elderly
      adults. We developed an ordinal logistic regression modelling technique to assess
      test items for DIF. Estimates of cognitive ability were obtained in two ways
      based on responses to CASI items: using traditional CASI scoring according to the
      original test instructions as well as using item response theory (IRT) scoring.
      Several demographic characteristics were examined for potential DIF, including
      ethnicity and gender (entered into the model as dichotomous variables), and years
      of education and age (entered as continuous variables). We found that a
      disappointingly large number of items had DIF with respect to at least one of
      these demographic variables. More items were found to have DIF with traditional
      CASI scoring than with IRT scoring. This study demonstrates a powerful technique
      for the evaluation of DIF in psychometric tests. The finding that so many CASI
      items had DIF suggests that previous findings of differences between groups in
      cognitive functioning as measured by the CASI may be due to biased test items
      rather than true differences between groups. The finding that IRT scoring
      diminished the impact of DIF is discussed. Some preliminary suggestions for how
      to deal with items found to have DIF in cognitive tests are made. The advantages
      of the DIF detection techniques we developed are discussed in relation to other
      techniques for the evaluation of DIF.

PMID- 14716727
TI  - Reconsidering the odds ratio as a measure of 2x2 association in a population.
AB  - The odds ratio (OR) is probably the most widely used measure of 2x2 association
      in epidemiology, but it often produces results that are puzzling or misleading.
      Receiver operating characteristic (ROC) methods are used to take a fresh look at
      the OR and show where and why such puzzling results arise. When researchers
      choose to report a summary measure of association, the OR is one of many measures
      of association that might be considered, not one that should be considered the
      'gold standard' of 2x2 measures of association. In a randomized clinical trial
      with binary outcome for success, either the success or failure rates in treatment
      and control groups might be reported separately or the number needed to treat to
      achieve one extra success, to emphasize the cost of unnecessary treatment needed
      to achieve a success. In studies assessing reliability or heritability, we
      recommend the intraclass kappa. In studies in which one binary variable is
      assessed against a binary criterion, we recommend the weighted kappa.

PMID- 14716728
TI  - Selecting pre-screening items for early intervention trials of dementia--a case
      study.
AB  - Our goal was to review and extend statistical methods for discriminating between
      normal subjects and those with dementia or cognitive impairment. We compared six
      different methods to one constructed by expert opinion, in their brevity and
      predictive power. The methods include logistic regression and neural networks,
      with standard and least absolute shrinkage and selection operator (LASSO)
      variable selection, as well as decision trees with and without boosting. These
      methods were applied to the baseline data of a subgroup of subjects in a dementia
      study, using their screening interview items to predict their clinical diagnosis
      of normal or non-normal (cognitively impaired or demented). The derived models
      were then validated on a different subgroup of subjects in the same study who had
      the screening and clinical diagnosis two to five years later. Performance of
      different models was compared based on their sensitivity and specificity in the
      validation sample. Generally, the six statistical methods performed slightly to
      moderately better than the expert-opinion model. Neural networks generally
      performed better than the logistic and decision tree models. LASSO improved the
      performance of logistic and neural network models, but it eliminated few input
      variables in the neural network. The single decision tree performed at least as
      well as the standard logistic model, and with fewer items, making it an
      attractive pre-screening tool. Using the boosting option for decision trees did
      not substantially improve the performance. We recommend that for each situation,
      different methods of classification should be attempted to obtain optimal results
      for a given purpose.

PMID- 14716729
TI  - Designing a large prevention trial: statistical issues.
AB  - Recent research in Alzheimer's disease (AD) is centred about the early detection
      and prevention of this disease. Several recent moderate size clinical trials
      targeted at high risk cohorts have been designed along this theme. There have
      been few attempts to design a large trial to prevent this disease in elderly
      individuals at low risk for the disease. The purpose of this paper is to suggest
      a framework for designing a simple, large AD prevention trial. This framework
      uses a discrete time hazard model for decreasing the incidence of AD when
      participants are randomly assigned to one or more active prevention agents or
      placebo. This design allows for differential incidence among participants due to
      age, family history, genetic disposition, and ethnicity. It takes into account
      the length of the follow-up period, participant mortality, drop-outs, drop-ins,
      and loss to follow-up. This framework is illustrated by PREADVISE, a recently
      initiated large add-on prevention trial investigating the use of anti-oxidants
      for preventing AD among men enrolled in a even larger prostate cancer prevention
      study, SELECT.

PMID- 14716730
TI  - Analytical, practical and regulatory issues in prevention studies.
AB  - Prevention studies, as distinguished from studies investigating treatments for
      established disease, present some distinct challenges. Perhaps the most extensive
      experience with preventive agents is in the area of infectious diseases; vaccines
      have been extremely effective in preventing many such diseases. Vaccines have
      been, and continue to be, studied in other disease areas such as certain cancers,
      but as yet have not achieved success outside of infectious disease prevention.
      One obvious and important feature of prevention studies is that they enroll
      healthy individuals; thus such studies require particularly high standards for
      the safety of those enrolled (and those who might ultimately receive the product
      being tested). Prevention studies often need to be quite large, as the types of
      diseases most important to prevent tend to be uncommon. Large studies usually
      require simplified approaches; to ensure high quality of data on the key
      variables it may be necessary to compromise on the amount of data collected,
      frequency of data collection, and other aspects of trial design. The reliability
      of randomization and blinding may be especially important in these large studies,
      as bias could easily overwhelm the small effects that are usually sought. Often,
      biomarkers thought to indicate developing but as yet subclinical disease, will be
      important to evaluate; whether such markers can serve as primary endpoints in
      prevention studies has been a contentious issue in many contexts. Studies in
      older populations, such as those at risk for Alzheimer's Disease, raise
      challenges such as accounting for competing risks, and considering potential
      interactions of preventive agents with multiple medications often used by the
      elderly.

PMID- 14716731
TI  - The evaluation of disease modifying therapies in Alzheimer's disease: a
      regulatory viewpoint.
AB  - Several drugs have received marketing approval in this country for the treatment
      of dementia of the Alzheimer's type. Their approval has been based on clinical
      trial designs that do not permit a distinction to be made between an effect of
      the drug on the symptoms of that disease, and an effect on the pathophysiological
      mechanisms that underlie that disorder. The latter effect has been referred to as
      'disease-modifying.'In recent years there has been considerable interest in
      developing disease-modifying treatments for Alzheimer's disease (AD), using
      either specific clinical designs, or surrogate markers, such as brain imaging
      modalities. This paper outlines the regulatory framework governing how the Food
      and Drug Administration addresses new drug claims, the current basis for
      approving drugs for the treatment of AD, clinical trial designs that have been
      proposed as a means of demonstrating disease-modifying effects, a general and
      regulatory background to the use of surrogate markers in drug development, and,
      finally, views about the possible role of surrogate markers, especially brain
      imaging, as outcome measures in clinical trials intended to produce disease
      modifying effects in Alzheimer's Disease.

PMID- 14716732
TI  - A comparison of classification methods for differentiating fronto-temporal
      dementia from Alzheimer's disease using FDG-PET imaging.
AB  - Flurodeoxyglucose positron emission tomography (FDG-PET) is being explored to
      determine its ability to differentiate between a diagnosis of Alzheimer's disease
      (AD) and fronto-temporal dementia (FTD). We have examined statistical
      discrimination procedures to help achieve this purpose and compared the results
      to visual ratings of FDG-PET images. The methods are applied to a data set of 48
      subjects with autopsy confirmed diagnoses of AD or FTD (these subjects come from
      a multi-centre collaborative study funded by the National Alzheimer's
      Coordinating Center). FDG-PET images are composed of thousands of voxels (volume
      elements) so one is left with a situation where there are vastly more variables
      than subjects. Therefore, it is necessary to perform a data reduction before a
      statistical procedure can be applied. Approaches using both the entire image and
      summary statistics calculated on a number of volumes of interest (VOI) are
      examined. We performed the data reduction techniques of principal components
      analysis (PCA) and partial least-squares (PLS) on the entire image and then used
      linear discriminant analysis (LDA), quadratic (QDA) or logistic regression (LR)
      to classify subjects as having AD or FTD. Some of these methods achieve
      diagnostic accuracy (as assessed by leave-one-out cross-validation) that is
      similar to visual ratings by expert raters. Methods using PLS appear to be more
      successful. Averaging or using VOI data may also be helpful.

PMID- 14716733
TI  - Two macroscopic and microscopic brain imaging studies of human hippocampus in
      early Alzheimer's disease and schizophrenia research.
AB  - Among the many diseases that affect the hippocampus, a small yet highly important
      brain region responsible for memory and identity, Alzheimer's disease and
      schizophrenia are among the most devastating. We describe a two-stage, region-of
      interest based linear mixed model approach to the analysis of a longitudinal
      functional magnetic resonance (FMRI) study of human memory function under several
      drug challenges. We then describe a Monte Carlo approach to testing members of
      nested hierarchies of linear models in a stereological study of different types
      and locations of human hippocampal neurons. Last, we attempt to draw the
      attention of the biostatistical community interested in imaging neuroscience to
      the intriguing complexities of human hippocampal research in early Alzheimer's
      disease, schizophrenia and other brain diseases via brain imaging methods.

PMID- 14716734
TI  - Managing and analysing data from a large-scale study on Framingham Offspring
      relating brain structure to cognitive function.
AB  - At the Framingham Heart Study under separate research grant funding from the
      National Institute of Aging, NIH, we are gathering brain structure and cognitive
      information on the Framingham Offspring, creating one of the largest known data
      sets to assess changes in brain structure associated with normative ageing and
      cognitive decline. Subject recruitment, data collection, data management and
      statistical analysis require a collaborative integrated effort on the part of the
      Framingham project team. Here we describe this effort, as well as the various
      brain structure and cognitive function parameters we are now collecting. We are
      currently performing analyses of data collected through 2002, and we discuss the
      statistical issues arising relating brain structure parameters to cognitive
      function.

PMID- 14716735
TI  - Apolipoprotein-D: a novel cellular marker for HGPIN and prostate cancer.
AB  - BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN) is a putative
      pre-malignant lesion of the prostate. While apolipoprotein-D (Apo-D), an androgen
      regulated hydrophobic transporter protein, is expressed in prostate tumors, its
      expression in HGPIN is unknown. METHODS: Immunoreactivity for Apo-D and another
      androgen-regulated protein, prostate specific antigen (PSA), was investigated in
      64 radical prostatectomy tissues by video image analysis. RESULTS: Eighty two
      percent of prostatectomy specimens demonstrated moderate to strong Apo-D
      immunoreactivity in areas of HGPIN. In comparison, weak Apo-D immunoreactivity
      was observed in non-malignant areas in only 24% of specimens. The median (range)
      percentage cellular area of HGPIN immunopositive for Apo-D (9.7%, 0-42.9), and
      the cellular concentration of Apo-D (MIOD 3.1, 0-13.3), were intermediate between
      that of normal (area 0%, 0-53.5%, MIOD 0, 0-12.6) and early stage prostate cancer
      tissues (area 29.2%, 0-90.8%, MIOD 6.7, 0-28.1). This increase in Apo-D
      expression from non-malignant, through HGPIN to prostate cancer was statistically
      significant (P < 0.001), and contrasted with the decrease observed in PSA
      staining between adjacent areas of normal glands, HGPIN, and cancer (P = 0.026).
      CONCLUSIONS: The presence of high levels of immunoreactive Apo-D in HGPIN and
      prostate cancer, but not in non-malignant epithelial cells, is consistent with
      HGPIN being an intermediate lesion in the transition to prostate cancer, and
      suggests that cellular Apo-D expression is a marker of malignant transformation
      of the prostate.

PMID- 14716736
TI  - Response to sublethal heat treatment of prostatic tumor cells and of prostatic
      tumor infiltrating T-cells.
AB  - BACKGROUND: To investigate the possibilities offered by high intensity focused
      ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic
      cancer (CaP) cells react towards heat treatment and whether increased access to
      CaP cells by the immune system would be the result. METHODS: Heat/stress response
      of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry,
      Western blotting, and Atlas array. A heat-induced change in immune recognition
      was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release
      with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells
      either heated or untreated as stimulator cells. RESULTS: Transcription of 68 out
      of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells.
      Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, 
      78) was seen at the border zone of HIFU treatment. Remarkably, even untreated
      benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of
      heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78.
      Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but
      decreased Th2-cytokine (IL-4, -5, -10) release of TIL. CONCLUSIONS: HIFU
      treatment may alter the presentation of prostate tissue and tumor antigens and
      this presentation is most likely stimulatory. HSP-72/73 overexpression in
      untreated BPH may suggest a mechanism by which BPH can incite inflammation.

PMID- 14716737
TI  - Analysis of the inflammatory network in benign prostate hyperplasia and prostate
      cancer.
AB  - INTRODUCTION: The complexity of acute and chronic inflammatory processes may
      either lead to benign prostate hyperplasia (BPH) and/or prostate cancer.
      Obviously, various tissue cells are activated by chemokines via different
      chemotaxin receptors which then trigger subsequent processes in angiogenesis,
      cellular growth, and extravasation as well as neoplasia. METHODS: Using the
      surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma
      (PCA), we studied among others the expression of chemokines (Rantes, IL-8),
      chemotaxin receptors (CXCR-3 and -4, CCR-3, CCR-5), of matrixmetalloproteinases
      (MMP-2 and 9), of Toll-like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the
      inducible cyclooxygenase-2 (cox-2) by RT-PCR. Further support for the different
      properties of tissue from PCA was obtained using two different PCA cell lines
      (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis
      on IL-8, Il-6, and PGE(2) release. Cell lines were stimulated with either the
      tumor necrosis factor-alpha (TNF-alpha) and lipopolysacharide (LPS) over time. In
      addition to cytokine release, the quantification of mRNA by lightcycler for cox
      2, IL-6, and IL-8 was performed on these cell lines. RESULTS: Remarkable
      differences in expression were obtained by RT-PCR when BPH tissue versus PCA was
      analyzed. Expression of CXCR-1 after incubation with LPS and TNF-alpha showed
      time-dependent differences for androgen-sensitive LNCAP as compared to androgen
      resistant PC-3 cells. TNF-alpha incubation leads to a time-dependent induction of
      cox-2 expression unlike to activation with LPS. Differences with regard to cox-2,
      IL-6, and IL-8 expression were seen by quantitative lightcycler analysis.
      Significant differences were also observed when TL receptors 4, 5, 7, and 9 were
      analyzed which were significantly expressed in BPH- as compared to PCA-tissue.
      CONCLUSIONS: Our data clearly demonstrate that various inflammatory and cell
      biological cascades are involved which either lead to BPH or can be linked to the
      development of PCA. The exact cell biological mechanisms may provide novel
      therapeutic options in the treatment of both diseases.

PMID- 14716738
TI  - Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and
      promotes cell death in the LNCaP prostate cancer cell line.
AB  - BACKGROUND: Reduction of T to DHT by 5alphaR in the prostate enhances androgenic
      activity for most targets. Inhibition of 5alphaR activity with finasteride
      attenuates androgen action in men and animal models. The objective of this study
      was to compare and contrast the effects of a potent new 5alphaR inhibitor,
      dutasteride, with finasteride in the LNCaP prostate cancer cell line. METHODS:
      LNCaP cells were incubated for varying times with T or DHT in steroid-free medium
      in the absence or presence of increasing doses of dutasteride or finasteride and
      the effects on 5alphaR activity, PSA accumulation in the medium, and on cell
      proliferation were determined. Drug effects on apoptosis were investigated using
      Annexin V staining and a cell death ELISA assay. Effects of the drugs on AR
      ligand-binding activity and on AR protein levels were determined. RESULTS:
      Dutasteride inhibited (3)H-T conversion to (3)H-DHT and, as anticipated,
      inhibited T-induced secretion of PSA and proliferation. However the drug also
      inhibited DHT-induced PSA secretion and cell proliferation (IC(50) approximately
      1 microM). Finasteride also inhibited DHT action but was less potent than
      dutasteride. Dutasteride competed for binding the LNCaP cell AR with an IC(50)
      approximately 1.5 microM. High concentrations of dutasteride (10-50 microM), but
      not finasteride, in steroid-free medium, resulted in enhanced cell death,
      possibly by apoptosis. This was accompanied by loss of AR protein and decreased
      AR ligand-binding activity. Occupation of AR by R1881 partly protected against
      cell death and loss of AR protein. PC-3 prostate cancer cells, which do not
      contain AR, also were killed by high concentrations of dutasteride, as well as by
      50 microM finasteride. CONCLUSIONS: Dutasteride exhibited some inhibitory actions
      in LNCaP cells possibly related to 5alphaR inhibition but also had antiandrogenic
      effects at relatively low concentrations and cell death-promoting effects at
      higher concentrations. Finasteride also was antiandrogenic, but less than
      dutasteride. The antiandrogenic effects may be mediated by the mutant LNCaP cell
      AR. Promotion of cell death by dutasteride can be blocked, but only in part, by
      androgens.

PMID- 14716740
TI  - Functional and anatomical effects of hormonally induced experimental prostate
      growth: a urodynamic model of benign prostatic hyperplasia (BPH) in the beagle.
AB  - BACKGROUND: Benign prostatic hypertrophy (BPH) produces a variety of changes in
      the urodynamic pattern of micturition and is usually associated with high
      detrusor voiding pressure and poor urine flow-rate. In most previous experimental
      models, designed to simulate this condition, some degree of obstruction is
      immediately imposed by the technique employed to produce urethral occlusion.
      Consequently these models cannot reproduce the gradual onset of obstruction. In
      the present study a canine prostatic enlargement model, using 5alpha
      dihydrotestosterone (DHT) + 17beta-estradiol (E) was adapted in order to produce
      a more gradual onset of partial obstruction and impaired voiding. MATERIALS AND
      METHODS: Hormonally induced prostatic enlargement was produced using seven
      beagles, given DHT 75 mg/day together with E 0.75 mg/day for 28 days via an
      implantable pump. The functional effects of DHT + E treatment on micturition
      pressure/flow were measured in the conscious animal. Identical measurements were
      also made using a separate older group of five beagles with symptoms of BPH. In
      addition seven beagles similarly instrumented were used as controls. RESULTS:
      Pressure/flow studies show that DHT + E produced obstructive micturition,
      characterized by a significantly increased micturition detrusor pressure, from
      33.3 +/- 10.5 to 50.8 +/- 10.7 cmH(2)O and significantly decreased low urine flow
      rate from 8.6 +/- 2.1 to 6.9 +/- 0.9 ml/sec. Associated with the obstructive
      micturition, this treatment increased wet prostate weight from 11.9 +/- 2.5 to
      31.6 +/- 10.0 g. Prostate volume of the BPH beagles was 29.3 +/- 8.9 g.
      Morphologic studies show that DHT + E produced epithelial hyperplasia extending
      focally into the lumen. CONCLUSIONS: Hormonally induced prostate growth produced
      bladder obstruction, in terms of pressure/flow characteristics, that are
      analogous to BPH. It is suggested that this type of hormonal treatment can be
      used to create a model for the study of the effects of controlled increased in
      prostate growth and the development of BPH on micturition.

PMID- 14716739
TI  - Radioimmunotherapy of prostate cancer in human xenografts using monoclonal
      antibodies specific to prostate specific membrane antigen (PSMA): studies in nude
      mice.
AB  - BACKGROUND: Prostate specific membrane antigen (PSMA), expressed by virtually all
      prostate cancers is an ideal target for targeted therapy of prostate cancer.
      Radiolabeled J591 monoclonal antibody (MAb) binds with high affinity to an
      extracellular epitope of PSMA and localizes specifically in PSMA positive LNCaP
      tumors in vivo. METHODS: Pre-clinical radioimmunotherapy (RIT) studies using
      (131)I-huJ591 and (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic
      acid (DOTA)-huJ591 MAbs were studied in nude mice bearing LNCaP xenografts.
      RESULTS: A 15-90% reduction in mean tumor volume was observed after a single dose
      of (131)I-huJ591 (3.7-11.1 MBq) or (90)Y-DOTA-huJ591 (3.7-7.4 MBq). The median
      survival time increased 2-3 times relative to untreated controls. Multiple
      administrations of fractionated doses of (90)Y-DOTA-huJ591 were even more
      effective with minimal toxicity. Radiation dose to blood and tumor was higher
      with (90)Y than with (131)I. The maximum tolerated dose (MTD) is 5.55 MBq for
      (90)Y-DOTA-huJ591 and more than 11.1 MBq for (131)I-huJ591. For (90)Y-DOTA-huJ591
      at MTD, dose to the tumor was 2,753 cGy. CONCLUSIONS: In nude mice bearing PSMA
      positive tumors, radiation dose to the tumor with (90)Y-DOTA-J591 is greater for
      large tumors than with (131)I-J591. The theoretical and practical considerations
      strongly suggest that (90)Y-DOTA-huJ591 may be a suitable radiopharmaceutical for
      the treatment of prostate cancer.

PMID- 14716741
TI  - Amphiregulin expression in prostatic intraepithelial neoplasia and
      adenocarcinoma: a study of 93 cases.
AB  - BACKGROUND: Amphiregulin (AMP) is a heparin-binding glycoprotein that is
      structurally and functionally related to epidermal growth factor. Its effects are
      mediated by the tyrosine kinase activity of the epidermal growth factor receptor
      (EGF-R), and specific nuclear targeting sequences. AMP induces cell proliferation
      after androgen stimulation of human prostate cancer cell lines. An autocrine
      proliferative loop involving AMP, androgen, and EGF-R may, therefore, play a role
      in prostatic carcinogenesis. The purpose of this study was to compare the
      expression of AMP in benign prostatic epithelium, high-grade prostatic
      intraepithelial neoplasia (PIN), and adenocarcinoma. METHODS: We performed an
      immunohistochemical study of select sections from 93 radical prostatectomies
      performed at the Mayo Clinic between 1987 and 1991. All patients were previously
      untreated and found to have pathologic stage T2N0M0 adenocarcinoma after routine
      handling of surgical specimens. Affinity-purified polyclonal antibody directed
      against AMP was applied to tissue sections using the streptavidin-biotin method.
      For each case, the percentage of immunoreactive cells in benign epithelium, PIN,
      and adenocarcinoma was estimated in 10% increments. Intensity on a scale from 0
      (negative) to 3 (strongly immunoreactive) and pattern of expression (nuclear
      versus cytoplasmic) also were recorded. RESULTS: AMP immunoreactivity was present
      in benign prostatic epithelium, PIN, and prostatic adenocarcinoma in all cases.
      The mean percentage of AMP-immunoreactive cells was 53.8% in benign epithelium,
      65.9% in PIN, and 74.3% in cancer. Intensity was moderate in all cases. The
      pattern of expression was usually nuclear in benign epithelium (secretory and
      basal cells), and usually cytoplasmic or nuclear and cytoplasmic in PIN and
      adenocarcinoma. There were rare scattered immunoreactive cells in the stroma,
      ejaculatory duct epithelium, and urethral urothelium. Endothelial cells were
      invariably unstained. CONCLUSIONS: AMP expression in prostate increases
      progressively from benign epithelium to PIN and cancer. Increased expression of
      AMP may contribute to the development of prostatic adenocarcinoma. Predominantly
      nuclear staining was observed in benign epithelium, whereas cytoplasmic or
      nuclear and cytoplasmic staining was observed in PIN and adenocarcinoma. The
      differences in nuclear and cytoplasmic localization of immunoreactivity may
      reflect the presence of two pathways of activation, and hence varying biological
      functions of AMP.

PMID- 14716742
TI  - Use of the Gleason system in international comparisons of prostatic
      adenocarcinomas in blacks.
AB  - BACKGROUND: Comparisons of prostate cancer in blacks living in different
      countries can shed light on factors responsible for high rates of the disease
      among blacks in America. Since the prognostic value of the Gleason grading system
      is well established, we assessed agreement between pathologists in countries
      where black populations of the African Diaspora reside. METHODS: Three
      genitourinary pathologists at hospitals in Nigeria, Jamaica, and the US
      independently assessed sextant biopsies from 12 patients. Gleason sum and
      percentage involvement were recorded, and a percent-weighted average calculated.
      Agreement under different groupings was evaluated using the kappa statistic
      generalized to three raters. RESULTS: Agreement was significant for individual
      sums (kappa = 0.3317, P = 0.0173), sums grouped as well (2-4), moderately (5-6),
      and poorly differentiated (7-10) (kappa = 0.2437, P < 0.0001) and other
      groupings. Agreement between at least two raters was 91.7-100%; complete
      agreement was 41.7-66.7%. CONCLUSIONS: The Gleason system is feasible and
      practical for international studies of prostate cancer among blacks from
      contrasting environments.

PMID- 14716743
TI  - Modulation of phenotype of human prostatic stromal cells by transforming growth
      factor-betas.
AB  - BACKGROUND: We investigated the effects of transforming growth factor (TGF)-betas
      on morphological and receptor phenotypes, as well as proliferation of four
      currently established human prostatic myofibroblast cell lines and one
      commercially available prostatic stromal cell line. METHODS: The effects of TGF
      betas on morphological changes and proliferation of the cells were studied by
      immunohistochemistry and bromodeoxyuridine assay, respectively. The expression of
      alpha 1-receptor subtypes was measured by real time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) and the radioligand binding
      assay for the receptors was also performed. RESULTS: TGF-betas 1, 2, and 3
      induced expression of desmin and myosin of cells of the established cell lines,
      and significantly inhibited their growth. The alpha 1a-receptor was expressed
      only in the commercially available cell line and alpha 1b and 1d, in all cell
      lines. TGF-beta 1 suppressed the expression of all three subtypes of the alpha 1
      receptor. The binding sites of cells of all the cell lines were reduced by
      treatment with this growth factor. CONCLUSIONS: TGF-betas may induce human
      prostatic stromal cells to express the smooth muscle phenotype and inhibited
      their growth. However, the growth factor reduced the binding sites of the
      receptor and suppressed mRNA expression of its subtypes, suggesting that
      morphological and receptor phenotypes may be regulated via more than one pathway
      by TGF-beta(s).

PMID- 14716744
TI  - CD24 expression is a significant predictor of PSA relapse and poor prognosis in
      low grade or organ confined prostate cancer.
AB  - BACKGROUND: The prognostic impact of tumor grading and staging is markedly
      reduced in organ confined or moderately differentiated prostate cancer, which
      underscores the importance of new prognostic markers. Evaluating public
      expression data of prostate cancer, we found an upregulation of the candidate
      gene CD24. METHODS: We examined immunohistochemically the expression of CD24
      protein in 31 nodal metastases and 102 adenocarcinomas of the prostate and
      correlated our findings to clinicopathological parameters. RESULTS: CD24
      expression was found in 48% of primary prostate cancer cases and in 68% of lymph
      node metastases. Kaplan Meier curves and Cox regression analysis showed that CD24
      expression was strongly linked to significantly earlier disease progression
      (relative risk = 3.2), which was especially pronounced in organ confined, or
      moderately differentiated primary prostate tumors. CONCLUSIONS: We conclude that
      CD24 is an important prognostic tissue marker for prostate cancer which could
      help to define patients of low or high risk of recurrence.

PMID- 14716745
TI  - Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in human
      prostate.
AB  - BACKGROUND: The growth and dissemination of tumors has been associated with
      angiogenesis, which is regulated by a group of polypeptide factors including
      vascular endothelial growth factor-C (VEGF-C). VEGF-C binds its receptor,
      vascular endothelial growth factor receptor-3 (VEGFR-3) to promote growth of
      tumor-associated lymphatic vessels. METHODS: In this study, microarray technology
      was used to build tissue arrays of normal prostate, benign prostate hyperplasia
      (BPH) and prostate carcinomas (PCa) using tissues from 640 patients. Slides were
      sectioned and stained with a polyclonal antibody to VEGFR-3 using a standard
      immunoperoxidase method and digitized. Immunoreactivity was scored using a 0-3+
      semiquantitation scoring system for both intensity and percentage. The sum index
      was obtained by totaling the scores. RESULTS: VEGFR-3 is expressed in normal
      prostate, BPH, and PCa, but VEGFR-3 expression is up-regulated in PCa. We also
      found that VEGFR-3 is correlated with pre-operative prostate-specific antigen
      (Pre-PSA), Gleason score, and lymph node metastasis. The recurrence-free 5-year
      survival in cases with lower sum index (0-3) was significantly higher than that
      in cases with higher sum index (4-6) (77.3, 69.6%, respectively, P = 0.037) by
      Kaplan-Meier actuarial model. CONCLUSIONS: Our data suggest that VEGFR-3
      expression is associated with tumor progression and may play an important role in
      facilitating lymphatic spread of PCa; high-level of VEGFR-3 expression in
      prostate cancer cells increases the risk of biochemical recurrence in prostate
      cancer patients treated by radical prostatectomy.

PMID- 14716746
TI  - Comparative analysis of prostate-specific membrane antigen (PSMA) versus a
      prostate-specific membrane antigen-like gene.
AB  - BACKGROUND: Currently prostate-specific membrane antigen (PSMA) is showing
      promise both as an imaging and therapeutic target for occult prostate cancer
      metastases. First generation antibodies against PSMA are used for the FDA
      approved Prostascint trade mark monoclonal antibody scan and second generation
      antibodies are being developed for therapeutic targeting as well as imaging 1.
      However, there have been reports describing PSMA expression in non-prostatic
      tissues including kidney, liver, and brain. As we had previously showed the
      existence of a human PSMA homolog, we set out to determine if this non-prostatic
      expression was due to expression of the PSMA or another gene. MATERIALS AND
      METHODS: The PSMA homolog (PSMA-like) cDNA was cloned by screening a liver cDNA
      library. mRNA expression of the PSMA and PSMA-like genes was determined via
      Northern blot analysis using two different probes and protein expression
      confirmed in some tissues via Western blot analysis. Transcriptional regulation
      of the two genes was examined using reporter constructs driving luciferase
      expression. RESULTS: The PSMA-like gene possesses 98% identity to the PSMA gene
      at the nucleotide level and is expressed in kidney and liver under the control of
      a different promoter to the PSMA gene. The PSMA gene is expressed in several
      human tissues and is most abundant in the nervous system and the prostate.
      CONCLUSION: The non-prostatic expression of PSMA should be taken into
      consideration when designing clinical strategies targeting PSMA.

PMID- 14716747
TI  - Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in
      children suffering from autoimmune diseases.
AB  - The aim of the present study was to compare the effect produced by juvenile
      rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of
      acetyl salicylic acid (ASA) and its metabolites in children with autoimmune
      diseases (AD). METHODS: A prospective, open labelled study was performed in 17
      children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg
      orally. The pharmacokinetics of ASA and its metabolites were determined. The
      blood and urine levels of each salicylate collected during 24 h were measured by
      HPLC. A group of 15 healthy teenage volunteers was included as a control group.
      RESULTS: The maximum plasma concentration, half-life time, area under the curve
      and the amount of salicylates excreted were statistically different between the
      JRA and the RF groups, as well as between the RF group and the controls, however,
      there were no significant differences between the JRA group and the controls.
      CONCLUSIONS: Dosage schemes must be adjusted for JRA patients, since the half
      life in these patients is longer than in RF patients. However, due to ample
      variability of pharmacokinetic parameters it is recommended that dose schemes are
      individualized on the type of autoimmune disease considered.

PMID- 14716748
TI  - Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo
      evaluation.
AB  - The objective of this study was to prepare a transdermal delivery system (TDS)
      for zidovudine (AZT) with a combination of menthol and oleic acid as penetration
      enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo
      as well as in vivo permeation across rat skin. It was found that AZT in gel
      formulation was stable in both refrigerated as well as accelerated stability
      conditions for 3 months and further, the gel did not significantly retard the
      permeability of AZT across the skin in comparison with solution formulation. Ex
      vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm(-2) h(-1),
      which is sufficient to achieve therapeutic plasma concentrations. Intravenous
      pharmacokinetic parameters of AZT in rats were determined and used together with
      ex vivo flux data to generate theoretical plasma profiles of AZT and compared
      with plasma concentrations achieved after application of TDS. Further, steady
      state plasma concentrations of drug following multiple applications of TDS were
      determined and good correlations between ex vivo and in vivo data were observed.
      In addition, the combination of penetration enhancers used at 2.5% w/w in this
      study proved efficient in achieving sufficient enhancement in the transdermal
      permeability of AZT across rat skin with reduced skin irritation potential when
      compared with individual penetration enhancers at higher concentrations.

PMID- 14716749
TI  - Comparative evaluation of digoxin concentrations determined by three assay
      systems: TDx, IMx and OPUS.
AB  - Digoxin concentrations measured by three automated immunoassay systems, i.e.
      OPUS, TDx and IMx assays, were compared in order to evaluate precision and
      accuracy performance, and data compatibility. Coefficients of variation for all
      methods in within-run and between-run precision were less than 10% at weighed-in
      concentrations of 0.545, 1.090 and 2.180 ng/ml. The accuracy relative to the
      three weighed-in concentrations ranged from 97% to 123% for all methods. One
      hundred and three plasma samples from 60 patients receiving digoxin were used to
      evaluate the data compatibility. Digoxin concentrations measured by the three
      immunoassay systems correlated well with one another. These results suggest that
      there are few problems when switching between digoxin assay methods, and that IMx
      and OPUS are more useful than TDx because they do not require sample
      pretreatment. The digoxin concentrations of the plasma samples from one patient
      receiving both digoxin and potassium canrenoate were investigated as a case
      report. The digoxin concentrations measured by TDx and IMx became higher than
      those measured by OPUS after starting the combination treatment. In another
      patient suffering from bilirubinaemia, the digoxin concentrations measured by TDx
      or IMx were higher than those measured by OPUS. These results suggest that OPUS
      has a higher specificity for measuring the plasma digoxin concentrations compared
      with TDx or IMx.

PMID- 14716750
TI  - Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs
      systemic administration of amifostine.
AB  - PURPOSE: Amifostine is a prodrug in which selectivity is largely determined by
      the preferential formation and uptake of its cytoprotective metabolite, WR-1065,
      in normal tissues as a result of differences in membrane-bound alkaline
      phosphatase activity. It was hypothesized that amifostine may be a good candidate
      for regional drug delivery to the liver because of its large hepatic extraction
      and total body clearance. METHODS: Rat livers were implanted with Walker-256
      tumors. The tumor-bearing rats received 15 min infusions of amifostine (200
      mg/kg) via the portal vein or the femoral vein. WR-1065 concentrations in the
      blood, liver and tumor were measured at various times. RESULTS: The WR-1065 tumor
      portal dosing AUC15-60 was 40% of systemic dosing, and tumor concentrations
      following portal dosing were one-fifth of that following systemic dosing. The
      portal dosing WR-1065 liver AUC15-60 was 60% higher than the values for systemic
      dosing. The liver/tumor concentration ratios of WR-1065 following portal dosing
      were up to 8-fold higher than the ratio following systemic administration.
      Unfortunately, systemic exposure to WR-1065 was greater following portal vs
      systemic amifostine. CONCLUSIONS: Amifostine may provide increased liver
      protection and decreased tumor protection from radio- or chemotherapy when
      administered by the portal vein. However, portal dosing also increases systemic
      exposure to WR-1065, which is associated with hypotension.

PMID- 14716751
TI  - In vitro investigation on the impact of the surface-active excipients Cremophor
      EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam.
AB  - The impact of the surface-active formulation ingredients Cremophor EL, Tween 80
      and Solutol HS 15 on the intrinsic clearance (Clint) of midazolam (MDZ) was
      investigated in rat hepatocytes and microsomes. In rat hepatocytes with 0.003%,
      0.03% and 0.3% (w/v) Solutol HS 15 already present in the incubation medium, the
      Clint was significantly reduced in a dose-dependent manner by about 25%, 30% and
      50%, respectively. In the presence of Cremophor EL and Tween 80 a significant
      reduction in Clint by about 30% and 25%, respectively, was observed at 0.03%
      surfactant concentration. At 0.3% of Cremophor EL and Tween 80, Clint was reduced
      by about 50% and 20%, respectively. A reduction in Clint was also observed in
      experiments with rat liver microsomes. At surfactant concentrations up to 0.03%,
      cytotoxicity assays (lactate dehydrogenase release, adenosine triphosphate
      content) as well as light microscope investigations did not reveal any cytotoxic
      impact of the surfactants on the hepatocyte monolayer. A potential interaction of
      the surfactants with biological membranes was determined using
      phosphatidylcholine-cholesterol liposomes loaded with self-quenching
      concentrations of carboxyfluorescein. No marked release of carboxyfluorescein
      from the liposomes (that would be an indication for a surfactant-dependent
      disruption of membrane integrity) was observed up to concentrations of 0.03% of
      the different surfactants. It is concluded that cytochrome P450 3A mediated
      metabolism of MDZ seems to be prevented by all surfactants at concentrations
      above 0.03%. In our experiments the surfactants did not show toxic effects at
      concentrations that resulted in a decreased Clint of MDZ. Thus, a direct
      inhibition of the metabolizing enzymes, a molecular interaction with the
      microsomes as well as an alteration of membrane properties that did not yet
      result in a release of LDH have to be taken into consideration as reasons for the
      observed changes in the metabolism of MDZ.

PMID- 14716752
TI  - A clinically comprehensive ethical framework for offering and recommending cancer
      treatment before and during pregnancy.

PMID- 14716753
TI  - Smoking causes colon carcinoma.

PMID- 14716754
TI  - Human papillomavirus infections: truth or consequences.

PMID- 14716755
TI  - Chemotherapy-induced neutropenia: risks, consequences, and new directions for its
      management.
AB  - Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host
      protective mechanisms and limiting the doses of chemotherapy that can be
      tolerated. Neutropenia, the most serious hematologic toxicity, is associated with
      the risk of life-threatening infections as well as chemotherapy dose reductions
      and delays that may compromise treatment outcomes. The authors reviewed the
      recent literature to provide an update on research in chemotherapy-induced
      neutropenia and its complications and impact, and they discuss the implications
      of this work for improving the management of patients with cancer who are treated
      with myelosuppressive chemotherapy. Despite its importance as the primary dose
      limiting toxicity of chemotherapy, much concerning neutropenia and its
      consequences and impact remains unknown. Recent surveys indicate that neutropenia
      remains a prevalent problem associated with substantial morbidity, mortality, and
      costs. Much research has sought to identify risk factors that may predispose
      patients to neutropenic complications, including febrile neutropenia, in an
      effort to predict better which patients are at risk and to use preventive
      strategies, such as prophylactic colony-stimulating factors, more cost
      effectively. Neutropenic complications associated with myelosuppressive
      chemotherapy are a significant cause of morbidity and mortality, possibly
      compromised treatment outcomes, and excess healthcare costs. Research in
      quantifying the risk of neutropenic complications may make it possible in the
      near future to target patients at greater risk with appropriate preventive
      strategies, thereby maximizing the benefits and minimizing the costs.

PMID- 14716756
TI  - Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project:
      twelve-year observations concerning lobular carcinoma in situ.
AB  - BACKGROUND: The current report represents a 12-year clinicopathologic update of
      an earlier 5-year analysis of 180 patients with lobular carcinoma in situ (LCIS)
      who were treated with local excision and subsequent surveillance only. METHODS:
      Nineteen pathologic characteristics of LCIS were assessed as potential predictors
      of invasive and noninvasive ipsilateral breast tumor recurrence (IBTR) and
      contralateral breast tumor recurrence (CBTR) as well as mortality. RESULTS:
      Overall, only 26 IBTRs (14.4%) and 14 CBTRs (7.8%) were observed. Nine IBTRs
      (5.0% of the total cohort) and 10 CBTRs (5.6% of the total cohort) were invasive
      carcinomas. Eight of 9 IBTRs (88.9%) and 6 of 8 invasive CBTRs (75%) that had
      histologic sections available for review were of the lobular invasive type.
      Ninety-six percent of all IBTRs and 100% of invasive IBTRs occurred within the
      same site as the index LCIS. The numbers of invasive IBTRs were comparable within
      and after 5 years (5 invasive IBTRs vs. 4 IBTRs). Recurrences of invasive CBTR
      occurred later than recurrences of invasive IBTR, with 70% of invasive CBTRs
      recognized after 5 years compared with 44% of invasive IBTRs. It was found that
      Grade 2-3 LCIS was significantly predictive for invasive IBTR when combined with
      the number of recurrences of ductal carcinoma in situ (DCIS) alone or with LCIS.
      Only 2 patients in the cohort (1.1%) succumbed to breast carcinoma; 1 patient had
      a prior invasive IBTR, and the other patient had an invasive CBTR. The reasons
      for the lower frequency of invasive recurrences and the higher proportions of the
      lobular invasive phenotype than noted by others are discussed along with the
      impact of the findings on the nomenclature, precursor nature, and treatment of
      LCIS. CONCLUSIONS: LCIS is a more indolent form of in situ breast carcinoma than
      DCIS, with which it shares other features of its natural history, particularly
      very low mortality rates. There is no compelling reason to surgically treat LCIS
      other than conservatively. The values of other adjuvant modalities in the
      management of LCIS are discussed. The authors acknowledge that their findings are
      based on relatively few events and, even at 12 years, may be regarded as
      "preliminary". Nonetheless, their findings may reflect the true biologic nature
      of LCIS.

PMID- 14716757
TI  - Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicenter study.
AB  - BACKGROUND: Vacuum-assisted breast biopsy (VAB) can replace surgical biopsy for
      the diagnosis of breast carcinoma. The authors evaluated the accuracy and
      clinical utility of VAB in a multicenter setting using a strict quality assurance
      protocol. METHODS: In the current study, VABs were performed successfully for
      2874 patients at 5 sites. Benign lesions were verified by follow-up. Surgery was
      recommended for malignant and borderline lesions. VAB was performed on patients
      with lesions rated as highly suspicious (6%), intermediate to suspicious (85%),
      or probably benign (9%). Fifty-eight percent of the lesions were < 10 mm and 70%
      had microcalcifications. RESULTS: The authors identified 7% of patients with
      invasive carcinomas, 15% with ductal carcinomas in situ (DCIS), 5% with atypical
      ductal hyperplasias (ADH), and 0.6% with lobular carcinomas in situ. The results
      of the VAB necessitated an upgrade of 24% of patients with ADH to DCIS or DCIS
      and invasive carcinoma. Twelve percent of patients with DCIS proved to have
      invasive carcinoma. Seventy-three percent of the patients had benign lesions.
      Only 1 false-negative result was encountered (negative predictive value, 99.95%).
      Minor side effects were reported to occur in 1.4% of patients and 0.1% of
      patients required a subsequent intervention. Scarring relevant for mammography
      was rare among patients (i.e., 0.3% of patients had relevant scarring).
      CONCLUSIONS: Quality-assured VAB was found to be highly reliable. VAB effectively
      identified patients with benign lesions and assisted therapeutic decisions. Most
      important, only a single case of malignancy was missed. A close interdisciplinary
      approach assured optimal results.

PMID- 14716758
TI  - Molecular markers for prognosis after isolated postmastectomy chest wall
      recurrence.
AB  - BACKGROUND: Local chest wall recurrence after mastectomy occurs in 10-20% of
      patients with operable breast carcinoma. The objective of the current study was
      to assess the prognostic value of molecular markers at the time of local
      recurrence and to compare these markers with clinical variables. METHODS: Between
      1975 and 1999, the authors treated 113 patients at their institution for
      postmastectomy chest wall recurrences with full-course external beam
      radiotherapy. Patients who presented primarily with lymph node recurrences or
      with simultaneous distant metastasis were excluded. Follow-up from the time of
      chest wall recurrence was 10.13 years. All clinical and pathologic data from the
      original diagnosis and from the time of chest wall recurrence were entered into a
      computerized database. Paraffin-embedded tumor specimens from the chest wall
      recurrences were available for 43 patients and were constructed into tissue
      microarrays for immunohistochemical staining of estrogen receptor, progesterone
      receptor (PR), p53, HER-2/neu, and cyclin D. RESULTS: Overall survival after
      chest wall recurrence for the entire cohort was 46% at 5 years and 28% at 10
      years. The distant metastasis-free survival rate was 49% at 5 years and 40% at 10
      years. Local-regional control of disease was achieved in 79% of patients at 10
      years. In multivariate analysis, significant factors for distant metastasis after
      local recurrence were time to recurrence (< 2 years from the original diagnosis
      to chest wall recurrence) and PR status (distant metastasis-free survival rate:
      84% [PR-positive] vs. 38% [PR-negative]; P = 0.007). The only significant factor
      for local-regional disease progression was HER-2/neu status. Patients with
      positive HER-2/neu status had a local-regional progression-free rate of 59%,
      compared with 92% for patients with negative HER-2/neu status. CONCLUSIONS: The
      prognosis for patients after local-regional recurrence of breast carcinoma is
      relatively poor. Longer time to local recurrence and positive PR status were
      associated with favorable distant metastasis-free rates and long-term survival.
      Positive HER-2/neu status was associated with poorer local-regional control of
      disease. Implications for systemic therapy and further studies are discussed.

PMID- 14716759
TI  - Frequency of HLA-C alleles in differentiated thyroid carcinoma in southeastern
      Spain.
AB  - BACKGROUND: The development of thyroid carcinoma may be influenced genetically
      and has been associated with certain HLA alleles. HLA-C alleles have not been
      studied in depth, because available serology techniques have not been very
      reliable in detecting them. However, the development of molecular biology
      provided an efficient and reliable technique for allele detection. The aims of
      the current study were to determine whether there is a significant association
      between any HLA-C allele and differentiated thyroid carcinoma and to establish
      the possible susceptibility or protection alleles related to these tumors.
      METHODS: HLA-C genotyping was performed in 63 patients undergoing surgery for
      differentiated thyroid carcinoma (57 patients with the papillary subtype and 6
      patients with the follicular subtype). A representative sample of 100 nonrelated
      healthy Caucasians was used as a control group from the same geographic area. The
      polymerase chain reaction-sequence-specific primer technique was used for HLA-C
      genotyping. The clinical variables analyzed were age, gender, family history of
      thyroid pathology, residence in areas of endemic goiter, asymptomatic status,
      presence of hyperthyroidism, compressive symptoms, presence of an intrathoracic
      thyroid component, histologic variables of the tumor, and evolution. The chi
      square test, the Mantel-Haenszel test, and the Bonferroni correction were used
      for the statistical analysis. RESULTS: In the control group, a significant
      correlation was observed between the lower frequency of the HLA-Cw7 allele and
      the development of differentiated thyroid carcinoma (P < 0.05). Analysis of the
      different clinical variables revealed a relation between HLA-C alleles and three
      clinical situations: cervical lymph node involvement with HLA-Cw7 and HLA-Cw2,
      vascular involvement with HLA-Cw7 and HLA-Cw1, and cervical carcinoma recurrence
      with HLA-Cw1. However, after application of the Bonferroni correction, only the
      association between HLA-Cw7 and lymphatic (P(c) = 0.0483) or vascular involvement
      (P(c) = 0.0324) persisted. CONCLUSIONS: The results revealed a relation between
      HLA-Cw7 and differentiated thyroid carcinoma. In future investigations, HLA-C
      typing may help to identify patients with a poor prognosis.

PMID- 14716760
TI  - Elevated perioperative serum vascular endothelial growth factor levels in
      patients with colon carcinoma.
AB  - BACKGROUND: To the authors' knowledge, little is known to date regarding the
      prognostic relevance of measuring serum levels of vascular endothelial growth
      factor (VEGF), a potent stimulator of angiogenesis, in patients with colon
      carcinoma who undergo surgery. METHODS: Preoperative and postoperative VEGF serum
      levels were determined by enzyme-linked immunoadsorbent assay in 81 patients with
      colon carcinoma who were undergoing surgery. Fifty healthy individuals served to
      define normal VEGF serum levels. RESULTS: Preoperative VEGF serum levels were
      significantly higher in the group of patients with colon carcinoma (mean, 504.1
      pg/mL +/- 223 pg/mL; range, 285-1390 pg/mL; 95% confidence interval [95%CI], 49
      pg/mL) compared with the control group (mean, 78.1 pg/mL +/- 22 pg/mL; range, 40
      110 pg/mL; 95%CI, 4.3 pg/mL; P < 0.001). Multiple regression analysis
      demonstrated a significant correlation (r) between preoperative VEGF serum levels
      and age (r = - 0.275; P = 0.013), Dukes stage (r = 0.488; P < 0.001), and
      carcinoembryonic antigen (CEA) levels (r = 0.285; P < 0.018). No significant
      correlation was found between preoperative VEGF serum levels and disease site,
      patient gender, tumor size, tumor grade, or performance status. Moreover,
      preoperative VEGF serum levels were significantly lower in patients who underwent
      curative surgery compared with patients who underwent noncurative surgery (443
      pg/mL +/- 117 pg/mL vs. 821 +/- 353 pg/mL, respectively; P < 0.0001). Logistic
      regression analysis selected preoperative VEGF and CEA serum levels as the only
      good prognostic indicators of curative and noncurative surgery (P < 0.001;
      relative risk, 2.98 and 2.03, respectively). Furthermore, VEGF serum levels
      dropped significantly after surgery, with a further downward trend until the 30th
      postoperative day (P < 0.001). Stepwise regression analysis selected preoperative
      VEGF serum level as the only variable associated significantly with the
      prediction of both disease-specific survival and disease-free survival (P =
      0.001). CONCLUSIONS: Preoperative serum VEGF levels may be useful for predicting
      outcome in patients with colon carcinoma who undergo surgery.

PMID- 14716762
TI  - Cigarette smoking and colorectal carcinoma mortality in a cohort with long-term
      follow-up.
AB  - BACKGROUND: Evidence suggests that colorectal carcinoma (CRC) may be a tobacco
      associated malignancy. METHODS: In the current study, the authors examined the
      association between cigarette smoking and CRC mortality in the Chicago Heart
      Association Detection Project in Industry study, a cohort of 39,299 men and women
      with an average of 26 years of follow-up. To assess whether the association was
      stronger in participants with a potentially long history of smoking, the authors
      also stratified the analysis using a baseline age > or = 50 years versus < 50
      years. RESULTS: Using multivariate Cox regression analysis, there was a
      marginally significant trend (P = 0.06) for men and women combined between
      smoking and CRC mortality. In the age-stratified analysis in the older
      participant group, there was no apparent association for men, women, or men and
      women combined. In the younger participant group, there appeared to be dose
      response relations for women and for men and women combined (P value for trend =
      0.008 and 0.03, respectively) between smoking and CRC mortality. The relative
      risk for women who smoked >20 cigarettes/day compared with never smokers was 2.49
      (95% confidence interval [95% CI], 0.87-7.12), and was 1.87 for men and women
      combined (95% CI, 1.08-3.22). CONCLUSIONS: The results of the current study
      support an association between cigarette smoking and CRC mortality, particularly
      in women age < 50 years.

PMID- 14716761
TI  - Randomized multicenter Phase II trial of two different schedules of irinotecan
      combined with capecitabine as first-line treatment in metastatic colorectal
      carcinoma.
AB  - BACKGROUND: The aim of the current randomized Phase II study was to investigate
      the efficacy and safety of capecitabine combined with irinotecan as first-line
      treatment in metastatic colorectal carcinoma (CRC). METHODS: A total of 140
      patients received capecitabine at a dose of 1250 mg/m(2) twice daily on Days 2-15
      and irinotecan at a dose of either 300 mg/m(2) on Day 1 (Arm A) or 150 mg/m(2) on
      Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment
      was continued using lower doses of capecitabine (1000 mg/m(2) twice daily) and
      irinotecan (Arm A: 240 mg/m(2); Arm B: 120 mg/m(2)) to improve the safety profile
      of the combinations. RESULTS: Efficacy was evaluable in 134 patients (68 in Arm
      A, 66 in Arm B). Objective responses were observed in 46% of the patients (8%
      complete response [CR]), including 47% in Arm A (9% CR; 38% partial response
      [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression-free survival was
      8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated
      with the higher doses, the most frequent Grade 3-4 adverse event was diarrhea
      (27%). The lower doses adopted in the subsequent 88 patients led to better
      diarrhea control, particularly in Arm A, and significant reductions in the
      incidence of all-grade hand-foot syndrome and abdominal pain. CONCLUSIONS: The
      capecitabine and irinotecan combination was a highly active first-line therapy in
      metastatic CRC. An acceptable safety profile was observed after dose reduction,
      particularly when irinotecan was administered on 1 day.

PMID- 14716763
TI  - Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive
      telomerase subunit hTERT.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein complex that protects the ends of
      chromosomes from degradation. Its catalytic subunit, hTERT, controls its
      activity. Prior data in prostate carcinoma cases indicated that
      immunohistochemical hTERT reactivity increases with tumor grade and may be absent
      in lower grade cases. The effect of complete androgen ablation (CAA) on tumor
      hTERT expression was uncertain. METHODS: hTERT immunostaining was performed on
      the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent
      CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing
      radical prostatectomy, and on their tumor tissue from radical prostatectomy. As
      controls, biopsy and prostatectomy samples from 30 untreated men were studied.
      Nuclear staining was evaluated by two observers, and the change in staining
      between biopsy and prostatectomy samples was evaluated using the Student t test
      in both groups. RESULTS: The percent of reactive tumor nuclei in treated men
      declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in
      untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's
      biopsy specimens was attributed to an increased proportion of higher (Gleason
      score > or = 7) grade tumors. The decline in hTERT immunostaining remained
      significant after normalizing it to that of the untreated group (P = 0.002). The
      original Gleason scores, corresponding declines in the percentage of reactive
      tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03);
      Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005)
      (from a mean 63% to 17%). CONCLUSIONS: CAA for prostate carcinoma can be
      considered an antitelomerase therapy. The steepest reduction in telomerase
      activity was noted in the highest grade tumors.

PMID- 14716764
TI  - Long-term outcomes after radical prostatectomy performed in a community-based
      health maintenance organization.
AB  - BACKGROUND: Radical prostatectomy is used widely for the treatment of patients
      with localized prostate carcinoma. No long-term analysis has been reported on a
      series of radical prostatectomies performed in a community-based health
      maintenance organization. METHODS: Charts and histologic slides were reviewed
      from 750 patients who underwent radical prostatectomy between 1970 and 1996 at a
      community-based health maintenance organization. The influences of a number of
      variables were analyzed for their impact on progression free survival (PFS) and
      overall survival (OS). RESULTS: With a median follow-up of 6.2 years among
      survivors, 137 patients (18%) had progressive disease, and 149 patients (20%)
      died from all causes. The median OS from the date of diagnosis was 15.7 years
      (95% confidence interval, 13.6-17.2), similar to the expected median survival of
      16.2 years. The median PFS from diagnosis was not reached, but 75% of patients
      were progression free > or = 10.6 years after undergoing prostatectomy. The
      prognostic factors included Gleason score, age at diagnosis, and T stage.
      Outcomes were comparable with reports of surgical series from university-based
      practices. CONCLUSIONS: The patient characteristics that had important, favorable
      correlation with survival included Gleason score < or = 6, T1 or T2 tumor status,
      and younger age at diagnosis. Lower prostate-specific antigen values at
      diagnosis, together with the former two parameters, also had a favorable
      correlation with PFS. Radical prostatectomy in a community-based health
      maintenance organization was followed by long-term PFS and OS comparable to
      outcomes reported from university-based practices. The impact of radical
      prostatectomy on survival remains to be demonstrated.

PMID- 14716765
TI  - News media coverage of human papillomavirus.
AB  - BACKGROUND: Now that human papillomavirus (HPV) DNA testing is being incorporated
      into cervical cancer screening programs, salient and accurate media information
      about HPV will be crucial to inform women's screening choices and to manage
      psychosocial responses to HPV DNA test results. METHODS: The authors conducted a
      content analysis of 111 news stories about HPV from the 10 most circulated
      newspapers and from 3 major television networks for the period from January 1995
      through July 2002. Stories were assessed for predominant theme (STD, cancer, or
      new tests); information about symptoms, transmission, prevention, and cancer
      causing properties of HPV; screening test descriptions; and recommended screening
      guidelines. RESULTS: Thirty-six percent of stories primarily were about new tests
      for HPV or cervical cancer, 30% of stories focused on cervical cancer or its link
      to HPV, and 27% of stories emphasized sexually transmitted diseases (STDs) or
      genital warts. Seventy-nine percent of stories mentioned that HPV is an STD, and
      50% of stories reported that HPV is very common. Twenty-six percent of stories
      reported that most women with HPV will not develop cervical carcinoma. Of 81
      stories that mentioned a screening test for HPV or cervical carcinoma, 38%
      reported the sensitivity of the test; 30% mentioned wrong, uncertain, or
      unnecessary test results; and 25% mentioned consequences of such results.
      CONCLUSIONS: Media coverage of HPV could better fulfill women's educational needs
      by including information about low-risk and high-risk types of HPV and their
      differing links to cervical cancer; describing HPV prevention, transmission, and
      symptoms; explaining the benefits and consequences of HPV testing; and outlining
      the latest screening guidelines in every story.

PMID- 14716766
TI  - Women's desired information about human papillomavirus.
AB  - BACKGROUND: As human papillomavirus (HPV) DNA testing is incorporated into
      cervical carcinoma screening programs, educational messages must be developed to
      inform women's screening choices and manage psychosocial responses to HPV DNA
      test results. However, little is known about women's questions and concerns about
      HPV or their attitudes toward HPV testing. METHODS: Eight focus groups with 48
      ethnically diverse, low-income women were conducted at community centers, family
      planning and primary care clinics, and substance abuse rehabilitation facilities
      in Massachusetts. RESULTS: The participants' comments and questions about HPV
      revealed five major themes. First, most women overestimated the likelihood that
      women with HPV would develop cancer. Second, women struggled to balance the
      anxiety of knowing that HPV infection causes cervical carcinoma with the
      information that HPV infection often regresses without treatment. Third, many
      women were confused that Papanicolaou smear results could be normal when HPV
      infection is present. Fourth, women preferred to receive a personalized risk
      profile to assess their own likelihood of contracting HPV infection and cervical
      carcinoma. Fifth, younger women focused on the sexual transmission of HPV
      infection, rather than on its potential to cause cancer. CONCLUSIONS: Effective
      HPV education must include information about transmission, prevention, treatment,
      and cervical carcinoma risk; tailor messages to describe HPV susceptibility
      according to age and risk profile; present clarification regarding HPV strains
      and their consequences; offer explanations of different types of tests and their
      results; and provide a balance between accurate discussion of cancer risk and
      reassurance that following recommended screening practices will reduce risk to
      negligible levels.

PMID- 14716767
TI  - A Phase II trial of aprinocarsen, an antisense oligonucleotide inhibitor of
      protein kinase C alpha, administered as a 21-day infusion to patients with
      advanced ovarian carcinoma.
AB  - BACKGROUND: It has been postulated that protein kinase C alpha (PKC-alpha) plays
      a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 20
      base antisense oligonucleotide, has shown ability to inhibit PKC-alpha protein
      expression and inhibit tumor growth in human xenograft models. In a previous
      Phase I trial, the authors demonstrated the safety and some evidence of activity
      in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous,
      intravenous infusion. METHODS: In this Phase II trial, 36 patients with advanced
      ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day
      delivered as a 21-day, continuous, intravenous infusion. The primary objective
      was to determine the antitumor response, and the secondary objectives were to
      evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS:
      Between September 1997 and December 1999, 36 patients (median age, 58 years) were
      enrolled in this trial. Patients were stratified into 2 groups: a platinum
      sensitive group (n = 12 patients) and a platinum-resistant group (n = 24
      patients). All 36 patients were evaluable for toxicity, and 27 patients were
      fully assessable for antitumor response after 2 cycles of therapy. All patients
      had received prior treatments. No objective responses were noted in the platinum
      sensitive group. In the platinum-resistant group, 1 patient had some evidence of
      antitumor activity indicated by a decrease in serum CA 125 and stable disease on
      imaging studies for 8 months. No changes were noted in overall patient ratings
      for any of the five QOL domains. CONCLUSIONS: When it was administered as a
      single agent, aprinocarsen did not have significant clinical activity in patients
      with advanced ovarian carcinoma. Further study may be warranted in combination
      with platinum-based regimens.

PMID- 14716768
TI  - Human papillomavirus-31-related types predict better survival in cervical
      carcinoma.
AB  - BACKGROUND: The aim of the current study was to explore the clinical implications
      and prognostic value of human papillomavirus (HPV) genotype in cervical
      carcinomas. METHODS: A total of 152 patients diagnosed with International
      Federation of Gynecology and Obstetrics Stage I-IV cervical carcinoma were
      studied between 1992-1999. HPV DNA status was assessed from paraffin-embedded,
      formaldehyde-fixed cervical carcinoma specimens by polymerase chain reaction
      based methods using E7 type-specific and L1 modified general primers (MY11/GP6+
      and GP5+/GP6+). The authors divided the patients into four groups: HPV-16
      related, HPV-18-related, HPV-31-related, and HPV-58-related types. The relations
      with clinicopathologic data and overall survival were evaluated. RESULTS: HPV DNA
      was detected in 98% of the tumor specimens and 28.9% of the tumor specimens
      contained multiple HPV types. The HPV-16-related types were detected more often
      in squamous cell carcinomas, whereas the HPV-18-related types were more prevalent
      in adenocarcinomas and adenosquamous carcinomas. In addition, Stage I-II diseases
      were found more frequently in the HPV-16-related group than in the other groups
      (P = 0.001). Otherwise, no significant correlation between the HPV genotype and
      other clinicopathologic parameters was found. After a median follow-up of 64.5
      months, the 5-year survival rate was 92% in the HPV-31-related group compared
      with 70% in the HPV-16-related group, 69% in the HPV-18-related group, and 36% in
      the HPV-58-related group. The survival rates statistically differed among the
      four groups by log-rank test (P = 0.02). However, the presence of multiple HPV
      types was not associated with prognosis. After stratifying for clinical stage,
      multivariate analysis demonstrated that HPV genotype was an independent
      prognostic factor. Compared with the HPV-16-related group, the long-term
      mortality rate was 73 % lower in the HPV-31-related group (relative risk, 0.27;
      95% confidence interval, 0.09-0.76; P = 0.013). CONCLUSIONS: The presence of HPV
      31-related types was an independent predictor of better survival in patients with
      cervical carcinoma. Therefore, HPV genotyping of cervical carcinomas may have
      profound implications for future patient management.

PMID- 14716769
TI  - Comparative genomic hybridization in primary sinonasal adenocarcinomas.
AB  - BACKGROUND: Little is known about the genetic alterations that occur in sinonasal
      adenocarcinomas. The goal of the current study was to detect recurrent
      chromosomal gains and losses in a series of 21 primary sinonasal adenocarcinomas
      using comparative genomic hybridization (CGH). METHODS: The authors examined
      ethmoid sinus adenocarcinoma samples from 21 patients. All 21 adenocarcinomas
      were associated with work-related exposure to wood dust. CGH was used to detect
      chromosomal abnormalities, and the results of CGH analysis were evaluated for
      correlations with clinicopathologic characteristics. RESULTS: Chromosomal gains
      and losses were detected in all 21 adenocarcinomas. Gains were detected at high
      frequencies at 7q11-21 (n = 15 [71%]), 18p11 (n = 14 [66%]), 8q11-22 (n = 13
      [62%]), 5p11-13 (n = 12 [57%]), 12q11-13 and 19p (n = 11 [52%]), 20q (n = 10
      [47%]), X and 5p (n = 9 [43%]), and 3q26-27 (n = 8 [38%]); and losses were
      detected at 8p22-23 (n = 18 [86%]), 18q22-23 (n = 17 [80%]), 17p13 (n = 12
      [57%]), and 5q31-qter (n = 11 [52%]). Aside from low-level gains, 43 high-level
      amplifications were observed in the current series of 21 tumors, most commonly at
      Xq13 (n = 7 [33%]). CONCLUSIONS: CGH revealed that ethmoid sinus adenocarcinomas
      carry a large number of chromosomal losses and gains, including high-level
      amplifications. To the authors' knowledge, the current study represents the first
      attempt to investigate sinonasal adenocarcinomas on a genetic level by using CGH.
      The pattern of chromosomal abnormalities in these tumors was different from the
      pattern in other tumors within the same anatomic region (e.g., squamous cell
      carcinomas and salivary gland tumors); this finding may be explained by
      differences in etiology. Nonetheless, sinonasal adenocarcinomas appear to be
      genetically similar to adenocarcinomas of the stomach and colon, which also have
      an etiology that differs from that of sinonasal adenocarcinomas. Further study is
      necessary to better understand the molecular genetic basis underlying the
      development of sinonasal adenocarcinomas. In the near future, this type of
      understanding may present new possibilities for prevention and treatment of
      malignant disease.

PMID- 14716770
TI  - Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of
      an M.D. Anderson Cancer Center series.
AB  - BACKGROUND: The goal of the current study was to assess the toxicity, safety, and
      efficacy of pentostatin in patients with T-cell lymphoid malignancies. METHODS:
      Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and
      failure to respond to previous therapy or an expected complete response rate to
      conventional therapy of < 20%. Pentostatin was administered at an initial dose of
      3.75 or 5.0 mg/m(2) by intravenous bolus daily over a consecutive 3-day period
      every 3 weeks. RESULTS: Forty-two of 44 patients enrolled in the study were
      evaluable. The median age of the patients was 62 years (range, 38-86 years).
      Patients received a median of 3 previous therapies (range, 0-10 previous
      therapies). Of these patients, 32 (76%) had mycosis fungoides/Sezary syndrome and
      10 patients (24%) had other T-cell leukemias or lymphomas. The overall response
      rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17
      patients [40.5%]). Durable responses were observed mainly in patients with Sezary
      syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving
      patients was 20 months (range, 1-83+ months). The median duration of response was
      4.3 months (range, 1-61 months). The most common toxicities were neutropenia,
      nausea, and CD4 suppression. A transient early "flare" of disease was observed in
      some responders. CONCLUSIONS: At these doses, pentostatin was reasonably well
      tolerated and is an effective drug for the treatment of T-cell lymphomas.

PMID- 14716771
TI  - Long-term follow-up of patients with intermediate or high-grade non-Hodgkin
      lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine,
      and prednisone.
AB  - BACKGROUND: Doxorubicin cardiotoxicity is one of the most serious side effects of
      the cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy,
      regimen, especially among elderly patients. In the CEOP regimen, epirubicin was
      substituted for doxorubicin to reduce cardiotoxicity. METHODS: Between March 1984
      and September 1998, 186 previously untreated patients with a histologically
      confirmed diagnosis of intermediate- or high-grade non-Hodgkin lymphoma according
      to the Working Formulation were treated with CEOP (cyclophosphamide, 750 mg/m(2),
      epirubicin, 75 mg/m(2), vincristine, 1.4 mg/m(2); and prednisone, 60 mg per day
      orally on Days 1-5). Of 186 patients, 85 (45.7%) had Stage IV disease, and 60
      (32.3%) had an International Prognostic Index score > 2. Comorbidity was present
      in 36 patients (19.3%). RESULTS: Complete remission (CR) was achieved in 119
      patients (64.3%), and partial remission was achieved in 30 patients (16.2%).
      Among the patients who achieved a CR, 95 (79.8%) were still disease free at a
      median follow-up time of 86.9 months (range, 14-200 months). The remaining 24
      patients experienced disease recurrence, at a median follow-up time of 19 months
      (range, 3-101 months). The relative dose intensities were 0.69, 0.89, and 0.80
      for vincristine, epirubicin, and cyclophosphamide, respectively. Two patients
      died of toxicity due to infection. Two patients, 59 and 73 years old,
      respectively, experienced arrhythmia. Another patient, age 64 years, who had a
      myocardial infarction 10 years earlier, had angina. One patient with hypertension
      experienced cardiac failure. No patients died of cardiac toxicity. CONCLUSION:
      Long-term follow-up confirmed that CEOP is an effective and well-tolerated
      chemotherapy regimen for intermediate- and high-grade lymphoma. The results were
      promising, especially among elderly patients.

PMID- 14716772
TI  - Expression of matrix metalloproteinase 9 is a prognostic factor in patients with
      non-Hodgkin lymphoma.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of tumors
      that vary with regard to their biologic aggressiveness and clinical course. In in
      vitro studies, matrix metalloproteinase 9 (MMP9) was reportedly expressed by
      human NHL cells and elevated levels of MMP9 have been observed in a subset of
      patients with high-grade NHL. METHODS: The expression of MMP2 and MMP9 was
      evaluated in 158 patients with NHL and the relation between the expression of
      these proteins and clinicopathologic factors was analyzed. All but 1 patient had
      received radiation therapy and 92 patients also were treated with intensive
      combination chemotherapy. RESULTS: Nearly all the patients with extranodal
      natural killer NK/T-cell lymphoma nasal type and anaplastic large cell lymphoma,
      T-cell/null cell type expressed MMP9. In contrast, only a small fraction of the
      patients with mucosa-associated lymphoid tissue (MALT) lymphomas and follicular
      lymphomas expressed MMP9. Approximately 50% of the diffuse large B-cell lymphoma
      (DLBCL) cases expressed MMP9. The expression of MMP2 was noted in some of the
      patients with DLBCL and nasal NK/T-cell lymphoma. The overall survival rates of
      patients who expressed MMP9 were significantly lower than that of those who did
      not. Such a correlation was not demonstrated in MMP2 expression. When MMP9
      expression was analyzed in DLBLC patients, the overall survival rates of patients
      who expressed MMP9 were significantly lower than those who did not express MMP9.
      Chemotherapy was associated with better overall survival in DLBCL patients who
      expressed MMP9. Overall survival rates of T-cell/NK-cell lymphoma patients who
      expressed MMP9 appeared to be lower than that in those who did not express MMP9.
      However, chemotherapy was not found to improve overall survival in patients who
      expressed MMP9. CONCLUSIONS: MMP9 expression was observed in patients with
      aggressive NHL and was characterized by poor overall survival.

PMID- 14716773
TI  - Treatment outcome and pattern of failure in 77 patients with sinonasal natural
      killer/T-cell or T-cell lymphoma.
AB  - BACKGROUND: Sinonasal natural killer (NK)/T-cell or T-cell lymphoma behaves quite
      differently from other lymphomas. The objective of this study was to investigate
      clinical features, treatment outcomes, and failure patterns in patients with this
      type of sinonasal lymphoma. METHODS: From September, 1977 to December, 2000, 77
      patients with sinonasal NK/T-cell lymphoma or T-cell lymphoma who had received
      radiotherapy (R/T), chemotherapy (C/T), or both (R/T and C/T) were evaluated
      retrospectively. RESULTS: Fifty-six patients (73%) had locoregional disease only,
      and 21 patients (27%) had systemic involvement. Forty-four patients (57%)
      achieved a complete remission (CR). The 5-year overall survival rate was 36%
      (median follow-up, 89 months). Achievement of CR was the only prognostic factor
      for survival in multivariate analysis. Among patients with locoregional disease,
      the CR rate was 63%, and the 5-year overall survival rate was 42%. Combined R/T
      and C/T or R/T alone resulted in better survival compared with C/T alone (5-year
      survival rates, 59%, 50%, and 15%, respectively; P = 0.01). Incidences of
      locoregional and systemic failure were 43% and 30%, respectively. Outcome was
      dismal for patients with systemic disease, with a CR rate of 43% and a 5-year
      survival rate of 25%. Only 2 of 21 patients had sustained remissions. The
      locoregional and systemic failure rates were 57% and 71%, respectively.
      CONCLUSIONS: Treatment outcomes were unsatisfactory for patients with
      locoregional and systemic sinonasal NK/T-cell or T-cell lymphoma. R/T could not
      control locoregional disease satisfactorily, and C/T was unable to eradicate
      systemic disease in many patients. High-dose therapy may be worth studying in
      these patients. New treatments should be investigated to increase remission
      rates, prevent failure, and improve survival.

PMID- 14716774
TI  - Prospective randomized controlled study of interferon-alpha in preventing
      hepatocellular carcinoma recurrence after medical ablation therapy for primary
      tumors.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after ablation therapy for
      primary tumors is common. METHODS: To evaluate the effectiveness of interferon
      alpha (IFN-alpha) in preventing HCC recurrence, 30 eligible patients were
      randomized into three groups: 11 patients treated with three mega units (MU) of
      IFN-alpha three times weekly for 24 months (IFN-alpha-continuous group), 9
      patients treated with 3 MU of IFN-alpha daily for 10 days every month for 6
      months followed by 3 MU of IFN-alpha daily for 10 days every 3 months for a
      further 18 months (IFN-alpha-intermittent group), and 10 patients who received no
      IFN-alpha therapy (control group). The three groups were comparable in terms of
      etiology, demographics, and laboratory data at entry and HCC characteristics.
      RESULTS: After a median follow-up of 27 months (range 4-53 months), 9 patients
      (90%) in the control group and 9 patients (45%) in 2 treatment groups (6 patients
      in the IFN-alpha-continuous group and 3 patients in the IFN-alpha-intermittent
      group) developed an HCC recurrence (P = 0.021). Cumulative HCC recurrence rates
      in the IFN-alpha-intermittent, IFN-alpha-continuous, and control groups were
      22.2%, 27.3%, and 40% at the end of 1 year and 33.3%, 54.6%, and 90% at the end
      of 4 years (P = 0.0375), respectively (control vs. IFN-alpha-intermittent group,
      P = 0.0123; vs. IFN-alpha-continuous group, P = 0.0822). If both IFN-alpha groups
      were combined, the cumulative HCC recurrence rate of the patients treated with
      IFN-alpha and the control group was 25% and 40% at the end of 1 year and 47% and
      90% at the end of 4 years, respectively (P = 0.0135). CONCLUSIONS: The data
      suggested that IFN-alpha therapy may reduce HCC recurrence after medical ablation
      therapy for primary tumors.

PMID- 14716775
TI  - Elective radiotherapy provides regional control for patients with cutaneous
      melanoma of the head and neck.
AB  - BACKGROUND: In the current study, the authors assessed the efficacy of elective
      radiotherapy in providing regional (lymph node) control in patients with
      cutaneous melanoma of the head and neck who were at high risk for lymph node
      involvement. Toxicity was also assessed. METHODS: From 1983 to 1998, 157 patients
      with Stage I or II cutaneous melanoma of the head and neck received elective
      regional radiotherapy after wide local excision of the primary lesion. None of
      the patients had received sentinel lymph node biopsy or dissection of the lymph
      nodes. Their medical records were reviewed retrospectively and analyzed for
      outcome. RESULTS: The median follow-up for the current review was 68 months
      (range, 7-185 months). The disease recurred locally in 9 patients, in the neck
      lymph nodes in 15 patients, and distantly in 57 patients. The actuarial regional
      control rate was 89% at both 5 years and 10 years. The actuarial disease-specific
      survival and distant metastasis-free survival rates were 68% and 63%,
      respectively, at 5 years and 58% and 49%, respectively, at 10 years. Breslow
      thickness was a significant determinant of disease-specific survival and distant
      metastasis-free survival rates. At 10 years, 6% of patients had developed a
      symptomatic treatment-related complication. There were no treatment-related
      deaths. CONCLUSIONS: The results of the current study confirmed the efficacy and
      safety of elective regional radiotherapy for patients with cutaneous head and
      neck melanoma predicted to have a high rate of lymph node involvement. Elective
      irradiation was a viable alternative to elective lymph node dissection. It may
      also serve as an alternative to sentinel lymph node biopsy, particularly for
      patients for whom dissection and systemic therapy are not therapeutic options.

PMID- 14716776
TI  - Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive
      clinical behavior.
AB  - BACKGROUND: Among cases of undifferentiated and poorly differentiated tumors in
      the neuroblastoma (Schwannian stroma-poor) category, the authors histologically
      identified a group of rare tumors, known as large cell neuroblastomas (LCNs),
      that are composed of large cells with sharply outlined nuclear membranes and 1-4
      prominent nucleoli. METHODS: Histologic and immunohistochemical features of LCN
      were characterized. Morphologic characteristics, clinical features, and MYCN
      status were compared between LCNs and conventional neuroblastomas documented in
      the files of two European centers (the Sir James Spence Institute of Child
      Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne,
      United Kingdom, and the Medical and Health Sciences Center, University of Pecs,
      Pecs, Hungary). RESULTS: Of 92 peripheral neuroblastic tumors (pNTs; including
      neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and
      ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs
      were classified as having unfavorable histology (UH) according to the
      International Neuroblastoma Pathology Classification. The LCNs were composed of
      monomorphous undifferentiated neuroblasts and shared certain histologic features,
      such as a high incidence of high mitosis-karyorrhexis index and a low incidence
      of calcification, with other neuroblastomas in the conventional UH (c-UH) group.
      These features were significantly different from those of neuroblastomas in the
      conventional favorable histology (c-FH) group. On immunohistochemical analysis,
      LCN tumor cells were positive for neuron-specific enolase (5 of 5 cases), protein
      gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine
      hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for
      CD99. Patients with LCN and patients with c-UH disease had similar clinical
      features (diagnosis at age > 1 year, often with distant metastasis). The clinical
      features of these patients also were significantly different from those of
      patients with c-FH disease. Further analysis demonstrated that the LCN group was
      significantly different from both the c-UH and c-FH groups with respect to MYCN
      status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P =
      0.023) and survival rate (4-year expected survival, 0% vs. 71% vs. 17%,
      respectively; P < 0.01). CONCLUSIONS: Because of its unique clinicopathologic
      features, the authors propose that LCN be recognized as a distinct entity within
      the undifferentiated and poorly differentiated subtypes of the neuroblastoma
      category.

PMID- 14716777
TI  - Phase II study of alpha-tocopherol in improving the cognitive function of
      patients with temporal lobe radionecrosis.
AB  - BACKGROUND: Radiotherapy is an important treatment modality for brain tumors and
      is the standard radical treatment for nasopharyngeal carcinoma (NPC). However,
      the treatment is not free of side effects, and one possible neurologic sequela is
      the occurrence of temporal lobe radionecrosis (TLN) associated with cognitive
      dysfunction. Currently, there is no effective intervention to improve patients'
      cognitive performance. METHODS: Twenty-nine patients with TLN after radiotherapy
      for NPC were recruited on a voluntary basis. Among them, 19 patients (15 males
      and 4 females) received a megadose of alpha-tocopherol (vitamin E) (2000
      international units per day) for 1 year, whereas the other 10 (5 males and 5
      females) served as control patients. Their cognitive function (i.e., global
      cognitive ability, attention, memory, language, and executive function) was
      evaluated by a battery of neuropsychological tests before and after treatment.
      RESULTS: Significant improvement in global cognitive ability (P = 0.035) and
      memory (verbal: P = 0.036; visual: P = 0.007) occurred among patients in the
      treatment group after a 1-year medication period. In addition, the executive
      function of the treatment group improved significantly (P = 0.04). No difference
      was found between the two groups with respect to attention or language.
      CONCLUSIONS: The current investigation was a preliminary study on the effect of
      alpha-tocopherol on the cognitive function of patients with TLN after
      radiotherapy for NPC. In view of the absence of effective treatment for patients
      with cerebral radionecrosis, alpha-tocopherol has the potential to be a
      complementary intervention for patients with cognitive dysfunction due to TLN.

PMID- 14716778
TI  - Stereotaxic implantation of 5-fluorouracil-releasing microspheres in malignant
      glioma.
AB  - BACKGROUND: The authors developed a new method of drug delivery into the brain
      using implantable, biodegradable microspheres. The strategy was evaluated
      initially to provide localized and sustained delivery of the radiosensitizer 5
      fluorouracil (5-FU) after patients underwent surgical resection of malignant
      glioma. In this study, the microspheres were implanted by stereotaxy into deeply
      situated and inoperable brain tumors. METHODS: Ten patients with newly diagnosed,
      inoperable, malignant gliomas were included in the study, and 1 dose of 5-FU was
      studied (132 mg). After histologic confirmation, a suspension of poly(D-L lactide
      co-glycolide) 5-FU-loaded microspheres was implanted by stereotaxy into the tumor
      in one or several trajectories with one to seven deposits per trajectory.
      External beam radiation (59.4 grays) was started before postoperative Day 7.
      Patients were followed by clinical examination, computed tomography scanning,
      magnetic resonance imaging, and 5-FU assays in blood and cerebrospinal fluid
      (CSF). RESULTS: The number of trajectories was adapted to the size and shape of
      the tumor. Microsphere implantation was tolerated well, except in four patients
      who received a single trajectory and experienced a transitory worsening of
      preexisting neurologic symptoms. There were no episodes of edema or hematologic
      complications. 5-FU was detected in CSF and blood in some patients at very low
      concentrations. The median overall survival was 40 weeks, with 2 patients who had
      longer survival (71 weeks and 89 weeks, respectively). CONCLUSIONS: In this
      study, the authors demonstrated that biodegradable microspheres could be
      implanted by stereotaxy and were efficient systems for drug delivery into brain
      tumors. This method may have future applications in the treatment of patients
      other malignancies.

PMID- 14716779
TI  - Genetic polymorphisms in the Hmong population: implications for cancer etiology
      and survival.
AB  - BACKGROUND: The Hmong, an isolated, agrarian people from southern China, migrated
      to the mountainous regions of what are today Vietnam, Cambodia, and Laos.
      Minnesota has the second largest Hmong population in the United States. The
      authors compared frequencies of common genetic polymorphisms believed to
      influence risk of malignancy to determine whether frequencies in the Hmong are
      different from those in other Asian populations and in white Minnesotans.
      METHODS: Genotyping for glutathione S-transferase micro1 (GSTM1), glutathione S
      transferase theta1 (GSTT1), myeloperoxidase (MPO) (C(-)463T), nicotinamide
      adenine dinucleotide phosphate:quinone oxidoreductase (NQO1) (C609T), 5,10
      methylenetetrahydrofolate reductase (MTHFR) (C677T), MTHFR (A1298C), methionine
      synthase reductase (MTRR) (A66G), X-ray repair cross complementing 1 (XRCC1) 194
      (Arg194Trp), XRCC1 280 (Arg280His), and XRCC1 399 (Arg399Gln) alleles was
      performed by TaqMan analysis using DNA isolated from newborn heel-stick spots
      provided by the Minnesota Department of Health. RESULTS: The Hmong had
      significantly higher frequencies of the NQO1 T allele and the XRCC1 Trp
      polymorphism (Arg194Trp) and had significantly lower frequencies of the G allele
      in MTRR (A66G) and the T allele in MTHFR (C677T) compared with white Minnesotans.
      The Hmong also were significantly more likely to lack the GSTM1 and GSTT1 genes
      compared with whites (82% vs. 54% and 61% vs. 18%, respectively). Genotype
      frequencies were similar for MTHFR (A1298C), MPO (C(-)463T), and XRCC1
      (Arg280His, Arg399Gln). Genotype frequencies at these loci also were compared
      with those reported for other Asian populations and showed notable differences
      between the Hmong and Chinese/Taiwanese, Korean, and Japanese populations.
      CONCLUSIONS: The genetic differences identified have implications for both cancer
      etiology and prognosis in this unique population.

PMID- 14716780
TI  - Racial disparities in the use of and indications for colorectal procedures in
      Medicare beneficiaries.
AB  - BACKGROUND: African Americans are diagnosed more frequently with colorectal
      carcinoma at a later stage compared with Caucasians. One potential reason for the
      disparity is a lower rate of screening examinations. METHODS: Using Outpatient
      and Physician-Supplier claims for all Medicare beneficiaries age > or = 65 years
      in 1999, indications for fecal occult blood testing (FOBT), sigmoidoscopy,
      colonoscopy, and barium enema were divided into diagnostic, surveillance, or
      screening categories. Annualized rates were calculated based on the number of
      eligible fee-for-service months. RESULTS: Rates of FOBT (18.24% vs. 11.86%; P <
      0.001) and sigmoidoscopy (3.07% vs. 2.17%; P < 0.001) were higher in Caucasians
      compared with African Americans, whereas rates of barium enema were higher in
      African Americans (2.26% vs. 1.88%; P < 0.001). Colonoscopy use was more frequent
      among men only in Caucasians compared with African-Americans (8.00% vs. 6.97%; P
      < 0.001). For FOBT, sigmoidoscopy, and colonoscopy, the racial differences in
      procedures performed for diagnostic purposes were of smaller magnitude than for
      screening; and, for colonoscopy, the use of diagnostic procedures actually was
      higher for African Americans. CONCLUSIONS: Racial disparities exist not only in
      the use of colorectal procedures but also in the indications for such testing,
      with African Americans less likely to undergo screening tests. The differences
      are consistent with delay in diagnosis until symptoms or signs develop and may
      contribute to disparities in cancer mortality.

PMID- 14716781
TI  - Quality of life as a survival predictor for patients with advanced head and neck
      carcinoma treated with radiotherapy.
AB  - BACKGROUND: Accumulating reports suggest that quality of life (QoL) may predict
      survival in patients with malignant disease. In the current study, the authors
      investigated if baseline QoL and changes in QoL during treatment were prognostic
      for patients with advanced head and neck squamous cell carcinoma (HNSCC) treated
      with radiotherapy. METHODS: The authors studied 102 consecutive new patients with
      HNSCC treated with primary radiotherapy. The Taiwan Chinese versions of the
      European Organization for the Research and Treatment of Cancer Core Quality of
      Life Questionnaire (EORTC QLQ-C30) and Head and Neck Quality of Life
      Questionnaire (EORTC QLQ-H&N35) were completed before and during radiotherapy.
      The Cox proportional hazards models were used to analyze the impact of clinical
      and QoL variables on survival. RESULTS: Clinical variables that were significant
      survival predictors included American Joint Committee on Cancer (AJCC) stage, N
      status, and Karnofsky performance status (KPS) after multivariate analysis. After
      introducing the QoL variables, baseline fatigue scale and N status emerged as the
      most significant survival predictors, whereas KPS lost its significance. Changes
      in the QoL scales during radiotherapy were not significantly correlated with
      survival. An increase in the baseline fatigue score of 10 points corresponded to
      a 17% reduction in the likelihood of survival (95% confidence interval: 8-27%).
      Significant correlations between baseline fatigue scale and KPS, comorbidity,
      hemoglobin level, AJCC stage, T status, and most QoL scales also were observed.
      CONCLUSIONS: The data support the correlation of patient reported QoL scales with
      survival. Pretreatment fatigue level was a significant survival predictor for
      patients with advanced HNSCC treated with radiotherapy.

PMID- 14716782
TI  - Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring
      less than 2.1-mm thick).

PMID- 14716783
TI  - Identification of germline 185delAG BRCA1 mutations in non-Jewish Americans of
      Spanish ancestry from the San Luis Valley, Colorado.

PMID- 14716785
TI  - BJS--looking to the future.

PMID- 14716786
TI  - From Correspondenzblatt to BJS - a century of Swiss surgical publishing.

PMID- 14716787
TI  - Oesophagectomy - lessons from China.

PMID- 14716788
TI  - Trials in surgery.
AB  - BACKGROUND: Trials in surgery pose some special problems. This paper examines
      these with reference to 10 years of methodological research sponsored by the UK
      National Health Service Research and Development programme. METHODS: Solutions to
      common problems encountered in surgical studies were considered, such as issues
      of blinding, dependence of results on technical skill and continued evolution of
      technology. RESULTS: Numerous methodological developments are described,
      including the tracker trial concept in which trial design can be adapted to take
      account of technical developments and interim results. The governance of trials,
      solutions to ethical conundra and the rising importance of databases are also
      discussed. CONCLUSION: Like surgery itself, the methodological toolkit for
      evaluation of surgical procedures continues to evolve. The rules of statistical
      and scientific probity provide plenty of scope for imaginative design solutions
      for surgical trials.

PMID- 14716789
TI  - Systematic review of survival after acute mesenteric ischaemia according to
      disease aetiology.
AB  - BACKGROUND: Differentiation of acute mesenteric ischaemia on the basis of
      aetiology is of great importance because of variation in disease progression,
      response to treatment and outcome. The aim of this study was to analyse the
      published data on survival following acute mesenteric ischaemia over the past
      four decades in relation to disease aetiology and mode of treatment. METHOD: A
      systematic review of the available literature from 1966 to 2002 was performed.
      RESULTS: Quantitative analysis of data derived from 45 observational studies
      containing 3692 patients with acute mesenteric ischaemia showed that the
      prognosis after acute mesenteric venous thrombosis is better than that following
      acute arterial mesenteric ischaemia; the prognosis after mesenteric arterial
      embolism is better than that after arterial thrombosis or non-occlusive
      ischaemia; the mortality rate following surgical treatment of arterial embolism
      and venous thrombosis (54.1 and 32.1 per cent respectively) is less than that
      after surgery for arterial thrombosis and non-occlusive ischaemia (77.4 and 72.7
      per cent respectively); and the overall survival after acute mesenteric ischaemia
      has improved over the past four decades. CONCLUSION: There are large differences
      in prognosis after acute mesenteric ischaemia depending on aetiology. Surgical
      treatment of arterial embolism has improved outcome whereas the mortality rate
      following surgery for arterial thrombosis and non-occlusive ischaemia remains
      poor.

PMID- 14716790
TI  - Meta-analysis of the clinical and laboratory diagnosis of appendicitis.
AB  - BACKGROUND: The importance of specific elements in the clinical diagnosis of
      appendicitis is controversial. This review analyses the diagnostic value of
      elements of disease history, clinical findings and laboratory test results in
      suspected appendicitis. METHODS: A systematic Medline search was made of all
      published studies on the clinical and laboratory diagnosis of appendicitis in
      patients admitted to hospital with suspected disease. Meta-analyses of receiver
      operator characteristic (ROC) areas, and positive and negative likelihood ratios,
      of 28 diagnostic variables described in 24 studies are presented. RESULTS:
      Inflammatory response variables (granulocyte count, proportion of
      polymorphonuclear blood cells, white blood cell count and C-reactive protein
      concentration), descriptors of peritoneal irritation (rebound and percussion
      tenderness, guarding and rigidity) and migration of pain were the strongest
      discriminators, with ROC areas of 0.78 to 0.68. The discriminatory power of the
      inflammatory variables was particularly strong for perforated appendicitis, with
      ROC areas of 0.85 to 0.87. Appendicitis was likely when two or more inflammatory
      variables were increased and unlikely when all were normal. CONCLUSION: Although
      all clinical and laboratory variables are weak discriminators individually, they
      achieve a high discriminatory power when combined. Laboratory examination of the
      inflammatory response, clinical descriptors of peritoneal irritation, and a
      history of migration of pain yield the most important diagnostic information and
      should be included in any diagnostic assessment.

PMID- 14716791
TI  - Randomized clinical trial comparing level II and level III axillary node
      dissection in addition to mastectomy for breast cancer.
AB  - BACKGROUND: In addition to mastectomy, level II and level III axillary node
      dissection procedures are performed widely in Japan. A randomized clinical trial
      was performed to determine which procedure was more effective. METHODS: One group
      of women had resection of the pectoralis minor muscle and dissection of level I,
      II and III axillary lymph nodes (level III dissection). In a second group, the
      pectoralis minor muscle was left intact and level III axillary lymph node
      dissection was not performed (level II dissection). A total of 1209 women with
      stage II breast cancer were enrolled in the study and randomly assigned to one of
      the two groups. RESULTS: The 10-year cumulative survival rate was 86.6 per cent
      after level II and 85.7 per cent after level III axillary dissection (hazard
      ratio (HR) 1.02; P = 0.931, log rank test). The 10-year disease-free survival
      rate was 73.3 and 77.8 per cent respectively (HR 0.94, P = 0.666). Overall
      survival and disease-free survival rates in the two groups were similar after
      both procedures. The duration of surgery was significantly shorter (P < 0.001)
      and blood loss was significantly less (P = 0.001) after level II dissection. In a
      survey of patients' symptoms on follow-up, no significant differences were found
      between the two procedures. CONCLUSION: The addition of pectoralis minor muscle
      resection and level III axillary lymph node dissection to mastectomy for stage II
      breast cancer did not improve overall or disease-free survival rates.

PMID- 14716792
TI  - Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal
      hernia repair.
AB  - BACKGROUND: Almost half the patients who undergo hernia repair with mesh report a
      feeling of stiffness and a foreign body in the groin. This study evaluated
      whether patients noticed any difference between lightweight and standard
      polypropylene mesh for the repair of inguinal hernia. METHODS: Patients scheduled
      for elective repair of unilateral or bilateral, primary or recurrent inguinal
      hernia by the Lichtenstein technique were randomized to receive either a
      conventional densely woven polypropylene mesh (100-110 g/m(2)) or a lightweight
      composite multifilament mesh (polypropylene 27-30 g/m(2)). Quality of life was
      assessed using Short Form 36 before operation and 6 months after surgery. Pain
      was assessed by means of a visual analogue scale 2 days and 6 months after
      surgery. The primary outcome measure was the feeling of a foreign body in the
      groin at 6 months. RESULTS: Some 122 hernias were randomized; 117 were included
      in the analysis of perioperative data, and 106 were re-examined after 6 months.
      There were no differences between the treatment groups with respect to early and
      late surgical complications. Use of lightweight mesh was associated with
      significantly less pain on exercise after 6 months (P = 0.042). In addition,
      fewer patients reported the feeling of a foreign body after repair with
      lightweight mesh (17.2 versus 43.8 per cent with conventional mesh; P = 0.003).
      Quality of life was improved significantly at 6 months compared with the
      preoperative assessment, and there were no differences between the treatment
      groups. CONCLUSION: Lightweight polypropylene mesh may be preferable for
      Lichtenstein repair of inguinal hernia. Larger cohorts with longer follow-up are
      needed before it can be recommended for routine use.

PMID- 14716793
TI  - Diagnostic delay in breast cancer.
AB  - BACKGROUND: Delay in the diagnosis of breast cancer has important clinical and
      medicolegal implications. This study assessed the frequency, causes and effects
      of delay in the diagnosis of breast cancer in a specialist breast unit. METHODS:
      Details of women who attended the breast clinic between 1988 and 1999 inclusive,
      and for whom the interval between first attendance and diagnosis of invasive
      breast cancer was greater than 2 months, were reviewed. Potential causes of delay
      were identified and the consequence of the delay assessed. The clinical features
      were compared with those of patients diagnosed with breast cancer during a 2-year
      period from 1999 and 2001. RESULTS: Breast cancer was diagnosed in 5283 women
      during the interval reviewed; delay in diagnosis was suggested in 72 women (1.4
      per cent). Women with a delayed diagnosis were younger (P < 0.001) and had a
      smaller tumour at diagnosis (P = 0.011) compared with all women diagnosed with
      breast cancer between 1999 and 2001. There were no differences in the rate of
      axillary node positivity or the need for mastectomy. Women unsuitable for
      conservation therapy in the delayed group had a significantly longer interval to
      diagnosis (P = 0.006). CONCLUSION: The likelihood that conservation therapy will
      be appropriate is reduced when the hospital delay in the diagnosis of breast
      cancer is more than 240 days. All patients with a palpable mass require triple
      assessment to minimize delay in diagnosis of breast cancer.

PMID- 14716794
TI  - Randomized clinical trial investigating the use of drains and fibrin sealant
      following surgery for breast cancer.
AB  - BACKGROUND: Despite limited evidence, closed suction drainage is often used to
      reduce the risk of seroma formation after breast cancer surgery. The aim of this
      study was to evaluate the effect of drains and fibrin sealant on the incidence of
      seroma formation. METHODS: A total of 116 patients undergoing surgery for breast
      cancer were randomized to receive suction drainage (group 1; n = 58), or to
      receive no drain (n = 58). Patients allocated to receive no drain were further
      randomized to have fibrin sealant applied to the dissected area (group 2; n =
      29), or to no intervention (group 3; n = 29). Outcome measures were incidence and
      volume of postoperative seroma, length of hospital stay and postoperative pain
      scores. RESULTS: There was no significant difference in the incidence of seroma
      between group 1 (15 of 58) and either group with no drains (ten of 29 in group 2;
      12 of 29 in group 3). There was a significant reduction in hospital stay and
      postoperative pain scores in patients who did not have a drain. Following
      mastectomy without a drain, the use of fibrin sealant was associated with a
      significant reduction in the incidence and total volume of seroma (190 versus 395
      ml; P = 0.012). CONCLUSION: Drains did not prevent seroma formation, and were
      associated with a longer postoperative stay and higher pain scores after surgery
      for breast cancer. In patients who had mastectomy the use of fibrin sealant
      reduced the rate of seroma formation.

PMID- 14716795
TI  - Interleukin 7 induces the growth of breast cancer cells through a wortmannin
      sensitive pathway.
AB  - BACKGROUND: Interleukin (IL) 7 is a growth factor able to induce the growth and
      development of certain haematopoietic malignancies including lymphoma and
      leukaemia. Its effects on solid tumours, including breast cancer, are unknown.
      This report concerns the effect of IL-7 on the growth of breast cancer cells.
      METHODS: Reverse transcription-polymerase chain reaction, western blotting and
      immunoprecipitation were used to detect to detect IL-7 and its receptor (IL-7R)
      in breast cancer cell lines MDA MB-231 and MCF-7. These cells were treated with
      various concentrations of human recombinant IL-7 over specified intervals.
      Changes in growth were assessed using colorimetric and fluorescence-based
      technologies. Selective IL-7 downstream signalling inhibitors (wortmannin, JAK-3
      inhibitor 1, piceatanol and AG 490) were use to clarify the pathways through
      which IL-7 may affect breast cancer growth. RESULTS: IL-7 significantly
      accelerated the growth of MDA MB-231 cells and MCF-7 cells (P = 0.004 and P =
      0.012, respectively, in PicoGreenassay). The maximum effects were observed after
      incubation for 72 h. The stimulatory effect of IL-7 on cell growth was completely
      eliminated in the presence of wortmannin (P = 0.001 and P = 0.003 versus no
      inhibitor in MDA MB-231 and MCF-7 cells, respectively) and JAK-3 inhibitor 1 (P <
      0.001 versus no inhibitor in both cell lines), but not in the presence of
      piceatanol and AG 490. CONCLUSION: IL-7 induced the growth of breast cancer cells
      in vitro through a wortmannin-sensitive pathway. This may have an important
      impact on research into breast cancer development and progression.

PMID- 14716796
TI  - Subaxillary dermocutaneous fat flap for reconstruction of the upper outer
      quadrant of the breast following conservation surgery.

PMID- 14716797
TI  - Increased vascular endothelial growth factor production in fibroblasts isolated
      from strictures in patients with Crohn's disease.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      factor that is implicated in early wound healing and fibrosis. Fibroblasts may
      initiate stricture formation in Crohn's disease through overexpression of VEGF.
      The aim of this study was to examine VEGF expression and regulation in
      fibroblasts isolated from patients with Crohn's disease. METHODS: Fibroblasts
      were isolated by a primary explant technique from serosal biopsies of non
      strictured and strictured segments of bowel from eight patients undergoing
      resection for Crohn's disease, and normal colon from six patients undergoing
      resection for benign and malignant colorectal disease. Fibroblasts were cultured
      with transforming growth factor (TGF) beta and corticosteroids. After 24 h the
      culture supernatant was collected for VEGF assay by enzyme-linked immunosorbent
      assay. RESULTS: VEGF production was significantly higher in fibroblasts isolated
      from strictures (mean(s.e.m.) 1980(260) pg/ml) than from non-strictured segments
      (1116(165) pg/ml) in patients with Crohn's disease or control fibroblasts
      (898(93) pg/ml). TGF-beta increased VEGF production in normal and non-strictured
      Crohn's fibroblasts. Corticosteroids suppressed unstimulated VEGF production in
      all groups. CONCLUSION: Enhanced serosal fibroblast VEGF production might play a
      role in initiating stricture formation in Crohn's disease. VEGF production in
      serosal fibroblasts is sensitive to stimulation with TGF-beta. Corticosteroids
      may reduce stricturing through suppression of VEGF.

PMID- 14716798
TI  - Focused parathyroid surgery with intraoperative parathyroid hormone measurement
      as a day-case procedure.
AB  - BACKGROUND: This study assessed the feasibility, efficacy and safety of focused
      parathyroidectomy combined with intraoperative parathyroid hormone (IOPTH)
      measurement in a day-case setting. METHODS: Over 28 months 50 consecutive
      patients (mean age 63 (range 33-92) years) with clear evidence of unifocal
      disease on sestamibi scanning or ultrasonography underwent unilateral neck
      exploration via a small lateral incision. Blood samples for measurement of IOPTH
      were taken at induction of anaesthesia, before adenoma excision and after adenoma
      excision (at 5, 10 and 20 min). Ten patients were discharged within 23 h and 40
      patients on the day of surgery. RESULTS: A solitary adenoma was identified in all
      but one patient, with a mean operating time of 30 (range 16-57) min. After
      parathyroidectomy, IOPTH levels fell appropriately except in one patient with
      multiglandular hyperplasia. No patient developed symptomatic hypocalcaemia during
      the 2 weeks after operation, enabling cessation of oral supplements. All patients
      remained normocalcaemic on follow-up (mean 26 (range 8-84) weeks) and
      histological examination confirmed parathyroid adenoma (48 patients), hyperplasia
      (one) or carcinoma (one). CONCLUSION: After accurate preoperative localization of
      uniglandular disease, patients with primary hyperparathyroidism may be managed
      successfully and safely by focused parathyroidectomy with IOPTH measurement as a
      day-case procedure.

PMID- 14716799
TI  - Damage control laparotomy.
AB  - BACKGROUND: Damage Control Surgery (DCS) is well established in the management of
      trauma. This study assessed the results of DCS in the management of critically
      ill patients who had not had trauma. METHODS: This was a prospective series of
      patients treated by DCS. The Physiological and Operative Severity Score for the
      enUmeration of Mortality and morbidity (POSSUM) and Portsmouth predictor equation
      (P-POSSUM) were used to predict the risk of death, which was compared with the
      observed mortality rate. RESULTS: Fourteen patients were studied. Nine had sepsis
      from gastrointestinal perforation. Eight of these underwent bowel resection
      without anastomosis or stoma formation at the initial laparotomy. Six patients
      later underwent bowel anastomosis and two had an end stoma formed at second
      laparotomy. A further three patients had a ruptured aortic aneurysm, one had a
      reactionary haemorrhage after elective aortic surgery, and one had a
      retroperitoneal bleed; all required haemostatic packing that was removed at
      second laparotomy. Mortality rates predicted by POSSUM and P-POSSUM scoring were
      64.5 and 49.6 per cent respectively. One patient (7.1 per cent) died after
      operation, giving an observed mortality rate significantly lower than predicted
      (P = 0.002 and P = 0.038 versus values predicted by POSSUM and P-POSSUM,
      respectively). CONCLUSION: The use of DCS in the treatment of critically ill
      patients resulted in a lower mortality rate than that predicted by POSSUM or P
      POSSUM. DCS should not be restricted to trauma.

PMID- 14716800
TI  - Genetic approach to the role of cysteine proteases in the expansion of abdominal
      aortic aneurysms.
AB  - BACKGROUND: The elastinolytic cysteine proteases, including cathepsins S and K,
      are overexpressed at sites of arterial elastin damage. Cystatin C, an inhibitor
      of these enzymes, is expressed in arterial smooth muscle cells; an imbalance in
      cystatin C has been implicated in the aortic wall degeneration observed in
      abdominal aortic aneurysms (AAAs). The aim of the study was to investigate the
      impact of a polymorphism in the signal peptide of the cystatin C gene on the
      growth of small AAAs. METHODS: Some 424 patients with a small AAA (4.0-5.5 cm)
      were monitored for AAA growth by ultrasonography and provided a DNA sample for
      analysis of the + 148 G > A polymorphism in the cystatin C signal peptide and the
      82 G > C polymorphism in the gene promoter. The median length of follow-up was
      2.8 years and AAA growth rates were calculated by linear regression analysis.
      RESULTS: For patients of + 148 GG (n = 263), GA (n = 147) and AA (n = 20)
      genotypes, the mean(s.d.) AAA growth rates were 0.37(0.29), 0.37(0.23) and
      0.30(0.26) cm, and initial diameters were 4.58(0.35), 4.58(0.35) and 4.62(0.36)
      cm, respectively. Patients of + 148 AA genotype had a slower aneurysm growth rate
      (unadjusted P = 0.058; after adjustment for age, sex, initial AAA diameter and
      smoking, P = 0.027). There also was a trend for the rare homozygotes of the-82 C
      allele to have slower AAA growth (adjusted P = 0.055). Smoking history had a
      stronger association with aneurysm growth (P = 0.003). CONCLUSION: There was a
      weak association between variation in the cystatin C gene and AAA growth. Medical
      strategies to limit AAA growth might include the inhibition of cysteine
      proteases.

PMID- 14716801
TI  - Surgical treatment for cancer of the oesophagus and gastric cardia in Hebei,
      China.
AB  - BACKGROUND: Southern Hebei Province has one of the highest incidences of
      oesophageal cancer in the world. This study describes a single-centre experience
      with oesophagectomy for this condition. METHODS: The reported articles on
      surgical treatment for cancer of the oesophagus and gastric cardia from a single
      department between September 1952 and December 2000 were summarized and the
      results compared. RESULTS: Between September 1952 and December 2000, the
      resectability rate increased from 78.8 to 96.0 per cent for oesophageal cancer
      and from 69.6 to 94.8 per cent for cancer of the cardia. The surgical mortality
      rate decreased from 4.6 to 1.1 per cent. There was little change in the overall 5
      year survival rate; it increased from 21.2 to 23.9 per cent for patients with
      oesophageal cancer and from 15.2 to 17.6 per cent for those with cancer of the
      cardia. CONCLUSION: The rate of postoperative complications and deaths following
      oesophagectomy for cancer has fallen steadily over the past five decades but long
      term survival remains disappointing. Improved survival is likely to be dependent
      on earlier diagnosis and adjunctive therapies.

PMID- 14716802
TI  - An intraductal papillary component is associated with prolonged survival after
      hepatic resection for intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The outcome after surgery for intrahepatic cholangiocarcinoma (ICC)
      is dismal and data on long-term survival are not available. This study evaluated
      prognostic indicators and characteristic features of long-term survivors after
      hepatic resection for ICC. METHODS: Thirty-one patients who had undergone hepatic
      resection for ICC were studied. Univariate and multivariate survival analyses of
      clinicopathological data included an intraductal papillary carcinoma component
      (IDPCC) in the tumour, which was defined as the histological demonstration of
      cancer cells growing in a papillary fashion into the lumen of the large bile
      duct. RESULTS: The overall cumulative survival rate after hepatic resection for
      ICC was 51.2 per cent at 1 year and 24.5 per cent at 5 years, with a mean(s.d.)
      survival time of 11(4) months. The presence of IDPCC (P = 0.003), curative
      resection (P = 0.009) and the absence of perineural invasion (P = 0.040) were
      identified as favourable independent prognostic factors in multivariate analysis.
      Eight patients with IDPCC had a 5-year survival rate of 87.5 per cent and a
      mean(s.d.) survival time of 69(13) months. All seven patients who survived for
      more than 5 years after surgery had IDPCC, regardless of the gross appearance of
      the tumour. CONCLUSION: An IDPCC in the tumour resulted in long-term survival
      after hepatic resection for ICC.

PMID- 14716803
TI  - Surgical site infection after groin hernia repair.
AB  - BACKGROUND: Post-discharge surveillance for 30 days is needed to determine the
      true incidence of surgical site infection (SSI). This study was undertaken to
      determine the incidence of, and risk factors for, SSI after hernia repair.
      METHODS: A total of 3150 patients who had undergone groin hernia repair in 32
      Scottish hospitals were telephoned 10, 20 and 30 days after operation to screen
      for SSI. Patients who believed the wound to be infected were seen by a healthcare
      worker to confirm the diagnosis. Details of operations and risk factors were
      obtained by case-note review. RESULTS: One hundred and four patients (3.3 per
      cent) declined to give a contact telephone number, leaving 3046 patients who
      agreed to take part in the study. Some 108 patients (3.4 per cent) could not be
      contacted at any point, giving a response rate of 93.3 per cent. Complete data
      were available for 2665 patients (87.5 per cent); 140 (5.3 per cent) developed
      SSI and 57 (2.1 per cent) thought the wound infected but this was not confirmed
      by the healthcare worker. Patients given a prophylactic antibiotic had a lower
      incidence of SSI (P = 0.002), but neither increase in the American Society of
      Anesthesiologists grade of fitness for operation nor prolonged duration of
      operation was a significant risk factor for infection. CONCLUSION: SSI after
      hernia repair is common and large clinical trials are required to determine
      whether the use of prophylactic antibiotics reduces the incidence of infection.

PMID- 14716804
TI  - Preoperative probability model for predicting overall survival after resection of
      pulmonary metastases from colorectal cancer.
AB  - BACKGROUND: The aim of this study was identify readily available factors most
      helpful in predicting survival and to develop a prognostic nomogram for patients
      with pulmonary metastases from colorectal cancer who are candidates for
      thoracotomy. METHODS: Pretreatment data on 313 patients with metastases who
      underwent thoracotomy were analysed. Fourteen preoperative clinical and
      pathological variables were used to develop a probability model, in which their
      association with 3-year survival was tested. A nomogram to predict median, 1- and
      3-year survival was constructed and validated internally using the concordance
      index (c-index). The nomogram was then validated with an external data set.
      RESULTS: Five variables were identified as independent predictors of 3-year
      survival: prethoracotomy carcinoembryonic antigen level, number of pulmonary
      tumours, presence of hilar or mediastinal tumour-infiltrated lymph nodes,
      histology of the primary tumour and presence of extrathoracic disease. The
      nomogram was well calibrated for predicting 3-year overall survival. The internal
      validated c-index of the nomogram was 0.72. Applied to another data set, the
      external validated c-index was 0.66. CONCLUSION: This model has moderate
      predictive ability to discriminate between patients who are likely to survive
      after thoracotomy for pulmonary metastases from colorectal cancer.

PMID- 14716805
TI  - Optimal total mesorectal excision for rectal cancer is by dissection in front of
      Denonvilliers' fascia.

PMID- 14716806
TI  - Letter 3 (for Letters 1 and 2 see Br J Surg 2003; 90: 1451 - 1452): cold
      provocation testing and hand-arm vibration syndrome - an audit of the results of
      the Department of Trade and Industry scheme for the evaluation of miners (Br J
      Surg 2003; 90: 1076-1079).

PMID- 14716808
TI  - Randomized clinical trial comparing epidural anaesthesia and patient-controlled
      analgesia after laparoscopic segmental colectomy (Br J Surg 2003; 90: 1195-1199).

PMID- 14716810
TI  - Anastomotic leakage after curative anterior resection results in a higher
      prevalence of local recurrence colectomy (Br J Surg 2003; 90: 1261-1266).

PMID- 14716811
TI  - Gastrointestinal stromal tumours (Br J Surg 2003; 90: 1178- 1186).

PMID- 14716814
TI  - Effect of staurosporine on cycle of human gastric cancer cells.
AB  - AIM: To study the effect of staurosporine (ST) on the cell cycle of human gastric
      cancer cell lines MGC803 and SGC7901. METHODS: Cell proliferation was evaluated
      by trypan blue dye exclusion method. Apoptotic morphology was observed under a
      transmission electron microscope. Changes of cell cycle and apoptotic peaks of
      cells were determined by flow cytometry. Expression of p21WAF1 gene was examined
      using immunohistochemistry and RT-PCR. RESULTS: The growth of MGC803 and SGC7901
      cells was inhibited by ST. The inhibitory concentrations against 50% cells (IC50)
      at 24 h and 48 h were 54 ng/ml and 23 ng/ml for MGC803, and 61 ng/ml and 37 ng/ml
      for SGC7901. Typical apoptotic bodies and apoptotic peaks were observed 24 h
      after cells were treated with ST at a concentration of 200 ng/ml. The percentage
      of cells at G0/G1 phase was decreased and that of cells at G2/M was increased
      significantly in the group treated with ST at the concentrations of 40 ng/ml, 60
      ng/ml, 100 ng/ml for 24 h, compared with the control group (P<0.01). The
      expression levels of p21WAF1 gene in both MGC803 and SGC7901 cells were markedly
      up-regulated after treatment with ST. CONCLUSION: ST can cause arrest of gastric
      cancer cells at G2/M phase, which may be one of the mechanisms that inhibit cell
      proliferation and cause apoptosis in these cells. Effect of ST on cells at G2/M
      phase may be attributed to the up-regulation of p21WAF1 gene.

PMID- 14716813
TI  - ATM and ATR: sensing DNA damage.
AB  - Cellular response to genotoxic stress is a very complex process, and it usually
      starts with the "sensing" or "detection" of the DNA damage, followed by a series
      of events that include signal transduction and activation of transcription
      factors. The activated transcription factors induce expressions of many genes
      which are involved in cellular functions such as DNA repair, cell cycle arrest,
      and cell death. There have been extensive studies from multiple disciplines
      exploring the mechanisms of cellular genotoxic responses, which have resulted in
      the identification of many cellular components involved in this process,
      including the mitogen-activated protein kinases (MAPKs) cascade. Although the
      initial activation of protein kinase cascade is not fully understood, human
      protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3
      related) are emerging as potential sensors of DNA damage. Current progresses in
      ATM/ATR research and related signaling pathways are discussed in this review, in
      an effort to facilitate a better understanding of genotoxic stress response.

PMID- 14716815
TI  - Inhibition of beta-ionone on SGC-7901 cell proliferation and upregulation of
      metalloproteinases-1 and -2 expression.
AB  - AIM: To observe the effect of beta-ionone on the proliferation of human gastric
      adenocarcinoma cell line SGC-7901 and the inhibition of metalloproteinase.
      METHODS: Using growth inhibition, Zymograms assays and reverse transcription
      polymerase-chain reaction (RT-PCR), we examined cell growth rates, activities of
      matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9), and expression of
      metalloproteinases-1 (TIMP-1) and -2 (TIMP-2) in SGC-7901 cells after the
      treatment with beta-ionone for 24 h and 48 h, respectively. RESULTS: beta-ionone
      had an inhibitory effect on the growth of SGC-7901 cells. Eight days after the
      treatment with beta-ionone at concentrations of 25, 50, 100 and 200 micromol/L,
      the inhibition rates were 25.9%, 28.2%, 74.4% and 90.1%, respectively. The IC50
      value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The
      effects of beta-ionone on MMP-2 and MMP-9 activities in SGC-7901 cells were not
      observed. However, the levels of TIMP-1 and TIMP-2 transcripts were elevated in
      cells treated with beta-ionone in a dose-dependent manner. CONCLUSION: beta
      ionone can inhibit the proliferation of SGC-7901 cells, upregulate the expression
      of TIMP-1 and TIMP-2 expression, and may influence metastasis of cancer.

PMID- 14716816
TI  - Correlation of thymidylate synthase, thymidine phosphorylase and
      dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells
      to 5-fluorouracil and 5-fluoro-2'-deoxyuridine.
AB  - AIM: To determine the expression levels of three metabolic enzymes of
      fluoropyrimidines: thymidylate synthase (TS), thymidine phosphorylase (TP) and
      dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell
      lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5
      FU) and 5-fluoro-2'-deoxyuridine (FdUrd). METHODS: TS, TP and DPD mRNA levels
      were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were
      measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50),
      representing the sensitivity to drugs, were determined by MTT assay. RESULTS:
      IC50 values ranged from 1.28 to 12.26 microM for 5-FU, and from 5.02 to 24.21
      microM for FdUrd, respectively. Cell lines with lower DPD mRNA and protein levels
      tended to be more sensitive to 5-FU (P<0.05), but neither TS nor TP correlated
      with 5-FU IC50 (P>0.05). Only TS mRNA level was sharply related with FdUrd
      sensitivity (P<0.05), but TP and DPD were not (P>0.05). A correlation was found
      between mRNA and protein levels of DPD (P<0.05), but not TP (P<0.05). CONCLUSION:
      DPD and TS enzyme levels may be useful indicators in predicting the antitumor
      activity of 5-FU or FdUrd, respectively.

PMID- 14716817
TI  - Expression of NF-kappaB and human telomerase reverse transcriptase in gastric
      cancer and precancerous lesions.
AB  - AIM: To investigate the expression of NF-kappaBp65 protein and human telomerase
      reverse transcriptase (hTERT) and their correlation in gastric cancer and
      precancerous lesions. METHODS: Forty-one patients with primary gastric cancer, 15
      with dysplasia, 23 intestinal metaplasia and 10 with normal gastric mucosa were
      included in this study. Expression of NF-kappaBp65 protein, hTERT mRNA and
      protein were determined by immunohistochemistry and in situ hybridization.
      RESULTS: The rate of p65 expression in normal gastric mucosa, intestinal
      metaplasia, dysplasia and carcinoma was 0%, 34.78%, 53.33% and 60.98%,
      respectively, while the rate of hTERT mRNA expression was 10.00%, 39.13%, 66.67%
      and 85.37% and the rate of hTERT protein expression was 0%, 30.43%, 60.00% and
      78.05%, respectively. All the three parameters were significantly increased in
      dysplasia and carcinoma compared to normal mucosa, while the expression levels
      were also significantly higher in carcinoma than in intestinal metaplasia
      (P<0.05). In gastric cancer tissues, nuclear staining rates of p65 and hTERT
      protein were both significantly associated with the degree of differentiation,
      lymph node metastasis, clinical stage and invasion depth (P<0.05). However, hTERT
      mRNA expression was only significantly associated with clinical stage. There was
      a positive correlation between p65 and hTERT mRNA (rs=0.661-0.752, P<0.01), and
      between hTERT protein and hTERT mRNA (rs=0.609-0.750, P<0.01). CONCLUSION: NF
      kappaBp65 and hTERT expressions are upregulated at the early stage of gastric
      carcinogenesis. NF-kappaB activation may contribute to hTERT expression and
      thereby enhance telomerase activity, which represents an important step in
      carcinogenesis progress.

PMID- 14716818
TI  - Correlation of tumor-positive ratio and number of perigastric lymph nodes with
      prognosis of patients with surgically-removed gastric carcinoma.
AB  - AIM: To evaluate the tumor-positive ratio and number of perigastric lymph nodes
      as prognostic factors of gastric carcinoma in surgically-treated patients.
      METHODS: The postoperative survival of 169 patients with gastric cancer who were
      performed D2 curative gastrectomy was analyzed with regard to its lymph node
      metastasis ratio and number. Meanwhile correlation of tumor-positive ratio and
      number of perigastric lymph nodes with pathological parameters of these patients
      was studied. RESULTS: The overall 5-year survival rate of all the patients
      studied was 29.6%. The 5-year cumulative survival rate in patients with 1%-20%
      and more than 20% of tumor-positive lymph nodes was 70.6% and 12.0% respectively,
      and 46.6% and 17.4% in those with 1-5 and more than 5 of tumor-positive lymph
      nodes respectively, which were significantly decreased with the increment of
      involved lymph nodes assessed by either numbers or ratio (P<0.05). Multiple
      stepwise regression analysis showed that both the positive ratio and number of
      tumor-involved lymph nodes were sensitive prognostic factors in these surgically
      treated patients, which were also significantly correlated with tumor size and
      depth of submucosal invasion (P<0.05). CONCLUSION: Tumor-positive ratio and
      number of perigastric lymph nodes are associated with cancer progression and five
      year survival rate, and may serve as valuable prognostic factors of gastric
      cancer in surgically-treated patients.

PMID- 14716819
TI  - Construction of a targeting adenoviral vector carrying AFP promoter for
      expressing EGFP gene in AFP-producing hepatocarcinoma cell.
AB  - AIM: To construct a recombinant adenoviral vector carrying AFP promoter and EGFP
      gene for specific expression of EGFP gene in AFP producing hepatocellular
      carcinoma (HCC) HepG2 cells. METHODS: Based on the Adeno-X expression system, the
      human immediate early cytomegalovirus promoter (PCMV IE) was removed from the
      plasmid, pshuttle, and replaced by a 0.3 kb alpha-fetoprotein (AFP) promoter that
      was synthesized by polymerase chain reaction (PCR). The enhanced green
      fluorescent protein (EGFP) gene was inserted into the multi-clone site (MCS), and
      then the recombinant adenovirus vector carrying the 0.3 kb AFP promoter and EGFP
      gene was constructed. Cells of a normal liver cell line (LO2), a hepatocarcinoma
      cell line (HepG2) and a cervical cancer cell line (HeLa) were transfected with
      the adenovirus. Northern blot and fluorescence microscopy were used to detect the
      expression of the EGFP gene at mRNA or protein level in three different cell
      lines. RESULTS: The 0.3 kb AFP promoter was synthesized through PCR from the
      human genome. The AFP promoter and EGFP gene were directly inserted into the
      plasmid pshuttle as confirmed by restriction digestion and DNA sequencing.
      Northern blot showed that EGFP gene was markedly transcribed in HepG2 cells, but
      only slightly in LO2 and HeLa cells. In addition, strong green fluorescence was
      observed in HepG2 cells under a fluorescence microscopy, but fluorescence was
      very weak in LO2 and HeLa cells. CONCLUSION: Under control of the 0.3 kb human
      AFP promoter, the recombinant adenovirus vector carrying EGFP gene can be
      specially expressed in AFP-producing HepG2 cells. Therefore, this adenovirus
      system can be used as a novel, potent and specific tool for gene-targeting
      therapy for the AFP positive primary hepatocellular carcinoma.

PMID- 14716820
TI  - Effects of p53 on apoptosis and proliferation of hepatocellular carcinoma cells
      treated with transcatheter arterial chemoembolization.
AB  - AIM: To evaluate the effects of p53 on apoptosis and proliferation of
      hepatocellular carcinoma (HCC) cells treated with transcatheter arterial
      chemoembolization (TACE). METHODS: A total of 136 patients with HCC received TACE
      and other management before surgery were divided into TACE group and non-TACE
      group. TACE group included 79 patients who had 1-5 courses of TACE before
      surgery, of them, 11 patients had 1-4 courses of chemotherapy (group A), 33
      patients had 1-5 courses of chemotherapy combined with iodized oil (group B), 23
      patients had 1-3 courses of chemotherapy, iodized oil and gelatin sponge (group
      C), 12 patients had 1-3 courses of chemotherapy combined with iodized oil,
      ethanol and gelatin sponge (group D). Non-TACE group included the remaining 57
      patients who had surgery only. The extent of apoptosis was analyzed by
      transferase mediated dUTP nick end labeling (TUNEL) staining. The expressions of
      p53, Bcl-2, Bax, Ki-67 and PCNA protein were detected by immunohistochemical
      method. RESULTS: P53 protein expressions in trabecular and clear cells in HCC
      specimens were significantly lower than that in pseudoglandular, solid, poorly
      differentiated or undifferentiated and sclerosis HCC (P<0.05). Expression of p53
      protein in HCC cells increased with the increase of pathological grades (P<0.05),
      and correlated positively with expressions of Ki-67 and PCNA protein, and
      negatively with Bcl-2 to Bax protein expression rate and AI (P<0.05). Expression
      of p53 protein was significantly higher in group A than in groups B, C, D and the
      non-TACE group, and was higher in group B than in groups C and D, and lower in
      group D than in the non-TACE group (P<0.05). CONCLUSION: Expression of p53
      protein can enhance proliferation of HCC cells and suppress apoptosis of HCC
      cells after TACE.

PMID- 14716821
TI  - Expression of co-stimulator 4-1BB molecule in hepatocellular carcinoma and
      adjacent non-tumor liver tissue, and its possible role in tumor immunity.
AB  - AIM: To investigate the expression of 4-1BB molecule in hepatocellular carcinoma
      (HCC) and its adjacent tissues. METHODS: Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to determine the gene expression of 4-1BB in
      hepatocarcinoma and its adjacent tissues, and peripheral blood mononuclear cells
      (PBMCs) from both HCC and health control groups. Flow cytometry was used to
      analyse the phenotypes of T cell subsets from the blood of HCC patients and
      healthy volunteers, and further to determine whether 4-1BB molecules were also
      expressed on the surface of CD4+ and CD8+ T cells. The localization of 4-1BB
      proteins on tumor infiltrating T cells was determined by direct
      immunofluorescence cytochemical staining and detected by confocal microscopy.
      RESULTS: 4-1BB mRNA, which was not detectable in normal liver, was found in 19
      liver tissues adjacent to tumor edge (<1.0 cm). Low expression of 4-1BB mRNA was
      shown in 8 tumor tissues and 6 liver tissues located within 1 to 5 cm away from
      tumor edge. In PBMCs, 4-1BB mRNA was almost not detected. Percentage of CD4+,
      CD8+ and CD3+/CD25+ T cells, as well as ratio of CD4 to CD8 revealed no
      difference between groups (P>0.05, respectively), while a significant lower
      percentage of CD3+ T cell was found in HCC group as compared to healthy control
      group (P<0.05). However, 4-1BB molecules were almost not found on the surface of
      CD4+ and CD8+ T cells in HCC and healthy control group. Double-staining of 4
      1BB+/CD4+ and 4-1BB+/CD8+ immunofluorescence on tumor infiltrating T cells was
      detected in 13 liver tissues adjacent to tumor edge (<1.0 cm) by confocal
      microscopy. CONCLUSION: Although HCC may escape from immune attack by weak
      immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell
      surface, tumor infiltrating T cells can be activated via other costimulatory
      signal pathways to exert a limited antitumor effect on local microenvironment.
      The present study also implicates that modulating 4-1BB/4-1BBL costimulatory
      pathway may be an effective immunotherapy strategy to augment the host response.

PMID- 14716822
TI  - Antitumor immunopreventive effect in mice induced by DNA vaccine encoding a
      fusion protein of alpha-fetoprotein and CTLA4.
AB  - AIM: To develop a tumor DNA vaccine encoding a fusion protein of murine AFP and
      CTLA4, and to study its ability to induce specific CTL response and its
      protective effect against AFP-producing tumor. METHODS: Murine alpha-fetoprotein
      (mAFP) gene was cloned from total RNA of Hepa1-6 cells by RT-PCR. A DNA vaccine
      was constructed by fusion murine alpha-fetoprotein gene and extramembrane domain
      of murine CTLA4 gene. The DNA vaccine was identified by restriction enzyme
      analysis, sequencing and expression. EL-4 (mAFP) was developed by stable
      transfection of EL-4 cells with pmAFP. The frequency of cells producing IFN-gamma
      in splenocytes harvested from the immunized mice was measured by ELISPOT. Mice
      immunized with DNA vaccine were inoculated with EL-4 (mAFP) cells in back to
      observe the protective effect of immunization on tumor. On the other hand, blood
      samples were collected from the immunized mice to check the functions of liver
      and kidney. RESULTS: 1.8 kb mAFP cDNA was cloned from total RNA of Hepa1-6 cells
      by RT-PCR. The DNA vaccine encoding a fusion protein of mAFP-CTLA4 was
      constructed and confirmed by restriction enzyme analysis, sequencing and
      expression. The expression of mAFP mRNA in EL-4 (mAFP) was confirmed by RT-PCR.
      The ELISPOT results showed that the number of IFN-gamma-producing cells in pmAFP
      CTLA4 group was significantly higher than that in pmAFP, pcDNA3.1 and PBS group.
      The tumor volume in pmAFP-CTLA4 group was significantly smaller than that in
      pmAFP, pcDNA3.1 and PBS group, respectively. The hepatic and kidney functions in
      each group were not altered. CONCLUSION: AFP-CTLA4 DNA vaccine can stimulate
      potent specific CTL responses and has distinctive antitumor effect on AFP
      producing tumor. The vaccine has no impact on the function of mouse liver and
      kidney.

PMID- 14716823
TI  - Enhancement of osteopontin expression in HepG2 cells by epidermal growth factor
      via phosphatidylinositol 3-kinase signaling pathway.
AB  - AIM: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions
      including cancer development, progression and metastasis. It is unclear how
      osteopontin is regulated in HepG2 cells. The aim of this study was to investigate
      the effect of epidermal growth factor on the expression of osteopontin in HepG2
      cells, and to explore the signal transduction pathway mediated this expression.
      METHODS: Osteopontin expression was detected by RNAase protection assay and
      Western blot. Wortmannin, a specific inhibitor of PI3K, was used to see if PI3K
      signal transduction was involved in the induction of osteopontin gene expression.
      RESULTS: HepG2 cells constitutively expressed low levels of osteopontin.
      Treatment with epidermal growth factor increased osteopontin mRNA and protein
      level in a dose- and time-dependent manner. Application of wortmannin caused a
      dramatic reduction of epidermal growth factor-induced osteopontin expression.
      CONCLUSION: Osteopontin gene expression can be induced by treatment of HepG2
      cells with epidermal growth factor. Epidermal growth factor may regulate
      osteopontin gene expression through PI3K signaling pathway. Several potential
      targets in the pathway can be manipulated to block the synthesis of osteopontin
      and inhibit liver cancer metastasis.

PMID- 14716824
TI  - Genetic detection of Chinese hereditary nonpolyposis colorectal cancer.
AB  - AIM: To explore the germline mutations of the two main DNA mismatch repair genes
      (hMSH2 and hMLH1) between patients with hereditary non-polyposis colorectal
      cancer (HNPCC) and suspected (atypical) HNPCC. METHODS: Genomic DNA was extracted
      from the peripheral blood of the index patient of each family, and germline
      mutations of hMSH2 and hMLH1 genes were detected by PCR-single strand
      conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. RESULTS: For
      PCR-SSCP analysis, 67% (4/6) abnormal exons mobility in typical group and 33%
      (2/6) abnormal exons mobility in atypical group were recognized. In direct DNA
      sequencing, 50% (3/6) mutation of MMR genes in typical group and 33% (2/6)
      mutation of MMR genes in atypical group were found, and 4/6 (66.67%) and 1/6
      (16.67%) mutations of hMSH2 and hMLH1 were identified in typical HNPCC and
      atypical HNPCC, respectively. CONCLUSION: Mutation detection of the patients is
      of benefit to the analysis of HNPCC and, PCR-SSCP is an effective strategy to
      detect the mutations of HNPCC equivalent to direct DNA sequence. It seems that
      there exist more complicated genetic alterations in Chinese HNPCC patients than
      in Western countries.

PMID- 14716825
TI  - Expression of estrogen receptor beta in human colorectal cancer.
AB  - AIM: To determine the expression of estrogen receptor (ER) beta in Chinese
      colorectal carcinoma (CRC) patients. METHODS: ERbeta expression in CRC was
      investigated by immunohistochemical staining of formalin-fixed, paraffin-embedded
      tissue sections from 40 CRCs, 10 colonic adenomas, and 10 normal colon mucosa
      biopsies. The percentage of positive cells was recorded, mRNA expression of
      ERalpha and ERbeta in 12 CRC tissues and paired normal colon tissues were
      detected by RT-PCR. RESULTS: Positive ER immunoreactivity was present in part of
      normal epithelium of biopsy (2/10), adenomas (3/10), and the sections of CRC
      tissue, most of them were nuclear positive. In CRCs, nuclear ERbeta
      immunoreactivity was detected in over 10% of the cancer cells in 57.5% of the
      cases and was always associated with cytoplasmic immunoreactivity. There was no
      statistical significance between ERbeta positive and negative groups in regard to
      depth of invasion and nodal metastases. Of the 12 CRC tissues and paired normal
      colon tissues, the expression rate of ERalpha mRNA in CRC tissue and
      corresponding normal colon tissue was 25% and 16.6%, respectively. ERbeta mRNA
      was expressed in 83.3% CRC tissue and 91.7% paired normal colon tissue,
      respectively. There was no significant difference in ERbeta mRNA level between
      CRC tissues and paired normal colon tissues. CONCLUSION: A large number of CRCs
      are positive for ERbeta, which can also be detected in normal colonic epithelia.
      There is a different localization of ERbeta immunoreactivity among normal colon
      mucosae, adenomas and CRCs. ERalpha and ERbeta mRNA can be detected both in CRC
      tissue and in corresponding normal colon tissue. A post-transcriptional mechanism
      may account for the decrease of ERbeta protein expression in CRC tissues.

PMID- 14716826
TI  - Ethylene diamine tetraacetic acid-induced colonic crypt cell proliferation in
      rats.
AB  - AIM: To investigate the effect of ethylene diamine tetraacetic acid (EDTA) on
      proliferation of rat colonic cells. METHODS: EDTA was administered into Wistar
      rats, carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats was studied
      with immunohistochemistry. RESULTS: Marked regional differences in cell
      proliferation were found in all groups. In EDTA-treated animals, total labelling
      indexes in both proximal (10.00 +/- 0.44 vs 7.20 +/- 0.45) and distal (11.05 +/-
      0.45 vs 8.65 +/- 0.34) colon and proliferative zone size (21.67 +/- 1.13 vs 16.75
      +/- 1.45, 27.73 +/- 1.46 vs 21.74 +/- 1.07) were significantly higher than that
      in normal controls (P<0.05) and lower than that in DMH group (10.00 +/- 0.44 vs
      11.54 +/- 0.45, 11.05 +/- 0.45 vs 13.13 +/- 0.46, 21.67 +/- 1.13 vs 35.52 +/-
      1.58, 27.73 +/- 1.46 vs 39.61 +/- 1.32, P<0.05). Cumulative frequency
      distributions showed a shift of the EDTA distal curve to the right (P<0.05) while
      the EDTA proximal curve did not change compared to normal controls. Despite the
      changes of proliferative parameters, tumours did not develop in EDTA treated
      animals. CONCLUSION: Hyperproliferation appears to be more easily induced by EDTA
      in distal colon than in proximal colon. Hyperproliferation may need to exceed a
      threshold to develop colonic tumours. EDTA may work as a co-factor in colonic
      tumorigenesis.

PMID- 14716827
TI  - Low grade gastric mucosa associated lymphoid tissue lymphoma: treatment
      strategies based on 10 year follow-up.
AB  - AIM: To deduce strategic guidelines of gastric mucosa associated lymphoid tissue
      lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to
      various treatment modalities. METHODS: A total of 55 patients with MALTOMA from
      May 1992 to August 2002 were retrospectively reviewed. RESULTS: Complete
      remission was obtained in 24 (82.8%) of 29 patients treated with anti
      Helicobacter pylori (H pylori) regimen only. The duration to reach complete
      remission was 12 months (85 percentile, 2-33 months). Five patients showed
      complete remission with radiation therapy (26-86 months). Two of them were H
      pylori treatment failure cases. CONCLUSION: H pylori eradication is an effective
      primary treatment option for low grade MALTOMA and radiation therapy could be
      considered in patients with no evidence of H pylori infection or who do not
      respond to H pylori eradication therapy 12 months after successful eradication.

PMID- 14716828
TI  - Effect of Helicobacter pylori infection on expression of Bcl-2 family members in
      gastric adenocarcinoma.
AB  - AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on the
      expressions of Bcl-2 family members in gastric adenocarcinoma. METHODS: Gastric
      adenocarcinoma and resection margin tissues of 95 patients were studied. Semi
      quantitative RT-PCR was used to measure Bid, Bax and Bcl-2 mRNA expressions.
      RESULTS: Expressions of Bid and Bax in gastric adenocarcinoma tissues without H
      pylori infection, with cagA- H pylori infection and cagA+ H pylori infection
      increased significantly in turn (Bid, 0.304, 0.422 and 0.855 respectively,
      P<0.05; Bax, 0.309, 0.650 and 0.979 respectively, P<0.05). Bcl-2 mRNA levels
      increased significantly in gastric adenocarcinoma tissues with cagA- H pylori
      infection and cagA+ H pylori infection, compared with those without H pylori
      infection (0.696 and 0.849 vs 0.411, P<0.05). Expressions of Bid, Bax and Bcl-2
      in resection margin tissues without H pylori infection, with cagA- H pylori
      infection and cagA+ H pylori infection increased significantly in turn (Bid,
      0.377, 0.686 and 0.939 respectively, P<0.05; Bax, 0.353, 0.645 and 1.001
      respectively, P<0.05; Bcl-2, 0.371, 0.487 and 0.619 respectively, P<0.05). In H
      pylori negative specimens, expressions of Bid and Bax correlated negatively with
      that of Bcl-2 respectively in adenocarcinoma tissues (Bid vs Bcl-2, r=-0.409,
      P<0.05; Bax vs Bcl-2, r=-0.451, P<0.05). In H pylori positive specimens,
      expressions of Bid and Bax did not correlate with that of Bcl-2 in adenocarcinoma
      tissues (Bid vs Bcl-2, r=0.187, P>0.05; Bax vs Bcl-2, r=0.201, P>0.05), but
      correlated positively with that of Bcl-2 respectively in resection margin tissues
      (Bid vs Bcl-2, r=0.331, P<0.05; Bax vs Bcl-2, r=0.295, P<0.05). CONCLUSION: H
      pylori may enhance Bid, Bax and Bcl-2 mRNA levels and cause deregulation of these
      apoptosis-associated genes expressions, which may play a role during development
      of gastric adenocarcinoma induced by H pylori.

PMID- 14716829
TI  - Chinese literature associated with diagnosis of Helicobacter pylori.
AB  - AIM: To synthetically analyze and probe into the diagnosis of H pylori infection,
      we followed the principles of evidence-based medicine. METHODS: A total of 22
      papers of prevalence survey and case-control studies were selected for studying
      about diadynamic methods. Using meta-analysis, we analyzed the different
      diadynamic methods of H pylori in China. RESULTS: Through meta-analysis, among
      the five diadynamic methods, the accuracy of polymerase chain reaction (PCR) was
      the highest (98.47%) and PCR was the most sensitive method (Sp: 99.03%).
      CONCLUSION: Among the five diadynamic methods, the accuracy of PCR is the highest
      and PCR is the most sensitive method to diagnose the infection of H pylori.

PMID- 14716830
TI  - Stable expression of human cytochrome P450 2D6*10 in HepG2 cells.
AB  - AIM: Over 90% of drugs are metabolized by the cytochrome P-450 (CYP) family of
      liver isoenzymes. The most important enzymes are CYP1A2, 3A4, 2C9/19, 2D6 and
      2E1. Although CYP2D6 accounts for <2% of the total CYP liver enzyme content, it
      mediates metabolism in almost 25% of drugs. In order to study its enzymatic
      activity for drug metabolism, its cDNA was cloned and a HepG2 cell line stably
      expressing CYP2D6 was established. METHODS: Human CYP2D6 cDNA was amplified with
      reverse transcription-polymerase chain reaction (RT-PCR) from total RNA extracted
      from human liver tissue and cloned into pGEM-T vector. cDNA segment was
      identified by DNA sequencing and subcloned into a mammalian expression vector
      pREP9. A cell line was established by transfecting the recombinant plasmid of
      pREP9-CYP2D6 to hepatoma HepG2 cells. Expression of mRNA was validated by RT-PCR.
      Enzyme activity of catalyzing dextromethorphan O-demethylation in
      postmitochondrial supernatant (S9) fraction of the cells was determined by high
      performance liquid chromatography (HPLC). RESULTS: The cloned cDNA had 4 base
      differences, e.g. 100 C-T, 336 T-C, 408 C-G and 1 457 G-C, which resulted in
      P34S, and S486T amino acid substitutions, and two samesense mutations were 112 F
      and 136 V compared with that reported by Kimura et al (GenBank accession number:
      M33388). P34S and S486T amino acid substitutions were the characteristics of
      CYP2D6*10 allele. The relative activity of S9 fraction of HepG2-CYP2D6*10
      metabolized detromethorphan O-demethylation was found to be 2.31 +/- 0.19
      nmol/min(-1)/mg(-1) S9 protein (n=3), but was undetectable in parental HepG2
      cells. CONCLUSION: cDNA of human CYP2D6*10 can be successfully cloned. A cell
      line, HepG2-CYP2D6*10, expressing CYP2D6*10 mRNA and having metabolic activity,
      has been established.

PMID- 14716831
TI  - Dynamic changes of capillarization and peri-sinusoid fibrosis in alcoholic liver
      diseases.
AB  - AIM: To investigate the dynamic changes of capillarization and peri-sinusoid
      fibrosis in an alcoholic liver disease model induced by a new method. METHODS:
      Male SD rats were randomly divided into 6 groups, namely normal, 4 d, 2 w, 4 w, 9
      w and 11 w groups. The animals were fed with a mixture of alcohol for designated
      days and then decollated, and their livers were harvested to examine the
      pathological changes of hepatocytes, hepatic stellate cells, sinusoidal
      endothelial cells, sinusoid, peri-sinusoid. The generation of three kinds of
      extra cellular matrix was also observed. RESULTS: The injury of hepatocytes
      became severer as modeling going on. Under electronic microscope, fatty vesicles
      and swollen mitochondria in hepatocytes, activated hepatic stellate cells with
      fibrils could been seen near or around it. Fenestrae of sinusoidal endothelial
      cells were decreased or disappeared, sinusoidal basement was formed. Under light
      microscopy typical peri-sinusoid fibrosis, gridding-like fibrosis, broaden portal
      areas, hepatocyte's fatty and balloon denaturation, iron sediment, dot necrosis,
      congregated lymphatic cells and leukocytes were observed. Type I collagen showed
      an increasing trend as modeling going on, slightly recovered when modeling
      stopped for 2 weeks. Meanwhile, type IV collagen decreased rapidly when modeling
      began and recovered after modeling stopped for 2 weeks. Laminin increased as soon
      as modeling began and did not recover when modeling stopped for 2 weeks.
      CONCLUSION: The pathological changes of the model were similar to that of human
      ALD, but mild in degree. It had typical peri-sinusoid fibrosis, however,
      capillarization seemed to be instable. It may be related with the reduction of
      type IV collagen in the basement of sinusoid during modeling.

PMID- 14716832
TI  - Preparation and property analysis of a hepatocyte targeting pH-sensitive
      liposome.
AB  - AIM: To develop a hepatocyte targeting pH-sensitive liposome for drug delivery
      based on active targeting technology mediated by asialoglycoprotein receptors.
      METHODS: Four types of targeting molecules with galactose residue were
      synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome
      with integrated property of hepatocyte specificity and pH sensitivity. Liposome
      18-gal was selected with the best transfection activity through cellular uptake
      experiment. Property analysis was made through experiments of competitive
      inhibition of receptors, red blood cell hemolysis, in vitro cytotoxicity test by
      MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN
      on gene expression, etc. RESULTS: Liposome 18-gal had the desired properties of
      hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection
      efficiency. CONCLUSION: Liposome 18-gal can be further developed as a potential
      hepatocyte- targeting delivery system.

PMID- 14716833
TI  - Effects of estradiol on liver estrogen receptor-alpha and its mRNA expression in
      hepatic fibrosis in rats.
AB  - AIM: Estradiol treatment regulates estrogen receptor (ER) level in normal rat
      liver. However, little information is available concerning the role of estrogen
      in regulating liver ER in hepatic fibrosis in rats. The present study was
      conducted to determine whether estradiol treatment in CCl4-induced liver fibrosis
      of female and ovariectomized rats altered liver ERalpha and its mRNA expression,
      and to investigate the possible mechanisms. METHODS: Seventy female rats were
      divided into seven groups with ten rats in each. The ovariectomy groups were
      initiated with ovariectomies and the sham operation groups were initiated with
      just sham operations. The CCl4 toxic fibrosis groups received 400 mL/L CCl4
      subcutaneously at a dose of 2 mL/kg twice weekly. Estrogen groups were treated
      subcutaneously with estradiol 1 mg/kg, the normal control group and an
      ovariectomy group received injection of peanut oil vehicle twice weekly. At the
      end of 8 weeks, all the rats were killed to detect their serum and hepatic
      indicators, their hepatic collagen content, and liver ER and ER mRNA expression.
      RESULTS: Estradiol treatment in both ovariectomy and sham ovariectomy groups
      reduced liver levels of ALT (from 658 +/- 220 nkat/L to 311 +/- 146 nkat/L and
      540 +/- 252 nkat/L to 314 +/- 163 nkat/L, P<0.05) and AST (from 697 +/- 240
      nkat/L to 321 +/- 121 nkat/L and 631 +/- 268 nkat/L to 302 +/- 153 nkat/L,
      P<0.05), increased serum nitric oxide (NO) level (from 53.7 +/- 17.1 micromol/L
      to 93.3 +/- 24.2 micromol/L and 55.3 +/- 23.1 micromol/L to 87.5 +/- 23.6
      micromol/L, P<0.05) and hepatic nitric oxide synthase (NOS) activity (from 1.73
      +/- 0.71 KU/g to 2.49 +/- 1.20 KU/g and 1.65 +/- 0.46 KU/g to 2.68 +/- 1.17 KU/g,
      P<0.05), diminished the accumulation of hepatic collagen, decreased centrolobular
      necrotic areas as well as the inflammatory reaction in rats subjected to CCl4.
      The positive signal of ER and ER mRNA distributed in parenchymal and non
      parenchymal hepatic cells, especially near the hepatic centrolobular and
      periportal areas. Ovariectomy decreased ER level (from 10.2 +/- 3.2 to 4.3 +/-
      1.3) and ER mRNA expression (from 12.8 +/- 2.1 to 10.9 +/- 1.3) significantly
      (P<0.05). Hepatic ER and ER mRNA concentrations were elevated after treatment
      with estradiol in both ovariectomy (15.8 +/- 2.4, 20.8 +/- 3.1) and sham
      ovariectomy (18.7 +/- 3.8, 23.1 +/- 3.7) fibrotic groups (P<0.05). CONCLUSION:
      The increase in hepatic ER and mRNA expression may be part of the molecular
      mechanisms underlying the suppressive effect of estradiol on liver fibrosis
      induced by CCl4 administration.

PMID- 14716834
TI  - Expression of liver insulin-like growth factor 1 gene and its serum level in
      patients with diabetes.
AB  - AIM: To explore the effect of diabetic duration and blood glucose level on
      insulin like growth factor 1 (IGF-1) gene expression and serum IGF-1 level.
      METHODS: Diabetes was induced into Sprague Dawley rats by alloxan and then the
      rats were subdivided into different groups with varying blood glucose level and
      diabetic duration. The parameters were measured as follows: IGF-1 mRNA by reverse
      transcriptase-polymerase chain reaction (RT-PCR), IGF-1 peptide and serum IGF-1
      concentration by enzyme-linked immunosorbent assay (ELISA). RESULTS: During early
      diabetic stage (week 2), in comparison with normal control group (NC), IGF-1 mRNA
      (1.17 +/- 0.069 vs 0.79 +/- 0.048, P<0.001; 1.17 +/- 0.069 vs 0.53 +/- 0.023,
      P<0.0005, respectively), IGF-1 peptide contents [(196.66 +/- 14.9) ng/mg(-1) vs
      (128.2 +/- 11.25) ng/mg(-1), P<0.0005; (196.66 +/- 14.9) ng/mg(-1) vs (74.43 +/-
      5.33) ng/mg(-1), P<0.0001, respectively] were reduced in liver tissues of
      diabetic rats. The IGF-1 gene downregulation varied with glucose control level of
      the diabetic state, and deteriorated gradually further with duration of diabetes.
      By month 6, hepatic tissue IGF-1mRNA was 0.71 +/- 0.024 vs 1.12 +/- 0.056,
      P<0.001; 0.47 +/- 0.021 vs 1.12 +/- 0.056, P<0.0005, respectively. IGF-1 peptide
      was (114.35 +/- 8.09) ng/mg(-1) vs (202.05 +/- 15.73) ng/mg(-1), P<0.0005; (64.58
      +/- 3.89) ng/mg(-1) vs (202.05 +/- 15.73) ng/mg(-1), P<0.0001 respectively. Serum
      IGF-1 was also lowered in diabetic group with poor control of blood glucose. On
      week 2, serum IGF-1 concentrations were (371.0 +/- 12.5) ng/mg(-1) vs (511.2 +/-
      24.7) ng/mg(-1), P<0.0005, (223.2 +/- 9.39) ng/mg(-1) vs (511.2 +/- 24.7) ng/mg(
      1), P<0.0001 respectively. By month 6, (349.6 +/- 18.62) ng/mg(-1) vs (520.7 +/-
      26.32) ng/mg(-1), P<0.0005, (188.5 +/- 17.35 vs 520.7 +/- 26.32) ng/mg(-1),
      P<0.0001, respectively. Serum IGF-1 peptide change was significantly correlated
      with that in liver tissue (r=0.99, P<0.001). Furthermore, no difference was found
      in the above parameters between diabetic rats with euglycemia and non-diabetic
      control group. CONCLUSION: The influence of diabetic status on IGF-1 gene
      expression in liver tissues is started from early diabetic stage, causing down
      regulation of IGF-1 expression, and progresses with the severity and duration of
      diabetic state. Accordingly serum IGF-1 level decreases. This might indicate that
      liver tissue IGF-1 gene expression is greatly affected in diabetes, thus
      contributing to reduction of serum IGF-1 level.

PMID- 14716835
TI  - Long-term persistence of T cell memory to HBsAg after hepatitis B vaccination.
AB  - AIM: To determine if the T cell memory to HBsAg can persist for a long time after
      hepatitis B (HB) vaccination. METHODS: Thirty one vaccine recipients who were
      healthcare workers (18 females and 13 males aged 34-58 years) from Utrecht
      University Hospital, Netherlands, and had previously received a standard course
      of vaccination for hepatitis B were investigated and another 9 unvaccinated
      healthy volunteers from the same hospital were used as the control. Blood samples
      were taken just before the experiment to test serum anti-HBs levels and the
      subjects were classified into different groups according to their serum titers of
      anti-HBs and vaccination history. Their peripheral blood mononuclear cells (PBMC)
      were isolated from freshly heparinized venous blood and the proliferative
      response of T lymphocytes to the recombinant hepatitis B surface antigen (HBsAg)
      was investigated. RESULTS: Positive serum anti-HBs was found in 61.3% (19/31)
      vaccine recipients and a significant in vitro lymphocyte proliferative response
      to recombinant HBsAg was observed in all the vaccinees with positive anti-HBs.
      Serum anti-HBs level < or =10 IU/L was found in 38.7% (12/31) subjects. In this
      study, we specially focused on lymphocyte proliferative response to recombinant
      HBsAg in those vaccine recipients with serum anti-HBsAg less than 10 IU/L. Most
      of them had received a standard course of vaccination about 10 years before. T
      lymphocyte proliferative response was found positive in 7 of the 12 vaccine
      recipients. These results confirmed that HBsAg-specific memory T cells remained
      detectable in the circulation for a long time after vaccination, even when serum
      anti-HBs level had been undetectable. CONCLUSION: The T cell memory to HBsAg can
      persist for at least 10 years after HB vaccination. Further booster injection is
      not necessary in healthy responders to HB vaccine.

PMID- 14716836
TI  - Establishment of transgenic mice carrying gene encoding human zinc finger protein
      191.
AB  - AIM: Human zinc finger protein 191 (ZNF191) was cloned and characterized as a
      Kruppel-like transcription factor, which might be relevant to many diseases such
      as liver cancer, neuropsychiatric and cardiovascular diseases. Although progress
      has been made recently, the biological function of ZNF191 remains largely
      unidentified. The aim of this study was to establish a ZNF 191 transgenic mouse
      model, which would promote the functional study of ZNF191. METHODS: Transgene
      fragments were microinjected into fertilized eggs of mice. The manipulated
      embryos were transferred into the oviducts of pseudo-pregnant female mice. The
      offsprings were identified by PCR and Southern blot analysis. ZNF 191 gene
      expression was analyzed by RT-PCR. Transgenic founder mice were used to establish
      transgenic mouse lineages. The first generation (F1) and the second generation
      (F2) mice were identified by PCR analysis. Ten-week transgenic mice were used for
      pathological examination. RESULTS: Four mice were identified as carrying copies
      of ZNF191 gene. The results of RT-PCR showed that ZNF 191 gene was expressed in
      the liver, testis and brain in one of the transgenic mouse lineages. Genetic
      analysis of transgenic mice demonstrated that ZNF 191 gene was integrated into
      the chromosome at a single site and could be transmitted stably. Pathological
      analysis showed that the expression of ZNF 191 did not cause obvious pathological
      changes in multiple tissues of transgenic mice. CONCLUSION: ZNF 191 transgenic
      mouse model would facilitate the investigation of biological functions of ZNF191
      in vivo.

PMID- 14716837
TI  - Effects of depression on parameters of cell-mediated immunity in patients with
      digestive tract cancers.
AB  - AIM: To evaluate the effects of depression on parameters of cell-mediated
      immunity in patients with cancers of the digestive tract. METHODS: One hundred
      and eight adult patients of both sexes with cancers of the digestive tract
      admitted between March 2001 and February 2002 in the Department of Medical
      Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly
      enrolled in the study. The Zung self-rating depression scale (SDS), Zung self
      rating anxiety scale (SAS), numeric rating scale (NRS) and social support rating
      scale (SSRS) were employed to evaluate the degree of depression and their
      contributing factors. In terms of their SDS index scores, the patients were
      categorized into depression group (SDS> or =50) and non-depression group
      (SDS<50). Immunological parameters such as T-lymphocyte subsets and natural
      killer (NK) cell activities in peripheral blood were determined and compared
      between the two groups of patients. RESULTS: The SDS index was from 33.8 to 66.2
      in the 108 cases, 50% of these patients had a SDS index more than 50. Similarly,
      the SAS index of all the patients ranged from 35.0 to 62.0 and 46.3% of the cases
      had a SAS index above 50. Cubic curve estimation showed that the depression was
      positively correlated with anxiety and negatively with social support.
      Furthermore, the depression correlated with the tumor type, which manifested in a
      descending order as stomach, gallbladder, pancreas, intestine, esophagus,
      duodenum and rectum, according to their correlativity. Step-wise regression
      analysis suggested that hyposexuality, dispiritment, agitation, palpitation, low
      CD56 and anxiety were the significant factors contributing to depression. More
      severe anxiety (49.7 +/- 7.5 vs 45.3 +/- 6.9, P<0.05), pain (6.5 +/- 2.8 vs 4.6
      +/- 3.2, P<0.05), poor social support (6.8 +/- 2.0 vs 7.6 +/- 2.1, P<0.05), as
      well as decline of lymphocyte count (0.33 +/- 0.09 vs 0.39 +/- 0.87, P<0.05) and
      CD56 (0.26 +/- 0.11 vs 0.29 +/- 0.11, P<0.05) were noted in the depression group
      compared with those of the non-depression patients. However, fewer obvious
      changes in CD4/CD8 ratio and other immunological parameters were found between
      the two groups. CONCLUSION: Depression occurs with a high incidence in patients
      with cancers of the digestive tract, which probably is not the sole factor
      leading to the impairment of immunological functions in these cases. However,
      comprehensive measures including psychological support should be taken in order
      to improve the immunological function, quality of life and clinical prognosis of
      these patients.

PMID- 14716838
TI  - Estimating medical costs of gastroenterological diseases.
AB  - AIM: To estimate the direct medical costs of gastroenterological diseases within
      the universal health insurance program among the population of local residents in
      Taiwan. METHODS: The data sources were the first 4 cohort datasets of 200,000
      people from the National Health Insurance Research Database in Taipei. The
      ambulatory, inpatient and pharmacy claims of the cohort in 2001 were analyzed.
      Besides prevalence and medical costs of diseases, both amount and costs of
      utilization in procedures and drugs were calculated. RESULTS: Of the cohort with
      183,976 eligible people, 44.2% had ever a gastroenterological diagnosis during
      the year. The age group 20-39 years had the lowest prevalence rate (39.2%) while
      the elderly had the highest (58.4%). The prevalence rate was higher in women than
      in men (48.5% vs. 40.0%). Totally, 30.4% of 14,888 inpatients had ever a
      gastroenterological diagnosis at discharge and 18.8% of 51,359 patients at
      clinics of traditional Chinese medicine had such a diagnosis there. If only the
      principal diagnosis on each claim was considered, 16.2% of admissions, 8.0% of
      outpatient visits, and 10.1% of the total medical costs (8,469,909 US
      dollars/83,830,239 US dollars) were attributed to gastroenterological diseases.
      On average, 46.0 US dollars per insured person in a year were spent in treating
      gastroenterological diseases. Diagnostic procedures related to
      gastroenterological diseases accounted for 24.2% of the costs for all diagnostic
      procedures and 2.3% of the total medical costs. Therapeutic procedures related to
      gastroenterological diseases accounted for 4.5% of the costs for all therapeutic
      procedures and 1.3% of the total medical costs. Drugs related to
      gastroenterological diseases accounted for 7.3% of the costs for all drugs and
      1.9% of the total medical costs. CONCLUSION: Gastroenterological diseases are
      prevalent among the population of local residents in Taiwan, accounting for a
      tenth of the total medical costs. Further investigations are needed to
      differentiate costs in screening, ruling out, confirming, and treating.

PMID- 14716839
TI  - Expression of bcl-2 gene family during resection induced liver regeneration:
      comparison between hepatectomized and sham groups.
AB  - AIM: During liver regeneration cellular proliferation and apoptosis result in
      tissue remodeling to restore normal hepatic mass and structure. Main regulators
      of the apoptotic machinery are the Bcl-2 family proteins but their roles are not
      well defined throughout the liver regeneration. We aimed to analyze the
      expression levels of bcl-2 gene family members during resection induced liver
      regeneration. METHODS: We performed semi-quantitative RT-PCR to examine the
      expression level of bak, bax, bcl-2 and bcl-xL in 70% hepatectomized rat livers
      during the whole regeneration process and compared to that of the sham and normal
      groups. RESULTS: The expression of bak and bax was decreased whereas that of bcl
      2 and bcl-xL was increased in hepatectomized animals compared to normal liver at
      most time points. We also reported for the first time that sham group of animals
      had statistically significant higher expression of bak and bax than
      hepatectomized animals. In addition, the area under the curve (AUC) values of
      these genes was larger in sham groups than the hepatectomized groups. CONCLUSION:
      The expression changes of bak, bax, bcl-2 and bcl-xL genes are altered not only
      due to regeneration, but also due to effects of surgical operations.

PMID- 14716840
TI  - Complications of stent placement for benign stricture of gastrointestinal tract.
AB  - AIM: To observe the frequent complications of stent placement for stricture of
      the gastrointestinal tract and to find proper treatment. METHODS: A total number
      of 140 stents were inserted in 138 patients with benign stricture of the
      gastrointestinal tract. The procedure was completed under fluoroscopy in all of
      the patients. RESULTS: Stents were successfully placed in all the 138 patients.
      Pains occurred in 23 patients (16.7%), slight or dull pains were found in 21
      patients and severe chest pain in 2 respectively. For the former type of pain,
      the patients received only analgesia or even no treatment, while peridural
      anesthesia was conducted for the latter condition. Reflux occurred in 16 of these
      patients (11.6%) after stent placement. It was managed by common antireflux
      procedures. Gastrointestinal bleeding occurred in 13 patients (9.4%), and was
      treated by hemostat. Restenosis of the gastrointestinal tract occurred in 8
      patients (5.8%), and was apparently associated with hyperplasia of granulation
      tissue. In 2 patients, the second stent was placed under X-ray guidance. The
      granulation tissue was removed by cauterization through hot-node therapy under
      gastroscope guidance in 3 patients, and surgical reconstruction was performed in
      another 3 patients. Stent migration occurred in 5 patients (3.6%), and were
      extracted with the aid of a gastroscope. Food-bolus obstruction was encountered
      in 2 patients (1.4%) and was treated by endoscope removal. No perforation
      occurred in all patients. CONCLUSION: Frequent complications after stent
      placement for benign stricture of the gastrointestinal tract include pain,
      reflux, bleeding, restenosis, stent migration and food-bolus obstruction. They
      can be treated by drugs, the second stent placement or gastroscopic procedures
      according to the specific conditions.

PMID- 14716841
TI  - Long-term outcome of esophageal myotomy for achalasia.
AB  - AIM: Modified Heller's myotomy is still the first choice for achalasia and the
      assessment of surgical outcomes is usually made based on the subjective sensation
      of patients. This study was to objectively assess the long-term outcomes of
      esophageal myotomy for achalasia using esophageal manometry, 24-hour pH
      monitoring, esophageal scintigraphy and fiberoptic esophagoscopy. METHODS: From
      February 1979 to October 2000, 176 patients with achalasia underwent modified
      Heller's myotomy, including esophageal myotomy alone in 146 patients, myotomy in
      combination with Gallone or Dor antireflux procedure in 22 and 8 patients,
      respectively. Clinical score, pressure of the lower esophageal sphincter (LES),
      esophageal clearance rate and gastroesophageal reflux were determined before and
      1 to 22 years after surgery. RESULTS: After a median follow-up of 14 years, 84.5%
      of patients had a good or excellent relief of symptoms, and clinical scores as
      well as resting pressures of the esophageal body and LES were reduced compared
      with preoperative values (P<0.001). However, there was no significant difference
      in DeMeester score between pre- and postoperative patients (P=0.51). Esophageal
      transit was improved in postoperative patients, but still slower than that in
      normal controls. The incidence of gastroesophageal reflux in patients who
      underwent esophageal myotomy alone was 63.6% compared to 27.3% in those who
      underwent myotomy and antireflux procedure (P=0.087). Three (1.7%) patients were
      complicated with esophageal cancer after surgery. CONCLUSION: Esophageal myotomy
      for achalasia can reduce the resting pressures of the esophageal body and LES and
      improve esophageal transit and dysphagia. Myotomy in combination with antireflux
      procedure can prevent gastroesophageal reflux to a certain extent, but further
      randomized studies should be carried out to demonstrate its efficacy.

PMID- 14716842
TI  - Expression of COX-2 proteins in gastric mucosal lesions.
AB  - AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions
      and to assess the relationship between COX-2 expression and type, pathologic
      stage, differentiation, or lymph node metastasis in gastric cancer and the
      relationship between COX-2 expression and H pylori infection in gastric mucosal
      lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical
      resection. Samples were taken from tumor site and paracancerous tissues, and ABC
      immunohistochemical staining was used to detect the expression of COX-2 proteins.
      H pylori was determined by rapid urea test combined with pathological stating/14C
      urea breath test. RESULTS: The positive rate and staining intensity of mutant COX
      2 gene expression in gastric cancer were significantly higher than those in
      paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant
      correlation between COX-2 and pathologic stage or lymph node metastasis type of
      gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was
      found between COX-2 expression and type or grade of differentiation (P>0.05). COX
      2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H
      pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%,
      60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large
      proportion of gastric cancer tissues compared with matched non-cancerous tissues
      and was significantly associated with advanced tumor stage and lymph node
      metastasis. Overexpression of COX-2 plays an important role in tumor progression
      of gastric cancer. COX-2 may also play a role in the early development/promotion
      of gastric carcinoma and is associated with H pylori infection.

PMID- 14716843
TI  - Effects of Zhaoyangwan on chronic hepatitis B and posthepatic cirrhosis.
AB  - AIM: To study the therapeutic effects of zhaoyangwan (ZYW) on chronic hepatitis B
      and hepatic cirrhosis and the anti-virus, anti-fibrosis and immunoregulatory
      mechanisms of ZYW. METHODS: Fifty cases of chronic hepatitis B and posthepatic
      cirrhosis with positive serum HBsAg, HBeAg, anti-Hbc and HBV-DNA were divided
      randomly and single-blindly into the treatment group (treated with ZYW) and the
      control group (treated with interferon). After 3 month treatment, the effects of
      the treatment group and the control group were evaluated. RESULTS: The serum ALT
      normalization was 83.3% (30/36) in the treatment group and 85.7% (12/14) in the
      control group, with no significant difference (chi2=0.043, P>0.05). After the
      course, the negative expression rates of the serum HBV-DNA and HBeAg were 44.4%
      (16/36) and 50% (18/36) in the treatment group, and 50% (7/14) and 50% (7/14) in
      the control group, respectively, with no significant difference (chi2=0.125,
      chi2=0.00, both P>0.05). Negative HBsAg and positive HBsAb appeared in 4 cases of
      the treatment group and 1 case of the control group. Serum anti-HBc turned
      negative in 6 cases of the treatment group and 1 case of the control group,
      respectively. After the ZYW treatment, serum CD3+, CD4+, CD8+, CD4+/CD8+ and NK
      cell activation were significantly increased. Only serum CD3+ and NK cell
      activation were significantly increased in the control group with a significant
      difference between the two groups. The serum C4, C1q, C3, B and C9 were
      significantly increased in the treatment group. In the control group only the
      serum C4 was increased. The concentration of serum interferon had no change after
      treatment with ZYW, while it was significantly increased in the control group
      after treatment with interferon. The ultrastructure of the liver restored, which
      helped effectively to reduce the degeneration and necrosis of hepatic
      cells,infiltration of inflammatory cells and hepatic cirrhosis. CONCLUSION: ZYW
      is a pure Chinese herbal medicine. It can exert potent therapeutic effects on
      chronic hepatitis B and posthepatic cirrhosis. ZYW has similar therapeutic
      effects to those of interferon. It is cheap and easily administered with no
      obvious side-effects. It can be widely used in clinical practice.

PMID- 14716844
TI  - Enhancement of migration and invasion of hepatoma cells via a Rho GTPase
      signaling pathway.
AB  - AIM: Intrahepatic extension is the main cause of liver failure and death in
      hepatocellular carcinoma patients. The small GTPase Rho and one of its effector
      molecules ROCK regulate cytoskeleton and actomyosin contractility, and play a
      crucial role in cell adhesion and motility. We investigated the role of small
      GTPase Rho in biological behaviors of hepatocellular carcinoma to demonstrate the
      importance of Rho in cancer invasion and metastasis. METHODS: Using Western
      blotting, we quantitated Rho protein expression in SMMC-7721 cells induced by
      Lysophosphatidic acid (LPA). Furthermore, we examined the role of Rho signaling
      in regulating the motile and invasive properties of tumor cells. RESULTS: Rho
      protein expression was stimulated by LPA. Using the Rhotekin binding assay to
      assess Rho activation, we observed that the level of GTP-bound Rho was elevated
      transiently after the addition of LPA, and Y-27632 decreased the level of active
      Rho. LPA enhanced the motility of tumor cells and facilitated their invasion. Rho
      played an essential role in the migratory process, as evidenced by the inhibition
      of migration and motility of cancer cells by a specific inhibitor of ROCK, Y
      27632. CONCLUSION: The finding that invasiveness of hepatocellular carcinoma is
      facilitated by the Rho/Rho-kinase pathway is likely to be relevant to tumor
      progression and Y-27632 may be a new potential effective agent for the prevention
      of intrahepatic extension of human liver cancer.

PMID- 14716845
TI  - Determination of chemical composition of gall bladder stones: basis for treatment
      strategies in patients from Yaounde, Cameroon.
AB  - AIM: Gallstone disease is increasing in sub-saharan Africa (SSA). In the west,
      the majority of stones can be dissolved with bile salts, since the major
      component is cholesterol. This medical therapy is expensive and not readily
      accessible to poor populations of SSA. It was therefore necessary to analyze the
      chemical composition of biliary stones in a group of patients, so as to make the
      case for introducing bile salt therapy in SSA. METHODS: All patients with
      symptomatic gallstones were recruited in the study. All stones removed during
      cholecystectomy were sent to Houston for x-ray diffraction analysis. Data on age,
      sex, serum cholesterol, and the percentage by weight of cholesterol, calcium
      carbonate, and amorphous material in each stone was entered into a pre
      established proforma. Frequencies of the major components of the stones were
      determined. RESULTS: Sixteen women and ten men aged between 27 and 73 (mean 44.9)
      years provided stones for the study. The majority of patients (65.38%) had stones
      with less than 25% of cholesterol. Amorphous material made up more than 50% and
      100% of stones from 16 (61.53%) and 9 (34.61%) patients respectively. CONCLUSION:
      Cholesterol is present in small amounts in a minority of gallstones in Yaounde.
      Dissolution of gallstones with bile salts is unlikely to be successful.

PMID- 14716847
TI  - [The selection of Tikhonov regularization parameter in dynamic electrical
      impedance imaging].
AB  - Dynamic electrical impedance imaging is a non-linear inverse problem which is
      always discretized by finite element method and solved by linear model. Since the
      coefficient matrix of the linear model is ill-conditioned, the regularization
      method is used to get stable solution. However Tikhonov regularization is easy to
      realize, the selection of the regularization parameter is bothering. In this
      paper, according to the results of a great number of experiments, a new method
      for determining the regularization parameter is presented which uses the
      characteristic of the product of the norm of the error and the regularization
      solution. The reconstructed image using the regularization parameter selected by
      the proposed method has good spatial resolution.

PMID- 14716846
TI  - Can HB vaccine yield a booster effect on individuals with positive serum anti-HBs
      and anti-HBc markers?
AB  - AIM: To evaluate if HB vaccination can yield a booster effect on the anti-HBs
      level of those naturally acquired HBV positive markers. METHODS: Sera were
      collected from 1399 newly enrolled university students aged between 18-20 years
      at the entrance medical examination in 2001. Forty-four students (28 males and 16
      females) with positive serum anti-HBs and anti-HBc markers served as an
      observation group and another 44 students (24 males and 20 females) without any
      HBV markers as the control. HB vaccination was given to all the students without
      positive serum HBsAg according to 0, 1, 6 month regimen and the peripheral venous
      blood was sampled from those of both observation and control groups for anti-HBs
      detection one month after the second and third doses. Anti-HBs levels were
      measured by ELISA. RESULTS: The seroconversion rate of anti-HBs in the control
      group was 100% after the second dose, but the geometric mean titers (GMTs) were
      low. The tendency of serum anti-HBs changes after the 3rd dose was completely
      different between the two groups. Although more than half of those with positive
      anti-HBs and anti-HBc showed a mild increase of anti-HBs levels after the 2nd
      boosting dose (mean anti-HBs level was 320:198 mIU), but the increase of serum
      anti-HBs titer was much smaller than that in the control group. The averages of
      their initial serum anti-HBs levels and the levels after the 2nd and 3rd doses
      were 198, 320 and 275 mIU respectively. All the subjects from the control group
      had an obvious increase in their serum anti-HBs levels which was nearly 4 times
      the baseline level (302:78 mIU). CONCLUSION: HB vaccination can not enhance anti
      HBs levels in those with positive serum anti-HBs and anti-HBc markers.

PMID- 14716848
TI  - [The effects of backpack loading on the gait and corresponding compensatory
      strategy].
AB  - This study was designed to determine the effect of backpack loading on the gait
      pattern and corresponding compensatory strategy, which is important to the
      balance control of biped robot and military training. Five healthy subjects were
      instructed to walk at their preferred speed on level pathway taking three
      different loads i.e. 6 kg, 12 kg and 25 kg, on their backs. The results showed
      that the gait pattern was apparently influenced, and the dominant effects were
      found to be the flexion of hip, knee joints and pitch angle of torso. The stride
      speed decreased apparently with loading on their backs, but the stride length
      showed less changes. Besides, the responses to taking loads might be influenced
      by the strength of body. An apparent multi-joints coordination motor mode was
      employed to compensate the influences of loading, however, their contributions
      are different; hip, knee joints and torso pitch made dominant contributions to
      the compensation while ankle joints made minor. The anterior pitch of upper torso
      could be employed to adjust the overall center of mass while loading on their
      backs, the larger the magnitude of loading on their backs, the larger the
      anterior pitch angle of torso. After the heel touched the ground, the flexion of
      hip and knee joints were effective for the shock absorption, which means that the
      stiffness of hip and knee joints can be used to absorb the shock and avoid the
      trauma of each joints.

PMID- 14716849
TI  - [Biomechanical properties of skin expanded by different methods in vivo].
AB  - In plastic surgery, people hope the conventional expansion will be replaced by
      rapid expansion, which can shorten greatly the expansion period. Also people are
      concerned about whether the skin properties after rapid expansion approach that
      after conventional expansion. So we designed and made an apparatus for in vivo
      measurement of tension, and then measured the biomechanical properties of skin in
      vivo for the first time. The experimental results showed there was no significant
      difference between the rapid expansion method and conventional expansion method
      in respect to the area gain of expanded skin surface. Both the tension in vivo
      and the instant stretch-back ratio increased during the expansion, but fell
      almost to the control values after four weeks' maintaining period. So, rapid skin
      expansion did not produce any deleterious effect when compared with the
      conventional expansion. Extension of the maintaining period can improve the
      biomechanical properties of expanded skin and effectively reduce the stretch-back
      ratio. Therefore, rapid expansion with an extended maintaining period is
      clinically acceptable.

PMID- 14716850
TI  - [Improve wear resistance of UHMWPE by O+ ion implanted].
AB  - Ultra high molecular weight polyethylene (UHMWPE) was implanted with 450 keV and
      100 keV O+ ions at dosage of 1 x 10(15)/cm2, 5 x 10(15)/cm2, 3 x 10(14)/cm2,
      respectively. Its wear behaviors were studied under dry friction condition and
      lubrication by means of distilled water using a pin-on-disk tribometer with a
      Si3N4 ceramic ball as a counterface. The wear surfaces were examined with SEM.
      The experimental results showed that the wear rate of implanted UHMWPE is lower
      than that of un-implanted UHMWPE under both dry and distilled friction
      conditions, especially for 450 keV energy and 5 x 10(15)/cm2 dose implantation.
      The friction coefficient of O+ ions implanted UHMWPE is higher than that of un
      implanted UHMWPE under both dry and distilled friction conditions. The adhesive,
      plow and plastic deformation are the wearing mechanism for un-implanted UHMWPE;
      the fatigue and abrasive wear are that for implanted UHMWPE.

PMID- 14716851
TI  - [In vitro release of tetracycline hydrochloride from alpha-TCP cement].
AB  - Drug release from alpha-TCP cement containing tetracycline hydrochloride (TTCH)
      was studied in vitro. Results from X-ray diffraction study indicated that TTCH
      did not prevent the hydration of alpha-TCP. In vitro drug release study showed
      that TTCH release could sustain over 1200 h, and the release was controlled by
      two mechanisms: (1) diffusion of free TTCH molecules through the porous cement
      (square-root-of-time kinetics); (2) dissociation of TTCH from the apatite-TTCH
      complex (zero-order kinetics). The mechanism controlling release would changed
      with the variety of the antibiotic content of cement pellets, as a result of TTCH
      adsorption and bonding on calcium phosphates. The first mechanism was
      predominantly for low concentration system TTCH-loaded apatite cement systems at
      the initial release period, and for high concentration TTCH-loaded apatite cement
      systems. As for low concentration TTCH-loaded apatite cement systems at later
      release stage, drug release was controlled by the coupling of the two mechanisms.

PMID- 14716852
TI  - [Study on injectable bioactive bone repairing material of nano-hydroxyapatite and
      polyamide-66 composite].
AB  - The aim of this study was to evaluate the injectability, histocompatibility,
      function and other properties of the injectable bioactive bone repairing material
      of nano-hydroxyapatite and polyamide-66 (n-HA/PA66) composite. The XRD pattern,
      the relationship between the injectability and liquid-powder ratio, setting time
      and liquid-powder ratio, compressive strength and liquid-powder ratio were
      assessed. The size of the composite was determined to be 70 nm in length and 30
      to 50 nm in width, and the molecular weight of polyamides-66 was 18000. The
      diameter of pores of the composite was about 200 to 400 micrometer. To evaluate
      the histocompatibility and function, 8 male dogs were studied with the injectable
      n-HA/PA66 composite implanted in the artificial defected alveolus of mandible on
      only one side to be compared with the intact alveolus on the other side. The
      specimens were taken at 4, 8, 12, 16 months after the implantation and the
      results were evaluated. The XRD pattern of the solidificated n-HA/PA66 composite
      was the same as the powdered n-HA/PA66 composite. The injectable n-HA/PA66
      composite had a good injectability, 25 to 30 minutes setting time and about 37
      MPa compressive strength when the liquid-powder ratio was 0.50. The healing of
      the gingiva was well at the implanted areas in all animals. The height of the
      repaired alveolar bone was obvious higher than that of the blank control. The
      earlier sign of ossification was histologically observed at 16 weeks after
      implantation. The injectable n-HA/PA66 composite has good biocompatibility and
      osteoconductive property. As an injectable material, with good maneuverability,
      it is useful for repairing irregular bone defects, especially in oral and
      maxillofacial surgery.

PMID- 14716853
TI  - [The quantity analysis of reverse transcriptase in porcine endogenous retrovirus
      expressed in Banna minipig inbred].
AB  - Quantitative RT(reverse transcriptase) assay was established to detect the
      reverse transcriptase in plasma of thirty-four Chinese Banna minipig inbred in
      this work. The protocol was given in the RT kit (Roche), using HIV-1 as the
      positive control of the kit and supernatant of PK-15 as the PERV positive control
      respectively. The results show that positive reverse transcriptase reaction can
      be detected in the plasma of the pigs, but the levels are much lower than that of
      HIV-1 and lower than that of PERV in supernatant of PK-15.

PMID- 14716854
TI  - [Overexpression of TGF beta 1 increases elastin expression and adhesion of smooth
      muscle cells].
AB  - This study was conducted to examine the effectiveness of a gene transfer of human
      TGF beta 1 gene into smooth muscle cells and whether the TGF beta 1 can increase
      elastin expression of smooth muscle cells. With the help of DOTAP, smooth muscle
      cells were transfected with pMAMneoTGF beta 1. The positive cell clones were
      selected with G418. The stable transfection and expression of TGF beta 1 in the
      smooth muscle cells were determined by immunofluorescence analysis. The
      expression of elastin in the transfected and untransfected cells were determined
      by in situ hybridization. The adhesion force between smooth muscle cells and
      matrix was detected by micropipette system. The results showed abundant TGF beta
      1 stable expression in smooth muscle cells. TGF beta 1 gene can increase two
      three times elastin expression and increase the adhesion between smooth muscle
      cells and matrix. TGF beta 1 can be used in vascular tissue engineering to
      increase smooth muscle cells adhesion.

PMID- 14716855
TI  - [Biomechanical properties of tissue-engineered tendons after repairing digital
      flexor tendons in chickens].
AB  - Experiments have been performed to investigate why the biomechanical strength of
      repaired tendons is lower than that of the normal tendon when the engineered
      tendons are implanted in vivo to replace the tendon defects. We seeded the
      primary culture tendon cells derived from Roman chickens' digital flexor tendons
      on the degradable polyglycolic acid meshes to construct tissue-engineered
      tendons. The flexor tendon defects (0.5 cm-0.8 cm) excised in second digit
      bilaterally in 20 Roman chickens, had been repaired with the constructed tissue
      engineered tendons. The samples of repaired tendons were collected at 2, 4, 6 and
      8 weeks after operation. Tests for scaffold weight, hydroxyproline content, and
      mechanical strength of the samples were performed. We found that from 2 weeks to
      8 weeks afteroperation, the weight of the scaffolds decreased significantly,
      almost disappearing at 8 weeks; the hydroxyproline content determining the total
      collagen content increased gradually without significance; mechanically, both
      energy at break and tensile strength showed a tendency of drastic decrease at
      first 4 weeks afteroperation and a gradual increase afterwards, but the tensile
      strength at 8 weeks afteroperation was only 23% of that of the normal tendon. We
      conclude that the lower biomechanical strength of repaired tendons is owing to
      the serious mismatch between scaffold degradation and collagen synthesis.

PMID- 14716856
TI  - [Effect of impeller vane number and angles on pump hemolysis].
AB  - To evaluate the effect of impeller design on pump hemolysis, five impellers with
      different number of vanes or different vane angles were manufactured and tested
      in one pump for hemolysis comparison. The impellers are made to have the same
      dimension and same logarithmic spiral vane from which coincide with the stream
      surfaces in the pump, according to the analytical and three-dimensional design
      method developed by the authors. Consequently, an impeller with 6 vanes and 30
      degrees vane angle has the lowest hemolysis index. This result agrees with the
      theoretical analyses of other investigators searching optimal number of vanes and
      vane angle to achieve the highest efficiency of the pump.

PMID- 14716857
TI  - [Experimental study in vitro on toxicology and cytocompatibility of
      collagen/hydroxylapatite (CHA) composite material as part of tracheal
      prosthesis].
AB  - Cytotoxicity and cytocompatibility remains the principal theme for biomaterials
      application in medicine. The purpose of this study was to investigate the
      cytotoxicity and cytocompatibility of collagen/hydroxyapatite(CHA) composite
      material in vitro in order to provide useful scientific basis for clinical use.
      Cellular cultivation in vitro and MTT assay were conducted for evaluating the
      composite material's influence on the morphology, growth and proliferation of
      cultured cell(L-929 cell). The hemolysis test was also performed for evaluating
      the impact on the function and metabolism of erythrocyte. These results
      demonstrated that the CHA composite material had no cytotoxicity and no hemolytic
      effect, and it might not be harmful to the morphology of the L-929 cell. The
      growth and proliferation of the L-929 cell could not be inhibited significantly.
      The cytotoxicity score of the composite material was grade 0. The hemolysis rate
      was 1.85%. In conclusion, collagen/hydroxyapatite (CHA) composite material might
      have good cytocompatibility and be safe for clinical use.

PMID- 14716858
TI  - [Study of high-intensity electric pulse inhibited sarcoma for improving antitumor
      drug effect].
AB  - This article reports the experiment studies on treating the S-180 sarcomas of KM
      mice with high-intensity electric pulse and antitumor drug (cyclophosphamide).
      The results showed that the experimental group of electric field combined with
      drug has the best effect on tumor, compared with the control group. In addition,
      electric field can inhibit the formation of vas Capillaries and decrease the
      supply of nutrition for tumor cell. In conclusion, electric field has inhibited
      the growth of tumor.

PMID- 14716859
TI  - [Noninvasive continuous measurement of blood glucose concentration via animal
      skin].
AB  - In this study we deliberated over the principles and methods and then took the
      noninvasive continuous measurement of blood glucose concentration through the
      skin of rabbits. The glucose oxidase sensor was made by covalent immobilization.
      The best making method of sensor and stable working condition were sifted. Ten
      female and 10 male adult white rabbits were allocated into the groups of the ante
      ultrasound and post-ultrasound, the injection of glucose, and the high and low
      frequency ultrasounds. After the skin surface was treated by high or low
      frenquency ultrasound for 5 minutes on the rabbits, obvious changes (P < 0.01) of
      post-ultrasound and post-injection of glucose were observed by means of glucose
      oxidase sensor and microcurrent apparatus. After application of ultrasound to the
      skin of rabbits, the penetration of glucose through the rabbit skin increased
      obviously. The change of microcurrent signal that was exchanged by the glucose
      sensor correlated positively with the concentration of glucose of rabbit body.
      The blood glucose can be tested by the glucose sensor on the skin surface of
      living animal.

PMID- 14716860
TI  - [Morphologic features of the acetabulum bone joint area].
AB  - The research on the morphology features of the acetabulum bone joint surface area
      would be helpful to establishing the acetabulum 3D model for the purpose of the
      biomechanical analysis of hip joint, and therefore might have its important
      clinical significance. However, in former studies, the acetabulum was simply
      considered as a semi sphere. In this study, based on the acetabulum 3D-point data
      acquired by the 3D laser surface scanner and the reverse engineering technology
      together with the optimal fit algorithm, two kinds of best-fit model were
      achieved by a sphere surface and a rotating elliptical surface respectively
      approaching to the acetabulum bone joint surface. Both fitting errors were then
      compared and analyzed. The results showed that the fitting error of the rotating
      elliptical surface was significantly less than that of the sphere surface (P <
      0.001). The average radius of fitting sphere was 24.37 +/- 2.22 mm and the
      average long axis of fitting rotating elliptical surface was 26.02 +/- 2.76 mm
      while its short axis was 24.17 +/- 2.16 mm. These findings would be helpful to
      our new recognition of the acetabulum since they were results of the first
      quantitative analyses for the acetabulum bone surface and also might serve as an
      important reference base in its further studies and application.

PMID- 14716861
TI  - [The 3D finite element stress analysis of transtibial monolimb].
AB  - In this study, a 3D model of a transtibial monolimb and residual limb was
      constructed. The stresses on all nodes of the model under the simulus of the load
      at the Mid-Stance were computed through 3D finite element analysis (FEA). The
      stress distribution on the internal and external surfaces of the model was
      obtained. The results indicate that the stresses on socket are lower than those
      on prosthetic shank; high stress regions are located on the underneath of
      prosthetic shank and the border section of socket and prosthetic shank. These
      data will be useful for CAD?CAM system of monolimb designing.

PMID- 14716862
TI  - [Experimental study of controlled release microencapsulated Salmonella typhi
      capsular polysaccharide vaccines immunized mice].
AB  - Salmonella Typhi capsular polysaccharide vaccines were encapsulated in the Micro
      particles made from polyethylene glycol-poly-DL-lactide (PELA). BALB/c mouse were
      divided into three groups with 20 mice in each. Mouse were immunized respectively
      with controlled release microencapsulated Salmonella Typhi capsular
      polysaccharide vaccines and Salmonella Typhi capsular polysaccharide vaccines by
      oral and subcutaneous administration. The mice blood and salvia were collected at
      the 2nd, 4th and 8th weeks respectively for the titrating of IgG and sIgA
      antibodies by RIA. At the 8th week, live typhoid bacteria were injected into the
      immunized mice for the calculation of the rate of immunization protection. The
      IgG titers of the controlled release microencapsulated Salmonella Typhi capsular
      polysaccharide vaccines group were higher than those of the other groups(P <
      0.05). The IgA titers of the low groups of controlled release microencapsulated
      Salmonella Typhi capsular polysaccharide vaccines (oral and subcutaneous) were
      higher than those of the group of Salmonella Typhi capsular polysaccharide
      vaccines (P < 0.05). The immunization protection rates of the three groups were
      40%, 100% and 60% respectively. The controlled release microencapsulated
      Salmonella Typhi capsular polysaccharide vaccines possess the advantages of
      releasing slowly in vivo and persisting long time immunogenicity.

PMID- 14716863
TI  - [Preparation of a biphasic calcined bone of beta-TCP/HAP and its application in
      BMP-2 gene medicine].
AB  - In this study, we produced a biphasic absorbable calcined bone (CB) of beta
      TCP/HAP, and evaluated its function as a carrier of bone marrow derived
      mesenchymal stem cells(BMSCs) in BMP-2 gene medicine. Biphasic CB was
      manufactured and its surface was coated by collagen. X-ray diffraction analysis,
      scanning electron microscopy and biomechanical measurement were performed on the
      product. Heterotopic bone induction of product as carrier of BMP-2 gene
      transferred BMSCs and its biodegradability were tested in nude mice and goats. X
      ray diffraction analysis showed biphasic patterns of HAP and beta-TCP. Scanning
      electron microscopy showed the porosity were similar to those of the cancellous
      bone, and the adhesion of cells on the CB surface were better after surface
      coating with collagen. It had certain biomechanical strength and appropriate
      biodegradability. Biphasic CB loaded with Adv-hBMP-2 transduced BMSCs could
      induce much bony callus at the subcutaneous site of nude mice and the tibial bone
      defects of goats. The results showed biphasic CB is a superior carrier of cells
      in BMP-2 gene medicine.

PMID- 14716864
TI  - [E. coli-based production of recombinant FALL-39].
AB  - This study was aimed at constructing a prokaryotic expression system to resolve
      the difficulties in acquiring antibacterial peptide and to meet the needs of
      research and drug development. Total RNA was extracted from human pulmonary gland
      epithelial cell line SPC-A-1, and a cDNA encoding mature FALL-39 peptide was
      amplified by RT-PCR. The recombinant prokaryotic expression vector pGEX-1 lambda
      T-FALL-39 was constructed. Using affinity chromatography, thrombin cleaving and
      AU-PAGE elution, we obtained the purified FALL-39. MIC, MEC, MBC analyses
      demonstrated that the FALL-39 had strong antibacterial activity.

PMID- 14716865
TI  - [Effect of turbulent flow on adhesion molecules expression of vascular
      endothelial cells].
AB  - Mechanical environment seems to be one of the most important surviving
      environment for vessel conduit and vascular endothelial cells(ECs), while
      adhesion is one of the most important physical characteristics of ECs. In this
      study, Flow chambers of steady laminar and turbulent flow are made and improved.
      Different flow-derived VCAM-1, ICAM-1 expressions are detected by laser confocal
      microscope. Spacial and temporal curves of the adhesion molecules are protracted.
      In laminar flow, expression of VCAM-1 is dramatically elevated, whereas the
      expression of ICAM-1 is transiently elevated and it immediately falls back to the
      baseline. In turbulent flow, expression of VCAM-1 declines, while expression of
      ICAM-1 slowly rises to a peak. These results indicate that such pathological flow
      field as turbulence exerts different influence on the adhesion of vascular ECs
      from laminar flow, and turbulence could be one of the most important reasons of
      the ECs structural and functional lesion.

PMID- 14716866
TI  - [Study on combined implantation of pig dermis and autologous skin in rats].
AB  - In this study the treatment effect of combined implantation of autologous skin on
      pig dermis in injured rats was observed. Twenty-one Wistar rats were used, and
      the wounds were formed by excising a piece of full thickness skin on the back.
      After the pig dermis was implanted, the autologous skin was grafted on the dermis
      at 0.7 and 10 days. In the group with perforated pig dermis, the autograft skin
      was implanted on the day when the pig dermis was implanted. The healing effect
      was evaluated by measuring wound area, and by observing the growth of the
      autograft skin. Two weeks after the autograft skin was implanted, the skin
      securely adhered to the dermis, and the edge of autograft skin expanded clearly.
      The wound of the autograft skin implanted in the perforation of the dermis healed
      completely after 3 weeks, but the other 3 groups had remnant small wound. The
      autograft skin merged with the dermis and its surrounding tissue, but a clear
      dividing line still existed between autograft skin and dermis after implantation.
      The area of the implanted dermis and autograft skin varied from 51.8% to 65.9%
      compared to its original size. The results suggested that the time and the way of
      autologous skin grafting on xenogenous dermis may influence wound contraction and
      healing time.

PMID- 14716867
TI  - [Pingyangmycin gelatin microspheres: preparation and drug release
      characteristics].
AB  - Pingyangmycin gelatin microspheres(PYM-GMS) was prepared by optimal double-phase
      emulsified condensation polymerization for the interventional Chemoembolization
      with carotid artery therapy, and its release characteristics were studied in vivo
      and in vitro. The results of three ways of administration(vein drop, artery
      perfusion and artery embolization) were compared. The experiment indicates that
      the diameter of PYM-GMS is more appropriate for the application in external
      carotid artery embolization with PYM-GMS, which significantly reduces the
      circulating drug level and the dosage, prolongs the time period of higher drug
      concentration, achieves the purpose of sustained release and targeted tumor
      therapy.

PMID- 14716868
TI  - [Adsorption of chondroitin sulfate-A to the surface of titanium].
AB  - To elucidate the adsorption mechanism of CS-A to the surface of titanium, 5 ml
      solutions of the CS-A were reacted with 2 g of native and 2 g of calcium-treated
      titanium powder for 48 h at 37 degrees C. Residual CS-A was detected by the
      carbazole elaborate method. The results showed that no CS-A attached to native
      titanium. Comparatively, titanium treated with calcium produced a significant
      adsorption of CS-A. At concentration of 60 micrograms/ml, the adsorption of CA-A
      to calcium-treated titanium powder attained the maximum, 83 micrograms/g. Only
      EDTA can liberate the bound CS-A from titanium surface. These findings suggest
      that calcium ion is necessary for the adsorption of CS-A to titanium.

PMID- 14716869
TI  - [Basic study of dopamine transporter imaging with 131I-beta-CIT].
AB  - beta-CIT was labeled with 131I by the peracetic acid method. Cat model of
      Parkinsonism was set up with MPTP. Each of normal and PD model cats was given an
      injection of 74 MBq/0.5 ml 131I-beta-CIT into the femur vein. Then the blood
      samples were obtained at 4 h and 20 h, the radioactivity was counted with
      calibrator. The biodistribution data of 131I-beta-CIT in cat body was calculated
      (ID%/g). The cats were subjected to imaging at 0.5 h, 1 h, 2 h, 4 h, 20 h after
      the administration of radiopharmaceutical. The radioactivity in striatum and
      cerebellum was measured and striatal specific binding ratios were calculated. The
      Results showed that the radio chemical purity of 131I-beta-CIT was 97.62% +/-
      0.31%. The 131I-beta-CIT remained stable for at least 4 h after incubation with
      water and serum respectively. Following intravenous administration in cats, 131I
      beta-CIT showed high accumulation in striatum. The study of imaging in cats
      showed that striatal specific uptake of 131I-beta-CIT at 20 h after injection was
      4.83 +/- 0.82 in normal cats and 2.92 +/- 0.66 in PD cats. There was a
      significant reduction of striatal tracer uptake in PD cats, compared to the
      controls. The results of biodistribution study was in agreement with the results
      of imaging study. These results suggest that beta-CIT is an ideal agent for
      dopamine transporter imaging and can be used for the diagnosis of Parkinson's
      disease.

PMID- 14716870
TI  - [Method and apparatus for blood flow detection based on detention catheter].
AB  - The methods for measurement of blood flow contain dilution, electro-magnetism,
      nuclear magnetic resonance, Doppler etc. The dilution, which includes heat
      dilution, 131Xe, etc., can not display the moving blood flow in real-time. The
      expenses of nuclear magnetic resonance expenses are very high. Electromagnetism
      must be used in the surgical operation. And ultrasound Doppler can not record
      other parameters of hemodynamics synchronously. This paper brings up a kind of
      blood flow measuring method with simple operating rules, dependable performance,
      and low cost to meet the needs in hemodynamic studies. The differential pressure
      between stay and fluxion points of the tube is produced in proportion to the
      square of velocity while fluid flows through the tube. We not only measure blood
      pressure or transfer drug using the detention catheter with double chamber, but
      also detect the differential pressure related within blood flow. The result of
      detecting cerebral blood flow (CBF) in clinical setting shows this method can
      record the diagram of dynamic blood flow and is a valid was of detecting blood
      flow for hemodynamic studies.

PMID- 14716871
TI  - [Study on relative bioavailability of aspirin in afenca tablet].
AB  - Salicylic acid is a kind of active metabolite of aspirin in vivo. In this study,
      its concentration in plasma was detected by RP-HPLC after twenty four healthy
      male volunteers were given each a single dose of oral Afenca test and reference
      preparations. The experiment data were calculated with 3P97 program. The results
      were analyzed by ANOVA and two- and one-sided t tests. The relative
      bioavailability of salicylic acid was 105.36% +/- 14.15%; AUC0-T of salicylic
      acid of test and reference preparations were 103.10 +/- 11.92 micrograms.h/ml and
      98.45 +/- 13.49 micrograms.h/ml respectively; Tmax were 1.5 +/- 0.5 h and 1.5 +/-
      0.5 h; Cmax were 19.31 +/- 2.47 micrograms/ml and 18.95 +/- 2.49 micrograms/ml.
      Bioequivalent evaluation of two preparations by analyzing with two- and one-sided
      t tests showed that the two preparations were bioequivalent on the basis of
      salicylic acid (t1 > or = t1-0.05(22), t2 > or = t1-0.06(22)).

PMID- 14716872
TI  - [Study on infiltration glass for machinable-infiltrated-ceramic and on its
      colorants].
AB  - In order to develop tinted infiltration glass and its colorants, which can make
      the ceramic have good spectrum transmittance, color space, color stability and be
      suitable for clinical use, we selected the best prescription and confirm the
      ingredient and content of the colorants. Molten glass was prepared in Al2O3
      crucible by heating the components to 1420 degrees C for 2 hours. The refractive
      index and thermal stability of the glass were investigated. The refractive index
      of the MIC infiltration glass was 1.5969(587.6 nm, nd). It was close to the index
      of aluminous matrix 1.759(546.07 nm, ne), which increased the spectrum
      transmittance of MIC. The thermal expansion coefficient of the glass was 7.565
      microns/m/degree C, which was compatible with the thermal expansion coefficient
      of aluminous matrix(8.214 microns/m/degree C). This study proved that the tinted
      infiltration glass has good color stability, spectrum transmittance, and thermal
      expansion properties.

PMID- 14716873
TI  - [A noninvasive method for measuring and evaluating cardiac reserve of athletes].
AB  - Phonocardiogram exercise testing(PCGET) is a recently developed method for
      evaluating cardiac contractility and the cardiac reserve of patients with heart
      disease and of healthy subjects. In order to test the reliability of PCGET method
      in physical sport, the present author conducted a clinical study. The ratio of
      the amplitude of the first heart sound after PCGET to that recorded at rest was
      defined as an indicator, i.e. cardiac contractility reserve index (CCRI). PCGET
      was performed on 30 athletes and 30 non-athletes. The results showed that the
      average of CCRI was 10.139 +/- 2.631 in 30 athletes and 6.612 +/- 3.104 in 30 non
      athletes. There was a significant difference between CCRI of the two groups (P <
      0.01). Thus, PCGET might be a noninvasive, convenient and inexpensive technique
      to evaluate the cardiac reserve quantitatively for athletes.

PMID- 14716874
TI  - [Construction of recombinant caspases-3 gene and the test of its apoptotic
      activity in pancreatic carcinoma cell strain].
AB  - To explore the new gene therapeutic method for pancreatic carcinoma, the
      recombinant Caspases-3 gene (r-Caspases-3) was constructed by molecular biologic
      method. The eukaryotic expression plasmid pcDNA 3.1 (+)/r-Caspase-3 was
      constructed by rearrangement of the large subunit and small subunit of caspases
      3, and then it was transfected into pancreatic carcinoma cells strain (PC-II).
      After being transfected, the expression of r-Caspase-3 mRNA in pancreatic
      carcinoma cells was detected by RT-PCR and its apoptotic activity was detected by
      FCM. The sequencing of the recombinant molecules (r-Caspases-3) confirmed that
      its small subunit preceded its large subunit. After the pancreatic carcinoma
      cells were transfected with the pcDNA3.1(+)/r-Caspases-3 by liposomes, an 894 bp
      strap was observed by means of RT-PCR. No strap was found in control groups. A
      transparent hypodiploid karyotype peak was revealed by FCM. The above data
      indicate that the gene of r-Caspase-3 has been constructed successfully, r
      Caspase-3 has apoptotic activity and can be used as target gene in gene therapy
      for pancreatic carcinoma.

PMID- 14716875
TI  - [Study of ultrasound attenuation during HIFU propagation in ox liver].
AB  - Ultrasound attenuation has been measured during HIFU propagation in fresh ox
      liver at different frequency using a radiation force method. The acoustic
      radiation force was measured before and after the prepared ox liver of various
      thicknesses (20 mm, 40 mm, 60 mm, 80 mm) which were put into degassed water and
      exposed to different transducer surface output acoustic powers at a room
      temperature (20 degrees C) with therapeutic transducers of various frequencies,
      and then the ultrasound attenuation coefficient was calculated. With the use of
      therapeutic transducer 4, the focus of the ultrasonic beam was set to be 20 mm,
      40 mm or 60 mm deep into the tissue surface using B-mode ultrasound guidance. A
      single exposure was performed with focal intensity ISATA = 22.0 x 10(3)
      W/cm2(ISATA, in degassed water) and exposure time 5 sec. The sample was cut after
      treatment to measure the volume of coagulative necrosis. For a specific
      therapeutic transducer, the radiation force ratio in liver of constant thickness
      is independent of the transducer surface sound intensity and the area of the
      ultrasound window at the sample front face. The radiation force ratio and the
      volume of coagulative necrosis induced by HIFU are plotted as the functions of
      sample thickness (or exposed depth), in which it can be seen that these two
      parameters have the same exponential dependence on sample thickness. The
      ultrasound attenuation coefficient alpha in ox liver is shown to be frequency f
      dependent, it almost linearly increases with frequency t. This work shows that
      such a study is feasible, and offers experimental data that will be useful for
      future HIFU dosage studies.

PMID- 14716876
TI  - [Study of multi-factor cognition evoked by binocular disparity].
AB  - It is the aim of studies in cognitive process to understand how the impressive
      cognitive capacity of the human mind is uninterruptedly developed and how the
      process is controlled. We have been focusing attention on the central question
      with stereoscopic research. A multi-channel EEG data acquisition system is
      constructed for cognition studies which not only works perfectly in the EEG
      collection and signal processing of stereoscopic visual evoked potentials(VEP)
      but also is suitable for investigative and clinical use. We have identified the
      fact that the processing of stereoscopic depth information is done in the
      cortical advance functional areas with labeled characteristic signaling of the
      depth related VEP and the results were shown to be of no difference when compared
      with the ones of other investigations. We believe, the stereoscopic depth
      cognition is both a dynamic multi-factor processing process and a consequence of
      depth perception in advanced cortical areas through biological feedback to the
      whole process of visual signal processing. It is our novel and significant
      supposition in the psychophysical study, and the experimental results of the VEP
      are presented in this article.

PMID- 14716877
TI  - [Basic study of biodegradable controlled release chemotherapy].
AB  - This study sought to assess the biocompatibility of P(DA-SA)-Adriamycin, a new
      controlled-release chemotherapy system, in rabbit brain, and to examine its
      controlled release effect both in vitro and in vivo and its curative effects in
      vitro. The reaction of animal brain to the implanted P(DA-SA) or P(DA-SA)
      Adriamycin was observed. The controlled-release profiles in phosphate buffer
      solutions and in rabbit brain were measured by UV spectrometry. Then, through
      flow cytometer, the rate of apoptosis in cultured glioma cells was tested. The
      reaction of rabbit brain to P(DA-SA) polymer was moderate and not significantly
      different from that to Gelfoam. The controlled-release rate of P(DA-SA)
      Adriamycin in vitro and in vivo was stable and the duration of controlled-release
      of P(DA-SA)-Adriamycin spanned three weeks. The rate for apoptosis of glioma
      cells of P(DA-SA)-Adriamycin group was 69.9%, which was significantly higher than
      that of the control group. In conclusion, P (DA-SA)-Adriamycin controlled release
      chemotherapy system that bears curative effect has favorable controlled-release
      effect and good biocompatibility in rabbit brain. This system has potential value
      in treatment of malignant brain tumor.

PMID- 14716878
TI  - [Biological distribution of 131I-HAb18F(ab')2 in patients with hepatocellular
      carcinoma].
AB  - Before 131I-HAb18F(ab')2 administration, 24 cases of mid-term or advanced
      hepatocellular carcinoma(HCC) were given Lugol's Liquid to block the thyroid
      gland, and submitted to hepatic colloid imaging. The cases were randomly divided
      into 3 groups. Then 131I-HAb18F(ab')2 was injected into the target hepatic artery
      with doses of 0.5, 0.75, 1.0 mCi/kg, respectively. At the followed 10, 48, 96 and
      192 hours, 131I-HAb18F(ab')2 distribution in human body was acquired by whole
      body dynamic image with Single photon emission computed tomography(SPECT). The
      results showsed that 131I-HAb18F(ab')2 in tumor tissue was significantly higher
      than that in normal liver tissue and other organs. This difference became obvious
      as time passed. 131I-HAb18F(ab')2 is stable in human body and it can combine with
      HCC tissue specifically. So it is a new medicine deserving further research for
      the treatment of HCC.

PMID- 14716879
TI  - [Pharmacokinetics of scutellarin in rabbits].
AB  - An RP-HPLC was established to determine scutellarin in rabbit plasma and to study
      pharmacokinetics of breviscapine in rabbits. The analytical column was
      DiamonsilTM C18(4.6 mm x 250 mm, 5 microns), the mobile phase consisted of
      methanol, 0.02 mol/L phosphate buffer(adjusted by phosphoric acid to pH 3.0) and
      acetonitrile (65:35:10), the flow rate was 1.0 ml.min-1, the column temperature
      was 25 degrees C and the detection wavelength was 334 nm. The results of the
      pharmacokinetics study showed that the concentration-time curve of scutellarin
      was conformed to two-compartment model, the chief pharmacokinetic parameters were
      as follows: t1/2 alpha 1.29 +/- 0.53 min, t1/2 beta 10.40 +/- 1.97 min, Vc148.1
      +/- 118.6 ml, and CL 57.5 +/- 31.7 ml.min-1.

PMID- 14716880
TI  - [Research on human eye cornea's mathematical model and application in diopter
      correction].
AB  - The excimer laser diopter correction has proven to be efficient and safe. This
      paper presents the principle of excimer laser refractive surgery. Based on
      analyzing the mathematics model of the human eye cornea, the authors have
      proposed a new model which can be used to proceed the myopia, hyperopia,
      astigmatism diopter correction. Also studied were the excimer laser's ablation
      mechanism and the flying-spot scanning technology. The research results have been
      directly applied to Ophthalmic excimer laser system. The correction of diopter is
      well improved.

PMID- 14716881
TI  - [Fuzzy control of the physical training intensity based on neural-network].
AB  - Using computer technique, artificial neural network and fuzzy control theory, we
      have explored a real-time control method for the athlete's physical workload
      intensity in order that the goal of physical training can be reached effectively
      in accordance to the exercise plan. The technique could be useful for improving
      the efficiency of scientific physical training.

PMID- 14716882
TI  - [Preparation of liposome-mediated 99m-technetium-labeled antisense
      oligonucleotides of c-myc mRNA].
AB  - To explore the preparation method of liposome-mediated 99m-technetium-labeled
      antisense oligonucleotides of c-myc mRNA and lay foundations for antisense
      imaging and treatment, antisense oligonucleotides (DNA) with 15 bases and di
      functional chelate, hydrazino nicotinamide derivatives, were synthesized. After
      DNA combined with chelate, they were labeled with 99m-technetium to form
      compounds, 99mTc-chelate-DNA (99mTc-DNA), and were purified through Sep-Pak
      reverse column(C18, Waters) by using methanol and water as eluent. The leaching
      curve was made; the labeling efficiency was calculated. The products were then
      encapsulated with cation liposome to form liposome-mediated 99mTc-DNA. The
      radiochemical purity and stability of the liposome-mediated 99mTc-DNA were tested
      through strip chromatography. The labeling efficiency was 63.37% +/- 3.51% at the
      radioactive concentration of 1480 MBq, 62.52% +/- 3.69% at that of 740 MBq,
      59.82% +/- 5.12% at that of 592 MBq. There were no significant differences
      between these labeling efficiencies. The radiochemical purity was 96.47% +/-
      3.01%. The liposome-mediated radiolabeled antisense oligonucleotides were stable
      after incubation with water or serum. Therefore liposome-mediated radiolabeled
      antisense oligonucleotides could be obtained through hydrazino nicotinamide
      derivatives as di-functional chelate and liposome as vector.

PMID- 14716883
TI  - [Effect of absorbable poly-DL-lactide rods on experimental fracture healing].
AB  - This study was designed to assess the effect of a home-bred poly-DL-lactide
      (PDLLA) rods on experimental fracture healing. An operation was performed to
      create bilateral ulnar and radial fractures of forearm in 15 rabbits. The right
      sides were fixed with 2 PDLLA (Mv = 34 x 10(4), 1.6 mm x 1.6 mm x 30 mm) rods,
      and the contralateral sides were fixed with 2 Kirschner wires to be used as
      controls. After operation, casts were used for external fixation, and the joint
      above and the joint below the fracture were immobilized. The casts were removed
      at the 6th week after operation. The specimens were removed at specific intervals
      between 2 and 12 weeks. Histologically, the light microscopy and scanning
      electron microscopy evaluation of the rabbit ulnar and radial fractures fixation
      revealed that, the fractured bone gradually healed and the PDLLA rods properly
      fixed on the fracture area during the implanted period. However, results suggest
      that internal fixation by absorbable material made the course of fracture healing
      slower than that in the control group, but the osteogenesis appeared to be
      normal. In the absorbable group, the collagenous fiber was characterized by order
      and orientation, and calcified normally. In conclusion, this kind of PDLLA rods
      have an effect on delaying the process of the normal union of fracture and should
      be applicable to fractures where the tissues are rich in blood supply.

PMID- 14716884
TI  - [Apply ICA (independent component analysis) to removing power noise from EEG].
AB  - Power noise is constantly found in EEG signals; thus the acquisition and analysis
      of EEG signals can be strongly influenced. Comparison of the efficiencies of four
      ICA algorithms (Fastica, Extended Infomax, EGLD, Pearson-ICA) and SVD methods in
      extracting power noise in the EEG signals showed that ICA algorithms appear
      insensitive to the noise disturbance, whereas the commonly used SVD method does
      not. By applying the Extended-Infomax ICA with better convergence in this paper,
      it was demonstrated that the power noise contained in the 16-channel EEG signals
      of one Alzheimer-disease patient were removed successfully(the lowest signal
      noise-ratio for power noise is 0 dB). ICA has a possible important value and
      prospect in biomedical signal processing, especially in clinical medical
      engineering.

PMID- 14716885
TI  - [A model study on noninvasive blood glucose measurement with multi-wavelength
      infrared array].
AB  - The concentration of glucose in the blood may soon be measured noninvasively by
      near infrared multi-wavelength sensor array without the painful puncture for
      obtaining a drop of blood. For overcoming the limitation of low measuring
      accurate degree and unstable working state, according to the Lambert-Beer Law,
      the authors analyzed the feature of blood adsorption spectroscopy and designed an
      infrared multi-wavelength blood glucose measuring sensor array to surmount the
      difficulties in noninvasive blood glucose measurement. The key technique, most
      suitable for detecting site and the influencing factors from human body were
      discussed, and the Mixture of Expert(ME) algorithm was adopted in building
      calibration model with multiple parameters of human body. It can overcome the
      existing problems and get more exact blood glucose information from the weak
      changes in spectral signals. Also presented and addressed in this paper are the
      detailed implementing steps of ME and the system, as well as the problems need to
      be solved.

PMID- 14716886
TI  - [Medical image elastic registration smoothed by unconstrained optimized thin
      plate spline].
AB  - Elastic registration of medical image is an important subject in medical image
      processing. Previous work has concentrated on selecting the corresponding
      landmarks manually and then using thin-plate spline interpolating to gain the
      elastic transformation. However, the landmarks extraction is always prone to
      error, which will influence the registration results. Localizing the landmarks
      manually is also difficult and time-consuming. We the optimization theory to
      improve the thin-plate spline interpolation, and based on it, used an automatic
      method to extract the landmarks. Combining these two steps, we have proposed an
      automatic, exact and robust registration method and have gained satisfactory
      registration results.

PMID- 14716887
TI  - [3D display of sequential 2D medical images].
AB  - A detailed review is given in this paper on various current 3D display methods
      for sequential 2D medical images and the new development in 3D medical image
      display. True 3D display, surface rendering, volume rendering, 3D texture mapping
      and distributed collaborative rendering are discussed in depth. For two kinds of
      medical applications: Real-time navigation system and high-fidelity diagnosis in
      computer aided surgery, different 3D display methods are presented.

PMID- 14716888
TI  - [A review of interpolation in multi-dimensional reconstruction of medical
      images].
AB  - Image interpolation techniques were widely applied in medical imaging for image
      generation and post processing. Firstly, traditional interpolation methods were
      listed out in the details of shape-based interpolation and dynamic elastic
      registration interpolation. Secondly, the characteristics, development and
      problems in interpolation of rotary scanning ultrasonic cardiac images were
      analyzed. The relation between interpolation and registration was stated. The
      analysis indicated that excellent methods in rotary scanning interpolation should
      be registration-based methods. At last, several evaluation methods about images
      interpolation were discussed.

PMID- 14716889
TI  - [Research advances in gene-enhanced tissue engineering].
AB  - Gene-enhanced engineering deals with the scientific and technologic endeavour to
      produce cultured cells or polymer matrices transduced with multiple gene vectors
      encoding cytokine cDNA by means of genetic engineering technique, to make
      transduced cells or gene activated matrices highly express according cytokine,
      and then to enhance certain abilities of the artificial tissue. Up to now,
      various genes encoding modulatory species of ribonucleic of proteins such as
      growth factors, receptors, and transcription factors have been used in the
      context of gene-enhanced tissue engineering and expressed within numerous
      tissues, including artificial blood vessels, bone, cartilage, skin and urinary
      system, etc. Many experiments in vitro or in vivo have begun to show good
      prospects and great potential application of the new approach. We believe great
      changes will take place in the research field of tissue engineering due to the
      induction the of genetic engineering, and the new approach will become a very
      promising and valuable tool for therapy.

PMID- 14716890
TI  - [Progress in the study on synergetic control principle of human upper extremity
      and related issues].
AB  - Human upper extremity is the most complex and flexible executor during the human
      movement, coordination analysis of the synergetic control principle of human
      upper extremity is of great significance in trajectory planning and real-time
      control of anthropopathy robots and intelligent prosthesis system. Most studies
      have only been performed within the last 10 years. This paper surveys the
      research in the structure characteristic and redundancy coordination principle of
      human upper extremity, and the developments of various prospects of anthropopathy
      robots, intelligent prosthesis, gymnastic science and rehabilitation evaluation
      are discussed.

PMID- 14716891
TI  - [Review of poly(vinyl alcohol) hydrogel and its compounds in the application of
      artificial cartilage materials].
AB  - Poly(vinyl alcohol) (PVA) hydrogel is a kind of material which has excellent
      biocompatibility and mechanical properties. In this paper, the researches and
      developments of PVA hydrogel preparation and the modifications of PVA with other
      material were introduced. The potential for the use of PVA hydrogels as implant
      materials in cartilage reparation was reviewed.

PMID- 14716892
TI  - [Studies on a kind of new biodegradable material--polycaprolactone and
      developments in medical area].
AB  - Nowadays, there are more and more researches on characters and applications of
      polycaprolactone (PCL). This paper reviews the researches of polycaprolactone,
      including its synthesis, physical and chemical properties, biodegradation,
      absorption properties, and its applications in clinical use and drug delivery
      systems. PCL can be from open ring polymerizaion. It is a kind of semi
      crystalline polymer, and has good flexibility. The degradation reaction of PCL is
      hydrolysis. PCL is not cumulated in the body, and can be totally excreted. It can
      be used as suture, material for fixation of bone fracture, vector of drug, etc.
      PCL is widely used in medical area because of its safety, low toxicity,
      biodegradability.

PMID- 14716893
TI  - [Construction of bioprosthetic heart valve with viable cells].
AB  - The ideal valve substitute should have cellular viability. Cryopreserved
      allograft has cellular viability in some degree, but the quantity, viability and
      function of the cells are affected by some preexistent factors such as chemical
      injury, hypoxia during valve processing and injury at the time of implantation.
      Early cellular autolysis and apoptosis take place not long after implantation,
      the implanted valve thus loses significant capacity to grow, remodel, or exhibit
      active metabolic functions. The viable donor cells are antigenic and capable of
      eliciting immune response, including antigenic and antigen-specific T cells.
      Calcification appears to originate in residual nonviable cells and their
      fragments. Proteinases released from endothelial and fibroblast cells of
      allograft heart valve will lead to the destruction of the valve matrix. One of
      the focuses of creating an ideal heart valve is the progressive recellularization
      of the valve matrix by the autologous cells. The acellular valve matrix, after
      being recellularized, has two characters: cellular viability and normal cellular
      function, which are the bases of creating ideal bioprosthetic valve with the
      potentiality of growing, repairing and remodeling.

PMID- 14716894
TI  - [Transplantation: ethics and stem cells].

PMID- 14716895
TI  - [Brain death criterion--an ethical challenge].

PMID- 14716896
TI  - [Ethics and organ transplantation with living donors].

PMID- 14716897
TI  - [Transplantation immunology].

PMID- 14716898
TI  - [Tissue types].

PMID- 14716899
TI  - [Matching for ABO blood groups and HLA tissue types in transplantation with
      special reference to bone marrow transplantation].

PMID- 14716900
TI  - [Stem cell differentiation--significance of new findings for transplantation
      biology].

PMID- 14716901
TI  - [Allogeneic bone marrow transplantation].

PMID- 14716902
TI  - [Treatment of cancer with high-dose chemotherapy and autologous stem cell
      transplantation].

PMID- 14716903
TI  - [Allogeneic stem cell transplantation in non-malignant diseases].

PMID- 14716904
TI  - [Mesenchymal stem cell therapy--the key to regenerative medicine?].

PMID- 14716905
TI  - [Regeneration of myocardium by stem cell therapy. Historical and biological
      perspective].

PMID- 14716906
TI  - [Islet transplantation in type 1 diabetes. Status and perspectives].

PMID- 14716907
TI  - [Picture of the month: fistula in the penis].

PMID- 14716909
TI  - [Mycobacterium avium subspecies paratuberculosis].

PMID- 14716910
TI  - [Economic drug prescription].

PMID- 14716908
TI  - [The 2003 Nobel Prize in chemistry to Peter Agre for the discovery of aquaporin
      channels].

PMID- 14716911
TI  - [Focus on smoking cessation or drugs?].

PMID- 14716912
TI  - [Occurrence of diabetes in Denmark: development of methods for registry-based
      assessment].

PMID- 14716913
TI  - [Why this restrictive view on surgery for Parkinson disease?].

PMID- 14716914
TI  - [How can the victims of violence, especially those of spouse abuse, be helped?].

PMID- 14716916
TI  - [The new specialist education--a step backwards?].

PMID- 14716917
TI  - Syndemics and public health: reconceptualizing disease in bio-social context.
AB  - The world of public health has undergone dramatic changes since the emergence of
      AIDS in the early 1980s. The appearance and global spread in recent years of wave
      after wave of new and renewed infectious diseases and their entwinement with each
      other and with the social conditions and biopsychological consequences of
      disparity, discrimination, and structural violence has produced a new significant
      threat to public health internationally. The term syndemic has been introduced
      recently by medical anthropologists to label the synergistic interaction of two
      or more coexistent diseases and resultant excess burden of disease. This article
      provides the fullest examination of this new concept to date, including a review
      of relevant new literature and recent research finds concerning coinfection and
      synergistic interaction of diseases and social conditions at the biological and
      population levels.

PMID- 14716918
TI  - Migratory journeys and tuberculosis risk.
AB  - After decades of decline, tuberculosis case rates in New York City more than
      tripled between 1978 and 1992. While the number of cases of those born in the
      United States declined after 1992, the proportion of immigrant tuberculosis cases
      continued to increase and reached 58 percent in 1999. This article questions the
      biomedical explanation of immigrant tuberculosis as being imported from
      immigrants' countries of origin. Illness narratives of illegal Chinese immigrants
      with tuberculosis detailing risks associated with migratory journeys are
      presented. The social and cultural nature of the concept of risk, as well as the
      adverse implication of biomedical identification of immigrants as being at higher
      risk of tuberculosis, are also discussed. The author concludes that the dominant
      biomedical explanation of immigrant tuberculosis could be modified with the
      incorporation of the migratory process as a risk factor.

PMID- 14716919
TI  - Using home gardens to decipher health and healing in the Andes.
AB  - Home gardens are a pervasive component of Andean agricultural systems, but have
      been ignored in anthropological and agronomic research. Recent research in the
      indigenous community of Saraguro, Ecuador, employed a combination of in-depth
      interviews, free-listing, videotaped walk-throughs, and mapping to explore the
      role of home gardens, which are established and controlled by women. Findings
      reveal that, although gardens offer multiple benefits, they are overwhelmingly
      devoted to the cultivation of medicinal plants, operating as de facto medicine
      cabinets that supply women with most of the resources they need to treat family
      illnesses. Results also suggest that the natural history of home gardens mirrors
      transformations within the family, and that Saraguro women study the contents of
      their neighbors' gardens, using this knowledge as a foundation for deciphering
      the owners' economic and health status. New threats to the sustainability of home
      gardens threaten the foundation of Saraguro's ethnomedical system and women's
      authority in the home and community.

PMID- 14716920
TI  - Contextualizing the politics of knowledge: physicians' attitudes toward medicinal
      plants.
AB  - This article examines how a group of public health physicians in the urban Amazon
      values medicinal plant knowledge. As biomedical health care providers, physicians
      routinely draw on scientific plant knowledge. At the same time, as residents of
      the Amazon and health care providers to the poor, they are aware of and sometimes
      participate in local systems of plant knowledge. When discussing medicinal plant
      use, physicians repeatedly mention three themes: science, superstition, and
      biopiracy. The way in which physicians construct and negotiate these themes is
      part of the process of maintaining and legitimating their expertise and
      authority. This analysis finds that context is key to understanding whether,
      when, and why physicians value certain bodies of knowledge. Locally, in clinics,
      scientific plant knowledge is constructed as superior. In a global context,
      however, local plant knowledge is explicitly valued. This situational
      valuation/devaluation of plant knowledge relates to the positions of power
      physicians occupy in each context.

PMID- 14716921
TI  - A time for ethical leadership. ACHE affiliates can provide the moral leadership
      our nation's healthcare system needs.

PMID- 14716922
TI  - Strengthening the safety net.
AB  - If you've ever built a house of cards or played a game of Jenga, you know how
      quickly an ill-timed move can destroy your goal of maintaining equilibrium. The
      consequence of upsetting one piece of the whole is a common metaphor many safety
      net providers use to help other healthcare organizations understand their role in
      the system. The fiscal and physical pressure on just one safety net provider can
      create a dangerous ripple effect in a community, threatening the stability of
      other area providers and access to care for the patients they serve. "We have
      created a complicated tension within our healthcare system," says Stuart H.
      Altman, Ph.D., HFACHE, professor, National Health Policy, at Brandeis University
      in Waltham, MA. "If any single major sector of the system is out of balance, the
      others will be affected in a very negative way." Depending (in part) on geography
      as well as local and state politics, the fate of "non"-safety net providers can
      hinge on the success of those organizations whose primary mission is to provide
      indigent care. "If the safety net fails, the whole healthcare system could
      potentially collapse because the remaining providers simply cannot handle all of
      the demand," says C. Duane Dauner, FACHE, president of the California Healthcare
      Association in Sacramento. The current situations in Washington, D.C., Dallas,
      and several California counties illustrate this domino effect Dauner describes.

PMID- 14716923
TI  - Innovative programs provide access to care.

PMID- 14716924
TI  - A race/ethnic comparison of career attainments in healthcare management--2002.
      Recommendations.
AB  - In 2002, the American College of Healthcare Executives--in collaboration with the
      Association of Hispanic Healthcare Executives, the Executive Leadership
      Development Program of the Indian Health Service, the Institute for Diversity in
      Health Management, and the National Association of Health Services Executives-
      conducted a comprehensive survey that compared the career attainments of
      healthcare executives by race/ethnicity. The findings, which were published in
      the November/December 2003 issue of Healthcare Executive and are available online
      at www.ache.org/pubs/research/research.cfm, showed that minorities continue to
      lag behind Whites in several areas, including total median compensation, senior
      level job obtainment, and job satisfaction. In response to these continuing
      inequities, the Board of Governors of the American College of Healthcare
      Executives recommends the following initiatives.

PMID- 14716925
TI  - Leadership. Fostering trust in the workplace.

PMID- 14716926
TI  - Executive Q&A. Management staff development.

PMID- 14716927
TI  - Compliance and ethics: a critical interdependence. Behaving ethically means more
      than just doing things right--it means doing the right things.

PMID- 14716928
TI  - Knowing your customer. Identify who your customers are so you can respond to what
      they need.

PMID- 14716929
TI  - Confronting specialty competition. Hospitals should consider both strategic and
      facility design approaches.

PMID- 14716930
TI  - Improving emergency department flow. Eliminating ED inefficiencies reduces
      patient wait times.

PMID- 14716931
TI  - Life cycle of physician executives. Life-cycle phases for physician executives
      provide order in a turbulent environment.

PMID- 14716932
TI  - When the search consultant calls. A nationally recognized authority shares tips
      for working with search consultants.

PMID- 14716933
TI  - Preparing for the Medicare drug benefit. The proposed Medicare legislation spells
      tough times ahead for most providers.

PMID- 14716934
TI  - Decreasing high-risk behavior in teens. A theater program empowers students to
      reach out to their peers.

PMID- 14716935
TI  - Invest in tomorrow's leaders. Affiliated group members can interact with students
      in a variety of ways.

PMID- 14716936
TI  - Challenges in geriatric medicine: geriatric services and education.

PMID- 14716937
TI  - Aged care services in Singapore--an overview.
AB  - INTRODUCTION: Aged care services have been rapidly and systematically established
      in Singapore over the past two decades in anticipation of the challenges that
      will accompany the rapid ageing of our population. This paper presents an
      overview of the geriatric services that have developed in Singapore, funding for
      these services, and aged care-related training programmes for doctors and nurses
      in Singapore. METHODS: A non-systematic review of journal articles, local
      conference proceedings and state publications was undertaken. RESULTS: Geriatric
      services have evolved rapidly with the establishment of 3 acute geriatric
      medicine units covering the different sectors of Singapore. Apart from the
      provision of acute medical care for older persons, geriatricians have also been
      increasingly involved in the enhancement of community aged care services under
      the Framework for Integrated Health Services for the Elderly. Concurrently,
      community services for the elderly have blossomed under the leadership provided
      by various voluntary welfare organisation. Innovative systems of funding the
      healthcare needs of older persons have also evolved over the past few years. In
      recognition of the increasing needs of our ageing population, the medical
      training curriculum is being continually reviewed to enhance the skills of
      medical practitioners in Singapore. CONCLUSION: Over a short span of 20 years, a
      comprehensive framework of services has been developed to meet the needs of our
      ageing population. While much has been accomplished, there is a need for
      continuous review of our services and healthcare policies to identify areas for
      further improvement.

PMID- 14716938
TI  - Aged care issues and services in Australia.
AB  - INTRODUCTION: This paper examines aged care issues and the provision of aged care
      services in Australia. MATERIALS AND METHODS: A Medline search and review of
      Australian government publications was undertaken and complemented by a review of
      local Australian resources. RESULTS: Australia has seen major development of aged
      care services over the last 60 years. These services were originally focused on a
      residential care model, but have since evolved to become a mixed provision of
      services that are shaped by legislative or regulatory requirements. Geriatric
      health services are well-developed in some parts of Australia, with a
      comprehensive regional service that includes hospital-based and community-based
      components (including an Aged Care Assessment Team). CONCLUSION: The rapidly
      ageing population in Australia is exerting pressure on the aged care system and
      geriatric health services. A major identified problem with available services is
      their fragmentation and limited co-ordination.

PMID- 14716939
TI  - The development of geriatric psychiatry services in Singapore.
AB  - Singapore is ageing rapidly and the need to develop a comprehensive range of
      psychiatric services for the elderly is urgent. To cater to the increase in the
      number of elderly with mental health problems, a multi-pronged, collaborative
      approach to developing services is necessary. Over the last decade, the
      development of such services has been initiated by the Department of Geriatric
      Psychiatry, Woodbridge Hospital and Institute of Mental Health, and effected
      through dynamic elderly networks consisting of health, social and voluntary
      organisations. This has facilitated the integration of psychogeriatric services
      within the overall framework of elderly services. With the establishment of the
      Integrated Framework of Healthcare of the Elderly by the Ministry of Health in
      2000, the importance and effectiveness of building partnerships in service
      provision have been demonstrated. The challenge for the future is to attract and
      retain geriatric-trained healthcare professionals, enhance their training in the
      early diagnosis and management of psychiatric disorders in the elderly, improve
      the support of family caregivers and expand the range of quality psychogeriatric
      services.

PMID- 14716940
TI  - Urinary incontinence in older persons: a simple approach to a complex problem.
AB  - Urinary incontinence is a major geriatric syndrome with significant morbidity and
      even mortality. However, it is under-recognised and inadequately managed despite
      its impact and cost. Continence in the older person is maintained by the fine
      balance between the integrity of the lower urinary tract, the cognitive ability
      and motivation to keep dry, and adequate mobility and dexterity to void;
      impairment of any of the three can result in incontinence. The management of
      older persons with urinary incontinence involves, i) identifying and reversing
      transient incontinence, ii) excluding urinary retention, iii) deciding on the
      need of special tests (imaging, screening for malignancy, magnetic resonance
      imaging [MRI] for spinal cord, urodynamic assessment) to exclude sinister causes,
      and iv) deciding on the need to refer the specialist. With careful evaluation,
      continence in the older persons can be restored in most cases.

PMID- 14716941
TI  - An evidence-based clinical approach to the diagnosis of dementia.
AB  - With the rapidly ageing population in Singapore, dementia prevalence is on the
      rise. Early diagnosis is important as dementia impacts not only on patients and
      their families, but also on the community and healthcare system as a whole; with
      early treatment plans drawn up, the suffering associated with this illness can be
      more effectively and efficiently managed. In this paper, we present a 4-step,
      evidence-based assessment strategy for primary care physicians, which cover the
      essential objectives of the dementia evaluation, incorporating local data where
      possible. The first step requires the important exclusion of delirium as the
      cause of forgetfulness or confusion. The second step involves clinically
      establishing that the patient's chronic confusional state is due to dementia. The
      third step looks at the behavioural, functional and social dimensions of
      dementia. The final step determines the aetiology of dementia with the use of a
      focused history, physical examination, a predefined battery of haematological
      tests and, in selected cases, structural neuroimaging.

PMID- 14716942
TI  - Assessing decision-making capacity in dementia patients: a semi-structured
      approach.
AB  - One of the consequences of the rapidly increasing numbers of dementia patients in
      Singapore will be the need for all clinicians (including non-psychiatrists) to be
      familiar with the fundamentals of how decision-making capacity should be
      assessed. The clinical settings when the need for such evaluations arise, often
      involve cognitively or emotionally impaired patients who are required to make
      treatment, placement, financial or testamentary decisions. The clinician must
      first diagnose the patient's psychopathology and then go onto testing the
      functional abilities involved in decision-making. These comprise (1) making and
      expressing a choice, (2) understanding the relevant information, (3) appreciating
      the relevance of the information to oneself and (4) reasoning with the given
      information. The eventual judgement of the patient's decision-making capacity
      involves the weighing of impairment noted in any of the four decisional abilities
      against the potential adverse consequences of abiding by the patient's decision.
      The ethical impulse underlying this manner of judgement balances the respecting
      of patient's autonomy with protecting the patient from harm. Given the relative
      complexity of the assessment process, there is merit in developing a semi
      structured approach to the evaluation of patients' decision-making capabilities;
      such an approach can guide a wider group of clinicians and psychologists through
      the essential steps of the process and thus enable the assessment to be more
      thorough, as well as fairer, to the patient.

PMID- 14716943
TI  - Neurofibrillary and ethico-legal tangles: in search of surrogates for dementia
      patients lacking decision-making capacity and relatives.
AB  - Singapore's greying population has led to an alarming increase in the prevalence
      of dementia, and inevitably to a rising number of dementia patients who lack
      competence and relatives. Although legislative provisions exist in the current
      Mental Disorders and Treatment Act (MDTA) for the appointment of committees of
      person and estate for incompetent patients, healthcare professionals continue to
      face challenging obstacles in their attempts to search for appropriate surrogate
      decision-makers for such patients. We illustrate, with 2 cases from our clinical
      experience, the ethical, legal and administrative tangles faced in our search for
      appropriate surrogate decision-makers. Specific problems, such as administrative
      ambiguities in applying the MDTA and the impracticalities of a rigorous judicial
      process in appointing surrogates, are discussed. We propose possible solutions
      how these obstacles can be effectively tackled, in particular adopting a radical
      shift from the present judiciary model to a clinical-based model of appointing
      surrogates for healthcare decisions. This clinical model is based on best
      interests considerations and emphasies peer review and a multidisciplinary
      consultative approach in determining the clinical merits of proposed treatment
      and its impact on quality of life. The ultimate aim of such a change is to
      facilitate timely medical care while ensuring ethical practices that respect the
      patient's dignity.

PMID- 14716944
TI  - Late-life depression: current issues and new challenges.
AB  - INTRODUCTION: Depression is a common psychiatric disorder in older people but
      tends to be underrecognised and undertreated, leading to impaired functioning,
      increased morbidity and mortality including suicide, and greater service
      utilisation. METHODS: A Medline search of journal articles on depression in older
      people, which highlighted specific and pertinent issues of prevalence,
      classification, screening instruments, elderly suicide and various treatment
      modalities, was done. RESULTS: Late-life depression represents a heterogenous
      group of mood disturbances that may present with atypical features and occur in a
      complex medical psychosocial context. Appropriate screening and assessment
      procedures and holistic, multidisciplinary treatment approaches are discussed.
      Future challenges lie in areas of early detection and intervention, advances in
      treatment strategies, training and service developments and effective prevention
      programmes. CONCLUSION: By raising awareness and understanding of depression
      among primary healthcare and other healthcare practitioners, more depressed
      elderly with comorbid medical problems can be successfully identified and helped.

PMID- 14716945
TI  - Considerations in the assessment and management of older people with chronic
      pain.
AB  - INTRODUCTION: The aim of the paper is to describe the philosophical underpinnings
      and methodologies in the management of chronic pain in older people. METHODS: The
      paper represents a summary of the data concerning the management of pain in older
      people. These data have been gleaned from various sources, including textbooks,
      reviews, original papers and conference reports. RESULTS: Persistent pain affects
      approximately 50% of the older population above 65 years. Chronic pain describes
      a syndrome of persistent pain and accompanying adverse psychosocial consequences
      and functional disabilities. This is believed to be an inaccurate appraisal of
      the nociceptive stimulus by the patient. Assessment is based on a
      multidisciplinary cognitive-behavioural model. Management consisting of a
      seamless blend of pharmacological, physical and psychological therapies is likely
      to yield the best results. CONCLUSION: Chronic pain in older people is an
      emerging problem in the specialty of geriatric medicine. The traditional
      multidisciplinary approach is likely to give good results.

PMID- 14716946
TI  - A palliative care approach to end-stage neurodegenerative conditions.
AB  - INTRODUCTION: Neurodegenerative conditions, such as Alzheimer's disease,
      Parkinson's disease and motor neurone disease, are progressive and incurable
      conditions that ultimately lead to a state of total functional incapacitation and
      death. These conditions are "terminal" and, therefore, should be managed with a
      palliative care approach. This article highlights some of the issues in caring
      for patients with end-stage neurodegenerative conditions from a palliative
      perspective. METHODS: This review is based on evidence from pre-existing medical
      literature on the above subject and the authors' personal experiences and
      observations. CONCLUSION: Patients with end-stage neurodegenerative conditions
      have needs similar to that of advanced cancer patients. Therefore, the principles
      and practice of palliative care should be applied to such patients. This may also
      mean that palliative care training should be undertaken in nursing homes, where a
      large number of such patients are located.

PMID- 14716947
TI  - End-of-life care: challenges and obligations in setting limits to life-sustaining
      therapy.
AB  - It is now generally accepted that the withholding or withdrawal of interventions
      that serve only to prolong the dying process is appropriate. Setting limits to
      life-sustaining therapy are now common practice. However, making such decisions
      can be challenging. They are also not uncommonly a source of disagreement between
      the physician and the patient or surrogate. The potential for strained patient
      physician relationship can be mitigated by patient-centred, goal-specific care
      with its emphasis on effective communication, a sense of timing and attention to
      the various dimensions of the illness experience.

PMID- 14716948
TI  - Bedside clinical methods useful as screening test for aspiration in elderly
      patients with recent and previous strokes.
AB  - INTRODUCTION: This study was undertaken to ascertain the usefulness of clinical
      screening tools for dysphagia in a heterogeneous group of older stroke patients.
      The usefulness of bedside clinical assessment tools for detecting dysphagia on
      different consistencies of feeds was also studied. MATERIALS AND METHODS: Fifty
      patients referred to a speech therapist for the assessment of possible dysphagia
      were recruited. The clinical tools studied included the water swallow test, the
      oxygen desaturation test and the combination of both tests (termed "clinical
      aspiration test"). The outcomes of the clinical assessments were compared with a
      fibreoptic endoscopic examination of swallowing (FEES) conducted at the same
      sitting. Fifty patients underwent an examination of their ability to swallow 50
      mL of water in 10-mL aliquots. They underwent a FEES with different food
      consistencies by a speech therapist and oxygen saturation with pulse oximetry was
      monitored during the procedure. Oxygen desaturation of more than 2% was
      considered to be clinically significant. RESULTS: The water swallow test had a
      sensitivity of 79.4% and specificity of 62.5% for the detection of aspiration,
      with a positive predictive value (PPV) of 81.8% and a negative predictive value
      (NPV) of 58.8%. The oxygen desaturation test had a sensitivity of 55.9% and a
      specificity of 100% with PPV of 100% and NPV of 51.6%. When both tests were
      combined, a sensitivity of 94.1% and a specificity of 62.5% was attained, with
      PPV of 84.2% and NPV of 83.3%. Using the clinical assessment test, we were able
      to pick up 3 aspirators who would otherwise have been missed if they were
      assessed with the water swallow test using thin fluids alone. CONCLUSION: Simple
      clinical assessment tools can be used to screen for dysphagia in a heterogeneous
      group of older patients with stroke disease, and clinical testing using feeds of
      different consistencies should be considered.

PMID- 14716949
TI  - Nursing home falls: a local perspective.
AB  - INTRODUCTION: This study aims to examine the demography of falls, factors that
      contribute to falls and fall risk factors in residents of a nursing home for the
      elderly in Singapore. MATERIALS AND METHODS: An 18-month follow-up study was
      carried out on 95 nursing home residents. Information on the subjects' potential
      risk factors for falls was obtained through a review of their casenotes and
      physical examination. At the end of the study period, the casenotes were reviewed
      for any documented fall, the circumstances surrounding each fall and whether
      complications resulted from the fall. The likely factors and events associated
      with each fall were categorised where possible. Logistic regression was performed
      to determine the risk factors for falls. Subjects who died or were discharged
      during the study were included in the analysis. RESULTS: Several subjects (72.6%)
      were > or = 75 years old, required assistance in activities of daily living
      (71.6%), cognitively impaired (52.6%), diagnosed with mental illness (49.5%) and
      non-ambulant (43.2%). A total of 63 falls contributed by 38 (40%) subjects were
      documented over 18 months, giving an incidence of 0.5 fall per bed year. Thirteen
      (20.6%) injuries resulted from the falls, of which 3 were fractures. Falls
      associated with both intrinsic and extrinsic factors were identified in 38.1% of
      falls. The most common intrinsic factors were gait disorders (31.7%) and
      confusion/difficult behaviour (31.7%). Contributory extrinsic factors include
      wheelchair/commode (22.2%) and bathroom-related (15.9%) incidents. Most falls
      occurred during ambulation (31.7%) and transfers (17.5%). On multivariate
      logistic regression, the only significant risk factors for falls were "need for
      ambulatory aids" (odds ratio, 24.4) and "cognitive impairment" (odds ratio, 8.1).
      CONCLUSION: The study confirms that falls are common amongst elderly in a local
      nursing home. Residents with gait instability and behavioural problems due to
      underlying dementia or mental illnesses are most at risk. Extrinsic factors, such
      as bathroom activities and the use of wheelchair/commodes, are contributory.
      Thus, falls reduction protocols in nursing homes should include behavioural
      measures, enhanced care practices and environmental modifications to be
      effective.

PMID- 14716950
TI  - Correlates of habitual walking and sports/leisure-time physical activity in older
      persons in Singapore: interaction effects between educational attainment and
      gender.
AB  - INTRODUCTION: We examined for demographic and psychosocial correlates on the
      participation of habitual walking and sports/leisure-time physical activity
      (LTPA) among older persons in Singapore. MATERIALS AND METHODS: In an
      observational study, 177 Chinese, community/urban-dwelling, ambulant, non
      disabled participants > or = 50 years old were recruited from a health promotion
      programme. The main outcome measures were self-reported participation in habitual
      walking and sports/LTPA. Variables examined include highest educational
      attainment, demographic and health characteristics, social contact and health
      knowledge. Interaction between gender and educational attainment was also
      examined. RESULTS: The mean age of participants was 62.5 +/- 7.8 years. The
      effects of educational level were significant on habitual walking (P = 0.02),
      while that of age, self-rated health and interaction between gender and
      educational level were significant for sports/LTPA (P = 0.012, P = 0.002 and P =
      0.019, respectively). Men with higher education had a higher self-reported
      sport/LTPA, while in women; those with lower education attainment had a higher
      participation. CONCLUSION: Unlike findings from Western developed nations,
      previous studies done in Japan and Singapore found that educational level and
      health behaviours may not be positively associated. In this study, there is a
      negative correlation between educational attainment and participation in habitual
      walking and sports/LTPA, especially among older Singaporean women.

PMID- 14716951
TI  - The Internet as a source of health information among Singaporeans: prevalence,
      patterns of health surfing and impact on health behaviour.
AB  - OBJECTIVE: The Internet is an increasingly popular source of healthcare
      information. This study describes the prevalence of health surfers in Singapore
      and their health-surfing patterns. It also assesses their confidence in online
      health information and the impact the Internet has on health-seeking behaviour.
      MATERIALS AND METHODS: A cross-sectional survey using a standardised
      questionnaire was carried out among residents aged 13 to 55 years in 1852 units
      in Bishan North. These units were selected by single-stage simple random cluster
      sampling method. RESULTS: The household response rate was 51% (n = 950) and the
      individual response rate was 69% (n = 1646). Responding and non-responding
      households were similar in terms of ethnicity and housing type. Of the
      responders, 62.9% surfed the Internet and 37.7% have surfed for health
      information. Health surfers tended to be younger (20 to 39 years) and have higher
      education status. Indians were also more likely than other ethnic groups to surf
      for health. Professional health-related sites comprised the majority (68%) of
      sites visited, and the most common search keywords concern chronic degenerative
      diseases, e.g. hypertension. The top preferred sources of health information were
      doctors (25.9%), the Internet (25.3%) and the traditional mass media (20.5%).
      Almost half (45.1%) considered online health information trustworthy if it was
      from a professional source or if the website displayed the source, while 10.6%
      trusted the information if it concurred with the doctors' advice. The vast
      majority (91.7%) had taken some action in response to the information.
      CONCLUSION: The Internet is being used as an accessible source of health
      information by a substantial proportion of the lay public. While this can
      facilitate greater partnership in healthcare, it underlines the need for doctors
      to be pro-active in the practice of evidence-based medicine, and for guidelines
      to enable patients to use this tool in a discerning manner.

PMID- 14716952
TI  - A prospective audit of critical incidents in anaesthesia in a university teaching
      hospital.
AB  - INTRODUCTION: We aimed to reduce mortality and morbidity in anaesthesia by
      identifying common factors contributing to critical incidences and 'near misses'.
      MATERIALS AND METHODS: We carried out a prospective survey over a 2-year period
      from May 1999 to April 2001 of all reported critical incidents in patients
      undergoing anaesthesia. Critical incidents were reported anonymously, using the
      Anaesthetic Incident Monitoring Study form. This consisted of structured
      questions with tick box answers. Completed forms were reviewed and after open
      discussion with the department, preventive strategies and guidelines were
      developed and introduced. RESULTS: A total of 116 critical incidences were
      reported in 108 patients. These are events that have resulted or could have
      resulted in an adverse outcome for the patient. Airway incidences were the
      commonest incidence reported (33.6%), followed by pharmacological problems like
      wrong drug or dose (28.4%). These occurred most often during maintenance and
      recovery from anaesthesia largely due to human factors like inattention, haste
      and failure to check equipment. They were preventable in 76% of cases. As a
      consequence, 33.6% of incidents resulted in cardiac arrest or major physiological
      change. There was no adverse outcome in 36.2%. From a review of the critical
      incident reporting, organisation of manpower was improved to ensure adequate
      supervision of junior staff. Checking of equipment and drug before use was
      constantly emphasized. CONCLUSION: Critical incident reporting is a useful tool
      for quality assurance programmes. It analyses human and systems problems to
      ensure improved patient care.

PMID- 14716953
TI  - Burch colposuspension: review of perioperative complications at a women's and
      children's hospital in Singapore.
AB  - INTRODUCTION: This study aims to determine perioperative complications of Burch
      colposuspension. MATERIALS AND METHODS: A retrospective casenote review was
      conducted on all cases of Burch colposuspension performed or supervised by a
      single, trained urogynaecologist between January 1998 and December 2001. RESULTS:
      Of the 250 women, 151 (60.4%) had Burch colposuspension in conjunction with other
      procedures. The other procedures included 117 hysterectomies, 15 sacrocolpopexies
      and hysterectomies, 11 sacrocolpopexies, 4 sacrohysteropexies, 3 posterior
      repairs and 1 ovarian cystectomy. Data from the 99 women who underwent only Burch
      colposuspension were analysed. Eight (8.1%) women had blood loss of > 500 mL; of
      these 3 lost > 1000 mL. Three (3%) women required blood transfusion. Urinary
      retention occurred in 13 (13.1%) women for > 10 days and 4 (4%) women required
      catheterisation for between 21 and 29 days. Wound infection/haematoma, gross
      haematuria and febrile illness accounted for 2 (2%), 20 (20.2%) and 6 (6%) cases,
      respectively. One (1%) woman, who had 3 previous pelvic surgeries, required
      reoperation for repair of ureteric injury. CONCLUSION: Burch colposuspension
      should be performed or supervised by trained instructors who must anticipate
      potential problems, especially in women with previous pelvic surgeries, before
      they get worse. There should be strict criteria of the number of Burch
      colposuspension observed and assisted, before performing them supervised.

PMID- 14716954
TI  - Outcomes of acute arthroscopic repair and conservative treatment following first
      traumatic dislocation of the shoulder joint in young patients.
AB  - INTRODUCTION: The aim of this study was to compare patients who had arthroscopic
      repair done following the first traumatic dislocation with patients who were
      treated conservatively, in terms of stability and function. MATERIALS AND
      METHODS: Acute arthroscopic Bankart repair with absorbable tack was used in 30
      shoulders after the first dislocation, while 32 patients who sustained traumatic
      anterior dislocation were treated conservatively at Gulhane Military Medical
      Academy, Department of Orthopaedics and Traumatology between March 1997 and April
      2001. Preoperative and postoperative range of motion of the shoulder and Constant
      score of all patients were recorded. RESULTS: In the conservative group, the
      average pretreatment Constant score was 46.8 (range, 30 to 70) and the average
      post-treatment Constant score was 71.4 (range, 30 to 95). In the surgical group,
      the average preoperative Constant score in cases with Bankart lesion was 44.7
      (range, 30 to 60) and the average postoperative Constant score was 92.3 (range,
      65 to 100), (P = 0.0001). CONCLUSION: Our results support the use of acute
      arthroscopic repair of traumatic anterior shoulder dislocations with absorbable
      tacks. Arthroscopic repair is the treatment of choice in young and active
      patients who are having their first traumatic dislocation.

PMID- 14716955
TI  - Remifentanil in the management of laparoscopic resection of phaeochromocytoma-
      case reports.
AB  - INTRODUCTION: The laparoscopic adrenalectomy approach to phaeochromocytoma
      surgery offers the opportunity to use new short-acting drugs to facilitate rapid
      recovery. CLINICAL PICTURE: We report on 2 cases who underwent laparoscopic
      resection of phaeochromocytoma. The first was a 40-year-old lady who had been
      started on phenoxybenzamine 20 mg bd, but developed a recurrence of bronchial
      asthma after starting atenolol which was subsequently stopped. The second was a
      51-year-old lady with neurofibromatosis who was taking phenoxybenzamine 20 mg bd
      and propanolol 20 mg tds. TREATMENT: The intraoperative management was
      facilitated by the stress suppressive effects of remifentanil infusion combined
      with nitroprusside as a vasodilator, and desflurane as an anaesthetic. OUTCOME:
      Both patients were extubated at the end of surgery and made uneventful recovery.
      CONCLUSION: Remifentanil possesses several useful properties, which deserve
      serious consideration in phaeochromocytoma surgery, particularly in the instance
      where beta-blockade is contraindicated. In combination with other titratable
      short-acting agents, it potentially facilitates rapid recovery especially
      following the laparoscopic approach to adrenalectomy.

PMID- 14716956
TI  - Giant pericardial lipoma: unusual cause of intrathoracic mass.
AB  - INTRODUCTION: Pericardial lipomas are rare clinical findings. We describe a case
      of pericardial/epicardial lipoma seen recently at our hospital. CLINICAL PICTURE:
      A 68-year-old lady presented with a 1-year history of dull aching upper abdominal
      pain. A chest X-ray revealed a large mass lesion in the right hemithorax.
      Computed tomography (CT) scan of the chest defined the nature of the lesion. CT
      guided fine needle aspiration cytology showed mature fat cells. TREATMENT: The
      large lipoma (19 x 10 x 4 cm, 1500 g) was completely excised along with a block
      of the parietal pericardium; through standard right posterolateral thoracotomy.
      OUTCOME: The patient had an uneventful postoperative recovery. She is currently
      asymptomatic and has no evidence of recurrence at 18 months follow-up.
      CONCLUSION: Lipomas in the thoracic cavity are rare and pericardial lipomas even
      rarer. These are best identified on imaging studies including a CT scan. Complete
      surgical excision of the lipoma is the only mode of treatment and adequate
      surgery the only way to prevent future recurrences.

PMID- 14716957
TI  - Clinical profile and treatment outcome of livedoid vasculitis: a case series.
AB  - INTRODUCTION: Livedoid vasculitis is a painful ulcerative condition affecting the
      legs that is often difficult to treat. In this case series, the clinical profile
      of 6 patients with livedoid vasculitis and their treatment response to aspirin
      and pentoxifylline are reported. MATERIALS AND METHODS: This is an open trial.
      Investigations to exclude secondary causes of livedoid vasculitis were done. Skin
      biopsies were performed for histology and direct immunofluorescence. Four
      patients were treated with pentoxifylline and 2 with aspirin. Response to
      treatment was assessed at the third and sixth weeks. Thereafter, treatment was
      individualised according to each patient's clinical response. RESULTS: Only 1 out
      of 6 patients had a good response. This patient was treated with pentoxifylline.
      Most patients required treatment with drugs such as prednisolone, colchicine and
      azathioprine to control disease activity after the trial period. CONCLUSION:
      Pentoxifylline or aspirin did not result in significant improvement for most of
      our patients when used alone. Combination with immunosuppressive treatment
      yielded better results.

PMID- 14716958
TI  - Acute embolic occlusion of the superior mesenteric artery: a case report and
      discussion of management.
AB  - INTRODUCTION: We present a case of acute embolus to the superior mesenteric
      artery (SMA). CLINICAL PICTURE: A 70-year-old gentleman with atrial fibrillation
      complained of colicky abdominal pain with clinical signs of tenderness and mild
      guarding. TREATMENT AND OUTCOME: Laparotomy revealed extensive bowel ischaemia
      but no overt infarction. The SMA was occluded by an embolus at the root of the
      mesentery and balloon catheter embolectomy was carried out at once. Bowel
      resection was deferred in order to allow clear demarcation of gangrene to avoid
      sacrificing unnecessary length. At second look laparotomy, 1.2 m of bowel from
      mid-jejunum to mid-ileum was resected, salvaging about 1 m of previously dusky
      small and large bowel. CONCLUSION: This case illustrates the importance of
      accurate history taking, the role of early intervention and the usefulness of a
      second look laparotomy in cases of mesenteric ischaemia to minimise the extent of
      bowel resection.

PMID- 14716959
TI  - The early years of otolaryngology in Singapore--1946 to 1977.

PMID- 14716960
TI  - Is healthcare competition healthy?

PMID- 14716961
TI  - [Clinical and biological surveillance after the cessation of Hymenoptera venom
      desensitization].
AB  - 107 patients have discontinued Hymenoptera venom immunotherapy between 1988 and
      2000. 31 have been seen again with intradermal tests with IgEs, and 81 responded
      to a questionnaire. Intradermal reactions and IgEs decrease together
      significantly during immunotherapy and then persist at low level during three
      years. Beyond, the number of patients is insufficient. 32 patients were stung by
      the same Hymenoptera and not had any systemic reaction. However, five have beta
      blockers, three have IEC and half of the patients don't take precautions to avoid
      Hymenoptera.

PMID- 14716962
TI  - [Respiratory allergy and domestic animals].
AB  - Pets must be considered allergy factors. They are not advised for atopic
      families. However some recent publications suggest a protective effect of cat and
      dog exposure in the first year of life. The origin of this protective effect is
      not known.

PMID- 14716963
TI  - [Allergies in orthodontics].
AB  - In contrast with work-related allergies amongst dentists and dental
      prosthetictists, allergies in patients followed in orthodontics concerning the
      materials placed in the mouth were rare. It may be a question of limited
      manifestations in the buccal cavity (urticaria, angio-oedema, stomatitis,
      chellitis), or more generalised manifestations (Quincke's oedema, eczema). The
      number of materials used in orthodontics is limited. The observations concerning
      metals are less numerous whilst those that concern the resins are exceptional. On
      the other hand, the risk linked to latex is very real. Allergy investigations
      require skin tests, sometimes to mucous tests and in some cases to provocation
      tests. Use of eviction measures may be not only the only diagnostic method but
      also a therapeutic method. Systematic search for an allergy to metal or a resin
      posed by the prosthetic material does not seem to be necessary. In the case of
      suspicion of latex, confirmed ultimately by an allergic history, this imposes
      start of the eviction measures.

PMID- 14716964
TI  - [Rhinoconjunctivitis: importance of a local diagnosis?].
AB  - Diagnosis of allergic rhinoconjunctivitis, particularly in chronic forms, remains
      sometimes difficult. Systemic tests such as skin or blood tests may be not
      sufficient to assess local sensitization. Local tests are needed, performed from
      nasal secretion or tears. Measurement of total IgE in the local secretions of 41
      patients suffering from rhinoconjunctivitis show that diagnosis contribution was
      upgraded from 61 to 88%. Very interestingly, in some cases, local tests were the
      only argument for allergy.

PMID- 14716965
TI  - [A fixed combination of fluticasone and salmeterol permits better control of
      asthma than a beclomethasone dipropionate and montelukast combination].
AB  - It is now recommended to add an inhaled long-acting beta 2-agonist, or as an
      alternative, to add a leukotriene-antagonist, in patients whose asthma is
      insufficiently controlled with an inhaled corticosteroid alone. A randomised,
      multicentre, open-label, parallel-group study was carried out in 246 patients of
      at least 15 years, whose asthma was not adequately controlled with a medium dose
      of an inhaled corticosteroid. They received either fluticasone/salmeterol
      combination 250/50 micrograms one inhalation twice daily or CFC beclomethasone
      dipropionate 250 micrograms two puffs twice daily plus montelukast 10 mg in the
      evening for 12 weeks. The mean morning PEFR (main criterion) was significantly (p
      = 0.017) more improved with fluticasone/salmeterol (+44.2 L/min) than with
      beclomethasone dipropionate plus montelukast (+31.0 L/min). Other outcomes showed
      significantly better improvements (p 0.022 Pound) with fluticasone/salmeterol
      than with beclomethasone plus montelukast. The two treatments were well
      tolerated. Fluticasone/salmeterol provided a better asthma control than
      beclomethasone dipropionate plus montelukast in patients insufficiently
      controlled with an inhaled corticosteroid alone.

PMID- 14716966
TI  - [Emergency situations in the North Caucasus and role of specific
      immunoprophylaxis in eradication and prevention of epidemiological consequences].
AB  - Information on emergency situations (ES) on the territory of the North Caucasus
      from the 90s of the last century till the present moment is presented. The
      importance of the specific immunoprophylaxis of infections for the liquidation of
      epidemiological aggravations in ES and for their prevention is shown. Information
      on the scope of specific immunoprophylaxis in the zones of ES and on different
      approaches to its carrying out. The conclusion was made on the expediency of
      making corrections in the normative documents of the Ministry of Health of the
      Russian Federation, regulating planned vaccinations and vaccinations made on
      epidemic indications in connection with different kinds of ES.

PMID- 14716967
TI  - [Basic measures for prevention of the epidemiological consequences of a natural
      disaster in the North Caucasus in 2002].
AB  - The system of organizational and prophylactic measures, carried out with a view
      to prevent epidemiological aggravations in connection with the natural calamity
      in the Southern Federal District of the Russian Federation in 2003, is described.
      Proposals on the improvement of the system of preventive measures, including the
      monitoring of the epidemiological, sanitary and hygienic situation, personnel
      training, technical provision, the cooperation of different services and
      departments, capable of ensuring the liquidation of the consequences of emergency
      situations of the natural character, are made.

PMID- 14716968
TI  - [Organizational provision for the sanitary and epidemiological safety of the
      population in the regions of the Stavropol Territory affected by the flood].
AB  - Materials on the organizational provision and financing of measures taken with a
      view to ensure the sanitary and epidemiological safety in the Stavropol Territory
      in connection with the high flood of 2002 are presented. Due to the joint efforts
      of sanitary, antiepidemic and medico-prophylactic services of the Territory,
      administrative organs and institutions, as well as other relevant departments,
      not only high quality restoration works were carried out and completed in a short
      time, medical assistance was given to the victims and the appearance of mass
      infectious diseases prevented, but also the growth social tensions in the
      affected areas was averted.

PMID- 14716969
TI  - [Anti-epidemic provision for the population in emergency situations in the
      Krasnodar Territory].
AB  - Information on natural calamities, caused by hydrologically dangerous phenomena
      (high flood, tornado, mountain torrents) which took place in the Krasnodar
      Territory in summer 2002) are presented. As the result of the emergency
      situations 110 settlements with the population exceeding 116,000 inhabitants were
      inundated. At the peak of the high flood more than 36,000 homesteads were
      inundated, more than 56,000 persons had to be evacuated. The aggravation of the
      epidemiological situation in the affected settlements and in the territory as a
      whole could be prevented due to the timely planning and realization of measures
      aimed at the sanitary and epidemiological provision of the population of the
      Krasnodar Territory (the sanitation and disinfection of settlements, the campaign
      for the immunoprophylaxis of the population with respect of infectious diseases,
      etc.), unprecedented in their scope.

PMID- 14716970
TI  - [Organization of the workers of the State Sanitary and Epidemiologic Services of
      the Stavropol Territory in the period of eradication of the consequences of the
      flood in urban and rural regions of the Territory in 2002].
AB  - As the result of high flood occurring during the period of June 21-22, 2002, in
      the Stavropol Territory, 65 settlements were affected. About 200,000 inhabitants
      found themselves lacking centralized drinking water supply. From the very first
      days of the emergency situation the state sanitary and epidemiological service
      took a complex of measures aimed at the liquidation of the medico-sanitary
      consequences of the high flood, the prevention of the appearance of mass
      infectious diseases among the affected population. As the result of these
      measures, the appearance of the outbreaks of acute enteric infections, viral
      hepatitis A aggravations in malaria and other infectious diseases could be
      prevented.

PMID- 14716971
TI  - [Organization and execution of surveillance of the sanitary and epidemiologic
      situation under conditions of the emergency situation of a natural character].
AB  - The data on the work of the formations and institutions of the sanitary and
      epidemiological service of the Republic of North Ossetia-Alania under the
      conditions of the emergency situation of the natural character (high floods) in
      June 2002 and the liquidation of its consequences are presented. Experience in
      ensuring the interaction between the formations of the sanitary and
      epidemiological service on the problems connected with the realization of the
      epidemiological surveillance in the territories affected by the natural calamity
      is described.

PMID- 14716972
TI  - [Organization of measures for the prevention of infectious diseases in the
      Karachai-Chercassian Republic during a natural disaster].
AB  - Information on the character and scope of destructions and damage in the systems
      of the life provision of the population as the result of the high flood in the
      Karachai-Chercassian Republic is presented. The materials on the organization and
      realization of sanitary, hygienic and prophylactic measures, taken on the
      territory of the affected regions during the period of the liquidation of the
      emergency situation caused by of the high flood, have been summarized.

PMID- 14716973
TI  - [Epidemiologic situation in the quarantine of natural focal infections in the
      Southern Federal District].
AB  - Materials on the situation in quarantine natural focal infections (anthrax,
      plague, tularemia, brucellosis, leptospirosis, etc.) in the Southern Federal
      District are presented. Experience in the provision of the epidemic safety in the
      above-mentioned diseases, based on the systematic surveillance on the activity of
      epizootological factors on the territory of the natural foci of infections, are
      described. The causes of the possible aggravation of the epidemiological
      situation in a number of nosological forms in connection with changes in natural
      and socio-economic factors are given. The results of the realization of regional
      programs, making it possible to improve the system interaction between the
      administrative territories, services and departments aimed at ensuring the
      epidemiological safety of the region, are shown.

PMID- 14716974
TI  - [Basic activity of the Railroad Center of the State Sanitary and Epidemiologic
      Surveillance at the Vladikavkaz train station of the North Caucasus Railroad in
      the prevention of infectious diseases in an emergency situation].
AB  - The article deals with the data on the activity of the Railroad (RR) Center of
      State Sanitary and Epidemiological Surveillance at the train station of
      Vladikavkaz of the North Caucasian RR at the period of the liquidation of the
      consequences of the natural calamity in June-July 2002. In accordance with the
      situation, the scheme of the interaction with the territorial services and
      departments were worked out, the operative plans of antiepidemic measures were
      rectified, the sanitary, hygienic and bacteriological control on the quality of
      drinking water supply and foodstuffs on RR trains and stations was strengthened,
      the work on sanitary education among the personnel and passengers in the zone of
      responsibility of the RR Center of State Sanitary and Epidemiological
      Surveillance of the North Caucasian RR was activated.

PMID- 14716975
TI  - [Improvement of methods for indication of the causative agents of natural focal
      infections under conditions of emergency situations with epidemiologic
      consequences].
AB  - The improvement of the laboratory diagnostics of quarantine infections (QI) is
      aimed at obtaining the result at a shorter time, the simplification of making
      serological reactions, enhancing the specificity and sensitivity of the results
      due to the introduction of new = generation diagnostic preparations into
      practical use. The wide practical use of erythrocytic and immunofluorescent
      diagnostic preparations has shown that they cannot completely meet all
      requirements simultaneously. The optimized scheme of the indication of the
      causative agents of QI must ensure the combined use, at different stages of the
      analysis, of magneto-immunosorbents, enzyme immunoassay, as well as immuno
      suspension preparations for the simplification and acceleration of obtaining
      results with sufficient sensitivity and specificity provided.

PMID- 14716976
TI  - [Epidemiological situation on anthrax in the regions of the Southern Federal
      District in connection with the flood in June 2002].
AB  - Data on the epidemiological situation in anthrax in the regions of the Southern
      Federal District, situated in the zone of inundation, are presented. In 2002 no
      epidemic complications in anthrax were noted in the affected territories. The
      causes contributing to the appearance of anthrax cases among humans and animals
      are presented. Recommendations on the improvement of anti-epidemic measures are
      given.

PMID- 14716977
TI  - [Improvement of the method for the indication of the causative agent of anthrax].
AB  - A combined method for the indication of the causative agent of anthrax (Bacillus
      anthracis), including the preparation of the material to be tested, the exposure
      of the magneto-imunosorbent in the sample, cultivation in selective medium, DNA
      extraction with subsequent testing in the polymerase chain reaction with primers
      to genes cap, pag and chromosomal sequence Ba813, the registration and
      interpretation of results, has been developed. All determinations, including the
      preparation of samples, last not more than 6 hours. The indication of B.
      anthracis by the proposed method makes it possible not only to confirm its
      presence in the sample Under test, but also to evaluate its epidemic potential.

PMID- 14716978
TI  - [Gene typing of Bacillus anthracis strains isolated on the territory of the
      countries of the Confederation of Independent States].
AB  - Thirty eight B. anthracis strains isolated on the territory of the former USSR
      from different sources at different periods were studied by the method of the
      multilocus analysis of 6 chromosomal and 2 plasmid regions of B. anthracis genome
      with a variable number of tandem repeats. The strains belonged to 18 different
      genotypes; of these, 14 genotypes were described for the first time. The analysis
      of the genetic relationship of the strains gave grounds to suggest that on this
      territory both closely related strains and strains whose genotypes were remote
      from those peculiar to the greater part of other strains could occur. The strains
      belonging to subgroup A1a of molecular variability were "endemic" for the
      European part of the former USSR. A modification of the method of gene typing was
      proposed, which permitted it to be made without the use of an automatic
      sequencer; this made it possible to greatly widen the circle of laboratories
      where this method of research could be used.

PMID- 14716979
TI  - [Epidemiological situation on tularemia in the regions of Stavropol Territory
      affected by flood].
AB  - The data obtained in the analysis of the epidemiological situation in tularemia
      in the zone of inundation in the Stavropol Territory in 2002 are presented. The
      current systematic epidemiological surveillance, as well as the data of urgent
      epizootological and epidemiological survey in the zone of inundation permitted
      the objective prognostication of the situation in tularemia and formed the basis
      for the rational planning and realization of prophylactic measures.

PMID- 14716980
TI  - [Gene typing of infectious tularemia strains isolated from the Stavropol and
      Krasnodar Territories].
AB  - The typing of F. tularensis strains by four variable number of tandem repeats
      (VNTR) loci has been carried out. Among the strains isolated in the Stavropol and
      Krasnodar Territories seven genotypes have been detected and their spread in
      different natural foci has been analyzed. The data thus obtained suggest that the
      VNTR analysis may become an important instrument for studying the structure of
      the natural foci of tularemia and evolutionary relationships between individual
      areas of these foci.

PMID- 14716981
TI  - [Leptospirosis in the Southern Federal District of the Russian Federation].
AB  - The retrospective and operative epidemiological analysis of leptospirosis
      morbidity on the administrative territories of the Southern Federal District
      during the period of 1990-2002 was carried out. The dynamics and tendencies of
      morbidity in individual administrative units of the region were shown. Materials
      on the negative influence of the emergency situation arising in the region as the
      result of the natural calamity in summer 2002 were presented. As shown in this
      work, timely decisions on the stabilization of epidemiological situation taken at
      the period of high flood and inundation in summer 2002 in the Southern Federal
      District and their efficient execution made it possible to keep the
      epidemiological situation in leptospirosis under control.

PMID- 14716982
TI  - [Features of leptospirosis in the Krasnodar Territory].
AB  - The data on leptospirosis morbidity in the Krasnodar Territory, one of the most
      epidemiologically unsafe areas in this infectious disease in the Russian
      Federation, are presented. High morbidity registered in this territory greatly
      depends on the epidemic outbreaks appearing due to defects in the realization of
      a complex of sanitary and veterinary measures. The Krasnodar Territory is liable
      to be affected by natural calamities. In 1997 a severe outbreak of leptospirosis
      took place here in connection with the high flood. Due to timely prophylactic
      measures the epidemiological consequencies of the similar calamity occurring in
      2002 were brought to a minimum.

PMID- 14716983
TI  - [Current state of epidemiologic surveillance of natural foci of plague of North
      Caucasus].
AB  - Information on the epizootic situation in plague in the natural foci of North
      Caucasus and on the influence of a number of anthropogenic and natural factors on
      this situation is presented. The data given in this work indicate that under the
      conditions of the anthropogenic transformation of landscapes the character of the
      epizootic manifestations of plague is changed and new factors, capable of
      aggravating epidemiological situation, appear. In addition, some other factors
      must be considered, such as the insufficient financing of reliable field surveys
      at present, the impossibility of making reliable epizootological studies due to
      causes of the social character (armed conflicts), thus making it impossible to
      evaluate, with a sufficient degree of reliability, the real epizootic state of a
      number of territories and, therefore, the risk of human infection. In this
      connection the necessity to carefully plan prophylactic measures and measures
      aimed at the localization and liquidation of the probable foci of infection
      arises.

PMID- 14716984
TI  - [Situation of brucellosis in the regions of Stavropol Territory affected by the
      flood of 2002].
AB  - The emergency situation caused by inundations and high floods on the rivers in
      the affected regions exerts no direct influence on brucellosis morbidity among
      humans. Still the urgent evacuation of agricultural animals in connection with
      the natural calamity, their displacement and regrouping give grounds to
      prognosticate the deterioration of the epizootic situation in this infection in a
      number of regions of the territory where no sufficient veterinary surveillance
      has been ensured.

PMID- 14716985
TI  - [Epidemiologic situation of brucellosis in the regions of the Republic of
      Dagestan affected by the flood of 2002].
AB  - The Republic of Daghestan is at present one of the most unsafe territories in the
      Russian Federation with respect to brucellosis morbidity among humans. The
      figures of human morbidity in brucellosis grew from 3.4 per 100,000 of the
      population in 1999 to 10.5 per 100,000 of the population in 2002, thus exceeding
      the figures for the whole of Russia 15- to 20-fold. The analysis of human
      morbidity in the Kizlyar region (where the interregional regrouping of the cattle
      was made) after the natural calamity, as well a in other regions where live-stock
      was evacuated, indicated that by the end of 2002 an essential deterioration of
      the epidemiological situation took place in these regions. In view of grave
      epizootological situation and the absence of epidemiological safety in
      brucellosis in the Republic of Daghestan the sanitary, epidemiological and
      veterinary services should, together with other priority tasks in their work
      aimed at the liquidation of the emergency situation, pay greater attention to
      measures for the prevention of the spread of brucellosis.

PMID- 14716986
TI  - [Hydrological dangerous natural phenomena as cause of aggravation of an
      epidemiological situation].
AB  - Materials dealing with the specific features of the territory of Southern Russia,
      appearing as a consequence of natural, technogenic and some other factors, are
      presented. These materials indicate that, due to the high flood in summer of
      2002, a real danger of a sharp aggravation of the epidemiological situation in
      acute enteric infections, as well as other infections, arose on a vast territory.
      As the result of the timely evaluation and analysis of changes in the factors of
      the natural and social environment, occurring as the consequence of the high
      flood, prophylactic measures were urgently carried out, thus making it possible
      to prevent the aggravation of the epidemiological situation.

PMID- 14716987
TI  - [Experience in the use of a new test system for the rapid indication of the
      causative agents of campylobacter infection under the conditions of an emergency
      situation].
AB  - A new test system on the basis of magnetoimmunosorbents for the rapid indication
      of capmpylobacteriosis has been developed. Information on its use under the
      conditions of emergency situations is presented. Good prospects of this new test
      system in the study of environmental objects have been demonstrated.

PMID- 14716988
TI  - [Prevention of acute enteric infections and viral hepatitis A in a period of an
      emergency situation on the territory of the Karachai-Chercasssian Republic].
AB  - Information on the scope of destructions caused by the high flood, on the
      sanitary and hygienic situation on the affected territories of the Karachai
      Chercassian Republic is given. Materials on the organization and realization of
      prophylactic measures on the territory of the Karachai-Chercassian Republic at
      the period the natural calamity, under the conditions of a high risk of the
      appearance of an outbreak of enteric infections and viral hepatitis A are
      presented. In these materials the main trends of the work are pointed out; due to
      the timely taken and effectively carried out measures on the anti-epidemic
      protection of the population, the sanitary and epidemiological service was shown
      to prevent the aggravation of the epidemiological situation in the republic.

PMID- 14716989
TI  - [Experience in the work on prevention of infectious diseases in the Republic of
      Dagestan in 2002 in connection with a natural disaster].
AB  - Materials characterizing the sanitary and epidemiological situation in the
      Republic of Daghestan which arose as the consequence of the emergency situation
      caused by the high flood and inundation in summer 2002 are presented. The work of
      the sanitary and epidemiological service, carried out in cooperation with the
      relevant departments, on the organization and realization of measures aimed at
      preventing the deterioration of the epidemiological situation on the territories
      of the republic, affected by the natural calamity, is described. As shown in the
      presented materials, all these measures made it possible to ensure the effective
      control on the sanitary, hygienic and epidemiological situation in the republic
      and to prevent the appearance and spread of the outbreaks of infectious diseases.

PMID- 14716990
TI  - [Prevention of acute enteric infections and viral hepatitis A in the Republic of
      Dagestan in connection with the flood of 2002].
AB  - The data on the sanitary and epidemiological situation in the Republic of
      Daghestan during the period of high flood in 2002. The scope of sanitary,
      hygienic and prophylactic measures carried out during this period with a view to
      prevent the appearance of the outbreaks of acute enteric infections and viral
      hepatitis A in the Republic of Daghestan is shown.

PMID- 14716991
TI  - [Prevention of acute enteric infections and viral hepatitis A in the Republic of
      Adygeia in connection with a natural disaster].
AB  - Materials indicating the scope of destructions in the systems of life provision
      of the Republic of Adygeia as the result of the natural calamity (high flood) are
      presented. The complex of measures, carried out by the sanitary and
      epidemiological service of the Republic of Adygeia with the aim of the
      prophylaxis of infectious diseases, is described. As shown in this work, the
      appearance and spread of quarantine and mass infections, cases of food poisoning
      and lethal diseases in the inundated territories were prevented due to the
      coordination of the efforts and means of all republican services, organs and
      institutions, as well as due to their precise interaction.

PMID- 14716992
TI  - [Prevention of acute enteric infections and viral hepatitis A in the Stavropol
      Territory in connection with a natural disaster].
AB  - Materials on the organization and realization of prophylactic measures with
      respect to acute enteric infections (AEI) and viral hepatitis A (VHA) at the
      period of the liquidation of medico-sanitary consequences of the high flood are
      presented. As shown in these materials, the epidemiological surveillance on AEI
      and VHA in the areas affected by the emergency situation included the effective
      system of monitoring on these diseases. On the basis of monitoring optimum
      decisions were taken and concrete prophylactic measures were realized. This made
      it possible to detect the foci of infectious diseases in due time and efficiently
      liquidate them, as well as to prevent the development of the epidemiological
      consequences of the high flood.

PMID- 14716993
TI  - [Prevention of acute enteric infections and viral hepatitis A in the Krasnodar
      Territory appearing in connection with a natural disaster in 2002].
AB  - Materials on the sanitary and epidemiological situation in the Krasnodar
      Territory in connection with emergency situations (intensive snowfalls, heavy
      showers, high floods) in 2002 are presented. The scope of the destruction of the
      systems ensuring the life provision of the population in the affected regions of
      the territory is shown. To carry out the epidemiological surveillance on acute
      enteric infections, to make corrections of the planned prophylactic measures, as
      well as the timely solutions of problems connected with controlling the
      epidemiological situation, the daily monitoring of the level and dynamics of
      infectious morbidity in individual settlements among different age and
      professional groups, as well as the foci of infections, was established. 65 cases
      of acute enteric infection and 4 cases of viral hepatitis A were registered in
      the affected areas, which did not exceed the average morbidity figures for many
      years. A complex of sanitary, hygienic and prophylactic measures was carried out
      by the sanitary and epidemiological service of the territory, which made it
      possible to maintain human morbidity in acute enteric infections and viral
      hepatitis A in the affected areas on the sporadic level.

PMID- 14716994
TI  - [Bacteriological provision of anti-epidemic measures in the zones of a natural
      disaster in Southern Russia in 2002].
AB  - The bacteriological provision of the prophylactic and anti-epidemic measures,
      taken under the conditions of the unstable sanitary and epidemiological situation
      which arose as the result of the emergency situation due to the high flood in the
      Southern Federal District, was carried out by the efforts and means of
      microbiological laboratories forming a part of the territorial system of
      observation and laboratory control. On the whole, more than 20,000 samples of
      water supplied to the population for drinking and household use, more than 10,000
      samples of foodstuffs and cooking raw materials were examined in the Southern
      Federal District during the period of the liquidation of the medico-sanitary
      consequences of the emergency situation (June-August). To study the epidemic
      potential of the natural foci of quarantine infections and the probability of the
      spread of Bacillus anthracis from burial grounds for sick animals, the laboratory
      capacities of plague-control institutions were used.

PMID- 14716995
TI  - [Prevention of epidemiological consequences during an extreme situation caused by
      the natural disaster in the Republic of North Ossetia-Alania].
AB  - Information on the organization of interaction between different services
      responsible for restoration works, sanitary cleaning, disinfection under the
      conditions of the emergency situation is presented. The activity of the sanitary
      and epidemiological services in the areas in the Republic of North Ossetia
      Alania, affected by high flood, is described. Measures aimed at the
      epidemiological surveillance of acute enteric infections, the control of the
      quality of drinking water and foodstuffs, the bacteriological study of material
      samples taken from humans, vaccinal and phage prophylaxis have taken an important
      place in the work of the institutions of sanitary and epidemiological
      surveillance. As the result of all these measures the sanitary and
      epidemiological service has managed to prevent the aggravation of the sanitary
      and epidemiological situation in the republic.

PMID- 14716996
TI  - [Prevention of acute enteric infections and viral hepatitis A appearing in
      connection with a natural disaster in the Republic of North Ossetia-Alana].
AB  - Materials on the work of the sanitary and epidemiological service in the Republic
      of North Ossetia-Alania, aimed at the prophylaxis of acute enteric infections and
      viral hepatitis A under the conditions of the emergency situation caused natural
      calamities (inundation, high flood), are presented. The competent planning and
      operative realization of organizational, prophylactic and anti-epidemic measures
      have made it possible to keep morbidity in acute enteric infections and viral
      hepatitis A on a sporadic level.

PMID- 14716997
TI  - [Emergency situations in the Republic of Ingushetia and the prevention of their
      epidemiological consequences].
AB  - Information on the sanitary and epidemiological situation and water supply in the
      Republic of Ingushetia during the period before and after the emergency situation
      (high flood) is presented. The results of epidemiological observations on the
      territory of the Republic of Ingushetia for the period of June 22 to the end of
      the year 2002 indicate that no considerable rise in infectious morbidity, as well
      as outbreaks of natural focal infections, was noted. This suggests that, in spite
      of the complicated sanitary and epidemiological situation before the emergency
      situation (due to the vicinity of the conflict in the Chechen Republic, the
      intensive migration of the population and the presence of a large of refugees on
      the territory of the Republic of Ingushetia) and its sharp deterioration caused
      by the high flood, the timely realization of a complex of sanitary and
      prophylactic measures made it possible to avoid the wide spread of infectious
      diseases.

PMID- 14716998
TI  - [Realization of antimalarial measures in the period of eradication of the
      consequences of a flood in the Stavropol Territory in 2002].
AB  - As the result of the high flood, an increase in the area of anopheligenic water
      reservoirs occurred on the inundated territories, which created favorable
      conditions for the proliferation of Anopheles mosquitoes, the vectors of malarial
      plasmodia, thus creating the threat of the formation of the local sources of
      malaria in case of its penetration from other regions unfavorable with respect to
      this disease. In the affected towns and regions hydrotechnical measures aimed at
      decreasing the surface of anopheligenic water reservoirs, as well as measures
      aimed at the decrease in the number of the larval and imaginal stages in the
      development of mosquitoes, were taken, which made it possible to prevent the
      probable epidemiological aggravations in malaria.

PMID- 14716999
TI  - [Organization and execution of the use of disinfectants, insecticides and
      rodenticides in the period of the eradication of the medical and sanitary
      consequences of a flood in Stavropol Territory in 2002].
AB  - Materials on the organization and execution of disinfection, disinfestations and
      deratization works at the period of the liquidation of the medico-sanitary
      consequences of the high flood in the Stavropol Territory in 2002 are presented.
      Timely and full-scope treatment, carried out in the course of these works, played
      a positive role in preventing epidemiological aggravations among the affected
      population.

PMID- 14717000
TI  - [Sanitary and epidemiological provision of the personnel of the units and border
      formations of the North Caucasus Regional Command of the Border Guard Service of
      the Russian Federation].
AB  - The factors affecting the environment of servicemen doing their duties in
      connection with the task of guarding the state frontier of the Russian Federation
      are presented. The main trends in the activity of the sanitary and
      epidemiological service, carried out under regular conditions and the period of
      the liquidation of the consequences of high floods in the Southern Federal
      District in 2002 with the aim of preventing the aggravation of the epidemical
      situation, were shown to be determined, and the corresponding measures taken, in
      due time, thus making it possible to prevent the growth of morbidity in enteric
      and other infections among the personnel of the units and formations of the North
      Caucasian Regional Command of the Federal Frontier-Guard Service of the Russian
      Federation.

PMID- 14717001
TI  - [Role of the mass media in eradication of the consequences of a natural disaster
      in summer 2002 in Karachai-Chercassian Republic].
AB  - Experience in the collaboration of the Center of State Sanitary and
      Epidemiological Surveillance in the Karachai-Chercassian Republic with mass media
      at the period of the emergency situation in summer 2002 and in the use of the
      possibilities given by television, radio and the press, depending on their
      technical potential and audience, is presented. The necessity of raising the
      status of the sanitary and epidemiological service in modern society is pointed
      out, which should be achieved by elucidating the activity of this service to a
      wide public and explaining the importance of prophylactic medicine.

PMID- 14717002
TI  - ["Others are influenced, not me!" Physicians are often not aware how manipulated
      they are by drug industry].

PMID- 14717003
TI  - [Do you think your patients comply to prescribed medication?].

PMID- 14717004
TI  - [Vagina cytological screening--follow up of unsatisfactory specimens].
AB  - During the screening of vaginal cytological samples to determine the pre-stages
      of cervical cancer, some samples cannot be evaluated, usually as a result of the
      presence of inflammatory cells. In this study, we compare the clinical handling
      of these samples at two cytology laboratories at the Norra Alvsborgs Hospital,
      NAL, in Trollhattan, Sweden and the Sodra Alvsborgs Hospital, SAS, in Boras,
      Sweden. We also present a follow-up of the women involved. At the NAL, the women
      were treated with anti-inflammatory drugs and new samples were then taken after
      three months. At the SAS, on the other hand, new samples were simply taken after
      the next menstruation. The results indicate that no differences can be seen when
      it comes to the ease of evaluation.

PMID- 14717005
TI  - [Why do patients with kidney diseases end up with a heart of stone? Disturbances
      in calcium-phosphate balance and chronic inflammation important causes].
AB  - Despite rapid improvement in dialysis technology during the last 20 years the
      mortality rate is still very high in patients with end-stage renal disease
      (ESRD), and is in fact comparable to that of many cancer patients with
      metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD),
      and cardiac mortality for dialysis patients aged 45 years or younger is more than
      100-fold greater than in the general population. Recent evidence suggests that
      the high cardiovascular mortality rate in this patient population is associated
      with extensive vascular and valvular calcification. Although hyperphosphatemia
      may be the major cause of vascular calcification in this patient group it has
      been suggested that chronic inflammation also contributes to this process.
      Indeed, recent evidence suggests that inflammatory mediators, such as pro
      inflammatory cytokines and adipocytokines, may promote vascular calcification in
      vitro. Moreover, a2-Heremans Schmid glycoprotein (fetuin), an intrinsic inhibitor
      of the calcification process, is down-regulated during chronic inflammation.
      Lower levels of fetuin have recently been found to predict mortality in ESRD.
      Thus, further studies are needed to elucidate the roles of calcium-free phosphate
      binders as well as focused anti-inflammatory treatment strategies in the
      prevention of vascular and valvular calcification in ESRD.

PMID- 14717006
TI  - [A/Fujian--a changeable influenza virus which may cause problems during winter].

PMID- 14717007
TI  - [English meta-analysis on zanamivir and oseltamivir. Knowledge of effects of
      influenza agents still not sufficient].

PMID- 14717008
TI  - [Soft tissue sarcoma in the abdomen and i the true pelvis--guidelines for
      treatment].

PMID- 14717009
TI  - [A case report. Unconscious patient with neon yellow skin was intoxicated with
      dipyridamole].
AB  - A 66-year old man called for an ambulance from his home because of acute chest
      pain. When the crew arrived he was unresponsive and hypotensive. Sublingual
      nitroglycerine was given and subsequently the patient collapsed into circulatory
      failure and respiratory arrest. He was intubated and transported to the nearest
      hospital. The severe hypotension was combated with fluids and norepinephrine.
      During the next few hours his skin gradually turned intensely yellow, as did the
      urine. Acute myocardial infarction also occurred and renal failure developed. The
      cause of the neon-yellow colour was a complete mystery until a police patrol sent
      to his apartment found several empty packages of dipyridamole (Persantin Depot)
      corresponding to 34 g, an overdose seven times higher than any previous case
      reported in the literature. This drug has a distinct yellowish colour. The
      patient's condition gradually improved and he could be extubated within a week.
      Haemodialysis was needed for two weeks because of acute tubular necrosis after
      the prolonged period of hypotension, but thereafter he recovered.

PMID- 14717010
TI  - [There is evidence for good effect of rehabilitation after stroke. A literature
      review based on WHO's classification system ICF].
AB  - A literature review on the subject of rehabilitation of stroke patients is
      presented based on WHOs classification system ICF. Studies are presented
      regarding body function, activity, participation and environment, since the
      consequences of a stroke for the person effects different areas, indicating a
      need for rehabilitative efforts. Evidence based medicine has been used when
      available.

PMID- 14717011
TI  - [Medical ethics in medical education: Good for what?].

PMID- 14717012
TI  - [Dual loyalty--medical ethics in a tight corner when halcyon days are over].

PMID- 14717013
TI  - ["Every epoch handles death its own way, but the horror of death and the dead
      body seem to be universal"].

PMID- 14717014
TI  - [Centennial celebration neglected].

PMID- 14717015
TI  - [Buying kidney abroad?].

PMID- 14717016
TI  - [The best help for suicide-prone patients is psychotherapy--not antidepressive
      agents].

PMID- 14717017
TI  - [Important names missing in the Medical Society's centenary supplement].

PMID- 14717018
TI  - [Christian counseling at community health center?].

PMID- 14717019
TI  - [More about risks connected to high birth weight].

PMID- 14717020
TI  - [Vital 60 years of the Annual Meeting of the Swedish Medical Society--with a
      gasoline stain on its profile].

PMID- 14717021
TI  - Targeted therapy for lung cancer: implications for pharmacy practice.
      Introduction.

PMID- 14717022
TI  - Overview of targeted therapies for cancer.
AB  - Targeted therapies for cancer are discussed. Research into the molecular biology
      of cancer has revealed critical differences between normal and tumor cells and
      has pinpointed key processes that regulate the growth and progression of cancers.
      This has in turn allowed for the development of agents that specifically target
      these molecules and pathways, particularly those regulating the signaling
      transduction pathway that controls cell replication, differentiation, tumor
      metastasis, and apoptosis. Such novel targeted therapies include those that can
      inhibit the function of cellular growth factors or their receptors essential for
      signal transduction, block angiogenesis required for tumor growth and metastasis,
      and antisense strategies designed to suppress the expression of specific genes.
      These approaches have resulted in clinical benefit for selected tumor types, yet
      challenges remain such as determining the optimal dose and administration of
      these agents, alone or in combination with standard cytotoxic chemotherapy, and
      at what stage of disease they might have the greatest influence.

PMID- 14717023
TI  - Pharmacy practice issues with targeted therapy for lung cancer.
AB  - Drug costs and reimbursement issues for targeted therapies for lung cancer and
      how they affect pharmacy practice are discussed. Lung cancer is the most frequent
      cause of cancer death in the western world. Despite improvements in treatment
      results, less than 15% of patients survive five years after their primary
      diagnosis. Major advances in the understanding of cancer biology have led to the
      identification of several potential targets for cancer treatment. In non-small
      cell lung cancer (NSCLC) one of the most promising new targets has been the
      epidermal growth factor receptor (EGFR), which is overexpressed in most squamous
      cell subtypes and > or = 65% of adenocarcinomas and large cell subtypes.
      Gefitinib is an orally available small-molecule tyrosine kinase inhibitor that
      targets the intracellular domain of the EGFR. It has demonstrated activity and
      tolerable toxicity in patients with NSCLC. Because of its daily oral route of
      administration, patient compliance and education are of paramount importance, and
      the pharmacist plays an increasingly important role in patient management.

PMID- 14717024
TI  - Epidermal growth factor receptor-targeted therapy and symptom improvement in non
      small cell lung cancer.
AB  - Epidermal growth factor receptor-targeted therapy and symptom improvement in non
      small cell lung cancer are discussed. Non-small cell lung cancer (NSCLC) is a
      common and frequently incurable disease. Patients with advanced stage IIIB/IV
      disease, although not candidates for curative resection, can benefit from
      treatment that prolongs survival, alleviates symptoms, and reduces complications.
      While incremental advances have occurred with the use of chemotherapy and
      radiation therapy, the benefits have been largely palliative. Moreover, the
      adverse events associated with these therapies may undermine the treatment goal
      by replacing disease-related symptoms with treatment-related adverse events.
      Thus, novel, more targeted approaches are needed. Increased understanding of
      cellular and molecular biology has resulted in the development of treatments that
      selectively target key regulatory pathways and molecules involved in cell growth
      and metastasis. Gefitinib is one member of a new class of targeted anticancer
      agents known as tyrosine kinase inhibitors with activity against NSCLC. In
      clinical trials, gefitinib has produced responses in patients with relapsed or
      refractory NSCLC, reduced disease-related symptoms, and has been associated with
      improvements in quality of life. Such targeted therapy may have a significant
      impact on the treatment of patients with NSCLC.

PMID- 14717025
TI  - The effect of movement velocity and movement pattern on the reciprocal co
      activation of the hamstrings.
AB  - The effect of velocity and movement pattern (reciprocal vs. non-reciprocal) on
      the reciprocal co-activation of the hamstrings was investigated through analysis
      of the root mean square (RMS) and the median frequency (MDF) of surface
      electromyography (SEMG). Fourteen subjects performed six continuous repetitions
      of a reciprocal isokinetic movement pattern (maximal extension followed by
      maximal flexion), and six continuous repetitions of a non-reciprocal movement
      pattern (maximal extension only) at 100 degrees, 200 degrees, 300 degrees s-1,
      and 400 degrees s-1. Data were analyzed using separate 2 x 4 (movement pattern x
      angular velocity) repeated measures analysis of variance (ANOVA). No significant
      differences (p > 0.05) were noted between reciprocal and non-reciprocal movement
      patterns for RMS. However, results did reveal a velocity effect for RMS (F = 5.0,
      p < 0.01), with significant differences observed between 100 degrees s-1 and 400
      degrees s-1 (F = 9.4, p < 0.01), 200 degrees s-1 and 400 degrees s-1 (F = 9.5, p
      < 0.01), and 300 degrees s-1 and 400 degrees s-1 (F = 11.0, p < 0.001), with RMS
      values at 400 degrees s-1 being the highest. There was also a velocity effect for
      MDF (F = 8.03, p < 0.001), with significant differences observed between 100
      degrees s-1 and 300 degrees s-1 (F = 4.2, p < 0.05), 100 degrees s-1 and 400
      degrees s-1 (F = 20.2, p < 0.0001), 200 degrees s-1 and 400 degrees s-1 (F =
      15.221, p < 0.001), and 300 degrees s-1 and 400 degrees s-1 (F = 5.9, p < 0.01).
      In all cases the highest MDF values were exhibited at the lower velocities.
      Lastly, there was an interaction effect when comparing movement patterns at 400
      degrees s-1, with MDF values being significantly higher during the non-reciprocal
      movement pattern than during the reciprocal movement pattern (F = 10.9, p <
      0.01). Results indicated that during isokinetic movements, RMS and MDF activity
      of the hamstrings are altered as velocity changes. More specifically, as velocity
      increases overall hamstrings' co-activation increases and there is a shift in the
      power spectrum toward the recruitment of slower-twitch muscle fibers. Results
      also indicate that movement pattern (reciprocal vs. non reciprocal) does not
      effect appreciably SEMG activity of hamstrings' co-contraction.

PMID- 14717026
TI  - Comparison of motor unit action potentials using monopolar vs. concentric needle
      electrodes in the middle deltoid and abductor digiti minimi muscles.
AB  - Electromyography readings are analyzed noting abnormalities in the parameters of
      amplitude, duration, and number of phases. Previous studies have demonstrated
      variability between monopolar needle electrodes (MNEs) and concentric needle
      electrodes (CNEs) in regard to the above parameters. We hypothesized that a
      difference in measured parameters would be observed due to the physical
      differences between the needles. Twenty-three subjects participated in this
      study. Five readings were recorded from the middle deltoid and the abductor
      digiti minimi muscles using the MNE, and five readings were recorded using the
      CNE. A minimal isometric contraction of the tested muscle in the subjects
      dominant arm was performed. A significant difference was found in amplitudes
      recorded by the MNE and CNE in both muscles. A significant difference was found
      in the ADM, and not in the deltoid, with regard to duration. The difference found
      in the number of phases was clinically insignificant. DISCUSSION: The MNE
      detected larger amplitudes and durations because of its larger recording
      territory. The duration may also be affected by the distance between the
      active/reference electrodes.

PMID- 14717027
TI  - Electromyographic analysis of the arm muscles in "front support" exercises.
AB  - The electromyographic activity of the biceps brachii--BB (long head), triceps
      brachii--TB (long head) and deltoideus--DA (clavicular portion) muscles, during
      the going (G) and return (R) phases in "front support" exercise, as well the
      efficacy of this exercise for the development of these muscles strength were
      studied in 10 male volunteers. The values were normalized through maximum
      voluntary isometric contraction (MVIC = 100%) and statistically analyzed using
      the Friedman, DMS and Wilcoxon non-parametric test. A value of p < or = 0.05
      indicated significance (Campos, 1983). All the muscles presented higher
      electromyographic activity in the return phase of the movement. The triceps
      brachii was the muscle which had higher activity in both phases of the movement.
      It was concluded that the "front support" exercise is efficient for strength
      development mainly in the triceps brachii muscle.

PMID- 14717028
TI  - Coordination dynamics in Parkinson's disease patients and healthy subjects
      quantified by the coordination dynamics recording method and sEMG.
AB  - Coordination dynamics were measured in Parkinson's disease patients to quantify
      central nervous system (CNS) dysfunction. The low-load coordination dynamics in
      the patients were impaired by 56% for forward and 44% for backward moving in
      comparison to a control group of similar age. Exercising at higher load was only
      partly possible. When the disease preferentially affected one side of the body,
      the coordination dynamics were worse for the affected side. A dexterity test
      showed that coordination of hand and arm movements could be improved in the short
      term memory when exercising on the special coordination dynamics recording and
      therapy device. Simultaneously taken surface EMG (sEMG) showed that the motor
      pattern was impaired in the Parkinson's disease patients. sEMG recordings showed
      further that the fast fatigable muscle fibre activation was impaired. FF-type
      muscle fibres were already activated for low load in one and not at all in
      another muscle. In conclusion, coordination between motoneuron firings and
      between arm and leg movements were found to be impaired in Parkinson's disease
      patients.

PMID- 14717029
TI  - Using weights in abdominal exercises: electromyography response of the Rectus
      Abdominis and Rectus Femoris muscles.
AB  - Among persons who do regular exercises, many include abdominal exercises in their
      customary routine. For this, there are a growing variety of movements being
      created for strengthening the abdominal muscles. This work aims to know, through
      electromyography analysis, the action potencies of the supra and infra umbilical
      of the Rectus Abdominis and Rectus Femoris muscles during the execution of
      abdominal exercises with and without the addition of weights. Lying on the
      backside, seven flexing movements of the trunk--one without weight, three with 2
      Kg on the neck, elbow and chest and three with 4 Kg on the same points--were
      executed. Nine female university students between 18 and 23 years old
      participated in the study. Surface electrodes were fixed to the supra and infra
      umbilical areas of the Rectus Abdominis and Rectus Femoris muscles. The results
      showed that the utilization of weights in the abdominal exercises did not appear
      to be effective for the Rectus Abdominis muscle since greater action potencies
      were only verified in the Rectus Femoris muscle. We concluded that the
      differences observed in the RMS were not relevant to the point of indicating the
      utilization of weights to improve abdominal exercises because greater action
      potencies were only observed in the Rectus Femoris muscle.

PMID- 14717030
TI  - Extracellular potentials of myelinated and demyelinated human motor nerve fibres.
AB  - The extracellular potentials of myelinated and demyelinated human motor nerve
      fibres in an unbounded volume conductor are studied. Using our previous double
      cable models of normal and demyelinated human fibres, the spatial and temporal
      intracellular potentials are calculated in the cases of point polarization and
      adaptation of the fibres. The intracellular potentials are then used as input to
      a line source model that allows to calculate the corresponding spatial and
      temporal extracellular potentials at various radial distances in the surrounding
      volume conductor. Four fibre demyelinations (termed as internodal
      focal?systematic and paranodal focal?systematic demyelinations, respectively) are
      studied. In all investigated cases, the radial decline of the peak-to-peak
      amplitude of the extracellular potential depends on the radial distance of the
      field point and increases with the increase of the distance. The results are
      consistent with the interpretation that the considerably different spatial and
      temporal distributions of the extracellular potentials depend not only on the
      cable properties of the fibres, but on the methods of fibre stimulation. In the
      case of fibre adaptation, the temporal extracellular potentials in the normal and
      demyelinated cases correspond well with electromyograms (EMGs) from healthy
      subjects and patients with demyelinated disorders as reported in the literature.
      Simulation results indicate that the models used are rather promising tools in
      studying the main properties of compound action potentials in patients with
      demyelinated disorders which up till now have not been sufficiently well
      understood.

PMID- 14717031
TI  - Somatosensory evoked potentials for the diagnosis of proximal sensory median
      neuropathy with preserved distal sensory action potential.
AB  - A 33 year-old-man with paresthesia in first three fingers of the right hand after
      minor trauma of the arm was examined electrophysiologically. The proximal sensory
      median neuropathy was isolated which it is unusual in traumatic lesion. Motor and
      distal sensory conduction studies were normal but sensory evoked potentials
      (SEPs) were abnormal by right median nerve stimulation at the wrist level with
      decrease in amplitude of peripheral potential at the Erb's point, the cervical
      and contralateral parietal levels. This pattern, preserved distal sensory action
      potential and abnormal peripheral SEPs were suggesting the presence of proximal
      sensory block conduction without wallerian degeneration. The recovery was
      complete and fast in correlation with the absence of axonopathy.

PMID- 14717032
TI  - A new method of superficial peroneal nerve conduction studies.
AB  - Herein, we report a new method for obtaining sensory nerve conduction velocities
      (SCVs) in the distal segment of the superficial peroneal nerve (SPN). Twenty
      lower extremities from 10 normal subjects (mean age: 33.4 years) were evaluated.
      The recording electrodes were placed on the dorsal surfaces of the ankle and
      foot. We stimulated the SPNs on the anterior edge of subjects' fibulas, and
      evoked sensory nerve action potentials (SNAPs) antidromically. SCVs were
      calculated based upon the distances and the latencies. The mean SCV was 41.3 +/-
      4.3 m/s in the distal segment, which was slower than in the proximal segment
      (51.7 +/- 3.9 m/s). We were able to stimulate only the SPN with certainty. In
      conclusion, the described technique should be of clinical value in diagnosing
      peripheral neuropathy.

PMID- 14717034
TI  - [Rare vesical malformations].
AB  - Ultrasonography has radically changed the approach of these rare malformations,
      still diagnosed with difficulties in spite of modern iconography. Bladder
      anomalies may easily be discovered when associated with otherwise obvious
      malformations of genitalia. The rest must be suspected for non-specific signs as
      micturition troubles, multiple urinary tract infections, chronic renal failure.
      The abnormal bladder is the only common feature of a polymorphic spectrum of
      diseases including complete or partial duplication or septum, congenital
      diverticula, vesicovaginal fistula, agenesis and urachal anomalies. Treatment
      must be accorded to each case and it needs perfect knowledge of open and
      endoscopic bladder surgery.

PMID- 14717035
TI  - [Orchi-epididymitis].
AB  - The term orchiepididymitis encompasses inflammation of the epididymis and/or
      testis, i.e. epididymitis, orchitis, and true orchiepididymitis. Epididymitis is
      defined as inflammation of the epididymis. Young adults are predominantly
      affected, with a frequency peak between 20 and 40 years of age. The cause is
      usually an infectious agent, and the main route of access to the epididymis is
      retrograde propagation through the vas deferens. From puberty to 35 years of age,
      many cases are sexually transmitted. The main causative agents are Chlamydia
      trachomatis and Neisseria gonorrhoeae. In prepubertal children and in adults
      older than 35 years of age, epididymitis is among the commonplace genitourinary
      infections usually caused by enterobacteria. A urinary tract abnormality, most
      notably an obstruction of the distal urinary tract, is often the cause of the
      infection. Orchitis, a less common condition, is defined as inflammation of the
      testis. Again, most cases are related to an infection. Dissemination of the
      organism occurs either via the bloodstream, particularly with viruses (the most
      classic example being orchitis due to mumps) or by direct spread from a focus in
      the epididymis (producing true orchiepididymitis). In patients younger than 35
      years of age who have urethritis and suspected sexually transmitted disease,
      tetracyclines are the best agents and can be given intravenously at first if
      needed. Tetracyclines are effective not only on C. trachomatis but also on N.
      gonorrhoeae. This last agent also responds to other antimicrobials, such as
      ceftriaxone. Macrolides and second-generation quinolones are also effective on C.
      trachomatis. Typically, treatment is given for 3 weeks. Sexual partners should be
      evaluated and treated. In patients older than 35 years who have positive urine
      cultures for bacteria, urinary tract symptoms, a prior diagnosis of a urinary
      tract abnormality, or a history of a recent endourethral procedure, treatment can
      be given orally provided the symptoms are of moderate intensity. Either extra
      strength cotrimoxazole or second-generation quinolones should be used. Patients
      with severe disease should be admitted for parenteral therapy with an
      aminoglycoside and a cephalosporin in combination, followed by oral cotrimoxazole
      or a second-generation quinolone. If needed, the antibiotics should be changed
      according to antibiotic susceptibility test results.

PMID- 14717036
TI  - [Nosocomial infections in urology].
AB  - Hospital acquired infections represent a medical priority for surgeons as well as
      anesthetists and nursing staff. ANAES charged with national hospital
      accreditation program establishes protocols and objectives to be attained in
      terms of quality of care and patient satisfaction. According to available pilot
      studies, prevention of hospital acquired infections relies on surgical
      environment, preoperative patient preparation, sterilisation techniques,
      antibiotic prophylaxis and catheter care. Great improvements are under way in
      this domain and in management of multiresistant bacterial infections with a
      decrease in multiresistant kelbsiella infections. Our optimism is however
      tempered by the increase in methicillino-resistant Staphylococcus aureus (MRSA)
      infections. Many questions on nosocomial infections are still unanswered due to
      insufficient scientific evidence and difficulty in organising rigorous studies.
      Further progress will require a full involvement of hospital administrations and
      funding health organisations to provide the financial support required to
      implement preventive procedures and related architectural modifications.

PMID- 14717037
TI  - [Urologic complications of radiotherapy].
AB  - Radiation therapy is commonly used to treat pelvic or retroperitoneal cancers but
      has some impact on genito-urinary system: short-term side effects are frequent
      with usually a completed regression. However, the incidence of major
      complications is about 12% and is probably underestimated due to a long delay
      between radiation therapy and diagnosis of some adverse events such as ureteral
      strictures or fistula. Clinical follow-up must absolutely include an early
      diagnosis and treatment of radiation therapy complications such as renal
      dysfunction, ureteral stricture, ureteral fistula, chronic bladder injury,
      bladder fistula, urethral stricture, infertility or erectile dysfunction.

PMID- 14717038
TI  - [Therapeutic strategy in urinary calculi].
AB  - Most of the urinary stones are treated with ESWL. Endoscopic techniques are more
      frequently used as alternatives. Open surgery is rarely used. Laparoscopy is in
      the phase of evaluation and seems to be promising for some indications. This
      paper summarises the present strategy of urinary stones treatment.

PMID- 14717039
TI  - Temporomandibular disorders in adolescents. Epidemiological and methodological
      studies and a randomized controlled trial.
AB  - The aim of the present thesis was to investigate different aspects of
      temporomandibular disorders (TMD) and pain such as prevalence, diagnostics, and
      treatment among adolescents. The reliability of a questionnaire and the clinical
      examination and diagnoses according to the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) were assessed. Overall, we found it
      possible to assess and diagnose TMD in adolescents in a reliable way. The
      prevalence of TMD pain, gender differences, and the need for treatment were
      investigated among 864 adolescents from a Public Dental Service clinic. Seven
      percent of the subjects received a pain diagnosis according to the RDC/TMD, and
      the prevalence was higher among girls than boys. More subjects with TMD pain
      reported school absence and analgesic consumption compared to controls.
      Approximately every second subject who reported TMD pain also perceived a need
      for treatment. In an evaluation of psychosocial and dental factors, the following
      were found to play an important role in adolescents with TMD: stress, somatic
      complaints, and emotional problems. Three treatment methods were compared in a
      randomized controlled trial: brief information only, brief information and
      occlusal appliance, and brief information and relaxation therapy. In the brief
      information and occlusal appliance group, 60%--significantly more than in the
      other two groups--experienced a reduction of at least 50% in TMD pain. The
      influence of somatic and emotional stimuli was evaluated, and we found that
      adolescents with TMD pain were significantly more sensitive to not only aversive
      somatic but also pleasant somatic stimuli compared with healthy controls. The
      results suggest that not only nociceptive but also cognitive processes are
      implicated in chronic pain states in young TMD subjects. In conclusion, TMD pain
      is more common in girls than in boys and affects daily life. TMD pain in
      adolescents can best be improved by traditional treatment with occlusal appliance
      combined with brief information.

PMID- 14717040
TI  - [Prevalence of hepatitis B and C virus, HTLV-1 and HIV in type B
      lymphoproliferative syndromes in Gabon].
AB  - B lymphoproliferative disorders (B-LPD) are the most frequent types of lymphoid
      malignancies encountered in Gabon where HCV, HBV, HTLV-I and HIV are highly
      prevalent and all known for lymphotropism. Prevalences of HBs Ag, antibodies to
      HCV, HTLV-I and HIV were compared in 40 patients (21 men, 19 women; 17 < age < 75
      years) with newly diagnosed B-LPD (low grade lymphoma = 6, intermediate grade =
      21, high grade = 8: chronic lymphocytic leukaemia = 5) and 160 age and sex
      matched controls. None of the B-LPD patients had got transfusion or parenteral
      care from the onset of symptoms to the inclusion day. In the B-LPD group, 13
      patients had HBs Ag and antibodies to HCV, HIV and HTLV-1 were detected in 11, 6
      and 10 subjects. In monovariate analysis, HBs Ag, antibodies to HIV or HTLV-1
      were risk factors for B-LPD but antibodies to HCV were not associated with such
      diseases. Multivariate analysis showed only a relationship between HBs Ag and B
      LPD (OR = 3.86; IC: 1.11-13.48). In such patients, reactivation of B hepatitis by
      treatment of B-LBD may be an important concern. If a background poor immune
      system could explain both susceptibility to long standing virus carriage and
      lymphoma development, a participating action of the HBV in lymphomagenesis could
      not be excluded.

PMID- 14717041
TI  - [Seroprevalence of viral hepatitis C in polytransfused patients at Central
      University Hospital of Brazzaville].
AB  - The viral C hepatitis is a disease which is often asymptomatic but with a very
      high risk of death. A prospective survey on multitransfused patients with a high
      transfusional risk has been conducted between May 1st and September 30th, 2001 in
      the medical services of the Hospital of Brazzaville. It deals with 252 samples of
      blood taken on 132 multitransfused patients and 120 control cases who have never
      been transfused. The screening of antibodies has been performed with ELISA
      technique by using 2 sensitive tests: the monolisa anti-HCV plus version 2 (Bio
      Rad) and BIOTEC HCV a.b. Only monolisa is registered by AFSSAPS. The survey shows
      a overall seroprevalence of 13.9%: multitransfused patients: 26 out of 132
      (19.7%) and control cases 9 out of 120 (7.5%). The prevalence of anti-HCV
      antibodies is practically similar in both series. It is low among control cases
      before 20 years old, but important in this same group when the patients are
      multitransfused. It is very significant among adult control cases, indicating the
      probability of other transmission modes in this age bracket. Patients suffering
      from hemoglobinopathy (sickle cell) and from malignant hemopathy paid an heavy
      toll to the virus with respectively 16.9% and 22% of prevalence even if the
      sampling is restricted. This results point out the necessary implementation of a
      systematic screening of all the main viruses before transfusion.

PMID- 14717042
TI  - [Profile and sensitivity to antibiotics of 115 staphylococcal strains implicated
      in septicemia in a Tunisian general hospital].
AB  - Staphylococci remain among the main responsible bacteria for septicemia. The
      resistance to antibiotics already makes a prognosis difficult. We carried out a
      study on Staphylococcus isolated from blood culture on 3 years in general
      hospital in Tunisia. We present the different species and their sensitivity to
      antibiotics. S. aureus is the predominant isolated species. S. epidermidis is
      essentially isolated in newborn intensive care unit. The meticillino-resistance
      concerns 14% of the whole strains and 5.2 of the S. aureus. No resistance is
      found as regard the vancomycin and the pristinamycin; ofloxacine is inactive on
      14.8% of strains and the gentamicine on 11.3%. The resistance of staphylococci of
      our study is lower than the rates reported in southern Europe and in North
      America.

PMID- 14717044
TI  - [AIDS at Central University Hospital of Brazzaville: experience of the "Grands
      Enfants" pediatric department].
AB  - The epidemiological factors, clinical aspects and short term evolution of
      children infected by aids were assessed over a period of five years in "Grands
      Enfants" paediatric service of Brazzaville CHU. The medical reports of 81
      patients have been collected, their average age was 9 years old +/- 3.5. The HIV
      1 was the only identified virus. 59% of children's parents were divorced, and 7%
      were single. The infection transmission was vertical in 70% of cases,
      transfusional in 28% of cases and indeterminate in 1% of cases. The symptoms
      were: the impairment of body status in 90% of cases, shown by a weight loss in
      89% of cases; a long-term fever was observed in 56% of cases and a chronic
      diarrhoea was noticed in 54% of cases. The lymphadenopathies and digestive
      Candida were observed in 26% and 36% of cases. 6% of the patients had a
      psychomotor retardation. The respiratory infections and the diarrhoea were
      pathologies the most frequently noticed. The associated infections were
      essentially pulmonary tuberculosis 40% of cases, the otitis, the pneumococcal and
      cryptococcal meningia 2% of cases. The Burkitt lymphoma and the Kaposi sarcoma
      were shown in 1% of cases. The evolution was shown by a high mortality due to a
      dehydration in 59% of cases, a respiratory pathology in 22% of cases and anaemia
      in 15% of cases. This high mortality points out the problem of the treatment of
      patients, a problem increased by family poverty.

PMID- 14717043
TI  - [Epidemiology of malaria in a village of Sudanese savannah in Mali (Bancoumana).
      Anti-TRAP and anti-CS humoral immunity response].
AB  - Vaccine development research is an important component of malaria control
      strategies. Thrombospondin related anonymous protein (TRAP) and the
      circumsporozoite (CS) protein are two antigens of sporozoite surface. Immune
      response to these two antigens may contribute to the development of anti
      sporozoite vaccine. Recent studies suggest that antibodies anti-TRAP may
      partially block sporozoites penetration in hepatocyte, and thereby reducing
      malaria morbidity. We carried out a study to assess the seroprevalence of anti
      TRAP and anti-CS antibodies and to identify a possible role of these antibodies
      on malaria morbidity in children 1-9 years old living in a rural hyperendemic
      village. We performed 5 cross sectional surveys and a longitudinal follow up in
      1993 and 1994. During each cross sectional study, children were examined for
      fever and splenomegaly; all febrile children received thick film examination, and
      serologic analysis was performed in one third of these, randomly selected. The
      results show that the seroprevalence of anti-TRAP and anti-CS varied with age and
      season (p < 0.05). Association between the prevalence of anti-TRAP and
      splenomegaly was observed during two cross sectional surveys (June and October
      1993). The presence of anti-TRAP antibody was associated with Plasmodium
      falciparum infection at the beginning of the transmission season (June 1993 and
      July 1994). A negative association between the level of anti-TRAP title and
      parasitemia was observed (March and October 1994). These findings suggest no
      clear evidence of the protective role of anti-TRAP antibodies in uncomplicated
      malaria, possibly due to the limited persistence of these antibodies under
      natural situations.

PMID- 14717045
TI  - [Otorhinolaryngology pathologies and HIV/AIDS. Apropos of 19 cases].
AB  - This work is the result of a retrospective study carried out over three months,
      from February to April 2002 in the ENT service of Gabriel Toure hospital of
      Bamako (Mali). The purpose of the study was to find out the prevalence of
      HIV/aids among ENT patients over the study period. Out of 691 patients, there
      were 19 cases of seropositivity (2.7%). These seropositive patients were quite
      often young women, over half of them urban (16/19), jobless and unpaid. The oro
      pharyngo-laryngology symptoms though not often obvious in the HIV/AIDS
      manifestations deserve to be studied more as they can point out possible
      screening.

PMID- 14717046
TI  - [Application of ELISA for the quantification of Androctonus australis hector
      venom in the envenomed serum of people and rats before and after immunotherapy].
AB  - Scorpion envenomation remains an important health problem in many countries in
      the world, especially in North Africa, Asia and America. In Algeria, the most
      dangerous species for humans are Androctonus australis hector (Aah) and Buthus
      occitanus tunetanus (Bot). These scorpions are responsible for the apparition of
      various symptoms in envenomed patients such as: pain, hypertention, hypotension,
      sudation and fever. An aggravation of clinical conditions of envenomed patients
      is characterized by a pulmonary cedema and myocardial damage. The evaluation of
      the severity of scorpion envenoming by immuno-enzymatic assay requires firstly,
      the preparation of a specific anti-horse F(ab')2 peroxydase conjugate not yet
      commercialized. The restatement of conditions of ELISA sandwich test allowed its
      utilization in determination of the venom concentration in envenomed patients and
      rats sera after envenoming by scorpion venom. Standardization of this test, its
      reproductibility, linearity and its detection limit were defined. The venom
      concentrations are directly deducted from standard curves prepared by the
      dilution of Androctonus australis hector in human serum collected from healthy
      donors and in non envenomed rats serum. The present study showed that ELISA test
      has a good linear response in a range of concentrations of venom antigen. Its
      detection limit was 0.5 ng/ml of Aah venom in serum. This specific test of
      scorpion envenoming aims in one side at establishing a correlation between venom
      levels and the clinical observations and at evaluating the severity of the
      envenoming before and after immunotherapy.

PMID- 14717047
TI  - [Therapeutic approaches for omphalocele in developing countries: experience of
      Central University Hospital of Yopougon, Abidjan, Cote d'Ivoire].
AB  - A retrospective study about 80 cases of exomphalos treated in the digestive unit
      of the paediatric surgery department in Abidjan teaching hospital--Cote d'Ivoire
      had been performed to analyse the result of this malformation treatment during 8
      years. Prenatal diagnosis was made in two cases on six antenatal ultrasounds.
      Prematurity involved 7% of newborn and their birth weight ranged from 2500 to
      4000 grams in 70% of cases. Treatment began in 64% at birth, conservative
      treatment with merbromine tannage was systematic on the non disrupted exomphalos.
      Surgery was indicated in the disrupted exomphalos and in the complicated cases of
      conservative treatment. Intestinal occlusion was the main fatal complication
      observed in both treatments but most of the time it occurred with surgical
      closure. Total lethality reached 30%, influenced by exomphalos super infection
      and by neonatal resuscitation insufficient means. Authors think exomphalos
      lethality reduction implies antenatal ultrasonographic for early diagnosis which
      could indicate a possible caesarian section in case of the voluminous exomphalos
      in order to prevent disruption and neonatal resuscitation operation.

PMID- 14717048
TI  - [Misunderstood neurological side effects of amodiaquine: apropos of 35 cases in
      children at Central University Hospital of Yopougon at Abidjan, Cote d' Ivoire].
AB  - The case reports about the neurological sides effects of amodiaquine are scare,
      and just a few of them concerned the children. But more and more, amodiaquine is
      prescribed because of the resistance of Plasmodium in front of chloroquine. And,
      in the endemic area of malaria, there are more and more neurological side effects
      with amodiaquine among the children. From a retrospective study, from January
      1998 to June 2000, the authors described 35 case reports of children aged from 5
      months to 15 years who presented neurological side effects after taking
      amodiaquine in endemic malarial area. The aim of this study is, first to inform
      the pediatricians in our area about these side effects, as they are not mentioned
      in therapeutic guides. Second, it shows that it is not exceptional in the endemic
      area of malaria.

PMID- 14717049
TI  - [Epidemiology of malaria in a village of Sudanese savannah area in Mali
      (Bancoumana). 2. Entomo-parasitological and clinical study ].
AB  - We carried out five cross sectional surveys between 1993 and 1994 to assess the
      epidemiology of malaria in the village of Bancoumana, located in the Sudanese
      savannah areas of Mali. Each survey included a collection of entomological,
      clinical, parasitological and immunological data. The study population involved
      1600 children from six months to 9 years of age. The main vector was Anopheles
      gambiae s.l., man bite rate and entomological inoculation rate were maximum
      respectively in August (peak of the transmission season) and October (end of
      transmission season). Plasmodium. falciparum was the main parasite species
      observed. Spleen enlargement rate, parasite rate, gametocyte rate and parasite
      density varied significantly with age and season. The parasite rate, gametocyte
      rate and parasite density were significantly low in October 1994 compared with
      October 1993 while the entomologic parameter did not show any variation over the
      two years. This reduction of parasitologic index between 1993 and 1994 may be
      related to an increase of anti-malarial drug use in the population. Our results
      show that malaria is hyperendemic in the village of Bancoumana.

PMID- 14717050
TI  - [Agents of community acquired purulent meningitis in the child: epidemiologic
      trends in Abidjan, Cote d'Ivoire, from the year 1995 to 2000].
AB  - OBJECTIVE: To assess prevalence and trends of community acquired bacterial
      meningitis in childhood in a tertiary-care hospital before introduction of the
      HIB conjugate vaccine. STUDY DESIGN: Laboratory based data were recorded from
      January 1995 to December 2000 on two hundred and eighty seven children with
      bacterial meningitis. Identification of bacterial agents was performed with
      conventional methods. Information including age, gender, bacterial aetiology of
      meningitis, month and annual prevalence of agents was examined. RESULTS: The age
      of infected children ranges from 1 to 10 years with an average and median age of
      34.2 months and 12 months respectively. Fifty five percent of children were male.
      The overall prevalence of agents were respectively 47.8% for Streptococcus
      pneumoniae followed by Haemophilus influenzae 39% and Neisseria meningitidis
      13.2% with predominance of serogroup C. Stratification by age group shows that
      Haemophilus influenzae was the most common agent among children < 1 year of age
      following by S. pneumoniae and N. meningitidis. After 5 years, the number of
      cases of S. pneumoniae and N. meningitidis was prevalent. After 10 years, N.
      meningitidis was the first aetiology of bacterial meningitis. The six years data
      recorded highlighted the high and stable prevalence of H. influenzae B and S.
      pneumoniae and the low prevalence of N. meningitidis and high incidence of
      invasive meningococcal, pneumococcal and Haemophilus influenzae during the six
      years between September and February. CONCLUSION: Conjugated HIB vaccine is
      needed in our country to lower incidence of H. influenzae meningitis as already
      seen in developed countries. Continuous surveillance is necessary to monitor the
      disease trends, serotype distribution and antimicrobial susceptibility in order
      to implement appropriate public health interventions against community acquired
      bacterial meningitis.

PMID- 14717051
TI  - [National strategy in the battle against scorpion stings and envenomations.
      Application and evaluation].
AB  - Scorpion stings represent the first cause of poisoning with an incidence of 30 to
      50% of all declared cases in the Centre Anti Poison of Morocco (CAPM). Aware of
      this increasing problem, the CAPM paid special attention to this pathology.
      Thanks to its retrospective and prospective studies, the scorpion species mapping
      has been determined as well as the demographic features of stung patients, the
      nature and the chronology of clinical events in scorpion envenimation, and the
      epidemiological, clinical and therapeutical factors of severity. On this basis,
      the CAPM worked out a national strategy to struggle against scorpion stings whose
      aim was to decrease the morbidity and mortality caused by stings of scorpion as
      well as to rationalise economic expenses. The components of this strategy were
      based on the training of the medical and paramedical staff, on information,
      education, communication involving different sectors, on identification of needs
      and on follow-up and assessment. A nationwide campaign was implemented to change
      the population and health-care staff's behaviour regarding this pathology. Its
      evaluation permitted to improve the compilation of cases with census of 14104
      cases, to reduce lethality rate and to rationalise expenses while banishing some
      medicines and avoiding useless hospitalization.

PMID- 14717052
TI  - [Clandestine slaughtering in Tunisia: investigation on the knowledge and
      practices of butchers concerning hydatidosis].
AB  - Echinococcosis is one of the major parasitic diseases in Tunisia, accounting for
      a considerable public health problem. We propose in this work to analyse the
      behaviour of butchers and to evaluate its impact on the hydatic cyst
      transmission. MATERIAL AND METHODS: We carried out a national transversal
      descriptive survey that included 97 butcher shops using illegal practice, located
      in 18 regions (governorats) of Tunisia. The sampling procedure was implemented
      according to the level of disease endemicity. RESULTS: 60.8% of butcher shops
      were located along main roads and therefore supplying travellers. Among the
      animals slaughtered sheep come in first position (97.9%). More than 80% of the
      butchers kept aside a place around the butcher shop to sacrifice their animals.
      We noted the presence of dogs near butcher shop in 52.6% of cases and stray dogs
      in 43.3% of cases. Only 13.4% of the butchers knew the disease mode of
      transmission. Parasitized viscera were thrown into dustbins or further in the
      riverbed in 56.7%. More than 50% of butchers, having an inadequate behaviour in
      front of parasitized viscera or ignoring the disease cycle, were originating from
      an hyper or holoendemic area. CONCLUSION: Illegal slaughtering practices have an
      important impact on transmission of cystic echinococcosis in Tunisia.

PMID- 14717053
TI  - [Ecoethology of vectors and transmission of malaria in the lowland rice growing
      region of Mandritsara, Madagascar ].
AB  - To evaluate the determining factors of the malaria transmission in the northwest
      region of Madagascar, transversal studies were carried out through one year, from
      March 1997 to April 1998, in two villages located near Mandritsara, at less than
      300 meters above sea level. The rice-growing region forms an intermediate zone
      between the central highlands with epidemic and instable malaria and the coastal
      zone with endemic and stable malaria. Mosquitoes were collected when landing on
      humans during the night and by pyrethrum spray catches as regards endophilic
      mosquitoes. Three vectors were identified: Anopheles arabiensis, An. gambiae and
      An. funestus. An. arabiensis and An. gambiae were exophagic and zoophilic. An.
      funestus was endo-exophagic and anthropophilic but this species shows also a
      zoophilic trophic deviation. In both villages, An. funestus is the main vector of
      human malaria. Malaria transmission was estimated to be around 50 and 70
      infective bites/person/year in each village.

PMID- 14717054
TI  - [The mosquitoes (Diptera Culicidae) of Morocco. Bibliographic review (1916-2001)
      and inventory of the species].
AB  - The history of the Culicidae of Morocco was related from bibliographical data. A
      synthesis of the almost entire works carried out on these Insects (Diptera) since
      1916 allowed to bring out the main stages of research of which they were the
      subject, while emphasizing the important periods of large malaria epidemics in
      Morocco. A short list of species is also given.

PMID- 14717055
TI  - [Plasmodium falciparum: epidemiology and man-mosquito transmission and infection
      in the vector].
AB  - The level of malaria transmission is usually estimated by some entomological
      parameters (entomological inoculation rate or reproductive rate and its seasonal
      variations). However, only one aspect of the malaria transmission is explored by
      this way, i.e. the transmission of Plasmodium from mosquito to man. The
      transmission from man to mosquito, the development of parasite in the mosquito
      midgut, and the role of transmission blocking immunity remain poorly documented.
      Recent studies on vaccination with gamete antigens showed that transmission
      blocking immunity, and the natural infectiousness of gametocytes after treatment
      underlined the need for taking into account a new aspect of malaria epidemiology
      concerning the transmission of Plasmodium from man to mosquito. In this paper,
      authors propose and discuss different new indicators and methods to improve our
      knowledge on malaria epidemiology.

PMID- 14717056
TI  - Fatty acid composition of serum lipids: is this marker of fat intake still
      relevant for identifying metabolic and cardiovascular disorders?
AB  - Analysis of the fatty acid composition of serum lipid fractions is an old but
      still useful method for several purposes. The proportions of essential
      polyunsaturated and trans fatty acids are biomarkers of dietary intake that can
      be used to improve estimates of fatty acid intake in dietary trials and
      population studies. Furthermore, the metabolism of essential n-6 and n-3 fatty
      acids is reflected in the serum fatty acid composition. Changes in the activity
      of the delta-6 and delta-5 desaturases, which affect the proportions of
      dihomogamma-linolenic acid and arachidonic acid in serum lipids, are associated
      with insulin resistance and may explain differences in coronary heart disease
      risk.

PMID- 14717057
TI  - Plasma fatty acid composition and incidence of coronary heart disease in middle
      aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND AND AIM: To prospectively investigate the relation of plasma
      cholesterol ester (CE) and phospholipid (PL) fatty acid (FA) composition with
      incidence of coronary heart disease (CHD). METHODS AND RESULTS: 3,591 white
      participants in the Minneapolis field center of the Atherosclerosis Risk in
      Communities Study, aged 45-64 years, were studied. Plasma FA composition of CEs
      and PLs was quantified using gas-liquid chromatography and expressed as
      percentage of total FAs. Incident CHD was identified during 10.7 years of follow
      up. In both CE and PL fractions, the proportions of stearic (18:0) acid, dihomo
      gamma-linolenic (20:3n6) acid and total saturated fatty acids (SFAs) were
      significantly higher while arachidonic (20:4n6) acid and total polyunsaturated
      fatty acids (PUFAs) were significantly lower among participants who developed
      incident CHD (n = 282). After adjusting for age, gender, smoking, alcohol
      drinking, sports activity, and non-FA dietary factors, the incidence of CHD was
      significantly and positively associated with the proportion of dihomo-gamma
      linolenic acid but inversely associated with arachiadonic acid. The multiply
      adjusted rate ratios (RRs) of CHD incidence for the highest versus the lowest
      quintile were 1.31 in CE and 1.44 in PL for dihomo-gamma-linolenic acid (p for
      trend: 0.05 and 0.017, respectively), 0.59 in CE and 0.65 in PL for arachidonic
      acid (p: 0.016 and 0.024, respectively). Also significantly and positively
      associated with incident CHD were PL stearic acid and CE linolenic (18:3n3) acid.
      Only a borderline significant positive association was observed for total SFAs in
      CE (multivariate RRs across quintiles: 1.00, 1.15, 1.40, 1.62, 1.32; p = 0.07).
      Total PUFAs or monounsaturated FA were not independently associated with CHD.
      CONCLUSIONS: Our study found a weak positive association of SFAs with incident
      CHD. Our findings also confirm that FA metabolism in the body, such as the
      activity of delta-5 desaturase, which converts dihomo-gamma-linolenic acid to
      arachidonic acid, may affect the development of CHD.

PMID- 14717058
TI  - Association of birth weight and breast-feeding with coronary heart disease risk
      factors at the age of 6 years.
AB  - BACKGROUND AND AIM: It has been shown that early growth and nutrition affect
      health in childhood and later life. The aim of this study was to assess the
      association of birth weight and breast-feeding in infancy with body mass index
      (BMI) and serum lipids at the age of six years. The contributions of current
      macronutrient intake, maternal age and BMI were assessed. METHODS AND RESULTS:
      This was a longitudinal observational study of 120 randomly chosen children whose
      birth weight and duration of breast-feeding had been recorded. At the age of six
      years, their weight and height, and serum cholesterol (total, LDL and HDL) and
      triglyceride levels were measured at healthcare centres in Iceland. Dietary
      intake at six years was estimated using 3-day weighed food records. The duration
      of breast-feeding negatively correlated with BMI in 6-year-old boys (B = -0.19 +/
      0.07, p = 0.011) but not in girls; after adjusting for maternal BMI, the
      relationship in boys was of borderline significance (p = 0.087). The 6-year-old
      boys who had been breast-fed for < 6 months had a significantly higher BMI (18.0
      +/- 2.5 kg/m2) than those breast-fed for 8-9 months (15.8 +/- 1.2 kg/m2, p =
      0.006) or > or = 10 months (15.7 +/- 1.2 kg/m2, p = 0.005). A longer duration of
      breast-feeding was related to higher HDL-cholesterol levels in 6-year-old girls
      (B = 0.03 +/- 0.01, p = 0.032), but not boys. Birth weight was not related to BMI
      or serum lipid levels at the age of 6 years. CONCLUSION: In this high birth
      weight population, a longer duration of breast-feeding may be effective in
      preventing childhood overweight, at least among boys. Breast-feeding also seems
      to be related to an improved lipid profile in girls.

PMID- 14717059
TI  - A reduction in dietary saturated fat decreases body fat content in overweight,
      hypercholesterolemic males.
AB  - BACKGROUND AND AIM: The effect of the quality of dietary fat on body composition
      is unknown. Our objective was to determine whether body composition is modified
      by the isocaloric substitution of a diet rich in saturated fat by a diet high in
      monounsaturated fat (Mediterranean diet) or a carbohydrate-rich diet in
      overweight subjects with hypercholesterolemia. METHODS AND RESULTS: The study
      involved 34 hypercholesterolemic males aged 18-63 years with a body mass index
      (BMI) of 28.2 (2.6), all of whom consumed a diet rich in saturated fat (SAT) for
      28 days. They were then randomly divided into two groups of 17 subjects and
      underwent two dietary periods of 28 days each in a crossover design: a
      Mediterranean diet high in monounsaturated fat (MONO) and a carbohydrate-rich
      diet (CHO). The order of the diets was different for the two group. The CHO diet
      contained 57% CHO and 28% total fat (< 10% saturated fat, 12% monounsaturated fat
      and 6% polyunsaturated fat); the Mediterranean diet contained 47% CHO and 38% fat
      (< 10% saturated fat, 22% monounsaturated fat--75% of which was provided by olive
      oil- and 6% polyunsaturated fat). The variables measured at the end of each
      dietary intervention period were: 1) body composition by means of bioelectrical
      impedance; 2) plasma lipoproteins using enzymatic techniques; and 3) fatty acids
      in cholesterol esters by means of gas chromatography. BMI and the waist/hip ratio
      remained the same during the three dietary periods. A decrease in fat was
      observed when changing from a saturated fat diet (23.3 (6.3) kg) to a
      Mediterranean diet (20.8 (7.2) kg) (p < 0.05), or a carbohydrate-rich diet (20.6
      (6.7) kg) (p < 0.05). Lean mass increased when changing from a SAT diet (58.4
      (7.0) kg) to a CHO diet (60.2 (7.0) kg) (p < 0.05). CONCLUSION: The isocaloric
      substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich
      diet decreases total body fat in hypercholesterolemic males.

PMID- 14717060
TI  - Clinical and biochemical characterisation of patients with autosomal recessive
      hypercholesterolemia (ARH).
AB  - BACKGROUND AND AIM: Inherited hypercholesterolemias are common disorders
      characterised by elevated LDL-C levels and premature coronary heart disease. We
      have recently described a recessive form of hypercholesterolemia (autosomal
      recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because
      of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor
      (LDL-R) activity in the liver. The aim of this study was to characterise in
      detail the phenotypes of subjects with homozygous and heterozygous ARH. METHODS
      AND RESULTS: We have so far identified six Italian families with ARH and studied
      the clinical and biochemical characteristics of 11 homozygotes (age 13-47 years)
      and 12 obligate heterozygotes (age 42-83 years). The study protocol included an
      evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding
      activity, and apo E genotype; a structured questionnaire (CHD risk factors,
      medical history, current medications); a physical examination, resting and stress
      ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and
      coronary angiography. The pedigrees were characterised by the absence of vertical
      transmission; consanguinity was documented in two families. Only the two
      previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65G > A),
      were identified in the probands. All of the ARH homozygotes had large tendinous
      xanthomas, two had exertional angina, and four a positive stress ECG. None had
      experienced myocardial infarction or stroke. More than half had instrumental
      signs of atherosclerosis such as a positive stress ECG or positive carotid echo
      doppler examination. The ARH heterozygotes were consistently normal and had a
      normal lipid profile. CONCLUSIONS: The ARH phenotype resembles that of familial
      hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The
      absence of vertical transmission, and the presence of mild coronary heart disease
      and consanguinity, can suggest a possible diagnosis of ARH. ARH might be
      considered a phenocopy of FH but heterozygous subjects seem to have a
      consistently normal phenotype.

PMID- 14717061
TI  - Pulse rate in childhood: reference limits.
AB  - BACKGROUND AND AIM: Systematic quantitative resting pulse rate measurements may
      represent an additional parameter for the study of cardiovascular risk factors in
      youth as well as in adulthood. The aim of this study was to evaluate resting
      pulse rate and its distribution curve in order to define reference limits in a
      sample of adolescents from Turin, Italy. METHODS AND RESULTS: The study
      population consisted of 2230 children aged 12-18 years, who were randomly
      enrolled from Turin Junior High Schools. All of the participants underwent pulse
      rate, blood pressure and height measurements. The 5th and 95th percentiles of the
      pulse rate in boys and girls are reported by age and height. The pulse rate was
      higher in the girls, but progressively decreased with age and somatic growth in
      both genders. CONCLUSIONS: The present study provides reference blood pressure
      values by age, gender and height in a sample of male and female adolescents.

PMID- 14717062
TI  - Ins and outs of apoptosis in cardiovascular diseases.
AB  - AIM: Cardiovascular disease (CVD) is the term used to define a group of disorders
      of the heart and blood vessels. Apoptosis, also known as programmed cell death
      (PCD), is genetically programmed "cell suicide" that plays an essential role in
      physiological processes such as embryo development, synaptogenesis, tissue
      turnover and the negative selection of T-cells, as well as in many diseases, such
      as cancer, and autoimmune and neurodegenerative diseases. The aim of this paper
      is to review the most recent data concerning the role of apoptosis in CVD,
      concentrating on the key apoptotic pathways in cardiomyocytes that may represent
      potential targets for therapeutic interventions. DATA SUMMARY: The function of
      apoptosis in regulating CVD has recently been extensively investigated as a
      possible mechanism explaining the pathophysiological significance of various
      forms of CVD. Despite the difficulties of studying apoptosis in cardiomyocytes, a
      large number of studies of cellular and animal models suggest that they have the
      main apoptotic pathways that are also active in other cell types. However, the
      role of apoptosis in human pathologies, such as heart failure, ischemic heart
      disease and cardiac hypertrophy is still controversial. We revised classical
      (TUNEL) and novel experimental approaches (knock-out and transgenic mice; high
      throughput genomics and proteomics) to address the role of apoptosis in CVD,
      concentrating on potential targets for therapeutic intervention. CONCLUSION:
      Knowledge of the basic mechanisms regulating apoptosis activation and inhibition
      in cardiomyocytes may have important clinical and therapeutic implications.

PMID- 14717063
TI  - [Morphology and structure of the nictitating membrane cartilage in mammals].
AB  - In 30 species of Mammals of varying body size (from rat to elephant), the form,
      dimensions and structure of the cartilage of the third eyelid were studied. The
      cartilage is a thin lamina concave in its corneal side, usually elongated in the
      oro-aboral direction. In the most species studied the outline of the cartilage
      may be inscribed in a triangle with a oral base, a dorsal margin, a ventral
      margin and an aboral apex. A study of stained sections revealed, in more than
      half of species, the presence of elastic fibres in the aboral part of cartilage;
      these fibres are particularly numerous, but non uniformly distributed, in the
      Equidae, lion and Suidae.

PMID- 14717065
TI  - Studies on the location of the mental foramen in Turkish mandibles.
AB  - The position of the mental foramen was studied in 58 adult Turkish skulls which
      were divided into two groups according to age. A previously published method was
      used to determine the position of the mental foramen. The most common position of
      the mental foramen lies in line with the longitudinal axis passing between the
      first and second premolars. This result was in accordance with classical
      textbooks. Another measurement was also performed on the mental foramen in both
      groups. The distance between the mental foramen and the mandibular symphysis (A)
      and the distance between the mental foramen and the inferior border of the
      mandible (B) were measured. There was a significant difference between the two
      groups in B, but not in A.

PMID- 14717064
TI  - [Biometry and structure of the left internal thoracic and radial coronary
      arteries].
AB  - In an attempt to elucidate the causes of occlusion of radial arteries for
      coronary artery bypass grafts, we studied the biometry and histology of the
      coronary, radial and left internal thoracic arteries of 20 anatomical subjects
      (13 males and 7 females). These specimens were calibrated to the various bypass
      graft sites using coronary calibrators, and were then submitted to histological
      examination to determine the structure of the vessel wall. Our preliminary
      results show no correlation between the internal calibres of these various
      arteries. Like the coronary arteries and their branches, the radial artery is a
      muscular artery. In contrast, the left internal thoracic artery like the aorta,
      is an elastic artery.

PMID- 14717066
TI  - Preaortic iliac venous confluence. Marsupial vena cava. Case report.
AB  - Anomalous anatomic location of a large venous system is a very important
      assessment before aortic operations. Ours was an anatomical finding of a case of
      preaortic iliac confluence, a variation also known as 'marsupial vena cava'. As
      abdominal aortic surgery is currently performed routinely, rare anatomical
      anomalies must be spotted, in order to avoid injury to surrounding organs.

PMID- 14717067
TI  - [Topographic anatomy of the tibial nerve in the medial malleolus: application to
      the effect of nerve block anesthesia].
AB  - To better understand the anatomical variations and pathogeny of tarsal tunnel
      syndrome, the tibial nerve were dissected in 20 ankles of fresh black African
      cadavers. The tibial nerve located to 1.75 cm on average from the posterior side
      of the malleolus and to 2 cm from medial side of the calcaneus tendon. The nerve
      always ended according to dichotomic method. 90% cases of bifurcation were noted
      under the flexor retinaculum at 1 cm from the malleolo_calcaneus line; in 10% of
      dissections, we found proximal bifurcation at 5 cm from this line. The medal
      calcaneus branch which is a collateral branch of tibial nerve was constant,
      unique in 80% of cases and double in 20% of cases. The anatomical constatations
      allow a more precise anesthesia of tibial nerve block. We use constant anatomical
      marks formed by calcaneus tendon and internal malleolus tip. Olso we more
      understand the possibility of lesion of tibial nerve at the ankle during the
      synovites, or ossifications of flexor retinaculum.

PMID- 14717068
TI  - [Portal vein: echographic anatomy].
AB  - The principal descriptions of the portal vein are mainly on the results of the
      dissections of the corpses. The aim of the work was to determine the usual sizes
      of the portal vein on the alive subject by echography. From the same machine, 3
      ultrasonographers studied the anatomy of the portal vein of the volunteers
      according to a standardized methodology. The study was about 60 old people from
      11 to 82 years old, whom 31 were males (51.7%) and 29 females (48.3%). The
      transverse diameter of the portal vein, originally varied between 8 and 10 mms un
      57.9% of cases. The average was 9.05 mms +/- 2.82 and the extremes varied from 5
      to 16 mm. The transverse diameter of the portal vein, at the end varied between 8
      and 10 mms. The average was 9.16 mms +/- 2.58 and the extremes varied between 6
      and 16 mms. In 29.8% of cases, the length of the portal vein was between 61 and
      70 mms and in 8.8% between 81 and 100 mms. The average was 58.0 +/- 22.3 mms.
      Before its entry into the liver, the portal vein is divided into 3 branches in 2
      cases (3.3%). The study showed a significant change of the length of the portal
      vein according the age and sex.

PMID- 14717069
TI  - Anatomy of the celiac trunk examined by CT imaging of 104 individuals.
AB  - The diameter, length and emergence level of the celiac trunk is measured with CT
      angiography in 104 patients who have no shown abnormality in the abdomen. The
      celiac trunk emerged at T 12 level in 79.8%, at L 1 level in 14.4% and at T 11
      level in 3.8% of the patients. The mean length of the celiac artery was 6.69 +/-
      1.22 mm in the females and 7.13 +/- 1.18 in the males. The mean diameter of the
      celiac artery was 2.87 +/- 0.52 cm in the males and 2.75 +/- 0.59 in the females.
      There was no correlation between the diameter and the length. The values are in
      accordance with cadaveric studies and can be used as criteria for diagnosis of
      celiac narrowing and aneurysms.

PMID- 14717070
TI  - [Causal therapy results in good relief of symptoms in acute myeloid leukemia-
      also in the terminal phase. Good palliative care requires close cooperation with
      specialty clinics].

PMID- 14717071
TI  - [A "good death" needs to be discussed. A study of patients with acute myeloid
      leukemia demonstrates the value of palliative care].
AB  - The incidence of AML in Sweden is 5.4/100,000, i.e. 300 persons a year. About 70%
      of the patients die from their disease. In a retrospective study of medical
      journals of 106 patients with AML, who had died 1995-1997 in five selected
      hospitals in Sweden, the last week in life was studied. Sixty-six women and 40
      men (age 19-84, mean 67) were included and 658 days of care were documented. The
      cause of death, the place of death, the type of care and clinical problems and
      symptoms were registered. We found bleeding (44%), infection (71%), pain (76%)
      and respiratory (59%) and psychological (64%) problems. Next of kin were often
      present and during the last week in life 3/4 of the patients had palliative care
      focusing on symptom relief and quality of life for the patients and his/her
      family.

PMID- 14717072
TI  - [Gender perspective relevant in many medical school subjects. Essential to
      perceive men and women holistically].
AB  - Gender perspective in medicine implies that people are seen as biological as well
      as social and cultural creatures and the concept of wholeness is important.
      Still, it is common that biological explanations dominate when gender differences
      in various symptoms and disorders are discussed in medicine and medical training.
      Applying a gender perspective implies a change in that attention is then also
      paid to social conditions for men and women in various contexts, for example in
      education, on the labour market, and in different ethnic groups, parallel and
      simultaneously to biological causes. In this article it is shown that a gender
      perspective is relevant in many fields of medical training. A gender perspective
      can bring new insights in education about the healthy and diseased body,
      investigation and treatment of disease, communication and the patient-doctor
      relationship, as well as career and speciality choices. The need for education of
      teachers on gender issues is a crucial issue for those responsible for the
      academic syllabus.

PMID- 14717073
TI  - [Few and sporadic gender elements in the medical curriculum at Umea. Physicians
      play a key role when implementing suggestions for improvement].
AB  - An investigation was conducted at the medical school in Umea Sweden, to get a
      picture of the education that was offered to the students about gender and gender
      issues in medicine during the autumn of 2001. A few ambitious examples were
      reported but as a whole a gender perspective was lacking and not co-ordinated
      between courses. There was no space in the curriculum for gender theory, which
      implied that all teachers that paid attention to a gender perspective had to
      start from the beginning. They had no idea what ideas and theories had already
      been discussed. When sex or gender were focused on it was foremost biological
      aspects that were put forward while social, psychological and cultural aspects
      were not illuminated. No attention was paid to sex or gender bias. The abuse of
      women was in the curricula only three times during the five and a half years of
      medical training. Based on this inventory a proposal to develop education on
      gender issues has been outlined and approved by the faculty board.

PMID- 14717074
TI  - [Easy to remain overweight after pregnancy].
AB  - For some women pregnancy is a trigger factor for developing overweight and
      obesity. 73% of patients at the Obesity Unit, Huddinge University Hospital,
      indicated that they had retained more than 10 kg after each of their pregnancies;
      for this subgroup weight development after pregnancy was of obvious importance
      for their future health. However, in most studies mean weight retention after
      pregnancy is modest: 0.5-3.5 kg up to one year after delivery. Numerous studies
      have analysed factors explaining weight development after pregnancy and delivery,
      with a wide range of subjects, but overall it has been surprisingly difficult to
      identify strong predictors for weight development. The strongest factor is weight
      gain during pregnancy, but smoking cessation, a sedentary lifestyle and socio
      economic factors also play a role. Pregnancy and weight development are
      intertwined in a complex pattern, which includes a change in lifestyle factors,
      such as eating behaviour, physical activity, smoking cessation and degree of
      lactation, but which are still not fully understood.

PMID- 14717075
TI  - [Overweight and obesity reduce fertility of women. Weight reduction and physical
      exercise increase the chance to become pregnant].

PMID- 14717076
TI  - [High mortality in hemorrhagic stroke--new therapeutic principles should be
      tested].

PMID- 14717077
TI  - [Biobanks and the new law. Renew informed consent with moderation for tests which
      are to be used for new purposes].

PMID- 14717079
TI  - [Reduce prescription of expensive drugs without increased value].

PMID- 14717078
TI  - [Alfadil and heart failure--clinical conclusions do exist!].

PMID- 14717080
TI  - [Good and cost-effective care at county hospitals].

PMID- 14717081
TI  - [Why is there not an interest for reduced salt intake?].

PMID- 14717082
TI  - [General practitioners to be receive their pediatric training mostly at community
      health centers].

PMID- 14717083
TI  - [Should occupational environment be directed by market forces?].

PMID- 14717084
TI  - [Three cases of "air sickness"].

PMID- 14717085
TI  - [Prejudiced text on female sexuality in a psychiatric handbook].

PMID- 14717086
TI  - [Better resource allocation within health care--with focus on ethics].

PMID- 14717087
TI  - [An innovation--the bribee decides about the bribe!].

PMID- 14717088
TI  - [Lakartidningen's scrutiny routines--equal to the heavies. The peer review system
      and the expert editorial staff guarantee scientific quality].

PMID- 14717089
TI  - [A woman's weight before and during pregnancy is of importance to her infant. USA
      guidelines would benefit public health in Sweden].
AB  - This paper describes weight gain during pregnancy in Sweden in relation to
      guidelines from the United States. These guidelines take into consideration the
      fact that optimal weight gain during pregnancy is related to the woman's
      prepregnant weight in relation to her height. Almost 50 per cent of women
      delivering babies in Sweden during the year 2000 were obese or overweight. In the
      three populations studied, less than 50 per cent gained weight in accordance with
      the US guidelines, while more than 20 per cent gained less weight than
      recommended. The results indicate that, in Sweden, more attention should be paid
      to the body weight of women who bear children.

PMID- 14717090
TI  - [Overweight and obesity--a risk factor in pregnancy and labor. Increased
      frequency of abnormalities, intrauterine death and labor injuries].

PMID- 14717091
TI  - [Three cases illustrate that there are several possible explanations of
      erotomania, not only psychosis. In some of the cases autism is the basic
      problem].

PMID- 14717092
TI  - [A case report. Salmonella osteomyelitis--an unusual cause of bone destruction].

PMID- 14717093
TI  - [Bile duct injuries--x-ray examination reduces the risk but is no guarantee.
      Unconsciously wrong interpretation is avoided if two experts make the
      evaluation].

PMID- 14717094
TI  - ["Brain attack"--care during the acute phase is crucial for the long term
      outcome].
AB  - Brain attack should be considered as an urgent condition, comparable with acute
      coronary syndrome. It is important that patients with an evolving stroke should
      seek medical attention at a hospital as soon as possible in order to receive
      thrombolysis for a few, to elucidate complicating conditions and to get access to
      stroke unit care. The Scandinavian model with non-intensive stroke units and
      coordinated continuously educated multidisciplinary teams with immediate
      mobilisation and early rehabilitation reduces death, dependency and required in
      hospital days. These positive effects are independent of patient's age, sex or
      degree of brain damage. Attempts to reduce the extent of brain damage with
      neuroprotectants have so far been without success, some future strategies test
      the effects of combined thrombolysis and neuroprotectants. There is evidence that
      acute stroke patients should be monitored regularly during the acute phase aiming
      at normalized physiological conditions. This means that hypoxemia, dehydration,
      hyperthermia, hyperglycemia and hypotension should be prevented and if occurring,
      promptly corrected.

PMID- 14717095
TI  - [The sick leave boom--physician's answer to patients' existential questions?].

PMID- 14717096
TI  - [High costs of cultural diseases. Swedish fear of conflicts and focusing on
      health are breeding grounds for "epidemics" of burnout, fibromyalgia,
      hypersensitivity to electricity].

PMID- 14717097
TI  - [Hypertension, physician's honour and TV].

PMID- 14717098
TI  - [Doxazosin and heart failure: truthful information--for the sake of patients].

PMID- 14717099
TI  - [Final reply: no to the proposal concerning ombudsmen against scientific
      misconduct].

PMID- 14717100
TI  - [Comments on the PSA in primary health care: survey results in more "losers" than
      "winners"].

PMID- 14717101
TI  - [Support to involuntarily childless couples can result in 6 000 children per
      year].

PMID- 14717102
TI  - [Do we have any privileges?].

PMID- 14717103
TI  - [Free lunch and samples are not bribes].

PMID- 14717104
TI  - [Complicated drug interactions].

PMID- 14717105
TI  - Paying for life. The issues behind drug pricing.

PMID- 14717106
TI  - One for the blipper.

PMID- 14717107
TI  - Treatment activists meet with the FDA.

PMID- 14717108
TI  - Testimony on accelerated approval.
AB  - In 1994, Carlton Hogan testified before an FDA Antiviral Advisory Committee about
      the risks of letting drugs loose in the population without a rigorous method to
      detect and report late emerging toxicity. In 2003, AIDS activists met with FDA
      and repeated many of the concerns that Hogan outlined: the need for post
      marketing follow-up, the failure of drug companies to live up to commitments made
      to study drugs after they are approved, the inadequacy of penalties available to
      FDA for enforcing those commitments. Hogan's testimony seems especially prescient
      as it was made before the advent of truly effective antiretroviral therapy--and
      well before lipodystrophy and other complications associated with the new
      regimens had come to light. Carlton Hogan was an intellectual and moral leader in
      the AIDS treatment activist movement at a critical time and these excerpts from
      his testimony remain provocative today.

PMID- 14717109
TI  - World AIDS $4.7 billion--WorldCom $35 billion.
AB  - The entire worldwide campaign to save tens of millions of people is a distant
      second to the campaign to save one corporation.

PMID- 14717110
TI  - UNAIDS report for 2003: most deaths and new infections ever; some good news.
AB  - The global AIDS epidemic is still getting worse. There have been successes,
      however, and many countries are at a critical stage where they could prevent a
      major epidemic if they act now; while some are beginning to do so, others are
      not. Overall there has been a big growth in commitment by governments of rich
      countries and developing countries alike, though financially the current effort
      is only about half of what is needed. Stigma remains a major obstacle to stopping
      the spread of HIV and getting those infected diagnosed and treated.

PMID- 14717111
TI  - New neuropathy treatment guidelines.
AB  - These expert guidelines for treating neuropathic pain are particularly important,
      since most of the treatments are off label--meaning that they have been approved
      by the FDA but not for this particular purpose. These guidelines will help
      educate doctors about what treatments are best, and should also help in getting
      insurance reimbursements for care that clearly represents expert consensus but is
      not in the official labeling at this time.

PMID- 14717112
TI  - Revised U.S. adult and adolescent antiretroviral treatment guidelines; also
      revised pediatric guidelines.
AB  - Both the U.S. adult and pediatric guidelines were revised in November 2003.

PMID- 14717113
TI  - AIDS Treatment News: changes next year.
AB  - During the next year we must change our traditional business model. Also, we plan
      to do more reporting online, and continue the printed newsletter as well.

PMID- 14717114
TI  - Subscriptions to share: new way to sell content or help fundraising online.
AB  - While exploring business models for the newsletter we found a radically different
      way to sell information or help raise funds online. A system designed to
      encourage sharing allows subscribers or donors to use parts of their subscription
      to create new subscriptions for others, without the publisher's involvement-
      eliminating registration, reducing transaction costs, encouraging larger
      subscriptions or donations, and creating opportunities for bringing people
      together around an idea, purpose, or cause.

PMID- 14717116
TI  - Major trauma transfer in Western Australia.

PMID- 14717117
TI  - Hypothermic circulatory arrest techniques.

PMID- 14717118
TI  - Noninvasive detection of Simian immunodeficiency virus infection in a wild-living
      L'Hoest's monkey (Cercopithecus Ihoesti).
AB  - L'Hoest's monkey's (Cercopithecus Ihoesti) are believed to be naturally infected
      with a simian immunodeficiency virus (SIV), termed SIVIho, but only a handful of
      isolates, all derived from captive animals from the Democratic Republic of Congo
      (DCR), have thus far been characterized. Here, we report the noninvasive
      detection and molecular characterization of SIVIho in a wild L'Hoest's monkey
      from the Nyungwe Forest in Rwanda. Screening four L'Hoest's monkey fecal samples
      collected opportunistically as part of a larger noninvasive survey of SIV
      prevalence in Nyungwe National Park we identified one to be vRNA positive.
      Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of a
      subgenomic pol fragment (598 bp) identified a new SIVIho strain (RW30) that
      differed from previously reported SIVIho isolates in 17-22% of its nucleotide
      sequence. In a phylogenic tree of partial Pol protein sequences, RW30 fell well
      within the SIVIho radiation, but was not particularly closely related to any of
      the other strains. These results provide the first direct evidence that
      L'Hoewst's monkeys harbor SIVIho in the wild, that infection is prevalent in
      different areas of the species' habitat, and that geographically diverse SIVIho
      strains cluster in a single group according to their species of origin. L'Hoest's
      monkeys represent the third primate species for which the utility of noninvasive
      SIV testing has been documented.

PMID- 14717119
TI  - [Report of the 5th French-speaking virology conference, Paris, April 10-11,
      2003].

PMID- 14717120
TI  - Genetic and biological properties of HIV type 1 isolates prevalent in villagers
      of the Cameroon equatorial rain forests and grass fields: further evidence of
      broad HIV type 1 genetic diversity.
AB  - To understand the evolution of HIV-1, the genetic and biological characteristics
      of viruses that infect persons living in regions in which the virus has been
      evolving for several decades must be studied. Thus, we investigated teh genetic
      subtypes, coreceptor usage, and syncytium-inducing ability of viruses in 47 HIV-1
      infected blood samples from individuals living in rural villages in the
      equatorial rain forest and grass field regions in Cameroon. Heteroduplex mobility
      analysis (HMA) of gag (part of p24 and p7) and env (C2V5) or sequence and
      phylogenetic analysis of gag (part of p24 and p7), pol (protease), and env
      (C2V5), revealed a broad HIV-1 group M genetic diversity. Subtype analysis
      revealed genetic evidence of seven subtypes (A, C, D, F, G, H, and J) and three
      circulating recombinant froms (CRFs) (CRF01_AE, CRF02_AG, and CRF11_cpx). Only 15
      (32%) of the 47 samples analyzed revealed a concordant subtype in all three genes
      (gag, pol, and env), while discordant subtypes and CRFs were identified for the
      remaining 32 (68%) samples. Two patterns of HIV-1 diversity could be discerned in
      two provinces. While more concordant subtypes in gag, pol, and env genes were
      identified in villages of South province (10 of 13, 77%), the HIV-1 diversity in
      the West province was characterized by intersubtype recombinants (63%). Five new
      intersubtype recombinants were identified including Agag Jpol Genv, Ggag Upol
      Aenv, AGgag Jpol Aenv, Agag AGpol Henv, and Cgag AGpol AGenv. All of the 40
      viruses tested used the R5 coreceptor, of which four also used the X4 coreceptor.
      Four viruses were able to induce syncytia in MT-2 cells, however, syncytium
      induction did not correlate with coreceptor usage. This study further reveals the
      complexity of HIV-1 infection in rural Cameron and points to the future of the
      global epidemic, which may be characterized by more genetically diverse viruses.

PMID- 14717123
TI  - HFMA chapters--the heart of the association.

PMID- 14717121
TI  - Out of her own pain, she gave a voice to others.

PMID- 14717124
TI  - The Resource Center--information for healthcare financial professionals.

PMID- 14717125
TI  - The healthcare financial manager's library.

PMID- 14717126
TI  - HFMA newsletters help you find solutions.

PMID- 14717127
TI  - Wolf-Schindler gastroscope.

PMID- 14717128
TI  - Endoscopic colorectal cancer screening: screening modality versus screening
      interval.

PMID- 14717129
TI  - Anal sphincter injury following forceps delivery.

PMID- 14717130
TI  - Literature around the world.

PMID- 14717131
TI  - 2004 HFM resource guide. Vendor listing.

PMID- 14717132
TI  - Who's special?

PMID- 14717133
TI  - On Biological and Social Interfaces in Prosthodontics. Proceedings of an
      International Symposium. Toronto, Ontario, Canada, November 3-6, 2002.

PMID- 14717134
TI  - Mentoring for the CRA.

PMID- 14717135
TI  - Expecting the unexpected.

PMID- 14717136
TI  - The mystery of perceptions.

PMID- 14717138
TI  - Bibliography of journal articles (July to December 2002).

PMID- 14717137
TI  - Prognosis of colorectal cancer patients with elevated endothelin-1
      concentrations.
AB  - AIM: Prognostic indicators from clinical, laboratory and pathological data of
      patients with colorectal cancer are essential to identify high-risk groups in
      whom adjuvant therapy could be beneficial. Endothelin-1 (ET-1), a growth factor,
      has been associated with the development and spread fo solid tumours. This
      prospective study was performed to determine whiter preoperative plasma big ET-1
      concentrations might be useful as a prognostic indicator in patients with
      colorectal carcinoma. METHODS: Overall, 65 consecutive patients with colorectal
      cancer confirmed by biopsy were include prospectively in this study from 1998 to
      2001. Plasma samples from a peripheral vein were obtained prior to surgery.
      Univariant analysis of survival used age (less than or more than 70 years),
      gender, Dukes' stage (A/B vs C), tumour size (less than or more than 50 mm),
      vascular invasion, and plasma big ET-1 concentrations, and significant factors
      were then analysed using a Cox regression model. RESULTS: Three variables, age,
      Dukes' tumour stage and plasma big ET-1 concentration, and prognostic
      significance (p < 0.05). Factors associated with a poorer prognosis were age more
      than 70 years (p = 0.02), Dukes' C (p = 0.04) and plasma big ET-1 concentration
      more than 4.2 pg/mL (p = 0.02). The Cox regression model identified the same
      three variables as having independent prognostic value for overall survival.
      CONCLUSION: Preoperative plasma big ET-1 concentration may be useful in
      predicting overall survival in patients with colorectal cancer. Plasma big ET-1
      concentrations may be useful in the selection of high-risk, lymph node-negative
      patients with colorectal cancer for adjuvant therapy.

PMID- 14717139
TI  - Performance improvement tips and strategies.

PMID- 14717140
TI  - How far has healthcare come since "to err is human"? Exploring the use of medical
      error data.

PMID- 14717141
TI  - Quality concerns in assisted living facilities.

PMID- 14717142
TI  - Advancing quality improvement through using the best evidence to change practice.

PMID- 14717143
TI  - Value of the internet in achieving and sustaining quality.

PMID- 14717144
TI  - Using the Ottawa Model of Research Use to implement a skin care program.
AB  - Addressing skin care issues requires a systematic and comprehensive approach. We
      used the pragmatic Ottawa Model of Research Use to guide the implementation of
      clinical practice guidelines in a surgical program of a tertiary care hospital.
      Assessments were made of existing clinical practice guidelines, the practice
      environment, and the potential adopters. With this information, we tailored
      strategies to address the barriers and to implement the guidelines. A formative
      evaluation demonstrated positive results.

PMID- 14717145
TI  - Nurse staffing, care delivery model, and patient care quality.
AB  - Little research has been conducted examining the linkages between nurse staffing
      and care delivery models in relation to patient care quality. Nurses in this
      study perceive that an all-RN staffing model is associated with better quality
      outcomes for patients, and that staffing models that include professional and
      unregulated staff may pose a challenge for unit-based communication and the
      coordination of care. Patient care delivery models were also important predictors
      of the quality outcomes studied.

PMID- 14717146
TI  - Frequency and timing of activated clotting time levels for sheath removal.
AB  - Guidelines currently exist that describe the medical management of patients
      undergoing percutaneous coronary interventions (PCI), but these guidelines do not
      include nursing management of the patient post procedure. The nursing staff on an
      intermediate care unit believed there were numerous and unnecessary activated
      clotting time (ACT) levels obtained on post PCI patients. The purpose of this
      study was to identify the most appropriate time to begin analyzing ACT levels.
      Results from a retrospective chart audit of 44 patients indicated that 3 hours
      after the last dose of heparin, only 7% of the patients met the criteria of ACT <
      150 seconds in order to have their femoral sheaths removed, and 21% of patients
      had an ACT of < 160 seconds. It is recommended that current standard orders be
      changed to begin drawing ACT levels at 3 hours post last heparin dose and
      removing sheaths when ACT is < 160 seconds. This change would save the hospital
      nearly dollars 5000 in nursing time alone.

PMID- 14717147
TI  - ANA nurse sensitive quality indicators for long-term care facilities.
AB  - Nurse sensitive quality indicators, developed through the American Nurses
      Association's (ANA) Safety and Quality Initiative, are key to evaluating the
      quality of patient care in acute care settings. This study found that the ANA
      quality indicators were also relevant for long-term care facilities. Long-term
      care facilities can be part of the ANA Safety and Quality Initiative by
      collecting and reporting nurse sensitive quality indicators and submitting data
      to the National Database of Nursing Quality Indicators.

PMID- 14717148
TI  - Developing a residential care facility version of the observable indicators of
      Nursing Home Care Quality Instrument.
AB  - The last decade has seen a substantial growth in the development of residential
      care facilities (assisted living facilities). Evaluation of the quality of care
      in this service delivery sector has been hampered by the lack of a consensus
      definition of quality and the lack of reliable instruments to measure quality.
      Founded on extensive research on nursing home care quality, a field test of the
      Residential Care Facility Version of the Observable Indicators of Nursing Home
      Care Quality Instrument was conducted in 35 residential care facilities in
      Missouri. Content validity of the 34 items was rated by 4 expert raters as 3.4 on
      a 4-point scale of relevance. Test-retest was 0.94, interrater reliability was
      0.73, and internal consistency was 0.90 for the total scale, indicating excellent
      results for initial field-testing. A focus group confirmed the 5 dimensions of
      quality of care measured by the instrument as important in residential care
      settings.

PMID- 14717149
TI  - Is rehabilitation associated with change in functional status among nursing home
      residents?
AB  - Assessing functional status of residents in nursing homes is one way to evaluate
      the quality of care provided. The purpose of this study was to investigate
      whether rehabilitation interventions could lead to improved functional
      independence. A prospective study was carried out to examine the change in
      activities of daily living (ADL) of 310 residents aged 65 or above over a period
      of 6 months. About 41.3% (n = 128) received rehabilitation therapy. Functional
      improvement was observed in 30.6% of the participants. The corresponding figures
      for stabilization and functional decline were 45.2% and 24.2%, respectively.
      Using a multinomial logistic regression, we found that factors significantly
      associated with change in functional status included baseline ADL score, family
      visit, number of beds in the institution, and transfer to acute hospitals. After
      adjusting for these confounding variables, change in functional status of those
      who received rehabilitation and those who did not was not significantly
      different.

PMID- 14717150
TI  - An interdisciplinary approach to transitioning ventilator-dependent patients to
      home.
AB  - Home mechanical ventilation was once a remote idea and thought to be used only in
      extreme cases. However, patient preference as well as limited financial resources
      to care for these patients in a long-term setting is forcing acute care
      facilities and families to make the choice of home care. This article describes
      how an interdisciplinary team used a quality process to develop and implement
      tools to assist with discharge planning in this complex patient population.

PMID- 14717151
TI  - Storytelling: a tool for leadership to shape culture...listen to nurses' stories.

PMID- 14717152
TI  - New nurses' perceptions of nursing practice and quality patient care.
AB  - During this time of nursing shortages, hospitals that want to maintain the
      competitive edge must seek ways to recruit and retain a competent nursing staff.
      This study was conducted in a large hospital that strives to be the primary
      health care provider and employer of choice in its geographic region. The purpose
      of the study was to assess new nurses' perceptions of nursing practice and their
      expectations for meeting professional goals. Sixty-seven new nurses from 13
      hospital departments were interviewed. Comprehensive orientation, continuing
      education, and mentoring were important values identified by this group of
      nurses. Communication with physicians and fear of causing accidental harm to
      patients were expressed concerns. Data from this survey will be used by the
      organization to change orientation policies to better meet the needs of the
      nursing staff and improve recruitment and retention of nurses.

PMID- 14717153
TI  - Manure-borne estrogens as potential environmental contaminants: a review.
AB  - Livestock wastes are potential sources of endocrine disrupting compounds to the
      environment. Steroidal estrogen hormones such as estradiol, estrone, and estriol
      are a particular concern because there is evidence that low nanogram per liter
      concentrations of estrogens in water can adversely affect the reproductive
      biology of fish and other aquatic vertebrate species. We performed a literature
      review to assess the current state of science regarding estrogen physicochemical
      properties, livestock excretion, and the fate of manure-borne estrogens in the
      environment. Unconjugated steroidal estrogens have low solubility in water (0.8
      13.3 mg L(-1)) and are moderately hydrophobic (log Kow 2.6-4.0). Cattle excrete
      mostly 17alpha-estradiol, 17beta-estradiol, estrone, and respective sulfated and
      glucuronidated counterparts, whereas swine and poultry excrete mostly 17beta
      estradiol, estrone, estriol, and respective sulfated and glucuronidated
      counterparts. The environmental fate of estrogens is not clearly known.
      Laboratory-based studies have found that the biological activity of these
      compounds is greatly reduced or eliminated within several hours to days due to
      degradation and sorption. On the other hand, field studies have demonstrated that
      estrogens are sufficiently mobile and persistent to impact surface and
      groundwater quality. Future research should use standardized methods for the
      analysis of manure, soil, and water. More information is needed about the types
      and amounts of estrogens that exist in livestock wastes and the fate of manure
      borne estrogens applied to agricultural lands. Field and laboratory studies
      should work toward revealing the mechanisms of estrogen degradation, sorption,
      and transport so that the risk of estrogen contamination of waterways can be
      minimized.

PMID- 14717154
TI  - Occurrence and fate of macrolide antibiotics in wastewater treatment plants and
      in the Glatt Valley watershed, Switzerland.
AB  - An analytical method was developed for determining macrolide antibiotics in
      treated wastewater effluents and in ambient water based on solid-phase extraction
      and LC/MS analysis as well as on LC/MS/MS for structural confirmation. In
      wastewater treatment plants (WWTPs) macrolides are only partly eliminated and can
      therefore reach the aquatic environment. In treated effluents from three WWTPs in
      Switzerland, clarithromycin, roxithromycin, and erythromycin-H2O, the main
      degradation product of erythromycin, were found. The most abundant,
      clarithromycin, reflects the consumption pattern of macrolide antibiotics. Summer
      concentrations of clarithromycin varied between 57 and 330 ng/L in treated WWTP
      effluents. In the WWTP Kloten-Opfikon seasonal differences revealed a load two
      times higher in winter than in summer. The higher abundance of erythromycin-H2O
      in the effluent of WWTP Kloten-Opfikon can be explained by distinct consumption
      patterns due to the main international airport of Switzerland in the catchment
      area. In the Glatt River clarithromycin reached concentrations of up to 75 ng/L.
      Mass flux determinations in treated effluents and in river water in the Glatt
      Valley watershed showed that elimination of clarithromycin along the river
      stretch of 36 km is insignificant (<20%). Investigations in the Glatt River
      before and after the diversion of the largest WWTP revealed an observable
      decrease in clarithromycin loads.

PMID- 14717155
TI  - Size-dependent mixing characteristics of volatile and nonvolatile components in
      diesel exhaust aerosols.
AB  - Mixing characteristics of particles of different volatilities from a diesel
      engine were studied with two tandem differential mobility analyzers (TDMAs) and
      an aerosol particle mass analyzer (APM). In both TDMA systems, a heater was
      located in the aerosol path between the first and second DMAs. Diesel exhaust
      particles that were size-selected in the first DMA were passed through the
      heater, and the change in particle size due to loss of volatile components was
      determined by the second DMA. On the basis of the volatility measurements, the
      particles could be separated into two overlapping modes that varied in peak
      diameter and magnitude depending on the engine operating conditions. Particles in
      the smaller size mode were almost completely volatile, while those in the larger
      size mode contained a nonvolatile core. The TDMA data inversion technique used
      here allowed accurate determination of the mixing ratios of the two types of
      particles. These data were in turn used to validate a simple fitting method that
      uses two log-normal curves to obtain the mixing ratios. In some experiments, the
      APM was used downstream of a TDMA to directly measure the particle mass loss due
      to evaporation. The loss determined bythe TDMA-APM system was significantly
      greater than that calculated from mobility size changes measured solely with the
      TDMA. The TDMA-APM results were used to calculate the size-dependent mass
      concentrations of volatile and nonvolatile components for particles in the size
      range from 70 to 200 nm.

PMID- 14717156
TI  - Temporal trend studies on tetra- and pentabrominated diphenyl ethers and
      hexabromocyclododecane in guillemot egg from the Baltic Sea.
AB  - Guillemot eggs from the Baltic Sea, sampled between 1969 and 2001, were analyzed
      for tetra- and pentabromodiphenyl ethers (2,2',4,4'-tetraBDE (BDE-47),
      2,2',4,4',5-pentaBDE (BDE-99), and 2,2',4,4',6-pentaBDE (BDE-100)), and
      hexabromocyclododecane (HBCD). This temporal trend study indicates that the
      concentrations of the polybrominated diphenyl ether compounds increased from the
      1970s to the 1980s, peaking around the mid- to the late-1980s. These peaks are
      then followed by a rapid decrease in concentrations during the rest of the study
      period, with the concentrations of the major BDE congener below 100 ng/g lipid
      weight at the end of the period. This corresponds to less than 10% of its peak
      values. The concentrations of HBCD show a different pattern over time. After a
      peak in the middle of the 1970s followed by a decrease, the concentrations
      increased during the latter part of the 1980s. During the recent 10-yr period no
      significant change has occurred, and the annual mean concentrations are more or
      less stable at a higher level as compared to the beginning of the study period.

PMID- 14717157
TI  - Destruction of the World Trade Center and PCBs, PBDEs, PCDD/Fs, PBDD/Fs, and
      chlorinated biphenylenes in water, sediment, and sewage sludge.
AB  - Ash-laden runoff samples collected near Ground Zero soon after the September 11,
      2001 attack on the World Trade Center (WTC) and subsequent fire demonstrate the
      release of polychlorinated biphenyls (PCBs), polybrominated dipheyl ethers
      (PBDEs), polybrominated dibenzo-p-dioxins and polybrominated dibenzofurans
      (PBDD/Fs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      (PCDD/Fs), and tetra- and pentachlorinated biphenylenes (PCBPs) from the
      incident. Relative abundances of PCDD/F congeners in the runoff water and post
      disaster lower Manhattan dust samples were different from those seen in pre
      disaster NYC combined sewer outfall (CSO) samples. The WTC-related samples showed
      a greater relative abundance of 2,3,4,7,8-PeCDF than usually seen in CSOs,
      sludges, and treated wastewaters. This congener may be associated with certain
      types of incineration. Comparison of sediment and water samples collected in the
      lower Hudson River before and shortly after September 11, 2001 (9/11) showed no
      changes in PCB or PCDD/F concentrations or homologue profiles determined down to
      the parts per quadrillion range. Comparisons of ambient water samples collected
      post-9/11 with archived samples suggest that the WTC disaster did not
      significantly impact ambient concentrations of the target chemicals. Ambient
      concentrations of PBDD/Fs in New York Harbor are similar to those of PCDD/Fs,
      suggesting that these contaminants deserve increased scrutiny with respect to
      toxicity, sources, and fate in the environment.

PMID- 14717158
TI  - Model of microbial transport and inactivation in the surf zone and application to
      field measurements of total coliform in Northern Orange County, California.
AB  - The classic model of pollutant transport in the surf zone of a long, sandy beach
      developed by Inman et al. (J. Geophys. Res. 1971, 76, 3493) is altered to account
      for first-order pollutant inactivation in an effort to understand how rip cell
      dilution and bacterial inactivation control the length of shoreline adversely
      impacted by microbial pollution from a point source. A dimensionless number gamma
      dictates whether physical processes (dilution of microbes in the surf zone by rip
      cell mixing) or biological processes (microbial inactivation) control the
      distribution of pollution along the shoreline. Estimates of gamma for beaches in
      Northern Orange County, California, indicate that dilution is the primary factor
      controlling total coliform levels surrounding two drains that release nuisance
      runoff directly onto the beach. It is also shown that, even when alongshore
      currents are fast, pollutant levels will drop e-fold at distances under 4000 m
      from the point source due to dilution alone. Because dilution is ultimately
      controlled by wave climate and shoreline morphology, the results suggest the
      strategic position of drains and other point sources in high dilution wave
      environments will reduce potential adverse effects on beach water quality. In
      addition, the results stress the importance of understanding hydrodynamics when
      conducting microbial source tracking at wave-dominated marine beaches.

PMID- 14717159
TI  - Watershed vulnerability to herbicide transport in northern Missouri and southern
      Iowa streams.
AB  - Herbicide contamination of streams has been well documented, but little is
      currently known about the specific factors affecting watershed vulnerability to
      herbicide transport. The primary objectives of this study were (1) to document
      herbicide occurrence and transport from watersheds in the northern
      Missouri/southern Iowa region; (2) to quantify watershed vulnerability to
      herbicide transport and relate vulnerability to soil properties; and (3) to
      compute the contribution of this region to the herbicide load of the Missouri and
      Mississippi Rivers. Grab samples were collected under baseflow and runoff
      conditions at 21 hydrologic monitoring stations between April 15 and July 15 from
      1996 to 1999. Samples were analyzed for commonly used soil-applied herbicides
      (atrazine, cyanazine, acetochlor, alachlor, metolachlor, and metribuzin) and four
      triazine metabolites (deisopropylatrazine, deethylatrazine, hydroxyatrazine, and
      cyanazine amide). Estimates of herbicide load and relative losses were computed
      for each watershed. Median parent herbicide losses, as a percentage of applied,
      ranged from 0.33 to 3.9%; loss rates that were considerably higher than other
      areas of the United States. Watershed vulnerability to herbicide transport,
      measured as herbicide load per treated area, showed that the runoff potential of
      soils was a critical factor affecting herbicide transport. Herbicide transport
      from these watersheds contributed a disproportionately high amount of the
      herbicide load to both the Missouri and Mississippi Rivers. Based on these
      results, this region of the Corn Belt is highly vulnerable to transport of
      herbicides from fields to streams, and it should be targeted for implementation
      of management practices designed to reduce herbicide losses in surface runoff.

PMID- 14717160
TI  - Estimation of primary and secondary particulate matter intake fractions for power
      plants in Georgia.
AB  - Air pollution benefit-cost analyses depend on dispersion models to predict
      population exposures to pollutants, but it is difficult to determine the
      reasonableness of the model estimates. This is in part because validation with
      field measurements is not feasible for marginal concentration changes and because
      few models can capture the necessary spatial and temporal domains with adequate
      sophistication. In this study, we use the concept of an intake fraction (the
      fraction of a pollutant or its precursor emitted that is eventually inhaled) to
      provide insight about population exposures and model performance. We apply
      CALPUFF, a regional-scale dispersion model common in health benefits assessments,
      to seven power plants in northern Georgia, considering both direct emissions of
      fine particulate matter (PM2.5) and secondarily formed ammonium sulfate and
      ammonium nitrate particles over a domain within 500 km of Atlanta. We estimate
      emission-weighted average intake fractions of 6 x 10(-7) for primary PM2.5, 2 x
      10(-7) for ammonium sulfate from SO2, and 6 x 10(-8) for ammonium nitrate from
      NOx, with no effect of SO2 on ammonium nitrate. To provide insight about model
      strengths and limitations, we compare our findings with those from a frequently
      applied source-receptor (S-R) matrix. Using S-R matrix over an identical domain,
      the corresponding intake fractions are 5 x 10(-7), 2 x 10(-7), 3 x 10(-8), and -2
      x 10(-8), respectively, with the values approximately doubling if the domain is
      expanded to cover the continental United States. Evaluation of model assumptions
      and comparison of past intake fraction estimates using these two models
      illustrates the importance of assumptions about the relative concentrations of
      ammonia, sulfate, and nitrate, which significantly influences ammonium nitrate
      intake fractions. These findings provide a framework for improved understanding
      of the factors that influence population exposures to particulate matter.

PMID- 14717161
TI  - Ambient silver concentration anomaly in the Finnish Arctic lower atmosphere.
AB  - Mean silver concentrations in weekly particle samples collected at Kevo, northern
      Finland, were determined for the period of October 1964-March 1978 by neutron
      activation analysis. Two distinct periods were observed in the silver
      concentration levels over this time frame. During 1964-1970, mean weekly silver
      concentration levels were found in the range of 0.01-190 ng/m3 with an arithmetic
      mean of 2.19 ng/m3. A few very high silver concentration levels (>10 ng/m3) were
      observed in this period, some of which simultaneously occurred with some of the
      highest bromine and iodine concentration levels. During 1971-1978, silver
      concentration levels were in the range of 0.02-0.89 ng/m3 with a mean value of
      0.09 ng/m3. The observed concentration levels in the later period matched well
      the data from the early 1990s reported at Sevettijarvi, northern Finland, about
      60 km east of Kevo. Data analysis, historical records for this region, and
      residence time analysis (RTA) using wind back-trajectories show that occasional
      smelting of silver-rich Norilsk ores at the Nikel smelter, Kola Peninsula, was
      probably a significant contributor to elevated mean silver concentration levels
      during 1964-1970. RTA alone was not able to unambiguously identify the most
      probable source region for highest silver impacts at Kevo due to the weekly
      integrated nature of the samples collected. Critical examination of wind back
      trajectories (24 per day) for specific high silver, bromine, and iodine
      concentration weeks was carried out to supplement the ensemble RTA analysis (2
      back-trajectories per day). The supplemental back-trajectory analysis revealed
      that deposition of the smelter component silver as well as the sea components
      (bromine and iodine) could occur together at Kevo during these weekly sampling
      periods. The study implies that data from weekly integrated samples are
      insufficiently time-resolved for RTA methods alone to unambiguously resolve the
      sources contributing to ambient atmospheric concentrations at Kevo, Finland.

PMID- 14717162
TI  - Perfluorinated chemicals infiltrate ocean waters: link between exposure levels
      and stable isotope ratios in marine mammals.
AB  - This is the first study to report on concentrations of perfluorinated
      organochemicals (FOCs) in marine mammals stranded along the southern North Sea
      coast in relation to stable nitrogen and carbon isotope ratios (delta15N and
      delta13C). The presence of FOCs in top predators such as marine mammals would
      indicate a potential biomagnification of these compounds and their widespread
      occurrence. Liver and kidney tissues of nine marine mammal species have been
      sampled. Among all the measured FOCs compounds, PFOS (perfluorooctane sulfonate)
      was predominant in terms of concentration. The highest PFOS concentrations were
      found in the liver of harbor seal compared to white-beaked dolphin, harbor
      porpoise, gray seal, sperm whale, white-sided dolphin, striped dolphin, fin
      whale, and hooded seal. PFOS concentrations differed significantly between sexes
      and age classes in harbor porpoises. Stable isotope measurements (delta13C and
      delta15N) were used in this study to describe the behavior of contaminants in
      food webs. We found a significant (p < 0.05) linear relationship between PFOS
      concentrations in livers of harbor porpoises and both muscle delta13C and
      delta15N measurements. Harbor and gray seals and white-beaked dolphin, which
      displayed the highest trophic position, contained the highest PFOS levels, while
      offshore feeders such as sperm whales, fin whales, striped dolphin, and white
      sided dolphin showed lower PFOS concentrations than inshore species.

PMID- 14717163
TI  - Sources and variations of mercury in tuna.
AB  - While the bulk of human exposure to mercury is through the consumption of marine
      fish, most of what we know about mercury methylation and bioaccumulation is from
      studies of freshwaters. We know little of where and how mercury is methylated in
      the open oceans, and there is currently a debate whether methylmercury
      concentrations in marine fish have increased along with global anthropogenic
      mercury emissions. Measurements of mercury concentrations in Yellowfin tuna
      caught off Hawaii in 1998 show no increase compared to measurements of the same
      species caught in the same area in 1971. On the basis of the known increase in
      the global emissions of mercury over the past century and of a simple model of
      mercury biogeochemistry in the Equatorial and Subtropical Pacific ocean, we
      calculate that the methylmercury concentration in these surface waters should
      have increased between 9 and 26% over this 27 years span if methylation occurred
      in the mixed layer or in the thermocline. Such an increase is statistically
      inconsistent with the constant mercury concentrations measured in tuna. We
      conclude tentatively that mercury methylation in the oceans occurs in deep waters
      or in sediments.

PMID- 14717164
TI  - Analysis of sources of dioxin contamination in sediments and soils using
      multivariate statistical methods and neural networks.
AB  - Multivariate statistical methods and neuronal networks were used to evaluate the
      concentration dioxin patterns of a large data set (407 samples) in order to
      identify the dioxin sources of contaminated waters (sediment and suspended
      particulate matter samples). The evaluations indicated that a considerable
      proportion of the dioxin contamination of the river Elbe in the section between
      the Mulde tributary and the North Sea and their flood plains (soil samples) and
      the Port of Hamburg was caused by pollution originating from the Bitterfeld
      region, an industrial area of the former German Democratic Republic. The dioxin
      patterns of sediment samples from tributaries of the river Elbe in the Bitterfeld
      area itself are similar to dioxin patterns that can be attributed to metalworking
      processes. The dioxin patterns of the Hamburg inner city waters could be
      attributed to "incineration" dioxin sources, for example waste incineration
      plants. The results of cluster analysis applying different modes of distance
      measure and linkage compared well with neuronal networks. The number of clusters
      was determined based on the stability of the results of different cluster
      analyses and background information.

PMID- 14717165
TI  - Critical evaluation of desorption phenomena of heavy metals from natural
      sediments.
AB  - In natural sediments, the majority of heavy metal ions are generally associated
      with the solid phase. To become bioavailable, the metal ions must desorb from the
      solid. Numerous studies of heavy metals in sediments have suggested that sorption
      and desorption exhibit hysteresis (i.e., the two processes are not reversible),
      while other studies have suggested that desorption hysteresis does not exist. In
      this study, sorption/desorption hysteresis of lead (Pb) and cadmium (Cd) was
      evaluated over the following range of conditions: (i) desorption induced by
      replacing the supernatant liquid with contaminant-free electrolyte solution; (ii)
      desorption induced by lowering the solution pH with mineral acid; and (iii)
      desorption induced by sequestration with EDTA. Given the importance of dissolved
      organic and inorganic ligands in regulating heavy metal behavior in nature
      sediments, sorption/desorption experiments were conducted on both untreated and
      prewashed sediments. Prewashing treatment increases the sorption potential of Cd
      but not Pb. Desorption hysteresis is observed in both the untreated and the
      prewashed sediments using the replaced supernatant method, and the desorption
      hysteresis appears to increase with aging time. Hysteresis is not observed when
      desorption is initiated by lowering the solution pH. A large fraction of the
      sorbed heavy metal ions can be easily desorbed by EDTA; between 0.04 and 1.2
      mmol/kg Cd and Pb ions are resistant to desorption.

PMID- 14717166
TI  - Mechanisms of dioxin formation from the high-temperature pyrolysis of 2
      bromophenol.
AB  - Brominated hydrocarbons are the most commonly used flame retardants. Materials
      containing brominated hydrocarbons are frequently disposed in municipal and
      hazardous waste incinerators as well as being subjected to thermal reaction in
      accidental fires. This results in the potential for formation of brominated
      dioxins and other hazardous combustion byproducts. In contrast to chlorinated
      hydrocarbons, the reactions of brominated hydrocarbons have been studied only
      minimally. As a model brominated hydrocarbon that may form brominated dioxins, we
      studied the homogeneous, gas-phase pyrolytic thermal degradation of 2-bromophenol
      in a 1-cm i.d., fused-silica flow reactor at a concentration of 90 ppm, with a
      reaction time of 2.0 s, and over a temperature range of 300 to 1000 degrees C.
      Observed products included dibenzo-p-dioxin (DD), 1-monobromodibenzo-p-dioxin (1
      MBDD), 4-monobromodibenzofuran (4-MBDF), dibenzofuran (DF), naphthalene,
      bromonaphthalene, 2,4- and 2,6-dibromophenol, phenol, bromobenzene, and benzene.
      These results are compared and contrasted with previous results reported for 2
      chlorophenol. At temperatures lower than 700 degrees C, formation of 2
      bromophenoxyl radical, which decomposes through CO elimination to form a
      bromocyclopentadienyl radical, forms naphthalene and 2-bromonaphthalene through
      radical recombination/rearrangement reactions. However, unlike the results for 2
      chlorophenol, where naphthalene is the major product, DD becomes the major
      product for the pyrolysis of 2-bromophenol. The formation of DD and 1-MBDD are
      attributed to radical-radical reactions involving 2-bromophenoxyl radical with
      the carbon- (bromine) centered radical and the carbon- (hydrogen) centered
      radical mesomers of 2-bromophenoxyl radical, respectively. The potential product,
      4,6-dibromodibenzofuran (4,6-DBDF) for which the analogous product, 4,6
      dichlorodibenzofuran (4,6 DCDF), was observed in the oxidation of 2-chlorophenol,
      was not detected. This is attributed to the pyrolytic conditions of our
      experiments (e.g., shorter reaction times and higher temperatures) that favor
      reaction intermediates that form DD and 1-MBDD.

PMID- 14717167
TI  - Cake-enhanced concentration polarization: a new fouling mechanism for salt
      rejecting membranes.
AB  - Results from well-controlled colloidal fouling experiments with reverse osmosis
      (RO) and nanofiltration (NF) membranes suggest the existence of a new source of
      flux decline for salt-rejecting membranes-cake-enhanced osmotic pressure. The
      physical mechanisms leading to this enhanced osmotic pressure are a combination
      of hindered back-diffusion of salt ions and altered cross-flow hydrodynamics
      within colloidal deposit layers, which lead to an enhanced salt concentration
      polarization layer. A model that accounts for both hindered diffusion of salt
      ions and altered hydrodynamics within colloidal deposit ("cake") layers is
      presented. The model successfully links permeate flux and salt rejection to cake
      enhanced concentration polarization and provides new insight into the mechanisms
      through which salt-rejecting membranes foul. Experimental data support the model
      calculations and highlight the role of enhanced concentration polarization
      phenomena in the performance (i.e., water flux and salt rejection) of polymeric
      thin-film composite RO/NF membranes in environmental applications.

PMID- 14717168
TI  - The effects of reaction-product formation on the reductive dissolution of MnO2 by
      Fe(II).
AB  - We conducted batch-reactor experiments to measure the reductive dissolution of
      pyrolusite-coated (beta-MnO2) quartz by Fe(II) under conditions representative of
      an acid mine-drainage subsurface plume. The results reveal that reductive
      dissolution rates were initially rapid but declined considerably as Fe(III)(aq),
      a product of the reductive-dissolution reaction, was removed from solution by
      heterogeneous precipitation. The inhibition of reductive-dissolution was
      attributed to blocking of the beta-MnO2 surface sites by the Fe(III)(s)
      precipitate. Calculations of a simple model that accounts for the effects of
      Fe(III)(s) precipitate formation on reductive dissolution rates closely match
      temporal changes in Mn(II), Fe(II), and Fe(II) concentrations measured in 10
      experiments, distinguished on the basis of the initial Fe(II)-to-Mn(IV) mole
      ratio and the initial Fe(III)(aq) concentration. The model-data comparisons
      reveal that the initial reaction rate on a clean beta-MnO2 surface exceeds the
      long-term reaction rate by 3 orders of magnitude, highlighting the importance of
      linking Fe(III) precipitation with the reductive dissolution of beta-MnO2 by
      Fe(II).

PMID- 14717169
TI  - Evaluation of Kd underestimation using solid phase microextraction.
AB  - Many important environmental pollutants are strongly adsorbing hydrophobic
      compounds. Because of their potential to adsorb to dissolved organic matter
      (DOM), their partition coefficient Kd may be underestimated by the conventional
      approach due to incomplete phase separation. In this study, solid-phase
      microextraction (SPME) was compared with liquid-liquid partition (LLP) for
      measuring Kd of bifenthrin and permethrin isomers on sediments. Due to its
      selective detection of the freely dissolved concentration, SPME gave Kd values
      0.6-4.4-fold greater than those obtained by LLP in creek and field sediments and
      3.6-21.7-fold greater in nursery runoff sediments. Underestimation by the
      conventional method was attributed to adsorption to DOM that was not excluded
      from the aqueous phase by centrifugation. The degree of underestimation was
      dependent on the source and amount of DOM and may be generally significant for
      compounds that have DOM adsorption coefficient (KDOM) > 10(4). This study
      provides evidence that the existing Kd values for many hydrophobic pollutants may
      be underestimated, and SPME may be a viable, efficacious tool for evaluating the
      underestimation.

PMID- 14717170
TI  - Influence of calcium carbonate on U(VI) sorption to soils.
AB  - The high stability of calcium uranyl carbonate complexes in the circumneutral pH
      range has a strong impact on U(VI) sorption in calcareous soils. To quantify this
      influence, sorption of U(VI) to soils in the presence of naturally occurring
      calcium carbonate was investigated by conducting batch experiments in which
      either U(VI) concentration or solution pH was varied. Two soils containing
      different calcium carbonate concentrations were selected, one from Oak Ridge, TN,
      and another from Altamont Pass, CA. The results show that the presence of calcium
      carbonate in soils strongly affects U(VI) sorption. Higher concentrations of soil
      calcium carbonate lead to a pronounced suppression of the pH-dependent sorption
      curve in the neutral pH range because of the formation of a very stable neutral
      complex of calcium uranyl carbonate in solution. A surface complexation model
      considering both strong and weak sites for ferrihydrite and ionizable hydroxyl
      sites for clay minerals was compared with experimental results, and U(VI) binding
      parameters were reasonably estimated. Fair agreement was found between the model
      predictions and sorption data, which span a wide range of U(VI) concentrations
      and pH. The results also show that appropriate solution-to-solid ratios need to
      be used when measuring distribution coefficients in calcareous soils to avoid
      complete CaCO3 dissolution and consequent dilution of calcium uranyl carbonate
      complexes.

PMID- 14717171
TI  - Voltammetry assisted by multivariate analysis as a tool for speciation of
      metallothioneins: competitive complexation of alpha- and beta-metallothionein
      domains with cadmium and zinc.
AB  - Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) is applied
      to voltammetric data obtained in the study of competitive complexation of Zn(II)
      and Cd(II) by alpha- and beta-domains of metallothionein (MT). The application of
      MCR-ALS allows the estimation of both the voltammograms and the concentration
      profiles associated with each electrochemical process. The complexity of the
      voltammograms obtained in titrations of the alpha- or beta-domains of MT with
      Cd(II) and later Zn(II) (or vice versa) prevents their direct interpretation
      using traditional electrochemical methods. But when MCR-ALS is applied,
      voltammograms can be interpreted rather satisfactorily in both qualitative and
      quantitative terms. MCR-ALS showed the formation of Cd2Znbeta dom and Cd3Znalpha
      dom complexes when both metals were competitively added. A method based on the
      combined use of voltammetry and some chemometric techniques is proposed. It can
      be useful for the metal speciation of environmentally relevant natural ligands.

PMID- 14717172
TI  - Pore-scale analysis of anaerobic halorespiring bacterial growth along the
      transverse mixing zone of an etched silicon pore network.
AB  - The anaerobic halorespiring microorganism, Sulfurospirillum multivorans, was
      observed in the pore structure of an etched silicon wafer to determine how flow
      hydrodynamics and mass transfer limitations along a transverse mixing zone affect
      biomass growth. Tetrachloroethene (PCE, an electron acceptor, 0.2 mM) and lactate
      (an electron donor, 2 mM) were introduced as two separate and parallel streams
      that mixed along a reaction line in the pore structure. The first visible biomass
      occupied a single line of pores in the direction of flow, a few pore bodies from
      the micromodel centerline. This growth was initially present as small aggregates;
      over time, these grew and fused to form finger-like structures with one end
      attached to downgradient ends of the silicon posts and the other end extending
      into pore bodies in the direction of flow. Biomass did not grow in pore throats
      as expected, presumably because shear forces were not favorable. Over the next
      few weeks, the line of growth migrated upward into the PCE zone and extended over
      a width of up to five pore spaces. When the PCE concentration was increased to
      0.5 mM, the microbial biomass increased and growth migrated down toward the
      lactate side of the micromodel. A new analytical model was developed and used to
      demonstrate that transverse hydrodynamic dispersion likely caused the biomass to
      move in the direction observed when the PCE concentration was changed. The model
      was unable, however, to explain why growth migrated upward when the PCE
      concentration was initially constant. We postulate that this occurred because
      PCE, not lactate, sorbed to biofilm components and that biomass on the lactate
      side of the micromodel was limited in PCE. A fluorescent tracer experiment showed
      that biomass growth changed the water flow paths, creating a higher velocity zone
      in the PCE half of the micromodel. These results contribute to our understanding
      of biofilm growth and will help in the development of new models to describe this
      complex process.

PMID- 14717173
TI  - Ion budgets and sediment-water interactions during the experimental acidification
      and recovery of Little Rock Lake, Wisconsin.
AB  - Ion budgets for the two basins of experimentally acidified Little Rock Lake
      (Vilas County, WI, U.S.A.) indicate that Ca2+, Mg2+, and K+ were released from
      the bottom sediments to the water column during 1984-1994, and NH4+, NO3-, and
      SO4(2-) were removed for a net internal alkalinity generation (IAG). Sulfate
      removal contributed approximately 50% of the IAG in the reference basin, and
      cation production generated approximately 40%. In-lake processes in the reference
      basin removed approximately 38% of the sulfate input; 58% was lost to outflow,
      and 4% remained in the water column. As a result of acid additions that
      stimulated sulfate reduction and lower pH that enhanced ion exchange, sulfate
      removal and Ca2+ production were more important for IAG in the treatment basin.
      During 1984-1994, sulfate removal contributed about 61% of the IAG, and Ca2+
      production contributed about half of the IAG from cation production. In the
      treatment basin, in-lake processes removed about 46% of the total input of
      sulfate (including acid additions); 36% was lost to outflow and 18% remained in
      the water column (representing approximately 25% of the added acid). In both
      basins of LRL, NH4+ consumption roughly balanced NO3- consumption, and net N
      transformations provided only 3-12% of the IAG. Overall, Na+ and Cl- were
      conservative in both basins during 1984-1994. Most ion budget components,
      including calculated internal reaction terms, showed fairly large interannual
      variations; e.g., ion inputs (dominated by atmospheric deposition) varied by a
      factor of about two. Over the 10-year period, ANC terms calculated from the
      budgets as the difference between base cation and acid anion terms agreed well
      with measured ANC terms for the budget components, indicating that the budgets
      accounted for all important IAG constituents.

PMID- 14717174
TI  - Behavior of the polycyclic musks HHCB and AHTN in lakes, two potential
      anthropogenic markers for domestic wastewater in surface waters.
AB  - The synthetic polycyclic musks HHCB and AHTN are potential chemical markers for
      domestic wastewater contamination of surface waters. Understanding their
      environmental behavior is important to evaluate their suitability as markers.
      This study focuses on the quantification of the processes that lead to an
      elimination in lakes. Rate constants for all relevant processes were estimated
      based on laboratory studies and models previously described. In lake Zurich,
      during winter time, both compounds are eliminated primarily by outflowing water
      and due to losses to the atmosphere. In summer, direct photolysis represents the
      predominant elimination process for AHTN in the epilimnion of lake Zurich
      (quantum yield, 0.12), whereas for HHCB, photochemical degradation is still
      negligible. HHCB and AHTN were then measured in effluents of Swiss wastewater
      treatment plants (WWTPs), in remote and anthropogenically influenced Swiss
      surface waters, and in Mediterranean seawater using an analytical procedure based
      on SPE and GC-MS-SIM with D6-HHCB as internal standard (LODs for natural waters,
      2 and 1 ng/L, respectively). In winter, concentrations of HHCB and AHTN in lakes
      (<2-47 and <1-18 ng/L, respectively) correlated with the anthropogenic burden by
      domestic wastewater (ratio population per water throughflow), demonstrating the
      suitability of these compounds as quantitative, source-specific markers. In
      summer, however, no such correlations were observed. Vertical concentration
      profiles in lake Zurich indicated significant losses in the epilimnion during
      summer, mainly for AHTN, and could be rationalized with a lake modeling program
      (MASASlight), considering measured, average loads from WWTP effluents (0.80 +/-
      0.22 and 0.32 +/- 0.11 mg person(-1) d(-1) for HHCB and AHTN, respectively) and
      the estimated rate constants for elimination processes.

PMID- 14717175
TI  - Photochemical alkylation of inorganic selenium in the presence of low molecular
      weight organic acids.
AB  - Using a flow-through photochemical reactor and a low pressure mercury lamp as a
      UV source, alkyl selenium species are formed from inorganic selenium(IV) in the
      presence of low molecular weight organic acids (LMW acids). The volatile alkyl Se
      species were cryogenically trapped and identified by GC-MS and GC-ICP-MS. In the
      presence of formic, acetic, propionic and malonic acids, inorganic selenium(IV)
      is converted by UV irradiation to volatile selenium hydride and carbonyl,
      dimethylselenide and diethylselenide, respectively. Se(IV) was successfully
      removed from contaminated agricultural drainage waters (California, U.S.A.) using
      a batch photoreactor system Se. Photochemical alkylation may thus offer a
      promising means of converting toxic selenium salts, present in contaminated
      water, to less toxic dimethylselenide. The LMW acids and photochemical alkylation
      process may also be key to understanding the source of atmospheric selenium and
      are likely involved in its mobility in the natural anaerobic environment.

PMID- 14717176
TI  - Reductive dechlorination of polychlorinated biphenyls: threshold concentration
      and dechlorination kinetics of individual congeners in Aroclor 1248.
AB  - Reductive dechlorination of individual PCB congeners in Aroclor 1248 was
      investigated using sediment microorganisms from the St. Lawrence River (NY). No
      dechlorination was observed at Aroclor concentrations below 40 ppm [137 nmol (g
      of sediment)(-1)]. Above this threshold, congeners could be divided into three
      categories: group A, congeners that dechlorinated above 40 ppm; group B,
      congeners that dechlorinated only at high concentrations above 60 ppm [206 nmol
      (g of sediment)(-1)]; and group C, lower chlorinated congeners that increased in
      concentration. The dechlorination rate of congeners in groups A and B was a
      linear function of their initial sediment concentration. For group A congeners,
      the concentration intercepts of this linear function were the same as their
      concentrations in the Aroclor at the threshold concentration, and these therefore
      represented the threshold values. However, the intercepts of group B congeners
      were significantly higher than their levels at the threshold Aroclor
      concentration and were equivalent to their concentrations in Aroclor 1248 at
      about 75 ppm [258 nmol (g of sediment)(-1)]. The final concentrations of group A
      and group B congeners at the end of dechlorination were the same, regardless of
      their initial concentrations. These final concentrations were significantly lower
      than their threshold values. The accumulation rate of group C congeners was a
      linear function of their initial concentrations, and the total accumulation was
      greater at higher Aroclor concentrations in sediments.

PMID- 14717177
TI  - Classifying NOM-organic sorbate interactions using compound transfer from an
      inert solvent to the hydrated sorbent.
AB  - Interactions of a wide set of organic compounds with model natural organic matter
      (NOM, Pahokee peat) were examined using a new approach that converts aqueous
      sorption to compound transfer from n-hexadecane to the hydrated NOM. This
      conversion accounts for solute-water interactions and applies the same inert
      reference medium for all compounds of interest, making it possible to classify
      sorbates according to the strength of sorbate-NOM interactions. Differences in
      strength of organic compound interactions in the sorbed phase as great as 4-5
      orders of magnitude are demonstrated. The strongest interactions were observed
      for compounds with well-established H-bonding potentials. Considering
      hydrocarbons and Cl-substituted hydrocarbons, aliphatic compounds gain more upon
      distribution from the n-hexadecane medium to NOM than do aromatic compounds.
      Sorption nonlinearity was tested by comparing the change in n-hexadecane-hydrated
      NOM distribution coefficient (K(d,i)) versus sorbed concentration for the
      different compounds. Only those compounds that interact most strongly with NOM
      demonstrated significant sorption nonlinearity, expressed by a strong reduction
      in K(d,i) as a function of sorbed concentration. The relationship between
      compound ability to interact with NOM and reduction in K(d,i) as a function of
      sorbed concentration can be used to characterize compound distribution among
      different sorption domains.

PMID- 14717178
TI  - Products of aqueous chlorination of 17beta-estradiol and their estrogenic
      activities.
AB  - To assess the estrogenic activity potentially stemming from 17beta-estradiol (E2)
      in drinking water, ESI-LC-MS was used to identifythe products of its aqueous
      chlorination under the following conditions: 50 microg/L E2, 1.46 mg/L sodium
      hypochlorite, pH 7.5, 25 degrees C. Seven products, including 2,4-dichloro-17beta
      estradiol, monochloroestrone, 2,4-dichloroestrone, and the four byproducts such
      as 4-[2-(2,6-dichloro-3-hydroxyphenyl)ethyl]-7alpha-methyloctahydroinden-5-one
      (product C in the text) were identified in chlorinated E2 solution. The
      estrogenic activities of the aqueous chlorinated E2 solution at 10, 30, 60, 120,
      and 180 min contact time were assessed by a yeast two-hybrid system based on the
      ligand-dependent interaction of two proteins, a human estrogen receptor (ER) and
      a coactivator. All five solutions elicited transcriptional activation induction.
      The maximal beta-galactosidase activities induced by the chlorinated solution at
      10, 30, and 60 min were similar and slightly lower than those before
      chlorination, while the activities of the chlorinated solution at 120 and 180 min
      were about 40% of those before chlorination. Finally, 4-chloro-17beta-estradiol
      (4-chloro-E2) (we failed to synthesize the 2-chloroestrone (2-chloro-E1)), 2,4
      dichloro-17beta-estradiol (2,4-dichloro-E2), and 2,4-dichloroestrone (2,4
      dichloro-E1) were synthesized, and product C was fractionated by HPLC. It was
      found that 4-chloro-E2 elicited strong estrogenic activity, at almost the same
      level as that of estrone (EC50 = 10(2) nM), while 2,4-dichloro-E2 elicited weaker
      beta-galactosidase activity compared with that of 4-chloro-E2. The EC50 was ca.
      10(3) nM. The maximal beta-galactosidase activity for 2,4-dichloro-E1 was lower
      than that of 2,4-dichloro-E2, while its EC50 was similar to that of 2,4-dichloro
      E2. In addition, product C, 4-[2-(2,6-dichloro-3-hydroxyphenyl)ethyl]-7alpha
      methyloctahydroinden-5-one, induced high beta-galactosidase activity at the
      relatively higher concentration of 3.5 x 10(5) nM. On the basis of the dose
      response curve of a single byproduct of chlorinated E2, the estrogenic activity
      at 120 and 180 min appears to be induced mainly by 2,4-dichloro-E2 and 2,4
      dichloro-E1.

PMID- 14717179
TI  - Surface chemical heterogeneity of bacteriogenic iron oxides from a subterranean
      environment.
AB  - This study quantifies the surface chemical heterogeneity of bacteriogenic iron
      oxides (BIOS) and its end-members (2-line ferrihydrite and intermixed intact and
      fragmented bacteria). On a dry weight basis, BIOS consisted of 64.5 +/- 1.8%
      ferrihydrite and 34.5 +/- 1.8% organic matter. Enrichment of Al, Cu, Cr, Mn, Sr,
      and Zn was shown in the solid versus the aqueous phase (1.9 < log Kd < 4.2).
      Within the solid-phase Al (69.5%), Cu (78.7%), and Zn (77.9%) were associated
      with the bacteria, whereas Cr (59.8%), Mn (99.8%), and Sr (79.4%) preferred
      ferrihydrite. Acid-base titration data from the BIOS and bacteria were fitted
      using FOCUS pKa spectroscopy. The bacteria spectrum with pKa's of 4.18 +/- 0.37,
      4.80 +/- 0.54, 6.98 +/- 0.45, and 9.75 +/- 0.68 was similar to discrete and
      continuous spectra for intact and fragmented bacteria. The BIOS spectrum recorded
      pKa's of 4.27 +/- 0.51, 6.61 +/- 0.51, 7.89 +/- 1.10, and 9.65 +/- 0.66 and was
      deconvoluted to remove overlapping binding site contributions from the bacteria.
      The resulting residual iron oxide spectrum coincided with discrete MUSIC spectra
      for goethite and lepidocrocite with pKa values of 4.10 +/- 0.43, 6.53 +/- 0.45,
      7.81 +/- 0.76, and 9.51 +/- 0.68. Surface site density analysis showed that
      acidic sites (pKa < 6) were contributed by the bacteria (37%), whereas neutral
      sites (6 < pKa < 8) were characteristic of the iron oxide fraction (35%). Basic
      sites (8 < pKa) were higher in the bacteria (57%), than in the BIOS (44%) or iron
      oxide fractions (47%). This analysis suggested a high degree of bacterial group
      masking and a similarity between the BIOS and goethite surface reactivity. An
      understanding of the BIOS surface chemical heterogeneity and inherent proton and
      metal binding capacity was obtained through the use of FOCUS apparent pKa
      spectroscopy.

PMID- 14717180
TI  - Congener-based Aroclor quantification and speciation techniques: a comparison of
      the strengths, weaknesses, and proper use of two alternative approaches.
AB  - This paper compares two previously published methods, an Aroclor estimation
      method and a mixing model method, that relate Aroclor contamination to congener
      specific data in environmental samples. The Aroclor estimation method, which is
      consistent with U.S. EPA Method 8082, uses a limited set of congener specific
      data to estimate Aroclor contributions to the sample, while the mixing model
      method uses the full congener data to model sample compositions as linear
      combinations of Aroclors. The performance of these methods are compared, using
      181 samples at a variety of trophic levels, in terms of (a) total PCB
      concentrations, (b) compositional modification levels from original Aroclors, and
      (c) determination of the Aroclor mixture or mixtures best describing the sample
      (Aroclor speciation). We find that the two methods agree in all three terms for
      samples of low trophic level, but disagree for samples of higher tropic levels.
      Most significantly, the comparison reveals systematic overestimation of total PCB
      content by the Aroclor estimation method for samples at high trophic levels. The
      implication is that Aroclor determinations using persistent congeners cannot
      reliably be used as surrogates for total PCB concentration. The strengths and
      weaknesses of each method are detailed.

PMID- 14717181
TI  - Disposable indicators for monitoring lighting conditions in museums.
AB  - Photoinduced alterations of light-sensitive artifacts represent one of the main
      problems that conservators and curators have to face for environmental control in
      museums and galleries. Therefore, increasing attention has been recently devoted
      to developing strategies of indoor light monitoring, especially aimed at
      minimizing the cumulated light exposure for the objects on exhibit. In this work
      a prototype of a light dosimeter, constituted by a photosensitive dyes/polymer
      mixture applied on a paper substrate, is presented. This indicator, specially
      designed for a preventive assessment of the risk of damage for highly light
      sensitive objects, undergoes a progressive color variation as its exposure to the
      light increases. Different, easily distinguishable color steps are exhibited
      depending on the light dose received, so that the dosimeter can be used
      straightforwardly to have a first, instrumentation-free estimation of the total
      light exposure. A reflectance spectroscopy study in the 350-860 nm range was
      carried out on prototype dosimeters exposed to light emitted from a tungsten
      halogen lamp to investigate the response of the dosimeter to the light and to
      study the fading mechanism. Two different approaches were evaluated for the
      calibration of the prototype: colorimetry and principal component analysis of the
      reflectance spectra. The usefulness of the two methods in providing a
      quantitative indication of the light dose received was evaluated.

PMID- 14717182
TI  - Portable sick house syndrome gas monitoring system based on novel colorimetric
      reagents for the highly selective and sensitive detection of formaldehyde.
AB  - Formaldehyde (HCHO) emitted from the furniture and the walls in the rooms injures
      the eyes, nose, and respiratory organs and causes allergies, which is called sick
      house syndrome. We designed and synthesized novel colorimetric HCHO-sensing
      molecules (KD-XA01 and KD-XA02) which possess an enaminone structure and
      developed a hand-held instrument to monitor indoor HCHO gas with the use of KD
      XA01. These sensing molecules produced speedy color changes from colorless to
      yellow under mild conditions, which was caused by the fact that the enaminone
      structure in the reagent reacts with HCHO to give a lutidine derivative. This
      reaction took place not only in the solution phase but also in the solid phase
      (surface of the cellulose paper). To take advantage of this phenomena, a handy
      and rapid monitoring system has been developed for detecting indoor HCHO gas
      using a highly sensitive and selective detection tablet constructed from the
      porous cellulose paper that contains silica gel as an adsorbent, KD-XA01, and
      phosphoric acid under optimum conditions. This instrument detected the surface
      color change of the tablet from white to yellow, which was monitored as a
      function of the intensity of the reflected light illuminated by an LED (475 nm).
      The response was proportional to the HCHO concentration at a constant sampling
      time and flow rate; 0.05 ppm HCHO, which is under the standard value set by the
      World Health Organization, was able to be detected in 5 min. The detection limit
      was 0.005 ppm. This monitoring system was not interfered by carbonyl compounds
      such as acetaldehyde and acetone, alcohols, hydrocarbons, and typical gases such
      as carbon monoxide, carbon dioxide, nitrogen dioxide, etc., which contributes to
      the measurement of correct HCHO concentrations. It was possible to monitor the
      HCHO gas in the room of a new apartment and school using this instrument; the
      response values were in good agreement with those obtained by the standard DNPH
      method. This highly sensitive, selective, and handy HCHO gas monitor is widely
      applicable and convenient for users who are not specialists in this field.

PMID- 14717183
TI  - Fluorescence excitation-emission matrix regional integration to quantify spectra
      for dissolved organic matter.
AB  - Excitation-emission matrix (EEM) fluorescence spectroscopy has been widely used
      to characterize dissolved organic matter (DOM) in water and soil. However,
      interpreting the > 10,000 wavelength-dependent fluorescence intensity data points
      represented in EEMs has posed a significant challenge. Fluorescence regional
      integration, a quantitative technique that integrates the volume beneath an EEM,
      was developed to analyze EEMs. EEMs were delineated into five excitation-emission
      regions based on fluorescence of model compounds, DOM fractions, and marine
      waters or freshwaters. Volumetric integration under the EEM within each region,
      normalized to the projected excitation-emission area within that region and
      dissolved organic carbon concentration, resulted in a normalized region-specific
      EEM volume (phi(i,n)). Solid-state carbon nuclear magnetic resonance (13C NMR),
      Fourier transform infrared (FTIR) analysis, ultraviolet-visible absorption
      spectra, and EEMs were obtained for standard Suwannee River fulvic acid and 15
      hydrophobic or hydrophilic acid, neutral, and base DOM fractions plus
      nonfractionated DOM from wastewater effluents and rivers in the southwestern
      United States. DOM fractions fluoresced in one or more EEM regions. The highest
      cumulative EEM volume (phi(T,n) = sigma phi(i,n)) was observed for hydrophobic
      neutral DOM fractions, followed by lower phi(T,n) values for hydrophobic acid,
      base, and hydrophilic acid DOM fractions, respectively. An extracted wastewater
      biomass DOM sample contained aromatic protein- and humic-like material and was
      characteristic of bacterial-soluble microbial products. Aromatic carbon and the
      presence of specific aromatic compounds (as indicated by solid-state 13C NMR and
      FTIR data) resulted in EEMs that aided in differentiating wastewater effluent DOM
      from drinking water DOM.

PMID- 14717184
TI  - A continuous analyzer for soluble anionic constituents and ammonium in
      atmospheric particulate matter.
AB  - A new continuous soluble particle collector (PC) that does not use steam is
      described. Preceded by a denuder and interfaced with an ion chromatograph, this
      compact collector (3 in. o.d., approximately 5 in. total height) permits
      collection and continuous extraction of soluble components in atmospheric
      particulate matter. The PC is mounted atop a parallel plate wetted denuder for
      removal of soluble gases. The soluble gas denuded air enters the PC through an
      inlet. One version of the PC contained an integral cyclone-like inlet. For this
      device, penetration of particles as a function of size was characterized. In the
      simpler design, the sampled air enters the PC through a nozzle, and deionized
      water flows through a capillary tube placed close to the exit side of the nozzle
      by Venturi action or is forcibly pumped. Some growth of the aerosol occurs in the
      highly humid mist-chamber environment, but the dominant aerosol capture mechanism
      involves capture by the water film that forms on the hydrophobic PTFE membrane
      filter that constitutes the top of the PC and the airflow exit. Water drops
      coalesce on the filter and fall below into a purpose-machined cavity equipped
      with a liquid sensor. The water and the dissolved constituents are aspirated by a
      pump onto serial cation and anion preconcentrator columns. NH4+ captured by the
      cation preconcentrator is eluted with NaOH and is passed across an asymmetric
      membrane device. NH3 diffuses from the alkaline donor stream into a deionized
      water flowing countercurrent; the conductivity of the latter provides a measure
      of ammonium. The anions on the anion preconcentrator column are eluted and
      measured by a fully automated ion chromatography system. The total system thus
      provides automated semicontinuous measurement of soluble anions and ammonium.
      With a 15 min analytical cycle and a sampling rate of 5 L/min, the limit of
      detection (LOD) for ammonium is 8 ng/m3 and those for sulfate, nitrate, and
      oxalate are < or = 0.1 ng/m3. The system has been extensively field tested.

PMID- 14717185
TI  - Direct injection GC method for measuring light hydrocarbon emissions from cooling
      tower water.
AB  - A Direct Injection GC method for quantifying low levels of light hydrocarbons (C6
      and below) in cooling water has been developed. It is intended to overcome the
      limitations of the currently available technology. The principle of this method
      is to use a stripper column in a GC to strip waterfrom the hydrocarbons prior to
      entering the separation column. No sample preparation is required since the water
      sample is introduced directly into the GC. Method validation indicates that the
      Direct Injection GC method offers approximately 15 min analysis time with
      excellent precision and recovery. The calibration studies with ethylene and
      propylene show that both liquid and gas standards are suitable for routine
      calibration and calibration verification. The sampling method using zero
      headspace traditional VOA (Volatile Organic Analysis) vials and a sample chiller
      has also been validated. It is apparent that the sampling method is sufficient to
      minimize the potential for losses of light hydrocarbons, and samples can be held
      at 4 degrees C for up to 7 days with more than 93% recovery. The Direct Injection
      GC method also offers <1 ppb (w/v) level method detection limits for ethylene,
      propylene, and benzene. It is superior to the existing El Paso stripper method.
      In addition to lower detection limits for ethylene and propylene, the Direct
      Injection GC method quantifies individual light hydrocarbons in cooling water,
      provides better recoveries, and requires less maintenance and setup costs. Since
      the instrumentation and supplies are readily available, this technique could
      easily be established as a standard or alternative method for routine emission
      monitoring and leak detection of light hydrocarbons in cooling-tower water.

PMID- 14717186
TI  - Determination of strongly reducing substances in sediment.
AB  - Reducing substances in sediments play an important role in regulating the
      chemical and biological status of the sediment. Strongly reducing substances are
      the most active part of them, and are difficult to measure directly. In this
      work, we have developed a method for their determination based on the oxidation
      by Fe(III). Then, the produced Fe(II) was determined by colorimetry, using 2,2'
      bipyridine as the chelating agent. Prior to determination, these substances were
      extracted from the sediment by M acetic acid. The whole process was carried out
      in a closed system, so that oxidation of Fe(II) and reducing substances by
      atmospheric oxygen could be avoided. The calibration curve between absorbance and
      Fe(II)-chelate concentration in extract was linear. When ascorbic acid was added
      to the extract, the recovery was larger than 94.0%. The effect of surplus Fe(III)
      on the result was discussed. With the proposed method, the concentration of
      strongly reducing substances in sediment samples from Dianchi Lake of China was
      measured with good reproducibility.

PMID- 14717187
TI  - Prototype for in situ detection of atmospheric NO3 and N2O5 via laser-induced
      fluorescence.
AB  - We describe a prototype designed for in situ detection of the nitrate radical
      (NO3) by laser-induced fluorescence (LIF) and of N2O5 by thermal dissociation
      followed by LIF detection of NO3. An inexpensive 36 mW continuous wave multi-mode
      diode laser at 662 nm is used to excite NO3 in the B2E'(0000) <-- X2A'2(0000)
      band. Fluorescence is collected from 700 to 750 nm. The prototype has a
      sensitivity to NO3 of 76 ppt for a 60 s integration with an accuracy of 8%.
      Although this sensitivity is adequate for studies of N205 in many environments,
      it is much less sensitive (about 300 times) than expected based on a comparison
      of previously measured photophysical properties of NO2 and NO3. This implies much
      stronger nonradiative coupling of electronic states in NO3 than in NO2.

PMID- 14717188
TI  - Quantification of metallothionein-like proteins in the mussel Mytilus
      galloprovincialis using RP-HPLC fluorescence detection.
AB  - A HPLC-fluorescence method, using the fluorophore SBD-F (ammonium-7-fluorobenz-2
      oxa-1,3-diazole-4-sulfonate), was adapted for the quantification of
      metallothioneins and their isoforms from the Moroccan mussel Mytilus
      galloprovincialis. The method was first optimized using a rabbit liver
      metallothionein. The effects of EDTA, tris(2-carboxyethyl)phosphine, and SBD-F on
      the labeling efficiency were studied. The optimized method was then applied to
      evaluate the amount of metallothionein in the mussels either exposed to cadmium
      in the laboratory or collected from the Casablanca coast, Morocco. The
      concentrations of metallothioneins measured in the field samples describe the
      degree of contamination of the sites and are reflected by distinct isoform
      patterns.

PMID- 14717189
TI  - Mechanism and kinetics of the catalytic oxidation of aqueous ammonia to molecular
      nitrogen.
AB  - Aqueous phase catalytic oxidation of ammonia has been studied over Ru/TiO2
      catalyst in a batch reactor by changing the solution pH, concentration of
      catalyst in the solution, temperature, and reaction time. The oxidation reaction
      of ammonia over Ru/TiO2 catalyst has been found to take place exclusively for the
      aqueous NH3 with a preferred mode in strong alkaline pH region. An oxidation
      reaction pathway has been proposed as follows: Oxidation of ammonia is initiated
      by the reaction of aqueous ammonia with catalytically activated oxygen. After
      undergoing further successive oxidation reactions with activated oxygen, ammonia
      is finally oxidized to a molecule of nitrous acid. Nitrous acid dissociates into
      a nitrite ion and a proton. The solution pH is decreased with the protons from
      the dissociation of HNO2 so that the solution concentration of NH4+ is increased.
      Molecular nitrogen as a final product is produced from the homogeneous aqueous
      phase reaction between nitrous ion and ammonium ion. Further reaction of nitrous
      ion with the activated oxygen leads to the formation of nitrate ion. The reaction
      pathway proposed has been validated with the changes of solution pH along with
      the ammonia conversions, and the formation of N2 from the solution containing NO2
      and NH4+ ions in equimolar amounts of nitrogen has been confirmed in a separate
      experiment. The kinetics of aqueous ammonia oxidation reaction has been well
      represented as a first-order reaction with respect to the concentration of
      aqueous ammonia, and an apparent rate constant has been obtained as a function of
      catalyst concentration in solution, oxygen pressure, and reaction temperature.

PMID- 14717190
TI  - Arsenic(III) oxidation by iron(VI) (ferrate) and subsequent removal of arsenic(V)
      by iron(III) coagulation.
AB  - We investigated the stoichiometry, kinetics, and mechanism of arsenite [As(III)]
      oxidation by ferrate [Fe(VI)] and performed arsenic removal tests using Fe(VI) as
      both an oxidant and a coagulant. As(III) was oxidized to As(V) (arsenate) by
      Fe(VI), with a stoichiometry of 3:2 [As(III):Fe(VI)]. Kinetic studies showed that
      the reaction of As(III) with Fe(VI) was first-order with respect to both
      reactants, and its observed second-order rate constant at 25 degrees C decreased
      nonlinearly from (3.54 +/- 0.24) x 10(5) to (1.23 +/- 0.01) x 10(3) M(-1) s(-1)
      with an increase of pH from 8.4 to 12.9. A reaction mechanism by oxygen transfer
      has been proposed for the oxidation of As(III) by Fe(VI). Arsenic removal tests
      with river water showed that, with minimum 2.0 mg L(-1) Fe(VI), the arsenic
      concentration can be lowered from an initial 517 to below 50 microg L(-1), which
      is the regulation level for As in Bangladesh. From this result, Fe(VI) was
      demonstrated to be very effective in the removal of arsenic species from water at
      a relatively low dose level (2.0 mg L(-1)). In addition, the combined use of a
      small amount of Fe(VI) (below 0.5 mg L(-1)) and Fe(III) as a major coagulant was
      found to be a practical and effective method for arsenic removal.

PMID- 14717191
TI  - Subcritical (hot/liquid) water dechlorination of PCBs (Aroclor 1254) with metal
      additives and in waste paint.
AB  - No disposal option exists for "mixed wastes" such as paint scrapings that are co
      contaminated with polychlorinated biphenyls (PCBs) and radioactive metals. Either
      removal or destruction of the PCBs is required prior to disposal. Comparison of
      subcritical water dechlorination (350 degrees C, 1 h) of Aroclor 1254 in paint
      scrapings (180 ppm) and of standard Aroclor 1254 showed significantly enhanced
      dechlorination in the presence of paint. While no significant degradation was
      observed for standard Aroclor (no paint), the dechlorination of PCBs in paint was
      99, 99, and 80% for the hepta-, hexa-, and pentachlorinated congeners,
      respectively, indicating that metals in the paint enhanced the dechlorination
      reactions. Adding metals to the standard Aroclor (no paint) reactions enhanced
      PCB dechlorination in subcritical water in descending order of activity: Pb
      approximately = Cu > Al > Zn > Fe. In the presence of both zerovalent and
      divalent lead and zerovalent copper in subcritical water (350 degrees C, 1 h),
      99% of the Aroclor 1254 mixture (tetra- to heptachlorinated biphenyls) was
      dechlorinated. High dechlorination (ca. 95%) was also achieved with zerovalent
      aluminum. In contrast to other metals, lead retained its degradation ability at a
      lower temperature of 250 degrees C after 18 h. The high degradation efficiency
      achieved using metal additives in water at reasonable temperatures and pressures
      demonstrates the potential for subcritical water dechlorination of PCBs in paint
      scrapings and, potentially, in other solid and liquid wastes.

PMID- 14717192
TI  - Simulation and evaluation of elemental mercury concentration increase in flue gas
      across a wet scrubber.
AB  - Experimental data from a laboratory-scale wet scrubber simulator confirmed that
      oxidized mercury, Hg2+, can be reduced by aqueous S(IV) (sulfite and/or
      bisulfite) species and results in elemental mercury (HgO) emissions under typical
      wet FGD scrubber conditions. The S(IV)-induced Hg2+ reduction and Hg0 emission
      mechanism can be described by a model which assumes that only a fraction of the
      Hg2+ can be reduced, and the rate-controlling step of the overall process is a
      first-order reaction involving the Hg-S(IV) complexes. Experimental data and
      model simulations predict that the Hg2+ in the flue gas can cause rapid increase
      of Hg0 concentration in the flue gas across a FGD scrubber. Forced oxidation can
      enhance Hg2+ reduction and Hg0 emission by decreasing the S(IV) concentration in
      the scrubbing liquor. The model predictions also indicate that flue gas Hg0
      increase across a wet FGD scrubber can be reduced by decreasing the pH,
      increasing S(IV) concentration, and lowering the temperature.

PMID- 14717193
TI  - Mechanisms of the aqueous photodegradation of polycyclic aromatic hydrocarbons.
AB  - The role of O2 and photoionization as well as the involvement of polycyclic
      aromatic hydrocarbon (PAH) cation radicals (P+) in the photodegradation of nine
      PAHs was examined. Photodegradation quantum yields for all PAHs increased with
      increasing O2 concentration, illustrating the key role of O2 in the
      photodegradation mechanism. In the presence of a series of electron donors (to
      P+), the photodegradation rate constants of most PAHs were largely unaffected at
      low O2 concentrations (< or = 250 microM), indicating that P+ is not extensively
      produced. However, at higher O2 concentrations (up to 1.2 mM), the presence of
      the donors substantially lowered photodegradation rates for most PAHs, indicating
      that P+ is produced and is arising from O2 reaction with the excited singlet
      state. Because little P+ was detected at low O2 concentrations and, further,
      because degradation rates were not enhanced in the presence of N2O, we conclude
      that photoionization is unimportant. With some exceptions, photodegradation can
      proceed through reaction of O2 with both excited singlet and triplet states of
      the PAHs. Our results indicate that photodegradation via the excited singlet
      state occurs primarily through electron transfer to O2, whereas degradation via
      the triplet occurs predominately through a direct reaction of O2 with the PAH
      within the collision complex.

PMID- 14717194
TI  - Dechlorination of polychlorinated biphenyls in industrial transformer oil by
      radiolytic and photolytic methods.
AB  - Used electrical transformer oils containing low or high concentrations of
      polychlorinated biphenyls (PCBs) were treated using electron, gamma, and
      ultraviolet radiation, and the conditions for complete dechlorination were
      developed. Dechlorination was determined by analysis of the inorganic chloride
      formed and the concentrations of remaining PCBs. Transformer oil containing
      approximately 95 microg g(-1) PCB (approximately 3.5 mmol L(-1) Cl) is completely
      dechlorinated by irradiation with 600 kGy after the addition of 10% triethylamine
      (TEA). Transformer oil containing >800,000 microg g(-1) PCB (17.7 mol L(-1) Cl)
      requires an additional solvent to prevent solidification. When this oil is
      diluted with 2-propanol (2-PrOH) and TEA (v/v/v, 1/79/20), complete
      dechlorination is achieved with a dose of 2500 kGy. Ultraviolet photolysis of the
      same oil/2-PrOH/TEA solutions led to 90% dechlorination after exposure for 120 h
      in our experimental setup. Such yields were obtained by radiolysis with a dose of
      2000 kGy (300 h in our Gammacell). Replacing TEA with KOH in 2-PrOH solutions
      greatly increases the yield of dechlorination in both the radiolytic and the
      photolytic experiments, demonstrating that a chain reaction plays a role in both
      of these treatment methods and suggesting that both methods deserve further
      consideration for large-scale application.

PMID- 14717195
TI  - Pyrene degradation in the rhizosphere of tall fescue (Festuca arundinacea) and
      switchgrass (Panicum virgatum L.).
AB  - A growth chamber study was conducted to investigate the fate of pyrene in the
      rhizosphere of tall fescue (Festuca arundinacea) and switchgrass (Panicum
      virgatum L.). For this study, 14C-labeled pyrene was used, and distribution of
      14C activity was assessed after plant establishment. After 190 days of
      incubation, 37.7 and 30.4% of 14C-pyrene was mineralized in the soil planted with
      tall fescue and switchgrass, respectively, while 4.3% mineralization was observed
      for the unplanted control. Only 7.6 and 8.7% of pyrene was recovered from the
      soil in the two planted treatments, while 31.5% of pyrene remained in the
      unplanted control. Significant amounts of 14C were observed for all treatments
      and controls in the humic/fulvic fraction of soil at the end of the experiment.
      This research indicates the potential for pyrene mineralization in planted
      systems, although the ultimate fate of degradation byproducts is uncertain.

PMID- 14717196
TI  - Modeling of thin-film slurry photocatalytic reactors affected by radiation
      scattering.
AB  - Photocatalytic oxidation over titanium dioxide is a "green" sustainable process
      for treatment and purification of water and wastewater. A dimensionless model for
      steady-state, continuous flow, thin-film, slurry (TFS) photocatalytic reactors
      for water purification using solar radiation and UV lamps is presented and
      validated. The model is applicable to TFS flat plate and annular photoreactors of
      (a) falling film or (b) double-skin designs, operating with three ideal flows:
      (1) falling film laminar flow (FFLF), (2) plug flow (PF) and (3) slitflow (SF).
      Model parameters can be estimated easily from real systems, and solutions can be
      obtained with modest computational efforts. A modified two-flux absorption
      scattering model models the radiation field in the photoreactor. Model
      simulations show that at a scattering albedo higher than 0.3, radiation
      scattering can significantly affect conversions obtained at different values of
      optical thickness. However, at lower values, the effect of scattering on
      conversions is negligible. The conversions with the idealized flow systems follow
      the sequence FFLF > PF > SF. SF operation should always be avoided. The model
      estimates the optimum value of optical thickness that maximizes conversion in a
      photocatalytic reactor. Optimal design of TFS photocatalytic reactors using the
      photocatalyst TiO2 Degussa P25 requires an optical thickness in the range from
      1.8 to 3.4 depending on flow conditions and reaction kinetics.

PMID- 14717197
TI  - Sorption of basic dyes onto iron humate.
AB  - Iron humate (IH) was examined as a new low-cost sorbent for removing basic dyes
      (Methylene Blue, Methyl Violet, Crystal Violet, Malachite Green, and Rhodamine B)
      from waters. The sorption of the dyes from aqueous solutions was described by a
      multisite Langmuir isotherm; the sorption capacities ranging from ca. 0.01 to
      0.09 mmol/g were calculated from the parameters of the isotherm for individual
      dyes. A more detailed study was carried out with Methylene Blue to examine an
      influence of the composition of aqueous phase on the sorption. pH and the
      presence of inorganic salts have only minor effects on the sorption. The presence
      of anionic surfactant (sodium dodecyl sulfate, SDS) increases dramatically the
      sorption of Methylene Blue. A model describing the sorption of basic (cationic)
      dyes in the presence of anionic surfactants was proposed; two main mechanisms are
      considered in this model: the sorption of cationic dyes onto the polar (or cation
      exchange) active sites and the sorption of relatively small dye-surfactant
      aggregates onto the nonpolar part of the sorbent. Experimental dependencies
      comply well with those predicted from the model. Both in the presence as well as
      in the absence of SDS, the dye sorption proceeds relatively quickly--most of the
      dye is sorbed within the first several hours. Leachability of the dye from the
      loaded sorbent was found to be very low, especially with water as leachant.

PMID- 14717198
TI  - Aminated polyacrylonitrile fibers for humic acid adsorption: behaviors and
      mechanisms.
AB  - Aminated polyacrylonitrile fibers (APANFs) were prepared by surface modification
      of polyacrylonitrile fibers (PANFs) with diethylenetriamine in a solution, and
      the APANFs were studied as an adsorbent for humic acid removal in a series of
      batch adsorption experiments. The surface modification reaction introduced the
      amine groups on the surface of the fibers, and the APANFs had a zero point of
      zeta potentials at pH 8.1, in contrast with pH 3.5 for the PANFs. Adsorption
      experiments indicated that the APANFs were very effective in removing humic acid
      from aqueous solutions in the pH range of 2-10, whereas the PANFs did not adsorb
      humic acid at all under the same conditions. It was found that both electrostatic
      interaction and surface complexation mechanisms played important roles in humic
      acid adsorption on the APANFs, although the relative importance of each of the
      adsorption mechanisms varied with solution pH values. With the advantages of
      large specific surface areas and enhanced reactive surface properties, the APANFs
      have great potentials in water treatment for the removal of humic substances and
      other polarized or electrically charged species.

PMID- 14717199
TI  - Investigation of the inhibitory effect of silica on the degradation of 1,1,1
      trichloroethane by granular iron.
AB  - Although iron-based permeable reactive barriers are gaining importance for
      treating groundwater contaminants, little is currently known about the effect of
      cosolutes on barrier longevity. Because of their corrosion inhibiting properties,
      dissolved silica species are of particular concern. This research investigates
      the effect of silica on the reduction of 1,1,1-trichloroethane by granular iron
      as a function of added silica concentration, pH, and duration of iron exposure to
      dissolved silica. Batch studies reveal that, at pH 8.5 and above, added silica
      concentrations as low as 0.17 mM cause a 30% reduction in the reactivity of iron.
      At higher silica concentrations, reactivity decreases by 65-75%. The inhibitory
      effect is greater at higher pH: 0.83 mM silica has no apparent adverse effect at
      pH 7.5, but leads to a 46% decrease in reaction rate at pH 8 and 90% at pH 9.
      This corresponds to observed trends in silica adsorption onto iron, which is low
      at pH 7.3 but increases at higher pH. Extending the duration of iron exposure to
      silica solutions also leads to a more pronounced inhibitory effect. This is in
      good agreement with the increase in silica coverage on the iron surface as
      revealed by X-ray photoelectron spectroscopy.

PMID- 14717200
TI  - Environmental remediation by an integrated microwave/UV illumination method. V.
      Thermal and nonthermal effects of microwave radiation on the photocatalyst and on
      the photodegradation of rhodamine-B under UV/Vis radiation.
AB  - The photocatalyzed degradation (PD) of the cationic rhodamine-B (RhB) dye was
      examined in aqueous TiO2 dispersions using UV/Vis illumination assisted by
      microwave radiation (PD/MW). The initial degradation by the PD/MW method is
      compared to the PD method and to the thermally assisted PD method using
      conventional heating (PD/TH). Total organic carbon (TOC) assays show that the
      efficiency of complete mineralization of the dye follows PD/MW > PD/TH > PD > MW.
      In all cases, microwave radiation alone had no effect on the loss of TOC. The
      degradation involving microwave radiation was especially efficient when coupled
      to UV irradiation. By contrast, the extent of degradation of RhB involving
      suitable excited states through visible irradiation of the dye was rather
      inefficient when coupled to microwave radiation. Contact angle measurements on
      the TiO2 photocatalyst particles indicate that microwave radiation also causes an
      increase in the hydrophobic character of the TiO2 surface, with consequences on
      the adsorption mode of the dye substrate and thus on the overall mechanism of
      degradation. Deethylated RhB intermediates were identified by an electrospray ESI
      ionization mass spectral technique in the positive ion mode and subsequently
      confirmed by HPLC/absorption spectroscopy. Computer simulations led to estimates
      of frontier electron densities of all atoms of the RhB structure, affording
      inferences as to the position of radical attack on RhB. The nitrogen atoms of the
      dye were all converted to NH4+ ions. The major difference between the thermally
      assisted PD/TH method and the microwave-assisted PD/MW method showed that
      nonthermal effects from the microwave radiation impact significantly on the
      nature of the photocatalyst surface. These effects led to a more efficient
      photodegradation and mineralization of the dye substrate.

PMID- 14717201
TI  - Trichloroethylene degradation in a coupled anaerobic/aerobic reactor oxygenated
      using hydrogen peroxide.
AB  - In this work, trichloroethylene (TCE) degradation under combined anaerobic
      aerobic conditions was studied in an ethanol-fed biofilm reactor oxygenated using
      hydrogen peroxide. The reactor was inoculated with a biomass originating from an
      anaerobic digestor. Granulated peat was added to the reactor as a substratum for
      biofilm development. Extensive characterization of reactor populations using
      activity tests and PCR analysis revealed the development of a mutualistic
      consortium, particularly methanotrophic and methanogenic microorganisms. This
      consortium was shown to degrade TCE by a combination of reductive and oxidative
      pathways. A near complete degradation of TCE at a load of 18 mg L(R)(-1) day(-1)
      was evidenced by a stoichiometric release of inorganic chloride.

PMID- 14717202
TI  - Pilot-scale demonstration of cyclodextrin as a solubility-enhancement agent for
      remediation of a tetrachloroethene-contaminated aquifer.
AB  - The limitations associated with conventional pump and treat technology have
      generated interest in using enhanced in-situ flushing as an alternative for
      remediating source zones contaminated with immiscible liquid. This research
      investigates the effectiveness of cyclodextrin as a solubility-enhancement agent
      to enhance the removal of tetrachloroethene (PCE) from a physically isolated
      section of an aquifer. An important component of this project was the
      implementation of reagent recovery and reuse. This field experiment presented the
      rare opportunity, under strict regulatory guidance, to inject PCE into the
      surficial aquifer cell created with two sets of sheet piles driven into an
      underlying clay unit. The well-controlled conditions specific to this experiment
      allowed quantification of mass balances, which is problematic for many
      contaminated field sites. The fact that mass balances can be obtained provides
      the ability to determine remediation effectiveness with unusual accuracy for a
      field project. The saturated zone within the test cell was flushed with a 15 wt %
      cyclodextrin solution. The cyclodextrin solution increased the aqueous
      concentration of PCE in the extraction-well effluent to as much as 22 times the
      concentrations obtained during the water flush conducted prior to the complexing
      sugar flush (CSF). The seven pore-volume CSF removed the equivalent of
      approximately 33 L of PCE from the subsurface. This equates to 48% of the total
      initial mass, based on the volume of PCE present prior to the CSF (68.6 L).
      Conversely, the seven pore-volume water flush conducted prior to the CSF removed
      the equivalent of 2.7 L of PCE. The use of cyclodextrin as a flushing agent,
      especially in a recycling configuration, appears to hold promise for successful
      remediation of chlorinated-solvent-contaminated source zones.

PMID- 14717203
TI  - Comment on "Evidence for the absence of Staphylococcus aureus in the land applied
      biosolids".

PMID- 14717204
TI  - Comment on "Locating and quantifying PCB sources in Chicago: receptor modeling
      and field sampling".

PMID- 14717205
TI  - Atrial fibrillation: new horizons.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical
      practice. The understanding of the pathophysiology of AF has changed drastically
      during the last several decades. Recent observations have challenged the concept
      of the multiple circuit reentry model in favor of single focus or single circuit
      reentry models. Atrial electrical dysfunction provides a favorable substrate and
      transmembrane ionic currents are key determinants. Interest has also been
      generated in the role of angiotensin converting enzyme (ACE) inhibition in
      reversing the electrical and structural remodeling. Reverting to the sinus rhythm
      seems to be the best way for reverse remodeling of atria during atrial
      fibrillation. Antiarrhythmic drugs (AADs) are only modestly effective. Of these
      amiodarone seems to provide the most benefits. Drugs like verapamil and ACE
      inhibitors may also help as adjuvant therapies in the reverse remodeling of
      atria. Nonpharmacological methods have been used to control both rate and rhythm
      for patients with AF. Recently, there has been a surge in interest to focal
      ablation of atrial foci. Focal sources of AF are commonly found in pulmonary
      veins (PV). Ablation in pulmonary veins through identification of the earliest
      endocardial activation has met with variable success. Anatomical approaches have
      involved circumferential radiofrequency ablation of pulmonary vein ostia using
      novel techniques such as balloon based circumferential ultrasound ablation system
      and circular cryoablation catheter. Most recently the segmental approach is
      preferred because the myocardial fibers surrounding the PV are not continuous.
      Segments where musculature is present can be identified using high frequency
      depolarization signals recorded through multi-electrode loop catheter or even
      conventional catheters.

PMID- 14717206
TI  - Canine islet isolation, cryopreservation, and transplantation to nude mice.
AB  - BACKGROUND: Successful human islet transplantation has led to insulin
      independence in type 1 diabetes. Dogs constitute an animal model for preclinical
      studies. We present our recent experience in canine islet isolation,
      cryopreservation and transplantation. METHODS: Twenty-seven pancreases from
      mongrel dogs, weighing 9-31 kg, were removed. Each pancreas was digested with
      collagenase, and then purified by density gradients. Islet number and purity were
      counted, and the viability of isolated islets was assessed in vitro by static
      incubation, perifusion study and in vivo transplantation into nondiabetic or
      diabetic nude mice. Additionally. freshly isolated islets were cryopreserved for
      1 week, and then studied in vitro. RESULTS: The islet yield and purity were
      121,000 +/- 135,000 IEQ per pancreas and 81.4 +/- 1.2%, respectively. The
      stimulation index (insulin release in 300 mg/dl glucose/insulin release in 100
      mg/dl glucose) of the isolated islets was 6.6 +/- 1.9 (N = 7), and first and
      second phases of insulin secretion were demonstrated during perifusion study.
      After 1-week cryopreservation, the islet number decreased from 1,000 to 540 (N =
      1) and insulin content decreased from 50.95 to 39.23 microg/150 islets (N = 1).
      These islets maintained their insulin response to high glucose. Four weeks after
      transplantation, the grafts showed abundant beta-cells and significant insulin
      content. Normoglycemia was achieved in 14 of 23 diabetic recipients after
      transplantation with 2,000 freshly isolated islets. CONCLUSION: Canine islets
      isolated at our laboratory were viable and maintained their physiological
      function both in vitro and in vivo.

PMID- 14717207
TI  - Living arrangements and lifestyle satisfaction among the elderly in Chinese
      immigrant families: a preliminary study.
AB  - BACKGROUND: The aims of this preliminary study were to understand the
      relationship between the living arrangements and lifestyle satisfaction through
      investigating how choices of living arrangements impacted upon lifestyle
      satisfaction of elderly Chinese immigrants in London. METHODS: A qualitative
      research methodology with semi-structured, face-to-face and in-depth interviews
      was utilized with eight elderly couples of Chinese immigrant families from
      Vietnam and Hong Kong. RESULTS: The results indicated that the desirability of
      current lifestyle was associated with lifestyle satisfaction. Among 12
      participants who desired their current lifestyles, nine reported this having a
      "positive effect" on their lifestyle satisfaction, and no negative effects were
      reported. In comparison, the negative effects on lifestyle satisfaction were
      found among four participants who did not desire their current independent
      residence from their adult children. The reasons the participants desired or not
      their current lifestyles and the effects on their lifestyle satisfaction were
      explored qualitatively. The participants might consider family situations
      (finance, health, age, and kin network) to some extent. but not see them as key
      determinants in making decisions about living arrangements. However, the Chinese
      cultural beliefs in living arrangement choices were highly visible in their
      reports. CONCLUSION: The findings suggested that the elderly participants'
      desirability of their current lifestyles was positively associated with the level
      of lifestyle satisfaction. The issue of the living arrangements and lifestyle
      satisfaction of the elderly acquires new significance at a time when the
      population in Taiwan is aging, and the socio-economic and cultural changes are
      more radical than ever.

PMID- 14717208
TI  - Amniotic membrane grafts following excision of corneal and conjunctival
      intraepithelial neoplasia.
AB  - BACKGROUND: We evaluated the efficiency of amniotic membrane grafts (AMGs) for
      reconstructing the conjunctival surface following excision of corneal and
      conjunctival intraepithelial neoplasia (CIN). METHODS: This was a retrospective,
      noncomparative, interventional study. Five eyes in 5 patients were treated
      between April 1996 and September 2002 with the same procedure to apply amniotic
      membrane grafts after excising CIN. According to a standard protocol, the
      amniotic membrane was harvested and processed under sterile conditions. The
      amniotic membrane graft was applied over the excised bare scleral area and
      anchored with 10-0 nylon interrupted sutures. Patient data and clinical
      photographs were reviewed and analyzed. RESULTS: The mean follow-up period was 27
      (range, 6-69) months. Ocular surface healing was rapid and complete in all cases.
      No recurrence was found. CONCLUSION: Amniotic membrane graft is an effective and
      safe alternative adjunctive treatment for primary CIN. Further studies with
      longer follow-up are recommended to evaluate the risk of recurrence and other
      adverse effects.

PMID- 14717209
TI  - Early postoperative capsular block syndrome.
AB  - BACKGROUND: Postoperative capsular block syndrome (CBS) is a unique and rare
      complication of continuous curvilinear capsulorhexis (CCC). The purpose of this
      study was to analyze the clinical characteristics and results of early
      postoperative CBS. METHODS: Patients who developed early postoperative CBS after
      cataract surgery from October 1998 through September 2002 were retrospectively
      identified. All eyes underwent smooth phacoemulsification after anterior CCC. An
      intraocular lens (IOL) was implanted into the capsular bag. Neodymuim:YAG
      (Nd:YAG) laser peripheral anterior capsulotomy or posterior capsulotomy was
      performed when resolution did not occur or the intracoular pressure was elevated.
      RESULTS: Eight eyes of eight patients were included in the study. These patients
      presented with a shallow anterior chamber, anteriorly displaced IOL, distended
      capsular bag, and myopic shift within the first week after the surgery. One eye
      was associated with secondary angle-closure glaucoma. No CBS resolved without
      intervention during the follow-up period. The Nd:YAG laser peripheral anterior
      capsulotomy (4 eyes) and posterior capsulotomy (4 eyes) were successful in
      resolving the CBS in all eyes, and normalized the intraocular pressure in the eye
      with secondary angle-closure glaucoma. CONCLUSION: Postoperative CBS did not
      resolve spontaneously in most cases. Only a small percentage of early
      postoperative CBS was associated with secondary glaucoma. The Nd:YAG laser
      peripheral anterior capsulotomy and posterior capsulotomy were successful in
      treating postoperative CBS.

PMID- 14717210
TI  - Vertical banded gastroplasty: a simple, effective and safe surgery for morbid
      obesity.
AB  - BACKGROUND: The purpose of this study was to analyze the data of 92 patients who
      were treated with vertical banded gastroplasty (VBGP) for morbid obesity. We
      wanted to show that VBGP is a simple, effective and safe surgery for an
      experienced gastrointestinal surgeon. METHODS: From January 1994 through June
      2000, 92 patients with morbid obesity who were treated with VBGP were enrolled
      into this study. All associated data were corrected and analyzed. The gastric
      pouch was created with end-to-end anastomosis instrument (EEA-31) and two
      applications of thoracic anastomosis instrument (TA)90-4.8 or TA90-B. The outlet
      of the gastric pouch was 10 to 12 mm in diameter. The results were classified as
      excellent, good, fair, poor, and bad. RESULTS: Staple disruption occurred in four
      patients with two applications of TA90-4.8 at the beginning of the series. No
      surgical deaths occurred. Fifteen patients had excellent results. Thirty-eight
      patients had good results. Twenty-three patients had fair results. Only 16
      patients had poor or bad results. CONCLUSION: VBGP is a simple, effective and
      safe surgery for an experienced gastrointestinal surgeon in management of morbid
      obesity. The associated morbidity and mortality rates are low and the results are
      good.

PMID- 14717211
TI  - Results of curettage and high-speed burring for chondroblastoma of the bone.
AB  - BACKGROUND: Chondroblastomas of the bone are rare lesions. Most of these lesions
      can be successfully treated by curettage and bone grafting. However, a
      considerable rate of recurrence has been reported, especially in aggressive
      lesions. The purpose of this study was to report the results of 10 cases of
      chondroblastomas of the bone treated with curettage and high-speed burring.
      METHODS: Ten patients with histologically confirmed chondroblastoma of the bone
      were treated with curettage and high-speed burring between October 1991 and
      August 2000. There were 7 men and 3 women with an average age of 18.9 (range, 12
      to 30) years. Radiographically, 3 were classified as having aggressive lesions,
      and 7 were classified as having non-aggressive ones. For treatment, 8 of them had
      defects packed with either bone grafts or bone substitutes; 1 defect was packed
      with bone cement; and the other was left alone because the lesion was small.
      RESULTS: At an average follow-up period of 62 (range, 8 to 112) months, all
      patients had painless, normal function of the affected limb without local
      recurrence or distant metastasis. Complete healing of the lesion was seen in 8
      patients including the one without a bone graft. The lesion in 1 patient who had
      received bone cement remained unchanged radiographically. One patient experienced
      incomplete healing of the lesion, which was caused by inadequate packing of the
      bone substitute. CONCLUSION: Curettage and high-speed burring represent an
      effective method for the treatment of chondroblastoma of the bone whether in the
      non-aggressive or aggressive stage.

PMID- 14717212
TI  - Tension pneumoperitoneum following instrumental perforation of an obstructed
      esophagus in an infant.
AB  - A 4-month-old infant was diagnosed with esophageal atresia and tracheoesophageal
      fistula. He was admitted to our hospital because of progressive poor findings and
      repeated aspiration pneumonia after surgical repair. An esophagogram demonstrated
      severe esophageal stricture. Flexible endoscopic dilatation was performed under
      general anesthesia, but sudden onset respiratory distress and progressive
      abdominal distention were noted during the procedure. Abdominal radiographic
      study revealed severe pneumoperitoneum. Tension pneumoperitoneum after
      perforation of the obstructed esophagus is extremely rare but life threatening.
      We herein report our experience with the successful management of this
      complication in an infant.

PMID- 14717213
TI  - Multilocular renal cysts with renal cell carcinoma: report of four cases.
AB  - According to Bosniak's classification, renal cysts with moderate calcification,
      irregular margins, and thickened enhanced septa should raise a suspicion of
      malignancy. Diagnosis of multilocular renal cysts depends on their histological
      features. Since 1951, it has generally been considered that a multilocular renal
      cyst can change from a benign lesion to one which may be combined with malignant
      change. According to a report from Japan, multilocular renal cysts with renal
      cell carcinoma are uncommon, and the reported incidence was about 9%. A radical
      nephrectomy was performed for malignant change. Herein, we present 4 cases of
      multilocular cyst (Bosniak's class IV) with renal cell carcinoma and review the
      related literature for their pathogenesis and management.

PMID- 14717214
TI  - Perfluorocarbon liquid-assisted external drainage in the management of central
      serous chorioretinopathy with bullous serous retinal detachment.
AB  - The differential diagnosis of serous retinal detachment (RD) includes Vogt
      Koyanagi-Harada syndrome, severe hypertensive choroidopathy, posterior scleritis,
      multifocal choroiditis, metastatic tumor, and uveal effusion. Some cases of
      serous retinal detachment occur as a result of central serous chorioretinopathy
      (CSCR). Typical CSCR generally affects healthy middle-aged males and is
      characterized by localized serous RD of the neurosensory retina and retinal
      pigment epithelium in the macula that often spontaneously improve within 2 to 3
      months. On rare occasions, variant CSCR with bullous RD occurs which is
      frequently misdiagnosed. We report on a case of variant CSCR with severe bullous
      serous retinal detachment in the left eye that was initially treated at another
      hospital under the misdiagnosis of rhegmatogenous retinal detachment. Because the
      retinal detachment developed so fast that a laser could not be applied to all
      leaking spots, we performed a pars plana vitrectomy, pertluorocarbon liquid
      assisted external drainage, and final treatment with an endolaser. The retina was
      well attached after this management.

PMID- 14717215
TI  - Catheter-related superior vena cava syndrome complicated by chylothorax in a
      premature infant.
AB  - A premature infant experienced respiratory distress due to chylothorax. Contrast
      enhanced chest computed tomography showed superior vena cava (SVC) obstruction
      with collaterals, and surgery confirmed an obstruction of the SVC by
      intravascular fibrotic tissue and thrombi caused by placement of a central venous
      catheter. The respiratory distress improved after surgical intervention. In the
      differential diagnosis of acute respiratory distress, it is necessary to consider
      catheter-related chylothorax and SVC syndrome when a previously stable patient
      has an acute change in cardiopulmonary status, regardless of the duration of
      catheter use. Although often considered safe and easy, central venous catheter
      placement may result in complications. Using appropriate catheters and choosing
      proper insertion sites can minimize these events. Early diagnosis and treatment
      can be life-saving should complications occur.

PMID- 14717216
TI  - Diversity of visual pigments from the viewpoint of G protein activation-
      comparison with other G protein-coupled receptors.
AB  - The visual pigment present in the photoreceptor cells of the retina is a member
      of the family of G protein-coupled receptors and contains an 11-cis-retinal as a
      light-absorbing chromophore. Light induces conformational changes in the protein
      moiety of the visual pigment through cis-trans isomerization of the chromophore,
      which leads to the activation of a G protein-mediated signal transduction cascade
      that eventually generates an electrical response of the photoreceptor cells. So
      far, various types of visual pigments have been identified from a variety of
      photoreceptor cells and the structure-function relationship of visual pigments
      has been widely investigated by means of biophysical, biochemical and molecular
      biological techniques. Recent identifications of visual pigment-like proteins in
      the extra-ocular cells emphasize the importance of the visual pigment family as
      the photoreceptive molecules in not only visual but also non-visual
      photoreception. This article reviews the functional diversity of visual pigments
      from the viewpoint of the molecular mechanisms of photoreception and G protein
      activation. In addition, the similarity and difference of G protein activation
      mechanism between visual pigment and other G protein-coupled receptors are
      discussed for furthering our understanding of the common mechanism of G protein
      activation by G protein-coupled receptors.

PMID- 14717217
TI  - Photoisomerization and isomer-specific addition of water in hydroxystilbenes.
AB  - 3-Hydroxystilbene undergoes efficient addition of water on photoirradiation in
      acetonitrile-water binary solvent mixtures; behavior which is markedly different
      from that of 2- and 4-hydroxystilbene under similar conditions.

PMID- 14717218
TI  - Photoisomerization acceleration in retinal protonated Schiff-base models.
AB  - The results of new and recently reported CASSCF/6-31G* photoisomerization path
      computations of a series of models of the 11-cis retinal chromophore of the
      visual pigment rhodopsin are discussed. The results indicate that, with respect
      to the chromophore in vacuo, certain structural, intramolecular and environmental
      factors are capable of speeding up the excited-state decay associated with the
      cis --> trans isomerization motion. Using suitable protonated Schiff-base models,
      it is shown that three structural factors can potentially speed up the
      isomerization: (i) reducing the length of the conjugated chain, (ii) twisting of
      the hydrocarbon end of the conjugated chain with respect to the protonated Schiff
      base end and (iii) ring locking of the conjugated chain with an eight-membered
      ring. All these factors operate through increasing the slope of the excited-state
      energy surface and enhancing the coupling between stretching and torsional modes.
      We argue that the protein catalysis seen in rhodopsin may, at least partly,
      exploit the same principles.

PMID- 14717219
TI  - Isomerization around a C=N double bond and a C=C double bond with a nitrogen atom
      attached: thermal and photochemical routes.
AB  - The Longuet-Higgins phase change theorem is used to show that, in certain
      photochemical reactions, a single product is formed via a conical intersection.
      The cis-trans isomerization around the double bond in the formaldiminium cation
      and vinylamine are shown to be possible examples. This situation is expected to
      hold when the reactant can be converted to the product via two distinct
      elementary ground-state reactions that differ in their phase characteristics. In
      one, the total electronic wavefunction preserves its phase in the reaction; in
      the other, the phase is inverted. Under these conditions, a conical intersection
      necessarily connects the first electronic excited state to the ground state,
      leading to rapid photochemical isomerization following optical excitation.
      Detailed quantum chemical calculations support the proposed model. The
      possibility that a similar mechanism is operative in other systems, among them
      the rapid photo-induced cis-trans isomerization of longer protonated Schiff bases
      (the parent chromophores of rhodopsins), is discussed.

PMID- 14717220
TI  - Spectral and photophysical characteristics of unsymmetric polymethine dyes as
      model compounds for the colour shift of visual pigments.
AB  - Selectively bridged unsymmetric cyanines (dimethylamino-vinyl-benzothiazolium
      dyes) have been studied with respect to their photophysical properties using
      steady-state and time-resolved fluorescence. The nonradiative deactivation
      channels strongly depend on the bridging pattern and can be enhanced or slowed
      down, with the changes mainly connected to the Arrhenius pre-exponential factor,
      reflecting the photochemical pathways. The spectral shifts, on the other hand,
      are independent of the bridging pattern and are correlated with the compound's
      position on a donor acceptor axis including ideal polymethines. Using this model,
      the colour shift of visual pigments can be explained as an effect of the internal
      (protein-induced) electric field on the retinal Schiff base, likewise an
      unsymmetric polymethine dye system.

PMID- 14717221
TI  - New fluorescent probes for visual proteins. Part II. 5-(Oxo)penta-2,4-dienyl-p
      (N,N-dimethylamino)benzoate.
AB  - A new dual-fluorescent compound, 5-(oxo)penta-2,4-dienyl-p-(N,N
      dimethylamino)benzoate (1), a derivative of dimethylaminobenzoic acid, has been
      synthesised and studied photophysically. This compound continues the series of
      potential fluorescent probes for visual and proton-pumping opsin proteins. The
      photophysical behaviour of this molecule, including charge-transfer interaction
      in the ground state and dual-fluorescence emission, is similar to that of the
      previously studied analogue cis-3-(oxo)propenyl-p-(N,N-dimethylamino)benzoate
      (cis-2). The presence of several theoretically calculated conformers of compound
      2 was suggested to be responsible for the observed strongly red-shifted
      absorption and excitation wavelength dependence. These photophysical anomalies
      were also observed for molecule 1, though the models put forward to explain them
      in the cases of 1 and 2 are rather different. Based on theoretical calculations
      and experimental results, we propose that some of the stable conformers might be
      connected with either a charge-transfer complex or mesomeric interactions in the
      ground state. Upon changing the electronic nature of the oxo-pentadienyl acceptor
      moiety, e.g. protonation, chemical or biochemical reaction, the charge-transfer
      absorption disappears, which leads to a dramatic increase in the fluorescence
      quantum yield.

PMID- 14717222
TI  - A green cone-like pigment in the 'blind' mole-rat Spalax ehrenbergi: functional
      expression and photochemical characterization.
AB  - The degenerate subcutaneous eye of the blind mole rat belonging to the Spalax
      ehrenbergi superspecies has been shown to contain a long wavelength sensitive
      (LWS) cone pigment. Baculovirus expression of this LWS pigment and subsequent
      IMAC purification yields a photosensitive protein, that according to absorbance
      maximum (530 +/- 2 nm), kinetics of late phototransitions, and transducin
      activation, has all characteristics of a functional green cone pigment. The
      absorbance spectrum of the Spalax pigment is strongly red-shifted relative to the
      very homologous mouse, rabbit and rat green cone pigments (508-510 nm). Also in
      contrast to the rodent pigments, the Spalax pigment exhibits anion-dependent
      spectral properties, displaying a 12 nm blue-shift upon substitution of chloride
      ions by nitrate ions. Finally, the slow part of the photocascade deviates in some
      aspects from that of sighted mammals. The possible relevance of these findings
      for the evolutionary adaptation of Spalax to a subterranean ecotope is discussed.

PMID- 14717223
TI  - A step-by-step model of phototransduction cascade shows that Ca2+ regulation of
      guanylate cyclase accounts only for short-term changes of photoresponse.
AB  - A mathematical model of the vertebrate phototransduction mechanism was designed
      in a modular fashion, in that increasingly complex behaviors can be turned on and
      off to evaluate the relative involvement of all elements of the phototransduction
      cascade. The problem was approached by starting with a minimum model in which the
      intracellular cGMP concentration ([cGMP]i) was determined by guanylate cyclase
      (GC), whose activity was assumed not to be regulated by any factor (such as Ca2+)
      and by phosphodiesterase (PDE), whose activity was assumed to be proportional to
      the light intensity. All dependences were subsequently introduced, i.e. the
      equations describing PDE activation in detail, the Ca2+ regulation of GC and the
      action of intracellular Ca2+ buffers. The simulations and fits show that a high
      gain, smooth time- and light-dependent PDE activation, a Ca2+-dependent GC, and a
      Ca2+-dependent buffer mechanism are required to account for the flash response
      kinetics in the dark and on dim backgrounds of light, and the effect of exogenous
      Ca2+ buffers to produce responses characterized by slow and damped oscillations
      and to enhance the low-frequency noise. However, it was not possible to find any
      set of parameters able to simultaneously interpolate the waveform of the flash
      responses (in the dark and on a background of light) and the responses to steps
      of light. It is therefore concluded that at least one more shut-off mechanism
      (possibly not Ca-dependent) is necessary to fully account for the phenomenology
      of the light response in rod photoreceptors.

PMID- 14717224
TI  - Studies on adenylate kinase isoform bound to disk membranes of the rod outer
      segment of bovine retina.
AB  - An adenylate kinase (AK) activity modulated by calcium ion concentration has been
      found associated to the disk membranes of the rod outer segment of bovine retina.
      A maximum activity of about 80 nmol ATP produced per min per mg protein was found
      at physiological calcium concentrations. Preliminary experiments suggest that the
      membrane binding is presumably promoted by fatty acylation of the protein. In
      fact, a protein with a molecular weight corresponding to the disk adenylate
      kinase was recognized by a polyclonal antiserum against the first 15 N-terminal
      amino acids of AK1beta, a membrane-associated isoform of adenylate kinase, which
      belongs to the N-terminus myristoylated protein family. The adenylate kinase
      activity was also measured directly on the protein band transferred to
      nitrocellulose by Western blot.

PMID- 14717225
TI  - Difference spectra measurement of squid rhodopsin in the submillimeter wave
      region.
AB  - Theoretical studies by computer simulation have shown that vibrational modes,
      which depend on the subdomain motions of proteins, are located in the
      submillimeter wave region (i.e., 10-100 cm(-1)], 0.3-3 THz). We have successfully
      observed, by measuring the difference spectrum between squid rhodopsin and
      metarhodopsin to avoid water absorption, that squid rhodopsin shows its
      absorption features in this region. Our experimental results show that a native
      protein in solution indicates not only an absorbent property in this region but
      also an actual change of absorption with changes in protein conformation.

PMID- 14717226
TI  - Health benefits of solar UV-B radiation through the production of vitamin D.
      Comment and response.

PMID- 14717227
TI  - The relationship between serum VEGF concentration and prognosis of lung cancer.
AB  - BACKGROUND: VEGF is an important factor for angiogenesis. Although many previous
      studies have reported an increased serum VEGF concentration in various malignant
      tumors, there are few studies on the relationship between serum VEGF
      concentration and its prognosis. This study investigated whether serum VEGF
      concentration is a prognostic indicator for lung cancer. METHODS: Using the ELISA
      kit, we measured the serum VEGF concentrations of 86 patients diagnosed with lung
      cancer on histologic examination. With a cut off value of 686 pg/mL, the patients
      were classified as low-concentration (< 686 pg/mL, n=58) or high-concentration (>
      or = 686 pg/mL, n=28) based on their mean serum VEGF concentration values to
      compare survival rates, and serum VEGF concentrations for different histologic
      types and stages. RESULTS: There was no significant difference in serum VEGF
      concentration based on stage and histologic type between the two groups.
      Moreover, there was no significant difference in survival rate between the high
      concentration and low-concentration groups (p=0.86). CONCLUSION: This study
      demonstrates that serum VEGF concentration is not associated with the prognosis
      of lung cancer.

PMID- 14717229
TI  - Clinical features of Plasmodium vivax malaria.
AB  - BACKGROUND: Since its reemergence in 1993, a number of cases of Plasmodium vivax
      malaria have been reported in Korea. We analyzed the cases of malaria patients
      living in Chuncheon and its neighboring communities, to characterize its clinical
      manifestations and laboratory findings, and to identify any differences between
      our clinical findings and those of previous studies. METHODS: We reviewed the
      clinical records of cases that were confirmed as malaria by peripheral blood
      smear at Chuncheon Sacred Heart Hospital from July 1998 to September 2001.
      RESULTS: Forty-four cases were included in the study. All patients were infected
      with Plasmodium vivax, and presented with high fever; however, tertian fever
      developed in only 15 patients (35.7%). A number of cases showed various symptoms,
      which included headache, abdominal pain, nausea and vomiting. Of the 44 cases
      identified, 41 (93.2%) developed malaria between June and September.
      Thrombocytopenia was a prominent finding in 75% of the cases at diagnosis, but
      resolved during or after therapy. Other laboratory abnormalities such as, anemia,
      elevated transamines, coagulopathies, and elevated lactose dehydrogenase (LDH)
      were also noted. Cerebrospinal fluid (CSF) studies were performed in five cases,
      one of which showed pleocytosis in the CSF. CONCLUSION: We noted only 15 patients
      (35.7%) with tertian fever; the other patients showed variable fever patterns.
      Thrombocytopenia was the most prominent laboratory finding. Therefore, we suggest
      that malaria should be included in the differential diagnosis of febrile diseases
      with an onset between June to and September, regardless of the pattern of the
      fever.

PMID- 14717228
TI  - Clinical features of bronchogenic large cell carcinoma confirmed by surgical
      resection.
AB  - BACKGROUND: To define the final outcome of large cell carcinomas (LCC) after
      surgical treatment, the histopathology, clinical features and follow-up results
      of 28 cases were reviewed. METHODS: Twenty eight patients, with LCC that
      underwent a surgical resection between 1986 and 2001, at the Severance Hospital,
      were retrospectively reviewed. We analyzed clinical data, radiological findings,
      pathologic findings, treatment modalities, and survival. RESULTS: The prevalence
      of LCC was 2.9% (29 cases) among the surgically resected primary lung cancer
      cases (1003 cases) during the 15 year period of the study. The mean age of the
      patients was 59 years old, with 25 male cases. There were 23 smokers, smoking an
      average of 33 pack years. A cough was the most frequent symptom. There were 15
      cases located in the peripheral part of the lung and 26 consisted of a lobulated
      mass. From a chest CT scan, 26 cases had necrotic portions, which appeared to be
      low density. The postoperative stages were IA, IB, IIB, IIIA and IV in 1 (3.6%),
      11 (39.3%) 8 (28.5%), 7 (25%), 1 case (3.6%), respectively. The concordance rate
      of the pre- and postoperative stage was 43%. The median survival time and 5 year
      survival rate were 54.5 months and 45%, respectively. CONCLUSION: Our results
      suggested that a LCC in the lung was predominant in males, and equally located at
      the center and periphery of the lung in the surgically resected cases. To define
      the treatment outcome and risk factors of a LCC of the lung, further multicenter
      studies are needed.

PMID- 14717230
TI  - Immunohistochemical expression of COX-2 in thyroid nodules.
AB  - BACKGROUND: Recent evidence indicates that elevated COX-2 expression is
      associated with the carcinogenesis of numerous neoplasms. In this study, we
      investigated COX-2 expression in various thyroid specimens in order to elucidate
      its physiological role in pathologic conditions, and to evaluate the efficiency
      of COX-2 protein expression as a molecular marker of malignancy in the thyroid
      gland. METHODS: COX-2 expression was studied immunohistochemically in 19
      papillary carcinomas, 8 follicular carcinomas, 14 follicular adenomas, 2 Hurthle
      cell carcinomas, 4 Hurthle cell adenomas, 8 nodular hyperplasias, 3 Graves'
      diseases, 3 Hashimoto's thyroiditis, 2 medullary carcinomas, 1 anaplastic
      carcinoma, and 20 normal thyroid tissues. RESULTS: COX-2 staining was not seen in
      any of the normal thyroid, Graves' disease, or nodular hyperplasia specimens. In
      contrast, COX-2 staining was observed in all of papillary carcinomas, Hashimoto's
      thyroiditis, Hurthle cell carcinomas, and Hurthle cell adenomas tissues.
      Moreover, 7 of 8 follicular carcinomas and 11 of 14 follicular adenomas showed
      COX-2 staining. CONCLUSION: These results indicate that COX-2 is not useful as a
      marker of malignancy. Since COX-2 expression was evident in follicular adenomas
      and in papillary and follicular carcinomas. Thus, the enzyme may be involved in
      the early process of thyroid tumorigenesis.

PMID- 14717231
TI  - What is the clinical significance of transudative malignant pleural effusion?
AB  - BACKGROUND: A few reports of transudative malignant effusion on a small number of
      patients have suggested the need to perform routine cytologic examination in all
      cases of transudative pleural effusion, whether encountered for malignancy or
      not. The purpose of this study was to investigate whether cytologic examination
      should be performed in all cases of transudative pleural effusion for the
      diagnosis of malignancy. METHODS: We performed a retrospective study of 229
      consecutive patients with malignant pleural effusion, proven either cytologically
      or with biopsy. In patients with transudative pleural effusion, we reviewed
      medical records, results of transthoracic echocardiography, fiberoptic
      bronchoscopy, chest X-ray, chest CT scan, and ultrasonogram of the abdomen. These
      data were examined with particular attention to identifying whether or not the
      malignancy was suggested on chest X-ray, examining the involvement of the
      superior vena cava, great vessels, and lymph nodes, determining the presence of
      pericardial effusion, and observing the endobronchial obstruction. RESULTS:
      Transudative malignant pleural effusion was observed in seven (3.1%) of the 229
      patients, and was caused either by the malignancy itself (6 patients) or by
      coexisting cardiac diseases (1 patient). All the patients showed evidence
      suggesting the presence of malignancy at the time of initial thoracentesis, which
      facilitated the decision of most clinicians on whether to perform cytologic
      examination for the diagnosis of malignancy. CONCLUSION: Therefore, in all cases
      of transudative pleaural effusion, no clinical implications indicating malignancy
      were found on cytologic examination.

PMID- 14717232
TI  - Segmental groove pancreatitis: report of one case.
AB  - Groove pancreatitis is a special form of chronic pancreatitis in which scarring
      is found mainly in the groove between the pancreatic head, duodenum, and common
      bile duct. Preoperative differentiation between groove pancreatitis and
      pancreatic cancer is difficult. Here we report one case of segmental groove
      pancreatitis diagnosed by clinical and radiological features. The patient was a
      46-year old man with severe abdominal pain, weight loss, and a long history of
      alcohol abuse. Computed tomography revealed swelling of the pancreatic head and a
      heterogeneously enhanced low-density lesion in the groove. MR images revealed a
      mass in the groove that had a low signal on T1-weighted images and a low signal
      relative to the pancreatic head on T2-weighted images. T1-weighted images on
      dynamic study showed the medial wall thickening of descending duodenum, several
      small cysts in the groove and thickened duodenal wall. The patient has been under
      conservative treatment for 2 months and his severe abdominal pain has improved.

PMID- 14717233
TI  - A case of Mallory-Weiss syndrome complicating pregnancy in a patient with
      scleroderma.
AB  - The majority of patients with scleroderma have gastrointestinal involvement, and
      a few experience gastrointestinal hemorrhage, however, gastrointestinal
      hemorrhage due to Mallory-Weiss syndrome is very rare. We report upon a 24-year
      old pregnant woman with scleroderma who had gastrointestinal hemorrhage due to
      Mallory-Weiss syndrome.

PMID- 14717234
TI  - Minimally dilated obstructive nephropathy initially suspected as pre-renal
      azotemia in a kidney donor with volume depletion.
AB  - Although ultrasonography is regarded as the gold standard in the diagnosis of
      obstructive nephropathy, dilatation is sometimes not observed by ultrasonography.
      We report upon a case of minimally dilated obstructive nephropathy due to an
      ureter stone in a kidney donor with volume depletion. A 54-year-old man was
      admitted due to anuria and abdominal pain of 2 days duration. Ten years
      previously, his right kidney was donated for transplantation, and one month
      before admission, he abstained from all food except water and salt, for 30 days
      for religious reasons. He had lost 8 kg of body weight. On admission, he had
      clinical signs of volume depletion, i.e., a dehydrated tongue and decreased skin
      turgor. Laboratory data confirmed severe renal failure, his blood urea nitrogen
      level was 107.3 mg/dL, and his serum creatinine 16.5 mg/dL. The plain X-ray was
      unremarkable and ultrasonography showed only minimal dilatation of the renal
      collecting system. On follow-up ultrasonography, performed on the 5th hospital
      day, the dilatation of the collecting system had slightly progressed and a small
      stone was found at ureter orifice by cystoscopy. Removal of stone initiated
      dramatic diuresis with a rapid return of renal function to normal by the third
      day.

PMID- 14717235
TI  - Systemic lupus erythematosus associated with familial moyamoya disease.
AB  - We report on a 13-year-old female with systemic lupus erythematosus (SLE) who
      exhibited symptoms of severe migraine and familial moyamoya disease. Cerebral
      magnetic resonance angiography (MRA) showed stenosis and occlusion of the
      bilateral internal carotid arteries associated with the development of collateral
      circulation (moyamoya vessels). In a child, as in this case, headaches with
      cerebral infarction associated with moyamoya disease are unusual. Few cases of
      SLE associated with familial moyamoya disease have been reported, with no
      previous reports of such cases from Korea. There were no evidences of
      antiphospholipid syndrome, and activity of SLE or other risk factors for cerebral
      occlusion were also absent.

PMID- 14717236
TI  - Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.
AB  - Rhabdomyolysis is a rare complication that emerges in a variety of infectious
      diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old
      female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and
      acute renal failure. On admission, an eschar, which is characteristic of
      tsutsugamushi infection, was found on her right flank area. Moreover, her
      tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine
      phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to
      myoglobinuria are consistent with indications of rhabdomyolysis and acute renal
      failure due to tsutsugamushi infection. Her health improved without any residual
      effects after treatment with doxycyclin and hydration with normal saline.

PMID- 14717237
TI  - A case of relapsing polychondritis associated with myelodysplastic syndrome with
      erythroid hypoplasia/aplasia.
AB  - Relapsing polychondritis (RP) is a rare multisystem disorder. Myelodysplastic
      syndrome (MDS) with erythroid hypoplasia/aplasia is a rare form of
      myelodysplasia. Several cases of RP associated with MDS have recently been
      described. However, RP associated with MDS with erythroid hypoplasia/aplasia has
      never been reported. There was only one case report of polymyalgia rheumatica
      associated with MDS with erythroid hypoplasia/aplasia. In this study, we report a
      79-year-old patient with RP, who developed MDS subtype refractory anemia (RA)
      with erythroid hypoplasia/aplasia, a very characteristic subtype of MDS.

PMID- 14717238
TI  - Loffler's syndrome associated with Clonorchis sinensis infestation.
AB  - In 1932, Loffler described a syndrome of self-limiting, transient pulmonary
      infiltrates associated with peripheral blood eosinophilia and mild pulmonary
      symptoms. A number of conditions are related to pulmonary eosinophilia or
      pulmonary infiltration with eosinophilia. Especially, parasitic infestations are
      often related to pulmonary eosinophilia, but only two cases associated with
      Clonorchis sinensis have been anecdotally reported in English literature. Here we
      report a case of migrating pulmonary eosniophilic infiltrations associated with
      Clonorchis sinensis that was successfully treated with praziquantel.
      Clonorchiasis should be considered in patients with marked eosinophilia and
      pulmonary infiltrations.

PMID- 14717239
TI  - A typical Korean case of Carney complex.
AB  - Carney complex is a multiple neoplasia syndrome, inherited in an autosomal
      dominant manner, that is characterized by lentigines, cardiac myxoma, and
      numerous endocrine and other tumors, including primary pigmented nodular
      adrenocortical disease. Here, we describe a typical case of Carney complex in a
      27-year-old female who exhibited spotty skin pigmentation on the lips, oral
      mucosa, fingers, and toes and several manifestations of Cushing's syndrome due to
      primary pigmented nodular adrenocortical disease. She also had pituitary adenoma,
      breast tumor and thyroid nodule. Only a few cases of this disorder have been
      reported in the Korean literature. All of them, however, had only two components
      of Carney complex: composed of skin pigmentation and primary pigmented nodular
      adrenocortical disease. Therefore, the present case seems to be the first true
      case of Carney complex reported in Korea.

PMID- 14717240
TI  - Nature, nurture, and development: from evangelism through science toward policy
      and practice.
AB  - During the second half of the 20th century there was an immense increase in both
      empirical findings on, and conceptual understanding of, the effects of nature,
      nurture, and developmental processes on psychological functioning--both normal
      and abnormal. Unfortunately, the good science has also been accompanied by
      excessive polarizing claims and by unwarranted extrapolations. This article
      provides a summary review of the real gains in knowledge, outlines some of the
      misleading claims, and notes the potential for research and for science-led
      improvements in policies and practice. The need to bring about a better
      interpretation of genetic, psychosocial, and developmental research strategies
      and theoretical concepts is emphasized.

PMID- 14717241
TI  - Perception of kinetic illusory contours by two-month-old infants.
AB  - Perception of kinetic illusory contours by 2-month-old infants was explored with
      sparse random-dot displays depicting an illusory shape against a background. In
      Experiment 1, 24 infants were habituated to a shape specified by accretion and
      deletion of background texture and relative motion, and exhibited a novelty
      preference when presented with luminance-defined familiar and novel shapes.
      Subsequent experiments explored kinetic cues in isolation. In Experiment 2 (n =
      24), relative motion information was removed, leaving accretion and deletion of
      texture and luminance cues, and in Experiment 3 (n = 24), only relative motion
      information was available. In both these experiments the novelty preference
      obtained in Experiment 1 was replicated. Results from a control condition (n =
      12) mitigated against the likelihood of an inherent preference for either of the
      test shapes. These findings reveal an early capacity to perceive shape solely
      from kinetic information, and suggest a mechanism geared toward spatiotemporal
      boundary formation that is functional shortly after birth. Theories of
      development of edge and motion discrimination are discussed.

PMID- 14717242
TI  - Who's in the mirror? Self-other discrimination in specular images by four- and
      nine-month-old infants.
AB  - This research investigated the early determinants of self-other discrimination in
      infancy. Ninety-six 4- and 9-month-old infants were placed facing a live image
      either of themselves or of another person (experimenter) mimicking them. The
      specular image was either contingent (on-line), or contingent with a 2-s delay.
      After a first 1-min presentation, the video image of either the self or the other
      was suddenly frozen for 1 min (still-face episode). This was followed by a last
      minute of live presentation. From 4 months of age, infants appeared to perceive
      and act differentially when facing the specular image of themselves or the
      mimicking other. In general, infants tended to smile more, look more, and have
      more protracted first-look duration toward the mimicking other compared with the
      self. Developmentally, 9-month-olds showed markedly more social initiatives
      toward the mimicking other compared with the self during the still-face episode.
      In all, these results indicate that infants develop self-other discrimination in
      specular images long before mirror self-recognition, which is typically reported
      by the second year. Discrimination of the self from other is interpreted as a
      precursory ability and a perceptual foundation of later conceptual self
      development.

PMID- 14717243
TI  - A longitudinal study of visual expectation and reaction time in the first year of
      life.
AB  - Developmental change and stability of visual expectation and reaction times (RT)
      were examined at 5, 7, and 12 months in a longitudinal sample of term and preterm
      infants (birthweight <1,750 g). Using the traditional 200-ms cut-point to
      separate anticipatory from reactive saccades, RTs (and their standard deviations)
      declined markedly over age, whereas anticipations increased. Those infants who
      had faster RTs were more likely to anticipate upcoming events and were more
      attentive (fewer trials off-task and less response variability). Crossage
      stability was modest for most measures from 5 to 7 and 7 to 12 months, but rarely
      significant from 5 to 12 months. When the cut-point was lowered to 150 ms (to
      accommodate recent concerns that the higher cut-point may misclassify some true
      RTs as anticipations), the age-related increase in anticipations disappeared.
      Thus, although the results indicate marked increases in processing speed with
      age, evidence for increasing anticipations is equivocal. Findings were similar
      for preterm and term infants.

PMID- 14717244
TI  - Sleep and adjustment in preschool children: sleep diary reports by mothers relate
      to behavior reports by teachers.
AB  - Prior literature suggests that there may be relations between children's sleep
      disorders or inadequate amounts of sleep and behavioral adjustment. Most relevant
      studies concern clinical populations, however, and relatively few concern
      community populations. Moreover, previous studies have not addressed empirically
      the possible role of family functioning as a factor in the relation between
      children's sleep and adjustment. The present study, conducted in a predominantly
      low-income, community sample (N = 202), measured 4- to 5-year-old children's
      sleep patterns through daily logs kept by mothers, and measured family stress and
      parenting practices through detailed, multifaceted interviews and incidental
      observations of parent-child interactions. Children's adjustment, both positive
      and negative, was measured through preschool teacher reports on multiple
      occasions. A structural equation model showed that disrupted child sleep patterns
      (variability in reported amount of sleep, variability in bedtime, and lateness of
      bedtime) predicted less optimal adjustment in preschool, even after considering
      the roles of family stress and family management practices.

PMID- 14717245
TI  - Salivary cortisol as a predictor of socioemotional adjustment during
      kindergarten: a prospective study.
AB  - This study, based on a sample of 172 children, examined the relation between
      average afternoon salivary cortisol levels measured at home at age 4.5 years and
      socioemotional adjustment a year and a half later, as reported by mothers,
      fathers, and teachers. Cortisol levels were hypothesized to be positively
      associated with withdrawal-type behaviors (e.g., internalizing, social wariness)
      and inversely related to approach-type behaviors, both negative and positive
      (e.g., externalizing, school engagement). Higher cortisol levels at age 4.5
      predicted more internalizing behavior and social wariness as reported by teachers
      and mothers, although child gender moderated the relation between cortisol and
      mother report measures. An inverse relation was found between boys' cortisol
      levels and father report of externalizing behavior. A marginal inverse relation
      was found between child cortisol levels and teacher report of school engagement.
      Behavior assessed concurrently with cortisol collection did not account for the
      prospective relations observed,suggesting that cortisol adds uniquely to an
      understanding of behavioral development.

PMID- 14717246
TI  - Attention to novel objects during verb learning.
AB  - Three experiments provided evidence that 3.5- to 4-year-old English-speaking
      children (N = 72) attend to the appearances of novel objects, not only when they
      hear a novel noun, but also when they hear a novel verb. Children learning nouns
      in the context of novel, moving objects attended exclusively to the appearances
      of objects, even though nouns were also related to the motions of those objects.
      Children learning verbs attended equally to the appearances of objects and their
      motions. The latter result contrasted with the results from adults (N = 20), who
      focused more strongly on motions than on the appearances of objects when learning
      verbs. When familiar objects were instead employed, child verb learners attended
      more to motions than to the appearances of objects. Children may attend to novel
      objects during verb learning because knowledge of an object may be prerequisite
      to understanding what a verb means in the context of that object.

PMID- 14717247
TI  - Relation of maternal cognitive stimulation, emotional support, and intrusive
      behavior during Head Start to children's kindergarten cognitive abilities.
AB  - The current study examined how parental cognitive stimulation, emotional support,
      and intrusiveness measured during children's prekindergarten year were related to
      children's verbal and nonverbal abilities 1 year later. Participants were 110
      Head Start children and their caregivers from primarily rural and low-income
      backgrounds. Analysis of children's scores on the McCarthy Scales of Children's
      Abilities confirmed the predictive utility of cognitive stimulation, emotional
      support, and intrusive behavior for perceptual scores (20% of the unique
      variance) as well as the predictive utility of emotional support and intrusive
      behavior for verbal scores (15% of the unique variance). Parental emotional
      support during guidance of problem solving (positive feedback) explained
      statistically significant unique variance in children's perceptual scores beyond
      other measures of emotional support. Cognitive stimulation moderated the relation
      between positive feedback and perceptual scores. Although other syntactic forms
      of maternal utterances such as commands did not explain statistically significant
      unique variance in children's scores beyond emotional support and intrusive
      behavior, mothers' questions did. Specific policy implications of the effects are
      discussed.

PMID- 14717248
TI  - Children's understanding of their research rights before and after debriefing:
      informed assent, confidentiality, and stopping participation.
AB  - This study explored children's understanding of their research rights in the
      context of an investigation of how children cope with peer provocation.
      Participants were 178 children (97 girls and 81 boys) who had finished the
      second, fourth, and sixth grades (average ages: 8, 10, and 12, respectively).
      After children agreed to take part in research on "how kids get along together,"
      as well as after debriefing, their perceptions of free assent, their
      understanding of what they would be doing and why, their belief in voluntary
      participation and freedom to withdraw, and their comprehension of confidentiality
      were assessed. The vast majority of participants gave assent freely and reported
      no undue pressure from their families or the experimenters to participate. Older
      children knew before participating in the research what their participation would
      involve, comprehended confidentiality, and understood the study's purpose after
      their participation, but second graders were less likely to understand these
      issues than fourth and sixth graders were. Following debriefing, children's
      understanding of their research rights was largely unchanged; most children still
      had difficulty describing the research goals.

PMID- 14717249
TI  - The contribution of emotionality and self-regulation to the understanding of
      children's response to multiple risk.
AB  - This study investigated the additive and interactive effects of multiple risk,
      emotionality, and self-regulation in predicting children's adjustment problems
      and positive adjustment using a community sample (N = 101) of children in third
      through fifth grades. Multiple measures of emotionality and self-regulation were
      used, including observational measures and mother and child report on
      questionnaires. Results indicated that questionnaire measures of emotionality and
      self-regulation predicted children's positive and negative adjustment over and
      above the effects of multiple risk, as well as resilience and vulnerability.
      Negative emotionality predicted adjustment problems, positive emotionality
      predicted positive adjustment, and self-regulation predicted both. In addition,
      observational measures of self-regulation moderated the association between
      multiple risk and adjustment such that children low in self-regulation were more
      vulnerable to multiple risk. The results suggest that emotionality and self
      regulation operate as additional risk and protective factors in multiple-risk
      models.

PMID- 14717250
TI  - Genetic and environmental influences in adolescent peer socialization: evidence
      from two genetically sensitive designs.
AB  - Harris argues that peer relationships are the chief determinants of personality
      development. Harris's thesis makes the behavioral genetic investigation of peer
      groups particularly timely. The present study examined genetic and environmental
      contribution to self-reported peer-group characteristics in two samples of
      adolescent siblings: 180 adoptive and nonadoptive sibling pairs from the Colorado
      Adoption Project, and 386 sibling pairs from the Nonshared Environment and
      Adolescent Development Study. Substantial genetic influence emerged for college
      orientation, with the remaining variance accounted for by nonshared environment.
      For delinquency, however, the majority of the variance was explained by nonshared
      environment. Although genetic influence was implicated for peer popularity in
      twin analyses, genetic factors were not important in explaining individual
      differences in nontwin siblings. These results suggest that although some
      dimensions of peers are somewhat mediated by genetic factors, nonshared
      environmental influence is substantial.

PMID- 14717251
TI  - Evaluation of a social contextual model of delinquency: a cross-study
      replication.
AB  - The present study empirically examined three theoretical approaches designed to
      predict risk for delinquency during adolescence: an individual difference
      perspective, a social interactional model, and a social contextual approach.
      Hypotheses derived from each perspective were tested using two independent
      samples of early adolescents followed over a 4-year period. Six-hundred sixty
      seven children (in sixth grade at Time 1), and their parents comprised the first
      sample (Project Family); and 451 children (in seventh grade at Time 1), their
      parents, and a close-aged sibling made up the second sample (Iowa Youth and
      Families Project). Results from a series of structural equation models suggested
      that a social contextual approach provided the best fit with the data across both
      samples and genders. Consistent with the social contextual approach, results
      indicated that a lack of nurturant and involved parenting indirectly predicted
      delinquency by increasing children's earlier antisocial behavior and deviant peer
      relationships; child antisocial behavior also predicted similar decreases in
      nurturant parenting over time. Both child antisocial behavior and deviant peer
      affiliations at Time 2 predicted delinquency 1 year later. Implications for
      theoretical development and future research priorities are discussed.

PMID- 14717252
TI  - Group identification in early adolescence: its relation with peer adjustment and
      its moderator effect on peer influence.
AB  - This study was conducted to test whether group identification (importance of the
      group to the individual) covaried with individual-group similarity on problem
      behavior; and whether group identification moderated peer group influence on the
      individual's development of delinquent behavior across a 1-year period. The level
      of reciprocated nominations within the individual's self-nominated group was
      controlled for in all analyses. Participants were 190 sixth and seventh graders
      (during the first year of the study) from the north of Italy. Level of
      reciprocated nominations within the group, but not identification, was found to
      covary with individual-group behavioral similarity (group behavior interacted
      with reciprocity of group nominations in predicting individual behavior). Group
      identification, but not reciprocated nominations, was found to moderate peer
      group influence on the individual's change in delinquent behavior, across 1 year.
      The individual's peer status within the classroom, level of reciprocated
      nominations, and gender all were related to the individual's level of group
      identification. Results are discussed in terms of understanding peer group
      influence on the individual.

PMID- 14717253
TI  - The ADHD spectrum and everyday life: experience sampling of adolescent moods,
      activities, smoking, and drinking.
AB  - Using an experience sampling methodology, the everyday lives of 153 adolescents
      with low, middle, or high levels of attention-deficit/hyperactivity disorder
      (ADHD) characteristics as assessed by either parent or teen were examined. Twice
      each hour, across two 4-day recording intervals, participants in a longitudinal
      study of stress and health risks logged their behaviors, moods, and social
      contexts. Those with high, in contrast to low, ADHD symptom levels recorded more
      negative and fewer positive moods, lower alertness, more entertaining activities
      relative to achievement-oriented pursuits, more time with friends and less time
      with family, and more tobacco and alcohol use. Fewer associations emerged with
      parent-defined than with teen-defined subgroups, although the differences in
      alertness, peer and family contexts, entertainment versus achievement activities,
      and substance use were consistent across sources. Even at subclinical levels,
      ADHD characteristics were associated with behavioral patterns and contexts that
      may promote peer deviancy training, unhealthy lifestyle behaviors, and
      vulnerability to nicotine dependence.

PMID- 14717254
TI  - Child emotionality and maternal responsiveness as predictors of reunion behaviors
      in the strange situation: links mediated and unmediated by separation distress.
AB  - Children's emotionality--fear, anger, and joy--observed outside of the
      relationship with the mother (in standard laboratory paradigms), and within that
      relationship (in mother-child interactions), and mothers' responsiveness, all at
      9 and 14 months, were examined as predictors of the reunion behaviors in the
      Strange Situation at 14 months in 112 children. Many predictors were linked to
      the reunion behaviors, but most of those relations were at least partially
      mediated by children's separation distress, which itself strongly predicted the
      reunion behaviors. Those relations were no longer significant when distress was
      controlled. Several links, however, remained significant, and they were
      unmediated by distress: Almost all involved measures assessed within the context
      of the mother-child relationship. In particular, possible markers of a suboptimal
      relationship (children's dampened joy and increased anger in interactions with
      the mother, poor maternal responsiveness) were associated with more avoidance and
      resistance upon reunion, even after accounting for the strong impact of distress.
      Studying how factors measured outside of and within early relationships influence
      the components of the attachment system may foster understanding of child
      behavior in the Strange Situation.

PMID- 14717255
TI  - Adolescents' working models and styles for relationships with parents, friends,
      and romantic partners.
AB  - This study examined the links among adolescents' representations of their
      relationships with parents, friends, and romantic partners. Sixty-eight
      adolescents were interviewed three times to assess their working models for each
      of these types of relationships. Working models of friendships were related to
      working models of relationships with parents and romantic partners. Working
      models of relationships with parents and romantic partners were inconsistently
      related. A similar pattern of results was obtained for self-report measures of
      relational styles for the three types of relationships. Perceived experiences
      were also related. Specifically, support in relationships with parents tended to
      be related to support in romantic relationships and friendships, but the latter
      two were unrelated. On the other hand, self and other controlling behaviors in
      friendships were related to corresponding behaviors in romantic relationships.
      Negative interactions in the three types of relationships also tended to be
      related. Taken together, the findings indicate that the representations of the
      three types of relationships are distinct, yet related. Discussion focuses on the
      nature of the links among the three.

PMID- 14717256
TI  - Parenting and development of one-year-olds: links with parental, contextual, and
      child characteristics.
AB  - A set of hypotheses derived from Belsky's process model of the determinants of
      parenting was tested in a sample of 129 Dutch parents with their 15-month-old
      infants. Parental ego-resiliency and education, partner support, and infant
      social fearfulness were found to explain significant and unique portions of
      variance in the observed quality of parental behavior, which, in turn, was linked
      to the infants' attachment security and cognitive development. Parental
      intelligence was both indirectly--through parenting--and directly related with
      infant Bayley Mental Developmental Index, whereas parental ego-resiliency was
      both indirectly and directly linked with infant Attachment Q-Set security.
      Belsky's claim that parents' personal resources are most effective and child
      characteristics are least effective in buffering the parenting system was not
      empirically confirmed.

PMID- 14717257
TI  - Unique and protective contributions of parenting and classroom processes to the
      adjustment of African American children living in single-parent families.
AB  - The unique contributions that parenting processes (high levels of monitoring with
      a supportive, involved mother-child relationship) and classroom processes (high
      levels of organization, rule clarity, and student involvement) make to children's
      self-regulation and adjustment were examined with a sample of 277 single-parent
      African American families. A multi-informant design involving mothers, teachers,
      and 7- to 15-year-old children was used. Structural equation modeling indicated
      that parenting and classroom processes contributed uniquely to children's
      adjustment through the children's development of self-regulation. Additional
      analyses suggested that classroom processes can serve a protective-stabilizing
      function when parenting processes are compromised, and vice versa. Further
      research is needed to examine processes in both family and school contexts that
      promote child competence and resilience.

PMID- 14717258
TI  - Are effective teachers like good parents? Teaching styles and student adjustment
      in early adolescence.
AB  - This study examined the utility of parent socialization models for understanding
      teachers' influence on student adjustment in middle school. Teachers were
      assessed with respect to their modeling of motivation and to Baumrind's parenting
      dimensions of control, maturity demands, democratic communication, and
      nurturance. Student adjustment was defined in terms of their social and academic
      goals and interest in class, classroom behavior, and academic performance. Based
      on information from 452 sixth graders from two suburban middle schools, results
      of multiple regressions indicated that the five teaching dimensions explained
      significant amounts of variance in student motivation, social behavior, and
      achievement. High expectations (maturity demands) was a consistent positive
      predictor of students' goals and interests, and negative feedback (lack of
      nurturance) was the most consistent negative predictor of academic performance
      and social behavior. The role of motivation in mediating relations between
      teaching dimensions and social behavior and academic achievement also was
      examined; evidence for mediation was not found. Relations of teaching dimensions
      to student outcomes were the same for African American and European American
      students, and for boys and girls. The implications of parent socialization models
      for understanding effective teaching are discussed.

PMID- 14717259
TI  - The impact of family obligation on the daily activities and psychological well
      being of Chinese American adolescents.
AB  - A daily diary method was employed to examine the extent to which Chinese
      adolescents in the United States assist and spend time with their families, and
      the implications of such behaviors for their involvement in other activities and
      psychological well-being. Adolescents (N = 140) completed checklists in which
      they reported their activities and psychological well-being every day for a
      period of 2 weeks. Adolescents showed a greater propensity to balance family
      obligations with their academic demands than with their social life with peers on
      a daily basis. Girls experienced slightly more daily conflict between activities
      than boys. Neither the extent of involvement in family obligations nor the
      balancing of family obligations with other activities were associated with
      psychological distress among adolescents. These findings demonstrate the complex
      manner in which adolescents from immigrant families attempt to combine their
      cultural traditions with selected aspects of American society on a daily basis.
      In contrast to the expectations of some observers, the youths in this study
      appeared to accomplish such an integration with little cost to their
      psychological well-being.

PMID- 14717260
TI  - Benefits of the Comprehensive Child Development Program as a function of AFDC
      receipt and SES.
AB  - The benefits for children at the Pittsburgh site of the federal Comprehensive
      Child Development Program (CCDP) were examined as a function of family welfare
      status (Aid to Families with Dependent Children; AFDC) and SES. The CCDP was the
      largest attempt by the federal government to provide two-generation, case
      managed, comprehensive services to low-income families. Participating families
      could set their own goals and choose services to achieve them, but relatively few
      services were directed specifically at children. Results showed that more
      Pittsburgh families in the CCDP treatment group (N = 120) left AFDC than in the
      control group (N = 120), consistent with results from a national evaluation of
      the CCDP. Children whose families were on AFDC regardless of treatment group had
      lower mental test scores, even after controlling for family SES, a result
      suggesting that AFDC receipt over and above income level was associated with
      poorer child mental performance. The CCDP was associated with higher children's
      mental scores plus improvements over time in achievement scores only for children
      in families who were not on AFDC, even after controlling for SES. Such parents
      were more likely to choose parenting and child goals and services, which in turn
      were associated with higher child mental scores. In contrast, parents who were on
      AFDC tended to choose adult-centered goals and services, which did not benefit
      children. Therefore, in contrast to the national evaluation, which found no
      benefits of the CCDP for children, these analyses showed that the CCDP did
      produce benefits for children whose parents were not on AFDC, who tended to
      choose parenting and child services.

PMID- 14717261
TI  - Improving medication adherence: pharmacists should take the lead.

PMID- 14717262
TI  - Counterfeit medications: the pharmacist's role in protecting the integrity of the
      medication supply.

PMID- 14717263
TI  - Improving adherence and persistence: a review and assessment of interventions and
      description of steps toward a national adherence initiative.
AB  - OBJECTIVES: To identify the effectiveness of adherence interventions reported in
      the literature, to identify interventions being conducted and/or sponsored by
      large chain pharmacies and pharmaceutical manufacturers, and to seek input from a
      panel of pharmacists who address adherence issues on a daily basis as to the
      steps that should be taken to advance a national initiative to increase awareness
      of the importance of and opportunities associated with medication adherence and
      persistence. MAIN OUTCOME MEASURE: Effectiveness of the adherence interventions
      reported in the literature. METHODS: First, a literature search was conducted
      using MEDLINE, International Pharmaceutical Abstracts, CINAHL, and PsycINFO.
      Keywords were medication or drug and compliance or adherence or persistence and
      control group. Second, pharmaceutical manufacturers and chain pharmacies were
      surveyed. Third, an advisory panel reacted to the research findings and
      formulated a series of action steps that could support or be part of a national
      initiative to increase adherence. RESULTS: Reported adherence-related
      interventions were grouped into five categories--adherence aids, refill or follow
      up reminders, regimen simplification, written and oral education, and
      comprehensive management. Median adherence increases ranged from 6% to 25% for
      these categories. Interviews with 10 chain pharmacies revealed that adherence is
      an important issue. Most chains have some form of adherence program in place, but
      current initiatives are product-focused rather than patient-focused. Interviews
      with 15 manufacturers revealed that they currently use a variety of adherence
      interventions and want to partner with pharmacies to implement and assess the
      initiatives. The advisory panel developed a series of action items for
      implementing a national adherence initiative. CONCLUSION: Comprehensive
      interventions can improve adherence and are mutually beneficial for patients,
      pharmacies, and manufacturers. Pharmacists must be able to assess patients'
      adherence, identify the reasons for nonadherence, and develop patient-specific
      interventions. Studies have shown that the most successful interventions have
      some follow-up component and address the underlying reason(s) for nonadherence.
      Pharmacies and pharmaceutical manufacturers have tried various adherence
      interventions, such as patient education and refill reminders. There is a growing
      sense that a national adherence initiative is needed to coordinate pharmacists'
      efforts to address this public health problem, and the American Pharmacists
      Association is well positioned to take a leadership role in such efforts.

PMID- 14717264
TI  - Acetaminophen overuse in the Ohio Medicaid population.
AB  - OBJECTIVE: To examine patterns of use of acetaminophen in patients with and
      without risk factors for hepatotoxicity in the Ohio Medicaid population. DESIGN:
      Retrospective, cross-sectional analysis of claims data. SETTING: Ohio. PATIENTS:
      Ohio Medicaid patients (n = 22,496) who received at least 6 prescriptions for
      acetaminophen from November 1998 through April 1999. MAIN OUTCOME MEASURE:
      Overuse of acetaminophen, defined as an average daily dose (ADD) greater than or
      equal to 4 grams/day or an ADD of greater than or equal to 3 grams/day along with
      diagnosis codes suggesting underlying liver dysfunction. RESULTS: We identified
      687 patients (3.05%) who received either greater than or equal to 4 grams/day or
      greater than or equal to 3 grams/day and had diagnosis codes suggesting
      underlying liver dysfunction (n = 128). CONCLUSION: Although the number is
      relatively small, some Ohio Medicaid patients are receiving acetaminophen doses
      that exceed safety recommendations. Because acetaminophen overuse is the leading
      cause of liver failure, health care professionals should be alert to the
      possibility of acetaminophen overuse.

PMID- 14717265
TI  - Development and assessment of a short instrument for assessing dietary intakes of
      calcium and vitamin D.
AB  - OBJECTIVE: To validate a short food frequency screening instrument designed to
      assess dietary intakes of calcium and vitamin D. DESIGN: Cross-sectional surveys
      and food diaries. PARTICIPANTS: Twenty-seven university employees. MAIN OUTCOME
      MEASURES: Calcium and vitamin D intakes of participants were assessed using three
      instruments: a 7-day food diary, the Block-National Cancer Institute Health
      Habits and History Questionnaire (HHHQ), and a short screening instrument derived
      from the HHHQ. The accuracy of participants' reports of calcium and vitamin D
      intakes on the HHHQ and short screening instrument were checked against the food
      diaries. The validity of the full survey and the screening instrument were judged
      according to their correlation with the food diaries. RESULTS: Estimates of
      calcium and vitamin D intakes derived from the 7-day food diary and the short
      screening instrument were significantly correlated (r = 0.66 and 0.72,
      respectively, P < .001). The mean differences between estimates derived from the
      short screening instrument and those derived from the 7-day food diary were 223
      mg/day for calcium and 47 IU/day for vitamin D. The positive predictive value of
      the short screening instrument in identifying individuals with low nutrient
      intakes, as assessed by the 7-day food diary, was 91.7% for calcium and 100.0%
      for vitamin D. CONCLUSION: The short screening instrument provides reasonably
      accurate estimates of calcium and vitamin D intakes. Although it cannot replace
      more comprehensive nutritional assessments, the screening instrument may provide
      quick assessments of calcium and vitamin D intakes. Given that many individuals
      consume suboptimal levels of these nutrients, pharmacists may use the screening
      instrument to evaluate patients' needs for calcium and/or vitamin D supplements
      and, thus, reduce their risk for developing osteoporosis.

PMID- 14717266
TI  - Pharmacists' opinions regarding level of involvement in emergency preparedness
      and response.
AB  - OBJECTIVE: To assess opinions of pharmacist-members of the American Pharmacists
      Association Academy of Pharmacy Practice and Management (APhA-APPM) regarding the
      appropriate level of pharmacists' involvement in emergency preparedness and
      response activities and to determine whether opinions differed according to
      demographic characteristics. DESIGN: Cross-sectional, descriptive, Web-based
      survey. SETTING: United States. PARTICIPANTS: Five hundred eighteen APhA-APPM
      member-pharmacists. MAIN OUTCOME MEASURES: Responses to survey questions.
      RESULTS: Respondents to our survey indicated that pharmacists should have a high
      level of involvement in emergency preparedness and response activities.
      Traditional pharmacy practice activities (such as medication preparation and
      dispensing) and patient education were the most highly supported roles for
      pharmacists. Newer activities such as surveillance, vaccine administration, and
      mobilization were also strongly supported. Demographic characteristics, such as
      age, sex, degree, state of residence, practice setting, and employment setting,
      did not influence respondents' opinions. The only characteristic that influenced
      pharmacist opinions was previous participation in local and/or state emergency
      preparedness and response activities. Compared with other respondents,
      pharmacists who participated in these activities gave higher ratings to these
      possible roles for pharmacists: surveillance, triage/evaluation, community
      planning and preparation, mobilization, and training of others. CONCLUSION:
      Pharmacist-members of APhA-APPM who responded to this survey believe that
      participating in public health activities related to emergency preparedness and
      response is important for members of the pharmacy profession.

PMID- 14717267
TI  - Disequilibrium and human capital in pharmacy labor markets: evidence from four
      states.
AB  - OBJECTIVES: To estimate the association between pharmacists' stocks of human
      capital (work experience and education), practice setting, demographics, and wage
      rates in the overall labor market and to estimate the association between these
      same variables and wage rates within six distinct pharmacy employment sectors.
      Wage estimation is used as a proxy measure of demand for pharmacists' services.
      DESIGN: Descriptive survey analysis. SETTING: Illinois, Minnesota, Ohio, and
      Wisconsin. PARTICIPANTS: Licensed pharmacists working 30 or more hours per week.
      INTERVENTION: Analysis of data collected with cross-sectional mail surveys
      conducted in four states. MAIN OUTCOME MEASURES: Hourly wage rates for all
      pharmacists working 30 or more hours per week and hourly wage rates for
      pharmacists employed in large chain, independent, mass-merchandiser, hospital,
      health maintenance organization (HMO), and other settings. RESULTS: A total of
      2,235 responses were received, for an adjusted response rate of 53.1%.
      Application of exclusion criteria left 1,450 responses from full-time pharmacists
      to analyze. Results from estimations of wages in the pooled sample and for
      pharmacists in the hospital setting suggest that advanced training and years of
      experience are associated positively with higher hourly wages. Years of
      experience were also associated positively with higher wages in independent and
      other settings, while neither advanced education nor experience was related to
      wages in large chain, mass-merchandiser, or HMO settings. CONCLUSION: Overall,
      the market for full-time pharmacists' labor is competitive, and employers pay
      wage premiums to those with larger stocks of human capital, especially advanced
      education and more years of pharmacy practice experience. The evidence supports
      the hypothesis that demand is exceeding supply in select employment sectors.

PMID- 14717269
TI  - Impact of Internet use on business functions in independent community pharmacies.

PMID- 14717268
TI  - Counterfeit pharmaceuticals: current status and future projections.
AB  - OBJECTIVES: To examine the problem of counterfeit drugs and its effects around
      the world, to consider the likely directions the problem will take, and to
      propose options for controlling or mitigating the problem. DATA SOURCES: Recently
      published clinical literature identified through review of articles abstracted at
      MEDLINE. Search terms were counterfeiting, counterfeit drugs, substandard drugs,
      fake drugs, world counterfeiting, and counterfeit pharmaceuticals. Further
      information was abstracted from an array of informational sources, including
      magazines such as Business Week, newspapers such as the International Herald
      Tribune, National Public Radio news reports, pharmaceutical company press
      releases, and information from the World Health Organization. STUDY SELECTION:
      Multiple reviewers were used to retrieve relevant and current data. DATA
      EXTRACTION: Relevant data were extracted independently by multiple reviewers.
      DATA SYNTHESIS: Traditionally, the problem of counterfeit pharmaceuticals has
      been limited to developing nations in Asia and Africa. Now, drug counterfeiting
      is rapidly becoming a worldwide concern, and counterfeit drugs are reaching the
      U.S. market. This article defines the problem of counterfeit drugs in its many
      forms and discusses the extent of the problem, with particular attention to the
      respective rates of counterfeiting across the globe and the origins of
      counterfeit drugs. CONCLUSION: Technologic advances have worsened the counterfeit
      drug problem. Because drug counterfeiting is a worldwide concern, worldwide
      action is needed to combat the problem.

PMID- 14717270
TI  - Reliability of saliva hormone tests.

PMID- 14717271
TI  - Intranasal flu vaccine available this season.
AB  - FluMist provides a convenient alternative to the traditional flu shot. Use of a
      live attenuated virus that stimulates an immune response directly in the nasal
      passages has certain therapeutic advantages in some patients. However, the cost
      of this form of flu vaccine is likely to be borne entirely by the patient.

PMID- 14717272
TI  - John Michael Maisch (1831-1893): father of adequate pharmaceutical legislation.

PMID- 14717274
TI  - Other people's money.

PMID- 14717273
TI  - Guidelines for provider-patient e-mail.

PMID- 14717275
TI  - More democracy in the House.

PMID- 14717276
TI  - Is testimony part of optometric/medical practice?

PMID- 14717277
TI  - Atypical presentation and review of the ICE syndrome.
AB  - BACKGROUND: The different variants of the iridocorneal endothelial (ICE) syndrome
      were separately described in the early to mid-1900's and were eventually linked
      to a common etiology of an abnormal corneal endothelium. The ICE syndrome
      typically manifests in early to middle adulthood, usually occurs in women, and is
      almost always unilateral. Management of patients with any variant of the ICE
      syndrome challenges even the best clinicians. CASE REPORT: We present a 52-year
      old patient with Chandler's syndrome. Our patient shared many of the classic
      characteristics of Chandler's syndrome, including peripheral anterior synechiae
      and corneal edema, with one unusual aspect--the patient was male. Details
      regarding the subsets of the ICE syndrome, differential diagnosis, and current
      understanding of the pathophysiology are also reviewed. CONCLUSION: The ICE
      syndrome is a progressive anterior segment disease that is quite difficult to
      manage. Corneal edema, increased IOP, and glaucoma are all sequelae of these
      conditions and, even in the best hands, are extremely challenging to manage.
      Today, nearly 100 years after Harms described the first patient with an ICE
      syndrome, we still do not know the exact mechanism for the corneal endothelial
      changes. Many investigations have been made into the causative agent or stimulus
      for abnormal endothelial growth in the ICE syndrome. No definitive proof has been
      established, but a relationship may exist with the Herpes Simplex and Epstein
      Barr viruses. Further investigation is needed to determine the most-appropriate
      treatment and management of the ICE syndrome.

PMID- 14717278
TI  - Correspondence of Tono-Pen intraocular pressure measurements performed at the
      central cornea and mid-peripheral cornea.
AB  - BACKGROUND: As the awareness of the influence of central corneal thickness (CCT)
      on Goldmann tonometry has increased, many publications have questioned the
      accuracy of Goldmann intraocular pressure (IOP) measurement. The Tono-Pen,
      because it indents a much smaller surface area when compared to a Goldmann probe,
      may be less affected by corneal thickness variations when compared with Goldmann
      tonometry. METHODS: Forty human subjects with no history of refractive surgery
      participated in this study. The IOP of the right eye of each subject was measured
      with the Goldmann tonometer, the Tono-Pen at the central cornea, and the Tono-Pen
      at the mid-peripheral cornea. An ultrasonic DGH Pachette pachymeter was used to
      measure the central and mid-peripheral corneal thickness at the location of the
      IOP readings. RESULTS: Tono-Pen measurements at the central and mid-peripheral
      cornea highly correlated (r = 0.933), and did not significantly differ (p =
      0.646). The IOP readings with the Goldmann tonometer (r= 0.406), the Tono-Pen at
      the central cornea (r = 0.453), and the Tono-Pen at the mid-peripheral cornea (r
      = 0.321) showed a positive correlation to corneal thickness. The Goldmann and
      Tono-Pen tonometers differed significantly in the measurement of IOP at the
      central cornea (p = 0.007), but were positively correlated (r = 0.674).
      CONCLUSIONS: The Tono-Pen IOP measurement at the central cornea highly
      approximated Tono-Pen IOP measurement at the mid-peripheral cornea. Furthermore,
      although not highly correlated, both the Goldmann and Tono-Pen tonometers showed
      a significantly positive correlation between IOP and corneal thickness
      measurements.

PMID- 14717279
TI  - Productivity associated with visual status of computer users.
AB  - BACKGROUND: The aim of this project is to examine the potential connection
      between the astigmatic refractive corrections of subjects using computers and
      their productivity and comfort. We hypothesize that improving the visual status
      of subjects using computers results in greater productivity, as well as improved
      visual comfort. METHODS: Inclusion criteria required subjects 19 to 30 years of
      age with complete vision examinations before being enrolled. Using a double
      masked, placebo-controlled, randomized design, subjects completed three
      experimental tasks calculated to assess the effects of refractive error on
      productivity (time to completion and the number of errors) at a computer. The
      tasks resembled those commonly undertaken by computer users and involved visual
      search tasks of: (1) counties and populations; (2) nonsense word search; and (3)
      a modified text-editing task. RESULTS: Estimates of productivity for time to
      completion varied from a minimum of 2.5% upwards to 28.7% with 2 D cylinder
      miscorrection. Assuming a conservative estimate of an overall 2.5% increase in
      productivity with appropriate astigmatic refractive correction, our data suggest
      a favorable cost-benefit ratio of at least 2.3 for the visual correction of an
      employee (total cost 268 dollars) with a salary of 25,000 dollars per year.
      CONCLUSIONS: We conclude that astigmatic refractive error affected both
      productivity and visual comfort under the conditions of this experiment. These
      data also suggest a favorable cost-benefit ratio for employers who provide
      computer-specific eyewear to their employees.

PMID- 14717280
TI  - Contact lens fitting over intrastromal corneal rings in a keratoconic patient.
AB  - BACKGROUND: Intrastromal corneal ring segments have been used as a refractive
      surgery method for treatment of myopia. More recently, attempts have been made to
      use this surgical procedure in patients with keratoconus. CASE REPORT: A 51-year
      old man with keratoconus came to the clinic for a contact lens refit. He had
      undergone surgical insertion of intrastromal corneal rings in his right eye 7
      months earlier in an attempt to obtain acceptable vision without contact lenses.
      At the time of presentation, the patient was not satisfied with his vision in the
      right eye and requested an attempt to improve his vision with a contact lens. The
      resulting corneal shape after surgery presented some complications, but the
      patient was able to achieve 20/25-vision and adequate comfort in his right eye
      with a piggyback contact lens system. CONCLUSIONS: Insertion of intrastromal
      corneal rings may be beneficial in patients with early keratoconus or who are
      contact lens-intolerant. However, patients with more-advanced keratoconus are not
      likely to achieve adequate vision after the surgery and will require a contact
      lens. In addition, changes in the corneal anatomy created by the intrastromal
      rings may make contact lens fitting more challenging. The corneal irregularity
      may be exacerbated due to drastic variations in corneal elevation over the
      intrastromal ring and directly adjacent to the ring. This irregularity in
      elevation leads to difficulty in centering the lens on the eye and problems with
      bubbles forming under the contact lens over areas of corneal depression. When
      successfully fitted, contact lenses over intrastromal corneal rings can improve
      vision significantly.

PMID- 14717281
TI  - Making the deal: a guide to successful negotiation.

PMID- 14717282
TI  - The 2003 AOA Economic Survey.

PMID- 14717283
TI  - CMS offers new answers to common HIPAA questions.

PMID- 14717284
TI  - Ice clouds and Asian dust studied with lidar measurements of particle extinction
      to-backscatter ratio, particle depolarization, and water-vapor mixing ratio over
      Tsukuba.
AB  - The tropospheric particle extinction-to-backscatter ratio, the depolarization
      ratio, and the water-vapor mixing ratio were measured by use of a Raman lidar and
      a polarization lidar during the Asian dust seasons in 2001 and 2002 in Tsukuba,
      Japan. The apparent (not corrected for multiple-scattering effects) extinction-to
      backscatter ratios (Sp) showed a dependence on the relative humidity with respect
      to ice (RHice) obtained from the lidar-derived water-vapor mixing ratio and
      radiosonde-derived temperature; they were mostly higher than 30 sr in dry air
      (RHice < 50%), whereas they were mostly lower than 30 sr in ice-supersaturated
      air (RHice > or = 100%), where the apparent extinction coefficients were larger
      than 0.036 km(-1). Both regions showed mean particle depolarization ratios of 20%
      22%. Comparisons with theoretical calculations and the previous experiments
      suggest that the observed dependence of Sp on RHice is attributed to the
      difference in the predominant particles: nonspherical aerosols (mainly the Asian
      dust) in dry air and cloud particles in ice-supersaturated air.

PMID- 14717285
TI  - Sonographic probing of laser filaments in air.
AB  - The acoustic wave emitted from the plasma channel associated with a filament
      induced by a femtosecond laser pulse in air was detected with a microphone. This
      sonographic detection provides a new method to determine the length and the
      spatial profile of the free-electron density of a filament. The acoustic wave is
      emitted owing to the expansion of the gas in the filament, which is heated
      through collisions with high-energy photoelectrons generated by multiphoton
      ionization. Compared with other methods, the acoustic detection is simpler, more
      sensitive, and with higher spatial resolution, making it suitable for field
      measurements over kilometer-range distances or laboratory-scale studies on the
      fine structure of a filament.

PMID- 14717286
TI  - Controlled core removal from a D-shaped optical fiber.
AB  - The partial removal of a section of the core from a continuous D-shaped optical
      fiber is presented. In the core removal process, selective chemical etching is
      used with hydrofluoric (HF) acid. A 25% HF acid solution removes the cladding
      material above the core, and a 5% HF acid solution removes the core. A red laser
      with a wavelength of 670 nm is transmitted through the optical fiber during the
      etching. The power transmitted through the optical fiber is correlated to the
      etch depth by scanning electron microscope imaging. The developed process
      provides a repeatable method to produce an optical fiber with a specific etch
      depth.

PMID- 14717287
TI  - Analysis of power-dependent phase-matched four-wave mixing in dispersion-managed
      transmission systems.
AB  - We investigate power-dependent phase-matched four-wave mixing (FWM) in wavelength
      division multiplexing transmission lines, in which positive and negative
      dispersion fibers are alternately arranged to manage the dispersion and the
      dispersion slope. The FWM effect shows power-independent phase matching when the
      channel power is low. However, it is power dependent at high power. The maximum
      FWM conversion efficiency is shifted away from the zero channel space in the case
      of power-dependent phase matching. Optimization of the dispersion system for
      suppression of the FWM effect is determined.

PMID- 14717288
TI  - Demonstration of a folded Sagnac sensor array immune to polarization-induced
      signal fading.
AB  - We demonstrate a new folded Sagnac sensor array design that combines a Faraday
      rotator mirror and a polarization beam splitter to eliminate the optical noise
      pulses otherwise generated in a folded Sagnac sensor array. A depolarization
      scheme compatible with this configuration is also proposed and demonstrated
      experimentally. It is shown that this new configuration passively eliminates
      polarization-induced signal fading on every sensor in the array. The minimum
      detectable phase was measured to be approximately 1.1 microrad/square root of Hz,
      in agreement with theory.

PMID- 14717289
TI  - Optical sensor based on Fabry-Perot resonance modes.
AB  - An oscillating wave sensor based on Fabry-Perot resonance modes has been
      developed. Different from the surface plasmon resonance sensors and the waveguide
      mode sensors in which the sample is located in the evanescent field region, the
      proposed device contains the sample in the core region that supports the
      oscillating field. Owing to the strong concentration of the electromagnetic field
      in the sensing medium, the proposed device exhibits unusual sensitivity
      enhancement, which has never been exploited in any other devices.

PMID- 14717290
TI  - Wavelength-flattened directional couplers: a geometrical approach.
AB  - A new approach to design a wavelength-insensitive optical power splitter is
      presented. First, a coupled-mode theory is cast in operatorial form. This allows
      us to solve the equivalent of coupled differential equations as simple limits.
      The operators are then represented on a generalized Poincare sphere, and the
      resulting graphical tool is applied to different structures, giving a clear
      interpretation of previous results in literature as well as hints on how to find
      improved solutions.

PMID- 14717291
TI  - Intensity and phase mapping of guided light in LiNbO3 waveguides with an
      interferometric near-field scanning optical microscope.
AB  - The design and implementation of a phase-sensitive near-field scanning optical
      microscope incorporating both heterodyne interferometric detection and a phase
      feedback mechanism are described. Using this microscope we demonstrate a new
      method for measuring the effective index of the guided mode of a waveguide from
      the phase images. Two types of LiNbO3 waveguide, defined by titanium diffusion or
      annealed proton exchange, were studied. Both the profile and the effective index
      of the mode were measured experimentally. For titanium-diffused waveguides, both
      agree well with values determined from numerical simulation. In annealed proton
      exchanged waveguides that contain periodically poled domains, we find evidence
      for backreflection from the boundaries between neighboring regions of opposite
      pole directions, which could result in transmission loss in this type of
      waveguide.

PMID- 14717292
TI  - Fluorescence losses from Yb:YAG slab lasers.
AB  - We report on the distribution of fluorescence that can be emitted through the
      surfaces of a ytterbium-doped yttrium aluminum garnet (Yb:YAG) slab-shaped high
      power solid-state laser. Slab shapes considered include parallel or antiparallel
      Brewster endfaced slabs and rectangular parallelepiped slabs. We treat cases in
      which all the faces of these slabs are in air, or with water or another coating
      on the largest faces. The fraction of the fluorescence emitted through each face,
      its distribution over that face, and the directions in which it travels are shown
      to be important to the design of high-power slab lasers.

PMID- 14717293
TI  - Efficient frequency doubling by a phase-compensated crystal in a semimonolithic
      cavity.
AB  - In multiple-pass nonlinear frequency conversion devices, interacting waves may
      accumulate different phases, owing to dispersive elements in the system. Phase
      compensation is therefore necessary for efficient frequency conversion. We
      experimentally demonstrate phase compensation in a compact semimonolithic
      frequency-doubling cavity by using a periodically poled KTP crystal. The
      conversion efficiency of the crystal was found to decrease at high pump powers,
      owing to power-dependent thermal lensing. This experimental observation was
      supported by a theoretical calculation of the conversion efficiency in a cavity,
      considering the mismatch between the mode's thermally loaded and unloaded
      cavities. A design procedure was also presented to compensate for the thermal
      lensing effect. The highest conversion efficiency of 56.5%, corresponding to a
      second-harmonic power of 117.5 mW at 532 nm, was achieved with a cw Nd:YAG pump
      power of 208 mW.

PMID- 14717294
TI  - Photoinduced birefringence of azodye-doped materials by a femtosecond laser.
AB  - Birefringence in azodye-doped polymethylmethacrylate and azodye-doped silica
      hybrid materials was induced by the two-photon excitation of a femtosecond laser.
      The growth and the relaxation characteristics of the photoinduced birefringence
      in the two types of material were investigated, and the probe transmittance for
      the induced birefringence was estimated to be 92%. Furthermore, an optical image
      storage based on this photoinduced birefringence was demonstrated.

PMID- 14717295
TI  - Reflow technique for the fabrication of an elliptical microlens array in sol-gel
      material.
AB  - A simple reflow technique is employed for the fabrication of elliptical
      refractive microlens arrays (MLAs) on a low-cost inorganic-organic SiO2/ZrO2 sol
      gel glass. The measured results show that the fabricated elliptical microlenses
      in a 256 x 512 array have excellent surface and dimensional qualities in terms of
      smoothness and uniformity. It is also shown that the optical parameters of the
      MLAs, such as the focal length and aperture dimension, can be accurately
      controlled. The proposed technique requires only an ordinary binary photomask for
      pattern transfer. Furthermore, the sol-gel material is found to be feasible for
      high-volume production, because the fabrication of MLAs can be implemented by use
      of cheap sol-gel materials without an etching step.

PMID- 14717296
TI  - Velocity matching of a GaAs electro-optic modulator.
AB  - New designs for the velocity matching of a deep-etched semiconductor electro
      optic modulator are presented. A tantalum pentoxide (Ta2O5) coating is considered
      here for achieving velocity matching between the microwave and the optical
      signals. The effects of the velocity mismatch, the conductor loss, the dielectric
      loss, and the impedance mismatch are studied in relation to the optical bandwidth
      of a high-speed semiconductor modulator. It is shown that both the dielectric
      loss and the impedance matching play key roles for velocity-matched high-speed
      modulators with low conductor loss. The effects of Ta2O5 thickness on the overall
      bandwidth and on the half-wave voltage-length product VpiL are also reported.

PMID- 14717297
TI  - La3Ga5SiQ14 single-crystal Q switch used as an electro-optic device.
AB  - A new kind of electro-optic Q switch is designed by use of a La3Ga5SiQ14 (LGS)
      crystal. Because the LGS crystal is optically active, the Q switch is based on
      the consideration that the total rotation angle of the polarization plane is
      zero, whereas the polarized wave propagates through the Pockels cell back and
      forth, with the polarization plane gyration and electro-optic effect existing
      simultaneously. The LGS Q switch is a practical electro-optic device that can be
      used in medium output energy lasers to partially take the place of deuterated
      potassium dihydrogen phosphate and lithium niobate Q switches.

PMID- 14717298
TI  - Timing modulation of a 40-MHz laser-pulse train for target ranging and
      identification.
AB  - We have demonstrated a target ranging and identification technique based on the
      timing modulation of a mode-locked laser coupled with fast incoherent detection.
      The range-to-target and the target-depth information have been determined with a
      resolution of better than 25 cm at single-pulse signal-to-noise ratios below 0.1.
      Our modeling results suggest that laser average power requirements remain a
      challenge, with upwards of 100 W likely needed for extension of this technique to
      ranges over 10 km, but improvements in overall system throughput would allow
      realization of its potential.

PMID- 14717299
TI  - Validation of satellite-retrieved oceanic inherent optical properties: proposed
      two-color elastic backscatter lidar and retrieval theory.
AB  - Recent radiative transfer models show that: (1) regardless of elastic lidar
      receiver field of view (FOV), at vanishing lidar depth the lidar-derived
      attenuation coefficient klidar --> a, where a is the total absorption coefficient
      per meter of depth; and (2) for a wide FOV as the lidar sensing depth approaches
      some large value (depending on water type), klidar --> Kd, where Kd is the
      diffuse attenuation for downwelling irradiance. As a result, it is shown that a
      time-resolved, dual-wavelength-laser, elastic-backscattering lidar can retrieve
      the three principal oceanic optical properties: (1) the absorption coefficient of
      phytoplankton aph, (2) the absorption coefficient of chromophoric dissolved
      organic matter (CDOM) aCDOM, and (3) the nonwater total constituent
      backscattering coefficient bbt. The lidar-retrieved aph, aCDOM, and bbt inherent
      optical properties can be used to validate corresponding satellite-derived
      products such as those from terra moderate-resolution imaging spectroradiometer
      (MODIS), Aqua MODIS, Sea-viewing Wide Field-of-view Sensor, (SeaWiFS), and other
      ocean color sensors.

PMID- 14717300
TI  - Remote sensing of cirrus cloud optical thickness and effective particle size for
      the National Polar-orbiting Operational Environmental Satellite System
      Visible/Infrared Imager Radiometer Suite: sensitivity to instrument noise and
      uncertainties in environmental parameters.
AB  - We describe sensitivity studies on the remote sensing of cirrus cloud optical
      thickness and effective particle size using the National Polar-orbiting
      Operational Environmental Satellite System Visible/Infrared Imager Radiometer
      Suite 0.67-, 1.24-, 1.61-, and 2.25-microm reflectances and thermal IR 3.70- and
      10.76-microm radiances. To investigate the accuracy and precision of the solar
      and IR retrieval methods subject to instrument noise and uncertainties in
      environmental parameters, we carried out signal-to-noise ratio tests as well as
      the error budget study, where we used the University of California at Los Angeles
      line-by-line equivalent radiative transfer model to generate radiance tables for
      synthetic retrievals. The methodology and results of these error analyses are
      discussed.

PMID- 14717301
TI  - Near-end solution for lidar signals that includes a multiple-scattering
      component.
AB  - A variant of the near-end solution is presented that allows one to consider a
      multiple-scattering component in lidar measurements of distant clouds or dense
      smoke. It is assumed that the lidar signal, contaminated by multiple scattering,
      obeys a single-scattering lidar equation in which an additional term, which is
      related to the range-dependent ratio of a multiple-to-single-scattering
      component, is included. For the inversion, a brink solution is proposed that does
      not require an a priori selection of the extinction-to-backscatter ratio in the
      optically dense aerosol formation under investigation. The solution requires
      either knowledge of the multiple-to-single-scattering ratio (e.g., determined
      experimentally with a multiangle lidar) or the use of the analytical dependence
      of the multiple-to-single-scattering ratio on the aerosol optical depth. In the
      latter case, an iterative technique is used.

PMID- 14717302
TI  - Mueller matrix imaging of targets in turbid media: effect of the volume
      scattering function.
AB  - Detecting objects in turbid media by use of just radiance signals has been a
      subject of study for many years. The use of Mueller matrix imaging methods has
      only recently been used as a tool for target detection. We will show not only
      that can targets still be detected by Mueller matrix methods even after their
      detection has escaped normal radiance schemes but also that their surface
      features can also still be distinguished. We will also show how the shape of the
      volume scattering function as well as the target and medium albedo strongly
      influences various elements of the Mueller matrix. One of the more interesting
      features of Mueller matrix imaging is that the diagonal elements are sensitive to
      perturbations in the environment surrounding the target. This implies that
      targets can be detected far beyond their geometric cross section. The methods
      presented here will have applications to submersible object detection, remote
      sensing in the atmosphere, and the detection of inhomogeneities in tissue.

PMID- 14717303
TI  - Amplified spontaneous emission in a Ti:sapphire regenerative amplifier.
AB  - Amplified spontaneous emission power and contrast ratio in a linear miltipass
      Ti:sapphire regenerative amplifier with a wavelength centered at 1054 nm are
      calculated and measured. It is shown that the passive losses of a seed pulse and
      the losses in coupling to the regenerative amplifier cavity mode degrade the
      intensity contrast ratio to 10(-6)-10(-7). The advantage of an optical parametric
      chirped pulse amplifier with respect to the contrast ratio is discussed.

PMID- 14717304
TI  - Wavelength dependence and figures of merit of ultrafast third-order optical
      nonlinearity of a conjugated 3,3'-bipyridine derivative.
AB  - The wavelength dependence and figures of merit of the third-order optical
      nonlinearity of a conjugated 3,3'-bipyridine derivative, a designed nondipolar
      structure of the donor-acceptor-acceptor-donor type, are reported. Z scans reveal
      positive nonlinear refractive-index changes for wavelengths longer than the one
      photon absorption wavelength. Although the value of nonlinear Kerr coefficient n2
      decreases from 6.0(+/- 0.2) x 10(-6) cm2/GW at 750 nm to 4.6(+/- 0.7) x 10(-6)
      cm2/GW at 1550 nm, the value of nonlinear absorption beta decreases from 0.084
      cm/GW at 750 nm to a negligible value at 1550 nm, giving rise to excellent
      nonlinearity-to-loss figures of merit at telecommunications wavelengths.

PMID- 14717305
TI  - Births: final data for 2002.
AB  - OBJECTIVES: This report presents 2002 data on U.S. births according to a wide
      variety of characteristics. Data are presented for maternal demographic
      characteristics including age, live-birth order, race, Hispanic origin, marital
      status, and educational attainment; maternal characteristics (medical risk
      factors, weight gain, tobacco, and alcohol use); medical care utilization by
      pregnant women (prenatal care, obstetric procedures, complications of labor
      and/or delivery, attendant at birth, and method of delivery); and infant
      characteristics (period of gestation, birthweight, Apgar score, abnormal
      conditions, congenital anomalies, and multiple births). Also presented are birth
      and fertility rates by age, live-birth order, race, Hispanic origin, and marital
      status. Selected data by mother's State of residence are shown, as well as data
      on month and day of birth, sex ratio, and age of father. Trends in fertility
      patterns and maternal and infant characteristics are described and interpreted.
      METHODS: Descriptive tabulations of data reported on the birth certificates of
      the 4.022 million births that occurred in 2002 are presented. Denominators for
      population-based rates are derived from the 2000 U.S. census. Rates for 1991-2001
      may differ from those published previously based on the 1990 U.S. census.
      RESULTS: There were 4,021,726 live births in 2002, essentially unchanged from
      2001. The birth rate, fertility rate, and total fertility rates all declined 1
      percent in 2002. The teenage birth rate dropped 5 percent, reaching another
      record low. The birth rates for women 20-24 years declined, whereas the rate for
      women 25-29 years was stable. The birth rate for women 30-34 years declined, but
      the rate for women 35-44 years continued to rise. Births to unmarried women
      changed very little. Smoking during pregnancy was down again. The timeliness of
      prenatal care continued to improve. The cesarean delivery rate climbed to the
      highest level ever reported in the United States (26.1 percent) and the rate of
      vaginal birth after previous cesarean plummeted 23 percent to 12.6 percent.
      Preterm and low birthweight levels both rose for 2002. The twin birth rate
      continued to climb, but the rate of triplet/+ births was down slightly.

PMID- 14717306
TI  - David D. Davis's obstetric textbook and atlas.

PMID- 14717307
TI  - Should obstetricians support a 'term cephalic trial'?
AB  - Recent analyses of the published data suggest that the risks of elective
      Caesarean delivery in an uncomplicated pregnancy may not outweigh the benefits of
      vaginal birth by as much as has been supposed. Indeed, this balance may be so
      close that the place of elective Caesarean delivery of a term cephalic baby might
      be considered as a worthwhile subject of a randomised controlled trial. We
      discuss the potential consequences of such a trial and what effect it could have
      on obstetric practice.

PMID- 14717308
TI  - Hysteroscopy under general anaesthesia, a near painless procedure.
AB  - Anecdotally, hysteroscopy and curettage under general anaesthesia causes crampy
      postoperative pain. A randomised, double-blind trial to investigate whether
      intrauterine lignocaine could decrease such pain was initiated by us. At an
      interim analysis, the results of the study found that almost half of all women
      studied so far (n = 53) were completely painfree from the moment they awoke with
      no difference between placebo and treatment groups. Of the remainder, most rated
      pain as either 'mild', or less. For most women, hysteroscopy, dilatation and
      curettage causes either none or very little pain postoperatively.

PMID- 14717309
TI  - Implanon implant detection with ultrasound and magnetic resonance imaging.
AB  - OBJECTIVE: The objective of the present study was to determine the degree of
      difficulty in locating Implanon (Organon, Sydney, Australia) contraceptive rods
      which had been inserted suboptimally, using both ultrasound and magnetic
      resonance imaging (MRI). METHODS: Volunteers with correctly placed Implanon rods
      were recruited for normal scanning protocols. A phantom was used to display
      abnormal rod placements. Ultrasound imaging was carried out using a variety of
      transducers to demonstrate their suitability. An MRI scanning protocol was
      formulated to achieve required views in the shortest time. RESULTS: All Implanon
      rods were successfully imaged with both ultrasound and MRI. CONCLUSION: High
      resolution linear array transducers combined with the correct scanning protocol
      should enable visualisation of Implanon rods in almost all cases. The MRI imaging
      requires caution when differentiating blood vessels and fibrous septae from the
      Implanon rods.

PMID- 14717310
TI  - Study of knowledge of genital herpes infection and attitudes to testing for
      genital herpes among antenatal clinic attendees.
AB  - A descriptive survey of knowledge of genital herpes and attitudes to testing was
      conducted among antenatal clinic attendees at the Gold Coast Hospital, Australia.
      The study subjects showed a good knowledge of genital herpes, to a level that
      appears sufficient for an informed choice regarding herpes serology testing to be
      made. A preference for testing for genital herpes was suggested. Although
      serological testing is not routinely required, the results of the study indicate
      that discussion of genital herpes should be considered in the antenatal clinic
      setting.

PMID- 14717311
TI  - Women's choice in the gender and ethnicity of her obstetrician and gynaecologist.
AB  - OBJECTIVE: To ascertain women's preferences in the gender and ethnicity of her
      obstetrician or gynaecologist and to determine whether there were differences in
      preferences among different ethnic and age groups. STUDY DESIGN: A simple 11-item
      questionnaire was placed at the antenatal and gynaecological clinics provided by
      South Auckland Health. The questionnaire was voluntary and 848 women completed
      the questionnaire over a 4-month period. RESULTS: Half of the women preferred a
      woman doctor and the other half had no preference. There was a 6% increase in
      preference for a woman doctor where an examination was required. Of the women who
      preferred a female doctor, 45% would change their preference if a chaperone were
      present. There was no disproportionate increase in preference for a woman doctor
      by the patient's ethnicity or age group. Most of the women did not think the
      ethnicity of her doctor mattered; however, 18% preferred the ethnicity of her
      doctor be similar to hers. There were more European women who preferred a
      European doctor and fewer Maori women would prefer a Maori doctor. Of the 9% of
      women who did not prefer a doctor of the same ethnicity to hers, Pacific Island
      women were over-represented. CONCLUSION: This is the first study of this nature
      in New Zealand and the findings on preference for a female doctor are similar to
      those from other countries. The results of the present study did not show any
      difference in preference by women from the ethnicities studied and by age group.
      The use of a chaperone where a male doctor suggests an examination will reassure
      nearly half of those women who preferred a female doctor. Although most women did
      not think the ethnicity of her doctor mattered, there were distinct differences
      by ethnicity with more European women preferring a European doctor and fewer
      Maori women preferring a Maori doctor. A qualitative study is needed to ascertain
      reasons for these differences in preference.

PMID- 14717312
TI  - Betamethasone associated changes in umbilical artery flow velocity waveforms in
      multiple pregnancies with umbilical artery absent end diastolic flow.
AB  - OBJECTIVES: It has been previously shown that glucocorticoids alter umbilical
      artery flow velocity waveforms in singleton pregnancies complicated by umbilical
      artery absent end diastolic flow. Whether similar effects are evident in multiple
      pregnancies where one fetus has umbilical artery absent end diastolic flow is not
      known. METHODS: Women with a twin or triplet pregnancy complicated by umbilical
      artery absent end diastolic flow in one fetus were admitted to hospital for
      intensive fetal surveillance including daily umbilical artery flow velocity
      waveform studies, as per hospital protocol. All women received prophylactic
      betamethasone (11.4 mg x 2, 24 h apart) in anticipation of preterm delivery.
      RESULTS: Between October 1996 and February 2002, 24 women with a multiple
      pregnancy complicated by umbilical artery absent end diastolic flow were cared
      for. Of these, six had a pregnancy with feto-fetal transfusion and excluded from
      further analysis. Of the remaining 18 women, eight had monochorionic diamniotic
      twins, eight had dichorionic twins, and two had trichorionic, triamniotic
      triplets. The median (range) gestation at diagnosis of umbilical artery absent
      end diastolic flow was 210.5 days (173-241). In nine (50%) of the 18 pregnancies
      the administration of betamethasone was associated with return of umbilical
      artery end diastolic flow for a median of 5 days. There was no association
      between this effect and chorionicity. The median (range) interval from diagnosis
      of umbilical artery absent end diastolic flow to delivery was 11 days (1-46).
      CONCLUSIONS: As previously reported in singleton pregnancies, the maternal
      administration of betamethasone in multiple pregnancies with umbilical artery
      absent end diastolic flow is associated with a transient return of end diastolic
      flow.

PMID- 14717313
TI  - Role of fertility treatments in multiple pregnancy at National Women's Hospital
      from 1996 to 2001.
AB  - OBJECTIVE: To determine the influence of fertility treatments on multiple
      pregnancy rates. STUDY DESIGN: A retrospective audit of women with multiple
      pregnancies from 1996 to 2001 at National Women's Hospital (NWH), Auckland, New
      Zealand was conducted. Information was collected regarding the demographics,
      fertility treatment, outcome of the pregnancy and complications experienced by
      women discharged with multiple births as an discharge diagnosis. RESULTS: For the
      years 1996-2001 there were 1136 multiple births at NWH. Of these births, 201
      (18%) were conceived following fertility treatment. Seventeen percent of twin
      births and 44% of triplet births were conceived following fertility treatment.
      There was a statistically significant increase in the number of births conceived
      following fertility treatment, from 9%, in 1996 to 24%, in 2001, although the
      proportion of births that were multiple overall did not change (20% in 1996 and
      2.3%, in 2001). Sixty-three percent of all fertility conceived multiple births
      were following in vitro fertilization/intracytoplasmic sperm injection treatment.
      Sixty percent of these women had two embryos transferred and 31% had three
      embryos transferred. Ovulation induction with follicle-stimulating hormone
      accounted for 19% of all fertility conceived multiple births. Nineteen percent of
      fertility conceived multiple births followed clomiphene treatment alone.
      CONCLUSIONS: The proportion of multiple pregnancies as a result of fertility
      treatments has increased over the 6 years studied.

PMID- 14717314
TI  - Replacement of one selected embryo is just as successful as two embryo transfer,
      without the risk of twin pregnancy.
AB  - The transition of in vitro fertilization from research to standard clinical
      practice has, to a great extent, been as a result of the use of controlled
      ovarian hyper stimulation. A disadvantage of the availability of multiple embryos
      has been the replacement of several embryos leading to an epidemic of multiple
      pregnancies. This retrospective review of 2606 fresh embryo transfers between
      2001 and 2003, where either one or two selected embryos were replaced from an
      available cohort of at least four, shows that single embryo transfers have a
      similar pregnancy rate without the risk of multiple pregnancy.

PMID- 14717315
TI  - Impact of intrapartum epidural analgesia on breast-feeding duration.
AB  - BACKGROUND: Although the labour and delivery outcomes of epidural analgesia have
      been investigated extensively, the effects on breast-feeding success are not
      clearly identified. AIM: To investigate the effects of intrapartum epidural
      analgesia on breast-feeding duration. METHODS: Nulliparous women enrolled in a
      randomised trial investigating labour and delivery outcomes of intrapartum
      epidural analgesia were asked about breast-feeding outcomes. Breast-feeding
      duration was ascertained by a self-report at 2 and 6 months post-partum. Breast
      feeding outcomes were analysed as a prospective observational study because of
      high cross-over rates (43.4%) in the original randomised controlled trial.
      RESULTS: A total of 992 women were recruited to the trial with 690 (69.6%)
      receiving epidural analgesia in labour. Breast-feeding was initiated by 95% (n =
      946). At 2 and 6 months, 625 (63.5%) and 401 (40.7%), respectively, were still
      breast-feeding. Intrapartum analgesia (trend P-value = 0.036), mode of delivery
      (P < 0.001), age (P < 0.001), education (P < 0.001), and smoking in pregnancy (P
      < 0.001) showed univariate associations with breast-feeding duration. In the
      subgroup of women with spontaneous onset of labour and vaginal deliveries, after
      controlling for other obstetric and demographic factors, epidural analgesia but
      not narcotic analgesia was significantly associated with reduced breast-feeding
      duration (adjusted hazard ratio 1.44, 95% confidence interval 1.04-1.99).
      CONCLUSIONS: Nulliparous women have a high use of epidural analgesia in labour.
      Nulliparous women who choose epidural analgesia are more likely to breast-feed
      for shorter durations. Further exploration of the factors underlying this
      association should be undertaken.

PMID- 14717316
TI  - Ultrasound detection of the Essure permanent birth control device: a case series.
AB  - BACKGROUND: The current recommendation to check the position of the Essure
      permanent birth control (PBC) micro-insert device after its insertion is by
      abdominal X-ray 3 months after insertion. We propose that ultrasound imaging is
      more suited for this purpose and gives reassurance much earlier. The sonographic
      appearance of the micro-inserts and the reliability of this modality in
      localising the devices is described in the present study. OBJECTIVE: To ascertain
      the appearance of the Essure PBC device at transvaginal and transabdominal
      ultrasound scanning and to determine the reliability of this approach in
      localising the contraceptive device. STUDY POPULATION AND METHODS: All patients
      who had the Essure PBC procedure between June 2002 and January 2003 at our centre
      were offered an ultrasound scan to check device position. RESULTS: The micro
      inserts were easily distinguished by their echogenic coil-like appearance within
      each uterine cornua extending into the proximal fallopian tube. Of the 15
      patients examined, 14 pairs of devices were seen: one device was malpositioned in
      the lower part of the uterus. In one patient, only one device was seen in the
      correct position but the other device was not identified and presumably expelled
      after a notably difficult insertion. DISCUSSION: Ultrasound appears to be well
      suited for micro-insert localisation. An early post insertion ultrasound scan is
      recommended to reassure about correct positioning of device and may potentially
      alleviate patient anxiety, or diagnose malposition early.

PMID- 14717317
TI  - Transverse upper vaginal septum presenting in pregnancy: a case report and review
      of the literature.

PMID- 14717318
TI  - Complex long-term eating disorder, Bartter's syndrome and pregnancy: a rare
      combination.

PMID- 14717319
TI  - Naltrexone implant and blood naltrexone levels over pregnancy.

PMID- 14717320
TI  - Vulvovaginal-gingival syndrome of lichen planus: diagnostic and therapeutic
      challenge.

PMID- 14717321
TI  - Intravesical migration of an intrauterine device with stone formation.

PMID- 14717322
TI  - Malignant gestational trophoblastic disease presenting as extradural mass.

PMID- 14717323
TI  - Re: Twenty-three years of labour floor records, Vila Central Hospital, Vanuatu.

PMID- 14717324
TI  - The use of the ventouse at Caesarean section.

PMID- 14717325
TI  - Comment: Anatomy of complications workshop: an educational strategy to improve
      performance in obstetricians and gynaecologists.

PMID- 14717326
TI  - Re: Massive vulvar edema in pregnancy.

PMID- 14717327
TI  - The management of twin births in Australia and New Zealand.

PMID- 14717328
TI  - Mouse reporter strain for noninvasive bioluminescent imaging of cells that have
      undergone Cre-mediated recombination.
AB  - Conditional alleles containing LoxP recombination sites, in conjunction with Cre
      recombinase delivered by a variety of means, allows for spatial and temporal
      control of gene expression in mouse models. Here we describe a mouse strain in
      which a luciferase (Luc) cDNA, preceded by a LoxP-stop-LoxP (L-S-L) cassette, was
      introduced into the ubiquitously expressed ROSA26 locus. Mouse embryo fibroblasts
      derived from this strain expressed luciferase after Cre-mediated recombination in
      vitro. ROSA26 L-S-L-Luc/+ mice expressed luciferase in a diffuse or liver
      restricted pattern, as determined by noninvasive, bioluminescent imaging, when
      crossed to transgenic mice in which Cre was under the control of a zygotically
      expressed (EIIA-Cre), or a liver-restricted (albumin-Cre), promoter,
      respectively. Organ-specific luciferase expression was also seen after
      intraparenchymal administration of an adenovirus encoding Cre. The ROSA26 L-S-L
      Luc/+ strain should be useful for characterizing Cre mouse strains and for
      following the fate of cells that have undergone Cre-mediated recombination in
      vivo.

PMID- 14717329
TI  - Current advances in molecular imaging: noninvasive in vivo bioluminescent and
      fluorescent optical imaging in cancer research.
AB  - Recently, there has been tremendous interest in developing techniques such as
      MRI, micro-CT, micro-PET, and SPECT to image function and processes in small
      animals. These technologies offer deep tissue penetration and high spatial
      resolution, but compared with noninvasive small animal optical imaging, these
      techniques are very costly and time consuming to implement. Optical imaging is
      cost-effective, rapid, easy to use, and can be readily applied to studying
      disease processes and biology in vivo. In vivo optical imaging is the result of a
      coalescence of technologies from chemistry, physics, and biology. The development
      of highly sensitive light detection systems has allowed biologists to use imaging
      in studying physiological processes. Over the last few decades, biochemists have
      also worked to isolate and further develop optical reporters such as GFP,
      luciferase, and cyanine dyes. This article reviews the common types of
      fluorescent and bioluminescent optical imaging, the typical system platforms and
      configurations, and the applications in the investigation of cancer biology.

PMID- 14717330
TI  - Breaching biological barriers: protein translocation domains as tools for
      molecular imaging and therapy.
AB  - The lipid bilayer of a cell presents a significant barrier for the delivery of
      many molecular imaging reagents into cells at target sites in the body. Protein
      translocation domains (PTDs) are peptides that breach this barrier. Conjugation
      of PTDs to imaging agents can be utilized to facilitate the delivery of these
      agents through the cell wall, and in some cases, into the cell nucleus, and have
      potential for in vitro and in vivo applications. PTD imaging conjugates have
      included small molecules, peptides, proteins, DNA, metal chelates, and magnetic
      nanoparticles. The full potential of the use of PTDs in novel in vivo molecular
      probes is currently under investigation. Cells have been labeled in culture using
      magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess
      trafficking patterns relative to cells expressing a target antigen. In vivo
      imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated
      in living animals. Here we review several natural and synthetic PTDs that have
      evolved in the quest for easier translocation across biological barriers and the
      application of these peptide domains to in vivo delivery of imaging agents.

PMID- 14717331
TI  - A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging
      using MRI.
AB  - A novel polyacrylamide superparamagnetic iron oxide nanoparticle platform is
      described which has been synthetically prepared such that multiple crystals of
      iron oxide are encapsulated within a single polyacrylamide matrix (PolyAcrylamide
      Magnetic [PAM] nanoparticles). This formulation provides for an extremely large
      T2 and T2* relaxivity of between 620 and 1140 sec(-1) mM(-1). Administration of
      PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative
      pharmacokinetic analysis of the uptake of nanoparticles in the vasculature,
      brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and
      10 kDa) to the surface of the PAM nanoparticles resulted in an increase in plasma
      half-life and affected tumor uptake and retention of the nanoparticles as
      quantified by changes in tissue contrast using MRI. The flexible formulation of
      these nanoparticles suggests that future modifications could be accomplished
      allowing for their use as a targeted molecular imaging contrast agent and/or
      therapeutic platform for multiple indications.

PMID- 14717332
TI  - Synthesis and characterization of a Gd-DOTA-D-permeation peptide for magnetic
      resonance relaxation enhancement of intracellular targets.
AB  - Many MR contrast agents have been developed and proven effective for
      extracellular nontargeted applications, but exploitation of intracellular MR
      contrast agents has been elusive due to the permeability barrier of the plasma
      membrane. Peptide transduction domains can circumvent this permeability barrier
      and deliver cargo molecules to the cell interior. Based upon enhanced cellular
      uptake of permeation peptides with D-amino acid residues, an all-D Tat basic
      domain peptide was conjugated to DOTA and chelated to gadolinium. Gd-DOTA-D-Tat
      peptide in serum at room temperature showed a relaxivity of 7.94 +/- 0.11 mM(-1)
      sec(-1) at 4.7 T. The peptide complex displayed no significant binding to serum
      proteins, was efficiently internalized by human Jurkat leukemia cells resulting
      in intracellular T1 relaxation enhancement, and in preliminary T1-weighted MRI
      experiments, significantly enhanced liver, kidney, and mesenteric signals.

PMID- 14717333
TI  - Repetitive imaging of reporter gene expression in the lung.
AB  - Positron emission tomographic imaging is emerging as a powerful technology to
      monitor reporter transgene expression in the lungs and other organs. However,
      little information is available about its usefulness for studying gene expression
      over time. Therefore, we infected 20 rats with a replication-deficient adenovirus
      containing a fusion gene encoding for a mutant Herpes simplex virus type-1
      thymidine kinase and an enhanced green fluorescent protein. Five additional rats
      were infected with a control virus. Pulmonary gene transfer was performed via
      intratracheal administration of vector using a surfactant-based method. Imaging
      was performed 4-6 hr, and 4, 7, and 10 days after gene transfer, using 9-(4-[18F]
      fluoro-3-hydroxymethylbutyl)guanine, an imaging substrate for the mutant kinase.
      Lung tracer uptake assessed with imaging was moderately but significantly
      increased 4-6 hr after gene transfer, was maximal after 4 days, and was no longer
      detectable by 10 days. The temporal pattern of transgene expression measured ex
      vivo with in vitro assays of thymidine kinase activity and green fluorescent
      protein was similar to imaging. In conclusion, positron emission tomography is a
      reliable new tool to evaluate the onset and duration of reporter gene expression
      noninvasively in the lungs of intact animals.

PMID- 14717334
TI  - Miniaturized multichannel near infrared endoscope for mouse imaging.
AB  - We describe the design and construction of a miniaturized multichannel near
      infrared (NIR) endoscopic imaging system developed for high-resolution imaging of
      mice. The device allows for simultaneous real-time video images in white light
      and two independent NIR channels. Testing demonstrated independent acquisition of
      nanomolar concentrations of fluorochromes Cy5.5 and Cy7. Cross-talk between the
      NIR channels, partially a result of broad tails in the spectra of commonly used
      organic fluorochromes, was assessed, modeled for the linear range of the
      concentration/signal intensity function, and compensated. The calculated
      compensation was 5.5% and 22% of the total signal intensity in the two channels
      NIR700 and NIR780, respectively, at equal concentrations of the two
      fluorochromes. Using a mouse model of colonic adenomatosis, we show that both
      perfusion and protease activity can be detected simultaneously, independently,
      and repeatedly in live mice. The developed device should be useful for in vivo
      imaging of diverse molecular targets.

PMID- 14717335
TI  - Molecular analysis of the structure and function of the angiotensin II type 1
      receptor.
AB  - The renin-angiotensin system hormone angiotensin II (Ang II) plays a central role
      in the pathophysiology of hypertension, cardiac hypertrophy, congestive heart
      failure, and coronary heart disease. Two distinct subtypes of Ang II receptor,
      type 1 (AT1) and type 2 (AT2), have been identified, and both have been shown to
      belong to the G-protein-coupled receptor superfamily (GPCRs). The recent Human
      Genome Project has revealed more than 1,000 transmembrane (TM) receptors that
      belong to this superfamily, and it has been estimated that 50% of all clinically
      used medicines modulate GPCRs activity. Recently, there have been many new
      insights regarding Ang II receptors and other GPCRs, such as on homo- and hetero
      oligomerization, constitutive activation, movement of TM helices,
      internalization, desensitization and phosphorylation, trafficking, nuclear
      localization, intracellular protein-induced receptor activation, and receptor
      associated proteins. Although AT1 receptor antagonists which prevent Ang II
      induced signaling are already clinically available, we here summarize new
      findings regarding their structure and function, and the possibility of new
      therapeutic strategies for targeting Ang II receptors through molecular
      biological techniques.

PMID- 14717336
TI  - Carotid intima-media thickness is correlated with impairment of coronary flow
      reserve in hypertensive patients without coronary artery disease.
AB  - Hypertensive individuals occasionally experience angina-like chest pain despite
      having angiographically normal coronary arteries, and the etiology of this
      phenomenon has been suggested to be associated with depressed coronary flow
      reserve (CFR). Carotid intima-media thickness (IMT) assessed by ultrasound is
      correlated with not only cerebrovascular disease but also coronary artery disease
      and left ventricular hypertrophy (LVH). The aim of our study was to investigate
      the association between CFR and carotid IMT in patients with essential
      hypertension. We performed transthoracic Doppler recording of diastolic coronary
      flow velocity in the left anterior descending coronary artery at baseline and
      after maximal vasodilation by adenosine triphosphate infusion in 24 normotensive
      subjects and 125 hypertensive patients. CFR was defined as the ratio of hyperemic
      to basal averaged peak coronary flow velocity. Common cardiovascular risk
      factors, left ventricular mass index (LVMI), relative wall thickness (RWT), and
      carotid IMT were evaluated. The CFR of hypertensive patients (2.55 +/- 0.52) was
      significantly decreased compared with that of normotensive subjects (3.15 +/-
      0.45). CFR showed a significant correlation with age, systolic blood pressure,
      RWT, and carotid IMT. Stepwise regression analysis revealed that, among carotid
      IMT, LVMI and RWT, only carotid IMT was a strong and independent parameter for
      predicting CFR in hypertensive patients. In conclusion, B-mode ultrasound
      scanning of the carotid artery seemed to be of clinical value in the screening of
      patients with LVH and impaired microcoronary circulation. These associations may
      explain the links between cardiac and cerebrovascular involvements in patients
      with hypertension.

PMID- 14717337
TI  - Vitamin C improves attenuated angiotensin II-induced endothelium-dependent
      vasodilation in human forearm vessels.
AB  - Endothelial dysfunction might be related to an increase in superoxide anion
      production in patients with hypertension, hypercholesterolemia, diabetes
      mellitus, and heart failure. Studies in animal models indicate that angiotensin
      II increases superoxide anion production by vascular tissues. We examined whether
      angiotensin II attenuates endothelium-dependent vasodilation via an increase in
      superoxide anion production in human forearm vessels in vivo. Forearm blood flow
      was measured in 23 healthy young men. We examined forearm vasodilator responses
      to an intra-arterial infusion of acetylcholine (4, 8, and 16 microg/min) and
      sodium nitroprusside (0.8, 1.6, and 3.2 microg/min) before and during an intra
      arterial infusion of anglotensin II (n=8), angiotensin II plus vitamin C (n=8),
      and vitamin C alone (n=4). Angiotensin II attenuated the forearm vasodilatory
      response to acetylcholine (p<0.05), and this attenuated response was abolished by
      vitamin C. Angiotensin II did not alter the forearm vasodilatory response to
      sodium nitroprusside, and vitamin C infusion did not affect the forearm
      vasodilatory response to either acetylcholine or sodium nitroprusside. The
      forearm vasodilator response to acetylcholine did not change during infusion of
      norepinephrine (n=3), which reduced forearm blood flow to a degree similar to
      that by angiotensin II infusion. These results suggest that angiotensin II
      attenuates endothelium-dependent forearm vasodilation, and vitamin C improves
      this impairment. Thus, angiotensin II likely attenuates endothelium-dependent
      vasodilation via an increase of superoxide anion production in the human forearm
      in vivo.

PMID- 14717338
TI  - Relation between blood pressure and rhinitis in a Japanese adolescent population.
AB  - Recent studies have reported an association between systolic blood pressure (BP)
      and rhinitis. The prevalence of allergic rhinitis is 20% to 30% in Japan. The
      present cross-sectional study was performed to assess the relation between BP and
      allergic rhinitis in a sample of 2,292 male adolescent high school students who
      attended the annual school health examination. Of the 2,292 students (mean age,
      16 years), 26.6% were considered to have allergic rhinitis based on their
      responses to a questionnaire, 25.1% were diagnosed with allergic rhinitis by an
      otolaryngologist, and 12.6% were consistently diagnosed with allergic rhinitis by
      both questionnaire and an otolaryngologist. There was no difference in systolic
      BP between subjects with and without allergic rhinitis. Diastolic BP, however,
      was higher in subjects without allergic rhinitis than in those with allergic
      rhinitis as diagnosed by questionnaire alone or by both questionnaire and an
      otolaryngologist. When the subjects were divided into three BP categories
      (normal, high normal, and hypertension) according to the criteria in the JSH
      2000, the rates of allergic rhinitis were similar in the three BP categories.
      These findings do not confirm a relation between allergic rhinitis and systolic
      BP.

PMID- 14717339
TI  - Effects of radiation on fatty liver and metabolic coronary risk factors among
      atomic bomb survivors in Nagasaki.
AB  - In order to clarify the basic mechanism(s) linking radiation exposure and
      coronary heart disease (CHD), we here collected ultrasonographic data on fatty
      liver and measured levels of metabolic CHD risk factors from November 1990
      through October 1992 in 1,517 Nagasaki atomic bomb survivors (575 men and 942
      women). Using a cross-sectional study design, we examined the effects of
      radiation dose on fatty liver and CHD risk factors by means of a multiple
      logistic regression model. Fatty liver was related to the metabolic CHD risk
      factors associated with insulin resistance syndrome: obesity, hypertension,
      hypercholesterolemia, low high density lipoprotein (HDL)-cholesterol,
      hypertriglyceridemia, and abnormal glucose metabolism. Radiation dose was
      positively related to fatty liver, low HDL-cholesterol, and hypertriglyceridemia,
      whereas it had no effects on obesity, hypertension, hypercholesterolemia, or
      abnormal glucose metabolism. The present results suggested that radiation dose
      was related to 1) fatty liver, which clustered the metabolic CHD risk factors
      associated with insulin resistance syndrome and 2) atherogenic lipid profiles. It
      is suggested that these associations are involved in the basic mechanism(s)
      linking radiation exposure and CHD.

PMID- 14717340
TI  - Association between left ventricular diastolic dysfunction and renal hemodynamic
      change in patients with treated essential hypertension.
AB  - The heart and kidneys are important target organs in hypertension. Early signs of
      hypertensive target organ damage can be detected by evaluating left ventricular
      (LV) diastolic function and intrarenal hemodynamics using Doppler
      ultrasonography. However, it has not been sufficiently clarified whether cardiac
      damage and renal impairment progress in parallel, especially from the early
      stage. In the present study, Doppler echocardiography and renal Doppler
      ultrasonography were performed in 99 patients with treated essential
      hypertension, and LV diastolic filling parameters, ie., the velocity ratio of
      atrial filling to early diastolic filling (A/E), and the deceleration time of the
      E wave (DcT) and renal Doppler parameters, i.e., the diastolic to systolic ratio
      (D/S) and resistance index (RI), were determined. D/S was negatively correlated
      and RI was positively correlated with A/E and DcT. These cardiac and renal
      Doppler parameters were also associated with age, diastolic blood pressure,
      creatinine clearance, and/or glucose levels. By multiple regression analysis, D/S
      was found to have a significant association with DcT, independent of other
      clinical parameters, including age. In subgroup analysis in which patients were
      divided by their glucose tolerance, a significant correlation between renal
      Doppler parameters and LV diastolic function was observed in subjects with normal
      glucose tolerance, but this correlation disappeared in those with impaired
      glucose tolerance and diabetes mellitus. The present findings show that there is
      a significant relation between LV diastolic function and renal Doppler parameters
      in treated hypertensive patients, and suggest that cardiac damage progresses in
      parallel with renal involvement in these patients from the early stage.

PMID- 14717341
TI  - Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of
      cardiovascular events in high-risk hypertensive patients: rationale, design, and
      methods.
AB  - Hypertension continues to be a major public health issue in the world. To combat
      this problem, many anti-hypertensive drugs have been developed and proven
      effective at controlling blood pressure in the last half century. In recent
      decades, antihypertensive drugs have been shown to have cardiovascular benefits
      beyond the reduction of blood pressure, and the focus has shifted to
      clarification of these effects. Angiotensin II receptor antagonists and calcium
      channel blockers are the most widely used antihypertensive drugs in Japan.
      However, these two classes of drugs have not yet been compared with respect to
      their efficacy for treating cardiovascular events. The Candesartan
      Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is
      a prospective, multicenter, randomized, open-label, active-controlled, 2-arm
      parallel group comparison with a response-dependent dose titration and blinded
      assessment of endpoints in high-risk hypertensive patients treated with either an
      angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation
      calcium channel blocker (amlodipine besilate). The eligibility criteria in this
      study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or
      = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70
      years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive
      measurements at clinic; and 3) at least one of the following high risk factors
      for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two
      consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126
      mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood
      glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current
      treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral
      infarction, or transient ischemic attack until 6 months prior to the screening,
      d) left ventricular hypertrophy on either echocardiography or ECG, angina
      pectoris, or history of myocardial infarction until 6 months prior to screening,
      e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of
      arteriosclerotic artery obstruction. The therapeutic goals of blood pressure
      control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below
      60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP <
      150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP <
      90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to
      each of the two treatment arms, were required based on a two-sided alpha level
      0.05 and 90% power. The CASE-J is also the first study to employ the newly
      developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding,
      Data Management (ABCD) system for data collection and management. Enrollment of
      patients started in September 2001 and ended in December 2002. Follow-up data
      will be collected every 6 months until December 2005. The CASE-J trial will
      provide important evidence on the comparative effectiveness of candesartan
      cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among
      Japanese. In addition, the use of the ABCD system is expected to contribute to
      the development of more efficient data management systems for large-scale
      clinical trials.

PMID- 14717342
TI  - Reduced endothelial vasomotor function and enhanced neointimal formation after
      vascular injury in a rat model of blood pressure lability.
AB  - Increased short-term blood pressure variability is known to be associated with
      hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked
      increase in blood pressure lability without affecting the average blood pressure
      level. The aim of this study was to investigate the effects of blood pressure
      lability on endothelial vasomotor function and neointimal formation after balloon
      injury in SAD rats. Direct longterm measurement of mean arterial pressure showed
      no significant difference in the average of mean arterial pressure between the
      SAD group and sham-operated control group. In contrast, the standard deviation of
      mean arterial pressure, as an index of blood pressure lability, was 3-fold
      greater in SAD rats. To study endothelial function, isometric tension of aortic
      rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent
      vasorelaxation induced by acetylcholine was significantly reduced in the SAD
      group (20% reduction at maximum relaxation). Endothelium-independent
      vasorelaxation induced by sodium nitroprusside was similar in each group.
      Acetylcholine-induced NO release from aortic rings was significantly reduced in
      the SAD group. Next, we examined neointimal formation in carotid arteries in SAD
      and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial
      area ratio in the SAD group was 50% higher than that in the sham-operated group.
      The percentage of proliferating cell nuclear antigen-positive cells in the intima
      was significantly higher in the SAD group. These findings suggest that increased
      blood pressure lability, independently of average blood pressure level, impairs
      endothelial function by inhibiting NO production, enhances neointimal formation
      after balloon injury, and may thereby contribute to atherogenesis.

PMID- 14717343
TI  - Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate
      oxidase in leukocytes of spontaneously hypertensive rats.
AB  - The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the
      pathogenesis of hypertension remains to be elucidated. We analyzed the generation
      of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating
      PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow
      cytometric analysis revealed that ROS generation by PMN from SHR was higher than
      that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset
      of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN
      from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day
      carvedilol, and this treatment did not affect blood pressure. Western blotting
      analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or
      betaII, was activated more strongly in PMN from SHR than in PMN from WKY.
      Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate
      oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from
      WKY. These results suggest that ROS generation by PMN is principally enhanced in
      SHR through activation of PKCalpha and p47phox.

PMID- 14717344
TI  - An assessment of the microbiological risks involved with egg washing under
      commercial conditions.
AB  - The potential benefits of washing eggs is offset by a historical perception in
      the European Union that wetted eggs are prone to spoilage and water loss. This
      study describes the effects of spray jet washing under various processing
      conditions to shell surface counts of Salmonella and the presence of bacteria in
      egg contents. Experiments used eggs that were contaminated with Salmonella
      Enteritidis PT4 or Salmonella Typhimurium DT104 before cuticle hardening. Washing
      of contaminated eggs under optimum conditions resulted in a more than 5-log
      reduction of Salmonella counts from the shell surface. Salmonella was not
      isolated from the yolk or albumen of any egg washed by the optimal protocol,
      suggesting that when properly controlled, egg washing did not cause Salmonella to
      enter the contents. However, contamination did arise if strict control was not
      maintained over the wash and rinse water temperatures. Both Salmonella
      Enteritidis and Salmonella Typhimurium were shown to enter the egg contents when
      water temperatures were lowered, indicating that strict temperature control must
      be maintained in order to prevent the ingress of Salmonella into egg contents.
      Other washing machine parameters that were investigated did not significantly
      affect Salmonella entry into the egg contents but influenced shell surface kill
      levels to varying degrees.

PMID- 14717345
TI  - Independent effects of acetic acid and pH on survival of Escherichia coli in
      simulated acidified pickle products.
AB  - Our objective was to determine the effects of organic acids and pH on the rate at
      which selected strains of Escherichia coli O157:H7 die in acid solutions
      representative of acidified pickle products (pH < 4.6). We used gluconic
      acid/sodium gluconate (pKa = 3.7) as a noninhibitory buffer to maintain pH at
      selected values in the absence of other organic acids. This was possible because
      we found that the inhibitory effects of this acid on E. coli strains at pH 3.1
      were independent of acid concentration over a range of 2 to 200 mM. By this
      method, the lethal effects of acetic acid solutions (100 to 400 mM) at selected
      pH values between 3.1 and 4.1 were compared with the effects of pH alone (as
      determined using gluconate buffer). We found D-values were two- to fourfold lower
      with acetic acid compared with the effect of pH alone for simulated pickle brines
      in this pH range. Glutamic acid, an amino acid that is known to enhance acid
      resistance in E. coli and is a component of pickle brines, protected the E. coli
      strains from the specific effects of acetic acid.

PMID- 14717346
TI  - Impact of cold and cold-acid stress on poststress tolerance and virulence factor
      expression of Escherichia coli O157:H7.
AB  - The effect of extended cold or cold-acid storage of Escherichia coli O157:H7 on
      subsequent acid tolerance, freeze-thaw survival, heat tolerance, and virulence
      factor (Shiga toxin, intimin, and hemolysin) expression was determined. Three E.
      coli O157:H7 strains were stressed at 4 degrees C in TSB or pH 5.5 TSB for 4
      weeks. The acid (TSB [pH 2.0] or simulated gastric fluid [pH 1.5]) tolerance,
      freeze-thaw (-20 degrees C to 21 degrees C) survival, and heat (56 degrees C)
      tolerance of stressed cells were compared with those of control cells. The beta
      galactosidase activities of stressed and control cells containing a lacZ gene
      fusion in the stx2, eaeA, or hlyA gene were determined following stress in TSB or
      pH 5.5 TSB at 37 degrees C and in the exponential and stationary phases. Cold and
      cold-acid stresses decreased acid tolerance (P < 0.05), with a larger decrease in
      acid tolerance being observed after cold stress than after cold-acid stress (P <
      0.05). Cold stress increased freeze-thaw survival for all three strains (P <
      0.05). Prior cold or cold-acid stress had no effect on virulence factor
      production (P > 0.05), although growth in acidic media (pH 5.5) enhanced eaeA and
      hlyA expression (P < 0.05). These results indicate that the prolonged storage of
      E. coli O157:H7 at 4 degrees C has substantial effects on freeze-thaw tolerance
      but does not affect subsequent virulence gene expression.

PMID- 14717347
TI  - Simultaneous detection of Escherichia coli O157:H7, Salmonella, and Shigella in
      apple cider and produce by a multiplex PCR.
AB  - With three pairs of primers, a multiplex PCR assay was established for the
      simultaneous detection of Escherichia coli 0157:H7, Salmonella, and Shigella.
      Under the optimized conditions, the assay yielded a 252-bp product from E. coli
      O157:H7, a 429-bp product from Salmonella Typhimurium, and a 620-bp product from
      Shigella flexneri, respectively. When the DNA extraction of multiple target
      organisms was included in the same reaction, two or three corresponding amplicons
      of different sizes were observed. In the specificity test, 10 E. coli O157:H7
      strains and one E. coli O157:NM strain showed the expected 252-bp amplicon. Seven
      other E. coli strains yielded no signal. Additionally, the 429-bp amplicon was
      produced from 20 Salmonella strains covering 16 serotypes, whereas the 620-bp
      amplicon was generated from 11 Shigella strains covering 4 species. No
      nonspecific amplification was observed with DNA from 48 other bacterial strains.
      Following a 24-h enrichment, the developed assay could concurrently detect the
      three pathogens at initial inoculation levels of approximately 8 x 10(-1) CFU/g
      (or CFU/ml) in apple cider, cantaloupe, lettuce, tomato, and watermelon and 8 x
      10(1) CFU/g in alfalfa sprouts. The whole procedure can be easily completed
      within 30 h. The multiplex PCR assay can potentially be a simple, rapid, and
      efficient tool for presumptive and simultaneous screening of apple cider and
      produce for contamination by E. coli O157:H7, Salmonella, and/or Shigella.

PMID- 14717348
TI  - Intrinsic mechanism decreases susceptibility of Escherichia coli O157:H7 to
      multiple antibiotics.
AB  - Chloramphenicol-resistant mutants of Escherichia coli O157:H7 (n = 52)
      demonstrated multiple resistance to tetracycline, nalidixic acid, and
      ciprofloxacin. Approximately half of the mutants approached the clinical level of
      resistance to the antibiotic tetracycline. Mutants demonstrated a wide range of
      sensitivity to each antibiotic; for tetracycline, some isolates demonstrated a
      twofold increase, whereas others demonstrated a 15-fold increase in resistance.
      Continuous exposure to chloramphenicol did not affect the growth of mutants,
      suggesting that mutation does not have a negative effect on cell survival.
      Complementation experiments with a functional marR restored antibiotic
      susceptibility of selected mutants to levels similar to wild-type strains,
      suggesting that mar mutation was responsible for the decrease in sensitivity. The
      multiple antibiotic resistance (mar) operon is a global regulator controlling
      intrinsic resistance toward structurally and functionally unrelated antibiotics
      and other noxious agents. Antimicrobial use in both human and agricultural
      practice should be administered in a manner to prevent selection of resistant
      mutants.

PMID- 14717349
TI  - Frozen storage of Escherichia coli O157 in buffered peptone water and its
      detection on bovine carcasses.
AB  - The adaptation of a standard Escherichia coli O157 isolation method involving
      immunomagnetic separation and a period of frozen storage was investigated. A
      series of experiments was designed to test the recovery of a bovine strain of E.
      coli O157 from buffered peptone water after a period of frozen storage at -80
      degrees C. The effects of the addition of glycerol at 5 and 10%, freezing time,
      the number of freeze-thaw cycles, the method of freezing and the method of
      thawing, the inclusion of a resuscitation-and-incubation step, and the
      sensitivity of the isolation method were investigated. The most effective method
      of storing frozen samples for 6 months and recovering strains of E. coli O157
      after storage was found to involve 6 h of incubation of sample material in
      buffered peptone water at 37 degrees C before frozen storage at -80 degrees C
      with 10% glycerol, a rapid thaw after frozen storage, and resuscitation at 27
      degrees C for 1 h and incubation at 37 degrees C for 1 h to allow freeze-injured
      and stressed bacteria to recover with a period of growth prior to immunomagnetic
      separation isolation. There was no significant decrease in log counts of a bovine
      strain E. coli O157 over 6 months of frozen storage in buffered peptone water
      with 10% glycerol. With this method, it was possible to isolate E. coli O157 from
      naturally infected bovine carcasses after a period of frozen storage.

PMID- 14717350
TI  - A rapid and automated fiber optic-based biosensor assay for the detection of
      Salmonella in spent irrigation water used in the sprouting of sprout seeds.
AB  - Recent outbreaks of foodborne illness have been linked to the consumption of
      contaminated sprouts. The spent irrigation water used to irrigate sprouts can
      carry many microorganisms, including pathogenic strains of Escherichia coli and
      Salmonella enterica. These pathogens are believed to originate from the seeds.
      The U.S. Food and Drug Administration recommends that sprout producers conduct
      microbiological testing of spent irrigation water from each production lot at
      least 48 h after seeds have germinated. Microbial analysis for the detection of
      Salmonella is labor-intensive and takes days to complete. A rapid and automated
      fiber-optic biosensor assay for the detection of Salmonella in sprout rinse water
      was developed in this study. Alfalfa seeds contaminated with various
      concentrations of Salmonella Typhimurium were sprouted. The spent irrigation
      water was assayed 67 h after alfalfa seed germination with the RAPTOR (Research
      International, Monroe, Wash.), an automated fiber optic-based detector.
      Salmonella Typhimurium could be positively identified in spent irrigation water
      when seeds were contaminated with 50 CFU/g. Viable Salmonella Typhimurium cells
      were also recovered from the waveguides after the assay. This biosensor assay
      system has the potential to be directly connected to water lines within the
      sprout-processing facility and to operate automatically, requiring manual labor
      only for preventative maintenance. Therefore, the presence of Salmonella
      Typhimurium in spent irrigation water could be continuously and rapidly detected
      3 to 5 days before the completion of the sprouting process.

PMID- 14717351
TI  - Modeling the boundaries of growth of Salmonella Typhimurium in broth as a
      function of temperature, water activity, and pH.
AB  - The growth limits of a mixture of five strains of Salmonella Typhimurium in
      tryptic soy broth were examined at different environmental conditions. The
      response of the pathogen was monitored in a total of 350 combination treatments
      of temperature (10 to 35 degrees C), pH (3.76 to 6.44), and water activity (aw,
      0.913 to 0.990) for 62 days. No growth/growth (turbidity) data were modeled by
      logistic polynomial regression. The concordance index of the logistic model was
      99.8%, indicating a good fit to the observed data. The minimum pH and aw values
      that permitted growth were 3.94 and 0.942, respectively, and occurred in the
      temperature range of 25 to 35 degrees C. At temperatures below this range, the
      minimum pH and aw allowing growth increased as the temperature decreased. The
      results showed an abrupt change in the probability of growth close to the
      boundary with minor changes of the environmental factors. The probabilities
      predicted by the model were compared with published data on the actual response
      of Salmonella Typhimurium or other salmonellae serotypes in 50 cases of food
      products, including salad dressing, mayonnaise, meat, cheese, vegetables, and
      fruits. The model predicted successfully the response of the pathogen in 90% of
      the tested cases. The results of the study indicated that the developed model
      predicts satisfactorily the growth/no growth interface of Salmonella Typhimurium
      in foods and can provide useful quantitative data for the development of safer
      food products and processes.

PMID- 14717352
TI  - Thermal inactivation of Enterobacter sakazakii in rehydrated infant formula.
AB  - The presence of low levels of Enterobacter sakazakii in dried infant formula have
      been linked to outbreaks of meningitis, septicemia, and necrotizing enterocolitis
      in neonates, particularly those who are premature or immunocompromised. In the
      current study, the ability of 12 strains of E. sakazakii to survive heating in
      rehydrated infant formula was determined at 58 degrees C with a submerged coil
      apparatus. The observed D58-values ranged from 30.5 to 591.9 s, with the strains
      appearing to fall into two distinct heat resistance phenotypes. The z-value of
      the most heat-resistant strain was 5.6 degrees C. When dried infant formula
      containing this strain was rehydrated with water preequilibrated to various
      temperatures, a more than 4-log reduction in E. sakazakii levels was achieved by
      preparing the formula with water at 70 degrees C or greater.

PMID- 14717353
TI  - Development of predictive models for the survival of Campylobacter jejuni (ATCC
      43051) on cooked chicken breast patties and in broth as a function of
      temperature.
AB  - The objective of this study was to model the kinetics of the survival of
      Campylobacter jejuni on cooked chicken breast patties and in broth as a function
      of temperature. Both patties and broth were inoculated with 10(6) stationary
      phase cells of a single strain of C. jejuni (ATCC 43051) and incubated at
      constant temperatures from 4 to 30 degrees C in 2 degrees C increments under
      aerobic conditions. In most cases, a three-phase linear model fit the primary
      survival curves well (r2 = 0.97 to 0.99) at all incubation temperatures
      regardless of model medium, indicating the presence of a resistant subpopulation
      of C. jejuni that would not be eliminated without thermal processing. Secondary
      models predicting lag time (LT) and specific death rate (SDR) as functions of
      temperature were also developed. The Davey and Boltzmann models were identified
      as appropriate secondary models for LT and SDR, respectively, on the basis of
      goodness of fit (Boltzmann model, r2 = 0.96; Davey model, r2 = 0.93) and
      prediction bias and accuracy factor tests. The results obtained indicate that C.
      jejuni can survive well at both refrigeration and ambient temperatures regardless
      of model medium. Reduced survival of C. jejuni, characterized by shorter lag
      times and faster death rates, was observed both on patties and in broth at
      ambient temperatures. In addition, the average maximum reduction of C. jejuni at
      4 to 30 degrees C was 1.5 log units regardless of storage temperature or model
      medium. These findings suggest that C. jejuni found on contaminated poultry
      products has the potential to survive under conditions that are not permissive
      for growth and thus could cause foodborne illness if the poultry is not
      sufficiently cooked.

PMID- 14717354
TI  - Effect of reheating on viability of a five-strain mixture of Listeria
      monocytogenes in vacuum-sealed packages of frankfurters following refrigerated or
      frozen storage.
AB  - The purpose of this study was to assess consumer preferences for storing and
      reheating frankfurters and to use this information to assess the effect of
      product formulation and storage times and temperatures on the viability of
      Listeria monocytogenes after reheating of frankfurters. Individual links were
      inoculated with about 8.0 log CFU per package of a five-strain mixture of the
      pathogen, vacuum sealed, and stored at 4 degrees C for 3 and 15 days and at -18
      degrees C for 30 days. Frankfurters formulated with and without 2% added
      potassium lactate were heated to a surface temperature of 60, 70, 80, or 90
      degrees C for up to 8 min by submersing the packages in a thermostatically
      controlled circulating water bath. Surviving bacteria were recovered and counted
      by rinsing the contents of each package with sterile peptone water and plating
      this solution directly onto modified Oxford selective agar plates. In general,
      the results revealed that about a 5-log unit reduction was achieved by reheating
      to a surface temperature of 70 degrees C for about 2 min or 80 or 90 degrees C
      for about 0.6 min regardless of storage conditions or formulation. Product
      formulation did not appreciably affect the viability of the pathogen after
      heating; there was no appreciable difference in the number of cells surviving the
      heat treatment in product prepared with or without potassium lactate. These
      findings can be used to establish reheating guidelines for consumers to ensure
      that frankfurters, which may become contaminated with low levels of L.
      monocytogenes prior to packaging and after unpackaging, are adequately reheated
      prior to consumption.

PMID- 14717355
TI  - Reduction and survival of Listeria monocytogenes in ready-to-eat meats after
      irradiation.
AB  - A five-strain Listeria monocytogenes culture was inoculated onto six different
      types of ready-to-eat (RTE) meats (frankfurters, ham, roast beef, bologna, smoked
      turkey with lactate, and smoked turkey without lactate). The meats were vacuum
      packed and stored at 4 degrees C for 24 h prior to irradiation. Populations of L.
      monocytogenes were recovered by surface plating on nonselective and selective
      media. The margins of safety studied include 3-log (3D) and 5-log (5D) reduction
      of pathogenic bacteria to achieve an optimal level of reduction while retaining
      organoleptic qualities of the meats. A 3-log reduction of L. monocytogenes was
      obtained at 1.5 kGy when nonselective plating medium was used. The dosages for 3
      log reduction were 1.5 kGy for bologna, roast beef, and both types of turkey and
      2.0 kGy for frankfurters and ham on the basis of use of selective medium. The D10
      values ranged from 0.42 to 0.44 kGy. A 5-log reduction of L. monocytogenes was
      obtained at 2.5 kGy with nonselective medium. With selective medium, the dosages
      were 2.5 kGy for bologna, roast beef, and both types of turkey and 3.0 kGy for
      frankfurters and ham. Survival of L. monocytogenes in the same RTE meat types
      after irradiation was also studied. Meats were inoculated with 5 log L.
      monocytogenes per g and irradiated at doses of 2.0 and 4.0 kGy. Recovery of the
      surviving organisms was observed during storage at temperatures of 4 and 10
      degrees C for 12 weeks. Preliminary results showed no growth in meats irradiated
      at 4.0 kGy. Survivors were observed for irradiated meats at 2.0 kGy stored at 10
      degrees C after the second week. No growth was observed in samples irradiated at
      2.0 kGy stored at 4 degrees C until the fifth week.

PMID- 14717356
TI  - Growth of heat-treated enterotoxin-positive Clostridium perfringens and the
      implications for safe cooling rates.
AB  - Clostridium perfringens 790-94 and 44071.C05 carrying a chromosomal and a plasmid
      cpe gene, respectively, were used to determine differences in heat resistance and
      growth characteristics between the genotypes. Heat inactivation experiments were
      conducted using an immersed coil apparatus. Spore germination, outgrowth, and lag
      phase, together named GOL time, as well as generation times were determined
      during constant temperatures in fluid thioglycollate (FTG) medium as well as in
      vacuum-packed, heat-treated minced turkey. GOL time and growth were also
      monitored during cooling scenarios from 65 to 10 degrees C for 3, 4, 5, 6, and 7
      h in vacuum-packed, heat-treated minced turkey. Spores of strain 790-94 were
      approximately 10-fold more heat resistant at 85 degrees C than those of strain
      44071.C05, and strain 790-94 also had a higher temperature growth range in FTG.
      The higher growth range for a chromosomal enterotoxin-producing CPE+ strain was
      confirmed using two other strains carrying a chromosomal (NCTC8239) and plasmid
      (945P) cpe gene. Moreover, strain 790-94 had shorter GOL times at 50 degrees C in
      turkey and approximately half the generation time compared with strain 44071.C05
      at temperatures > or = 45 degrees C in both FTG and turkey. Strain 790-94
      increased with 0.3, 1.0, 1.7, and 2.0 logs, respectively, during cooling from 65
      to 10 degrees C in 4, 5, 6, and 7 h, which was significantly higher than for
      strain 44071.C05. A maximum acceptable cooling time of 5 h between 65 and 10
      degrees C is suggested.

PMID- 14717357
TI  - Distribution of aflatoxin-producing Aspergillus flavus and Aspergillus
      parasiticus in sugarcane fields in the southernmost islands of Japan.
AB  - The distribution of Aspergillus flavus and Aspergillus parasiticus in sugarcane
      field soils and on harvested sugarcane stems was studied on seven islands of
      Okinawa and Kagoshima Prefectures, the southernmost prefectures in Japan. With
      the use of a combination of dilution plate and plant debris plate techniques, the
      fungi were detected on all seven islands studied and in 74% of 53 soil samples.
      The fungi were also found on the cut surfaces of sugarcane stems from one of the
      islands. A. parasiticus was the predominant fungus, although many atypical A.
      parasiticus isolates that produced metulated conidial heads were also obtained.
      The proportions of isolates testing positive for aflatoxin production were ca.
      89% (146 of 164) of all isolates and ca. 69% of A. flavus isolates. More than 40%
      of A. flavus isolates also produced G aflatoxins. Scanning electron microscopic
      observation of conidial wall texture was useful in distinguishing A. parasiticus
      from A. flavus. Cyclopiazonic acid, an indole mycotoxin, was never synthesized by
      any of the A. parasiticus or G aflatoxin-producing A. flavus isolates tested.

PMID- 14717358
TI  - Fungi, aflatoxins, and cyclopiazonic acid associated with peanut retailing in
      Botswana.
AB  - Peanuts are important food commodities, but they are susceptible to fungal
      infestation and mycotoxin contamination. Raw peanuts were purchased from retail
      outlets in Botswana and examined for fungi and mycotoxin (aflatoxins and
      cyclopiazonic acid) contamination. Zygomycetes were the most common fungi
      isolated; they accounted for 41% of all the isolates and were found on 98% of the
      peanut samples. Among the Zygomycetes, Absidia corymbifera and Rhizopus
      stolonifer were the most common. Aspergillus spp. accounted for 35% of all the
      isolates, with Aspergillus niger being the most prevalent (20.4%). Aspergillus
      flavus/parasiticus were also present and accounted for 8.5% of all the isolates,
      with A. flavus accounting for the majority of the A. flavus/parasiticus
      identified. Of the 32 isolates of A. flavus screened for mycotoxin production, 11
      did not produce detectable aflatoxins, 8 produced only aflatoxins B1 and B2, and
      13 produced all four aflatoxins (B1, B2, G1, and G2) in varying amounts. Only 6
      of the A. flavus isolates produced cyclopiazonic acid at concentrations ranging
      from 1 to 55 microg/kg. The one A. parasiticus isolate screened also produced all
      the four aflatoxins (1,200 microg/kg) but did not produce cyclopiazonic acid.
      When the raw peanut samples (n = 120) were analyzed for total aflatoxins, 78%
      contained aflatoxins at concentrations ranging from 12 to 329 microg/kg. Many of
      the samples (49%) contained total aflatoxins at concentrations above the 20
      microg/kg limit set by the World Health Organization. Only 21% (n = 83) of the
      samples contained cyclopiazonic acid with concentrations ranging from 1 to 10
      microg/kg. The results show that mycotoxins and toxigenic fungi are common
      contaminants of peanuts sold at retail in Botswana.

PMID- 14717359
TI  - Norovirus cross-contamination during food handling and interruption of virus
      transfer by hand antisepsis: experiments with feline calicivirus as a surrogate.
AB  - While there is good epidemiological evidence for foods as vehicles for norovirus
      transmission, the precise means of spread and its control remain unknown. The
      feline calicivirus was used as a surrogate for noroviruses to study infectious
      virus transfer between hands and selected types of foods and environmental
      surfaces. Assessment of the potential of selected topicals in interrupting such
      virus transfer was also made. Ten microliters of inoculum of feline calicivirus
      deposited onto each fingerpad of adult subjects was allowed to air dry and the
      contaminated area on individual fingerpads was pressed (10 s at a pressure of 0.2
      to 0.4 kg/cm2) onto 1-cm-diameter disks of ham, lettuce, or brushed stainless
      steel. The virus remaining on the donor and that transferred to the recipient
      surfaces was eluted and plaque assayed. Virus transfer to clean hands from
      experimentally contaminated disks of ham, lettuce, and stainless steel was also
      tested. Nearly 46 +/- 20.3, 18 +/- 5.7, and 13 +/- 3.6% of infectious virus was
      transferred from contaminated fingerpads to ham, lettuce, and metal disks,
      respectively. In contrast, approximately 6 +/- 1.8, 14 +/- 3.5, and 7 +/- 1.9%
      virus transfer occurred, respectively, from ham, lettuce, and metal disks to
      hands. One-way analysis of variance test showed that pretreatment (washing) of
      the fingerpads either with water or with both topical agent and water
      significantly (P < 0.05) reduced virus transfer to < or = 0.9%, as compared with
      < or = 2.3 and < or = 3.4% transfer following treatments with either 75%
      (vol/vol) ethanol or a commercial hand gel containing 62% ethanol, respectively.
      Despite wide variations in virus transfer among the targeted items used,
      intervention agents tested reduced virus transfer significantly (P < 0.05) when
      compared with that without such treatments (71 +/- 8.9%). These findings should
      help in a better assessment of the potential for cross-contamination of foods
      during handling and also assist in developing more effective approaches to
      foodborne spread of norovirus infections.

PMID- 14717360
TI  - Comparison of biogenic amine profile in cheeses manufactured from fresh and
      stored (4 degrees C, 48 hours) raw goat's milk.
AB  - In this study, the evolution of microbial counts, biogenic amine contents, and
      related parameters (pH, moisture, and proteolysis) in goat cheese made from fresh
      raw milk or raw milk stored for 48 h at 4 degrees C was examined. In both cases
      the milk was nonpasteurized. This study was designed to evaluate the effect of
      milk quality on the profile of biogenic amines in relation to the evolution of
      the microbial population during cheese making. Cheese made from raw milk stored
      for 48 h at 4 degrees C showed the highest microbial counts and biogenic amine
      levels. The storage of milk under refrigeration caused significant increases in
      the levels of some microbial and biogenic amines during ripening, but not
      initially. Tyramine was the main biogenic amine in the two cheeses tested,
      followed by cadaverine. However, the main differences in amine contents between
      batches were found for putrescine, histamine, and beta-phenylethylamine, whose
      levels were more than twofold higher in samples from raw milk refrigerated for 48
      h than in samples from fresh milk.

PMID- 14717361
TI  - Biogenic amine formation and "zapatera" spoilage of fermented green olives:
      effect of storage temperature and debittering process.
AB  - The effects of temperature and the debittering process on amine formation and
      other chemical changes related to "zapatera" spoilage of fermented green table
      olives during storage, without any chemical correction, were studied. Unwashed
      olive brines were more concentrated in all analyzed compounds, except NaCl. No
      changes in formic, acetic, and succinic acids or in ethanol, hydroxytyrosol, or
      tyrosol were observed in the olive brines during storage. The concentration of
      putrescine in the brine at the beginning of storage and end of fermentation was
      about 38 mg/liter, and it did not change during storage. This amine only seems to
      be produced during the active fermentation phase. The effects of temperature and
      the type of debittering process and time and its interactions (except the time x
      temperature x debittering process on pH) had significant effects on the
      production of cadaverine and tyramine, as well as on changes of pH and lactic and
      propionic acids. Storage at 15 degrees C produced a complete stabilization of the
      fermented olives. However, storage of washed olives at 20 and 28 degrees C
      produced a gradual decrease of lactic acid content, an increase in pH, production
      of propionic acid, and formation of cadaverine and tyramine, the effect becoming
      greater as the temperature rose. It appears that formation of cadaverine and
      tyramine only occurs during storage and might be related to zapatera spoilage.
      Changes were always significantly lower in unwashed olives, which leads to a
      practical stabilization of the product.

PMID- 14717362
TI  - Putrescine, cadaverine, and indole production by bacteria isolated from wild and
      aquacultured penaeid shrimp stored at 0, 12, 24, and 36 degrees C.
AB  - Putrescine, cadaverine, and indole production capabilities of bacteria isolated
      from wild domestic and aquacultured Ni-caraguan penaeid shrimp in progressive
      decomposition states were evaluated. The numbers and types of microorganisms
      responsible for the production of putrescine, cadaverine, and indole in wild and
      aquacultured shrimp increased with increasing decomposition temperature and time.
      Throughout the storage experiments, mean aerobic plate counts (log/g) ranged from
      4.5 to 9.7 and 4.5 to 9.0 for domestic and Nicaraguan shrimp, respectively.
      Vibrio spp. were more prominent in Nicaraguan shrimp (Litopenaeus vannamei) than
      in domestic shrimp (Litopenaeus setiferus and Litopenaeus brasiliensis). The only
      amine-producing (putrescine) microorganism isolated from wild and aquacultured
      shrimp at all temperatures of decomposition (0, 12, 24, and 36 degrees C) was
      Shewanella putrefaciens. On the basis of putrescine production by S. putrefaciens
      at 0 and 12 degrees C and putrescine production by S. putrefaciens, Vibrio spp.,
      and Morganella morganii at 24 and 36 degrees C, putrescine should be considered a
      potential chemical indicator of decomposition in shrimp.

PMID- 14717363
TI  - Effects of on-board and dockside handling on the formation of biogenic amines in
      mahimahi (Coryphaena hippurus), skipjack tuna (Katsuwonus pelamis), and yellowfin
      tuna (Thunnus albacares).
AB  - Consumer illnesses by scombroid poisonings have been a continuing problem for
      many years. The intoxications follow the ingestion of fish such as tuna and
      mahimahi that have undergone bacterial decomposition, leading to the formation of
      biogenic amines. Research studies have concluded that histamine is one of the
      indicators of scombrotoxic fish and that other amines, such as cadaverine, could
      be involved in the illnesses. Guidance for the handling of fish on board fishing
      vessels to prevent the production of scombrotoxic fish has been limited by a lack
      of data addressing changes that occur in fish from the water to delivery at
      dockside. In this study, the changes in selected biogenic amines were determined
      in mahimahi and tuna, which were captured and held in seawater at 25 to 35
      degrees C for incubation times up to 18 h. The fillets from the treated fish were
      sectioned by transverse cuts and analyzed for histamine, cadaverine, and
      putrescine. Results showed that at 26 degrees C, more than 12 h of incubation
      were required before a histamine concentration of 50 ppm was reached in mahimahi.
      At 35 degrees C, 50 ppm histamine formed within 9 h. Similar results were found
      for skipjack and yellowfin tuna. Histamine concentrations exceeded 500 ppm within
      an additional 3 h of incubation in mahimahi. At both temperatures, an increase in
      the concentration of cadaverine preceded an increase in histamine levels. Changes
      in putrescine concentrations in the fish were less pronounced. The study also
      demonstrated that histidine decarboxylase activity was retained in some frozen
      samples of fish and could result in further increases in histamine on thawing.

PMID- 14717364
TI  - Analysis of radiation-induced hydrocarbons and 2-alkylcyclobutanones from dried
      shrimps (Penaeus aztecus).
AB  - We investigated the usefulness of hydrocarbons and 2-alkylcyclobutanones as
      markers for irradiated, dried shrimps. A method was developed to detect the
      irradiation of dried shrimps (Penaeus aztecus) by identifying radiation-induced
      hydrocarbons and 2-alkylcyclobutanones extracted from dried shrimps, which were
      separated by Florisil column chromatography and identified by a method using gas
      chromatography/mass spectrometry. Radiation-induced hydrocarbons and 2
      alkylcyclobutanones are formed from the fatty acids of the irradiated fats. The
      quantity of the hydrocarbons and 2-alkylcyclobutanones formed from some fatty
      acids is related to the composition of fatty acids in a sample. The
      concentrations of hydrocarbons and 2-alkylcyclobutanones increased with radiation
      dose. The major hydrocarbons in the irradiated, dried shrimps were 1-tetradecene
      and pentadecane from palmitic acid; small amounts of heptadecane and 1-hexadecene
      from stearic acid; and 8-heptadecene and 1,7-hexadecadiene from oleic acid. 2-(5'
      Tetradecenyl)cyclobutanone, one of the 2-alkylcyclobutanones, was present at the
      highest concentration. The radiation-induced hydrocarbons and 2
      alkylcyclobutanones were detected at radiation doses of 0.5 kGy and greater.
      These compounds were not detected in nonirradiated, dried shrimps.

PMID- 14717365
TI  - Antimicrobial and antioxidant activities of natural extracts in vitro and in
      ground beef.
AB  - Inhibition of Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria
      monocytogenes by grape seed extract (ActiVin) and pine bark extract (Pycnogenol)
      and the effect of these natural extracts on the oxidative stability of raw ground
      beef were studied. In an agar dilution test, the MICs of ActiVin and Pycnogenol
      were determined to be 4.0 mg/ml for 4.43 log CFU per plate of E. coli O157:H7 and
      4.0 mg/ml for 4.38 log CFU per plate of L. monocytogenes. In an inhibition curve
      test, populations of E. coli O157:H7, Salmonella Typhimurium, and L.
      monocytogenes fell to below the detection limit (10 CFU/ml) after 16 h of
      incubation. The numbers of E. coli O157:H7, L. monocytogenes, and Salmonella
      Typhimurium declined by 1.08, 1.24, and 1.33 log CFU/g, respectively, in raw
      ground beef treated with 1% Pycnogenol after 9 days of refrigerated storage.
      ActiVin (1%) and oleoresin rosemary (1%) resulted in an approximately 1-log CFU/g
      reduction in the populations of all three pathogens after 9 days. The addition of
      1% ActiVin and Pycnogenol contributed to the maintenance of an acidic pH of 5.80
      and 5.58, respectively, in raw ground beef. Compared to the control, all
      treatments increased in L* (lightness), with the exception of ActiVin. ActiVin
      and oleoresin rosemary had the highest a* (redness) and b* (yellowness) values,
      respectively. ActiVin most effectively retarded lipid oxidation, followed by
      Pycnogenol. The results suggest that these natural extracts have potential to be
      used with other preservative methods to reduce pathogenic numbers, lipid
      oxidation, and color degradation in ground beef.

PMID- 14717366
TI  - Antigenotoxic effects of water extract from Korean fermented soybean paste (doen
      jang).
AB  - Aflatoxin B1 is a major metabolite of the toxigenic molds Aspergillus flavus and
      Aspergillus parasiticus. In this study, a bacterial reverse mutation assay with
      Salmonella Typhimurium strains TA1535, TA1537, TA98, TA100, and TA102 and an in
      vitro chromosome aberration test with Chinese hamster lung (CHL) cells were used
      to investigate the genotoxicity of water extract from Korean soybean paste (doen
      jang [dwen-jahng]) and its antigenotoxic activity against aflatoxin B1. The water
      extract itself did not exhibit cytotoxicity or mutagenicity. The extract
      significantly reduced the numbers of revertants when it was added to the assay
      system with Salmonella Typhimurium TA100 (P < 0.05). The extract also exhibited
      significant inhibitory effects on chromosome aberration in CHL cells (P < 0.05).
      Dose-response relationships were observed between the concentration of the water
      extract and both its antimutagenic effect and its suppression of chromosome
      aberration. The results of this work indicate that water extract from Korean
      soybean paste could have potential as an antigenotoxic substance.

PMID- 14717367
TI  - Statistical distributions describing microbial quality of surfaces and foods in
      food service operations.
AB  - Data on the microbial quality of food service kitchen surfaces and ready-to-eat
      foods were collected over a period of 10 years in Rutgers University dining
      halls. Surface bacterial counts, total aerobic plate counts, and total and fecal
      coliform counts were determined using standard methods. Analysis was performed on
      foods tested more than 50 times (primarily lunch meats and deli salads) and on
      surfaces tested more than 500 times (36 different surfaces types, including
      pastry brushes, cutting boards, and countertops). Histograms and statistical
      distributions were determined using Microsoft Excel and Palisades Bestfit,
      respectively. All data could be described by lognormal distributions, once data
      above and below the lower and upper limits of detection were considered
      separately. Histograms for surfaces counts contained one peak near 1 CFU/4 cm2.
      Surfaces with higher levels of contamination tended to be nonmetal, with the
      exception of buffalo chopper bowls, which commonly had high counts. Mean counts
      for foods ranged from 2 to 4 log CFU/g, with shrimp salad, roast beef, and
      bologna having higher means. Coleslaw, macaroni salad, and potato salad (all
      commercially processed products, not prepared in the dining halls) had lowest
      overall means. Coliforms were most commonly found in sealeg salad (present in 61%
      of samples) and least commonly found in coleslaw (present in only 7% of samples).
      Coliform counts (when present) were highest on average in shrimp salad and lowest
      in coleslaw. Average coliform counts for most products were typically between 1
      and 2 log most probable number per gram. Fecal coliforms were not typically found
      in any deli salads or lunch meats.

PMID- 14717368
TI  - Combined effect of electron-beam (beta) irradiation and organic acids on shelf
      life of pork loins during cold storage.
AB  - The combined effects of organic acids and irradiation on shelf life of pork loins
      were examined. Fresh pork loins were sprayed with organic acids (lactic, citric,
      and acetic) at 2%, packaged aerobically, and irradiated with an electron beam at
      1, 2, and 3 kGy. During 14 days of storage, total plate count, coliform number,
      pH, and thiobarbituric acid-reactive substances were measured. Combinations of
      organic acid and irradiation were more effective in reducing and maintaining low
      total plate counts and coliform levels during storage than either treatment
      alone. Higher lipid oxidations were observed in all combination treatments at 1
      day of storage than in the irradiation-only group. However, lower lipid
      oxidations were the result after 14 days of storage when combination treatments
      were used with irradiations of 2 and 3 kGy. Combined treatments involving lower
      irradiation doses than those required for irradiation alone could be used to
      extend the shelf life of pork loins during postirradiation storage without
      increasing lipid oxidation.

PMID- 14717369
TI  - PCR identification of beef, sheep, goat, and pork in raw and heat-treated meat
      mixtures.
AB  - A PCR assay has been developed for the specific and qualitative detection of pork
      (Sus scrofa domesticus), beef (Bos taurus), sheep (Ovis aries), and goat (Capra
      hircus) in raw and heat-treated meat mixtures. A forward common primer was
      designed on a conserved DNA sequence in the mitochondrial 12S ribosomal RNA gene
      (rRNA), and reverse primers were designed to hybridize on species-specific DNA
      sequences of each species considered. The different sizes of the species-specific
      amplicons, separated by agarose gel electrophoresis, allowed clear species
      identification. Analysis of experimental meat mixtures demonstrated that the
      detection limit of the assay was 1% (wt/wt) for each species analyzed. This assay
      can be useful for the accurate identification of these species, avoiding
      mislabeling or fraudulent species substitution in meat mixtures.

PMID- 14717370
TI  - Salmonella in sesame seed products.
AB  - In the context of an international outbreak of multiresistant Salmonella
      Typhimurium DT 104 that was correlated to the consumption of halvah ("helva," an
      Asian candy made from sesame seed), we examined several sesame seed products for
      the occurrence of Salmonella. Of 117 ready-to-eat food items containing sesame,
      we isolated salmonellae from 11 (9.4%) samples. In addition to finding Salmonella
      Typhimurium DT 104 in the halvah involved in the outbreak, we also isolated
      different Salmonella Typhimurium strains out of halvah from other manufacturers
      and countries of origin, as well as Salmonella Offa, Salmonella Tennessee, and
      Salmonella Poona from sesame paste (tahini) and sesame seed, which is sold for
      raw consumption in cereals.

PMID- 14717371
TI  - Evidence of Salmonella internalization into fresh mangos during simulated
      postharvest insect disinfestation procedures.
AB  - A recent U.S. salmonellosis outbreak was epidemiologically associated with
      consumption of imported fresh mangos. Studies were conducted to simulate the
      commercial heat disinfestation method used to eliminate tephritid fly larvae from
      mangos, as well as subsequent product cooling procedures, to assess whether this
      process promotes internalization of Salmonella into mangos. The experimental
      parameters were chosen to mimic the disinfestation method used by the South
      American producer/packer implicated in the recent outbreak. Untreated
      domestically grown immature and ripened Tommy Atkins variety mangos were immersed
      in water at 47 degrees C for 90 min and then immersed in 21 degrees C water
      containing brilliant blue FD&C no. 1 dye for 10 min. After dye internalization
      potential was established (67%), the same experiment was performed using 21
      degrees C water containing 10(7) CFU/ml Salmonella Enteritidis expressing
      constitutive green fluorescent protein. Fruit was then stored at 10, 20, or 30
      degrees C for up to 1 week. Immature and ripened mangos were positive for
      Salmonella internalization at a frequency of 80 and 87%, respectively.
      Internalization frequency into the stem-end segment (83%) was significantly
      higher (P < 0.05) than internalization into the middle-side (19%) or blossom-end
      (9%) segments of the fruit. Salmonella was detected in the mango pulp after 1
      week of incubation. The degree of fruit ripeness, posttreatment holding
      temperature, or duration of storage had no significant effect (P > 0.05) on
      internalization frequency or survival of Salmonella inside mangos. This study
      illustrates the high potential for pathogen internalization if heat-disinfested
      mangos are cooled using contaminated water.

PMID- 14717372
TI  - Bacterial contamination of recirculating brine used in the commercial production
      of moisture-enhanced pork.
AB  - In a commercial process for the production of moisture-enhanced pork, boneless
      pork loins were conveyed through a recirculating injection apparatus, and brine
      (sodium phosphate, sodium chloride, and lemon juice solids) was pumped into the
      meat through banks of needles inserted automatically into the upper surfaces of
      cuts. Brine samples were collected at intervals during the production process and
      analyzed to determine the total plate count and the numbers of lactic acid
      bacteria, pseudomonads, Brochothrix thermosphacta, and Enterobacteriaceae.
      Listeria monocytogenes numbers in the brine were determined using a PCR with
      primers for the hemolysin gene in combination with a most probable numbers
      determination. Maximum numbers of bacteria (log CFU/ml) recovered from the brine
      after 2.5 h of recirculation were as follows: total plate count, 4.50; lactic
      acid bacteria, 2.99; pseudomonads, 3.95; B. thermosphacta, 2.79; and enterics,
      3.01. There was an increase in the number of L. monocytogenes in the
      recirculating brine with time, reaching a maximum of 2.34 log CFU/100 ml after
      2.5 h of moisture-enhanced pork production. Thus, recirculating brines can harbor
      large populations of spoilage bacteria and L. monocytogenes and are an important
      source of contamination for moisture-enhanced pork.

PMID- 14717373
TI  - Enrichment and DNA extraction protocols for the simultaneous detection of
      Salmonella and Listeria monocytogenes in raw sausage meat with multiplex real
      time PCR.
AB  - A novel method of DNA extraction and purification was developed and was used in
      conjunction with a multiplex real-time PCR assay for the simultaneous detection
      of Salmonella and Listeria monocytogenes in a raw meat sample. The PCR used
      primers targeting the invA gene of Salmonella and the hlyA gene of L.
      monocytogenes, and PCR products were detected with a LightCycler on the basis of
      fluorescence from SYBR Green and melting temperature. The assay allowed the
      detection of 3 Listeria cells and 4 Salmonella cells per g of the original
      sausage within 10 h, including an enrichment period of 6 to 8 h.

PMID- 14717374
TI  - Effect of prestorage treatmlents and storage conditions on the survival of
      Salmonella enteritidis PT4 and Listeria monocytogenes on fresh marine and
      freshwater aquaaculture fish.
AB  - The effect of prestorage treatments, such as immersion in a sorbate solution (5%,
      wt/vol), heating (60 degrees C, 1 min), and a combination of the two treatments,
      and the subsequent storage in air or under modified atmosphere packaging (MAP;
      40% CO2, 30% O2, and 30% N2) at chill temperatures (0 +/- 1 degrees C), on
      Listeria monocytogenes and Salmonella Enteritidis PT4 was studied. The prestorage
      treatments affected the pathogenic bacteria, and in all cases, there was a
      decrease in their population, with the sorbate and combination (hot water and
      sorbate) treatment being most effective. The beneficial effect of the prestorage
      treatments, which was more pronounced in storage under MAP conditions, suggests
      an interaction of the treatments with the CO2 of MAP against injured bacterial
      cells.

PMID- 14717375
TI  - Antibacterial efficiency of Finnish spice essential oils against pathogenic and
      spoilage bacteria.
AB  - The antibacterial properties of 13 essential oils, derived from spices grown in
      Finland, were examined with an agar diffusion method against 12 bacterial
      strains. The organisms tested included both spoilage and pathogenic bacteria. The
      gram-positive bacteria appeared to be more sensitive than the gram-negative
      organisms, Clostridium botulinum and Clostridium perfringens being the most
      sensitive. Oregano, savory, and thyme showed the broadest antibacterial activity
      by distinctly inhibiting the growth of all the organisms tested. By gas
      chromatography-mass spectrometry analysis, differences were noted in the
      composition of oregano and thyme oils in comparison to previous reports.

PMID- 14717376
TI  - Comparison of the mouse bioassay and enzyme-linked immunosorbent assay procedures
      for the detection of type A botulinal toxin in food.
AB  - Samples of chili linked to a foodborne illness outbreak of type A botulism were
      examined for preformed type A botulinal toxin using two enzyme-linked
      immunosorbent assay (ELISA) procedures and the mouse bioassay. One of the samples
      was positive for type A botulinal toxin and three of the samples were negative
      for type A, B, E, and F botulinal toxins using the three methods. The mouse
      bioassay indicated that type A toxin was present at the 10,000 minimal lethal
      dose per gram (MLD per g) of product. The ELISA tests indicated a toxicity of
      7,650 MLD per g with one method and 8,350 MLD per g with the other method. The
      sample toxicity determined by the ELISA was estimated by comparing samples to a
      standard curve generated with standard type A neurotoxin in casein buffer. The
      ELISA methods are more rapid than the mouse bioassay, since the toxin type can be
      determined in 1 day. The mouse bioassay is more sensitive than the ELISA but
      usually requires multiple assays to obtain the toxin type and toxicity. Type A
      culture isolates from the sample were also verified using one ELISA method.

PMID- 14717377
TI  - Selective efficacy of culture media recommended for isolation and enumeration of
      Fusarium spp.
AB  - Selective culture media, such as Nash and Snyder medium (NS), dichloran
      chloramphenicol peptone agar (DCPA), modified Czapek-Dox agar (MCz), Czapek Dox
      iprodione dichloran agar (CZID), potato dextrose iprodione dichloran agar (PDID),
      or malachite green agar (MGA 2.5), have been developed for isolating and
      enumerating Fusarium spp. from natural samples. However, some of these culture
      media are not very selective because they allow the growth of many other fungal
      species. In this study, a comparison of the selective efficacy of these culture
      media, using different strains of Fusarium spp. (F. anthophilum, F. culmorum, F.
      dlamini, F. graminearum, F. napiforme, F. nygamai, F. oxysporum, F. proliferatum,
      F. semitectum, F. solani, F. subglutinans, and F. verticillioides) and natural
      samples has been carried out. Among the six recommended selective culture media
      assayed, no statistical differences were detected in colony counts of the
      Fusarium spp. strains tested, although the colony diameters in MGA 2.5 were
      significantly lower than in NS, MCz, DCPA, CZID, and PDID media. With natural
      samples, MGA 2.5 performs as a potent selective medium for Fusarium spp., whereas
      the other recommended selective media allow the growth of many other different
      fungal species including Zygomycetes and yeasts.

PMID- 14717378
TI  - Simplified qualitative method for canavanine in seeds and sprouts.
AB  - The major stored nitrogen compound in alfalfa seeds is canavanine. To identify
      this nonprotein amino acid from seed extract and sprout water, a qualitative
      micro-thin-layer chromatography method was developed. Successful separation and
      identification was achieved using microsilica plates, a 70:30 ethyl alcohol-water
      solvent system, and 1% ammonium disodium pentacyanoammineferrate II for color
      development. This quick method was used to identify canavanine (sensitivity 50
      microg) from irradiated and nonirradiated alfalfa and clover seed extracts and
      alfalfa sprout water. Broccoli and radish seed extracts were negative for
      canavanine. This simple method is useful to track the release and decrease of
      canavanine in the sprout water.

PMID- 14717379
TI  - On patient satisfaction surveys.

PMID- 14717380
TI  - Commentary: a patient-centered theory of satisfaction.
AB  - The Primary Provider Theory holds that patient satisfaction occurs at the nexus
      of provider power and patient expectations. More specifically, patient
      satisfaction is principally the function of an underlying network of interrelated
      satisfaction constructs--satisfaction with the primary provider, waiting for the
      provider, and satisfaction with the provider's assistant(s). Hierarchically
      linked to patient-centered expectations of provider value, the Theory specifies
      that primary providers offer the greatest clinical utility to patients. The
      Theory is operationalized by patient-centered measures exclusively, where only
      patients judge the quality of service and all other judgments are immaterial.
      Bearing in mind the Institute of Medicine's recent recommendations to clinicians
      regarding the implementation of a new level of patient-centered care, the Primary
      Provider Theory offers an alternative paradigm for the measurement and
      realization of patient satisfaction. It can inform patient-centered physician
      practice, medical education, quality improvement, outcome measurement, and
      satisfaction survey construction.

PMID- 14717381
TI  - A patient satisfaction theory and its robustness across gender in emergency
      departments: a multigroup structural equation modeling investigation.
AB  - This investigation tested the patient-centered Primary Provider Theory of Patient
      Satisfaction across gender in national random samples of emergency patients.
      Using multigroup structural equation modeling, the results supported the model's
      robustness. Physician service, waiting time, and nursing satisfaction explained
      48%, 41%, and 11% of overall satisfaction plus 92% and 93% of female and male
      satisfaction, respectively. Unit increases in physician service satisfaction
      increased waiting time, nursing, and overall satisfaction by 0.991, 0.844, and
      1.031 units, respectively. Unit increases in waiting time satisfaction increased
      nursing and overall satisfaction by 0.417 and 0.685 units, respectively. A unit
      increase in nursing satisfaction increased overall service satisfaction by 0.221
      units. The investigation offers an alternative paradigm for measuring and
      achieving emergency department satisfaction, hierarchically related to patient
      expectations, where the primary provider has the greatest clinical utility to
      patients, followed by waiting for the primary provider, and then by nursing
      service.

PMID- 14717382
TI  - Perceptions of care of patients undergoing coronary artery bypass surgery in
      Veterans Health Administration and private sector hospitals.
AB  - Few studies have examined differences in patient perceptions of care between
      health care systems. This study compared the perceptions of male patients
      undergoing coronary artery bypass graft surgery in 43 Veterans Health
      Administration (VA) hospitals (N = 808) and 102 US private sector hospitals (N =
      2271) from 1995 to 1998. Patient perceptions were measured by a validated survey
      that was mailed to patients after discharge. For 8 of the 9 dimensions assessed
      by the survey, VA patients were more likely (P < .001) than private sector
      patients to note a problem with care (eg, Coordination, 48% versus 40%; Patient
      Education and Communication, 50% versus 40%; Respect for Patient Preferences, 49%
      versus 41%). In comparisons limited to major teaching hospitals, VA patients were
      more likely to note a problem for 5 dimensions. The findings indicate that
      patient perceptions of care may be lower in VA than in private sector hospitals.
      Future studies should examine whether the VA's recent focus on improving patient
      satisfaction has narrowed these differences.

PMID- 14717383
TI  - Primary care clinic size and patient satisfaction in a military setting.
AB  - Patient satisfaction is a fundamental parameter of quality in health care.
      Identification of aspects of care that influence patient satisfaction may be used
      to design changes in health delivery systems, thus improving quality of care. The
      objective of this study was to examine the relationship between the patient's
      assessment of quality of health care and the size of primary care clinics (PCCs)
      (measured as number of monthly patient visits) as well as the physician workload
      (measured as number of visits per physician per month). This study was a cross
      sectional study using PCCs' characteristics and patient satisfaction surveys. One
      hundred one PCCs were evaluated. There was a negative correlation between all
      satisfaction indices and the number of primary care physicians in the clinic and
      the number of monthly visits to the clinic. In contrast, there was no significant
      correlation between the actual workload per physician. In general linear models,
      clinic size correlated significantly and negatively with patient satisfaction
      even after correction for other factors. The study concluded that patient
      satisfaction in the medical settings of the Israel Defense Forces is adversely
      affected by large clinic size but is not affected by physician workload.

PMID- 14717384
TI  - Patient satisfaction instruments used at academic medical centers: results of a
      survey.
AB  - As physicians and health administrators increasingly incorporate patients'
      perspectives into health care, patient satisfaction has become a significant
      health care outcome. However, there is limited knowledge regarding the patient
      satisfaction instruments being used by leading academic medical centers. The
      objective of this study was to determine the types of patient satisfaction
      instruments used by leading academic medical centers. We conducted a telephone
      survey of 16 leading academic medical centers across the United States to
      determine the types of patient satisfaction instruments used at each institution
      for outpatient and inpatient care. Among the institutions surveyed, a
      significantly higher proportion used internally developed surveys for
      satisfaction measurement among outpatients than for satisfaction measurement
      among inpatients. Although much attention has been focused on patient
      satisfaction in recent years, there is little standardization of the patient
      satisfaction instruments currently being used at the academic medical centers
      surveyed, particularly for outpatient care. This lack of standardization limits
      opportunities for benchmarking of patient satisfaction data among peer
      institutions and may limit efforts to improve care.

PMID- 14717385
TI  - Ventricular remodeling.
AB  - Ventricular remodeling is an extremely complicated process that is not well
      understood. There seem to be multiple feedback loops that respond to mechanical
      events as well as to neurohormonal stimulation, cytokine release, and other, yet
      unidentified, agents. The progression of ventricular remodeling after the index
      event includes: Myocyte slippage and thinning of infarct area, chamber
      dilatation. Fibrosis and scar formation. Collagen strut dissolution and excessive
      accumulation of interstitial matrix. Increased wall stress. Myocyte hypertrophy.
      Neurohormonal activation. Cytokine release. Ongoing myocyte hypertrophy. Cell
      apoptosis and necrosis. Continued deterioration of cardiac function. It is
      impossible to place the sequence of events in order, because the multiple
      feedback systems create a complex interactive process. A basic awareness of the
      pathophysiology of ventricular remodeling can aid in understanding current and
      future treatments for heart failure. It is clear that therapeutic interventions
      solely aimed at improving cardiac pump function do not slow the progression of
      heart failure or reduce mortality. Drugs that block the neuroendocrine
      contribution to the remodeling process have been shown to have a greater impact.
      Current therapies with angiotensin-converting enzyme inhibition, beta blockade,
      and aldosterone antagonism are associated with significant reductions in
      morbidity and mortality in heart failure. Other therapeutic strategies suggested
      by knowledge of remodeling mechanisms, such as drugs to block cytokines,
      endothelins, and MMPs, may offer further benefit to patients with heart failure
      in the future.

PMID- 14717386
TI  - Neurohormone activation.
AB  - Neurohormonal activation plays a significant role in left ventricular remodeling
      and progression of heart failure. Treatment strategies that antagonize the RAS
      and sympathetic nervous system can attenuate the left ventricular remodeling
      process. Natriuretic peptides, specifically BNP, are a marker of left ventricular
      dysfunction. With the progressive increase in the incidence and prevalence of
      heart failure, treatment approaches must focus on the underlying cause as well as
      on blocking the neurohormonal activation that leads to the remodeling process.

PMID- 14717387
TI  - Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers:
      what we know and current controversies.
AB  - A little more than a decade ago, management of heart failure was changed forever
      when a number of randomized clinical trials confirmed that a class of drugs,
      angiotensin-converting enzyme (ACE) inhibitors, could improve survival in
      patients with heart failure. The recognition that blockade of one of the
      neurohumoral systems activated in heart failure could improve outcomes prompted
      widespread testing of other neurohumoral blockers, such as beta-adrenergic
      blocking agents, aldosterone antagonists, and most recently, angiotensin II type
      1 receptor blockers (ARBs) for the treatment of heart failure. This article
      describes what is known about the use of ACE inhibitors and ARBs in the
      management of heart failure and presents the current controversies surrounding
      the use of these agents.

PMID- 14717388
TI  - The use of beta-blockers in the treatment of chronic heart failure.
AB  - The use of beta-blockers in addition to digoxin, diuretics, and ACE inhibitors
      was shown to be beneficial for patients with chronic heart failure. Benefits
      include decreased hospitalizations, decreased need for heart transplant, and
      decreased mortality. The fact that beta-blockers may improve a sense of well
      being, as well as quality of life, for patients with chronic heart failure, is
      perhaps the greatest advantage to including these drugs in HF therapy.

PMID- 14717389
TI  - Digoxin in heart failure.
AB  - Digoxin is an agent with a long history of use in the management of heart
      failure; its benefits have just been quantified in recent years. It has long been
      known that digoxin provides a small amount of inotropic augmentation; however, it
      is now realized that digoxin also modulates the neurohormonal activation that
      occurs in heart failure. Although long-term therapy with digoxin does not
      decrease mortality, it does provide clinical benefit in terms of improved
      exercise tolerance and decreased hospitalizations across all severities of heart
      failure. Serum concentrations of digoxin associated with clinical benefits are
      lower than previously recognized (0.8-1.0 ng/mL). Digoxin toxicity can be easily
      avoided by maintaining these relatively low serum concentrations, avoiding and
      aggressively treating hypokalemia, and being mindful of poor renal function and
      drug interactions that may result in digoxin accumulation.

PMID- 14717390
TI  - Rational diuretic management in congestive heart failure: a case-based review.
AB  - The pharmacology and pharmacokinetics of diuretics are unique among therapeutic
      drugs. Knowledge of these principles can be used to great advantage in the
      management of heart failure, whereas ignoring them can lead to either minor or
      life-threatening adverse consequences. Two major categories of potential
      therapeutic problems are diuretic resistance and the development of disturbances
      in serum potassium and other electrolytes. Inhibition of sodium reabsorption in
      the loop of Henle or distal convoluted tubule leads to renal potassium wasting,
      whereas inhibition of sodium reabsorption in the collecting duct (either
      directly, as with triamterene or amiloride, or through aldosterone antagonism)
      causes potassium retention. Combining diuretics of different classes, a rational
      and frequently used strategy to counter diuretic resistance, can be anticipated
      to balance or magnify these effects, depending on the site of action of the
      individual drugs.

PMID- 14717391
TI  - The role of B-type natriuretic peptide in heart failure.
AB  - The use of BNP as a diagnostic and therapeutic tool in the management of heart
      failure is promising. Additional studies need to be done regarding the use of BNP
      as a diagnostic tool to clarify its intrapatient and interpatient variability,
      especially over time. Nesiritide is the first new intravenous agent for the
      treatment of acute decompensated heart failure since the introduction of
      milrinone. It is an effective vasodilator and enhances the effect of concomitant
      diuretic therapy. Nesiritide may have some benefit on long-term outcomes by
      prolonging survival, decreasing hospitalizations, or enhancing quality of life.
      Whether it can or should be used as chronic therapy in end-stage patients remains
      to be determined.

PMID- 14717392
TI  - Resynchronization therapy for the management of heart failure.
AB  - Biventricular pacing offers real benefit to some patients with HF, but several
      questions remain unanswered. One is which patients will benefit the most from
      this technology. Although there are some indications, the ideal patient group has
      yet to be identified. The best electrical configuration for pacing and the best
      pacing site have not been identified for all patients. Another question is
      whether resynchronization will improve mortality rates. A final question is the
      cost-effectiveness of this therapy. Studies in progress may answer some of these
      questions. Meanwhile, this intervention offers hope for improved quality of life
      and perhaps survival in this high-risk patient population.

PMID- 14717393
TI  - Surgical management of heart failure.
AB  - This article introduces the mechanisms and theories behind the surgical
      treatments for heart failure; however, heart failure is a complex problem and
      requires multiple solutions. Surgery offers treatment strategies that target
      underlying physiologic changes and may provide both quality of life and survival
      benefit to patients who have specific clinical characteristics consistent with
      the aims of the procedure. Nurses must include surgical treatment early in their
      hierarchy of treatment plans, especially when coronary artery occlusion,
      hibernating myocardium, or mitral valve regurgitation is the cause of heart
      failure. In addition, newer investigational surgical therapies must also be
      considered for patients with advanced heart failure who have already been
      optimized on medical and cardiac resynchronization therapies and who require a
      novel approach to potentially improve individual outcomes.

PMID- 14717394
TI  - Heart transplantation an answer for end-stage heart failure.
AB  - Heart transplantation remains the best treatment option for end-stage heart
      failure. For patients who are not candidates for transplantation, better medical
      management and surgical options in heart failure can improve both the length and
      quality of a patient's life. Continuing research on xenotransplantation and the
      total artificial heart may decrease the need for human transplantation in years
      to come and may allow others with severe heart failure to have a chance at living
      longer.

PMID- 14717395
TI  - Diastolic dysfunction.
AB  - Although the annual mortality rate for diastolic heart failure is better than
      that for systolic heart failure, it is still greater than that for age-matched
      controls. Five-year mortality rates are about 50% for patients with systolic
      heart failure and are about 25% for patients with diastolic heart failure. In
      elderly patients (over 65 years of age), the outcome with systolic and diastolic
      dysfunction may be more comparable. In contrast to systolic heart failure, the
      effect of therapy in patients with diastolic heart failure has not been evaluated
      in large clinical controlled trials. Guidelines for managing heart failure with
      preserved systolic function broadly suggest the direction for management, but
      specific treatments are currently based on expert consensus, clinical experience,
      and scientific elucidation of diastolic mechanics. Although evidence-based
      guidelines are not available for all aspects of management of diastolic heart
      failure, future research will increase the knowledge of this disorder and improve
      treatment strategies.

PMID- 14717396
TI  - Outpatient management of chronic heart failure.
AB  - Critical to the success of managing heart failure is appropriate outpatient
      follow up. Various models of care integrate medical care, pharmacologic
      intervention, and patient education and support. Key factors in any program are
      frequent patient assessment with rapid response to even subtle changes in the
      patient's condition. As the disease progresses, alternative care options such as
      palliative care and hospice should be integrated into the patient's care regimen.

PMID- 14717397
TI  - Quality of life when living with heart failure.
AB  - Heart failure is a chronic condition and consumes a huge portion of health care
      expenditures. Increased life expectancy combined with increasingly effective
      treatments for coronary artery disease and hypertension will increase the number
      of patients with heart failure. Efforts are aimed at helping patients better care
      for themselves. Nurses can design interventions that focus on education and self
      management of complex treatments, spiritual support, and clinical relationships
      based on trust. It is essential that health care providers direct and evaluate
      interventions that promote improved QOL for patients and families. Nurses also
      need to continue to study the effects of education and self-care interventions so
      that care for heart failure patients is evidence based.

PMID- 14717398
TI  - Case studies in heart failure.
AB  - This article presents four case studies of patients with heart failure and the
      rationale for optimal treatment in each case.

PMID- 14717399
TI  - Future therapies for heart failure.
AB  - The treatment of heart failure has changed as the understanding of the disease
      evolves. Heart failure remains the only cardiovascular disease that continues to
      rise in both incidence and prevalence, despite recent advances in treating
      symptoms and thwarting disease progression. Many opportunities exist for
      improving patient outcomes with pharmaceutical agents and technologies available
      now or in the near future. This article discusses recently approved drugs and
      devices and clinical trials that may affect the management of this challenging
      disease.

PMID- 14717400
TI  - Structure and function of ethnic skin and hair.
AB  - Differences have been found among blacks, whites, Asians, and Hispanics in
      various areas of skin structure and function. Among them is the stratum corneum
      lipid (ceramide) content, which is highest in Asians, then Hispanics, then
      whites, and lowest in blacks. Melanosomal packaging and percutaneous absorption
      rates for specific compounds also vary among the different races. Reports
      supporting the occurrence of difference in TEWL, tyrosinase levels, skin
      elasticity, and water absorption rates between blacks and whites, and reaction to
      skin irritation have been conflicting. No significant differences in corneocyte
      size, skin thickness, and skin biomechanics have been reported.

PMID- 14717401
TI  - Epidemiology of skin diseases in ethnic populations.
AB  - The spectrum of cutaneous disease occurring in ethnic populations is as broad and
      diverse as the ethnic populations themselves. Many skin diseases are seemingly
      common to most of the ethnic populations, however, including blacks, Hispanics,
      Asians, and Native Americans. These diseases include acne vulgaris; pigmentary
      disorders; eczematous dermatitis; and infection caused by bacteria, fungi, and
      viruses. Diseases of a more cosmetic nature have emerged over recent years and
      include the pigmentary disorders melasma and postinflammatory pigmentation, acne
      keloidalis nuchae, scalp and facial folliculitis, keloidal scarring, alopecia,
      and photoaging. The identification of cutaneous diseases affecting the rapidly
      increasing ethnic populations serves to focus resources both research and
      clinical in these areas.

PMID- 14717402
TI  - Acne in ethnic skin.
AB  - Acne is the most common disorder observed in ethnic skin. Clinical presentation
      is different than in white skin. Postinflammatory hyperpigmentation is a common
      sequelae of acne in darker skin. The management of acne in ethnic skin is based
      largely on the prevention and treatment of hyperpigmentation.

PMID- 14717403
TI  - Pigmentary disorders in ethnic skin.
AB  - Pigmentary disorders are commonly seen in ethnic skin. They are psychologically
      problematic in darker skin. Treatment of many of these disorders remains
      difficult.

PMID- 14717404
TI  - Hair and scalp disorders in ethnic populations.
AB  - Treating scalp and hair disorders is challenging because of the emotional nature
      of hair loss and because of unknown pathogenesis. Treating African American
      patients can add an extra layer of complexity to this treatment if the
      dermatologist is not familiar with hair care practices. Only the dermatologist
      who strives to understand hair care practices, the common disease entities of the
      hair and scalp in African Americans, and the disturbance in quality of life from
      alopecia will effectively approach treatment in these patients.

PMID- 14717405
TI  - Pseudofolliculitis barbae and acne keloidalis nuchae.
AB  - There is therapeutic and help and hope for AKN patients using the excision and
      second-intention healing technique, plus some of the recently reported laser
      techniques.

PMID- 14717406
TI  - New and re-emerging cutaneous infectious diseases in Latin America and other
      geographic areas.
AB  - Due to environmental factors and inadequate public health measures in many
      developing countries, new tropical infections, as well as infections that were
      previously isolated to remote locales, are becoming more prevalent in several
      areas of Latin America. This article discusses some tropical infections and
      infestations with predominantly cutaneous manifestations. Previously uncommon
      diseases such as gnathostomiasis, mycobacteria ulcerans infection, paederus
      dermatitis, Balamuthia mandrillaris infection, and human T-lymphotrophic virus 1
      dermatitis are increasingly being reported. Well-known tropical infections such
      as bartonellosis, leishmaniasis, chromomycosis, larva migrans, and larva currens
      are also becoming more prevalent. On the other hand, the incidence of Hansen's
      disease, the quintessential tropical infection, is dwindling all over the globe
      thanks to a highly effective eradication campaign launched by the World Health
      Organization. Because of increased immigration and tourist travel, the number of
      cases of these diseases in the United States may escalate.

PMID- 14717407
TI  - Cutaneous diseases in Asians.
AB  - Atopic dermatitis, nummular dermatitis, dyshidrosis, and melasma seem to be more
      common in Asians, whereas psoriasis and skin cancer are less common. In addition,
      there are less common skin conditions that are usually seen in Asians, including
      Mongolian spot, nevus of Ota, nevus of Ito, Kawasaki disease, primary cutaneous
      amyloidosis, Kikuchi-Fujimoto disease, and LCAI. Awareness of these less common
      cutaneous disorders can be helpful, especially for clinicians who work in areas
      with a large Asian population.

PMID- 14717408
TI  - Cutaneous diseases in the black races.
AB  - Laser therapy is routinely used today to treat a myriad of general and cosmetic
      dermatologic conditions. Most laser procedures are performed on lighter skin
      types with an abundance of published literature. There is a dearth of information
      about lasers on darker ethnic skin types. The demand for laser procedures on
      ethnic skin is growing dramatically. The dermatologic surgeon needs a
      conservative approach combined with ingenuity, sound judgment, and a clear
      understanding of laser optics in treating ethnic skin.

PMID- 14717409
TI  - Cutaneous diseases in Latinos.
AB  - The knowledge of many specific skin diseases that predominantly affect Latinos
      has been increasing; however, the understanding of common skin disease in Latinos
      is superficial. There are few prospective studies done in the Latino population
      and none that differentiate between diverse Latino backgrounds. In view of the
      expanding Latino population in this country, such research is timely.

PMID- 14717410
TI  - Cutaneous diseases in Native Americans.
AB  - Native Americans have a rich and complex heritage and culture. Although the
      genetic pool has changed with increasing integration with other Americans with
      different ancestry, there are important conditions that are unique to Native
      Americans, the most prominent example being actinic prurigo. The scientific
      literature dealing with Native American skin conditions is sparse and more
      studies are needed to understand more fully cutaneous disease in Native
      Americans.

PMID- 14717411
TI  - Cosmetic considerations and nonlaser cosmetic procedures in ethnic skin.
AB  - The face of the aesthetic patient is changing to be more representative of the
      ethnic diversity of the United States population. It is imperative that the
      cosmetic dermatologic surgeon not only understand the concerns of the ethnic
      aesthetic patient but have an awareness of the unique needs of those with darker
      skin.

PMID- 14717412
TI  - Laser therapy on darker ethnic skin.
AB  - Like all medical procedures laser therapy comes with inherent risks and
      complications. Because of the increased risk in epidermal side effects when
      performing laser therapy on patients with darker skin, a higher level of laser
      expertise and clinical experience in treating darker ethnic skin is recommended
      to ensure that patients are treated safely. Test spots should always be done as
      an aid to selecting safe and efficacious treatment parameters. Because of the
      limited experience in treating patients with darker skin a conservative approach
      should always be used. Unfortunately, there are no national policies establishing
      credentialing requirements for those planning to practice laser surgery. The US
      Food and Drug Administration are responsible for granting individual laser
      manufacturers' permission to market their lasers for specific indications. The
      Food and Drug Administration also recommends operator training to use these
      lasers, but credentialing is a state function and consequently standards for
      laser therapy vary greatly from state to state. Until the bar is raised and
      national credentialing polices on laser therapy are established clinicians must
      police themselves and fully be aware of their capabilities and limitations to
      ensure that all patients regardless of skin color or ethnicity receive safe and
      effective treatments.

PMID- 14717413
TI  - Skin cancer and photoaging in ethnic skin.
AB  - Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma,
      hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most
      serious types of skin cancer noted in the darker-skinned population. Photoaging
      occurs less frequently and is less severe in ethnic skin.

PMID- 14717414
TI  - Cultural aspects in the treatment of patients with skin disease.
AB  - As the cultural distance between patient and physician widens, so does
      miscommunication. Negotiation between the belief systems of the physician and the
      patient may create a therapeutic environment of mutual trust and respect that
      increases the possibility of successful clinical outcomes.

PMID- 14717415
TI  - Ethnic cosmetic products.
AB  - Based both on actual differences in the hair and skin and on cultural desire,
      people of color do have special considerations for cosmetic products. As the
      experts in hair and skin, it is incumbent on dermatologists to understand the
      needs of a diverse patient base, to be knowledgeable about the products that
      patients need and desire, and to be aware of possible adverse effects related to
      product use or misuse. Further research is needed both to continue to understand
      the needs of the hair and skin of people of color and to understand the effects
      of products on ethnic hair and skin.

PMID- 14717416
TI  - Impact of collagen-coated and gelatine-impregnated woven Dacron branched grafts
      on the early postoperative period.
AB  - To investigate the impact of two different sealed Dacron vascular branched
      prostheses on the early postoperative period, 30 patients whose aortic arch was
      replaced by either a collagen-coated (n=18) or a gelatine-impregnated (n=12)
      branched prosthesis were retrospectively studied. The patients who received a
      collagen-coated branched prosthesis required longer chest drainage (11.9+/-5.2
      vs. 7.9+/-4.6 days, p<0.05). On the other hand, higher white cell count on 7th
      postoperative day (9,406+/-3,485 vs. 11,810+/-4,378/microL, p<0.05) was observed
      in the patients with a gelatine-impregnated branched prosthesis. Biocompatibility
      of the prostheses could affect the early postoperative course, therefore these
      specific impacts should be considered to manage the patients with these
      prostheses.

PMID- 14717418
TI  - Less invasive surgical closure of patent ductus arteriosus in extremely low birth
      weight infants.
AB  - Minimally invasive surgery is widely used in pediatric surgery. Extremely low
      birth weight infants (ELBWI) are literally so fragile to surgical stress that the
      minimum invasive procedures should be required. We report 15 ELBWI cases with
      patent ductus arteriosus (PDA), who underwent surgical closure. All of them had
      failed treatment with indomethacin to close PDA or had contraindicated to its
      use. The mean gestational age at birth was 26.0+/-2.7 weeks (24-34 weeks) and
      birth weight 702+/-140 g (479-966 g). The mean age at operation was 23+/-11 days
      (2-48 days) and body weight at operation 679+/-151 g (428-969 g). The surgery
      related mortality was none. No complications were also encountered. Our surgical
      procedures consist of 2 modalities, one is clipping PDA, not ligation. Clipping
      technique attributes to minimize the dissection of surrounding tissue of PDA. The
      other is posterolateral muscle sparing thoracotomy, which would reduce long-term
      physical impairment and deformity. We believe our surgical technique can be
      accomplished safely and would be an alternative approach for ELBWI with a lower
      probability of PDA closure with indomethacin or an increased risk of
      complications for medical treatment.

PMID- 14717417
TI  - Video-assisted thoracic surgery for lung cancer: is it a feasible operation for
      stage I lung cancer?
AB  - OBJECTIVE: The objective of this study was to confirm the safety and feasibility
      of video-assisted thoracic surgery (VATS) for primary lung cancer and to compare
      prognoses with that of conventional procedures, and then to examine whether VATS
      would supplant a conventional thoracotomy for stage I lung cancer. METHODS: From
      September 1995 through March 2002, 144 patients with primary lung cancer,
      included 118 patients with postoperative stage I, underwent VATS lobectomy. We
      reviewed the previous cases whether they could be candidates for VATS lobectomy
      according to present indications. 166 cases were supposed to be candidates for
      VATS, and 121 cases of postoperative stage I disease were recruited into the
      "conventional thoracotomy" group. RESULTS: There was no mortality or major
      complication except one case, and mean follow-up was 31.8 months in VATS. The
      number of removed lymph nodes was not significantly less than the number by
      conventional thoracotomy (p=0.061). Five-year survival for patients with
      pathological stage IA adenocarcinoma was 92.4% (n=66) in VATS and 86.9% (n=50) in
      conventional thoracotomy, and a statistical significance could not be recognized
      (p=0.980). The length of hospital stay was significantly short in VATS lobectomy
      (p<0.0001). CONCLUSIONS: VATS lobectomy for stage I lung cancer can be performed
      safely with minimal morbidity, satisfying survival comparable with that of
      lobectomy through conventional thoracotomy. VATS approach is a feasible surgical
      technique for patients with stage I lung cancer.

PMID- 14717419
TI  - Diagnosis and surgical treatment of ectopic adrenocorticotropic hormone-producing
      pulmonary tumors accompanied by Cushing syndrome.
AB  - Malignant pulmonary tumors are rarely accompanied by Cushing syndrome. We
      encountered 4 patients with adrenocorticotropic hormone (ACTH)-producing
      pulmonary tumors (3 with carcinoid and 1 with small cell carcinoma). All patients
      were females aged 33-76 years. In the 4 patients, diagnostic methods, surgical
      procedures, stage, outcome, and immunohistological findings were evaluated.
      Subtotal resection of the anterior lobe of the pituitary gland had been performed
      in 3 patients. However, ACTH did not decrease, and further examination revealed
      pulmonary tumors. Preoperative blood sampling by catheter examination was
      performed in 2 patients, of whom 1 showed increased ACTH. Intraoperative blood
      sampling showed increased ACTH in 1 patient. Lobectomy combined with mediastinal
      lymph node dissection was performed in 3 patients and lobectomy alone (video
      assisted thoracoscopic surgery) in 1. All patients showed a decrease in ACTH
      after operation without tumor recurrence. Diagnosis is possible by measuring ACTH
      in pulmonary arterial wedge blood obtained by catherization or in pulmonary
      venous blood obtained during operation. Surgical resection is effective for
      ectopic ACTH-producing pulmonary tumors.

PMID- 14717420
TI  - Spontaneous regression in small cell esophageal carcinoma.
AB  - Spontaneous regression or remission of cancers has been defined as the
      disappearance of the malignancies without any treatment or with obviously
      inadequate treatment. Spontaneous regression is rare, while any case with a small
      cell carcinoma in the esophagus was not found in the literature. We experienced a
      73-year-old man with small-cell carcinoma in the thoracic esophagus whom
      underwent esophagectomy with lymphadenectomy. A pathological examination of the
      resected specimens found metastasis from the small cell carcinoma in the
      mediastinal lymph nodes, but no malignant cells in the esophageal lesion--an
      ulcer scar from which the biopsy specimen was taken to be a small-cell carcinoma.
      This may be the first case report that spontaneous regression in a small-cell
      carcinoma in the esophagus was found by esophagectomy and pathological
      examination.

PMID- 14717421
TI  - One and a half ventricle repair for Ebstein's anomaly.
AB  - The surgical strategy for patients having Ebstein's anomaly and hypoplastic right
      ventricle is controversial. An 11-year-old boy patient having such condition,
      with estimated end-diastolic volume index of the atrialized and functional right
      ventricle being 70% of normally expected values, underwent biventricular repair.
      Immediately after the surgery, however, he developed right heart failure with the
      central venous pressure of 11 mmHg. He consequently underwent additional
      bidirectional cavopulmonary anastomosis, thereby converting the biventricular
      repair into one and a half ventricle repair. He recovered uneventfully and is
      doing well 2 years after the surgery.

PMID- 14717422
TI  - Lymphatic cardiac tamponade after open-heart surgery with liver dysfunction.
AB  - A 46-year-old female with alcoholic liver dysfunction was admitted for mitral
      regurgitation due to infective endocarditis. She underwent mitral valvuloplasty
      and resection of the vegetation without complication. After removal of the chest
      tube, late cardiac tamponade occurred and subsequently recurred. On the 64th day
      after mitral valvuloplasty, we performed redo median sternotomy with small
      laparotomy trying to reveal and repair injured lymphatic vessels in the
      pericardial space and successfully cured the leakage of lymph. The post
      reoperative course was uneventful and the patient was discharged 20 days after
      reoperation. We review a rare complication of recurrent cardiac tamponade of
      lymphatic leakage associated with liver dysfunction.

PMID- 14717423
TI  - Implantation of collar-reinforced sumit valve for patient with large calcified
      mass obstructing the mitral valve orifice.
AB  - A 56-year-old female had a severely calcified mitral valve annulus and a huge
      subvalvular mass. To avoid critical damages of the coronary artery and left
      ventricle, the annular calcification and the part of the mass adherent to the
      left ventricle were not resected. Then we performed mitral valve replacement
      using SuMit valve and collared reinforcement technique with xenopericardium
      without any major complications. The SuMit valve is designed to be placed in a
      supraannular position, and is useful to prevent valves from getting stuck.

PMID- 14717424
TI  - Progressive diffuse aortic stenosis after localized supravalvular aortic stenosis
      repair.
AB  - A 6-year-old boy presented with diffuse stenosis of the aortic arch. He had
      undergone patch augmentation for localized supravalvular aortic stenosis at 2
      years of age. Before the initial operation, the aortic arch and descending aorta
      were noticed to be hypoplastic with a diameter of 60 to 73% of that of the aortic
      annulus, without a pressure gradient. 4 years later, progressive diffuse stenosis
      of the aortic arch with a diameter of 42% of that of the aortic annulus was
      found. Reoperation, consisting of patch augmentation of the aortic arch, was
      carried out. A pressure gradient of 40 mmHg distal to the repair was newly
      recognized, again. This is a rare case of supravalvular aortic stenosis, which
      required reoperation because of the progression of diffuse stenosis of the distal
      aorta.

PMID- 14717425
TI  - Off-pump coronary artery bypass grafting in two renal transplant patients.
AB  - Coronary artery disease is a critical problem for a renal transplant patient.
      This paper reports off-pump coronary artery bypass grafting (OPCABG) in two cases
      after renal transplantation. The first, a 65-year-old woman, experienced chest
      pain 5 years after a renal transplantation. Coronary angiography (CAG) revealed
      stenosis of the left anterior descending artery (LAD) and the first diagonal
      artery (DB1). OPCABG [left internal thoracic artery (LITA) to DB1 and LAD] was
      performed. The second, a 67-year-old man, underwent percutaneous coronary
      intervention in the LAD 10 years ago. He experienced chest pain 2 years after a
      renal transplantation. CAG revealed restenosis of LAD. OPCABG (LITA to LAD) was
      performed. The patients' postoperative course was uneventful. OPCABG for a renal
      transplant patient was safe and useful since it is a less invasive procedure and
      easily managed perioperatively.

PMID- 14717426
TI  - Prosthetic valve endocarditis with extensive aortic root abscess: full aortic
      root reconstruction with stentless bioprosthesis, xenopericardium and mitral
      valve replacement.
AB  - Prosthetic valve endocarditis with an extensive aortic root abscess usually has
      high mortality and morbidity. A 71-year-old male with an extended aortic root
      abscess following aortic valve replacement survived after full aortic root
      reconstruction with glutaraldehyde bovine pericardium, mitral valve replacement
      and full root replacement using stentless bioprosthesis. The patient is well
      without recurrence of infection, 18 months postoperatively. This procedure might
      be an alternative treatment for prosthetic valve endocarditis with an extended
      aortic root abscess.

PMID- 14717427
TI  - Aortic valve replacement for a patient with porcelain aorta and retrosternal
      gastric tube reconstruction after esophageal resection.
AB  - A 67-year-old woman with congestive heart failure due to aortic stenosis and
      regurgitation needed aortic valve replacement. She had undergone right radical
      mastectomy 23 years before, and total thoracic esophagectomy with retrosternal
      gastric tube reconstruction 11 years before. Plain computed tomography showed
      coincident porcelain aorta. Aortic valve replacement was performed through a
      median sternotomy approach. Blunt dissection on anterior and right side of the
      gastric tube could be done with minimal injury, and the heart was exposed as in
      usual cardiac surgery. Preoperative multi-detector computed tomography revealed
      inhomogeneous and patchy distribution of calcification in the ascending aorta,
      and was helpful to decide aortotomy site. Aortic valve replacement was done and
      aortotomy was closed with felt strip buttressed running suture. Postoperative
      course was uneventful.

PMID- 14717428
TI  - Vascular ring in an extremely low birth weight infant.
AB  - Vascular rings due to aortic arch anomalies can be a major cause of
      tracheoesophageal obstruction in infants. But there is no report of vascular ring
      in an extremely low birth weight (ELBW) infant. This is a report of an infant
      with birth weight of 560 g, who has not diagnosed vascular ring until 6 months of
      age because of asymptomatic process by prolonged tracheal intubation. The patient
      was treated for double aortic arch with tracheomalacia surgically by simple
      division of the atretic left arch and the ligamentum arteriosus, aortopexy and
      tracheostomy before reaching full recovery at 3 years of age. We reported our
      management of vascular rings in the ELBW infant. This case suggested that the
      difficulty of extubation in ELBW infants in spite of the improvement of
      respiratory condition should raise a suspicion of the tracheal compression by
      other lesions such as vascular rings.

PMID- 14717429
TI  - Primary malignant schwannoma of the lung.
AB  - A 72-year-old male referred for surgical treatment underwent chest computed
      tomography to further investigate a well defined mass with a maximal diameter of
      3.2 cm at the left S10. There was no pathological diagnosis established by either
      bronchoscopic biopsy specimens or computed tomography-guided percutaneous needle
      biopsy. The lower lobe and mediastinal lymph nodes were excised (complete
      resection). The 6.5-cm encapsulated grayish mass showed extensive areas of
      hemorrhage and necrosis on cut surface. Results from histological and
      immunohistochemical study yielded a definitive diagnosis of malignant schwannoma.
      Primary malignant schwannomas of the lung are extremely rare and the prognosis is
      poor in most cases. Our patient is currently well without recurrence more than 2
      years after complete resection. Complete surgical resection is the best
      therapeutic option for primary malignant schwannoma of the lung.

PMID- 14717430
TI  - Delayed blow-out type rupture of the right ventricle following blunt chest
      trauma.
AB  - A 36-year-old man suffered multiple traumatic injuries when he fell from a crane.
      Fractures of both lower extremities, a compression fracture of the fourth lumbar
      vertebra, and bilateral hemopneumothoraxes were identified. The sternum was not
      fractured, but was tender. The day after admission, the right ventricular free
      wall ruptured and was diagnosed by echocardiography. An emergency operation was
      performed. A Gore-tex sheet was sutured from inside the ventricle, and a
      Hemashield graft was sutured over the tear. The risk of hemorrhage is high in the
      patient with multiple traumatic injuries when heparin is required. Mechanical
      ventilation was required until the 13th postoperative day because persistent
      hemothorax. After an operation to reduce a leg fracture, the patient was
      discharged from the hospital on the 66th postoperative day.

PMID- 14717431
TI  - Thoracic and cardiovascular surgery in Japan during 2001: annual report by the
      Japanese Association for Thoracic Surgery.

PMID- 14717432
TI  - Nitrogen use efficiency by a slow-growing species as affected by CO2 levels, root
      temperature, N source and availability.
AB  - This study examines the importance of N source and concentration on plant
      response to distinct CO2 concentrations and root temperatures. The experimental
      design of this work was a factorial combination of: CO2 concentration, nitrogen
      concentration, nitrogen source and root temperature. Carob (Ceratonia siliqua L.)
      was assessed as a potential model of a slow growing Mediterranean species. The
      results showed that: 1) biomass increment under high CO2 varied between 13 and
      100% in relation to plants grown under the same conditions but at ambient CO2
      concentrations, depending on the root temperature and nitrogen source; 2) nitrate
      fed plants attained a larger increase in biomass production compared to ammonium
      fed ones. This performance seems to be linked to the co-ordinated regulation of
      the activities of glutamine synthetase and sucrose phosphate synthase. The
      variations in the magnitude and nature of growth responses to elevated CO2
      observed resulted in substantial changes in the chemical composition of the plant
      material and consequently in plant nitrogen use efficiency. Although performed
      with seedlings and under controlled conditions, this work emphasizes the
      importance of the nitrogen source used by the plants, a factor rarely taken into
      consideration when forecasting plant responses to global changes. Particularly,
      the results presented here, highlight the potential for uncoupling biomass
      accumulation from increment of air CO2 concentration and show that more than
      nitrogen availability N source may offset positive plant growth responses under
      elevated CO2 and root temperature.

PMID- 14717433
TI  - Effects of 15N application frequency on nitrogen uptake efficiency in citrus
      trees.
AB  - Two irrigation systems were used to compare nitrogen uptake efficiency in citrus
      trees and to evaluate the NO3- runoff in "Navelina" orange trees [Citrus sinensis
      (L.) Osbeck] on Carrizo citrange rootstock (Citrus sinensis x Poncirus trifoliata
      Raf.). These were fertilized with 125 g N as labelled K15NO3 and grown outdoors
      in containers filled with a sand-loamy soil. Two groups of 3 trees received this
      N dose either in five equally split applications by a flooding irrigation system
      or in 66 applications by drip. Trees were harvested at the end of the vegetative
      cycle (December) and the isotopic ratios of 15N/14N were measured in the soil
      plant system. The N uptake efficiency of the whole tree was higher with drip
      irrigation (75%) than with flooding system (64%). In the 0-90 cm soil profile,
      the N immobilized in the organic fraction was similar for both irrigation methods
      (around 13 %), whereas the N retained as NO3- was 1% of the N applied under drip
      and 10% under flooding. In the last case, most of NO3- remained under root system
      and it could be lost to leaching either by heavy rainfalls or excessive water
      applications. These results showed that a drip irrigation system was more
      efficient for improving water use and N uptake from fertilizer, in addition to
      potentially reduced leaching losses.

PMID- 14717434
TI  - Tree size and flowering intensity as affected by nitrogen fertilization in non
      bearing orange trees grown under Mediterranean conditions.
AB  - 'Lane Late' orange trees. Five nitrogen (N) rates were used in a randomised block
      design with three replicates. The 180 g N tree(-1) over three years led to the
      greatest canopy width (176 cm) and volume (2,697 dm3). The greatest rate applied
      (720 g N tree(-1) in the three years) led to the largest flower yield. Nitrogen
      concentration in the flowers significantly increased with fertilizer N, and also
      with the flowering period up to the 23rd day, declining thereafter. Flower yield
      was strongly correlated (r = 0.99, p < 0.001) with flower N concentration.
      Nutrient composition of flowers and of mature leaves from the spring flush was
      compared. Significant correlations were found for N (r = 0.47, p < 0.01), P (r = 
      0.49, p < 0.01), K (r = 0.44, p < 0.05) and Ca (r = 0.87, p < 0.001), suggesting
      that flowers can be used as a tool to diagnose the nutritional status of trees.
      Canonical analysis (with N treatment as dummy-variables) showed strong
      relationships between canopy width and N, which were greater at the larger rates
      of fertilizer application, and strong and inverse relationships between K and Mg,
      also with the greatest N rates.

PMID- 14717435
TI  - Effects of foliar sprays containing calcium, magnesium and titanium on plum
      (Prunus domestica L.) fruit quality.
AB  - An experiment was performed in which Ti(4+)-ascorbate was sprayed onto plum trees
      in several combinations with other commercial compounds containing Ca2+ and Mg2+
      to study the effects on the commercial quality of fruits, with special focus on
      improving their resistance against postharvest handling damage. All the
      treatments containing titanium increased the tree performance (branch elongation,
      flowering and fruit setting intensities) and fruit size. At harvest fruits from
      the Ti-treated trees showed improved resistance to compression and penetration,
      as well as a decrease in weight-loss during postharvest storage. A similar
      response was obtained for the external colour, though all the treatments seemed
      to delay somewhat the apparent ripening status. Nevertheless, the fruits from Ti
      treated trees showed a better behaviour in the evolution of the colour parameters
      during storage than did the control fruits. Titanium application significantly
      increased the calcium, iron, copper and zinc concentrations in peel and flesh.
      This improvement in the calcium absorption is explained as a consequence of the
      beneficial effect of titanium on the absorption, translocation and assimilation
      processes.

PMID- 14717436
TI  - Study of aluminum toxicity by means of vital staining profiles in four cultivars
      of Phaseolus vulgaris L.
AB  - Aluminum toxicity is a very important factor limiting crop productivity on acid
      soils. Early effects of aluminum toxicity comprise inhibition of cell division
      and effects on root elongation. The plasma membrane can be the primary target of
      aluminum toxicity and thus, vital staining techniques could be a powerful tool in
      determining effects of metal stress on the plasma membrane. In this paper. we
      discuss the effects of Al on growth and membrane integrity by staining root tips
      with a mixture of fluorescein diacetate and propidium iodide. The results show a
      good correlation between results from growth measurement and the vital staining.
      From the comparison of the luminosity patterns generated by vital staining it is
      easy to determine Al-resistant varieties, revealing this technique as a powerful
      and fast method for determining tolerance to Al in different varieties.

PMID- 14717437
TI  - Influence of the Ca/Mg ratio on Cu resistance in three Silene armeria ecotypes
      adapted to calcareous soil or to different, Ni- or Cu-enriched, serpentine sites.
AB  - This hydroponic study addresses the influence of low (0.3) and high (4.0) Ca/Mg
      molar ratios on Cu resistance of Silene armeria ecotypes from different habitats:
      a calcareous soil (ecotype Cadriano), a Ni-rich serpentine site (ecotype
      Prinzera), and an acid Cu-mine spoil soil containing serpentinite (ecotype
      Vigonzano). Under control conditions, without excess Cu, only Cadriano was
      negatively affected by the low Ca/Mg ratio. Under both low and high Ca/Mg ratios
      Cu resistance followed the order Vigonzano more more than Prinzera > Cadriano.
      More efficient Cu exclusion accounted for enhanced Cu resistance in Prinzera. The
      low Ca/Mg ratio increased Cu uptake in Prinzera but did not worsen toxicity
      effects; i.e. the plants had higher internal Cu effect concentrations. In
      Vigonzano Cu resistance was enhanced by the low Ca/Mg ratio. This was due only in
      part to better Cu exclusion. Magnesium-induced tolerance to higher Cu tissue
      concentrations appears to be in ecotypes from serpentine and acid mine spoils,
      but not in plants from calcareous soil, the exposure to low Ca/Mg ratio favours
      internal detoxification of Cu by means of more efficient chelation and
      compartmentation.

PMID- 14717438
TI  - Accumulating behaviour of Lupinus albus L. growing in a normal and a decalcified
      calcic luvisol polluted with Zn.
AB  - Lupinus albus L. is a leguminous plant that is starting to generate interest for
      the phytoremediation soils showing intermediate metal pollution. Among these
      metals, Zn causes major phytotoxicity problems and is common in polluted soils of
      central Spain. The purpose of this study was to explore the nutritional behaviour
      of this plant species towards increasing Zn concentrations in two calcic luvisol
      soils: a normal basic soil and a decalcified acid soil. For this purpose the
      effects of different Zn concentrations on mineral nutrition, growth, nodulation
      and nitrogenase activity of nodulated Lupinus albus cv. Multolupa plants has been
      investigated. A 12-week trial was performed in pots under greenhouse conditions.
      In each soil, four replicate pots were set up per treatment (100, 150, 300, 500
      and 700 ppm Zn). Seeds were inoculated with a Bradyrhizobium sp. (Lupinus) strain
      ISLU-16. Statistical analysis of data revealed significant effects of soil Zn on
      grown, plant mineral composition and nodulation. Lupin growth was better in acid
      soil than in basic soil with the low dose of Zn applied, although plant growth in
      acid soil was severely affected from 300 ppm Zn, where the pH of the soil was
      4.7. Zn application produce nutritional imbalances, especially with the higher
      dose added. Most of Zn accumulation occurred in the roots in both types of soils.
      In acid soil, lupin absorbs high amounts of Zn in both root (4650 ppm) and aerial
      part (3605 ppm), when the doses of Zn applied was 300 ppm. This feature permits
      Lupinus albus cv. Multolupa to be considered as potential phytoremediator and
      also for the revegetation of degraded landfill areas with slightly acid or
      neutral soils polluted with Zn.

PMID- 14717439
TI  - Selection of olive varieties for tolerance to iron chlorosis.
AB  - Under certain conditions, olive trees grown on calcareous soils suffer from iron
      chlorosis. In the present study several olive varieties and scion-rootstock
      combinations were evaluated for their tolerance to iron chlorosis. Plants were
      grown over several months in pots with a calcareous soil, under two fertilization
      treatments. These consisted of periodic applications of nutrient solutions
      containing either, 30 micromol/L FeEDDHA or not Fe. Tolerance was assessed by the
      chlorosis and growth parameters of plants grown without Fe, compared to those
      plants grown with Fe. Results show that there are differences in tolerance among
      olive varieties and that tolerance is mainly determined by the genotype of the
      rootstock. These results open the way to use tolerant varieties for those
      conditions where iron chlorosis could become a problem.

PMID- 14717440
TI  - Effects of branch solid Fe sulphate implants on xylem sap composition in field
      grown peach and pear: changes in Fe, organic anions and pH.
AB  - The effects of placing solid implants containing Fe sulfate in branches of Fe
      deficient pear and peach trees on the composition of the xylem sap have been
      studied. Iron sulfate implants are commercially used in northeastern Spain to
      control iron chlorosis in fruit trees. Implants increased Fe concentrations and
      decreased organic acid concentrations in the xylem sap, whereas xylem sap pH was
      only moderately changed. The citrate to Fe ratios decreased markedly after
      implants, therefore improving the possibility that Fe could be reduced by the
      leaf plasma membrane enzyme reductase, known to be inhibited by high citrate/Fe
      ratios. In peach, the effects of the implants could be observed many months post
      treatment. In pear, some effects were still observed one year after the implants
      had taken place. Results obtained indicate that solid Fe sulfate implants were
      capable of significantly changing the chemical composition of the xylem sap in
      fruit trees.

PMID- 14717441
TI  - Plastocyanin/cytochrome c6 interchange in Scenedesmus vacuolatus.
AB  - Plastocyanin and cytochrome c6 from the green alga Scenedesmus vacuolatus were
      immunoquantified in cells grown under different concentrations of copper and
      iron. Plastocyanin expression was constitutive, its synthesis was not
      significantly affected by iron availability, and increases with copper
      availability. On the contrary, cytochrome c6 synthesis is repressed by copper,
      and only residual amounts of the protein were detected at 0.1 micromol/L copper.
      Under copper deficiency, cytochrome c6 is slightly dependent on iron. In natural
      environments, plastocyanin seems to be the predominant electron donor to P700.

PMID- 14717442
TI  - Different blocking effects of HgCl2 and NaCl on aquaporins of pepper plants.
AB  - In this study we have compared the short-term effects of both NaCl and HgCl2 on
      aquaporins of Capsicum annuum L. plants, in order to determine whether or not
      they are similar. Stomatal conductance, turgor, root hydraulic conductance and
      water status were measured after 0.5, 2, 4 and 6 h of NaCl (60 mmol/L) or HgCl2
      (50 micromol/L) treatment. When 60 mmol/L NaCl was added to the nutrient
      solution, a large decrease in stomatal conductance was observed after 2 h.
      However, when HgCl2 (50 micromol/L) was added, the decrease occurred after 4 h.
      The number of open stomata closed was always lower in plants treated with HgCl2
      than in plants treated with NaCl. The water content of the Hg(2+)-treated plants
      was decreased, compared with controls and NaCl-treated. The root hydraulic
      conductance decreased after HgCl2 and NaCl treatment plants. Turgor of leaf
      epidermal cells was greatly reduced in plants treated with HgCl2, but remained
      constant in the NaCl treatment, compared with control plants. The fact that the
      stomatal conductance was reduced more rapidly after NaCl addition, followed by
      the stomatal closure, and that both water content and turgor did not differ from
      the control suggests that in NaCl-treated plants there must be a signal moving
      from root to shoot. Therefore, the control of plant homeostasis through a
      combined regulation of root and stomatal exchanges may be dependent on aquaporin
      regulation.

PMID- 14717443
TI  - Recovery of development and functionality of nodules and plant growth in salt
      stressed Pisum sativum--Rhizobium leguminosarum symbiosis by boron and calcium.
AB  - Nodules developed in Pisum sativum L. cv. Argona inoculated with Rhizobium
      leguminosarum bv. viciae 3841 and growing under saline conditions (75 mmol/L
      NaCl) are non functional and had abnormal structure. The infected cells contained
      a low amount of endophytic bacteria, compared to treatments without salt.
      Addition of B (up to 55.8 micromol/L) and Ca2+ (up to 2.72 mmol/L) increased
      bacterial population of host plant cells in salt-stressed nodules. Furthermore,
      symbiosomes developed inside the nodules from salt treated plants presented a
      degraded peribacteroid membrane. This effect was also prevented by combined
      addition of B and Ca2+. Given the importance of both nutrients in cell wall
      structure, the pectin fraction was studied by electron microscopy and
      immunological methods. Salt stress produced cells with walls dramatically altered
      or even degraded in several zones. Pectin polysaccharides, detected by JIM 5
      monoclonal antibody, increased in cells under salinity. These effects resembled
      typical effects of B-deficiency reactions in cell walls, and the increase of both
      Ca2+ and especially B also prevented these alterations.

PMID- 14717444
TI  - Fluorescence induction of Photosystem II membranes shows the steps till reduction
      and protonation of the quinone pool.
AB  - Chlorophyll fluorescence induction (Chl-F) was investigated in Photosystem II
      (PSII)-enriched membranes, which predominantly include active (QB reducing) PSII
      reaction centres (RCs) and lack Photosystem I (PSI). The Chl-F curve of these
      preparations show a polyphasic rise from F0, the minimal fluorescence, to FP, the
      maximal fluorescence, with several intermediate transitions. Analyses of these
      transitions revealed three exponential rise components with lifetimes of 18 ms,
      400 ms and 800 ms. The 18 ms component was assigned to the photoaccumulation of
      reduced QA. The two slowest components, of 400 ms and 800 ms, were assigned to QB
      reduction (QB- and QB =) and further QB= protonation (till QBH2), respectively.
      These assignments were based on the observation of specific quenching of the
      phases by DCMU or by different oxidized, reduced and protonated quinones. The
      work is done in low light conditions which are saturating to avoid
      photoinhibition or PSII inactivation effects. The results suggest that the Chl-F
      curve observed in PSII-enriched membranes can be attributed to the sequential
      steps till the photoaccumulation (reduction and protonation) of plastoquinone
      (PQ) by PSII. These results are in good agreement with the molecular models that
      show a correspondence between Chl-F and PQ reduction steps, like the models that
      propose and explain the O-J-I-P transients.

PMID- 14717445
TI  - Peroxisomes from pepper fruits (Capsicum annuum L.): purification,
      characterisation and antioxidant activity.
AB  - Pepper is a vegetable of importance in human nutrition. Currently, one of the
      most interesting properties of natural products is their antioxidant content. In
      this work, the purification and characterisation of peroxisomes from fruits of a
      higher plant was carried out, and their antioxidative enzymatic and non-enzymatic
      content was investigated. Green and red pepper fruits (Capsicum annuum L., type
      Lamuyo) were used in this study. The analysis by electron microscopy showed that
      peroxisomes from both types of fruits contained crystalline cores which varied in
      shape and size, and the presence of chloroplasts and chromoplasts in green and
      red pepper fruits, respectively, was confirmed. Peroxisomes were purified by
      differential and sucrose density-gradient centrifugations. In the peroxisomal
      fractions, the activity of the photorespiration, beta-oxidation and glyoxylate
      cycle enzymes, and the ROS-related enzymes catalase, superoxide dismutase,
      xanthine oxidase, glutathione reductase and NADP(+)-dehydrogenases, was
      determined. Most enzymes studied had higher specific activity and protein content
      in green than in red fruits. By native PAGE and western blot analysis, the
      localisation of a Mn-SOD in fruit peroxisomes was demonstrated. The ascorbate and
      glutathione levels were also determined in crude extracts and in peroxisomes
      purified from both green and red peppers. The total ascorbate content (200-220 mg
      per 100 g FW) was similar in crude extracts from the two types of fruits, but
      higher in peroxisomes from red peppers. The glutathione concentration was 2-fold
      greater in green pepper crude extracts than in red fruits, whereas peroxisomes
      from both tissues showed similar values. The presence in pepper peroxisomes of
      different antioxidative enzymes and their corresponding metabolites implies that
      these organelles might be an important pool of antioxidants in fruit cells, where
      these enzymes could also act as modulators of signal molecules (O2*-, H202)
      during fruit maturation.

PMID- 14717446
TI  - Dicyandiamide and 3,4-dimethyl pyrazole phosphate decrease N2O emissions from
      grassland but dicyandiamide produces deleterious effects in clover.
AB  - The application of nitrogen fertilisers leads to different ecological problems
      such as nitrate leaching and the release of nitrogenous gases. N2O is a gas
      involved in global warming, therefore, agricultural soils can be regarded as a
      source of global warming. Soil N2O production comes from both the nitrification
      and denitrification processes. From an ecological viewpoint, using nitrification
      inhibitors with ammonium based fertilisers may be a potential management strategy
      to lower the fluxes of N2O, thus decreasing its undesirable effect. In this
      study, the nitrification inhibitors (NIs) dicyandiamide (DCD) and 3,4-dimethyl
      pyrazole phosphate (DMPP) have been evaluated as management tools to mitigate N2O
      emissions from mineral fertilisation and slurry application in grassland systems
      (experiments 1 and 2), and to assess the phytotoxic effect of these inhibitors
      per se on clover (experiment 3). Both nitrification inhibitors acted in
      maintaining soil nitrogen (N) in ammonium form, decreasing cumulative N2O
      emissions. DCD, but not DMPP, produced phytotoxic effects and yield reduction in
      white clover. A nutrient imbalance, which led to a senescence process visually
      observed as chlorosis and necrosis at the border of the leaves, was noted.

PMID- 14717447
TI  - Efficiency of procedures for induction and cultivation of Pseudomonas syringae
      pv. pisi L-form.
AB  - The L-form of Pseudomonas syringae pv. phaseolicola has been proved to induce
      resistance to bean halo blight. Various procedures were tested to induce the L
      form of Pseudomonas syringae pv. pisi for its potential use as biocontrol agent
      of pea bacterial blight. Cell-wall deficient cells were induced in a liquid
      medium with penicillin following a protocol described for P. s. pv. phaseolicola.
      Cell growth on solid induction medium developed as typical granular and
      vacuolated structures, and characteristic colonies were observed in the first
      transfer. However, there was poor growth in subsequent transfers and some
      reversion to the parental type. To improve the induction procedure, the following
      new procedures were applied: (1) viability of cells was monitored during
      induction. The optimum induction time in liquid medium with penicillin was lower
      for pv. pisi than for pv. phaseolicola. Viability of L-forms in solid induction
      medium with penicillin was low and decreased in time. (2) the inducer ticarcillin
      was combined with clavulanic acid, which prevented the reversion to the parental
      type and (3) a range of concentrations of penicillin and ticarcillin/clavulanic
      acid was applied by the spiral gradient endpoint method for calculation of
      minimum inhibitory concentrations (MIC). Based on the results from these tests an
      induction method for P. s. pv. pisi L-form is proposed and the relevance of L
      form is discussed for practice.

PMID- 14717448
TI  - Assessment of the antibacterial activity of selected flavonoids and consideration
      of discrepancies between previous reports.
AB  - Activity of the flavonoids apigenin, baicalin and galangin against sensitive and
      antibiotic resistant strains of Staphylococculs aureus, Enterococcus faecalis, E.
      faecium, Escherichia coli and Pseudomonas aeruginosa was investigated. Using an
      agar dilution assay, galangin was shown to have a minimum inhibitory
      concentration (MIC) of 25 to 50 microg/mL against all six strains of S. aureus
      but negligible activity against the othe species. Apigenin displayed only
      marginal activity against S. aureus and no activity was detected from baicalin.
      In inhibition curve studies, galangin caused a 100,000-fold decrease in the
      viability of a growing population of S. aureus NCTC 6571 within the first two
      hours of treatment. Decreases in viability of S. aureus NCTC 11561 and NCIMB 9968
      populations were also observed.

PMID- 14717449
TI  - Diversity of culturable phyllosphere bacteria on beech and oak: the effects of
      lepidopterous larvae.
AB  - The community composition of epiphytic heterotrophic bacteria on leaves of beech
      and oak, which were either damaged by lepidopterous larvae or remained undamaged,
      was investigated. In addition, the ability of these bacteria to utilize inorganic
      nitrogen was studied. The bacteria were isolated on nutrient agar and
      systematically identified with biochemical and physiological tests. Rarefaction
      plots and the Shannon-Wiener function revealed that species diversity was
      significantly higher on leaves of damaged beech compared to undamaged leaves, but
      no differences were found on leaves of oak. The portion of bacterial isolates
      showing a strong response to ammonia and nitrate was significantly larger on
      leaves of oak than on those of beech. Furthermore, significantly more isolates
      with a high capability to assimilate both nitrogen compounds were found on leaves
      attacked by the folivorous larvae compared to those not attacked on oak. It is
      suggested that the changes in the microbial community in response to folivorous
      insects might affect the extent of nutrient cycling exceeding eventually the
      scale of a leaf.

PMID- 14717450
TI  - Abundance of potentially pathogenic micro-organisms in Penaeus monodon larvae
      rearing systems in India.
AB  - Monodon baculovirls (MBV), external fouling organisms (EFO) and bacteria
      (especially Vibrio species) were monitored during 1996-1997 at nine different
      Penaeus monodon rearing hatcheries in India. Total cultivable heterotrophic
      bacteria, Vibrio-like-bacteria, presumptive Vibrio harveyi, Vibrio anguillarum,
      Vibrio vulnificus counts were determined from shrimp eggs, post larvae, rearing
      tank water, source sea water, feed (Artemia nauplii and microencapsulated feed).
      The MBV infected post larvae and their environment showed higher Vibrio-like
      bacteria than uninfected post larvae. An overwhelming predominance of presumptive
      Vibrio harveyi and Vibrio anguillarum was observed in post larval rearing tank
      water, MBV infected and uninfected post larvae. Vibrio-like-bacteria in Artemia
      nauplii clearly showed the possible source of these pathogenic bacteria in the
      hatchery environments. Quantitative analysis of Vibrio-like-bacteria in
      hatcheries revealed that when the Vibrio-like-bacteria increases to 2 x 10(2) CFU
      mortality of the post larvae occurs. Abundance of these micro-organisms in
      hatchery samples indicated that they are opportunistic pathogens which can invade
      the shrimp tissue, subsequently cause disease when the post larvae were under
      stressful conditions.

PMID- 14717451
TI  - During stationary phase, Beijerinckia derxii shows nitrogenase activity
      concomitant with the release and accumulation of nitrogenated substances.
AB  - Beijerinckia derxii, a free-living nitrogen-fixing bacterium, maintained an
      increasing nitrogenase specific activity during the stationary growth phase. To
      verify the destination of the nitrogen fixed during this phase, intra and
      extracellular nitrogenated contents were analyzed. Organic nitrogen and amino
      acids were detected in the supernatant of the cultures. An increase in
      intracellular content of both nitrogen and protein occurred. Cytoplasmic granules
      indicated the presence of arginine. The ability of a non-diazotrophic bacterium
      (E. coli) to use B. derxii proteins as a source of nitrogen was observed
      concomitantly with E. coli growth. There is a suggestion that B. derxii
      contributes to the environment by both releasing nitrogenated substances and
      accumulating substances capable of being consumed after its death.

PMID- 14717452
TI  - Membrane vesicles in magnetotactic bacteria.
AB  - Magnetotactic bacteria are microorganisms that respond to magnetic fields. We
      have studied the surface ultrastructure of Magnetospirillum magnetotacticum and
      uncultured magnetotactic bacteria from a marine environment using transmission
      electron microscopy and freeze-etching. Numerous membrane vesicles were observed
      on the surface of Magnetospirillum magnetotacticum bacteria. All uncultured
      magnetotactic bacteria presented membrane vesicles on their surface in addition
      to an extensive capsular material and an S-layer formed by particles arranged in
      a hexagonal symmetry. We did not observe any indication of electron-dense
      precipitation on the surface of these microorganisms. Our results indicate that
      membrane vesicles are a common characteristic of magnetotactic bacteria in
      natural sediments.

PMID- 14717453
TI  - Growth inhibition of a phytopathogenic fungus, Colletotrichum species by acetic
      acid.
AB  - Acetic, oxalic, malic, and citric acids significantly inhibited the growth of
      Colletotrichurm, gloeosporioides, a phytopathogenic fungus, and acetic acid
      showed the strongest inhibition with no growth at 50 mM. The growth inhibition by
      these organic acids was closely related with the inhibition of respiration, as
      tested using three species, C. gloeosporioides, C. coccodes, and C. dermatium.
      Optimum growth of C. gloeosporioides was observed around pH 6.0. The inhibition
      of growth by acetic acid accelerated along with a decrease in pH from 6.0 to 4.0,
      suggesting that the inhibition might be more enhanced by undissociated form of
      acetic acid. Despite of growth inhibition by acetic acid, the fungus was able to
      grow in a normal medium when acetic acid was eliminated, implying that the growth
      inhibition may be resulted from an acetic acid-mediated inhibition of respiration
      than a structural damage of cell. Catalase activity of the fungus increased in
      response to 0.1% hydrogen peroxide, but addition of this together with 30 mM
      acetic acid brought about a decrease in the activity. The fungus which showed no
      grow at 30 mM acetic acid or 0.5% hydrogen peroxide began to grow after the
      elimination of these. But the fungus added simultaneously by these two compounds
      did not grow at all despite the elimination of these. Thus, controlling of
      Colletotrichum might be developed using acetic acid which is generally less
      dangerous than chemical reagents.

PMID- 14717454
TI  - Development and morphological features of biofilms formed by transgenic and wild
      type strains of Bacillus subtilis.
AB  - The study addressed the ability of the transgenic strain (TM) B. subtilis
      2335/pBMB 105 (KmrInf+) to form biofilms on the surface of liquid media of
      various compositions, inoculated with vegetative cells and spores. The
      morphological features of these biofilms do not differ from those of the films
      formed by the recipient strain (WT) B. subtilis 2335 (Kms). However. the TM and
      the natural one differ in the dynamics of biofilm formation and the cellular
      composition of the films. Biofilms of the TM are formed earlier, develop at a
      higher rate, but decompose later than the films of the WT. When the medium is
      inoculated with vegetative cells, sporulation in the biofilms of both strains
      undergoes glucose repression; no such effect is observed when the medium is
      inoculated with spores. The TM does not form films when the medium is inoculated
      with spores and supplemented with glycerin and kanamycin.

PMID- 14717455
TI  - Molecular analysis of a perchlorate reductase from a perchlorate-respiring
      bacterium Perc1ace.
AB  - Perchlorate (ClO4-) is a major ground water pollutant of public health concern.
      ClO4- reductase is the key enzyme in the pathway of ClO4- breakdown. ClO4-
      reductase from cell-free extracts of the ClO4- -respiring bacterium perc lace was
      purified 10-fold by ion-exchange and molecular exclusion fast protein liquid
      chromatography (FPLC). The ClO4- reductase catalyzed the reduction of ClO4- at a
      Vmax and Km of 4.8 U mg protein(-1) and 34.5 microM, respectively. ClO4-
      reduction was achieved in the temperature range of 20 to 40 degrees C and with
      optimum activity at 25 degrees C to 30 degrees C and pH 7.5 to 8.0. Molecular
      masses of two subunits of ClO4- reductase were determined by SDS-PAGE to be 35
      kDa and 75 kDa. MALDI-TOF/MS analysis of a trypsin digest of the 35 kDa subunit,
      revealed several tryptic peptides. Amino acid sequences of 22 tryptic peptides of
      the 35 kDa ClO4- reductase subunit were obtained by electrospray mass
      spectrometry. GenBank protein Blast analysis of the amino acid sequences revealed
      relevant similarity to reductases, dehydrogenases and heme proteins. Data
      obtained are useful towards the identification of the overall genetic
      determinants of ClO4- reduction and specific in situ detection of ClO4- as well
      as NO3-reducing bacteria in ground water.

PMID- 14717456
TI  - Intracellular phosphorus metabolism of Microcystis aeruginosa under various redox
      potential in darkness.
AB  - Phosphorus metabolism of Microcystis aeruginosa was studied under gradient redox
      potential from 252 mV to -70 mV in darkness. The release of phosphorus occurred
      in all the treatments, and this process was accelerated in darkness when the
      redox potential was lowered. Low redox potential in darkness stimulated the
      accumulation of polyphosphate (PolyP) and the degradation of polyglucose. The
      synthesis of PolyP delayed the decrease of intracellular orthophosphate. The
      death of M. aeruginosa was slowered when the redox potential was low in darkness.
      The accumulation of PolyP under low redox potential in the dark was very
      important to M. aeruginosa for endurance through the unfavorable growth
      conditions for maintaining phosphorus concentration, energy storage, and other
      physiological functions. The ability to accumulate PolyP in the dark and negative
      redox potential may be of considerable advantage in the low-light, organically
      rich, and low-redox habitats.

PMID- 14717457
TI  - In vitro antimicrobial activity of propolis and synergism between propolis and
      antimicrobial drugs.
AB  - The aim of this study was to investigate antimicrobial properties of ethanolic
      extract of 13 propolis (EEP) samples from different regions of Serbia against 39
      microorganisms (14 resistant or multiresistant to antibiotics), and to determine
      synergistic activity between antimicrobials and propolis. Antimicrobial activity
      of propolis samples was evaluated by agar diffusion and agar dilution method. The
      synergistic action of propolis with antimicrobial drugs was assayed by the disc
      diffusion method on agar containing subinhibitory concentrations of propolis.
      Obtained results indicate that EEP, irrespectively of microbial resistance to
      antibiotics, showed significant antimicrobial activities against Gram-positive
      bacteria (MIC 0.078%-1.25% of EEP) and yeasts (0.16%-1.25%), while Gram-negative
      bacteria were less susceptible (1.25%-->5%). Enterococcus faecalis was the most
      resistant Gram-positive bacterium, Salmonella spp. the most resistant Gram
      negative bacteria, and Candida albicans the most resistant yeast. EEP showed
      synergism with selected antibiotics, and displayed ability to enhance the
      activities of antifungals. The shown antimicrobial potential of propolis alone or
      in combination with certain antibiotics and antifungals is of potential medical
      interest.

PMID- 14717458
TI  - 'P' solubilization potential of plant growth promoting Pseudomonas mutants at low
      temperature.
AB  - Pseudomonas fluorescens strain GRS1, PRS9 and their cold tolerant mutants were
      examined for their tricalcium phosphate (TCP) solubilizing activity in NBRIP
      (broth) media at 10 degrees C and 25 degrees C. Invariably, all the cold tolerant
      mutants of GRS1 and PRS9 were found more efficient than their respective wild
      type counterparts for 'P' solubilization activity at 10 degrees C as compared to
      25 degrees C. 'P' solubilization potential of CRM was found maximum among all the
      strains followed by CRPF6 and CRPF4. To the best of out knowledge, this is the
      first report regarding low temperature 'P' solubilization activity.

PMID- 14717459
TI  - Fluctuation of endophytic bacteria and phytoplasmosis in elm trees.
AB  - A total of 658 heterotrophic bacterial colonies isolated from phloem tissues of
      roots and branches in four months (April, June, September and December) from two
      elm plants, one of which affected by phytoplasmosis, were typed by means of
      ARDRA. This analysis revealed the existence of a high degree of variability
      within the community and was able to detect 84 different ARDRA groups. The
      Analysis of Molecular Variance was applied to ARDRA patterns to analyze the
      differentiation between communities isolated from the various samplings. Data
      obtained were compared with those from a previous work (Mocali et al. 2003).
      Results indicated that plants with symptoms of phytoplasmosis showed marked
      alterations in the extent of the fluctuations of the community along the seasons
      in the different plant organs.

PMID- 14717460
TI  - Assessing local market and organizational readiness for the integration of
      complementary and alternative medicine into ambulatory care centers.
AB  - Complementary and alternative medicine (CAM) is one of the fastest growing
      segments of the health care industry today, with studies suggesting that between
      30% and 50% of the adult population in the United States uses some form of CAM.
      Many ambulatory care centers are considering integrating CAM into their clinical
      services. This article will review some of the national trends and present a
      framework for assessing local market demand for CAM in order to help prioritize
      an organization's CAM integration strategy.

PMID- 14717461
TI  - Use of complementary and alternative medicine by the adult membership of a large
      northern California health maintenance organization, 1999.
AB  - Data from general health surveys completed by random samples of adult members of
      a large Northern California health maintenance organization in 1996 and 1999 were
      used to investigate (a) the prevalence of use of 15 complementary and alternative
      medicine (CAM) modalities by adult members in 1999, (b) how prevalence varied by
      age group and gender, and (c) which modalities were increasing in popularity.
      While Northern California is not representative of the nation as a whole, it
      tends to be a harbinger of trends to come. The most widely used modalities in
      1999 were herbal and other nonvitamin/nonmineral nutritional supplements,
      prayer/spiritual healing done by oneself, chiropractic, massage therapy, and mind
      body medicine modalities. However, use of the different modalities varied
      significantly by age and gender, and rates of use of nutritional supplements and
      the manipulatives were approximately doubled, when restricted to subpopulations
      at high risk, for use because of relevant health conditions. There appeared to be
      a statistically significant, but modest increase in CAM use, mostly due to a
      large increase in use of nutritional supplements. Implications for how CAM use
      should be tracked for ambulatory care populations and the importance of
      addressing nutritional supplement use in ambulatory clinical care are discussed.

PMID- 14717462
TI  - Mind-body medicine in ambulatory care: an evidence-based assessment.
AB  - Ambulatory medicine is a frequent clinical setting where practitioners can
      effectively apply Mind-body interventions ranging from basic stress management
      therapies to the sophisticated biomedical instrumentation of clinical
      biofeedback. Given the rather extensive and growing body of clinical research in
      this area, the intent of this article is to provide an evidence-based assessment
      of the evidence underlying the clinical efficiency of such interventions. Such an
      evidence-based approach can help ambulatory care providers to identify those Mind
      body interventions with specific clinical indication so that they can be utilized
      both safely and effectively in ambulatory medicine.

PMID- 14717463
TI  - On the integration of complementary and conventional medicine within health
      maintenance organizations.
AB  - The integration of complementary and alternative medicine (CAM) with conventional
      medicine continues across practice settings and modalities. Managed care is of
      particular interest to practitioners, policy makers, and researchers concerned
      with the evolution of CAM integration. Within health maintenance organizations
      (HMOs), availability, coverage, and support of CAM are variable. We present an
      organizational model within which we identify factors that influence the degree
      of CAM integration within HMOs. We describe avenues through which CAM is
      currently available within the Northwest Region of Kaiser Permanente (KPNW). We
      also describe research methods applicable to the study of CAM integration within
      HMOs.

PMID- 14717464
TI  - Approaching complementary and alternative medicine use in patients with cancer:
      questions and challenges.
AB  - Complementary and alternative medicine (CAM) is becoming a significant factor in
      the arena of cancer care. There is an increasing body of research along with
      widespread popularity and use by patients with cancer. This article reviews
      current knowledge about the worldwide use of CAM in the treatment of cancer and
      patients' motives and reasoning for this use. Clinical research in CAM cancer
      treatments and physicians' attitudes toward this popular trend among patients
      with cancer are discussed as well. The physician-patient communication and its
      relevance to CAM use is emphasized. A step approach is suggested for primary care
      physicians including the discussion of CAM in the management of cancer in order
      to enrich the physician-patient dialogue and improve the quality of the clinical
      encounter.

PMID- 14717465
TI  - A clinician's commentary on Veterans Health Study: it's a jungle in here! The
      ecological web of disease, illness, and quality of life.

PMID- 14717466
TI  - Achievements of the Veterans Health Study.

PMID- 14717467
TI  - Commentary on the Veterans Health Study.

PMID- 14717468
TI  - Patient-reported measures of health: The Veterans Health Study.
AB  - The goal of the Veterans Health Study (VHS) was to extend the work of the Medical
      Outcomes Study (MOS) into the VA, by developing methodology for monitoring
      patient-based outcomes of care for use in ambulatory outpatient care. The
      principal objective of the VHS was developing valid and reliable measures to
      assess general health-related quality of life (HRQoL) and identifying the
      presence of selected health conditions, their severity, and their impact on
      HRQoL. In this article, we provide an overview of the historical context,
      framework, objectives, and applications of the VHS for the purpose of assessing
      the health outcomes of veteran patients. The VHS is a prospective observational
      study that has followed 2425 VA patients for up to 2 years. The patients were
      sampled from users of the Veterans Affairs (VA) ambulatory care system in the
      Boston area. The health conditions selected were hypertension, diabetes, chronic
      lung disease, osteoarthritis of the knee, chronic low-back pain, and alcohol
      related problems. These conditions were chosen because they are both prevalent in
      the VA and have measurable impacts on HRQoL. One of the cornerstones of the VHS
      was the development of the Veterans SF-36, modified from the MOS SF-36 for use in
      veteran ambulatory populations. Other key accomplishments included the
      development of patient-based disease-specific measures of health and the
      establishment of methods and logistics for comprehensive health outcomes research
      in large health care systems such as the VA, using these patient-based measures.
      Selected measures developed in the VHS, eg, the Veterans SF-36, have been
      integrated into the VA outcomes measurement system. The scope of the VHS is
      unique; it resulted in the development of a broad range of patient-focused
      process and outcome measures, as well as methodologies for assessing large
      numbers of patients, that have been widely used in the VA outpatient health care
      system for monitoring health outcomes across the nation.

PMID- 14717469
TI  - The right to equal treatment: ending racial and ethnic disparities in health
      care.

PMID- 14717470
TI  - Cardiovascular disease mortality.
AB  - Although mortality from cardiovascular diseases (CVDs) has been declining, it
      remains the leading cause of death among urban U.S. blacks. McCord and Freeman
      reported CVD as the major contributor to excess mortality in Central Harlem.
      However the disease-specific CVD mortality was not assessed. Thus, it was unclear
      what the distribution of specific CVDs was in Central Harlem and their
      contribution to excess mortality. We reviewed the vital statistics records of New
      York City (NYC) Department of Health for 1990 and identified all cases in which
      the cause of death was coded as cardiovascular (International Classification of
      Diseases-ICD, 9th Revision, codes 391, 393-398, 401-404, 410, 411, 414-417, 420
      438 and 440-444). The total and disease-specific CVD mortality for NYC and
      Central Harlem were calculated using the appropriate 1990 census data as the
      denominator. Central Harlem residents aged between 25-64 years were at least
      twice as likely to die from cardiovascular causes, compared to NYC residents.
      Hypertension-related deaths, ICD codes 401 (essential hypertension), 402
      (hypertensive heart disease), 403 (hypertensive renal disease), and 404
      (hypertensive heart and renal disease), were the major cause of excess death for
      men and women in Central Harlem. These findings show the importance of
      hypertension as the main determinant of the excess cardiovascular mortality in
      urban blacks and suggest an increased risk of cardiovascular death in blacks
      residing in Central Harlem.

PMID- 14717471
TI  - Nevirapine plus efavirenz plus didanosine: a simple, safe, and effective once
      daily regimen for patients with HIV infection.
AB  - Conventional highly active antiretroviral therapy (HAART) regimens used to treat
      human immunodeficiency virus (HIV) infection typically use nucleoside reverse
      transcriptase inhibitors (NRTIs) and either a protease inhibitor (PI) or a non
      nucleoside reverse transcriptase inhibitor (NNRTI). Because PI-based regimens are
      associated with significant long-term toxicity and adherence difficulty, there is
      a need for novel regimens that maximize combination treatment options. This 12
      month, observational, cohort study evaluated the efficacy, safety, and
      tolerability of a novel three-drug HAART regimen. Drug treatment consisted of
      nevirapine (NVP), efavirenz (EFV), and didanosine (ddl). Twenty-six treatment
      naive and -experienced HIV-1+ men and women were included in the study.
      Assessment consisted of CD4+ cell count, plasma HIV-1 RNA load, and adverse
      effects of study medications. After one year of therapy, 11/12 treatment-naive
      subjects (92%) and 8/9 treatment-experienced subjects (89%) had viral loads < 400
      copies/mL. Both groups also had an excellent immune response. At one year, there
      was a mean increase of 438 CD4+ cells/mm3 among treatment-naive subjects and 367
      cells/mm3 among treatment-experienced subjects. Treatment-limiting adverse
      effects occurred in 3/15 treatment-naive (20%) and 2/11 treatment-experienced
      (18%) subjects. These preliminary data suggest that the combination of NVP, EFV,
      and ddl is simple, safe, and effective.

PMID- 14717472
TI  - Predictors of hospital admissions in the elderly: analysis of data from the
      Longitudinal Study on Aging.
AB  - Healthcare for the elderly population presents enormous challenges, which are
      further complicated by ethnicity-related socioeconomic disparities in the United
      States. We set out to determine the predictors of hospital admissions in the
      elderly by conducting a retrospective cohort analysis of a nationally
      representative sample of community-dwelling individuals aged 70 and older in 1984
      (n = 7541). Multivariate logistic regression analysis of data from the
      Longitudinal Study on Aging revealed that race, health status, type of family
      relationship, and activities of daily living (ADL) are significant predictors of
      hospitalization among the elderly. Older blacks are less likely to be admitted
      into the hospital, compared to their white counterparts (OR 0.68, 95%CI 0.52
      0.89). Elderly persons who perceive their health status as being fair or poor are
      three times as likely to be hospitalized than those who perceived their health
      status as excellent (OR 2.99, 95%CI 2.15-4.15). Those with impairment in
      activities of daily living are twice as likely to be confined to the hospital
      than those without impairment (OR 1.78, 95%CI 1.64-1.96). Elderly persons living
      with nonrelatives are three times as likely to be admitted for short hospital
      stays than those living with spouses (OR 2.90, 95%CI 1.44-5.82). Future
      identification of predictors of hospital admissions in the elderly may help
      characterize those at risk and perhaps allow for focused and timely intervention.

PMID- 14717473
TI  - Birthweight, rapid growth, cancer, and longevity: a review.
AB  - The fetal growth restriction hypothesis states that retarded growth in utero
      promotes health problems later in life. While most of the studies on intrauterine
      growth retardation (as measured by birthweight) confirm this hypothesis, many
      researchers have found flaws in these studies. In addition, many studies have
      found either no correlation or a positive relation between birthweight (BW) and
      adult blood pressure or mortality. Furthermore, high BW leads to greater adult
      obesity and chronic disease, and increasing macrosomia in newborns raises the
      risk for birth-related problems. Increased cancer risk is also tied to higher BW,
      and catch-up or accelerated growth generally has negative health effects. Adult
      height has been found to correlate with greater BW and birthlength (BL), and
      several studies have found an inverse relation between height and longevity.
      Paradoxical findings, such as lower BW and low levels of cardiovascular disease
      in the developing world, are presented. Within 25 years, genetic engineering will
      allow in utero alterations to the fetus, resulting in higher BW and taller
      adults. The authors suggest that increased BW leading to larger adult body size
      has dangerous implications in terms of human health and survival.

PMID- 14717474
TI  - Incidence of glove failure during orthopedic operations and the protective effect
      of double gloves.
AB  - OBJECTIVE: To determine the usefulness of double gloves in protecting against the
      exposure of surgical team members' hands to blood. METHODOLOGY: Five-hundred
      ninety-six gloves were studied during 71 orthopedic operations using the water
      loading test (filling a glove with water and occluding its cuff tightly to
      identify leaking points). RESULTS: In all, 73 glove perforations occurred, but
      only nine resulted in exposure to blood (blood touching the skin). The incidence
      of glove perforation was 12% (73/596), and overall exposure (blood touching the
      skin) per operation was 13% (9/71). The latter would have been 87% (62/71) but
      for the use of double gloves. Sixteen percent of the perforations in double
      gloves were in the inner gloves, while 84% were in the outer gloves. Exposure of
      surgeons was reduced from 54% to 10%, first assistants from 27% to 3%, and second
      assistants from 7% to 0 (p < 0.02, df = 2) by double-gloving. Significantly more
      perforations occurred during operations on bone, compared with soft tissue
      operations, p < 0.0001, RR = 4 (95% CL 1.87-8.55). The most common sites of glove
      perforation were the index finger (47%), thumb, and the palm region: 14% each.
      More glove perforations occurred in nondominant hands. CONCLUSION: Double-gloving
      offers additional protection to surgeons and assistants by preventing hand
      exposure to blood intraoperatively.

PMID- 14717475
TI  - Prevalence of bacterial pathogens in infected wounds in a tertiary hospital, 1995
      2001: any change in trend?
AB  - BACKGROUND: Wound care is a very important aspect of surgical care. Knowledge of
      the epidemiology of bacterial pathogens associated with infected wounds is
      critical in formulating policies on infection control. OBJECTIVE: To determine
      the prevalence of bacterial pathogens in wounds from various units of a Nigerian
      tertiary hospital orthopedics and traumatology department, as well as changes
      over time, if any, in the prevalence rates. METHODS: A retrospective study was
      conducted using laboratory records from 1995 to 2001. RESULTS: 670 bacterial
      isolates from 629 patients were studied. The most common isolates were
      Pseudomonas spp.-29.9%, and Staphylococcus aureus (S. aureus)--27.5%. Others were
      Klebsiella spp.-18.5%, Proteus spp.--15.1%, and Escherichia coli (E. coli)--7%.
      The least common were Streptococci--2%, and Enterococci--0.3%. Pseudomonas spp.
      accounted for 33% of isolates in the adult wards, while S. aureus was 21% and E.
      coli 8%. The pattem is similar in the pediatric ward (33.9%, 23.7%, and 8.5%,
      respectively) and Intensive Care Unit (ICU) (40%, 6.7%, and zero, respectively).
      S. aureus was the most common isolate from the orthopedic clinics (OPD) 40%, and
      the A&E (35%), followed by pseudomonas spp.-25.4% and 19%, respectively. The odds
      of a wound being infected with Gram-negative bacilli among inpatients compared
      with outpatients is 2.44 (95% CL = 1.72-3.47; P = 0.0000003) Between 1995 and
      2001, the prevalence of Gram-positive bacteria decreased, while that of Gram
      negative bacilli increased. The prevalence of Pseudomonas spp. and S. aureus also
      increased. CONCLUSION: Wounds from patients in the orthopedics and trauma
      services are more frequently infected with Gram-negative bacilli than by Gram
      positive bacteria. The prevalence of the former is higher in the ICU and least in
      the OPD. Pseudomonas spp. was the most common isolate. It was more common among
      inpatients, while S. aureus was more common among outpatients. The prevalence of
      Pseudomonas spp. in particular and Gram-negative bacilli in general is
      increasing.

PMID- 14717476
TI  - Familial clinodactyly of the fifth finger.
AB  - We describe a caucasian family of which whom five members in three generations
      had clinodactyly of the fifth fingers. This report confirms that clinodactyly of
      the fifth finger can be transmitted as an autosomal dominant trait.

PMID- 14717477
TI  - Noncompliance leading to drug accumulation resulting in phenytoin toxicity.
AB  - Phenytoin is effective in suppressing tonic-clonic and partial seizures, and is
      widely used for initial therapy, particularly in adults. Ninety percent of
      phenytoin is protein bound and entirely eliminated by hepatic metabolism. The
      major metabolite of phenytoin, 5-(p-hydroxyphenyl)-5phenylhy-dantoin (5HPPH) is
      excreted in the urine. Higher phenytoin levels for a given dose of phenytoin can
      be seen in alcohol intoxication, hepatic and renal failures, hypoalbuminemia,
      nephrotic syndrome, trauma, and AIDS. Noncompliance can lead to accumulation of
      the drug-causing toxicity. We present a patient with acute alcohol intoxication
      who developed phenytoin toxicity due to noncompliance with the drug.

PMID- 14717478
TI  - Multifocal papillary-cystic neoplasm of the pancreas.
AB  - This case report describes the second known instance of a multifocal capillary
      pancreatic neoplasm. Both cases occurred in young African American females. A
      less-than-total pancreatectomy was performed to maintain endocrine function.

PMID- 14717479
TI  - Advanced gastrointestinal stromal tumors successfully treated with imatinib
      mesylate: a report of two cases.
AB  - Activation of kit-receptor tyrosine kinase occurs in all cases of
      gastrointestinal stromal tumors, regardless of the mutation status of kit.
      Imatinib mesylate (STI 571,Gleevec) is a selective inhibitor of certain protein
      tyrosine kinases. It has been shown in preclinical models and clinical studies to
      have activity against such tumors. The aim of the present study was to report the
      efficacy of imatinib mesylate in the treatment of advanced gastrointestinal
      stromal tumors. Two adults with histologically confirmed, unresectable, and
      metastatic gastrointestinal stromal tumors that expressed CD117 (a marker of kit
      receptor tyrosine kinase) were identified at our institution during 2000-2002. As
      the diseases were advanced and not amenable to surgery, chemotherapy, or
      radiation therapy, imatinib mesylate was used, because this targeted inhibitor
      has been shown to be active against advanced gastrointestinal stromal tumors and
      has a mild toxicity profile. Imatinib mesylate induced a sustained response in
      both patients with advanced unresectable or metastatic gastrointestinal stromal
      tumors. Inhibition of the KIT signal-transduction pathway is a promising
      treatment for advanced gastrointestinal stromal tumors, which resist conventional
      chemotherapy.

PMID- 14717480
TI  - Emerging opportunistic fungal infections: where are we heading?
AB  - Medical mycology involves the study of pathogenic fungi and their identification
      in the laboratory. Mycology has developed into a field that demands the attention
      of all clinicians treating patients in hospitals. Interest in medical mycology
      has grown in recent years due to a dramatic rise in the rates of fungal
      infections. An overview of well-known medically significant opportunistic fungi,
      such as Candida, Cryptococcus, Aspergillus and Zygomycetes, as well as emerging
      fungal pathogens, are discussed. Antifungal failures in these individuals are
      high; consequently, mortality rates are also high, despite standard therapy with
      amphotericin-B, lipid-associated formulation of amphotericin-B and the azoles.
      This underscores the need for new approaches and therapies to improve outcomes in
      high-risk individuals.

PMID- 14717481
TI  - Nuremberg and Tuskegee: lessons for contemporary American medicine.
AB  - The activities of German doctors during the Nazi regime are well known and
      documented. They include efforts at eugenic sterilization and euthanasia,
      gruesome medical experimentation, and contributions to genocide. The German
      medical profession embraced the Nazi ideology of racial superiority. Nazi doctors
      enthusiastically perverted traditional medical mores of viewing each patient as a
      full individual towards a misguided sense of protecting the racial well-being of
      the nation from the perceived threat of certain groups of people. Similarly, some
      20th-century American physicians engaged in activities prompted by a misguided
      sense of patients' worth as individuals. This essay will examine the ethical
      problems of Nazi medicine and ethical missteps in the United States in the
      context of challenges for contemporary physicians, particularly the way in which
      we refer to our patients.

PMID- 14717482
TI  - Changing mindsets for changing times.

PMID- 14717483
TI  - Paclitaxel treatment article misleading.

PMID- 14717484
TI  - Stepwise surgical approach for in vivo expansion of epithelial stem cells to
      treating severe acute chemical burns with total limbal deficiency.
AB  - To describe the clinical outcome of a new surgical treatment for the acute stages
      of severe corneal burn injury and its complications, a prospective study of five
      acute corneal burn patients with severe limbal damage was performed. Amniotic
      membrane transplantation (AMT) and conjunctival limbal autograft (CLAU) was
      performed at the acute stage of corneal burn injury to reconstruct the damaged
      ocular surface (step I). Three to six months later, the opaque central part of
      the amniotic membrane containing in vivo grown corneal stem cells were removed
      and retransplanted to the defect created after the removal of pseudopterygium
      (step II). All injured eyes were successfully treated, but in one eye with marked
      stromal lysis, three-layered AMT and penetrating keratoplasty with
      retransplantation of in vivo grown corneal stem cells was performed. In the
      former cases, visual acuity was greatly improved more than three lines (ranging
      from 3 to 12 lines). In short, retransplantation of in vivo grown corneal stem
      cells after AMT and CLAU is a recommendable modality for restoring a stable
      corneal epithelium of a severely burned ocular surface in the acute stage and can
      be considered a preventative measure for avoiding late onset complications.

PMID- 14717485
TI  - Effects of viscoelastic material on the corneal endothelial cells in
      trabeculectomy with adjunctive mitomycin-C.
AB  - We evaluated the change of corneal endothelium after trabeculectomy with
      mitomycin-C soaking (0.2 mg/ml, 2.4 +/- 1.2 minutes) and the effect of
      viscoelastic material in reducing this change. In randomly selected cases, 0.05
      ml of sodium hyaluronate(Healon) was injected into anterior chamber (Healon
      group, n = 20), and same amount of balanced salt solution was injected in the
      other eyes (Control, n = 18) at the beginning of surgery. There were no
      differences in clinical variables and specular microscopy result between 2 groups
      before surgery. After surgery, the change of endothelial cells were significantly
      reduced in Healon group (cell density; -2.5 +/- 1.6%, variability of cell area;
      5.8 +/- 2.5%, and percentage of hexagonal cell; -2.2 +/- 0.7%) compared to
      control group (-7.7 +/- 6.0%, 8.9 +/- 4.4%, and -4.8 +/- 3.5% respectively, p <
      0.01). In trabeculectomy with mitomycin-C, the damage to the corneal endothelium
      was reduced significantly by injecting the viscoelastic material without
      significant complication.

PMID- 14717486
TI  - Relationship between topographic patterns and corneal astigmatism in Korean
      adults.
AB  - The anterior corneal surface is one of the most important elements determining
      the optical performance of the eye. Corneal topography provides quantitative data
      about the anterior corneal surface. We studied the corneal topography of 200
      normal corneas in 110 adult subjects. All of the eyes were examined using the
      Corneal Analysis System (EyeSys 2000, Houston, Texas). The topographic maps were
      grouped into the following patterns: round, oval, symmetric bow tie, asymmetric
      bow tie, and irregular. The symmetric and asymmetric bow tie patterns were the
      most common topographic pattern (33.0%, and 32.5%, respectively) in our study
      population, followed by oval (14.5%), irregular (12.5%), and round (7.5%)
      patterns. The mean corneal astigmatism calculated from videokeratographic data
      was 0.32 D for round, 0.63 D for oval, 1.16 D for symmetric bow tie, 1.21 D for
      asymmetric bow tie, and 0.43 D for irregular patterns. There were significant
      differences among the corneal astigmatic values in the topographic patterns (p <
      0.01, Gabriel post hoc test). The distributions of symmetric and asymmetric bow
      tie patterns were skewed toward greater amounts of corneal astigmatism. In
      conclusion, the results of this study demonstrate the relationship between
      topographic patterns and corneal astigmatism and should provide one possible
      normal standard for corneal topography in Korean adults.

PMID- 14717487
TI  - Nitric oxide mediates epinephrine-induced apoptotic cell death of trabecular
      meshwork cells in vitro.
AB  - To evaluate the effect of epinephrine on the cellular proliferation and
      production of nitric oxide (NO) in trabecular meshwork (TM) cells, cultured
      porcine TM cells were exposed to epinephrine at various concentrations, with and
      without its NO inhibitor, N(omega)-Nitro-L-arginine methyl ester (L-NAME). The
      proliferation of TM cells and the production of NO were quantified by rapid
      colorimetric assays. Acridine orange/Hoechest 33342 staining and flow cytometry
      were done to evaluate apoptosis. Epinephrine inhibited the proliferation of
      cultured TM cells and produced NO at significant levels in a dose-dependent
      manner. However, the antiproliferative effect of epinephrine was abolished by L
      NAME. Fluorescent microscopy and flow cytometric analysis revealed that
      epinephrine induced apoptotic cell death, which was suppressed by L-NAME. The
      current results suggest that the inhibitory effect of epinephrine on TM cell
      survival is associated with NO production. NO-mediated apoptosis may be involved
      in this epinephrine-induced antiproliferative effect on TM cells.

PMID- 14717488
TI  - A comparison of the clinical effect between e-PTFE membrane-tube implant and
      Ahmed glaucoma valve implant for the treatment of refractory glaucoma.
AB  - In order to compare the clinical efficacy of expanded polytetrafluoroethylene
      membrane-tube implant (MT implant) and Ahmed implant in the treatment of
      refractory glaucoma, the medical records of the patients who had been followed-up
      for more than 1 year after glaucoma implant surgery were reviewed
      retrospectively. Either MT or Ahmed implants were selected randomly and implanted
      by one surgeon in patients with refractory glaucoma. There was no significant
      difference in clinical variables such as age, intraocular pressure and ocular
      surgery history between the MT implant and Ahmed implant groups (n = 20 eyes of
      19 patients in each group) before surgery. The course of change in intraocular
      pressure and the number of anti-glaucoma medications were not significantly
      different between the 2 groups during the entire study period (p > 0.1). Kaplan
      Meier analysis for intraocular pressure control between 6 and 21 mmHg showed 90%
      and 95% at 6 months, and 85% and 85% at 12 months, in the MT and Ahmed groups,
      respectively (p = 0.982). A few self-limiting complications, all within the first
      month after surgery, were noted in each group. In this study, MT implant showed
      comparable results to Ahmed implant. MT implant may be useful as a good
      substitute for other currently used implants without any loss in efficacy or
      increase in risk, and with potential advantage coming from its soft consistency
      and small volume.

PMID- 14717489
TI  - Management of hypotony after trabeculectomy with mitomycin C.
AB  - The purpose of this study was to determine the incidence and risk factors of
      hypotony and the effectiveness of medical and surgical treatment. A total 117
      eyes of 103 patients that underwent trabeculectomy with mitimycin C (MMC) between
      1993 and 2000 were reviewed. Hypotony was treated with the following methods in a
      stepwise manner: medical treatment, intrableb autologous blood injection,
      additional sutures to the scleral flap, necrotic bleb excision and advancement of
      the forniceal conjunctival flap. Hypotony developed in 30 eyes (25.6%) of 26
      patients, among, which hypotonic maculopathy developed in 11 eyes (9.4%). The
      risk factors of hypotony were young age and primary open angle glaucoma. Because
      of no light sense, 6 of the 30 hypotonic eyes were not treated. Nineteen (79.2%)
      of the 24 treated hypotonic eyes were successfully managed. Five eyes, 3 with
      hypotony but maintaining visual acuity and 2 with follow-up loss, were not
      included in the success group. The mean intraocular pressure (IOP) before
      treatment, 2.5 +/- 1.2 mmHg, increased to 8.3 +/- 4.0 mmHg at 18.5 months follow
      up. The stepwise treatment seems to be a useful method to manage hypotony after
      trabeculectomy with MMC.

PMID- 14717490
TI  - Cataract surgery in patients with acute primary angle-closure glaucoma.
AB  - We investigated the results of cataract surgery in acute angle-closure glaucoma
      patients whose intraocular pressure (IOP) was not controlled with conventional
      treatment. We compared postoperative IOP and best corrected visual acuity (BCVA)
      with preoperative data in 10 eyes of 10 patients who had undergone cataract
      surgery for acute angle-closure glaucoma. Initial and preoperative mean IOP were
      50.0 +/- 6.4 mmHg and 34.9 +/- 9.3 mmHg, respectively. Mean follow-up was 6.3 +/-
      5.9 months. Postoperative mean IOP was 12.0 +/- 4.2 mmHg. All eyes were
      controlled at less than 21 mmHg and seven of them (70%) were controlled at less
      than 21 mmHg without medication. Postoperative BCVA was improved in 9 eyes. The
      complications were transient IOP elevation in 2 eyes and exudative membrane in 4.
      Cataract surgery may be effective to control IOP and improve visual acuity in
      patients with acute angle-closure glaucoma. However, follow up is necessary
      because of a high incidence of postoperative complications.

PMID- 14717491
TI  - Clinical results of a scleral fixation of the posterior chamber intraocular lens,
      through sclerotomies, 1 mm posterior to the limbus.
AB  - The aim of this study was to evaluate the clinical outcomes of scleral fixation
      of a posterior chamber intraocular lens and an anterior vitrectomy through
      sclerotomies, 1 mm posterior to the limbus. The study comprised of seven eyes
      that required a scleral fixation. Sclerotomies, 1 mm posterior to the limbus,
      were performed using a 20G sclerotome at the 2 and 8 o'clock positions. Group 1
      was defined as four eyes requiring scleral fixation of the secondary IOL
      (Intraocular lens), and group 2 as three eyes where dislocated IOLs were
      repositioned and fixed to the sclera via sclerotomy sites. In all the eyes, the
      knot of string (10-0 prolene, W1713, Ethicon, USA) was buried. Postoperatively,
      the visual acuity was greatly improved, by more than 4 lines in the Snellen
      visual acuity chart, with the exception of one case of macular degeneration. The
      scleral fixation of the IOL through sclerotomies, 1 mm posterior to the limbus,
      had advantages in that the scleral fixation of the IOL could be achieved through
      sclerotomy sites, and the anterior vitrectomy parallel to the iris plane.

PMID- 14717492
TI  - Comparison of venous filling times and SLO findings at each quadrant region in
      diabetic retinopathy.
AB  - Our purpose is to evaluate the correlation of retinal venous filling time (VFT),
      which reflects the peripheral retinal microcirculation in diabetic retinopathy,
      with fluorescein angiography (FAG) findings such as microaneurysm (MA), non
      perfusion area (NP), neovascularization (NV) and relative retinal venous diameter
      (RRVD), and further, to evaluate the correlation between arteriovenous passage
      time (AVPT) and these factors. Partial F-test (multiple regression analysis) was
      performed on patients (32 eyes of diabetic retinopathy) who underwent video FAG,
      using scanning laser ophthalmoscope. In the four quadrants, VFT was compared with
      each MA, NP, and NV at each vascular arch at a distance of one disc diameter
      distant from the optic disc. VFT was significantly correlated to RRVD, NP, and NV
      at each quadrant (r > 0.7). However, AVPT was not significantly correlated to any
      of the factors studied. Delayed VFT was associated with the hemodynamic change of
      the peripheral retinal microcirculation at each quadrant in diabetic retinopathy.
      VFT can be used as an index to indicate the peripheral microcirculation of the
      retina.

PMID- 14717493
TI  - Platelet activation in patients with diabetic retinopathy.
AB  - To clarify the diabetic complications mediated by increased platelet activity, we
      undertook a study of the mean platelet component (MPC), as determined by an
      automated hematologic analyzer (ADVIA 120, Bayer). Prothrombin time (PT),
      activated partial thromboplastin time (aPTT), and fibrinogen were also measured
      to investigate blood viscosity abnormalities. MPC was determined in 100 healthy
      controls and in 100 diabetic patients, the latter of which were subdivided into
      no diabetic retinopathy (DR) (n = 25), nonproliferative DR (n = 30), and
      proliferative DR (n = 45) groups. The mean MPC level was 26.9 g/dl in the control
      group and 22.5 g/dl in the diabetic patients (p < 0.05). PT and aPTT were similar
      for the diabetic patients and the controls; however, their corresponding
      fibrinogen levels were significantly different between the two groups(3.26 +/-
      1.14 g/L vs. 4.21 +/- 2.35 g/L, p < 0.05). Our results suggest that platelet
      hyperfunction in diabetic patients may be implicated in the pathogenesis of
      diabetic retinopathy.

PMID- 14717494
TI  - Indocyanine green angiography of retinal astrocytomas associated with tuberous
      sclerosis.
AB  - As small astrocytic hamartomas can sometimes be missed during routine
      ophthalmoscopy in patients with tuberous sclerosis, fluorescein and/-or
      indocyanine green angiography maybe more helpful in identifying such small
      astrocytomas. In fluorescein angiography, astrocytomas show gradually increasing
      hyperfluorescence due to the vascular permeability of astrocytomas. In
      indocyanine green angiography, astrocytomas appear hypocyanescent, most
      prominently during the late phases. We report the indocyanine green angiographic
      findings of retinal astrocytomas in a patient with tuberous sclerosis.

PMID- 14717495
TI  - A case of blowout fracture of the orbital wall with eyeball entrapped within the
      ethmoid sinus.
AB  - Blowout fractures, fractures of an orbital wall, are a common result of orbital
      injury. The author has experienced a case of a 66-year-old man who sustained a
      blowout fracture of the orbital wall with his intact eyeball entrapped within the
      ethmoid sinus. After undergoing a successful reduction surgery, the eyeball was
      repositioned to its original position, but the patient lost extraocular motility
      as well as vision. The final visual acuity was perception of light as a result of
      traumatic optic nerve injury and secondary retinal ischemia.

PMID- 14717499
TI  - Building strength through partnerships.

PMID- 14717500
TI  - Perilous journey: Canadian nursing research in 2009.

PMID- 14717501
TI  - What will change in nursing practice over the next five years?

PMID- 14717502
TI  - Nursing entrepreneurship: instilling business acumen into nursing healthcare
      leadership.

PMID- 14717503
TI  - Fitting in or standing out: what will change in nursing education over the next
      five years?

PMID- 14717504
TI  - The Health Council of Canada: a speculation on a constructive agenda.

PMID- 14717505
TI  - Developing guidelines for an interdisciplinary practice approach: administration
      of oral medications in a community mental health setting.
AB  - Mental health reform, health services restructuring and changes in mental health
      legislation have resulted in a shift from hospital-based to community-based
      treatment for individuals with serious and persistent mental illness. A system
      wide response to this trend has been the implementation of interdisciplinary
      Assertive Community Treatment (ACT) teams in the province of Ontario. The need
      for efficient, cLient-centred versus discipline-centred community care has
      prompted ACT teams to challenge traditional scopes of practice. This paper
      describes the Oral Medication Administration Guidelines Project as a mechanism
      for facilitating innovative team-based work design for oral medication
      administration in the community. The resulting provincewide guidelines can assist
      interdisciplinary ACT teams to design relevant training, improve work
      efficiencies and implement policies and procedures to manage client risk in
      relation to oral medication administration in the community.

PMID- 14717506
TI  - Helping ACT live up to its potential.

PMID- 14717507
TI  - Making the transition: staff nurse to front-line nurse leader.
AB  - This paper discusses the challenges that staff nurses face when moving into
      formal Leadership positions. Current transition strategies for nurses are
      presented, including a critical analysis of organizational and individual factors
      that enhance or impede the transition to front-line nurse leadership positions.
      Recommendations outline essential practices, resources available and support
      networks that enable a smooth transition into these positions. Reflections on the
      author's personal transition to a front-line nurse leadership position are
      included.

PMID- 14717508
TI  - Leadership success demands organizational investment.

PMID- 14717509
TI  - Honours education: releasing leadership potential.
AB  - There is debate within the nursing profession in regard to determining the best
      approach to Leadership development for the new millennium. Should nursing adopt
      career pathways Like other disciplines that enable individuals to develop
      leadership potential in a timely fashion? St. Francis Xavier University (StFXU),
      the number one ranked undergraduate school in the country (DeMont 2002), has
      established an innovative strategy that promotes Leadership development at the
      undergraduate level. It has launched a special stream of its BScN program that
      culminates in an honours degree. The program, the first of its type in Canada, is
      designed to produce nursing leaders and scholars who will possess the core
      competencies required for leadership in diverse environments. This paper
      discusses the role of honours education in nursing, describes the curriculum and
      related Learning activities in the StFXU honours program and explores the
      benefits and challenges that an honours program has to offer. The findings will
      benefit nurse leaders in educational and practice settings, professional
      organizations and policy arenas who are interested in influencing the development
      of leadership in nursing.

PMID- 14717510
TI  - Oral hygiene in the elderly: a quality improvement initiative.
AB  - This paper describes a unit-based quality improvement initiative to ameliorate
      mouth care of elderly residents in a long-term care facility. Using the Nursing
      Role Effectiveness Model developed by Irvine et at. (1998) as the organizing
      framework, this project highlights the importance of the nurse's role in quality
      improvement initiatives.

PMID- 14717511
TI  - Evaluation of a leadership development intervention.
AB  - Parallel to the shortage of clinical nurses is the diminishing pool of nurses who
      aspire to leadership roles in healthcare. The authors of this paper report on the
      evaluation of an intervention administered to a group of Canadian nurses designed
      to assist participants to value leadership and to develop knowledge, skills and
      attitudes required for effective leadership. A one-group pre-test, post-test
      quasi-experimental design guided the study. All participants received a five-day
      residential leadership development intervention. Participants acted as their own
      controls and were assessed, both immediately before intervention implementation
      and three months later, on the self- and observer-reported leadership practices
      as well as self-reported levels of burnout. Results indicated that a
      concentrated, residential leadership development intervention is effective in
      strengthening leadership behaviours performed by both already established and
      aspiring nurse leaders from the perspective of observers, but not from self
      reported assessments. No significant changes in self-reported burnout levels were
      found. It is possible to deliver leadership development interventions to both
      established and aspiring nurse leaders that result in fairly rapid improvements
      in observed leadership practices.

PMID- 14717512
TI  - Teaching evidence-based healthcare management: context and overview of the
      special issue.

PMID- 14717513
TI  - The impact of evidence on teaching healthcare management.
AB  - As healthcare management becomes more responsive to market demands, healthcare
      management education must prepare a more sophisticated and effective product. The
      author reviews the barriers to change in education and suggests that education
      will evolve to a new business model emphasizing "small bites" that are directly
      related to work needs and often learnable at the worksite, as well as integrative
      materialbest learned in a university environment. The ultimate model will have
      the following characteristics: 1. Managers' learning will be continuous, and will
      be recorded in individual certified "life transcripts" of mastery. 2. Learning
      will be performance driven, where performance is measured as contribution to the
      employer's goals and the patients' needs. 3. Learning will be flexible as to
      site, medium, and timing. 4. Managers' learning programs will emphasize recurring
      evaluation, celebration, and goal-setting.

PMID- 14717514
TI  - Evidence-based teaching: a course in health services management.
AB  - This article traces the development of a course in health services management
      over 40 years and presents the course within a context of teaching evidence-based
      management. One emphasis of the course is on teaching through storytelling-
      students developing learning capability to listen to what each stakeholder has to
      say, and then figuring what to do about it. Students share evidence from the
      professor's own work experience, the student's own work experience, peer-reviewed
      published articles, and case studies.

PMID- 14717515
TI  - Teaching future healthcare financial managers to use evidence.
AB  - There is a growing movement toward evidence-based management in healthcare. This
      movement extends to healthcare financial management. However, there are barriers
      to the use of evidence by healthcare financial managers. These barriers are
      largely the result of culture (management culture is substantially different from
      clinical culture) and education. If healthcare financial managers are to become
      better at generating and using evidence, educators must do a better job of
      preparing them to do so. If we provide more education regarding the goals of
      research and about the different types of research methods, then healthcare
      financial managers canbecome educated consumers of evidence. If we provide more
      examples of evidence that has been generated by research in our classes, and if
      we give the students experience in gathering evidence, we have a chance of
      increasing the use of evidence-based management in healthcare.

PMID- 14717516
TI  - Refocusing future faculty on evidence-based health services management research.

PMID- 14717517
TI  - Development of current faculty in evidence-based healthcare management research
      and teaching.

PMID- 14717518
TI  - Use of evidence in implementing competency-based healthcare management teaching.
AB  - Current efforts to develop a coherent list of health management competency
      domains supported by a set of sub-competencies and mapped to behavioral abilities
      are laudable. If we wanted to be evidence-based in our implementation of
      competency-based teaching in our educational programs, however, then as a minimum
      we must demonstrate the empirical association between individual's competency
      attainment and subsequent job performance and other desired outcomes. Assuming
      the association is positive and significant, we then need to demonstrate the
      association between the educational programming and individuals' competency
      attainment, in order to identify the approach to educational programming that
      best develops competencies. Inherent in conducting this research is articulating
      credible measures of complex and multifaceted concepts: educational programming,
      competency attainment, and job performance. Nevertheless, more rigorous evidence
      regarding the links between our educational approaches, our graduates'
      competencies, and their subsequent job performance would benefit us and move us
      closer to having evidence guide our educational system in health management.

PMID- 14717519
TI  - Teaching evidence-based management: where do we go from here?
AB  - Recently we talked with executive directors of healthcare organizations about the
      sources of information they use when conducting research. The responses were very
      similar. They preferred "googling," reading trusted trade journals, and reading
      more generic business literature such as Harvard Business Review. When asked if
      they ever read and used healthcare management research, they said the articles
      were often inaccessible. First, as CEOs faced with the responsibility for their
      organization's performance, they want to know whether there is anything in the
      research that will help them run their organizations better. Unfortunately, as
      observed by Gary Mecklenburg in this issue, the focus in healthcare research is
      too frequently on research implications, not on what a CEO wants and needs to
      know. As a result, the research is not always relevant. Further, by the time the
      research is conducted and published (it is not infrequent for more than a year to
      elapse from submission to actual publication in a journal, and by then the data
      may be two or more years old), executives have moved on to other decisions. As
      one of the CEOs observed, there is a gap between what she needs to know and what
      the health management literature has to say. Second, managers have limited time,
      and information needs to be succinct and to the point if it is to be useful.
      Research articles are very time consuming to read, and as the CEOs commented,
      time is a precious resource. Research articles frequently devote considerable
      space to conceptual development and methods, and even when managerial
      implications are addressed, managers

PMID- 14717520
TI  - Evidence-based management at Henry Ford Health System: an interview with Nancy M.
      Schllichting. Interview by Anthony R. Kovner.

PMID- 14717521
TI  - Splenunculus masquerading as colonic malignancy.
AB  - A 60-year-old woman presented with a hard lump of 5 x 3 cm in the left
      hypochondrium of 4 months duration. Clinical evaluation and investigations
      pointed towards a probably malignant colonic growth near the splenic flexure. She
      underwent an exploratory laparotomy with resection of the lump with the
      associated colon. Histopathology proved it to be a splenunculus. The rarity of
      such a case is highlighted and the diagnostic challenge it poses is discussed.

PMID- 14717522
TI  - Acute portal vein thrombosis secondary to donor/recipient portal vein diameter
      mismatch after orthotopic liver transplantation: a case report.
AB  - The incidence of portal vein thrombosis in end-stage liver disease is estimated
      as varying between 5% and 21%, whereas in candidates undergoing liver
      transplantation, this is 3-13%. Portal vein thrombosis occurring after liver
      transplantation can be managed surgically by thrombectomy, retransplantation,
      splenorenal shunt, or Wall-stent placement, or nonsurgically by angioplasty,
      local high-dose infusion of thrombolytic agents, combination of portal
      thrombolysis, or embolization of a pre-existing spontaneous splenorenal shunt. We
      report a case of portal vein thrombosis after liver transplantation diagnosed on
      postoperative day 1 in a 57-year-old patient who received a liver from an 8-year
      old donor. The patient was successfully treated surgically with portal vein
      thrombectomy and systemic anticoagulation. Portal vein thrombosis, in this case,
      was considered to be secondary to size discrepancy between the donor and the
      recipient portal veins. Routine use of daily Doppler ultrasound was the key
      factor in early diagnosis.

PMID- 14717523
TI  - Cardiac and pericardial fistulae associated with esophageal or gastric neoplasms:
      a literature review.
AB  - Pericardial and cardiac fistulae secondary to esophageal or gastric tumors are
      considered exceptional. They have never been the object of a literature review.
      We reviewed the medical literature between 1881 and 2001, searching for all
      published cases of pericardial or cardiac fistulae developed from esophageal and
      gastric tumors or favored by the applied therapy to these tumors. The cases of
      metastasization, tumor spread, and neoplasic pericardial effusion without fistula
      were excluded. Fifty patients were identified, with one original case. More than
      half the cases (56%) occurred in the last 25 years. Substernal pain is the main
      symptom. The majority of patients present at least one condition favoring fistula
      formation. The auscultation of a water-wheel murmur may suggest a
      pneumopericardium and therefore a pericardial fistula, as does a purulent
      pericarditis. Arrhythmias, signs of ischemia, and hematemesis point toward a
      ventricular fistula. Neurological and hemostasis disorders may be suspect of an
      atrial lesion. Diagnosis should be made by the association of a scanner and a
      transit. Prognosis is bad: 76% of the patients die in the first month.
      Pericardial or cardiac fistulae are part of the differential diagnosis of
      thoracic pain in patients with esophageal or gastric tumors and in patients who
      were treated for these pathologies. The diagnosis must be as quick as possible.
      An operation (patients with a good prognosis) or the placement of a stent
      (patients with a bad prognosis) is the only chance of survival.

PMID- 14717524
TI  - Five years experience in surgical treatment of liver hydatidosis.
AB  - Liver hydatidosis is frequent in Santiago Del Estero. Different therapeutic
      procedures have been proposed, but surgery is still the best option. This
      observational retrospective analysis presents the authors' experience and
      results, with the goal of selecting the best surgical procedures. A total of 66
      patients with 89 cysts were evaluated between December 1997 and 2002. Sex, age,
      cyst localization, complication of cysts, surgical procedure, associated
      procedures, morbidity and mortality, and hospital stay were evaluated. Of 89
      cysts, 10 were complicated; of 66 patients, 59 had solitary cysts.
      Pericystectomy, Mabit procedure, liver resection, bipolar or tripolar drainage,
      and marsupialization were used. Morbidity was 22.72%, and mortality was 1.51%.
      The average hospital stay was 7.03 days. In the follow-up, 33 patients were
      evaluated, with only 1 recurrence. The results are similar to other published
      series. Complicated cysts have a more complex solution and evolution.
      Pericystectomy, Mabit procedure, and liver resections are the chosen surgical
      procedures in uncomplicated cysts. Laparoscopic surgery undoubtedly has a place
      in the treatment of liver hydatidosis.

PMID- 14717525
TI  - Efficacy of ultrasonic tissue dissector and tissue glue for laparoscopic partial
      nephrectomy in a porcine model.
AB  - The purpose of this study was to evaluate the efficacy and long-term tissue
      effects of ultrasonic dissector and cyanoacrylate glue during laparoscopic
      partial nephrectomy in a porcine model. Nine domestic pigs underwent laparoscopic
      left lower pole partial nephrectomy without vascular control. An ultrasonic
      tissue dissector was used to assist in the parenchymal incision, and the raw
      surfaces of the kidneys, including the exposed urinary system, were sealed with
      cyanoacrylate glue. No internal stents or additional sutures were placed.
      Intraoperative hemorrhages and urinary extravasation were recorded. The animals
      were humanely killed 28 days after undergoing the operations. The long-term
      effects of ultrasonic dissector and cyanoacrylate glue on the healing process of
      urothelium and renal parenchyma were determined histologically. All pigs survived
      the laparoscopic partial nephrectomy, and the blood loss ranged from 0 to 120 ml
      (mean, 60 ml). The average operative time was 89 +/- 10 min. The severity of the
      bleeding was minimal in six animals and moderate in three animals. No urinary
      extravasation was found using intravenous urography at the 28th postoperative
      day. No urinary fistula or renal abscess formation was found histologically.
      Cyanoacrylate glue infiltrated into the tissue defects and did not dissolve. The
      glue was encased by fibrotic tissue with minimal foreign body inflammatory
      reaction. Ultrasonic dissector was effective in achieving hemostasis during
      laparoscopic partial nephrectomy without the need of vascular control in pigs.
      Cyanoacrylate glue achieved good long-term adhesive power. The sealing effects
      provided by cyanoacrylate glue were adequate to prevent urinary extravasation
      from urothelial defects at least for 1 month.

PMID- 14717526
TI  - Retrosternal goiters: safety of surgical treatment.
AB  - Retrosternal goiters still pose a problem to expert endocrine surgeons. Whether
      surgery should be the treatment of choice or not remains controversial because of
      hypothetical increased morbidity rates associated with the surgical approach.
      Eighty-three patients were retrospectively reviewed for anesthetic risk,
      fibrobronchoscopic guidance for intubation, surgical technique, mortality and
      morbidity rates, and pathological findings. We found 6.09% of American Society of
      Anesthesiologists (ASA) I, 41.46% of ASA II, 40.24% of ASA III, and 12.19% of ASA
      IV risk. Twelve patients (14.45%) required fibrobronchoscopic guidance for
      intubation. Only one patient required a sternotomy. No mortality occurred. Seven
      patients (8.43%) had major complications, but there were no instances of
      permanent recurrent laryngeal palsy or hypocalcemia. Pathological examination
      revealed 9.63% incidence of malignancy. Surgery should be the treatment of choice
      for retrosternal goiters because there is a significant incidence of malignancy
      and an acceptable morbidity rate.

PMID- 14717527
TI  - Surgical management of chronic pancreatitis: current concepts and future
      perspectives.
AB  - Initial management of chronic pancreatitis is always conservative. All forms of
      nonsurgical intervention should be exhausted before surgery. Main indications for
      surgery in chronic pancreatitis are intractable pain, suspicion of malignancy,
      and complications from adjacent organs. Preoperative evaluation should include an
      evaluation of the severity of pain, interference of quality of life, and presence
      of chemical dependency and imaging examinations to determine the primary site of
      disease, presence of pancreatic ductal dilatation, and associated peripancreatic
      complications. The surgical treatment approach involves proximal or distal
      resection (depending on the main location of the disease) for small-duct disease
      and lateral pancreaticojejunal drainage for large-duct disease. The newer
      duodenum-preserving head resections of Beger and Frey and thoracoscopic
      transthoracic splanchnicectomy await good confirmatory, independent trials to
      confirm their efficiency in the surgical management of chronic pancreatitis. The
      V-shaped excision of ventral pancreas in association with a lateral
      pancreatojejunostomy is also an interesting alternative in the management of
      small-duct disease that is also under investigation. In recent years, a clear
      trend in favor of resectional procedures (including the newer nonanatomic
      pancreatic resections) has been observed.

PMID- 14717528
TI  - Laparoscopic Toupet versus Nissen fundoplication for the treatment of
      gastroesophageal reflux disease.
AB  - The Nissen fundoplication is the most popular laparoscopic operation performed
      for the surgical treatment of gastroesophageal reflux disease (GERD). However,
      for patients in whom esophageal peristalsis is documented to be weak
      preoperatively, use of a partial wrap, or Toupet procedure, has often been used
      as an alternative to lessen the potential for postoperative dysphagia. Recent
      reports have criticized the Toupet procedure as having a higher long-term failure
      rate than the Nissen approach, especially for patients with severe forms of GERD.
      We reviewed our experience performing laparoscopic antireflux surgery over a 7
      year period and compared the results of patients undergoing laparoscopic Nissen
      versus Toupet procedures. All procedures were performed at our institution by a
      single surgeon. Data recorded included preoperative demographic data,
      preoperative disease parameters, perioperative data, postoperative course, and
      symptom scores. Follow-up was based on a combination of medical records and phone
      interviews. There were 142 patients with complete records allowing review for
      this study. Of these, 118 underwent 122 Nissen fundoplications and 26 underwent
      27 Toupet fundoplications. Selection of the procedure was based on preoperative
      manometric studies. There were seven reoperations. Seven of the patients (28%)
      who underwent Toupet procedures had severe GERD, a percentage comparable to the
      Nissen group (31.6%). Preoperative parameters were comparable for both groups,
      although the Toupet patients had lower average preoperative LES pressures (9.79
      mmHg) than did the Nissen patients (16.1 mmHg, P < 0.05). The operative duration,
      operative blood loss, morbidity, length of hospitalization, need for reoperation,
      and efficacy in terms of relieving symptoms (average follow-up = 27.5 months)
      were comparable for both groups. Based on this experience, the Toupet procedure
      seems safe and effective in treating the symptoms of GERD, including patients
      with severe forms of the disease. We recommend its selective use in patients with
      preoperative esophageal hypomotility who are undergoing laparoscopic antireflux
      surgery.

PMID- 14717529
TI  - Carotid body tumors.
AB  - We present our approach to the management of patients with carotid body tumors,
      emphasizing the role of magnetic resonance angiography for the identification of
      these tumors. Medical records of all patients with carotid body tumors who were
      managed between 1991 and 2001 were retrospectively reviewed. Nine patients with
      carotid body tumors were identified. There were four males and five females,
      ranging in age from 28 to 74 years. Duplux scanning, computed tomography (CT)
      scanning, and angiography were performed for seven patients, whereas Duplux and
      magnetic resonance angiography were performed for the remaining two patients.
      Eight patients underwent successful excision of the tumor. Neither postoperative
      deaths nor strokes occurred. Temporary cranial nerve injury occurred in two
      patients. One patient developed local recurrence 5 years later. Early diagnosis
      of carotid body tumors with Duplex and magnetic resonance angiography is
      possible. Early surgery for carotid body tumors minimizes the risk of
      complications associated with large tumors.

PMID- 14717530
TI  - Emergency hernia repairs in elderly patients.
AB  - The aim of this study was to determine the clinical presentation, morbidity, and
      mortality and to identify the factors that might affect the outcome of emergency
      repair in elderly patients. A study of 143 patients (> 65 years old) who
      underwent emergency surgical repair for incarcerated external hernias during the
      period 1992-2001 was done. Fifty patients (35%) presented after 48 hours of
      symptoms onset. Coexisting diseases were found in 104 cases (77.7%). Bowel
      resection was required in 25 patients (17.5%). Overall morbidity was 46.2%, and
      major complications were seen in 17 cases (11.9%). Mortality was observed in
      seven patients (4.9%). Longer duration of symptoms, delayed hospitalization,
      concomitant illness, and high American Society of Anesthesiologists scores were
      significant factors linked with unfavorable outcome. To avoid the increased risks
      of emergency hernia repairs in the elderly, priority admission and early elective
      surgery should be used.

PMID- 14717531
TI  - [Rugen (Germany): hemogenetic study of an island population].
AB  - 24 haemogenetic markers (5 erythrocyte antigens, 7 polymorphisms of serum
      proteins. 12 polymorphisms of red cell enzymes) had been studied in up to 171
      individuals from the island of Rugen (Germany, Baltic Sea). The cluster analysis
      separates clearly the ugen sample just as the islands of Hiddensee and Ummanz
      from the neighbouring populations. The comparison of the data with neighboured
      larger populations as for instance Denmark, Hamburg or Sweden clearly results in
      an exceptional position of the island of Rugen. The possible reasons are
      discussed.

PMID- 14717532
TI  - Blood group frequencies in Romania: microregional and ethnic differences.
AB  - This study is based on the results of the blood group typing (AB0, MN, RH: D/d)
      of two samples from Romania and on literature data. The 40 population samples
      used are scattered on the today's territory of Romania. Some data refer to more
      or less endogamous villages or groups of villages which belong to the same
      marriage area, some data refer to towns with admixed populations. Samples of nine
      ethnic minorities have been included in the study. The results have been
      discussed on the basis of the historical and geographical background.

PMID- 14717533
TI  - Serological researches in the south of Moldavia in connection with the problem of
      the ethnogeny of the Gagauzes, the Moldavians and the Bulgarians.
AB  - With the aid of data of frequencies of genetically determined blood group
      systems, the authors have tried to show the basic ethno-genetic directional
      patterns in Southern Moldavia and in the Dniester-Carpathian-Danubian region in
      its entirety. Blood Groups A1A27B0, RHESUS, MN, and KELL have been determined in
      six random samples from four Gagauz villages (n = 330), one Moldavian village (n
      = 101) and one Bulgarian village (n = 96). The analysis of gene frequencies
      demonstrates genetic homogeneity of the total Gagauz population. Statistically
      reliable differentiation is observed only for the RHESUS system. It is possible
      now to suppose that the haemotological types of modern Gagauz and Bulgarian
      populations have been developed on the basis of the Balcanic serogenetic types,
      partially transformed under influence of gene flow from probably Central Asian or
      other eastern centers. The position of the Moldavians on the serogenetic map of
      Europe is less certain, due to a considerable ambiguity in the allele frequencies
      of the various blood group systems. Founder effects may account for these
      observations. However, the genetic distance and cluster analyses carried out on
      the frequencies of the surveyed blood group systems have shown the affinity of
      Moldavians with the Romanians and Eastern European populations.

PMID- 14717534
TI  - Genetical and epidemiological studies of polydactyly in Hungary.
AB  - Polydactyly is one of the most frequently observed human congenital limb
      malformations. Sporadic cases of polydactyly have been described, but most show
      an autosomal dominant pattern of inheritance. The purpose of this study was to
      investigate the frequency of polydactyly among children born between 1980 and
      1997 in Hungary. The predominance of the postaxial type over the preaxial one was
      less than expected. These malformations affected significantly more boys than
      girls. The proportion of children with low birth weight affected by polydactyly
      was higher than expected. Among mothers giving life to offspring with
      polydactyly, the prevalence was high in the older age group. We analysed the
      regional distribution in Hungary and the twin frequency in connection with
      polydactyly. From our results comparing it to the current literature data we made
      conclusions about the possible causes of the development of polydactyly.

PMID- 14717535
TI  - Size and shape modifications in Sardinian adolescent girls.
AB  - In females, menarche is the defining moment of puberty, the period of life when
      the greatest body changes occur. In the present study, the metric and
      morphological variations associated with sexual maturation are defined in 155
      Sardinian girls (10-17 years) and the role of some potentially influential
      variables is discussed: age, age at menarche and time since menarche. We studied
      thirty-eight anthropometric variables, the fat-free mass and the fat mass
      estimated by Bioelectrical Impedance Analysis. Statistical analyses were
      performed to evaluate the difference between pre- and post-menarcheal girls of
      the same age (Student's t-test) and to evaluate the different role played by the
      variables (principal components analysis, cluster analysis, multiple regression).
      The results demonstrate that the body dimensions of the adolescent girls mainly
      increase in concomitance with sexual maturation. The age at menarche influences
      the fat mass but not the distribution of visceral and subcutaneous fat. The time
      since menarche has also no effect on the distribution of subcutaneous fat.

PMID- 14717536
TI  - Five-class height-weight model for systematization of seventeen-year-old
      recruits' anthropometric data.
AB  - An anthropometric study of 552 Tartu city and Tartu county recruits aged 17 years
      was carried out. Height and weight, 33 anthropometric measurements and 12
      skinfolds were measured. Body fat percentage was assessed by Omron BF 300 hand
      held segmental body fat analyzer. From anthropometric measurements bone mass was
      derived by the Drink-water et al. (1986) equation, and total skeletal muscle mass
      by the Lee et al. (2000) equation. The data were systematized into five height
      weight SD-classes. There were 3 classes with harmony between height and weight
      class: 1--small (small height and small weight), 2--medium (medium height and
      medium weight), 3--large (large height and large weight), 4--weight class
      dominating (pyknomorphic) and 5--height class dominating (leptomorphic). It was
      revealed that in classes 1, 2 and 3 the height and weight increase corresponded
      to the increase in all heights, breadths and depths, circumferences, skinfolds,
      body fat, muscle and bone mass. In class 4 circumferences, skinfolds, body fat
      and muscle mass were bigger. In class 5 all heights and the relative bone mass
      were bigger. The present investigation confirms the hypothesis that the five
      height-weight class system is applicable to seventeen-year-old recruits.

PMID- 14717537
TI  - Anthropometric and physiological traits: age changes among the Oraon agricultural
      labourers of the Jalpaiguri District, northern West Bengal, India.
AB  - Data on anthropometric and physiological parameters were collected as a part of
      an ongoing biomedical research project on 197 adult Oraon agricultural labourers
      of the Jalpaiguri District, West Bengal, India. The analysis of the present data
      focuses attention towards the nature and extent of changes in adulthood in
      respect of anthropometric and physiological traits. The results reveal that the
      height increases up to 35 years of age, then declines, weight decreases after 40
      years of age, although males and females do not show similar results.
      Physiological parameters on the other hand reveal that the blood pressure
      increases with age and strength parameters i.e. grip strength and back strength
      declines after the age of 25 years or so. However, no generalization can be made
      out of this, because of the cross-sectional nature of the present study.

PMID- 14717538
TI  - [Sports anthropology investigation on female participants of the German Sports
      Aerobic-Masters compared to non-sports participating young females].
AB  - This investigation is based on the sports anthropology of 50 female participants
      of the German championships of Sport Aerobics (age range 16-35 years), whose
      constitutional body build parameters were compared to 50 female physical
      education students (age range 18-30 years) and 40 women (age range 18-35), who
      did not engage in sportive activities at all. Somatotyping and other sports
      anthropological techniques were performed according to Parnell (1958). Heath &
      Carter (1967), Conrad (1963) and Knussmann (1961a, 1961b) as well as proportion
      figures and phantom stratagem. In the North-American somatocharts the aerobic
      athletes were classified as ectomesomorph, whereas the physical education female
      students were found in the ectoendomorph area according to Parnell and the non
      sportive subjects remained on the mesoendomorph part. In the Heath-Carter
      somatochart, the physical education students and the non-sportive women were
      registered in the mesoendomorph and ectoendomorph areas. In the German systems
      the young women were placed in the leptomorph direction and mesoplastic in the
      Conrad typology. According to Knussmann, all the investigated groups were
      classified as ultramacrosom and superleptomorph. Some morphological differences
      can be detected by means of proportion figures and phantom stratagem. The aerobic
      athletes display a more athletic somatotype with an accentuated radio-ulnar
      breath. The aerobic group is also characterised by the smallest body fat
      percentage, whereas the non-exercising group shows the opposite. This is also
      proven by the body mass index.

PMID- 14717539
TI  - Variation of chicken technological meat quality in relation to genotype and
      preslaughter stress conditions.
AB  - The present study was aimed at estimating the genetic variability between lines
      of breast and thigh meat quality (pH decline, color, drip loss, and curing
      cooking yield) by comparing a slow-growing French label-type line (SGL) and a
      fast-growing standard line (FGL) of chickens exposed to different preslaughter
      stress conditions. The birds were slaughtered under optimal conditions or after
      exposure to 2 h of transport or acute-heat stress (2 h at 35 degrees C).
      Relationships between meat quality and stress sensitivity were investigated by
      measuring struggle during shackling and tonic immobility (TI) duration, 1 wk
      before slaughter, as an indicator of the basal level of fear of the birds.
      Although most of the meat quality indicators varied between the 2 lines,
      differences were muscle dependent. In concordance with a lower ultimate pH,
      curing-cooking yield of thigh meat was decreased for the FGL birds. In contrast,
      these birds had a higher curing-cooking yield and a lower drip loss of breast
      meat resulting from a less rapid pH decline in this muscle compared with SGL
      birds. Thigh meat characteristics were influenced by both preslaughter stresses,
      but no significant effects were detected for breast meat. The main effect of heat
      stress in thigh meat was a decrease of the ultimate pH and led to paler color and
      lower curing-cooking yield; opposite effects were obtained for transport. Breast
      meat was much more sensitive to physical activity of birds on the shackle line.
      Longer durations of wing flapping on the shackle line gave more rapid initial pH
      decline. Whatever the line, no relationship between TI duration and meat quality
      characteristics or activity was observed. The present study suggested that SGL
      birds could be at disadvantage due to more struggle during shackling and
      accelerated postmortem glycolysis, which is detrimental to the quality of breast
      meat.

PMID- 14717540
TI  - Relation between tonic immobility and production estimated by factorial
      correspondence analysis in Japanese quail.
AB  - Duration of tonic immobility (TI) is a well-established criterion of fearfulness
      in birds, but its relation to production traits has been little studied. TI and
      27 variables related to egg production and quality, feed consumption, and body
      condition were collected for 355 female Japanese quail. Experimental birds were
      the F2 generation from a reciprocal cross between a line selected for long TI and
      a line from a different origin and selected for early egg production. TI and
      several other variables had very asymetrical distributions so all variables were
      categorized, and the association between traits was studied by factorial
      correspondence analysis (FCA). Attributes of good versus poor layers were well
      separated by the FCA, but no association was obtained between TI and other traits
      on the primary axes of the FCA. Fearfulness, as measured by TI, was not related
      to levels of performance of egg laying quail. Secondary negative associations
      between TI and body temperature and between TI and residual feed consumption were
      obtained; however, they were marginal and need to be confirmed.

PMID- 14717541
TI  - Detection of different quantitative trait loci for antibody responses to keyhole
      lympet hemocyanin and Mycobacterium butyricum in two unrelated populations of
      laying hens.
AB  - Quantitative trait loci involved in the primary antibody response to keyhole
      lympet hemocyanin (KLH) and Mycobacterium butyricum were detected in two
      independent populations of laying hens. The first population was an F2 cross
      (H/L) of lines divergently selected for either high or low primary antibody
      responses to SRBC, and the second population was an F2 cross between 2 commercial
      layer lines displaying differences in feather pecking behavior (FP). Both
      populations were typed with microsatellite markers widely distributed over the
      genome with similar intervals between markers. Titers of antibodies binding KLH
      and M. butyricum were measured for all individuals by ELISA. Two genetic models
      were applied to detect QTL involved in the humoral immune response: a half-sib
      model and a line-cross model, both using the regression interval method. In the
      half-sib analysis, 2 QTL (on GGA14 and GGA27) were detected for the antibody
      response to KLH for the H/L population, and 2 QTL (on GGA14 and GGA18) were
      detected for the FP population. Only 1 QTL was detected for M. butyricum on GGA14
      in the FP population using the half-sib analysis model. Two QTL were detected for
      the FP population on GGA2 and GGA3 using the line-cross analysis model. A QTL for
      the primary antibody response to KLH detected on GGA14 was validated in both
      populations under the half-sib analysis model. The present data suggest
      differences in the genetic regulation of antibody responses to two different T
      cell dependent antigens.

PMID- 14717542
TI  - Active control of the growth trajectory of broiler chickens based on online
      animal responses.
AB  - The objective of the research reported here was to control the growth trajectory
      of broiler chickens during the production process based on an adaptive compact
      dynamic process model. More specifically, the daily feed supply was calculated,
      based on a model-based control algorithm, with the aim of following a previously
      defined target growth trajectory as close as possible. For the modeling of the
      dynamic growth response of broiler chickens to the control input, feed supply, an
      online parameter estimation was used. The developed control algorithm was able to
      grow the birds according to different target trajectories ranging from restricted
      (final BW of 1,800 g and 1,945 g in experiments 1 and 3, respectively) to
      compensatory growth trajectories (final BW of 2,400 g and 2,100 g in experiments
      2 and 4, respectively). The mean relative error (MRE) between the different
      predefined target growth trajectories and the realized growth trajectories ranged
      from 3.7% to 6.0%. With a few exceptions, the numerical values of feed conversion
      ratio and mortality after wk 1 were lower and the values of uniformity index were
      higher in the controlled groups compared with animals fed ad libitum. As a
      conclusion, it can be stated that integration of dynamic data-based modeling
      approaches with new hardware and sensing techniques to measure information from
      the animals should make it possible to control broiler growth trajectories.

PMID- 14717543
TI  - Accelerating embryonic growth during incubation following prolonged egg storage.
      1. Embryonic livability.
AB  - The hypothesis was proposed that shorter incubation periods and faster growth
      rates for long-stored eggs would improve embryonic survival and poult hatchling
      quality. Increased incubation temperatures were tested for their efficacy in
      improving embryonic livability in fertilized eggs stored for 15 d prior to
      setting in the incubator compared to controls stored for only 3 d. Two
      temperature treatments were applied. In experiment 1, a 37.8 degrees C set point
      for dry bulb temperature was used to accelerate development for the initial 2 wk
      compared to the controls at 37.5 degrees C. Following treatment, the accelerated
      embryos were returned to the same machine as the controls. In experiment 2,
      higher temperature exposure was only for the initial week of incubation. The
      temperature and storage treatments were in a completely random 2 x 2 factorial
      arrangement of treatments. At the completion of 28 d of incubation, survival
      rates of all treatments were determined by opening all nonhatching eggs to
      differentiate truly fertilized eggs from unfertilized. Hatchability was
      determined by dividing the total number of poults on a hatching tray by the
      number of fertilized eggs on a tray. Incubator trays were the experimental unit.
      Tissues were sampled in both experiments to verify treatment effects on growth
      and metabolism. Hatching times were observed at 4-h intervals during the actual
      hatching process beginning at 25 d of incubation. It was concluded that delayed
      growth and depressed metabolism of fertilized turkey eggs stored for 15 d can be
      compensated for by exposure to higher incubation temperatures for the initial 1
      or 2 wk of incubation.

PMID- 14717544
TI  - Accelerating embryonic growth during incubation following prolonged egg storage.
      2. Embryonic growth and metabolism.
AB  - The hypothesis was proposed that the improved embryonic livability observed when
      higher incubation temperatures were imposed on eggs stored for 15 d prior to
      setting might have basis in energy metabolism. To test the hypothesis, fertilized
      turkey eggs were incubated either for the first 2 wk of development (experiment
      1) or only the first week of development (experiment 2) at 37.8 degrees C
      compared with controls incubated at 37.5 degrees C. In both experiments, eggs
      were stored for either 15 or 3 d prior to setting. Viable embryos were selected
      randomly from each storage-by-incubation period treatment combination at 25 to 28
      d of incubation and were sampled for blood, heart, and skeletal muscle tissues.
      Tissues were weighed and assayed subsequently for glucose or glycogen content. In
      experiment 2, the randomly selected embryos from each treatment combination were
      sampled at 7, 14, 21, and 28 d of incubation. Embryos at 7 and 14 d were assayed
      on a whole body basis, whereas at 21 and 28 d the bodies were dissected, and
      heart, liver, and skeletal muscle tissues were weighed and assayed for glycogen
      and lactate. Blood samples were collected between 25 and 28 d of incubation as in
      experiment 1 and assayed for glucose, creatine kinase, lactate dehydrogenase, and
      thyroid hormone concentrations. In both experiments, accelerated development was
      noted due to higher temperature and enhanced embryonic carbohydrate metabolism,
      and elevated thyroid hormone concentrations were observed compared with controls.
      It was concluded that a possible mechanism for the improved livability of faster
      growing embryos observed after prolonged egg storage might be due to better
      utilization of carbohydrate.

PMID- 14717545
TI  - Effects of early age feed restriction and heat conditioning on heat shock protein
      70 expression, resistance to infectious bursal disease, and growth in male
      broiler chickens subjected to heat stress.
AB  - The effects of early age feed restriction and heat conditioning on heat shock
      protein (HSP) 70 expression, antibody production, resistance to infectious bursal
      disease (IBD), and growth of heat-stressed male broiler chickens were
      investigated. Chicks were divided into 4 groups: 60% feed restriction on d 4,5,
      and 6 (FR); exposure to 36 +/- 1 degrees C for 1 h from d 1 to 21 (HT);
      combination of FR and HT (FRHT); and control. From d 35 to 50, heat stress was
      induced by exposing birds to 38 +/- 1 degrees C and 80% RH for 2 h/d. On d 36,
      each bird was administered 10 times the normal dose of live IBD vaccine. After
      heat exposure, the FRHT birds had higher HSP 70 density (d 41) and weight gain
      (from d 35 to 49) and lower bursal histological score (BHS) (d 51) than their HT
      and control counterparts. The HSP 70 expression and BHS of FR birds were not
      significantly different from those of the other 3 groups during the heat exposure
      period. Heat shock protein 70 and BHS data were negatively correlated (r = -0.33,
      P = 0.0008). We concluded that FRHT could improve weight gain and resistance to
      IBD in male broiler chickens under heat stress conditions. The improved heat
      tolerance and disease resistance in FRHT birds could be attributed to better HSP
      70 response.

PMID- 14717546
TI  - Effect of intravenous endotoxin on blood cell profiles of broilers housed in
      cages and floor litter environments.
AB  - Commercial broilers are constantly exposed to airborne microorganisms and
      endotoxin (lipopolysaccharide, LPS). It has been shown that microbial
      contamination of the air was higher in broiler houses using floor litter than in
      broiler houses using netting-type floors. The current study evaluated the effect
      of housing conditions on blood leukocyte profiles and tested the hypothesis that,
      when compared to broilers reared in clean stainless steel cages (Cage group),
      broilers raised on floor litter (Floor group) should experience a higher
      environmental challenge and have a desensitized immune system that may exhibit
      better tolerance/resistance to subsequent intravenous LPS challenge.
      Hematological parameters were evaluated prior to and following i.v.
      administration of 1 mg/kg BW Salmonella typhimurium LPS (dissolved at 1 mg/0.25
      mL in PBS) or i.v. injection of 0.25 mL/kg BW PBS alone. The results showed that
      prior to LPS/PBS injection, broilers in the cage group had higher heterophil and
      monocyte concentrations, a higher B cell percentage within the lymphocyte
      population, and a higher heterophil to lymphocyte (H:L) ratio in the blood. The
      i.v. LPS injection resulted in 25% mortality in the cage group and 42% mortality
      in the floor group within 8 h post-injection. LPS reduced the concentrations of
      total white blood cells (WBC) and all differential WBC except eosinophils and
      increased thrombocyte concentrations within 1 h post-injection in both groups.
      All of these values returned to their respective pre-injection levels within 48 h
      post-injection in the surviving birds. The two groups exhibited similar overall
      hematological changes after LPS injection except that the cage group showed a
      higher H:L ratio at 8 h post-injection and a lower B-cell percentage within the
      lymphocyte population at 48 h post-injection when compared with the floor group.
      We concluded that the immune systems of broilers reared on floor litter were
      desensitized and exhibited less pronounced leukocyte responses to i.v. LPS when
      compared with those of broilers reared in clean stainless steel cages. However,
      such desensitization of the immune system did not help broilers survive
      subsequent i.v. LPS challenge.

PMID- 14717547
TI  - Comparison of sampling techniques for detection of Arcobacter butzleri from
      chickens.
AB  - Arcobacter butzleri is a causative agent of human enteritis that has been
      recently differentiated from the genus Campylobacter. Previous work suggests that
      its transmission to humans is likely through a foodborne route with a substantial
      tendency to be located on poultry carcasses. For reducing the incidence of this
      pathogen on commercial poultry, improved protocols are needed to sample and
      identify A. butzleri from infected birds prior to slaughter. The purpose of this
      study was to compare sampling methods for this emerging pathogen from chickens
      that were artificially inoculated per os with A. butzleri. We tested three
      sampling techniques commonly used to determine the microbiological quality of
      poultry: cloacal swabs, fecal samples, and environmental surface (drag) swabs
      collected when birds were 3, 5, or 7 wk old. These samples were cultured in
      Johnson-Murano enrichment broth and analyzed by PCR. Results indicate that
      environmental surface swabs yielded the highest recovery percentage. A detection
      rate of 75 to 100% was observed for each sampling period (age of chicken).
      Additionally, A. butzleri could not be isolated from the intestinal tract
      (jejunum, ileum, cecum, colorectum) of inoculated birds.

PMID- 14717548
TI  - Supplementation of a corn-soybean meal diet with manganese, copper, and zinc from
      organic or inorganic sources improves eggshell quality in aged laying hens.
AB  - An experiment was conducted to evaluate the effects on eggshell quality of
      supplementing the diet of laying hens with a combination of Zn, Mn, and Cu from
      organic or inorganic sources. Three groups of hens, aged 32, 60, and 69 wk were
      fed a corn-soybean basal diet containing 32.6 mg/kg Zn, 24.7 mg/kg Mn, and 4.95
      mg/kg Cu or a basal diet supplemented with 30-30-5 and 60-60-10 mg/kg of Zn, Mn,
      and Cu, respectively. Addition of Zn, Mn, and Cu in combination increased their
      concentrations in egg yolk and slightly decreased egg weight during some sampling
      from aged hens. The Zn, Cu, and Mn dietary supplementation did not affect the
      following measures of eggshell quality: percentage eggshell, eggshell index
      (shell weight per unit surface area), and eggshell stiffness. However, there was
      a small increase in elastic modulus of the eggs from one group of the older hens
      due to supplementation with Zn, Mn, and Cu. More consistently we observed
      improved breaking strength and fracture toughness (resistance to fracture) in the
      two oldest groups of hens at 1, 5, and 9 wk after introduction of the
      experimental diets. The effect was observed regardless of the source of trace
      elements.

PMID- 14717549
TI  - Evaluation of low-phytate corn and barley on broiler chick performance.
AB  - Grains produced by low-phytate barley and corn isolines homozygous for each
      species' respective low phytic acid 1-1 allele were compared to grain produced by
      near-isogenic normal or wild-type barley and corn in broiler chick feeds. Cobb x
      Cobb (384) chicks were used in a 10-d study. A randomized complete block design
      with a factorial arrangement of 2 x 2 x 3 was used with 4 replicates (8 chicks /
      replicate) per treatment. Twelve isocaloric and isonitrogenous treatment diets
      were formulated to contain 2 types of grain (barley and corn), 2 levels of grain
      (40% and 60%), and 3 sources of available P (wild-type grain, wild-type P
      supplemented grain, and low-phytate grain). Growth parameters, bone parameters,
      total bone mineral, and apparent digestibilities were measured. The mean growth
      and bone responses were 1) higher for barley diets compared to corn diets, 2)
      higher for 60% grain inclusion compared to 40%, 3) higher for low-phytate
      compared to wild-type grains, and 4) not different for low-phytate compared to P
      supplemented wild-type grain diets. Chicks fed low-phytate-based diets excreted
      33 and 43% less P than chicks fed wild-type and P-supplemented wild-type diets,
      respectively. Correlations between percentage bone ash, total bone ash, and bone
      strength indicated a strong relationship and appear to support the use of bone
      strength analysis as a simpler method than ash content determination as an
      indication of P status. Feeding low-phytate grains will reduce the need for
      supplemental P in chick diets.

PMID- 14717550
TI  - beta-Mannanase ameliorates viscosity-associated depression of growth in broiler
      chickens fed guar germ and hull fractions.
AB  - High concentrations of guar meal in broiler chicken diets reduce body weight and
      feed efficiency. The increased intestinal viscosity that is responsible for
      reduced measures of performance results from residual guar gum present in guar
      meal. Two experiments were designed to study the effects of 2 guar meal fractions
      at 3 different concentrations, germ (0, 5.0, and 7.5%) and hull (0, 2.5, and
      5.0%), and the effectiveness of a beta-mannanase at three levels (0, 1x, and 4x;
      1x = 1.09 x 10(5) units/ kg) on broiler growth and feed conversion. Growth and
      performance were measured as a function of intestinal viscosity. Addition of the
      germ fraction to rations did not reduce body weight, although feed conversion
      ratio was increased at 7.5% of the diet. Intestinal viscosity also increased
      significantly at this level. Enzyme addition significantly reduced intestinal
      viscosity. Due to an interaction that was present between hull and enzyme
      concentration, each treatment was compared separately. Inclusion of the hull
      fraction significantly reduced body weight at both levels of inclusion and
      increased feed conversion ratio at 5% inclusion. Addition of the enzyme
      significantly increased body weight and reduced feed conversion ratio in diets
      containing guar hull fractions. Supplementation of beta-mannanase to feeds
      containing either fraction of guar meal reduced intestinal viscosity and
      alleviated the deleterious effects associated with guar meal feeding.

PMID- 14717551
TI  - Effects of methionine deficiencies on plasma levels of thyroid hormones, insulin
      like growth factors-I and -II, liver and body weights, and feed intake in growing
      chickens.
AB  - We showed previously that Met deficiency at 0.25% of the diet causes elevations
      in plasma triiodothyronine (T3) in broilers. In the present study, plasma levels
      of thyroid hormones as well as insulin-like growth factors (IGF)-I and -II were
      measured in chicks fed 3 deficient levels of total Met. Control (0.5%) and Met
      deficient diets (0.4, 0.3, and 0.2%) were fed to male broilers from 8 to 22 d of
      age. Additional groups of control chicks were pair-fed with the Met-deficient
      ones. Chicks receiving 0.4% Met increased feed intake by 10% with no significant
      change in body weight. The more severe Met deficiencies of 0.3 and 0.2% caused
      graded reductions in feed intake and weight gain. However, corresponding pair-fed
      control chicks were significantly heavier. These changes suggest more marked
      alterations in metabolic processes with 0.3 and 0.2% Met than with 0.4% Met.
      Liver weights were heavier in chicks fed 0.3 and 0.2% Met but not 0.4%. Plasma T3
      was higher in all deficient chicks compared with the free-fed control, which was
      significant only with 0.3% Met. However, with 0.3 and 0.2% Met, plasma T3 was
      significantly elevated compared to pair-fed controls. Plasma thyroxine (T4) was
      lower in all deficient groups, which was significant only with 0.2% Met, whereas
      no significant differences occurred between deficient chicks and their pair-fed
      controls. Plasma IGF-I levels were not significantly different, but they were
      consistently lower in deficient chicks and deserve further study. Plasma IGF-II
      was significantly less in chicks fed 0.2% Met compared to pair-fed controls
      suggesting that Met deficiency interferes with IGF-II metabolism. We concluded
      that a deficit of dietary Met altered plasma T3 and IGF-II levels, but the effect
      was dependent on the degree of deficiency.

PMID- 14717552
TI  - Performance of broiler chicks fed various levels of dietary lysine and crude
      protein.
AB  - An experiment was conducted to establish a basal diet deficient in both protein
      and lysine. The responses of broiler chicks to graded levels of lysine at two
      levels of CP were measured in diets mixed by two experimental methods (diet
      dilution and graded supplementation). Experiment 1 had a 2 x 3 factorial
      arrangement of treatments with three dietary CP levels (17, 20, and 23%) and two
      levels of lysine per CP level (35 and 48 g lysine/kg CP). Dietary CP and lysine
      levels had significant (P < 0.001) effects on body weight gain (BWG), feed
      intake, and feed conversion ratio (FCR). In exp. 2, the lysine requirement of
      chicks (9 to 18 d of age) was estimated at two levels of CP in diets mixed by the
      diet dilution method. The requirements for lysine at 17% CP (as a percentage of
      CP) were estimated to be 4.45 +/- 0.18% for BWG (R2 = 0.83) and 4.33 +/- 0.16%
      for FCR (R2 = 0.81). Similarly, the requirements at 23% CP were 4.34 +/- 0.16%
      for BWG (R2 = 0.84) and 4.35 +/- 0.13% for FCR (R2 = 0.89). In exp. 3, the lysine
      requirement of chicks (10 to 18 d of age) was estimated at two levels of CP in
      diets mixed by the graded supplementation method. The requirements for lysine at
      18.5% CP were 5.17 +/- 0.25% for BWG (R2 = 0.80) and 4.26 +/- 0.15% for FCR (R2 =
      0.85). Similarly, the requirements at 23% CP were 4.59 +/- 0.17% for BWG (R2 =
      0.83) and 4.71 +/- 0.16% for FCR (R2 = 0.88). Results of a t-test show that the
      requirements were not significantly different between the two CP levels for BWG
      in experiments 2 and 3 (P < 0.05). It is concluded that the amino acid
      requirements of broilers are a constant proportion of CP levels at least in the
      range of CP levels commonly fed.

PMID- 14717553
TI  - Comparison of broiler performance when fed diets containing grain from YieldGard
      Rootworm (MON863), YieldGard Plus (MON810 x MON863), nontransgenic control, or
      commercial reference corn hybrids.
AB  - Two 42-d experiments compared the nutritional value of YieldGard Rootworm corn
      (MON863; experiment 1) and YieldGard Plus corn (MON810 x MON863; experiment 2) to
      their respective nontransgenic controls and 6 commercial reference corn hybrids
      when fed to growing broilers. For each experiment, a randomized complete block
      design was used with 8 dietary treatments in each of 5 replicated blocks of pens.
      In experiment 1, no differences among diets were observed (P > 0.05) for final
      live weights and feed conversion. Broilers fed diets containing MON863 corn had
      adjusted feed conversion similar to the nontransgenic control and the population
      of control and commercial diets. On a weight basis, there were no differences
      among diets for chill, fat pad, and thigh, drum, and wing weights. Differences (P
      < 0.05) between MON863 and commercial corn diets were noted for breast meat,
      chill and thigh, drum, and wing weights on a percentage of weight basis. No
      differences were observed (P > 0.05) in the percentage of moisture, protein, and
      fat in breast meat or thigh meat across treatment diets. In experiment 2, there
      were no significant differences among diets for all broiler performance and
      carcass parameters evaluated. Broilers overall performed consistently and had
      similar carcass yields and meat compositions when fed diets containing MON863
      corn or MON810 x MON863 corn as compared with their respective nontransgenic
      control and commercial diets, supporting a conclusion of similar feeding values
      among diets.

PMID- 14717554
TI  - Pulmonary artery vasoactivity in broiler and Leghorn chickens: an age profile.
AB  - Vascular function plays a preponderant role in the pulmonary changes that occur
      with maturation, during birth, and in the development of pulmonary hypertension.
      This study was designed to characterize the changes in vasoactivity occurring in
      broiler and Leghorn chickens from late embryonic life to 5 wk of age. Pulmonary
      arteries were isolated from 19- and 20-d-old embryos, hatchlings, and 1-, 2-, 3-,
      4- and 5-wk-old chickens of both lines and subjected to KCl (45.4 mM)- and
      endothelin-1 (10(-7.5) M)-induced vasoconstrictions followed by acetylcholine
      (ACh; 10(-5), 10(-6) and 10(-7) M)- and papaverine (10(-4) M)-induced
      vasodilations. Vasoconstrictions were greatest at hatch and rapidly declined
      thereafter, whereas vasodilations were greatest in 20-d-old embryos except with
      10(-7) M ACh. Broilers grew faster than Leghorns and had lower vasodilation
      responses to all concentrations of ACh at 2 and 5 wk of age. Broilers also had
      greater right-to-total ventricular weight ratios at 5 wk of age, whereas ratios
      were greater in Leghorn embryos at 20 d of incubation and at hatch. Thus, for a
      brief period before hatch there is a significant increase in pulmonary
      endothelium-dependent vasodilation capacity in the chicken embryo, which may aid
      in the transition from chorioallantoic to pulmonary respiration. The absence of
      differences in vasodilator capacity between broilers and Leghorns before hatch
      suggests that the differences in pulmonary artery relaxation capacity and
      pulmonary hypertension observed after hatch in broilers are not necessarily
      acquired during incubation but may be related to rapid growth of the broiler
      chicken.

PMID- 14717555
TI  - The expression of calbindin in chicks that are divergently selected for low or
      high incidence of tibial dyschondroplasia.
AB  - Three experiments were conducted with broiler chicks that were divergently
      selected for low or high incidence of tibial dyschondroplasia (LTD and HTD,
      respectively) to determine if the expression of intestinal calbindin-28 kD mRNA
      and protein differed between the 2 strains. In addition, levels of intestinal
      vitamin D receptor mRNA and plasma thyroid hormone concentrations were also
      examined. In experiment 1, LTD and HTD chicks were fed a corn-soybean meal diet
      that was adequate in all nutrients except cholecalciferol (D3), which was
      titrated to 5 or 40 microg/kg diet in a completely randomized 2 x 2 factorial
      arrangement. At 4 and 8 d of age, HTD chicks fed 5 microg of D3/kg of diet had a
      lower (P < 0.05) expression level of calbindin-28 kD mRNA than the LTD chicks fed
      the same diet. At 4 and 8 d of age, HTD chicks fed 5 microg of D3 had the lowest
      intestinal expression of calbindin-28 kD protein. Expression of vitamin D
      receptor mRNA did not differ for broiler strains at either level of D3
      supplementation. In experiment 2, there was no significant difference in the
      expression of calbindin-28 kD mRNA or vitamin D receptor mRNA between day-of
      hatch LTD, HTD, and commercial broiler chicks. Experiment 3 was similar in design
      to the first experiment except that the birds were fed for 18 d. Calbindin-28 kD
      and vitamin D receptor mRNA expression levels at 18 d were similar to those
      observed in experiment 1. Plasma triiodothyronine and free-triiodothyronine
      concentrations were greater for LTD chicks, regardless of dietary D3
      supplementation levels. These results suggest that divergent selection of
      broilers for LTD or HTD alters the physiological response to nutritionally
      inadequate levels of dietary D3.

PMID- 14717556
TI  - Effects of turning duration during incubation on corticosterone and thyroid
      hormone levels, gas pressures in air cell, chick quality, and juvenile growth.
AB  - Two peaks of embryo mortality have been identified during incubation of chicken
      eggs (the first and the final phases of incubation), and both are linked to egg
      turning. Turning in the first week enables proper formation of extra-embryonic
      membrane and in the final week avoids embryo malpositioning. The hatchability of
      the eggs, however, may depend on physiological parameters (e.g., hormone levels
      or gas pressures) that turning may influence to ensure proper embryo development
      and survival. It is not clear how long turning should continue during this second
      phase to ensure these conditions, but it is general practice to turn eggs until
      18 d. This study describes the effects of turning chicken eggs for different
      durations during the last days of incubation on embryo physiological parameters
      that may be linked to embryo survival, hatchability, and broiler posthatch
      performance. Cobb eggs were incubated for 21 d under standard incubation
      conditions but with varying turning durations. Eggs were turned until 12, 15, or
      18 d and left in a horizontal position until transferred to hatcher baskets on
      the 19th day. Blood samples from embryos were analyzed for corticosterone at d
      15, d 18, internal pipping (IP), and hatch. Triiodothyronine (T3) and thyroxine
      (T4) were measured at IP and at hatch. Partial pressures of CO2 (pCO2) and O2
      (PO2) in the air cell were measured at d 18 and at IP stage. Hatchability of
      fertile eggs, incubation duration, weights of 1-d-old chicks, chick quality, and
      their growth potential determined as absolute weight and relative growth (RG) to
      d 7 were recorded. Corticosterone levels increased in all treatments with embryo
      age until hatch, but there were no significant differences among treatments. Eggs
      turned until 18 d had higher pCO2 and lower PO2 at IP than those turned for 12 or
      15 d. T3 and T4 were higher at IP in eggs turned for 18 d compared with the other
      two groups in which T3 and T4 were not different. T3/T4 ratio in 1-d-old chicks
      was also lower in eggs turned until 18 d. Incubation duration, and weights of 1-d
      old chicks were similar for all treatments groups. Hatchability and percentage of
      high quality chicks were lower for eggs turned for 15 d compared to the 2 other
      groups, which were not different. However, 7-d-old weights and RG decreased with
      increasing duration of egg turning. We concluded that although turning until 18 d
      benefited hatchability and chick quality, it depressed potential posthatch
      performance of the chick to 7 d of age.

PMID- 14717557
TI  - Biochemical analyses of muscles from poultry bred for rapid growth.
AB  - In the current study, commercial broiler breeder hens were mated with either
      commercial broiler breeder males (B/B) or artificially inseminated with semen
      from Leghorn cockerels (B/L). Embryos and chicks from each mating were used to
      study the effects of paternal genotype on breast muscle myosin expression without
      the confounding effects of differences in egg size and embryo development due to
      maternal genotype. Specifically, the temporal transitions of myosin heavy chain
      (MyHC) isoforms within the pectoralis (P.) major and P. minor were measured. The
      relative concentration of the embryonic MyHC isoform increased from d 17 through
      21 in ovo in both genotypes and was higher in B/B embryos than in B/L embryos (P
      < or = 0.01). At 21 d posthatch, there was an increased proportion of the adult
      MyHC isoform within the P. major and P. minor in B/B compared with B/L chicks (P
      < or = 0.01). This result suggests that the B/B chicks were making the transition
      to mature skeletal muscle more rapidly than the B/L chicks. Although samples
      taken from the P. minor of B/B and B/ L chicks exhibited an increased proportion
      of the adult MyHC isoform and lower proportion of the neonatal MyHC isoform at 21
      d, the genetic differences were far more pronounced in the larger P. major (P <
      or = 0.01). In summary, the P. major from the faster growing B/B chicks exhibited
      earlier temporal transitions of developmental fast MyHC, and these differences
      were evident as early as 17 d in ovo.

PMID- 14717558
TI  - Influence of photoperiod and age of photostimulation on the incidence of
      polycystic ovarian follicle syndrome in turkey breeder hens.
AB  - An arrest in egg laying associated with a polycystic ovarian follicle syndrome
      (PCOF) has been recently reported early in the egg production period in turkey
      hens photostimulated at 30 wk of age (WOA) with continuous light. When autopsied
      2 to 3 wk after laying ceased, the ovaries of PCOF hens contained an increased
      number of mature size (F1) yolky follicles in comparison with normally laying
      hens plus several larger cystic follicles, while their oviducts were equal in
      weight to oviducts of hens laying normally. Four experiments were conducted to
      examine effects of age at photostimulation and photoperiod [14L:10D (14L) or
      continuous lighting 24L:0D (24L)] on the incidence of the PCOF syndrome. Turkey
      hens of the egg line were given short-day photostimulation of 6L:18D at 16 WOA
      and then photostimulated with either 14L or 24L at various ages between 26 to 70
      WOA. Egg production was followed for 6 to 8 wk, and hens that stopped laying eggs
      during this period were autopsied 2 to 3 wk later to determine presence and
      incidence of the PCOF syndrome. At 26 WOA, the PCOF incidence was 80% with 24L
      lighting and 31% with 14L lighting (P = 0.006). At 28 WOA, the PCOF incidence was
      56% with 24L lighting and 25% with 14L lighting (P = 0.072). At 31, 34, and 41
      WOA, there were no differences (P > or = 0.10) in incidence of the PCOF syndrome
      between the 24L and 14L treatments. Within the 24L treatment, the PCOF incidence
      at 26 and 28 WOA (80 and 56%) were greater than at 31 WOA and older ages (< or =
      20%; P < or = 0.025). Within the 14L lighting treatment, the PCOF incidence was
      not different among ages (26 WOA, 31% to 48 WOA, 0%; P > or = 0.05). It was
      concluded that the incidence of the PCOF syndrome is greater when photosensitive
      Egg line turkey hens are photostimulated at relatively young ages (less than
      31WOA) and with 24L in comparison to 14L lighting.

PMID- 14717559
TI  - Breast meat quality and composition in unique chicken populations.
AB  - The objective of this project was to examine the diversity of breast meat
      composition and quality traits among unique resource populations. Birds from 5
      groups (inbred Leghorn, inbred Fayoumi, commercial broilers, F5 broiler-inbred
      Leghorn cross, and F5 broiler-inbred Fayoumi cross) were utilized. Contemporary
      stocks (broilers, inbreds, and crosses) were grown in a single house but in
      separate pens. Birds were harvested at 8 wk of age. Breast muscle weight,
      moisture, lipid and protein contents, color, pH, and Kramer shear force values
      were determined on birds from each group. Breasts from broilers contained lower
      percentages of protein (P < 0.05) and greater percentages of lipid (P < 0.05)
      compared with all other groups. The 5 genetic stocks did not differ for Hunter L
      values or pH. The data indicate that the Leghorn inbred line breasts were a more
      pure and more intense red color than the crossbred contemporary (P < 0.05).
      Kramer shear force (kg/g sample) was higher (P < 0.05) in breasts from broilers
      than in breasts from the inbred lines. Our results demonstrate that the 5 genetic
      groups differed markedly in breast meat composition and quality characteristics.
      The described outbred by inbred advanced intercross lines will be useful in
      searches for genes affecting meat quality traits. Definition of the molecular
      factors that influence these traits will enhance our ability to make improvements
      in composition and quality of poultry meats.

PMID- 14717560
TI  - Presence of Campylobacter inthe respiratory tract of broiler carcasses before and
      after commercial scalding.
AB  - Campylobacter could be detected in the thoraco-abdominal cavity of broiler
      carcasses even if they were carefully eviscerated by hand with no evidence of
      intestinal rupture or leakage. If Campylobacter is present in the air sacs, which
      are unavoidably torn during evisceration, it could contaminate the thoraco
      abdominal cavity of the eviscerated carcass. This study was done to determine if
      Campylobacter contamination is present in the respiratory tract of broilers prior
      to evisceration. Whole carcass rinses and respiratory tract washes were done on
      broiler carcasses collected at a commercial processing plant just before and just
      after scalding. Samples were cultured for presence and numbers of Campylobacter,
      Escherichia coli, coliforms, and total aerobic bacteria. Campylobacter isolates
      were subtyped by sequencing the short variable region of the flaA gene. The same
      subtypes of Campylobacter were detected in whole carcass rinse samples as in
      respiratory tract wash samples from individual broilers. Furthermore, the same
      numbers and subtypes of Campylobacter were recovered from respiratory tracts of
      carcasses collected before scalding and those collected after scalding. However,
      respiratory tracts of carcasses after scalding had higher numbers of E. coli,
      coliforms, and total aerobic bacteria than those tested before scalding. Although
      some bacterial counts were higher in the respiratory tracts of carcasses after
      scalding, Campylobacter counts were not. It appears that Campylobacter is present
      in the respiratory tracts of broilers as they enter processing, and contamination
      may be due to airborne bacteria during production or transport.

PMID- 14717561
TI  - Filling and emptying of the alimentary tract of meal-fed broiler breeder hens.
AB  - For evaluation of the filling and emptying of the alimentary tract, broiler
      breeder hens were cooped and processed over a 2-d period. Hens were fed at 0600 h
      on d 1 and after access to feed for 0, 2, 4, and 6 h were placed into coops. Half
      of the hens from each pen were either immediately processed or were held in coops
      over-night and processed the following morning, d 2. The alimentary tract was
      excised from the carcass and then separated and weighed in three segments: the
      crop, proventriculus and gizzard, and intestines. Hens processed on d 1, after
      access to feed for only 2 h, had attained maximum intestine weight (176 g), but
      not until after access to feed for 6 h were peak crop weight (95 g) and peak
      weight for the proventriculus and gizzard (78 g) attained. Hens processed on d 2
      did not differ in crop (12 to 14 g) or intestine (140 to 162 g) weight, but
      proventriculus and gizzard weights were significantly lower for hens not fed on d
      1 prior to cooping (54 g) compared with hens fed on d 1 and cooped after 2, 4, or
      6 h (62 to 63 g). However, hens processed on d 2 had proventriculus and gizzard
      weights that were the same as for those hens processed on d 1 and cooped at 0 h
      (63 g). Clearance of ingesta from the crop, proventriculus and gizzard, and
      intestines readily occurred while hens were held overnight without access to
      water.

PMID- 14717562
TI  - Inequity in health: let's not live with it.

PMID- 14717563
TI  - A framework linking community empowerment and health equity: it is a matter of
      CHOICE.
AB  - This paper presents a framework to explore the relationship between health equity
      and community empowerment. It traces the progression of the concept of
      participation to the present term of empowerment and the links among empowerment,
      equity, and health outcomes. It argues that the relationship can best be
      described by using the acronym CHOICE (Capacity-building, Human rights,
      Organizational sustainability, Institutional accountability, Contribution, and
      Enabling environment). Based on the concept of development as freedom put forward
      by Nobel Laureate Amartya Sen, the paper describes how each factor illustrates
      the relationship between equity and empowerment in positive health outcomes,
      giving appropriate examples. In conclusion, it is suggested that these factors
      might form the basis of a tool to assess the relationship between equity and
      empowerment and its impact on health outcomes.

PMID- 14717564
TI  - Monitoring equity in health and healthcare: a conceptual framework.
AB  - This paper aims at articulating a conceptual framework for monitoring equity in
      health and healthcare. The focus is on four main questions: What is health
      equity? What is monitoring? What are the essential components of a system for
      monitoring health equity? and Why monitor health equity? Monitoring equity in
      health and healthcare requires comparing indicators of health and its social
      determinants among social groups with different levels of underlying social
      advantage, i.e. groups who occupy different positions in a social hierarchy. A
      framework is presented for formulating the key questions, defining the social
      groups to be compared, and selecting the health indicators and measures of
      disparity that are fundamental to monitoring health equity. Although monitoring
      health equity is a scientific endeavour, its fundamental objective is guided by
      values; technical challenges should be addressed as part of a broader strategy to
      confront the political obstacles to greater equity.

PMID- 14717565
TI  - Immunization divide: who do get vaccinated in Bangladesh?
AB  - This paper examines inequalities in the use of, and access to, vaccination
      service in Bangladesh by analyzing national and small area-based datasets. The
      analysis showed that female children had a lower immunization coverage than male
      children--the difference persists for all antigens and widens against girls for
      higher doses. The immunization coverage was higher for children whose mothers
      were more educated. Children whose fathers had a higher-status occupation
      (salaried employment) were two-and-a-half times more likely to be immunized than
      children whose fathers held a lower-status job, e.g. day-labourer. The coverage
      for the poorest quintile was 70% of the well-to-do. Children residing in urban
      areas were more likely to be fully immunized than their rural counterparts (70%
      vs 59% for children aged 12-23 months). Within urban areas, the situation in
      slums was worse. Large differences existed among the various administrative
      regions of the country. Ethnic minorities in the Chittagong Hill Tracts had a
      lower immunization coverage than the Bangalees. In Sylhet, children of non-local
      workers in Bangladesh-owned tea estates had a lower coverage than their
      counterparts in foreign-owned tea estates. The study identifies children of
      various disadvantaged groups as having a lower coverage. Managers of immunization
      programmes must realize that only through removal of such disparities among
      groups will overall coverage be increased. Affirmative actions in targeting could
      be effective in reaching such groups.

PMID- 14717566
TI  - Equity in self-reported adult illness and use of health service in South Africa:
      inter-temporal comparison.
AB  - The study was carried out to assess the magnitude of, and change in, inequities
      in self-reported adult illness and use of healthcare and to consider the policy
      implications of the findings. Datasets from three household surveys carried out
      in 1993, 1995, and 1998 were used. Inequities were measured using illness and
      healthcare-use concentration indices. Self-reported adult illness was greater
      among the rich in 1993, but this was reversed to reflect higher levels of
      reported illness among the poor in 1995 and 1998. Inequities were observed in
      self-reported injury and disability/chronic illness that favour the rich. The
      poor also reported more days of sickness compared to the rich. Overall, there
      were higher levels of use of doctors and hospital services by the rich, relative
      to their levels of reported illness. In contrast, there was a greater use of
      public-sector facilities by the poor. The time taken to reach a health facility
      also had a bias in favour of the rich. Although there were some favourable
      changes in the levels of inequities between the three time periods, there still
      remained considerable inequities that favoured the rich in self-reported adult
      illness and use of health services that need to be addressed. The consequences of
      higher concentration of chronic illness/disability and injury among the poor have
      far-reaching negative consequences on the socioeconomic welfare of the
      individuals and households. Redressing these inequities needs a holistic strategy
      that transcends the health sector.

PMID- 14717567
TI  - Medical expenditure and rural impoverishment in China.
AB  - Thanks to continued economic growth and increasing income, the overall poverty
      rate has been on the decline in China. However, due to escalating medical costs
      and lack of insurance coverage, medical spending often causes financial hardship
      for many rural families. Using data from the 1998 China National Health Services
      Survey, the impact of medical expenditure on the poverty headcount for different
      rural regions was estimated. Based on the reported statistics on income alone,
      7.22% of the whole rural sample was below the poverty line. Out-of-pocket medical
      spending raised this by more than 3 percentage points. In other words, medical
      spending raised the number of rural households living below the poverty line by
      44.3%. Medical expenditure has become an important source of transient poverty in
      rural China.

PMID- 14717568
TI  - Healthcare-financing reforms in transitional society: a Shanghai experience.
AB  - Since the 1950s, China has had a very wide coverage of healthcare service at the
      local level. In urban areas, the employment-based healthcare-insurance schemes
      (Government Insurance Scheme and Labour Insurance Scheme) worked hand in hand
      with the full employment policy of the Government, which guaranteed basic care
      for almost every urban resident. However, since the economic reforms of the early
      1980s, China's healthcare system has met great challenges. Some came from the
      reform of the labour system, and other challenges came from the introduction of
      market forces in the healthcare sector. The new policy of the Chinese Government
      on the Urban Employees' Basic Health Care Insurance is to introduce a cost
      sharing plan in urban China. Like other major social policy changes, this new
      health policy also has a great impact on the lives of the Chinese people.
      Affordability has been the major concern among urban residents. Shanghai
      implemented the cost-sharing healthcare policy in the spring of 2001. It may be
      too early to assess the pros and cons of the new policy, but evidence shows that
      the employment-based health-insurance scheme excludes those at high risk and in
      most need. It is argued that the cost-sharing healthcare system will limit access
      by some people, especially those who are most vulnerable to the consequences of
      ill health and those in low-income groups, unless the deductibles vary according
      to income and unless low-income groups are exempt from paying premiums and
      deductibles.

PMID- 14717569
TI  - A wealth index to screen high-risk families: application to Morocco.
AB  - This study defined a wealth index that was strongly correlated with a health
      indicator: the survival of children aged less than five years. This index allowed
      the most vulnerable social groups for health outcomes to be identified. These
      groups could become the target for focused interventions and in particular for
      health-insurance schemes. The study was based on a thorough analysis of data
      collected in Morocco in the 1992 Demographic and Health Survey (DHS). Results of
      the analysis showed that a simple score based on 15 socioeconomic indicators
      provided a proper discriminatory tool for screening families at higher risk of
      infant and child mortality. The score was based on characteristics of housing and
      household goods which are easy to collect in the field. The scoring system was
      shown to be as powerful as more complex statistical techniques, such as
      discriminant analysis. It could be used for determining who could be eligible for
      free health insurance.

PMID- 14717570
TI  - Examining health equity through satisfaction and confidence of patients in
      primary healthcare in the Republic of Trinidad and Tobago.
AB  - Surveys of patient satisfaction are widely used for identifying priorities and
      problems in healthcare reforms. The present study examined satisfaction and
      confidence of patients in public healthcare in Trinidad and Tobago. Data were
      gathered by interviewing a random sample (n = 280) of primary healthcare (PHC)
      patients. Level of patient satisfaction was high but not constant. Results of
      interviews showed that patients with a higher monthly income (p = 0.032) and
      patients who most recently used private medical care (p = 0.037) had lower levels
      of satisfaction with health services. Employment had an effect on satisfaction (p
      = 0.065), significant among patients who had recently accessed private medical
      care (p = 0.039). Patients using PHC clinics preferred private care to public
      care. Confidence in public care decreased with increasing complexity of the
      medical condition. These preliminary results support continued efforts in health
      sector reforms and call for the enhancement of data on satisfaction through more
      comprehensive qualitative data-collection methods.

PMID- 14717572
TI  - Mechanisms of racial inequalities in prevalence of diarrhoea in South Africa.
AB  - Decades of apartheid policies have resulted in marked racial inequalities in
      health in South Africa. The black:white rate ratio of diarrhoea among children
      aged less than five years, one of the five most common causes of infant and child
      deaths, stood at 6.5 in 1998. Using data from the 1998 South African Demographic
      and Health Survey, this paper examines the mechanisms of this racial disparity.
      The research confirms the presence of persistent racial inequalities in access to
      safe drinking-water and sanitation and in maternal education and household
      wealth, with the black population constituting the most disadvantaged group.
      While the living environment and access to safe drinking-water explain the
      excessive risk of diarrhoea among the black population compared to the coloured
      and Indian populations, the excessive risk of diarrhoea among the black
      population compared to the white population cannot be explained by disparities in
      the living environment, hygiene levels, and socioeconomic factors.

PMID- 14717571
TI  - Incident HIV infection among men attending STD clinics in Pune, India: pathways
      to disparity and interventions to enhance equity.
AB  - Systematic disparities in rates of HIV incidence by socioeconomic status were
      assessed among men attending three sexually transmitted disease (STD) clinics in
      Pune, India, to identify key policy-intervention points to increase health
      equity. Measures of socioeconomic status included level of education, family
      income, and occupation. From 1993 to 2000, 2,260 HIV-uninfected men who consented
      to participate in the study were followed on a quarterly basis. Proportional
      hazards regression analysis of incident HIV infection identified a statistically
      significant interaction between level of education and genital ulcer disease.
      Compared to the lowest-risk men without genital ulcer disease who completed high
      school, the relative risk (RR) for acquisition of HIV was 7.02 (p < 0.001) for
      illiterate men with genital ulcer disease, 3.62 (p < 0.001) for men with some
      education and genital ulcer disease, and 3.02 (p < 0.001) for men who completed
      high school and had genital ulcer disease. For men with no genital ulcer disease
      and those with no education RR was 1.09 (p = 0.84), and for men with
      primary/middle school it was 1.70 (p = 0.03). The study provides evidence that by
      enhancing access to treatment and interventions that include counselling,
      education, and provision of condoms for prevention of STDs, especially genital
      ulcer disease, among disadvantaged men, the disparity in rates of HIV incidence
      could be lessened considerably. Nevertheless, given the same level of knowledge
      on AIDS, the same level of risk behaviour, and the same level of biological co
      factors, the most disadvantaged men still have higher rates of HIV incidence.

PMID- 14717573
TI  - Global Equity Gauge Alliance: reflections on early experiences.
AB  - The paper traces the evolution and working of the Global Equity Gauge Alliance
      (GEGA) and its efforts to promote health equity. GEGA places health equity
      squarely within a larger framework of social justice, linking findings on
      socioeconomic and health inequalities with differentials in power, wealth, and
      prestige in society. The Alliance's 11 country-level partners, called Equity
      Gauges, share a common action-based vision and framework called the Equity Gauge
      Strategy. An Equity Gauge seeks to reduce health inequities through three broad
      spheres of action, referred to as the 'pillars' of the Equity Gauge Strategy,
      which define a set of interconnected and overlapping actions. Measuring and
      tracking the inequalities and interpreting their ethical import are pursued
      through the Assessment and Monitoring pillar. This information provides an
      evidence base that can be used in strategic ways for influencing policy-makers
      through actions in the Advocacy pillar and for supporting grassroots groups and
      civil society through actions in the Community Empowerment pillar. The paper
      provides examples of strategies for promoting pro-equity policy and social change
      and reviews experiences and lessons, both in terms of technical success of
      interventions and in relation to the conceptual development and refinement of the
      Equity Gauge Strategy and overall direction of the Alliance. To become most
      effective in furthering health equity at both national and global levels, the
      Alliance must now reach out to and involve a wider range of organizations,
      groups, and actors at both national and international levels. Sustainability of
      this promising experiment depends, in part, on adequate resources but also on the
      ability to attract and develop talented leadership.

PMID- 14717574
TI  - Review of North-South and South-South cooperation and conditions necessary to
      sustain research capability in developing countries.
AB  - The paper extracted pertinent aspects of 21 years (1981-2001) of scientific
      cooperation among Zimbabwe's Blair Research Laboratory (BRL), the Biomedical
      Research and Training Institute (BRTI), and the Danish Bilharziasis Laboratory
      (DBL). DBL supported the building of research capacity at BRL through PhD-level
      training and short courses on research training organized by BRTI. The BRL-BRTI
      DBL cooperation involved institutional support, scientific training, joint
      research programmes, and technology transfer, and forms a basis for the
      discussion of North-South and South-South collaboration in this paper. As the
      collaboration matured, DBL researchers began cooperating with their counterparts
      at BRL in internationally funded research programmes and partnerships based on
      mutual interests and responsibilities. Several research projects were formulated
      under co-principal investigators from the two institutions and later extended to
      other European and US institutions. An impressive outturn (18 PhDs) of
      postgraduate students undertaking field-based PhD work was accomplished from 1990
      to 2001. As the socioeconomic situation in Zimbabwe deteriorated from 1999,
      significant attrition of senior scientists began to affect some of BRL's core
      functions in support of the Ministry of Health's programmes. In solidarity with
      BRL, DBL and BRTI jointly implemented a management-strengthening project to
      reduce deterioration of research productivity by retaining mid-level research
      managers. BRTI, able to respond rapidly to research needs in the Southern Africa
      Development Community (SADC), is not in competition with national research
      institutions and universities. An advisory committee of SADC stakeholders sets
      its priorities. The framework for South-South cooperation is research training to
      facilitate national scientists to attract resources from local and international
      funding agencies. It has established a National Institutes of Health-accredited
      ethical review board that provides ethical assurance for BRTI and non-BRTI
      administered projects. Over the last eight years, BRTI has established regional
      and international legitimacy, and many funding agencies accept the role of the
      organization in 'Third Country Training for South-South Cooperation'. The article
      concludes by identifying essential conditions for sustaining research capability
      at BRL and similar institutions in developing countries. In rolling out a new
      ethos for research, great expectation is placed on the success of the New
      Partnership for Africa Development.

PMID- 14717575
TI  - Screening and brief intervention for alcohol problems among college students
      treated in a university hospital emergency department.
AB  - The authors evaluated a protocol to screen and provide brief interventions for
      alcohol problems to college students treated at a university hospital emergency
      department (ED). Of 2,372 drinkers they approached, 87% gave informed consent. Of
      those, 54% screened positive for alcohol problems (Alcohol Use Disorders
      Identification Test score < or = 6). One half to two thirds of the students who
      screened positive drank 2 to 3 times a week, drank 7 or more drinks per typical
      drinking day, or had experienced alcohol dependence symptoms within the past
      year. Ninety-six percent of screen-positive students accepted counseling during
      their ED visit. Three quarters of those questioned at 3-month follow-up reported
      that counseling had been helpful and that they had decreased their alcohol
      consumption. The prevalence of alcohol problems, high rates of informed consent
      and acceptance of counseling, and improved outcomes suggest that the ED is an
      appropriate venue for engaging students at high risk for alcohol problems.

PMID- 14717576
TI  - Trends in marijuana and other illicit drug use among college students: results
      from 4 Harvard School of Public Health College Alcohol Study surveys: 1993-2001.
AB  - The authors examined changes in college students' illicit drug use, patterns of
      polydrug use, and the relationship between students' ages of initiation of
      substance use and later use of marijuana and other illicit drugs between 1993 and
      2001. Data from 119 US colleges and universities in the Harvard School of Public
      Health College Alcohol Study were used in the study. They found significant
      increases in percentages of students' use of marijuana in the past 30 days (from
      13% to 17%), past year (from 23% to 30%), and lifetime (from 41% to 47%) between
      1993 and 2001, with most of the increase occurring between 1993 and 1997. Past 30
      day use of other illicit drugs increased from 4% to 7% and past year use
      increased from 11% to 14%. More than 98% of marijuana and other illicit drug
      users used another substance. They also either smoked, were binge drinkers,
      and/or were users of another illicit drug. Drug prevention programs should
      emphasize heavy alcohol use and smoking and should start when students are in
      high school or earlier.

PMID- 14717577
TI  - Eating dysfunctions in college women: the roles of depression and attachment to
      fathers.
AB  - The authors examined the roles of depression and attachment to fathers in college
      women's eating dysfunctions. Three-hundred six undergraduate women completed (1)
      a diagnostic measure of eating dysfunctions that categorized them as
      asymptomatic, symptomatic but not eating disordered, or eating disordered; (2) 3
      dimensional measures of attachment to fathers; and (3) a dimensional measure of
      depression. Depression was directly related to severity of participants' eating
      dysfunction; the eating-disordered group had scores consistent with clinical
      depression. After controlling for depression, 3 facets of attachment to fathers
      significantly differentiated the 3 groups.

PMID- 14717578
TI  - Using a social marketing approach to advertise Sexual Assault Nurse Examination
      (SANE) services to college students.
AB  - The authors report on an advertising campaign to communicate the availability and
      desirability of using Sexual Assault Nurse Examination (SANE) services. They used
      social marketing precepts to develop posters to educate college students about
      using SANE as a health service and as an arm of prosecution. After 2 advertising
      campaigns, they conducted an anonymous survey of 1,051 college students. The
      findings indicated that posters placed in residence halls and public bathrooms
      reached students, produced a statistically significant increase in students'
      understanding of SANE services, and were significantly associated with their
      hypothetical encouragement of others to use SANE. Gender mediated some results.
      Posters placed in private viewing spaces were found to be a viable way to
      communicate information about SANE. Funding to combat violence against women on
      campus should be aimed at increasing students' access to SANE and should include
      the costs of advertising the program.

PMID- 14717579
TI  - The impact of educational efforts on first-year university students' acceptance
      of meningococcal vaccine.
AB  - The authors measured the impact of educational efforts on the number of college
      students who received meningococcal vaccine. First-year Brown University students
      from the classes of 2004 (n = 1,562) and 2005 (n = 1,518) received educational
      vaccine materials before they arrived on campus, whereas students from the class
      of 2003 (n = 1.441) did not. Students in the class of 2003, 13% (n = 184) of whom
      had received vaccine before their arrival on campus, served as the baseline.
      These educational efforts by the college health services before students arrived
      on campus increased the number of students immunized before campus arrival to 46%
      (n = 724) for the class of 2004, and 60% (n = 913) for the class of 2005.
      Education about the benefits of meningococcal vaccine before students' arrival on
      campus increased both the number of immunized students and the overall
      immunization rate among students.

PMID- 14717580
TI  - Binge drinking: not the word of choice.
AB  - Educators and researchers strive to use terms that reflect a replicable measure
      of behavior. A term commonly used to describe drinking of a problematic nature is
      binge drinking. Binge drinking defines behavior by a number of drinks of an
      alcoholic beverage consumed in a space of time. The authors argue that the term
      does not describe drinking behavior that students believe is problematic. They
      claim that students define problem drinking not in terms of quantity, but rather
      by the outcome (and occasionally by frequency), and attribute different negative
      connotations to the term binge. They suggest using a term that has shared meaning
      with students, such as dangerous drinking, to describe the drinking behavior that
      results in undesirable or unintended consequences.

PMID- 14717581
TI  - Assisted workouts: starting my own workout program.
AB  - As an undergraduate student with cerebral palsy, I found it difficult to achieve
      my goal of starting a regular exercise program at my school, the University of
      Central Florida. However, when I started a program called Assisted Workouts in
      spring 2003. the struggle proved to be well worth it. The program is not only
      beneficial to me, but it has also opened the door for other students who, because
      of disability or injury, need assistance in using gym equipment.

PMID- 14717582
TI  - A minimal kinetic model for a viral DNA packaging machine.
AB  - Terminase enzymes are common to both eukaryotic and prokaryotic double-stranded
      DNA viruses. These enzymes possess ATPase and nuclease activities that work in
      concert to "package" a viral genome into an empty procapsid, and it is likely
      that terminase enzymes from disparate viruses utilize a common packaging
      mechanism. Bacteriophage lambda terminase possesses a site-specific nuclease
      activity, a so-called helicase activity, a DNA translocase activity, and multiple
      ATPase catalytic sites that function to package viral DNA. Allosteric
      interactions between the multiple catalytic sites have been reported. This study
      probes these catalytic interactions using enzyme kinetic, photoaffinity labeling,
      and vanadate inhibition studies. The ensemble of data forms the basis for a
      minimal kinetic model for lambda terminase. The model incorporates an ADP-driven
      conformational reorganization of the terminase subunits assembled on viral DNA,
      which is central to the activation of a catalytically competent packaging
      machine. The proposed model provides a unifying mechanism for allosteric
      interaction between the multiple catalytic sites of the holoenzyme and explains
      much of the kinetic data in the literature. Given that similar packaging
      mechanisms have been proposed for viruses as dissimilar as lambda and the herpes
      viruses, the model may find general utility in our global understanding of the
      enzymology of virus assembly.

PMID- 14717583
TI  - Analysis of the molecular interaction of the farnesyl moiety of transducin
      through the use of a photoreactive farnesyl analogue.
AB  - Farnesylation of the gamma-subunit of the retinal G-protein, transducin
      (Talpha/Tbetagamma), is indispensable for light-initiated signaling in
      photoreceptor cells. However, the farnesyl-mediated molecular interactions
      important for signaling are not well understood. To explore this issue, we
      created a functional Tbetagamma analogue in which the farnesyl group was replaced
      with a (3-azidophenoxy)geranyl (POG) group, a novel farnesyl analogue with a
      distal photoreactive azido group. In the presence of lipid membranes and/or
      Talpha-GDP, UV irradiation of POG-modified Tbetagamma (POG-Tbetagamma) invariably
      yielded a cross-linked product Tgamma-Tbeta, reflecting a constitutive
      interaction of the Tgamma C-terminal lipid with Tbeta. In addition to the Tgamma
      Tbeta adduct, a Tgamma-Talpha cross-link was detected in the aqueous fraction.
      Reconstitution of POG-Tbetagamma with Talpha and light-activated rhodopsin (Rh)
      in photoreceptor membranes resulted in cross-linking of Tgamma with a
      glycerophospholipid, indicating molecular interaction of the farnesyl group with
      cellular membranes. The Tgamma-phospholipid cross-link was observed only in the
      presence of both Talpha-GDP and Rh, and was abolished by the addition of
      GTPgammaS or by replacing Rh with opsin. These findings suggest a transient
      farnesyl-membrane interaction occurs only in a signaling state formed in a
      transducin-Rh ternary complex. On the other hand, UV irradiation of POG
      Tbetagamma in a soluble complex with phosducin, a negative regulator of G
      protein, yielded a Tgamma-phosducin adduct in addition to the Tgamma-Tbeta cross
      link. These results illustrate that, rather than being a static membrane anchor,
      the farnesyl moiety plays an active role in the dynamics of protein-protein and
      protein-membrane interactions at defined steps in the signal transduction
      process.

PMID- 14717584
TI  - Phosphatidylserine binding sites in erythroid spectrin: location and implications
      for membrane stability.
AB  - The erythrocyte membrane is a composite structure consisting of a lipid bilayer
      tethered to the spectrin-based membrane skeleton. Two complexes of spectrin with
      other proteins are known to participate in the attachment. Spectrin has also been
      shown to interact with phosphatidylserine (PS), a component of the lipid bilayer,
      which is confined to its inner leaflet. That there may be multiple sites of
      interaction with PS in the spectrin sequence has been inferred, but they have not
      hitherto been identified. Here we have explored the interaction of PS-containing
      liposomes with native alpha- and beta-spectrin chains and with recombinant
      spectrin fragments encompassing the entire sequences of both chains. We show that
      both alpha-spectrin and beta-spectrin bind PS and that sites of high affinity are
      located within 8 of the 38 triple-helical structural repeats which make up the
      bulk of both chains; these are alpha8, alpha9-10, beta2, beta3, beta4, beta12,
      beta13, and beta14, and PS affinity was also found in the nonhomologous N
      terminal domain of the beta-chain. No other fragments of either chain showed
      appreciable binding. Binding of spectrin and its constituent chains to mixed
      liposomes of PS and phosphatidylcholine (PC) depended on the proportion of PS.
      Binding of spectrin dimers to PS liposomes was inhibited by single repeats
      containing PS binding sites. It is noteworthy that the PS binding sites in beta
      spectrin are grouped in close proximity to the sites of attachment both of
      ankyrin and of 4.1R, the proteins engaged in attachment of spectrin to the
      membrane. We conjecture that direct interaction of spectrin with PS in the
      membrane may modulate its interactions with the proteins and that (considering
      also the known affinity of 4.1R for PS) the formation of PS-rich lipid domains,
      which have been observed in the red cell membrane, may be a result.

PMID- 14717585
TI  - Characterization of the monomer-dimer equilibrium of human cytomegalovirus
      protease by kinetic methods.
AB  - Herpesviruses encode a serine protease that is essential for the maturation of
      infectious virions. This protease has a unique polypeptide backbone fold and
      contains a novel Ser-His-His catalytic triad. It exists in a monomer-dimer
      equilibrium in solution, but only the dimer form of the enzyme is catalytically
      active. The stability of this dimer is affected by the presence of anti
      chaotropic agents. Most of the reported Kd values for this dimer (between 0.6 and
      6 microM) are inconsistent with the fact that the protease is routinely assayed
      at 20-50 nM concentrations, as only monomeric species would be expected with such
      Kd values. We have characterized the monomer-dimer equilibrium of HCMV protease
      using a new method, which observes the exchange between dimers of the wild-type
      enzyme and the active-site Ser132Ala mutant in a titration experiment. The Kd of
      the dimer was determined to be 8 microM and 31 nM in the absence or presence of
      anti-chaotropic agents (10% glycerol and 0.5 M Na2SO4), respectively. Detailed
      kinetic analysis also showed that, in addition to the 260-fold stabilization of
      the dimer, the anti-chaotropic agents produced a 7-fold enhancement in the
      catalytic activity of the dimer.

PMID- 14717586
TI  - Detergent-dependent dissociation of active gamma-secretase reveals an interaction
      between Pen-2 and PS1-NTF and offers a model for subunit organization within the
      complex.
AB  - Gamma-secretase is a member of a new class of proteases with an intramembrane
      catalytic site and cleaves numerous type I membrane proteins, including the
      amyloid beta-protein precursor (APP) and the Notch receptor. Biochemical and
      genetic studies have identified four membrane proteins as components of gamma
      secretase: a heterodimeric form of presenilin (PS), composed of its N- and C
      terminal fragments (PS-NTF and PS-CTF, respectively), a highly glycosylated,
      mature form of nicastrin (NCT), Aph-1, and Pen-2. However, it is unclear how
      these components interact physically with each other and assemble into functional
      complexes. We and others recently found that Aph-1 interacts with a less
      glycosylated, immature form of nicastrin as an intermediate toward full assembly
      of gamma-secretase. Here we show that (1) the detergent dodecyl beta-d-maltoside
      (DDM) mediates the dissociation and inactivation of active gamma-secretase in a
      concentration-dependent manner, (2) DDM-dependent dissociation of the active
      gamma-secretase complex generates two major inactive complexes (Pen-2-PS1-NTF and
      mNCT-Aph-1) and two minor inactive complexes (mNCT-Aph1-PS1-CTF and PS1-NTF-PS1
      CTF), and (3) Pen-2 can also associate with the PS holoprotein in complexes
      devoid of NCT and Aph-1. Taken together, our results demonstrate that Pen-2
      interacts with PS-NTF within active gamma-secretase and offer a model for how the
      components of active gamma-secretase interact physically with each other.

PMID- 14717587
TI  - Inhibition of telomerase activity by preventing proper assemblage.
AB  - Telomerase is a ribonucleoprotein complex that acts as a reverse transcriptase in
      the maintenance of chromosome ends. Because the vast majority of cancer cells
      require telomerase activity, telomerase has become a target for anticancer drug
      discovery. Here, we describe a new approach for targeting telomerase by blocking
      the association between the telomerase catalytic subunit, hTERT, and key elements
      of the human telomerase RNA subunit, hTR. By examining the effects of
      oligonucleotides that hybridize to various regions of hTR, we identified two
      regions of the RNA subunit that are sensitive to molecular interactions leading
      to telomerase inhibition. Oligonucleotides that hybridize to either the P3/P1
      pairing region or to the CR4-CR5 domain of hTR, hTRas009, and hTRas010,
      respectively, inhibit telomerase activity when added to recombinant hTERT and hTR
      prior to assemblage. However, addition of hTRas009 or hTRas010 to preassembled
      telomerase resulted in little or no inhibition. We also examined the ability of
      hTRas009 and hTRas010 to inhibit binding of hTR and hTR fragments to hTERT. We
      found that hTRas009 inhibited approximately 50% of the maximum binding between
      the pseudoknot fragment of hTR (nucleotides 46-209) and hTERT, whereas hTRas010
      inhibited over 90% of the maximum binding between the CR4-CR5 fragment of hTR
      (nucleotides 243-328) and hTERT. In addition, neither oligonucleotide was able to
      appreciably inhibit the binding of full-length hTR to hTERT, although both
      oligonucleotides used in conjunction decreased binding by approximately 50%. We
      propose that the P3/P1 pairing region and CR4-CR5 domain represent viable targets
      to inhibit telomerase by perturbing proper assemblage of the active complex.

PMID- 14717588
TI  - Albumin oxidation to diverse radicals by the peroxidase activity of Cu,Zn
      superoxide dismutase in the presence of bicarbonate or nitrite: diffusible
      radicals produce cysteinyl and solvent-exposed and -unexposed tyrosyl radicals.
AB  - The peroxidase activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) has been
      extensively studied in recent years due to its potential relationship to familial
      amyotrophic lateral sclerosis. The mechanism by which Cu,Zn-SOD/hydrogen
      peroxide/bicarbonate is able to oxidize substrates has been proposed to be
      dependent on an oxidant whose nature, diffusible carbonate radical anion or
      enzyme-bound peroxycarbonate, remains debatable. One possibility to distinguish
      these species is to examine whether protein targets are oxidized to protein
      radicals. Here, we used EPR methodologies to study bovine serum albumin (BSA)
      oxidation by Cu,Zn-SOD/hydrogen peroxide in the absence and presence of
      bicarbonate or nitrite. The results showed that BSA oxidation in the presence of
      bicarbonate or nitrite at pH 7.4 produced mainly solvent-exposed and -unexposed
      BSA-tyrosyl radicals, respectively. Production of the latter was shown to be
      preceded by BSA-cysteinyl radical formation. The results also showed that
      hydrogen peroxide/bicarbonate extensively oxidized BSA-cysteine to the
      corresponding sulfenic acid even in the absence of Cu,Zn-SOD. Thus, our studies
      support the idea that peroxycarbonate acts as a two-electron oxidant and may be
      an important biological mediator. Overall, the results prove the diffusible and
      radical nature of the oxidants produced during the peroxidase activity of Cu,Zn
      SOD in the presence of bicarbonate or nitrite.

PMID- 14717589
TI  - Parallel evolutionary pathways for glutathione transferases: structure and
      mechanism of the mitochondrial class kappa enzyme rGSTK1-1.
AB  - The class kappa glutathione (GSH) transferase is an enzyme that resides in the
      mitochondrial matrix. Its relationship to members of the canonical GSH
      transferase superfamily has remained an enigma. The three-dimensional structure
      of the class kappa enzyme from rat (rGSTK1-1) in complex with GSH has been solved
      by single isomorphous replacement with anomalous scattering at a resolution of
      2.5 A. The structure reveals that the enzyme is more closely related to the
      protein disulfide bond isomerase, dsbA, from Escherichia coli than it is to
      members of the canonical superfamily. The structures of rGSTK1-1 and the
      canonical superfamily members indicate that the proteins folds have diverged from
      a common thioredoxin/glutaredoxin progenitor but did so by different mechanisms.
      The mitochondrial enzyme, therefore, represents a fourth protein superfamily that
      supports GSH transferase activity. The thioredoxin domain functions in a manner
      that is similar to that seen in the canonical enzymes by providing key structural
      elements for the recognition of GSH. The hydroxyl group of S16 is within hydrogen
      bonding distance of the sulfur of bound GSH and is, in part, responsible for the
      ionization of the thiol in the E*GSH complex (pKa = 6.4 +/- 0.1). Preequilibrium
      kinetic experiments indicate that the k(on) for GSH is 1 x 10(5) M(-1) s(-1) and
      k(off) for GS- is approximately 8 s(-1) and relatively slow with respect to
      turnover with 1-chloro-2, 4-dinitrobenzene (CDNB). As a result, the KM(GSH) (11
      mM) is much larger than the apparent Kd(GSH) (90 microM). The active site has a
      relatively open access channel that is flanked by disordered loops that may
      explain the relatively high turnover number (280 s(-1) at pH 7.0) toward CDNB.
      The disordered loops form an extensive contiguous patch on one face of the
      dimeric enzyme, a fact that suggests that the protein surface may interact with a
      membrane or other protein partner.

PMID- 14717590
TI  - Structures of enterococcal glycerol kinase in the absence and presence of
      glycerol: correlation of conformation to substrate binding and a mechanism of
      activation by phosphorylation.
AB  - The first structure of a glycerol kinase from a Gram-positive organism,
      Enterococcus casseliflavus, has been determined to 2.8 A resolution in the
      presence of glycerol and to 2.5 A resolution in the absence of substrate. The
      substrate-induced closure of 7 degrees is significantly smaller than that
      reported for hexokinase, a model for substrate-mediated domain closure that has
      been proposed for glycerol kinase. Despite the 78% level of sequence identity and
      conformational similarity in the catalytic cleft regions of the En. casseliflavus
      and Escherichia coli glycerol kinases, remarkable structural differences have now
      been identified. These differences correlate well with their divergent regulatory
      schemes of activation by phosphorylation in En. casseliflavus and allosteric
      inhibition in E. coli. On the basis of our structural results, we propose a
      mechanism by which the phosphorylation of a histidyl residue located 25 A from
      the active site results in a 10-15-fold increase in the activity of the
      enterococcal glycerol kinase.

PMID- 14717591
TI  - Effect of cofactor binding and loop conformation on side chain methyl dynamics in
      dihydrofolate reductase.
AB  - Dihydrofolate reductase (DHFR) has several flexible active site loops that
      facilitate ligand binding and catalysis. Previous studies of backbone dynamics in
      several complexes of DHFR indicate that the time scale and amplitude of motion
      depend on the conformation of the active site loops. In this study, information
      on dynamics is extended to methyl-containing side chains. To understand the role
      of side chain dynamics in ligand binding and loop conformation, methyl deuterium
      relaxation rates of Escherichia coli DHFR in binary folate and ternary
      folate:NADP+ complexes have been measured, together with chi(1) rotamer
      populations for threonine, isoleucine, and valine residues, determined from
      measurements of 3J(CgammaCO) and 3J(CgammaN) coupling constants. The results
      indicate that, in addition to backbone motional restriction in the adenosine
      binding site, side chain flexibility in the active site and the surrounding
      active site loops is diminished upon binding NADP+. Resonances for several
      methyls in the active site and the surrounding active site loops were severely
      broadened in the folate:NADP+ ternary complex, suggesting the presence of motion
      on the chemical shift time scale. The side chains of Ile14 and Ile94, which pack
      against the nicotinamide and pterin rings of the cofactor and substrate,
      respectively, exhibit rotamer disorder in the ternary folate:NADP+ complex.
      Conformational fluctuations of these side chains may play a role in transition
      state stabilization; the observed line broadening for Ile14 suggests motions on a
      microsecond/millisecond time scale.

PMID- 14717592
TI  - Interdomain communication between weak structural elements within a disease
      related human tRNA.
AB  - The structure of the human mitochondrial (hs mt) tRNALeu(UUR) features several
      domains that are predicted to exhibit limited thermodynamic stability. An
      elevated frequency of disease-related mutations within these domains suggests a
      link between structural instability and the functional effects of pathogenic
      mutations. A series of tRNAs featuring mutations within the D and anticodon stems
      were prepared and investigated using nuclease probing. Structural mapping studies
      indicated that these domains were partially denatured for the wild type (WT) hs
      mt tRNALeu(UUR) and were significantly stabilized by mutations introducing
      additional or stronger base pairs into the stem regions. In addition, trends in
      the aminoacylation activities of the D stem mutants suggested that the loose
      structure is required for function, with mutants displaying the most ordered
      structures exhibiting the lowest levels of aminoacylation activity. A pronounced
      interdependence of the structures of the anticodon and D stems was observed, with
      mutations strengthening the D stem stabilizing the anticodon stem and vice versa.
      The existence of strong interdomain communication was further elucidated with a
      mutant of hs mt tRNALeu(UUR) containing a stabilized D stem and a pathogenic
      mutation that disrupted the anticodon stem. Strengthening the structure of the D
      stem completely restored the function of the disease-related mutant to WT levels,
      indicating that propagated structural weaknesses contribute to the functional
      deactivation of this tRNA by mutations.

PMID- 14717593
TI  - Evaluating the contribution of base stacking during translesion DNA replication.
AB  - Despite the nontemplating nature of the abasic site, dAMP is often preferentially
      inserted opposite the lesion, a phenomenon commonly referred to as the "A-rule".
      We have evaluated the molecular mechanism accounting for this unique behavior
      using a thorough kinetic approach to evaluate polymerization efficiency during
      translesion DNA replication. Using the bacteriophage T4 DNA polymerase, we have
      measured the insertion of a series of modified nucleotides and have demonstrated
      that increasing the size of the nucleobase does not correlate with increased
      insertion efficiency opposite an abasic site. One analogue, 5-nitroindolyl-2'
      deoxyriboside triphosphate, was unique as it was inserted opposite the lesion
      with approximately 1000-fold greater efficiency compared to that for dAMP
      insertion. Pre-steady-state kinetic measurements yield a kpol value of 126 s(-1)
      and a Kd value of 18 microM for the insertion of 5-nitroindolyl-2'-deoxyriboside
      triphosphate opposite the abasic site. These values rival those associated with
      the enzymatic formation of a natural Watson-Crick base pair. These results not
      only reiterate that hydrogen bonding is not necessary for nucleotide insertion
      but also indicate that the base-stacking and/or desolvation capabilities of the
      incoming nucleobase may indeed play the predominant role in generating efficient
      DNA polymerization. A model accounting for the increase in catalytic efficiency
      of this unique nucleobase is provided and invokes pi-pi stacking interactions of
      the aromatic moiety of the incoming nucleobase with aromatic amino acids present
      in the polymerase's active site. Finally, differences in the rate of 5
      nitroindolyl-2'-deoxyriboside triphosphate insertion opposite an abasic site are
      measured between the bacteriophage T4 DNA polymerase and the Klenow fragment.
      These kinetic differences are interpreted with regard to the differences in
      various structural components between the two enzymes and are consistent with the
      proposed model for DNA polymerization.

PMID- 14717594
TI  - Role of histidine-85 in the catalytic mechanism of thymidine phosphorylase as
      assessed by targeted molecular dynamics simulations and quantum mechanical
      calculations.
AB  - The structural changes taking place in the enzyme thymidine phosphorylase (TPase,
      also known as PD-ECGF) that are required to achieve catalytic competence upon
      binding thymidine and phosphate have been simulated by means of targeted
      molecular dynamics (tMD). The hinge regions were characterized by structural
      homology comparisons with pyrimidine nucleoside phosphorylase, whose X-ray
      structure has been solved both in a closed and in an open form. The rearrangement
      of residues around the substrate that was observed during the tMD trajectory
      suggested that His-85 could be playing an important role in the catalytic
      mechanism. A quantum mechanical study of the reaction in the presence of the most
      relevant active site residues was then performed at the semiempirical level. The
      results revealed that His-85 could be involved in the protonation of the
      pyrimidine base at the O2 position to yield the enol tautomer of the base. To
      establish the role of this oxygen atom in the reaction, ground states, transition
      states, and final products were studied using higher level ab initio methods
      starting from both thymidine and 2-thiothymidine as alternative substrates.
      Comparison of both transition states showed that replacing the oxygen at position
      2 of the pyrimidine base by sulfur should accelerate the reaction rate.
      Consistent with this result, 2-thiothymidine was shown to be a better substrate
      for TPase than the natural substrate, thymidine. For simulating the final step of
      the reaction, tMD simulations were used to study domain opening upon product
      formation considering both the enol and keto tautomers of thymine. Product
      release from the enzyme was easiest in the simulation that incorporated the keto
      tautomer of thymine, suggesting that the enol intermediate spontaneously
      tautomerizes back to the more energetically stable keto form. These results
      highlight a previously unreported role for His-85 in the catalytic mechanism of
      TPase and can have important implications for the design of novel TPase
      inhibitors.

PMID- 14717595
TI  - Energetics of domain-domain interactions and entropy driven association of beta
      crystallins.
AB  - Beta-crystallins are major protein constituents of the mammalian lens, where
      their stability and association into higher order complexes are critical for lens
      clarity and refraction. They undergo modification as the lens ages, including
      cleavage of their terminal extensions. The energetics of betaA3- and betaB2
      crystallin association was studied using site-directed mutagenesis and analytical
      ultracentrifugation. Recombinant (r) murine wild type betaA3- and betaB2
      crystallins were modified by removal of either the N-terminal extension of betaA3
      (rbetaA3Ntr) or betaB2 (rbetaB2Ntr), or both the N- and C-terminal extensions of
      betaB2 (rbetaB2NCtr). The proteins were expressed in Sf9 insect cells or
      Escherichia coli and purified by gel-filtration and ion-exchange chromatography.
      All beta-crystallins studied demonstrated fast reversible monomer-dimer
      equilibria over the temperature range studied (5-35 degrees C) with a tendency to
      form tighter dimers at higher temperatures. The N-terminal deletion of rbetaA3
      (rbetaA3Ntr) significantly increases the enthalpy (+10.9 kcal/mol) and entropy
      (+40.7 cal/deg mol) of binding relative to unmodified protein. Removal of both N-
      and C-terminal extensions of rbetaB2 also increases these parameters but to a
      lesser degree. Deletion of the betaB2-crystallin N-terminal extension alone
      (rbetaB2Ntr) gave almost no change relative to rbetaB2. The resultant net
      negative changes in the binding energy suggest that betaAlpha3- and betaB2
      crystallin association is entropically driven. The thermodynamic consequences of
      the loss of betaAlpha3-crystallin terminal extensions by in vivo proteolytic
      processing could increase their tendency to associate and so promote the
      formation of higher order associates in the aging and cataractous lens.

PMID- 14717596
TI  - Three-dimensional structure of the mini-M conotoxin mr3a.
AB  - Conotoxin mr3a from the venom of Conus marmoreus, a novel peptide that induces
      rolling seizures in mice, has the peptide sequence GCCGSFACRFGCVOCCV, where O is
      trans-4-hydroxyproline, and the chain is cross-linked with disulfide bonds
      between Cys-2 and Cys-16, Cys-3 and Cys-12, and Cys-8 and Cys-15. The tertiary
      structure of mr3a was determined by 2D 1H NMR in combination with a standard
      distance-geometry algorithm. The final set of 22 structures for the peptide had a
      mean global backbone RMS deviation of 0.53 +/- 0.22 A based on 51 NOE, 6 hydrogen
      bond, 6 phi dihedral angle, and 3 disulfide bond constraints. Conotoxin mr3a is
      the first example of the new mini-M branch of conopeptides in the M superfamily.
      Members of the maxi-M branch, whose structures are known, include the mu- and psi
      conotoxins, both of which share a common disulfide bond connectivity. Although
      mr3a has the same arrangement of Cys residues as the mu- and psi-conotoxins, its
      disulfide connectivity is different. This gives mr3a a distinctive "triple-turn"
      backbone.

PMID- 14717597
TI  - Orientation of the g-tensor axes of the Rieske subunit in the cytochrome bc1
      complex.
AB  - The orientation of the g-tensors of the Rieske iron-sulfur protein subunit was
      determined in a single crystal of the bovine mitochondrial cytochrome bc1 complex
      with stigmatellin in the Qo quinol binding site. The g-tensor principal axes are
      skewed with respect to the Fe-Fe and S-S atom direction in the 2Fe2S cluster,
      which is allowed by the lack of rigorous symmetry of the cluster. The asymmetric
      unit in the crystal is the active dimer, and the g-tensor axes have slightly
      different orientations relative to the iron-sulfur cluster in the two halves of
      the dimer. The g approximately 1.79 axis makes an average angle of 30 degrees
      with respect to the Fe-Fe direction and the g approximately 2.024 axis an average
      angle of 26 degrees with respect to the S-S direction. This assignment of the g
      tensor axis directions indicates that conformations of the Rieske protein are
      likely the same in the cytochrome bc1 and b6f complexes and that the extent of
      motion of the Rieske head domain during the catalytic cycle has been highly
      conserved during evolution of these distantly related complexes.

PMID- 14717598
TI  - Electron transfer from HiPIP to the photooxidized tetraheme cytochrome subunit of
      Allochromatium vinosum reaction center: new insights from site-directed
      mutagenesis and computational studies.
AB  - The kinetics of electron transfer from reduced high-potential iron-sulfur protein
      (HiPIP) to the photooxidized tetraheme cytochrome c subunit (THC) bound to the
      photosynthetic reaction center (RC) from the purple sulfur bacterium
      Allochromatium vinosum were studied under controlled redox conditions by flash
      absorption spectroscopy. At ambient redox potential Eh = +200 mV, where only the
      high-potential (HP) hemes of the THC are reduced, the electron transfer from
      HiPIP to photooxidized HP heme(s) follows second-order kinetics with rate
      constant k = (4.2 +/- 0.2) 10(5) M(-1) s(-1) at low ionic strength. Upon
      increasing the ionic strength, k increases by a maximum factor of ca. 2 at 640 mM
      KCl. The role of Phe48, which lies on the external surface of HiPIP close to the
      [Fe4S4] cluster and presumably on the electron transfer pathway to cytochrome
      heme(s), was investigated by site-directed mutagenesis. Substitution of Phe48
      with arginine, aspartate, and histidine completely prevents electron donation.
      Conversely, electron transfer is still observed upon substitution of Phe48 with
      tyrosine and tryptophan, although the rate is decreased by more than 1 order of
      magnitude. These results suggest that Phe48 is located on a key protein surface
      patch essential for efficient electron transfer, and that the presence of an
      aromatic hydrophobic residue on the putative electron-transfer pathway plays a
      critical role. This conclusion was supported by protein docking calculations,
      resulting in a structural model for the HiPIP-THC complex, which involves a
      docking site close to the LP heme farthest from the bacteriochlorophyll special
      pair.

PMID- 14717599
TI  - Molecular mechanism of the enterococcal aminoglycoside 6'-N-acetyltransferase':
      role of GNAT-conserved residues in the chemistry of antibiotic inactivation.
AB  - The Gram-positive pathogen Enterococcus faecium is intrinsically resistant to
      aminoglycoside antibiotics due to the presence of a chromosomally encoded
      aminoglycoside 6'-N-acetyltransferase [AAC(6')-Ii]. This enzyme is a member of
      the GCN5-related N-acetyltransferase (GNAT) superfamily and is therefore
      structurally homologous to proteins that catalyze acetyl transfer to diverse acyl
      accepting substrates. This study reports the investigation of several potential
      catalytic residues that are present in the AAC(6')-Ii active site and also
      conserved in many GNAT enzymes. Site-directed mutagenesis of Glu72, His74, Leu76,
      and Tyr147 with characterization of the purified site mutants gave valuable
      information about the roles of these amino acids in acetyl transfer chemistry.
      More specifically, steady-state kinetic analysis of protein activity, solvent
      viscosity effects, pH studies, and antibiotic resistance profiles were all used
      to assess the roles of Glu72 and His74 as potential active site bases, Tyr147 as
      a general acid, and the importance of the amide NH group of Leu76 in transition
      state stabilization. Taken together, our results indicate that Glu72 is not
      involved in general base catalysis, but is instead critical for the proper
      positioning and orientation of aminoglycoside substrates in the active site.
      Similarly, His74 is also not acting as the active site base, with pH studies
      revealing that this residue must be protonated for optimal AAC(6')-Ii activity.
      Mutation of Tyr147 was found not to affect the chemical step of catalysis, and
      our results were not consistent with this residue acting as a general acid. Last,
      the amide NH group of Leu76 is implicated in important interactions with acetyl
      CoA and transition-state stabilization. In summary, the work described here
      provides important information regarding the molecular mechanism of AAC(6')-Ii
      catalysis that allows us to contrast our findings with those of other GNAT
      proteins and to demonstrate that these enzymes use a variety of chemical
      mechanisms to accelerate acyl transfer.

PMID- 14717600
TI  - Phospholamban binds in a compact and ordered conformation to the Ca-ATPase.
AB  - Mutagenesis and cross-linking measurements have identified specific contact
      interactions between the cytosolic and the transmembrane sequences of
      phospholamban (PLB) and the Ca-ATPase, and in conjunction with the high
      resolution structures of PLB and the Ca-ATPase, have been used to construct
      models of the PLB-ATPase complex, which suggest that PLB adopts a more extended
      structure within this complex. To directly test these predictions, we have used
      fluorescence resonance energy transfer to measure the average conformation and
      heterogeneity between chromophores covalently bound to the transmembrane and
      cytosolic domains of PLB reconstituted in proteoliposomes. In the absence of the
      Ca-ATPase, the cytosolic domain of PLB assumes a wide range of structures
      relative to the transmembrane sequence, which can be described using a model
      involving a Gaussian distribution of distances with an average distance (Rav) of
      less than 21 A and a half-width (HW) of 36 A. This conformational heterogeneity
      of PLB is consistent with the 10 structures resolved by NMR for the C41F mutant
      of PLB in organic cosolvents. In contrast, PLB bound to the Ca-ATPase assumes a
      unique and highly ordered conformation, where Rav = 14.0 +/- 0.3 A and HW = 3.7
      +/- 0.6 A. The small spatial separation between the bound chromophores on PLB is
      inconsistent with an extended conformation of bound PLB in current models. Thus,
      to satisfy known interaction sites of PLB and the Ca-ATPase, these findings
      suggest a reorientation of the nucleotide binding domain of the Ca-ATPase toward
      the bilayer surface to bring known PLB binding sites into close juxtaposition
      with residues near the amino-terminus of PLB. Induction of an altered
      conformation of the nucleotide binding domain of the Ca-ATPase by PLB binding is
      suggested to underlie the reduced calcium sensitivity associated with PLB
      inhibition of the pump.

PMID- 14717601
TI  - Interaction of fibronectin type II proteins with membranes: the stallion seminal
      plasma protein SP-1/2.
AB  - Seminal plasma of mammalians contains, among others, proteins that are
      characterized by the fibronectin (Fn) type II module. Our knowledge about the
      structure and the physiological function of seminal Fn type II proteins mainly
      originates from studies on PDC-109, the bovine representative of this protein
      family. The present work focuses on the equine protein SP-1/2 (also named HSP
      1/2) with particular emphasis on its interaction with lipid membranes by
      employing the intrinsic protein fluorescence and a number of spin-labeled and
      fluorescent lipid analogues. The results indicate that the interaction of SP-1/2
      with (lipid) membranes is similar to that of PDC-109 which can be explained by
      homologous amino acid sequences of both proteins. Like PDC-109, SP-1/2 has a
      specificity for phospholipids with the phosphocholine headgroup. Upon binding to
      lipid vesicles, the protein intercalates into the hydrophobic membrane core,
      resulting in a rigidification of the lipid phase and, at higher concentration, in
      a perturbation of membrane structure. However, compared with PDC-109, the impact
      of SP-1/2 on membranes is less intense in that the degree of protein-mediated
      immobilization of lipids was lower. Furthermore, different to PDC-109, SP-1/2 was
      not able to extract lipids from human red blood cells. The data are discussed
      with regard to similarities and species-specific differences of the function of
      seminal Fn type II proteins in the genesis of sperm cells.

PMID- 14717602
TI  - Redox modulation of integrin [correction of integin] alpha IIb beta 3 involves a
      novel allosteric regulation of its thiol isomerase activity.
AB  - The molecular mechanisms involved in regulating the activation-dependent
      conformational switch in integrins are not known although recent evidence
      suggests that integrins are a direct target for redox modulation. We have
      identified an endogenous integrin thiol isomerase activity that may be
      responsible for regulating integrin activation states. The purpose of this study
      was to examine the effects of redox conditions elicited by nitric oxide and
      glutathione on the thiol isomerase activity of the platelet integrin
      alphaIIbbeta3 and also on the activation status of this integrin in intact
      platelets. The universal integrin activator, Mn2+, stimulates the thiol isomerase
      activity in purified alphaIIbbeta3. Kinetic analysis reveals that alphaIIbbeta3
      is an allosteric enzyme which displays positive cooperativity in the presence of
      Mn2+ with an apparent Hill coefficient of 1.9. Also, addition of Mn2+ to
      platelets results solely in activation of the integrin as demonstrated by the
      binding of the antibody PAC-1. The addition of the nitric oxide donors SNP, SIN
      1, and SNOAC in combination with glutathione can directly reverse the activation
      state of the platelet integrin induced by Mn2+. These compounds have no effect on
      platelet secretory responses indicating a direct effect on the integrin. In the
      presence of nitric oxide and glutathione, the enzymatic activity of alphaIIbbeta3
      also displays positive cooperativity (apparent Hill coefficient of 1.9), and a
      significant increase in the saturability of the enzyme was observed. Thus, redox
      agents simultaneously modulate the thiol isomerase activity of purified
      alphaIIbbeta3 and its active conformation in intact platelets, suggesting a
      molecular mechanism for integrin regulation.

PMID- 14717603
TI  - Mechanism-based approach to the successful prevention of cocaine inhibition of
      the neuronal (alpha 3 beta 4) nicotinic acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor (nAChR) belongs to a family of five channel
      forming proteins that regulate communication between the approximately 10(12)
      cells of the nervous system. A minimum mechanism of inhibition of the muscle-type
      nAChR (1) by the noncompetitive inhibitors cocaine and MK-801 [(+)-dizocilpine,
      an anticonvulsant] indicated they bind to a regulatory site, with higher affinity
      for the closed-channel form than for the open-channel form, thus shifting the
      equilibrium toward the closed-channel form and inhibiting receptor function. The
      mechanism predicts that compounds that bind to this regulatory site with equal or
      higher affinity for the open-channel conformation than for the closed-channel
      conformation will prevent receptor inhibition (1). Does a neuronal form of the
      receptor behave similarly? The mechanism of inhibition of the neuronal nAChR by
      cocaine and MK-801 using rapid chemical kinetic techniques was investigated. The
      alpha3beta4 nAChR stably expressed in HEK 293 cells was used in these
      investigations. Whole-cell currents originated from a major and minor nAChR
      isoform. Only the major isoform has been characterized. For the dominant, rapidly
      desensitizing isoform, the carbamoylcholine dissociation constant for the site
      controlling receptor activation, Kd, is 2 mM; the channel-opening equilibrium
      constant, Phi(-1), is 4; and the dominant desensitization rate constant, k34, is
      20 s(-1). Cocaine inhibits the receptor noncompetitively, with an apparent KI of
      84 and 26 microM at high and low carbamoylcholine concentrations, at which
      concentrations the receptor is mainly in the open- or closed-channel form,
      respectively. Similar results were obtained with MK-801. A combinatorially
      synthesized RNA ligand and a cocaine analogue alleviated cocaine inhibition of
      this neuronal receptor.

PMID- 14717604
TI  - Electron transfer in human methionine synthase reductase studied by stopped-flow
      spectrophotometry.
AB  - Human methionine synthase reductase (MSR) is a key enzyme in folate and
      methionine metabolism as it reactivates the catalytically inert cob(II)alamin
      form of methionine synthase (MS). Electron transfer from MSR to the cob(II)alamin
      cofactor coupled with methyl transfer from S-adenosyl methionine returns MS to
      the active methylcob(III)alamin state. MSR contains stoichiometric amounts of FAD
      and FMN, which shuttle NADPH-derived electrons to the MS cob(II)alamin cofactor.
      Herein, we have investigated the pre-steady state kinetic behavior of the
      reductive half-reaction of MSR by anaerobic stopped-flow absorbance and
      fluorescence spectroscopy. Photodiode array and single-wavelength spectroscopy
      performed on both full-length MSR and the isolated FAD domain enabled assignment
      of observed kinetic phases to mechanistic steps in reduction of the flavins.
      Under single turnover conditions, reduction of the isolated FAD domain by NADPH
      occurs in two kinetically resolved steps: a rapid (120 s(-1)) phase,
      characterized by the formation of a charge-transfer complex between oxidized FAD
      and NADPH, is followed by a slower (20 s(-1)) phase involving flavin reduction.
      These two kinetic phases are also observed for reduction of full-length MSR by
      NADPH, and are followed by two slower and additional kinetic phases (0.2 and
      0.016 s(-1)) involving electron transfer between FAD and FMN (thus yielding the
      disemiquinoid form of MSR) and further reduction of MSR by a second molecule of
      NADPH. The observed rate constants associated with flavin reduction are dependent
      hyperbolically on NADPH and [4(R)-2H]NADPH concentration, and the observed
      primary kinetic isotope effect on this step is 2.2 and 1.7 for the isolated FAD
      domain and full-length MSR, respectively. Both full-length MSR and the separated
      FAD domain that have been reduced with dithionite catalyze the reduction of
      NADP+. The observed rate constant of reverse hydride transfer increases
      hyperbolically with NADP+ concentration with the FAD domain. The stopped-flow
      kinetic data, in conjunction with the reported redox potentials of the flavin
      cofactors for MSR [Wolthers, K. R., Basran, J., Munro, A. W., and Scrutton, N. S.
      (2003) Biochemistry, 42, 3911-3920], are used to define the mechanism of electron
      transfer for the reductive half-reaction of MSR. Comparisons are made with
      similar stopped-flow kinetic studies of the structurally related enzymes
      cytochrome P450 reductase and nitric oxide synthase.

PMID- 14717605
TI  - The functional significance of the monomeric and trimeric states of the
      photosystem II light harvesting complexes.
AB  - The main light harvesting complex of photosystem II in plants, LHCII, exists in a
      trimeric state. To understand the biological significance of trimerization, a
      comparison has been made been LHCII trimers and LHCII monomers prepared by
      treatment with phospholipase. The treatment used caused no loss of chlorophyll,
      but there was a difference in carotenoid composition, together with the
      previously observed alterations in absorption spectrum. It was found that, when
      compared to monomers, LHCII trimers showed increased thermal stability and a
      reduced structural flexibility as determined by the decreased rate and amplitude
      of fluorescence quenching in low-detergent concentration. It is suggested that
      LHCII should be considered as having two interacting domains: the lutein 1
      domain, the site of fluorescence quenching [Wentworth et al. (2003) J. Biol.
      Chem. 278, 21845-21850], and the lutein 2 domain. The lutein 2 domain faces the
      interior of the trimer, the differences in absorption spectrum and carotenoid
      binding in trimers compared to monomers indicating that the trimeric state
      modulates the conformation of this domain. It is suggested that the lutein 2
      domain controls the conformation of the lutein 1 domain, thereby providing
      allosteric control of fluorescence quenching in LHCII. Thus, the pigment
      configuration and protein conformation in trimers is adapted for efficient light
      harvesting and enhanced protein stability. Furthermore, trimers exhibit the
      optimum level of control of energy dissipation by modulating the development of
      the quenched state of the complex.

PMID- 14717606
TI  - Mechanism of spinach chloroplast ferredoxin-dependent nitrite reductase:
      spectroscopic evidence for intermediate states.
AB  - Nitrite reductases found in plants, algae, and cyanobacteria catalyze the six
      electron reduction of nitrite to ammonia with reduced ferredoxin serving as the
      electron donor. They contain one siroheme and one [4Fe-4S] cluster, acting as
      separate one-electron carriers. Nitrite is thought to bind to the siroheme and to
      remain bound until its complete reduction to ammonia. In the present work the
      enzyme catalytic cycle, with ferredoxin reduced by photosystem 1 as an electron
      donor, has been studied by EPR and laser flash absorption spectroscopy. Substrate
      depletion during enzyme turnover, driven by a series of laser flashes, has been
      demonstrated. A complex of ferrous siroheme with NO, formed by two-electron
      reduction of the enzyme complex with nitrite, has been shown to be an
      intermediate in the enzyme catalytic cycle. The same complex can be formed by
      incubation of free oxidized nitrite reductase with an excess of nitrite and
      ascorbate. Hydroxylamine, another putative intermediate in the reduction of
      nitrite catalyzed by nitrite reductase, was found to react with oxidized nitrite
      reductase to produce the same ferrous siroheme-NO complex, with a characteristic
      formation time of about 13 min. The rate-limiting step for this reaction is
      probably hydroxylamine binding to the enzyme, with the conversion of
      hydroxylamine to NO at the enzyme active site likely being much faster.

PMID- 14717607
TI  - Role of a conserved membrane-embedded acidic residue in the multidrug transporter
      MdfA.
AB  - According to the current topology model of the Escherichia coli multidrug
      transporter MdfA, it contains a membrane-embedded negatively charged residue,
      Glu26, which was shown to play an important role in substrate recognition. To
      further elucidate the role of this substrate recognition determinant, various
      Glu26 replacements were characterized. Surprisingly, studies with neutral MdfA
      substrates showed that, unlike many enzymatic systems where the size and chemical
      properties of binding site residues are relatively defined, MdfA tolerates a
      variety of changes at position 26, including size, hydrophobicity, and charge.
      Moreover, although efficient transport of positively charged substrates requires
      a negative charge at position 26 (Glu or Asp), neutralization of this charge does
      not always abrogate the interaction of MdfA with cationic drugs, thus
      demonstrating that the negative charge does not play an essential role in the
      multidrug transport mechanism. Collectively, these results suggest a link between
      the broad substrate specificity profile of multidrug transporters and the
      structural and chemical promiscuity at their substrate recognition pockets.

PMID- 14717608
TI  - Uptake of botulinum neurotoxin into cultured neurons.
AB  - Botulinum neurotoxins (BoNTs) act within the synaptic terminal to block
      neurotransmitter release. The toxin enters the neuron by binding to neuronal
      membrane receptor(s), being taken up into an endosome-like compartment, and
      penetrating the endosome membrane via a pH-dependent translocation process. Once
      within the synaptic cytoplasm, BoNT serotypes A and E cleave separate sites on
      the C-terminus of the neuronal protein SNAP-25, one of the SNARE proteins
      required for synaptic vesicle fusion. In this study, we measured the effect of
      brief toxin exposure on SNAP-25 proteolysis in neuronal cell cultures as an
      indicator of toxin translocation. The results indicate that (1) uptake of both
      BoNT-A and -E is enhanced with synaptic activity induced by K+ depolarization in
      the presence of Ca2+ and (2) translocation of BoNT-A from the acidic endosomal
      compartment is slow relative to that of BoNT-E. Polyclonal antisera against each
      toxin protect cells when applied with the toxin during stimulation but has no
      effect when added immediately after toxin exposure, indicating that toxin
      endocytosis occurs with synaptic activity. Both serotypes cleave SNAP-25 at
      concentrations between 50 pM and 4 nM. IC50 values for SNAP-25 cleavage are
      approximately 0.5 nM for both serotypes. Inhibition of the pH-dependent
      translocation process by pretreating cultures with concanamycin A (Con A)
      prevents cleavage of SNAP-25 with IC50 values of approximately 25 nM. Addition of
      Con A at times up to 15 min after toxin exposure abrogated BoNT-A action;
      however, addition of Con A after 40 min was no longer protective. In contrast,
      Con A inhibited, but did not prevent, translocation of BoNT-E even when added
      immediately after toxin exposure, indicating that pH-dependent translocation of
      BoNT-E is rapid relative to that of BoNT-A. This study demonstrates that uptake
      of both BoNT-A and -E is enhanced with synaptic activity and that translocation
      of the toxin catalytic moiety into the cytosol occurs at different rates for
      these two serotypes.

PMID- 14717609
TI  - Functional characterization of a maize ribosomal S6 protein kinase (ZmS6K), a
      plant ortholog of metazoan p70(S6K).
AB  - Ribosomal protein S6 (S6rp) is phosphorylated by the p70S6K enzyme in mammals,
      under mitogen/IGF regulation. This event has been correlated with an increase in
      5'TOP mRNA translation. In this research, a maize S6 kinase (ZmS6K) was isolated
      from maize (Zea mays L.) embryonic axes by human p70S6K antibody
      immunoprecipitation. This enzyme, a 62 kDa peptide, proved to be specific for
      S6rp phosphorylation, as revealed by in vivo and in vitro kinase activity using
      either the 40S ribosomal subunit or the RSK synthetic peptide as the substrates.
      ZmS6K activation was achieved by phosphorylation on serine/threonine residues.
      Specific phospho-Threo recognition by the p70S6K antibody directed to target
      phospho-Threo residue 389 correlated with ZmS6K activation. The ZmS6K protein
      content remained almost steady during maize seed germination, whereas the ZmS6K
      activity increased during this process, consistent with Zm6SK phosphorylation.
      Addition of insulin to germinating maize axes proved to increase ZmS6K activity
      and the extent of S6rp phosphorylation. These events were blocked by rapamycin,
      an inhibitor of the insulin signal transduction pathway in mammals, at the TOR
      (target of rapamycin) enzyme level. We conclude that ZmS6K is a kinase,
      structurally and functionally ortholog of the mammalian p70S6K, responsible for
      in vivo S6rp phosphorylation in maize. Its activation is induced by insulin in a
      TOR-dependent manner by phosphorylation on conserved serine/threonine residues.

PMID- 14717610
TI  - Endogenous 5-methylcytosine protects neighboring guanines from N7 and O6
      methylation and O6-pyridyloxobutylation by the tobacco carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone.
AB  - All CG dinucleotides along exons 5-8 of the p53 tumor suppressor gene contain
      endogenous 5-methylcytosine (MeC). These same sites (e.g., codons 157, 158, 245,
      248, and 273) are mutational hot spots in smoking-induced lung cancer. Several
      groups used the UvrABC endonuclease incision assay to demonstrate that methylated
      CG dinucleotides of the p53 gene are the preferred binding sites for the diol
      epoxides of bay region polycyclic aromatic hydrocarbons (PAH). In contrast,
      effects of endogenous cytosine methylation on the distribution of DNA lesions
      induced by tobacco-specific nitrosamines, e.g., 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), have not been elucidated. In the work presented here,
      a stable isotope labeling HPLC-ESI-MS/MS approach was employed to analyze the
      reactivity of the N7 and O6 positions of guanines within hemimethylated and fully
      methylated CG dinucleotides toward NNK-derived methylating and
      pyridyloxobutylating species. 15N3-labeled guanine bases were placed within
      synthetic DNA sequences representing endogenously methylated p53 codons 154, 157,
      and 248, followed by treatment with acetylated precursors to NNK diazohydroxides.
      HPLC-ESI-MS/MS analysis was used to determine the relative yields of N7- and O6
      guanine adducts at the 15N3-labeled position. In all cases, the presence of MeC
      inhibited the formation of N7-methylguanine, O6-methylguanine, and O6
      pyridyloxobutylguanine at a neighboring G, with the greatest decrease observed in
      fully methylated dinucleotides and at guanines preceded by MeC. Furthermore, the
      O6-Me-dG/N7-Me-G molar ratios were decreased in the presence of the 5'
      neighboring MeC, suggesting that the observed decline in O6-alkylguanine adduct
      yields is, at least partially, a result of an altered reactivity pattern in
      methylated CG dinucleotides. These results indicate that, unlike N2-guanine
      adducts of PAH diol epoxides, NNK-induced N7- and O6-alkylguanine adducts are not
      preferentially formed at the endogenously methylated CG sites within the p53
      tumor suppressor gene.

PMID- 14717611
TI  - Estimation of helix-helix association free energy from partial unfolding of
      bacterioopsin.
AB  - To obtain thermodynamic information about interactions between transmembrane
      helices in integral membrane proteins, partial unfolding of bacterioopsin in
      ethanol/water mixtures was studied by Forster-type resonance energy transfer
      (FRET) from tryptophan to a dansyl group on Lys 41. Tryptophan to dansyl FRET was
      detected by measuring sensitized emission at 490-500 nm from 285 nm excitation.
      FRET was observed in dansylbacterioopsin in apomembranes and in detergent
      micelles but not in 90% ethanol/water or in the chymotrypsin fragment C2
      (residues 1-71). The main fluorescence donors are Trp 86 and Trp 182. Increase of
      FRET from C2 with added chymotrypsin fragment C1 (residues 72-248) provides an
      estimate of the C1-C2 association constant as 7.7 x 10(6) M(-1). With increasing
      ethanol concentration, the FRET signal from dansylbacterioopsin in detergent
      micelles disappeared with a sharp transition above 60% ethanol. No transition
      occurred in Trp fluorescence from bacterioopsin lacking the dansyl acceptor, nor
      did dansyl model compounds undergo a similar transition. Light scattering
      measurements show that the detergent micelles dissipate below 50% ethanol. Thus
      the observed transition is likely to be a partial unfolding of bacterioopsin.
      Assuming a two-state unfolding model, the free energy of unfolding was obtained
      by extrapolation as 9.0 kcal/mol. The slope of the transition (m-value) was -0.8
      kcal mol(-1) M(-1). The unfolding process probably involves dissociation of
      several helices. The rate of association was measured by stopped-flow
      fluorometry. Two first-order kinetic processes were observed, having
      approximately equal weights, with rate constants of 2.32 s (-1) and 0.185 s(-1).

PMID- 14717612
TI  - Copper mediates dityrosine cross-linking of Alzheimer's amyloid-beta.
AB  - We have previously reported that amyloid Abeta, the major component of senile
      plaques in Alzheimer's disease (AD), binds Cu with high affinity via histidine
      and tyrosine residues [Atwood, C. S., et al. (1998) J. Biol. Chem. 273, 12817
      12826; Atwood, C. S., et al. (2000) J. Neurochem. 75, 1219-1233] and produces
      H(2)O(2) by catalyzing the reduction of Cu(II) or Fe(III) [Huang, X., et al.
      (1999) Biochemistry 38, 7609-7616; Huang, X., et al. (1999) J. Biol. Chem. 274,
      37111-37116]. Incubation with Cu induces the SDS-resistant oligomerization of
      Abeta [Atwood, C. S., et al. (2000) J. Neurochem. 75, 1219-1233], a feature
      characteristic of neurotoxic soluble Abeta extracted from the AD brain. Since
      residues coordinating Cu are most vulnerable to oxidation, we investigated
      whether modifications of these residues were responsible for Abeta cross-linking.
      SDS-resistant oligomerization of Abeta caused by incubation with Cu was found to
      induce a fluorescence signal characteristic of tyrosine cross-linking. Using ESI
      MS and a dityrosine specific antibody, we confirmed that Cu(II) (at
      concentrations lower than that associated with amyloid plaques) induces the
      generation of dityrosine-cross-linked, SDS-resistant oligomers of human, but not
      rat, Abeta peptides. The addition of H2O2 strongly promoted Cu-induced dityrosine
      cross-linking of Abeta1-28, Abeta1-40, and Abeta1-42, suggesting that the
      oxidative coupling is initiated by interaction of H2O2 with a Cu(II) tyrosinate.
      The dityrosine modification is significant since it is highly resistant to
      proteolysis and is known to play a role in increasing structural strength. Given
      the elevated concentration of Cu in senile plaques, our results suggest that Cu
      interactions with Abeta could be responsible for causing the covalent cross
      linking of Abeta in these structures.

PMID- 14717613
TI  - Sterol methyltransferase: functional analysis of highly conserved residues by
      site-directed mutagenesis.
AB  - Sterol methyltransferase (SMT), the enzyme from Saccharomyces cerevisiae that
      catalyzes the conversion of sterol acceptor in the presence of AdoMet to C-24
      methylated sterol and AdoHcy, was analyzed for amino acid residues that
      contribute to C-methylation activity. Site-directed mutagenesis of nine aspartate
      or glutamate residues and four histidine residues to leucine (amino acids highly
      conserved in 16 different species) and expression of the resulting mutant
      proteins in Escherichia coli revealed that residues at H90, Asp125, Asp152,
      Glu195, and Asp276 are essential for catalytic activity. Each of the
      catalytically impaired mutants bound sterol, AdoMet, and 25-azalanosterol, a high
      energy intermediate analogue inhibitor of C-methylation activity. Changes in
      equilibrium binding and kinetic properties of the mutant enzymes indicated that
      residues required for catalytic activity are also involved in inhibitor binding.
      Analysis of the pH dependence of log kcat/Km for the wild-type SMT indicated a pH
      optimum for activity between 6 and 9. These results and data showing that only
      the mutant H90L binds sterol, AdoMet, and inhibitor to similar levels as the wild
      type enzyme suggest that H90 may act as an acceptor in the coupled methylation
      deprotonation reaction. Circular dichroism spectra and chromatographic
      information of the wild-type and mutant enzymes confirmed retention of the
      overall conformation of the enzyme during the various experiments. Taken
      together, our studies suggest that the SMT active center is composed of a set of
      acidic amino acids at positions 125, 152, 195, and 276, which contribute to
      initial binding of sterol and AdoMet and that the H90 residue functions
      subsequently in the reaction progress to promote product formation.

PMID- 14717614
TI  - Disentangling the web of allosteric communication in a homotetramer: heterotropic
      inhibition of phosphofructokinase from Bacillus stearothermophilus.
AB  - A strategy for isolating each of the four potentially unique heterotropic
      pairwise allosteric interactions that exist in the homotetramer
      phosphofructokinase from Bacillus stearothermophilus is described. The strategy
      involves the construction of hybrid tetramers containing one wild-type subunit
      and three mutant subunits that have been modified to block binding of both the
      substrate, fructose 6-phosphate (Fru-6-P), and the allosteric inhibitor,
      phospho(enol)pyruvate (PEP). Each type of binding site occurs at a subunit
      interface, and mutations on either side of the interface have been identified
      that will greatly diminish binding at the respective site. Consequently, four
      different types of mutant subunits have been created, each containing a different
      active site and allosteric site modification. The corresponding 1:3 hybrids
      isolate a different pair of unmodified substrate and allosteric sites with a
      unique structural disposition located 22, 30, 32, and 45 A apart, respectively.
      The allosteric inhibition exhibited by the unmodified sites in each of these four
      hybrids has been quantitatively evaluated in terms of a coupling free energy.
      Each of the coupling free energies is unique in magnitude, and their relative
      magnitudes vary with pH. Importantly, the sum of these coupling free energies at
      each pH is equal to the total heterotropic coupling free energy associated with
      the tetrameric enzyme. The latter quantity was assessed from the overall
      inhibition of a control hybrid that removed the homotropic interactions in PEP
      binding. The results do not agree with either the concerted or sequential models
      that are often invoked to explain allosteric behavior in oligomeric enzymes.

PMID- 14717615
TI  - Myelopathy in Sjogren's syndrome: role of nonsteroidal immunosuppressants.
AB  - The incidence, aetiology and optimal treatment of CNS Sjogren's syndrome,
      including myelopathy associated with Sjogren's syndrome, are unknown at the
      present time. CNS Sjogren's syndrome is thought to be the result of an autoimmune
      vasculitis, but other mechanisms may be important. Spinal cord involvement in CNS
      Sjogren's syndrome may present as acute transverse myelitis, progressive
      myelitis, Brown-Sequard syndrome, neurogenic bladder or lower motor neurone
      disease. Optic nerve pathology frequently accompanies spinal cord involvement.
      Acute transverse myelitis has a high mortality and appears to be the most
      frequent form of spinal cord involvement in CNS Sjogren's syndrome, occurring in
      about 1% of all patients with Sjogren's syndrome. The patient's symptomatology
      and clinical course dictate current treatment of myelopathy. First-line treatment
      appears to be corticosteroid therapy. However, when the patient's condition fails
      to improve or deteriorates a nonsteroidal immunosuppressant agent should be
      considered. Agents used to treat myelopathy include cyclophosphamide,
      chlorambucil, azathioprine, ciclosporin (cyclosporin) and methotrexate in
      conjunction with corticosteroids. Most data exist as anecdotal reports. The agent
      of first choice, based on adverse effect profile and efficacy, appears to be
      cyclophosphamide given intravenously in pulse doses. Other nonsteroidal
      immunosuppressant agents should be considered, especially when lack of efficacy
      of, or intolerance to, cyclophosphamide exists in the patient's history.
      Glandular and other extraglandular symptoms may benefit concomitantly from the
      immunosuppressant treatment. In addition, when acute relief of symptomatology is
      needed, the patient may benefit from a trial of plasmapheresis or intravenous
      immunoglobulin. Infliximab (anti-tumour necrosis factor-alpha antibodies) has not
      been used as a treatment modality for myelopathy, but has shown some usefulness
      in the treatment of extraglandular symptoms, as well as peripheral nervous system
      manifestations of Sjogren's syndrome. This agent might be considered when all
      other treatment modalities have failed given the presumed importance of tumour
      necrosis factor in the pathogenesis of Sjogren's syndrome.

PMID- 14717616
TI  - Management of osteoporosis in adults with cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common genetic disease that causes respiratory
      failure within the Caucasian population. The life span of patients with CF has
      gradually increased from a median of 2 years of age to >30 years. Concurrent with
      this increased lifespan, a variety of other nutritional, endocrine and bone
      issues have been recognised. Decreased absorption of fat-soluble vitamins (D and
      K in particular) because of pancreatic insufficiency, altered sex hormone
      production, chronic inflammation, a lack of physical activity, glucocorticoid
      treatment and an intrinsic hyper-resorptive bone physiology are some of the
      factors that contribute to the prominence of bone disease within the CF
      population. In some series, three-quarters of adult patients with CF have
      osteopenia or osteoporosis. Lung transplantation is one viable treatment for
      patients with end-stage CF, which requires a lifetime of antirejection
      medication. Immunosuppressant therapies have a detrimental effect on bone mineral
      density (BMD). To combat the multifactorial nature of CF-related bone disease,
      advances in nutritional and vitamin supplementation, and anti-resorptive and
      anabolic therapies have evolved. Chronic vitamin D depletion contributes to bone
      disease in the CF population. The isoform of vitamin D that is the best and
      safest supplement, with the lowest cost, has yet to be identified. However, it is
      clear that many patients with CF who receive the standard of care (i.e. two daily
      combination vitamin A, D, E and K tablets [ADEKs]) may still be vitamin D
      deficient. More aggressive supplementation needs to be individualised, with close
      monitoring of serum 25-hydroxyvitamin D levels. Similarly, routine calcium
      supplementation may be important, and evidence is accumulating that vitamin K
      also plays an important role in maximising and maintaining BMD. Early recognition
      and treatment of delayed puberty in adolescents and hypogonadism in adults with
      hormone replacement therapy is recommended to maintain BMD in patients with CF.
      Bisphosphonates, including pamidronic acid, etidronic acid and alendronic acid,
      reduce bone resorption by inhibiting the recruitment and function of osteoclasts.
      Pamidronic acid is beneficial in improving BMD in CF patients before and after
      transplantation. Bisphosphonate therapy and minimisation of glucocorticoid dosage
      have been shown to be efficacious in glucocorticoid-induced osteoporosis.
      Teriparatide is the first US FDA-approved anabolic growth agent for bone, and has
      been shown to increase BMD and decrease fracture incidence in postmenopausal
      women. Teriparatide may offer a new avenue for treating bone disease in CF since
      many patients may have poor bone formation as well as accelerated bone breakdown.
      Numerous clinical trials are underway to optimise treatment of CF osteoporosis.

PMID- 14717617
TI  - Restless legs syndrome: an update on treatment options.
AB  - Restless legs syndrome (RLS) was first described in 1672 but it is only recently
      that this disorder has attracted attention in defining its phenotype, and
      identifying its aetiology, pathogenesis and pharmacological treatment. RLS can be
      divided into primary (idiopathic) and secondary forms. RLS is common, affecting 5
      15% of the total population and manifesting at any age from childhood to late
      adulthood. Prevalence tends to increase with patient age and there may be
      geographic variation. There is a clear genetic contribution to primary RLS and
      evidence for dopaminergic dysfunction. Although not all patients with RLS require
      medication, there can be a substantial reduction in the patient's quality of life
      related to pain, poor sleep and excessive daytime sleepiness. A variety of
      medications are now available for the symptomatic treatment of RLS. Dopaminergic
      therapy is currently the treatment of choice, usually initiated with a long
      acting dopamine agonist, thereby avoiding some of the complications associated
      with levodopa. Anticonvulsants may be used as second-line treatment. Levodopa
      should be reserved for those patients who fail to respond to alternative
      medications because of the high risk of inducing augmentation. Hypnosedatives
      also have a role in RLS management. Patients with intractable RLS may require
      combination treatment. Several systemic disorders can cause RLS, and these should
      be identified and treated appropriately.

PMID- 14717619
TI  - Atomoxetine: a review of its use in adults with attention deficit hyperactivity
      disorder.
AB  - Atomoxetine (Strattera) is a selective norepinephrine reuptake inhibitor and
      nonstimulant that has shown greater efficacy than placebo in attention deficit
      hyperactivity disorder (ADHD) in adults. In two large, well controlled, 10-week
      trials in adults with ADHD, improvements in ADHD symptoms, as assessed by
      investigator- and patient-rated scores, were greater with oral atomoxetine (60,
      90 or 120 mg/day) than with placebo. Mean reductions in the total ADHD symptom
      score on the investigator-rated Conners' Adult ADHD Rating Scale (CAARS) in
      atomoxetine versus placebo recipients were 28.3% versus 18.1% and 30.1% versus
      19.6%, respectively. Mean reductions in the scores on the Clinician Global
      Impression of Severity Scale, patient-rated CAARS and Wender-Reimherr Adult
      Attention Deficit Disorder Scale were also significantly greater with atomoxetine
      than with placebo. Continued efficacy was demonstrated in a noncomparative, 34
      week extension phase. Atomoxetine was generally well tolerated in clinical
      trials; withdrawal rates due to adverse events in atomoxetine-treated versus
      placebo-treated patients participating in the two major trials were 7.8% versus
      4.3% and 9.3% versus 2.4% (p<0.05 for the latter trial). Adverse events reported
      significantly more frequently with atomoxetine than placebo included dry mouth,
      insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria,
      sexual problems and palpitations. Modest increases in heart rate and blood
      pressure were well tolerated and gradually decreased on cessation of treatment.
      Atomoxetine was not associated with QT interval prolongation. Atomoxetine can be
      administered once or twice daily. Its subjective-effects profile is different to
      that of methylphenidate and atomoxetine is not associated with abuse or
      diversion; it is therefore not a controlled substance in the US. This also means
      repeat prescriptions during long-term treatment can be more conveniently
      processed. CONCLUSION: Atomoxetine is an effective and generally well tolerated
      treatment for adults with ADHD. It is a nonstimulant and is the first ADHD
      treatment to be approved specifically for adult use based on its efficacy in well
      controlled adult trials. It can be administered as a single daily dose or split
      into two evenly divided doses. It carries negligible risk of abuse or diversion
      and is not a controlled substance. Atomoxetine is a valuable new treatment option
      for adults with ADHD and is particularly useful in patients who are at risk for
      substance abuse or who do not wish to take a controlled substance.

PMID- 14717620
TI  - Benefits and risks of pharmacological agents used for the treatment of
      menorrhagia.
AB  - Menorrhagia affects the lives of many women. The assessment of menstrual flow is
      highly subjective and gauging the severity of the condition by objective
      assessment of menstrual blood loss is impractical. In treating menorrhagia, the
      primary aim should be to improve quality of life. Women are willing to undergo
      quite invasive treatment in order to achieve this. Drug therapy is the initial
      treatment of choice and the only option for those who wish to preserve their
      reproductive function. Despite the availability of a number of drugs, there is a
      general lack of an evidence-based approach, marked variation in practice and
      continuing uncertainty regarding the most appropriate therapy. Adverse effects
      and problems with compliance also undermine the success of medical treatment.
      This article reviews the available literature to compare the efficacy and
      tolerability of different medical treatments for menorrhagia. Tranexamic acid and
      mefenamic acid are among the most effective first-line drugs used to treat
      menorrhagia. Despite being used extensively in the past, oral luteal phase
      norethisterone is probably one of the least effective agents. Women requiring
      contraception have a choice of the combined oral contraceptive pill,
      levonorgestrel-releasing intrauterine system (LNG-IUS) or long-acting
      progestogens. Danazol, gestrinone and gonadotropin-releasing hormone analogues
      are all effective in terms of reducing menstrual blood loss but adverse effects
      and costs limit their long-term use. They have a role as second-line drugs for a
      short period of time in women awaiting surgery. While current evidence suggests
      that the LNG-IUS is an effective treatment, further evaluation, including long
      term follow up, is awaited. Meanwhile, the quest continues for the ideal form of
      medical treatment for menorrhagia--one that is effective, affordable and
      acceptable.

PMID- 14717621
TI  - A benefit-risk assessment of basiliximab in renal transplantation.
AB  - Interleukin-2 (IL-2) and its receptor (IL-2R) play a central role in T lymphocyte
      activation and immune response after transplantation. Research on the biology of
      IL-2R allowed the identification of key signal transduction pathways involved in
      the generation of proliferative and antiapoptotic signals in T cells. The alpha
      chain of the IL-2R is a specific peptide against which monoclonal antibodies have
      been raised, with the aim of blunting the immune response by means of inhibiting
      proliferation and inducing apoptosis in primed lymphocytes. Indeed, basiliximab,
      one of such antibodies, has proved to be effective in reducing the episodes of
      acute rejection after kidney and pancreas transplantation. The use of basiliximab
      was associated with a significant reduction in the incidence of any treated
      rejection episodes after kidney transplantation in the two major randomised
      studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European study; placebo
      54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and equine
      antithymocyte globulin (ATG) administration resulted in a similar rate of biopsy
      proven acute rejection at 6 months (19% for both) and at 12 months (19% and 20%,
      respectively). The use of basiliximab appears not to be associated with an
      increased incidence of adverse events as compared with placebo in
      immunosuppressive regimens, including calcineurin inhibitors, mycophenolate
      mofetil or azathioprine and corticosteroids, and its safety profile is superior
      to ATG. Moreover, a similar occurrence of infections is noted in selected studies
      (65.5% after basiliximab vs 65.7% of controls), including cytomegalovirus
      infection (17.3% vs 14.5%), and cytokine-release syndrome is not observed.
      Finally, economic analysis demonstrated lower costs of overall treatment in
      patients treated with basiliximab. Therefore, the use of basiliximab entails a
      very low risk, allows safe reduction of corticosteroid dosage and reduces the
      short- and mid-term rejection rates. However, the improvement in the long-term
      survival of kidney grafts in patients treated according to modern
      immunosuppressive protocols is still to be demonstrated. These conclusions are
      based on a systematic review of the scientific literature, indexed on Medline
      database, concerning the mechanism of action, therapeutic activity, safety and
      pharmacoeconomic evaluation of basiliximab in renal transplantation.

PMID- 14717624
TI  - Therapeutic drug monitoring as a tool to identify medication errors.

PMID- 14717623
TI  - Changes in fatalities due to overdose of anxiolytic and sedative drugs in the UK
      (1983-1999).
AB  - OBJECTIVE: To establish the frequency with which anxiolytic and sedative drugs
      result in fatal poisonings and to examine longitudinal changes in poisoning
      deaths. METHOD: The number of fatal poisonings between 1983 and 1999 in England,
      Scotland and Wales due to a single anxiolytic or sedative drug was obtained from
      the Department of Health in the UK. This was divided by the number of
      prescriptions for these drugs in England and Scotland to derive a fatal toxicity
      index (FTI) of deaths per million prescriptions. RESULTS: Chloral hydrate,
      clomethiazole, barbiturates, and related sedatives had much higher FTIs than
      benzodiazepines, buspirone, zolpidem and zopiclone. There has been a substantial
      reduction in the annual number of deaths from sedative drug poisoning between
      1983 and 1999. This has been due to a sustained reduction in prescriptions for
      high toxicity drugs and more recently a major reduction in temazepam deaths that
      coincided with the withdrawal of gelatin capsule formulations. CONCLUSION: Deaths
      would be expected to be further reduced if there were reduced prescriptions of
      high toxicity drugs--and the continuing need for short-acting barbiturates,
      clomethiazole and chloral hydrate should be questioned.

PMID- 14717625
TI  - The relationship between expertise and evaluative extremity: the moderating role
      of experts' task characteristics.
AB  - Past research has yielded contradictory results with regard to the relationship
      between expertise and evaluative extremity. The authors suggest that this
      apparent contradiction is due to the task characteristics of the expert activity.
      The primary task of certain experts is to formulate overall (configural)
      judgments and to generate clear, unambiguous answers. These experts tend to give
      relatively extreme evaluations. Other experts generally communicate the
      implications of the different choice alternatives and explain featural aspects of
      the stimuli. These experts are characterized by relatively moderate evaluations.
      The research reported in this article shows that experts whose expert activity
      involves configural judgments tend to make more extreme evaluations than experts
      who generally provide others with featural explanations. It also demonstrates
      that experts' task characteristics affect the way they store stimulus-relevant
      attributes in memory.

PMID- 14717626
TI  - "It's the end of the world as we know it": threat and the spatial-symbolic self.
AB  - According to amoebic self theory, the boundary defining the self encompasses 3
      levels of self-representation--bodily, social, and spatial-symbolic. Study 1
      related a newly developed measure of individual differences in sensitivity to
      boundary threat across these 3 domains to values and disgust sensitivity. Four
      subsequent studies focused on spatial-symbolic threat sensitivity and related it
      to right-wing authoritarianism, aversive reactions to unfamiliar out-groups, and
      revulsion to vermin. A final experiment illustrates how a salient spatial
      symbolic threat (dust mites) can elicit reactions toward out-groups that closely
      parallel mortality salience effects observed in research inspired by terror
      management theory, even though dust mites do not elicit mortality concerns. The
      importance of preserving the familiar in order to preserve the self is discussed.

PMID- 14717627
TI  - Discrete emotions and persuasion: the role of emotion-induced expectancies.
AB  - The authors argue that specific emotions can alter the persuasive impact of
      messages as a function of the emotional framing of persuasive appeals. Because
      specific emotions inflate expectancies for events possessing matching emotional
      overtones (D. DeSteno, R. E. Petty, D. T. Wegener, & D. D. Rucker, 2000), the
      authors predicted that attempts at persuasion would be more successful when
      messages were framed with emotional overtones matching the emotional state of the
      receiver and that these changes would be mediated by emotion-induced biases
      involving expectancies attached to arguments contained in the messages. Two
      studies manipulating discrete negative emotional states and message frames (i.e.,
      sadness and anger) confirmed these predictions. The functioning of this emotion
      matching bias in parallel with emotion-induced processing differences and the
      limitations of a valence-based approach to the study of attitude change are also
      considered.

PMID- 14717618
TI  - Efflux-mediated drug resistance in bacteria.
AB  - Drug resistance in bacteria, and especially resistance to multiple
      antibacterials, has attracted much attention in recent years. In addition to the
      well known mechanisms, such as inactivation of drugs and alteration of targets,
      active efflux is now known to play a major role in the resistance of many species
      to antibacterials. Drug-specific efflux (e.g. that of tetracycline) has been
      recognised as the major mechanism of resistance to this drug in Gram-negative
      bacteria. In addition, we now recognise that multidrug efflux pumps are becoming
      increasingly important. Such pumps play major roles in the antiseptic resistance
      of Staphylococcus aureus, and fluoroquinolone resistance of S. aureus and
      Streptococcus pneumoniae. Multidrug pumps, often with very wide substrate
      specificity, are not only essential for the intrinsic resistance of many Gram
      negative bacteria but also produce elevated levels of resistance when
      overexpressed. Paradoxically, 'advanced' agents for which resistance is unlikely
      to be caused by traditional mechanisms, such as fluoroquinolones and beta-lactams
      of the latest generations, are likely to select for overproduction mutants of
      these pumps and make the bacteria resistant in one step to practically all
      classes of antibacterial agents. Such overproduction mutants are also selected
      for by the use of antiseptics and biocides, increasingly incorporated into
      consumer products, and this is also of major concern. We can consider efflux
      pumps as potentially effective antibacterial targets. Inhibition of efflux pumps
      by an efflux pump inhibitor would restore the activity of an agent subject to
      efflux. An alternative approach is to develop antibacterials that would bypass
      the action of efflux pumps.

PMID- 14717628
TI  - The interpersonal effects of anger and happiness in negotiations.
AB  - Three experiments investigated the interpersonal effects of anger and happiness
      in negotiations. In the course of a computer-mediated negotiation, participants
      received information about the emotional state (anger, happiness, or none) of
      their opponent. Consistent with a strategic-choice perspective, Experiment 1
      showed that participants conceded more to an angry opponent than to a happy one.
      Experiment 2 showed that this effect was caused by tracking--participants used
      the emotion information to infer the other's limit, and they adjusted their
      demands accordingly. However, this effect was absent when the other made large
      concessions. Experiment 3 examined the interplay between experienced and
      communicated emotion and showed that angry communications (unlike happy ones)
      induced fear and thereby mitigated the effect of the opponent's experienced
      emotion. These results suggest that negotiators are especially influenced by
      their opponent's emotions when they are motivated and able to consider them.

PMID- 14717629
TI  - Self-verification motives at the collective level of self-definition.
AB  - Three studies examined self-verification motives in relation to collective
      aspects of the self. Several moderators of collective self-verification were also
      examined--namely, the certainty with which collective self-views are held, the
      nature of one's ties to a source of self-verification, the salience of the
      collective self, and the importance of group identification. Evidence for
      collective self-verification emerged across all studies, particularly when
      collective self-views were held with high certainty (Studies 1 and 2), perceivers
      were somehow tied to the source of self-verification (Study 1), the collective
      self was salient (Study 2), and group identification was important (Study 3). To
      the authors' knowledge, these studies are the first to examine self-verification
      at the collective level of self-definition. The parallel and distinct ways in
      which self-verification processes may operate at different levels of self
      definition are discussed.

PMID- 14717622
TI  - Comparative tolerability of sedative agents in head-injured adults.
AB  - Sedative agents are widely used in the management of patients with head injury.
      These drugs can facilitate assisted ventilation and may provide useful reductions
      in cerebral oxygen demand. However, they may compromise cerebral oxygen delivery
      via their cardiovascular effects. In addition, individual sedative agents have
      specific and sometimes serious adverse effects. This review focuses on the
      different classes of sedative agents used in head injury, with a discussion of
      their role in the context of clinical pathophysiology. While there is no sedative
      that has all the desirable characteristics for an agent in this clinical setting,
      careful titration of dose, combination of agents, and a clear understanding of
      the pathophysiology and pharmacology of these agents will allow safe sedative
      administration in head injury.

PMID- 14717630
TI  - Introduction to the special section on cognitive abilities: 100 years after
      Spearman's (1904) "'General intelligence,' objectively determined and measured".
AB  - The study of individual differences in cognitive abilities is one of the few
      branches of psychological science to amass a coherent body of empirical knowledge
      withstanding the test of time. There is wide consensus that cognitive abilities
      are organized hierarchically, and C. Spearman's (1904) general intelligence
      occupies the vertex of this hierarchy. In addition, specific abilities beyond
      general intelligence refine longitudinal forecasts of important social phenomena
      and paint a rich portrait of this important domain of psychological diversity.
      This opening article identifies and then reviews 5 major areas concerning the
      personological significance of cognitive abilities and the methods used to study
      them. In models of human behavior and important life outcomes, cognitive
      abilities are critical in more ways than social scientists realize.

PMID- 14717631
TI  - Intelligence: genetics, genes, and genomics.
AB  - More is known about the genetics of intelligence than about any other trait,
      behavioral or biological, which is selectively reviewed in this article. Two of
      the most interesting genetic findings are that heritability of intelligence
      increases throughout the life span and that the same genes affect diverse
      cognitive abilities. The most exciting direction for genetic research on
      intelligence is to harness the power of the Human Genome Project to identify some
      of the specific genes responsible for the heritability of intelligence. The next
      research direction will be functional genomics--for example, understanding the
      brain pathways between genes and intelligence. Deoxyribonucleic acid (DNA) will
      integrate life sciences research on intelligence; bottom-up molecular biological
      research will meet top-down psychological research in the brain.

PMID- 14717632
TI  - The impact of childhood intelligence on later life: following up the Scottish
      mental surveys of 1932 and 1947.
AB  - The Scottish Mental Surveys of 1932 and 1947 collected valid IQ-type test scores
      for almost everyone born in 1921 and 1936 and attending school on June 1, 1932
      (N=89,498) and June 4, 1947 (N=70,805). These surveys are described. This
      research, using the surveys' data, examined (a) the stability of intelligence
      differences across the life span, (b) the determinants of cognitive change from
      childhood to old age, and (c) the impact of childhood intelligence on survival
      and health in old age. Surviving participants of the Scottish Mental Surveys were
      tested, and the surveys' data were linked with public and health records. Novel
      findings on the stability of IQ scores from age 11 to age 80; sex differences in
      cognitive aging; the dedifferentiation hypothesis of cognitive aging; and the
      effect of childhood IQ on all-cause and specific mortality, morbidity, and
      frailty in old age are presented.

PMID- 14717633
TI  - Academic performance, career potential, creativity, and job performance: can one
      construct predict them all?
AB  - This meta-analysis addresses the question of whether 1 general cognitive ability
      measure developed for predicting academic performance is valid for predicting
      performance in both educational and work domains. The validity of the Miller
      Analogies Test (MAT; W. S. Miller, 1960) for predicting 18 academic and work
      related criteria was examined. MAT correlations with other cognitive tests (e.g.,
      Raven's Matrices [J. C. Raven, 1965]; Graduate Record Examinations) also were
      meta-analyzed. The results indicate that the abilities measured by the MAT are
      shared with other cognitive ability instruments and that these abilities are
      generalizably valid predictors of academic and vocational criteria, as well as
      evaluations of career potential and creativity. These findings contradict the
      notion that intelligence at work is wholly different from intelligence at school,
      extending the voluminous literature that supports the broad importance of general
      cognitive ability (g).

PMID- 14717634
TI  - General mental ability in the world of work: occupational attainment and job
      performance.
AB  - The psychological construct of general mental ability (GMA), introduced by C.
      Spearman (1904) nearly 100 years ago, has enjoyed a resurgence of interest and
      attention in recent decades. This article presents the research evidence that GMA
      predicts both occupational level attained and performance within one's chosen
      occupation and does so better than any other ability, trait, or disposition and
      better than job experience. The sizes of these relationships with GMA are also
      larger than most found in psychological research. Evidence is presented that
      weighted combinations of specific aptitudes tailored to individual jobs do not
      predict job performance better than GMA alone, disconfirming specific aptitude
      theory. A theory of job performance is described that explicates the central role
      of GMA in the world of work. These findings support Spearman's proposition that
      GMA is of critical importance in human affairs.

PMID- 14717635
TI  - Intelligence: is it the epidemiologists' elusive "fundamental cause" of social
      class inequalities in health?
AB  - Virtually all indicators of physical health and mental competence favor persons
      of higher socioeconomic status (SES). Conventional theories in the social
      sciences assume that the material disadvantages of lower SES are primarily
      responsible for these inequalities, either directly or by inducing psychosocial
      harm. These theories cannot explain, however, why the relation between SES and
      health outcomes (knowledge, behavior, morbidity, and mortality) is not only
      remarkably general across time, place, disease, and kind of health system but
      also so finely graded up the entire SES continuum. Epidemiologists have therefore
      posited, but not yet identified, a more general "fundamental cause" of health
      inequalities. This article concatenates various bodies of evidence to demonstrate
      that differences in general intelligence (g) may be that fundamental cause.

PMID- 14717636
TI  - A gray seal's (Halichoerus grypus) responses to experimenter-given pointing and
      directional cues.
AB  - A gray seal (Halichoerus grypus) was trained to touch a target on its left or
      right by responding to pointing signals. The authors then tested whether the seal
      would be able to generalize spontaneously to altered signals. It responded
      correctly to center pointing and head turning, center upper body turning, and off
      center pointing but not to head turning and eye movements alone. The seal also
      responded correctly to brief ipsilateral and contralateral points from center and
      lateral positions. Pointing gestures did not cause the seal to select an object
      placed centrally behind it. Like many animals in similar studies, this gray seal
      probably did not understand the referential character of these gestures but
      rather used signal generalization and experience from initial operant
      conditioning to solve these tasks.

PMID- 14717637
TI  - Budgerigars (Melopsittacus undulatus) copy virtual demonstrators in a two-action
      test.
AB  - Juvenile budgerigars (Melopsittacus undulatus) observed thin film transistor
      video playback of a virtual conspecific demonstrator using its beak to remove a
      stopper from a food box, either by pulling the object upward or by pushing it
      downward. Simultaneously (Experiment 1) or subsequently (Experiment 2), the
      observers were offered a similar stopper box and rewarded with access to food for
      each removal response, regardless of its direction. Observers of upward movement
      made a greater proportion of up responses in total and showed a stronger tendency
      to increase the proportion of up responses over test trials than observers of
      downward movement. These findings provide the first demonstration of which the
      authors are aware that birds are able not only to detect and respond to a moving
      video image but also to copy its movements.

PMID- 14717638
TI  - "Right-trunkers" and "left-trunkers": side preferences of trunk movements in wild
      Asian elephants (Elephas maximus).
AB  - In this article, the side preferences of feeding-related trunk movements of free
      ranging Asian elephants (Elephas maximus) were investigated for the first time.
      It is hypothesized that a functional asymmetry of the trunk is necessary to
      perform skillful feeding movements more efficiently. This might be connected with
      a corresponding hemispheric specialization. Video recordings of 41 wild elephants
      provided frequencies and durations of the following trunk-movement categories:
      object contact, retrieval, and reaching. In each category, individual side
      preferences were found. The strength of side preferences varied between the trunk
      movement categories and the sexes. Mean durations of retrieval and reaching
      correlated negatively with the strength of side biases. Comparing the side
      preferences in the unpaired trunk with analogous phenomena in other unpaired
      grasping organs and in primate handedness. the authors discuss possible
      explanations for the evolution of asymmetries in unpaired grasping organs.

PMID- 14717639
TI  - Salience of caller identity in rhesus monkey (Macaca mulatta) coos and screams:
      perceptual experiments with human (Homo sapiens) listeners.
AB  - Recent evidence from acoustic analysis and playback experiments indicates that
      adult female rhesus monkey (Macaca mulatta) coos are individually distinctive but
      their screams are not. In this study, the authors compared discrimination of
      individual identity in these sounds by naive human listeners who judged whether 2
      sounds had been produced by the same monkey or 2 monkeys. Each of 3 experiments
      using this same-different design showed significantly better discrimination of
      vocalizer identity from coos than from screams. Experiment 1 demonstrated the
      basic finding. Experiment 2 also tested the effect of non-identity-related scream
      variation, and Experiment 3 added a comparison with human vowel sounds. Outcomes
      suggest that acoustic structural differences in coos and screams influence
      salience of caller-identity cues, with significant implications for understanding
      the functions of these calls.

PMID- 14717640
TI  - Relative contributions of the male and the female to sexual behavior and
      reproductive success in the Japanese quail (Coturnix japonica).
AB  - Two contrasting investigative techniques provided evidence consistent with the
      interpretation that female quail (Coturnix japonica) regulate male copulatory
      behavior by the duration of their immobility and through this behavioral
      mechanism they also control the rate of fertilization of their eggs. In
      Experiment 1, copulation tests with males and females from different genetic
      lines showed that the type of female that participated in a copulatory test
      significantly influenced the latency of the male's grab, mount, and cloacal
      contact responses and also determined the efficiency of the male's copulatory
      behavior. These measures of male performance were correlated with female
      immobility in Experiment 2, which used a more homogeneous population of quail.
      Furthermore, 2 of these measures (copulatory efficiency and the latency to make
      cloacal contact) were correlated with fertilization rate.

PMID- 14717641
TI  - Rhesus macaques (Macaca mulatta) categorize unknown conspecifics according to
      their dominance relations.
AB  - The authors trained 3 adult male rhesus macaques (Macaca mulatta) to categorize
      pairs of unknown conspecifics presented in a video according to the dominance
      status of the videotaped monkeys. The subjects were trained to choose the
      dominant monkey for a category of films (e.g., films showing 1 monkey chasing
      another); then, new films were presented involving different conspecifics, and
      the monkeys' first responses to this new category of behavior (e.g., monkeys
      fighting) were taken as evidence of transfer. Two subjects were able to
      generalize categorical judgments of dominance to new films involving new
      behaviors. These findings seem to indicate that monkeys can use abstract social
      concepts and are aware of the social relationships within their group.

PMID- 14717642
TI  - Social preferences of developing guinea pigs (Cavia porcellus) from the
      preweaning to the periadolescent periods.
AB  - Preference tests in a novel environment (Experiment 1) and unobtrusive
      observations in a specialized living environment (Experiment 2) examined the
      attractiveness of various classes of conspecifics for maturing guinea pigs (Cavia
      porcellus). It was found that (a). the young continued to remain near the mother
      well beyond weaning; (b). there was increased time spent with unrelated adult
      females, but not males, after weaning; (c). male and female offspring behaved
      similarly; and (d). littermates spent considerable time with each other. These
      results provide no evidence that guinea pigs approaching sexual maturity begin to
      associate preferentially with novel animals or potential breeding partners.
      Choices were largely predictable from earlier findings of the ability of various
      classes of conspecifics to reduce hypothalamic-pituitary-adrenal activity of the
      young.

PMID- 14717643
TI  - Imitation and affordance learning by pigeons (Columba livia).
AB  - The bidirectional control procedure was used to determine whether pigeons
      (Columba livia) would imitate a demonstrator that pushed a sliding screen for
      food. One group of observers saw a trained demonstrator push a sliding screen
      door with its beak (imitation group), whereas 2 other groups watched the screen
      move independently (possibly learning how the environment works) with a
      conspecific either present (affordance learning with social facilitation) or
      absent (affordance learning alone). A 4th group could not see the screen being
      pushed (sound and odor control). Imitation was evidenced by the finding that
      pigeons that saw a demonstrator push the screen made a higher proportion of
      matching screen pushes than observers in 2 appropriate control conditions.
      Further, observers that watched a screen move without a demonstrator present made
      a significantly higher proportion of matching screen pushes than would be
      expected by chance. Thus, these pigeons were capable of affordance learning.

PMID- 14717644
TI  - Referential understanding of videos in chimpanzees (Pan troglodytes), orangutans
      (Pongo pygmaeus), and children (Homo sapiens).
AB  - Performance on identical search tasks based on cues directly perceived or
      indirectly perceived through video were compared among a group of 4 adult
      chimpanzees (Pan troglodytes), a group of 2 adult orangutans (Pongo pygmaeus),
      and a group of 36 children (between 2 and 3 years of age). Children comprehended
      directly perceived cues but had difficulty with video cues. In contrast,
      chimpanzees and 1 orangutan were successful in using video to guide their search
      for a hidden object. Two follow-up studies with 3-year-old children demonstrated
      the importance of more distinct perceptual and verbal cues in aiding children's
      understanding of video as referring to real-world events.

PMID- 14717645
TI  - Stability and flexibility in preschoolers' social networks: a dynamic analysis of
      socially directed behavior allocation.
AB  - The author studied preschoolers' social networks by investigating the allocation
      of children's social investment within and across time in a classroom of a French
      nursery school during an academic year. Observations of children's social
      exchanges during free play revealed that social behaviors were directed toward
      particular group members. After an important turnover in the peer group at the
      beginning of the school year, the social network became more structured.
      Children's strong associations were mostly same sex and small sized. Even if the
      stability of children's connections remained low, it increased over time. High
      frequency partners as well as same-sex partners were more likely to be maintained
      over time. These findings as well as conceptual and methodological issues are
      discussed from a developmental perspective.

PMID- 14717646
TI  - Use of position and feature cues in discrimination learning by the whiptail
      lizard (Cnemidophorus inornatus).
AB  - Animals use a variety of cue types to locate and discriminate objects. The ease
      with which particular cue types are learned varies across species and context. An
      enormous literature contains comparisons of spatial cue use to use of other cue
      types, but few experiments examine the ease with which various nonspatial cues
      are learned. In addition, few studies have examined cue use in reptiles. Thus,
      the authors compared whiptail lizards' (Cnemidophorus inornatus) ability to learn
      and reverse a discrimination using either position (left or right) or visual
      feature cues. Lizards learned and reversed the task using position cues faster
      and with greater accuracy than using feature cues.

PMID- 14717647
TI  - Social transmission of flavor preferences in two species of hamsters
      (Mesocricetus auratus and Phodopus campbelli).
AB  - Golden hamsters (Mesocricetus auratus) and dwarf hamsters (Phodopus campbelli)
      interacted with a conspecific demonstrator that had recently consumed a flavored
      food. When given a choice between their demonstrator's flavor and another flavor,
      the dwarf hamsters preferred the flavor their demonstrator had eaten. Golden
      hamsters did not prefer their demonstrators' diets when the demonstrators were
      unrelated adults or littermates, but they did when the demonstrator was their
      mother. Videotaping the interactions between demonstrators and observers revealed
      that adult golden hamsters did not investigate foods hoarded by their
      demonstrators whereas dwarf hamsters did. These results are interpreted in terms
      of the stimuli that activate feeding behavior systems in these 2 hamster species.

PMID- 14717648
TI  - A meta-analysis of massage therapy research.
AB  - Massage therapy (MT) is an ancient form of treatment that is now gaining
      popularity as part of the complementary and alternative medical therapy movement.
      A meta-analysis was conducted of studies that used random assignment to test the
      effectiveness of MT. Mean effect sizes were calculated from 37 studies for 9
      dependent variables. Single applications of MT reduced state anxiety, blood
      pressure, and heart rate but not negative mood, immediate assessment of pain, and
      cortisol level. Multiple applications reduced delayed assessment of pain.
      Reductions of trait anxiety and depression were MT's largest effects, with a
      course of treatment providing benefits similar in magnitude to those of
      psychotherapy. No moderators were statistically significant, though continued
      testing is needed. The limitations of a medical model of MT are discussed, and it
      is proposed that new MT theories and research use a psychotherapy perspective.

PMID- 14717649
TI  - Coming to terms with risk factors for eating disorders: application of risk
      terminology and suggestions for a general taxonomy.
AB  - The aims of the present review are to apply a recent risk factor approach (H. C.
      Kraemer et al., 1997) to putative risk factors for eating disorders, to order
      these along a timeline, and to deduce general taxonomic questions. Putative risk
      factors were classified according to risk factor type, outcome (anorexia nervosa,
      bulimia nervosa, binge-eating disorder, full vs. partial syndromes), and
      additional factor characteristics (specificity, potency, need for replication).
      Few of the putative risk factors were reported to precede the onset of the
      disorder. Many factors were general risk factors; only few differentiated between
      the 3 eating disorder syndromes. Common risk factors from longitudinal and cross
      sectional studies were gender, ethnicity, early childhood eating and
      gastrointestinal problems, elevated weight and shape concerns, negative self
      evaluation, sexual abuse and other adverse experiences, and general psychiatric
      morbidity. Suggestions are made for the conceptualization of future risk factor
      studies.

PMID- 14717650
TI  - Population stratification in the candidate gene study: fatal threat or red
      herring?
AB  - Advances in molecular genetics have provided behavioral scientists with a means
      of investigating the influence of genetic factors on human behavior.
      Unfortunately, recent candidate gene studies have produced inconsistent results,
      and a frequent scapegoat for the lack of replication across studies is the threat
      of population stratification. This review of the literature on population
      stratification suggests that the threat may be a red herring. Reliable findings
      will require improved specification and measurement of the behavioral phenotypes
      in question, a renewed focus on internal validity, and the specification and
      testing of genetic factors in the context of longitudinal multivariate models. In
      this respect, behavioral scientists are well suited to investigating genetic
      factors that influence psychological mechanisms.

PMID- 14717651
TI  - An organizing framework for collective identity: articulation and significance of
      multidimensionality.
AB  - The authors offer a framework for conceptualizing collective identity that aims
      to clarify and make distinctions among dimensions of identification that have not
      always been clearly articulated. Elements of collective identification included
      in this framework are self-categorization, evaluation, importance, attachment and
      sense of interdependence, social embeddedness, behavioral involvement, and
      content and meaning. For each element, the authors take note of different labels
      that have been used to identify what appear to be conceptually equivalent
      constructs, provide examples of studies that illustrate the concept, and suggest
      measurement approaches. Further, they discuss the potential links between
      elements and outcomes and how context moderates these relationships. The authors
      illustrate the utility of the multidimensional organizing framework by analyzing
      the different configuration of elements in 4 major theories of identification.

PMID- 14717652
TI  - Prenatal stress and risk for psychopathology: specific effects or induction of
      general susceptibility?
AB  - This review focuses on prenatal stress as a risk factor for psychopathology.
      Evidence from animal studies is summarized, and the relevance of prenatal stress
      models in animals for human studies is discussed. In the offspring of prenatally
      stressed animals, overactivity and impaired negative feedback regulation of the
      hypothalamic-pituitary-adrenal axis are consistent findings and may reflect a
      pathophysiological mechanism involved in the development of psychopathology.
      Reduced activity of the opioid GABA/benzodiazepine, serotonin, and dopamine
      systems and increased activity of the sympathico-adrenal system have been found
      as well. These alterations have been linked to a diverse spectrum of
      psychopathology. Therefore, the evidence supports the view that exposure to
      prenatal stress may result in a general susceptibility to psychopathology, rather
      than exerting a direct effect on a specific form of psychopathology.

PMID- 14717653
TI  - The sleeper effect in persuasion: a meta-analytic review.
AB  - A meta-analysis of the available judgment and memory data on the sleeper effect
      in persuasion is presented. According to this effect, when people receive a
      communication associated with a discounting cue, such as a noncredible source,
      they are less persuaded immediately after exposure than they are later in time.
      Findings from this meta-analysis indicate that recipients of discounting cues
      were more persuaded over time when the message arguments and the cue had a strong
      initial impact. In addition, the increase in persuasion was stronger when
      recipients of discounting cues had higher ability or motivation to think about
      the message and received the discounting cue after the message. These results are
      discussed in light of classic and contemporary models of attitudes and
      persuasion.

PMID- 14717654
TI  - Increased plasma non-esterified fatty acids and platelet-activating factor
      acetylhydrolase are associated with susceptibility to atherosclerosis in mice.
AB  - Animal models provide vital tools to explicate the pathogenesis of
      atherosclerosis. Accordingly, we established two atherosclerosis-prone mice
      models: (i) mice lacking the LDL (low-density lipoprotein) receptor (LDLR) and
      the ability to edit apo (apolipoprotein) B mRNA (Apobec1; designated LDb : LDLR-/
      Apobec1-/-), and (ii) mice with the LDb background, who also overexpressed human
      apoB100 (designated LTp : LDLR-/- Apobec1-/- ERhB+/+). Both LDb and LTp mice had
      markedly elevated levels of LDL and increased levels of NEFAs (non-esterified
      fatty acids) compared with C57BL/6 wild-type mice. However, fasting glucose and
      insulin levels in both animals were not different than those in C57BL/6 wild-type
      mice. It has been suggested that PAF-AH (platelet-activating factor
      acetylhydrolase) increases susceptibility to vascular disease. Both LDb and LTp
      mice had significantly higher PAF-AH mRNA levels compared with C57BL/6 wild-type
      mice. PAF-AH gene expression was also significantly influenced by age and sex.
      Interestingly, PAF-AH mRNA levels were significantly higher in both LTp male and
      female mice than in the LDb mice. This increased PAF-AH gene expression was
      associated with elevated plasma PAF-AH enzyme activities ( LTp > LDb > C57BL/6 ).
      Moreover, a greater proportion of PAF-AH activity was associated with the apoB
      containing lipoproteins: 29% in LTp and 13% in LDb mice compared with C57BL/6
      wild-type animals (6.7%). This may explain why LTp mice developed more
      atherosclerotic lesions than LDb mice by 8 months of age. In summary, increased
      plasma NEFAs, PAF-AH mRNA and enzyme activities are associated with accelerated
      atherogenesis in these animal models.

PMID- 14717655
TI  - Increased high-frequency heart rate variability during insulin-induced
      hypoglycaemia in healthy humans.
AB  - Despite causing sympathetic activation, prolonged hypoglycaemia produces little
      change in HR (heart rate) in healthy young adults. One explanation could be
      concurrent parasympathetic activation, resulting in unchanged net effects of
      autonomic influences. In the present study, hypoglycaemic (2.7 mmol/l) and
      normoglycaemic (4.7 mmol/l) hyperinsulinaemic clamp studies were performed after
      normoglycaemic baseline clamp periods with 15 healthy volunteers (seven male;
      mean age, 27 years) on two occasions in a randomized single-blind cross-over
      design. Non-invasive indices of cardiac autonomic activity and hormones were
      measured at baseline and 1 h after the beginning of hypoglycaemia or control
      normoglycaemia. Plasma insulin levels and mean HR were similar during both
      conditions. During hypoglycaemia, there was a 485% increase in plasma adrenaline
      (epinephrine). A shortening of the pre-ejection period by 45% suggested strong
      sympathetic cardiac activation. High-frequency (0.15-0.45 Hz) HRV (HR
      variability) increased, indicating a concomitant increase in parasympathetic
      tone. Thus, during hypoglycaemia-induced sympathetic cardiac activation in
      healthy adults, parasympathetic mechanisms are involved in stabilizing mean HR.

PMID- 14717656
TI  - N-terminal pro-C-type natriuretic peptide, but not C-type natriuretic peptide, is
      greatly elevated in the fetal circulation.
AB  - We have identified recently a new peptide, NT-proCNP(1-50) (N-terminal pro-C-type
      natriuretic peptide), in the circulation of humans and sheep. A previous report
      of an elevated fetal-maternal gradient in immunoreactive CNP raised the
      possibility that processing and metabolism of proCNP may differ in maternal and
      fetal tissues. We therefore collected matching peripheral maternal and umbilical
      cord plasma samples at delivery from women with normotensive and pre-eclamptic
      pregnancies to investigate the presence and concentrations of CNP and NT-proCNP
      using HPLC and RIA. Plasma concentrations of NT-proCNP in normotensive umbilical
      cord plasma were 10-fold higher than maternal venous levels (246+/-17 compared
      with 24.3+/-1.8 pmol/l; P <0.001) and much higher than corresponding levels of
      CNP (3.6+/-0.4 compared with 1.8+/-0.3 pmol/l in the fetal and maternal plasma
      respectively; P <0.001). Although there was no significant difference between
      normotensive and pre-eclamptic plasma CNP concentrations in either maternal or
      umbilical cord blood, NT-proCNP showed a significant statistical interaction ( F
      =5.8, P =0.025) between the source (maternal or fetal) and gestational group
      (normotensive or pre-eclamptic). Maternal NT-proCNP levels were raised in the pre
      eclampsia group, whereas the converse was observed in umbilical cord blood. In
      conclusion, the greatly elevated ratio of NT-proCNP/CNP in fetal compared with
      maternal plasma suggests that synthesis, as well as clearance, of CNP (but not NT
      proCNP clearance) are markedly increased in fetal tissues.

PMID- 14717657
TI  - Methotrexate induces interleukin-8 production by human bronchial and alveolar
      epithelial cells.
AB  - Methotrexate (MTX) has been widely used for the treatment of a variety of tumours
      as well as for inflammatory diseases. MTX-induced pneumonitis has been a serious
      unpredictable side effect of the treatment and an important clinical problem.
      However, its mechanism remains largely unclear. Possible causes include allergic,
      cytotoxic or immunologic reactions to this agent. To elucidate the
      proinflammatory mechanism of MTX-induced pneumonitis, we evaluated the effect of
      MTX on the production of IL (interleukin)-8 by human bronchial and alveolar
      epithelial cells in vitro and the role of p38 MAPK (mitogen-activated protein
      kinase) in order to clarify the intracellular signal regulating IL-8 expression.
      MTX induced IL-8 secretion by human bronchial and alveolar epithelial cells in a
      dose- and time-dependent manner within the range of the clinically observed serum
      concentrations. Although addition of LPS (lipopolysaccharide) and glucose showed
      no significant enhancing effect, addition of IL-1beta or TNF-alpha (tumour
      necrosis factor-alpha) with MTX to bronchial epithelial cells showed a
      significant augmenting effect. SB203580, the specific inhibitor of p38 MAPK,
      inhibited MTX-induced IL-8 production. MTX induced the phosphorylation of
      Thr(180) and Tyr(182) on p38 MAPK. These results suggest that MTX activates
      bronchial and alveolar epithelial cells to induce IL-8 production through p38
      MAPK, which might play an important role as one of the mechanisms of MTX-induced
      lung inflammation.

PMID- 14717659
TI  - Aspergillus niger mstA encodes a high-affinity sugar/H+ symporter which is
      regulated in response to extracellular pH.
AB  - A sugar-transporter-encoding gene, mstA, which is a member of the major
      facilitator superfamily, has been cloned from a genomic DNA library of the
      filamentous fungus Aspergillus niger. To enable the functional characterization
      of MSTA, a full-length cDNA was expressed in a Saccharomyces cerevisiae strain
      deficient in hexose uptake. Uptake experiments using 14C-labelled monosaccharides
      demonstrated that although able to transport D-fructose ( K(m), 4.5+/-1.0 mM), D
      xylose ( K(m), 0.3+/-0.1 mM) and D-mannose ( K(m), 60+/-20 microM), MSTA has a
      preference for D-glucose (K(m), 25+/-10 microM). pH changes associated with sugar
      transport indicate that MSTA catalyses monosaccharide/H+ symport. Expression of
      mstA in response to carbon starvation and upon transfer to poor carbon sources is
      consistent with a role for MSTA as a high-affinity transporter for D-glucose, D
      mannose and D-xylose. Northern analysis has shown that mstA is subject to CreA
      mediated carbon catabolite repression and pH regulation mediated by PacC. A.
      niger strains in which the mstA gene had been disrupted are phenotypically
      identical with isogenic reference strains when grown on 0.1-60 mM D-glucose, D
      mannose, D-fructose or D-xylose. This indicates that A. niger possesses other
      transporters capable of compensating for the absence of MSTA.

PMID- 14717660
TI  - Novozym 435-catalysed transesterification of crude soya bean oils for biodiesel
      production in a solvent-free medium.
AB  - When crude soya-bean oil was used as the source for biodiesel production, the
      yield of methyl ester was significantly lower than that from refined soya-bean
      oil. The major difference between refined and crude soya-bean oils was found to
      be due to the contents of phospholipids, free acid and water, which have varied
      influences on biodiesel production. Phospholipid content was the most influential
      factor; the higher the phospholipid content in the oil, the lower is the methyl
      ester yield. The optimal water activity was found to be in the range 0.12-0.44,
      and free acid included in crude soya-bean oils showed no negative effect on
      enzymic transesterification. During our study of three-step methanolysis of crude
      soya-bean oils for biodiesel production, we noted that the second-step
      methanolysis was much faster than the first-step reaction. On the basis of this
      finding, the proposal that immersing pretreatment of lipase in oils contributes
      to improvement in enzyme activity has been put forward. In addition, it has been
      demonstrated that immersing pretreatment of lipase in oils could improve both the
      reaction rate and methyl ester yield significantly. A methyl ester yield of 94%
      could be achieved by immersing lipase in crude oils for 120 h and this was just
      as high as the yield for refined oils.

PMID- 14717658
TI  - Heparan sulphate proteoglycans modulate fibroblast growth factor-2 binding
      through a lipid raft-mediated mechanism.
AB  - We investigated how lipid raft association of HSPG (heparan sulphate
      proteoglycans) modulates FGF-2 (fibroblast growth factor-2/basic fibroblast
      growth factor) interactions with vascular smooth-muscle cells. When lipid rafts
      were disrupted with sterol-binding agents, methyl-beta-cyclodextrin and filipin,
      FGF-2 binding to HSPG was reduced 2-5-fold, yet the amount and turnover of cell
      surface HSPG were unaffected [corrected]. Approx. 50-65% of bound FGF-2 was in
      lipid raft-associated fractions based on insolubility in cold Triton X-100 and
      flotation in OptiPrep density gradients, and this level was increased with higher
      FGF-2 concentrations [corrected]. Less FGF-2 (50-90%) was associated in raft
      fractions when cholesterol was depleted or HSPG were degraded with heparinase
      III. To investigate how lipid raft-HSPG interactions altered binding, we compared
      the rates of FGF-2 dissociation with native, MbetaCD (methyl-beta-cyclodextrin)-
      and filipin-treated cells. We found that FGF-2 dissociation rates were increased
      when lipid rafts were disrupted. These results suggest that localization of HSPG
      within lipid rafts creates high local concentrations of binding sites such that
      dissociation of FGF-2 is hindered. The localization of FGF-2 and HSPG to lipid
      rafts also correlated with the activation of protein kinase Calpha. Thus raft
      association of HSPG might create growth factor traps resulting in increased
      binding and signal transduction to enhance cell sensitivity.

PMID- 14717662
TI  - Morphological variants of plasma cell tumours.

PMID- 14717663
TI  - Assessment of apoptosis by M30 immunoreactivity and the correlation with
      morphological criteria in normal colorectal mucosa, adenomas and carcinomas.
AB  - AIMS: To investigate the monoclonal antibody M30 for the assessment of apoptosis
      in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase
      mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the
      methods most often used to demonstrate and quantify apoptosis in histological
      tissue sections, the interpretation and specificity of these techniques have been
      controversial. Immunohistochemistry using the monoclonal antibody M30 that
      recognizes caspase-cleaved cytokeratin 18 is considered to be a promising
      alternative but has yet to be validated against a generally accepted standard.
      METHODS AND RESULTS: Paraffin sections of normal colonic mucosa (n = 30), normal
      mucosa obtained from resection margins from carcinomas (n = 30), colorectal
      adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial
      cells was assessed by M30 immunoreactivity and morphological criteria and
      expressed as a proportion of the total number of cells counted (apoptotic index).
      Mean apoptotic indices using M30 were 0.18 +/- 0.04% in normal mucosa, 0.42 +/-
      0.04% in adenomas and 1.97 +/- 0.24% in carcinomas. Using morphological criteria,
      these indices were 0.23 +/- 0.03%, 0.62 +/- 0.06% and 1.78 +/- 0.19%,
      respectively. Apoptotic counts were higher in normal mucosa obtained from
      resection margins than in genuinely normal mucosa using the M30 antibody.
      Apoptotic indices obtained by M30 immunoreactivity and morphological criteria
      were positively correlated (r = 0.71, P < 0.01). CONCLUSION: Assessment of
      apoptotic cells by M30 immunoreactivity correlates well with morphological
      criteria. Apoptotic indices increase in the course of the adenoma-carcinoma
      sequence. Apoptosis in normal mucosa obtained from resection margins differs from
      genuinely normal mucosa necessitating caution when interpreting studies of
      apoptosis in normal colonic mucosa. Our findings support the use of the M30
      method in the study of apoptosis in colorectal tissues.

PMID- 14717664
TI  - Invasive micropapillary carcinoma of the breast: high incidence of lymph node
      metastasis with extranodal extension and its immunohistochemical profile compared
      with invasive ductal carcinoma.
AB  - AIMS: Invasive micropapillary carcinoma of the breast is an aggressive and
      distinctive variant of breast cancer. These tumours have a characteristic
      histological appearance and have been associated with a high incidence of
      axillary lymph node metastases and a poor clinical outcome. The aims of this
      study were to investigate the immunohistochemical profile of invasive
      micropapillary carcinoma of the breast, to compare it with invasive ductal
      carcinoma, and to identify the morphological parameters which predict its poor
      outcome. METHODS AND RESULTS: Fifty-three (2.6%) invasive micropapillary
      carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were
      identified by retrospective review. The patient age at presentation ranged from
      33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27
      mm). Eighty-two percent (43 of 53) were of high histological grade; 69% (33 of
      48) of cases with axillary lymph node dissections had positive lymph nodes; and
      75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal
      extension. Of lymph node-positive cases, 61% had four or more metastatic lymph
      nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The
      percentages of cases positive for oestrogen receptor (ER) and progesterone
      receptor (PR) were 68% and 61%, respectively. These values were significantly
      higher than the values for invasive ductal carcinomas. p53 and c-erbB-2 were
      detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%.
      Follow-up was available in 36 patients. Eight patients had local recurrences,
      nine patients had distant metastases, and 10 patients died of disease within a
      follow-up period of 9 years. CONCLUSION: Lymphotropism and an unfavourable
      prognosis are the hallmarks of this distinct entity. Prognostic markers such as
      ER, PR, p53, and c-erbB-2 failed to provide new criteria to allow discrimination
      of these tumours from other breast cancers.

PMID- 14717665
TI  - Cyclooxygenase-2 expression: a potential prognostic and predictive marker for
      high-grade ductal carcinoma in situ of the breast.
AB  - AIMS: To study cyclooxygenase-2 (COX-2) expression in ductal carcinoma in situ
      (DCIS) of the breast and its association with histological features. COX-2, an
      inducible prostaglandin synthase, has been shown to be important in mammary
      carcinogenesis, being associated with increased tumour size and unfavourable
      outcome in breast cancer. Animal studies indicate that COX-2 inhibition is
      effective in the prevention and treatment of mammary cancers. METHODS AND
      RESULTS: Fifty-one cases of DCIS diagnosed during 1990-2000 were reviewed.
      Immunohistochemistry for COX-2 was performed and the COX-2 staining scores were
      correlated with histological features. The majority of cases [41 of 51 (80%)] had
      positive COX-2 staining, of which 13 cases (25%) had strong staining. High
      nuclear grade DCIS was significantly associated with increased COX-2 staining (P
      = 0.04). CONCLUSIONS: High-grade lesions are known to be associated with a higher
      recurrence rate following excision and are often oestrogen receptor negative, and
      as such, may be less responsive to adjuvant tamoxifen therapy. There is a need to
      examine further the role of COX-2 expression in DCIS, as both a prognostic and
      predictive factor.

PMID- 14717666
TI  - Towards reasonable workload in diagnosis of sentinel lymph nodes: comparison of
      two frozen section methods.
AB  - AIMS: To compare two methods of histological assessment with intraoperative
      diagnosis of sentinel node metastases in breast cancer. METHODS AND RESULTS: A
      total of 204 consecutive breast cancer cases with lymphatic mapping, sentinel
      node biopsy and intraoperative diagnosis were included. The sentinel nodes in the
      first 102 cases (method A) were bisected and serially sectioned. In the other 102
      cases (method B) the nodes were sliced thinly with a razor blade. All 1-1.5 mm
      thick slices were mounted on prechilled mounting medium on frozen section
      buttons. Cytological imprints were also made of the attached tissue slices.
      Postoperative diagnosis of sentinel lymph node metatases was taken as gold
      standard. Sentinel node metastases were found in 28 (27%) cases in group A and in
      42 (40%) cases in group B (P = 0.05). The median size of the sentinel node
      metastases was 4.3 mm in group A and 3.3 mm in group B (P < 0.05). CONCLUSION:
      Method B finds more and smaller metastases and takes less time and effort in the
      laboratory. When using method A, many small metastases are not detected at all.

PMID- 14717667
TI  - Extensive vascular invasion is a marker of risk of relapse in encapsulated non
      Hurthle cell follicular carcinoma of the thyroid gland: a clinicopathological
      study of 18 consecutive cases from a single institution with a 11-year median
      follow-up.
AB  - AIMS: To determine the prognostic value of certain clinicopathological features
      in a series of 18 consecutive cases of encapsulated follicular carcinoma (EFC) of
      the thyroid gland with long follow-up. METHODS AND RESULTS: Eighteen consecutive
      cases of EFC were retrieved from 1975 to 1993. Gender, age at onset, type of
      surgery, presence of capsular and/or vascular invasion, number of involved
      vessels, tumour size, and TNM/pTNM classification were evaluated and correlated
      with disease outcome. None of the cases presented with distant metastases.
      Extensive vascular invasion (defined as more than four capsular vessels involved)
      was present in two cases. After a median follow-up of 133 months, all patients
      were alive. Three cases had relapsed in lung and bone. In two out of these three
      cases, extensive vascular invasion was present. Radioiodine therapy was curative
      in two of three of the relapsed cases. CONCLUSIONS: EFC is a low-risk carcinoma,
      with no patients' deaths after a median follow-up of 11 years. Extensive vascular
      invasion should be considered as a risk factor for relapse. A conservative
      surgical approach is recommended. Since relapses may occur up to 14 years after
      the initial surgery, life-long follow-up is advisable.

PMID- 14717668
TI  - Epithelioid haemangiosarcoma of the thyroid gland. Report of six cases from a non
      Alpine region.
AB  - AIM: To report a series of six cases of thyroid haemangiosarcoma (HAS) from a non
      Alpine region. METHODS AND RESULTS: The patients were four females and two males,
      aged 54-81 years (average 68 years). The tumours presented as large haemorrhagic
      masses (diameter 40-70 mm, average 56 mm) with extensive necrosis.
      Histologically, they were composed of polymorphous epithelioid cells with
      vesicular nuclei and abundant eosinophilic cytoplasm with occasional
      intracytoplasmic lumina. Mitotic activity was high. Tumor cells expressed
      vimentin (6/6), CD31 (6/6), FVIII (5/6), CD34 (2/6), and cytokeratins (5/6). One
      tumour (1/6) over-expressed p53 protein in more than 20% of cells.
      Ultrastructurally, Weibel-Palade bodies were present (4/6). Clinical follow-up of
      four patients (range 3-24 months, median 9 months) showed that two of them have
      died of the disease 0.5 and 3 months after diagnosis, one died of unrelated
      causes (with 24 months' uneventful follow-up) and one is alive 21 months after
      operation with no evidence of disease. CONCLUSIONS: Although thyroid HAS is
      usually regarded as an extremely aggressive neoplasm with a dismal prognosis
      similar to anaplastic carcinoma, one of our cases suggests that HAS can behave in
      a less aggressive way. The morphological, immunohistochemical and ultrastructural
      findings support the hypothesis that thyroid HAS is a distinct entity, unrelated
      to other thyroid malignancies.

PMID- 14717669
TI  - Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined
      according to the new 1999 WHO/IASLC criteria: a preliminary study.
AB  - AIMS: The World Health Organization classification of bronchial intraepithelial
      neoplastic lesions has been shown to be reproducible. However little is known
      about its biological value. The aim of this study was to assess the proliferative
      activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in
      situ (CIS) by the expression of Ki67 on biopsy specimens obtained during
      fluorescence bronchoscopy. METHODS AND RESULTS: The percentage of Ki67+ lesional
      nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters
      (defined as a group of at least two strongly Ki67+ nuclei located in the upper
      third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended
      on the proportion of the stained nuclei and on the intensity of staining. MiD,
      MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and
      40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and
      100% CIS showed one or more positive clusters. When only multiple clusters were
      considered the difference between high- and low-grade lesions was accentuated.
      Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD
      (15%) and MoD (22%). This difference was statistically significant (P < 0.01).
      Evaluation of the Ki67 score was in line with the above results: high grade
      lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD
      versus SD plus CIS). CONCLUSIONS: Ki67 expression increases from MiD to CIS with
      a statistically significant difference between MiD plus MoD and SD plus CIS.
      These results suggest that, in terms of Ki67 positivity, SD behaves like CIS
      rather than like MiD or MoD.

PMID- 14717670
TI  - Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL
      in resected non-small-cell lung cancers.
AB  - AIMS: Some experimental evidence suggests that in lung cancer, development,
      progression and an increased proliferation rate can be linked to apoptosis
      related factors. In this study we evaluated the possible role of p53 and Bcl-2
      gene family members as prognostic factors for non-small-cell lung cancer. METHODS
      AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2
      gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer
      specimens to establish the role of these genes in lung cancer pathogenesis, and
      to evaluate their prognostic importance. The expression of Bcl-2 was correlated
      with a shorter patient survival time and with the nodal status of the neoplasm.
      We also found frequent over-expression of bax and Bcl-xL to be of no prognostic
      significance. Finally, we found no correlation between frequent detection of
      aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with
      patient survival time. CONCLUSIONS: This study confirms a relevant role for
      apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights
      the possible role of Bcl-2 as a prognostic factor for this tumour.

PMID- 14717671
TI  - Carcinomas arising in multilocular thymic cysts of the neck: a
      clinicopathological study of three cases.
AB  - AIMS: To report three cases of primary carcinoma of the neck arising in
      multilocular thymic cysts (MTC). METHODS AND RESULTS: The patients were three men
      aged 47, 50 and 52 years who presented with a painless neck mass of several
      weeks' duration. The patients had no history of previous surgical procedures or
      of malignancy elsewhere. The tumours in all three patients were located on the
      right lateral side of the neck; all patients underwent complete surgical
      resection of the mass. Grossly, the tumours were cystic and measured between 20
      and 30 mm in greatest diameter. Histologically, the tumours showed cyst walls
      lined by squamous epithelium. The cyst walls contained prominent germinal centres
      with lymphoid hyperplasia, cholesterol cleft granulomas, and scattered
      keratinized structures reminiscent of Hassall's corpuscles. In addition, a
      neoplastic cellular proliferation composed of round to oval cells arranged in
      sheets and originating from the lining of the cystic structures was present. The
      neoplastic cells showed moderate amounts of eosinophilic cytoplasm, round nuclei,
      and, in some areas, prominent nucleoli. Mitotic figures were easily found, and
      cellular pleomorphism was present in several areas. In two cases the tumours
      showed features of basaloid carcinoma of the thymus, while in one case the
      pattern was that of squamous cell carcinoma. Immunohistochemical studies for
      keratin showed a strong positive reaction in the tumour cells, while leucocyte
      common antigen strongly stained the lymphoid background. Follow-up information
      obtained in two patients showed them to be alive 6 months after initial
      diagnosis. One patient was lost to follow-up. CONCLUSION: The cases described
      here represent an unusual variant of carcinoma arising in multilocular thymic
      cyst in the neck region.

PMID- 14717672
TI  - Pyothorax-associated lymphoma (PAL): a western case with marked angiocentricity
      and review of the literature.
AB  - AIMS: To report a case of pyothorax-associated lymphoma in a non
      immunocompromised 78-year-old man with a 45-year history of tuberculous pleuritis
      and left pleural effusion. Pyothorax-associated lymphoma is a high-grade non
      Hodgkin's lymphoma occurring in 2% of patients with long-standing tuberculous
      pleuritis and pyothorax. Pyothorax-associated lymphoma is frequently Epstein-Barr
      virus (EBV)-associated, mainly reported in Japan but exceedingly rare in western
      countries. METHODS AND RESULTS: Histology revealed a high-grade, diffuse large B
      cell lymphoma with immunoblastic and plasmacytoid features and marked
      angiocentricity with focal destruction of the vessel walls. Immunohistochemistry
      revealed a post germinal B-cell phenotype. RNA in-situ hybridization and
      molecular analysis showed a latent EBV infection and absence of human herpes
      virus-8 (HHV-8). CONCLUSIONS: Pyothorax-associated lymphoma represents a rare but
      distinctive type of diffuse large B-cell lymphoma, with characteristic clinico
      epidemiological, immunohistological, and biological features.

PMID- 14717673
TI  - CD117 expression in oesophageal carcinosarcoma: a potential diagnostic pitfall.

PMID- 14717674
TI  - Experience from the use of telepathology in Telemark.

PMID- 14717675
TI  - The autopsy.

PMID- 14717676
TI  - A peculiar case of precursor B lymphoblastic leukaemia/lymphoma histologically
      mimicking diffuse large B-cell lymphoma.

PMID- 14717677
TI  - Calcifying fibrous pseudotumour: first case report in the gallbladder.

PMID- 14717678
TI  - Eosinophilic granular cell change of Sertoli cells and of epididymal columnar
      cells.

PMID- 14717679
TI  - Loss of Fhit protein in carcinoma of primary and secondary mullerian systems.

PMID- 14717680
TI  - Gastrointestinal stromal tumour (GIST) masquerading as linitis plastica.

PMID- 14717681
TI  - Mucinous metaplasia of the glans penis.

PMID- 14717682
TI  - Soft tissue osteoma: tumour entity or reactive lesion? Paraarticular soft tissue
      osteoma of the hip.

PMID- 14717683
TI  - The influence of providing a clinical practice guideline on dental students'
      decision making.
AB  - The aim of this study was to assess the effect of the provision of a clinical
      practice guideline (CPG) on dental students' decisions to remove asymptomatic,
      impacted lower third molars. All dental students, who in 2001 were in the 3rd,
      4th or 5th (final) year of their study at the Nijmegen College of Dental
      Sciences, were invited to participate. A pre-test-post-test control group design
      was used. Given 36 patient cases, all dental students were asked to assess the
      need for removal of asymptomatic, impacted lower third molars. All pre-test
      respondents were randomly allocated to the control or intervention group. After
      the provision of a CPG to the intervention group, both groups were asked to
      assess the same cases again. Frequencies of decisions to remove the third molars
      were calculated. Chi-square tests and anova were used to test the influence of
      study year and gender on the drop-out rate and on the effect of the provision of
      a CPG on students' treatment decisions. The decrease in indications to remove
      third molars by the intervention group was statistically significant (P < 0.05).
      In the control group, no significant decrease was observed. It was concluded that
      the provision of a CPG significantly influences dental students' decision making
      about treatment in a third-molar decision task. Students who used the CPG showed
      more guideline-conformed decision making.

PMID- 14717684
TI  - Teaching received in caries prevention and perceived need for Best Practice
      Guidelines among recent graduates in Finland.
AB  - The present study evaluated teaching that recent graduates in Finland had
      received in caries prevention and their perceived need for updated Best Practice
      Guidelines. A two-page questionnaire was mailed to all dentists in Finland who
      had graduated from 1995 to 1998 (n = 390). After one reminder, the response rate
      was 46%. The closed questions covered teaching in 14 caries-preventive methods
      and its suggestions as to when and on whom to apply such methods. Each dentist's
      own opinion on the three most important methods for caries prevention in patients
      with various types of dentition was sought in open questions. The respondents
      reported that at dental school, on average 12.5 (SD = 2.4) of 14 aspects of
      caries prevention were covered in theoretical teaching, 5.5 (SD = 3.8) in
      demonstrations and 8.5 (SD = 3.0) in clinical training. The top four methods
      teaching suggested for every patient were toothbrushing (100%), use of
      fluoridated toothpaste (99%), interdental cleaning (98%), and use of xylitol
      (97%); followed by fluoride varnish (77%) and fissure sealants (54%). The three
      caries-preventive methods the respondents felt to be most useful were the same
      for all types of dentitions, in order of importance: (i) toothbrushing and use of
      fluoridated toothpaste, (ii) supplementary use of fluorides at home and (iii)
      healthy dietary habits, in particular, avoidance of sucrose. As regards clinical
      work, such teaching had served the respondents' real-life needs in patients'
      caries prevention either extremely (44%) or moderately (54%) well; 91% said,
      however, that they would benefit from nationwide Best Practice Guidelines. In
      conclusion, the recent graduates' emphasis on patient-active methods in caries
      prevention may indicate a change in the current policy favouring patient-passive
      methods.

PMID- 14717685
TI  - A cost-effective simulation curriculum for preclinical endodontics.
AB  - A challenge in contemporary dental education is to achieve a smooth transition
      from preclinical teaching environments to patient-care clinics in a cost
      effective manner. The preclinical endodontic courses at The University of Texas,
      Dental Branch at Houston provide a unique learning environment that enables the
      student to perform endodontic treatment on extracted teeth in a typodont, and be
      involved in diagnosis and treatment-planning discussions. The specially designed
      stone typodont used has built-in radiographic capability, and is mounted at each
      chair in the clinic. During each preclinical session, students are assigned
      clinical cubicles and proper aseptic protocol is followed. Students are required
      to wear gloves, masks and eyewear, and place a rubber dam during treatment.
      Written self-assessment evaluations based upon prescribed criteria are utilised;
      feedback is given by faculty composed of both full-time endodontists and graduate
      students who periodically rotate and are calibrated on a regular basis. In the
      lecture phase, clinical case scenarios are presented to reinforce concepts of
      diagnosis and emergency care and to help integrate endodontics with other
      disciplines; a Socratic-like teaching style is established by the faculty
      facilitator to create an environment for developing critical-thinking and problem
      solving skills. The overall feedback from graduating students has been very
      positive. Advantages of this format are an easier transition to patient
      management, a more keen interest in specialsation and a perceived increase in
      levels of confidence.

PMID- 14717686
TI  - Internal medicine education in dentistry: knowledge required varies according to
      dental specialty.
AB  - BACKGROUND: With recent increases in the number of elderly and medically
      compromised patients, dentists are required to have a more comprehensive
      understanding of medical problems. There is, however, little awareness of the
      importance of internal medicine at dental schools in Japan. OBJECTIVE: The aims
      of the present study were to examine whether dentists need medical knowledge, to
      examine how often they experience difficulties regarding internal medicine in
      dental practice, and to determine whether their specialty or career influences
      their needs or difficulties. DESIGN: A questionnaire based on the above
      objectives was designed and was sent to all the faculty members in the department
      of dentistry at Tsurumi University and all dentists who work at the university
      hospital. RESULTS: Of 408 surveys, 307 (75%) responded. Ninety-nine per cent of
      respondents recognized the necessity of internal medicine. The dentists
      specializing in gerodontology, dental anesthesiology or oral and maxillofacial
      surgery (group S) felt the need of knowledge of internal medicine more frequently
      than those of other specialties (group O) (Odds ratio 17.5, 95% CI: 2.4
      approximately 129.9; P = 0.000). Seventy-four per cent of the dentists
      experienced difficulties in day-to-day practice caused by a lack of medical
      knowledge. Those in group S, experienced difficulties more frequently than those
      in group O (Odds ratio 5.3, 95% CI: 2.1 approximately 12.9; P = 0.000). While the
      more experienced dentists in group S encountered difficulties more often, the
      more experienced dentists in group O encountered difficulties less often.
      CONCLUSIONS: The need for instruction in internal medicine varies according to
      dental specialty. Even very experienced dentists might fail to find solutions
      because of a lack of knowledge of internal medicine.

PMID- 14717687
TI  - Appraisal of psychomotor skills of dental students at University Complutense of
      Madrid.
AB  - The aim of this study was to evaluate the psychomotor skills of the dental
      students at University Complutense of Madrid (UCM), using a battery of
      psychometric tests. The sample comprised 306 students of the 1st, 2nd, 3rd and
      4th years of Odontology, who, during the last month of the academic term, took
      the test on rotation of solid shapes, the Embedded Figures test in its group form
      (GEFT), the O'Connor Tweezer test, the MacQuarrie test for mechanical ability and
      the indirect vision test. Before these tests began, some personal data of all
      students were collected. The results showed some statistically significant
      correlation between several personal variables (sex, manual dominance and
      previous skills) and performance in the psychometric tests, although no
      significant relation was found between these variables and the students' academic
      qualifications. When comparisons were made between the psychomotor tests and the
      academic results of the students, significant differences appeared in the tracing
      and dotting subtests of the MacQuarrie test, whereby those students with higher
      practical qualifications reached the best punctuation. In the O'Connor Tweezer
      test, the students who obtained the worst results were those with lower
      qualifications. These data could serve to detect at an early stage those students
      who need greater educational support. No relation was found between the GEFT and
      the indirect vision test.

PMID- 14717688
TI  - Outcome assessment of the French internship graduate programme.
AB  - In 1995, the first dental postgraduate residency programme was established in
      France. Selection of the applicants was performed by means of a selective
      national competitive examination among dental students in the final year of the
      undergraduate studies. The main objective of this 3-year general practice
      internship was to provide a clinical training for future academic dentists. This
      study describes the characteristics and the professional outcome of the student
      population enrolled in this programme. The French internship programme represents
      a new and welcome modification on the training of future dental academicians and
      establishes similarities with other programmes in Europe.

PMID- 14717689
TI  - Looking for caries...? Teachers evaluate a program to improve caries diagnosis
      from radiographs.
AB  - We developed a computer-assisted learning (CAL) program to improve student caries
      diagnosis from bitewing radiographs. In order to decide on its appropriateness,
      dental teachers independently evaluated the program before it was introduced. Our
      objective was to describe an evaluation by the teachers of the CAL diagnostic
      module and to compare the diagnostic performance with the evaluation score of the
      program. Key dental teachers involved in teaching clinical caries diagnosis and
      epidemiology (n = 22) viewed the CAL program. They evaluated aspects of the
      program by scoring 10 criteria on a visual analogue scale. Measures of the
      teachers' initial diagnostic accuracy assessed during use of the program were:
      sensitivity and specificity for the presence of dentine caries. Using Pearson's
      correlation coefficients, these measures of the teachers' diagnostic accuracy
      were compared separately with their evaluation score of one aspect of the
      program: the overall functionality of the program for a 2nd-year dental student.
      The teachers' mean sensitivity for dentine caries diagnosis was 76.5% (median
      77.8%; SD 15.4%) and the mean specificity was 93.7% (median 94.2%; SD 3.9%). The
      teachers gave the program a mean overall functionality score of 68% (median
      75.1%; SD 21%). Dentists with a lower sensitivity (P = 0.065) for dentine caries
      tended to give the CAL program a higher overall functionality score than the
      other teachers. The CAL program was valued as generally useful. It tended to be
      more highly valued by the dentists with initially lower scores for diagnostic
      accuracy.

PMID- 14717690
TI  - Instructional multimedia program versus standard lecture: a comparison of two
      methods for teaching the undergraduate orthodontic curriculum.
AB  - AIM: To compare the effectiveness of an interactive multimedia courseware package
      versus standard lectures regarding knowledge, understanding, and transfer of
      content, as well as problem-solving skills in orthodontics. METHODS: Pre- and
      post-test assessments of final-year dental students (n = 26), who either used an
      interactive multimedia courseware package (n = 15) or attended standard lectures
      (n = 11) on equivalent material of the undergraduate orthodontic curriculum were
      carried out. Both groups were tested by written and multiple-choice questions
      covering knowledge, understanding, and application areas in the curriculum. A one
      way anova was carried out in order to check statistical difference between the
      two groups. The P-value was set at 0.05. RESULTS: There was no difference in
      prior knowledge between the groups at baseline. Generally, no significant
      difference was seen between the two groups in relation to answers to questions
      about knowledge, understanding, and application in the orthodontic curriculum.
      However, both groups improved their scores after the course. In one question
      investigating the extent of understanding the instructional content of the
      multidisciplinary orthodontic treatment, the multimedia courseware package group
      scored significantly better. CONCLUSION: In this study, the instructional
      interactive multimedia program was found to be at least as effective as the
      standard lecture of the orthodontic curriculum for undergraduate training in
      orthodontics.

PMID- 14717691
TI  - The lysozyme of the starfish Asterias rubens. A paradygmatic type i lysozyme.
AB  - On the basis of a partial N-terminal sequence, Jolles and Jolles previously
      proposed that the lysozyme from the starfish Asterias rubens represents a new
      form of lysozyme, called type i (invertebrate) lysozyme. Indeed, it differed from
      both the types c (chicken) and g (goose) known in other animals, as well as from
      plant and phage lysozymes. Recently, several proteins belonging to the same
      family have been isolated from protostomes. Here we report the complete mature
      protein sequence and cDNA sequence of the lysozyme from Asterias. These sequences
      vindicate the previously proposed homology between the starfish, a deuterostome,
      and protostome lysozymes. In addition, we present a structural analysis that
      allows us to postulate upon the function of several conserved residues.

PMID- 14717692
TI  - Mechanisms of internalization and recycling of the chemokine receptor, CCR5.
AB  - CCR5 is a G protein-coupled receptor that binds several natural chemokines but it
      is also a coreceptor for the entry of M tropic strains of HIV-1 into cells.
      Levels of CCR5 on the cell surface are important for the rate of HIV-1 infection
      and are determined by a number of factors including the rates of CCR5
      internalization and recycling. Here we investigated the involvement of the actin
      cytoskeleton in the control of ligand-induced internalization and recycling of
      CCR5. Cytochalasin D, an actin depolymerizing agent, inhibited chemokine-induced
      internalization of CCR5 and recycling of the receptor in stably transfected CHO
      cells and in the monocytic cell line, THP-1. CCR5 internalization and recycling
      were inhibited by Toxin B and C(3) exoenzyme treatment in CHO and THP-1 cells,
      confirming activation of members of the RhoGTPase family by CCR5. The specific
      Rho kinase inhibitor Y27632, however, had no effect on CCR5 internalization or
      recycling. Ligand-induced activation of CCR5 leads to Rho kinase-dependent
      formation of focal adhesion complexes. These data indicate that CCR5
      internalization and recycling are regulated by actin polymerization and
      activation of small G proteins in a Rho-dependent manner.

PMID- 14717693
TI  - Mutational and computational analysis of the role of conserved residues in the
      active site of a family 18 chitinase.
AB  - Glycoside hydrolysis by retaining family 18 chitinases involves a catalytic acid
      (Glu) which is part of a conserved DXDXE sequence motif that spans strand four of
      a (betaalpha)8 barrel (TIM barrel) structure. These glycoside hydrolases are
      unusual in that the positive charge emerging on the anomeric carbon after
      departure of the leaving group is stabilized by the substrate itself (the N
      acetyl group of the distorted -1 sugar), rather than by a carboxylate group on
      the enzyme. We have studied seven conserved residues in the catalytic center of
      chitinase B from Serratia marcescens. Putative roles for these residues are
      proposed on the basis of the observed mutational effects, the pH-dependency of
      these effects, pKa calculations and available structural information. The results
      indicate that the pKa of the catalytic acid (Glu144) is 'cycled' during catalysis
      as a consequence of substrate-binding and release and, possibly, by a back and
      forth movement of Asp142 between Asp140 and Glu144. Rotation of Asp142 towards
      Glu144 also contributes to an essential distortion of the N-acetyl group of the 
      1 sugar. Two other conserved residues (Tyr10 and Ser93) are important because
      they stabilize the charge on Asp140 while Asp142 points towards Glu144. Asp215,
      lying opposite Glu144 on the other side of the scissile glycosidic bond,
      contributes to catalysis by promoting distortion of the -1 sugar and by
      increasing the pKa of the catalytic acid. The hydroxyl group of Tyr214 makes a
      major contribution to the positioning of the N-acetyl group of the -1 sugar.
      Taken together, the results show that catalysis in family 18 chitinases depends
      on a relatively large number of (partly mobile) residues that interact with each
      other and the substrate.

PMID- 14717694
TI  - Structural properties of the protein SV-IV.
AB  - We have investigated the molecular mechanisms that produce different structural
      and functional behavior in the monomeric and trimeric forms of seminal vesicle
      protein no. 4, a protein with immunomodulatory, anti-inflammatory, and
      procoagulant activity secreted from the rat seminal vesicle epithelium. The
      monomeric and trimeric forms were characterized in solution by CD. Details of the
      self-association process and structural changes that accompany aggregation were
      investigated by different experimental approaches: trypsin proteolysis, sequence
      analysis, chemical modification, and computer modeling. The self-association
      process induces conformational change mainly in the 1-70 region, which appears to
      be without secondary structure in the monomer but contains alpha-helix in the
      trimer. In vivo, proteolysis of seminal vesicle protein no. 4 generates active
      peptides and this is affected by the monomer/trimer state, which is regulated by
      the concentration of the protein. The information obtained shows how
      conformational changes between the monomeric and trimeric forms represent a
      crucial aspect of activity modulation.

PMID- 14717695
TI  - Localization, purification and properties of a tetrathionate hydrolase from
      Acidithiobacillus caldus.
AB  - The moderately thermophilic bacterium Acidithiobacillus caldus is found in
      bacterial populations in many bioleaching operations throughout the world. This
      bacterium oxidizes elemental sulfur and other reduced inorganic sulfur compounds
      as the sole source of energy. The purpose of this study was to purify and
      characterize the tetrathionate hydrolase of A. caldus. The enzyme was purified
      16.7-fold by one step chromatography using a SP Sepharose column. The purified
      enzyme resolved into a single band in 10% polyacrylamide gel, both under
      denaturing and native conditions. Its homogeneity was confirmed by N-terminal
      amino acid sequencing. Tetrathionate hydrolase was shown to be a homodimer with a
      molecular mass of 103 kDa (composed from two 52 kDa monomers). The purified
      enzyme had optimum activity at pH 3.0 and 40 degrees C and an isoelectric point
      of 9.8. The periplasmic localization of the enzyme was determined by differential
      fractionation of A. caldus cells. Detected products of the tetrathionate
      hydrolase reaction were thiosulfate and pentathionate as confirmed by RP-HPLC
      analysis. The activity of the purified enzyme was drastically enhanced by
      divalent metal ions.

PMID- 14717696
TI  - O-acetylation and de-O-acetylation of sialic acids in human colorectal carcinoma.
AB  - A decrease in the level of O-acetylated sialic acids observed in colorectal
      carcinoma may lead to an increase in the expression of sialyl Lewis(X), a tumor
      associated antigen, which is related to progression of colorectal cancer to
      metastasis. The underlying mechanism for this reduction is, however, not fully
      understood. Two enzymes are thought to be primarily responsible for the turnover
      of O-acetyl ester groups on sialic acids; sialate-O-acetyltransferase (OAT) and
      sialate-O-acetylesterase (OAE). We have previously reported the characterization
      of OAT activity from normal colon mucosa, which efficiently O-acetylates CMP
      Neu5Ac exclusively in the Golgi apparatus prior to the action of
      sialyltransferase. In this report we describe the identification of a lysosomal
      and a cytosolic OAE activity in human colonic mucosa that specifically hydrolyses
      9-O-acetyl groups on sialic acid. Utilizing matched resection margin and cancer
      tissue from colorectal carcinoma patients we provide strong evidence suggesting
      that the level of O-acetylated sialic acids present in normal and diseased human
      colon may be dependent on the relative activities of OAT to lysosomal OAE.
      Furthermore, we show that the level of free cytosolic Neu5,9Ac2 in human colon is
      regulated by the relative activity of the cytosolic OAE.

PMID- 14717697
TI  - Some properties of human small heat shock protein Hsp20 (HspB6).
AB  - Human heat shock protein of apparent molecular mass 20 kDa (Hsp20) and its
      mutant, S16D, mimicking phosphorylation by cyclic nucleotide-dependent protein
      kinases, were cloned and expressed in Escherichia coli. The proteins were
      obtained in a homogeneous state without utilization of urea or detergents. On
      size exclusion chromatography at neutral pH, Hsp20 and its S16D mutant were
      eluted as symmetrical peaks with an apparent molecular mass of 55-60 kDa.
      Chemical crosslinking resulted in the formation of dimers with an apparent
      molecular mass of 42 kDa. At pH 6.0, Hsp20 and its S16D mutant dissociated, and
      were eluted in the form of two peaks with apparent molecular mass values of 45-50
      and 28-30 kDa. At pH 7.0-7.5, the chaperone activity of Hsp20 (measured by its
      ability to prevent the reduction-induced aggregation of insulin or heat-induced
      aggregation of yeast alcohol dehydrogenase) was similar to or higher than that of
      commercial alpha-crystallin. Under these conditions, the S16D mutant of Hsp20
      possessed lower chaperone activity than the wild-type protein. At pH 6.0, both
      alpha-crystallin and Hsp20 interacted with denatured alcohol dehydrogenase;
      however, alpha-crystallin prevented, whereas Hsp20 either did not affect or
      promoted, the heat-induced aggregation of alcohol dehydrogenase. The mixing of
      wild-type human Hsp27 and Hsp20 resulted in a slow, temperature-dependent
      formation of hetero-oligomeric complexes, with apparent molecular mass values of
      100 and 300 kDa, which contained approximately equal amounts of Hsp27 and Hsp20
      subunits. Phosphorylation of Hsp27 by mitogen activated protein kinase-activated
      protein kinase 2 was mimicked by replacing Ser15, 78 and 82 with Asp. A 3D mutant
      of Hsp27 mixed with Hsp20 rapidly formed a hetero-oligomeric complex with an
      apparent molecular mass of 100 kDa, containing approximately equal quantities of
      two small heat shock proteins.

PMID- 14717698
TI  - Surface nucleolin participates in both the binding and endocytosis of lactoferrin
      in target cells.
AB  - Lactoferrin (Lf), a multifunctional molecule present in mammalian secretions and
      blood, plays important roles in host defense and cancer. Indeed, Lf has been
      reported to inhibit the proliferation of cancerous mammary gland epithelial cells
      and manifest a potent antiviral activity against human immunodeficiency virus and
      human cytomegalovirus. The Lf-binding sites on the cell surface appear to be
      proteoglycans and other as yet undefined protein(s). Here, we isolated a Lf
      binding 105 kDa molecular mass protein from cell extracts and identified it as
      human nucleolin. Medium-affinity interactions ( approximately 240 nm) between Lf
      and purified nucleolin were further illustrated by surface plasmon resonance
      assays. The interaction of Lf with the cell surface-expressed nucleolin was then
      demonstrated through competitive binding studies between Lf and the anti-human
      immunodeficiency virus pseudopeptide, HB-19, which binds specifically surface
      expressed nucleolin independently of proteoglycans. Interestingly, binding
      competition studies between HB-19 and various Lf derivatives in proteoglycan
      deficient hamster cells suggested that the nucleolin-binding site is located in
      both the N- and C-terminal lobes of Lf, whereas the basic N-terminal region is
      dispensable. On intact cells, Lf co-localizes with surface nucleolin and together
      they become internalized through vesicles of the recycling/degradation pathway by
      an active process. Morever, a small proportion of Lf appears to translocate in
      the nucleus of cells. Finally, the observations that endocytosis of Lf is
      inhibited by the HB-19 pseudopeptide, and the lack of Lf endocytosis in
      proteoglycan-deficient cells despite Lf binding, point out that both nucleolin
      and proteoglycans are implicated in the mechanism of Lf endocytosis.

PMID- 14717699
TI  - Biochemical and molecular characterization of a laccase from the edible straw
      mushroom, Volvariella volvacea.
AB  - We have isolated a laccase (lac1) from culture fluid of Volvariella volvacea,
      grown in a defined medium containing 150 micro m CuSO4, by ion-exchange and gel
      filtration chromatography. Lac1 has a molecular mass of 58 kDa as determined by
      SDS/PAGE and an isoelectric point of 3.7. Degenerate primers based on the N
      terminal sequence of purified lac1 and a conserved copper-binding domain were
      used to generate cDNA fragments encoding a portion of the lac1 protein and RACE
      was used to obtain full-length cDNA clones. The cDNA of lac1 contained an ORF of
      1557 bp encoding 519 amino acids. The amino acid sequence from Ala25 to Asp41
      corresponded to the N-terminal sequence of the purified protein. The first 24
      amino acids are presumed to be a signal peptide. The expression of lac1 is
      regulated at the transcription level by copper and various aromatic compounds. RT
      PCR analysis of gene transcription in fungal mycelia grown on rice-straw revealed
      that, apart from during the early stages of substrate colonization, lac1 was
      expressed at every stage of the mushroom developmental cycle defined in this
      study, although the levels of transcription varied considerably depending upon
      the developmental phase. Transcription of lac1 increased sharply during the
      latter phase of substrate colonization and reached maximum levels during the very
      early stages (primordium formation, pinhead stage) of fruit body morphogenesis.
      Gene expression then declined to approximately 20-30% of peak levels throughout
      the subsequent stages of sporophore development.

PMID- 14717700
TI  - A single mutation that causes phosphatidylglycerol deficiency impairs synthesis
      of photosystem II cores in Chlamydomonas reinhardtii.
AB  - Two mutants of Chlamydomonas reinhardtii, mf1 and mf2, characterized by a marked
      reduction in their phosphatidylglycerol content together with a complete loss in
      its Delta3-trans hexadecenoic acid-containing form, also lost photosystem II
      (PSII) activity. Genetic analysis of crosses between mf2 and wild-type strains
      shows a strict cosegregation of the PSII and lipid deficiencies, while phenotypic
      analysis of phototrophic revertant strains suggests that one single nuclear
      mutation is responsible for the pleiotropic phenotype of the mutants. The nearly
      complete absence of PSII core is due to a severely decreased synthesis of two
      subunits, D1 and apoCP47, which is not due to a decrease in translation
      initiation. Trace amounts of PSII cores that were detected in the mutants did not
      associate with the light-harvesting chlorophyll a/b-binding protein antenna
      (LHCII). We discuss the possible role of phosphatidylglycerol in the coupled
      process of cotranslational insertion and assembly of PSII core subunits.

PMID- 14717701
TI  - Spatio-temporal distribution of cellular retinol-binding protein gene transcripts
      (CRBPI and CRBPII) in the developing and adult zebrafish (Danio rerio).
AB  - We have cloned and determined the nucleotide sequence of the cDNA coding for a
      cellular retinol-binding protein type I (CRBPI) from zebrafish. The deduced amino
      acid sequence of the zebrafish CRBPI showed highest sequence identity (
      approximately 59%) to the mammalian CRBPIs of the intracellular lipid-binding
      protein (iLBP) multigene family. Phylogenetic analysis clustered the zebrafish
      CRBPI to the CRBPI clade. The zebrafish CRBPI gene (rbp1) and CRBPII gene (rbp2)
      both consist of four exons separated by three introns, identical to all other
      iLBP genes in vertebrates. Two transcription start sites were identified in the
      rbp1 promoter and a single transcription start site was identified for rbp2.
      Radiation hybrid mapping assigned the zebrafish rbp1 gene to linkage group 16 and
      conserved syntenic genes were found by comparative analysis of mammalian
      orthologous rbp1 genes. RT-PCR detected mRNA transcripts in the adult intestine,
      liver, brain, ovary and testis for rbp1 gene and in the intestine and liver for
      rbp2 gene. Whole mount in situ hybridization of zebrafish embryos revealed rbp1
      mRNA expression in the developing zebrafish central nervous system at specific
      sites that are known to have abundant retinoic acid distribution and significant
      retinoic acid action. Whole mount in situ hybridization also showed that the
      zebrafish rbp2 mRNA was localized specifically in the embryonic intestinal bulb
      and the developing intestine during the larval stage, implying a novel function
      for the rbp2 gene product during organogenesis and development of the zebrafish
      intestine.

PMID- 14717702
TI  - GTP cyclohydrolase I utilizes metal-free GTP as its substrate.
AB  - GTP cyclohydrolase I (GCH) is the rate-limiting enzyme for the synthesis of
      tetrahydrobiopterin and its activity is important in the regulation of monoamine
      neurotransmitters such as dopamine, norepinephrine and serotonin. We have studied
      the action of divalent cations on the enzyme activity of purified recombinant
      human GCH expressed in Escherichia coli. First, we showed that the enzyme
      activity is dependent on the concentration of Mg-free GTP. Inhibition of the
      enzyme activity by Mg2+, as well as by Mn2+, Co2+ or Zn2+, was due to the
      reduction of the availability of metal-free GTP substrate for the enzyme, when a
      divalent cation was present at a relatively high concentration with respect to
      GTP. We next examined the requirement of Zn2+ for enzyme activity by the use of a
      protein refolding assay, because the recombinant enzyme contained approximately
      one zinc atom per subunit of the decameric protein. Only when Zn2+ was present
      was the activity of the denatured enzyme effectively recovered by incubation with
      a chaperone protein. These are the first data demonstrating that GCH recognizes
      Mg-free GTP and requires Zn2+ for its catalytic activity. We suggest that the
      cellular concentration of divalent cations can modulate GCH activity, and thus
      tetrahydrobiopterin biosynthesis as well.

PMID- 14717703
TI  - Assembly of the silk fibroin elementary unit in endoplasmic reticulum and a role
      of L-chain for protection of alpha1,2-mannose residues in N-linked
      oligosaccharide chains of fibrohexamerin/P25.
AB  - Silk fibroin of Bombyx mori is secreted from the posterior silk gland (PSG) as a
      2.3-MDa elementary unit, consisting of six sets of a disulfide-linked heavy chain
      (H-chain)-light chain (L-chain) heterodimer and one molecule of fibrohexamerin
      (fhx)/P25. Fhx/P25, a glycoprotein, associates noncovalently with the H-L
      heterodimers. The elementary unit was found and purified from the endoplasmic
      reticulum (ER) extract of PSG cells. A substantial amount of fhx/P25 unassembled
      into the elementary unit was also present in ER. In normal-level fibroin
      producing breeds (J-139 and C108), the elementary unit contained fhx/P25 of
      either 30 kDa (major) or 27 kDa (minor). The 27-kDa fhx/P25 was produced from the
      30-kDa form by digestion with the bacterial alpha1,2-mannosidase in vitro. The
      elementary unit in the ER extract contained only the 30-kDa fhx/P25, whereas both
      30- and 27-kDa forms of fhx/P25 were present in the ER plus Golgi mixed extracts.
      In naked-pupa mutants [Nd(2), Nd-s and Nd-sD], extremely small amounts of fibroin
      were produced and they consisted of one molecule of 27-kDa fhx/P25 and six
      molecules of H-chain but no L-chain. When the Nd-sD mutant was subjected to
      transgenesis with the normal L-chain gene, the (H-L)6fhx1-type elementary unit
      containing the 30-kDa fhx/P25, was produced. These results suggest that fhx/P25
      in the elementary unit is largely protected from digestion with Golgi alpha1,2
      mannosidases when L-chains are present in the unit. Models suggesting a role of L
      chain for the protection of alpha1,2-mannose residues of fhx/P25 are presented.

PMID- 14717704
TI  - Mycoplasma pneumoniae HPr kinase/phosphorylase.
AB  - HPr kinase/phosphorylase (HPrK/P) is the key regulator of carbon metabolism in
      many Gram-positive bacteria. It phosphorylates/dephosphorylates the HPr protein
      of the bacterial phosphotransferase system on a regulatory serine residue in
      response to the nutrient status of the cell. In Mycoplasma pneumoniae, HPrK/P is
      one of the very few regulatory proteins encoded in the genome. The regulation of
      this enzyme by metabolites is unique among HPrK/P proteins studied so far: it is
      active as a kinase at low ATP concentrations, whereas the proteins from other
      bacteria need high ATP concentrations as an indicator of a good nutrient supply
      for kinase activity. We studied the interaction of M. pneumoniae HPrK/P with ATP,
      Fru1,6P2 and Pi by fluorescence spectroscopy. In agreement with the previously
      observed unique regulation, we found a very high affinity for ATP (K(d)=5.4
      microM) compared with the HPrK/P proteins from other bacteria. The Kd for
      Fru1,6P2 was three orders of magnitude higher, which explains why Fru1,6P2 has
      only a weak regulatory effect on M. pneumoniae HPrK/P. Mutations of two important
      regions in the active site of HPrK/P, the nucleotide binding P-loop and the
      HPrK/P family signature sequence, had different effects. P-loop region mutations
      strongly affect ATP binding and thus all enzymatic functions, whereas the
      signature sequence motif seems to be important for the catalytic mechanism rather
      than for nucleotide binding.

PMID- 14717705
TI  - Characterization of presenilin complexes from mouse and human brain using Blue
      Native gel electrophoresis reveals high expression in embryonic brain and minimal
      change in complex mobility with pathogenic presenilin mutations.
AB  - The presenilin proteins are required for intramembrane cleavage of a subset of
      type 1 membrane proteins including the Alzheimer's disease amyloid precursor
      protein. Previous studies indicate presenilin proteins form enzymatically active
      high molecular mass complexes consisting of heterodimers of N- and C-terminal
      fragments in association with nicastrin, presenilin enhancer-2 and anterior
      pharynx defective-1 proteins. Using Blue Native gel electrophoresis (BN/PAGE) we
      have studied endogenous presenilin 1 complex mass, stability and association with
      nicastrin, presenilin enhancer-2 and anterior pharynx defective-1. Solubilization
      of mouse or human brain membranes with dodecyl-d-maltoside produced a 360-kDa
      species reactive with antibodies to presenilin 1. Presenilin 1 complex levels
      were high in embryonic brain. Complex integrity was sensitive to Triton X-100 and
      SDS, but stable to reducing agent. Addition of 5 M urea caused complex
      dissolution and nicastrin to migrate as a subcomplex. Nicastrin and presenilin
      enhancer-2 were detected in the presenilin 1 complex following BN/PAGE,
      electroelution and second-dimension analysis. Anterior pharynx defective-1 was
      detected as an 18-kDa form and 9-kDa C-terminal fragment by standard SDS/PAGE of
      mouse tissues, and as a predominant 36-kDa band after presenilin 1 complex second
      dimension analysis. Membranes from brain cortex of Alzheimer's disease patients,
      or from cases with presenilin 1 missense mutations, indicated no change in
      presenilin 1 complex mobility. Higher molecular mass presenilin 1-reactive
      species were detected in brain containing presenilin 1 exon 9 deletion mutation.
      This abnormality was confirmed using cells transfected with the same presenilin
      deletion mutation.

PMID- 14717707
TI  - Endoplasmic reticulum-associated degradation of glycoproteins bearing Man5GlcNAc2
      and Man9GlcNAc2 species in the MI8-5 CHO cell line.
AB  - Endoplasmic reticulum-associated degradation of newly synthesized glycoproteins
      has been demonstrated previously using various mammalian cell lines. Depending on
      the cell type, glycoproteins bearing Man9 glycans and glycoproteins bearing Man5
      glycans can be efficiently degraded. A wide variety of variables can lead to
      defective synthesis of lipid-linked oligosaccharides and, therefore, in mammalian
      cells, species derived from Man9GlcNAc2 or Man5GlcNAc2 are often recovered on
      newly synthesized glycoproteins. The degradation of glycoproteins bearing these
      two species has not been studied. We used a Chinese hamster ovary cell line
      lacking Glc-P-Dol-dependent glucosyltransferase I to generate various proportions
      of Man5GlcNAc2 and Man9GlcNAc2 on newly synthesized glycoproteins. By studying
      the structure of the soluble oligomannosides produced by degradation of these
      glycoproteins, we demonstrated the presence of a higher proportion of soluble
      oligomannosides originating from truncated glycans, showing that glycoproteins
      bearing Man5GlcNAc2 glycans are degraded preferentially.

PMID- 14717706
TI  - Binding analyses between Human PPARgamma-LBD and ligands.
AB  - The binding characteristics of a series of PPARgamma ligands (GW9662, GI 262570,
      cis-parinaric acid, 15-deoxy-Delta(12,14)-prostaglandin J(2), LY171883,
      indomethacin, linoleic acid, palmitic acid and troglitazone) to human PPARgamma
      ligand binding domain have been investigated for the first time by using surface
      plasmon resonance biosensor technology, CD spectroscopy and molecular docking
      simulation. The surface plasmon resonance biosensor determined equilibrium
      dissociation constants (KD values) are in agreement with the results reported in
      the literature measured by other methods, indicating that the surface plasmon
      resonance biosensor can assume a direct assay method in screening new PPARgamma
      agonists or antagonists. Conformational changes of PPARgamma caused by the ligand
      binding were detected by CD determination. It is interesting that the thermal
      stability of the receptor, reflected by the increase of the transition
      temperature (T(m)), was enhanced by the binding of the ligands. The increment of
      the transition temperature (DeltaT(m)) of PPARgamma owing to ligand binding
      correlated well with the binding affinity. This finding implies that CD could
      possibly be a complementary technology with which to determine the binding
      affinities of ligands to PPARgamma. Molecular docking simulation provided
      reasonable and reliable binding models of the ligands to PPARgamma at the atomic
      level, which gave a good explanation of the structure-binding affinity
      relationship for the ligands interacting with PPARgamma. Moreover, the predicted
      binding free energies for the ligands correlated well with the binding constants
      measured by the surface plasmon resonance biosensor, indicating that the docking
      paradigm used in this study could possibly be employed in virtual screening to
      discover new PPARgamma ligands, although the docking program cannot accurately
      predict the absolute ligand-PPARgamma binding affinity.

PMID- 14717708
TI  - Differential carbohydrate epitope recognition of globotriaosyl ceramide by
      verotoxins and a monoclonal antibody.
AB  - The role of renal expression of the glycosphingolipid verotoxin receptor,
      globotriaosylceramide, in susceptibility to verotoxin-induced hemolytic uremic
      syndrome is unclear. We show that a single glycosphingolipid can discriminate
      multiple specific ligands. Antibody detection of globotriaosylceramide in renal
      sections does not necessarily predict verotoxin binding. The
      deoxyglobotriaosylceramide binding profile for verotoxin 1, verotoxin 2 and
      monoclonal anti-globotriaosylceramide are distinct. Anti-globotriaosylceramide
      had greater dependency on the intact alpha-galactose and reducing glucose of
      globotriaosylceramide than verotoxin 1, while verotoxin 2 was intermediate. These
      ligands differentially stained human kidney sections. Glomerulopathy is the
      primary verotoxin-associated pathology in hemolytic uremic syndrome. For most
      samples, verotoxin 1 immunostaining within adult glomeruli was observed (type A).
      Some samples, however, lacked glomerular binding (type B). Anti
      globotriaosylceramide (and less effectively, verotoxin 2) stained all glomeruli.
      Verotoxin 1/anti-globotriaosylceramide tubular staining was comparable. Type B
      glomerular/tubular globotriaosylceramide showed minor, but significant, fatty
      acid compositional differences. Verotoxin 1 type B glomerular binding became
      evident following pretreatment with cold acetone, or methyl-beta-cyclodextrin,
      used to deplete cholesterol. Direct visualization, using fluorescein
      isothiocyanate-verotoxin 1B, showed paediatric, but no adult glomerular staining;
      this was confirmed by anti-fluorescein isothiocyanate immunostaining. Acetone
      induced fluorescein isothiocyanate-verotoxin 1B glomerular staining in type A,
      but poorly in type B samples. Comparison of fluorescein isothiocyanate-verotoxin
      1B and native verotoxin 1B deoxyglobotriaosylceramide analogue binding showed an
      alteration in subspecificity. These studies indicate a marked heterogeneity of
      globotriaosylceramide expression within renal glomeruli and differential binding
      of verotoxin 1/verotoxin 2/anti-globotriaosylceramide to the same
      glycosphingolipid. Verotoxin 1 derivatization can induce subtle changes in
      globotriaosylceramide binding to significantly affect tissue binding.
      Heterogeneity in glomerular globotriaosylceramide expression may play a
      significant (cholesterol-dependent?) role in determining renal pathology
      following verotoxemia.

PMID- 14717709
TI  - New substrate analogues of human serotonin N-acetyltransferase produce in situ
      specific and potent inhibitors.
AB  - Melatonin is synthesized by an enzymatic pathway, in which arylalkylamine
      (serotonin) N-acetyltransferase catalyzes the rate-limiting step. A previous
      study reported the discovery of bromoacetyltryptamine (BAT), a new type of
      inhibitor of this enzyme. This compound is the precursor of a potent bifunctional
      inhibitor (analogue of the transition state), capable of interfering with both
      the substrate and the cosubstrate binding sites. This inhibitor is biosynthesized
      by the enzyme itself in the presence of free coenzyme A. In the present report,
      we describe the potency of new N-halogenoacetyl derivatives leading to a strong
      in situ inhibition of serotonin N-acetyltransferase. The new concept behind the
      mechanism of action of these precursors was studied by following the biosynthesis
      of the inhibitor from tritiated-BAT in a living cell. The fate of tritiated
      phenylethylamine (PEA), a natural substrate of the enzyme, in the presence or
      absence of [(3)H]BAT was also followed, leading to their incorporation into the
      reaction product or the inhibitor (N-acetyl[(3)H]PEA and coenzyme A
      S[(3)H]acetyltryptamine, respectively). The biosynthesis of this bifunctional
      inhibitor derived from BAT was also followed by nuclear magnetic resonance during
      its catalytic production by the pure enzyme. In a similar manner we studied the
      production of another inhibitor generated from N-[2-(7-hydroxynaphth-1
      yl)ethyl]bromoacetamide. New derivatives were also screened for their capacity to
      inhibit a purified enzyme, in addition to enzyme overexpressed in a cellular
      model. Some of these compounds proved to be extremely potent, with IC(50)s of
      approximately 30 nM. As these compounds, by definition, closely resemble the
      natural substrates of arylalkylamine N-acetyltransferase, we also show that they
      are potent ligands at the melatonin receptors. Nevertheless, these inhibitors
      form a series of pharmacological tools that could be used to understand more
      closely the inhibition of pineal melatonin production in vivo.

PMID- 14717710
TI  - Mutational and structural analysis of cobalt-containing nitrile hydratase on
      substrate and metal binding.
AB  - Mutants of a cobalt-containing nitrile hydratase (NHase, EC 4.2.1.84) from
      Pseudonocardia thermophila JCM 3095 involved in substrate binding, catalysis and
      formation of the active center were constructed, and their characteristics and
      crystal structures were investigated. As expected from the structure of the
      substrate binding pocket, the wild-type enzyme showed significantly lower K(m)
      and K(i) values for aromatic substrates and inhibitors, respectively, than
      aliphatic ones. In the crystal structure of a complex with an inhibitor (n
      butyric acid) the hydroxyl group of betaTyr68 formed hydrogen bonds with both n
      butyric acid and alphaSer112, which is located in the active center. The betaY68F
      mutant showed an elevated K(m) value and a significantly decreased k(cat) value.
      The apoenzyme, which contains no detectable cobalt atom, was prepared from
      Escherichia coli cells grown in medium without cobalt ions. It showed no
      detectable activity. A disulfide bond between alphaCys108 and alphaCys113 was
      formed in the apoenzyme structure. In the highly conserved sequence motif in the
      cysteine cluster region, two positions are exclusively conserved in cobalt
      containing or iron-containing nitrile hydratases. Two mutants (alphaT109S and
      alphaY114T) were constructed, each residue being replaced with an iron-containing
      one. The alphaT109S mutant showed similar characteristics to the wild-type
      enzyme. However, the alphaY114T mutant showed a very low cobalt content and
      catalytic activity compared with the wild-type enzyme, and oxidative
      modifications of alphaCys111 and alphaCys113 residues were not observed. The
      alphaTyr114 residue may be involved in the interaction with the nitrile hydratase
      activator protein of P. thermophila.

PMID- 14717711
TI  - Crystal structure of the chi:psi sub-assembly of the Escherichia coli DNA
      polymerase clamp-loader complex.
AB  - The chi (chi) and psi (psi) subunits of Escherichia coli DNA polymerase III form
      a heterodimer that is associated with the ATP-dependent clamp-loader machinery.
      In E. coli, the chi:psi heterodimer serves as a bridge between the clamp-loader
      complex and the single-stranded DNA-binding protein. We determined the crystal
      structure of the chi:psi heterodimer at 2.1 A resolution. Although neither chi
      (147 residues) nor psi (137 residues) bind to nucleotides, the fold of each
      protein is similar to the folds of mononucleotide-(chi) or dinucleotide-(psi)
      binding proteins, without marked similarity to the structures of the clamp-loader
      subunits. Genes encoding chi and psi proteins are found to be readily
      identifiable in several bacterial genomes and sequence alignments showed that
      residues at the chi:psi interface are highly conserved in both proteins,
      suggesting that the heterodimeric interaction is of functional significance. The
      conservation of surface-exposed residues is restricted to the interfacial region
      and to just two other regions in the chi:psi complex. One of the conserved
      regions was found to be located on chi, distal to the psi interaction region, and
      we identified this as the binding site for a C-terminal segment of the single
      stranded DNA-binding protein. The other region of sequence conservation is
      localized to an N-terminal segment of psi (26 residues) that is disordered in the
      crystal structure. We speculate that psi is linked to the clamp-loader complex by
      this flexible, but conserved, N-terminal segment, and that the chi:psi unit is
      linked to the single-stranded DNA-binding protein via the distal surface of chi.
      The base of the clamp-loader complex has an open C-shaped structure, and the
      shape of the chi:psi complex is suggestive of a loose docking within the crevice
      formed by the open faces of the delta and delta' subunits of the clamp-loader.

PMID- 14717712
TI  - Human PABP binds AU-rich RNA via RNA-binding domains 3 and 4.
AB  - Poly(A) binding protein (PABP) binds mRNA poly(A) tails and affects mRNA
      stability and translation. We show here that there is little free PABP in NIH3T3
      cells, with the vast majority complexed with RNA. We found that PABP in NIH3T3
      cytoplasmic lysates and recombinant human PABP can bind to AU-rich RNA with high
      affinity. Human PABP bound an AU-rich RNA with Kd in the nm range, which was only
      sixfold weaker than the affinity for oligo(A) RNA. Truncated PABP containing RNA
      recognition motif domains 3 and 4 retained binding to both AU-rich and oligo(A)
      RNA, whereas a truncated PABP containing RNA recognition motif domains 1 and 2
      was highly selective for oligo(A) RNA. The inducible PABP, iPABP, was found to be
      even less discriminating than PABP in RNA binding, with affinities for AU-rich
      and oligo(A) RNAs differing by only twofold. These data suggest that iPABP and
      PABP may in some situations interact with other RNA regions in addition to the
      poly(A) tail.

PMID- 14717713
TI  - Clinical applicability for the assessment of the valvular mitral stenosis
      severity with Doppler echocardiography and the proximal isovelocity surface area
      (PISA) method.
AB  - Evaluation of the severity of valvular mitral stenosis and measurements of the
      effective rheumatic mitral valve area by noninvasive echocardiography has been
      well accepted. The area is measured by the two-dimensional planimetry (PLM)
      method and the Doppler pressure half-time (PHT) method. Recently, the proximal
      isovelocity surface area (PISA) by color Doppler technique has been used as a
      quantitative measurement for valvular heart disease. However, this method needs
      more validation. The aim of this study was therefore to investigate the clinical
      applicability of the PISA method in the measurements of effective mitral valve
      area in patients with rheumatic valvular heart disease. Forty-seven patients aged
      from 23 to 71 years, with a mean age of 53 +/- 13 (25 male and 22 female, 15 with
      sinus rhythm, mean heart rate of 83 +/- 14 beats per minute, with rheumatic
      valvular mitral stenosis without hemodynamically significant mitral
      regurgitation) were included in the study. Effective mitral valve area (MVA)
      derived by the PISA method was calculated as follows: 2 x Pi x (proximal aliasing
      color zone radius)2x aliasing velocity/peak velocity across mitral orifice.
      Effective mitral valve areas measured by three different methods (PLM, PHT, and
      PISA) were compared and correlated with those calculated by the "gold standard"
      invasive Gorlin's formula. The MVA derived from PHT, PLM, PISA and Gorlin's
      formula were 1.00 +/- 0.31cm2, 0.99 +/- 0.30 cm2, 0.95 +/- 0.30 cm2 and 0.91 +/-
      0.29 cm2, respectively. The correlation coefficients (r value) between PHT, PLM,
      PISA, and Gorlin's formula, respectively, were 0.66 (P = 0.032, SEE = 0.64), 0.67
      (P = 0.25, SEE = 0.72) and 0.80 (P = 0.002, SEE = 0.53). In conclusion, the PISA
      method is useful clinically in the measurement of effective mitral valve area in
      patients with rheumatic mitral valve stenosis. The technique is relatively
      simple, highly feasible and accurate when compared with the PHT, PLM, and
      Gorlin's formula. Therefore, this method could be a promising supplement to
      methods already in use.

PMID- 14717714
TI  - The influence of ambulatory blood pressure profile on left ventricular geometry.
AB  - Besides causing a hypertrophy in the left ventricle, hypertension results in a
      change in the geometry of the left ventricle. The blood pressure, which does not
      decrease enough during the night, leads to structural changes in the left
      ventricle. In this study, the influence of 24-hour blood pressure profile on the
      left ventricular geometry was examined. Ambulatory blood pressure monitoring was
      applied to 60 patients with mild to moderate hypertension who had never been
      treated and standard echocardiographic evaluation was conducted thereafter. The
      patients were divided into two groups with respect to the ambulatory blood
      pressure profiles: the patients whose night blood pressure levels decreased by
      more than 10% compared to their daytime blood pressure levels (dipper) and those
      whose levels did not decrease that much (nondipper). The left ventricle mass
      index and the relative wall thickness of the patients were calculated. With
      respect to the left ventricle geometry, mass index and relative wall thickness of
      the patients were determined as: having normal geometry, concentric remodeling,
      eccentric hypertrophy, and concentric hypertrophy. Age, gender, systolic, and
      diastolic blood pressure were similar within the dipper and nondipper groups.
      Normal geometry, concentric remodeling, and concentric hypertrophy ratios were
      similar in both groups. Eccentric hypertrophy was higher in the nondipper group
      compared to the dipper group (42.9% vs 6.3%, P < 0.03). Patients with mild to
      moderate hypertension, whose blood pressure does not decrease enough, develop
      eccentric hypertrophy.

PMID- 14717715
TI  - Ambulatory pulse pressure, left ventricular hypertrophy and function in arterial
      hypertension.
AB  - BACKGROUND: A wide pulse pressure (PP) can provide important risk assessment
      information about myocardial infarction, carotid artery atherosclerosis, and
      global cardiovascular risk. Ambulatory pulse pressure (APP) does not have a well
      known prognostic value in hypertensive patients. METHODS: To evaluate the
      relationship among high APP, atrial volumes, and cardiac function, an
      observational study was performed on 108 untreated non-elderly hypertensive
      patients (mean age 54.23 +/- 7.12). Twenty-four-hour ambulatory blood pressure
      monitoring, Doppler and echocardiographic measurements of systolic, diastolic
      function, left and right atrial volumes, left ventricular mass index and
      dimensions, were performed in subjects with both clinic and APP > 60 mmHg (APP1
      Group). A control group of hypertensive selected subjects with both clinic and
      APP < 60 mmHg was chosen (APP 2 Group). RESULTS: The APP1 group showed left
      atrial volume enlargement, high left ventricular mass index, and impaired
      diastolic function. A positive correlation was found in the APP1 group results
      among left ventricular end diastolic diameter (r = 0.39, P < 0.01), left atrial
      volume (0.38, P < 0.05), and left ventricular mass index (r = 0.33, P < 0.05);
      clinic PP showed a statistically significant correlation with left atrial volume,
      left ventricular end diastolic diameter, and left ventricular mass index only in
      the APP1 group. CONCLUSIONS: These results suggest that elevated APP can be
      considered an effective predictor of cardiovascular risk in hypertensive
      subjects. In these patients echocardiographic evaluation of left ventricular
      function and morphology can increase the prognostic value of PP.

PMID- 14717716
TI  - Echocardiographic assessment of the right ventricular stress-velocity
      relationship under normal and chronic overload conditions.
AB  - The effects of chronic volume or pressure overload on the velocity of right
      ventricular ejection have not been previously well defined. We hypothesized that,
      as formerly shown for the left ventricle, there would be a direct relationship
      between the velocity of ejection and an estimate of systolic wall stress.
      METHODS: Echocardiograms of asymptomatic patients, not on cardiac medications,
      with either an isolated secundum atrial septal defect > or = 5 mm in diameter or
      isolated pulmonic stenosis with a peak instantaneous pressure gradient > or = 20
      mmHg, were reviewed. Forty-one patients with an atrial septal defect and 34 with
      pulmonary stenosis met criteria, and were compared to age-matched normal
      controls. Total subjects were 127 with ages ranging from 1 day to 54 years. Right
      ventricular monoplane ejection fraction, ejection time corrected for heart rate
      (ETc), mean normalized systolic ejection rate (MNSERc) and meridianal peak
      systolic wall stress (WSps) were measured. RESULTS: Compared to controls,
      ejection fractions were not significantly different, but WSps averaged 81% and
      110% higher, ETc 8% and 9% longer, and MNSERc 5% and 9% slower in the atrial
      septal defect and pulmonary stenosis groups, respectively. Among all subjects
      WSps had a significant linear correlation with ETc (r = 0.61, P < 0.01), MNSERc
      (r =-0.46, P < 0.01), and ejection fraction (r =-0.19, P < 0.05). CONCLUSIONS:
      Increases in WSps cause an incremental slowing of MNSERc in the right ventricle,
      with a relationship that is linear over a wide range of normal and abnormal
      loading conditions.

PMID- 14717717
TI  - Relative duration of transmitted mitral A wave as a measure of left ventricular
      end-diastolic pressure and stiffness.
AB  - BACKGROUND AND OBJECTIVES: The mitral A wave is transmitted to the left
      ventricular (LV) outflow tract where it is registered as Ar wave. We have related
      its transit time to the LV late diastolic stiffness. We also observed
      incidentally that the duration of the transmitted Ar wave exhibited marked
      variability and hence investigated its hemodynamic correlates. METHODS AND
      RESULTS: Mitral A wave and the Ar wave in the LV outflow tract were recorded
      using pulsed wave Doppler technique simultaneous with high fidelity LV pressure
      recordings in 20 patients undergoing cardiac catheterization. A high-speed
      contrast left ventriculogram was obtained as well. The duration of both these
      wave forms were measured and A wave duration minus the Ar wave duration was
      measured. The A minus Ar wave duration (range 0-95 ms) correlated with LV end
      diastolic pressure (r = 0.54, P = 0.014, range 4-32 mmHg), LV late diastolic
      stiffness (r = 0.62, P = 0.004, range 0.1-1.6 mmHg/ml) and the amount of LV
      pressure rise with atrial contraction (r = 0.67, P = 0.001, range 2-13 mmHg).
      CONCLUSION: A minus Ar wave duration is an easily obtainable Doppler parameter
      that is related to LV late diastolic filling pressures and stiffness and gives
      insights into aspects of LV diastolic function.

PMID- 14717718
TI  - Harmonic imaging improves sensitivity at the expense of specificity in the
      detection of patent foramen ovale.
AB  - Contrast echocardiography using agitated saline is widely employed to detect
      right to left shunt in patients with suspected patent foramen ovale (PFO). The
      sensitivity of fundamental transthoracic echocardiography (FTTE) is often limited
      by poor far-field resolution. The purpose of this study was to evaluate the test
      characteristics of harmonic imaging during transthoracic echocardiography (HTTE)
      for the detection of PFO. METHODS: Sixty-four patients referred for
      transesophageal echo (TEE) for clinical indications underwent FTTE and HTTE
      during saline contrast injections. RESULTS: TEE identified nine PFOs. For FTTE,
      the sensitivity was 78% and the specificity was 100%. For HTTE, the sensitivity
      was 100% and the specificity was 82%. All ten false positives with HTTE occurred
      after five cardiac cycles, suggesting transpulmonary transit of the bubbles.
      CONCLUSION: In the detection of PFO, HTTE improves sensitivity at the expense of
      specificity, particularly if the timing of contrast appearance in the left heart
      is ignored.

PMID- 14717720
TI  - Atypical cardiac myxomas.
AB  - Atypical cardiac myxomas are a rare occurrence and may present with a variety of
      clinical manifestations depending on the morphology and location. We present
      three cases of myxomas located atypically on the left atrial appendage ridge,
      chordae of the mitral valve, and right atrium. Echocardiography plays a prominent
      role in the diagnosis and follow-up of these patients.

PMID- 14717719
TI  - Relationship between hypercholesterolemia, lipid-lowering therapy and coronary
      flow velocity reserve evaluated by stress transesophageal echocardiography in
      patients with a negative coronary angiogram.
AB  - The coronary flow velocity reserve (CFR) depends not only on vascular,
      extravascular, and rheological factors, but also on metabolic factors, such as
      the cholesterol level. The aim of the present study was to examine the
      relationship between hypercholesterolemia, the application or not of 6 months
      lipid-lowering therapy, and the CFR evaluated by pharmacological stress
      transesophageal echocardiography (PSTEE) in patients without major coronary
      artery disease. PATIENTS AND METHODS: Sixty-nine patients with a negative
      coronary angiogram were enrolled in the study. Thirty-two of these patients
      received lipid-lowering therapy, while 37 did not. The CFR was measured by means
      of dipyridamole PSTEE in all cases, and was calculated as the ratio of
      posthyperemic to basal peak diastolic flow velocities. RESULTS: Of the 32
      patients who received lipid-lowering medication, the cholesterol level was normal
      in 16 cases (CFR 2.47 +/- 0.88), while it remained increased in 16 patients (CFR
      2.18 +/- 0.67) at the time of the examination. The 7 patients who did not
      participate in lipid-lowering therapy and who exhibited an increased cholesterol
      level were also examined (CFR 2.03 +/- 0.88). In 30 patients with normal
      cholesterol level, who did not receive any lipid-lowering medication, the CFR was
      significantly increased compared to cases with an increased level (CFR 2.65 +/-
      0.79). CONCLUSION: It may be stated that in the patients who did not receive
      lipid-lowering medication and who displayed normocholesterolemia, the CFR
      evaluated by means of PSTEE was significantly higher than in the patients who had
      an increased cholesterol level.

PMID- 14717721
TI  - Abnormal diastolic flow demonstrated by color M mode echocardiography in
      hypertrophic cardiomyopathy with mid-ventricular cavity obliteration.
AB  - We report a case of a 55-year-old woman who presented with ventricular
      tachycardia and myocardial infarction. Investigations revealed no disease of the
      epicardial coronary arteries, but a diagnosis of hypertrophic cardiomyopathy with
      mid-cavitary dynamic obstruction was made. Detailed echocardiographic
      examination, including pulse-wave Doppler and Color M Mode recordings revealed
      unusual components of diastolic dysfunction.

PMID- 14717722
TI  - Abciximab treatment for obstructive prosthetic aortic and mitral valve thrombosis
      in the presence of large thrombi, cardiogenic shock, and acute evolving embolic
      stroke.
AB  - Obstructive thrombosis of left-sided mechanical prosthetic valves is a life
      threatening complication. Intravenous thrombolytic therapy is contraindicated due
      to risk of clot embolization and surgical treatment is often required for
      hemodynamically unstable patients. We report for the first time the successful
      use of abciximab in the management of a patient in cardiogenic shock with
      multiple prosthetic valve obstructive thrombosis and evolving embolic stroke.
      Serial Doppler echocardiography and cinefluoroscopy demonstrated resolution of
      thrombi, improvements in transvalvular gradients and improvement in leaflet
      motion. This observation suggests abciximab should be considered as a therapeutic
      option in the treatment of obstructed prosthetic heart valves.

PMID- 14717723
TI  - Syncope upon swallowing caused by an esophageal hiatal hernia compressing the
      left atrium: a case report.
AB  - We describe a patient with syncope associated with swallowing. This syncope was
      caused by transient compression of the left atrium (LA) by an esophageal hiatal
      hernia. Two-dimensional echocardiography demonstrated a hyperechoic mass
      compressing the LA from the posterior. With air insufflation of the esophagus,
      compression of the LA by this hernia sac was seen to increase. Pulsed and color
      Doppler echocardiography revealed greatly decreased velocity of blood flowing
      into the LA and left ventricle (LV). Thus, marked compression of the LA by an
      esophageal hiatal hernia can cause syncope by impeding blood flow from the LA to
      the LV. Echocardiography proved highly useful in diagnosis.

PMID- 14717724
TI  - Infected cardiac myxoma.
AB  - Infected cardiac myxomas are extremely rare with only forty cases described in
      the literature. We report a case of an infected cardiac myxoma that presented in
      a manner similar to bacterial endocarditis. Our case is the first to be diagnosed
      using previously defined criteria, and is unusual in that transesophageal
      echocardiography was required to make the diagnosis.

PMID- 14717725
TI  - Unusual presentation of papillary fibroelastoma: utility of serial
      transesophageal echocardiograms.
AB  - Papillary fibroelastomas are uncommon benign tumors usually involving heart
      valves that may be potential sources of emboli. Transesophageal echocardiography
      has greatly enhanced the ability to make the diagnosis of these surgically
      treatable tumors in a timely fashion. We describe an unusual presentation of a 62
      year-old man with suspected bacterial endocarditis, in whom initial
      transesophageal echocardiogram suggested the presence of pacemaker lead infection
      but a repeat study after extraction of the pacemaker lead revealed a large
      pedunculated mass arising from the superior vena cava. The mass was surgically
      removed and histopathology revealed papillary fibroelastoma. This case is unusual
      with respect to the size and site of origin of the papillary fibroelastoma as
      well as its echocardiographic presentation mimicking vegetations on a pacemaker
      wire.

PMID- 14717726
TI  - Isolated subclavian artery aneurysm: evaluation by transesophageal
      echocardiography.
AB  - A 50-year-old man was evaluated following a motor vehicle accident. Chest X-ray
      showed a widened mediastinum. Transesophageal echocardiography was helpful in
      identifying the left subclavian artery and in demonstrating an isolated
      subclavian artery aneurysm. The TEE findings correlated well with the results of
      chest CT. Using TEE for the identification of the aortic branches in patients
      with chest trauma may be critical.

PMID- 14717727
TI  - Pectus excavatum associated with pulmonary artery dilatation.

PMID- 14717728
TI  - Echocardiographic diagnosis of a ruptured aneurysm of the sinus of Valsalva.

PMID- 14717729
TI  - Coronary artery compression caused by a large pseudoaneurysm complicating an
      acute myocardial infarction.

PMID- 14717730
TI  - Echocardiographic imaging of coronary artery abscess following stent
      implantation.

PMID- 14717732
TI  - The Chiari network in an echocardiography student.

PMID- 14717733
TI  - Three-dimensional transesophageal echocardiographic delineation of ventricular
      septal aneurysm producing right ventricular outflow obstruction in an adult.
AB  - We report three-dimensional echocardiographic delineation of a congenital
      aneurysm of the membranous interventricular septum causing right ventricular
      outflow tract obstruction in an adult patient. To our knowledge, these findings
      have not been described before.

PMID- 14717734
TI  - Mitral prosthetic inflow mimicking severe aortic regurgitation.
AB  - We describe two patients in whom mitral valve prosthetic inflow mimicked severe
      aortic regurgitation. Repeat transthoracic echocardiography using multiple
      transducer angulations and a narrow color Doppler sector angle in one patient and
      a color Doppler M-Mode study in the second patient proved useful in excluding the
      presence of severe aortic regurgitation.

PMID- 14717742
TI  - A refined technique for determining the respiratory gas exchange responses to
      anaerobic metabolism during progressive exercise - repeatability in a group of
      healthy men.
AB  - The respiratory gas exchange and ventilation during an incremental cycle exercise
      test were analysed in a group of 19 healthy, moderately fit men. Different
      computer algorithms were used to estimate the VO2 values where: (i) the rate of
      VCO(2) increase just exceeds the rate of VO(2) increase (DX, derivative
      crossing), (ii) VCO(2)/VO(2) = 1.00 (PX, point of crossing) and (iii) ventilation
      (VE) increases disproportionately in relation to VCO(2) (PQ, point of VCO(2)
      equivalent rise). The DX and PQ measurements were analysed using a new approach
      employing polynomial regression and the value of PX was determined following low
      pass filtration of raw data. The repeatability of the measurements was evaluated
      with a 5-6 week interval between the tests. The correlations between tests were
      0.75 at DX, 0.85 at PX and 0.62 at PQ. The mean differences between the repeated
      tests were not statistically significant. The repeatability of VO2, in absolute
      values expressed as +/-2 SD of the differences between the tests, had values of
      5.0, 6.1 and 9.5 ml min(-1) kg(-1) for DX, PX and PQ, respectively. The mean
      value of VO(2) for each measurement point expressed as a percentage of VO(2 max)
      was 54% at DX, 68% at PX and 70% at PQ. The most common sequence of the measured
      values was DX < PX < PQ, but the sequence DX < PQ < PX was also observed. It is
      concluded that the gas exchange responses to developing anaerobic metabolism
      during progressive exercise can be characterized by a series of thresholds.
      However, the considerable variation in absolute values in the two testing
      occasions requires further attention.

PMID- 14717743
TI  - Decrease in heart rate variability with overtraining: assessment by the Poincare
      plot analysis.
AB  - Numerous symptoms have been associated with the overtraining syndrome (OT),
      including changes in autonomic function. Heart rate variability (HRV) provides
      non-invasive data about the autonomic regulation of heart rate in real-life
      conditions. The aims of the study were to: (i) characterize the HRV profile of
      seven athletes (OA) diagnosed as suffering of OT, compared with eight healthy
      sedentary (C) and eight trained (T) subjects during supine rest and 60 degrees
      upright, and (ii) compare the traditional time- and frequency-domain analysis
      assessment of HRV with the non-linear Poincare plot analysis. In the latter each
      R-R interval is plotted as a function of the previous one, and the standard
      deviations of the instantaneous (SD1) and long-term R-R interval variability are
      calculated. Total power was higher in T than in C and OA both in supine (1158 +/-
      1137, 6092 +/- 3554 and 2970 +/- 2947 ms2 for C, T and OA, respectively) and in
      upright (640 +/- 499, 1814 +/- 806 and 1092 +/- 712 ms2 for C, T and OA,
      respectively; P<0.05) positions. In supine position, indicators of
      parasympathetic activity to the sinus node were higher in T compared with C and
      OA (high-frequency power: 419.1 +/- 381.2, 1105.3 +/- 781.4 and 463.7 +/- 715.8
      ms2 for C, T and OA, respectively; P<0.05; SD1: 29.5 +/- 18.5, 75.2 +/- 17.2 and
      37.6 +/- 27.5 for C, T and OA, respectively; P<0.05). OA had a marked
      predominance of sympathetic activity regardless of the position (LF/HF were 0.47
      +/- 0.35, 0.47 +/- 0.50 and 3.96 +/- 5.71 in supine position for C, T and OA,
      respectively, and 2.09 +/- 2.17, 7.22 +/- 6.82 and 12.04 +/- 10.36 in upright
      position for C, T and OA, respectively). The changes in HRV indexes induced by
      the upright posture were greater in T than in OA. The shape of the Poincare plots
      allowed the distinction between the three groups, with wide and narrow shapes in
      T and OA, respectively, compared with C. As Poincare plot parameters are easy to
      compute and associated with the 'width' of the scatter gram, they corroborate the
      traditional time- and frequency-domain analysis. We suggest that they could be
      used to indicate fatigue and/or prevent OT.

PMID- 14717744
TI  - Electrophysiology of inducible atrial flutter in patients with atrioventricular
      nodal reentrant tachycardia.
AB  - An association between atrial flutter and atrioventricular nodal reentrant
      tachycardia (AVNRT) has been observed, but the underlying mechanisms are poorly
      defined. This issue was therefore investigated by comparing the
      electrophysiological properties of AVNRT patients with and without inducible
      atrial flutter and those of patients with a history of flutter. Twenty-nine
      patients with clinically documented atrial flutter and 104 with AVNRT were
      studied. Atrial flutter was induced in 38 (37%) AVNRT patients during
      standardized electrophysiological testing before radiofrequency ablation. The
      atrial relative refractory periods in AVNRT patients with inducible flutter (260
      +/- 30 ms) were significantly shorter than those of either patients with a
      history of flutter (282 +/- 30 ms; P = 0.02) or AVNRT patients without inducible
      flutter (284 +/- 38 ms; P = 0.006). The atrial effective refractory periods in
      AVNRT patients with inducible flutter (205 +/- 31 ms) were shorter than in AVNRT
      patients without inducible flutter (227 +/- 40 ms; P = 0.01). The maximum AH
      interval during premature atrial stimulation in patients with clinical flutter
      (239 +/- 94 ms) was shorter than in AVNRT patients either with (290 +/- 91 ms; P
      = 0.04) or without inducible flutter (313 +/- 101 ms; P = 0.002). However, no
      significant differences were found in the maximum AH interval achieved during
      incremental atrial pacing among different groups. Our data show that a non
      clinical flutter could more often be induced in those who had short atrial
      refractoriness. Despite their anatomical proximity, the slow pathway conduction
      of AVNRT and the isthmus slow conduction of flutter may be related to different
      mechanisms.

PMID- 14717745
TI  - Electromyographic signs of neuromuscular fatigue are concomitant with further
      increase in ventilation during static handgrip.
AB  - We questioned if a non-linear increase in ventilation defining a ventilatory
      threshold (V(Th)) accompanied the electromyographic (EMG) signs of neuromuscular
      fatigue. Indeed, the intramuscular accumulation of metabolites may activate the
      afferent nervous pathways responsible for both the 'muscle wisdom' phenomenon and
      the respiratory centre activation. During inframaximal (50%) handgrip sustained
      until exhaustion, minute ventilation (V(E)), V(E)/V(O2) and V(E)/V(CO2) ratios
      were measured simultaneously with surface EMG of the 'flexor digitorum' muscle.
      V(Th) was defined as a non-linear V(E) increase and/or an abrupt V(E)/V(O2)
      increase without any concomitant increase in the V(E)/V(CO2) ratio. Handgrip was
      repeated during complete arterial blood flow interruption in order to suppress
      any venous return from the exercising forearm. In both control and blood flow
      interruption conditions, an abrupt increase in the V(E)/V(O2) ratio was measured
      in the majority of trials (13 of 15 and 14 of 15, respectively) and the EMG signs
      of neuromuscular fatigue (a decline in median frequency and/or a non-linear
      increase in low-frequency EMG energies, E(L)) were concomitant with the V(Th)
      determination. Thus, V(Th) occurs during sustained static contraction and is
      concomitant with EMG signs of neuromuscular fatigue. Neurogenic factors seem to
      be responsible for the two responses which persist despite the absence of any
      release of metabolites in the circulation.

PMID- 14717746
TI  - Assessment of 99mTc-sestamibi myocardial redistribution following acute
      myocardial infarction and revascularization.
AB  - Revascularization with primary percutaneous coronary intervention for ST segment
      elevation myocardial infarction results in restored epicardial flow in the
      majority of patients. However, in more than 25% of patients, flow does not
      translate into tissue perfusion. To assess revascularization success, it is
      necessary to evaluate beyond epicardial flow and to address tissue perfusion.
      99mTc-sestamibi single photon emission computed tomography (SPECT) might be
      useful in this setting, but whether sestamibi redistributes when administered
      during reperfusion has been debated. The aim of this study was to investigate
      whether clinically significant redistribution could be detected in a porcine
      model mimicking acute myocardial infarction and revascularization. Ten pigs were
      studied in a closed-chest model of myocardial infarction. 99mTc-sestamibi was
      administered during reperfusion, and SPECT was performed every 30 min for 4 h.
      The quantitative program CEQUAL was used for analysis and perfusion defects were
      reported in percentage. All animals had eight acquisitions. The size of the
      perfusion defect in the individual animals ranged from (mean +/- SD) 13 +/- 3 to
      34 +/- 2%. The difference between the first and the last perfusion defect in a
      single animal was (mean +/- SD) 2.5 +/- 5.3%, which is not statistically
      significant (P = 0.17). The slopes of regression lines obtained from plots of the
      individual values ranged from -1.39 to 0.76 with a mean of -0.23 +/- 0.68, which
      is not statistically significant (P = 0.31). In conclusion, we found no sign of
      sestamibi redistribution in this experimental set-up of reperfused myocardial
      infarction. If these findings can be extrapolated to clinical practice, then it
      means that acquisition can be performed at any time within the first 4 h after
      tracer injection without significant difference in perfusion assessment.

PMID- 14717747
TI  - Peripheral pulse pressure responses to postural stress do not reflect those at
      the carotid artery.
AB  - OBJECTIVE: Interpretation of baroreflex cardiovascular control requires accurate
      assessment of pulse pressure (PP) in central arteries under conditions of varying
      systemic or hydrostatic pressure. The objective of this study was to examine
      whether changes in PP during postural stress were similar in the peripheral
      versus carotid arteries. DESIGN: Protocol A: Pulse pressure was measured in both
      the left (Millar tonometer) and right (Colin Pilot) radial arteries, and in the
      finger (Finapres) in seated subjects (n = 7) who performed Valsalva's manoeuvre.
      Protocol B: PP was measured from the carotid (Millar tonometer), and from the
      finger and wrist kept at the level of the carotid artery, during supine and 60
      degrees head-up postures. RESULTS: Protocol A: Pulse pressures during Valsalva's
      manoeuvre were highly correlated between all devices (r = 0.6-0.8). Protocol B:
      compared with supine, PP was reduced in both the finger and wrist during head-up
      tilt (HUT) (P<0.05), but not in the carotid artery. CONCLUSIONS: During Valsalva
      manoeuvers the Millar and Colin tonometers similarly tracked PP over a wide range
      of rapidly changing pressures. This observation provided confidence for the
      further use of the hand-held device for central measurements during changes in
      posture. The results from Protocol B indicate that peripheral PP measurements are
      not suitable surrogates for carotid pulse pressures during HUT.

PMID- 14717748
TI  - Estimate of pulmonary diffusing capacity for oxygen during exercise in humans
      from routine O(2) and CO(2) measurements.
AB  - A method to estimate pulmonary diffusing capacity for O(2) (D(LO2)) during
      exercise based on routine O(2) and CO(2) transport variables is presented. It is
      based on the fitting of a mathematical model to gas exchange data. The model
      includes heterogeneity (described as two exchanging compartments), diffusion
      limitation and right-to-left shunt. Mass conservation equations and Bohr
      integration were solved to calculate partial pressures in each compartment.
      Diffusion was distributed with perfusion. Two-compartment ventilation and
      perfusion distributions were estimated at rest during conditions of negligible
      diffusion limitation. These distributions were used during hypoxic and normoxic
      exercise to obtain the D(LO2) from the model computations (D(LO2)2C) compatible
      with experimental data. Three normals, four sarcoid patients and four patients
      after lung resection were studied. An independent technique for carbon monoxide
      was used to provide experimental estimates of DLo2 (D(LO2)EXP, rebreathing
      technique for sarcoid patients and single breath for lung resection). D(LO2)2C
      was highly correlated with D(LO2)EXP (r2 = 0.95, P<0.001) and the slope of the
      regression line was not statistically different from 1. The mean (D(LO2)EXP -
      D(LO2)2C) difference was -1.0 +/- 7.4 ml min-1 mmHg-1. The results suggest that
      use of a refined analytical procedure allows for assessment of D(LO2) from
      routine O(2) and CO(2) measurements comparable with those obtained from
      independent carbon monoxide techniques. The method may be an alternative for
      estimates of D(LO2) during exercise.

PMID- 14717749
TI  - Regional ventilation and distribution of emphysema - a quantitative comparison.
AB  - The distribution of ventilation and emphysema throughout the lung was compared in
      20 emphysematous patients who were candidates for lung volume reduction surgery.
      Ventilation distribution among 1.6-cm-high stripe regions was obtained in supine
      position by planar gamma camera scintigraphy after inhalation of technegas.
      Results from nine healthy subjects provided normal stripe count rates. Patient
      count rates were expressed as the difference from predicted normal stripe count
      rate (DeltaSVI). Thus, DeltaSVI is a relative index of abnormal ventilation.
      Emphysema was assessed quantitatively by a density mask method on corresponding
      slices of high resolution computed tomography (HRCT). The results show that in
      the majority of patients, there is a highly significant relationship between the
      degree of stripe hypoventilation and the amount of distribution of emphysema, but
      in some patients no such relationship is found. We speculate that the
      distribution of airway obstruction not necessarily follows the distribution of
      emphysema, which could explain the lack of concordance between ventilation and
      emphysema distribution in some patients. We conclude that ventilation
      scintigraphy contains complementary information to lung HRCT.

PMID- 14717750
TI  - Neonatal ACE inhibition in rats interferes with lung development.
AB  - The renin-angiotensin system (RAS) is developmentally up-regulated and it is
      essential for kidney development in several species. Given the fact that the rat
      lung undergoes postnatal development, the mammalian lung possesses the highest
      angiotensin-converting enzyme (ACE) levels and ACE activity increases during the
      first weeks postpartum, we tested the hypothesis that ACE inhibition influences
      postnatal lung development. Rats were given the ACE inhibitor enalapril (10 mg
      kg(-1)) from 0 to 9 days of age and their lungs were examined at day 4 and 9.
      Lung structure was evaluated by means of light microscopy, and surface tension of
      bronchoalveolar lavage fluid was measured by means of a Wilhelmy balance.
      Neonatal ACE inhibition lowered the surface tension of bronchoalveolar lavage
      fluid and caused widening of respiratory airspaces and thinning of alveolar
      septa. Our results suggest that early postnatal ACE inhibition in rats interferes
      with lung development.

PMID- 14717752
TI  - Treatment of breast cancer in medically underserved women: a review.
AB  - Women at risk of being undertreated for breast cancer include women who are
      older, from minority groups, from lower socioeconomic backgrounds, and those
      without health insurance or insured by Medicaid. Recent reviews of the cancer
      care experience of medically underserved populations indicate that breast cancer
      care may be even less optimal for these populations than the majority of women.
      These are the same women who may experience difficulty obtaining access to
      medical care once they are diagnosed with breast cancer. Indirect proof of
      problems with access is manifested as higher recurrence rates of breast cancer
      and differences in breast cancer-specific survival among medically underserved
      women. Multiple factors have been shown to affect access to medical care, and
      therefore quality of care, including patient-level factors, provider-level
      factors, and health system factors. This article reviews the current state of
      these factors in explaining breast cancer care in medically underserved women.

PMID- 14717753
TI  - Breast cancer evaluation: medical legal issues.
AB  - Delay in diagnosis of breast cancer is the leading cause for malpractice lawsuits
      against physicians. Most cases are tried under civil law and, more specifically,
      the tort of negligence which defines departures from conduct of a reasonable and
      prudent physician under similar circumstances. The role of both the clinician and
      imager, separately and in concert, needs to be understood with respect to
      accomplishing early diagnosis and avoiding potential legal exposure. An
      understanding of basic legal concepts as they apply to medical practice should
      provide health care providers a perspective from which to apply their skills and
      avoid unnecessary legal exposure.

PMID- 14717754
TI  - Improving the timeliness of written patient notification of mammography results
      by mammography centers.
AB  - Timely reporting of mammogram results helps to reduce anxiety for women with
      negative results and speeds up diagnosis or treatment in the case of abnormal
      results. The goal of this project was to improve the rate at which Virginia
      mammography centers provide a written report to women in lay terms within 30 days
      of a mammogram. The project included six intervention and five control
      mammography centers. The baseline period was prior to when new regulations in the
      Mammography Quality Standards Act (MQSA) took effect in April 1999. The re
      measurement period was after April 1999. Data were obtained from abstraction of
      mammography reports and patient notification letters from a sample of patients
      with negative and abnormal mammography results at each mammography center. Each
      intervention mammography center received a notebook that included numerous tools
      on systems for patient notification and tracking, baseline notification rates and
      other abstracted information, biopsy recommendations, sample results letters, and
      a copy of the MQSA. For negative mammograms, the intervention group in aggregate
      increased from 24% at baseline to 79% at re-measurement in their rate of
      notification within 30 days. The control group increased from 25% to 46%. For
      abnormal mammograms, increases were from 35% to 85% and from 25% to 58%,
      respectively. The intervention group's increases were considerably higher,
      suggesting an effect due to the interventions that involved technical assistance,
      education, and system change. All increases were statistically significant (p <
      0.01). At baseline, three intervention centers and two controls had policies for
      written notification. All 11 had policies at re-measurement. However, only two of
      the five control centers could provide clear supporting documentation for dates
      of notification at re-measurement. Mammography centers can benefit from guidance
      in the form of intervention materials specifically designed to address the MQSA
      sections that apply to patient notification, tracking, and positive predictive
      value of biopsy recommendations.

PMID- 14717755
TI  - Significance of mismatch repair protein expression in the chemotherapeutic
      response of sporadic invasive ductal carcinoma of the breast.
AB  - The mismatch repair (MMR) gene plays a key role in the correction of DNA damage,
      and the loss of MMR has been implicated in resistance to a variety of
      chemotherapeutic drugs. The purpose of this study was to assess whether the
      reduced expression of hMLH1 and/or hMSH2 affects the chemotherapeutic
      responsiveness of sporadic invasive ductal carcinoma of the breast.
      Immunohistochemical studies were performed on 71 histologic specimens of breast
      cancer taken from the patients treated with surgery and subsequent
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide,
      Adriamycin, and 5-fluorouracil (CAF) chemotherapy for stage II or III primary
      breast cancer. Single-strand conformational polymorphism polymerase chain
      reaction (PCR-SSCP) and sequencing were carried out in 16 patients. A combined
      immunoreactivity score (hMLH1-IS and hMSH2-IS) was calculated by multiplying the
      staining grade by the intensity score. Positive expression (>4) of hMLH1-IS and
      hMSH2-IS were 57.7% and 60.6%, respectively, and complete losses of hMLH1 and
      hMSH2 were observed in 4.2% of patients. Of the patients with advanced cancer
      with lymph node metastasis, those having a low hMLH1-IS had a significantly
      higher failure rate with the CMF regimen than those having a high hMLH1-IS (p =
      0.03). No significant difference was noted in chemotherapeutic response according
      to hMLH1 and hMSH2 expression in the CAF group. Both hMLH1-IS (p = 0.03) and
      progesterone receptor (PR) status (p = 0.03) were well correlated with CMF
      chemotherapy response in breast cancers with lymph node metastasis. Our study
      shows that a lack of hMLH1 expression may play a role in drug resistance,
      especially in the CMF group, and immunohistochemical assay for MMR protein can be
      used as a convenient tool for evaluating chemotherapeutic response in patients
      with breast cancer.

PMID- 14717756
TI  - Effect of tamoxifen on breast tissue density in premenopausal breast cancer.
AB  - It has been established that hormone replacement therapy (HRT) increases breast
      tissue density on mammography in up to 30% of women receiving treatment. The
      effects of selective estrogen receptor modulators (SERMs) on breast tissue have
      received limited attention, although there have been several reports of tamoxifen
      decreasing mammographic tissue density in some women undergoing adjuvant or
      prophylactic breast cancer treatment. We report a case of a premenopausal woman
      treated with tamoxifen for 5 years whose mammographic density decreased while on
      tamoxifen and returned to her baseline density following termination of the drug.
      A regression of breast tissue may be reflective of sensitivity to tamoxifen and
      possibly, indicative of therapeutic benefit associated with treatment.
      Furthermore, induction of a more radiolucent pattern by tamoxifen may
      independently benefit women by enhancing mammographic detection. The clinical
      significance of resumption of a dense breast pattern following discontinuation of
      tamoxifen remains to be determined.

PMID- 14717757
TI  - Value of Three-Dimensional Helical CT Image-Guided Planning for Made-to-Order
      Lumpectomy in Breast Cancer Patients.
AB  - The authors reviewed Niigata Cancer Center Hospital's experience treating
      patients with lumpectomy to evaluate the utility of three-dimensional helical
      computed tomography (3D-CT) image-guided made-to-order lumpectomy and determine a
      positive margin rate. From April 1993 to September 2000, 251 breasts in 248
      patients were treated with lumpectomy with a 1 cm macroscopic free margin. In 213
      breasts (85%), 3D-CT image-guided made-to-order lumpectomy was performed. Thirty
      eight breasts (15%) underwent a lumpectomy without 3D-CT. The lumpectomy specimen
      was sectioned at 5 mm intervals. Margin status was classified as negative (no
      invasive or ductal carcinoma in situ (DCIS) within 2 mm from the cut surface) or
      positive. Positive margins were classified as focally positive (invasive or DCIS
      transected at the margin within 5 mm or one slide) or massively positive. With 3D
      CT image-guided lumpectomy, 21% (45/213) of lesions had a positive margin and 42%
      (16/38) of lesions without 3D-CT image-guided lumpectomy had a positive margin (p
      = 0.0055). For lesions with massively positive margins, the rates were 9% (4/45)
      for 3D-CT image-guided lumpectomy and 38% (6/16) for lumpectomy without 3D-CT (p
      = 0.0152). 3D-CT image-guided made-to-order lumpectomy decreased the positive
      surgical margin rate. Among patients with positive margins, those with 3D-CT
      image-guided lumpectomy have less residual cancer than those without 3D-CT.

PMID- 14717758
TI  - Increased use of adjuvant regional radiotherapy for node-positive breast cancer
      in British Columbia.
AB  - This study was to determine if the use of regional radiotherapy (RT) changed in
      British Columbia after publication of new randomized trial data in 1997. Women
      with pathologic T1-3N1, nonmetastatic breast cancer treated with a mastectomy or
      breast-conserving surgery (BCS) were included. The use of regional RT was
      compared in two cohorts: cohort 1, July 1, 1995-June 30, 1997 (n = 834); and
      cohort 2, July 1, 1998-June 30, 2000 (n = 1072). All p-values were two-sided.
      Adjuvant systemic therapy was given to 96% and 95% of women in cohorts 1 and 2,
      respectively. Forty-five percent of cohort 1 and 48% of cohort 2 had BCS.
      Regional RT was received by 44% of cohort 1 and 66% of cohort 2 (p < 0.001).
      Eighty-eight percent and 90% of women with four or more positive nodes in cohorts
      1 and 2 received regional RT, respectively. For women in cohorts 1 and 2 with one
      to three positive nodes, regional RT use increased from 32% to 54% after
      mastectomy, and from 23% to 59% after BCS, respectively (p < 0.001 for both).
      Publication of randomized trials and a coordinated guideline implementation
      process in British Columbia was associated with a significant increase in the use
      of regional RT in women with one to three positive nodes.

PMID- 14717759
TI  - An unusual presentation of neurofibromatosis of the breast.
AB  - Patients with neurofibromatosis type I or von Recklinghausen disease develop
      neurofibromas in the subcutaneous tissues, including the breast. There are two
      German reports of massive neurofibromatosis of the breast, but few reports of
      massive neurofibromatosis of the breast in the English literature. We present an
      unusual case of neurofibromatosis of the breast with large neurofibromas
      predominantly noted protruding from both nipple-areolar complexes.

PMID- 14717760
TI  - Granulocytic sarcoma (chloroma) of the breast: a diagnostic dilemma and review of
      the literature.
AB  - Primary granulocytic sarcoma (GS) is a rare entity, and even more unusual is the
      presence of primary GS of the breast. We describe such a case and report on the
      19 cases of primary breast GS in the literature. Primary GS presents most
      commonly in skin and lymph nodes, therefore when it presents in the breast,
      misdiagnosis is a common problem. Primary breast GS is misdiagnosed most
      frequently as lymphoma or sarcoma. Histologic testing and immunostains are
      essential to provide the proper diagnosis. It appears that early initiation of
      systemic acute myelogenous leukemia (AML)-type chemotherapy is beneficial and may
      delay or avert the development of AML in bone marrow and blood.

PMID- 14717761
TI  - Dramatic response of choroidal metastases from breast cancer to a combination of
      trastuzumab and vinorelbine.
AB  - We report the case of a 57-year-old woman with unilateral choroidal metastases
      from HER-2-positive breast cancer. She was given trastuzumab and vinorelbine with
      complete resolution of her visual defect after one cycle of treatment. This
      article illustrates that treatment using trastuzumab-containing chemotherapy
      regimens in HER-2-overexpressing breast cancer patients with choroidal metastases
      may be an alternative therapeutic strategy to initial orbital irradiation.

PMID- 14717762
TI  - Epidermal inclusion cyst of the breast: clinical, radiologic, and pathologic
      correlation.

PMID- 14717763
TI  - Lobular Neoplasia within a Myoid Hamartoma of the Breast.

PMID- 14717764
TI  - Atypical mycobacterium breast infection.

PMID- 14717765
TI  - Blood dissemination of mammaglobin-specific RNA during core needle biopsy in
      patients with invasive breast carcinoma.

PMID- 14717766
TI  - Synchronous presentation of breast cancer and pheochromocytoma in a 57-year-old
      woman.

PMID- 14717767
TI  - Suspicious nipple discharge and breast magnetic resonance imaging.

PMID- 14717770
TI  - Fungal endophthalmitis in acute leukaemia.

PMID- 14717771
TI  - Successful intra-articular chemotherapy for relapsed acute myeloid leukaemia
      infiltrating the knee joint.

PMID- 14717772
TI  - Neonatal screening for sickle cell disorders.

PMID- 14717773
TI  - Genetic insights into the clinical diversity of beta thalassaemia.

PMID- 14717774
TI  - Additional cytogenetic abnormalities in adults with Philadelphia chromosome
      positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group
      B.
AB  - We analysed the nature and prognostic significance of secondary cytogenetic
      changes in 111 newly diagnosed adults with acute lymphoblastic leukaemia (ALL)
      and t(9;22)(q34;q11.2) or its variants. Secondary aberrations were seen in 75
      (68%) patients. They included, in order of descending frequency: +der(22)t(9;22),
      +21, abnormalities of 9p, high hyperdiploidy (>50 chromosomes), +8, -7, +X and
      abnormalities resulting in loss of material from 8p, gain of 8q, gain of 1q and
      loss of 7p. Eighty patients (72%) had > or =1 normal metaphase in their
      karyotype. There were four balanced and 12 unbalanced translocations previously
      unreported in ALL with t(9;22). The t(2;7)(p11;p13) and
      der(18)t(8;18)(q11.2;p11.2) were seen in two cases each, and have never before
      been reported in haematological malignancy. All but four patients were treated on
      front-line Cancer and Leukaemia Group B clinical protocols. The presence of -7 as
      a sole secondary abnormality was associated with a lower complete remission (CR)
      rate (P = 0.004), while the presence of > or =3 aberrations was associated with a
      higher CR rate (P = 0.009) and +der(22)t(9;22) with a higher cumulative incidence
      of relapse (P = 0.02). It will be of interest to see if newly diagnosed t(9;22)
      positive adult ALL patients with these and other secondary aberrations respond
      differently to treatment regimens that include imatinib mesylate.

PMID- 14717775
TI  - Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22-23
      deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical
      Cancer Research.
AB  - Mantle cell lymphoma (MCL) shares immunophenotypic and karyotypic features with
      chronic lymphocytic leukaemia. The latter comprises two distinct entities with
      prognosis dependent upon immunoglobulin heavy chain (IgH) gene mutational status
      and the presence of 11q deletion. We evaluated the relevance of IgH gene
      mutational status, IgV gene family usage and presence of 11q deletion in a series
      of 42 histologically reviewed classical MCL cases to determine the prognostic
      impact. VH3 was the most common VH family, with VH3-21 being the most frequent
      individual VH gene. Approximately 30% of the cases had a IgH somatic mutation
      rate higher than 2%, but was only higher than 4% in <10% of cases. Half of the
      cases had deletion of chromosome 11q21-telomere (11q21->ter), with two minimal
      deleted regions, at 11q22.2 and 11q23.2. There was no association between 11q
      loss and IgH gene somatic mutation rate; the use of VH3-21 gene could be
      associated with a better prognosis.

PMID- 14717776
TI  - CD27-triggering on primary plasma cell leukaemia cells has anti-apoptotic effects
      involving mitogen activated protein kinases.
AB  - Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is
      related to multiple myeloma (MM) and is characterized by a poor prognosis. In a
      previous study we demonstrated that PCL plasma cells display a high expression of
      CD27, in contrast to MM plasma cells. The present study was set out to assess the
      functional properties of CD27 expressed on PCL plasma cells by triggering with
      its ligand CD70. Using CD27-expressing purified plasma cells from a PCL patient
      we demonstrated that CD27-triggering modestly inhibited spontaneous and
      dexamethasone-induced apoptosis. In vitro stimulation and Western blotting showed
      that activation of p38 and extracellular-regulated kinase 1/2 (ERK1/2) mitogen
      activated protein kinases (MAPK) was associated with CD27-mediated signal
      transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti
      apoptotic effects of CD27-triggering. Interestingly, simultaneous inhibition of
      p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone-induced apoptosis.
      Finally, in dexamethasone-treated PCL cells, CD27-triggering was associated with
      persistent DNA-binding activity of activator protein 1 (AP-1) but not of nuclear
      factor-kappaB. These findings suggest that, in primary PCL, specific anti
      apoptotic pathways exist that might provide novel therapeutic targets.

PMID- 14717777
TI  - Systemic AL amyloidosis due to non-Hodgkin's lymphoma: an unusual
      clinicopathologic association.
AB  - Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar
      deposits, leading to organ dysfunction and death. Rarely, AL has been associated
      with non-Hodgkin's lymphoma (NHL), although this association has not been well
      characterized. We report a series of six patients with AL associated with NHL,
      primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with
      frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac
      involvement. Positron emission tomography scans were negative. Bone marrow and
      lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma
      cells. Serum free light chains were elevated, and correlated with response to
      therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was
      typical for AL, reflecting previously observed correlations between germline gene
      use and organ tropism. Five patients received rituximab-based therapies with two
      responses. Two patients underwent autologous stem cell transplantation with one
      complete haematological response. Four patients survive at 10-132 months from
      diagnosis. AL with NHL has distinctive clinical features but employs the same Ig
      VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free
      light chain levels are useful for tracking response to therapy. Treatments aimed
      at both lymphoid and plasma cell components appear warranted.

PMID- 14717778
TI  - Signalling molecules and cytokine production in T cells of multiple myeloma
      increased abnormalities with advancing stage.
AB  - T-cell immune dysfunction in patients with malignant tumours has been attributed
      to the altered expression of components of the T-cell receptor (TCR)/CD3 complex
      and their associated intracellular protein tyrosine kinases. In this study, four
      colour flow cytometry was applied to study the surface bound molecules
      TCRalphabeta, CD28, CD152 and CD154 involved in T-cell signalling and the signal
      transduction molecules CD3zeta, p56lck, p59fyn, ZAP-70 and phosphatidyl-inositol
      3 kinase (PI3-k) as well as the intracellular cytokines interferon-gamma (IFN
      gamma), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated
      and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of
      multiple myeloma (MM) patients at different stages of the disease. Multiple
      abnormalities were demonstrated in the CD4 and CD8 populations, both under non
      stimulated and superantigen-stimulated conditions. There was a marked reduction,
      particular in advanced stage MM, in the proportion of CD4 and CD8 cells
      expressing CD28, CD152, CD3zeta, p56lck, ZAP-70 and PI3-k. The level of
      intracellular T-cell cytokines (IFN-gamma, IL-2 and IL-4) was normal or increased
      in non-stimulated cells but activation-induced cytokine production was impaired.
      These results illustrated profound and multiple T-cell signalling defects, from
      the surface and down-stream, consistent with involvement of a master T-cell
      function, especially in advanced stage MM. These data should be taken into
      consideration when developing immune-based therapeutic approaches and when
      applying new emerging technologies that aim to restore T-cell functions.

PMID- 14717779
TI  - Reliable detection of clonal IgH/Bcl2 MBR rearrangement in follicular lymphoma:
      methodology and clinical significance.
AB  - The prognostic significance of IgH/Bcl2 rearrangement in follicular lymphoma (FL)
      remains contentious; polymerase chain reaction (PCR) methodology and tissue
      source variability may account for some inconsistencies. As IgH/Bcl2 major
      breakpoint region (MBR) sequences may be found in normal blood, an MBR+ result by
      conventional PCR in blood/bone marrow may not indicate FL. To establish tumour
      MBR status, 190 lymphoid tissue samples with histologically evident FL (and
      therefore >1% tumour cells) were examined by real-time quantifiable PCR; 50%
      (95/190) had clonal MBR IgH/Bcl2 (MBR was considered clonal when >1%). Overall
      survival (median = 11.5 years) of MBR+ and MBR- patients was not significantly
      different.

PMID- 14717780
TI  - Increased CD11b neutrophil expression in Budd-Chiari syndrome or portal vein
      thrombosis secondary to polycythaemia vera.
AB  - Budd-Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently
      associated with polycythaemia vera (PV). In an attempt to elucidate the
      mechanisms of BCS/PVT secondary to PV (T-PV), CD11b neutrophil expression,
      neutrophil oxidative burst and platelet-neutrophil complexes (PNC) were assessed
      in 17 such patients. Three groups served as controls: BCS/PVT not secondary to PV
      (T-nPV; n = 20), PV without thrombosis (PV-nT; n = 16), and healthy controls (HC;
      n = 20). Baseline CD11b expression (in mean fluorescence intensity units) was 101
      [95% confidence interval (CI): 79-128] in T-PV patients, versus 25 (95% CI: 18
      35) in T-nPV, 59 (95% CI: 43-80) in PV-nT, and 34 (95% CI: 25-48) in HC (P <
      0.001). After N-formyl-L-methionyl-L-leucyl-L-phenylalanine activation, T-PV
      patients also showed higher CD11b values: 190 (95% CI: 151-238), versus 55 (95%
      CI: 41-72) in T-nPV, 111 (95% CI: 81-153) in PV-nT, and 77 (95% CI: 63-95) in HC
      (P < 0.001). In BCS/PVT, CD11b neutrophil expression had 90% specificity and 100%
      sensitivity for the association with PV. Finally, PV patients had higher
      oxidative burst and PNC than T-nPV patients or HC (P < 0.05). These results
      support a role for neutrophils in BCS/PVT secondary to PV and indicate that
      neutrophil CD11b expression could be of use for PV screening in BCS/PVT patients.

PMID- 14717781
TI  - A patient homozygous for a Gly354Cys mutation in factor VII that results in
      severely impaired secretion of the molecule, but not complete deficiency.
AB  - We investigated the molecular basis of factor VII (FVII) deficiency in a Japanese
      woman who suffered occasional epistaxis. The patient had low levels of both FVII
      coagulant activity (FVII:C) and antigen (FVII:Ag) (5.0% and 7.3% of normal
      controls respectively). DNA sequence analysis of the FVII gene showed that the
      patient was homozygous for a mutation that resulted in a Cys for Gly354
      substitution, a novel missense mutation in the catalytic domain. Haplotype
      analysis showed that this missense mutation was inherited from her consanguineous
      parents. Transient expression experiments showed that secreted FVII Cys354,
      FVII:C and FVII:Ag levels in conditioned media were reduced to 4% and 5%,
      respectively, of levels secreted from wild-type FVII. However, the intracellular
      FVII Cys354 was 67% that of normal recombinant protein. Immunohistochemical
      analysis showed that intracellular FVII:Ag from FVII 354Cys was present diffusely
      throughout the cytoplasm. Substitution of FVII 354Gly with amino acids other than
      Cys (Arg, Asp, Ser and Phe), did not produce a phenotype similar to FVII
      Cys354Gly. Molecular modelling indicated that FVII Gly354 was located outside the
      FVII heavy chain, and that Cys135 in the EGF2 domain, Cys262 in the catalytic
      domain and Cys127 all exist within 10 A of Gly354. Therefore, we propose that the
      introduction of an additional free cysteine residue in the FVII molecule results
      in the formation of illegitimate disulphide bonds and a mis-folded domain,
      leading to defective secretion.

PMID- 14717782
TI  - Genetic variability of von Willebrand factor and risk of coronary heart disease:
      the Rotterdam Study.
AB  - The von Willebrand factor (VWF) may be causally associated with coronary heart
      disease (CHD) or merely be a marker of endothelial damage. The G allele of the 
      1793 C/G promoter polymorphism in the VWF gene has been associated with higher
      plasma levels of VWF. To investigate whether VWF has a causal role in CHD, we
      designed a case-cohort study, including 352 subjects with CHD and a random cohort
      (n = 736), and prospectively examined the association of the -1793 C/G
      polymorphism with CHD in subjects with and without advanced atherosclerosis. All
      subjects were </=75 years of age and participating in the population-based
      Rotterdam Study. Atherosclerosis was assessed by the ankle-arm index. Among
      subjects with advanced atherosclerosis, heterozygous and homozygous carriers of
      the G allele had a 3.5 (1.2-10.2) and 1.5 (0.4-5.7) fold increased risk of CHD
      respectively, compared with C/C homozygotes. The hazard ratio was 2.6 (1.0-6.8)
      for carriers of at least one copy of the G allele versus non-carriers. No
      associations were found in the absence of advanced atherosclerosis. In
      conclusion, this study suggests that the G allele of the -1793 C/G polymorphism
      in the VWF gene is associated with an increased risk of CHD, but only in subjects
      with advanced atherosclerosis.

PMID- 14717783
TI  - Dietary vitamin K influences intra-individual variability in anticoagulant
      response to warfarin.
AB  - The relationship between dietary intake of vitamin K, fat, plasma vitamin K
      concentrations and anticoagulation response to warfarin within individuals, as
      well as the contribution of dietary vitamin K to differences in warfarin dose
      requirements between individuals were investigated in 53 patients on warfarin
      therapy who had stably controlled anticoagulation. Each patient completed a
      dietary record of all foods consumed on a daily basis for 4 weeks. Each week a
      blood sample was taken for measurement of the international normalized ratio
      (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations.
      The patients' genotype for CYP2C9 was also determined. Regression analysis of the
      data showed that, for each increase of 100 microg in the daily dietary intake of
      vitamin K averaged over 4 d, the INR was reduced by 0.2. There was no correlation
      between warfarin daily dose and average daily dietary vitamin K intake when
      calculated over 28 d. The regression model for warfarin dose showed that, while
      dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%)
      significantly contributed to inter-patient variability in warfarin dose
      requirements. A consistent intake of vitamin K could reduce intrapatient
      variability in anticoagulation response and thus improve the safety of warfarin
      therapy.

PMID- 14717784
TI  - Standardization of the endogenous thrombin potential measurement: how to minimize
      the effect of residual platelets in stored plasma.
AB  - Platelet contamination in stored plasma may affect coagulation assays, including
      the endogenous thrombin potential (ETP), which has been proposed for the
      investigation of hyper- and hypo-coagulability. The current recommendation of
      filtering plasma before freezing cannot be always met. This study provides
      evidence that filtering frozen plasma after thawing, prior to testing, may help
      to eliminate the unwanted effect of residual platelets on the ETP. This may have
      important implications in future studies, as the ETP could be determined with
      plasma that have been collected without precautions relating to platelet
      contamination, as is the case for plasmas collected in epidemiological studies.

PMID- 14717785
TI  - Cdk-inhibitors and exit from quiescence in primitive haematopoietic cell subsets.
AB  - Prolonged quiescence of haematopoietic stem cells has been proposed to support
      durable haematopoiesis through clonal succession. Genetic experiments in mice
      have implicated the cyclin-dependent kinase inhibitor (cdki) p21Waf1 in
      sustaining stem cell quiescence, and the cdki p27Kip1 in inhibiting the expansion
      of more mature progenitor cells. The expression of these inhibitory proteins in
      human haematopoietic stem cell candidates has not hitherto been studied. We
      describe a rare subpopulation (3 x 10-7 umbilical cord mononuclear cells) of
      lineage-negative cells that exhibited sustained resistance over months to
      cytokine-induced cycling, and characterized the expression of p21Waf1 and p27Kip1
      proteins in these cells. Whereas p27Kip1 was uniformly expressed in these cells,
      the expression of p21Waf1 in this population and in lineage-negative CD34+ cells
      was variable. For this rare subset of cells exhibiting prolonged quiescence,
      p21Waf1 may be dispensable and p27Kip1 necessary for growth arrest.

PMID- 14717786
TI  - The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF
      and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures.
AB  - Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co
      cultured to model in vitro the interactions between myeloma and endothelium, and
      treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs,
      phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent
      assay were used to assess production of two key cytokines--vascular endothelial
      growth factor (VEGF) and interleukin-6 (IL-6)--and apoptosis in co-cultured
      HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs,
      while IL-6 was almost exclusively produced by endothelial cells. In co-culture,
      there was significant up-regulation of VEGF and IL-6 production compared with the
      sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited
      production of both cytokines in co-cultures, with CC-10004 being more potent than
      CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co
      cultured myeloma cells was significantly lower than in those cultured separately,
      suggesting that co-culture partially protected myeloma cells from drug-induced
      apoptosis. This protective effect was probably due to IL-6 produced by
      endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody,
      but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their
      anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6
      production by interacting myeloma and endothelium and induction of myeloma cell
      apoptosis.

PMID- 14717787
TI  - Platelet microparticles induce angiogenesis in vitro.
AB  - Platelet microparticles (PMP) are endogenous substances generated during the
      coagulation process in a hypercoagulable state. This study demonstrated that PMP
      promote the proliferation and survival, migration, and tube formation in human
      umbilical vein endothelial cells (HUVEC). Heat-treated PMP did not significantly
      decrease the angiogenic activity in HUVEC compared with that of the untreated
      PMP. Meanwhile when PMP were treated with activated charcoal, a procedure known
      to remove the lipid growth factors, the angiogenic activity was significantly
      reduced. These results suggest that the lipid component(s) of the PMP may be
      major active factor(s) and that protein component(s) may be minor contributor(s).
      PMP were also shown to augment endothelial progenitor cell differentiation in
      peripheral blood mononuclear cells. In addition, PMP-stimulated proliferation,
      chemotaxis and tube formation of the HUVEC was mediated via the Pertussis toxin
      sensitive G protein, extracellular signal-regulated kinase and the
      phosphoinositide 3-kinase pathway. Herein, a new action of PMP was demonstrated
      to be a potent angiogenic stimulator. It is expected that in pathological states
      such as a growing tumour, PMP shed from the circulating platelets may reach
      adequate concentrations and that the elevated levels of PMP could contribute to
      florid formation of new blood vessels.

PMID- 14717788
TI  - Magnetic resonance screening of iron status in transfusion-dependent beta
      thalassaemia patients.
AB  - The clinical utility of dual sequence (T1- and T2-weighted) magnetic resonance
      (MR) imaging in estimating liver iron concentration (LIC) in 32 transfusion
      dependent beta-thalassaemia major (24 females; age 18.5+/-5.9 years) patients on
      desferrioxamine was evaluated. Signal intensity ratios (SIR) between liver,
      spleen and pancreas to psoas muscle were determined on both sequences.
      Relationships between clinical and MR parameters, and accuracy of SIR thresholds
      in determining adequacy of chelation from LIC were analysed. Liver T1- and T2-SIR
      were related to LIC (P < 0.001). T1-SIR < 0.60 predicted severe iron overload
      (LIC > 15 mg/g) with sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) of 100%, 87%, 33% and 100% respectively. T2
      SIR < 0.1 yielded 100% sensitivity, 93% specificity, 50% PPV and 100% NPV. T1-SIR
      > or = 1.1 predicted LIC < 7 mg/g with 69% sensitivity, 88% specificity, 85% PPV
      and 74% NPV. T2-SIR > or = 0.20 yielded 56.5% sensitivity, 94% specificity, 90%
      PPV and 71% NPV. LIC correlated with liver T1-SIR, liver T2-SIR and serum
      ferritin (r = -0.76, -0.65, 0.47, respectively; P < 0.01). Serum ferritin was
      inversely related to liver T1-SIR, liver T2-SIR and spleen T2-SIR (r = -0.35, 
      0.43, -0.40, respectively; P < 0.05). Mean total transfusion burden was not
      related to any MR parameter. Although neither MR sequence was a highly accurate
      predictor of LIC, SIR thresholds are useful to determine presence of iron
      overload and adequacy of chelation treatment.

PMID- 14717789
TI  - Reactive oxygen species and phosphatidylserine externalization in murine sickle
      red cells.
AB  - Due to their role in oxygen transport and the presence of redox active
      haemoglobin molecules, red blood cells (RBC) generate relatively high levels of
      reactive oxygen species (ROS). To counteract the potential deleterious effects of
      ROS, RBCs have a well-integrated network of anti-oxidant mechanisms to combat
      this oxidative stress. ROS formation is increased in sickle-cell disease (SCD)
      and our studies in a murine SCD model showed a significant increase in the
      generation of ROS when compared with normal mice. Our data also indicated that
      murine sickle RBCs exhibit a significantly increased ATP catabolism, partly due
      to the increased activity of glucose-6-phosphate dehydrogenase and glutathione
      reductase to regenerate intracellular glutathione (GSH) levels to neutralize the
      adverse milieu of oxidative stress. Higher ATP consumption by the murine sickle
      RBCs, together with the increased ROS formation and impairment of the
      aminophospholipid translocase or flipase may underlie the exposure of
      phosphatidylserine on the surface of these cells.

PMID- 14717790
TI  - The use of a risk group stratification in the management of invasive fungal
      infection: a prospective validation.

PMID- 14717800
TI  - Ethical conflicts for physicians treating ESRD patients.
AB  - Managing an end-stage renal disease (ESRD) patient is complex and presents many
      ethical challenges for the physician. Ownership of dialysis facilities has
      shifted over the past decade from largely nonprofit organizations to large
      companies whose shareholders are primarily interested in the profitability of
      their investments rather than the well-being of the patients being treated.
      Furthermore, market forces rather than scientific questions that need to be
      answered now drive much of the research regarding patients with ESRD. These
      developments have created ethical dilemmas for treating physicians. This
      editorial describes some of these ethical challenges and expresses the point of
      view that the doctor-patient relationship and its ethical imperatives are more
      important than company profit and loss statements.

PMID- 14717801
TI  - Treating intractable venous stenosis: present and future therapy.
AB  - The widespread use of percutaneous angioplasty for venous stenoses has lengthened
      the functional life span of hemodialysis access, while preserving precious venous
      capital. A subset of dialysis patients with dysfunctional access sites will
      harbor stenoses which are intractable, in that they fail to respond to
      conventional balloon angioplasty or recur in the weeks following angioplasty.
      This editorial discusses various endovascular approaches to the management of
      intractable venous stenosis as well as promising future therapies.

PMID- 14717802
TI  - The value of vaccination in chronic kidney disease.
AB  - There has been much attention directed toward the high mortality of patients with
      end-stage renal disease (ESRD), with much of the focus on cardiovascular disease.
      However, infectious disease is the second most common cause of death in late
      stage chronic kidney disease (CKD) patients. Although CKD patients are
      immunocompromised, some vaccines such as influenza, retain their efficacy and
      reduce infection rates with a standard immunization schedule. Other vaccines,
      such as hepatitis B and pneumococcal vaccines, require more frequent and/or
      higher doses to produce and maintain protective antibody levels. Attention has
      recently been given to the efficacy of influenza vaccination in ESRD patients in
      reducing morbidity and mortality. Centers with vaccination protocols have
      demonstrated reduced infection rates and resultant decreased morbidity and
      mortality. It could be extrapolated from this that widespread vaccination would
      reduce the total cost of ESRD patient care, and potentially improve patient well
      being. However, vaccination appears to be underutilized in CKD patients, and it
      is a readily available intervention to improve outcomes.

PMID- 14717803
TI  - What common practices in dialysis units can be altered to improve patient care?

PMID- 14717804
TI  - What common practices in dialysis units can be altered to improve patient care?

PMID- 14717805
TI  - What common practices in dialysis units can be altered to improve patient care?

PMID- 14717806
TI  - What common practices in dialysis units can be altered to improve patient care?

PMID- 14717807
TI  - What common practices in dialysis units can be altered to improve patient care?

PMID- 14717809
TI  - Dose of dialysis in acute renal failure.
AB  - Acute renal failure (ARF) is a cause of significant morbidity and mortality.
      Despite advances in supportive care, outcomes in ARF have improved little over
      the past decades. The primary goals in management of patients with ARF are to
      optimize hemodynamic and volume status, minimize further renal injury, correct
      metabolic abnormalities, and permit adequate nutrition. Renal replacement therapy
      (RRT) is often required to achieve these goals while awaiting renal recovery, but
      the optimal dose of dialysis in patients with ARF is not known. Extrapolation of
      required dialysis dose from recommendations in chronic dialysis is unlikely to be
      appropriate because of the lack of a steady state and differences in distribution
      volume of urea that are intrinsic to ARF. The prescribed dialysis dose in ARF is
      often low, and actual delivered dose is often even less than prescribed. Delivery
      of dialysis in ARF is often hampered by the patient's hypercatabolic state,
      hemodynamic instability, and volume status, as well as suboptimal vascular access
      with temporary venous catheters. The impact of intermittent hemodialysis (IHD)
      versus continuous renal replacement therapy (CRRT) on outcomes in ARF is also not
      clear. Patient disease severity impacts more than dialysis modality in patient
      outcome, but when patients are stratified for equal disease severity, CRRT may
      have potential benefits over IHD in terms of patient survival, fluid and
      metabolic control, and renal recovery. Strategies associated with improved
      outcomes that have emerged thus far in ARF are to aim for a time-averaged blood
      urea nitrogen (BUN) of less than 60 mg/dl with IHD, varying IHD frequency as
      necessary, or to achieve a minimum ultrafiltration rate of 35 ml/kg/hr with CRRT.

PMID- 14717808
TI  - Nondialytic management of hyperkalemia and pulmonary edema among end-stage renal
      disease patients: an evaluation of the evidence.
AB  - Congestive heart failure (CHF) and hyperkalemia are the two leading reasons for
      emergency dialysis among individuals with end-stage renal disease (ESRD). While
      hemodialysis provides definitive treatment of both hyperkalemia and volume
      overload among ESRD patients, for those who present outside of "regular dialysis
      hours," institution of dialysis may be delayed. Nondialytic management can be
      instituted immediately and should be the initial therapy in the management of
      hyperkalemia and CHF in these individuals. Current available evidence does not
      allow conclusions as to whether treatment with nondialytic strategies alone
      results in different outcomes than nondialytic strategies coupled with emergent
      hemodialysis. Therefore, whether or not nondialytic management alone is
      appropriate remains a matter of individual judgment that should be decided on a
      case-by-case basis.

PMID- 14717810
TI  - Methods of assessment of volume status and intercompartmental fluid shifts in
      hemodialysis patients: implications in clinical practice.
AB  - Determining dry weight and assessing extracellular fluid volume in hemodialysis
      (HD) patients is one of the greatest challenges to practicing nephrologists. The
      clinical examination has limited accuracy, so different strategies have been
      investigated to aid in this evaluation. Biochemical markers of volume overload
      (ANP, BNP, cGMP) are fraught with excessive variability and poor correlation with
      volume status. Inferior vena cava ultrasound is effective, but cumbersome and
      costly. Bioimpedance measurements of intra- and extracellular water have
      significant shortcomings when used as isolated measurements, but can be useful in
      following trends over time and have been shown to improve intradialytic symptoms
      and blood pressure control. Continuous blood volume monitoring is helpful in
      preventing intradialytic hypotension and may help identify patients who are
      volume overloaded and need increased ultrafiltration. In this review we discuss
      these different techniques and other developments in the evaluation of dry weight
      and volume status, which may enhance our ability to improve patient stability and
      well-being during HD sessions.

PMID- 14717811
TI  - Eating behavior disorders in uremia: a question of balance in appetite
      regulation.
AB  - Eating and appetite disorders are frequent complications of the uremic syndrome
      which contribute to malnutrition in dialysis patients. The data suggest that
      uremic anorexia may occur with or without abdominal and visceral fat accumulation
      despite a lower food intake. This form of obesity (i.e., with low food intake and
      malnutrition) is more common in dialysis patients than obesity with high food
      intake. This article reviews the current knowledge regarding mechanisms
      responsible for appetite regulation in normal conditions and in uremic patients.
      Anorexia in dialysis patients has been historically considered as a sign of
      uremic toxicity due to "inadequate" dialysis as judged by uncertain means
      ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and
      others). We propose the tryptophan-serotonin hypothesis, based on a uremia
      induced disorder in patients' amino acid profile--low concentrations of large
      neutral and branched-chain amino acids with high tryptophan levels. A high rate
      of tryptophan transport across the blood-brain barrier increases the synthesis of
      serotonin, a major appetite inhibitor. Inflammation may also play a role in the
      genesis of anorexia and malnutrition. For example, silent infection with
      Helicobacter pylori may be a source of cytokines with cachectic action; its
      eradication improves appetite and nutrition. The evaluation of appetite should
      take into account cultural and social aspects. Uremic patients showed a universal
      trend to carbohydrate preference and red meat refusal compared to healthy people.
      In contrast, white meat was less problematic. Uremic patients also have a
      remarkable attraction for citrics and strong flavors in general. Eating
      preferences or refusals have been related to the predominance of some appetite
      peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen)
      are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an
      orexigen) with repeated food intake. Obesity and elevated body mass index often
      falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia
      state), disorders in the regulation of fat distribution (insulin, leptin, insulin
      like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin,
      lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3
      adrenoreceptors) may cause abdominal fat accumulation without an increase in
      appetite. Finally, appetite regulation in uremia is highly complex. Disorders in
      adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced
      inflammatory end products, and central nervous system changes may all play a
      role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic
      state derived from a high concentration of tryptophan and low branched-chain
      amino acids.

PMID- 14717812
TI  - Radioactive 131I use in end-stage renal disease: nightmare or nuisance?
AB  - Patients with end-stage renal disease (ESRD) are at risk of prolonged radiation
      exposure during therapy with radioactive iodine (131I) because it is normally
      renally excreted. However, 131I is dialyzable and exposure can be monitored with
      a standard Geiger counter during dialysis. We present two cases of thyroid
      carcinoma in patients with ESRD who were treated successfully with 131I while
      continuing chronic hemodialysis (HD). In each case, single HD treatments of 3 and
      4 hours performed approximately 20 hours after the administration of 131I
      resulted in an 80% and 70% reduction in total body radiation levels,
      respectively. In both cases, Geiger counter measurements after HD following 131I
      administration revealed levels less than 3 mR/hr, allowing safe discharge from
      the hospital in a timely manner. All contaminated waste was disposed of by the
      hospital's Department of Radiation Safety. Postdialysis monitoring revealed no
      residual radiation contamination of the HD machine or radiation exposure to the
      dialysis staff. Hemodialyzer reuse was suspended until monitoring demonstrated no
      appreciable evidence of radioactivity in these spent supplies. HD is a critical
      aspect in the treatment of patients with ESRD receiving 131I and can safely be
      administered with close planning between the HD staff and the staff of radiation
      safety.

PMID- 14717813
TI  - Intravenous iron and the risk of infection in end-stage renal disease patients.
AB  - Oral iron is typically insufficient for the iron deficiency of hemodialysis
      patients. Intravenous (IV) iron is well tolerated by most patients and non
      dextran-containing iron preparations are associated with few allergic reactions.
      However, there is the potential for an increased risk of infection with IV iron
      that appears to increase bacterial growth as well as inhibit the host's innate
      immune response to bacterial infection. Clinical studies suggest a link between
      iron therapy and infection. Practicing nephrologists should be aware of this
      issue, but should not hesitate to use IV iron in iron-deficient patients while
      avoiding the development of iron overload and administration of iron to patients
      who have active infection.

PMID- 14717814
TI  - Port catheter placement by nephrologists in an interventional nephrology training
      program.
AB  - We retrospectively reviewed all subcutaneous single- and double-lumen port
      catheters (PCs) inserted by interventional nephrologists at our institution to
      determine the success rate, immediate and late complications, and functional
      life. From January 2000 to August 2002, 187 PCs were placed in 187 patients (42%
      males, 51% Caucasians, mean age 50 +/- 14 years). There were no immediate
      complications related to the procedure such as hemorrhage, pulmonary embolism, or
      pneumothorax. There were a total of 35,078 catheter-days of follow-up. Sixteen
      catheters were removed during the observation period: three because of infection,
      seven after completion of chemotherapy, and six for other reasons. The remaining
      PCs are either functioning or the patients have died. The initial success rate
      was 100%. Kaplan-Meier analysis showed a 30-day survival of 97% and a 1-year
      survival of 92%. Interventional nephrologists, who have adequate training in
      central venous tunneled cuffed catheter placements, can successfully place PCs,
      with excellent success and minimal complications.

PMID- 14717815
TI  - Preliminary evaluation of a valved introducer sheath for the insertion of
      tunneled hemodialysis catheters.
AB  - This brief technical report describes our initial experience using the FlowGuard
      valved introducer sheath during the insertion of tunneled hemodialysis catheters
      in 15 patients. The incorporation of a silicone valve into the introducer sheath
      is intended to minimize blood loss and decrease the risk of air embolism during
      the catheter insertion procedure. Our preliminary experience demonstrated that
      the FlowGuard sheath is a substantial improvement when compared to standard
      introducer sheaths. However, an asymptomatic air embolus did occur in one
      patient. This article describes several caveats for the use of this new product.

PMID- 14717816
TI  - Hepatic drug metabolism in chronic renal failure.

PMID- 14717819
TI  - Thrombosis in end-stage renal disease.

PMID- 14717821
TI  - Argatroban use in dialysis patients.

PMID- 14717822
TI  - Bravo!--Renal physicians in conflict.

PMID- 14717824
TI  - How the brain processes causal inferences in text.
AB  - Theoretical models of text processing, such as the construction-integration
      framework, pose fundamental questions about causal inference making that are not
      easily addressed by behavioral studies. In particular, a common result is that
      causal relatedness has a different effect on text reading times than on memory
      for the text: Whereas reading times increase linearly as causal relatedness
      decreases, memory for the text is best for events that are related by a moderate
      degree of causal relatedness and is poorer for events with low and high
      relatedness. Our functional magnetic resonance imaging study of the processing of
      two-sentence passages that varied in their degree of causal relatedness suggests
      that the inference process can be analyzed into two components, generation and
      integration, that are subserved by two large-scale cortical networks (a reasoning
      system in dorsolateral prefrontal cortex and the right-hemisphere language
      areas). These two cortical networks, which are distinguishable from the classical
      left-hemisphere language areas, approximately correspond to the two functional
      relations observed in the behavioral results.

PMID- 14717825
TI  - Unemployment alters the set point for life satisfaction.
AB  - According to set-point theories of subjective well-being, people react to events
      but then return to baseline levels of happiness and satisfaction over time. We
      tested this idea by examining reaction and adaptation to unemployment in a 15
      year longitudinal study of more than 24,000 individuals living in Germany. In
      accordance with set-point theories, individuals reacted strongly to unemployment
      and then shifted back toward their baseline levels of life satisfaction. However,
      on average, individuals did not completely return to their former levels of
      satisfaction, even after they became reemployed. Furthermore, contrary to
      expectations from adaptation theories, people who had experienced unemployment in
      the past did not react any less negatively to a new bout of unemployment than did
      people who had not been previously unemployed. These results suggest that
      although life satisfaction is moderately stable over time, life events can have a
      strong influence on long-term levels of subjective well-being.

PMID- 14717826
TI  - The peculiar longevity of things not so bad.
AB  - Intense hedonic states trigger psychological processes that are designed to
      attenuate them, and thus intense states may abate more quickly than mild states.
      Because people are unaware of these psychological processes, they may mistakenly
      expect intense states to last longer than mild ones. In Study 1, participants
      predicted that the more they initially disliked a transgressor, the longer their
      dislike would last. In Study 2, participants predicted that their dislike for a
      transgressor who hurt them a lot would last longer than their dislike for a
      transgressor who hurt them a little, but precisely the opposite was the case. In
      Study 3, participants predicted that their dislike for a transgressor who hurt
      them a lot would last longer than their dislike for a transgressor who hurt
      someone else a lot, but precisely the opposite was the case. These errors of
      prediction are discussed as instances of a more general phenomenon known as the
      region-beta paradox.

PMID- 14717827
TI  - Exogenous spatial attention influences figure-ground assignment.
AB  - In a hierarchical stage account of vision, figure-ground assignment is thought to
      be completed before the operation of focal spatial attention. Results of previous
      studies have supported this account by showing that unpredictive, exogenous
      spatial precues do not influence figure-ground assignment, although voluntary
      attention can influence figure-ground assignment. However, in these studies,
      attention was not summoned directly to a region in a figure-ground display. In
      three experiments, we addressed the relationship between figure-ground assignment
      and visuospatial attention. In Experiment 1, we replicated the finding that
      exogenous precues do not influence figure-ground assignment when they direct
      attention outside of a figure-ground stimulus. In Experiment 2, we demonstrated
      that exogenous attention can influence figure-ground assignment if it is directed
      to one of the regions in a figure-ground stimulus. In Experiment 3, we
      demonstrated that exogenous attention can influence figure-ground assignment in
      displays that contain a Gestalt figure-ground cue; this result suggests that
      figure-ground processes are not entirely completed prior to the operation of
      focal spatial attention. Exogenous spatial attention acts as a cue for figure
      ground assignment and can affect the outcome of figure-ground processes.

PMID- 14717828
TI  - Visual sensing without seeing.
AB  - It has often been assumed that when we use vision to become aware of an object or
      event in our surroundings, this must be accompanied by a corresponding visual
      experience (i.e., seeing). The studies reported here show that this assumption is
      incorrect. When observers view a sequence of displays alternating between an
      image of a scene and the same image changed in some way, they often feel (or
      sense) the change even though they have no visual experience of it. The
      subjective difference between sensing and seeing is mirrored in several
      behavioral differences, suggesting that these are two distinct modes of conscious
      visual perception.

PMID- 14717829
TI  - Lightness constancy in the presence of specular highlights.
AB  - Visible surfaces in a natural environment often have multiple components of
      reflectance, including a diffuse component, by which light is scattered
      isotropically in all possible directions, and a specular component, by which
      light is reflected anisotropically within a limited range of directions. The
      research described in the present article was designed to investigate how these
      different components of reflectance influence the perception of lightness. Human
      observers were presented with shaded images of smoothly curved surfaces and asked
      to compare the relative lightness of different surface regions whose diffuse and
      specular components of luminance were independently manipulated. The results
      revealed that observers are able to discount the presence of specular highlights
      so that the relative lightness among different regions is determined almost
      entirely by the diffuse component of surface reflectance.

PMID- 14717830
TI  - The perception of doubly curved surfaces from anisotropic textures.
AB  - Most existing computational models of the visual perception of three-dimensional
      shape from texture are based on assumed constraints about how texture is
      distributed on visible surfaces. The research described in the present article
      was designed to investigate how violations of these assumptions influence human
      perception. Observers were presented with images of smoothly curved surfaces
      depicted with different types of texture, whose distribution of surface markings
      could be both anisotropic and inhomogeneous. Observers judged the pattern of
      ordinal depth on each object by marking local maxima and minima along designated
      scan lines. They also judged the apparent magnitudes of relative depth between
      designated probe points on the surface. The results revealed a high degree of
      accuracy and reliability in all conditions, except for a systematic
      underestimation of the overall magnitude of surface relief. These findings
      suggest that human perception of three-dimensional shape from texture is much
      more robust than would be reasonable to expect based on current computational
      models of this phenomenon.

PMID- 14717831
TI  - The new and improved two-sample T test.
AB  - This article considers the problem of comparing two independent groups in terms
      of some measure of location. It is well known that with Student's two-independent
      sample t test, the actual level of significance can be well above or below the
      nominal level, confidence intervals can have inaccurate probability coverage, and
      power can be low relative to other methods. A solution to deal with heterogeneity
      is Welch's (1938) test. Welch's test deals with heteroscedasticity but can have
      poor power under arbitrarily small departures from normality. Yuen (1974)
      generalized Welch's test to trimmed means; her method provides improved control
      over the probability of a Type I error, but problems remain. Transformations for
      skewness improve matters, but the probability of a Type I error remains
      unsatisfactory in some situations. We find that a transformation for skewness
      combined with a bootstrap method improves Type I error control and probability
      coverage even if sample sizes are small.

PMID- 14717832
TI  - The basic-level convergence effect in memory distortions.
AB  - Whereas most previous findings suggest that memory may become more abstract over
      time, so that memory for gist outlasts verbatim memory, there are findings
      suggesting that abstract information may sometimes be instantiated in more
      specific terms. In this study, we examined the hypothesis that retained
      information tends to converge at an intermediate level of abstractness-the basic
      level. In two experiments, we found bidirectional, symmetrical shifts in the
      memory for story material: Participants presented with either subordinate terms
      (e.g., sports car) or superordinate terms (e.g., vehicle) tended to falsely
      report basic-level terms (e.g., car) instead. This pattern emerged for both
      recall and recognition memory tests, at both immediate and delayed testing, and
      under free and forced reporting. The results suggest that the basic level, which
      has been considered cognitively optimal for perception, categorization, and
      communication, is also the preferred level for retaining episodic information in
      memory.

PMID- 14717833
TI  - Hearing cheats touch, but less in congenitally blind than in sighted individuals.
AB  - The principles of cross-modal integration were investigated with an auditory
      tactile illusion in sighted and congenitally blind adults. Participants had to
      judge the number of rapidly presented tactile stimuli, which were presented
      together with task-irrelevant sounds. When one tactile stimulus was accompanied
      by more than one tone, participants reported perceiving more than a single touch.
      This illusion was more pronounced in sighted than congenitally blind
      participants. Given that the congenitally blind were more precise in judging the
      number of tactile stimuli in a control condition without tones, the present data
      are in accordance with a modality-appropriateness account suggesting that
      interference by a task-irrelevant modality is reduced if processing accuracy of
      the task-relevant modality is high.

PMID- 14717834
TI  - No blindness for things that do not change.
AB  - It is well known that under normal circumstances, human observers are able to
      detect a visual change (a luminance transient) in the outside world very easily.
      This study demonstrated that observers are also easily able to detect a
      nonchanging element if it is located in a display containing multiple elements
      that do change. That is, a nonchanging element popped out from a display
      containing multiple changing elements (luminance transients). The efficient
      detection of the nonchanging element may be due to temporal grouping created by
      the dynamic character of the stimulus display.

PMID- 14717835
TI  - Mimicry and prosocial behavior.
AB  - Recent studies have shown that mimicry occurs unintentionally and even among
      strangers. In the present studies, we investigated the consequences of this
      automatic phenomenon in order to learn more about the adaptive function it
      serves. In three studies, we consistently found that mimicry increases prosocial
      behavior. Participants who had been mimicked were more helpful and generous
      toward other people than were nonmimicked participants. These beneficial
      consequences of mimicry were not restricted to behavior directed toward the
      mimicker, but included behavior directed toward people not directly involved in
      the mimicry situation. These results suggest that the effects of mimicry are not
      simply due to increased liking for the mimicker, but are due to increased
      prosocial orientation in general.

PMID- 14717839
TI  - Tanning devices--fast track to skin cancer?
AB  - The use of UVB and/or UVA emitting devices for cosmetic tanning is widespread in
      Western populations including young people and is especially prevalent in
      females. Several epidemiological studies, although not all, have shown a
      significant relationship between the use of tanning devices and malignant
      melanoma after, in some cases, adjustment for confounding factors such as solar
      ultraviolet radiation (UVR) exposure. A relationship between solar exposure,
      especially intermittent exposure, and malignant melanoma is well established so
      it is not surprising that a similar connection has been reported for the use of
      tanning devices. Several epidemiological studies show that childhood exposure to
      sunlight is a risk factor for malignant melanoma and this may also be the case
      for the use of tanning devices, especially if sunburns are obtained. Some studies
      have evaluated the relationship between the use of tanning devices and non
      melanoma skin cancer and at least one has suggested an association. The use of
      tanning devices by a substantial minority of young people is a worrying trend in
      terms of a likely increased incidence of malignant melanoma, and possibly non
      melanoma cancers in the future. Although two recent reviews by epidemiologists
      conclude that a clear link between tanning devices and malignant melanoma is yet
      to be proven, there is a strong case for effective legislation to prohibit the
      use of tanning devices by people under 18 yr of age.

PMID- 14717840
TI  - In situ hybridization: an informative technique for pigment cell researchers.
AB  - Many cellular events are regulated at the transcriptional level. Recent technical
      advances such as DNA microarray have made it possible to determine mRNA profiles
      of cultured cells or tissues. However, since it is still impossible to completely
      simulate the in vivo environment in culture conditions, mRNA profiles of cultured
      cells are not perfect representatives of original cells. Furthermore, for cells
      that exist at lower densities, mRNA profiling using tissue samples would be
      difficult. By using tissue in situ hybridization, mRNA levels of genes in tissues
      can be determined at cellular resolution. Although throughput of tissue in situ
      hybridization is not high enough for mRNA profiling, it may be sufficient to
      investigate temporal/spatial expression profiles of genes that are known to be
      important or found to be interesting in high-throughput transcriptome/proteome
      analyses. Recent technical advances have made it easier for everybody to perform
      tissue in situ hybridization using normal experimental instruments with
      sufficient sensitivity to detect most genes. Although this technique has been
      utilized mainly in developmental biology, it will be fully advantageous when
      combined with high-throughput comprehensive transcriptome/proteome analyses.

PMID- 14717841
TI  - Expression of THR1, a 1,3,8-trihydroxynaphthalene reductase gene involved in
      melanin biosynthesis in the phytopathogenic fungus Bipolaris oryzae, is enhanced
      by near-ultraviolet radiation.
AB  - 1,3,8-Trihydroxynaphthalene (1,3,8-THN) reductase is involved in the production
      of fungal dihydroxynaphthalene (DHN) melanin. We isolated and characterized THR1,
      a gene encoding 1,3,8-THN reductase, from the phytopathogenic fungus Bipolaris
      oryzae. Sequence analysis showed that THR1 encodes a putative protein of 267
      amino acids having a molecular weight of 28.5 kDa and 68-98% sequence identity to
      other fungal 1,3,8-THN reductases. Targeted disruption of the THR1 gene showed
      that it is essential for melanin biosynthesis in B. oryzae. Northern blot
      analysis showed that THR1 transcripts are constitutively expressed during normal
      growth but are specifically enhanced by near-ultraviolet (NUV) radiation in a
      dose-dependent manner. These results indicate that THR1 expression is
      transcriptionally enhanced by NUV radiation in B. oryzae.

PMID- 14717842
TI  - Clinical and histopathological characterization of cutaneous melanomas in the
      melanoblastoma-bearing Libechov minipig model.
AB  - Spontaneous animal tumors appear to be highly suitable models to study human
      oncology and cancer therapy. The aim of this study was to characterize the
      clinical and histological features of hereditary melanocytic lesions found in the
      French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc
      crossbreeds. Clinically, we discriminated between three types of melanocytic skin
      lesions, which offer a lesion continuum from lentigo to metastatic melanomas.
      More than 70% of these lesions appear on piglets before they are 3 months old and
      preferentially on homogeneous black coat piglets. The incidence of melanoma
      reaches 50% in MeLiM. Most of the highly invasive melanomas regressed
      spontaneously in the first year of the piglet's life and the regression was
      followed by hair, skin and iris depigmentation. A histopathological study was
      conducted according to the human melanoma classification. Except for lentigo
      maligna, we observed the three main types of human melanoma in swine [superficial
      spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM
      (59-67%). The histological events leading to total spontaneous regression are
      chronologically described. The genetic predisposition, the high incidence of
      melanoma, the clinical and histopathological features similar to the human
      disease and the high rate of spontaneous regression offer an opportunity to use
      this model for studying genetic events controlling melanoma development and
      regression and the biological mechanisms involved in oncogenesis and anti
      cancerous self-defense.

PMID- 14717843
TI  - Correction of defective early tyrosinase processing by bafilomycin A1 and
      monensin in pink-eyed dilution melanocytes.
AB  - Mutations in the human P gene result in oculocutaneous albinism type 2, the most
      common form of albinism. Mouse melan-p1 melanocytes, cultured from mice null at
      the homologous pink-eyed dilution (p) locus, exhibit defective melanin
      production. A variety of compounds including tyrosine, NH4Cl, bafilomycin A1,
      concanamycin, monensin, and nigericin are capable of restoring melanin synthesis
      in these cells. In the current study, we investigated the subcellular effects of
      bafilomycin A1 and monensin treatment of melan-p1 cells. Both agents play two
      roles in the processing of tyrosinase (Tyr) in melan-p1 cells. First, combined
      glycosidase digestion and immunoblotting analysis showed that these agents reduce
      levels of Tyr retained in the endoplasmic reticulum (ER) and facilitate the
      release of Tyr from the ER to the Golgi. Secondly, treatment with these compounds
      resulted in the stabilization of Tyr. Surprisingly, induction of melanin
      synthesis corresponds more closely with diminution of ER-retained Tyr, rather
      than the absolute amount of Tyr. Our results suggest that bafilomycin A1 and
      monensin induce melanin synthesis in melan-p1 cells mainly by facilitating Tyr
      processing from the ER to the Golgi by increasing the pH in either the ER or the
      ER-Golgi intermediate compartment.

PMID- 14717845
TI  - Hepatocyte growth factor controls the proliferation of cultured epidermal
      melanoblasts and melanocytes from newborn mice.
AB  - Mouse epidermal melanoblasts and melanocytes preferentially proliferated from
      disaggregated epidermal cell suspensions derived from newborn mouse skin in a
      serum-free melanocyte-proliferation medium (MDMD) and melanoblast-proliferation
      medium (MDMDF) supplemented with dibutyryl adenosine 3':5'-cyclic monophosphate
      (DBcAMP) and/or basic fibroblast growth factor (bFGF). Pure cultured primary
      melanoblasts and melanocytes were further cultured with MDMD/MDMDF supplemented
      with hepatocyte growth factor (HGF) from 14 days (keratinocyte depletion). The
      HGF increased the number of melanoblasts and melanocytes, but not the percentage
      of differentiated melanocytes in the melanoblast-melanocyte population in the
      absence of keratinocytes. Flow cytometry analysis showed that melanoblasts and
      melanocytes in the S and/or G2/M phases of the cell cycle were increased by the
      treatment with HGF. Moreover, an anti-HGF antibody supplemented to MDMD/MDMDF
      from the initiation of the primary culture (in the presence of keratinocytes)
      inhibited the proliferation of melanoblasts and melanocytes, but not the
      differentiation of melanocytes. These results suggest that HGF is a keratinocyte
      derived factor involved in regulating the proliferation of epidermal melanoblasts
      and melanocytes from newborn mice in cooperation with cAMP elevators and/or bFGF.

PMID- 14717844
TI  - A dominant negative mutant of microphthalmia transcription factor (MITF) lacking
      two transactivation domains suppresses transcription mediated by wild type MITF
      and a hyperactive MITF derivative.
AB  - Microphthalmia transcription factor (MITF) positively regulates transcription of
      differentiation-related genes in several cell lineages, including melanocytes.
      Recent data also indicate a new important role for MITF as a factor that appears
      to be required for survival of melanoma cells, suggesting a possibility that
      abrogation of MITF function in transformed melanocytes could lead to a decreased
      survival via attenuating anti-apoptotic signals. Therefore, to gain a better
      understanding of the role which MITF plays in melanoma cell survival, it is
      important to find efficient means of abolishing the transactivation of its target
      genes. Recently, a dominant negative MITF lacking the N-terminus has been shown
      to down-regulate tyrosinase and Trp1 expression in normal melanocytes and mouse
      B16 melanoma cells. Here, a dominant negative mutant of the melanocyte-specific
      isoform of MITF is described carrying deletions of both N- and C-terminal
      transactivation domains. Cotransfection of this mutant resulted in a complete
      inhibition of the wild type MITF function as tested on both the reporter-linked
      tyrosinase promoter and an endogenous, ectopic MITF-triggered tyrosinase gene in
      U2-OS cells. The dominant negative construct also strongly repressed the activity
      of a hyperactive MITF-Vp16 chimera. Importantly, deletion of both activation
      domains was necessary to eliminate the residual transcription activity observed
      when only the N-terminal domain was removed and to achieve the repressive effect
      in human melanoma cells. If the activity of MITF plays a role in the long-term
      survival of malignant melanocytes, overexpression of a strong dominant negative
      MITF mutant might be a useful strategy to suppress its transactivation function.

PMID- 14717846
TI  - Morphology of cultured human epidermal melanocytes observed by atomic force
      microscopy.
AB  - The objective of this study was to image the surface structure of cultured human
      epidermal melanocytes using atomic force microscopy (AFM). Epidermis obtained
      from human foreskins was treated with 0.5% dispase. Cell suspensions of the
      epidermis were prepared and seeded in six-well plates, in which sheets of mica
      had been placed. Samples for AFM were fixed on mica and scanning AFM images were
      captured by contacting and tapping modes operated under normal atmospheric
      pressure and temperature. Human epidermal melanocytes exhibited rounded, oval,
      triangular or quadrangular perikarya from which eight to 10 thick dendrites
      arose. These dendrites first bifurcated near the soma and then divided profusely
      into daughter branches, which spread out in all directions. We observed string
      like long thin projections, growth cones and shorter thicker projections, which
      arose from the dendritic shafts, in which groups of melanosomes were arrayed. In
      addition to such structures, the most striking feature was the presence of
      filopodia arising from the melanocyte dendrite tips and the melanocyte cell body,
      many of which contained melanosomes. The termini of dendrites formed unbranched
      terminal protrusions (approximately 1,500-2,000 nm wide) consisting of two to
      three melanosomes wrapped in an arc, with their filopodia extending outwards. The
      tips of these structures also appeared to be squeezed and finally pinched off by
      the melanocyte to form a pouch filled with numerous melanosomes. We conclude that
      secondary and tertiary branches and subordinate branches might take part in
      transferring melanosomes into keratinocytes in addition to the transfer through
      the tips of the dendritic shafts. The melanin granules were expelled by
      exocytosis.

PMID- 14717847
TI  - Quercetin enhances melanogenesis by increasing the activity and synthesis of
      tyrosinase in human melanoma cells and in normal human melanocytes.
AB  - Quercetin (3,3',4',5,7-pentahydroxyflavone) is a diphenyl propanoid widely
      distributed in edible plants. In this study, we examined the effect of quercetin
      on melanogenesis in human HMVII melanoma cells and in normal human epidermal
      melanocytes (NHEM) in the absence of ultraviolet radiation. Upon the addition of
      quercetin to the culture medium, the melanin content in melanoma cells (HMVII)
      increased remarkably in time- and dose-dependent manners. In addition, quercetin
      induced melanogenesis in cultured NHEM. As compared with controls, melanin
      content was increased about sevenfold by treatment with 20 microM (HMVII) or 1
      microM (NHEM) quercetin for 7 d. Tyrosinase activity was also increased, to 61.8
      fold higher than the control. The expression of tyrosinase protein was slightly
      increased by the addition of quercetin. However, quercetin did not affect the
      expression of tyrosinase mRNA. Tyrosinase activation by quercetin was blocked by
      actinomycin-D or by cycloheximide demonstrating that its actions in stimulating
      melanogenesis may involve both transcriptional and translational events.
      Tyrosinase activity was increased dramatically whereas the level of melanogenic
      inhibitor was remarkably decreased following quercetin treatment. Taken together,
      these results demonstrate that in human melanoma cells and in NHEM, quercetin
      stimulates melanogenesis by increasing tyrosinase activity and decreasing other
      factors such as melanogenic inhibitors.

PMID- 14717848
TI  - During human melanoma progression AP-1 binding pairs are altered with loss of c
      Jun in vitro.
AB  - We demonstrated previously that c-Jun, JunB and c-Fos RNA were dysregulated in
      metastatic melanoma cells compared with normal human melanocytes. The purpose of
      this study was to evaluate the distribution in composition of AP-1 dimers in
      human melanoma pathogenesis. We investigated AP-1 dimer pairing in radial growth
      phase-like (RGP) (w3211) and vertical growth phase-like (VGP) (w1205) human
      melanoma cells and metastatic cell lines (cloned from patients, c83-2c, c81-46A,
      A375, respectively) compared with melanocytes using electrophoretic mobility
      shift assay (EMSA), Western blot and transfection analyses. There are progressive
      variations in AP-1 composition in different melanoma cell lines compared with
      normal melanocytes, in which c-Jun, JunD and FosB were involved in AP-1
      complexes. In w3211, c-Jun, JunD and Fra-1 were involved in AP-1 binding, while
      in w1205, overall AP-1 binding activity was decreased significantly and
      supershift binding was detected only with JunD antibodies. In metastatic c81-46A
      and A375 cells, only JunD was involved in AP-1 binding activity, but in a third
      (c83-2c) c-Jun, JunD and Fra-1 were present. Western blot evaluation detected c
      Jun in melanocytes and w3211, but this component was decreased significantly or
      was not detectable in w1205, c81-46A and A375 cells. In contrast, JunD protein
      was elevated in c81-46A and c83-2c cells compared with melanocytes and RGP and
      VGP cell lines. Normal melanocytes and c83-2c cells (which have c-Jun involved in
      AP-1 binding), transfected with c-Jun antisense and treated with cisplatin,
      showed higher viability compared with untransfected cells, while in c81-46A cells
      (in which only JunD is detectable) no change in cell viability was observed
      following treatment with cisplatin and c-jun antisense transfection. A dominant
      negative c-Jun mutant (TAM67) significantly increased the soft agar colony
      formation of w3211 and c83-2c cells. These results suggest that components of AP
      1, especially c-Jun, may offer a new target for the prevention or treatment of
      human melanoma progression.

PMID- 14717849
TI  - Association of angiotensin converting enzyme gene I/D polymorphism of vitiligo in
      Korean population.
AB  - Vitiligo (leukoderma) is an acquired idiopathic hypomelanotic disorder
      characterized by the circumscribed depigmented patches. Vitiligo is a polygenic
      disease. The exact pathogenesis is not yet known. The angiotensin converting
      enzyme (ACE) gene was selected as a candidate gene as ACE plays an important role
      in the physiology of the vasculature, blood pressure and inflammation, and its
      relationship with various diseases, including autoimmune diseases, has been
      widely investigated. The I/D polymorphism of ACE gene in vitiligo patients has
      not been reported. In this study, we investigated ACE gene polymorphism in 120
      vitiligo patients and in 429 healthy volunteers in Korea. The ACE gene genotype
      distribution (P = 0.032) and allele frequency (P = 0.012) were significantly
      different between vitiligo patients and healthy controls. This study suggests
      that the ACE gene polymorphism has a strong association with the development of
      vitiligo in Korean patients.

PMID- 14717850
TI  - Comparison of long-term survival of pigmented epidermal reconstructs cultured in
      vitro vs. xenografted on nude mice.
AB  - Epidermal reconstructs incorporating pigment cells have been used in vitro over
      the last decade to study the physiology of the epidermal melanin unit. However,
      the major limitation of this technology is the duration of the assays, which need
      to be completed within 2-3 weeks to obviate the problem of epidermal senescence
      and excessive terminal differentiation. This becomes a major problem for studying
      long-term biological phenomena in photoprotection and epidermal skin cancers. We
      report here a simplified surgical technique in immunotolerant mice allowing long
      term studies. The creation of a vascularized mouse skin flap is the key point of
      the surgical procedure. Long-term pigmentation of the xenografts seemed
      macroscopically successful, but surprisingly microscopy at 11 and 16 weeks
      postgrafting showed mostly dermal pigment aggregates and rare Melan-A positive
      dermal and epidermal pigment cells. In the same reconstructs maintained in vitro,
      dermal pigment and dermal pigment cells were never noted. It could be speculated
      that in our model, the colonization of the xenografted dead human dermis by
      murine cells influences melanocyte survival.

PMID- 14717852
TI  - Periodontal diagnoses and classification of periodontal diseases.

PMID- 14717853
TI  - The complete periodontal examination.

PMID- 14717854
TI  - Imaging methods in periodontology.

PMID- 14717855
TI  - Microbiological diagnostic testing in the treatment of periodontal diseases.
AB  - A variety of microbiological diagnostic tests are available for clinicians to use
      for evaluation of patients with periodontal disease. Each one has its own unique
      set of advantages and disadvantages, and probably the most useful information for
      the clinician can be obtained using a combination of the various analytic
      methods. The tests appear to have their greatest utility when used on patients
      with chronic or aggressive periodontitis who do not respond favorable to
      conventional mechanical therapy. The major limitation of all microbiological
      tests is that the information obtained is relevant to the site sampled, and may
      not be representative of the microflora of the entire dentition. However, since
      it is often only specific sites that do not respond to initial therapy, knowing
      the constituents of the microflora that populate these sites is clinically
      relevant.

PMID- 14717856
TI  - Analysis of host responses and risk for disease progression.

PMID- 14717857
TI  - Laboratory testing of patients with systemic conditions in periodontal practice.

PMID- 14717858
TI  - Analysis of gingival crevice fluid and risk of progression of periodontitis.

PMID- 14717859
TI  - Risk assessment in clinical practice.

PMID- 14717860
TI  - Detection of localized tooth-related factors that predispose to periodontal
      infections.
AB  - The primary goal of periodontal therapy is to produce an environment that is
      conducive to oral health. This is achieved by eliminating the subgingival
      infection and implementing supragingival plaque control measures designed to
      prevent the re-colonization of the sulcus. Local etiologic factors, as described
      above, my prevent the removal of subgingival plaque, and may even contribute to
      destruction of the periodontal tissues. Thus, it is crucial to be able to
      recognize and, when possible, eliminate any plaque-retentive factor that could
      contribute to disease progression. Iatrogenic factors such as subgingival
      margins, restorative overhangs, overcontoured restorations and unpolished
      surfaces can be altered. Similarly, cervical enamel projections, enamel pearls
      and, in certain instances, palatal grooves can be removed or recontoured to
      enable the patient to access the area for good plaque control. There are some
      things that we cannot alter. Anatomic anomalies, particularly in posterior teeth,
      cannot be changed. However, awareness of potential anatomic variations and early
      detection of them may be able to prevent future attachment loss.

PMID- 14717861
TI  - Occlusal analysis, diagnosis and management in the practice of periodontics.

PMID- 14717862
TI  - Diagnosis, prognosis and decision-making in the treatment of combined periodontal
      endodontic lesions.

PMID- 14717863
TI  - Diagnosis of acute periodontal lesions.

PMID- 14717864
TI  - Diagnosis of periodontal manifestations of systemic diseases.
AB  - Many systemic diseases can mimic periodontitis or gingivitis. These include many
      immunologic, infectious, neoplastic and metabolic disorders. In comparison with
      periodontitis and gingivitis, these disorders are considerable less common.
      However, since their diagnosis and management differ, a high index of suspicion
      is frequently needed when confronted a patient presenting with gingival or
      periodontal disease. This chapter has reviewed a number of systemic conditions
      that may mimic clinically both gingivitis and chronic periodontitis and has
      focused on the features that may assist the clinician in making the diagnosis and
      providing specific therapies.

PMID- 14717865
TI  - Clinical evaluation of dental implant treatment.

PMID- 14717868
TI  - Airway structure, function and development in health and disease.
AB  - Until they are fully mature, the airways are highly susceptible to damage.
      Factors that may contribute to vulnerability of immature airways and the
      occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates include
      decreased contractility of smooth muscles of the airway, which leads to
      generation of lower forces, and immaturity of airway cartilage, leading to
      increased compressibility of developing airways. Mechanical ventilation has
      little effect on adult airways, but affects the dimensions and mechanical
      properties of preterm and newborn airways. Techniques for clinical evaluation of
      airway function include: (i). measurements of airway function during tidal
      breathing (airway resistance and reactivity are significantly elevated in infants
      with BPD); (ii). forced expiratory flow measurements [small-airway obstruction in
      infants with BPD is indicated by markedly reduced maximal volume measurements
      (Vmax)]; (iii). radiography procedures (plain radiographs, fluoroscopy, computed
      tomography and virtual bronchoscopy); and (iv). endoscopy procedures (rigid or
      flexible bronchoscopy, with or without measurement of oesophageal pressure).
      Imaging has demonstrated an excessively decreased airway cross-sectional area
      during exhalation in infants with BPD and acquired tracheomegaly in very preterm
      infants who had received mechanical ventilatory support. To further advance our
      understanding of how the airways develop, and to design less damaging protocols
      for mechanical ventilation in preterm neonates, basic laboratory studies of
      airway ultrastructure need to be performed and the results correlated with
      clinical pulmonary function studies.

PMID- 14717869
TI  - Liquid ventilation: an adjunct for respiratory management.
AB  - Although significant advances in respiratory care have reduced mortality of
      patients with respiratory failure, morbidity persists, often resulting from
      iatrogenic mechanisms. Mechanical ventilation with gas has been shown to initiate
      as well as exacerbate underlying lung injury, resulting in progressive structural
      damage and release of inflammatory mediators within the lung. Alternative means
      to support pulmonary gas exchange while preserving lung structure and function
      are therefore required. Perfluorochemical (PFC) liquids are currently used
      clinically in a number of ways, such as intravascular PFC emulsions for volume
      expansion/oxygen carrying/angiography and intracavitary neat PFC liquid for image
      contrast enhancement or vitreous fluid replacement. As a novel approach to
      replace gas as the respiratory medium, liquid assisted ventilation (LAV) with PFC
      liquids has been investigated as an alternative respiratory modality for over 30
      years. Currently, there are several theoretical and practical applications of LAV
      in the immature or mature lung at risk for acute respiratory distress and injury
      associated with mechanical ventilation.

PMID- 14717870
TI  - Teaching consultants airway management skills.
AB  - Airway management skills are integral to the practice of anaesthesiology and also
      to the practice of emergency medicine and allied health professions such as
      respiratory care, emergency medical technology, and emergency and critical care
      nursing. The basic information to be taught is the same but the level of detail
      will vary depending on the audience. The learning process usually involves
      progression from didactic lessons to skills training on inanimate models to
      supervised clinical practice. Modalities that may be used for skills training
      include cadavers, recently dead patients, videotapes, mannequins, simulators and
      virtual reality trainers. To maintain knowledge and skills, review and possible
      retraining should be conducted on an approximately annual basis.

PMID- 14717871
TI  - Simulators and difficult airway management skills.
AB  - Although difficult airway management remains one of the leading factors in
      anaesthetic deaths, there have been tremendous advances in the field in the last
      few decades. The question is, are advanced airway management skills being taught
      and used? Of the numerous training tools available, simulators have the
      advantages of providing whole-task learning with the potential to change
      behaviour and, when applied to large groups of trainees, the possibility of
      achieving standardized application of the safest practices for a range of
      scenarios limited only by the creativity of the program designers. Partial-task
      trainers include computer-based software programs and simulators. Full-scale
      simulators include a variety of products from several manufacturers. To take full
      advantage of simulators as educational tools, curricula should be designed around
      a set of educational objectives that address the objectives of learning in all
      three skill domains (cognitive, psychomotor, and affective). Simulation
      experiences using partial-task or whole-task trainers should be coupled whenever
      feasible with a structured clinical experience in airway management. This can
      best be achieved through a dedicated airway management rotation. Monitored
      procedure logs may also be used. Whether using a simulator or in a clinical
      rotation, experiences should be graded, for example, gaining experience in an
      adult population before gaining experience in paediatrics and in each population
      mastering airway management skills for common scenarios before advancing to more
      complicated techniques such as fibreoptic bronchoscopy.

PMID- 14717872
TI  - The future of the cuffed endotracheal tube.
AB  - It has been traditionally taught that only uncuffed endotracheal tubes (ETTs)
      should be used for intubation in children younger than 8, or even 10, years old.
      However, recent literature suggests that the advantages of using uncuffed ETTs in
      children may be just another myth of paediatric anaesthesia. Using an uncuffed
      ETT does allow a tube of larger internal diameter to be used, minimizing
      resistance to airflow and the work of breathing in the patient who is breathing
      spontaneously. However, this advantage does not hold for ventilated patients, for
      whom ventilator settings can be adjusted to provide optimal airflow. Longer
      duration of intubation and a poorly fitted ETT are risk factors for mucosal
      damage, whether the ETT is cuffed or uncuffed. Furthermore, a properly sized,
      positioned, and inflated modern (low-pressure, high-volume) cuffed ETT can offer
      many advantages over an uncuffed ETT, including greater ease of intubation,
      better control of air leakage, lower rate and better control of flow of
      anaesthetic gases, and decreased risk of aspiration and infection.

PMID- 14717873
TI  - Cricoid pressure: indications and complications.
AB  - Cricoid pressure to occlude the upper end of the oesophagus, also called the
      Sellick manoeuvre, may be used to decrease the risk of pulmonary aspiration of
      gastric contents during intubation for rapid induction of anaesthesia. Effective
      and safe use of the technique requires training and experience. Cricoid pressure
      is contraindicated in patients with suspected cricotracheal injury, active
      vomiting, or unstable cervical spine injuries. The technique may be particularly
      difficult in patients with a history of difficult intubation. The recommended
      pressure to prevent gastric reflux is between 30 and 40 Newtons (N, equivalent to
      3-4 kg), but pressures greater than 20 N cause pain and retching in awake
      patients and a pressure of 40 N can distort the larynx and complicate intubation.
      The recommended procedure is, therefore, to induce anaesthesia and apply a
      pressure of about 30 N, either manually or with the cricoid yoke, to facilitate
      intubation. Reported complications of cricoid pressure during intubation include
      oesophageal rupture and exacerbation of unsuspected airway injuries.

PMID- 14717874
TI  - Prenatal diagnosis and intrapartum management of neck masses causing airway
      obstruction.

PMID- 14717875
TI  - The airway in patients with craniofacial abnormalities.
AB  - Airway management for patients with craniofacial disorders poses many challenges.
      The anaesthesiologist must be familiar with the normal bony and soft-tissue
      anatomy in the airway and how anatomy is altered by various congenital disorders.
      Specific areas to assess include the oral cavity, anterior mandibular space,
      maxilla, temporomandibular joint and vertebral column. Congenital conditions that
      may alter normal anatomy and therefore anaesthetic management include cleft lip
      and palate with or without Pierre Robin syndrome, craniofacial dysostosis,
      mandibulofacial dysostosis/Treacher Collins syndrome, hemifacial microsomia,
      Klippel-Feil syndrome, Beckwith-Wiedemann syndrome, trisomy 21/Down's syndrome,
      Freeman-Sheldon/whistling face syndrome/craniocarpotarsal dysplasia,
      fibrodysplasia ossificans progressiva, mucopolysaccharidosis and vascular
      malformations.

PMID- 14717876
TI  - Cardiovascular causes of airway compression.
AB  - Compression of the paediatric airway is a relatively common and often
      unrecognized complication of congenital cardiac and aortic arch anomalies. Airway
      obstruction may be the result of an anomalous relationship between the
      tracheobronchial tree and vascular structures (producing a vascular ring) or the
      result of extrinsic compression caused by dilated pulmonary arteries, left atrial
      enlargement, massive cardiomegaly, or intraluminal bronchial obstruction. A high
      index of suspicion of mechanical airway compression should be maintained in
      infants and children with recurrent respiratory difficulties, stridor, wheezing,
      dysphagia, or apnoea unexplained by other causes. Prompt diagnosis is required to
      avoid death and minimize airway damage. In addition to plain chest radiography
      and echocardiography, diagnostic investigations may consist of barium
      oesophagography, magnetic resonance imaging (MRI), computed tomography, cardiac
      catheterization and bronchoscopy. The most important recent advance is MRI, which
      can produce high quality three-dimensional reconstruction of all anatomic
      elements allowing for precise anatomic delineation and improved surgical
      planning. Anaesthetic technique will depend on the type of vascular ring and the
      presence of any congenital heart disease or intrinsic lesions of the
      tracheobronchial tree. Vascular rings may be repaired through a conventional
      posterolateral thoracotomy, or utilizing video-assisted thoracoscopic surgery
      (VATS) or robotic endoscopic surgery. Persistent airway obstruction following
      surgical repair may be due to residual compression, secondary airway wall
      instability (malacia), or intrinsic lesions of the airway. Simultaneous repair of
      cardiac defects and vascular tracheobronchial compression carries a higher risk
      of morbidity and mortality.

PMID- 14717877
TI  - Chronic upper airway obstruction and cardiac dysfunction: anatomy,
      pathophysiology and anesthetic implications.
AB  - The causes of obstruction to airflow in the pediatric upper airway include
      craniofacial disorders, subglottic stenosis, choanal atresia, syndromes
      associated with neuromuscular weakness, and the most common, hypertrophy of the
      tonsils and adenoids. Abnormal breathing can adversely affect craniofacial
      growth, and abnormal craniofacial development can promote upper airway
      obstruction. Chronic upper airway obstruction often presents with evidence of
      obstructive sleep apnea syndrome; in severe cases these children also present
      with pulmonary hypertension and cor pulmonale. The development of pulmonary
      hypertension and right heart dysfunction from chronic upper airway obstruction is
      complex. Hypoxemia and hypercarbia-induced respiratory acidosis are potent
      mediators of pulmonary vasoconstriction that can lead to reversible and
      irreversible chronic changes in the pulmonary vasculature. It is likely that
      production of various neurohumoral factors in response to hypoxemia and
      respiratory distress may further promote pulmonary hypertension, right
      ventricular dysfunction, and consequent impairment of systemic cardiac output.
      The anesthetic considerations for children undergoing adenotonsillectomy for
      chronic airway obstruction are significant. These children are at high risk for
      complications such as laryngospasm, desaturation, stimulation of pulmonary
      hypertension and cardiac dysfunction, pulmonary edema, postoperative upper airway
      obstruction, and respiratory arrest. Because of underlying condition(s) (facial
      abnormalities, neuromuscular disease, etc.), successful adenotonsillar surgery
      may not improve upper airway obstruction significantly, especially in the
      immediate postoperative period when edema, bleeding and the effects of
      anesthetics and analgesics are present.

PMID- 14717878
TI  - Rigid bronchoscopy for foreign body removal: anaesthesia and ventilation.
AB  - Foreign body aspiration is a leading cause of death in children 1-3 years old,
      although mortality is low for children who reach the hospital. Presenting
      symptoms of an inhaled foreign body depends on time since aspiration. Immediately
      after inhalation the child starts to cough, wheeze, or have laboured breathing.
      If the early signs are missed, the child usually presents with fever and other
      signs and symptoms of chest infection. A plain chest X-ray has relatively low
      sensitivity and specificity for inhaled foreign body. The gold standard for
      diagnosis and management of this condition is rigid open tube bronchoscopy under
      general anaesthesia. For late presentations, time should be taken to fast the
      child and complete a thorough evaluation before bronchoscopy. The procedure
      should be performed in a well-equipped room with at least two anaesthesiologists,
      one with paediatric experience, in attendance. Most experienced
      anaesthesiologists prefer inhalational rather than intravenous induction of
      anaesthesia and a ventilating bronchoscope rather than intubation. Equally good
      results have been reported with spontaneous ventilation or positive pressure
      ventilation; jet ventilation is not advocated for foreign body removal in
      children.

PMID- 14717879
TI  - Microlaryngoscopy-airway management with anaesthetic techniques for CO(2) laser.
AB  - Carbon dioxide laser microlaryngoscopy requires planning and cooperation of both
      the anaesthesiologist and surgeon. While there are potentially significant
      complications, such as fire and difficulty ventilating the patient, laser
      microlaryngoscopy techniques provide the benefit of allowing for precise
      management of a wide range of upper airway conditions. Laryngoscopy and
      bronchoscopy require that the surgeon and anaesthesiologist cooperate in order to
      maximize exposure for the surgeon and allow for adequate ventilation of the
      patient. The type of airway the anaesthesiologist may use is dictated by whether
      access is needed to the hypopharynx, supraglottis, larynx, or subglottis. When
      the carbon dioxide laser is used for airway surgery, ventilation techniques that
      may be used include jet ventilation (subglottic or supraglottic) and intermittent
      or continuous endotracheal intubation, with a variety of tubes. The major
      complication to be avoided is airway fire. Each technique has advantages and
      disadvantages for avoiding fire and providing adequate ventilation. Fire is not a
      concern when the carbon dioxide laser bronchoscope is used, but the humidifier
      must be eliminated from the anaesthesia circuit to avoid vapour obstructing the
      bronchoscope coupler.

PMID- 14717880
TI  - Anaesthetic management for the child with a mediastinal mass.
AB  - Administering anaesthesia to a child with an anterior mediastinal mass may lead
      to respiratory or circulatory collapse, even in those without symptoms.
      Institutions should have algorithms to manage children with mediastinal masses.
      Preoperative evaluations should include computed tomography, echocardiography and
      flow-volume studies. Anaesthesia may be induced with inhalation agents and
      maintained with spontaneous respiration via facemask or laryngeal mask airway.
      Alternatively, positive-pressure ventilation may be used, including tracheal
      intubation without muscle relaxants. Rigid bronchoscopy may be life-saving in the
      event of tracheal or bronchial collapse under anaesthesia.

PMID- 14717881
TI  - Single-lung ventilation in infants and children.
AB  - During the past decade, the use of video-assisted thoracoscopic surgery (VATS)
      has dramatically increased in children as well as adults. Although VATS can be
      performed while both lungs are being ventilated, single-lung ventilation (SLV) is
      desirable during VATS. In addition, anaesthesiologists are performing (and
      paediatric surgeons are requesting) SLV more frequently for open thoracotomies in
      infants and children.

PMID- 14717882
TI  - Trauma of the larynx and craniofacial structures: airway implications.
AB  - Laryngeal trauma in children is potentially life-threatening. An organized
      approach by all who care for these children in an emergency situation is
      essential. Prompt recognition and treatment of such injuries will minimize the
      risk of long-term complications that would require multiple operative procedures
      and prolonged rehabilitation.

PMID- 14717883
TI  - Prevention and management of complications of airway surgery in children.
AB  - Preventing and managing complications of airway surgery in children requires
      proactive attention to both surgical and anaesthetic aspects of the planned
      procedure. Preoperative evaluation should include a thorough physical examination
      and, especially in children with multiple congenital anomalies, flexible
      fibreoptic nasopharyngolaryngoscopy, direct laryngoscopy and rigid or flexible
      bronchoscopy. The goal is to identify dynamic abnormalities such as
      laryngomalacia or vocal cord paralysis, tracheal or bronchial lesions, gastro
      oesophageal reflux disease (GORD), aspiration, laryngotracheal stenosis, totally
      obstructing tracheostomy-associated granulation tissue and Noonan syndrome
      preoperatively, and then to plan surgical management to achieve the best possible
      outcome for each patient.

PMID- 14717884
TI  - Genetic diversity and structure of urban populations of Pieris butterflies
      assessed using amplified fragment length polymorphism.
AB  - Conservation programs in urban ecosystems need to determine the genetic
      background in populations of urban dwellers. We examined the genetic diversity
      and structure of Pieris rapae and P. melete using AFLP markers, and compared them
      between species and between urban and rural environments. As a result: (i). in
      both species, there was no reduction in genetic diversity within urban
      populations by direct comparison of diversity measurements, although the analysis
      of molecular variance suggested significant reductions in the variance within
      seasonal subpopulations in urban populations; (ii). P. rapae retained greater
      genetic diversity within species and populations; (iii). populations of both
      species showed significant genetic differentiation, and P. melete was more
      strongly subdivided; (iv). in both species, geographically close populations did
      not cluster with one another in the upgma analysis; (v). there was no genetic
      isolation due to geographical distance in either species; (vi). the genetic
      composition of seasonal subpopulations differed in urban populations of both
      species, and the genetic distances among subpopulations were correlated with
      seasonal differences in P. rapae and with temporal differences in P. melete.
      These results indicate that the genetic diversity in urban populations of both
      species was reduced at times, but was maintained by dispersal from genetically
      differentiated populations. Differences in the ability and mode of dispersal in
      the two species may be reflected in the degree of population subdivision and
      patterns of seasonal change in the genetic composition.

PMID- 14717885
TI  - Limited effect of anthropogenic habitat fragmentation on molecular diversity in a
      rain forest skink, Gnypetoscincus queenslandiae.
AB  - To examine the effects of recent habitat fragmentation, we assayed genetic
      diversity in a rain forest endemic lizard, the prickly forest skink
      (Gnypetoscincus queenslandiae), from seven forest fragments and five sites in
      continuous forest on the Atherton tableland of northeastern Queensland,
      Australia. The rain forest in this region was fragmented by logging and clearing
      for dairy farms in the early 1900s and most forest fragments studied have been
      isolated for 50-80 years or nine to 12 skink generations. We genotyped 411
      individuals at nine microsatellite DNA loci and found fewer alleles per locus in
      prickly forest skinks from small rain forest fragments and a lower ratio of
      allele number to allele size range in forest fragments than in continuous forest,
      indicative of a decrease in effective population size. In contrast, and as
      expected for populations with small neighbourhood sizes, neither heterozygosity
      nor variance in allele size differed between fragments and sites in continuous
      forests. Considering measures of among population differentiation, there was no
      increase in FST among fragments and a significant isolation by distance pattern
      was identified across all 12 sites. However, the relationship between genetic
      (FST) and geographical distance was significantly stronger for continuous forest
      sites than for fragments, consistent with disruption of gene flow among the
      latter. The observed changes in genetic diversity within and among populations
      are small, but in the direction predicted by the theory of genetic erosion in
      recently fragmented populations. The results also illustrate the inherent
      difficulty in detecting genetic consequences of recent habitat fragmentation,
      even in genetically variable species, and especially when effective population
      size and dispersal rates are low.

PMID- 14717886
TI  - Historical data refute recent range contraction as cause of low genetic diversity
      in isolated frog populations.
AB  - This study tested whether low genetic diversity in remnant populations of a
      declining amphibian is best explained by recent bottlenecks or by a history of
      being peripheral. We compared diversity from eight microsatellite loci in
      historical and extant populations from the interior and former periphery of the
      species' range. We found that historic peripheral populations already had reduced
      levels of genetic variation before the range contraction. Therefore, low
      diversity in remnants could not be ascribed to recent range contractions. This
      study shows that a common conservation strategy for rescuing genetically
      depauperate populations, artificial gene flow, may often be unwarranted and
      detrimental to evolutionarily important peripheral populations.

PMID- 14717887
TI  - Founding events influence genetic population structure of sockeye salmon
      (Oncorhynchus nerka) in Lake Clark, Alaska.
AB  - Bottlenecks can have lasting effects on genetic population structure that obscure
      patterns of contemporary gene flow and drift. Sockeye salmon are vulnerable to
      bottleneck effects because they are a highly structured species with excellent
      colonizing abilities and often occupy geologically young habitats. We describe
      genetic divergence among and genetic variation within spawning populations of
      sockeye salmon throughout the Lake Clark area of Alaska. Fin tissue was collected
      from sockeye salmon representing 15 spawning populations of Lake Clark, Six-mile
      Lake, and Lake Iliamna. Allele frequencies differed significantly at 11
      microsatellite loci in 96 of 105 pairwise population comparisons. Pairwise
      estimates of FST ranged from zero to 0.089. Six-mile Lake and Lake Clark
      populations have historically been grouped together for management purposes and
      are geographically proximate. However, Six-mile Lake populations are genetically
      similar to Lake Iliamna populations and are divergent from Lake Clark
      populations. The reduced allelic diversity and strong divergence of Lake Clark
      populations relative to Six-mile Lake and Lake Iliamna populations suggest a
      bottleneck associated with the colonization of Lake Clark by sockeye salmon.
      Geographic distance and spawning habitat differences apparently do not contribute
      to isolation and divergence among populations. However, temporal isolation based
      on spawning time and founder effects associated with ongoing glacial retreat and
      colonization of new spawning habitats contribute to the genetic population
      structure of Lake Clark sockeye salmon. Nonequilibrium conditions and the strong
      influence of genetic drift caution against using estimates of divergence to
      estimate gene flow among populations of Lake Clark sockeye salmon.

PMID- 14717888
TI  - Historical and contemporary multilocus population structure of Ascochyta rabiei
      (teleomorph: Didymella rabiei) in the Pacific Northwest of the United States.
AB  - The historical and contemporary population genetic structure of the chickpea
      Ascochyta blight pathogen, Ascochyta rabiei (teleomorph: Didymella rabiei), was
      determined in the US Pacific Northwest (PNW) using 17 putative AFLP loci, four
      genetically characterized, sequence-tagged microsatellite loci (STMS) and the
      mating type locus (MAT). A single multilocus genotype of A. rabiei (MAT1-1) was
      detected in 1983, which represented the first recorded appearance of Ascochyta
      blight of chickpea in the PNW. During the following year many additional alleles,
      including the other mating type allele (MAT1-2), were detected. By 1987, all
      alleles currently found in the PNW had been introduced. Highly significant
      genetic differentiation was detected among contemporary subpopulations from
      different hosts and geographical locations indicating restricted gene flow and/or
      genetic drift occurring within and among subpopulations and possible selection by
      host cultivar. Two distinct populations were inferred with high posterior
      probability which correlated to host of origin and date of sample using Bayesian
      model-based population structure analyses of multilocus genotypes. Allele
      frequencies, genotype distributions and population assignment probabilities were
      significantly different between the historical and contemporary samples of
      isolates and between isolates sampled from a resistance screening nursery and
      those sampled from commercial chickpea fields. A random mating model could not be
      rejected in any subpopulation, indicating the importance of the sexual stage of
      the fungus both as a source of primary inoculum for Ascochyta blight epidemics
      and potentially adaptive genotypic diversity.

PMID- 14717889
TI  - Effects of habitat fragmentation on the genetic structure of the monophagous
      butterfly Polyommatus coridon along its northern range margin.
AB  - Population genetic patterns of species at their range margin have important
      implications for species conservation. We performed allozyme electrophoresis of
      19 loci to investigate patterns of the genetic structure of 17 populations (538
      individuals) of the butterfly Polyommatus coridon, a monophagous habitat
      specialist with a patchy distribution. The butterfly and its larval food plant
      Hippocrepis comosa reach their northern distribution margin in the study region
      (southern Lower Saxony, Germany). Butterfly population size increased with host
      plant population size. The genetic differentiation between populations was low
      but significant (FST = 0.013). No isolation-by-distance was found. Hierarchical F
      statistics revealed significant differentiation between a western and an eastern
      subregion, separated by a river valley. The combination of genetic and ecological
      data sets revealed that the expected heterozygosity (mean: 18.5%) decreased with
      increasing distance to the nearest P. coridon population. The population size of
      P. coridon and the size of larval food plant population had no effect on the
      genetic diversity. The genetic diversity of edge populations of P. coridon was
      reduced compared to populations from the centre of its distribution. This might
      be explained by (i). an increasing habitat fragmentation towards the edge of the
      distribution range and/or (ii). a general reduction of genetic variability
      towards the northern edge of its distribution.

PMID- 14717890
TI  - Unreliable mtDNA data due to nuclear insertions: a cautionary tale from analysis
      of humans and other great apes.
AB  - Analysis of mitochondrial DNA sequence variation has been used extensively to
      study the evolutionary relationships of individuals and populations, both within
      and across species. So ubiquitous and easily acquired are mtDNA data that it has
      been suggested that such data could serve as a taxonomic 'barcode' for an
      objective species classification scheme. However, there are technical pitfalls
      associated with the acquisition of mtDNA data. One problem is the presence of
      translocated pieces of mtDNA in the nuclear genome of many taxa that may be
      mistaken for authentic organellar mtDNA. We assessed the extent to which such
      'numt' sequences may pose an overlooked problem in analyses of mtDNA from humans
      and apes. Using long-range polymerase chain reaction (PCR), we generated
      necessarily authentic mtDNA sequences for comparison with sequences obtained
      using typical methods for a segment of the mtDNA control region in humans,
      chimpanzees, bonobos, gorillas and orangutans. Results revealed that gorillas are
      notable for having such a variety of numt sequences bearing high similarity to
      authentic mtDNA that any analysis of mtDNA using standard approaches is rendered
      impossible. Studies on humans, chimpanzees, bonobos or orangutans are apparently
      less problematic. One implication is that explicit measures need to be taken to
      authenticate mtDNA sequences in newly studied taxa or when any irregularities
      arise. Furthermore, some taxa may not be amenable to analysis of mtDNA variation
      at all.

PMID- 14717891
TI  - The population genetics of a biological control introduction: mitochondrial DNA
      and microsatellie variation in native and introduced populations of Aphidus ervi,
      a parisitoid wasp.
AB  - Introductions of biological control agents may cause bottlenecks in population
      size despite efforts to avoid them. We examined the population genetics of
      Aphidius ervi (Hymenoptera: Braconidae), a parasitoid that was introduced to
      North America from Western Europe in 1959 to control pea aphids. To explore the
      phylogeographical relationships of A. ervi we sequenced 1249 bp of mitochondrial
      DNA (mtDNA) from 27 individuals from the native range and 51 individuals from the
      introduced range. Most individuals from Western Europe, the Middle East and North
      America shared one of two common haplotypes, consistent with the known history of
      the introduction. However, some A. ervi from the Pacific Northwest have a
      haplotype that is most similar to haplotypes found in Japan, raising the
      possibility of a second accidental introduction. To examine population structure
      and assess whether a bottleneck occurred upon introduction to North America, we
      assayed variation at 5 microsatellite loci in 62 individuals from 2 native
      populations and 230 individuals from 6 introduced populations. Introduced samples
      had fewer rare alleles than native samples (F1,34 = 13.5, P = 0.0008), but
      heterozygosity did not differ significantly. These results suggest that a mild
      bottleneck occurred in spite of the introduction of over 1000 individuals. Using
      a hierarchical Bayesian approach, the founding population size was estimated to
      be 245 individuals. amova showed significant genetic differentiation between the
      European and North American samples, and a Bayesian assignment approach clustered
      individuals into four groups, with most European individuals in one group and
      most North American individuals in the other three. These results highlight that
      genetic changes are associated with founder events in rapidly growing natural
      populations, even when the founding population size is relatively large.

PMID- 14717892
TI  - Extensive chloroplast haplotype variation indicates Pleistocene hybridization and
      radiation of North American Arabis drummondii, A. x divaricarpa, and A.
      holboellii (Brassicaceae).
AB  - Arabis drummondii, A. holboellii and their hybrid A. x divaricarpa are widespread
      perennials of open habitats in North America. A phylogenetic analysis based on
      noncoding chloroplast DNA sequences (trnL intron and trnL/F intergenic spacer)
      resolved A. drummondii as a monophyletic taxon, but found A. holboellii to bear
      chloroplast haplotypes from highly diverged evolutionary lineages. This raised
      the question of a possible polyphyletic origin of A. holboellii. Arabis x
      divaricarpa was found to be of recent and polytopic origin, a result consistent
      with its presumed hybrid origin. One hundred and three chloroplast haplotypes
      were detected within 719 Arabis accessions investigated. The majority of
      chloroplast-types were estimated to have arisen prior to the Wisconsin
      glaciation. Phylogeographical analysis using nested clade analysis, suggested for
      A. holboellii (i). past fragmentation events, partitioning genetic variation in
      several instances between the Sierra Nevada, the Southern Rocky Mountains and the
      Colorado Plateau on the one hand and the Central to Northern Rockies of the
      United States and adjacent Cascades on the other; and for both parental species
      (ii). recolonization of major areas formerly covered by the Wisconsin glaciation
      by three haplotypes; and (iii). restricted gene flow indicating isolation by
      distance in areas south of the last glacial maximum. Arabis x divaricarpa is
      closely codistributed with its parental species and resampled their haplotypes.
      The highest genetic diversity was found in the Rocky Mountains from Idaho and
      Montana south to Utah and Colorado. This area was further hypothesized to have
      played a major role in the origin of both parental species and probably
      represented an important glacial refugium. However, evidence for glacial refugia
      was also found in arctic and boreal regions of Alaska and near the Great Lakes.
      In comparison to nuclear ribosomal internal transcribed spacer data, chloroplast
      DNA divergence was very high and evidently predated the origin of A. drummondii
      and possibly A. holboellii. Divergence of major chloroplast lineages dates back
      to the middle of the Pleistocene at least. Extensive hybridization is the most
      likely evolutionary factor working on A. holboellii to explain the revealed
      discrepancy in nuclear DNA and chloroplast DNA diversification.

PMID- 14717893
TI  - Phylogeography, genetic structure and diversity in the endangered bearded vulture
      (Gypaetus barbatus, L) as revealed by mitochondrial DNA.
AB  - Bearded vulture populations in the Western Palearctic have experienced a severe
      decline during the last two centuries that has led to the near extinction of the
      species in Europe. In this study we analyse the sequence variation at the
      mitochondrial control region throughout the species range to infer its recent
      evolutionary history and to evaluate the current genetic status of the species.
      This study became possible through the extensive use of museum specimens to study
      populations now extinct. Phylogenetic analysis revealed the existence of two
      divergent mitochondrial lineages, lineage A occurring mainly in Western European
      populations and lineage B in African, Eastern European and Central Asian
      populations. The relative frequencies of haplotypes belonging to each lineage in
      the different populations show a steep East-West clinal distribution with maximal
      mixture of the two lineages in the Alps and Greece populations. A genealogical
      signature for population growth was found for lineage B, but not for lineage A;
      futhermore the Clade B haplotypes in western populations and clade A haplo-types
      in eastern populations are recently derived, as revealed by their peripheral
      location in median-joining haplotype networks. This phylogeographical pattern
      suggests allopatric differentiation of the two lineages in separate Mediterranean
      and African or Asian glacial refugia, followed by range expansion from the latter
      leading to two secondary contact suture zones in Central Europe and North Africa.
      High levels of among-population differentiation were observed, although these
      were not correlated with geographical distance. Due to the marked genetic
      structure, extinction of Central European populations in the last century re
      sulted in the loss of a major portion of the genetic diversity of the species. We
      also found direct evidence for the effect of drift altering the genetic
      composition of the remnant Pyrenean population after the demographic bottleneck
      of the last century. Our results argue for the management of the species as a
      single population, given the apparent ecological exchangeability of extant
      stocks, and support the ongoing reintroduction of mixed ancestry birds in the
      Alps and planned reintroductions in Southern Spain.

PMID- 14717894
TI  - Current and historical patterns of drainage connectivity in eastern Australia
      inferred from population genetic structuring in a widespread freshwater fish
      Pseudomugil signifer (Pseudomugilidae).
AB  - Dispersal can play an important role in the genetic structuring of natural
      populations. In this regard, freshwater fishes often exhibit extensive population
      genetic subdivision and are ideal subjects for investigating current and
      historical patterns of connection and dissociation between drainages. We set out
      to generate a comprehensive molecular phylogeny for a widespread freshwater fish
      from eastern Australia, the Pacific blue-eye Pseudomugil signifer. Although
      movement via flood events may be important in the southern end of the species'
      range, genetic structuring revealed the importance of historical drainage
      connections and dissociations in mediating or disrupting dispersal. A dominant
      feature of our phylogeny is a split between northern and southern populations,
      which appears to be congruent with a biogeographical barrier recently implicated
      as important for the connectivity of freshwater organisms in eastern Australia.
      The extent of the split also has taxonomic implications consistent with
      suggestions that the Pacific blue-eye may represent more than a single species.

PMID- 14717895
TI  - Phylogeography of the common goby, Pomatoschistus microps, with particular
      emphasis on the colonization of the Mediterranean and the North Sea.
AB  - The phylogeographical patterns of a small marine fish, the common goby,
      Pomatoschistus microps, were assessed at 12 sites along the northeastern Atlantic
      coasts and the western Mediterranean Sea. A combination of two genetic markers
      was employed: cellulose acetate allozyme electrophoresis (CAGE) and sequence
      analysis of a 289 bp fragment of the mitochondrial locus cytochrome b. Both
      markers were congruent in revealing significant differences between samples
      (global FST = 0.247 for the allozymes and PhiST = 0.437 for the mitochondrial DNA
      data) and a pattern of isolation-by-distance. Phylogeographical analyses yielded
      a shallow branching structure with four groups. Three of those were confined to
      the Atlantic basin and showed a star-like pattern. The fourth group contained a
      central haplotype occurring at the edges of the species' distribution,
      accompanied by a few more rare variants, which were restricted to the
      Mediterranean Sea. A genetic break was observed around the British Isles, with
      distinct haplotypes dominating at either side of the English Channel. A
      significantly negative correlation between the degree of genetic diversity and
      latitude was recorded both for mitochondrial DNA (mtDNA) and allozymes in the
      Atlantic basin. Gene flow analysis suggested that recolonization of the North Sea
      and the coasts of western Scotland and Ireland may have taken place from a
      glacial refugium in the Southern Bight of the North Sea. These results are
      discussed in the perspective of possible postglacial migration routes of marine
      fish along the northeastern Atlantic coasts.

PMID- 14717896
TI  - High mate and site fidelity in cunningham's skinks (Egernia cunninghami) in
      natural and fragmented habitat.
AB  - While habitat alteration has considerable potential to disrupt important within
      population processes, such as mating and kin structure, via changed patterns of
      dispersal, this has rarely been tested. We are investigating the impact of
      anthropogenic habitat alteration on the population biology of the rock-dwelling
      Australian lizard Egernia cunninghami on the Central Tablelands of New South
      Wales, Australia, by comparing deforested and adjacent naturally vegetated areas.
      The novel analyses in this paper, and its companion, build on previous work by
      adding a new replicate site, more loci and more individuals. The additional
      microsatellite loci yield sufficient power for parentage analysis and the
      sociobiological inferences that flow from it. Genetic and capture-mark-recapture
      techniques were used to investigate mate and site fidelity and associated kin
      structure. Analyses of the mating system and philopatry using 10 microsatellite
      loci showed high levels of site fidelity by parents and their offspring in
      natural and deforested habitats. Parentage assignment revealed few individuals
      with multiple breeding partners within seasons and fidelity of pairs across two
      or more breeding seasons was typical. Despite reduced dispersal, increased group
      sizes and significant, dramatic increases in relatedness among individuals within
      rock outcrops in deforested areas, no significant differences between deforested
      and natural areas were evident in the degree of multiple mating or philopatry of
      breeding partners within and across seasons. With the exception that there was a
      significantly higher proportion of unmated males in the deforested area, the
      social and mating structure of this species has so far been surprisingly robust
      to substantial perturbation of dispersal and relatedness structure. Nonetheless,
      approximately 10-fold elevation of mean pairwise relatedness in the deforested
      areas has great potential to increase inbred matings, which is investigated in
      the companion paper.

PMID- 14717897
TI  - Colony genetic organization and colony fusion in the termite Reticulitermes
      flavipes as revealed by foraging patterns over time and space.
AB  - Temporal and spatial analyses are seldom utilized in the study of colony genetic
      structure, but they are potentially powerful methods which can yield novel
      insights into the mechanisms underlying variation in breeding systems. Here we
      present the results of a study which incorporated both of these dimensions in an
      examination of genetic structure of subterranean termites in the genus
      Reticulitermes (primarily R. flavipes). Most colonies of this species (70%) were
      simple families apparently headed by outbred primary reproductives, while most of
      the remaining (27% of the total) colonies contained low effective numbers of
      moderately inbred reproductives. Mapping the spatial distribution of colony
      foraging sites over time revealed that despite the high colony density, the
      absolute foraging boundaries of most R. flavipes colonies were persistent and
      exclusive of other conspecific colonies, which suggests that this species is more
      territorial than has been implied by laboratory studies of intraspecific
      aggression. Nevertheless, we found a single colony (3% of all colonies) which
      contained the offspring of more than two unrelated reproductives. Although other
      studies have also described subterranean termite colonies with a similarly
      complex genetic composition, we demonstrate here that such colonies can form
      under natural conditions via the fusion of whole colonies. This study underscores
      how repeated sampling from individual colonies over time and space can yield
      information about colony spatial and genetic structure that cannot be obtained
      from conventional analyses or sampling methods.

PMID- 14717898
TI  - Inbreeding avoidance in cunningham's skinks (Egernia cunninghami) in natural and
      fragmented habitat.
AB  - Habitat fragmentation/alteration has been proposed as a distinct process
      threatening the viability of populations of many organisms. One expression of its
      impact may be the disruption of core population processes such as inbreeding
      avoidance. Using the experimental design outlined in our companion paper, we
      report on the impact of habitat alteration (deforestation) on inbreeding in the
      rock-dwelling Australian lizard Egernia cunninghami. Ten microsatellite loci were
      used to calculate relatedness coefficients of potential and actual breeding
      pairs, and to examine mate-choice and heterozygosity. Despite significantly less
      dispersal and higher within-group relatedness between potential mates in
      deforested than in natural habitats, this did not result in significantly more
      inbred matings. Average relatedness amongst breeding pairs was low, with no
      significant difference between natural and fragmented populations in relatedness
      between breeding pairs, or individual heterozygosity. Active avoidance of close
      kin as mates was indicated by the substantially and significantly lower
      relatedness in actual breeding pairs than potential ones. These facts, and
      heterozygote excesses in all groups of immature lizards from both habitats, show
      that E. cunninghami maintained outbreeding in the face of increased accumulation
      of relatives.

PMID- 14717899
TI  - Behavioural structuring of relatedness in the spotted hyena (Crocuta crocuta)
      suggests direct fitness benefits of clan-level cooperation.
AB  - Spotted hyenas (Crocuta crocuta) are gregarious carnivores that live in
      multigenerational social groups, called clans, containing one to several
      matrilines. Members of multiple matrilines within a clan cooperate during
      dangerous interactions with inter- and intraspecific competitors. The evolution
      of cooperation may be influenced by relatedness between individuals, which in
      turn is influenced by reproductive skew and mate choice, dispersal and
      territorial behaviours. Behavioural data exist for spotted hyenas, but
      corresponding data on patterns of relatedness are unavailable; this lack of data
      makes it difficult to assess the relative importance of selection pressures
      favouring cooperative behaviour within and among groups. Therefore we conducted a
      longitudinal analysis of relatedness within a single large clan of spotted
      hyenas, as well as a cross-sectional analysis of relatedness among hyenas from
      multiple clans. Within a clan, patterns of relatedness reflected known pedigree
      relationships, and relatedness was higher within than among matrilines, even
      across generations. Although mean within-matriline relatedness varied among
      matrilines, it did not decline with matriline rank. On average, clan members were
      not related closely, due to high levels of male-mediated gene flow among clans,
      and relatedness declined very slightly across clan borders. Low mean relatedness
      within clans suggests that spotted hyenas cooperate with unrelated clan-mates
      against close paternal kin in other clans. Our data also suggest that spotted
      hyenas must derive large net direct fitness benefits from group living and
      cooperation.

PMID- 14717900
TI  - Fine-scale diversity and specificity in the most prevalent lineage of symbiotic
      dinoflagellates (Symbiodinium, Dinophyceae) of the Caribbean.
AB  - The success of coral reefs is due to obligate mutualistic symbioses involving
      invertebrates and photosynthetic dinoflagellate symbionts belonging to the genus
      Symbiodinium. In the Caribbean, the vast majority of octocorals and other
      invertebrate hosts associate with Symbiodinium clade B, and more selectively,
      with a single lineage of this clade, Symbiodinium B1/B184. Although B1/B184
      represents the most prevalent Symbiodinium in the Caribbean, there is little
      evidence supporting fine-scale diversity and host-alga specificity within this
      lineage. We explored simultaneously the questions of diversity and specificity in
      Symbiodinium B1/B184 by sequencing the flanking regions of two polymorphic
      microsatellites from a series of Symbiodinium clade B cultures along with
      Symbiodinium B1/B184 populations of the octocorals Pseudopterogorgia elisabethae,
      P. bipinnata and Gorgonia ventalina. Seven unique sequence variants were
      identified based on concatenation of the two loci. Phylogenetic analyses of these
      variants, which we refer to as phylotypes, recognized five as belonging to
      B1/B184, thus providing the first evidence of distinct taxa within this
      Symbiodinium lineage. Furthermore, sympatric P. elisabethae and P. bipinnata at
      San Salvador in the Bahamas were found to harbour distinct Symbiodinium B1/B184
      phylotypes, demonstrating unequivocally the existence of fine-scale specificity
      between Caribbean octocorals and these algae. Taken together, this study
      exemplifies the complex nature of Symbiodinium biodiversity and specificity.

PMID- 14717901
TI  - Founder effects and stochastic dispersal at the continental scale of the fungal
      pathogen of bananas Mycosphaerella fijiensis.
AB  - The worldwide destructive epidemic of the fungus Mycosphaerella fijiensis on
      banana started recently, spreading from South-East Asia. The founder effects
      detected in the global population structure of M. fijiensis reflected rare
      migration events among continents through movements of infected plant material.
      The main objective of this work was to infer gene flow and dispersal processes of
      M. fijiensis at the continental scale from population structure analysis in
      recently invaded regions. Samples of isolates were collected from banana
      plantations in 13 countries in Latin America and the Caribbean and in Africa. The
      isolates were analysed using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) and microsatellite molecular markers. The results
      indicate that a high level of genetic diversity was maintained at the plantation
      and the plant scales. The loci were at gametic equilibrium in most of the samples
      analysed, supporting the hypothesis of the existence of random-mating populations
      of M. fijiensis, even at the plant scale. A low level of gene diversity was
      observed in some populations from the Africa and Latin America-Caribbean regions.
      Nearly half the populations analysed showed a significant deviation from mutation
      drift equilibrium with gene diversity excess. Finally, a high level of genetic
      differentiation was detected between populations from Africa (FST = 0.19) and
      from the Latin America-Caribbean region (FST = 0.30). These results show that
      founder effects accompanied the recent invasion of M. fijiensis in both regions,
      suggesting stochastic spread of the disease at the continental scale. This spread
      might be caused by either the limited dispersal of ascospores or by movements of
      infected plant material.

PMID- 14717902
TI  - Effective size of two feral domestic cat populations (Felis catus L): effect of
      the mating system.
AB  - A variety of behavioural traits have substantial effects on the gene dynamics and
      genetic structure of local populations. The mating system is a plastic trait that
      varies with environmental conditions in the domestic cat (Felis catus) allowing
      an intraspecific comparison of the impact of this feature on genetic
      characteristics of the population. To assess the potential effect of the
      heterogenity of males' contribution to the next generation on variance effective
      size, we applied the ecological approach of Nunney & Elam (1994) based upon a
      demographic and behavioural study, and the genetic 'temporal methods' of Waples
      (1989) and Berthier et al. (2002) using microsatellite markers. The two cat
      populations studied were nearly closed, similar in size and survival parameters,
      but differed in their mating system. Immigration appeared extremely restricted in
      both cases due to environmental and social constraints. As expected, the ratio of
      effective size to census number (Ne/N) was higher in the promiscuous cat
      population (harmonic mean = 42%) than in the polygynous one (33%), when Ne was
      calculated from the ecological method. Only the genetic results based on Waples'
      estimator were consistent with the ecological results, but failed to evidence an
      effect of the mating system. Results based on the estimation of Berthier et al.
      (2002) were extremely variable, with Ne sometimes exceeding census size. Such low
      reliability in the genetic results should retain attention for conservation
      purposes.

PMID- 14717903
TI  - Postglacial colonization shows evidence for sympatric population splitting of
      Eurasian perch (Perca fluviatilis L) in Lake Constance.
AB  - Previous microsatellite analysis showed that two subpopulations of perch (Perca
      fluviatilis L) exist in Lake Constance. This raises questions of whether (i).
      Lake Constance was colonized by two populations that diverged in allopatry, or
      (ii). the two subpopulations diverged in sympatry. Sequence analysis of a 365 bp
      mtDNA fragment (5'-end of the D-loop) of perch from Lake Constance and adjacent
      waters revealed 10 haplotypes. We suggest colonization via the Danube river,
      based on the frequency and dispersion of haplotypes, and knowledge of the lake's
      palaeohydrological development. Pairwise FST-values using mitochondrial DNA
      sequences showed no significant population subdivision. Our study provides strong
      evidence that subpopulations of perch in Lake Constance have diverged in
      sympatry.

PMID- 14717904
TI  - Genetic structure among closely spaced leks in a peripheral population of lesser
      prairie-chickens.
AB  - We evaluated the genetic structure of birds from four closely spaced leks in a
      peripheral population of lesser prairie-chickens (Tympanuchus pallidicinctus).
      Analyses of molecular variance revealed significant genetic structuring among
      birds from different leks for six microsatellite loci (FST = 0.036; P = 0.002),
      but we found no genetic differentiation at the mtDNA control region. Significant
      deviations from Hardy-Weinberg revealed an excess of homozygote genotypes within
      each of the leks studied (FIS = 0.190-0.307), indicative of increased inbreeding.
      Estimates of relatedness using microsatellite data suggest that the genetic
      structuring among lesser prairie-chicken leks occurs in part because of a lek
      mating system in which males at some leks are related. Structuring may also be
      caused by stochastic effects associated with a historical decline in population
      size leading to small, semi-isolated leks and high site fidelity by reproductive
      males. Results from this study suggest that microspatial genetic structuring may
      occur in lek-mating bird species with low levels of dispersal.

PMID- 14717905
TI  - Horizontal transmission of Wolbachia by strepsipteran endoparasites? A response
      to Noda et al., 2001.

PMID- 14717906
TI  - Sodium glomerulopathy: tubuloglomerular feedback and renal injury in African
      Americans.
AB  - African Americans are prone to develop not only essential hypertension but also
      progressive renal injury. We present a simple model to explain salt-induced renal
      injury (sodium glomerulopathy) in African Americans, the central features of
      which are the tubuloglomerular feedback and the balance/imbalance between the
      vascular tones of the afferent and efferent glomerular arterioles. We propose
      that in African Americans, habitual consumption of high salt causes chronic
      intermittent tubular hyperperfusion of the macula densa, resulting in a rightward
      and upward resetting of the operating point for the tubuloglomerular feedback.
      The resetting of the operating point causes an imbalance between the vascular
      tones of the afferent/efferent arterioles, a rise in the glomerular capillary
      hydraulic pressure, and consequent hyperfiltration. Increased susceptibility to
      glomerular hyperfiltration of African Americans on a high salt intake may explain
      their proclivity to progressive renal injury associated with essential
      hypertension.

PMID- 14717907
TI  - Ear and kidney syndromes: molecular versus clinical approach.
AB  - The association between ear and kidney anomalies is not usually due to an insult
      to the embryo. In recent years, many essential development control genes that
      coordinate the assembly and function of kidney and ear have been discovered
      through the generation of animal mutants and have increased our understanding of
      the mechanisms of human oto-renal diseases. Here, we describe ear and kidney
      clinical syndromes and their molecular expression.

PMID- 14717908
TI  - The metabolic syndrome and uric acid nephrolithiasis: novel features of renal
      manifestation of insulin resistance.
AB  - BACKGROUND: Uric acid nephrolithiasis primarily results from low urinary pH,
      which increases the concentration of the insoluble undissociated uric acid,
      causing formation of both uric acid and mixed uric acid/calcium oxalate stones.
      These patients have recently been described as exhibiting features of insulin
      resistance. This study was designed to evaluate if insulin resistance is
      associated with excessively low urinary pH in overtly healthy volunteers (non
      stone formers) and if insulin resistance may explain the excessively low urinary
      pH in patients with uric acid nephrolithiasis. METHODS: Fifty-five healthy
      volunteers (non stone-formers) with a large range of body mass index and 13
      patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic
      euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of
      adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection
      before and during the hyperinsulinemic phase of the clamp studies. RESULTS: For
      the non-stone former population, low insulin sensitivity measured as glucose
      disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P=
      0.01). In addition to the previously described acidic urine pH and
      hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to
      be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs.
      normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008).
      Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at
      baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia
      excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002)
      and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2
      hr P < 0.0001). CONCLUSION: We conclude that one renal manifestation of insulin
      resistance may be low urinary ammonium and pH. This defect can result in
      increased risk of uric acid precipitation despite normouricosuria.

PMID- 14717909
TI  - Sulfite-mediated oxidative stress in kidney cells.
AB  - BACKGROUND: Chronic renal failure has been associated with oxidative stress.
      Serum sulfite, sulfate, cysteine, homocysteine, cysteine sulfinic acid, and gamma
      glutamylcysteine are elevated in patients on hemodialysis, suggesting an
      accelerated catabolism of sulfur-containing amino acids or a reduced elimination
      of sulfite/sulfate, or both. Administration of metabisulfite has also been shown
      to damage kidney cells. METHODS: Measurement of reactive oxygen species (ROS) was
      performed with the fluorescence of dichlorofluorescein (DCF), and that of
      intracellular ATP was by the luciferin-luciferase reaction. Oxidation of sulfite
      and succinate by isolated mitochondria from rat kidney was monitored
      polarographically. The fluorescent probe, 5, 5', 6, 6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine iodide (JC-1) was employed to assess any loss
      in membrane potential in energized respiring mitochondria. Activities of
      glutamate and malate dehydrogenases (GDH, MDH, respectively) were assayed by the
      spectrophotometric measurement of NADH. Sulfite was determined by HPLC
      fluorimetric measurement of monochlorobimane-sulfite and cell viability was by
      the MTT procedure. RESULTS: An immediate increase in ROS followed exposure of
      Madin-Darby canine kidney (MDCK), type II, and opossum kidney (OK) cells to 5-500
      micromol/L sulfite. Depletion of intracellular ATP was also observed. A low rate
      of oxidation of 100 micromol/L sulfite was observed polarographically in isolated
      kidney mitochondria, but ADP-stimulated State 3 respiration was not apparent. ATP
      biosynthesis from the oxidation of glutamate in rat kidney mitochondria was
      significantly inhibited by coincubation with 100 micromol/L sulfite; this was not
      the case with malate, succinate, and TMPD/ascorbate. However, activities of both
      GDH and MDH in kidney mitochondrial extract were inhibited. The mitochondrial
      membrane potential and cell viability were not compromised. CONCLUSION:
      Micromolar sulfite elicited an immediate increase in ROS in MDCK, type II, and OK
      cells. This was accompanied by a depletion of intracellular ATP, which could be
      explained by its inhibitory effect on mitochondrial GDH. Although MDH was
      similarly inhibited, the impact was buffered by the high level of this enzyme in
      kidney mitochondria.

PMID- 14717910
TI  - Glucocorticoid receptors, in vitro steroid sensitivity, and cytokine secretion in
      idiopathic nephrotic syndrome.
AB  - BACKGROUND: Glucocorticoids (GC) represent the mainstay of treatment of
      idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of
      the disease. We evaluated basal secretion of cortisol, number and affinity of
      glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin
      A (Con-A)-stimulated peripheral blood mononuclear cell (PBMC) proliferation, and
      cytokine secretion in patients with INS. METHODS: Blood and saliva were obtained
      from 20 INS patients in relapse and 11 control patients. Cortisol concentrations
      were measured by radioimmunoassay. PBMC were isolated for binding and in vitro GC
      sensitivity assays. Cytokines were measured in supernatants of PBMC culture by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Salivary cortisol
      concentrations were similar in INS patients and control patients. Density and
      affinity of GC receptors were similar in steroid-sensitive (SS) patients and
      control, whereas in steroid-resistant (SR) patients they were variable.
      Lymphocyte proliferation after Con-A stimulation was inhibited by Dex in a dose
      dependent manner in control and SS patients. Control and all clinically SS
      patients were steroid-sensitive by in vitro test, but control patients
      significantly presented more suppression of PBMC proliferation compared with SS
      patients. Basal- and Con-A-stimulated interleukin (IL)-6, IL-10, interferon (IFN)
      gamma, and tumor necrosis factor (TNF)-alpha levels were similar in control and
      INS patients, and all cytokines but IL-10 were significantly inhibited by Dex 10
      6 mol/L. In SR patients, cytokine secretion remained elevated after treatment
      with high doses of Dex. CONCLUSION: Abnormalities of number and affinity of the
      GC receptor and altered secretion of cytokines may be involved in tissue
      sensitivity to GC in INS patients.

PMID- 14717911
TI  - Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats
      with established renal injury.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) has been reported to prevent injury in
      several models of renal disease; however, whether HGF can also retard progression
      of established renal disease is not known. METHODS: The aim of the present study
      was to examine the effects of HGF on progression of chronic renal disease in rats
      with remnant kidneys and established injury. Studies were performed in rats that
      underwent subtotal nephrectomy, were observed for two weeks without therapy, and
      then randomized to receive HGF or vehicle by continuous infusion for an
      additional two weeks. RESULTS: HGF administration was associated with a reduction
      in morphologic evidence of interstitial, but not glomerular injury. The
      beneficial effects of HGF were not associated with reductions in the expression
      of transforming growth factor-beta (TGF-beta), or in the extent epithelial cell
      apoptosis or transdifferentiation. Rather, HGF appeared to induce fibrinolytic
      pathways by increasing expression of metalloproteinase-9 (MMP-9) and decreasing
      levels of plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of
      metalloproteinase-1 (TIMP-2). HGF administration was also associated with an
      apparent increase in renal endothelin production and a significant reduction in
      glomerular capillary pressure. CONCLUSION: These findings suggest that HGF can
      retard progression of chronic renal disease even after injury is already
      established, primarily by promoting matrix degradation.

PMID- 14717912
TI  - Gene expression profiles of circulating leukocytes correlate with renal disease
      activity in IgA nephropathy.
AB  - BACKGROUND: The goal of these studies was to explore the possibility of using
      gene expression profiles of circulating leukocytes as a functional fingerprint of
      nephritic disease activity. METHODS: This feasibility study utilized IgA
      nephropathy (IgAN) as a model system. Genes differentially expressed in IgAN
      patients were identified by Affymetrix GeneChip microarrays, and compared with
      gene expression of focal segmental glomerulosclerosis (FSGS), minimal change
      disease, antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, and with
      healthy volunteers. Of the genes identified, 15 transcriptionally up-regulated
      were validated in a larger cohort of patients using TaqMan polymerase chain
      reaction (PCR). To test whether increased expression of these genes correlated
      with disease activity, cluster analyses were performed utilizing the TaqMan PCR
      values. Taking a mathematical approach, we tested whether gene expression values
      were correlative with kidney function, as reflected by serum creatinine and
      creatinine clearance values. RESULTS: We identified 15 genes significantly
      correlative with disease activity in IgAN. This gene signature of IgAN patients'
      leukocytes reflected kidney function. This was demonstrated in that
      mathematically generated theoretical values of serum creatinine and creatinine
      clearance correlated significantly with actual IgAN patient values of serum
      creatinine and creatinine clearance. There was no apparent correlation with
      hematuria and proteinuria. The expression levels of this same gene set in ANCA
      glomerulonephritis or Lupus nephritis patients were not correlative with serum
      creatinine or creatinine clearance values. CONCLUSION: These data indicate that
      leukocytes carry informative disease-specific markers of pathogenic changes in
      renal tissue.

PMID- 14717913
TI  - Chronic COX-2 inhibition reduces medullary HSP70 expression and induces papillary
      apoptosis in dehydrated rats.
AB  - BACKGROUND: Papillary cells adapt to their hyperosmotic environment by
      accumulating organic osmolytes and by enhanced synthesis of heat shock protein 70
      (HSP70), which protect against high-solute concentrations. Because cyclooxygenase
      2 (COX-2) is expressed abundantly in the renal papilla and is induced by
      dehydration, and because HSP70 expression is stimulated by specific
      prostaglandins, COX-2 inhibition may interfere with cellular osmoadaptation.
      METHODS: In vivo, rats received rofecoxib before water deprivation. Medullary
      expression of several tonicity-responsive genes was analyzed and apoptosis was
      monitored by transferase-mediated dUTP nick-end labeled (TUNEL) staining and
      determination of papillary caspase-3 activity. In vitro, inner medullary
      collecting duct 3 (IMCD3) cells were exposed to hypertonic medium containing a
      COX-2-specific inhibitor. Thereafter, expression of tonicity-responsive genes was
      analyzed and resistance to high-solute concentrations was examined. Further, the
      effect of Delta 12-PGJ2, a urinary prostaglandin, and of HSP70 overexpression on
      resistance against high urea concentration, was evaluated. RESULTS: Rofecoxib
      treatment significantly increased urine osmolality due to higher urea
      concentrations, but reduced papillary HSP70 abundance by 50%. TUNEL staining
      showed numerous apoptotic cells in the papilla, associated with increased caspase
      3 activity. These in vivo results were confirmed by experiments on cultured IMCD3
      cells, in which COX-2 inhibition impaired the tonicity-induced up-regulation of
      HSP70 expression and rendered the cells susceptible to high urea concentrations.
      Furthermore, Delta 12-PGJ2 increased both HSP70 expression and resistance against
      high urea, which was causally linked to higher HSP70 levels. CONCLUSION: These
      observations support the view that chronic COX-2 inhibition reduces medullary
      HSP70 expression, thus rendering papillary cells susceptible to damage by high
      urea concentrations, especially when accompanied by dehydration.

PMID- 14717914
TI  - The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation
      and wound repair.
AB  - BACKGROUND: Cardiovascular diseases are the major causes of mortality in uremic
      patients, and the vascular endothelium is dysfunctional in uremia. We
      hypothesized that uremic retention solutes may be among the factors involved in
      this endothelial dysfunction. We therefore investigated the in vitro effect of a
      large panel of uremic retention solutes (guanidino compounds, polyamines,
      oxalate, myoinositol, urea, uric acid, creatinine, indoxyl sulfate, indole-3
      acetic acid, p-cresol, hippuric acid, and homocysteine) on endothelial
      proliferation. In addition, we tested the effect of uremic solutes that altered
      proliferation on endothelial wound repair. METHODS: Human umbilical vein
      endothelial cells (HUVEC) were incubated with uremic retention solutes at
      concentrations in the range found in uremic patients. Protein-bound uremic
      solutes were also tested in the presence of 4% human albumin. Then, we determined
      the effect of each uremic solute on endothelial proliferation by a 5-bromo-2
      deoxy-uridine (BrdU) labeling assay. In addition, confluent endothelial
      monolayers were injured, incubated with uremic solutes that altered endothelial
      proliferation, and the surface of the wound was measured at different intervals
      by image analysis. RESULTS: Endothelial proliferation was inhibited by two
      protein-bound uremic retention solutes: p-cresol and indoxyl-sulfate. Inhibition
      of endothelial proliferation by p-cresol was dose-dependent. Moreover, p-cresol
      and indoxyl sulfate decreased endothelial wound repair. The presence of albumin
      did not affect the inhibitory effect of these solutes on endothelial
      proliferation, but the decrease in endothelial wound repair was less marked in
      the presence of albumin. CONCLUSION: We demonstrated that both p-cresol and
      indoxyl sulfate decrease endothelial proliferation and wound repair. These
      solutes could play a role in endothelial dysfunction observed in uremic patients.

PMID- 14717915
TI  - Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial
      cells.
AB  - BACKGROUND: Erythropoietin has recently been found to have cytoprotective effects
      in the central nervous system (CNS) and retina. The purpose of this study was to
      determine if darbepoetin alfa (DA) has cytoprotective properties in renal
      tissues. METHODS: DA was studied in LLC/PK1 and mesangial cells. Renal cellular
      injury was induced in different experiments by prostaglandin D2 synthase (PGDS),
      camptothecin, hydrogen peroxide, and hypoxia. Cellular proliferation and
      apoptosis were measured [apoptosis by terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay or by
      caspase-3 activity]. In a separate experiment, an inactive form of erythropoietin
      alfa was used to study receptor effects. RESULTS: DA protected against the
      antiproliferative effects of PGDS. In both LLC/PK1 (TUNEL and caspase-3) and
      mesangial cells (TUNEL), DA reduced the apoptotic stimulus of PGDS. Epoetin alfa
      was also found to reduce apoptosis. In LLC/PK1 cells, DA reduced apoptosis
      induced by camptothecin, but not hydrogen peroxide. DA reduced LLC/PK1 apoptosis
      induced by hypoxia when added 24 hours before hypoxia, but not when given
      concurrent with the hypoxic stimulus. Erythropoietin inactive did not protect
      against PGDS-induced apoptosis. CONCLUSION: DA has renal antiapoptotic effects
      for both toxic and hypoxic stimuli. The effect may be mediated via the
      Erythropoietin receptor.

PMID- 14717916
TI  - Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in
      the rat in vivo.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta), a profibrotic cytokine
      involved in many scarring processes, has to be activated extracellularly before
      it can bind to its receptors. Thrombospondin 1 (TSP1), a multifunctional
      matricellular glycoprotein, has been identified as an activator of TGF-beta in in
      vitro systems and during mouse postnatal development in vivo. TSP1 is expressed
      de novo in many inflammatory disease processes, including glomerular disease.
      METHODS: In this study we investigated whether peptides specifically interfering
      with the activation process of TGF-beta by TSP1 may be able to block activation
      of TGF-beta in an in vivo model of mesangial proliferative glomerulonephritis.
      RESULTS: Continuous intravenous infusion of blocking peptide by minipumps
      significantly reduced expression of active TGF-beta in glomeruli on day 7 of
      disease as indicated by immunohistochemistry, bioassay, and activation of the TGF
      beta signal transduction pathway, while total TGF-beta expression was unchanged.
      Inhibition of glomerular TGF-beta activation was accompanied by a decrease of
      glomerular extracellular matrix accumulation and proteinuria, but was without
      effect on mesangial cell proliferation or influx of monocytes/macrophages.
      CONCLUSION: TSP1 is a major endogenous activator of TGF-beta in experimental
      inflammatory glomerular disease. Drugs interfering with the activation of TGF
      beta by locally produced TSP1 may be considered as a future specific treatment of
      scarring kidney disease.

PMID- 14717917
TI  - Transgene of MIF induces podocyte injury and progressive mesangial sclerosis in
      the mouse kidney.
AB  - BACKGROUND: Recent evidence suggests that macrophage migration inhibitory factor
      (MIF) is a proinflammatory cytokine that plays a pathogenic role in
      glomerulonephritis. Renal expression of MIF is up-regulated in infiltrating and
      intrinsic renal cells, which include glomerular epithelial cells. The aim of the
      current study was to further clarify the role of MIF produced by podocytes in the
      process of renal disease. METHODS: We generated transgenic mice carrying a murine
      MIF cDNA driven by cytomegalovirus enhancer and beta-actin/beta-globin promoter,
      a hybrid promoter transactivated in podocytes in vivo. RESULTS: MIF expression
      was markedly up-regulated in podocytes in neonatal and adult transgenic kidneys.
      A longitudinal study of the MIF transgenic mice demonstrated a progressive matrix
      increase in mesangium accompanied by collagen IV accumulation, representing no
      significant glomerular cell hypercellularity. The glomeruli in transgenic kidney
      were not accompanied by influx of macrophages and T cells at the early stage of
      disease progression. Although a significant number of the mice showing higher
      expression of MIF died from renal failure at 8 weeks, most of them survived with
      significant proteinuria and progressive renal failure. Podocytes of transgenic
      mice frequently underwent characteristic ultrastructural changes, such as cell
      flattening, contracted foot processes, and villous transformation. In addition,
      immunohistochemical expression of synaptopodin, an actin-associated protein
      distributed in differentiated podocyte foot process, was significantly attenuated
      in transgenic kidney. CONCLUSION: Our results indicate that podocyte-expressed
      MIF could induce an injury of podocytes themselves, thereby accelerating the
      progression of glomerulosclerosis and leading to end-stage renal failure.

PMID- 14717918
TI  - Polycystic kidney syndrome in New Zealand White rabbits resembling human
      polycystic kidney disease.
AB  - BACKGROUND: Cystic kidney diseases are an important cause of morbidity and
      mortality in humans. Small animal models are needed to more fully explore the
      complex expression patterns and pathobiology of this group of heritable diseases.
      METHODS: We performed a 15-year retrospective analysis of cases in our laboratory
      animal diagnostic archives to determine the prevalence of cystic kidney disease
      in New Zealand White rabbits. RESULTS: Out of 203 records with documented renal
      histopathology, we identified and defined 7 cases of polycystic kidney syndrome
      (PKS) by 3 morphologic criteria: (1) cysts or microcysts derived from tubules,
      glomeruli, or both; (2) loose mesenchymal expansion of cortical and/or medullary
      interstitium; and (3) irregular thickening, thinning, and splitting of basement
      membranes. PKS was associated with hypercalcemia and hypercreatinemia (P < 0.01),
      and arterial mineralization resembling Monckeberg's medial calcific sclerosis. In
      the liver, mild chronic cholangitis with cholangiodysplasia and fibrosis was
      common. Anorexia and lethargy were the clinical signs most often reported.
      CONCLUSION: Clinicopathologic characterization of PKS in New Zealand White
      rabbits revealed similarities to both autosomal-dominant and autosomal-recessive
      polycystic kidney diseases of humans. Awareness of polycystic kidney syndrome in
      New Zealand White rabbits will allow investigators to avoid using affected
      animals in unrelated renal research. Prospective studies are needed to define the
      underlying cause(s) of polycystic kidney syndrome in New Zealand White rabbits,
      which may be an important new small animal model of human cystic kidney diseases.

PMID- 14717919
TI  - Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis
      factor-alpha.
AB  - BACKGROUND: Salicylate was recently shown to provide protection against cisplatin
      nephrotoxicity in rats. We have demonstrated that enhanced tumor necrosis factor
      alpha (TNF-alpha) production mediates, in part, cisplatin nephrotoxicity. The
      purpose of this study was to determine if the protective effects of salicylate
      were mediated through inhibition of TNF-alpha in vivo and to explore the
      mechanism of inhibition in vitro. METHODS: The effects of treatment with
      cisplatin alone and in combination with sodium salicylate in mice on renal
      function, histology, and gene expression were determined. The effects of
      cisplatin and salicylate on TNF-alpha expression, nuclear factor kappa B (NF
      kappa B) activity, and apoptosis were determined in vitro using cultured murine
      proximal tubule cells. RESULTS: Salicylate significantly reduced both the
      functional and histologic evidence of cisplatin renal injury. Cisplatin increased
      the renal expression of TNF-alpha, monocyte chemoattractant protein-1 (MCP-1),
      intercellular adhesion molecule (ICAM)-1, heme oxygenase-1, TNF receptor 1
      (TNFR1), and TNF receptor 2 (TNFR2). Treatment with sodium salicylate blunted the
      increase in TNF-alpha mRNA and also reduced serum TNF-alpha protein levels.
      Salicylate had little protective effect when administered with cisplatin to TNF
      alpha-deficient mice. Cisplatin increased the degradation of I kappa B (I kappa
      B) in a time-dependent manner and also increased nuclear NF-kappa B binding
      activity. Salicylate inhibited I kappa B degradation and NF-kappa B binding
      activity in the presence of cisplatin. In addition, salicylate inhibited the
      cisplatin induced TNF-alpha mRNA increase in mouse proximal tubule epithelial
      (TKPT) cells. CONCLUSION: These results indicate that salicylate acts via
      inhibition of TNF-alpha production to reduce cisplatin nephrotoxicity. The
      inhibition of TNF-alpha production may be mediated via stabilization of I kappa
      B.

PMID- 14717920
TI  - 5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental
      ischemia/reperfusion.
AB  - BACKGROUND: Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by
      strand breaks in DNA, plays an important role in the development of
      ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the
      effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5
      AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat
      kidney in vitro and in vivo. METHODS: Primary cultures of rat renal proximal
      tubular cells, subjected to oxidative stress caused by hydrogen peroxide (H2O2),
      were incubated with increasing concentrations of 5-AIQ (0.01 to 1 mmol/L) after
      which PARP activation, cellular injury, and cell death were measured. In in vivo
      experiments, anesthetized male Wistar rats were subjected to renal bilateral
      ischemia (45 minutes) followed by reperfusion (6 hours) in the absence or
      presence of 5-AIQ (0.3 mg/kg) after which renal dysfunction, injury and PARP
      activation were assessed. RESULTS: Incubation of proximal tubular cells with H2O2
      caused a substantial increase in PARP activity, cellular injury, and cell death,
      which were all significantly reduced in a concentration-dependent by 5-AIQ
      [inhibitory concentration 50 (IC50) approximately 0.03 mmol/L]. In vivo, renal
      I/R resulted in renal dysfunction, injury, and PARP activation, primarily in the
      proximal tubules of the kidney. Administration of 5-AIQ significantly reduced the
      biochemical and histologic signs of renal dysfunction and injury and markedly
      reduced PARP activation caused by I/R. CONCLUSION: This study demonstrates that 5
      AIQ is a potent, water soluble inhibitor of PARP activity, which can
      significantly reduce (1) cellular injury and death caused to primary cultures of
      rat proximal tubular cells by oxidative stress in vitro, and (2) renal injury and
      dysfunction caused by I/R of the kidney of the rat in vivo.

PMID- 14717921
TI  - Expression of p16INK4a and other cell cycle regulator and senescence associated
      genes in aging human kidney.
AB  - BACKGROUND: Somatic cells in vitro have a finite life expectancy before entering
      a state of senescence. If this state has an in vivo counterpart, it could
      contribute to organ aging. We have previously shown that human kidney cortex
      displays telomere shortening with age. In the present study, we evaluated the
      relationship between renal age in humans and a number of phenomena associated
      with cellular senescence in vitro. METHODS: Human kidney specimens were obtained
      at 8 weeks to 88 years of age and were assessed for changes related to aging.
      RESULTS: We found that human kidneys expressed relatively constant levels of
      mRNAs for genes potentially related to senescence. Among the candidate genes
      surveyed, the cell cycle regulator p16INK4a emerged with the strongest
      association with renal aging for both mRNA and protein expression. Proliferation
      as measured by Ki-67 expression was inversely correlated with p16INK4a
      expression, compatible with a role for p16INK4a as an irreversible cell cycle
      inhibitor. Cyclooxygenase 1 and 2 (COX-1 and COX-2) mRNA expression was elevated
      in older kidneys, associated with increased protein expression. Comparison of
      gene expression with age-related histologic changes revealed that
      glomerulosclerosis correlated with p16INK4a and p53, whereas interstitial
      fibrosis and tubular atrophy were associated with p16INK4a, p53, COX-1,
      transforming growth factor-beta 1 (TGF-beta 1), and heat shock protein A5
      (HSPA5). CONCLUSION: We conclude that some changes observed in cellular
      senescence in vitro do occur in human kidney with age, particularly in the renal
      cortex, in some cases correlating with histologic features. P16INK4a emerged with
      the most consistent correlations with age and histologic changes and inversely
      correlated with cell replication.

PMID- 14717922
TI  - The classification of glomerulonephritis in systemic lupus erythematosus
      revisited.
AB  - The currently used classification reflects our understanding of the pathogenesis
      of the various forms of lupus nephritis, but clinicopathologic studies have
      revealed the need for improved categorization and terminology. Based on the 1982
      classification published under the auspices of the World Health Organization
      (WHO) and subsequent clinicopathologic data, we propose that class I and II be
      used for purely mesangial involvement (I, mesangial immune deposits without
      mesangial hypercellularity; II, mesangial immune deposits with mesangial
      hypercellularity); class III for focal glomerulonephritis (involving <50% of
      total number of glomeruli) with subdivisions for active and sclerotic lesions;
      class IV for diffuse glomerulonephritis (involving > or =50% of total number of
      glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement,
      and also with subdivisions for active and sclerotic lesions; class V for
      membranous lupus nephritis; and class VI for advanced sclerosing lesions.
      Combinations of membranous and proliferative glomerulonephritis (i.e., class III
      and V or class IV and V) should be reported individually in the diagnostic line.
      The diagnosis should also include entries for any concomitant vascular or
      tubulointerstitial lesions. One of the main advantages of the current revised
      classification is that it provides a clear and unequivocal description of the
      various lesions and classes of lupus nephritis, allowing a better standardization
      and lending a basis for further clinicopathologic studies. We hope that this
      revision, which evolved under the auspices of the International Society of
      Nephrology and the Renal Pathology Society, will contribute to further
      advancement of the WHO classification.

PMID- 14717923
TI  - Regulation of gene expression by dietary Ca2+ in kidneys of 25-hydroxyvitamin D3
      1 alpha-hydroxylase knockout mice.
AB  - BACKGROUND: Pseudovitamin D deficiency rickets (PDDR) is an autosomal disease,
      characterized by undetectable levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3),
      rickets and secondary hyperparathyroidism. Mice in which the 25-hydroxyvitamin D3
      1 alpha-hydroxylase (1 alpha-OHase) gene was inactivated, presented the same
      clinical phenotype as patients with PDDR. METHODS: cDNA Microarray technology was
      used on kidneys of 1 alpha-OHase knockout mice to study the expression profile of
      renal genes in this Ca2+-related disorder. Genome wide molecular events that
      occur during the rescue of these mice by high dietary Ca2+ intake were studied by
      the use of 15K cDNA microarray chips. RESULTS: 1 alpha-OHase knockout mice fed a
      normal Ca2+ diet developed severe hypocalcemia, rickets and died with an average
      life span of 12 +/- 2 weeks. Intriguingly, 1 alpha-OHase-/- mice supplemented
      with an enriched Ca2+ diet were normocalcemic and not significantly different
      from wild-type mice. Inactivation of the 1 alpha-OHase gene resulted in a
      significant regulation of +/- 1000 genes, whereas dietary Ca2+ supplementation of
      the 1 alpha-OHase-/- mice revealed +/- 2000 controlled genes. Interestingly, 557
      transcripts were regulated in both situations implicating the involvement in the
      dietary Ca2+-mediated rescue mechanism of the 1 alpha-OHase-/- mice. Conspicuous
      regulated genes encoded for signaling molecules like the PDZ-domain containing
      protein channel interacting protein, FK binding protein type 4, kinases, and
      importantly Ca2+ transporting proteins including the Na+-Ca2+ exchanger,
      calbindin-D28K and the Ca2+ sensor calmodulin. CONCLUSION: Dietary Ca2+ intake
      normalized disturbances in the Ca2+ homeostasis due to vitamin D deficiency that
      were accompanied by the regulation of a subset of renal genes, including well
      known renal Ca2+ transport protein genes, but also genes not previously
      identified as playing a role in renal Ca2+ handling.

PMID- 14717924
TI  - The role of adrenomedullin and receptors in glomerular hyperfiltration in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Since adrenomedullin (AM) elicits vasodilatation by binding to
      specific AM receptors consisted of calcitonin-receptor-like receptor
      (CRLR)/receptor-activity-modifying protein 2 (RAMP2) or CRLR/receptor-activity
      modifying protein 3 (RAMP3) on endothelial cells and stimulating nitric oxide
      production, AM possibly involves in glomerular capillary dilatation in early
      phase of diabetic nephropathy. METHODS: Streptozotocin (STZ)-induced diabetic
      Sprague-Dawley rats at 4 weeks after the injection were employed for expression
      studies of AM, RAPM2, and RAMP3. The measurement of AM peptide levels in kidney
      tissue, plasma, and urine was performed. Human aortic endothelial cells (HAEC)
      were used to investigate functional link between glucose-induced AM production
      and nitric oxide release. RESULTS: STZ rats showed glomerular hypertrophy and
      increased urinary NO2- and NO3- excretion. By Northern blot analyses, AM and
      RAPM2 mRNAs significantly increased in the kidneys of STZ rats, while RAMP3 mRNA
      was not altered. In STZ rats, AM peptide was actively secreted into urine (1280
      +/- 360 fmol/day vs. control 110 +/- 36 fmol/day). AM peptide was mainly detected
      on cortical and medullary collecting duct cells in control rat kidneys and AM
      peptide and mRNA were up-regulated on afferent arterioles and glomeruli of STZ
      rats. RAMP2 expression was detected on afferent arterioles and not in glomeruli
      in control rats and it was up-regulated on glomerular endothelial cells in STZ
      rats. In HAEC culture, d-glucose stimulated AM and nitric oxide production and
      they were suppressed by addition of AM antisense oligodeoxynucleotides.
      CONCLUSION: Up-regulated expression of AM and RAMP2 in afferent arterioles and
      glomeruli may be related to selective dilatation of glomerular capillary in acute
      phase of type 1 diabetes.

PMID- 14717925
TI  - Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule
      cells.
AB  - BACKGROUND: Recent evidence from this laboratory have demonstrated a critical
      role of phospholipase A2 (PLA2) and arachidonic acid in angiotensin II type 2
      (AT2) receptor-mediated kinase activation in renal epithelium independent of
      phosphoinositide- specific phospholipase C (PLC) and without the necessity of
      eicosanoid biosynthesis. In the present study, we investigated whether cyclic
      stress phosphorylates and activates the mitogen-activated protein kinase (MAPK)
      pathway and whether PLA2 activation mediates mechanotransduction in renal
      epithelial cells. The rational for studying kidney epithelial cells relates to
      their similarity to podocytes, which undergo mechanical stretch related to
      changes in intraglomerular pressure. METHODS: To produce strain or stretch,
      primary cultures of rabbit proximal tubular cell cells are grown in tissue
      culture wells having a collagen-coated Silastic deformable membrane bottoms and
      applying vacuum to the well to generate alternating cycles of stretch and
      relaxation (30 cycles/min). RESULTS: We found that cyclic stretching of rabbit
      proximal tubular cells caused a time- and intensity-dependent activation of
      extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in proximal tubular
      cells as detected by its phosphorylation. In addition, mechanical stretch induced
      PLA2 activation and a subsequent rapid release of arachidonic acid. Inhibition of
      PLA2 by mepacrine and methyl arachidonyl fluorophosphonate ketone (AACOCF3)
      attenuated both arachidonic acid release and ERK 1/2 activation by cyclic
      stretch, supporting the importance of PLA2 as a mediator of mechanotransduction
      in renal proximal tubular cells. A requirement for extracellular Ca2+ and stretch
      activated Ca2+ channels was also documented. Complete inhibition of ERK 1/2 by
      PD98059, a MAPK kinase (MEK) inhibitor, did not suppress stretch- induced PLA2
      activation and arachidonic acid release, suggesting the later events were
      upstream of ERK 1/2. Cyclic stretch also caused rapid phosphorylation of the EGF
      receptor kinase and c-Src. Furthermore, arachidonic acid itself induced time- and
      dose-dependent phosphorylation of c-Src. In addition, the c-Src inhibitor PP2 and
      selective EGF receptor kinase inhibitor AG1478 attenuated both ERK 1/2 and EGF
      receptor phosphorylation by cyclic stretch. CONCLUSION: PLA2 dependence for ERK
      1/2 activation in response to cyclic stretch in proximal tubular epithelial cells
      was established in this report. In addition, these findings indicate cyclic
      stretch increased the tyrosine phosphorylation of the EGF receptor and c-Src and
      that c-Src acts upstream of the EGF receptor to mediate its phosphorylation,
      whereby both are critical for stretch- induced ERK 1/2 activation in rabbit
      proximal tubular cells. These observations documents for the first time a
      mechanism of mechanical stretch-induced kinase activation mediated by stretch
      activated Ca2+ channels and PLA2-dependent release of arachidonic acid.

PMID- 14717926
TI  - Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt
      protoporphyrin.
AB  - BACKGROUND: Heme oxygenase (HO) products have a protective role in acute renal
      failure (ARF) that may be hemodynamically mediated because the HO-derived carbon
      monoxide (CO) is an important control system of arteriolar tone. The vascular
      effects of HO may be caused directly through changes in CO synthesis, and
      indirectly by alterations in nitric oxide (NO) release. The present study
      evaluated in vivo the renal effects of a heme oxygenase inhibitor,
      Co(III)Protoporphyrin (CoPP) alone or in combination with the CO donor
      dimanganese decacarbonyl (Mn2(CO)10). METHODS: All drugs were administered into
      the renal artery of anesthetized rats. Changes in renal cortical nitric oxide
      concentration were measured in vivo electrochemically. RESULTS: The intrarenal
      administration of the CO donor Mn2(CO)10 increased blood carboxyhemoglobin levels
      (+74%), renal blood flow (+54%), glomerular filtration (+38%), and urinary cGMP
      excretion (+128%). On the other hand, the inhibition of renal HO with CoPP
      progressively induced an ARF characterized by a drop in renal blood flow (-77%),
      glomerular filtration (-93%), and urinary cGMP excretion (-93%). These
      deleterious effects of HO inhibition on renal function were nearly abolished by
      supplementing CO with the coadministration of Mn2(CO)10+ CoPP, indicating that
      they may be caused by inhibition of CO synthesis and the resulting hemodynamic
      changes. In addition, CoPP lowered the renal cortical NO concentration (-21%) and
      also decreased the urinary excretion of nitrates/nitrites, while Mn2(CO)10
      increased renal NO levels (+20%) and raised the excretion of nitrates/nitrites,
      suggesting that changes in NO release may contribute to the renal effects of the
      HO-CO system. CONCLUSION: These results indicate that heme oxygenase-derived CO
      plays a cardinal role in the control of renal hemodynamics and glomerular
      filtration.

PMID- 14717927
TI  - Temporary losartan or captopril in young SHR induces malignant hypertension
      despite initial normotension.
AB  - BACKGROUND: Exposure of normotensive rats to angiotensin-converting enzyme (ACE)
      inhibitors in early life causes hypertrophy of intrarenal arteries. Similar
      defects have been found in knockout mice lacking angiotensinogen, ACE, or
      angiotensin II type 1 (AT1) receptors. On the other hand, transient inhibition of
      the renin-angiotensin system from 2 weeks of age in spontaneously hypertensive
      rats (SHR), either with ACE inhibitors or with AT1 receptor antagonists partially
      prevents the increase in blood pressure. However, permanent treatment of SHR from
      conception onwards with ACE inhibitors completely prevents hypertension. Although
      these studies demonstrated protection from hypertension-induced changes in the
      heart and large arteries, renal arteries were not studied and follow-up did not
      extend beyond 6 months of age. We postulated that while brief exposure to ACE
      inhibitors or AT1 receptor antagonists in young SHR would temporarily decrease
      blood pressure, it would also be associated with development of intrarenal
      arterial malformation, and ultimately have deleterious effects. METHODS: Direct
      effects on intrarenal arterial morphology of an ACE inhibitor (captopril, 100
      mg/kg/day) and an AT1 receptor antagonist (losartan, 50 mg/kg/day), administered
      from the last week of gestation until 8 weeks of age were examined in SHR. After
      stopping treatment at 8 weeks, we continued to monitor blood pressure until
      spontaneous death. RESULTS: Systolic blood pressure at 8 weeks was normalized by
      captopril and losartan (SHR control 187 +/- 8 mm Hg; captopril 118 +/- 5 mm Hg;
      and losartan 120 +/- 9 mm Hg). However, by 30 weeks, blood pressure had increased
      to control SHR levels. At 4 weeks, the media of renal arteries and arterioles was
      hypertrophied. Marked smooth muscle cell hyperplasia of cortical arteries
      resulted in significantly increased wall thickness by 8 weeks, despite similar
      external diameter. Arterial wall structure was disrupted, with fragmentation of
      elastic fibers and irregular distribution of collagen type I fibers. After
      stopping treatment, the rats gradually began to show poor health and all had died
      by 1 year of age, while all 1-year-old control SHR females were in good health.
      The cause of morbidity and mortality in the rats treated in early life was
      clearly malignant hypertension. Severe hypertrophy of renal arterioles was found,
      as well as cerebral hemorrhage. CONCLUSION: Despite initial normalization of
      blood pressure interference with the renin-angiotensin system during a crucial
      stage of development in SHR can initiate marked smooth muscle cell hyperplasia
      and disruption of the wall structure of the intrarenal arteries. Subsequent
      progression of this intrarenal process after cessation of treatment suggests an
      independent process that eventually results in malignant hypertension and early
      death.

PMID- 14717928
TI  - Is there an association between level of adult blood pressure and nephron number
      or renal filtration surface area?
AB  - BACKGROUND: Reductions in renal filtration surface area (FSA) have been linked to
      development of hypertension. This study investigated whether there are direct
      relationships, in the adult rat, between levels of blood pressure and nephron
      number or total renal FSA. METHODS: F1 and F2 offspring were generated from a
      spontaneously hypertensive rat (SHR)/Wistar Kyoto (WKY) rat cross. Tail-cuff
      systolic blood pressure was measured twice weekly from 5 to 15 weeks of age and
      mean arterial blood pressure determined prior to sacrifice. At 15 weeks of age,
      the rats were perfusion-fixed and glomerular (and thereby nephron) number,
      glomerular size, total length, and surface area of glomerular capillaries and
      total renal FSA were determined using unbiased stereologic techniques. RESULTS:
      In F1 offspring, blood pressure levels were midway between the SHR and WKY rats.
      Nephron number was significantly higher in the WKY rats compared to the SHR and
      F1 offspring. However, there was no difference in nephron number between the F1
      rats and SHR and no difference in renal FSA between the three groups. In the F2
      generation, where there is random segregation of the SHR and WKY genes, there was
      no significant correlation between either nephron number and adult blood pressure
      (r2= 0.16, P= 0.11) or total renal FSA and adult blood pressure (r2= 0.02, P=
      0.58). There was a significant inverse correlation between nephron number and
      glomerular size (r2= 0.49, P= 0.0043). CONCLUSION: There is not a direct
      corollary between nephron number or renal FSA and level of blood pressure in this
      rat model.

PMID- 14717929
TI  - Evaluation of the nitric oxide production in rat renal artery smooth muscle cells
      culture exposed to radiocontrast agents.
AB  - BACKGROUND: Radiocontrast agents (RC), substances largely used in diagnostic
      procedures, present the nephrotoxicity as one of its major side effects, which
      could be due to an altered synthesis of vasodilators. The aim of the present
      study was to evaluate the nitric oxide (NO) production in rat renal artery smooth
      muscle cells primary culture (rVSMC) exposed to RC. METHODS: The cells were
      treated for 72 hours with mannitol at 10% (MT10; 600 mOsm/kg H2O) or 35% (MT35;
      2100 mOsm/kg H2O), with the nonionic iobitridol (IBT), the low-osmolality
      ioxaglate (IXG), the high-osmolality ioxitalamate (IXT), the nonionic, iso
      osmolar iodixanol (IDX), and with lipopolysaccharide (LPS). We determined the NO
      and osmolality in the cell culture media and the cellular viability. RESULTS: By
      the Griess and chemiluminescence methods, the NO was not different in MT10 and
      IDX, but decreased in MT35, IBT, IXG, and IXT when compared with the control; it
      was increased in LPS and also decreased in all RC+LPS when compared with LPS.
      MT35, IXT, and IXT+LPS decreased the cellular viability, and the media osmolality
      was increased in MT35 and IXT compared with the control. CONCLUSION: The RC
      (except IDX) significantly reduced NO in rVSMC, which was more pronounced after
      IXT treatment (57.3%). This was not related to the reduced cell viability (15.8%)
      or to its high osmolality, because in MT35, with similar osmolality as IXT, NO
      decreased only 11.0% relatively to the control. Neither the media osmolality nor
      the cell viability was altered by IXG or IBT. The decreased NO could explain the
      vasoconstriction and, therefore, the acute renal failure by RC.

PMID- 14717930
TI  - Body mass index, dialysis modality, and survival: analysis of the United States
      Renal Data System Dialysis Morbidity and Mortality Wave II Study.
AB  - BACKGROUND: The impact of obesity on survival in end-stage renal disease (ESRD)
      patients as related to dialysis modality (i.e., a direct comparison of
      hemodialysis with peritoneal dialysis) has not been assessed adjusting for
      differences in medication use, follow-up > or =2 years, or accounting for changes
      in dialysis modality. METHODS: We performed a retrospective cohort study of the
      United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Wave II
      Study (DMMS) patients who started dialysis in 1996, and were followed until
      October 31 2001. Cox regression analysis was used to model adjusted hazard ratios
      (AHR) for mortality for categories of body mass index (BMI), both as quartiles
      and as > or =30 kg/m2 vs. lower. Because such a large proportion of peritoneal
      dialysis patients changed to hemodialysis during the study period (45.5%), a
      sensitivity analysis was performed calculating survival time both censoring and
      not censoring on the date of change from peritoneal dialysis to hemodialysis.
      RESULTS: There were 1675 hemodialysis and 1662 peritoneal dialysis patients.
      Among hemodialysis patients, 5-year survival for patients with BMI > or =30 kg/m2
      was 39.8% vs. 32.3% for lower BMI (P < 0.01 by log-rank test). Among peritoneal
      dialysis patients, 5-year survival for patients with BMI >/=30 kg/m2 was 38.7%
      vs. 40.4% for lower BMI (P > 0.05 by log-rank test). In adjusted analysis, BMI >
      or = 30 kg/m2 was associated with improved survival in hemodialysis patients (AHR
      0.89; 95% CI 0.81, 0.99; P= 0.042) but not peritoneal dialysis patients (AHR =
      0.99; 95% CI, 0.86, 1.15; P= 0.89). Results were not different on censoring of
      change from peritoneal dialysis to hemodialysis. CONCLUSION: We conclude that any
      survival advantage associated with obesity among chronic dialysis patients is
      significantly less likely for peritoneal dialysis patients, compared to
      hemodialysis patients.

PMID- 14717931
TI  - The apolipoprotein(a) size polymorphism is associated with nephrotic syndrome.
AB  - BACKGROUND: The atherogenic serum lipoprotein(a) [Lp(a)] is significantly
      elevated in patients with nephrotic syndrome. The underlying mechanism for this
      elevation is poorly understood. METHODS: We investigated in 207 patients with
      nondiabetic nephrotic syndrome and 274 controls whether the apolipoprotein(a)
      [apo(a)] kringle-IV repeat polymorphism explains the elevated Lp(a) levels in
      these patients. RESULTS: Patients showed a tremendous elevation of Lp(a)
      concentrations when compared to controls (mean 60.4 vs. 20.0 mg/dL and median
      29.8 vs. 6.4 mg/dL, P < 0.0001). Primary and secondary causes contributed to this
      elevation. The primary causes became apparent by a markedly elevated number of
      low-molecular-weight apo(a) phenotypes which are usually associated with high
      Lp(a) levels. This frequency was 35.7% in patients compared to only 24.8% in
      controls (P= 0.009). In addition, secondary causes by the pathogenetic mechanisms
      of the nephrotic syndrome itself resulted in a different increase of Lp(a) in the
      various apo(a) isoform groups. Based on the measured Lp(a) concentrations in each
      subject, we calculated separately the Lp(a) concentrations arising from the two
      expressed isoforms by estimating the relative proportion of the two serum
      isoforms in the sodium dodecyl sulfate (SDS) agarose gel electrophoresis. Low
      molecular-weight isoforms were associated with 40% to 75% elevated Lp(a)
      concentrations when compared to matched isoforms from controls. High-molecular
      weight apo(a) isoforms showed 100% to 500% elevated Lp(a) levels compared to
      matched isoforms from controls. The severity of the nephrotic syndrome as well as
      the degree of renal impairment did not influence the Lp(a) concentrations.
      CONCLUSION: The tremendously increased Lp(a) levels in nephrotic syndrome ar
      caused by primary genetic as well as disease-related mechanisms.

PMID- 14717932
TI  - Predictors of amputation and survival following lower extremity revascularization
      in hemodialysis patients.
AB  - BACKGROUND: Peripheral vascular disease (PVD) has become increasingly common in
      end-stage renal disease (ESRD) patients, leading to an increase in the rate of
      revascularization and amputation. We studied the prognosis of ESRD patients
      undergoing their first revascularization procedure. METHODS: We conducted a
      longitudinal cohort study of hemodialysis patients enrolled in special studies of
      the United States Renal Data System. Cox proportional hazards analysis was used
      to assess the independent effect of type of initial revascularization procedure
      on lower extremity amputation and all-cause, cardiac, and infectious mortality
      over 3 years, after adjustment for sociodemographic, clinical, and biologic
      baseline characteristics. RESULTS: Eight hundred patients underwent an initial
      revascularization procedure by surgical bypass or angioplasty. The overall
      incidence of subsequent amputation was 16.3/100 person-years, 22.6 for bypass,
      and 5.7 for angioplasty. After adjustment for patient characteristics, the risk
      of amputation was higher for bypass versus angioplasty [relative hazard (RH)
      4.00; 95% CI 2.46 to 6.57], for black versus white patients (RH 1.49; 95% CI 1.04
      to 2.15), for uninsured or patients on Medicaid versus patients with private
      insurance or on Medicare (RH 1.65; 95% CI 1.12 to 2.72), and for patients with
      diabetes versus no diabetes (RH 2.51; 95% CI 1.67 to 3.76). Compared with
      patients who underwent angioplasty, the risk of all-cause (RH 1.37; 95% CI 1.10
      to 1.70), cardiac (RH 1.50; 95% CI 1.08 to 2.09), and infectious (RH 2.17; 95% CI
      1.10 to 4.29) mortality was greater among patients who underwent bypass.
      CONCLUSION: Risk of amputation following revascularization procedures was
      positively associated with type of procedure, black race, uninsured/Medicaid, and
      diabetes status. Risk of death was also higher following bypass. While this might
      reflect underlying severity of disease, patient education, screening, and optimal
      care of lower extremities should be emphasized to detect PVD at an early stage of
      the disease process.

PMID- 14717933
TI  - Nocturnal blood pressure is elevated with natriuresis and proteinuria as renal
      function deteriorates in nephropathy.
AB  - BACKGROUND: We reported that patients with sodium sensitive type of hypertension
      exhibited the lack of nocturnal fall in blood pressure with enhanced natriuresis
      during night. Sodium sensitivity is caused by diminished glomerular filtration
      capability and/or augmented tubular reabsorption of sodium, and seems tightly
      linked with glomerular capillary hypertension. In the present study, we
      investigated the relationship between glomerular filtration rate and circadian
      rhythms of these parameters in patients with glomerulopathy. METHODS: Twenty six
      patients (15 men and 11 women; aged 17 to 72 years; mean age 47 +/- 3 years),
      whose diagnosis was confirmed as glomerulopathy with renal biopsy, were studied
      during hospitalization. Ambulatory blood pressure for 24 hours was monitored,
      while urinary samples were collected for both daytime (6:00 a.m. to 9:00 p.m.)
      and nighttime (9:00 p.m. to 6:00 a.m.) to estimate circadian rhythms of urinary
      sodium and protein excretion rates (UNaV, UproV). Then night/day ratios of mean
      arterial blood pressure (MAP), UNaV, and UproV were analyzed in relation to 24
      hour creatinine clearance as a marker of glomerular filtration rate. RESULTS:
      Serum creatinine and creatinine clearance were 1.1 +/- 0.1 mg/dL and 89 +/- 7
      mL/min/1.73 m2. There were significant day-night differences in MAP (96 +/- 2 mm
      Hg vs. 92 +/- 2 mm Hg; P= 0.006), UNaV (6.7 +/- 0.9 mmol/hour vs. 3.6 +/- 0.3
      mmol/hour; P= 0.003), and UproV (161 +/- 27 mg/hour vs. 128 +/- 28 mg/hour; P=
      0.02). Creatinine clearance had significantly negative relationships with
      night/day ratios of MAP (r=-0.49; P= 0.01), UNaV (r=-0.43; P= 0.03,) and UproV
      (r=-0.41; P= 0.04). In addition, night/day ratio of MAP had significantly
      positive relationships with night/day ratios of UNaV (r= 0.49; P= 0.01) and UproV
      (r= 0.45; P= 0.02). CONCLUSION: Our results show that as renal function
      deteriorates in glomerulopathy the nocturnal dip in blood pressure is lost,
      resulting in enhanced urinary sodium and protein excretions during night. These
      findings are compatible with our proposal that impaired natriuresis during
      daytime makes nocturnal blood pressure elevated to compensate for diminished
      natriuresis by pressure natriuresis. We speculate that nocturnal glomerular
      capillary hypertension contributes, at least in part, to enhanced urinary sodium
      and protein excretions during night.

PMID- 14717934
TI  - Association of hematocrit value with cardiovascular morbidity and mortality in
      incident hemodialysis patients.
AB  - BACKGROUND: Associations between hematocrit values and clinical outcome have been
      studied with conflicting results in cardiac patients, end-stage renal disease
      (ESRD) patients, and ESRD patients with cardiac disease. We studied dialysis
      patients to determine the relationship between hematocrit value and cardiac risk
      under current Dialysis Outcomes Quality Initiative (DOQI) practices. METHODS;
      Medicare data were used to study 50,579 incident hemodialysis patients selected
      from January 1, 1998, to December 31, 1999, who received hemodialysis for 9
      months after the onset of ESRD. Patients were divided into groups on the basis of
      the hematocrit value: < or =30%, >30% to < or =33%, >33% to < or =36%, >36% to <
      or =39%, and >39%. For hospitalization, the follow-up extended to 21/2 years; for
      mortality, 3 years. RESULTS: Compared to patients with hematocrit values of >33%
      to < or =36%, patients with values of >36% to < or =39% and those with values of
      >39% had risk ratios for hospitalization due to cardiac disease of 0.92 (95% CI
      0.88 to 0.97) and 0.79 (95% CI 0.72 to 0.87), respectively, and risk ratios for
      death due to cardiac disease of 0.92 (95% CI 0.87 to 0.98) and 0.83 (95% CI 0.74
      to 0.93), respectively, in the follow-up period. CONCLUSION: The significant
      associations we report do not establish a causal relationship between higher
      hematocrit values and lower risks of cardiac morbidity and mortality. A
      randomized clinical trial in low-risk patients is needed to establish causality.

PMID- 14717935
TI  - Podocyte injury associated glomerulopathies induced by pamidronate.
AB  - BACKGROUND: Pamidronate has been demonstrated to decrease bone-related
      complications in multiple myeloma and delay progression of the disease. This has
      led to its use in supportive and maintenance therapy of myeloma in conjunction
      with steroids and chemotherapy. It has also been selectively used in patients
      with breast cancer and other neoplasms. METHODS: We report on five patients who
      developed glomerular disease induced by pamidronate. Pamidronate was the only
      drug common to all patients. Tests for hepatitis B and C and human
      immunodeficiency virus (HIV) were negative for all patients. The first two
      patients received a high dose of pamidronate for 8 weeks, whereas the other three
      patients were on monthly therapy for a prolonged period of time. Sources of data
      included chart review and pathologic analysis of kidney biopsy. RESULTS: Three
      patients were female and two were males and all were Caucasian, ranging in age
      from 58 to 71 years. Renal biopsy findings included minimal change disease in
      two, focal segmental glomerulosclerosis in two, and collapsing focal segmental
      glomerulosclerosis in one. Immunofluorescence was essentially negative in all
      cases. Electron microscopy showed variable podocyte injury and extensive foot
      process effacement. There was no evidence of multiple myeloma-related renal
      disease. After the biopsy, pamidronate was discontinued and renal function
      stabilized in all patients except the one with the collapsing variant of focal
      segmental glomerulosclerosis who required hemodialysis. Three patients had
      resolution of proteinuria, one patient continued to have proteinuria without
      deterioration in renal function. CONCLUSION: Pamidronate has been mainly
      associated with collapsing focal segmental glomerulosclerosis. This report
      expands that relationship and adds other glomerular diseases linked with podocyte
      injury. Additional studies are needed to define the cause of the variability of
      renal histology with this agent.

PMID- 14717936
TI  - High dose chemotherapy in light chain or light and heavy chain deposition
      disease.
AB  - BACKGROUND: Conventional chemotherapy for myeloma yield unsatisfactory results in
      light and/or heavy chain deposition disease [(H)CDD] Because of the well
      established dose-response effect of high dose melphalan in multiple myeloma,
      aiming to dramatically reduce the pathogenic monoclonal immunoglobulin (MIg)
      level, high dose therapy is a tempting alternative approach. METHODS: We treated
      11 young patients with L(H)CDD by high dose therapy with the support of
      autologous blood stem cell transplantation. All had renal symptoms, including
      four who required dialysis and seven who had various, mainly cardiac, extrarenal
      manifestations. RESULTS: No toxic deaths occurred. A decrease in the MIg level
      was observed in eight patients, with complete disappearance from serum and urine
      in six cases. Improvement in manifestations related to MIg deposits were observed
      in six patients, including renal, cardiac, and hepatic responses in 4/11, 4/4,
      and 2/2 cases, respectively. Histologic regression of MIg deposits was documented
      in cardiac, hepatic, and skin biopsies. In contrast, examination of the kidney
      still showed light chain deposits in one patient who had renal transplantation 3
      years after high dose therapy, at a time when he was in persisting remission.
      Within a median follow-up of 51 months, three patients were retreated because of
      multiple myeloma relapse, of whom one died and one required hemodialysis, and
      renal function secondarily deteriorated in a patient who had resistant multiple
      myeloma. Otherwise, no manifestations related to MIg deposits occurred or
      recurred in any patient. CONCLUSION: Present results of this retrospective study
      argue in favor of a benefit of high dose therapy with stem cell support in young
      patients with L(H)CDD.

PMID- 14717937
TI  - Estimating the prevalence of renal insufficiency in seniors requiring long-term
      care.
AB  - BACKGROUND: Renal function declines with age, but little is known about the
      extent of renal insufficiency among the institutionalized elderly. The objective
      of this study was to estimate the prevalence of low glomerular filtration rate
      (GFR) in a large sample of elderly adults living in long-term care facilities,
      and to compare two commonly used methods for estimating GFR. METHODS: A total of
      9931 residents aged 65 years and older participated in a retrospective cross
      sectional study of 87 long-term care facilities in Ontario. GFR was estimated by
      the Cockcroft-Gault and Modification of Diet in Renal Disease Study (MDRD)
      equations. The prevalence of low GFR, using the Cockcroft-Gault equation (<30
      mL/min), was compared with the MDRD equation (<30 mL/min/1.73 m2). RESULTS: A
      total of 17.0% (95% CI 15.6 to 18.5) of men and 14.4% (95% CI 13.6 to 15.3) of
      women had a serum creatinine concentration above the laboratory reported upper
      reference limit of normal. The prevalence of both elevated serum creatinine and
      low GFR were observed to increase with age (P < 0.0001). The Cockcroft-Gault
      equation produced a consistently lower estimate of GFR than did the MDRD
      equation, a discrepancy most pronounced in the oldest residents. Among all men, a
      low GFR was more prevalent using the Cockcroft-Gault (10.3%, 95% CI 9.2 to 11.5)
      than MDRD (3.5%, 95% CI 2.8 to 4.2) equation, with a similar difference also seen
      in women (23.3%, 95% CI 22.4 to 24.3 versus 4.0%, 95% CI 3.6 to 4.5,
      respectively). Of all residents whose Cockcroft-Gault estimated GFR was under 30
      mL/min, 14.7% (95% CI 13.2 to 16.3) were found to have GFR greater than 60
      mL/min/1.73 m2 according to the MDRD equation. CONCLUSION: Age-associated renal
      impairment is common among elderly long-term care residents, but there exists a
      clear discrepancy between the Cockcroft-Gault and MDRD equations in predicting
      GFR. Consideration should be given to medication dose adjustment, based on a
      practical estimate of GFR. However clarification is needed about which method, if
      either, is most valid among the frail elderly. Complex patient and societal
      issues surrounding advanced care directives, treatments associated with renal
      insufficiency, and, if and when to initiate dialysis, require further attention.

PMID- 14717938
TI  - Icodextrin-induced peritonitis: study of five cases and comparison with bacterial
      peritonitis.
AB  - BACKGROUND: An epidemic of aseptic peritonitis related to the presence of
      peptidoglycan contaminant in some batches of icodextrin solution (Extraneal,
      Baxter Healthcare Corporation) occurred in Europe in the first six months of
      2002. METHODS: By case-control study we examined the clinical and biologic
      features of 5 patients with icodextrin-induced peritonitis (group AP) and
      compared them with 7 patients with bacterial peritonitis (group BP) recruited in
      our clinical center between January and June 2002. RESULTS: Diagnosis of
      icodextrin-induced peritonitis was confirmed in all cases by a positive
      reintroduction test with contaminated batches of icodextrin. No recurrence was
      observed on re-exposure to icodextrin free of peptidoglycan. Skin tests were
      positive with contaminated icodextrin in 2 of 5 patients, while they were
      negative with icodextrin solution free of peptidoglycan (<0.6 ng/mL). During
      peritonitis, serum level of C-reactive protein (CRP) was lower in group AP (42.4
      +/- 34 mg/L) than in group BP (135 +/- 59 mg/L) (P= 0.01). Leukocyte number in
      peritoneal dialysis effluent was lower in group AP (284 +/- 101/mm3), with a
      lower neutrophil/monocyte ratio (N/M = 0.67) than in group BP (1410 +/- 973/mm3;
      N/M = 4) (P < 0.05). A low number of peritoneal fluid eosinophilia (11 +/- 8%)
      was detected in group AP. CONCLUSION: Icodextrin-induced peritonitis was
      associated with a burst of intraperitoneal cytokines. The phenotype of peritoneal
      neutrophils was different between aseptic and bacterial peritonitis, indicating
      that inflammatory stimuli that activate neutrophils in both types of peritonitis
      are clearly distinct. Finally, peritoneal injury measured by weight gain,
      peritoneal permeability, and CA125 concentration seemed to be less severe during
      icodextrin-induced peritonitis than during bacterial peritonitis.

PMID- 14717939
TI  - Impact of nocturnal hemodialysis on the variability of heart rate and duration of
      hypoxemia during sleep.
AB  - BACKGROUND: Nocturnal hemodialysis (NHD) alleviates uremia-related sleep apnea, a
      condition characterized by increased sympathetic activity and diminished heart
      rate (HR) variability. We tested the hypothesis that NHD reduces both hypoxemia
      and sympathetic neural contributions to HR variability during sleep. METHODS:
      Episodes of apnea and hypopnea and the duration of nocturnal hypoxemia during
      sleep were determined in 9 end-stage renal disease (ESRD) patients (age: 44 +/-
      2) (mean +/- SEM) before and after conversion from conventional hemodialysis
      (CHD) to NHD, and in 10 control subjects (age: 45 +/- 3) with normal renal
      function and without sleep apnea. Low frequency (LF) (0.05-0.15 Hz) and high
      frequency (HF) (0.15-0.5 Hz) HR spectral power during stage 2 sleep was
      calculated (Fast Fourier transformation). Patients were studied 4 times (1 day
      before and on the night after their CHD session) and 6-15 months after conversion
      to NHD, while receiving NHD and on a non-dialysis night. RESULTS: NHD decreased
      the frequency of apnea and hypopnea (from 29.7 +/- 9.3 to 8.2 +/- 2.0 episodes
      per hour, P= 0.02), and duration of nocturnal hypoxemia (from 13.9 +/- 5.2 to 2.6
      +/- 1.9% of total sleep time, P= 0.02). As CHD recipients, ESRD patients had
      faster nocturnal heart rates (79 +/- 2 vs. 58 +/- 1 min-1, P= 0.03) and lower HF
      (vagal) (78 +/- 27 vs. 6726 +/- 4556 ms2, P= 0.001) spectral power than control
      subjects. After conversion to NHD, HR fell (from 79 +/- 2 to 66 +/- 1 min-1, P=
      0.03) and HF power increased (from 78 +/- 27 to 637 +/- 139 ms2, P= 0.001). The
      HF/HF+LF ratio, an index of vagal HR modulation, was lower during CHD (0.16 +/-
      0.03 vs. 0.42 +/- 0.05 in control subjects, P < 0.05) and increased (to 0.45 +/-
      0.05, P < 0.001) after conversion to NHD. The LF/HF ratio, a representation of
      sympathetic HR modulation, which was significantly higher during CHD than in
      control subjects (2.77 +/- 0.82 vs. 0.71 +/- 0.11, P < 0.05), was also normalized
      by NHD (0.74 +/- 0.12, P < 0.05, compared with CHD). CONCLUSION: Higher heart
      rates and impaired vagal and augmented sympathetic HR modulation during sleep in
      ESRD patients are normalized by NHD. Potential mechanisms for these observations
      include attenuation of surges in sympathetic outflow elicited by apnea and
      hypoxia during sleep, normalization of nocturnal breathing patterns that
      influence HRV, and removal, by increased dialysis, of a sympatho-excitatory
      stimulus of renal origin.

PMID- 14717940
TI  - Anticoagulant efficacy of PEG-Hirudin in patients on maintenance hemodialysis.
AB  - BACKGROUND: Heparins are currently the anticoagulants of choice in long-term
      hemodialysis (HD). Because of their shortcomings, including the increasing
      incidence of heparin-induced thrombocytopenia (HIT II), alternative
      anticoagulation is necessary. The study objectives were to provide safe and
      effective HD by investigating an appropriate PEG (polyethylene glycol)-Hirudin
      dosage regimen in patients on HD, as well as to compare the safety, tolerability,
      and efficacy of PEG-Hirudin with that of unfractionated heparin (UFH). METHODS:
      Twenty patients (12 males, 8 females, mean age 57.8 years) with end-stage renal
      disease (ESRD) took part in the study. Dialysis sessions lasting a mean of 4.3
      hours (QB 250 to 300 mL/min, QD 500 mL/min) were performed 3 times a week with a
      Gambro GFS plus 16 dialyzer. Ten patients (group I) received UFH at 3 regular
      dialysis sessions (HD1-3) followed by 5 dialysis sessions using PEG-Hirudin (HD4
      8). Another 10 patients (group II) received UFH at 3 regular dialysis sessions
      (HD1-3) followed by 10 sessions on PEG-Hirudin (HD4-13). The starting dose of PEG
      Hirudin was a single bolus injection of 80 microg/kg BW (HD4), except for the
      first patient, who received 50 microg/kg BW followed by a 12 microg/kg bolus.
      Before each of the following sessions (HD5-13), an individualized PEG-Hirudin
      dose of between 26 to 65 microg/kg body weight (BW) (mean dose 41 microg/kg BW)
      was injected. PEG-Hirudin plasma and blood concentrations derived from anti-Iia
      activity and ecarin clotting time (ECT), respectively, activated partial
      thromboplastin time (aPTT), bleeding time, and arteriovenous (AV) fistula
      compression time were investigated to calculate the pharmacokinetic parameters or
      to assess anticoagulant efficacy. RESULTS: Mean predialysis PEG-Hirudin plasma
      concentrations increased up to a maximum of 488 ng/mL in group I (HD8) and up to
      536 ng/mL in group II (HD8). Mean plasma concentrations measured at 5 minutes
      after the 1st (HD4), 5th (HD8), and 10th (HD13) PEG-Hirudin injection ranged from
      1076 to 1298 ng/mL. Mean post-dialysis plasma levels ranged from 818 to 995
      ng/mL. Mean predialysis aPTT was not affected by UFH, but was prolonged by 46 to
      56 seconds by PEG-Hirudin. Five minutes after injecting PEG-Hirudin or UFH, mean
      aPTT was prolonged to a maximum of 85 and 188 seconds, respectively. Mean post
      dialysis aPTT values ranged from 60 to 68 seconds after PEG-Hirudin and 34 to 46
      seconds after UFH. PEG-Hirudin was well tolerated; no serious adverse events or
      bleeding complications were observed. Safety assessments yielded no significant
      difference between the two anticoagulants. CONCLUSION: This pilot study confirmed
      the usefulness and tolerability of a PEG-Hirudin dose regimen consisting of a
      single, fixed bolus dose of 80 microg/kg BW injected before starting the first
      dialysis session (HD4) and followed by a dose titration period over at least 4
      sessions (HD5-8), which again was followed by a fixed maintenance dose period
      (HD9-13). On the basis of PEG-Hirudin data from patients with various degrees of
      renal insufficiency but not undergoing hemodialysis and prior recombinant-hirudin
      (r-hirudin) experience, patients were titrated into an EC-controlled dose range
      that proved to be efficacious enough to prevent clotting and safe enough to
      prevent bleeding. Due to the favorable pharmacokinetic properties of PEG-Hirudin,
      a residual anticoagulant effect is maintained in the intervals between dialysis
      sessions, and this permanent state of anticoagulation may prevent vascular access
      complications as well as other vascular events.

PMID- 14717941
TI  - Retransplantation in Alport post-transplant anti-GBM disease.
AB  - BACKGROUND: Post transplant anti-glomerular basement membrane (GBM) disease
      affects up to 5% of patients with Alport's syndrome. Defects in the COL4A5 gene
      are responsible for most cases, and alpha 5(IV)NC1 is the usual target for
      alloantibodies. Gene deletions are more commonly associated with this
      complication than are point mutations. The disease is severe in renal allografts
      and nearly always results in graft loss. METHODS: Three cases of
      retransplantation in Alport's syndrome are described here in detail. All cases
      were started on immunosuppressive therapy early in the course of their disease
      and one patient (case 2) received pre-emptive anti-T-cell therapy (Campath IH).
      Anti-GBM antibodies in these cases were investigated by standard anti-GBM enzyme
      linked immunosorbent assay (ELISA), by indirect immunofluorescence, and by
      Western blotting using collagenase-digested human GBM and recombinant type IV
      collagen NC1 domains made in insect cells. RESULTS: All cases showed early
      antibody and complement fixation to human GBM. Target alloantibodies were to
      alpha 5(IV)NC1 domain predominantly. Cases two and three gave negative results on
      standard ELISA for anti-GBM antibodies. Pathologic examination revealed
      crescentic glomerulonephritis, which was rapid in onset in case 1, blunted and
      less aggressive in case 3, and case 2 developed segmental necrosis without
      crescent formation. Neutrophilic infiltrates were an early feature in all 3
      cases. All cases are compared with a review of all retransplanted cases in the
      literature. CONCLUSION: Alport anti-GBM disease is a severe disease in
      retransplanted patients. Anti-T-cell therapy seemed to modify the pathologic
      findings but did not prevent graft loss. Longer term plasma exchange and
      mycophenolate mofetil may attenuate the illness, but in these cases did not
      prevent graft loss. Western blotting detected alloantibodies to alpha 5(IV) NC1
      domain and is more sensitive and specific for this disease than standard ELISAs.

PMID- 14717942
TI  - Dialyzer membrane type and reuse practice influence polymorphonuclear leukocyte
      function in hemodialysis patients.
AB  - BACKGROUND: Polymorphonuclear leukocyte (PMNL) production of reactive oxygen
      species (ROS) has been linked to hemodialysis (HD) associated morbidity. The
      effect of dialyzer membrane type and reuse on PMNL function has not been clearly
      defined. METHODS: The present report is a cross-sectional study undertaken in a
      cohort of patients undergoing regular HD, at enrollment into the Hemodialysis
      (HEMO) Study, to study the association between patient and dialysis-related
      factors and PMNL function. PMNL function was assessed by measuring PMA- and N
      formyl methionyl-leucyl-phenylalanine (fMLP) -induced respiratory burst, and
      phagocytic activity toward Staphylococcus aureus. RESULTS: PMNL from patients
      dialyzed with polysulphone (PS) or cuprophane (CU) membranes showed higher PMA
      induced respiratory burst activity compared with those exposed to substituted
      cellulose (cellulose acetate, cellulose triacetate, CA/CT) membranes, regardless
      of dialyzer reuse. The use of bleach as a cleansing agent during reuse was
      associated with higher PMA-induced PMNL superoxide production, as was the use of
      renalin when compared to aldehydes. In a subgroup of patients using PS dialyzers,
      reuse itself was associated with higher fMLP-induced superoxide production. The
      type of bleach-germicide combination during reuse showed that use of renalin as a
      germicide was also associated with higher PMNL phagocytosis index. The number of
      years on HD correlated inversely with PMA-induced PMNL superoxide response.
      Weaker PMNL response to fMLP was associated with greater comorbidity and poor
      functional status as quantified by Index of Coexisting Diseases (ICED) and
      Karnofsky scores, respectively. CONCLUSION: Our results indicate that dialyzer
      membrane type and the reuse process influence the oxidative response of PMNL
      among HD patients. The implications of these observations on clinical morbidity
      need to be further evaluated in prospective studies.

PMID- 14717943
TI  - The effect of maintenance immunosuppression medication on the change in kidney
      allograft function.
AB  - BACKGROUND: The optimum maintenance immunosuppression regimen for kidney
      transplant recipients is uncertain. In this study we determined the effect of
      maintenance immunosuppression medications on the rate of kidney allograft
      function loss defined by the annualized change in glomerular filtration rate
      (GFR). METHODS: We studied 40,963 first kidney only transplant recipients between
      1987 and 1996 with allograft survival of at least two years in the United States
      Renal Data System. Linear regression methods were applied to serial GFR estimates
      after transplantation to determine the annualized change in GFR. Patients were
      classified according to the type of maintenance calcineurin and purine metabolism
      inhibitor received after transplantation. Multiple linear regression was used to
      determine the independent effect of maintenance immunosuppression medications on
      the annualized change in GFR (mL/min/1.73m2/year). RESULTS: Compared to patients
      who received cyclosporine microemulsion (Neoral), a slower decline in GFR was
      observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22
      1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82
      mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared
      to patients who received Neoral, a faster decline in GFR was observed in patients
      who received the original oil-based formulation of cyclosporine (Sandimmune) (
      0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with
      unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to
      -1.95, P < 0.001). Compared to patients who received azathioprine, patients who
      received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61
      mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine
      metabolism inhibitor exposure had a faster decline in GFR (-0.61
      mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of
      patients who received a transplant after 1993, the decline in GFR was slower for
      tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI
      1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine
      treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45).
      CONCLUSION: Tacrolimus and MMF were the calcineurin inhibitor and purine
      metabolism inhibitor associated with the most favorable effects on rates of
      change in allograft function. Because most transplant recipients establish a low
      baseline level of allograft function, the effect of immunosuppression medication
      on GFR decline should be considered when selecting a maintenance
      immunosuppression regimen.

PMID- 14717944
TI  - Forearm reactive hyperemia and mortality in end-stage renal disease.
AB  - BACKGROUND: Reports on the general population indicated that decreased
      endothelial-mediated vasodilation has a prognostic impact on cardiovascular (CV)
      morbidity and mortality. Flow-dependent vasodilation of conduit arteries and
      ischemia-induced forearm reactive hyperemia are impaired in end-stage renal
      disease (ESRD). Whether deterioration of vasodilator function in ESRD patients
      has a prognostic impact has not been documented. The aim of this study was to
      determine whether the impaired forearm postischemic vasodilation is an
      independent predictor of mortality in ESRD patients, independently from CV end
      organ damages, which are usually associated with decreased vasodilatory response.
      METHODS: Common carotid artery intima-media thickness (CCA-IMT), aortic stiffness
      (pulse wave velocity-PWV), and LV mass (LVM) were determined for 78 stable ESRD
      patients on hemodialysis. Forearm postischemic vasodilation [flow debt repayment
      (FDR)] was measured by venous plethysmography. All-cause mortality served as the
      outcome variable over a median follow-up of 60 +/- 27 months. RESULTS: Twenty
      four deaths occurred (16 of CV origin). According to Cox regression adjusted for
      age, CCA-IMT, LVM, and PWV, all-cause mortality was independently associated with
      decreased FDR (RR 0.69 for every 10% increase; 95% CI 0.56-0.85; P= 0.0006) and
      increased aortic PWV (RR 1.16 for 1 m/s increase; 95% CI 1.04-1.29; P= 0.0091).
      CONCLUSION: Our data indicate that lower postischemic forearm reactive hyperemia
      is associated with all-cause mortality of ESRD patients, independently of the
      presence of end-organ damage such as LVH or arteriosclerosis.

PMID- 14717945
TI  - Treatment with intermittent calcitriol and calcium reduces bone loss after renal
      transplantation.
AB  - BACKGROUND: Bone loss occurs during the first 6 months after renal
      transplantation (RT), and corticosteroid therapy plays an important role.
      Although calcium plus vitamin D administration prevents corticosteroid-induced
      osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia.
      METHODS: This double-blind, randomized, and controlled prospective intervention
      trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the
      first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1
      year with calcium supplementation alone. The primary outcome measure was the
      change in bone mineral density (BMD) at 3 and 12 months after RT; we also
      explored whether the effect of calcitriol on BMD was different among vitamin D
      receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to
      calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both
      groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs.
      191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH)
      levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7
      +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P=
      0.08). CT patients preserved their BMD at the total hip significantly better than
      those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32
      +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the
      intertrochanter, trochanter, and Ward's triangle. Differences did not reach
      significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%)
      developed a hypercalcemic episode during the first 3 months after RT. The effect
      of CT on BMD at 3 months was more prominent in recipients with the at-risk allele
      of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements
      during 1 year, plus intermittent calcitriol for 3 months after RT, is safe,
      decreases PTH levels more rapidly, and prevents bone loss at the proximal femur;
      a more pronounced effect is seen in recipients with at least one at-risk allele
      of the VDR genotype.

PMID- 14717946
TI  - Cold ischemia and the reduced long-term survival of cadaveric renal allografts.
AB  - BACKGROUND: Prolonged cold ischemia time (CIT) is accompanied by delayed
      cadaveric renal allograft function and early allograft loss, but the effect of
      CIT on long-term allograft survival is less certain and has not been studied in
      detail. METHODS: Using data from the United Network for Organ Sharing, we
      identified 6465 patients who received a kidney-only transplant of cadaveric
      origin for the first time in 1995. We examined the effect of CIT on the 6-year
      survival of these kidneys using Cox proportional hazard analysis. RESULTS: The
      mean CIT of the kidney was 21 +/- 7 hours (mean +/- SD) and correlated with the
      serum creatinine on discharge (R= 0.20, P < 0.001) and the distance traveled by
      the kidneys (R= 0.30, P < 0.001). CIT had a significant effect on the 6-year
      allograft survival (a 10-hour increase in CIT was associated with a hazard risk
      ratio (RR) of 1.20 for graft failure (P < 0.001) that persisted (RR = 1.40, P=
      0.021) after adjusting for donor age, recipient age and race, human leukocyte
      antigen (HLA) mismatch, panel reactive antibodies, and first 6 months' rejection
      treatments. Similarly, compared to CIT category of 0 to 10 hours, the 6-year
      graft survival was progressively worse for 11 to 20 hours (RR = 1.03), 21 to 30
      hours (RR = 1.12), and, significantly so, for >30 hours (RR = 1.32; P= 0.011).
      The gain in HLA match with increasing CIT was not uniform; for instance, HLA
      match in >30 hours was lower than for 21 to 30 hours (2.4 +/- 1.5 vs. 2.7 +/-
      1.6; P < 0.001). CONCLUSION: (1) Cadaveric kidneys continue to undergo prolonged
      periods of cold ischemia; (2) prolonged cold storage is associated with longer
      distance traveled by the kidneys, but is not associated with any significant gain
      in tissue matching; and (3) prolonged cold ischemia is a significant predictor of
      long-term graft loss. Reducing prolonged cold ischemia by regional distribution
      of organs and less stringent tissue matching may reduce the persistent high rate
      of long-term loss of cadaveric renal allografts.

PMID- 14717947
TI  - Exercise capacity as a predictor of survival among ambulatory patients with end
      stage renal disease.
AB  - BACKGROUND: Exercise capacity is reduced in end-stage renal disease (ESRD).
      Exercise requires the integrated function of multiple vital organs, and low
      exercise capacity is an independent predictor of mortality in a number of
      clinical populations. We analyzed the value of exercise capacity, characterized
      as peak oxygen uptake (VO2), for predicting survival in a cohort of 175
      hemodialysis patients over a median follow-up of 39 months. METHODS: Survival
      status was determined for 175 ESRD patients who had participated in previous
      studies for which peak VO2 and other clinical data had been determined. Chi
      square and Kaplan-Meier survival analyses were performed, and a minimal model of
      factors related to mortality was developed by Cox multiple regression. RESULTS:
      There were 23 deaths during the follow-up period. Peak VO2 (>17.5 mL/min/kg) was
      a powerful predictor of survival (P= 0.009 by Kaplan-Meier). Age (<65 years),
      dialysis vintage (<39 months), pulse pressure (<54 mm Hg), and absence of
      diagnoses of diabetes or heart failure were also associated with better survival
      on univariate analyses. On multivariate analysis peak VO2 contributed
      significantly to the minimal explanatory model relating clinical variables to
      mortality (overall chi2= 25.5, P= 0.00001). CONCLUSION: Among these ambulatory
      ESRD patients, peak VO2 was a stronger predictor of survival than many
      traditional prognostic variables, some of which are subject to ceiling effects.
      Exercise capacity may thus provide incremental prognostic information concerning
      healthier ESRD patients. Because peak VO2 may be modified by exercise training,
      the potential of exercise as an intervention to improve survival is suggested.

PMID- 14717948
TI  - Urea space and total body water measurements by stable isotopes in patients with
      acute renal failure.
AB  - BACKGROUND: Knowledge of urea volume of distribution (Vurea) in patients with
      acute renal failure (ARF) is critical in order to prescribe and monitor
      appropriate dialytic treatment. We have recently shown that in ARF patients,
      Vurea estimation by urea kinetic modeling is significantly higher than total body
      water (TBW) by anthropometric estimation. However, these estimates of Vurea and
      TBW have not been validated by isotopic methods, considered as reference
      measurement standards. METHODS: In this study, we measured Vurea by [13C]urea and
      TBW by deuterium oxide (D2O) in 21 patients with ARF (14 males, 7 females, age
      62.0 +/- 10.6 years old, 83% Caucasian, 17% African American) at three different
      centers. These measurements were compared to TBW estimates from anthropometric
      and bioelectrical impedance (BIA) measurements. RESULTS: Our results show that
      Vurea by [13C]urea (51.0 +/- 11.7 L) is significantly higher than TBW estimated
      by all other methods (TBW by D2O: 38.3 +/- 9.8 L, P < 0.001; TBW by BIA: 45.7 +/-
      15.7 L, P= 0.08; TBW by Watson formula: 38.3 +/- 7.3 L, P < 0.001; TBW by Chertow
      formula: 39.3 +/- 7.8 L, P= 0.002, all versus Vurea). Despite significant
      overestimation of the absolute value and considerable variation, Vurea
      significantly correlated with TBW by BIA (r= 0.66, P < 0.01) and TBW by D2O (r=
      0.5, P= 0.04). There was also significant correlation between D2O and BIA
      determined TBW (r= 0.8, P < 0.001). CONCLUSION: In terms of useful guidelines to
      prescribe a specific dose of dialysis in patients with ARF, conventional
      estimates of TBW as surrogates for Vurea should be used with caution. We propose
      that these conventional estimates of TBW should be increased by approximately 20%
      (a factor of 1.2) to avoid significant underdialysis.

PMID- 14717949
TI  - Feasibility of applying ultrasound strain imaging to detect renal transplant
      chronic allograft nephropathy.
AB  - Chronic renal transplantation fibrosis, often termed Chronic Allograft
      Nephropathy, may progress undetected. Since renal fibrosis may be accompanied by
      a change in measurable elastic tissue properties, ultrasound strain management
      may be useful in it detection. Ultrasound strain imaging was performed for two
      subjects with renal transplants; one with normal renal function and one with mild
      renal insufficiency and biopsy demonstrated fibrosis. Subjects underwent
      ultrasound examination with application of a controlled deformation using phase
      sensitive, two-dimensional speckle tracking to evaluate internal tissue motion to
      measure tissue displacement and strain. Measurements over multiple beams for an
      equivalent deformational stress showed there was a threefold difference in renal
      cortical strain between the two subjects. These data suggest that ultrasound
      elasticity imaging may prove useful in measuring mechanical changes related to
      fibrosis with the transplant kidney.

PMID- 14717950
TI  - Erythropoietin: a potential remedy for renal tubular injury?

PMID- 14717951
TI  - HSP: helper, suppressor, protector.

PMID- 14717952
TI  - Epidemiology of microscopic polyarteritis: a 16-year study.

PMID- 14717953
TI  - Supplemented very low-protein diet in advanced CRF: is it money saving?

PMID- 14717954
TI  - Patients developing anti-Epo antibodies during rHuEpo treatment do not express a
      polymorphic variant of Epo.

PMID- 14717955
TI  - Fabry disease: kidney involvement and enzyme replacement therapy.

PMID- 14717957
TI  - Type IIB von Willebrand disease: a paradox explains how von Willebrand factor
      works.
AB  - Type IIB is a variant form of von Willebrand disease in which a structural
      abnormality of von Willebrand factor (VWF) causes enhanced binding to the
      platelet glycoprotein Ib receptor. As a consequence of this functional
      alteration, there is a decrease in the concentration of the largest VWF multimers
      in plasma, and the platelet count may be episodically decreased as a consequence
      of microaggregation. The net result is an apparent paradox, since the presence of
      a hyperfunctional adhesive molecule in blood causes a bleeding tendency. Here I
      recall how my colleagues and I managed to understand what goes on in these
      patients.

PMID- 14717958
TI  - Should glycoprotein IIb/IIIa inhibitors be used during all percutaneous coronary
      interventions? Yes.

PMID- 14717959
TI  - Should glycoprotein IIb/IIIa inhibitors be used during all percutaneous coronary
      interventions? No.

PMID- 14717960
TI  - PAI-1 and vasculopathy: the debate continues.

PMID- 14717961
TI  - Neointima formation and thrombosis after vascular injury in transgenic mice
      overexpressing plasminogen activator inhibitor-1 (PAI-1).
AB  - The controversial role of plasminogen activator inhibitor-1 (PAI-1) in neointima
      formation and restenosis was studied with the use of a vascular injury model in
      transgenic mice overexpressing murine PAI-1 (PAI-1 Tg) and in wild-type (WT)
      controls. Despite the high circulating PAI-1 levels in the PAI-1 Tg mice (52 +/-
      9.8 ng mL-1 vs. 0.76 +/- 0.17 ng mL-1 in WT mice), no significant fibrin
      deposition was observed in non-injured femoral arteries of 8- to 12-week-old
      mice. Two weeks after severe electric injury, extensive and comparable fibrin
      deposition was observed in both genotypes, despite a significantly reduced in
      situ fibrinolytic activity in arterial sections of the PAI-1 Tg mice. The
      neointimal and medial areas were similar in WT and PAI-1 Tg mice, resulting in
      comparable intima/media ratios (e.g. 0.94 +/- 0.25 and 1.04 +/- 0.17 at the
      center of the injury). Nuclear cell counts in cross-sectional areas of the
      neointima of the injured region were also comparable in arteries from WT and PAI
      1 Tg mice (224 +/- 63, 233 +/- 20), and the distribution pattern of alpha-actin
      positive smooth muscle cells was similar. These findings indicate that in a
      vascular injury model that induces extensive and persistent fibrin deposition in
      femoral arteries of mice, overexpression of PAI-1 does not affect neointima
      formation.

PMID- 14717962
TI  - What the structure of angiostatin may tell us about its mechanism of action.
AB  - Originally discovered in 1994 by Folkman and coworkers, angiostatin was
      identified through its antitumor effects in mice and later shown to be a potent
      inhibitor of angiogenesis. An internal fragment of plasminogen, angiostatin
      consists of kringle domains that are known to be lysine-binding. The crystal
      structure of angiostatin was the first multikringle domain-containing structure
      to be published. This review will focus on what is known about the structure of
      angiostatin and its implications in function from the current literature.

PMID- 14717963
TI  - Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C -->
      T variant, and the risk of myocardial infarction in young women: effect of female
      hormones on homocysteine levels.
AB  - In young women data are limited about the association between myocardial
      infarction (MI) and hyperhomocysteinemia, low folate or methylenetetrahydrofolate
      reductase (MTHFR) genotypes. The effect of oral contraceptive (OC) use on plasma
      homocysteine levels is not clear. We assessed the association between
      hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of MI, and we
      investigated the effect of OC use on homocysteine levels in controls. In 181
      patients with a first MI and 601 controls 18-49 years of age from a population
      based case-control study, non-fasting blood samples were available. The
      homozygote mutant allele (TT) was detected in 12% of the patients and in 10% of
      controls. The odds ratio (OR) for MI in TT patients compared with the wild-type
      (CC) controls was 1.3 [95% confidence interval (CI) 0.8, 2.3]. For all MTHFR
      genotypes combined, the OR for MI in the lowest quartile of folate (<5.4 nmol L
      1) compared with the highest quartile (>10.4 nmol L-1) was 3.0 (95% CI 1.7, 5.1).
      A 2-fold increased risk of MI was found in women with the TT genotype who had
      folate levels below the median of 7.4 nmol L-1 compared with CC genotype and
      folate levels above the median (OR = 2.0; 95% CI 1.0, 3.7). Mean homocysteine
      levels were 12.2 micromol L-1 in OC users and 12.3 micromol L-1 in non-users.
      Only at the 97.5 percentile (cut-off 21.0 micromol L-1) was the adjusted OR for
      higher vs. lower homocysteine levels increased by 2.8-fold (95% CI 1.2, 6.8). Low
      folate is a risk factor for MI, particularly in women with the MTHFR 677TT
      genotype. Homocysteine levels were not influenced by OC use.

PMID- 14717964
TI  - Natural history of arterial and venous thrombosis in children treated with low
      molecular weight heparin: a longitudinal study by ultrasound.
AB  - Low molecular weight heparin (LMWH) is efficacious in preventing recurrent
      thromboembolic events (TEs) in children. The efficacy of LMWH in resolving
      thrombus in children is, however, unknown and may differ from what has been
      observed in adults due to known differences in the hemostatic system. We reviewed
      the ultrasound (US) scanning reports of children treated with LMWH in order to
      determine the rate and predictors of thrombus resolution. Of 245 children
      consecutively treated for a non-cerebral TE with enoxaparin (Lovenox, Aventis
      Pharma Inc., QC, Canada) for at least 5 consecutive days, 190 (78%) had serial
      ultrasound available for analysis. The mean follow-up time was 7 months (median 3
      months, range 3 days to 6.6 years). The rate of complete thrombus resolution was
      101/190 (53%, 95% confidence interval 46.2-60.2%). On univariate analysis,
      arterial and non-occlusive thrombus had an increased rate of resolution when
      compared with venous and occlusive thrombus. Age at time of TE (neonates vs. non
      neonates), location of TE, initial treatment (unfractionated heparin vs. LMWH)
      and dose of enoxaparin were not related to outcome. On multivariate analysis,
      type of vessel (vein vs. artery) and occlusion (occlusive vs. non-occlusive
      thrombus) independently predicted outcome. In children, the rate of complete
      thrombus resolution is similar to the rate in adults. The clinical significance
      of residual abnormal vessels, specifically to the occurrence of post-thrombotic
      syndrome and for the diagnosis of recurrence, needs to be explored in prospective
      studies.

PMID- 14717965
TI  - A novel long-acting synthetic factor Xa inhibitor (SanOrg34006) to replace
      warfarin for secondary prevention in deep vein thrombosis. A Phase II evaluation.
AB  - BACKGROUND: Vitamin K antagonists for secondary prevention in patients with deep
      vein thrombosis (DVT) require monitoring and dose adjustments. The synthetic
      factor Xa inhibitor, SanOrg34006, has predictable pharmacokinetics and may be
      administered once weekly without dose adjustments. METHODS: After 5-7 days of
      enoxaparin treatment, patients with proximal DVT were randomized to receive 2.5,
      5.0, 7.5 or 10 mg of SanOrg34006 subcutaneously once weekly or warfarin (INR, 2.0
      3.0) for 12 weeks. The primary efficacy outcome was the composite of change in
      thrombotic burden, as assessed by ultrasonography and perfusion lung scanning at
      baseline and week 12 +/- 1, and clinical thromboembolic events. This outcome was
      classified as normalization, no relevant change, or deterioration. Other outcomes
      were major and other clinically relevant bleeding. RESULTS: A total of 659
      patients were randomized and treated. In 614 (93%) patients the primary efficacy
      outcome was evaluable. The rates of normalization and deterioration were similar
      in all SanOrg34006 groups (P = 0.4) and did not differ from the warfarin group.
      There was a clear dose-response for major bleeding among patients treated with
      SanOrg34006 (P = 0.003). Patients receiving 2.5 mg SanOrg34006 had less bleeding
      than did warfarin recipients (P = 0.03). CONCLUSIONS: SanOrg34006 dosed at 2.5 mg
      appears as effective as higher dosages and warfarin for secondary prevention in
      DVT and was not associated with major bleeding. Therefore, 2.5 mg of SanOrg34006
      administered subcutaneously once weekly might be a suitable alternative to dose
      adjusted oral vitamin K antagonist.

PMID- 14717966
TI  - A functional single nucleotide polymorphism in the thrombin-activatable
      fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal
      disease.
AB  - In meningococcal sepsis, disseminated intravascular coagulation with deposition
      of fibrin and formation of microthrombi occurs in various organs and enhanced
      inhibition of fibrinolysis is associated with adverse outcome. Recently, TAFI
      (thrombin-activatable fibrinolysis inhibitor) was identified as a link between
      coagulation and fibrinolysis, as TAFI can be activated by thrombin and once
      activated potently attenuates fibrinolysis. On the basis of this one would
      predict that DNA polymorphisms that increase TAFI activity would deteriorate the
      outcome in meningococcal sepsis. Therefore, we studied the prevalence of the
      Thr325Ile dimorphism in the TAFI gene, which is associated with increased TAFIa
      stability and activity in 50 patients who survived meningococcal disease, in 176
      first-degree relatives of a consecutive patient series with meningococcal disease
      and 212 controls from the same geographic region. The TAFI 325 Ile/Ile genotype
      was slightly more common among parents of patients with meningococcal disease
      than in controls (11% vs. 7.1%, P= 0.24). This difference was pronounced among
      the subgroup of parents of non-surviving patients (19.2%, P= 0.03). Patients
      whose parents were carriers of the TAFI 325 Ile/Ile genotype had a 1.6-fold (95%
      CI 0.7-3.7) higher risk to contract meningococcal disease and a 3.1-fold (95% CI
      1.0-9.5) increased risk to die from the infection compared with all other
      genotypes. Survivors had a genotype frequency (4.0%) that was lower than in the
      general population. TAFI 325 variants affect the outcome of meningococcal
      disease.

PMID- 14717967
TI  - Enhanced leukocyte-platelet cross-talk in Type 1 diabetes mellitus: relationship
      to microangiopathy.
AB  - BACKGROUND: Platelets and leukocytes may influence each others' function, i.e.
      platelet-leukocyte cross-talk. Diabetes mellitus (DM) is associated with platelet
      and leukocyte dysfunction. OBJECTIVE: To evaluate platelet-leukocyte cross-talk,
      and if this might contribute to platelet and leukocyte dysfunction and
      microangiopathy in DM patients. PATIENTS AND METHODS: We evaluated platelet and
      leukocyte function, and cross-talk between these cells in Type 1 DM patients
      without (n = 19) and with (n = 20) microangiopathy, and healthy subjects (n =
      27), using whole blood flow cytometry. Platelet-leukocyte cross-talk was studied
      in hirudinized whole blood incubated at 37 degrees C with stirring. RESULTS:
      Basal single platelet P-selectin and leukocyte CD11b expression were similar in
      DM patients and healthy subjects, whilst circulating platelet-leukocyte
      aggregates and plasma elastase levels were elevated in DM patients. The
      thromboxane A2 analog U46619 (3 x 10(-7) m) induced more marked increases of
      platelet P-selectin expression and platelet-leukocyte aggregation in DM patients
      than in healthy subjects. The leukocyte-specific agonist N-formyl-methionyl
      leucyl-phenylalanine (fMLP) (10(-7) m) induced more marked CD11b expression in DM
      patients with microangiopathy, compared with healthy subjects. Platelet-leukocyte
      cross-talk induced by U46619 (10(-6) m) showed no difference between DM patients
      and healthy subjects. fMLP (10(-6) m) evoked marked leukocyte activation, which
      subsequently caused mild platelet P-selectin expression. This leukocyte-platelet
      cross-talk was more pronounced in DM patients than in healthy subjects.
      Furthermore, enhanced leukocyte-platelet cross-talk was correlated to platelet
      hyperreactivity among DM patients with microangiopathy only. CONCLUSIONS: Type 1
      DM is associated with platelet and leukocyte hyperactivity, and enhanced
      leukocyte-platelet cross-talk, which may contribute to platelet hyperactivity and
      the microvascular complications seen in Type 1 DM.

PMID- 14717969
TI  - Molecular basis of severe factor XI deficiency in seven families from the west of
      France. Seven novel mutations, including an ancient Q88X mutation.
AB  - Inherited factor (F)XI deficiency is a rare disorder in the general population,
      though it is commonly found in individuals of Ashkenazi Jewish ancestry. In
      particular, two mutations--a stop mutation (type II) and a missense mutation
      (type III)--which are responsible for FXI deficiency, predominate. The bleeding
      tendency associated with plasma FXI deficiency in patients is variable, with
      approximately 50% of patients exhibiting excessive post-traumatic or postsurgical
      bleeding. In this study, we identified the molecular basis of FXI deficiency in
      10 patients belonging to six unrelated families of the Nantes area in France and
      one family of Lebanese origin. As in Ashkenazi Jewish or in French Basque
      patients, we have identified a new ancient mutation in exon 4 resulting in Q88X,
      specific to patients from Nantes, that can result in a severely truncated
      polypeptide. Homozygous Q88X was found in a severely affected patient with an
      inhibitor to FXI and in three other unrelated families, either as homozygous,
      heterozygous or compound heterozygous states. Other identified mutations are two
      nonsense mutations in the FXI gene, in exon 7 and 15, resulting in R210X and
      C581X, respectively, which were identified in three families. A novel insertion
      in exon 3 (nucleotide 137 + G), which causes a stop codon, was characterized.
      Finally, sequence analysis of all 15 exons of the FXI gene revealed three
      missense mutations resulting in G336R and G350A (exon 10) and T575M (exon 15).
      Two mutations (T575M and G350A) with discrepant antigen and functional values are
      particularly interesting because most of the described mutations are associated
      with the absence of secreted protein.

PMID- 14717968
TI  - Recombinant nematode anticoagulant protein c2, an inhibitor of tissue
      factor/factor VIIa, attenuates coagulation and the interleukin-10 response in
      human endotoxemia.
AB  - The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the
      initiation of blood coagulation under both physiological and pathological
      conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent
      inhibitor of TF/FVIIa, mechanistically distinct from tissue factor pathway
      inhibitor. The first aim of this study was to elucidate the pharmacokinetics and
      pharmacodynamics of a single intravenous (i.v.) dose of rNAPc2. The second aim
      was to study its effect on endotoxin-induced coagulation and inflammation.
      Initially, rNAPc2 was administered to healthy volunteers in three different
      doses. There were no safety concerns and the pharmacokinetics were consistent
      with previous studies, in which rNAPc2 was administered subcutaneously. rNAPc2
      elicited a dose-dependent reduction of the endogenous thrombin potential and a
      selective prolongation of prothrombin time. Subsequently, the effect on endotoxin
      induced coagulation and inflammation was studied. The administration of rNAPc2
      completely blocked the endotoxin-induced thrombin generation, as measured by
      plasma prothrombin fragment F1+2. The endotoxin-induced effect on fibrinolytic
      parameters such as plasmin-antiplasmin complexes and plasminogen activator
      inhibitor type 1 was not affected by rNAPc2. The administration of rNAPc2
      attenuated the endotoxin-induced rise in interleukin (IL)-10, without affecting
      the rise in other cytokines. In conclusion, rNAPc2 is a potent inhibitor of
      TF/FVIIa, which was well tolerated and could safely be used intravenously in this
      Phase I study in healthy male volunteers. A single i.v. dose rNAPc2 completely
      blocked endotoxin-induced thrombin generation without affecting the fibrinolytic
      response. In addition, rNAPc2 attenuated the endotoxin-induced rise in IL-10,
      without affecting the rises in other cytokines.

PMID- 14717970
TI  - Inhibition of factor VIII with a partially inhibitory human recombinant
      monoclonal antibody prevents thrombotic events in a transgenic model of type II
      HBS antithrombin deficiency in mice.
AB  - Venous thromboembolic disease is a major cause of morbidity and mortality,
      necessitating antithrombotic therapy. A human monoclonal anti-factor (F)VIII
      antibody, LCL-mAb-LE2E9, produced by a lymphoblastoid cell line derived from a
      hemophilia A patient with inhibitor to wild-type but not mutant self FVIII, was
      previously reported to achieve efficient inhibition of thrombosis in an
      experimental vena cava thrombosis model in mice. Here, the antithrombotic
      efficacy of a recombinant DNA-derived version of this anti-FVIII antibody (rec
      mAb-LE2E9) was tested in mice which carry a type II heparin binding site
      antithrombin deficiency mutation and display spontaneous chronic thrombosis in
      several sites including the penile vein of sexually active males. The recombinant
      anti-FVIII antibody (100 microg, repeated after 3 days) prevented thrombotic
      priapism in all treated males, whereas all control animals treated with saline
      (group of four animals) developed priapism within 6 days after mating (P < 0.05
      for treated vs. saline). The rec-mAb-LE2E9 and the original LCL-mAb-LE2E9 were
      equally effective (five and seven males/group, respectively). These results
      confirm that FVIII inhibition represents a potent antithrombotic strategy, and
      show that both LCL-mAb-LE2E9 and rec-mAb-LE2E9 efficiently prevent thrombosis in
      a physiological model representative of thrombosis in patients with a severe
      prothrombotic risk.

PMID- 14717971
TI  - Characterization of a tissue factor/factor VIIa-dependent model of thrombosis in
      hypercholesterolemic rabbits.
AB  - Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role
      in activating the extrinsic coagulation pathway and triggering acute coronary
      syndromes. In this study, we developed and characterized a TF-factor (F)VIIa
      mediated thrombosis model in rabbits. Balloon catheter-induced endothelial
      denudation in the femoral artery and a 4-week high cholesterol diet produced a
      localized atherosclerotic plaque at the injured site. High levels of TF mRNA and
      TF protein antigen (152 +/- 25 vs. 49 +/- 12 pg mg-1 protein in normal vessels)
      were detected in these atherosclerotic plaques. Plasma FVII coagulant activity
      (FVII:C) was significantly increased in the hypercholesterolemic rabbits (36 +/-
      1 s) compared with the normal rabbits (44 +/- 1 s, P < 0.0001). Plaque rupture
      was induced by balloon angioplasty, which resulted in thrombus formation in the
      injured vessel segment after a brief period of stasis. FVIIai, a specific TF
      FVIIa inhibitor, was administered intravenously to rabbits before plaque rupture
      at 0.3 and 1.0 mg kg-1. FVIIai dose-dependently reduced thrombus mass (14.7 +/-
      2.5 and 5.9 +/- 2.2 mg, respectively, vs. 21.6 +/- 1.9 mg in the control group).
      PD198961, a novel factor Xa inhibitor, and argatroban, a thrombin inhibitor, also
      dose-dependently inhibited thrombosis. These results indicate that thrombus
      formation in this model is initiated by the activation of TF-FVIIa pathway, which
      is attributed to TF expression in the atherosclerotic plaque and enhanced plasma
      FVII coagulant activity. This model may be useful for evaluating in vivo efficacy
      of new antithrombotic drugs, particularly TF-FVIIa inhibitors.

PMID- 14717972
TI  - Formation of tissue factor-factor VIIa-factor Xa complex promotes cellular
      signaling and migration of human breast cancer cells.
AB  - Tissue factor (TF) is a transmembrane glycoprotein that initiates blood
      coagulation when complexed with factor (F)VIIa. Recently, TF has been shown to
      promote cellular signaling, tumor growth, angiogenesis, and metastasis. In the
      present study, we examined the pathway by which TF-FVIIa complex induces cellular
      signaling in human breast cancer cells using the Adr-MCF-7 cell line. This cell
      line has high endogenous TF expression as measured by flow cytometry and
      expression of protease-activated receptors 1 and 2 (PAR1 and PAR2) as determined
      by reverse transcriptase-polymerase chain reaction analysis. Both PAR1 and PAR2
      are functionally active as determined by induction of p44/42 mitogen-activated
      protein kinase (MAPK) phosphorylation using specific agonist peptides. We found
      that MAPK phosphorylation in this cell line was strongly induced by the
      combination of FVIIa and factor (F)X, but not by FVIIa alone at a concentration
      of FVIIa that approaches physiological levels. Induction of MAPK phosphorylation
      involved the formation of TF-FVIIa-FXa complex and occurred by a pathway that did
      not require thrombin formation, indicating a critical role for FXa generation. In
      addition, induction of MAPK phosphorylation was found to be independent of PAR1
      activation. We then examined whether TF-FVIIa complex formation could promote
      tumor cell migration using a modified Boyden chamber chemotaxis assay. The
      combination of FVIIa and FX, but not FVIIa alone, strongly induced migration of
      tumor cells by a pathway that probably involves PAR2, but not PAR1 activation.
      MAPK phosphorylation was found to be required for the induction of cell migration
      by the combination of FVIIa and FX. These data suggest that TF-FVIIa-mediated
      signaling in human breast cancer cells occurs most efficiently by formation of
      the TF-FVIIa-FXa complex. One of the physiological consequences of this signaling
      pathway is enhanced cell migration that is probably mediated by PAR2, but not
      PAR1 activation.

PMID- 14717973
TI  - Whole blood clot formation phenotypes in hemophilia A and rare coagulation
      disorders. Patterns of response to recombinant factor VIIa.
AB  - Until now, no routinely used clotting assay has demonstrated the power to reflect
      significantly a patient's response to recombinant factor (rF)VIIa. Adopting a
      thrombelastographic principle, profiles of continuous whole blood (WB)
      coagulation were studied in minimally altered WB activated with a small amount of
      tissue factor (TF). Investigation of the WB clotting profile was performed before
      and after ex vivo addition of rFVIIa 20 nm to WB from 26 patients with hemophilia
      A, two patients with severe hemophilia B, and individuals with deficiencies of
      FV, FX, FXI, and FXIII. In five patients with hemophilia plus inhibitors, the
      response to ex vivo added rFVIIa and to activated complex concentrate (APCC) was
      studied. Patients with severe and moderate hemophilia A demonstrated remarkable
      variance in the hemostatic characteristics at baseline, even in groups with the
      same FVIII:C activity levels. The response to rFVIIa at 20 nm also varied
      extensively, the effect correlating with the continuous WB coagulation phenotype
      at baseline. This indicates that the efficacy of rFVIIa may be optimized by
      tailoring the dose according to the hemostatic response to varying doses tested
      prior to in vivo administration. In patients with inhibitors against FVIII and
      factor IX, rFVIIa and APCC substitution resulted in quite similar response
      patterns that appeared to be dose dependent. In severe FV, FX, and FXIII
      deficient WB, rFVIIa addition induced minor changes only. In FXI deficiency,
      rFVIIa normalized the dynamic properties of clotting, although a reduced clot
      firmness remained unchanged. In conclusion, the thrombelastographic analysis of
      WB clotting, as activated with a minute amount of TF, seems an interesting method
      that detects phenotypic variation amongst hemophilia patients. The method appears
      useful for assessment of the hemostatic capacity and it seems a promising tool
      for evaluation of the individual response to rFVIIa or APCC before and during in
      vivo administration.

PMID- 14717974
TI  - Factors influencing therapeutic efficacy and the host immune response to helper
      dependent adenoviral gene therapy in hemophilia A mice.
AB  - BACKGROUND: Adenoviral-based methods of gene therapy have been ineffective at
      providing sustained factor (F)VIII expression in outbred populations of large
      animal hemophilic models primarily due to the immunogenicity of these vectors.
      Improvements have been made in vector design leading to the development of the
      helper-dependent adenoviral (HD) system. Unfortunately, it remains unclear
      whether these modifications are sufficient to circumvent the induction of
      inhibitor formation associated with adenoviral gene transfer. OBJECTIVE: To
      develop an HD vector capable of mediating sustained FVIII expression and to
      determine the variables that influence inhibitor development. METHODS: HD vectors
      were constructed encoding the canine FVIII B-domain deleted transgene under the
      control of either the cytomegalovirus (CMV) promoter or a tissue-restricted
      hybrid element consisting of five HNF-1 binding sites, located upstream of the
      human FVIII proximal promoter. Inbred and outbred populations of hemophilic mice
      were treated, and monitored for vector-induced toxicity, therapeutic efficacy,
      and inhibitor formation. RESULTS: When HD vectors utilizing the CMV promoter were
      administered, all hemophilic mice developed high levels of FVIII inhibitors. In
      contrast, vectors under the control of the HNF/FVIII element were capable of
      achieving sustained elevations of FVIII for over 6 months. Strain-specific
      differences were also observed, with outbred animals showing a greater propensity
      towards inhibitor development in response to treatment. CONCLUSIONS: HD vectors
      can be used to provide long-term FVIII expression in hemophilic animals, but
      treatment outcome and the induction of inhibitors is dependent on a number of
      variables including the transgene promoter, the vector dose, and the genetic
      background of the host.

PMID- 14717975
TI  - G20210A is a functional mutation in the prothrombin gene; effect on protein
      levels and 3'-end formation.
AB  - BACKGROUND: The prothrombin G20210A mutation is associated with increased plasma
      prothrombin levels and risk of thrombosis. The mechanism by which this mutation
      leads to increased prothrombin expression is as yet unclear and still the subject
      of debate. OBJECTIVES: The aim of this study was to investigate the effect of the
      G20210A mutation on mRNA and protein expression. METHODS: We made a set of
      constructs containing the prothrombin 5'-regulatory region, the firefly
      luciferase reporter gene and the prothrombin 3'-UTR+ downstream region. The
      latter element contained either the 20210G or A allele and was inserted either as
      a single unit (constructs G1 and A1) or in tandem (A1A2, G1G2, A1G2, G1A2).
      Constructs were transiently expressed in HepG2 cells. Expression was evaluated by
      luciferase assays and reverse transcriptase-polymerase chain reaction (RT-PCR),
      followed by quantification of the products and determination of the ratio of
      poly(A)site usage. RT-PCR sequencing was used for determination of the actual
      site of polyadenylation in mRNAs from constructs G1 and A1 and from endogenous
      prothrombin mRNAs from HepG2 cells and human liver tissue. RESULTS: The A1
      constructs expressed 1.2-fold more protein than the G1 constructs. The double
      constructs expressed 1.4-fold more protein (A1A2 vs. G1G2). Similar results were
      found in a set of constructs in which an SV40 promoter replaced the prothrombin
      5'-regulatory region. Ratios of poly(A) site usage (expressed as ratio poly(A)
      site 1 and 2) for the tandem constructs were similar for constructs with two Gs
      or As at both poly(A)sites; 2.92 (95% confidence interval 2.39-3.45) and 2.75
      (2.55-2.95). pA1/pA2 ratios were 1.46 (1.11-1.81) for G1A2 and 6.29 (5.48-7.10)
      for A1G2 constructs with different poly(A) sites, indicating that the poly(A)site
      with the 20210A variant is favored over the normal site. In 20210G mRNAs, the G
      at 20210 was the last non-A nucleotide in the majority of mRNAs, whereas in most
      20210A mRNAs, the last non-A nucleotide was the C at 20209. Over 70% of the
      prothrombin 20210G mRNAs from HepG2 cells and human liver tissue is
      polyadenylated at position 20210. CONCLUSIONS: The 20210A variant has a more
      effective poly(A) site, leading to increased mRNA and protein expression,
      irrespective of the promoter and gene. It does not affect the position of poly(A)
      attachment.

PMID- 14717976
TI  - Factor XII-dependent increases in thrombin activity induce carboxypeptidase
      mediated attenuation of pharmacological fibrinolysis.
AB  - Activation of the contact system in patients treated with fibrinolytic agents may
      be an important source of thrombin that activates thrombin-activated fibrinolysis
      inhibitor (TAFI) and attenuates fibrinolysis. Factor (F)XIIa in plasma increased
      2-fold over 60 min in patients given either tissue plasminogen activator (t-PA)
      or streptokinase (SK). To determine whether FXIIa-mediated generation of thrombin
      and activated TAFI (TAFIa) attenuates fibrinolysis in vitro, plasma clots were
      incubated with SK (250 U mL-1) or t-PA (2.5 g mL-1) and the rate of lysis was
      measured. Plasma FXIIa impaired lysis judging from marked acceleration when 2.5
      micro m corn trypsin inhibitor were added (lysis increased by 172 +/- 144% for SK
      and 40 +/- 31% for t-PA vs. no inhibitor, n = 16, P < 0.01). Moreover, inhibition
      of thrombin with hirudin and TAFIa with carboxypeptidase inhibitor accelerated
      lysis. We conclude that activation of FXII increases thrombin generation, which
      promotes TAFIa-mediated attenuation of fibrinolysis.

PMID- 14717977
TI  - Gi-dependent and -independent mechanisms downstream of the P2Y12 ADP-receptor.
AB  - The P2Y12 ADP receptor is one of the major regulators of platelet activation and
      the target of antithrombotic thienopyridines (ticlopidine and clopidogrel). It
      has been recently cloned but the signaling pathways triggered by this receptor
      are still poorly documented. Here, we show that stimulation of the human P2Y12
      receptor stably expressed in Chinese hamster ovary cells activates two major
      intracellular signaling mechanisms leading either to cell proliferation or to
      actin cytoskeleton reorganization. Both effects were blocked by the active
      metabolite of clopidogrel, a specific antagonist of P2Y12. The P2Y12-mediated
      stimulation of proliferation required the pertussis toxin-sensitive activation of
      PI3-kinase/Akt upstream of MAP-kinases. A partial contribution of a
      transactivation mechanism, through the tyrosine kinase receptor platelet-derived
      growth factor (PDGF)-R-beta, was also observed. Conversely, the P2Y12-mediated
      reorganization of the actin cytoskeleton was Gi-independent, requiring activation
      of RhoA and Rho-kinase. Our results provide new insights into the molecular basis
      of P2Y12-mediated intracellular signaling. These data may prove to be useful for
      a better understanding of the physiological role of P2Y12, particularly in
      platelets and glial cells which express this important therapeutic target.

PMID- 14717978
TI  - Different effects of abciximab and cytochalasin D on clot strength in
      thrombelastography.
AB  - Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a
      platelet component. To assess the magnitude of the plasmatic component,
      pharmacological approaches have been proposed to eliminate the platelet
      component. We evaluated the individual and combined effects of abciximab and
      cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and
      homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with
      abciximab or cytochalasin D or a combination of both and TEGs performed.
      Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6
      +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D
      alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when
      compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/-
      3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001)
      different after individual administration of abciximab and cytochalasin D,
      combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7
      mm, P = 0.372). In whole blood of critically ill patients or patients undergoing
      major surgery there was also a significant difference of MA between abciximab
      alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7
      mm, P < 0.001). This indicates that in contrast to individual administration of
      abciximab or cytochalasin D, a combination of both compounds eliminates the
      platelet-specific effect on MA of TEG tracings.

PMID- 14717979
TI  - Differential response of platelets to chemokines: RANTES non-competitively
      inhibits stimulatory effect of SDF-1 alpha.
AB  - BACKGROUND: Among the chemokines related to CXC and CC receptor groups and
      released from platelets, leukocytes and endothelial cells, SDF-1, TARC and MDC
      have been found to be platelet agonists. Platelets do not contain SDF-1 alpha. In
      contrast, RANTES is constitutively present in platelet alpha-granules and
      released upon platelet activation. OBJECTIVES: To study a possible role of RANTES
      as a modulator of SDF-1 alpha effect on platelets, in relation to CXCR4 and
      various CC receptors. METHODS: CXCR-4 (CXCL12) receptor expression and platelet
      activation were evaluated by flow cytometry, platelet deposition was studied by
      cone and plate(let) analyzer, and platelet aggregation by turbidometric
      aggregometry. RESULTS: Flow cytometry studies revealed similar expression of CXCR
      4, the specific receptor of SDF-1 alpha on intact, inactivated, and activated
      platelets. Preincubation of platelets with RANTES affected neither CXCR-4
      expression, nor SDF-1 alpha binding to the platelet membrane. In the presence of
      fibrinogen, SDF-1 alpha activated gel-filtered platelets. RANTES did not activate
      platelets, but substantially (by 70%) inhibited SDF-1 alpha-induced fibrinogen
      binding. Similarly, RANTES abrogated the promoting effect of SDF-1 alpha on whole
      blood platelet adhesion to endothelial cell monolayer under venous flow
      conditions. In platelet-rich plasma, RANTES moderately inhibited SDF-1 alpha
      induced platelet aggregation, while it did not affect aggregation induced by
      thrombin-receptor activation peptide, adenosine diphosphate, or phorbol 12
      myristate 13-acetate. A synergistic inhibitory effect of RANTES and prostaglandin
      E1 used at subthreshold concentrations, on SDF-1 alpha-induced aggregation and
      SDF-1 alpha-induced fibrinogen binding to platelets was observed, which may
      suggest involvement of RANTES in a cAMP-dependent signal transduction pathway.
      CONCLUSIONS: RANTES non-competitively inhibits activation of platelets by SDF-1
      alpha, and thus may play a regulatory role in platelet response to inflammation.

PMID- 14717980
TI  - von Willebrand factor binding to platelet glycoprotein Ib-IX-V stimulates the
      assembly of an alpha-actinin-based signaling complex.
AB  - BACKGROUND: Pathological shear stress induces platelet aggregation that is
      dependent on von Willebrand factor (VWF) binding to glycoprotein (Gp)Ib-IX-V and
      phosphatidylinositol 3-kinase activation. We tested the hypothesis that
      pathological shear stress stimulates phosphatidylinositol 3,4,5-trisphosphate
      (PIP3) synthesis by directing the assembly of a molecular signaling complex that
      includes class IA phosphatidylinositol 3-kinase (PI 3-KIA). METHODS: Platelets
      were subjected to 120 dynes cm-2 shear stress in a cone-plate viscometer. Resting
      and sheared platelets were lyzed, immunoprecipitations of PI 3-KIA performed, or
      lipids extracted for PIP3 measurements. alpha-Actinin was incubated with
      phosphatidylinositol 4,5-bisphosphate (PIP2), immunoprecipitated, and used as a
      substrate for in vitro PI 3-KIA activity. RESULTS: Pathological shear stress
      induces biphasic PIP3 production. In resting platelets, PI 3-KIA associates with
      alpha-actinin and PIP2. After exposure to shear stress, alpha-actinin and PIP2
      rapidly disassociate from PI 3-KIA. PI 3-KIA then gradually re-associates with
      PIP2 and alpha-actinin, and this complex becomes linked to GpIb alpha through the
      cytoskeleton. PIP3 production and the observed changes in the association between
      alpha-actinin, PIP2, and PI 3-KIA are inhibited when VWF binding to GpIb alpha is
      blocked. In a cell-free system, alpha-actinin binds PIP2 and when the alpha
      actinin-PIP2 complex is added to platelet PI 3-KIA, PIP3 production is
      stimulated. CONCLUSIONS: These results suggest that pathological shear-induced
      VWF binding to GpIb-IX-V stimulates PIP3 production through the assembly of an
      alpha-actinin-based complex that colocalizes PI 3-KIA with substrate PIP2.

PMID- 14717981
TI  - Fibrin polymerization is crucial for thrombin generation in platelet-rich plasma
      in a VWF-GPIb-dependent process, defective in Bernard-Soulier syndrome.
AB  - Defective prothrombin consumption has been reported in the proband case of
      Bernard-Soulier syndrome (BSS). There is no consensus, however, on whether the
      formation of platelet procoagulant activity (PPA) is impaired in BSS and, if so,
      whether this is due to the lack of GPIb-V-IX-dependent binding of thrombin or of
      von Willebrand factor (VWF). We show thrombin generation (TG) in platelet-rich
      plasma of BSS (BSS-PRP) to be defective provided that fibrin remains present in
      the reaction mixture and that the giant platelets are not damaged by frequent
      subsampling. In BSS-PRP addition of (thrombin-free) fibrin did not increase TG as
      in normal PRP, supporting our previous hypothesis that the interaction of fibrin,
      VWF and GPIb triggers PPA development. Fibrin formed during the lag phase of TG
      by a snake venom enzyme which only removed fibrinopeptide A induced an immediate
      burst of TG, that was inhibited by a monoclonal antibody against GPIb (6D1) that
      abolishes ristocetin-induced binding of VWF to platelets. Inversely, inhibition
      of polymerization decreased TG and the residual activity was insensitive to 6D1.
      We conclude that polymerizing fibrin interacts with VWF so as to activate GPIb.

PMID- 14717982
TI  - Activation of integrin alpha IIb beta 3 in the glycoprotein Ib-high population of
      a megakaryocytic cell line, CMK, by inside-out signaling.
AB  - Affinity/avidity state of integrin alpha IIb beta 3 is regulated by intracellular
      inside-out signaling. Although several megakaryocytic cell lines have been
      established, soluble ligand binding to alpha IIb beta 3 expressed in these cells
      by cellular agonists has not been demonstrated. We have re-examined agonist
      induced alpha IIb beta 3 activation on megakaryocytic cell lines with a marker of
      the late stage of megakaryocytic differentiation, glycoprotein Ib (GPIb).
      Activation of alpha IIb beta 3 was assessed by PAC1 and soluble fibrinogen
      binding to the cells. We found that alpha IIb beta 3 expressed in CMK cells with
      high GPIb expression was activated by a phorbor ester, phorbol myristate acetate
      (PMA). Although the population of the GPIbhigh cells was <0.5% of the total
      cells, incubation with a nucleoside analog, ribavirin, efficiently increased the
      PMA-reactive GPIbhigh cells. Not only PMA but also a calcium ionophore, A23187,
      induced alpha IIb beta 3 activation, and PMA and A23187 had an additive effect on
      alpha IIb beta 3 activation. Ligand binding to the activated alpha IIb beta 3 in
      the GPIbhigh CMK cells is totally abolished by an alpha IIb beta 3-specific
      antagonist, and inhibited by wortmannin, cytochalasin-D and prostaglandin E1, and
      the effects of these inhibitors on alpha IIb beta 3 activation in the GPIbhigh
      CMK cells were compatible with those in platelets. We have also demonstrated that
      the ribavirin-treated CMK cells express PKC-alpha, -beta, -delta and -theta, and
      suggested that PKC-alpha and/or -beta appear to be responsible for PMA-induced
      activation of alpha IIb beta 3 in CMK cells.

PMID- 14717984
TI  - Dr Leandro Tocantins's inhibitor theory of hemophilia and factor X: reply.

PMID- 14717985
TI  - Immune reconstitution inflammatory syndrome (IRIS) as a cause for inhibitor
      development in hemophilia.

PMID- 14717986
TI  - A randomized, double-blind, placebo-controlled clinical trial of high-dose
      interferon-alpha induction treatment combined with ribavirin for chronic
      hepatitis C in hemophilia.

PMID- 14717987
TI  - An informed consent form for treatment with oral anticoagulants.

PMID- 14717988
TI  - The bleeding tendency in patients with low von Willebrand factor and type 1
      phenotype is greater in the presence of impaired collagen-induced platelet
      aggregation.

PMID- 14717989
TI  - Soluble thrombomodulin in patients with established atherosclerosis.

PMID- 14717990
TI  - Psychological factors and cardiovascular disease.

PMID- 14717991
TI  - Platelet-derived sphingosine 1-phosphate induces contraction of coronary artery
      smooth muscle cells via S1P2.

PMID- 14717992
TI  - The factor VIII gene intron 1 inversion mutation: prevalence in severe hemophilia
      A patients in the UK.

PMID- 14717994
TI  - Fetal alcohol syndrome: diagnosis, epidemiology, and developmental outcomes.
AB  - In Australia the issue of fetal alcohol syndrome (FAS) has not been the subject
      of policy development or of extensive research. There is a lack of knowledge,
      both in the general community and by health professionals, of the nature of the
      risks associated with heavy alcohol consumption during pregnancy and the factors
      that increase this risk. This paper reviews the literature surrounding FAS with
      the aim of providing the reader an understanding of the diagnostic features and
      epidemiology of FAS and of the developmental sequelae associated with this
      syndrome.

PMID- 14717995
TI  - FAS in Australia: fact or fiction?

PMID- 14717996
TI  - Slight and mild hearing loss in primary school children.
AB  - Although slight/mild sensorineural hearing loss affects about 3% of the school
      aged population, with many more children having such impairments at single
      frequencies or in only one ear, little is known about its impacts on language,
      learning, and quality of life. This annotation explores what is known about
      prevalence and impact of this condition and argues for large-scale research to
      better address these issues.

PMID- 14717997
TI  - Perinatal mortality audit.

PMID- 14717998
TI  - Perinatal mortality 1982-2001 at Vila Central Hospital, Vanuatu.
AB  - OBJECTIVE: To determine the perinatal mortality at Vila Central Hospital (VCH)
      and thereby make an estimate of Vanuatu's perinatal mortality. METHODS: Labour
      floor and nursery records from VCH, Vanuatu's only tertiary referral hospital,
      were examined and collated for the period 1982-2001. Death certificate books were
      also examined. The perinatal mortality rate was calculated as the sum of
      stillbirths (infants = 20 weeks and/or = 500 g) and neonatal mortality (deaths
      <28 days). Premature infants were recorded for infants less than 37 weeks
      gestation and small-for-gestational-age for infants less than 2500 g. RESULTS:
      The mean perinatal mortality rate for the period was 27/1000, (range 15-36/1000).
      The mean stillbirth rate was 15/1000, (range 8-22/1000). The neonatal mortality
      was 12/1000, (range 4-18/1000). Premature babies accounted for 37/1000 births,
      (range 11-80/1000). Small-for-gestational-age infants were recorded in 45/1000
      births, (range 16-83/1000). The mean twinning rate was 12/1000. Seven spontaneous
      triplets, two quadruplets and two pairs of siamese twins were born. Sepsis,
      meconium aspiration and birth asphyxia were the commonest causes of neonatal
      death. CONCLUSION: Accurate data collection is difficult in Vanuatu. There is the
      risk of under-ascertainment however, the figure of 27/1000 represents the current
      best possible estimate of perinatal mortality at VCH over the last 20 years. VCH
      is Vanuatu's premier hospital and it is likely that the national figure for
      perinatal mortality is higher, probably in the range of 37-39/1000. This places
      Vanuatu's perinatal mortality at a level 30 years or more behind Australia. These
      figures represent the largest account of hospital based perinatal data collected
      from any Pacific island nation.

PMID- 14717999
TI  - Memory function in childhood epilepsy syndromes.
AB  - OBJECTIVE: Children with epilepsy are at risk of specific cognitive deficits. We
      aimed to compare and characterize the memory function of children with childhood
      absence epilepsy (CAE), frontal lobe epilepsy (FLE) and temporal lobe epilepsy
      (TLE). METHODS: Epilepsy syndrome was identified by clinical data, seizure
      semiology, interictal and ictal electroencephalogram (EEG). Seventy children aged
      6-18 years with CAE, FLE or TLE had neuropsychological assessment including
      memory function. After adjusting for epilepsy variables, neuropsychological
      results of the syndrome groups and normative data were compared. RESULTS:
      Children from all three syndrome groups were at risk of memory difficulties. The
      duration of epilepsy correlated negatively with memory function. Children with
      TLE had the worst memory function, significantly lower in verbal memory tasks
      than children with CAE (P = 0.02) and children with FLE (P = 0.01). The
      performance of children with TLE was significantly below the normed mean across
      all verbal and most visual tasks. Compared to the normed means, children with FLE
      had results that were statistically lower in some verbal and visual tasks, and
      children with CAE were lower in two visual tasks only. CONCLUSIONS: This study
      demonstrates memory dysfunction in three common childhood epilepsy syndromes.
      Children with TLE had the greatest impairment, children with FLE had memory
      difficulties not previously reported, and children with CAE had subtle memory
      deficits. Qualitative differences were also evident. Longer duration of
      intractable epilepsy was associated with reduced memory ability. Memory function
      and its potential impact on academic achievement are vital considerations when
      managing children with epilepsy.

PMID- 14718000
TI  - Clinical profile of children with nephrotic syndrome not on glucorticoid therapy,
      but presenting with infection.
AB  - OBJECTIVE: This is a prospective, hospital based study over a period of one year,
      to examine the clinical profile of nephrotic children not on glucocorticoid
      therapy, but presenting with infection. METHODS: Sixty-eight children with 76
      episodes of nephrotic syndrome were enrolled during the study year. They were
      examined for evidence of infection using clinical and investigative criteria. The
      children were monitored daily for proteinuria and improvement of infection. After
      the infection was controlled, prednisolone therapy was started in those who were
      not already in remission. RESULTS: Of the 76 episodes, eight were excluded from
      analysis as they had developed infection while they were on glucocorticoid
      therapy. Of the remaining 68 nephrotic episodes in 60 children, there was
      evidence of infection in 57 episodes (83.8%). Upper respiratory infection was the
      most common (28.0%) followed by urinary tract infection (22.8%), peritonitis
      (15.8%), pneumonia (14.0%), acute invasive diarrhoea (10.5%) and empyema (5.3%).
      Children with infection had significantly lower serum albumin and higher serum
      cholesterol compared to non-infected children. Of the 57 episodes with infection,
      remission occurred with control of infection alone in nine episodes (15.8%) and
      glucocorticoid therapy was not required. CONCLUSION: Infection is widely
      prevalent among Indian children presenting with episodes of nephrotic syndrome,
      even when they are not on glucocorticoid therapy. Some children may go into
      remission by control of infection alone. Among the infections, upper respiratory
      and urinary tract infections are the most common.

PMID- 14718001
TI  - Changes in body mass index in 11-12-year-old children in Hawkes Bay, New Zealand
      (1989-2000).
AB  - OBJECTIVE: To describe and compare the body mass index (BMI; weight/height2)
      profile of 11-12-year-old children in Hawkes Bay, New Zealand in 1989 and 2000.
      To subsequently determine the prevalence of overweight and obesity at the two
      time points using international definitions. METHODOLOGY: As part of asthma
      prevalence studies in Hawkes Bay data on height, weight and ethnicity were
      collected from 871 school children in 1989, and 894 children in 2000 who reached
      12 years of age during the year of testing. RESULTS: In the total study
      population the geometric mean BMI increased from 18.1 kg/m2 (95% CI 17.9; 18.3)
      in 1989 to 19.8 kg/m2 (95% CI 19.6; 20.0) in 2000, a relative increase of 9.2%
      (95% CI 7.6; 10.9), P < 0.001. Significant relative increases were found for
      males (9.0%: 95% CI 6.8; 11.3), females (9.3%: 95% CI 6.8; 11.8), Maori (7.6%:
      95% CI 4.3; 11.1), European (9.1%: 95% CI 7.3; 11.0) and Pacific Island children
      (11.0%: 95% CI 2.2; 20.5). In 2000 20.9% of Hawkes Bay children were classified
      as overweight and 9.1% as obese. The risk of being overweight in 2000 was 2.2
      times greater than the risk in 1989, and the risk of being obese was 3.8 times
      greater, with these problems more pronounced among Maori (overweight 24.7%, obese
      15.3%) and Pacific Island (overweight 35.0%, obese 15.0%) than European
      (overweight: 18.2%, obese 5.7%) children. However, the risk of being overweight
      (RR = 3.0, 95% CI 2.2-4.0) or obese (RR = 8.3, 95% CI 3.0-23.3) in 2000 compared
      to 1989 was greater among European children. CONCLUSION: Higher percentages of
      Maori and Pacific Island children are overweight or obese compared to European,
      but in all ethnic groups there has been a statistically significant increase in
      mean BMI over an 11-year period. This increase reflects the trend observed in
      other developed countries and underlines childhood obesity as a major health
      problem in New Zealand.

PMID- 14718002
TI  - Outcomes for infants weighing less than 1000 grams cared for with a nasal
      continuous positive airway pressure-based strategy.
AB  - OBJECTIVE: To compare outcomes for infants weighing less than 1000 g treated with
      a predominantly nasal continuous positive airways pressure (CPAP) approach
      (modelled on that of Columbia University, New York) with outcomes audited by the
      Australian and New Zealand Neonatal Network (ANZNN). METHODS: Data on all infants
      weighing less than 1000 g admitted for intensive care were collected
      prospectively for the 29 neonatal units contributing to the ANZNN database.
      Outcomes for infants treated at Middlemore Hospital over a 3-year period (1998
      2001) were compared with the ANZNN data for 1999. RESULTS: Sixty-four infants
      were admitted to Middlemore Hospital and 954 to the other 28 neonatal units. The
      two groups were similar with respect to birthweight, Apgar scores, sex and
      delivery method. Gestational age was lower in the Middlemore infants and outcome
      variables were adjusted for this difference. Fewer babies at Middlemore were born
      to mothers who had completed antenatal corticosteroids. The Middlemore Hospital
      group spent longer on CPAP (P < 0.001) but had less time in oxygen (median 4 days
      compared to 54 days; P < 0.001). Fewer of the Middlemore cohort were in oxygen at
      both 28 days (odds ratio 0.17 with 95% CI 0.09-0.30) and 36 weeks corrected
      gestation (odds ratio 0.15 95% CI 0.07-0.32) and fewer infants were discharged
      home on oxygen (odds ratio risk 0.38 95% CI 0.16-0.90). Other outcomes were a
      reduction in the number of infants with culture proven sepsis at Middlemore
      Hospital but a higher rate of necrotizing enterocolitis. Length of hospital stay
      and survival rates were not significantly different. CONCLUSIONS: Improved
      respiratory outcomes for infants weighing less than 1000 g were evident at
      Middlemore Hospital. This was attributed to the use of a nasal CPAP-based
      respiratory support system.

PMID- 14718003
TI  - Lack of plasma leptin response to feeding in newborn infants.
AB  - OBJECTIVE: Previous reports of the postprandial regulation of leptin are
      controversial, and there have been few studies on the effects of breast-feeding
      on postprandial regulation in newborn infants. We examined the response of plasma
      leptin to breast- and formula-feeding in newborn infants. METHODS: We measured
      the plasma leptin levels using an enzyme-linked immunosorbent assay kit before
      and after feeding in 12 breast-fed and 11 formula-fed mature infants. RESULTS:
      There was no significant difference in plasma leptin levels in breast-fed infants
      before and after feeding or in artificially fed infants before and after feeding.
      CONCLUSION: Our results suggest that feeding does not play a role in the acute
      response of circulating leptin levels in either breast- or formula-fed infants.

PMID- 14718004
TI  - Improved folate status in children and adolescents during voluntary fortification
      of food with folate.
AB  - OBJECTIVE: To assess longitudinal changes in folate status in South Australian
      children and adolescents during fortification of food with folic acid. METHODS:
      Sixty-nine children and adolescents (age 12.8 +/- 2.3 years), 47 with diabetes
      and 22 healthy controls, had their folate status assessed at the beginning of
      1999 and again after a mean 1.1 +/- 0.23 years. Intake of folate at baseline was
      assessed with a quantitative food frequency questionnaire. RESULTS: Baseline red
      cell folate (mean +/- standard deviation (SD)) was 756 +/- 294.5 nmol/L and
      remained constant at follow up at 736 +/- 299 nmol/L (P = 0.55) in the whole
      group. Serum folate increased from 24.4 +/- 6.3 nmol/L to 27.2 +/- 8.8 nmol/L (P
      = 0.002). Children with diabetes showed a significant increase in serum folate
      (from 26.3 +/- 5.7-30.1 +/- 7.9, P < 0.001) and stable red cell folate (835.8 +/-
      278.6 and 808.6 +/- 296.7, P = 0.51) between baseline and the second samples,
      while controls showed stable serum (20.4 +/- 5.7 and 21.1 +/- 7.7, P = 0.7) and
      red cell folate (586.6 +/- 255.9 and 579.8 +/- 240.1, P = 0.92). A third sample
      collected in 17 subjects after a further 9 +/- 1.3 months showed a further
      increase in serum and red cell folate. Mean folate intake at baseline was 301 +/-
      129 micro g/day, below the mean recommended for prevention of neural tube
      defects. CONCLUSIONS: Voluntary fortification of food with folate is associated
      with improved folate status in South Australian children and adolescents, but may
      not be sufficient at current levels to provide maximal protection against neural
      tube defects at a population level.

PMID- 14718005
TI  - Cephalosporin resistant urinary tract infections in young children.
AB  - OBJECTIVE: To describe the antibiotic resistance pattern of bacteria causing
      urinary tract infection (UTI) in a cohort of Australian children under 6 years of
      age. METHODS: Data were collected over a 12-month period from children under 6
      years of age with a provisional diagnosis of UTI made in the Emergency Department
      of Sunshine Hospital, Victoria. RESULTS: During the study period 100 culture
      proven UTI were identified in 97 children. Three children had two episodes. Out
      of the 100 episodes, 39% were male, 56% were under 12 months of age at
      presentation and 61% were managed as outpatients. Clinical features were non
      specific in the majority of cases. Hydronephrosis and vesicoureteric reflux was
      detected in 5.5% and 28.6%, respectively, of children with their first
      investigated UTI. A single bacterial isolate was cultured from 97 urines and two
      from three samples. Escherichia coli (n = 90) and Proteus mirabilis (n = 5) were
      the most common isolates. In vitro resistance to ampicillin/amoxycillin was found
      in 52% of isolates, to trimethoprim in 14% and to cephalothin/cephalexin in 24%.
      This resistance rate to first generation cephalosporins is the highest reported
      to date in adult or paediatric UTI in Australia. CONCLUSIONS:
      Ampicillin/amoxycillin or cephalothin/cephalexin may not be the optimal choice of
      antibiotic for the empiric treatment of UTI in this and possibly other paediatric
      populations.

PMID- 14718006
TI  - Cerebral sinus venous thrombosis in children.
AB  - OBJECTIVE: Cerebral sinus venous thrombosis (cerebral SVT) is rare in children.
      Information on clinical characteristics, radiological findings and outcome is
      emerging. METHODS: Cases of cerebral SVT diagnosed between 1995 and 2001 were
      identified by a computer-assisted search using International Classification of
      Disease codes. Medical records were reviewed to collect information on clinical
      presentation, investigations, treatment and outcome. RESULTS: Sixteen cases of
      cerebral SVT were identified. All cases presented in association with head and
      neck pathology. The majority of cases presented with symptoms of raised
      intracranial pressure and focal neurological signs. Magnetic resonance imaging
      identified all cases of cerebral SVT whilst CT scanning failed to demonstrate the
      diagnosis in two cases. Management with anticoagulation was associated with
      radiological resolution of the thrombosis and normal neurological outcome. Long
      term follow up demonstrated neurological deficits in greater than 40% of
      patients. CONCLUSION: Cerebral SVT in children is associated with significant
      residual neurological morbidity. Prospective studies to identify predictors of
      outcome and effective management interventions are required.

PMID- 14718007
TI  - A comparison between optimal and actuarial health care costs of adolescents with
      diabetes.
AB  - OBJECTIVE: To assess actuarial cost and cost of optimal standards of care for
      adolescents with type 1 diabetes in a tertiary, hospital-based care setting. To
      also assess actuarial costs of diabetic adolescents in psychosocial crisis.
      METHODS: Contact diaries were maintained over a 1-year period (June 1999-June
      2000). Contacts recorded included both structured and non-structured clinical
      encounters with contact times recorded. In addition, optimal or 'ideal' hospital
      based support and contact times for adolescents were estimated and recorded in
      minutes per year. Three illustrative cases of adolescents in psychosocial crisis
      were also assessed in terms of actuarial health care professional contact times.
      Costs were then calculated according to Victorian hospital pay structures per
      professional for 1999-2000. RESULTS: The mean and median actuarial costs of
      caring for patients aged between 10 and 19 years were 1307 Australian dollars per
      year and 515 Australian dollars per year, respectively. The cost of optimal care
      for an adolescent was estimated at 2817 Australian dollars per year after the
      first year of diagnosis. The costs per year of the three adolescents in crisis
      ranged from 10,137 Australian dollars per year to 30,524 Australian dollars per
      year. CONCLUSIONS: Cost benefits may be seen in the short term by reducing the
      number of adolescents who end up in psychosocial crisis. Current actuarial costs
      of diabetic care for adolescents falls short of an optimal standard of care.
      Diabetic adolescents who fall into psychosocial crisis consume a disproportionate
      share of a limited clinical resource.

PMID- 14718008
TI  - Congenital cyanotic heart disease and headache.

PMID- 14718009
TI  - Severe acute respiratory syndrome: 'SARS' or 'not SARS'.
AB  - Accurate clinical diagnosis of severe acute respiratory syndrome (SARS) based on
      the current World Health Organization definition is difficult and at times
      impossible at the early stage of the disease. Both false positive and false
      negative cases are commonly encountered and this could have far-reaching
      detrimental effects on the patients, their family and the clinicians alike.
      Contact history is particularly important in diagnosing SARS in children as their
      presenting features are often non-specific. The difficulty in making a correct
      diagnosis is further compounded by the lack of a sensitive rapid diagnostic test.
      Serology is not particularly helpful in the initial triaging of patients as it
      takes at least 3 weeks to become positive. Co-infection and other treatable
      conditions should not be missed and conventional antibiotics should remain as
      part of the first-line treatment regimen. We report five cases to illustrate the
      difficulties and dilemmas faced by clinicians in diagnosing SARS in children.

PMID- 14718010
TI  - Acute transverse myelitis caused by Coxsackie virus B5 infection.
AB  - A 6-year-old boy developed symptoms of rapidly progressive paraplegia, associated
      with bowel and urinary dysfunction, but without sensory loss. Magnetic resonance
      imaging (MRI) examination showed diffuse swelling of the lower spinal cord on T1
      weighted images. Based on the clinical presentation and MRI findings, a diagnosis
      of acute transverse myelitis was made. The serum titer of neutralizing antibody
      against Coxsackie virus B5 rose from 1/4 on admission to 1/256 1 month later and
      Coxsackie virus B5 was isolated from stool samples. This case serves as a
      reminder that acute transverse myelitis can be a rare clinical manifestation of
      Coxsackie virus B5 infection.

PMID- 14718011
TI  - Fatal necrotizing pneumonia caused by group A streptococcus.
AB  - Group A streptococcus (GAS) causes invasive, non-invasive and non-suppurative
      diseases. Pneumonia is one of the invasive infections caused by GAS. Although GAS
      is a significant and serious cause of childhood pneumonia, it is often overlooked
      clinically. Similarly, the recent literature is surprisingly scant on reports of
      GAS pneumonia and concentrates mainly on varicella-associated invasive GAS
      diseases. In this case report, we present a previously healthy 7-year-old child
      with community-acquired pneumonia that progressed rapidly and resulted in sepsis,
      respiratory failure and death. In both blood and pleural fluid cultures,
      Streptococcus pyogenes were isolated. On autopsy, macroscopic examination
      revealed that the lung tissue appeared to have lost its normal architecture.
      Necrosis was present and the lung had a spongy appearance with some solid areas.
      The light microscopy revealed massive oedema, haemorrhages, intense inflammatory
      cell infiltration and necrosis. This case report highlights the need for
      consideration of invasive GAS infection in the event of severe, rapidly
      progressing pneumonia in children.

PMID- 14718012
TI  - Induced septic abortion: a major factor in maternal mortality and morbidity.
AB  - BACKGROUND: Septic abortion is an infection of the uterus and its appendages
      following any abortion especially, illegally performed induced abortions. It is
      characterized by a rise of temperature to at least 100.4 degrees F, associated
      offensive or purulent vaginal discharge and lower abdominal pain and tenderness.
      AIM: To study maternal mortality and morbidity in induced septic abortions.
      METHODS: Induced septic abortions were analyzed between April 1992 and September
      1999 in TU Teaching hospital. Morbidity indicators were surgery other than
      curettage, prolonged hospitalization and permanent damage. RESULTS: In 92 cases
      of induced septic abortions, comprising 6% of total abortions; nine deaths
      occurred because of disseminated intravascular coagulation, acute renal failure
      and adult respiratory distress syndrome. Vaginal, intraperitoneal and gum
      bleeding; epistaxis and malaena resulted in severe anemia (Hb < 6 gm/L) in 11
      cases. Wound debridement and skin graft cured two cases of necrotizing fasciitis.
      One of four conservatively managed tubo-ovarian masses spontaneously drained
      rectally. In 15 cases laparotomy for pus drainage, salpingectomy, salpingo
      oophorectomy, hysterotomy/uterine rent repair was conducted, along with four
      bowel surgeries and six hysterectomies were performed. Post-operative
      complications included burst abdomen (one case) and reopened pyoperitoneum, which
      resulted fecal fistula in three cases, one of these patients died. CONCLUSION: :
      Induced abortion was proven to be a major detrimental factor for maternal
      mortality. Morbidity was four times higher than mortality to the extent that
      patients suffered hemiplegia and forced barrenness.

PMID- 14718013
TI  - Combined diagnostic approach of laparoscopy and hysteroscopy in the evaluation of
      female infertility: results of 612 patients.
AB  - AIM: To clarify the role of a combined diagnostic approach using laparoscopy and
      hysteroscopy in the evaluation of female infertility in developing countries.
      METHODS: In a prospective study, 612 consecutive infertile women underwent
      complete fertility evaluation at a tertiary university infertility clinic: 300
      complained of primary infertility, 221 of secondary infertility, and 91 were
      requesting reversal of a previous tubal ligation. All the patients were examined
      by simultaneous combined laparoscopy and hysteroscopy as a part of their routine
      infertility evaluation. Focused hysteroscopic evaluation of the region of utero
      tubal junction was attempted. RESULTS: Laparoscopy was successful in 608 and
      hysteroscopy in 597 patients. The most frequent pathologies detected
      hysteroscopically in the infertile group were adhesive in nature and believed to
      be post-traumatic and/or post-phlogistic. The number of intrauterine
      abnormalities found by hysteroscopy was significantly greater than by
      hysterosalpingography. The rate of diagnosis of significant lesions by
      laparoscopy of 64.3% rose to 76.6% when the hysteroscopic findings were included.
      A significant number of women with secondary infertility had abnormal
      hysteroscopic findings when compared to either women with primary infertility or
      those requesting sterilization reversal. Hysteroscopic evaluation of the region
      of utero-tubal junction revealed significant lesions believed to have caused
      infertility in comparison with those requesting sterilization reversal.
      CONCLUSION: The combined diagnostic approach of laparoscopy and hysteroscopy is
      recommended in the evaluation of female infertility in communities where the risk
      of pelvic infections is great.

PMID- 14718014
TI  - Fetal heart rate and uterine contraction during automobile driving.
AB  - OBJECTIVE: The purpose of this study was to clarify the influence of automobile
      driving in the third trimester of pregnancy on fetal heart rate and uterine
      contraction. METHODS: Twenty-nine pregnant women with singleton pregnancies after
      28 weeks of gestation were monitored using a portable cardiotocogram during
      driving, and the results obtained before and after driving were compared.
      RESULTS: Baseline fetal heart rate and its variability, as well as periodic fetal
      heart rate patterns, showed no abnormal patterns during car driving. Automobile
      driving in late pregnancy was not a reinforcement factor for uterine activity.
      Maternal systolic and diastolic blood pressure and heart rate showed no specific
      characteristic or adverse change during driving. CONCLUSION: The results of this
      study suggest that automobile driving in the third trimester of pregnancy has no
      adverse influences on either pregnant women or fetuses.

PMID- 14718015
TI  - Role of prophylactic oophorectomy at the time of hysterectomy in ovarian cancer
      prevention in Thailand.
AB  - AIM: To determine the impact of prophylactic oophorectomy on ovarian cancer
      prevention in Thai women by estimating the magnitude of reduction in ovarian
      cancer incidence in Thailand if the procedure was routinely offered. METHODS: A
      database of 752 women with epithelial ovarian cancer treated at Chiang Mai
      University Hospital between January 1990 and December 2001 was reviewed in an
      attempt to identify those who had hysterectomy performed for indications other
      than ovarian and corpus cancer with conservation of one or both ovaries prior to
      diagnosis of ovarian cancer. Pertinent clinical and pathologic data of the women
      in this subset were further reviewed in detail. RESULTS: Of 752 ovarian cancer
      patients, 13 (1.73%) had hysterectomy performed prior to the diagnosis of ovarian
      cancer with only one woman (0.13%) having had a hysterectomy at the age of 45 or
      above. The mean interval between the hysterectomy and the diagnosis of ovarian
      cancer was 9.9 years (range 2-25 years). Considering the rate of prior
      hysterectomy at age 45 or beyond of 0.13% and the annual national ovarian cancer
      incidence of 1252 cases, an estimated one to two cases of ovarian cancer could be
      prevented annually if prophylactic bilateral oophorectomy at the time of
      hysterectomy in a woman age 45 or beyond were routinely offered in Thailand.
      CONCLUSION: Prophylactic oophorectomy at the time of hysterectomy in general Thai
      population as a preventive measure for subsequent ovarian cancer should not be
      recommended without complete knowledge of patients' socioeconomic background and
      propensity to comply with hormone replacement therapy regimens.

PMID- 14718016
TI  - Vaginal delivery in a woman with uncorrected coarctation of aorta.
AB  - Aortic coarctation is an uncommon condition complicating pregnancy and is
      associated with increased morbidity and mortality. Due to the perceived risk of
      aortic dissection/rupture during labor, the rate of cesarean delivery is higher
      in these women. We report a young woman with uncorrected coarctation of aorta who
      had two successive vaginal deliveries with successful maternal and neonatal
      outcome. Cesarean delivery is not mandatory for women with coarctation of aorta.

PMID- 14718017
TI  - Prospective study of saline infusion sonohysterography in evaluation of
      perimenopausal and postmenopausal women with abnormal uterine bleeding.
AB  - AIM: To evaluate saline infusion sonohysterography as an investigative modality
      in abnormal uterine bleeding in perimenopausal and postmenopausal women. METHODS:
      Fifty-eight patients, 52 perimenopausal and six postmenopausal women, with
      abnormal uterine bleeding were selected from the department of Obstetrics and
      Gynecology of Shrimati Sucheta Kriplani Hospital. After complete work-ups,
      transvaginal examinations were performed followed by sonohysterographies. The
      sensitivity, specificity, positive predictive values and negative predictive
      values were calculated for transvaginal sonography (TVS) and saline infusion
      sonohysterography as compared with findings of hysteroscopy/hysterectomy.
      RESULTS: Saline infusion sonohysterography was performed in 56 cases. It could
      not be done in one perimenopausal and one postmenopausal woman. Cavity was normal
      in 41 perimenopausal and five postmenopausal women. Ten women displayed
      abnormalities. Two had submucosal fibroids, two had intramural fibroids, one had
      fibroid polyp, three had endometrial polyps and two patients had endometrial
      growths. We found that TVS missed three endometrial polyps and one endometrial
      growth and led to mislabeling two intramural fibroids as submucosal. On comparing
      the sonohysterographic findings with those of hysteroscopy or hysterectomy, one
      endometrial polyp and one endocervical polyp was missed on sonohysterography, and
      one false positive growth was observed on sonohysterography. The sensitivity,
      specificity, positive predictive value and the negative predictive value of TVS
      were 84.8%, 79%, 82.4% and 82%, respectively. The sensitivity, specificity,
      positive predictive value and the negative predictive value of saline infusion
      sonohysterography were 94.1%, 88.5%, 91.4% and 92%, respectively. CONCLUSION:
      Saline infusion sonohysterography is a safe, convenient, time conserving, cost
      effective, easily accessible and acceptable investigative modality. It definitely
      enhances the diagnostic potential of TVS in assessment of endometrium and
      intracavitary pathologies.

PMID- 14718018
TI  - Uterine rupture of cesarean scar related to spontaneous abortion in the first
      trimester.
AB  - We report the case of a 31-year-old Japanese female diagnosed by transvaginal
      ultrasonography to have a spontaneous uterine rupture in the first trimester. Her
      condition was complicated by diabetes mellitus type 1. Her previous pregnancy had
      resulted in an emergency cesarean section by transverse incision of the lower
      uterine segment with single-layer suture at 37(+4) weeks of gestation.
      Transvaginal ultrasonography displayed both a gestational sac located in the
      anterior lower uterine segment and a defect in the uterine wall located at the
      site of the previous cesarean delivery scar. Pelvic magnetic resonance imaging
      showed that the uterine muscle layer was discontinuous and the gestational sac
      was almost outside the uterine cavity, accompanied by mild hemorrhaging within
      the endometrial cavity. The defect in the lower uterine wall was round in shape
      and was 3 cm in diameter. Since uterine ruptures can occur during all gestational
      periods, it is important to pay attention to the uterine wall where any cesarean
      incision was previously made.

PMID- 14718019
TI  - Schonlein-Henoch purpura during pregnancy: Case report and review of the
      literature.
AB  - The clinical features of Schonlein-Henoch Purpura (SHP) consist of non
      thrombocytopenic purpura in association with joint, gastrointestinal and renal
      involvements. Because it is uncommon in adults, there is little information on
      the effects of SHP on pregnancy in the literature. This report documents the
      clinical findings and outcome of an uncommon case of SHP affecting a woman who
      was 25 weeks pregnant. Prompt steroid-therapy induced a rapidly favorable course
      and successful vaginal delivery at 40 weeks gestation. If SHP develops during
      pregnancy, it is not always easy to distinguish from obstetrical complications
      such as pre-eclampsia. An early diagnosis is important especially if renal
      involvement exists, because the prognosis for this disease can include
      nephropathy and it therefore needs close monitoring.

PMID- 14718020
TI  - Evaluation of depressive conditions among Japanese patients at a menopause
      clinic.
AB  - AIM: To examine current depressive tendencies among Japanese patients visiting a
      menopause clinic with complaints of climacteric symptoms. METHODS: The subjects
      were 389 Japanese women (age range: 45-60 years; mean: 51.4 +/- 3.8 years) who
      visited the menopause clinic in Department of Obstetrics and Gynecology, Keio
      university hospital, reporting climacteric symptoms. Their depressive tendencies
      were examined with the SDS (Self-rating Depression Scale, filled out by the
      patient). RESULTS: The SDS was computed to be 42.4 +/- 9.9. Ninety-three (23.9%)
      suffered from an intermediate or higher level depressive tendency; 132 (33.9%)
      had a mild depression; and 164 (42.2%) were free of any depressive tendency. It
      was concluded that more than one-half of the subjects suffered from some form of
      depression. Correlations between age, time after menopause/oophorectomy, and
      depressive tendency were ambiguous. In comparing the total scores of SDS for pre
      , peri-, and postmenopause groups, the incidence of probable depression was
      higher in the second group, but no significant differences were noted among each
      group. When the parameters were compared in relation to their hormonal
      environments, the natural menopause group rated significantly higher in the
      scores related to sleep disturbance, hopelessness and dissatisfaction than the
      premenopause group. The number of those who probably exhibited mild or more
      exaggerated depression was significantly lower in the surgical menopause group in
      comparison with the natural menopause group. CONCLUSION: A depressive tendency
      occurred frequently among Japanese patients with menopausal disorders. It is
      important to evaluate the mental status of these patients with the aid of an
      appropriate tool.

PMID- 14718021
TI  - Investigation of the incidence of hepatitis E virus among pregnant women in
      Turkey.
AB  - AIM: The aim of our study was to determine the prevalence of hepatitis E virus
      (HEV) among pregnant and non-pregnant women in Middle Anatolia, identify the
      factors that affect being HEV positive and to study the effects of HEV positivity
      on mother and fetus. METHODS: The study included 245 pregnant women who applied
      to various health centers and 76 cases in the same age range as the control.
      Blood samples taken from the cases were tested in terms of anti-HEV, IgM and IgG
      using the microELISA method. RESULTS: None of the blood samples tested revealed
      anti-HEV IgM positive, an indicator of acute infection, while 31 pregnant women
      (12.6%) and nine cases in the control group (11.8%) were found to have anti-HEV
      IgG positive (P > 0.05). It was seen that in pregnant women such factors as
      advanced age, lower educational and income levels and rural residence were
      correlated with higher anti-HEV IgG positive values (P < 0.05). HEV infection is
      endemic in Afyon and its vicinity. There were no statistical differences between
      pregnant women and non-pregnant women at similar ages in terms of HEV
      seropositivity. CONCLUSION: It can be suggested that pregnancy does not
      constitute a predisposition to HEV infection.

PMID- 14718022
TI  - Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL
      and BENE, in cervical squamous cell cancers.
AB  - Persistent human papillomavirus infections cause infected epithelial cells to
      lose cellular polarity leading to cell transformation. Glycolipid-enriched
      membrane (GEM) rafts are implicated in polarized sorting of apical membrane
      proteins in epithelial cells and even in signal transduction. The MAL and BENE
      are essential component of the GEM raft's machinery for apical sorting of
      membrane proteins. In this study we demonstrated down-regulation of MAL and BENE
      mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of
      20 cases, for MAL and BENE, respectively) when compared to corresponding non
      cancerous uterine squamous cells. Allelic loss or hyper-methylation was not
      accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers
      in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of
      the MAL and BENE genomic region. In addition, we note down-regulation of these
      genes in established cervical cancer cell lines. These results suggest that down
      regulation of MAL and BENE genes, which are essential components of the cellular
      polarized sorting system, play an important role in human cervical squamous cell
      cancer development.

PMID- 14718023
TI  - Serum carbohydrate antigen elevations in endometrial adenocarcinomas:
      characterization of DU-PAN-2 expression as a tumor marker.
AB  - AIM: To characterize serum elevations of carbohydrate antigens; DU-PAN-2, CA19-9,
      sialyl Lewisx and CA125 in endometrial adenocarcinomas (EMACs), particularly
      focusing on the clarification of DU-PAN-2 expression profiles. METHODS: Sixty
      four resected EMACs of endometrioid type were used. The preoperative serum values
      of four markers were measured and comparatively analyzed regarding the
      relationship between histological grade and clinicopathological stage. RESULTS:
      The overall ratios of positive cases were 26.2% for DU-PAN-2, 25.0% for CA19-9,
      13.6% for sialyl Lewisx, and 35.5% for CA125. DU-PAN-2 decreased as the grading
      went up (G1: 410.3 +/- 243.8 to G3: 246.7 +/- 90.0 U/mL), however, the reverse
      was true with CA19-9 (G1: 123.9 +/- 147.4 to G3: 320.0 +/- 180.0 U/mL). Sialyl
      Lewisx showed a strong tendency towards high elevation in G1 (346.3 +/- 102.6
      U/mL), compared to G3 (< 2.5 U/mL). CA125 increased markedly as the grading went
      up (G1: 43.5 +/- 6.3 to G3: 578.0 +/- 10.0 U/mL). During staging-up from I + II
      to III + IV, the positive ratios inclined in all four markers as follows: DU-PAN
      2, 18.4-53.3%; CA19-9, 20.4-40.0%; sialyl Lewisx, 11.4-22.2%; CA125, 31.8-44.4%.
      Serum elevations and positive ratios were correlated for DU-PAN-2, CA19-9 and
      CA125, while the reverse relationship was found for sialyl Lewisx. CONCLUSION: It
      is suggested that DU-PAN-2 tends to be produced more in well-differentiated
      components of EMACs than in poorly differentiated ones. Since approximately half
      the cases with EMAC were serologically positive for DU-PAN-2 in stage III + IV,
      the marker is believed to be of much use for monitoring the cases with an
      extrauterine extent.

PMID- 14718024
TI  - Changes of lipocalin-type prostaglandin D synthase level during pregnancy.
AB  - AIM: Prostaglandin D (PGD), synthesized by lipocalin-type prostaglandin D
      synthase (L-PGDS), has marked effects on a number of biological processes,
      including the prevention of platelet aggregation and the relaxation of vascular
      smooth muscle. The aim of the study presented here was to examine the
      significance of L-PGDS in human pregnancy. METHODS: We measured the concentration
      of plasma L-PGDS in pregnant and non-pregnant women, and the concentration of L
      PGDS in the umbilical cord blood, amniotic fluid and urine of newborns by enzyme
      linked immunoabsorbent assay. To determine the localization of L-PGDS, we
      performed immunohistochemical analysis. To evaluate the usefulness of diagnosis
      of rupture of membranes (ROM), we determined the concentration of L-PGDS in
      cervicovaginal secretions. RESULTS: Pregnant women and non-pregnant women had
      similar L-PGDS concentrations (0.57 +/- 0.13 microg/mL vs 0.53 +/- 0.07
      microg/mL). Umbilical cord blood, amniotic fluid and newborn urine contained
      higher L-PGDS concentrations (1.87 +/- 0.73 microg/mL, 2.62 +/- 0.86 microg/mL,
      6.31 +/- 4.62 microg/mL, respectively) than maternal blood. The concentration of
      L-PGDS in amniotic fluid from 19 weeks onward was significantly greater than that
      at 15-18 weeks (3.201 +/- 0.384 microg/mL, n = 6 vs 1.735 +/- 0.477 microg/mL, n
      = 4; P < 0.05). Immunohistochemistry revealed that the amniotic cells of the
      placenta expressed L-PGDS. The sources of L-PGDS in amniotic fluid are fetus
      urine and amniotic cells. The concentration of L-PGDS in cervicovaginal
      secretions with rupture of membrane (ROM) were significantly higher than those
      without ROM. CONCLUSION: The measurement of L-PGDS in cervicovaginal fluid was
      useful in the detection of ROM during pregnancy.

PMID- 14718025
TI  - Fit to practise?

PMID- 14718026
TI  - Investigation into the nutritional status, dietary intake and smoking habits of
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND AIMS: Weight loss and reduced fat-free mass are prevalent amongst
      patients with chronic obstructive pulmonary disease (COPD). However, the causes
      of this weight loss are not clear. The aims of this study are to investigate the
      factors affecting body weight and dietary intake in a group of outpatients with
      COPD, and to investigate any differences between adequately nourished and
      malnourished patients. METHODS: In 103 stable outpatients, nutritional status was
      assessed using Body Mass Index (BMI) and upper arm anthropometry. Lung function,
      smoking status, exercise tolerance, dietary intake, dietary problems and health
      related quality of life were assessed. Patients were classed as either adequately
      nourished or malnourished. RESULTS: Twenty-three per cent of subjects were
      classed as malnourished. The malnourished subjects had lower lung function
      measurements, suffered more dietary problems and had lower nutritional intake
      compared with the adequately nourished subjects. They also had poorer fatigue
      scores. In linear regression analysis, the factors that had the most effect on
      BMI were a low transfer factor, presence of early satiety, and being a current
      smoker. CONCLUSION: Important differences were found between adequately nourished
      and malnourished subjects. These differences move us closer to understanding how
      best to screen and treat this group of patients.

PMID- 14718028
TI  - The testing of clinical skills in dietetic students prior to entering clinical
      placement.
AB  - BACKGROUND: One of the most important requirements for contemporary education of
      a health care professional is to develop a framework for theory and practise
      which results in attainment of professional competencies suitably robust for a
      lifetime of practise (Howe, 2002). In the context of those educating
      preregistration dietitians, this offers the challenge of presenting the student
      with innovative curricula designed to deliver the appropriate level of knowledge
      and understanding together with emphasis on skill and attitude development. The
      purpose of this study was to allow preregistration students the opportunity to
      practise key clinical skills prior to clinical placement and test skills
      acquisition using the model of an objective structured clinical examination
      (OSCE). METHODS: The learning experience of the student was altered to
      accommodate a more conceptually-driven, problem-centred, case-based approach. The
      curriculum was adjusted to incorporate a short clinical skills programme where
      emphasis was deliberately placed on skill acquisition. At the conclusion of this
      clinical skills programme, and prior to the students entering clinical placement,
      skill performance by students was tested using the OSCE. The method of testing
      was also evaluated by students. RESULTS: The OSCE was delivered to 37 preclinical
      students. Four of the test candidates (11%) failed in at least one of the skill
      areas: these students performed similarly during clinical placement. Twenty-one
      (57%) students returned the post-OSCE questionnaire. Twenty (95%) students
      reported a positive experience; 20 (95%) students reported initial anxiety that
      diminished as the test progressed. CONCLUSION: The Project Team was confident
      with the novel approach taken in re-designing the curriculum: to include a
      dedicated clinical skills programme, together with addition of the testing of
      clinical skills using the OSCE model. These curriculum changes were deemed to be
      highly appropriate additions to the student experience in determination of skill
      performance of students prior to clinical placement.

PMID- 14718029
TI  - Monitoring the development of clinical skills during training in a clinical
      placement.
AB  - BACKGROUND: The education and training of health care practitioners has undergone
      recent reform, and indicate that curricula should place emphasis on the
      development of clinical skills and attitude. The purpose of this study was two
      fold: to define the key skills necessary for a competent dietetic student
      practitioner and to devise a reliable assessment tool to measure and track
      performance in these key skill areas throughout the period of clinical placement.
      METHODS: Key clinical skills were identified by a concensus group of experienced
      dietitians and academic practitioners. An assessment tool was then developed to
      measure these attributes in 43 students undertaking clinical placement at a
      number of training centres in Scotland. Development of skills was tracked for the
      entire duration of placements using the novel assessment tool. The assessment
      tool used a visual analogue scale (VAS) as the measuring score. RESULTS: A high
      level of skill attainment was equated with high VAS scores. Performance in three
      of the four key skills (written skills: r = 0.762, P </= 0.001; interviewing
      skills: r = 0.697, P < 0.001; and dietary assessment technique: r = 0.697, P </=
      0.001) showed impressive correlation co-efficients, indicating a striking and
      significant positive correlation with the length of training. A high skill
      performance level attainment was achieved by week 16/17 of training. CONCLUSION:
      The authors are confident that the assessment tool is valid and reliable and
      measures skill performance objectively. A high level of skill attainment was
      observed in most students by about the mid-point in training: this allows the
      student to consolidate these skills in the latter stages of training which is in
      keeping with educational and practice philosophy of placement learning outcomes.

PMID- 14718030
TI  - The development and evaluation of Student Training, Education and Practice for
      Dietetics CD-ROM: a computer-assisted instruction programme for dietetic
      students.
AB  - The Student Training, Education and Practice for Dietetics (STEP-DIET) CD-ROM was
      developed at the University of Surrey to prepare dietetic students for the
      practical dietetic training component of their Nutrition/Dietetics degree. This
      study aimed to evaluate student response to the programme and its effectiveness
      as a teaching tool, based on the evaluation framework of D.L. Kirkpatrick
      (Evaluating a Course, 2nd edn. London, Kogan Page). Quantitative and qualitative
      methodologies were employed, with 41 dietetic students, separated by year group,
      completing questionnaires and taking part in six focus groups, at the University
      of Surrey. Student attitudes towards the instruction method and the STEP-DIET
      programme itself were investigated, in conjunction with their perceived learning
      achievements. Students rated the programme highly in terms of design and content,
      however, there was a reluctance to accept computer-assisted instruction (CAI) as
      a sole teaching method. A number of learning achievements relevant to dietetic
      practice were reported including a perceived increase in ability to conduct a
      dietetic interview and an increased understanding of the management of Type 2
      diabetes. In general students reacted positively to the STEP-DIET programme and
      it was perceived by students to be effective in preparing them for the practical
      component of their dietetic training.

PMID- 14718031
TI  - Impact of tea drinking on iron status in the UK: a review.
AB  - BACKGROUND: The aims of this review are (1) to evaluate the literature on the
      likely impact of tea drinking on the iron status of different groups within the
      UK population and (2) to formulate targeted and evidence based advice on tea
      drinking in the context of iron nutrition in different groups of people. METHOD:
      A literature search identified 35 references specific to the effects of black tea
      on iron absorption and iron nutrition plus one recent review article. Each study
      was assessed in terms of methodogical quality and relevance to the tea drinking
      patterns of the UK population. RESULTS: There is clear evidence to show that tea
      drinking limits the absorption of nonhaem iron. However, there are few studies
      which have assessed the influence of tea drinking on indicators of iron status.
      There are no intervention studies and the conclusions reported in this review are
      based on 12 observational studies mostly from other countries. These studies have
      reported either significant negative correlations between tea drinking and blood
      indicators of iron status or more cases of anemia in tea drinkers compared with
      nontea drinkers. Many of the studies reviewed report additional relationships
      between iron status indices and other factors (both dietary and nondietary),
      highlighting the complexity of influences on iron absorption and iron status.
      CONCLUSION: From the available evidence there is no need to advise any
      restriction on tea drinking in healthy people with no risk of iron deficiency. In
      groups at risk of iron deficiency the advice should be to drink tea between meals
      and to wait at least 1 h after eating before drinking tea.

PMID- 14718032
TI  - The opinion of Dutch dietitians about functional foods.
AB  - OBJECTIVE: To obtain information about Dutch dietitian's attitudes, perceived
      knowledge, training preferences, counselling procedures, opinions about post
      launch monitoring, and personal consumption of functional foods. DESIGN: A self
      administered, 62-item, postal survey in 2002. SUBJECTS: Five hundred randomly
      selected registered dietitians. The response rate was 49% (n = 238). RESULTS: The
      responders (mean age +/- SD: 40 +/- 9 years) had regular contact with clients
      (90%), and many (71% of 90%) advised about functional food use. Sixty-nine per
      cent hardly consumed any functional food themselves. Eighty-seven per cent of the
      responders would greatly appreciate courses given by scientists. Confusion
      existed about usage practices, target groups, safety, efficacy, and claims:
      between 42 and 89% agreed with the statements about uncertainties. Nonetheless,
      69% felt that functional foods could theoretically contribute to good bodily
      functioning. Ninety per cent thought post-launch monitoring (PLM) important, but
      ideas about a common dietetic contribution to PLM did not emerge. CONCLUSIONS:
      Although functional foods potentially contribute to a healthful diet, there is
      still confusion among dietitians about claims, safety, efficacy and product
      handling aspects. It is time to meet dietitians' repeated requests to provide
      education by noncommercial experts. In the meantime, dietitians themselves should
      have more say in the PLM debate because they should and could play an important
      role.

PMID- 14718033
TI  - A survey to assess physical activity promotion by Registered Dietitians.
AB  - BACKGROUND: Convincing evidence has emerged in recent years for the role of
      physical activity (PA) in the prevention and treatment of many chronic diseases.
      These include both physical and mental health problems, which are likely to be
      encountered by practicing dietitians. This study aimed to identify whether NHS
      based Registered Dietitians (RDs) currently promote PA to their patients and if
      so, how they do it and with which patients. METHOD: An anonymous questionnaire
      sent to 516 RDs in NHS teaching hospitals achieved a 77% (n = 397) return rate.
      RESULTS: Ninety-three per cent of respondents reported regularly promoting PA
      particularly with new patients. Among active PA promoters, 87% reported
      encouraged daily accumulation of PA, 50% focused on sport and exercise and 52%
      referred patients to GPs or Physiotherapists for advice. Distinctive levels and
      styles of PA promotion were found to be related to levels of recent training in
      the field although fewer than one in four had actually received any formal
      training. CONCLUSIONS: A high interest in further PA-specific training (95% of
      all respondents), together with high variability in the type and quality of
      advice suggests the need to develop further in-service training specifically for
      RDs.

PMID- 14718034
TI  - Beware the fatty acid-free sausage!

PMID- 14718039
TI  - Cystic fibrosis mutation screening before assisted reproduction.
AB  - Cystic fibrosis (CF) is the most common autosomal recessive disease in
      Caucasians, with a reported incidence of one in 2500. In 97-98% of men with CF, a
      congenital bilateral absence of the vas deferens (CBAVD) blocks the transport of
      spermatozoa from testicular or epididymal structures to the outer genital tract,
      resulting in azoospermia. Abnormalities in semen parameters have also been
      identified in males with CF. Around 10% of obstructive azoospermia is congenital
      and is due to mutations the CF gene. It is therefore suggested that men who have
      CBAVD should be considered for CF screening prior to intracytoplasmic sperm
      injection (ICSI) treatment. Men with azoospermia of unknown origin should also be
      considered for screening. Couples requesting surgical sperm retrieval/ICSI should
      therefore be advised and counselled to bear an elevated risk for CF in their
      offspring. Counselling of these couples is vitally important in order to help
      them understand and cope with the diagnosis.

PMID- 14718040
TI  - Semen quality and sedentary work position.
AB  - Increased scrotal temperature can, in experimental settings, markedly disturb the
      production of semen. Sedentary work position may increase the temperature of the
      scrotum, but previous studies have failed to determine whether changes in scrotal
      temperature caused by sedentary work actually do affect semen quality. This study
      was carried out to elucidate the possible harmful effects of sedentary work on
      sperm count and other semen characteristics. In 1981-1983 a semen sample was
      obtained from 3119 men who attended an infertility workup in one of four Danish
      fertility centres. A total of 2517 men returned a postal questionnaire with
      information on life style, leisure time activities, occupational history and job
      duties. Information on job specific work position was obtained from The Danish
      Work Environment Cohort study 1990 (DWECS). In this analysis DWECS data for a
      total of 1747 men was included from men aged 18-39 years with >30 h of work per
      week. For all job titles represented in the DWECS, the mean proportion of
      sedentary work was estimated. The sperm cell concentration was 30.6 million/mL
      among men in the quintile with lowest job specific sedentary work compared with
      40.5 million/mL in the highest quintile. The difference was, however, not
      statistically significant. Stratification on infertility period, educational
      level of the man, fertility centre, and fertility-related disease of the spouse
      did not influence the results. The analyses do not suggest that sedentary work is
      a risk factor for abnormal semen characteristics.

PMID- 14718041
TI  - Effects of steroids on oxytocin secretion by the human prostate in vitro.
AB  - Oxytocin (OT) concentrations are elevated in prostate tissue of patients with
      benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5
      alpha-reductase activity and contractility in the prostate. In the rat prostatic
      OT concentrations are regulated by gonadal steroids, with androgens reducing but
      oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in
      man is not understood. This study investigates the effects of gonadal steroids on
      oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of
      prostate tissue from patients with BPH were incubated in Dulbecco's modified
      Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L
      dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti-androgen
      cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT.
      The amount of oxytocin secreted into the media after 3 days was measured by
      radioimmunoassay. Testosterone and DHT significantly increased oxytocin
      concentrations secreted into the media from 0.86 +/- 0.11 ng/g of tissue
      (control) to 1.51 +/- 0.14 ng/g (p < 0.01) and 1.54 +/- 0.13 ng/g (p < 0.05),
      respectively. Incubation of tissue samples with CPA resulted in oxytocin
      concentrations similar to control levels. Treatment with DES caused a significant
      increase from 1.99 +/- 0.71 to 3.98 +/- 1.36 ng/g (p < 0.05). A similar increase
      was measured in media of tissue incubated in DES plus DHT (p < 0.001). The
      results demonstrate that, unlike the rat where androgens decrease oxytocin, in
      hyperplastic human prostate tissue both androgens and oestrogens increase
      oxytocin. This imbalance in the regulation of oxytocin may result in promoting
      prostatic overgrowth in the pathogenesis of BPH.

PMID- 14718042
TI  - Phosphatidylinositol 3-kinase inhibition enhances human sperm motility and sperm
      zona pellucida binding.
AB  - Various signalling pathways are involved in the regulation of sperm motility,
      capacitation, acrosome reaction and sperm-zona binding. Recent data pointed out
      an important role for phosphatidylinositol 3-kinase (PI3K) in human sperm
      motility. However, no study as of yet has been carried out to determine the
      effect of sperm treatment with the PI3K inhibitor LY294002 on other sperm
      parameters. In the present study, we investigated the role of PI3K on human sperm
      motility, acrosome reaction and sperm-oocyte binding by using this inhibitor. We
      demonstrate that in vitro incubation of washed unselected spermatozoa with
      LY294002 increased the percentage motility and progressive motility in
      asthenozoospermia patients as evaluated by computer-aided sperm analysis. The
      compound furthermore did not influence the acrosome reaction, whilst it (further)
      slightly enhanced sperm-oocyte binding. Our results therefore imply that PI3K
      negatively affects sperm motility and oocyte binding and might suggest a possible
      therapeutic role for PI3K inhibitors in the treatment regime for
      asthenozoospermia.

PMID- 14718043
TI  - Prostasomes as zinc ligands in human seminal plasma.
AB  - Prostasomes are small vesicles, containing zinc, secreted by prostate in human
      seminal plasma and showing a physiological role on sperm properties. In this
      study, the possible correspondence between prostasomes and a prostatic high
      molecular weight protein complex, recently indicated as zinc ligand, has been
      investigated. Isolated prostasomes, examined by scanning electron microscopy,
      were dialysed to evaluate their zinc binding capacity. Furthermore, seminal
      plasma Sephadex G-75 elution was carried out before and after prostasome removal.
      Prostasome preparations, containing typical vesicles of 50-500 nm, showed a
      positive correlation between their zinc and protein levels. They were able to
      take up zinc against gradient. Furthermore, the seminal zinc amount, bound to the
      high molecular weight proteins, was strongly reduced in the free-prostasome
      sample with respect to the total seminal plasma. This study suggested the
      correspondence between the prostasomes and a high-sized zinc ligand complex of
      prostatic origin. Therefore, it demonstrated, for the first time, the zinc
      binding capacity of prostasomes, a new property which could be related to their
      biological functions.

PMID- 14718044
TI  - Serial follow-up study of serum testosterone and antisperm antibodies in patients
      with non-obstructive azoospermia after conventional or microdissection testicular
      sperm extraction.
AB  - Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection
      is becoming a first-line treatment even for non-obstructive azoospermia. The
      current focus of TESE is the identification of seminiferous tubules that contain
      spermatozoa and minimization of testicular damage. Although microdissection TESE
      has been introduced as a preferred procedure for sperm retrieval, no serial
      follow-up studies of testicular damage have been reported. In the present study,
      we assayed serum testosterone concentrations and for the presence of antisperm
      antibodies (ASA) for 1 year after conventional multiple TESE or microdissection
      TESE and compared postoperative testicular damage between procedures. Thirteen
      patients who underwent conventional multiple TESE and 12 patients who underwent
      microdissection TESE were included in this study. Serum total and free
      testosterone concentrations were evaluated before operation and 1, 6 and 12
      months after TESE. Serum ASA was also evaluated before and 12 months after TESE.
      Serum total and free testosterone concentrations in all patients in both groups
      showed no significant postoperative decrease. A comparison between the two groups
      of serum total and free testosterone concentrations showed no significant
      difference (total testosterone, p = 0.2477; free testosterone, p = 0.3098). No
      incidence of new ASA formation was identified in the present study. In
      conclusion, TESE procedures cause neither a decrease of serum testosterone nor
      formation of ASA. Serum testosterone concentration are similar between patients
      in the conventional multiple TESE and microdissection groups. Therefore,
      microdissection TESE is safe with respect to testicular damage, particularly for
      patients with hypogonadism.

PMID- 14718045
TI  - Susceptibility gene for non-obstructive azoospermia in the HLA class II region:
      correlations with Y chromosome microdeletion and spermatogenesis.
AB  - We previously reported an association between the human leukocyte antigen (HLA)
      haplotype DRB1*1302-DQB1*0604 in the HLA class II region and non-obstructive
      azoospermia in Japanese men. To identify possible associations between the HLA
      DRB1*1302-DQB1*0604 allele in the HLA class II region and azoospermia factor
      (AZF) deletion in the Y chromosome, we performed genomic polymerase chain
      reaction (PCR) analysis of the AZF region. We then determined spermatogenic
      impairment (Johnsen score) in testicular biopsy specimens from patients with or
      without the DRB1*1302-DQB1*0604 haplotype. The AZF microdeletion rate in patients
      with this haplotype was 3.85%, compared with 11.8% in others (no correlation).
      However, Johnsen scores in patients with the DRB1*1302-DQB1*0604 haplotype were
      3.13 +/- 1.34 (mean +/- SD), compared with 3.70 +/- 1.51 in others (p < 0.05).
      While the DRB1*1302-DQB1*0604 haplotype acts independently from Y chromosome
      deletion, the haplotype might either act directly, or be functionally related to
      an unknown autosomal gene. In either case, this haplotype showed association with
      severe spermatogenic impairment.

PMID- 14718046
TI  - Expression of cavernous transforming growth factor-beta1 and its type II receptor
      in patients with erectile dysfunction.
AB  - It has been hypothesized that transforming growth factor-beta1 (TGF-beta1)
      signalling is involved in erectile dysfunction (ED). This study was undertaken to
      elucidate in detail whether expression of TGF-beta1 and its type II receptor is
      clinically related to various causes of ED. Fifty-four patients with ED and 24
      potent men were the subjects of this study. After multidisciplinary work-up, the
      ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n
      = 33). In every subject, percutaneous cavernous biopsy was performed using a
      Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres
      and immunohistochemical staining to evaluate both TGF-beta1 and its type II
      receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen
      fibres were significantly more abundant in men with vasculogenic ED (72.7 +/-
      17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0
      +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1
      was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control
      subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II
      receptor expression was also significantly increased in vasculogenic ED (3.9 +/-
      1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or
      neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the
      hyperlipidaemia and the atherosclerosis patients showed significantly more
      fibrosis than those without the condition (p < 0.05). The abundance of collagen
      fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001)
      and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that
      TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED
      in man. Patients with vascular risk factors such as hyperlipidaemia and
      atherosclerosis are liable to ED by activation of this pathway.

PMID- 14718047
TI  - Androgen-dependent blood flow control and morphological changes of the
      capillaries in rat prostate.
AB  - To clarify the effect of androgens on the microcirculation of the prostate, organ
      blood flow and ultrastructural features of the capillaries were investigated. In
      the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured
      using a laser Doppler flowmetry, and the morphological features of the
      subepithelial capillaries were investigated and their luminal area was measured
      using transmission electron microscopy and a computed image analyzer at 1, 2, 3,
      and 7 days after castration, and 2 days after castration and gradational
      testosterone supplementation. The capillaries of the VP were classified into
      three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3).
      Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the
      luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2
      days after castration. These reductions of the blood flow and the luminal area
      were gradationally prevented by testosterone supplementation. In the
      morphological features of the capillary, type 1 had rapidly shifted to types 2
      and 3 after castration, and the shift of the capillary type was significantly
      prevented by the testosterone supplementation. These results clearly demonstrated
      that the androgen-dependent ultrastructural and morphological features in
      subepithelial capillaries revealed local microcirculatory conditions correlating
      the organ blood flow changes in VP.

PMID- 14718048
TI  - Spectrophotometric application of resazurin reduction assay to evaluate boar
      semen quality.
AB  - The resazurin reduction assay depends on the ability of metabolically active
      cells to reduce the resazurin redox dye to resorufin. In the present study we
      applied and made a diagnostic evaluation of a spectrophotometric application of
      the resazurin reduction assay to assess the colour change of resazurin reduction
      in butanol extracted colour to evaluate boar semen quality. Forty-one samples of
      boar semen from various breeds were included in the study. The absorption peaks
      for resazurin and resorufin were found to be 610 and 575 nm, respectively.
      Absorbance at 610 nm, where the minimum overlap of the two peaks was observed,
      was used in further analysis. Spearman rank correlation analysis was used to
      determine the correlation between the resazurin reduction assay and various semen
      parameters. The highest correlations were observed with the concentration of
      motile spermatozoa (r = -0.841; p < 0.001), sperm concentration (r = -0.833; p <
      0.001), sperm index (-0.826; p < 0.001) and concentration of viable spermatozoa
      (r = -0.763; p < 0.001). Sensitivity and specificity, at 94.1 and 91.7%,
      respectively, indicate that the present test is highly accurate in discriminating
      between the samples according to the sperm index. When motile sperm concentration
      was used to distinguish between good and poor samples, high sensitivity (93.6%)
      was also found, whereas the test was only moderately, 80%, specific. The
      stability of butanol extracts in terms of A610 at different times of measurement
      confirmed that the resazurin reduction could be spectrophotometrically measured
      within 7 days from the time of assay performance, making the assay much more
      useful. Based on these results, the assay could be used as an additional tool for
      evaluating the quality of boar semen.

PMID- 14718050
TI  - CONSORT guidelines applied to an exemplar paper.

PMID- 14718051
TI  - Expression of transforming growth factor-beta 1 (TGF-beta 1) in odontogenic
      cysts.
AB  - AIM: To evaluate the positivity to transforming growth factor-beta 1 (TGF-beta 1)
      in different types of odontogenic cysts. METHODOLOGY: A total of 30 radicular
      cysts (RCs), 27 follicular cysts (FCs) and 28 odontogenic keratocysts (OKCs) were
      evaluated for immunohistochemical analysis of TGF-beta 1. TGF-beta 1 was
      evaluated in blood vessels, stromal cells (fibroblasts) and pluristratified
      squamous epithelium. TGF-beta 1 expression was determined by evaluating the
      number of positive elements. TGF-beta 1 expression was determined by evaluating
      1000 cells in the pluristratified squamous epithelium (500 in the basal and
      parabasal layers, and 500 in the superficial layer) and 500 cells (the
      fibroblasts in the stroma) for each specimen, and counting the number of positive
      cells. The number of positive vessels was evaluated in 10 high power fields
      (HPF). The Chi-square test was used to evaluate differences between the two
      groups (RC + FC and OKC). A P-value <0.05 was considered to indicate statistical
      significance. RESULTS: A higher and statistically significant positivity was
      found in the basal-suprabasal epithelial layers (P=0.0011), superficial
      epithelium (P=0.053) and stromal cells (P=0.0002) of orthokeratotic and
      parakeratotic OKC as compared with RC and FC. CONCLUSIONS: These differences
      suggest that control of the cell cycle may be abnormal in orthokeratotic OKCs.
      These OKCs may have an intrinsic growth potential not present in other cyst
      types.

PMID- 14718052
TI  - Nonsurgically retreated root filled teeth--radiographic findings after 20-27
      years.
AB  - AIM: To identify periapical changes in nonsurgically retreated root-filled teeth
      20-27 years after root canal treatment. METHODOLOGY: From an original material of
      429 roots, retreated by undergraduate students in a teaching clinic, 112 roots in
      70 individuals could be evaluated radiographically 20-27 years after treatment.
      The same roots had been studied 10-17 years earlier. The periapical condition was
      registered and compared by three observers in two series of intraoral radiographs
      taken 10-17 and 20-27 years after treatment. A retrospective analysis was
      performed to gain information about probable endodontic and nonendodontic reasons
      for extractions of lost roots, by evaluating their periapical status immediately
      after retreatment and at the 10-17-year follow-up. RESULTS: Favourable outcomes
      were observed in 11 roots that had radiolucencies at the 10-17-year follow-up.
      Eight of these roots had periapical pathosis preoperatively, five of them filled
      with surplus root filling material. The percentage of cases recorded as normal
      condition at the final follow-up was 95.5%, including five cases initially
      recorded with increased width of the apical periodontal space. Delayed healing as
      a result of surplus root filling material explained most of the cases with
      favourable outcome assessed many years after treatment. Twenty-eight roots were
      lost because of extraction during the observation period, 17 during the last 10
      years. Based on status at previous follow-ups, endodontic failure seems to
      represent a minor reason for extraction in the material. CONCLUSION: Late
      periapical changes, with more successful cases, were recorded when a 10-17-year
      follow-up after root canal treatment was extended for another 10 years.
      Persistent asymptomatic periapical radiolucencies, especially those with
      overfill, should generally not be classified as failures, as many of them will
      heal after an extended observation period.

PMID- 14718053
TI  - Cleaning of rotary nickel-titanium endodontic instruments.
AB  - AIM: To develop and evaluate an effective cleaning procedure for rotary nickel
      titanium (NiTi) endodontic instruments. METHODOLOGY: New rotary instruments
      (ProFile size 25/.04) were contaminated by preparing canals of extracted teeth.
      Three factors were evaluated to develop an effective cleaning sequence: dry or
      moist storage before cleaning; mechanical removal (brushing); and chemical
      dissolution in 1% NaOCl with ultrasonication. Debris on flutes was scored after
      staining in situ with Van Gieson's solution at x45 magnification. Debris was
      classified as stained or unstained particulate debris and organic film, and rated
      as none, slight, moderate or heavy. The effectiveness of a recommended cleaning
      sequence was tested on different instrument types and in private endodontic
      practices. RESULTS: All new instruments showed metallic spurs and fine
      particulate debris on the surfaces. After contamination, brushing alone removed
      most particulate debris, but did not remove organic film. NaOCl effectively
      removed organic film. Under laboratory conditions, the sequential cleaning
      procedures (moist storage, brushing followed by immersion in 1% NaOCl and
      ultrasonic cleaning) totally removed organic debris. Dry storage before cleaning
      or autoclaving with debris present reduced cleaning effectiveness (P<0.001, one
      way ANOVA). In three private practices, the cleaning protocol substantially
      reduced biological contamination, but complete cleaning was not always achieved
      (87% clean). CONCLUSION: Complete removal of organic debris from instruments is
      feasible using a combination of mechanical removal and chemical dissolution, but
      requires meticulous attention to details.

PMID- 14718054
TI  - Prevalence of and factors affecting postpreparation pain in patients undergoing
      two-visit root canal treatment.
AB  - AIM: This longitudinal, prospective study (i) investigated the prevalence of
      postpreparation pain during root canal treatment and (ii) evaluated the influence
      of factors affecting the pain experience. METHODOLOGY: Twenty practitioners,
      comprising general dental practitioners, MSc graduates and endodontists,
      participated in this study. The patient sample (n=272) was derived from
      consecutive patients attending the practitioners' surgeries for a two-visit root
      canal treatment on a single tooth. Demographic, medical history, preoperative and
      intraoperative data as well as pain experience on days 1 and 2 after root canal
      preparation were recorded. Intensity of pain experienced was recorded on a visual
      analogue scale (VAS) of 0-5. The data were analysed using logistic regression
      models. RESULTS: The prevalence of postpreparation pain within 48 h after
      treatment was 64.7% (n=176), but less than 10% of patients experienced severe
      pain (VAS 4 or 5) on either day 1 or day 2. The presence of preoperative pain
      (OR=2.841, P<0.001), tooth type (OR=2.008, P=0.009), systemic steroid therapy for
      other medical reasons (OR=0.181, P=0.023) and preoperative swelling (OR=2.433,
      P=0.040) were the only factors to significantly influence postpreparation pain
      experience. CONCLUSIONS: The prevalence of postpreparation pain was high, and the
      important prognostic determinants were presence of preoperative pain, tooth type,
      systemic steroid therapy and preoperative swelling.

PMID- 14718055
TI  - Dissolution of pulp tissue by aqueous solution of chlorhexidine digluconate and
      chlorhexidine digluconate gel.
AB  - AIM: To evaluate the activity of various root canal irrigants on bovine pulp
      tissue. METHODOLOGY: The irrigants tested were: 0.5, 1.0 and 2.5% sodium
      hypochlorite; 2% aqueous solution of chlorhexidine digluconate; 2% chlorhexidine
      digluconate gel (Natrosol); and distilled water as control. Bovine pulp fragments
      were weighed and placed in contact with 20 mL of each tested substance in a
      centrifuge at 150 r.p.m. until total dissolution. Dissolution speed was
      calculated by dividing pulp weight by dissolution time. Statistical analysis was
      performed using the Kruskal-Wallis test. RESULTS: Distilled water and both
      solutions of chlorhexidine did not dissolve the pulp tissue within 6 h. Mean
      dissolution speeds for 0.5, 1.0 and 2.5% sodium hypochlorite solutions were 0.31,
      0.43 and 0.55 mg min(-1), respectively. The solvent ability of chlorhexidine
      solutions was similar to that of distilled water. The results for sodium
      hypochlorite solutions, chlorhexidine solutions and distilled water were
      statistically different (P>0.01). CONCLUSIONS: Both chlorhexidine preparations
      and distilled water were not able to dissolve pulp tissue. All sodium
      hypochlorite solutions were efficient in dissolving pulp tissue; the dissolution
      speed varied with the concentration of the solution.

PMID- 14718056
TI  - Determination of pH and calcium ion release provided by pure and calcium
      hydroxide-containing AHPlus.
AB  - AIM: To compare in vitro the pH and calcium ion release provided by pure and
      calcium hydroxide-containing AHPlus. METHOD: Pure and modified AHPlus, the latter
      containing 5 and 10% (w/w) calcium hydroxide added during spatulation, were used.
      The material was spatulated and stored in 10 tubes that were 1 cm long and 1.5 mm
      in diameter, and then immersed in 20 mL deionized water before the materials had
      set. Ten tubes with zinc oxide and eugenol were used as controls. Four
      millilitres of water was removed from the flasks after 24 and 48 h, and after 7,
      14 and 30 days, and pH and calcium release were measured with a pH meter and by
      atomic absorption spectrophotometry, respectively. The results obtained at each
      time point were compared statistically. RESULTS: A more alkaline pH for AHPlus
      supplemented with 5 and 10% calcium hydroxide was recorded when compared to pure
      AHPlus; there were significant differences at 14 and 30 days (P<0.05). The
      results of calcium ion release showed no significant difference between pure
      AHPlus and zinc oxide plus eugenol (P>0.05). The comparisons between the AHPlus
      containing 10% calcium hydroxide with AHPlus containing 5% calcium hydroxide,
      pure AHPlus, zinc oxide plus eugenol demonstrated significant differences
      (P<0.05) at all periods. The comparisons between AHPlus containing 5% calcium
      hydroxide with pure AHPlus and zinc oxide plus eugenol demonstrated significant
      differences (P<0.05) at all periods of evaluation. CONCLUSIONS: The addition of 5
      and 10% calcium hydroxide to AHPlus cement favoured a more alkaline pH and
      greater calcium ion release.

PMID- 14718057
TI  - Three-dimensional observation of pulp cavities in the maxillary first premolar
      tooth using micro-CT.
AB  - AIM: To observe three-dimensional morphological changes with age in the pulp
      cavities of maxillary first premolar teeth. METHODOLOGY: The specimens used in
      this study were 10 maxillary first premolar teeth (five males and five females)
      obtained from patients in three age groups, namely in their twenties (20s),
      forties (40s) and sixties (60s). Each specimen was imaged by a micro-CT to
      reconstruct the three-dimensional structure. Then, using the reconstructed
      images, the morphological characteristics of the pulp cavity, the volume ratio at
      the horn region, the floor region and the overall region of the pulp chamber and
      the diameters of the buccal and lingual orifices of the root canals were compared
      between the three age groups. RESULTS: The mesio-distal widths and the heights of
      the pulp cavity decreased with age. The volume ratio and the diameter of the root
      canal orifices also decreased. The decrease in volume was not constant but showed
      a large decrease between the 20s and the 40s, compared to those of 40s to 60s.
      CONCLUSIONS: Morphological features of the pulp cavity of maxillary first
      premolar teeth in different age groups were observed three dimensionally using
      micro-CT. Decreases in pulp cavity size and shape with age were clarified using a
      three-dimensional technique.

PMID- 14718058
TI  - Effect of nonvital bleaching with 10% carbamide peroxide on sealing ability of
      resin composite restorations.
AB  - AIM: To (i) determine the effect of nonvital bleaching with 10% carbamide
      peroxide on the sealing ability of resin composite restorations bonded with a
      self-etching adhesive system; and (ii) compare the effects of antioxidant
      treatment and delayed restoration after bleaching on marginal seal. METHODOLOGY:
      Forty-eight noncarious maxillary incisors were divided into four groups (n=12)
      after conventional root canal treatment was completed. In group 1, access
      cavities were restored with a self-etching adhesive system and resin composite.
      In the remaining three groups, 10% carbamide peroxide bleaching gel was placed
      into the access cavities for periods of 8 h per day for 1 week. They were then
      restored in the same manner as group 1. Group 2 consisted of specimens restored
      immediately after bleaching. Group 3 specimens were treated with the antioxidant,
      10% sodium ascorbate, whereas group 4 specimens were immersed in artificial
      saliva for 1 week before restoration. Ten specimens in each group were then
      subjected to dye leakage; the remaining 2 specimens were examined in a SEM
      (Jeol/JSM 5200, Tokyo, Japan). The dye penetration was assessed with the standard
      scoring system. Statistical analysis was carried out using the Kruskal-Wallis and
      the Mann-Whitney tests. RESULTS: Groups 1, 3 and 4 exhibited similar leakage
      patterns and significantly less leakage than group 2 (P<0.0083). SEM examination
      of groups 1, 3 and 4 specimens demonstrated close adaptation of resin composite
      to cavity walls, whereas group 2 specimens did not. CONCLUSION: Nonvital
      bleaching with 10% carbamide peroxide adversely affected the immediate sealing
      ability of resin composite restoration; both 10% sodium ascorbate treatment and a
      1-week delay in restoration following bleaching improved the reduced sealing
      ability of resin composite.

PMID- 14718061
TI  - Development and validation of the CAM Health Belief Questionnaire (CHBQ) and CAM
      use and attitudes amongst medical students.
AB  - BACKGROUND: The need for Complementary and Alternative Medicine (CAM) and
      holistic approaches in allopathic medical school curricula has been well
      articulated. Despite increased CAM instruction, feasible and validated
      instruments for measuring learner outcomes in this content area do not widely
      exist. In addition, baseline attitudes or beliefs of medical students towards
      CAM, and the factors that may have formed them, including use of CAM itself,
      remain unreported. METHODS: A 10-item measure (CHBQ--CAM Health Belief
      Questionnaire) was constructed and administered to three successive classes of
      medical students simultaneously with the previously validated 29-item Integrative
      Medicine Attitude Questionnaire (IMAQ). Both measures were imbedded in a baseline
      needs assessment questionnaire. Demographic and other data were collected on
      students' use of CAM modalities and their awareness and use of primary CAM
      information resources. Analysis of CHBQ items was performed and its reliability
      and criterion-related validity were established. RESULTS: Response rate was 96.5%
      (272 of 282 students studied). The shorter CHBQ compared favorably with the
      longer IMAQ in internal consistency reliability. Cronbach's coefficient alpha was
      0.75 and 0.83 for the CHBQ and IMAQ respectively. Students showed positive
      attitudes/beliefs towards CAM and high levels of self-reported CAM use. The
      majority (73.5%) of students reported using at least one CAM modality, and 54%
      reported using at least two modalities. Eighty-one percent use the internet as a
      primary source of information for CAM. CONCLUSIONS: The CHBQ is a practical,
      valid and reliable instrument for measuring medical student attitudes/beliefs and
      has potential utility for measuring the impact of CAM instruction. Medical
      students showed a high self-reported rate of CAM use and positive attitudes
      towards CAM. Short, didactic exposure to CAM instruction in the first year of
      medical school did not additionally impact these already positive attitudes.
      Unlike the IMAQ, which was intended for use with physicians, the CHBQ is generic
      in design and content and applicable to a variety of learner types. Evaluation
      measures must be appropriate for specific CAM instructional outcomes.

PMID- 14718062
TI  - The North Staffordshire Osteoarthritis Project--NorStOP: prospective, 3-year
      study of the epidemiology and management of clinical osteoarthritis in a general
      population of older adults.
AB  - BACKGROUND: The clinical syndrome of joint pain and stiffness in older people is
      the commonest cause of disability and health care consultation in this age group.
      Yet there have been few prospective studies of its course over time and its
      impact on personal and social life. We plan a cohort study in the general
      population aged 50 years and over to determine the course and prognosis of hand,
      hip, knee and foot pain, and the impact of these syndromes on participation
      levels and health care use. METHODS: All patients aged 50 years and over
      registered with 3 local general practices are to be recruited to a population
      based cohort study through the use of a two-stage mailing process. Participants
      will initially complete a "Health Survey" questionnaire. This will collect
      information on several areas of life including socio-demographics, general
      health, physical function, participation, and bodily pain. Those who state that
      they have experienced any hand problem or any pain in their hands, hips, knees,
      or feet in the previous 12 months, and also give permission to be re-contacted,
      will be mailed a "Regional Pains Survey" questionnaire which collects detailed
      information on the four selected body regions (hand, hips, knees, feet). Follow
      up data for the three-year period subsequent to cohort recruitment will be
      collected through two sources: i) general practice medical records and ii) repeat
      mailed survey.

PMID- 14718063
TI  - Neuromusculoskeletal disorders in the neck and upper extremities among drivers of
      all-terrain vehicles--a case series.
AB  - BACKGROUND: The purpose of this study was to investigate whether professional
      drivers of all-terrain vehicles (ATVs) with neck pain have a different array of
      neuromusculoskeletal disorders in the neck and upper extremities than a referent
      group with neck pain from the general population. It is hypothesized that
      exposure to shock-type vibration and unfavorable working postures in ATVs have
      the capacity to cause peripheral nervous lesions. METHODS: This study was based
      on a case series analyzed according to a case-case comparison design. The study
      population consisted of 60 male subjects, including professional drivers of
      forest machines (n = 15), snowmobiles (n = 15), snowgroomers (n = 15) and
      referents from the general population (n = 15) all of whom had reported neck pain
      in a questionnaire and underwent an extensive physical examination of the neck
      and upper extremities. Based on symptom history, symptoms and signs, and in some
      cases chemical, electroneurographical and radiological findings, subjects were
      classified as having a nociceptive or neuropathic disorder or a mix of these
      types. RESULTS: The occurrence of asymmetrical and focal neuropathies (peripheral
      nervous lesion), pure or in a mix with a nociceptive disorder was common among
      cases in the ATV driver groups (47%-79%). This contrasted with the referents that
      were less often classified as having asymmetrical and focal neuropathy (27%), but
      instead had more nociceptive disorders. The difference was most pronounced among
      drivers of snowgroomers, while drivers of forest machines were more frequently
      classified as having a nociceptive disorder originating in the muscles.
      CONCLUSION: This study found a high prevalence of assymetrical and focal
      neuropathies among drivers with pain in the neck, operating various ATVs. It
      seems as if exposure to shock-type whole-body vibration (WBV) and appurtenant
      unfavorable postures in ATVs may be associated to peripheral nervous lesions.

PMID- 14718064
TI  - Determination of iron sucrose (Venofer) or iron dextran (DexFerrum) removal by
      hemodialysis: an in-vitro study.
AB  - BACKGROUND: Intravenous iron is typically administered during the hemodialysis
      (HD) procedure. HD patients may be prescribed high-flux (HF) or high-efficiency
      (HE) dialysis membranes. The extent of iron sucrose and iron dextran removal by
      HD using HF or HE membranes and by ultrafiltration rate (UFR) is unknown.
      METHODS: Two in vitro HD systems were designed and constructed to determine the
      dialyzabiltiy of iron from a simulated blood system (SBS) containing 100 mg iron
      sucrose or iron dextran (system A) or 1000 mg iron sucrose (system B). Both in
      vitro systems utilized a 6-L closed-loop SBS system that was subject to 4
      different HD conditions conducted over 4 hours: HE membrane + 0 ml/hr UFR; HE
      membrane + 500 ml/hr UFR; HF membrane + 0 ml/hr UFR; HF membrane + 500 ml/hr UFR.
      Blood flow and dialysate flow rates were 500 ml/min and 800 ml/min, respectively.
      The dialysate compartment was a 192-L open system for system A and a 6-L closed
      loop system for system B. Samples from the SBS and dialysate compartments were
      taken at various time points and iron elimination rate and HD clearance was
      determined. Iron removal from the SBS > 15% was considered clinically
      significant. RESULTS: The greatest percentage removal from the SBS was 13.5% and 
      0.03% utilizing system A and B, respectively. Iron sucrose and iron dextran
      dialysate concentration was below the lower limits of assay (< 2 ppm) for system
      A. Dialysate recovery of iron was negligible: 0-5.4 mg system A and 5.47-23.59 mg
      for system B. Dialyzer type or UFR did not affect iron removal. CONCLUSION: HF or
      HE dialysis membranes do not remove clinically significant amounts of iron
      sucrose or dextran formulations over a 4-hour HD session. This effect remained
      constant even controlling for UFR up to 500 ml/hour. Therefore, iron sucrose and
      iron dextran are not dialyzed by HE or HF dialysis membranes irrespective of UFR.

PMID- 14718065
TI  - The single-stranded DNA-binding protein of Deinococcus radiodurans.
AB  - BACKGROUND: Deinococcus radiodurans R1 is one of the most radiation-resistant
      organisms known and is able to repair an unusually large amount of DNA damage
      without induced mutation. Single-stranded DNA-binding (SSB) protein is an
      essential protein in all organisms and is involved in DNA replication,
      recombination and repair. The published genomic sequence from Deinococcus
      radiodurans includes a putative single-stranded DNA-binding protein gene (ssb;
      DR0100) requiring a translational frameshift for synthesis of a complete SSB
      protein. The apparently tripartite gene has inspired considerable speculation in
      the literature about potentially novel frameshifting or RNA editing mechanisms.
      Immediately upstream of the ssb gene is another gene (DR0099) given an ssb-like
      annotation, but left unexplored. RESULTS: A segment of the Deinococcus
      radiodurans strain R1 genome encompassing the ssb gene has been re-sequenced, and
      two errors involving omitted guanine nucleotides have been documented. The
      corrected sequence incorporates both of the open reading frames designated DR0099
      and DR0100 into one contiguous ssb open reading frame (ORF). The corrected gene
      requires no translational frameshifts and contains two predicted
      oligonucleotide/oligosaccharide-binding (OB) folds. The protein has been purified
      and its sequence is closely related to the Thermus thermophilus and Thermus
      aquaticus SSB proteins. Like the Thermus SSB proteins, the SSBDr functions as a
      homodimer. The Deinococcus radiodurans SSB homodimer stimulates Deinococcus
      radiodurans RecA protein and Escherichia coli RecA protein-promoted DNA three
      strand exchange reactions with at least the same efficiency as the Escherichia
      coli SSB homotetramer. CONCLUSIONS: The correct Deinococcus radiodurans ssb gene
      is a contiguous open reading frame that codes for the largest bacterial SSB
      monomer identified to date. The Deinococcus radiodurans SSB protein includes two
      OB folds per monomer and functions as a homodimer. The Deinococcus radiodurans
      SSB protein efficiently stimulates Deinococcus radiodurans RecA and also
      Escherichia coli RecA protein-promoted DNA strand exchange reactions. The
      identification and purification of Deinococcus radiodurans SSB protein not only
      allows for greater understanding of the SSB protein family but provides an
      essential yet previously missing player in the current efforts to understand the
      extraordinary DNA repair capacity of Deinococcus radiodurans.

PMID- 14718066
TI  - Inter-species differences of co-expression of neighboring genes in eukaryotic
      genomes.
AB  - BACKGROUND: There is increasing evidence that gene order within the eukaryotic
      genome is not random. In yeast and worm, adjacent or neighboring genes tend to be
      co-expressed. Clustering of co-expressed genes has been found in humans, worm and
      fruit flies. However, in mice and rats, an effect of chromosomal distance (CD) on
      co-expression has not been investigated yet. Also, no cross-species comparison
      has been made so far. We analyzed the effect of CD as well as normalized distance
      (ND) using expression data in six eukaryotic species: yeast, fruit fly, worm,
      rat, mouse and human. RESULTS: We analyzed 24 sets of expression data from the
      six species. Highly co-expressed pairs were sorted into bins of equal sized
      intervals of CD, and a co-expression rate (CoER) in each bin was calculated. In
      all datasets, a higher CoER was obtained in a short CD range than a long distance
      range. These results show that across all studied species, there was a consistent
      effect of CD on co-expression. However, the results using the ND show more
      diversity. Intra- and inter-species comparisons of CoER reveal that there are
      significant differences in the co-expression rates of neighboring genes among the
      species. A pair-wise BLAST analysis finds 8-30 % of the highly co-expressed pairs
      are duplicated genes. CONCLUSION: We confirmed that in the six eukaryotic
      species, there was a consistent tendency that neighboring genes are likely to be
      co-expressed. Results of pair-wised BLAST indicate a significant effect of non
      duplicated pairs on co-expression. A comparison of CD and ND suggests the
      dominant effect of CD.

PMID- 14718067
TI  - Low-pass sequencing for microbial comparative genomics.
AB  - BACKGROUND: We studied four extremely halophilic archaea by low-pass shotgun
      sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non
      pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and
      (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand
      single pass genomic sequences per genome were obtained. The data were analyzed by
      comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome
      as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid
      approach that can readily be performed on any cultured microbe. RESULTS: As
      expected, the four archaeal halophiles analyzed exhibit both bacterial and
      eukaryotic characteristics as well as uniquely archaeal traits. All five
      halophiles exhibit greater than sixty percent GC content and low isoelectric
      points (pI) for their predicted proteins. Multiple insertion sequence (IS)
      elements, often involved in genome rearrangements, were identified in H.
      lacusprofundi and H. marismortui. The core biological functions that govern
      cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these
      four other halophiles. Multiple TATA box binding protein (TBP) and transcription
      factor IIB (TFB) homologs were identified from most of the four shotgunned
      halophiles. The reconstructed molecular tree of all five halophiles shows a large
      divergence between these species, but with the closest relationship being between
      H. sp. NRC-1 and H. lacusprofundi. CONCLUSION: Despite the diverse habitats of
      these species, all five halophiles share (1) high GC content and (2) low protein
      isoelectric points, which are characteristics associated with environmental
      exposure to UV radiation and hypersalinity, respectively. Identification of
      multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest
      that genome structure and dynamic genome reorganization might be similar to that
      previously observed in the IS-element rich genome of H. sp. NRC-1. Identification
      of multiple TBP and TFB homologs in these four halophiles are consistent with the
      hypothesis that different types of complex transcriptional regulation may occur
      through multiple TBP-TFB combinations in response to rapidly changing
      environmental conditions. Low-pass shotgun sequence analyses of genomes permit
      extensive and diverse analyses, and should be generally useful for comparative
      microbial genomics.

PMID- 14718068
TI  - Three-parameter lognormal distribution ubiquitously found in cDNA microarray data
      and its application to parametric data treatment.
AB  - BACKGROUND: To cancel experimental variations, microarray data must be normalized
      prior to analysis. Where an appropriate model for statistical data distribution
      is available, a parametric method can normalize a group of data sets that have
      common distributions. Although such models have been proposed for microarray
      data, they have not always fit the distribution of real data and thus have been
      inappropriate for normalization. Consequently, microarray data in most cases have
      been normalized with non-parametric methods that adjust data in a pair-wise
      manner. However, data analysis and the integration of resultant knowledge among
      experiments have been difficult, since such normalization concepts lack a
      universal standard. RESULTS: A three-parameter lognormal distribution model was
      tested on over 300 sets of microarray data. The model treats the hybridization
      background, which is difficult to identify from images of hybridization, as one
      of the parameters. A rigorous coincidence of the model to data sets was found,
      proving the model's appropriateness for microarray data. In fact, a closer
      fitting to Northern analysis was obtained. The model showed inconsistency only at
      very strong or weak data intensities. Measurement of z-scores as well as
      calculated ratios was reproducible only among data in the model-consistent
      intensity range; also, the ratios were independent of signal intensity at the
      corresponding range. CONCLUSION: The model could provide a universal standard for
      data, simplifying data analysis and knowledge integration. It was deduced that
      the ranges of inconsistency were caused by experimental errors or additive noise
      in the data; therefore, excluding the data corresponding to those marginal ranges
      will prevent misleading analytical conclusions.

PMID- 14718077
TI  - Risks and benefits of preexposure and postexposure smallpox vaccination.
AB  - This article presents a model and decision criteria for evaluating a person's
      risk of pre- or postexposure smallpox vaccination in light of serious vaccine
      related adverse events (death, postvaccine encephalitis and progressive
      vaccinia). Even at a 1-in-10 risk of 1,000 initial smallpox cases, a person in a
      population of 280 million has a greater risk for serious vaccine-related adverse
      events than a risk for smallpox. For a healthcare worker to accept preexposure
      vaccination, the risk for contact with an infectious smallpox case-patient must
      be >1 in 100, and the probability of 1,000 initial cases must be >1 in 1,000. A
      member of an investigation team would accept preexposure vaccination if his or
      her anticipated risk of contact is 1 in 2.5 and the risk of attack is assumed to
      be >1 in 16,000. The only circumstances in which postexposure vaccination would
      not be accepted are the following: if vaccine efficacy were <1%, the risk of
      transmission were <1%, and (simultaneously) the risk for serious vaccine-related
      adverse events were >1 in 5,000.

PMID- 14718078
TI  - Toxoplasma gondii infection in the United States, 1999-2000.
AB  - Infection with Toxoplasma gondii can lead to congenital and acquired disease,
      resulting in loss of vision and neurologic illness. We tested sera collected in
      the National Health and Examination Survey (NHANES) from 1999-2000 for T. gondii
      specific immunoglobulin G antibodies and compared these results with results from
      sera obtained in the NHANES III survey (1988-1994). NHANES collects data on a
      nationally representative sample of the U.S. civilian population. Of 4,234
      persons 12-49 years of age in NHANES 1999-2000, 15.8= (age-adjusted, 95%
      confidence limits [CL] 13.5, 18.1) were antibody positive; among women (n =
      2,221) 14.9= (age-adjusted, 95% CL 12.5, 17.4) were antibody positive. T. gondii
      antibody prevalence was higher among non-Hispanic black persons than among non
      Hispanic white persons (age-adjusted prevalence 19.2% vs. 12.1%, p = 0.003) and
      increased with age. No statistically significant differences were found between
      T. gondii antibody prevalence in NHANES 1999-2000, and NHANES III. T. gondii
      antibody prevalence has remained stable over the past 10 years in the United
      States.

PMID- 14718079
TI  - Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute
      respiratory syndrome mortality.
AB  - Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A
      novel coronavirus is deemed to be the causative agent. Early diagnosis can be
      made with reverse transcriptase-polymerase chain reaction (RT-PCR) of
      nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62
      SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR
      positive patients had significantly more shortness of breath, a lower lymphocyte
      count, and a lower lactate dehydrogenase level; they were also more likely to
      have bilateral and multifocal chest radiograph involvement, to be admitted to
      intensive care, to need mechanical ventilation, and to have higher mortality
      rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate
      samples was an independent predictor of death within 30 days.

PMID- 14718080
TI  - West Nile virus infection in nonhuman primate breeding colony, concurrent with
      human epidemic, southern Louisiana.
AB  - During the summer of 2002, an epidemic of West Nile meningoencephalitis occurred
      in southern Louisiana. Following the outbreak, blood samples were collected from
      1,692 captive rhesus monkeys (Macaca mulatta), pigtail macaques (M. nemestrina),
      and baboons (Papio spp.) that were permanently housed outdoors at a nonhuman
      primate breeding facility in St. Tammany Parish, Louisiana. The serum samples
      were examined for antibodies to West Nile virus (WNV). Overall, 36% of the
      captive nonhuman primates had WNV antibodies; comparison of these samples with
      banked serum samples from previous blood collections indicated that the animals
      were infected subclinically from February to August 2002. WNV activity was
      demonstrated in surveillance at the nonhuman primate-breeding colony and in the
      neighboring community during this same period. The high infection rate in this
      captive nonhuman primate population illustrates the intensity of WNV transmission
      that can occur silently in nature among other susceptible vertebrates during
      epidemic periods.

PMID- 14718081
TI  - Human hantavirus infections, Sweden.
AB  - The prevalent human hantavirus disease in Sweden is nephropathia epidemica, which
      is caused by Puumala virus and shed by infected bank voles (Clethrionomys
      glareolus). To evaluate temporal and spatial patterns of this disease, we studied
      2,468 reported cases from a highly disease-endemic region in northern Sweden. We
      found that, in particular, middle-aged men living in rural dwellings near coastal
      areas were overrepresented. The case-patients were most often infected in late
      autumn, when engaged in activities near or within manmade rodent refuges. Of 862
      case-patients confident about the site of virus exposure, 50% were concentrated
      within 5% of the study area. The incidence of nephropathia epidemica was
      significantly correlated with bank vole numbers within monitored rodent
      populations in part of the region. Understanding this relationship may help
      forestall future human hantavirus outbreaks.

PMID- 14718082
TI  - Fatal spotted fever rickettsiosis, Minas Gerais, Brazil.
AB  - The emergence and reemergence of a serious infectious disease are often
      associated with a high case-fatality rate because of misdiagnosis and
      inappropriate or delayed treatment. The current reemergence of spotted fever
      rickettsiosis caused by Rickettsia rickettsii in Brazil has resulted in a high
      proportion of fatal cases. We describe two familial clusters of Brazilian spotted
      fever in the state of Minas Gerais, involving six children 9 months to 15 years
      of age; five died. Immunohistochemical investigation of tissues obtained at
      necropsy of a child in each location, Novo Cruzeiro and Coronel Fabriciano
      municipalities, established the diagnosis by demonstration of disseminated
      endothelial infection with spotted fever group rickettsiae. The diagnosis in the
      two fatal cases from Coronel Fabriciano and the surviving patient from Novo
      Cruzeiro was further supported by immunofluorescence serologic tests.

PMID- 14718083
TI  - Rapid antigen-capture assay to detect West Nile virus in dead corvids.
AB  - The utility of the VecTest antigen-capture assay to detect West Nile virus (WNV)
      in field-collected dead corvids was evaluated in Manitoba and Ontario, Canada, in
      2001 and 2002. Swabs were taken from the oropharynx, cloaca, or both of 109
      American Crows, 31 Blue Jays, 6 Common Ravens, and 4 Black-billed Magpies from
      Manitoba, and 255 American Crows and 28 Blue Jays from Ontario. The sensitivity
      and specificity of the antigen-capture assay were greatest for samples from
      American Crows; oropharyngeal swabs were more sensitive than cloacal swabs, and
      interlaboratory variation in the results was minimal. The sensitivity and
      specificity of the VecTest using oropharyngeal swabs from crows were 83.9% and
      93.6%, respectively, for Manitoba samples and 83.3% and 95.8%, respectively, for
      Ontario birds. The VecTest antigen-capture assay on oropharyngeal secretions from
      crows is a reliable and rapid diagnostic test that appears suitable for
      incorporation into a WNV surveillance program.

PMID- 14718084
TI  - Serologic evidence of dengue infection before onset of epidemic, Bangladesh.
AB  - Dengue fever emerged in Bangladesh in 2000. We tested 225 serum samples from
      febrile patients and 184 blood donors in 1996 and 1997 for dengue antibodies; 55
      (24.4% ) febrile patients had dengue antibodies ( 65.5% with secondary infection
      pattern), compared with one (0.54%) donor (p <0.001), suggesting that dengue
      transmission was ongoing well before 1996.

PMID- 14718085
TI  - Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in
      hospitalized patients.
AB  - To determine whether fluoroquinolone exposure is a risk factor for the isolation
      of Staphylococcus aureus and whether the effect is different for methicillin
      resistant S. aureus (MRSA) versus methicillin--susceptible S. aureus (MSSA), we
      studied two case groups. The first case group included 222 patients with
      nosocomially acquired MRSA. The second case group included 163 patients with
      nosocomially acquired MSSA. A total of 343 patients admitted concurrently served
      as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of
      MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR
      5.4; p <0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with
      isolation of MRSA but not MSSA. After adjustment for multiple variables, both
      drugs remained risk factors for MRSA (levofloxacin OR 3.4; p <0.0001;
      ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or
      ciprofloxacin is a significant risk factor for the isolation of MRSA, but not
      MSSA.

PMID- 14718086
TI  - Genetic variation among temporally and geographically distinct West Nile virus
      isolates, United States, 2001, 2002.
AB  - Analysis of partial nucleotide sequences of 22 West Nile virus (WNV) isolates
      collected during the summer and fall of 2001 and 2002 indicated genetic variation
      among strains circulating in geographically distinct regions of the United States
      and continued divergence from isolates collected in the northeastern United
      States during 1999 and 2000. Sequence analysis of a 2,004-nucleotide region
      showed that 14 isolates shared two nucleotide mutations and one amino acid
      substitution when they were compared with the prototype WN-NY99 strain, with 10
      of these isolates sharing an additional nucleotide mutation. In comparison,
      isolates collected from coastal regions of southeast Texas shared the following
      differences from WN-NY99: five nucleotide mutations and one amino acid
      substitution. The maximum nucleotide divergence of the 22 isolates from WN-NY99
      was 0.35% (mean = 0.18%). These results show the geographic clustering of
      genetically similar WNV isolates and the possible emergence of a dominant variant
      circulating across much of the United States during 2002.

PMID- 14718087
TI  - Ebola hemorrhagic fever transmission and risk factors of contacts, Uganda.
AB  - From August 2000 through January 2001, a large epidemic of Ebola hemorrhagic
      fever occurred in Uganda, with 425 cases and 224 deaths. Starting from three
      laboratory-confirmed cases, we traced the chains of transmission for three
      generations, until we reached the primary case-patients (i.e., persons with an
      unidentified source of infection). We then prospectively identified the other
      contacts in whom the disease had developed. To identify the risk factors
      associated with transmission, we interviewed both healthy and ill contacts (or
      their proxies)who had been reported by the case-patients (or their proxies) and
      who met the criteria set for contact tracing during surveillance. The patterns of
      exposure of 24 case-patients and 65 healthy contacts were defined, and crude and
      adjusted prevalence proportion ratios (PPR) were estimated for different types of
      exposure. Contact with the patient's body fluids (PPR = 4.61%, 95% confidence
      interval 1.73 to 12.29) was the strongest risk factor, although transmission
      through fomites also seems possible.

PMID- 14718088
TI  - Hantavirus pulmonary syndrome, southern Chile.
AB  - We analyzed data from 25 consecutive patients with hantavirus pulmonary syndrome
      (HPS) admitted to the Puerto Montt and Osorno Regional Hospitals, southern Chile,
      from 1997 to 2001, emphasizing epidemiologic, clinical, radiographic, treatment,
      and laboratory aspects. Hemorrhage was frequent (64%), and 48% of patients showed
      alterations in renal function. Ten patients died (40%). We identified three
      groups of patients, which included the following: 1) those with the least severe
      form who had prodromic symptoms without pulmonary involvement; 2) those with
      moderate illness who had interstitial pulmonary infiltrates, usually needed
      supplemental nasal oxygen, were hemodynamically stable, and had an APACHE II <12
      (none of whom died); and 3) those with the severe form who required mechanical
      ventilation, frequently had hemodynamic instability (93%), experienced a high
      mortality rate (77%), and had an APACHE II >12. Mild forms of HPS also exist,
      which are poorly known; the symptoms could be confounded with those of other
      viral diseases, leading to underdiagnosis.

PMID- 14718089
TI  - Triosephosphate isomerase gene characterization and potential zoonotic
      transmission of Giardia duodenalis.
AB  - To address the source of infection in humans and public health importance of
      Giardia duodenalis parasites from animals, nucleotide sequences of the
      triosephosphate isomerase (TPI) gene were generated for 37 human isolates, 15 dog
      isolates, 8 muskrat isolates, 7 isolates each from cattle and beavers, and 1
      isolate each from a rat and a rabbit. Distinct genotypes were found in humans,
      cattle, beavers, dogs, muskrats, and rats. TPI and small subunit ribosomal RNA
      (SSU rRNA) gene sequences of G. microti from muskrats were also generated and
      analyzed. Phylogenetic analysis on the TPI sequences confirmed the formation of
      distinct groups. Nevertheless, a major group (assemblage B) contained most of the
      human and muskrat isolates, all beaver isolates, and the rabbit isolate. These
      data confirm that G. duodenalis from certain animals can potentially infect
      humans and should be useful in the detection, differentiation, and taxonomy of
      Giardia spp.

PMID- 14718090
TI  - Severe acute respiratory syndrome-associated coronavirus infection.
AB  - Whether severe acute respiratory syndrome-associated coronavirus (SARS-CoV)
      infection can be asymptomatic is unclear. We examined the seroprevalence of SARS
      CoV among 674 healthcare workers from a hospital in which a SARS outbreak had
      occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321
      (48%) were asymptomatic throughout the course of these observations. None of
      these healthcare workers had antibody to SARS CoV, indicating that subclinical or
      mild infection attributable to SARS-CoV in adults is rare.

PMID- 14718091
TI  - Fluoroquinolone resistance linked to GyrA, GyrB, and ParC mutations in Salmonella
      enterica typhimurium isolates in humans.
AB  - We report two cases of infection with clonally unrelated, high-level
      ciprofloxacin-resistant, b-lactamase-producing strains of Salmonella enterica
      Typhimurium. Resistance was caused by four topoisomerase mutations, in GyrA,
      GyrB, and ParC and increased drug efflux. Ciprofloxacin treatment failed in one
      case. In the second case, reduced susceptibility to third-generation
      cephalosporins occurred after initial treatment with these drugs and may explain
      the treatment failure with ceftriaxone.

PMID- 14718092
TI  - Cowpox with severe generalized eruption, Finland.
AB  - Cowpox with a severe, generalized eruption was diagnosed in an atopic 4-year-old
      girl by electron microscopy, virus isolation, polymerase chain reaction, and
      immunoglobulin (Ig) M and low-avidity IgG antibodies. The hemagglutinin gene of
      the isolate clustered with a Russian cowpox virus strain, and more distantly,
      with other cowpox and vaccinia virus strains. The patient's dog had orthopoxvirus
      specific antibodies, indicating a possible transmission route. In Finnish wild
      rodents, orthopoxvirus seroprevalences were 0%-92%, in humans the seroprevalence
      was 100% in the age group >50, decreasing towards younger age groups.

PMID- 14718093
TI  - Pulmonary tuberculosis due to Mycobacterium bovis subsp. caprae in captive
      Siberian tiger.
AB  - We report the first case of pulmonary tuberculosis caused by Mycobacterium bovis
      subsp. caprae in a captive Siberian tiger, an endangered feline. The pathogen was
      isolated from a tracheal aspirate obtained by bronchoscopy. This procedure
      provided a reliable in vivo diagnostic method in conjunction with conventional
      and molecular tests for the detection of mycobacteria.

PMID- 14718094
TI  - Dengue-1 virus isolation during first dengue fever outbreak on Easter Island,
      Chile.
AB  - Dengue virus was detected for the first time in Chile, in an outbreak of dengue
      fever on Easter Island. The virus was isolated in tissue culture and
      characterized by reverse transcription-polymerase chain reaction as being dengue
      type 1.

PMID- 14718095
TI  - Flow cytometry and T-cell response monitoring after smallpox vaccination.
AB  - Orthopoxvirus zoonosis or smallpox as result of bioterrorism or biological
      warfare represents a risk for epidemic spread. By monitoring T-cell responses by
      flow cytometry, we observed a recall response after recent vaccination against
      smallpox. When the high similarity between the orthopoxviruses is considered,
      this rapid assay that uses vaccinia antigens could identify recently exposures.

PMID- 14718096
TI  - Shigella dysenteriae serotype 1, Kolkata, India.
AB  - Since July 2002, bacteriologically confirmed shigellosis cases have increased,
      and multidrug-resistant Shigella dysenteriae serotype 1 strains have reemerged in
      patients hospitalized with diarrhea in Kolkata, India. The isolated strains of S.
      dysenteriae 1 showed resistance to chloramphenicol (80%), ampicillin (100%),
      tetracycline (100%), co-trimoxazole (100%), nalidixic acid (100%), norfloxacin
      (100%), and ciprofloxacin (100%). Emergence of fluoroquinolone resistance in S.
      dysenteriae 1 strains complicated treatment of shigellosis patients. Six strains
      belonging to provisional serovars of S. dysenteriae were also identified for the
      first time in patients hospitalized with diarrhea in Kolkata, India.

PMID- 14718097
TI  - Levofloxacin treatment failure in Haemophilus influenzae pneumonia.
AB  - We describe the first case of failure of oral levofloxacin treatment of community
      acquired pneumonia caused by Haemophilus influenzae. The strain showed cross
      resistance to fluoroquinolones and carried four mutations in quinolone resistance
      determining regions of DNA gyrase and topoisomerase IV genes.

PMID- 14718098
TI  - Fluoroquinolone susceptibility of Campylobacter strains, Senegal.
AB  - To assess fluoroquinolone susceptibility of Campylobacter strains in Senegal,
      skin samples were collected from 250 chicken carcasses from January 2001 to
      October 2002. Among 205 isolated Campylobacter strains, 59% and 41% were
      identified as Campylobacter jejuni and C. coli, respectively; the overall
      ciprofloxacin-resistance rate was 34%.

PMID- 14718099
TI  - Fluoroquinolone resistance in Campylobacter absent from isolates, Australia.
AB  - Fluoroquinolone resistance was detected in 12 of 370 Australian human
      Campylobacter isolates; 10 of these were travel-associated, and for 2 isolates
      travel status was unknown. No resistance was found in isolates known to be
      locally acquired. In Australia, fluoroquinolones have not been licensed for use
      in food production animals, a policy that may have relevance for countries with
      fluoroquinolone-resistant Campylobacter.

PMID- 14718100
TI  - Polymerase chain reaction assay and bacterial meningitis surveillance in remote
      areas, Niger.
AB  - To compensate for the lack of laboratories in remote areas, the national
      reference laboratory for meningitis in Niger used polymerase chain reaction (PCR)
      to enhance the surveillance of meningitis caused by Neisseria meningitidis,
      Streptococcus pneumoniae, and Haemophilus influenzae. PCR effectively documented
      the wide geographic spread of N. meningitidis serogroup W135.

PMID- 14718101
TI  - [Triple immunosuppressive therapy in the treatment of severe ulcerative colitis].
AB  - INTRODUCTION: Severe episodes of steroid-refractory ulcerative colitis (UC) were
      considered an indication for surgery until the introduction of new
      immunosuppressive agents such as cyclosporine. OBJECTIVES: 1) To confirm the
      efficacy of intravenous cyclosporine in inducing remission in severe episodes of
      steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive
      therapy with cyclosporine, azathioprine and prednisone in the maintenance of
      remission induced by intravenous cyclosporine. PATIENTS AND METHOD: Fourteen
      patients diagnosed with a severe episode of steroid-refractory UC were treated
      with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after
      response was induced, this regimen was substituted by oral cyclosporine plus
      azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids.
      Neoral cyclosporine was progressively reduced until discontinuation within 3
      months, coinciding with a simultaneous decrease of oral steroids. RESULTS: All
      patients showed response to intravenous cyclosporine with a significant reduction
      in the Truelove index calculated before and after treatment. After remission was
      induced, all patients followed triple immunosuppressive therapy for 3 months. In
      the follow-up for a mean of 24 months (range: 14-34) only two patients required
      admission for a new episode of UC and colectomy was finally indicated in only
      one. None of the 14 patients treated with cyclosporine showed severe adverse
      effects attributable to the drug. CONCLUSIONS: Intravenous cyclosporine is a safe
      and effective alternative in the treatment of severe episodes of steroid
      refractory UC. Early initiation of oral administration associated with
      azathioprine is useful in maintaining response, reducing subsequent relapses and
      the need for colectomy during the follow-up of these patients.

PMID- 14718102
TI  - [Dilatation of the papilla of Vater in the treatment of choledocholithiasis in
      selected patients].
AB  - OBJECTIVE: To prospectively analyze the results obtained with papillary balloon
      dilatation (PBD) in the treatment of common bile duct stones in patients at risk
      of complications if endoscopic sphincterotomy (ES) were performed. PATIENTS AND
      METHOD: Thirty-three patients were included between January 2001 and June 2003
      (mean age 76.2 years). The criteria for PBD were: choledocholithiasis < or =10 mm
      in patients with peripapillary diverticula, hemostatic alterations, Billroth-II,
      and preservation of Oddi's sphincter. In 79% of the patients sedation was
      performed by an anesthetist. PBD was performed with a balloon catheter dilator
      with a diameter of 8 or 10 mm for 2 minutes. The efficacy and duration of the
      procedure as well as complications at 30 days and patient satisfaction were
      evaluated. RESULTS: Stone extraction was achieved in all patients (100%). The
      mean duration of the procedure was 26 minutes. Two patients (6%) presented mild
      pancreatitis. Serum amylase was elevated in 16 patients (48%): > or =3 times
      (post-PBD hyperamylasemia) in 11 (33%). The procedure caused no discomfort in
      25/26 (96%) of the patients sedated by an anesthetist vs 2/5 patients (49%) who
      underwent endoscopic sedation. CONCLUSIONS: PBD is an effective and simple
      therapeutic option in the treatment of small common bile duct stones (< or =10
      mm) and in patients at high risk. The duration of endoscopic retrograde
      cholangiopancreatography is not prolonged. Complications are infrequent (6%) and
      mild. Post-PBD hyperamylasemia is frequent and generally without clinical
      importance. Sedation by an anesthetist improves patient satisfaction.

PMID- 14718103
TI  - [Treatment modalities in patients with hepatocellular carcinoma: a retrospective
      series in a single institution in Mexico].
AB  - BACKGROUND: To date, curative treatment options for hepatocellular carcinoma
      (HCC) include orthotopic liver transplantation or surgical resection. Most
      patients are detected with nonresectable or transplantable HCC due to disease
      extension or comorbid factors, and are therefore candidates for palliative
      treatments only. Few follow-up data are available in patients with HCC in Latin
      America. We therefore reviewed the experience of HCC treatment in a single
      institution over a 10-year period. PATIENTS AND METHOD: A total of 135 patients
      attending the Instituto Nacional de Ciencias Medicas y Nutricion Salvador
      Zubiran, a national referral center in Mexico, from January 1991 to December 2000
      were included. In all patients etiology, stage, and diagnostic and therapeutic
      measures were documented. Survival time was calculated as a function of staging
      and therapy. RESULTS: Of 135 patients, 77 (57%) were men and 58 (43%) were women.
      The mean age at diagnosis was 59.17 years (range: 16-87 years). Cirrhosis was
      diagnosed in 89 patients (64.4%). The median overall survival for all patients
      with HCC was 7.9 months. Treatment included surgical resection (n=22), hepatic
      artery chemoembolization (n=10), percutaneous ethanol injection (n=6), systemic
      chemotherapy (n=5), tamoxifen (n=11), and thalidomide (n=1). Eighty patients
      received support measures. The median survival in the group of patients who
      underwent surgical resection (37.89 months) was significantly higher than that in
      the groups of patients who did not undergo resection. CONCLUSIONS: Patients with
      HCC who received no treatment had a median survival of 1.7 months. Hepatic
      resection offers the best chance of cure in patients with HCC. The strong
      association between HCC and cirrhotic liver disease makes surgical resection
      difficult in patients with low hepatic reserve.

PMID- 14718104
TI  - [Indomethacin-induced ileal perforation].
AB  - We present two cases of indomethacin-induced perforation of the distal small
      intestine. Both patients were male and undergoing oral indomethacin therapy. Both
      presented acute abdomen with diffuse peritonitis secondary to perforations
      located in the antimesenteric border of the terminal ileum. Histopathological
      lesions of the intestinal wall showed transmural infiltration, congestion, and
      hemorrhage; their severity was related to higher doses and longer duration of
      indomethacin therapy.

PMID- 14718105
TI  - [Colonic spirochetes: an infrequent cause of adult diarrhea].
AB  - Large intestine infection due to spirochetes was described in 1967 and is mainly
      related to two pathogens, Serpulina pilosicoli and Brachyspira aalborgi.
      Clinically, infection presents as diarrhea and/or rectorrhagia and is more
      frequent among homosexuals. Its prevalence is difficult to estimate but
      significant differences have been described according to the socioeconomic level
      of the area studied. We describe three cases of diarrhea due to spirochetes,
      which are of interest due to the lack of published cases in Spain. Based on these
      cases, we describe the main characteristics (morphological, therapeutic, etc.) of
      this infection.

PMID- 14718106
TI  - [Treatment of hepatitis C in nonresponders to ribavirin and/or interferon].

PMID- 14718107
TI  - [Hereditary pancreatitis].

PMID- 14718108
TI  - [The MELD system and organ allocation policy: lessons after the first year of use
      in the United States].

PMID- 14718110
TI  - [Estimation of survival with the MELD prognostic model].

PMID- 14718109
TI  - [Literature searches: a systematic method leads to success].

PMID- 14718111
TI  - [Hepatic angiomyolipoma in a woman with tuberous sclerosis].

PMID- 14718112
TI  - [Acute appendicitis as onset of generalized tuberculosis].

PMID- 14718113
TI  - [Tobacco use in childhood and adolescence].

PMID- 14718114
TI  - [A survey on the relationship between tobacco use and physical exercise among
      university students].
AB  - OBJECTIVE: To determine the prevalence of tobacco use among university students
      who participate in sports activities. MATERIALS AND METHODS This was a
      descriptive, cross-sectional study based on a self-administered questionnaire
      completed by students who participated in activities at a university sports
      center. The variables studied were age, sex, tobacco use, cigarettes/day, prior
      history of physical exercise, awareness of the regulations concerning tobacco use
      in force on the university campus, opinion on the relationship between smoking
      and reduced physical performance, and desire to quit smoking. RESULTS: A total of
      406 completed questionnaires were received (41.2% of the target population);
      71.7% were from women and 28.3% from men. The mean (SD) age of the sample was 22
      (3.6) years, and the prevalence of smoking was 30.3%. The mean number of
      cigarettes smoked per day was 10.5 (6.7) for the sample as a whole, 9.3 (6.1) for
      women, and 14.7 (7.4) for men; the differences were statistically significant. No
      significant differences were found with respect to the relationship between
      exercise and tobacco use. A total of 98.8% of the subjects were of the opinion
      that smoking reduced physical performance, and 46.3% expressed a desire to quit.
      CONCLUSIONS: The practice of physical exercise during adolescence as part of a
      prevention program might interfere with the factors that lead young people to
      start smoking and thereby contribute to a reduction in the prevalence of tobacco
      use in the population as a whole.

PMID- 14718115
TI  - [Tobacco use among young people in informal education settings: a survey of
      behaviors and opinions].
AB  - OBJECTIVES: To obtain information about the tobacco use of young people in an
      informal educational setting. To analyze the profile of the young smoker and the
      associated social and health factors, and to discover the opinion of tobacco held
      by smokers and non-smokers. POPULATION AND METHODS An anonymous, self
      administered, personal questionnaire was completed by volunteers aged 14 to 26
      years old taking part in the activities of 3 youth centers. The questionnaire
      included items about the subjects' smoking habits, their awareness of the harmful
      effects of cigarette smoking and knowledge of tobacco cessation techniques. The
      survey also covered the health and social profile of young smokers. RESULTS: A
      total of 84 completed questionnaires were received (40 males and 44 females). The
      mean age of the sample was 18.3 years. Of the total, 15.4% had never smoked, 44%
      described themselves as smokers, and 16.6% as ex-smokers. Of the smokers, 40%
      smoked up to 10 cigarettes/day and 60% between 11 and 20. The age of initiation
      or experimentation was 13.1 years, and that of the onset of regular or daily use,
      14.6 years. Only 23.5% of the smokers expressed a desire to stop smoking, and 50%
      had never tried to quit. Tobacco use was associated with weekend alcohol
      consumption in 59% of the smokers. None of the respondents were aware of the
      tobacco cessation aids and therapies available. CONCLUSIONS: According to the
      data collected by way of these questionnaires, a high percentage of the young
      people who participate in these leisure activities are smokers. They report a
      very early age of initiation and an accurate understanding of the serious
      consequences of tobacco use. Their lack of awareness about the available aids for
      tobacco cessation is a cause for concern, and the number of smokers who expressed
      a desire to quit was minimal. A disturbing increase in the association between
      alcohol and tobacco consumption was observed.

PMID- 14718116
TI  - [Video-assisted thoracoscopic sympathectomy for the treatment of facial flushing:
      ultrasonic scalpel versus diathermy].
AB  - OBJECTIVE: To evaluate the advantages of the ultrasonic scalpel compared to
      electrocoagulation in patients undergoing video-assisted thoracoscopic
      sympatholysis or sympathectomy for uncontrolled facial blushing. METHODS: Two
      hundred bilateral video-assisted thoracoscopic procedures to interrupt
      transmission in the thoracic sympathetic nerve were performed in 100 patients
      with incapacitating facial blushing. In 2 cases, the video-assisted approach was
      chosen because of pleural symphysis. The mean age of patients was 34 years
      (range: 15 to 67). The sympathetic chain was interrupted from the lower portion
      of the first thoracic ganglion through the third. RESULTS: All patients were
      discharged within 24 hours with the exception of one on whom an emergency
      thoracotomy had been performed. No complications were reported in the group in
      which a harmonic scalpel was used. One case of temporary Horner syndrome (4
      months) and 3 cases of persistent chest pain (more than 2 weeks) were reported in
      the diathermy group. There were 9 cases of partial and asymptomatic pneumothorax
      that resolved without treatment or prolonged hospital stays. CONCLUSION:
      Dissection of the sympathetic nerve is accomplished more reliably and with better
      visualization with the ultrasonic scalpel. Peripheral lesions in lung parenchyma
      and adjacent tissues (intercostal vessels and nerves) are avoided, as is Horner
      syndrome, which can be caused by dispersion of heat. Use of the ultrasonic
      scalpel would also lead to a lower incidence of postoperative neuralgia.

PMID- 14718118
TI  - [Fatal or near-fatal asthma: clinical entity or incorrect management?].

PMID- 14718117
TI  - [Effects of muscle training on breathing pattern in patients with severe chronic
      obstructive pulmonary disease].
AB  - OBJECTIVE: During physical exertion, the ventilatory response of patients with
      severe chronic obstructive pulmonary disease (COPD) is more rapid and shallow
      than that of healthy subjects. There is evidence that exercise training can alter
      breathing pattern in COPD patients. The purpose of the present study was to
      observe the effects of physical training on patients with severe COPD and to
      determine whether or not any possible changes were maintained over time. MATERIAL
      AND METHODS: Patients with severe COPD without bronchial reversibility were
      enrolled in a randomized controlled trial of a peripheral muscle training program
      carried out in a hospital setting. All enrolled patients were clinically stable,
      without exacerbation, and were randomly assigned to a training program of high
      (group A) or low (group B) intensity. RESULTS: Thirty-five men with severe COPD
      in stable condition (mean [SD] forced expiratory volume in 1 second at 41%[7%])
      were enrolled in the study. The mean age was 64(5) years. Group A underwent
      training at 70(22) W and group B at 35(10) W, such that the estimated total work
      was 8050(2882) kJ in group A and 4044(1205) kJ in group B. Breathing pattern
      changes were detected in exercise tests only for group A patients, but the
      changes were not maintained 12 months after the end of the program. CONCLUSIONS:
      Intense training produces changes in the breathing pattern of patients with
      severe COPD. The changes are not specific to the task performed, not dependent on
      lactate production, and not maintained over the long term.

PMID- 14718119
TI  - [Sleep-disordered breathing and cerebrovascular disease].

PMID- 14718120
TI  - [Spirometry at home: technology within the patient's reach].
AB  - Spirometry is a basic lung function test useful both for measuring and for
      monitoring expiratory volume. For many years monitoring has been performed by
      means of a portable peak flow meter capable of measuring maximal expiratory flow.
      We present a portable spirometer (Spirotel, Medical International Research, Rome,
      Italy) capable of transmitting stored lung function data from the patient's home
      by telephone. The device is easy to use, presents information graphically and
      numerically, and allows degrees of change in lung function to be monitored on
      line. It may be useful for controlling asthma and work-related respiratory
      diseases.

PMID- 14718121
TI  - [Polyradiculitis and Wegener's granulomatosis].
AB  - Wegener's granulomatosis is a systemic vasculitis of unknown etiology, primarily
      affecting the upper and lower respiratory tract and the kidneys, although there
      is a form restricted to the lungs. Wegener's granulomatosis occurs infrequently,
      with an estimated annual incidence of 8.5 cases per million. The principal
      symptoms at onset usually involve the upper and lower airway. The central nervous
      system is involved in approximately 22% of cases, but neurological signs occur
      infrequently among the initial clinical manifestations. Proteinase 3-specific
      antineutrophil cytoplasmic antibodies are useful serological markers for
      establishing a diagnosis, which should, however, be confirmed by a tissue biopsy
      of the affected organ.

PMID- 14718122
TI  - [Sarcoidosis following combined ribavirin and interferon therapy: a case report
      and review of the literature].
AB  - Treatment of active chronic viral hepatitis type C with interferon alpha has
      proved effective and therefore its use is being extended to a large number of
      patients. Common side effects include respiratory manifestations. One side effect
      attributable to the immunomodulatory effect of interferon is the possible
      triggering or exacerbation of systemic or cutaneous sarcoidosis. We report a new
      case and offer an exhaustive review of the literature. A 49-year-old man with
      type C chronic, active hepatitis developed new respiratory symptoms and pulmonary
      infiltrates with hilar and mediastinal adenopathy after 4 months of treatment
      with pegylated interferon and ribavirin. The transbronchial biopsy showed
      multiple sarcoid granulomas. When the patient was diagnosed, he had already taken
      the total dose of interferon and no specific treatment was started. His hepatitis
      did not respond to therapy and his viral load and transaminase levels remained
      high.

PMID- 14718123
TI  - [Study of delays in diagnosing symptomatic pulmonary tuberculosis].

PMID- 14718124
TI  - [Immigration and health].

PMID- 14718125
TI  - [Characteristics of immigrant women and their neonates].
AB  - BACKGROUND: Immigrant status is frequently assumed to constitute a health risk
      because migration is inevitably associated with a period of significant
      adjustment and stress. OBJECTIVE: To compare the social characteristics and
      perinatal outcomes of mothers who deliver in a third level hospital in Spain
      according to their socioeconomic level of the country of origin. METHODS: From
      December 2000 to March 2001, women who delivered were selected according to the
      socioeconomic status of their birth country. All women from low and middle income
      countries (immigrant mothers) and a sample (1:2) of those from high income
      countries (mainly Spanish-born mothers) completed a questionnaire on antenatal
      care, demographic and social characteristics, and country of birth and were
      followed-up to monitor neonatal clinical features. RESULTS: During the three
      months of the study, 203/1352 (15 %, CI 13.2-17.1) of the delivering mothers were
      immigrants. Most were from Central and South America (56 %, CI 49-62). Prenatal
      care was appropriate in most of the women (in 92.1 % of immigrant mothers and in
      96.8 % of Spanish mothers, p 5 0.01). The proportions of premature births, low
      birth weight and very-low birth weight showed no statistically significant
      differences between immigrant and Spanish mothers (15 vs. 10.6, 6.4 vs. 9.4, and
      2.1 vs. 1.5, respectively, p > 0.05 in all comparisons). Perinatal complications,
      including an Apgar score < or = 6, and the need for admission to the neonatal
      unit or to the intensive or intermediate care units, were not more frequent in
      the newborns of immigrant mothers. Immigrant women had less social or family
      support after delivery and maternity leave was much less frequent (62 % vs. 90 %,
      p < 0.001). CONCLUSIONS: Most of the immigrant women had healthy pregnancies and
      healthy birth outcomes. Perinatal complications do not seem to be more frequent
      among immigrant women. Differences were found in social support. To improve the
      health of these children, social support to immigrant women and their children
      should be intensified.

PMID- 14718126
TI  - [Socioeconomic determinants in immigrant families].
AB  - INTRODUCTION: In the last few years, the number of immigrant families in Spain
      has greatly increased, which has challenged healthcare services and posed new
      health problems. OBJECTIVES: To determine the main social risk factors present in
      an immigrant population group in order to take active measures to ensure the
      appropriate development of children in this population. METHODS: A descriptive
      cross-sectional study consisting of interviews with 179 foreign women with
      children under 1 year of age attending a public healthcare program. RESULTS: Most
      of the women were from Latin America (80 %), 11 % were from Morocco, and the
      remaining women were from other countries. A total of 14.5 % had university
      studies. In general, the women worked in domestic service and only 36 % had the
      documents required to live in Spain. Fifty-five percent of the women had lost
      their jobs because of their pregnancy. Most of the families lived in apartments
      with an average of 2.3 people per room, and 88 % shared their residence with
      other people. Twenty-five percent of the women had their first child before the
      age of 18 years. Pregnancy was unwanted in 50 % of the women. Seventy-one percent
      of deliveries were normal, and 83 % of the women breast-fed their children.
      Ninety-eight percent of the children were correctly vaccinated and 95 % visited a
      pediatrician regularly. CONCLUSIONS: The immigrant population is concentrated in
      the most disadvantaged social strata. Measures that provide adequate social
      support and healthcare to this population should be established to encourage the
      appropriate development of their children

PMID- 14718127
TI  - [Comparative study of infectious diseases in immigrant children from various
      countries].
AB  - INTRODUCTION: Immigrants have a higher risk of contracting some infectious
      diseases. The aim of this study was to determine and compare the morbidity
      profile of immigrant children according to their country of origin. MATERIAL AND
      METHODS: We performed a descriptive study of all immigrants aged less than 14
      years old who attended the Tropical Medicine Unit of the Ramon y Cajal Hospital
      in Madrid between 1989 and 2001. RESULTS: A total of 170 children were included
      (73 % from Africa, 19 % from Latin America, and 5 % from Asia). Seventy-five
      percent had at least one infectious disease (78 % of Africans and 62 % of Latin
      Americans) and 27 % were co-infected (> 2 pathogenic agents). The proportion of
      healthy children was higher (p < 0.05) among Latin Americans (21 %) than among
      Africans (9 %). The most frequent infectious diseases were malaria (35 %),
      intestinal parasites (48 %), filariasis (23 %), and viral hepatitis (19 %).
      Malaria, filariasis and hepatitis were more frequent in Africans than in
      Americans (p < 0.05). Other helminthic infections (15 %) were more frequent in
      Americans. In both groups intestinal parasites and tuberculosis (6 %) were
      prevalent. Of the 36 (21 %) asymptomatic children, 53 % had at least one
      infectious disease. The most frequently diagnosed diseases in Africans were
      intestinal parasitosis (35 %), malaria (7 %), cured hepatitis B (15 %),
      filariasis (12 %) and superficial mycosis (4 %). The most frequent infectious
      diseases in Latin Americans were intestinal parasitosis (38 %) and visceral
      toxocariasis (25 %). CONCLUSIONS: Infectious diseases and co-infections are
      frequent in immigrant children, even in those who are asymptomatic. We propose
      screening of certain infectious diseases in these children according to their
      country of origin and their length of residence in Spain.

PMID- 14718129
TI  - [Maltreated gypsy children: social and health risk factors and high-priority
      health care needs].
AB  - OBJECTIVES: To determine the prevalence of maltreated gypsy children admitted to
      centers of protection, as well as their demographic characteristics, type of
      maltreatment, frequency of associated social and health risk factors, frequent
      health problems and whether there are differences between these children and the
      general population of maltreated children. PATIENTS AND METHODS: We performed a
      retrospective cross-sectional cohort study over an 8-year period (1995-2002). The
      social and health reports of the maltreated children admitted to protection
      centers were reviewed and those belonging to the gypsy ethnic group were
      included. Information collection, definition of concepts and health assessments
      were performed according to nationwide methodologies, studies and directives. A
      descriptive and comparative statistical study was performed. RESULTS: During the
      study period, 873 children were admitted, of whom 74 were from the gypsy ethnic
      group (a prevalence of 8.5 %, 1.7 times higher than that expected). Demography:
      mean age: 6.9 years (5.7 SDU); age group 0-5 years age: 56.7 %; females: 51.3 %.
      No significant demographic differences were observed in gypsy children compared
      with the general population of maltreated children. However, factors that were
      significantly more frequent in gypsy children were the prevalence of passive
      maltreatment (p = 0.0133; odds ratio [OR]: 2.4; 95 % confidence interval [CI]:
      1.2-4.9), belonging to families with more than one social and health risk factor
      (p = 0.0000; OR: 30.5; 95 % CI: 9.4-99.1) with problems of delinquency (p =
      0.0000; OR: 11.7; 95 % CI: 6.3-21.7) and with a history drug/alcohol abuse (p =
      0.0000; OR: 3.4; 95 % CI: 1.9-6), presenting at least one health problem (p =
      0.0000; OR: 6.9; 95 % CI: 2.7-17.3), absent or incomplete immunizations (p =
      0.0000; OR: 4.9; 95 % CI: 3-8.1), disabilities (p = 0.0012; OR: 2.9; 95 % CI: 1.5
      5.9) especially of neurological origin (p = 0.0000; OR: 4.8; 95 % CI: 2-11.4),
      psychomotor developmental delay in children younger than 6 years (p = 0.0330; OR:
      2.4; 95 % CI: 1-5.3) and behavioral disorders in adolescents (p = 0.0005; OR:
      4.7; 95 % CI: 1.8-12.1). CONCLUSIONS: There is a significant association between
      maltreatment of gypsy children and the presence in their family of social and
      health risk factors such as delinquency and mental health problems related to
      drug addiction/alcoholism. The health status of these children is significantly
      different from that observed in maltreated children from the general population,
      with a greater incidence of neurological disabilities and problems and diseases
      related to chronic neglect and/or abandonment of the child's health, socio
      educational and psycho-emotional needs. These children are admitted to centers of
      protection more frequently than their theoretical risk would predict.

PMID- 14718128
TI  - [Tuberculous infection from an area of high incidence of tuberculosis and with a
      high proportion of immigrants].
AB  - BACKGROUND: Historically the district of Ciutat Vella in Barcelona has a high
      incidence of tuberculosis (TB) and, more recently, it is home to a considerable
      proportion of immigrants. OBJECTIVES: To determine the prevalence of tuberculous
      infection (TI) in a pediatric population from this district and evaluate the
      impact of immigration. METHODS: Children and adolescents aged < 16 years old were
      screened using the tuberculin skin test (TST) mainly in visits of the healthy
      child program. Proportions were compared using the x2 test and adjusted odds
      ratios were estimated through a logistic regression model. RESULTS: Six hundred
      ninety-nine children were studied. The overall prevalence of positive TST was 3.4
      % (95 % CI: 2.2 %-5.1 %). Prevalence increased with age (P 5 0.009) from 1.9 % in
      children aged 1-5 years old to 6.4 % in children and adolescents aged 10-15
      years. A total of 88.3 % of the immigrants had been vaccinated with BCG compared
      with 2.5 % of autochthonous children and adolescents (P < 0.001). The prevalence
      ratio between immigrants and autochthonous children was 2.1 (P 5 0.07). Three
      cases of TB disease were detected among children, but no index case was found in
      children with TI. CONCLUSIONS: The high TI prevalence found suggest that living
      in the district is a risk factor, which justifies routine TST screening of all
      the children living there. The present criteria for the interpretation of TST in
      immigrants vaccinated with BCG residing in areas of high incidence are dubious.

PMID- 14718130
TI  - [Foreign minors in the protection system of the Autonomous Community of Aragon
      (Spain)].
AB  - OBJECTIVES: To determine the prevalence of foreign minors in protection centers,
      their demographic characteristics, and reasons for entry, as well as the relation
      with geographic area, family, social and health risk factors, and high-priority
      health needs. PATIENTS AND METHODS: We performed a retrospective cross-sectional
      study over an 11-year period (1992-2002). The health and socio-familial reports
      of 1,619 minors who were admitted to protection centers were reviewed and those
      from a foreign country were included. Compilation of information, definition of
      concepts, and health assessments were performed according to standard protocols.
      RESULTS: Two hundred forty-one foreign minors (males 66.4 %) with a mean age (SD)
      of 11 (3.2) years (adolescents 64.7 %, infants-preschoolers 26.1 %) were admitted
      during the study period. The prevalence was 4.6 times higher than that expected.
      Origin: Africa 68.9 % (Maghreb 56.4 %, sub-Saharan 12.5 %), Europe 23.6 % (west
      14.5 %, east 9.1 %), Latin-America 5.4 %, and Asia 2.1 %. Reasons for entry,
      demography and relation with geographic area were as follows: 1. Being an
      abandoned illegal immigrant 41.1 % (all male adolescents, 98 % from the Maghreb);
      2. Maltreatment 33.2 % (passive maltreatment-to-active ratio 2.3:1, no difference
      by sex, age mode 2 years; Asia 80 %; Europe 61.5 %, west-to-east ratio 4.8:1,
      gypsy ethnicity from Portugal and Rumania 90.3 %; Latin-America 38.4 %; Africa
      21.7 %, no difference by geographic area); 3. Temporary incapacity for their care
      18.7 % (female-to-male ratio 1.8:1, age mode 1 year; Latin-America 38.4 %, Africa
      18.1 %, Europe 17.5 %); 4. Other causes 7 %. RISK FACTORS: at least one (78.4 %)
      and more than one (33.6 %); housing problems and especially living in a single
      parent family. Health disorders: at least one (65.1 %); disabling disease (2.1
      %); main problems: dental (36.3 %), immunization (27.6 %), dermatologic (19.1 %),
      growth and nutrition (13.7 %), and infectious and parasitic diseases (13.3 %).
      CONCLUSIONS: Being a minor immigrant in a foreign country with problems of
      documentation, housing or family regrouping and especially if there are language,
      cultural or racial (ethnic minorities) barriers is a major risk factor for living
      in a situation of vulnerability, risk or neglect/abandonment that requires social
      protection measures. Continuous follow-up by the social services of the adoptive
      community is required for the prevention and early detection of children in need
      of protection.

PMID- 14718131
TI  - [Pediatric liver transplantation. Indications, surgical techniques, complications
      and treatment].

PMID- 14718132
TI  - [Levels of care and minimum recommendations for neonatal healthcare].

PMID- 14718133
TI  - [Recommendations in neonatal resuscitation].
AB  - The recommendations for neonatal resuscitation are not always based on sufficient
      scientific evidence and thus expert consensus based on current research,
      knowledge, and experience are useful for formulating practical protocols that are
      easy to follow. The latest recommendations, in 2000, modified previously
      published recommendations and are included in the present text.

PMID- 14718134
TI  - [Group B Streptococcus late-onset disease presenting as cellulitis-adenitis
      syndrome].
AB  - Cellulitis-adenitis syndrome is a rare clinical manifestation of group B
      Streptococcus (GBS) late-onset disease. Its significance lies in the fact that
      local infection may be the only initial sign of systemic infection that is often
      concurrent with meningitis. Soft tissue involvement (cellulitis-adenitis) can
      sometimes be the only initial manifestation of GBS infection. We report four
      cases of GBS cellulitis-adenitis syndrome from different hospitals in Barcelona
      and Tarragona. We emphasize that early diagnosis and treatment may improve the
      potentially poor prognosis of these patients, and stress the need to rule out
      central nervous system involvement by studying cerebrospinal fluid.

PMID- 14718135
TI  - [De novo partial duplication of the distal segment of the long arm of chromosome
      5 (q31--> qter). Report of a new case].
AB  - We report a case of de novo partial duplication of the distal segment of the long
      arm of chromosome 5 (q31--> qter). The patient showed dysmorphic features (flat
      face, short and horizontal palpebral fissures, depressed and broad nasal bridge,
      wide nose with hypoplastic alae nasae, short and flat philtrum, high arched
      palate, micrognathia, anomalies of the ears), redundant adipose panniculus of the
      neck, proximal shortening of the limbs, flexion contractures, long and distally
      widened fingers, bilateral clubfoot, single umbilical artery, hypoplasia of lung
      and pulmonary arteries, atrial septal defect and patent ductus arteriosus. She
      died 23 hours after birth from respiratory failure. Chromosome analysis with high
      resolution GTG bands showed 46,XX,1p1, which was interpreted as a partial
      duplication of the distal long arm of chromosome 5 (q31--> qter). Fluorescence in
      situ hybridization analyses with whole chromosome painting technique for
      chromosome 5 proved that this extra region belonged to chromosome 5. Our case is
      the first to have a de novo partial duplication of this chromosome segment.

PMID- 14718136
TI  - [Recurrent parotiditis].

PMID- 14718137
TI  - [Palivizumab prophylaxis against respiratory syncytial virus. Should its
      indications be reviewed?].

PMID- 14718138
TI  - [One-year experience of the breast feeding forum for professionals and parents].

PMID- 14718139
TI  - [Multiple juvenile xanthogranuloma: a diagnosis to be considered in primary
      care].

PMID- 14718140
TI  - [Holt-Oram syndrome].

PMID- 14718141
TI  - [Unilateral type 1 segmental Darier disease].

PMID- 14718142
TI  - [Hypertrophic cardiomyopathy and neurofibromatosis type 1].

PMID- 14718144
TI  - [Sentinel lymph node (SN) detection in patients with breast cancer. Influence of
      tumor size and age of the patient].
AB  - OBJECTIVE: The objective of this study is to analyze the influence of tumor size
      and age of the patient in the detection of the SN in breast neoplasms. MATERIAL
      AND METHODS: A total of 190 patients affected of breast cancer with a mean age of
      57 years (range from 28 to 87 years) were studied. According to age, the
      following were distinguished: under 40 years, 23 patients; between 40 and 60
      years, 102 patients and over 60 years, 65 patients. The lesions were classified
      based on size (in mm) into: less than 10 in 27 patients, between 10 and 20 in 61
      patients, between 20 and 30 in 64 patients, and greater than 30 in 38 patients.
      In all the cases, a scintigraphy was performed at 2 hr. post-injection of 3 mCi
      of 99mTc-nanocoloide, in the peritumoral area. After lymphoscintigraphy detection
      of the SN, cutaneous labeling was performed and it was detected surgically by a
      gamma detector probe. A complete lymphadenectomy was performed in all the
      patients. The histopathology was performed with hematoxylin-eosin and
      immunohistochemistry techniques and the state of the SN was compared with the
      remaining lymph nodes of the lymphadenectomy. RESULTS: The SN was located in 169
      of the 190 cases (89%). In 164 cases, it was found in the axilla. The greatest
      percentage of those not detected was observed in tumors over 30 mm (32%) and
      patients older than 60 years (30%). No false negative were observed in tumors
      under 10 mm or in patients under 40 years, but the false negative rate increased
      with the patient's age and the tumor size. CONCLUSIONS: The patient's age and
      tumor size seem to influence SN detection rates. The FN rates seem to be superior
      in patients over 60 years. Patients under 40 years with tumors less than 10 mm
      are those who benefit most from this technique.

PMID- 14718145
TI  - [Study of the sentinel node in breast cancer using lymphoscintigraphy and a fast
      method for cytokeratin].
AB  - INTRODUCTION: Histopathological examination of the axillary sentinel node (SN) is
      becoming a routine procedure in the surgical phase of infiltrating ductal
      carcinoma of the breast (IDC). The SN exam may yield false negative cases mainly
      due to identification failure of the SN but some of the false negative cases may
      be the result of the pathological examination procedure applied. MATERIAL AND
      METHODS: Sixty two (62) cases of clinically staged N0 IDC of the breast by TNM
      nomenclature were assigned to breast surgery along with conventional axillary
      node dissection. The identification technique included lymphoscintigraphy and
      intraoperative gamma-detecting probe after peritumoral injection of 99mTc-labeled
      colloids.The histological study of SN was performed with paired 4 microm slices
      and staining with hematoxylin-eosin and with a fast method of cytokeratins for
      freezing. RESULTS: In only two of the 62 patients, it was not possible to
      identify the SN. Eighteen of the remaining 60 had SN involvement by metastasis,
      having no metastases in the other nodes of the axillary dissection in 6 of them.
      Ten of those were micrometastasis (size of metastasis= or <0.2 cm). In two out of
      these last 10 cases, diagnosis of the micrometastasis was only possible using
      slices stained with CK. There were no false negative results. CONCLUSIONS: The
      lymphoscintigraphy, after peritumoral injection of small volumes and low dose of
      the tracer, makes it possible to obtain excellent results in the intraoperative
      detection of the SN in breast cancer. The study of this SN with a fast method for
      CK decreases the number of false negative results of the technique.

PMID- 14718146
TI  - [Characterization of the difference between filtered back projection and ordered
      subsets expectation maximization in spect images using the Wavelet Transform].
AB  - Efficiency of reconstruction algorithms is important to guarantee quality of
      Nuclear Medicine tomographic images. The algorithms belong to one of two types:
      analytical or statistical. The Filtered Back Projection (BP) algorithm belongs to
      the first group and the Ordered Subsets Expectation Maximization (OSEM) algorithm
      belongs to the second group. The aim of the present paper was to compare both
      algorithms by means of the Wavelet Transform (WT). This tool was selected because
      of its capability to divide the image into different frequency levels without
      losing information about their spatial position. The WT was applied on the Haar
      basis without decimation in order to compare matrixes of the same size. Attention
      was drawn to the relative presence of three typical perturbations: Poisson noise,
      annular artifacts that express a deficient correction to the planar uniformity
      and attenuation phenomenon. With these purposes, we studied homologue transversal
      slices of images of homogeneous distribution of activity. The OSEM algorithm not
      only greatly improves the filtering of the Poisson noise, but also diminishes the
      annular artifacts, mainly at the image zone that coincides with the rotation
      center. The intensity of the attenuation phenomenon was the same with both
      algorithms, except in the peripheral zone where OSEM showed a slightly higher
      activity than BP. These observations encourage our interest to continue applying
      the WT not only to identify the artifacts, but also to try to decrease their
      deleterious influence on Nuclear Medicine images.

PMID- 14718147
TI  - [Labeling of leukocytes using stannous 99mTc-colloid in whole blood samples].
AB  - This paper presents the preparation of a radiocolloid that still makes it
      possible to label leukocytes using its phagocytosis capacity. Given that this
      function is exclusively of the white blood cells, not being exercised by other
      blood cells, the use of a stannous fluoride radiocolloid labeled with 99mTc (F2Sn
      99mTc) was tested in order to label leukocytes in whole blood samples. Using
      cellular separation techniques in density gradients and acquisition of images in
      gamma camera of radioactivity distribution in Percol, it was observed that the
      white cells labeling achieved was selective and with high efficiency for
      leukocytes (in all cases, it was superior to 70%), optimal reproducibility, low
      cost and low cellular toxicity.

PMID- 14718148
TI  - [Use of Gated-SPECT with with 99mTC-MIBI in the evaluation of the prognostic
      significance of ventricular arrhythmias during a stress test].
AB  - The presence of ventricular complex cardiac arrhythmias in coronary patients,
      both at rest or during physical exercise, is considered a risk factor for future
      coronary events or sudden death during long time follow up. The meaning of
      ventricular complex arrhythmias (VCA) in patients with normal ventricular
      function and without myocardium ischemia has still not been explained. This study
      aimed to evaluate if patients with normal ventricular function and no evidence of
      cardiac ischemia (determined by means of Gated SPECT) who developed VCA during
      stress test show an increase in cardiac events on later monitoring. PATIENTS AND
      METHODS: All patients were studied by means of an ergometric exercise test using
      a standard Bruce protocol and Gated SPECT with Methoxyisobutyl Isonitrile
      99mTechnetium (99mTC-MIBI). Sixty-seven (67) patients with normal ventricular
      function and no evidence of cardiac ischemia were included. RESULTS: 13 patients
      had VCA and 54 had no ventricular arrhythmias during stress test. During the
      follow up of 681.3 +/- 469 days, none of the 13 patients had sudden death, angina
      pectoris or myocardium infarction. CONCLUSIONS: In our sample, the appearance of
      VCA during stress test in patients without myocardium ischemia and normal
      ventricular function was not associated with an increase of cardiac events during
      the monitoring which was carried out.

PMID- 14718149
TI  - [Diabetes mellitus and pancreatic tumor].
AB  - A 68 year old Ecuadorian man was investigated for polyuria, polydipsia and weight
      loss of 3 kg during the previous two months. Insulin dependent diabetes mellitus
      was diagnosed 10 year before admission and treated with appropriate diet and
      insulin (35 U/d). 18 months before was diagnosed in El Ecuador of "multiple liver
      nodes non-suggestive of malignancy". Physical examination showed a large
      multinodular petrous hepatomegaly. There was no evidence of skin lesions. Results
      of laboratory studies included a basal plasma glucose level that ranged between
      275-367 mg/dl (N=60-100), glycosylated haemoglobin of 8.9% (N<5) and a serum
      albumin of 2.8 gr./dl (N=3.4-4.8). At admission non-other laboratory alterations
      were detected. Computed tomography showed a mass on the head of the pancreas with
      loco-regional lymph nodes and liver metastases. Tumor markers were normal. Fine
      needle aspiration cytology of the liver masses revealed the presence of liver
      metastases of a non-differentiated malignant tumor. A 111In-DTPAOC scintigraphy
      revealed the presence of somatostatin receptors in the liver metastases, also
      detecting the presence of multiple bone metastases in the axial and appendicular
      skeleton. Plasma glucagon level was 678 pg/ml (N<250). A diagnosis of metastatic
      glucagonoma was established and therapy with streptozocin, 5-FU, insulin and
      synthetic somatostatin analogs was initiated. Three months after the therapy
      initiation the patient was symptom free. Some weeks after the patient suffered
      from left hip pain, and a control 111In-DTPA scintigraphy showed progression of
      his bone metastases. In conclusion, glucagonoma must be suspected in all diabetic
      patients with metastatic liver, even in absence of necrotic migratory erythema.
      In these circumstances, plasmatic glucagon level and somatostatin receptors
      scintigraphy will be a useful tool for establishing the final diagnosis.

PMID- 14718150
TI  - [Confirmation of cortical lesions of progressive prosopagnosia by cerebral
      SPECT].
AB  - We present the case of a 78 year old man admitted to the hospital with
      progressive memory disorder. Neuropsychological examination showed inability to
      recognize familiar faces (prosopagnosia). MRI documented cortical atrophy, which
      did not explain the neurological deficit. CT did not show abnormalities. Most
      patients with prosopagnosia present brain atrophy, as they are more than 65 years
      old. Scanning by SPECT revealed hypoperfusion in the right parietotemporal
      region, which was worse in a later examination.

PMID- 14718151
TI  - [Peritoneal scintigraphy in patients with dialysis].

PMID- 14718152
TI  - [Intraosseous lipomatosis: positivity in bone scintigraphy with 99mTc-HDP].

PMID- 14718153
TI  - [Interposition of the colonic loops simulating a hepatic space occupying lesion
      in scintigraphy with 99mTc-HMPAO leukocytes].

PMID- 14718154
TI  - [Cytosolic CA125 in lung squamous cell carcinomas].

PMID- 14718155
TI  - [Radioisotopic synoviorthesis].

PMID- 14718157
TI  - A new year and a new era for cell.

PMID- 14718158
TI  - Initiation of DNA replication: a new hint from archaea.
AB  - In this issue, Robinson and coworkers provide new insights into the mechanisms of
      initiation of chromosome replication in Archea. This and other studies, focused
      on model organisms, will certainly help to understand how the replication process
      has evolved in Eukaryotes.

PMID- 14718159
TI  - A common switch used by plants and animals.
AB  - Comparisons of plant and animal development usually highlight their differences.
      The discovery that a kinase of the MAPKK class plays a key role in cell
      specification at the first division of the Arabidopsis embryo suggests that there
      may be similarities based on a common logic.

PMID- 14718160
TI  - Old drugs, new tricks: using genetically sensitized yeast to reveal drug targets.
AB  - A study in this issue of Cell illustrates the power of applying genomic
      approaches with model systems to characterize the biological activity of small
      molecules and to identify their cellular targets, which can clarify the mode of
      action of human therapeutics.

PMID- 14718163
TI  - Metal import through microbial membranes.
AB  - Transport systems of Gram-negative bacteria coordinate the passage of metabolites
      through the outer membrane, periplasm, and the cytoplasmic membrane without
      compromising the protective properties of the cell envelope. Active transporters
      orchestrate the import of metals against concentration gradients. These
      thermodynamically unfavorable processes are coupled to both an electrochemical
      proton gradient and the hydrolysis of ATP. Crystallographic structures of
      transport proteins now define in molecular detail most components of an active
      metal import pathway from Escherichia coli.

PMID- 14718164
TI  - Identification of two origins of replication in the single chromosome of the
      archaeon Sulfolobus solfataricus.
AB  - Eukaryotic chromosomes possess multiple origins of replication, whereas bacterial
      chromosomes are replicated from a single origin. The archaeon Pyrococcus abyssi
      also appears to have a single origin, suggesting a common rule for prokaryotes.
      However, in the current work, we describe the identification of two active
      origins of replication in the single chromosome of the hyperthermophilic archaeon
      Sulfolobus solfataricus. Further, we identify conserved sequence motifs within
      the origins that are recognized by a family of three Sulfolobus proteins that are
      homologous to the eukaryotic initiator proteins Orc1 and Cdc6. We demonstrate
      that the two origins are recognized by distinct subsets of these Orc1/Cdc6
      homologs. These data, in conjunction with an analysis of the levels of the three
      Orc1/Cdc6 proteins in different growth phases and cell cycle stages, lead us to
      propose a model for the roles for these proteins in modulating origin activity.

PMID- 14718165
TI  - Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in
      DNA replication and repair.
AB  - Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell
      nuclear antigen (PCNA) are central to DNA replication and repair. To clarify the
      molecular basis of FEN-1 specificity and PCNA activation, we report here
      structures of FEN-1:DNA and PCNA:FEN-1-peptide complexes, along with fluorescence
      resonance energy transfer (FRET) and mutational results. FEN-1 binds the unpaired
      3' DNA end (3' flap), opens and kinks the DNA, and promotes conformational
      closing of a flexible helical clamp to facilitate 5' cleavage specificity.
      Ordering of unstructured C-terminal regions in FEN-1 and PCNA creates an
      intermolecular beta sheet interface that directly links adjacent PCNA and DNA
      binding regions of FEN-1 and suggests how PCNA stimulates FEN-1 activity. The DNA
      and protein conformational changes, composite complex structures, FRET, and
      mutational results support enzyme-PCNA alignments and a kinked DNA pivot point
      that appear suitable to coordinate rotary handoffs of kinked DNA intermediates
      among enzymes localized by the three PCNA binding sites.

PMID- 14718166
TI  - Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or
      independent of DNA synthesis.
AB  - Deposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA
      replication and possibly DNA repair, whereas histone variant H3.3 serves as the
      replacement variant for the DNA-synthesis-independent deposition pathway. To
      address how histones H3.1 and H3.3 are deposited into chromatin through distinct
      pathways, we have purified deposition machineries for these histones. The H3.1
      and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we
      show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome
      assembly, respectively. Notably, these complexes possess one molecule each of
      H3.1/H3.3 and H4, suggesting that histones H3 and H4 exist as dimeric units that
      are important intermediates in nucleosome formation. This finding provides new
      insights into possible mechanisms for maintenance of epigenetic information after
      chromatin duplication.

PMID- 14718167
TI  - Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1.
AB  - The molecular mechanism underlying the retention of intron-containing mRNAs in
      the nucleus is not understood. Here, we show that retention of intron-containing
      mRNAs in yeast is mediated by perinuclearly located Mlp1. Deletion of MLP1
      impairs retention while having no effect on mRNA splicing. The Mlp1-dependent
      leakage of intron-containing RNAs is increased in presence of ts-prp18 delta, a
      splicing mutant. When overall pre-mRNA levels are increased by deletion of RRP6,
      a nuclear exosome component, MLP1 deletion augments leakage of only the intron
      containing portion of mRNAs. Our data suggest, moreover, that Mlp1-dependent
      retention is mediated via the 5' splice site. Intriguingly, we found Mlp-proteins
      to be present only on sections of the NE adjacent to chromatin. We propose that
      at this confined site the perinuclear Mlp1 implements a quality control step
      prior to export, physically retaining faulty pre-mRNAs.

PMID- 14718168
TI  - Sus1, a functional component of the SAGA histone acetylase complex and the
      nuclear pore-associated mRNA export machinery.
AB  - Gene expression is a coordinated multistep process that begins with transcription
      and RNA processing in the nucleus followed by mRNA export to the cytoplasm for
      translation. Here we report the identification of a protein, Sus1, which
      functions in both transcription and mRNA export. Sus1 is a nuclear protein with a
      concentration at the nuclear pores. Biochemical analyses show that Sus1 interacts
      with SAGA, a large intranuclear histone acetylase complex involved in
      transcription initiation, and with the Sac3-Thp1 complex, which functions in mRNA
      export with specific nuclear pore proteins at the nuclear basket. DNA macroarray
      analysis revealed that Sus1 is required for transcription regulation. Moreover,
      chromatin immunoprecipitation showed that Sus1 is associated with the promoter of
      a SAGA-dependent gene during transcription activation. Finally, mRNA export is
      impaired in sus1 mutants. These data provide an unexpected connection between the
      SAGA histone acetylase complex and the mRNA export machinery.

PMID- 14718169
TI  - The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone
      p50(cdc37).
AB  - Recruitment of protein kinase clients to the Hsp90 chaperone involves the
      cochaperone p50(cdc37) acting as a scaffold, binding protein kinases via its N
      terminal domain and Hsp90 via its C-terminal region. p50(cdc37) also has a
      regulatory activity, arresting Hsp90's ATPase cycle during client-protein
      loading. We have localized the binding site for p50(cdc37) to the N-terminal
      nucleotide binding domain of Hsp90 and determined the crystal structure of the
      Hsp90-p50(cdc37) core complex. Dimeric p50(cdc37) binds to surfaces of the Hsp90
      N-domain implicated in ATP-dependent N-terminal dimerization and association with
      the middle segment of the chaperone. This interaction fixes the lid segment in an
      open conformation, inserts an arginine side chain into the ATP binding pocket to
      disable catalysis, and prevents trans-activating interaction of the N domains.

PMID- 14718170
TI  - Golgi membranes remain segregated from the endoplasmic reticulum during mitosis
      in mammalian cells.
AB  - What happens to organelles during mitosis, and how they are apportioned to each
      of the daughter cells, is not completely clear. We have devised a procedure to
      address whether Golgi membranes fuse with the Endoplasmic Reticulum (ER) during
      mitosis via the detection of interactions between ER and Golgi proteins. This
      procedure involves coexpressing an FKBP-tagged Golgi enzyme with an ER-retained
      protein fused to FRAP in COS cells. Since treatment with rapamycin induces a
      tight association between FKBP and FRAP, one would expect rapamycin to trap the
      FKBP-fused Golgi protein in the ER if it ever visits the ER during mitosis.
      However, after the doubly transfected cells progress through mitosis in the
      presence of rapamycin, we find the Golgi protein in the newly formed Golgi stacks
      and not in the ER. Based on these results, we conclude that Golgi membranes
      remain separate from the ER during mitosis in mammalian cells.

PMID- 14718171
TI  - A MAPKK kinase gene regulates extra-embryonic cell fate in Arabidopsis.
AB  - The Arabidopsis zygote divides asymmetrically into an embryonic apical cell and a
      basal cell with mostly extra-embryonic fate. This fundamental asymmetry sets the
      stage for further embryonic development, but the events mediating it are poorly
      understood. We have identified a MAPKK kinase gene, named YODA, that promotes
      extra-embryonic cell fates in the basal lineage. In loss-of-function mutants, the
      zygote does not elongate properly, and the cells of the basal lineage are
      eventually incorporated into the embryo instead of differentiating the extra
      embryonic suspensor. Gain-of-function alleles cause exaggerated growth of the
      suspensor and can suppress embryonic development to a degree where no
      recognizable proembryo is formed. Our results imply that a MAP kinase cascade
      acts as a molecular switch promoting extra-embryonic fate.

PMID- 14718172
TI  - Discovering modes of action for therapeutic compounds using a genome-wide screen
      of yeast heterozygotes.
AB  - Modern medicine faces the challenge of developing safer and more effective
      therapies to treat human diseases. Many drugs currently in use were discovered
      without knowledge of their underlying molecular mechanisms. Understanding their
      biological targets and modes of action will be essential to design improved
      second-generation compounds. Here, we describe the use of a genome-wide pool of
      tagged heterozygotes to assess the cellular effects of 78 compounds in
      Saccharomyces cerevisiae. Specifically, lanosterol synthase in the sterol
      biosynthetic pathway was identified as a target of the antianginal drug
      molsidomine, which may explain its cholesterol-lowering effects. Further, the
      rRNA processing exosome was identified as a potential target of the cell growth
      inhibitor 5-fluorouracil. This genome-wide screen validated previously
      characterized targets or helped identify potentially new modes of action for over
      half of the compounds tested, providing proof of this principle for analyzing the
      modes of action of clinically relevant compounds.

PMID- 14718174
TI  - MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone], a drinking-water
      carcinogen, does not induce mutations in the liver of cII transgenic medaka
      (Oryzias latipes).
AB  - Mutagenicity assays with Salmonella have shown that 3-chloro-4-(dichloromethyl)-5
      hydroxy-2[5H]-furanone (MX), a drinking-water disinfection by-product, is a
      potent mutagen, accounting for about one-third of the mutagenic potency/potential
      of chlorinated drinking water. The ability of MX to induce mutations was
      investigated in the liver of medaka (Oryzias latipes), a small fish model,
      utilizing the cII transgenic medaka strain that allows detection of in vivo
      mutations. Methylazoxymethanol acetate (MAMAc), a carcinogen in medaka, served as
      a positive control. Fish were exposed to MX at 0, 1, 10, or 30 mg/L for 96 h,
      whereas the MAMAc exposures were for 2 h at 0, 0.1, 1, or 10 mg/L. Both exposures
      were conducted under static water conditions and with fasted medaka. Following
      exposure, fish were returned to regular culture conditions to allow mutation
      expression for 15 or 40 d for MX or for 15 or 32 d for MAMAc. Mutations were not
      induced in medaka exposed to MX for 96 h. However, a concentration- and time
      dependent increase in mutations was observed from the livers of fish exposed to 1
      and 10 mg/L MAMAc. In conclusion, mutation induction was not observed in the
      livers of cII medaka exposed to MX for 96 h; however, studies are planned to
      examine mutation induction in the gills and skin to explore the possibility that
      MX-induced DNA damage occurs primarily in the tissues of initial contact.

PMID- 14718175
TI  - Effects of perinatal simultaneous exposure to tributyltin (TBT) and p,p'-DDE [1,1
      dichloro-2,2-bis(p-chlorophenyl) ethylene) on male offspring of Wistar rats.
AB  - p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; DDE] and tributyltin
      (TBT) are ubiquitous in the environment and in Japan were shown to bioaccumulate
      in marine products. Thus these chemicals serve as a source of contaminant in the
      mammalian food chain. Fetuses and neonates through maternal ingestion may be
      exposed to DDE and TBT. Therefore, the effects of concurrent exposure to DDE and
      TBT were investigated in male Wistar rat offspring of dams ingesting these two
      contaminants. In this study, TBT suppressed the growth and delayed eye opening.
      However, both growth retardation and delayed eye opening produced by TBT failed
      to occur in the presence of DDE. Unexpectedly, the prostate weight of male rat
      offspring was significantly reduced with the administration of TBT but restored
      in the presence of DDE. These results indicate that TBT and DDE affected the
      development of male rat offspring following maternal exposure, and simultaneous
      administration of DDE prevented some of the observed effects of TBT, especially
      of an antagonistic nature, through a mechanism, still to be determined.

PMID- 14718176
TI  - Accumulation of dietary cadmium (Cd) in rabbit tissues and excretions: a
      comparison of lettuce amended with soluble Cd salt and lettuce with plant
      incorporated Cd.
AB  - Quantifying the transfer of Cd from foods to mammalian target organs is key to
      estimating the health risk from this exposure; however, the bioaccumulation of Cd
      from foods is modified by many dietary components. Studies of dietary Cd
      absorption would be simpler if it were known that Cd added to foods as a soluble
      salt was as bioavailable as Cd incorporated during growth of the food species.
      Rabbits were fed, for 16 d, fresh lettuce containing cadmium incorporated into
      the lettuce during growth or added to the lettuce before feeding, or lettuce with
      no Cd but soluble Cd administered to the animals by gavage. There was a marked
      positive relationship between increased Cd dose and its accumulation in kidney;
      the slopes for the gavage and added treatments were not clearly different from
      the incorporated treatment; liver data were highly variable. In a 10-wk study of
      Cd-incorporated and -amended lettuce diets, for the incorporated and control
      diets there was less Cd accumulation in the kidneys, but not liver, per unit
      cumulative dose, than for the amended diet. Cd accumulation in the small
      intestine and Cd concentration in feces, both per unit daily dose, were smaller
      for the incorporated than for the control and amended diets; Cd concentrations in
      bile, urine, and serum, per unit daily dose, were higher in the control diet than
      values in the amended diet, which were higher than the incorporated diet. These
      differences could not be accounted for by variation in Fe or Zn contents of the
      diets. Thus, data suggest that Cd-amended diets overestimate bioaccumulation in
      kidney, an important target organ, by up to one-third, and that studies of short
      duration are not adequate to evaluate Cd bioavailability from food.

PMID- 14718177
TI  - Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C
      to prevent the damage.
AB  - The effects of hyperthyroidism on oxidative DNA damage in liver tissue and
      modification by vitamin C supplementation were investigated in rats. Animals were
      rendered hyperthyroid by administration of L-thyroxine (0.4 mg/100 g food) for 25
      d. In the plasma samples, T(3), T(4), and thyroid-stimulating hormone (TSH) were
      measured by radioimmunoassay and ascorbate spectrophotometrically. Oxidative
      damage to hepatic nuclear DNA was determined by measuring deoxy-guanosine (dG)
      and 8-oxodG by high-performance liquid chromatography with diode array detector
      electrochemical detection (HPLC-DAD-ECD). In hyperthyroidism, 8-oxodG/(10(5) dG)
      levels were significantly higher and plasma vitamin C levels lower than in
      control rats. The results of this experimental study show that oxidative damage
      to hepatic nuclear DNA increases in the hyperthyroid state and that vitamin C was
      not effective in preventing this damage.

PMID- 14718178
TI  - Kinetic factors involved in the metabolism of benzene in mouse lung and liver.
AB  - Benzene is an occupational and environmental toxicant. The main human health
      concern associated with benzene exposure is acute myelogenous leukemia. Benzene
      produces lung tumors in mice, while its effects on human lung are not clear. The
      adverse effects of benzene are dependent on its metabolism by the cytochrome P
      450 enzyme system. The isozymes CYP2E1 and CYP2F2 play roles in the metabolism of
      benzene at low, environmentally relevant concentrations. Previous studies
      indicate that the mouse lung readily metabolizes benzene and that CYP2F2 plays a
      role in this biotransformation. The significance of CYP2E1 and CYP2F2 in benzene
      metabolism was determined by measuring their apparent kinetic parameters K(m) and
      V(max). Use of wild-type and CYP2E1 knockout mice and selective inhibitors
      allowed the determination of the individual importance of both CYP2E1 and CYP2F2
      in mouse liver and lung. A simple Michaelis-Menten relationship involving
      Lineweaver-Burk plots for the microsomal metabolism of benzene shows the apparent
      kinetic factors are different between the wild-type (K(m): 30.4 microM, V(max):
      25.3 pmol/mg protein/min) and knockout (K(m): 1.9 microM, V(max): 0.5 pmol/mg
      protein/min) mouse livers. Wild-type lung has a K(m) of 2.3 microM and V(max) of
      0.9 pmol/mg protein/min. CYP2E1 knockout lung has similar affinity and metabolic
      activity with a K(m) of 3.7 microM and V(max) of 1.2 pmol/mg protein/min. These
      data suggest CYP2E1 is less important in the lung than liver, and that it has a
      lower affinity for benzene but higher rate of hydroxylated metabolite production
      than does CYP2F2, which plays the predominant role in metabolizing benzene in
      mouse lung.

PMID- 14718179
TI  - Neurologic and immunologic effects of exposure to corticosterone, chlorpyrifos,
      and multiple doses of tri-ortho-tolyl phosphate over a 28-day period in rats.
AB  - An animal (rat) model of chronic stress (corticosterone in the drinking water)
      was used to study the interaction of stress and the organophosphorus (OP)
      neurotoxicants chlorpyrifos (60 mg/kg subcutaneously in a single dose) and tri
      ortho-tolyl phosphate (TOTP, at 75, 150, or 300 mg/kg given 7 times orally in a 2
      wk period). Adult male Long-Evans rats were provided with corticosterone in
      drinking water (400 microg/ml, w/v) for a total of 28 d, which led to
      significantly decreased weight and decreased cellularity of the thymus and
      spleen. Seven days after initiation of corticosterone treatment, half of the rats
      were given chlorpyrifos, and an additional 7 d later the 2-wk, 7-dose treatment
      of TOTP was initiated. During the 28-d test period, behavior of rats was
      evaluated using a functional observational battery (FOB), motor activity, and
      passive avoidance. Reductions in body weight, grip strength, and ambulatory
      movements occurred as a result of corticosterone treatment. Decreased body weight
      and grip strength were also elicited by TOTP, and the interactions of
      corticosterone and TOTP enhanced the effects on body weight and grip strength.
      Blood cholinesterase levels were obtained during the 28-d study period and found
      useful for monitoring OP exposure. At the end of the 28-d testing period, rats
      were sacrificed and activities of cholinesterase, neurotoxic esterase (neuropathy
      target esterase), and/or carboxylesterase were evaluated in blood, liver, and/or
      brain regions (basal forebrain, caudate putamen, cerebral cortex, hippocampus).
      All these esterases in brain were inhibited in a dose-related manner by TOTP,
      with some enhancement in rats drinking corticosterone-containing water. In
      addition, choline acetyltransferase, glial acidic fibrillary protein (GFAP),
      glutathione peroxidase, and superoxide dismutase were evaluated in one or more of
      the brain regions already identified. Choline acetyltransferase, glutathione
      peroxidase, and superoxide dismutase activities were unaffected by treatments.
      However, GFAP was elevated above control levels in the cerebral cortex of rats by
      all treatments (corticosterone, chlorpyrifos, TOTP). Neuropathological
      examination revealed early stages of dose-related increased distal myelinated
      fiber axonal degeneration seen in the medullary fasciculus gracilis at only the
      highest dose of TOTP (300 mg/kg).

PMID- 14718181
TI  - Encapsulation of PROLI/NO in biodegradable microparticles.
AB  - Biodegradable hydrophilic polymers poly-lactic-co-glycolic acid (PLGA) and
      polyethylene oxide-co-lactic acid (PELA) were used to encapsulate a small
      hydrophilic prodrug (PROLI/NO) as a strategy to deliver nitric oxide (NO) by
      inhalation. The microparticles were prepared using double emulsion and solvent
      evaporation, followed by freeze-drying. The NO release kinetics were
      characterized by three parameters: the maximum concentration of NO per unit
      weight of microparticles, C(max) (nM mg(-1)); the window of time for which the
      concentration exceeded 50% of C(max), W(50) (min); and the initial rate of
      release, R(i) (nM mg(-1) min(-1)). PLGA-based microparticles did not encapsulate
      PROLI/NO. PELA-based microparticles demonstrated an entrapment efficiency rate of
      43%, a mass median diameter of 2.3 micro m, and NO release in a physiological
      buffer characterized by C(max) = 123, W(50) = 4.11, and R(i) = 78.7. Addition of
      gelatin as a hydrophilic binding moiety in the first emulsion allowed PLGA-based
      microparticles to encapsulate PROLI/NO; however, the mass median diameter was too
      large for inhalation (23.5 micro m). It is concluded that the hydrophilic
      polyethylene glycol-moiety in PELA allows for efficient encapsulation of
      PROLI/NO, and PELA-based microparticles might be a strategy to generate a stable
      inhalable form of NO.

PMID- 14718182
TI  - Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying.
AB  - The encapsulation of Beijerinckia sp. cell suspension in different wall materials
      using the spray drying technique was performed. Mat dextrin, dehydrated glucose
      syrups, gum acacia and modified starch materials were tested. Cell viability
      assays were carried out before and after drying and during storage of the
      products. The surface area and characteristics of the encapsulated powders were
      examined using BET adsorption of N(2) and scanning electron microscopy,
      respectively. The residual moisture content and water activity of the powders
      were also determined. The best results were obtained with the dehydrated glucose
      syrup, which resulted in products with the greatest per cent survival during the
      drying process and subsequent storage period. The products obtained with the
      dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A(w)
      values and residual moisture content.

PMID- 14718183
TI  - Cationic stearylamine-containing biodegradable microparticles for DNA delivery.
AB  - Technical aspects for preparing a new type of cationic stearylamine (SA)
      containing microparticle as a potential drug delivery system for negatively
      charged therapeutics were investigated. Cationic biodegradable microparticles
      based on poly(lactide) and poly(lactide-co-glycolide) were prepared upon
      incorporation of SA either by solvent evaporation or by spray-drying. Water
      insoluble SA offers the advantage over other water-soluble cationic compounds
      that it can be dissolved directly in the organic solution together with the
      polymers. This facilitated the subsequent preparation of the microparticle
      formulations. Particle size was controlled by the respective process parameters,
      resulting in either large polymer aggregates within the range 50-100 micro m or
      small spherical microparticles within the range 1-10 micro m. The incorporation
      of SA into the formulations also improved particle characteristics in terms of re
      dispersibility, reduced sticking, and particle size uniformity. Both circular
      plasmid DNA (5 kbp) and linear salmon DNA (0.5 kbp) were efficiently adsorbed to
      the cationic SA microparticle surfaces. Preliminary tests on the release of DNA
      from spray-dried SA microparticles showed an immediate burst release, which was
      followed by a delayed second release phase for more than 4 weeks. The cationic SA
      microparticles might provide a potential drug-delivery system to improve the
      efficacy for protein and DNA-type therapeutics.

PMID- 14718184
TI  - Gastrointestinal absorption enhancement of insulin by administration of enteric
      microspheres and SNAC to rats.
AB  - The preparation and characteristics of insulin enteric microspheres (EMS) were
      studied and the gastrointestinal absorption enhancement of insulin by co
      administering EMS with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) was
      determined. The w/o/w and o(1)/o(2) emulsion solvent evaporation methods were
      used to prepare insulin-hydroxypropyl methylcellulose phthalate (HPMCP) EMS. High
      performance liquid chormatography determined the drug loading, entrapment
      efficiency, stability to pepsin, and drug dissolution rate in hydrochloric acid
      solution (pH 1.2) and phosphate buffer solution (pH 6.8). The hypoglycaemic
      effect was studied by orally administrating the insulin EMS and SNAC to rats. The
      particle size of EMS (o(1)/o(2)) and EMS (w/o/w) was about 500 and 30 micro m
      respectively, and drug loading was 7 and 3% respectively. After being incubated
      with 18 micro g/mL pepsin solution (pH 1) at 37 degrees C, only 20% of insulin in
      EMS (o(1)/o(2)) was digested within 4 h, while 60% of the insulin in EMS (w/o/w)
      was digested within 1 h. In hydrochloric acid solution (pH 1.2), EMS (o(1)/o(2))
      had less drug dissolution than EMS (w/o/w). In phosphate buffer solution (pH
      6.8), the entire drug release time of EMS (o(1)/o(2)) and EMS (w/o/w) was 75 and
      10 min, respectively. After orally administering with SNAC, EMS (o(1)/o(2)) could
      decrease the blood glucose level of rats remarkably and maintain the
      hypoglycaemic effect for 4 h, while EMS (w/o/w) had just a weakly hypoglycaemic
      effect. The results showed that the characteristics-optimized EMS, i.e. EMS
      (o(1)/o(2)) incorporating SNAC, could enhance insulin absorption significantly in
      the gastrointestional tract by taking advantage of both protection from enzyme
      degradation and improvement of drug permeability.

PMID- 14718185
TI  - Evaluation of enteric matrix microspheres prepared by emulsion-solvent
      evaporation using scanning electron microscopy.
AB  - Theophylline microspheres were prepared by the emulsion-solvent evaporation
      method using cellulose acetate butyrate (CAB381-20) and mixtures of CAB381-20(R)
      and cellulose acetate phthalate. The physical state of the drug, polymers and
      microspheres surfaces were determined using scanning electron microscopy. For
      those microspheres prepared using mixtures of CAB381-20 and cellulose acetate
      phthalate, scanning electron micrographs were taken before dissolution and also
      at different stages of dissolution (in SGF, pH 1.2 and in simulated intestinal
      fluid, pH 7.5). Micrographs were taken of the outside surfaces of the
      microspheres and of the cleaved microspheres showing their interiors (core). Drug
      crystals were observed on or near the surface of microspheres prepared from the
      polymer mixtures, while no drug particles or crystals were seen on the surfaces
      of microspheres prepared solely from CAB381-20. An acid wash for less than 2 min
      was capable of extracting all drug on the surface of the microspheres prepared
      from a mixture of CAB381-20 and cellulose acetate phthalate. The absence of drug
      crystals on the surface of CAB381-20 microspheres is believed to prevent initial
      drug release and create a lag time in release profiles. Results suggest that in
      both microsphere formulations, a layer of drug-free polymer is formed outside the
      core matrix and is believed to be responsible for the near zero-order release
      profiles.

PMID- 14718186
TI  - Microcapsules based on glycinin-sodium dodecyl sulfate complex coacervation.
AB  - Microcapsules processed by complex coacervation were prepared using hexadecane
      for the oil phase and glycinin (a soybean storage protein)-sodium dodecyl sulfate
      (SDS) as the main wall-forming material. The study underlines the essential role
      of SDS, which, by the way of [glycinin(+)-SDS(-)] insoluble complex formation,
      allowed the precipitation of proteins around oil droplets. Moreover, particular
      attention was attributed to the study of suitable conditions of glycinin cross
      linking with glutaraldehyde. The reticulation step was performed at pH 4.0 and it
      was observed that the precipitated state of proteins increased considerably the
      efficiency of the cross-linking reaction. Analysis of the reactional medium after
      each main step of the process (emulsification, complex coacervation, cross
      linking) allowed the follow-up and characterization of microcapsule formation.
      Optimization of different process parameters such as glycinin concentration,
      glycinin/SDS/glutaraldehyde ratios, pH and the kinetics of cross-linking allowed
      the encapsulation of the totality of oil and the use of more than 98% of
      initially introduced proteins for the microcapsule wall formation.

PMID- 14718187
TI  - Design and in vitro evaluation of gentamicin-Eudragit microspheres intended for
      intra-ocular administration.
AB  - The conditions of preparation of gentamicin sulfate microspheres with high drug
      loading and a particle size less than 5 micro m, using a double-emulsion-solvent
      evaporation technique, intended for intra-ocular administration are described.
      The microspheres were prepared from poly methacrylate (Eudragit RS and RL)
      polymers cross-linked with polyvinyl alcohol. The parameters that improved the
      incorporation efficiency of gentamicin in the microspheres and controlled the
      particle size and surface morphology were investigated. Modifying the secondary
      aqueous phase by partially saturating it with various concentrations of either
      KCl or gentamicin increased the incorporation efficiency of the drug and affected
      the mean diameters of the microspheres. However, these characteristics were not
      altered when the initial drug loading was increased in the formulations. The
      modified gentamicin microspheres exhibited a smooth surface with an incorporation
      efficiency rate of 12.59% and a mean diameter of 4.06 micro m. The antimicrobial
      efficiency of gentamicin released from the modified particles against selected
      Gram-positive and -negative organisms including Escherichia coli, Staphylococcus
      aureus and Pseudomonas aeruginosa confirmed that the entrapped gentamicin seemed
      to remain unaltered by the encapsulation process.

PMID- 14718188
TI  - Preparation and evaluation of microcapsules using polymerized rosin as a novel
      wall forming material.
AB  - Sustained release diclofenac sodium microcapsules were prepared using polymerized
      rosin as a novel wall-forming material by a solvent evaporation technique. A
      novel method developed in our laboratory with the potential for scale-up and
      production of polymerized rosin microcapsules is detailed. These microcapsules
      might have application for development of implant/depot systems, primarily due to
      a sustained/controlled release capability and potential biocompatibility of
      polymerized rosin. The effect of variables like solvent systems, stirring speed
      and temperature were previously optimized. The solution system of drug and
      polymerized rosin dissolved in iso-propyl alcohol and acetone is sprayed with the
      help of a 0.5 mm nozzle spray gun in liquid paraffin maintained at 60 degrees C
      in the stirring condition. Varying drug:polymer ratios, namely 1:1, 1:2, 2:1, 1:3
      and 3:1, were employed for microcapsule preparation. The prepared microcapsules
      were evaluated for size, shape, drug content and in vitro drug release. The
      morphology of microcapsules was characterized by scanning electron microscopy.
      The microcapsules show sustained release curves at pH 7.4 phosphate buffer for up
      to 10 h. The data obtained from the dissolution profiles were compared in the
      light of different kinetics models and the regression coefficients were compared.
      The in vitro dissolution study confirmed the Higuchi-order release pattern.
      Particle size and release data analysis from five consecutive batches prepared in
      the laboratory indicated suitable reproducibility of the proposed solvent
      evaporation process.

PMID- 14718191
TI  - Literature alerts.

PMID- 14718189
TI  - Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles:
      in vitro release and oral vaccination.
AB  - An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral
      vaccine delivery systems for improved vaccine bioavailability and increased
      therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50
      poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and
      poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method.
      VC was successfully entrapped in three types of microparticles with loading
      efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 +/-
      6.9 micro g/mg; 75:25 PLG systems: 89.2% and 46.5 +/- 4.4 micro g/mg; PLA/PEG
      blended systems: 82.6% and 53.7 +/- 5.8 micro g/mg. The different distributions
      of VC in the core region and on the surface were as follows: 50:50 PLG systems
      25.7 +/- 1.9 and 6.2 +/- 0.9 micro g/mg; 75:25 PLG systems: 25.8 +/- 2.2 and 3.6
      +/- 0.4 micro g/mg; PLA/PEG-blended systems: 32.4 +/- 2.1 and 5.2 +/- 1.0 micro
      g/mg, respectively. In vitro active release of VC was affected mainly by matrix
      type and VC-loaded location in microparticles. The therapeutic immunogenic
      potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended
      microparticles was evaluated in adult mice by oral immunization. Significantly
      higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were
      obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended
      microparticles immunized mice were titrated against VC. The most immunogenicity
      in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG
      blended microparticles, and with VC challenge in mice, the survival rate (91.7%).

PMID- 14718194
TI  - National Strategic Programme for IT within the NHS (NPfIT).

PMID- 14718195
TI  - Early examples of art in Scottish hospitals, 2: Crichton Royal Hospital,
      Dumfries.
AB  - Fine art has been used in hospitals for centuries. However, Crichton Royal
      Hospital in Dumfries pioneered the use of art activity in the treatment of its
      patients. This article is the second of two which look at examples of art created
      for, and in, Scottish hospitals in the 19th century. It is suggested that the
      importance of Scotland's contribution to this movement is unrecognized by many of
      its modern-day practitioners.

PMID- 14718196
TI  - What's in a name? Biomedical photographic communications?
AB  - The Biomedical Photographic Communications Department at the Rochester Institute
      of Technology currently offers the only university-based degree programme in this
      field in the United States. With an enrollment of more than eighty students, the
      curriculum and its delivery are continually challenged by the 'new world' of
      imaging and the needs of the increasingly diversified industry where its
      graduates are finding employment. This paper reports on a recent self-study of
      the programme and examines the future directions for educating tomorrow's
      information imaging professionals. In particular, the paper evaluates the name of
      the department, which has become both an asset and liability in describing the
      programme to perspective students.

PMID- 14718197
TI  - 'URL 404 File Not Found': dealing with the transient nature of the Web.
AB  - The 'URL File Not Found' message is all too familiar to users seeking biomedical
      information on the Web, and occurs when a requested Web-site is no longer
      available. The complex and dynamic nature of information flow is grounded in
      computer server technologies and makes the Web difficult to preserve.
      Enhancements in Web-technologies are helping to improve the problem of Web-site
      transience. Some initiatives to manage Web-site loss include Google's memory
      cache, the Internet Archive with Wayback Machine, and Web-site recording tools
      such as Internet Researcher.

PMID- 14718198
TI  - I want a design that will appeal to: older people/minority ethnic
      groups/women/disabled people/everyone...(delete as appropriate).

PMID- 14718199
TI  - Medical illustration and medical education.

PMID- 14718200
TI  - Publication and peer recognition.

PMID- 14718206
TI  - Digital images and animation in PowerPoint.

PMID- 14718210
TI  - Mesothelioma trends in the United States: an update based on Surveillance,
      Epidemiology, and End Results Program data for 1973 through 2003.
AB  - Using 1973-2000 mesothelioma incidence data released by the Surveillance,
      Epidemiology, and End Results Program in April 2003, the authors estimated the
      parameters of a birth-cohort and age model to determine whether previously
      reported patterns of mesothelioma in the United States have changed. Compared
      with analyses based on data through 1992, a slower decline was found in male
      cases immediately after a peak in 2000-2004, but no other notable changes in the
      time pattern were detected. Analysis confirmed that the annual number of male
      mesothelioma cases, which increased steeply from the 1970s through the mid-1990s,
      has leveled off in terms of both the age-adjusted rate and the absolute numbers
      of cases. After a peak of approximately 2,000 cases, a return to background
      levels is expected by 2055. The total projected number of male mesothelioma cases
      in 2003-2054 is approximately 71,000. The maximum lifetime risk for males, which
      occurs for the 1925-1929 birth cohort, is 1.8 x 10(-3). The age-adjusted rate for
      females is constant, as are the female lifetime mesothelioma risk across birth
      cohorts (3.6 x 10(-4)) and the annual risk (3.9 x 10(-6)). The time pattern of
      cases for females supports the existence of a threshold exposure for mesothelioma
      and a quantifiable background rate.

PMID- 14718212
TI  - Invited commentary: uterine leiomyomata-we know so little but could learn so
      much.

PMID- 14718213
TI  - Prospective study of the effect of exposure to other smokers in high school tutor
      groups on the risk of incident smoking in adolescence.
AB  - Adolescent smokers tend to have peers who smoke, but it is unclear whether this
      arises from self-selection of smoking peers or whether this is a causal effect on
      the uptake of smoking (incident smoking). The authors used school tutor group
      current smoking prevalence, an unbiased measure of peer smoking in high schools
      in the United Kingdom, to estimate the independent effect of peer smoking on
      incident smoking among high school students. In a prospective cohort study of
      children aged 13-15 years (grades 9 and 10) in 10 high schools in
      Nottinghamshire, United Kingdom, smoking behavior was surveyed in 2,881 students
      in 2000, and the survey was repeated in 2,109 students (73%) in 2001. There were
      267 incident smokers (15%) among the 1,766 nonsmokers in 2000. The adjusted odds
      of incident smoking were significantly higher in girls, in students with parents
      or siblings who smoke, and in relation to school tutor group current smoking
      prevalence in 2000 (relative odds for highest relative to the lowest quartile of
      prevalence = 1.78, 95% confidence interval: 1.20, 2.64). This tutor group effect
      was independent of having a best friend who smoked in the 2001 study. Incident
      smoking is therefore increased among students exposed to other students who
      smoke, and preventing smoking at school may reduce adolescent smoking.

PMID- 14718211
TI  - Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in
      African-American women: a prospective study.
AB  - The authors assessed the risk of uterine leiomyomata in relation to reproductive
      factors and hormonal contraception in a prospective cohort study of US Black
      women. From March 1997 through March 2001, the authors followed 22,895
      premenopausal women with intact uteri and no prior self-reported diagnosis of
      uterine leiomyomata. The authors used age- and time-stratified Cox regression
      models to estimate incidence rate ratios for self-reported uterine leiomyomata,
      confirmed by ultrasound or hysterectomy, in association with selected
      reproductive and hormonal factors. During 76,711 person-years of follow-up, 2,279
      new cases of ultrasound- or hysterectomy-confirmed uterine leiomyomata were self
      reported. After adjustment for age, body mass index, smoking, alcohol intake, and
      other reproductive covariates, the risk of ultrasound- or hysterectomy-confirmed
      leiomyomata was inversely associated with age at menarche, parity, and age at
      first birth and positively associated with years since last birth. Overweight or
      obesity appeared to attenuate the inverse association between parity and uterine
      leiomyomata. Current use of progestin-only injectables was inversely associated
      with risk. No consistent patterns were observed for other forms of hormonal
      contraception. Reproductive history is an important determinant of leiomyomata
      risk in premenopausal US Black women. Progestin-only injectables may reduce risk.

PMID- 14718214
TI  - Cigarette smoking and increased risk of mucinous epithelial ovarian cancer.
AB  - Several studies have reported that cigarette smoking is associated with an
      increased risk of mucinous ovarian cancer, but other studies have failed to find
      such a relation. Using data from the Case-Control Surveillance Study, begun in
      four US cities in 1976, the authors conducted a case-control study (1976-2001) to
      examine the association between cigarette smoking and the risk of ovarian cancer
      of different cell types. Among 709 incident cases of epithelial ovarian cancer,
      402 were serous, 74 were mucinous, 106 were endometrioid, and 127 were of other
      cell types. For mucinous ovarian cancer, the odds ratios were 1.5 (95% confidence
      interval (CI): 0.7, 3.4) among women who smoked less than one pack of cigarettes
      per day, 1.4 (95% CI: 0.6, 3.5) among women who smoked one pack per day, and 2.9
      (95% CI: 1.2, 7.5) among women who smoked more than one pack per day, relative to
      never smokers. The odds ratios were 2.5 (95% CI: 1.1, 5.4) for ex-smokers and 1.4
      (95% CI: 0.7, 2.9) for current smokers. While women with up to 15 pack-years of
      smoking had an almost 2.5 times' increased risk of mucinous ovarian cancer, such
      an increased risk was not found among those with more than 15 pack-years of
      smoking. There was no association between cigarette smoking and epithelial
      ovarian cancer of other cell types. Despite inconsistencies in the data, these
      results strengthen the evidence that cigarette smoking may play a role in the
      development of mucinous ovarian cancer but not ovarian cancer of other cell
      types.

PMID- 14718215
TI  - Does mammographic density reflect ethnic differences in breast cancer incidence
      rates?
AB  - Breast cancer incidence rates in the United States are substantially lower among
      Asian-American women than among White or African-American women. The authors
      determined whether mammographic density reflects these ethnic differences by
      evaluating mammograms from 442 White, African-American, and Asian-American women
      without breast cancer who served as controls in one of two population-based,
      breast cancer case-control studies conducted in Los Angeles, California, in 1994
      1998. Absolute and percent mammographic densities were determined with a
      previously developed and validated computer-assisted method. Data were analyzed
      using multiple regression methods. Mean age-adjusted percent mammographic density
      was significantly higher in Asian Americans (35.9%) than in African Americans
      (27.8%, p < 0.05) but was no longer significant after further adjustment for body
      mass index. After adjustment for age, body mass index, selected
      menstrual/reproductive factors, and family history, absolute mammographic density
      was statistically significantly lower in Asian Americans than in African
      Americans (p < 0.05) but not than in Whites. The ethnic difference in absolute
      mammographic density was particularly evident among women older than age 50
      years. Additional adjustment for breast size reduced these ethnic differences.
      This study suggests that absolute but not percent mammographic density reflects
      the lower breast cancer incidence rates of Asian Americans in relation to those
      of African Americans and Whites.

PMID- 14718216
TI  - Hair-coloring product use and risk of non-Hodgkin's lymphoma: a population-based
      case-control study in Connecticut.
AB  - A population-based case-control study was conducted in Connecticut in 1996-2002
      to test the hypothesis that lifetime hair-coloring product use increases non
      Hodgkin's lymphoma risk. A total of 601 histologically confirmed incident female
      cases and 717 population-based controls were included in the study. An increased
      risk of non-Hodgkin's lymphoma was observed among women who reported use of hair
      coloring products before 1980 (odds ratio = 1.3, 95% confidence interval (CI):
      1.0, 1.8). The odds ratios were 2.1 (95% CI: 1.0, 4.0) for those using darker
      permanent hair-coloring products for more than 25 years and 1.7 (95% CI: 1.0,
      2.8) for those who had more than 200 applications. Follicular type, B-cell, and
      low-grade lymphoma generally showed an increased risk. On the other hand, the
      authors found no increased risk of non-Hodgkin's lymphoma overall and by subtype
      of exposure and disease among women who started using hair-coloring products in
      1980 or later. It is currently unknown why an increased risk of non-Hodgkin's
      lymphoma was found only among women who started using hair-coloring products
      before 1980. Further studies are warranted to show whether the observed
      association reflects the change in hair dye formula contents during the past two
      decades or indicates that recent users are still in their induction and latent
      periods.

PMID- 14718217
TI  - Alcohol consumption during pregnancy and the risk of preterm delivery.
AB  - The authors evaluated the association between amount and type of alcohol consumed
      during pregnancy and the risk of preterm delivery and whether the relation
      differs among very (<32 completed weeks) and moderate (from 32 to <37 completed
      weeks) preterm delivery. The study is based on data of 40,892 pregnant women
      included in the first part of the Danish National Birth Cohort. The women
      completed a computer-assisted telephone interview between December 12, 1997, and
      December 31, 2000, and delivered a liveborn singleton. Of these women, 1,880 gave
      birth preterm. Compared with those who abstained during pregnancy, the relative
      risks for preterm delivery among women who consumed from four to less than seven
      drinks and seven or more drinks per week during pregnancy were 1.15 (95%
      confidence interval: 0.84, 1.57) and 1.77 (95% confidence interval: 0.94, 3.31),
      respectively. Below these intake levels of alcohol, no increased risk of preterm
      delivery was found. Among women who consumed seven or more drinks per week, the
      relative risk of very preterm delivery was 3.26 (95% confidence interval: 0.80,
      13.24) compared with that of nondrinkers. There were no differences in the
      associations between type of beverage and preterm delivery.

PMID- 14718218
TI  - Childbearing and the risk of scleroderma: a population-based study in Sweden.
AB  - This study examined associations between childbearing and risk of scleroderma by
      using national population-based registry data from Sweden. Women with a discharge
      diagnosis of scleroderma from 1964 to 1999 (n = 2,149) were identified in the
      Swedish Inpatient Register. These cases were matched by year and month of birth
      and region of residence to as many as five controls obtained from the Multi
      Generation Register. Pregnancy history (number of births, age at each birth) was
      restricted to births before the first scleroderma-related hospitalization for
      cases and the corresponding age for their matched controls. Risk estimates,
      measured by the odds ratio and 95% confidence interval, were obtained by using
      conditional logistic regression. Nulliparity was associated with an increased
      risk of scleroderma (odds ratio = 1.37, 95% confidence interval: 1.22, 1.55).
      Risk decreased with increasing number of births. Similar results were found when
      analyses were limited to births up to 2 years or up to 5 years before
      hospitalization. Among parous women, younger age at first birth was associated
      with an increased risk of scleroderma. The association between lower parity and
      increased risk of scleroderma could reflect subfecundity caused by scleroderma
      before disease became clinically evident, possible common causes of infertility
      and scleroderma, or a protective effect of pregnancy through an unknown
      mechanism.

PMID- 14718219
TI  - Social integration and mortality: a prospective study of French employees of
      Electricity of France-Gas of France: the GAZEL Cohort.
AB  - The authors investigated associations between social integration and all-cause
      and cause-specific mortality among French employees of Electricity of France-Gas
      of France. A total of 12,347 men aged 40-50 years in 1989 and 4,352 women aged 35
      50 years in 1989 comprised the sample. In age-adjusted survival analyses for all
      causes of death, men who were least socially integrated were 4.42 times as likely
      to die during follow-up (1993-1999) as those with the highest level of
      integration (p < 0.0001). After adjustment for age, occupation, smoking, alcohol
      consumption, body mass index, self-reported health, depressive symptoms, and
      region of France, relative risks for men ranging from the least socially
      integrated to the most socially integrated were 2.70 (95% confidence interval
      (CI): 1.17, 6.23), 1.95 (95% CI: 1.25, 3.04), and 1.37 (95% CI: 0.92, 2.04) in
      comparison with the most integrated men. In multivariate cause-specific analyses,
      isolated men had elevated risks of dying from cancer (relative risk = 3.60) and
      from accidents and suicide (relative risk = 3.54). Among women, in multivariate
      analyses, the relative risk was 3.64 (95% CI: 0.72, 18.58). The small number of
      deaths among women (n = 29) limited statistical power and prohibited cause
      specific analyses. These results suggest that in this employed cohort of middle
      aged men and women, social integration is an important predictor of mortality.

PMID- 14718220
TI  - Relation of education and occupation-based socioeconomic status to incident
      Alzheimer's disease.
AB  - In this study, the authors evaluated whether the association between low
      educational level and increased risk of Alzheimer's disease (AD) and dementia may
      be explained by occupation-based socioeconomic status (SES). A cohort of 931
      nondemented subjects aged > or = 75 years from the Kungsholmen Project,
      Stockholm, Sweden, was followed for 3 years between 1987 and 1993. A total of 101
      incident cases of dementia, 76 involving AD, were detected. Less-educated
      subjects had an adjusted relative risk of developing AD of 3.4 (95% confidence
      interval: 2.0, 6.0), and subjects with lower SES had an adjusted relative risk of
      1.6 (95% confidence interval: 1.0, 2.5). When both education and SES were
      introduced into the same model, only education remained significantly associated
      with AD. Combinations of low education with low or high SES were associated with
      similar increased risks of AD, but well-educated subjects with low SES were not
      at high risk. Low SES at 20 years of age, even when SES was high at age 40 or 60
      years, was associated with increased risk; however, this increase disappeared
      when education was entered into the model. In conclusion, the association between
      low education and increased AD risk was not mediated by adult SES or
      socioeconomic mobility. This suggests that early life factors may be relevant.

PMID- 14718221
TI  - Contrasting socioeconomic profiles related to healthier lifestyles in China and
      the United States.
AB  - Health disparity by socioeconomic status has recently become an important public
      health concern. Socioeconomic status may affect health status through several
      pathways including lifestyle choices. The authors tested the link between
      socioeconomic status and lifestyle in China (in 1993) and in the United States
      (in 1994-1996), countries with high contrasts in development, to understand
      health discrepancy issues cross-nationally. Healthfulness of lifestyle was
      measured using the Lifestyle Index, a summary score that integrates four key
      lifestyle factors: diet, physical activity, smoking, and alcohol consumption.
      Income and education were used as indicators of socioeconomic status. In China,
      as socioeconomic status improved, lifestyle was less healthy (relative odds for
      the highest socioeconomic status group = 0.19, 95% confidence interval: 0.10,
      0.35). Conversely, in the United States, higher socioeconomic status was related
      to a healthier lifestyle (relative odds for the highest socioeconomic status
      group = 3.81, 95% confidence interval: 2.94, 4.94). The contrasting relation
      between socioeconomic status and lifestyle depicts different phases of the
      lifestyle transition (changes in lifestyles accompanying economic development).
      The differences may in part explain why nutrition-related noncommunicable
      diseases are more prevalent in the developing world among people with a high
      socioeconomic status, whereas often the opposite is found in developed societies.
      Public health programs may benefit by advising each socioeconomic status group
      separately, while considering the country's level of development.

PMID- 14718222
TI  - Characteristics of fallers who fracture at the foot, distal forearm, proximal
      humerus, pelvis, and shaft of the tibia/fibula compared with fallers who do not
      fracture.
AB  - This case-control study examined the relation of circumstances of falls and
      characteristics of fallers with risk of fractures at five sites among persons 45
      years of age or older from five Kaiser Permanente Medical Centers in Northern
      California from 1996 to 2001. Included were distal forearm (n = 1,016), foot (n =
      574), proximal humerus (n = 467), pelvis (n = 150), and shaft of the tibia/fibula
      (n = 141) cases who fell at the time of their fracture, and controls (n = 512)
      who reported falling in the year before the interview but did not fracture.
      Interviewers collected information by using a standardized questionnaire. Medium
      /high-heeled shoes and shoes with a narrow heel increased the risk of all
      fractures, and slip-on shoes (adjusted odds ratio = 2.3, 95% confidence interval:
      1.4, 4.0) and sandals (adjusted odds ratio = 3.1, 95% confidence interval: 1.5,
      6.3) increased the risk of foot fractures. Falling from more than a standing
      height increased the risk of all fractures by two- to fivefold, while breaking
      the fall was associated with lower risks of all fractures except the distal
      forearm. Physical activity and hormone therapy were associated with lower risks
      of most fractures. These results suggest ways in which risks of fractures in
      older persons can be reduced.

PMID- 14718223
TI  - Studies with low response proportions may be less biased than studies with high
      response proportions.
AB  - The association between the response proportion in epidemiologic studies and
      nonresponse bias is complicated, because exposure prevalences and
      misclassification errors may vary by recruitment wave. In this paper, the authors
      illustrate the effect of varying degrees of wave-specific nondifferential
      exposure measurement error in a dichotomous exposure on the relative risk in a
      hypothetical cohort study of 5,000 participants, by recruitment wave. The field
      phase of the hypothetical cohort study consisted of five consecutive recruitment
      waves. The authors assigned response proportions to each wave (wave 1: 30%; wave
      2: 10%; wave 3: 10%; wave 4: 30%; wave 5: 20%) and studied three different wave
      specific patterns of true exposure prevalence: 1) the true exposure prevalence
      remains the same in all waves; 2) the true exposure prevalence increases by wave;
      and 3) the true exposure prevalence decreases by wave. The authors assumed three
      corresponding patterns of nondifferential misclassification error in exposure
      status across waves. If the nondifferential exposure misclassification increases
      by wave, the cumulative relative risk estimate is increasingly biased towards the
      null. This bias is intensified if the true exposure prevalence increases by wave.
      Studies with low response proportions may be less biased than studies with high
      response proportions if the nondifferential misclassification error in a
      dichotomous exposure increases by recruitment wave.

PMID- 14718224
TI  - Re: "Estimating the relative risk in cohort studies and clinical trials of common
      outcomes".

PMID- 14718225
TI  - Re: "Estimating the relative risk in cohort studies and clinical trials of common
      outcomes".

PMID- 14718227
TI  - Improvement of metabolic function in sleep apnea: the power of positive pressure.

PMID- 14718228
TI  - Evaluating the upper airway during wakefulness: what can it tell us about sleep?

PMID- 14718229
TI  - Cystic fibrosis patients, infertile men, and their noses.

PMID- 14718230
TI  - Clara cell protein in sarcoidosis: another job for the respiratory tract
      protector?

PMID- 14718231
TI  - Sepsis and innate immunity.

PMID- 14718232
TI  - Peroxisome proliferator-active receptor gamma: a legitimate target to control
      pulmonary inflammation?

PMID- 14718233
TI  - Pro: Sleep apnea causes cardiovascular disease.

PMID- 14718234
TI  - Con: Sleep apnea does not cause cardiovascular disease.

PMID- 14718237
TI  - Clinical usefulness of respiratory variations in arterial pressure.

PMID- 14718238
TI  - Critical care medicine in AJRCCM 2003.

PMID- 14718239
TI  - Sleep-disordered breathing, control of breathing, respiratory muscles, pulmonary
      function testing in AJRCCM 2003.

PMID- 14718240
TI  - Asthma, airway biology, and nasal disorders in AJRCCM 2003.

PMID- 14718241
TI  - Pediatrics, surfactant, and cystic fibrosis in AJRCCM 2003.

PMID- 14718242
TI  - Tuberculosis, lung infections, interstitial lung disease, social issues and
      journalology in AJRCCM 2003.

PMID- 14718243
TI  - Chronic obstructive pulmonary disease, pollution, pulmonary vascular disease,
      transplantation, pleural disease, and lung cancer in AJRCCM 2003.

PMID- 14718244
TI  - Biotrauma hypothesis of ventilator-induced lung injury.

PMID- 14718245
TI  - Statements of ATS, CDC, and IDSA on treatment of tuberculosis.

PMID- 14718246
TI  - Nose and blood pressure.

PMID- 14718247
TI  - Cystic fibrosis and NOS3.

PMID- 14718248
TI  - Effect of ambient air pollution on pulmonary exacerbations and lung function in
      cystic fibrosis.
AB  - Information concerning the impact of environmental factors on cystic fibrosis
      (CF) is limited. We conducted a cohort study to assess the impact of air
      pollutants in CF. The study included patients over the age of 6 years enrolled in
      the Cystic Fibrosis Foundation National Patient Registry in 1999 and 2000.
      Exposure was assessed by linking air pollution values from the Aerometric
      Information Retrieval System with the patients' home zip code. After adjusting
      for confounders, a 10 microg/m(3) rise in particulate matter (both with a median
      aerodynamic diameter of 10 microm (PM(10)) or less and with an aerodynamic
      diameter of 2.5 microm or less (PM(2.5)) was associated with an 8% (95%
      confidence interval [CI], 2-15%) and 21% (95% CI, 7-33%) increase in the odds of
      two or more exacerbations, respectively; a 10-ppb rise in ozone was associated
      with a 10% (95% CI, 3-17%) increase in odds of two or more exacerbations. For
      every increase in PM(2.5) of 10 microg/m(3), there was an associated fall in
      FEV(1) of 24 ml (7-40) (95% CI) after adjusting for confounders. PM(2.5)'s
      association with mortality did not achieve statistical significance (adjusted RR
      = 1.32 per 10 microg/m(3) 0.91-1.93; 95% CI). Annual average exposures to
      particulate air pollution was associated with an increased risk of pulmonary
      exacerbations and a decline in lung function, suggesting a role of environmental
      exposures on prognosis in CF.

PMID- 14718249
TI  - Structure-activity analysis of a novel NR2C/NR2D-preferring NMDA receptor
      antagonist: 1-(phenanthrene-2-carbonyl) piperazine-2,3-dicarboxylic acid.
AB  - (2S*,3R*)-1-(biphenyl-4-carbonyl)piperazine-2,3-dicarboxylic acid (PBPD) is a
      moderate affinity, competitive N-methyl-d-aspartate (NMDA) receptor antagonist
      with an atypical pattern of selectivity among NMDA receptor 2 subunit (NR2)
      subunits. We now describe the activity of several derivatives of PBPD tested at
      both rat brain NMDA receptors using l-[3H]-glutamate binding assays and at
      recombinant receptors expressed in Xenopus oocytes. Substituting various branched
      ring structures for the biphenyl group of PBPD reduced NMDA receptor activity.
      However, substituting linearly arranged ring structures - fluorenone or
      phenanthrene groups - retained or enhanced activity. Relative to PBPD, the
      phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3
      dicarboxylic acid (PPDA) displayed a 30- to 78-fold increase in affinity for
      native NMDA receptors. At recombinant receptors, PPDA displayed a 16-fold (NR2B)
      to 94-fold (NR2C) increase in affinity over PBPD. Replacement of the biphenyl
      group of PBPD with a 9-oxofluorene ring system resulted in small changes in
      receptor affinity and subtype selectivity. 2'-Bromo substitution on the biphenyl
      group of PBPD reduced antagonist affinity 3- to 5-fold at NR2A-, NR2B- and NR2D
      containing receptors, but had little effect on NR2C-containing receptors. In
      contrast, 4'-fluoro substitution of the biphenyl ring of PBPD selectively
      increased NR2A affinity. The aromatic rings of PBPD and PPDA increase antagonist
      affinity and appear to interact with a region of the NMDA receptor displaying
      subunit heterogeneity. PPDA is the most potent and selective NR2C/NR2D-preferring
      antagonist yet reported and thus may be useful in defining NR2C/NR2D function and
      developing related antagonists with improved NMDA receptor subtype selectivity.
      British Journal of Pharmacology (2004) 141, 508-516. doi:10.1038/sj.bjp.0705644

PMID- 14718250
TI  - The contractile action of leukotriene B4 in the guinea-pig lung involves a
      vascular component.
AB  - Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific
      receptors, BLT receptors. The aim of this study was to examine the mechanism of
      action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP),
      spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA).
      Mechanical responses were studied in organ baths, and mediator release was
      assessed using enzyme immuno assay. LTB4 induced similar contractions of GPLP and
      GPPA, whereas LTB4 had only small contractile effects in GPT and GPB. In
      addition, the contractile response to LTB4 was reproduced in the human pulmonary
      artery. In the GPLP, the unselective BLT receptor antagonist ONO-4057 abolished
      the contractions induced by LTB4, whereas the selective BLT1 receptor antagonist
      U-75302 only partly inhibited the LTB4-induced contractions. In the GPPA, both
      antagonists abolished the response to LTB4. The effect of LTB4 in GPPA and GPLP
      was indirect and mediated by the release of thromboxane A2 and histamine, as
      supported by selective pharmacologic interventions and measurements of
      thromboxane B2 and histamine in the organ baths. In conclusion, the results
      indicate a new biological function of LTB4, namely to constrict isolated
      pulmonary arteries. Moreover, the findings suggest that the LTB4-induced
      contractions of GPPA were mediated by a BLT1 receptor, whereas BLT2 receptor
      activation accounted for a major part of the contraction of GPLP, making the
      latter preparation a suitable assay for BLT2 receptors. British Journal of
      Pharmacology (2004) 141, 449-456. doi:10.1038/sj.bjp.0705641

PMID- 14718251
TI  - Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat
      preglomerular microvessels (PGMV) via A2A receptors.
AB  - Activation of rat adenosine2A receptors (A2A R) dilates preglomerular
      microvessels (PGMV), an effect mediated by epoxyeicosatrienoic acids (EETs).
      Incubation of PGMV with a selective A2A R agonist, 2-p-(2-carboxyethyl)
      phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 100 microM), increased
      isolated PGMV EET levels to 7.57+/-1.53 ng mg-1 protein from 1.06+/-0.22 ng mg-1
      protein in controls (P<0.05), without affecting hydroxyeicosatetraenoic acid
      (HETE) levels (10.8+/-0.69 vs 11.02+/-0.74 ng mg-1 protein). CGS 21680-stimulated
      EETs was abolished by preincubation with an A2A R antagonist, 4-(2-[7-amino-2-(2
      furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) (100
      microM). A selective epoxygenase inhibitor, methylsulfonyl
      propargyloxyphenylhexanamide (MS-PPOH; 12 microM) prevented CGS 21680-induced
      increase in EETs, indicating inhibition of de novo synthesis of EETs. In
      pressurized (80 mmHg) renal arcuate arteries (110-130 microm) preconstricted with
      phenylephrine (20 nM), superfusion with CGS 21680 (0.01-10 microM) increased the
      internal diameter (i.d.) concentration-dependently; vasodilation was independent
      of nitric oxide and cyclooxygenase activity. CGS 21680 (10 microM) increased i.d.
      by 32+/-6 microm; vasodilation was prevented by inhibition of EET synthesis with
      MS-PPOH. Addition of 3 nM 5,6-EET, 8,9-EET and 11,12-EET increased i.d. by 53+/
      9, 17+/-4 and 53+/-5 microm, respectively, whereas 14,15-EET was inactive. The
      responses to 5,6-EET were, however, significantly inhibited by indomethacin. We
      conclude that 11,12-EET is the likely mediator of A2A R-induced dilation of rat
      PGMV. Activation of A2A R coupled to de novo EET stimulation may represent an
      important mechanism in regulating preglomerular microvascular tone. British
      Journal of Pharmacology (2004) 141, 441-448. doi:10.1038/sj.bjp.0705640

PMID- 14718252
TI  - Differential effects of P2Y1 and P2Y12 nucleotide receptors on ERK1/ERK2 and
      phosphatidylinositol 3-kinase signalling and cell proliferation in serum-deprived
      and nonstarved glioma C6 cells.
AB  - We have previously shown that, in glioma C6 cells, two nucleotide ADP-sensitive
      receptors coexist: P2Y1, coupled to PLC and responsible for Ca2+ release, and
      P2Y12, negatively coupled to adenylate cyclase. In the present study, we examined
      the effects of the stimulation of these two receptors on ERK1/2 and PI3-K
      activation, and cell proliferation in either serum-deprived or nonstarved C6
      cells. In response to ADP and its analogues, in serum-starved cells, both p44
      ERK1 and p42 ERK2 were activated in a time-dependent manner, as monitored by
      Western blot analysis using an antiphospho-p42/p44 MAPK antibody. The
      phosphorylation was reduced both by removal of the extracellular Ca2+ and
      partially or almost completely by MRS2179 or AR-C69931MX, specific antagonists of
      the P2Y1 and P2Y12 receptors, respectively. The inhibitory effect of antagonists
      was additive. These data indicate the involvement of both receptors, P2Y1 and
      P2Y12, in the ERK1/2 activation, but the P2Y12 receptor contribution
      predominates. ERK1/2 activity was positively correlated with cell proliferation
      of cultured glioma C6 cells. In nonstarved cells, ADP markedly decreased the PI3
      K activity. In contrast, in serum-starved cells, ADP evoked an increase in the
      PI3-K activity. Blocking of the P2Y1 receptor by MRS2179 additionally increased
      this ADP response. These results suggest that the P2Y1 receptor has an inhibitory
      and the P2Y12 receptor a stimulatory effect on PI3-K signalling pathway. RT-PCR
      analysis revealed different mRNA expression of both receptors in starved and
      nonstarved cells. In nonstarved cells, the P2Y1 receptor mRNA predominates,
      whereas in serum-deprived cells the expression of P2Y12 mRNA becomes more
      pronounced. British Journal of Pharmacology (2004) 141, 497-507.
      doi:10.1038/sj.bjp.0705639

PMID- 14718253
TI  - Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a
      model of allergic airway inflammation.
AB  - Brain-derived neurotrophic factor (BDNF) is a candidate molecule for mediating
      functional neuronal changes in allergic bronchial asthma. Recently, enhanced
      production of BDNF during allergic airway inflammation caused by infiltrating T
      cells and macrophages as well as by resident airway epithelial cells has been
      described. It was the aim of this study to investigate the effect of enhanced
      BDNF levels on lung function and airway inflammation in a mouse model of allergic
      inflammation. Ovalbumin-sensitised BALB/c mice were challenged in two consecutive
      allergen challenges. Prior to the challenge, the mice were treated with either
      anti-BDNF antibodies or isotype-matched control antibodies. Airway responsiveness
      to methacholine, capsaicin and electric field stimulation, as well as airway
      inflammation and chronic airway obstruction 1 week after the last allergen
      challenge were assessed. Anti-BDNF blocked enhanced reactivity in response to
      capsaicin, but not airway smooth muscle hyper-reactivity in vivo. Furthermore,
      persistent airway obstruction, as observed 1 week after the last allergen
      challenge, was to a large extent prevented by anti-BDNF treatment. In vitro, BDNF
      and anti-BDNF treatment had a profound effect on local neuronal hyper-reactivity,
      as shown by electric field stimulation experiments. In contrast, neither BDNF nor
      anti-BDNF treatment affected airway inflammation. Our data indicate that
      development of allergen-induced neuronal hyper-reactivity in mice is partially
      mediated by BDNF. British Journal of Pharmacology (2004) 141, 431-440.
      doi:10.1038/sj.bjp.0705638

PMID- 14718254
TI  - Dual effects of intrathecal BAM22 on nociceptive responses in acute and
      persistent pain--potential function of a novel receptor.
AB  - Bovine adrenal medulla 22 (BAM22) peptide is one of the cleavage products of
      proenkephalin A. It binds with high affinity to both opioid receptors and a newly
      discovered receptor in vitro. This latter receptor was first named sensory neuron
      specific receptor and is here named BAM peptide-activated receptor with non
      opioid activity (BPAR). BPAR is uniquely distributed in small-diameter DRG
      neurons, most of which are associated with the IB4 class of nociceptor afferent.
      The present study examined the effects of intrathecal administration of BAM22 on
      formalin-induced nocifensive behaviors and tail-withdrawal latency in the rat.
      Intrathecal (i.t.) administration of BAM22 decreased nocifensive behavior scores,
      measured as the sum of flinching and lifting/licking, in the first and second
      phases of the formalin test. This decrease was partially attenuated by systemic
      injection of naloxone. In the presence of naloxone, i.t. BAM22 produced a dose
      dependent suppression of the nocifensive behaviors observed during the formalin
      test. The ratio of the efficacy of BAM22 (5 nmol) in the presence of naloxone
      over that in the absence of naloxone was 0.65 for flinching and 0.74 for
      lifting/licking in the second phase. BAM22 at a dose of 5 nmol increased the tail
      withdrawal latency by 193 and 119% of baseline in the absence and presence of
      naloxone, respectively. Systemic administration of naloxone alone enhanced the
      nocifensive behaviors in the second, but not in the first phase of the formalin
      test. Naloxone treatment did not alter the tail-withdrawal latency. These data
      confirm earlier in vitro data showing that BAM22 has both opioid and non-opioid
      biological actions. The non-opioid action of BAM22 involves inhibition of acute
      and persistent nociceptive behaviors at the spinal level, presumably mediated via
      BPAR. The name suggested for this novel receptor, its potential physiological
      function and its ligand are discussed. British Journal of Pharmacology (2004)
      141, 423-430. doi:10.1038/sj.bjp.0705637

PMID- 14718255
TI  - 3,5-Dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7) as a new
      multidrug resistance reverting agent devoid of effects on vascular smooth muscle
      contractility.
AB  - The aim of this study was to investigate the effects of 3,5-diacetyl- (DP1-DP5)
      and 3,5-dibenzoyl-1,4-dihydropyridines (DP6-DP11) on vascular functions in vitro,
      by comparing their mechanical and electrophysiological actions in rat aorta rings
      and single rat tail artery myocytes, respectively, and to quantify their
      multidrug resistance (MDR)-reversing activity in L5178 Y mouse T-lymphoma cells
      transfected with MDR1 gene. In rat aorta, the 11 compounds tested, but 3,5
      dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7), 3,5
      dibenzoyl-4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (DP9), 3,5
      dibenzoyl-4-(4-chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (DP10) and 3,5
      dibenzoyl-4-phenyl-1,4-dihydro-2,6-dimethylpyridine (DP11), antagonized 60 mm K+
      (K60)-induced contraction in a concentration-dependent manner, with IC50 (m)
      values ranging between 5.65 x 10(-7) and 2.23 x 10(-5). The 11 dihydropyridines
      tested, but DP7, inhibited L-type Ca2+ current recorded in artery myocytes in a
      concentration-dependent manner, with IC50 (M) values ranging between 1.12 x 10(
      6) and 6.90 x 10(-5). The K+ -channel opener cromakalim inhibited the Ca2+ 
      induced contraction in K30 but not that evoked in K60. On the contrary, DP7 was
      ineffective in both experimental conditions. When the rings were preincubated
      with 1 mm Ni2+ plus 1 microm nifedipine, the response to phenylephrine was
      significantly reduced by 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ), a well-known
      endoplasmic reticulum Ca2+ -ATPase inhibitor. DP7 had no effects on this model
      system. In L5178 MDR cell line, the 11 dihydropyridines tested, but 3,5-diacetyl
      4-(2-nitrophenyl)-1,4-dihydro-2,6-dimethylpyridine (DP1), 3,5-diacetyl-4-(3
      phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP2) and 3,5-diacetyl-4-(3
      chlorophenyl)-1,4-dihydro-2,6-dimethylpyridine (DP4), exhibited an MDR-reversing
      activity, with IC50 values ranging between 3.02 x 10(-7) and 4.27 x 10(-5), DP7
      being the most potent. In conclusion, DP7 may represent a lead compound for the
      development of potent dihydropyridine MDR chemosensitizers devoid of vascular
      effects. British Journal of Pharmacology (2004) 141, 415-422.
      doi:10.1038/sj.bjp.0705635

PMID- 14718256
TI  - Octreotide regulates CC but not CXC LPS-induced chemokine secretion in rat
      Kupffer cells.
AB  - Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event
      leading to hepatic inflammation and fibrosis in many types of liver injury. We
      studied chemokine secretion by KC activated with LPS and the possible effect of
      the somatostatin analogue octreotide, in the regulation of this process. KC
      isolated from Sprague-Dawley rats were cultured in the presence of LPS added
      alone or with different concentrations of octreotide for 24 and 48 h, and
      chemokine production was assessed in culture supernatants by ELISA. CC chemokine
      mRNA expression was assessed by semiquantitative RT-PCR. Vehicle-stimulated KC
      produced a basal amount of CC and CXC chemokines. LPS-stimulated KC secreted
      significantly increased amounts of IL-8 (GRO/CINC-1) (P<0.001), MIP-2 (P<0.001),
      MCP-1 (P<0.001), and RANTES (P<0.01). Octreotide inhibited LPS-induced secretion
      of the CC chemokines MCP-1 (P<0.05) and RANTES (P<0.05), but not the CXC
      chemokines IL-8 (GRO/CINC-1) and MIP-2, in a concentration-dependent manner.
      Downregulation of basal and LPS-induced mRNA expression of the CC chemokines was
      also observed in the presence of octreotide. Pretreatment with
      phosphatidylinositol 3 (PI3)-kinase inhibitors reduced chemokine production by
      LPS-treated KC in both the mRNA and protein level. Furthermore, it prevented the
      octreotide inhibitory effect on LPS-induced chemokine secretion, indicating a
      possible involvement of the PI3-kinase pathway. In conclusion, these data
      demonstrate that chemokine secretion by KC can be differentially regulated by
      octreotide, and suggest that this somatostatin analogue may have immunoregulatory
      effects on resident liver macrophages. British Journal of Pharmacology (2004)
      141, 477-487. doi:10.1038/sj.bjp.0705633

PMID- 14718257
TI  - 5-Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine,
      which is converted into nitric oxide.
AB  - There is circumstantial evidence suggesting that 5-hydroxytryptamine (5-HT) could
      be biotransformed by enzymatic systems other than monoamino oxidase A, and that
      the isoforms of cytochrome P450 may be a source of nitric oxide. This study aimed
      to assess whether cytochrome P450 contributes to 5-HT biotransformation, and to
      provide evidence that 5-HT metabolism generates nitric oxide. Addition of 5-HT to
      cultured hepatocytes yielded 5-hydroxyindol acetic acid, a formation modulated by
      cytochrome P450 enzyme inducers and inhibitors. Recombinant human CYP2B6, 2C9 and
      2C19 biotransformed 5-HT in 5-hydroxyindol acetic acid, but not CYP1A2, 2D6 or
      3A4. Cultured hepatocytes with 5-HT generated nitric oxide, the amount of which
      was altered by cytochrome P450 enzyme inducers and inhibitors. In the presence of
      CYP2B6, 2C9 and 2C19, 5-HT relaxed precontracted isolated aortic rings, with or
      without endothelium, an effect prevented by the addition of methylene blue and an
      inhibitor of catalase, but not by myoglobin. In the absence of catalase,
      hydroxylamine was always assayed as a byproduct of 5-HT metabolism. In
      conclusion, CYP2B6, 2C9 and 2C19 biotransform 5-HT, yielding hydroxylamine, which
      is converted to nitric oxide in the presence of catalase. British Journal of
      Pharmacology (2004) 141, 407-414. doi:10.1038/sj.bjp.0705632

PMID- 14718258
TI  - Na+/H+ exchange inhibition attenuates left ventricular remodeling and preserves
      systolic function in pressure-overloaded hearts.
AB  - Cardiac hypertrophy is a homeostatic response to elevated afterload. Na+/H+
      exchanger (NHE) inhibition reduces the hypertrophic response in animal models of
      left ventricular hypertrophy (LVH) and myocardial infarction. We examined the
      effect of chronic treatment with cariporide, a selective inhibitor of Na+/H+
      exchanger isoform 1 (NHE-1), on left ventricular (LV) systolic and diastolic
      function under pressure overload conditions. Male CD-1 mice were randomized to
      receive either a control diet or an identical diet supplemented with 6000 p.p.m.
      of cariporide. Cardiac pressure overload was induced by thoracic aortic banding.
      LV dimension and systolic and diastolic function were assessed in sham and banded
      mice by echocardiography and cardiac catheterization 2 and 5 weeks after surgery.
      Histological analysis was also performed. After 2 weeks of pressure overload, the
      vehicle-treated banded mice (Veh-Bd) had enhanced normalized LV weight (about
      +50%) and normal chamber size and function, whereas cariporide-treated banded
      mice (Car-Bd) showed a preserved contractility and systolic function despite a
      marked attenuation of LVH. Diastolic function did not differ significantly among
      groups. After 5 weeks, the Veh-Bd developed LV chamber enlargement and systolic
      dysfunction as evidenced by a 16% increase in LV end-diastolic diameter, a 36%
      decrease in myocardial contractility, and a 26% reduction in percent fractional
      shortening. In contrast, Car-Bd showed an attenuated increase in LV mass, normal
      chamber size, and a maintained systolic function. A distinct histological feature
      was that in banded mice, cariporide attenuated the development of cardiomyocyte
      hypertrophy but not the attendant myocardial fibrosis. In conclusion, the results
      of the present study indicate that (i) the hypertrophic response to pressure
      overload is dependent on NHE-1 activity, and (ii) at the 5-week stage, banding
      induced deterioration of LV performance is prevented by NHE-1 inhibition.British
      Journal of Pharmacology (2004) 141, 526-532. doi:10.1038/sj.bjp.0705631

PMID- 14718259
TI  - PPAR gamma ligands, 15-deoxy-delta12,14-prostaglandin J2 and rosiglitazone
      regulate human cultured airway smooth muscle proliferation through different
      mechanisms.
AB  - The influence of two peroxisome proliferator-activated receptor gamma (PPARgamma)
      ligands, a thiazolidinedione, rosiglitazone (RG) and the prostaglandin D2
      metabolite 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) on the proliferation
      of human cultured airway smooth muscle (HASM) was examined. The increases in HASM
      cell number in response to basic fibroblast growth factor (bFGF, 300 pm) or
      thrombin (0.3 U ml-1) were significantly inhibited by either RG (1-10 microM) or
      15d-PGJ2 (1-10 microM). The effects of RG, but not 15d-PGJ2, were reversed by the
      selective PPARgamma antagonist GW9662 (1 microM). Neither RG nor 15d-PGJ2 (10
      microM) decreased cell viability, or induced apoptosis, suggesting that the
      regulation of cell number was due to inhibition of proliferation, rather than
      increased cell death. Flow-cytometric analysis of HASM cell cycle distribution 24
      h after bFGF addition showed that RG prevented the progression of cells from G1
      to S phase. In contrast, 15d-PGJ2 caused an increase in the proportion of cells
      in S phase, and a decrease in G2/M, compared to bFGF alone. Neither RG nor 15d
      PGJ2 inhibited ERK phosphorylation measured 6 h post mitogen addition. The bFGF
      mediated increase in cyclin D1 protein levels after 8 h was reduced in the
      presence of 15d-PGJ2, but not RG. Although both RG and 15d-PGJ2 can inhibit
      proliferation of HASM irrespective of the mitogen used, only the
      antiproliferative effects of RG appear to be PPARgamma-dependent. The different
      antimitogenic mechanisms of 15d-PGJ2 and synthetic ligands for PPARgamma may be
      exploited to optimise the potential for these compounds to inhibit airway
      remodelling in asthma. British Journal of Pharmacology (2004) 141, 517-525.
      doi:10.1038/sj.bjp.0705630

PMID- 14718260
TI  - Impact of treatment with melatonin on cerebral circulation in old rats.
AB  - Melatonin deprival in young rats induces alterations in cerebral arteriolar wall
      similar to those observed during aging: atrophy and a decrease in distensibility.
      In this study, we examined the effects of melatonin treatment on cerebral
      arteriolar structure and distensibility and on the lower limit of cerebral blood
      flow autoregulation (LLCBF) in old rats. We measured cerebral blood flow
      (arbitrary unit, laser Doppler, open skull preparation) prior to and during
      stepwise hypotension (SH) in adult (12/13 months) and old (24/25 months) IcoWI
      and WAG/Rij male rats. Old rats were untreated or treated for 3 months with
      melatonin (0.39 (IcoWi) and 0.44 (Wag/Rij) mg kg-1 day-1, drinking water). Stress
      strain relationships were determined using cross-sectional area (CSA, microm2,
      histometry) and values of arteriolar internal diameter (microm) obtained during a
      second SH following arteriolar deactivation (EDTA, 67 mmol l(-1)). Aging induced
      (a) atrophy of the arteriolar wall in IcoWI (616+/-20 vs 500+/-27 microm2,
      P<0.05) but not in WAG/Rij rats (328+/-25 vs 341+/-20 microm2), (b) a decrease in
      arteriolar wall distensibility and (c) an increase in the LLCBF in both strains
      (67+/-10 mmHg in 12-month-old vs 95+/-6 mmHg in 24-month-old IcoWi, P<0.05 and
      53+/-2 mmHg in 13-month-old vs 67+/-6 mmHg in 25-month-old WAG/Rij). Melatonin
      treatment induced in IcoWI and WAG/Rij rats (a) hypertrophy of the arteriolar
      wall (643+/-34 and 435+/-25 microm2, respectively), (b) an increase in arteriolar
      wall distensibility and (c) a decrease in the LLCBF (64+/-6 and 45+/-4 mmHg,
      respectively). Melatonin treatment of old rats induced hypertrophy of the
      arteriolar wall, prevented the age-linked decrease in cerebral arteriolar
      distensibility and decreased the LLCBF. British Journal of Pharmacology (2004)
      141, 399-406. doi:10.1038/sj.bjp.0705629

PMID- 14718261
TI  - Characterization of an anandamide degradation system in prostate epithelial PC-3
      cells: synthesis of new transporter inhibitors as tools for this study.
AB  - The response of anandamide is terminated by a carrier-mediated transport followed
      by degradation catalyzed by the cloned enzyme fatty acid amidohydrolase (FAAH).
      In this study, we provide biochemical data showing an anandamide uptake process
      and the expression of FAAH in human prostate. Anandamide was accumulated in PC-3
      cells by a saturable and temperature-dependent process. Kinetic studies of
      anandamide uptake, determined in the presence of cannabinoid and vanilloid
      antagonists, revealed apparent parameters of KM=4.7+/-0.2 microm and Vmax=3.3+/
      0.3 pmol min-1 (10(6) cells)-1. The accumulation of anandamide was moderately
      inhibited by previously characterized anandamide transporter inhibitors (AM404,
      UCM707 and VDM11) but was unaffected by inhibitors of other lipid transport
      systems (phloretin or verapamil) and moderately affected by the FAAH inhibitor
      methyl arachidonyl fluorophosphonate. The presence of FAAH in human prostate
      epithelial PC-3 cells was confirmed by analyzing its expression by Western blot
      and measuring FAAH activity. To further study the structural requirements of the
      putative carrier, we synthesized a series of structurally different compounds 1-8
      and evaluated their capacity as uptake inhibitors. They showed different
      inhibitory capacity in PC-3 cells, with (9Z,12Z)-N-(fur-3-ylmethyl)octadeca-9,12
      dienamide (4, UCM119) being the most efficacious, with maximal inhibition and
      IC50 values of 49% and 11.3+/-0.5 microM, respectively. In conclusion, PC-3 cells
      possess a complete inactivation system for anandamide formed by an uptake process
      and the enzyme FAAH. These results suggest a possible physiological function of
      anandamide in the prostate, reinforcing the role of endocannabinoid system as a
      neuroendocrine modulator. British Journal of Pharmacology (2004) 141, 457-467.
      doi:10.1038/sj.bjp.0705628

PMID- 14718262
TI  - Alpha-1 adrenoceptors: evaluation of receptor subtype-binding kinetics in intact
      arterial tissues and comparison with membrane binding.
AB  - The binding kinetics of [3H]-prazosin were measured using intact segments of rat
      tail artery (RTA) and thoracic aorta (RAO), and the data were compared with those
      obtained using a conventional membrane ligand-binding method. In intact RTA and
      RAO segments, [3H]-prazosin bound reversibly in a time-dependent and receptor
      specific manner at 4 degrees C to alpha-1 adrenoceptors (ARs) of the plasma
      membrane, with affinities (pKD): 9.5 in RTA; 9.9 in RAO) that were in agreement
      with values estimated by a conventional membrane ligand-binding method. However,
      nonspecific binding was considerably higher in RAO than RTA, failing to detect
      clearly the specific binding at high concentrations (>300 pm) of [3H]-prazosin in
      binding experiments with RAO segments and membranes. The abundance of receptor in
      the RTA and RAO (Bmax mg-1) of total tissue protein), estimated using the tissue
      segment-binding approach (527+/-14 fmol mg-1 for RTA; 138+/-4 fmol mg-1 for RAO),
      was about 25-fold higher than values estimated using a conventional membrane
      binding method (22+/-5 fmol mg-1) for RTA; 5+/-1 fmol mg-1 for RAO). Binding
      competition experiments using intact tissue segments or membranes derived from
      RTA tissue yielded comparable data, indicating a coexistence of alpha-1A AR (high
      affinity for prazosin, KMD-3213 and WB4101 and low affinity for BMY 7378) and
      alpha-1B AR (high affinity for prazosin but low affinity for KMD-3213, WB4101 and
      BMY 7378). In RAO tissue, careful evaluation of the tissue segment-binding assay
      revealed the coexpression of alpha-1B AR (high affinity for prazosin, but low
      affinity for KMD-3213 and BMY 7378) and alpha-1D AR (high affinity for prazosin
      and BMY 7378, but low affinity for KMD-3213), whereas the membrane-binding
      approach failed to detect these receptor subtypes with certainty. The present
      study indicates that previous estimates of alpha-1 AR density and alpha-1 AR
      subtypes obtained by a conventional membrane-binding approach, as opposed to our
      improved tissue segment-binding assay, may have substantially underestimated the
      abundance of receptors present in arterial tissues, and may have failed to
      identify accurately the presence of receptor subtypes. Advantages and
      disadvantages of the tissue segment-binding approach are discussed.British
      Journal of Pharmacology (2004) 141, 468-476. doi:10.1038/sj.bjp.0705627

PMID- 14718263
TI  - Iloprost inhibits superoxide formation and gp91phox expression induced by the
      thromboxane A2 analogue U46619, 8-isoprostane F2alpha, prostaglandin F2alpha,
      cytokines and endotoxin in the pig pulmonary artery.
AB  - Since the roles of thromboxane A2 (TXA2), prostacyclin (PGI2) and 8-isoprostane
      F2alpha in mediating vascular O2*- formation and its relation to adult
      respiratory distress syndrome (ARDS) is unknown, the effects of these eicosanoids
      on the expression of gp91phox (catalytic subunit of NADPH oxidase) and O2*-
      release from cultured pig pulmonary artery (PA) segments, PA vascular smooth
      muscle cells (PAVSMCs) and PA endothelial cells (PAECs) were investigated. PA
      segments, PAVSMCs and PAECs were incubated with the TXA2 analogue, U46619, (+/
      LPS, tumour necrosing factor-alpha (TNF-alpha) or IL-1alpha), 8-isoprostane
      F2alpha and+/-iloprost (a stable PGI2 analogue) for 16 h. The formation of
      superoxide dismutase-inhibitable O2*- was then measured spectrophotometrically
      and gp91phox expression assessed using Western blotting. In parallel experiments,
      whole PA segments were treated with LPS, TNF-alpha and IL-alpha after which time
      TXA2, PGI2, PGF2alpha and 8-isoprostane F2alpha formation was measured using
      enzyme-linked immunoassays. U46619, PGF2alpha and 8-isoprostane F2alpha promoted
      the formation of O2*- in PA segments, PAVSMCs and PAECs, an effect inhibited by
      diphenyleneiodonium and apocynin (both NADPH oxidase inhibitors) and upregulated
      the expression of gp91phox in PAECs and PAVSMCs. These effects were augmented by
      LPS, TNF-alpha and IL-1alpha but inhibited by iloprost. Under identical
      incubation conditions, IL-1alpha, LPS and TNF-alpha all induced an increase in
      the formation of TXA2, PGF2alpha and 8-isoprostane F2alpha but reduced the
      concomitant formation of PGI2. These data demonstrate that LPS and cytokines
      influence the relative balance of TXA2, PGI2, PGF2alpha and 8-isoprostane F2alpha
      in pig PA, which in turn alter NADPH oxidase expression and O2*- formation. These
      novel findings have implications in devising effective strategies for treating
      ARDS.British Journal of Pharmacology (2004) 141, 488-496.
      doi:10.1038/sj.bjp.0705626

PMID- 14718264
TI  - Role of PKC in the attenuation of the cGMP-mediated relaxation of skinned
      resistance artery smooth muscle seen in glyceryl-trinitrate-tolerant rabbit.
AB  - We examined whether 10 days' in vivo treatment with glyceryl trinitrate (GTN)
      might reduce cGMP-induced relaxation in the smooth muscle of rabbit mesenteric
      resistance arteries and, if so, whether protein kinase C (PKC) plays a role in
      this downregulation. The relaxation responses to GTN and the nitric oxide donor
      NOC-7 were significantly reduced in endothelium-denuded strips from GTN-treated
      rabbits. In beta-escin-skinned smooth muscle, the ability of 8-bromoguanosine
      3',5' cyclic monophosphate (8-Br-cGMP, a phosphodiesterase-resistant cGMP
      analogue) to relax the contraction induced by 0.3 microM Ca2+ was significantly
      reduced in GTN-treated rabbits. In beta-escin-skinned smooth muscle, an inhibitor
      of conventional and/or novel PKCs, GF109203X (0.6 microM), inhibited the Ca2+ 
      induced contraction and enhanced the 8-Br-cGMP-induced relaxation. However, since
      the relaxing ability of 8-Br-cGMP was found to be unchanged by GF109203X when
      contractions were amplitude-matched (0.2 microM Ca2+ alone vs 0.3 microm Ca2+ +
      GF109203X), the increase in the 8-Br-cGMP-response seen with GF109203X was
      probably due to its inhibitory action on the Ca2+ -induced contraction.
      Furthermore, although the PKC activator phorbol 12,13-dibutyrate (PDBu, 0.1
      microM) decreased the 8-Br-cGMP-induced relaxation of the Ca2+ (0.3 microM)
      contraction, this was probably due to its enhancement of the Ca2+ -induced
      contraction since no such effect of PDBu was seen when the Ca2+ -induced
      contractions were amplitude-matched (0.2 microM Ca2+ + PDBu vs 0.3 microM Ca2+
      alone). These results suggest that the relaxing response to cGMP is reduced in
      the smooth muscle of mesenteric resistance arteries in GTN-treated rabbits but
      that conventional and/or novel PKCs do not play a major role in maintaining this
      downregulation. British Journal of Pharmacology (2004) 141, 391-398.
      doi:10.1038/sj.bjp.0705625

PMID- 14718265
TI  - Calcitonin gene-related peptide facilitates serotonin release from guinea-pig
      colonic mucosa via myenteric neurons and tachykinin NK2/NK3 receptors.
AB  - The ability of calcitonin gene-related peptide (CGRP), to alter the outflow of 5
      hydroxytryptamine (5-HT) from the guinea-pig proximal colon, was evaluated using
      three different isolated preparations: whole colon, mucosa-free muscle layer and
      submucosa/mucosa preparations. In the presence of the monoamine oxidase A
      inhibitor, clorgyline, CGRP elicited a concentration-dependent increase in 5-HT
      outflow from the whole colon, but not from mucosa-free muscle layer preparations.
      The CGRP-evoked 5-HT outflow was sensitive to tetrodotoxin (TTX) or
      hexamethonium, but was not detectable in submucosa/mucosa preparations. HCGRP8-37
      (3 microM) inhibited the submaximal effect of CGRP on the 5-HT outflow.
      [Cys(ACM)2,7]hCGRP had a slight stimulant influence on the 5-HT outflow. The
      selective NK2 and NK3 receptor antagonists, SR48968 or SR142801, respectively,
      prevented the enhancing effect of CGRP. By contrast, a selective NK1 receptor
      antagonist L703606, failed to block the effect of CGRP. The enhancing effect of
      CGRP was mimicked by the NK2 receptor agonist [beta-Ala8]-neurokinin A (NKA)4-10
      and the NK3 receptor agonist senktide. The effect of [beta-Ala8]-NKA4-10 on the 5
      HT outflow was unaffected by TTX, while the effect of senktide was prevented by
      TTX, hexamethonium or SR48968. The present data also demonstrated a synergistic
      action of the NK2 and NK3 receptor agonists on the CGRP-evoked 5-HT outflow. We
      concluded that CGRP facilitates 5-HT release from the guinea-pig colonic mucosa
      through an action on myenteric neurons and that this effect is mediated by
      endogenously released tachykinins, acting via tachykinin NK2/NK3 receptors in
      cascade. British Journal of Pharmacology (2004) 141, 385-390.
      doi:10.1038/sj.bjp.0705624

PMID- 14718267
TI  - Seattle's Harborview Medical Center, 1877-2003.

PMID- 14718266
TI  - Specialist nurse intervention to reduce unscheduled asthma care in a deprived
      multiethnic area: the east London randomised controlled trial for high risk
      asthma (ELECTRA).
AB  - OBJECTIVE: To determine whether asthma specialist nurses, using a liaison model
      of care, reduce unscheduled care in a deprived multiethnic area. DESIGN: Cluster
      randomised controlled trial. SETTING: 44 general practices in two boroughs in
      east London. PARTICIPANTS: 324 people aged 4-60 years admitted to or attending
      hospital or the general practitioner out of hours service with acute asthma; 164
      (50%) were South Asian patients, 108 (34%) were white patients, and 52 (16%) were
      from other, largely African and Afro-Caribbean, ethnicities. INTERVENTION:
      Patient review in a nurse led clinic and liaison with general practitioners and
      practice nurses comprising educational outreach, promotion of guidelines for high
      risk asthma, and ongoing clinical support. Control practices received a visit
      promoting standard asthma guidelines; control patients were checked for inhaler
      technique. MAIN OUTCOME MEASURES: Percentage of participants receiving
      unscheduled care for acute asthma over one year and time to first unscheduled
      attendance. RESULTS: Primary outcome data were available for 319 of 324 (98%)
      participants. Intervention delayed time to first attendance with acute asthma
      (hazard ratio 0.73, 95% confidence interval 0.54 to 1.00; median 194 days for
      intervention and 126 days for control) and reduced the percentage of participants
      attending with acute asthma (58% (101/174) v 68% (99/145); odds ratio 0.62, 0.38
      to 1.01). In analyses of prespecified subgroups the difference in effect on
      ethnic groups was not significant, but results were consistent with greater
      benefit for white patients than for South Asian patients or those from other
      ethnic groups. CONCLUSION: Asthma specialist nurses using a liaison model of care
      reduced unscheduled care for asthma in a deprived multiethnic health district.
      Ethnic groups may not benefit equally from specialist nurse intervention.

PMID- 14718268
TI  - Completion pancreatectomy for postoperative peritonitis after
      pancreaticoduodenectomy: early and late outcome.
AB  - HYPOTHESIS: Completion pancreatectomy in patients with pancreatic leakage
      associated with postoperative peritonitis after pancreaticoduodenectomy is a
      viable salvage procedure. DESIGN: Retrospective analysis from a cohort of
      consecutive patients admitted between January 1, 1989, and December 31, 1999, for
      postoperative peritonitis originating from pancreaticojejunostomy leakage.
      SETTING: Tertiary referral center with surgical intensive care unit specializing
      in the treatment of intra-abdominal sepsis. PATIENTS: Eight consecutive patients
      with postoperative peritonitis originating from pancreaticojejunostomy after
      pancreaticoduodenectomy, with a mean Acute Physiology and Chronic Health
      Evaluation II score of 18.6. We excluded patients with pancreatic fistulas or
      abscesses amenable to percutaneous drainage or other conservative treatment.
      INTERVENTION: Completion pancreatectomy. MAIN OUTCOME MEASURES: Mortality,
      morbidity, and long-term outcome, which was assessed by interview. RESULTS: Three
      patients died in the postoperative period: 2 required early reoperation during
      the postoperative period and died of hemorrhage and sepsis, and 1 died of
      multiorgan failure without reoperation. Recurrence of carcinoma was responsible
      for late death of 2 other patients. CONCLUSIONS: Postoperative peritonitis after
      pancreaticoduodenectomy still has high mortality; however, completion
      pancreatectomy may represent the only means to achieve source control of
      infection in cases of postoperative peritonitis.

PMID- 14718269
TI  - Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal
      carcinomatosis arising from gastric cancer.
AB  - HYPOTHESIS: The most common cause of palliative resection and recurrence in
      gastric cancer is peritoneal seeding. This study evaluates the efficacy of
      intraperitoneal chemohyperthermia after cytoreductive surgery in patients with
      peritoneal carcinomatosis arising from gastric cancer. DESIGN: Prospective
      clinical trial. SETTING: Surgical department at a university academic hospital.
      PATIENTS: Forty-nine consecutive patients with peritoneal carcinomatosis treated
      between January 1, 1989, and February 29, 2000. INTERVENTIONS: All patients
      underwent intraperitoneal chemohyperthermia with mitomycin C (40-60 mg); 21
      patients had previously undergone extensive cytoreductive surgery. MAIN OUTCOME
      MEASURES: Clinicopathologic factors that affect overall survival rates. RESULTS:
      With median follow-up of 99 months, overall median survival was 10.3 months. Two
      factors were significant independent predictors of survival by multivariate
      analysis: preoperative ascites (P =.04) and completeness of cancer resection
      (CCR) by cytoreductive surgery (P<.001). Median survival was 21.3 months for
      patients with CCR-0 (macroscopic complete resection) or CCR-1 (diameter of
      residual nodules <5 mm) and 6.1 months for patients with CCR-2 (diameter of
      residual nodules >5 mm) (P<.001). Four patients survived longer than 5 years.
      CONCLUSIONS: An aggressive management strategy combining intraperitoneal
      chemohyperthermia with cytoreductive surgery is effective for patients with
      peritoneal carcinomatosis arising from gastric cancer. In highly selected
      patients (good general status, resectable primary tumor, resectable peritoneal
      carcinomatosis), this therapy may result in long-term survival.

PMID- 14718270
TI  - Clinical characteristics of breast cancer patients in Korea in 2000.
AB  - HYPOTHESIS: Breast cancer in Korea continues to rise year by year, and its
      clinical features will become closer to those now observed in Western countries.
      DESIGN: Nationwide multicenter survey of the Korean Breast Cancer Society in
      2000. PARTICIPANTS: A total of 5401 patients (median age, 46 years) with newly
      diagnosed breast cancer who underwent surgery at 38 university and 45 surgical
      training hospitals. MAIN OUTCOME MEASURES: All participating hospitals provided
      the essential data, including sex, age, the surgical method used, and the
      American Joint Committee on Cancer classification to determine the clinical
      characteristics of breast cancer and to compare the results with those of
      previous surveys conducted in 1996 and 1998 to obtain an epidemiological pattern
      of breast cancer in Korea. RESULTS: An estimated crude incidence was 23/100 000
      patients. Premenopausal women younger than 50 years constituted 61.2%. Of the
      study population, 71.5%underwent mastectomy; 27.1%, breast-conserving surgery;
      and 1.4%, other surgical treatments. In all, 52.8% were diagnosed as having stage
      II disease (American Joint Committee on Cancer classification), and the
      proportion of early cancer (stages 0 and I) was 31.5%. Comparisons with 1996 and
      1998 results indicated that the number of patients with breast cancer is
      increasing. Mastectomies occurred less frequently and breast-conserving surgery
      more frequently (P<.001), and we noted an increase in the proportion of early
      cancer (P<.001). The number of patients with risk factors such as early menarche
      (P =.003), late menopause (P =.01), a high-fat diet (P =.048), and familial
      history of breast cancer (P =.046) was also found to have significantly
      increased. CONCLUSIONS: Although our epidemiological survey was limited in terms
      of its duration, our findings suggest that the incidence of breast cancer in
      Korea will continue to rise and that the clinical features will become closer to
      those now observed in Western countries.

PMID- 14718272
TI  - Breast conservation surgery using nipple-areolar resection for central breast
      cancers.
AB  - HYPOTHESIS: Resection of the nipple-areolar complex (NAC) for central breast
      cancers that involve the nipple or areola, with postoperative radiation therapy,
      adheres to the oncologic principles established for breast conservation surgery
      of other breast cancers. Good or excellent cosmetic results can be achieved. The
      rate of ipsilateral breast recurrence will be similar to that seen with
      peripheral breast cancers. The indications for breast conservation surgery can be
      safely extended to include patients with breast cancers that involve the NAC.
      DESIGN: Retrospective medical record review; follow-up patient questionnaire.
      SETTING: Community teaching hospital. PATIENTS: Fifteen patients, aged 46 to 88
      years, whose central breast cancers involved the NAC precluding preservation of
      the NAC. INTERVENTIONS: Nipple-areolar complex resection, postoperative radiation
      therapy. MAIN OUTCOME MEASURES: Ipsilateral breast recurrence, survival,
      cosmesis. RESULTS: Ten patients had subareolar cancers that directly involved the
      nipple or areola; 5 patients had Paget disease of the nipple. Average tumor size
      was 1.6 cm (range, 0.2-3.5 cm). With a mean follow-up of 32 months (range, 4-109
      months), there has been only 1 recurrence (7%), which was treated successfully by
      modified radical mastectomy. All 15 patients are alive and free of disease.
      Cosmetic results are satisfactory to excellent, as judged by both the patients
      and the surgeons. CONCLUSIONS: Nipple-areolar complex resection for central
      subareolar cancers that directly involve the NAC, as well as for Paget disease of
      the nipple, extends the indications for breast conservation in other areas of the
      breast, and with acceptable cosmesis.

PMID- 14718273
TI  - Operative blood loss and use of blood products after laparoscopic and
      conventional open colorectal operations.
AB  - HYPOTHESIS: Blood loss, measured by estimated blood loss, drop in hemoglobin
      levels, and transfusion requirements, is lower in patients undergoing
      laparoscopic colectomy compared with patients undergoing conventional open
      colectomy. DESIGN: Case-matched study. SETTING: A university hospital. PATIENTS:
      Patients undergoing laparoscopic colectomy between January 2000 and December 2001
      were matched in a prospective database for age, sex, comorbidity, and surgical
      procedure with patients undergoing open colectomy during the same period. MAIN
      OUTCOME MEASURES: Estimated blood loss, drop in hemoglobin levels, and
      transfusion requirements after surgery were compared. RESULTS: One hundred forty
      seven patients undergoing the same operation using either an open or laparoscopic
      approach could be matched for age, sex, and diagnosis related grouping. There was
      no significant difference in American Society of Anesthesiologists class, body
      mass index, or preoperative and postoperative hemoglobin levels, but the open
      colectomy group required significantly more units of blood (P =.003) to maintain
      similar hemoglobin levels after surgery. Estimated blood loss (P<.001) and the
      number of patients who received transfusions on the day of surgery (P =.002),
      during the first 48 hours after surgery (P =.005), and during the entire hospital
      stay (P =.003) were significantly higher in the open colectomy group. CONCLUSION:
      A laparoscopic approach for colorectal surgery led to significantly less blood
      loss than matched open colectomy cases.

PMID- 14718274
TI  - Skip metastases in thyroid cancer leaping the central lymph node compartment.
AB  - HYPOTHESIS: Discontinuous nodal metastasis, or skip metastasis, in thyroid cancer
      may display clinicopathologic features different from those seen in continuous
      nodal metastasis and thus may have a different prognosis. DESIGN: Retrospective
      analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS:
      Two hundred fifteen consecutive patients who underwent systematic central lymph
      node dissection for papillary, follicular, or medullary thyroid cancer and who on
      histopathologic analysis exhibited nodal metastases in at least 1 lateral or
      mediastinal lymph node compartment. MAIN OUTCOME MEASURES: Various
      clinicopathologic variables that were stratified for tumor entity and type of
      nodal metastasis (discontinuous vs continuous). RESULTS: Skip metastases
      (negative central and positive lateral or mediastinal compartments) were found in
      13 (19.7%) of 66 papillary, 0 of 8 follicular, and 30 (21.3%) of 141 medullary
      thyroid cancers. After adjustment for multiple testing, skip metastasis was only
      associated with significantly fewer positive lymph nodes: 3.7 vs 12.9 nodes (r = 
      0.43, P<.001) in papillary thyroid cancer and 6.0 vs 17.1 nodes (r = -0.40,
      P<.001) in medullary thyroid cancer. No other significant correlation was
      identified with any other clinicopathologic variable. CONCLUSIONS: Skip
      metastasis is an epiphenomenon of low-intensity nodal metastasis in thyroid
      cancer and entails a moderate risk of local recurrence. Consequently, clearing
      the central lymph node compartment should be considered when lateral or
      mediastinal lymph node compartments are involved.

PMID- 14718275
TI  - Applicability of laparoscopic adrenalectomy in a prospective study in 150
      consecutive patients.
AB  - HYPOTHESIS: Within a decade, laparascopic adrenalectomy has become the new "gold
      standard" for the surgical treatment of most adrenal lesions. Designed as a
      single-center project focused on patients with adrenal lesions, this study should
      provide an indication of the number of patients requiring surgery who can safely
      undergo laparoscopy, after consideration of such selection criteria as tumor size
      and benign or malignant lesion status at magnetic resonance imaging. Furthermore,
      the access-related complications were analyzed. DESIGN: According to a
      prospective protocol, 150 consecutive patients selected for adrenal surgery were
      assigned to transperitoneal endoscopic or open adrenalectomy. SETTING: University
      hospital section of endocrine surgery. RESULTS: One hundred two patients (68%)
      were selected for a laparoscopic approach that had to be converted to open
      surgery in 5 patients (5%). Two malignant cortisol-secreting lesions were
      operated on laparoscopically because of their small size and benign appearance at
      magnetic resonance imaging. During histological examination, 14 (29%) of 48
      patients assigned to transperitoneal open adrenalectomy had lesions deemed
      malignant (16 [11%] of 150 patients). The laparoscopic group had significantly
      fewer complications (9%) than did the open group (21%; P =.04). CONCLUSIONS: By
      applying defined selection criteria for the treatment of adrenal lesions,
      transperitoneal endoscopic adrenalectomy can be a safe procedure and may be
      performed in at least two thirds of patients. The choice of endoscopic or open
      approach in larger tumors should depend on the results of preoperative imaging
      studies and the endocrine surgeon's experience in endoscopic adrenal surgery.

PMID- 14718276
TI  - Estrogen and androgen receptors as comediators of breast cancer cell
      proliferation: providing a new therapeutic tool.
AB  - HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) comediates breast cancer
      progression via estrogen receptors (ERs) and androgen receptors (ARs). DESIGN:
      Breast cancer cells that were ER positive-AR positive or ER negative-AR positive
      were pretreated with anastrozole, tamoxifen citrate, or bicalutamide, then
      stimulated with 228 microM DHEA-S. SETTING: University Surgical Oncology Research
      Laboratory. MAIN OUTCOME MEASURES: Receptor status was confirmed by reverse
      transcriptase polymerase chain reaction. Cellular activity was measured by a
      methylthiotetrazole proliferation assay in addition to ER nuclear translocation
      and mitogen-activated protein kinase activity by immunoassays. RESULTS: The use
      of DHEA-S induced growth of 43.4% in ER-positive-AR-positive cells but inhibited
      ER-negative-AR-positive cells by 22%. Tamoxifen reduced growth of ER-positive-AR
      positive cells to 8.9%. Bicalutamide restored normal growth of ER-negative-AR
      positive cells. The ER nuclear translocation rate of 51% was reduced to 11% with
      tamoxifen. The use of DHEA-S induced mitogen-activated protein kinase by 5.4
      fold. CONCLUSIONS: Stimulation with DHEA-S induced proliferation through the ER
      but inhibited cells via the AR. Therapeutic comediation of receptors may provide
      effective treatment for ER-negative-AR-positive breast cancers.

PMID- 14718277
TI  - Oxygen transport dynamics after resuscitation with a conjugated hemoglobin
      solution.
AB  - HYPOTHESIS: Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a
      hemoglobin-based oxygen carrier, is effective in restoring hemodynamic balance
      and oxygen delivery after moderate hemorrhage but may be less effective in off
      loading oxygen at the tissue level. DESIGN: Before-after trial. SETTING: Animal
      research laboratory of an academic institution. PARTICIPANTS: Ten female
      Yorkshire swine. INTERVENTIONS: Anesthetized swine underwent a 25% controlled
      hemorrhage followed by resuscitation with crystalloid plus either shed blood or
      PHP. Hemodynamic parameters, including heart rate, mean arterial pressure, mean
      pulmonary arterial pressure, and cardiac index were continuously monitored.
      Arterial and mixed venous blood samples were collected at baseline, after
      hemorrhage, after resuscitation, and every 15 minutes for 90 minutes after
      resuscitation. Oxygen delivery and consumption, oxygen extraction ratios, and
      percentage of contribution to oxygen delivery and consumption were determined in
      whole blood, red blood cells, and plasma by using a compartmentalized approach.
      MAIN OUTCOME MEASURES: Intergroup and intragroup comparisons were performed for
      hemodynamic parameters and oxygen transport dynamics. RESULTS: Heart rate
      returned closer to baseline levels in the PHP group (P<.05) and mean pulmonary
      arterial pressure was transiently elevated after infusion of PHP (P =.028), but
      otherwise no significant differences in hemodynamic balance were observed. The
      extraction ratio from the red blood cells in the PHP group more than doubled,
      whereas the extraction ratio from plasma remained constant. The percentage of
      contribution of plasma, including PHP, to oxygen delivery exceeded 20% (P <.05),
      but the relative contribution to oxygen consumption did not markedly change from
      baseline. CONCLUSIONS: Pyridoxalated hemoglobin polyoxyethylene conjugate is at
      least as effective as shed blood in restoring hemodynamic balance and oxygen
      delivery after moderate hemorrhage. There is a disproportionately low
      contribution from plasma to oxygen consumption, which suggests that PHP may act
      as an oxygen sink in moderate anemia.

PMID- 14718278
TI  - Predictive factors for successful laparoscopic splenectomy in patients with
      immune thrombocytopenic purpura.
AB  - HYPOTHESIS: Younger patients with immune thrombocytopenic purpura (ITP) and high
      preoperative platelet counts successfully respond to laparoscopic splenectomy
      (LS). DESIGN: Case series. SETTING: Private, tertiary care referral center.
      PATIENTS: Sixty-seven consecutive patients undergoing LS for ITP between 1995 and
      2001. INTERVENTIONS: Laparoscopic splenectomy. MAIN OUTCOME MEASURES: A
      successful response to LS was defined as a postoperative platelet count greater
      than 100 x 10(3)/microL without medical therapy. Failures were classified as
      recurrent or refractory. Patients considered refractory to surgery did not
      achieve a platelet count greater than 100 x 10(3)/microL without medical therapy.
      Patients with recurrent ITP initially achieved a platelet count greater than 100
      x 10(3)/microL, but thrombocytopenia subsequently recurred. RESULTS: Both
      univariate and multivariate analyses were performed for 13 preoperative variables
      to identify factors predictive of success following LS. At a mean follow up of 22
      months, 43 patients (64%) had a successful response to LS, 14 (21%) were
      refractory, and 10 (15%) developed recurrent ITP. By univariate analysis,
      patients responding to laparoscopic splenectomy were younger (P =.005) and had a
      higher preoperative platelet count (P =.005). In multivariate analysis, younger
      age (P =.005) and a higher preoperative platelet count (P =.007) again predicted
      a successful response to LS. CONCLUSIONS: A successful response to LS for ITP is
      expected in patients younger than 50 years and in those with preoperative
      platelet counts greater than 70 x 10(3)/microL. These factors can be incorporated
      into an equation that yields a splenectomy prediction score, which predicts the
      success of LS for ITP.

PMID- 14718279
TI  - Inpatient hospital admission and death after outpatient surgery in elderly
      patients: importance of patient and system characteristics and location of care.
AB  - HYPOTHESIS: Surgery at different outpatient care locations in the higher-risk
      elderly (age >65 years) population is associated with similar rates of inpatient
      hospital admission and death. DESIGN: Claims analysis of patients undergoing 16
      different surgical procedures in a nationally representative (5%) sample of
      Medicare beneficiaries for the years 1994 through 1999. SETTING: Hospital-based
      outpatient centers, freestanding ambulatory surgery centers (ASCs), and
      physicians' office facilities. PATIENTS: Medicare beneficiaries older than 65
      years. MAIN OUTCOME MEASURES: Rate of death, emergency department risk, and
      admission to an inpatient hospital within 7 days of outpatient surgery. RESULTS:
      We studied 564,267 outpatient surgical procedures: 360,780 at an outpatient
      hospital, 175,288 at an ASC, and 28,199 at a physician's office. There were no
      deaths the day of surgery at a physician's office, 4 deaths the day of surgery at
      an ASC (2.3 per 100,000 outpatient procedures), and 9 deaths the day of surgery
      at an outpatient hospital (2.5 per 100,000 outpatient procedures). The 7-day
      mortality rate was 35 per 100,000 outpatient procedures at a physician's office,
      25 per 100,000 outpatient procedures at an ASC, and 50 per 100,000 outpatient
      procedures at an outpatient hospital. The rate of admission to an inpatient
      hospital within 7 days of outpatient surgery was 9.08 per 1000 outpatient
      procedures at a physician's office, 8.41 per 1000 outpatient procedures at an
      ASC, and 21 per 1000 outpatient procedures at an outpatient hospital. In
      multivariate models, more advanced age, prior inpatient hospital admission within
      6 months, surgical performance at a physician's office or outpatient hospital,
      and invasiveness of surgery identified those patients who were at increased risk
      of inpatient hospital admission or death within 7 days of surgery at an
      outpatient facility. CONCLUSION: This study represents an initial effort to
      demonstrate the risk associated with outpatient surgery in a large, diverse
      population of elderly individuals.

PMID- 14718280
TI  - Postoperative rhabdomyolysis following laparoscopic gastric bypass in the
      morbidly obese.
AB  - HYPOTHESIS: Laparoscopic approaches for weight reduction in the morbidly obese
      have become common with more than 50,000 bariatric surgical procedures being
      performed in 2001. The objective of this article is to raise awareness among
      surgeons of a new complication of rhabdomyolysis from this frequent procedure.
      DESIGN: Case series extracted from surgical database from January 2, 2001,
      through December 31, 2002. PATIENTS AND METHODS: We identified 5 cases of
      postoperative rhabdomyolysis in morbidly obese patients who underwent
      laparoscopic duodenal switch procedures with parietal gastrectomy. The cause,
      pathogenesis, and clinical features are reviewed and discussed. RESULTS:
      Postoperative rhabdomyolysis developed in 5 of 353 morbidly obese patients who
      underwent consecutive laparoscopic duodenal switch procedures, an incidence of
      1.4%. All 5 patients were male, had a mean peak serum creatine kinase level of 19
      680 U/L, and reported muscle pain in either the buttock, hip, or shoulder regions
      during the early postoperative period. CONCLUSIONS: We hypothesized that morbidly
      obese patients develop critical surface and deep tissue pressures during
      bariatric surgery, increasing their risk for tissue injury and rhabdomyolysis.
      Unexplained elevations in the serum creatinine level or reports of buttock, hip,
      or shoulder pain in the postoperative period should raise the possibility of
      rhabdomyolysis and prompt clinical investigation. We recommend routine
      preoperative and postoperative measurements of the serum creatine kinase and
      serum creatinine levels to aid detection. Surgeons need to keep a low index of
      suspicion because early diagnosis and treatment are the cornerstones of
      successful management of rhabdomyolysis.

PMID- 14718281
TI  - Surgical treatment for primary hyperparathyroidism in Hong Kong: changes in
      clinical pattern over 3 decades.
AB  - HYPOTHESIS: With the introduction of the blood chemistry multichannel
      autoanalyzer, primary hyperparathyroidism (HPT) is increasingly diagnosed. The
      clinical pattern of primary HPT has undergone a significant evolution in Western
      countries. A similar change can be documented in a geographic region where this
      condition is considered to be relatively uncommon. DESIGN: Unselected case
      series. SETTING: A tertiary referral endocrine surgical unit. PATIENTS: All
      patients with primary HPT surgically treated over the past 30 years. MAIN OUTCOME
      MEASURES: The prevalence of patients per 100,000 hospital admissions, clinical
      presentation, biochemistry study results, pathologic status, and main outcome
      were compared over three 10-year spans according to the introduction of the
      multichannel autoanalyzer in 1982: 1973-1982 (n = 20), 1983-1992 (n = 31), and
      1993-2002 (n = 190). RESULTS: A 7-fold increase in the prevalence of patients
      with primary HPT who were surgically treated per 100,000 hospital admissions was
      observed over the past 10 years. The clinical presentation of patients with
      primary HPT had evolved progressively with a higher proportion of older patients
      (P<.001) being asymptomatic. On presentation, the condition had decreased in
      severity with lower serum calcium (P =.04), parathyroid hormone (P<.001), and
      alkaline phosphatase levels (P<.001) as well as a smaller adenoma size (P<.001).
      There was no significant change in the underlying pathologic condition and
      surgical success. CONCLUSION: Similar to the West but in contrast to that
      observed in other Asian countries, an increase in the prevalence of patients
      surgically treated for primary HPT is documented and a change in disease
      presentation as well as its severity is observed in our population group.

PMID- 14718282
TI  - Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological
      samples for differentiating follicular thyroid carcinoma from follicular adenoma.
AB  - HYPOTHESIS: Dipeptidyl aminopeptidase IV (DPP IV) activity in cytological samples
      from a follicular thyroid tumor is the most sensitive and specific indicator for
      the detection of follicular carcinoma of the thyroid gland. Dipeptidyl
      aminopeptidase IV activity is independent of cytological characteristics and
      superior to other clinical findings. DESIGN AND PATIENT SELECTION: Among the
      patients surgically treated for follicular thyroid tumors, we recruited
      approximately equal numbers of those with true-positive (n = 19), true-negative
      (n = 26), false-negative (n = 16), and false-positive (n = 18) cytological
      characteristics. MAIN OUTCOME MEASURES: We examined DPP IV activity using
      cytological specimens obtained from 35 patients with follicular thyroid
      carcinomas and 44 patients with follicular adenomas. Tumor size, patient age,
      serum thyroglobulin level, and ultrasonographic findings were also analyzed.
      RESULTS: The positive rate of DPP IV activity was 97% in 35 patients with
      follicular thyroid carcinomas and 5% in 44 patients with follicular adenomas,
      resulting in a sensitivity of 97%, a specificity of 95%, and an overall accuracy
      of 96%. This discriminating ability of DPP IV activity was far higher than that
      of tumor size, patient age, serum thyroglobulin level, or ultrasonographic
      findings. CONCLUSIONS: Positive DPP IV activity in cytological samples is the
      best discriminatory marker between follicular thyroid carcinoma and follicular
      adenoma. Its application could alter the clinical management of patients with
      follicular thyroid tumors.

PMID- 14718283
TI  - Optimal angle between instrument shaft and handle for laparoscopic bowel
      suturing.
AB  - OBJECTIVE: To determine the optimal angle between the handle and instrument shaft
      for endoscopic suturing. DESIGN: A rocker handle needle driver was used to
      investigate the 0 degrees, 40 degrees, and 80 degrees handle-to-shaft angles. The
      standard task entailed closure of a 50-mm enterotomy in a nonliving porcine small
      bowel model. Fifty enterotomies were performed with each angle in a random
      sequence. SETTING: Research laboratory in the Surgical Skills Unit at Ninewells
      Hospital. PARTICIPANTS: Ten surgeons with previous experience in laparoscopic
      surgery. MAIN OUTCOME MEASURES: The execution time (in minutes), leakage pressure
      (in centimeters of water), and suture error placement score (deviations of the
      entry and exit points <3 mm or >5 mm from the enterotomy edge or between
      sutures). RESULTS: The 40 degrees handle-to-shaft angle had a higher mean (SD)
      leakage pressure of 43.8 (20.0) cm H2O compared with the 80 degrees and 0 degrees
      angles (31.1 [21.0] and 26.3 [19.0] cm H2O, respectively) (P<.001). In addition,
      the 40 degrees angle had a lower mean (SD) suture error placement score of 13.6
      (7.6), compared with the 80 degrees and 0 degrees angles (19.4 [9.4] and 21.1
      [8.5], respectively) (P<.001). No significant difference was found in the
      execution time between the different angles (P =.20). CONCLUSION: The best
      quality of laparoscopic bowel suturing, in terms of the accuracy of suture
      placement and the integrity of the suture line closure, was obtained with a 40
      degrees handle-to-shaft angle.

PMID- 14718284
TI  - Stem cells: review and update.
AB  - Regenerative medicine and emerging biotechnologies stand to revolutionize the
      practice of medicine. Advancements in stem cell biology, including embryonic and
      postnatal somatic stem cells, have made the prospect of tissue regeneration a
      potential clinical reality. Short of reproductive cloning, these same
      technologies, properly used, could allow for the creation of replacement tissue
      for the deficient host. To provide a concise review for surgeons on the current
      science and biology of stem cells, we surveyed the scientific literature,
      MEDLINE, and relevant political headlines that illuminate the stem cell
      discussion; the issues are summarized in this review. Building on this conceptual
      framework, the related issues of clinical promise and the political debate
      enveloping this emerging technology are examined. A basic understanding of stem
      cell biology is paramount to stay informed of this emerging technology and the
      national debate.

PMID- 14718285
TI  - Surgery in Sweden at the time of Halsted.
AB  - William Stewart Halsted (1852-1922) is one of the most influential persons in the
      history of US surgery. His surgical career can be divided into the years in New
      York, NY (1880-1889), and the years in Baltimore, Md (1889-1922). In addition to
      the important growth and development of surgery that took place in the United
      States during the late 1800s and early 1900s, an equally impressive growth in
      surgery took place in many other countries, in particular, in Western Europe.
      Although a small country, Sweden also saw a strong development of surgery between
      1880 and 1920. In this article, some of the surgeons who were prominent in Sweden
      during this era (Karl Gustav Lennander in Uppsala; John Wilhelm Berg in
      Stockholm; and Jacques Borelius in Lund) and some of the surgical procedures that
      were introduced are described. In addition, a few nonsurgeons are discussed
      because their work significantly influenced surgery. Learning about some of the
      achievements in surgery during the late 1800s and early 1900s is not only
      educational but inspiring, and puts today's surgical practice and scientific
      achievements in an important historical perspective.

PMID- 14718286
TI  - Image of the month. Focal nodular hyperplasia.

PMID- 14718288
TI  - A randomized prospective clinical trial comparing laser subepithelial
      keratomileusis and photorefractive keratectomy.
AB  - OBJECTIVE: To compare laser subepithelial keratomileusis (LASEK) and
      photorefractive keratectomy (PRK) in different eyes of the same subjects for
      subjective pain level, visual acuity, and corneal epithelial healing. DESIGN:
      Prospective, randomized, double-masked study. SETTING: David Grant US Air Force
      Medical Center, Travis Air Force Base, Calif. PARTICIPANTS: A convenience sample
      of 30 active-duty military members with mild to moderate myopia. METHODS: All
      patients had LASEK performed in one eye and PRK performed in the contralateral
      eye; the order of surgical procedures (ie, right eye first or left eye first) and
      the choice of procedures (ie, PRK in the right eye and LASEK in the left eye or
      LASEK in the right eye and PRK in the left eye) were determined in advance using
      a block randomization table. MAIN OUTCOME MEASURES: The primary outcome measures
      were subjective pain level and the rate of corneal epithelial defect recovery.
      Postoperatively, subjects were evaluated for their subjective pain level, visual
      acuity, and corneal healing (ie, epithelial defect size) during the first week
      and up to 30 days after undergoing the surgical procedures. RESULTS: There were
      no significant differences in subjective pain levels between the LASEK- and PRK
      treated eyes on postoperative days 1, 2, or 3 (P>.05) or in visual acuity on
      postoperative days 3, 7, or 30 (P>.05). There was a statistically significant
      (P<.001) smaller median epithelial defect in the LASEK-treated group (1.0 mm(2))
      compared with the PRK-treated group (16.0 mm(2)) on postoperative day 1. However,
      by postoperative day 3, the PRK-treated group (0.0 mm(2)) showed significantly
      (P<.001) smaller epithelial defects compared with the LASEK-treated group (4.0
      mm(2)). By postoperative day 7, epithelial defects were undetectable in any
      subjects in either group. CONCLUSIONS: Laser subepithelial keratomileusis and PRK
      have similar postoperative pain thresholds and visual acuity recordings. However,
      the epithelial healing pattern for LASEK and PRK differs. No additional clinical
      benefit is seen from the LASEK procedure relative to the PRK procedure.

PMID- 14718289
TI  - Central corneal thickness as a risk factor for advanced glaucoma damage.
AB  - OBJECTIVE: To determine if central corneal thickness (CCT) is related to the
      level of glaucoma severity at the initial examination. METHODS: The initial visit
      to a glaucoma specialist by consecutive patients with primary open-angle glaucoma
      from 1997 to 2002 was reviewed retrospectively. Each patient's age, sex, race,
      family history of glaucoma, number of glaucoma medications, visual acuity,
      spherical equivalent, intraocular pressure, CCT, visual field data, and vertical
      and horizontal cup-disc ratios were analyzed. RESULTS: Three hundred fifty eyes
      of 190 patients met the inclusion and exclusion criteria. Central corneal
      thickness was significantly lower in blacks (mean, 537 microm) than in whites
      (mean, 556 microm). Lower CCT was significantly associated with worsened Advanced
      Glaucoma Intervention Study score, worsened mean deviation of visual field,
      increased vertical and horizontal cup-disc ratios, and increased number of
      glaucoma medications. In multivariate analysis, lower CCT was significantly
      associated with worsened Advanced Glaucoma Intervention Study score, worsened
      mean deviation of visual field, and increased vertical and horizontal cup-disc
      ratios. CONCLUSIONS: Central corneal thickness is a powerful clinical factor in
      determining glaucoma severity at the initial examination by a specialist.
      Measuring CCT may aid the ophthalmologist in identification of glaucoma patients
      at high risk for progression.

PMID- 14718290
TI  - Racial differences in optic disc topography: baseline results from the confocal
      scanning laser ophthalmoscopy ancillary study to the ocular hypertension
      treatment study.
AB  - OBJECTIVE: To examine racial differences in optic disc topography among ocular
      hypertensive participants in the Ocular Hypertension Treatment Study. METHODS:
      Four hundred thirty-nine participants from 7 Ocular Hypertension Treatment Study
      centers who had good-quality baseline images obtained using a quantitative 3
      dimensional confocal scanning laser ophthalmoscope, the Heidelberg Retina
      Tomograph (Heidelberg Engineering, Dossenheim, Germany), were included in this
      study. The first 10 degrees- or 15 degrees-field of view mean topographic image
      acquired was included in all analyses. Differences in Heidelberg Retina Tomograph
      topographic optic disc parameter measurements by self-identified race were
      assessed using a mixed-effects linear model to control for confounders and for
      the use of both eyes in the model. RESULTS: By self-attribution, 74 (17%) of the
      439 participants were of African origin, 329 (75%) were white, 24 (5%) were
      Hispanic, and 12 (3%) were Native American, Native Alaskan, Asian, Pacific
      Islander, or unknown. The African American participants had statistically
      significantly (P<.001) larger mean (SD) optic disc areas than the other
      participants, 2.17 (0.41) mm(2) vs 1.87 (0.38) mm(2), respectively. African
      American participants had a larger cup area, cup volume, cup depth, neuroretinal
      rim area, rim volume, and smaller rim-optic disc area ratios than the other
      participants. No difference between African American and the other participants
      was found for cup shape and retinal nerve fiber layer thickness. After
      controlling for optic disc area, none of the differences between African American
      and the other participants found in the univariate analysis remained
      statistically significant (P>.10). CONCLUSIONS: This study demonstrated in a
      large cohort of subjects with ocular hypertension, that African Americans have
      significantly larger optic discs, optic cups, neuroretinal rims, and cup-disc
      ratios than other racial groups. Furthermore, this study found that differences
      in topographic optic disc parameters between African Americans with ocular
      hypertension and other racial groups are largely explained by the larger optic
      disc area in the African Americans. These results highlight the need to consider
      race and optic disc size when evaluating the appearance of the optic disc in
      glaucoma.

PMID- 14718291
TI  - Factors associated with long-term progression or stability in exfoliation
      glaucoma.
AB  - OBJECTIVE: To evaluate the effect of intraocular pressure (IOP) reduction on long
      term progression or stability in patients with exfoliation glaucoma. DESIGN:
      Multicenter (Greece, Spain, Russia, and Hungary), retrospective analysis.
      METHODS: Medical record analysis of 167 patients with at least 5 years of follow
      up, who were stable (n = 85) or whose condition had progressed (n = 82) after the
      beginning of the follow-up period. RESULTS: The mean +/- SD IOP was 18.1 +/- 2.6
      mm Hg in the stable group and 20.1 +/- 4.3 mm Hg in the progressed group
      (P<.001). The mean +/- SD follow-up time was 6.1 +/- 2.3 years for the stable
      group and 3.4 +/- 1.7 years for the progressed group. The mean SD for each
      patient's average IOP was 2.9 mm Hg for the stable group and 4.6 mm Hg for the
      progressed group (P<.001). Twenty-eight percent of patients who had a mean IOP of
      17 mm Hg or lower, 43% of those with an IOP of 18 to 19 mm Hg, and 70% of those
      with an IOP of 20 mm Hg or higher progressed. Progressed patients had
      statistically greater optic disc damage at baseline and more medication changes
      and trabeculectomies during follow-up than stable patients (P<.05). CONCLUSION:
      This study suggests that IOP reduction helps to prevent glaucoma progression in
      patients with exfoliation glaucoma, although it does not guarantee the prevention
      or worsening of the disease.

PMID- 14718292
TI  - Photodynamic therapy with verteporfin in subfoveal choroidal neovascularization
      secondary to central serous chorioretinopathy.
AB  - OBJECTIVE: To examine the efficacy and safety of photodynamic therapy with
      verteporfin in the treatment of subfoveal choroidal neovascularization secondary
      to central serous chorioretinopathy (CSC). DESIGN: Prospective interventional,
      noncomparative case series. METHODS: After the diagnosis of a subfoveal choroidal
      neovascularization secondary to CSC, 26 eyes of 24 patients were treated with
      photodynamic therapy with verteporfin. Patients were then followed up every 2 to
      3 months, with further treatments performed as deemed necessary through
      fluorescein angiography. The mean observation was 22.2 months (range, 6-36
      months; median, 24 months). RESULTS: There was marked visual improvement, with
      patients gaining a mean of 1.6 lines after 1 year and a mean of 2.2 lines after 2
      years. There was a statistically significant change in visual acuity from
      baseline to 12 and 24 months (mean difference, -0.16, P =.03; and mean
      difference, -0.22, P =.02; respectively; t test for both). There was no
      correlation between patients' age or greatest linear dimension of the lesions and
      the final outcome (P>.10 for all). No patient experienced any adverse effects.
      CONCLUSION: Photodynamic therapy with verteporfin resulted in a beneficial
      outcome in the treatment of subfoveal choroidal neovascularization secondary to
      CSC, without serious adverse effects in this case series.

PMID- 14718293
TI  - Determination of vitreous, aqueous, and plasma concentration of orally
      administered voriconazole in humans.
AB  - OBJECTIVE: To investigate the penetration of voriconazole, a new-generation
      triazole antifungal agent, into the vitreous and aqueous humor after oral
      administration. METHODS: A prospective, nonrandomized clinical study included 14
      patients scheduled for elective pars plana vitrectomy surgery between December 1,
      2002, and February 28, 2003, at the Cullen Eye Institute, Houston, Tex. Aqueous,
      vitreous, and plasma samples were obtained and analyzed from 14 patients after
      oral administration of two 400-mg doses of voriconazole taken 12 hours apart
      before surgery. Assays were performed by means of high-performance liquid
      chromatography. RESULTS: Mean +/- SD voriconazole concentrations in plasma (n =
      14), vitreous (n = 14), and aqueous (n = 11) were 2.13 +/- 0.93 microg/mL, 0.81
      +/- 0.31 microg/mL, and 1.13 +/- 0.57 microg/mL, respectively. Mean +/- SD
      sampling times after oral administration of the second voriconazole dose for
      plasma, vitreous, and aqueous were 2.4 +/- 0.6 hours, 3.0 +/- 0.5 hours, and 2.9
      +/- 0.5 hours, respectively. The percentages of plasma voriconazole concentration
      achieved in the vitreous and aqueous were 38.1% and 53.0%, respectively. Mean
      vitreous and aqueous minimum inhibitory concentrations for 90% of isolates
      (MIC(90)) were achieved against a wide spectrum of yeasts and molds, including
      Aspergillus species and Candida species, along with many other organisms.
      CONCLUSIONS: Orally administered voriconazole achieves therapeutic aqueous and
      vitreous levels in the noninflamed human eye, and the activity spectrum appears
      to appropriately encompass the most frequently encountered mycotic species
      involved in the various causes of fungal endophthalmitis. Because of its broad
      spectrum of coverage, low MIC(90) levels for the organisms of concern, good
      tolerability, and excellent bioavailability with oral administration, it may
      represent a major advance in the prophylaxis or management of exogenous or
      endogenous fungal endophthalmitis.

PMID- 14718294
TI  - Anterior ischemic optic neuropathy in eyes with optic disc drusen.
AB  - BACKGROUND: There have been anecdotal reports of anterior ischemic optic
      neuropathy (AION) occurring in eyes with optic disc drusen (ODD), but the
      clinical features of this condition have not been well characterized. OBJECTIVES:
      To better describe the clinical features of AION associated with ODD and to
      compare the clinical features of this condition with those of "garden variety"
      nonarteritic AION. METHODS: We reviewed the medical records of 20 patients who
      experienced an episode of AION in an eye with ODD. In 4 patients, both eyes were
      affected; thus, 24 eyes were studied. The diagnosis of ODD was made by
      ophthalmoscopic identification, orbital ultrasonography, or computed tomographic
      scanning. We recorded age, sex, vascular risk factors, symptoms, visual acuity,
      visual fields, and results of the follow-up examination in all patients. These
      findings were compared with data from previously reported series of patients with
      nonarteritic AION. RESULTS: Our 20 patients included 14 men and 6 women (age
      range, 18-69 years; mean, 49.4 years). Vascular risk factors were identified in
      10 patients (50%). Three patients reported episodes of transient visual loss
      before their fixed deficit. The visual acuity at the initial examination was
      20/60 or better in 15 (62%) of the 24 eyes; 8 had a visual acuity of 20/20. The
      predominant pattern of visual field loss was an altitudinal or arcuate defect in
      19 (79%) and a centrocecal scotoma in 5 (21%) of the 24 eyes. There was
      subjective worsening of vision before the initial neuro-ophthalmic examination in
      11 eyes (46%) and objective documentation of progression in 7 eyes (29%). The
      final visual acuity was 20/40 or better in 13 (62%) of 21 eyes and 20/200 or
      worse in 3 (14%) of 21 eyes. CONCLUSIONS: Our patients were strikingly similar to
      those with nonarteritic AION unassociated with drusen in regard to prevalence of
      vascular risk factors, pattern of visual field loss, and occurrence of a
      subsequent similar event in the fellow eye. In contrast, however, patients with
      ODD-AION were younger than those with nonarteritic AION, were more likely to
      report preceding episodes of transient visual obscuration, and enjoyed a more
      favorable visual outcome.

PMID- 14718295
TI  - Graded full-thickness anterior blepharotomy for upper eyelid retraction.
AB  - BACKGROUND: A chief morbidity of Graves eye disease is upper eyelid retraction
      that results in exposure keratopathy and cosmetic deformity. OBJECTIVE: To assess
      the efficacy of graded anterior blepharotomy to treat upper eyelid retraction.
      METHODS: Fifty eyelids of 32 patients with Graves eye disease-associated upper
      eyelid retraction, causing symptomatic ocular exposure, were treated with graded,
      transcutaneous, full-thickness, anterior blepharotomy. Preoperative and
      postoperative ocular exposure symptoms, upper eyelid position, lagophthalmos, and
      keratopathy were compared. RESULTS: At a mean +/- SD of 8.5 +/- 8.1 months'
      (range, 2-35 months) follow-up, more than 90% of preoperative symptoms resolved
      or improved. Upper eyelid position (P<.001), lagophthalmos (P<.001), and
      keratopathy (P<.01) were significantly improved. Mild contour abnormalities (all
      </=1 mm) occurred in 7 of 50 eyelids. Eyelid crease recession or asymmetry
      occurred in 4 of 22 patients with postoperative eyelid crease measurements.
      Complications of ptosis, wound dehiscence, and a full-thickness hole each
      occurred once. The mean +/- SD time taken to perform the procedure was 31.5 +/-
      8.9 minutes per eyelid. CONCLUSIONS: Graded anterior blepharotomy for upper
      eyelid retraction is a safe and highly effective surgery for upper eyelid
      retraction associated with symptomatic Graves eye disease. This technique
      achieves excellent functional and cosmetic outcomes.

PMID- 14718296
TI  - Late retinal detachment in patients born prematurely: outcome of primary pars
      plana vitrectomy.
AB  - OBJECTIVE: To describe the indications and results of pars plana vitrectomy for
      rhegmatogenous retinal detachment in patients born prematurely. PATIENTS AND
      METHODS: Between 1995 and 2001, primary vitrectomy for retinal detachment was
      performed in a consecutive series of 11 eyes of 10 patients. Gestational age
      ranged from 26 to 30 weeks, and birth weight ranged from 810 g to 1475 g.
      RESULTS: Myopia was found in 9 of 11 eyes. Two patients initially had a vitreous
      hemorrhage. One of these children was previously treated with cryotherapy during
      the acute phase of stage 3+ retinopathy of prematurity. Three eyes had a normal
      posterior pole and only mild peripheral retinal changes. Primary vitrectomy was
      performed in all 11 eyes. Patients received follow-up for 7.2 months to 6.6 years
      (mean, 2.7 years). Three eyes with severe cicatricial changes due to retinopathy
      of prematurity needed multiple procedures with silicone oil tamponade for
      reattachment. In 10 (90%) of 11 eyes, the retina was completely attached at the
      last follow-up visit. Visual acuity ranged from light perception to 20/25 in the
      affected eye. CONCLUSIONS: Patients born prematurely may develop late-onset
      retinal detachment due to vitreoretinal changes caused by retinopathy of
      prematurity. Primary vitrectomy is an effective treatment technique for retinal
      detachment in patients born prematurely.

PMID- 14718297
TI  - Treatment of experimental bacterial keratitis with topical trovafloxacin.
AB  - OBJECTIVE: To investigate the therapeutic role of trovafloxacin mesylate, a newer
      generation fluoroquinolone with an expanded spectrum of activity, in the
      treatment of experimental bacterial keratitis. METHODS: Susceptibility studies
      were performed on various strains of ocular isolates to determine the minimum
      inhibitory concentration (MIC) of trovafloxacin compared with ciprofloxacin and
      ofloxacin, using the E-test method. Pharmacokinetic studies were performed by a
      single topical administration of trovafloxacin to rabbit eyes with either an
      intact or denuded corneal epithelium. Aqueous humor, vitreous, and corneal
      concentrations of trovafloxacin were determined at different time points.
      Experimental bacterial keratitis studies were performed in rabbit eyes. Three
      identical studies were conducted using Staphylococcus aureus, Streptococcus
      pneumoniae, or Pseudomonas aeruginosa. Therapy groups included 0.5%
      trovafloxacin, 0.3% ciprofloxacin, 0.3% ofloxacin, and isotonic sodium chloride
      solution. After 12 hours of drops administration, corneas were excised,
      homogenized, and serially plated. The main outcome measure was quantitative
      bacteriologic analysis for residual colony-forming units. RESULTS: In vitro
      susceptibility study findings indicated that the MIC of trovafloxacin was
      significantly lower than the MIC of ciprofloxacin and ofloxacin for S. aureus, S.
      pneumoniae, and Haemophilus influenzae, lower than the MIC of ciprofloxacin and
      ofloxacin for Staphylococcus epidermidis, and intermediate between ciprofloxacin
      and ofloxacin for P. aeruginosa. Pharmacokinetic studies showed a significant
      concentration of trovafloxacin in the treated corneas, especially in eyes with a
      denuded epithelium. All serum samples had undetectable trovafloxacin
      concentrations. Experimental keratitis studies showed a statistically significant
      decrease of colony-forming units in trovafloxacin-treated eyes in the S. aureus
      model and a similar decrease in the S pneumoniae and P aeruginosa models.
      CONCLUSIONS: Topical 0.5% trovafloxacin proved to be an effective ocular
      medication for the therapy of gram-positive and gram-negative keratitis. Clinical
      Relevance Trovafloxacin may provide an excellent therapeutic alternative in
      bacterial keratitis.

PMID- 14718298
TI  - Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1)
      associated with retinitis punctata albescens: evidence of interfamilial genetic
      heterogeneity and fundus changes in heterozygotes.
AB  - OBJECTIVE: To evaluate the molecular genetic defects associated with retinitis
      punctata albescens (RPA) in 5 patients from 3 families with this disease.
      METHODS: We examined 3 probands and 2 clinically affected relatives with RPA.
      Clinical examinations included best-corrected visual acuity, visual field
      testing, electroretinography, dilated fundus examination, and fundus photography.
      Leukocyte DNA was analyzed for mutations in the exons of the genes encoding
      cellular retinaldehyde-binding protein 1 (RLBP1), 11-cis-retinol dehydrogenase
      (RDH5), interphotoreceptor retinoid-binding protein (RBP3), and photoreceptor all
      trans-retinol dehydrogenase (RDH8). Not all patients were evaluated for mutations
      in each gene. The exons were individually amplified and screened for mutations by
      single-stranded conformational polymorphism analysis or direct genomic
      sequencing. RESULTS: The 3 probands had similar clinical findings, including a
      history of poor night vision, the presence of punctate white deposits in the
      retina, and substantially reduced or absent rod responses on electroretinogram
      testing. One of the probands (patient 2:III:2) had 2 novel mutations in the RLBP1
      gene (Arg151Trp and Gly31[2-base pair deletion], [GGA-->G-]). Segregation
      analysis showed that the 2 mutations were allelic and that the patient was a
      compound heterozygote. Both parents of the proband manifested round white
      deposits in the retina. The other 2 probands had no detected pathogenic mutations
      in RLBP1 or in the other 3 genes evaluated. CONCLUSIONS: The identification of
      novel RLBP1 mutations in 1 of our 3 probands, all with RPA, is further evidence
      of genetic (nonallelic) heterogeneity in this disease. The presence of round
      white deposits in the retina may be observed in those heterozygous for RLBP1.
      Clinical Relevance Patients with a clinical presentation of RPA can have
      genetically different mutations. Drusen-like lesions may be observed in
      heterozygotes in families with this disease and a mutation in RLBP1.

PMID- 14718299
TI  - The relation of retinal vessel caliber to the incidence and progression of
      diabetic retinopathy: XIX: the Wisconsin Epidemiologic Study of Diabetic
      Retinopathy.
AB  - OBJECTIVE: To describe the relation of retinal arteriolar and venular caliber to
      the incidence and progression of diabetic retinopathy in people with type 1
      diabetes mellitus. DESIGN: Incidence findings in a population-based study of
      diabetic retinopathy in Wisconsin. Participants included 996 persons diagnosed as
      having diabetes mellitus before 30 years of age who took insulin and underwent
      the baseline examination, 891 in the 4-year follow-up, 765 in the 10-year follow
      up, and 634 in the 14-year follow-up. Retinal photographs of 7 standard fields
      were taken at all examinations. Computer-assisted grading was performed from a
      digitized image of field 1 to determine the average diameter of retinal
      arterioles and venules and their ratio. Main outcome measures included incidence
      and progression of retinopathy, incidence of proliferative retinopathy, and
      macular edema. RESULTS: While adjusting for other factors, larger arteriolar
      (relative risk [RR] for the fourth vs first quartile range, 2.04; 95% confidence
      interval [CI], 1.20-3.47; test of trend, P =.008) and venular diameters (RR,
      2.33; 95% CI, 1.37-3.95; test of trend, P =.005) were associated with greater 4
      year progression of retinopathy. Larger venular diameters (RR, 4.28; 95% CI, 1.50
      12.19; test of trend, P =.006) but not arteriolar diameters were associated with
      greater 4-year incidence of proliferative retinopathy. In multivariable analyses,
      arteriolar and venular calibers were not associated with the 4-year incidence of
      retinopathy. While adjusting for other factors, arteriolar and venular calibers
      were not associated with incidence of macular edema at 4 years. There were few
      associations of arteriolar or venular caliber with the 10- or 14-year incidence
      or the progression of retinopathy. CONCLUSIONS: Larger arteriolar and venular
      caliber, independent of retinopathy severity level, is related to the progression
      of retinopathy, and larger venular caliber is associated with the 4-year
      incidence of proliferative retinopathy. Caliber of retinal vessels is not
      associated with incident retinopathy. These data suggest a quantitative measure
      of retinal vascular caliber provides additional information regarding risk for
      progression of retinopathy.

PMID- 14718300
TI  - The impact of diabetic retinopathy on participation in daily living.
AB  - OBJECTIVE: To determine the restriction of participation in daily activities of
      people with diabetic retinopathy using the Impact of Vision Impairment
      questionnaire. METHODS: Individuals with diabetic retinopathy and a visual acuity
      (VA) worse than 20/40 or 6/12 in the better eye were eligible. Participants
      answered demographic questions and had VA information abstracted from medical
      records. If VA information was unavailable, it was assessed by an orthoptist.
      MAIN OUTCOME MEASURES: All participants completed the Impact of Vision Impairment
      questionnaire, which was either self-administered or interviewer administered.
      The physical and mental health components were assessed using the Medical
      Outcomes Study 12-Item Short Form (SF-12) questionnaire. RESULTS: Forty-five
      participants (mean age, 67.5 years) were recruited, with almost 70% (30/45)
      recording a VA worse than 20/60 or 6/18 in the better eye. The median duration of
      vision loss was 2.0 years. The highest restriction was reported for the Leisure
      and Work, Mobility, and Consumer and Social Interaction domains (mean, 3.0, 2.8,
      and 2.8, respectively), compared with the Emotional Reaction to Visual Loss and
      Household and Personal Care domains (mean, 2.3 and 2.1, respectively) (P<.005).
      The activities with the greatest restriction of participation were reading print,
      mobility, work, and leisure. A poorer VA in the better eye correlated
      independently with increased restriction of participation, as measured by the
      Impact of Vision Impairment questionnaire scores (partial correlations, 0.29
      0.41; P< or =.03). CONCLUSION: Low-vision rehabilitation services aiming to
      improve outdoor mobility, print reading, participation in leisure activities, and
      psychological health may be an effective strategy to help people with diabetic
      retinopathy increase their participation in daily activities.

PMID- 14718301
TI  - Absence of change in choroidal nevi across 5 years in an older population.
AB  - OBJECTIVE: To determine the proportion of choroidal nevi that were previously
      identified in a population cross section and that showed evidence of growth or
      progression during a 5-year period. METHODS: The Blue Mountains Eye Study was a
      cohort study of residents 49 years and older living in an area west of Sydney,
      Australia. Retinal photographs were used to identify choroidal nevi. Repeat
      photographs were obtained 5 years later and graded side-by-side to ascertain
      clinical growth or progression of all identified nevi. The greatest diameter and
      surface area of each nevus were measured. Nevus growth was defined as an increase
      in size of at least 33%. RESULTS: There were 160 choroidal nevi identified in the
      128 subjects with nevi who participated in both eye examinations. Only 1 nevus
      (0.6%) exhibited clinical growth during the 5 years. No nevi developed other
      indicators of progression, such as subretinal fluid or orange pigment
      accumulation. CONCLUSIONS: Findings from this study indicate that benign nevi in
      older persons rarely progress. Regular eye examinations may be unnecessary for
      clearly defined small nonsuspicious choroidal nevi. This information could
      relieve patient anxiety and reduce costs associated with regular monitoring of
      nevi.

PMID- 14718302
TI  - Informed consent and decision making by cataract patients.
AB  - OBJECTIVES: To investigate decision making by patients on the day before cataract
      surgery and to evaluate to what extent the informed consent process influences
      the patients' decision regarding consent. METHODS: On the day before surgery, 70
      patients (mean +/- SD age, 70.3 +/- 10.3 years) underwent a standardized informed
      consent procedure. They were also invited to answer 15 questions established in
      interdisciplinary cooperation among clinical psychologists, lawyers, and
      ophthalmologists. MAIN OUTCOME MEASURES: We assessed presurgical information and
      personal estimation of risks in cataract surgery; the patient-physician
      relationship regarding surgery-related decisions; and evaluations of the informed
      consent procedure and the patients' decision. RESULTS: Questionnaire answers
      indicated that 28 (40%) of the 70 participating patients arrived for surgery
      without any information; 16 (23%) believed that there were surgical procedures
      without risks; and 53 (76%) estimated that there were no risks for their cataract
      surgery. A physician-dominated decision for surgery was preferred by 31 patients
      (44%); 16 (26%) wanted to decide together with their ophthalmologist. Possible
      risks of a sight-threatening complication did not influence 54 patients' (77%)
      decisions, and 55 patients (78%) said the informed consent process did not
      influence their decision. The remaining 15 (22%) stated that the informed consent
      process positively confirmed their decision. CONCLUSIONS: Informed consent 1 day
      preoperatively does not seem to influence the decision for cataract surgery.
      Cognitive dissonance as part of a decision-making process makes changes in an
      already chosen option unlikely. The resulting limited decisive potential is very
      important for credibility in a trial and has to be considered in ophthalmologic
      surgery.

PMID- 14718303
TI  - Sir Frederick Treves and sympathetic ophthalmia.

PMID- 14718304
TI  - The case for glaucoma drainage implant surgery in patients with a poor prognosis
      for standard filtering procedure.

PMID- 14718306
TI  - Endonasal dacryocystorhinostomy: is it really less successful?

PMID- 14718305
TI  - The case against glaucoma drainage implant surgery in patients with a poor
      prognosis for standard filtering procedure.

PMID- 14718307
TI  - Isolated ectopia lentis: potential role of matrix metalloproteinases in fibrillin
      degradation.

PMID- 14718308
TI  - Orbital metastasis and intraocular invasion of malignant mixed tumor
      (carcinosarcoma) of the parotid gland in a child.

PMID- 14718309
TI  - Aggressive primary orbital melanoma in a young white man with no predisposing
      ocular features.

PMID- 14718310
TI  - Is coxsackievirus the cause of unilateral acute idiopathic maculopathy?

PMID- 14718311
TI  - Isolated vitreoretinal amyloidosis in the absence of transthyretin mutations.

PMID- 14718312
TI  - Optic nerve aplasia in an infant with congenital hypopituitarism and posterior
      pituitary ectopia.

PMID- 14718313
TI  - Visual improvement in an adult amblyopic eye following radiation-induced visual
      loss in the contralateral eye.

PMID- 14718314
TI  - Ischemic oculopathy as a complication of surgery for an atrial myxoma.

PMID- 14718315
TI  - Congenital vascular tortuosity in DiGeorge syndrome mimicking significant
      retinopathy of prematurity.

PMID- 14718316
TI  - Sunset, sunrise: old editor, new editor.

PMID- 14718317
TI  - Is signed consent for influenza or pneumococcal polysaccharide vaccination
      required?
AB  - Each year, thousands of preventable deaths and hospitalizations result from
      complications of influenza and pneumococcal disease, mostly in elderly persons,
      despite the availability of vaccines. Obtaining signed consent prior to
      administering the vaccines represents an obstacle to achieving the Healthy People
      2010 goals for vaccinating individuals against influenza and pneumococcal
      disease. Signed consent is neither legally mandated nor a guarantee that the
      patient (or proxy) has given informed consent. Nonetheless, many health care
      providers and institutions currently require signed consent before administering
      these vaccines. Rather, health care providers should use the Vaccine Information
      Sheets developed by the Centers for Disease Control and Prevention to inform
      patients about the risks and benefits associated with these vaccines. Requiring
      signed consent before administering these low-risk, high-benefit vaccines is
      inconsistent with the current practice of not requiring signed consent before
      prescribing other common treatments, eg, antibiotic treatment, whose risk levels
      are the same or higher.

PMID- 14718318
TI  - Relationship between deep venous thrombosis and the postthrombotic syndrome.
AB  - The postthrombotic syndrome (PTS) is a frequent complication of deep venous
      thrombosis (DVT). Clinically, PTS is characterized by chronic, persistent pain,
      swelling, and other signs in the affected limb. Rarely, ulcers may develop.
      Because of its prevalence, severity, and chronicity, PTS is burdensome and
      costly. Preventing DVT with the use of effective thromboprophylaxis in high-risk
      patients and settings and minimizing the risk of ipsilateral DVT recurrence are
      likely to reduce the risk of development of PTS. Daily use of compression
      stockings after DVT might reduce the incidence and severity of PTS, but
      consistent and convincing data about their effectiveness are not available.
      Future research should focus on standardizing diagnostic criteria for PTS,
      identifying patients at high risk for PTS, and rigorously evaluating the role of
      thrombolysis in preventing PTS and of compression stockings in preventing and
      treating PTS. In addition, novel therapies should be sought and evaluated.

PMID- 14718319
TI  - Effects of the amount of exercise on body weight, body composition, and measures
      of central obesity: STRRIDE--a randomized controlled study.
AB  - BACKGROUND: Obesity is a major health problem due, in part, to physical
      inactivity. The amount of activity needed to prevent weight gain is unknown.
      OBJECTIVE: To determine the effects of different amounts and intensities of
      exercise training. DESIGN: Randomized controlled trial (February 1999-July 2002).
      SETTING AND PARTICIPANTS: Sedentary, overweight men and women (aged 40-65 years)
      with mild to moderate dyslipidemia were recruited from Durham, NC, and
      surrounding communities. INTERVENTIONS: Eight-month exercise program with 3
      groups: (1) high amount/vigorous intensity (calorically equivalent to
      approximately 20 miles [32.0 km] of jogging per week at 65%-80% peak oxygen
      consumption); (2) low amount/vigorous intensity (equivalent to approximately 12
      miles [19.2 km] of jogging per week at 65%-80%), and (3) low amount/moderate
      intensity (equivalent to approximately 12 miles [19.2 km] of walking per week at
      40%-55%). Subjects were counseled not to change their diet and were encouraged to
      maintain body weight. MAIN OUTCOME MEASURES: Body weight, body composition (via
      skinfolds), and waist circumference. RESULTS: Of 302 subjects screened, 182 met
      criteria and were randomized and 120 completed the study. There was a significant
      (P<.05) dose-response relationship between amount of exercise and amount of
      weight loss and fat mass loss. The high-amount/vigorous-intensity group lost
      significantly more body mass (in mean [SD] kilograms) and fat mass (in mean [SD]
      kilograms) (-2.9 [2.8] and -4.8 [3.0], respectively) than the low-amount/moderate
      intensity group (-0.9 [1.8] and -2.0 [2.6], respectively), the low
      amount/vigorous-intensity group (-0.6 [2.0] and -2.5 [3.4], respectively), and
      the controls (+1.0 [2.1] and +0.4 [3.0], respectively). Both low-amount groups
      had significantly greater improvements than controls but were not different from
      each other. Compared with controls, all exercise groups significantly decreased
      abdominal, minimal waist, and hip circumference measurements. There were no
      significant changes in dietary intake for any group. CONCLUSIONS: In nondieting,
      overweight subjects, the controls gained weight, both low-amount exercise groups
      lost weight and fat, and the high-amount group lost more of each in a dose
      response manner. These findings strongly suggest that, absent changes in diet, a
      higher amount of activity is necessary for weight maintenance and that the
      positive caloric imbalance observed in the overweight controls is small and can
      be reversed by a modest amount of exercise. Most individuals can accomplish this
      by walking 30 minutes every day.

PMID- 14718320
TI  - Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular
      disease: randomized and observational comparisons of secondary prevention trials
      and their meta-analyses.
AB  - BACKGROUND: In randomized trials of secondary prevention, pravastatin sodium and
      aspirin reduce risks of cardiovascular disease. Pravastatin has a predominantly
      delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect,
      raising the possibility of additive clinical benefits. METHODS: In 5 randomized
      trials of secondary prevention with pravastatin (40 mg/d), comprising 73 900
      patient-years of observation, aspirin use was also prescribed in varying
      frequencies, and data were available on a large number of confounding variables.
      We tested whether pravastatin and aspirin have additive benefits in the 2 large
      trials (Long-term Intervention With Pravastatin in Ischaemic Disease trial and
      the Cholesterol and Recurrent Events trial) that were designed to test clinical
      benefits. We also performed meta-analyses of these 2 trials and 3 smaller
      angiographic trials that collected clinical end points. In all analyses,
      multivariate models were used to adjust for a large number of cardiovascular
      disease risk factors. RESULTS: Individual trials and all meta-analyses
      demonstrated similar additive benefits of pravastatin and aspirin on
      cardiovascular disease. In meta-analysis, the relative risk reductions for fatal
      or nonfatal myocardial infarction were 31% for pravastatin plus aspirin vs
      aspirin alone and 26% for pravastatin plus aspirin vs pravastatin alone. For
      ischemic stroke, the corresponding relative risk reductions were 29% and 31%. For
      the composite end point of coronary heart disease death, nonfatal myocardial
      infarction, coronary artery bypass graft, percutaneous transluminal coronary
      angioplasty, or ischemic stroke, the relative risk reductions were 24% and 13%.
      All relative risk reductions were statistically significant. CONCLUSION: More
      widespread and appropriate combined use of statins and aspirin in secondary
      prevention of cardiovascular disease will avoid large numbers of premature
      deaths.

PMID- 14718321
TI  - Cost-effectiveness of postexposure prophylaxis after sexual or injection-drug
      exposure to human immunodeficiency virus.
AB  - BACKGROUND: The cost-effectiveness of interventions that provide human
      immunodeficiency virus (HIV) postexposure prophylaxis (PEP) to individuals after
      sexual or injection-drug use exposures depends on the distribution of exposure
      routes, prevalence of infection among source partners, adherence to PEP regimens,
      medical care costs, and prevailing epidemiologic contexts, among other factors.
      OBJECTIVE: To determine the cost-effectiveness of a comprehensive program to
      prevent HIV infection after sexual or injection-drug use exposure for 401 persons
      seeking PEP in an urban community. METHODS: We conducted a retrospective cost
      analysis to evaluate the cost of the PEP intervention, then combined this
      information with model-based effectiveness estimates to determine the PEP
      program's "cost-utility ratio," which is the ratio of net program costs to the
      total number of quality-adjusted life-years (QALYs) saved by the program.
      RESULTS: The average cost of the PEP regimen was $1222, and the total cost of the
      program was $450 970. The PEP program prevented an estimated 1.26 HIV infections,
      saved 11.74 QALYs, and averted $281 323 in future HIV-related medical care costs.
      The overall cost-utility ratio was $14 449 per QALY saved. When analysis was
      restricted to men reporting receptive anal intercourse, the savings in averted
      HIV-related medical care costs exceeded the cost of the program. The results were
      generally robust to changes in key parameter values but were sensitive to
      assumptions about the HIV transmission probability for receptive anal
      intercourse. CONCLUSIONS: For this study population, HIV PEP was cost-effective
      by conventional standards and cost-saving for persons seeking PEP after male-male
      receptive anal intercourse.

PMID- 14718322
TI  - National trends in antiarrhythmic and antithrombotic medication use in atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia associated
      with significant medical complications. We examined trends in the medical therapy
      of atrial fibrillation in the United States from 1991 through 2000. METHODS: Data
      from 1355 visits among patients with atrial fibrillation were obtained from the
      National Ambulatory Medical Care Survey, a nationally representative assessment
      of office-based practice. We assessed trends in medication use for ventricular
      rate control (digoxin, beta-blockers, and calcium channel blockers), sinus rhythm
      maintenance (class IA, IC, and III antiarrhythmics), and thromboembolism
      prevention (oral anticoagulants and aspirin). RESULTS: Overall rate control
      medication use decreased from 72% of visits in 1991-1992 to 56% in 1999-2000 (P
      =.01 for trend) due to declining digoxin use (64% to 37%, P<.001 for trend). beta
      Blocker and calcium channel blocker use remained unchanged. Although there was no
      change in overall sinus rhythm medication use over time, amiodarone hydrochloride
      use increased from 0.2% to 6.4% (P<.001 for trend), while quinidine use decreased
      from 5.0% to 0.0% (P =.01 for trend). Oral anticoagulant use increased (28% to
      41%, P =.01 for trend), with the greatest increase in patients aged 80 years and
      older (14% to 48%, P<.001 for trend). Despite this, only 46.5% of patients at
      high risk for stroke were taking anticoagulants in 1999-2000. CONCLUSIONS:
      Digoxin use in atrial fibrillation decreased over time, without concomitant
      increases in beta-blocker or calcium channel blocker use. Amiodarone replaced
      quinidine as the dominant sinus rhythm medication. Although oral anticoagulant
      use increased over time, particularly in the oldest patients, fewer than half of
      the patients at high risk for stroke were anticoagulated.

PMID- 14718323
TI  - Effect of patient sex on intensive care unit survival.
AB  - BACKGROUND: Human observations have shown different mortality rates between men
      and women with various pathological conditions, but this issue has not been
      widely studied in a heterogeneous population of critically ill patients. METHODS:
      Retrospective analysis of all patients admitted to a mixed medical-surgical, 31
      bed intensive care unit (ICU) during 2 different years (1983 and 1995) to
      evaluate possible differences in mortality between male and female patients and
      between medical and surgical admissions and variations in these differences over
      time. RESULTS: From a total of 4420 admissions (1587 women, 2833 men), women
      showed a higher mortality, with an odds ratio (OR) of 1.18 (95% confidence
      interval [CI], 1.02-1.38). This pattern was the same for the 2 periods, and all
      patient data were therefore analyzed together. After age stratification, the
      differences were significant for female patients older than 50 years (OR, 1.33;
      95% CI, 1.12-1.58) but not in the younger age group. The subgroup of medical
      admissions had a higher mortality (24.4% vs 7.4%, P<.001) and a higher female
      proportion (37.9% vs 34.2%, P =.01) than surgical admissions. In multivariate
      analysis, female sex remained an important predictor of mortality (OR, 1.54; 95%
      CI, 1.25-1.89). Women had a higher mortality than men in the subgroup of
      cardiovascular diseases. The highest mortality in female patients was present in
      the first days after admission and decreased over time, showing a covariance of
      time and sex. CONCLUSIONS: In a mixed medical-surgical ICU, older women have a
      higher mortality rate than men. This difference is not apparent for patients
      staying longer in the ICU.

PMID- 14718324
TI  - Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin
      induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a common, often
      catastrophic, syndrome that produces the most hypercoagulable of states. Emerging
      therapeutic strategies use alternative anticoagulants; warfarin's place is being
      reexamined. Early in the course of warfarin therapy, there may be net
      procoagulant effects because of the inhibition of protein C. With HIT, it has
      been suggested that unopposed warfarin can precipitate venous limb gangrene.
      There are also reports of warfarin-induced skin necrosis. We seek to confirm and
      increase awareness of the risks of warfarin with HIT. METHODS: We describe 6
      patients with HIT seen at 3 medical centers in whom frank or impending venous
      limb gangrene, central skin necrosis, or both were temporally related to warfarin
      initiation. RESULTS: At warfarin initiation, 5 patients had recognized HIT and 1
      had it recognized later. Complications emerged after 2 to 7 days, and consisted
      of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1
      patient had both. This emerged with unopposed warfarin in 4 patients and as a
      direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic
      international normalized ratios. One patient required leg and breast amputations,
      and another one died. CONCLUSIONS: Because of the early effects on protein C,
      warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme
      hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and
      caution is needed during transition from a direct thrombin inhibitor. Warfarin
      should be initiated at modest doses in patients with HIT after platelet recovery.
      Implications extend to warfarin initiation with other thrombotic diatheses.

PMID- 14718325
TI  - Infective endocarditis in patients with end-stage renal disease: clinical
      presentation and outcome.
AB  - BACKGROUND: Infective endocarditis is a common complication of vascular access in
      patients undergoing long-term hemodialysis. However, available data are either
      dated or gathered from small samples. The goal of this study was to investigate
      the clinical characteristics and outcome of infective endocarditis occurring in
      patients with end-stage renal disease. METHODS: Patients were identified by
      computerized discharge diagnosis and manual chart review at 3 major hospitals in
      Honolulu, Hawaii. The search covered an 11-year period, through December 2001.
      Modified Duke criteria were retrospectively applied. Patients fulfilling criteria
      for definite endocarditis were included in this study. RESULTS: Forty patients
      were identified. Average age was 59.4 years, and average duration of hemodialysis
      before endocarditis was 3.3 years; arteriovenous fistulas were the most commonly
      used access sites. Predominant organism was Staphylococcus aureus in 20 (50%) of
      the 40 cases. The mitral valve was affected in 29 cases (73%); aortic and mitral
      valve endocarditis was seen in 8 cases (20%). Overall in-hospital mortality was
      52% (21/40). Patients with an unfavorable outcome more often had fever on
      admission, fewer negative blood cultures, and bivalvular infective endocarditis,
      and more often underwent valve replacement surgery. The perioperative mortality
      in patients undergoing valve replacement was 73% (11/15). CONCLUSIONS: Mortality
      of infective endocarditis in patients with end-stage renal disease remains high
      and has been essentially unchanged during the past decade. If patients require
      valve replacement surgery, mortality is even higher. A randomized, controlled
      trial is needed to clarify whether the increased mortality is due solely to more
      severe disease in patients requiring valve replacement surgery.

PMID- 14718326
TI  - High impact of antiphospholipid syndrome on irreversible organ damage and
      survival of patients with systemic lupus erythematosus.
AB  - BACKGROUND: Thrombosis is a frequent cause of morbidity and death in patients
      with systemic lupus erythematosus (SLE). Whether antiphospholipid syndrome (APS)
      is the cause of increased irreversible organ damage and mortality in lupus
      patients is not well established. METHODS: Prospective inception cohort of 202
      patients with SLE (American College of Rheumatology criteria). Antiphospholipid
      syndrome was defined according to the Sapporo criteria. Irreversible damage was
      measured using the Systemic Lupus International Collaborating Clinics-American
      College of Rheumatology damage index (SDI) at 6 months and 1, 3, 5, 10, 15, 20,
      and 25 years after the diagnosis of SLE. All deaths were documented. RESULTS: A
      total of 88% of patients were women. Twenty-eight patients met criteria for
      definite APS. Mean (SD) follow-up was 9.7 (6.0) years. Nine patients could not be
      contacted for follow-up. All patients with APS experienced thrombosis, most of
      them in the arterial bed. Damage was more severe in patients with APS than in
      those without APS (median SDI score, 2 vs 0 at 5 years; P<.001; 4 vs 1 at 15
      years; P<.001). Cumulative survival at 15 years was lower in patients with APS
      than in those without APS (65% vs 90%, P =.03). Older age at diagnosis, lupus
      nephritis, and APS were independent predictors of mortality. CONCLUSIONS:
      Antiphospholipid syndrome with thrombotic manifestations is a major predictor of
      irreversible organ damage and death in patients with SLE.

PMID- 14718327
TI  - The comprehensive care team: a controlled trial of outpatient palliative medicine
      consultation.
AB  - BACKGROUND: Little is known about the use of palliative care for outpatients who
      continue to pursue treatment of their underlying disease or whether outpatient
      palliative medicine consultation teams improve clinical outcomes. METHODS: We
      conducted a year-long controlled trial involving 50 intervention patients and 40
      control patients in a general medicine outpatient clinic. Primary care physicians
      referred patients with advanced congestive heart failure, chronic obstructive
      pulmonary disease, or cancer who had a prognosis ranging from 1 to 5 years. In
      the intervention group, the primary care physicians received multiple palliative
      care team consultations, and patients received advance care planning,
      psychosocial support, and family caregiver training. Clinical and health care
      utilization outcomes were assessed at 6 and 12 months. RESULTS: Groups were
      similar at baseline. Similar numbers of patients died during the study year (P
      =.63). After the intervention, intervention group patients had less dyspnea (P
      =.01) and anxiety (P =.05) and improved sleep quality (P =.05) and spiritual well
      being (P =.007), but no change in pain (P =.41), depression (P =.28), quality of
      life (P =.43), or satisfaction with care (P =.26). Few patients received
      recommended analgesic or antidepressant medications. Intervention patients had
      decreased primary care (P =.03) and urgent care visits (P =.04) without an
      increase in emergency department visits, specialty clinic visits,
      hospitalizations, or number of days in the hospital. There were no differences in
      charges (P =.80). CONCLUSIONS: Consultation by a palliative medicine team led to
      improved patient outcomes in dyspnea, anxiety, and spiritual well-being, but
      failed to improve pain or depression. Palliative care for seriously ill
      outpatients can be effective, but barriers to implementation must be explored.

PMID- 14718328
TI  - Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism.
AB  - BACKGROUND: In patients with a first symptomatic pulmonary embolism (PE), the
      risk of recurrence is unknown. We therefore investigated the risk of recurrence
      among patients with spontaneous symptomatic PE and among those with deep vein
      thrombosis (DVT) without symptoms of PE. METHODS: After discontinuation of
      secondary thromboprophylaxis for a first venous thromboembolism (VTE), we
      prospectively observed 436 patients for an average of 30 months. Patients with
      secondary VTE, natural inhibitor deficiencies, lupus anticoagulant, cancer, long
      term antithrombotic therapy, vena cava filters, or pregnancy were excluded. The
      study outcome was objectively documented recurrent symptomatic VTE. RESULTS:
      Recurrent VTE was seen among 28 (17.3%) of 162 patients with symptomatic PE and
      among 26 (9.5%) of 274 patients with DVT without symptoms of PE. Compared with
      patients with DVT, the relative risk of recurrent VTE among patients with
      symptomatic PE was 2.2 (95% confidence interval, 1.3-3.7; P =.005). The relative
      risk was not affected by age, sex, presence of factor V Leiden or prothrombin
      G20210A, hyperhomocysteinemia, or high factor VIII levels. Compared with patients
      with DVT without symptoms of PE, patients with symptomatic PE had an adjusted
      relative risk of PE at recurrence of 4.0 (95% confidence interval, 1.3-12.3; P
      =.03). CONCLUSION: Patients with a first symptomatic PE not only have a higher
      risk of recurrent VTE than those with DVT without symptoms of PE, but are also at
      high risk of symptomatic PE at recurrence.

PMID- 14718329
TI  - Prevalence and risk factors of morning headaches in the general population.
AB  - OBJECTIVE: To determine the prevalence of chronic morning headaches (CMH) in the
      general population and their relationship to sociodemographic characteristics,
      psychoactive substance use, and organic, sleep, and mental disorders. METHODS: A
      telephone questionnaire was submitted to 18 980 individuals 15 years or older and
      representative of the general populations of the United Kingdom, Germany, Italy,
      Portugal, and Spain. It included a series of questions about morning headaches,
      organic disorders, use of psychoactive substances, and sleep and mental disorders
      in accordance with the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV). RESULTS: Overall, the prevalence of CMH was 7.6% (n =
      1442); CMH were reported to occur "daily" by 1.3% of the sample, "often" by 4.4%,
      and "sometimes" by 1.9%. Rates were higher in women than in men (8.4% vs 6.7%)
      and in subjects aged between 45 and 64 years (about 9%). The median duration for
      CMH was 42 months. Various conditions and disorders were found positively
      associated with CMH. The most significant associated factors were comorbid
      anxiety and depressive disorders (28.5% vs 5.5%), major depressive disorder alone
      (21.3% vs 5.5%), dyssomnia not otherwise specified (17.1% vs 6.9%), insomnia
      disorder (14.4% vs 6.9%), and circadian rhythm disorder (20.0% vs 7.5%). Sleep
      related breathing disorder (15.2% vs 7.5%), hypertension (11.0% vs 7.2%),
      musculoskeletal diseases (14.1% vs 7.1%), use of anxiolytic medication (20.1% vs
      7.3%), and heavy alcohol consumption (12.6% vs 7.7%) were also significantly
      associated with CMH. CONCLUSIONS: Morning headache affects 1 individual in 13 in
      the general population. Chronic morning headaches are a good indicator of major
      depressive disorders and insomnia disorders. Contrary to what was previously
      suggested, however, they are not specific to sleep-related breathing disorder.

PMID- 14718330
TI  - Aortic stenosis and gastrointestinal bleeding.

PMID- 14718331
TI  - Prospective investigation of adverse effects of acupuncture in 97 733 patients.

PMID- 14718332
TI  - Iatrogenic eosinophilia.

PMID- 14718333
TI  - Anticoagulant-related bleeding risk in older persons: unfounded fears?

PMID- 14718334
TI  - Risks and benefits of statins in lupus erythematosus.

PMID- 14718335
TI  - Clarification on heart sound.

PMID- 14718336
TI  - Aortic valvular stenosis vs aortic valvular sclerosis.

PMID- 14718337
TI  - Evidence-based use of rheumatologic laboratory tests.

PMID- 14718338
TI  - Obesity and Alzheimer disease: roles of diet and genetics.

PMID- 14718340
TI  - The orientation-averaged aspiration efficiency of IOM-like personal aerosol
      samplers mounted on bluff bodies.
AB  - This paper describes two sets of experiments that were intended to characterize
      the orientation-averaged aspiration efficiencies of IOM samplers mounted on
      rotating bluff bodies. IOM samplers were mounted on simplified, three-dimensional
      rectangular bluff bodies that were rotated horizontally at a constant rate.
      Orientation-averaged aspiration efficiencies (A360) were measured as a function
      of Stokes' number (St), velocity ratio (R) and dimension ratio (r). Aspiration
      efficiency (A) is the efficiency with which particles are transported from the
      ambient air into the body of a sampler, and A360 is A averaged over all
      orientations to the wind. St is a dimensionless variable that represents particle
      inertia, R is the ratio of the air velocity in the freestream and that at the
      plane of the sampler's entry orifice, and r is the ratio of the sampler's orifice
      diameter and the bluff body's width. The first set of experiments were
      instrumental in establishing a hierarchy of effects on orientation-averaged A. It
      was clear that compared to r, St had a much larger influence on A. It was also
      clear, however, that the effects of St were overpowered by the effects of R in
      many cases. As concluded in previous studies, R and St were considered the most
      important factors in determining A, even for A360. The second set of experiments
      investigated A360 of IOM samplers for a much wider range of r than examined in
      previous research. Two important observations were made from the experimental
      results. One was that the A360 of IOM samplers, as a function of St, did not
      change for an r-range of 0.066-0.4. This meant that an IOM sampler mounted on a
      near life-size mannequin would measure the same aerosol concentration as one not
      mounted on anything. The second observation was that the aspiration efficiency
      curve of the IOM sampler was close to the inhalability curve. This gave further
      evidence that the bluff body did not play a major role in influencing A360, as
      the IOM samplers, in these experiments, were either mounted on miniature bluff
      bodies or on nothing at all. These observations all suggest that it is quite
      possible to design and test personal samplers with desired sampling
      characteristics using protocols that do not require full-size mannequins, which
      greatly simplifies the development of new samplers.

PMID- 14718341
TI  - Method-induced misclassification for a respirable dust sampled using
      ISO/ACGIH/CEN criteria.
AB  - The single cut measurement of exposure to respirable dust is the accepted method
      of exposure classification in occupational hygiene. We previously showed that
      actual pulmonary tissue dose may be substantially different from the dose
      expected, or the indicated dose, based on measurements using current single cut
      methodologies. We now examine exposure misclassification of workers based on any
      single cut respirable dust measurement using the internationally accepted
      ISO/ACGIH/CEN single cut respirable dust measurement criteria. Hypothetical
      aerosols with 12 generalized size distributions typical of the method of aerosol
      generation (condensation, aged condensation, mechanical low energy, mechanical
      high energy and mixtures thereof) were assumed. Using previously reported models
      for sampler penetration and pulmonary deposition, Monte Carlo simulations of
      actual mass dose to pulmonary tissues in comparison to the dose estimate from an
      ideal respirable aerosol sampler were carried out. Measurement-based indicated
      doses were used to classify exposures into five exposure categories and these
      classifications were compared with the 'true' classifications from the dose-based
      exposure estimates. Misclassification rates were generally severe and were
      greatest for aerosols with mass median aerodynamic diameter (MMAD) <1 microm
      (approximately 100%) and MMAD 5-15 microm (65-95%). Misclassification rates were
      moderate (<20%) only for extremely coarse aerosols of MMAD>15 microm.
      Misclassification rates for oral and nasal breathing at 750 and 1500 ml tidal
      volume and 15 breaths/min were similar for each aerosol examined.

PMID- 14718342
TI  - Contact allergy in construction workers: results of a multifactorial analysis.
AB  - OBJECTIVES: To quantify the risk of contact allergy (CA) to important ubiquitous
      allergens associated with certain occupations, in particular the construction
      industry, and to identify possible time trends, controlling for potential
      confounding variables. METHODS: Bivariate as well as Poisson regression analysis
      of standardized anamnestic and patch test data comprising 82,561 patients
      assessed in the 33 German and Austrian contact dermatitis units of the
      Information Network of Departments of Dermatology (IVDK) between 1992 and 2000.
      RESULTS: CA to five of the 18 (groups of) allergens considered here were observed
      significantly more often in construction workers: dichromate, epoxy resin
      (BADGE), cobalt, thiurams and N-isopropyl-p-phenylenediamine (IPPD).
      Multifactorial analysis confirmed an increased risk of CA to these allergens in
      construction workers, compared with other occupations. A very strong association
      between cobalt and chromate allergy was found in construction workers (OR 39.1,
      95% CI 21.1-79.6). CONCLUSIONS: Dichromate is still an prominent allergen in
      construction workers; as yet, there is only weak evidence of a decrease in
      Germany. Therefore, the addition of ferrous sulphate to cement, which has been a
      successful intervention in other countries, should be promoted further. Although
      CA to other important occupational allergens like thiurams, IPPD and epoxy resin
      or cobalt (very often associated with dichromate CA) is less frequent, prevention
      should address these allergens, too. The use of protective gloves with minimal
      intrinsic CA risk, e.g. due to thiurams in (synthetic) rubber or chromate in
      leather gloves, should be promoted.

PMID- 14718343
TI  - Photometry in the workplace: the rationale for a new method.
AB  - OBJECTIVES: The assessment of lighting conditions in workplaces has traditionally
      focused on the measurement of illuminance. The rationale for a new method for the
      detailed evaluation of natural and artificial light in 'near work' situations,
      involving the assessment of luminance, is described. METHODS: The procedure
      comprises four successive phases: (1) identify object/images observed during work
      tasks; (2) outline the area of the operator's visual field where gaze is
      predominantly directed; (3) measure luminances in the visual field, pin-pointing
      all sources of primary and secondary luminance, and constructing iso-luminance
      maps; and (4) compare luminance ratios. RESULTS: The procedure was illustrated
      using the common example of near work in an office environment. Illuminance was
      found to be inadequate to evaluate the effects of natural and artificial
      environmental light in the workplace. This is due to the fact that the luxmeter
      is designed to integrate the light detected over a large angle, whereas in near
      work the operator's retina is mainly stimulated by light originating from
      objects/images placed in the occupational visual field. CONCLUSIONS: A detailed
      measurement of luminance within the occupational visual field is consistent with
      ocular anatomy and physiology, and can be used as part of a risk assessment for
      visual disturbances and to rationalize lighting at workstations.

PMID- 14718344
TI  - An evaluation of the standardized chipping hammer test specified in ISO 8662-2.
AB  - OBJECTIVES: Prolonged exposure to severe chipping hammer vibration may cause hand
      arm vibration syndrome. A reliable test method is required to select appropriate
      tools and assist in the development of better chipping hammers. In the present
      study, the ISO standardized test method (ISO 8662-2, 1992) was examined through
      an investigation of the vibration characteristics of chipping hammers operating
      on the energy absorber specified in the standard. METHODS: The energy absorber
      and test setup were designed and constructed based on those specified in the
      standard. The experiment employed six subjects and used two pneumatic chipping
      hammers and three different feed forces (50, 100 and 200 N). The subject posture
      was the same as that specified in the standard. RESULTS: The vibration emission
      at the tool dominant frequency (or air blow rate) generally declined with an
      increase in feed force, thus decreasing the frequency-weighted accelerations. The
      increase in feed force, however, resulted in an increase in the unweighted
      vibration emission at high frequencies. The chipping hammer vibration emission
      operating on the energy absorber at the high feed force (200 N) was inconsistent.
      CONCLUSIONS: The measurement method has a good repeatability except at a high
      feed force. The feed force has a significant effect on the vibration emission.
      The single feed force specified in the standard may not be sufficient to test the
      tool behaviors. Multiple levels of feed force should be used for the chipping
      hammer test. Doing so may provide a more appropriate basis for tool screening.

PMID- 14718345
TI  - Worker exposure to polychlorinated biphenyls in elastic polysulphide sealant
      renovation.
AB  - Worker exposure to polychlorinated biphenyls (PCBs) in renovation of
      prefabricated houses was assessed by biological monitoring of 24 PCB congeners
      including the 10 most abundant PCBs in elastic polysulphide sealants. Serum
      samples from 22 exposed and 21 non-exposed men were analysed using gas
      chromatography-mass spectrometry with negative chemical ionization. Total PCB
      concentration of 24 PCB congeners in workers' serum varied between 0.6 and 17.8
      microg/l (mean 3.9 microg/l, median 1.9 microg/l). The Finnish upper reference
      limit for occupationally non-exposed persons (3 microg/l) was exceeded in the
      serum samples of 10 workers. Concentrations for non-exposed persons were 0.3-3.0
      microg/l (mean 1.7 microg/l, median 1.5 microg/l). The concentration for the sum
      of the 10 most abundant PCB congeners in elastic polysulphide sealants in serum
      samples taken in autumn after the renovation season was 2-10 times higher than in
      samples from the same workers (n=5) taken in the previous spring. The
      concentrations of PCB congeners PCB 28, 52, 77, 101, 138, 153 and 180 in hygienic
      samples taken from the breathing zone of the workers were low, ranging from not
      detected to 3.1 microg/m3. The concentrations of PCB 28 and 52 in sera were
      positively correlated with the concentrations in air samples taken from the
      breathing zone of six workers (r=0.70 and 0.80).

PMID- 14718346
TI  - Exposure to inhalable dust, wheat flour and alpha-amylase allergens in industrial
      and traditional bakeries.
AB  - This study was designed to characterize exposure to inhalable dust, wheat flour
      and alpha-amylase allergens in industrial and traditional bakeries. The study
      included 70 bakeries from the northern part of Belgium. Based on the degree of
      automation and a clear division of individual job tasks, four bakeries were
      identified as industrial and the remaining 66 were identified as traditional
      ones. Personal, as well as stationary, samples of inhalable dust were collected
      during full shift periods, usually 5-7 h. The portable pumps aspirated 2 l/min
      through Teflon personal dust samplers (Millipore, pore size 1.0 microm) mounted
      in PAS-6 sampling heads. In the collected samples the inhalable dust, wheat flour
      and alpha-amylase allergens were determined. Wheat flour allergens were measured
      using enzyme-linked immunosorbent assay inhibition and an antiwheat IgG4 serum
      pool. The alpha-amylase allergens were measured using a sandwich enzyme
      immunoassay with affinity-purified polyclonal rabbit IgG antibodies. In total,
      440 samples (300 personal and 140 stationary) were processed. The highest
      inhalable dust exposure was observed in traditional bakeries among bread
      [geometric mean (GM) 2.10 mg/m3] and bread and pastry workers (GM 1.80 mg/m3). In
      industrial bakeries the highest dust exposure was measured in bread-producing
      workers (GM 1.06 mg/m3). Similar relations were observed for wheat flour and
      alpha-amylase allergens. Bread baking workers in traditional bakeries had the
      highest exposure to both allergens (wheat flour GM 22.33 microg/m(3), alpha
      amylase GM 0.61 ng/m3). The exposure to wheat flour and alpha-amylase allergens
      in industrial bakeries was higher in bread baking workers (wheat flour GM 6.15
      microg/m3, alpha-amylase GM 0.47 ng/m3) than in bread packing workers (wheat
      flour GM 2.79 microg/m3, alpha-amylase GM 0.15 ng/m3). The data presented suggest
      that, on average, exposure in the Belgium bakeries studied-industrial as well as
      traditional-is lower than or similar to bakeries in The Netherlands, Canada,
      Sweden, the United Kingdom and Finland. Furthermore, the exposure levels in
      traditional bakeries seem to be higher than in industrial bakeries.

PMID- 14718347
TI  - Determination of keratin protein in a tape-stripped skin sample from jet fuel
      exposed skin.
AB  - Chemical contaminants or their metabolites may bind to and react with keratin
      proteins in the stratum corneum of the skin. Here, we present a tape-stripping
      method for the removal and quantification of keratin from the stratum corneum for
      normalization of extracted concentrations of naphthalene (as a marker for jet
      fuel exposure) from 12 human volunteers before and after exposure to jet fuel (JP
      8). Due to the potential for removal of variable amounts of squamous tissue from
      each tape-strip sample, keratin was extracted and quantified using a modified
      Bradford method. Confirmation of the extraction of keratin was verified by
      western blotting using a monoclonal mouse anti-human cytokeratin antibody.
      Naphthalene was quantified in the sequential tape strips collected from the skin
      between 10 and 25 min after a single dose of JP-8 was initially applied. The
      penetration of jet fuel into the stratum corneum was demonstrated by the fact
      that the average mass of naphthalene recovered by a tape strip decreased with
      increased exposure time and subsequent tape strips and that the evaporation of
      naphthalene was observed to be negligible. There were no significant differences
      in the amount of keratin or naphthalene removed by tape strips between males and
      females, between age groups, races or degrees of skin pigmentation. We conclude
      that (i) the amount of keratin removed with tape strips was not affected by up to
      a 25 min exposure to JP-8 and (ii) there was a substantial decrease in the amount
      of keratin removed with consecutive tape strips from the same site, thus,
      adjusting the amount of naphthalene by the amount of keratin measured in a tape
      strip sample should improve the interpretation of the amount of this analyte
      using this sampling approach. Although we found that normalization of the
      naphthalene to the amount of keratin in the tape-strip samples did not affect the
      ability of this method to quantify the dermal exposure to JP-8 under these
      laboratory conditions, the actual concentration of naphthalene (as a marker for
      JP-8 exposure) per unit of keratin in a tape-strip sample can be determined using
      this method and may prove to be required when measuring occupational exposures
      under field conditions.

PMID- 14718349
TI  - Retraction.

PMID- 14718348
TI  - Determination of short-term exposure with a direct reading photoionization
      detector.
AB  - The use of a direct reading photoionization detector (PID) to determine short
      term solvent exposures is described in the present paper. To assess the relevance
      of such a total exposure evaluation it was necessary to compare it with the real
      concentration of pollutants. This comparison was made by measuring in parallel
      with the PID determination the concentration of each pollutant using a standard
      technique, i.e. sampling on charcoal tubes and subsequent analysis by gas
      chromatography. Laboratory tests showed that the linearity of the answer of the
      PID is good for many compounds and for a mixture of these compounds. Similar
      tests were carried out for painters in workplaces with the same good correlations
      (determination coefficient r2 close to 1) between the PID response and the real
      concentration of the pollutants measured on the sampling tubes. The use of PID
      also allowed determination of the exposure profile of the workers and comparison
      of the short-term exposure to the corresponding limit values. Many cases of the
      short-term limit values being exceeded were revealed by use of the PID, although
      very few cases of the long-term limit values have been found by the usual
      sampling (charcoal tube) and analytical (gas chromatography) methods.

PMID- 14718350
TI  - Increased aortic stiffness: an unfavorable cardiorenal connection.

PMID- 14718351
TI  - Retinal expression of vascular endothelial growth factor is mediated by
      angiotensin type 1 and type 2 receptors.
AB  - Angiotensin II is a known stimulus for the expression of vascular endothelial
      growth factor (VEGF). This action of angiotensin II is mediated by the
      angiotensin type 1 (AT1) receptor. However, the role of the angiotensin type 2
      (AT2) receptor subtype in inducing VEGF expression has been controversial. The
      aim of the present study was to assess the effects of AT2 receptor blockade on
      VEGF expression in the retina, initially in experimental diabetic rats induced by
      injection of streptozotocin. The AT1 receptor antagonist, valsartan, or the AT2
      receptor antagonists, PD123319, were administered to diabetic rats for 4 weeks.
      Increased gene and protein expressions of VEGF, as assessed by real-time reverse
      transcription-polymerase chain reaction and immunostaining, respectively, were
      observed in the retina in diabetic rats. Treatment with either valsartan or
      PD123319 attenuated retinal VEGF expression. To further explore the link between
      angiotensin receptor subtypes and VEGF expression, valsartan, or PD123319 were
      administered to rats that were infused with angiotensin II for 2 weeks. VEGF
      expression was also increased in the retina from angiotensin II infused rats, and
      this was attenuated by valsartan and PD123319. These findings suggest that VEGF
      expression is modulated by AT1 and AT2 receptors, thereby implicating angiotensin
      II receptor subtypes in retinal diseases such as diabetic retinopathy.

PMID- 14718352
TI  - Blood pressure management in patients with acute ischemic stroke.

PMID- 14718353
TI  - Indicators of fetal growth do not independently predict blood pressure in 8-year
      old Australians: a prospective cohort study.
AB  - Inverse associations between size at birth and blood pressure (BP) in later life
      are commonly statistically significant only after adjustment for current size,
      consistent with change in size as the determinant. Few studies have been
      prospective or have included a range of potential confounders. Using regression
      models, including maternal and demographic variables, we examined associations
      between size at birth and BP in Australian children followed from week 16 of
      gestation to the age of 8 years. BP measurements were available from 1417
      children born after 37 weeks gestation without congenital abnormalities. In
      models adjusted only for sex, the birthweight (BW), birth length, ponderal index,
      head circumference, chest circumference, abdominal girth, mid-arm circumference,
      triceps skinfold, placental weight, or BW/placental weight ratio did not
      significantly predict SBP in 8-year-olds. With adjustment for current size,
      associations were inverse but not statistically significant (regression
      coefficients: BW, -1.11; 95% confidence limits [CL], -2.22, 0.01; birth length, 
      0.25; 95% CL, -0.52, 0.24) and remained nonsignificant after adjustment for
      confounders. Current weight, height, or body mass index significantly predicted
      SBP and DBP (P<0.001) with differences of 8/4 mm Hg between upper and lower
      quartiles; effects were similar in infants with lower and higher BW. These
      findings are consistent with postnatal change in size as the major determinant of
      BP in 8-year-olds and are important in the context of the worldwide "epidemic" of
      obesity in childhood as a likely precursor of increasing rates of hypertension in
      adults.

PMID- 14718354
TI  - Renal oxidative stress in medullary thick ascending limbs produced by elevated
      NaCl and glucose.
AB  - The effects of NaCl, glucose, and thyroid hormone on the production of superoxide
      (O2*-) within the renal medulla of Sprague-Dawley rats were examined. Responses
      of intracellular superoxide [O2*-]i in isolated medullary thick ascending limbs
      (mTALs) were studied using real-time fluorescent microscopy with measurement of
      the dehydroethidium (DHE) to ethidium (Eth) conversion ratio (Eth/DHE ratio
      unit). The results demonstrated that elevations of extracellular NaCl (from 152
      to 252 mmol/L), D-glucose (from 5 to 25 mmol/L), and triiodo-thyronine (T3; 10
      micromol/L) significantly increased [O2*-]i levels. Preincubation with superoxide
      scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (1 mmol/L) significantly
      inhibited these responses. Stimulation with equamolar amounts of choline chloride
      or L-glucose failed to increase [O2*]i, indicating that these O2*- responses were
      not determined by changes in osmolality. The responses to NaCl, D-glucose, and T3
      were abolished by pretreatment with the Na+/K+-ATPase pump inhibitor ouabain (4
      mmol/L) and with Na+/H+ -exchanger inhibitor dimethylamiloride (100 micromol/L).
      We conclude that elevations of extracellular NaCl, D-glucose, or T3 levels can
      activate both the Na+/K+-ATPase pump and Na+/H+ exchanger in mTAL, which, in
      turn, is associated with increased intracellular concentrations of superoxide.

PMID- 14718355
TI  - Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion.
AB  - Plasma levels of aldosterone are not always predictable from the activity of
      renin and the concentration of potassium. Among the unexplained are elevated
      levels of aldosterone in some obese humans. Obesity is characterized by increased
      plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids
      stimulate aldosteronogenesis. The most readily oxidized fatty acids are the
      polyunsaturated, and the most abundant of those is linoleic acid. We tested
      oxidized derivatives of linoleic acid for effects on rat adrenal cells. One
      derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was
      particularly potent. EKODE stimulated aldosteronogenesis at concentrations from
      0.5 to 5 micromol/L, and inhibited aldosteronogenesis at higher doses. EKODE's
      stimulatory effect was most prominent when angiotensin and potassium effects were
      submaximal. The lipid's mechanism of action was on the early pathway leading to
      pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma
      EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas
      tested contained EKODE in concentrations ranging from 10(-9) to 5x10(-7) mol/L.
      In samples from 24 adults, levels of EKODE correlated directly with aldosterone
      (r=0.53, P=0.007). In the 12 blacks in that cohort, EKODE also correlated with
      body mass index and systolic pressure. Those other correlations were not seen in
      white subjects. The results suggest that oxidized derivatives of polyunsaturated
      fatty acids other than arachidonic are biologically active. Compounds like EKODE,
      derived from linoleic acid, may affect adrenal steroid production in humans and
      mediate some of the deleterious effects of obesity and oxidative stress,
      especially in blacks.

PMID- 14718356
TI  - Relationship between carbamoyl-phosphate synthetase genotype and systemic
      vascular function.
AB  - Endothelial cells can convert l-citrulline to l-arginine, the precursor of nitric
      oxide. The present study tests the hypothesis that a C-to-A nucleotide
      transversion (T1405N) in the gene-encoding carbamoyl-phosphate synthetase 1, the
      enzyme catalyzing the rate-limiting step in l-citrulline formation, influences
      nitric oxide metabolite concentrations or nitric oxide-mediated vasodilation in
      humans. Bradykinin (100, 200, and 400 ng/min) was infused via brachial artery in
      106 (CC:AC:AA=40:54:12) healthy subjects. Sodium nitroprusside (1.6, 3.2, and 6.4
      microg/min) was also infused in 87 (CC:AC:AA=31:46:10) subjects. Forearm blood
      flow was measured by plethysmography and blood samples were collected for tissue
      type plasminogen activator antigen, nitric oxide metabolites, and cyclic GMP.
      There was a significant relationship between carbamoyl-phosphate synthetase 1
      genotype and nitric oxide metabolites, such that nitric oxide metabolite
      concentrations were highest in individuals homozygous for the C allele (mean+/
      SD, 14.0+/-8.5 micromol/L), lowest in individuals homozygous for the A allele
      (9.1+/-3.1 micromol/L), and intermediate (11.8+/-6.6 micromol/L) in heterozygotes
      (P=0.036). There was a significant effect of carbamoyl-phosphate synthetase 1
      genotype on forearm blood flow during bradykinin (P=0.028), such that the
      vasodilator response was greatest in C allele homozygotes (22.2+/-9.1 mL/min/100
      mL at 400 ng/min), least in A allele homozygotes (13.6+/-6.2 mL/min/100 mL), and
      intermediate (19.4+/-10.7 mL/min/100 mL) in heterozygotes. Similarly, carbamoyl
      phosphate synthetase 1 genotype influenced forearm blood flow during
      nitroprusside (maximal flow 19.2+/-8.3, 18.1+/-8.3, and 11.5+/-4.9 mL/min/100 mL
      in the CC:AC:AA groups, respectively; P=0.022). In contrast, there was no effect
      of carbamoyl-phosphate synthetase 1 genotype on the nitric oxide-independent
      tissue-type plasminogen activator response to bradykinin (P=0.943). These data
      indicate that a polymorphism in the gene encoding carbamoyl-phosphate synthetase
      1 influences nitric oxide production as well as vascular smooth muscle
      reactivity.

PMID- 14718357
TI  - Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A
      receptor-deficiency.
AB  - We previously showed that the phenotype of mice with targeted disruption of the
      gene encoding the AT1A receptor (Agtr1a), the major murine AT1 receptor isoform,
      is strongly influenced by recessive genetic modifiers derived from the C57BL/6 or
      129 inbred strains. To further evaluate the genetic modifiers on the C57BL/6
      background, we performed backcrosses between F1(C57BL/6x129) and C57BL/6 Agtr1a-/
      mice and analyzed the progeny, focusing on the development of structural lesions
      in the renal vasculature. In affected animals, these lesions are characterized by
      medial thickening of small arteries and arterioles in the kidney that are
      reminiscent of vascular lesions in patients with nephrosclerosis. Among 180
      consecutive progeny, 170 (94%) survived to completion of the study. On masked
      pathological examination at age 8 months, 86 had intermediate to severe vascular
      lesions whereas 84 had no detectable lesions. Based on a hypothetical model of a
      single recessive modifier locus arising from the C57BL/6 background, the observed
      proportion of affected animals among the backcross progeny was not statistically
      different from that predicted by chi2 analysis (51% versus 50%; P=0.88). We next
      performed genomic microsatellite analysis in a subset of 121 backcross progeny
      using a panel of markers spanning approximately 15 cM intervals across the mouse
      genome. By 2-point analysis, we found a region spanning 5 cM on chromosome 3,
      with significant linkage to the development of renal vascular lesions (LOD score:
      3.3 to 3.8).

PMID- 14718358
TI  - Production and role of extracellular guanosine cyclic 3', 5' monophosphate in
      sodium uptake in human proximal tubule cells.
AB  - The present study was designed to determine the capability of human renal
      proximal tubule (RPT) to generate and export guanosine cyclic 3', 5'
      monophosphate (cGMP) in response to direct stimulation of soluble guanylyl
      cyclase by nitric oxide (NO) donors. In addition, we investigated whether cGMP
      extrusion from human RPT cells is required for inhibition of cellular sodium
      uptake. RPT cells were cultured from fresh human kidneys (normotensive subjects,
      n=4, mean age 65+/-4.7 years, 3 men, 1 woman; hypertensive patients, n=6, mean
      age 64+/-6.1 years, 4 men, 2 women) after unilateral nephrectomy. The
      fluorescence dye Sodium Green was employed to determine cytoplasmic Na+
      concentration. In the presence of the Na+/K+ ATPase inhibitor ouabain,
      fluorescence was monitored at the appropriate wavelength (excitation 485 nm,
      emission 535 nm). Nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP, 10(
      4) M), increased both intracellular and extracellular cGMP (from 1.26+/-0.21 to
      88.7+/-12.6 pmol/mg protein and from 0.58+/-0.10 to 9.24+/-1.9 pmol/mL,
      respectively, P<0.01) and decreased cellular Na+ uptake by 37.4+/-6.8% (P<0.05)
      compared with control. The effects of SNAP on cGMP production were similar in
      normotensive and hypertensive subjects. The increases in intracellular and
      extracellular cGMP concentration because of SNAP were blocked completely by
      soluble guanylyl cyclase inhibitor ODQ (1-H-[1,2,4] oxadiazolo [4,2-alpha]
      quinoxalin-1-one). Probenecid, an organic anion transport inhibitor, augmented
      the SNAP (10(-6) M)-induced increase in intracellular cGMP accumulation (from
      4.9+/-0.9 to 9.8+/-1.5 pmol/mg protein, P<0.05), abrogated the SNAP-induced
      increase in extracellular cGMP extrusion (from 1.07+/-0.4 to 0.37+/-0.1 pmol/L,
      P<0.05) and blocked the SNAP-induced reduction in cellular Na+ uptake. Neither
      intracellular nor extracellular cGMP were influenced by l-arginine, the metabolic
      precursor of NO, or N(G)-nitro-L-arginine methyl ester, an inhibitor of NO
      synthase. After exogenous administration of cGMP (10(-5) M) or its membrane
      permeable analogue 8-Br-cGMP (10(-5) M), only 8-Br-cGMP crossed the cell membrane
      to increase intracellular cGMP (from 1.36+/-0.19 to 289.7+/-29.4 pmol/mg protein,
      P<0.01). However, both cGMP and 8-Br-cGMP were effective in decreasing cellular
      Na+ uptake. In conclusion, human RPT cells contain soluble guanylyl cyclase and
      are able to generate and export cGMP in response to NO. Because human RPT cells
      do not themselves contain constitutive NO synthase, the NO-generating cGMP must
      be derived from sources outside the human RPT. The cGMP cellular export system is
      critical in the regulation of RPT cellular Na+ absorption in humans.

PMID- 14718359
TI  - Heritability of leukoaraiosis in hypertensive sibships.
AB  - Ischemic damage to the subcortical white matter of the brain, referred to as
      leukoaraiosis, is a frequent complication of hypertension-related microvascular
      disease and contributes to the risk of stroke and vascular dementia. A large
      genetic contribution to this late-life form of target organ damage was suggested
      by a study of elderly male twins. As part of the Genetic Epidemiology Network of
      Arteriopathy (GENOA), 483 non-Hispanic white subjects were recruited to undergo
      MRI for determination of the brain volume of leukoaraiosis (291 women and 192 men
      from 210 sibships providing 434 sibling pairs; mean age+/-SD=65.2+/-7.3 years).
      The GENOA-Rochester sibships contain 2 or more siblings with essential
      hypertension diagnosed before age 60. The frequency distribution of the volume of
      leukoaraiosis was positively skewed, with a median value of 6.61 cm3
      (interquartile range: 4.77 to 9 0.83 cm3). Variance component models were used to
      estimate the heritability (ie, the proportion of phenotypic variation caused by
      additive genetic factors). After logarithm transformation of the volume of
      leukoaraiosis, the estimated heritability (+/-SE) was 0.802+/-0.102 (P<0.0001).
      Adjustments for sex, age, systolic blood pressure, and brain volume reduced the
      heritability estimate to 0.671+/-0.110 (P<0.0001). This evidence of strong
      genetic influence on the susceptibility to leukoaraiosis justifies efforts to
      localize the responsible genes and characterize the predisposing genetic
      polymorphisms.

PMID- 14718360
TI  - Role for thromboxane receptors in angiotensin-II-induced hypertension.
AB  - To evaluate the role of thromboxane in hypertension and its complications, we
      studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin
      II-dependent model of hypertension. To determine whether genetic background might
      alter the physiological actions of the TP receptor, we studied two lines of TP
      knockout (Tp-/-) mice with distinct genetic backgrounds (C57BL/6 and BALB/c).
      During chronic angiotensin II infusion (1000 ng/kg per minute x 28 days by
      subcutaneous osmotic pump), TP deficiency prevented mortality in the C57BL/6
      background but not in the BALB/c strain. Chronic angiotensin II infusion also
      caused a rapid and significant increase in blood pressure in wild-type (WT)
      C57BL/6 and BALB/c animals, which was significantly attenuated in Tp-/- mice on
      either background. After 28 days of infusion, cardiac hypertrophy only occurred
      in the C57BL/6 strain: heart/body weight ratio increased by 57%+/-8% in WT mice
      compared with 17%+/-6.5% for the Tp-/- mice (P<0.01). Chronic angiotensin II
      infusion caused albuminuria only in the C57BL/6 strain, and TP deficiency did not
      alter its development. Cyclooxygenase-1 knockout mice also had attenuated blood
      pressure increase during chronic angiotensin II infusion, suggesting that
      cyclooxygenase-1 metabolites are involved in angiotensin-II-dependent
      hypertension. Thus, on the C57BL/6 background, TP receptors contribute to cardiac
      hypertrophy but not proteinuria. However, irrespective of genetic background, the
      TP receptor makes a robust contribution to the pathogenesis of angiotensin II
      dependent hypertension.

PMID- 14718362
TI  - Long-term antioxidant intervention improves myocardial microvascular function in
      experimental hypertension.
AB  - Hypertension increases oxidative stress, which can impair myocardial
      microvascular function and integrity. However, it is yet unclear whether long
      term antioxidant intervention in early hypertension would preserve myocardial
      perfusion and vascular permeability responses to challenge. Pigs were studied
      after 12 weeks of renovascular hypertension without (n=8) or with daily
      supplementation of antioxidants (100 IU/kg vitamin E and 1 g vitamin C, n=6), and
      compared with normal controls (n=7). Myocardial perfusion and microvascular
      permeability were measured in vivo by electron beam computed tomography before
      and after 2 cardiac challenges (intravenous adenosine and dobutamine). Basal left
      ventricular muscle mass was also obtained. Mean arterial pressure was
      significantly increased in both groups of hypertensive animals (without and with
      antioxidants, 123+/-9 and 126+/-4 mm Hg, respectively, versus normal, 101+/-4 mm
      Hg; both P<0.05), but muscle mass was not different among the groups. The
      impaired myocardial perfusion response to adenosine observed in hypertensives
      (normal, +51+/-14%; P<0.05 versus baseline; hypertension, +14+/-15%; P=0.3 versus
      baseline) was preserved in hypertensive pigs that received antioxidants (+44+/
      15%; P=0.01 compared with baseline). Long-term antioxidant intervention also
      preserved subendocardial microvascular permeability responses in hypertension. On
      the other hand, antioxidant intervention had little effect on the hypertension
      induced myocardial vascular dysfunction observed in response to dobutamine. This
      study demonstrates that the impaired myocardial perfusion and permeability
      responses to increased cardiac demand in early hypertension are significantly
      improved by long-term antioxidant intervention. These results support the
      involvement of oxidative stress in myocardial vascular dysfunction in
      hypertension and suggest a role for antioxidant strategies to preserve the
      myocardial microvasculature.

PMID- 14718363
TI  - Rosiglitazone restores G-protein coupling, recruitment, and function of renal
      dopamine D1A receptor in obese Zucker rats.
AB  - Hypertension related to insulin resistance results from increased sodium
      retention. Dopamine, by activating D1A receptors in renal proximal tubules,
      increases sodium excretion. Recently, dopamine has been shown to augment its own
      signaling by recruiting intracellular D1A receptors to cell surface in proximal
      tubules. In this study, we hypothesized that coupling of D1A receptors to G
      proteins and dopamine-induced recruitment of D1A receptors to the plasma membrane
      are impaired in obese Zucker rats, resulting in a diminished natriuretic and
      diuretic response to D1A receptor agonist, SKF-38393. We also examined effects of
      rosiglitazone (3 mg/kg per day, 15 days) in restoring the defects in D1A receptor
      signaling and function in these animals. In obese rats, D1A receptors did not
      couple to G proteins, as shown by a lack of fenoldopam-sensitive [35S] GTPgammaS
      binding. In addition, we observed, by using radioligand binding and
      immunoblotting, that dopamine recruited D1A receptors to cell surface in lean
      Zucker rats but failed to do so in obese rats. Rosiglitazone treatment resulted
      in restoration of G-protein coupling of D1A receptors and their recruitment by
      dopamine in obese rats similar to that seen in lean rats. Furthermore, SKF-38393
      failed to increase natriuresis and diuresis in obese rats compared with lean
      rats. However, in rosiglitazone-treated obese rats, SKF-38393 elicited a diuretic
      and natriuretic response similar to that in lean rats. Collectively, these
      results suggest that insulin resistance may be responsible for impaired renal
      dopamine D1A receptor signaling and function as treatment with an insulin
      sensitizer, rosiglitazone, normalizes these parameters in obese Zucker rats.

PMID- 14718364
TI  - Dietary NaCl regulates renal aminopeptidase N: relevance to hypertension in the
      Dahl rat.
AB  - Aminopeptidase N (APN) is an abundant metallohydrolase in the brush border of
      kidney proximal tubule cells that degrades angiotensin III (Ang III) to
      angiotensin IV (Ang IV) and, along with dipeptidylaminopeptidase, degrades Ang
      IV. We examined the impact of a high-salt diet on renal APN activity and
      transcript abundance in the Sprague-Dawley and Dahl salt-sensitive (SS/Jr) rat
      strains. APN transcript abundance and protein abundance were approximately 2-fold
      greater (P<0.05; n=6) in the kidneys of Sprague-Dawley and Lewis rats ingesting
      8% versus 0.3% salt diets, suggesting that increased aminopeptidase activity may
      contribute to decreased renal sodium uptake during adaptation to a high-salt
      diet. In contrast, renal APN transcript abundance and activity were the same in
      Dahl SS/Jr rats ingesting 8.0% versus 0.3% salt diets. The APN gene was mapped,
      using a radiation-hybrid panel, to known quantitative loci on chromosome 1 for
      blood pressure in the Dahl SS/Jr rat. The results suggest that the APN gene is a
      good candidate for salt-sensitivity in the Dahl SS/Jr rat.

PMID- 14718366
TI  - Assessment of renal functional phenotype in mice lacking gp91PHOX subunit of
      NAD(P)H oxidase.
AB  - To determine the role of endogenous superoxide (O2-) in the kidney, we assessed
      renal hemodynamics and excretory function in gp91(PHOX) (a NAD(P)H oxidase
      subunit) gene knockout (KO) mice and compared these findings with those of wild
      type (WT) strain C57BL/6 mice. Renal blood flow (RBF) and glomerular filtration
      rate (GFR) were determined by PAH and inulin clearances respectively in
      anesthetized mice (n=8 in each group). There were higher baseline RBF (4.3+/-0.4
      versus 2.5+/-0.2 mL/min per gram; P<0.002) and lower renal vascular resistance
      (RVR) (16+/-1.4 versus 29+/-2.3 mm Hg/mL/min per gram; P<0.0001) in KO compared
      with WT without a significant difference in mean arterial pressure (MAP) (67+/-2
      versus 71+/-2 mm Hg) and GFR (0.66+/-0.09 versus 0.73+/-0.05 mL/min per gram)
      between the strains. Intravenous infusion of angiotensin II (Ang II) (2 ng/min
      per gram of body weight) for 30 minutes caused a lesser degree of decreases in
      RBF (-8% versus -33%) and of increases in RVR (+73% versus +173%) in KO compared
      with WT. GFR was increased (43%) in KO but not in WT during Ang II infusion.
      Urinary excretion of nitrate/nitrite was higher in conscious KO (n=5) than in WT
      (n=5), indicating an increase in nitric oxide bioavailability that could be the
      cause of high RBF and low RVR in KO. These data indicate that gp91(PHOX), a
      subunit of NAD(P)H oxidase, plays a regulatory role in the maintenance of renal
      vascular tone. These results also suggest that the mechanism of Ang II-mediated
      renal vascular action involves concomitant generation of O2-.

PMID- 14718367
TI  - Role of platelet microparticles in the production of thromboxane by rabbit
      pulmonary artery.
AB  - This study examined the role of platelet microparticles in thromboxane A2 (TXA2)
      production. Incubation of microparticles with [14C]arachidonic acid and A23187
      produced 14C-labeled TXB2, the stable metabolite of TXA2. To investigate the
      possibility that endothelial cells (ECs) transfer arachidonic acid to platelet
      microparticles and promote TXB2 synthesis, ECs with their cellular lipids
      prelabeled with tritiated arachidonic acid were incubated with microparticles. In
      the absence of microparticles, there was no production of tritiated TXB2 by the
      ECs. However, when microparticles were coincubated with prelabeled ECs, tritiated
      arachidonic acid was metabolized to tritiated TXB2. Aspirin was then used to
      inhibit cyclooxygenase. ECs coincubated with aspirin-treated platelet
      microparticles did not produce TXB2, as measured by radioimmunoassay. In
      contrast, aspirin-treated ECs coincubated with microparticles produced TXB2, and
      its production was enhanced by methacholine (10(-4) mol/L), indicating that
      endothelially derived arachidonic acid, and not endothelially derived
      prostaglandin endoperoxide, was transferred to the microparticle and further
      metabolized to TXA2. Additional studies with rabbit aorta and pulmonary artery
      investigated whether microparticles contributed to vascular contractions.
      Preincubation with microparticles enhanced arachidonic acid-induced contractions
      in the aorta and methacholine-induced contractions in the pulmonary artery. The
      thromboxane receptor antagonist SQ29548 and the thromboxane synthase inhibitor
      dazoxiben blocked these effects. Because TXA2 is an important mediator in various
      pathophysiologic states, including hypertension, the ability of platelet
      microparticles to act as a cellular source of TXA2 might provide new insight into
      the role of platelets and platelet microparticles in the control of vascular
      tone.

PMID- 14718368
TI  - Heterogeneity of cardiorenal characteristics in normotensive subjects.
AB  - Blood pressure is a marker of elevated risk for cardiovascular disease, even
      within the normotensive range. The present study evaluates cardiorenal
      modifications observed in normotensive (<140/90 mm Hg) subjects. Using World
      Health Organization-International Society of Hypertension definitions, 265
      normotensive subjects were categorized as having optimal (n=73), normal (n=84),
      and high-normal (n=108) blood pressure. Renal hemodynamics and function and
      cardiac morphology were evaluated by isotopic clearance techniques and
      ultrasonography, respectively. Urinary albumin excretion was measured in 24-hour
      urine collections. Body mass index and 24-hour urinary sodium (estimate of sodium
      intake), as well as left ventricular mass index, relative wall thickness, and
      glomerular filtration rate and filtration fraction, progressively increased in
      the optimal to high-normal groups. In contrast, effective renal plasma flow
      remained constant. Albuminuria was similar in all groups. Of interest, the
      proportion of subjects with concentric pattern of cardiac geometry (relative wall
      thickness > or =0.44) increased from 7% in optimal to 13% and 20% in normal and
      high-normal groups, respectively (P<0.05). Within this normotensive range of
      blood pressure, left ventricular mass index and relative wall thickness but not
      albuminuria were linearly correlated to systolic blood pressure; however, no
      correlation with diastolic blood pressure was found. In conclusion, changes in
      cardiac geometry and renal hemodynamics (increase in glomerular filtration rate
      and filtration fraction, an approximate index of glomerular pressure) that could
      predispose to cardiovascular morbidity and renal risk are already present in
      normotensive subjects with blood pressure higher than 120/80 mm Hg.

PMID- 14718369
TI  - Tumor attenuation by 2(6-hydroxynaphthyl)-beta-D-xylopyranoside requires priming
      of heparan sulfate and nuclear targeting of the products.
AB  - We have previously reported that the heparan sulfate-priming glycoside 2-(6
      hydroxynaphthyl)-beta-D-xylopyranoside selectively inhibits growth of transformed
      or tumor-derived cells. To investigate the specificity of this xyloside various
      analogs were synthesized and tested in vitro. Selective growth inhibition was
      dependent on the presence of a free 6-hydroxyl in the aglycon. Because cells
      deficient in heparan sulfate synthesis were insensitive to the xyloside, we
      conclude that priming of heparan sulfate synthesis was required for growth
      inhibition. In growth-inhibited cells, heparan sulfate chains primed by the
      active xyloside were degraded to products that contained anhydromannose and
      appeared in the nuclei. Hence the degradation products were generated by nitric
      oxide-dependent cleavage. Accordingly, nitric oxide depletion reduced nuclear
      localization of the degradation products and counteracted the growth-inhibitory
      effect of the xyloside. We propose that 2-(6-hydroxynaphthyl)-beta-D
      xylopyranoside entered cells and primed synthesis of heparan sulfate chains that
      were subsequently degraded by nitric oxide into products that accumulated in the
      nucleus. In vivo experiments demonstrated that the xyloside administered
      subcutaneously, perorally, or intraperitoneally was adsorbed and made available
      to tumor cells located subcutaneously. Treatment with the xyloside reduced the
      average tumor load by 70-97% in SCID mice. The present xyloside may serve as a
      lead compound for the development of novel antitumor strategies.

PMID- 14718370
TI  - C-Mannosylation of MUC5AC and MUC5B Cys subdomains.
AB  - We expressed recombinant Cys subdomains in COS-7 cells to examine the role of
      this highly conserved protein domain in mucin biosynthesis. The entire Cys1 and
      Cys5 and Cys1 and Cys3 subdomains in MUC5AC and MUC5B, respectively, each with
      six carboxyl terminal histidine residues, were pulse-labeled with
      [(35)S]cysteine/methionine, and the labeled proteins were examined in the culture
      medium. Under nonreducing conditions, secreted Cys subdomains were monomers,
      indicating the absence of interchain disulfide bonds. Cross-linking studies
      suggested the domains are able to interact through very weak noncovalent
      interactions. Though the domains had apparent M(r) consistent with the absence of
      N- and O-glycans, they could be purified with mannose-specific lectins. Lectin
      binding was prevented by mutation of the first tryptophan residue in the putative
      C-mannosylation acceptor motif WXXW, indicating that C-mannosylation is
      responsible for lectin binding. As judged by pulse-chase experiments, C
      mannosylation occurred very early during the domain biosynthesis, likely in the
      endoplasmic reticulum (ER). Mutation of the WXXW motif or expression of the
      unmutated domain in CHO-Lec35.1 cells, a C-mannosylation-defective cell line,
      resulted in reduced secretion of the corresponding Cys subdomains. Live cell
      imaging of green fluorescent protein fused to the Cys subdomains clearly revealed
      increased presence of Cys subdomains in the ER of CHO-Lec35.1 cells when compared
      to the same domains expressed in CHO-K1 cells. Considered together, these studies
      suggest that the Cys subdomains of MUC5AC and MUC5B are C-mannosylated in their
      respective WXXW motifs. C-mannosylation is likely required for proper folding of
      the Cys subdomains and/or for some aspect of ER export during mucin biosynthesis.

PMID- 14718371
TI  - Accumulation of high-molecular-weight amylose in Alzheimer's disease brains.
AB  - Although most of the glucose metabolized in the brain is taken up from the blood,
      glucose derived from glycogen stores is increasingly implicated in both normal
      brain function and injury repair. An impaired glucose metabolism is one of the
      features of Alzheimer's disease (AD) entailing a reduction in glucose
      transporters and the uptake of glucose as well as alterations in the specific
      activity of glycolytic enzymes. Here we report that AD brains accumulate amylose,
      the unbranched alpha(1,4)-linked glucose polymer that is resistant to degradation
      by glycolytic enzymes. Neutral polysaccharides harvested from postmortem brains
      were purified with hydrazinolysis, ion exchange, and sizing chromatography and
      subjected to NMR spectroscopy, GC, GC-MS, and methylation analysis. Five percent
      of the polysaccharides (50 micro g [0.3 micro mol]/g wet weight brain tissue)
      consisted of amylose with molecular weights exceeding 600,000 Da. There is no
      evidence for 1,6-branching, indicating that the polymer is not a form of high
      molecular-weight glycogen. By GC analysis, the glucose content of the AD brains
      was almost three times greater than that of the age-matched control brains. A
      synthesis of amylose in AD brains at the expense of glycogen would compromise
      glucose metabolism and enhance neural degeneration.

PMID- 14718372
TI  - Synthesis of a novel photoaffinity derivative of 1-deoxynojirimycin for active
      site-directed labeling of glucosidase I.
AB  - Glucosidase I releases the distal alpha1,2-glucosyl residue in the
      Glc(3)Man(9)GlcNAc(2) precursor immediately after its transfer from the dolichol
      P-P-linked intermediate in the endoplasmic reticulum and triggers the processes
      for the posttranslational remodeling, folding, and maturation of N-linked
      glycoproteins. The enzyme has been purified and characterized from several
      eukaryotic systems. Its cDNA and the gene have also been cloned. The enzyme is a
      target for the development of drugs for several pathological conditions. A
      structural analysis on the biochemically purified enzyme has been hampered
      because of its low abundance and unstable character. The recombinant enzyme has
      not been obtained in quantity and characterized. Glucosidase I is strongly
      inhibited by the glucose analog 1-deoxynojirimycin (DNM). To gain an insight into
      the architecture of the active site of the enzyme, we here report the synthesis
      of a photoactive derivative of DNM, viz. 4-(rho-azidosalicylamido)butyl-5-amido
      pentyl-1-DNM (ASBA-P-DNM). With an IC(50) of 0.42 micro M, it is nearly nine
      times stronger inhibitor than DNM (IC(50) = 3.5 micro M). On photolysis, the
      bound [(125)I]ASBA-P-DNM specifically labels the native enzyme, which yields a 24
      kDa peptide after treatment with V8 protease, apparently representing the region
      around its active site. Thus ASBA-P-DNM should serve as a novel reagent to
      conduct structure-function analysis on glucosidase I.

PMID- 14718373
TI  - Glycosaminoglycan degradation fragments in mucopolysaccharidosis I.
AB  - The catabolism of glycosaminoglycans begins with endohydrolysis of
      polysaccharides to oligosaccharides followed by the sequential action of an array
      of exoenzymes to reduce these oligosaccharides to monosaccharides and inorganic
      sulfate. In a lysosomal storage disorder known as mucopolysaccharidosis I, caused
      by a deficiency of the exohydrolase alpha-l-iduronidase, fragments of two
      different glycosaminoglycans, dermatan sulfate and heparan sulfate, have been
      shown to accumulate. Oligosaccharides isolated from the urine of a
      mucopolysaccharidosis I patient using anion exchange and gel filtration
      chromatography were identified as di-, tri-, tetra-, penta-, and hexasaccharides
      using electrospray ionization-tandem mass spectrometry and shown to have
      nonreducing terminal alpha-l-iduronate residues, susceptible to digestion with
      alpha-l-iduronidase. The presence of odd and even oligosaccharides suggests both
      endo-beta-glucuronidase and endo-N-acetylhexosaminidase activities toward both
      glycosaminoglycans. Cultured skin fibroblasts from mucopolysaccharidosis I
      patients accumulate the same dermatan sulfate-and heparan sulfate-derived di- and
      trisaccharides as identified in urine, and supplementation of culture medium with
      recombinant alpha-l-iduronidase reduced their level to that of unaffected control
      fibroblasts. A dermatan-derived tetrasaccharide not elevated in
      mucopolysaccharidosis I fibroblasts transiently increased in these fibroblasts in
      the presence of recombinant alpha-l-iduronidase, indicating it is an intermediate
      product of catabolism. These oligosaccharides were elevated in urine samples from
      mucopolysaccharidosis I patients, and we suggest that these glycosaminoglycan
      derived oligosaccharides may be useful biochemical markers for the identification
      and the clinical management of mucopolysaccharidosis I patients.

PMID- 14718374
TI  - Interactions of heparin/heparan sulfate with proteins: appraisal of structural
      factors and experimental approaches.
AB  - Over the past decade, the glycosaminoglycans heparin and heparan sulfate have
      been shown to bind and regulate the activities of many proteins. Established
      techniques have provided both qualitative and quantitative information regarding
      these interactions, leading to a general view that proteins bind with a variety
      of affinities to particular sequences within heparin or heparan sulfate chains.
      The mechanism by which heparan sulfate regulates the activity of proteins through
      such interactions has, however, proved more elusive. We survey some relevant
      details of the structural characteristics of heparin/heparan sulfate and the
      approaches used to investigate their interactions with proteins. For the latter,
      the interactions of heparin/heparan sulfate with fibroblast growth factors and
      their receptors will be emphasized, because these proteins have been the subject
      of many studies. We reflect on the information that various techniques have
      provided, points regarding their use, and some relevant theoretical
      considerations regarding the study of protein-heparin/heparan sulfate
      interactions. A perspective of new and developing approaches, which may aid
      advances in this field, is also provided.

PMID- 14718375
TI  - Structure/function study of Lewis alpha3- and alpha3/4-fucosyltransferases: the
      alpha1,4 fucosylation requires an aromatic residue in the acceptor-binding
      domain.
AB  - All vertebrate alpha3- and alpha3/4-FUTs possess the characteristic acceptor
      binding motif VxxHH(W/R)(D/E). FUT6 and FUTb enzymes, harboring R in the acceptor
      binding motif, transfer fucose in alpha1,3 linkage, whereas FUT3 and FUT5 enzymes
      with W at the candidate position can also transfer fucose in alpha1,4 linkage
      FUT3 being more efficient than FUT5. To determine the involvement of the W/R
      residue in acceptor recognition, we produced 34 variants of human FUT3, FUT5,
      FUT6, and ox FUTb Lewis enzymes. Among the FUT3 variants where W(111) was
      replaced by the other amino acids, only enzymes with an aromatic residue at the
      candidate position kept about 50% of alpha1,4 activity and showed no changes in
      K(m) values for GDP-Fuc donor and H-type 1 acceptor substrates. All other
      substitutions produced enzymes with less than 20% of the alpha1,4 activity. Thus
      the ability of alpha3/4-FUTs to recognize type 1 substrates involves the aromatic
      character of W in the acceptor-binding domain. The alpha1,3 activity of FUT6 and
      FUTb significantly decreased when their R residue was substituted by basic or
      charged residues. Moreover, FUT3 and FUT5 variants with W-->R substitution had a
      better affinity for H-type 2 substrate and higher alpha1,3 activities. Therefore
      the optimal fucose addition in alpha1,3 linkage requires the R residue in the
      acceptor-binding motif of Lewis FUTs.

PMID- 14718376
TI  - A BAC- and BIBAC-based physical map of the soybean genome.
AB  - Genome-wide physical maps are crucial to many aspects of advanced genome
      research. We report a genome-wide, bacterial artificial chromosome (BAC) and
      plant-transformation-competent binary large-insert plasmid clone (hereafter
      BIBAC)-based physical map of the soybean genome. The map was constructed from
      78001 clones from five soybean BAC and BIBAC libraries representing 9.6 haploid
      genomes and three cultivars, and consisted of 2905 BAC/BIBAC contigs, estimated
      to span 1408 Mb in physical length. We evaluated the reliability of the map
      contigs using different contig assembly strategies, independent contig building
      methods, DNA marker hybridization, and different fingerprinting methods, and the
      results showed that the contigs were assembled properly. Furthermore, we tested
      the feasibility of integrating the physical map with the existing soybean
      composite genetic map using 388 DNA markers. The results further confirmed the
      nature of the ancient tetraploid origin of soybean and indicated that it is
      feasible to integrate the physical map with the linkage map even though greater
      efforts are needed. This map represents the first genome-wide, BAC/BIBAC-based
      physical map of the soybean genome and would provide a platform for advanced
      genome research of soybean and other legume species. The inclusion of BIBACs in
      the map would streamline the utility of the map for positional cloning of genes
      and QTLs, and functional analysis of soybean genomic sequences.

PMID- 14718377
TI  - Analysis of multiple genomic sequence alignments: a web resource, online tools,
      and lessons learned from analysis of mammalian SCL loci.
AB  - Comparative analysis of genomic sequences is becoming a standard technique for
      studying gene regulation. However, only a limited number of tools are currently
      available for the analysis of multiple genomic sequences. An extensive data set
      for the testing and training of such tools is provided by the SCL gene locus.
      Here we have expanded the data set to eight vertebrate species by sequencing the
      dog SCL locus and by annotating the dog and rat SCL loci. To provide a resource
      for the bioinformatics community, all SCL sequences and functional annotations,
      comprising a collation of the extensive experimental evidence pertaining to SCL
      regulation, have been made available via a Web server. A Web interface to new
      tools specifically designed for the display and analysis of multiple sequence
      alignments was also implemented. The unique SCL data set and new sequence
      comparison tools allowed us to perform a rigorous examination of the true
      benefits of multiple sequence comparisons. We demonstrate that multiple sequence
      alignments are, overall, superior to pairwise alignments for identification of
      mammalian regulatory regions. In the search for individual transcription factor
      binding sites, multiple alignments markedly increase the signal-to-noise ratio
      compared to pairwise alignments.

PMID- 14718379
TI  - Flux coupling analysis of genome-scale metabolic network reconstructions.
AB  - In this paper, we introduce the Flux Coupling Finder (FCF) framework for
      elucidating the topological and flux connectivity features of genome-scale
      metabolic networks. The framework is demonstrated on genome-scale metabolic
      reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces
      cerevisiae. The analysis allows one to determine whether any two metabolic
      fluxes, v(1) and v(2), are (1) directionally coupled, if a non-zero flux for v(1)
      implies a non-zero flux for v(2) but not necessarily the reverse; (2) partially
      coupled, if a non-zero flux for v(1) implies a non-zero, though variable, flux
      for v(2) and vice versa; or (3) fully coupled, if a non-zero flux for v(1)
      implies not only a non-zero but also a fixed flux for v(2) and vice versa. Flux
      coupling analysis also enables the global identification of blocked reactions,
      which are all reactions incapable of carrying flux under a certain condition;
      equivalent knockouts, defined as the set of all possible reactions whose deletion
      forces the flux through a particular reaction to zero; and sets of affected
      reactions denoting all reactions whose fluxes are forced to zero if a particular
      reaction is deleted. The FCF approach thus provides a novel and versatile tool
      for aiding metabolic reconstructions and guiding genetic manipulations.

PMID- 14718380
TI  - Closing the gaps on human chromosome 19 revealed genes with a high density of
      repetitive tandemly arrayed elements.
AB  - The reported human genome sequence includes about 400 gaps of unknown sequence
      that were not found in the bacterial artificial chromosome (BAC) and cosmid
      libraries used for sequencing of the genome. These missing sequences correspond
      to approximately 1% of euchromatic regions of the human genome. Gap filling is a
      laborious process because it relies on analysis of random clones of numerous
      genomic BAC or cosmid libraries. In this work we demonstrate that closing the
      gaps can be accelerated by a selective recombinational capture of missing
      chromosomal segments in yeast. The use of both methodologies allowed us to close
      the four remaining gaps on the human chromosome 19. Analysis of the gap sequences
      revealed that they contain several abnormalities that could result in instability
      of the sequences in microbe hosts, including large blocks of micro- and
      minisatellites and a high density of Alu repeats. Sequencing of the gap regions,
      in both BAC and YAC forms, allowed us to generate a complete sequence of four
      genes, including the neuronal cell signaling gene SCK1/SLI. The SCK1/SLI gene
      contains a record number of minisatellites, most of which are polymorphic and
      transmitted through meiosis following a Mendelian inheritance. In conclusion, the
      use of the alternative recombinational cloning system in yeast may greatly
      accelerate work on closing the remaining gaps in the human genome (as well as in
      other complex genomes) to achieve the goal of annotation of all human genes.

PMID- 14718378
TI  - Expression profiling and comparative genomics identify a conserved regulatory
      region controlling midline expression in the zebrafish embryo.
AB  - Differential gene transcription is a fundamental regulatory mechanism of
      biological systems during development, body homeostasis, and disease. Comparative
      genomics is believed to be a rapid means for the identification of regulatory
      sequences in genomes. We tested this approach to identify regulatory sequences
      that control expression in the midline of the zebrafish embryo. We first isolated
      a set of genes that are coexpressed in the midline of the zebrafish embryo during
      somitogenesis stages by gene array analysis and subsequent rescreens by in situ
      hybridization. We subjected 45 of these genes to Compare and DotPlot analysis to
      detect conserved sequences in noncoding regions of orthologous loci in the
      zebrafish and Takifugu genomes. The regions of homology that were scored in
      nonconserved regions were inserted into expression vectors and tested for their
      regulatory activity by transient transgenesis in the zebrafish embryo. We
      identified one conserved region from the connective tissue growth factor gene
      (ctgf), which was able to drive expression in the midline of the embryo. This
      region shares sequence similarity with other floor plate/notochord-specific
      regulatory regions. Our results demonstrate that an unbiased comparative approach
      is a relevant method for the identification of tissue-specific cis-regulatory
      sequences in the zebrafish embryo.

PMID- 14718381
TI  - Buried alive: a novel approach to cancer treatment.
AB  - The heightened interest in the development of novel anti-cancer drugs that
      trigger apoptotic death in cancer cells stems from the fact that immediately upon
      execution of the death signal, the corpse is efficiently removed via specific
      recruitment of phagocytic cells. This prevents spilling of cellular contents and
      the associated inflammatory response, a likely scenario during necrotic death.
      Recent evidence has established that phagocytic removal of apoptotic cells is a
      function of ligand-receptor interaction, whereby the ligand(s) for the scavenger
      receptor(s) of phagocytic cells is/are specifically expressed on apoptosing
      cells. Therefore, by implication, enhancing this ligand-receptor interaction
      could be an alternate means for removing unwanted cells. Here we present a
      provocative hypothesis that circumvents the need for chemotherapy-induced
      apoptosis in cancer cells. According to our model, cancer cells need not die in
      order to be removed by scavenger cells, but could still be effectively
      phagocytosed provided the cell surface expression of specific molecules that
      strongly engage phagocytic cells is sufficiently enhanced. In other words,
      inducing the expression of "eat me" signals on cancer cells could be a novel
      approach to "bury alive" these unwanted cells without the untoward effects of
      chemotherapy-induced apoptosis.

PMID- 14718382
TI  - Polo-like kinase (Plk) 1: a novel target for the treatment of prostate cancer.
AB  - Second only to skin cancer, cancer of the prostate gland (CaP) is the most
      commonly occurring cancer in American men. Existing treatment approaches and
      surgical intervention have been unable to effectively manage this dreaded cancer;
      therefore, efforts are ongoing to explore novel targets and strategies for the
      management of CaP. A complete understanding of the genetic control of the
      processes of cellular proliferation and programmed cell death, or "apoptosis,"
      may provide the basis for the rational design of novel therapeutic strategies
      against CaP. Key regulators for the mitotic progression in mammalian cells are
      the polo-like kinases (Plks). The activity of Plk1 is elevated in tissues and
      cells with a high mitotic index, including cancer cells. An increasing body of
      evidence suggests that the level of Plk1 expression has prognostic value for
      predicting outcomes in patients with some cancers such as lung cancer, squamous
      cell carcinomas of the head and neck, melanomas, and ovarian and endometrial
      carcinomas. However, the role of Plk1 in CaP is not known. Here, a hypothesis is
      put forward that Plk 1 plays a critical role in the development of prostate
      cancer; and the silencing of Plk1 will result in elimination of human CaP cells
      via an inactivation of cyclin-dependent kinase 1 (Cdc2)/cyclin B 1-mediated
      mitotic arrest followed by apoptosis. A corollary to this hypothesis is that Plk1
      could serve as a target for the intervention of CaP in humans. Therefore, if the
      hypothesis is tested to be true, it is conceivable that gene therapeutic
      approaches aimed at Plk1 or the pharmacological inhibitors of Plk1 may be
      developed for the treatment/management of CaP.

PMID- 14718383
TI  - A genomic perspective on protein tyrosine phosphatases: gene structure,
      pseudogenes, and genetic disease linkage.
AB  - The protein tyrosine phosphatases (PTPs) are now recognized as critical
      regulators of signal transduction under normal and pathophysiological conditions.
      In this analysis we have explored the sequence of the human genome to define the
      composition of the PTP family. Using public and proprietary sequence databases,
      we discovered one novel human PTP gene and defined chromosomal loci and exon
      structure of the additional 37 genes encoding known PTP transcripts. Direct
      orthologs were present in the mouse genome for all 38 human PTP genes. In
      addition, we identified 12 PTP pseudogenes unique to humans that have probably
      contaminated previous bioinformatics analysis of this gene family. PCR
      amplification and transcript sequencing indicate that some PTP pseudogenes are
      expressed, but their function (if any) is unknown. Furthermore, we analyzed the
      enhanced diversity generated by alternative splicing and provide predicted amino
      acid sequences for four human PTPs that are currently defined by fragments only.
      Finally, we correlated each PTP locus with genetic disease markers and identified
      4 PTPs that map to known susceptibility loci for type 2 diabetes and 19 PTPs that
      map to regions frequently deleted in human cancers. We have made our analysis
      available at http://ptp.cshl.edu or http://science.novonordisk.com/ptp and we
      hope this resource will facilitate the functional characterization of these key
      enzymes.

PMID- 14718384
TI  - Quality control of MHC class I maturation.
AB  - Assembly of MHC class I molecules in the ER is regulated by the so-called loading
      complex (LC). This multiprotein complex is of definite importance for class I
      maturation, but its exact organization and order of assembly are not known.
      Evidence implies that the quality of peptides loaded onto class I molecules is
      controlled at multiple stages during MHC class I assembly. We recently found that
      tapasin, an important component of the LC, interacts with COPI-coated vesicles.
      Biochemical studies suggested that the tapa-sin-COPI interaction regulates the
      retrograde transport of immature MHC class I molecules from the Golgi network
      back to the ER. Also other findings now propose that in addition to the peptide
      loading control, the quality control of MHC class I antigen presentation includes
      the restriction of export of suboptimally loaded MHC class I molecules to the
      cell surface. In this review, we use recent studies of tapasin to examine the
      efficiency of TAP, the LC constitution, ER quality control of class I assembly,
      and peptide optimization. The concepts of MHC class I recycling and ER retention
      are also discussed.

PMID- 14718385
TI  - Multiple types of skeletal muscle atrophy involve a common program of changes in
      gene expression.
AB  - Skeletal muscle atrophy is a debilitating response to starvation and many
      systemic diseases including diabetes, cancer, and renal failure. We had proposed
      that a common set of transcriptional adaptations underlie the loss of muscle mass
      in these different states. To test this hypothesis, we used cDNA microarrays to
      compare the changes in content of specific mRNAs in muscles atrophying from
      different causes. We compared muscles from fasted mice, from rats with cancer
      cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal
      nephrectomy, and from pair-fed control rats. Although the content of >90% of
      mRNAs did not change, including those for the myofibrillar apparatus, we found a
      common set of genes (termed atrogins) that were induced or suppressed in muscles
      in these four catabolic states. Among the strongly induced genes were many
      involved in protein degradation, including polyubiquitins, Ub fusion proteins,
      the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the
      20S proteasome and its 19S regulator, and cathepsin L. Many genes required for
      ATP production and late steps in glycolysis were down-regulated, as were many
      transcripts for extracellular matrix proteins. Some genes not previously
      implicated in muscle atrophy were dramatically up-regulated (lipin,
      metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting
      factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1
      BP5). Thus, different types of muscle atrophy share a common transcriptional
      program that is activated in many systemic diseases.

PMID- 14718386
TI  - Molecular cloning and characterization of Mustang, a novel nuclear protein
      expressed during skeletal development and regeneration.
AB  - Bone regeneration occurs as a series of events that requires temporal and spatial
      orchestration of numerous cell types guided by the transcriptional activity of
      thousands of genes, as recently demonstrated by our laboratory. Using the rat
      femoral fracture model, bioinformatics, cloning, expression assays, fusion
      proteins, and transfection, we report on the identification and characterization
      of one such differentially expressed gene, termed Mustang (musculoskeletal
      temporally activated novel gene). Mustang encodes for an 82 amino acid nuclear
      protein with no homology to any known protein family. However, other species
      homologues (mouse, human, cow) were identified within EST (expressed sequence
      tag) databases. Nuclear localization was confirmed using a GFP-Mustang fusion
      protein. Using in situ hybridization, Mustang expression was localized to
      differentiating periosteal osteogenic cells, proliferating chondrocytes, and
      osteoblasts of the fracture callus. Unlike adult tissues, developing embryos
      abundantly express Mustang, especially in mesenchymal condensations of limbs,
      vertebral perichondrium, and mesenchymal cells of the intervertebral discs.
      Although the precise function of Mustang is unknown, its unique pattern of
      expression during bone development and regeneration, absence in adult tissues
      (except skeletal muscle and tendon), and nuclear localization suggest that
      Mustang is involved in the development and regeneration of the mammalian
      musculoskeletal system.

PMID- 14718387
TI  - DSCR1(Adapt78) modulates expression of SOD1.
AB  - DSCR1(Adapt78) is a stress responsive gene that can be induced by multiple
      stresses. We have previously demonstrated that acute DSCR1(Adapt78)
      overexpression can transiently protect cells against oxidative stress and calcium
      mediated stresses, while its chronic overexpression is associated with
      neurofibrillary tangles, Alzheimer disease, and Down's syndrome. It seems that a
      delicate balance of DSCR1(Adapt78) expression is maintained in cells, and this
      gene can have either protective or damaging effects, depending on both its level
      and duration of expression. The mechanisms by which DSCR1(Adapt78) can protect or
      harm cells are poorly understood. Here, we tried to identify pathways and targets
      affected by the DSCR1(Adapt78) gene using regulated expression of DSCR1(Adapt78)
      in PC-12 cells, followed by microarray analysis of mRNAs from these cells. We
      found that DSCR1(Adapt78) expression stimulates SOD1 (intracellular Cu,Zn
      superoxide dismutase) gene expression and increased sod 1 enzyme activity.
      Previous studies have indicated that sod 1 can either protect or damage cells,
      depending on its levels. Our findings suggest that sod 1 may also be involved in
      both the acute protective and the chronic damaging effects of DSCR1(Adapt78)
      expression. These data also have importance for our understanding of Down's
      syndrome, Alzheimer's disease, and other human pathologies.

PMID- 14718388
TI  - Membrane glucocorticoid receptors (mGCR) are expressed in normal human peripheral
      blood mononuclear cells and up-regulated after in vitro stimulation and in
      patients with rheumatoid arthritis.
AB  - Glucocorticoids mediate their therapeutic actions mostly by genomic effects via
      cytosolic receptors, but some effects are too rapid to be mediated by changes at
      the genomic level. The detailed mechanisms of these nongenomic actions are still
      unclear. Membrane-bound glucocorticoid receptors (mGCR) have been suggested to be
      involved, although their physiological existence in humans so far is
      hypothetical. For the first time we demonstrate the existence of mGCR on
      monocytes and B cells obtained from healthy blood donors using high-sensitivity
      immunofluorescent staining. Immunostimulation with lipopolysaccharide increases
      the percentage of mGCR-positive monocytes, which can be prevented by inhibiting
      the secretory pathway. Overexpression of the human glucocorticoid receptor alpha
      alone is not sufficient to enhance mGCR expression. These in vitro findings are
      consistent with our clinical observation that in patients with rheumatoid
      arthritis the frequency of mGCR positive monocytes is increased and positively
      correlated with disease activity. We conclude that mGCR are 1) indeed
      physiologically present in healthy blood donors, but remained unidentified by
      conventional techniques due to their small number per cell and 2) actively up
      regulated and transported through the cell after immunostimulation. These
      receptors may reflect a feedback mechanism of the organism upon immunostimulation
      and/or play a role in pathogenesis.

PMID- 14718389
TI  - Increases in estrogen receptor-alpha concentration in breast cancer cells promote
      serine 118/104/106-independent AF-1 transactivation and growth in the absence of
      estrogen.
AB  - A common phenotype in breast cancer is the expansion of the estrogen receptor
      alpha (ER+) cell population and an inappropriate elevation of ERalpha protein,
      the latter predisposing patients for a poorer prognosis than those with lower
      levels of the receptor. A tetracycline-inducible ERalpha overexpression model was
      developed in the MCF-7 cell line to assess induction of endogenous gene
      activation and growth in response to elevations in ERalpha protein. Heightened
      levels of ERalpha resulted in aberrant promoter occupancy and gene activation in
      the absence of hormone, which was independent of ligand and AF-2 function. This
      increased receptor activity required the amino-terminal A/B domain and was not
      inhibited by tamoxifen, which supports an enhancement of AF-1 function, yet was
      independent of serine-104, 106, and 118 phosphorylation. Ligand-independent
      transcription was accompanied by an increase in growth in the absence of hormonal
      stimulation. The results suggest that elevated levels of ERalpha in breast cancer
      cells can result in activation of receptor transcriptional function in a manner
      distinct from classical mechanisms that involve ligand binding or growth factor
      induced phosphorylation. Further, they describe a potential mechanism whereby
      increases in ERalpha concentration may provide a proliferative advantage by
      augmenting ERalpha function regardless of ligand status.

PMID- 14718390
TI  - Superoxide: a key player in hypertension.
AB  - Superoxide is increased in the vessel wall of spontaneously hypertensive rats
      (SHR) where, if "blocked," potentiates endothelium-dependent vasodilation. The
      purpose of this study was to determine the role of superoxide anion in
      hypertension and its interaction with nitric oxide (NO). For this purpose we used
      a low molecular weight synthetic superoxide dismutase mimetic (M40403), known to
      remove selectively superoxide anion. Baseline mean arterial pressure (MAP) was
      significantly elevated in the SHR compared with its normal counterpart, Wistar
      Kyoto (WKY). M40403 at a dose (2 mg x kg(-1) x h(-1)), which had no effect in the
      WKY, significantly decreased MAP in SHR rats. To determine whether superoxide
      anion increases MAP by inactivating NO, NO synthesis was blocked with N(G) nitro
      arginine methyl ester (L-NAME, 3 mg/kg i.v.), a nonselective nitric oxide
      synthase inhibitor. L-NAME (3 mg/kg, i.v) blocked the anti-hypertensive effect of
      M40403 (2 mg/kg over 30 min). When used at a dose that yielded similar increases
      in MAP, norepinephrine (2.1 microg/kg) failed to alter the anti-hypertensive
      effects of M40403 in the SHR. To investigate whether the anti-hypertensive effect
      of M40403 was associated with an improvement of the alterations in vascular
      reactivity, a separate group of experiments was carried out ex vivo. Endothelium
      dependent vasorelaxation to acetylcholine (10 nM-10 microM), an index of
      endothelial function, was reduced in aortic rings taken from SHR rats when
      compared with WKY rats. In vivo treatment with M40403 caused an improvement of
      the degree of the endothelial dysfunction in SHR rats. Furthermore,
      immunohistochemical analysis for nitrotyrosine (the product formed from the
      interaction of nitric oxide with superoxide) revealed a positive staining in
      aorta from SHR rats. The degree of staining for nitrotyrosine was markedly
      reduced in tissue sections obtained from SHR rats treated with M40403. Our data
      suggest that overt production of superoxide in SHR couples with nitric oxide,
      reducing its function and leading to a loss of blood vessel tone and
      hypertension. Another important effect appears to be at the level of endothelial
      cellular integrity, where by interacting with nitric oxide, superoxide anion
      forms peroxynitrite and subsequent endothelial cell dysfunction. By removing
      superoxide, M40403 restores blood pressure to near-to-normal values.

PMID- 14718391
TI  - Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibers.
AB  - Dystrophin is a cytoskeletal protein found at the inner surface of skeletal and
      cardiac muscle fibers. We hypothesize that deficiency of dystrophin increases
      muscle compliance and causes an aberrant mechanotransduction in muscle fibers. To
      test this hypothesis, we measured the length-tension relationships and determined
      intracellular signaling leading to the activation of mitogen-activated protein
      (MAP) kinases in diaphragm muscle fibers from dystrophin-deficient mdx mice.
      Compared with controls, length-tension curves of the mdx mice were shifted to the
      right. A higher level of activation of extracellular signal-regulated kinase 1/2
      (ERK1/2) but not c-Jun N-terminal kinase-1 or p38 MAP kinase was observed in the
      mdx muscle compared with the normal muscle in response to mechanical stretch.
      Removal of Ca2+ from the medium inhibited stretch-induced ERK1/2 activation only
      in mdx muscle fibers but not in the normal fibers. Conversely, pretreatment with
      TMB-8 (an antagonist of intracellular Ca2+ blocked the mechanical stretch-induced
      ERK1/2 activation in normal but not in mdx muscle fibers. Pretreatment of muscle
      with nifedipine (L-type calcium channel antagonist) marginally decreased the
      activation of ERK1/2 in normal or mdx muscle whereas pretreatment with gadolinium
      (III) chloride (an inhibitor of stretch-activated channels) only blocked the
      activation of ERK1/2 in mdx muscle, with no significant effect on normal muscle.
      A higher basal level of activation of activator protein-1 (AP-1) transcription
      factor was observed in dystrophin-deficient diaphragm, which was further
      augmented by mechanical stretch. Mechanical stretch-induced activation of AP-1
      was decreased by pretreatment of muscle fibers with PD98059 (ERK1/2 inhibitor)
      and removal of Ca2+ ions from incubation medium. Our results show that dystrophin
      is a load-bearing element and its deficiency leads to loss of muscle stiffness
      and aberrant mechanotransduction in skeletal muscle fibers.

PMID- 14718392
TI  - A functionally atypical amidating enzyme from the human parasite Schistosoma
      mansoni.
AB  - Many neuropeptide transmitters require the presence of a carboxy-terminal alpha
      amide group for biological activity. Amidation requires conversion of a glycine
      extended peptide intermediate into a C-terminally amidated product. This post
      translational modification depends on the sequential action of two enzymes
      (peptidylglycine alpha-hydroxylating monooxygenase or PHM, and peptidyl-alpha
      hydroxyglycine alpha-amidating lyase or PAL) that in most eukaryotes are
      expressed as separate domains of a single protein (peptidylglycine alpha
      amidating monooxygenase or PAM). We identified a cDNA encoding PHM in the human
      parasite Schistosoma mansoni. Transient expression of schistosome PHM (smPHM)
      revealed functional properties that are different from other PHM proteins; smPHM
      displays a lower pH-optimum and, when expressed in mammalian cells, is heavily N
      glycosylated. In adult worms, PHM is found in the trans-Golgi network and
      secretory vesicles of both central and peripheral nerves. The widespread
      occurrence of PHM in the nervous system confirms the important role of amidated
      neuropeptides in these parasitic flatworms. The differences between schistosome
      and mammalian PHM suggest that it could be a target for new chemotherapeutics.

PMID- 14718393
TI  - Methodology in diagnostic laboratory test research in clinical chemistry and
      clinical chemistry and laboratory medicine.
AB  - BACKGROUND: The application of epidemiologic principles to clinical diagnosis has
      been less developed than in other clinical areas. Knowledge of the main flaws
      affecting diagnostic laboratory test research is the first step for improving its
      quality. We assessed the methodologic aspects of articles on laboratory tests.
      METHODS: We included articles that estimated indexes of diagnostic accuracy
      (sensitivity and specificity) and were published in Clinical Chemistry or
      Clinical Chemistry and Laboratory Medicine in 1996, 2001, and 2002. Clinical
      Chemistry has paid special attention to this field of research since 1996 by
      publishing recommendations, checklists, and reviews. Articles were identified
      through electronic searches in Medline. The strategy combined the Mesh term
      "sensitivity and specificity" (exploded) with the text words "specificity",
      "false negative", and "accuracy". We examined adherence to seven methodologic
      criteria used in the study by Reid et al. (JAMA1995;274:645-51) of papers
      published in general medical journals. Three observers evaluated each article
      independently. RESULTS: Seventy-nine articles fulfilled the inclusion criteria.
      The percentage of studies that satisfied each criterion improved from 1996 to
      2002. Substantial improvement was observed in reporting of the statistical
      uncertainty of indices of diagnostic accuracy, in criteria based on clinical
      information from the study population (spectrum composition), and in avoidance of
      workup bias. Analytical reproducibility was reported frequently (68%), whereas
      information about indeterminate results was rarely provided. The mean number of
      methodologic criteria satisfied showed a statistically significant increase over
      the 3 years in Clinical Chemistry but not in Clinical Chemistry and Laboratory
      Medicine. CONCLUSIONS: The methodologic quality of the articles on diagnostic
      test research published in Clinical Chemistry and Clinical Chemistry and
      Laboratory Medicine is comparable to the quality observed in the best general
      medical journals. The methodologic aspects that most need improvement are those
      linked to the clinical information of the populations studied. Editorial actions
      aimed to increase the quality of reporting of diagnostic studies could have a
      relevant positive effect, as shown by the improvement observed in Clinical
      Chemistry.

PMID- 14718394
TI  - Interlaboratory comparison of fetal male DNA detection from common maternal
      plasma samples by real-time PCR.
AB  - BACKGROUND: Analysis of fetal DNA from maternal plasma by PCR offers great
      potential for noninvasive prenatal genetic diagnosis. To further evaluate this
      potential, we developed and validated a standard protocol to determine whether
      fetal DNA sequences could be reproducibly amplified and measured across multiple
      laboratories in a common set of specimens. METHODS: Each of five participating
      centers in a National Institute of Child Health and Human Development consortium
      collected 20 mL of peripheral blood from 20 pregnant women between 10 and 20
      weeks of gestation. The plasma fraction was separated according to a common
      protocol, divided, and frozen in five aliquots. One aliquot was shipped to each
      participating laboratory, where DNA was extracted according to a standard
      protocol. All plasma samples (n = 100) were then analyzed blindly for the
      presence and quantity of total DNA (GAPDH) and male fetal DNA (SRY) by real-time
      PCR. Genomic DNA was isolated from female and male cells at one center,
      quantified, and shipped to the others to serve as calibrators for GAPDH and SRY,
      respectively. RESULTS: The amplification of known quantities of DNA was
      consistent among all centers. The mean quantity of male DNA amplified from
      maternal plasma when the fetus was male ranged from 51 to 228 genome equivalents
      (GE)/mL. Qualitative concordance was found overall among centers. The sensitivity
      of the assay for detection of male DNA when the fetus was male varied from 31% to
      97% among centers. Specificity was more consistent (93-100%) with only four false
      positive results obtained across the entire study. CONCLUSIONS: All centers were
      able to consistently amplify frozen and shipped DNA. The PCR procedure used here
      is reliable and reproducible. Centers that extracted and amplified more DNA per
      milliliter of maternal plasma had superior sensitivities of Y chromosome sequence
      detection. The specificity of the assay was more consistent among centers. A
      robust and thoroughly optimized protocol for the extraction of DNA from maternal
      plasma is needed to make testing of fetal DNA in maternal plasma a clinically
      relevant analytical tool.

PMID- 14718395
TI  - Rapid detection of K-ras mutations in bile by peptide nucleic acid-mediated PCR
      clamping and melting curve analysis: comparison with restriction fragment length
      polymorphism analysis.
AB  - BACKGROUND: Current methods for detection of K-ras gene mutations are time
      consuming. We aimed to develop a one-step PCR technique using fluorescent
      hybridization probes and competing peptide nucleic acid oligomers to detect K-ras
      mutations in bile and to compare the efficacy with restriction fragment length
      polymorphism (RFLP) analysis. METHODS: Bile samples were obtained from 116
      patients with biliary obstruction, including gallstones (n = 64), benign biliary
      strictures (n = 6), pancreatic cancer (n = 20), and cholangiocarcinoma (n = 26).
      The DNA was extracted and subjected to K-ras mutation analysis by real-time PCR
      and RFLP analysis. Mutations were confirmed by direct sequencing. The sensitivity
      and specificity were calculated according to the clinical results. RESULTS: The
      analysis time for real-time PCR was <1 h, whereas RFLP analysis took more than 2
      days. With the sensor probe designed for the GAT (G12D) mutant in codon 12 of the
      K-ras gene, the real-time PCR method also detected the GTT (G12V) mutant. In
      contrast, a specific sensor probe for the TGT (G12C) mutant detected GAT (G12D),
      AGT (G12S), and GTT (G12V) mutants in addition to the TGT mutant. The real-time
      PCR assay allowed the detection of mutation in a 3000-fold excess of wild-type
      bile DNA. In bile, K-ras codon 12 mutations were detected in 16 of 46 malignant
      cases by real-time PCR with the TGT probe and 15 by RFLP analysis. All benign
      cases were wild type. CONCLUSION: Real-time PCR with a cysteine-specific (TGT)
      sensor probe can rapidly detect K-ras gene mutations in bile and diagnose
      malignant biliary obstruction with high specificity.

PMID- 14718396
TI  - Potential clinical utility of a new IRMA for parathyroid hormone in
      postmenopausal patients with primary hyperparathyroidism.
AB  - BACKGROUND: A new commercially available (so-called second-generation) IRMA for
      parathyroid hormone (PTH) separately detects intact PTH and its N-truncated
      fragments; however, no studies have compared the first- and second-generation
      IRMAs for PTH in patients with primary hyperparathyroidism (PHPT) to assess their
      respective diagnostic accuracies. METHODS: We concomitantly investigated 39
      postmenopausal patients with PHPT and a control group of 70 healthy
      postmenopausal women matched for age, renal function, and vitamin D status. In
      all individuals, PTH was measured with a classic IRMA (PTH-S; DiaSorin Inc.),
      which uses antibodies directed against epitopes 1-34 and 39-84, and a new method
      (Scantibodies Laboratory. Inc.), which uses antibodies against epitopes 1-4 and
      39-84 (PTH-W) and epitopes 7-34 and 39-84 (PTH-T). We also assayed serum PTH in
      10 PHPT patients every 24 h for 5 days after successful surgery. RESULTS: The
      different assays gave serum PTH values that were >2 SD higher than values for the
      control population in 59% (PTH-S), 77% (PTH-W), and 82% (PTH-T) of patients with
      PHPT. However, ROC curve analysis showed no significant differences among the
      three PTH assays, demonstrating overlapping diagnostic sensitivities. In PHPT
      patients, the correlation among the assays was highly significant (r = 0.91-0.92;
      P <0.001). The ratio PTH-W:PTH-T x 100 showed a gaussian distribution in both
      PHPT patients and controls, whose mean (SD) values [63.4 (13.3)% vs 64.5 (9.5)%,
      respectively] did not differ significantly. After parathyroidectomy, the mean
      percentages of variation in PTH detected with all of the assays were quite
      similar. CONCLUSIONS: The distribution of the PTH-W:PTH-T ratio in patients and
      controls suggests that PHPT does not markedly influence the rate at which
      biologically inactive fragments are generated by central or peripheral cleavage
      of PTH. The similar postoperative curves seem to contradict the hypothesized
      effect of acute hypocalcemia in modulating the central secretion of hormonal
      fragments. Our results indicate that the three investigated assays have similar
      diagnostic sensitivities in PHPT.

PMID- 14718397
TI  - Pyrosequencing technology as a method for the diagnosis of multiple endocrine
      neoplasia type 2.
AB  - BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a cancer syndrome with
      well-characterized causative mutations. Missense mutations in approximately 15
      codons of the RET gene have been linked to disease phenotypes in the vast
      majority of cases. These missense mutations range from very simple single
      nucleotide base changes to more numerous changes at a given codon; they therefore
      are often tested for by more than one DNA-based diagnostic method. We developed
      and evaluated a Pyrosequencing technology-based approach for MEN2 mutation
      testing that allows both simple and complex mutations to be analyzed on one
      platform. METHODS: Archived DNA from peripheral blood of patients referred to the
      Mayo Clinic Molecular Genetics laboratory for MEN2 testing was selected. One to
      all of codons 609, 611, 618, 620, 630, 634, 768, 804, and 918 were analyzed by
      Pyrosequencing technology to match the original analysis of each patient.
      Template PCRs were set up using an automated liquid handler; the subsequent post
      PCR preparation step was performed manually, and the sequencing was performed by
      a PSQ 96 instrument. Samples were tested in batch sizes expected to occur
      routinely. RESULTS: We analyzed samples from 217 patients who previously tested
      negative for MEN2 and 230 patients who previously tested positive, for a total of
      1449 sequencing reactions. One discrepant result was found (100% concordant for
      negatives and 99.6% concordant for positives). A total of 37 unique mutations or
      alterations of unknown significance were analyzed. CONCLUSION: Pyrosequencing
      technology offers an accurate, nonisotopic, simple, and rapid method for the
      analysis of DNA from patients suspected of having MEN2.

PMID- 14718398
TI  - Characterization of amplifiable, circulating RNA in plasma and its potential as a
      tool for cancer diagnostics.
AB  - BACKGROUND: Several recent reports have described the detection of circulating,
      cancer-related RNA molecules in serum or plasma from cancer patients, but little
      is known about the biology of this extracellular RNA. We aimed to determine how
      RNA is protected against degradation in serum, to optimize RNA isolation from
      large volumes of serum, and to test our optimized assays for serum-based cancer
      detection. METHODS: We used quantitative reverse transcription-PCR (QRT-PCR)
      analysis to investigate the isolation and biology of extracellular plasma RNA. We
      then examined the presence of amplifiable RNA transcripts in plasma and serum
      from controls and from patients with esophageal cancer and malignant melanoma.
      RESULTS: We found that extracellular RNA in plasma is highly degraded and can be
      isolated most efficiently by guanidinium-phenol extraction followed by
      precipitation. Extracellular RNA is stable in serum for up to 3 h but is
      destroyed immediately by addition of detergents. Extracellular RNA can be
      captured on 0.2 microm filters, allowing concentration of RNA from several
      milliliters of plasma. When we concentrated RNA from up to 4 mL of serum,
      detection of cancer-related transcripts in serum from cancer patients and
      controls was infrequent and inconsistent. CONCLUSIONS: Extracellular RNA is most
      likely protected within protein or lipid vesicles, possibly apoptotic bodies,
      which can be disrupted by detergents. Despite optimizing many aspects of plasma
      RNA detection, we were unable to reproducibly detect cancer-related transcripts.
      Our data suggest that measurement of circulating RNA may not be a good approach
      to early cancer diagnosis.

PMID- 14718399
TI  - Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase.
AB  - BACKGROUND: Recent evidence has suggested that reactive oxygen species are
      important signaling molecules in vascular cells and play a pivotal role in the
      development of vascular diseases. The activity of NAD(P)H oxidase has been
      identified as the major source of reactive oxygen species in vascular endothelial
      cells. However, the precise molecular structure and the mechanism of activation
      of the oxidase have remained poorly understood. METHODS AND RESULTS: Here, we
      investigated the molecular identities and the superoxide-producing activity of
      endothelial NAD(P)H oxidase. We found that Nox4, a homologue of gp91phox/Nox2,
      was abundantly expressed in endothelial cells. The expression of Nox4 in
      endothelial cells markedly exceeded that of other Nox proteins, including
      gp91phox/Nox2, and was affected by cell growth. Using electron spin resonance and
      chemiluminescence, we measured the superoxide production and found that the
      endothelial membranes had an NAD(P)H-dependent superoxide-producing activity
      comparable to that of the neutrophil membranes, whereas the activity was not
      enhanced by the 2 recombinant proteins p47phox and p67phox, in contrast to that
      of the neutrophil membranes. Downregulation of Nox4 by an antisense
      oligonucleotide reduced superoxide production in endothelial cells in vivo and in
      vitro. CONCLUSIONS: These findings suggest that Nox4 may function as the major
      catalytic component of an endothelial NAD(P)H oxidase.

PMID- 14718400
TI  - 17beta-estradiol antagonizes cardiomyocyte hypertrophy by autocrine/paracrine
      stimulation of a guanylyl cyclase A receptor-cyclic guanosine monophosphate
      dependent protein kinase pathway.
AB  - BACKGROUND: Significant gender-related differences exist in the development of
      left ventricular hypertrophy (LVH). In addition, administration of 17beta
      estradiol (E2) to ovariectomized female mice attenuates the development of LVH,
      demonstrating an antagonistic role for E2 in this process, although no molecular
      mechanism has been proposed for this phenomenon. METHODS AND RESULTS: E2
      attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal
      cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF)
      expression as assessed by Northern blot, immunocytochemical analyses, and
      transient transfection assays using ANF promoter deletion fragments. Both the
      antihypertrophic effects and ANF induction could be blocked by the estrogen
      receptor antagonist ICI 182,780, which demonstrates a genomic, estrogen receptor
      dependent pathway. To mimic E2-induced autocrine/paracrine effects through
      stimulation of the guanylyl cyclase A receptor (ANF receptor), cardiomyocytes
      were stimulated with phenylephrine or endothelin-1 in the presence of exogenous
      ANF or 8-bromo-cyclic guanosine monophosphate (cGMP), both of which attenuated
      agonist-induced hypertrophy. Both estrogen and ANF increased cGMP activity. The
      antihypertrophic effect of ANF could be reduced with extracellular ANF antibodies
      in a dose-dependent manner. cGMP-dependent protein kinase mediates the
      antihypertrophic effects of E2, so cardiomyocytes were agonist stimulated in the
      presence of the cGMP-dependent protein kinase blocker KT-5823. KT-5823 not only
      reversed the antihypertrophic properties of E2, ANF, or 8-bromo-cGMP, but also
      evoked potentiation of hypertrophy. CONCLUSIONS: E2-mediated induction of ANF in
      cardiac hypertrophy contributes to its antagonistic effects in LVH.

PMID- 14718401
TI  - Conditional cardiac overexpression of endothelin-1 induces inflammation and
      dilated cardiomyopathy in mice.
AB  - BACKGROUND: Myocardial expression of endothelin-1 (ET-1) and its receptors ET(A)
      and ET(B) is increased in heart failure. However, the role of ET-1 and its
      signaling pathways in the pathogenesis of myocardial diseases is unclear. METHODS
      AND RESULTS: Human ET-1 cDNA was placed downstream of a promoter responsive to a
      doxycycline (DOX)-regulated transcriptional activator (tTA). This line (ET+) was
      bred with one harboring cardiac myocyte-restricted expression of tTA (alphaMHC
      tTA). Myocardial ET-1 peptide levels were significantly increased in binary
      transgenic (BT, ET+/tTA+) compared with nonbinary transgenic (NBT, ET+/tTA-; ET
      /tTA+; ET-/tTA-) or DOX-treated BT littermates (40.1+/-4.7 versus 2.6+/-1.2
      fmol/mL, P<0.003). BT mice demonstrated progressive mortality between 5 and 11
      weeks after DOX withdrawal, associated with left ventricular dilatation and
      contractile dysfunction (peak +dP/dT, 4673+/-468 versus 5585+/-658 mm Hg/s,
      P<0.05). An interstitial inflammatory infiltrate, including macrophages and T
      lymphocytes, was evident in the myocardium of BT mice, associated with sequential
      increases in nuclear factor-kappaB translocation and expression of tumor necrosis
      factor-alpha, interferon-gamma, interleukin-1 and interleukin-6. Significant
      prolongation of survival was observed with the combined ET(A)/ET(B) antagonist
      LU420627 (n=8, P<0.05) in BT mice but not the ET(A)-selective antagonist LU135252
      (n=5, P=0.9), consistent with an important role for ET(B) in this model.
      CONCLUSIONS: These are the first data to demonstrate that cardiac overexpression
      of ET-1 is sufficient to cause increased expression of inflammatory cytokines and
      an inflammatory cardiomyopathy leading to heart failure and death.

PMID- 14718402
TI  - Role of magnetic resonance angiography in the diagnosis of major aortopulmonary
      collateral arteries and partial anomalous pulmonary venous drainage.
AB  - BACKGROUND: Accurate diagnosis of major aortopulmonary collaterals (MAPCAs) and
      partial anomalous pulmonary venous drainage (PAPVD) in adult patients with
      congenital heart disease is important but problematic. Three-dimensional contrast
      enhanced magnetic resonance angiography (MRA) provides a minimally invasive
      technique to allow detailed studies in a single breath-hold. METHODS AND RESULTS:
      We assessed the role of contrast-enhanced 3D MRA in 29 consecutive adult patients
      with a diagnosis of MAPCAs (n=16) or PAPVD (n=13) made by echocardiogram, cardiac
      catheterization, or surgical inspection. MRA was performed with a 3D spoiled
      gradient-echo technique with intravenous gadolinium-DTPA (0.2 mmol/kg). In both
      types of pathology, there was excellent correlation between MRA and the cardiac
      catheterization, echocardiogram, or surgical inspection. Additional information
      was gained for patients with MAPCAs on confluence and size of pulmonary arteries
      (n=13 had central arteries), pulmonary artery stenosis (n=3), aneurysmal
      dilatation of pulmonary artery (n=1), and additional anomalous vascular
      abnormality (n=3). Shunt assessment, where present (9 of 16), showed patency in
      all cases (100%). For adults with PAPVD, further information was obtained on
      drainage origin (n=11). There were no complications. CONCLUSIONS: Contrast
      enhanced 3D MRA provides a fast, noninvasive, radiation-free method of accurate
      and comprehensive diagnosis of MAPCAs and PAPVD in adult patients.

PMID- 14718403
TI  - Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in
      patients with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Adrenomedullin (AM) is a potent pulmonary vasodilator peptide.
      However, whether intratracheal delivery of aerosolized AM has beneficial effects
      in patients with idiopathic pulmonary arterial hypertension remains unknown.
      Accordingly, we investigated the effects of AM inhalation on pulmonary
      hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial
      hypertension. METHODS AND RESULTS: Acute hemodynamic responses to inhalation of
      aerosolized AM (10 microg/kg body wt) were examined in 11 patients with
      idiopathic pulmonary arterial hypertension during cardiac catheterization.
      Cardiopulmonary exercise testing was performed immediately after inhalation of
      aerosolized AM or placebo. The work rate was increased by 15 W/min until the
      symptom-limited maximum, with breath-by-breath gas analysis. Inhalation of AM
      produced a 13% decrease in mean pulmonary arterial pressure (54+/-3 to 47+/-3 mm
      Hg, P<0.05) and a 22% decrease in pulmonary vascular resistance (12.6+/-1.5 to
      9.8+/-1.3 Wood units, P<0.05). However, neither systemic arterial pressure nor
      heart rate was altered. Inhalation of AM significantly increased peak oxygen
      consumption during exercise (peak o(2), 14.6+/-0.6 to 15.7+/-0.6 mL. kg(-1). min(
      1), P<0.05) and the ratio of change in oxygen uptake to that in work rate
      (Deltao(2)/DeltaW ratio, 6.3+/-0.4 to 7.0+/-0.5 mL. min(-1). W(-1), P<0.05).
      These parameters remained unchanged during placebo inhalation. CONCLUSIONS:
      Inhalation of AM may have beneficial effects on pulmonary hemodynamics and
      exercise capacity in patients with idiopathic pulmonary arterial hypertension.

PMID- 14718404
TI  - Prenatal exposure to carbon monoxide affects postnatal cellular
      electrophysiological maturation of the rat heart: a potential substrate for
      arrhythmogenesis in infancy.
AB  - BACKGROUND: Maternal smoking is an independent risk factor for sudden infant
      death syndrome (SIDS). Carbon monoxide (CO) is a major component of smoke. No
      information is available about the effect of CO and/or smoking on postnatal
      maturation of the heart. The aim of this study was to investigate the effect of
      prenatal exposure to CO on cellular electrophysiological maturation in male
      Wistar rats. METHODS AND RESULTS: The patch-clamp technique was used to measure
      action potential (AP) and ionic currents (I(to) and I(Ca,L)) from rat ventricular
      myocytes. During growth, AP duration measured at -20 and -50 mV (APD(-)(20) and
      APD(-)(50)) decreased progressively in both groups; the process was significantly
      delayed in rats exposed prenatally to 150 ppm CO: At 4 weeks, APD(-)(20) and APD(
      )(50) were 89.5+/-18.2 and 147.7+/-24.5 ms in CO (n=13) and 35.6+/-4.5 and 77.8+/
      8.3 ms in control rats (Ctr; n=14; P<0.01 and P<0.05, respectively) and
      normalized at 8 weeks. At 4 weeks, the density of I(Ca,L) was significantly
      higher (21.3+/-1.6 pA/pF, n=17, versus 15.9+/-1.6 pA/pF, n=22; P<0.05) and the
      density of I(to) significantly lower (9.6+/-1.5, n=22, versus 15.2+/-2.2 pA/pF,
      n=19; P<0.01) in CO than in Ctr and normalized thereafter. CONCLUSIONS: Prenatal
      CO exposure affects the physiological shortening of APD in neonatal rats. We
      speculate that a prolonged myocyte repolarization induced by prenatal exposure to
      smoke may establish a period of vulnerability for life-threatening arrhythmias in
      infancy.

PMID- 14718405
TI  - Dissociation between ionic remodeling and ability to sustain atrial fibrillation
      during recovery from experimental congestive heart failure.
AB  - BACKGROUND: Congestive heart failure (CHF) downregulates atrial transient outward
      (I(to)), slow delayed rectifier (I(Ks)), and L-type Ca(2+) (I(Ca,L)) currents and
      upregulates Na(+)-Ca(2+) exchange current (I(NCX)) (ionic remodeling) and causes
      atrial fibrosis (structural remodeling). The relative importance of ionic versus
      structural remodeling in CHF-related atrial fibrillation (AF) is controversial.
      METHODS AND RESULTS: We measured hemodynamic and echocardiographic parameters,
      mean duration of burst pacing-induced AF (DAF), and atrial-myocyte ionic currents
      in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs
      allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left
      ventricular ejection fraction averaged 58.6+/-1.2% (control), 36.2+/-2.3% (CHF,
      P<0.01), and 57.9+/-1.6% (REC), indicating full hemodynamic recovery. Similarly,
      left atrial pressures were 2.2+/-0.3 (control), 13.1+/-1.5 (CHF), and 2.4+/-0.4
      (REC) mm Hg. CHF reduced I(to) density by approximately 65% (P<0.01), decreased
      I(Ca,L) density by approximately 50% (P<0.01), and diminished I(Ks) density by
      approximately 40% (P<0.01) while increasing I(NCX) density by approximately 110%
      (P<0.05). In REC, all ionic current densities returned to control values. DAF
      increased in CHF (1132+/-207 versus 14.3+/-8.8 seconds, control) and remained
      increased with REC (1014+/-252 seconds). Atrial fibrous tissue content also
      increased in CHF (2.1+/-0.2% for control versus 10.2+/-0.7% for CHF, P<0.01),
      with no recovery observed in REC (9.4+/-0.8%, P<0.01 versus control, P=NS versus
      CHF). CONCLUSIONS: With reversal of CHF, there is complete recovery of ionic
      remodeling, but the prolonged-AF substrate and structural remodeling remain. This
      suggests that structural, not ionic, remodeling is the primary contributor to AF
      maintenance in experimental CHF.

PMID- 14718406
TI  - Clinical features of acute coronary syndromes in patients with human
      immunodeficiency virus infection.
AB  - BACKGROUND: Patients with HIV infection exhibit increased rates of coronary
      events; however, the clinical features of acute coronary syndromes (ACS) in HIV
      infected patients have not been well defined. METHODS AND RESULTS: Between 1993
      and 2003, 68 HIV-infected patients were hospitalized with ACS. We compared the
      clinical features and outcome of these patients with those of 68 randomly
      selected control patients with ACS without HIV. HIV patients were on average more
      than a decade younger than controls and more likely to be male and current
      smokers and to have low HDL cholesterol. They were less likely than controls to
      have diabetes or hyperlipidemia, and their TIMI (Thrombolysis In Myocardial
      Infarction) risk scores on admission were significantly lower. At coronary
      angiography, the number of vessels with >50% stenosis was 1.3+/-1.0 in HIV
      patients and 1.9+/-1.2 in controls (P=0.007). Restenosis developed in 15 of 29
      HIV patients who underwent percutaneous coronary intervention compared with 3 of
      21 controls (52% versus 14%, P=0.006). CONCLUSIONS: HIV patients with ACS are
      younger and more likely to be males and current smokers and to have low HDL
      cholesterol levels compared with other ACS patients. Their TIMI risk scores are
      lower, and they are more likely to have single-vessel disease; however, their
      restenosis rates after percutaneous coronary intervention are unexpectedly high.

PMID- 14718408
TI  - Exercise for fun and profit: joint statement on exercise by the American Thoracic
      Society and the American College of Chest Physicians.

PMID- 14718409
TI  - The answer is fifteen percent: what is the question?

PMID- 14718410
TI  - To B or not to B?: it still is the question.

PMID- 14718411
TI  - Tracheostomy for respiratory failure: we need more answers.

PMID- 14718412
TI  - Long-acting bronchodilators are the first-choice option for the treatment of
      stable COPD.

PMID- 14718413
TI  - Exhaled nitric oxide in pathophysiologic states: the substance behind the gas.

PMID- 14718414
TI  - A proper balance.

PMID- 14718415
TI  - Smoking patterns in African Americans and whites with advanced COPD.
AB  - BACKGROUND: The prevalence and mortality associated with COPD increases with age,
      with higher rates observed in whites than African Americans. Causes and
      explanations for smoking-related racial differences on the respiratory system
      have not been determined. OBJECTIVE: To investigate racial differences in smoking
      patterns and lung function in patients with advanced COPD. DESIGN: Retrospective
      record review of patients with advanced COPD. SETTING: Outpatient pulmonary
      clinic in a tertiary-care urban hospital. PATIENTS: One hundred sixty patients
      with advanced COPD (80 African Americans and 80 whites) referred for either lung
      volume reduction surgery or transplantation evaluation. DATA COLLECTION:
      Demographics, smoking profile, pulmonary function testing, arterial blood gases,
      and exercise stress tests were compared between African-American and white
      patients. RESULTS: Despite comparable pulmonary function, African Americans were
      younger at presentation and had lower overall pack-years of smoking than whites
      (58 +/- 10 years vs 62 +/- 8 years, and 44 +/- 23 pack-years vs 66 +/- 31 pack
      years, respectively; p < 0.05 [mean +/- SD]). Additionally, African Americans
      started smoking later in life than whites (18 +/- 5 years vs 16 +/- 4 years).
      Similarly, women presented at a younger age and smoked less compared to men (58
      +/- 9 years vs 62 +/- 9 years, and 49 +/- 28 pack-years vs 61 +/- 29 pack-years,
      respectively; p < 0.05), without showing any difference in lung function or
      exercise performance. CONCLUSION: Among susceptible patients with advanced COPD,
      African Americans and women seem more prone to the effects of tobacco smoke than
      their counterparts.

PMID- 14718416
TI  - Markers of inflammation in exhaled breath condensate of young healthy smokers.
AB  - INTRODUCTION: Although a strong correlation exists between long-term cigarette
      smoking, pulmonary inflammation, and COPD, efforts to identify populations at
      risk of acquiring COPD have so far been unsuccessful. To this end, noninvasive
      detection and monitoring of biomarkers of pulmonary inflammation in young healthy
      smokers may assist in this task. STUDY OBJECTIVES: The purpose of this study was
      to determine the concentrations of total protein, nitrites, interleukin (IL)
      1beta, and tumor necrosis factor (TNF)-alpha, and neutrophil chemotactic activity
      in exhaled breath condensate (EBC) collected from healthy college student smokers
      and nonsmokers. DESIGN: EBC was collected from 20 volunteers (9 nonsmokers and 11
      smokers) during tidal breathing for 20 min. EBC was also collected from smokers
      30 min after smoking one filtered cigarette. The concentrations of total protein,
      nitrite, IL-1beta, and TNF-alpha in EBC was determined by enzyme-linked
      immunosorbent assay. Neutrophil chemotactic activity in EBC was determined in
      vitro using the blind-well technique. RESULTS: The concentrations of total
      protein and nitrite, and neutrophil chemotactic activity were significantly
      higher in EBC of smokers in comparison to nonsmokers (p < 0.05). The
      concentrations of total protein and nitrite in the condensate of smokers did not
      change significantly after smoking one cigarette. The concentrations of IL-1beta
      and TNF-alpha in EBC were similar in nonsmokers and smokers. CONCLUSIONS:
      Concentrations of certain inflammatory mediators and neutrophil chemotactic
      activity are increased in EBC of young healthy smokers. Collection and analysis
      of EBC may assist in early detection of cigarette smoke-induced pulmonary
      inflammation and identifying populations at risk for acquiring COPD.

PMID- 14718417
TI  - Smoking and lung cancer survival: the role of comorbidity and treatment.
AB  - STUDY OBJECTIVE: Numerous studies indicate that smoking is associated with poorer
      outcomes in patients with cancer. The aim of this study was to determine whether
      smoking independently predicts survival in patients with lung cancer or whether
      an existent effect is mediated through comorbidity and/or treatment. DESIGN AND
      SETTING: Cox proportional hazards analysis was used to study a cohort of 1,155
      patients with lung cancer diagnosed at the Henry Ford Health System between 1995
      and 1998, inclusive. RESULTS: Adjusted for the baseline covariates, age, gender,
      illicit drug use, adverse symptoms, histology, and stage, the hazard ratio (HR)
      for smoking (current vs former/never) was 1.37 (95% confidence interval [CI],
      1.18 to 1.59; p < 0.001). Adjusted for the baseline covariates and for 18
      deleterious comorbidities, the HR for smoking was 1.38 (95% CI, 1.18 to 1.60; p <
      0.001), indicating that the hazardous effect of smoking was not mediated through
      comorbidity. Current smoking was inversely associated with treatment (any surgery
      and/or chemotherapy and/or radiation therapy vs none) [odds ratio, 0.73; 95% CI,
      0.55 to 0.98 (p = 0.03)]. Adjusted for baseline covariates, comorbidities and
      treatment, the HR for current smoker vs former/never was 1.26 (95% CI, 1.08 to
      1.47; p = 0.003), a decline of 30.7% explained by treatment (HR for any treatment
      vs none, 0.40; 95% CI, 0.33 to 0.48; p < 0.001). CONCLUSIONS: Current smoking at
      diagnosis is an important independent predictor of shortened lung cancer
      survival. That this effect was not explained by sociodemographic/exposure
      factors, adverse symptoms, histology, stage, comorbidity, and treatment suggests
      that it may be mediated through direct biological effects.

PMID- 14718418
TI  - Resection of the right middle lobe and lingula in children for middle
      lobe/lingula syndrome.
AB  - STUDY OBJECTIVE: To review our experience with specific characteristics,
      indications, and results of pulmonary resection in children with middle
      lobe/lingula syndrome. DESIGN: Retrospective cohort study. SETTING: Thoracic
      Surgery Department, Chest Diseases Hospital, Kuwait. PATIENTS AND INTERVENTION:
      Thirteen children with middle lobe, lingula, or both syndromes were treated with
      pulmonary resection from January 1995 to December 1999. RESULTS: The mean age was
      7.5 years (range, 5 to 10 years). Eight patients were girls, and five were boys.
      All patients underwent high-resolution CT and bronchoscopy. Bronchiectasis and
      atelectasis of right middle lobe, lingula, or both was noted in nine patients.
      Bronchial stenosis and inflammation of the bronchus was found endoscopically in
      four patients. The indications for surgery were recurrent respiratory tract
      infection with persistent atelectasis and bronchiectasis in nine patients, and
      recurrent respiratory tract infection with bronchiectasis in four patients. A
      right middle lobectomy was done on seven patients and a lingulectomy on four
      patients. Two patients underwent staged thoracotomies (right middle lobectomy and
      lingulectomy). There were no operative deaths. Only two patients had
      postoperative complications: atelectasis (n = 1), and pneumothorax (n = 1). Mean
      follow-up was 3.5 years (range, 3 to 5 years) for all patients. Nine patients
      were asymptomatic, and four patients had improved. CONCLUSION: Right middle lobe
      or lingula syndrome with the presence of bronchiectasis, bronchial stenosis, or
      failure of lung to re-expand are indications for early pulmonary resection.

PMID- 14718419
TI  - Effect of three wound dressings on infection, healing comfort, and cost in
      patients with sternotomy wounds: a randomized trial.
AB  - STUDY OBJECTIVE: To compare three dressing types in terms of their ability to
      protect against infection and promote healing, patient comfort, and cost
      effectiveness. DESIGN: Prospective, randomized controlled trial. SETTING: Major
      metropolitan, academically affiliated, tertiary referral center. PATIENTS: Seven
      hundred thirty-seven patients were randomized to receive a dry absorbent dressing
      (n = 243) [Primapore; Smith & Nephew; Sydney, NSW, Australia], a hydrocolloid
      dressing (n = 267) [Duoderm Thin ConvaTec; Mulgrave, VIC, Australia], or a
      hydroactive dressing (n = 227) [Opsite; Smith & Nephew] in the operating theater
      on skin closure. RESULTS: There was no difference in the rate of wound infection
      or wound healing between treatment groups. The Primapore dressing was the most
      comfortable and cost-effective dressing option for the sternotomy wound. Duoderm
      Thin dressings were associated with increased wound exudate (p < 0.001), poor
      dressing integrity (p < 0.001), more frequent dressing changes (p < 0.001), more
      discomfort with removal (p < 0.05), and increased cost (p < 0.001). CONCLUSIONS:
      In the context of no additional benefit for the prevention of wound infection or
      the rate of wound healing for any of the three dressing products examined, dry
      absorbent dressings are the most comfortable and cost-effective products for
      sternotomy wounds following cardiac surgery.

PMID- 14718420
TI  - Effects of additional minocycline pleurodesis after thoracoscopic procedures for
      primary spontaneous pneumothorax.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of additional minocycline
      pleurodesis after thoracoscopic treatment of primary spontaneous pneumothorax.
      DESIGN: Retrospective comparative study with a historical control. SETTING:
      Thoracic surgical division of a university-affiliated tertiary medical center.
      PATIENTS AND METHODS: Between April 1994 and April 2001, 313 consecutive patients
      (minocycline group) with primary spontaneous pneumothorax were treated by video
      assisted thoracoscopic surgery. The procedures included resection of the blebs
      and mechanical pleurodesis by scrubbing the parietal pleura. After operation,
      minocycline hydrochloride, 7 mg/kg, was instilled into the pleural space through
      a thoracostomy tube. The control group consisted of 51 consecutive patients who
      underwent the same thoracoscopic procedures alone for primary spontaneous
      pneumothorax between January 1992 and April 1994. RESULTS: There was no
      significant difference between the two groups in terms of demographic data,
      operative findings, and operation time. Chest pain was a common complaint after
      minocycline pleurodesis, but the total doses of requested analgesics were
      comparable in both groups. The rate of prolonged air leaks was significantly
      lower in the minocycline group (7.0% vs 17.6%, p = 0.025). Patients treated with
      minocycline had shorter periods of postoperative chest drainage and
      hospitalization. The ipsilateral recurrence rate was also significantly lower in
      these patients (2.9% vs 9.8%, p = 0.033). CONCLUSIONS: Minocycline pleurodesis is
      a safe and convenient procedure that may improve the outcome and reduce the rate
      of recurrence after thoracoscopic treatment for primary spontaneous pneumothorax.
      A randomized control study may be needed to confirm the findings.

PMID- 14718421
TI  - Long-term beneficial effect of coronary artery bypass grafting in patients with
      COPD.
AB  - OBJECTIVE: This study assesses the impact of COPD on the long-term outcome of
      patients undergoing coronary artery bypass grafting (CABG). METHODS: Between 1991
      and 1993, 37 patients (5.68%) undergoing CABG had significant clinical COPD. They
      were compared to 37 matched control subjects. RESULTS: The patients in the COPD
      group had worse preoperative pulmonary function. More patients in this group were
      smokers, had more symptoms of shortness of breath, and had more preoperative
      arrhythmia. A total of 13 patients died in the COPD group compared with 3
      subjects in the control group during 8.6 +/- 2 years (mean +/- SD) of follow-up
      with arrhythmia being the major cause of death (62%). Actuarial survival at 9
      years was 92% for the control group vs 65% for the COPD group (p = 0.005). The
      rate of readmissions during mid-term follow-up (13.8 +/- 7.2 months) was higher
      in the COPD group, and more patients in this group described their quality of
      life as worse than before the operation (37% vs 3%, p < 0.001). At late follow
      up, all survivors in the COPD group had an improved quality of life. Cox
      regression analysis identified older age and lower FEV(1) as independent
      predictors of late death. Pulmonary function returned to baseline in the control
      group and improved to above baseline in the patients with COPD. CONCLUSIONS:
      Patients with significant COPD have a higher risk after CABG compared to patients
      without COPD. Nevertheless, when assessing the natural history of patients with
      COPD, it seems those who undergo CABG benefit from the operation.

PMID- 14718422
TI  - Risk and severity of COPD is associated with the group-specific component of
      serum globulin 1F allele.
AB  - BACKGROUND: The finding that only 15 to 20% of cigarette smokers acquire COPD
      suggests that there is a genetic predisposition to the disease. Genetic
      polymorphism of the group-specific component of serum globulin (Gc-globulin),
      also known as vitamin-D-binding protein, is considered one of the candidates for
      the susceptibility to COPD. However, the role of Gc-globulin polymorphism in the
      development of COPD remains inconclusive. STUDY OBJECTIVE: s: To determine
      whether Gc-globulin gene polymorphism plays a role in the development of COPD in
      the Japanese population, and whether it is associated with the physiologic
      deterioration in COPD, and its radiologically detectable correlates. DESIGN:
      Association study. SUBJECTS AND METHODS: One hundred three patients with COPD and
      88 healthy smokers sampled from the Japanese population were genotyped for Gc
      globulin by the restriction fragment-length polymorphism method. Based on the
      results of the genotyping, we investigated the relationship between Gc-globulin
      polymorphism and a physiologic/radiologic indicator of lung function, namely, the
      annual decline of FEV(1) (dFEV(1)) in 86 patients with COPD and 21 healthy
      smokers. Additionally, high-resolution CT parameters such as low-attenuation area
      percentage (LAA%) and average CT number (mean CT score) were measured in 85
      patients with COPD. RESULTS: There was an increased proportion of Gc*1F
      homozygotes in the patients with COPD (32%) compared with the healthy smokers
      (17%) [p = 0.01; odds ratio, 2.3; 95% confidence interval, 1.2 to 4.6]. Patients
      with COPD and the Gc*1F allele showed a larger dFEV(1) (p = 0.01), higher
      frequency with LAA% > 60% (p = 0.01), and lower mean CT score than patients
      without this allele (p = 0.03). CONCLUSION: Gc-globulin polymorphism is
      significantly associated with susceptibility to COPD, and also with the severity
      of the disease.

PMID- 14718423
TI  - Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients
      with COPD.
AB  - BACKGROUND: Previous studies have shown that the inflammatory response to
      cigarette smoking differs between smokers who acquire COPD and those who do not,
      and the CD8(+) T- lymphocytes have been identified as a key player in this
      response. OBJECTIVE: To investigate the cytotoxic activity and perforin
      expression of CD8(+) lymphocytes in the airway lumen of patients with COPD.
      METHODS: Thirty-six male smokers with COPD, 25 male smokers without COPD, and 10
      healthy nonsmokers participated in the study. T-lymphocytes of induced sputum
      samples were labeled with appropriate monoclonal antibodies and measured using
      flow cytometry. The cytotoxic activity of CD8(+) cells was defined by incubating
      them with specific target cells (K562). RESULTS: The percentage and the total
      number of CD8(+) lymphocytes were significantly higher in COPD smokers compared
      to non-COPD smokers (p = 0.01 and p = 0.005, respectively) or to healthy
      nonsmokers (p = 0.02 and p = 0.01, respectively). Perforin expression in CD8(+)
      cells was significantly higher in smokers with COPD compared to the other two
      groups (p = 0.001). Increased cytotoxic activity of T cells was also observed in
      induced sputum of patients with COPD in comparison to the other two groups.
      CONCLUSION: CD8(+) cells are not only increased in number in sputum samples of
      smokers with COPD but are highly activated, expressing high levels of perforin.
      These findings suggest that CD8(+) T-lymphocytes play a significant role in the
      inflammatory process of COPD.

PMID- 14718424
TI  - Comparison of continuous and discrete measurements of dyspnea during exercise in
      patients with COPD and normal subjects.
AB  - STUDY OBJECTIVES: The objectives of this study were as follows: (1) to compare
      results of the discrete and the continuous methods for measuring breathlessness;
      (2) to examine test-retest reliability; (3) and to test the hypothesis that
      patients with COPD have higher slopes and lower x-intercepts and absolute
      thresholds for power production, oxygen consumption (O(2)), and minute
      ventilation as independent variables and breathlessness ratings as the dependent
      variable, as compared with healthy subjects. DESIGN: Visit 1 (familiarization)
      and visit 2 and visit 3 (2 days apart) with randomized assignment of the discrete
      and continuous methods for subjects rating breathlessness during cycle ergometry.
      SETTING: Cardiopulmonary exercise laboratory in a university medical center.
      PARTICIPANTS: Twenty-four patients with COPD (mean age, 66 +/- 8 years [+/- SD])
      and 24 healthy subjects (mean age, 66 +/- 10 years). INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Ratings of breathlessness on the Borg scale on cue with
      subjects moving and pressing the computer mouse button to indicate a rating
      (discrete method) or by moving the position of the mouse to adjust a vertical bar
      to indicate a change in breathlessness (continuous method). There were no
      significant differences in results between visit 2 and visit 3. Although peak
      exercise variables were similar with the discrete and continuous methods, both
      groups provided significantly more ratings of breathlessness with the continuous
      method. Patients with COPD exhibited higher slopes, lower x-intercepts, and lower
      absolute thresholds (breathlessness rating >/==" BORDER="0"> 0.5 ["just
      noticeable"] on the Borg scale) for power production and O(2)-breathlessness
      compared with healthy subjects (p < 0.05). CONCLUSIONS: Elderly patients with
      COPD and healthy subjects are able to use the continuous method successfully.
      Reliability is excellent for both methods. The continuous method provides a
      greater number of breathlessness ratings over the course of exercise, and allows
      the clinician to calculate an absolute threshold and just-noticeable differences.
      Regression parameters and absolute thresholds discriminate between patients with
      COPD and healthy subjects.

PMID- 14718425
TI  - Ethnicity and skin test reactivity to aeroallergens among asthmatic children in
      Connecticut.
AB  - OBJECTIVES: To examine the relationship between ethnicity and sensitization to
      allergens among children with asthma living in urban and suburban areas of
      Connecticut. STUDY DESIGN: Cross-sectional study. STUDY POPULATION: A total of
      791 children with mild-to-severe asthma who received their medical care in the
      city of Hartford. RESULTS: Puerto Rican ethnicity was associated with skin test
      reactivity (STR) to cockroach (odds ratio [OR], 3.3; 95% confidence interval
      [CI], 1.7 to 6.4), STR to dust mite (OR, 1.7; 95% CI, 1.2 to 2.4), STR to mixed
      grass pollen (OR, 1.7; 95% CI, 1.1 to 2.7), and STR to mugwort/sage (OR, 2.4; 95%
      CI, 1.4 to 4.1). African-American ethnicity was associated with STR to four
      outdoor allergens (ie, mixed tree pollen [OR, 2.3; 95% CI, 1.3 to 3.9], mixed
      grass pollen [OR, 2.7; 95% CI, 1.6 to 4.8], mugwort/sage [OR, 3.1; 95% CI, 1.6 to
      6.0], and ragweed [OR, 2.1; 95% CI, 1.2 to 3.8]). Among all children, STR to
      outdoor allergens was strongly associated with the extent of allergen
      sensitization. As an example, children sensitized to mixed grass pollen had 34.7
      times higher odds of having at least four positive skin tests to other allergens
      than nonsensitized children (95% CI for OR, 15.6 to 77.0). CONCLUSIONS: Our
      findings suggest that Puerto Rican ethnicity is associated with an increased risk
      of sensitization to indoor and outdoor allergens among children with asthma, and
      that allergy skin testing should be performed more often as part of the
      management of asthma in African-American children and in Puerto Rican children in
      the United States.

PMID- 14718426
TI  - Measuring health-related quality of life in adults during an acute asthma
      exacerbation.
AB  - BACKGROUND: Acute severe asthma can be distressing for patients. It is important
      to be able to identify the causes of the distress so that these can receive
      attention in conjunction with the conventional treatment of the airways. STUDY
      OBJECTIVE: To modify the Asthma Quality of Life Questionnaire (AQLQ) for
      evaluating patients with acute severe asthma and to test the measurement
      properties of the Acute Asthma Quality of Life Questionnaire (Acute AQLQ).
      METHODS: The Acute AQLQ contains the symptom and emotional function items of the
      AQLQ (n = 11), which are capable of changing over short periods of time. The
      measurement properties were tested during a clinical trial to compare formoterol
      and salbutamol in the treatment of acute severe asthma in hospital emergency
      departments. RESULTS: The 88 patients in the clinical trial provided evidence
      that the Acute AQLQ has high internal consistency (Cronbach alpha = 0.90) and is
      very responsive to change in status (p < 0.00001) with a responsiveness index of
      2.5. Correlations between the Acute AQLQ and other measures of clinical status
      provided evidence of the validity of the instrument. CONCLUSION: The Acute AQLQ
      has strong measurement properties and can be used with confidence to identify the
      problems that are distressing to patients during an acute asthma exacerbation and
      to evaluate the effectiveness of interventions.

PMID- 14718427
TI  - Extrathoracic expiratory flow limitation in obesity and obstructive and
      restrictive disorders: effects of increasing negative expiratory pressure.
AB  - BACKGROUND: The negative expiratory pressure (NEP) technique is used to detect
      intrathoracic expiratory flow limitation (EFL) in patients with respiratory
      disorders. Application of NEP may result in a sustained decrease of flow below
      control as a result of upper airway collapse, which may invalidate interpretation
      of the test. This response to NEP is common in patients with obstructive sleep
      apnea syndrome (OSAS). The prevalence of this phenomenon, however, has not been
      studied in healthy subjects and patients with obstructive and restrictive
      disorders without OSAS. PURPOSE: The purpose of this study was as follows: (1) to
      assess the effects of increasing NEP levels on upper airway patency, and (2) to
      determine the factors that predispose to intrathoracic flow limitation or upper
      airway collapse during NEP application in different postures in healthy nonobese
      and obese subjects, and in patients with obstructive and restrictive respiratory
      disorders. SUBJECTS: Fifty-six patients with obstructive airway disease (21
      patients with COPD, 16 patients with simple chronic bronchitis, and 19 patients
      with asthma) were compared with 47 patients with restrictive respiratory
      disorders, 20 nonobese and healthy subjects, and 9 obese subjects (body mass
      index > 30) without a history of snoring or OSAS. METHODS: NEP at levels of 5 cm
      H(2)O, 10 cm H(2)O, and 15 cm H(2)O were applied at the mouth immediately after
      the onset of tidal expiration while seated and supine. Intrathoracic EFL was
      defined as no change in expiratory flow over any portion of the immediately
      preceding control breath. Upper airway collapse or narrowing was detected when
      flows decreased below those of the control breath. RESULTS: Ten patients (18%)
      with obstructive airway disease (7 patients with COPD) exhibited EFL at NEP of 5
      cm H(2)O (4 patients were supine only, and 6 patients were both supine and
      sitting). No patient with restrictive disorders or healthy obese and nonobese
      subjects presented EFL at NEP of 5 cm H(2)O. In almost all subgroups, both seated
      and supine, subjects exhibited a transient decrease of flow below control
      immediately after the application of NEP in occasional breaths. As NEP increased,
      the number of subjects who exhibited this response in occasional breaths
      declined, while the number of subjects who displayed this pattern in all breaths
      increased. Conversely, there were very few subjects in each subgroup who
      exhibited a sustained decrease in flow below control in occasional breaths at NEP
      at 5 cm H(2)O, and only one healthy obese subject who displayed this response in
      all breaths in supine position only. CONCLUSIONS: In general, an increase in NEP
      resulted in only rare instances of sustained decrease in flow below control in
      all breaths. While transient decreases in flow exhibited immediately after the
      onset of NEP in all breaths are common and become more prevalent as NEP is
      increased beyond 5 cm H(2)O, there are only rare instances of sustained decrease
      in flow below control throughout expiration at all levels of NEP tested,
      indicating an appropriate upper airway dilator response that maintains patency.
      Thus, in subjects without OSAS, assessment of intrathoracic EFL with NEP is valid
      in almost all instances.

PMID- 14718428
TI  - Airway obstruction is common but unsuspected in patients admitted to a general
      medicine service.
AB  - STUDY OBJECTIVES: Obstructive lung disease (OLD) is a worldwide health problem
      with major impact on health and economics, and can be easily diagnosed by
      spirometry. Recent expert panels have emphasized the underreporting and
      underrecognition of this condition. The goal of this study was to measure the
      prevalence of airway obstruction in patients admitted to an urban teaching
      hospital and to determine the frequency of a diagnosis of OLD at admission or
      discharge. METHODS: Prospective study of 153 patients admitted to a medicine
      service at the Johns Hopkins Hospital in Baltimore, MD. Patients completed
      bedside spirometry and a questionnaire. RESULTS: Twenty-six percent of patients
      had airway obstruction (FEV(1)/FVC < 70%), including 6% with a very severe airway
      obstruction (FEV(1) < 30% predicted). At hospital discharge, a clinical diagnosis
      of OLD was present in only 33% of patients with mild airway obstruction (FEV(1) >
      70% predicted), 30% of patients with moderate airway obstruction (FEV(1) 50 to
      69% predicted), 33% of patients with severe airway obstruction (FEV(1) 30 to 49%
      predicted), and 89% of patients with very severe airway obstruction (FEV(1) < 30%
      predicted). Only 40% of patients with airway obstruction were receiving
      bronchodilator medication at hospital admission or discharge. CONCLUSIONS: Airway
      obstruction is common in hospitalized patients and is usually undiagnosed and
      untreated. Spirometry may be a useful component of the examination of
      hospitalized medical patients to identify OLD.

PMID- 14718429
TI  - Aldosterone excretion among subjects with resistant hypertension and symptoms of
      sleep apnea.
AB  - OBJECTIVE: The severity of obstructive sleep apnea (OSA) correlates with the
      difficulty of controlling BP. The mechanism, however, by which sleep apnea
      contributes to the development of resistant hypertension remains obscure. Having
      observed a high prevalence of OSA among hypertensive subjects with primary
      hyperaldosteronism, we hypothesized a possible association between sleep apnea
      and aldosterone excretion. DESIGN: In consecutive subjects referred to a
      university clinic for resistant hypertension, we prospectively determined plasma
      renin activity (PRA), plasma aldosterone concentration (PAC), and 24-h urinary
      aldosterone excretion during high dietary salt ingestion. In addition, all
      subjects completed the Berlin Questionnaire, a survey designed to identify
      subjects at risk of having sleep apnea. Primary hyperaldosteronism (PA) was
      defined as a PRA < 1.0 ng/mL/h and 24-h urinary aldosterone excretion > 12 micro
      g during high urinary sodium excretion (> 200 mEq/24 h). RESULTS: Of the 114
      subjects evaluated, 72 subjects had a high probability and 42 subjects had a low
      probability of having sleep apnea based on their responses to the Berlin
      Questionnaire. Subjects at high risk for sleep apnea were almost two times more
      likely to have PA diagnosed (36 vs 19%, p < 0.05), tended to have lower PRA (1.2
      +/- 1.8 ng/mL/h vs 1.9 +/- 4.1 ng/mL/h), and had significantly greater 24-h
      urinary aldosterone excretion (13.6 +/- 9.6 micro g vs 9.8 +/- 7.6 micro g, p <
      0.05) compared to subjects at low risk of sleep apnea. CONCLUSION: These data
      provide evidence of increased aldosterone excretion in subjects with resistant
      hypertension and symptoms of sleep apnea. While the causality of this association
      is unknown, it is hypothesized that sleep apnea contributes to the development of
      resistant hypertension by stimulating aldosterone excretion.

PMID- 14718430
TI  - Lack of efficacy for a cervicomandibular support collar in the management of
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: The effect of therapy using a cervicomandibular support collar
      (CMSC) to manage obstructive sleep apnea (OSA) was compared with standard
      therapy, nasal continuous positive airway pressure (nCPAP). DESIGN: Subjects
      received treatment with CMSC or nCPAP each for 1 month in random order. The study
      was analyzed on an intention-to-treat basis. SETTING: Tom McKendrick Sleep
      Laboratory, Dunedin Hospital. PARTICIPANTS: Ten adult subjects with mild-to
      moderate OSA (apnea-hypopnea index [AHI], 24 +/- 13/h slept [mean +/- SD])
      completed the study. INTERVENTIONS: The CMSC was designed to prevent mandibular
      movement and hold the head in slight extension, thus preventing the postural
      changes that might contribute to OSA. Positioning of the CMSC was confirmed by an
      externally applied cervical range of motion (CROM) instrument and by
      cephalometry. Subjects were carefully instructed in the use of each device and
      completed a symptom diary. After 1 month, subjects underwent polysomnography with
      each of the allocated devices in situ, and symptom questionnaires were
      administered. MEASUREMENTS AND RESULTS: Treatment success (AHI </= 10/h slept)
      with CMSC was achieved in only 2 of 10 subjects, partial success (AHI > 10/h to
      </= 15/h slept) was achieved in 2 subjects, and in 6 of 10 subjects there was no
      benefit. In contrast, treatment success was achieved in 7 of 10 subjects
      receiving nCPAP. Mean AHI was 29.4 +/- 13.4/h at baseline, 26.9 +/- 17.2/h slept
      with CMSC, and 9.9 +/- 8.0/h slept with nCPAP (p = 0.001). No significant
      differences in sleep architecture or sleep efficiency were achieved using nCPAP
      compared to CMSC. The efficacy of the CMSC in maintaining the desired head
      position was confirmed by cephalometry and the CROM instrument. CONCLUSIONS: Our
      results, although negative, provide important evidence that control of head and
      neck posture, perhaps adopted as a second-line treatment, is not helpful in the
      management of OSA. It appears that other anatomic and physiologic factors have a
      dynamic overriding influence on upper airway closure compared to simple skeletal
      relationships.

PMID- 14718431
TI  - A community study of sleep-disordered breathing in middle-aged Chinese women in
      Hong Kong: prevalence and gender differences.
AB  - STUDY OBJECTIVES: To investigate the prevalence of sleep-disordered breathing
      (SDB) and obstructive sleep apnea syndrome (OSAS) in community-based, middle-aged
      Chinese women, and to compare the differences between gender with a similar study
      in men. DESIGN: A cross-sectional study conducted in Hong Kong from 1998 to 2000.
      SETTING: Sleep questionnaires were distributed to women (30 to 60 years old) in
      three offices and two community centers. All were invited to undergo full
      polysomnography in a sleep laboratory. PARTICIPANTS: Questionnaires were
      distributed to 1,532 women, and 854 questionnaires were returned. Polysomnography
      was conducted in 106 respondents. MEASUREMENTS AND RESULTS: Conservative
      estimated prevalence of SDB (apnea-hypopnea index [AHI] > = 5) and OSAS (AHI > or
      = 5 plus excessive daytime sleepiness [EDS]) were 3.7% and 2.1%, respectively.
      Age-specific prevalence of OSAS was 0.5%, 2.2%, and 6.1% in the 30- to 39-year
      old, 40- to 49-year-old, and 50- to 60-year-old age groups, respectively.
      Stepwise multiple logistic regression analysis identified body mass index (BMI)
      and age as predictors of SDB. Compared to Chinese men, the prevalence of SDB and
      OSAS in women was lower, but the gender difference decreased with age. The AHI of
      affected women was also significantly lower despite comparable BMI. Compared to
      men, women with SDB had same degree of self-reported snoring and a similar degree
      of EDS despite the lower AHI. CONCLUSIONS: This study demonstrated an estimated
      prevalence of OSAS at 2.1% among middle-aged Chinese women in Hong Kong, with a
      12-fold rise from the fourth to the sixth decade of life. BMI and age were
      significant independent predictors of SDB. Compared to men, women with SDB had
      lower AHIs, despite similar BMIs.

PMID- 14718432
TI  - Diffuse cystic lung diseases: correlation between radiologic and functional
      status.
AB  - BACKGROUND: High-resolution CT (HRCT) scanning plays an important role in the
      diagnosis of diffuse cystic lung diseases (DCLDs). However, its role in the
      clinical evaluation of patients affected by DCLD has not yet been well-clarified.
      At present, pulmonary function tests are the only methods available for the
      evaluation of lung impairment due to these diseases, but their sensitivity and
      reliability are still limited. PURPOSE: The aim of this study was to correlate
      the quantitative score of cystic-aerial lesions obtained by a HRCT density mask
      (DM) software with pulmonary function data in DCLDs. METHODS: Spirometry, lung
      volumes, diffusion capacity, arterial blood gas (ABG) analysis, 6-min walking
      test (6-MWT), and HRCT with DM quantitative evaluation were performed in a cohort
      of 25 patients (lymphangioleiomyomatosis [LAM], 13 patients; Langerhans cells
      histiocytosis [LCH], 12 patients). Linear regression was used for the statistical
      analysis. The sum and mean of the air-trapping percentages at three different
      levels of DM study (ie, aortic arch, left lower lobe bronchus origin, and 2 cm
      from the diaphragmatic muscle), and various functional parameters and exercise
      performance values were matched for the analysis. RESULTS: An obstructive pattern
      was present in 13 patients (52%; LCH group, 8 patients; LAM group, 5 patients). A
      predominant restrictive pattern was detected only in three patients (12%; LCH
      group, two patients; LAM group, one patient). Nine patients (36%) walked < 350 m,
      and 14 of 23 patients (61%) had a significant decrease in arterial oxygen
      saturation during exercise (> 4 U). The results of DM quantitative study (sum and
      mean) significantly correlated with FVC (r = - 0.56; p < 0.001), FEV(1)/vital
      capacity (r = - 0.94; p < 0.002), midexpiratory phase of forced expiratory flow
      (r = - 0.84; p < 0.05), FEV(1) (r = - 0.82; p < 0.05), and diffusing capacity of
      the lung for carbon monoxide (r = - 0.82; p < 0.05), bronchial airway resistance
      (r = 0.79; p < 0.05), and distance walked on the 6-MWT (r = - 0.53; p < 0.05). No
      significant correlation was found with the results of ABG analysis. CONCLUSIONS:
      In DCLDs, HRCT scans with quantitative assessment performed by a DM software
      showed a very good correlation with functional parameters. Therefore, DM could be
      considered, in combination with a complete functional assessment, in the initial
      evaluation of patients affected by DCLDs. However, further studies are needed to
      assess its usefulness in the follow-up of these patients.

PMID- 14718433
TI  - A phase I trial of intranasal Moli1901 for cystic fibrosis.
AB  - BACKGROUND: The peptide drug Moli1901 activates an alternative chloride channel
      that is present in cystic fibrosis (CF) nasal and airway epithelia. Doing so
      bypasses the dysfunctional CF transmembrane regulator. STUDY OBJECTIVE: To
      determine whether intranasal Moli1901 is safe, tolerable, and will induce
      chloride transport in healthy volunteers and CF subjects. DESIGN: A single-blind
      (to the participant), randomized, placebo-controlled, dose-escalation study of
      intranasal Moli1901 was performed in four healthy non-CF participants and four
      participants with CF. Drug or placebo was administered by intranasal superfusion,
      and nasal potential difference responses were continuously monitored during
      sequential dose escalations at 1-min intervals from 0.01 through 10 micro mol/L.
      RESULTS: Neither Moli1901 nor placebo were associated with visible changes such
      as edema, erythema, drainage, secretions, or ulcer formation. No elevations in
      lactate dehydrogenase, albumin, or cell counts were observed in nasal lavage
      fluid after administration. No clinically significant changes in FEV(1) or other
      toxicity parameters occurred. Changes in the nasal potential difference (NPD)
      induced by chloride-free, amiloride-containing Ringers solution and by subsequent
      superfusion with the same solution plus 10 micro mol/L isoproterenol were
      consistent with both an acute and a sustained change in chloride transport in
      response to Moli1901. A similar analysis of NPD in the four CF participants
      demonstrated an acute response that resolved more quickly. A dose-response
      relationship to Moli1901 was observed in non-CF participants, but a greater range
      of variability within the CF participants contributed to the lack of a clear dose
      response relationship in this group. CONCLUSION: Moli1901 stimulates chloride
      transport in normal and CF nasal epithelia in vivo, but may have a shorter
      duration of action in CF participants.

PMID- 14718434
TI  - The repeatability of forced expiratory volume measurements in adults with cystic
      fibrosis.
AB  - STUDY OBJECTIVE: To determine the repeatability of measurements of FEV(1) in
      adults with lung disease due to cystic fibrosis (CF). DESIGN: Single cohort study
      nested within a randomized controlled trial. SETTING: Adult CF of a university
      teaching hospital. Subjects were participants in a randomized trial of an
      experimental mucolytic drug. PATIENTS: Twenty-one adults (mean age, 27.5 +/- 9.2
      years [+/- SD]) with CF and mild-to-moderate airflow obstruction (FEV(1) 70 +/-
      15% predicted). Patients were in clinically stable condition prior to and during
      the study. INTERVENTIONS: Repeated FEV(1) measurements were obtained at specific
      times of the day for 9 consecutive days, for a total of 31 measurements from each
      subject. Statistical measures of repeatability were calculated. Variation over
      the course of 1 day and variation from 1 day to the next were examined
      separately. MEASUREMENTS AND RESULTS: For day-to-day FEV(1) measurements, the
      within-subject SD was 0.145 L (4.5% of predicted), indicating greater variation
      compared to values previously established in normal subjects. The coefficient of
      repeatability indicated that day-to-day measurements could differ by as much as
      13% of predicted in the absence of clinical change. For measurements within a
      single day, variation was not observed to be greater than normal. CONCLUSIONS: In
      adults with CF, day-to-day variation in FEV(1) measurements is greater than
      normal and similar to that seen in other obstructive lung diseases. Changes in
      FEV(1) over time in adults with CF can likely be interpreted using the same
      criteria that apply to asthma or COPD.

PMID- 14718435
TI  - Clinical implications of appearance of pleural fluid at thoracentesis.
AB  - STUDY OBJECTIVES: The aims of this study were to describe the different
      appearances of pleural fluid during thoracentesis and their frequency in relation
      to diagnosis, and to evaluate the causes and clinical implications of bloody
      pleural effusions. SETTING: Tertiary care, university-affiliated hospital.
      SUBJECTS AND METHODS: Seven hundred fifteen patients with pleural effusion were
      prospectively assessed from December 1991 to December 1997. INTERVENTIONS: The
      appearance of the fluid was assessed in a glass assay tube containing 10 mL of
      pleural fluid. RESULTS: The most common presentations were serous and blood
      tinged, with 80% of the fluids fitting into one of these categories. The most
      frequent cause of watery fluid was transudate, although most transudates were
      classified as serous effusions. There were 59 bloody and 656 nonbloody pleural
      fluids. The most common cause of bloody pleural effusion (BPE) was malignancy
      (47%). Fluid with a bloody appearance slightly increased the probability of
      malignancy in our series (odds ratio [OR], 1.73; 95% confidence interval [CI],
      1.01 to 2.94; p = 0.04). Nevertheless, only 11% of the neoplastic effusions were
      BPE. Other common causes of BPE were posttraumatic (12%) or parapneumonic (10%)
      pleural effusions. Tuberculosis and transudates were uncommon causes of BPE.
      Fluid that was bloody in appearance decreased the probability for both diseases
      (OR, 0.15; 95% CI, 0.04 to 0.57; p = 0.003 and OR, 0.25; 95% CI, 0.06 to 0.95; p
      = 0.04, respectively). CONCLUSIONS: Serous and blood tinged were the most common
      presentations of pleural fluid at thoracentesis. Almost half of BPEs were
      secondary to neoplasms, but only 11% of the neoplastic effusions were BPEs. Other
      common causes of BPE were parapneumonic and posttraumatic.

PMID- 14718436
TI  - Tumor necrosis factor-alpha in pleural fluid: a marker of complicated
      parapneumonic effusions.
AB  - STUDY OBJECTIVES: We sought to determine whether pleural fluid tumor necrosis
      factor (TNF)-alpha is a more accurate parameter to identify nonpurulent
      complicated parapneumonic effusion (CPPE) than the classical chemistries, namely
      pH, glucose, or lactate dehydrogenase (LDH). METHODS: We studied 80 consecutive
      patients with parapneumonic effusions (35 with uncomplicated parapneumonic
      effusion [UPPE], 23 with nonpurulent CPPE, and 22 with empyema). Concentrations
      of standard biochemical parameters together with TNF-alpha were measured in
      pleural fluid, the latter by using an immunoenzymometric assay. RESULTS: Pleural
      TNF-alpha was significantly higher in CPPE (133.0 pg/mL) and empyema (142.2
      pg/mL) than in UPPE (39.1 pg/mL). A cut-off value of 80 pg/mL for pleural TNF
      alpha resulted in a sensitivity, specificity, and area under receiver operating
      characteristic curve (AUC) of 78%, 89%, and 0.87, respectively, for the diagnosis
      of nonpurulent CPPE. A multivariate analysis selected both pleural TNF-alpha > or
      = 80 pg/mL and LDH > or = 1,000 U/L (sensitivity, 74%; AUC = 0.86), but excluded
      pleural glucose < or = 60 mg/dL (sensitivity, 39%; AUC = 0.82) and pH < or = 7.20
      (sensitivity, 41%; AUC = 0.78), for identifying the need for drainage. The
      combined sensitivity of pleural fluid TNF-alpha and LDH was found to be 91%.
      CONCLUSIONS: Pleural TNF-alpha may contribute to the identification of patients
      with nonpurulent CPPE with at least the same diagnostic accuracy, if not better,
      than the use of pH, glucose, or LDH.

PMID- 14718437
TI  - Pulmonary nodules in lung transplant recipients: etiology and outcome.
AB  - BACKGROUND: The pulmonary nodule (PN) poses a diagnostic and therapeutic
      challenge in the immunocompromised host. Common causes of PNs in lung transplant
      (LT) recipients include bacterial or fungal infections and posttransplant
      lymphoproliferative disorder (PTLD). However, experience in diagnosis and
      management of PNs is limited. METHODS: Two hundred thirty-four LTs were performed
      between February 1990 and December 2000. Medical records of all patients with PNs
      were reviewed retrospectively. Data on presentation, radiographic features,
      diagnostic methods, therapy, and outcome were collected and analyzed. RESULTS:
      Twenty-three patients had PNs after a follow-up of 20.1 +/- 20.1 months (mean +/-
      SD). The mean age was 45.5 +/- 14.4 years, with a male:female ratio of 17:6.
      Thirteen patients received single LT, 9 patients received bilateral LT, and 1
      patient received heart-LT. Cough and dyspnea were the most common symptoms at
      presentation, and PNs were better detected by CT than chest radiography. Solitary
      PNs were due to bronchogenic carcinoma and PTLD, while multiple PNs were due to
      invasive pulmonary aspergillosis (IPA), cytomegalovirus pneumonitis,
      bronchiolitis obliterans, and metastatic carcinoma. Bronchoscopy with BAL and
      transbronchial lung biopsy was the usual method of diagnosis (n = 17, 74%), and
      our mortality rate was 70%. CONCLUSION: PNs are not uncommon in patients
      following LT. The majority were due to IPA and PTLD. Prophylaxis with
      itraconazole against Aspergillus, and acyclovir for Epstein-Barr virus-negative
      LT recipients, serial CT and surveillance bronchoscopy for early detection of
      Aspergillus infections, and rituximab therapy for PTLD could improve the outcome
      of these patients.

PMID- 14718438
TI  - Functional analysis in single-lung transplant recipients: a comparative study of
      high-resolution CT, 3He-MRI, and pulmonary function tests.
AB  - OBJECTIVE: To develop and evaluate a postprocessing tool to quantify ventilated
      split-lung volumes on the basis of (3)He-MRI and to apply it in patients after
      single-lung transplantation (SLTX). High-resolution CT (HRCT) was employed as a
      reference modality providing split air-filled lung volumes. Lung volumes derived
      from pulmonary function test results served as clinical parameters and were used
      as the "gold standard." MATERIAL AND METHODS: Eight patients (mean age, 54 years)
      with emphysema and six patients (mean age, 58 years) with idiopathic pulmonary
      fibrosis. All patients were evaluated following SLTX. HRCT was performed during
      inspiration (slice thickness, 1 mm; increment, 10 mm). For correlation with (3)He
      MRI, HRCT images were reconstructed in coronal orientation to match the same
      anatomic levels. Aerated lung was determined by threshold-based segmentation of
      CT. (3)He-MRI was performed on a 1.5-T scanner using a two-dimensional, fast low
      angle shot sequence in coronal orientation covering the whole lung after
      inhalation of a 300-mL bolus of hyperpolarized (3)He gas followed by normal room
      air for the rest of the tidal volume. Lung segmentation on (3)He-MRI was done
      using different thresholds. RESULTS: In emphysematous patients, (3)He-MRI showed
      excellent correlation (r = 0.9) with vital capacity, while CT correlated (r =
      0.8) with total lung capacity. (3)He-MRI correlated well with CT (r > 0.8) for
      grafts and native fibrotic lungs. In emphysematous lungs, MRI showed a good
      correlation (r = 0.7) with the nonemphysematous lung volume from CT. Increasing
      thresholds in (3)He-MRI reveal differences between aerated and ventilated lung
      areas with a different distribution in emphysema and fibrosis. CONCLUSIONS: (3)He
      MRI is superior to CT in emphysema to demonstrate ventilated lung areas that
      participate in gas exchange. In fibrosis, (3)He-MRI and CT have a similar impact.
      The decrease pattern and the intraindividual ratio between ventilation of native
      and transplanted lungs will have to be investigated as a new surrogate for the
      ventilatory follow-up in patients undergoing SLTX.

PMID- 14718439
TI  - Cerebral oxygenation during exercise in cardiac patients.
AB  - BACKGROUND: Until recently, compensatory mechanisms have been believed to
      regulate adequately cerebral blood flow in humans. However, this has been called
      into question by a series of new investigations suggesting that patients with
      left ventricular dysfunction suffer from cerebral hypoperfusion. We compared
      cerebral oxygenation during incremental exercise between patients with valvular
      heart disease and normal subjects. METHODS: Thirty-three patients with valvular
      disease and 33 normal subjects performed a symptom-limited incremental exercise
      test using a cycle ergometer. Oxyhemoglobin at the forehead was continuously
      monitored during exercise using near-infrared spectroscopy. Respiratory gas
      measurements were performed on a breath-by-breath basis. RESULTS: The increase in
      oxyhemoglobin during exercise was significantly lower in the patients with
      valvular disease than in normal subjects. The change in oxyhemoglobin during
      exercise (DeltaO(2)Hb) at the forehead was negatively correlated with the slope
      of the increase in minute ventilation to the increase in carbon dioxide output
      (DeltaE/DeltaCO(2)), and positively correlated with the peak oxygen uptake
      (O(2)), gas exchange threshold (GET), and slope of the increase in O(2) to the
      increase in the work rate (DeltaO(2)/DeltaWR). Among the patients with valvular
      disease, 15 patients showed a decrease in oxyhemoglobin at the forehead during
      exercise. When compared with the patients with increased oxyhemoglobin, those
      with decreased levels exhibited a higher DeltaE/DeltaCO(2) and a lower peak O(2),
      GET, and DeltaO(2)/DeltaWR. CONCLUSIONS: The present findings strongly suggest
      that cerebral oxygenation during exercise is dependent on the cardiovascular and
      pulmonary systems. The study also indicated the presence of cerebral
      hypoperfusion during exercise in cardiac patients whose cardiac output fails to
      increase normally.

PMID- 14718440
TI  - Deep vein thrombosis among patients entering cardiac rehabilitation after
      coronary artery bypass surgery.
AB  - BACKGROUND: Little information is available about the prevalence of deep vein
      thrombosis (DVT) after discharge from cardiac surgery units and its impact on
      rehabilitation programs. OBJECTIVES: To estimate the rate of DVT, in relation to
      different thromboprophylaxis strategies, in patients with a recent coronary
      artery bypass graft (CABG) entering cardiac rehabilitation. METHODS: Two hundred
      seventy consecutive patients admitted to three rehabilitation facilities after
      CABG surgery from 19 cardiac surgery units (male patients, 81%; mean +/- SD age,
      64 +/- 9 years; interval after operation, 4 to 19 days) underwent serial leg
      venous ultrasound examination on admission to three rehabilitative units.
      RESULTS: At admission, antiplatelet treatment was present in all patients except
      10 with absolute contraindications. In 171 patients (63%), heparin prophylaxis
      (low-molecular-weight heparin once daily, 87%; unfractionated heparin twice
      daily, 13%) was reported, limited to the early postoperative period (< or = 3
      days) in 102 patients (38%). DVT was detected in 47 patients (17.4%). The rate of
      proximal and isolated distal DVT was 2.6% (7 cases) and 14.8% (40 cases),
      respectively. DVT was complicated in two cases (0.7%) by symptomatic pulmonary
      embolism, fatal in one case (0.4%). Clots were found in the leg contralateral to
      the saphenous vein harvest site in half of all DVT cases. Forty-three DVT cases
      (91%) were diagnosed at admission, while serial ultrasound testing allowed
      diagnosis of an additional 4 distal DVT cases. At multivariate analysis, female
      sex (p < 0.001) and length of stay in the surgery unit > 8 days (p < 0.05) were
      independently associated with risk of DVT in the rehabilitation setting. The
      adoption of heparin prophylaxis until discharge predicted the absence of DVT
      after adjustment for immobility (p < 0.05). CONCLUSIONS: This study showed a high
      rate of DVT in patients entering cardiac rehabilitation after CABG surgery.
      Wearing unilateral graded compression stockings after CABG surgery had limited
      efficacy, as clots were often localized in legs contralateral to the saphenous
      vein harvest site.

PMID- 14718441
TI  - The role of open-lung biopsy in ARDS.
AB  - STUDY OBJECTIVES: The role of open-lung biopsy in ARDS has been questioned due to
      potentially high morbidity and low diagnostic yield. The goals of this study were
      to better define the frequency of unexpected diagnoses made by open-lung biopsy,
      the frequency biopsy results lead to a change in clinical management, and the
      frequency of procedural complications. DESIGN: Case series. SETTING: A large
      tertiary referral center. PATIENTS: All individuals with available records
      undergoing open-lung biopsy between 1989 and 2000 for evaluation of ARDS based on
      the American-European Consensus Conference definition. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: The mean age in this cohort of 57 patients was 53 years
      (SD, 18 years) with PaO(2)/fraction of inspired oxygen ratio of 145 mm Hg (SD, 61
      mm Hg) at the time of biopsy. A pathologic diagnosis other than diffuse alveolar
      damage or fibroproliferation was found in 60% of patients. The most common
      alternative diagnoses were infection (n = 8), alveolar hemorrhage (n = 5), and
      bronchiolitis obliterans organizing pneumonia (n = 5). Alternative diagnoses were
      as frequent in immunocompetent as immunosuppressed hosts (60% vs 59%,
      respectively). Biopsy results led to a change in management in the majority of
      patients, with addition of specific therapy in 60% and withdrawal of unneeded
      therapy in 37%. Although the overall complication rate was 39%, major
      complications occurred in only 7% of cases. No deaths were attributable to the
      procedure. CONCLUSIONS: In selected patients with clinical ARDS, open-lung biopsy
      can be performed safely, often reveals an unsuspected diagnosis, and frequently
      leads to alterations in therapy.

PMID- 14718442
TI  - Polymorphism in the surfactant protein-B gene, gender, and the risk of direct
      pulmonary injury and ARDS.
AB  - STUDY OBJECTIVE: Major risk factors for ARDS have been identified. However, only
      a minority of patients with such risks develops ARDS. It is likely that, given
      the same type and degree of insult, there are heritable determinants of
      susceptibility to ARDS. To investigate the possibility of variable genetic
      susceptibility to ARDS, we examined the association between ARDS and a
      polymorphism in intron 4 of the surfactant protein-B (SP-B) gene. DESIGN: Nested
      case-control study conducted from September 1999 to March 2001. SETTING: Four
      adult medical and surgical ICUs at a tertiary academic center. PATIENTS: One
      hundred eighty-nine patients meeting study criteria for a defined risk factor for
      ARDS were enrolled and prospectively followed. MEASUREMENTS AND RESULTS: Seventy
      two patients (38%) developed ARDS. After stratification by gender and adjustment
      for potential confounders, there was a significantly increased odds for women
      with the variant SP-B gene to develop ARDS compared to women homozygous for the
      wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to
      18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly
      increased odds of having a direct pulmonary injury such as aspiration or
      pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for
      ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or
      direct pulmonary injury was found for men. CONCLUSION: The variant polymorphism
      of the SP-B gene is associated with ARDS and with direct pulmonary injury in
      women, but not in men. Further study is needed to confirm the association between
      the variant SP-B gene, and gender, ARDS, and direct pulmonary injury.

PMID- 14718443
TI  - Alveolar granulocyte colony-stimulating factor and alpha-chemokines in relation
      to serum levels, pulmonary neutrophilia, and severity of lung injury in ARDS.
AB  - OBJECTIVES: To determine granulocyte colony-stimulating factor (G-CSF),
      epithelial neutrophil-activating peptide (ENA)-78, and interleukin (IL)-8 in BAL
      fluid (BALF), epithelial lining fluid (ELF), and serum for establishing the
      concentration gradient of G-CSF, ENA-78, and IL-8 between the blood and the
      alveolar space in ARDS and acute lung injury (ALI); and to evaluate the
      relationship of G-CSF, IL-8, and ENA-78 to pulmonary neutrophilia and severity of
      lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU.
      PATIENTS: Nineteen patients with ARDS and 10 patients with ALI. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: BAL and blood sampling simultaneously within
      12 h and 24 h after onset of ARDS/ALI; G-CSF was detected in BALF in 18 of 19
      patients with ARDS, in 7 of 10 patients with ALI, and in all serum samples. G-CSF
      in BALF and serum was significantly higher in ARDS than in ALI. ENA-78 was
      detected in BALF in 14 of 19 patients with ARDS, in 8 of 10 patients with ALI,
      and in serum of all patients. Levels in BALF and serum were not different between
      ARDS and ALI. IL-8 was detected in all patients; concentrations in BALF in ARDS
      were significantly higher than in ALI. Concentrations of G-CSF, ENA-78, and IL-8
      in ELF were significantly higher than in serum. G-CSF in BALF and serum and IL-8
      in BALF correlated positively with pulmonary neutrophilia. G-CSF in serum and IL
      8 in BALF correlated negatively with PaO(2)/fraction of inspired oxygen (FIO(2))
      ratio. However, ENA-78 did not show a correlation with neutrophil count or with
      PaO(2)/FIO(2) ratio. CONCLUSIONS: G-CSF may be pathophysiologically important for
      accumulation and activation of neutrophils in ARDS. Local G-CSF production is the
      likely driving force for neutrophils rather than elevation of circulating levels.
      In comparison to ENA-78, IL-8 seems to be the predominant neutrophil
      chemoattractant in the early phase of ARDS.

PMID- 14718444
TI  - Hospital and long-term outcome after tracheostomy for respiratory failure.
AB  - OBJECTIVE: To determine the patient characteristics, hospital course, hospital
      cost, posthospital survival, and functional outcome in a group of patients with
      tracheostomy for respiratory failure. DESIGN: Retrospective chart review combined
      with prospective evaluation of functional status. SETTING: An urban, tertiary
      care medical center. PATIENTS: Adult patients with tracheostomy for respiratory
      failure between January 1, 1998, and December 31, 2000. METHODS: Retrospective
      chart review and prospective administration of the Short Form-36 (SF-36) for
      health status outcome. RESULTS: Four hundred twenty-nine patients were studied.
      Hospital mortality was 19%. Only 57% of survivors were liberated from mechanical
      ventilation. At 100 days, 6 months, 1 year, and 2 years after discharge, 24%,
      30%, 36%, and 42% of hospital survivors had died, respectively. Patients
      liberated from mechanical ventilation and having their tracheostomy tubes
      decannulated had the lowest mortality (8% at 1 year); the mortality of ventilator
      dependent patients was highest (57%). Sixty-six patients completed the SF-36 for
      functional status. While emotional health was generally good, physical function
      was quite limited. Median hospital direct variable cost was $29,340. CONCLUSION:
      Overall survival and functional status are poor in patients with tracheostomy for
      respiratory failure. Patients who are liberated from mechanical ventilation and
      have their tracheostomy tubes removed have the best survival; however, it comes
      at a higher hospital cost and longer length of stay.

PMID- 14718445
TI  - Differential-display polymerase chain reaction identifies nicotinamide adenine
      dinucleotide-ubiquinone oxidoreductase as an ischemia/reperfusion-regulated gene
      in cardiomyocytes.
AB  - OBJECTIVE: Cardiac ischemia/reperfusion-induced oxidative damage often occurs in
      mitochondria. We identified differentially expressed genes in the canine heart
      after global cardiac ischemia/reperfusion injury was induced during
      cardiopulmonary bypass (CPB). METHODS: Differential-display polymerase chain
      reaction (ddPCR) was performed on cardiac tissue from canine hearts with or
      without global cardiac ischemia/reperfusion injury induced during CPB.
      Ischemia/reperfusion-associated mitochondrial injury was investigated at the
      protein level using various cardioplegic solutions and Western blot analysis.
      RESULTS: A mitochondrial protein nicotinamide adenine dinucleotide
      (NADH):ubiquinone oxidoreductase gene was identified on ddPCR. The
      NADH:ubiquinone oxidoreductase gene was up-regulated in canine hearts after 60
      min of global cardiac ischemia/reperfusion injury during CPB. Western blot
      analysis revealed that, after manipulation with different cardioplegic solutions,
      increased Bcl-2 expression and decreased cytochrome c expression were associated
      with cardiomyocytic apoptosis. CONCLUSIONS: The NADH:ubiquinone oxidoreductase
      gene is up-regulated during global cardiac ischemia/reperfusion injury during CPB
      in canines. To our knowledge, involvement of this gene in global cardiac
      ischemia/reperfusion injury during CPB has not been described previously. The
      NADH:ubiquinone oxidoreductase gene may have a role in the regulation of
      molecular changes during the global cardiac ischemia/reperfusion injury during
      CPB, such as the up-regulation of Bcl-2, which might block release of cytochrome
      c from the mitochondria and prevent cardiomyocytic apoptosis.

PMID- 14718446
TI  - Mechanical properties of tracheal smooth muscle are impaired in the rabbit with
      experimental cardiac pressure overload.
AB  - STUDY OBJECTIVES/DESIGN: Impaired function of striated and arterial smooth muscle
      is known to occur in humans and animals with various forms of cardiac diseases,
      but limited information is available on the mechanical behavior of airway smooth
      muscle. We tested the hypothesis that the baseline mechanical properties of
      tracheal smooth muscle (TSM) were impaired at an early stage of cardiac overload.
      ANIMALS: We used a model of cardiac hypertrophy induced by surgical abdominal
      aortic stenosis (AS) in adult rabbits. Twelve animals with AS and 8 sham-operated
      control rabbits were studied 12 weeks after surgery. In rabbits with AS, the
      heart weight/body weight ratio was higher than in control rabbits (2.36 +/- 0.43
      g/kg vs 1.98 +/- 0.20 g/kg, p < 0.05) [mean +/- SD], attesting to moderate
      cardiac hypertrophy. No clinical signs of congestive heart failure were observed.
      MEASUREMENTS: Isolated TSM strips were electrically stimulated at 37 degrees C,
      2.5 mM [Ca(2+)](0), against 8 to 10 load levels, from zero load to full isometry.
      Force-velocity relationship was elicited using the conventional afterloaded
      isotonic method. RESULTS: Peak isometric tension was lower in rabbits with AS
      than in control rabbits (25 +/- 11 mN/mm(2) vs 34 +/- 14 mN/mm(2), p < 0.05),
      whereas maximum unloaded shortening velocity, maximum extent of muscle
      shortening, and relaxation parameters did not differ between groups. The
      curvature of the force-velocity relationship (which reflects the myothermal
      economy of force generation) and peak mechanical efficiency were lower in rabbits
      with AS than in control rabbits. CONCLUSIONS: These results indicate that the
      contraction of isolated rabbit TSM was less powerful and less economical in
      cardiac hypertrophy, attesting to early impairment of the mechanical properties
      of TSM during cardiac overload.

PMID- 14718447
TI  - Effects of hyperchloremic acidosis on arterial pressure and circulating
      inflammatory molecules in experimental sepsis.
AB  - STUDY OBJECTIVE: To determine the effects of hyperchloremic acidosis, induced by
      dilute HCl infusion, on BP and circulating inflammatory mediators in an
      experimental model of severe sepsis in the rat. DESIGN: Randomized, open-label,
      controlled experiment. SETTING: University research laboratory. PARTICIPANTS:
      Twenty-four adult, male, Sprague-Dawley rats. INTERVENTION: Eighteen hours after
      inducing lethal sepsis by cecal ligation and puncture, animals were randomized
      and classified into three groups. In groups 2 and 3, we began an IV infusion of
      0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15
      mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer
      solution. In all groups, infusions were continued for 8 h or until the animals
      died. MEASUREMENTS: We measured mean arterial pressure (MAP), arterial blood
      gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, and IL-10 levels at 0 h, 3 h, 6 h, and 8 h. RESULTS: MAP
      remained stable in group 1 but decreased in groups 2 and 3 (p < 0.001), such that
      at 8 h MAP was much higher in group 1 (94 +/- 9.2 mm Hg) [+/- SD] compared to
      either group 2 (71.6 +/- 20.1 mm Hg) or group 3 (49.4 +/- 33.2 mm Hg) [p = 0.01].
      This change in MAP correlated with the increase in plasma Cl(-) (R(2) = 0.50, p <
      0.0001) and less well with the decrease in pH (R(2) = 0.24, p < 0.001). After 6 h
      of acidosis, plasma nitrite levels were significantly higher in group 2 animals
      compared to either group 1 or group 3 animals (p < 0.05). Plasma TNF-alpha, IL-6,
      or IL-10 levels were not significantly different from control animals.
      CONCLUSION: Moderate acidosis (SBE of 5 to 10 mEq/L), induced by HCl infusion,
      worsened BP and increased plasma nitrate/nitrite levels but had no effect on
      circulating cytokines in septic rats. However, severe acidosis (SBE of 10 to 15
      mEq/L), while still causing hypotension, did not affect plasma nitrate/nitrite
      levels.

PMID- 14718448
TI  - The role of long-acting bronchodilators in the management of stable COPD.
AB  - Bronchodilators form the foundation of symptomatic treatment of COPD. Several
      long-acting bronchodilators are now available for use in COPD, but publications
      of large-scale studies of their efficacy have, for the most part, postdated the
      publication of major clinical guidelines. This article provides a critical review
      of large (> or =50 patients), double-blind, clinical trials of three long-acting
      bronchodilators in COPD (the once-daily anticholinergic tiotropium, and the twice
      daily beta(2)-agonists formoterol and salmeterol) within the context of the
      objectives of treatment defined by the Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) guidelines. Fourteen published studies were identified, of
      which 12 studies were published since the release of the GOLD guidelines. All
      three long-acting bronchodilators were found to effectively improve lung
      function; however, they differed in their effects on outcomes other than
      bronchodilation, with salmeterol demonstrating inconsistent efficacy compared
      with placebo in preventing exacerbations and improving health status, and only
      tiotropium demonstrating consistent superiority to the short-acting
      bronchodilator ipratropium. Based on this review, a treatment algorithm for the
      introduction of long-acting bronchodilators to patients with COPD is proposed,
      which includes the use of long-acting bronchodilators early in the treatment
      algorithm.

PMID- 14718449
TI  - Pulmonary infiltrates in the non-HIV-infected immunocompromised patient:
      etiologies, diagnostic strategies, and outcomes.
AB  - Pulmonary complications remain a major cause of both morbidity and mortality in
      immunocompromised patients. When such individuals present with radiographic
      infiltrates, the clinician faces a diagnostic challenge. The differential
      diagnosis in this setting is broad and includes both infectious and noninfectious
      processes. Rarely are the radiographic findings classic for one disease, and most
      potential etiologies have overlapping clinical and radiographic appearances. In
      recent years, several themes have emerged in the literature on this topic. First,
      an aggressive approach to identifying a specific etiology is necessary; as a
      corollary, diagnostic delay increases the risk for mortality. Second, the
      evaluation of these infiltrates nearly always entails bronchoscopy. Bronchoscopy
      allows identification of some etiologies with certainty, and often allows for the
      exclusion of infectious agents even if the procedure is otherwise unrevealing.
      Third, early use of CT scanning regularly demonstrates lesions missed by plain
      radiography. Despite these advances, initial therapeutic interventions include
      the use of broad-spectrum antibiotics and other anti-infectives in order to
      ensure that the patients is receiving appropriate therapy. With the results of
      invasive testing, these treatments are then narrowed. Frustratingly, outcomes for
      immunocompromised patients with infiltrates remain poor.

PMID- 14718451
TI  - Timing of peak troponin T and creatine kinase-MB elevations after percutaneous
      coronary intervention.
AB  - STUDY OBJECTIVE: The prognostic significance of elevations in creatine kinase-MB
      and troponin T (cTnT), which have been conventionally measured 6 to 8 h after
      percutaneous coronary intervention (PCI), has been established. However, the time
      to peak biomarker appearance in the circulation has not been defined and is the
      purpose of this pilot study. DESIGN: Nonrandomized, nonconsecutive patient
      cohort. SETTING: Clinical practice, Mayo Clinic, Rochester, MN. PATIENTS: Cohort
      (n = 57) undergoing elective PCI. INTERVENTIONS: cTnT and creatine kinase (CK)-MB
      measured at baseline, 2 h, 4 h, 8 h, and > or = 2 h (mean +/- SEM, 18 +/- 5 h)
      after PCI. MEASUREMENTS AND RESULTS: Postprocedure cTnT elevations were detected
      in 30 of 57 patients (53%). Of these, 4 of 30 patients (13%) had peak cTnT at 4 h
      (0.80 +/- 0.40 ng/mL), 5 of 30 patients (17%) had peak cTnT at 8 h (1.07 +/- 0.48
      ng/mL), and 21 of 30 patients (70%) had peak cTnT at > or = 12 h (0.21 +/- 0.06
      ng/mL); 22 of 30 patients received abciximab. Elevations in CK-MB occurred in 14
      of 57 patients (25%). Of these, 3 of 14 patients (21%) demonstrated peak CK-MB at
      2 h (18.5 +/- 7.9 ng/mL) and the remainder (11 of 14 patients, 79%) during the 12
      to 20-h interval (20.2 +/- 4.4 ng/mL); 12 of 14 patients received abciximab.
      CONCLUSION: More cTnT than CK-MB elevations occur after PCI; however, both
      biomarkers demonstrate a longer time to peak value than anticipated in clinical
      practice. Early surveillance monitoring (< 12 h) does not detect peak biomarker
      levels, especially in patients with normal baseline values. If peak levels are to
      be used to determine prognosis, then longer time intervals should be used for
      post-PCI surveillance. The timing of peak elevations appears to be influenced by
      baselines values as well. Early elevations may reflect the conjoint effects of
      injury associated with the disease process and the intervention itself. These
      data suggest that a re-evaluation of surveillance monitoring to account for the
      variability reported and the influence of baseline elevations of biomarkers may
      improve the prognostic power of the measurements.

PMID- 14718452
TI  - Increased exhaled nitric oxide following autologous peripheral hematopoietic stem
      cell transplantation: a potential marker of idiopathic pneumonia syndrome.
AB  - BACKGROUND: Increased production of nitric oxide (NO) and oxidative stress
      following bone marrow transplantation may play a role in the pathogenesis of
      idiopathic pneumonia syndrome (IPS). We hypothesize that patients who received
      high-dose chemotherapy followed by autologous peripheral hematopoietic stem-cell
      transplantation (APHSCT) have increased exhaled NO. METHOD: We measured exhaled
      lower respiratory tract NO concentration with a chemiluminescent NO analyzer
      during a slow vital capacity maneuver against a positive pressure of 16 cm H(2)O
      at an expiratory flow rate of 50 mL/s in 20 female patients who received high
      dose chemotherapy (cyclophosphamide, carmustine, and cisplatin) followed by
      APHSCT for the treatment of stage III or IV breast carcinoma. Pulmonary function
      tests were performed, and exhaled NO measurements and clinical and laboratory
      data were obtained before transplantation and at every 6-week visit after
      transplantation for 24 weeks. RESULTS: All study patients had evidence of IPS
      with dyspnea and reduction in diffusion capacity of the lung for carbon monoxide
      (DLCO). Lower respiratory tract exhaled NO was significantly higher after APHSCT
      and during the 6 months of follow-up. Mean (+/- SD) exhaled NO increased from
      (mean +/- SD) 12.54 +/- 1.32 parts per billion (ppb) before APHSCT to 21.26 +/-
      1.94 ppb at 6 weeks (p = 0.099), 21.26 +/- 1.94 ppb (p = 0.006) at 12 weeks,
      24.62 +/- 2.55 ppb (p = 0.012) at 18 weeks, and 25.28 +/- 3.31 ppb (p = 0.013) at
      24 weeks (all p values were compared to baseline). There was a strong negative
      correlation between DLCO and exhaled NO (regression coefficient - 0.60, p =
      0.01). CONCLUSION: Lower respiratory tract concentration of exhaled NO is
      significantly increased following APHSCT and correlates with reduction in DLCO.
      Increase in lower respiratory tract concentration of NO is a potential marker of
      IPS.

PMID- 14718453
TI  - Can exogenously administered hyaluronan improve respiratory function in patients
      with pulmonary emphysema?
AB  - While most attempts at developing a treatment for pulmonary emphysema have
      focused on the use of elastase inhibitors to reduce elastic fiber damage and the
      loss of alveoli, this laboratory has developed a method of preventing such injury
      by the intratracheal administration of hyaluronan (HA). Animals treated with HA
      prior to the induction of experimental emphysema develop significantly less
      disease than untreated controls. The protective effect of HA may be related to
      its ability to bind to lung elastic fibers, thereby preventing their breakdown by
      elastases. Although clinical trials involving nebulized HA are not expected to
      yield a measurable treatment effect for at least several years, it is proposed
      that the special ability of this polysaccharide to retain water may increase the
      elasticity of lung elastic fibers, producing a relatively rapid improvement in
      pulmonary mechanics. Such an outcome might speed the development of this
      potential treatment for pulmonary emphysema.

PMID- 14718455
TI  - Chronotropic incompetence in a young adult: case report and literature review.
AB  - Chronotropic incompetence (CI) is the inability of heart rate response to meet
      metabolic demand. CI is associated with sinus node dysfunction, atrial
      fibrillation, or structural heart disease, and can lead to functional impairment.
      We report the case of a 34-year-old man with CI secondary to sinus node
      dysfunction who demonstrated significant improvement in functional capacity with
      rate-responsive pacing. Therapy for CI should be guided by the treatment of the
      underlying cause with consideration for rate-responsive pacing in symptomatic
      patients. The prognosis of CI is variable and dependent on underlying etiology.

PMID- 14718454
TI  - Making an impossible mission possible.
AB  - Cardiovascular disease (CVD) is widespread in developing countries. Hypertension
      is a major contributor of CVD. Left ventricular hypertrophy (LVH) is a risk
      marker in hypertensive populations. Identification of LVH and treatment of high
      risk patients can result in more effective use of the limited resources. LVH is
      diagnosed by echocardiography, often unavailable in developing countries. In
      Gambia, we used a hand-carried ultrasound (HCU) to examine 1,997 people.
      Seventeen percent had hypertension; of these, LVH was found in 65%. The battery
      powered HCU permits clinicians to detect LVH in areas with limited access to
      diagnostic equipment, allowing identification of a high-risk hypertensive
      population.

PMID- 14718456
TI  - Dysphagia after Heimlich maneuver.

PMID- 14718457
TI  - Woman with COPD and fixed and dilated pupil following head trauma.

PMID- 14718458
TI  - Bronchoscope reprocessing and infection prevention and control: bronchoscopy
      specific guidelines are needed.
AB  - BACKGROUND: It has been recommended that bronchoscopists familiarize themselves
      with national recommendations for bronchoscope reprocessing practices, but the
      extent of guideline awareness is unclear. METHODS: We distributed a survey to
      practicing bronchoscopists at two meetings. Questions addressed infection control
      issues related to bronchoscopy and specific reprocessing recommendations.
      RESULTS: A total of 46 surveys were completed by medical directors of
      bronchoscopy suites (26%) and attending bronchoscopists (74%) who had graduated
      from medical school a median of 22 years ago and performed a median of 19
      procedures per month. Sixty-five percent of respondents, including 55% of
      directors, were not familiar with national reprocessing recommendations, and 39%
      did not know the approach to reprocessing at their own institution. Respondents
      who did > 20 procedures per month trended toward being more likely to be aware of
      guidelines (54% vs 26%, p = 0.09) and were less likely to answer "do not know" to
      more than one question about specific reprocessing details (25% vs 70%, p =
      0.003). Seventy-eight percent of respondents did not know local practices for at
      least one of the reprocessing details. Forty-six percent of respondents stated
      their institutions followed recommendations that records be kept of the specific
      bronchoscope used in each case. CONCLUSIONS: Many experienced bronchoscopists are
      unfamiliar with national guidelines and local practices related to bronchoscope
      reprocessing. Publication of bronchoscope-specific, comprehensive reprocessing
      guidelines in the pulmonary literature may help increase familiarity with this
      crucial process.

PMID- 14718459
TI  - The efficacy of premixed nitrous oxide and oxygen for fiberoptic bronchoscopy in
      pediatric patients: a randomized, double-blind, controlled study.
AB  - STUDY OBJECTIVE: s: The aim of the study was to evaluate the efficacy and safety
      of premixed 50% nitrous oxide and oxygen on the quality of sedation and pain
      control during fiberoptic bronchoscopy (FB) in children. DESIGN: A prospective,
      randomized, double-blind study. SETTING: Pediatric pulmonary department in a
      pediatric tertiary university hospital. PATIENTS: One hundred five children aged
      1 month to 18 years. INTERVENTIONS: Patients inhaled after sedation and local
      anesthesia either premixed 50% nitrous oxide and oxygen (nitrous oxide group) or
      premixed 50% nitrogen and oxygen (control group) during FB. MEASUREMENT AND
      RESULTS: The rate of failure was significantly greater in the control group (62%)
      than in the nitrous oxide group (21%, p = 0.00003). The efficacy of premixed 50%
      nitrous oxide and oxygen was also demonstrated with higher satisfaction scores (p
      = 0.000001), lower Children's Hospital of Eastern Ontario Pain Scores (p =
      0.002), better visual analog scale ratings (p = 0.03), and improved behavior
      scores. Side effects were minor and similar in both groups. CONCLUSIONS: This
      study demonstrates the improved efficacy of sedation, pain control, and safety of
      premixed 50% nitrous oxide and oxygen for FB in children.

PMID- 14718460
TI  - Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration:
      a randomized trial.
AB  - STUDY OBJECTIVE: Our group performed a randomized trial to assess whether the
      addition of endobronchial ultrasound (EBUS) guidance will lead to better results
      than standard transbronchial needle aspiration (TBNS). EBUS guidance seems to be
      beneficial in increasing the yield of TBNA but has not been proven to be superior
      to conventional procedures in a randomized trial. METHODS: Consecutive patients
      who were referred for TBNA were randomized to an EBUS-guided and a conventional
      TBNA arm. Patients with subcarinal lymph nodes were randomized and analyzed
      separately (group A) from all other stations (group B). A positive result was
      defined as either lymphocytes or a specific abnormality on cytology. RESULTS: Two
      hundred patients were examined (100 patients each in groups A and B). Half of the
      patients underwent EBUS-guided TBNA rather than conventional TBNA. In group A,
      the yield of conventional TBNA was 74% compared to 86% in the EBUS group
      (difference not significant). In group B, the overall yields were 58% and 84%,
      respectively. This difference was statistically highly significant (p < 0.001).
      The average number of passes was four. CONCLUSION: EBUS guidance significantly
      increases the yield of TBNA in all stations except in the subcarinal region. It
      should be considered to be a routine adjunct to TBNA. On-site cytology may be
      unnecessary, and the number of necessary needle passes required is low.

PMID- 14718461
TI  - Decreased respiratory symptoms after intervention in artificially ventilated
      offices in Sao Paulo, Brazil.
AB  - BACKGROUND: The increase in work-related respiratory complaints in artificially
      ventilated buildings have multiple causes, and intervention studies are a
      valuable approach to understanding possible mechanisms. STUDY OBJECTIVES: To
      analyze the effects of an intervention in a ventilation system with > 20 years of
      continuous use, and with a high rate of building-related respiratory complains.
      DESIGN: An epidemiologic study was done among individuals working in places with
      ventilation machinery and ducts with > 20 years of use, before and after
      intervention. Analysis of symptoms and logistic regression were performed to
      check the associations between air-conditioning intervention and reported
      symptoms. RESULTS: The air-conditioning intervention showed a protective effect
      on building-related worsening of respiratory symptoms (odds ratio, 0.132; 95%
      confidence interval, 0.030 to 0.575), naso-ocular symptoms (odds ratio, 0.231;
      95% confidence interval, 0.058 to 0.915), and persistent cough (odds ratio,
      0.071; 95% confidence interval, 0.014 to 0.356). CONCLUSION: Intervention in high
      risk occupational locations can be effective in improving perceived indoor air
      quality.

PMID- 14718462
TI  - A 19-year-old man with nonresolving pneumonia.

PMID- 14718463
TI  - Obstructive sleep apnea syndrome complicating oculopharyngeal muscular dystrophy.
AB  - We report a 75-year-old Spanish-American woman who received a diagnosis of
      oculopharyngeal muscular dystrophy after presenting with ptosis and dysphagia.
      She also complained of snoring and daytime somnolence, and was found to have
      obstructive sleep apnea (OSA) syndrome attributable to her neuromuscular
      disorder. This is the first report of OSA syndrome complicating typical, adult
      onset oculopharyngeal muscular dystrophy, and should prompt the evaluation of
      other such patients for sleep-disordered breathing.

PMID- 14718464
TI  - Chyloptysis in adults: presentation, recognition, and differential diagnosis.
AB  - Chyloptysis is a rare finding, and the accompanying respiratory symptoms are
      usually nonspecific. The recognition of the chylous nature of the sputum is
      requisite for proper diagnosis, especially if chyloptysis is not accompanied by
      chylous pleural effusion. The key to the differential diagnosis of chyloptysis is
      to consider illnesses that can induce reflux of chyle into the bronchial tree.
      There are two mechanisms postulated: the first requires the presence of an
      abnormal communication between the bronchial tree and the lymphatic channels, and
      the second requires a bronchopleural fistula in the context of a chylous pleural
      effusion. Chyloptysis in adults should prompt assessment for evidence of
      lymphatic obstruction from trauma, radiation, and malignancy, and to exclude
      diseases with known association with chyloptysis, ie, lymphangioleiomyomatosis,
      yellow nail syndrome, or thoracic lymphangiectasis. A lymphangiogram is
      recommended to define the abnormality. In the case of lymphangiectasis, patients
      respond to either dietary modification and/or ligation of the thoracic duct.

PMID- 14718465
TI  - Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after
      stereotactic radiotherapy for lung tumors.
AB  - To determine the usefulness of serum KL-6 levels for predicting the occurrence of
      radiation pneumonitis (RP) after the application of single high-dose stereotactic
      radiation therapy for lung tumors, the serum KL-6 levels were measured in 16
      patients before irradiation and every 1 or 2 months thereafter. Three of the 16
      patients experienced RP of grade 3 severity according to the European
      Organization for Research and Treatment of Cancer/Radiation Therapy Oncology
      Group toxicity criteria. RP occurred 3 months after the completion of radiation
      therapy in two patients, and 4 months after completion in one patient. RP
      occurred at significantly increased frequencies in patients with primary lung
      cancer (p = 0.01) and adenocarcinoma (p = 0.01), and in those undergoing the
      concurrent irinotecan therapy (p = 0.02). In all 16 patients, the lactate
      dehydrogenase level remained normal during the follow-up period. In all three of
      the patients with RP, KL-6 levels increased by > 1.5-fold compared to the
      pretreatment value and over the cutoff level of 500 IU. The ratio of the increase
      in serum KL-6 values 2 months after the patient had undergone irradiation showed
      a significant correlation with the occurrence of RP (p = 0.04). In conclusion, KL
      6 is a useful marker for prediction of the occurrence of RP after single,
      fractional, high-dose stereotactic irradiation of lung tumors.

PMID- 14718466
TI  - Reversal of nocturnal periodic breathing in primary pulmonary hypertension after
      lung transplantation.
AB  - Nocturnal periodic breathing (PB) closely resembling Cheyne-Stokes respiration in
      congestive heart failure has been reported to occur in end-stage primary
      pulmonary hypertension (PPH). We herein describe the clinical course of a 56-year
      old female patient with PPH and severe hypoxemia, hypocapnia, and right
      ventricular compromise in whom sleep-disordered breathing (SDB) resolved after
      successful double-lung transplantation. This case illustrates the crucial roles
      of blood gas alterations and hemodynamic impairment in the emergence of PB in
      PPH, and is in favor of a genuine association between advanced right heart
      failure and the development of SDB.

PMID- 14718467
TI  - Tianeptine: a new exploratory therapy for asthma.

PMID- 14718468
TI  - Diffuse aspiration bronchiolitis due to achalasia.

PMID- 14718469
TI  - Lung cancer screening: response to Jerome Reich, MD.

PMID- 14718471
TI  - Obesity-hypoventilation syndrome: the name game continues.

PMID- 14718472
TI  - Evaluating combination therapy in community-acquired pneumonia.

PMID- 14718473
TI  - Bird-years as well as pack-years.

PMID- 14718474
TI  - Mycobacteria in pathogenesis of sarcoidosis.

PMID- 14718475
TI  - Balloon dilatation using flexible bronchoscopy for the management of benign and
      malignant airway stenoses.

PMID- 14718478
TI  - Ionic currents mediated by a prokaryotic homologue of CLC Cl- channels.
AB  - CLC-ec1 is an E. coli homologue of the CLC family of Cl- channels, which are
      widespread throughout eukaryotic organisms. The structure of this membrane
      protein is known, and its physiological role has been described, but our
      knowledge of its functional characteristics is severely limited by the absence of
      electrophysiological recordings. High-density reconstitution and incorporation of
      crystallization-quality CLC-ec1 in planar lipid bilayers failed to yield
      measurable CLC-ec1 currents due to porin contamination. A procedure developed to
      prepare the protein at a very high level of purity allowed us to measure
      macroscopic CLC-ec1 currents in lipid bilayers. The current is Cl- selective, and
      its pH dependence mimics that observed with a 36Cl- flux assay in reconstituted
      liposomes. The unitary conductance is estimated to be <0.2 pS. Surprisingly, the
      currents have a subnernstian reversal potential in a KCl gradient, indicating
      imperfect selectivity for anions over cations. Mutation of a conserved glutamate
      residue found in the selectivity filter eliminates the pH-dependence of both
      currents and 36Cl- flux and appears to trap CLC-ec1 in a constitutively active
      state. These effects correlate well with known characteristics of eukaryotic CLC
      channels. The E148A mutant displays nearly ideal Cl- selectivity.

PMID- 14718479
TI  - A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells
      from rat mesenteric resistance arteries.
AB  - We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent
      calcium-activated inward current in vascular smooth-muscle cells, and suggested
      this to be of importance in synchronizing smooth-muscle contraction. Here we
      demonstrate the characteristics of this current. Using conventional patch-clamp
      technique, whole-cell currents were evoked in freshly isolated smooth-muscle
      cells from rat mesenteric resistance arteries by elevation of intracellular
      calcium with either 10 mM caffeine, 1 microM BAY K8644, 0.4 microM ionomycin, or
      by high calcium concentration (900 nM) in the pipette solution. The current was
      found to be a calcium-activated chloride current with an absolute requirement for
      cyclic GMP (EC50 6.4 microM). The current could be activated by the
      constitutively active subunit of PKG. Current activation was blocked by the
      protein kinase G antagonist Rp-8-Br-PET-cGMP or with a peptide inhibitor of PKG,
      or with the nonhydrolysable ATP analogue AMP-PNP. Under biionic conditions, the
      anion permeability sequence of the channel was SCN- > Br- > I- > Cl- > acetate >
      F- >> aspartate, but the conductance sequence was I- > Br- > Cl- > acetate > F- >
      aspartate = SCN-. The current had no voltage or time dependence. It was inhibited
      by nickel and zinc ions in the micromolar range, but was unaffected by cobalt and
      had a low sensitivity to inhibition by the chloride channel blockers niflumic
      acid, DIDS, and IAA-94. The properties of this current in mesenteric artery
      smooth-muscle cells differed from those of the calcium-activated chloride current
      in pulmonary myocytes, which was cGMP-independent, exhibited a high sensitivity
      to inhibition by niflumic acid, was unaffected by zinc ions, and showed outward
      current rectification as has previously been reported for this current. Under
      conditions of high calcium in the patch-pipette solution, a current similar to
      the latter could be identified also in the mesenteric artery smooth-muscle cells.
      We conclude that smooth-muscle cells from rat mesenteric resistance arteries have
      a novel cGMP-dependent calcium-activated chloride current, which is activated by
      intracellular calcium release and which has characteristics distinct from other
      calcium-activated chloride currents.

PMID- 14718480
TI  - Sex differences in the effect of dietary restriction on life span and mortality
      rates in female and male Drosophila melanogaster.
AB  - Dietary restriction (DR) has been shown to increase life span in taxonomically
      diverse animal species. In this study we tested for sex differences in the
      response of life span to graded severity of DR in Drosophila melanogaster. In
      both sexes, life span peaked at an intermediate food concentration and declined
      on either side. However, the magnitude of the response and the food concentration
      that minimized adult mortality differed significantly between the sexes. Female
      life span peaked at a food concentration 60% of the standard laboratory diet
      compared to a concentration of 40% for males. Moreover, female flies subject to
      DR lived up to 60% longer than did starved or fully fed females, whereas males
      subjected to DR lived only up to 30% longer. Analysis of age-specific mortality
      rates showed that DR extended life span by decreasing baseline mortality rates in
      both sexes, and to a greater extent in females. The differences in the response
      to DR in female and male Drosophila may be due to previously documented sex
      differences in sensitivity of life span to insulin/insulin-like growth factor-1
      signalling or in nutrient/energy demand and allocation/utilization.

PMID- 14718481
TI  - Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in
      elderly men.
AB  - We investigated the association of vitamin D receptor (VDR) genotype with fat
      free mass (FFM) in a cohort of 302 older (aged 58-93 years) Caucasian men who
      underwent body composition analysis by dual-energy X-ray absorptiometry, and
      completed questionnaires addressing comorbidities, physical activity, and dietary
      intake. All participants were genotyped for a VDR translation start site (FokI)
      polymorphism [FF (37.7%), Ff (48.4%), and ff (13.9%)] and the previously studied
      BsmI polymorphism [BB (24.9%), Bb (37.7%), and bb (37.4%)]. The BsmI polymorphism
      was not associated with FFM in any analysis; however, the FokI polymorphism was
      significantly associated with total FFM, appendicular FFM, and relative (kg/m(2))
      appendicular FFM (all p <.05), with the FF group demonstrating significantly
      lower FFM than the Ff and ff groups (e.g., total FFM: FF = 57.6 +/- 0.4, Ff =
      59.4 +/- 0.4, ff = 59.4 +/- 0.7 kg; p <.02). Age-adjusted logistic regression
      revealed a 2.17-fold higher risk for sarcopenia (defined previously as
      appendicular FFM <7.26 kg/m(2)) in FF homozygotes (95% CI [confidence interval] =
      1.19-3.85; p =.03) compared to men with one or more f alleles. The VDR
      translation start site (FokI) polymorphism is significantly associated with FFM
      and sarcopenia in this cohort of older Caucasian men.

PMID- 14718482
TI  - The APOE gene and differences in life expectancy in Europe.
AB  - Common alleles of the apolipoprotein-E gene (APOE) are associated with different
      risks of ischemic heart disease, Alzheimer's disease, and other chronic
      conditions in European populations. Also, the APOE allele frequencies vary widely
      among European countries. We estimated the proportion of differences in mortality
      and differences in life span that are attributable to differences in APOE allele
      frequencies in Europe. Mortality rates by age, sex, and APOE genotype for six
      countries (Denmark, Finland, France, Italy, the Netherlands, and Sweden) were
      used to standardize mortality rates to the allele frequencies in Italy.
      Differences in APOE allele frequencies explain 12%-17% of the variation among
      these countries in mortality in people older than 65 years and 1%-2% of the
      variation in life span in those older than 65 years. Differences by genotype in
      mortality in people older than 15 years account for about 3.5% of the genetic
      contribution to the variation in life span in Denmark.

PMID- 14718483
TI  - The top 10 hot topics in aging.

PMID- 14718484
TI  - The management of venous thromboembolic disease in older adults.
AB  - The incidence and prevalence of venous thromboembolic disease (VTED) increase
      progressively with age. Although the clinical features, diagnosis, and treatment
      of VTED are generally similar in older and younger adults, prevalent
      comorbidities often complicate the management of VTED in the elderly. The Sixth
      American College of Chest Physicians Consensus Conference on Antithrombotic
      Therapy provides comprehensive recommendations for the management of VTED. This
      article summarizes these recommendations as they apply to older adults and
      highlights factors that may modulate the diagnosis and treatment of VTED in the
      elderly patient.

PMID- 14718485
TI  - The prevention of venous thromboembolism in older adults: guidelines.
AB  - The rationale for thromboprophylaxis is based on the high prevalence of venous
      thromboembolism (VTE), a disorder involving deep vein thrombosis (DVT) and
      pulmonary embolism (PE), among hospitalized patients, the clinically silent
      nature of VTE in most patients, and the morbidity, cost, and potential mortality
      associated with unprevented thromboembolism. Both DVT and PE cause few specific
      symptoms, and the clinical diagnosis is unreliable. Since the first clinical
      manifestation of VTE may be fatal PE, it is inappropriate to wait for symptoms
      before treatment. Unrecognized and untreated DVT may also cause the postphlebitic
      syndrome and predispose patients to subsequent episodes of recurrent VTE. Routine
      screening for VTE has also not been shown to reduce the incidence of symptomatic
      VTE or fatal PE. Use of effective methods of prophylaxis is more cost effective
      and is safer than selective, intensive screening for VTE. This article reviews
      current recommendations for the prevention of VTE as they apply to older adults.
      The recommendations discussed are based on the Sixth American College of Chest
      Physicians Consensus Conference on Antithrombotic Therapy reported in Chest.
      2001;119:132S-175S.

PMID- 14718486
TI  - Systematic review of progressive resistance strength training in older adults.
AB  - BACKGROUND: The aim of this systematic review was to quantify the effectiveness
      of progressive resistance strength training (PRT) to reduce physical disability
      in older people. METHODS: Randomized controlled trials were identified from
      searches of relevant databases and study reference lists and contacts with
      researchers. Two reviewers independently screened the trials for eligibility,
      rated their quality, and extracted data. Only randomized controlled trials
      utilizing PRT as the primary intervention in participants, whose group mean age
      was 60 years or older, were included. Data were pooled using fixed or random
      effect models to produce weighted mean differences (WMD) and 95% confidence
      intervals (CI). Standardized mean differences (SMD) were calculated when
      different units of measurement were used for the outcome of interest. RESULTS: 62
      trials (n = 3674) compared PRT with a control group. 14 trials had data available
      to allow pooling of disability outcomes. Most trials were of poor quality. PRT
      showed a strong positive effect on strength, although there was significant
      heterogeneity (41 trials [n = 1955], SMD 0.68; 95% confidence interval [CI] 0.52,
      0.84). A modest effect was found on some measures of functional limitations such
      as gait speed (14 trials [n = 798], WMD 0.07 meters per second; 95% CI 0.04,
      0.09). No evidence of an effect was found for physical disability (10 trials [n =
      722], SMD 0.01; 95% CI -0.14, 0.16). Adverse events were poorly investigated, but
      occurred in most studies where they were defined and prospectively monitored.
      CONCLUSIONS: PRT results in improvements to muscle strength and some aspects of
      functional limitation, such as gait speed, in older adults. However, based on
      current data, the effect of PRT on physical disability remains unclear. Further,
      due to the poor reporting of adverse events in trials, it is difficult to
      evaluate the risks associated with PRT.

PMID- 14718487
TI  - Long-term effects of lipoprotein(a) on carotid atherosclerosis in elderly
      Japanese.
AB  - BACKGROUND: Serum level of lipoprotein(a) [Lp(a)] is hereditarily constant
      throughout life within an individual, but the relationship between Lp(a) and
      atherosclerosis in elderly people is still controversial. METHODS: Serum Lp(a)
      levels were studied in 208 elderly Japanese participants aged 80 years with a
      variety of diseases, using carotid ultrasonography (US), brain computerized
      tomography (CT), electrocardiography (ECG), and ankle brachial pressure index
      (ABPI). Carotid plaque lesions were divided into 3 types based on the US
      echogenicity assessed by a computer-assisted system: L type (hypoechoic plaque),
      H type (hyperechoic plaque), and M type (heterogeneous plaque). RESULTS: The
      frequency of the L type and occlusion was significantly higher in the high Lp(a)
      group (n = 38) than in the normal Lp(a) group (n = 170). The mean height of the
      plaque was also greater in the high Lp(a) group than in the normal Lp(a) group.
      There was no difference in CT findings between the two groups. Myocardial
      ischemia on ECG and low ABPI (<0.9) were both frequently, but not significantly,
      seen in the high Lp(a) group. Among factors influencing US findings, multiple
      regression analysis showed that high Lp(a) correlated markedly to L type and
      cigarette smoking correlated to M type. CONCLUSIONS: These findings indicate
      that, in Japanese elderly patients aged 80, serum Lp(a) strongly correlates with
      hypoechoic carotid lesions, which correspond histologically to lipid-rich,
      unstable atherosclerosis. This suggested that Lp(a) could promote the formation
      of atherosclerosis throughout life, and play a role as an independent risk factor
      for circulatory disturbance of the organ later in life.

PMID- 14718488
TI  - Nutritional risk predicts quality of life in elderly community-living Canadians.
AB  - BACKGROUND: Although nutrition parameters have been linked to quality of life
      (QOL), few studies have determined if nutritional risk predicts changes in QOL
      over time in older adults. METHODS: 367 frail older adults were recruited from 23
      service agencies in the community. Baseline interview included nutritional risk
      as measured by SCREEN (Seniors in the Community: Risk Evaluation for Eating and
      Nutrition), as well as a wide variety of covariates. Participants were contacted
      every 3 months for 18 months to determine QOL as measured by three questions from
      the Behavioral Risk Factor Surveillance System (BRFSS), a general whole-life
      satisfaction question, and a general change in QOL question. "Good physical
      health days" from the BRFSS was the focus of bivariate and multivariate analyses,
      adjusting for influential covariates. RESULTS: Seniors with high nutritional risk
      had fewer good physical health days and whole-life satisfaction at each follow-up
      point compared with those at low risk. In general, participants reported
      decreases in general QOL from baseline, with those in the moderate nutritional
      risk category most likely to report this change. Nutritional risk predicted
      change in good physical health days over time. Other important covariates
      include: gender, number of health conditions, perceived health, and age.
      CONCLUSIONS: Nutritional risk is an independent predictor of change in health
      related QOL. The results also indicate a relationship between nutrition and the
      more holistic view of QOL. Evaluation studies of interventions for older adults
      need to include QOL measures as potential outcomes to further demonstrate the
      benefits of good nutrition.

PMID- 14718489
TI  - Effects of testosterone on behavior, depression, and cognitive function in older
      men with mild cognitive loss.
AB  - BACKGROUND: The role of sex hormones in the prevention of cognitive decline is
      uncertain. Animal studies suggest mechanisms for sex hormones including
      testosterone to maintain optimal cognitive function. But, there are studies to
      suggest that endogenous testosterone levels are associated with aggression in men
      with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/-
      5 years, range 73-87 years) with early cognitive decline and bioavailable
      testosterone levels below 128 ng/dl (lower limit for adult normal range) were
      randomized to receive intramuscular testosterone (200 mg every 3 weeks) or
      placebo for 12 weeks. Outcome measures included sex hormones (testosterone,
      bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone),
      Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression
      Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency,
      Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks,
      and 10 weeks. RESULTS: All men completed the study. Total and bioavailable
      testosterone, estrone, and estradiol levels increased in men receiving
      testosterone, but no changes were detected in men receiving placebo. No
      significant changes were found in behavior following testosterone
      supplementation, nor was there evidence of change in depression or activities of
      daily living. No discernable changes were found in any of the cognitive tests.
      Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 +
      5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups,
      and prostate-specific antigen levels did not change significantly. CONCLUSION: No
      significant changes in behavior, function, depression, or cognitive performance
      occurred following 12 weeks of testosterone replacement in men with low
      testosterone levels and early-to-moderate cognitive impairment. This pilot work
      suggests that testosterone can be given to men with early cognitive impairment
      without significant concern about worsening aggressive or unwanted behaviors.

PMID- 14718490
TI  - Stability and sensitivity of nursing home quality indicators.

PMID- 14718491
TI  - Is an entertainment robot useful in the care of elderly people with severe
      dementia?
AB  - OBJECTIVE: An entertainment robot was used as occupational therapy instead of
      animal-assisted therapy to avoid any danger or injury to the patient and maintain
      cleanliness. This study compared the effectiveness of a robot animal, AIBO, with
      a toy. METHOD: AIBO is made of metal and responds to spoken commands. We
      demonstrated AIBO to severely demented elderly people living in a geriatric home
      and observed their reactions. RESULTS: The most frequent reactions to AIBO
      consisted of looking at, communicating with, and caring for AIBO. The patients
      recognized that AIBO was a robot. However, once we dressed AIBO, the patients
      perceived AIBO as either a dog or a baby. Nevertheless, the presentation of AIBO
      resulted in positive outcomes for the severe dementia patients, including
      increased communication between the patients and AIBO. CONCLUSION: AIBO was
      clearly an effective rehabilitation tool in the treatment of severely demented
      patients.

PMID- 14718492
TI  - Advancing the taxonomy of disability in older adults.
AB  - BACKGROUND: Refinement of the traditional task-based classification of disability
      is needed to advance the field of disability research and to inform clinical
      practice. We propose an enhancement of the taxonomy of disability that
      incorporates information about symptoms and impairments that directly contribute
      to disability. In the first step of this new development, we present evidence to
      support five categories of disability related to pain, balance, weakness,
      endurance, and other symptoms. METHODS: The Women's Health and Aging Study, begun
      in 1992, was a population-based study of older disabled women living in the
      Eastern region of Baltimore and surrounds. In-home examinations were conducted
      every 6 months for 3 years. During the second examination, the 879 participants
      were asked the main symptom cause of their disability for each activity with
      which they had difficulty. Symptom causes of disability in activities of daily
      living were grouped into five nonmutually exclusive categories as stated above.
      Descriptive analyses were used to compare groups according to sociodemographic,
      health, disease, and physical performance information. RESULTS: Women with pain
      related disability were younger, more obese, and had high prevalence of
      widespread pain and symptomatic osteoarthritis. Balance-related disability was
      related to having an age of 85 years or older, being Caucasian, and poor
      performance in tests of standing balance and gait. Women with weakness-related
      disability were older, more often African American and sedentary, had high
      prevalence of stroke and diabetes, and performed poorly in chair-stands and knee
      strength tests. Endurance-related disability was associated with low self-rated
      energy, depressive symptoms, smoking history, and lung and cardiovascular
      diseases. CONCLUSIONS: The proposed refinement of the taxonomy of disability
      describes a set of empirically derived symptom and impairment-related disability
      groupings that have criterion and face validity. Further research about symptom
      and impairment-related disability in other populations of older persons is
      warranted.

PMID- 14718493
TI  - High tech and high touch.

PMID- 14718494
TI  - Improving crop salt tolerance.
AB  - Salinity is an ever-present threat to crop yields, especially in countries where
      irrigation is an essential aid to agriculture. Although the tolerance of saline
      conditions by plants is variable, crop species are generally intolerant of one
      third of the concentration of salts found in seawater. Attempts to improve the
      salt tolerance of crops through conventional breeding programmes have met with
      very limited success, due to the complexity of the trait: salt tolerance is
      complex genetically and physiologically. Tolerance often shows the
      characteristics of a multigenic trait, with quantitative trait loci (QTLs)
      associated with tolerance identified in barley, citrus, rice, and tomato and with
      ion transport under saline conditions in barley, citrus and rice. Physiologically
      salt tolerance is also complex, with halophytes and less tolerant plants showing
      a wide range of adaptations. Attempts to enhance tolerance have involved
      conventional breeding programmes, the use of in vitro selection, pooling
      physiological traits, interspecific hybridization, using halophytes as
      alternative crops, the use of marker-aided selection, and the use of transgenic
      plants. It is surprising that, in spite of the complexity of salt tolerance,
      there are commonly claims in the literature that the transfer of a single or a
      few genes can increase the tolerance of plants to saline conditions. Evaluation
      of such claims reveals that, of the 68 papers produced between 1993 and early
      2003, only 19 report quantitative estimates of plant growth. Of these, four
      papers contain quantitative data on the response of transformants and wild-type
      of six species without and with salinity applied in an appropriate manner. About
      half of all the papers report data on experiments conducted under conditions
      where there is little or no transpiration: such experiments may provide insights
      into components of tolerance, but are not grounds for claims of enhanced
      tolerance at the whole plant level. Whether enhanced tolerance, where properly
      established, is due to the chance alteration of a factor that is limiting in a
      complex chain or an effect on signalling remains to be elucidated. After ten
      years of research using transgenic plants to alter salt tolerance, the value of
      this approach has yet to be established in the field.

PMID- 14718495
TI  - The transcriptional control of plant responses to phosphate limitation.
AB  - Plants have evolved an array of responses that adapt their growth to conditions
      of limited phosphate (Pi) supply. These involve biochemical and developmental
      changes that improve Pi acquisition and recycling, and protect against the stress
      of Pi starvation. The induction of these responses requires a sophisticated
      regulatory system that integrates information on external and internal plant Pi
      status and the details of this regulatory system are only just beginning to be
      elucidated. In this review, the current knowledge of this regulatory system is
      summarized, the hallmark of which is the central role of transcription factor
      PHR1 in the co-ordinated regulation of many phosphate-starvation-responsive
      genes. The role of hormonal signalling is also described, including auxins,
      ethylene and, particularly, cytokinins in the regulation of Pi-starvation
      responses.

PMID- 14718496
TI  - Response to water deficit and high temperature of transgenic peas (Pisum sativum
      L.) containing a seed-specific alpha-amylase inhibitor and the subsequent effects
      on pea weevil (Bruchus pisorum L.) survival.
AB  - The effects of water deficit and high temperature on the production of alpha
      amylase inhibitor 1 (alpha-AI-1) were studied in transgenic peas (Pisum sativum
      L.) that were developed to control the seed-feeding pea weevil (Bruchus pisorum
      L., Coleoptera: Bruchidae). Transgenic and non-transgenic plants were subjected
      to water-deficit and high-temperature treatments under controlled conditions in
      the glasshouse and growth cabinet, beginning 1 week after the first pods were
      formed. In the water-deficit treatments, the peas were either adequately watered
      (control) or water was withheld after first pod formation. The high-temperature
      experiments were performed in two growth cabinets, one maintained at 27/22
      degrees C (control) and one at 32/27 degrees C day/night temperatures, with the
      vapour pressure deficit maintained at 1.3 kPa. The plants exposure to high
      temperatures and water deficit produced 27% and 79% fewer seeds, respectively,
      than the controls. In the transgenic peas the level of alpha-AI-1 as a percentage
      of total protein was not influenced by water stress, but was reduced on average
      by 36.3% (the range in two experiments was 11-50%) in the high-temperature
      treatment. Transgenic and non-transgenic pods of plants grown at 27/22 degrees C
      and 32/27 degrees C were inoculated with pea weevil eggs to evaluate whether the
      reduction in level of alpha-AI-1 in the transgenic pea seeds affected pea weevil
      development and survival. At the higher temperatures, 39% of adult pea weevil
      emerged, compared to 1.2% in the transgenic peas grown at the lower temperatures,
      indicating that high temperature reduced the protective capacity of the
      transgenic peas.

PMID- 14718497
TI  - A novel cDNA from Parthenium argentatum Gray enhances the rubber biosynthetic
      activity in vitro.
AB  - Natural rubber (cis-1,4-polyisoprene) is an isoprenoid compound produced
      exclusively in plants by the action of rubber transferase. Despite a keen
      interest in revealing the mechanisms of rubber chain elongation and chain length
      determination, the molecular nature of rubber transferase has not yet been
      identified. A recent report has revealed that a 24 kDa protein tightly associated
      with the small rubber particles of Hevea brasiliensis, therefore designated small
      rubber particle protein (SRPP), plays a positive role in rubber biosynthesis.
      Since guayule (Parthenium argentatum Gray) produces natural rubber similar in
      size to H. brasiliensis, it is of critical interest to investigate whether
      guayule contains a similar protein to the SRPP. A cDNA clone has been isolated in
      guayule that shares a sequence homology with the SRPP, thus designated guayule
      homologue of SRPP (GHS), and the catalytic function of the protein was
      characterized. Sequence analysis revealed that the GHS is highly homologous in
      several conserved regions to the SRPP (50% identity). In vitro functional
      analysis of the recombinant protein overexpressed in E. coli revealed that the
      GHS plays a positive role in isopentenyl diphosphate incorporation into high
      molecular weight rubbers as SRPP does. These results indicate that guayule and
      Hevea rubber trees contain a protein that is similar in its amino acid sequence
      and plays a role in isopentenyl diphosphate incorporation in vitro, implying that
      it contributes to the enhancement of rubber biosynthetic activity in rubber
      trees.

PMID- 14718498
TI  - Isolation and location of three homoeologous dihydroflavonol-4-reductase (DFR)
      genes of wheat and their tissue-dependent expression.
AB  - DFR is involved in an important step in the flavonoid biosynthesis pathway
      upstream of anthocyanin, proanthocyanidin, and phlobaphene production, which
      contributes to the pigmentation of various plant tissues. Full genomic sequences
      of three DFRs were isolated in hexaploid wheat. Loci of TaDFRs were found in a
      more proximal region of the long arm of chromosomes of homoeologous group 3 than
      the R gene for red grain colour of wheat. These DFRs were designated TaDFR-A,
      TaDFR-B, and TaDFR-D on chromosome 3A, 3B, and 3D, respectively. In the 5'
      upstream region of DFR genes, two or three combinations of a G box core element
      and a putative binding site for a Myb-type transcription factor, P, of maize were
      found. Expression of DFR reached a maximal level in red grain of wheat cv.
      Chinese Spring (CS) at 5 d post-anthesis (DPA) and decreased gradually in the
      grain coat tissue from 10 to 20 DPA, in contrast to a very low expression level
      of DFR in white wheat grain during the same period. These DFRs differed in their
      expression. TaDFR-B and -D were expressed predominantly in grains. In developing
      leaves, DFR expression was light-responsive, and TaDFR-B was more up-regulated in
      leaves and roots than the other two.

PMID- 14718500
TI  - Electrogenic proton-regulated oxalate/chloride exchange by lobster
      hepatopancreatic brush-border membrane vesicles.
AB  - The transport of [14C]oxalate (Ox2-) by epithelial brush-border membrane vesicles
      (BBMV) of lobster (Homarus americanus) hepatopancreas, formed by a magnesium
      precipitation technique, was stimulated by an outward Cl- gradient (in > out). By
      contrast, Ox2- uptake was not enhanced by an inward Na+ or K+ transmembrane
      gradient. Generation of an inside-positive membrane potential by K+ in the
      presence of valinomycin stimulated Ox2-/Cl- exchange, while an inside-negative
      membrane potential generated by K+ efflux in the presence of valinomycin
      inhibited this process. Neither Ox2-/Ox2- nor Ox2-/SO4(2-) transport exchange
      were affected by alterations of transmembrane potential. An inwardly directed
      proton gradient, or the presence of low bilateral pH, enhanced Ox2-/Cl- exchange,
      yet the H+ gradient alone could not stimulate Ox2) uptake in Cl(-)-equilibrated
      BBMV or in vesicles lacking internal Cl-. The stilbenes 4-acetamido-4'
      isothiocyanotostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyano-2,2'
      disulfonic stilbene (DIDS) strongly inhibited Ox2-/Cl- exchange. Oxalate influx
      occurred by a combination of carrier-mediated transfer, exhibiting Michaelis
      Menten kinetics, and nonsaturable 'apparent diffusion'. Apparent kinetic
      constants for Ox2-/Cl- exchange were Kt = 0.20 mmol l(-1) and Jmax = 1.03 nmol l(
      1) mg(-1) protein 7 s(-1). 36Cl- influx into oxalate-loaded BBMV was stimulated
      by an inside-negative transmembrane potential compared with short-circuited
      vesicles. These results suggest that Ox2-/Cl- exchange in crustacean
      hepatopancreatic BBMV occurred by an electrogenic carrier mechanism exhibiting a
      1:1 flux ratio that was modulated by an external proton-sensitive regulatory
      site.

PMID- 14718501
TI  - The thermogenesis of digestion in rattlesnakes.
AB  - Some snakes have a feeding regime characterized by the infrequent ingestion of
      relatively large meals, causing impressive increments in post-prandial
      metabolism. Metabolism remains elevated for many days, while digestion proceeds,
      resulting in considerable investment of time and energy. Snakes actively adjust
      thermoregulatory behavior to raise their body temperature during digestion,
      exhibiting a post-prandial thermophilic response that accelerates digestion at
      the expense of higher metabolic rates. In the present study, we investigated the
      possibility that endogenously derived heat, originating as a byproduct of the
      post-prandial increase in metabolism, could itself contribute to the elevated
      body temperature during digestion in the South American rattlesnake Crotalus
      durissus. We assessed heat production, at a constant environmental temperature,
      by taking infrared (IR) images of snakes during fasting and after being fed meals
      varying from 10% to 50% of their own body masses. Our results show clearly that
      digesting rattlesnakes have significantly increased body temperatures, even when
      precluded from adjusting their thermoregulatory behavior. The feeding-derived
      thermogenesis caused the surface body temperature of rattlesnakes to increase by
      0.9-1.2 degrees C, a temperature change that will significantly affect digestive
      performance. The alterations in body temperature following feeding correlated
      closely with the temporal profile of changes in post-prandial metabolism.
      Moreover, the magnitude of the thermogenesis was greater for snakes fed large
      meals, as was the corresponding metabolic response. Since IR imaging only
      assesses surface temperatures, the magnitude of the thermogenesis and the changes
      in deep core temperature could be even more pronounced than is reported here.

PMID- 14718502
TI  - Mechanical work and muscular efficiency in walking children.
AB  - The effect of age and body size on the total mechanical work done during walking
      is studied in children of 3-12 years of age and in adults. The total mechanical
      work per stride (W tot) is measured as the sum of the external work, W ext (i.e.
      the work required to move the centre of mass of the body relative to the
      surroundings), and the internal work, W int (i.e. the work required to move the
      limbs relative to the centre of mass of the body, W int,k, and the work done by
      one leg against the other during the double contact period, W int,dc). Above 0.5
      m s(-1), both W ext) and W int,k, normalised to body mass and per unit distance
      (J kg(-1) m(-1)), are greater in children than in adults; these differences are
      greater the higher the speed and the younger the subject. Both in children and in
      adults, the normalised W int,dc shows an inverted U-shape curve as a function of
      speed, attaining a maximum value independent of age but occurring at higher
      speeds in older subjects. A higher metabolic energy input (J kg(-1) m(-1)) is
      also observed in children, although in children younger than 6 years of age, the
      normalised mechanical work increases relatively less than the normalised energy
      cost of locomotion. This suggests that young children have a lower efficiency of
      positive muscular work production than adults during walking. Differences in
      normalised mechanical work, energy cost and efficiency between children and
      adults disappear after the age of 10.

PMID- 14718503
TI  - Maternal effects of egg size on emu Dromaius novaehollandiae egg composition and
      hatchling phenotype.
AB  - Parental investment in eggs and, consequently, in offspring can profoundly
      influence the phenotype, survival and ultimately evolutionary fitness of an
      organism. Avian eggs are excellent model systems to examine maternal allocation
      of energy translated through egg size variation. We used the natural range in emu
      Dromaius novaehollandiae egg size, from 400 g to >700 g, to examine the influence
      of maternal investment in eggs on the morphology and physiology of hatchlings.
      Female emus provisioned larger eggs with a greater absolute amount of energy,
      nutrients and water in the yolk and albumen. Variation in maternal investment was
      reflected in differences in hatchling size, which increased isometrically with
      egg size. Egg size also influenced the physiology of developing emu embryos, such
      that late-term embryonic metabolic rate was positively correlated with egg size
      and embryos developing in larger eggs consumed more yolk during development.
      Large eggs produced hatchlings that were both heavier (yolk-free wet and dry
      mass) and structurally larger (tibiotarsus and culmen lengths) than hatchlings
      emerging from smaller eggs. As with many other precocial birds, larger hatchlings
      also contained more water, which was reflected in a greater blood volume.
      However, blood osmolality, hemoglobin content and hematocrit did not vary with
      hatchling mass. Emu maternal investment in offspring, measured by egg size and
      composition, is significantly correlated with the morphology and physiology of
      hatchlings and, in turn, may influence the success of these organisms during the
      first days of the juvenile stage.

PMID- 14718504
TI  - Vocal mechanics in Darwin's finches: correlation of beak gape and song frequency.
AB  - Recent studies of vocal mechanics in songbirds have identified a functional role
      for the beak in sound production. The vocal tract (trachea and beak) filters
      harmonic overtones from sounds produced by the syrinx, and birds can fine-tune
      vocal tract resonance properties through changes in beak gape. In this study, we
      examine patterns of beak gape during song production in seven species of Darwin's
      finches of the Galapagos Islands. Our principal goals were to characterize the
      relationship between beak gape and vocal frequency during song production and to
      explore the possible influence therein of diversity in beak morphology and body
      size. Birds were audio and video recorded (at 30 frames s(-1)) as they sang in
      the field, and 164 song sequences were analyzed. We found that song frequency
      regressed significantly and positively on beak gape for 38 of 56 individuals and
      for all seven species examined. This finding provides broad support for a
      resonance model of vocal tract function in Darwin's finches. Comparison among
      species revealed significant variation in regression y-intercept values. Body
      size correlated negatively with y-intercept values, although not at a
      statistically significant level. We failed to detect variation in regression
      slopes among finch species, although the regression slopes of Darwin's finch and
      two North American sparrow species were found to differ. Analysis within one
      species (Geospiza fortis) revealed significant inter-individual variation in
      regression parameters; these parameters did not correlate with song frequency
      features or plumage scores. Our results suggest that patterns of beak use during
      song production were conserved during the Darwin's finch adaptive radiation,
      despite the evolution of substantial variation in beak morphology and body size.

PMID- 14718505
TI  - Purification and cDNA cloning of the ovigerous-hair stripping substance (OHSS)
      contained in the hatch water of an estuarine crab Sesarma haematocheir.
AB  - The egg attachment system of an estuarine crab Sesarma haematocheir is formed on
      the maternal ovigerous hairs just after egg laying, and slips off these hairs
      just after hatching. The stripping is caused by an active factor that we call
      OHSS (ovigerous-hair stripping substance), which is released by the embryo upon
      hatching. OHSS was purified, and its active form had a molecular mass of 25 kDa.
      The cDNA of OHSS cloned from an embryonic cDNA library was 1759 bp long, encoding
      492 amino acids in a single open reading frame (ORF). The C-terminal part of the
      predicted protein was composed of a trypsin-like serine protease domain, with
      homology to counterparts in other animals of 33-38%. The predicted protein (54.7
      kDa) secreted as a zymogen may be cleaved post-translationally, separating the C
      terminal from the N-terminal region. The OHSS gene was expressed in the embryo at
      least 2 weeks before hatching. Expression was also detected in the zoea larva 1
      day after hatching and in the brain of the female. However, it was not detected
      in the muscle, hepatopancreas or ovigerous seta of the female. Ultrastructural
      analysis indicated that the material investing maternal ovigerous hair, i.e. the
      outermost layer (E1) of the egg case, is attached at the special sites
      (attachment sites) arranged at intervals of 130-160 nm on the hair. It is
      suggested that OHSS acts specifically at these sites, lysing the bond with the
      coat, thus disposing of the embryo attachment system. This enables the female to
      prepare the next clutch of embryos without ecdysis.

PMID- 14718506
TI  - Modular organization of the silkmoth antennal lobe macroglomerular complex
      revealed by voltage-sensitive dye imaging.
AB  - We succeeded in clarifying the functional synaptic organization of the
      macroglomerular complex (MGC) of the male silkmoth Bombyx mori by optical
      recording with a voltage-sensitive dye. Sensory neurons in the antennae send
      their axons down either the medial nerve (MN) or lateral nerve (LN), depending on
      whether they are located on the medial or lateral flagella. Pheromone-sensitive
      fibers in the MN are biased towards the medial MGC, and those in the LN are
      biased towards the lateral MGC in the antennal lobe. In our optical recording
      experiments, the postsynaptic activities in the MGC were characterized by
      pharmacological analysis. Postsynaptic activities in the MGC were separated from
      sensory activities under Ca(2+)-free conditions, and subsequently the inhibitory
      postsynaptic activities were separated by applying bicuculline. We found that the
      inhibitory postsynaptic responses always preceded the postsynaptic responses
      separated under Ca(2+)-free conditions. Moreover, the excitatory postsynaptic
      activities were calculated by subtracting the inhibitory potentials from the
      posysynaptic activities separated under Ca(2+)-free conditions. When the MN was
      stimulated, the amplitudes of the excitatory postsynaptic activities in the
      central toroid, the medial toroid and the medial cumulus were selectively higher
      than those in the other areas. By contrast, when the LN was stimulated,
      excitatory postsynaptic activities were evoked in areas in both the lateral
      toroid and the lateral cumulus. The inhibitory postsynaptic activities were
      equally distributed throughout the whole MGC. These data suggest that there is a
      modular organization to the MGC such that information from the two main branches
      of the antenna is segregated to different sub-regions of the MGC glomeruli.

PMID- 14718507
TI  - Water calcium concentration modifies whole-body calcium uptake in sea bream
      larvae during short-term adaptation to altered salinities.
AB  - Whole-body calcium uptake was studied in gilthead sea bream larvae (9-83 mg) in
      response to changing environmental salinity and [Ca2+]. Calcium uptake increased
      with increased fish size and salinity. Fish exposed to calcium-enriched, diluted
      seawater showed increased calcium uptake compared with fish in diluted seawater
      alone. Calcium uptake was unchanged in Na(+)-enriched, diluted seawater. Overall,
      [Ca2+], and not salinity/osmolarity per se, appears to be the main factor
      contributing to calcium uptake. By contrast, drinking was reduced by a decrease
      in salinity/osmolarity but was little affected by external [Ca2+]. Calculations
      of the maximum contribution from drinking-associated calcium uptake showed that
      it became almost insignificant (less than 10%) through a strong decrease in
      drinking rate at low salinities (0-8 per thousand ). Diluted seawater enriched in
      calcium to the concentration present in full-strength seawater (i.e. constant
      calcium, decreasing salinity) restored intestinal calcium uptake to normal. Extra
      intestinal calcium uptake also benefited from calcium addition but to a lesser
      extent.

PMID- 14718508
TI  - Effects of temperature and anoxia upon the performance of in situ perfused trout
      hearts.
AB  - Rainbow trout (Oncorhynchus mykiss) are likely to experience acute changes in
      both temperature and oxygen availability and, like many other organisms, exhibit
      behavioural selection of low temperatures during hypoxia that acts to reduce
      metabolism and alleviate the demands on the heart. To investigate whether low
      temperature protects cardiac performance during anoxia, we studied the effects of
      an acute temperature change, from 10 degrees C to either 5 degrees C, 15 degrees
      C or 18 degrees C, upon the performance of in situ perfused trout hearts before,
      during and after exposure to 20 min of anoxia. Routine cardiac workload mimicked
      in vivo conditions at the given temperatures, and the effects of anoxia were
      evaluated as maximal cardiac performance before and after 20 min of anoxic
      perfusion. Functional data were related to maximal activities of glycolytic
      enzymes and energetic status of the heart at the termination of the experiment.
      At high oxygenation, maximum cardiac output and power output increased with
      temperature (Q10 values of 1.8 and 2.1, respectively) as a result of increased
      heart rate. Hypoxia tolerance was inversely related to temperature. At 5 degrees
      C, the hearts maintained routine cardiac output throughout the 20 min period of
      anoxia, and maximal cardiac performance was fully restored following
      reoxygenation. By contrast, cardiac function failed sooner during anoxia as
      temperature was increased and maximal performance after reoxygenation was reduced
      by 25%, 35% and 55% at 10 degrees C, 15 degrees C and 18 degrees C, respectively.
      Increased functional impairment following anoxic exposure at elevated temperature
      occurred even though both cardiac glycolytic enzyme activity and the rate of
      lactate production were increased proportionally with cardiac work. Nonetheless,
      there was no indication of myocardial necrosis, as biochemical and energetic
      parameters were generally unaffected by anoxia.

PMID- 14718509
TI  - Moments and power generated by the horse (Equus caballus) hind limb during
      jumping.
AB  - The ability to jump over an obstacle depends upon the generation of work across
      the joints of the propelling limb(s). The total work generated by one hind limb
      of a horse and the contribution to the total work by four joints of the hind limb
      were determined for a jump. It was hypothesized that the hip and ankle joints
      would have extensor moments performing positive work, while the knee would have a
      flexor moment and perform negative work during the jump. Ground reaction forces
      and sagittal plane kinematics were simultaneously recorded during each jumping
      trial. Joint moment, power and work were determined for the metatarsophalangeal
      (MP), tarsal (ankle), tibiofemoral (knee) and coxofemoral (hip) joints. The hip,
      knee and ankle all flexed and then extended and the MP extended and then flexed
      during ground contact. Consistent with our hypothesis, large extensor moments
      were observed at the hip and ankle joints and large flexor moments at the knee
      and MP joints throughout ground contact of the hind limb. Peak moments tended to
      occur earlier in stance in the proximal joints but peak power generation of the
      hind limb joints occurred at similar times except for the MP joint, with the hip
      and ankle peaking first followed by the MP joint. During the first portion of
      ground contact (approximately 40%), the net result of the joint powers was the
      absorption of power. During the remainder of the contact period, the hind limb
      generated power. This pattern of power absorption followed by power generation
      paralleled the power profiles of the hip, ankle and MP joints. The total work
      performed by one hind limb was 0.71 J kg(-1). Surprisingly, the knee produced 85%
      of the work (0.60 J kg(-1)) done by the hind limb, and the positive work
      performed by the knee occurred during the first 40% of the take-off. There is
      little net work generated by the other three joints over the entire take-off.
      Velocity of the tuber coxae (a landmark on the pelvis of the animal) was negative
      (downward) during the first 40% of stance, which perhaps reflects the negative
      work performed to decrease the potential energy during the first 40% of contact.
      During the final 60% of contact, the hip, ankle and MP joints generate positive
      work, which is reflected in the increase of the animal's potential energy.

PMID- 14718510
TI  - Glucose dehydrogenase is required for normal sperm storage and utilization in
      female Drosophila melanogaster.
AB  - Female sperm storage is a key factor for reproductive success in a variety of
      organisms, including Drosophila melanogaster. The spermathecae, one of the
      Drosophila sperm storage organs, has been suggested as a long-term storage organ
      because its secreted substances may enhance the quality of sperm storage. Glucose
      dehydrogenase (GLD) is widely expressed and secreted in the spermathecal ducts
      among species of the genus Drosophila. This highly conserved expression pattern
      suggests that this enzyme might have an important role in female fertility. Here,
      we examine the function of GLD in sperm storage and utilization using Gld-null
      mutant females. The absence of GLD reduced the amount of sperm stored in the
      spermathecae and led to a highly asymmetrical sperm distribution in the two
      spermathecal capsules of the mutant females. The storage defect was especially
      severe when the mutant females were crossed to a Gld-mutant male that had
      previously mated a few hours before the experimental cross. Under this mating
      condition, the mutant females stored in the spermathecae only one-third of the
      sperm amount of the wild-type control females. In addition, the mutant females
      used stored sperm at a slower rate over a longer period compared with wild-type
      females. Thus, our results indicate that GLD facilitates both sperm uptake and
      release through the spermathecal ducts.

PMID- 14718511
TI  - The dichotomous oxyregulatory behaviour of the planktonic crustacean Daphnia
      magna.
AB  - The dual function of appendage movement (food acquisition, ventilation) proved to
      be the key to explaining the peculiar oxyregulatory repertoire of the planktonic
      filter feeder Daphnia magna. Short-term hypoxic exposure experiments with
      normoxia-acclimated animals under varying food concentrations revealed a
      dichotomous response pattern with a compensatory tachycardia under food-free
      conditions and a ventilatory compensation prevailing under food-rich conditions.
      Food-free, normoxic conditions resulted in maximum appendage beating rates (fA)
      and half-maximum heart rates (fH), which restricted the scope for oxyregulation
      to the circulatory system. Food-rich conditions (10(5) algal cells ml(-1)), on
      the contrary, had a depressing effect on fA whereas fH increased to 83% of the
      maximum. In this physiological state, D. magna was able to respond to progressive
      hypoxia with a compensatory increase in ventilation. A conceptual and
      mathematical model was developed to analyse the efficiency of ventilatory and
      circulatory adjustments in improving oxygen transport to tissue. Model
      predictions showed that an increase in perfusion rate was most effective under
      both food-free and food-rich conditions in reducing the critical ambient oxygen
      tension (PO2crit) at which oxygen supply to the tissue started to become impeded.
      By contrast, a hypothetical increase in ventilation rate had almost no effect on
      PO2crit under food-free conditions, indicating that appendage movement is driven
      by nutritive rather than respiratory requirements. However, the model predicted a
      moderate reduction of PO2crit by hyperventilation under food-rich conditions.
      Since the regulatory scope for an adjustment in fH was found to be limited in D.
      magna under these conditions, the increase in ventilation rate is the means of
      choice for a fed animal to cope with short-term, moderate reductions in ambient
      oxygen availability. Under long-term and more severe hypoxic conditions, however,
      the increase in the concentration and oxygen affinity of haemoglobin represents
      the one and only measure for improving the transport of oxygen from environment
      to cells.

PMID- 14718512
TI  - Dynamical analysis reveals individuality of locomotion in goldfish.
AB  - Goldfish swimming was analysed quantitatively to determine if it exhibits
      distinctive individual spatio-temporal patterns. Due to the inherent variability
      in fish locomotion, this hypothesis was tested using five nonlinear measures,
      complemented by mean velocity. A library was constructed of 75 trajectories, each
      of 5 min duration, acquired from five fish swimming in a constant and relatively
      homogeneous environment. Three nonlinear measures, the 'characteristic fractal
      dimension' and 'Richardson dimension', both quantifying the degree to which a
      trajectory departs from a straight line, and 'relative dispersion',
      characterizing the variance as a function of the duration, have coefficients of
      variation less than 7%, in contrast to mean velocity (30%). A discriminant
      analysis, or classification system, based on all six measures revealed that
      trajectories are indeed highly individualistic, with the probability that any two
      trajectories generated from different fish are equivalent being less than 1%.
      That is, the combination of these measures allows a given trajectory to be
      assigned to its source with a high degree of confidence. The Richardson dimension
      and the 'Hurst exponent', which quantifies persistence, were the most effective
      measures.

PMID- 14718513
TI  - Src homology 2-containing 5-inositol phosphatase (SHIP) suppresses an early stage
      of lymphoid cell development through elevated interleukin-6 production by myeloid
      cells in bone marrow.
AB  - The Src homology (SH)2-containing inositol 5-phosphatase (SHIP) negatively
      regulates a variety of immune responses through inhibitory immune receptors. In
      SHIP(-/-) animals, we found that the number of early lymphoid progenitors in the
      bone marrow was significantly reduced and accompanied by expansion of myeloid
      cells. We exploited an in vitro system using hematopoietic progenitors that
      reproduced the in vivo phenotype of SHIP(-/-) mice. Lineage-negative marrow (Lin(
      )) cells isolated from wild-type mice failed to differentiate into B cells when
      cocultured with those of SHIP(-/-) mice. Furthermore, culture supernatants of
      SHIP(-/-) Lin(-) cells suppressed the B lineage expansion of wild-type lineage
      negative cells, suggesting the presence of a suppressive cytokine. SHIP(-/-) Lin(
      ) cells contained more IL-6 transcripts than wild-type Lin(-) cells, and
      neutralizing anti-IL-6 antibody rescued the B lineage expansion suppressed by the
      supernatants of SHIP(-/-) Lin(-) cells. Finally, we found that addition of
      recombinant IL-6 to cultures of wild-type Lin(-) bone marrow cells reproduced the
      phenotype of SHIP(-/-) bone marrow cultures: suppression of B cell development
      and expansion of myeloid cells. The results identify IL-6 as an important
      regulatory cytokine that can suppress B lineage differentiation and drive
      excessive myeloid development in bone marrow.

PMID- 14718514
TI  - Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens
      is not required for the pathogenesis of lupus glomerulonephritis.
AB  - In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic
      glomerulonephritis, severe proteinuria, and early mortality in females. A locus
      Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti-double
      stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two
      congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4
      (NZM.C57Lc4), were generated by replacing the respective genetic intervals
      containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain.
      The NZM.C57Lc1 females had markedly reduced incidence of chronic
      glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic
      glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA,
      and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly,
      NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence
      of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had
      immune complexes by immunofluorescence and electron microscopy. The eluates from
      these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative
      of the presence of non-anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to
      dsDNA and chromatin is not required for the pathogenesis of lupus nephritis.
      These results reaffirm that anti-dsDNA and related Ab production and chronic
      glomerulonephritis are under independent genetic control. These findings have
      significant implications in the pathogenesis of systemic lupus erythematosus.

PMID- 14718515
TI  - Aiolos is required for the generation of high affinity bone marrow plasma cells
      responsible for long-term immunity.
AB  - Antigenic encounter generates long-term immunity sustained by long-lived high
      affinity plasma cells resident in the bone marrow (BM). Here we show that the
      Ikaros family member, Aiolos, is specifically required for the generation of
      these plasma cells. Failure to generate high affinity plasma cells in the BM and
      to sustain serum antibody titers is apparent after both primary and secondary
      immunization of Aiolos(-)(/)(-) mice with a range of hapten concentrations.
      Chimera reconstitutions demonstrate that the BM plasma cell defect is B cell
      intrinsic. Lack of Aiolos does not alter expression of any of the previously
      described factors required for general plasma cell differentiation. No defect in
      somatic hypermutation, the generation of memory B cells, or short-lived high
      affinity plasma cells in the spleen was observed upon rechallenge. These studies
      support a model by which the high affinity plasma cell population in the BM
      undergoes a unique differentiation program that is dependent on Aiolos.

PMID- 14718516
TI  - Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.
AB  - Beta-catenin-mediated Wnt signaling has been suggested to be critically involved
      in hematopoietic stem cell maintenance and development of T and B cells in the
      immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated
      inactivation of the beta-catenin gene in bone marrow progenitors does not impair
      their ability to self-renew and reconstitute all hematopoietic lineages (myeloid,
      erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both
      thymocyte survival and antigen-induced proliferation of peripheral T cells is
      beta-catenin independent. In contrast to earlier reports, these data exclude an
      essential role for beta-catenin during hematopoiesis and lymphopoiesis.

PMID- 14718517
TI  - Differential efficacy of caspase inhibitors on apoptosis markers during sepsis in
      rats and implication for fractional inhibition requirements for therapeutics.
AB  - A rodent model of sepsis was used to establish the relationship between caspase
      inhibition and inhibition of apoptotic cell death in vivo. In this model,
      thymocyte cell death was blocked by Bcl-2 transgene, indicating that apoptosis
      was predominantly dependent on the mitochondrial pathway that culminates in
      caspase-3 activation. Caspase inhibitors, including the selective caspase-3
      inhibitor M867, were able to block apoptotic manifestations both in vitro and in
      vivo but with strikingly different efficacy for different cell death markers.
      Inhibition of DNA fragmentation required substantially higher levels of caspase-3
      attenuation than that required for blockade of other apoptotic events such as
      spectrin proteolysis and phosphatidylserine externalization. These data indicate
      a direct relationship between caspase inhibition and some apoptotic
      manifestations but that small quantities of uninhibited caspase-3 suffice to
      initiate genomic DNA breakdown, presumably through the escape of catalytic
      quantities of caspase-activated DNase. These findings suggest that putative
      caspase-independent apoptosis may be overestimated in some systems since blockade
      of spectrin proteolysis and other cell death markers does not accurately reflect
      the high degrees of caspase-3 inhibition needed to prevent DNA fragmentation.
      Furthermore, this requirement presents substantial therapeutic challenges owing
      to the need for persistent and complete caspase blockade.

PMID- 14718518
TI  - The uniformity of phagosome maturation in macrophages.
AB  - Many studies of endocytosis and phagocytosis presume that organelles containing a
      single kind of internalized particle exhibit invariant patterns of protein and
      phospholipid association as they mature inside cells. To test this presumption,
      fluorescent protein chimeras were expressed in RAW 264.7 macrophages, and time
      lapse ratiometric fluorescence microscopy was used to measure the maturation
      dynamics of individual phagosomes containing IgG-opsonized erythrocytes.
      Quantitative analysis revealed consistent patterns of association for YFP
      chimeras of beta-actin, Rab5a, Rab7, and LAMP-1, and no association of YFP
      chimeras marking endoplasmic reticulum or Golgi. YFP-2xFYVE, recognizing
      phosphatidylinositol 3-phosphate (PI(3)P), showed two patterns of phagosome
      labeling. Some phagosomes increased labeling quickly after phagosome closure and
      then lost the label within 20 min, whereas others labeled more slowly and
      retained the label for several hours. The two patterns of PI(3)P on otherwise
      identical phagosomes indicated that organelle maturation does not necessarily
      follow a single path and that some features of phagosome maturation are
      integrated over the entire organelle.

PMID- 14718519
TI  - GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor.
AB  - The cascade of phosphorylation is a pivotal event in transforming growth factor
      beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental
      aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta
      type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found
      Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory
      subunit of the protein phosphatase 1 (PP1) holoenzyme, which subsequently
      recruits catalytic subunit of PP1 (PP1c) to dephosphorylate TbetaRI. Blocking
      Smad7 expression by RNA interference inhibits association of GADD34-PP1c complex
      with TbetaRI, indicating Smad7 acts as an adaptor protein in the formation of the
      PP1 holoenzyme that targets TbetaRI for dephosphorylation. SARA (Smad anchor for
      receptor activation) enhances the recruitment PP1c to the Smad7-GADD34 complex by
      controlling the specific subcellular localization of PP1c. Importantly, GADD34
      PP1c recruited by Smad7 inhibits TGFbeta-induced cell cycle arrest and mediates
      TGFbeta resistance in responding to UV light irradiation. The dephosphorylation
      of TbetaRI mediated by Smad7 is an effective mechanism for governing negative
      feedback in TGFbeta signaling.

PMID- 14718520
TI  - Intraflagellar transport (IFT) cargo: IFT transports flagellar precursors to the
      tip and turnover products to the cell body.
AB  - Intraflagellar transport (IFT) is the bidirectional movement of multisubunit
      protein particles along axonemal microtubules and is required for assembly and
      maintenance of eukaryotic flagella and cilia. One posited role of IFT is to
      transport flagellar precursors to the flagellar tip for assembly. Here, we
      examine radial spokes, axonemal subunits consisting of 22 polypeptides, as
      potential cargo for IFT. Radial spokes were found to be partially assembled in
      the cell body, before being transported to the flagellar tip by anterograde IFT.
      Fully assembled radial spokes, detached from axonemal microtubules during
      flagellar breakdown or turnover, are removed from flagella by retrograde IFT.
      Interactions between IFT particles, motors, radial spokes, and other axonemal
      proteins were verified by coimmunoprecipitation of these proteins from the
      soluble fraction of Chlamydomonas flagella. These studies indicate that one of
      the main roles of IFT in flagellar assembly and maintenance is to transport
      axonemal proteins in and out of the flagellum.

PMID- 14718521
TI  - Essential role of MARCKS in cortical actin dynamics during gastrulation
      movements.
AB  - Myristoylated alanine-rich C kinase substrate (MARCKS) is an actin-binding,
      membrane-associated protein expressed during Xenopus embryogenesis. We analyzed
      its function in cytoskeletal regulation during gastrulation. Here, we show that
      blockade of its function impaired morphogenetic movements, including convergent
      extension. MARCKS was required for control of cell morphology, motility,
      adhesion, protrusive activity, and cortical actin formation in embryonic cells.
      We also demonstrate that the noncanonical Wnt pathway promotes the formation of
      lamellipodia- and filopodia-like protrusions and that MARCKS is necessary for
      this activity. These findings show that MARCKS regulates the cortical actin
      formation that is requisite for dynamic morphogenetic movements.

PMID- 14718522
TI  - Biochemistry and the sciences of recognition.

PMID- 14718523
TI  - Dimorphecolic acid is synthesized by the coordinate activities of two divergent
      Delta12-oleic acid desaturases.
AB  - Dimorphecolic acid (9-OH-18:2Delta(10)(trans)(,12)(trans)) is the major fatty
      acid of seeds of Dimorphotheca species. This fatty acid contains structural
      features that are not typically found in plant fatty acids, including a C-9
      hydroxyl group, Delta(10),Delta(12)-conjugated double bonds, and trans-Delta(12)
      unsaturation. Expressed sequence tag analysis was conducted to determine the
      biosynthetic origin of dimorphecolic acid. cDNAs for two divergent forms of
      Delta(12)-oleic acid desaturase, designated DsFAD2-1 and Ds-FAD2-2, were
      identified among expressed sequence tags generated from developing Dimorphotheca
      sinuata seeds. Expression of DsFAD2-1 in Saccharomyces cerevisiae and soybean
      somatic embryos resulted in the accumulation of the trans-Delta(12) isomer of
      linoleic acid (18: 2Delta(9)(cis)(,12)(trans)) rather than the more typical cis
      Delta(12) isomer. When co-expressed with DsFAD2-1 in soybean embryos or yeast,
      DsFAD2-2 converted 18:2Delta(9)(cis)(,12)(trans) into dimorphecolic acid. When
      DsFAD2-2 was expressed alone in soybean embryos or together with a typical cis
      Delta(12)-oleic acid desaturase in yeast, trace amounts of the cis-Delta(12)
      isomer of dimorphecolic acid (9-OH-18:2Delta(10)(trans,)(12)(cis)) were formed
      from DsFAD2-2 activity with cis-Delta(12)-linoleic acid [corrected]. These
      results indicate that DsFAD2-2 catalyzes the conversion of the Delta(9) double
      bond of linoleic acid into a C-9 hydroxyl group and Delta(10)(trans) double bond
      and displays a substrate preference for the trans-Delta(12), rather than the cis
      Delta(12), isomer of linoleic acid. Overall these data are consistent with a
      biosynthetic pathway of dimorphecolic acid involving the concerted activities of
      DsFAD2-1 and DsFAD2-2. The evolution of two divergent Delta(12)-oleic acid
      desaturases for the biosynthesis of an unusual fatty acid is unprecedented in
      plants.

PMID- 14718524
TI  - Inactivation of platelet-derived growth factor receptor by the tumor suppressor
      PTEN provides a novel mechanism of action of the phosphatase.
AB  - PTEN, mutated in a variety of human cancers, is a dual specificity protein
      phosphatase and also possesses D3-phosphoinositide phosphatase activity on
      phosphatidylinositol 3,4,5-tris-phosphate (PIP(3)), a product of
      phosphatidylinositol 3-kinase. This PIP(3) phosphatase activity of PTEN
      contributes to its tumor suppressor function by inhibition of Akt kinase, a
      direct target of PIP(3). We have recently shown that Akt regulates PDGF-induced
      DNA synthesis in mesangial cells. In this study, we demonstrate that expression
      of PTEN in mesangial cells inhibits PDGF-induced Akt activation leading to
      reduction in PDGF-induced DNA synthesis. As a potential mechanism, we show that
      PTEN inhibits PDGF-induced protein tyrosine phosphorylation with concomitant
      dephosphorylation and inactivation of tyrosine phosphorylated and activated PDGF
      receptor. Recombinant as well as immunopurified PTEN dephosphorylates
      autophosphorylated PDGF receptor in vitro. Expression of phosphatase deficient
      mutant of PTEN does not dephosphorylate PDGF-induced tyrosine phosphorylated PDGF
      receptor. Rather its expression increases tyrosine phosphorylation of PDGF
      receptor. Furthermore, expression of PTEN attenuated PDGF-induced signal
      transduction including phosphatidylinositol 3-kinase and Erk1/2 MAPK activities.
      Our data provide the first evidence that PTEN is physically associated with
      platelet-derived growth factor (PDGF) receptor and that PDGF causes its
      dissociation from the receptor. Finally, we show that both the C2 and tail
      domains of PTEN contribute to binding to the PDGF receptor. These data
      demonstrate a novel aspect of PTEN function where it acts as an effector for the
      PDGF receptor function and negatively regulates PDGF receptor activation.

PMID- 14718525
TI  - Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces
      pombe.
AB  - Mutations in either TSC1 or TSC2 cause tuberous sclerosis complex, an autosomal
      dominant disorder characterized by seizures, mental retardation, and benign
      tumors of the skin, brain, heart, and kidneys. Homologs for the TSC1 and TSC2
      genes have been identified in mouse, rat, Fugu, Drosophila, and in the yeast
      Schizosaccharomyces pombe. Here we show that S. pombe lacking tsc1+ or tsc2+ have
      similar phenotypes including decreased arginine uptake, decreased expression of
      three amino acid permeases, and low intracellular levels of four members of the
      arginine biosynthesis pathway. Recently, the small GTPase Rheb was identified as
      a target of the GTPase-activating domain of tuberin in mammalian cells and in
      Drosophila. We show that the defect in arginine uptake in cells lacking tsc2+ is
      rescued by the expression of a dominant negative form of rhb1+, the Rheb homolog
      in S. pombe, but not by expressing wild-type rhb1+. Expression of the tsc2+ gene
      with a patient-derived mutation within the GAP domain did not rescue the arginine
      uptake defect in tsc2+ mutant yeast. Taken together, these findings support a
      model in which arginine uptake is regulated through tsc1+, tsc2+, and rhb1+ in S.
      pombe and also suggest a role for the Tsc1 and Tsc2 proteins in amino acid
      biosynthesis and sensing.

PMID- 14718526
TI  - Human disease-related mutations in cytochrome b studied in yeast.
AB  - Several mutations in the mitochondrially encoded cytochrome b have been reported
      in patients. To characterize their effect, we introduced six "human" mutations,
      namely G33S, S152P, G252D, Y279C, G291D, and Delta252-259 in the highly similar
      yeast cytochrome b. G252D showed wild type behavior in standard conditions.
      However, Asp-252 may interfere with structural lipid and, in consequence,
      destabilize the enzyme assembly, which could explain the pathogenicity of the
      mutation. The mutations G33S, S152P, G291D, and Delta252-259 were clearly
      pathogenic. They caused a severe decrease of the respiratory function and altered
      the assembly of the iron-sulfur protein in the bc(1) complex, as observed by
      immunodetection. Suppressor mutations that partially restored the respiratory
      function impaired by S152P or G291D were found in or close to the hinge region of
      the iron-sulfur protein, suggesting that this region may play a role in the
      stable binding of the subunit to the bc(1) complex. Y279C caused a significant
      decrease of the bc(1) function and perturbed the quinol binding. The EPR spectra
      showed an altered signal, indicative of a lower occupancy of the Q(o) site. The
      effect of human mutation of residue 279 was confirmed by another change, Y279A,
      which had a more severe effect on Q(o) site properties. Thus by using yeast as a
      model system, we identified the molecular basis of the respiratory defect caused
      by the disease mutations in cytochrome b.

PMID- 14718527
TI  - Irreversible glucuronyl C5-epimerization in the biosynthesis of heparan sulfate.
AB  - Glucuronyl C5-epimerase catalyzes the conversion of d-glucuronic acid to l
      iduronic acid units in heparan sulfate biosynthesis. Substrate recognition
      depends on the N-substituent pattern of the heparan sulfate precursor
      polysaccharide and requires the adjacent glucosamine residue toward the non
      reducing end to be N-sulfated. Epimerization of an appropriately N-sulfated
      substrate is freely reversible in a soluble system, with equilibrium favoring
      retention of d-gluco configuration (Hagner-McWhirter, A., Lindahl, U., and Li, J.
      P. (2000) Biochem. J. 347, 69-75). We studied the reversibility of the epimerase
      reaction in a cellular system, by incubating human embryonic kidney 293 cells
      with d-[5-(3)H]galactose. The label was incorporated with glucuronic acid units
      into the heparan sulfate precursor polysaccharide and was lost upon subsequent C5
      epimerization to iduronic acid. However, analysis of oligosaccharides obtained by
      deaminative cleavage of the mature heparan sulfate chains indicated that all
      glucuronic acid units retained their C5-(3)H label, irrespective of whether they
      had occurred in sequences susceptible or resistant to the epimerase. All (3)H
      labels of the final products resisted incubation with epimerase in a soluble
      system, apparently due to blocking O-sulfate groups. These results indicate that
      glucuronic acid C5-epimerization is effectively irreversible in vivo and argue
      for a stringent organization of the biosynthetic machinery.

PMID- 14718528
TI  - Quantitative relationships of site to site interaction in Escherichia coli D-3
      phosphoglycerate dehydrogenase revealed by asymmetric hybrid tetramers.
AB  - A set of asymmetric hybrid tetramers of Escherichia coli d-3-phosphoglycerate
      dehydrogenase (PGDH) have been made by gene co-expression and KSCN-induced dimer
      exchange. These tetramers contain varied numbers of active sites and effector
      binding sites arranged in different orientations within the tetramer. They reveal
      that PGDH displays half-of-the-sites activity with respect to its active sites
      and that the two sites that are active at any particular time lie in subunits on
      either side of the nucleotide binding domain interface. Half-of-the-sites
      functionality is also observed for the effector even though all four sites
      eventually bind effector. That is, only two effector sites need to be occupied
      for maximum inhibition. Binding of the last two effector molecules does not
      contribute functionally to inhibition of activity. Furthermore, positive
      cooperativity of inhibition of activity by the effector is completely dependent
      on the positive cooperativity of binding of the effector. Binding of the first
      effector molecule produces a conformational change that essentially completely
      inhibits the active site within the subunit to which it binds and produces an
      approximate 33% inhibition of the active site in the subunit to which it is not
      bound. Binding of the second effector at the opposite regulatory domain interface
      completes the inhibition of activity. This simple relationship defines the
      positional and quantitative influence of effector ligand binding on activity and
      can be used to predict the maximum level of inhibition of individual hybrid
      tetramers. In addition, the site-specific quantitative relationship of effector
      binding to individual active sites can be used to model the inhibition profile
      with relatively good agreement. These simple rules for the site to site
      interaction in PGDH provide significant new insight into the mechanism of
      allostery of this enzyme.

PMID- 14718529
TI  - A novel NAD-binding protein revealed by the crystal structure of 2,3-diketo-L
      gulonate reductase (YiaK).
AB  - Escherichia coli YiaK catalyzes the reduction of 2,3-diketo-L-gulonate in the
      presence of NADH. It belongs to a large family of oxidoreductases that is
      conserved in archaea, bacteria, and eukaryotes but shows no sequence homology to
      other proteins. We report here the crystal structures at up to 2.0-A resolution
      of YiaK alone and in complex with NAD-tartrate. YiaK has a new polypeptide
      backbone fold and a novel mode of recognizing the NAD cofactor. In addition, NAD
      is bound in an unusual conformation, at the interface of a dimer of the enzyme.
      The crystallographic analysis unexpectedly revealed the binding of tartrate in
      the active site. Enzyme kinetics studies confirm that tartrate and the related D
      malate are inhibitors of YiaK. In contrast to most other enzymes where substrate
      binding produces a more closed conformation, the binding of NAD-tartrate to YiaK
      produces a more open active site. The free enzyme conformation is incompatible
      with NAD binding. His(44) is likely the catalytic residue of the enzyme.

PMID- 14718530
TI  - Hsp72 interacts with paxillin and facilitates the reassembly of focal adhesions
      during recovery from ATP depletion.
AB  - The cytoprotective effect of heat stress proteins on epithelial cell detachment,
      an important cause of acute, ischemic renal failure, was examined after ATP
      depletion by evaluating focal adhesion complex (FAC) integrity. The intracellular
      distribution of FAC proteins (paxillin, talin, and vinculin) was assessed by
      immunohistochemistry before, during, and after exposure of renal epithelial cells
      to metabolic inhibitors. The resulting ATP depletion caused reversible re
      distribution of all three proteins from focal adhesions to the cytosol. Paxillin,
      a key adaptor protein, was selected as a surrogate marker for FAC integrity in
      subsequent studies. Prior heat stress increased hsp72, a molecular chaperone, in
      both the Triton X-100-soluble and -insoluble protein fractions. Compared with ATP
      depleted control, heat stress significantly decreased paxillin and hsp72 shift
      from the Triton X-100 soluble to the insoluble protein fraction (an established
      marker of denaturation and aggregation); increased paxillin-hsp72 interaction
      detected by co-immunoprecipitation; enhanced paxillin extractability from Triton
      X-100-insoluble precipitates, increased the reformation of focal adhesions, and
      improved cell attachment (p < 0.05). To determine whether hsp72 mediates
      protection afforded by heat stress, cells were infected with adenovirus
      containing human hsp72 or empty vector. Hsp72 overexpression increased its
      interaction with paxillin and improved focal adhesion reformation during
      recovery, mimicking the protective effects of heat stress. These data suggest
      that hsp72 facilitates the reassembly of focal adhesions and improves cell
      attachment by reducing paxillin denaturation and increasing its re-solubilization
      after ATP depletion.

PMID- 14718531
TI  - Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-beta forming a
      phosphohistidine enzyme intermediate during catalysis.
AB  - The glucose-6-phosphatase (Glc-6-Pase) family comprises two active endoplasmic
      reticulum (ER)-associated isozymes: the liver/kidney/intestine Glc-6-Pase-alpha
      and the ubiquitous Glc-6-Pase-beta. Both share similar kinetic properties.
      Sequence alignments predict the two proteins are structurally similar. During
      glucose 6-phosphate (Glc-6-P) hydrolysis, Glc-6-Pase-alpha, a nine-transmembrane
      domain protein, forms a covalently bound phosphoryl enzyme intermediate through
      His(176), which lies on the lumenal side of the ER membrane. We showed that Glc-6
      Pase-beta is also a nine-transmembrane domain protein that forms a covalently
      bound phosphoryl enzyme intermediate during Glc-6-P hydrolysis. However, the
      intermediate was not detectable in Glc-6-Pase-beta active site mutants R79A,
      H114A, and H167A. Using [(32)P]Glc-6-P coupled with cyanogen bromide mapping, we
      demonstrated that the phosphate acceptor in Glc-6-Pase-beta is His(167) and that
      it lies inside the ER lumen with the active site residues, Arg(79) and His(114).
      Therefore Glc-6-Pase-alpha and Glc-6-Pase-beta share a similar active site
      structure, topology, and mechanism of action.

PMID- 14718532
TI  - pH-induced conversion of the transport lectin ERGIC-53 triggers glycoprotein
      release.
AB  - The recycling mannose lectin ERGIC-53 operates as a transport receptor by
      mediating efficient endoplasmic reticulum (ER) export of some secretory
      glycoproteins. Binding of cargo to ERGIC-53 in the ER requires Ca2+. Cargo
      release occurs in the ERGIC, but the molecular mechanism is unknown. Here we
      report efficient binding of purified ERGIC-53 to immobilized mannose at pH 7.4,
      the pH of the ER, but not at slightly lower pH. pH sensitivity of the lectin was
      more prominent when Ca2+ concentrations were low. A conserved histidine in the
      center of the carbohydrate recognition domain was required for lectin activity
      suggesting it may serve as a molecular pH/Ca2+ sensor. Acidification of cells
      inhibited the association of ERGIC-53 with the known cargo cathepsin Z-related
      protein and dissociation of this glycoprotein in the ERGIC was impaired by
      organelle neutralization that did not impair the transport of a control protein.
      The results elucidate the molecular mechanism underlying reversible lectin/cargo
      interaction and establish the ERGIC as the earliest low pH site of the secretory
      pathway.

PMID- 14718533
TI  - The role of the carboxyl terminus in ClC chloride channel function.
AB  - The human muscle chloride channel ClC-1 has a 398-amino acid carboxyl-terminal
      domain that resides in the cytoplasm and contains two CBS (cystathionine-beta
      synthase) domains. To examine the role of this region, we studied various
      carboxyl-terminal truncations by heterologous expression in mammalian cells,
      whole-cell patch clamp recording, and confocal imaging. Channel constructs
      lacking parts of the distal CBS domain, CBS2, did not produce functional
      channels, whereas deletion of CBS1 was tolerated. ClC channels are dimeric
      proteins with two ion conduction pathways (protopores). In heterodimeric channels
      consisting of one wild type subunit and one subunit in which the carboxyl
      terminus was completely deleted, only the wild type protopore was functional,
      indicating that the carboxyl terminus supports the function of the protopore. All
      carboxyl-terminal-truncated mutant channels fused to yellow fluorescent protein
      were translated and the majority inserted into the plasma membrane as revealed by
      confocal microscopy. Fusion proteins of cyan fluorescent protein linked to
      various fragments of the carboxyl terminus formed soluble proteins that could be
      redistributed to the surface membrane through binding to certain truncated
      channel subunits. Stable binding only occurs between carboxyl-terminal fragments
      of a single subunit, not between carboxyl termini of different subunits and not
      between carboxyl-terminal and transmembrane domains. However, an interaction with
      transmembrane domains can modify the binding properties of particular carboxyl
      terminal proteins. Our results demonstrate that the carboxyl terminus of ClC-1 is
      not necessary for intracellular trafficking but is critical for channel function.
      Carboxyl termini fold independently and modify individual protopores of the
      double-barreled channel.

PMID- 14718534
TI  - S-adenosylmethionine decarboxylase degradation by the 26 S proteasome is
      accelerated by substrate-mediated transamination.
AB  - The short-lived enzyme S-adenosylmethionine decarboxylase uses a covalently bound
      pyruvoyl cofactor to catalyze the formation of decarboxylated S
      adenosylmethionine, which then donates an aminopropyl group for polyamine
      biosynthesis. Here we demonstrate that S-adenosylmethionine decarboxylase is
      ubiquitinated and degraded by the 26 S proteasome in vivo, a process that is
      accelerated by inactivation of S-adenosylmethionine decarboxylase by substrate
      mediated transamination of its pyruvoyl cofactor. Proteasome inhibition in COS-7
      cells prevents the degradation of S-adenosylmethionine decarboxylase antigen;
      however, even brief inhibition of the 26 S proteasome caused substantial losses
      of S-adenosylmethionine decarboxylase activity despite accumulation of S
      adenosylmethionine decarboxylase antigen. Levels of the enzyme's substrate (S
      adenosylmethionine) increased rapidly after 26 S proteasome inhibition, and this
      increase in substrate level is consistent with the observed loss of activity
      arising from an increased rate of inactivation by substrate-mediated
      transamination. Evidence is also presented that this substrate-mediated
      transamination accelerates normal degradation of S-adenosylmethionine
      decarboxylase, as the rate of degradation of the enzyme was increased in the
      presence of AbeAdo (5'-([(Z)-4-amino-2-butenyl]methylamino]-5'-deoxyadenosine) (a
      substrate analogue that transaminates the enzyme); conversely, when the
      intracellular substrate level was reduced by methionine deprivation, the rate of
      degradation of the enzyme was decreased. Ubiquitination of S-adenosylmethionine
      decarboxylase is demonstrated by isolation of His-tagged AdoMetDC (S
      adenosylmethionine decarboxylase) from COS-7 cells co-transfected with
      hemagglutinin-tagged ubiquitin and showing bands that were immunoreactive to both
      anti-AdoMetDC antibody and anti-hemagglutinin antibody. This is the first study
      to demonstrate that AdoMetDC is ubiquitinated and degraded by the 26 S
      proteasome, and substrate-mediated acceleration of degradation is a unique
      finding.

PMID- 14718535
TI  - Properties of GDP-mannose pyrophosphorylase, a critical enzyme and drug target in
      Leishmania mexicana.
AB  - Leishmania parasites synthesize a range of mannose-containing glycoconjugates
      thought to be essential for virulence in the mammalian host and sandfly vector. A
      prerequisite for the synthesis of these molecules is the availability of the
      activated mannose donor, GDP-Man, the product of the catalysis of mannose-1
      phosphate and GTP by GDP-mannose pyrophosphorylase (GDP-MP). In contrast to the
      lethal phenotype in fungi, the deletion of the gene in Leishmania mexicana did
      not affect parasite viability but led to a total loss of virulence, making GDP-MP
      an ideal target for anti-Leishmania drug development. We show by
      immunofluorescence and subcellular fractionation that GDP-MP is a cytoplasmic
      protein, and we describe a colorimetric activity assay suitable for the high
      throughput screening of small molecule inhibitors. We expressed recombinant GDP
      MP as a fusion with maltose-binding protein and separated the enzyme from maltose
      binding protein by thrombin cleavage, ion-exchange, and size exclusion
      chromatography. Size exclusion chromatography and analytical ultracentrifugation
      studies demonstrate that GDP-MP self-associates to form an enzymatically active
      and stable hexamer. However, sedimentation studies show that the GDP-MP hexamer
      dissociates to trimers and monomers in a time-dependent manner, at low protein
      concentrations, at low ionic strength, and at alkaline pH. Circular dichroism
      spectroscopy reveals that GDP-MP is comprised of mixed alpha/beta structure,
      similar to its closest related homologue, N-acetyl-glucoseamine-1-phosphate
      uridyltransferase (Glmu) from Streptococcus pneumoniae. Our studies provide
      insight into the structure of a novel target for the development of anti
      Leishmania drugs.

PMID- 14718536
TI  - Gene expression changes associated with the endoplasmic reticulum stress response
      induced by microsomal cytochrome p450 overproduction.
AB  - Induction of drug-metabolizing microsomal cytochromes p450 (p450s) results in a
      striking proliferation of the smooth endoplasmic reticulum (ER). Overexpression
      of P450s in yeast and cultured cells produces a similar response. The signals
      mediating this process are not known but probably involve signal transduction
      pathways involved in the unfolded protein response (UPR) or the ER overload
      response (EOR). We have examined the temporal response of specific genes in these
      pathways and genes globally to overexpression of p450 in cultured cells. Activity
      of NFkappaB, an EOR component, was substantially increased by overexpression of
      full-length p450 2C2 or a chimera with the 28-amino acid signal anchor sequence
      of p450 2C2 in HepG2 cells, and the activation correlated temporally with the
      accumulation of p450 in the cells. In the UPR pathway, activation of the
      transcription factor XBP1 by IRE1 also correlated with the accumulation of p450
      in the cells, and in contrast, maximum activation of the BiP/grp78 promoter
      preceded the accumulation. Differential effects of expression of p450 on
      apoptosis were observed in nonhepatic COS1 and hepatic HepG2 cells. In COS1
      cells, apoptosis was induced, and this correlated with sustained activation of
      the pro-apoptotic JNK pathway, induction of CHOP, and an absence of the increased
      NFkappaB activity. In HepG2 cells, JNK was only transiently activated, and CHOP
      expression was not induced. As assessed by DNA microarray analysis, up-regulation
      of signaling genes was predominant including those involved in anti-apoptosis and
      ER stress. These results suggest that both the EOR and UPR pathways are involved
      in the cellular response to induction of p450 expression and that in hepatic
      cells genes are also induced to block apoptosis, which may be a physiologically
      relevant response to prevent cell death during xenobiotic induced expression of
      p450 in the liver.

PMID- 14718537
TI  - Marlin-1, a novel RNA-binding protein associates with GABA receptors.
AB  - GABA(B) receptors are heterodimeric G protein-coupled receptors that mediate slow
      synaptic inhibition in the central nervous system. Whereas heterodimerization
      between GABA(B) receptor GABA(B)R1 and GABA(B)R2 subunits is essential for
      functional expression, how neurons coordinate the assembly of these critical
      receptors remains to be established. Here we have identified Marlin-1, a novel
      GABA(B) receptor-binding protein that associates specifically with the GABA(B)R1
      subunit in yeast, tissue culture cells, and neurons. Marlin-1 is expressed in the
      brain and exhibits a granular distribution in cultured hippocampal neurons.
      Marlin-1 binds different RNA species including the 3'-untranslated regions of
      both the GABA(B)R1 and GABA(B)R2 mRNAs in vitro and also associates with RNA in
      cultured neurons. Inhibition of Marlin-1 expression via small RNA interference
      technology results in enhanced intracellular levels of the GABA(B)R2 receptor
      subunit without affecting the level of GABA(B)R1. Together our results suggest
      that Marlin-1 functions to regulate the cellular levels of GABA(B) R2 subunits,
      which may have significant effects on the production of functional GABA(B)
      receptor heterodimers. Therefore, our observations provide an added level of
      regulation for the control of GABA(B) receptor expression and for the efficacy of
      inhibitory synaptic transmission.

PMID- 14718538
TI  - Scavenger receptor class B type I-mediated cholesteryl ester-selective uptake and
      efflux of unesterified cholesterol. Influence of high density lipoprotein size
      and structure.
AB  - Scavenger receptor (SR)-BI catalyzes the selective uptake of cholesteryl ester
      (CE) from high density lipoprotein (HDL) by a two-step process that involves the
      following: 1) binding of HDL to the receptor and 2) diffusion of the CE molecules
      into the cell plasma membrane. We examined the effects of the size of discoidal
      HDL particles containing wild-type (WT) apoA-I on selective uptake of CE and
      efflux of cellular free (unesterified) cholesterol (FC) from COS-7 cells
      expressing SR-BI to determine the following: 1) the influence of apoA-I
      conformation on the lipid transfer process, and 2) the contribution of receptor
      binding-dependent processes to the overall efflux of cellular FC. Large (10 nm
      diameter) reconstituted HDL bound to SR-BI better (B(max) approximately 420
      versus 220 ng of apoA-I/mg cell protein), delivered more CE, and promoted more FC
      efflux than small ( approximately 8 nm) particles. When normalized to the number
      of reconstituted HDL particles bound to the receptor, the efficiencies of either
      CE uptake or FC efflux with these particles were the same indicating that
      altering the conformation of WT apoA-I modulates binding to the receptor (step 1)
      but does not change the efficiency of the subsequent lipid transfer (step 2);
      this implies that binding induces an optimal alignment of the WT apoA-I.SR-BI
      complex so that the efficiency of lipid transfer is always the same. FC efflux to
      HDL is affected both by binding of HDL to SR-BI and by the ability of the
      receptor to perturb the packing of FC molecules in the cell plasma membrane.

PMID- 14718539
TI  - Helix stability confers salt resistance upon helical antimicrobial peptides.
AB  - Salt sensitivity of antimicrobial peptides poses a major obstacle in their
      development as novel antibiotics. Here we report the use of helix-capping motifs
      to confer salt resistance upon helical antimicrobial peptides. The helical
      content of the template peptide [RLLR](5) was almost completely destroyed at salt
      concentrations over 200 mm NaCl, leading to a 8-32-fold decrease in antimicrobial
      activity. However, the introduction of helix-capping motifs at the helix termini
      resulted in a structurally stable peptide, which retained membrane-permeabilizing
      and antimicrobial activities upon exposure to salt. Furthermore, the peptide with
      helix-capping motifs directly inhibited the in vivo growth of Streptococcus
      pyogenes, which causes localized fasciitis in mice, and prevented the necrosis of
      the epidermis, dermis, and subcutaneous muscle layers. Results indicate that the
      adoption of helix-capping motifs into salt-sensitive antimicrobial peptides
      provides the necessary structural stability for the peptides to permeabilize cell
      membranes and cause cell death at physiological salt concentrations.

PMID- 14718540
TI  - The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis
      of lysosome-related organelles complex-2 (BLOC-2).
AB  - Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease
      affecting vesicle trafficking among lysosome-related organelles. The Hps3, Hps5,
      and Hps6 genes are mutated in the cocoa, ruby-eye-2, and ruby-eye mouse pigment
      mutants, respectively, and their human orthologs are mutated in HPS3, HPS5, and
      HPS6 patients. These three genes encode novel proteins of unknown function. The
      phenotypes of Hps5/Hps5,Hps6/Hps6 and Hps3/Hps3,Hps6/Hps6 double mutant mice
      mimic, in coat and eye colors, in melanosome ultrastructure, and in levels of
      platelet dense granule serotonin, the corresponding phenotypes of single mutants.
      These facts suggest that the proteins encoded by these genes act within the same
      pathway or protein complex in vivo to regulate vesicle trafficking. Further, the
      Hps5 protein is destabilized within tissues of Hps3 and Hps6 mutants, as is the
      Hps6 protein within tissues of Hps3 and Hps5 mutants. Also, proteins encoded by
      these genes co-immunoprecipitate and occur in a complex of 350 kDa as determined
      by sucrose gradient and gel filtration analyses. Together, these results indicate
      that the Hps3, Hps5, and Hps6 proteins regulate vesicle trafficking to lysosome
      related organelles at the physiological level as components of the BLOC-2
      (biogenesis of lysosome-related organelles complex-2) protein complex and suggest
      that the pathogenesis and future therapies of HPS3, HPS5, and HPS6 patients are
      likely to be similar. Interaction of the Hps5 and Hps6 proteins within BLOC-2 is
      abolished by the three-amino acid deletion in the Hps6(ru) mutant allele,
      indicating that these three amino acids are important for normal BLOC-2 complex
      formation.

PMID- 14718541
TI  - MOCA induces membrane spreading by activating Rac1.
AB  - The modifier of cell adhesion protein (MOCA), or Dock3, initially identified as
      presenilin-binding protein (PBP), belongs to the Dock180 family of proteins and
      is localized specifically in neurons. Here we demonstrate that MOCA binds to Rac1
      and enhances its activity, which leads to the activation of c-Jun NH(2)-terminal
      kinase (JNK) and causes changes in cell morphology. Farnesylated MOCA, which is
      localized in the plasma membrane, enhances the activation of Rac1 and JNK more
      markedly than wild-type MOCA, and cells expressing farnesylated MOCA show
      flattened morphology similar to those expressing a constitutive active mutant of
      Rac1, Rac1Q61L. On poly-d-lysine-coated dishes, endogenous MOCA is concentrated
      on the leading edge of broad membrane protrusions (lamellipodia) where actin
      filaments are co-localized. MOCA is also concentrated with actin on the growth
      cone in primary cultures of cortical neurons. These observations suggest that
      MOCA may induce cytoskeletal reorganization and changes in cell adhesion by
      regulating the activity of Rac1.

PMID- 14718542
TI  - A novel membrane protein capable of binding the Na+/H+ antiporter (Nha1p)
      enhances the salinity-resistant cell growth of Saccharomyces cerevisiae.
AB  - The Na+/H+ antiporter Nha1p of Saccharomyces cerevisiae plays an important role
      in maintaining intracellular pH and Na+ homeostasis. Nha1p has a two-domain
      structure composed of integral membrane and hydrophilic tail regions.
      Overexpression of a peptide of approximately 40 residues (C1+C2 domains) that is
      localized in the juxtamembrane area of its cytoplasmic tail caused cell growth
      retardation in highly saline conditions, possibly by decreasing Na+/H+ antiporter
      activity. A multicopy suppressor gene of this growth retardation was identified
      from a yeast genome library. The clone encodes a novel membrane protein denoted
      as COS3 in the genome data base. Overexpression or deletion of COS3 increases or
      decreases salinity-resistant cell growth, respectively. However, in nha1Delta
      cells, overexpression of COS3 alone did not suppress the growth retardation.
      Cos3p and a hydrophilic portion of Cos3p interact with the C1+C2 peptide in
      vitro, and Cos3p is co-precipitated with Nha1p from yeast cell extracts. Cos3p
      GFP mainly resides at the vacuole, but overexpression of Nha1p caused a portion
      of the Cos3p-GFP proteins to shift to the cytoplasmic membrane. These
      observations suggest that Cos3p is a novel membrane protein that can enhance
      salinity-resistant cell growth by interacting with the C1+C2 domain of Nha1p and
      thereby possibly activating the antiporter activity of this protein.

PMID- 14718543
TI  - p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell
      morphogenesis and is regulated by Smad1.
AB  - Bone morphogenetic protein (BMP)-7 exerts dose-dependent stimulatory and
      inhibitory effects during renal branching morphogenesis. Previously, we
      identified an inhibitory role for activin-like kinase receptors and Smad1 in BMP
      dependent inhibition (Piscione, T. D., Phan, T., and Rosenblum, N. D. (2001) Am.
      J. Physiol. 280, F19-F33). Here we demonstrate a novel role for p38 mitogen
      activated kinase (p38(MAPK)) in BMP7-dependent stimulatory signaling. Stimulatory
      doses (0.25 nm) of BMP7 increased p38(MAPK) activity and stimulated
      phosphorylation of endogenous activating transcription factor 2 (ATF2) in a
      p38(MAPK)-dependent manner in murine inner medullary collecting duct (mIMCD-3)
      cells. In contrast, high doses (10 nm) of BMP7 inhibited p38(MAPK) activity and
      phosphorylation of endogenous ATF2. Treatment with BMP7 exerted no significant
      effect on the levels of the phosphorylated forms of endogenous SAPK/JNK or p44
      and p42 (ERK1 and ERK2) protein kinases. To investigate the functional importance
      of p38(MAPK) signaling, we showed that SB203580, a p38(MAPK) inhibitor, blocked
      the stimulatory effect of BMP7 on mIMCD-3 cell morphogenesis but had no effect on
      BMP7-dependent inhibition in a three-dimensional culture model. To identify
      mechanisms by which BMP7-dependent inhibitory signaling suppresses p38(MAPK)
      activity, we measured p38(MAPK) activity in ligand independent mIMCD-3 models of
      enhanced and suppressed Smad signaling. Basal activity of p38(MAPK) was decreased
      in mIMCD-3 cells and in embryonic kidney tissue expressing a constitutively
      active activin-like kinase receptor, but was increased in mIMCD-3 cells stably
      expressing a dominant negative form of Smad1. We conclude that BMP7 stimulates
      renal epithelial cell morphogenesis via p38(MAPK) and that p38(MAPK) activity is
      negatively regulated by Smad1.

PMID- 14718544
TI  - Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a
      new member of the Cupin superfamily. A possible multifunctional protein acting as
      an invasion suppressor down-regulated in tumors.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) is an enzyme that
      promotes tumor cell invasion in tissues. Although the proteolytic activity of MT1
      MMP is indispensable for invasion, it is also regulated by functions of the
      cytoplasmic tail. In this study we obtained a new human gene whose product binds
      to the tail sequence in yeast. The product, MTCBP-1, is a 19-kDa protein that
      belongs to the newly proposed Cupin superfamily composed of proteins with diverse
      functions. MTCBP-1 expressed in cells formed a complex with MT1-MMP and co
      localized at the membrane. It was also detected in both the cytoplasm and
      nucleus, where MT1-MMP does not exist. In human tumor cell lines MTCBP-1
      expression was significantly low compared with non-transformed fibroblasts, and
      enforced expression of MTCBP-1 inhibited the activity of MT1-MMP in promoting
      cell migration and invasion. MTCBP-1 showed significant homology to the bacterial
      aci-reductone dioxygenase, which is an enzyme in methionine metabolism. The C
      terminal part of MTCBP-1 is identical to Sip-L, which is reported to be important
      for human hepatitis C virus replication. Thus, MTCBP-1 may have multiple
      functions other than the regulation of MT1-MMP, which presumably depends on the
      subcellular compartment.

PMID- 14718545
TI  - Potent inhibition of Ca2+ release-activated Ca2+ channels and T-lymphocyte
      activation by the pyrazole derivative BTP2.
AB  - Ca2+ entry through store-operated Ca2+release-activated Ca2+ (CRAC) channels is
      essential for T-cell activation and proliferation. Recently, it has been shown
      that 3,5-bistrifluoromethyl pyrazole (BTP) derivatives are specific inhibitors of
      Ca2+-dependent transcriptional activity in T-cells (Trevillyan, J. M., Chiou, X.
      G., Chen, Y. W., Ballaron, S. J., Sheets, M. P., Smith, M. L., Wiedeman, P. E.,
      Warrior, U., Wilkins, J., Gubbins, E. J., Gagne, G. D., Fagerland, J., Carter, G.
      W., Luly, J. R., Mollison, K. W., and Djuric, S. W. (2001) J. Biol. Chem. 276,
      48118-48126). Whereas inhibition of Ca2+ signals was reported for BTP2 (Ishikawa,
      J., Ohga, K., Yoshino, T., Takezawa, R., Ichikawa, A., Kubota, H., and Yamada, T.
      (2003) J. Immunol. 170, 4441-4449), it was not found for BTP3 (Chen, Y., Smith,
      M. L., Chiou, G. X., Ballaron, S., Sheets, M. P., Gubbins, E., Warrior, U.,
      Wilkins, J., Surowy, C., Nakane, M., Carter, G. W., Trevillyan, J. M., Mollison,
      K., and Djuric, S. W. (2002) Cell. Immunol. 220, 134-142). We show that BTP2
      specifically inhibits CRAC channels in T-cells with an IC(50) of approximately 10
      nm. It does not interfere with other mechanisms important for Ca2+ signals in T
      cells, including Ca2+ pumps, mitochondrial Ca2+ signaling, endoplasmic reticulum
      Ca2+ release, and K+ channels. BTP2 inhibits Ca2+ signals in peripheral blood T
      lymphocytes (in particular in CD4+ T-cells) and in human Jurkat T-cells.
      Inhibition of Ca2+ signals is independent of the stimulation method as Ca2+ entry
      was blocked following stimulation with anti-CD3, which activates the T-cell
      receptor, and also following stimulation with thapsigargin or inositol 1,4,5
      trisphosphate. BTP2 also inhibited Ca2+-dependent gene expression (interleukins 2
      and 5 and interferon gamma) and proliferation of T-lymphocytes with similar
      IC(50) values. BTP2 is the first potent and specific inhibitor of CRAC channels
      in primary T-lymphocytes. The inhibition of CRAC channels as well as Ca2+
      dependent signal transduction with similar IC(50) values in T-lymphocytes
      emphasizes the importance of CRAC channel activity during T-cell activation.
      Furthermore, BTP2 could prove to be a tool to finally unmask the molecular
      identity of CRAC channels.

PMID- 14718546
TI  - Regulation of binding of lamin B receptor to chromatin by SR protein kinase and
      cdc2 kinase in Xenopus egg extracts.
AB  - Participation of multiple kinases in regulation of the binding of lamin B
      receptor (LBR) to chromatin was suggested previously (Takano, M., Takeuchi, M.,
      Ito, H., Furukawa, K., Sugimoto, K., Omata, S., and Horigome, T. (2002) Eur. J.
      Biochem. 269, 943-953). To identify these kinases, regulation of the binding of
      the nucleoplasmic region (NK, amino acid residues 1-211) of LBR to sperm
      chromatin was studied using a cell cycle-dependent Xenopus egg extract in vitro.
      The binding was stimulated on specific phosphorylation of the NK fragment by an S
      phase egg extract. Protein depletion with beads bearing SF2/ASF, which binds SR
      protein kinases, abolished this stimulation, suggesting that an SR protein
      kinase(s) is responsible for the activation of LBR. This was confirmed by direct
      phosphorylation and activation with recombinant SR protein-specific kinase 1. The
      binding of the NK fragment to chromatin pretreated with an S-phase extract was
      suppressed by incubation with an M-phase extract. Enzyme inhibitor experiments
      revealed that multiple kinases participate in the suppression. One of these
      kinases was shown to be cdc2 kinase using a specific inhibitor, roscovitine, and
      protein depletion with beads bearing p13, which specifically binds cdc2 kinase.
      Experiments involving a mutant NK fragment showed that the phosphorylation of
      serine 71 by cdc2 kinase is responsible for the suppression.

PMID- 14718547
TI  - Identification on mouse chromosome 8 of new beta-defensin genes with regionally
      specific expression in the male reproductive organ.
AB  - Defensins are important elements in innate immunity that can also trigger
      adaptive immune responses. The defensins form a family of small cationic
      antimicrobial peptides with six characteristic cysteine residues, whose pairing
      pattern in forming three intramolecular disulfide bonds defines the alpha- and
      beta-defensin subfamilies. In a search for new beta-defensin genes, we performed
      computational analysis using the Celera mouse genome data base and found exons
      encoding 23 different beta-defensins, including the eight previously
      characterized members of this family. Among the new beta-defensins, nine of them
      form two groups of phylogenetically related sequences that were characterized in
      greater detail. Northern blot, reverse transcription PCR, and in situ
      hybridization analysis showed that expression of these genes is restricted to the
      epididymis, with a specific regional expression pattern. One of the new beta
      defensins (Defb38) was chemically synthesized; in in vitro assays on Gram
      positive and -negative bacterial strains, Defb38 showed the characteristic salt
      dependent antimicrobial activity of beta-defensins. The results demonstrate the
      existence of a relatively large number of beta-defensins with specific expression
      in distinct regions of the murine epididymis and suggest complex roles for these
      proteins in host defense and other physiological processes of the male
      reproductive tract.

PMID- 14718548
TI  - Modifications of the 3'-UTR stem-loop of infectious bursal disease virus are
      allowed without influencing replication or virulence.
AB  - Many questions regarding the initiation of replication and translation of the
      segmented, double-stranded RNA genome of infectious bursal disease virus (IBDV)
      remain to be solved. Computer analysis shows that the non-polyadenylated extreme
      3'-untranslated regions (UTRs) of the coding strand of both genomic segments are
      able to fold into a single stem-loop structure. To assess the determinants for a
      functional 3'-UTR, we mutagenized the 3'-UTR stem-loop structure of the B
      segment. Rescue of infectious virus from mutagenized cDNA plasmids was impaired
      in all cases. However, after one passage, the replication kinetics of these
      viruses were restored. Sequence analysis revealed that additional mutations had
      been acquired in most of the stem-loop structures, which compensated the
      introduced ones. A rescued virus with a modified stem-loop structure containing
      four nucleotide substitutions, but preserving its overall secondary structure,
      was phenotypically indistinguishable from wild-type virus, both in vitro (cell
      culture) and in vivo (chickens, natural host). Sequence analysis showed that the
      modified stem-loop structure of this virus was fully preserved after four serial
      passages. Apparently, it is the stem-loop structure and not the primary sequence
      that is the functional determinant in the 3'-UTRs of IBDV.

PMID- 14718549
TI  - ARC-1, a sequence element complementary to an internal 18S rRNA segment, enhances
      translation efficiency in plants when present in the leader or intercistronic
      region of mRNAs.
AB  - The sequences of different plant viral leaders with known translation enhancer
      ability show partial complementarity to the central region of 18S rRNA. Such
      complementarity might serve as a means to attract 40S ribosomal subunits and
      explain in part the translation-enhancing property of these sequences. To verify
      this notion, we designed beta-glucuronidase (GUS) mRNAs differing only in the
      nature of 10 nt inserts in the center of their 41 base leaders. These were
      complementary to consecutive domains of plant 18S rRNA. Sucrose gradient analysis
      revealed that leaders with inserts complementary to regions 1105-1114 and 1115
      1124 ('ARC-1') of plant 18S rRNA bound most efficiently to the 40S ribosomal
      subunit after dissociation from 80S ribosomes under conditions of high ionic
      strength, a treatment known to remove translation initiation factors. Using wheat
      germ cell-free extracts, we could demonstrate that mRNAs with these leaders were
      translated more than three times more efficiently than a control lacking such a
      complementarity. Three linked copies of the insert enhanced translation of
      reporter mRNA to levels comparable with those directed by the natural translation
      enhancing leaders of tobacco mosaic virus and potato virus Y RNAs. Moreover,
      inserting the same leaders as intercistronic sequences in dicistronic mRNAs
      substantially increased translation of the second cistron, thereby revealing
      internal ribosome entry site activity. Thus, for plant systems, the complementary
      interaction between mRNA leader and the central region of 18S rRNA allows cap
      independent binding of mRNA to the 43S pre-initiation complex without assistance
      of translation initiation factors.

PMID- 14718550
TI  - The guanine-rich fragile X chromosome repeats are reluctant to form tetraplexes.
AB  - Using circular dichroism spectroscopy, UV absorption spectroscopy and
      polyacrylamide gel electrophoresis, we studied conformational properties of
      guanine-rich DNA strands of the fragile X chromosome repeats d(GGC)n, d(GCG)n and
      d(CGG)n, with n = 2, 4, 8 and 16. These strands are generally considered in the
      literature to form guanine tetraplexes responsible for the repeat expansion.
      However, we show in this paper that the repeats are reluctant to form
      tetraplexes. At physiological concentrations of either Na+ or K+ ions, the
      hexamers and dodecamers associate to form homoduplexes and the longer repeats
      generate homoduplexes and hairpins. The tetraplexes are rarely observed being
      relatively most stable with d(GGC)n and least stable with d(GCG)n. The
      tetraplexes are exclusively formed in the presence of K+ ions, at salt
      concentrations higher than physiological, more easily at higher than
      physiological temperatures, and they arise with extremely long kinetics (even
      days). Moreover, the capability to form tetraplexes sharply diminishes with the
      oligonucleotide length. These facts make the concept of the tetraplex appearance
      in this motif in vivo very improbable. Rather, a hairpin of the fragile X
      repeats, whose stability increases with the repeat length, is the probable
      structure responsible for the repeat expansion in genomes.

PMID- 14718552
TI  - PCR-based positive hybridization to detect genomic diversity associated with
      bacterial secondary metabolism.
AB  - A PCR-based positive hybridization (PPH) method was developed to explore toxic
      specific genes in common between toxigenic strains of Anabaena circinalis, a
      cyanobacterium able to produce saxitoxin (STX). The PPH technique is based on the
      same principles of suppression subtractive hybridization (SSH), although with the
      former no driver DNA is required and two tester genomic DNAs are hybridized at
      high stringency. The aim was to obtain genes associated with cyanobacterial STX
      production. The genetic diversity within phylogenetically similar strains of
      A.circinalis was investigated by comparing the results of the standard SSH
      protocol to the PPH approach by DNA-microarray analysis. SSH allowed the recovery
      of DNA libraries that were mainly specific for each of the two STX-producing
      strains used. Several candidate sequences were found by PPH to be in common
      between both the STX-producing testers. The PPH technique performed using
      unsubtracted genomic libraries proved to be a powerful tool to identify DNA
      sequences possibly transferred laterally between two cyanobacterial strains that
      may be candidate(s) in STX biosynthesis. The approach presented in this study
      represents a novel and valid tool to study the genetic basis for secondary
      metabolite production in microorganisms.

PMID- 14718551
TI  - YB-1 promotes strand separation in vitro of duplex DNA containing either
      mispaired bases or cisplatin modifications, exhibits endonucleolytic activities
      and binds several DNA repair proteins.
AB  - YB-1 is a multifunctional protein involved in the regulation of transcription,
      translation, mRNA splicing and probably DNA repair. It contains a conserved cold
      shock domain and it binds strongly to inverted CCAAT box of different promoters.
      In this study, we have found that purified YB-1 oligomerizes readily in solutions
      to form trimers, hexamers and oligomers of 12 molecules. The presence of ATP
      changed the conformation of YB-1 in such a way that only dimers were detected by
      gel filtration analyses. Purified YB-1 can separate different DNA duplexes
      containing blunt ends, 5' or 3' recessed ends, or forked structures. This strand
      separation activity is increased on cisplatin-modified DNA or with duplex
      molecules containing mismatches. In addition to its exonuclease activity, YB-1
      exhibits endonucleolytic activities in vitro. Finally, YB-1 affinity
      chromatography experiments have indicated that in addition to prespliceosome
      factors like nucleolin and ALY, YB-1 binds the DNA repair proteins MSH2, DNA
      polymerase delta, Ku80 and WRN proteins in vitro. Furthermore, immunofluorescence
      studies have shown that YB-1 re-localizes from the cytoplasm to nuclear areas
      containing either Ku80 or MSH2 proteins in human 293 embryonic kidney cells.
      These results suggest that YB-1 is involved in base excision and mismatch repair
      pathways.

PMID- 14718553
TI  - A novel assay to determine the sequence preference and affinity of DNA minor
      groove binding compounds.
AB  - Sequence-specific binding in the minor groove of DNA by small molecules is a
      growing area of research with possible therapeutic relevance. By selectively
      binding to DNA sequences required by critical transcription factors, these small
      molecules could potentially modulate the expression levels of disease-causing
      genes. Precise targeting of a critical transcription factor of a selected gene
      requires an understanding of the preferred sequence of the DNA binding compound.
      As new compounds are being synthesized, there is a need to evaluate their DNA
      recognition profile. We sought to establish a procedure to determine sequence
      preference of compounds with previously unknown binding properties. A novel
      procedure for determining the optimal DNA binding sequence of minor groove
      binding compounds is described here. The assay also allows for determination of
      the binding affinity to a particular sequence.

PMID- 14718554
TI  - Functionalization of poly(methyl methacrylate) (PMMA) as a substrate for DNA
      microarrays.
AB  - A chemical procedure was developed to functionalize poly(methyl methacrylate)
      (PMMA) substrates. PMMA is reacted with hexamethylene diamine to yield an
      aminated surface for immobilizing DNA in microarrays. The density of primary NH2
      groups was 0.29 nmol/cm2. The availability of these primary amines was confirmed
      by the immobilization of DNA probes and hybridization with a complementary DNA
      strand. The hybridization signal and the hybridization efficiency of the
      chemically aminated PMMA slides were comparable to the hybridization signal and
      the hybridization efficiency obtained from differently chemically modified PMMA
      slides, silanized glass, commercial silylated glass and commercial plastic Euray
      trade mark slides. Immobilized and hybridized densities of 10 and 0.75 pmol/cm2,
      respectively, were observed for microarrays on chemically aminated PMMA. The
      immobilized probes were heat stable since the hybridization performance of
      microarrays subjected to 20 PCR heat cycles was only reduced by 4%. In
      conclusion, this new strategy to modify PMMA provides a robust procedure to
      immobilize DNA, which is a very useful substrate for fabricating single use
      diagnostics devices with integrated functions, like sample preparation, treatment
      and detection using microfabrication and microelectronic techniques.

PMID- 14718555
TI  - Method to integrate multiple plasmids into the mycobacterial chromosome.
AB  - In order to create a system in which two independent plasmids can be integrated
      into a mycobacterial chromosome, a mycobacterial plasmid was constructed
      containing the phage attachment site attP from the mycobacteriophage L5 genome
      and additionally containing the bacterial attachment site, attB. This plasmid
      will integrate into the mycobacterial chromosome via recombination of the plasmid
      borne attP site with the chromosomal attB site in the presence of a mycobacterial
      vector carrying the L5 integrase (int) gene. The integrated plasmid has a plasmid
      borne attB site that is preserved and will accept the integration of additional
      mycobacterial plasmids containing the L5 attP site. This system should be useful
      in the construction of novel mycobacterial strains. In particular, this system
      provides a method by which several recombinant antigens or reporter constructs
      can be sequentially inserted into a mycobacterial strain and subsequently tested.

PMID- 14718556
TI  - Expression profiling of mammalian male meiosis and gametogenesis identifies novel
      candidate genes for roles in the regulation of fertility.
AB  - We report a comprehensive large-scale expression profiling analysis of mammalian
      male germ cells undergoing mitotic growth, meiosis, and gametogenesis by using
      high-density oligonucleotide microarrays and highly enriched cell populations.
      Among 11,955 rat loci investigated, 1268 were identified as differentially
      transcribed in germ cells at subsequent developmental stages compared with total
      testis, somatic Sertoli cells as well as brain and skeletal muscle controls. The
      loci were organized into four expression clusters that correspond to somatic,
      mitotic, meiotic, and postmeiotic cell types. This work provides information
      about expression patterns of approximately 200 genes known to be important during
      male germ cell development. Approximately 40 of those are included in a group of
      121 transcripts for which we report germ cell expression and lack of
      transcription in three somatic control cell types. Moreover, we demonstrate the
      testicular expression and transcriptional induction in mitotic, meiotic, and/or
      postmeiotic germ cells of 293 as yet uncharacterized transcripts, some of which
      are likely to encode factors involved in spermatogenesis and fertility. This
      group also contains potential germ cell-specific targets for innovative
      contraceptives. A graphical display of the data is conveniently accessible
      through the GermOnline database at http://www.germonline.org.

PMID- 14718557
TI  - The yeast elongator histone acetylase requires Sit4-dependent dephosphorylation
      for toxin-target capacity.
AB  - Kluyveromyces lactis zymocin, a heterotrimeric toxin complex, imposes a G1 cell
      cycle block on Saccharomyces cerevisiae that requires the toxin-target (TOT)
      function of holo-Elongator, a six-subunit histone acetylase. Here, we demonstrate
      that Elongator is a phospho-complex. Phosphorylation of its largest subunit Tot1
      (Elp1) is supported by Kti11, an Elongator-interactor essential for zymocin
      action. Tot1 dephosphorylation depends on the Sit4 phosphatase and its
      associators Sap185 and Sap190. Zymocin-resistant cells lacking or overproducing
      Elongator-associator Tot4 (Kti12), respectively, abolish or intensify Tot1
      phosphorylation. Excess Sit4.Sap190 antagonizes the latter scenario to reinstate
      zymocin sensitivity in multicopy TOT4 cells, suggesting physical competition
      between Sit4 and Tot4. Consistently, Sit4 and Tot4 mutually oppose Tot1 de
      /phosphorylation, which is dispensable for integrity of holo-Elongator but
      crucial for the TOT-dependent G1 block by zymocin. Moreover, Sit4, Tot4, and Tot1
      cofractionate, Sit4 is nucleocytoplasmically localized, and sit4Delta-nuclei
      retain Tot4. Together with the findings that sit4Delta and totDelta cells
      phenocopy protection against zymocin and the ceramide-induced G1 block, Sit4 is
      functionally linked to Elongator in cell cycle events targetable by antizymotics.

PMID- 14718558
TI  - Distinct functional domains within nucleoporins Nup153 and Nup98 mediate
      transcription-dependent mobility.
AB  - Despite the apparent overall structural stability of the nuclear pore complex
      during interphase, at least two nucleoporins have been shown to move dynamically
      on and off the pore. It is not yet certain what contribution nucleoporin mobility
      makes to the process of nuclear transport or how such mobility is regulated.
      Previously, we showed that Nup98 dynamically interacts with the NPC as well as
      bodies within the nucleus in a transcription-dependent manner. We have extended
      our studies of dynamics to include Nup153, another mobile nucleoporin implicated
      in RNA export. In both cases, we found that although only one domain is essential
      for NPC localization, other regions of the protein significantly affect the
      stability of association with the pore. Interestingly, like Nup98, the exchange
      of Nup153 on and off the pore is inhibited when transcription by Pol I and Pol II
      is blocked. We have mapped the regions required to link Nup98 and Nup153 mobility
      to transcription and found that the requirements differ depending on which
      polymerases are inhibited. Our data support a model whereby transcription of RNA
      is coupled to nucleoporin mobility, perhaps ultimately linking transport of RNAs
      to a cycle of remodeling at the nuclear pore basket.

PMID- 14718559
TI  - The transcriptome of prematurely aging yeast cells is similar to that of
      telomerase-deficient cells.
AB  - To help define the pathologies associated with yeast cells as they age, we
      analyzed the transcriptome of young and old cells isolated by elutriation, which
      allows isolation of biochemical quantities of old cells much further advanced in
      their life span than old cells prepared by the biotin-streptavidin method. Both
      18-generation-old wild-type yeast and 8-generation-old cells from a prematurely
      aging mutant (dna2-1), with a defect in DNA replication, were evaluated. Genes
      involved in gluconeogenesis, the glyoxylate cycle, lipid metabolism, and glycogen
      production are induced in old cells, signifying a shift toward energy storage. We
      observed a much more extensive generalized stress response known as the
      environmental stress response (ESR), than observed previously in biotin
      streptavidin-isolated cells, perhaps because the elutriated cells were further
      advanced in their life span. In addition, there was induction of DNA repair genes
      that fall in the so-called DNA damage "signature" set. In the dna2-1 mutant,
      energy production genes were also induced. The response in the dna2-1 strain is
      similar to the telomerase delete response, genes whose expression changes during
      cellular senescence in telomerase-deficient cells. We propose that these results
      suggest, albeit indirectly, that old cells are responding to genome instability.

PMID- 14718560
TI  - Two functionally identical modular enhancers in Drosophila troponin T gene
      establish the correct protein levels in different muscle types.
AB  - The control of muscle-specific expression is one of the principal mechanisms by
      which diversity is generated among muscle types. In an attempt to elucidate the
      regulatory mechanisms that control fiber diversity in any given muscle, we have
      focused our attention on the transcriptional regulation of the Drosophila
      Troponin T gene. Two, nonredundant, functionally identical, enhancer-like
      elements activate Troponin T transcription independently in all major muscles of
      the embryo and larvae as well as in adult somatic and visceral muscles. Here, we
      propose that the differential but concerted interaction of these two elements
      underlies the mechanism by which a particular muscle-type establish the correct
      levels of Troponin T expression, adapting these levels to their specific needs.
      This mechanism is not exclusive to the Troponin T gene, but is also relevant to
      the muscle-specific Troponin I gene. In conjunction with in vivo transgenic
      studies, an in silico analysis of the Troponin T enhancer-like sequences revealed
      that both these elements are organized in a modular manner. Extending this
      analysis to the Troponin I and Tropomyosin regulatory elements, the two other
      components of the muscle-regulatory complex, we have discovered a similar modular
      organization of phylogenetically conserved domains.

PMID- 14718561
TI  - The differential roles of budding yeast Tem1p, Cdc15p, and Bub2p protein dynamics
      in mitotic exit.
AB  - In the budding yeast Saccharomyces cerevisiae the mitotic spindle must be
      positioned along the mother-bud axis to activate the mitotic exit network (MEN)
      in anaphase. To examine MEN proteins during mitotic exit, we imaged the MEN
      activators Tem1p and Cdc15p and the MEN regulator Bub2p in vivo. Quantitative
      live cell fluorescence microscopy demonstrated the spindle pole body that
      segregated into the daughter cell (dSPB) signaled mitotic exit upon penetration
      into the bud. Activation of mitotic exit was associated with an increased
      abundance of Tem1p-GFP and the localization of Cdc15p-GFP on the dSPB. In
      contrast, Bub2p-GFP fluorescence intensity decreased in mid-to-late anaphase on
      the dSPB. Therefore, MEN protein localization fluctuates to switch from Bub2p
      inhibition of mitotic exit to Cdc15p activation of mitotic exit. The mechanism
      that elevates Tem1p-GFP abundance in anaphase is specific to dSPB penetration
      into the bud and Dhc1p and Lte1p promote Tem1p-GFP localization. Finally,
      fluorescence recovery after photobleaching (FRAP) measurements revealed Tem1p-GFP
      is dynamic at the dSPB in late anaphase. These data suggest spindle pole
      penetration into the bud activates mitotic exit, resulting in Tem1p and Cdc15p
      persistence at the dSPB to initiate the MEN signal cascade.

PMID- 14718562
TI  - Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II
      receptor endocytosis.
AB  - Phospholipase D (PLD) is a key facilitator of multiple types of membrane vesicle
      trafficking events. Two PLD isoforms, PLD1 and PLD2, exist in mammals. Initial
      studies based on overexpression studies suggested that in resting cells, human
      PLD1 localized primarily to the Golgi and perinuclear vesicles in multiple cell
      types. In contrast, overexpressed mouse PLD2 was observed to localize primarily
      to the plasma membrane, although internalization on membrane vesicles was
      observed subsequent to serum stimulation. A recent report has suggested that the
      assignment of PLD2 to the plasma membrane is in error, because the endogenous
      isoform in rat secretory cells was imaged and found to be present primarily in
      the Golgi apparatus. We have reexamined this issue by using a monoclonal antibody
      specific for mouse PLD2, and find, as reported initially using overexpression
      studies, that endogenous mouse PLD2 is detected most readily at the plasma
      membrane in multiple cell types. In addition, we report that mouse, rat, and
      human PLD2 when overexpressed all similarly localize to the plasma membrane in
      cell lines from all three species. Finally, studies conducted using
      overexpression of wild-type active or dominant-negative isoforms of PLD2 and RNA
      interference-mediated targeting of PLD2 suggest that PLD2 functions at the plasma
      membrane to facilitate endocytosis of the angiotensin II type 1 receptor.

PMID- 14718563
TI  - Transcription of Drosophila troponin I gene is regulated by two conserved,
      functionally identical, synergistic elements.
AB  - The Drosophila wings-up A gene encodes Troponin I. Two regions, located upstream
      of the transcription initiation site (upstream regulatory element) and in the
      first intron (intron regulatory element), regulate gene expression in specific
      developmental and muscle type domains. Based on LacZ reporter expression in
      transgenic lines, upstream regulatory element and intron regulatory element yield
      identical expression patterns. Both elements are required for full expression
      levels in vivo as indicated by quantitative reverse transcription-polymerase
      chain reaction assays. Three myocyte enhancer factor-2 binding sites have been
      functionally characterized in each regulatory element. Using exon specific
      probes, we show that transvection is based on transcriptional changes in the
      homologous chromosome and that Zeste and Suppressor of Zeste 3 gene products act
      as repressors for wings-up A. Critical regions for transvection and for Zeste
      effects are defined near the transcription initiation site. After in silico
      analysis in insects (Anopheles and Drosophila pseudoobscura) and vertebrates
      (Ratus and Coturnix), the regulatory organization of Drosophila seems to be
      conserved. Troponin I (TnI) is expressed before muscle progenitors begin to fuse,
      and sarcomere morphogenesis is affected by TnI depletion as Z discs fail to form,
      revealing a novel developmental role for the protein or its transcripts. Also,
      abnormal stoichiometry among TnI isoforms, rather than their absolute levels,
      seems to cause the functional muscle defects.

PMID- 14718564
TI  - Adenylyl cyclase G is activated by an intramolecular osmosensor.
AB  - Adenylyl cyclase G (ACG) is activated by high osmolality and mediates inhibition
      of spore germination by this stress factor. The catalytic domains of all
      eukaryote cyclases are active as dimers and dimerization often mediates
      activation. To investigate the role of dimerization in ACG activation, we
      coexpressed ACG with an ACG construct that lacked the catalytic domain
      (ACGDeltacat) and was driven by a UV-inducible promoter. After UV induction of
      ACGDeltacat, cAMP production by ACG was strongly inhibited, but osmostimulation
      was not reduced. Size fractionation of native ACG showed that dimers were formed
      between ACG molecules and between ACG and ACGDeltacat. However, high osmolality
      did not alter the dimer/monomer ratio. This indicates that ACG activity requires
      dimerization via a region outside the catalytic domain but that dimer formation
      does not mediate activation by high osmolality. To establish whether ACG required
      auxiliary sensors for osmostimulation, we expressed ACG cDNA in a yeast adenylyl
      cyclase null mutant. In yeast, cAMP production by ACG was similarly activated by
      high osmolality as in Dictyostelium. This strongly suggests that the ACG
      osmosensor is intramolecular, which would define ACG as the first characterized
      primary osmosensor in eukaryotes.

PMID- 14718565
TI  - Loss of PALS1 expression leads to tight junction and polarity defects.
AB  - Prior work in our laboratory established a connection between the PALS1/PATJ/CRB3
      and Par6/Par3/aPKC protein complexes at the tight junction of mammalian
      epithelial cells. Utilizing a stable small interfering RNA expression system, we
      have markedly reduced expression of the tight junction-associated protein PALS1
      in MDCKII cells. The loss of PALS1 resulted in a corresponding loss of expression
      of PATJ, a known binding partner of PALS1, but had no effect on the expression of
      CRB3. However, the absence of PALS1 and PATJ expression did result in the
      decreased association of CRB3 with members of the Par6/Par3/aPKC protein complex.
      The consequences of the loss of PALS1 and PATJ were exhibited by a delay in the
      polarization of MDCKII monolayers after calcium switch, a decrease in the
      transepithelial electrical resistance, and by the inability of these cells to
      form lumenal cysts when grown in a collagen gel matrix. These defects in polarity
      determination may be the result of the lack of recruitment of aPKC to the tight
      junction in PALS1-deficient cells, as observed by confocal microscopy, and
      subsequent alterations in downstream signaling events.

PMID- 14718566
TI  - TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity,
      spindle pole organization, and bipolar spindle assembly.
AB  - The XMAP215/Dis1 MAP family is thought to regulate microtubule plus-end assembly
      in part by antagonizing the catastrophe-promoting function of kin I kinesins, yet
      XMAP215/Dis1 proteins localize to centrosomes. We probed the mitotic function of
      TOGp (human homolog of XMAP215/Dis1) using siRNA. Cells lacking TOGp assembled
      multipolar spindles, confirming results of Gergely et al. (2003. Genes Dev. 17,
      336-341). Eg5 motor activity was necessary to maintain the multipolar morphology.
      Depletion of TOGp decreased microtubule length and density in the spindle by
      approximately 20%. Depletion of MCAK, a kin I kinesin, increased MT lengths and
      density by approximately 20%, but did not disrupt spindle morphology. Mitotic
      cells lacking both TOGp and MCAK formed bipolar and monopolar spindles,
      indicating that TOGp and MCAK contribute to spindle bipolarity, without major
      effects on MT stability. TOGp localized to centrosomes in the absence of MTs and
      depletion of TOGp resulted in centrosome fragmentation. TOGp depletion also
      disrupted MT minus-end focus at the spindle poles, detected by localizations of
      NuMA and the p150 component of dynactin. The major functions of TOGp during
      mitosis are to focus MT minus ends at spindle poles, maintain centrosome
      integrity, and contribute to spindle bipolarity.

PMID- 14718567
TI  - Fibronectin matrix assembly regulates alpha5beta1-mediated cell cohesion.
AB  - Integrin-extracellular matrix (ECM) interactions in two-dimensional (2D) culture
      systems are widely studied (Goldstein and DiMilla, 2002. J Biomed. Mater. Res.
      59, 665-675; Koo et al., 2002. J. Cell Sci. 115, 1423-1433). Less understood is
      the role of the ECM in promoting intercellular cohesion in three-dimensional (3D)
      environments. We have demonstrated that the alpha5beta1-integrin mediates strong
      intercellular cohesion of 3D cellular aggregates (Robinson et al., 2003. J. Cell
      Sci. 116, 377-386). To further investigate the mechanism of alpha5beta1-mediated
      cohesivity, we used a series of chimeric alpha5beta1-integrin-expressing cells
      cultured as multilayer cellular aggregates. In these cell lines, the alpha5
      subunit cytoplasmic domain distal to the GFFKR sequence was truncated, replaced
      with that of the integrin alpha4, the integrin alpha2, or maintained intact.
      Using these cells, alpha5beta1-integrin-mediated cell aggregation, compaction and
      cohesion were determined and correlated with FN matrix assembly. The data
      presented demonstrate that cells cultured in the absence of external mechanical
      support can assemble a FN matrix that promotes integrin-mediated aggregate
      compaction and cohesion. Further, inhibition of FN matrix assembly blocks the
      intercellular associations required for compaction, resulting in cell dispersal.
      These results demonstrate that FN matrix assembly contributes significantly to
      tissue cohesion and represents an alternative mechanism for regulating tissue
      architecture.

PMID- 14718568
TI  - TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the
      meiotic recombination checkpoint.
AB  - Mammalian TopBP1 is a BRCT domain-containing protein whose function in mitotic
      cells is linked to replication and DNA damage checkpoint. Here, we study its
      possible role during meiosis in mice. TopBP1 foci are abundant during early
      prophase I and localize mainly to histone gamma-H2AX-positive domains, where DNA
      double-strand breaks (required to initiate recombination) occur. Strikingly,
      TopBP1 showed a pattern almost identical to that of ATR, a PI3K-like kinase
      involved in mitotic DNA damage checkpoint. In the synapsis-defective Fkbp6(-/-)
      mouse, TopBP1 heavily stains unsynapsed regions of chromosomes. We also tested
      whether Schizosaccharomyces pombe Cut5 (the TopBP1 homologue) plays a role in the
      meiotic recombination checkpoint, like spRad3, the ATR homologue. Indeed, we
      found that a cut5 mutation suppresses the checkpoint-dependent meiotic delay of a
      meiotic recombination defective mutant, indicating a direct role of the Cut5
      protein in the meiotic checkpoint. Our findings suggest that ATR and TopBP1
      monitor meiotic recombination and are required for activation of the meiotic
      recombination checkpoint.

PMID- 14718569
TI  - Cardiac steroids induce changes in recycling of the plasma membrane in human NT2
      cells.
AB  - Cardiac steroids (CSs) are specific inhibitors of Na+, K(+)-ATPase activity.
      Although the presence of CS-like compounds in animal tissues has been
      established, their physiological role is not evident. In the present study,
      treatment of human NT2 cells with physiological concentrations (nanomolar) of CSs
      caused the accumulation of large vesicles adjacent to the nucleus. Experiments
      using N-(3-triethylammonium propyl)-4-(dibutilamino)styryl-pyrodinum dibromide,
      transferrin, low-density lipoprotein, and selected anti-transferrin receptor and
      Rab protein antibodies revealed that CSs induced changes in endocytosis-dependent
      membrane traffic. Our data indicate that the CS-induced accumulation of
      cytoplasmic membrane components is a result of inhibited recycling within the
      late endocytic pathway. Furthermore, our results support the notion that the CS
      induced changes in membrane traffic is mediated by the Na+, K(+)-ATPase. These
      phenomena were apparent in NT2 cells at nanomolar concentrations of CSs and were
      observed also in other human cell lines, pointing to the generality of this
      phenomenon. Based on these observations, we propose that the endogenous CS-like
      compounds are physiological regulators of recycling of endocytosed membrane
      proteins and cargo.

PMID- 14718570
TI  - Activation of EGF receptor kinase by L1-mediated homophilic cell interactions.
AB  - Neural cell adhesion molecules (CAMs) are important players during neurogenesis
      and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of
      these developmental processes entail the activation of cellular signaling
      cascades. Pharmacological and genetic evidence indicates that the neurite
      outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the
      stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF
      receptors. It has long been suspected that neural CAMs might physically interact
      with RTKs, but their activation by specific cell adhesion events has not been
      directly demonstrated. Here we report that gain-of-function conditions of the
      Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding
      defects in the developing Drosophila wing. This phenotype can be suppressed by
      decreasing the normal gene dosage of the Drosophila EGF receptor gene.
      Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM
      results in the specific activation of human EGF tyrosine kinase at cell contact
      sites and EGF receptors engage in a physical interaction with L1-CAM molecules.
      Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF
      receptor signaling in vitro and in vivo.

PMID- 14718571
TI  - A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease
      cells.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is typified by the
      accumulation of fluid-filled cysts and abnormalities in renal epithelial cell
      function. The disease is principally caused by mutations in the gene encoding
      polycystin-1, a large basolateral plasma membrane protein expressed in kidney
      epithelial cells. Our studies reveal that, in normal kidney cells, polycystin-1
      forms a complex with the adherens junction protein E-cadherin and its associated
      catenins, suggesting a role in cell adhesion or polarity. In primary cells from
      ADPKD patients, the polycystin-1/polycystin-2/E-cadherin/beta-catenin complex was
      disrupted and both polycystin-1 and E-cadherin were depleted from the plasma
      membrane as a result of the increased phosphorylation of polycystin-1. The loss
      of E-cadherin was compensated by the transcriptional upregulation of the normally
      mesenchymal N-cadherin. Increased cell surface N-cadherin in the disease cells in
      turn stabilized the continued plasma membrane localization of beta-catenin in the
      absence of E-cadherin. The results suggest that enhanced phosphorylation of
      polycystin-1 in ADPKD cells precipitates changes in its localization and its
      ability to form protein complexes that are critical for the stabilization of
      adherens junctions and the maintenance of a fully differentiated polarized renal
      epithelium.

PMID- 14718572
TI  - CRB3 binds directly to Par6 and regulates the morphogenesis of the tight
      junctions in mammalian epithelial cells.
AB  - Crumbs is an apical transmembrane protein crucial for epithelial morphogenesis in
      Drosophila melanogaster embryos. A protein with all the characteristics for a
      Crumbs homologue has been identified from patients suffering from retinitis
      pigmentosa group 12, but this protein (CRB1) is only expressed in retina and some
      parts of the brain, both in human and mouse. Here, we describe CRB3, another
      Crumbs homologue that is preferentially expressed in epithelial tissues and
      skeletal muscles in human. CRB3 shares the conserved cytoplasmic domain with
      other Crumbs but exhibits a very short extracellular domain without the EGF- and
      laminin A-like G repeats present in the other Crumbs. CRB3 is localized to the
      apical and subapical area of epithelial cells from the mouse and human intestine,
      suggesting that it could play a role in epithelial morphogenesis. Indeed,
      expression of CRB3 or of a chimera containing the extracellular domain of the
      neurotrophin receptor p75NTR and the transmembrane and cytoplasmic domains of
      CRB3 led to a slower development of functional tight junctions in Madin-Darby
      canine kidney cells. This phenotype relied on the presence of CRB3 four last
      amino acids (ERLI) that are involved in a direct interaction with Par6, a
      regulator of epithelial polarity and tight junction formation. Thus, CRB3,
      through its cytoplasmic domain and its interactors, plays a role in apical
      membrane morphogenesis and tight junction regulation.

PMID- 14718573
TI  - Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased
      susceptibility to apoptosis-like cell death on exposure to NaCl stress.
AB  - Yeast cells deleted for the SRO7/SOP1 encoded tumor suppressor homologue show
      increased sensitivity to NaCl stress. On exposure to growth-inhibiting NaCl
      concentrations, sro7Delta mutants display a rapid loss in viability that is
      associated with markers of apoptosis: accumulation of reactive oxygen species,
      DNA breakage, and nuclear fragmentation. Additional deletion of the yeast
      metacaspase gene YCA1 prevents the primary fast drop in viability and diminishes
      nuclear fragmentation and DNA breakage. We also observed that NaCl induced loss
      in viability of wild-type cells is Yca1p dependent. However, a yeast strain
      deleted for both SRO7 and its homologue SRO77 exhibits NaCl-induced cell death
      that is independent on YCA1. Likewise, sro77Delta single mutants do not survive
      better after additional deletion of the YCA1 gene, and both sro77Delta and
      sro77Deltayca1Delta mutants display apoptotic characteristics when exposed to
      growth-inhibiting salinity, suggesting that yeast possesses Yca1p-independent
      pathway(s) for apoptosis-like cell death. The activity of Yca1p increases with
      increasing NaCl stress and sro7Delta mutants achieve levels that are higher than
      in wild-type cells. However, mutants lacking SRO77 do not enhance caspase
      activity when subject to NaCl stress, suggesting that Sro7p and Sro77p exert
      opposing effects on the cellular activity of Yca1p.

PMID- 14718574
TI  - The human plasma proteome: a nonredundant list developed by combination of four
      separate sources.
AB  - We have merged four different views of the human plasma proteome, based on
      different methodologies, into a single nonredundant list of 1175 distinct gene
      products. The methodologies used were 1) literature search for proteins reported
      to occur in plasma or serum; 2) multidimensional chromatography of proteins
      followed by two-dimensional electrophoresis and mass spectroscopy (MS)
      identification of resolved proteins; 3) tryptic digestion and multidimensional
      chromatography of peptides followed by MS identification; and 4) tryptic
      digestion and multidimensional chromatography of peptides from low-molecular-mass
      plasma components followed by MS identification. Of 1,175 nonredundant gene
      products, 195 were included in more than one of the four input datasets. Only 46
      appeared in all four. Predictions of signal sequence and transmembrane domain
      occurrence, as well as Genome Ontology annotation assignments, allowed
      characterization of the nonredundant list and comparison of the data sources. The
      "nonproteomic" literature (468 input proteins) is strongly biased toward signal
      sequence-containing extracellular proteins, while the three proteomics methods
      showed a much higher representation of cellular proteins, including nuclear,
      cytoplasmic, and kinesin complex proteins. Cytokines and protein hormones were
      almost completely absent from the proteomics data (presumably due to low
      abundance), while categories like DNA-binding proteins were almost entirely
      absent from the literature data (perhaps unexpected and therefore not sought).
      Most major categories of proteins in the human proteome are represented in
      plasma, with the distribution at successively deeper layers shifting from mostly
      extracellular to a distribution more like the whole (primarily cellular)
      proteome. The resulting nonredundant list confirms the presence of a number of
      interesting candidate marker proteins in plasma and serum.

PMID- 14718575
TI  - Immunoproteomics: Mass spectrometry-based methods to study the targets of the
      immune response.
AB  - The mammalian immune system has evolved to display fragments of protein antigens
      derived from microbial pathogens to immune effector cells. These fragments are
      typically peptides liberated from the intact antigens through distinct
      proteolytic mechanisms that are subsequently transported to the cell surface
      bound to chaperone-like receptors known as major histocompatibility complex (MHC)
      molecules. These complexes are then scrutinized by effector T cells that express
      clonally distributed T cell receptors with specificity for specific MHC-peptide
      complexes. In normal uninfected cells, this process of antigen processing and
      presentation occurs continuously, with the resultant array of self-antigen
      derived peptides displayed on the surface of these cells. Changes in this peptide
      landscape of cells act to alert immune effector cells to changes in the
      intracellular environment that may be associated with infection, malignant
      transformation, or other abnormal cellular processes, resulting in a cascade of
      events that result in their elimination. Because peptides play such a crucial
      role in informing the immune system of infection with viral or microbial
      pathogens and the transformation of cells in malignancy, the tools of proteomics,
      in particular mass spectrometry, are ideally suited to study these immune
      responses at a molecular level. Here we review recent advances in the studies of
      immune responses that have utilized mass spectrometry and associated
      technologies, with specific examples from collaboration between our laboratories.

PMID- 14718577
TI  - Inverse agonist activity of selected ligands of the cysteinyl-leukotriene
      receptor 1.
AB  - Cysteinyl leukotrienes (CysLTs) are associated with several inflammatory
      processes, including asthma. Due to this association, considerable effort has
      been invested in the development of antagonists to the CysLT receptors
      (CysLT(1)R). Many of these molecules have been shown to specifically interact
      with CysLT(1)R, but little is known about their impact on the conformation of the
      receptor and its activity. We were especially interested in possible inverse
      agonist activity of the antagonists. Using a constitutively active mutant (N106A)
      of the human CysLT(1)R and the wild-type (WT) receptor coexpressed with the
      G(alphaq) subunit of the trimeric G protein, we were able to address this issue
      with ligands commonly used in therapy. We demonstrated that some of these
      molecules are inverse agonists, whereas others act as partial agonists. In cells
      expressing the CysLT(1)R mutant N106A exposed to Montelukast, Zafirlukast, or 3
      [[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), the basal
      inositol phosphate production was reduced by 53 +/- 6, 44 +/- 3, and 54 +/- 4%,
      respectively. On the other hand, 6(R)-(4-carboxyphenylthio)-5(S)-hydroxy
      7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid (BayU9773) and 1-[2-hydroxy-3-propyl
      4-[4-(1H-tetrazole-5-YL)-butoxy]-phenyl ethanone] (LY171883) acted as partial
      agonists and alpha-pentyl-3-[2-quinolinylmethoxy] benzyl alcohol (REV 5901) as a
      neutral antagonist. However, in cells expressing CysLT(1)R and G(alphaq), all
      antagonists used had inverse agonist activity. The decrease in basal inositol
      phosphate production by ligands with inverse agonist activity could be inhibited
      by a more neutral antagonist, confirming the specificity of the reaction. We
      demonstrate here that Montelukast, MK571, and Zafirlukast can act as inverse
      agonists on the human CysLT(1) receptor.

PMID- 14718578
TI  - Role of neuronal KATP channels and extraneuronal monoamine transporter on
      norepinephrine overflow in a model of myocardial low flow ischemia.
AB  - Global myocardial low flow ischemia results in an uniform suppression of
      norepinephrine (NE) overflow from the heart. We hypothesized that opening of
      neuronal ATP-sensitive potassium (K(ATP)) channels as well as activation of the
      extraneuronal monoamine transporter (EMT) mediates attenuation of NE overflow
      during low flow ischemia. Isolated rat hearts were subjected to low coronary flow
      of 0.4 ml min(-1). Release of endogenous NE was induced by electrical field
      stimulation. EMT activity was measured as the transport rate of the substrate N
      [methyl-3H]4-phenylpyridinium ([3H]MPP+). NE overflow decreased by 57 +/- 2%
      within 120 min of low flow. Five minutes of reperfusion at normal flow (8 ml min(
      1)) restored NE overflow to baseline. K(ATP) channel blockade with glibenclamide
      as well as EMT blockade with corticosterone increased NE overflow 1.5- and 2-fold
      at 120 min of low flow, whereas neither drug affected NE overflow in the absence
      of flow reduction. At normal flow, K(ATP) channel opening with cromakalim
      suppressed NE overflow, both in the presence and absence of EMT blockade (14 +/-
      4 and 9 +/- 1%). However, cromakalim had no effect on EMT activity as indicated
      by an unaffected [3H]MPP+ overflow. In conclusion, activation of both K(ATP)
      channels and EMT mediate suppression of NE overflow during low flow ischemia.
      K(ATP) channels impair NE release directly at presynaptic nerve endings, whereas
      EMT increases NE elimination in a manner independent of K(ATP) channels.

PMID- 14718579
TI  - Effects of SanOrg123781A, a synthetic hexadecasaccharide, in a mouse model of
      electrically induced carotid artery injury: synergism with the antiplatelet agent
      clopidogrel.
AB  - SanOrg123781A is a synthetic hexadecasaccharide that displays antithrombin
      dependent inhibition of factor Xa and thrombin and potent antithrombotic effects.
      The antithrombotic activity of SanOrg123781A has been studied in a new mouse
      model of arterial thrombosis, where thrombus formation was induced by the
      application of an electrical current to the adventitial surface of a carotid
      artery. In this model, antiplatelet agents such as the ADP-receptor antagonist
      clopidogrel (30 mg/kg, p.o. 2 h before stimulation) and the GpIIb/IIIa antagonist
      SR121566A [3-(N-[4-(4-[amino(imino)methyl]phenyl)-1,3-thiazol-2-yl]-N-[1
      (carboxymethyl)piperidin-4-yl]amino)propionic acid, trihydrochloride] (0.3 mg/kg,
      i.v. 5 min before stimulation) strongly prolonged the time to occlusion (TTO)
      (761 and 473% increases, respectively), whereas aspirin was devoid of
      antithrombotic activity. Standard heparin (2 mg/kg, i.v.), the low molecular
      weight heparin enoxaparin (20 mg/kg, i.v.), and the synthetic, antithrombin
      dependent inhibitor of factor Xa fondaparinux (10 mg/kg, i.v.) were also active
      in this model (742, 707, and 602% TTO increases, respectively). Interestingly,
      SanOrg123781A was active at much lower doses than the other oligosaccharides
      (554% increase in TTO at 0.3 mg/kg, i.v. 5 min before stimulation). Low doses of
      SanOrg123781A administered in combination with low doses of clopidogrel led to a
      marked increase in TTO, which was statistically more important than the additive
      effects of the two compounds given alone. These results indicate that
      SanOrg123781A exerts a potent antithrombotic activity in a mouse model of
      arterial thrombosis when compared with reference compounds and show that the
      combination of SanOrg123781A with clopidogrel leads to a marked synergistic
      antithrombotic effect.

PMID- 14718580
TI  - Novel 2',6'-dimethyl-L-tyrosine-containing pyrazinone opioid mimetic mu-agonists
      with potent antinociceptive activity in mice.
AB  - Novel bioactive opioid mimetic agonists containing 2',6'-dimethyl-l-tyrosine
      (Dmt) and a pyrazinone ring interact with mu- and delta-opioid receptors.
      Compound 1 [3-(4' -Dmt-aminobutyl)-6-(3'-Dmt-aminopropyl)-5-methyl
      2(1H)pyrazinone] exhibited high mu-opioid receptor affinity and selectivity
      (K(i)mu = 0.021 nM and K(i)delta/K(i)mu = 1,519, respectively), and agonist
      activity on guinea pig ileum (IC(50) = 1.7 nM) with weaker delta-bioactivity on
      mouse vas deferens (IC(50) = 25.8 nM). Other compounds (2-4) had mu-opioid
      receptor affinities and selectivities 2- to 5-fold and 4- to 7-fold less than 1,
      respectively. Intracerebroventricular administration of 1 in mice exhibited
      potent naloxone reversible antinociception (65 to 71 times greater than morphine)
      in both tail-flick (TF) and hot-plate (HP) tests. Distinct opioid antagonists had
      differential effects on antinociception: naltrindole (delta-antagonist) partially
      blocked antinociception in the TF, but it was ineffective in the HP test, whereas
      beta-funaltrexamine (irreversible antagonist, mu(1)/mu(2)-subtypes) but not
      naloxonazine (mu(1)-subtype) inhibited TF test antinociception, yet both blocked
      antinociception in the HP test. Our data indicated that 1 acted through mu- and
      delta-opioid receptors to produce spinal antinociception, although primarily
      through the mu(2)-receptor subtype; however, the mu(1)-receptor subtype dominates
      supraspinally. Subcutaneous and oral administration indicated that 1 crossed
      gastrointestinal and blood-brain barriers to produce central nervous system
      mediated antinociception. Furthermore, daily s.c. dosing of mice with 1 for 1
      week developed tolerance in a similar manner to that of morphine in TF and HP
      tests, implicating that 1 also acts through a similar mechanism analogous to
      morphine at mu-opioid receptors.

PMID- 14718581
TI  - Neutral and anionic liposome-encapsulated hemoglobin: effect of postinserted
      poly(ethylene glycol)-distearoylphosphatidylethanolamine on distribution and
      circulation kinetics.
AB  - To prepare long-circulating liposomes, poly(ethylene glycol) (PEG)-lipid is
      usually mixed with other lipid components before vesicle formation. PEG-lipids
      can also be postinserted in the outer layer of liposomes after the preparation.
      In this study, PEG-distearoylphosphatidylethanolamine was incorporated by
      postinsertion technique into liposome-encapsulated hemoglobin (LEH) carrying
      neutral or negative charge. Postinsertion technique improved the encapsulation
      efficiency of hemoglobin from about 0.0017 to 0.017 (hemoglobin/phospholipid,
      molar ratio) for a similar lipid composition. Thus, neutral, anionic, PEG
      neutral, and PEG-anionic LEHs were made and labeled with technetium-99m to follow
      their biodistribution. A small dose of LEH (approximately 15 mg of phospholipid)
      was injected intravenously in rabbits, and its distribution was monitored by
      blood sampling, gamma camera imaging, and tissue radioactivity counting on
      necropsy. The 24-h blood levels of neutral, PEG-neutral, anionic, and PEG-anionic
      LEHs were 14, 40.3, 13.1, and 35.7% of injected dose, respectively; calculated
      T(1/2) values of circulation were 8.9, 19.3, 9.6, and 16.5 h, respectively.
      PEGylation also influenced accumulation of LEH in the reticuloendothelial system.
      Liver uptake of neutral LEH dropped from 52.1 to 19.1%, whereas that of anionic
      LEH came down from 35.3 to 11.5% on PEGylation. In contrast, PEGylation increased
      the spleen uptake by 8.5- and 2.5-fold for neutral and anionic LEH, respectively.
      The results demonstrate that PEGylation by postinsertion not only improves the
      circulation t1/2 of LEH but also enhances hemoglobin content inside the vesicles
      for better oxygen-carrying capacity.

PMID- 14718582
TI  - Polyphenolic antioxidants mimic the effects of 1,4-dihydropyridines on
      neurotensin receptor function in PC3 cells.
AB  - This study aimed to determine the mechanism(s) by which 1,4-dihydropyridine Ca2+
      channel blockers (DHPs) enhance the binding of neurotensin (NT) to prostate
      cancer PC3 cells and inhibit NT-induced inositol phosphate formation. Earlier
      work indicated that these effects, which involved the G protein-coupled NT
      receptor NTR1, were indirect and required cellular metabolism or architecture. At
      the micromolar concentrations used, DHPs can block voltage-sensitive and store
      operated Ca2+ channels, K+ channels, and Na+ channels, and can inhibit lipid
      peroxidation. By varying [Ca2+] and testing the effects of stimulators and
      inhibitors of Ca2+ influx and internal Ca2+ release, we determined that although
      DHPs may have inhibited inositol phosphate formation partly by blocking Ca2+
      influx, the effect on NT binding was Ca2+-independent. By varying [K+] and [Na+],
      we showed that these ions did not contribute to either effect. For a series of
      DHPs, the activity order for effects on NTR1 function followed that for
      antioxidant ability. Antioxidant polyphenols (luteolin and resveratrol) mimicked
      the effects of DHPs and showed structural similarity to DHPs. Antioxidants with
      equal redox ability, but without structural similarity to DHPs (such as alpha
      tocopherol, riboflavin, and N-acetyl-cysteine) were without effect. A
      flavoprotein oxidase inhibitor (diphenylene iodonium) and a hydroxy radical
      scavenger (butylated hydroxy anisole) also displayed the effects of DHPs. In
      conclusion, DHPs indirectly alter NTR1 function in live cells by a mechanism that
      depends on the drug's ability to donate hydrogen but does not simply involve
      sulfhydryl reduction.

PMID- 14718583
TI  - The N terminus of the human alpha1D-adrenergic receptor prevents cell surface
      expression.
AB  - We previously reported that truncation of the N-terminal 79 amino acids of
      alpha(1D)-adrenoceptors (Delta(1-79)alpha(1D)-ARs) greatly increases binding site
      density. In this study, we determined whether this effect was associated with
      changes in alpha(1D)-AR subcellular localization. Confocal imaging of green
      fluorescent protein (GFP)-tagged receptors and sucrose density gradient
      fractionation suggested that full-length alpha(1D)-ARs were found primarily in
      intracellular compartments, whereas Delta(1-79)alpha(1D)-ARs were translocated to
      the plasma membrane. This resulted in a 3- to 4-fold increase in intrinsic
      activity for stimulation of inositol phosphate formation by norepinephrine. We
      determined whether this effect was transplantable by creating N-terminal chimeras
      of alpha(1)-ARs containing the body of one subtype and the N terminus of another
      (alpha(1A)NT-D, alpha(1B)NT-D, alpha(1D)NT-A, and alpha(1D)NT-B). When expressed
      in human embryonic kidney 293 cells, radioligand binding revealed that binding
      densities of alpha(1A)-or alpha(1B)-ARs containing the alpha(1D)-N terminus
      decreased by 86 to 93%, whereas substitution of alpha(1A)- or alpha(1B)-N termini
      increased alpha(1D)-AR binding site density by 2- to 3-fold. Confocal microscopy
      showed that GFP-tagged alpha(1D)NT-B-ARs were found only on the cell surface,
      whereas GFP-tagged alpha(1B)NT-D-ARs were completely intracellular. Radioligand
      binding and confocal imaging of GFP-tagged alpha(1D)- and Delta(1-79)alpha(1D)
      ARs expressed in rat aortic smooth muscle cells produced similar results,
      suggesting these effects are generalizable to cell types that endogenously
      express alpha(1D)-ARs. These findings demonstrate that the N-terminal region of
      alpha(1D)-ARs contain a transplantable signal that is critical for regulating
      formation of functional bindings, through regulating cellular localization.

PMID- 14718584
TI  - Loss of peripheral morphine analgesia contributes to the reduced effectiveness of
      systemic morphine in neuropathic pain.
AB  - It is well known that the analgesic potency of morphine is reduced in neuropathic
      pain. In this study, we demonstrate that the decreased effectiveness of systemic
      morphine in neuropathic pain might be caused by the loss of morphine analgesia at
      the periphery. When given s.c. or i.t., the dose-response curves for morphine
      analgesia in Hargreaves thermal test were shifted rightward in partial sciatic
      nerve-injured mice compared with control sham-operated mice. The dose-response
      curves for i.c.v. morphine analgesia, however, were unchanged in nerve-injured
      mice, indicating no decrease in morphine potency at the supraspinal level. On the
      other hand, the dose-dependent analgesia produced by intraplantar (i.pl.)
      morphine in sham-operated mice almost completely disappeared in nerve-injured
      mice. With the more sensitive algogenic-induced nociceptive flexion test,
      significant reduction in the analgesic potency of systemic morphine was observed
      for bradykinin (BK) nociception in nerve-injured mice, and the analgesic effect
      of i.pl. morphine against BK nociception in sham-operated mice disappeared in
      nerve-injured mice. In immunohistochemical experiments, we found that, under
      normal state, mu-opioid receptors (MOPs) were mainly expressed in small-diameter
      unmyelinated dorsal root ganglion (DRG) neurons and colocalized with bradykinin
      B2 receptors. When we examined MOP expression in the DRG of nerve-injured mice,
      we observed a drastic decrease in MOP expression. Altogether, these data suggest
      that the lower potency of systemic morphine in neuropathic pain could be at least
      partly caused by the decreased MOP expression in DRG and subsequent loss of
      peripheral morphine analgesia in such a condition.

PMID- 14718585
TI  - Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma
      in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2
      (3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H
      dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575).
AB  - A previous study by us suggests the utility of cerebrospinal fluid (CSF) and
      plasma Abeta as biomarkers of beta- or gamma-secretase inhibition. The present
      study characterized further Abeta pharmacodynamics in these tissues from Tg2576
      mice and examined their correlation with brain Abeta after acute treatment with a
      potent gamma-secretase inhibitor, N(2)-[(2S)-2-(3,5-difluorophenyl)-2
      hydroxyethanoyl]-N(1)-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7
      yl]-l-alaninamide (LY-411575). A single dose of LY-411575 dose-dependently (0.1
      10 mg/kg p.o.) reduced Abeta(1-40) and Abeta(1-42) in the CSF and the brain. In
      contrast, plasma Abeta levels were increased by 0.1 mg/kg LY-411575 and were
      followed by a dose-dependent reduction at higher doses. The time courses of Abeta
      reduction and recovery were distinct for the three tissues: maximal declines in
      Abeta levels were evident by 3 h in the CSF and plasma but not until 9 h in the
      brain. A recovery in Abeta levels was underway in the CSF by 9 h and nearly
      completed by 24 h in all tissues. The differential time courses in the three
      compartments do not seem to be due to pharmacokinetic factors. Five days of twice
      daily treatment with LY-411575 not only sustained the Abeta reductions in all
      tissues but also significantly augmented the efficacy in the brain and plasma.
      The increased efficacy occurred in the absence of compound accumulation and was
      consistent with the recovery rates in each compartment. Overall, Abeta in the CSF
      and not plasma seems to be a better biomarker of brain Abeta reduction; however,
      the time course of Abeta changes needs to be established in clinical studies.

PMID- 14718586
TI  - Histogranin-like antinociceptive and anti-inflammatory derivatives of o
      phenylenediamine and benzimidazole.
AB  - Histogranin (HN)-like nonpeptides were designed and synthesized using
      benzimidazole (compound 1) and o-phenylenediamine (compounds 2-7) as scaffolds
      for the attachment of phenolic hydroxyl and basic guanidino pharmacophoric
      elements present in HN. The benzimidazole derivative N-5-guanidinopentanamide
      (2R)-yl-2-(p-hydroxybenzyl)-5-carboxybenzimidazole (1) and the o-phenylenediamine
      derivative N-5-guanidinopentanamide-(2S)-yl-2-N-(p-hydroxyphenylacetyl)
      phenylenediamine (2) were more potent analgesics than HN in both the mouse
      writhing (5.5 and 3.5 as potent as HN, respectively) and tail-flick (11.8 and 8.0
      as potent as HN, respectively) pain assays. Improvements in the potencies and
      times of action of compound 2 in the mouse writhing test were obtained by
      attaching carboxyl (6)or p-Cl-benzoyl (7) groups at position 4 of the (2R) o
      phenylenediamine derivative (5). In rats, compounds 2 (80 nmol i.t.), 6 (36 nmol
      i.t.), and 7 (18 nmol i.t.) were effective in blocking both persistent
      inflammatory pain in the formalin test and hyperalgesia in the complete Freund
      adjuvant assay. Compounds 2, 6, and 7, but not compound 1 at 10 nmol (i.c.v.)
      also mimicked the HN (60 nmol i.c.v.) blockade of N-methyl-D-aspartate (NMDA)
      induced convulsions in mice. Finally, in primary cultures of rat alveolar
      macrophages, HN and compounds 1, 2, 6, and 7 (10(-8) M) significantly blocked
      lipopolysaccharide-induced cyclooxygenase-2 induction and prostaglandin E(2)
      secretion. These studies indicate that both derivatives of benzimidazole and o
      phenylenediamine mimic the in vivo antinociceptive and in vitro anti-inflammatory
      effects of HN, but the HN protection of mice against NMDA-induced convulsions is
      mimicked only by the o-phenylenediamine derivatives.

PMID- 14718587
TI  - NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6
      fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate
      dihydrochloride]: a new selective inhibitor of T-type calcium channels.
AB  - Mibefradil is a Ca2+ channel antagonist that inhibits both T-type and high
      voltage-activated Ca2+ channels. We previously showed that block of high-voltage
      activated channels by mibefradil occurs through the production of an active
      metabolite by intracellular hydrolysis. In the present study, we modified the
      structure of mibefradil to develop a nonhydrolyzable analog, (1S, 2S)-2-(2-(N-[(3
      benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1
      isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride (NNC 55-0396), that
      exerts a selective inhibitory effect on T-type channels. The acute IC(50) of NNC
      55-0396 to block recombinant alpha(1)G T-type channels in human embryonic kidney
      293 cells was approximately 7 microM, whereas 100 microM NNC 55-0396 had no
      detectable effect on high-voltage-activated channels in INS-1 cells. NNC 55-0396
      did not affect the voltage-dependent activation of T-type Ca2+ currents but
      changed the slope of the steady-state inactivation curve. Block of T-type Ca2+
      current was partially relieved by membrane hyperpolarization and enhanced at a
      high-stimulus frequency. Washing NNC 55-0396 out of the recording chamber did not
      reverse the T-type Ca2+ current activity, suggesting that the compound dissolves
      in or passes through the plasma membrane to exert its effect; however,
      intracellular perfusion of the compound did not block T-type Ca2+ currents,
      arguing against a cytoplasmic route of action. After incubating cells from an
      insulin-secreting cell line (INS-1) with NNC 55-0396 for 20 min, mass
      spectrometry did not detect the mibefradil metabolite that causes L-type Ca2+
      channel inhibition. We conclude that NNC 55-0396, by virtue of its modified
      structure, does not produce the metabolite that causes inhibition of L-type Ca2+
      channels, thus rendering it more selective to T-type Ca2+ channels.

PMID- 14718588
TI  - The cognition-enhancer nefiracetam inhibits both necrosis and apoptosis in
      retinal ischemic models in vitro and in vivo.
AB  - The retinal ischemic-reperfusion stress (130 mm Hg, 45 min) caused neuronal
      damage throughout all cell layers and reduced the thickness of retinal layer by
      30% at 7 days after the stress of mouse retina. The intravitreous injection of
      100 pmol of nefiracetam, a cognition-enhancer, completely prevented the damage
      when it was given 30 min before and 3 h after the stress. Partial prevention was
      observed when it was given 24 h after the stress, or low dose (10 pmol)
      nefiracetam was given 30 min before the stress. However, aniracetam had no
      effect. In the retinal cell line N18-RE-105, the ischemic-reperfusion stress by 2
      h culture under the serum-free condition with low oxygen (less of 0.4% O(2)) and
      low glucose (1 mM) caused necrosis or apoptosis in the low-density (0.5 x 10(4)
      cell/cm(2))or high-density (5 x 10(4) cell/cm(2)) culture, respectively. The
      necrosis showed membrane disruption, loss of electron density, and mitochondrial
      swelling, whereas apoptosis showed nuclear fragmentation and condensation in
      transmission electron microscopical analyses and in experiments using specific
      cell death markers. Nefiracetam inhibited both necrosis and apoptosis, whereas
      brain-derived neurotrophic factor (BDNF) inhibited only apoptosis. The cell
      protective actions of nefiracetam were abolished by nifedipine and omega
      conotoxin GVIA, L-type and N-type calcium channel blocker, but not by PD98059 or
      wortmannin, extracellular signal-regulated kinase 1/2 or phosphoinositide 3
      kinase inhibitor, respectively, whereas those of BDNF were abolished by PD98059
      and wortmannin, but not by nifedipine and omega-conotoxin GVIA. All these
      findings suggest that nefiracetam inhibit necrosis and apoptosis occurred in the
      ischemic/hypoxic neuronal injury through an increase in Ca(2+) influx.

PMID- 14718589
TI  - Imatinib-mesylate blocks recombinant T-type calcium channels expressed in human
      embryonic kidney-293 cells by a protein tyrosine kinase-independent mechanism.
AB  - The 2-phenylaminopyrimidine derivative imatinib-mesylate, a powerful protein
      tyrosine kinase (PTK) inhibitor that targets abl, c-kit, and the platelet-derived
      growth factor receptors, is rapidly gaining a relevant role in the treatment of
      several types of neoplasms. Because first generation PTK inhibitors affect the
      activity of a large number of voltage-dependent ion channels, the present study
      explored the possibility that imatinib-mesylate could interfere with the activity
      of T-type channels, a class of voltage-dependent Ca2+ channels that take part in
      the chain of events elicited by PTK activation. The effect of the drug on T-type
      channel activity was examined using the whole-cell patch-clamp technique with
      Ba2+ (10 mM) as the permeant ion in human embryonic kidney-293 cells, stably
      expressing the rat Ca(V)3.3 channels. Imatinib-mesylate concentrations, ranging
      from 30 to 300 microM, reversibly decreased Ca(V)3.3 current amplitude with an
      IC(50) value of 56.9 microM. By contrast, when imatinib-mesylate (500 microM) was
      intracellularly dialyzed with the pipette solution, no reduction in Ba2+ current
      density was observed. The 2-phenylaminopyrimidine derivative modified neither the
      voltage dependence of activation nor the steady-state inactivation of Ca(V)3.3
      channels. The decrease in extracellular Ba2+ concentration from 10 to 2 mM and
      the substitution of Ca2+ for Ba2+ increased the extent of 30 microM imatinib
      mesylate-induced percentage of channel blockade from 25.9 +/- 2.4 to 36.3 +/-
      0.9% in 2 mM Ba2+ and 44.2 +/- 2.3% in 2 mM Ca2+. In conclusion, imatinib
      mesylate blocked the cloned Ca(V)3.3 channels by a PTK-independent mechanism.
      Specifically, the drug did not affect the activation or the inactivation of the
      channel but interfered with the ion permeation process.

PMID- 14718590
TI  - Role of alpha-adrenergic receptors in the effect of the beta-adrenergic receptor
      ligands, CGP 12177, bupranolol, and SR 59230A, on the contraction of rat
      intrapulmonary artery.
AB  - This study investigates the effect of the aryloxypropanolamines 4-[3-[(1,1
      dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one (CGP
      12177), bupranolol, and 3-(2-ethylphenoxy)-1[(1S)-1,2,3,4-tetrahydronaphth-1
      ylamino]-(2S)-2-propanol oxalate (SR 59230A) [commonly used as beta(3)- and/or
      atypical beta-adrenergic receptors (beta-AR) ligands] on the contractile function
      of rat intralobar pulmonary artery. Affinities of beta-AR ligands for alpha(1)
      adrenergic receptors (alpha(1)-AR) were also evaluated using [(3)H]prazosin
      binding competition experiments performed in rat cortical membranes. In
      intralobar pulmonary artery, CGP 12177 did not modify the basal tone, but
      antagonized the contraction induced by the alpha(1)-AR agonist phenylephrine
      (PHE). In arteries precontracted with PHE, CGP 12177 elicited relaxation, whereas
      in those precontracted with prostaglandin F(2alpha) (PGF(2alpha)), it further
      enhanced contraction. CGP 12177 induced an increase in intracellular calcium
      concentration in pressurized arteries loaded with Fura PE-3 and precontracted
      with PGF(2alpha). In PGF(2alpha) precontracted arteries, phentolamine (an alpha
      AR antagonist) and phenoxybenzamine (an irreversible alpha-AR antagonist)
      antagonized the contractile responses to PHE and CGP 12177. Both responses were
      also decreased by bupranolol and SR 59230A. Specific [(3)H]prazosin binding was
      displaced by CGP 12177, bupranolol, and SR 59230A with pK(i) values of 5.2, 5.7,
      and 6.6, respectively. In contrast, (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2
      hydroxyethyl]amino]propyl]phenoxy]acetic acid sodium (BRL 37344) and disodium 5
      [(2R)-2-([(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl]-1,3-benzodioxole
      2,2-dicarboxylate (CL 316243) (nonaryloxypropanolamines beta(3)-AR agonists)
      displayed very low affinity for [(3)H]prazosin binding sites (pK(i) values below
      4). These data suggest that CGP 12177 exhibits partial agonist properties for
      alpha(1)-AR in rat pulmonary artery. They also show that bupranolol and SR 59230A
      exert an alpha(1)-AR antagonist effect. As a consequence, these
      aryloxypropanolamine compounds should be used with caution when investigating the
      role of beta(3)- and atypical beta-AR in the regulation of vascular tone.

PMID- 14718591
TI  - Anandamide is able to inhibit trigeminal neurons using an in vivo model of
      trigeminovascular-mediated nociception.
AB  - Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand
      of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found
      localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus
      caudalis. Known behavioral effects of anandamide are antinociception, catalepsy,
      hypothermia, and depression of motor activity, similar to Delta(9)
      tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a
      possible therapeutic target for migraine. In this study, we looked at the
      possible role of the CB(1) receptor in the trigeminovascular system, using
      intravital microscopy to study the effects of anandamide against various
      vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation
      brought about by electrical stimulation by 50%, calcitonin gene-related peptide
      (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also
      able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide
      inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also
      reduced the blood pressure changes caused by CGRP injection, this effect was not
      reversed by AM251. It would seem that anandamide acts both presynaptically, to
      prevent CGRP release from trigeminal sensory fibers, and postsynaptically to
      inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1)
      receptors seem to be involved in the NO/CGRP relationship that exists in causing
      headache and dural blood vessel dilation. It also seems that some of the blood
      pressure changes caused by anandamide are mediated by a noncannabinoid receptor,
      as AM251 was unable to reverse these effects. It can be suggested that anandamide
      is tonically released to play some form of modulatory role in the
      trigeminovascular system.

PMID- 14718592
TI  - Emerging pharmacologic approaches for the treatment of lower urinary tract
      disorders.
AB  - Lower urinary tract disorders include disorders affecting continence (stress
      urinary incontinence, urge urinary incontinence, and benign prostatic
      hyperplasia) and male erectile dysfunction. Although none of these conditions are
      fatal, they affect overall quality of life. Throughout modern medicine the
      treatment of these conditions was limited to psychological counseling or surgical
      intervention. In recent years, research defining the physiological mechanisms of
      continence and male sexual function has aided in the pharmacologic design of
      approaches to these conditions. These agents can act both centrally or on the
      peripheral genitourinary smooth muscle to alleviate disease symptoms.
      Incontinence is primarily treated with agents that act directly on the bladder
      smooth muscle such as muscarinic antagonists. However, afferent blockade to
      attenuate the spinalbulbospinal reflex pathway including mixed
      norepinephrine/serotonin reuptake inhibitors may provide a key breakthrough.
      Erectile dysfunction treatment has been revolutionized via the discovery of the
      nitric oxide pathway and phosphodiesterase 5 inhibitors. New peripheral targets
      as well as centrally acting agents represent potential emerging therapies. In
      this review, the pharmacologic basis of treatment of these disorders is discussed
      with special emphasis on emerging new therapeutics.

PMID- 14718593
TI  - Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1
      knockout and wild-type mice.
AB  - Mice devoid of CB1 cannabinoid receptors (CB1-/- mice) provide a unique
      opportunity to further investigate the role of CB1 receptors in exocannabinoid
      and endocannabinoid effects. CB1-/- mice (N = 18) and their wild-type littermates
      (CB1+/+ mice; N = 12) were placed in standard mouse operant chambers and trained
      to lever press under a fixed ratio 10 schedule of reinforcement. When stable
      lever press responding under the fixed ratio 10 schedule had been established,
      cannabinoids and noncannabinoids were administered to both groups. CB1+/+ mice
      acquired the lever press response more readily than CB1-/- mice. Delta(9)
      Tetrahydrocannabinol (Delta(9)-THC) decreased lever press responding in CB1+/+
      mice only, whereas methanandamide, a metabolically stable endocannabinoid analog,
      produced similar response rate decreases in both genotypic groups. Similar to
      Delta(9)-THC, another endocannabinoid analog, (R)-(20-cyano-16,16-dimethyl docosa
      cis-5,8,11,14-tetraeno)-1'-hydroxy-2'-propylamine (O-1812), decreased responding
      in CB1+/+ mice, but not in CB1-/- mice. The CB1 receptor antagonist N-(piperidin
      1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride (SR141716A) blocked the effects of Delta(9)-THC, but not those of
      methanandamide. Because methanandamide binds poorly to CB2 receptors, these
      results suggest possible non-CB1, non-CB2 mechanisms of action for methanandamide
      induced behavioral disruption of lever press responding. Ethanol and morphine
      elicited greater response decreases in CB1-/- mice than in CB1+/+ mice,
      suggesting a possible role of CB1 receptors in the rate disruptive effects of
      these drugs. In contrast, diazepam did not produce between group differences,
      suggesting that CB1 receptors are not involved in diazepam-induced disruption of
      lever press responding.

PMID- 14718594
TI  - Novel dual action AT1 and ETA receptor antagonists reduce blood pressure in
      experimental hypertension.
AB  - Angiotensin II and endothelin-1 activate their respective AT(1) and ET(A)
      receptors on vascular smooth muscle cells, producing vasoconstriction, and both
      peptides are implicated in the pathogenesis of essential hypertension.
      Angiotensin II potentiates the production of endothelin, and conversely
      endothelin augments the synthesis of angiotensin II. Both AT(1) and ET(A)
      receptor antagonists lower blood pressure in hypertensive patients; thus, a
      combination AT(1)/ET(A) receptor antagonist may have greater efficacy and broader
      utility compared with each drug alone. By rational drug design a biphenyl ET(A)
      receptor blocker was modified to acquire AT(1) receptor antagonism. These
      compounds (C and D) decreased Sar-Ile-Angiotensin II binding to AT(1) receptors
      and endothelin-1 binding to ET(A) receptors, and compound C inhibited angiotensin
      II- and endothelin-1-mediated Ca(2+) transients. In rats compounds C and D
      reduced blood pressure elevations caused by intravenous infusion of angiotensin
      II or big endothelin-1. Compound C decreased blood pressure in Na(+)-depleted
      spontaneously hypertensive rats and in rats with mineralocorticoid hypertension.
      Compound D was more efficacious than AT(1) receptor antagonists at reducing blood
      pressure in spontaneously hypertensive rats, and its superiority was likely due
      to its partial blockade of ET(A) receptors. Therefore compounds C and D are novel
      agents for treating a broad spectrum of patients with essential hypertension and
      other cardiovascular diseases.

PMID- 14718595
TI  - Discriminative stimulus effects of gamma-hydroxybutyrate in pigeons: role of
      diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors.
AB  - gamma-Hydroxybutyrate (GHB) is an emerging drug of abuse with multiple mechanisms
      of action. This study is part of an effort to examine the role of GHB, GABA(A),
      and GABA(B) receptors in the discriminative stimulus (DS) effects of GHB. In
      pigeons trained to discriminate 100 mg/kg GHB from saline, GHB and its precursors
      gamma-butyrolactone and 1,4-butanediol produced 80 to 100% GHB-appropriate
      responding, whereas other compounds such as morphine, naltrexone, cocaine, and
      haloperidol produced no more than 34%. Compounds interacting with GABA receptors
      produced different maximal levels of GHB-appropriate responding. For example, the
      GABA(A) agonist muscimol produced 3%; the GABA(A)-positive modulators diazepam,
      pentobarbital, and ethanol, and the GABA(B) agonist baclofen produced levels
      ranging from 54 to 73%; and the benzodiazepine antagonist flumazenil and inverse
      agonist Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]
      [1,4]-benzodiazepine-3-carboxylate) both produced 96%. The putative GHB receptor
      antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene
      ethanoic acid (NCS-382) produced 70% GHB-appropriate responding. The GABA(B)
      antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP 35348) completely
      blocked the GHB-like DS effects of NCS-382 and baclofen at a dose of 56 mg/kg.
      CGP 35348 also blocked the DS effects of GHB, but incompletely and only at a dose
      of 560 mg/kg. Together, these results are consistent with a role for diazepam
      sensitive and -insensitive GABA(A) and GABA(B) receptors in the DS effects of
      GHB. Together with previous findings, the present results suggest that diazepam
      insensitive GABA(A) receptors are more prominently involved in the DS effects of
      GHB in pigeons than in rats, whereas GABA(B) receptors are less prominently
      involved. Exploring the role of GHB receptors with NCS-382 is hampered by its
      GABA(B) receptor-mediated, GHB-like agonist activity.

PMID- 14718596
TI  - Suppression of 15-hydroxyprostaglandin dehydrogenase messenger RNA concentration,
      protein expression, and enzymatic activity during human ureteral obstruction.
AB  - Prostanoids produce significant effects in the ureter, particularly in response
      to obstruction. Ureteral obstruction is associated with increased prostanoid
      synthesis via cyclooxygenase induction; however, prostaglandin degradation
      mediated by 15-hydroxyprostaglandin dehydrogenase (PGDH) has not been evaluated
      in the ureter. The purpose of this study was to determine whether PGDH steady
      state mRNA, protein, and enzyme activity are altered in the human ureter during
      obstruction. Human ureteral segments from patients undergoing donor nephrectomy
      (normal segments) or ureteral stricture repair (obstructed segments) were
      obtained with proper informed consent. We evaluated PGDH steady-state mRNA
      relative to ribosomal protein S26 reference gene by reverse transcription
      polymerase chain reaction and Vistra Green fluoroimaging. We determined PGDH
      protein content relative to glyceraldehyde-3-phosphate dehydrogenase by
      immunoblotting and PGDH localization by immunohistochemistry. PGDH enzymatic
      activity was determined by measurement of conversion of 15-hydroxy- to 15-keto
      prostaglandin using thin layer chromatography separation. We found that PGDH mRNA
      and protein were decreased 4- to 6-fold, and enzyme activity was decreased >3
      fold in obstructed human ureter relative to normal controls. PGDH was localized
      to the urothelial cells, with little or no expression in smooth muscle. Our
      results indicate that PGDH mRNA, protein, and enzyme activity are suppressed in
      the human ureter during obstruction. Increased concentrations of prostanoids
      subsequent to ureteral obstruction seem to be due to decreased degradation as
      well as increased synthesis. Modulation of prostanoid degradation may have
      therapeutic relevance in obstructive disorders of the ureter.

PMID- 14718597
TI  - Novel and selective small molecule stimulators of osteoprotegerin expression
      inhibit bone resorption.
AB  - Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor
      superfamily, is a potent inhibitor of osteoclast formation and bone resorption.
      Because OPG functions physiologically as a locally generated (paracrine) factor,
      we used high-throughput screening to identify small molecules that enhance the
      activity of the promoter of the human OPG gene. We found three structurally
      unrelated compounds that selectively increased OPG gene transcription, OPG mRNA
      levels, and OPG protein production and release by osteoblastic cells. Structural
      analysis of one compound, a benzamide derivative, led to the identification of
      four related molecules, which are also OPG inducers. The most potent of these
      compounds, Cmpd 5 inhibited osteoclast formation and parathyroid hormone-induced
      calvarial bone resorption. In vivo, Cmpd 5 completely blocked resorptive activity
      (serum calcium, osteoclast number) in parathyroid hormone-treated rats.
      Furthermore, Cmpd 5 reduced the ability of a rat breast cancer to metastasize to
      bone. Finally, the compound also prevented bone loss in a rat adjuvant arthritis
      model. These results provide proof of the concept that low molecular weight
      compounds can enhance OPG production in ways that can result in effective
      therapies.

PMID- 14718598
TI  - Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon
      ischemic insult in the rat heart.
AB  - To test the hypothesis that estrogen confers cardioprotection by suppressing the
      expression of beta-adrenoceptor (beta-AR), we first correlated the infarct size
      in response to ischemic insult and beta-AR stimulation with the expression of
      beta(1)-AR in sham, ovariectomized (Ovx) and estrogen replaced (Ovx + E(2)) rats.
      When beta-AR is being activated during ischemia, the infarct size was
      significantly greater in Ovx than in the sham and Ovx + E(2) rats. There is a
      negative correlation between the infarct size and the expression level of beta(1)
      AR as revealed by Western blotting and supported by binding analysis. Incubation
      of ventricular myocytes from Ovx rats with estrogen at 10(-9) M for 24 and 48 h,
      but not 12 h, significantly reduced lactate dehydrogenase release when the
      myocytes are subjected to simulated ischemia. The cardioprotective effect of 24 h
      estrogen incubation was accompanied by a reduction in the protein expression
      level of beta(1)-AR, which is estrogen receptor-dependent, whereas the lack of
      protection of 12-h estrogen incubation was not accompanied by any alterations in
      the expression level of beta(1)-AR. Together, the result from present study
      suggested that it is most likely that the cardioprotective effect of long-term
      estrogen replacement is due to suppressing the enhanced expression of cardiac
      beta(1)-AR in the Ovx rats, which in turn reduces cardiac injury when beta-AR is
      activated by sympathetic hyperactivity during ischemia. Therefore, suppression of
      the enhanced expression of cardiac beta(1)-AR in Ovx rats represents a novel
      cardioprotective mechanism of estrogen replacement therapy.

PMID- 14718599
TI  - Transport of pharmacologically active proline derivatives by the human proton
      coupled amino acid transporter hPAT1.
AB  - Several proline derivatives such as L-azetidine-2-carboxylic acid, cis-4-hydroxy
      L-proline, and 3,4-dehydro-DL-proline prevent procollagen from folding into a
      stable triple-helical conformation, thereby reducing excessive deposition of
      collagen in fibrotic processes and the growth of tumors. This study was performed
      to investigate whether the recently discovered human proton-coupled amino acid
      transporter 1 (hPAT1) is capable of transporting such pharmacologically relevant
      proline derivatives and also GABA analogs. Uptake of L-[3H]proline and
      [3H]glycine in Caco-2 cells was Na+-independent but strongly H+-dependent. The L
      proline uptake was saturable and mediated by a single transport system (hPAT1)
      with an affinity constant of 2.0 +/- 0.2 mM. The uptake of L-[3H]proline was
      inhibited by D-proline, trans-4-hydroxy-L-proline, cis-4-hydroxy-L-proline, cis-4
      hydroxy-D-proline, 3,4-dehydro-DL-proline, L-azetidine-2-carboxylic acid, 3-amino
      1-propanesulfonic acid, D- and L-pipecolic acid, l-thiaproline, and many others.
      Apical uptake and transepithelial flux of L-[3H]proline across Caco-2 cell
      monolayers were strongly inhibited by proline derivatives in proportions
      corresponding to their respective affinity constants at hPAT1. The basolateral to
      apical flux of L-[3H]proline was only 8% of that in the opposite direction.
      Apical uptake of unlabeled L-proline, cis-4-hydroxy-L-proline, and L-azetidine-2
      carboxylic acid was stimulated by an inside directed H+ gradient 2- to 3-fold.
      Total apical to basolateral flux of proline derivatives was moderately correlated
      with their inhibitory potency for L-[3H]proline uptake and flux inhibition. We
      conclude that 1) the substrate specificity of hPAT1 is very much broader than so
      far reported and 2) the system accepts therapeutically relevant proline and GABA
      derivatives. hPAT1 is a promising candidate for new ways of oral drug delivery.

PMID- 14718600
TI  - Action of bradykinin in the submucosal plexus of guinea pig small intestine.
AB  - Intracellular recording methods with "sharp" microelectrodes were used to study
      actions of bradykinin (BK) on electrical behavior of morphologically identified
      neurons and the identification and localization of BK receptors in the submucosal
      plexus of guinea pig small intestine. Exposure to BK depolarized the membrane
      potential and elevated excitability in submucosal neurons with AH-type
      electrophysiological behavior and Dogiel II multipolar morphology and in neurons
      with S-type electrophysiological behavior and uniaxonal morphology. BK-evoked
      depolarizing responses were associated with increased neuronal input resistance
      in AH-type neurons and decreased input resistance in S-type neurons. The
      selective B(2) BK receptor antagonists HOE-140 (icatabant acetate) and WIN64338
      [(S)-4[2-bis(cyclohexylamino)methyleneamino]-3-(2-napthalenyl)-1
      oxopropylamino]benzyl tributyl phosphonium chloride hydrochloride], but not the
      selective B(1) receptor antagonists des-arg(10)-HOE-140 and des-arg(9)-leu(8)-BK,
      suppressed the BK-evoked responses. The selective B(2) receptor agonist Kallidin,
      but not the selective B(1) receptor agonist des-arg(9)-BK mimicked the excitatory
      action of BK. Western blot analysis and reverse transcription-polymerase chain
      reaction confirmed the expression of B(2) receptor protein and mRNA. Binding
      studies with a fluorescently labeled BK(2) antagonist found expression of B(2)
      receptors on a majority of the ganglion cells. B(2) receptors occupied 82% of the
      neurons that expressed immunoreactivity for neuropeptide Y, 75% of the neurons
      that expressed vasoactive intestinal peptide, 84% of the neurons that expressed
      substance P, 71% of the neurons that expressed choline acetyltransferase, and all
      neurons that expressed calbindin immunoreactivity. The results suggest that the
      B(2) receptor mediates the excitatory action of BK on submucosal plexus neurons.
      Pathophysiological significance of the excitatory actions on secretomotor neurons
      might be stimulated mucosal secretion and the secretory diarrhea associated with
      intestinal inflammatory states.

PMID- 14718601
TI  - Metabotropic signal transduction for bradykinin in submucosal neurons of guinea
      pig small intestine.
AB  - Intracellular recording methods with "sharp" microelectrodes were used to study
      signal transduction mechanisms underlying the excitatory action of bradykinin
      (BK) in morphologically identified neurons in the small intestinal submucosal
      plexus. Exposure to BK evoked slowly activating membrane depolarization and
      enhanced excitability associated with increased input resistance in AH-type and
      decreased input resistance in S-type neurons. Preincubation with pertussis toxin
      did not affect the BK-evoked responses. Pretreatment with the cyclooxygenase
      inhibitors indomethacin or piroxicam suppressed or abolished the BK-evoked
      responses. Application of prostaglandin (PG) E(2) or PG analogs evoked BK-like
      depolarizing responses in the submucosal plexus with a potency order of PGE(2) >
      PGE(1) > 17-phenyl trinor-PGE(2) > PGI(2) > sulprostone > PGF(2alpha).
      Depolarizing responses to bradykinin or PGE(2) in S-type neurons were suppressed
      in the presence of the phospholipase C inhibitor U73122 [(1-6-[([17beta]-3
      methoxyestra-1,3,5[10]-tren-17-71)amino]hexyl)-1H-pyrrole-2,5-dione)], but not
      the inactive analog U73343 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]trien
      17yl)amino]hexyl)-2,5-pyrrolidinedione)]. The inositol-1,4,5-trisphosphate
      receptor antagonist 2-aminoethoxy-diphenylborane and the calmodulin inhibitor W
      7, but not ryanodine, suppressed both bradykinin- and PGE(2)-evoked responses. KN
      62, an inhibitor of calmodulin kinases, or GF109203X, a specific protein kinase C
      inhibitor, suppressed both BK- and PGE(2)-evoked depolarizing responses.
      Selective protein kinase A inhibitors did not alter BK- or PGE(2)-evoked
      depolarizing responses in S neurons. The results suggest that BK stimulates
      synthesis and release of PGE(2), which acts at EP(1) receptors to evoke
      depolarizing responses in submucosal neurons. The postreceptor transduction
      cascade includes activation of phospholipase C, inositol-1,4,5-trisphosphate
      production, intraneuronal Ca2+ mobilization, activation of protein kinase C
      and/or calmodulin kinases, and phosphorylation of cationic channels.

PMID- 14718602
TI  - NAD(P)H:quinone oxidoreductase-1-dependent and -independent cytotoxicity of
      potent quinone Cdc25 phosphatase inhibitors.
AB  - Cdc25 dual-specificity phosphatases coordinate cell cycle progression and
      cellular signaling. Consequently, Cdc25 inhibitors represent potential anticancer
      agents. We evaluated >10,000 compounds for inhibition of human Cdc25 phosphatases
      and identified many potent and selective inhibitors, which all contained a
      quinone. Bioreductive enzymes frequently detoxify or activate quinones.
      Therefore, we evaluated the effect of NAD(P)H:quinone oxidoreductase-1 (NQO1) and
      reductase-rich microsomes on the activity of three quinone-containing Cdc25
      inhibitors: 2-(2-hydroxyethylsulfanyl)-3-methyl-1,4-naphthoquinone (Cpd 5,
      compound 5; NSC 672121), 2,3-bis-(2-hydroxyethylsulfanyl)-1,4-naphthoquinone (NSC
      95397), and 6-chloro-7-(2-morpholin-4-yl-ethylamino)quinoline-5,8-dione (NSC
      663284). Each inhibitor was reduced by human NQO1 (K(m) of 0.3-0.5 microM) but
      none by microsomes. Compounds were evaluated with six cancer cell lines
      containing different amounts of NQO1: HT-29 (1056 nmol/mg/min), HCT116 (660
      nmol/mg/min), sublines HCT116-R30A (28 nmol/mg/min) and HCT-116R30A/NQ5 (934
      nmol/mg/min), MDA-MB-231/Q2 (null NQO1), and subline MDA-MB-231/Q6 (124
      nmol/mg/min) but containing similar amounts of microsomal cytochrome P450
      reductase and cytochrome b(5) reductase. Growth inhibition and G2/M arrest by Cpd
      5 was proportional to NQO1 levels, requiring 4- to 5-fold more Cpd 5 to inhibit
      HCT-116 or HCT-116R30A/NQ5 compared with HCT-116R30A. In contrast, in all tested
      cell lines irrespective of NQO1 level, growth inhibition and G2/M arrest by NSC
      95375 and NSC 663284 were similar (average IC(50) of 1.3 +/- 0.3 and 2.6 +/- 0.4
      microM, respectively). NSC 95375 and NSC 663284 also caused similar Cdk1
      hyperphosphorylation, indicating similar Cdc25 inhibition. However, lower Cpd 5
      concentrations were needed to produce Cdk1 hyperphosphorylation in sublines with
      minimal NQO1. Thus, NQO1 detoxified Cpd 5, probably by reducing it to a less
      active hydroquinone, whereas NSC 95397- and NSC 663284-generated cytotoxicity was
      unaffected by NQO1.

PMID- 14718603
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin, an exogenous modulator of the 3'alpha
      immunoglobulin heavy chain enhancer in the CH12.LX mouse cell line.
AB  - Transcriptional regulation of the Ig heavy chain gene involves several regulatory
      elements, including the 3'alpha enhancer, which is composed of four distinct
      regulatory domains. DNA binding sites for several transcription factors,
      including B cell-specific activator protein, nuclear factor for immunoglobulin
      kappa chain in B cells, and octamer have been identified within the 3'alpha
      enhancer domains and are believed to be important in regulating 3'alpha enhancer
      activity. We have identified an additional DNA binding motif, the dioxin
      responsive element (DRE), which can contribute to 3'alpha enhancer regulation.
      2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a known disrupter of B cell
      differentiation (i.e., decreased plasma cell formation, inhibition of micro heavy
      chain expression, and suppression of IgM secretion), induces binding of the aryl
      hydrocarbon receptor (AhR) nuclear complex to DREs. TCDD also induces AhR binding
      to the hypersensitive (hs)4 domain of the 3'alpha enhancer. Interestingly, TCDD
      enhances LPS-induced activation of the hs4 domain but profoundly inhibits LPS
      induced activation of the complete 3'alpha enhancer. Furthermore, site-directed
      mutational analysis demonstrated that a DRE and kappaB element in the hs4 domain
      is modulated by TCDD in lipopolysaccharide-activated B cells. We propose that the
      AhR is a novel transcriptional regulator of the 3'alpha enhancer, which can
      mediate, at least in part, the effects of TCDD on the 3'alpha enhancer and its
      domains, putatively contributing to a marked suppression of IgM production.

PMID- 14718604
TI  - In vitro and in vivo anti-inflammatory activity of the new glucocorticoid
      ciclesonide.
AB  - The glucocorticoid ciclesonide is the 2'R-epimer of 2'-cyclohexyl-11beta-hydroxy
      21-isobutyryloxy-16bH-dioxolo[5',4':16,17]pregna-1,4-diene-3,20-dione. The active
      metabolite desisobutyryl-ciclesonide (des-CIC) is derived from ciclesonide by
      esterase cleavage of isobutyrate at the C21 position. The relative binding
      affinities at the rat glucocorticoid receptor were dexamethasone, 100;
      ciclesonide, 12; des-CIC, 1212; and budesonide, 905. Des-CIC potently inhibited
      the activation of murine and human lymphocytes in a series of different in vitro
      systems. With the exception of concanavalin A-stimulated rat spleen cells, des
      CIC was more potent than the parent compound. Des-CIC compared well with
      budesonide in all in vitro systems. Furthermore, the respective 2'S-epimers were
      always significantly less potent than the 2'R-epimers. In vivo, ciclesonide
      (intratracheal administration), des-CIC, and budesonide inhibited antigen-induced
      accumulation of eosinophils, protein, and tumor necrosis factor-alpha into the
      bronchoalveolar lavage fluid of ovalbumin-sensitized and -challenged Brown Norway
      rats with an ED(50) value ranging from 0.4 to 1.3 mg/kg, indicating similar
      potency, which suggests in vivo activation of the parent compound. Ciclesonide
      and budesonide inhibited the bradykinin-induced protein leakage into the rat
      trachea. In the rat cotton pellet model, ciclesonide inhibited granuloma
      formation (ED(50):= of 2 microg/pellet), whereas budesonide and des-CIC were 15-
      and 20-fold less active; thymus involution was induced with an ED(50) of 303,
      279, and 154 microg/pellet, respectively. When applied orally to rats for 28
      days, ciclesonide showed low potency in reducing weight of thymus and adrenals,
      suggesting low oral bioavailability. The in vivo data on ciclesonide highlight
      its effective local action and a reduced potential for side effects.

PMID- 14718605
TI  - Identification and characterization of 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N
      hydroxy-2,2-dimethyl-(3S)thiomorpholinecarboxamide (TMI-1), a novel dual tumor
      necrosis factor-alpha-converting enzyme/matrix metalloprotease inhibitor for the
      treatment of rheumatoid arthritis.
AB  - Tumor necrosis factor (TNF)-alpha is a well validated therapeutic target for the
      treatment of rheumatoid arthritis. TNF-alpha is initially synthesized as a 26-kDa
      membrane-bound form (pro-TNF) that is cleaved by a Zn-metalloprotease named TNF
      alpha-converting enzyme (TACE) to generate the 17-kDa, soluble, mature TNF-alpha.
      TACE inhibitors that prevent the secretion of soluble TNF-alpha may be effective
      in treating rheumatoid arthritis (RA) patients. Using a structure-based design
      approach, we have identified a novel dual TACE/matrix metalloprotease (MMP)
      inhibitor 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl
      (3S)thiomorpholinecarboxamide (TMI-1). This molecule inhibits TACE and several
      MMPs with nanomolar IC(50) values in vitro. In cell-based assays such as monocyte
      cell lines, human primary monocytes, and human whole blood, it inhibits
      lipopolysaccharide (LPS)-induced TNF-alpha secretion at submicromolar
      concentrations, whereas there is no effect on the TNF-alpha mRNA level as judged
      by RNase protection assay. The inhibition of LPS-induced TNF-alpha secretion is
      selective because TMI-1 has no effect on the secretion of other proinflammatory
      cytokines such as interleukin (IL)-1beta, IL-6, and IL-8. Importantly, TMI-1
      potently inhibits TNF-alpha secretion by human synovium tissue explants of RA
      patients. In vivo, TMI-1 is highly effective in reducing clinical severity scores
      in mouse prophylactic collagen-induced arthritis (CIA) at 5, 10, and 20 mg/kg
      p.o. b.i.d. and therapeutic CIA model at 100 mg/kg p.o. b.i.d. In summary, TMI-1,
      a dual TACE/MMP inhibitor, represents a unique class of orally bioavailable small
      molecule TNF inhibitors that may be effective and beneficial for treating RA.

PMID- 14718606
TI  - Ethanol drinking and deprivation alter dopaminergic and serotonergic function in
      the nucleus accumbens of alcohol-preferring rats.
AB  - The alcohol deprivation effect is a temporary increase in the intake of, or
      preference for, ethanol after a period of deprivation that may result from
      persistent changes in key limbic regions thought to regulate alcohol drinking,
      such as the nucleus accumbens. The present study tested the hypothesis that
      chronic alcohol drinking under continuous 24-h free-choice conditions alters
      dopamine and serotonin neurotransmission in the nucleus accumbens and that these
      alterations persist in the absence of alcohol. Using the no-net-flux
      microdialysis method, the steady-state extracellular concentration (point of no
      net-flux) for dopamine was approximately 25% higher in the adult female alcohol
      preferring P rats given prior access to 10% ethanol, even after 2 weeks of
      ethanol abstinence, compared with the P rats gives access only to water. However,
      the extracellular concentration of serotonin was approximately 35% lower in
      animals given 8 weeks of continuous access to ethanol compared with water
      controls and animals deprived of ethanol for 2 weeks. The effect of local
      perfusion with 100 microM sulpiride (D(2) receptor antagonist) and 35 microM 1-(m
      chlorophenyl)-biguanide (5-hydroxytryptamine(3) receptor agonist) on dopamine
      overflow were reduced approximately 33% in both groups of ethanol-exposed P rats
      compared with water controls. Free-choice alcohol drinking by P rats alters
      dopamine and serotonin neurotransmission in the nucleus accumbens, and many of
      these effects persist for at least 2 weeks in the absence of ethanol, suggesting
      that these underlying persistent changes may be in part responsible for increased
      ethanol drinking observed in the alcohol-deprivation effect.

PMID- 14718607
TI  - Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the
      intestinal first-pass extraction of saquinavir.
AB  - Using CYP3A4-expressing Caco-2 cell monolayers, we assessed the roles of CYP3A4
      mediated metabolism, P-glycoprotein (P-gp)-mediated efflux, and serum protein
      binding in determining the extent of the intestinal first-pass extraction (E(i))
      of saquinavir. Saquinavir (5-40 microM) was added to the apical compartment of
      culture inserts. After 3 h, apical and basolateral media and cell scrapings were
      analyzed for saquinavir and a major CYP3A4-mediated metabolite (M7). The
      intracellular concentration of saquinavir was estimated from the degree of
      inhibition of CYP3A4 catalytic activity (midazolam 1'-hydroxylation). Compared
      with vehicle, the P-gp inhibitor LY335979 (zosuquidar trihydrochloride) (0.5
      microM, apical) increased saquinavir cell content and M7 formation rate, but
      decreased the E(i) by approximately 50% due to a >90% increase in the amount of
      saquinavir recovered in the basolateral compartment. Compared with LY335779,
      physiological concentrations of basolateral serum proteins [human serum albumin
      and alpha1-acid glycoprotein (AAG)] increased saquinavir permeability by a
      similar degree but decreased the E(i) by approximately 50% due to a marked
      reduction in M7 formation. Increasing AAG concentration (1.0-2.5 g/l) had no
      additional effect on permeability or E(i). An estimate of the range of the E(i)
      of saquinavir (7-60%) was less than has been predicted based on in vitro data
      (>99%) but was consistent with a clinical study involving grapefruit juice. The
      incidental finding of greater M7 formation after basolateral compared with apical
      dosing could not be explained by differences in saquinavir cell content. We
      conclude that variable intestinal first-pass extraction of saquinavir in human
      immunodeficiency virus-infected patients could reflect variation in P-gp-mediated
      efflux and/or CYP3A4-catalyzed metabolism, but not in blood AAG levels.

PMID- 14718608
TI  - Reduced expression of organic cation transporters rOCT1 and rOCT2 in experimental
      diabetes.
AB  - Recent reports have documented a functional deficit of organic cation transport
      in diabetic rats by an unknown mechanism. This study was designed to test the
      hypothesis that experimental diabetes decreases expression of organic cation
      transporters at the basolateral membrane. Streptozotocin-induced diabetic rats
      were maintained for varying durations after induction of diabetes. A second group
      of age-matched control rats was maintained in a parallel manner. Kinetic analysis
      of tetraethylammonium accumulation in freshly isolated proximal tubular cells
      indicated a significantly lower V(max) value for the diabetics versus controls
      with no statistical difference in K(m) values between the two groups. Cortex
      sections were processed by standard procedures for Northern and immunoblot
      analysis. Protein expression of the organic cation transporters rOCT1 and rOCT2
      progressively decreased with increasing duration of diabetes. After 21 days of
      diabetes, rOCT1 and rOCT2 were maximally reduced by 50 and 70%, respectively.
      Quantification of mRNA expression revealed that the roct1 transcript remained
      unchanged, whereas the roct2 transcript was decreased by 50% after 14 days of
      diabetes. Treatment with insulin prevented the reductions in transporter levels.
      These results support the hypothesis by demonstrating that experimental diabetes
      decreased expression of both rOCT1 and rOCT2 protein and also of roct2 mRNA
      accumulation. On the other hand, roct1 mRNA levels were unaffected by the
      diabetic state. This suggests that differences in rOCT2 protein may result from
      transcriptional and/or translational changes, whereas rOCT1 deficits may be due
      to posttranscriptional alterations.

PMID- 14718609
TI  - Mechanism-based pharmacokinetic-pharmacodynamic modeling of 5-HT1A receptor
      agonists: estimation of in vivo affinity and intrinsic efficacy on body
      temperature in rats.
AB  - The pharmacokinetic-pharmacodynamic (PK-PD) correlations of seven prototypical 5
      HT(1A) agonists were analyzed on the basis of a recently proposed semi
      mechanistic PK-PD model for the effect on body temperature. The resulting
      concentration-effect relationships were subsequently analyzed on the basis of the
      operational model of agonism to estimate the operational affinity (pK(A)) and
      efficacy (log tau) at the 5-HT(1A) receptor in vivo. The values obtained in this
      manner were compared with estimates of the affinity (pK(i)) and intrinsic
      efficacy (log[agonist ratio]) in a receptor-binding assay. Between 5-HT(1A)
      agonists wide differences in in vivo affinity and efficacy were observed, with
      values of the pK(A) ranging from 5.67 for flesinoxan to 8.63 for WAY-100,635 [N
      (2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl
      cyclohexanecarboxamide] and of the log tau ranging from -1.27 for WAY-100,135 [N
      (1,1-dimethylethyl)-4-(2-methoxyphenyl)-alpha-phenyl-1-piperazine-propanamide] to
      0.62 for R-(+)-8-hydroxy-2-[di-n-propylamino)tetralin. Poor correlations were
      observed between the in vivo receptor affinity (pK(A)) and the affinity estimates
      in the in vitro receptor binding assay (pK(i); r(2) = 0.55, P > 0.05), which
      could in part be explained by differences in blood-brain distribution. In
      contrast, a highly significant correlation was observed between the efficacy
      parameters in vivo (log tau) and in vitro (log [agonist ratio]; r(2) = 0.76, P <
      0.05). Thus by combining the previously proposed semi-mechanistic PK-PD model for
      the effect on body temperature with the operational model of agonism, a full
      mechanistic PK-PD model for 5-HT(1A) receptor agonists has been obtained, which
      is highly predictive of the in vivo intrinsic efficacy.

PMID- 14718610
TI  - Loss of sodium modulation of plasma kinins in human hypertension.
AB  - We studied the effect of salt intake and hypertension on the systemic kallikrein
      kinin system (KKS), as measured by bradykinin (BK) 1-5, a stable circulating
      bradykinin metabolite, and the tissue KKS, as measured by urinary kallikrein
      excretion. Venous BK 1-5, urinary kallikrein, and components of the renin
      angiotensin-aldosterone system were measured in 35 normotensive and 19
      hypertensive subjects who were maintained on a high (200 mmol/day) or low (10
      mmol/day) salt diet. Salt restriction decreased mean arterial pressure (MAP) (P <
      0.001 overall) and the plasma angiotensin-converting enzyme (P = 0.017) and
      increased plasma renin activity (P < 0.001) and serum aldosterone (P < 0.001).
      There was an interactive effect of salt intake and hypertension on plasma BK 1-5
      (P = 0.043), with BK 1-5 significantly lower during low compared with high salt
      intake in normotensive (24.7 +/- 2.6 versus 34.9 +/- 5.6 fmol/ml, P = 0.002) but
      not hypertensive subjects (30.6 +/- 4.6 versus 27.5 +/- 2.8 fmol/ml, P = 0.335).
      In normotensives, the change in plasma BK 1-5 from high to low salt intake
      correlated with the change in MAP (r = 0.533, P = 0.004). Urinary kallikrein was
      higher during low compared with high salt intake (P < 0.001) in both groups.
      There was no effect of salt intake on urinary BK 1-5. In summary, the systemic
      and renal KKSs act in tandem to modulate the response to salt intake. The
      systemic system is activated during high salt intake and counterbalances
      increased vascular response to pressors. With sodium restriction, the renal
      system is activated and counterbalances the increased sodium-retaining state
      induced by activation of the renin-angiotensin-aldosterone system. With
      hypertension, these modulating effects are diminished or lost, supporting a role
      for both systems in the development/maintenance of hypertension.

PMID- 14718611
TI  - Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is
      a highly efficacious kappa-opioid receptor agonist: structural and functional
      considerations.
AB  - The diterpene salvinorin A from Salvia divinorum has recently been reported to be
      a high-affinity and selective kappa-opioid receptor agonist (Roth et al., 2002).
      Salvinorin A and selected derivatives were found to be potent and efficacious
      agonists in several measures of agonist activity using cloned human kappa-opioid
      receptors expressed in human embryonic kidney-293 cells. Thus, salvinorin A,
      salvinorinyl-2-propionate, and salvinorinyl-2-heptanoate were found to be either
      full (salvinorin A) or partial (2-propionate, 2-heptanoate) agonists for
      inhibition of forskolin-stimulated cAMP production. Additional studies of agonist
      potency and efficacy of salvinorin A, performed by cotransfecting either the
      chimeric G proteins Gaq-i5 or the universal G protein Ga16 and quantification of
      agonist-evoked intracellular calcium mobilization, affirmed that salvinorin A was
      a potent and effective kappa-opioid agonist. Results from structure-function
      studies suggested that the nature of the substituent at the 2-position of
      salvinorin A was critical for kappa-opioid receptor binding and activation.
      Because issues of receptor reserve complicate estimates of agonist efficacy and
      potency, we also examined the agonist actions of salvinorin A by measuring
      potassium conductance through G protein-gated K(+) channels coexpressed in
      Xenopus oocytes, a system in which receptor reserve is minimal. Salvinorin A was
      found to be a full agonist, being significantly more efficacious than (trans)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane
      sulfonate hydrate (U50488) or (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)
      cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U69593) (two standard
      kappa-opioid agonists) and similar in efficacy to dynorphin A (the naturally
      occurring peptide ligand for kappa-opioid receptors). Salvinorin A thus
      represents the first known naturally occurring non-nitrogenous full agonist at
      kappa-opioid receptors.

PMID- 14718612
TI  - Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in
      mesencephalic neuron-glia cultures by inhibiting microglial activation.
AB  - Inflammation plays an important role in the pathogenesis of several
      neurodegenerative diseases, including Parkinson's disease. Recent reports have
      indicated that andrographolide (ANDRO) has an anti-inflammatory effect by
      modulating macrophage and neutrophil activity. Whereas microglia, the counterpart
      of macrophages in the brain, are pivotal in the inflammatory process in the
      central nervous system, the effect of ANDRO on inflammation-mediated
      neurodegeneration has not been examined. In this study, we show that both
      pretreatment and post-treatment with ANDRO exhibited a significant protective
      effect against lipopolysaccharide (LPS)-induced neurotoxicity in mixed neuron
      glia cultures, as determined by [(3)H]dopamine uptake and immunocytochemical
      analysis. In contrast, ANDRO showed no protective effect on 1-methyl-4-phenyl
      pyridine (0.5 microM)-induced neurotoxicity in neuron-enriched cultures. ANDRO
      significantly attenuated LPS-induced microglial activation and production of
      reactive oxygen species, tumor necrosis factor-alpha, nitric oxide, and
      prostaglandin E(2). Furthermore, ANDRO dose-dependently attenuated LPS-induced
      inducible nitric-oxide synthase and cyclooxygenase-2 protein expression in BV-2
      microglia, as determined by Western blot. These findings demonstrate that ANDRO
      reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic
      neuron-glia cultures by inhibiting microglial activation. In addition, these
      results indicate that ANDRO may have clinical utility for the treatment of
      inflammation-related neurodegenerative disorders such as Parkinson's disease.

PMID- 14718613
TI  - Endogenous betaretroviruses of sheep: teaching new lessons in retroviral
      interference and adaptation.
AB  - The endogenous betaretroviruses of small ruminants offer an excellent model to
      investigate the biological relevance of endogenous retroviruses (ERVs).
      Approximately twenty copies of endogenous betaretroviruses (enJSRVs) are present
      in the genome of sheep and goats. enJSRVs are highly related to Jaagsiekte sheep
      retrovirus (JSRV) and the Enzootic nasal tumour virus (ENTV), the causative
      agents of naturally occurring carcinomas of the respiratory tract of sheep.
      enJSRVs interact/interfere at different levels both with the host and with their
      exogenous and pathogenic counterparts. enJSRVs blocks the exogenous JSRV
      replication by a novel two-step interference mechanism acting both early and late
      during the virus replication cycle. enJSRVs are highly active, they are
      abundantly and specifically expressed in the epithelium of most of the ovine
      female reproductive tract. The specific spatial and temporal expression of
      enJSRVs supports a role in trophoblast development and differentiation as well as
      conceptus implantation. In addition, enJSRVs are expressed during fetal ontogeny
      leading to the apparent tolerance of sheep towards the pathogenic JSRV. Thus, the
      sheep/enJSRVs system is a model that can be utilized to study many different
      aspects of ERVs and retrovirus biology. The impressive technologies developed to
      study the sheep reproductive biology, in conjunction with the knowledge gained on
      the molecular biology of enJSRVs, makes the ovine system an ideal model to design
      experiments that can functionally address the role of ERVs in mammalian
      physiology.

PMID- 14718614
TI  - Limited infection without evidence of replication by porcine endogenous
      retrovirus in guinea pigs.
AB  - Porcine endogenous retrovirus (PERV) may potentially be transmitted through
      porcine xenotransplantation products administered to humans. This study examined
      the feasibility of using guinea pigs as a model to characterize the in vivo
      infectivity of PERV. To enhance the susceptibility of guinea pigs to retroviral
      infection or genomic integration, moderate physiological or immunological changes
      were induced prior to exposing the animals to PERV. Quantitative PERV-specific
      PCR performed on all tested samples resulted in either undetectable or very low
      copy numbers of proviruses, even in animals possessing PERV-specific antibody
      responses. The low copy number of viral DNA detected suggests that PERV infected
      a limited number of cells. However, PERV DNA levels did not increase over time,
      suggesting no virus replication occurred. These results in the guinea pig are
      similar to previous observations of non-human primate cells that allow PERV
      infection but do not support PERV replication in vitro.

PMID- 14718615
TI  - A novel simian immunodeficiency virus isolated from a Schmidt's guenon
      (Cercopithecus ascanius schmidti).
AB  - A novel simian immunodeficiency virus (SIV) was characterized from a Schmidt's
      guenon (Cercopithecus ascanius schmidti), which was housed in a local zoo. The
      virus infection was detected during a routine serological screening for
      antibodies that were cross-reactive with SIVmac antigens. Infection with an
      immunodeficiency virus was confirmed using an INNO-LIA HIV Confirmation assay.
      Using DNA isolated from a blot clot, a 1895 nt partial pol sequence was amplified
      and sequenced. Phylogenetic analysis showed that this virus, designated SIVschm,
      shares a distant relationship with SIVgsn, isolated from greater spot-nosed
      monkeys, and is one of the most divergent SIVs identified to date.

PMID- 14718616
TI  - Simian T cell leukaemia virus type I subtype B in a wild-caught gorilla (Gorilla
      gorilla gorilla) and chimpanzee (Pan troglodytes vellerosus) from Cameroon.
AB  - A serological survey for human T cell leukaemia virus (HTLV)/simian T cell
      leukaemia virus (STLV) antibodies was performed in 61 wild-caught African apes,
      including five gorillas and 56 chimpanzees originating from south Cameroon. Two
      young animals, a gorilla (Gorilla gorilla gorilla) and a chimpanzee (Pan
      troglodytes vellerosus), exhibited a pattern of complete HTLV-I seroreactivity.
      Sequence comparison and phylogenetic analyses using the complete LTR (750 bp) and
      a 522 bp fragment of the env gene indicated the existence of two novel STLV-I
      strains, both of which belonged to HTLV-I/STLV-I molecular clade subtype B,
      specific to central Africa. These first STLV-I strains to be characterized in
      gorilla and chimpanzee were closely related to each other as well as to several
      HTLV-I strains originating from inhabitants of south Cameroon, including pygmies.
      Such findings reinforce the hypothesis of interspecies transmission of STLV-I to
      humans, leading to the present day distribution of HTLV-I in central African
      inhabitants.

PMID- 14718617
TI  - Evidence of intratypic recombination in natural populations of hepatitis C virus.
AB  - Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at
      least six different types and an increasing number of subtypes have been
      reported. Genotype 1 is the most prevalent genotype found in South America. In
      the present study, three different genomic regions (5'UTR, core and NS5B) of four
      HCV strains isolated from Peruvian patients were sequenced in order to
      investigate the congruence of HCV genotyping for these three genomic regions.
      Phylogenetic analysis using 5'UTR-core sequences found strain PE22 to be related
      to subtype 1b. However, the same analysis using the NS5B region found it to be
      related to subtype 1a. To test the possibility of genetic recombination,
      phylogenetic studies were carried out, revealing that a crossover event had taken
      place in the NS5B protein. We discuss the consequences of this observation on HCV
      genotype classification, laboratory diagnosis and treatment of HCV infection.

PMID- 14718618
TI  - Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection.
AB  - Hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) genome was directly
      sequenced from 12 chronically infected patients who had not responded to
      interferon (IFN) treatment. Due to the quasispecies nature of HCV circulating
      genomes, serum samples from four patients showing different evolutionary
      characteristics were further analysed. Serial samples from each patient were
      taken before, soon after and 14-23 months after a 6 month IFN treatment. HVR1
      from each sample was amplified, cloned and the clones sequenced. For each
      patient, a phylogenetic analysis of the clones was performed and quasispecies
      complexity and genetic distances were calculated. The amino acid sequences and
      predicted antigenic profiles were analysed. The pre-treatment samples of the
      different patients presented dissimilar genetic quasispecies composition. For
      three of the patients, we showed that, regardless of the complexity or diversity
      of the viral populations before treatment, they evolved towards genetic
      diversification following selective pressure. Once the environment became stable,
      the entire population tended towards homogeneity. The fourth patient represented
      a case where different components of the quasispecies coexisted for long periods
      without replacement. We propose herein that the evolution of HVR1 of E2 is more
      likely to be directed by selection of clearly different subpopulations
      (modification of quasispecies equilibrium) than by a continuous mechanism related
      to the successive accumulation of point mutations. The prevalence of a
      quasispecies shift mechanism was revealed by the cloning analysis during the
      follow-up period of the evolutionary process.

PMID- 14718619
TI  - Infection of primary human macrophages with hepatitis C virus in vitro: induction
      of tumour necrosis factor-alpha and interleukin 8.
AB  - Hepatitis C virus (HCV) has been reported to replicate in monocytes/macrophages
      in infected patients. However, it is unclear whether macrophages are susceptible
      to infection in vitro and whether such an infection is consequential. Sera from
      26 HCV-infected patients were incubated with primary human macrophages collected
      from healthy donors. Virus negative strand was detected by a Tth enzyme-based
      strand-specific assay and virus sequences were analysed by single strand
      conformation polymorphism (SSCP) and sequencing. Concentrations of the cytokines
      tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-8,
      IL-10 and IL-12p70 were measured in culture supernatants and respective mRNAs
      were analysed in cell extracts by quantitative RT-PCR. For 15 sera, HCV RNA was
      detectable in 2- and 3-week cultures from at least one donor. Virus negative
      strand was detected in 29 % of macrophage samples in this group. In four cases,
      HCV RNA sequences amplified from macrophages differed from those amplified from
      sera suggesting evolution during infection. Concentrations of TNF-alpha and IL-8
      were found to be significantly higher in supernatants from HCV-infected cultures.
      In conclusion, these preliminary data suggest that primary human macrophages are
      susceptible to HCV infection in vitro and this infection is associated with the
      induction of cytokines TNF-alpha and IL-8.

PMID- 14718620
TI  - Studies of genetically defined chimeras of a European type A virus and a South
      African Territories type 2 virus reveal growth determinants for foot-and-mouth
      disease virus.
AB  - The three South African Territories (SAT) types of foot-and-mouth disease virus
      (FMDV) display great genetic and antigenic diversity, resulting from the
      independent evolution of these viruses in different geographical localities. For
      effective control of the disease in such areas, the use of custom-made vaccines
      is required. To circumvent the tedious process of vaccine strain selection, an
      alternative in the control process is being investigated. Specifically, it is
      proposed to replace the antigenic determinants of an infectious genome-length
      cDNA copy of a good SAT vaccine strain with those of appropriate field strains,
      producing custom-made FMDV chimeras for use in vaccine production. Here the
      construction of an infectious genome-length cDNA copy of the SAT2 vaccine strain,
      ZIM/7/83, is described, created utilizing an exchange-cassette strategy with an
      existing A(12) genome-length cDNA clone. The virus derived from this cDNA
      (designated vSAT2) displayed excellent growth properties in cell culture,
      indicating its potential usefulness in the production of custom-made vaccine
      strains. Evaluation of the growth of various SAT2/A12 chimeras created during the
      derivation of SAT2 infectious cDNA suggested incompatibilities between the non
      structural proteins of ZIM/7/83 and the 5' UTR of A(12).

PMID- 14718621
TI  - A murine oral enterovirus 71 infection model with central nervous system
      involvement.
AB  - Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot
      and-mouth disease or herpangina to fatal meningoencephalitis complicated with
      neurogenic pulmonary oedema. Its pathogenesis, especially the CNS involvement, is
      not clearly understood. The aim of this study was to set up a mouse EV71
      infection model with CNS involvement. EV71 virus was administrated orally to
      neonatal mice. The EV71-infected mice manifested a skin rash at an early stage
      and hind limb paralysis or death at a later stage. Immunohistochemical staining
      and virus isolation demonstrated that EV71 replicated in the small intestine,
      induced viraemia and spread to various organs. Kinetic studies showed that EV71
      antigen was first detected in the intestine at 6 h, in the thoracic spinal cord
      at 24 h, in the cervical spinal cord at 50 h and in the brain stem at 78 h post
      infection. Leukocyte infiltration was evident in the spinal cord and brain stem.
      Furthermore, EV71 virus could be transmitted to littermates within the same cage.

PMID- 14718622
TI  - Laboratory efforts to cultivate noroviruses.
AB  - Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide and are
      recognized as the foremost cause of foodborne illness. Despite numerous efforts,
      routine cell cultures have failed to yield replicating NoV. This paper describes
      methods used to try to grow NoV in vitro in two laboratories. Cells (A549, AGS,
      Caco-2, CCD-18, CRFK, CR-PEC, Detroit 551, Detroit 562, FRhK-4, HCT-8, HeLa, HEC,
      HEp-2, Ht-29, HuTu-80, I-407, IEC-6, IEC-18, Kato-3, L20B, MA104, MDBK, MDCK, RD,
      TMK, Vero and 293) were cultured on solid or permeable surfaces. Differentiation
      was induced using cell culture supplements such as insulin, DMSO and butyric
      acid. In some cases, the cells and the NoV-containing stool samples were treated
      with bioactive digestive additives. Variables evaluated in cultivation
      experiments included the method of preparation of the virus inoculum, the
      genotype of the virus, conditions for maintenance of cell monolayers, additives
      in the maintenance medium and the method of inoculation of the cells. Serial
      blind passage studies were performed routinely. In addition to evaluation for
      CPE, evidence of virus replication was sought using immunofluorescent assays to
      detect newly produced viral capsid antigen and RT-PCR assays to detect the viral
      genome. Although some infected cultures remained NoV positive by RT-PCR for up to
      five passages and an occasional cell in a monolayer showed evidence of specific
      immunofluorescence, no reproducible NoV-induced CPE was observed and all RT-PCR
      results that were positive initially were negative following continued passaging.
      Thus, attempts to develop a method for the cultivation of NoV were unsuccessful.

PMID- 14718623
TI  - Identification of a new strain of hepatitis E virus from an outbreak in Namibia
      in 1995.
AB  - Endemic circulation of hepatitis E virus (HEV) in Namibia was suspected from
      serological data during an outbreak of non-A, non-B hepatitis in Rundu in 1995.
      The source of the outbreak was suspected to be the water supply, which had been
      compromised approximately 6 months earlier. Four HEV isolates from four different
      persons in this outbreak were successfully amplified, sequenced and analysed over
      a 451 bp region of a subgenomic fragment from the 3' end of the genome in ORF2.
      Phylogenetic analysis showed that the four Namibian HEV isolates clustered with a
      Mexican isolate in genotype II and shared 85.8-86.3 % nucleotide identity with
      the 1987 Mexican isolate, but were only 77.6-79.6 % similar to other African
      isolates. HEV isolated from the same region of Namibia in 1983 was reported to
      cluster in genotype I. However, virus isolates from sporadic cases of HEV
      isolated in 1997/8 in Nigeria were also from genotype II.

PMID- 14718625
TI  - Poxvirus genomes: a phylogenetic analysis.
AB  - The evolutionary relationships of 26 sequenced members of the poxvirus family
      have been investigated by comparing their genome organization and gene content
      and by using DNA and protein sequences for phylogenetic analyses. The central
      region of the genome of chordopoxviruses (ChPVs) is highly conserved in gene
      content and arrangement, except for some gene inversions in Fowlpox virus (FPV)
      and species-specific gene insertions in FPV and Molluscum contagiosum virus
      (MCV). In the central region 90 genes are conserved in all ChPVs, but no gene
      from near the termini is conserved throughout the subfamily. Inclusion of two
      entomopoxvirus (EnPV) sequences reduces the number of conserved genes to 49. The
      EnPVs are divergent from ChPVs and between themselves. Relationships between ChPV
      genera were evaluated by comparing the genome size, number of unique genes, gene
      arrangement and phylogenetic analyses of protein sequences. Overall, genus
      Avipoxvirus is the most divergent. The next most divergent ChPV genus is
      Molluscipoxvirus, whose sole member, MCV, infects only man. The Suipoxvirus,
      Capripoxvirus, Leporipoxvirus and Yatapoxvirus genera cluster together, with
      Suipoxvirus and Capripoxvirus sharing a common ancestor, and are distinct from
      the genus Orthopoxvirus (OPV). Within the OPV genus, Monkeypox virus, Ectromelia
      virus and Cowpox virus strain Brighton Red (BR) do not group closely with any
      other OPV, Variola virus and Camelpox virus form a subgroup, and Vaccinia virus
      is most closely related to CPV-GRI-90. This suggests that CPV-BR and GRI-90
      should be separate species.

PMID- 14718624
TI  - Genetic changes in hepatitis E virus of subtype 1a in patients with sporadic
      acute hepatitis E in Kathmandu, Nepal, from 1997 to 2002.
AB  - To investigate the genetic changes in hepatitis E virus (HEV) strains in the
      Kathmandu valley of Nepal, we compared the 412 nt sequence within open reading
      frame 2 of HEV among HEV isolates recovered from 16 patients in 1999, 14 patients
      in 2000 and 38 patients in 2002, and additional isolates recovered from 48
      patients in 1997 whose nucleotide sequences have been previously published. All
      116 HEV-viraemic samples were genotyped as 1 and subtyped further as 1a (n=85, 73
      %), 1c (n=29, 25 %) and mixed infection of 1a and 1c (n=2, 2 %): subtype 1c was
      detected only in 1997. Among the 1a isolates, nucleotide sequence identity with
      the representative 1a isolate of Ne131-1997 was 96.4+/-2.4 % (mean+/-SD) in 1997,
      93.9+/-1.7 % in 1999, 92.2+/-1.0 % in 2000 and 91.7+/-0.5 % in 2002, indicating
      gradual diversification of HEV sequences. When phylogenetic analysis of the 87
      subtype 1a isolates was performed, they further segregated into five clusters,
      with two predominant clusters of 1a-2 and 1a-3: the annual frequency of cluster
      1a-2 isolates decreased from 63 % in 1997, to 50 % in 1999, to 7 % in 2000 and no
      cases in 2002; cluster 1a-3 isolates were observed in all four years and its
      annual frequency increased from 5 % in 1997 to 95 % in 2002. Of the remaining
      three clusters, cluster 1a-1 was detectable only in 1997 and clusters 1a-4 and 1a
      5 emerged in 2000 and 2002, respectively. These results indicate that genetic
      changes and take over of HEV strains may contribute to the genetic variability of
      HEV in the community.

PMID- 14718626
TI  - The CD2v protein of African swine fever virus interacts with the actin-binding
      adaptor protein SH3P7.
AB  - The predicted extracellular domain of the CD2v protein of African swine fever
      virus (ASFV) shares significant similarity to that of the CD2 protein in T cells
      but has a unique cytoplasmic domain of unknown function. Here we have shown that
      CD2v is expressed as a glycoprotein of approximately 105 kDa in ASFV-infected
      cells. In the absence of an extracellular ligand, the majority of CD2v appears to
      localize to perinuclear membrane compartments. Furthermore, we have shown using
      the yeast two-hybrid system and by direct binding studies that the cytoplasmic
      tail of CD2v binds to the cytoplasmic adaptor protein SH3P7 (mAbp1, HIP55), which
      has been reported to be involved in diverse cellular functions such as vesicle
      transport and signal transduction. A cDNA clone encoding a variant form of SH3P7
      could also be identified and was found to be expressed in a wide range of porcine
      tissues. Deletion mutagenesis identified proline-rich repeats of sequence PPPKPC
      in the ASFV CD2v protein to be necessary and sufficient for binding to the SH3
      domain of SH3P7. In ASFV-infected cells, CD2v and SH3P7 co-localized in areas
      surrounding the perinuclear virus factories. These areas also stained with an
      antibody that recognizes a Golgi network protein, indicating that they contained
      membranes derived from the Golgi network. Our data provide a first molecular
      basis for the understanding of the immunomodulatory functions of CD2v in ASFV
      infected animals.

PMID- 14718627
TI  - Protection against wild-type murine gammaherpesvirus-68 latency by a latency
      deficient mutant.
AB  - A murine gammaherpesvirus-68 (MHV-68) mutant with deregulated transcription of
      its ORF50 transactivator was severely impaired in latency establishment. The
      deregulated virus showed reduced immunogenicity, probably reflecting a lower
      antigen load. However, it still elicited effective immunity to a subsequent wild
      type (WT) virus challenge. Infection was not completely prevented, but was very
      substantially reduced in extent and the long-term level of WT viral DNA in lungs
      and spleens remained low. Thus latency-deficient MHV-68 illustrates a possible
      general approach to creating attenuated gammaherpesvirus vaccines that can
      protect against pathogenic WT infections.

PMID- 14718628
TI  - Forced lytic replication impairs host colonization by a latency-deficient mutant
      of murine gammaherpesvirus-68.
AB  - A regulated switch between latent and lytic gene expression is common to all
      known herpesviruses. However, the effects on host colonization of altering this
      switch are largely unknown. We deregulated the transcription of the gene encoding
      the major lytic transactivator of murine gammaherpesvirus-68, ORF50, by inserting
      a new and powerful promoter element in its 5' untranslated region. In vitro, the
      mutant virus (M50) transcribed ORF50 at a high level and showed more rapid lytic
      spread in permissive fibroblast cultures, but in vivo, the M50 virus showed a
      severe deficit in latency establishment, with no sign of the infectious
      mononucleosis-like illness normally associated with wild-type infection. Although
      a low level of M50 viral DNA was detectable by PCR in spleens, replication
      competent virus could not be recovered beyond 10 days post-infection. The M50
      virus was also attenuated in immunocompromised mice. Thus a gammaherpesvirus
      unable to shut off lytic cycle gene expression showed severely restricted host
      colonization.

PMID- 14718629
TI  - The herpesvirus saimiri ORF73 gene product interacts with host-cell mitotic
      chromosomes and self-associates via its C terminus.
AB  - The herpesvirus saimiri (HVS) ORF73 gene product shares limited homology with the
      ORF73 protein of Kaposi's sarcoma-associated herpesvirus (KSHV). ORF73 is
      expressed in an in vitro model of HVS latency, where the genome persists as a non
      integrated circular episome. This suggests it may have a similar role to KSHV
      ORF73 in episomal maintenance, by tethering viral genomes to host-cell
      chromosomes. Here, the association of ORF73 with host mitotic chromosomes is
      described. Deletion analysis demonstrates that the distal 123 aa of the ORF73
      protein are required for mitotic chromosomal localization and for self
      association. Moreover, deletion of the extreme C terminus disrupts both self
      association and host mitotic chromosome colocalization. This suggests that HVS
      ORF73 has a similar role to KSHV ORF73 in episomal maintenance and that
      association of ORF73 to host mitotic chromosomes is dependent on its ability to
      form multimers.

PMID- 14718631
TI  - Identification of the nuclear localization signals within the Epstein-Barr virus
      EBNA-6 protein.
AB  - Epstein-Barr virus nuclear antigen (EBNA)-6 is essential for EBV-induced
      immortalization of primary human B-lymphocytes in vitro. Previous studies have
      shown that EBNA-6 acts as a transcriptional regulator of viral and cellular
      genes; however at present, few functional domains of the 140 kDa EBNA-6 protein
      have been completely characterized. There are five computer-predicted nuclear
      localization signals (NLS), four monopartite and one bipartite, present in the
      EBNA-6 amino acid sequence. To identify which of these NLS are functional, fusion
      proteins between green fluorescent protein and deletion constructs of EBNA-6 were
      expressed in HeLa cells. Each of the constructs containing at least one of the
      NLS was targeted to the nucleus of cells whereas a construct lacking all of the
      NLS was cytoplasmic. Site-directed mutation of these NLS demonstrated that only
      three of the NLS were functional, one at the N-terminal end (aa 72-80), one in
      the middle (aa 412-418) and one at the C-terminal end (aa 939-945) of the EBNA-6
      protein.

PMID- 14718630
TI  - Genotypic characterization of Kaposi's sarcoma-associated herpesvirus in
      asymptomatic infected subjects from isolated populations.
AB  - Molecular epidemiological studies of Kaposi's sarcoma-associated herpesvirus
      (KSHV) have concentrated on characterization of viral strains in tumour biopsy
      samples from Kaposi's sarcoma (KS) patients, mostly obtained in the United States
      and Europe. Tumour biopsies are a convenient source of viral DNA, as they have a
      high viral load compared to peripheral blood. However, sequences obtained from
      biopsies may not be representative of viral strains in asymptomatic subjects and
      information on ethnicity is often not available. Here, a population-based
      approach has been used to study the molecular and seroepidemiology of KSHV in
      isolated populations in Ecuador and Botswana. Amerindians in Ecuador had a
      variable prevalence of KSHV and all strains characterized were of subtype E,
      based on K1 sequencing. All Amerindian strains had predominant (P)-type K15
      alleles and had sequences in both T0.7 and ORF 75 that appeared to be
      characteristic of these strains. The prevalence of KSHV in two ethnic groups in
      Botswana was extremely high. K1 sequences from both Bantu and San subjects were
      mostly of subtypes B and A5, which are typical of African KSHV strains, but the
      sequence from one San subject did not cluster with any known subtype.
      Considerable heterogeneity was seen in the T0.7 and ORF 75 genes in the San
      subjects and one had a minor (M)-type K15 allele. The heterogeneity of the KSHV
      strains found in these subjects from Botswana contrasts with the homogeneity of
      KSHV strains in Amerindians, reflecting differences in the evolutionary history
      of these populations.

PMID- 14718632
TI  - Resistance to pseudorabies virus infection in transformed cell lines expressing a
      soluble form of porcine herpesvirus entry mediator C.
AB  - Porcine herpesvirus entry mediator C (HveC) is an alphaherpesvirus receptor that
      binds to virion glycoprotein D (gD). Porcine HveC mediates entry of pseudorabies
      virus (PRV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and bovine
      herpesvirus type 1 (BHV-1). In order to assess the antiviral potential of a
      soluble form of porcine HveC, Vero cells were transformed with the chimeric gene
      expressing a fusion protein (PHveCIg) consisting of an extracellular domain of
      porcine HveC and the Fc portion of human IgG1. The transformed cell lines
      expressing PHveCIg showed marked resistance to PRV infection. Resistance to
      infection by other alphaherpesviruses (HSV-1 and BHV-1) was also observed in the
      transformed cell line. The present results demonstrate that a soluble form of
      porcine HveC is able to exert a significant antiviral effect against pseudorabies
      virus and other alphaherpesvirus infection in vitro.

PMID- 14718633
TI  - Inhibition of human cytomegalovirus replication by small interfering RNAs.
AB  - Small interfering RNAs (siRNAs) are the mediators of a sequence-specific process
      of gene silencing called RNA interference (RNAi). Here, we show that synthetic
      siRNAs against essential gene products of human cytomegalovirus (HCMV) can
      trigger RNAi in serum-starved, infected primary fibroblasts, as well as in U373
      cells, leading to effective inhibition of viral DNA replication. This opens new
      possibilities for antiviral strategies and for the analysis of viral and cellular
      genes important to HCMV physiology.

PMID- 14718634
TI  - Precursor of human adenovirus core polypeptide Mu targets the nucleolus and
      modulates the expression of E2 proteins.
AB  - We have examined the subcellular localization properties of human adenovirus 2
      (HAdV-2) preMu and mature Mu (pX) proteins as fusions with enhanced green
      fluorescence protein (EGFP). We determined that preMu is exclusively a nucleolar
      protein with a single nucleolar accumulation signal within the Mu sequence. In
      addition, we noted that both preMu-EGFP and Mu-EGFP are excluded from adenovirus
      DNA-binding protein (DBP)-rich replication centres in adenovirus-infected cells.
      Surprisingly, we observed that cells in which preMu-EGFP (but not Mu-EGFP) is
      transiently expressed prior to or shortly after infection with Ad2 did not
      express late adenovirus genes. Further investigation suggested this might be due
      to a failure to express pre-terminal protein (preTP) from the E2 region, despite
      expression of another E2 protein, DBP. Deletion mutagenesis identified a highly
      conserved region in the C terminus of preMu responsible for these observations.
      Thus our data suggest that preMu may play a role in modulating accumulation of
      proteins from the E2 region.

PMID- 14718635
TI  - Application of maximum-likelihood models to selection pressure analysis of group
      I nucleopolyhedrovirus genes.
AB  - Knowledge of virus genes under positive selection pressure can help identify
      molecular determinants of species-specific virulence or host range without prior
      knowledge of the mechanisms governing host range and virulence. Towards this end,
      codon-based models of substitution were used in a maximum-likelihood approach to
      analyse selection pressures acting on 83 genes of group I nucleopolyhedroviruses
      (NPVs). Evidence for positive selection was found for nine genes: ac38, ac66,
      arif-1, lef-7, lef-10, lef-12, odv-e18, odv-e56 and vp80. The baculovirus DNA
      helicase gene (dnahel) was not found to be positively selected using models that
      allowed the intensity of selection pressure to vary among codon sites. Further
      analysis with a method that allows selection pressure intensity to vary among
      lineages suggests that positive selection may have occurred in dnahel during the
      divergence of Bombyx mori NPV and the NPVs of Autographa californica and
      Rachiplusia ou. NPV genes that have undergone positive selection may modulate the
      ability of different NPVs to replicate efficiently in cells (lef-7, lef-10, lef
      12) or to establish primary infection of the midgut (odv-e18, odv-e56) of
      different host species.

PMID- 14718636
TI  - The gp64 locus of Anticarsia gemmatalis multicapsid nucleopolyhedrovirus contains
      a 3' repair exonuclease homologue and lacks v-cath and ChiA genes.
AB  - Anticarsia gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV) is one of the
      most successful biological insecticides. In this study, we cloned and sequenced a
      12.5 kbp BamHI-D restriction endonuclease fragment of the AgMNPV isolate 2D
      genome that includes the gp64 gene. We compared this highly conserved region with
      that of other baculoviruses. AgMNPV contained two genes, p22.2 and v-trex, in
      common with Choristoneura fumiferana MNPV (CfMNPV) that were not present in other
      baculoviruses. The v-trex gene has homology to a eukaryotic 3' repair exonuclease
      and appears to have been acquired from an invertebrate host. The v-trex gene
      product has the potential to be involved in virus recombination or UV-light
      tolerance. Multigene phylogenetic analysis suggested that AgMNPV is most closely
      related to Orgyia pseudotsugata MNPV (OpMNPV). AgMNPV differed from other group I
      NPVs in that ChiA and v-cath gene homologues were missing from the region
      downstream of the gp64 gene. Proteinase assays and genetic probes suggest the v
      cath gene is absent from AgMNPV.

PMID- 14718637
TI  - The C-terminal 33 amino acids of the cucumber mosaic virus 3a protein affect
      virus movement, RNA binding and inhibition of infection and translation.
AB  - The capsid protein (CP) of Cucumber mosaic virus (CMV) is required for cell-to
      cell movement, mediated by the 3a movement protein (MP). Deletion of the C
      terminal 33 amino acids of the CMV 3a MP (in the mutant designated 3aDeltaC33 MP)
      resulted in CP-independent cell-to-cell movement, but not long-distance movement.
      RNA-binding studies done in vitro using isolated bacterially expressed MP showed
      that the 3aDeltaC33 MP bound RNA more strongly, with fewer regions sensitive to
      RNase and formed cooperatively bound complexes at lower ratios of protein : RNA
      than the wild-type (wt) 3a MP. Analysis of the architecture of the complexes by
      atomic force microscopy showed that the wt 3a MP formed a single type of complex
      with RNA, resembling beads on a string. By contrast, the 3aDeltaC33 MP formed
      several types of complexes, including complexes with virtually no MP bound or
      thicker layers of MP bound to the RNA. Assays showed that protein-RNA complexes
      containing high levels of either MP inhibited the infectivity and in vitro
      translatability of viral RNAs. The 3aDeltaC33 MP inhibited these processes at
      lower ratios of protein : RNA than the wt 3a MP, consistent with its stronger
      binding properties. The apparent contradiction between these inhibition data and
      the CP-independent cell-to-cell movement of CMV expressing the 3aDeltaC33 MP is
      discussed.

PMID- 14718638
TI  - Efficient translation of alfamovirus RNAs requires the binding of coat protein
      dimers to the 3' termini of the viral RNAs.
AB  - The coat protein (CP) of Alfalfa mosaic virus (AMV) is required to initiate
      infection by the viral tripartite RNA genome whereas infection by the tripartite
      Brome mosaic virus (BMV) genome is independent of CP. AMV CP stimulates
      translation of AMV RNA in vivo 50- to 100-fold. The 3' untranslated region (UTR)
      of the AMV subgenomic CP messenger RNA 4 contains at least two CP binding sites.
      A CP binding site in the 3'-terminal 112 nucleotides of RNA 4 was found to be
      required for efficient translation of the RNA whereas an upstream binding site
      was not. Binding of CP to the AMV 3' UTR induces a conformational change of the
      RNA but this change alone was not sufficient to stimulate translation. CP mutant
      R17A is unable to bind to the 3' UTR and translation in vivo of RNA 4 encoding
      this mutant occurs at undetectable levels. Replacement of the 3' UTR of this
      mutant RNA 4 by the 3' UTR of BMV RNA 4 restored translation of R17A-CP to wild
      type levels. Apparently, the BMV 3' UTR stimulates translation independently of
      CP. AMV CP mutant N199 is defective in the formation of CP dimers and did not
      stimulate translation of RNA 4 in vivo although the mutant CP did bind to the 3'
      UTR. The finding that N199-CP does not promote AMV infection corroborates the
      notion that the requirement of CP in the inoculum reflects its role in
      translation of the viral RNAs.

PMID- 14718639
TI  - Expression of functionally active helper component protein of Tobacco etch
      potyvirus in the yeast Pichia pastoris.
AB  - Tobacco etch potyvirus (TEV) is transmitted by aphids in a non-persistent manner
      with the assistance of a virus-encoded protein known as helper component (HC
      Pro). To produce a biologically active form of recombinant TEV HC-Pro protein,
      heterologous expression in the methylotrophic yeast Pichia pastoris was used. A
      cDNA encoding the TEV HC-Pro region, fused to a Saccharomyces cerevisiae alpha
      mating factor secretory peptide coding region, was inserted into the P. pastoris
      genome using a modified version of the pPIC9 vector. The expressed TEV HC-Pro
      protein was obtained directly from culture medium of recombinant yeast colonies;
      it was able to interact with TEV particles in a protein overlay binding assay,
      and also to assist aphid transmission of purified TEV particles to plants using
      the aphid Myzus persicae as vector. Our results indicate that P. pastoris
      provides a rapid and low-cost heterologous expression system that can be used to
      obtain biologically active potyvirus HC-Pro protein for in vitro transmission
      assays.

PMID- 14718640
TI  - Arg-16 and Arg-21 in the N-terminal region of the triple-gene-block protein 1 of
      Bamboo mosaic virus are essential for virus movement.
AB  - The protein encoded by the first gene of the triple gene block (TGBp1) of
      potexviruses is required for movement of the viruses. It has been reported that
      single Arg-->Ala substitutions at position 11, 16 or 21 of TGBp1 of Bamboo mosaic
      virus (BaMV) eliminate its RNA-binding activity, while substitutions at position
      16 or 21 only affect its NTPase activity (Liou et al., Virology 277, 336-344,
      2000). However, it remains unclear whether these Arg-->Ala substitutions also
      affect the movement of BaMV in plants. To address this question, six mutants of
      BaMV, each containing either a single- or a double-alanine substitution at Arg
      11, Arg-16 and Arg-21 of TGBp1, were constructed and used to infect Chenopodium
      quinoa and Nicotiana benthamiana. We found that all of the BaMV mutants were able
      to replicate in protoplasts of N. benthamiana. However, only the mutant with an
      Arg-11-->Ala substitution in TGBp1 remained capable of movement from cell to cell
      in plants. Mutants with Arg-16, Arg-21 or both Arg-16 and Arg-21 of TGBp1
      replaced with alanine were defective in virus movement. This defect was
      suppressed when a wild-type TGBp1 allele was co-introduced into the cells using a
      novel satellite replicon. The ability to trans-complement the movement defect by
      the wild-type TGBp1 strongly suggests that the Arg-->Ala substitution at position
      16 or 21 of TGBp1, which diminishes the RNA-binding and NTPase activities of
      TGBp1, also eliminates the capability of BaMV to move from cell to cell in host
      plants.

PMID- 14718641
TI  - Reduced proteinase K resistance and infectivity of prions after pressure
      treatment at 60 degrees C.
AB  - High hydrostatic pressure is a mild technology compared with high temperatures
      and is commonly used for food pasteurization. Crude brain homogenates of
      terminally diseased hamsters infected with scrapie 263K strain were heated at 60
      degrees C and/or pressurized up to 1000 MPa for 2 h. Prion proteins were analysed
      for their proteinase K sensitivity using a Western blot technique. PrP(Sc)
      pressurized with 500 MPa or above proved to be proteinase K sensitive. To test
      the remaining infectivity of the pressurized material, hamsters were infected
      intracerebrally. Results showed a greatly delayed onset of disease (from 80 up to
      153 days) when samples had been pressurized at 500 MPa and above. An increase in
      the survival rate was also observed: 47 % survival over 180 days was seen
      following infection with homogenates pressurized at 700-1000 MPa.

PMID- 14718642
TI  - Delay in onset of prion disease for the HY strain of transmissible mink
      encephalopathy as a result of prior peripheral inoculation with the replication
      deficient DY strain.
AB  - We report that the replication-deficient DY strain of transmissible mink
      encephalopathy (TME) can delay disease caused by the pathogenic HY TME strain. In
      this study, competition between the HY and DY TME agents was investigated
      following superinfection of the sciatic nerve and peritoneal cavity. Initially,
      DY TME infection was examined in the absence of superinfection and it was found
      that inoculation into the brain and sciatic nerve resulted in prion disease and
      PrP(Sc) deposition in brain but not lymphoreticular tissues. Conversely,
      intraperitoneal inoculation of the DY TME agent did not result in clinical
      symptoms, DY TME agent replication or PrP(Sc) deposition 400-600 days after
      infection. These findings indicate that the DY TME agent does not replicate in
      secondary lymphoid organs and is non-pathogenic when neuroinvasion is dependent
      on prior infection of the lymphoreticular system. However, intraperitoneal
      inoculation of the DY TME agent at 60 days, but not at 30 days, prior to
      intraperitoneal inoculation of the HY TME agent resulted in an extension of the
      HY TME incubation period. Inoculation of the DY TME agent into the sciatic nerve
      at 60 days prior to intrasciatic nerve inoculation of the HY TME agent did not
      delay the incubation period of HY TME. The ability of the DY TME agent to delay
      HY TME infection following extraneural inoculation, but not neural infection,
      suggests that HY and DY TME agent competition can occur in a common replication
      site whose cellular location precedes infection of both the lymphoreticular and
      peripheral nervous systems.

PMID- 14718643
TI  - Evidence for induction of apoptosis in T cells from murine fetal thymus following
      perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes thymic
      atrophy, but the precise mechanism of such toxicity remains unresolved. The
      current study investigated the role of apoptosis in TCDD-induced thymic
      involution following perinatal exposure to TCDD. To this end, C57BL/6 pregnant
      mice were injected intraperitoneally on gestational day (GD) 14 with a single
      dose of 10 microg/kg TCDD. Analysis of the thymus on GDs 15, 16, 17, and 18, and
      on postnatal day (PD) 1, showed a remarkable reduction in thymic cellularity 3-7
      days post-TCDD exposure. TCDD treatment also caused marked changes in the
      proportions of T-cell subsets, particularly on GD 17 and GD 18 thymocytes. In
      vitro culture of thymocytes from mice exposed perinatally to TCDD showed
      increased apoptosis when compared to the controls, which peaked on day 3 post
      TCDD exposure. Triple-color staining showed that TCDD induced apoptosis in all
      four subpopulations of T cells, with the double-positive T cells undergoing the
      highest level. Moreover, increased cleavage of caspase-3 was seen when TCDD
      exposed GD 17 thymocytes were directly tested. Furthermore, apoptosis-associated
      phenotypic changes were found in thymocytes of mice perinatally exposed to TCDD,
      characterized by an increase in expression of CD3, alphabetaTCR, IL-2R, and CD44,
      and a decrease in CD4, CD8, and J11d markers. Finally, thymocytes from mice
      exposed perinatally to TCDD showed higher levels of Fas, TRAIL, and DR5 mRNA, but
      the levels of Bcl-2, Bcl-xL, and Bax were either unaltered or changed moderately.
      Taken together, these results suggest that TCDD-induced thymic atrophy following
      perinatal exposure may result, at least in part, from increased apoptosis
      mediated by death receptor pathway involving Fas, TRAIL, and DR5.

PMID- 14718644
TI  - Water permeability and TCDD-induced edema in zebrafish early-life stages.
AB  - A common response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in
      teleost embryos is blue-sac disease, characterized by pericardial and yolk-sac
      edema. The cellular and extracellular fluids of freshwater fish are hyperosmotic
      compared to the surrounding water. In order to be in osmotic balance, freshwater
      fish must maintain a barrier to minimize water entry and excrete excess water
      that passes the barrier. We hypothesized that edema observed in TCDD-exposed
      zebrafish was caused by a failure of a barrier to incoming water. As a test of
      this hypothesis, we removed the osmotic gradient that drives water entry by
      increasing the osmolarity of the surrounding water with mannitol. Abolishing the
      osmotic gradient between the interior body fluids and the water environment of
      the developing zebrafish significantly reduced both pericardial and yolk-sac
      edema. When added after edema formation had already started, mannitol only
      partially reversed pre-existing edema. An alternate hypothesis is that TCDD
      impairs water excretion, allowing water to accumulate as edema fluid. However, we
      were unable to demonstrate an alteration in kidney function: expression of early
      markers for kidney development appeared normal, and we did not observe TCDD
      induced changes in kidney filtration. An alteration in the overall shape of the
      kidney was observed, but this may be a consequence of compression by edema. In
      conclusion, TCDD exposure may inhibit the function of a permeability barrier to
      water, which is critical for maintaining osmotic balance in early development.

PMID- 14718645
TI  - Incorporation of the genetic control of alcohol dehydrogenase into a
      physiologically based pharmacokinetic model for ethanol in humans.
AB  - The assessment of the variability of human responses to foreign chemicals is an
      important step in characterizing the public health risks posed by nontherapeutic
      hazardous chemicals and the risk of encountering adverse reactions with drugs. Of
      the many sources of interindividual variability in chemical response identified
      to date, hereditary factors are some of the least understood. Physiologically
      based pharmacokinetic modeling linked with Monte Carlo sampling has been shown to
      be a useful tool for the quantification of interindividual variability in
      chemical disposition and/or response when applied to biological processes that
      displayed single genetic polymorphisms. The present study has extended this
      approach by modeling the complex hereditary control of alcohol dehydrogenase,
      which includes polygenic control and polymorphisms at two allelic sites, and by
      assessing the functional significance of this hereditary control on ethanol
      disposition. The physiologically based pharmacokinetic model for ethanol
      indicated that peak blood ethanol levels and time-to-peak blood ethanol levels
      were marginally affected by alcohol dehydrogenase genotypes, with simulated
      subjects possessing the B2 subunit having slightly lower peak blood ethanol
      levels and shorter times-to-peak blood levels compared to subjects without the B2
      subunit. In contrast, the area under the curve (AUC) of the ethanol blood decay
      curve was very sensitive to alcohol dehydrogenase genotype, with AUCs from any
      genotype including the ADH1B2 allele considerably smaller than AUCs from any
      genotype without the ADH1B2 allele. Furthermore, the AUCs in the ADH1C1/C1
      genotype were moderately lower than the AUCs from the corresponding ADH1C2/C2
      genotype. Moreover, these simulations demonstrated that interindividual
      variability of ethanol disposition is affected by alcohol dehydrogenase and that
      the degree of this variability was a function of the ethanol dose.

PMID- 14718646
TI  - Combined screening of thymocytes using apoptosis-specific cDNA array and promoter
      analysis yields novel gene targets mediating TCDD-induced toxicity.
AB  - We have used pathway-specific cDNA arrays coupled with analysis of gene promoter
      regions to identify novel genes that may mediate the toxic effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in the thymus. C57BL/6 mice were injected ip
      with 50 microg/kg TCDD, and 3, 6, or 24 h later, RNA was extracted from the
      thymus and subjected to microarray analysis. Several members of the TNF and TNFR
      family were induced following TCDD exposure, including receptor/ligand pairs
      Ltbeta-R/LIGHT, OX40/OX40L and TNF-alpha/TNFR1. In addition, Fas and CD30 were
      also upregulated. Pro-apoptotic bcl-2 gene family members Bax and Hrk, among
      others, were also induced, as were pro-survival bcl-2 family genes Bcl-x and Bcl
      w. Cell-cycle regulator p21Cip1 was also induced. In addition, we analyzed the
      promoter regions of genes induced by TCDD for the presence of dioxin-responsive
      elements (DREs). The Fas and LIGHT gene promoters were found to contain DREs as
      analyzed by Matinspector Web-based search algorithm. Furthermore, binding of the
      aryl hydrocarbon receptor (AhR) to the DREs present on these genes was confirmed
      by chromatin immunoprecipitation. Given that several of the genes, including Fas,
      LIGHT, and CD30 are involved in negative selection of T cells in the thymus, our
      studies suggest that TCDD-induced upregulation of these genes may enhance
      negative selection leading to thymic atrophy.

PMID- 14718647
TI  - Genotoxic and antiapoptotic effect of nicotine on human gingival fibroblasts.
AB  - Growing evidence suggests that nicotine, the addictive component of cigarettes,
      can have a direct role in tumor development by enhancing cell proliferation and
      impairing apoptotic process in certain types of human cancer cell lines. Since
      the correlation between apoptosis and DNA damage is already well documented, we
      investigated the response of human gingival fibroblasts (HGFs) to nicotine
      exposure by examining its effect on DNA damage induction and apoptotic process in
      parallel. To assess the genotoxicity of this drug, the cytokinesis-block
      micronucleus (CBMN) test was performed. Treatment of HGFs with nicotine, at a
      concentration of 1 microM, caused a statistically significant increase of
      micronucleus (MN) frequency at the tested time intervals, while no change was
      detected in cell growth under the same conditions. Furthermore, we found that
      preincubation of HGFs with 1 microM nicotine strongly attenuated staurosporine
      (STP)-induced apoptosis. Finally, we found that cultures exposed to nicotine
      showed an increase of reactive oxygen species, as determined by increased levels
      of 2,7-dichlorofluorescein (DCF). When cells were prelabeled with N-acetyl
      cysteine (NAC), a substrate for glutathione synthesis, and catalase (CAT), the
      oxygen free radical scavenger, a significant reduction in cytogenetic damage was
      observed. Thus, for the first time, we report a concomitant genotoxic and
      antiapoptotic effect of nicotine in HGFs.

PMID- 14718648
TI  - A novel effect of dioxin: exposure during pregnancy severely impairs mammary
      gland differentiation.
AB  - Many ligands for the aryl hydrocarbon receptor (AhR) are considered endocrine
      disruptors and carcinogens, and assessment of adverse health effects in humans
      exposed to such chemicals has often focused on malignancies, including breast
      cancer. Mammary tissue contains the AhR, and inappropriate activation of the AhR
      during fetal development causes defects in mammary development that persist into
      adulthood. However, it is not known whether the extensive differentiation of
      mammary tissue that occurs during pregnancy is also sensitive to disruption by
      AhR activation. To examine this, we exposed pregnant C57Bl/6 mice to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on days 0, 7, and 14 of pregnancy. Examination
      of mammary glands on days 9, 12, and 17 of pregnancy and on the day of
      parturition showed severe defects in development, including stunted growth,
      decreased branching, and poor formation of lobular alveolar structures. This
      impaired differentiation was biologically significant, as expression of whey
      acidic protein in the gland was suppressed, and all pups born to TCDD-treated
      dams died within 24 h of birth. Analysis of circulating progesterone, prolactin,
      and estradiol suggest that hormone production was slightly impaired by
      inappropriate activation of the AhR. However, hormone levels were affected only
      very late in pregnancy. Given that the observed defects in gland development
      preceded these hormonal effects, altered hormone levels are an unlikely
      mechanistic explanation for impaired mammary development. This novel finding that
      AhR activation during pregnancy disrupts mammary gland differentiation raises
      questions about the susceptibility of mammary tissue to direct injury by
      endocrine disrupting agents and the potential for AhR-mediated signaling to
      adversely affect lactation and breast tissue development in human populations.

PMID- 14718649
TI  - Distinctive patterns of autoimmune response induced by different types of mineral
      oil.
AB  - Although mineral oils are generally considered nontoxic and have a long history
      of use in humans, the mineral oil Bayol F (incomplete Freund's adjuvant, IFA) and
      certain mineral oil components (squalene and n-hexadecane) induce lupus-related
      anti-nRNP/Sm or -Su autoantibodies in nonautoimmune mice. In the present study,
      we investigated whether medicinal mineral oils can induce other types of
      autoantibodies and whether structural features of hydrocarbons influence
      autoantibody specificity. Female 3-month-old BALB/c (16-45/group) mice each
      received an i.p. injection of pristane (C19), squalene (C30), IFA, three
      medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for
      autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas
      chromatography/mass spectrometry. IFA contained mainly C15-C25 hydrocarbons,
      whereas MO-HT and MO-S contained C20-C40, and MO-F contained C15-C40. Pristane
      and n-hexadecane were found in IFA (0.17% and 0.10% w/v, respectively) and MOs
      (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene
      IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic antibodies were common in
      mice treated with MO-F, as well as those treated with pristane, squalene, and
      IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in
      untreated/PBS, squalene-, or IFA-treated mice, suggesting that there is
      variability in the induction of anti-nRNP/Sm versus -chromatin/DNA antibodies.
      The preferential induction of anti-chromatin/ssDNA antibodies without anti
      nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of
      autoantibodies are regulated differently. Induction of autoantibodies by mineral
      oils considered nontoxic also may have pathogenetic implications in human
      autoimmune diseases.

PMID- 14718651
TI  - Formation of amyloid fibrils from fully reduced hen egg white lysozyme.
AB  - The fully reduced hen egg white lysozyme (HEWL), which is a good model of random
      coil structure, has been converted to highly organized amyloid fibrils at low pH
      by adding ethanol. In the presence of 90% (v/v) ethanol, the fully reduced HEWL
      adopts beta-sheet secondary structure at pH 4.5 and 5.0, and an alpha-to-beta
      transition is observed at pH 4.0. A red shift of the Congo red absorption
      spectrum caused by the precipitation of the fully reduced HEWL in the presence of
      90% (v/v) ethanol is typical of the presence of amyloid aggregation. EM reveals
      unbranched fibrils with a diameter of 2-5 nm and as long as 1-2 microm. The pH
      dependence of the initial structure of the fully reduced HEWL in the presence of
      90% (v/v) ethanol suggests that Asp and His residues may play an important role.

PMID- 14718650
TI  - Comparison of inflammatory and cytotoxic lung responses in mice after
      intratracheal exposure to spores of two different Stachybotrys chartarum strains.
AB  - Stachybotrys chartarum is an important toxigenic fungus that has been associated
      with respiratory disease onset in animals and humans. While it can be separated
      into macrocyclic trichothecene- and atranone-producing chemotypes based on
      secondary metabolite production, effects of spores of the two chemotypes on lungs
      are poorly understood. In this study we used bronchoalveolar lavage fluid (BALF)
      to investigate dose-response (30, 300, 3000 spores/g body weight [BW]) and time
      course (3, 6, 24, 48, 96 h post instillation [PI]) relationships in mice to
      exposure of macrocyclic trichothecene- (JS 58-17) and atranone-producing (JS 58
      06) S. chartarum strains, as well as Cladosporium cladosporioides spores. BALF
      total protein, albumin, pro-inflammatory cytokine (IL-1beta, IL-6, and tumor
      necrosis factor-alpha [TNF-alpha]), and lactate dehydrogenase (LDH)
      concentrations showed significant (p < 0.05) fungal species (S. chartarum vs. C.
      cladosporioides) and strain (58-17 vs. 58-06), spore dose and time dependent
      changes. The no adverse effect level (NOAEL) due to exposure to spores of JS 58
      17 and JS 58-06 was < 30 spores/g BW; for C. cladosporioides it was < 300
      spores/g BW. At moderate and high S. chartarum doses, BALF composition reflects
      differences in strain toxicity while at the lowest dose, BALF composition of
      either S. chartarum strain were similar. This suggests that at low spore doses,
      it is spore sequestered factors common to both strains not strain dependent
      toxins that are contributing to lung disease onset.

PMID- 14718652
TI  - An evolutionary route to xylanase process fitness.
AB  - Directed evolution technologies were used to selectively improve the stability of
      an enzyme without compromising its catalytic activity. In particular, this
      article describes the tandem use of two evolution strategies to evolve a
      xylanase, rendering it tolerant to temperatures in excess of 90 degrees C. A
      library of all possible 19 amino acid substitutions at each residue position was
      generated and screened for activity after a temperature challenge. Nine single
      amino acid residue changes were identified that enhanced thermostability. All 512
      possible combinatorial variants of the nine mutations were then generated and
      screened for improved thermal tolerance under stringent conditions. The screen
      yielded eleven variants with substantially improved thermal tolerance.
      Denaturation temperature transition midpoints were increased from 61 degrees C to
      as high as 96 degrees C. The use of two evolution strategies in combination
      enabled the rapid discovery of the enzyme variant with the highest degree of
      fitness (greater thermal tolerance and activity relative to the wild-type
      parent).

PMID- 14718653
TI  - The folding landscape of Streptomyces griseus protease B reveals the energetic
      costs and benefits associated with evolving kinetic stability.
AB  - Like most extracellular bacterial proteases, Streptomyces griseus protease B
      (SGPB) and alpha-lytic protease (alphaLP) are synthesized with covalently
      attached pro regions necessary for their folding. In this article, we
      characterize the folding free energy landscape of SGPB and compare it to the
      folding landscapes of alphaLP and trypsin, a mammalian homolog that folds
      independently of its zymogen peptide. In contrast to the thermodynamically stable
      native state of trypsin, SGPB and alphaLP fold to native states that are
      thermodynamically marginally stable or unstable, respectively. Instead, their
      apparent stability arises kinetically, from unfolding free energy barriers that
      are both large and highly cooperative. The unique unfolding transitions of SGPB
      and alphaLP extend their functional lifetimes under highly degradatory conditions
      beyond that seen for trypsin; however, the penalty for evolving kinetic stability
      is remarkably large in that each factor of 2.4-8 in protease resistance is
      accompanied by a cost of ~10(5) in the spontaneous folding rate and ~5-9
      kcal/mole in thermodynamic stability. These penalties have been overcome by the
      coevolution of increasingly effective pro regions to facilitate folding. Despite
      these costs, kinetic stability appears to be a potent mechanism for developing
      native-state properties that maximize protease longevity.

PMID- 14718654
TI  - Validation of helical tilt angles in the solution NMR structure of the Z domain
      of Staphylococcal protein A by combined analysis of residual dipolar coupling and
      NOE data.
AB  - Staphylococcal protein A (SpA) is a virulence factor from Staphylococcus aureus
      that is able to bind to immunoglobulins. The 3D structures of its immunoglobulin
      (Ig) binding domains have been extensively studied by NMR and X-ray
      crystallography, and are often used as model structures in developing de novo or
      ab initio strategies for predicting protein structure. These small three-helix
      bundle structures, reported in free proteins or Ig-bound complexes, have been
      determined previously using medium- to high-resolution data. Although the
      location and relative orientation of the three helices in most of these published
      3D domain structures are consistent, there are significant differences among the
      reported structures regarding the tilt angle of the first helix (helix 1). We
      have applied residual dipolar coupling data, together with nuclear Overhauser
      enhancement and scalar coupling data, in refining the NMR solution structure of
      an engineered IgG-binding domain (Z domain) of SpA. Our results demonstrate that
      the three helices are almost perfectly antiparallel in orientation, with the
      first helix tilting slightly away from the other two helices. We propose that
      this high-accuracy structure of the Z domain of SpA is a more suitable target for
      theoretical predictions of the free domain structure than previously published
      lower-accuracy structures of protein A domains.

PMID- 14718655
TI  - Chalcone isomerase family and fold: no longer unique to plants.
AB  - Chalcone isomerase, an enzyme in the isoflavonoid pathway in plants, catalyzes
      the cyclization of chalcone into (2S)-naringenin. Chalcone isomerase sequence
      family and three-dimensional fold appeared to be unique to plants and has been
      proposed as a plant-specific gene marker. Using sensitive methods of sequence
      comparison and fold recognition, we have identified genes homologous to chalcone
      isomerase in all completely sequenced fungi, in slime molds, and in many
      gammaproteobacteria. The residues directly involved in the enzyme's catalytic
      function are among the best conserved across species, indicating that the newly
      discovered homologs are enzymatically active. At the same time, fungal and
      bacterial species that have chalcone isomerase-like genes tend to lack the
      orthologs of the upstream enzyme chalcone synthase, suggesting a novel variation
      of the pathway in these species.

PMID- 14718656
TI  - Solution structure of a BolA-like protein from Mus musculus.
AB  - The BolA-like proteins are widely conserved from prokaryotes to eukaryotes. The
      BolA-like proteins seem to be involved in cell proliferation or cell-cycle
      regulation, but the molecular function is still unknown. Here we determined the
      structure of a mouse BolA-like protein. The overall topology is
      alphabetabetaalphaalphabetaalpha, in which beta(1) and beta(2) are antiparallel,
      and beta(3) is parallel to beta(2). This fold is similar to the class II KH fold,
      except for the absence of the GXXG loop, which is well conserved in the KH fold.
      The conserved residues in the BolA-like proteins are assembled on the one side of
      the protein.

PMID- 14718657
TI  - Nucleotide recognition in the ATP-grasp protein carbamoyl phosphate synthetase.
AB  - Synthesis of carbamoyl phosphate by carbamoyl phosphate synthetase (CPS) requires
      the coordinated utilization of two molecules of ATP per reaction cycle on
      duplicated nucleotide-binding sites (N and C). To clarify the contributions of
      sites N and C to the overall reaction, we carried out site-directed mutagenesis
      aimed at changing the substrate specificity of either of the two sites from ATP
      to GTP. Mutant design was based in part on an analysis of the nucleotide-binding
      sites of succinyl-CoA synthetases, which share membership in the ATP-grasp family
      with CPS and occur as GTP- and ATP-specific isoforms. We constructed and analyzed
      Escherichia coli CPS single mutations A144Q, D207A, D207N, S209A, I211S, P690Q,
      D753A, D753N, and F755A, as well as combinations thereof. All of the mutants
      retained ATP specificity, arguing for a lack of plasticity of the ATP sites of
      CPS with respect to nucleotide recognition. GTP-specific ATP-grasp proteins
      appear to accommodate this substrate by a displacement of the base relative to
      the ATP-bound state, an interaction that is precluded by the architecture of the
      potassium-binding loop in CPS. Analysis of the ATP-dependent kinetic parameters
      revealed that mutation of several residues conserved in ATP-grasp proteins and
      CPSs had surprisingly small effects, whereas constructs containing either A144Q
      or P690Q exerted the strongest effects on ATP utilization. We propose that these
      mutations affect proper movement of the lids covering the active sites of CPS,
      and interfere with access of substrate.

PMID- 14718658
TI  - Structural alteration of cofactor specificity in Corynebacterium 2,5-diketo-D
      gluconic acid reductase.
AB  - Corynebacterium 2,5-Diketo-D-gluconic acid reductase (2,5-DKGR) catalyzes the
      reduction of 2,5-diketo-D-gluconic acid (2,5-DKG) to 2-Keto-L-gulonic acid (2
      KLG). 2-KLG is an immediate precursor to L-ascorbic acid (vitamin C), and 2,5
      DKGR is, therefore, an important enzyme in a novel industrial method for the
      production of vitamin C. 2,5-DKGR, as with most other members of the aldo-keto
      reductase (AKR) superfamily, exhibits a preference for NADPH compared to NADH as
      a cofactor in the stereo-specific reduction of substrate. The application of 2,5
      DKGR in the industrial production of vitamin C would be greatly enhanced if NADH
      could be efficiently utilized as a cofactor. A mutant form of 2,5-DKGR has
      previously been identified that exhibits two orders of magnitude higher activity
      with NADH in comparison to the wild-type enzyme, while retaining a high level of
      activity with NADPH. We report here an X-ray crystal structure of the holo form
      of this mutant in complex with NADH cofactor, as well as thermodynamic stability
      data. By comparing the results to our previously reported X-ray structure of the
      holo form of wild-type 2,5-DKGR in complex with NADPH, the structural basis of
      the differential NAD(P)H selectivity of wild-type and mutant 2,5-DKGR enzymes has
      been identified.

PMID- 14718660
TI  - On the fundamental group of type II1 factors.
AB  - We present here a shorter version of the proof of our earlier work, showing that
      the von Neumann factor associated with the group Z(2)SL(2,Z) has trivial
      fundamental group.

PMID- 14718659
TI  - Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide
      reveals details on substrate specificity and tetrahedral intermediate formation.
AB  - Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family
      of serine proteases. DPPIV removes dipeptides from the N terminus of substrates,
      including many chemokines, neuropeptides, and peptide hormones. Specific
      inhibition of DPPIV is being investigated in human trials for the treatment of
      type II diabetes. To understand better the molecular determinants that underlie
      enzyme catalysis and substrate specificity, we report the crystal structures of
      DPPIV in the free form and in complex with the first 10 residues of the
      physiological substrate, Neuropeptide Y (residues 1-10; tNPY). The crystal
      structure of the free form of the enzyme reveals two potential channels through
      which substrates could access the active site-a so-called propeller opening, and
      side opening. The crystal structure of the DPPIV/tNPY complex suggests that
      bioactive peptides utilize the side opening unique to DPPIV to access the active
      site. Other structural features in the active site such as the presence of a Glu
      motif, a well-defined hydrophobic S1 subsite, and minimal long-range interactions
      explain the substrate recognition and binding properties of DPPIV. Moreover, in
      the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a
      tetrahedral intermediate that occurs during catalysis. Conformational changes of
      S630 and H740 between DPPIV in its free form and in complex with tNPY were
      observed and contribute to the stabilization of the tetrahedral intermediate. Our
      results facilitate the design of potent, selective small molecule inhibitors of
      DPPIV that may yield compounds for the development of novel drugs to treat type
      II diabetes.

PMID- 14718661
TI  - MLL 5 protein forms intranuclear foci, and overexpression inhibits cell cycle
      progression.
AB  - MLL5 is a mammalian trithorax group (trx-G) gene identified within chromosome
      band 7q22, a frequently deleted element found in cytogenetic aberrations of acute
      myeloid malignancies. MLL5 cDNA was linked with the FLAG and V5 tags at the N and
      C terminus, respectively, and transfected into 293T cells. Immunofluoresence
      staining of the expressed tagged MLL5 protein showed localization to the nucleus
      and exclusion from nucleoli, and no surface staining was detected. Both
      ectopically introduced and endogenous MLL5 protein displayed a speckled nuclear
      distribution. By using a series of MLL5-truncated mutants fused with enhanced
      GFP, a domain (residues 945-1,156) required for foci accumulation was identified,
      and regions containing functional nuclear localization signals were mapped.
      Ectopic overexpression of GFP-MLL5 induced cell cycle arrest in G(1) phase. This
      inhibition of cell cycle progression was indicated by delayed progression into
      nocodazole-induced mitotic arrest and was confirmed by a lack of BrdUrd
      incorporation. These findings suggest that MLL5 forms intranuclear protein
      complexes that may play an important role in chromatin remodeling and cellular
      growth suppression.

PMID- 14718662
TI  - Biography of John F. Doebley.

PMID- 14718663
TI  - Erythropoietin both protects from and reverses experimental diabetic neuropathy.
AB  - Erythropoietin (EPO) possesses generalized neuroprotective and neurotrophic
      actions. We tested the efficacy of recombinant human EPO (rhEPO) in preventing
      and reversing nerve dysfunction in streptozotocin (STZ)-induced diabetes in rats.
      Two days after STZ [60 mg/kg of body weight (b.w.), i.p.], diabetic animals were
      administered rhEPO (40 microg/kg of b.w.) three times weekly for 5 weeks either
      immediately (preventive) before or after a 5-week delay (therapeutic) after
      induction of hyperglycemia or at a lower dose (8 microg/kg of b.w. once per week)
      for 8 weeks (prolonged). Tail-nerve conduction velocities (NCV) was assessed at 5
      and 11 weeks for the preventive and therapeutic schedule, respectively. Compared
      to nondiabetic rats, NCV was 20% lower after 5 weeks in the STZ group, and this
      decrease was attenuated 50% by rhEPO. Furthermore, the reduction of Na(+),K(+)
      ATPase activity of diabetic nerves (by 55%) was limited to 24% in the rhEPO
      treated group. In the therapeutic schedule, NCV was reduced by 50% after 11 weeks
      but by only 23% in the rhEPO-treated group. rhEPO treatment attenuated the
      decrease in compound muscle action potential in diabetic rats. In addition, rhEPO
      treatment was associated with a preservation of footpad cutaneous innervation, as
      assessed by protein gene product 9.5 immunostaining. Diabetic rats developed
      alterations in mechanical and thermal nociception, which were partially reversed
      by rhEPO given either in a preventative or therapeutic manner. These observations
      suggest that administration of rhEPO or its analogues may be useful in the
      treatment of diabetic neuropathy.

PMID- 14718664
TI  - Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet
      accumulation in macrophages.
AB  - Beauveriolides I and III, isolated from the culture broth of fungal Beauveria sp.
      FO-6979, showed potent inhibitory activity of lipid droplet accumulation in
      primary mouse peritoneal macrophages. The cellular molecular target of this
      inhibitory activity was studied in macrophages. Beauveriolides I and III strongly
      inhibited the cholesteryl ester (CE) synthesis with IC(50) values of 0.78 and
      0.41 microM, respectively, without showing significant effects on the
      triacylglycerol and phospholipid synthesis. Furthermore, lysosomal cholesterol
      metabolism to CE in macrophages was inhibited by the compounds, indicating that
      the inhibition site lies within steps between cholesterol departure from the
      lysosome and CE synthesis in the endoplasmic reticulum. Therefore, acyl
      CoA:cholesterol acyltransferase (ACAT) activity in the membrane fractions
      prepared from mouse macrophages was studied, resulting in a dose-dependent
      inhibition by beauveriolides I and III with IC(50) values of 6.0 and 5.5 microM,
      respectively. Thus, we showed that the beauveriolides inhibit macrophage ACAT
      activity specifically, resulting in blockage of the CE synthesis, leading to a
      reduction of lipid droplets in macrophages. ACAT activity in the membrane
      fractions prepared from mouse liver and Caco-2 cells was also inhibited,
      indicating that the beauveriolides block both ACAT-1 and -2. Moreover,
      beauveriolides I and III exert antiatherogenic activity in both low-density
      lipoprotein receptor- and apolipoprotein E-knockout mice without any side effects
      such as diarrhea or cytotoxicity to adrenal tissues as observed for many
      synthetic ACAT inhibitors. Beauveriolides I and III are the first microbial
      cyclodepsipeptides having an in vivo antiatherosclerotic effect and show promise
      as potential lead compounds for antiatherosclerotic agents.

PMID- 14718665
TI  - Closterovirus bipolar virion: evidence for initiation of assembly by minor coat
      protein and its restriction to the genomic RNA 5' region.
AB  - The long flexuous virions of the Closteroviridae have a unique bipolar
      architecture incorporating two coat proteins, with most of the helical
      nucleocapsid encapsidated by the major coat protein (CP) and a small portion of
      one end encapsidated by the minor coat protein (CPm). It is not known whether CPm
      encapsidates the genomic RNA and, if so, which end and what effects transition
      between the two coat proteins. Two other virus-encoded proteins, an HSP70 homolog
      (HSP70h) and an approximately 61-kDa protein, are required to augment virion
      assembly. In this work, we examine the in vivo encapsidation of Citrus tristeza
      virus by its CPm in the absence of CP. In the absence of other assembly-related
      proteins, CPm protected a family of 5' coterminal RNAs, apparently because of
      pausing at different locations along the genomic RNA. Most of the nucleocapsids
      formed by CPm were short, but a few were full-length and infectious. Mutations
      within the 5' nontranslated region demonstrated that the CPm origin of assembly
      overlaps the previously described conserved stem-and-loop structures that
      function as a cis-acting element required for RNA synthesis. Thus, in the absence
      of CP, the CPm encapsidation is initiated from the 5' end of the genomic RNA.
      Coexpression of HSP70h and the p61 protein with CPm in protoplasts restricted
      encapsidation to the 5' approximately 630 nucleotides, which is close to the
      normal boundary of the bipolar virion, whereas the presence of either HSP70h or
      the p61 protein alone did not limit encapsidation by CPm.

PMID- 14718666
TI  - Prominent roles of the NorR and Fur regulators in the Escherichia coli
      transcriptional response to reactive nitrogen species.
AB  - We examined the genomewide transcriptional responses of Escherichia coli treated
      with nitrosylated glutathione or the nitric oxide (NO)-generator acidified sodium
      nitrite (NaNO(2)) during aerobic growth. These assays showed that NorR, a homolog
      of NO-responsive transcription factors in Ralstonia eutrophus, and Fur, the
      global repressor of ferric ion uptake, are major regulators of the response to
      reactive nitrogen species. In contrast, SoxR and OxyR, regulators of the E. coli
      defenses against superoxide-generating compounds and hydrogen peroxide,
      respectively, have minor roles. Moreover, additional regulators of the E. coli
      response to reactive nitrogen species remain to be identified because several of
      the induced genes were regulated normally in norR, fur, soxRS, and oxyR mutant
      strains. We propose that the E. coli transcriptional response to reactive
      nitrogen species is a composite response mediated by the modification of multiple
      transcription factors containing iron or redox-active cysteines, some
      specifically designed to sense NO and its derivatives and others that are
      collaterally activated by the reactive nitrogen species.

PMID- 14718667
TI  - The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and
      progenitor cells in transgenic zebrafish and humans.
AB  - The solitary LTRs of ERV-9 human endogenous retrovirus are middle repetitive DNAs
      associated with 3,000-4,000 human gene loci including the beta-globin gene locus
      where the ERV-9 LTR is juxtaposed to the locus control region (beta-LCR) far
      upstream of the globin genes. The ERV-9 LTRs are conserved during primate
      evolution, but their function in the primate genomes is unknown. Here, we show
      that in transgenic zebrafish harboring the beta-globin ERV-9 LTR coupled to the
      GFP gene, the LTR enhancer was active and initiated synthesis of GFP mRNA in
      oocytes but not in spermatozoa, and GFP expression in the embryos was maternally
      inherited. The LTR enhancer was active also in stem/progenitor cell regions of
      adult tissues of transgenic zebrafish. In human tissues, ERV-9 LTR enhancer was
      active also in oocytes and stem/progenitor cells but not in spermatozoa and a
      number of differentiated, adult somatic cells. Transcriptional analyses of the
      human beta-globin gene locus showed that the beta-globin ERV-9 LTR enhancer
      initiated RNA synthesis from the LTR in the direction of the downstream beta
      locus control region and globin genes in ovary and erythroid progenitor cells.
      The findings suggest that, during oogenesis, ERV-9 LTR enhancers in the human
      genome could activate the cis-linked gene loci to synthesize maternal mRNAs
      required for early embryogenesis. Alternatively, the ERV-9 LTR enhancers, in
      initiating RNA syntheses into the downstream genomic DNAs, could
      transcriptionally potentiate and preset chromatin structure of the cis-linked
      gene loci in oocytes and adult stem/progenitor cells.

PMID- 14718668
TI  - Chemogenomic profiling: identifying the functional interactions of small
      molecules in yeast.
AB  - We demonstrate the efficacy of a genome-wide protocol in yeast that allows the
      identification of those gene products that functionally interact with small
      molecules and result in the inhibition of cellular proliferation. Here we present
      results from screening 10 diverse compounds in 80 genome-wide experiments against
      the complete collection of heterozygous yeast deletion strains. These compounds
      include anticancer and antifungal agents, statins, alverine citrate, and
      dyclonine. In several cases, we identified previously known interactions;
      furthermore, in each case, our analysis revealed novel cellular interactions,
      even when the relationship between a compound and its cellular target had been
      well established. In addition, we identified a chemical core structure shared
      among three therapeutically distinct compounds that inhibit the ERG24
      heterozygous deletion strain, demonstrating that cells may respond similarly to
      compounds of related structure. The ability to identify on-and-off target effects
      in vivo is fundamental to understanding the cellular response to small-molecule
      perturbants.

PMID- 14718669
TI  - Unexpected similarities in cellular responses to bacterial and viral invasion.

PMID- 14718670
TI  - Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins
      or selectins.
AB  - Expression of alphavbeta3- or alphavbeta5-integrins and selectins is widespread
      on blood cells and endothelial cells. Here we report that human tumor cells
      injected s.c. into mice lacking beta3- or beta3/beta5-integrins or various
      selectins show enhanced tumor growth compared with growth in control mice. There
      was increased angiogenesis in mice lacking beta3-integrins, but no difference in
      structure of the vessels was observed by histology or by staining for NG2 and
      smooth muscle actin in pericytes. Bone marrow transplants suggest that the
      absence of beta3-integrins on bone marrow-derived host cells contributes to the
      enhanced tumor growth in beta3-null mice, although few, if any, bone marrow
      derived endothelial cells were found in the tumor vasculature. Tumor growth also
      was affected by bone marrow-derived cells in mice lacking any one or all three
      selectins, implicating both leukocyte and endothelial selectins in tumor
      suppression. Reduced infiltration of macrophages was observed in tumors grown in
      mice lacking either beta3-integrins or selectins. These results implicate cells
      of the innate immune system, macrophages or perhaps natural killer cells, in each
      case dependent on integrins and selectins, in tumor suppression.

PMID- 14718671
TI  - Correct tonotopic representation is necessary for complex pitch perception.
AB  - The ability to extract a pitch from complex harmonic sounds, such as human
      speech, animal vocalizations, and musical instruments, is a fundamental attribute
      of hearing. Some theories of pitch rely on the frequency-to-place mapping, or
      tonotopy, in the inner ear (cochlea), but most current models are based solely on
      the relative timing of spikes in the auditory nerve. So far, it has proved to be
      difficult to distinguish between these two possible representations, primarily
      because temporal and place information usually covary in the cochlea. In this
      study, "transposed stimuli" were used to dissociate temporal from place
      information. By presenting the temporal information of low-frequency sinusoids to
      locations in the cochlea tuned to high frequencies, we found that human subjects
      displayed poor pitch perception for single tones. More importantly, none of the
      subjects was able to extract the fundamental frequency from multiple low
      frequency harmonics presented to high-frequency regions of the cochlea. The
      experiments demonstrate that tonotopic representation is crucial to complex pitch
      perception and provide a new tool in the search for the neural basis of pitch.

PMID- 14718672
TI  - Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse
      model of t(12;13)(p13;q12) acute myeloid leukemia.
AB  - Creation of fusion genes by balanced chromosomal translocations is one of the
      hallmarks of acute myeloid leukemia (AML) and is considered one of the key
      leukemogenic events in this disease. In t(12;13)(p13;q12) AML, ectopic expression
      of the homeobox gene CDX2 was detected in addition to expression of the ETV6-CDX2
      fusion gene, generated by the chromosomal translocation. Here we show in a murine
      model of t(12;13)(p13;q12) AML that myeloid leukemogenesis is induced by the
      ectopic expression of CDX2 and not by the ETV6-CDX2 chimeric gene. Mice
      transplanted with bone marrow cells retrovirally engineered to express Cdx2
      rapidly succumbed to fatal and transplantable AML. The transforming capacity of
      Cdx2 depended on an intact homeodomain and the N-terminal transactivation domain.
      Transplantation of bone marrow cells expressing ETV6-CDX2 failed to induce
      leukemia. Furthermore, coexpression of ETV6-CDX2 and Cdx2 in bone marrow cells
      did not accelerate the course of disease in transplanted mice compared to Cdx2
      alone. These data demonstrate that activation of a protooncogene by a balanced
      chromosomal translocation can be the pivotal leukemogenic event in AML,
      characterized by the expression of a leukemia-specific fusion gene. Furthermore,
      these findings link protooncogene activation to myeloid leukemogenesis, an
      oncogenic mechanism so far associated mainly with lymphoid leukemias and
      lymphomas.

PMID- 14718673
TI  - How risky is risk assessment: the role that life history strategies play in
      susceptibility of species to stress.
AB  - Measurements of toxicity based on individuals, such as the LC(50) (concentration
      that kills 50% of a population), and effects on reproduction are used extensively
      in determining ecological risk, in particular, for endangered or threatened
      species. An underlying assumption is that individual-based toxicity metrics for
      one species can be directly compared with that for another species. However, this
      assumption overlooks the fact that different species have different life-history
      strategies and variables, such as lifespan, time to first reproduction, and
      number of offspring produced over a lifetime. Using a simple model and laboratory
      derived parameter values, we tested the impact of differences in life-history
      traits on predicted responses to stress. The model predicts the delay in
      population growth. We compared seven invertebrate species by imposing 50% chronic
      mortality, 50% reduction of offspring, and both of these effects. The model
      predicted substantial differences in population delay among all of the species.
      Furthermore, the intrinsic rate of increase of each population was negatively
      correlated with the delay in population growth; species with high intrinsic rates
      of increase were less susceptible to equal levels of stress than species with
      lower intrinsic rates of increase. These results suggest that the susceptibility
      of species to pollutants is more complicated than previously thought and that
      differences in life-history variables must be considered in analyses of
      population persistence for threatened and endangered species.

PMID- 14718675
TI  - Unmet medical needs in Parkinson's disease.
AB  - Levodopa, introduced in the late 1960s, was the first highly effective drug for
      the symptomatic treatment of Parkinson's disease (PD) and remains the mainstay of
      pharmacologic treatment. However, long-term treatment has important limitations.
      The disease continues to progress despite treatment with levodopa, and a
      neuroprotective therapy is urgently required. In addition, motor complications
      associated with chronic levodopa therapy are an important source of disability.
      Treatment of these complications forms a major focus of modern PD management, and
      it is in this area that recent advances in our knowledge offer the best
      opportunity for therapeutic gain. In the search for improved therapies, suitable
      outcome measures to better assess overall disability in PD and disease
      progression are essential.

PMID- 14718674
TI  - Increased and altered fragrance of tobacco plants after metabolic engineering
      using three monoterpene synthases from lemon.
AB  - Wild-type tobacco (Nicotiana tabacum) plants emit low levels of terpenoids,
      particularly from the flowers. By genetic modification of tobacco cv Petit Havana
      SR1 using three different monoterpene synthases from lemon (Citrus limon L. Burm.
      f.) and the subsequent combination of these three into one plant by crossings, we
      show that it is possible to increase the amount and alter the composition of the
      blend of monoterpenoids produced in tobacco plants. The transgenic tobacco plant
      line with the three introduced monoterpene synthases is emitting beta-pinene,
      limonene, and gamma-terpinene and a number of side products of the introduced
      monoterpene synthases, from its leaves and flowers, in addition to the terpenoids
      emitted by wild-type plants. The results show that there is a sufficiently high
      level of substrate accessible for the introduced enzymes.

PMID- 14718676
TI  - New developments in levodopa therapy.
AB  - More than 30 years after its development, levodopa is still the most effective
      treatment for the symptomatic control of Parkinson's disease (PD). Although a
      number of therapies have been developed in an attempt to improve PD management,
      such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients
      still depend on levodopa alone because of its superior ability to control PD
      symptoms. The issue of toxicity has been raised by in vitro studies suggesting
      that levodopa might be toxic to dopaminergic neurons, but this has since been
      answered by in vivo studies finding no evidence of toxicity and possibly even
      neurotrophic-like effects. A more pressing concern regarding levodopa is its
      association with the development of motor complications after long-term use.
      Pulsatile dopaminergic stimulation as a result of erratic absorption and the
      short half-life of levodopa have been central issues in attempts to explain this
      occurrence. Evidence suggests that altering the delivery of levodopa to provide a
      more continuous supply of this drug to the brain may result in improved control
      of PD symptoms.

PMID- 14718677
TI  - The origin of motor fluctuations in Parkinson's disease: importance of
      dopaminergic innervation and basal ganglia circuits.
AB  - The severity of dopamine depletion and the consequent pathophysiologic changes
      that occur in basal ganglia circuits determine the severity of parkinsonian
      signs. Restoring the dopamine deficit or the downstream physiologic abnormalities
      improves Parkinson's Disease (PD) main motor features and as a result, attenuates
      the short-duration response (SDR). Therefore, both the magnitude and duration of
      the motor response are a function of the degree of motor severity, which is
      primarily governed by the loss of tonic dopaminergic activity and disruption of
      basal ganglia homeostatic mechanisms among which the STN-GPe/GPi circuits play a
      fundamental role. As neurodegeneration advances, standard levodopa administration
      give rises to wider oscillations in striatal dopamine availability and
      "pulsatile" stimulation of striatal dopamine receptors becomes predominant. This
      induces molecular and physiologic changes that further accentuate and aggravate
      the SDR that sustains motor fluctuations. Treatments capable of providing and
      restoring more tonic and physiologic dopaminergic stimulation may avoid many of
      these abnormalities and lead to better clinical outcomes.

PMID- 14718678
TI  - The role of COMT inhibition in the treatment of Parkinson's disease.
AB  - Several prospective double-blind, placebo-controlled trials have demonstrated
      that combining levodopa with the COMT inhibitor entacapone is efficacious in
      reducing motor fluctuations. Compared with levodopa alone, mean daily "on" time
      was increased by 1-1.7 hours, with a corresponding decrease in daily "off" time.
      In addition, some studies have shown that these benefits are associated with
      significant improvements in both UPDRS motor and ADL scores. These benefits have
      been shown to persist in long-term clinical trials with follow-up for up to 3
      years. Recent studies have also examined the value of combining levodopa with
      entacapone in stable patients who do not experience motor response fluctuations.
      Here, too, benefits have been reported, especially in health-related quality of
      life measures. Studies to determine if administering levodopa in combination with
      entacapone will delay the development of dyskinesia and motor fluctuations are
      eagerly awaited.

PMID- 14718679
TI  - Safety and tolerability of COMT inhibitors.
AB  - Combining levodopa with the catechol-O-methyltransferase (COMT) inhibitor
      entacapone has been shown to be an effective strategy in the management of
      Parkinson's disease (PD) patients experiencing motor fluctuations. Safety and
      tolerability information has come from postmarketing surveillance studies as well
      as several randomized, placebo-controlled trials with long-term open-label
      extension phases specifically investigating the safety and tolerability of
      levodopa plus entacapone. Results show the most common dopaminergic side effects
      to be dyskinesia and nausea, which result from the increased bioavailability of
      levodopa and can be readily managed. Non-dopaminergic side effects include
      diarrhea and harmless urine discoloration. There is no convincing evidence of
      hepatic injury with entacapone use, and therefore monitoring of liver enzymes is
      unnecessary. With over 300,000 patient-years of exposure, levodopa combined with
      entacapone can be considered safe and well tolerated.

PMID- 14718680
TI  - Avoidance of dyskinesia: preclinical evidence for continuous dopaminergic
      stimulation.
AB  - Current concepts suggest that avoidance of pulsatile stimulation of dopamine
      receptors in Parkinson's disease (PD) can prevent the onset of dyskinesia. In
      MPTP-treated primates, repeated administration of levodopa or other short-acting
      dopamine agonist drugs leads to the onset of marked involuntary movements. In
      contrast, treatment with long-acting dopamine agonists leads to a much lower
      level of dyskinesia. Similar results have been obtained in PD patients, although
      the introduction of levodopa is a requirement in virtually all patients and this
      leads to further increases in motor complications. The concept of continuous
      dopaminergic stimulation should also apply to levodopa, such that reduced
      dyskinesia would be expected if it could be administered in a manner that avoids
      pulsatile receptor stimulation. In MPTP monkeys, administration of multiple small
      doses of levodopa in conjunction with the peripheral COMT inhibitor entacapone
      removes much of the pulsatility of motor function seen with standard levodopa
      treatment regimens and, at the same time, results in a lower incidence and
      intensity of dyskinesia. Furthermore, the addition of multiple small doses of
      levodopa plus entacapone to dopamine agonist treatment also avoids dyskinesia
      induction in MPTP-treated primates. These results suggest that administering of
      levodopa with entacapone as either initial or supplemental therapy for PD
      patients might reduce the risk for motor complications. Clinical trials to assess
      this hypothesis and determine if the results in MPTP monkeys can be duplicated in
      PD patients are warranted.

PMID- 14718681
TI  - Continuous dopaminergic stimulation in early and advanced Parkinson's disease.
AB  - Evidence from preclinical and clinical studies indicates that pulsatile
      stimulation of striatal dopamine receptors is a key factor in the development of
      levodopa-associated motor complications. Therefore, in the de novo patient it is
      believed that providing a more continuous dopaminergic stimulation from the start
      of antiparkinson therapy may prevent priming for motor fluctuations and
      dyskinesia. Conversely, in the more advanced patient who is already suffering
      from motor complications, it is believed that providing a more continuous
      stimulation may reverse the development of motor complications, enabling the
      patient to enjoy more stable benefits from therapy. All PD patients eventually
      require levodopa therapy during the course of their disease, and the benefits of
      providing continuous dopaminergic stimulation with levodopa have been clearly
      demonstrated in a number of studies. However, these studies have included the use
      of approaches such as SC infusion or intra-intestinal infusion. Because these are
      relatively difficult to handle and not very practical for the patient, compliance
      is generally low. Therefore, the development of a simple treatment regimen using
      an oral formulation of levodopa to provide a more continuous dopaminergic
      stimulation will represent a significant advance in antiparkinsonian
      pharmacotherapy.

PMID- 14718682
TI  - Levodopa/carbidopa/entacapone (Stalevo).
AB  - A levodopa/carbidopa/entacapone combination product (Stalevo) was recently
      approved to treat patients with idiopathic Parkinson's disease (PD) who
      experience end-of-dose "wearing-off." Stalevo is available in dose combinations
      of levodopa/carbidopa/entacapone 50/12.5/200 mg (Stalevo 50), 100/25/200 mg
      (Stalevo 100), and 150/37.5/200 mg (Stalevo 150). A series of pharmacokinetic
      studies demonstrated bioequivalence between Stalevo and corresponding dosages of
      levodopa/carbidopa plus entacapone. A clinical advantage of Stalevo is that
      patients can take one pill rather than two (or more) separate tablets. In
      addition, Stalevo 50 and 100 tablets are smaller than entacapone tablets. These
      advantages may be particularly beneficial for patients taking many pills, those
      who have difficulty following complex medication regimens, and those with
      swallowing difficulty. Most PD patients taking levodopa/carbidopa immediate
      release (IR) plus entacapone can be directly switched to the corresponding dose
      Stalevo product. For fluctuating PD patients taking levodopa/carbidopa IR without
      entacapone, switching to the corresponding Stalevo tablet is analogous to adding
      entacapone. In switching patients who are receiving levodopa/carbidopa controlled
      release (CR), it should be noted that the bioavailability of levodopa from
      levodopa/carbidopa CR is approximately 70-75% that of levodopa/carbidopa IR
      products, including Stalevo.

PMID- 14718683
TI  - COMT inhibitors in Parkinson's disease: can they prevent and/or reverse levodopa
      induced motor complications?
AB  - COMT inhibitors have historically been used as adjuncts to levodopa in
      fluctuating PD patients to increase "on" time and reduce "off" time. Evidence
      that motor complications are related to intermittent or pulsatile stimulation of
      striatal dopamine receptors has led to the use of long-acting dopaminergic
      therapies that provide more continuous dopaminergic stimulation (CDS). CDS-based
      therapies are associated with the prevention and reversal of levodopa-related
      motor complications in MPTP-lesioned primates and PD patients. However, levodopa
      remains the most effective and widely used anti-parkinsonian agent and is
      eventually required in all PD patients. The standard oral formulation of levodopa
      has a relatively short half-life and is associated with the development of motor
      complications when used as either initial or supplemental therapy. The CDS
      concept raises the possibility that administration of levodopa in combination
      with a COMT inhibitor to extend its half-life might reduce the risk of inducing
      motor complications. This article considers the possibility that combining
      levodopa with entacapone may prevent or reverse motor complications.

PMID- 14718684
TI  - Neurology 2004.

PMID- 14718685
TI  - Want to improve epilepsy care?: Ask the patient.

PMID- 14718686
TI  - Neurobehavioral teratogenicity in antiepileptic drugs: the new Pandora's box.

PMID- 14718687
TI  - ARSACS goes global.

PMID- 14718688
TI  - Introducing the resident and fellow page.

PMID- 14718689
TI  - Clinical and molecular findings in patients with giant axonal neuropathy (GAN).
AB  - Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative
      disorder of early onset, clinically characterized by a progressive involvement of
      both peripheral and CNS. The diagnosis is based on the presence of characteristic
      giant axons, filled with neurofilaments, on nerve biopsy. Recently, the defective
      protein, gigaxonin, has been identified and different pathogenic mutations in the
      gigaxonin gene have been reported as the underlying genetic defect. Gigaxonin, a
      member of the BTB/kelch superfamily proteins, seems to play a crucial role in the
      cross talk between the intermediate filaments and the membrane network. The
      authors report clinical and molecular findings in five Italian patients with GAN.
      This study shows the allelic heterogeneity of GAN and expands the spectrum of
      mutations in the GAN gene. The frequent occurrence of private mutations stresses
      the importance of a complete gene analysis.

PMID- 14718690
TI  - Clinical spectrum of episodic ataxia type 2.
AB  - The authors searched for mutations in CACNA1A in patients with episodic ataxia
      and describe the clinical spectrum in genetically defined patients. Eighteen
      families and nine sporadic cases of episodic ataxia were evaluated for mutations
      in CACNA1A. The families were first genotyped to check for linkage to the
      chromosome 19p locus of CACNA1A. In families consistent with linkage and in the
      sporadic cases, the authors screened for polymorphisms in CACNA1A using single
      strand conformational polymorphism and denaturing high performance liquid
      chromatography followed by direct sequencing to identify specific nucleotide
      changes. Of the 18 families, 11 were linked to 19p and mutations were found in 9.
      Mutations were detected in four of the nine sporadic cases. Overall, five
      nonsense mutations, four missense mutations, two deletions, one insertion, and
      one donor splice mutation were identified. All but two of the 64 genetically
      defined patients reported episodes of ataxia (two members of one family only had
      progressive ataxia). All but one had onset before age 20 and all but four had
      interictal nystagmus. Migraine headaches occurred in more than half, and about
      two thirds reported a good response to treatment with acetazolamide. Vertigo and
      weakness accompanied the ataxia in more than half of the genetically defined
      patients. One family had multiple members with epilepsy. A wide range of
      mutations in CACNA1A were associated with episodic ataxia. Four of 13 were
      missense mutations; the remainder predicted truncated proteins. The mutations
      were scattered throughout the gene, and only 2 of the 13 mutations identified in
      our laboratory have been reported by other laboratories, so it will not be
      possible to screen a few "hot spots" in CACNA1A. Overall, the type of mutation,
      missense versus nonsense, or the location of altered or truncated amino acid
      residues did not predict the clinical phenotype.

PMID- 14718691
TI  - Systematic screening allows reduction of adverse antiepileptic drug effects: a
      randomized trial.
AB  - OBJECTIVE: To determine the effectiveness of systematic screening with a brief 19
      item self-report instrument, the Adverse Events Profile (AEP), to reduce adverse
      effects of antiepileptic drugs (AEDs) and improve subjective health status.
      METHODS: The authors performed a prospective randomized trial comparing the use
      of the AEP with usual care without the AEP. Sixty-two patients with an AEP score
      of >or=45 were enrolled from a consecutive group of 200 consenting adults with
      epilepsy. RESULTS: The mean percent improvement in AEP scores was greater in the
      patient group for which clinicians received the AEP compared with the usual care
      group (25% vs 5%; p < 0.01). Mean change in Quality of Life in Epilepsy Inventory
      (QOLIE)-89 total scores was not different between groups, but for the entire
      sample QOLIE-89 change was greater for patients having a 15-point improvement in
      AEP scores than for those with a 0- to 15-point improvement or a worsened score
      (24 vs 12 vs 3; analysis of variance, p < 0.008). More patients in the AEP group
      had a >15-point improvement in QOLIE-89 score (p < 0.03). Use of the AEP was
      associated with a 2.8-fold increase (95% CI, 1.7 to 4.8) in AED modifications. No
      difference in seizure rates was observed. CONCLUSIONS: Systematic screening for
      antiepileptic drug side effects may increase identification of toxicity and guide
      medication changes to reduce adverse effects and possibly improve subjective
      health status.

PMID- 14718692
TI  - Normal intelligence in children with prenatal exposure to carbamazepine.
AB  - OBJECTIVE: To investigate the effect of antiepileptic drugs, especially
      carbamazepine and valproate, on intelligence in prenatally exposed children of
      mothers with epilepsy. METHODS: Intelligence of 182 children of mothers with
      epilepsy (study group) and 141 control children was tested in a blinded setting
      at preschool or school age using Wechsler Preschool and Primary Scale of
      Intelligence-Revised or Wechsler Intelligence Scale for Children-Revised. Data on
      maternal antiepileptic treatment and seizures during pregnancy were gathered
      prospectively. The study group represented approximately 50% of the children born
      to mothers with epilepsy in Uusimaa province during 1989 through 1994. One
      hundred seven children were exposed to antiepileptic monotherapy: 86 to
      carbamazepine and 13 to valproate. Thirty children were exposed to polytherapy:
      23 combinations included carbamazepine, and 17 included valproate. The median
      maternal doses and blood levels during the second half of pregnancy were 600 mg
      and 26 micro mol/L for carbamazepine and 950 mg and 300 micro mol/L for
      valproate. RESULTS: The mean verbal and nonverbal IQ scores in the children
      exposed in utero to carbamazepine monotherapy were 96 (95% CI, 93-100) and 103
      (95% CI, 100-106). They did not differ from control subjects, whose mean verbal
      and nonverbal IQ scores were 95 (95% CI, 92-97) and 102 (95% CI, CI, 100-105).
      Significantly reduced verbal IQ scores were found in children exposed to
      valproate (mean, 82; 95% CI, 78-87) and to polytherapy (mean, 85; 95% CI, 80-90)
      compared with the other study group children and control subjects. CONCLUSIONS:
      Carbamazepine monotherapy with maternal serum levels within the reference range
      does not impair intelligence in prenatally exposed offspring. Exposures to
      polytherapy and to valproate during pregnancy were associated with significantly
      reduced verbal intelligence. The independent effects of valproate remain
      unconfirmed because the results were confounded by low maternal education and
      polytherapy.

PMID- 14718693
TI  - Abducens length and vulnerability?
AB  - BACKGROUND: Several sources have attributed the vulnerability of the abducens
      nerve to its long intracranial course. However, other anatomic factors likely
      contribute to the apparent vulnerability of the abducens nerve to mass lesions
      and trauma. METHODS: The authors performed a two-part anatomic study of the
      abducens nerve. In the first part of the study, they compared the length of the
      abducens with another cranial nerve, the trochlear, at the autopsy of 26
      pediatric patients. In the second part of the study, the authors used an
      endoscopic exposure of these two cranial nerves in a preserved human cadaver
      head. RESULTS: The abducens nerve was consistently approximately one-third the
      length of the trochlear nerve at all ages that they studied. The endoscopic views
      revealed the structural and vascular relationships of the abducens nerve in situ.
      CONCLUSIONS: The authors conclude from these findings and the literature that
      abducens nerve vulnerability results from factors other than its intracranial
      length.

PMID- 14718694
TI  - A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in
      Parkinson's disease.
AB  - BACKGROUND: Injections of botulinum toxin A are an effective treatment for
      sialorrhea in Parkinson's disease (PD). Based on the relatively high rates of dry
      mouth seen with botulinum toxin B, there is reason to suspect that it may also
      improve sialorrhea. OBJECTIVE: To determine whether botulinum toxin B (Myobloc;
      Elan Pharmaceuticals, New York, NY) is a safe and effective treatment for
      sialorrhea in patients with PD. METHODS: Demographics, PD treatments, head
      posture, the Unified Parkinson's Disease Rating Scale (UPDRS), two questionnaires
      regarding drooling, Visual Analogue Scale, global impressions, salivary gland
      imaging, and a dysphagia questionnaire were assessed in 16 PD subjects with
      problematic sialorrhea. Patients were then randomized to receive either botulinum
      toxin B (1,000 units into each parotid gland and 250 units into each
      submandibular gland) or a pH-matched placebo, using only anatomic landmarks.
      Patients returned 1 month later to undergo an identical assessment. RESULTS:
      Compared with placebo, those randomized to drug reported improvement on the
      Visual Analogue Scale (p < 0.001), global impressions of change (p < 0.005),
      Drooling Rating Scale (p < 0.05), and Drooling Severity and Frequency Scale (p <
      0.001). There was no change in UPDRS, head posture, or Dysphagia Scale. Adverse
      events were mild and included dry mouth (three patients), worsened gait (two),
      diarrhea (one), and neck pain (one) in the botulinum toxin B group. CONCLUSION:
      Anatomically guided injections of botulinum toxin B into the parotid and
      submandibular glands appear to effectively improve sialorrhea without
      compromising dysphagia in patients with PD.

PMID- 14718695
TI  - Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD):
      does the idiopathic form of RBD really exist?
AB  - OBJECTIVE: To evaluate the cognitive performance of patients with idiopathic REM
      sleep behavior disorder (RBD). METHODS: The authors studied 17 consecutive
      patients with idiopathic RBD vs 17 age- and education-matched control subjects.
      Tests given to each patient and control included Mini-Mental State Examination,
      verbal and spatial short-term memory, visual selective attention, verbal fluency,
      prose memory, visuoconstructional abilities, spatial learning, and executive
      function tests. A self-administered depression rating scale was also used.
      RESULTS: RBD patients had significantly lower scores than control subjects in two
      tests: copy of Rey-Osterrieth Figure and Corsi Supraspan Learning. No correlation
      was found between the results of neuropsychological tests and RBD duration or
      with polysomnographic findings. CONCLUSIONS: Visuospatial constructional
      dysfunction and altered visuospatial learning may be present in idiopathic RBD. A
      neuropsychological assessment may be indicated in RBD patients.

PMID- 14718696
TI  - Effect of age on MSLT results in patients with narcolepsy-cataplexy.
AB  - OBJECTIVE: To measure the effect of age on Multiple Sleep Latency Test
      (MSLT)characteristics, sleep latency, and number of sleep-onset REM periods
      (SOREMP) in two large populations of narcoleptic patients with similar genetic
      backgrounds. METHODS: Clinical and polygraphic information on the severity of the
      condition was obtained on 236 well-defined narcolepsy-cataplexy-human leukocyte
      antigen DR2-positive patients from Montpellier (France) and on 147 similar
      patients from Montreal (Canada). RESULTS: The results show a progressive decrease
      in the number of SOREMP with age and a progressive increase in the mean sleep
      latency on the MSLT as a function of age. This finding is also related to the
      severity of cataplexy as assessed from the clinical history with a progressive
      decrease in the frequency of cataplexy attacks with age. These results may
      reflect the progressive increase in sleep latency seen in normal aging and
      suggest that clinical improvement might be due to changes in the neural
      mechanisms responsible for SOREMP, which may weaken with age. CONCLUSIONS: The
      progressive decrease in the number of SOREMP and increase in the mean sleep
      latency on the MSLT as a function of age suggest that the current criteria used
      for diagnosis may be too stringent in older patients. The major influence of age
      on MSLT results should therefore be taken into account when diagnosing a
      narcoleptic patient.

PMID- 14718697
TI  - Change in MS-related disability in a population-based cohort: a 10-year follow-up
      study.
AB  - OBJECTIVE: S: To study the change in disability over 10 years in individual
      patients constituting the 1991 Olmsted County, MN, multiple sclerosis (MS)
      prevalence cohort. METHODS: The authors reassessed this 1991 cohort in 2001. The
      authors determined the Expanded Disability Status Scale scores (EDSS) for each
      patient still alive, and within the year prior to death for those who died. The
      authors analyzed determinants of potential prognostic significance on change in
      disability. RESULTS: Follow-up information was available for 161 of 162 patients
      in the 1991 cohort. Only 15% had received immunomodulatory therapy. The mean
      change in EDSS for the entire cohort over 10 years was 1 point and 20% worsened
      by >or=2 points. For patients with EDSS <3 in 1991 (n = 66), 83% were ambulatory
      without a cane 10 years later. For patients with EDSS of 3 through 5 in 1991 (n =
      33), 51% required a cane to ambulate (48%) or worse (3%). For patients with EDSS
      6 to 7 in 1991 (n = 39), 51% required a wheelchair or worse in 2001. Gait
      impairment at onset, progressive disease, or longer duration of disease were
      associated with more worsening of disability (p < 0.002). The 10-year survival
      was decreased compared with the Minnesota white population for both men and
      women. CONCLUSIONS: Although survival was reduced and 30% of patients progressed
      to needing a cane or wheelchair or worse over the 10-year follow-up period, most
      remained stable or minimally progressed. Patients within the EDSS 3.0 through 5.0
      range are at moderate risk of developing important gait limitations over the 10
      year period. The authors did not identify factors strongly predictive of
      worsening disability in this study.

PMID- 14718698
TI  - Vitamin D intake and incidence of multiple sclerosis.
AB  - BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS)
      has been proposed, but no prospective studies have addressed this hypothesis.
      METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS
      in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women
      followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women
      followed from 1991 to 2001). Diet was assessed at baseline and updated every 4
      years thereafter. During the follow-up, 173 cases of MS with onset of symptoms
      after baseline were confirmed. RESULTS: The pooled age-adjusted relative risk
      (RR) comparing women in the highest quintile of total vitamin D intake at
      baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend =
      0.03). Intake of vitamin D from supplements was also inversely associated with
      risk of MS; the RR comparing women with intake of >or=400 IU/day with women with
      no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend =
      0.006). No association was found between vitamin D from food and MS incidence.
      CONCLUSION: These results support a protective effect of vitamin D intake on risk
      of developing MS.

PMID- 14718699
TI  - Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded,
      controlled study.
AB  - BACKGROUND: Inflammatory mechanisms have been implicated in the pathogenesis of
      Alzheimer's disease (AD) and may be mediated via the cyclo-oxygenase-2 enzyme.
      This study sought to evaluate the effect of rofecoxib, a nonsteroidal anti
      inflammatory drug that selectively inhibits cyclo-oxygenase-2, in slowing the
      progression of dementia in patients with established AD. METHODS: A double
      blinded, multicenter trial was conducted in which 692 patients with mild or
      moderate AD aged 50 years or older were randomly assigned to receive 25 mg
      rofecoxib or placebo daily for 12 months. The key efficacy measures were mean
      change from baseline at month 12 on the cognitive subscale of the AD Assessment
      Scale (ADAS-cog) and score on the Clinician's Interview Based Impression of
      Change with caregiver input (CIBIC+). RESULTS: Four hundred eighty-one patients
      (70%) completed assessments and remained on treatment at 12 months. No
      significant differences between treatments were found on the mean change from
      baseline error score for the ADAS-cog (rofecoxib = 4.84; placebo = 5.44;
      difference = -0.60) or mean score on the CIBIC+ (rofecoxib = 4.90; placebo =
      4.87; difference = 0.03) over 12 months. This result persisted after adjusting
      for severity of dementia at baseline, presence of the APOE-epsilon4 allele, and
      donepezil use. Secondary analyses did not reveal any significant differences on
      any other measures. CONCLUSION: The failure of selective cyclo-oxygenase-2
      inhibition to slow the progression of AD may indicate either that the disease
      process is too advanced to modify in patients with established dementia or that
      cyclo-oxygenase-2 does not play a significant role in the pathogenesis of the
      disorder.

PMID- 14718700
TI  - Cerebral microbleeds are regionally associated with intracerebral hemorrhage.
AB  - BACKGROUND: Cerebral microbleeds (CMB) may be indicative of a hemorrhage-prone
      microangiopathy. OBJECTIVE: To determine if increased numbers of these lesions
      are predictive of intracerebral hemorrhage (ICH), especially in terms of a
      distributional association. METHODS: The authors examined consecutively 227
      patients with acute stroke. CMB were counted using T2*-weighted gradient echo MRI
      data, and old lacunes and leukoaraiosis were also evaluated. The associations
      between the vascular risk factors and ICH were analyzed. With use of multivariate
      logistic regression analysis, the locations of the CMB or the old lacunes, which
      were categorized as being in the corticosubcortical area, the deep gray matter
      area, or the infratentorial area, were examined with regard to their
      relationships to the locations of the ICH. RESULTS: The degrees of the CMB (r =
      0.43, p < 0.01) and leukoaraiosis (r = 0.20, p < 0.01) were well correlated with
      the presence of ICH. Multivariate analysis revealed that the grades of the CMB
      were associated with the presence of ICH (p < 0.01, odds ratio [OR] = 2.67). CMB
      in the corticosubcortical area (p < 0.01, OR = 5.50) or deep gray matter (p <
      0.01, OR = 2.55) were strongly associated with the presence of ICH in the same
      area, but no such association was observed in the case of CMB in the
      infratentorial area or in the case of old lacunes in any area. CONCLUSIONS:
      Cerebral microbleeds are strongly associated with the presence of intracerebral
      hemorrhage, and the distributional associations are also quite strong.

PMID- 14718701
TI  - Burden of first-ever ischemic stroke in the oldest old: evidence from a
      population-based study.
AB  - OBJECTIVE: To evaluate the contribution of subjects 80 years old or older to the
      burden of ischemic stroke as compared with subjects younger than 80 years.
      METHODS: All first-ever ischemic strokes occurring in a 5-year period (1994 to
      1998) in the population-based L'Aquila registry were traced. Incidence, total
      health care utilization, disability, and mortality were assessed in patients 80
      years old or older, and differences with those younger than 80 years were
      assessed by univariate and survival analyses. RESULTS: One thousand three hundred
      sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80
      years old or older, accounting on average for one-third of health care
      utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to
      22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability,
      20.7% had severe disability, and 51.6% had died. With respect to patients under
      80 years of age, older patients showed a higher proportion of women (61.3 vs
      47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs
      23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of
      cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%).
      Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in
      patients 80 years old or older than in those younger than 80, mostly in the
      presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality
      and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day
      mortality and 1.31 for 1-year mortality). CONCLUSION: The burden of ischemic
      stroke is high in subjects 80 years old or older, contributing about one-third of
      health care utilization and 59.8% of deaths within 30 days.

PMID- 14718702
TI  - No spontaneous second wind in muscle phosphofructokinase deficiency.
AB  - OBJECTIVE: The spontaneous second wind in myophosphorylase deficiency (MD,
      McArdle's disease) represents a transition from low to a higher exercise capacity
      attributable to increased oxidation of blood-borne fuels, principally glucose and
      free fatty acids. Muscle phosphofructokinase deficiency (PFKD) blocks the
      metabolism of muscle glycogen and blood glucose. The authors inquired whether the
      additional restriction in glucose metabolism in PFKD prevents a spontaneous
      second wind. METHODS: The authors compared the ability of 29 patients with MD and
      5 patients with muscle PFKD to achieve a spontaneous second wind during
      continuous cycle exercise after an overnight fast. Patients cycled at a constant
      workload for 15 to 20 minutes (3 MD patients, 3 PFKD patients) and at variable
      workloads in which peak exercise capacity was determined at 6 to 8 minutes of
      exercise and again at 25 to 30 minutes of exercise (29 MD patients, 4 PFKD
      patients). Heart rate was monitored continuously, and perceived exertion (Borg
      scale) was recorded during each minute of exercise. Oxygen utilization and blood
      levels of lactate and ammonia were determined at rest and during peak workloads.
      RESULTS: All variables in both patient groups were similar at 6 to 8 minutes of
      exercise. Thereafter exercise responses diverged. Each MD patient developed a
      second wind with a decrease in heart rate and perceived exertion and an increase
      in work and oxidative capacity. In contrast, no PFKD patient developed a
      spontaneous second wind. CONCLUSIONS: Patients with muscle phosphofructokinase
      deficiency are unable to achieve a spontaneous second wind under conditions that
      consistently produce one in patients with McArdle's disease. The authors conclude
      that the ability to metabolize blood glucose is critical to the development of a
      typical spontaneous second wind.

PMID- 14718703
TI  - Infantile bilateral striatal necrosis maps to chromosome 19q.
AB  - BACKGROUND: Infantile bilateral striatal necrosis (IBSN) encompasses several
      syndromes of bilateral symmetric degeneration of the caudate nucleus, putamen,
      and globus pallidus. Autosomal recessive IBSN is characterized clinically by
      developmental arrest beginning at age 7 to 15 months, dysphagia, choreoathetosis,
      pendular nystagmus and optic atrophy, and severe progressive atrophy of the basal
      ganglia on MRI. OBJECTIVE: To map the gene causing IBSN. METHODS: A 10-cM genome
      wide linkage scan was initially performed on five affected and five unaffected
      individuals. The extended family was included in the analysis to narrow the
      candidate region. Logarithm of odds (LOD) score was calculated using the
      SUPERLINK program. RESULTS: Linkage to the chromosomal region 19q13.32-13.41 was
      established (Z(max) = 6.27 at theta = 0.02 at locus D19S412). Recombination
      events and a common disease-bearing haplotype defined a critical region of 1.2 Mb
      between the loci D19S596 proximally and D19S867 distally. CONCLUSION: IBSN maps
      to the chromosomal region 19q13.32-13.41. The presence of a common haplotype in
      all the patients suggests that the disease is caused by a single mutation derived
      from a single ancestral founder in all the families.

PMID- 14718704
TI  - Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger
      movements.
AB  - BACKGROUND: Disruption of cortical function can improve behavior. Motor cortex
      (M1) transcallosal interactions are mainly inhibitory; after unilateral damage to
      M1, there is increased excitability of the unaffected M1. Repetitive transcranial
      magnetic stimulation (rTMS) of M1 produces a temporary reduction in cortical
      excitability in the same M1 that outlasts the duration of the rTMS train. The
      authors hypothesize that reducing cortical excitability of M1 by rTMS may improve
      motor performance in the ipsilateral hand by releasing the contralateral M1 from
      transcallosal inhibition. METHODS: Sixteen healthy volunteers participated. Using
      a sequential key-pressing task with the index finger, motor performance was
      monitored before and after rTMS (1 Hz for 10 minutes with the intensity below
      motor threshold) applied to the ipsilateral M1, contralateral M1, ipsilateral
      premotor area, or vertex (Cz). RESULTS: rTMS of M1 shortened execution time of
      the motor task with the ipsilateral hand without affecting performance with the
      contralateral hand. This effect outlasted rTMS by at least 10 minutes, was
      specific for M1 stimulation, and was associated with increased intracortical
      excitability in the unstimulated M1. CONCLUSIONS: The authors' results support
      the concept of an interhemispheric "rivalry." They demonstrate the utility of
      repetitive transcranial magnetic stimulation to explore the functional
      facilitation of the unstimulated counterpart motor cortex, presumably via
      suppression of activity in the stimulated motor cortex and transcallosal
      inhibition.

PMID- 14718705
TI  - Wyburn-Mason syndrome.

PMID- 14718706
TI  - A novel mutation in SACS gene in a family from southern Italy.
AB  - A form of autosomal recessive spastic ataxia (ARSACS) has been described in the
      Charlevoix and Saguenay regions of Quebec. So far a frameshift and a nonsense
      mutation have been identified in the SACS gene. The authors report a new mutation
      (1859insC), leading to a frameshift with a premature termination of the gene
      product sacsin, in two sisters from consanguineous parents. The phenotype is
      similar to previously described patients with ARSACS.

PMID- 14718707
TI  - Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay
      type.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early
      onset familial disease with prominent myelinated fibers in the optic fundus.
      ARSACS is frequent in the Charlevoix-Saguenay region of Quebec but rare
      elsewhere. Mutations in SACS, encoding sacsin, a protein of unknown function, are
      associated with ARSACS. The authors identified three new SACS mutations in two
      Italian patients whose phenotype closely matches that of Quebec cases, but
      without retinal striation.

PMID- 14718708
TI  - Identification of a SACS gene missense mutation in ARSACS.
AB  - The authors describe two patients in a Japanese family with autosomal recessive
      spastic ataxia of Charlevoix-Saguenay. They presented early onset spastic ataxia,
      sensorimotor neuropathy, nystagmus, slurred speech, and hypermyelinated retinal
      nerve fibers. The authors identified a homozygous missense mutation (T7492C) in
      the SACS gene, which resulted in the substitution of arginine for tryptophan at
      amino acid residue 2498 (W2498R).

PMID- 14718709
TI  - Delusional state following acute stroke.
AB  - Delusional ideations (DIs) were seen in 15 patients in a prospective cohort
      population (n = 360) with acute stroke admitted within 24 hours of onset.
      Specific DIs may occur during the acute stroke phase, but atypical forms with
      distinct behavioral findings have also been observed. DIs are associated with
      right posterior temporoparietal lesions. However, distinct lesions were also
      seen, and duration was relatively short, mostly less than 1 month.

PMID- 14718710
TI  - The acoustic startle reflex in ischemic stroke.
AB  - The authors recorded the acoustic startle response in 32 patients with stroke, 6
      patients with incomplete cervical cord lesions, and 26 controls. Increased
      startle occurred in about one quarter of both stroke and spinal cord injury
      patients. The response in biceps demonstrated the greatest deviation from normal,
      with less marked changes in tibialis anterior. Increased startle in spinal cord
      injury suggests that changes at the segmental level may contribute. Symptomatic
      increased startle occurred only in pontine lesions.

PMID- 14718711
TI  - A case of frequently recurring amaurosis fugax with atherothrombotic ophthalmic
      artery occlusion.
AB  - A 49-year-old woman with diabetes mellitus and hyperlipidemia experienced
      frequent transient monocular blindness in the right eye during a 3-week period.
      Examination revealed atherothrombotic occlusion of the right ophthalmic artery
      (OA) without embolic sources. After treatment with aspirin, attacks resolved
      completely. Her symptoms were attributed to microembolism from the occluded OA.

PMID- 14718712
TI  - Do malpractice concerns, payment mechanisms, and attitudes influence test
      ordering decisions?
AB  - Greater understanding is needed of nonclinical factors that determine
      neurologists' decisions to order tests. The authors surveyed 595 US neurologists
      and utilized demographic information, attitude scales, and clinical scenarios to
      evaluate the influence of nonclinical factors on test-ordering decisions. Greater
      test reliance, higher malpractice concerns, and receiving reimbursement for
      testing were all associated with a higher likelihood of test ordering. These
      findings have implications for training needs and suggest malpractice worries may
      inflate health care costs.

PMID- 14718713
TI  - Pilot trial of 1-octanol in essential tremor.
AB  - 1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to
      inhibit tremor in essential tremor (ET) animal models at a much lower dose than
      ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial
      of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No
      significant side effects or signs of intoxication were observed. 1-Octanol
      significantly decreased tremor amplitude for up to 90 minutes. The results
      suggest 1-octanol as a well-tolerated and safe potential treatment for ET.
      Further trials are warranted.

PMID- 14718714
TI  - Evaluation of the pull test technique in assessing postural instability in
      Parkinson's disease.
AB  - Variability in pull test (PT) performance can lead to inadequate evaluation of
      postural instability in patients with Parkinson's disease (PD). Assessing 66 PTs
      by 25 examiners, at least two of four raters agreed that specific items were
      performed incorrectly for stance in 27.3%, for strength and briskness of the pull
      in 84.9%, for examiner's response in 36.4%, and for technique issues in 9.1%.
      Examiners were consistent in their errors, and only 9% of examinations were error
      free.

PMID- 14718715
TI  - Alpha-synuclein haplotypes implicated in risk of Parkinson's disease.
AB  - The authors examined four- and six-loci haplotype constructs (from five single
      nucleotide polymorphisms and three microsatellite regions) of the alpha-synuclein
      gene in patients with Parkinson's disease (PD) and controls in an ethnic Chinese
      population. Logistic regression analysis demonstrated an association of NACP-Rep1
      (p = 0.002) and L478 (p < 0.0001) with risk of PD after correction for the
      effects of age, sex, and the other polymorphic loci. Specific four-loci and six
      loci haplotypes were significantly associated with an increased or decreased risk
      of PD.

PMID- 14718716
TI  - Antigliadin antibodies in Huntington's disease.
AB  - The relevance of gluten sensitivity in sporadic and hereditary ataxia
      pathogenesis is unclear. The authors found high antigliadin antibody titers in 23
      of 52 (44%) patients with Huntington's disease (HD), suggesting a previously
      unrecognized association between HD and gluten sensitivity. The results further
      question "gluten ataxia" as a distinct disease entity and raise the possibility
      that antigliadin antibodies in ataxia and other neurodegenerative diseases may be
      an epiphenomenon, the mechanisms of which remain to be investigated.

PMID- 14718717
TI  - Respiratory muscle activity during REM sleep in patients with diaphragm
      paralysis.
AB  - The diaphragm is the main inspiratory muscle during REM sleep. It was
      hypothesized that patients with isolated bilateral diaphragm paralysis (BDP)
      might not be able to sustain REM sleep. Polysomnography with EMG recordings was
      undertaken from accessory respiratory muscles in patients with BDP and normal
      subjects. Patients with BDP had a normal quantity of REM sleep (mean +/- SD, 18.6
      +/- 7.5% of total sleep time) achieved by inspiratory recruitment of
      extradiaphragmatic muscles in both tonic and phasic REM, suggesting brainstem
      reorganization.

PMID- 14718719
TI  - Association between the tumor necrosis factor-alpha -308 G/A gene polymorphism
      and migraine.
AB  - In a group of 299 migraine patients and 306 control subjects, the association of
      the -308 G/A polymorphism in the tumor necrosis factor-alpha gene (TNFalpha) with
      the occurrence and clinical characteristics of migraine was tested. Homozygosity
      for the G allele was associated with an increased risk of migraine (odds ratio
      [OR] = 2.85, p < 0.001). When the patients were divided into subgroups, the
      association was confirmed in patients affected by migraine without aura (OR =
      3.30, p < 0.001) but not in migraine with aura. These data suggest that the
      TNFalpha gene or a linked locus significantly modulates the risk for migraine.

PMID- 14718718
TI  - Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis.
AB  - Idiopathic narcolepsy is associated with deficient hypocretin transmission.
      Narcoleptic symptoms have recently been described in paraneoplastic encephalitis
      with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six
      patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in
      patients with idiopathic narcolepsy. Anti-Ma autoantibodies were not detected in
      patients with idiopathic narcolepsy. Four patients with anti-Ma2 encephalitis had
      excessive daytime sleepiness; hypocretin-1 was not detectable in their
      cerebrospinal fluid, suggesting an immune-mediated hypocretin dysfunction.

PMID- 14718720
TI  - Absence of IgG1 response in the cerebrospinal fluid of relapsing neuromyelitis
      optica.
AB  - The authors studied immunoglobulin (Ig) G subclasses in the CSF and sera of
      patients with relapsing neuromyelitis optica (RNMO) and typical multiple
      sclerosis (MS). Although the total IgG concentrations were elevated in the CSF of
      patients with RNMO and MS, IgG1% and IgG1 index were significantly elevated only
      in patients with MS. The absence of the CSF IgG1 responses in the patients with
      RNMO may suggest less Th1 immunity and may also explain the rarity of oligoclonal
      IgG bands in patients with this disease.

PMID- 14718721
TI  - Recurrent transverse myelitis associates with anti-Ro (SSA) autoantibodies.
AB  - Transverse myelitis (TM) is an idiopathic inflammatory disorder of the spinal
      cord. The authors observed cases of recurrent TM in patients where anti-Ro (SSA)
      antibodies were present and therefore performed a case-control study to examine
      the frequency of anti-Ro autoantibodies in patients with recurrent TM and control
      subjects. Antibodies to 52-kd Ro were demonstrated in 77% of cases (10/13)
      compared with only 33% of control subjects (4/12).

PMID- 14718722
TI  - Pseudo-enhancement from polycythemia.

PMID- 14718723
TI  - Functional imaging in PNH caused by a new FilaminA mutation.

PMID- 14718724
TI  - ANCA-associated small vessel vasculitis presenting with ischemic optic
      neuropathy.

PMID- 14718726
TI  - Diaphragmatic paralysis due to isolated phrenic neuropathy in an HIV-infected
      man.

PMID- 14718725
TI  - Pharyngeal-brachial palsy after cytomegalovirus colitis.

PMID- 14718727
TI  - Rapid resolution of quadriplegic CIDP by combined plasmapheresis and IVIg.

PMID- 14718728
TI  - Sinking brain syndrome: craniotomy can precipitate brainstem herniation in CSF
      hypovolemia.

PMID- 14718729
TI  - Neuroprotective agents for clinical trials in Parkinson's disease: a systematic
      assessment.

PMID- 14718730
TI  - Amyloid beta 1-42 and tau in cerebrospinal fluid after severe traumatic brain
      injury.

PMID- 14718731
TI  - Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with
      Lewy bodies.

PMID- 14718732
TI  - Severe intoxication after phenytoin infusion: a preventable pharmacogenetic
      adverse reaction.

PMID- 14718733
TI  - Resident duty hours: the ACGME perspective.

PMID- 14718734
TI  - ACGME work hours regulations: a perspective from neurology program directors.

PMID- 14718736
TI  - Funding for retirement.

PMID- 14718737
TI  - Orthodontic treatment veneers.

PMID- 14718738
TI  - A simplified presurgical impression for evaluating arch compatibility.

PMID- 14718739
TI  - Facing retirement.

PMID- 14718740
TI  - 2003 JCO Orthodontic Practice Study. Part 3: Practice growth and staff data.

PMID- 14718741
TI  - A new bone screw for orthodontic anchorage.

PMID- 14718742
TI  - The Kilroy Spring for impacted teeth.

PMID- 14718743
TI  - Atherosclerosis and extracellular matrix.
AB  - Atherosclerosis is primarily a lesion that progresses due to a series of
      reactions that are induced by repair of injured intima. The intercellular
      networking that occurs among smooth muscle cells, macrophages, T lymphocytes and
      endothelial cells leads to a fibroproliferative response, in which the
      extracellular matrix (ECM) plays an important role. The ECM, composed of a
      mixture of vastly different macromolecules including collagen, elastin,
      glycoproteins and proteoglycans, confers tensile strength and viscoelasticity to
      the arterial wall. Each component of the ECM possesses unique structural
      properties that determine its own roles during the development of atherosclerotic
      plaques. Not only does the ECM provide the structural integrity of the plaques,
      but it also participates in several key events such as cell migration and
      proliferation, lipoprotein retention and thrombosis. The various matrix
      metalloproteinases (MMPs), major enzymes in ECM degradation, and their inhibitors
      (tissue inhibitors of MMPs) are demonstrated in plaque. An excess of MMPs over
      inhibitors contributes significantly to ECM destruction rendering the plaque more
      prone to rupture. Accumulating information on the molecular regulation of ECM
      synthesis and degradation will help investigators attain a more thorough
      understanding of the mechanisms of plaque formation and plaque instability and
      rupture.

PMID- 14718744
TI  - Role of matrix metalloproteinases in vascular remodeling.
AB  - Vascular remodeling, defined as lasting structural changes in the vessel wall in
      response to hemodynamic stimuli, plays a role in many (patho)physiological
      processes requiring cell migration and degradation of extracellular matrix(ECM).
      Matrix metalloproteinase(MMP) system can degrade most ECM components. Several
      lines of evidence support a role for MMP system components in the development and
      progression of atherosclerosis and restenosis after angioplasty. This review
      article focuses on the role of MMPs in vascular remodeling relevant to
      atherosclerosis and restenosis after angioplasty.

PMID- 14718745
TI  - Serum lipoprotein(a) concentration and Apo(a) isoform under the condition of
      renal dysfunction.
AB  - A serum lipoprotein(a) (Lp(a)) is an independent risk factor for cardiac events.
      It is well known that the patients with chronic renal failure (CRF) have a high
      concentration of serum Lp(a). The purpose of this study was to indicate the
      relationship between serum Lp(a) concentration and apoprotein(a) (apo(a))
      isoforms under the condition of renal dysfunction. One-hundred thirty patients
      having hypertension, hyperlipidemia, diabetes mellitus and/or CRF were selected
      in this study. All patients were divided into two groups according to the level
      of serum creatinine. Serum Lp(a) concentration in the CRF patients (Cr > 2.0
      mg/dl) was significantly higher than that in the controls (Cr < 1.2 mg/dl). Many
      CRF patients had high molecular weight (HMW)-apo(a). This study showed that the
      increase in HMW-apo(a) was closely accompanied by the increase in serum
      creatinine levels, and the serum Lp(a) concentration with HMW-apo(a) was higher
      according to their creatinine levels.

PMID- 14718746
TI  - Effects of margarine containing medium-chain triacylglycerols on body fat
      reduction in humans.
AB  - We found previously that the ingestion of margarine containing medium-chain
      triacylglycerols (MCT) resulted in a significant increase in postprandial
      thermogenesis when compared with long-chain triacylglycerols (LCT). Diets that
      included margarine containing MCT and LCT were compared for 12 weeks in 73
      subjects to investigate the effects on body weight, body fat, areas of
      subcutaneous and visceral fat, serum total cholesterols, triglycerides,
      lipoproteins, plasma glucose, serum insulin, total ketone bodies, and the
      activities of aspartate aminotransferase, alanine aminotransferase, and gamma
      glutamyltranspeptidase. We conducted a double-blind, controlled study and used
      blended rapeseed oil and soybean oil (LCT) as a comparison. Two groups ingested
      2100-2400 kcal/day of energy, 65-73 g/day of total fat, and 14 g/day of test
      margarine (5 g/day of MCT or LCT). The subjects on the MCT diet demonstrated
      significant decreases in body fat weight (- 3.8 +/- 2.4 kg vs - 2.4 +/- 1.7 kg;
      MCT vs LCT, mean +/- SD), subcutaneous fat (- 38.2 +/- 29.9 cm(2) vs - 22.6 +/-
      19.3 cm(2)), and visceral fat (- 12.2 +/- 11.2 cm(2) vs - 1.6 +/- 12.8 cm(2))
      after 12 weeks. There were no clinical differences in measured blood parameters.
      We suggest that the postprandial increase in thermogenesis and control of
      postprandial triglyceride levels may explain these results.

PMID- 14718747
TI  - Screening for familial combined hyperlipidemia in children using lipid
      phenotypes.
AB  - The purpose of this study was to screen for FCHL in children using serum lipid
      phenotypes. The subjects were 1190 (599 male, 591 female) children who
      participated in a screening and care program for life style-related diseases in
      school children. Total cholesterol, high-density lipoprotein cholesterol and
      triglyceride were determined, and information on the family history of parents
      was obtained by questionnaire. Candidates for FCHL were screened by the following
      criteria; type IIb hyperlipidemia, type IIa hyperlipidemia with positive family
      history of CHD, hyperlipidemia or both. We informed them of the results by mail.
      A second series of examinations to diagnose FCHL was performed on volunteer
      participants, including their parents. The candidates consisted of 9 children
      with type IIb and 27 with type IIa hyperlipidemia, 11 of whom participated, in
      the second series of examinations, in which 5 children were diagnosed with FCHL.
      The prevalence was 0.4%, suggesting that at least half of all individuals with
      FCHL already demonstrate hyperlipidemia in childhood.

PMID- 14718748
TI  - Global analysis of shear stress-responsive genes in vascular endothelial cells.
AB  - DNA microarray gene expression analysis was conducted in human umbilical vein
      endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs) exposed
      to laminar or turbulent shear stress. Approximately 3% of the total 5600 gene in
      HUVECs and HCAECs increased their expression more than two-fold or decreased it
      to less than half the static control in response to an arterial level of laminar
      shear stress (15 dynes/cm(2) for 24 hours). The proportions of shear-stress
      responsive genes decreased to around 2% under the venous level of laminar shear
      stress (1.5 dynes/cm(2)) in both cell lines. Turbulent shear stress of 1.5
      dynes/cm(2) altered the expression of 1.1% of all genes in the HCAECs. Laminar
      shear stress, but not turbulent shear stress, decreased the expression of a
      number of genes involved in DNA synthesis and the cell cycle in both HUVECs and
      HCAECs. Clustering analysis showed a variety of temporal profiles of gene
      expression in HUVECs exposed to laminar shear stress of 15 dynes/cm(2) for 3, 6,
      12, 24, and 48 hours. Turbulent shear stress affected expression of many genes
      that play a role in vascular remodeling, including genes encoding plasminogen
      activators and their inhibitor, endothelin-1, transforming growth factor-beta,
      collagen type IV, and ephrin A1.

PMID- 14718749
TI  - Clinical utility and approach to estimate postprandial hypertriglycemia by a
      newly designed oral fat-loading test.
AB  - The objective of this study was to estimate postprandial hypertriglycemia by a
      newly designed oral fat-loading test. Twenty-three healthy normolipidemic
      volunteers were orally administered a test meal consisting of a mixture of
      Telmeal 2.0 and 20 g of salt-free butter after fasting for 12 h. To measure the
      levels of total cholesterol (T-Cho), triglycerides (TG), high-density lipoprotein
      cholesterol (HDL-C), remnant-like particle-cholesterol (RLP-C), lipoprotein (a)
      [Lp (a)], free fatty acid, apolipoproteins (Apos), plasma glucose (PG),
      immunoreactive insulin (IRI), and high-sensitivity C-reactive protein (hs-CRP),
      venous blood samples were collected before the meal and at each hour until 9 h
      after fat-loading. The levels of both TG and RLP-C were drastically elevated at 2
      h after fat-loading and these levels remained high until 4 h (p < 0.01). A
      significant correlation between TG and RLP-C was also observed at 2, 3 and 4 h,
      and the values of the correlation coefficients (r) were 0.837, 0.838, and 0.908,
      respectively. In contrast, the levels of T-Cho, HDL-C, Lp (a), Apos, PG, and hs
      CRP did not change. Furthermore, there were no gastrointestinal symptoms during
      or after the study. These results strongly suggested that this newly designed fat
      loading test was very useful for evaluating postprandial hypertriglycemia,
      including remnant concentrations.

PMID- 14718750
TI  - A case of severe hyperlipidemia caused by long-term tube feedings.
AB  - A 77-year-old woman with type II diabetes mellitus was admitted to our hospital
      in August/ 1995 with severe hyperlipidemia. She had taken feedings through a
      nasogastric tube with 1000 ml (1000 kcal) of Ensureliquid daily since 1993
      because of the muscle weakness after rhabdomyolysis. Her serum total cholesterol
      was 515 mg/dl and triglyceride was 3378 mg/dl despite administration of 10 mg of
      simvastatin daily. After substitution of a standard diet starting August 21, we
      found significant decreases of total cholesterol from 725 mg/dl to 194 mg/dl and
      triglyceride from 4680 mg/dl to 550 mg/dl within 37 days. We also found a severe
      decrease in her serum total carnitine level of 22 micromol/l (normal range 45-91
      micromol/l) before changing the diet, suggesting secondary carnitine deficiency.
      Severe hyperlipidemia was reversed by changing the carnitine deficient diet
      (Ensureliquid) to a carnitine-containing diet. We suggested that the development
      of hyperlipidemia was related to the carnitine deficiency.

PMID- 14718751
TI  - Efficacy of serum nitric oxide level estimation in assessing the severity of
      necrotizing pancreatitis.
AB  - BACKGROUND: The role of nitric oxide in the pathophysiology of necrotizing
      pancreatitis is unclear. METHODS: In a prospective study, the clinical course of
      40 patients diagnosed as having acute necrotizing pancreatitis was followed using
      computed tomography severity score (CTSS) and serial APACHE II scoring. The serum
      nitric oxide levels in the form of reactive nitrogen intermediates (RNI) were
      estimated on admission and on day 3. Occurrence of complications, need for
      intervention, incidence of organ failure, and outcome were noted. The efficacy of
      CTSS, APACHE II scores, and RNI levels in predicting morbidity and mortality was
      assessed. The correlation between CTSS, APACHE II scores, and RNI levels was
      studied. RESULTS: The study group showed significantly higher levels of RNI as
      compared with the control group (159.1 vs. 106.0 nmol/ml, p < 0.05). The RNI
      levels were not affected by the occurrence of local complications or distant
      organ failure. The RNI levels on admission were significantly higher in the
      subset of patients who developed bacterial sepsis (195.5 vs. 134.7 nmol/ml, p <
      0.05). The RNI levels on admission in the non-survivors were higher as compared
      with those of the survivors (216.0 vs. 140.1 nmol/ml, p < 0.05). There was a
      significant positive correlation between the RNI levels and the CTSS in these
      patients (p < 0.05). There was no correlation between RNI levels and APACHE II
      scores. CONCLUSIONS: Acute necrotizing pancreatitis is associated with raised
      serum nitric oxide levels at its early stage. Patients with higher serum nitric
      oxide levels are at a significantly higher risk of sepsis and mortality.

PMID- 14718752
TI  - Renal dopamine and salt sensitivity of blood pressure in IgA nephropathy.
AB  - BACKGROUND: Patients with chronic glomerulonephritis exhibit salt-sensitive (SS)
      hypertension. In the early stage, however, the exact characteristics are still
      unclear. A decrease in renal dopamine production under basal conditions or after
      a sodium load has been reported in a subset of patients with SS primary
      hypertension. AIMS: The present study examined 17 untreated IgA-N patients with
      near-normal renal function, to determine whether salt sensitivity appears before
      hypertension and whether this sensitivity is related to renal dopamine
      production. METHODS: Daily urinary excretion of dopamine, the amine precursor--L
      DOPA, and metabolites was monitored in conditions of basal sodium ingestion,
      followed by three consecutive 5-day periods of 100, 20 and 350 mmol/day sodium
      intake. The sodium sensitivity index (SSI) was evaluated in each patient. In
      addition, the patients were considered SS when showing an increase > or =5 mm Hg
      in 24-hour mean BP when they changed from a 20- to a 350-mmol/day sodium diet.
      RESULTS: Urinary dopamine output was lower in SS than in salt-resistant patients
      throughout the study (p < 0.001). This was accompanied by lower creatinine
      clearance values and higher urinary protein excretion in SS IgA-N patients. A
      strong negative relationship was observed in these 17 IgA-N patients between the
      SSI and the daily urinary excretion of dopamine in conditions of both 20 mmol/day
      sodium intake (r2 = 0.592; p = 0.0003) and 350 mmol/day sodium diet (r2 = 0.352;
      p = 0.01). However, urinary dopamine output varied appropriately throughout the
      study in SS patients, in agreement with changes in sodium intake. CONCLUSION: We
      conclude that in IgA-N patients, a rightward shift in the 'pressure natriuresis'
      can appear before hypertension and is related with a reduced renal production of
      dopamine. It is suggested that decreased renal dopamine synthesis in SS IgA-N
      patients results from acquired tubulointerstitial injury. In contrast to what has
      been found in SS primary hypertension, renal dopamine may behave appropriately in
      SS IgA-N patients, as a compensatory hormone.

PMID- 14718753
TI  - Thrombolysis for ischemic stroke in patients with old microbleeds on pretreatment
      MRI.
AB  - BACKGROUND: Old asymptomatic microbleeds (MBs) visualized on T2-weighted MRI are
      indicative of microangiopathy. They may be a marker of increased risk of
      intracerebral hemorrhage (ICH) following thrombolysis. However, data regarding
      this potential risk are limited. METHODS: A retrospective analysis of
      pretreatment T2-weighted MRI was performed in consecutive stroke patients who
      received intravenous tissue plasminogen activator (tPA). We aimed to assess the
      impact of MBs on the risk of cerebral bleeding. The frequency and location of MBs
      were assessed and compared with the location of ICH after thrombolysis. RESULTS:
      Forty-four patients were studied. MBs were present on pretreatment MRI in 8 cases
      (18.2%). At day 1, symptomatic ICH occurred in none of 8 patients with MBs versus
      1 of 36 patients without (NS). At day 1, ICH occurred in 3 of 8 patients with MBs
      versus 10 of 36 patients without (NS). At day 7, symptomatic ICH occurred in 1 of
      8 patients with MBs versus 2 of 36 patients without (NS). At day 7, ICH occurred
      in 5 of 8 patients with MBs versus 12 of 36 patients without (NS). No ICH
      occurred at the site of an MB. ICH occurred within the ischemic area in all
      patients who bled. CONCLUSIONS: Our study suggests that stroke patients with a
      small number of MBs on pretreatment MRI could be treated safely with
      thrombolysis. Larger prospective studies are needed to address the predictive
      value of detection of MBs with regard to the risk of tPA-induced ICH.

PMID- 14718754
TI  - Progressing stroke: towards an internationally agreed definition.
AB  - BACKGROUND: The study of early neurological deterioration (progression) in acute
      stroke has been hampered by a lack of standardisation in the terminology or
      assessment procedures. An international panel was therefore convened, to agree on
      robust operational definitions for future studies and to validate them in an
      observational study involving 10 centres from the European Stroke Database
      Collaboration. METHODS: Standardised neurological assessments were performed
      daily for the first 3 days on patients with acute stroke, consecutively admitted
      within 24 h of onset, using the Scandinavian Stroke Scale (SSS) scoring system.
      An early deterioration episode (EDE) was defined as a >/=2 SSS-point worsening in
      either conscious level, arm, leg or eye movement scores, and/or a >/=3 SSS-point
      worsening in speech score, between consecutive neurological assessments. Stroke
      progression (SP) was defined as a similar neurological worsening comparing the
      day 3 assessment with the baseline assessment, or death occurring within 72 h of
      onset. The ability of SP to predict poor outcome (death or a Barthel ADL score
      <15/20 at 3 months), independently of initial stroke severity or other prognostic
      factors, was compared with possible alternative definitions, including one based
      on the Canadian Stroke Scale. RESULTS: The occurrence of EDEs and SP within the
      first 3 days of admission could be determined in 563 cases. EDEs occurred in 33%
      and SP in 26% of cases. Both were strong independent predictors of poor outcome.
      The prognostic efficiency of the European Progressing Stroke Study (EPSS)
      definition of SP was better than any of the alternatives examined, and clearly
      better than a definition based on changes in the total SSS score. CONCLUSIONS:
      The EPSS definitions of EDEs and SP have good construct and prognostic validity.
      They can be recommended as a standard for future studies on the aetiology and
      mechanisms of this common and important phenomenon.

PMID- 14718758
TI  - Better manage technology to boost safety.

PMID- 14718755
TI  - Fetal hypoxia is associated with elevated cord serum C-reactive protein levels in
      diabetic pregnancies.
AB  - Maternal diabetes increases the risk of intrauterine hypoxia. Inflammation may
      play a role in the pathogenesis of hypoxia-related neonatal complications. We
      studied correlations between levels of cord serum C-reactive protein (CRP),
      measured by a highly sensitive immunofluorometric assay, and indices of fetal
      hypoxia in diabetic pregnancies. Cord serum CRP correlated positively with
      amniotic fluid erythropoietin and umbilical artery pCO2. A negative correlation
      existed between cord serum CRP and umbilical artery pH and pO2. Amniotic fluid
      erythropoietin showed an independent effect on cord serum CRP in multiple
      regression analysis. These data suggest that the fetus responds to hypoxia by an
      inflammatory reaction.

PMID- 14718759
TI  - How safe is your environment of care?
AB  - JCAHO offers the latest tips on how to enhance safety in your department.

PMID- 14718760
TI  - To impact political policy, first prepare.
AB  - Learn how to get involved politically and lobby effectively.

PMID- 14718761
TI  - Add coaching to your leadership repertoire.

PMID- 14718762
TI  - Nurses: nurture your young.

PMID- 14718763
TI  - Get the edge on deep vein thrombosis.
AB  - Review practical DVT screening considerations to enhance assessment skills.

PMID- 14718764
TI  - Defy the decades with multigenerational teams.
AB  - Identify techniques for relating to staff members of any age.

PMID- 14718765
TI  - Cultivate corporate culture and diversity.
AB  - Elements of teamwork; commitment; and multiple, diverse workforces comprise a
      healthy organization, evident by the behaviors and attitudes of its employees.

PMID- 14718766
TI  - The Magnetic pull.
AB  - Nursing Management profiles a number of hospitals that attained Magnet status
      from the American Nurses Credentialing Center.

PMID- 14718767
TI  - Interventional cardiology: a nurse manager's perspective.
AB  - Invasive cardiac care measures improve patient outcomes and challenge
      departmental budgets.

PMID- 14718768
TI  - Home testing: friend or foe?
AB  - Though more patients seek out home tests, nurses find pros and cons associated
      with their use.

PMID- 14718769
TI  - Think cooperation, not competition.
AB  - Neighboring hospitals can offer a wealth of information to help you start a new
      program at your facility.

PMID- 14718770
TI  - Thought disorder in schizophrenia: working memory and impaired context.
AB  - This research was designed to provide data on whether thought disorder in
      schizophrenia patients is due to difficulty in holding external stimuli or the
      external context online in working memory. We assessed 231 early phase acute
      inpatients, including 68 schizophrenic patients and 38 bipolar manic patients.
      Patients were administered a thought disorder test that requires holding stimuli
      online in working memory as they respond and another in which the stimuli is in
      direct view of the patients throughout the test procedure. The results indicated
      that patients who were thought disordered on the test requiring holding the
      external stimuli online in memory also were more thought disordered on the test
      that provides full vision of the stimuli throughout the testing (p < 0.001).
      Thus, schizophrenia patients vulnerable to thought disorder show thought disorder
      regardless of whether or not they are required to hold the stimuli online in
      memory. Overall, the data did not support the formulation that thought disorder
      is primarily a consequence of failure to hold external stimuli or contextual
      material online in working memory. An alternate view of thought disorder is
      presented.

PMID- 14718772
TI  - Serious cardiovascular events and mortality among patients with schizophrenia.
AB  - This study compared the risks of cardiovascular morbidity and mortality in people
      with schizophrenia who use antipsychotic medications to risks in individuals
      without schizophrenia in a large managed care organization. A sample of 1920
      schizophrenia patients was matched by age, sex, date, and health plan to 9600
      persons randomly selected from the health plan general membership. Death,
      myocardial infarction, arrhythmia, and new-onset diabetes were identified using a
      National Death Index search and medical claims records. The adjusted all-cause
      mortality rate in the group of treated schizophrenics was four times higher than
      in the control group regardless of whether patients were given a typical or an
      atypical antipsychotic medication. Users of typical antipsychotics had a fivefold
      higher risk of myocardial infarction than the control subjects. Among patients
      with schizophrenia, cardiovascular risk was inversely associated with intensity
      of use of antipsychotic drugs, suggesting that the observed risks may not be due
      to a simple or direct effect of drugs. Patients treated for schizophrenia had
      higher rates of new-onset diabetes than did the general population controls. This
      risk was most pronounced in persons with more intense exposure to drugs and
      appeared to be indistinguishable in users of typical antipsychotics, of atypical
      products, or of both.

PMID- 14718771
TI  - Theory of mind performance in schizophrenia: diagnostic, symptom, and
      neuropsychological correlates.
AB  - The purpose of this study was to explore the relationship between Theory of Mind
      (ToM) performance and schizophrenia subtype, symptom, and neuropsychological
      variables. One hundred twenty-eight stable outpatients with schizophrenia or
      schizoaffective disorder were assessed during the intake phase of a vocational
      and cognitive rehabilitation study. Results indicate that ToM performance
      differed significantly by schizophrenia diagnosis, with people diagnosed with
      disorganized schizophrenia performing the most poorly. Theory of Mind performance
      was also significantly correlated with measures of thought disorder and verbal
      memory. Regression analysis revealed that thought disorder and verbal memory
      measures explained 30% of the variance in ToM scores. Findings suggest that there
      is theory of mind variance in the schizophrenia population and theory of mind is
      strongly related to thought disorder, verbal memory, and cognitive
      disorganization. Contrary to previous reports, ToM was not related to measures of
      paranoia.

PMID- 14718773
TI  - Schizotypy: a vulnerability factor for traumatic intrusions.
AB  - Intrusive mental experiences occur within posttraumatic stress disorder (PTSD)
      and some psychotic disorders. Similarities in the phenomenology and content in
      the intrusions of both disorders have been noted. Currently there is little
      understanding of any common etiology in terms of information-processing styles.
      This study investigated predictors of analogue posttraumatic intrusive cognitions
      within a nonclinical sample, including schizotypy, dissociation, and trauma
      history. Forty-two participants watched a trauma video and recorded trauma
      related intrusions occurring for 1 week. More reported intrusive experiences were
      associated with high positive symptom schizotypy. Our findings are discussed in
      relation to the possible role of trauma-related intrusions within psychotic
      disorders.

PMID- 14718774
TI  - Long-term course of treatment-seeking Vietnam veterans with posttraumatic stress
      disorder: mortality, clinical condition, and life satisfaction.
AB  - This study is a 6-year longitudinal study of 51 treatment-seeking male veterans
      with combat-related posttraumatic stress disorder. Measures of PTSD and
      psychiatric symptomatology, social functioning, and program impact were assessed
      at admission to an inpatient treatment program, at 18 months, and 6 years later.
      Previous studies had shown that the treatment program's impact on course of
      illness had been negligible. The sample showed an extremely high mortality rate
      of 17% over 6 years. The remaining veterans showed improvement in violence and
      alcohol and drug use, but an increase in hyperarousal symptoms and social
      isolation. Nearly three-fourths had had an inpatient hospitalization. Veterans'
      self-ratings, in contrast, indicated significant improvement in all areas of
      functioning except employment, as well as an overall positive view of the impact
      of the program on their lives. Results indicate that the majority of the veteran
      sample had experienced some improvement in their ability to cope with their
      chronic illness, decreasing their use of violence and substance abuse but still
      were experiencing high levels of symptomatology. The extremely high mortality
      rate, however, provides a somber reminder of the seriousness of this disorder.

PMID- 14718775
TI  - The Hawaii Vietnam Veterans Project: is minority status a risk factor for
      posttraumatic stress disorder?
AB  - The Hawaii Vietnam Veterans Project (HVVP) was congressionally mandated as a
      follow-up to the National Vietnam Veterans Readjustment Study (NVVRS) to assess
      current and lifetime prevalence of posttraumatic stress disorder (PTSD). The
      Hawaii Vietnam Veterans Project used the original two-stage NVVRS design in which
      a lay interview, conducted with a large sample, was followed by a clinical
      interview with a smaller subsample. Reported results are from the clinical
      subsample consisting of 100 Native Hawaiian and 102 American of Japanese ancestry
      veterans compared with white veterans from the NVVRS cohort. The major finding is
      that veterans of Japanese ancestry exhibited significantly lower prevalence of
      current full, current partial, and lifetime full PTSD than white veterans.
      Adjustment for age and war zone exposure did not eliminate most of these
      differences. These results indicate that minority status per se is not a risk
      factor for PTSD.

PMID- 14718776
TI  - Does caregiving stress affect cognitive function in older women?
AB  - Increasing numbers of women provide care to their ill spouses; however, no
      studies have examined possible effects of caregiving stress on cognitive
      function. We administered 6 tests of cognitive function to 13740 Nurses' Health
      Study participants aged 70-79 years. We collected information on caregiving and
      numerous potential confounding variables via biennial mailed questionnaires.
      After adjustment for potential confounders (age, education, mental health index,
      vitality index, use of antidepressants, and history of high blood pressure,
      diabetes, and heart disease), we found modest but significantly increased risks
      of low cognitive function on three of the cognitive tests among women who
      provided care to a disabled or ill spouse compared with women who did not provide
      any care. For example, on the TICS, a test of general cognition, the risk of a
      low score was 31% higher in women who provided care compared with women who did
      not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor
      performance on several cognitive tests among women who provided care to their
      disabled or ill husbands.

PMID- 14718777
TI  - Brazilian patients with panic disorder: the use of defense mechanisms and their
      association with severity.
AB  - This study aims to evaluate the defense mechanisms most frequently used by
      Brazilian patients with panic disorder when compared with a control group. The
      study also examines the association between severity of disease and comorbidity
      and the use of specific defense mechanisms. Sixty panic-disordered patients and
      31 controls participated in the study. The Mini International Neuropsychiatric
      Interview was used to confirm the panic disorder diagnosis and to establish the
      comorbid diagnosis. The Clinical Global Impression (CGI) was used to assess
      severity and the Defensive Style Questionnaire (DSQ-40) was used to evaluate the
      defense mechanisms. Panic patients used more neurotic (mean = 4.9 versus 3.6; p <
      0.001) and immature (mean = 3.9 versus 2.8; p < 0.001) defenses as compared with
      controls. Panic patients with severe disease (n = 37; CGI>4) had more depression
      comorbidity and used more immature defenses than patients with CGI<or=4 (n = 23;
      mean = 4.2 versus 3.5; p < 0.001). It was concluded that the panic severity and
      depression comorbidity found in Brazilian panic-disordered patients are
      associated with the use of maladaptive mechanisms, namely immature defenses.

PMID- 14718778
TI  - Characterizing the long-term course of individuals with major depressive
      disorder.

PMID- 14718779
TI  - Role of fantasy proneness, imaginative involvement, and psychological absorption
      in depersonalization disorder.

PMID- 14718780
TI  - Cognitive and psychiatric aspects of Huntington disease contribute to functional
      capacity.

PMID- 14718781
TI  - Elderly veterans with combat-related posttraumatic stress disorder in specialty
      care.

PMID- 14718783
TI  - President's Address: Minimally invasive treatment for patients with early breast
      cancer.

PMID- 14718784
TI  - Breast cancer in Russia.

PMID- 14718785
TI  - Current status of antibody therapy for breast cancer.
AB  - Antibody therapy with trastuzumab has greatly impacted breast cancer treatment.
      Combination treatment with trastuzumab is regarded currently as a first-line
      therapy for metastatic breast cancers that overexpress Her-2. It has become
      routine practice to examine the status of Her-2 expression in primary tumors. The
      impact of this therapy might be as great as that of endocrine therapy from a
      historical point of view. A number of new approaches using trastuzumab for
      seeking individualized treatment are being tested in current clinical trials. We
      reviewed recent advances in trastuzumab treatment and discuss the future of
      antibody therapy for breast cancer.

PMID- 14718786
TI  - The endocrine management of postmenopausal women with early breast cancer.

PMID- 14718787
TI  - Controversies in sentinel node biopsy for breast cancer.
AB  - Sentinel node biopsy for breast cancer patients has recently been applied as a
      less invasive, highly accurate alternative to axillary lymph node dissection.
      Numerous studies have shown that sentinel nodes accurately diagnose axillary
      staging. However, many problems remain to be answered and must be addressed
      before sentinel node biopsy becomes the standard surgical procedure for patients
      with breast cancer. We reviewed and discussed here three of these problems;
      axillary sampling as an alternative to sentinel node biopsy, dye method vs.
      combination of dye and radiocolloid for sentinel node biopsy, and intraoperative
      sentinel node examination. Further investigation will continue to be necessary as
      we learn how to better provide procedure of sentinel node biopsy.

PMID- 14718788
TI  - Brain metastasis of breast cancer.

PMID- 14718789
TI  - Collaboration of breast cancer clinic and genetic counseling division for BRCA1
      and BRCA2 mutation family in Japan.
AB  - BACKGROUND: BRCA1 and BRCA2 mutations cause high breast cancer incidence rates as
      high as 80% Although prophylactic therapy is still controversial, several
      prophylactic therapies have been proposed and tried for BRCA1 and BRCA2 mutation
      carriers. Prophylactic surgery, chemo-prevention and precise screening have been
      proposed as prophylactic therapy. All BRCA1 and BRCA2 mutation carriers need
      knowledge about their disease and the countermeasures that are used to protect
      against onset of disease. Counseling plays an important role in this regard for
      people with genetic diseases. Therefore, collaboration between breast cancer
      clinics and genetic counseling services is the most important issue in clinical
      practice. Our group consists of three national universities and a general
      hospital. In this article we describe our trial to construct a clinical system
      against hereditary breast cancer as an interim report for the Japanese Ministry
      of Health, Labour and Welfare. PATIENTS AND METHODS: Twenty familial breast
      cancer patients were registered in this study. The whole sequence of BRCA1 and
      BRCA2 were analyzed. If pathological mutations were detected, their first degree
      families were introduced to the counseling division at each institute when
      candidates visited counseling divisions. RESULTS AND DISCUSSION: Four cases of a
      deleterious mutation in BRCA1 or BRCA2 were detected among 20 cases. Their first
      degree relatives are now under consideration for visiting counseling divisions.
      The clinical system described in this study should play a role to protect BRCA1
      or BRCA2 mutation carriers in Japan.

PMID- 14718790
TI  - p33ING1b and estrogen receptor (ER) alpha.
AB  - The ING1 gene was originally cloned as a candidate tumor suppressor of human
      breast cancer, and recent studies suggest that ING1 proteins are involved in
      chromatin remodeling functions via physical association with both histone
      acetyltransferases (HATs) and histone deacetylases (HDACs). Both CREB binding
      protein (CBP) and the related p300 proteins show a marked preference for binding
      to complexes containing p33ING1b, one of the major ING1 isoforms, whereas HDAC
      immunocomplexes contain equal amounts of p33ING1b and p47ING1a. This observation
      is interesting, given that p33ING1b can selectively increase histone H3 and H4
      acetylation when micro-injected into individual cells, whereas p47ING1a inhibits
      histone acetylation. We investigated whether p33ING1b modulated the
      transcriptional activity of estrogen receptor (ER)alpha. In cells transfected
      with increasing concentrations of a mammalian expression vector encoding
      p33ING1b, estrogen-induced ER alpha transcriptional activity was found to
      increase in a dose-dependent manner. As p33ING1b expression levels increased,
      transcription of an ER-responsive reporter gene by either estrogen-inducible full
      length ER alpha or the activation function (AF) 1 deletion mutant was enhanced,
      while the AF2 deletion mutant was unaffected by the presence of p33ING1b. These
      results showed that p33ING1b enhanced estrogen-induced ER alpha activity through
      the AF2 domain. Our data demonstrate that p33ING1b acts like a coactivator for ER
      alpha and stimulates estrogen-induced ER alpha transcriptional activity
      consistent with a function for p33ING1b in chromatin remodeling.

PMID- 14718791
TI  - Inhibition of HER1 signaling pathway enhances antitumor effect of endocrine
      therapy in breast cancer.
AB  - Epidermal growth factor receptor (EGFR)/HER1 is expressed at high levels in at
      least 20% of breast cancers. This high expression correlates with a poor
      prognosis in patients with breast cancer. Experimental and clinical findings
      suggest that aberrant activation of tyrosine receptor kinases, such as HER1
      pathway, play a causal role in the development of antiestrogen resistance in
      breast cancer. Recent preclinical and clinical evidence shows that inhibition of
      growth factor signaling pathways suppresses the growth of malignant cells without
      serious toxicities. To test the hypothesis that inhibition of the HER1 signaling
      pathway enhances the antitumor effect of endocrine therapy, a promising signal
      transduction inhibitor (STI) of HER1 tyrosine kinase, gefitinib, and an estrogen
      receptor (ER) antagonist, fulvestrant, were administered to human breast cancer
      cells. Our experimental results have revealed that gefitinib additively enhances
      the antitumor effect of fulvestrant in estrogen receptor (ER)-positive breast
      cancer cells under estrogen-supplemented conditions. An additive increase in the
      protein expression level of a cyclin-dependent kinase inhibitor, p21 may play a
      key role of this additive cytostatic effect. The rationale and future
      perspectives of the combined use of STIs with endocrine therapy in breast cancer
      are discussed.

PMID- 14718792
TI  - Current progress in the prediction of chemosensitivity for breast cancer.
AB  - Advances in chemotherapy have improved the prognosis of patients with breast
      cancer significantly. Individualization is important for optimization of
      chemotherapy. The prediction of tumor sensitivity to anticancer agents has been
      intensively investigated for that purpose. There have been 2 approaches to
      predict the efficacy of drugs against individual tumors, drug-sensitivity tests
      and molecular marker genes. Although some of these tests are already available
      clinically, the prediction of chemosensitivity remains a goal to be achieved.
      Several studies with microarrays revealed that comprehensive analyses of genes
      may provide useful information for determining the chemosensitivity of cancer. We
      have started to use a cDNA microarray to study the chemosensitivity of breast
      cancer. Taken together with recent data, studies for drug sensitivity should
      provide insights into the mechanisms of drug sensitivity and the optimal design
      of more effective treatment strategies in breast cancer.

PMID- 14718793
TI  - What is the predictor for invasion in non-palpable breast cancer with
      microcalcifications?
AB  - PURPOSE: To assess the presence of invasion in non-palpable breast cancer with
      microcalcifications. MATERIAL AND METHODS: We investigated 157 patients with non
      palpable breast cancer with microcalcifications, who had undergone stereotactic
      core biopsy or vacuum-assisted breast biopsy and operation at the Cancer
      Institute Hospital between 1995 and 2001. We investigated the correlation between
      the area of calcification (maximum range of microcalcifications measured in mm by
      direct mammography), morphology of calcification on mammography, histological
      subtype of intraductal carcinoma (comedo or non-comedo) and frequency of
      invasion, and lymph node metastasis. The chi-square test was used in the
      statistical analysis and p values less than 0.05 were considered statistically
      significant. RESULTS: Invasion was observed in 33 of 157 pts (21%), of whom 23
      showed minimal invasion, which is less than 0.5 cm in greatest diameter. The risk
      of invasion was 13% within 10 mm of the microcalcifications (n =70), 25% from 11
      to 30 mm (n =59), and 32% more than 31 mm from the microcalcifications (n =28).
      The risk of invasion was 16% for punctate-round and amorphous type (n =87)
      microcalcifications, and 27% for pleomorphic and linear-branching types (n =70)(p
      =0.092). In addition, invasion was found 10% of the time within 10 mm of punctate
      round and amorphous type microcalcifications, and 20% of the time at 11 mm or
      more. On the other hand, invasion was found 15% of the time within 10 mm of
      pleomorphic and linear-branching type microcalcifications, and 37% of the time at
      11 mm or more. In 72 cases of intraductal carcinoma diagnosed by pathological
      examination, invasion was found in 10 of 31 (32%) comedo type intraductal
      carcinomas and in 5 of 41 (12%) non-comedo types (p =0.0379). There were 5 cases
      (3.2%) with axillary lymph node metastasis, all of which widely extended more
      than 21 mm from the microcalcifications. CONCLUSION: The risk of invasion was 10%
      within 10 mm of punctate-round and amorphous type microcalcifications, and 37% at
      more than 11 mm of pleomorphic, linear-branching microcalcifications.

PMID- 14718794
TI  - Magnetic resonance imaging of the metal clip in a breast: safety and its
      availability as a negative marker.
AB  - PURPOSE: This study assesses magnetic resonance (MR) safety of the stainless
      steel clip inserted after stereotactic-guided directional vacuum-assisted biopsy
      (DVAB) of the breast, and evaluates its imaging value. METHODS: We used a sausage
      as a substitute breast and inserted the clip into it. The MR images of the
      substitute were scanned using a breast coil, and it was then dissected. After the
      substitute experimentation, MR scanning of the breast was performed using a
      dynamic contrast enhanced technique, in which a clip was placed after DVAB for
      suspicion of ductal carcinoma was seen as grouped amorphous calcifications on
      mammography. RESULTS: On every magnetic resonance image of the substitute, the
      clip was seen as a spotty signal void, with no surrounding artifact. There was no
      movement and no evidence of increased clip temperature on dissected of the
      substitute, confirming the safety of breast MR with a clip in place. There was no
      patient complaint of feeling heat or pain during the MRI examination and there
      were only biopsy scars on the surgically excised breast specimen material. On the
      breast MR images, a spreading region of the tumor adjoining the position of the
      signal void was identified as an early enhancing lesion. CONCLUSIONS: The safety
      and reliability of breast MR examination using a mammotome clip was demonstrated
      by both the mock examination and the breast examination. It is possible to
      localize of tumor spread regions based on the marker position using the clip as a
      negative signal marker.

PMID- 14718795
TI  - FDG-PET for evaluation of recurrent lymph node metastases in patients with
      surgically resected breast cancer: adding spot images to whole body images.
AB  - BACKGROUND: To evaluate the role of 18F-Fluorodeoxyglucose positron emission
      tomography (FDG-PET), spot images were added to whole-body FDG-PET images in a
      patient with suspected lymph node recurrence of breast cancer. METHODS: FDG-PET
      spot images were obtained of 44 patients who had undergone surgical resection of
      breast cancer as were whole-body FDG-PET images. A total of 33 lesions in 19
      patients (mean age, 59 years; range, 39-70 years) were diagnosed as lymph node
      recurrence clinically, and standardized uptake values (SUVs) were calculated for
      whole body images and spot images. Lesions were also scored from 1 (not clear) to
      3 (very clear) for both the whole body and spot images. RESULTS: For mediastinal
      lymph node metastases, the SUVs of the spot images (SUVsp) (mean, 4.0; range, 2.1
      6.6) were significantly higher than the SUVs of the whole body images (SUVwb)
      (mean, 3.3; range, 2.1-5.8). For other lymph node metastases (neck, axilla,
      etc.), there was no significant difference between SUVwb (2.6; 1.4-6.5) and SUVsp
      (2.8; 1.6-8.1). CONCLUSIONS: By adding spot images, the evaluation of lymph node
      metastases became easier. Adding spot images to whole-body FDG-PET may be useful.

PMID- 14718796
TI  - Examination of breast conserving therapy in lobular carcinoma.
AB  - BACKGROUND: Experience with conserving surgery for lobular carcinoma has grown as
      more breast conserving surgeries have been performed. We examined the results of
      breast conserving therapy in lobular carcinoma. PATIENTS AND METHODS: We examined
      the postoperative positive margin rate, presence or absence of additional
      surgery, presence or absence of local or systemic recurrence and role of breast
      helical CT in 25 cases of breast conserving surgery performed at this department
      from 1991 through June 2003. RESULTS: Among the 303 cases of all breast
      conserving surgeries, there were 63 case with positive margins (20.8%), but there
      were 15 of 25 positive margin cases (60.0%) among the lobular carcinoma cases. In
      8 of the 15 positive margin cases the technique was changed to mastectomy. One
      case of recurrence in the breast has been observed thus far. Although the
      positive margin rate and positive margin rate in infiltrating carcinoma cases
      tended to decline after the introduction of breast helical CT, the rates remained
      high. CONCLUSIONS: Since the positive margin rate was significantly high at the
      time of breast conserving surgery for lobular carcinoma, careful selection of
      technique based on imaging studies such as breast helical CT and MRI along with
      careful follow-up is considered necessary.

PMID- 14718797
TI  - Current status and goals of mammographic screening for breast cancer in Japan.
AB  - In Europe and the United States, the proportion of women receiving mammographic
      screening for breast cancer has increased to 60-80%, resulting in an increase in
      the detection of early-stage cancer and a reduction in the mortality rate. The
      objectives of breast cancer screening have thus already been achieved there. In
      Japan, both the incidence and mortality of breast cancer have increased recently.
      Breast cancer screening has long been performed by clinical breast examination
      (CBE) alone. A reduction in the mortality of breast cancer cannot be expected
      from CBE. Mammographic screening for breast cancer was recommended in a
      notification issued by Ministry of Health, Labour and Welfare in 1999. An
      important aspect of mammographic screening is quality control. The Central
      Committee on Quality Control of Mammographic Screening(Central Committee)was
      organized by six screening-related societies, and attempts have since been made
      to establish a quality control system. Both the social recognition of the Central
      Committee and its cooperation with the "Quality Control Committee " of each
      community will become important. The cover rate of nationwide breast cancer
      screening by CBE alone is 12-13%, while the implementation rate of mammographic
      screening is presently very low and its cover rate is considered to be about 2%.
      With such a low cover rate, it is absolutely impossible to reduce the mortality
      of breast cancer. To achieve this, the administration and clinicians will be
      required to cooperate with each other to increase the spread and cover rate of
      high-quality mammographic screening.

PMID- 14718798
TI  - Mechanism of taxane neurotoxicity.
AB  - The two taxanes (paclitaxel and docetaxel) are widely employed in standard
      antineoplastic practice. Although these agents are now well established, some
      toxic side effects have been reported. Toxicity of these agents includes bone
      marrow suppression (principally neutropenia), hypersensitivity reactions,
      cutaneous reactions, edema and neurotoxicity. The most prominent neurotoxicity is
      a sensory neuropathy. Controlling neuropathy is crucial for maintaining the
      quality of life of patients because it is usually persistent and hard to manage.
      The precise mechanism for taxane-induced neuropathy is still unknown. The taxanes
      are known to promote aggregation of intracellular microtubules. Abnormal
      aggregation of microtubules in the neuronal cells may cause this neuropathy. In
      addition, the taxanes have been suggested to have intrinsic toxicity and directly
      injure the cells. A better understanding of the mechanism for this neuropathy may
      improve the quality of life of patients who undergo taxane antineoplastic
      therapy.

PMID- 14718799
TI  - Techniques for the neurological examination of taxane-induced neuropathy.
AB  - Taxanes are considered to be the key drugs in the treatment of breast cancer.
      Although physicians who treat patients with breast cancer have rarely seen
      patients with neuropathy as an adverse effect of treatment before the advent of
      taxanes, patients with breast cancer who are treated with taxanes frequently
      exhibit peripheral neuropathy. As peripheral neuropathy often causes
      deterioration of the quality of life of patients, it is very important to
      precisely assess the extent of peripheral neuropathy at an early stage. Clinical
      oncologists should be familiar with the techniques of neurological examination.
      In this article we describe the basic techniques for the neurological examination
      of patients with taxane-induced peripheral neuropathy. In the hope of
      facilitating the precise evaluation of taxane-induced peripheral neuropathy, the
      items of neurological examinations in this article are described with reference
      to the physician neuroexamination form (PNEF) designed by BioNumerik
      Pharmaceuticals Inc.

PMID- 14718800
TI  - Neurotoxicity of taxanes: symptoms and quality of life assessment.
AB  - Paclitaxel (TXL) and docetaxel (TXT), especially TXL, cause neurotoxicity
      manifested as polyneuropathy. In clinical practice, detailed knowledge of the
      symptoms and effect on quality of life (QOL) of neurotoxicity is crucially
      important both for diagnosis of neuropathy and for management of patients treated
      with taxanes. In this review, we summarize the symptoms of neurotoxicity caused
      by taxanes, and highlight the importance of QOL assessment in breast cancer
      patients treated with taxanes. The most common feature of taxane neurotoxicity is
      a predominant sensory distal neuropathy, and the incidence and severity of the
      neuropathic manifestations appear to be related to dose level and cumulative
      dose. A mixture of paresthesias and dysesthesias is often prominent, and the
      complaints include burning dysesthesia, numbness, tingling, and shooting pains,
      typically in a stocking-glove distribution. In contrast to sensory disturbances,
      motor neuropathy is not well recognized, and is believed to be much less common
      than sensory neuropathy. Weakness is usually mild, and distal motor neuropathy
      caused by taxanes rarely affects patients' activities of daily living. The effect
      of neurotoxicity on QOL is not fully understood, as no study has specifically
      assessed QOL in terms of neurotoxicity. There is therefore a clear need to
      collect more detailed data about QOL using well validated, reliable instruments.
      This will enable us to provide the information that patients require when
      treatment decisions are being made, and will help in the pursuit of the
      ameliorative interventions.

PMID- 14718801
TI  - Treatment and care of neurotoxicity from taxane anticancer agents.
AB  - Taxane anticancer agents play a central role in drug therapy for breast cancer
      today; however, they have a dose-limiting neurotoxicity that is difficult to
      prevent and treat. To protect against this neurotoxicity it is important to avoid
      large doses greater than 200 mg/m2, and to adopt 24-hour administration regimens.
      Care is also needed with regard to the cumulative dose. Glutamine and
      amitriptyline are two of the very few drugs that have been found to be clinically
      effective against drug-induced peripheral neuropathy. Drugs are discontinued if
      neuropathy appears. If administration is to be later restarted, it is recommended
      that combined use of glutamine or amitriptyline be considered and that patients
      be given guidance for daily life.

PMID- 14718802
TI  - Presidential address: SVS and AAVS united.

PMID- 14718803
TI  - Society for Vascular Surgery Distinguished Service Award--2003.

PMID- 14718804
TI  - A statewide experience with endovascular abdominal aortic aneurysm repair: rapid
      diffusion with excellent early results.
AB  - OBJECTIVE: The purpose of this study was to compare survival and outcomes of
      endovascular versus open repair of abdominal aortic aneurysms (AAAs) in New York
      State (NYS). METHODS: We used the NYS discharge dataset Statewide Planning and
      Research Cooperative System (SPARCS) to analyze the outcomes of elective
      admission for nonruptured (International Classification of Diseases-9th revision
      [ICD-9] 441.4) open aneurysm repair (38.44) and endovascular aneurysm repair
      (39.71) during the years 2000-2002. The ICD-9 code for endovascular repair was
      introduced in late 2000, thus capturing 3 months of empiric data for 2000.
      RESULTS: There has been a significant increase in the number of AAA procedures
      performed in NYS (comparing before and after 2000: average, 1419 vs 1701; P
      =.0001), temporally coinciding with the implementation of training programs after
      US Food and Drug Administration approval of endovascular grafts and the new
      payment code. From 2000 to 2002 the number of NYS hospitals performing
      endovascular repairs increased from 24 to 60. By 2002 there were more
      endovascular repairs being performed than open repairs (871 vs 783). The target
      population for these surgical interventions showed interesting differences. In
      2002, women had a 43% chance of receiving an endograft, whereas men had a 55%
      probability. The use of endovascular repair over the observation period was
      relatively constant in patients younger than 65 years. In patients older than 65
      years, and especially those older than 75 years, endovascular use increased
      substantially, so that by 2002 older patients were more likely to undergo
      endovascular repair than open repair. Patients who underwent endovascular repair
      had significantly more hypertension, coronary artery disease, diabetes, and
      hyperlipidemia than did patients who underwent open repair. Yet the mean length
      of stay for endovascular procedures was approximately 3.6 days, and for open
      procedures was about 10.3 days, across all 3 years (P = <.0001). Moreover,
      patients who underwent endovascular repair had statistically fewer postoperative
      complications and significantly lower mortality. In-hospital mortality in 2001
      was 3.55% for open repair and 1.14% for endovascular repair (P =.0018), and in
      2002 these rates were 4.21% versus 0.8% (P <.0001), respectively. CONCLUSION:
      This dataset suggests that endovascular AAA repairs are being performed in a
      patient population with a higher frequency of comorbidities. However,
      endovascular repairs still are associated with significantly lower in-hospital
      mortality, fewer postoperative complications, and a dramatically shorter length
      of stay. These results suggest that, despite the rapid diffusion of this new
      technique, early perioperative outcomes may be superior to those with
      conventional open repair. However, prospective clinical studies are needed to
      confirm these insights, and such studies may require the infrastructure of
      consortia of hospitals or society-based registries.

PMID- 14718806
TI  - Influence of endograft oversizing on device migration, endoleak, aneurysm
      shrinkage, and aortic neck dilation: results from the Zenith Multicenter Trial.
AB  - BACKGROUND: Generous endograft oversizing has been associated with propensity for
      aortic neck dilation and subsequent device migration in endografts without
      suprarenal fixation. Effects of variable oversizing of endografts with suprarenal
      fixation have been poorly studied. METHODS: Three hundred fifty-one patients
      underwent endovascular AAA repair (EVAR) in a prospective multicenter trial using
      the Zenith AAA Endovascular Graft, a fully supported bifurcated 3-piece endograft
      with barb-enhanced suprarenal stent fixation. Blinded core-laboratory measurement
      of variables was prospectively recorded at predischarge and at 1, 6, 12, and 24
      months after the procedure. Potential influence of endograft oversizing on
      subsequent aortic neck dilation (minor axis), aneurysm shrinkage (major axis),
      device migration, endoleak, rupture, open conversion, and death were
      retrospectively studied. Data are given as mean +/- SEM. RESULTS: Risk of
      endograft migration (>5mm) at 12 months was 2.3% (6/261). However, patients with
      endograft oversizing of >30% had a 14% (4/29) migration risk compared with those
      oversized < or =30% (0.9%, 2/232), P <.002. There was zero device migration by
      the SVS definition (>10 mm or clinical event). Device oversizing >30% was
      associated with decreased AAA sac shrinkage (48% vs 77%) and with increased sac
      enlargement (9.5% vs 0.6%) at 24 months when compared with oversizing of < or
      =30%, respectively (P =.001). Incidence rate of any endoleak at 12 and 24 months
      was 8.2% (21/256) and 7.1% (12/169), respectively. Oversizing of endografts by
      >30% was associated with an increased type II endoleak rate (11 vs 4.7%) that
      failed to reach statistical significance (P =.27). Aortic neck diameters
      increased significantly by 6 months (P <.001) but then stabilized through 24
      months; the absolute changes at 1 (n = 298), 6 (n = 278), 12 (n = 264), and 24
      months (n = 171) were 0.66 +/- 0.10 mm (3.0%), 1.32 +/- 0.11 mm (5.6%), 1.38 +/-
      0.12 mm (5.9%), and 1.44 +/- 0.16 mm (6.1%), respectively. Linear regression
      analysis demonstrated no correlation between endograft oversizing and aortic neck
      dilation at 12 (P =.86) or 24 months (P =.64). CONCLUSIONS: Device migration and
      endoleaks were very infrequent after treatment with the Zenith AAA Endovascular
      Graft. However, endograft oversizing of >30% was associated with an approximately
      14-fold increase in device migration (>5 mm) at 12 months and with a
      approximately 16-fold increased risk of AAA expansion at 24 months. Although
      further follow-up will be essential to assess whether these early associations
      continue, avoidance of excessive endograft oversizing is recommended.

PMID- 14718808
TI  - Time-resolved magnetic resonance angiography as a noninvasive method to
      characterize endoleaks: initial results compared with conventional angiography.
AB  - PURPOSE: Several types of endoleaks have been described, each with different
      methods of treatment. Conventional arteriography is widely regarded as the gold
      standard for the classification of endoleaks. Recently, faster magnetic resonance
      gradients have allowed for rapid data acquisition and review of vascular studies
      as a real-time continuous angiogram (time resolved magnetic resonance angiography
      [TR-MRA]). This study was performed to compare the findings of TR-MRA with
      conventional angiography for the characterization of endoleaks. METHODS: Between
      June 2002 and June 2003, 12 patients with documented endoleaks following
      endovascular repair of aortic aneurysms (10 abdominal and two thoracic) underwent
      TR-MRA to identify and characterize the endoleak. All patients had nitinol-based
      aortic stent grafts. MRA was performed on a 1.5-Tesla magnet (Sonata class;
      Siemens Medical Systems, Iselin, NJ). The TR-MRA studies were reviewed under
      continuous observation as a "cine MR angiogram." These MRA data sets were used to
      classify the endoleaks into types 1 through 3. The patients underwent
      conventional angiography following the MRA to confirm the findings and to plan
      treatment. The MRA findings were compared with the findings made at conventional
      arteriography. RESULTS: TR-MRA identified seven patients with type 1 leaks,
      including four proximal and three distal. Four patients had type 2 leaks,
      including two arising from the inferior mesenteric artery and two from an
      iliolumbar artery. One patient had a type 3 leak. Conventional angiography
      confirmed the type of endoleak in all 12 patients. CONCLUSION: These initial
      results demonstrate TR-MRA to be an effective noninvasive method for classifying
      endoleaks. This technique may allow for screening of patients with endoleaks to
      identify those requiring urgent repair.

PMID- 14718809
TI  - Multicenter pivotal trial results of the Lifepath System for endovascular aortic
      aneurysm repair.
AB  - PURPOSE: This study was undertaken to assess the results of endovascular aortic
      aneurysm repair with the Lifepath abdominal aortic aneurysm (AAA) graft system.
      METHOD: In a prospective clinical trial, 23 centers used the Lifepath System
      balloon-expandable, modular bifurcated stent graft for elective endovascular
      aortic aneurysm repair. Stent grafts were sized according to computed tomographic
      angiography-based diameter measurements. All repairs were performed in the
      operating room through bilateral surgically exposed femoral arteries. Results
      were assessed with contrast agent-enhanced computed tomography scans and plain
      abdominal x-ray films at 1, 6, 12, 24, 36, and 48 months postoperatively.
      RESULTS: Over 52 months (mean follow-up, 11 months), 227 patients (206 men, 21
      women) were enrolled. Technical implant success rate was 98.7%. There were five
      (2.2%) conversions to open surgery: two emergently because of aortic perforation;
      to treat refractory endoleak, immediate in one and at 12 months in one; and to
      replace a device with wireform fractures that had migrated at 12 months,
      resulting in a proximal endoleak. The perioperative mortality rate was 1.3%.
      There was one operative death during a secondary procedure to repair perforation
      of the aorta. There were two perioperative deaths, from postoperative myocardial
      infarction (n = 1) and pulmonary embolus (n = 1). There were 12 late deaths, from
      coronary artery disease (n = 4), cancer (n = 2), respiratory failure (n = 2),
      sepsis (n = 1), or unknown cause (n = 3). Median length of stay was 2 days (mean,
      4 days). There have been no AAA ruptures after successful implantation of the
      device, no graft limb thromboses, and no limb dislocations. At the time of
      operation endoleak was noted in 43 (19%) patients, but by 6 months this was
      reduced to 8 (5.9%) patients (type I, n = 1; type II, n = 7). There were no type
      III or type IV endoleaks. Secondary interventions to treat endoleaks included
      open conversion (n = 2), placement of extension cuffs (n = 4), repeated balloon
      dilation (n = 3), and coil embolization (n = 6). The two remaining secondary
      interventions were emergent treatment of postoperative bleeding from a groin
      incision, and a colon resection because of postoperative colonic ischemia, for a
      12-month secondary intervention rate of 7.5%. Wireform fractures were noted in
      the first generation Lifepath device in 37 of 79 (47%) patients. Graft migration
      (>10 mm) was observed in five patients (2.2%), each of whom also had two or more
      fractures of the proximal anchoring wireforms. Migration resulted in a proximal
      attachment endoleak in one patient. In response to wireform fractures, the device
      was modified after the initial 79 patients were enrolled. Wireform fracture has
      been observed in six patients since this modification (4%), and in only one
      patient did this involve fracture of a proximal anchoring wireform; none of these
      patients has had endoleak or graft migration. By 12 months, mean aneurysm
      diameter was noted to decrease by 9 mm (P <.0001), and mean aneurysm volume by 42
      mL (P <.0001) from the preoperative visit. CONCLUSION: The Lifepath System
      demonstrates a low endoleak and secondary intervention rate and high sac
      regression rate, compared with other devices. The unique balloon-expandable
      design offers the advantages of precise placement and high radial force. The
      device appears to be highly resistant to limb thrombosis and modular component
      separation. Patients were protected from AAA rupture after successful device
      implantation, and demonstrated significant reduction in AAA diameter and volume.
      Fractures of the wireforms of the main body of the device have been observed.
      Careful long-term follow-up is necessary.

PMID- 14718811
TI  - Focused screening for occult carotid artery disease: patients with known heart
      disease are at high risk.
AB  - OBJECTIVES: Stroke puts a major financial burden on our healthcare system.
      However, carotid duplex scanning performed as a screening test for occult carotid
      artery stenosis (CAS) currently is not reimbursed by Medicare. The goals of this
      study were to develop a cost-effective stroke screening program, to determine the
      prevalence of potential causes of stroke in this population, and to define a
      population at high risk in which screening would be most effective. METHODS: In a
      community-based stroke screening program, patients were eligible if they were
      older than 60 years and had a history of either hypertension, heart disease, or
      cigarette smoking, or a family history of stroke. Screening included blood
      pressure determination, an electrocardiographic rhythm strip, and a previously
      validated modified carotid duplex ultrasound examination to detect CAS 50% or
      greater. The relationships between standard demographic risk factors and
      screening outcomes were analyzed. RESULTS: Screening was performed in 610
      patients. Unilateral or bilateral CAS was detected in 66 patients (10.8%). The
      finding of occult CAS was more prevalent than that of new hypertension (2.6%) or
      new atrial fibrillation (0.5%). Patients with known hypertension were
      significantly more likely to have CAS than were those without hypertension (12.7%
      vs 7.8%; P =.05). Patients with heart disease were significantly more likely to
      have CAS than were those without heart disease (18.2% vs 8%; P <.0001). Patients
      with both risk factors were significantly more likely to have occult carotid
      artery disease than were patients without either risk factor (22.1% vs 8.5%; P
      <.0001). Multivariate analysis with logistic regression revealed a history of
      heart disease as an independent predictor of occult carotid artery disease (odds
      ratio 95% confidence interval, 1.4-4.4). Type of heart disease was not a
      significant factor in predicting occult CAS. Direct cost of the screening,
      including community outreach, nurses, technicians, support staff, and
      miscellaneous expenses, was less than $75 per patient. CONCLUSIONS: In a
      screening program for treatable causes of potential stroke, CAS was the most
      commonly diagnosed disease. More than one of every five patients with known
      hypertension and heart disease had occult CAS. Known heart disease of any type
      was a significant independent predictor of occult CAS. Screening for treatable
      causes of potential stroke can be cost-effective. This information could help to
      further target populations to screen for occult CAS and to justify reimbursement
      for screening carotid duplex scanning examinations.

PMID- 14718813
TI  - Disease progression in contralateral carotid artery is common after
      endarterectomy.
AB  - OBJECTIVE: Although the North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) have helped to
      define the role of carotid endarterectomy (CEA) for both symptomatic and
      asymptomatic lesions, the role of surveillance of the contralateral carotid
      artery remains unclear. The purpose of this study was to determine the
      progression of contralateral carotid artery disease with serial duplex ultrasound
      scans after CEA compared with the recurrent stenosis rate for the carotid artery
      ipsilateral to the CEA. METHODS: From January 1990 to December 2000, 473 CEA
      procedures were performed at a Veterans Affairs Medical Center. From this group
      we identified 279 patients who had undergone first-time CEA, as well as
      preoperative duplex scanning and postoperative duplex scanning at least once, in
      the vascular laboratory. At each visit stenosis of the internal carotid artery
      (ICA) was categorized as none (0%-14%), mild (15%-49%), moderate (50%-79%),
      severe (80%-99%), or occluded. Analysis of probability of freedom from
      progression was determined. Progression was defined as an increase in ICA
      stenosis 50% or greater or increase to a higher category of stenosis if baseline
      was 50% or greater. The Cox proportional hazards model was used for data
      analysis. RESULTS: Mean patient age was 65.7 years (range, 33-100 years). The
      1024 carotid duplex ultrasound scanning examinations performed (mean, 3.7; range,
      2-13) included the last study done before the index CEA and all studies done
      after the CEA. Mean follow-up was 27 months (range, 1-137 months). Forty-six
      patients were found to have contralateral carotid occlusion at initial duplex
      scanning, and were therefore excluded from the contralateral progression
      analysis. Contralateral progression was more frequent than ipsilateral recurrent
      stenosis at long-term follow-up (P <.01). Annual rates of "any progression" and
      "progression to severe stenosis or occlusion" were 8.3% and 4.4%, respectively,
      for contralateral arteries, and 4.3% and 2.4%, respectively for ipsilateral
      arteries. As a result of surveillance, 43 contralateral CEAs (19% of initial
      cohort) were performed. Carotid stenosis regressed in 25 arteries (10.7%).
      Baseline clinical and demographic factors did not predict disease progression.
      Baseline contralateral stenosis did not predict time to "any progression," but
      was a strong predictor of "progression to severe stenosis or occlusion" (P
      <.001). CONCLUSIONS: After CEA, we identified an 8.3% annual rate of progression
      of contralateral carotid artery stenosis and a 4.4% annual rate of progression to
      severe stenosis or occlusion. Baseline contralateral stenosis was significantly
      predictive of progression to severe stenosis or occlusion. Clinical and
      demographic factors were not helpful in predicting which patients would have
      disease progression. These data may help in assessing the cost effectiveness of
      duplex scanning surveillance after CEA.

PMID- 14718815
TI  - Carotid artery stenting: is there a need to revise ultrasound velocity criteria?
AB  - OBJECTIVES: Ultrasound (US) velocity criteria have not been well-established for
      patients undergoing carotid artery stenting (CAS). A potential source of error in
      using US after CAS is that reduced compliance in the stented artery may result in
      elevated velocity relative to the native artery. We measured arterial compliance
      in the stented artery, and developed customized velocity criteria for use early
      after CAS. METHODS: US was performed before and within 3 days after CAS, and
      after 1 month in a subset of 26 patients. Post-procedural peak systolic velocity
      (PSV) and end-diastolic velocity (EDV) of the internal carotid artery (ICA),
      PSV/EDV ratio, and internal carotid artery to common carotid artery ratio
      (ICA/CCA) were recorded. These were compared with degree of in-stent residual
      stenosis determined at carotid angiography performed at the completion of CAS.
      Peterson's elastic modulus (Ep) and compliance (Cp) of the ICA were determined in
      a subgroup of 20 patients at the distal end of the stent and in the same region
      in the native ICA before stenting. RESULTS: Ninety CAS procedures were analyzed.
      Mean (+/-SD) angiographic residual stenosis after CAS was 5.4 +/- 9.1%, whereas
      corresponding PSV by US was 120.4 +/- 32.4 cm/s; EDV, 41.4 +/- 18.6 cm/s; PSV/EDV
      ratio, 3.3 +/- 1.2; and ICA/CCA ratio, 1.6 +/- 0.5. PSV was unchanged at 1 month.
      Post-CAS PSV and ICA/CCA ratio correlated most with degree of stenosis (P <.0001
      for both). Only six patients demonstrated in-stent residual stenosis 20% or
      greater, but the standard US threshold of PSV 130 cm/s or greater (validated for
      >20% ICA stenosis in our laboratory) categorized 38 of 90 patients as having
      stenosis 20% or greater. Receiver operator curve analysis demonstrated that a
      combined threshold of PSV 150 cm/s or greater and ICA/CCA ratio 2.16 or greater
      were optimal for detecting residual stenosis of 20% or greater, with sensitivity
      100%, specificity 98%, positive predictive value 75%, and negative predictive
      value 100%. After placement of a stent, the ICA demonstrated significantly
      increased Ep (1.2 vs 4.4 x 10(3) mm Hg; P =.004) and decreased Cp (9.8 vs 3.2 %mm
      Hg x 10(-2); P =.0004). CONCLUSIONS: Currently accepted US velocity criteria
      validated in our laboratory for nonstented ICAs falsely classified several
      stented ICAs with normal diameter on carotid angiograms as having residual in
      stent stenosis 20% or greater. We propose a new criterion that defines PSV less
      than 150 cm/s, with ICA/CCA ratio less than 2.16, as the best correlate to a
      normal lumen (0%-19% stenosis) in the recently stented ICA. This was associated
      with increased stiffness of the stented ICA (increased Ep, decreased Cp). These
      preliminary results suggest that placement of a stent in the carotid artery
      alters its biomechanical properties, which may cause an increase in US velocity
      measurements in the absence of a technical error or residual stenotic disease.

PMID- 14718817
TI  - Risk for stroke after elective noncarotid vascular surgery.
AB  - INTRODUCTION: Patients undergoing operations to treat peripheral vascular disease
      have systemic atherosclerosis and are at risk for stroke. However, the incidence
      and effect of cerebrovascular events on noncarotid vascular surgical outcomes are
      not well-defined. METHODS: Patients undergoing common operations for vascular
      disease from 1997 to 2000 were examined with data from the Veterans Affairs (VA)
      National Surgery Quality Improvement Project and the VA patient treatment files.
      Operations studied included abdominal aortic aneurysmectomy (n = 2551),
      aortobifemoral bypass (n = 2616), lower extremity bypass (n = 6866), and major
      lower extremity amputation (n = 7442). The incidence of perioperative stroke was
      determined, and logistic regression analysis was used to identify independent
      risk factors for stroke. Logistic and linear regression analyses were used to
      quantify the effect of postoperative stroke on adjusted mortality and length of
      stay. Odds ratio (OR) and 95% confidence interval (CI) were defined. P <.05 was
      considered significant. RESULTS: Stroke was uncommon after noncarotid vascular
      procedures, occurring in only 0.4% to 0.6% of patients. Independent risk factors
      for stroke include preoperative ventilation (OR, 11; 95% CI, 5.0-22.3; P <.001),
      previous stroke or transient ischemic attack (OR, 4.2; 95% CI, 2.7-6.4; P <.001),
      postoperative myocardial infarction (OR, 3.3; 95% CI, 1.3-8.7; P =.009), and need
      to return to the operating room (OR, 2.2; 95% CI, 1.4-3.5; P =.001). Factors that
      did not appear to be associated with stroke risk included procedure type,
      diabetes, renal failure, dialysis dependence, number of transfused units of
      blood, and hypertension. After controlling for other postoperative complications
      and comorbid conditions, postoperative stroke significantly increased the risk
      for perioperative mortality (OR, 6.3; 95% CI, 3.4-11.4; P <.001), with similar
      magnitude as postoperative myocardial infarction (OR, 6.3; 95% CI, 3.9-10.1; P
      <.001). Stroke was also associated with a 48% increase in overall length of stay.
      CONCLUSIONS: Stroke after noncarotid peripheral vascular surgery is uncommon, but
      results in markedly increased mortality and length of stay. Stroke risk is most
      strongly associated with previous stroke history and greater degree of illness.
      Patients with these associated conditions deserve particular attention to
      assessing and medically managing modifiable risk factors.

PMID- 14718819
TI  - Management of infected prosthetic dialysis arteriovenous grafts.
AB  - BACKGROUND: Hemodialysis access is one of the most common vascular procedures
      that is performed by vascular and general surgeons. Prosthetic arteriovenous
      graft (AVG) infections pose potentially life-threatening septic and bleeding
      complications, as well as loss of dialysis access. Strategies employed to
      preserve some grafts, prevent morbidity in those with major infections, and
      maintain access are presented. METHODS: Between July 1, 1995 and August 1, 2002,
      1441 AVG procedures were performed at a single institution. Fifty-one (3.5%)
      prosthetic AVG infections in 45 patients were identified. Twenty-seven graft
      infections occurred at a prior incision for placement or revision of a graft. The
      other 24 infections were located within the body of the graft, and 14 of these
      were documented to be at a recent puncture site for hemodialysis access. The most
      common presentation (47% [24/51]) was an exposed graft or a draining sinus tract.
      Management included total graft excision (TGE) when patients presented with
      sepsis or the entire graft was bathed in pus; subtotal graft excision (SGE), when
      all of the graft was removed except an oversewn small cuff of prosthetic material
      on an underlying patent artery; and partial graft excision (PGE), when only a
      limited infected portion of the graft was removed and a new graft was rerouted
      through adjacent sterile tissue to maintain patency of the original graft.
      RESULTS: None of the 45 patients died or developed hand ischemia. A uniformly
      successful outcome was achieved in all patients who were treated with TGE (13/13:
      8 vein patches, 4 primary closure, 1 arterial ligation) or SGE (15/15). However,
      these treatments necessitated placement of a central venous catheter for
      temporary dialysis access and a new AVG later. All of these 28 wounds healed by
      secondary intention, including all 15 cases in which an oversewn cuff of
      prosthetic material remained. Graft patency and wound healing were achieved in
      74% (17/23) of infections treated with PGE, and placement of a temporary dialysis
      access catheter and new AVG were avoided. The 6 failures of PGE ultimately
      required TGE because of nonhealing wounds, but there were no acute hemorrhagic or
      septic events. CONCLUSIONS: Systemic sepsis caused by prosthetic AVG infections
      mandates TGE. SGE and PGE can be safely employed in selected patients with
      infected prosthetic AVGs. SGE maintains patency of the underlying artery and
      avoids a difficult and time-consuming dissection. PGE offers the advantage of
      minimizing extensive dissection of well-incorporated uninfected graft segments
      and allows continued dialysis access at the incorporated portion of the graft.

PMID- 14718821
TI  - Structured exercise improves calf muscle pump function in chronic venous
      insufficiency: a randomized trial.
AB  - OBJECTIVE: Deterioration of calf muscle pump function is associated with
      progression of chronic venous insufficiency (CVI). We postulated that a
      supervised exercise program would improve calf muscle strength and venous
      hemodynamics in patients with CVI. METHODS: We recruited 31 patients for this
      randomized, prospective trial. Inclusion criteria required the presence of skin
      changes or ulceration (CEAP 4, 5, 6), and duplex ultrasound scanning (reflux or
      scarring) and air plethysmographic (APG) evidence of CVI. Subjects were
      randomized into control (n = 13) and therapy (n = 18) groups. Class II (30-40 mm
      Hg) compression hosiery was given to all. The experimental group received
      physical therapy designed specifically to strengthen calf musculature. Dynamic
      strength and power were measured with a Biodex II dynamometer (Biodex Medical
      Systems, Shirley, NY) at slow and fast speeds. Reflux (venous filling index) and
      calf pump function (ejection fraction, residual volume fraction) were measured
      with APG. Quality-of-life questionnaires and venous severity scores were also
      administered. Outcomes were compared 6 months after initiation of exercise.
      Probability of treatment effect was tested with univariate analysis of variance,
      with control for baseline values. RESULTS: Demographic variables and medical
      comorbidities were not different between groups. After 6 months of intervention,
      indicators of calf pump function returned to a normal range in the therapy
      (experimental) group. Mean residual volume fraction was improved in the exercise
      group (-8.75 +/- 4.6 vs 3.4 +/- 2.9 in the control group; P <.029). Mean ejection
      fraction was increased in the exercise group (3.48 +/- 2.7 vs -1.4 +/- 2.1 in the
      control group; P <.026). Reflux, while substantially greater than the normal
      value of 2.0 mL/s in both groups, was unchanged. The exercise regimen improved
      isokinetic peak torque/body weight at both slow speed (3.1 +/- 1.4 in the therapy
      group vs -1.0 +/- 1.1 in the control group; P <.05) and fast speed (2.8 +/- 0.9
      in the therapy group vs - 0.3 +/- 0.6 in the control group; P <.03). No changes
      were observed in quality-of-life or severity scores. CONCLUSIONS: Calf muscle
      pump function and dynamic calf muscle strength were improved after a 6-month
      program of structured exercise. Directed physical conditioning of the calf
      musculature may prove beneficial for patients with or without alternative
      management options for severe CVI. Further research on exercise for patients with
      CVI is warranted.

PMID- 14718823
TI  - Prospective randomized controlled trial: conventional versus powered phlebectomy.
AB  - OBJECTIVES: Transilluminated powered phlebectomy (TriVex) is a new surgical
      technique that uses tumescent dissection, transillumination, and powered
      phlebectomy. The purpose of this study was to compare TriVex with conventional
      varicose vein surgery in terms of pain, cosmesis, recurrence, complications, and
      operating time. METHODS: One hundred eighty-eight limbs in 141 patients (33 men,
      108 women; mean age, 42.5 years) with varicose veins were randomised to
      conventional (n = 100) or TriVex (n = 88). Exclusion criteria were venous
      ulceration or deep venous disease. Varicosities were graded with CEAP and
      clinical assessment (grades 1-3), and were similar in both groups. Randomization
      was single blinded. Long or short saphenous vein ligation or stripping was
      performed as indicated with duplex scanning. Operative time was from skin
      incision to leg bandaging. Phlebectomy was performed with conventional stab
      avulsions or TriVex. Patients completed assessment forms preoperatively and
      postoperatively (2, 6, 26, 52 weeks), and this was supplemented with physician
      clinical evaluation. Pain was assessed with visual analog score. RESULTS: There
      was a significant difference in the number of incisions for phlebectomy in the
      two groups (conventional, n = 29; TriVex, n = 5; P <.0001). TriVex was faster in
      the grade 3 (extensive) group, but this did not reach statistical significance.
      There was no difference in mean postoperative pain score over 8 days in the two
      groups (P =.4624). At 2 weeks there was no significant difference between the
      groups with regard to bruising (P =.77), cellulitis (P =.33), and numbness (P
      =.33). At 6 weeks there was no significant difference between the groups with
      regard to nerve injury (P =.97), residual veins (P =.79), cosmetic score (P
      =.837), and overall satisfaction (P =.878). At 6 and 12 months, there was no
      significant difference in cosmesis (P =.955, P =.088, respectively) or recurrence
      (P =.27, P =.11, respectively). CONCLUSIONS: TriVex is a safe and effective
      method for excision of varicosities and compares well, after a learning curve,
      with conventional surgery in regard to complications and recurrence. It has the
      advantage of a trend toward reduced operating time in extensive varicosities, and
      significantly fewer incisions, although there was no perceived difference in
      cosmesis during follow-up.

PMID- 14718825
TI  - Variable sac behavior after endovascular repair of abdominal aortic aneurysm:
      analysis of core laboratory data.
AB  - OBJECTIVES: The behavior of the aneurysm sac after endovascular grafting has been
      the subject of significant speculation. The importance of sac behavior is
      manifested by the correlation between aneurysm size or size change and risk for
      rupture, and potentially further extrapolated to define the need for secondary
      intervention. This study was undertaken to define graft-specific differences and
      the effect of endoleak on sac remodeling. METHODS: Core laboratory data were
      obtained for three US Phase II clinical trials. Patients were included if they
      met anatomic inclusion criteria and underwent placement of the latest version of
      a bifurcated endovascular prosthesis. Unsupported Dacron (Ancure), supported
      Dacron (Zenith), and expanded polytetrafluoroethylene (Excluder) grafts were
      evaluated. Digitized images were electronically assessed for aneurysm size (area,
      maximum, minimum diameter) with National Institutes of Health Image software. Two
      blinded reviewers analyzed each radiographic study to ensure accurate image
      selection and establish the presence or absence of endoleak. A third reviewer
      adjudicated discrepancies. chi(2) analysis and mixed nonlinear modeling were used
      to analyze the results. RESULTS: Of 1506 patients evaluated, 723 (227 Ancure, 343
      Excluder, 153 Zenith) met inclusion criteria for the study. Mean follow-up was
      23.2 months (Ancure, 31.3 months; Excluder, 19.6 months; Zenith, 19.3 months).
      The incidence of any endoleak was 39.1% (Ancure, 58.1%; Excluder, 34.7%; Zenith,
      20.9%; P <.001). Type of prosthesis, presence or absence of endoleak, and
      baseline size were determinants of rate of aneurysm shrinkage. Reduction in sac
      size was greatest with the Zenith graft, followed by the Ancure and Excluder
      grafts. Presence of endoleak had a moderating effect on rate of sac shrinkage
      with the Zenith and Ancure grafts; however, sac size increased in the presence of
      endoleak with the Excluder graft. Finally, baseline size was positively
      correlated with rate of aneurysm shrinkage. CONCLUSIONS: The behavior of the
      aneurysm sac depends on the type of prosthesis, presence or absence of endoleak,
      and baseline size of the sac. Differential sac behavior must be considered when
      determining the need for secondary interventions, timing follow-up studies, and
      assessing success or failure of endovascular repair.

PMID- 14718826
TI  - Cumulative sum failure analysis of the learning curve with endovascular abdominal
      aortic aneurysm repair.
AB  - PURPOSE: The purpose of this study was to evaluate the importance of experience
      and the learning curve with endovascular abdominal aortic aneurysm (AAA) repair.
      METHODS: A retrospective analysis was performed of all elective endovascular AAA
      repairs attempted by an individual surgeon and radiologist over a 4-year period.
      The primary outcome variable was achievement and 30-day maintenance of initial
      clinical success as defined by the Society for Vascular Surgery/American
      Association of Vascular Surgery reporting standards. Following standard
      statistical analysis, the cumulative sum (CUSUM) method was used to analyze the
      learning curve, with a predetermined acceptable failure rate of 10% and
      calculated 80% alert and 95% alarm lines. RESULTS: Ninety-six elective
      endovascular AAA repairs were attempted by this team between 1998 and 2002 (mean
      age 74 +/- 0.8 years; mean aneurysm diameter 5.98 +/- 0.8 cm). Initial clinical
      success was achieved and maintained in 85 of 96 patients (88.5%). Although
      results were acceptable throughout the study period, improved results with
      respect to the target failure rate (10%) were not achieved until 60 patients were
      treated. The learning or CUSUM curves did not differ for different device
      manufacturers, with improved results being achieved following 20 implantations of
      each device. The results did differ when comparing aortouniiliac grafts (n = 27)
      and bifurcated grafts (n = 64). Results with bifurcated grafts remained
      consistent throughout the study period, whereas with aortouniiliac grafts,
      results improved after only a few procedures in comparison with the target
      failure rate. CONCLUSION: Success rates with endovascular aneurysm repair will
      improve with an individual's experience. The CUSUM method is a valuable tool in
      the evaluation of this learning curve, which has credentialing and training
      implications. Although acceptable results were obtained throughout the study
      period, this analysis indicates that 60 endovascular aneurysm repairs, or 20 with
      an individual device, are necessary before optimal rates of initial clinical
      success can be achieved. These results can be achieved more readily with
      aortouniiliac grafts than with bifurcated grafts.

PMID- 14718827
TI  - Aneurysm enlargement following endovascular aneurysm repair: AneuRx clinical
      trial.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and
      significance of aneurysm enlargement, with or without treatment, in relation to
      the primary end points of rupture, surgical conversion, aneurysm-related death,
      and survival following endovascular repair. METHOD: Aneurysm (AAA) size changes
      and clinical outcome of all patients treated from 1997 through 1998 during the
      Phase II AneuRx multicenter clinical trial of endovascular AAA repair were
      reviewed. Aneurysm dimensions and the presence or absence of endoleak were
      determined by an independent core laboratory, with enlargement or shrinkage
      defined as a diameter change of 5 mm or more compared with baseline. RESULTS:
      Among 383 patients (89% men, 11% women, age 73 +/- 9 years), with a mean device
      implant time of 36 +/- 11 months (median = 39 months), aneurysm diameter
      decreased from 5.7 +/- 1.0 at baseline to 5.2 +/- 1.0 at 3 years (P =.0001). A
      total of 46 patients (12%) experienced AAA enlargement, 199 patients (52%) had no
      change in AAA diameter, and 138 patients (36%) had a decrease in AAA diameter of
      5 mm or more. Significant risk factors for enlargement included age (enlargement
      patients were 4 years older on average than patients with aneurysms that
      decreased in size; P =.002) and the presence of an endoleak (P <.001). Among
      patients with endoleak at any time, 17% had aneurysm enlargement, whereas only 2%
      of patients without endoleak had aneurysm enlargement (P <.001). Patients with
      enlargement were more likely to undergo secondary endovascular procedures and
      surgical conversions (P <.001). Twenty patients (43%) with enlargement underwent
      treatment, and 26 patients were untreated. There were two deaths following
      elective surgical conversion and one death in a patient with untreated
      enlargement and a type I endoleak. Three aneurysms ruptured: one with
      enlargement, one with no change, and one with a decrease in aneurysm size; all
      three aneurysms were larger than 6.5 cm. Kaplan-Meier analysis showed that
      freedom from rupture at 3 years was 98% with enlargement, 99% with no change, and
      99% with decrease in AAA size (log-rank test, not significant). Freedom from AAA
      death at 3 years was 93% in patients with enlargement, 99% in no increase, and
      99% in decrease (P =.005). Survival at 3 years was 86% with increase, 82% with no
      change, and 93% with decrease (P =.02). CONCLUSIONS: Aneurysm enlargement
      following endovascular repair was not associated with an increased risk of
      aneurysm rupture or decrease in patient survival during a 3-year observation
      period. Aneurysm size rather than enlargement may be a more meaningful predictor
      of rupture. Close follow-up and a high re-intervention rate (43%) may account for
      the low risk of rupture in patients with enlargement. The long-term significance
      of aneurysm enlargement following endovascular repair remains to be determined.

PMID- 14718828
TI  - Is elevated creatinine level a contraindication to endovascular aneurysm repair?
AB  - PURPOSE: It is widely believed that chronic renal insufficiency (CRI) greatly
      increases the risk associated with endovascular abdominal aortic aneurysm repair
      (EVAR) and is a relative contraindication to the procedure and to the use of
      intra-arterial contrast agents (IACA). We reviewed a 5-year EVAR experience to
      determine whether the procedure and use of IACA have an important deleterious
      effect on renal function in patients with and without pre-existing CRI. METHODS:
      Endovascular aneurysm repair (EVAR) was performed in 200 patients with a variety
      of endografts, with intra-arterial contrast agents. The patients were
      retrospectively assigned to three groups on the basis of preoperative serum
      creatinine concentration (Cr): group 1 (n = 108), Cr less than 1.5 mg/dL (normal
      range); group 2 (n = 65), Cr 1.5 to 2.0 mg/dL; group 3 (n = 27), Cr 2.1 to 3.5
      mg/dL. No patients had undergone hemodialysis. In groups 2 and 3, patients
      received hydration perioperatively, and received mannitol intraoperatively; no
      nephrotoxic drugs were administered during the procedure, other than nonionic
      contrast agent (Omnipaque 350). RESULTS: The incidence of postoperative
      complications between the three study groups was not statistically different. In
      group 1 a transient increase in serum Cr (>30% over baseline and >1.4 mg/dL) was
      noted in three patients (2.7%), two of whom (1.9%) required temporary
      hemodialysis and one (0.9%) who died of renal failure. In group 2 a transient
      increase in serum Cr was noted in two patients (3.1%); both patients (3.1%)
      required temporary hemodialysis, and one patient (1.5%) died of renal failure. In
      group 3 a transient increase in serum Cr was noted in two patients (7.4%); one
      patient (3.7%) required temporary hemodialysis, and one patient (3.7%) died of
      renal failure. Perioperative hypotension significantly increased the risk for
      elevated serum Cr and death (P <.05), and larger contrast volume was associated
      with an increase in serum Cr (P <.05) during the postoperative period.
      CONCLUSIONS: EVAR with intra-arterial contrast agents can be accomplished in
      patients with chronic renal insufficiency who do not require dialysis, with
      limited and acceptable morbidity and mortality, similar to that observed with
      open aneurysm repair. Contrary to other reports in which perioperative
      precautions were not used, our study shows that with EVAR the risk for worsening
      renal failure, dialysis, and death is only slightly, and not significantly,
      greater in patients with preoperative chronic renal insufficiency compared with
      patients with normal renal function. Perioperative hypotension and increased
      contrast volume are significant risk factors for postoperative increase in serum
      Cr and death. With appropriate precautions such as averting perioperative
      hypotension and limiting the volume of nonionic contrast agents, elevated Cr need
      not be a contraindication to EVAR with intra-arterial contrast agents.

PMID- 14718829
TI  - Disappointing results with a new commercially available thoracic endograft.
AB  - INTRODUCTION: New devices for endovascular treatment of thoracic aortic diseases
      were recently approved for clinical use by European authorities, obtaining the
      Conformite Europeenne (CE) mark. In all patients who underwent endovascular
      treatment of a thoracic aortic disease in 2002, we used a new CE-marked device,
      the Endofit stent graft. The device is constituted of nitinol stents and
      polytetrafluoroethylene fabric, and has a simple design and delivery system.
      METHODS: During 2002, 11 patients (mean age, 75 years; range, 66-85 years)
      underwent treatment of atherosclerotic aneurysm (n = 9), chronic type B
      dissection (n = 1), and intramural hematoma (n = 1). Disease involved the
      descending thoracic aorta in 7 patients and the distal aortic arch in 4 patients.
      RESULTS: In all cases the Endofit stent grafts were successfully deployed in the
      intended position. No postoperative paraplegia or paraparesis was recorded. There
      were two in-hospital deaths: 1 patient died in the operating room (postmortem
      examination showed a kinked graft); and the other patient died in the intensive
      care unit on postoperative day 30, after an intraoperative stroke. One surgical
      conversion was performed 2 weeks after the procedure, because of total collapse
      of the graft due to rupture of three stents. Other graft-related complications
      included type I endoleak (n = 2), type II endoleak (n = 1), and incomplete
      opening of the device (n = 1). CONCLUSION: Endovascular treatment of thoracic
      disease with the Endofit graft in this small heterogeneous group of patients
      resulted in several complications, which may arise from both the delivery system
      and the graft itself. At present, other commercially available endografts may be
      safer for endovascular treatment of thoracic aortic diseases.

PMID- 14718830
TI  - Kommerell's diverticulum and right-sided aortic arch: a cohort study and review
      of the literature.
AB  - We report four consecutive cases of Kommerell's aneurysm of an aberrant left
      subclavian artery in patients with a right-sided aortic arch and the results of a
      systematic review of the literature. In our cohort of patients, three had an
      aneurysm limited to the origin of the aberrant subclavian artery, causing
      dysphagia and cough, and one had an aneurysm involving also the distal arch and
      the entire descending thoracic aorta, causing compression of the right main-stem
      bronchus. A left subclavian-to-carotid transposition was performed in association
      with the intrathoracic procedure, and a right thoracotomy was used in all
      patients. One of the patients underwent surgery with deep hypothermia and
      circulatory arrest, and the others with the adjunct of a left-heart bypass. The
      repair was accomplished with an interposition graft in two patients and with
      endoaneurysmorrhaphy in the others. The postoperative course was complicated by
      respiratory failure and prolonged ventilation in one patient, and one patient
      died because of severe pulmonary emboli. The survivors are alive and well at a
      follow-up of 1 to 3 years. Only 32 cases of right-sided aortic arch with an
      aneurysm of the aberrant subclavian artery have been reported: 12 were associated
      with aortic dissection, and 2 presented with rupture. Surgical repair was
      accomplished in 29 patients. A number of operative strategies were described:
      right thoracotomy, bilateral thoracotomy, left thoracotomy with sternotomy,
      sternotomy with right thoracotomy, and left thoracotomy. In only 12 cases was the
      subclavian artery reconstructed. We believe that a right thoracotomy provides
      good exposure and avoids the morbidity associated with bilateral thoracotomy or
      sternotomy and thoracotomy. We feel that a left subclavian-to-carotid
      transposition completed before the thoracic approach revascularizes the
      subclavian distribution without increasing the complexity of the intrathoracic
      procedure.

PMID- 14718831
TI  - Renovascular disease: effect of ACE gene deletion polymorphism and endovascular
      revascularization.
AB  - BACKGROUND: Renal artery stenosis (RAS) is associated with high cardiovascular
      mortality and significant clinical complications, including resistant
      hypertension and ischemic nephropathy. Despite availability of endovascular
      revascularization techniques, determining which patients should undergo
      revascularization and the timing of the procedure still are controversial.
      Several studies have reported a higher frequency of the DD genotype of the
      insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE)
      gene in patients with RAS, and one study found higher mortality in patients with
      the DD genotype. Material and methods We retrospectively studied 100 patients
      with documented atherosclerotic RAS and evaluated long-term (median follow-up, 28
      months) mortality, blood pressure control, and renal function in relation to the
      ACE genotype and two therapeutic strategies, that is, endovascular treatment with
      percutaneous renal transluminal angioplasty or stenting (ET group) versus
      conservative drug therapy (CT group). RESULTS: Comparison between therapeutic
      groups showed a higher cumulative probability of survival (86.7% vs 67.1%),
      better blood pressure control (57.4% vs 29%), and slower decline in renal
      function (17.9% vs 48.4%) in the ET group. The DD genotype was strongly
      represented in our study patients (DD, 50%; II, 15.5%; I/D, 34.5%), but bore no
      relation to mortality, blood pressure control, decline in renal function, or rate
      of recurrent stenosis. CONCLUSIONS: Conservative medical treatment of RAS,
      compared with endovascular treatment, is associated with higher mortality, poorer
      blood pressure control, and impaired renal function over the long term. Early
      endovascular treatment enables amelioration of this unfavorable evolution. The DD
      genotype does not predict clinical outcome of RAS.

PMID- 14718832
TI  - Early carotid endarterectomy after acute stroke.
AB  - PURPOSE: Carotid endarterectomy (CEA) after acute stroke is generally delayed 6
      to 8 weeks because of fear of stroke progression. This delay can result in an
      interval stroke rate of 9% to 15%. We analyzed our results with CEA performed
      within 1 to 4 weeks of stroke. METHODS: Records for all patients undergoing CEA
      after stroke between 1980 and 2001 were analyzed. Perioperative evaluation
      included carotid duplex scanning or angiography, and head computed tomography or
      magnetic resonance imaging. All patients with nonworsening neurologic status,
      additional brain territory at risk for recurrent stroke, and severe ipsilateral
      carotid stenosis underwent CEA. Patients were grouped according to time of CEA
      after stroke: group 1, first week; group 2, second week; group 3, third week;
      group 4, fourth week. Statistical analysis was performed with the chi(2) test,
      logistic regression, and analysis of variance. RESULTS: Two hundred twenty-eight
      patients underwent CEA within 1 to 4 weeks of stroke. Perioperative permanent
      neurologic deficits occurred in 2.8% of patients in group 1 (72 procedures), 3.4%
      of patients in group 2 (59 procedures), 3.4% of patients in group 3 (29
      procedures), and 2.6% of patients in group 4 (78 procedures). There was no
      relationship between location or size of preoperative infarct and time of
      surgery. Only preoperative infarct size correlated with probability of neurologic
      deficit after CEA (P <.05). CONCLUSION: Incidence of postoperative stroke
      exacerbation is similar at all intervals. The results are within acceptable
      limits for treatment of symptomatic carotid stenosis. CEA may be performed within
      1 month of stroke with similar results at all intervals during this period.

PMID- 14718833
TI  - Safety and durability of redo carotid operation: an 11-year experience.
AB  - PURPOSE: With the recent emergence of carotid stenting in the management of
      carotid disease, the role of surgery has been challenged, particularly for
      recurrent carotid stenosis. This study was undertaken to determine the safety and
      durability of redo carotid operation (RCO) for recurrent stenosis. METHODS: A
      retrospective review identified 64 consecutive patients who underwent 66 RCOs
      between 1990 and 2000. There were 33 males (52%) and 31 females, with a mean age
      of 68.2 years (range, 38-84 years). The mean interval from the primary carotid
      surgery to RCO was 77.5 months (range, 1-292 months). Operative indications were
      severe asymptomatic stenosis in 33 cases (50%), transient ischemic attacks (TIA)
      or amaurosis fugax in 25 (38%), recent stroke in 6 (9%), and nonhemispheric
      symptoms in 1. Two operations were tertiary carotid reconstructions. A total of
      56 (85%) patch angioplasties were performed, 49 with vein and 6 with synthetic
      material. Primary closure was performed in three cases (5%), whereas
      interposition grafts were required in eight (12%). Complete follow-up was
      available in 59 patients (92%) and averaged 4.3 years (range, 0.2-12.9 years);
      97% of patients underwent follow-up duplex scanning. RESULTS: There were no
      operative deaths and only two operative strokes (3.1%). Permanent cranial nerve
      deficit occurred in one patient (1.5%). Late stroke occurred in five patients:
      four ipsilateral and one contralateral. Kaplan-Meier estimates for 5- and 10-year
      stroke-free survival were 92% and 74%, and for overall survival were 72% and 50%.
      Duplex scanning detected significant recurrent carotid stenosis (>80%) or
      occlusion in six cases (9%) at a mean follow-up of 4.1 years. Kaplan-Meier
      estimates for freedom from recurrent stenosis of >80% were 94% and 86% at 5 and
      10 years. CONCLUSIONS: RCO for recurrent carotid stenosis can be performed safely
      with excellent protection from stroke and long-term durability. These data
      provide a standard against which the results of carotid stenting can be compared.

PMID- 14718834
TI  - Who doesn't receive carotid endarterectomy when appropriate?
AB  - OBJECTIVE: The purpose of this study was to identify clinical and nonclinical
      factors associated with failure to perform carotid endarterectomy (CEA) in
      patients with clinically appropriate indications. We analyzed data from a
      prospective cohort study performed at five Veterans Affairs medical centers.
      Patients were referred for carotid artery evaluation if they had at least 50%
      stenosis in one carotid artery, had no history of CEA, and were independently
      classified preoperatively as appropriate candidates for CEA, according to
      clinical criteria. The primary outcome was receipt of CEA within 6 months of
      evaluation. Data were collected by medical record review and interview regarding
      clinical status, and patient and physician perception of the risks and benefits
      of CEA. RESULTS: Among clinically appropriate candidates for CEA, 66.8% (n = 233)
      did not undergo the operation. Compared with patients who did undergo CEA, a
      greater proportion of these patients had no symptoms (68.7% vs 45.7%; P <.001). A
      twofold greater proportion of patients who did not undergo CEA were in the
      highest quartile of reported aversion to surgery. Moreover, a fourfold greater
      proportion were perceived by their physicians to be at less than 5% risk for
      future stroke without the operation, and more than a twofold greater proportion
      were believed to experience less than 5% efficacy from the operation by their
      providers (P <.01). In multivariable analyses, four characteristics were
      significantly associated with whether an appropriate candidate did not receive
      CEA: asymptomatic disease, less than 70% stenosis, high expressed aversion to
      surgery score, and low (<5%) provider-perceived efficacy of the operation.
      CONCLUSION: Among patients in the Veterans Affairs health care system who are
      clinically appropriate candidates for CEA, those who did not receive the
      operation were less likely to have symptomatic disease or high-grade carotid
      artery stenosis, but were more likely to report high aversion to surgery and to
      have a provider who believed CEA would not be efficacious.

PMID- 14718835
TI  - Preoperative high-frequency duplex scanning of potential pedal target vessels.
AB  - OBJECTIVE: The aim of this prospective study conducted at a tertiary referral
      center was to evaluate the efficacy of high-frequency duplex scanning in the
      preoperative evaluation of potential pedal target vessels. Material and methods
      The study population consisted of thirty-three consecutive diabetics suffering
      critical limb ischemia, with indications of infra-popliteal occlusive disease.
      Duplex ultrasound was performed by an angiologist unaware of any prior imaging
      procedures. The pedal vessels were divided into four segments. The inner diameter
      , the grade of calcification (on a scale from 1-to-3), the maximal systolic
      velocity, and the resistance index ([V.max syst-V min syst]/V max syst), were
      assessed by using a 13-MHz probe, and the pedal target vessel best suited for
      surgery was identified. Results of duplex scanning were compared to (1) the
      results of selective digital subtraction angiography (DSA) and contrast-enhanced
      magnetic resonance angiography (CE-MRA) studies interpreted by two radiologists,
      (2) the site of distal anastomosis predicted by a vascular surgeon according to
      DSA and CE-MRA studies, (3) the definitive site of distal anastomosis, and (4)
      early postoperative results (patency at three months). RESULTS: Duplex scanning
      depicted significantly more pedal vascular segments than selective DSA- (P =.004,
      McNemar test). Agreement in predicting the site of distal anastomosis expressed
      as kappa value as follows: duplex versus DSA/CE-MRA, kappa 0.71;-DSA/CE-MRA
      versus definitive anastomosis, kappa 0.67; -and duplex versus definitive
      anastomosis kappa 0.82. Two patients were excluded from surgery as all three
      imaging modalities failed to demonstrate a pedal target vessel. Two patients had
      exploratory dissection of a pedal vessel (according to CE-MRA findings) that
      turned out to be occluded (as predicted by duplex scanning). In one patient the
      operation had to be terminated due to lack of autologous bypass material. In 31
      patients who underwent pedal artery bypass, the resistance index could not be
      correlated to the run-off as assessed by intra-operative angiography.
      CONCLUSIONS: High-frequency duplex focusing on the vacular-morphology is a
      worthwhile diagnostic tool to evaluate-potential pedal target vessels and
      extremely helpful when contrast-related methods (selective DSA, CE-MRA) do not
      sufficiently depict the pedal vasculature.

PMID- 14718836
TI  - Clinical and social consequences of Buerger disease.
AB  - PURPOSE: This study was undertaken to assess the clinical course of Buerger
      disease and to analyze the social problems that influence quality of life of
      affected patients. PATIENTS AND METHODS: One hundred ten patients with Buerger
      disease (106 men, 4 women; mean age, 40.0 years) for whom complete data since
      onset of disease were available were included in this retrospective study (mean
      follow-up, 10.6 years). Data were obtained by means of direct interview, written
      reports, or telephone. Data for deceased subjects were gathered from their
      families via written report or telephone. Graft patency was evaluated by means of
      ankle pressure measurement; and in all patients with decreased ankle pressure
      arteriography was performed. RESULTS: Seven of 110 study patients (6%) died
      during follow-up. Cumulative survival rate was 84% up to 25 years after the
      initial consultation. Results of bypass operations (n = 46) were not
      satisfactory. Primary graft patency was 41% at 1 year after operation, 32% at 5
      years, and 30% at 10 years. Secondary graft patency was 54% at 1 year of follow
      up, 47% at 5 years, and 39% at 10 years. However, major amputation was necessary
      in only 5 of 35 limbs (14%) with failed grafts. Forty-seven patients (43%)
      underwent 108 amputation procedures, either major amputation (13 patients) or
      minor amputation (34 patients), of an upper or lower limb. No ischemic ulcers
      occurred or recurred in patients older than 60 years. Forty-one patients who
      stopped smoking did not undergo major amputation. Furthermore, of 69 patients who
      continued smoking, 13 patients (19%) underwent major amputation. There was a
      correlation between incidence of continued smoking and limb amputation (P
      =.0070). In addition, 11 of 13 patients who underwent major lower limb amputation
      (85%) lost their job, compared with 9 of 97 patients without major amputation
      (9%). There was an association between limb amputation and job loss (P <.0001).
      All patients who lost their jobs were engaged in manual labor. CONCLUSION: The
      natural course of life and limb is favorable in many patients with Buerger
      disease. Occurrence or recurrence of necrotic lesions usually is arrested in
      patients older than 60 years. To avoid factors that markedly influence quality of
      life, early treatment and strict instruction to prohibit smoking are mandatory.
      Arterial reconstruction shortens the healing process of ischemic ulcers, despite
      poor long-term results. However, bypass surgery to treat intermittent
      claudication should be limited.

PMID- 14718837
TI  - In-stent recurrent stenosis in stents placed in the lower extremity venous
      outflow tract.
AB  - PURPOSE: This study was undertaken to describe development of in-stent recurrent
      stenosis (ISR) in stents placed in the iliocaval outflow tract and to examine
      possible contributing factors. METHOD: After iliocaval balloon angioplasty and
      stent insertion to treat chronic nonmalignant obstruction, single-plane
      transfemoral venography was performed at least once in 324 limbs, twice in 123
      limbs, three times in 40 limbs, and four times in 4 limbs. ISR was measured with
      a caliper, and expressed as percentage diameter reduction of patent lumen on the
      venograms. Left-right limb ratio was 2.3:1; thrombotic-nonthrombotic disease
      ratio, 1.2:1; negative-positive thrombophilia test ratio, 1.6:1; and above-below
      inguinal ligament stent placement ratio, 4.5:1. Median stent length was 9 cm
      (range, 4-35 cm), and median lumen area before and after stenting was 0.41 cm(2)
      (range, 0-1.65 cm(2)) and 1.70 cm(2) (range, 0.65-4.00 cm(2)), respectively.
      Limbs were divided into groups with no ISR, any degree of ISR, greater than 20%
      diameter reduction, and greater than 50% diameter reduction. Cumulative ISR and
      patency rates were analyzed. Possible contributing factors were examined.
      RESULTS: At 42 months, only 23% of limbs demonstrated no ISR. Cumulative rate of
      limbs with greater than 20% diameter reduction was 61%, and of limbs with greater
      than 50% diameter reduction was 15%. Patient gender or sidedness of the treated
      extremity did not affect outcome. At 36 months, limbs with thrombotic disease had
      higher ISR rates than did limbs without thrombotic disease (63% and 41% of limbs
      with >20% narrowing, and 23% and 4% of limbs with >50% narrowing, respectively; P
      <.01). Similarly, higher rates of ISR were found in patients with thrombophilia
      and long stents extending below the inguinal ligament. Primary, assisted primary,
      and secondary patency rates for the entire population at 3 years were 75%, 92%,
      and 93%, respectively. There was a significant increase in ISR in individual
      limbs, but analysis of groups of stents did not unequivocally show progression.
      CONCLUSION: Severe (>50%) ISR of iliofemoral venous stents is uncommon over the
      short term. The three major risk factors appear to be presence of thrombotic
      disease, positive thrombophilia test results, and stent extending below the
      inguinal ligament (long stents). Although stented limbs that eventually became
      occluded during the study demonstrated similar risk factors, no conclusion
      regarding a cause-effect relationship can be drawn from the present data. Whether
      late occlusion is due to acute thrombosis or to gradual development of true
      intimal hyperplasia requires further study.

PMID- 14718839
TI  - Duplex ultrasound scan findings two years after great saphenous vein
      radiofrequency endovenous obliteration.
AB  - OBJECTIVE: To assess the clinical and duplex ultrasound scan findings in the
      groin and thigh 2 years after great saphenous vein (GSV) radiofrequency
      endovenous obliteration (RFO). METHODS: Sixty-three limbs in 56 patients with
      symptomatic varicose veins and GSV incompetence were treated with RFO, usually
      with adjunctive stab-avulsion phlebectomies, and examined at a median follow-up
      of 25 months, by using a color-coded, duplex sonography protocol that mandated
      views in at least two planes of the saphenofemoral junction (SFJ) and its
      tributaries and at three GSV levels in the thigh. RESULTS: The commonest duplex
      finding in the groin was an open, competent, SFJ with a < or =5-cm patent
      terminal GSV segment conducting prograde tributary flow through the SFJ (82%).
      Despite the presence of a total of 104 patent junctional tributaries, SFJ reflux
      was uncommon, affecting only five limbs. GSV truncal occlusion was observed in
      90% of treated GSVs. Limited segmental treatment was successful in three limbs
      with a midthigh reflux source well below competent terminal and subterminal
      valves. Six GSV trunks had partial or no occlusion, but only one refluxed. These
      were anatomical RFO failures (9.5%) but were clinically improved, including the
      refluxing limb. Neovascularity was not identified in any groin. Thigh
      varicosities were observed in 12 limbs, including telangiectasias and isolated
      small tributary branches. New varicosities, linked to refluxing thigh perforators
      (two), or patent SFJ tributaries (three), were present in five limbs. CONCLUSION:
      RFO is the ideological opposite of high ligation without GSV stripping. It leaves
      physiologic tributary flow relatively undisturbed, does not incite groin
      neovascularity, eliminates the GSV as a refluxing conduit in >90% of limbs and
      has a 2-year, postadjunctive phlebectomy varicosity prevalence of 7.9%, with
      symptom score improvement in 95% of limbs with an initial score higher than zero.

PMID- 14718840
TI  - Complement C5a receptor antagonist attenuates multiple organ injury in a model of
      ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) rupture is associated with a systemic
      inflammatory response syndrome, characterized by increased microvascular
      permeability and neutrophil sequestration, leading to multiorgan dysfunction. We
      examined the role of a novel complement factor 5a (C5aR) receptor antagonist, the
      cyclic peptide AcF-(OpdChaWR), in attenuation of pathologic complement activation
      and tissue injury in a model of AAA rupture. METHODS: Anesthetized rats were
      randomized to sham (control) or shock and clamp (s+c) groups. Animals in the s+c
      group underwent 1 hour of hemorrhagic shock (mean arterial blood pressure < or
      =50 mm Hg), followed by 45 minutes of supramesenteric aortic clamping, then 2
      hours of resuscitated reperfusion. Animals in the s+c group were randomized to
      receive an intravenous bolus of C5aR antagonist at 1 mg/kg or saline solution
      control at the end of hemorrhagic shock. Intestinal and pulmonary permeability to
      iodine 125-labeled albumin was measured as an indicator of microvascular
      permeability. Tissue myeloperoxidase activity, proinflammatory cytokine tissue
      necrosis factor-alpha (TNF-alpha) protein and mRNA, and C5aR mRNA levels were
      measured as indicators of neutrophil sequestration and inflammatory signaling,
      respectively. RESULTS: Lung permeability index was significantly increased in the
      s+c group compared with the sham group (4.43 +/- 0.96 vs 1.30 +/- 0.17; P <.01),
      and prevented with treatment with C5aR antagonist (1.74 +/- 0.50; P <.03). Lung
      myeloperoxidase activity was significantly increased in the the s+c group
      compared with the sham group (2.41 +/- 0.34 U/mg vs 1.03 +/- 0.29 U/mg; P <.009),
      and significantly attenuated with treatment with C5aR antagonist (1.11 +/- 0.09
      U/mg; P <.006). Lung TNF-alpha protein levels were significantly elevated in both
      s+c groups, whereas lung TNF-alpha mRNA expression was significantly
      downregulated in both s+c groups compared with the sham group. Intestinal
      permeability index was significantly increased in animals in the s+c groups
      during reperfusion, compared with sham (P <.001), which was attenuated in early
      reperfusion with treatment with C5a receptor antagonist. Data represent mean +/-
      SEM, group comparisons with analysis of variance and post hoc Scheffe test.
      CONCLUSIONS: These results indicate that a potent antagonist of C5a receptor
      protects the rat intestine and lung from neutrophil-associated injury in a model
      of AAA rupture. These data suggest that complement-mediated inflammation can be
      modulated at the C5a receptor level, independent of proinflammatory TNF-alpha
      production, and prevent acute local and remote organ injury.

PMID- 14718841
TI  - Transcranial myogenic motor-evoked potentials after transient spinal cord
      ischemia predicts neurologic outcome in rabbits.
AB  - OBJECTIVE: Myogenic transcranial motor-evoked potentials (tc-MEPs) were applied
      to monitor spinal cord ischemia in the repairs of thoracoabdominal aortic
      aneurysms. We investigated whether tc-MEPs after spinal cord ischemia/reperfusion
      could be used to predict neurologic outcome in leporine model. METHODS: Tc-MEPs
      were measured at 30-second intervals before, during, and after spinal cord
      ischemia (SCI) induced by balloon occlusion of the infrarenal aorta. Twenty
      rabbits were divided into five groups. Four groups (n = 4 animals in each group)
      had transient ischemia induced for 10, 15, 20, or 30 minutes. In fifth group, the
      terminal aorta at the aortic bifurcation was occluded for 30 minutes. All animals
      were evaluated neurologically 48 hours later, and their spinal cords were removed
      for histologic examination. RESULTS: The tc-MEPs in each SCI group rapidly
      disappeared after SCI. After reperfusion, the recovery of tc-MEPs amplitude was
      inversely correlated to duration of SCI. Tc-MEPs amplitude at one hour after
      reperfusion was correlated with both neurologic score and number of neuron cells
      in the spinal cord 48 hours later. Logistic regression analysis demonstrated that
      the neurologic deficits differed significantly between animals with tc-MEPs
      amplitude of less than 75% of the baseline and those with an amplitude of more
      than 75%. CONCLUSIONS: The amplitude of tc-MEPs after ischemia /reperfusion of
      the spinal cord showed a high correlation with durations of SCI, with neurologic
      deficits, and with pathologic findings of the spinal cord. Tc-MEPs, therefore,
      could be used to predict neurologic outcome. In particular, tc-MEPs whose
      amplitude recovered by less than 75% indicated a risk of paraplegia.

PMID- 14718842
TI  - Domain-dependent action of urokinase on smooth muscle cell responses.
AB  - BACKGROUND: Single-chain urokinase-type plasminogen activator (sc-uPA) is one of
      the key serine proteases involved in modulating cellular and extracellular matrix
      responses during tissue remodeling. Sc-uPA is composed of three domains:
      aminoterminal fragment (ATF), kringle domain, and carboxyterminal fragment (CTF).
      sc-uPA is readily cleaved into these three domain fragments in vitro, each of
      which is biologically active; however, their roles in the microenvironment of the
      vessel wall are poorly understood. PURPOSE: The purpose of this study was to
      determine the role of each domain of sc-uPA on vascular smooth muscle cell (SMC)
      proliferation and migration. METHODS: SMCs were cultured in vitro. Assays of DNA
      synthesis, cell proliferation, and migration were performed in response to sc
      uPA, ATF, kringle, and CTF in the presence and absence of the plasmin inhibitors
      epsilon-aminocaproic acid (EACA) and aprotinin, the Galphai inhibitor pertussis
      toxin, and the mitogen-activated protein kinase 1 (the upstream regulator of the
      extracellular-signal regulated kinase [ERK]) inhibitor PD98059. RESULTS: sc-uPA
      produced dose-dependent increases in DNA synthesis and cell proliferation. These
      responses were dependent on the CTF domain and were sensitive to plasmin
      inhibitors, pertussis toxin, and PD98059. Sc-uPA also induced SMC migration,
      which could be elicited by both ATF and kringle. Migration to sc-uPA, ATF, and
      kringle was both pertussis toxin and PD98059 sensitive, but importantly was
      plasmin-independent. CONCLUSION: sc-uPA induces SMC proliferation and migration,
      which are domain-dependent and mediated in part by Galphai-linked, ERK-dependent
      processes, while only the mitogenic response is protease dependent. These
      findings suggest that migration is linked to a G-protein coupled nonprotease
      receptor, while proliferation is associated with a G-protein coupled protease
      receptor.

PMID- 14718843
TI  - Differential effects of Rho-kinase inhibition on artery wall mass and remodeling.
AB  - PURPOSE: Constrictive remodeling and new artery wall mass contribute to lumen
      narrowing in atherosclerosis and following injury. Rho-kinase, an important
      regulator of myosin phosphorylation and cytoskeletal reorganization, is critical
      to smooth muscle cell (SMC) growth and vasoconstriction, but its role in artery
      wall remodeling is poorly defined. We hypothesized that constrictive artery wall
      remodeling is dependent on Rho signaling so that blocking Rho-kinase would
      promote outward artery wall remodeling in response to intimal hyperplasia and
      thus limit lumen narrowing. METHODS: To test this hypothesis, we first studied
      the effects of the Rho-kinase inhibitor fasudil on SMC remodeling of collagen
      matrix in vitro. Mouse aortic SMCs were seeded into three-dimensional collagen
      gels with and without fasudil, and extent of contraction was measured at 24
      hours. We then used the mouse carotid ligation model to study the effects of Rho
      kinase inhibition on remodeling and intimal hyperplasia in vivo. C57B6/J mice
      were randomly assigned to fasudil (100 mg/kg per day) or vehicle and underwent
      unilateral carotid artery ligation or sham ligation. Remodeling and wall mass
      were measured after 28 days. RESULTS: Fasudil blocked SMC contraction of collagen
      gels in a dose-dependent manner. Complete inhibition of collagen gel remodeling
      was achieved between 10 and 30 micromol/L fasudil. In control mice, carotid
      ligation caused significant thickening of the adventitia, media, and intima (P
      <.01) and outward remodeling of the carotid wall. The external elastic lamina
      (EEL) area increased by 14% versus sham (P <.05), but this increase was
      insufficient to prevent lumen narrowing (-42% vs sham, P <.05). Fasudil treatment
      had favorable effects on wall mass, inhibiting neointimal (P =.04), medial (P
      =.03), and adventitial thickening (P =.07) versus controls. Opposite our
      hypothesis, however, fasudil did not enhance outward artery wall remodeling or
      improve lumen caliber. Rather, inhibiting Rho-kinase blocked outward remodeling
      in response to ligation. EEL area was significantly smaller in treated versus
      control animals (P =.04) and slightly smaller versus shams (P = NS). These data
      suggest that Rho activation contributes significantly to both hyperplasia and
      outward remodeling of the injured artery wall. Rho-kinase may prove an important
      target to limit intimal hyperplasia and prevent restenosis when remodeling is
      improved by other means (eg, stents).

PMID- 14718844
TI  - Alpha-tocopherol preserves endothelial cell migration in the presence of cell
      oxidized low-density lipoprotein by inhibiting changes in cell membrane fluidity.
AB  - OBJECTIVE: Endothelial cell (EC) migration is essential for healing areas of
      arterial injury and angioplasty sites. Iron or copper-oxidized low-density
      lipoprotein (oxLDL(Cu)) inhibits EC migration in vitro, but the effect of
      physiologically relevant monocyte/macrophage-oxidized LDL (oxLDL(cell)) is
      unknown. We postulated that oxLDL(cell) would inhibit EC migration and that this
      inhibition would be reversed by antioxidants. METHODS: The effect of oxLDL(Cu)
      and oxLDL(cell) on EC migration was studied by using a razor scrape assay, and
      migration was assessed after 24 hours. In addition, ECs were incubated with
      various antioxidants, including butylated hydroxytoluene (BHT), probucol, or
      alpha-tocopherol, for 1 hour prior to initiation of the scrape assay and
      application of oxLDL. RESULTS: Both oxLDL(Cu) and oxLDL(cell) inhibited
      migration. The antioxidants did not alter the antimigratory activity of
      oxLDL(Cu), but alpha-tocopherol preserved EC migration in the presence of
      oxLDL(cell). The lack of effect of BHT or probucol suggested that the effect of
      alpha-tocopherol resided not in its antioxidant activity but in its membrane
      stabilizing properties. To test this theory, the effect of oxLDL and alpha
      tocopherol on relative cell membrane fluidity was assessed by fluorescence
      recovery after photobleaching. Both oxLDL(Cu) and oxLDL(cell) increased relative
      membrane fluidity. Preincubation with alpha-tocopherol inhibited the increase in
      membrane fluidity of ECs incubated in oxLDL(cell) but not in oxLDL(Cu).
      CONCLUSIONS: These studies show that alpha-tocopherol preserves EC migration in
      oxLDL(cell) and hastens restoration of the endothelial monolayer after injury by
      inhibiting changes in membrane integrity caused by oxLDL. CLINICAL RELEVANCE:
      Recent studies find that vitamin E is not efficacious in the secondary prevention
      of cardiovascular events, perhaps because vitamin E does not efficiently block
      oxidation pathways known to be operative in atherosclerotic arteries. "Non
      antioxidant" properties of vitamin E, however, could be important in the primary
      prevention of atherosclerosis and its complications. Our in vitro studies show
      that alpha-tocopherol can preserve endothelial migration in the presence of cell
      oxidized LDL. This effect might improve the healing of endothelial injuries at
      sites of arterial repair or angioplasties, especially in lipid-laden arterial
      walls.

PMID- 14718845
TI  - Transesophageal echo-guided endovascular exclusion of thoracic aortic mobile
      thrombi.
AB  - Mobile luminal thrombus of the descending thoracic aorta is an unusual finding in
      patients with peripheral embolization. The diagnosis is best made with
      transesophageal echography (TEE). Traditionally, systemic anticoagulation and
      selective surgical thrombectomy are standard treatment. We present a case report
      of recurrent mobile thrombus despite surgical thrombectomy and systemic
      anticoagulation. We treated it with endovascular exclusion of a descending
      thoracic aorta emboligenic lesion with an endoluminal stent graft, using
      simultaneous TEE and fluoroscopic intraoperative guidance. The patient remains
      symptom-free 9 months after stent-graft implantation. TEE-guided endoluminal
      exclusion should be considered in treatment of descending thoracic aorta
      emboligenic lesions.

PMID- 14718846
TI  - Complications of cerebrospinal fluid drainage in thoracoabdominal aortic aneurysm
      repair.
AB  - Spinal cord ischemia resulting in postoperative paraplegia is a devastating
      complication of thoracoabdominal aortic aneurysm repair, and has been attributed
      to many causes. To prevent spinal cord compartment syndrome, cerebrospinal fluid
      drainage has been used as an adjunct to thoracoabdominal aortic aneurysm repair,
      with procedure-related complications generally occurring infrequently. We present
      two case reports of serious complications from CSF drainage.

PMID- 14718847
TI  - Coexistence of cystic medial necrosis and segmental arterial mediolysis in a
      patient with aneurysms of the abdominal aorta and the iliac artery.
AB  - Segmental arterial mediolysis is an unusual arterial lesion for which
      pathogenesis has remained controversial. We report on a 47-year-old Japanese
      woman who underwent surgery for an abdominal aortic aneurysm that was 10.5 cm in
      diameter and contiguous with a left common iliac aneurysm that was 2.3 cm in
      diameter; the aneurysms were considered to have progressed rapidly in size.
      Pathologic examinations of the respective aneurysms showed cystic medial necrosis
      in the aortic and segmental arterial mediolysis in the iliac aneurysm.
      Coexistence of these two pathologic findings indicates that there may be a strong
      relation between these two disease entities.

PMID- 14718848
TI  - Rupture of internal iliac artery aneurysm presenting as rectus sheath hematoma:
      case report.
AB  - This report describes a ruptured internal iliac artery aneurysm that presented as
      a rectus sheath hematoma (RSH). The patient developed abdominal pain and a large,
      tense lower abdominal wall mass without peritoneal signs. Computed tomography
      scan demonstrated a massive RSH contiguous with a ruptured left internal iliac
      artery aneurysm. Hypovolemic shock prompted immediate laparotomy,
      aneurysmorrhaphy of the ruptured aneurysm, and evacuation of the rectus hematoma.
      This uncommon presentation of internal iliac aneurysm rupture should caution
      against a simple diagnosis of "spontaneous" RSH in a patient with a potentially
      ruptured iliac aneurysm.

PMID- 14718849
TI  - Multiple aneurysms in childhood.
AB  - Arterial aneurysms in children are rare. When present, they are often associated
      with connective tissue disorders or arteritidies. Idiopathic aneurysms occurring
      at multiple sites throughout the arterial tree are rare, with only ten cases
      reported. This report describes a case of multiple arterial aneurysms of
      uncertain origin involving upper-extremity, extracranial cerebrovascular,
      aortoiliac, and renal arteries in a 14-year-old boy. The clinical presentation,
      vascular reconstruction, pathologic findings, and a brief review of the
      literature are described.

PMID- 14718850
TI  - Accessory thyroid gland at carotid bifurcation presenting as a carotid body
      tumor: case report and review of the literature.
AB  - Patients with carotid body tumors referred to vascular surgeons usually undergo
      magnetic resonance imaging (MRI) as part of the workup. We present a case report
      of a 39-year-old woman with a presumed carotid body tumor, as was expected from
      clinical and MRI findings. At surgery, the ectopic thyroid tissue was suspected,
      and resection was performed. Histologic examination showed normal thyroid tissue
      with no sign of malignancy. Postoperative thyroid analysis showed a normally
      located, properly functioning thyroid gland. Ectopic thyroid glands are generally
      found in the midline, as a result of abnormal median migration. Their presence
      lateral to the midline with a proper functioning thyroid gland in its normal
      position is extremely rare. Although several submandibular thyroid glands have
      been reported, a close relation with the carotid arteries was described only
      once. When MRI scans of a presumed carotid body tumor show tumor characteristics
      that are not fully specific for a carotid body tumor, the possibility of ectopic
      thyroid tissue should be entertained, which can be the patient's only properly
      functioning thyroid tissue. In such cases, additional assessment, including
      thyroid tests, should be considered before surgery.

PMID- 14718851
TI  - Necrotizing fasciitis after ambulatory phlebectomy performed with use of
      tumescent anesthesia.
AB  - The high cost of treatment of varicose veins has an important role in public
      health care. The search for a less expensive and office-based procedure led to
      introduction of tumescent local anesthesia for use in ambulatory phlebectomy.
      Although the overall infection rate is low, severe infection has been reported
      after liposuction with tumescent anesthesia. We report necrotizing fasciitis, an
      infection with a mortality rate of 30% to 50%, after ambulatory phlebectomy and
      stripping of the long saphenous vein with use of tumescent anesthesia.

PMID- 14718852
TI  - Aortocaval fistula.

PMID- 14718853
TI  - Screening for abdominal aortic aneurysm: a consensus statement.

PMID- 14718854
TI  - Clinical disagreements between residents and faculty surgeons.

PMID- 14718873
TI  - What's ailing us? Prevalence and type of long-term disabilities among an insured
      cohort of orthodontists.
AB  - Occupational health risks are present in every profession. This article reviews 4
      commonly mentioned conditions that might be health risks in orthodontics and
      dentistry--musculoskeletal problems, carpal tunnel syndrome, dermatoses and
      allergies, and psychosocial problems--and compares the reported prevalence rates
      with data from the American Association of Orthodontists Long-Term Disability
      Insurance Plan. There is an estimated 3.56% prevalence of long-term disability
      among orthodontists. The expected and actual specific conditions affecting
      orthodontists could differ from those of the general public or of general
      dentists and do not appear to equate with self-reported surveys. Suggestions for
      improved reporting are made. Orthodontists appear to be quite healthy compared
      with other insured populations and the general public. Most long-term
      disabilities among orthodontists appear to be chronic illnesses and not
      repetitive injuries or specific occupational hazards.

PMID- 14718874
TI  - Efficiency of a pendulum appliance for molar distalization related to second and
      third molar eruption stage.
AB  - A modified pendulum appliance, including a distal screw and special preactivated
      pendulum springs (built-in straightening activation and toe-in bending), was used
      for bilateral maxillary molar distalization in 36 adolescent patients in various
      stages of the molar dentition. The patients were divided into 3 groups (PG 1-3)
      according to the stage of eruption of their second and third molars. In PG 1 (18
      patients), eruption of the second molars had either not yet taken place or was
      not complete. In PG 2 (15 patients), the second molars had already developed as
      far as the occlusal plane, with the third molars at the budding stage. In PG 3 (3
      patients), germectomy of the wisdom teeth had been carried out, and the first and
      second molars on both sides had completely erupted. Analysis of cephalograms to
      identify any changes in the sagittal plane showed that, in the direction of
      distalization, a tooth bud acts on the mesial neighboring tooth like a fulcrum,
      and that tipping of the first molars in patients in whom the second molar was
      still at the budding stage was thus greater. In patients whose second molars had
      erupted completely, the degree of tipping was greater again when a third molar
      bud was located in the direction of movement. After previously completed
      germectomy of the wisdom teeth, almost exclusively bodily distalization of both
      molars is possible, even without bands being applied to the second molars.
      However, if the first and second molars are distalized simultaneously with a
      pendulum appliance, the duration of therapy will be longer, greater forces will
      have to be applied, and more anchorage will be lost. Statistical analysis of the
      results of dental-angular measurements showed significant differences in the
      degree of molar tipping and reciprocal incisor protrusion. The degree of distal
      tipping of first molars was less in patients with erupted second molars (PG 2 and
      PG 3) than in those whose second molars were not yet erupted (PG 1). For
      instance, the measured angles were 0.9 degrees +/- 3.43 degrees (to the palatal
      plane) and 0.8 degrees +/- 3.4 degrees (to the anterior cranium floor) in PG 2,
      and -0.33 degrees +/- 0.58 degrees and 0.67 degrees +/- 2.08 degrees,
      respectively, in PG 3, contrasting with respective values of 5.89 degrees +/-
      3.74 degrees and 5.36 degrees +/- 3.49 degrees in PG 1. Tipping of erupted second
      molars was much more marked in PG 2 (7.92 degrees +/- 5.83 degrees to the palatal
      plane and 7.55 degrees +/- 5.28 degrees to the anterior cranium floor), but much
      less pronounced in PG 3 (2 degrees +/- 1.73 degrees to the palatal plane and 2
      degrees +/- 2 degrees to the anterior cranium floor) than the corresponding
      movement of the second budding-stage molars in PG 1 (4.06 degrees +/- 2.15
      degrees and 3.97 degrees +/- 2.27 degrees, respectively). The degree of incisor
      protrusion occurring reciprocally with molar distalization was much less in these
      patients (measured angles of 3.28 degrees +/- 1.97 degrees and 2.89 degrees +/-
      2.17 degrees to the palatal plane and anterior cranium floor, respectively) than
      in the patients presenting different stages of the dentition (angles of 5.5
      degrees +/- 3.33 degrees and 6.03 degrees +/- 4.29 degrees, respectively, in PG
      2, and angles of 5.5 degrees +/- 3.28 degrees and 6.67 degrees +/- 3.09 degrees,
      respectively, in PG 3). Moreover, measurement of dental casts in the horizontal
      plane showed not only the targeted mesiobuccal rotation of both maxillary molars,
      but also a vestibular drift of the unbanded second molars.

PMID- 14718875
TI  - Characterization and cytotoxicity of ions released from stainless steel and
      nickel-titanium orthodontic alloys.
AB  - The purpose of this study was to qualitatively and quantitatively characterize
      the substances released from orthodontic brackets and nickel-titanium wires and
      to comparatively assess the cytotoxicity of the ions released from these
      orthodontic alloys. Two full sets of stainless steel brackets of 20 brackets each
      (weight 2.1 g) and 2 groups of 0.018 x 0.025 Ni-Ti archwires of 10 wires each
      (weight 2.0 g) were immersed in 0.9% saline solution for a month. The immersion
      media were analyzed with inductively coupled plasma-atomic emission spectroscopy
      (ICP-AES), and the ionic content was statistically analyzed with 1-way analysis
      of variance (ANOVA). Human periodontal ligament fibroblasts and gingival
      fibroblasts were exposed to various concentrations of the 2 immersion media;
      nickel chloride was used as a positive control for comparison purposes. The
      cytotoxic or cytostatic activity of the media was investigated with the MTT and
      the DNA synthesis assays. The results of the cytotoxicity assay were analyzed
      with 2-way ANOVA and the Tukey test with solution and concentration variants as
      discriminating variables (alpha=0.05). The results indicated no ionic release for
      the nickel-titanium alloy aging solution, whereas measurable nickel and traces of
      chromium were found in the stainless steel bracket-aging medium. Concentrations
      of the nickel chloride solution greater then 2 mM were found to reduce by more
      than 50% the viability and DNA synthesis of fibroblasts; however, neither
      orthodontic materials-derived media had any effect on the survival and DNA
      synthesis of either cells.

PMID- 14718876
TI  - Clinical trial comparing plasma arc and conventional halogen curing lights for
      orthodontic bonding.
AB  - The purpose of this clinical trial was to evaluate the reliability and time saved
      with a plasma arc curing unit (Apollo 95E, Dental/Medical Diagnostic Systems,
      Woodland Hills, Calif) compared with a conventional curing unit (Ortholux XL
      3000, 3M Unitek, St Paul, Minn) for direct bracket bonding with resin adhesive.
      Forty-five patients were involved in the study, and 608 brackets were bonded in a
      contralateral quadrant pattern. The patients were followed for a mean (+/-
      standard deviation) period of 11 +/- 3.2 months. Survival analysis was carried
      out to compare the failure rate for the 2 techniques. The time required for
      bonding with each technique was also recorded. The mean survival time was 399
      days, and there were no significant differences in survival time between the 2
      bonding methods. Twelve bonding failures were reported with each technique. The
      curing time per bracket was significantly reduced with the plasma curing light
      compared with a conventional curing unit (65 +/- 19 vs 82 +/- 31 seconds). The
      plasma arc curing light can save chair-time without affecting the bonding failure
      rate.

PMID- 14718877
TI  - In vivo effect of a resin-modified glass ionomer cement on enamel
      demineralization around orthodontic brackets.
AB  - Because the risk of dental caries increases with the use of orthodontic
      appliances and its control cannot depend only on the patient's self-care, this
      study evaluated the effect of a glass ionomer cement on reducing enamel
      demineralization around orthodontic brackets. Fourteen orthodontic patients were
      randomly divided into 2 groups of 7; they received 23 brackets fitted to their
      premolars, bonded with either Concise (3M Dental Products, St Paul, Minn), a
      composite resin (control group), or Fuji Ortho LC (GC America, Chicago, Ill), a
      resin-modified glass ionomer cement (experimental group). The volunteers lived in
      a city that has fluoridated water, but they did not use fluoridated dentifrices
      during the study. After 30 days, the teeth were extracted and longitudinally
      sectioned; in the enamel around the brackets, demineralization was assessed by
      cross-sectional microhardness. The determinations were made at the bracket edge
      cementing limits, and at occlusal and cervical points 100 and 200 microm away
      from them. In all of these positions, indentations were made at depths from 10 to
      90 microm from enamel surface. Analysis of variance showed statistically
      significant effects for position, material, depth, and their interactions
      (P<.05). The Tukey test showed that the glass ionomer cement was statistically
      more efficient than the control, reducing enamel demineralization in all analyses
      (P<.05). The use of glass ionomer cement for bonding can be encouraged because it
      decreases the development of caries around orthodontic brackets.

PMID- 14718878
TI  - Effect of alloy type and surface conditioning on roughness and bond strength of
      metal brackets.
AB  - The effect of 5 different surface conditioning methods on bonding of metal
      brackets to cast dental alloys was examined. The surface conditioning methods
      were fine (30-microm) or rough (125-microm) diamond bur, sandblasting (50-microm
      or 110-microm aluminum oxide [Al2O3]), and silica coating (30-microm silica).
      Fifty disc-shaped specimens of 5 different alloys (gold-silver, palladium-silver,
      nickel-chromium, cobalt-chromium, and titanium) were ground with 1200-grit
      silicone carbide abrasive and polished before being reused for each conditioning
      method. Polished surfaces were used as negative controls. After measuring surface
      roughness (RZ), metal brackets were bonded to the conditioned alloys with a self
      curing resin composite. Specimens were thermocycled (5000 times, 5 degrees-55
      degrees C, 30 seconds), and shear bond tests were performed. Significantly higher
      (P<.001) surface roughnesses were observed with use of the rough diamond bur (RZ
      approximately 33 microm), 110-microm Al2O3 (RZ approximately 14 microm), and fine
      diamond bur (RZ approximately 10 microm), compared with the controls (RZ
      approximately 1 microm). Silica coating (RZ approximately 4 microm) and 50-microm
      Al2O3 (RZ approximately 4 microm) demonstrated no significant difference (P>.001)
      in roughness when compared with the controls. The control group showed no
      resistance to shear forces (0 MPa). Bond values were greater (19 MPa) when silica
      coating was used, compared with 50-microm Al2O3 (7 MPa) and 110-microm Al2O3 (8
      MPa) for all alloys tested. However, interaction between alloys and conditioning
      methods exhibited significant differences (P<.0001).

PMID- 14718879
TI  - Effect of impression technique on bond strength.
AB  - If the effects of surface preparation (eg, acid etching, laser preparation,
      crystal growth) are to be investigated on the same tooth from which the bond
      strength is recorded, a method of surface replication is required that does not
      affect the subsequent bond. This study investigated the effect of 2 different
      methods of taking impressions on bond strength. Three groups of 11 mandibular
      incisors were used. The labial enamel was etched with 37% phosphoric acid for 30
      seconds. Group A (control) had no impression taken; in group B (silicone),
      impressions were taken with silicone impression material before bonding; in group
      C (polyether), an impression was taken with polyether before bonding. After the
      impressions were taken, GAC brackets (A Company, San Diego, Calif) were bonded to
      the labial surfaces of the etched enamel with Transbond XT light-cured composite
      (3M Unitek, Monrovia, Calif). Teeth with bonded brackets were stored in water at
      37 degrees C for 24 hours, and then bond strength was measured on a testing
      machine. The adhesive remnant index (ARI) was also recorded. The lowest bond
      strength was found after silicone replication (mean [standard deviation]: 8.6
      [1.7] MPa) and the highest in the control group (21.2 [4.0] MPa). There was no
      significant difference between the control group and the polyether replication
      group (19.1 [4.7] MPa). The surface detail replications of polyether and silicone
      were found to be identical. It was concluded that polyether had no significant
      effect on bond strength and was suitable for surface replication before bonding.
      Polyether allows replication of the enamel surface without a significant effect
      on bond strength, and this technique could be used to examine the relationship
      between enamel preparation techniques and subsequent bond strength between
      composite and enamel.

PMID- 14718880
TI  - In vitro evaluation of frictional forces between archwires and ceramic brackets.
AB  - The aim of this study was to evaluate the frictional force between orthodontic
      brackets and archwires. The differences in magnitude of the frictional forces
      generated by ceramic brackets, ceramic brackets with metal reinforced slot, and
      stainless steel brackets in combination with stainless steel, nickel-titanium,
      and beta-titanium orthodontic archwires were investigated. Brackets and wire were
      tested with tip angulations of 0 degrees and 10 degrees. Friction testing was
      done with the Emic DL 10000 testing machine (Sao Jose do Rio Preto, PR, Brazil),
      and the wires were pulled from the slot brackets with a speed of 0.5 cm/min for 2
      minutes. The ligation force between the bracket and the wire was 200 g. According
      to the data obtained, the brackets had frictional force values that were
      statistically significant in this progressive order: stainless steel bracket,
      ceramic bracket with a metal reinforced slot, and traditional ceramic bracket
      with a ceramic slot. The beta-titanium wire showed the highest statistically
      significant frictional force value, followed by the nickel-titanium and the
      stainless steel archwires, in decreasing order. The frictional force values were
      directly proportional to the angulation increase between the bracket and the
      wire.

PMID- 14718881
TI  - Bond strength of various bracket base designs.
AB  - To determine the influence of various bracket base designs on bond strength and
      debond interface, 6 types of metal interlock brackets of different sizes and with
      different base designs were evaluated. The bracket base types and mesh sizes
      tested were as follows: retention groove base (Dynalock, Unitek, Monrovia,
      Calif), circular concave base (Accuarch appliance Formula-R, Tomy, Tokyo, Japan),
      double mesh with 5.1 x 10(-2) mm2 mesh size (Ultratrimm, Dentaurum, Ispringen,
      Germany), double mesh, 3.1 x 10(-2) mm2 (Minidiagonali Roth, Leone, Florence,
      Italy), double mesh, 3.1 x 10(-2) mm2 (Tip-edge Rx-I, TP Orthodontics, LaPorte
      Ind), and double mesh, 2.9 x 10(-2) mm2 (Mini Diamond, Ormco, Glendora, Calif).
      The Unitek bracket is cast in 1 piece; the other brackets are welded together.
      Brackets were bonded to human teeth and then debonded on a testing machine. The
      debond interface was recorded and analyzed with scanning electron microscopy and
      energy-dispersive x-ray spectrometry, and the distribution of interfaces was
      determined. The ranking of bond strength of individual bases (kg/base) from
      highest to lowest was Tomy, Dentaurum, Unitek, Leone, TP Orthodontics, and Ormco.
      The ranking of bonding strength per area squared MPa from highest to lowest was
      Tomy, Dentaurum, Leone, Unitek, TP Orthodontics, and Ormco. Debond in interfaces
      occurred between the bracket and resin, within the resin, or between the resin
      and enamel. The most debonded interfaces were between the bracket and resin and
      between the resin and enamel. The Tomy bracket, with its circular concave base,
      produced greater bond strength than did the mesh-based brackets; among the mesh
      based brackets, Dentaurum, with the larger mesh size, produced greater bond
      strength than the brackets with smaller mesh sizes. The Unitek bracket, with its
      1-piece cast base with retention grooves, ranked in the midrange of bond
      strength.

PMID- 14718882
TI  - Optimum force magnitude for orthodontic tooth movement: a mathematic model.
AB  - The aim of this study was to develop a mathematic model to describe the
      relationship between magnitude of applied force and rate of orthodontic tooth
      movement. Initially, data were extracted from experimental studies in dogs
      (beagles), in which controlled, standardized forces were used to move mandibular
      second premolars distally. Curve-fitting by nonlinear regression analysis
      provided an equation describing the relationship between force magnitude and rate
      of tooth movement in beagles. A similar equation was subsequently used to analyze
      the limited available data from the literature on human canine retraction. The
      maximum rates of tooth movement in humans and dogs are very similar. A threshold
      for force magnitude that would switch on tooth movement could not be defined. The
      model showed that a wide range of forces can be identified, all of which lead to
      a maximum rate of tooth movement.

PMID- 14718883
TI  - Long-term stability of anterior open bite extraction treatment in the permanent
      dentition.
AB  - The purpose of this study was to cephalometrically evaluate the long-term
      stability of anterior open bite extraction treatment in the permanent dentition
      after a mean period of 8.35 years. Cephalometric headfilms were obtained at
      pretreatment, posttreatment, and postretention stages from 31 patients who had
      undergone orthodontic treatment with fixed appliances. Two control groups were
      used. The first, with an age similar to that of the experimental group before
      treatment, was used only to characterize it. The second, with normal occlusion,
      was followed longitudinally for a period comparable with the posttreatment period
      and was used to compare changes during this period. The differences between the
      observation stages in the experimental group were analyzed with paired t tests,
      and the posttreatment changes were compared with the changes of the second
      control group with independent t tests. There was no statistically significant
      decrease of the obtained anterior overbite at the end of the posttreatment
      period. The primary factors that contributed to the nonsignificant decrease of
      the overbite were the normal vertical development of the maxillary and mandibular
      incisors, the smaller vertical development of the mandibular molars, and the
      consequent smaller increase in lower anterior face height, as compared with the
      control group in the long-term posttreatment period. Additionally, 74.2% of the
      sample had a "clinically stable" open bite correction.

PMID- 14718884
TI  - Aspartate aminotransferase activity in pulp of orthodontically treated teeth.
AB  - This study examines the aspartate aminotransferase activity in the pulp of
      orthodontically treated teeth. Seventeen healthy male and female subjects (ages:
      14.5-19.6; mean 16.8 +/- 1.6 years) who needed extraction of the maxillary first
      premolars for orthodontic reasons were enrolled in the study. One randomly chosen
      maxillary first premolar, included in a straight-wire fixed orthodontic appliance
      and supporting orthodontic force, was considered as the test tooth. The
      contralateral first premolar, included in the orthodontic appliance but not
      subjected to mechanical stress, was used as the control tooth. After a week of
      treatment, the dental pulp tissues were extracted from both experimental teeth.
      Aspartate aminotransferase activity was significantly elevated in the test teeth
      as compared with the control teeth. These results demonstrate that in the early
      phases of treatment, orthodontic force application to the teeth can lead to
      significant metabolic changes in the pulp of these teeth.

PMID- 14718885
TI  - Histologic analysis of pulpal revascularization of autotransplanted immature
      teeth after removal of the original pulp tissue.
AB  - The survival rate of replanted and autotransplanted teeth is mainly affected by
      the reaction of the pulp. Pulpal necrosis can cause periapical inflammation and
      inflammatory root resorption. The purpose of this study is to learn more about
      the pulpal changes in autotransplanted immature teeth whose pulp tissue was
      removed before transplantation. The experimental material consisted of 16 single
      rooted teeth with open apices, from a beagle dog (3 months of age). At day 0, 4
      teeth were extracted, the pulpal tissues were removed, and the teeth were then
      transplanted to their contralateral side. The same procedure was carried out on
      days 9, 16, and 23, each time for 4 single-rooted teeth. Longitudinal paraffin
      sections were made for histologic investigation. The results showed that, after 7
      days, 2 of the 4 teeth had an ingrowth of new tissue over one fourth of their
      length. After 14 days, all 4 teeth had ingrowth (> or =one fourth of the pulp
      chamber). At the 21-day observation, more than half of the pulp chambers of all
      teeth were filled, and, after 30 days, there was total ingrowth in 3 of the 4
      teeth. This new tissue consisted of well-organized and well-vascularized
      connective tissue.

PMID- 14718886
TI  - Bone regeneration by bodily tooth movement: dental computed tomography
      examination of a patient.
AB  - A 32-year-old man was examined with computed tomography before and after
      orthodontic treatment, and alveolar bone levels at the edentulous spaces were
      assessed. When the computed tomography scans were compared, 2.2 to 5.2 mm of
      additional craniocaudal alveolar bone remodeling by bodily tooth movement was
      found in the space-opening region. Bodily movement was achieved with single- and
      crossed-lever-arm mechanics. Root resorption measuring 1 to 4 mm was observed at
      the mandibular anterior region, where teeth were used for anchorage to upright
      the molars.

PMID- 14718887
TI  - Nonextraction treatment of a Class II malocclusion and impacted maxillary central
      incisor.
AB  - The multidisciplinary treatment of a patient with a Class II malocclusion and an
      impacted maxillary central incisor is presented. Nonextraction correction of the
      distoclusion was achieved through mandibular growth and protraction of the
      mandibular first molars. Closed-eruption surgical exposure of the incisor,
      combined with soft-tissue revision posteruption, resulted in significantly
      improved facial esthetics.

PMID- 14718888
TI  - What features should I look for in a scanner?

PMID- 14718889
TI  - At what resolution should I scan cephalometric radiographs?

PMID- 14718890
TI  - Litigation, legislation, and ethics. The scope of employment.

PMID- 14718891
TI  - Nerve injuries and varicose vein surgery.

PMID- 14718892
TI  - Quality of life endovascular and open AAA repair. Results of a randomised trial.
AB  - AIM: To compare the quality of life (QoL) in the first postoperative year after
      elective endovascular abdominal aortic aneurysm repair (EVAR) and open repair
      (OR) in a randomised study. METHODS: In the Dutch Randomised Endovascular
      Aneurysm Management (DREAM) trial, patients are randomly allocated to EVAR or OR.
      QoL questionnaires (SF-36 and EuroQoL-5D) were sent to all patients
      preoperatively (PREOP) and at five time points in the first postoperative year
      (3W, 6W, 3M, 6M and 12M). Between November 1999 and August 2002, 153 patients
      (141 male; 12 female) were randomised (78 EVAR and 75 OR; one crossover from OR
      to EVAR). The EuroQoL-5D scores and the eight domains of the SF-36 for the two
      groups were compared using the Mann-Whitney test. Changes over time were analysed
      using the Wilcoxon sign test. RESULTS: There were no statistically significant
      differences in baseline characteristics (age, gender and SVS risk factors). The
      preoperative QoL scores of the study group were similar to the QoL scores of the
      general population of the same age. After 3W the OR group showed a significant
      decrease on the EuroQol-5D (p=0.022) and in six of the eight SF-36 domains. The
      EVAR group also showed a significant decrease on the EuroQol-5D (p=0.004) and in
      5 of the 8 domains of the SF-36. At 6W the EuroQol-5D had recovered to baseline
      in the OR group and the decreased domains of the SF-36 had partially recovered.
      In the EVAR group the EuroQol-5D and three of the five decreased SF-36 domains,
      had returned to baseline. From 6M on, the OR group reported a significantly
      higher score on the EuroQoL-5D than the EVAR group (p=0.045 (6M) and p=0.001
      (12M)). CONCLUSION: In the early postoperative period there is a small, yet
      significant QoL advantage for EVAR compared to OR. At 6 months and beyond,
      patients reported better QoL after OR than after EVAR.

PMID- 14718893
TI  - Is a type II endoleak after EVAR a harbinger of risk? Causes and outcome of open
      conversion and aneurysm rupture during follow-up.
AB  - OBJECTIVE: There is still debate whether type II endoleaks represent a risk for
      the patient after EVAR. Treatment policies vary from fairly conservative to
      active intervention. In this analysis risk factors for type II endoleak and
      adverse events during follow-up were assessed. In addition, risk factors and
      causes for conversion to open repair and for rupture post-EVAR were studied.
      METHODS: The data of 3595 patients, who underwent operation between 1996 and 2002
      in 114 European institutions that collaborated in the EUROSTAR Registry, were
      assessed. To accurately assess the influence of type II endoleaks patients with
      type I, III and combined endoleaks were excluded from the present study cohort.
      RESULTS: A combined adverse outcome event consisting of aneurysmal growth,
      transfemoral reintervention, and transabdominal secondary procedures (including
      laparoscopic branch vessel clipping) occurred in 55% in patients with type II
      endoleak at 3 years, compared to 15% in patients without any endoleak (p<0.0001).
      Conversion to open repair or post-EVAR rupture was not significantly associated
      with type II endoleaks. An independent association of device migration and
      expansion of the aneurysm with late conversion was observed. The cumulative
      incidence of aneurysm rupture at 3 years of follow-up was 1.2% for an annual rate
      of 0.4%. Variables that significantly and independently correlated with rupture
      were size of the aneurysm at preoperative measurement and device migration during
      follow-up. CONCLUSION: Endoleak type II may not be harmless as it was more
      frequently associated with enlargement of the aneurysm and reinterventions. Large
      aneurysms and migration of the device were the main risk factors for rupture. The
      clinical implications of these findings may involve more frequent surveillance
      visits for patients with type II endoleak. Aneurysm expansion is a clear
      indication for reintervention. Patients with large aneurysms, 65 mm or larger,
      may also benefit from a more comprehensive surveillance schedule.

PMID- 14718894
TI  - Visceral and renal tissue oxygenation during supraceliac aortic crossclamping and
      left heart bypass with selective organ perfusion.
AB  - INTRODUCTION: Left-heart bypass (LHB) and selective organ perfusion (SOP) are
      used during thoracoabdominal aortic surgery to prevent ischemic damage to the
      kidneys and visceral organs after supraceliac aortic crossclamping. We studied
      the hypothesis, in a porcine model, that despite LHB and maximal SOP, visceral
      and renal ischemia still occurred during surgery. MATERIAL AND METHODS: Eleven
      pigs (54-70 kg) were coupled to a non-pulsatile LHB with inflow and outflow at
      the lower thoracic and distal infrarenal aorta, respectively. After supracoeliac
      and infrarenal aortic crossclamping, SOP was started using perfusion catheters.
      The proximal and distal mean aortic blood pressures were kept above 70 and 50
      mmHg, respectively, while the mean blood pressure within the SOP system was above
      60 mmHg. The visceral and renal tissue oxygenation was measured by intermittent
      blood gas analysis, from the portal and both renal veins. The jejunal mucosal
      oxygenation was measured by tonometric measurement of the luminal pCO2. RESULTS:
      Measured median blood blood flow through the LHB and the SOP system were 800 and
      1140 ml/min, respectively. Median blood flow prior to, and during LHB and SOP
      through the celiac artery, superior mesenteric artery, and left renal artery were
      300 and 240, 762 and 295, and 235 and 235 ml/min, respectively. During 3 h of LHB
      and SOP no significant changes in the renal tissue oxygenation were noted
      compared with the physiological situation prior to supracoeliac aortic
      crossclamping and cannulation. However, in the visceral vascular bed median mixed
      venous oxygen saturation dropped from 79 to 63% (p<0.001), and median oxygen
      extraction ratio increased from 26 to 41% (p<0.001). Median tonometric measured
      intraluminal jejunal pCO2 increased from 9.9 to 12.15 kPa (p>0.05). During 3 h of
      LHB and SOP no hemolysis was detected, as there was no rise in serum LDH.
      CONCLUSION: LHB and SOP preserves renal but not visceral tissue oxygenation
      during supraceliac aortic crossclamping and does not induce hemolysis.

PMID- 14718895
TI  - Incidence of acute thrombo-embolic occlusion of the superior mesenteric artery--a
      population-based study.
AB  - OBJECTIVE: To determine the incidence of acute thrombo-embolic occlusion of the
      superior mesenteric artery (AOSMA) in a population-based study. MATERIAL: All
      clinical (n=23,446) and forensic (n=7569) autopsies performed in the city of
      Malmo between 1970 and 1982 (population 264,000-230,000 inhabitants). The autopsy
      rate was 87%. METHODS: Calculation of the incidence of AOSMA with intestinal
      gangrene in those autopsies coded for bowel ischaemia (997/23,446 clinical and
      9/7569 forensic autopsies). The operative procedures performed in 1970, 1976 and
      1982 were also analysed. RESULTS: Two forensic and 211 clinical autopsies
      demonstrated AOSMA with intestinal gangrene. Previous suspicion of intestinal
      ischaemia was noted in only 33%. Sixteen patients were operated. The cause
      specific mortality was 6.0/1000 deaths. The incidence was 8.6/100,000 person
      years, increasing exponentially with age (p<0.001). Mortality was 93%.
      CONCLUSIONS: The incidence and mortality of AOSMA is higher than previously
      reported from clinical series. There is seldom any suspicion of the diagnosis
      prior to death.

PMID- 14718896
TI  - Percutaneous transluminal renal angioplasty (PTRA) and surgical revascularisation
      in renovascular disease--a retrospective comparison of results, complications,
      and mortality.
AB  - OBJECTIVE: To evaluate results, complications and mortality following
      percutaneous transluminal renal angioplasty (PTRA) and open surgical
      revascularisation for renovascular disease. METHODS: A retrospective evaluation
      of 381 renovascular patients (median age 64, range 9-99 years, 152 women) treated
      at Malmo University Hospital during 1987-1996. Two hundred and sixty-two (69%) of
      the patients were treated with PTRA, 106 (28%) with open revascularisation.
      RESULTS: Thirty-day mortality was 2% in the PTRA group and 9% after open surgery
      (p<0.001). There were no differences between groups concerning the number of re
      do procedures, but first re-do was performed after seven (IQR 3-14) months in the
      PTRA group, and after 15 (IQR 10-44) months after open revascularisation
      (p<0.0001). After a median follow-up of 4 months (IQR 0-13) systolic and
      diastolic blood pressure (BP) had decreased (p<0.0001) in both groups. The number
      of antihypertensive drugs was reduced (p<0.0001) and S-creatinine levels were
      unchanged in both groups. Long-time survival assessed with log-rank analysis was
      better (p<0.01) in the PTRA group. The risk ratio for death with open
      revascularisation was 1.69 (p<0.01). CONCLUSIONS: In this retrospective
      comparison, PTRA was as effective as open revascularisation, with lower
      complication rate and lower early and long-time mortality, but with shorter time
      to first re-do.

PMID- 14718897
TI  - Management of extra-cranial vertebral artery injuries.
AB  - OBJECTIVES: To review the management of vertebral artery injuries, and the impact
      of pre-operative angiography. MATERIALS AND METHODS: A retrospective review was
      conducted of all patients with vertebral artery (VA) injuries admitted to Groote
      Schuur Hospital, Cape Town between January 1987 and December 2002. Patients
      presenting with uncontrolled active bleeding or haemodynamic instability with a
      poor response to resuscitation were taken immediately to surgery. Stable
      patients, including those who stabilised after simple resuscitation, with
      evidence of a vascular injury (a bruit or a large haematoma) or trans-cervical
      gunshot wounds, underwent routine aortic arch and selective angiography. RESULTS:
      One hundred and one patients with vertebral artery injuries were included in the
      study. Ninety-two patients sustained penetrating injuries (41 gunshot, 51 stab),
      three were iatrogenic and six due to blunt trauma. Angiography was performed as
      the primary investigation in 88 patients, while seven patients had angiography
      following surgery. Thirty-nine vertebral artery occlusions, 11 arteriovenous
      fistulae, two intimal injuries and 36 false aneurysms were identified. Thirty
      three radiological interventions were performed. There were 22 associated
      vascular injuries in 16 patients, 27 nerve injuries in 25 patients, 11 osseous
      injuries in nine patients and eight aerodigestive injuries. Seven patients died.
      CONCLUSIONS: Angiography and intervention is of great benefit in the diagnosis
      and management of traumatic vertebral artery injuries. Angiography often avoids
      unnecessary exploration and permits endovascular treatment.

PMID- 14718898
TI  - Carotid artery angioplasty for restenosis following endarterectomy.
AB  - INTRODUCTION: The higher complication rate associated with the surgical treatment
      of restenosis following carotid endarterectomy (CEA) has led several authors to
      advocate angioplasty as the treatment of choice in the management of restenosis.
      We describe our experience with internal carotid artery angioplasty for post
      endarterectomy restenosis over 7 years. PATIENTS AND METHODS: From January 1994
      to April 2001, all patients with a >90% restenosis following CEA were considered
      for angioplasty. Thirty angioplasties were carried out in 25 patients, 80%
      (24/30), for asymptomatic recurrent stenosis. There was no difference between
      those who had intervention for recurrent stenosis (n=31) and those who did not
      (n=545) in age, sex, smoking status or incidence of diabetes or hypertension. A
      significantly greater number of patients who underwent angioplasty were
      hypercholesterolaemic (p<0.05, Chi-squared test). RESULTS: Mean time from surgery
      to angioplasty was 13 months (range 1-23). Angioplasty was technically successful
      in 29 cases (97%). Three patients (10%) experienced transient neurological
      symptoms during the procedure. There were no strokes. Ninety-six percent (28/29)
      of patients were followed up with duplex scanning. Mean follow-up was 20 months
      (range 2-48). Three patients developed a greater than 90% restenosis. CONCLUSION:
      Angioplasty is an acceptable alternative to surgery in the management of internal
      carotid artery restenosis following endarterectomy.

PMID- 14718899
TI  - Frequency, clinical significance and course of cerebral ischemic events after
      carotid endarterectomy evaluated by serial diffusion weighted imaging.
AB  - OBJECTIVES: Neurological deficit defines the outcome of Carotid Endarterectomy
      (CEA) that is mainly caused by cerebral ischemia. Diffusion-weighted imaging
      (DWI) is a sensitive method for demonstrating even small ischemic lesions. The
      aim of this study was to evaluate the frequency, clinical significance and course
      of ischemic lesions after CEA using serial DWI. METHODS: DWI was performed within
      1 day before and after CEA in 88 patients. Postoperative lesions were analyzed by
      their quantity, volume and distribution. To differentiate temporary ischemia from
      definite cerebral infarction (blood brain barrier disruption) all patients with a
      positive postoperative DWI were reexamined with contrast-enhanced T1-MRI 7-10
      days after the procedure. All patients were examined by a neurologist within 2
      days before and after CEA. RESULTS: Two patients showed a postoperative
      neurological deficit. Postoperative DWI revealed ipsilateral ischemic lesions in
      15 patients. In seven of these patients a brain infarction was diagnosed on the
      T1-MRI during follow-up. A significant correlation between the number of DWI
      lesions (p=0.031) as well as the volume of DWI lesions (p=0.023) and definite
      infarction was found. Symptomatic patients preoperatively showed significantly
      more DWI lesions (p=0.036) and cerebral infarcts (p=0.003). CONCLUSION: DWI is a
      sensitive method of demonstrating ischemic events after CEA. The number and
      volume of DWI lesions after CEA are highly predictive of brain infarction.

PMID- 14718900
TI  - Selected haemostatic factors in carotid bifurcation plaques of patients
      undergoing carotid endarterectomy.
AB  - OBJECTIVE: To determine the concentration of selected haemostatic factors (HFs):
      thrombin-antithrombin complexes (TAT), antithrombin (AT), tissue plasminogen
      activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and D-dimers in
      carotid bifurcation plaques and to compare plaque composition in different
      subgroups of patients (mainly those with symptomatic and asymptomatic carotid
      stenosis). MATERIALS AND METHODS: Thirty-eight consecutive patients (20
      symptomatic, 18 asymptomatic) undergoing carotid endarterectomy were enrolled in
      the study. The concentration of selected HFs in carotid plaques was measured
      using mainly enzyme immunoassay (ELISA). Simultaneously, the concentration of HFs
      in plasma was also obtained. RESULTS: Symptomatic plaques contained significantly
      more TAT complexes (p=0.03). AT was found only in nine out of 38 carotid plaques
      and was present mainly in symptomatic carotid plaques (n=8/9)(p<0.006). No
      significant differences were found between symptomatic and asymptomatic carotid
      plaques with respect to t-PA, PAI-1 and D-dimers concentration. There was an
      increased concentration of TAT (p<0.001), t-PA (p<0.02) and D-dimers (p<0.02) in
      carotid plaques of diabetic patients. Patients with coexisting intermittent
      claudication had elevated levels of D-dimers in carotid plaques (p<0.02). The
      only positive correlation was demonstrated between the concentration of AT in
      plasma and carotid plaques (R=0.76; p=0.02). CONCLUSIONS: All the evaluated HFs
      are the components of a carotid plaque. Symptomatic patients have increased
      concentration of TAT complexes in a carotid plaque. The symptomatic carotid
      plaque contains AT more frequently, which correlates positively with AT plasma
      levels. The most marked changes in the carotid plaque haemostatic composition
      (expressed by elevated levels of TAT, t-PA and D-dimers) have diabetic patients.

PMID- 14718901
TI  - Does an adjuvant AV-fistula improve the patency of a femorocrural PTFE bypass
      with distal vein cuff in critical leg ischaemia?--a prospective randomised
      multicentre trial.
AB  - INTRODUCTION: A lack of suitable veins can cause serious problems when attempting
      to revascularise critically ischaemic legs. Prosthetic grafts have much worse
      patency in the femocrural position, despite the use of distal anastomotic cuffs.
      The use of adjuvant AV-fistula at the distal anastomosis should increase the
      graft flow above the thrombotic threshold velocity and thus increase prosthetic
      graft patency. AIM: The aim of the study was to evaluate the benefit of an
      adjuvant AV-fistula on the patency of a femorocrural PTFE bypass with a distal
      vein cuff. MATERIALS AND METHODS: This prospective randomised multicentre trial
      was conducted in four centres. A total of 59 patients with critical leg ischaemia
      and no suitable veins for grafting were randomised to receive a femocrural PTFE
      bypass and distal vein cuff, with or without an adjuvant AV-fistula. Thirty-one
      patients were randomised to the AV-fistula group (AVFG) and 28 to the control
      group (CG). Six patients were lost to follow-up during the 2-year study time.
      RESULTS: There were six immediate occlusions in each treatment group, but half of
      these were saved by re-operation. The mean postoperative ankle-brachial index
      (ABI) was 0.85 in the AVFG and 0.94 in the CG. The primary and secondary patency
      rate at 2 years was 29 and 40% for the AVFG and 36 and 40% for the CG (NS). Leg
      salvage at 2 years was 65 and 68%, respectively (NS). CONCLUSION: Adjuvant AV
      fistula does not improve the patency of a femorocrural PTFE bypass with a distal
      vein cuff.

PMID- 14718902
TI  - Activation of coagulation and fibrinolytic systems in patients with CLI is not
      normalized after surgical revascularisation.
AB  - OBJECTIVE: To study the activation of coagulation and fibrinolysis before, during
      and after surgical revascularisation in patients with critical limb ischemia
      (CLI). DESIGN: Prospective clinical study. MATERIALS AND METHODS: Forty patients
      with CLI underwent femoro-popliteal or femoro-distal reconstruction and were
      compared to a control-group. Measurements of prothrombin-fragment 1+2 (F1+2) and
      thrombin-antithrombin complex (TAT) assessed activation of coagulation.
      Fibrinolysis was determined by tissue plasminogen activator (tPA), plasminogen
      activator inhibitor (PAI-1) and fibrin degradation product (D-dimer). The
      inflammatory mediators: Interleukin 2 receptor (IL-2-rec), Interleukin 6 (IL-6),
      Interleukin 10 (IL-10) and Monocyte chemoattractant protein 1 (MCP-1) was also
      analysed. RESULTS: Patients (in 35 of the 40 reconstruction was possible) were
      operated upon using either vein (n=23) or ePTFE (n=12) grafts. Patients with CLI
      had a preoperative prothrombotic state as indicated by high TAT-levels and also
      ongoing fibrinolysis with high levels of t-PA and D-dimer. After reperfusion an
      ongoing prothrombotic state for the first week was demonstrated. A significant as
      well as defective fibrinolysis was also seen with increased levels of tPA and D
      dimer unopposed by PAI-1 after one week and also after 30 days. Increased levels
      of inflammatory mediators IL-6, IL-10 and MCP-1 was observed after reperfusion
      and normalised after 30 days. CONCLUSION: This study demonstrates significant
      disturbances of both the coagulation and fibrinolytic systems before, during and
      after revascularisation for CLI. This was accompanied by release of inflammatory
      mediators. A prothrombotic state and increased fibrinolysis were evident also 30
      days after successful revascularisation.

PMID- 14718903
TI  - Lower limb amputations in Southern Finland in 2000 and trends up to 2001.
AB  - OBJECTIVES: To assess the current incidence of major lower limb amputations in
      Southern Finland and epidemiological trends during the last 17 years. MATERIALS
      AND METHODS: In a retrospective survey for the year 2000 patient data was
      gathered from hospital records in the eight surgical hospitals in the area
      studied. Follow-up was 1 year. Amputation data for years 1984-1995 was gathered
      from reports done before at the same area and amputation figures for years 1990
      2001 also from the National Research and Development Centre for Welfare and
      Health. RESULTS: In year 2000, the incidence of major amputations was 154/million
      inhabitants. The reason for major amputation was chronic critical lower limb
      ischaemia in 71.8% and acute ischaemia in 16.5% of the cases. The below-knee
      (BK)/above-knee (AK) ratio was 0.76. After 1 year only 48% of the patients were
      alive. From 1984 to 2000 amputation incidence showed a decrease of 41%. The
      decline in age-adjusted amputation incidence from 1990 to 2000 was 30% and by
      2001 as much as 40%. There was a significant inverse correlation both between
      incidence of infrainguinal bypass and amputation (r=-0.682, p=0.021) and between
      infrapopliteal bypass and amputation (r=-0.682, p=0.021). CONCLUSIONS: There was
      a reduction in the number of amputations in Southern Finland during the past 17
      years. This occurred synchronously with the increase in vascular reconstructions.
      Our data suggests that vascular surgery saves patients from BK-amputations and
      therefore relative amount of AK-amputations inevitably rises.

PMID- 14718904
TI  - Chronic transcutaneous electrical stimulation of calf muscles improves functional
      capacity without inducing systemic inflammation in claudicants.
AB  - OBJECTIVES: To assess whether electrical stimulation of ischaemic calf muscles in
      claudicants causes a systemic inflammatory response and to evaluate effects of
      its chronic application on muscle function and walking ability. DESIGN:
      Prospective randomised controlled trial of calf muscle stimulation. MATERIALS AND
      METHODS: Stable claudicants were randomised to receive either active chronic low
      frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor
      transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one
      leg, 3 x 20 min per day for four weeks. Leucocyte activation was quantified by
      changes in cell morphology, vascular permeability by urinary albumin:creatinine
      ratio (ACR), calf muscle function by isometric twitch contractions and walking
      ability by treadmill performance pre- and post-intervention. RESULTS: Acute
      active muscle stimulation activated leucocytes less (28% increase) than a
      standard treadmill test (81% increase) and did not increase ACR. Chronic calf
      muscle stimulation significantly increased pain-free walking distance by 35 m
      (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70,
      P<0.05) while control treatment had no effect. Active stimulation prevented
      fatigue of calf muscles during isometric electrically evoked contractions by
      abolishing the slowing of relaxation that was responsible for loss of force.
      CONCLUSIONS: Chronic electrical muscle stimulation is an effective treatment for
      alleviating intermittent claudication which, by targeted activation of a small
      muscle mass, does not engender a significant systemic inflammatory response.

PMID- 14718905
TI  - Arterial and venous reconstruction for free tissue transfer in diabetic ischemic
      foot ulcers.
AB  - OBJECTIVE: To review our experience with temporary arteriovenous (AV) fistula
      followed by free tissue transfer in the treatment of diabetic foot ulcers
      associated with peripheral arterial occlusion. PATIENTS AND METHOD: From July
      1997 to July 2002, 15 lower extremities were operated in 14 patients. An AV loop
      with its apex below the medial malleolus was created between popliteal artery and
      saphenous system. Three weeks later, the loop was divided to provide an artery
      and a vein end. Foot defect was covered with latissimus dorsi muscle flap
      followed by split thickness skin grafting. RESULTS: Fistulas were patent in 12
      extremities. Free tissue transfer was performed in 13 extremities. Two free flaps
      failed. After patent temporary arteriovenous fistula, free tissue transfer was
      successful in 11 of 12 extremities. One patient was amputated below knee due to
      ongoing infection despite successful free tissue transfer. Early mortality rate
      was 7%. Limb salvage was achieved in 11 of 13 extremities that staged operation
      was performed. Overall extremity loss was four of 15 lower extremities in 14
      patients. Overall mortality was 21% for mean 20 follow-up period. CONCLUSION:
      Temporary AV fistula and free flap may provide stable wound coverage and high
      rate of limb salvage in treatment of diabetic foot ulcers with large tissue loss.

PMID- 14718906
TI  - Accuracy of clinical data in a population based vascular registry.
AB  - INTRODUCTION: Clinical databases are increasingly being employed to evaluate the
      quality of treatments, including patients with peripheral vascular disease. Valid
      data is vital to the value of these analyses. OBJECTIVE: To assess the validity
      of clinical data in a population-based national vascular registry. DESIGN:
      Traditional reproducibility study was supplemented by refilling of data by an
      independent observer, thereby creating three data sets for comparison. MATERIALS
      AND METHODS: Twenty prospectively recorded electronic forms from each department
      were selected randomly from the Danish National Vascular Registry. Data forms
      were refilled by the surgeons of the department concerned, and by an independent
      member of the board of the Danish National Vascular Registry. Refilling was
      performed blinded to the original forms. CONCLUSIONS: A high degree of accuracy
      of clinical data can be achieved. An independent observer makes it possible to
      evaluate the classification of observer dependent parameters and explain
      differences in the reproducibility of data.

PMID- 14718907
TI  - Coronary subclavian steal syndrome.
AB  - Inappropriate alterations in flow in the form of steal syndromes are a well
      recognised phenomenon. In the subclavian steal syndrome a proximal subclavian
      artery stenosis is responsible for reversal of flow in the vertebral artery and
      symptoms of vertebrobasilar ischaemia occur with arm movement. After internal
      mammary artery grafting to the coronary circulation, during coronary artery
      bypass surgery (CABG), coronary subclavian steal can occur. Retrograde flow
      occurs from the myocardium through the internal mammary graft to the subclavian
      artery secondary to a proximal subclavian stenosis. It is a rare but important
      cause of recurrent chest pain after coronary surgery.

PMID- 14718908
TI  - A case report of intentional occlusion of an aberrant right subclavian artery
      during endovascular stent-graft repair of a descending aortic aneurysm.

PMID- 14718911
TI  - STAR-studded circuitry.

PMID- 14718912
TI  - Sculpting a domain by splicing.

PMID- 14718913
TI  - Timing the catch.

PMID- 14718914
TI  - E3 ligase activity and suppression of breast cancer.

PMID- 14718915
TI  - Taking Drosophila Rad51 for a SPiN.

PMID- 14718917
TI  - Whither structural biology?

PMID- 14718918
TI  - Challenge your teaching.

PMID- 14718919
TI  - RNA target specificity of the STAR/GSG domain post-transcriptional regulatory
      protein GLD-1.
AB  - The post-transcriptional regulation of gene expression underlies several critical
      developmental phenomena. In metazoa, gene products that are expressed, silenced
      and packaged during oogenesis govern early developmental processes prior to
      nascent transcription activation. Furthermore, tissue-specific alternative
      splicing of several transcription factors controls pattern formation and organ
      development. A highly conserved family of proteins containing a STAR/GSG RNA
      binding domain is essential to both processes. Here, we identify the consensus
      STAR-binding element (SBE) required for specific mRNA recognition by GLD-1, a key
      regulator of Caenorhabditis elegans germline development. We have identified and
      verified new GLD-1 repression targets containing this sequence. The results
      suggest additional functions of GLD-1 in X-chromosome silencing and early
      embryogenesis. The SBE is present in Quaking and How mRNA targets, suggesting
      that STAR protein specificity is highly conserved. Similarities between the SBE
      and the branch-site signal indicate a possible competition mechanism for STAR/GSG
      regulation of splicing variants.

PMID- 14718920
TI  - Adenine riboswitches and gene activation by disruption of a transcription
      terminator.
AB  - A class of riboswitches that recognizes guanine and discriminates against other
      purine analogs was recently identified. RNAs that carry the consensus sequence
      and structural features of guanine riboswitches are located in the 5'
      untranslated region (UTR) of numerous prokaryotic genes, where they control the
      expression of proteins involved in purine salvage and biosynthesis. We report
      that three representatives of this riboswitch class bind adenine with values for
      apparent dissociation constant (apparent K(d)) that are several orders of
      magnitude lower than those for binding guanine. Because preference for adenine is
      attributable to a single nucleotide substitution, the RNA most likely recognizes
      its ligand by forming a Watson-Crick base pair. In addition, the adenine
      riboswitch associated with the ydhL gene of Bacillus subtilis functions as a
      genetic 'on' switch, wherein adenine binding causes a structural rearrangement
      that precludes formation of an intrinsic transcription terminator stem.

PMID- 14718921
TI  - PIP2 increases the speed of response of synaptotagmin and steers its membrane
      penetration activity toward the plasma membrane.
AB  - Synaptotagmin-1 (syt), the putative Ca2+ sensor for exocytosis, is anchored to
      the membrane of secretory organelles. Its cytoplasmic domain is composed of two
      Ca2+-sensing modules, C2A and C2B. Syt binds phosphatidylinositol 4,5
      bisphosphate (PIP2), a plasma membrane lipid with an essential role in exocytosis
      and endocytosis. We resolved two modes of PIP2 binding that are mediated by
      distinct surfaces on the C2B domain of syt. A novel Ca2+-independent mode of
      binding predisposes syt to penetrate PIP2-harboring target membranes in response
      to Ca2+ with submillisecond kinetics. Thus, PIP2 increases the speed of response
      of syt and steers its membrane-penetration activity toward the plasma membrane.
      We propose that syt-PIP2 interactions are involved in exocytosis by facilitating
      the close apposition of the vesicle and target membrane on rapid time scales in
      response to Ca2+.

PMID- 14718922
TI  - A conformational switch in the Piccolo C2A domain regulated by alternative
      splicing.
AB  - C2 domains are widespread Ca2+-binding modules. The active zone protein Piccolo
      (also known as Aczonin) contains an unusual C2A domain that exhibits a low
      affinity for Ca2+, a Ca2+-induced conformational change and Ca2+-dependent
      dimerization. We show here that removal of a nine-residue sequence by alternative
      splicing increases the Ca2+ affinity, abolishes the conformational change and
      abrogates dimerization of the Piccolo C2A domain. The NMR structure of the Ca2+
      free long variant provides a structural basis for these different properties of
      the two splice forms, showing that the nine-residue sequence forms a beta-strand
      otherwise occupied by a nonspliced sequence. Consequently, Ca2+-binding to the
      long Piccolo C2A domain requires a marked rearrangement of secondary structure
      that cannot occur for the short variant. These results reveal a novel mechanism
      of action of C2 domains and uncover a structural principle that may underlie the
      alteration of protein function by short alternatively spliced sequences.

PMID- 14718923
TI  - Structural basis for dipeptide amide isoform-selective inhibition of neuronal
      nitric oxide synthase.
AB  - Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate nitric
      oxide (NO) crucial to the cardiovascular, nervous and host defense systems,
      respectively. Development of isoform-selective NOS inhibitors is of considerable
      therapeutic importance. Crystal structures of nNOS-selective dipeptide inhibitors
      in complex with both nNOS and eNOS were solved and the inhibitors were found to
      adopt a curled conformation in nNOS but an extended conformation in eNOS. We
      hypothesized that a single-residue difference in the active site, Asp597 (nNOS)
      versus Asn368 (eNOS), is responsible for the favored binding in nNOS. In the
      D597N nNOS mutant crystal structure, a bound inhibitor switches to the extended
      conformation and its inhibition of nNOS decreases >200-fold. Therefore, a single
      residue difference is responsible for more than two orders of magnitude
      selectivity in inhibition of nNOS over eNOS by L-N(omega)-nitroarginine
      containing dipeptide inhibitors.

PMID- 14718924
TI  - The structural basis for substrate and inhibitor selectivity of the anthrax
      lethal factor.
AB  - Recent events have created an urgent need for new therapeutic strategies to treat
      anthrax. We have applied a mixture-based peptide library approach to rapidly
      determine the optimal peptide substrate for the anthrax lethal factor (LF), a
      metalloproteinase with an important role in the pathogenesis of the disease.
      Using this approach we have identified peptide analogs that inhibit the enzyme in
      vitro and that protect cultured macrophages from LF-mediated cytolysis. The
      crystal structures of LF bound to an optimized peptide substrate and to peptide
      based inhibitors provide a rationale for the observed selectivity and may be
      exploited in the design of future generations of LF inhibitors.

PMID- 14718925
TI  - Identification of small molecule inhibitors of anthrax lethal factor.
AB  - The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin
      composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF
      is a Zn-dependent metalloprotease that inactivates key signaling molecules, such
      as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell
      death. We report here the identification of small molecule (nonpeptidic)
      inhibitors of LF. Using a two-stage screening assay, we determined the LF
      inhibitory properties of 19 compounds. Here, we describe six inhibitors on the
      basis of a pharmacophoric relationship determined using X-ray crystallographic
      data, molecular docking studies and three-dimensional (3D) database mining from
      the US National Cancer Institute (NCI) chemical repository. Three of these
      compounds have K(i) values in the 0.5-5 microM range and show competitive
      inhibition. These molecular scaffolds may be used to develop therapeutically
      viable inhibitors of LF.

PMID- 14718926
TI  - Dynamic changes in transcription factor complexes during erythroid
      differentiation revealed by quantitative proteomics.
AB  - During erythroid differentiation, beta-globin gene expression is regulated by the
      locus control region (LCR). The transcription factor NF-E2p18/MafK binds within
      this region and is essential for beta-globin expression in murine erythroleukemia
      (MEL) cells. Here we use the isotope-coded affinity tag (ICAT) technique of
      quantitative mass spectrometry to compare proteins interacting with NF-E2p18/MafK
      during differentiation. Our results define MafK as a 'dual-function' molecule
      that shifts from a repressive to an activating mode during erythroid
      differentiation. The exchange of MafK dimerization partner from Bach1 to NF-E2p45
      is a key step in the switch from the repressed to the active state. This shift is
      associated with changes in the interaction of MafK with co-repressors and co
      activators. Thus, our results suggest that in addition to its role as a cis
      acting activator of beta-globin gene expression in differentiated erythroid
      cells, the LCR also promotes an active repression of beta-globin transcription in
      committed cells before terminal differentiation.

PMID- 14718927
TI  - A mechanical unfolding intermediate in an actin-crosslinking protein.
AB  - Many F-actin crosslinking proteins consist of two actin-binding domains separated
      by a rod domain that can vary considerably in length and structure. In this
      study, we used single-molecule force spectroscopy to investigate the mechanics of
      the immunoglobulin (Ig) rod domains of filamin from Dictyostelium discoideum
      (ddFLN). We find that one of the six Ig domains unfolds at lower forces than do
      those of all other domains and exhibits a stable unfolding intermediate on its
      mechanical unfolding pathway. Amino acid inserts into various loops of this
      domain lead to contour length changes in the single-molecule unfolding pattern.
      These changes allowed us to map the stable core of approximately 60 amino acids
      that constitutes the unfolding intermediate. Fast refolding in combination with
      low unfolding forces suggest a potential in vivo role for this domain as a
      mechanically extensible element within the ddFLN rod.

PMID- 14718928
TI  - Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1.
AB  - Recruitment of the GRIP domain golgins to the trans-Golgi network is mediated by
      Arl1, a member of the ARF/Arl small GTPase family, through interaction between
      their GRIP domains and Arl1-GTP. The crystal structure of Arl1-GTP in complex
      with the GRIP domain of golgin-245 shows that Arl1-GTP interacts with the GRIP
      domain predominantly in a hydrophobic manner, with the switch II region
      conferring the main recognition surface. The involvement of the switch and
      interswitch regions in the interaction between Arl1-GTP and GRIP accounts for the
      specificity of GRIP domain for Arl1-GTP. Mutations that abolished the Arl1
      mediated Golgi localization of GRIP domain golgins have been mapped on the
      interface between Arl1-GTP and GRIP. Notably, the GRIP domain forms a homodimer
      in which each subunit interacts separately with one Arl1-GTP. Mutations
      disrupting the GRIP domain dimerization also abrogated its Golgi targeting,
      suggesting that the dimeric form of GRIP domain is a functional unit.

PMID- 14718929
TI  - The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.
AB  - Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that
      transforms penicillins into cephalosporins by inserting a carbon atom into the
      penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate
      produce a reactive iron-oxygen species, succinate and CO2. The oxidizing iron
      species subsequently reacts with penicillin to give cephalosporin and water. Here
      we describe high-resolution structures for ferrous DAOCS in complex with
      penicillins, the cephalosporin product, the cosubstrate and the coproduct. Steady
      state kinetic data, quantum-chemical calculations and the new structures indicate
      a reaction sequence in which a 'booby-trapped' oxidizing species is formed. This
      species is stabilized by the negative charge of succinate on the iron. The
      binding sites of succinate and penicillin overlap, and when penicillin replaces
      succinate, it removes the stabilizing charge, eliciting oxidative attack on
      itself. Requisite groups of penicillin are within 1 A of the expected position of
      a ferryl oxygen in the enzyme-penicillin complex.

PMID- 14718933
TI  - Provision of genetic services in Europe: current practices and issues.

PMID- 14718934
TI  - Population genetic screening programmes: technical, social and ethical issues.

PMID- 14718935
TI  - Data storage and DNA banking for biomedical research: technical, social and
      ethical issues.

PMID- 14718936
TI  - Genetic information and testing in insurance and employment: technical, social
      and ethical issues.

PMID- 14718937
TI  - Provision of genetic services in Europe: current practices and issues.
AB  - This paper examines the professional and scientific views on the social, ethical
      and legal issues that impact on the provision of genetic services in Europe. Many
      aspects have been considered, such as the definition and the aims of genetic
      services, their organization, the quality assessment, public education, as well
      as the partnership with patients support groups and the multicultural aspects.
      The methods was primarily the analysis of professional guidelines, legal
      frameworks and other documents related to the organization of genetic services,
      mainly from Europe, but also from USA and international organizations. Then, the
      method was to examine the background data emerging from an updated report
      produced by the Concerted Action on Genetic Services in Europe, as well as the
      issues debated by 43 experts from 17 European countries invited to an
      international workshop organized by the European Society of Human Genetics Public
      and Professional Policy Committee in Helsinki, Finland, 8 and 9 September 2000.
      Some conclusions were identified from the ESHG workshop to arrive at outlines for
      optimal genetic services. Participants were concerned about equal accessibility
      and effectiveness of clinical genetic services, quality assessment of services,
      professional education, multidisciplinarity and division of tasks as well as
      networking. Within European countries, adherence to the organizational principles
      of prioritization, regionalization and integration into related health services
      would maximize equal accessibility and effectiveness of genetic actions. There is
      a need for harmonization of the rules involved in financial coverage of DNA tests
      in order to make these available to all Europeans. Clear guidelines for the best
      practice will ensure that the provision of genetic services develops in a way
      that is beneficial to its customers, be they health professionals or the public,
      especially since the coordination of clinical, laboratory and research
      perspectives within a single organizational structure permits a degree of
      coherence not often found in other specialties.

PMID- 14718938
TI  - Population genetic screening programmes: principles, techniques, practices, and
      policies.
AB  - This paper examines the professional and scientific views on the principles,
      techniques, practices, and policies that impact on the population genetic
      screening programmes in Europe. This paper focuses on the issues surrounding
      potential screening programmes, which require further discussion before their
      introduction. It aims to increase, among the health-care professions and health
      policy-makers, awareness of the potential screening programmes as an issue of
      increasing concern to public health. The methods comprised primarily the review
      of the existing professional guidelines, regulatory frameworks and other
      documents related to population genetic screening programmes in Europe. Then, the
      questions that need debate, in regard to different types of genetic screening
      before and after birth, were examined. Screening for conditions such as cystic
      fibrosis, Duchenne muscular dystrophy, familial hypercholesterolemia, fragile X
      syndrome, hemochromatosis, and cancer susceptibility was discussed. Special
      issues related to genetic screening were also examined, such as informed consent,
      family aspects, commercialization, the players on the scene and monitoring
      genetic screening programmes. Afterwards, these questions were debated by 51
      experts from 15 European countries during an international workshop organized by
      the European Society of Human Genetics Public and Professional Policy Committee
      in Amsterdam, The Netherlands, 19-20, November, 1999. Arguments for and against
      starting screening programmes have been put forward. It has been questioned
      whether genetic screening differs from other types of screening and testing in
      terms of ethical issues. The general impression on the future of genetic
      screening is that one wants to 'proceed with caution', with more active impetus
      from the side of patients' organizations and more reluctance from the policy
      makers. The latter try to obviate the potential problems about the abortion and
      eugenics issues that might be perceived as a greater problem than it is in
      reality. However, it seems important to maintain a balance between a
      'professional duty of care' and 'personal autonomy'.

PMID- 14718939
TI  - Data storage and DNA banking for biomedical research: informed consent,
      confidentiality, quality issues, ownership, return of benefits. A professional
      perspective.
AB  - The purpose of this paper is to formulate a professional and scientific view on
      the social, ethical, and legal issues that impact on data storage and DNA banking
      practices for biomedical research in Europe. Many aspects have been considered,
      such as the requirements for data storage and DNA banking in the public and
      private sectors in Europe and the issues relating to DNA banking, that is to say
      the consent requirements for the banking and further uses of DNA samples, their
      control and ownership, and the return of benefit derived from DNA exploitation to
      the community. The methods comprise primarily the review of the existing
      professional guidelines, legal frameworks and other documents related to the data
      storage and DNA banking practices in public and private sectors in Europe. Then,
      the issues related to DNA banking were examined during an international workshop
      organized by the European Society of Human Genetics Public and Professional
      Policy Committee in Paris, France, 07-08, April, 2000. A total of 50 experts from
      12 European countries attended this workshop. It came out that DNA banking for
      medical and research purposes is indispensable. It facilitates the constitution
      of large collections, sharing of samples, multiple testing on the same samples,
      and repeating testing over the years. However, banking organization is complex,
      requires multiple actors, and concerns are expressed in various countries.
      International standardization of ethical requirements and policies with regard to
      DNA banking has been recommended. Such standardization would facilitate a greater
      protection of individuals as well as future international cooperation in
      biomedical research.

PMID- 14718940
TI  - Genetic information and testing in insurance and employment: technical, social
      and ethical issues.
AB  - The present paper examines the professional and scientific views on the social,
      ethical and legal issues that impact on genetic information and testing in
      insurance and employment in Europe. For this purpose, many aspects have been
      considered, such as the concerns of medical geneticists, of the insurers and
      employers, of the public, as well as the regulatory frameworks and unresolved
      issues. The method used was primarily the review of the technical, social,
      economical and ethical aspects of advances in genetics and the concerns of
      parties who are involved, that is, the insurers, the employers and the public.
      The existing guidelines and legislation on this topic were also reported. Then,
      the method was to examine the issues debated by these parties in Europe, as well
      as by 47 experts from 14 European countries invited to an international workshop
      organized by the European Society of Human Genetics Public and Professional
      Policy Committee in Manchester, UK, 25-27 February 2000. The result of this was
      that the most important issues raised by genetic information and testing in
      insurance and employment in Europe include a need for clear definitions of terms
      used in genetics, declaring the grounds on which genetic information is or is not
      used, and promoting confidence between the public and the insurance industry.
      There is currently very little use of genetic information in relation to
      employment, but the situation should be kept under review.

PMID- 14718941
TI  - Readable writing.

PMID- 14718943
TI  - View with a pinch of salt?

PMID- 14718953
TI  - Maintaining dental education and specialist dental care during an outbreak of a
      new coronavirus infection. Part 2: Control of the disease, then elimination.

PMID- 14718954
TI  - Orthodontics. Part 4: Treatment planning.
AB  - The treatment plan is an integral part of orthodontic management. It should be
      divided into both treatment aims (what do you want to do?) and plan (how are you
      going to do it?). The treatment aims will include, for example overjet reduction.
      The plan will consider how to create space in order to accomplish this as well as
      the appliance system that will be used.

PMID- 14718955
TI  - Adverse reactions to protective gloves used in the dental profession: experience
      of the UK Adverse Reaction Reporting Project.
AB  - The Adverse Reaction Reporting Project (ARRP) was set up to measure the extent
      and severity of adverse reactions to dental materials in the UK. Further analysis
      into the use of protective gloves has been carried out to establish the degree to
      which gloves are having a deleterious effect on the dental profession. In
      addition the survey aimed to establish the techniques used to manage adverse
      reactions and their effectiveness. In a 23-month period, 369 reports were
      received concerning adverse reactions to protective gloves used in dental
      practices. Reporters were contacted for further information, and a 92% response
      rate was achieved. The 330 reports analysed showed dentists to be the largest
      group to report adverse reactions, whilst dental technicians reported the fewest.
      The referral rate for staff and patients was similar with a third of adverse
      reactions being referred (n=110) to a specialist for diagnosis. A confirmed
      diagnosis was received in 65% of referred cases (n=72), but the symptoms reported
      suggested a larger degree of Type I reactions occurring than diagnosed. The use
      of non-powdered gloves appeared to be favoured over powdered gloves in 42% of
      glove changes, and nitrile gloves were used as an alternative to latex in 39% of
      changes. In conclusion, the results from this survey showed that wearing gloves
      in dental practices in the UK caused a range of adverse reactions. In 79% (n=330)
      of cases reported and analysed, these reactions were readily resolved or improved
      by self-medication, prescribed medication and/or changing to a different type of
      protective glove.

PMID- 14718956
TI  - Lack of tooth eruption following maxillary fracture: case report.
AB  - Aberrant tooth development following facial fractures is unusual. It is commonly
      reported that tooth buds involved in the line of a mandibular fracture will
      continue to develop normally and erupt sequentially. Few cases have been cited
      regarding developing teeth in the line of maxillary fractures. In the case
      reported, the normal growth and position of a maxillary third molar can be seen
      to be retarded at the position of a maxillary fracture, sustained by a child in
      the mixed dentition phase of dental development.

PMID- 14718964
TI  - Staphylococcus aureus in the oral cavity: a three-year retrospective analysis of
      clinical laboratory data.
AB  - OBJECTIVE: A retrospective analysis of laboratory data to investigate the
      isolation of Staphylococcus aureus from the oral cavity and facial area in
      specimens submitted to a regional diagnostic oral microbiology laboratory.
      METHODS: A hand search of laboratory records for a three-year period (1998-2000)
      was performed for specimens submitted to the regional diagnostic oral
      microbiology laboratory based at Glasgow Dental Hospital and School. Data were
      collected from forms where S. aureus was isolated. These data included
      demographics, referral source, specimen type, methicillin susceptibility and
      clinical details. RESULTS: For the period 1998-2000, there were 5,005 specimens
      submitted to the laboratory. S. aureus was isolated from 1,017 specimens, of
      which 967 (95%) were sensitive to methicillin (MSSA) and 50 (5%) were resistant
      to methicillin (MRSA). The 1,017 specimens were provided from 615 patients. MRSA
      was isolated from 37 (6%) of patients. There was an increasing incidence of S.
      aureus with age, particularly in the >70 years age group. The most common
      specimen from which MSSA was isolated was an oral rinse (38%) whilst for MRSA
      isolates this was a tongue swab (28%). The clinical condition most commonly
      reported for MSSA isolates was angular cheilitis (22%). Erythema, swelling, pain
      or burning of the oral mucosa was the clinical condition most commonly reported
      for MRSA isolates (16%). Patients from whom the MSSA isolates were recovered were
      most commonly (55%) seen in the oral medicine clinic at the dental hospital,
      whilst patients with MRSA were more commonly seen in primary care settings such
      as nursing homes, hospices and general dental practice (51%). CONCLUSION: In line
      with more recent surveys, this retrospective study suggests that S. aureus may be
      a more frequent isolate from the oral cavity than hitherto suspected. A small
      proportion of the S. aureus isolates were MRSA. There were insufficient data
      available to determine whether the S. aureus isolates were colonising or
      infecting the oral cavity. However, the role of S. aureus in several diseases of
      the oral mucosa merits further investigation.

PMID- 14718965
TI  - The planning, contracting and monitoring of orthodontic services, and the use of
      the IOTN index: a survey of consultants in dental public health in the United
      Kingdom.
AB  - OBJECTIVES: To establish which factors are used in planning, contracting and
      monitoring orthodontic services in the United Kingdom. In addition, the study
      investigated the value of the Index of Orthodontic Treatment Need (IOTN) as an
      instrument for planning orthodontic provision. METHODS: A structured
      questionnaire was sent to all consultants in dental public health in the United
      Kingdom. RESULTS: Over 80% of the respondents used the Index of Orthodontic
      Treatment Need (IOTN) as an instrument for planning, contracting and monitoring
      orthodontic services. Seventy per cent of these consultants regarded the IOTN
      index as a useful or very useful instrument. The main strength reported was that
      the IOTN index allows prioritisation (25.0%). The main weakness reported was that
      the index does not assess complexity (70.5%). CONCLUSIONS: Consultants in dental
      public health perceived the IOTN as a useful tool for planning orthodontic
      provision despite some shortcomings.

PMID- 14718966
TI  - Molar apicectomy with amalgam root-end filling: results of a prospective study in
      two district general hospitals.
AB  - AIM: To determine the five-year success rates, site or sites of failure,
      prognostic indicators and lower lip morbidity associated with molar apicectomy
      using amalgam root-end filling. DESIGN: Multicentre, prospective study. SETTING:
      The departments of oral and maxillo-facial surgery in two district general
      hospitals. METHOD: One thousand and seven molar apicectomy procedures, combined
      with amalgam root-end filling were expedited during the period 1974-1995. A five
      year review of each operated tooth was carried out or attempted between 1979
      2000. RESULTS: Of the 790 (78%) operated molars successfully reviewed at 5 years
      or later 451 (57%) exhibited 'complete healing' and 39 (5%) 'uncertain healing'.
      Three hundred (38%) were classified as 'unsatisfactory healing' (failures), and
      these included 12 which were assumed to be of periodontal origin. Whilst
      longitudinal root fracture, perforation and/or infection in the furcation,
      periodontal disease or a non-restorable crown accounted for treatment failure and
      often the need to remove teeth subsequently, the study probably pointed to the
      apical ends of the roots rather than the furcation as being the major sites at
      which 'unsatisfactory healing' occurred. Mandibular first molars attracted the
      highest 'complete healing' rate (60%) and mandibular second molars the lowest
      (46%). 'Good' root canal treatment (RCT) at the outset improved the prognosis of
      a root-end filling (REF) whilst the absence of RCT compromised it. Cystic change
      pointed to a better prognosis than apical granulomatous change as did a deep
      compared with a shallow 'bone cuff'. Disease at the furcation suggested a worse
      prognosis. Teeth which showed 'complete healing' at 1 year had a 75% probability
      of maintaining this outcome at 5 years. Sensory disturbance of variable duration
      occurred in the lower lip following 20-21% of mandibular molar procedures. In the
      majority of cases (79-80%) this had remitted within 3 months. A permanent deficit
      occurred in 8 patients (1%) where the apicectomy could definitely be incriminated
      as causative. Four were associated with first molar apicectomy and four with
      second molar apicectomy. CONCLUSIONS: Molar apicectomy with amalgam root-end
      filling attracts an overall 'complete healing' rate at 5 years of 57%, the
      results being best with mandibular first molars and worst with mandibular second
      molars. The prognosis is also better where there is 'good' initial orthograde
      root filling, an associated radicular cyst as compared with granulomatous change
      and where the buccal sulcus is deep rather than shallow. It is worse when
      orthograde root filling is absent and when there is disease in the furcation.
      'Complete healing' at 1 year can be expected to be maintained at 5 years in 75%
      of cases. The commonest site of subsequent periradicular rarefaction seems to be
      'apical' whilst failure at the furcation is probably comparatively rare. There is
      a threefold increase in the occurrence of permanent lower lip sensory impairment
      following second molar surgery in comparison with first molar surgery, the
      overall incidence being 1%.

PMID- 14718984
TI  - Change is, at last, an option.

PMID- 14718985
TI  - What's my motivation here?

PMID- 14718986
TI  - Why we must keep on talking.

PMID- 14718987
TI  - Consumers and healthcare.

PMID- 14718988
TI  - Fees for specialists.

PMID- 14718989
TI  - Overbrushing challenge.

PMID- 14718990
TI  - Prevention.

PMID- 14718991
TI  - Buyers beware!

PMID- 14718992
TI  - CPD papers.

PMID- 14719003
TI  - NHS Dentistry: Options for Change. Impressions one year on.

PMID- 14719004
TI  - NHS Dentistry: Options for Change in context--a personal overview of a landmark
      document and what it could mean for the future of dental services.
AB  - The aims of this paper are to provide an impartial overview of the proposals and
      agenda for the future brought together in the NHS Dentistry: Options for Change
      document in the context of previous dental service delivery in primary care, and
      to start to explore what Options for Change could mean for the future of NHS
      dental services. Options has been described as perhaps the most radical and
      ground breaking opportunity for NHS dentistry to finally move forward after
      prolonged periods of stagnation and disharmony. The Options agenda has the
      potential to bring in a new style of NHS practice for dentistry, providing a way
      to finally get off the current 'treadmill' and to develop new NHS dental services
      where prevention is a priority and providing high quality dental treatment,
      tailored to the long term needs of the 21st century patient, is the driving aim.
      However, the difficulties on all sides of leaving behind decades of disputes and
      overcoming real access, workforce and funding issues must not be underestimated
      or dismissed. The report was prepared by a working group comprising
      representatives from the profession, of patient groups and various sections of
      the Department of Health in England which was brought together by the then Chief
      Dental Officer. The key themes and priorities for action identified in Options
      include: local commissioning and funding, methods of remuneration for general
      dental practitioners, prevention and an oral health assessment for patients,
      clinical pathways, information and communication technology, practice structure,
      development of the dental team and the patient experience. The document also
      contains comprehensive reports of the three Options for Change task groups making
      recommendations for: 1) a new deal for patients - national standards, 2) systems
      of delivery of dental care and 3) education, training and development of the
      dental team. Ways forward for delivering improved, modern, effective, preventive,
      patient-centred dental care have been identified. This potential can, however,
      only be realised if viable and sustainable agreements can be achieved to
      operationalise the best choices.

PMID- 14719005
TI  - The health and social care bill.

PMID- 14719006
TI  - National evaluation of personal dental services (PDS) pilots: main findings and
      policy implications.

PMID- 14719007
TI  - Evaluation of personal dental services (PDS) first wave pilots: the alternative
      to general dental services (GDS) offered by the capitation-based pilots.

PMID- 14719008
TI  - National evaluation of personal dental services: the perspective of dentists and
      professionals complementary to dentistry.

PMID- 14719009
TI  - National evaluation of personal dental services: a qualitative investigation into
      patients' perceptions of dental services.

PMID- 14719025
TI  - Cobblers--a Christmas story for the chairside.

PMID- 14719026
TI  - Effects of pentobarbital on purinergic P2X receptors of rat dorsal root ganglion
      neurons.
AB  - Purinergic P2X receptors are ligand-gated ion channels that are activated by
      extracellular adenosine triphosphate (ATP) and are widely expressed not only in
      the central and peripheral nervous system but also in tissues throughout the
      body, playing an important role in the transfer of nociceptive information. Since
      the influence of barbiturates on P2X receptor subtypes is not known, we studied
      the effects of pentobarbital sodium (PB) on ATP responses in dorsal root ganglion
      (DRG) neurons. DRG neurons were dissected from 10- to 14-day-old rats and
      dissociated after enzyme treatment. Electrical measurements were performed using
      the nystatin-perforated patch recording mode under voltage-clamp conditions.
      Drugs were applied using the Y-tube method. ATP evoked three types of inward
      current at -60 mV: fast desensitizing, slow desensitizing, and mixed. The fast
      type current was attributed to activation of P2X3 subtype and the slow type to
      the P2X2 subtype. PB suppressed the fast-type current in a concentration
      dependent manner, while the slow type was slightly reduced. A noncompetitive
      inhibition was suggested by a downward shift of the ATP concentration-response
      curves. The current-voltage relationships showed inward rectification, and the
      extent of suppression was not affected by the holding potential. The reduction
      was greater in external solutions of higher pH. PB had subtype-specific effects
      on P2X receptors. The ionized form is likely to be responsible for the
      suppression of the P2X3 receptor current, which may result in a reduction of the
      excitability of central and peripheral neurons and may contribute to the
      anesthetic and analgesic actions of the agent.

PMID- 14719027
TI  - Coexistence of potentiation and low-frequency fatigue during voluntary exercise
      in human skeletal muscle.
AB  - The role of muscle potentiation in overcoming low-frequency fatigue (LFF) as it
      developed during submaximal voluntary exercise was investigated in eight males
      (age 26.4 +/- 0.7 years, mean +/- SE) performing isometric leg extension at
      approximately 30% of maximal voluntary contraction for 60 min using a 0.5-duty
      cycle (1 s contraction, 1 s rest). At 5, 20, 40, and 60 min, exercise was
      interrupted for 3 min, and the maximum positive rate of force development
      (+dF/dtmax) and maximal twitch force (Pt) were measured in maximal twitch
      contractions at 0, 1, 2, and 3 min of rest (R0, R1, R2, R3); they were also
      measured at 15 min of recovery following the entire 60-min exercise period. These
      measures were compared with pre-exercise (PRE) as an indicator of potentiation.
      Force at low frequency (10 Hz) was also measured at R0, R1, R2, and R3, and at 15
      min of recovery, while force at high frequency (100 Hz) was measured only at R0
      and R3 and in recovery. Voluntary exercise increased twitch +dF/dtmax at R0
      following 5, 20, 40, and 60 min of exercise, from 2553 +/- 150 N/s at PRE to 39%,
      41%, 42%, and 36% above PRE, respectively (P<0.005). Twitch +dF/dtmax decayed at
      brief rest (R3) following 20, 40, and 60 min of exercise (P<0.05). Pt at R0
      following 5 and 20 min of exercise was above that at PRE (P<0.05), indicating
      that during the early phase of moderate-intensity repetitive exercise,
      potentiation occurs in the relative absence of LFF. At 40 and 60 min of exercise,
      Pt at R0 was unchanged from PRE. The LFF (10 Hz) induced by the protocol was
      evident at 40 and 60 min (R0-R3; P<0.05) and at 15 min following exercise
      (P<0.05). High-frequency force was not significantly compromised by the protocol.
      Since twitch force was maintained, these results suggest that as exercise
      progresses, LFF develops, which can be compensated for by potentiation.

PMID- 14719028
TI  - Dependence of cyclopiazonic-acid-induced muscle contractures on extracellular
      Ca2+.
AB  - Inhibition of Ca2+ uptake by the sarcoplasmic reticulum decreases cytosolic Ca2+
      clearance and also triggers Ca2+ influx in response to Ca2+ store depletion. The
      role of extracellular Ca2+ in the contractures evoked by cyclo-piazonic acid
      (CPA) and thapsigargin (TG), Ca2+ pump inhibitors, was assessed in mouse
      diaphragm. At 3-100 microM, CPA elicited a rapid-onset contracture followed by a
      large elevation of muscle tone, which corresponded temporally to the monophasic
      slow contracture evoked by TG (1-30 microM). Irrespective of the differences in
      profiles, contractures were prevented and inhibited by the removal of
      extracellular Ca2+, but not by nicardipine and SK&F96365, blockers of voltage
      gated (L-type) and receptor-operated Ca2+ channels. Mn2+ and Ni2+ preferentially
      depressed the fast-phase contracture, whereas long-term pretreatment with
      LY294002, U73122, and 2-aminoethoxydiphenylborance, inhibitors of
      phosphatidylinositol kinase, phospholipase C, and inositol trisphosphate
      receptors, suppressed the slow-phase contracture. When contracture was inhibited,
      the twitch response remained augmented and prolonged by CPA and TG, indicating
      that the inhibition was not due to malfunction of the contractile apparatus. For
      preparations incubated in Ca2+-free medium containing CPA, a monophasic fast
      upstroke of muscle tone developed as extracellular Ca2+ was restored. The results
      suggest that the bimodal contracture induced by CPA is mediated by the
      recruitment of distinct Mn2+- and U73122-sensitive Ca2+ entries. The ongoing two
      component Ca2+ entries might merge if the muscle preparation was preconditioned
      with CPA in Ca2+-free medium to deplete cellular Ca2+ stores.

PMID- 14719029
TI  - Evaluation of the effect of gamma rays on the venom of Vipera lebetina by
      biochemical study.
AB  - Snake bites represent a serious public health problem in many areas of the world.
      In Algeria, two widespread snakes are Vipera lebetina and Cerastes cerastes.
      Vipera lebetina venom causes local hemorrhage and necrosis, and it may lead to
      permanent limb loss. The principal causes of mortality after snakebites are acute
      renal failure and hemorrhage, which occur not only locally, at the site of the
      bite, but also systemically, contributing to the cardiovascular shock
      characteristic of severe envenomation. Gamma radiation has been shown to be
      effective for attenuating venom toxicity. Vipera lebetina venom was irradiated
      with two doses of gamma rays (1 and 2 kGy) from a 60Co source, and the venom's
      toxic, enzymatic, and structural properties were analyzed. Intraperitoneal
      injection of the irradiated venoms (100-500 microg/20 g mouse body mass) revealed
      a significant decrease of the toxicity. Irradiated venoms with 1 and 2 kGy doses
      were four and nine times less toxic, respectively, than the native venom. A
      biochemical characterization of in vitro enzymatic activities was performed.
      Vipera lebetina displayed in vitro caseinolytic, amidolytic, esterasic,
      coagulant, and phospholipase A2 activities. Caseinolytic, amidolytic, esterasic,
      and coagulative activities were reduced for the irradiated venoms; only
      phospholipase A2 activity was abolished in the irradiated venom with a dose of 2
      kGy. The native and irradiated venoms were separated by gel filtration and
      electrophoresis. Chromatographic and electrophoretic profiles were drastically
      changed as compared with the native venom. Vipera lebetina venom detoxified by
      gamma rays was used for active immunization, and the presence of antibody in the
      immune sera was detected by ELISA. The immunogenic properties were preserved and
      the antisera obtained with the irradiated venoms could cross-react. Antisera were
      able to neutralize the toxic effect of V. lebetina native venom. These results
      indicate that irradiation of V. lebetina venom with a dose of 2 kGy can promote a
      significant detoxification, keeping the immunological properties intact.

PMID- 14719030
TI  - Effect of gamma irradiation on toxicity and immunogenicity of Androctonus
      australis hector venom.
AB  - An investigation was made of the radiosensitivity of the toxic and immunological
      properties of Androctonus australis hector venom. This venom was irradiated with
      two doses of gamma rays (1 and 2 kGy) from a 60Co source. The results showed that
      venom toxicity was abolished for the two radiation doses (1 and 2 kGy) with,
      respectively, 10 and 25 times its initial LD50 value. However, irradiated venoms
      were immunogenic, and the antibodies elicited by them were able to recognize the
      native venom by enzyme-linked immunosorbent assay. Antisera raised against these
      toxoids (1 and 2 kGy) had a higher neutralizing capacity and immunoreactivity
      against all components of native venom than did the antiserum produced against
      the native venom. The antiserum of rabbits immunized with 2-kGy-irradiated venom
      was more efficient than 1-kGy-irradiated toxoid antiserum. Indeed, in vivo
      protection assays showed that the mice immunized with 2-kGy-irradiated venom
      resisted lethal doses (i.p.) of A. australis hector venom.

PMID- 14719031
TI  - Effects of 60Co gamma radiation on toxicity and hemorrhagic, myonecrotic, and
      edema-forming activities of Cerastes cerastes venom.
AB  - Antisera are used as effective antidotes against the local effects of snake
      bites. To improve antisera production and extend the life of surrogates used to
      produce antibodies, the chronic effects of venom toxicity must be reduced. The
      present study evaluated the effectiveness of gamma irradiation to reduce the
      local effects associated with viperid snake bites by evaluating in NMRI mice the
      toxicity and edematic, hemorrhagic, and myonecrotic activities of native and
      irradiated Cerastes cerastes venoms. These results indicated that the toxicity of
      irradiated venoms (1 and 2 kGy) decreased as compared with that of native venom.
      The edematic and hemorrhagic activities were also reduced in the detoxified
      samples, particularly with the 2-kGy radiation dose. Furthermore, the creatine
      phosphokinase (CPK) activity was significantly increased in the serum and
      decreased in the myocardium after envenomation with native venom, but no
      significant enzymatic changes were observed in mice envenomated with irradiated
      venom. Histopathologic evaluation showed that native venom caused severe
      degenerative changes in the myocardium. In the case of 2-kGy-irradiated venom, no
      tissue alterations were observed. These results indicate that irradiation of
      venom with a 2-kGy dose may offer an effective method for reducing the chronic
      toxic effects of venom in immunized animals.

PMID- 14719032
TI  - Thyrotropin and iodide regulate sulfate concentration in thyroid cells.
      Relationship to thyroglobulin sulfation.
AB  - Thyroglobulin (Tg), the thyroid hormone precursor, is sulfated both on tyrosines
      and on carbohydrates. We showed recently that sulfated tyrosines were involved in
      thyroid hormone synthesis. Moreover, we also reported that Tg sulfation is
      downregulated by thyrotropin (TSH), especially on tyrosines. This control may
      occur at each step in the sulfation process. In this paper, we studied the
      regulation of the concentration of cytosolic inorganic sulfate, the first
      substrate, in porcine thyroid cells stimulated by TSH with or without iodide. The
      amounts of cytosolic sulfate and the cytosolic volumes measured showed that the
      sulfate concentration depends only on cytosolic volume changes in response to TSH
      and iodide treatment. After the cells were labelled with [35S]-sulfate, the
      specific radioactivity (SRA) of cytosolic sulfate was determined. When cells were
      treated with only TSH, the concentration and SRA of cytosolic sulfate decreased
      by 30%, and by about 15% when cells were incubated with both TSH and iodide. TSH
      decreased more conspicuously the rate of [35S]-sulfate incorporation into Tg (by
      57% without iodide, by 43% with iodide) than the concentration and SRA of
      cytosolic sulfate, while iodide altered these parameters to the same extent
      (15%). These findings suggest that TSH regulates other steps in the sulfation
      process, such as specific substrate and enzyme levels, while iodide controls
      mainly the sulfate concentration.

PMID- 14719033
TI  - Comparative study of perturbations of peripheral markers in different stressors
      in rats.
AB  - Stress has been implicated in the etiopathogenesis of several diseases. In the
      present study, the effects of acute (AS), chronic (CS), and chronic unpredictable
      stress (CUS) were studied on the ulcer index, adrenal gland mass, and biochemical
      and hormonal changes in rats. The stress was provided in the form of
      immobilization-immobilization for 150 min, once only, and for 10 consecutive days
      in CS and CUS. In CUS, animals received variable unpredictable stressors.
      Immediately after stress, animals were decapitated, blood was collected, and
      plasma was separated for the estimation of plasma glucose, triglyceride,
      cholesterol, creatine kinase (CK), corticosterone, and insulin. The adrenal gland
      and stomach were also dissected for mass and ulcer scoring, respectively. AS
      significantly increased the ulcer index, plasma glucose, CK, corticosterone, and
      insulin. CS and CUS significantly increased the ulcer index, adrenal gland mass,
      and corticosterone. In CS, a significant decrease in plasma triglyceride and
      cholesterol levels was found, but in CUS only cholesterol was decreased
      significantly. High CK activity and hyperglycemia maintain the energy demands of
      metabolism, and elevated corticosterone desensitizes the insulin receptor in AS.
      In CS and CUS, prolonged elevation of corticosterone shifts metabolism to
      utilization of lipids as a secondary substrate by gluconeogenesis. From our
      experiment, it is clear that AS causes maximum activation of energy metabolism,
      which becomes specific after habituation in prolonged CS. These biochemical
      manipulations in the body by using different types of stressors are good markers
      that can be of great use to understand, target, and manage stress-induced
      etiologies.

PMID- 14719034
TI  - Reactivity of isolated human chorionic vessels: analysis of some influencing
      variables.
AB  - The aim of the study was to determine whether 24 h of cold storage of samples,
      mode of delivery, and gestational age influenced in vitro human chorionic
      vascular reactivity (35 arteries and 34 veins). The following groups were
      compared: (i) fresh versus 24-h cold-stored (4 degrees C in Krebs-Henseleit
      solution) chorionic vascular rings from normal term placentas, (ii) fresh
      chorionic vascular rings from normal term placentas obtained after vaginal
      delivery versus those obtained after elective caesarean section, and (iii) fresh
      chorionic vascular rings from normal term placentas versus those obtained from
      preterm deliveries. Isometric recording of the concentration-response curve to
      KCl (5-120 mM) was assessed in each group. In vitro human chorionic vascular
      reactivity was influenced negatively by the 24-h cold storage of samples, with
      only 30% of stored samples being weakly reactive to KCl. Human chorionic vascular
      reactivity to KCl was unaffected by the mode of delivery. However, the response
      to KCl was gestational-age dependent. Thus, preterm vascular rings exhibited a
      significantly (P<0.05) decreased response (Emax=9.8 +/- 0.0 mN; EC50=26.0 +/- 1.3
      mM) compared with term samples (Emax=21.6 +/- 2 mN; EC50=13.9 +/- 1.6 mM). In
      conclusion, this study provides evidence that fresh term vascular rings are the
      tissues of choice for studying human chorionic vascular reactivity.

PMID- 14719035
TI  - Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1
      and glucagon-like peptide-2.
AB  - The proglucagon-derived peptide family consists of three highly related peptides,
      glucagon and the glucagon-like peptides GLP-1 and GLP-2. Although the biological
      activity of glucagon as a counter-regulatory hormone has been known for almost a
      century, studies conducted over the past decade have now also elucidated
      important roles for GLP-1 as an antidiabetic hormone, and for GLP-2 as a
      stimulator of intestinal growth. In contrast to pancreatic glucagon, the GLPs are
      synthesized in the intestinal epithelial L cells, where they are subject to the
      influences of luminal nutrients, as well as to a variety of neuroendocrine
      inputs. In this review, we will focus on the complex integrative mechanisms that
      regulate the secretion of these peptides from L cells, including both direct and
      indirect regulation by ingested nutrients.

PMID- 14719036
TI  - Endothelium-derived reactive oxygen species: their relationship to endothelium
      dependent hyperpolarization and vascular tone.
AB  - Opinions on the role of reactive oxygen species (ROS) in the vasculature have
      shifted in recent years, such that they are no longer merely regarded as
      indicators of cellular damage or byproducts of metabolism--they may also be
      putative mediators of physiological functions. Hydrogen peroxide (H2O2), in
      particular, can initiate vascular myocyte proliferation (and, incongruously,
      apoptosis), hyperplasia, cell adhesion, migration, and the regulation of smooth
      muscle tone. Endothelial cells express enzymes that produce ROS in response to
      various stimuli, and H2O2 is a potent relaxant of vascular smooth muscle. H2O2
      itself can mediate endothelium-dependent relaxations in some vascular beds.
      Although nitric oxide (NO) is well recognized as an endothelium-derived dilator,
      it is also well established, particularly in the microvasculature, that another
      factor, endothelium-derived hyperpolarizing factor (EDHF), is a significant
      determinant of vasodilatory tone. This review primarily focuses on the hypothesis
      that H2O2 is an EDHF in resistance arteries. Putative endothelial sources of H2O2
      and the effects of H2O2 on potassium channels, calcium homeostasis, and vascular
      smooth muscle tone are discussed. Furthermore, given the perception that ROS can
      more likely elicit cytotoxic effects than perform signalling functions, the
      arguments for and against H2O2 being an endogenous vasodilator are assessed.

PMID- 14719037
TI  - Cellular and humoral responses to collagen-polyvinylpyrrolidone administered
      during short and long periods in humans.
AB  - Collagen, particularly type I, and its related derivatives have been extensively
      employed in many areas of pharmacology. The present study was performed to
      determine the safety of collagen-polyvinylpyrrolidone (collagen-PVP) by in vitro
      and in vivo studies. Sera and peripheral blood cells from healthy donors without
      treatment and patients treated with collagen-PVP were evaluated. We observed that
      the biodrug does not stimulate lymphoproliferation or DNA damage in vitro, nor
      does it induce human anti-porcine type I collagen or anti-collagen-PVP antibodies
      in vivo. Furthermore, no hepatic or renal metabolic dysfunctions were observed
      when collagen-PVP was administered by intradermal or intramuscular routes in
      short- or long-term treatments. In conclusion, the present work shows that no
      cellular damage or immunological adverse effects (cellular and humoral) occurred
      during collagen-PVP treatment, even after more than 400 weeks of consecutive
      administrations.

PMID- 14719038
TI  - Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive
      rats: role of sympathoexcitation.
AB  - Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR).
      This study examined the relative contribution of the renin-angiotensin system and
      the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous
      injections of insulin were initiated either before short-term angiotensin
      converting enzyme inhibition with captopril or after lifetime captopril
      treatment. Insulin treatment resulted in significant increases in mean arterial
      pressure and heart rate and captopril treatment lowered arterial pressure, but
      captopril did not lower arterial pressure more in the insulin-treated compared
      with control rats. To test the contribution of the sympathetic nervous system to
      this form of hypertension, each rat was intravenously infused with either a
      ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic
      receptor agonist (i.e., clonidine). Administration of either agent largely
      eliminated the differences in mean arterial pressure and heart rate between the
      insulin-treated and saline-treated SHR, irrespective of captopril treatment.
      These data indicate that in SHR, the ability of insulin to increase blood
      pressure is closely related to sympathoexcitation, which is unresponsive to
      blockade of angiotensin-converting enzyme.

PMID- 14719039
TI  - Dietary restriction and fibre supplementation: oxidative stress and metabolic
      shifting for cardiac health.
AB  - Dietary modification ought to be the first line of strategy in prevention of the
      development of cardiac disease. The purpose of this study was to investigate
      whether dietary restriction, dietary-fibre-enriched diet, and their interactions
      might affect antioxidant capacity and oxidative stress in cardiac tissue. Male
      Wistar rats (180-200 g; n=10) were divided into four groups: control ad libitum
      diet (C), 50% restricted diet (DR), fed with fibre-enriched diet (F), and 50%
      restricted fibre-enriched diet (DR-F). After 35 days of the treatments, F, DR,
      and DR-F rats showed low cholesterol, LDL-cholesterol, and triacylglycerol, and
      high HDL-cholesterol in serum. The DR, DR-F, and F groups had decreased
      myocardial lipoperoxide and lipid hydroperoxide. The DR-F and F treatments
      increased superoxide dismutase and glutatione peroxidase (GSH-Px). The DR
      treatment increased GSH-Px and catalase activities. Dietary fibre beneficial
      effects were related to metabolic alterations. The F and DR-F groups showed high
      cardiac glycogen and low lactate dehydrogenase/citrate synthase ratios,
      indicating diminished anaerobic and elevated aerobic myocardial metabolism in
      these animals. There was no synergistic effect between dietary restriction and
      dietary fibre addition, since no differences were observed in markers of
      oxidative stress in the F and DR-F groups. Dietary fibre supplementation, rather
      than energy intake and dietary restriction, appears to be the main process
      retarding oxidative stress in cardiac tissue.

PMID- 14719040
TI  - Chronic glucose-lowering effects of rosiglitazone and
      bis(ethylmaltolato)oxovanadium(IV) in ZDF rats.
AB  - The aim of this study was to determine if there was a synergistic or additive
      effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium
      compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and
      insulin levels following chronic oral administration to Zucker diabetic fatty
      (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1,
      6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 micromol/kg) were
      selected to produce a glucose-lowering effect in 30% (ED30) of animals. Both
      drugs were administered daily by oral gavage as suspensions in 1%
      carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume
      administered to all rats was 5 mL/(kg.day). The combination of BEOV and ROS was
      effective in lowering plasma glucose levels to <9 mmol/L in 60% of fatty animals
      as compared with 30% for BEOV and 10% for ROS alone. The age-dependent decrease
      in plasma insulin levels associated with beta-cell failure in the ZDF rats did
      not occur in the BEOV-treated fatty groups. There was no effect of any treatment
      on body weight; however, there was a significant reduction in both food and fluid
      intake in fatty groups treated with BEOV. There were no overt signs of toxicity
      and no mortality in this study. Both BEOV and ROS were effective in lowering
      plasma glucose levels, as stated above, and there was at least an additive effect
      when BEOV and ROS were used in combination.

PMID- 14719041
TI  - Attenuation of the serotonin-induced increase in intracellular calcium in rat
      aortic smooth muscle cells by sarpogrelate.
AB  - Although serotonin (5-HT) induced proliferation of vascular smooth muscle cells
      is considered to involve changes in intracellular Ca2+ ([Ca2+]i), the mechanism
      of Ca2+ mobilization by 5-HT is not well defined. In this study, we examined the
      effect of 5-HT on rat aortic smooth muscle cells (RASMCs) by Fura-2
      microfluorometry for [Ca2+]i measurements. 5-HT was observed to increase the
      [Ca2+]i in a concentration- and time-dependent manner. This action of 5-HT was
      dependent upon the extracellular concentration of Ca2+ ([Ca2+]e) and was
      inhibited by both Ca2+ channel antagonists (verapamil and diltiazem) and
      inhibitors of sarcoplasmic reticular Ca2+ pumps (thapsigargin and cyclopia zonic
      acid). The 5-HT-induced increase in [Ca2+]i was blocked by sarpogrelate, a 5-HT2A
      receptor antagonist, but not by different agents known to block other receptor
      sites. 5-HT-receptor antagonists such as ketanserin, cinanserin, and mianserin,
      unlike methysergide, were also found to inhibit the 5-HT-induced Ca2+
      mobilization, but these agents were less effective in comparison to sarpogrelate.
      On the other hand, the increase in [Ca2+]i in RASMCs by ATP, angiotensin II,
      endothelin-1, or phorbol ester was not affected by sarpogrelate. These results
      indicate that Ca2+ mobilization in RASMCs by 5-HT is mediated through the
      activation of 5-HT2A receptors and support the view that the 5-HT-induced
      increase in [Ca2+]i involves both the extracellular and intracellular sources of
      Ca2+.

PMID- 14719042
TI  - Effects of statins on myocardial and coronary artery response to ischemia
      reperfusion.
AB  - This study tested the hypotheses that (i) lipophilic statins (atorvastatin and
      simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion,
      owing to their greater myocyte permeability, compared with a hydrophilic statin
      (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of
      isolated coronary arteries from the ischemic region. Farm pigs consumed chow
      supplemented with atorvastatin (2.5 mg.kg(-1).d(-1); n=6), pravastatin (10 (n=3)
      or 20 (n=2) mg.kg(-1).d(-1)), simvastatin (5 mg.kg(-1).d(-1); n=6), or no statin
      (control; n=6) for 3 weeks. Animals were anesthetized and instrumented to measure
      regional (% segment shortening) and global (dP/dt max) left ventricular (LV)
      function during coronary artery occlusion (10 min) and reperfusion (30 min).
      Coronary resistance (i.d. = 119 +/- 3 microm) and conductance (i.d. = 487 +/- 11
      microm) arteries were isolated from the ischemic region to measure receptor
      dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and
      endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside
      (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional
      ventricular function (atorvastatin, 24% +/- 15%; pravastatin, 36% +/- 13%;
      simvastatin, 29% +/- 13%; control, 36% +/- 13%) nor percent recovery of global LV
      cardiac function differed among groups. However, BK-induced vasorelaxation of
      coronary conductance vessels was greater (P<0.05) in statins versus controls, and
      ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting
      the potential for enhanced coronary arterial blood flow to the jeopardized
      region. In conclusion, our data suggest that ischemia-induced myocardial stunning
      is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or
      simvastatin, even though statin treatment appears to augment endothelium
      dependent vasodilation of conductance, but not resistance, vessels subjected to
      ischemia-reperfusion.

PMID- 14719043
TI  - Effects of chronic AICAR administration on the metabolic and contractile
      phenotypes of rat slow- and fast-twitch skeletal muscles.
AB  - The present study examined the effects of chronic activation of 5'-AMP-activated
      protein kinase (AMPK) on the oxidative capacity and myosin heavy chain (MHC)
      based fibre phenotype of rodent fast- and slow-twitch muscles. Sprague-Dawley
      rats received daily injections for 4 weeks of the known AMPK activator 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or vehicle
      (control). The AICAR group displayed increases in hexokinase-II (HXK-II)
      activity, expression, and phosphorylation in fast-twitch muscles (P<0.001) but
      not in the slow-twitch soleus (SOL). In the AICAR group, citrate synthase (EC
      4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35) were elevated 1.6- and
      2.1-fold (P<0.05), respectively, in fast-twitch medial gastrocnemius (MG), and by
      1.2- and 1.4-fold (P<0.05) in the slower-twitch plantaris (PLANT). No changes
      were observed in the slow-twitch SOL. In contrast, the activity of glyceraldehyde
      phosphate dehydrogenase (EC 1.2.1.12) remained unchanged in all muscles. AICAR
      treatment did not alter the MHC-based fibre type composition in fast- or slow
      twitch muscles, as determined by immunohistochemical and electrophoretic
      analytical methods or by RT-PCR. We conclude that chronic activation of AMPK
      mimics the metabolic changes associated with chronic exercise training (increased
      oxidative capacity) in the fast-twitch MG and PLANT, but does not coordinately
      alter MHC isoform content or mRNA expression.

PMID- 14719045
TI  - Does lithium save lives?

PMID- 14719046
TI  - The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of
      interferon-alpha-induced depression.
AB  - The mechanisms by which administration of interferon-alpha induces
      neuropsychiatric side effects, such as depressive symptoms and changes in
      cognitive function, are not clear as yet. Direct influence on serotonergic
      neurotransmission may contribute to these side effects. In addition, the enzyme
      indoleamine 2,3-dioxygenase (IDO), which converts tryptophan into kynurenine, may
      play an important role, first, because IDO activation leads to reduced levels of
      tryptophan, the precursor of serotonin (5-HT), and thus to reduced central 5-HT
      synthesis. Second, kynurenine metabolites such as 3-hydroxy-kynurenine (3-OH-KYN)
      and quinolinic acid (QUIN) have toxic effects on brain function. 3-OH-KYN is able
      to produce oxidative stress by increasing the production of reactive oxygen
      species (ROS), and QUIN may produce overstimulation of hippocampal N-methyl-D
      aspartate (NMDA) receptors, which leads to apoptosis and hippocampal atrophy.
      Both ROS overproduction and hippocampal atrophy caused by NMDA overstimulation
      have been associated with depression.

PMID- 14719047
TI  - Eating disorders and the serotonin connection: state, trait and developmental
      effects.
AB  - Alterations in brain serotonin (5-hydroxytryptamine [5-HT]) function are thought
      to contribute to diverse aspects of eating disorders, including binge eating,
      perfectionism, impulsivity and mood-regulation problems. In addition, 5-HT
      anomalies in individuals with eating disorders are believed to have multiple
      determinants associated with secondary (state-related) effects of their
      nutritional status, hereditary effects (related to such trait variations as
      impulsivity or perfectionism) and, possibly, long-term neurobiologic sequelae of
      developmental stressors (such as childhood abuse). On the strength of the
      available neurobiologic and genetic data, this paper presents the idea that 5-HT
      variations in those with eating disorders represent (1) a structured
      coaggregation of biologic, psychologic and social influences and (2) converging
      state, trait and developmental effects. Data are taken to support a
      multidimensional model of 5-HT function in eating disorders that, it is argued,
      can serve as a prototype for etiologic modelling, diagnostic classification and
      clinical decision-making bearing not only upon eating disorders but also upon
      other psychiatric disturbances.

PMID- 14719048
TI  - Immediate effects of risperidone on cerebral activity in healthy subjects: a
      comparison with subjects with first-episode schizophrenia.
AB  - OBJECTIVE: To test the hypothesis that administration of risperidone to healthy
      subjects produces reductions in metabolism in the frontal cortex similar to those
      produced by administration of risperidone to patients experiencing a first
      episode of schizophrenia. METHODS: Positron emission tomography was used to
      measure the changes in regional metabolism produced by a single 2-mg dose of
      risperidone and by placebo, administered under randomized, double-blind
      conditions, in 9 healthy subjects. Conjunction analysis was used to identify
      those cerebral sites where changes in metabolism in the healthy subjects
      coincided with similar changes in metabolism observed in patients with
      schizophrenia. RESULTS: Compared with placebo, risperidone produced reductions in
      metabolism in the left lateral frontal cortex and right medial frontal cortex in
      healthy subjects. Conjunction analysis revealed that these changes occurred at
      locations similar to the loci of change produced by risperidone in patients with
      schizophrenia. CONCLUSION: Because the reduction in metabolism in the medial
      frontal cortex produced by risperidone is associated with alleviation of positive
      symptoms in patients with schizophrenia, the observation of a reduction in
      metabolism at a similar site in healthy subjects supports the hypothesis that the
      antipsychotic effect of risperidone arises, at least in part, from a physiologic
      effect that occurs in both patients with schizophrenia and healthy subjects.

PMID- 14719050
TI  - The physician-scientist in Canadian psychiatry.
AB  - OBJECTIVE: The objective of the study was to determine whether physician
      scientists in psychiatry in Canada are in decline, as was reported for medicine
      overall during the 1990s in the United States. DESIGN: Federal databases were
      searched to study grant applications in the area of mental health submitted by
      physician-scientists compared with PhD-scientists for the period 1985-2001. A
      survey of Canadian Residency Training Program Directors was carried out for the
      graduating class of 2000. SETTING: The Canadian publicly funded university
      system. PARTICIPANTS: Applicants to the Medical Research Council of Canada and
      its successor, the Canadian Institutes of Health Research, for operating grant
      support and Residency Training Program Directors. INTERVENTIONS: None. OUTCOME
      MEASURES: Comparison over time between MD and PhD applicants regarding the number
      of grant applications submitted, the proportion of applications funded and the
      number of new applications submitted, with separation of applications submitted
      to a predominantly "biomedical" peer review committee and to a predominantly
      "clinical research" peer review committee. The survey obtained information about
      a number of variables related to research training. RESULTS: The situation for
      physician-scientists in psychiatry in Canada appeared remarkably similar to
      general findings in US studies. Relative to PhD applicants, fewer grant proposals
      were being made by physicians (paired t16 = 7.08, p < 0.001) and, in consequence,
      fewer proposals were funded. The proportion of proposals funded was similar for
      MD and PhD applicants (paired t16 = 0.27, p = 0.79). Grant applications made to
      the predominantly biomedical committee were more likely to be funded than
      applications to the committee with an orientation toward clinical research
      (paired t7 = 5.53, p < 0.001). Applications by PhD-scientists to the biomedical
      committee showed the largest increase over time and were the most successful.
      From the survey of graduating classes, close to one-third of residents had
      authored or co-authored a publication during residency. Only 7% were proceeding
      to research fellowship training. The remuneration available for fellowship
      training was about one-third of what graduating classmates could expect to earn
      in the first year of practice. CONCLUSIONS: Quantitative data indicate that
      physician-scientists in psychiatry in Canada are experiencing the same pressures
      and challenges as physician-scientists in the United States. A plan of action
      tailored to the needs of the psychiatric community in Canada needs to be
      developed.

PMID- 14719049
TI  - Heroin and cocaine co-use in a group of injection drug users in Montreal.
AB  - OBJECTIVE: To describe the pattern of co-use of heroin and cocaine in individuals
      who were not receiving methadone maintenance treatment. DESIGN: Structured
      interviews. SETTING: Community hospital. PARTICIPANTS: Individuals (n = 1111)
      selected from a cohort of out-of-treatment injection drug users in Montreal, Que.
      OUTCOME MEASURE: Frequency (injections per day) and quantity (number of days of
      use) of heroin, cocaine and speedball (the simultaneous administration of heroin
      and cocaine) use reported in the month preceding the interview. RESULTS: About
      50% of the sample reported using only cocaine intravenously (C group), about 8%
      reported using only heroin (H group) intravenously and about 15% reported using
      both heroin and cocaine (HC group) intravenously. Reported cocaine consumption
      was similar in the HC and C groups. Heroin was used on fewer days by the HC than
      by the H group, but the number of injections per day was similar. Speedball use,
      which was quantified independently from heroin and cocaine use, was reported
      almost exclusively by the HC group, and speedball was used less often than either
      heroin or cocaine alone. Finally, a similar proportion of individuals in the C
      and the HC groups consumed alcohol in the 24 hours preceding the interview, but a
      larger proportion of individuals in the HC group reported the use of marijuana.
      CONCLUSION: In a cohort of injection drug users in Montreal, cocaine was the most
      prevalent illicit drug. Furthermore, about 70% of the heroin users also injected
      cocaine, but not in the form of speedball. Thus, the sequential co-use of heroin
      and cocaine is highly prevalent in Montreal and deserves particular clinical
      attention.

PMID- 14719051
TI  - Olanzapine in the treatment of pervasive developmental disorders: a case series
      analysis.
AB  - Controlling the symptoms that are characteristic of patients with pervasive
      developmental disorders is often challenging. We report on the safety and
      efficacy of olanzapine in the treatment of 7 patients with pervasive
      developmental disorders. The patients were all male and ranged in age from 8 to
      52 years. They received olanzapine doses of 5-10 mg/d along with their various
      other drug regimens. Patients were monitored and evaluated for a mean duration of
      17.7 (range 12-26) months while on olanzapine therapy. Very few side effects were
      observed during treatment. All patients showed clinically significant improvement
      on the Clinical Global Impressions scale, as well as an improved score as
      measured by the Global Assessment of Functioning scale. Our observations support
      the use of long-term olanzapine therapy for symptom control in patients with
      pervasive developmental disorders.

PMID- 14719052
TI  - Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor
      celecoxib.
AB  - Higher cyclooxygenase-2 (COX-2) expression is clinically associated with more
      aggressive gliomas and is a strong predictor of poor survival. To determine
      whether oral administration of a COX-2-specific inhibitor can inhibit glial
      tumors, we analyzed the effect of celecoxib on the growth of 9L rat gliosarcoma
      cells that were orthotopically transplanted into rat brains. Oral administration
      of celecoxib beginning 1 day after implantation of 5 x 10(4) 9L rat gliosarcoma
      cells into rat brain reduced the incidence and size of tumors significantly.
      Immunohistochemical analysis of implanted gliosarcoma cells from rats treated
      with celecoxib showed lower levels of phospho-Akt, phospho-EGFR, Bcl-2, and Bcl
      XL expression compared with untreated tumor cells. Gliosarcoma cells from treated
      rats had significantly more TUNEL- and caspase-3-positive cells and fewer PCNA
      positive cells. These results demonstrate that selective COX-2 inhibitors may be
      useful as adjuvants and/or therapeutic agents to treat gliomas overexpressing COX
      2.

PMID- 14719053
TI  - Pathological features and surgical outcome of pancreaticobiliary maljunction
      without dilatation of the extrahepatic bile duct.
AB  - In cases of pancreaticobiliary maljunction without dilatation of the extrahepatic
      bile duct (undilated PBM), preventive cholecystectomy is performed because there
      is a high incidence of gallbladder cancer as compared to cases of PBM with
      dilatation of the extrahepatic bile duct (dilated PBM). However, it is still
      controversial whether resection of the extrahepatic bile duct should also be
      performed in patients with undilated PBM. Accordingly, we analyzed pathological
      findings, postoperative complications and a long-term prognosis in 19 patients
      with undilated PBM to clarify the possibility of the bile duct cancer. In
      undilated PBM, hyperplasia was significantly recognized in the gallbladder as
      compared to the bile duct (p=0.0238), while no significant differences were found
      in other epithelium. Atypical epithelium and hyperplasia in gallbladder mucosa of
      undilated PBM were significantly recognized as compared to cases of pancreas or
      biliary tract cancer without PBM (p=0.0035, p=0.0019, respectively), while no
      significant differences were recognized in any kind of epithelium of the bile
      duct. In 14 cases of undilated PBM with preservation of the extrahepatic bile
      duct, the postoperative observation period was from 1 year and 5 months to 18
      years and 10 months (mean: 8.3 years). One of the 5 patients with gallbladder
      cancer died 2 years and 6 months after surgery due to the cancer recurrence,
      while the remaining 13 patients had no complications such as liver dysfunction,
      cholangitis or remnant bile duct cancer, and the patients have survived in good
      health. These findings indicate that preventive bile duct resection is not
      necessary in patients with undilated PBM.

PMID- 14719054
TI  - Prognostic significance of localized p27Kip1 and potential role of Jab1/CSN5 in
      pancreatic cancer.
AB  - p27Kip1 belongs to the family of small polypeptides collectively termed cyclin
      dependent kinase inhibitors, which negatively regulate the cell cycle
      progression. In various human cancers, the reduced p27Kip1 expression correlates
      well with poor prognosis. Recently, Jab1/CSN5, the fifth component of the COP9
      signalosome complex, was found to specifically translocate p27Kip1 from the
      nucleus to the cytoplasm, and reduce the protein level of p27Kip1 by accelerating
      its degradation. In this study, we investigated the expression of p27Kip1 and
      Jab1 in 61 cases with pancreatic ductal adenocarcinoma. The p27Kip1 expression
      was positive in 41% (25/61) of the tumors. Of the 25 positive tumors, 12 cases
      had p27Kip1 positive expression mainly in the nucleus of the tumor cells, while
      13 cases had p27Kip1 in the cytoplasm as well as in the nucleus. Among a variety
      of clinicopathological factors, only tumor status was inversely correlated with
      p27Kip1 expression (p=0.019). The Jab1 expression was detected both in the
      nucleus and the cytoplasm in almost all pancreatic cancer cells. The intensity of
      Jab1 expression in tumor cells, especially in the cytoplasm, was much stronger
      than in normal pancreatic ductal epithelial cells. The patients with positive
      p27Kip1 expression had significantly better prognosis than ones with negative
      p27Kip1 expression (p=0.008). Furthermore, 12 patients with exclusively nuclear
      p27Kip1 expression, but not 13 patients with both nuclear and cytoplasmic p27Kip1
      expression, had significantly better prognosis than 36 patients with negative
      p27Kip1 expression (p=0.009). In multivariate survival analysis, localized
      p27Kip1 expression was an independent prognostic factor (p=0.016). The results of
      our study suggested that the mislocalization as well as the downregulation of
      p27Kip1 had significant prognostic value in pancreatic cancer and that Jab1 might
      play an important role in carcinogenesis of pancreatic cancer. Cell cycle control
      targeting p27Kip1 might be a promising future therapeutic modality against
      pancreatic cancer.

PMID- 14719055
TI  - Imprint cytologic features of pulmonary large cell neuroendocrine carcinoma:
      Comparison with classic large cell carcinoma.
AB  - The World Health Organization (WHO) categorized large cell neuroendocrine
      carcinoma (LCNEC) as a variant of large cell carcinoma in 1999. However,
      cytologic features of these tumors have not yet been adequately characterized.
      The cytologic features of 24 cases of LCNEC were analyzed and compared to the
      features of 16 cases of classic large cell carcinoma (CLCC). Giant cells,
      neutrophils and cytophagocytosis were observed more frequently in CLCC than in
      LCNEC (p<0.05), whereas the unclear border of tumor cells was seen more
      frequently in LCNEC (p<0.05). The presence of nuclear atypia, such as
      anisokaryosis, nuclear budding, irregularity of nuclear margins, and
      multinucleation (having three or more nuclei), was observed less frequently in
      LCNEC. Characteristic arrangements of tumor cells, such as rosette formation, and
      palisading, were observed only in LCNEC cases. In morphometric studies, the
      nuclear areas, cytoplasmic areas, and nuclear rotundity ratios were significantly
      higher in CLCC cells than in LCNEC cells (p<0.05). However, N/C ratios were
      significantly higher in LCNEC than in CLCC. LCNEC cells have less nuclear atypia
      than CLCC cells, and have the characteristic arrangements of tumor cells, such as
      palisading and rosette. It is possible to preoperatively differentiate LCNEC from
      CLCC by careful cytologic characterization.

PMID- 14719056
TI  - Induction of apoptosis by lupeol isolated from mokumen (Gossampinus malabarica L.
      Merr) in human promyelotic leukemia HL-60 cells.
AB  - We have investigated the effect of lupeol (lup-20(29)-ene-3beta-ene-3-ol)
      isolated from mokumen (Gossampinus malabarica L. Merr) on DNA of human
      promyelotic HL-60 leukemia cells. Induction of apoptosis by lupeol was observed
      in human leukemia HL-60 cells. Morphological change showing apoptotic bodies was
      observed in the HL-60 cells treated with lupeol. The fragmentation of DNA by
      lupeol to oligonucleosomal-sized fragments that is a characteristic of apoptosis
      was observed to be concentration- and time-dependent in the HL-60 cells. Flow
      cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were
      increased to 28.5, 42.0 and 70.9% after a 3-day treatment with 75, 100 and 150
      micro M lupeol, respectively. The data of the present study show that the
      suppression by lupeol of growth of the HL-60 cells results from the induction of
      apoptosis by this compound.

PMID- 14719057
TI  - Endobronchial ultrasound using a new convex probe: a preliminary study on
      surgically resected specimens.
AB  - The radial endobronchial ultrasound (EBUS) probe is conventionally inserted
      through the working channel of the flexible bronchoscope and limits
      interventional diagnostics and therapeutics under direct ultrasound control. The
      aim of this study was to assess the new convex probe EBUS (CP-EBUS) in the
      visualization of the hilar lymph nodes in surgically resected specimens and
      explore its feasibility to perform transbronchial needle aspiration (TBNA) under
      direct EBUS guidance prior to its clinical use. Fourteen surgically resected
      specimens from lung cancer (n=12) and metastatic lung cancer (n=2) patients were
      included in the study. The resected specimens included eight right upper lobes,
      one right middle lobe, and five left lower lobes. The EBUS examination was
      performed with a flexible bronchoscope equipped with a 7.5 MHz convex probe (CP)
      that scans parallel to the insertion direction of the bronchoscope. The
      appearance of the hilar lymph nodes using this CP-EBUS was noted. The size of
      hilar lymph nodes was measured at CP-EBUS and compared with the actual size of
      the lymph nodes, which was measured with a Vernier's caliper. Hilar lymph nodes
      could be clearly visualized with CP-EBUS. There was a good correlation between
      the actual size of the lymph node and that measured using CP-EBUS (R(2)=0.950). A
      dedicated transbronchial aspiration needle could be inserted into the hilar lymph
      node under direct ultrasonic control. There is a possibility in the
      underestimation of the size of large lymph nodes due to the scanning nature of
      the convex probe. The CP-EBUS was successfully used to visualize the hilar lymph
      node and perform TBNA in surgical resected lung specimens. This technique has an
      excellent potential to perform direct ultrasound guided TBNA of mediastinal and
      hilar lymph nodes.

PMID- 14719058
TI  - In situ human telomerase reverse transcriptase expression pattern in normal and
      neoplastic ovarian tissues.
AB  - Telomerase is a ribonuclear protein reverse transcriptase that maintains telomere
      length in eukaryotic cells. Activation of telomerase has been implicated in human
      cellular immortalization and carcinogenesis. Telomerase activity in ovarian
      neoplasm has been studied using polymerase chain reaction (PCR)-based methods and
      shown to be correlated with malignancy. However, we believe those results must be
      interpreted with caution because such studies used a heterogeneous mix of cells,
      including normal cell type known to express telomerase when activated. The
      present study used in situ hybridization that allows determination of the type of
      cells expressing telomerase, as well as the intensity of that expression, in
      ovarian neoplasms. A total of 75 specimens were studied. Epithelial telomerase
      reverse transcriptase mRNA expression was detected in 28 of 31 epithelial ovarian
      carcinomas, 1 of 1 malignant granulosa cell tumor, 7 of 9 serous borderline
      ovarian tumors, 11 of 11 mucinous borderline ovarian tumors, 4 of 5 serous
      cystadenofibromas, 2 of 4 serous cystadenomas, 8 of 8 mucinous cystadenomas, and
      0 of 6 normal ovaries except the corpus luteum. Telomerase expression is
      heterogeneously found in both benign and malignant epithelial tissues. We
      conclude that human telomerase reverse transcriptase mRNA expression does not
      seem to be a reliable marker for clinical use in differentiating between benign
      and malignant tumors.

PMID- 14719059
TI  - A versatile in vivo chamber angiogenesis assay for measuring anti-angiogenic
      activity in mice.
AB  - We recently described an in vivo angiogenesis assay for rats--an optimized
      Matrigel plug assay based on subcutaneously implanted chambers with fixed volume
      and shape. Here we examine the possibility of switching the host animal from rat
      to mouse, thereby reducing the requirement for test compound an order of
      magnitude. The chambers consist of a plexiglas ring with a 0.2 ml volume and two
      nylon net filters. Chambers containing growth factor-reduced Matrigel
      supplemented with basic fibroblast growth factor (bFGF) were subcutaneously
      implanted in the right flank of three different strains of mice; BALB/c,
      C57BL/6J, and NMRI-nu. On day 10 post-implantation: i) each chamber was taken
      out, ii) a picture of the induced angiogenic response was taken, and iii) the
      redness of the chamber content was quantified by computer image analysis. The
      level of bFGF-induced angiogenesis in the mouse assay was lower than in the
      previously published rat assay. Importantly, the background angiogenesis in mice
      in chambers containing Matrigel alone was correspondingly decreased. Therefore, a
      more sensitive threshold for the computer image analysis was used. In all three
      strains of mice, bFGF-induced angiogenesis was significantly increased compared
      to Matrigel alone. Furthermore, the positive anti-angiogenic control compound TNP
      470 (10 mg/kg/d s.c.) completely inhibited the bFGF-induced angiogenesis. The in
      vivo chamber angiogenesis assay allows quantitative analysis of angiogenic and
      anti-angiogenic activity in mice. The model is very robust and only little
      influenced by the choice of mouse strain.

PMID- 14719060
TI  - COX-2 status in relation to tumor microvessel density and VEGF expression:
      analysis in ovarian carcinoma patients with low versus high survival rates.
AB  - Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and
      microvessel density (MVD) have been reported to be significantly related to
      carcinogenesis and to tumoral progression. The aim of the study was to analyse
      immunohistochemically the overexpression of COX-2 and VEGF, and the MVD between
      one another, and also in relation with clinical outcome in ovarian carcinoma. We
      selected 52 patients with ovarian carcinoma homogeneous by stage, type and
      histological grade, surgical and chemotherapeutic treatment. Of these, 28
      patients had died of progression of their disease within 2 years of their primary
      surgical treatment, while 24 patients were alive with no evident disease at 5
      years from the primary surgical treatment. The differences of the COX-2 status,
      the MVD and the VEGF expression in the two groups of ovarian carcinoma patients
      with low and high survival rate, respectively, were calculated according to the
      Fisher's exact test and the logistic regression. The shift in location of MVD in
      the two groups of patients was calculated according to the Wilcoxon Mann-Whitney
      test. MVD was correlated with COX-2 and VEGF overexpression (P=0.009 and P=0.003,
      respectively), COX-2 and VEGF were correlated to one another (P=0.044). In
      logistic regression analysis, COX-2, VEGF, and MVD were significant (P=0.017,
      P=0.008, P<0.0005, respectively). In the cases with low survival rate, the
      average MVD was 102, while in the cases with high survival rate the average MVD
      was 40.5 (P<0.0005). The evaluation of the COX-2, the VEGF and the MVD may give
      additional prognostic information for first-line chemotherapy and clinical
      outcome of patients with ovarian carcinoma and may encourage selection of more
      tailored therapies. Angiogenesis inhibitors or COX-inhibitors probably can have
      synergistic effects with chemotherapy.

PMID- 14719061
TI  - Angiogenic switch occurs during the precancerous stage of human esophageal
      squamous cell carcinoma.
AB  - We previously reported that vascular endothelial growth factor (VEGF) expression
      correlates with vessel density in human esophageal squamous cell carcinomas.
      However, tumor angiogenesis is not controlled simply by the presence of VEGF, and
      is likely regulated by several angiogenic factors produced by tumor and host
      cells. The goal of the present study was to determine the angiogenic profile of
      precancerous and cancerous lesions of the esophagus. Expression of mRNAs for
      VEGF, platelet derived endothelial cell growth factor (PD-ECGF), basic fibroblast
      growth factor (bFGF), and interleukin (IL)-8 was examined in six esophageal
      carcinoma cell lines and fresh biopsy specimens from 16 patients with invasive
      esophageal carcinoma by RT-PCR. Immunohistochemical analyses with antibodies
      against VEGF, PD-ECGF, bFGF, and IL-8 were performed on archival specimens of 60
      normal esophageal mucosa, 11 dysplasias and 49 carcinomas of the esophagus.
      Microvessels were stained with anti-CD34 antibody and quantified by counting the
      number of vessels in a x200 field in the most vascularized areas of the tumor.
      Esophageal carcinoma cell lines and tumor tissues expressed mRNAs for one or more
      these angiogenic factors at various levels. An initial increase in vessel density
      and enhanced expression of PD-ECGF and VEGF were observed in dysplastic
      epithelium. Vessel density was significantly higher in more advanced lesions.
      bFGF and IL-8 were not expressed in dysplasias and mucosal carcinomas, but
      expression was increased in late stage squamous cell carcinoma. These findings
      suggest that the angiogenic switch is a very early event in the development of
      invasive carcinoma. Several different angiogenic factors produced by tumor cells
      and host cells may regulate angiogenesis during different steps of esophageal
      carcinogenesis.

PMID- 14719062
TI  - Expression of protein kinase C isoenzymes in benign hyperplasia and carcinoma of
      prostate.
AB  - Protein kinase C family consists of 11 isoforms, classified into 3 categories
      according to their structure and mechanisms of activation. These isoenzymes are
      involved in processes, which maintain intracellular homeostasis. Alterations in
      activity, amount or distribution of protein kinase C (PKC) isoenzymes may cause
      cellular proliferation or induce apoptosis. We have studied and compared the
      expression levels of several PKC isoforms in benign prostatic hyperplasia (BPH)
      and prostate cancer (PCa). These are PKCs alpha (alpha), beta (beta), delta
      (delta), epsilon (epsilon), zeta (zeta), eta (eta), which have been detected as
      major isoforms in prostate tissue. Paraffin sections of 25 benign prostatic
      hyperplasia (BPH) and 25 of prostatic carcinoma (PCa) were examined for
      expression of PKC alpha, beta, delta, epsilon, zeta, and eta. Expression of PKC
      beta was examined in additional 3 BPH and 3 PCa using Western blot analysis. We
      found a significant high level of expression of PKC isoforms alpha, beta, epsilon
      and eta in PCa compared to BPH (p<0.01). Using backward logistic regression, we
      found changes in PKC epsilon expression to be most significant between malignant
      compared to benign tumor tissue specimens. Immunostaining for PKCs alpha, beta
      and eta in addition to PKC epsilon may aid in distinguishing between benign and
      malignant prostatic disease.

PMID- 14719063
TI  - Novel CD43 specific phage antibodies react with early stage colorectal tumours.
AB  - Two panning strategies have been used to isolate phage antibody clones that
      recognise an intracellular epitope of CD43. Firstly, a naive scFv library was
      panned against a 15-mer CD43 synthetic peptide (RGGKRNGVVDAWAGP), and secondly
      the naive library was panned against native CD43, isolated from whole cell lysate
      of Colo205 cells, followed by selection with the synthetic CD43 peptide. Four
      phage antibodies (HapE8, F2, G9 and G11) were isolated and used in a preliminary
      immunohistochemistry study of CD43 expression on frozen colorectal adenoma and
      carcinoma tissue. The three antibodies HapE8, F2 and G11 showed a similar
      reactivity pattern, staining all adenomas and Dukes' A carcinomas, but only 2/4
      Dukes' B and 1/9 Dukes' C. Antibody HapG9 similarly bound to 5/5 adenomas, but
      only 1/5 Dukes' A carcinoma and no tumours of a more advanced stage. No
      reactivity with normal colonic epithelium was observed but cross-reactivity with
      stromal lymphocytes was seen. These new anti-CD43 antibodies are likely to prove
      useful as screening tools in the detection of colorectal adenomas.

PMID- 14719065
TI  - Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its
      relationship to clinical features.
AB  - Aberrant promoter methylation of CpG islands of tumor suppressor genes inhibits
      expression of the genes and may lead to tumorigenesis. We investigated the
      aberrant methylation profile of potential tumor suppressor genes of p15, p16,
      SOCS-1, and Wnt signaling pathway in colorectal cancers and correlated the data
      with clinical findings. Cancerous and nearby non-cancerous tissues of 185
      sporadic colorectal cancer samples were studied. Methylation specific PCR was
      performed to explore the mechanism of inactivation in p15, p16, SOCS-1, E
      cadherin, APC, GSK-3beta, and Axin1 genes. Aberrant promoter methylation in p15,
      p16, SOCS-1, E-cadherin, APC, GSK-3beta, and Axin1 genes were 5.9, 7.0, 3.8, 5.9,
      12.4, 2.2, and 0% for cancerous tissues, respectively, whereas the frequencies
      were 3.8, 0, 0, 7.0, 2.7, 0.5, and 0% for nearby non-cancerous tissues,
      respectively. The frequency of aberrant promoter methylation of cancerous tissues
      was significant higher than non-cancerous tissues in p16, SOCS-1, and APC genes
      (p<0.05) and methylation status of these genes had no clear relationship with
      clinical parameters. Of the 66 patients who showed at least one aberrant promoter
      methylation in the tumor-suppressor genes, 5 (7.6%) patients demonstrated
      multiple methylation phenotype (methylation > or =3) and associated with
      increased lymph node metastasis (p=0.036). Our findings suggest that inactivation
      of some tumor suppressor genes through aberrant promoter methylation of CpG
      islands may play a role in the development of colorectal cancer and methylation
      inactivation of these genes except p16 and SOCS1 may occur at the precancerous
      stage. Multiple methylation pathways may be involved in the tumorigenesis of
      colorectal cancer and associated with aggressiveness of clinical disease.

PMID- 14719064
TI  - Overexpression of gastrin and c-met protein involved in human gastric carcinomas
      and intestinal metaplasia.
AB  - Many studies have investigated the expression of c-met and c-erbB2 protein in
      human gastric adenocarcinomas, but the expression of gastrin protein in human
      gastric cancer and the relationship between gastrin and c-met are unknown. We
      have constructed a tissue microarray containing 408 formalin-fixed and paraffin
      embedded human tissue blocks, including tissues containing intestinal metaplasia
      (IM, n=72) and primary tumors (n=232), as well as normal gastric mucosa (n=104)
      from patients with gastric cancer. Immunohistochemistry (IHC) was used for
      detecting gastrin, c-met and c-erbB2 proteins. Gastrin was detected in 13.5%
      (7/52) and c-met in 15.3% (11/72) of IM cases. In gastric carcinomas, 48.4%
      (103/213) of cases expressed gastrin, 68.8% (148/215) expressed c-met, and 5.5%
      (11/200) expressed c-erbB2. Gastrin and c-met protein expression were
      significantly higher in gastric tumor tissue than in IM (P<0.0001).
      Overexpression of c-erbB2 protein was detected in gastric carcinomas but not in
      normal gastric mucosa (P<0.05). Expression of gastrin and c-met protein was
      associated (P<0.01), but no significant difference was found on the changes of
      gastrin, c-met and c-erbB2 expression in gastric cancer with tumor stage, grade
      of differentiation or tumor type. These results indicate that gastrin and c-met
      play a role in the early process during malignant transformation of the gastric
      mucosa.

PMID- 14719066
TI  - Decreased FHIT protein expression correlates with a worse prognosis in patients
      with diffuse large B-cell lymphoma.
AB  - This study was conducted to evaluate the expression of the presumptive tumor
      suppressor gene, FHIT (fragile histidine triad) and its clinical significance in
      non-Hodgkin's lymphoma (NHL). Nine lymphoma cell lines, 62 NHL samples including
      31 diffuse large B-cell lymphomas (DLBCLs), and 10 benign hyperplastic lymph
      nodes were analyzed for FHIT transcription using RT-PCR, with DNA sequencing
      performed where aberrant transcripts were found. Immunohistochemistry (IHC)
      studies were conducted for evaluation of FHIT protein expression with clinical
      data collected for assessment of the clinical relevance of the FHIT expression in
      DLBCLs. Eight of nine (88.9%) cell lines showed abnormal FHIT mRNA transcription,
      including 4 with co-existence of normal and aberrant transcripts, and 4 with
      absence of mRNA expression. Abnormal FHIT mRNA expression was noted in 10 (32.3%)
      DLBCL patients, including 3 with loss of FHIT mRNA expression and 7 with aberrant
      transcripts. In all NHLs, abnormal FHIT transcripts were determined for 17 of 62
      patients (27.4%). Regarding the FHIT protein expression in DLBCLs, 41.9% showed
      strong FHIT IHC expression (2+), where 58.1% patients revealed reduced (1+) or
      absence (0) of FHIT protein. Decreased FHIT protein expression was associated
      with a worse survival after univariate and multivariate analysis. Our result
      indicates that abnormal FHIT mRNA expression is noted frequently in NHL cell
      lines and a certain proportion of NHL patients, and decreased FHIT protein
      expression indicates a significantly worse prognosis in DLBCLs.

PMID- 14719067
TI  - Role of complex cadherins in cell-cell adhesion evaluated by spheroid formation
      in renal cell carcinoma cell lines.
AB  - We have previously shown that renal cell carcinoma (RCC) cell lines expressed a
      complex set of cadherins, e.g. E-cadherin, N-cadherin and cadherin-6. It is also
      reported that E-cadherin and cadherin-6 have a predictive value for estimating a
      patient's prognosis in RCC. However, E-cadherin is infrequently expressed in RCC
      as compared with N-cadherin and cadherin-6. In the present study, therefore, we
      performed a functional analysis of these cadherins as a cell adhesion molecule
      using spheroid culturing and spheroid-blocking assay. In E-cadherin expressers,
      compact spheroid formation was observed, and it was inhibited by anti-E-cadherin
      antibody. In contrast, in E-cadherin-absent lines, cadherin-6 apparently played a
      role to form relatively loose spheroids and this spheroid formation was inhibited
      by anti-cadherin-6 antibody. In both spheroids, the anti-N-cadherin antibody
      could not inhibit their formation, suggesting that N-cadherin was not an
      essential molecule for spheroid formation in the cell lines expressing complex
      cadherins. The anti-N-cadherin antibody inhibited spheroid formation only in the
      cell line that expressed N-cadherin alone. Using western blot analysis,
      immunohistochemistry and immunoprecipitation, these cadherins were linked to
      catenins to make a functional adhesion molecule. In conclusion, E-cadherin and
      cadherin-6 are shown to act in cell-cell adhesion whereas N-cadherin might play a
      somewhat different role from cell-cell adhesion in RCC cell lines.

PMID- 14719068
TI  - Mutation analysis of the BRAF codon 599 in malignant pleural mesothelioma by
      enriched PCR-RFLP.
AB  - BRAF encodes a RAS-regulated serine/threonine kinase that mediates the pathway
      for cell growth and malignant transformation. Point mutations of BRAF were
      reported recently in 66% of melanomas, over 30% of thyroid papillary and low
      grade ovarian cancers, and a smaller percentage of other human cancers. Mutations
      in malignant cells were reported to occur only in exons 11 and 15. Among these
      mutations, BRAF V599E is most frequent and proved to invert its transcript to the
      dominant active form. To exclude the interference of co-existing normal cells in
      clinical samples, we developed a new enriched PCR-RFLP assay for detecting
      mutations of BRAF codon 599 mutation. The sensitivity of this assay was examined
      to find that one mutant allele among 10(2) wild-type alleles could be detected.
      We applied this method for 53 cases of primary malignant pleural mesotheliomas
      (MPMs) and 6 cell lines and found no mutations in these samples. Our results
      demonstrate that the developed enriched PCR-RFLP is a sensitive assay to detect
      BRAF codon 599 mutation. However, it may be a rare type of mutation in MPMs. Our
      new assay is useful and can be applied for screening of BRAF codon 599 mutation
      in various kinds of clinical samples.

PMID- 14719069
TI  - Primary toremifene treatment for elderly postmenopausal women with breast cancer.
AB  - Among patients with breast cancer who consulted the Department of Radiology,
      Kochi Medical School to undergo breast-conservation treatment, toremifene (TOR)
      alone was administered to 7 postmenopausal women as initial treatment for reasons
      such as the patient's desire, advanced age, and concomitant disease. In 6
      patients, breast-conserving surgery was performed 1-12 months after the start of
      the administration of TOR alone. A 90-year-old patient has been treated with TOR
      alone for 56 months, and is being followed up. Six of 7 patients showed 50% or
      greater reduction of tumors, including 1 in whom the administration of TOR alone
      for 5 months reduced the tumor from a clinical diagnosis of skin invasion (T4b)
      to T1c, allowing lumpectomy under local anesthesia. In one patient, there were no
      changes (reduction ratio: 14%). No progressive disease was detected in any
      patient. In this study, the administration of TOR alone markedly reduced tumors
      in patients with estrogen receptor (ER)-positive breast cancer, facilitating down
      staging. Treatment with TOR alone may be a useful neoadjuvant therapy or single
      therapy in elderly patients.

PMID- 14719070
TI  - Ribozyme mediated down-regulation of thrombospondin receptor CD36 inhibits the
      growth of the human osteosarcoma cell line.
AB  - Thrombospondin-1 (TSP1) is known to possess tumor suppressor functions. In
      contradiction, TSP1 enhances the stromal vascularization and growth of certain
      cancers. A cell adhesion receptor, CD36, has been shown to interact with a ligand
      TSP1. We studied how CD36 affects the growth of the osteosarcoma cell line (HOS)
      expressing TSP1. We used the anti-CD36 ribozyme to specifically suppress CD36
      gene expression in the HOS. The expression of the CD36 mRNA was significantly
      suppressed in the ribozyme-introduced cell line (HOS/Rz). The transformant HOS/Rz
      markedly decreased its growth. The growth of the osteosarcoma cell line HOS may
      be regulated by autocrine or paracrine loop TSP1 and CD36.

PMID- 14719071
TI  - Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and
      these signal pathways are amplified in cisplatin-resistant squamous cell
      carcinoma.
AB  - cis-Diaminodichloroplatinum (II) (cisplatin) is one of the most effective
      anticancer drugs and is widely used for the treatment of squamous cell carcinoma
      (SCC). However, its efficacy is often limited due to the development of
      resistance. Although several factors implicated in cisplatin resistance have been
      identified, the resistance mechanisms in detail are not fully understood yet. In
      the present study, we have examined the implication of survival signaling
      pathways in cisplatin-resistance. Cisplatin induced activation of Ras and its
      downstream effector kinases, Raf/MEK/ERK in UM-SCC-23 human squamous cell
      carcinoma, suggesting that this anticancer drug activates survival signal pathway
      in addition to apoptosis signals. In cisplatin-resistant UM-SCC-23 in culture,
      which we have established, the protein levels of Ras, Raf-1 and MEK were
      drastically elevated compared to parent UM-SCC-23, and ERK and Akt signals were
      constitutively activated. U0126, an inhibitor for MEK and LY294002, an inhibitor
      for phosphatidylinositol 3-kinase (PI3K), sensitized resistant UM-SCC-23 to
      cisplatin-induced cell death. These results indicate that Raf/MEK/ERK and
      PI3K/Akt signal cascades may play a considerable role in cisplatin resistance in
      SCC.

PMID- 14719072
TI  - Thymidine kinase and thymidine phosphorylase level as the main predictive
      parameter for sensitivity to TAS-102 in a mouse model.
AB  - TAS-102 is a new oral anti-cancer drug preparation, composed of a 1:0.5 mixture
      (on a molar basis) of alpha,alpha,alpha-trifluorothymidine (FTD) and 5-chloro-6
      [1-(2-iminopyrrolidinyl)methyl]-2,4(1H,3H)-pyrimidinedione hydrochloride (TPI).
      TAS-102 currently undergoing clinical trials, has been demonstrated to have at
      least two mechanisms, inhibition of TS and incorporation into DNA. We
      hypothesized that the thymidine metabolism enzyme may be a crucial factor that
      affects the antitumor activity of TAS-102. In the present study, we measured the
      enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and
      thymidilate synthase (TS) in human cancer xenografts to investigate the
      contribution of these enzymes to the sensitivity of TAS-102. Antitumor activity
      of TAS-102 appears to be associated with TK, tumor growth and TS. However, the
      most related factors in this study were the TK and TP ratio. There was a
      significant correlation (p=0.04) between tumor growth inhibition and this ratio.
      These results suggested that the activation and degradation pattern of FTD plays
      an important role in the efficacy of TAS-102 and that it is possible to use the
      TK/TP ratio to predict response to TAS-102 therapy. We also studied the influence
      of TPI on the capacity of exogenous dThd to reverse FTD-dependent growth
      inhibition. Thymidine (dThd) levels rescued the effect of FTD in vitro and
      significantly increased in serum after administration of TAS-102 or TPI alone but
      not FTD alone. This may suggest the possibility of a decrease in antitumor
      effect. However, our study indicated that the therapeutic index was clearly
      increased by FTD combined with TPI, compared with FTD alone, suggesting FTD
      induced toxicity to sensitive host tissue can be selectively reversed with dThd.
      In conclusion, TK and TPI effects on TP play important roles in the cytotoxic
      action of TAS-102, and it is possible to use the TK/TP ratio to predict more
      precisely individual resistance or sensitivity.

PMID- 14719073
TI  - The use of Doppler ultrasound in evaluation of breast cancer metastasis to
      axillary lymph nodes.
AB  - The formation of microvessels in tumors by angiogenesis is considered to be an
      important prognostic factor, and closely correlates with lymph node metastasis.
      We used color Doppler ultrasound to examine the relationship between the amount
      of blood vessels in tumors and pulsatility index (PI), and tumor size in breast
      cancers, with and without regional lymph node metastasis. Doppler ultrasound was
      performed on 80 patients with breast cancer prior to surgery. The concentration
      of vascular endothelial growth factor (VEGF) within the tumors was measured
      following surgery in 42 cases chosen at random. In the negative metastatic nodes
      group, the number of vessels in the tumor correlated positively with tumor
      diameter. In the positive metastatic nodes group, however, the number of blood
      vessels in the tumor did not correlate with tumor diameter. Differences in tumor
      vascularity between node positive and negative groups were useful in determining
      the status of node metastasis in subsequent analysis. Fifteen of 17 cases of
      tumors that measured <20 mm, and in which there were no blood vessels, were node
      negative. There were no node-negative tumors measuring >20 mm in diameter
      (p=0.003). Conversely, in nodes with positive metastasis, blood vessels were
      observed in 5 of 7 tumors that measured <15 mm in diameter (p=0.019). These
      findings may be useful in estimating the likelihood of metastasis to regional
      lymph nodes. PI was directly proportional to tumor size in the negative nodes
      group (r=0.47). There was no such correlation in the positive nodes group. There
      was no correlation between VEGF concentration in the tumor and the number of
      blood vessels in that tumor. In conclusion color Doppler analysis of blood
      vessels appears to be useful in predicting lymph node metastasis, especially for
      small tumors.

PMID- 14719075
TI  - Apoptosis: escaping strategies in human skin cancer (Review).
AB  - Apoptosis must be considered a rescue mechanism that controls the integrity of
      the cell erasing aberrant clones and it is likely that failure of apoptosis
      constitutes a key factor responsible for tumour formation, progression and
      resistance to drugs. Several genes (e.g. survivin, bcl-2 family, p53) are
      involved in these pathways. Much work still needs to be done to identify the
      molecular pathway of apoptosis resistance but restoration of the apoptotic
      response represents a crucial new therapeutic target for cancer treatment.

PMID- 14719074
TI  - Regulation of telomerase and its hTERT messenger in colorectal cancer.
AB  - Telomeres are the distal ends of human chromosomes composed of tandem repeats of
      the sequence TTAGGG. In most human somatic cells, telomerase activity is
      undetectable, and the telomere length is progressively shortened during cell
      proliferation, leading to cellular senescence. In contrast, telomerase is
      activated in the vast majority of cancer cells, including colorectal cancer. The
      human telomerase complex is comprised of multiple components, but telomerase
      reverse transcriptase (hTERT) is the most important component for the control of
      telomerase activity. The p53 protein is a transcription factor with multiple
      biological activities, including cell cycle arrest and/or apoptosis upon DNA
      damage, hypoxia and oncogene activation; this requires transactivation or
      repression of specific target genes by wild-type p53. To better understand if a
      link between hTERT/telomerase regulation and p53 status exists in colorectal
      carcinogenesis, we analysed 43 cases of colorectal carcinoma for hTERT mRNA
      expression and telomerase activity. Moreover, a complete analysis of p53 status
      was performed. Alterations of p53 gene were found in 44.19% of cases and missense
      point mutations represented a high proportion of p53. Both telomerase activity
      (p=0.014) and hTERT expression (p=0.03) were significantly associated with p53
      mutations, suggesting a role of p53 in the signaling pathway for telomerase
      control.

PMID- 14719076
TI  - In vitro study of farnesyltransferase inhibitor SCH 66336, in combination with
      chemotherapy and radiation, in non-small cell lung cancer cell lines.
AB  - K-ras alterations have been reported in 20-30% of non-small cell lung cancer
      (NSCLC) and represent a suitable target for the development of novel anticancer
      agents, such as Farnesyl transferase inhibitors (FTi), a new class of agents
      inhibiting the post-translational modification of the K-ras proteins. The
      effectiveness of FTi SCH66336 in inhibiting cell proliferation and deranging cell
      cycle of NSCLC cell lines as well as its interaction with chemotherapy or
      radiation have been evaluated. The activity of FTi SCH66336, alone or in
      combination with paclitaxel, gemcitabine, and radiotherapy, was examined in 3
      cell lines, A-549, LX-1 and CaLu-6, by colorimetric MTT assay. Cell cycle
      perturbation and apoptosis were also assessed by cytofluorimetric analysis. The
      activity of SCH 66336 was found to be concentration- and time-dependent. The
      effect of SCH 66336, as demonstrated by cell growth recovery experiments,
      resulted cytostatic and it was superimposable in both cell lines bearing 2
      different K-ras mutations (A-549 and LX-1) and in K-ras wild-type Ca-Lu-6. In all
      cell lines the combination of SCH 66336 and paclitaxel resulted in a synergism of
      action when SCH 66336 followed paclitaxel treatment, whereas, antagonism was
      found when SCH 66336 preceded paclitaxel treatment. No significant synergism or
      addition with SCH 66336 followed by radiation treatment was noted. Different cell
      cycle phase blocks at various drug concentrations were observed. In conclusion,
      SCH 66336 displays concentration-dependent cytostatic antitumour activity and
      schedule-dependent synergy with 2 commonly used anticancer agents in NSCLC cell
      lines. Further clinical testing of these combinations is warranted.

PMID- 14719077
TI  - Regulation of squamous cell carcinoma antigen production by E-cadherin mediated
      cell-cell adhesion in squamous cell carcinoma cell line.
AB  - Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and
      management of squamous cell carcinoma. It is well known that cell-cell adhesion
      is important for progression of cancer. However, it is not clarified whether cell
      cell adhesion affects SCCA production in squamous cell carcinoma. The present
      study was, therefore, undertaken to investigate whether E-cadherin-mediated cell
      cell adhesion affects SCCA production in squamous cell carcinoma of the uterine
      cervix. SKG-IIIa cells or CaSki cells, cervical squamous cell carcinoma cell
      lines, were treated with anti-E-cadherin antibodies (1 microg/ml) up to 72 h. The
      cells were dissociated, and SCCA content in the cytosol and SCCA mRNA levels were
      significantly decreased compared to the control group treated with mouse IgG.
      Secondly, the signaling pathway for SCCA production mediated by E-cadherin was
      examined. Phosphatidylinositol (PI) 3-kinase is a well-known mediator of E
      cadherin-mediated biological events. The treatment with a PI 3-kinase inhibitor
      suppressed SCCA production in SKG-IIIa cells. It is concluded that E-cadherin
      mediated cell-cell adhesion maintains SCCA production through PI 3-kinase in
      squamous cell carcinoma.

PMID- 14719078
TI  - Protein levels of p21, p27, cyclin E and Bax predict sensitivity to cisplatin and
      paclitaxel in head and neck squamous cell carcinomas.
AB  - Regression of tumor mass by chemotherapy is caused by growth suppression and/or
      apoptosis of tumor cells. Therefore, expression levels of cell cycle molecules
      and apoptosis should be predictive markers for the efficacy of a drug. In the
      present study, the relationship between expression of molecules in the cell cycle
      and apoptosis and chemosensitivity was investigated in head and neck squamous
      cell carcinoma cell lines. Expression of p53, p21, p27, cyclin D1, cyclin E, and
      Bax in 17 such cell lines were analyzed by Western blot analysis. The
      concentrations of four chemotherapeutic agents (cisplatin, 5-FU, vincristine, and
      paclitaxel) resulting in 50% cell growth inhibition were calculated as IC50
      values for each cell line. Cell cycle analysis was performed using a FACScan flow
      cytometer. Cells with strong expression of p21, p27, or Bax showed significantly
      higher sensitivity to cisplatin, and cells with strong expression of Bax or weak
      expression of cyclin E showed significantly higher sensitivity to paclitaxel.
      Cisplatin most effectively killed cells expressing both p21 and p27 or either at
      G1 phase. Though the assessments of p21, p27, Bax, and cyclin E expression in
      tumor tissues have been reported to be useful as prognostic factors in head and
      neck squamous cell carcinoma, these correlations might not only describe the
      malignant biological behavior of the tumor, but also the response to
      chemotherapy. Furthermore, p21/p27 expression might be a useful guide for the
      choice of chemotherapeutic agents.

PMID- 14719079
TI  - Expression of uteroglobin and matrix metalloproteinase-9 genes in endometrial
      cancer: relationship to estrogen and progesterone receptor status.
AB  - Uteroglobin (UG) is a protein expressed in secretory epithelia of different
      tissues, including the human endometrium, where the expression levels are
      modulated by ovarian steroids. There is evidence that UG, which is a potent
      inhibitor of the activity of phospholipases A2, has anti-proliferative effects
      and we have previously demonstrated that enforced UG expression reverts the
      transformed phenotype in the endometrial cancer cell line HEC-1A. The objective
      of the present study was to evaluate the expression of UG in endometrial cancer
      tissues. Furthermore, the estrogen (ER) and progesterone (PR) receptor status was
      investigated. Finally, the amount of expression of matrix metalloproteinase-9
      (MMP-9), which is stimulated by estrogens, was determined. Twenty-five patients
      were included in the study. Total RNA was extracted from tissue samples obtained
      at surgery. UG, ERalpha, ERbeta, PR transcripts were analyzed by RT-PCR both in
      tissues and in different endometrial cancer cell lines. The levels of MMP-9 and
      of the tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) mRNA were
      determined by real-time RT-PCR. The statistical analysis of the results was based
      on Chi-square and t-test. UG expression was found in 73% of cases. No difference
      in the histopathological features between tumors expressing or not expressing UG
      was observed. The presence of UG significantly correlated with the expression of
      ERalpha and PR. The amount of MMP-9 was higher in UG+ and ERalpha+ tumors.
      Similar correlations were found in cell lines. Thus, our results indicate that
      the presence of UG in the majority of cases of endometrial carcinoma that were
      investigated, hypothetically a favorable disease marker, appears to be
      counteracted by high levels of MMP-9 expression.

PMID- 14719080
TI  - Vascular endothelial growth factor assessment in different blood fractions of
      gastrointestinal cancer patients and healthy controls.
AB  - Vascular endothelial growth factor (VEGF) is known to play a central role in
      tumour angiogenesis. Up to now inconclusive data have been published on the
      clinical-biological significance of circulating VEGF and on the most suitable
      blood fraction for measuring it. The aims of this pilot study were to assess VEGF
      in blood compartments of 16 healthy control volunteers and 56 gastrointestinal
      cancer patients, prospectively collected, to identify the most suitable blood
      fraction for the determination of VEGF and to evaluate its possible clinical
      biological significance. Samples of serum (S) and plasma (P) in both sodium
      citrate (SC) and sodium citrate-theophylline-adenosine-dipyridamole (CTAD) were
      collected from venous blood. After the centrifugation and separation methods VEGF
      levels were detected by ELISA in: S, plasma-platelets poor (P-PP), plasma
      activated platelets rich (P-APR) and blood-lysed whole (B-LW). The best
      differentiation between healthy control volunteers and cancer patients in VEGF
      level was seen for P-APRCTAD (mean value: 278 pg/ml vs 77 pg/ml; p=0.0036 by t
      test). No significant correlation among the blood fractions of VEGF analysed and
      clinical-pathological features was found. Our data suggest that P-APRCTAD blood
      fraction, obtained according to well standardised conditions, could represent the
      most suitable compartment for the assessment of VEGF. We suggest that VEGF levels
      in P-APRCTAD could play a role as an angiogenic marker of malignant
      gastrointestinal transformation. Further studies on a larger series of patients
      and healthy controls with the same experimental methodological conditions are
      required to confirm our preliminary conclusions.

PMID- 14719081
TI  - Resveratrol inhibits cell proliferation and induces apoptosis of human breast
      carcinoma MCF-7 cells.
AB  - Resveratrol, which is found in grapes and wine, has been reported to have a
      variety of important pharmacological effects including anti-inflammatory, anti
      platelet, and anti-carcinogenetic properties. In this study, using the human
      breast cancer cell line MCF-7, we have analyzed a possible mechanism by which
      resveratrol could interfere with cell cycle control and induce cell death.
      Resveratrol treatment of MCF-7 cells resulted in a dose-dependent inhibition of
      the cell growth and the cells accumulated at the S phase transition of the cell
      cycle at low concentrations, but high concentrations do not induce S phase
      accumulation. The anti-proliferative effects of resveratrol were associated with
      a marked inhibition of cyclin D and cyclin-dependent kinase (Cdk) 4 proteins, and
      induction of p53 and Cdk inhibitor p21WAF1/CIP. Growth suppression by resveratrol
      was also due to apoptosis, as seen by the appearance of a sub-G1 fraction and
      chromatin condensation. In addition, the apoptotic process involves activation of
      caspase-9, a decrease of Bcl-2 as well as Bcl-XL levels, and an increase of Bax
      levels.

PMID- 14719082
TI  - Petasiphenol which inhibits DNA polymerase lambda activity is an inhibitor of in
      vitro angiogenesis.
AB  - Petasiphenol, a polyphenolic compound from a Japanese vegetable (Petasites
      japonicus) which is a DNA polymerase lambda selective inhibitor, was demonstrated
      as a potent antiangiogenic agent in this study. Petasiphenol showed suppressive
      effects on in vitro angiogenesis assays, human umbilical vein endothelial cell
      (HUVEC) proliferation, tube formation on reconstituted basement membrane and
      chemotaxis in a dose-dependent manner (10-100 microM). However, treatment of
      HUVEC with petasiphenol did not affect 72 kDa matrix metalloprotease activity at
      these concentrations. Petasiphenol at higher 50 microM also suppressed
      microvessel outgrowth in ex vivo angiogenesis assay using a rat aortic ring.
      Taken together, petasiphenol could act as a potent antiangiogenic compound for
      preventing tumor and be useful to design therapeutic agents.

PMID- 14719083
TI  - Prostate derived Ets transcription factor shows better tumor-association than
      other cancer-associated molecules.
AB  - We previously reported that prostate derived Ets transcription factor (PDEF) is a
      breast tumor-associated molecule. To obtain further insights into PDEF expression
      in other human tumor types, a cDNA library database from human adult normal and
      tumor tissues was compiled and searched for PDEF distribution. The results showed
      that PDEF is present at relative higher frequencies in the cDNA libraries from
      brain, breast, lung and ovarian tumors in comparison to those from the
      corresponding normal tissues. RT/PCR analysis of PDEF expression in ovarian
      tumors confirmed that PDEF is expressed in 36 out of 51 (71%) ovarian tumors.
      Further comparison of the distribution of PDEF with other widely recognized
      cancer-associated molecules showed that PDEF has more restricted distributions
      than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human
      tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin
      and telomerase in cDNA libraries from brain (except survivin), breast, lung and
      ovarian tumors. These data together show a better tumor-association for PDEF and
      suggest that PDEF is a more suitable target for developing specific cancer
      therapies.

PMID- 14719084
TI  - Trends in long-term survival following surgery for gastric cancer: a single
      institution experience.
AB  - We reviewed cases at our institution in an attempt to identify temporal trends in
      survival of patients with operable gastric cancer. We analyzed data on 1632
      patients who received a diagnosis of gastric adenocarcinoma between 1975 and 1995
      and who underwent surgery at our institution. The time trends were examined by
      comparing three time periods (1975-1984, 1985-1989 and 1990-1995). Over time
      there was an improvement in the R0 resection rate: the rate significantly
      increased from 65% to 83%. Short-term outcomes following surgery have improved,
      with 30-day mortality dropping from 3.5% to 1%. The overall survival curve
      continuously improved with time. The five-year survival rates improved from 43%
      to 61%. The increased use of extended lymph node dissection with careful
      examination for metastases allowed for more accurate TNM staging. The incidence
      of peritoneal failure remains high, with peritoneal recurrence observed in 49% of
      the patients who underwent R0 resection between 1985 and 1995 and who experienced
      recurrences. Our results demonstrated that current efforts to improve gastric
      cancer management are finally meeting with noticeable success. However, advanced
      stage cancer remains a medical problem. Multimodal treatment of advanced disease
      will be an important theme in coming years.

PMID- 14719085
TI  - Efficacy of 9-cis-retinoic acid and N-(4-hydroxyphenyl) retinamide alone and in
      combination in mammary cancer prevention.
AB  - As demonstrated in several in vitro and in vivo cancer models, retinoids have
      chemopreventive activity. The present studies were performed to evaluate the
      efficacy of 9-cis-retinoic acid (9-cis-RA) and N-(4-hydroxyphenyl) retinamide (4
      HPR), alone and combined, in preventing mammary cancers. Female Sprague-Dawley
      rats received N-methyl-N-nitrosourea (MNU), 50 mg/kg BW, either at 50 days of age
      (experiment I, young rats) or at 100 days of age (experiment II, older rats). In
      experiment I, 9-cis-RA (60 mg/kg of diet), 4-HPR (586 mg/kg of diet), or the
      combination were evaluated; in experiment II, 9-cis-RA (30 mg/kg of diet), 4-HPR
      (196 mg/kg of diet), or the combination were tested. There were no signs of
      toxicity in either study. In the young rats, there were only slight reductions
      (15-20%) in the number of mammary cancers when the agents were given alone. In
      the older rats, lower doses of 9-cis-RA or 4-HPR alone were highly effective;
      with 61% and 46% reductions in the number of mammary cancers, respectively. The
      combination of retinoids in the young rats caused a 49% reduction in mammary
      cancers, while in the older rats the combination resulted in a 96% reduction.
      Thus, lower doses of the retinoids caused more striking inhibition of mammary
      cancers in older rats than the higher doses given to younger animals. In both
      experiments, the two retinoids in combination produced an additive effect,
      suggesting that they may inhibit mammary cancers by different mechanisms.

PMID- 14719086
TI  - In vitro comparison of Essiac and Flor-Essence on human tumor cell lines.
AB  - Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North
      American cancer patients during chemo- and radiation therapy. In vitro studies on
      the antiproliferative and differentiation inducing activities of these teas were
      performed. ES and FE showed negligible antiproliferative activity on Jurkat
      leukemia cells. Both herbal teas inhibited 50% (IC50) of MCF7 breast cancer cell
      growth at 1/10 dilution. The IC50 was about 1/40 and 1/10 dilution of FE and ES
      respectively for MDA-MB-468 human breast cancer cells. The IC50 for HL60 cells
      was at 1/10 dilution of FE and less than 1/10 dilution of ES. ES at 1/10 dilution
      induced expression of non-specific esterase in 16% of HL60 cells, compared to
      about 5% in FE treated cells and untreated controls. ES treatment of HL60 cells
      induced 47-67% nitroblue tetrazolium positive staining cells compared to 24.6+/
      3.1% in cells treated with 1/10 dilution of FE. Flow cytometry analysis showed
      that both ES and FE treatment between 1/10 and 1/100 dilutions only slightly
      affected the cell cycle progression of MCF7, MDA-MB-468, Jurkat and HL60 cells.
      Our data show that both ES and FE herbal teas demonstrated antiproliferative and
      differentiation inducing properties in vitro only at high concentrations. Further
      research is needed to elucidate the in vivo activities.

PMID- 14719087
TI  - Effect of single dose irradiation on human glioblastoma spheroids in vitro.
AB  - Investigation of the predictive value of a radiosurgery-relevant treatment of
      glioblastoma spheroids. Organotypic multicellular spheroids were cultured and
      irradiated (20 Gy). Morphology, apoptosis and immunohistochemical expression of
      p53, p21, MIB-1, TGF-beta and VEGF were examined 4 h, 24 h, 7 days, and 14 days
      following treatment. Cell proliferation decreased, while apoptosis was increased.
      No morphological damage was observed. p53 expression was significantly increased
      after 4 h. TGF-beta and VEGF expression were only slightly altered. Particularly
      early changes in proliferation and apoptosis can be observed in spheroids.
      Individual response differences suggest spheroids of human gliomas to be useful
      for monitoring radiosurgery effects.

PMID- 14719088
TI  - Human soluble p66 and p51 tumor-associated antigens promote the suppression of
      rat mammary tumors in comparison to commercial human albumin.
AB  - This study examined whether the soluble 66- and 51 kDa tumor-associated antigens
      (sTAA), isolated from the serum of breast cancer patients, possess specific
      suppressive effects on chemically-induced rat mammary tumorigenesis in comparison
      to commercial human albumin. Dimethylbenzanthracene (DMBA, 10 mg/rat, 2
      administrations) was used to induce mammary tumors in 8-week-old Sprague Dawley
      rats. After the appearance of many large tumors, preparations of sTAA (50-60
      micro g/rat in 0.5 ml sterile PBS) or commercial human albumin (HA, in the same
      doses as sTAA) were administered weekly, for 10-14 more weeks. The following
      groups of mammary tumor-bearing rats were studied: i) control non-treated rats,
      ii) rats treated with HA, iii) rats treated with sTAA. The experiment was
      terminated when tumors in 70% of the rats became ulcerous. The treatment with
      sTAA significantly decreased, compared to controls, the yield and total area of
      the tumors. In rats treated with sTAA, the appearance of new tumors stopped at
      week 5 as compared to week 7 in rats treated with HA and week 10 in control rats.
      In rats treated with sTAA, the time of appearance of ulcerous tumors increased to
      8 weeks, as compared to 6 weeks in controls and in rats treated with HA. Duration
      of the experiment increased from 11 weeks in controls to 12 weeks in rats treated
      with HA and to 14 weeks in rats treated with sTAA. We conclude that sTAA have
      tumor-suppressive properties, which are well-defined if the treatment is begun on
      small tumors.

PMID- 14719089
TI  - Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents
      doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and
      MDA-MB468 cells.
AB  - Significant emphasis is being placed on combination chemotherapy of cancer using
      cytotoxic agents and naturally occurring chemopreventive agents, having different
      mechanisms of action with non-overlapping toxicity. In this regard, here we
      assessed whether a cancer preventive agent silibinin synergizes the therapeutic
      potential of doxorubicin (Dox), cisplatin or carboplatin, the chemotherapeutic
      drugs, in both estrogen-dependent and -independent human breast carcinoma, MCF-7
      and MDA-MB468 cells, respectively. When tested alone, each of the four agents
      showed growth inhibition in both the cell lines in a dose- and a time-dependent
      manner. Based on their growth inhibitory effects, several combinations of
      silibinin (25-100 microM) with Dox (10-75 nM), cisplatin (0.2-2 microg/ml) or
      carboplatin (2-20 microg/ml) were next assessed for their synergistic, additive
      and/or antagonistic efficacy towards cell growth inhibition and apoptotic death.
      The strongest synergistic effects for cell growth inhibition [combination index
      (CI) 0.35 for MCF-7 and 0.45 for MDA-MB468 cells] were evident at a silibinin
      dose of 100 microM plus 25 nM Dox, in both the cell lines. Most of the CIs for
      other combinations of these three drugs with silibinin also suggested strong
      synergistic effects for cell growth inhibition in both MCF-7 and MDA-MB468 cells.
      In quantitative apoptosis studies, combination of silibinin with Dox resulted in
      much stronger apoptotic death compared to each agent alone in both cell lines. In
      case of silibinin combination with cisplatin, it showed no additional apoptotic
      effect in either cell line. Similarly, silibinin plus carboplatin combination
      showed stronger apoptotic effect only in MCF-7 cells. Together, these results
      suggest a possible synergism between silibinin and conventional cytotoxic agents
      for breast cancer treatment, and warrant further in vivo studies in pre-clinical
      breast cancer models.

PMID- 14719090
TI  - Development of a rapid genotyping method for single nucleotide polymorphisms and
      its application in cancer studies.
AB  - Single nucleotide polymorphisms (SNPs) in cancer-related genes can act as low
      risk genetic factors for the development of this disease. SNPs have also been
      shown to influence the efficacy and toxicity of various cytotoxic agents used in
      the treatment of cancer. Progress in these important areas of cancer research
      relies upon rapid, inexpensive and accurate means of SNP genotyping. In the
      present study we describe a fluorescent PCR-based method that utilizes single
      strand conformation polymorphism (SSCP) analysis to distinguish between different
      alleles. A real-time DNA fragment analysis platform and ultra-thin, re-useable
      gels allow short run times and hence a relatively high throughput to be achieved.
      A standardised procedure for the identification of optimal running conditions for
      each SNP is presented. We used this fluorescent-SSCP method to genotype SNPs in
      the MTHFR, p21, cyclin D1, MMP-2, vitamin D receptor, TNF-alpha and IL-6 genes.
      Multiplex PCR of two SNPs allows up to 500 genotypes per day to be evaluated with
      100% accuracy. The low start-up and running costs make this method particularly
      well suited for SNP genotyping studies that involve up to 1,000 DNA samples.

PMID- 14719091
TI  - Matrix metalloproteinase activation is an early event in doxorubicin-induced
      cardiotoxicity.
AB  - Matrix metalloproteinase (MMP) activation contributes to the development of
      various pathophysiological conditions, including dilated cardiomyopathy,
      congestive heart failure, and reperfusion injury. Increased oxidative and
      nitrosative stress have been implicated in the activation of MMPs and also in the
      cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Thus, we
      hypothesized that MMP activation occurs in DOX-induced cardiotoxicity. Male
      Balb/c mice received a single injection of DOX (25 mg/kg i.p.) and were
      sacrificed 12 h, 1, 2, 3 and 4 days later. Hearts and aortae were harvested for
      MMP zymography. DOX induced time-dependent activation of MMPs both in the heart
      and in the aortic tissue with an earlier onset in the latter. These results
      demonstrate that MMP activation is an early event in DOX-induced cardiotoxicity
      and raises the possibility that MMP inhibitors may influence the outcome of this
      severe complication.

PMID- 14719092
TI  - Arsenic trioxide-induced apoptosis is independent of CD95 in lymphatic cell
      lines.
AB  - The potency of arsenic trioxide (As2O3) as chemotherapeutic agent is under
      investigation in various clinical trials. As2O3 was shown to be a potent inductor
      of apoptosis, and several publications describe the involvement of caspases,
      reduction of mitochondrial membrane potential and modulation of intracellular
      glutathione level. However, little is known about the involvement of membrane
      bound cell death receptors. We investigated the role of CD95 and CD95L in As2O3
      mediated apoptosis in various lympho-haematopoietic cell lines. Basal CD95
      expression did not correlate with sensitivity to As2O3 and incubation with As2O3
      did not alter CD95-expression. We therefore chose two CD95 positive cell lines
      (CCRF-CEM and Jurkat) to analyse a potential activation of this pathway. We were
      able to induce apoptosis in these CD95 positive cell lines with activating anti
      CD95 antibodies and could block induction of apoptosis by inhibitory anti-CD95
      antibodies. In contrast we were not able to block As2O3-induced apoptosis by
      inhibitory anti-CD95 antibodies. We could block additive effects of arsenic
      trioxide and an apoptosis-inducing anti-CD95 antibody against CD95 to levels of
      arsenic trioxide alone using an inhibitory anti-CD95 antibody. Thus, our data
      provide no evidence for a role of the CD95L/CD95 pathway in As2O3-induced
      apoptosis.

PMID- 14719093
TI  - The role of protein kinase C-alpha in malignancies of the nervous system and
      implications for the clinical development of the specific PKC-alpha inhibitor
      aprinocarsen (Review).
AB  - Antisense oligonucleotide (ASO) technology offers a novel approach for the
      development of anti-cancer drugs. For example, the ASO aprinocarsen has been
      developed to specifically inhibit the intracellular signal transduction protein,
      protein kinase C-alpha (PKC-alpha). The clinical development of such specific or
      "new targeted" agents in cancer requires a comprehensive understanding of the
      target protein. This understanding is expected to improve the identification of
      patients who most likely will benefit from treatment with a specific inhibitor,
      such as aprinocarsen. In order to better understand the role of PKC-alpha in
      nervous system malignancies we here review the published literature on PKC-alpha
      expression in nervous system tumors, including glioblastoma multiforme. In pre
      clinical experiments aprinocarsen had demonstrated anti-tumor activity, in
      particular in animal models of glioblastoma. Thus, clinical study CS10 with
      aprinocarsen was undertaken in patients with central nervous system (CNS)
      malignancies. The results of this study and considerations for future clinical
      studies in CNS tumors are reviewed.

PMID- 14719094
TI  - Elevated levels of angiostatin in effusions from patients with malignant disease.
AB  - The aim of this study was to determine the presence of angiostatin in ascitic and
      pleural effusions from cancer patients, as well as of metalloproteinases (MMPs)
      and urokinase-type plasminogen activator (uPA), both involved in angiostatin
      generation in in vitro models. Ascitic fluids, pleural exudates, and sera from 21
      cancer patients were analyzed for the presence of angiostatin by western blot,
      whereas gelatinases MMP-2 and MMP-9, and uPA were evaluated by zymography. Our
      study revealed elevated levels of angiostatin in effusions of cancer patients,
      contrasting with mostly intermediate levels in less than half of their sera, and
      undetectable levels in normal sera. Despite the observation of enhanced levels of
      HMW-uPA and MMP-2 in malignant effusions from cancer patients, their analysis in
      individual samples showed no association between angiostatin presence and the
      enzymes, suggesting that the latter would not play an unimportant role, if any,
      in in vivo generation of angiostatin.

PMID- 14719095
TI  - Increased mRNA expression of ADAMs in renal cell carcinoma and their association
      with clinical outcome.
AB  - ADAMs (a disintegrin and metalloproteinase) are cell-surface proteins with
      adhesion and protease activity which play important roles in many biological
      processes. Little is known about their role in cancer. The aim of the study was
      to assess the quantitative expression of the ADAMs in human renal cell carcinoma
      (RCC) and to associate expression levels with clinicopathological data. We
      investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2
      in paired tissue samples from cancerous and non-cancerous parts of the kidneys of
      27 patients with RCC who underwent tumour nephrectomy. Measurements were
      performed by means of the quantitative real-time RT-PCR on a LightCycler
      instrument. ADAM-8, -17, and -19 were significantly higher expressed (p<0.05 at
      least) in cancerous compared with the matched non-cancerous tissue in pT1 and >
      or =pT2 tumours, ADAM-28 and ADAM-TS2 only in pT1 tumours, and ADAM-TS1 was not
      differently expressed. All ADAMs except ADAM-TS1 showed an increase of expression
      in the non-cancerous tissue with rising pT stage suggesting an early involvement
      of ADAMs in the development of RCC. The expression of ADAM-8 was related to a
      shorter survival of patients and was the best predictor of distant metastases.
      Our results indicate a potential role for ADAMs in RCC and that the
      overexpression might be a useful predictive tool.

PMID- 14719096
TI  - Connexin 26 induces growth suppression, apoptosis and increased efficacy of
      doxorubicin in prostate cancer cells.
AB  - Connexin 26 (Cx26) encodes a gap junction protein and is a putative tumor
      suppressor gene. We evaluated the effect of forced expression of Cx26 on three
      human prostate cancer cell lines, PC-3, LNCap, and DU-145. The three cell lines
      were infected with a Cx26 adenovirus vector (Ad-Cx26) or a control vector or were
      mock infected. We tested cell growth, cell cycle, apoptosis, and the efficacy of
      combined treatment with doxorubicin. Ad-Cx26 infection suppressed the growth of
      all the cell lines compared with controls and induced cell cycle arrest at the
      G2/M phase and apoptosis. Ad-Cx26 decreased the expression of Bcl-2. LNCaP cell
      growth was dramatically suppressed by Ad-Cx26 alone. PC-3 and DU-145 had greater
      growth suppression with combined gene therapy and chemotherapy than with either
      Ad-Cx26 or doxorubicin alone. Forced expression of Cx26 suppresses the growth of
      prostate cancer cells and decreases the expression of Bcl-2. Combining Cx26 gene
      therapy with doxorubicin results in greater growth suppression.

PMID- 14719097
TI  - Selective prognostic impact of serum alpha-fetoprotein level in patients with
      hepatocellular carcinoma: analysis of 543 patients in a single center.
AB  - The prognostic impact of serum alpha-fetoprotein (AFP) level in patients with
      hepatocellular carcinoma (HCC) is controversial. This study aimed to investigate
      the predictive ability of serum AFP in HCC patients. A total of 543 patients
      undergoing surgical resection (258 patients) and non-surgical treatment (285
      patients) including transarterial chemoembolization and percutaneous injection
      therapy were retrospectively studied. Overall, AFP level >400 ng/ml was an
      independent poor prognostic predictor [relative risk (RR): 1.4, 95% confidence
      interval (CI): 1.0-1.9, p=0.049]. Stratified analysis showed that there was a
      sharp contrast of predictive power of AFP level in treatment strategy and tumor
      size. In surgical patients, serum AFP >400 ng/ml was a tumor size-independent
      predictor of tumor recurrence (RR: 1.7, 95% CI: 1.2-2.5, p=0.006) and survival
      (RR: 2.3, 95% CI: 1.3-3.8, p=0.002). However, there was no association between
      AFP level and survival in the non-surgical group (p=0.597). Alternatively, among
      the 157 patients with large (>5 cm) HCCs, AFP >400 ng/ml independently predicted
      a poor survival (RR: 1.9, 95% CI: 1.2-2.5, p=0.012), whereas no clear
      relationship between AFP level and survival was found among the 386 patients with
      small (< or =5 cm) HCCs (p=0.685). There was no differential prognostic impact of
      serum AFP levels in other variables. In conclusion, serum AFP level is a weak
      prognostic predictor in HCC patients. Its predictive ability is highly selective
      and dependent on treatment strategy and tumor size. Incorporation of serum AFP
      level into any prognostic prediction model should be based on its distinctive
      selective prognostic power.

PMID- 14719098
TI  - The expression and prognostic significance of HER-2 in colorectal cancer and its
      relationship with clinicopathological parameters.
AB  - The prognostic role of HER-2 has been established in breast cancer but remains
      controversial in colorectal cancer. In this study, 170 archival specimens of
      Dukes' B and C colorectal cancer were analysed immunohisto-chemically, using an
      anti-HER-2 monoclonal antibody HM64.13. Immunostaining was classified as
      cytoplasmic or membranous, and the intensity of the immunostaining was graded
      negative, weak or strong. The association between these scores and survival was
      estimated using Cox survival analyses. Overall, 87% of cases showed cytoplasmic
      HER-2 staining, with 54% exhibiting strong intensity cytoplasmic immunostaining.
      Membranous HER-2 was seen in 41% of cases, with most of these being of strong
      intensity. No correlation with clinical outcome was seen with membranous HER-2.
      Positive cytoplasmic immunostaining was found to be associated with a
      significantly better overall survival (HR 0.46, CI95 0.24-0.87) in the Dukes C
      cancers, but no survival benefit was seen in the Dukes' B cancers. Tumour grade,
      depth of tumour invasion and positive apical node were also found to be
      independent prognostic factors in Dukes' C cancers. We conclude that HER-2 over
      expression occurs in a significant number of colorectal cancers. Since
      cytoplasmic HER-2 is incapable of transmitting the strong mitogenic signal via
      heterodimerization with other members of the Epidermal Growth Factor Receptor
      (EGFR) family, this may partly explain the correlation between cytoplasmic HER-2
      over-expression and a better prognosis in the Dukes' C colorectal cancers. In
      addition, high levels of membraneous HER-2 in colorectal cancer could make HER-2
      a good target for monoclonal antibody-based immunotherapy.

PMID- 14719099
TI  - Altered p16INK4a and Fhit expression in carcinogenesis and progression of human
      oral cancer.
AB  - To further characterize the biological and clinical role of molecular alterations
      involved in oral squamous carcinogenesis, the immunohistochemical expression
      level of two tumor suppressor genes, fragile histidine triad and p16INK4a, in non
      carcinomatous squamous epithelia and head and neck squamous cell carcinoma was
      determined. In addition, human papillomavirus infection determined by PCR assay
      and the use of alcohol and cigarettes were evaluated. In this study 28 non
      carcinomatous squamous epithelia and 57 head and neck squamous cell carcinoma
      were considered. The expression levels of fragile histidine triad were lower in
      head and neck squamous cell carcinoma than in non-carcinomatous squamous
      epithelia. In contrast, p16INK4a is expressed in malignant lesions (51% of the
      cases analyzed), but not in non-carcinomatous squamous epithelia. No correlation
      between gene expression alterations of the two tumor suppressors was observed.
      PCR analysis showed that HPV DNA was present in 5 of the 57 malignant lesions
      analyzed (8.8%). None of the factors described above, despite changes in gene
      expression and HPV infection, appears to be associated with alcohol use and/or
      tobacco smoking and clinical outcome. Our data showed that fragile histidine
      triad and p16INK4a expression are altered in malignant lesions. Most likely, the
      decreasing levels of fragile histidine triad is directly involved in cancer
      development, while the accumulation of p16INK4a in head and neck squamous cell
      carcinoma may be the consequence of loss of functional tumor suppressor
      retinoblastoma pathway.

PMID- 14719100
TI  - Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma.
AB  - SOX2, a SRY-related HMG box protein, is thought to be an important transcription
      factor during organogenesis, including the stomach although the expression and
      function are unclear. We investigated SOX2 protein expression to clarify its
      roles in differentiation and carcinogenesis of the stomach. Using polyclonal SOX2
      antibodies, expression of SOX2 in gastric normal mucosae, intestinal metaplasia
      and carcinomas from 68 gastric carcinoma patients was studied by
      immuohistochemistry. SOX2 was strongly and moderately expressed in the nuclei of
      the foveolar epithelium and intestinal metaplasia, respectively, the expression
      being much higher than that in carcinomas (p<0.0001). Using antibodies to MUC5AC,
      MUC2 and CD10, the 68 gastric carcinomas were classified into gastric type,
      intestinal type, mixed gastric and intestinal type, and null type. A significant
      difference in SOX2 expression was observed between the gastric and intestinal
      types (p<0.05), with a higher expression in the former than in the latter.
      Moreover, over-expression of SOX2 induced the mRNA expression of endogenous
      MUC5AC, a specific mucin marker for the gastric type, in COS-7 cells. Our
      findings indicate that SOX2 may play a role in differentiation of the human
      gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis,
      particularly in the gastric type.

PMID- 14719101
TI  - Targeted inhibition of NMYC by peptide nucleic acid in N-myc amplified human
      neuroblastoma cells: cell-cycle inhibition with induction of neuronal cell
      differentiation and apoptosis.
AB  - We developed an antisense peptide nucleic acid (PNA) targeted against a unique
      sequence in the terminus of the 5'-UTR of N-myc, designed for selective
      inhibition of NMYC in neuroblastoma cells. Fluorescent microscopy showed carrier
      free delivery of the PNA to two human neuro-blastoma cell lines: GI-LI-N (N-myc
      amplified) and GI-CA-N (N-myc-unamplified). Only in the former, PNA treatment
      determined 70% cell-viability reduction (at 48 h). In N-myc-amplified GI-LI-N
      cells, the PNA determined NMYC-translation inhibition (Western blotting),
      accumulation of cells in G1, induction of differentiation and apoptosis.
      Selectivity of the PNA was demonstrated by altering three point mutations. These
      findings should encourage development of a PNA-based tumor-specific agent for
      neuroblastoma (or other neoplasms) with N-myc overexpression.

PMID- 14719102
TI  - Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic
      effects of 5-FU.
AB  - We investigated the role of cyclin A in the cytotoxic effect of 5-fluorouracil (5
      FU) on cancer cell lines. Experiments were performed using gastric cancer
      chemosensitive NUGC3, and chemoresistant NUGC3/5FU/L established by repeated
      exposure to 5-FU. 5-FU inhibited cell growth of NUGC3 in a dose-dependent manner.
      Low concentrations of 5-FU did not inhibit cell growth of NUGC3/5FU/L, while high
      concentrations slightly inhibited cell growth. Examination of the cell cycle
      pattern of NUGC3 cells showed accumulation at S-phase at 10 micro M and at G1-S
      phase at 100 micro M of 5-FU. Cell cycle pattern of NUGC3/5FU/L cells did not
      change 5-FU concentrations. 5-FU increased cyclin A mRNA level in NUGC3 cells but
      not NUGC3/5FU/L cells. In the presence of 100 micro M 5-FU, cyclin A protein
      level increased 2.6-fold in NUGC3 and 1.47-fold in NUGC3/5FU/L. 5-FU dose
      dependently increased the percentage of cyclin A-positive NUGC3 cells, but not
      NUGC3/5FU/L cells. The percentage of cyclin A-positive cells in other 5-FU
      sensitive esophageal, colon and gastric cancer cell lines (T.Tn, LOVO, DLD-1, MKN
      7), increased in the presence of 1 and 10 micro M 5-FU, while cyclin A-positive
      cells in 5-FU resitant hepatocellular and colon carcinoma cell lines (HCC50 and C
      1), did not increase with the same treatment. Our results indicate that the
      cytotoxic effects of 5-FU in human cancer cell lines correlate with cyclin A and
      it may be used as a predictive factor for chemotherapy response.

PMID- 14719103
TI  - Enlargement of thermal ablation zone by the combination of ethanol injection and
      radiofrequency ablation in excised bovine liver.
AB  - The efficacy of radiofrequency ablation (RFA) and RFA with concurrent ethanol
      injection (EI-RFA) was compared. RFA (3-cm-electrode) was applied to bovine liver
      using three types of RFA equipment; Radionics, RITA and Radio Therapeutics
      Corporation (RTC). For EI-RFA, 5 ml of 99.5% ethanol was injected around the
      electrode. A total number of 40 RFA and EI-RFA treatments were performed. We
      compared RFA with EI-RFA by examining the size, shape of ablation zone, treatment
      time, power, and needle tip temperature. Liver specimens were examined for
      pathological changes. EI-RFA produced a larger zone of ablation than RFA alone
      using Radionics and RITA (Radionics, 35.3+/-7.4 cm(3) vs 23.2+/-7.7 cm(3),
      p<0.05; RITA, 30.7+/-10.3 cm(3) vs 19.7+/-4.7 cm(3), p<0.05), corresponding to
      shortest diameters of coagulation zone (Radionics, 3.7+/-0.4 cm vs 3.0+/-0.4 cm,
      p<0.05; RITA, 3.8+/-0.4 cm vs 3.1+/-0.3 cm, p<0.01). However, a larger ablation
      zone was not seen with the RTC device. The ablated volume per energy and the
      ablated volume per current density administered were greater with EI-RFA than
      with RFA using Radionics (p<0.05). The shape of the ablated zone changed from
      ellipsoid to spherical with EI-RFA using Radionics. No pathological differences
      between RFA and EI-RFA samples were detected. For a given amount of energy and
      current administered, ethanol injection caused a better ablation effect, in terms
      of the size and shape of the ablated zone, than RFA with Radionics and RITA
      equipment.

PMID- 14719104
TI  - Expression of CD97 and CD55 in human medullary thyroid carcinomas.
AB  - The heterodimeric CD97 protein is a member of the EGF-TM7 family of class II
      seven-transmembrane (7TM) receptors of 75-90 kDa and structurally related to the
      secretin receptor family. CD97 is expressed on leucocytes, lymphocytes and in
      cells of the hematopoietic system. The precise role for CD97 is still unknown.
      The ubiquitously expressed CD55 (also known as decay accelerating factor, DAF)
      protects host cells from complement attack. In addition, CD55 is a
      bacterial/viral receptor and was identified as a ligand for CD97. Employing
      computer aided UV-laser microdissection CD97 and CD55 were investigated in C
      cells of non-neoplastic thyroid specimens (n=3) and in medullary thyroid
      carcinomas (n=54) by multiplex RT-PCR. Frozen sections of all tissues were
      investigated by immunohistochemistry. All non-malignant thyroid specimens
      expressed CD97 mRNA weakly and were devoid of immunoreactive CD97 protein.
      Transcripts for CD97 were detected in all 54 MTC tissue specimens and CD97 gene
      activity directly correlated with the histopathological stage of the MTC. CD97
      transcriptional activity was high in advanced stages of MTC such as pT3/4. pT1/2
      tumors with exclusive intrathyroidal growth revealed weak CD97 expression. CD55
      gene expression was significantly lower in normal C-cells than in tumor tissues
      and all MTC displayed strong and specific CD55 immunostaining. We did not observe
      a correlation between the expression of CD55 mRNA or protein, respectively, and
      pTNM classification. In summary, in the present study we have identified CD97 as
      a novel marker expressed in dedifferentiated neoplastic human thyroid C-cells.
      CD97 and CD55 may facilitate adhesion of C-cell carcinoma to surrounding surfaces
      which would result in rapid tumor cell spread.

PMID- 14719105
TI  - Characterization of p53 gene mutations in a Brazilian population with oral
      squamous cell carcinomas.
AB  - Mutations in the p53 tumor suppressor gene are present in approximately 50% of
      all human cancers. We sought to determine the frequency and type of p53 mutations
      in squamous cell carcinomas (SCC) of the oral cavity in a Brazilian population.
      To identify p53 mutations we used PCR-SSCP in tumor tissue microdissected from
      paraffin- embedded and from fresh-frozen sections followed by direct sequencing
      of SSCP bands with altered electrophoretic mobility. We identified p53 mutations
      in 40% of the human SCC analyzed. The mutations were of a broad spectrum, with a
      preponderance of G --> A and A --> G transitions with an apparent hotspot at the
      CpG dinucleotide at codon 290. Patient samples were stratified according to
      tobacco and alcohol consumption as well as by anatomic location of the tumor, and
      although trends did emerge, no statistically significant associations were
      obtained between the occurance of TP53 mutations and these lifestyle habits. We
      conclude that p53 mutations are common among oral cavity cancers in this
      population, and stress the significance of this study since it is the first
      analysis of p53 mutation in oral cancer in a southern Brazilian population.

PMID- 14719106
TI  - Genes associated with liver metastasis of colon cancer, identified by genome-wide
      cDNA microarray.
AB  - To uncover mechanisms underlying progression of colorectal carcinogenesis and to
      identify genes associated with liver metastasis, we analyzed expression profiles
      of 14 primary colorectal cancers (CRCs) with liver metastases, and compared them
      with profiles of 11 non-metastatic carcinomas and those of 9 adenomas of the
      colon. A hierarchical cluster analysis using data from a cDNA microarray
      containing 23,040 genes indicated that the cancers with metastasis had different
      expression profiles from those without metastasis, although a number of genes
      were commonly up-regulated in primary cancers of both categories. We documented
      54 genes that were frequently up-regulated and 375 that were frequently down
      regulated in primary tumors with metastases to liver, but not in tumors without
      metastasis. Subsequent quantitative PCR experiments confirmed that PRDX4, CKS2,
      MAGED2, and an EST (GenBank accession number BF696304) were expressed at
      significantly higher levels in tumors with metastasis. These data should
      contribute to a better understanding of the progression of colorectal tumors, and
      facilitate prediction of their metastatic potential.

PMID- 14719107
TI  - Induction of apoptosis by bleomycin in p53-null HL-60 leukemia cells.
AB  - The role of p53 in apoptosis and the contrasting p53 status in tumors prompted us
      to investigate the bleomycin-induced apoptosis in p53-null human leukemia HL-60
      cells (bleomycin at 160 microM for 7.5 h). Cells with apoptotic phenotype
      increased from 0.87% in controls to 9.40% in bleomycin-treated cells. Both the
      enzymes, caspase-3 and -8, were activated. Furthermore, the apoptotic phenotypes
      totally disappeared with zVAD-fmk, a caspase inhibitor. Besides, cytochrome c
      release from mitochondria happened simultaneously to apoptotic phenotypes,
      shrinkage of mitochondria but being independent of the mitochondrial permeability
      transition, since cyclosporine A and bongkrekic acid were inefficient on induced
      apoptosis. On the other hand, incubations with bleomycin (BLM) did not result in
      detectable changes in the expression of Bcl-2- and Bax-mRNA neither Bcl-2- or Bax
      proteins. In conclusion, we suggest that BLM can produce apoptosis independently
      of p53 through three mechanisms: i) at the nuclear level by its endonuclease
      activities; ii) at the cell membrane, by activating caspases; and iii) at the
      mitochondria by releasing cytochrome c. These results indicate that BLM-induced
      apoptosis in HL-60 cells results from the activation of a mitochondria-dependent
      caspase cascade which includes also the activation of the initiator caspase-8.

PMID- 14719108
TI  - Effect of curcuma on radiation-induced apoptosis in human cancer cells.
AB  - There have been considerable efforts to search for naturally occurring substances
      for the intervention of carcinogenesis. Many components from dietary or medicinal
      plants have been identified that possess substantial chemopreventive properties.
      Curcuma, a yellow pigment from Curcuma longa, exhibits anti-inflammatory,
      antitumor, and antioxidative properties. Although its precise mode of action has
      not been elucidated so far, studies have shown that chemopreventive action of
      curcuma might be due to its ability to induce apoptosis (programmed cell death)
      in cancer cells. This original study was conducted in order to estimate whether
      curcuma enhances the radiation sensitivity of cancer cells. For this purpose,
      curcuma (concentrations ranging from 0 to 200 microM) was applied to human cancer
      cell cultures (HeLa, K-562 and IM-9) with or without X-irradiation (doses
      comprised between 0 and 8 Gy). Cell proliferation was monitored by trypan blue
      exclusion. For the estimation of apoptosis, changes in cell morphology and flow
      cytometry analysis (DNA content and presence of the sub-G1 peak) were performed.
      Microscopic examination of the curcuma-treated cells (with concentrations above
      100 microM) showed a characteristic morphology of apoptosis. Furthermore, cells
      treated with curcuma exhibited a sub-G1 peak from which the magnitude was
      proportional to the concentration of curcuma. X-irradiation alone induced
      polyploidisation and apoptosis of the three cell lines, proportional to the doses
      of irradiation with a marked difference in radiation sensitivity between the cell
      lines (IM-9 < K-562 < HELA). However, when radiation and curcuma were applied
      together, our results showed that in HELA, K-562 and IM-9, curcuma showed a
      radiation sensitising effect only at the dose of 200 micro M. This result may
      open a perspective of synergical therapy at the condition to also address the
      intrinsic toxicity of curcuma on normal cells.

PMID- 14719109
TI  - Deletion in p16INK4a and loss of p16 expression in human skin primary and
      metastatic melanoma cells.
AB  - p16INK4a gene mapped at chromosome 9p21 region encodes a tumor suppressor protein
      p16 which is frequently inactivated in human cancers, including skin melanoma. In
      order to clarify the importance of p16 alterations in melanoma, we examined the
      deletions of p16INK4a and expression of p16 protein in eight unselected primary
      and metastatic melanoma cell lines from human skin melanomas. Normal skin
      melanocytes were used as controls. Deletions of entire exons in the p16INK4a gene
      were detected by PCR technique and expression of the p16 protein was examined by
      Western blotting and immunocytochemistry. Results showed that the fragments from
      exons 2A, 2C and 3 in p16INK4a gene were totally deleted in the metastatic
      melanoma cell line, FM28.7 and the fragment from exon 3 was deleted in the
      metastatic melanoma cell line, FM55M2. P16 protein was strongly expressed in two
      of the primary melanomas cell lines (FM55P and RaH3). The p16 protein was weakly
      expressed in one of the metastatic melanoma cell lines (FM55M1) and negative in
      the other metastasis (FM55M2) as compared to their matched primary melanoma cells
      (FM55P). The p16 protein was strongly expressed in normal skin melanocytes.
      Immunocytochemistry showed that p16 protein was mainly localized in the nuclei of
      the melanoma cells and normal melanocytes, if it was expressed. Deletions of
      p16INK4a gene was uncommon and loss of p16 protein expression was common event in
      melanoma, especially in the later stages of melanoma.

PMID- 14719110
TI  - Detection of a set of peptide vaccine candidates for use in HLA-A31+ epithelial
      cancer patients.
AB  - The molecular basis of host-tumor interaction in HLA-A31+ cancer patients has not
      been well understood. This lack of clarification is hampering the development of
      specific immunotherapies for these patients. This study aimed to identify a set
      of CTL-epitope peptides applicable for the specific immunotherapy of cancer
      patients with HLA-A31 allele. HLA-A31 allele is expressed in 5-10% of the world
      population, with the highest expression among Brazilian Amerinds (65%), and the
      lowest in the Eskimo population (0%). We report herein four cDNAs encoding CTL
      epitopes and 7 epitope peptides with the ability to induce HLA-A31-restricted
      CTLs cytotoxic to tumor cell lines in the peripheral blood mononuclear cells of
      HLA-A31+ cancer patients. These peptides might be useful for the development of a
      peptide-based immunotherapy for HLA-A31+ cancer patients.

PMID- 14719111
TI  - Differential impact of p16 inactivation by promoter methylation in non-small cell
      lung and colorectal cancer: clinical implications.
AB  - Inactivation of p16 has been reported as one of the more frequent events in human
      carcinogenesis. In order to contribute to the knowledge of the impact of p16
      silencing by promoter methylation, we have investigated p16 expression and
      inactivation of p16 by methylation in two of the major types of human cancer, non
      small cell lung cancer (NSCLC) and colorectal cancer (CRC). p16 expression was
      evaluated by Western blot, and p16 promoter methylation by a methylation-specific
      PCR procedure (MSP). Clinical correlations were established using the chi-square
      test, and distributions of disease-free survival (DFS) were estimated with the
      Kaplan-Meier method. Analyses for p16 revealed that 61.22% (60 of 98) of NSCLCs,
      and 32.9% (26 of 79) of CRCs here considered, lacked p16 expression. Moreover,
      36.7% (22/60) of the non-small cell lung tumours without p16 expression showed
      p16 promoter methylation, detecting a significant correlation between p16
      methylation and the histological subtype of squamous cell carcinomas (SCC)
      (P=0.04). With respect to CRCs, p16 promoter methylation was observed in 26.9% of
      tumours that lacked p16 expression (7/26), all tumours studied showing partial
      methylation. Survival studies demonstrated a clear correlation between p16
      negative expression and poor prognosis in NSCLC patients. Moreover, we found a
      trend toward poor clinical evolution in the group of patients with tumours
      showing total p16 methylation, in NSCLC, without statistically significant
      differences in CRC. In conclusion, our results indicate that p16 alterations
      constitute a major molecular abnormality in NSCLC with a considerable prognosis
      impact, promoter methylation being an important mechanism involved in p16
      silencing. In CRC, however, p16 promoter methylation could be considered as a
      less definitive molecular factor without prognostic implication, since partial
      methylation constitutes a prevalent mechanism.

PMID- 14719112
TI  - Identification and characterization of murine mHAUSP encoding a deubiquitinating
      enzyme that regulates the status of p53 ubiquitination.
AB  - Recently, it was discovered that herpesvirus-associated ubiquitin-specific
      protease (HAUSP) in human interacts with p53 protein, and removes the ubiquitin
      from ubiquitinated p53. Thus, human HAUSP stabilizes the status of p53, induces
      p53-dependent cell growth repression and apoptosis. In this study, we isolated
      and characterized a mouse orthologue of HAUSP, mHAUSP. The mHAUSP cDNA was cloned
      from mouse ES cells by RT-PCR. The open reading frame consists of 3,312 bp and
      encodes a predicted protein of 1,103 amino acids with a molecular weight of
      approximately 135 kDa. The N-terminal region contains the Cys, His, and Asp
      domains, which are highly conserved in all deubiquitinating enzymes. Northern
      blot analysis revealed that two transcripts were detected in various tissues,
      with strong expression in brain, lung, thymus, and testis. In vivo and in vitro
      deubiquitinating enzyme assays demonstrated that mHAUSP has deubiquitinating
      enzyme activity. The overexpression of mHAUSP reduces the amount of ubiquitinated
      p53, indicating that it functions as a deubiquitinating enzyme for p53.

PMID- 14719113
TI  - Effectiveness of Type I interferons in the treatment of multidrug resistant
      osteosarcoma cells.
AB  - P-glycoprotein overexpression is an important adverse prognostic marker for
      osteosarcoma (OS) patients, which is associated with higher risk for developing
      metastases as a consequence of the limited responsiveness to standard treatments
      of P-glycoprotein overexpressing OS cells. The use of cytokines has been
      advocated as a possible therapeutic approach to overcome multidrug resistance
      (MDR), being active on cell lines that are resistant to conventional drugs. In
      this study, we evaluated in vitro effects of interferons (IFNs) on MDR P
      glycoprotein overexpressing OS cells. Type I IFNs, but not IFNgamma, showed
      tangible inhibitory effects on OS cell growth, which were higher in MDR cell
      lines compared to parental cells. The higher sensitivity of P-glycoprotein
      overexpressing cells to Type I IFNs correlates with higher expression of the
      activator of the transcription (STAT)-2 and (STAT)-3, two intracellular mediators
      of the IFNalpha and IFNbeta signaling pathways, whereas no differences were
      observed with respect to the expression or activation of the Type I IFN receptor
      and STAT-1. Exposure of OS MDR cells to Type I IFN decreased the expression of P
      glycoprotein. This effect resulted in a significantly increased chemosensitivity
      of MDR cells to doxorubicin. Therefore, our data support the use of IFNalpha or
      IFNbeta in the treatment of osteosarcoma patients who overexpress P-glycoprotein
      in their primary tumors, and respond insufficiently to current therapeutic
      regimens.

PMID- 14719114
TI  - Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled
      to inhibition of in vitro tumour invasion.
AB  - Mononuclear ruthenium-dmso compounds showed interesting antimetastatic properties
      on experimental models of solid tumours. In line with the interesting results
      with multinuclear platinum complexes, which proved to overcome cisplatin
      resistance, we thought it worthwhile to test the pharmacological properties of
      some dinuclear ruthenium complexes to ascertain the possible advantages due to
      the introduction of a second metal centre over NAMI-A and its mononuclear
      analogues. These compounds belong to the general formula X2[[RuCl4(dmso-S)]2(mu
      L)] or [X][[RuCl4(dmso-S)](mu-L)[RuCl3(dmso-S)(dmso-O)]] where L is a nitrogen
      donor ligand (pyrazine; pyrimidine; 4,4'-bipyridine; 1,2-bis(4-pyridyl)ethane;
      1,2-bis(4-pyridyl) ethylene; 1,3-bis(4-pyridyl)propane) and X a counterion. We
      focused on parameters related to metastatic ability such as gelatinase activity,
      detected by zymography, and invasive potential, measured by means of a transwell
      chamber. These activities were correlated to the ability to inhibit tumour
      metastases in vivo. All dinuclear complexes, except compound D8
      ([NH4]2[[RuCl4(dmso-S)]2(mu-pyz]), decrease the number of tumour cells that cross
      a matrigel barrier, and inhibit MMP-9 gelatinolytic activity at concentrations
      lower than that of NAMI-A and of other mononuclear ruthenium complexes. In vivo
      compounds D5 (Na2[[RuCl4(dmso-S)]2(mu-ethylbipy)]) and D7 ([NH4][[RuCl4(dmso
      S)](mu-pyz)[RuCl3(dmso-S) (dmso-O)]]) show anti-metastasis activity, at two dose
      levels, with mild or null effect on primary tumour growth; compound D8 is the
      weakest active. All compounds tend to accumulate in liver and kidneys, rather
      than in tumour and lungs. However, compound D5, the most active in vitro on
      invasion and gelatinases and active in vivo on metastasis, is better concentrated
      in the lungs than compound D8 which is less active or inactive in vitro and in
      vivo. Histological analysis show liver, as well as kidney toxicities that limit
      in vivo activity. These data thus suggest dinuclear ruthenium complexes as
      promising anti-invasive agents for cancer treatment.

PMID- 14719115
TI  - Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma.
AB  - Radiofrequency ablation (RFA) therapy is of great significance in the treatment
      of hepatocellular carcinoma (HCC) or metastatic liver tumors. RFA is able to
      achieve widely coagulated necrosis in a few sessions without major complications.
      However, HCC cases exist that are resistant to RFA therapy for several reasons.
      In the present study, we performed injection of the mixture of ethanol and
      lipiodol (percutaneous ethanol-lipiodol injection therapy: PELIT) for HCCs that
      lacked clear visuality of the entire shape of the tumor by ultrasonography (US)
      or computed tomography (CT), or that were difficult to treat with RFA alone due
      to their locations in the liver or due to severe liver dysfunction of the
      patients. Local recurrence rates of HCC treated with PELIT were shown to be low
      in patients followed up for at least 4 months. In all patients treated with
      PELIT, lipiodol was accumulated in the entire region of the tumor after several
      trials of PELIT and the accumulation was kept for many months. The biopsy
      examination from the tumor treated with PELIT showed that HCC cells were totally
      destroyed by the PELIT. Although RFA therapy serves as a central role for the
      treatment of HCCs, PELIT, considered to be milder therapy, is likely to be
      important as a supportive treatment for HCCs and useful for the treatment of HCCs
      that are difficult to treat with RFA.

PMID- 14719116
TI  - Rationale for the use of gemcitabine in breast cancer (Review).
AB  - Many active cytotoxic drugs and several regimens exist for breast cancer therapy.
      However, these conventional treatments have not changed the outcome of patients
      with locally advanced and metastatic disease. As a consequence, the dynamic
      balance between chemotherapy-induced side effects and benefits attributable to
      relief of cancer-related symptoms must be carefully considered in this setting.
      Gemcitabine is a pyrimidine nucleoside antimetabolite that has shown activity in
      a variety of solid tumors, a good toxicity profile, and non-overlapping toxicity
      with other chemotherapeutic drugs. As a single agent, gemcitabine yields response
      rates ranging from 14 to 37% as first-line treatment for advanced breast cancer
      and 12-30% as salvage therapy for patients previously treated with anthracycline
      and/or taxane treatment. Combined with vinorelbine, platinum, anthracyclines, and
      taxanes as doublets or triplets, response rates of 50 to 80% have been reported
      in phase II clinical studies. Gemcitabine in combination with anthracyclines and
      taxanes has been evaluated in the neoadjuvant setting in patients with early
      stage breast cancer with interesting clinical and pathological response rates.
      Preliminary results of gemcitabine in combination with the biologic agent,
      trastuzumab, are encouraging. Phase III trials of gemcitabine combinations
      compared to standard regimens are ongoing with the aim to assess the independent
      contribution of gemcitabine.

PMID- 14719117
TI  - Effect of human chorionic gonadotropin in the gene expression profile of MCF-7
      cells.
AB  - The preventive effect of human chorionic gonadotropin (hCG)-induced
      differentiation on experimental mammary carcinogenesis has been reported to be
      due to the inhibition of cell proliferation, increased DNA repair capabilities of
      the mammary epithelium, decreased binding of the carcinogen to the DNA and
      activation of programmed cell death genes leading to apoptosis. To further our
      understanding of the molecular pathway of the hCG action on mammary epithelial
      cells we have analyzed gene expression profiles of MCF-7 cells treated with hCG
      for 24, 48, and 96 h, using a DNA microarray consisting of 1176 genes. Comparison
      of expression between the treated and not treated cells enabled us to identify 48
      genes that are affected by this hormone. Importantly, there is a cluster of genes
      that are overexpressed during the first 24 h and level off thereafter, whereas
      other genes are maximally expressed at 96 h of treatment. The results obtained in
      this study demonstrated that genes regulating cell proliferation, apoptosis, cell
      trafficking, and DNA repair are significantly affected by hCG in human breast
      cancer cells in vitro.

PMID- 14719118
TI  - Differential activation of the Fas/CD95 pathway by Ad-p53 in human gliomas.
AB  - Adenoviral p53 gene transfer (Ad-p53) induces apoptosis in glioma cells
      expressing mutant p53, but fails in cells with wild-type p53. Endogenously,
      gliomas express varied levels of Fas/CD95, yet constitutively high levels of
      Fas/CD95 ligand. Because the mechanism behind the differential apoptotic response
      to Ad-p53 infection remains elusive, we examined how the Fas/CD95 pathway is
      involved in U87MG (wt-p53), D54 (wt-p53), U251MG (mutant-p53), and U373MG (mutant
      p53) glioma cell lines. Ad-p53 infection did not alter the levels of Fas/CD95
      ligand in either wild-type or mutant p53-expressing cell lines. In contrast, Ad
      p53 infection led to an approximately 3-fold increase in Fas/CD95 mRNA expression
      in mutant p53-bearing cell lines but not in their wild-type (wt) counterparts, as
      assessed in an RNase protection assay. Fas/CD95 mRNA induction appeared to be
      regulated at the transcriptional level because Ad-p53 infection resulted in up to
      a 4-fold increase in Fas/CD95 promoter reporter activity. Subsequently, flow
      cytometric analysis revealed a 2- to 4-fold increase in surface Fas/CD95
      expression following Ad-p53 infection in mutant-p53-containing cell lines. Use of
      the protein transport inhibitor Brefeldin A significantly inhibited Ad-p53
      induced surface Fas/CD95 expression, but only partially inhibited apoptosis in
      mutant-p53 cell lines. These results suggest that p53 regulates Fas/CD95
      expression at the transcriptional level and through protein trafficking in mutant
      p53 cell lines. Fluorogenic activity assays demonstrated that induction of
      caspase-8 activity following Ad-p53 infection correlated with increases in
      Fas/CD95 expression. Incubating cells with a caspase-8-specific inhibitor Ac-IETD
      CHO prior to Ad-p53 infection inhibited caspase-8 activity and apoptosis.
      Together, our results suggest that regulation of the Fas/CD95 pathway is partly
      responsible for Ad-p53-induced apoptosis in glioma cells, which depends on the
      p53 status of the involved cells. Additionally, the inability of Ad-p53 to
      activate the Fas/CD95 pathway in wt-p53 glioma cells coincides with their
      apoptotic-resistant phenotype. Further elucidation of the nature of this
      resistance could ultimately augment the efficacy of Ad-p53 gene therapy.

PMID- 14719119
TI  - Effects of extracts from Bangladeshi medicinal plants on in vitro proliferation
      of human breast cancer cell lines and expression of estrogen receptor alpha gene.
AB  - In this study we determined the activity of extracts from Bangladeshi medicinal
      plants (Emblica officinalis, Aegle marmelos, Vernonia anthelmintica, Oroxylum
      indicum, Argemone mexicana) on human breast tumor cell lines. Extracts from E.
      officinalis and O. indicum displayed anti-proliferative activity on MCF7 and MDA
      MB-231 breast cancer cell lines, while extracts from A. mexicana were active on
      MCF7 cells, exhibiting on the contrary low antiproliferative effects on MDA-MB
      231 cells. Extracts from A. marmelos and V. anthelmintica were antiproliferative
      on both cell lines, but at higher concentrations. The accumulation of estrogen
      receptor alpha (ERalpha) mRNA, a marker of neoplastic status, was analysed by
      quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The data
      obtained demonstrated that only extracts from E. officinalis induce an increase
      of ERalpha mRNA in MCF7 cells. When MDA-MB-231 cell line was employed, extracts
      from E. officinalis, V. anthelmintica and A. mexicana were found to be inducers
      of the increase of ERalpha mRNA accumulation. Since activation of ERalpha gene
      expression could have clinical impact, our results suggest a possible use of
      extracts from medicinal plants to identify compounds of possible interest in the
      treatment of breast cancer.

PMID- 14719120
TI  - Establishment and some characteristics of epoxomicin (a proteasome inhibitor)
      resistant variants of the human squamous cell carcinoma cell line, A431.
AB  - A431 resistant variants to epoxomicin (EXM) were established, showing 4.0-6.7
      times more resistance to EXM than parental A431P. Both variants demonstrated
      increased expression of the beta-subunit molecules of 26S proteasome with
      approximately 2.5 times increased activity. In variant cells, cyclin B and
      P34cdc2 were over-expressed, whereas P21WAF1 was expressed at a similar level to
      A431P. Because of the proteasome inhibitor acting as a G2/M blocker, results are
      to the advantage of resistant cells proliferating in the presence of an inhibitor
      under a severe environment. Variant cells showed increased expression of
      epidermal growth factor receptor (EGFR) and decreased expression of mRNA, but
      also slight accumulation of protein of c-Cbl, which is a negative regulator of
      EGFR possessing ubiquitin ligase activity to desensitize EGF signaling. UbcH7,
      acting intimately with c-Cbl, was decreased in level compared to A431P. These
      phenomena can be regarded as one of the causes of prevention of c-Cbl-mediated
      down-regulation of EGFR in variant cells, enabling them to live. The anti
      apoptotic Bcl-2 mainly consisted of a phosphorylated form with resistance to
      proteasomal degradation, suggesting that Bcl-2 phosphorylation occurred
      independently of its apoptotic function. Variant cells showed resistance not only
      to EXM, but to the 5 proteasome inhibitors, while demonstrating collateral
      sensitivity to doxorubicin.

PMID- 14719121
TI  - Mutation and aberrant expression of Caveolin-1 in human oral squamous cell
      carcinomas and oral cancer cell lines.
AB  - Caveolin-1, a tumor suppressor gene, was found to be inactivated by structural
      abnormalities or epigenetic changes in several types of human cancers. In order
      to investigate the role of Caveolin-1 in the pathogenesis of human oral squamous
      cell carcinoma, the exon 1 and 3 sequences of the Caveolin-1 were investigated in
      74 oral squamous cell carcinomas and 15 oral cancer cell lines. In addition,
      Caveolin-1 expression was examined in 15 oral cancer cell lines. Mutations of the
      Caveolin-1 gene were identified in five cancers (1 missense and 4 silent
      mutations), with all mutations being detected in exon 3. Among the cancers
      containing the Caveolin-1 mutation, case 53 harbored a missense mutation from Ile
      (ATT) to Phe (TTT) at codon 141 and two silent mutations at codons 112 and 163 of
      the Caveolin-1 gene. Cases 27, 44, and 84 had two silent mutations from GAC (Asp)
      to GAT (Asp) at codon 82, and from CCA (Pro) to CCT (Pro) at codon 132. Case 89
      contained three silent mutations at codons 84, 124, and 161. However, mutations
      of the Caveolin-1 gene were not observed in normal human oral keratinocytes, the
      human papillomavirus-immortalized oral keratinocytes, and 15 oral cancer cell
      lines. Despite the intact Caveolin-1 gene, one oral cancer cell line, HEp-2,
      lacked the caveolin-1 protein. In contrast, two cancer cell lines, KOSCC-25C and 
      33B, had an insignificant amount of the caveolin-1 protein. These results provide
      genetic evidence showing that the inactivation of Caveolin-1 by a mutation or by
      reduced expression may play a role in the pathogenesis of oral cancer.

PMID- 14719122
TI  - Clinical value of alterations in p73 gene, related to p53 at 1p36, in human
      hepatocellular carcinoma.
AB  - A novel gene, p73, encoding a protein with significant homology to p53 and
      showing functional similarities to p53, was identified at chromosome 1p36, at
      which tumor suppressor gene of hepatocellular carcinoma (HCC) is supposed to be.
      Involvement of p73 in hepatocarcinogenesis is controversial and clinical value of
      p73 alterations remains obscure. We investigated allelic status of p73 in 63
      patients with HCC. Loss of heterozygosity (LOH) in p73 was analyzed by PCR-RFLP
      analysis. The results were compared with LOH on chromosome 1p surrounding p73
      locus, mutations of p53 and p73, and clinicopathologic characteristics. LOH on
      p73 was observed in 33% of informative tumors. LOH in p73 was not always observed
      between the regions with LOH on chromosome 1p examined despite the significant
      association of LOH in p73 with LOH on chromosome 1p. No mutations were detected
      in p73. Tumors with LOH in p73 were more frequently detected in liver without
      cirrhosis than that with cirrhosis. There was no significant statistic
      association between the presence of LOH in p73 and six different
      clinicopathologic characteristics such as age, sex, histological type, T stage,
      tumor diameter, and virus status. Disease-free survival rates of the patients
      with LOH in p73 were significantly poorer than those without LOH in p73.
      Multivariate analysis indicated that presence of LOH in p73 was independent
      prognostic factor in patients with HCC. These findings suggested that p73 might
      play some role in tumor progression of HCC even though p73 should not be
      considered a candidate gene on chromosome 1p of HCC and does not function as a
      tumor suppressor gene like p53. Identifying the patients with LOH of p73 in
      tumors could be useful to predict early recurrence and to stratify the patients
      who need adjuvant therapy after operation.

PMID- 14719123
TI  - Human B lymphoblast cell lines defective of Stat6 signaling produce high levels
      of proinflammatory cytokines IL-12, TNFalpha and IFNgamma.
AB  - Based on Stat6 gene knockout animal models, the Stat6 signaling pathway has been
      suggested to play a role in carcinogenesis and Th1/Th2 cytokine balance. Using a
      semiquantitative EMSA assay and EBV-transformed human B lymphoblast cell lines,
      we have previously identified three Stat6 activational phenotypes, termed as
      Stat6high, Stat6low, and Stat6null. A genetic mechanism has been proposed which
      determines the IL-4-induced activation of the human Stat6 signaling. With respect
      to the contribution of variant phenotypes to human disease, we further
      hypothesize that the Stat6null phenotype may result from a partial defect in
      Stat6 signaling which resembles Stat6 knockout animals in several functional
      aspects. The characterization of the human Stat6null phenotype stably displayed
      by the EBV-B cell lines is easily assailable and possesses important implications
      with respect to Th1/Th2 cytokine imbalance in diseases such as cancer
      development/metastasis and inflammatory diseases. In this study, we have extended
      our investigation to the downstream regulatory consequences associated with these
      Stat6 phenotypes. Production of three important proinflammatory cytokines, IL-12,
      TNFalpha and IFNgamma was examined in spontaneous EBV-B cell culture using ELISA
      methodology. Individual cell lines defined as Stat6null produced significantly
      higher levels of IL-12, TNFalpha and IFNgamma on day 4 in spontaneous culture in
      comparison with cell lines characterized as Stat6high and Stat6low. These
      observations of the human Stat6null phenotype, together with those accruing from
      Stat6 knockout mouse model studies, suggest that the Stat6 signaling pathway may
      play a role in maintaining the Th1/Th2 cytokine balance by directly and
      indirectly down-regulating the production of proinflammatory cytokines, a
      regulatory process which appears to go awry in inflammatory diseases. Moreover,
      observations from signal transduction studies in our human B lymphocyte model may
      be compatible with those in the chosen mouse B lymphocyte for establishing
      signaling networks by the Alliance for Cellular Signaling (AfCS).

PMID- 14719124
TI  - Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine
      in human and mouse dendritic cells.
AB  - Dendritic cells (DC) are specialized antigen presenting cells characterized by
      their ability to migrate into target sites and secondary lymphoid organs in order
      to process antigens and activate naive T cells. Previously, we have shown that
      several secretion products from platelets and mast cells such as histamine,
      sphingosine-1-phosphate (S1P), and lysophosphatidic acid (LPA) have chemotactic
      activity towards immature human DC. Furthermore, they limit the capacity of
      mature human DC to initiate and amplify T helper cell type 1 (Th1) immune
      responses by inhibition of interleukin (IL)-12 and upregulation of IL-10
      secretion. In this study we focused on the effect of these agents on murine DC.
      In murine DC no influence on IL-10 and IL-12 release by these agents was
      observed. Moreover, histamine and LPA failed to stimulate chemotaxis and actin
      reorganization in mouse DC. Instead, S1P had chemotactic activity and induced
      actin polymerization in immature as well as mature mouse DC. Therefore, our in
      vitro data implicate that in contrast to humans the function and immunological
      capacity of murine DC are not so tightly controlled by mast cell and platelet
      derived secretion products such as histamine, S1P and LPA. These findings suggest
      that mouse models might underestimate the complex regulative network between mast
      cells, platelets and DC.

PMID- 14719125
TI  - Proliferation of D2-40-expressing intestinal lymphatic vessels in the lamina
      propria in inflammatory bowel disease.
AB  - Lymphatic vessels in the colon are normally distributed beneath the muscularis
      mucosae with rare branches reaching through the muscularis mucosae to the most
      basal aspect of the colonic crypts. In chronic inflammatory bowel disease
      demonstrating acute inflammation and architectural disarray, lymph vessel
      proliferation is seen within the lamina propria and within the submucosa. We
      analyzed the number and distribution of lymphatic vessels within the lamina
      propria and submucosa in chronic active and treated ulcerative colitis with
      restoration of architecture by immunostaining with D2-40, a specific monoclonal
      antibody against lymphatic vessels. We found significantly increased numbers of
      lymph vessels in chronic active ulcerative colitis both within the lamina propria
      and the submucosa as compared to normal mucosa. Numbers of lymph vessels in
      lamina propria were highest in severe chronic active ulcerative colitis and less
      in moderate and minimal residual disease with minimal architectural disarray
      (p<0.05). Lymph vessels in the submucosa were increased significantly above
      normal values in both severe, moderate and minimal residual disease. We conclude
      that lymph vessel distribution in chronic active ulcerative colitis extends into
      the lamina propria. With restoration of architectural morphology, the integrity
      of the lamina propria in regards to the distribution of lymph vessels is
      restored.

PMID- 14719126
TI  - Expression of the beacon gene in the rat adrenal gland: direct inhibitory effect
      of beacon[47-73] on aldosterone secretion from dispersed adrenal zona glomerulosa
      cells.
AB  - Beacon gene was recently identified in the rat hypothalamus, and there is
      evidence that beacon may be involved in the functional regulation of
      neuroendocrine axes. Reverse transcription-polymerase chain reaction and
      immunocytochemistry showed the expression of beacon mRNA and protein in the rat
      adrenal gland, especially in the cortex. Beacon[47-73], at a concentration over
      10(-7) M decreased basal aldosterone secretion from dispersed rat zona
      glomerulosa (ZG) cells, without affecting the ACTH-stimulated one. Basal and
      agonist-stimulated corticosterone secretion from dispersed zona fasciculata
      reticularis cells and catecholamine release from adrenomedullary slices were
      unaffected by beacon[47-73]. The suppressive effect of beacon[47-73] on
      aldosterone secretion from ZG cells was abolished by either H-89 or calphostin-C,
      which are inhibitors of protein kinase A and C signaling cascades. Taken
      together, these findings allow us to suggest that beacon can be included in the
      group of regulatory peptides involved in the fine tuning of ZG secretory
      activity.

PMID- 14719127
TI  - Potential role of Helicobacter pylori in hepatocarcinogenesis.
AB  - Helicobacter species can induce carcinoma in the liver of certain mice.
      Furthermore, Helicobacter pylori (H. pylori) exhibits hepatotoxicity in vitro.
      These reports indicate that H. pylori may play a role in hepatocarcinogenesis.
      The aim of this study was to assess the presence of H. pylori in human
      hepatocellular carcinoma (HCC) to determine if H. pylori may affect the
      development of this disease. Liver specimens from 15 HCC patients dissected into
      tumor and non-tumor tissues were examined for H. pylori by PCR using two sets of
      primers for 16S rRNA and urease B. DNA sequencing analysis was performed to
      confirm that PCR products with 16S rRNA primers were derived from H. pylori DNA.
      The specimens were also examined for H. pylori by immunohistochemistry using anti
      H. pylori antibody. H. pylori was found in 13 of 15 tumor tissues, not in the non
      tumor tissues. By contrast, Escherichia coli and Bacteroides fragilis, frequent
      colonizers of gut, were not detected by PCR in the HCC tumors. Ten cirrhotic
      liver tissue specimens and seven normal liver tissue specimens were also negative
      for H. pylori DNA by PCR. The nucleotide sequence of the amplified fragment
      shared 100% identity with the 16S rRNA gene of H. pylori. H. pylori was also
      detected in HCC tissue by immunohistochemical analysis. The presence of H. pylori
      in human HCC tissue was demonstrated by PCR and immunohistochemical analysis.
      These findings suggest that H. pylori might contribute to the development of HCC.
      Further study is needed to prove the pathogenetic role of H. pylori in the
      development of human HCC.

PMID- 14719128
TI  - Study of cyclooxygenase-2 in renal cell carcinoma.
AB  - Cyclooxygenase (COX)-2 plays an important role in the development of various
      cancers due to its angiogenetic function. As the expression of COX-2 is up
      regulated in human colorectal carcinoma and other cancers, we investigated the
      expression of COX-2 in human renal cell carcinoma (RCC) tissues. One hundred and
      eight specimens were obtained from patients with RCC, and 20 from normal kidney
      (NK) tissues. Immunohistochemistry, using affinity purified anti-bodies against
      human COX-2, and RT-PCR to study the COX-2 mRNA expression were carried out. We
      also examined whether or not there was a significant difference in the expression
      of COX-2 among grades (G1, G2, G3) and stages (pT1, pT2, pT3a, pT3b) in RCC.
      While no marked expression of COX-2 was observed in the NK tissues, a
      significantly strong expression of COX-2 was detected in RCC tissues. The extent
      and intensity of immunoreactive COX-2 polypeptides in cancer cells were
      statistically greater than those of cells from normal kidney tissues. However, no
      marked difference was seen among grades or between stages. These results
      demonstrate that the generated COX-2 in human renal cell carcinoma plays an
      important role in the proliferation of malignant renal cells.

PMID- 14719129
TI  - pEYFP-Nuc vector is a useful tool for three-dimensional and time-lapse
      observation of nuclear morphology of Jurkat cells during apoptosis.
AB  - Using a pEYFP-Nuc vector, which contains nucleic acid sequences of a nuclear
      localization signal, we established a Jurkat-YN cell line that expressed enhanced
      yellow fluorescent protein (EYFP) in the nucleus. We observed three-dimensional
      and time-lapse changes in nuclear morphology of Jurkat-YN cells during Fas
      induced apoptosis using a confocal laser scanning microscope. The nuclear forms
      visualized by EYFP were almost equal in quality to those visualized by SYTO59, a
      nucleic acid stain for living cells. Three-dimensional deformities in the nuclear
      form were observed during apoptosis before chromatin condensation became
      apparent, indicating these deformities are characteristic morphological changes
      of the early stage of apoptosis. In conclusion, the pEYFP-Nuc vector is a useful
      tool in the time-lapse observation of nuclear morphology of living cells during
      apoptosis.

PMID- 14719130
TI  - Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of
      coronary heart disease.
AB  - Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the
      covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to
      apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk
      factor for coronary heart disease (CHD) and have been shown to be related with a
      familial clustering of ischemic cardiac events. Nevertheless, the association
      between apolipoprotein(a) isoforms and a positive familial history of CHD has
      received far less attention. In this report, we explored the distribution of
      apo(a) phenotypes in 127 CHD subjects with a family history of coronary events
      and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were
      detected by a high-resolution immunoblotting method. In univariate analysis, the
      percentage of subjects with at least one small sized apo(a) isoform was
      significantly higher in CHD patients with a positive family history than in those
      without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low
      molecular weight were the best predictors of familial aggregation of cardiac
      ischemia. We conclude that apo(a) size polymorphism is strongly associated with a
      familial history of CHD and is more efficient than Lp(a) plasma concentrations in
      predicting the familial clustering of coronary disease. When detected by high
      resolution techniques, apo(a) phenotypes are objective laboratory markers that
      can substitute for a knowledge of a positive family history of CHD and should be
      used, together with Lp(a) levels, to better assess the familial predisposition to
      coronary events.

PMID- 14719131
TI  - An optimal dosing schedule for a novel combination antimetabolite, TAS-102, based
      on its intracellular metabolism and its incorporation into DNA.
AB  - TAS-102 is a combination drug consisting of alpha,alpha,alpha-trifluorothymidine
      (FTD) and thymidine phosphorylase inhibitor (TPI). FTD is converted to F3TMP by
      thymidine kinase and inhibits the thymidylate synthetase (TS) activity by binding
      to TS. In addition, FTD triphosphate form, F3TTP is incorporated into DNA, which
      leads to cytocidal effects. Therefore, the incorporation of FTD into DNA is
      expected to be an important factor, discriminating it from 5-FU showing TS
      inhibitory activity as their main mechanism of action. To assess a clinically
      more effective regimen protocol, the intracellular metabolism and the
      incorporation of FTD into DNA were investigated using human cancer cell lines in
      vitro and in vivo. FTD was incorporated into DNA in a time-dependent manner, but
      not in a concentration-dependent manner. FTD was the most efficiently
      incorporated into DNA after treatment with a several-micro molar level of FTD for
      around 8 h. The intracellular F3TTP was rapidly eliminated from tumor cells, as
      soon as FTD was washed out from the culture medium, whereas the FTD incorporated
      into DNA was retained by 80% or more even at 24 h after a washing-out procedure.
      When TAS-102 was administered into tumor-bearing mice once daily or three times
      daily at 3-h intervals at a dose of 150 mg/kg/day for one or 3 consecutive days,
      incorporation of FTD into tumor DNA by divided dosing significantly higher than
      that of single dosing. Based on our findings, the antitumor effects of TAS-102
      against 3 different human cancer cell xenografts into mice were examined. The
      divided daily dosing resulted in enhancement of the antitumor effects of TAS-102
      without any additional side effects. It is concluded that multiple daily dosing
      may result in better clinical benefits of TAS-102, when compared with single
      daily dosing and TAS-102 is a promising candidate for not only FU-sensitive but
      also FU-resistant cancer patients.

PMID- 14719132
TI  - A cohort study of chronic liver disease in an HCV hyperendemic area of Japan: a
      prospective analysis for 12 years.
AB  - A mass screening in 1990 of H town in Japan demonstrated a high prevalence of
      hepatitis C virus (HCV) infection in our previous studies. The purpose of the
      present study was to evaluate the prognosis and natural history of liver disease
      among the same residents after 12 years. Of 509 residents, 69 people had died,
      and 55 people had moved to other regions. In all, 139 persons of the remaining
      385 residing in H town were examined for liver function tests, antibodies to HCV
      (anti-HCV), serum HCV RNA, and hepatitis B virus surface antigen (HBsAg). The
      data of 14 of these 385 people were collected from medical records. The cause of
      death of the 69 individuals was investigated. The prognosis of liver disease
      could be clarified after 12 years in 222 of the 509 residents. Most of the
      residents with liver disease had an advanced stage of disease. Of the 69 persons
      who died, the mortality rate caused by liver cirrhosis or hepatocellular
      carcinoma (HCC) was 44 and 53%, respectively, among 25 persons with positive anti
      HCV, and 19 with positive HCV RNA. One person with positive HBsAg died of HCC.
      Persons with chronic HCV or HBV infection had significantly higher mortality
      rates from liver cirrhosis and HCC than those without infection (P<0.00001). The
      present study suggests that early detection and treatment for HCC should be
      carried out as HCV carriers age. Furthermore, persistent HCV carriers should
      receive therapy for suppression of the development of HCC. The eradication of HCC
      should be considered a national goal.

PMID- 14719133
TI  - Expression of IL-18 in patients with head and neck squamous cell carcinoma.
AB  - Interleukin-18 (IL-18), a recently described cytokine secreted mainly by
      macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer
      cells and T cells. The purpose of this study was to determine tissue expression
      and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to
      evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with
      primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50
      mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h.
      Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA,
      IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN
      gamma, and endotoxin plasma levels were also determined. Statistical analysis
      involved Welch t-test and Page's test for trend. The majority of patients with
      HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of
      these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level
      in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN
      gamma were not increased in patients. Endotoxin was not detectable in either
      group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and
      controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL
      18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS
      stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the
      response of PBMC to ethanol and LPS was similar in patients and controls. Our
      data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients,
      irrespective of its biological activity, suggest that serum IL-18 might be a
      candidate for a new marker for HNSCC. The pathways for IL-18 production and its
      mechanisms of action in patients with HNSCC remain to be determined.
      Understanding of the immunological pathways might offer new therapeutic options
      in head and neck cancer in the future.

PMID- 14719134
TI  - DNA copy-number analysis of the 22q11 deletion-syndrome region using array-CGH
      with genomic and PCR-based targets.
AB  - Deletions and duplications of genomic segments commonly cause developmental
      disorders. The resolution and efficiency in diagnosing such gene-dosage
      alterations can be drastically increased using microarray-based comparative
      genomic hybridization (array-CGH). However, array-CGH currently relies on
      spotting genomic clones as targets, which confers severe limitations to the
      approach including resolution of analysis and reliable gene-dosage assessment of
      regions with high content of redundant sequences. To improve the methodology for
      analysis, we compared the use of genomic clones, repeat-free pools of amplified
      genomic DNA and cDNAs (single and pooled) as targets on the array. For this
      purpose, we chose q11.2 locus on chromosome 22 as a testing ground.
      Microdeletions at 22q11 cause birth defects collectively described as the
      DiGeorge/velocardiofacial syndrome. The majority of patients present 3 Mb typical
      deletions. Here, we report the construction of a gene-dosage array, covering 6 Mb
      of 22q11 and including the typically deleted region. We hybridized DNA from six
      DiGeorge syndrome patients to the array, and show that as little as 11.5 kb non
      redundant, repeat-free PCR-generated sequence can be used for reliable detection
      of hemizygous deletions. By extrapolation, this would allow analysis of the
      genome with an average resolution of 25 kb. In the case of cDNAs our results
      indicate that 3.5 kb sequence is necessary for accurate identification of
      haploid/diploid dosage alterations. Thus, for regions rich in redundant sequences
      and repeats, such as 22q11, a specifically tailored array-CGH approach is good
      for gene copy number profiling.

PMID- 14719135
TI  - Quantitative analysis of gene expression in human articular chondrocytes in
      monolayer culture.
AB  - Human articular chondrocytes (HACs) were isolated from cartilage samples of
      normal joints and cultivated in monolayer for 56 days. Collagen type I, II, IX,
      aggrecan, and versican expression was quantified by real-time polymerase chain
      reaction (PCR). The expression of the genes was highly time-dependent and changed
      over the culture time. Collagen type I was not present at the beginning of the
      culture and increased 100-fold during the culture time. Collagen type II and IX
      expression was found during the entire culture period and decreased more than 100
      fold. Aggrecan expression was downregulated 100-fold whereas versican expression
      increased 10 times. Indices of cell differentiation, defined as ratios of
      collagen type II to I (CII/I), collagen type IX to I (CIX/I), and aggrecan to
      versican (Agg/Ver), were significantly higher at the beginning of the culture and
      decreased over the culture period. The CII/I and CIX/I ratios formed three
      phases, with a plateau at the beginning, followed by a transition phase and a
      steady state at the end of the culture time, whereas the Agg/Ver ratio declined
      constantly. The accurate quantitative assessment of extracellular matrix gene
      expression in samples of chondrocytes taken from monolayer culture can be used to
      monitor chondrocyte metabolism as well as changes in the cell differentiation
      status.

PMID- 14719136
TI  - Suppressive effect of regucalcin on protein phosphatase activity in the heart
      cytosol of normal and regucalcin transgenic rats.
AB  - The role of regucalcin, a regulatory protein in intracellular signaling pathway,
      in the regulation of protein phosphatase activity in the heart muscle cytosol was
      investigated by using normal (wild-type) and regucalcin transgenic (TG) rats.
      Protein phosphatase activity was assayed in a reaction mixture containing the
      cytosolic protein in the presence of phosphotyrosine, phosphoserine, and
      phosphothreonine. The addition of calcium chloride (10 and 20 microM) in the
      enzyme reaction mixture caused a significant increase in protein phosphatase
      activity toward three phosphoaminoacids. Trifluoperazine (10 and 20 microM), an
      antagonist of calmodulin, completely inhibited calcium (10 microM) addition
      increased protein phosphatase activity toward three phosphoaminoacids. Moreover,
      the calcium (10 microM)-increased enzyme activity toward phosphoserine and
      phosphothreonine was significantly enhanced by the addition of calmodulin (2.5 or
      5 microg/ml). Such an enhancement was not seen in the presence of
      phosphotyrosine. Regucalcin (10(-9) and 10(-8) M) significantly inhibited protein
      phosphatase activity toward three phosphoaminoacids in the presence of ethylene
      glycol bis (2-aminoethlether) N,N,N',N'-tetraacetic acid (EGTA; 1 mM), without
      Ca2+ addition. The inhibitory effect of regucalcin (10(-10)-10(-8) M) was also
      seen in the presence of calcium chloride (10 microM). Western blot analysis
      showed a remarkable expression of regucalcin protein in the cytosol of heart of
      regucalcin TG female rats as compared with that of wild-type female rats. Protein
      phosphatase activity toward three phosphoaminoacids was significantly decreased
      in the heart cytosol of TG rats. The enhancing effect of calcium (10 microM)
      addition on protein phosphatase activity toward three phosphoaminoacids was not
      seen in the heart cytosol of TG rats. This study demonstrates that endogenous
      regucalcin plays a suppressive role in the regulation of protein phosphatase
      activity in rat heart cytoplasm.

PMID- 14719137
TI  - Growth hormone secretagogue receptor subtypes 1a and 1b are expressed in the
      human adrenal cortex.
AB  - Ghrelin is an endogenous ligand of the growth hormone secretagogue receptors (GHS
      Rs), two subtypes of which have been recognized: the biologically active 1a and
      the biologically inactive 1b subtype. Reverse transcription-polymerase chain
      reaction demonstrated ghrelin and GHS-R1b mRNAs in eight human adrenal cortexes,
      and GHS-R1a mRNA only in six of the eight adrenal specimens. The GHS-R1a
      expression was absent in the two adrenal cortexes obtained from 76- and 79-year
      old male patients. Since previous studies showed that ghrelin does not affect
      steroid-hormone secretion, the present findings suggest that ghrelin via the GHS
      R1a could be involved in the autocrine-paracrine control of human-adrenal growth.

PMID- 14719138
TI  - Dynamic mutation and human disorders: the spinocerebellar ataxias (review).
AB  - A completely new mutational event associated with human diseases - the dynamic
      mutation - was discovered in the last decade. The molecular mechanism underlying
      dynamic mutation involves the expansion and intergenerational instability of a
      tandem-arrayed nucleotide sequence that acquire a pathological size, despite its
      polymorphic occurrence in normal individuals. To date, at least fourteen
      neurological disorders are associated with this phenomenon, including
      Huntington's disease (HD), dentatorubral and palidoluysian atrophy (DRPLA),
      spinobulbar and muscular atrophy (SBMA), myotonic dystrophy (DM), fragile X
      syndrome, FRAXE mental retardation and spinocerebellar ataxias (SCA) types 1-3, 6
      8, 12 and 17. The spinocerebellar ataxias comprise a heterogeneous group of
      severe neurodegenerative-late onset disorders characterized by loss of balance
      and coordination. Most of the spinocerebellar ataxias exhibit an autosomal
      dominant pattern of inheritance and are promoted by the intergenerational
      expansion of a trinucleotide repeat (CAG)n inside the coding region of the
      respective gene. The expanded segment is translated into an abnormal
      polyglutamine tract in the protein, leading to the formation of nuclear
      aggregates that have been considered the basis of the pathogenesis in most of SCA
      types. One striking characteristic of these diseases is that the gene is
      expressed throughout the brain and also in other tissues but no pathological
      consequences are observed, despite the specific cellular degeneration. The
      characterization of the mutational event has led to the development of specific
      and sensitive molecular tests for direct DNA analysis, which allow confirmation
      of clinical diagnostic and an adequate therapeutic indication as well as genetic
      counseling.

PMID- 14719139
TI  - Measuring telomerase activity in various human tumors in routine histology and
      cytology.
AB  - The aim of this study was to investigate telomerase reactivation, to
      quantitatively measure the human telomerase reverse transcriptase (hTERT) content
      and telomerase activity level (TA) in routine histological and cytological
      samples, and to examine the relationship between these values and morphological
      factors. We analyzed 86 (35 cytological and 51 histological) lesions which were
      divided into four main groups: renal tumors, soft tissue tumors, bladder-urine
      and thyroid gland lesions. The relative expression of mRNA of hTERT was examined
      by real-time polymerase chain reaction (RT-PCR). Almost all of the renal cell
      carcinomas showed TA. In soft tissue tumors no correlation was seen between TA
      and histogenesis, aggressiveness and prognosis. Concerning cytological material a
      very good correlation was seen between TA and the benign or malignant nature of
      these tumors (92.3% specificity and 60% sensitivity). Our results indicated that
      TA can be used beside histology also in cytologic samples, for example in the
      preoperative differential diagnosis of the thyroid gland lesions and urine
      samples. Telomerase reactivation may not play an important role in tumorigenesis
      in STT. Useful observations can be made by concentrating not only on one group of
      diseases or localization but the unselected analysis of routine diagnostic cases
      can also be of help both in diagnosis and therapy.

PMID- 14719140
TI  - Different muscarinc receptors are involved in the proliferation of murine mammary
      adenocarcinoma cell lines.
AB  - We described that two different murine mammary adenocarcinoma cell lines, LM3 and
      LM2 constitutively expressed muscarinic acetylcholine receptors (mAchR). We here
      demonstrate, by competitive binding experiments with the tritiated muscarinic
      antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor
      cell lines. Concordantly immunoblotting assays indicate that mAchR exhibit the
      following order of expression: M2 > M4 > M3 > M1 >> M5 in both tumor cell lines.
      Activation of mAchR with carbachol (CARB) increased proliferation in both tumor
      cell lines in a concentration dependent manner. In LM3 cells CARB promoted
      proliferation via M3 receptor activation via inositol 1,4,5-triphosphate and
      nitric oxide production. CARB-induced LM2 cells proliferation needed both M2 and
      M1 receptor activation, promoting prostaglandin E2 liberation and arginase
      catabolism respectively, both of them involved in tumor cell growth.

PMID- 14719141
TI  - A novel inducible amplifier expression vector for high and controlled gene
      expression.
AB  - Safety and efficacy are both required for successful gene therapy. In this
      regard, our laboratory has created a novel expression system, pHi-Hot that
      combines inducible and amplifier strategies in one construct. In pHi-Hot, the
      first transcriptional unit contains an inducible heat shock protein (hsp70B)
      promoter controlling the expression of a transcriptional factor, Tat, which
      transactivates a second promoter, the HIV2 LTR, located downstream on the same
      construct. The second promoter drives the gene of interest. The magnitude of the
      amplified second gene expression can be regulated through manipulating the
      activity of the hsp promoter driving the Tat gene. Using the human interleukin-2
      (IL-2) cytokine gene as the reporter gene, we demonstrated that moderate heat
      shock at 42 degrees C for 30 min, the pHi-Hot vector could achieve high gene
      expression levels while maintaining its inducibility. The induced IL-2 levels
      were 35- to 70-fold higher than achieved by using the hsp promoter alone, and 10-
      to 35-fold higher than achieved by using the CMV promoter. Using inducible and
      amplifier strategies, we can achieve high and controlled gene expression levels
      from a single construct. Finally, we discuss the advantages of using these
      strategies in developing new targeting and inducible vectors for genetic research
      and gene therapy.

PMID- 14719142
TI  - Thrombin stimulates IL-6 and IL-8 expression in cytomegalovirus-infected human
      retinal pigment epithelial cells.
AB  - Recently, we reported that thrombin specifically stimulates protease-activated
      receptor-1 (PAR-1) signaling in RPE entailing inhibition of Sp1 dependent HCMV
      replication. We now studied whether thrombin modulates the expression of the
      proinflammatory cytokine/chemokines IL-6 and IL-8 in mock- and cytomegalovirus
      infected human retinal pigment epithelial cells (RPE). Our data show that
      thrombin/PAR-1 stimulates IL-6 and IL-8 gene transcription and protein secretion
      in both mock- and HCMV-infected RPE. Thrombin/PAR-1-mediated signaling stimulated
      PKC and NF-kappaB-dependent IL-6 and IL-8 gene expression via phosphoinositide 3
      kinase and further downstream via p42/44 and p38 MAPKs. Thus, thrombin/PAR-1
      mediated IL-6/IL-8 gene expression is uncoupled from Sp1 inhibition and may
      support proinflammatory pathomechanisms probably involved in hemorrhage/HCMV
      retinitis progression.

PMID- 14719143
TI  - Identification and characterization of human MPP7 gene and mouse Mpp7 gene in
      silico.
AB  - Drosophila Crumbs (Crb), Stardust (Sdt), Discs large (Dlg), Scribble (Scrib) and
      Lethal giant larvae (Lgl) are involved in the establishment and the maintenance
      of apicobasal polarity in epithelial tissues. Because epithelial polarity is
      disrupted in tumors, human homologs of Drosophila crb, sdt, dlg, scrib, and lgl
      are potential cancer-associated genes. MPP1/EMP55, MPP2, MPP3, MPP4, MPP5/PALS1
      and MPP6/PALS2 genes are human homologs of Drosoplila sdt. Here, we identified
      and characterized a novel member of MPP gene family, MPP7, by using
      bioinformatics. Uncharacterized FLJ32798 cDNAs (BC038105 and AK057360) were
      derived from human MPP7 gene. BC038105 was a representative MPP7 cDNA, while
      AK057360 was an aberrant MPP7 cDNA with a frame shift. Human MPP7 mRNA was
      expressed in placenta, brain, testis as well as in uterus tumor, bladder tumor,
      and lymphoma. Microsatellite marker D10S588, linked to IDDM and hereditary
      thrombocytopenia, was located within the MPP7 gene at human chromosome 10p12.1.
      Nucleotide sequence of mouse Mpp7 cDNA was determined in silico by assembling 3'
      truncated cDNA AK078849, genome clone RP24-255J24, and EST AV260217. Human MPP7
      showed 92.9% total-amino-acid identity with mouse Mpp7, and 75.7% total-amino
      acid identity with zebrafish humpback. MPP7 orthologs were MAGUK proteins with
      two L27 domains, PDZ domain, SH3 domain, and GuKc domain. MPP7 was most related
      to MPP3 among MPP family members, functioning as adopter molecules assembling Crb
      homologs (CRB1, CRB3), Dlt homologs (INADL/PATJ, MPDZ/MUPP1), and Lin-7 homologs
      (LIN7A, LIN7B, LIN7C). This is the first report on identification and
      characterization of human MPP7 and mouse Mpp7 genes.

PMID- 14719144
TI  - Functional outcome and quality of life after repeat ileal pouch-anal anastomosis
      for complications of ileoanal surgery.
AB  - PURPOSE: Disconnection of an ileal pouch-anal anastomosis with repeat ileal pouch
      anal anastomosis has been proposed for treatment of ileal pouch-anal anastomosis
      failure caused by septic or functional complications. We report our experience
      with repeat ileal pouch-anal anastomosis, and document functional outcome and
      quality of life. METHODS: Of 101 patients undergoing laparotomy, ileoanal
      disconnection, and repeat ileal pouch-anal anastomosis, 80 were referred from
      other institutions. Indications included: chronic anastomotic leak (n=27),
      perineal or pouch-vaginal fistula (n=47), anastomotic stricture (n=22),
      dysfunction/long efferent limb of S-pouch (n=36), and previous ileal pouch-anal
      anastomosis excision or exclusion (n=6). In 64 cases a "septic" indication was
      observed. Pathologic features of Crohn's disease were present in 4 patients
      preoperatively and 15 more after repeat ileal pouch-anal anastomosis. Four
      patients had clinical features of Crohn's disease. RESULTS: Three patients had no
      ileostomy, and 82 patients had temporary ileostomy closure. Of these, 82 percent
      have a functioning pouch, with a median follow-up of 32 functioning months. Two
      were rediverted and 13 had the pouch excised. Five-year pouch survival was 74
      percent, higher for ulcerative colitis (79 percent) than Crohn's disease (53
      percent; P=0.06). No differences were seen between those having repeat ileal
      pouch-anal anastomosis for septic or nonseptic indications, or whether using a
      new or repaired pouch. Patients defecated 6.3 +/- 2.8 (mean +/- standard
      deviation) times per day, and 2 +/- 1.9 per night. Thirty-five percent of
      patients never described urgency. Fecal seepage occurred in 50 percent during the
      day and 69 percent at night. Using the Cleveland Global Quality of Life Score to
      assess the patient's quality of life, health, level of energy, and happiness with
      surgery (each scored from 0-10), quality of life was 8.2 +/- 1.6, and happiness
      with surgery was 9 +/- 2. Ninety-seven percent would undergo repeat ileal pouch
      anal anastomosis again, and 99 percent would recommend it to others. CONCLUSIONS:
      Repeat ileal pouch-anal anastomosis is a valid alternative for patients with
      ileal pouch-anal anastomosis failure. A controlled septic condition should not
      preclude salvage surgery. Although pouch failure occurs more frequently than
      after primary ileal pouch-anal anastomosis, patient satisfaction and quality of
      life are high.

PMID- 14719145
TI  - Randomized, clinical trial of bowel confinement vs. laxative use after primary
      repair of a third-degree obstetric anal sphincter tear.
AB  - PURPOSE: Third-degree tears are generally managed by primary anal sphincter
      repair. Postoperatively, some physicians recommend laxative use, whereas others
      favor bowel confinement after anorectal reconstructive surgery. This randomized
      trial was designed to compare a laxative regimen with a constipating regimen in
      early postoperative management after primary obstetric anal sphincter repair.
      METHODS: A total of 105 females were randomized after primary repair of a third
      degree tear to receive lactulose (laxative group) or codeine phosphate
      (constipated group) for three days postoperatively. Patients were reviewed at
      three days and at three months postpartum. Recorded outcome measures were
      symptomatic and functional outcome and early postoperative morbidity. RESULTS:
      Forty-nine patients were randomly assigned to the constipated group and 56
      patients to the laxative group. The first postoperative bowel motion occurred at
      a median of four (mean, 4.5 (range, 1-9)) days in the constipated group and at
      two (mean, 2.5 (range, 1-7)) days in the laxative group (P<0.001). Patients in
      the constipated group had a significantly more painful first evacuation compared
      with the laxative group (P<0.001). The mean duration of hospital stay was 3.7
      (range, 2-6) days in the constipated group and 3.05 days in the laxative group
      (range, 2-5; P=0.001). Nine patients in the constipated group complained of
      troublesome postoperative constipation compared with three in the laxative group
      (P=0.033). Continence scores, anal manometry, and endoanal ultrasound findings
      were similar in the two groups at three months postpartum. CONCLUSIONS: Patients
      in the laxative group had a significantly earlier and less painful bowel motion
      and earlier postnatal discharge. There was no difference in the symptomatic or
      functional outcome of repair between the two regimens.

PMID- 14719146
TI  - Primary sphincter repair: are the results of the operation good enough?
AB  - PURPOSE: This study was designed to evaluate the clinical outcome of primary anal
      sphincter repair caused by obstetric tears and to analyze possible risk factors
      associated with sphincter rupture during vaginal delivery. METHODS: A total of 52
      females with a third-degree or fourth-degree perineal laceration during vaginal
      delivery were examined. The symptoms of anal incontinence were obtained by a
      standard questionnaire. In addition to a clinical examination, endoanal
      ultrasound, anal manometry, and pudendal nerve terminal motor latency
      examinations were performed. A control group consisted of 51 primiparous females
      with no clinically detectable perineal laceration after vaginal delivery.
      RESULTS: After primary sphincter repair, 31 females (61 percent) had symptoms of
      anal incontinence. Fecal incontinence occurred in 10 females (20 percent).
      According to Hardcastle and Parks' and Jorge and Wexner's classifications, the
      study group had more severe symptoms of anal incontinence than the control group
      (P<0.001 in both classification groups). In endoanal ultrasound examination, a
      persistent defect of the external anal sphincter was found in 39 females (75
      percent) in the rupture group compared with 10 females (20 percent) in the
      control group (P<0.001). Anal sphincter pressures were significantly lower in the
      rupture group than in the control group. An abnormal presentation was the only
      risk factor for anal sphincter rupture during vaginal delivery. CONCLUSIONS:
      After primary sphincter repair, persistent external anal sphincter defect and
      symptoms of anal incontinence are common in females who have had a primary
      sphincter repair after vaginal delivery. The means of improving the results of
      primary repair should be studied further.

PMID- 14719147
TI  - Anal sphincter injury after forceps delivery: myth or reality? A prospective
      ultrasound study of 93 females.
AB  - PURPOSE: This study was designed to estimate the prevalence of anal sphincter
      injury after forceps delivery in a large population of females managed by trained
      obstetricians in a French hospital and to identify factors predictive for anal
      sphincter injury. METHODS: We performed a prospective study of healthy females
      older than 18 years with no history of anal incontinence, anorectal
      abnormalities, or anorectal surgery after their first vaginal delivery. All
      females were interviewed using a standardized questionnaire concerning intestinal
      transit and continence status. Physical examination and endoanal ultrasonography
      were performed after delivery. RESULTS: Between November 1999 and November 2000,
      93 females were included in the study after their first forceps delivery. Eleven
      patients (11.8 percent) had a partial defect involving the external sphincter,
      visible on ultrasonography. One patient (1.1 percent) had a partial defect of
      external sphincter with complete defect of internal sphincter (sequelae of
      primary repair of a third-degree perineal tear). Seventeen patients (18.2
      percent) had flatus incontinence, and four patients (4.3 percent) had liquid
      stool incontinence. A high daily number of stools was significantly associated
      with sphincter defect visible on ultrasonography (P=0.02). The development of
      anal incontinence was not related to sphincter defect on ultrasonography. There
      was a strong association between perineal tear and sphincter defect visible on
      ultrasonography (odds ratio, 4.5 (range, 1.2-16.7)). CONCLUSIONS: Anal sphincter
      injury after forceps delivery was identified in <13 percent of our large
      population of healthy females. Our study does not confirm previous observations
      that anal sphincter injury is common after forceps delivery; previously published
      studies may have overestimated the prevalence of this condition. The only factor
      with significant predictive value for anal sphincter injury was perineal tear.
      Anal endosonography should be recommended after obstetric perineal tear.

PMID- 14719148
TI  - Incontinence after lateral internal sphincterotomy: a prospective study and
      quality of life assessment.
AB  - PURPOSE: Lateral internal sphincterotomy is an effective treatment for chronic
      anal fissures; however, the risk of "incontinence" has generated interest in
      pharmacologic approaches that are far less effective and may be poorly tolerated.
      This study was designed to objectively define the risk of incontinence with
      sphincterotomy using the Fecal Incontinence Severity Index and assess the
      implications for quality of life using the Fecal Incontinence Quality of Life
      Scale. METHODS: A prospective study was undertaken on all patients undergoing
      lateral internal sphincterotomy for a chronic anal fissure by a single surgeon at
      a university teaching hospital from January 1, 2000 to September 30, 2002. All
      patients had failed at least six weeks of nonoperative management. Patient
      demographics and use of nitroglycerin were noted. The Fecal Incontinence Severity
      Index was measured preoperatively and at a six-week postoperative visit when
      fissure healing and postoperative complications were assessed. The Fecal
      Incontinence Quality of Life Scale was administered to patients with an
      incontinence score>0. RESULTS: Thirty-five patients (15 males) underwent
      sphincterotomy during the study period. Thirty-one of 35 had failed nitrates: 10
      because of unacceptable side effects, and 21 because of lack of efficacy. Thirty
      two patients returned for their six-week postoperative visits, and two completed
      their questionnaires by telephone. One patient was lost to follow-up. Mean age
      was 41.2 (range, 21-67) years. Thirty of 32 (94 percent) evaluable fissures had
      healed by six weeks, one healed by three months, and the other required V-Y
      anoplasty. There were two minor complications. Three patients had postoperative
      deterioration in their continence score. Quality of life deteriorated in only one
      patient. CONCLUSIONS: Lateral internal sphincterotomy is a safe and effective
      treatment for chronic anal fissures that only occasionally impairs continence and
      rarely diminishes quality of life.

PMID- 14719149
TI  - Palliation for advanced malignant colorectal obstruction by self-expanding
      metallic stents: prospective evaluation of outcomes.
AB  - PURPOSE: This study was designed to evaluate the outcomes of self-expanding
      metallic stents as a palliative treatment for malignant obstruction of the colon
      and rectum. METHODS: The insertion of self-expanding metallic stents was
      attempted for palliation in 52 patients (33 males; mean age, 66.5 +/- 16.4 years)
      with colorectal obstruction caused by advanced malignancies. The stents were
      inserted under endoscopic and fluoroscopic guidance. The data on the success of
      the procedure, the complications, and the outcomes of the patients were collected
      prospectively. RESULTS: Thirty patients had locally advanced or disseminated
      primary colorectal cancers, and 22 had recurrent cancer of colorectal or other
      primaries. Successful insertion of the stent was achieved in 50 patients. The
      median survival of the patients was 88 (range, 3-450) days. Complications
      occurred in 13 patients (25 percent). These included perforation of the colon
      (n=1), migration or dislodgement of the stents (n=8), severe tenesmus (n=1),
      colovesical fistula (n=1), and tumor ingrowth (n=2). Insertion of a second stent
      was required in eight patients. Subsequent operations were performed in nine
      patients, and stoma creation was required in seven patients. CONCLUSIONS: Self
      expanding metallic stents are highly effective in relieving malignant colorectal
      obstruction. The complication rate is acceptable and palliation can be achieved
      in the majority of the patients without a stoma.

PMID- 14719150
TI  - Local invasion of the bladder with colorectal cancers: surgical management and
      patterns of local recurrence.
AB  - PURPOSE: Colorectal cancers may be adherent to the urinary bladder. To achieve
      oncologic clearance of the cancer, en bloc bladder resection should be performed.
      This study describes the multicenter experiences of en bloc bladder resection for
      colorectal cancer in the major New Zealand public hospitals. METHODS: A
      retrospective database of patients undergoing surgery for colorectal cancer
      adherent to the bladder between 1984 and 1999 was constructed. Data was analyzed
      for age, gender, disease stage, and outcome (local recurrence and survival).
      RESULTS: Fifty-three patients were identified: International Union Against Cancer
      and American Joint Committee on Cancer Stage 1=0; Stage 2=23; Stage 3=22; Stage
      4=6; unknown=2. Forty-five had en bloc partial cystectomy performed, four en bloc
      total cystectomy, and four had the adhesions disrupted and no bladder resection.
      The most common site of the primary colorectal cancer is sigmoid colon, with
      local invasion into the dome of the bladder. All patients who did not have en
      bloc resection developed local recurrence and died from their disease. Mean
      follow-up was 62 months. The extent of bladder resection did not seem important
      in determining local recurrence. CONCLUSIONS: En bloc resection of the urinary
      bladder should be performed if the patient is to be offered an optimal oncologic
      resection for adherent colorectal cancer. The decision to perform total rather
      than partial cystectomy should be based on the anatomic location of the tumor.
      Because the sigmoid is usually the primary site, most patients will not have
      received preoperative radiation. Therefore, postoperative radiotherapy may reduce
      local recurrence in these patients.

PMID- 14719151
TI  - Oncological outcomes after total mesorectal excision for cure for cancer of the
      lower rectum: anterior vs. abdominoperineal resection.
AB  - PURPOSE: This study was designed to examine the outcome of cancer of the lower
      rectum, particularly the rates of local recurrence and survival for tumors
      located in this area that have been treated by anterior or abdominoperineal
      resections. METHODS: A prospective, observational, national, cohort study which
      is part of the Norwegian Rectal Cancer Project. The present cohort includes all
      patients undergoing total mesorectal excision in 47 hospitals during the period
      November 1993 to December 1999. A total of 2,136 patients with rectal cancer
      within 12 cm of the anal verge were analyzed; there were 1,315 (62 percent)
      anterior resections and 821 (38 percent) abdominoperineal resections. The lower
      edge of the tumor was located 0 to 5 cm from the anal verge in 791 patients, 6 to
      8 cm in 558 patients, and 9 to 12 cm in 787 patients. According to the TNM
      classification, there were 33 percent Stage I, 35 percent Stage II, and 32
      percent Stage III. RESULTS: Univariate analyses: The five-year local recurrence
      rate was 15 percent in the lower level, 13 percent in the intermediate level, and
      9 percent in the upper level (P=0.014). It was 10 percent local recurrence after
      anterior resection and 15 percent after abdominoperineal resection (P=0.008). The
      five-year survival rate was 59 percent in the lower level, 62 percent in the
      intermediate level, and 69 percent in the upper level (P<0.001), respectively,
      and it was 68 percent in the anterior-resection group and 55 percent in the
      abdominoperineal-resection group (P<0.001). Multivariate analyses: The level of
      the tumor influenced the risk of local recurrence (hazard ratio, 1.8; 95 percent
      confidence interval, 1.1-2.3), but the operative procedure, anterior resection
      vs. abdominoperineal resection, did not (hazard ratio, 1.2; 95 percent confidence
      interval, 0.7-1.8). On the contrary, operative procedure influenced survival
      (hazard ratio, 1.3; 95 percent confidence interval, 1-1.6), but tumor level did
      not (hazard ratio, 1.1; 95 percent confidence interval, 0.9-1.5). In addition to
      patient and tumor characteristics (T4 tumors), intraoperative bowel perforation
      and tumor involvement of the circumferential margin were identified as
      significant prognostic factors, which were more common in the lower rectum,
      explaining the inferior prognosis for tumors in this region. CONCLUSIONS: T4
      tumors, R1 resections, and/or intraoperative perforation of the tumor or bowel
      wall are main features of low rectal cancers, causing inferior oncologic outcomes
      for tumors in this area. If surgery is optimized, preventing intraoperative
      perforation and involvement of the circumferential resection margin, the
      prognosis for cancers of the lower rectum seems not to be inherently different
      from that for tumors at higher levels. In that case, the level of the tumor or
      the type of resection will not be indicators for selecting patients for
      radiotherapy.

PMID- 14719152
TI  - Clinical impact of endoscopic ultrasound and endoscopic ultrasound-guided fine
      needle aspiration in the management of rectal carcinoma.
AB  - PURPOSE: There is scant data about the clinical impact of endoscopic ultrasound
      guided fine-needle aspiration in rectal carcinoma. This study was designed to
      determine the impact of endoscopic ultrasound-guided fine-needle aspiration on
      the staging and management of rectal carcinoma and to compare the staging
      accuracy of computed tomography scan, endoscopic ultrasound, and endoscopic
      ultrasound-guided fine-needle aspiration. METHODS: The records of 60 consecutive
      patients diagnosed with rectal carcinoma referred for endoscopic ultrasound
      staging were reviewed. Computed tomography scans, endoscopic ultrasound imaging,
      endoscopic ultrasound-guided fine-needle aspiration staging, surgical pathology,
      and subsequent treatment were compared. RESULTS: Of 48 patients who underwent
      computed tomography scan imaging, the additional information provided by
      endoscopic ultrasound changed management in 38 percent of patients. Sixteen
      patients identified as having nonjuxtatumoral lymph nodes underwent fine-needle
      aspiration and the additional information obtained changed therapy in three (19
      percent) of these patients. All five cases of recurrent rectal carcinoma were
      correctly diagnosed by fine-needle aspiration. Tumor staging accuracy was 45
      percent (computed tomography) and 89 percent (endoscopic ultrasound; P<0.0001);
      nodal staging accuracy was 68 percent (computed tomography), 85 percent
      (endoscopic ultrasound), and 92 percent (endoscopic ultrasound-guided fine-needle
      aspiration; P=not significant). CONCLUSIONS: Endoscopic ultrasound imaging was
      better than computed tomography scanning at overall tumor staging, whereas
      endoscopic ultrasound-guided fine-needle aspiration demonstrated a trend toward
      more accurate nodal staging. Preoperative staging with endoscopic ultrasound
      resulted in a change of management in 38 percent of patients. The addition of
      fine-needle aspiration changed the management in 19 percent of those who
      underwent nonjuxtatumoral lymph node sampling. Endoscopic ultrasound-guided fine
      needle aspiration accurately diagnosed 100 percent of those with recurrent rectal
      carcinoma. Clearly, endoscopic ultrasound and endoscopic ultrasound-guided fine
      needle aspiration are important for the staging and management of rectal
      carcinoma and for detecting disease recurrence.

PMID- 14719153
TI  - Colorectal cancer staging: reappraisal of N/PN classification.
AB  - PURPOSE: Current American Joint Committee on Cancer and the Union Internationale
      Contre le Cancer TNM classification disregards location of positive nodes,
      discontinuing N3 category, which constitutes a major modification to 1987
      version. This study was designed to assess the impact of the recategorization of
      former N3 cases and the reliability of the current N1-N2 subcategorization of
      Stage III patients. METHODS: Prospectively collected data from 1,391 patients
      (55.8 percent males; median age, 64 (range, 21-97) years), operated on with
      curative intent between 1980 and 1999, were analyzed. The median follow-up was 60
      (interquartile range, 27-97) months with 129 cases lost to follow-up. RESULTS: Of
      positive node cases, 25.3 percent were former N3. Among them, 30.5 percent
      migrated to the N1 group and 69.5 percent to the N2 group. The proportions of
      former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent,
      respectively (P<0.001). Node-positive patients had an actuarial five-year
      survival rate of 56.7 percent (95 percent confidence interval, 53-59), with a
      significant difference between N1/N2 categories (63.6 vs. 44.1 percent,
      respectively; P<0.001). Although apical node involvement and more than three
      positive nodes were associated with poorer outcomes in univariate analysis, only
      the number of positive nodes had independent association (hazard ratio, 1.6
      (range, 1.2-2.2); P<0.001). Integration of former N3 cases did not modify
      outcomes. CONCLUSIONS: The recategorization of former N3 involved a high
      proportion of positive node cases. Current N1/N2 categories clearly defined
      different outcomes and were not modified by the integration of former N3.

PMID- 14719154
TI  - Overexpression of cyclooxygenase-2 correlates with chromosomal gain at the
      cyclooxygenase-2 locus and decreased patient survival in advanced colorectal
      carcinomas.
AB  - PURPOSE: Overexpression of cyclooxygenase-2 is observed in a variety of
      malignancies including colorectal cancer. However, to date, cyclooxygenase-2
      expression by advanced human colorectal cancers and their metastases has been
      poorly characterized. This study was designed to evaluate the rate of
      cyclooxygenase-2 overexpression in our tumor collection and to clarify its
      correlation with the chromosomal status at the cyclooxygenase-2 locus in
      colorectal cancer. METHODS: Seventy-four specimens were analyzed
      immunohistochemically using a monoclonal cyclooxygenase-2 antibody. The staining
      was scored semiquantitatively as: -, negative; +, weak; ++, moderate; and +++,
      strong positive. Of these, 45 specimens were analyzed using comparative genomic
      hybridization and immunohistochemistry. We correlated the cyclooxygenase-2
      overexpression with the chromosomal gain of 1q25.2-q25.3 and patients survival
      and compared primary colorectal cancers and their paired metastases at the DNA
      and protein level. RESULTS: Overexpression was observed in 58 percent of the
      cases (score > or = ++). Chromosomal gains at the cyclooxygenase-2 locus were
      clearly correlated with overexpression of the gene (P=0.009). Furthermore, the
      comparison of paired tumor samples showed additional overrepresentation in the
      metastases at the cyclooxygenase-2 locus, which could be confirmed by
      immunohistochemistry. Kaplan-Meier analysis showed that overexpression of
      cyclooxygenase-2 was significantly associated with poor survival and thus could
      serve as a prognostic marker. CONCLUSIONS: We conclude that cyclooxygenase-2 is
      related with tumor progression and metastasis in colorectal cancer, which can be
      observed on protein level, and reflects chromosomal gain at the locus at 1q25.2
      q25.3.

PMID- 14719155
TI  - Incidence and survival of mucinous adenocarcinoma of the colorectum: a population
      based study from an Asian country.
AB  - PURPOSE: Previous studies have shown conflicting results on the prognosis of
      mucinous adenocarcinoma of the colorectum. This could be because of heavy bias on
      patient selection. Furthermore, little data are available from Asian populations.
      This study was designed to examine incident and prognostic characteristics of
      mucinous adenocarcinoma of the colorectum based on data obtained from a
      population-based, Asian, cancer registry. METHODS: A total of 627 of 15,762 were
      mucinous adenocarcinoma cases from invasive colorectal cancer patients registered
      in the Singapore Registry from 1968 to 1997. Age-standardized incidence rate was
      used to describe the incident pattern of mucinous adenocarcinoma of colon and
      rectum during a period of time. Survival of patients with mucinous adenocarcinoma
      or ordinary adenocarcinoma was compared using relative survival and proportional
      hazards model. RESULTS: Age-standardized incidence rate of mucinous
      adenocarcinoma of the colon and rectum were almost unchanged in males, rising
      slightly in females during the study periods from 1968 to 1972 to 1993 to 1997.
      The proportion of mucinous adenocarcinoma cases was similar among genders and
      calendar-year periods but was higher in younger age groups, Malays and Indians,
      in advanced stages of the disease, and proximal colon. Five-year relative
      survival rate of patients with mucinous adenocarcinoma were similar in the colon
      but were lower in the rectum. CONCLUSIONS: Colorectal mucinous adenocarcinoma as
      a different etiologic entity from other histologic types of colorectal cancer was
      suggested. Possibly greater aggressiveness of mucinous adenocarcinoma occurring
      in the rectum requires confirmation but suggests that mucin is important in the
      pathogenesis of mucinous adenocarcinoma.

PMID- 14719156
TI  - Outcome of colectomy for slow-transit constipation in relation to presence of
      small-bowel dysmotility.
AB  - PURPOSE: A significant proportion of patients with slow-transit constipation have
      abnormal small-bowel motility. It is unclear whether abnormal small-bowel
      motility indicates worse results after surgery for slow-transit constipation. We
      studied the results of colectomy with ileorectal anastomosis in patients with
      normal and abnormal antroduodenal manometry findings. METHODS: Seventeen,
      consecutive patients who had been referred for intractable constipation and who
      were found to suffer from slow-transit constipation underwent subtotal colectomy.
      All patients underwent a set of diagnostic investigations, including whole gut
      transit time, anorectal manometry, antroduodenal manometry, electromyography of
      the anal sphincter, balloon expulsion test, and defecography. Patients were
      followed up after five years. RESULTS: Patients' median age at the time of the
      operation was 46 (range, 23-70) years, and the median duration of constipation
      was 31 (range, 11-65) years. One patient died 21 days after the operation. Three
      patients developed intestinal pseudo-obstruction after the operation, and two of
      these died during the follow-up period. Fourteen patients were available for
      follow-up after a median of five (range, 4-7) years. Bowel frequency was
      significantly increased from a median of 0 (range, 0-2) times per week to a
      median of 30 (range, 10-102) times per week after surgery (P<0.001). The
      incidence of abdominal pain decreased from 94 to 43 percent. Seven of 13 patients
      (54 percent) continued to have bloating. At long-term follow-up, 12 of 14
      patients (86 percent) reported that they had an overall improvement after
      surgery, despite continuing pain and bloating in a significant proportion of
      them. The outcome of surgery was good or excellent in seven of seven patients
      with normal findings on antroduodenal manometry, but only five of nine patients
      with abnormal manometry findings attained a good result after surgery. We found a
      trend (P=0.09) toward better long-term results after surgery for slow-transit
      constipation in patients with a normal antroduodenal manometry before the
      operation.

PMID- 14719157
TI  - Ultrasound study of anal fistulas with hydrogen peroxide enhancement.
AB  - PURPOSE: This study was designed to evaluate the effectiveness of hydrogen
      peroxide-enhanced, endoanal ultrasound in the assessment of fistula-in-ano and
      compare ultrasonographic results with the surgical outcome. METHODS: A total of
      80 patients with anal fistula were studied prospectively by physical examination
      and endoanal ultrasound enhanced with hydrogen peroxide. We used standardized
      ultrasonography and operation notes. The results of these studies were compared
      with the surgical findings. The ultrasonographic study of the anal canal
      describes the fistula's characteristics, which provides an ultrasonographic
      classification of the fistula. All endoanal ultrasounds were performed by
      colorectal surgeons. RESULTS: In 94 percent of the cases, the internal opening
      was identified. In only one case were we unable to obtain sufficient information
      about the tract and the fistula's level. The endoanal ultrasound was able to
      correctly identify whether the tract was linear or curvilinear in 95 percent of
      the cases. The ultrasound level coincided with surgical findings in 85 percent of
      patients, and chronic fistula cavities were confirmed by surgery in 75 percent of
      patients. CONCLUSIONS: The use of endoanal ultrasound, with hydrogen peroxide
      enhancement, by a colorectal surgeon with adequate experience in endoanal
      ultrasound provides excellent results in the presurgical examination of fistula
      in-ano.

PMID- 14719158
TI  - Sister Mary Joseph's nodule as a first sign of cancer of the cecum: report of a
      case.

PMID- 14719159
TI  - Antiangiogenic treatment of mesenteric desmoid tumors with toremifene and
      interferon alfa-2b: report of two cases.
AB  - PURPOSE: Desmoid tumors are uncommon, benign, fibrous lesions occurring
      sporadically and in association with familial adenomatous polyposis. Typical
      clinical features include a locally aggressive behavior, an unpredictable course,
      and a high propensity for recurrence after surgical resection. There are no
      standard medical or surgical approaches, and no markers for monitoring medical
      therapy of desmoid tumors. METHODS: We report two cases of mesenteric desmoid
      tumors treated with interferon alfa-2b and toremifene, a novel regimen devised to
      block angiogenesis. Pre- and posttreatment desmoid tumor tissues were obtained in
      one patient during a repeat resection for recurrent stenosing Crohn's disease and
      examined for mean vessel count and cellular proliferation levels by
      immunostaining for the endothelial surface antigen CD31 and the proliferation
      associated nuclear antigen, Ki-67, respectively. We assessed plasma D-dimers, a
      potential marker of angiogenic activity, and followed this throughout the course
      of antiangiogenic therapy in our two patients. RESULTS: Examination of
      posttreatment tissue revealed a significant decrease in microvessel density
      (P<0.02) and Ki-67-positive nuclei (P<0.0001) compared with pretreatment tissue.
      Both patients demonstrated a prompt and sustained drop in previously elevated
      plasma D-dimer levels, which correlated clinically with lesion regression and
      sustained remission. CONCLUSIONS: Treatment with toremifene and interferon alfa
      2b was successful and well tolerated in our two patients. Our data suggest a
      combined antiangiogenic and antiproliferative mechanism of action. Furthermore,
      normalization of previously elevated plasma D-dimers may emerge as a strategy to
      monitor treatment efficacy in mesenteric desmoid tumors.

PMID- 14719160
TI  - Large villous adenomas arising in ileal pouches in familial adenomatous
      polyposis: report of two cases.
AB  - A restorative proctocolectomy or ileal pouch procedure is one of the main
      surgical options for patients with familial adenomatous polyposis. The main
      premise underlying the recommendation of a pouch procedure rather than an
      ileorectal anastomosis is that it minimizes the risk of rectal cancer. Several
      studies have evaluated the risk of developing pouch adenomas. There also have
      been reports of pouch cancers, although the long-term risk of malignancy cannot
      yet be quantified. Most pouch polyps reported have been small tubular adenomas
      with mild dysplasia. A 19-year-old female with familial adenomatous polyposis had
      a colectomy and ileorectal anastomosis. Progressive rectal polyposis led to a
      restorative proctocolectomy at aged 38 years. Four years later, a large, 3-cm x 2
      cm, villous adenoma was identified in the mid pouch, which was resected
      endoscopically. A 32-year-old male with familial adenomatous polyposis had a
      restorative proctocolectomy. Ten years after surgery, pouch endoscopy revealed
      several large, villous adenomas arising from the pouch mucosa. These advanced
      polyps may present a significant risk for cancer development and require close
      endoscopic surveillance. These findings strengthen the recommendation for careful
      regular endoscopic surveillance of familial adenomatous polyposis pouches and the
      evaluation of management and treatment strategies for pouch adenomas.

PMID- 14719161
TI  - High frequency and large number of polymorphic microsatellites in cultured
      shrimp, Penaeus (Litopenaeus) vannamei [Crustacea:Decapoda].
AB  - A total of 1479 recombinant clones were obtained from a Sau3A-digested genomic
      library of Penaeus (Litopenaeus) vannamei and used for probe hybridization. Of
      the 251 clones that tested positive to one or more of the probes and were
      sequenced, 173 (69%) contained 573 simple sequence repeats, or microsatellites,
      with 3 or more repeats. The frequency of microsatellites with 3, 5, and 10 or
      more repeats was 1 in 0.94 kb, 1 in 2.78 kb, and 1 in 5.94 kb, respectively. To
      increase the number of polymorphic markers for mapping, 136 primer sets that
      flanked microsatellites containing single or multiple motifs with 3 or more
      repeats were designed and tested. Of the 136 primers, 93 (68.0%) were polymorphic
      in cultured shrimp, with polymorphism information content (PIC) values ranging
      from 0.195 to 0.873, and observed heterozygosities ranging from 10% to 100%.
      These markers are being used along with other markers to construct a linkage map
      for P. vannamei.

PMID- 14719162
TI  - Seafood allergy and allergens: a review.
AB  - Seafoods are composed of diverse sea organisms and humans are allergic to many of
      them. Tropomyosin is a major allergen in many shellfish, especially crustacea and
      mollusks. Interestingly, tropomyosin has also been identified as an important
      allergen in other invertebrates including dust mites and cockroaches, and it has
      been proposed by some to be an invertebrate pan allergen. Different regions of
      shrimp tropomyosin bind IgE; 5 major IgE-binding regions have been identified in
      shrimp tropomyosin containing 8 epitopes. Mutations of these shrimp allergenic
      epitopes can reduce seafood allergenicity; methods utilizing such mutations will
      provide safer vaccines for more effective treatment of seafood-allergic patients,
      and in the future less-allergenic seafood products for consumption.

PMID- 14719163
TI  - Filamentous marine fungi as producers of O-glycosylhydrolases: beta-1,3-glucanase
      from Chaetomium indicum.
AB  - Ninety fungal strains (42 species) isolated from marine habitats were studied for
      their ability to produce extracellular enzymes. Cultural filtrates of these
      strains were shown to contain a series of glycosidases (beta-glucosidases, N
      acetyl-beta-glucosaminidases, beta-galactosidases alpha-mannosidases) and
      glucanases (1,3-beta-glucanases, amylases) which varied with habitat. The level
      of activity depended on the species of fungi. Several promising strains capable
      of producing both individual enzymes and a set of enzymes for splitting
      carbohydrate-containing compound have been isolated. Optimal conditions for
      growth of Chaetomium indicum and for biosynthesis of beta-1,3-glucanase were
      determined. beta-1,3-Glucanase was isolated using ion-exchange chromatography,
      ultrafiltration, and gel filtration. The presence of 2 enzyme forms was shown;
      both forms were exo-beta-1,3-glucanases.

PMID- 14719164
TI  - Structure of amylase genes in populations of Pacific Cupped oyster ( Crassostrea
      gigas): tissue expression and allelic polymorphism.
AB  - Using the previously determined complementary DNA Sequence of Crassostrea gigas
      amylase (Y08370), we designed several oligonucleotide primers and used them with
      polymerase chain reaction (PCR) technology to characterize oyster amylase gene
      sequences. Two genes encoding 2 different amylases were characterized and
      sequenced. The 2 genes are similarly organized with 8 exons and 7 introns. Intron
      insertions are found at the same location in the 2 genes. Sizes and nucleotide
      sequences are different for the different introns inside each gene and different
      for the corresponding introns in the 2 genes. Comparing the 2 genes, around 10%
      of the nucleotides are different along the exons, and comparing the 2 deduced
      protein sequences, a mean value of 10.4% of amino acids are changed. Genes A and
      B encode mature proteins of, respectively, 500 and 499 amino acids, which present
      94% similarity. A microsatellite (TC(37)) that constitutes the largest part of
      intron 4 of gene A has been used as a polymorphic marker. A method consisting of
      a PCR step followed by EcoRI digestion of the obtained fragments was used to
      observe polymorphism in these 2 genes. Six and 4 alleles for genes A and B,
      respectively, have been sequenced, leading to a maximum of 2.9% base change. The
      2 genes are ubiquitously expressed in the different digestive tissues with
      quantitative differences. Gene A is strongly expressed in the digestive gland and
      at a lower level in stomach, while gene B is preferentially expressed in the
      labial palps. The microsatellite repeat was used in the analysis of 4 populations
      of Crassostrea gigas from the French Atlantic coast. A high level of polymorphism
      observed with 30 different alleles of gene A inside the populations should allow
      their characterization using the mean value of the microsatellite allelic
      distribution. These populations showed a low level of differentiation ( F(st)
      between 0 and 0.011); however, the population of Bonne Anse appeared to be
      distinguished from the other populations.

PMID- 14719165
TI  - Expression of biologically active crustacean hyperglycemic hormone (CHH) of
      Penaeus monodon in Pichia pastoris.
AB  - Crustacean hyperglycemic hormone (CHH), molt-inhibiting hormone (MIH), and gonad
      inhibiting hormone (GIH) are members of a major peptide family produced from the
      X-organ sinus gland complex in the eyestalk of crustaceans. This peptide family
      plays important roles in controlling several physiologic processes such as
      regulation of growth and reproduction. In this study the complementary DNA
      encoding a peptide related to the CHH/MIH/GIH family (so-called Pem-CMG) of the
      black tiger prawn Penaeus monodon was successfully expressed in the yeast Pichia
      pastoris under the control of the AOX1 promoter. The recombinant Pem-CMG was
      secreted into the culture medium using the alpha-factor signal sequence; of
      Saccharomyces cerevisiae without the Glu-Ala-Glu-Ala spacer peptide. The amino
      terminus of the recombinant Pem-CMG was correctly processed as evidenced by amino
      terminal peptide sequencing. The recombinant Pem-CMG was purified by reverse
      phase high-performance liquid chromotography and used in a biological assay for
      CHH activity. The final yield of the recombinant Pem-CMG after purification was
      260 micro g/L of the culture medium. Both crude and purified recombinant Pem-CMG
      produced from P. pastoris showed the ability to elevate the glucose level in the
      hemolymph of eyestalk-ablated P. monodon, which demonstrates that Pem-CMG peptide
      functions as hyperglycemic hormone in P. monodon.

PMID- 14719166
TI  - Purification of sulfated fucoglucuronomannan lyase from bacterial strain of
      Fucobacter marina and study of appropriate conditions for its enzyme digestion.
AB  - A marine bacterial strain, Fucobacter marina, produced extracellular sulfated
      fucoglucuronomannan (SFGM) lyase when cultivated in the presence of crude SFGM
      obtained from fucoidan of Kjellmaniella crassifolia (brown algae) by cetyl
      pyridinium chloride fractionation. For the SFGM lyase assay, SFGM fraction
      separated from K. crassifolia fucoidan by anion exchange column chromatography
      was used as the substrate. The extracellular SFGM lyase was purified to
      homogeneity on an electrophoresis gel with 4240-fold purity at 13.8% yield. The
      enzyme proved to be a monomer, since gel filtration and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gave the same relative molecular mass of
      67,000. The enzyme specifically digested SFGM but did not digest any other uronic
      acid-containing polysaccharides tested. The optimum conditions for the enzyme
      reaction were around pH 7.5, 43 degrees C, and 0.4 M NaCl concentration. The
      enzyme was strongly inhibited by CuCl(2) and ZnCl(2), and also by some sulfhydryl
      reagents.

PMID- 14719167
TI  - Monoclonal antibody specific to urochordate Botryllus schlosseri pyloric gland.
AB  - We describe here the development of a new hybridoma cell line, CF12F6, that
      produces a specific antibody to Botryllus schlosseri (a colonial tunicate). The
      monoclonal antibody was isotyped as IgG1 (by enzyme-linked immunosorbent assay),
      and the cellular localization of the antigenic epitope that reacts specifically
      with CF12F6 was confined to the cells of the pyloric gland of the zooid (by
      immunohistochemistry). The pyloric gland participates in osmoregulation,
      digestion, glycogen storage, and various other secretion functions that will be
      studied further by the use of monoclonal antibody CF12F6, the first in botryllid
      ascidians that recognizes cells of a whole, single organ.

PMID- 14719168
TI  - Platelet aggregation inhibitors from Philippine marine invertebrate samples
      screened in a new microplate assay.
AB  - A new microplate assay for Ca(2+)-induced platelet aggregation as detected by
      Giemsa dye was used to screen marine invertebrate samples from the Philippines
      for inhibitors of human platelet aggregation. Out of 261 crude methanol extracts
      of marine sponges and tunicates, 25 inhibited aggregation at 2 mg/ml. Inhibition
      of agonist-induced aggregation in an aggregometer was used to confirm results of
      the microplate assay and to determine the specific mode of inhibition of 2
      samples. The marine sponge Xestospongia sp. yielded a xestospongin/araguspongine
      type molecule that inhibited collagen-induced aggregation by 87% at 2 micro g/ml,
      and epinephrine-induced aggregation by 78% at 20 micro g/ml, while the marine
      sponge Aplysina sp. yielded 5,6-dibromotryptamine, which inhibited epinephrine
      induced aggregation by 51% at 20 micro g/ml. In this study we have found that the
      microplate assay is a simple, inexpensive, yet useful preliminary tool to
      qualitatively screen a large number of marine samples for antiplatelet
      aggregation activity.

PMID- 14719169
TI  - Molecular phylogenetic relationships between prostanoid-containing Okinawan soft
      coral ( Clavularia viridis) and nonprostanoid-containing Clavularia species based
      on ribosomal ITS sequence.
AB  - To study phylogenetic relationships among Okinawan soft corals of the genus
      Clavularia, the ribosomal internal transcribed spacer sequences of host corals
      and the 18S rDNA sequences of symbiotic algae were analyzed. The molecular
      phylogenetic trees of hosts showed that a prostanoid-containing species,
      Clavularia viridis, is deeply diverged from other species of Clavularia which do
      not biosynthesize the prostanoids as the main secondary metabolites. Comparison
      of their trees suggested poor phylogenetic concordance between hosts and
      symbionts.

PMID- 14719171
TI  - Thrombosis in pediatric cardiac patients.
AB  - Cardiac disease and thrombosis are intimately related in adults, but primary
      myocardial infarction in children is rare. Homozygous familial hyperlipidemia
      occurs in approximately 1 million children, and causes severe coronary artery
      disease during childhood. Kawasaki's disease is an acquired inflammatory
      disorder, which, if untreated, leads to coronary artery aneurysms and subsequent
      myocardial infarction. The current understanding of the pathophysiology and
      management of these conditions is discussed. More commonly, the relationship
      between cardiac disease in children and thrombosis is that children being treated
      for congenital structural cardiac disease develop iatrogenic thrombosis, most
      commonly precipitated by central venous access. The epidemiology of common
      treatment-induced thrombosis is described, and management guidelines presented.
      Finally, many cardiac surgical procedures increase the risk of thrombosis, and
      prophylactic antithrombotic therapy is commonly used. The current evidence for
      prophylaxis in different clinical situations is presented. Additional study is
      required in all areas to improve the outcome for children affected by cardiac
      disease and thrombosis.

PMID- 14719172
TI  - Arterial thromboembolism in the pediatric population.
AB  - The most common cause of arterial thromboembolism in the pediatric population is
      secondary to arterial catheterization. Non-catheter-related arterial
      thromboembolism is rare. The frequency of this complication has paralleled the
      advances in pediatric tertiary care that has lead to increasing numbers of
      children surviving life-threatening primary illnesses. Previously, these events
      were very rare and children were managed according to adult protocols. It is now
      known that the pathophysiology of thrombosis in children differs from that of
      adults and indeed is different for that of various age groups within the
      pediatric population, therefore requiring a unique diagnostic and therapeutic
      approach. This review highlights the available published data to support an
      evidence-based approach to the complication of arterial thromboembolism in the
      pediatric population, and underscores the urgent need for further randomized
      controlled trials.

PMID- 14719173
TI  - Arterial ischemic strokes in infants and children: an overview of current
      approaches.
AB  - Stroke in children is increasingly recognized. The incidence exceeds 8 per
      100,000 per year. Important differences in stroke in newborns and children
      compared with adults, as well as a paucity of clinical trials, create challenges
      in the diagnosis and management of pediatric arterial ischemic stroke (AIS). The
      neurological presentation of AIS can be subtle. Radiographic diagnosis of acute
      AIS is also challenging because CT scan may be normal early on. Risk factors
      include vascular, intravascular, and embolic disorders; frequently, there are
      multiple risk factors in a given child, necessitating thorough investigations.
      More than 50% have a vasculopathy including postvaricella angiopathy, dissection,
      moyamoya, or vasculitis. Intravascular mechanisms are frequently present,
      including dehydration. Hematological or prothrombotic conditions are also
      associated with AIS in children, and include sickle cell disease and
      prothrombotic disorders. The latter have been identified in from one third to one
      half of children with AIS, are usually acquired, and frequently act in concert
      with other risk factors for stroke. The most common embolic source is congenital
      heart disease, which is present in 25% of children with AIS. Outcomes include
      death in 6% and neurological deficits in two thirds of children. Given that no
      clinical trials have been completed in pediatric stroke to date, treatment is
      empiric. Initial neuroprotective strategies aim to reduce the size of the
      infarct. For older children antithrombotic agents (antiplatelet drugs and
      anticoagulants) are given to reduce the 20 to 30% risk of recurrence. There are
      coordinated research efforts currently being initiated, which over the next
      decade will result in clinical trials in this understudied condition.

PMID- 14719175
TI  - Advances in care of children with hemophilia.
AB  - Care for children with severe hemophilia has moved from pediatric hospital wards
      and rehabilitation services to the home, school, and community. Advances in
      hemophilia are due largely to the development of specialized hemophilia treatment
      centers, which created a system of comprehensive care and focused healthcare
      efforts on prevention and education. Parallel advances in coagulation resulted in
      identification of clotting factors VIII and IX, elucidation of the protein
      molecular and biochemical structures and functions, sequencing of their
      respective genes and transfer of the human genes for production of proteins by
      recombinant technology, and development of gene therapy. The tragedy of the human
      immunodeficiency virus and hepatitis C raised awareness in patients as well as
      healthcare providers of the vulnerability of blood products to viral
      contamination and spurred progress in science leading to viral inactivation of
      purified proteins. Concomitantly, physicians treating bleeding episodes in the
      clinic investigated pharmacokinetics and pharmacoeconomics of various strategies
      of clotting factor replacement. The observation that trough factor levels as low
      as 1 to 2% were adequate to prevent most bleeding episodes led to current
      prophylactic regimens that allow boys to participate fully in school and
      community activities while factor concentrate is infused at home on a regular
      schedule. Currently, children with hemophilia look forward to a normal life
      expectancy and excellent health-related quality of life. Physician and community
      partnerships through research and advocacy societies have accelerated clinical
      advancements as well as extension of treatment to developing countries. The
      future of hemophilia promises a cure with gene therapy. Given the past
      accomplishments in hemophilia, a long-term solution to replacement of the
      genetically deficient protein lies on the horizon.

PMID- 14719174
TI  - The impact of single nucleotide polymorphisms of the thrombin activatable
      fibrinolysis inhibitor (TAFI) gene on TAFI antigen levels in healthy children and
      pediatric oncology patients.
AB  - The thrombin activatable fibrinolysis inhibitor (TAFI) influences the pathways
      regulating fibrin formation and deposition. The enormous TAFI plasma level
      variability present in adults may be explained by a combination of two
      polymorphisms in the TAFI gene (+1542C>G; 505G>A). We aimed to correlate these
      two polymorphisms with plasma TAFI antigen concentrations in healthy children and
      pediatric oncology patients with and without venous thrombosis who were supplied
      with Broviac central venous catheters. Polymorphisms were detected by restriction
      fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR)
      amplification, whereas TAFI concentration was determined using a commercial
      enzyme-linked immunosorbent assay (ELISA). Samples from 57 controls and 67
      pediatric patients (11 venous thrombotic complications) were studied. TAFI levels
      in healthy children and patients were not influenced by gender or age. Compared
      with the 505GG carriers (wild type), 505AA carriers as well as heterozygous 505GA
      carriers each exhibited significantly higher TAFI antigen concentrations. In
      contrast, the lowest TAFI levels were detected in homozygous carriers of the
      +1542GG polymorphism. A combination of the genotype 505AA (homozygous carrier)
      and +1542CC (wild type) was present in 13 probands and resulted in the highest
      TAFI levels. Although in oncologic patients the risk of thrombosis was markedly
      increased by the heterozygous factor V 1691G>A mutation, the two TAFI
      polymorphisms investigated exerted no thrombogenic influence.

PMID- 14719176
TI  - Severe chronic idiopathic thrombocytopenic purpura during childhood: definition,
      management, and prognosis.
AB  - Chronic idiopathic thrombocytopenic purpura (ITP) can be categorized as mild,
      moderately severe, or severe. Severe chronic ITP during childhood is a rare
      disorder characterized by clinically significant mucocutaneous hemorrhage,
      usually in the setting of marked thrombocytopenia. It can cause substantial
      morbidity and rarely mortality. Many patients improve with time or even fully
      recover, but for those whose quality of life is negatively influenced by
      hemorrhage or side effects of conventional therapy (corticosteroids, intravenous
      immunoglobulin G, or anti-D), splenectomy is recommended. If splenectomy is
      unsuccessful or not feasible, other drug treatments are available, but few
      efficacy data exist, and the toxicity and cost of these treatments can be
      appreciable. Their use is best avoided outside of clinical trials conducted in
      specialty centers or in multi-institutional networks.

PMID- 14719177
TI  - Childhood acute immune thrombocytopenic purpura: 20 years later.
AB  - Childhood acute immune thrombocytopenic purpura (ITP) is a typically benign, self
      limiting illness usually occurring after an infectious disease. Most affected
      children have platelet counts < 20 x 10 (9)/L at presentation and are at small,
      but definite risk for an intracranial hemorrhage. This feared complication occurs
      in < 1% of all children with acute ITP. There is consensus that a bone marrow
      aspirate should be performed in children with acute ITP and atypical features
      (e.g., hepatosplenomegaly), and most physicians continue to recommend this
      investigation before corticosteroids are administered. Issues such as
      hospitalization versus observation at home, and treatment versus no treatment
      continue to be debated; there is consensus, however, that children with extreme
      thrombocytopenia (platelet counts < 10 x 10 (9)/L) and/or clinically significant
      hemorrhage merit treatment with a regimen known to rapidly increase the
      circulating platelet count. Candidate regimens include high-dose intravenous
      (IV)/oral corticosteroids (>/= 4 mg/kg/day of prednisone or an equivalent
      corticosteroid preparation), IV immunoglobulin (IG; 0.8 to 1.0 g/kg once) or IV
      anti-D (75 microg/kg once) for Rhesus-positive patients. For those rare children
      with organ- or life-threatening hemorrhage (e.g., intracranial hemorrhage)
      multimodality therapy including platelet transfusion, IV high-dose
      methylprednisone (30 mg/kg, maximum 1 g) and IVIG (1 g/kg) is indicated with
      consideration of emergency splenectomy. Future prospective trials should include
      outcome measures other than the platelet count alone (e.g., bleeding scores) and
      health-related quality-of-life assessments. Key questions that remain to be
      addressed in children with acute ITP include the need for bone marrow aspiration
      in typical cases if corticosteroid therapy is planned, the role of
      hospitalization, and most important, the unresolved issue of treatment versus no
      treatment, especially in patients with typical features and mild clinical
      bleeding symptoms.

PMID- 14719178
TI  - New anticoagulants.
AB  - The limitations of heparin and warfarin have prompted the search for new
      anticoagulants for the prevention and treatment of venous and arterial
      thromboembolism. Although many such agents are in development, only a few have
      reached phase II or higher levels of clinical testing. This article reviews
      venous and arterial thrombogenesis, discusses the regulation of coagulation,
      identifies the molecular targets for new anticoagulants currently under
      development, describes the agents in more advanced stages of clinical testing,
      and provides clinical perspective on the opportunities for new anticoagulant
      drugs.

PMID- 14719179
TI  - Anticoagulation during pregnancy.
AB  - Venous thromboembolism (VTE) occurs infrequently but is a leading cause of
      illness and death during pregnancy and the puerperium. In the general population
      the incidence of pregnancy-associated VTE is approximately 1 in 1500 deliveries.
      The risk of VTE is five times higher in a pregnant than in a nonpregnant woman.
      Postpartum the VTE risk is even higher. Women with congenital abnormalities or
      persistent presence of antiphospholipid antibodies have an increased risk of VTE
      during pregnancy and the puerperium. Women with previous VTE have an
      approximately 3.5-fold increased risk of recurrent VTE during pregnancy. Heparin
      does not cross the placenta and is therefore the anticoagulant of choice. In case
      of acute thrombosis during pregnancy, treatment is performed in the same manner
      as for nonpregnant patients. There is an ongoing debate whether pregnant women
      with previous venous thrombosis should routinely receive prophylactic
      anticoagulation. Patients who have hereditary antithrombin deficiency,
      antiphospholipid antibodies, a combined abnormality, or a history of a severe
      thrombotic event (pulmonary embolism or extended deep vein thrombosis) should be
      advised to use prophylactic heparin during pregnancy, starting during the first
      trimester. Postpartum prophylaxis should be given to all women with an increased
      risk for VTE. A large body of evidence has been presented that hypercoagulability
      may cause recurrent abortions, stillbirth, and preeclampsia. There is no doubt
      that the antiphospholipid syndrome is strongly associated with fetal loss. The
      combination of heparin and aspirin significantly decreases the fetal loss rate
      during pregnancy and thus this is the treatment of choice in this patient group.
      Several studies indicate that women with recurrent miscarriage may benefit from
      heparin administration during pregnancy, however, data from controlled trials
      have not yet been published. In women with artificial heart valves, maternal and
      fetal complications are frequent despite anticoagulation, but oral anticoagulants
      can reduce the risk for maternal complications.

PMID- 14719180
TI  - Anticardiolipin beta2-glycoprotein I antibody: is a high titer related to
      unfavorable pregnancy outcome?
AB  - We present the clinical characteristics of pregnancy histories and subsequent
      pregnancy outcomes of 13 women who tested positive for anticardiolipin beta2
      glycoprotein I antibody (aCLbeta2GPI). Six of the 13 women had a history of
      recurrent spontaneous abortion (RSA). The prevalence of aCLbeta2GPI syndrome
      among women with RSA was very low (2.1%). Other women with aCLbeta2GPI were
      identified by the presence of a biological false-positive serological test for
      syphilis, intrauterine growth restriction (IUGR), and a history of thrombosis.
      However, serum aCLbeta2GPI titers in the 13 women varied, with a wide range from
      3.6 to 1468 U/mL. Their pregnancy histories, subsequent pregnancy outcomes, and
      complications were compared according to the classification of serum aCLbeta2GPI
      titers as low, moderate, or high. The history of second trimester fetal death was
      found only in women with high serum aCLbeta2GPI titers. All women with high serum
      aCLbeta2GPI titers experienced severe maternal-fetal complications such as IUGR,
      fetal distress, systemic thromboembolism, and neonatal sequelae in subsequent
      pregnancies.

PMID- 14719181
TI  - Treatment of severe preeclampsia with antithrombin concentrate: results of a
      prospective feasibility study.
AB  - The prospective feasibility study was designed to determine whether treatment
      with antithrombin (AT) concentrates could be used for patients with severe
      preeclampsia to provide clinical efficacy without the full systemic
      antihypertensive drug. Twenty-nine severe preeclamptic patients (24 to 36 weeks
      of gestation, gestosis index [GI] >/= 6 points) were randomized to receive AT
      (1500 U/day) or not. AT was given intravenously once daily for 7 consecutive
      days. Twenty-four hours of continuous infusion of 5000 U/day of unfractionated
      heparin was given simultaneously in both groups. There were no statistical
      differences in the clinical profiles of the two groups. Maternal symptoms were
      evaluated from the difference of GI before and after treatment, and fetal
      findings were evaluated from the changes of the biophysical profile score.
      Improvement was significantly greater in the AT group for both the GI ( P =
      0.046) and the biophysical profile score ( P = 0.022). The improvement of
      coagulation parameters was also evaluated. The improvement of plasmin-plasmin
      inhibitor complex (PPIC), D-dimer levels, and platelet counts was observed in the
      AT group compared with the non-AT group. The coagulation index as a composite
      coagulation test parameter showed a significantly improvement in the AT group. No
      adverse events related to AT were observed. Given that AT plus heparin was
      significantly better than treatment with heparin alone for improvement of both GI
      and biophysical profile of infant, it is suggested that therapy with AT alone
      might be effective enough for severe preeclampsia.

PMID- 14719182
TI  - Association between a variant of the glutathione S-transferase P1 gene (GSTP1)
      and hypertension in pregnancy in Japanese: interaction with parity, age, and
      genetic factors.
AB  - Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a
      multifactorial disease. Recently, an Ile105Val variant of the glutathione S
      transferase P1 gene ( GSTP1) was shown to be associated with PE in The
      Netherlands. We therefore performed an association study of the Ile105Val variant
      comparing 131 patients with HP and 327 normal pregnant controls in Japan. We
      analyzed the data in the context of other risk factors before pregnancy. The
      frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly
      different between the HP (26%) patients and the controls (28%). However, in
      primiparous patients, the frequency was significantly different in elderly
      pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with
      the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in
      controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the
      endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P <
      0.05). These results suggest that this variant of the GSTP1 may play a role in
      the manifestation of HP together with other independently and/or synergistically
      acting factors, particularly in primiparous pregnancy.

PMID- 14719183
TI  - Modulation of antithrombin-protease interactions by semisynthetic low-molecular
      weight heparins with different sulfation patterns.
AB  - Heparin, a natural glycosaminoglycan (GAG), is widely used for the treatment of
      thrombotic diseases. Most of its side effects are related to its ability to bind
      to different proteins, thus interfering with its target biological activity. To
      gain insight into structure-activity relationships, we investigated the
      interaction of a homogeneous series of sulfated polysaccharides, derived from
      controlled desulfation of a supersulfated low-molecular-weight heparin (LMWH)
      with the target enzymes human antithrombin (AT) and thrombin (T). In addition, we
      analyzed the activation process of the serpin AT against T and factor Xa (FXa). A
      nonlinear correlation between the strength of the AT-heparin complex and the
      polysaccharide sulfation degree was observed, whereas only a modest modulation of
      T binding to heparin occurred. The efficiency of the LMWH derivatives in
      activating AT toward the proteases was generally high for derivatives exhibiting
      a low dissociation constant. Only the supersulfated heparin showed a serpin
      activation ability higher than expected from the affinity studies. Examination of
      the sulfation pattern in the light of the above results suggests a key role of
      the substitution of the iduronic acid residue in the heparin-mediated serpin
      binding and activation processes. Indeed, sulfation at position 2 of the uronic
      acid is beneficial, whereas 2,3-disubstitution generates unfavorable contacts
      between the GAG and AT. Glucosamine sulfation at position 6 appears to grant
      increased catalytic efficiency. These results indicate that chemical modification
      of the heparin sulfation pattern can be used to modulate binding specificity and
      activity toward its biological targets.

PMID- 14719185
TI  - Macrophage activation syndrome--what's in a name!

PMID- 14719186
TI  - The possible clinical application of pharmacogenetics in rheumatology.

PMID- 14719187
TI  - Varus knee osteoarthritis: whence the varus?

PMID- 14719188
TI  - Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To examine whether the expression of intact CD1d, a critical molecule
      for the presentation of glycolipid antigens to natural killer T (NKT) cells, and
      its variants differs between patients with autoimmune diseases including
      rheumatoid arthritis (RA) and healthy subjects. Recently, we identified 8
      different CD1d variants, generated by alternative splicing. V1 lacking exon 4
      (CD1d without beta2 microglobulin, beta2m) and V2 lacking exons 4 and 5 (soluble
      CD1d) may be functional molecules, because the antigen binding sites (exons 2 and
      3) are intact. METHODS: Peripheral blood mononuclear cells (PBMC) from 44
      patients with autoimmune disease (RA 19, systemic lupus erythematosus, SLE 10,
      Sjogren's syndrome, SS 15) and 15 healthy controls were separated and
      complementary (c)DNA was prepared. The expression of intact CD1d on PBMC was
      detected by flow cytometry. Alternatively spliced CD1d variants were quantified
      by TaqMan PCR using polymerase chain reaction with confronting 2-pair primers
      (PCR-CTPP) based amplification. RESULTS: The mean (+/- SEM) transmembrane and
      beta2m binding site deleted CD1d mRNA level in 19 patients with RA (2.0 +/- 0.33)
      was significantly lower than in 15 controls (6.9 +/- 2.08; p < 0.05), whereas
      there were no differences in beta2m deleted variants and intact CD1d mRNA.
      CONCLUSION: Our findings suggest that low expression of soluble CD1d variants
      might play a role in the formation of symptoms or pathogenesis of RA.

PMID- 14719189
TI  - Elevated serum nitric oxide levels in patients with inflammatory arthritis
      associated with co-expression of inducible nitric oxide synthase and protein
      kinase C-eta in peripheral blood monocyte-derived macrophages.
AB  - OBJECTIVE: To quantify circulating nitric oxide (NO) levels and inducible NO
      synthase (iNOS) expression in peripheral blood monocyte-derived macrophages (PB
      MDM) from patients with inflammatory arthritis (IA) as a measure of disease
      activity, and to determine if there is a correlation between expression of iNOS
      and protein kinase C-eta (PKC-eta). METHODS: PB-MDM were isolated from whole
      blood of 20 patients with IA (14 rheumatoid arthritis and 6 peripheral
      spondyloarthropathies). Thirteen patients with osteoarthritis (OA) and 9 healthy
      individuals were controls. Serum NO levels were measured by indirect
      determination of nitrite and nitrate. Expression of PKC-eta and iNOS was
      investigated by reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis. RESULTS: Serum NO (189.9 +/- 49.7 microM) was significantly higher (p <
      0.0028) in IA patients than in controls (131.1 +/- 18.5 microM) or patients with
      OA (126.9 +/- 37.1 microM). IA patients with severe inflammation had highest
      levels of NO, while those with mild inflammation had normal levels of NO. RT-PCR
      showed that PB-MDM from IA patients with active disease co-expressed iNOS and PKC
      eta. This was observed in 15 out of 16 cases. All other groups with normal plasma
      NO expressed neither gene. CONCLUSION: Our findings show that elevated plasma NO
      levels were only present in IA patients with severe disease activity. We show for
      the first time a positive correlation between PKC-eta and iNOS expression in
      arthritis, supporting our earlier in vitro findings that PKC-eta expression was
      essential for lipopolysaccharide-mediated iNOS induction and NO production in
      human monocytes. PKC-eta may be important for the development of IA-induced iNOS
      positive phenotype in human PB-MDM.

PMID- 14719190
TI  - Value of antibodies to citrulline-containing peptides for diagnosing early
      rheumatoid arthritis.
AB  - OBJECTIVE: To compare the diagnostic values of antiperinuclear factor (APF),
      antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to
      discriminate between patients with and without rheumatoid arthritis (RA) and to
      determine the diagnostic value of anti-CCP used alone or with other tests.
      METHODS: Two hundred and seventy patients with early arthritis underwent
      standardized investigations in 1995-1997. The clinical utility of APF, AKA, and
      anti-CCP in first-visit sera was evaluated using receiver-operating
      characteristic curves. Combinations of anti-CCP with other laboratory tests were
      assessed by multiple logistic regression. RESULTS: Anti-CCP, APF, and AKA were
      not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was
      47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and
      AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM
      rheumatoid factor (RF) ELISA, and the latex test. CONCLUSION: Rheumatologists can
      routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and
      either AKA or anti-CCP ELISA) and can add a third or fourth test when the
      diagnosis remains in doubt.

PMID- 14719191
TI  - Rheumatic disease differentiation using immunoglobulin G sugar printing by high
      density electrophoresis.
AB  - OBJECTIVE: To determine whether immunoglobulin G (IgG) sugar printing using high
      density electrophoresis can be a diagnostic and prognostic test to rapidly
      differentiate early rheumatoid arthritis (ERA), rheumatoid arthritis (RA), and
      other rheumatic diseases from each other. METHODS: One hundred fifty-three
      patients with ERA/RA, psoriatic arthritis (PsA), early psoriatic arthritis (EPsA)
      ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), juvenile
      idiopathic arthritis (JIA), early undifferentiated seronegative arthritis (UA),
      and osteoarthritis (OA) were investigated. Samples of their serum IgG were
      purified, and sugars were released enzymatically and fluorophore-labelled, then
      subjected to high density electrophoresis, and relative quantities of each sugar
      were determined by optical density. RESULTS: Sugar prints of 9 sugars were
      compiled for each of the 9 disease groups. Specific disease-associated sugar
      changes were determined by comparison with OA. For example, agalactosylated
      structures were increased in ERA/RA and EPsA/PsA (p = 0.0001-0.004) and
      digalactosylated structures were decreased in PsA, AS, and JIA (p = 0.0001-0.04).
      When the disease groups were compared, each disease was characterized by a unique
      sugar print comprising 7 of the 9 sugars (p = 0.001-0.005); only g0fb and a1f
      were not associated. ERA/RA differed in the quantities of monogalactosyl and
      sialylated sugars (p = 0.006-0.007). The presence of agalactosyl sugars enabled
      correct prediction of RA in 71.2% of individuals, with a specificity of 84.2% and
      sensitivity of 50.0%. The area under the sensitivity versus specificity curve was
      0.7812. CONCLUSION: IgG sugar printing was found to be effective in
      differentiation of rheumatic diseases and can differentiate ERA and RA from each
      other and from other rheumatic diseases; and hence may constitute a relatively
      rapid diagnostic and prognostic test for patients presenting with arthritis.

PMID- 14719192
TI  - Interleukin 1 receptor antagonist inhibits localized bone formation in vivo.
AB  - OBJECTIVE: To test the in vivo effects of interleukin 1 receptor antagonist (IL
      1ra) on bone formation and tissue ingrowth using an implantable bone ingrowth
      chamber that can be infused with test solutions. METHODS: The bone ingrowth
      chamber was implanted in the proximal tibia of 10 mature NZW rabbits
      unilaterally. After an initial osseointegration period, the chambers were emptied
      of tissue and infused with either 0.05% bovine serum albumin (BSA) in phosphate
      buffered saline (PBS) or an IL-1ra solution for 4-week periods, which were
      separated by 4-week periods of no infusion. Tissue samples harvested from each
      chamber were snap-frozen and examined by histology and immunohistochemistry.
      RESULTS: The chambers were filled with longitudinally-oriented woven bone in a
      fibrovascular stroma during periods of infusion of 0.05% BSA in PBS or during
      periods without infusion. In contrast, infusion of IL-1ra for 4 weeks prevented
      tissue ingrowth in 4 of 6 chambers, and in 2 chambers exhibiting tissue ingrowth,
      bone formation was decreased. Bone formation remained at a lower level during the
      subsequent two 4-week periods without infusion after IL-1ra was discontinued,
      compared to samples prior to the IL-1ra treatment. CONCLUSION: The results showed
      that tissue ingrowth and bone formation were suppressed in an in vivo model by
      continuous infusion of IL-1ra at an early phase of tissue regeneration and
      differentiation.

PMID- 14719193
TI  - Increased plasma and joint tissue adrenomedullin concentrations in patients with
      rheumatoid arthritis compared to those with osteoarthritis.
AB  - OBJECTIVE: To elucidate the pathophysiological role of adrenomedullin (AM) in
      rheumatoid arthritis (RA), plasma AM concentration was measured in patients with
      RA and in healthy contols. The concentration of AM in joint fluid, synovial
      tissue, and articular cartilage of patients with RA and osteoarthritis (OA) were
      measured and compared. METHODS: Twenty-six patients with RA (aged 62 +/- 4 yrs,
      all female), 10 healthy controls (aged 57 +/- 5 yrs, all female), and 10 patients
      with OA (aged 68 +/- 8 yrs, all female) were studied. We measured plasma levels
      of total and mature AM by immunoradiometric assay and levels of AM in joint
      tissue by radioimmunoassay. RESULTS: Plasma levels of AM in patients with RA
      (18.35 +/- 6.9 fmol/ml) were found to exceed those in healthy controls (11.64 +/-
      2.8 fmol/ml). Moreover, plasma AM showed a significant positive correlation with
      plasma C-reactive protein (CRP). The correlation coefficient of total AM was
      0.685, and that of mature AM was 0.624. Similarly, AM levels in synovium and
      joint fluid in patients with RA were significantly higher than in OA. In
      contrast, AM levels in articular cartilage were found to be low, with no
      significant difference in levels between patients with RA and OA. CONCLUSION: The
      relation between plasma AM levels and plasma CRP in patients with RA suggests
      that plasma AM levels increase with the activity of RA. Moreover, AM levels in
      synovium and joint fluid of patients with RA were significantly higher than those
      of patients with OA. Thus, AM probably plays a part in the regulation of the
      inflammatory process of RA.

PMID- 14719194
TI  - Induction of autoantibodies during prolonged treatment with infliximab.
AB  - OBJECTIVE: To determine the frequency and correlates of autoantibody formation in
      patients with rheumatic diseases treated with infliximab in a routine clinical
      setting. METHODS: All patients receiving at least 5 infusions of infliximab, and
      with anticipated continuation, were prospectively evaluated for the development
      of the following antibodies: antinuclear antibody (ANA), anti-DNA, anti-Sm, anti
      RNP, anti-SSA and anti-SSB. Correlates with pharmacologic treatments, response to
      infliximab, and adverse events were assessed. RESULTS: Seventy-six percent of 42
      patients receiving prolonged treatment with infliximab developed new
      autoantibodies, and these persisted in 57%. The most common new autoantibody was
      ANA in 45%, followed by anti-DNA in 33%, anti-Sm in 31%, and anti-RNP in 29%. New
      autoantibody formation was associated with both a greater number of infusions (p
      = 0.015) and a higher total dose of infliximab infused (p = 0.047). No other
      treatment, disease characteristic, or loss of efficacy to infliximab
      discriminated between those developing antibodies compared to those without new
      antibody formation. No patient developed clinical signs of a new connective
      tissue disease. CONCLUSION: Autoantibody formation is seen commonly in patients
      receiving prolonged treatment with infliximab. Concomitant immunosuppressive
      treatments did not preclude the formation of antibodies. The clinical
      significance of antibody formation remains to be determined.

PMID- 14719195
TI  - Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody,
      and concomitant standard antirheumatic therapy for the treatment of rheumatoid
      arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis).
AB  - OBJECTIVE: This study, known as STAR (Safety Trial of Adalimumab in Rheumatoid
      Arthritis), evaluated the safety and efficacy of adalimumab (Humira), a fully
      human monoclonal tumor necrosis factor-alpha (TNF-a) antibody, when given with
      standard antirheumatic therapy in patients with active rheumatoid arthritis (RA)
      not adequately responding to such therapies. Standard antirheumatic therapy
      included traditional disease modifying antirheumatic drugs (DMARD), low dose
      corticosteroids, nonsteroidal antiinflammatory drugs (NSAID), and/or analgesics.
      METHODS: In this 24-week, double-blind, placebo-controlled study, 636 patients
      with RA were randomly assigned to receive adalimumab 40 mg subcutaneously (sc)
      every other week (n = 318) or placebo (n = 318) while continuing standard
      antirheumatic therapy. The frequencies of adverse events, serious adverse events,
      severe or life-threatening adverse events, adverse events leading to withdrawal,
      infection, or serious infection were the primary endpoints. Secondary endpoints
      were determined by American College of Rheumatology (ACR) response criteria.
      RESULTS: During the study, the majority of patients received concomitant
      traditional DMARD (83.5%) and/or corticosteroids, NSAID, and/or analgesics
      (97.3%). Overall, 56.0% of patients continued treatment with one, 23.6% with 2,
      and 3.9% with > or = 3 traditional DMARD. At 24 weeks, there were no
      statistically significant differences between the adalimumab and placebo groups
      in their respective rates of adverse events (86.5% vs 82.7%), serious adverse
      events (5.3% vs 6.9%), severe or life-threatening adverse events (11.9% vs
      15.4%), or those leading to withdrawal (2.8% vs 2.2%). There were also no
      statistically significant differences in the rates of infections (52.2% vs 49.4%)
      or serious infections (1.3% vs 1.9%) between the groups. The incidence and types
      of adverse events did not vary between adalimumab- and placebo-treated patients
      by the number of concomitant traditional DMARD (0, 1, or 2). Adalimumab-treated
      patients compared with placebo-treated patients achieved statistically superior
      ACR20 (52.8% vs 34.9%), ACR50 (28.9% vs 11.3%), and ACR70 (14.8% vs 3.5%)
      response rates at Week 24 (p < or = 0.001). CONCLUSION: This study demonstrated
      that addition of adalimumab 40 mg given sc every other week to concomitant
      standard antirheumatic therapy is well tolerated and provides significant
      improvements in signs and symptoms of RA. The data indicate that adalimumab is a
      safe and effective therapeutic option in patients with active RA who have an
      inadequate response to standard antirheumatic therapy, including one or more
      traditional DMARD, corticosteroids, NSAID, and analgesics.

PMID- 14719196
TI  - Efficacy and safety of leflunomide and predisposing factors for treatment
      response in patients with active rheumatoid arthritis: RELIEF 6-month data.
AB  - OBJECTIVE: The RELIEF investigation was a 48-week, multicenter, international
      study comprising 2 phases. Results from the first phase, a 24-week open-label
      cohort study that evaluated the safety and efficacy of leflunomide, as well as
      predisposing factors to treatment response, are reported here. METHODS: Patients
      received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily
      thereafter. All adverse events were documented. Efficacy variables were the
      European League Against Rheumatism (EULAR) response criteria using the Disease
      Activity Score (DAS 28) responder rate and the response rate according to
      American College of Rheumatology (ACR) criteria. At Week 24, baseline data were
      analyzed to determine predictive factors for treatment response. RESULTS: A total
      of 969 patients were entered in the trial. No adverse events that have not
      previously been seen with leflunomide were reported. Among 968 evaluable
      patients, 673 (69.6%) completed 24 weeks of treatment and were responders
      according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of
      treatment and were responders according to ACR 20%. Thus, there was a high
      correlation between the EULAR and ACR criteria in determining treatment response.
      In addition, 240 (24.8%) patients had a low DAS 28 (< or = 3.2) and 123 (12.7%)
      patients fulfilled the disease remission criteria (DAS 28 < 2.6) at the end of
      the study. CONCLUSION: This study demonstrates that leflunomide is well
      tolerated, with a safety profile similar to that seen previously in Phase III
      studies, and confirms the efficacy of leflunomide across a range of patient
      categories.

PMID- 14719197
TI  - Erosions develop rarely in joints without clinically detectable inflammation in
      patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To study whether clinically observed tenderness and/or swelling of a
      wrist joint over the first 3 years after diagnosis predict the development of
      erosions in radiographs of the same joint at 5 years in patients with early
      rheumatoid arthritis (RA). METHODS: A total of 58 patients with recent onset RA
      were enrolled in a prospective RA study at Jyvaskyla Central Hospital in 1983-85.
      Physical examination including joint counts was performed 6 times over 3 years
      (at 0, 6, 12, 18, 24, and 36 mo). Radiographs of hands and feet taken at the 5
      year visit were scored according to the Larsen method (0-1 = non-erosive; 2-5 =
      erosive). At each visit, the wrist joints were assessed for tenderness (0/1) and
      swelling (0/1). A frequency (ranging from 0 to 6) was calculated for 4
      inflammation categories tenderness, swelling, tenderness or swelling, and
      tenderness and swelling over the 3 years. Percentages of wrist joints with
      erosions on the 5-year radiographs were calculated for the frequency groups 0, 1,
      2-3, and 4-6 of each category. Two patients died, and 5 wrists were erosive at
      baseline. Thus the data for 107 wrist joints of 54 patients were available for
      analyses. RESULTS: A statistically significant correlation was seen in the
      frequency of clinical inflammation and the development of erosions. Only one
      (3.3%) wrist with no tenderness in 6 examinations over the first 3 years
      developed erosions over 5 years, while 13 (59.1%) wrists that were tender 4-6
      times in 6 examinations developed erosions. The corresponding percentages were
      4.4% and 50.0% for wrists with swelling, 3.4% and 51.6% for wrists with
      tenderness or swelling, and 6.1% and 75.0% for wrists with tenderness and
      swelling. CONCLUSION: Radiographic erosions develop rarely without preceding
      clinically detectable inflammation in the joints of patients with early RA.

PMID- 14719198
TI  - Prognostic factors for joint destruction in rheumatoid arthritis: a prospective
      longitudinal study of 318 patients.
AB  - OBJECTIVE: To quantify articular damage and to investigate prognostic factors for
      joint damage progression in rheumatoid arthritis (RA). METHODS: RA patients
      satisfying the 1987 American College of Rheumatology criteria and with disease
      duration under 5 years were sampled from the EURIDISS longitudinal cohort study
      in Norway, The Netherlands, and France. Hand radiographs were assessed at
      baseline and at 2 to 3 year followup using Sharp score modified by van der
      Heijde. Assessment of erosion and joint space narrowing, performed in sequential
      order by a single reader blinded to patients' characteristics, had high
      intraobserver reproducibility (intraclass correlation coefficient 0.98-0.99).
      Baseline prognostic factors were analyzed in a multivariate linear regression
      model. RESULTS: A total of 318 patients with RA aged 52.4 years (70.4% were
      female) and with a mean 2 years' disease duration at baseline were followed over
      30 months. Median (quartiles) baseline and followup modified Sharp scores were 3
      (0-11) and 9 (1-27), respectively, with 35.8% and then 22.3% of patients with no
      radiological damage. Controlling for age, sex, and country, the final joint
      damage was predicted by baseline modified Sharp score, rheumatoid factor
      positivity, time from disease diagnosis, patient global health assessment, and
      erythrocyte sedimentation rate, and by followup duration, explaining 76.8% of the
      outcome variance. CONCLUSION: This multinational study confirmed the prognostic
      role in RA of a set of features previously identified in smaller cohorts. It
      indicates which disease characteristics should be focused on in the early years
      of RA to identify patients at higher risk of developing severe disease and who
      are candidates for aggressive therapy.

PMID- 14719199
TI  - Reduced bone mineral density in early rheumatoid arthritis is associated with
      radiological joint damage at baseline and after 2 years in women.
AB  - OBJECTIVE: Data suggest that reduced bone mass may be associated with
      radiological damage in rheumatoid arthritis (RA). We investigated if patients
      with reduced bone mineral density (BMD) at onset of RA had more radiological
      damage at onset and after 2 years than patients with normal BMD. METHODS: BMD at
      lumbar spine and hip was measured in 204 patients with recent RA at presentation.
      At baseline and after 2 years, radiographs of hands and forefeet were evaluated
      according to the Larsen method. At the same time-points, Disease Activity Score
      (DAS 28) and functional disability (the Stanford Health Assessment Questionnaire,
      HAQ) were assessed. RESULTS: The 134 women and 70 men had a mean age of 55 and 61
      years, respectively. Reduced bone mass (RBM, Z score < or = 1.0 SD) in at least
      one site was found in 46.0% of women and 62.5% of men. T and Z scores correlated
      significantly with Larsen scores both at baseline and after 2 years for the total
      patient cohort. Calculated separately for the sexes, significant correlations
      were found only for women. Women but not men with reduced bone mass and
      osteoporosis had higher Larsen scores at baseline and after 2 years than those
      without. From a stepwise multiple logistic regression analysis Z score trochanter
      and baseline C-reactive protein were selected as independent predictors of joint
      damage, measured as proportion over the median Larsen scores. This model could
      explain about 25% of the "variance" in outcome (Nagelkerke R2 = 0.27).
      CONCLUSION: Reduced BMD at onset of RA in women was associated with a higher
      Larsen score at baseline and after 2 years, indicating that the development of
      reduced bone mass and joint destruction in RA may have a common
      pathophysiological mechanism.

PMID- 14719200
TI  - Increased estrogen formation and estrogen to androgen ratio in the synovial fluid
      of patients with rheumatoid arthritis.
AB  - OBJECTIVE: It has been proposed that physiologic levels of estrogens stimulate
      immune responses whereas androgens suppress inflammatory reactions. Thus,
      prevalence of synovial androgens relative to estrogens would be favorable in
      rheumatoid arthritis (RA). We investigated synovial fluid (SF) concentrations of
      several estrogens and androgens and conversion products of the sex steroid
      precursor dehydroepiandrosterone (DHEA) in supernatants of mixed synoviocytes.
      METHODS: SF steroid concentrations were measured by high performance liquid
      chromotography and mass spectrometry in 12 patients with RA and 8 subjects with
      traumatic knee injury (noninflammatory controls). Conversion of DHEA to
      downstream hormones was measured by thin-layer chromatography and phosphorimaging
      detection in 3 patients with RA and 3 patients with osteoarthritis (OA). RESULTS:
      Overall, SF concentration of free estrogens tended to be higher in RA patients
      versus controls (p < 0.06). Molar ratio of free SF estrogens/free SF androgens
      was elevated in RA compared to controls (1.17 +/- 0.32 vs 0.29 +/- 0.08, without
      unit; p = 0.017). The free SF concentration of the precursor androstenedione was
      significantly higher in RA patients than in controls (104.6 +/- 32.6 vs 30.4 +/-
      0.4 ng/ml; p = 0.011), and SF estrone the aromatase conversion product of
      androstenedione was also elevated in RA compared to controls (13.6 +/- 2.6 vs 6.6
      +/- 0.8 ng/ml; p = 0.035). The biologically active estrogen derivatives, 16a
      hydroxyestrone and 4-hydroxyestradiol, were both higher in RA compared to
      controls (p = 0.085 and p = 0.044, respectively). In mixed RA synoviocytes, DHEA
      conversion yielded high local levels of 17beta-estradiol (708 pmol/l = 0.193
      ng/ml) compared to testosterone (88 pmol/l = 0.026 ng/ml). CONCLUSION: SF levels
      of estrogens relative to androgens are significantly elevated, while those of
      androgens are markedly reduced, in patients with RA compared to controls. This
      imbalance is most probably due to increased aromatase activity. Thus, an
      available steroid precursor, such as DHEA, may be rapidly converted to
      proinflammatory estrogens in the synovial tissue, which may in turn stimulate the
      inflammatory process in patients with RA.

PMID- 14719201
TI  - Neuron specific enolase concentration is increased in serum and decreased in
      platelets of patients with active systemic sclerosis.
AB  - OBJECTIVE: To determine frequency, origin, and clinical associations of elevated
      serum neuron specific enolase (NSE) in systemic sclerosis (SSc). METHODS: Serum
      was obtained from 75 patients with SSc, 20 systemic lupus erythematosus, 8
      polymyositis, 10 idiopathic interstitial lung disease, and 10 healthy volunteers.
      NSE status was determined in serum (in all individuals) and in platelet lysate
      (in volunteers and 30 patients with SSc). RESULTS: Elevated serum NSE (mean 22.6
      ng/ml, range 12.1-68.2 ng/ml) was observed in 26 patients with SSc (34.6%). Those
      with diffuse SSc had higher serum NSE than those with limited disease (16.5 +/-
      13.4 vs 9.6 +/- 5.0 ng/ml, p = 0.006). No association was found between serum NSE
      and lung or esophagus involvement. Patients with long-standing disease had lower
      serum NSE than those with early disease (10.8 +/- 7.3 vs 16.1 +/- 13.6 ng/ml, p =
      0.05). Serum NSE was 19.4 +/- 13.0 ng/ml in patients with total skin score (TSS)
      > 20, 8.3 +/- 2.1 ng/ml in patients with TSS < 5, and 6.0 +/- 3.1 ng/ml in
      volunteers (p = 0.01). NSE platelet lysate concentration was 3.6 +/- 2.9 ng/ml in
      patients with TSS > 20, 12.4 +/- 4.1 ng/ml in those with TSS < 5, and 14.1 +/-
      6.5 ng/ml in healthy individuals (p < 0.001). Volunteers and SSc patients with
      low TSS had comparable S/PL-NSE index (serum/platelet lysate NSE concentration)
      (0.42 +/- 0.16 and 0.75 +/- 0.33, respectively), both lower than SSc patients
      with high TSS (7.45 +/- 5.57) (p < 0.001). CONCLUSION: Elevated serum NSE was
      observed in one-third of SSc patients but not in other autoimmune rheumatic
      diseases. The inverse relationship between serum and platelet lysate NSE
      concentration suggests platelet activation as the origin of high serum NSE in
      SSc. NSE S/PL was the best discriminatory variable between healthy volunteers and
      SSc patients as well as between patients with high and low TSS. High serum NSE
      and high NSE-S/PL index seemed to be associated with SSc disease activity.
      Further work is warranted to investigate a possible role for this marker in
      assessing disease activity and therapy response.

PMID- 14719202
TI  - Autoantibodies to tissue transglutaminase in Sjogren's syndrome and related
      rheumatic diseases.
AB  - OBJECTIVE: Sjogren's syndrome (SS) has been reported in up to 15% of patients
      with biopsy proven celiac disease (CD). The diagnosis of CD in the setting of SS
      and other systemic rheumatic diseases can be difficult because they are often
      associated with a number of gastrointestinal symptoms and diseases. Although the
      diagnosis of CD is often confirmed by a small bowel biopsy, marker autoantibodies
      directed against the endomysium of transitional epithelium (EMA) and tissue
      transglutaminase (tTG) are highly correlated with biopsy-proven disease and serve
      as a valuable screening test. We used an IgA-anti-tissue transglutaminase
      antibody (anti-tTG) ELISA to assess the prevalence of anti-tTG in an unselected
      cohort of patients with SS and other systemic rheumatic diseases. METHODS: Sera
      from 50 patients with SS, 50 with systemic lupus erythematosus (SLE), 50 with
      rheumatoid arthritis (RA), 30 with systemic sclerosis (SSc), and 50 healthy
      controls were tested for autoantibodies to tTG. A comparison group of 40 sera
      from patients with biopsy-confirmed CD was also included. IgA anti-tTG was
      measured by a commercially available ELISA kit (Inova, San Diego, CA) that
      employs purified tTG. RESULTS: Six of the 50 (12%) IgA sufficient SS patients had
      anti-tTG compared to 2 (4%) normal sera, 3 (6%) SLE, 2 (7%) SSc, and 1 (2%) RA.
      By comparison, in the CD cohort, 33 (83%) had anti-tTG. Five of 6 SS patients
      with anti-tTG had symptoms, signs, or small bowel biopsy findings consistent with
      a diagnosis of CD. IgA anti-tTG and EMA were accompanied by other IgA
      autoantibodies in SS sera. CONCLUSION: Anti-tTG ELISA is a reliable method to
      indicate a coexisting diagnosis of CD in patients with SS. Interestingly, the
      frequency of false positive tTG tests in any of the systemic rheumatic diseases
      is not significantly greater than in controls. Further, our study shows that anti
      tTG is more prevalent in SS than in other systemic rheumatic diseases. The tTG
      ELISA may be used as a screening test to identify patients with SS who are at
      risk and require further evaluation for the presence of CD.

PMID- 14719203
TI  - Intravenous colchicine for treatment of patients with familial Mediterranean
      fever unresponsive to oral colchicine.
AB  - OBJECTIVE: To evaluate the efficacy and safety of weekly intravenous (IV)
      colchicine, in addition to oral colchicine therapy, in a subset of patients with
      familial Mediterranean fever (FMF) unresponsive to oral colchicine prophylaxis.
      METHODS: Thirteen patients with frequent FMF attacks, despite oral doses of 2-3
      mg/day colchicine, were treated with weekly IV injections of 1 mg colchicine for
      12 weeks in an open-label pilot study. Patients were evaluated periodically for
      the number and severity of their attacks, use of analgesics, and erythrocyte
      sedimentation rate (ESR). RESULTS: A 50% reduction in attack frequency and attack
      severity in at least one site was achieved by 10 and 6 of the 13 study patients,
      respectively (p < 0.001 and p < 0.01). Mean number of abdominal attacks declined
      significantly from 4.2 +/- 3.0 per patient at baseline to 1.9 +/- 2.6 attacks at
      the end of the third month of the study (p = 0.0002). The mean severity of
      abdominal attacks declined from a baseline of 6.1 +/- 0.95 to 3.9 +/- 2.8 after 3
      months (p = 0.02). Comparable significant change was observed in chest attacks,
      ESR, and number of analgesic tablets used. Joint attacks were unrelieved during
      the study period. The treatment was safe and well tolerated, without side
      effects. CONCLUSION: Treatment with weekly IV colchicine injections in addition
      to oral colchicine therapy is effective and safe in patients with FMF refractory
      to oral colchicine.

PMID- 14719204
TI  - Polymyalgia rheumatica is not seasonal in pattern and is unrelated to parvovirus
      b19 infection.
AB  - OBJECTIVE: To prospectively analyze seasonal distribution in the onset of
      symptoms of polymyalgia rheumatica (PMR) and its relationship to parvovirus B19
      infection. METHODS: Over a 4-year period (September 1997 to September 2001), 68
      patients were prospectively diagnosed with PMR in an outpatient rheumatology
      department, of which only 55 patients (38 women, 17 men) aged 50 to 90 years
      (mean 74.1 +/- 8.1) were able to specify the month of onset of symptoms. During
      the last year parvovirus B19 IgM serologies were determined in all new cases.
      RESULTS: No significant seasonal variation in disease onset was observed during
      the 4-year period; 17 cases were observed in spring, 10 in summer, 15 in autumn,
      and 13 in winter (p = 0.625). Nevertheless, almost 50% of all cases of PMR were
      diagnosed in the months of May, February, and August. All of the evaluated
      patients (14 of 14) had negative parvovirus B19 IgM serologies. CONCLUSION: Onset
      of symptoms in PMR is unrelated to seasonal pattern. Yet almost 50% of cases
      occurred in the months of May, February, and August. Parvovirus B19 infection was
      unrelated to the onset of PMR.

PMID- 14719205
TI  - Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label
      trial.
AB  - OBJECTIVE: To examine the efficacy of thalidomide in the treatment of active
      ankylosing spondylitis (AS) refractory to conventional therapies. METHODS: In a 6
      month open-label trial, we studied 13 men with different subtypes of active AS: 3
      juvenile AS, 9 adult AS, and one AS with psoriasis. All patients were resistant
      to conventional nonbiologic therapies including nonsteroidal antiinflammatory
      drugs, sulfasalazine, and methotrexate. After 3 months' observation on a
      preexisting regimen, oral thalidomide was added, starting at 100 mg/day for 1
      week, then 200 mg/day for another 23 weeks. Outcome measures included the Bath AS
      Disease Activity Index (BASDAI), Functional Index (BASFI), Global Index (BAS-G),
      IgA, C-reactive protein (CRP), and eosinophil sedimentation rate (ESR). Response
      to treatment was defined following the Ankylosing Spondylitis Assessment
      criteria. RESULTS: Three patients withdrew due to rash. Two patients were lost to
      followup due to lack of efficacy. Eight patients completed the trial. Four
      patients attained > 50% improvement (2 juvenile AS, 1 peripheral AS, and 1
      psoriatic arthritis). Four patients attained > 20% improvement (2 axial and 2
      peripheral AS). Total response rate accordingly was 80% (8/10). Mean BASDAI
      improved significantly from baseline to Week 24 (4.97 vs 3.1; p = 0.0156). Mean
      BASFI improved from baseline to Week 24 (5.24 vs 3.06; p = 0.0078), and BAS-G
      from 6.02 to 3.21 (p = 0.0078). Significant laboratory improvements were found in
      ESR (from 69.5 to 34.2 mm/h; p = 0.0156), but not CRP (from 6.08 to 3.01 mg/dl; p
      = 0.078) or IgA (from 496 to 505 mg/dl; p = 0.375). Dry mouth, constipation, and
      dizziness were common, but no severe adverse events were found. CONCLUSION:
      Thalidomide is a promising treatment for patients with active AS who are
      resistant to conventional therapies other than biologics.

PMID- 14719206
TI  - Undifferentiated spondyloarthropathies in Brazilians: importance of HLA-B27 and
      the B7-CREG alleles in characterization and disease progression.
AB  - OBJECTIVE: To analyze the profile of the HLA-B27 and B7 cross-reactive group
      (CREG) alleles and the role of these markers in disease characterization and
      progression in patients with undifferentiated spondyloarthropathies (uSpA).
      METHODS: A total of 80 patients with a diagnosis of uSpA (40 HLA-B27 positive and
      40 HLA-B27 negative) were prospectively studied for 2 years. The control group
      consisted of 66 HLA-B27 positive and 112 HLA-B27 negative individuals without a
      history of seronegative SpA. HLA-B alleles were typed at low (B7-CREG alleles,
      i.e., B*7, B*54, B*55, B*56, B*40, B*42) or high resolution (B*27 alleles) using
      polymerase chain reaction-amplified DNA hybridized with sequence-specific
      oligonucleotide probes. RESULTS: HLA-B*2705 was the most frequent allele,
      observed in 92.5% of the patients and in 77% of the controls, followed by the HLA
      B*2702, observed in 5% of the patients and in 12% of the controls. HLA-B*2704 was
      observed in only one patient (2.5%), and was absent in the control population.
      HLA-B*2703 (6%) and HLA-B*2707 (5%) alleles were observed only in controls. No
      associations between HLA-B*27 alleles or B7-CREG alleles and any specific
      manifestation of uSpA were observed. HLA-B27 positive patients more frequently
      presented juvenile onset SpA (p = 0.002) and progression to ankylosing
      spondylitis (AS) (p = 0.03) than did HLA-B27 negative patients. The B7-CREG
      alleles were observed in 5% of the HLA-B27 positive uSpA group, in 25% of the HLA
      B27 negative uSpA group, in 7% of the HLA-B27 positive controls, and in 13% of
      the HLA-B27 negative controls; a significant association was observed between the
      presence of the B7-CREG and the HLA-B27 negative uSpA group (p = 0.012).
      CONCLUSION: The frequency of the HLA-B*2705 allele among the B27 positive uSpA
      patients of this series was closely similar to that reported for patients with
      ankylosing spondylitis (AS). The presence of HLA-B*27 alleles was associated with
      the progression to AS, and the presence of B7-CREG was associated with uSpA in
      the HLA-B27 negative group.

PMID- 14719207
TI  - Clinical and genetic aspects of psoriatic arthritis "sine psoriasis".
AB  - OBJECTIVE: To characterize the clinical pattern of psoriatic arthritis (PsA) sine
      psoriasis. METHODS: Fifty-seven patients (31 men, 26 women, mean age 46.32 +/-
      14.12 yrs) with undifferentiated spondyloarthropathy (SpA) were studied. Two
      subsets were defined: (1) 21 patients with familial psoriasis (12 men, 9 women,
      mean age 49.29 +/- 14.17 yrs); (2) 36 patients without familial psoriasis (19
      men, 17 women, mean age 44.58 +/- 14.00 yrs). The prevalence of the following
      clinical variables was evaluated: low back pain, enthesopathy, dactylitis, distal
      interphalangeal (DIP) arthritis, spinal involvement, and discitis. In all
      patients the following HLA haplotypes were tested: B7, B13, B17, B18, B27, B38,
      Cw6, and DR7. RESULTS: Dactylitis and DIP arthritis were markedly present in the
      articular subset with familial psoriasis (p < 0.0001) that also showed a high
      frequency rate of HLA-Cw6 (p < 0.0001 vs controls and patients without familial
      psoriasis). HLA-B27 was markedly frequent in patients without familial psoriasis
      (p < 0.0001 vs controls and p = 0.019 vs patients with familial psoriasis). In
      addition, in patients with familial psoriasis the log-linear model showed that
      the presence of HLA-Cw6 was related to the presence of DIP arthritis as well as
      dactylitis (likelihood ratio chi-square change of 5.891 and p = 0.015).
      CONCLUSION: A subset of patients with PsA "sine psoriasis" is identified by the
      occurrence of a SpA with dactylitis and/or DIP arthritis, presence of HLA-Cw6,
      and familial psoriasis in first or second-degree relatives.

PMID- 14719208
TI  - Epidemiology of psoriatic arthritis in northwest Greece, 1982-2001.
AB  - OBJECTIVE: To investigate the frequency and distribution of psoriatic arthritis
      (PsA) in a defined area of Northwest Greece, with a population of about 500,000
      inhabitants. METHODS: Cases were recorded from in- and outpatients referred to
      the Rheumatology Clinics of the Ioannina University Hospital and the Ioannina
      General Hospital, and from patients referred to private rheumatologists
      practicing in the study area. All patients recorded between January 1, 1982, and
      December 31, 2001, resident in the study area, were included. The study area
      included the Department of Epirus and the northern part of the Department of
      Ionian Islands. Diagnosis was based on the European Spondylarthropathy Study
      Group criteria. Incidence and prevalence rates were calculated as number of cases
      per 100,000 inhabitants. Population data were based on the National Census.
      RESULTS: The age-adjusted prevalence of PsA was 56.6 cases per 100,000 adults on
      December 31, 2001. A total of 221 new cases were diagnosed during the study
      period, giving an age-adjusted mean incidence rate of 3.02 cases per 100,000
      adults. There was no significant difference observed between men and women. The
      peak of incidence was observed in the age group 45-64 years. Incidence of
      diagnosed PsA increased during the study period. CONCLUSION: The incidence and
      prevalence of PsA in Northwest Greece was roughly half that reported in studies
      from the US and Northern Europe. This frequency tended to increase in the last
      decade.

PMID- 14719209
TI  - Operational definitions and observer reliability of the plain radiographic
      features of psoriatic arthritis.
AB  - OBJECTIVE: To determine the standardization and the observer reliability of
      potentially diagnostic plain radiographic features of psoriatic arthritis (PsA).
      METHODS: Radiographic features were chosen on the basis of a systematic review of
      the literature. One hundred sixty-four radiographs from 62 patients were selected
      from various sources by a musculoskeletal radiologist. Radiographs were read
      independently by 2 observers (WJT, PSH) and scored for the presence or absence of
      each evaluated feature. Cohen's kappa was used to determine observer agreement
      beyond chance, and the accuracy of each observer (with reference to the
      radiologist's judgment) was determined by likelihood ratios. RESULTS: The 2
      observers demonstrated similar accuracy, although WJT tended to be more accurate
      for items classed as absent and PSH more accurate for items classed as present.
      The following features showed sufficient reliability to be reasonably included in
      further testing of their discriminatory value (intra- and interobserver kappa
      values): marginal syndesmophyte (0.68, 0.69), non-marginal syndesmophyte (0.75,
      0.59), paravertebral ossification (0.89, 0.79), destructive discovertebral lesion
      (0.85, 0.65), Romanus lesion (0.64, 0.43), sacroiliitis (0.99, 0.86), entheseal
      erosion (0.80, 0.71), entheseal ossification (0.69, 0.76), distal interphalangeal
      erosive disease (0.58, 0.52), joint osteolysis (0.62, 0.47), juxtaarticular bony
      proliferation (0.43, 0.42), bony ankylosis (0.53, 0.54), tuft osteolysis (0.51,
      0.36). The features that showed inadequate reliability were: loss of cortical
      definition of terminal tuft (0.33, 0.31) and periosteal new bone formation (0.42,
      0.03). CONCLUSION: A number of plain radiographic features of PsA have sufficient
      reliability to justify inclusion in diagnostic classification criteria sets for
      further testing.

PMID- 14719210
TI  - Imaging skeletal pathology in mutant mice by microcomputed tomography.
AB  - OBJECTIVE: We describe the utility of microcomputed tomography ( micro CT) for
      imaging skeletal abnormalities in rodent model systems. For the purpose of
      illustration, the progressive ankylosis (ank) mutant was selected. ank mice
      develop prominent articular and periarticular calcifications at multiple
      anatomical sites, including paws, elbows, knees, and vertebrae. METHODS:
      Forelimbs, hindlimbs, and proximal tail vertebrae of 4-month-old female ank/ank
      mice were scanned at 15 micro m resolution using a SkyScan 1072 micro CT
      instrument and images were generated using Analyze 4.0 software. RESULTS: This
      technique was able to show, in 3-dimensional images, the abnormal calcification
      of ank/ank mice, which was readily observed within joint surfaces, on periosteal
      surfaces, sesamoid bones, menisci, and joint capsules, as well as other
      periarticular ligamentous structures. CONCLUSION: As illustrated by the example
      of the progressive ankylosis mutant, micro CT represents a powerful emerging tool
      for identifying and monitoring the progression of developmental or acquired
      skeletal abnormalities within rodent models.

PMID- 14719211
TI  - Human brucellosis: do we need to revise our therapeutic policy?
AB  - OBJECTIVE: To identify risk factors of relapse among patients with osteoarticular
      brucellosis. METHODS: In a prospective cohort study, we investigated 90 patients
      with diagnosis of brucellosis, as established by clinical picture and at least 4
      fold rise in antibody titer. Osteoarticular involvement was defined by
      inflammatory signs and radiographic changes. Thirty-five patients received
      combination therapy of 2 drugs (rifampicin + cotrimoxazole or doxycycline), while
      55 patients received a combination of 3 drugs (streptomycin + rifampicin +
      doxycycline). Monthly followup comprised clinical and laboratory examinations
      (seroagglutination, IgG, IgM antibody titers). Recovery of patients was based on
      clinical improvement and seroagglutination antibody titer < or = 1:80, as well as
      negative results for IgG and IgM antibody titers. Incidence of relapse was
      recorded during the 2 year period of followup after finishing the course of
      treatment. RESULTS: All patients continued treatment beyond the usual 6 week
      period previously recommended. Relapse occurred in 59.3% in patients who received
      treatment for 5 months or less, while relapse occurred in 7.9% among those who
      received treatment for more than 5 months (p < 0.001). Sixty percent of patients
      who received combination therapy of 2 drugs had relapse, while there was no
      relapse in patients who received 3 drugs in combination (p < 0.001). Logistic
      regression analysis identified duration of treatment < 5 months and IgG level
      (above 50 U/ml) as independent predictors for relapse; the predictivity of the
      model was 85.6%. CONCLUSION: Extending treatment for longer than previously
      recommended (6 weeks) resulted in an incidence of relapse significantly lower
      than for shorter courses of treatment. IgG antibody in addition to
      seroagglutinating antibody titers are useful for serological followup of patients
      with brucellosis.

PMID- 14719212
TI  - Effect of intermittent cyclical etidronate therapy on corticosteroid induced
      osteoporosis in Japanese patients with connective tissue disease: 3 year
      followup.
AB  - OBJECTIVE: A 3 year prospective randomized study was conducted to clarify the
      efficacy of intermittent cyclical etidronate therapy on corticosteroid induced
      osteoporosis. METHODS: A group of 102 Japanese patients were enrolled, each
      taking > 7.5 mg of prednisolone daily for at least 90 days. Patients were
      randomly divided into 2 treatment groups: Group E (etidronate) took 200 mg
      etidronate disodium per day for 2 weeks with 3.0 g calcium lactate and 0.75
      microg alphacalcidol daily; Group C (control) took 3.0 g calcium lactate and 0.75
      microg alphacalcidol daily. Outcome measurements included changes from baseline
      in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral
      fractures at 48 and 144 weeks. RESULTS: The mean (+/- SD) lumbar spine BMD
      increased 3.7 +/- 5.6% (p < 0.01) and 1.5 +/- 4.1% (NS) from baseline at 48 weeks
      and 4.8 +/- 6.9% (p < 0.005) and 0.4 +/- 5.0% (NS) from baseline at 144 weeks in
      Group E and Group C, respectively. The improvement of BMD in Group E was
      significantly greater than in Group C at 144 weeks (p < 0.01). In 3 subgroups,
      men and premenopausal and postmenopausal women, the postmenopausal women showed
      the greatest improvement. Mean percentage change in this subgroup was 10.1 +/-
      8.0% and 1.35 +/- 6.4% in Group E and Group C, respectively. We noted that 2
      patients in Group C had new vertebral fractures, whereas no fractures were
      observed in Group E. CONCLUSION: These results indicate that intermittent
      cyclical etidronate therapy is effective for the prevention and treatment of
      corticosteroid induced osteoporosis in patients with connective tissue diseases.

PMID- 14719213
TI  - Nonsteroidal antiinflammatory drug toxicity monitoring and safety practices.
AB  - OBJECTIVE: Nonsteroidal antiinflammatory drug (NSAID) related gastrointestinal
      (GI) and renal adverse events are commonly reported. Although published
      guidelines recommend periodic laboratory monitoring, NSAID safety practices of
      physicians have not been investigated at a population level. We examined the
      associations of physician specialty and patient characteristics with NSAID safety
      practices. METHODS: Using administrative data and medical record review from a
      regional managed care organization, we studied a retrospective cohort of 373
      frequent NSAID users (> or = 3 consecutive NSAID prescriptions and > or = 1 month
      of continuous NSAID use and followup). NSAID safety measures included: complete
      blood count (CBC) testing, creatinine testing, use of GI cytoprotective agents,
      and lack of simultaneous prescriptions for different NSAID (NSAID overlap).
      RESULTS: The mean duration of cumulative NSAID use was 14.4 +/- 7.7
      months/patient, patient age was 62.0 +/- 11.4 years, and 63% were women. About
      two-thirds of patients received CBC (238, 63.8%) and creatinine monitoring (263,
      70.5%), one-third (120, 32.2%) were prescribed cytoprotective agents, and one
      fourth (97, 26%) had at least one NSAID overlap. After multivariable adjustments,
      concomitant use of disease-modifying antirheumatic drugs (OR 2.5, 95% CI 1.1
      5.8), longer NSAID exposure (OR 1.3, 95% CI 1.1-1.4), and a greater number of
      physician visits/year (OR 1.1, 95% CI 1.0-1.2) were significantly associated with
      receipt of a CBC. A history of hypertension (OR 2.0, 95% CI 1.2-3.2), longer
      NSAID exposure (OR 1.3, 95% CI 1.2-1.4), and more physician visits/year (OR 1.1,
      95% CI 1.0-1.2) were significantly associated with serum creatinine testing.
      Rheumatologists, and to a lesser extent internists, trended toward more NSAID
      toxicity monitoring than family/general practitioners. However, family/general
      practitioners and internists were more likely to monitor creatinine than
      rheumatologists among patients with renal risk factors. CONCLUSION: While
      rheumatologists and internists trended toward more CBC and creatinine testing,
      visit frequency, duration of NSAID use, and comorbidities were the factors most
      consistently associated with safety monitoring.

PMID- 14719214
TI  - Prevalence of lower extremity pain and its association with functionality and
      quality of life in elderly women in Australia.
AB  - OBJECTIVE: To determine the prevalence of self-reported lower extremity pain and
      the impact on functionality and quality of life in a population based study of
      elderly women in Western Australia. METHODS: One thousand four hundred eighty-six
      women, 6.2% of 24,800 women aged over 70 in Perth, were recruited. An index of
      relative socioeconomic disadvantage (SES) was derived from postcode. Self
      reported lower extremity pain at the hip, knee, and foot was collected by
      questionnaire. The frequency of lower extremity pain was classified into 5
      groups. Mobility was measured by the Timed Up and Go Test (TUG). Quality of life
      was measured using the Medical Outcome Study Short Form 36 (SF-36) summary
      statistics: physical and mental component scores (PCS and MCS). RESULTS: The
      prevalence of women reporting any hip, knee, and foot pain was 39%, 52%, and 34%
      respectively. Fourteen percent experienced pain at all sites whereas 28% had no
      pain. There was no age difference between the various pain groups. Women with
      more pain were heavier and had higher BMI scores. At all lower limb sites, women
      with more frequent pain had reduced mobility and lower quality of life as
      measured by TUG, PCS, and MCS. For the TUG test, significant determinants in
      stepwise regression were age, BMI, knee and hip pain. For the SF-36 PCS,
      significant predictors were age, SES, BMI, and foot, knee, and hip pain. For the
      SF-36 MCS, SES and foot pain were significant predictors. CONCLUSIONS: Our
      results confirm the high prevalence of lower extremity pain in elderly women in
      Australia. Lower extremity pain significantly reduced both physical and mental
      aspects of the quality of life as well as mobility. In view of the availability
      of effective interventions to reduce joint pain, more aggressive intervention in
      the most disabled is indicated.

PMID- 14719215
TI  - Consultation and the outcome of shoulder-neck pain: a cohort study in the
      population.
AB  - OBJECTIVE: Despite the high prevalence of shoulder-neck pain in the community,
      and the fact that it is commonly a persistent and disabling condition, only a
      minority of sufferers seek medical help. We investigated the association between
      primary care consultation and subsequent outcome in a cohort of shoulder-neck
      pain sufferers. METHODS: A population with unilateral shoulder-neck pain was
      identified by a questionnaire mailed to 4002 adults randomly selected from the
      register of one family practice. Subjects were asked to shade areas of pain on a
      blank manikin, and give demographic details and scales of pain, anxiety, and
      depression. For the following 2 years, general practitioner (GP) consultations
      for shoulder and neck problems were determined using the practice database. The
      persistence of pain and degree of shoulder-specific disability, as well as
      general health status using the Medical Outcome Study Short Form-36 (SF-36), were
      assessed by means of a second postal survey at 2 years' followup. RESULTS: Three
      hundred four subjects (11.7% of questionnaire responders) had unilateral shoulder
      neck pain at baseline, and 224 were included in the study analyses. Of these, 47
      (21%) consulted their GP for shoulder-neck problems over the 2 years. Of the 47
      consulters, 36 (77%) reported shoulder-neck pain at followup; this was a higher
      percentage than that for nonconsulters (RRadjusted = 1.3). Among all subjects
      with persistent shoulder-neck pain, consulters were more likely than
      nonconsulters to have shoulder related disability at followup (RRadjusted = 1.6).
      On average, consulters had more pain and lower levels of physical functioning at
      followup than nonconsulters as measured by the SF-36. CONCLUSION: The minority of
      shoulder-neck pain sufferers who consult a primary care practitioner do not have
      better subsequent pain and disability outcomes than those who do not consult. Our
      findings raise questions about the current influence of medical care on the
      natural history of this condition.

PMID- 14719216
TI  - Comparing the self-reported referral and management preferences of pediatricians
      and family physicians for children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: The symptoms of juvenile rheumatoid arthritis (JRA) are often first
      recognized by primary care physicians. Little is known about the determinants of
      the initial management and referral patterns of these physicians for children
      with JRA. We compared the self-reported preferences and practices of
      pediatricians (PD) and family physicians (FP) in the diagnosis and management of
      children with JRA. METHODS: Surveys were mailed to a national random sample of
      700 PD and 867 FP. Questions included prior experience with JRA, usual patterns
      in the diagnosis and management of JRA, perception of the need for guidelines for
      referral and management of this condition, and physician demographic information.
      Data analysis included univariate and bivariate analysis. RESULTS: Response rates
      were 69% for PD and 49% for FP. Most respondents had seen very few JRA cases in
      the previous 5 years. Only 1% of respondents reported that they provided all
      diagnosis and management for patients with JRA. Forty-two percent of PD and 32%
      of FP refer all JRA diagnosis and management to subspecialists, while 46% of PD
      and 61% of FP refer only to confirm the diagnosis and guide initial therapy (p =
      0.011). More PD than FP (PD 92% vs FP 76%; p = 0.001) referred patients with JRA
      to pediatric rheumatologists, while more FP than PD referred to general
      rheumatologists (PD 17% vs FP 37%; p = 0.001). The majority of FP reported
      feeling more comfortable managing rheumatologic disease in adults than children
      (82%). Few respondents felt that they were up to date on the latest advances in
      JRA treatment (PD 10% vs FP 4%; p = 0.024). CONCLUSION: Multiple factors may
      contribute to physicians' referral practice, including a patient's clinical
      status and the physician's beliefs of inadequacy of training and inability to
      stay up to date. The pattern of care that children with JRA receive likely will
      be influenced by initial presentation to a PD or to a FP.

PMID- 14719217
TI  - Angiotensin converting enzyme gene insertion-deletion polymorphism is associated
      with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the incidence of angiotensin converting enzyme (ACE)
      gene insertion-deletion (I/D) polymorphism genotypes in children with juvenile
      rheumatoid arthritis (JRA), a heterogeneous chronic disease with autoimmune
      pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of
      ACE and has an involvement in inflammatory mechanisms. METHODS: The incidence of
      ACE gene I/D polymorphism genotypes was determined in 82 children with JRA from
      Kuwait and compared to that in 48 ethnically matched healthy controls using
      polymerase chain reaction. RESULTS: A considerably higher incidence of II
      genotype was observed in the JRA patients compared to controls (p < 0.003). In
      contrast, no statistically significant difference was detected in the incidence
      of DD and ID genotypes in JRA patients and controls (p = 0.276 and 0.460,
      respectively). The incidence of ACE gene polymorphism genotypes was also studied
      in clinical subclasses of JRA patients and controls. There was no significant
      difference in the incidence of DD and ID genotypes in either of the 3 JRA
      subclasses (oligoarticular, polyarticular, and systemic) when compared to
      controls. However, the incidence of II genotype was found to be significantly
      higher in all the 3 JRA subclasses compared to controls. The strongest
      association between II genotype and JRA subclasses was detected in systemic JRA,
      followed by oligoarticular and polyarticular JRA. This was also reflected in a
      higher prevalence of I-allele in the systemic JRA cases (13/26, 50%) compared to
      the D-allele (11/26, 42%). In contrast, D-allele of the ACE gene was more
      prevalent in oligoarticular and polyarticular JRA cases, than the I-allele (61%
      and 58%, respectively). CONCLUSION: Our data suggest a significant association of
      the I-allele of the ACE gene I/D polymorphism with the 3 clinical subclasses of
      JRA in children, and the highest association was observed in systemic JRA cases.

PMID- 14719219
TI  - Inflammatory arthritis secondary to metastatic gastric cancer.
AB  - Metastatic spread of malignancy to the joints is rare and only a few cases of
      solid tumors have been reported. We describe a patient with inflammatory
      arthritis of the knee and ankle secondary to metastatic gastric adenocarcinoma to
      the joints and bone diagnosed by synovianalysis. Arthritis secondary to
      metastatic cancer is a poor prognostic sign. The diagnosis is based on a strong
      clinical suspicion, magnetic resonance imaging, and joint fluid cytology or
      synovial biopsy.

PMID- 14719218
TI  - Microscopic polyangiitis associated with primary biliary cirrhosis.
AB  - We describe a patient with microscopic polyangiitis and primary biliary cirrhosis
      (PBC) who presented with a non-erosive polyarthritis followed by pulmonary and
      renal involvement and signs of liver disorder. Detection of pANCA and
      antimitochondrial antibodies with results of renal and liver biopsies allowed a
      diagnosis of microscopic polyangiitis and PBC. To our knowledge, this is the
      first report of an association between the 2 diseases.

PMID- 14719220
TI  - Severe relapsing polychondritis occurring after ear piercing.
AB  - We describe a case of relapsing polychondritis with laryngo-tracheal involvement,
      occurring after ear piercing in a 39-year-old woman. Polychondritis was clearly
      time-related to ear piercing. This association draws attention to the risk of
      relapsing polychondritis during body art practices with cartilage trauma.

PMID- 14719221
TI  - Intractable pain in a rheumatoid wrist.

PMID- 14719222
TI  - Rice bodies imaging in juvenile idiopathic arthritis.

PMID- 14719223
TI  - A case of edematous dermatomyositis.

PMID- 14719224
TI  - Linear scleroderma en coup de sabre and brain calcification: is there a
      pathogenic relationship?

PMID- 14719225
TI  - Tumor necrosis factor-alpha antagonists induce lupus-like syndrome in patients
      with scleroderma overlap/mixed connective tissue disease.

PMID- 14719226
TI  - Ocular inflammatory disease in patients with RA taking etanercept: is
      discontinuation of etanercept necessary?

PMID- 14719227
TI  - Effect of weather exposure on rheumatoid arthritis.

PMID- 14719228
TI  - Polymyalgia rheumatica and biopsy-proven giant cell arteritis exhibit different
      HLA-DRB1* associations.

PMID- 14719229
TI  - Biological and clinical markers of disease activity in ankylosing spondylitis.

PMID- 14719230
TI  - Ceiling effects and the Schober test.

PMID- 14719231
TI  - Fibromyalgia and pramipexole: promise and precaution.

PMID- 14719232
TI  - EMS responds to California wildfires.

PMID- 14719233
TI  - Intravenous montelukast in acute asthma.

PMID- 14719234
TI  - [A new life with MARS? The benefit of a new method still written in the stars].

PMID- 14719235
TI  - [Liver dialysis using MARS in acute hepatic failure. Promising results in a pilot
      setting].
AB  - Acute hepatic failure (AHF) is a life threatening condition with a high mortality
      rate. There is a need to buy time, either waiting for the liver to regenerate or
      waiting for urgent liver transplantation. Different modalities of "liver
      dialysis" have been used during the last decades but of no true success. However,
      a new technique has been developed called the MARS (Molecular Adsorbent Recycling
      System) built upon the same principle as haemodialysis but with the capacity to
      also remove albumin bound compounds thought to be toxic to the liver. This is a
      report of our ten first cases, all having AHF and considered for liver
      transplantation. The survival rate was 7/10 and of the 5 patients in need of 5 or
      more treatments all but one survived. In these cases the MARS-treatment seemed to
      have positive effects on the course and outcome of the disease but there are a
      need for controlled trials to clearly prove the benefit of the treatment.

PMID- 14719236
TI  - [New diagnostic approach can improve treatment of whiplash injuries. Functional
      magnetic resonance tomography makes visualization of the injuries possible].
AB  - Patients suffering from chronic pain and dysfunction after
      acceleration/deceleration trauma to the cervical spine often present reliability
      problems. This is partly due to inadequate possibilities of diagnosing of the
      soft tissue structures in this area. A new diagnostic method--functional magnetic
      resonance imaging (fMRI) has made it possible to detect injuries in ligaments and
      capsules at the craniocervical junction. Not only do these structures stabilize
      the head during rotation movements, but they also contain receptors of the
      central nervous system, and thus have the most important function in position
      perception (i.e. proprioception) and movement control. The late onset of symptoms
      in this patient group can now be explained by the functional stenosis of the
      spinal cord and brainstem due to scar formation around the dens axis after
      injury. Modern neurophysiology can now explain the background of the generalized
      and complex picture of chronic pain and muscular and cognitive dysfunction. This
      new knowledge has prepared the way for more specific therapy in patients
      suffering from craniocervical instability symptoms and pain from disks and facet
      joints in the cervical spine after whiplash trauma.

PMID- 14719237
TI  - [Management of asymptomatic primary hyperparathyroidism. New North American
      guidelines discussed from a Swedish perspective].
AB  - Primary hyperparathyroidism (HPT) is a common endocrine disease, in most cases
      without obvious symptoms of hypercalcemia and parathyroid hormone excess. The
      only curative treatment outside clinical trials is parathyroidectomy. Many
      patients are undiagnosed and left untreated, and the indications for curative
      treatment are still controversial. In 1990, NIH presented recommendations on the
      management of asymptomatic HPT, which was defined as HPT without symptoms and
      signs of renal or bone disease. Since then many studies have shed new light on
      mainly the cardiovascular complications and increased mortality of the disease,
      and the 1990 recommendations have been questioned. A workshop in 2002 revised the
      recommendations for handling of asymptomatic HPT in the United States. These
      recommendations are discussed from a Swedish perspective together with recent
      data on mortality in a large Swedish HPT cohort.

PMID- 14719238
TI  - [How are risk incidents in health care analysed and which information do patients
      receive?].
AB  - Deviations from the normal course of care occur in about one tenth of all
      hospitalizations. Investigation and analysis of an adverse incident should be
      systematic. The investigation should be conducted by a team within the
      organization. Material to be collected includes, aside from written reports,
      interviews of all involved parties. The investigation should not focus on
      individuals, but should concentrate primarily on organizational reasons for the
      incident. The affected patient (and his relatives) should always be informed as
      to what has happened, should be provided an explanation and, when appropriate, an
      apology. The patient must be provided an opportunity to describe the incident in
      his or her own words. Staff members involved in the incident often need
      professional psychosocial support. A climate of safety which would allow candid
      review and discussion concerning adverse incidents and errors must be engendered
      in health care. Awareness of legalities and the manner with which the Swedish
      system manages adverse incidents must be enhanced.

PMID- 14719239
TI  - [Drug therapy after stroke should be evidence-based. Organizational, economic and
      ethical decisions direct the choice of treatment].
AB  - Five types of drug therapy can be considered after stroke: antiplatelet therapy,
      anticoagulation with heparin or warfarin, blood-pressure-lowering therapy with
      ACE-inhibitors and diuretics, and finally cholesterol-lowering with statins.
      Aspirin therapy is the best-documented treatment to avoid another stroke, both in
      the acute and the long-term perspective. Warfarin treatment is fairly well
      documented for stroke patients with atrial fibrillation. Heparin therapy
      increases the risk for serious haemorrhage. Blood-pressure-lowering with a
      combined ACE-inhibitor and diuretic regimen has been shown to reduce the
      recurrence rate in younger patients with hemorrhagic as well as ischemic stroke.
      Statin therapy could be offered to younger stroke patients with a history of
      coronary heart disease. The increased occurrence of malignant diseases during
      statin therapy in elderly patients in one study deserves further investigations.

PMID- 14719240
TI  - [Children in Pakistan were followed up to the 12 years of age. Malnutrition,
      labor injuries and marriages between cousins are common causes of infant
      mortality, abnormalities and developmental disturbances].

PMID- 14719241
TI  - [Forensic psychiatry again in the melting-pot. Forensic psychiatrists criticize
      the new law proposal].

PMID- 14719242
TI  - [Oliver Sack's visit to Karolinska Institute. A phenomenal writer dedicated to
      the humanistic medicine].

PMID- 14719243
TI  - [The psychiatric reform is in need of reformation].

PMID- 14719244
TI  - [Crime and punishment in health care--proposals to reformation of the HSNA's
      handling].

PMID- 14719245
TI  - [Common sense against rolls of fat--should we reduce our intake of
      carbohydrates?].

PMID- 14719246
TI  - [Exodus of the big pharmaceutical companies from Sweden].

PMID- 14719247
TI  - [Frontal attack against family practitioners].

PMID- 14719248
TI  - [Computerized medical records test our honesty].

PMID- 14719249
TI  - [Dementia--don't forget the vitamins].

PMID- 14719250
TI  - [Occupational injury? Tips to those who issue sickness certificates].

PMID- 14719251
TI  - [Don't add iron!].

PMID- 14719252
TI  - [Kinetics and mechanism of removing Microcystis aeruginosa using clay
      flocculation].
AB  - Twenty-six natural clays were studied for their kinetics of flocculating and
      removing algal cells of Microcystis aeruginosa. According to the 8 h equilibrium
      removal efficiencies and removal rates at a clay-loading of 0.7 g.L-1, all the 26
      clays were classified into three categories. Type-I clay, which includes talc,
      ferric oxide, sepiolite, ferroferric oxide, and kaolinite, has an equilibrium
      removal efficiency greater than 90%, a t50 (time needed to remove 50% of the
      algae) of less than 30 min, and a t80 (time needed to remove 80% of the algae) of
      less than 2.5 h. Type-II clay, which includes argillanceous rocks, attapulgite,
      rectorite, illite, and argil, etc., has an equilibrium removal efficiency of 50%
      80%, a t50 of less than 2.5 h, and a t80 of more than 5 h. Type-III clay consists
      of 14 minerals, including laterite, zeolite, mica, clinoptilolite, pumice,
      tripoli, feldspar and quartz, etc. with the removal efficiency less than 50%, and
      t50 > > 8 h. When the clay loading was decreased to 0.1-0.2 g.L-1, the 8 h
      equilibrium removal efficiencies for 25 clays declined to below 60%, except for
      sepiolite, a Type-I clay, which maintained around 90%. After the sepiolite was
      modified with Fe3+ to increase its surface charge (Zeta potential from -24.0 mV
      to +0.43 mV at pH 7.4), the initial removal rate was increased remarkably
      although its 8 h equilibrium removal efficiency was not improved substantially.
      As a comparison, the 8 h equilibrium removal efficiency of PAC was no greater
      than 40% at loadings of 0.02-0.2 g.L-1. Following the analysis of the
      flocculation mechanism it was concluded that the effect of bridging and netting
      may play a key role in the clay-algae flocculation processes, which may be
      important for selecting and modifying clays to improve significantly the removal
      efficiency.

PMID- 14719253
TI  - [Microscopic characteristics and size distribution of summer PM10 in the air of a
      northwestern urban site and a clean air site in Beijing].
AB  - Microscopic characteristics and size distribution of individual particles in the
      summer (2001) PM10 collected at a northwestern urban site and a clean air site in
      Beijing have been investigated using high resolution Field Emission Scanning
      Electron Microscopy (FESEM) and image analysis technologies. The soot aggregates
      were observed at both sampling sites, showing a characteristic regional
      pollution. The irregular mineral particles existed commonly at the urban site but
      were rarely seen at the clean air site. The elongated gypsums and biological
      particles were observed only at the clean air site. PM10 displayed a biomodal
      number-size distribution, with a higher peak in 0.2-0.5 micron range and a lower
      peak in 1-2.5 microns range. In contrast, volume-size distribution of PM10
      exhibited a unimodal pattern with the peak in 1-2.5 microns range. The coarse
      particles, mainly minerals, had a considerable contribution to the PM10 mass,
      although they were insignificant in number. In PM2.5, however, the soot
      aggregates were dominant both in number and mass.

PMID- 14719254
TI  - [Impact of lead pollution in environment on children's health in Shenyang City].
AB  - In this thesis, based on field sampling and indoor integrated analysis with GIS
      technology, the impact of lead pollution in the atmosphere, dust, soil on the
      children was explored systemically. Results showed that, Lead exposure in
      environment was widely distributed and Lead pollution was serious in Shenyang
      city. The spatial variations of Lead, with four high content centers in the soil,
      dust and atmosphere, were distinct in all the environmental media. Moreover,
      there were daily, seasonal and annual variations in the atmosphere. The impact of
      lead pollution in environment on children health was serious in Shenyang city.
      The blood lead content of the children (ZPP > 2.3 mumol/L) with the age of 0-10
      ranged from 10.98 to 511.2 micrograms/L, and the average of 135.59 micrograms/L.
      The blood content of 40% children was beyond the normal standard. And correlative
      degree of lead contents between in blood and in atmosphere was highest, secondly
      in soil, and last in dust. With the implication of non-lead gasoline the lead
      content in the atmosphere had declined greatly. Along with the flying dust, the
      lead in the soil and dust was likely to entering into the atmosphere to bring out
      potential pollution risk.

PMID- 14719255
TI  - [Effects of solid adsorbents on the emission of heavy metals during coal
      combustion].
AB  - Experiments were carried out on laboratory-scale pulverized coal combustion with
      different adsorbents. Three solid adsorbents (calcium sulfate, limestone and
      bauxite) were used to control the emission of heavy metals (Pb, Cd, Cu, Co, Ni)
      during coal combustion. Sequential extraction procedure was developed for
      partitioning of metals species in coal ash into five fractions: absorbable
      metals, exchangeable metals, metals bound to carbonate, metals bound to sulfate,
      residual metals. The adsorbents showed a certain adsorptive ability to heavy
      metals, and different adsorbent had different ability. It can be proved from the
      distribution of heavy metals between coarse ash residues and fine particles and
      also from the increment of stable speciation of heavy metals in fine particles.
      Calcium sulfate was effective sorbent for removal of Pb, Cd and Cu, limestone for
      removal of Pb, Cd, Cu, Ni, and bauxite for removal of these five heavy metals.
      Fine adsorbents have higher adsorptive ability than coarse adsorbents.

PMID- 14719256
TI  - [Study on co-pyrolysis of coking-coal, plastic and dust].
AB  - The co-pyrolysis processes of different proportions of coking-coal, plastic,
      metallurgical dust (MD) were investigated using thermal analyzer (Setaram Labsys)
      under a neutral atmosphere of N2 at the sweep rate of 30 mL/min, the linear
      heating rate and the final pyrolysis temperature were 5 degrees C/min and 1000
      degrees C respectively in this study. The experimental results indicated that
      both the pyrolysis process of coking-coal and that of plastic were radical
      mechanism. In other word, within the relatively lower temperature range, a large
      amount of radicals were generated during their pyrolysis processes and stabilized
      through the intra-radical rearrangement reactions or inter-radical combination
      reactions. This means that sulfur containing in coal and plastic tends to formed
      gaseous sulfides, such as H2S, COS, CS2, etc. When co-existing with MD, these
      sulfides will react with metal oxides containing in MD to form metal sulfide with
      high stability and the cleaner coke oven gas (COG) were obtained. Within higher
      temperature interval of 500 degrees C-1000 degrees C, some of the gaseous
      products after pyrolysis (e.g. H2, CO and C) reinforce the reduction atmosphere
      that the coking reaction system needs and accelerate the reduction of metal
      oxides in MD and gasification of metal, which were conductive to the effective
      removal of sulfur in coke. Therefore, it is definitely feasible to adding waste
      plastic and MD into coking-coal to remove the sulfur in COG and coke
      simultaneously.

PMID- 14719257
TI  - [Separation of carbon dioxide from gas mixture by membrane contactor].
AB  - In this paper, membrane contactor made of hydrophobic hollow fiber polypropylene
      porous membrane (HFPPM) was used for separating carbon dioxide (CO2) from CO2/N2
      mixtures. The effects of absorbents, concentration and flow rate of feeding gas
      and absorbent solution, lumen/shell side processes and gas permeability of
      HFPPM(P) on the CO2 absorption efficiency were investigated. It was found that
      the absorption efficiency of three absorbents ranged in order of ethanolamine >
      sodium hydroxide > diethanol amine. For CO2/N2 mixture of c(in) = 20% and v(in) =
      0.5-1.0 m3.h-1, and MEA solution of cMEA = 2.5 mol.L-1 and vL = 40-160 L.h-1, the
      removal efficiencies of CO2 (eta) and the mass transport coefficients (K) was
      9.5% - 99.5% and 4.5-6.8 x 10(-4) m.s.-1 respectively. K of the modules made of
      HFPPM with larger P was relatively larger. eta in lumen process was 30% larger
      than that in shell process.

PMID- 14719258
TI  - [Structure and fluidization of an internally circulating fluidized bed for FGD
      process].
AB  - A new internally circulating fluidized bed for FGD process was developed, and
      different types of top and bottom structures were employed in the experiment to
      find out the best fluidized bed structure. Fluidizing status, the axial
      distribution of solid hold-up and the fluid mechanics under cold conditions were
      investigated. The results indicate that the unit can realize internally
      circulating of a large number of solid particles which presents an core-annulus
      structure when the velocity of fluidizing gas was at the range of 2.5 to 5 m/s,
      and that the solid density in the bed is higher than that in traditional equal
      diameter fluidized bed, which provide the equipment with potential for
      application in FGD process.

PMID- 14719259
TI  - [Technology of biodesulfurization from flue gases].
AB  - The desufurization in dilute sulfuric acid solution, acidic ferric solution, and
      microbial solution (Thiobacillus ferrooxidans) was studied in this paper. The
      concentration of ferric, pH value and time all affect the rate of
      desulfurization. The experimental results showed that in dilute sulfuric acid
      solution the absorption of SO2 was a physical absorption. In acidic ferric
      solution, the ion of ferric can not only catalyze but also oxidize SO2. The
      effects of desulfurization became obvious along with high concentration of ferric
      and pH value. Desulfurization rate was up to 90% when pH value was 2.0 and the
      concentration of ferric was 1.5 g/L. In microbial solution, the effects were also
      influenced by the concentration of ferric and pH value. Thiobacillus ferrooxidans
      had an ability of oxiding the ion of ferrous and S(IV). The results of
      desulfurization was the best at the concentration of ferric 1.5 g/L and pH 2.0.

PMID- 14719260
TI  - [The relationship between environmental change and stable carbon isotopes records
      from tree-ring in Mt. Helan].
AB  - The value of stable carbon isotope in plants is closely correlative with
      environmental factors. The stable carbon isotope chronology was attained from
      tree-ring alpha-cellulose in pine(Pinus tabulacformis), Mt. Helan. The relation
      between delta 13C series and precipitation from January to July was negatively
      correlative(r = -0.515, alpha = 0.05). And the delta 13C series was positive
      correlative with the average temperature from June to August(r = 0.427, alpha =
      0.05). Also the atmospheric CO2 content relates to the delta 13C series in the
      tree-ring cellulose. It was easy to find the increasing trend of CO2 composition
      in the atmosphere from the tree rings. By the relation between the number of
      sunspot and delta 13C series, the more number sunspot was correlated with higher
      delta 13C value was found.

PMID- 14719261
TI  - [Multimedia fate modeling with spatial resolution for phenanthrene in Tianjin].
AB  - Behavior and fate of phenanthrene in various phases in Tianjin were calculated
      using a multimedia model with spatial resolution under steady-state assumption.
      Spatial variation of two parameters, namely soil organic carbon content and
      emission from fossil fuel combustion, were taken into consideration. Both soil
      and air phases were further divided into 3113 sub-compartments and 6226 equations
      in total were solved simultaneously under mass-balance assumption. A number of
      output parameters, therefore, were generated and were used for mapping of
      phenanthrene concentrations in soil and air, as well as transfer fluxes between
      compartments. The model was evaluated in two ways. 1. Comparison between the
      calculated and the observed average concentrations in bulk compartments, and 2.
      Comparison of spatial distribution of the calculated and the observed
      phenanthrene concentrations in surface soil. In both cases, the predicted results
      are in fair agreement with the independently measured values. As the results of
      the modeling, it was demonstrated that soil and sediment, especially the later,
      is the primary sink of phenanthrene in the area over 70% of the chemical
      accumulated in sediment. The spatial distribution pattern of phenanthrene in
      surface soil depends on content of soil organic matter which prevent the
      degradation of the material by bacteria. For distribution in ambient air, the
      dominant controlling factor is the emission.

PMID- 14719262
TI  - [Arsenic adsorption by magnetic adsorbent CuFe2O4].
AB  - By the fact that Cu(II) and Fe(III) have strong affinity toward inorganic
      arsenic, the present paper reported the preparation of the magnetic adsorbent
      CuFe2O4 for the removal of arsenic. This adsorbent was composed with Cu(II) and
      Fe(III) oxides and can be recovered by magnetic separation technique. The
      characterization and the arsenic adsorption properties of the magnetic adsorbent
      were also studied. The sorption capacity was related to the pH of arsenic
      containing solution and the adsorption was more efficient for removing arsenic
      from acid and neutral solutions. As(V) was found to be more strongly adsorbed
      than As(III) on the adsorbent, and its adsorption capacity was 10 mg/g at
      equilibrium concentration of 10 micrograms/L (pH 3.5-6.5). Arsenic adsorption was
      not influenced by the presence of chloride and phosphate, but slightly influenced
      by sulfate at 10-20 times concentration of arsenic. As(V) desorption was
      performed more efficiently than As(III) desorption using 0.1 mol/L NaOH, which
      was the result of the different adsorption mechanism for the two arsenic species
      on adsorbent.

PMID- 14719263
TI  - [Effects of colloidal organic substrate on nitrification in biofilms].
AB  - The effects of colloidal and soluble organic substrates on nitrification in
      biofilms were investigated in biological aerated filters. The results showed that
      the hydrolysis process of colloidal organic matter took place rapidly, which
      could not be the limiting step of its oxidation in the biofilm. Some 70% organic
      matter oxidation was accomplished at the 40 cm at the bottom of the both filters,
      while the increase of organic matter in the influent resulted in the displacement
      of nitrification from the bottom to the upper part of filter bed. It was observed
      that the greater reduction on nitrification was caused by colloidal organic
      matter than by soluble organics at the same COD concentration.

PMID- 14719264
TI  - [Effect and mechanism of removal of nitrogen in the mimic sewage using bio
      zeolite system].
AB  - On the spot, the removal effect of pollutants such as NH3-N, N, NO3(-)-N, NO2-(
      )N, TN and COD in the mimic sewage by bio-zeolite system was studied. The
      following results were obtained: it was obvious and stable for the removal of NH3
      N by bio-zeolite with a removal efficiency over 95%, but the removal effect of
      NO3(-)-N was affected deeply by hydraulic retention time, according to the
      different removal mechanism; chemical adsorption and ion exchange were the main
      reasons for the removal of NH3-N as well as nitrification by microbe, while
      denitrification was the main reason for the removal of NO3(-)-N. Nitrification
      intensity of bio-zeolite was affected by the concentration of dissolved oxygen in
      the solution, so the nitrification intensity of bio-zeolite on the surface of the
      zeolite bed was two times of that in the middle in vertical direction.
      Denitrification intensity changed with different values of C/N in the study, and
      it could reach the maximum while COD/TN was 5; as for denitrification velocity,
      it was largest in the first six hour.

PMID- 14719265
TI  - [Improvement of biological pretreatment performance by addition of phosphorus].
AB  - Addition of phosphorus as a novel way to improve the performance of bio-ceramic
      filter for biological pretreatment of source water was conducted. More bacteria
      grown in raw water and the BDOC of raw water increased when 50 micrograms/L PO4(3
      )-P (NaH2PO4) was added alone were clear evidence of phosphorus limitation on
      bacterial growth. It shown that about 4.7%, 3.6% and 5.7% more of COD(Mn), UV254
      and TOC from the raw water investigated in the experiment on the average was
      removed respectively when 25 micrograms/L PO4(3-)-P (H3PO4) was added to the
      influent of bioceramic filter. The role of phosphorus in raw water and drinking
      water should be paid more attention.

PMID- 14719266
TI  - [Characteristics of aerobic biofilter backwash].
AB  - Periodic backwash is the vital stage to keep up the aerobic biofilter's
      performance. Under the same backwash conditions, a thorough study was done to
      review the influences on the performances of backwash in such aspects as backwash
      regimes, biofilter shapes. The experimental results show that the impulse
      backwash regime was superior to continuous backwash in the backwash performance
      and that the expansive flow aerobic biofilter was superior to the uniform flow
      aerobic biofilter in the performances of both backwash process and filter bed
      recovery. Then the optimal combination of the two factors i.e. the combination of
      impulse backwash mode and expansive flow filter was determined. Under the fixed
      filtration conditions, the appropriate impulse backwash parameters of expansive
      aerobic biofilter were determined as follows: the backwash air-flow intensity was
      8-10 L/(s.m2), the backwash water-flow intensity was 2-4 L/(s.m2), and the
      backwash duration was 5 min.

PMID- 14719267
TI  - [Rural sewage treatment performance of constructed wetlands with different
      depths].
AB  - The treatment performance, for low concentration rural sewage, through
      constructed wetlands of different depths(60 cm and 40 cm), was comparatively
      investigated by using pilot-scale apparatus in Lake Dian-chi area, Yunnan
      province, China. The experiment results showed, under a high hydraulic loading
      rate of 30 cm/d, that the removal efficiencies of COD, total nitrogen, ammonia
      nitrogen and total phosphorus in the constructed wetland of 60 cm depth were
      66.4%, 57.7%, 78.7% and 63.2%, respectively, and were 63.8%, 59.1%, 82.1% and
      61.3% in the 40 cm depth, respectively. The removal efficiencies of COD and total
      phosphorus in the constructed wetland of 60 cm depths were higher than those in
      the 40 cm depth, but the nitrogen removal efficiency in the latter was higher
      than that in the former. Nitrogen and phosphorus removal mechanisms were studied.
      The results showed that nitrogen removal through nitrification/denitrification
      and the phosphorus removal through absorb and sedimentation were their main
      removal mechanisms. The nitrogen and phosphorus removed by plant harvesting were
      amounting to 10% and 9% of input TN and TP, respectively, which was also an
      important removal pathway for nitrogen and phosphorus.

PMID- 14719268
TI  - [Performance and its influencing factors of a zeolite biofilter for dilute
      domestic wastewater treatment].
AB  - To reuse dilute domestic wastewater in power plant region as the makeup of
      recirculating cooling water, a renovate reactor--zeolite media biological aerated
      filter (ZBAF) was developed. A pilot scale ZBAF of 0.2 m in diameter and 3 m in
      media height was tested to treat dilute domestic wastewater. The results showed
      that turbidity, BOD5, CODcr and NH4(+)-N in effluent was 3.2 NTU, 3.2 mg/L, 14.5
      mg/L and 0.5 mg/L when the corresponding influent concentration was 59 NTU, 30
      mg/L, 81 mg/L and 16 mg/L, respectively, under the conditions of t = 12 degrees C
      17 degrees C, HRT = 1.4 h and gas/liquid = 4:1. The effluent quality met the
      water quality standards of the treated water reused for cooling water makeup. The
      removal rate of BOD5, COD and turbidity did not change much with the change of
      HRT and the ratio of gas to liquid, but NH4(+)-N removal rate changed greatly.
      The parameters along the depth of ZBAF showed that the biofilm phase was abundant
      in carbon-oxidation/nitrification(C/N) zone and simplex in nitrification (N)
      zone. Ciliate was plentiful in C/N zone. Biofilm in N zone was mainly consists of
      nitrifiers. The point that the number of ciliate decreased apparently was the
      boundary of the two zones.

PMID- 14719269
TI  - [Experimental study on the disinfection of wastewater by swept pulsed
      electromagnetic field].
AB  - In this paper, an applicable swept pulsed equipment was developed to treat the
      domestic wastewater and the effect of swept pulsed electromagnetic field on
      disinfection was studied. It was found that the effect was obvious and the
      disinfection performance of electromagnetic field was increased with the
      increasing of the pH, the temperature, the treatment time and the bactericidal
      concentration. The experimental results showed that the amounts of total
      bacterium and coliform per milliliter were decreased from 7.2 x 10(6) to 2.2 x
      10(4) and from 9.2 x 10(5) to 3.5 x 10(4) respectively after the treatment period
      of 4 h when the temperature was 25 degrees C and pH 9.0. Corresponding, the
      removal efficiency of total bacterium were 99.7% and 96.2%.

PMID- 14719270
TI  - [Kinetics of P-chlorophenol wastewater treatment by UV/H2O2 oxidation].
AB  - The photodegradation of p-cholorophenol in a hydrogen peroxide-aided photolysis
      process was investigated. The reaction was influenced by the original
      concentration of p-chlorophenol and H2O2 addition and carrier gas. With the aid
      of dioxygen, the removal of phenol and CODCr were reached about 96% and 50%
      respectively if the original concentration of H2O2 added was only half of
      stoichiometric calculation. A pseudo-first order kinetic model was adopted to
      represent the reaction.

PMID- 14719271
TI  - [Removal of phosphorus from aqueous solution by lanthanum hydrate].
AB  - Aiming at the development of novel efficient absorbents for phosphorus removal
      from wastewater, metal hydrates (MeH) were selected as adsorbent material.
      Several kinds of MeH were tested for phosphorus adsorption, and lanthanum hydrate
      (LaH) was found to possess a high adsorption capacity. Corresponding to solution
      pH change, LaH' s adsorption capacity changed largely, and at about pH = 3
      reached the peak. Its adsorption isotherm accorded prefer Langmuir's to
      Fruendrich's equations. Influences of different anions on its adsorption capacity
      were tested. This adsorbent was effective to adsorb orthophosphate but limited to
      remove polyphosphoric anion. The experimental results demonstrated that the LaH
      adsorbent was superior to traditional activated alumina adsorbent in adsorption
      performance.

PMID- 14719272
TI  - [Effects of sediment resuspension on nitrogen and phosphate exchange at the
      sediment-water interface in East Chongming Tidal Flat].
AB  - Sampling sediment and water to mimic sediment resuspension and researching its
      effects on nitrogen and phosphate exchange at the sediment-water interface in
      east Chongming tidal flat. Through the experiment, it was found that sediment
      resuspension causes NO3(-)-N, NH4(+)-N, NO2(-)-N and DIP releases. The release of
      NO3(-)-N is most marked, the increasing concentration of NO3(-)-N, NH4(+)-N, NO2(
      )-N and DIP reach in turns: 11.869 mumol.L-1, 2.1713 mumol.L-1, 0.2 mumol.L-1,
      0.02 mumol.L-1. At the same time, resuspension also change nitrogen and phosphate
      exchange at the sediment-water interface compare to without resuspension to great
      extent. NH4(+)-N and NO3(-)-N have absolutely opposite diversification with and
      without resuspension; NO2(-)-N shows complicated transformation because of many
      effected elements. The result of the experiment display the changes of NH4(+)-N,
      NO2(-)-N and DIP concentration in water have good relation to SPM (mg.L-1), this
      relation have not appear in change of NO3(-)-N.

PMID- 14719273
TI  - [Sorption characteristics of phenanthrene on sediments from Chinese southern
      rivers and lakes].
AB  - The sorption/desorption behavior of phenanthrene in five aquatic sediments from
      Chinese southern rivers and lakes were studied using multiple cycles of
      sorption/desorption experiments. The results showed that the sorption of
      phenanthrene on sediments was proportional to the content of organic carbon and
      that there were irreversible sorption processes. When the total sorption was
      separated into reversible and irreversible fractions, reversible sorption of
      phenanthrene on sediments could be better predicted by its partitioning between
      water and organic carbon phase. It was concluded that the sediment organic carbon
      could be the essential factor that controlling the environmental behavior of
      polycyclic aromatic hydrocarbon in aquatic sediment under study and the
      ecological risk should associated also with the irreversibility of the sorption
      processes.

PMID- 14719274
TI  - [Photolysis kinetics of propisochlor in water].
AB  - Propisochlor in water was irradiated at room temperature by a 400 W high pressure
      mercury lamp and sunlight, respectively. Influence of light and initiative
      concentration of propisochlor on the photolysis were studied. The results showed
      that under the irradiation of sunlight the photolysis fitted first order kinetics
      with only 5.5% degradation after one hour's irradiation in the quartz tube, that
      was a slow rate; while under the irradiation of high pressure mercury lamp the
      photolysis can be described by a double-chamber model, in which the degradation
      rate can reach 80.9% after 1 h. The higher the initiative concentration of
      propisochlor was, the slower the photolysis rate became, and the photolysis of
      propisochlor was influenced by the increasing photo-products. The six main
      photodegradation products were identified using GC-MS method. The aromatic ring
      was proved to be intact during the process. And the photolysis mechanism was then
      assumed on the basis of the photo-products detected.

PMID- 14719275
TI  - [Effect of surfactant on sorption of polar organic compounds in sediment].
AB  - Partition characters of phenol, aniline and p-nitrophenol in sediment-anionic
      surfactant sodium dodecylbenzene sulfonate(SDBS) system were researched. The
      results indicated that that the sediment-water partition coefficients K of
      aniline and p-nitrophenol increased when the initial concentrations were set at
      200 mg/L and 1200 mg/L for SDBS. The positive relation was found between
      partition enhancement and the KOW the of the organic compounds. But the K of
      phenol was different from that of aniline and p-nitrophenol in SDBS system with
      initial concentration set for 1200 mg/L and it was lower than that in pure water.
      The data showed that in sodium dodecyl sulfate (SDS), Triton X-100 (TX100) and
      Brij30 systems respectively, the sorption of phenol on the sediment was enhanced
      by surfactants below their critical micelle concentration(CMCs), but it was
      diminished above the surfactant CMCs.

PMID- 14719276
TI  - [Effects of long-term exposure of low-level 2,4-dichlorophenol on the antioxidant
      defense system in liver of Carassius auratus].
AB  - Under the indoors simulant conditions, the effects of long-term exposure of low
      level 2,4-Dichlorophenol on the antioxidant system of larval fishes were studied.
      The results showed that the activities of catalase (CAT), sedium-dependent
      glutathione peroxidase (Se-GPx) and the content of oxidized glutathione (GSSG)
      were induced significantly. The activity of superoxide dismutase (SOD) was
      induced remarkably when 2,4-Dichlorophenol level was at only 0.005 mg.L-1; the
      content of reduce glutathione (GSH) was almost suppressed continuously; the
      activity of glutathione reductase was inhibited firstly and then restored
      gradually; the activity of glutathione S-transferase (GST) had slight variances
      among groups. GR, GSH, especially SOD, can act as an early monitoring index of
      2,4-Dichlorophenol pollution in aquatic ecosystem.

PMID- 14719277
TI  - [Effect of lignosulfonates on controlling of urea nitrogen transformation and
      nitrate accumulation in vegetable].
AB  - Indoor cultivation experiment and plot field experiment were conducted to study
      the effect of lignosulfonates on urea nitrogen transformation in soil and the
      mechanism of controlling nitrate pollution in vegetable. Results showed that
      lignosulfonates behaved inhibition effect on urea hydrolysis compared with the
      contrast treatment, the contents of remainder urea nitrogen treated with
      lignosulfonates was more than that of another kind of urease inhibitor
      hydroquinone in soil after 69 hours' cultivation. Lignosulfonates could reduce
      contents of nitrate in cabbage, it as well increase contents of vitamin C in a
      large degree, enhance the nitrate reductase activity, then accelerated nitrogen
      assimilation in plants. The urease activity was lower and contents of ammonium
      nitrogen in soil was larger after ingathering, lignosulfonates could keep
      nitrogen release slowly, and could be used as a kind of effective inhibitor to
      nitrogen fertilizer in the controlled-release fertilizers.

PMID- 14719278
TI  - [Co-composting of high-moisture vegetable waste and flower waste in a batch
      operation].
AB  - Co-composting of different mixture made of vegetable waste and flower waste were
      studied. The first stage of composting was aerobic static bed based temperature
      feedback in a batch operation and control via aeration rate regulation. The
      second stage was window composting. The total composting period was 45 days.
      About the station of half of celery and half of carnation, the pile was insulated
      and temperatures of at least 55 degrees C were maintained for about 11 days. The
      highest temperature was up to 65 degrees C. This is enough to kill pathogens.
      Moisture of pile decreased from 64.2% to 46.3% and organic matter was degraded
      from 74.7% to 55.6% during composting. The value of pH was had stable at 7.
      Analysis of maturity and nutrition of compost show that end-products of
      composting were bio-stable and had abundant nutrition. This shows that co
      composting of vegetable waste and flower waste can get high quality compost by
      optimizing composting process during 45 days. Composting can decrease non-point
      resource of organic solid waste by recycling nutrition to soil and improve
      fertility of soil.

PMID- 14719279
TI  - [PRB technology in situ remediation of groundwater polluted by landfill
      leachate].
AB  - In this paper three reaction media zero valent iron (ZVI), a mixture of ZVI and
      activated carbon, a mixture of the ZVI and zeolites were used to design three
      kinds of permeable reactive barrier (PRB), viz. reactors A, B and C and to study
      the feasibility and the efficiency of the PRB technology in the remediation of
      leachate-polluted groundwater. The designs of the reactors took into account the
      relation of the permeability of the reactor with the permeability of the aquifer.
      The results indicated that the COD removal ratios of the reactor A, B and C were
      more than 80%, 90% and 70% respectively and the value of the BOD5/COD increased
      from 0.32 up to 0.781, 0.728, 0.716 respectively. Total nitrogen decreased from
      50 mg/L to less than 10 mg/L and the removal ratio of the ammonium ranged from
      78%-91%. Zeolites of the reactor C manifested effectiveness in the removal of
      heavy metals and hardness. The removal ratios of Mn ion, Zn ion and hardness were
      up to 90%, 80%, 81% respectively. These results indicate that PRB technology is
      an efficient method for the treatment of leachate-contaminated groundwater.

PMID- 14719280
TI  - [Effects of railway noise on residential quarter].
AB  - Effects of direct sound and one time reflection of railway noise on residential
      quarter were mainly considered, and model for prediction of attenuation of
      railway noise in residential quarter was given in the paper. With the given
      model, the effects of railway noise on residential quarter were analyzed and
      compared with measure results, it was shown that the model is suitable for
      prediction to attenuation of railway noise in residential quarter.

PMID- 14719281
TI  - ED is hotbed for lawsuits; take simple steps to address riskiest conditions.

PMID- 14719282
TI  - Take tip from restaurants to ease waits, ED advises.

PMID- 14719283
TI  - Flu season severe: FluMist may pose little risk.

PMID- 14719284
TI  - Cross-training your staff necessitates caution.

PMID- 14719285
TI  - Is it OK to have someone very quickly screen incoming patients?

PMID- 14719286
TI  - Tongqiao huoxue tang and buyang huanwu tang for treatment of vascular dementia--a
      report of 36 cases.

PMID- 14719287
TI  - Clinical observation in 31 cases of chronic bronchitis at remission stage treated
      with bufei keli.
AB  - To observe the therapeutic effects of a Chinese drug Bufei Keli ([symbol: see
      text] granules for invigorating the lung) in the treatment of chronic bronchitis
      at remission stage, 62 cases were randomly divided into a treatment group
      (treated with Bufei Keli) and a control group (treated with Yupingfeng Keli
      [symbol: see text]). The results turned out to be that the short-term clinically
      controlled and markedly effective rate was 77.42% and the long-term relapse
      resisting markedly effective rate was 74.2% in the treatment group, which were
      obviously higher than 45.16% and 38.71% respectively in the control group (P <
      0.05). And the increase in contents of SOD and CD3 and the decrease in LPO
      content in the treatment group were also bigger than that in the control group (P
      < 0.01). It is therefore concluded that Bufei Keli can improve qi deficiency
      syndrome and raise the immunity of patients with chronic bronchitis, hence its
      effect of resisting relapse of chronic bronchitis.

PMID- 14719288
TI  - Effects of da ding feng zhu decoction in 30 cases of liver fibrosis.
AB  - To study the clinical effects of Da Ding Feng Zhu ([symbol: see text]) Decoction
      on liver fibrosis. 56 patients with liver fibrosis due to chronic hepatitis B
      were randomly divided into a treatment group (30 cases treated with Da Ding Feng
      Zhu Decoction) and a control group (26 cases treated with colchicine). The serum
      levels of hyaluronic acid (HA), procollagen III (PC-III), IV collagen (IV-C) and
      Laminin (LN) of the patients were determined, compared and analyzed before
      treatment and after 3-month treatment in the two groups. The results showed that
      in the treatment group, the levels of HA, PC-III, IV-C and LN after 3-month
      treatment were significantly lowered as compared to that before treatment (P <
      0.01). In the control group, only the HA level was obviously lowered (P < 0.05).
      There was an significant difference (P < 0.05) in PC-III and IV-C and a very
      significant difference (P < 0.01) in HA after treatment between the two groups.
      It is therefore concluded that Da Ding Feng Zhu Decoction can lower serum indexes
      of liver fibrosis.

PMID- 14719289
TI  - Clinical observation in 86 cases of acne vulgaris treated with Compound
      Oldenlandis Mixture.
AB  - 86 cases of acne vulgaris were treated with Fu Fang She She Cao He Ji ([symbol:
      see text] Compound Oldenlandis Mixture), with the other 34 cases treated with
      Dang Gui Ku Shen Wan ([symbol: see text] Pills Prepared from Chinese Angelica and
      Flavescent Sophora Root) as the controls, to observe the therapeutic effect of
      the former. The results showed that the cure plus markedly effective rate was
      73.26% in the treatment group, and 47.06% in the control group, with a
      significant difference in the cure plus markedly effective rate between the two
      groups (P < 0.01), and also in the total effective rate between the two groups
      significant (P < 0.05). It may be concluded that the Compound Oldenlandis Mixture
      is a better agent for the illness.

PMID- 14719290
TI  - Clinical application of insect drugs.

PMID- 14719291
TI  - Jiedu tongbi tang plus phenytoin sodium for severe acute sciatica.

PMID- 14719292
TI  - Prof. Zhou Xuewen's experience in treating superior mesenteric artery syndrome.

PMID- 14719293
TI  - Application of the drugs for expelling the pathogenic wind in treatment of
      chronic diarrhea.

PMID- 14719294
TI  - Effects of huo nao fang in 60 cases of ischemic apoplexy.
AB  - To observe the therapeutic effects of the prescription of Huo Nao Fang ([symbol:
      see text]) on ischemic apoplexy, 120 patients were divided into a treatment group
      and a control group, with 60 in each group, the former treated with Huo Nao Fang
      while the latter with western medicine. The nervous function and blood rheology
      were tested before and after treatment for both groups, and the effects of Huo
      Nao Fang were evaluated. The results showed that the total effective rate was
      91.7% in the treatment group and 61.6% in the control group, with a significant
      difference (P < 0.01) between the two groups. The treatment group was superior to
      the control group in improving blood rheology, reducing blood lipid and restoring
      the nervous function (P < 0.05).

PMID- 14719295
TI  - Clinical study on therapeutic effect of acupuncture on Behcet's disease.
AB  - Forty-six cases of Behcet's disease were randomly divided into two groups. The 26
      cases in the treatment group were treated by acupuncture and the 20 cases in the
      control group with the drugs. The level of L-chain (kappa) of IgM and the level
      of the trace element Zn were determined before and after treatment in the
      treatment group. The results showed that the recurrence rate in the treatment
      group was significantly lower than that in the control group (P < 0.01), and the
      differences in the level of L-chain (kappa) of IgM and level of Zn in the
      treatment group before and after treatment were very significant (P < 0.01).
      These two indexes tended to become normal after treatment.

PMID- 14719296
TI  - Electro-acupuncture for treatment of dysequillibrium due to cerebellum or brain
      stem infarction.

PMID- 14719297
TI  - Clinical application of the point xuanzhong.

PMID- 14719298
TI  - Acupuncture treatment of chronic superficial gastritis by the eight methods of
      intelligent turtle.
AB  - With the clinical manifestations and the point electric conduction volume as the
      indexes, the authors observed the immediate effects of the acupuncture treatment
      on chronic superficial gastritis with the points selected according to the date
      and time set by Ling Gui Ba Fa ([symbol: see text] Eight Methods of Intelligent
      Turtle), which was compared with the effects in the control group treated with
      the points selected according to syndrome-differentiation. A higher symptom
      improvement rate (P < 0.01) and a higher channel's balance-inverting rate were
      noticed in the former (P < 0.01), indicating that Ling Gui Ba Fa can give a
      better therapeutic results.

PMID- 14719299
TI  - Juvenile myasthenia laryngis treated by acupuncture and TCM medication.

PMID- 14719300
TI  - The therapeutic effects of triple puncture and routine body needling for cervical
      spondylosis.

PMID- 14719302
TI  - Clinical observation on acupuncture treatment of ischemic apoplexy by nourishing
      the kidney and regulating the du channel.

PMID- 14719301
TI  - Electric acupuncture in the treatment of 36 cases of female urethral syndrome.

PMID- 14719303
TI  - Effects of magnetic needle acupuncture on blood pressure and plasma ET-1 level in
      the patient of hypertension.

PMID- 14719304
TI  - Experimental study on cheng zai wan for treatment of necrosis of the femoral
      head.
AB  - Cheng Zai Wan ([symbol: see text]), a Chinese herbal preparation was
      administrated in the two-leg rat model of aseptic necrosis of the femoral head
      established by taking prednisone acetate for a long period and the osteoporosis
      model rat by castration in order to explore the effects of the prescription on
      necrosis of the femoral head. The results showed that after treatment, the
      pitting on the surface of the femoral head disappeared, the reticular structure
      with filling cells was restored; the fat droplets in bone cells or cartilage
      cells of the femoral head were significantly reduced; sparse capillaries were
      improved, density and width of the bone trabecula were increased somewhat; bone
      mineral density, bone weight, bone strength and rigidity were significantly
      increased; and the low level of estrin was improved. It is suggested that Cheng
      Zai Wan has definite therapeutic effects on aseptic necrosis of the femoral head.

PMID- 14719305
TI  - The recent studies on treatment of the damaged intestinal mucosa.

PMID- 14719306
TI  - How to different and treat irritable bowel syndrome with Chinese drugs?

PMID- 14719307
TI  - How to treat restless leg syndrome with traditional Chinese medicine?

PMID- 14719308
TI  - The model of traditional Chinese medicine.
AB  - Medical model, which guides medical practice, belongs to the field of philosophy.
      It is retrospective cognition in medicine abroad and changes with the conditions
      of medical practice. The biological medical model came out in the 15th century.
      Since then, it has made a great deal of contributions to the development of
      medicine. In the late years of the 19th century, biological medical model showed
      inadequate in some aspects. It was not replaced by biopsychosocial medical model
      until the 20th century. The model of traditional Chinese medicine is prospective.
      Its formula is Time--Space--Social--Psychological--Biological, which includes
      more elements than the model of modern medicine, guiding the practice and
      development of traditional Chinese medicine for more than two thousand years.

PMID- 14719309
TI  - [Screening of HIV in blood banks. Evaluation of fourth generation kits].
AB  - Use of detection tests for p24 HIV antigen (p24Ag) in blood banks in Argentina is
      recommended by the Argentinean Society of Hemotherapy and Immunohematology. In
      the blood bank of the National University of Cordoba (Argentina), the recent
      implementation of the p24Ag screening test has considerably increased the cost of
      the battery of screening tests and its use in all blood donations has not
      produced the benefits expected. A 4th generation EIA was evaluated for the
      screening of HIV in comparison with the currently used assays in the blood bank
      of National University of Cordoba (3rd generation EIA + p24Ag assay). For this
      comparison, 11 serum samples from subjects with early HIV infection (early
      seroconversion period) were tested, as well as 27 serum samples from asymptomatic
      HIV-infected subjects and other 39 from non-HIV infected subjects. The 3rd
      generation EIA and the 4th generation EIA showed the same sensitivity value
      (100%) but the specificity of the 3rd generation EIA was higher (97.5%) comparing
      with 4th generation (95.1%). Besides, the p24Ag test failed to detect 2 samples
      from subjects with early HIV infection. These results indicate a good performance
      of both 3rd and 4th generation assays for screening of HIV. However, due to the
      lowest cost of 4th generation EIA kit, it could replace the currently used assays
      for HIV screening in regional blood banks. This screening assay will lead to gain
      in effectiveness and reduced costs until the detection of HIV RNA can be
      implemented in blood banks.

PMID- 14719310
TI  - [Assessment of diastolic function in Chagas disease with pulsed Doppler tissue
      imaging].
AB  - Diastolic function is early involved during the undetermined form of Chagas
      disease. Pulsed Doppler tissue imaging is a new technique to evaluate diastolic
      function by mean of the record of myocardial velocities in the longitudinal axis.
      With the purpose to evaluate diastolic function by pulsed Doppler tissue imaging
      in patients with Chagas disease, we studied with Doppler echocardiography 51
      patients (age average 48 +/- 12 years) and 24 normal subjects (age average 47 +/-
      15 years) as a control group. Patients were divided in two groups according to
      the pattern of mitral and pulmonary vein flow: restrictive (17 patients) and no
      restrictive (35 patients). Peak velocity of E wave of the lateral mitral annulus
      was diminished in no restrictive and restrictive patients (0.13 +/- 0.04 m/s,
      0.11 +/- 0.05 m/s respectively) in regard to control group (0.18 +/- 0.07 m/s, p
      < 0.01). Pulsed Doppler tissue imaging was useful in the assessment of diastolic
      function in Chagas disease, including patients with no restrictive mitral and
      pulmonary vein filling pattern.

PMID- 14719311
TI  - Attributable risks for acute myocardial infarction in four countries of Latin
      America.
AB  - This multicenter case control study investigated, in four countries of America,
      the proportions of acute myocardial infarction (AMI) attributable to cholesterol,
      smoking, hypertension, body mass index, diabetes and family history of coronary
      heart disease (attributable risks, AR). AR were estimated using information from
      1060 cases of AMI and 1071 controls from Argentina, 323 cases of AMI and 314
      controls from Cuba, 200 cases of AMI and 200 controls from Mexico and 266 cases
      of AMI and 264 controls from Venezuela. AR were obtained from the prevalence of
      coronary risk factors in the cases and the corresponding Odds Ratio (OR) derived
      through appropriate multivariate models. The AR for AMI observed for
      hypercholesterolaemia were the following: Venezuela 27%, Mexico 3%, Cuba 30% and
      Argentina 36%; for diabetes: Venezuela 10%, Mexico 15%, Cuba 5% and Argentina 7%
      and for body mass Index: Venezuela 12%, Mexico 3%, Cuba 19% and Argentina 17%.
      The same risk factor may have a different attributable risk in different
      populations. Together, hypercholesterolaemia, hypertension, smoking, diabetes,
      body mass index and family history of coronary heart disease accounted for 76% of
      all cases of AMI in Venezuela, 70% in Mexico, 81% in Cuba and 79% in Argentina.
      The knowledge of attributable risks could have important implications for public
      health strategies, especially in those countries with limited health care
      resources.

PMID- 14719312
TI  - [Leptin in patients with polycystic ovary syndrome. Direct correlation with
      insulin resistance].
AB  - Up to now it is unclear whether there is a relationship between insulin
      resistance and circulating leptin levels (LEP) in women with polycystic ovary
      syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the
      relationship between plasma LEP levels and insulin resistance (IR) in PCOS
      patients, we studied 49 women with PCOS and 14 normal premenopausal women. All
      subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting
      plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index
      (BMI) were determined. Results were analyzed by ANOVA and the Pearson's
      correlation test when appropriate. The results indicate that: 1) no differences
      were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and
      PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01)
      correlation between plasma LEP levels and BMI and insulin sensitivity indexes
      were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed
      higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/-
      0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2
      and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be
      associated with normoleptinemia, however, if IR are analyzed separately from non
      IR PCOS patients, there is a clear relationship between IR PCOS and
      hyperleptinemia, regardless of the BMI. The present study strongly supports bi
      directional relationship between fat and carbohydrate metabolisms under a very
      particular physiopathological condition (PCOS).

PMID- 14719313
TI  - [Echocardiographic detection of heart valvular disease in cocaine addict
      patients].
AB  - Intravenous drug-addiction is one of the susceptible factors for the development
      of infectious endocarditis and cocaine, especially when administered
      intravenously, can produce damage at the level of the valvular endothelium. We
      have studied a group of cocaine addicts to evaluate the possible existence of
      valvular alterations. Ninety-eight patients, addicts to intravenous injection
      and/or nasal insufflation, have been studied with Doppler and echocardiography
      and they were compared with a non-addict group of fifty persons. Valvular lesions
      were defined as valvular enlarging and "beaded appearance" lesions. The average
      age of drug-addicts was 29.1 years (SD 8.31) with a maximum of 66 year and a
      minimum of 14 years. Ninety-three of them were males and forty-five of them
      admitted to be intravenous addicts. Twenty cases showed positive serology for
      HIV. All of them, except one, recognized having used the intravenous route. The
      control group was 27.78 years old (SD 3.49) and 96% were males. Valvular lesions
      were found in 22.45% of addicts while no one in the control group showed any
      lesion (p = 0.0007). Lesions were significantly larger in the tricuspid valve (p
      = 0.0004). No valvular dysfunction was detected in any of the studied cases. No
      differences have been noticed in valvular alterations among HIV infected patients
      with and without reactivity to the treatment. The prevalence of valvular
      affection considering the way of drug administration was significantly higher in
      patients with intravenous addiction compared to nasal insufflation addicts, 40%
      versus 7.5% (p = 0.0001). A percentage of cocaine addicts here studied presented
      valvular alterations research being the tricuspid valve the most frequently
      involved. No significant valvular failure has been detected. The observed lesions
      could correspond to the anatomic substratum of an endocardiac infection,
      frequently observed in intravenous drug-addicts with lesions, usually located in
      the tricuspid valve.

PMID- 14719314
TI  - [Effect of alcohol-gel hand hygiene on nosocomial infections due to multi
      resistant Klebsiella pneumoniae].
AB  - Handwashing is considered the most important and effective infection control
      measure to prevent transmission of nosocomial pathogens. However, compliance with
      handwashing by health care workers is low. A new modality for hand hygiene is
      alcohol gel rub, which reduces time required, does not damage the skin and
      increases health care workers compliance. An observational study was conducted to
      assess the effect of alcohol-gel hand antiseptic on infection rates due to the 3
      more frequent multi-resistant bacteria (Staphylococcus aureus, Klebsiella
      pneumoniae y Pseudomonas aeruginosa) in our hospital. Two periods were compared,
      12 months before and 12 months after starting alcohol gel use. The second period
      (AG use) showed a significant reduction on incidence rates of Klebsiella
      pneumoniae with extended spectrum betalactamase (RR: 0.38) overall infections and
      specially bacteremias (RR: 0.10). Nevertheless, on the basis of this study, we
      cannot conclude that the result was due to AG itself or to an increase in hand
      hygiene compliance.

PMID- 14719315
TI  - [Subcutaneous emphysema of hand and forearm due to high-pressure injection of
      air].
AB  - Cutaneous injuries with crepitus suggest infections caused by gas forming
      organisms. The non infectious causes of subcutaneous emphysema are under
      recognized, and are usually of good prognosis. A 27 year old man presented a
      swollen hand and forearm. He had suffered a small puncture wound in a finger. He
      had cleaned and dried the area briefly with compressed air, developing a fast
      swelling of this hand and forearm. At examination, we found extended subcutaneous
      emphysema in a radiography and observed subcutaneous air in the hand and forearm;
      48 hs later there was no evidence of subcutaneous air. The presence of
      subcutaneous emphysema is always worrisome and such cases must be considered in
      the differential diagnosis. The exposition of preexistent wounds to compressed
      air sources (high pressure pneumatic tools, scuba compressed air tubes,
      compressed air guns) identifies the cause and prevents unnecessary surgical
      interventions.

PMID- 14719316
TI  - [Masquerade syndrome in a patient with a primary central nervous syndrome
      lymphoma].
AB  - We report the case of a 37-year-old, white male with a primary central nervous
      system lymphoma with multiple supra and infratentorial locations. The patient
      developed manifestations of intraocular inflammation secondary to the
      intracranial neoplasm (masquerade syndrome) and lymphocytopenia--with a low CD4
      cell count--representing an immunodeficiency state which etiology was
      undiagnosed. The diagnosis of lymphoma was established by vitreous cytology. The
      patient died 10 months after the beginning of the symptoms.

PMID- 14719317
TI  - [Severe pericardial effusion and systemic lupus erythematosus].

PMID- 14719318
TI  - [Chronic renal insufficiency and growth].
AB  - Many children with chronic renal insufficiency (CRI) show growth retardation. Our
      objective is to describe the natural history of growth in patients with CRI, its
      pathogenesis and its optimization. Final height remains below percentile 3 in 77%
      of male and 71% of female patients. The etiology of growth retardation in these
      children is multifactorial age at onset, primary renal disease, fluid and
      electrolyte abnormalities especially acidosis, renal osteodystrophy, inadequate
      caloric intake and perturbations of growth factors are all implicated. Post Tx,
      immunosuppressive corticoid therapy and reduced glomerular filtration rate have a
      significantly negative effect on final height. Growth retardation in both CRI and
      renal Tx patients is not the result of abnormal growth hormone secretion or
      decreased levels of IGF-I, but rather of elevated levels of IGF-I binding
      proteins inhibiting the bioavailability of the IGFs. Optimization of growth
      includes reduced corticoid dose, alternate-day instead of daily prednisone
      therapy, or substituting deflazacort for methylprednisone. Several studies have
      shown that growth hormone (GH) therapy at a dose of 30 UI/m2/week results in
      growth improvement and this led the Food and Drug Administration to approve the
      use of GH prior to Tx. The response to GH is better during conservative therapy,
      less in allograft recipients and substantially less while undergoing dialysis. In
      conclusion, in those children with short stature, GH treatment should begin at an
      early age and during conservative therapy, trying to shorten dialysis in order to
      attain better height at the time of renal transplantation.

PMID- 14719319
TI  - [Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of
      osteoporoses].
AB  - The current (metabolic) conception of bone-weakening diseases regards bone
      strength as determined by a systemically-controlled "mineralized mass" which
      grows until it reaches a peak and then is lost at individually-specific rates.
      This concept disregards bone biomechanics. Skeletons are structures, it reaches
      of which depends on the stiffness and the spatial distribution rather than the
      volume of the calcified material. Rather than allowing a systemic regulation of
      their "mass" as a way to optimize their strength, bones autocontrol their
      stiffness by orienting bone formation and destruction as locally determined by
      the directional sensing, by osteocytes, of the strains caused by mechanical usage
      (gravity, muscle contractions). Bone mass and strength are just side products of
      that control. Endocrine-metabolic systems modulate non-directionally the work of
      bone cells as required for achieving a mineral equilibrium, despite the
      biomechanical controls, and can determine osteopenias and osteoporoses.
      Osteoporoses are not "intense osteopenias" (as per the current WHO's conception)
      but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis
      of osteopenia is an anthropometric problem that can be solved densitometrically;
      but that of bone fragility is a biomechanical matter that requires evaluation of
      bone material's stiffness and distribution by other means ("resistometry"). For
      therapeutic purposes, osteopenias and osteoporoses should be also evaluated
      according to the relationship between bone mass or strength and muscle mass or
      strength in order to distinguish between "mechanical" (disuse) and "metabolic"
      etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the
      bone/muscle proportionality tends to remain normal or to deteriorate,
      respectively.

PMID- 14719320
TI  - [Medical use of cannabis and synthetic cannabinoids].

PMID- 14719321
TI  - [Robert Hooke (1635-1703)].

PMID- 14719322
TI  - [Neoplasms etiology. Validity of 5 successive paradigms].

PMID- 14719323
TI  - [Vaccine production in Argentina: a decision that cannot be postponed].

PMID- 14719324
TI  - Microscope basics.

PMID- 14719325
TI  - The optics of microscope image formation.

PMID- 14719326
TI  - Proper alignment of the microscope.

PMID- 14719327
TI  - Mating cameras to microscopes.

PMID- 14719328
TI  - "Do not (mis-)adjust your set": maintaining specimen detail in the video
      microscope.

PMID- 14719329
TI  - Cameras for digital microscopy.

PMID- 14719330
TI  - Electronic cameras for low-light microscopy.

PMID- 14719331
TI  - Cooled vs. intensified vs. electron bombardment CCD cameras--applications and
      relative advantages.

PMID- 14719332
TI  - Fundamentals of fluorescence and fluorescence microscopy.

PMID- 14719333
TI  - A high-resolution multimode digital microscope system.

PMID- 14719334
TI  - Fundamentals of image processing in light microscopy.

PMID- 14719335
TI  - Techniques for optimizing microscopy and analysis through digital image
      processing.

PMID- 14719336
TI  - The use and manipulation of digital image files in light microscopy.

PMID- 14719337
TI  - High-resolution video-enhanced differential interference contrast light
      microscopy.

PMID- 14719338
TI  - Quantitative digital and video microscopy.
AB  - Obviously there are many variations and embellishments on the topic of
      quantitating your image. I have tried here to offer you a very practical guide
      that highlights some of the critical issues, paying particular attention to
      problems that can prevent or compromise your success. These include errors caused
      by aspect ratio, use of automatic camera settings, improper setting of dynamic
      range, and use of integer arithmetic. Further information can be found in several
      other chapters in this volume as well as in the references provided. In addition,
      you should not overlook the technical manuals that come with your imaging
      systems. The field of digital microscopy has evolved as a cooperative effort
      between academia and industry. As a result you will find that many of the
      technical support personnel from microscope, camera, and image-processing
      companies are well versed on the issue of digital imaging in biology and are more
      than willing to assist you.

PMID- 14719339
TI  - Computational restoration of fluorescence images: noise reduction, deconvolution,
      and pattern recognition.

PMID- 14719340
TI  - Quantitative fluorescence microscopy and image deconvolution.

PMID- 14719341
TI  - Ratio imaging: measuring intracellular Ca++ and pH in living cells.

PMID- 14719342
TI  - Ratio imaging instrumentation.
AB  - Using ratio imaging to obtain quantitative information from microscope images is
      a powerful tool that has been used successfully in numerous studies. Although
      ratio imaging reduces the effects of many parameters that can interfere with
      accurate measurements, it is not a panacea. In designing a ratio imaging
      experiment, all of the potential problems discussed in this chapter must be
      considered. Undoubtedly, other problems that were not discussed can also
      interfere with accurate and meaningful measurements. Many of the problems
      discussed here were observed in the authors' laboratories. In our experience
      there are no standard routines or methods that can foresee every problem before
      it has been encountered. Good experimental design can minimize problems, but the
      investigator must continue to be alert. Progress in instrumentation continues to
      overcome some of the difficulties encountered in ratio imaging. CCD cameras with
      12- to 14-bit pixel depth are being used more frequently, and several confocal
      microscope manufacturers are now also using 12-bit digitization. The dramatic
      increase in the use of confocal microscopes over the past decade is now causing
      microscope manufacturers to more critically evaluate the effect of axial
      chromatic aberration in objectives, and recent designs to minimize this problem
      are being implemented. Other developments such as the use of AOTFs to attenuate
      laser lines extend the applicability of ratio imaging. Ratio imaging is clearly
      applicable to a wide range of cell biological problems beyond its widespread use
      for measuring ion concentrations. Imaginative but careful use of this technique
      should continue to provide novel insights into the properties of cells.

PMID- 14719343
TI  - Fluorescence resonance energy transfer microscopy: theory and instrumentation.

PMID- 14719344
TI  - Fluorescence-lifetime imaging techniques for microscopy.

PMID- 14719345
TI  - Fluorescence correlation spectroscopy: molecular complexing in solution and in
      living cells.
AB  - FCS is an important technique for biophysicists, biochemists, and cell
      biologists. FCS represents an example of how one can make use of the microscope
      and electronics to extract information beyond the resolution limit of classical
      optics. It can be used to study single-molecules both in solution and in living
      cells and can be used to monitor a wide variety of macromolecular interactions.
      When used as an in vitro technique, FCS measurements are easy to conduct and can
      be made on simplified instrumentation. When used in vivo on living cells, many
      additional factors must be considered when evaluating experimental data. Despite
      these concerns, FCS represents a new approach that has broad applicability for
      the determination of molecular stoichiometry both in vivo and in vitro for a
      variety of membrane and soluble receptor systems.

PMID- 14719346
TI  - Should we reconsider triggers for red blood cell transfusion?
AB  - Very few randomized controlled trials on the benefits of red blood cell (RBC)
      transfusions in humans have been published. Consequently, most clinical practice
      guidelines remain based on expert opinion, animal studies and the limited human
      trials available. In the absence of definitive outcome studies, numerous
      theoretical arguments have been put forward either to support or to condone the
      classic transfusion threshold of 10 g/dL. However, the limited data available
      from randomized controlled trials suggest that a restrictive transfusion strategy
      (transfusion threshold between 7 and 8 g/dL) is associated with decreased
      transfusion requirements, that overall morbidity (including cardiac morbidity)
      and mortality, hemodynamic, pulmonary and oxygen transport variables are not
      different between restrictive and liberal transfusion strategies and, finally,
      that a restrictive transfusion strategy is not associated with increased adverse
      outcomes. In fact, a restrictive strategy may be associated with decreased
      adverse outcomes in younger and less sick critical care patients. The majority of
      existing guidelines conclude that transfusion is rarely indicated when the
      hemoglobin concentration is greater than 10 g/dL and is almost always indicated
      when it falls below a threshold of 6 g/dL in healthy, stable patients or more in
      older, sicker patients. In anesthetized patients, this threshold should be
      modulated by factors related to the dynamic nature of surgery, such as
      uncontrolled hemorrhage, coagulopathy, etc. Since transfusions are administered
      to correct inadequate oxygen delivery, whether global or regional, reliable
      monitors of tissue oxygenation will be required to study the benefits (or lack
      thereof) of RBC transfusions. The quest for a universal transfusion trigger, the
      holy grail of transfusion medicine, must be abandoned. All RBC transfusions must
      be tailored to the patient's needs, at the moment the need arises. In conclusion
      most published recommendations are appropriate but their conclusions are limited,
      as they are commensurate with existing knowledge. Reliable monitors to guide
      transfusion therapy and well conducted trials to determine optimal transfusion
      strategies are required.

PMID- 14719347
TI  - Does blood transfusion increase risk of postoperative complications?

PMID- 14719348
TI  - Perfluorocarbons and haemoglobin solutions: will they ever reach clinical
      practice?

PMID- 14719349
TI  - New antithrombotic agents: unsolved issues.

PMID- 14719350
TI  - Blood transfusion strategy in pediatrics.

PMID- 14719351
TI  - When, why and how to order blood?

PMID- 14719352
TI  - Refusing medical treatment: legal aspects.

PMID- 14719353
TI  - Antifibrinolytics.

PMID- 14719354
TI  - Crystalloids and colloids. A personal view on their perioperative use.

PMID- 14719355
TI  - rFVIIa (Novoseven): the new panacea?

PMID- 14719356
TI  - Raymond Urgel Lemieux.

PMID- 14719357
TI  - Development of an automated oligosaccharide synthesizer.

PMID- 14719358
TI  - Synthesis and reactions of unsaturated sugars.

PMID- 14719359
TI  - Chemistry of anhydro sugars.

PMID- 14719360
TI  - Acids and other products of oxidation of sugars.

PMID- 14719361
TI  - Oxidative reactions and degradations of sugars and polysaccharides.

PMID- 14719362
TI  - 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids in bacterial glycopolymers:
      chemistry and biochemistry.

PMID- 14719363
TI  - Varicella virus-mononuclear cell interaction.
AB  - Varicella zoster virus (VZV) causes varicella (chickenpox), becomes latent in
      cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later
      to produce zoster (shingles). The main complication of zoster is postherpetic
      neuralgia (PHN), pain that persists for months and often years after zoster. VZV
      also causes chronic radicular pain without rash (zoster sine herpete). Viremia is
      associated with each stage of VZV infection. Viral DNA has been found in
      peripheral blood mononuclear cells (MNCs) of patients with varicella, zoster,
      PHN, and zoster sine herpete. In varicella, viremia contributes to the widespread
      distribution of skin lesions and infection of multiple organs. Although the role
      of viremia in other VZV-associated diseases is not as clear, the detection of VZV
      DNA (and sometimes VZV RNA and proteins) helps diagnose neurological diseases
      produced by VZV, has indicated that PHN may reflect a chronic VZV ganglionitis,
      and has established that VZV reactivates subclinically, especially in
      immunocompromised humans. In vitro studies have established that VZV can
      productively infect MNCs for a short time and have identified the subpopulations
      of MNCs that are infected. Finally, simian varicella virus (SVV) infection of
      nonhuman primates shares clinical, pathological, and virologic features with VZV
      in humans. Like VZV, SV viremia in nonhuman primates during acute infection plays
      an important role in the pathogenesis of SVV. Infectious virus can be isolated
      from MNCs, and SVV DNA can be detected in MNCs during varicella. Further, SVV DNA
      can be detected for months in MNCs of monkeys after experimental infection with
      SVV. Herein, we review the current literature related to VZV infection of MNCs
      during naturally occurring varicella, PHN, and zoster sine herpete in humans,
      including studies of experimental infection of human MNCs with VZV. We also
      review SVV MNC interaction during naturally occurring simian varicella and after
      experimental infection of primates with SVV.

PMID- 14719364
TI  - Evolution of cell recognition by viruses: a source of biological novelty with
      medical implications.

PMID- 14719365
TI  - Infectious pancreatic necrosis virus: biology, pathogenesis, and diagnostic
      methods.

PMID- 14719366
TI  - Structures of picorna-like plant viruses: implications and applications.

PMID- 14719367
TI  - Cucumoviruses.
AB  - Research on the molecular biology of cucumoviruses and their plant-virus
      interactions has been very extensive in the last decade. Cucumovirus genome
      structures have been analyzed, giving new insights into their genetic
      variability, evolution, and taxonomy. A new viral gene has been discovered, and
      its role in promoting virus infection has been delineated. The localization and
      various functions of each viral-encoded gene product have been established. The
      particle structures of Cucumber mosaic virus (CMV) and Tomato aspermy virus have
      been determined. Pathogenicity domains have been mapped, and barriers to virus
      infection have been localized. The movement pathways of the viruses in some hosts
      have been discerned, and viral mutants affecting the movement processes have been
      identified. Host responses to viral infection have been characterized, both
      temporally and spatially. Progress has been made in determining the mechanisms of
      replication, gene expression, and transmission of CMV. The pathogenicity
      determinants of various satellite RNAs have been characterized, and the
      importance of secondary structure in satellite RNA-mediated interactions has been
      recognized. Novel plant genes specifying resistance to infection by CMV have been
      identified. In some cases, these genes have been mapped, and one resistance gene
      to CMV has been isolated and characterized. Pathogen-derived resistance has been
      demonstrated against CMV using various segments of the CMV genome, and the
      mechanisms of some of these forms of resistances have been analyzed. Finally, the
      nature of synergistic interactions between CMV and other viruses has been
      characterized. This review highlights these various achievements in the context
      of the previous work on the biology of cucumoviruses and their interactions with
      plants.

PMID- 14719368
TI  - Coevolution of viruses with hosts and vectors and possible paleontology.
AB  - The coevolution of viruses with their hosts and vectors depends on the evolution
      of the hosts and vectors coupled with factors involved in virus evolution. The
      long-term perspective involves the origin of life forms, the evolution of host
      and vector (especially arthropods) kingdoms and families, and changes in
      biological diversity induced mainly by the last five great extinctions. In the
      medium term, the diversification of hosts and vectors is important, and in the
      short term, recent events, especially humans, have had a great impact on virus
      coevolution. As there are few, if any, examples of conventional fossils of
      viruses, evidence for their evolution related to host and vector evolution is
      being found from other sources, especially virus-induced cellular structures and
      recent developments in molecular biology. Recognizing these other sources is
      becoming important for paleontologists gaining an understanding of the influence
      that viruses have had on the development of higher organisms.

PMID- 14719369
TI  - Bariatric surgery may become a self-pay service.

PMID- 14719370
TI  - Consolidation of MCOs will force IDN mergers.

PMID- 14719371
TI  - Hospitals given incentives to improve access to costly care.

PMID- 14719372
TI  - The organ trail: express versus presumed consent as paths to blaze in solving a
      critical shortage.

PMID- 14719373
TI  - Signaling by the CD19/CD21 complex on B cells.
AB  - Early studies, largely based on in vitro models, revealed potential functional
      roles for the components of the CD19/21/81 complex in B cell proliferation and
      antibody production. These studies also identified signal transduction pathways
      linked to these receptors. Over the last decade, studies on knockout mice defined
      the biologic functions of CD19, CD21 and CD81. This review focuses on current
      attempts to use these receptors as tools to understand how the immune system
      regulates responsiveness and tolerance, while correlating specific biochemical
      pathways with biologic function.

PMID- 14719374
TI  - Complement receptor 2 and autoimmunity.
AB  - Complement receptor 2 (CR2/CD21) plays a major role in the immune response by
      linking innate and adaptive immunity to foreign pathogens and proteins. In
      addition, several lines of evidence strongly support a role for CR2 in the
      maintenance of tolerance to self-antigens. Both the absence of CR2 expression
      (along with the alternatively spliced gene product CR1) and the presence of a
      dysfunctional CR2 protein are tightly associated with the development of
      autoreactivity to nuclear antigens. Altered levels of expression of CR2 in
      patients with systemic lupus erythematosus support a clinically relevant role for
      this phenotype. Several possible mechanisms could underlie the loss of self
      tolerance related to CR2, but the effect is most likely related to the failure of
      one or more specific checkpoints that limit autoreactivity during B cell
      development and immune reactions.

PMID- 14719375
TI  - Apoptosis, complement and systemic lupus erythematosus: a mechanistic view.
AB  - Deficiencies in the classical pathway of the complement system have been
      implicated in the etiology and pathogenesis of systemic lupus erythematosus (SLE)
      for several decades. Recent advances have suggested that this link is due to a
      critical role of complement in the recognition and clearance of the cellular
      remnants of apoptosis. In this review, we summarize the role of apoptosis in
      generation of an autoimmune response, and we integrate recent advances that link
      apoptosis, complement activation and the etiopathogenesis of SLE.

PMID- 14719376
TI  - Role of C1q and C1q receptors in the pathogenesis of systemic lupus
      erythematosus.
AB  - The association between C1q and autoimmune diseases such as rheumatoid arthritis
      and systemic lupus erythematosus (SLE) is well established. Deficiency in C1q is
      considered to be a strong susceptibility factor and is corroborated by the fact
      that > or = 92% of the known cases of hereditary deficiency in C1q develop
      rheumatic disease. Furthermore, the observation of the presence of high-affinity
      autoantibodies against C1q antibodies in patients with SLE provides a strong
      correlation between these antibodies and the inflammatory processes that occur in
      this disease. Recent evidence using C1q-deficient mice has shown the presence of
      glomerulonephritis with immune deposits and a large number of apoptotic bodies in
      the diseased glomeruli suggesting a defect in the clearance of apoptotic cell by
      macrophages and dendritic cells (DCs). Although these data are consistent with
      the hypothesis that C1q deficiency may induce a generalized failure to clear
      immune complexes and apoptotic cells, this concept alone cannot wholly explain
      why individuals with C1q deficiency are prone to develop SLE. Therefore, C1q
      alone or in conjunction with other surface molecules must play a much more
      fundamental role in immunoregulation, especially those processes that regulate T
      cell function and tolerance. In support of this hypothesis is the finding that
      C1q causes inhibition of mitrogen-induced T cell-proliferative response by
      interaction with C1q receptors. Furthermore, macrophages and possibly DCs not
      only synthesize but also display C1q as a type II cell surface molecule,
      especially at sites of inflammation. Although it is not yet known what role the
      surface-expressed C1q plays, it is tempting to assume that it plays a role in the
      priming of naive T cells by DCs. This work will review the current concepts of
      the role of C1q and C1q receptors in autoimmunity.

PMID- 14719377
TI  - The intricate role of complement component C4 in human systemic lupus
      erythematosus.
AB  - It was observed about 50 years ago that low serum complement activity or low
      protein concentrations of complement C4 concurred with disease activities of
      systemic lupus erythematosus (SLE). Complete deficiencies of complement
      components C4A and C4B, albeit rare in human populations, are among the strongest
      genetic risk factors for SLE or lupus-like disease, across HLA haplotypes and
      racial backgrounds. However, whether heterozygous or partial deficiency of C4A
      (C4AQ0) or C4B (C4BQ0) is a predisposing factor for SLE has been a highly
      controversial topic. In this review we critically analyzed past epidemiologic
      studies on deficiency of C4A or C4B in human SLE. Cumulative results from more
      than 35 different studies revealed that heterozygous and homozygous deficiencies
      of C4A were present in 40-60% of SLE patients from almost all ethnic groups or
      races investigated, which included northern and central Europeans, Anglo-Saxons,
      Caucasians in the US, African Americans, Asian Chinese, Koreans and Japanese. In
      addition, French SLE and control populations had relatively low frequencies of
      C4AQ0, but the difference between the patient and control groups was
      statistically significant. The relative risk of C4AQ0 in SLE varied between 2.3
      and 5.3 among different ethnic groups. In Caucasian and African SLE patients, the
      two major causes for C4AQ0 are (1) the presence of a mono-S RCCX (RP-C4-CYP21
      TNX) module with a single, short C4B gene in the major histocompatibility
      complex; and (2) a 2-bp insertion into the sequence for codon 1213 at exon 29 of
      the mutant C4A gene. Both mono-S structures and 2-bp insertion in exon 29 are
      absent or extremely rare in the C4AQ0 of Oriental SLE patients. The highly
      significant association of C4AQ0 with SLE across multiple HLA haplotypes and
      ethnic groups, and the presence of different mechanisms leading to a C4A protein
      deficiency among SLE patients suggested that deficiency or low expression level
      of C4A protein is a primary risk factor for SLE disease susceptibility per se. On
      the other hand, Spanish, Mexican, Australian Aborigine SLE patients had increased
      frequencies of C4B deficiency instead of C4A deficiency. Such observations
      underscore the importance of both C4A and C4B proteins in the fine control of
      autoimmunity. Different racial and genetic backgrounds could change the
      thresholds for the requirement of C4A or C4B protein levels in immune tolerance
      and immune regulation. Most past epidemiological studies of C4 in human SLE did
      not consider the polygenic and gene size variations of C4A and C4B. In addition,
      many studies were overly dependent on phenotypic observations or methods that did
      not distinguish differential C4A and C4B protein expression caused by unequal
      gene number or different gene size from the absence of a functional C4A or C4B
      gene. For further longitudinal studies on clinical manifestations of SLE, it
      would be informative to stratify the patients with accurately defined C4A and C4B
      genotypes. Likewise, elucidation of epistatic genetic factors interacting with
      C4AQ0 would provide important insights into the intricate roles of C4 in SLE
      disease susceptibility and pathogenesis.

PMID- 14719378
TI  - The role of complement in the antiphospholipid syndrome.
AB  - The anti-phospholipid syndrome (APS) is characterized by recurrent fetal loss,
      vascular thrombosis and thrombocytopenia occurring in the presence of
      antiphospholipid (aPL) antibodies. We hypothesized that aPL antibodies activate
      complement in the placenta, generating split products that mediate placental
      injury and lead to fetal loss and growth restriction, and that complement
      activation by aPL antibodies in other vascular areas causes inflammation and
      thrombophilia. Here we review studies in a murine model of APS in which human aPL
      antibodies are passively transferred into pregnant mice. Blockade of complement
      activation using a C3 convertase inhibitor or genetic deletion of C3 protected
      mice from pregnancy complications induced by aPL antibodies. These findings
      demonstrate that complement activation is a central mechanism in aPL antibody
      induced pregnancy loss and fetal growth restriction. Although the cause of tissue
      injury in APS is likely to prove multifactorial, we have shown that complement
      activation is an absolute requirement for the most serious phenotypic outcomes,
      pregnancy complications and thrombosis, and, therefore, that this pathway acts
      upstream of other important effector mechanisms.

PMID- 14719379
TI  - Autoimmunity, complement activation, tissue injury and reciprocal effects.
AB  - Proteins of the complement system limit the expression of systemic autoimmunity
      by raising the threshold for negative selection and, in their absence,
      autoreactive lymphocytes seem to enter the periphery. On the other hand,
      complement activation in the course of systemic autoimmunity leads to tissue
      injury in a number of ways including direct lysis of cells, modification of cell
      function and by contributing to the formation of immune complexes. Excessive
      complement activation as a result of a regulator component deficiency leads to
      tissue injury that mimics that seen in autoimmune disease. Complement activation
      occurs during tissue injury and contributes in a major way to the expression of
      pathology. It appears that natural antibodies represent an early culprit in
      tissue injury following ischemia/reperfusion injury. Natural antibodies and
      probably autoantibodies present in sera of patients with systemic autoimmune
      disease bind to tissues already exposed to a damaging insult, activate complement
      and produce pathology.

PMID- 14719380
TI  - Complement and autoimmune glomerular diseases.
AB  - The renal glomerulus is the specialized structure in the kidney responsible for
      generating over 150 liters of plasma ultrafiltrate per day in humans. Certain
      characteristics of this structure favor involvement in autoimmune diseases.
      Formation of immune complexes in the glomerulus, either deposited from the
      circulation or generated in situ, can activate the complement system. Active
      products of this system include the anaphylatoxins C3a and C5a, C3b, which
      covalently associates with immune complexes, and the C5b-9 membrane attack
      complex. If complement is activated in a site accessible to blood constituents,
      such as in the subendothelial and mesangial regions, generated C3a, C5a and C3b
      can interact with their respective receptors on inflammatory cells to lead to an
      exudative lesion. In addition, intrinsic glomerular cells bearing relevant
      receptors may also be activated and can proliferate to contribute to the
      inflammation. In a privileged site such as the subepithelial region, complement
      activation products are not accessible to blood cells, and as such, the resultant
      pathology is noninflammatory. In this setting, effects of C5b-9 predominate,
      which include activation and injury of cells through still incompletely
      characterized pathways. Various means to alter the complement pathway are now
      available, including antibody inhibitors and recombinant proteins based upon
      naturally occurring complement regulators. The use of these agents, as well as
      mice in which individual components of the complement system have been deleted,
      has given a great deal of insight into how the complement system is involved in
      glomerular disease. The ability to manipulate the complement pathway is now a
      reality in a clinical setting, yet conclusive human studies are difficult to
      achieve.

PMID- 14719381
TI  - Membrane complement regulatory proteins in autoimmune and inflammatory tissue
      injury.
AB  - The complement system plays a complex role in the pathogenesis of autoimmune
      diseases. It inhibits autoimmunity development by helping to maintain self
      tolerance and/or by facilitating the disposal of immune complexes and apoptotic
      cell antigens. On the other hand, complement activation is thought to contribute
      significantly to end organ damage in antibody-mediated autoimmune and
      inflammatory conditions, although the relevant importance of complement and Fe
      receptor pathways in these processes has recently been debated. To avoid
      autologous complement-mediated tissue injury, host cells normally express a
      number of soluble and membrane-bound complement regulatory proteins. Recent
      studies with gene knockout mice have suggested that membrane-bound complement
      regulatory proteins may critically determine the sensitivity of host tissues to
      complement injury in autoimmune and inflammatory disorders. Evidence is also
      accumulating to support the hypothesis that membrane complement regulatory
      proteins may not only inhibit complement-mediated injury during the effector
      phase of autoimmunity but also influence the adaptive immune response through
      complement-dependent or -independent mechanisms. The latter mechanism is likely
      related to their potential as cell surface signaling molecules.

PMID- 14719382
TI  - Hemodialysis vascular access and peritoneal dialysis access. Preface.

PMID- 14719383
TI  - History and evolution of the vascular access for hemodialysis.

PMID- 14719384
TI  - Epidemiology of vascular access for hemodialysis and related practice patterns.
AB  - VA serves as a lifeline for HD patients. VA-related expenditures are the largest
      component of dialysis-related costs. Wide variations in VA practices and outcomes
      around the world have emerged from analysis of the DOPPS data. Both patient and
      practice pattern-related factors determine type of VA placed as well as VA
      outcomes. Type of VA is associated with patient survival after adjustment for
      case mix. A multidisciplinary approach is crucial for success of any VA program
      with emphasis on pre-ESRD planning and implementation. AVF should serve as the
      gold standard. Use of catheters should be minimal, but this will likely remain a
      challenge for some time. Observational data suggest that earlier cannulation of
      AVF may not be as deleterious as previously thought. Clinical trials are sorely
      needed in many aspects of VA management to improve both VA and patient outcomes.

PMID- 14719385
TI  - Vascular access: issues and management.

PMID- 14719386
TI  - Arteriovenous fistulas: different types and surgical techniques.

PMID- 14719387
TI  - Vascular grafts for hemodialysis: types, sites and techniques.

PMID- 14719388
TI  - Temporary vascular access for hemodialysis treatment. Current guidelines and
      future directions.

PMID- 14719389
TI  - Hemodialysis catheters: materials, design and manufacturing.

PMID- 14719391
TI  - Long-term vascular access: the Tesio catheter.

PMID- 14719390
TI  - Chronic central venous catheters for dialysis and the Ash Split Cath catheter:
      rationale and clinical experience.

PMID- 14719392
TI  - Vascular access for acute extracorporeal renal replacement therapies.

PMID- 14719393
TI  - Totally implantable subcutaneous devices for hemodialysis access.
AB  - Subcutaneous hemodialysis access systems represent a uniquely different
      hemodialysis access option. The ideal role for these devices is to help patients
      to achieve a functioning AV fistula by providing temporary access while patients
      are waiting for the creation or maturation of an AV fistula. An ideal bridge
      device would allow for immediate use following placement, provide blood flow
      rates sufficient to ensure adequate dialysis, have a low complication rate, and
      have sufficient length of technical survival to allow AV fistula development and
      maturation without the need for device replacement. Clinical data reported to
      date supports the use of subcutaneous hemodialysis access systems as a bridge
      device instead of a hemodialysis catheter [11, 12, 17-20]. The increased emphasis
      on AV fistula placements in patient populations who are at higher risk of having
      fistulas that fail to mature increases the need for a bridge device which
      provides improved outcomes during longer maturation periods especially in
      patients in whom more than one fistula attempt is made or for patients who are
      receiving upper arm fistulas [21, 36]. Several studies have also documented the
      utility of subcutaneous hemodialysis access systems in catheter-dependent
      patients who have exhausted other access options [12-15, 19, 20]. The hope
      offered for improved outcomes in this patient population should be tempered by
      realistic expectations for device performance especially in patients with
      significant morbidities, poor vasculature, a history of poorly performing
      hemodialysis catheters, or multiple catheter-related infections. Totally
      subcutaneous hemodialysis access systems offer a unique option for ESRD patients.
      The development of these devices represent a key step towards improving dialysis
      delivery and hemodialysis vascular access-related outcomes. Following recommended
      procedures for implanting, accessing and maintaining these devices is key towards
      achieving optimal device performance.

PMID- 14719394
TI  - Complications of the vascular access for hemodialysis.

PMID- 14719395
TI  - Monitoring techniques of vascular access.

PMID- 14719396
TI  - Hematocrit-based measurements of vascular access flow rate.

PMID- 14719397
TI  - Hemodynamics of the hemodialysis access: implications for clinical management.

PMID- 14719398
TI  - Vascular access recirculation: measurement and clinical implications.

PMID- 14719399
TI  - Arteriovenous vascular access flow measurement: accuracy and clinical
      implications.

PMID- 14719400
TI  - Interventional techniques for malfunctioning accesses.

PMID- 14719401
TI  - Quality assurance and continuous quality improvement programs for vascular access
      care.

PMID- 14719402
TI  - Systemic barriers to vascular access care: implications for clinical outcomes.

PMID- 14719403
TI  - The vascular access: a long-term patient's considerations and reflections.

PMID- 14719404
TI  - An experimental temporary vascular access catheter for intracorporeal plasma
      separation.

PMID- 14719405
TI  - History and development of the access for peritoneal dialysis.

PMID- 14719406
TI  - Techniques of peritoneal catheter insertion.

PMID- 14719407
TI  - Maintenance of functioning PD access and management of complications.

PMID- 14719408
TI  - Catheter exit site care in the long-term.

PMID- 14719409
TI  - Conditions leading to catheter removal or substitution.

PMID- 14719410
TI  - New catheter design for continuous flow peritoneal dialysis.

PMID- 14719411
TI  - Smoking and long-term effects.

PMID- 14719412
TI  - Weight concern, dieting and eating behaviors. A survey of Israeli high school
      girls.
AB  - The main goal of the present study was to explore some of the risk-factor
      variables for eating disorders among Israeli junior high and high school
      adolescent girls (12-18 years old) from different residential areas in the
      northern district of Israel. Additionally, this study examined and identified
      which group was most prone to develop disordered eating behaviors and attitudes.
      METHOD: A representative sample of 1,316 Jewish adolescent females from five
      Israeli school sub-groups and from five different residential areas was selected
      proportionally to various school sub-groups and residential areas. The Eating
      Disorder Inventory-2 (EDI-2) was the assessment tool used, yielding scores on 11
      sub-scales. RESULTS: In regard to age, the 16.6-18 year-olds were found to have
      significantly higher total EDI-2 scores, as compared to the other age groups.
      Girls aged 16.6 and up were found to have the highest score in six sub-scales out
      of eleven. As for different types of schools in different residential settings,
      the secular boarding school sub-group had the significantly highest scores, while
      the kibbutz sub-group had the lowest scores for the total EDI-2, as well as for
      most subscales. The majority of scores for the other school sub-groups fell
      midway between the two extreme groups. DISCUSSION: The results are discussed in
      terms of cultural, religious, ethnic, and socioeconomic influences. CONCLUSION:
      The results highlight the need to conduct a systematic methodological study
      comparing various psychological and socioeconomic factors, including maladaptive
      eating behavior in different types of religious residential schools.

PMID- 14719413
TI  - Teenage smoking: some problems with interpreting the evidence.
AB  - This paper attempts to address the methodological problem of disentangling
      complex interrelationships between teenage smoking and other variables when using
      survey data. As in any research based on survey data, it is difficult to
      distinguish systematic from random patterns due to other variables. METHOD: A
      pragmatic approach of classifying variables into three groups of objectively
      measured demographic, socio-environmental variables and subjectively measured
      sociopsychological variables was adopted. A secondary cross-sectional survey data
      source was used to fit and test three models. RESULTS: The results suggest socio
      environmental and socio-psychological variables may effect teenage smoking
      through demographic and some other variables not measured in the survey.
      CONCLUSION: Standard statistical techniques are unable to distinguish between the
      different effects and their impact on the outcome. However, they can be used to
      re-examine and re-evaluate the results as potential evidence. A re-assessment of
      results suggests that effects of variables reported in the literature on teenage
      smoking may be over estimated. For example, self-esteem may not be as important
      and the role of peer pressure may not be as clear as it has been made out to be.

PMID- 14719414
TI  - A comparison of pregnancy and child health outcomes between teenage and adult
      mothers in the slums of Nairobi, Kenya.
AB  - The study assessed and compared pregnancy and child health outcomes of teenage
      (aged less than 20 years) and adult (20-34 years of age) mothers. A total of 226
      teenage and 205 adult mothers met the study criteria out of the 3,256 women in
      the reproductive age group (15-49 years) and 318 adolescent girls (12-14 years of
      age) covered by the Nairobi Cross-sectional Slums Survey (NCSS). The main
      comparison involved socio-demographic variables, events during pregnancy,
      obstetric outcome, child morbidity and mortality and care provided during an
      illness episode. Results showed that a significantly higher percentage of teenage
      mothers and their partners had lower educational achievement compared with adult
      mothers and their partners. They were more likely to be economically
      disadvantaged than the adult mothers. Teenage mothers and their parents were also
      less likely to have ever been married. The two groups of mothers were comparable
      in terms of the rate and timing of antenatal care visits, place of delivery, rate
      of operative deliveries, reported size of the baby at birth, child vaccination
      status and reported morbidity and health care practice during an illness episode.
      The index child was alive during the survey period for 89.4% of the teenage and
      96.6% of the adult mothers (OR = 3.36; 95% CI = 1.34, 8.79; P = 0.004). Child
      survival rates in the two groups of mothers were found to be quite similar after
      controlled analysis for the influence of socio-economic factors. The study
      concluded that bad obstetric outcomes were not associated with maternal age.
      Although teenage and adult mothers were not significantly different on child
      health practices, children born to the former group died most frequently probably
      due to their poor socioeconomic achievements.

PMID- 14719415
TI  - Teenage pregnancy experiences in rural Kenya.
AB  - This community-based survey describes the socio-economic determinants of teenage
      pregnancy, experiences of health problems during pregnancy, and health care
      utilization patterns among adolescents (12-19 years old) in rural Kenya.
      Characteristics of adolescents with repeated pregnancy experiences were compared
      with first-time pregnancies. The survey covered 3,132 households from 32 randomly
      selected communities and 1,247 adolescents were interviewed. Data were collected
      retrospectively through quantitative and qualitative methods. Results showed that
      572 (45.9%) adolescents had had sexual intercourse in the past, and of these, 245
      (42.8%) had been pregnant at least once. A significant majority of adolescents
      who had been pregnant were not attending school during the survey period. Fifty
      six percent of the first pregnancies occurred while the girl was single. Compared
      with repeat pregnancies, first pregnancies were more likely to be reported as
      unwanted (OR = 2.4; 95% CI = 1.1, 5.3). Antenatal care attendance, place of
      delivery and pregnancy outcomes were not significantly different for first-time
      and repeat pregnancies. Adolescents' reports on health problems during pregnancy,
      labour and in the post-partum period were not associated with parity or with age
      (< 16 years old). A lower proportion of younger primigravidae sought medical
      attention for health problems that arose during pregnancy (OR = 2.3; 95% CI =
      1.1, 4.8) and labor (OR = 3.6; 95% CI = 1.5, 8.7). In conclusion, the study
      highlighted major unmet reproductive health needs of adolescents in this region.
      Age and gravida influenced health care seeking which could increase the chances
      of serious life threatening complications among young primigravidae.

PMID- 14719416
TI  - Assisted delivery in the teenage population: the effect of inter-hospital
      variation, deprivation, and age.
AB  - The objective was to determine the relationship between the risk of assisted
      delivery in women aged under 20 years and place of treatment, deprivation and
      age. DESIGN: Cross sectional survey utilising routinely collected hospitals
      admissions data. POPULATION: Teenagers (women aged under 20 years) whose delivery
      resulted in a hospital admission in the period April 1st 1994 to March 31st 1997
      in the Trent Health Region of England. METHODS: The cases were identified using
      Office of Population Census and Surveys procedural codes, and International
      Classification of Diseases diagnostic codes associated with delivery. Variables
      collected included type of delivery, age at delivery and place of treatment. The
      data were analysed using the chi-square test for categorical data and the
      independent samples t-test for continuous data. Logistic regression analysis was
      used to calculate adjusted odds ratios for the variables of type of assisted
      delivery and place of treatment. MAIN OUTCOME MEASURES: Factors associated with
      increased risk of assisted delivery. RESULTS: There was variation in rates of
      instrumental delivery between hospitals, with two having a significantly
      increased risk of assisted delivery, suggesting that place of treatment may be a
      factor in the risk of teenage patients experiencing an assisted delivery. There
      was also a large amount of variation in terms of the risk of experiencing a
      forceps or vacuum extraction compared to caesarean section. Age (under 16 years
      and 16-19 years of age) had no effect on the risk of a teenage patient
      experiencing an assisted delivery (X2 = 2.59 df = 1 P = 0.11 OR 1.27 (95% CI 0.94
      to 1.72)). Similarly, teenagers who experience an assisted delivery were not more
      likely to come from a more deprived area than teenagers who did not have an
      assisted delivery (P = 0.189). CONCLUSIONS: The risk of assisted delivery varied
      between hospitals, suggesting that this factor is important in terms of a young
      women's risk of an assisted delivery. The young women in this study who had
      experienced an assisted delivery were not significantly different to young women
      who had a normal delivery. They were not more likely to be aged under 16 years of
      age, and were not more likely to be from a more deprived area.

PMID- 14719417
TI  - Analysis of prevalence, triggers, risk factors and the related socio-economic
      effects of childhood asthma in the Student Lung Health Survey (SLHS) database,
      Canada 1996.
AB  - The purpose of this study was to provide information to improve the management of
      childhood asthma in Canada. The Student Lung Health Survey (SLHS) was conducted
      as a stratified and multi-staged cluster survey across Canada in 1996. It
      included a total of 136 public, private and separate schools in nine health
      units. The target study population was schoolchildren aged 5 to 19 years. Among
      all 5-19 years old students, the prevalence of asthma was 13.0%, with the
      prevalence for males being higher than for females, the adjusted Odds Ratio (OR)
      was 1.17, (95% CI 1.14-1.19) for males, in comparison with females. The
      prevalence in the 15-19 age group was higher than that in the 5-9 and 10-14 age
      group in females, but it was higher in the 5-9 and 10-14 age group than in the 15
      19 age group in males. The mean delay from the onset of symptoms to time of first
      diagnosis was 1, 0.4 and 0.3 years for the 1-4, 5-9 and 10-14 age group
      respectively. However, there was no delay in the 15-19 group. The prevalence of
      asthma in Prince Edward Island (17.9%), Halifax (17.1%), and Kingston (16.1%) was
      higher than that in Saskatoon (10.0%). Sherbrooke (9.7%) and Kelowna (11.9%). The
      proportion of asthma for students who smoked more than 11 cigarettes per day (OR
      = 1.41), were exposed to passive smoke in home (OR = 7.29), in car (OR = 4.71),
      and in school (OR = 4.24) or had a family income less than CAN$40,000 (OR =
      1.19), was significantly higher than groups without those factors. Risk factors
      and socio-economic status such as living conditions and environment, pets or
      plants in the home, parental education levels also affected the morbidity of
      asthma. The results of the SLHS study demonstrated the serious burden of
      childhood asthma, and asthma triggers, living and environmental conditions and
      lifestyle influence the prevalence and the effects of childhood asthma diagnosis,
      treatment, and education in Canada. Asthma is still a serious chronic condition
      for students and it influences their academic performance and their quality of
      life. The diagnostic methods and the practice guidelines for asthma control are
      useful for preventing and controlling asthma. These findings provide indications
      of interventions are being used for the control of asthma in Canada.

PMID- 14719418
TI  - Tamoxifen treatment for pubertal gynecomastia.
AB  - We evaluated the efficacy of the tamoxifen treatment in 37 patients with pubertal
      gynecomastia. All had distinct, easily palpable breast swellings with a diameter
      of over three cm. Pain, tenderness, and swelling associated with gynecomastia
      were reported by six patients. Eight of the patients were obese. One patient also
      suffered from varicocele. Pain and size reduction was seen in all patients with
      tamoxifen treatment. No long-term side effects of tamoxifen were observed. The
      dose of tamoxifen was increased in three patients due to poor response. Two of
      the treatment group had recurrence problem at follow-up. We did not need to refer
      any patient to surgery. Tamoxifen treatment is relatively non-toxic, may be
      beneficial and we think it should be considered for pubertal gynecomastia.

PMID- 14719419
TI  - Smoking and adolescence.
AB  - Nicotine is one of the most addictive substances known and tobacco use started in
      adolescence can over time become a serious addiction with long-term health
      consequences. Tobacco was brought from America to Europe and has been used not
      only in Indian rituals, but also for medical purposes. In the 1950s and 1960s the
      adverse effects were revealed and the health community came out against tobacco
      smoking. This short communication presents recent trends in American and Israeli
      adolescent smoking. Recent surveys have shown a decrease in adolescent smoking,
      but it is still important to continue to reduce the numbers of adolescents who
      become nicotine dependent. Both American and Israeli youth had a current
      prevalence of smoking of 28%, so clinicians and practitioners must therefore do
      their utmost to help prevent smoking onset and try to intervene early to stop
      smoking among adolescents.

PMID- 14719420
TI  - Physical activity, children and adolescents.
AB  - Adolescents and young adults benefit from physical activity, which should be
      continued later on in life. Healthy habits in adolescence must continue in
      adulthood. A majority of children and adolescents participate in physical
      activity, but this activity declines in adulthood. Data from several surveys on
      children and adolescents in the United States and Israel is presented.

PMID- 14719421
TI  - Local anaesthesia--the early evolution of spinal needles.

PMID- 14719422
TI  - Anaesthesia and isolated systolic hypertension--pathophysiology and anaesthesia
      risk.
AB  - This review examines the pathophysiology of isolated systolic hypertension,
      changing medical perspectives on this condition as a cardiovascular risk factor
      in the community and evolving evidence of it being an independent risk factor for
      perioperative morbidity and mortality. Hypertension is regarded as an added risk
      in anaesthesia. Continuation of antihypertensive medication through the
      perioperative period is an established principle. Studies supporting this
      practice have demonstrated greater perioperative haemodynamic stability in
      association with general anaesthesia and surgery in patients with treated
      hypertension compared to untreated hypertension. Therapy has historically focused
      on control of diastolic blood pressure, rather than systolic blood pressure.
      Recent clinical trial data and data from large observational studies show a
      closer association of systolic hypertension with both coronary heart disease and
      stroke compared with diastolic hypertension. This has led to recommendations for
      aggressive treatment of isolated systolic hypertension, especially in patients
      over 65 years old. The association between decreased compliance of the central
      systemic arteries and isolated systolic hypertension is well understood. The fact
      that this same pathology, lack of compliance of central arteries, can cause a
      decrease in diastolic blood pressure is not so well recognised. This means that,
      in patients with isolated systolic hypertension, decreasing diastolic blood
      pressure can be associated with worsening arterial disease and that systolic
      minus diastolic blood pressure may give a better indication of the problem.
      Anaesthetic assessment and technique should be studied and potentially revised in
      the light of these changes in perspective on isolated systolic hypertension.

PMID- 14719423
TI  - Procalcitonin: a marker of bacteraemia in SIRS.
AB  - A number of European studies have documented the ability of procalcitonin (PCT),
      a novel inflammatory marker, to discriminate patients with sepsis from those with
      other causes of systemic inflammatory response syndrome (SIRS). The aim of this
      study was to assess procalcitonin's performance in an Australian intensive care
      unit (ICU) setting to examine whether it could discriminate between these two
      conditions. One hundred and twenty-three consecutive adult ICU patients
      fulfilling criteria for SIRS were enlisted in the study. Over a period of five
      days, daily serum PCT and C-reactive protein (CRP) levels were measured. At least
      two sets of cultures were taken of blood, sputum/broncho-alveolar lavage (BAL)
      and urine. Other cultures were taken as clinically indicated. Questionnaires to
      ascertain clinical suspicion of sepsis were prospectively answered by the ICU
      senior registrars. PCT values were ten times higher in patients with positive
      blood cultures; CRP values were also significantly higher in the bacteraemic
      patients. Both PCT and CRP had a good ability to discriminate bacteraemia from
      non-infectious SIRS, with the area under receiver operating characteristics (ROC)
      curves for PCT being 0.8 and for CRP being 0.82. However neither PCT or CRP was
      able to discriminate patients with localized sepsis from those without. Utilizing
      both tests resulted in a more sensitive screen than either one alone, while PCT
      was a more accurate diagnostic test for bacteraemia than CRP. The PCT value also
      differed between those who died in hospital and those who survived. Measurement
      of PCT alone or in combination with CRP can aid discrimination of
      septicaemia/bacteriemia with associated SIRS from non-infectious SIRS in an
      Australian ICU setting.

PMID- 14719424
TI  - Levobupivacaine versus racemic bupivacaine in spinal anaesthesia for urological
      surgery.
AB  - Racemic bupivacaine is the most common local anaesthetic used intrathecally. This
      prospective, randomized, double-blind study compared the clinical efficacy and
      motor block of 0.5% levobupivacaine with 0.5% racemic bupivacaine in spinal
      anaesthesia for urological surgery. The surgery required an upper level of
      sensory block of at least the tenth thoracic dermatome. Fifty patients were
      recruited (levobupivacaine group n = 24; bupivacaine group n = 26). Spinal
      anaesthesia was achieved with 2.6 ml of study solution injected in the
      subarachnoid space at the lumbar 3/4 interspace. One patient from the
      levobupivacaine group was excluded due to technical failure. There were no
      significant differences between the two groups in the quality of sensory and
      motor block or in haemodynamic change. Anaesthesia was adequate and patient
      satisfaction good in all cases. We conclude that 0.5% levobupivacaine can be used
      as an alternative to 0.5% racemic bupivacaine in spinal anaesthesia for surgery
      when a sensory block to at least T10 is required.

PMID- 14719425
TI  - Severe cardiac failure associated with presumed jellyfish sting. Irukandji
      syndrome?
AB  - We present a retrospective review of twelve cases of Irukandji syndrome
      associated with pulmonary oedema. This is a life-threatening envenoming due to a
      presumed jellyfish sting throughout Northern Australia, although only one case
      occurred outside North Queensland. Patients presented with significant and
      ongoing pain, tachycardia and hypertension. Half the patients became hypotensive
      requiring inotropic support. Cardiac echocardiography revealed significant
      cardiac dysfunction. Six patients required ventilatory support. There was no
      death reported due to pulmonary oedema, but one patient died of intracerebral
      haemorrhage. We believe patients may develop a toxin associated cardiomyopathy,
      and jellyfish other than Carukia barnesi may be responsible. As there is
      confusion with nomenclature, Carukia barnesi should be known as the Barnes
      jellyfish, and the diagnosis of cardiotoxic marine envenoming is suggested for
      any patient who has been stung by a jellyfish, develops no or minimal skin
      markings, and develops cardiogenic pulmonary oedema associated with Irukandji
      syndrome.

PMID- 14719426
TI  - Combination of adenosine with prilocaine and lignocaine for brachial plexus block
      does not prolong postoperative analgesia.
AB  - Adenosine analogues have been used by subarachnoid injection for the treatment of
      inflammatory and neuropathic pain. There is no data on the use of adenosine in
      peripheral nerve blocks. The aim of the present study was to determine the
      analgesic efficacy of adenosine in combination with a local anaesthetic solution
      for brachial plexus (BP) block. With local ethics committee approval, 50
      consenting adult patients undergoing upper limb surgery were enrolled in this
      double-blind, prospective, randomized study. Patients with a history of
      bronchospastic disease were excluded. Patients were instructed not to take
      theophylline-containing drugs and beverages for at least one day before surgery
      or on the first postoperative day. A supraclavicular BP block was performed by
      injecting a mixture totalling 35 ml made up of prilocaine 1% 10 ml and lignocaine
      2% 20 ml with adrenaline 1:200,000, and adenosine 10 mg in 5 ml saline (Group 1)
      or 5 ml saline (Group 2) as a placebo control group. Postoperative analgesia was
      assessed by time to first rescue analgesia, analgesic consumption in the first 24
      hours, and VAS at rest at 4, 8, 12, 16, 20 and 24 hours. Side-effects were also
      noted. Vital signs were stable in both groups throughout the operation. There
      were no significant differences between the groups in onset of motor and sensory
      block. Time to first pain sensation from block was not significantly longer in
      the adenosine group (379 +/- 336 min) compared with controls (304 +/- 249 min,
      mean +/- SD, P = 0.14). Time to first analgesic requirements and analgesic
      consumption in the first 24 hours were also similar in both study groups. In the
      present study, the addition of adenosine to local anaesthetic in brachial plexus
      block did not significantly extend the duration of analgesia.

PMID- 14719427
TI  - The influence of a blood conserving device on anaemia in intensive care patients.
AB  - The contribution of iatrogenic blood loss through diagnostic testing to the
      anaemia of critical illness remains controversial. We measured the effect of an
      arterial line blood conservation device upon blood loss and anaemia in adult
      intensive care patients. This randomized controlled trial of 160 patients in a
      major Intensive Care Unit (ICU) compared a blood conservation device (Venous
      Arterial Blood Management Protection Plus, VAMP Plus system, Baxter Healthcare)
      (VAMP group) to a standard arterial pressure line set attached to an arterial
      catheter (control group). The primary outcome measured was the change in
      haemoglobin concentration (Hb) during each patient's ICU admission and the volume
      of blood lost through diagnostic testing in ICU was also recorded. Both groups of
      80 patients were matched for age, gender, severity of illness (APACHE II),
      baseline Hb on entry and ICU length of stay. Both groups had a similar (median
      [range]) change in Hb during ICU admission (VAMP-7 [-84 to +21] g/l; Control -4 [
      67 to +40] g/l; P = 0.33). The VAMP patients lost significantly less blood for
      diagnostic testing while in ICU (VAMP 63 [0 to 787] ml; Control 133 [7 to 1227]
      ml; P = 0.001). We conclude that the VAMP Plus system significantly reduced
      iatrogenic blood loss in critically ill patients, but this reduction did not
      affect the fall in Hb that accompanies critical illness.

PMID- 14719428
TI  - Decontamination issues and perceived reliability of the laryngoscope--a
      clinician's perspective.
AB  - The laryngoscope is identified as a potential vector for cross-infection. Case
      reports are presented, as are reports of bacterial and occult blood contamination
      of laryngoscope blades and handles. Infection control policies covering
      laryngoscope blade and handle processing are outlined relative to procedures of a
      teaching hospital department. Repeated decontamination of laryngoscope blades has
      resulted in a perceived decrease in reliability. This is reflected in a
      departmental survey where 86% of respondents consider the standard laryngoscope
      is only intermittently reliable and that there is room for improvement.

PMID- 14719429
TI  - Prolonged per-laryngeal endotracheal intubation in children: 40 years on.
AB  - Because tracheostomy has a very high complication rate in small children,
      prolonged mechanical ventilation was not performed satisfactorily in infants
      until a technique was developed that allowed prolonged per-laryngeal endotracheal
      intubation in children. Plastic polyvinyl chloride endotracheal tubes were
      introduced in the 1950s; they soften at body temperature, and are much less
      likely to cause subglottic stenosis than endotracheal tubes made from metal or
      rubber. The first account of prolonged per-laryngeal intubation of infants using
      polyvinyl chloride tubes was written by Dr Bernard Brandstater, and this
      remarkable document is reproduced here. It sets out all the important principles
      of endotracheal intubation in children: the tube must fit easily through the
      cricoid ring, it must be firmly fixed in place with the tip in the mid trachea,
      meticulous humidification and suction are essential, and the tube should be
      changed only if there are signs of obstruction.

PMID- 14719430
TI  - A patient with congenital complete heart block undergoing multiple exposures to
      general anaesthesia.
AB  - We present a patient with congenital complete heart block who underwent multiple
      anaesthetic exposures for eye examination and bilateral cataract surgery. The
      diagnosis was made during the first general anaesthetic. Various complications
      encountered during the multiple exposures are discussed.

PMID- 14719431
TI  - Acute myocardial injury caused by Sydney funnel-web spider (Atrax robustus)
      envenoming.
AB  - A 67-year-old female suffered envenoming by a Sydney funnel-web spider (Atrax
      robustus), complicated by ST elevation and elevated troponin levels consistent
      with an acute myocardial injury. She was treated primarily with funnel-web spider
      antivenom, admission to intensive care and initial respiratory support for acute
      pulmonary oedema. The mechanism by which funnel-web spider envenomation caused
      myocardial injury is unclear but follow-up nuclear studies in the patient
      demonstrated that she had minimal atherosclerotic disease.

PMID- 14719432
TI  - ARDS with severe hypoxia--aeromedical transportation during prone ventilation.
AB  - Severe hypoxia, despite maximal conventional respiratory support, is one of the
      few remaining limitations to aeromedical transportation. A case of a 35-year-old
      female, who was referred 36 hours following major trauma for transfer by air to a
      tertiary center, is presented. At the time of referral the PaO2/FiO2 ratio was
      48. Usual manoeuvres to improve oxygenation had only minimal impact. The patient
      was turned and subsequently transported prone with resultant improvement in
      PaO2/FiO2 ratio to 260. There were no patient- or transport-related adverse
      events. The implication of prone positioning during aeromedical transportation is
      discussed.

PMID- 14719434
TI  - Hazard of reinforced endotracheal tubes.

PMID- 14719433
TI  - Alert for perioperative visual loss: an unusual presentation of an orbital
      haemangioma during spinal surgery.
AB  - A 62-year-old man with a history of non-insulin-dependent diabetes mellitus,
      hypertension and obesity, presented for elective lumbar laminectomy for spinal
      canal stenosis. Twenty minutes after placement in the prone position, he
      developed left orbital proptosis. The surgery was deferred and a subsequent CT
      scan showed an orbital haemangioma. This case highlights the importance of
      meticulous attention to eye-care for patients in the prone position.

PMID- 14719435
TI  - Anaphylaxis to chlorhexidine-impregnated central venous catheter.

PMID- 14719436
TI  - Whitacre needle insertion technique.

PMID- 14719437
TI  - Recovery intervention to manage severe pain: comparing apples with oranges?

PMID- 14719438
TI  - Who spiked the fentanyl?

PMID- 14719439
TI  - Remifentanil and propofol during ophthalmic block.

PMID- 14719440
TI  - [Origin of "ectopic" pituitary adenomas].

PMID- 14719441
TI  - [Role of thallium SPECT for evaluating the effect of maintenance chemotherapy
      against malignant gliomas].
AB  - Thallium (Tl)-201 single-photon emission computed tomography (SPECT) is a useful
      tool for detecting brain tumors. In this study, we evaluated the utility of Tl
      201 SPECT for determining the effect of maintenance chemotherapy with ACNU
      (nimustine hydrochloride)/VCR (vincristine sulfate) against malignant gliomas.
      The cases were comprised of 16 glioma cases; 6 astrocytomas, 2 anaplastic
      astrocytomas, and 8 glioblastomas. We first analyzed the correlation between Tl
      201 uptake ratio and proliferative activity of the tumor, using Ki-67
      immunohistochemistry in 13 cases of glioma. The uptake ratio of Tl-201 correlated
      with the Ki-67 staining indices (SI), and a closer correlation was obtained using
      Tl-201 delayed images than with the early images. We also analyzed the
      chronological changes of Tl-201 uptake ratio and volume of abnormal area
      evaluated by MRI T2-weighted imaging (MRI T2WI), in 10 cases of malignant glioma
      during maintenance chemotherapy. The Tl-201 uptake ratio gradually decreased with
      the effect of maintenance chemotherapy, and the sensitivity was superior to MRI
      findings. Together with MRI, Tl-201 SPECT is considered to be a useful indicator
      for evaluating the effect of maintenance chemotherapy against malignant gliomas.

PMID- 14719442
TI  - [Clinical features and outcomes of 10 asymptomatic adult patients with moyamoya
      disease].
AB  - Recent development of non-invasive diagnostic technology, such as magnetic
      resonance imaging (MRI) and angiography (MRA), is believed to have made possible
      on increase in the diagnoses of asymptomatic moyamoya disease. However, no
      criteria have been established for the management of such cases. The present
      study aimed to clarify the natural history of asymptomatic moyamoya disease
      retrospectively. Ten patients were included in this study. None of them had
      experienced any episode due to moyamoya disease and were only incidentally
      diagnosed as having moyamoya disease. There were 4 males and 6 females. Their
      ages ranged from 30 to 67 years, with the mean age of 46.2. Cerebral angiography
      showed there was the tendency of disease progression in elder patients. MRI
      detected cerebral infarction in 3 of 10 patients (30%). Hemodynamic ischemia,
      such as impaired reactivity to acetazolamide and/or elevated oxygen extraction
      fraction, was observed in 4 of 10 patients. Only one patient underwent surgical
      revascularization. Antiplatelet or anticonvulsant medication was administered in
      5 of 10 patients. The mean follow-up period was 4.1 years, ranging from 0.5 to 13
      years. During follow-up periods, the moyamoya lesion markedly progressed and
      caused cerebral infarction in one patient. However, neither ischemic nor
      hemorrhagic stroke occurred in the other 9 patients. Multi-center nation-wide
      study should be planned to clarify the natural course of asymptomatic moyamoya
      disease and establish the management guidelines for patients with asymptomatic
      moyamoya disease.

PMID- 14719443
TI  - [A case of thoracic disc herniation with sudden onset paraplegia on toilet
      straining: case report].
AB  - Thoracic disc herniation is less common rather than cervical or lumbar
      herniation. Cases of sudden onset without trauma are especially rare. Generally,
      the neurological onset of disc herniation is caused by mechanical cord
      compression due to a protruded disc, and its onset is usually gradual. Ischemia
      is also considered as a factor of neurological onset. We report a case of a 78
      year-old male with sudden paraplegia while straining at the toilet. T2 weighted
      MR image on admission showed mild disc protrusion at the level of Th8-9 and
      intramedullary high signal intensity below the Th8-9 level. We speculate that
      Valsalva-like maneuver had led to the congestion of vertebral venous plexus or
      compression of the anterior spinal artery, and spinal ischemia occurred.

PMID- 14719444
TI  - [A case of brain abscess associated with asymptomatic multiple myeloma].
AB  - A 55-year-old male was admitted to our hospital because of confusion and mild
      weakness of his left arm and leg. His condition had taken a gradual turn for the
      worse for several months. Computed tomography (CT) demonstrated a mixed density
      mass with multiple cysts and massive perifocal edema. Magnetic resonance imaging
      (MRI) demonstrated an irregular-shaped mass with multiple cysts sized 6 x 4 x 6
      cm in the temporal lobe, which manifested mixed signal intensity on both the T1
      weighted image and the T2 weighted image. MRI also revealed massive perifocal
      edema and marked midline shift. Gd-DTPA study showed ring-like enhancement.
      Angiography showed no tumor stain and a suppressed right posterior cerebral
      artery. A right extended temporo-occipital craniotomy was performed to extirpate
      the abscess subtotally. The histological examination showed brain abscess and
      Gram stain of the pus revealed the presence of gram-positive bacilli. The gram
      positive bacillus, Corynebacterium only was subsequently cultured from the pus.
      After the operation his hemiparesis seemed to disappear. In spite of the
      treatment with multiple intravenous antibiotics, his hemiparesis worsened again.
      CT and MRI demonstrated recurrence of the brain abscess in the occipital lobe and
      marked perifocal edema. The second operation was performed and removed all the
      infected brain tissue with abscess. After the second operation, otorhinological
      and cardiovascular examinations were carried out, but no causal disease was
      found. Immunoelectrophoresis (total protein 12.2 g/d/) revealed the peak of M
      protein. Bone marrow revealed dysplasia of the plasma cell and he was diagnosed
      as having multiple myeloma that had made him an immunocompromised host.

PMID- 14719445
TI  - [A case of atypical meningioma associated with acute deterioration and cerebral
      herniation].
AB  - Brain tumors not uncommonly display a chronic course, with symptoms occurring
      insidiously. This case report describes a meningioma patient who presented sudden
      onset and rapidly progressing symptoms. She was 49 years old, a referred case
      from a nearby hospital, with severe headache and fever. This was also accompanied
      by unconsciousness and left hermiparesis which necessitated emergency brain CT
      and MRI scanning. A right temporal 5 cm ring enhancing lesion with massive
      surrounding edema was revealed. Despite osmotic diuretics to relieve brain edema,
      symptoms worsened, so decompressive right temporal craniotomy and total excision
      of the tumor was performed. This mass lesion was found to be extra axial, with
      histology revealing on atypical meningioma with massive necrosis. This rare case
      which is thought to be due to massive peritumoral edema, possibly from an
      ischemic occluded major feeder, conforms to glioma radiologically; while the
      clinical picture has a similarity to brain abscess. This case is presented as a
      reminder to neurosurgery practice that meningioma can also be a possibility when
      a ring enhancing cerebral mass in encountered and is accompanied by such a
      bizarre sudden and rapidly progressing neurologic condition.

PMID- 14719446
TI  - [Normalization of cerebral hemodynamics and metabolism after carotid stenting in
      patients unfit for major surgery].
AB  - There is increasing evidence that stenting is a useful strategy for internal
      carotid artery (ICA) stenosis in patients unfit for drastic surgery. However, it
      should be remembered that perioperative complications including seizure or
      intracerebral hemorrhage due to hyperperfusion are not so rare. The authors
      describe a case with severe ICA stenosis, who successfully underwent stenting as
      a result of intensive medical care for postoperative hyperperfusion. A 77-year
      old man with a recent history of angina pectoris and transient ischemic attack
      was referred to our hospital. Cerebral angiography showed subtotal occlusion of
      the left ICA. SPECT/PET studies revealed a disturbed reactivity to acetazolamide
      and an increase in regional oxygen extraction fraction in the left hemisphere,
      suggesting a marked reduction in cerebral perfusion pressure. He successfully
      underwent carotid stenting. Intraoperative near-infrared monitoring showed an
      increase in the concentration of total and oxidized hemoglobin in the left
      frontal area after stenting. A SPECT study just after stenting also demonstrated
      hyperperfusion in the left middle cerebral artery territory. His blood pressure
      was carefully controlled to avoid "hyperperfusion syndrome" including headache,
      seizure and intracerebral hemorrhage. Follow-up SPECT/PET studies showed a
      normalization of hemodynamic and metabolic parameters. SPECT/PET studies are
      quite valuable to predict and prevent hyperperfusion syndrome after carotid
      stenting, and result in good clinical outcome.

PMID- 14719447
TI  - [Usefulness of intravascular ultrasound in embolization of dural arteriovenous
      fistula: a case report].
AB  - A 66-year-old male was admitted with right homonymous hemianopsia. Angiograms
      revealed a dural arteriovenous fistula (DAVF) involving the left transverse
      sigmiod sinus. The DAVF was fed by the left occipital, middle meningeal, and
      posterior auricular arteries and drained into the left transverse sinus with
      occlusion of the left internal jugular vein and reversed flow of the left
      occipital cortical veins. Positron emission tomography (PET) study showed
      decreased regional cerebral blood flow (rCBF), regional oxygen extraction
      fraction (rOEF) and regional cerebral metabolic rate of oxygen (rCMRO2) and
      increased regional cerebral blood volume (rCBV). The patient was treated by
      transarterial and transvenous embolization. Before transvenous embolization, we
      attempted to observe the perisinus structure used by intravascular ultrasound
      (IVUS). IVUS was able to demonstrate multiple channels formed by DAVF and
      transvenous embolization was performed accurately at the exact fistulous site.
      After treatment, the DAVF had completely disappeared but clinical symptom had
      hardly any changed. A PET study showed that the rCBF and rCBV were normalized but
      rOEF and rCMRO2 had not changed. Eight months after treatment, PET study showed
      some normalization of rOEF and rCMRO2 of the left occipital lobe with the
      clinical symptom. IVUS is useful in determining the exact sites of transvenous
      embolization of DAVF.

PMID- 14719448
TI  - [Ictal monitoring of epileptic seizures: basic knowledge of clinical nerve
      physiology for neurosurgeons].

PMID- 14719449
TI  - [The outline of stereotactic brain operations: a guide to stereotactic brain
      operations].

PMID- 14719450
TI  - [Clinical study of endocrine therapy in stage B and C prostate cancer].
AB  - To evaluate the usefulness of endocrine therapy for stage B and C prostate
      cancer, we carried out a retrospective study on overall survival rate, cause
      specific survival, PSA recurrence-free rate, and their predictive factors in 118
      patients with stage B prostate cancer, 61 with stage C prostate cancer who
      underwent endocrine therapy at our department between 1985 and 2001. The cause
      specific survival rate and PSA recurrence-free rate of stage B patients who
      underwent endocrine therapy were well, and they will take a good clinical course.
      Thus, in this stage of prostate cancer, aged patients and patients with
      complications may be good candidates for endocrine therapy. The cause-specific
      survival rate and PSA recurrence-free rate in the stage C patients who underwent
      endocrine therapy were significantly low. In stage C patients, endocrine therapy
      should be combined early with other methods such as radiotherapy. In the stage B
      patients who underwent endocrine therapy, PSA and Gleason score appeared to be
      associated with the cause-specific survival rate and PSA recurrence-free rate.

PMID- 14719451
TI  - [Urethral stent (Memotherm) for the treatment of benign prostatic hyperplasia].
AB  - We used a urethral stent for management of high-age and high-risk patients with
      benign prostatic hyperplasia (BPH) who needed surgical therapy. Nine patients
      were treated by this method. Chief complaints were urinary retention in 6
      patients, dysuria with much residual urine in 2 and dysuria in 1. Blood loss and
      complications of the method were minimal. Postoperatively, 8 of the patients were
      able to void and on the average, residual urine of the patients was approximately
      10 ml. Implantation of the urethral stent is a safe and non-invasive therapy for
      the patients who are unsuitable for invasive therapy.

PMID- 14719452
TI  - Proliferative status is a risk index for recurrence in primary superficial
      (pTa/T1) low-grade urothelial bladder carcinoma.
AB  - The current clinicopathologic study for evaluation of superficial bladder cancer
      still has limitations in predicting the true behavior of recurrence. To determine
      the high-risk recurrence factors, we studied the influence of Ki-67, c-erbB-2,
      p53 and multidrug resistance-associated protein (MRP) expression. Samples were
      obtained from 33 pTa and 46pT1 diagnosed bladder cancer patients with a mean
      follow-up of 48.7 +/- 30.6 months. The contingency table method, Kaplan-Meier
      curve and multivariate analysis were used to evaluate the association among the
      immunohistochemical factors expression, clinicopathologic parameters with tumor
      recurrence. Stage pT1 tumors, sessile tumors and large tumors (> 3 cm) showed a
      significantly high recurrence rate (p = 0.0158, p = 0.0162, p = 0.0001
      respectively). Tumors with overexpression of Ki-67, c-erbB-2 and p53 were more
      likely to recur (p = 0.0035, p = 0.0027, p = 0.0076 respectively), MRP expression
      was not associated with recurrence. Multivariate analysis showed that large
      tumors and high Ki-67 expression were independent indicators of recurrence. On
      the other hand, in tumors less than 1 cm, recurrence was significantly correlated
      with overexpression of Ki-67 and p53. High Ki-67 expression could discriminate
      higher recurrence cases in grade 2, pT1 and single tumors. The c-erbB-2
      overexpression was more frequently associated with recurrence in sessile tumors,
      large tumors, multiple and grade 1 tumors. The p53 overexpression also predicted
      a higher risk of recurrence in pTa tumors. These data demonstrated that the use
      of proliferative related proteins yields significant prognostic information in
      addition to clinicopathological factors, high Ki-67 expression is a reliable
      indicator of recurrence. A combination rather than any factor alone could more
      accurately predict tumor recurrence.

PMID- 14719453
TI  - [Vesical actinomycosis: a case report].
AB  - A 55-year-old woman had complained of lower abdominal pain for 5 years. A
      computed tomographic CT scan and magnetic resonance imaging revealed a
      heterogeneous density mass on the left side of the bladder. CT-guided needle
      biopsy showed only inflammatory cell infiltration without histological diagnosis.
      To confirm the diagnosis, the mass was resected together with part of the bladder
      and peritoneum. On the cut surface, the mass was centrally pale yellow and
      adherent to the thickened hard wall of the bladder and peritoneum. Pathological
      diagnosis was chronic granulomatous inflammation with actinomycosis. This is, to
      our knowledge, the 12th case report of vesical actinomycosis in Japan. Although
      actinomycosis is very rare in urological field, abdominal actinomycosis should be
      considered as the differential diagnosis of any inflammatory abdominal mass.

PMID- 14719454
TI  - [Laparoscopic pyeloplasty for a secondary ureteropelvic junction obstruction
      after renal trauma: a case report].
AB  - We report a case of secondary ureteropelvic junction obstruction due to renal
      trauma treated by laparoscopic pyeloplasty. A 25-year-old man, who had renal
      trauma due to a traffic accident, complained of left lumbago and was diagnosed
      with left ureteropelvic junction obstruction. Endoscopic balloon dilation was
      performed twice, but the hydronephrosis did not change. Subsequently,
      laparoscopic pyeloplasty was performed with no complications. After operation,
      lumbago disappeared and hydronephrosis and renal function improved. Secondary
      ureteropelvic junction obstruction is rare, and this case seems to be the first
      case managed by laparoscopy in Japan.

PMID- 14719455
TI  - [Myelolipoma of the adrenal gland presenting as upper abdominal symptoms: a case
      report].
AB  - A case of adrenal myelolipoma is presented. A 39-year-old woman was admitted to
      our hospital for further examination of a right adrenal mass, which was found by
      examination for nausea, vomiting and upper abdominal pain. Imaging analyses by
      computed tomography and magnetic resonance imaging revealed a round fatty mass.
      Endocrine study of the adrenal gland showed normal results. Right adrenalectomy
      was performed. The tumor weighed 240 g and the histological diagnosis was adrenal
      myelolipoma. Postoperative course was uneventful and upper abdominal symptoms
      disappeared after surgery.

PMID- 14719456
TI  - [Leiomyoma of the urinary bladder: report of three cases].
AB  - We report 3 cases of leiomyoma of the urinary bladder. One patient was a 57-year
      old female. Magnetic resonance imaging (MRI) revealed a small tumor, and
      cystoscopy revealed a submucosal tumor on the left wall. Partial cystectomy was
      performed, and she has had no recurrence for 10 months. Two females who were aged
      68 years and 52 years, were referred to our hospital with the complaint of pain
      of meatus of urethra, and pollakisuria, respectively. Transurethral resection of
      bladder tumor (TURBT) was performed, and they have had no recurrence for more
      than 3 and 4 years, respectively. Histological examination in the three cases
      showed a leiomyoma of the urinary bladder. To our knowledge, there are 151 cases
      of leiomyoma of the urinary bladder reported in the literature in Japan.

PMID- 14719457
TI  - [Testicular malignant lymphoma: a case report].
AB  - We report a case of malignant lymphoma arising from the testicle in a patient who
      had been on chemotherapy for a long period after orchiectomy. A 54-year-old male
      presented with indolent swelling in the right scrotum. Diagnosed as having a
      testicular tumor by ultrasonography and MRI, he underwent orchiectomy. According
      to the histopathological diagnosis, the tumor was classified as non-Hodgkin's
      lymphoma, diffuse large cell type, B cell type. Diagnosis of Stage I eA was made
      by the Arr Arbor classification. Four courses of cycrophosphamide, adriamycin,
      vincristin and prednisolone (CHOP) therapy were administered. COP (CHOP minus
      adriamycin) therapy has been given every four months on an out-patient basis. At
      present, 28 months after the operation, no evident recurrence has been found.

PMID- 14719458
TI  - [Traumatic rupture of giant hydronephrosis due to ureteral stone: a case report].
AB  - A case of rupture of giant hydronephrosis due to blunt trauma is reported. A 49
      year-old male was admitted to our hospital complaining of right flank pain and
      gross hematuria after falling from a roof. Radiological evaluation lead to the
      diagnosis of marked right hydronephrosis with severe parenchymal thinning
      secondary to ureteral stone, left staghorn calculus and the rupture of right
      kidney. Right nephrectomy was performed and the postoperative course was
      uneventful. Three weeks later, percutaneous nephrolithotomy (PNL) was performed
      for left staghorn calculus. Other articles concerning giant hydronephrosis
      discovered following trauma are reviewed.

PMID- 14719459
TI  - Inguinal herniation in two patients with continuous ambulatory peritoneal
      dialysis.
AB  - We report two cases of subacute inguinal swelling in uremic patients on
      continuous ambulatory peritoneal dialysis (CAPD). Computed tomography,
      scintigraphy demonstrated a mass in the right groin. Surgical repair of an
      inguinal hernia resulted in complete resolution of the inguinal swelling. Both
      patients could restart continuous ambulatory peritoneal dialysis, without
      complication.

PMID- 14719460
TI  - Efficacy of prophylactic and therapeutic human immunoglobulin on West Nile virus
      infection.

PMID- 14719461
TI  - Lipid oxidation kinetics in hemodialysis patients with and without history of
      myocardial infarction.
AB  - BACKGROUND: In lipid oxidation kinetics studies, prevalent cardiovascular disease
      has been associated with shortened lag phase, the length of time preceding the
      onset of oxidation. OBJECTIVES: To examine, in vitro, copper-induced lipid
      oxidation kinetics in unfractionated serum from hemodialysis patients and to
      determine differences in kinetic parameters between patients with and without a
      history of CVD. METHODS: Of the 76 patients enrolled in a study of oxidative
      stress in hemodialysis (44/76 with prevalent CVD, 53/76 males), 9 males with a
      history of myocardial infarction were selected and matched for age, diabetes and
      smoking status with 9 males from the non-CVD group. The kinetics of lipid
      oxidation was studied. Blood chemistry determinations including serum lipids,
      lipoproteins, hemostatic factors and serum malondialdehyde were obtained.
      Variables were compared using the t-test for independent samples with history of
      MI entered as the categorical variable. RESULTS: Tmax, the oxidation kinetic
      parameter defined as the time at which the rate of absorbing product accumulation
      was maximal, was significantly shorter in dialysis patients with a history of MI
      than in those without (115.2 +/- 38.5 vs. 162.7 +/- 48.9 minutes, P = 0.04).
      Further, Tmax and MDA were negatively correlated to one another (r = -0.47, P =
      0.04). Odds ratios indicate that each 1 minute increase in Tmax was associated
      with a 3% decrease in odds that a subject had a history of MI. CONCLUSIONS: These
      findings indicate the presence of increased oxidative stress in hemodialysis
      patients with a history of MI.

PMID- 14719462
TI  - Risk factor profile and achievement of treatment goals among hypertensive
      patients in general practice in Israel: baseline results from the Israeli Blood
      Pressure Control (IBPC) program.
AB  - BACKGROUND: The Israeli Blood Pressure Control program was initiated to enhance
      the control of modifiable risk factors among high risk hypertensive patients
      followed by general practitioners in Israel. OBJECTIVE: To report the baseline
      results of the state of the treatment regarding blood pressure management, lipid
      and glucose control as well as obesity and smoking cessation among the patients.
      METHODS: Hypertensive patients were screened in 30 general practice clinics
      supervised by family medicine specialists seeing 1,000-5,000 patients each.
      Between 50 and 250 hypertensive patints were diagnosed at each participating
      clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well
      as target organ damage and medications were recorded for all patients. RESULTS:
      Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 +/-
      12. Blood pressure control was achieved in only 33.1% of total hypertensive
      patients. Low density lipoprotein control was achieved in 31.1% of all patients,
      and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl);
      20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of
      patients 38.9% were obese (BMI > 30 kg/m2). While there were more obese females
      than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or
      glucose control between the genders. CONCLUSION: Risk factor management of
      hypertensive patients attending general practice clinics in Israel is not
      optimal, especially among those with diabetes or in need of secondary prevention
      measures. A long-term intervention program for high risk patients in the
      community is needed to improve the current situation.

PMID- 14719463
TI  - Cardiovascular diseases in patients with high levels of plasma high density
      lipoprotein: association with increased plasma oxidative state.
AB  - BACKGROUND: Increased levels of high density lipoprotein (over 60 mg/dl) are
      considered to be a negative risk factor for ischemic heart disease. However, some
      patients with high HDL still develop cardiovascular diseases. OBJECTIVE: To
      explore why patients with very high HDL still suffer from cardiovascular
      diseases. METHODS: We analyzed several risk factors, such as increased lipid
      peroxidation, hyperhomocysteinemia and increased release of inflammatory
      molecules, that could be related to the development of vascular disease in
      patients with high serum HDL levels. Patients with HDL cholesterol levels above
      75 mg/dl were selected for this study and were separated into two groups based on
      the presence of atherosclerotic vascular disease, i.e., those with vascular
      disease (patients) and those without (controls). RESULTS: Plasma isolated from
      the patient group exhibited significantly increased lipid peroxidation by 21% and
      decreased total antioxidant status by 17%, but there were no differences
      regarding their serum or their paraoxonase activity. Moreover, both groups
      exhibited similar levels of serum C-reactive protein, fibrinogen and
      homocysteine, enabling us to eliminate these risk factors in the etiology of
      cardiovascular disease in the patient group. CONCLUSION: Increased oxidative
      stress could be one of the factors leading to cardiovascular diseases in patients
      with high serum HDL levels.

PMID- 14719464
TI  - Influenza vaccination: reduction in hospitalizations and death rates among
      members of "Maccabi Healthcare Services" during the 2000-2001 influenza season.
AB  - BACKGROUND: Upper respiratory tract illnesses have been associated with an
      increased risk of morbidity and mortality. OBJECTIVE: To assess the influence of
      vaccination against influenza on the risk of hospitalization in internal medicine
      and geriatric wards, and the risk of death from all causes during the 2000-2001
      influenza season. METHODS: A historical cohort study was conducted using
      computerized general practitioner records on patients aged 65 years and above,
      members of "Maccabi Healthcare Services"--the second largest health maintenance
      organization in Israel with 1.6 million members. The patients were divided into
      high and low risk groups corresponding to coexisting conditions, and were
      studied. Administrative and clinical data were used to evaluate outcomes.
      RESULTS: Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline,
      vaccinated subjects were sicker and had higher rates of coexisting conditions
      than unvaccinated subjects. Vaccination against influenza was associated with a
      30% reduction in hospitalization rates and 70% in mortality rates in the high
      risk group. The NNT (number needed to treat) measured to prevent one
      hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk
      group). When referring to length of hospitalization, one vaccine was needed to
      prevent 1 day of hospitalization among the high risk group. Analyses according to
      age and the presence or absence of major medical conditions at baseline revealed
      similar findings across all subgroups. CONCLUSIONS: In the elderly, vaccination
      against influenza is associated with a reduction in both the total risk of
      hospitalization and in the risk of death from all causes during the influenza
      season. These findings compel the rationale to increase compliance with
      recommendations for annual influenza vaccination among the elderly.

PMID- 14719465
TI  - Total hip arthroplasty in patients younger than 30 years of age.
AB  - BACKGROUND: Previously reported results of total hip arthroplasty in patients
      under the age of 30 indicate a high complication rate and questionable
      durability. OBJECTIVES: To estimate the results of THA in extremely young
      patients. METHODS: We report the results of 69 THA procedures in 56 patients who
      were under the age of 30 at the time of surgery (mean age 23.23 +/- 4.31 years)
      and were followed postoperatively for 2-23 years (mean 7.4 +/- 3.79 years).
      RESULTS: Loosening of the cup (11/69) and early traumatic dislocation (5/69)
      accounted for the majority of complications. CONCLUSION: The final average Harris
      hip scores of 90.59 +/- 9.36 in these patients indicated that THA is a successful
      and durable treatment modality for young patients with disabling diseases
      affecting the hip joint. However, due to the likelihood of complications it
      should be used with caution in this patient group. Efforts should be made to
      diminish the complication rate.

PMID- 14719466
TI  - Cardiac surgery in octogenarians--a better prognosis in coronary artery disease.
AB  - BACKGROUND: Cardiac surgery is being performed with increasing frequency in
      patients aged 80 years and older. OBJECTIVES: To examine the long and short-term
      results of surgery in this age group. METHODS: We retrospectively investigated
      202 consecutive patients aged 80 years or older who underwent cardiac surgery
      between 1991 and 1999, Ninety-six operations (48%) were urgent. RESULTS: The
      study group comprised 140 men (69%) and 62 women (31%) with a mean age of 82.1
      years (range 80-89). Preoperatively, 120 patients (59%) had unstable angina, 37
      (18%) had left main coronary artery disease, 22 (11%) had renal failure, 17
      (8.5%) had a history of stroke and 13 (6.5%) had previous cardiac surgery.
      Hospital mortality for the whole group was 7.4%. Postoperative complications
      included: re-exploration for bleeding in 15 (7.4%), stroke in 8 (4%), sternal
      wound infection in 3 (1.5%), low cardiac output in 17 (8.4%), new Q wave
      myocardial infarction in 5 (2.5%), renal failure in 17 (8.5%), and atrial
      fibrillation in 71 (35%). The actuarial survival for patients discharged from the
      hospital was 66% at 5 years and 46% at 8 years. The type of surgical procedure
      was significantly associated with increased early mortality (coronary artery
      bypass grafting only in 2.9%, CABG + valve in 16.1%, valve only in 16.7%; P =
      0.01). Significant predictors (P < 0.05) for late mortality included type of
      surgical procedure, congestive heart failure, and postoperative low cardiac
      output. CONCLUSIONS: When appropriately applied in selected octogenarians,
      cardiac surgery can be performed with acceptable mortality and good long-term
      results.

PMID- 14719467
TI  - A topical skin protectant against chemical warfare agents.
AB  - BACKGROUND: Sulfur mustard and VX are potent chemical warfare agents that
      penetrate rapidly through the skin, causing severe prolonged injuries and
      sometimes death. OBJECTIVES: To develop a topically applied pretreatment that
      will act as a barrier and prevent the absorption of these agents through the
      skin, reducing morbidity and saving life. METHODS: Several formulations were
      developed and tested in preclinical animal studies in pigs. The protecting cream
      was applied as a single application (0.5-1 ml/100 cm2) prior to exposure (10
      minutes to 12 hours) to sulfur mustard or VX. Assessment of sulfur mustard
      induced skin damage was based on clinical and histologic evaluations. When tested
      against VX, clinical signs and blood cholinesterase activity were monitored. At
      the final stage of development, safety studies were conducted in animals and in
      human volunteers. RESULTS: The formulation that gave the best results, coded IB1
      (under patent application), provided significant protection against a 1 hour
      exposure to sulfur mustard (droplets or vapor). All the pigs pretreated with IB1
      cream survived a 1-4 hour challenge of 2xLD50 VX and did not exhibit any overt
      clinical signs. Protection was exhibited even when the cream was applied 12 hours
      (single application) prior to exposure. IB1 was found to be non-irritating in
      animals and humans. No adverse effects were found in a Phase I clinical study in
      young healthy volunteers when the cream was applied to around 20% of the skin
      surface (results presented elsewhere). CONCLUSIONS: IB1 cream has been shown to
      be a safe and effective topical skin protectant against the chemical warfare
      agents sulfur mustard and VX.

PMID- 14719468
TI  - Phobic postural vertigo: a new proposed entity.
AB  - BACKGROUND: Dizziness and vertigo can be a complaint in various psychiatric
      conditions where it usually constitutes only one of the features of the syndrome.
      Lately, a somatoform disorder characterized by almost mono-symptomatic dizziness
      and unsteadiness has been described. Since phobic postural vertigo usually
      presents without anxiety or other psychological symptomatology, patients with
      this condition seek help at neurologic and otolaryngologic clinics where they are
      often misdiagnosed as suffering from organic vertigo. OBJECTIVES: To present the
      clinical features of 55 consecutive patients diagnosed with phobic postural
      vertigo at our clinic during 1998-2002. METHODS: We conducted a retrospective
      review of patients' medical records and report two typical cases for
      illustration. RESULTS: The patients presented with complaints of unsteadiness
      with or without dizziness, and attacks of sudden veering that caused them to
      grasp for support. Accompanying anxiety was admitted by only 5% and vegetative
      symptoms were reported in 18%. In 16% the symptoms resulted in avoidance
      behavior. A stressful life event or an unrelated somatic disease triggered the
      onset of PPV in 35% of patients, whereas a vestibular insult preceded the
      symptoms in 13%. The mean duration of symptoms was 26.7 +/- 39.1 months (range
      0.5-20 years). In 72% of patients the symptoms resolved after the psychological
      mechanism of their symptoms was explained to them; 24% improved with
      antidepressant treatment (selective serotonin reuptake inhibitors or tricyclic
      antidepressants), and only in 4% did the symptoms persist. CONCLUSIONS: Since PPV
      is a frequently encountered diagnosis at some specialized dizziness clinics,
      familiarity with this entity resulting in early diagnosis can avoid unnecessary
      examinations and lead to effective treatment.

PMID- 14719469
TI  - Endothelial dysfunction in preeclampsia and eclampsia: current etiology and
      future non-invasive assessment.

PMID- 14719470
TI  - Surgery for tremor.
AB  - Tremor is extremely common and often functionally disabling. When tremor becomes
      medically intractable, surgery is a good and safe option for appropriate
      candidates. Both stereotactic thalamotomy and thalamic deep brain stimulation by
      means of an implanted electrode offer very high rates of success with an
      acceptably low complication rate.

PMID- 14719471
TI  - Therapeutic alternatives for symptomatic intracranial atherosclerotic disease.

PMID- 14719472
TI  - Lipid peroxidation and atherosclerosis: the importance of selected patient group
      analysis.

PMID- 14719473
TI  - Endothelial dysfunction: a crystal ball prediction for enhanced cardiovascular
      risk?

PMID- 14719474
TI  - Periodic fever in infants: familial Mediterranean fever only?

PMID- 14719476
TI  - Infantile familial Mediterranean fever.

PMID- 14719475
TI  - Analysis of polymorphic patterns in candidate genes in Israeli patients with
      prostate cancer.
AB  - BACKGROUND: The precise genes involved in conferring prostate cancer risk in
      sporadic and familial cases are not fully known. OBJECTIVES: To evaluate the
      genetic profile within several candidate genes of unselected prostate cancer
      cases and to correlate this profile with disease parameters. METHODS: Jewish
      Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms
      within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and
      HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and
      pathologic parameters. RESULTS: The EPHX gene His113 allele was detected in 21.4%
      (33/154) of patients in whom disease was diagnosed above 61 years, compared with
      5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset
      disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared
      with 18% (34/188) with grade II and up (P = 0.004). All other tested
      polymorphisms were not associated with a distinct clinical or pathologic feature
      in a statistically significant manner. CONCLUSIONS: In Israeli prostate cancer
      patients, the EPHX His113 allele is seemingly associated with a more advanced,
      late-onset disease. These preliminary data need to be confirmed by a larger and
      more ethnically diverse study.

PMID- 14719477
TI  - Excacerbation of heart failure after discontinuation of long-term left
      ventricular pacing: resolution after cardiac resynchronization therapy.

PMID- 14719478
TI  - Sepsis-like syndrome caused by the Russian medication pyrogenal (Salmonella typhi
      endotoxin).

PMID- 14719479
TI  - Multiple life-threatening fainting episodes: fatal systemic mastocytosis.

PMID- 14719480
TI  - Nitrofurantoin-induced pancreatitis.

PMID- 14719481
TI  - Extensive diverticulosis of the small intestine.

PMID- 14719482
TI  - Postnatal diagnosis of severe hemolytic disease of the newborn due to minor blood
      group antibodies anti-E and anti-C.

PMID- 14719483
TI  - Diuretics vs. ACE inhibitors.

PMID- 14719484
TI  - Legal and human rights challenges for people living with HIV/AIDS: a personal
      perspective.

PMID- 14719485
TI  - The 1st Annual Awards for Action on HIV/AIDS and Human Rights.
AB  - The 1st Annual Awards for Action on HIV/AIDS and Human Rights were awarded to the
      Vancouver Area Network of Drug Users and to Dr. Wan Yanhai, a Chinese physician
      and activist. The international attention and media coverage of the awards was
      heightened by the fact that the Chinese government had detained Dr. Wan for
      disclosing information about unsanitary blood collection practices in Henan
      province. An international outcry led to Dr. Wan's release on 20 September 2002.

PMID- 14719486
TI  - House of Commons committee releases report on Canada's drug strategy.
AB  - On 17 May 2001, the House of Commons created a Special Committee on Non-Medical
      Use of Drugs based on a motion introduced by Randy White, Canadian Alliance MP
      (Langley-Abbottsford) and gave it a very broad mandate to study "the factors
      underlying or relating to the non-medical use of drugs in Canada" and to propose
      recommendations aimed at reducing "the dimensions of the problem involved in such
      use." In December 2002, the Committee released its report, entitled Policy for
      the New Millennium: Working Together to Redefine Canada's Drug Strategy. The
      report contains many good recommendations, but fails to deal adequately with the
      fundamental harms caused by Canada's drug laws and federal government inaction.
      Far better is the supplementary report written by NDP MP Libby Davies (Vancouver
      East), which contains an excellent, informed critique of the report. The
      supplementary report from the official opposition, written by MPs Randy White and
      Kevin Sorenson (Crowfoot, Alberta) also makes for interesting, if troubling,
      reading--it is based nearly exclusively on fiction rather than facts and science.

PMID- 14719487
TI  - HIV/AIDS in prisons: recent developments.
AB  - In a report released on 20 November 2002, entitled Action on HIV/AIDS in Prisons:
      Too Little, Too Late--A Report Card, the Canadian HIV/AIDS Legal Network
      concluded that despite repeated studies and nearly ten years of recommendations
      for urgent and pragmatic action, the response of Canadian governments to
      HIV/AIDS, HCV, and injection drug use in prisons remains inadequate. Only a few
      weeks later, the House of Commons Special Committee on Non-Medical Use of Drugs
      released its report, which contained a number of recommendations to the
      Correctional Service of Canada. Although the Committee avoided talking about
      needle exchange programs in prisons, it did recommend them! Meanwhile, in
      Ireland, not even condoms or bleach are provided.

PMID- 14719488
TI  - Canada refuses to issue a visa to an HIV-positive worker on antiretroviral drugs.
AB  - Citizenship and Immigration Canada has denied an application for a visa from an
      HIV-positive man even though he is in good health. The man was seeking to fill a
      two-year work term in Canada. The case raises concerns about Canada's immigration
      policies for people with HIV and about the ability of organizations working in
      AIDS to hire HIV-positive foreign workers.

PMID- 14719489
TI  - Supervised injection sites: Minister of Health ready to review applications for
      pilot research projects.
AB  - Since 1 January 2003, Health Canada has been prepared to receive proposals for
      pilot supervised injection sites (SISs). Vancouver has already indicated that it
      will submit a proposal within a few months. Other cities that have expressed an
      interest in opening SISs include Montreal, Quebec, Winnipeg, and Victoria.

PMID- 14719490
TI  - Minister reaffirms commitment to provide medical marijuana, but delays continue.
AB  - Amid ongoing doubts about the federal government's commitment to provide
      marijuana for medical use, the first Canadian clinical trial of smoked cannabis
      has been launched, and a Senate committee has released its controversial and much
      anticipated report.

PMID- 14719491
TI  - Canada will have a national HIV vaccine plan.
AB  - Health Canada announces that a national HIV vaccine plan will be developed in
      consultation with key stakeholders and that it will contribute to the global
      vaccine effort.

PMID- 14719492
TI  - Senate committee calls for major new spending on health care.
AB  - Senator Michael Kirby's committee says that the federal government should invest
      $6.5 billion more each year. It calls for the establishment of new national
      programs to pay for catastrophic drug costs and to expand home and palliative
      care.

PMID- 14719493
TI  - Provinces create centralized system for assessing new drugs.
AB  - Provincial health ministers have created a common drug-review process for
      assessing whether new drugs should be place on provincial formularies. The new
      system will save money, but will it improve access?

PMID- 14719494
TI  - Regulators deny access to experimental hepatitis C drug.
AB  - An application for access to an experimental hepatitis C drug under Canada's
      Special Access Programme has been turned down. In the process, Canada's drug
      regulators have created discomfort and uncertainty about how the Special Access
      Programme is managed.

PMID- 14719495
TI  - Medical association calls for routine HIV testing of pregnant women.
AB  - The Canadian Medical Association says that routine HIV testing of pregnant women
      is necessary because there are still babies being born with HIV infection.
      Critics respond that routine testing is the same as mandatory testing, that there
      is no reason to waive the requirement for informed consent accompanied by pre
      test counselling, and that physicians need to do a better job of offering HIV
      testing to pregnant women.

PMID- 14719496
TI  - HIV study among pregnant Aboriginal women raises concerns.
AB  - An unlinked HIV seroprevalence study among pregnant Aboriginal women in BC
      reveals an alarming trend and raises ethical questions about certain types of
      research in Aboriginal communities.

PMID- 14719497
TI  - Vancouver police raid needle exchange run by drug users.
AB  - The police claimed that drug trafficking was going on at the needle exchange run
      by the Vancouver Area Network of Drug Users, but they failed to provide any
      evidence to that effect. The police later apologized for their remarks and the
      exchange re-opened.

PMID- 14719498
TI  - Studies document gender differences in HIV risk and impact.
AB  - According to new studies, women account for half the new HIV infections in
      Aboriginal people, and women who inject drugs are at higher risk than their male
      counterparts.

PMID- 14719499
TI  - RCMP lay charges in tainted-blood scandal.

PMID- 14719500
TI  - Spitting incident leads to renewed calls for mandatory testing.

PMID- 14719501
TI  - Alberta gets a second methadone clinic.

PMID- 14719502
TI  - Youth prevented from giving out condoms at a Catholic festival.

PMID- 14719503
TI  - NWT prohibits discrimination based on gender identity.

PMID- 14719504
TI  - Chinese scholars call for AIDS rules based on respect for individual rights.
AB  - In June 2002, the UN Theme Group on HIV/AIDS in China published a comprehensive
      situation analysis and needs assessment of the HIV/AIDS epidemic in the People's
      Republic of China (PRC). The report, entitled "HIV/AIDS: China's Titanic Peril",
      also describes and analyzes current HIV/AIDS legislation and policies. It notes
      that "laws and regulations that are based on fear and prejudice have contributed
      to fuelling the epidemic instead of curbing it." The report observes that the
      targets and goals established in China's five-year Plan of Action (2001-2005) are
      not consistent with the commitments endorsed in June 2001 at the United Nations
      General Assembly Special Session on HIV/AIDS. It states that the Plan "continues
      to present HIV/AIDS as a medical problem, and fails to understand the epidemic as
      a broader development issue." Even where laws could assist, enforcement remains a
      huge challenge. For example, in 1998 the National People's Congress passed a law
      prohibiting commercial blood donations for medical purposes. Nonetheless, the
      illicit and unregulated blood trade, which has rapidly accelerated the spread of
      HIV infection in China, has continued. When the alarm was sounded by Dr. Wan
      Yanhai, coordinator of the AIZHI (AIDS) Action Project, the government response
      was to arrest him. In the following article, Nick Young, editor of China
      Development Brief, reviews the findings of three studies commissioned by the
      United Nations Development Programme (UNDP) on the role of the law in response to
      HIV/AIDS.

PMID- 14719505
TI  - ILO training for industrial court judges.
AB  - In this article Jane Hodges, Senior Labour Law Specialist, International Labour
      Office, examines the role of the International Labour Organization in improving
      the response of the labour court system to the challenges of HIV/AIDS.

PMID- 14719506
TI  - HIV/AIDS and health at the World Summit on Sustainable Development.

PMID- 14719507
TI  - What is the physiological function of mast cells?
AB  - Under physiological conditions, skin mast cells preferentially localize around
      nerves, blood vessels and hair follicles. This observation, which dates back to
      Paul Ehrlich, intuitively suggests that these enigmatic, multifacetted
      protagonists of natural immunity are functionally relevant to many more aspects
      of tissue physiology than just to the generation of inflammatory and vasodilatory
      responses to IgE-dependent environmental antigens. And yet, for decades,
      mainstream-mast cell research has been dominated by a focus on the -undisputedly
      prominent and important - mast cell functions in type I immune responses and in
      the pathogenesis and management of allergic diseases. Certainly, it is hard to
      believe that the very large and rather selectively distributed number of mast
      cells in normal, uninflamed, non-infected, non-traumatized mammalian skin or
      mucosal tissue simply hanging around there lazily day and night, just wait for
      the odd allergen or parasite-associated antigen to come by so the mast cell can
      finally swing into action. Indeed, the past decade has witnessed a renaissance of
      mast cell research 'beyond allergy', along with a more systematic exploration of
      the surprisingly wide range of physiological functions that mast cells may be
      involved in. The current debate sketches many exciting horizons that have
      recently come into our vision during this intriguing, ongoing search.

PMID- 14719508
TI  - Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX
      2 adn iNOS inhibitors for treatment in Malaysia.
AB  - BACKGROUND: Promising new pharmacological agents and gene therapy targeting
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could
      modulate treatment of colorectal cancer in the future. The aim of this study was
      to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in
      colorectal cancer specimens in Malaysia. This is a useful prelude to future
      studies investigating interventions directed towards COX-2 adn iNOS. METHODS: A
      cross-section study using retrospective data over a 2-year period (1999-2000)
      involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of
      colorectal cancers that were surgically resected in a tertiary referral. RESULTS:
      COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and
      in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101,
      81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue.
      Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly
      differentiated tumours had significantly lower total beta-catenin (p = 0.009) and
      COX-2 scores (p = 0.031). No significant relationships were established between
      pathological stage and beta-catenin, COX-2 and iNOS scores. CONCLUSIONS: the
      accumulation of beta-catenin does not seem to be sufficient to activate pathways
      that lead to increased COX-2 and iNOS expression. A high proportion of colorectal
      cancers were found to express COX-2 and a significant number produced iNOS,
      suggesting that their inhibitors may be potentially useful as chemotherapeutic
      agents in the management of colorectal cancer.

PMID- 14719509
TI  - Validating the use of rectus muscle fragment welding to control presacral
      bleeding during rectal mobilization.
AB  - The incidence of presacral bleeding during rectal mobilization is low, but such
      bleeding may be massive and even fatal. Haemostasis can be difficult to achieve
      using conventional methods because of the complex interlacing of the venous
      network at the sacral periosteum. Historically, pelvic packing and metallic
      thumbtacks have been the more commonly used methods in our institution. However,
      the need for repeat surgery to remove the packs and the difficulties encountered
      in tack application have forced us to explore other methods. In 1994, the
      procedure termed muscle fragment welding, which uses electrocautery through a
      rectum muscle fragment, was introduced to control presacral bleeding. From
      January 1999 to February 2002, six of 416 patients undergoing pelvic surgery in
      our institution developed massive presacral haemorrhage and therefore, this
      technique was used. Haemostasis was immediate and permanent. No major untoward
      postoperative events such as re-bleeding or infection were noted. One cas
      developed a second-degree burn in the right elbow due to a misplaced ground
      conduction plate. Rectus muscle fragment welding is , in our experience, an
      effective and practical method of controlling presacral haemorrhage.

PMID- 14719510
TI  - Antrochoanal polyps: clinical presentation and the role of powered endoscopic
      polypectomy.
AB  - Antrochoanal polyps are a rare clinical entity. In this review of patients
      treated between January 1996 and September 2002, there were 18 cases of
      antrochoanal polyps. The mean age of patients was 20 years. Nasal obstruction was
      the most common symptom (17 cases, 94%), followed by rhinorrhoea (44%), epistaxis
      (33%), postnasal drip (28%), and snoring (22%). Chronic sinus was the most common
      associated rhinological finding (50%). Various surgical approaches were used:
      endoscopic polypectomy and middle meatal antrostomy in seven patients (38.9%),
      endoscopic polypectomy and inferior meatal antrostomy in three patients (16.7%)
      and Caldwell-Luc surgery in one patient (5.6%). No complications were noted in
      patients treated with powered instrumentation, including the three patients in
      whom combined transcanine approaches were used. We concluded that powered
      endoscopic polypectomy was safe and effective. It allowed a more complete
      dissection and may diminish the chance of recurrence.

PMID- 14719511
TI  - Appropriateness of colonoscopy in a tertiary referral centre.
AB  - The aim of this study was to determine the appropriateness of colonoscopy in
      relation to its diagnostic yield, with reference to the guidelines set by the
      American Society of Gastrointestinal Endoscopy (ASGE). A prospective 90-day audit
      was performed at Hospital Kualal Lumpur, which is a tertiary referral centre in
      Malaysia, to examine the appropriateness of colonoscopy by indication. During
      that time, 257 colonoscopies were performed in 244 patients. The predominant
      indications for colonoscopy were altered bowl habit (37%) and rectal bleeding
      (18%). Of the 257 colonoscopies, 216 (84%) were judged to be appropriate by ASGE
      guidelines. Only 43% of all colonoscopies had positive findings. Positive
      findings were found in 93% of cases judged appropriate compared with only 7%
      found in cases deemed inappropriate. There were statistically significant
      relationships between appropriateness and overall positive yield and between
      appropriateness and neoplastic findings (p < 0.05). Colonoscopy performed for
      appropriate indications yield more significant findings, this, we advocate the
      use of accepted guidelines to maintain or improve the standard colonoscopy
      services.

PMID- 14719512
TI  - Management of acute bleeding per rectum.
AB  - BACKGROUND: Bleeding per rectum is a common indication for acute hospital
      admissions to the colorectal department. The frequencies of aetiologies in
      Singapore are different from those in Western populations. A retrospective
      analysis of the demography, pathology and management of acute bleeding per rectum
      was performed to determine the outcome and difference in aetiology from the West.
      METHODS: During the 1-year period from 1 October 1995 to 30 September 1996, 547
      patients were admitted to Singapore General Hospital form the emergency
      department for acute bleeding per rectum. There were 377 males and 170 females;
      the mean age was 42 years (range, 15-97 years). RESULTS: Of the patients
      admitted, 87% wer admitted due to perianal conditions diagnosed at bedside
      proctoscopy, where haemorrhoids mad up 94%. One percent bled from the upper
      gastrointestinal tract, while 12% bled from colorectal pathology. Massive
      bleeding form the colorectum was uncommon. Less than one third of the 47 patients
      required blood transfusions. Colonoscopy was the most useful diagnostic tool for
      bleeding from the colorectum. The more common colonic pathologies were
      diverticular disease (33%), adenomas (18%), and malignancy (26%), accounting for
      the majority of acute patient admissions. Colonic causes of bleeding were less
      common and were most stable. There were differences in the frequencies of
      aetiologies in our population compared ot Western populations. Understanding the
      common pathologies and outcomes guides the management fo our patients.

PMID- 14719513
TI  - How useful is glucose detection in diagnosing cerebrospinal fluid leak? The
      rational use of CT and Beta-2 transferrin assay in detection of cerebrospinal
      fluid fistula.
AB  - BACKGROUND: This report describes the sensitivity and specificity of glucose
      detection using Glucostix test strips and computed tomography (CT) of the skull
      base for confirming cerebrospinal fluid (CSF) fistulae in patients with
      persistent rhinorrhoea or otorrhoea, and comparing them with the beta-2
      transferrin assay as the gold standard for CSF detection. METHODS: Fluid samples
      from the nose were collected from 18 patients with suspected CSF fistulae. The
      samples were assayed for beta-2 transferrin using the Western blotting and
      immunostaining technique. CT (5mm axial slice) of the skull base was performed
      for evidence of skull base fracture. The glucose levels and Glucostix results
      were compared. RESULTS: Out of the 18 samples, 15 were positive for beta-2
      transferrin adn the leaks were validated surgically in 10 patients. Give leaks
      healed spontaneously with conservative management. Glucostix tests produced three
      false positive results from blood and nasal mucus contaminated fluid. Glucostix
      failed to detect another three CSF leaks resulting from false negative tests
      because of low CSF glucose levels. The Glucostix glucose test was nonspecific and
      insensitive compared with the beta-2 transferrin assay. CT failed to detect three
      of the 15 beta-2 transferrin-positive leaks but there were no false positive
      results. CT produced six negative results, of which three were false negatives.
      CONCLUSIONS: Glucose detection using Glucostix test strips is not recommended as
      a confirmatory test due to its lack of specificity and sensitivity. In the
      presence of a skull bas fracture on CT and a clinical CSF leak, there is no need
      for a further confirmatory test. In cases where a confirmatory test is needed,
      the beta-2 transferrin assay is the test of choice because of its high
      sensitivity and specificity.

PMID- 14719514
TI  - Neonatal ovarian cysts: management with reference to magnetic resonance imaging.
AB  - OBJECTIVE: Ultrasound (US) has been used as a tool to determine the indication
      for surgery for neonatal ovarian cysts. The purpose of this study was to
      investigate whether magnetic resonance imaging (MRI) contributes to optimal
      management. METHODS: Between 1993 and 2001, US and MRI studies were
      simultaneously performed on 13 consecutive infants younger than 2 months of age
      with ovarian cysts. The US Patterns were classified as complex or simple. Signal
      intensity (SI) of the cysts on MRI was compared with that of the liver on T1
      weighted images (T1WI) and with urine on T2-weighted images (T2WI). We assumed
      that high SI on T1WI and iso or low SI on T2WI indicated complications. RESULTS:
      There were 10 complex and three simple cysts on US. Of the 10 complex cysts, two
      had no complications at surgery or resolved spontaneously. These two cysts showed
      low SI on T1WI. Eight complex cysts showed high SI on T1WI and all were
      haemorrhagic. The US diagnosis corresponded to the MRI findings in three simple
      cysts. The sensitivity of US for haemorrhage was 80%, and that of MRI was 100%.
      CONCLUSIONS: We found that MRI was a more reliable diagnostic modality than US
      for diagnosing neonatal ovarian cysts.

PMID- 14719515
TI  - Double atresia of hindgut with ileal stenosis: a case report.
AB  - An unusual case of imperforate anus with sigmoid colonic atresia and ileal
      stenosis is described. Only six cases of imperforate anus associated with colonic
      atresia have previously been reported in Japan. The possibility of other
      alimentary obstructions should thus be considered when anorectal anomalies are
      observed.

PMID- 14719516
TI  - Double intestinal atresia in imperforate anus: a diagnostic conundrum for
      paediatric surgeons.

PMID- 14719517
TI  - Localized Castleman's disease presenting as a vascular right iliac fossa mass.
AB  - Castleman's disease is a rare lymphoproliferative disorder of unknown aetiology.
      The presentation is varied, diagnosis is difficult, and optimum management is
      still unknown. We report our experience with a case of Castleman's disease in a
      34-year old woman who presented with pallor, hepatosplenomegaly, and a right
      iliac fossa mass that was 5 cm in diameter. this was initially diagnosed as a
      soft tissue sarcoma and preoperative tumour embolization was planned before
      excision. Mesenteric arteriogram revealed that the feeder arteries arose from the
      superior mesenteric artery and embolization was aborted for fear of causing bowel
      ischaemia. On laparotomy, lymphoid enlargement was found between the leaves of
      the jejunal mesentery. The tumour was relatively avascular and the overlying
      mesenteric vessels contributed to teh duplex ultrasound and computerized
      tomography appearance of hypervascularity. The tumour with the mesentery and the
      overlying segment of jejunum was excised completely. Histopathology confirmed
      Castleman's disease. The purpose of this report is to present this rare case that
      caused a diagnostic dilemma and to review the management of this disorder.

PMID- 14719518
TI  - Peer review audit of trauma deaths in a developing country.
AB  - OBJECTIVES: Peer review of trauma deaths can be used to evaluate the efficacy of
      trauma systems. The objective of this study was to estimate teh proportion of
      preventable trauma deaths and the factors contributing to poor outcome using peer
      review in a tertiary care hospital in a developing country. METHODS: All trauma
      deaths during a 2-year period (1 January 1998 to 30 December 1998) were
      identified and registered in a computerized trauma registry, and the probability
      of survival was calculated for all patients. Summary data, including registry
      information and details of prehospital, emergency room, and definitive care, were
      provided to all members of the peer review committee 1 week before the committee
      meeting. The committee then reviewed all cases and classified each death as
      preventable, potentially preventable, or non-preventable. RESULTS AND CONCLUSION:
      A total fo 279 patients were registered in the trauma registry during the study
      period, including 18 trauma deaths. Peer review judged that six were preventable,
      seven were potentially preventable, and four were non-preventable. One patient
      was excluded because the record was not available for review. The proportion of
      preventable and potentially preventable deaths was significantly higher in our
      study than from developed countries. Of the multiple contributing factors
      identified, the most important were inadequate prehospital transfer, limited
      hospital resources, and an absence of integrated and organized trauma care. This
      study summarizes the challenges faced in trauma care in a developing country.

PMID- 14719519
TI  - Peer education in friendship cliques: prevention of adolescent smoking.
AB  - The use of the term 'peer' teacher in adolescent health education programs has
      been applied with a variety of definitions. In some programs student teachers
      have been in the same grade as those they instructed; in others, they have been
      older students teaching lower grade students. The method of selection of student
      teachers has also varied. In some programs, a popular vote of students has been
      used to choose the student teachers; in other programs, the adult teachers and
      principals have chosen the student teachers. The purpose of the program reported
      here was to conduct smoking prevention education in friendship cliques taught by
      the clique's peer leaders. The friendship cliques and their peer leaders were
      identified by a computerized algorithm analysis of responses to a friendship
      questionnaire. The curriculum focused on social skills to prevent smoking and
      consisted of 8 weeks of education during the sixth and seventh grade years of 347
      adolescents. The program evaluation compared the friendship cliques with 'model'
      students identified by school officials who taught their classmates and adult
      teachers instructing their students. The prevention rates of friendship cliques
      suggest that research studying this approach is needed. A practical means of
      identifying friendship cliques and their leaders is suggested.

PMID- 14719520
TI  - Occurrence of hydrogenosomes in the rumen ciliates Ophryoscolecidae.

PMID- 14719521
TI  - An introduction to three studies of rural elderly people: effects of religion and
      culture on health.
AB  - The paper introduces three empirical studies which relate the religious beliefs
      and practices or rural older adults from different ethnic groups to their health
      behaviors. It briefly describes the rationale for the studies and their main
      components, including their aims, study sites, study populations, methods used,
      and their principal findings. Then it discusses two primary themes which run
      through all the papers, namely rurality and cross-cultural comparisons. Finally,
      several secondary themes are discussed, including the importance of place, types
      of analysis, variable definition, causal relationships among variables, types of
      healing, locus of control, discourses about religion and health, and the religion
      and health connection.

PMID- 14719522
TI  - [British primary health care in the melting pot].

PMID- 14719523
TI  - Oncology nursing bibliography.

PMID- 14719524
TI  - Duplicate publication.

PMID- 14719525
TI  - Inhibition of the gravitropic bending response of flowering shoots by salicylic
      acid.
AB  - The upward gravitropic bending of cut snapdragon, lupinus and anemone flowering
      shoots was inhibited by salicylic acid (SA) applied at 0.5 mM and above. This
      effect was probably not due to acidification of the cytoplasm, since other weak
      acids did not inhibit bending of snapdragon shoots. In order to study its mode of
      inhibitory action, we have examined in cut snapdragon shoots the effect of SA on
      three processes of the gravity-signaling pathway, including: amyloplast
      sedimentation, formation of ethylene gradient across the stem, and differential
      growth response. The results show that 1 mM SA inhibited differential ethylene
      production rates across the horizontal stem and the gravity-induced growth,
      without significantly inhibiting vertical growth or amyloplast sedimentation
      following horizontal placement. However, 5 mM SA inhibited all three gravity
      induced processes, as well as the growth of vertical shoots, while increasing
      flower wilting. It may, therefore, be concluded that SA inhibits bending of
      various cut flowering shoots in a concentration-dependent manner. Thus, at a low
      concentration SA exerts its effect in snapdragon shoots by inhibiting processes
      operating downstream to stimulus sensing exerted by amyloplast sedimentation. At
      a higher concentration SA inhibits bending probably by exerting general negative
      effects on various cellular processes.

PMID- 14719526
TI  - Current awareness in NMR in biomedicine.

PMID- 14719527
TI  - Physical properties and sixth graders' acceptance of an extruded ready-to-eat
      sweetpotato breakfast cereal.
AB  - Extruded ready-to-eat breakfast cereals (RTEBCs) were made from varying levels of
      sweetpotato flour (SPF), whole-wheat bran (WWB), and extrusion cooking. Moisture,
      protein, and ash contents were lower in the 100% SPF than the 100% WWB.
      Carbohydrate, beta-carotene, and ascorbic acid contents were higher in the 100%
      SPF. Fat, thiamin, riboflavin contents, bulk densities, and the water absorption
      index were similar for the cereals. However, the expansion ratio was highest in
      the 100% SPF cereal. The 100% WWB had the lightest color and most fibrous
      morphology. Extruded RTEBC containing 100% SPF and 75%/25% SPF/WWB were well
      liked and acceptable to sixth graders attending an elementary school in Auburn,
      Alabama, but the 100% WWB was unacceptable.

PMID- 14719528
TI  - Psychiatry in pictures. William Kurelek (1927-1977), The Nightmare (detail),
      graphite on paper.

PMID- 14719529
TI  - [Abstracts of the 30th Congress of Czech Pathologists. Brno, May 23-25, 2003].

PMID- 14719530
TI  - [Electronic library].

PMID- 14719531
TI  - Proceedings of the European Consensus Conference on Medical Treatment of Non
      Small Cell Lung Cancer.

PMID- 14719532
TI  - WGW02. Proceedings of the International Workshop on Biologically Inspired
      Robotics, dedicated to William Grey Walter. August 2002, Bristol.

PMID- 14719533
TI  - Adaptive and failed CNS neuroplasticity: A tribute to Carl Cotman.

PMID- 14719534
TI  - Focus on psychiatry in Japan.

PMID- 14719535
TI  - Neuromuscular disorders:gene location.

PMID- 14719536
TI  - Mitochondrial encephalomyopathies:gene mutation.

PMID- 14719537
TI  - Congenital myasthenic syndromes:gene mutations.

PMID- 14719538
TI  - Measuring the degree of spatial correlation between histological features in thin
      sections of brain tissue.
AB  - Histological features visible in thin sections of brain tissue, such as neuronal
      perikarya, blood vessels, or pathological lesions may exhibit a degree of spatial
      association or correlation. In neurodegenerative disorders such as AD, Pick's
      disease, and CJD, information on whether different types of pathological lesion
      are spatially correlated may be useful in elucidating disease pathogenesis. In
      the present article the statistical methods available for studying spatial
      association in histological sections are reviewed. These include tests of
      interspecific association between two or more histological features using chi2
      contingency tables, measurement of 'complete' and 'absolute' association, and
      more complex methods that use grids of contiguous samples. In addition, the use
      of correlation matrices and stepwise multiple regression methods are described.
      The advantages and limitations of each method are reviewed and possible future
      developments discussed.

PMID- 14719539
TI  - Subcortical hematoma caused by cerebral amyloid angiopathy: does the first
      evidence of hemorrhage occur in the subarachnoid space?
AB  - Six autopsy cases of subcortical hematoma caused by CAA were examined to
      elucidate the primary site of hemorrhage. Immunohistochemistry for amyloid beta
      protein (A beta) revealed extensive CAA in the intrasulcal meningeal vessels
      rather than in the cerebral cortical vessels. All of the examined cases had
      multiple hematomas in the subarachnoid space, mainly in the cerebral sulci, as
      well as intracerebral hematomas. Each intracerebral hematoma was connected to the
      subarachnoid hematomas at the depth of cerebral sulci or through the lateral side
      of the cortex. There was no debris of the cerebral cortical tissue in the
      subarachnoid hematomas. In case 2, another solitary subarachnoid hematoma, which
      was not connected to any intracerebral hematoma, was seen. In all of these
      subarachnoid hematomas, many ruptured A beta-immunopositive arteries were
      observed. These ruptured arteries did not accompany any debris of the brain
      tissue, some of them were large in diameter (250-300 microm), and several of them
      were far from the cerebral cortex. Therefore, it was considered that they were
      not cortical arteries but meningeal arteries. Within the cerebral cortex, there
      were only a few ruptured arteries associated with small hemorrhages. There were
      no ruptured vessels within the intracerebral hematomas. There was a strong
      suggestion that all of the subarachnoid hematomas, including the solitary one in
      case 2, originated from the rupture of the meningeal arteries. The present study
      indicates that in some cases of subcortical hematoma caused by CAA, the primary
      hemorrhage occurs in the subarachnoid space, in particular the cerebral sulci,
      because of rupture of multiple meningeal arteries. Infarction occurs subsequently
      in the cortex around the hematoma, the hematoma penetrates into the brain
      parenchyma, and finally, a subcortical hematoma is formed.

PMID- 14719540
TI  - Morphological changes and stress responses in neurons in cerebral cortex
      infiltrated by diffuse astrocytoma.
AB  - Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause
      epilepsy and focal neurological deficits, but the cellular pathology of
      peritumoral cortex remains poorly defined. The aims of the present study were to
      define the morphological changes which occur in neurons in tumor-infiltrated
      cerebral cortex, and to determine whether peritumoral neurons show expression of
      cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28)
      were identified with areas of both tumor-infiltrated cortex and apparently non
      infiltrated cortex. Immunohistochemistry was performed to structural neuronal
      proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth
      associated protein-43 and to injury response proteins (poly(ADP-ribose)
      polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex
      revealed neuronal loss and architectural disarray compared to non-infiltrated
      cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their
      neuritic processes showed increasing tortuosity, varicosity, fragmentation and
      loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose)
      polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and
      non-infiltrated cortex, but c-jun expression was greater in areas of tumor
      infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma
      demonstrate, therefore, a sequence of morphological alterations in their
      dendritic, somatic and axonal compartments, and demonstrate a cell stress
      response. The patterns of cellular pathology identified suggest possible
      mechanisms, by which neurons are damaged and eventually lost in peritumoral
      brain.

PMID- 14719541
TI  - Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary
      tumors in craniospinal metastases: do they have a significant role?
AB  - Cytokeratin (CK)7 and CK20, the low molecular weight cytokeratins, have been
      found to have a benefit in the differential diagnosis of some epithelial
      neoplasms. In the present study, the actual role of these markers in the search
      of primary tumors in 32 patients with craniospinal metastasis of an unknown
      primary site at presentation, is evaluated. A series of 36 patients with a known
      primary tumor were presented for comparison. In the first group, two CK7 and CK20
      expression profiles were observed; 87% of metastatic tumors were CK7+/CK20- and
      13% CK7-/CK20-. The lung was the major source (82%) of CK7+/CK20- metastatic
      tumors, whereas it represented only 38% of primary tumor in the second group of a
      known primary site (P=0.006). Given the fact that metastatic tumors to the
      craniospinal axis of an unknown primary site are frequently CK7+/CK20-, and they
      have commonly metastasized from the lung, it is doubtful that
      immunohistochemistry is really helpful. However, CT scan and MRI of the chest
      still play an important role. Many patients in the present study had to undertake
      these imaging studies, regardless of the CK7/CK20 result. The immunostains may be
      useful in cases with other expression profiles, but such examples constituted
      only a minority in the present study.

PMID- 14719542
TI  - Expression of extracellular matrix markers in benign meningiomas.
AB  - Meningiomas have mesenchymal differentiation and studies have confirmed that
      meningiomas express intermediate filaments of both mesenchymal and epithelial
      types including vimentin and keratin. To further characterize their mesenchymal
      properties, particularly the role of factors requiring adhesion, extracellular
      matrix degradation, and migration, meningiomas were examined for a panel of
      extracellular matrix markers. Immunoreactivity to the matrix metalloproteinases,
      MMP-2 and MMP-9, and their tissue inhibitor, TIMP-1, and to an adhesion factor,
      galectin-3 were found in the majority of cases. The present study suggests that
      expression of these factors in benign meningiomas is ubiquitous and unrelated to
      tumor location. Therefore, these factors of the extracellular matrix may be
      potential targets of future therapy.

PMID- 14719543
TI  - Two distinct subgroups of senile dementia of Alzheimer type: quantitative study
      of neurofibrillary tangles.
AB  - The heterogeneity of senile dementia of Alzheimer type (SDAT) has been suggested
      by some authors clinically and neuropathologically. The heterogeneity of SDAT was
      investigated based on quantification of NFT combining Braak and Braak's
      neuropathological staging and the density of NFT in various areas of the cerebral
      cortex. Brain tissues were examined from 16 autopsy cases with clinically late
      onset dementia (> age 65) and neuropathologically diagnosed dementia of Alzheimer
      type (DAT). Gallyas-Braak staining was used for the quantification of NFT. The
      density of NFT was examined in the precentral gyrus, middle temporal gyrus (T2),
      parahippocampal gyrus and the amygdaloid nucleus. The 16 cases studied were
      divided into two groups depending on the number of NFT in the cortex (cut-off
      score: 5/mm2): the AD-like group (NFT > or = 5/mm2) and the common group (NFT <
      5/mm2). The density of NFT in the precentral gyrus (t(3.225) = -9.007, P = 0.002)
      and T2 (t(3.365) = -3.774, P = 0.027) in the AD-like group was significantly
      higher than those in the common group. However, no significant difference was
      observed in the parahippocampal gyrus between the two groups (t(14) = -0.318,
      NS). Moreover, there were no significant differences between the two groups as
      regards age at onset and the duration of the illness. The present study revealed
      the possible existence of two subgroups in SDAT having significantly different
      NFT densities in various areas of the cerebral cortex without any significant
      difference in their duration of illness. This classification has no relationship
      to Braak and Braak's staging, which depends only on the distribution of NFT,
      irrespective of their density. Arai et al. revealed that the NFT density in AD
      was significantly higher than in SDAT. We suggest that the neuropathological
      findings of the AD-like group in SDAT resemble those of presenile AD.

PMID- 14719544
TI  - Brain tissue microarrays in dementia research: white matter microvascular
      pathology in Alzheimer's disease.
AB  - Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from
      different donor paraffin blocks relocated into one recipient block, allowing for
      efficient histopathological studies by fluorescence in situ hybridization, RNA in
      situ hybridization or immunohistochemistry. On the background of the increasing
      interest of the TMA technique in cancer research and the suggestion of its
      application also in studies of non-neoplastic intracranial disorders, the
      technique was applied to pathologic white matter in AD brains. Eight cases with
      AD and concomitant white matter pathology were neuropathologically diagnosed on
      whole brain coronal slides. The TMA technique was used to grade severity of white
      matter pathology and to quantify small vessels with traditional staining and
      immunohistochemical markers. These measurements were compared with the whole
      brain neuropathological assessment. The technique produced good results with
      preserved tissue structures as confirmed by the whole brain evaluation. Severity
      of white matter pathology evaluated on the TMA cores correlated negatively with
      small vessel quantities, and statistically significant differences in vessel
      quantities paralleled different grades of white matter pathology. It is concluded
      that the TMA technique could be further utilized in studies of dementing
      disorders, and may have its advantages in large, clinically well-characterized
      materials (e.g. in quantitative mapping of white matter changes).

PMID- 14719545
TI  - Widespread vertebral and epidural venous plexus metastasis of prostatic carcinoma
      presenting wedge-shaped radial lesions in the spinal cord.
AB  - The present case is the first autopsy case of prostatic carcinoma presenting
      widespread spinal epidural venous plexus tumor cell emboli with wedge-shaped
      spinal cord lesions. There has been no previous report of prostatic carcinoma
      showing tumor cell emboli in the spinal and cranial base epidural venous plexus,
      in spite of the fact that the incidence of vertebral metastasis in prostatic
      carcinoma is high, and that presence of continuity from pelvic organs to venous
      plexus around vertebrae, up to foramen magnum, has been reported. The present
      case shows that the possibility of spinal cord injury, not by direct compression,
      but by venous circulatory disturbance as a result of tumor cell emboli to veins,
      should be taken into consideration on medical treatment of prostatic carcinoma.

PMID- 14719546
TI  - Extracerebral ectopic mass with huge cysts in the anterior cranial cavity.
AB  - In the present study, an unusual example of malformation in a 9-day-old-girl, in
      whom an extracerebral ectopic mass with cysts was found in the anterior cranial
      cavity, is reported. The brain proper was well developed. The mass was connected
      to the cerebral base and consisted of neuroglial tissue showing various
      characteristics of differentiation, including cerebellar cortex and monoaminergic
      neurons. The ectopia may have developed from the mediobasal portion of the
      embryonic telencephalon.

PMID- 14719547
TI  - Primary frontal-lobe germinoma appearing as a large cyst.
AB  - In the present case, a primary frontal-lobe germinoma in a 20-year-old man is
      reported. This is the first such case to be investigated by autopsy. The tumor
      appeared on a CT scan as a large cystic lesion in the frontal-lobe white matter.
      At autopsy, the typical two-cell histology pattern was seen mainly in the area of
      the cyst wall. Although cyst formation is a frequent feature of germinomas, the
      presence of a large cystic lesion in the cerebral white matter, as demonstrated
      in the present case, is very rare. The present case provides further radiographic
      data that might be useful for the future diagnosis of this tumor, which is
      radiosensitive and potentially curable.

PMID- 14719548
TI  - Senile dementia of the neurofibrillary tangle type (tangle-only dementia):
      neuropathological criteria and clinical guidelines for diagnosis.
AB  - Senile dementia of the NFT type (SD-NFT) is a subset of dementia in the elderly,
      characterized by numerous NFT in the hippocampal region and absence or scarcity
      of senile plaques throughout the brain. Senile dementia-NFT has also been
      referred to as tangle-only dementia, NFT-predominant form of SD, SD with tangles,
      or limbic NFT dementia. Herein are proposed the criteria for neuropathological
      diagnosis of SD-NFT: (i) late-onset dementia with abundant NFT in the hippocampal
      region and absence or scarcity of senile plaques (amyloid beta protein deposits)
      throughout the brain; and (ii) exclusion of other dementias with NFT. Some
      elderly individuals suffering from memory disorder without obvious dementia have
      neuropathological findings similar to SD-NFT, and they would represent a
      condition in the process of formation of the SD-NFT pathology. Guidelines for the
      clinical diagnosis of SD-NFT are also proposed; development of reliable
      diagnostic tests is necessary to differentiate AD and other neurodegenerative
      dementias from SD-NFT.

PMID- 14719549
TI  - Pick body disease and Pick syndrome.
AB  - Diagnostic criteria for Pick's disease have been criticized from many different
      viewpoints. This confusion is mainly derived from the ambiguity of this term
      'Pick's disease' (PD), which may imply either purely histological findings, such
      as Pick body (PB), or a characteristic clinical syndrome that could occur even in
      the absence of PB. This taxonomic confusion will be circumvented by introducing
      the diagnostic term 'Pick body disease' to designate patients with the
      characteristic argyrophilic inclusions purely on histological grounds. In
      parallel, employment of 'Pick syndrome' to describe the time-honored clinical
      features may be more convenient and less confusing than PD because PD implies
      either the presence of PB or the clinical features, two aspects not necessarily
      linked to each other. Three-dimensional reconstruction of PB confirmed that tau
      like immunoreactivity was accentuated at their periphery, as was recognized with
      the Bodian method. Preferential affinity of three-repeat tau pathology, as seen
      in Pick body disease, to the Bodian over the Gallyas method is distinct from the
      reversed affinity (the Gallyas over the Bodian method) of four-repeat tau
      pathology, as seen in corticobasal degeneration and in argyrophilic grains. This
      preference of silver staining is compatible with the mixed three- and four-repeat
      tau pathology, as seen in NFT of the Alzheimer's type, which are stained with
      both the Bodian and Gallyas staining. This will provide a practical basis on
      which to differentiate these disorders based on their distinctive tau species and
      possible relation of tau species to staining profile on these silver methods.

PMID- 14719550
TI  - Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome).
AB  - Two familial cerebro-vascular diseases characterized by different cerebral
      arterial pathologies and presenting in non-hypertensive young and middle-aged
      adults are described. Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is characterized by the deposition of
      smudged periodic acid-Schiff (PAS)-positive granules known as granular
      osmiophilic materials (GOM) in the media of small arteries and arterioles. The
      medial smooth muscle cells are completely lost, and intense adventitial fibrosis
      is present. Cerebral autosomal recessive arteriopathy with subcortical infarcts
      and leukoencephalopathy (CARASIL), or Maeda syndrome, is characterized by intense
      arteriolosclerosis without GOM deposition. Fibrous intimal proliferation, hyaline
      degeneration of the media, thickening and splitting of the internal elastic
      lamina, and concentric narrowing of the lumen are characteristic features. In PAS
      preparation, small arteries are occasionally stained homogeneously due to
      exudative changes, but never exhibit granular appearance in CARASIL (Maeda
      syndrome). Each of the small arterial changes is intense in the cerebral
      medullary and leptomeningeal arteries, leading to multifocal, confluent, or
      diffuse ischemic changes in the cerebrum. The authors suggest that CARASIL be
      referred to as 'Maeda syndrome' or 'CARASIL (Maeda syndrome)' to avoid confusion
      with CADASIL.

PMID- 14719551
TI  - Idiopathic hypertrophic pachymeningitis.
AB  - Idiopathic hypertrophic pachymeningitis is a rare disorder of unknown origin. It
      is a fibrosing inflammatory process that involves the dura mater. Herein are
      described 14 patients with idiopathic hypertrophic pachymeningitis; their
      clinical, laboratory and radiological findings, as well as their treatment, are
      analyzed. Neuropathological findings of six cases including two autopsied cases
      are also presented. The main clinical features were headache and cranial nerve
      palsies. Many patients had mild to moderate elevation of C-reactive protein, and
      three patients had perinuclear antineutrophil cytoplasmic antibody. The CSF in
      most cases showed inflammatory changes. Neuroimaging studies revealed diffuse or
      localized thickening of the dura, and MRI findings were key to diagnosis of this
      disorder. The clinical course was chronic. All patients were treated with
      corticosteroid and improved intially, but half of them experienced relapses. Two
      patients received surgical intervention. Pathological examination in two
      autopsied cases revealed diffuse thickening of the dura, especially in the
      posterior part of the falx cerebri and the tentorium cerebelli. Microscopic
      examination of the dura showed dense fibrosis with inflammatory cell infiltration
      composed mainly of lymphocytes. The cell infiltration was marked at the surface
      of the dura mater. One case had necrotizing vasculitis of the small arteries
      located in the dura and the cerebral surface. There were no giant cells,
      caseation necrosis, or epitheloid granuloma. Four patients underwent biopsy of
      the dura, and the pathological study showed non-specific inflammatory changes.
      The relationship of idiopathic hypertrophic pachymeningitis with connective
      tissue disease or vasculitis syndrome is discussed.

PMID- 14719552
TI  - Aceruloplasminemia, an iron metabolic disorder.
AB  - Aceruloplasminemia is an inherited disorder of iron metabolism caused by the
      complete lack of ceruloplasmin ferroxidase activity caused by mutations in the
      ceruloplasmin gene. It is characterized by iron accumulation in the brain as well
      as visceral organs. Clinically, the disease consists of the triad of adult-onset
      neurologic disease, retinal degeneration and diabetes mellitus. The neurological
      symptoms, which include involuntary movements, ataxia, and dementia, reflect the
      sites of iron deposition. Severe iron overload and extensive neuronal loss were
      observed in the basal ganglia, while iron deposition and neuronal cell loss were
      trivial in the frontal cortices. The cerebellar cortex showed marked loss of
      Purkinje cells. Iron deposition was more prominent in the astrocytes than in the
      neurons. Excess iron functions as a potent catalyst of biologic oxidation.
      Astrocytic deformity and globular structures are characteristic features in
      aceruloplasminemia brains. The globular structures in the astrocytes were seen in
      proportion to the degree of iron deposition and reacted positively to anti-4
      hydroxynonenal, one of the indicators of lipid peroxidation, and anti-ubiquitin
      antibodies, but not to anti-alpha-synuclein antibody. The lack of ceruloplasmin
      may primarily damage astrocytes in the aceruloplasminemia brains through lipid
      peroxidation. Ceruloplasmin may play an essential role in neuronal survival in
      the central nervous system.

PMID- 14719553
TI  - Neuronal intranuclear hyaline inclusion disease.
AB  - Neuronal intranuclear hyaline inclusion disease (NIHID) is a rare
      neurodegenerative disorder characterized pathologically by the presence of
      eosinophilic intranuclear inclusions in neuronal and glial cells. It has been
      considered to be a heterogeneous disease entity because the clinical pictures of
      previously described cases were highly variable. In the present review, reported
      NIHID cases have been categorized into three clinical subgroups according to
      onset and disease duration, and the clinical phenotype of each subgroup is
      discussed. Neuronal intranuclear inclusions (NII) in NIHID are ubiquitinated and
      their prevalence is inversely correlated with neuronal loss, suggesting that NII
      formation is a protective mechanism involving the ubiquitin-proteasome-dependent
      proteolytic pathway. In several polyglutamine diseases, disease-related proteins
      containing abnormally expanded polyglutamine tracts aggregate in neuronal nuclei,
      resulting in NII formation. The similarity between NII in NIHID and polyglutamine
      diseases suggests that they are formed during a common proteolysis-related
      process that takes place in the nucleus. Although the pathogenetic mechanism
      underlying NIHID remains unknown, the data reviewed here suggest that it might be
      related to accumulation of as yet unidentified abnormal proteins or dysfunction
      of the intranuclear ubiquitin-proteasome pathway.

PMID- 14719554
TI  - Subacute speech apraxia and consciousness disturbance in a 57-year-old non
      alcoholic man.

PMID- 14719555
TI  - A 25-year-old woman with multiple brain tumors who died after a course of 1 year
      and 6 months.

PMID- 14719556
TI  - Exogenous lipoid pneumonia: serial chest plain roentgenography and high
      resolution computerized tomography findings.
AB  - Between May 1988 and July 2002, six patients with pneumonia due to diesel,
      animal, or vegetable oil aspiration were admitted to Kaohsiung Medical University
      Hospital. The purpose of this study was to demonstrate distinctive radiographic
      findings of oil-induced lipoid pneumonitis on initial serial chest roentgenograms
      and high-resolution computerized tomography (CT) scans. Initial chest
      roentgenograms (n = 6), CT scans (n = 6), and roentgenography and CT follow-up
      studies were analyzed retrospectively by two chest radiologists and two surgeons,
      focusing on the pattern and distribution of parenchymal abnormalities. The most
      common location was the right middle lobe, followed by the right lower lobe, the
      left lower lobe, and the lingular lobe. Follow-up chest roentgenograms (n = 6)
      showed complete disappearance of the parenchymal lesions in only one patient and
      partial decrease in the extent of lesions in five patients. Lipoid pneumonia
      presents non-specific findings on chest roentgenography. It is commonly located
      in both lower and the right middle lobes. On high-resolution CT, the lesions
      appear most commonly as areas of consolidation, ground-glass attenuation mixed
      with paving pattern, and poorly defined nodules.

PMID- 14719557
TI  - Carbon dioxide angiography in lower limbs: a prospective comparative study with
      selective iodinated contrast angiography.
AB  - This was a prospective comparison of the accuracy and image quality of carbon
      dioxide digital subtraction angiography (CO2 DSA) and iodinated contrast digital
      subtraction angiography (ICDSA) in evaluating lower extremity arteries and
      patient tolerance of the procedures. Selective DSA was performed in 14 Taiwanese
      patients who were diagnosed with peripheral artery occlusive disease (PAOD). Both
      contrast materials were administered through mechanical injectors. Post
      processing of the image used pixel shifting. Images of vessels were divided into
      22 anatomic segments and evaluated by two experienced radiologists. A four-point
      scale was used to classify diseased vessels. Two interpreters rated the CO2 DSA
      image against the ICDSA image on a three-point scale. Patient tolerance was
      assessed from verbal descriptions. Cohen's kappa was used to determine
      interobserver agreement and descriptive statistics were used to summarize patient
      experience. Interobserver agreement ranged from fair to excellent, with most
      being good or excellent. Three patients (21.4%) could not tolerate the whole
      procedure and nine patients (64.3%) reported discomfort during the CO2 DSA
      procedure. CO2 DSA image quality was better for the thigh than the distal runoff
      and pelvic regions. Our results showed that selective CO2 DSA cannot replace
      ICDSA as a routine diagnostic tool for PAOD because it does not give images of
      comparative quality.

PMID- 14719558
TI  - Intravitreous recombinant tissue plasminogen activator and gas to treat
      submacular hemorrhage in age-related macular degeneration.
AB  - We evaluated the safety and efficacy of intravitreous recombinant tissue
      plasminogen activator (rTPA) and gas for the treatment of submacular hemorrhage
      in age-related macular degeneration (ARMD). From January 2000 to April 2002, we
      enrolled 15 patients with submacular hemorrhage secondary to ARMD. All patients
      received 100 microg rTPA and 0.3 mL perfluoropropane intravitreously.
      Postoperatively, all patients were kept in a supine position for 4 hours followed
      by a face-down position for 4 days. Anatomic and functional results were
      evaluated during a follow-up period of 6 to 19 months. Submacular blood was
      completely displaced in 12 patients (80%) and partially in three (20%). Best
      postoperative visual acuity improved in all 15 eyes; in seven eyes (47%), the
      improvement was two or more lines. Final visual acuity improved in 12 eyes,
      remained stable in two eyes, and worsened in one eye. Onset of hemorrhage within
      21 days was associated with better gains of lines in best postoperative (p =
      0.0256) and final visual acuity (p = 0.044). Although two patients developed mild
      breakthrough vitreous hemorrhage within 1 day after treatment, no rTPA-related
      retinal toxicity was observed. Intravitreous injections of rTPA and gas are safe
      and effective in improving visual acuity in patients with submacular hemorrhage
      secondary to ARMD. Although the final visual outcome is often limited by the
      progression of the disease, significant and stable visual recovery over an
      extended follow-up period is possible using this easy and convenient technique.

PMID- 14719559
TI  - Relationship between carpal tunnel syndrome and wrist angle in computer workers.
AB  - Carpal tunnel syndrome (CTS) is the most widely known entrapment neuropathy. The
      aim of this study was to assess the incidence of CTS in a group of computer
      workers by typical symptoms, median nerve conduction studies, and their
      combinations. The posture of extended wrists while typing on a computer keyboard
      seems to be a predisposing factor for CTS. However, the correlation between wrist
      extension angle and the incidence of CTS is not well known. Forty-five subjects
      (mean age, 38.8 +/- 7.8 years) who used a computer for more than 6 hours daily in
      a medical center in southern Taiwan were studied. All completed questionnaires to
      ascertain their age, employment duration, dominant hand, and the severity of
      symptoms. Physical examinations (Tinel's sign and Phalen's test) were performed
      by a physician. The maximal wrist extension angle when typing on a computer
      keyboard was also measured by the same physician. Nerve conduction studies were
      performed on each subject to determine the severity of CTS. Results showed that
      the incidence of CTS in the computer workers was 16.7% (15 of 90 hands). Twelve
      subjects showed electrodiagnostic evidence of CTS: it involved the dominant hand
      in seven, the non-dominant hand in two, and bilateral hands in three. The
      severity of clinical symptoms was compatible with the findings of the nerve
      conduction studies. Among the major predisposing factors, we found significant
      correlation between CTS development and the wrist extension angle while typing on
      a computer keyboard. Computer workers who kept their wrists extended by more than
      20 degrees were at greater risk of developing CTS.

PMID- 14719560
TI  - Exercise-induced acute spinal subdural hematoma: a case report.
AB  - A 63-year-old woman developed acute back pain and sciatica after playing hula
      hoop. Urinary incontinence was also noted. Magnetic resonance imaging revealed
      acute thoracolumbar spinal subdural hematoma. After emergency surgical
      decompression and evacuation of the spinal subdural hematoma, the patient had
      good recovery without any postoperative neurologic deficit. In this article, we
      describe and review the clinical presentations, characteristic findings from
      imaging studies, and treatment of spinal subdural hematoma.

PMID- 14719561
TI  - Rotationplasty for limb salvage in the treatment of malignant tumors: a report of
      two cases.
AB  - Limb salvage is now more common than amputation after radical excision to treat
      malignant tumors. In a skeletally immature patient who has malignant tumors in a
      lower extremity, rotationplasty offers a more reliable and durable option than
      other limb salvage procedures. It is an excellent method of resolving the problem
      of unequal leg lengths, and preserves best limb function with few complications.
      Here, we present our experience with rotationplasty for limb salvage in the
      treatment of malignant tumors, with good functional results seen in follow-up
      examination 11 years after surgery.

PMID- 14719562
TI  - Perforated duodenum--an unusual etiology of Fournier's disease: a case report.
AB  - Fournier's disease, a form of necrotizing fasciitis, is a rapidly progressing
      subcutaneous infection of the male genitalia. We report a case of Fournier's
      disease with the unusual etiology of a perforated duodenum. This patient suffered
      from progressive right scrotal swelling after percutaneous transhepatic
      cholangeal drainage. Scrotal exploration revealed a large abscess with muscle
      necrosis that had spread up to the right retroperitoneal space. Radiologic
      studies and second abdominal exploration documented the origin as a perforated
      duodenum. The pus distribution in this case suggested that the infection process
      differed from that in previous reports. In future cases of Fournier's disease
      involving previous abdominal events, we recommend that abdominal origins be
      carefully surveyed before scrotal exploration.

PMID- 14719563
TI  - Sinonasal NK/T-cell lymphoma with upper gastrointestinal bleeding: a case report.
AB  - Natural killer (NK)/T-cell lymphoma is the most common malignant lymphoma among
      sinonasal lymphomas. Diagnosis is difficult and prognosis is poor. Herein, we
      report the case of a 22-year-old male patient with sinonasal NK/T-cell lymphoma
      who first presented with nasal obstruction and left facial swelling. There was a
      mushroom-like mass over the hard palate, diffuse mucosal swelling in the left
      nasal cavity, and left orbital cellulitis. The patient underwent a Caldwell-Luc
      operation, functional endoscopic sinus surgery, and wide excision of the palate
      tumor. Pathologic examination of the maxillary sinus, nasal cavity, and palate
      tumor showed an NK/T-cell lymphoma. Two days after the operation, the patient
      suddenly had bloody stool and suffered hematemesis. A series of examinations
      revealed a small intestinal hemorrhage. Emergent exploratory laparotomy showed an
      ulcerative tumor mass with bleeding over the jejunum. Pathologic examination of
      the mass showed that it was the same as the sinonasal mass, an NK/T-cell
      lymphoma. We reviewed previous studies on nasal NK/T-cell lymphoma and found no
      report discussing patients with NK/T-cell lymphoma of both nasal and non-nasal
      origins. From this case, we learned that in patients with sinonasal NK/T-cell
      lymphoma, other sites may be involved.

PMID- 14719564
TI  - Cardiac computed tomography imaging: a history and some future possibilities.
AB  - Cardiac computed tomography (CT) is a special subset of CT, a subject about which
      much has been written in terms of the underlying concepts and mathematics and the
      sociologic impact. Cardiac CT has passed through three, chronologically
      overlapping, developmental stages and is now in its fourth stage of development.
      The first stage was fluoroscopy-based CT (1972-1995) stimulated by physiologic
      research needs, and the next was clinical CT-based exploration (1975-1980) of the
      potential of clinical CT in cardiology. This was followed by the electron beam CT
      based stage (1980-present), which was the first CT approach applicable to
      clinical cardiology. Finally, volume-scanning CT imaging methods achieved with
      multislice scanning approaches of helical CT and by flat panel-based CT (1990
      present), show great promise for clinically applicable CT of the cardiovascular
      system.

PMID- 14719565
TI  - Physics and dosimetry in computed tomography.
AB  - CT data acquisition and image reconstruction techniques are closely related to
      image quality and patient radiation dose. There is little question that
      technological developments currently underway will change the nature of both, and
      result in improved quality and diagnostic value of cardiovascular CT images while
      hopefully minimizing radiation dose to the patient.

PMID- 14719566
TI  - Coronary artery calcium and its relationship to coronary artery disease.
AB  - Electron-beam computed tomography (EBCT) and the recent generation of multi-slice
      computed tomography scanners (MSCT) permit high-resolution imaging of the beating
      heart and the coronary arteries. The visualization of coronary calcium offers the
      opportunity to non-invasively obtain direct information on coronary anatomy and
      plaque burden. For clinical purposes, coronary calcium represents the presence of
      arteriosclerotic plaques. Coronary calcium is deposited in an actively regulated
      process related to lipid content of and apoptosis within coronary plaques. The
      amount of coronary calcium is related to the extent of coronary plaque disease,
      which has substantial diagnostic and prognostic implications. Visualization of
      coronary calcium by cardiac CT allows to non-invasively detect and localize
      coronary plaques and describe their distribution in the coronary tree.
      Approximately 50% to 70% of all plaques are calcified. Calcium cannot be used to
      reliably identify plaques at risk for developing complications such as rupture or
      erosion with ensuing thrombus formation. However, data are accumulating that
      indicate that calcium is an indicator of coronary arteriosclerotic disease
      activity. A scan negative for coronary calcium has a high negative predictive
      value indicating absence of stenotic coronary artery disease and an excellent
      short- to mid-term prognosis. Studies using serial CT scans indicate that the
      annual progression of coronary calcium varies between 30% to 50% in symptomatic
      or high-risk individuals and 0% to 20% in patients treated effectively with lipid
      lowering medication. An increased rate of progression of coronary calcium seems
      to indicate a substantially increased risk for adverse cardiac events.

PMID- 14719567
TI  - Clinical use of coronary calcium scanning with computed tomography.
AB  - EBT has undergone rigorous testing for reliability and validity of CAC
      measurements, and has been proven to be useful in identifying individuals with,
      or at risk for, coronary heart disease. Although MDCT is a promising tool for
      coronary calcium scoring, more studies are needed that compare EBT and MDCT scans
      in the same patients, especially with calcium scores of less than 100. Further
      radiation dose reduction strategies for MDCT are currently being evaluated. MDCT
      studies of progression, reproducibility, and outcomes are needed to fully
      evaluate its potential to measure and serially follow atherosclerosis compared to
      EBT. Studies examining the benefit of serial coronary calcium scoring to non
      invasively assess the progression or regression of coronary calcium are currently
      underway. EBT is a method that can be used to estimate the overall coronary
      atherosclerotic plaque burden. It can be used to diagnose the presence and
      determine the extent of coronary atherosclerosis; furthermore, the calcium score
      information can be used to assess the likelihood of advanced obstructive disease
      and to provide prognostic information. Finally, serial CAC measurements by EBT
      have the potential to determine the efficacy of therapeutic interventions by
      demonstrating progression, stabilization, or regression of coronary
      atherosclerotic disease during therapy.

PMID- 14719568
TI  - Clinical results of minimally invasive coronary angiography using computed
      tomography.
AB  - Fast, high-resolution CT techniques, such as EBCT and MDCT permit imaging of the
      coronary arteries. Continuous improvements in the capabilities of both
      technologies for visualization of the coronary lumen and detection of coronary
      artery stenoses are being made. Image quality currently is not robust enough in
      all patients to consider non-invasive coronary angiography by EBCT and MDCT a
      routine clinical tool. In selected patients and carefully performed, however,
      they show promise as means to exclude the presence of coronary artery stenoses in
      a non-invasive fashion. This may become a beneficial and important application of
      these technologies. Other possible applications pertain to smaller patient
      subsets, such as patients with anomalous coronary arteries, fistulas or
      aneurysms. The development of techniques to visualize non-calcified plaque is
      interesting with respect to assessment of coronary risk, but this requires
      further investigation.

PMID- 14719569
TI  - Computed tomography for assessment of cardiac chambers, valves, myocardium and
      pericardium.
AB  - The focus to date of MDCT has been primarily on CT applications for evaluating
      the coronary arteries, notably the measurement of coronary artery calcification,
      plaque characterization, and atherosclerotic lumen stenosis. This is because of
      the limited temporal resolution of CT, and the recent rapid improvements in MRI
      for cardiac applications. However, if the temporal resolution of MDCT can be
      improved, there will be a compelling argument for undertaking further CT
      validation studies. Feasibility of CT has already been established by EBT for
      general cardiac diagnosis. Modifications for MDCT include improved software
      methods for post processing ECG-gated scan data or higher speed CT hardware for
      faster image acquisition, both of which are being developed at this time. EBT is
      also evolving and continuously being refined so that the new generation of
      scanners have exposure times of 50 msec or less. There are many considerations in
      comparing the pros and cons of competing cardiac imaging modalities. Published
      diagnostic validations studies, convenience, procedure time, the comfort level
      (of patients and physicians), availability, and cost are all critical. The level
      of acceptance and the accuracy with which specific patient management questions
      can be appropriately answered are crucial issues in determining which diagnostic
      procedure to perform. However, the jury is still out regarding the ultimate role
      of CT in the diagnosis of heart disease; certainly the great potential of cardiac
      CT has not yet been fully realized.

PMID- 14719570
TI  - Imaging of myocardial microvasculature using fast computed tomography and three
      dimensional microscopic computed tomography.
AB  - In the past, much attention in imaging research was focused on the macroscopic
      morphology and patency of arteries. Only recently, research and clinical interest
      have shifted to the microcirculation and its impact on the long-term prognosis in
      patients with vascular diseases. This focus and newly developed therapeutic
      strategies require high-resolution imaging modalities, which do not focus
      exclusively on the macroscopic aspects of the arterial tree. Provided here is a
      comprehensive perspective of using computed tomography technology to image and
      quantify the function and morphology of myocardial and vascular adventitial
      microvessels in normal and disease states.

PMID- 14719571
TI  - Multidetector row computed tomography of the aorta and peripheral arteries.
AB  - MDCT represents a significant advance on SDCT and the advantages it brings are
      particularly clear in CTA applications. It allows cost effective assessment of
      longer segments of vascular territories to be imaged with higher spatial,
      contrast, and temporal resolution. It has replaced SDCT as the new CT standard
      and its technical abilities are rapidly approaching the temporal resolution of
      EBCT. With 3-D post processing tools its main benefit is in imaging studies
      customized to the patient's pathology, with greater measurement accuracy and
      reliable longitudinal assessment. MDCTA is increasingly applied not to individual
      vascular territories but to a complete assessment dictated by the pathology, such
      as the entire aorta and branch vessels in aneurysm evaluation and the aorta and
      the coronary arteries in dissection cases or the vascular and non-vascular chest
      in acute chest pain. Greater accuracy of vessel assessment will lead to a
      refinement of interventional and surgical techniques for an individual patient
      and facilitates conservative management of conditions that can be reliably
      monitored non-invasively and the development of intervention criteria. MDCTA will
      continue to increase its major role in peripheral vascular evaluation in the
      future though its reliability in assessing small vessels below the knee and in
      the foot remains to be conclusively proven to obviate the need for diagnostic
      catheter angiography.

PMID- 14719572
TI  - Venous thromboembolic disease: where does multidetector computed tomography fit?
AB  - Introduction of helical CT started a new era in the diagnosis of PE. It is
      noninvasive and readily available. Developments in helical CT technology
      (particularly introduction of multidetector scanners) improved image quality by
      decreasing the scanning time and slice thickness. With the addition of indirect
      CT venography to CT pulmonary angiography, CT also took the role of venous
      ultrasound, thus creating a single examination for diagnosis of VTD. On the other
      hand, CT is not perfect at all circumstances, especially in the evaluation of
      subsegmental arteries. Careful selection of patients for imaging studies will
      save time, cost, and radiation.

PMID- 14719573
TI  - Complementary results of computed tomography and magnetic resonance imaging of
      the heart and coronary arteries: a review and future outlook.
AB  - MR and CT imaging are emerging as promising complementary imaging modalities in
      the primary diagnosis of CAD and for the detection of subclinical atherosclerotic
      disease. For the detection or exclusion of significant CAD, both cardiac CT
      (including coronary calcium screening and non-invasive coronary angiography), and
      cardiac MRI (using stress function and stress perfusion imaging) are becoming
      widely available for routine clinical evaluation. Their high negative predictive
      value, especially when combining two or more of these modalities, allows the
      exclusion of significant CAD with high certainty, provided that patients are
      selected appropriately. The primary goal of current investigations using this
      combined imaging approach is to reduce the number of unnecessary diagnostic
      coronary catheterizations, and not to replace cardiac catheterization altogether.
      For the diagnosis of obstructive coronary atherosclerosis and for screening for
      subclinical disease, CT and MRI have shown potential to directly image the
      atherosclerotic lesion, measure atherosclerotic burden, and characterize the
      plaque components. The information obtained may be used to assess progression and
      regression of atherosclerosis and may open new areas for diagnosis, prevention,
      and treatment of coronary atherosclerosis. Further clinical investigation is
      needed to define the technical requirements for optimal imaging, develop accurate
      quantitative image analysis techniques, outline criteria for image
      interpretation, and define the clinical indications for both MR or CT imaging.
      Additional studies are also needed to address the cost effectiveness of such a
      combined approach versus other currently available imaging modalities.

PMID- 14719574
TI  - Bone density: its influence on implant stability after uncovering.
AB  - Primary implant stability and bone density are variables that have long been
      considered to be essential to achieving predictable osseointegration and long
      term clinical survival. Although the dentist can control most factors associated
      with implant survival, bone density is the one factor that cannot be controlled.
      Measuring implant stability would assist in determining if an implant has
      integrated and is ready for the fabrication of the final prosthesis. Changes in
      implant stability in each type of Bone Quality (BQ-1, -2, -3, and -4), which may
      occur with time, have not been studied. Such information could help identify well
      integrated implants and identify changes associated with impending implant
      failure. Several studies have used the Periotest instrument to study implant
      stability. Use of the Periotest implant stability will be studied during each
      phase of implant treatment for each bone density, and a range for clinically
      satisfactory integration will be suggested. Implant stability changes over time,
      and the changes are different for each bone density as the bone surrounding the
      nonhydroxyapatite implant becomes denser. This is clearly demonstrated in a
      postmortem histological specimen. The changes in implant stability (Periotest
      Values [PTVs]) are more apparent in BQ-1 and BQ-2 bone and less apparent in BQ-3
      and BQ-4 bone. The Periotest is capable of providing valuable information
      concerning favorable or unfavorable changes in the bone-implant interface after
      uncovering. In addition, it can help identify when an implant is ready to be
      loaded. A new range of PTVs (-5 to -2) is suggested for monitoring the status of
      implants. Implants with PTVs more positive than -2 would indicate a bone-implant
      complex that may be marginal.

PMID- 14719575
TI  - Characterization and dissolution behavior of sputtered calcium phosphate coatings
      after different postdeposition heat treatment temperatures.
AB  - There is a lack of correlation between specific properties of hydroxyapatite
      coating surfaces, osseointegration processes, and implant success. The aim of
      this study was to evaluate the relationship between well-characterized structural
      and chemical properties of radio-frequency sputtered calcium phosphate (CaP)
      coatings and their dissolution behavior. Sputtered CaP coatings were evaluated as
      sputtered (non-heat treated) or after 1 hour of postsputter heat treatments at
      400 degrees C or 600 degrees C. All coatings were characterized by X-ray
      diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared
      spectroscopy, and contact angle measurement. The dissolution behavior of CaP
      coatings in the presence and absence of proteins was also investigated. It was
      observed from this study that as-sputtered CaP coatings were amorphous. The 400
      degrees C heat-treated CaP coatings exhibited low crystallinity (1.9% +/- 0.4%),
      whereas the 600 degrees C heat-treated CaP coatings were highly crystalline
      (67.0% +/- 2.4%). The increase of Ca/P ratio, PO4/HPO4 ratio, and the number of
      PO4 peaks were observed to be consistent with the increase in heating temperature
      and the degrees of coating crystallinity. Phosphorus ions released from CaP
      coatings decreased with the increase of crystallinity of CaP coatings. In
      addition, immersion of CaP coatings in media containing proteins resulted in an
      increase in P ions released as compared with coatings immersed in media without
      proteins. It was concluded that the degree of CaP coating crystallinity can be
      controlled by varying the postdeposition heat-treatment temperature. It was also
      concluded that, aside from coating crystallinity, dissolution and reprecipitation
      of the coatings can be controlled by knowing the presence of proteins in the
      media and PO4/HPO4 ratio within the coatings.

PMID- 14719576
TI  - Selecting treatment options and sequencing treatment in the replacement of 2
      maxillary central incisors with implants: a case report.
AB  - This article describes treatment provided to replace 2 maxillary central incisors
      with implant-supported restorations. The site of a missing maxillary central
      incisor was treated utilizing a bone expansion technique to augment the labial
      hard and soft-tissue profiles at the time of implant placement. The adjacent
      central incisor tooth, although destined to be extracted, was retained to serve
      as an abutment for a fixed provisional restoration until the first implant was
      deemed to have successfully integrated. At the appointment to uncover this
      implant, the fractured tooth was extracted and an implant was immediately placed
      into the socket. The first implant was then used to support the provisional
      restoration during the healing phase of the second implant. The techniques
      utilized resulted in optimum soft-tissue contours, allowed the patient to have a
      comfortable and esthetic provisional restoration, and minimized the number of
      surgical procedures.

PMID- 14719577
TI  - The mandibular labial bar major connector.
AB  - The lower labial bar is rarely indicated as a major connector for a removable
      partial denture. It can be used satisfactorily when large mandibular tori
      interfere with conventional lingual bar placement or when the lower teeth are
      severely lingually tipped and placement of a lingual bar is not possible.

PMID- 14719578
TI  - Esthetics and super glue: a case report.
AB  - This article describes how a man attempted to repair damage to his maxillary
      teeth with super glue. Such action is discouraged, however, because of possible
      adverse reactions in the hard and soft tissues.

PMID- 14719579
TI  - Use of magnetic abutments for short endosseous implants following a fibula bone
      graft in an oral cancer patient: a case report.
AB  - Dental implant treatment is an indispensable portion of oral rehabilitation in
      patients who are to undergo reconstructive surgery following the removal of an
      oral cancerous lesion. However, ideal dental implant treatment cannot be achieved
      easily in patients who have undergone mandibular reconstruction with a free
      vascularized flap, usually because of the limited length, height, and width of
      the bone graft. Shorter implants (< 10 mm in length) therefore are occasionally
      used in vascularized fibula graft sites. In such cases, however, shorter implants
      tend to be overloaded, thereby endangering its longevity. In this article, we
      discuss how a magnetic abutment system was introduced for such a patient. This
      was designed to discourage overloading of the mandatory short implants. The
      outcome was successful without overloading 1.5 years after the placing of the
      mandibular overdenture.

PMID- 14719580
TI  - Coronary heart disease risk factors: known and the less known.

PMID- 14719581
TI  - Ferritin, a potent threat for acute myocardial infarction?
AB  - BACKGROUND: Studies conducted have yielded contradicting results on the role of
      ferritin as a risk factor for acute myocardial infarction (AMI). The relation of
      ferritin status to risk of AMI in Indian men, along with other established major
      risk factors like serum total cholesterol, HDL cholesterol, LDL cholesterol, VLDL
      cholesterol and triglycerides has not been documented previously. The hypothesis
      that increased serum ferritin was related to increased chances of AMI along with
      the risk factors was tested. METHODS: Case control study involving 145 men (100
      cases and 45 healthy control subjects) in the age group of 30-70 years. Serum
      ferritin levels were estimated by using ELISA, and other risk factors by
      enzymatic methods. RESULTS: Increased serum ferritin levels significantly (p <
      0.001) correlated with an increase of other risk factors in Indian male patients
      with AMI. CONCLUSION: Significant direct correlation between serum ferritin
      levels and risk of AMI was observed.

PMID- 14719582
TI  - Evaluation of cardiovascular status in severe leptospirosis.
AB  - OBJECTIVES: To note incidence and profile of cardiac involvement in severe
      leptospirosis in South Gujarat. METHODS: A study was carried out on twenty-five
      serologically proved leptospirosis patients referred to Government Medical
      College, New Civil Hospital, Surat between June 2002 to September 2002. In all
      the patients detailed history, physical examination and specific investigations
      were done to find out the incidence and profile of cardiac involvement in severe
      leptospirosis. RESULTS: Out of twenty-five seropositive patients, 14(56%) had
      cardiovascular manifestations. Electrocardiography abnormalities were seen in
      13(52%) patients. The commonest finding was first-degree AV block seen in II(44%)
      patients followed by ST-segment depression in four (16%) patients, T-wave
      inversion in leads II, III and avF in two (8%) patients, corrected QT-interval
      prolongation in three (12%) patients and ventricular premature beats in two (8%)
      patients. Atrial fibrillation was seen in only one patient. Left ventricular
      function as assessed by two-dimensional echocardiography was normal in all
      patients. CONCLUSION: In cardiovascular involvement of leptospirosis, although
      electrocardiographic abnormalities were commonly seen, there was no left
      ventricular dysfunction.

PMID- 14719583
TI  - Poisoning: an unnatural cause of morbidity and mortality in rural India.
AB  - BACKGROUND: Ninety-nine percent of fatal poisonings occur in developing
      countries, particularly among agricultural workers. In a particular area, it is
      important to known the magnitude and pattern of acute poisonings, as it is
      important for early diagnosis and treatment and also for preventive measures.
      METHODS: Hospital records of all unnatural causes of deaths were reviewed at Shri
      Vasantrao Naik Government Medical College, Yavatmal, Maharashtra during the five
      years period, 1997-2001. Autopsy records in fatal poisonings were studied for
      age, sex, residence, marital status, type of poison and manner of poisoning
      (accidental, suicidal or homicidal). Admission and death rates of acute
      poisonings were compared with those from other unnatural causes. RESULTS: Acute
      poisoning is the leading most cause of unnatural deaths and third common cause of
      emergency hospitalizations in this rural part of India. Of all fatal cases, 67%
      were males, 63% married, 83% with rural residence and 63.4% suicides. Responsible
      poison could not be ascertained in 16% of clinical and 9.9% of fatal cases.
      Insecticides were responsible for 35% of clinical and 55.4% of fatal cases.
      CONCLUSIONS: Young married males of rural background with agricultural occupation
      and failure of monsoon are the risk factors associated with poisoning cases.

PMID- 14719584
TI  - Hodgkin's lymphoma presenting as extradural spinal cord compression.
AB  - OBJECTIVES: Hodgkin's lymphoma presenting with spinal cord compression is rare.
      Reports estimate that only 5% of patients with Hodgkin's lymphoma have spinal
      cord compression. The objectives of this study were:- (1) To review the histology
      of all cases of Hodgkin's lymphoma causing spinal cord compression. (2) To
      correlate the findings with the clinical details- lymphadenopathy,
      hepatosplenomegaly, and marrow involvement. METHOD: This was a retrospective
      study, the period of study being between 1987-2002. All cases were taken from the
      histopathology record files, pathology department, NIMS, Hyderabad. The clinical
      profile of each case was noted and the histology reviewed. When necessary,
      immunohistochemistry with the necessary markers was performed. RESULT: There were
      12 cases, of which 11 were males, and one was a female. The patients ranged from
      8-62 years of age, with a median age of 32 years. The cord involvement was at
      different levels- thoracic(8), lumbar(2) and cervical(2). CONCLUSIONS: The
      histologic diagnosis of Hodgkin's lymphoma presenting as cord compression
      requires awareness of the condition. The close differential diagnoses include non
      specific inflammation, non-Hodgkin's lymphoma, tuberculosis and eosinophilic
      granuloma. Detailed clinical evaluation is essential for interpreting the
      histology.

PMID- 14719585
TI  - Pattern of lung cancer in elderly.
AB  - OBJECTIVES: The aim of the study was to evaluate the clinical spectrum of the
      lung cancer in the Indian patients. METHODS: All the patients above the age 60
      years referred to the chest clinic of Apollo Hospitals, during the period 1989
      2000 were evaluated for lung cancer with fibreoptic bronchoscopy, fluoroscopic
      guided transbronchial lung biopsy, transbronchial, needle aspiration and/or CT
      guided percutaneous fine needle aspiration biopsy. Retrospective data of 1400
      patients was analyzed statistically. RESULTS: There were 512 patients (439 males,
      73 females) with confirmed primary lung cancer. There were 62% ex-smokers, 10%
      current smokers and 28% non-smokers amongst males, whereas amongst females there
      were 10% ex-smokers and 90% non-smokers. Cough of more than 3 weeks duration was
      the commonest symptom seen in 85% (n = 435) followed by fever and weight loss.
      Radiologically the commonest feature was collapse-consolidation in 77% (n = 397).
      Central endobronchial tumours were seen in 204 patients (39.8%), whereas
      peripheral tumours were seen in 308 (60.2%). The diagnostic yield of
      transbronchial lung biopsy alone was as high as 48%, whereas the yield on CT
      guided percutaneous fine needle aspiration biopsy alone ranged from 32%-40%.
      There was no statistical difference in histological subtypes (non-small cell or
      small cell lung cancer) in the various groups studied. However, in those patients
      above the age of 80 years (group C) small cell lung cancer was more frequently
      seen. CONCLUSION: Primary lung cancer should always be suspected in elderly
      Indian subjects with unexplained cough and other constitutional symptoms of
      weight loss and fever.

PMID- 14719586
TI  - HLA genotyping in type-I autoimmune hepatitis in Western India.
AB  - OBJECTIVES: To analyze association of different HLA genotypes for predisposition
      to type-I autoimmune hepatitis in Western India. METHODS: This study was
      undertaken on patients of type-I autoimmune hepatitis (defined by international
      criteria by IAHG, 1999). HLA genotyping for class I and II was done in 20
      patients of autoimmune hepatitis and 100 healthy controls. Statistics were done
      using Halden's modification of Woolfs formula. RESULT: Significant association of
      autoimmune hepatitis was found amongst class I antigens--HLA B27 [20 vs. 0 %] &
      HLA cw4 [40 vs. 15 %] and amongst class II antigens--DRBI*01XX [25 vs. 2%],
      DRB1*14XX [30 vs. 12%], DRB1*15XX [40 vs. 25%] and DRB1*07XX [20 vs. 9 %] at DRB1
      locus. Stronger association was found with HLA B27, cw4 & HLA DRB1 *01XX.
      CONCLUSION: Our data indicate that predisposition to autoimmune hepatitis is
      different in Indian patients and not associated with HLA DRB1*03XX or *04XX, as
      seen in Western world.

PMID- 14719587
TI  - Drug-induced kidney diseases.
AB  - Drug-induced kidney disease constitutes an important cause of acute renal failure
      and chronic kidney disease in present day clinical practice. Different classes of
      drugs, by virtue of immunological mechanisms or direct toxicity initiate certain
      stereotyped renal responses. For most patients suffering from drug-induced
      nephropathy common risk factors which precipitate the adverse effects include:
      old age, volume -depleted state, pre-existing renal dysfunction and coexisting
      use of other nephrotoxins. Although it is impossible to present all the drugs
      causing renal disease, a few prototype drugs are mentioned. In a case of
      undiagnosed renal disease a possibility of drug-induced renal failure should be
      kept as the prompt removal of the drug and supportive management can reverse the
      renal dysfunction to a large extent.

PMID- 14719588
TI  - Parry Romberg syndrome: a close differential diagnosis of linear scleroderma en
      coup de sabre.

PMID- 14719589
TI  - Extensive syrinx with Charcot's joints.

PMID- 14719590
TI  - Metabolic syndrome X is common in Indians: but, why and how?
AB  - Metabolic syndrome X is common in Indians. But the exact cause for this is not
      clear. Earlier, I proposed that this could be due to low activities of delta6 and
      delta5 desaturases and consequent decreased plasma and tissue concentrations of
      long-chain polyunsaturated fatty acids of omega-6 and omega-3 series since
      perinatal period. This implies that perinatal to adult life supplementation of
      long-chain polyunsaturated fatty acids could prevent, arrest or postpone the
      development of metabolic syndrome X and its complications.

PMID- 14719591
TI  - Treatment of asymptomatic gallstones.

PMID- 14719592
TI  - Non-drug therapy in prevention and control of hypertension.
AB  - Non-drug therapy is a very vital aspect in prevention and treatment of
      hypertension. The successive reports of the Joint National Committee on
      Prevention, Detection, Evaluation and Treatment of Hypertension, WHO scientific
      report on primary prevention of essential hypertension and national High Blood
      Pressure Education Program's working groups report on primary prevention of
      hypertension have stressed on the non-drug therapy. Today a busy family physician
      does not spend enough time to explain to the patient various dietary and
      lifestyle modifications but straightaway prescribes the drugs. Every patient of
      hypertension from the stage of pre-hypertension to grade 2 hypertension should
      follow non-drug therapy. If non-drug therapy is strictly adhered, one can prevent
      cases of pre-hypertension from progressing to hypertension stage and one can
      reduce or stop the medications in Grade I (mild) hypertension. We have discussed
      the role of low salt, high potassium diet, role of caffeine intake, calcium and
      magnesium supplements, fish oil intake, cigarette smoking, alcohol consumption,
      role of physical exercise, stress reduction and bio-feedback, yoga, meditation
      and acupuncture. These recommendations regarding diet and lifestyle modifications
      should be targeted to population at large through public health authorities, non
      government organisations and news media.

PMID- 14719593
TI  - Oculopalatal syndrome with ataxia following hymenoptera sting.

PMID- 14719594
TI  - Nocardia asteroides mediastinitis complicating coronary artery bypass surgery.
AB  - A 63 years diabetic male was admitted with mediatinitis and sternal dehiscence.
      Nocardia asteroides sensu stricto Type VI was isolated from the mediastinal
      tissue and fluid during debridement. Prompt surgical intervention and treatment
      with ofloxacin both intravenously and later orally led to the cure.

PMID- 14719595
TI  - Trophoblastic hyperthyroidism.
AB  - Hyperthyroidism can occur secondary to gestational trophoblastic disease. The
      clinical and biochemical data of four women who had hyperthyroidism secondary to
      gestational trophoblastic disease was analyzed. The parity ranged from primi to
      gravida four and the period of amenorrhoea from six weeks to sixteen weeks. Three
      women had vomiting, two had bleeding per vaginum and two had tachycardia and
      minimal thyromegaly. The betahCG was more than 5,00,000 mlu/ml in all the cases.
      Three women required treatment for the hypermetabolic status and one woman had
      biochemical hyperthyroidism. Two of them had molar pregnancy, one had partial
      mole and one had persistent trophoblastic disease.

PMID- 14719596
TI  - Reversible leg ulcer due to hydroxyurea in a case of chronic myeloid leukemia.
AB  - The cutaneous side effects of hydroxyurea are lesser known complication of long
      term hydroxyurea therapy in myeloproliferative disorders. We report a non
      diabetic patient, who developed hydroxyurea dermopathy (leg ulcers) during long
      term treatment with hydroxyurea for chronic myeloid leukemia (CML). The time
      course of the development of ulcers and its healing suggests that these resulted
      from the direct toxicity of hydroxyurea. We aim to increase clinical awareness of
      this problem.

PMID- 14719597
TI  - Medical philately (medical personalities on stamps). Claude Bernard (1813-1878).

PMID- 14719598
TI  - Gross left ventricular voltage with preexcitation in isolated left ventricular
      non-compaction.
AB  - A 30 years man presented with symptoms of heart failure with prior history of
      pulmonary tuberculosis, on routine investigation he was found to have gross left
      ventricular voltage on the electrocardiogram and evidence of ventricular pre
      excitation. His echocardiogram confirmed the diagnosis of left ventricular non
      compaction. The aetiopathogenesis, clinical features, diagnostic criteria and
      review of literature of this rare entity is discussed here.

PMID- 14719599
TI  - Pacemaker endocarditis caused by Pseudomonas aeruginosa treated successfully.
AB  - Infective endocarditis (IE) is a rare but serious complication of permanent
      cardiac pacemaker placement. Endocarditis in the presence of prosthetic valves
      and pacemakers is usually due to staphylococci. We present a case of pacemaker
      endocarditis caused by Pseudomonas aeruginosa that was successfully treated with
      a combination of antimicrobial therapy and percutaneous removal of the colonized
      lead.

PMID- 14719600
TI  - Hypercalcemia induced by parathyroid hormone-related peptide after treatment of
      squamous cell carcinoma of oral cavity.
AB  - Squamous cell carcinoma of the head and neck is a rare cause of humoral
      hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the
      presenting symptoms of the disease. We report a case of squamous cell carcinoma
      of the oral cavity that presumably elaborated parathyroid hormone-related peptide
      (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.

PMID- 14719601
TI  - Hereditary spherocytosis in North India: need for more extensive data.

PMID- 14719603
TI  - Poetic voice of obstructive sleep apnea.

PMID- 14719602
TI  - Acinetobacter infection in Hickman's catheterized patient of multiple myeloma.

PMID- 14719604
TI  - Endobronchial metastases from renal cell carcinoma.

PMID- 14719605
TI  - Effect of lemon-honey in lukewarm water on hyperacidity.

PMID- 14719606
TI  - Gelatinous transformation of bone marrow.

PMID- 14719607
TI  - Setting calculations aside.

PMID- 14719608
TI  - Mammographic screening: does it work?

PMID- 14719609
TI  - Two angles on imaging.

PMID- 14719610
TI  - Risk communication: coping with imperfection.

PMID- 14719611
TI  - Multiple views: scrutinizing CT screening.

PMID- 14719612
TI  - Who should be screened?

PMID- 14719613
TI  - Treatment patterns for female breast cancer in Minnesota, 1995-1996.
AB  - Breast-conserving surgery (BCS) followed by radiation is an accepted alternative
      to mastectomy for treatment of early-stage breast cancer. This study evaluated
      age-group, geographic, and cancer-stage variables associated with the likelihood
      of receiving BCS or receiving mastectomy and the likelihood of receiving
      radiation therapy following BCS. Minnesota Cancer Surveillance System data on
      6,594 women diagnosed with breast cancer in Minnesota during the years 1995-1996
      were analyzed. Of those women who underwent breast cancer surgeries, 39% received
      BCS. Seventy-two percent of cases in which BCS was used were followed by
      radiotherapy. Women 65 years and older were less likely than younger women to
      receive BCS. Age and the stage of the cancer were independently associated with
      the likelihood of receiving radiation therapy following BCS. Breast cancer
      patients 75 years and older were 73% less likely to receive radiation following
      BCS than patients ages 40 to 49. Radiation following BCS was more likely among
      women in the Twin Cities metropolitan area and south central Minnesota than among
      women in other regions.

PMID- 14719614
TI  - Temporal and gender-related trends in brain metastases from lung and breast
      cancer.
AB  - Increased duration of cancer survival may allow a longer window for detection of
      metastases, including brain metastases. Using the entire population of Olmsted
      County, Minnesota, we looked at trends in the rate of brain metastases in people
      diagnosed with primary lung or breast cancers between January 1, 1988, and
      December 31, 2001. Yearly rates of brain metastases detection following the
      primary tumors were calculated from a combination of medical record and SEER
      database information. Trends in rates and gender differences were assessed. There
      was no discernible increase in the rates of brain metastases secondary to lung or
      breast cancer during the period of observation. However, women were twice as
      likely as men to have brain metastases detected following a primary lung cancer.
      This difference was constant over the time period. This twofold difference in
      brain metastases detected in women versus men with lung cancer deserves further
      evaluation and confirmation.

PMID- 14719615
TI  - A case of mistaken identity.

PMID- 14719616
TI  - Escitalopram-associated mania.

PMID- 14719617
TI  - Surgical support of Operation Sea Signal: adaptability of the 59th Air
      Transportable Hospital in Cuba.
AB  - OBJECTIVE: The attempted migration of approximately 50,000 Cubans in the summer
      of 1994 created a large patient population detained at Guantanamo Bay, Cuba. This
      study examined the roles and results of the 59th Air Transportable Hospital (ATH)
      in treating surgical problems within that population during Operation Sea Signal.
      METHODS: The surgical case log of the 59th ATH was used to identify all patients
      operated on at the 59th ATH during the interval of August 1994 to April 1995.
      These case records and the individual records of the three 59th ATH surgeons were
      used to determine the types of cases performed, complications, and outcomes.
      RESULTS: A total of 333 operations were performed at the 59th ATH in three types
      of surgery: (1) elective (267); (2) emergency for nonself-inflicted conditions
      (46); and (3) emergency for self-inflicted conditions (20). The total
      perioperative complication rate was 2.4% (8/333), and the wound infection rate
      for clean surgical cases was 0.87% (2/229). CONCLUSIONS: Elective surgery may be
      performed in a field environment with acceptable complication and wound infection
      rates. Humanitarian missions will be faced with considerable pathology from pre
      existing conditions within the population cared for. The humanitarian mission may
      be complicated by political situations that may encourage malingering and self
      injurious behavior within the population cared for. The latter events have not
      been previously encountered in humanitarian missions involving the U.S. military
      and must be considered by policy makers and mission planners in planning future
      humanitarian missions.

PMID- 14719618
TI  - Evaluation of stress debriefing interventions with military populations.
AB  - Military members are frequently exposed to traumatic events. In an attempt to
      mitigate the psychological impact of traumatic events, formal interventions, such
      as Critical Incident Stress Debriefing and Process Debriefing, have been
      developed and implemented. Through a literature review of psychological
      debriefing interventions in the military, several anecdotal and research-based
      observations are discussed. Suggestions for clinical application and programmatic
      research are made based on these empirical findings.

PMID- 14719619
TI  - The magazine: a major cause of bullet fragmentation.
AB  - The fragmentation impact of high-velocity bullets penetrating the body after
      piercing through the magazines carried by soldiers was investigated
      experimentally. In this study, 16 pigs and 7.62x51-mm full metal jacket bullets
      were used. Pigs were assigned into two groups, and within 5 minutes of their
      being sacrificed with overdose anesthesia, bullets were fired into the first
      group on which magazines were placed and into the second group on which magazines
      were not placed, targeting abdominal left lower quadrant. It was found that in
      pigs not carrying magazines, all bullets pierced through the pig; bullets were
      not fragmented. However, in pigs with magazines, common fragmentation in bullets
      and multiple organ perforations occurred. It was concluded that magazines caused
      the bullets to be fragmented, increasing tissue and organ damage.

PMID- 14719620
TI  - Overview of overseas humanitarian, disaster, and civic aid programs.
AB  - The U.S. Department of Defense (DoD) conducts humanitarian assistance missions
      under the Overseas Humanitarian Disaster and Civic Aid program for the statutory
      purposes of training military personnel, serving the political interests of the
      host nation and United States, and providing humanitarian relief to foreign
      civilians. These purposes are undertaken via the humanitarian assistance (HA),
      humanitarian and civic assistance, and excess property donation programs. DoD
      conducts over 200 such projects annually at a direct cost of approximately 27
      million dollars in fiscal year 2001. Although varying by year and command, as
      many as one-half of these projects involve aspects of health care. These range
      from short-term patient care to donation of medical supplies and equipment excess
      to the needs of the DoD. Despite the considerable resources invested and
      importance of international actions, there is presently no formal evaluation
      system for these HA projects. Current administrative staffing of these programs
      by military personnel is often by individuals with many other duties and
      responsibilities. As a result, humanitarian projects are often inadequately
      coordinated with nongovernmental organizations, private volunteer organizations,
      or host-nation officials. Nonmedical military personnel sometimes plan health
      related projects with little or no coordination with medical experts, military or
      civilian. After action reports (AARs) on these humanitarian projects are often
      subjective, lack quantitative details, and are devoid of measures of
      effectiveness. AARs are sometimes inconsistently completed, and there is no
      central repository of information for analysis of lessons learned. (The
      approximate 100 AARs used in the conduct of these studies are available for
      official use in the Learning Resources Center, Uniformed Services University of
      Health Sciences.) Feedback from past humanitarian projects is rare and with few
      exceptions; DoD-centric projects of a similar design are often repeated. Critical
      reviews to determine whether other kinds of projects might be more effective are
      rarely conducted. Recommendations for improving the effectiveness of DoD HA under
      Overseas Humanitarian Disaster and Civic Aid programs include: ensuring adequate
      staffing to meet the complex, dynamic nature of humanitarian missions and
      measuring the effectiveness of each project in mandatory, standardized AARs. For
      medical HA projects, application of public health strategies would compliment the
      patient care approach of the majority of medical projects to date. This offers
      possibilities for enhancing host nation infrastructure, allowing improvements
      beyond the short period of most military humanitarian projects.

PMID- 14719621
TI  - The impact of a nursing triage line on the use of emergency department services
      in a military hospital.
AB  - The purpose of this study was to evaluate the impact of nursing telephone triage
      on the appropriateness of emergency department (ED) use among 563 patients at a
      military hospital by comparing 286 ED patients referred by the Tel-a-Nurse Line
      (TAN) with 277 non-TAN-referred patients from October 2000 to November 2000. When
      controlling for confounding factors, TAN-referred patients had less appropriate
      ED use than non-TAN-referred patients, although this was not statistically
      significant (odds ratio = 0.87, p = 0.452). After excluding TAN patients with a
      primary clinic disposition but who were directed to the ED because no clinic
      appointments were available, TAN-referred patients had more appropriate referrals
      than non-TAN patients, although this was also not significant (odds ratio = 1.19,
      p = 0.401). TAN patients directed to the ED because of clinic appointment
      unavailability contributed significantly to inappropriate ED use with 62% having
      low acuity. This finding underscores the need to evaluate clinic availability for
      the TAN line and possibly for all patients as well.

PMID- 14719622
TI  - Walter Reed Army Medical Center's Internet-based electronic health portal.
AB  - BACKGROUND: Use of the World Wide Web (WWW) and electronic media to facilitate
      medical care has been the subject of many reports in the popular press. However,
      few reports have documented the results of implementing electronic health portals
      for essential medical tasks, such as prescription refills and appointments.
      METHODS: At Walter Reed Army Medical Center, "Search & Learn" medical
      information, Internet-based prescription refills and patient appointments were
      established in January 2001. A multiphase retrospective analysis was conducted to
      determine the use of the "Search & Learn" medical information and the relative
      number of prescription refills and appointments conducted via the WWW compared
      with conventional methods. RESULTS: From January 2001 to May 2002, there were
      34,741 refills and 819 appointments made over the Internet compared with
      2,275,112 refills and approximately 500,000 appointments made conventionally. WWW
      activity accounted for 1.52% of refills and 0.16% of appointments. There was a
      steady increase in this percentage over the time of the analysis. In April of
      2002, the monthly average of online refills had risen to 4.57% and online
      appointments were at 0.27%. Online refills were projected to account for 10% of
      all prescriptions in 2 years. The "Search & Learn" medical information portion of
      our web site received 147,429 unique visits during this same time frame, which
      was an average of 326 visitors per day. CONCLUSIONS: WWW-based methods of
      conducting essential medical tasks accounted for a small but rapidly increasing
      percentage of total activity at Walter Reed Army Medical Center. Subsequent
      phases of analysis will assess demographic and geographic factors and aid in the
      design of future systems to increase use of the Internet-based systems.

PMID- 14719623
TI  - Health practices of male Department of Defense health care beneficiaries: a
      follow-up on prostate cancer screening in the national capital area.
AB  - The purpose of this study was to assess screening for prostate cancer (PC) of
      male Department of Defense health care beneficiaries in the national capital
      area. This study was a follow-up of a previous research of African-American men's
      PC screening practices. In the previous study, 85% of African-American men
      screened for PC and the determinants of screening were men's perceived "benefits"
      of PC testing, age, and education. This follow-up study was conducted on 234 men
      age 52 years and over regardless of ethnicity using a questionnaire and
      convenience sampling similar to the prior study. Results showed 96% screened for
      PC; no statistical differences in PC screening and ethnicity; and men's perceived
      "self-efficacy" and "benefits" were predictors of PC screening. More men screened
      for PC when advised by their health care providers and 94% of men stated "trust"
      in health care providers, indicating the importance of a "trusting-informative
      health care milieu" for men's self-efficacy to screen for PC.

PMID- 14719624
TI  - Nutrition knowledge and supplement use among elite U.S. army soldiers.
AB  - A U.S. Army Special Forces (SF) unit was studied to determine characteristics of
      supplement users, assess nutrition knowledge, and identify nutrition information
      sources. SF-qualified (n = 119) and non-SF, support soldiers (n = 38)
      participated. Most soldiers (87%) reported current supplement use with more SF
      (90%) than non-SF, support soldiers (76%) using supplements (p < or = 0.05).
      Supplements SF reported using most were multivitamins, sports bars/drinks, and
      vitamin C. The mean nutrition knowledge score for all soldiers was 48.5 +/- 15.2%
      correct responses. Most soldiers incorrectly believe protein is used for energy
      for short-term athletic events (64%) and that vitamins provide energy (58%). The
      most common information sources reportedly used were popular magazines/books
      (75%), friends/teammates (55%), physicians/nurses, radio/television (34%), and
      the Internet (31%).

PMID- 14719625
TI  - Military aviators, special operations forces, and causal malaria prophylaxis.
AB  - U.S. military aviators are currently restricted to the use of chloroquine or
      doxycycline for malaria prophylaxis. Ground forces are allowed the additional
      option of taking mefloquine. These medications are begun before deployment, must
      be taken for 4 weeks after leaving the malarious area, and primaquine must be
      added to the regimen the last 2 of those 4 weeks. Compliance with this regimen is
      often poor, especially in populations who travel abroad frequently for short
      periods of time. Causal malaria prophylaxis offers potential benefits of
      decreased length of postdeployment regimens and obviates the need for a second
      medication for terminal prophylaxis. Potential obstacles include adverse drug
      reactions, cost, and rapid development of resistance to new medications by
      Plasmodium species, which should be weighed against the risks to health and
      mission success in each deployment.

PMID- 14719626
TI  - The quality of groundwater for certain chemicals in military fields in Ankara.
AB  - OBJECTIVE: The goal of this study was to determine the quality of groundwater for
      certain chemicals from all wells for the military units in Ankara (the capital
      city of Turkey) to evaluate special situations like a nuclear, biological, and
      chemical attack. METHOD: The quality of underground water has been evaluated
      chemically by examining 34 different water specimens. Various chemical parameters
      and heavy metals have been assessed in these samples by using an ion meter and
      atomic absorption spectrophotometer. RESULTS: Nitrate and chloride have been
      assessed at a higher rate with the levels exceeding maximum contaminant levels.
      Mercury, arsenic, aluminum, iron, conductivity, and salinity have also had levels
      exceeding maximum contaminant levels for each of them according to the levels set
      by the World Health Organization. CONCLUSION: This study has given us some
      powerful clues that underground water in Ankara is at a growing risk to be
      contaminated mainly with nitrate and chloride. Although more detailed
      investigations are necessary for a better evaluation, it is clear that preventive
      measures should be implemented or improved.

PMID- 14719627
TI  - Lyme disease reporting for Navy and Marine Corps (1997-2000).
AB  - Reported cases of Lyme disease for Navy and Marine Corps personnel during 1997
      2000 are presented from data collected in the Naval Disease Reporting System and
      the Defense Medical Epidemiological Database. Naval Disease Reporting System
      identified 210 case subjects; 60% were men, 49% were family members, and 37% were
      active duty, and most originated in the second quarter of the calendar year.
      States reporting the greatest number of reports were Connecticut (44%), North
      Carolina (16%), Rhode Island (10%), and Virginia (10%), which was generally
      consistent with national figures and the concentration of military populations.
      Incidence rates from Defense Medical Epidemiological Database for Lyme disease
      were generally higher for active duty personnel than reported civilian rates.
      Areas for improvement for Naval Disease Reporting System are identified and
      include additional emphasis on complete reporting on patient history and on Lyme
      disease antibody testing results. These findings suggest that Lyme disease is an
      important disease in military medicine, particularly in the eastern United
      States.

PMID- 14719628
TI  - Human leukocyte antigens in Gulf War veterans with chronic unexplained multiple
      symptoms.
AB  - Several articles have suggested that immune dysregulation related to Gulf War
      deployment may be involved in chronic illnesses with an unclear etiology among
      Gulf War veterans. To determine whether genetic susceptibility related to the
      human leukocyte antigen (HLA) system might play a role in development of the
      veterans' illnesses, we examined the frequency distribution of HLA A, B, DR, and
      DQ antigens from symptomatic veterans residing in south-central Pennsylvania
      compared with a local healthy population database. Only HLA-A28 demonstrated
      statistical significance. A28 was present in 7 (21.9%) of 32 of the veterans and
      15 (6.9%) of 217 of the healthy population (p = 0.01, Fisher's exact test). This
      accounts for a minority of the ill veterans tested and is not statistically
      significant when corrected for the number of antigens determined. We conclude
      that specific HLA antigens are not strongly associated with the illnesses of Gulf
      War veterans.

PMID- 14719629
TI  - Geographic mobility, family, and maternal variables as related to the
      psychosocial adjustment of military children.
AB  - The present study examined maternal and family factors and family mobility as
      related to mothers' and children's reports of the psychological adjustment of
      children in military families. Participants were 86 mother-child dyads in U.S.
      traditional military families. Children's reports of loneliness, peer
      relationships, fear of negative evaluations, and self-esteem were predicted by
      family cohesiveness, children's reports of their relationships with their
      mothers, and the length of time they had lived in their current residence, but
      not their rate of mobility (i.e., number of moves in the child's lifetime divided
      by the child's age). In contrast, maternal depressive symptoms predicted
      children's depressive and anxious behaviors, and both maternal depressive
      symptoms and children's perception of their relationship with their mothers
      predicted children's aggression and noncompliance. Results suggest that moving
      may not be as important as other aspects of maternal functioning and family
      relationships for the psychosocial adjustment of children in military families.

PMID- 14719630
TI  - Wechsler Adult Intelligence Scale-third edition characteristics of a military
      traumatic brain injury sample.
AB  - This article describes the postinjury cognitive functioning of a sample of active
      duty, retired, and military beneficiaries who received traumatic brain injuries.
      Patients were seen in the neuropsychology clinic at Brooke Army Medical Center
      for a detailed cognitive and personality assessment. The scores on a major
      component of this evaluation, the Wechsler Adult Intelligence Scale, third
      edition, are summarized. The results are compared with those reported in the
      Wechsler Adult Intelligence Scale, third edition technical manual for a smaller,
      less diverse sample. The findings are consistent with the formulation that stable
      verbal skills are most resistant to brain injury, followed by nonverbal reasoning
      and visuospatial ability, and then working memory with speed of information
      processing being the most vulnerable to the effects of brain injury.

PMID- 14719631
TI  - Comparing patients' and physicians' opinions on quality outpatient care.
AB  - The objective of this study was to compare the opinions of patients and
      physicians on the importance of discrete elements of health care as determinants
      of the quality of outpatient care. A survey was conducted on patients and
      physicians of a military hospital in Ankara, Turkey. Participants rated 60
      elements of care on its importance to high-quality care on a 5-point scale (not
      important [1] to essential [5]). These elements covered eight domains: physician
      clinical skill, physician interpersonal skill, outpatient clinic support staff,
      outpatient clinic environment, provision of health-related information, patient
      involvement in care, access to care, and coordination of care. Patients and
      physicians agreed that clinical skill and interpersonal skill of the physician
      are the most crucial elements of quality health care, but they disagreed about
      the relative importance of access to care, coordination of care, and provision of
      information. Patients placed greater value on these domains than did physicians.

PMID- 14719632
TI  - Immune and hormonal changes following intense military training.
AB  - This study was designed to determine whether the immune and hormonal systems were
      affected by a 5-day military course following 3 weeks of combat training in a
      population of 26 male soldiers (mean age, 21 +/- 2 years). The combination of
      continuous heavy physical activity and sleep deprivation led to energy
      deficiency. At the beginning of the training program and immediately after the
      combat course, saliva samples were assayed for secretory immunoglobulin A and
      plasma samples were assayed for interleukin-6, dehydroepiandrosterone sulfate,
      prolactin, catecholamines, glucocorticoids, and testosterone. Secretory
      immunoglobulin A was lower and circulating interleukin-6 was increased by the end
      of the course, which was attributed to sympathoadrenergic stimulation.
      Dehydroepiandrosterone sulfate, prolactin, and testosterone levels fell
      significantly. These results suggest that prolonged and repeated exercise such as
      that encountered in a military training program induces immune impairment via a
      decrease in mucosal immunity and a release of interleukin-6 into the circulation.
      The impaired secretion of dehydroepiandrosterone sulfate and prolactin, two
      immunomodulatory hormones, was thought to be a response to the chronic stressors.
      Lowered testosterone reflects a general decrease in steroid synthesis as a
      consequence of the physical and psychological strain.

PMID- 14719633
TI  - Respiratory illnesses in relation to military assignments in the Mojave Desert:
      retrospective surveillance over a 10-year period.
AB  - Military training exercises are conducted routinely in the Mojave Desert. To
      determine whether assignment in this desert environment increases risk of
      respiratory illnesses, hospitalization rates were compared between two matched
      cohorts of soldiers during three intervals of follow-up during a 10-year
      surveillance period. The exposed cohort (N = 21,543) included all soldiers who
      were ever assigned to the Mojave Desert during the surveillance period. The
      control cohort (N = 86,172) included soldiers matched on demographic
      characteristics who were never assigned to the Mojave Desert during the
      surveillance period. Three follow-up intervals ("before," "during," "after") were
      defined relative to times when exposed soldiers were assigned to the desert.
      Rates of respiratory hospitalizations were similar between the cohorts for the
      "before" and "during" intervals but were higher in the exposed cohort for the
      "after" interval (rate ratio, 1.30; 95% confidence interval, 1.07-1.59). This
      difference was largely attributable to excess pneumonia and influenza
      hospitalizations in the exposed cohort. Healthy, young adults may have increased
      susceptibility to respiratory infectious illnesses after prolonged exposures to
      desert environments.

PMID- 14719634
TI  - Civil War Federal Navy physicians.
AB  - The Federal Navy's Bureau of Medicine and Surgery experienced a substantial loss
      of officers during 1861. It responded to the loss and the increased demand for
      its services by augmenting its regular medical officers with volunteer
      physicians. The medical corps more than doubled in size between 1861 and 1865 as
      a result of the recruiting efforts. Navy physicians were involved in blockade
      duty, anticommerce raider cruises, amphibious assaults, riverine duty, and
      staffing naval facilities ashore. Their services are virtually unknown despite
      their involvement in most naval activity during the war. This article illuminates
      their efforts. It does so by analyzing individual service records and reports
      compiled in the Official Records of the Union and Confederate Navies during the
      War of the Rebellion. The Bureau of Medicine and Surgery successfully met the
      demands made upon it during the American Civil War.

PMID- 14719635
TI  - Community violence as it affects child development: issues of definition.
AB  - The state of the art of definition of community violence as it relates to child
      development was examined in terms of the definitions used in 23 empirical
      studies. In all cases community violence was defined in terms of what were
      assumed to be measurements obtained as linear combinations of a priori numerical
      weighting of responses to questions--asked either of a child or of the parent of
      a child--about experiencing and/or witnessing and/or hearing about instances of
      violence. Thus, the definitions can be seen to represent the perspectives of 2
      kinds of observers--the child or the child's parent--and 3 levels of closeness to
      violence--experiencing, witnessing, or hearing about violence. Combining these
      perspectives and levels, the following 8 different definitions could be seen to
      be used in the practice of 1 or more of the 23 empirical studies: Child Self
      Report (perception) of either (1) experiencing, or (2) witnessing, or (3)
      experiencing and witnessing, and hearing about violence; or Parent Report
      (perception) of the Child (4) experiencing, or (5) witnessing, or (6)
      experiencing and witnessing and hearing about violence, or (7) = (1) + (4), or
      (8) = (3) + (6). In almost all the examples of research definitions it was
      assumed implicitly and without test of the assumption that different violent
      events were interchangeable, and usually it was assumed (again without test) that
      the magnitudes of different violence events were equal. Usually, an unstated
      theory of stress appeared to guide the measurement definition, but in one study
      definitions were developed and tested in terms of a clearly-stated theory of
      learning. It was concluded that definition of community violence is a measurement
      problem; that very likely it is multidimensional; that it could be more nearly
      solved if better attention were given to specifying it in terms of theory that
      can be put to test and by attending to basic assumptions and principles of
      measurement.

PMID- 14719636
TI  - Children exposed to war/terrorism.
AB  - This paper reviews the prevalence of psychological morbidities in children who
      have been exposed to war-related traumas or terrorism as well as the diversity of
      war-related casualties and their associated psychological responses. The
      psychological responses to war-related stressors are categorized as (1) little or
      no reaction, (2) acute emotional and behavioral effects, and (3) long-term
      effects. Specific categories of war-related casualties discussed include refugee
      status, traumatic bereavement, effects of parental absence, and child soldiers.
      Psychological responses associated with terrorism and bioterrorism are presented.
      Lastly, mediators of the psychological response to war-related stressors are
      discussed, to include exposure effects, gender effects, parental, family and
      social factors, and child-specific factors. Children exposed to war-related
      stressors experience a spectrum of psychological morbidities including
      posttraumatic stress symptomatology, mood disorders, externalizing and disruptive
      behaviors, and somatic symptoms determined by exposure dose effect. Specific
      questions for future research are identified.

PMID- 14719637
TI  - Prevalence of child and adolescent exposure to community violence.
AB  - Emerging as one of the most significant health issues facing American youth
      today, child and adolescent exposure to community violence has generated much
      interest across multiple disciplines. Most research to date has focused on
      documenting the prevalence of community violence and the emotional and behavioral
      ramifications. This paper provides an overview of the current literature
      regarding prevalence of youth exposure to community violence, and identifies
      those areas where further research is warranted. In addition to examining overall
      rates of community violence exposure, this paper reviews the prevalence of
      different types of community violence, such as weapon use, physical aggression,
      and crime-related events. Predictors of community violence exposure, including
      gender, age, race, socioeconomic status, behavior patterns, and geography, are
      discussed.

PMID- 14719638
TI  - Consequences of children's exposure to community violence.
AB  - Much has been learned over the past decade about the way children respond to
      experiences of violence in their community. The goal of this paper is to review
      what is known about the effects of community violence on children's development.
      In addition to main effects, factors that mediate these effects, as well as
      factors that moderate children's response to community violence are discussed.
      Special attention is paid to developmental differences in children's responses to
      community violence and the factors that may promote resilient functioning.

PMID- 14719639
TI  - Consequences of child exposure to war and terrorism.
AB  - Acts of war and terrorism are increasingly prevalent in contemporary society.
      Throughout history, weaponry has become more efficient, accurate, and powerful,
      resulting in more devastation and loss of human life. Children are often
      overlooked as victims of such violence. Around the world, children are exposed to
      violence in multiple forms, frequently developing traumatic stress reactions.
      Such reactions are best understood within the context of social-emotional and
      cognitive development, as children respond differently to the stress of violence
      depending on their developmental level. Furthermore, the violence of war and
      terrorism often results in a multitiered cascade of negative life events
      including loss of loved ones, displacement, lack of educational structure, and
      drastic changes in daily routine and community values. These numerous losses,
      challenges, and stresses affect children's brains, minds, and bodies in an
      orchestrated whole-organism response. This paper describes these effects,
      synthesizing the current state of research on childhood traumatic stress
      reactions from the fields of neuroscience, clinical psychology, and pediatric
      diagnostic epidemiology.

PMID- 14719640
TI  - Children exposed to community violence: the rationale for early intervention.
AB  - Children are exposed to violence in their homes and communities at
      extraordinarily high rates. Given the alarming rates of exposure and its known
      impact on child developmental outcomes, crisis intervention geared at
      interrupting the negative effects of violence exposure are increasingly
      important. This review provides a rationale for the implementation of early and
      crisis intervention strategies for children exposed to community violence and
      recommends principles for applying these interventions. These principles are
      based on the body of research concerning risk and protective factors for children
      who have been exposed to violence. Relevant factors are reviewed and recommended
      principles are explicated that correlate to these factors. Issues concerning
      developmentally informed crisis intervention, support of parental executive
      functioning, and the need for active community partnership to help ameliorate
      risk factors are highlighted.

PMID- 14719641
TI  - Next steps in research on children exposed to community violence or
      war/terrorism.
AB  - The articles in this special issue of Clinical Child and Family Psychology Review
      provide an overview of what is known about children's exposure to community
      violence and war/ terrorism, and indicate significant gaps in extant research.
      These gaps and research needs are summarized in this conclusion.

PMID- 14719642
TI  - Fano resonances in prism-coupled square micropillars.
AB  - We report Fano resonances in the frustrated total internal reflection (TIR)
      spectra of a prism-coupled square micropillar. Our angle-selective frustrated TIR
      technique reveals characteristically asymmetric resonance line shapes, which
      evolve spectrally over approximately a 2pi phase in the far field within a
      subdegree range of reflection angles. We theoretically model the asymmetric line
      shapes by the interference between a high-Q resonance that is evanescently
      coupled and partially confined by TIR, and a coherent background that is total
      internally reflected at the prism surface without coupling to the micropillar.

PMID- 14719643
TI  - Whispering-gallery-bottle microcavities: the three-dimensional etalon.
AB  - In a tapered optical fiber there exist localized light structures that, in
      analogy to the magnetic bottles used in plasma fusion, can be called whispering
      gallery bottles (WGBs). These essentially three-dimensional structures are formed
      by the spiral rays that experience total internal reflection at the fiber surface
      and that also bounce along the fiber axis in response to reflection from the
      regions of tapering. It is shown that the Wentzel-Kramers-Brillouin quantization
      rules for the strongly prolate WGBs can be inversed exactly, thus determining the
      cavity shape from its spectrum. The approximation considered allows one to find
      the shape of the etalon bottle, which, similar to the one-dimensional Fabry-Perot
      etalon, contains an unlimited number of equally spaced wave-number eigenvalues.
      The problem of determining such a non-one-dimensional cavity is not trivial,
      because such a cavity does not exist among the uniformly filled cavities such as
      rectangular boxes, cylinders, and spheroids that allow separation of variables.
      The etalon cavity corresponds to the fiber radius variation p(z) =
      rho0/cos(deltakz)/, where deltak is the wave-number spacing. The latter result is
      in excellent agreement with ray-dynamics numerical modeling.

PMID- 14719644
TI  - Hadamard speckle contrast reduction.
AB  - The condition for a diffuser to produce the maximum speckle contrast reduction
      with the minimum number of distinct phase patterns is derived. A binary
      realization of this optimum diffuser is obtained by mapping the rows or columns
      of a Hadamard matrix to the phase patterns. The method is experimentally verified
      in the Grating Light Valve laser projection display.

PMID- 14719645
TI  - Birefringence-induced splitting of the zero-dispersion wavelength in nonlinear
      photonic crystal fibers.
AB  - We investigate how the strongly wavelength-dependent birefringence in nonlinear
      photonic crystal fibers leads to a splitting in the zero-dispersion wavelength
      for the two polarizations. We translate the requirements for the maximum
      splitting of the zero-dispersion wavelength to requirements for transverse
      structural uniformity by adopting a simple effective-index approach in which the
      birefringence is calculated in a step-index fiber with an elliptical core. We
      find that to reduce the splitting to less than 1 nm the birefringence should be
      less than 2 x 10(-5), resulting in a transverse uniformity requirement of 1-3%,
      depending on the index step from the core to the cladding.

PMID- 14719646
TI  - Temperature dependence of Brillouin frequency, power, and bandwidth in panda, bow
      tie, and tiger polarization-maintaining fibers.
AB  - We report a study of the temperature dependence of the Brillouin gain and loss
      for three different kinds of commercial polarization-maintaining fibers for the
      first time to our knowledge. The Brillouin frequency differences between the fast
      and slow axes are independent of the temperature, varying between 2.9 and 4.3
      MHz. Using 2-ns pulses (equivalent to a spatial resolution of 20 cm), we find
      that the temperature coefficients for the relative Brillouin power at a
      wavelength of 1310 nm are 0.26%/degrees C (panda fiber), 0.23%/degrees C (bow-tie
      fiber), and 0.04%/degrees C (tiger fiber); the temperature coefficients for the
      Brillouin frequency are 1.37 MHz/degrees C (panda), 1.66 MHz/degrees C (tiger),
      and 2.30 MHz/degrees C (bow-tie). The temperature coefficients for the Brillouin
      gain bandwidth are 0.15 MHz/degrees C (panda), 0.20 MHz/degrees C (bow-tie), and
      0.22 MHz/degrees C (tiger).

PMID- 14719647
TI  - Microstructured optical fiber for single-polarization air guidance.
AB  - An air-core microstructured fiber design that supports a single-polarization,
      circularly symmetric nondegenerate mode is presented. The fiber design is modeled
      directly, and the microstructured cladding is analyzed by use of band diagrams to
      elucidate the mechanism through which polarization nondegeneracy is achieved.

PMID- 14719648
TI  - Efficient iterative technique for designing Bragg gratings.
AB  - We present a new iterative method for designing Bragg gratings based on the
      Levenberg-Marquardt method of minimizing a chi-squared merit function. It is
      effective for designing both weak and strong gratings and is particularly well
      suited for unchirped gratings.

PMID- 14719649
TI  - Comparison of the methods for discriminating temperature and strain in
      spontaneous Brillouin-based distributed sensors.
AB  - A recently proposed method of measuring the two Brillouin frequencies in a
      multicompositional fiber core for unambiguously resolving temperature and strain
      in a distributed sensor is compared with the previously established technique of
      measuring the intensity and frequency of the single Brillouin peak in a standard
      single-mode fiber.

PMID- 14719650
TI  - Thermally tunable narrow-bandpass filter based on a linearly chirped fiber Bragg
      grating.
AB  - We propose a new method for the development of a tunable optical bandpass filter
      (TOBF) based on a linearly chirped fiber Bragg grating (LCFBG). A NiCr wire
      heater is used to heat the LCFBG at a small point to introduce a narrow passband
      within the stop band of the LCFBG. The central wavelength of the passband is
      tuned by scanning the wire heater along the LCFBG. As an example demonstrating
      the effectiveness of the proposed method, we demonstrate a TOBF with a very small
      3-dB bandwidth of approximately 7 pm, a tuning range of 16.4 nm, and a rejection
      ratio of more than 25 dB. Compared with previously reported tunable-fiber-based
      bandpass filters, this method provides the advantages of a large tuning range,
      continuous tunability, a switchable passband, a simple tuning mechanism, low
      cost, and narrow bandwidth.

PMID- 14719651
TI  - Analysis of circular fibers with an arbitrary index profile by the Galerkin
      method.
AB  - We propose a full-vectorial Galerkin method for the analysis of circular
      symmetric fibers with arbitrary index profiles. A set of orthogonal Laguerre
      Gauss functions is used to calculate the dispersion relation and mode fields of
      TE and TM modes. Examples are given for both standard step-index fibers and Bragg
      fibers. For standard step-index fiber with low or high index contrast, the
      Galerkin method agrees well with the analytical results. In the case of the TE
      mode of a Bragg fiber it agrees well with the asymptotic results.

PMID- 14719652
TI  - Reduction of the phase jitter in differential phase-shift-keying soliton
      transmission systems by in-line Butterworth filters.
AB  - We examine reduction of phase jitter by use of in-line Butterworth filters in
      soliton systems in the context of differential phase-shift-keying coding. We also
      demonstrate numerically that the use of a Butterworth filter in a return-to-zero
      differential phase-shift-keying system can reduce continuum background radiation.

PMID- 14719653
TI  - Characterizations at high temperatures of long-period gratings written in
      germanium-free air-silica microstructure fiber.
AB  - We report what is to our knowledge the first characterization at high
      temperatures of long-period fiber gratings written in Ge-free air-silica
      microstructure fiber. The gratings written with the electric-arc technique suffer
      a low shift of the resonance wavelengths when the temperature is increased from
      20 degrees C to 1200 degrees C. This shift is studied and compared with that of a
      long-period fiber grating written in a standard single-mode fiber by the same
      technique. Good thermal stability of the grating and of the fiber after annealing
      at 1200 degrees C for 1 h is demonstrated.

PMID- 14719654
TI  - Phase-resolved second-harmonic imaging with nonideal laser sources.
AB  - An interferometric imaging setup is described that allows us to map the spatial
      distribution of the phase of a second-harmonic (SH) wave by using multimode laser
      sources with achromatic beam imaging of the fundamental and SH waves. Working
      distances > 1 m and a robust setup allow experiments that were not possible
      before.

PMID- 14719655
TI  - Parabolic nondiffracting optical wave fields.
AB  - We demonstrate the existence of parabolic beams that constitute the last member
      of the family of fundamental nondiffracting wave fields and determine their
      associated angular spectrum. Their transverse structure is described by parabolic
      cylinder functions, and contrary to Bessel or Mathieu beams their eigenvalue
      spectrum is continuous. Any nondiffracting beam can be constructed as a
      superposition of parabolic beams, since they form a complete orthogonal set of
      solutions of the Helmholtz equation. A novel class of traveling parabolic waves
      is also introduced for the first time.

PMID- 14719656
TI  - Open- and closed-loop aberration correction by use of a quadrature
      interferometric wave-front sensor.
AB  - Experimental results are presented for an adaptive optics system based on a
      quadrature Twyman-Green interferometric wave-front sensor. The system uses a
      circularly polarized reference beam to form two interferograms with a pi/2 phase
      shift. The experiments conducted used Kolmogorov phase screens to simulate
      atmospheric phase distortions. Strehl ratio improvements by a factor of 8, to an
      absolute value of 0.45, are demonstrated.

PMID- 14719657
TI  - Dispersion-based optical routing in photonic crystals.
AB  - We present and experimentally validate self-collimation in planar photonic
      crystals as a new means of achieving structureless confinement of light in
      optical devices. We demonstrate the ability to arbitrarily route light by
      exploiting the dispersive characteristics of the photonic crystal. Propagation
      loss as low as 2.17 dB/mm is observed, and proposed applications of these devices
      are presented.

PMID- 14719658
TI  - Waveguiding effects in self-pulsing vertical-cavity surface-emitting lasers.
AB  - Self-pulsing in semiconductor lasers containing a saturable absorber is well
      documented. We propose an alternative mechanism leading to self-pulsing in
      vertical-cavity surface-emitting lasers. We specifically consider waveguiding
      effects and determine the conditions for self-pulsing. Our theoretical and
      numerical results agree with experimental observations reported by Willemsen et
      al. [Appl. Phys. Lett. 77, 3514 (2000)].

PMID- 14719659
TI  - High-brightness 2.4-W continuous-wave Nd:GdVO4 laser at 670 nm.
AB  - We report on a diode-pumped 1.3-microm Nd:GdVO4 cw laser, intracavity doubled for
      highly efficient generation of red light. We obtained as much as 2.4 W of power
      at 670 nm (corresponding to 26% optical-to-optical efficiency) in a nearly TEM00
      mode and with small amplitude noise. To the best of our knowledge, these results
      represent the highest performance at this wavelength for cw solid-state lasers.

PMID- 14719660
TI  - Excited-state absorption and 1064-nm end-pumped laser emission of Nd:YVO4 single
      crystal fiber grown by laser-heated pedestal growth.
AB  - We present an investigation of the excited-state absorption and laser emission of
      a 1.0-at. %-Nd3+-doped YVO4 single-crystal fiber grown by the low-cost and
      versatile laser-heated pedestal growth technique. Efficient laser emission at
      1064 nm was achieved when the fiber was pumped, in an end-pump cavity, by a
      Ti:sapphire laser at 808 nm. A continuous-wave threshold of 10 mW was observed
      with an efficiency of 42% with respect to the absorbed pump power and the maximum
      output power of 200 mW. These results are excellent when compared with those of a
      commercial bulk crystal adapted to the same cavity (48% efficiency, 250-mW
      maximum output power). Thus the fibers are characterized as strong candidates for
      the construction of compact lasers that can also be pumped by low-cost diode
      lasers.

PMID- 14719661
TI  - Highly efficient second-harmonic nanosource for near-field optics and microscopy.
AB  - A nanometric source of second-harmonic (SH) light with unprecedented efficiency
      is demonstrated; it exploits the grazing-incidence illumination of a metal tip,
      which is conventionally used for atomic force microscopy, by 25-fs laser pulses
      of a high-energy Ti:sapphire oscillator. Tip scanning around the beam focus shows
      that the SH generation is strongly localized at its apex. The polarization
      dependence of the SH light complies with the model of an on-axis nonlinear
      oscillating dipole.

PMID- 14719662
TI  - Random-wavelength solid-state laser.
AB  - The spectral properties of a diode-pumped Yb:Y2O3 ceramic laser are reported. We
      show experimentally that the instantaneous emission wavelengths of the laser
      change randomly with time, whereas its emission has fixed well-defined transverse
      modes. The central wavelength of the laser emission also shifts prominently with
      the increase of intracavity light intensity. It is found that the spectral
      properties of the laser can be explained well based on the strong reabsorption of
      light in the gain medium.

PMID- 14719663
TI  - Time-dependent speckle in holographic optical coherence imaging and the health of
      tumor tissue.
AB  - Holographic optical coherence imaging acquires en face images from successive
      depths inside scattering tissue. In a study of multicellular tumor spheroids the
      holographic features recorded from a fixed depth are observed to be time
      dependent, and they may be classified as variable or persistent. The ratio of
      variable to persistent features, as well as speckle correlation times, provides
      quantitative measures of the health of the tissue. Studies of rat osteogenic
      sarcoma tumor spheroids that have been subjected to metabolic and cross
      polymerizing poisons provide quantitative differentiation among healthy,
      necrotic, and poisoned tissue. Organelle motility in healthy tissue appears as
      super-Brownian laser speckle, whereas chemically fixed tissue exhibits static
      speckle.

PMID- 14719664
TI  - In vivo fluorescence microscopy of neuronal activity in three dimensions by use
      of voltage-sensitive dyes.
AB  - We report in vivo imaging of neuronal electrical activity from superficial layers
      of the mouse barrel cortex. The measurements have approximately 16-microm spatial
      and 3-ms temporal resolution and reach depths of 150 microm below the cortical
      surface. The depth-dependent differential-fluorescence optical sections of
      activity are consistent with known cortical architecture and represent an
      important step toward in vivo measurement of functioning complex neural networks.
      Our observations employ a custom gradient-index lens probe and voltage-sensitive
      dye fluorescence; the use of epi-illumination rather than dark-field illumination
      provides the dramatic signal-to-noise improvement necessary for fast three
      dimensional imaging.

PMID- 14719665
TI  - Backscattering of beams by forward-peaked scattering media.
AB  - For a beam impinging on a scattering medium the diffusion approximation to the
      radiative transport equation is not valid for analyzing the radiance near the
      source, especially if the medium scatters strongly with a sharp forward peak. To
      analyze the radiance, we use the Fokker-Planck approximation to the radiative
      transport equation. Numerical results show a backscattered ring appearing around
      the beam center. It also appears in Monte Carlo simulations of the radiative
      transport equation. This ring is manifested from successive near-forward
      scattering events, so it requires a directional description. Therefore the
      diffusion approximation cannot predict this ring.

PMID- 14719666
TI  - In vivo flow cytometer for real-time detection and quantification of circulating
      cells.
AB  - An in vivo flow cytometer is developed that allows the real-time detection and
      quantification of circulating fluorescently labeled cells in live animals. A
      signal from a cell population of interest is recorded as the cells pass through a
      slit of light focused across a blood vessel. Confocal detection of the excited
      fluorescence allows continuous monitoring of labeled cells in the upper layers of
      scattering tissue, such as the skin. The device is used to characterize the in
      vivo kinetics of red and white blood cells circulating in the vasculature of the
      mouse ear. Potential applications in biology and medicine are discussed.

PMID- 14719667
TI  - Rapid scanning all-reflective optical delay line for real-time optical coherence
      tomography.
AB  - We describe a dispersion-free high-speed scanning optical delay line that is
      suitable for real-time optical coherence tomography, in particular, when an
      ultrabroadband light source is used. The delay line is based on all-reflective
      optics consisting of two flat and one curved mirrors. We achieve optical path
      length scanning by oscillating one of the two flat mirrors with a resonant
      galvanometer. The delay line is compact and easy to implement. A total scanning
      depth of 1.50 mm with an 89% duty ratio, a maximal scanning speed of
      approximately 9.1 m/s, and a 4.1-kHz repetition rate has been demonstrated.

PMID- 14719668
TI  - Group index of the human cornea at 1.3-microm wavelength obtained in vitro by
      optical coherence domain reflectometry.
AB  - The group index of the cornea, rather than the phase refractive index, is
      required for thickness calculations with optical coherence tomography. Recent
      advances with high-speed optical coherence tomography at 1.3 microm make index
      measurement at this wavelength of great interest. Group indices of three human
      corneas from an eye bank were measured in vitro with optical coherence domain
      reflectometry. Measurements were made in a calibrated cuvette filled with a
      preservation medium to maintain proper corneal hydration. Group indices were
      calculated from the optical path lengths measured. The corneal group index was
      1.389 +/- 0.004 (average +/- standard deviation). The average group index of a
      balanced salt solution, an approximation to aqueous humor, was 1.343 +/- 0.001.

PMID- 14719669
TI  - Enhancement of high-order harmonic generation at tuned wavelengths through
      adaptive control.
AB  - An adaptive learning loop enhances the efficiency and tuning of high-order
      harmonic generation. In comparison with simple chirp tuning, we observe a broader
      tuning range and a twofold to threefold enhancement in integrated photon flux in
      the cutoff region. The driving pulse temporal phase varies significantly for
      different tunings and is more complicated than a simple chirp. We compare our
      experimental results with a one-dimensional, time-dependent model that
      incorporates the intrinsic atomic response, the experimental pulse temporal
      phase, ionization effects, and transverse coherence of the spatial mode of the
      laser. The model agrees with our experimental results and indicates that a
      specific quantum path coupled with ionization effects determines the optimized
      harmonic spectrum.

PMID- 14719670
TI  - Second-harmonic generation in periodically poled nonlinear polymer waveguides.
AB  - We demonstrate quasi-phase-matched (QPM) second-harmonic generation (SHG) at the
      optical communication wavelengths with side-chain polymer waveguides. A ridge
      waveguide structure is designed to support fundamental mode guiding at both the
      pump and the second harmonics, leading to a high field overlap integral of the
      guided modes. The nonlinearity contrast in the +/0 type QPM waveguide is
      maximized under a QPM poling electrode width of nearly half the coherence length.
      Using these configurations, we record a normalized SHG efficiency of 2.2% W(-1)
      cm(-2) in the polymer waveguide.

PMID- 14719671
TI  - Generation of 5-W deep-UV continuous-wave radiation at 266 nm by an external
      cavity with a CsLiB6O10 crystal.
AB  - A Brewster-cut CsLiB6O10 crystal is employed as an external resonant frequency
      doubler to generate cw deep-UV radiation at 266 nm. We have generated 5.0 W of
      usable cw output power, which is 6.1 W in the crystal, for an incident green
      power of 9.6 W, corresponding to an internal conversion efficiency of 61.8%. The
      power obtained is, to our knowledge, three times higher than previously reported
      for cw 266-nm generation.

PMID- 14719672
TI  - Quasi-phase-matched generation of tunable blue light in a quasi-periodic
      structure.
AB  - We present what is to our knowledge a new approach to generating tunable blue
      light by cascaded nonlinear frequency conversion in a single LiTaO3 crystal.
      Simultaneous quasi-phase matching of an optical parametric generation process and
      a sum-frequency mixing process is achieved by means of structuring the crystal
      with a quasi-periodic optical superlattice. The spectral (wavelength tuning and
      bandwidth) and power characteristics of the blue-light generation are studied
      with a fixed-wavelength 532-nm picosecond laser and a wavelength-tunable
      nanosecond optical parametric oscillator (OPO) as the pump sources. By tuning the
      OPO wavelength, we could tune the blue output over approximately 20 nm.
      Temperature tuning of the blue output at a fixed pump wavelength of 532 nm was
      limited to approximately 1.5 nm. A maximum blue power of 15 microW was generated
      at a pump power of 0.5 mW, corresponding to an efficiency of 3%.

PMID- 14719673
TI  - Photoinduction of surface-relief gratings during all-optical poling of polymer
      films.
AB  - Using the all-optical poling method, we observed the formation of a surface
      relief grating (SRG) in an amorphous polymer film containing azo dye molecules in
      side chain positions. The experiment consists of a seeding-type process. We used
      a recently described experimental setup that permits a periodic nonlinear pattern
      to be produced by the index dispersion of glass. The particular configuration
      permits photoinduced translation diffusion of the azo chromophores to be observed
      as the origin of the SRG formation. Analyses of the gratings recorded by use of s
      (TE) and p (TM) polarization of the writing beams are conducted by atomic-force
      microscopy. The effect is attributed to mass transport from regions of high
      isomerization activity to regions of lower activity.

PMID- 14719674
TI  - Holographic simultaneous readout polarization multiplexing based on photoinduced
      anisotropy in bacteriorhodopsin.
AB  - Bacteriorhodopsin (bR) is a reversible photochromic protein that can be used as a
      holographic medium. The dichroic absorption of the bR molecule is polarization
      dependent, thereby allowing for the recording of polarization holograms. The
      properties of polarization holograms can be used to multiplex two independent
      images in a single bR film. A new technique and associated polarization
      multiplexing scheme are demonstrated that allow for simultaneous readout of two
      orthogonally polarized images while achieving a high normalized diffraction
      efficiency for each of the individual images.

PMID- 14719675
TI  - Talbot self-image effect in digital holography and its application to
      spectrometry.
AB  - For the first time to the authors' knowledge, the Talbot effect has been observed
      and investigated in digital holography. By numerical reconstruction of holograms,
      the Talbot self-imaging phenomenon is observed by reconstruction of the amplitude
      of the image at different distances and (or) wavelengths. A simple spectrometer
      based on Talbot self-imaging in digital holography is proposed and demonstrated.

PMID- 14719676
TI  - Filter characteristics of a chirped volume holographic grating.
AB  - We compare and analyze the filter properties of transmission-type volume
      holographic gratings, especially the dispersion characteristics for uniform and
      chirped gratings. It is theoretically and experimentally shown that the
      dispersion characteristics can be controlled by introducing one-dimensional
      chirping to the volume grating in a photorefractive crystal. The filter response
      including output power and dispersion comes from a combined effect of the spatial
      spectra of the grating structure, input beam, and output-coupling fiber mode.
      Filter responses can be designed by controlling these parameters for optical
      communication applications.

PMID- 14719677
TI  - Photorefractive effect induced by polarization gratings in dye-doped liquid
      crystals.
AB  - We report on the photorefractive effect induced by a polarization grating in the
      presence of dc voltage in a dye-doped liquid-crystal (DDLC) film. The writing
      beams are two orthogonally (left- and right-circularly) polarized laser beams
      that create a spatially polarization-modulated interference field with constant
      intensity. The photorefractivity is ascribed to the absorption anisotropy of the
      azo dye. The unique dichroism of a DDLC cell causes a spatial variation in the
      absorption of light in response to a polarization-modulated interference field.
      Such a variation establishes a space-charge field in the presence of dc voltage,
      generating photorefractivity. Two-beam couplings were also verified and measured
      dynamically during the formation of the photorefractive grating in this study.

PMID- 14719678
TI  - Cross talk between holograms of finite contrast in a phase-code multiplexing
      system.
AB  - The cross talk between holograms recorded in a phase-code multiplexing system is
      analyzed. The signal-to-noise ratio (SNR) is derived for the original image of a
      finite contrast ratio in the presence of a phase-shift error of the reference
      beam. It is shown that one particular code in the Walsh-Hadamard code set can be
      the dominant cross-talk noise source. We experimentally measured the SNR of the
      holograms recorded in an 8-bit phase-code multiplexing system by varying the
      contrast ratio of the original image. We show good agreement between experiment
      and theory. The existence of one bad code is also shown experimentally.

PMID- 14719679
TI  - Remote multiplexing of holograms with random patterns from multimode fiber
      bundles.
AB  - We propose the remote multiplexing of holograms with random patterns from a
      multimode fiber bundle used as the reference beams. The random pattern reference
      beam is characterized by the superposition and concatenation of propagation modes
      of multimode fiber and free space. For angle, shift, and wavelength remote
      multiplexing we compare two methods of laser coupling to the fiber bundle, i.e.,
      direct coupling and lens coupling. A theoretical discussion that uses mode
      orthogonality is provided to describe multiplexing characteristics, and the
      theory is verified by experimental results. These remote-multiplexing methods can
      be applied to general multimode waveguide arrays for construction of compact and
      integrated optical systems in which multiplexing can be controlled remotely.

PMID- 14719680
TI  - Form birefringence and negative index change created by femtosecond direct
      writing in transparent materials.
AB  - Although femtosecond lasers have proved to be of great utility for micromachining
      within bulk transparent materials, little is known about the fundamental physics
      that drive the process. Depending on the laser intensity delivered to the sample,
      any of three types of feature can be written into the glass. We observed that in
      the intermediate regime there is a correlation among the negative sign of the
      effective index change, the presence of anisotropic reflection, and
      birefringence. We propose a model that can explain all three principal
      characteristics. Results show that the local index change can be as high as 10(
      1).

PMID- 14719681
TI  - Application of terahertz quantum-cascade lasers to semiconductor cyclotron
      resonance.
AB  - Quantum-cascade lasers operating at 4.7, 3.5, and 2.3 THz have been used to
      achieve cyclotron resonance in InAs and InSb quantum wells from liquid-helium
      temperatures to room temperature. This represents one of the first spectroscopic
      applications of terahertz quantum-cascade lasers. Results show that these compact
      lasers are convenient and reliable sources with adequate power and stability for
      this type of far-infrared magneto-optical study of solids. Their compactness
      promises interesting future applications in solid-state spectroscopy.

PMID- 14719682
TI  - Improving the use of vibro-acoustography for brachytherapy metal seed imaging: a
      feasibility study.
AB  - Vibro-acoustography method is explored for detecting and imaging brachytherapy
      metal seeds in gel phantoms. In a previous paper, we have shown that some
      immersed objects' resonance frequencies could be detected by vibro-acoustography.
      Here, we use this idea to optimize the vibro-acoustic excitation of two different
      sized brass seeds implanted in an agar gel phantom. In the experiments, the best
      excitation vibration frequencies were determined either by calculating
      fundamental resonance frequencies for each of the seeds or the experimental
      optimal resonance frequency of the gel. The resulting vibro-acoustography images
      demonstrate remarkable contrast in acoustic emission amplitude compared with
      images obtained at nonresonance frequencies. Results suggest the possible
      application of vibro-acoustography for directing prostate brachytherapy seed
      implantation treatment.

PMID- 14719683
TI  - Phase unwrapping for 2-D blind deconvolution of ultrasound images.
AB  - In most approaches to the problem of two-dimensional homomorphic deconvolution of
      ultrasound images, the estimation of a corresponding point-spread function (PSF)
      is necessarily the first stage in the process of image restoration. This
      estimation is usually performed in the Fourier domain by either successive or
      simultaneous estimation of the amplitude and phase of the Fourier transform (FT)
      of the PSE This paper addresses the problem of recovering the FT-phase of the
      PSF, which is an important reconstruction problem by itself. The purpose of this
      paper is twofold. First, it provides a theoretical framework, establishing that
      the FT-phase of the PSF can be effectively estimated by a proper smoothing of the
      FT-phase of the appropriate radio-frequency (RF) image. Second, it presents a
      novel approach to the estimation of the FT-phase of the PSF, by solving a
      continuous Poisson equation over a predefined smooth subspace, in contrast to the
      discrete Poisson equation solver used for the classical least mean squares phase
      unwrapping algorithms, followed by a smoothing procedure. The proposed approach
      is possible due to the distinct properties of the FT-phases, among which the most
      important property is the availability of precise values of their partial
      derivatives. This property overcomes the main disadvantage of the discrete
      schemes, which routinely use wrapped (principal) values of the phase in order to
      approximate its partial derivatives. Since such an approximation is feasible
      subject to the restriction that the partial phase differences do not exceed pi in
      absolute value, the discrete schemes perform satisfactory only for few practical
      situations. The proposed approach is shown to be independent of this restriction
      and, thus, it performs for a wider class of the phases with significantly lower
      errors. The main advantages of the novel method over the algorithms based on
      discrete schemes are demonstrated in a series of computer simulations and for in
      vivo measurements.

PMID- 14719684
TI  - Long bone panoramas from fluoroscopic X-ray images.
AB  - This paper presents a new method for creating a single panoramic image of a long
      bone from several individual fluoroscopic X-ray images. Panoramic images are
      useful preoperatively for diagnosis, and intraoperatively for long bone fragment
      alignment, for making anatomical measurements, and for documenting surgical
      outcomes. Our method composes individual overlapping images into an undistorted
      panoramic view that is the equivalent of a single X-ray image with a wide field
      of view. The correlations between the images are established from the graduations
      of a radiolucent ruler imaged alongside the long bone. Unlike existing methods,
      ours uses readily available hardware, requires a simple image acquisition
      protocol with minimal user input, and works with existing fluoroscopic C-arm
      units without modifications. It is robust and accurate, producing panoramas whose
      quality and spatial resolution is comparable to that of the individual images.
      The method has been successfully tested on in vitro and clinical cases.

PMID- 14719685
TI  - Normalized cuts in 3-D for spinal MRI segmentation.
AB  - Segmentation of medical images has become an indispensable process to perform
      quantitative analysis of images of human organs and their functions. Normalized
      Cuts (NCut) is a spectral graph theoretic method that readily admits combinations
      of different features for image segmentation. The computational demand imposed by
      NCut has been successfully alleviated with the Nystrom approximation method for
      applications different than medical imaging. In this paper we discuss the
      application of NCut with the Nystrom approximation method to segment vertebral
      bodies from sagittal T1-weighted magnetic resonance images of the spine. The
      magnetic resonance images were preprocessed by the anisotropic diffusion
      algorithm, and three-dimensional local histograms of brightness was chosen as the
      segmentation feature. Results of the segmentation as well as limitations and
      challenges in this area are presented.

PMID- 14719686
TI  - Automated segmentation of lumbar vertebrae in digital videofluoroscopic images.
AB  - Low back pain is a significant problem in the industrialized world. Diagnosis of
      the underlying causes can be extremely difficult. Since mechanical factors often
      play an important role, it can be helpful to study the motion of the spine.
      Digital videofluoroscopy has been developed for this study and it can provide
      image sequences with many frames, but which often suffer due to noise,
      exacerbated by the very low radiation dosage. Thus, determining vertebra position
      within the image sequence presents a considerable challenge. There have been many
      studies on vertebral image extraction, but problems of repeatability, occlusion
      and out-of-plane motion persist. In this paper, we show how the Hough transform
      (HT) can be used to solve these problems. Here, Fourier descriptors were used to
      describe the vertebral body shape. This description was incorporated within our
      HT algorithm from which we can obtain affine transform parameters, i.e., scale,
      rotation and center position. The method has been applied to images of a
      calibration model and to images from two sequences of moving human lumbar spines.
      The results show promise and potential for object extraction from poor quality
      images and that models of spinal movement can indeed be derived for clinical
      application.

PMID- 14719687
TI  - Measurement of trabecular bone thickness in the limited resolution regime of in
      vivo MRI by fuzzy distance transform.
AB  - Trabecular or cancellous bone, the type of bone found in the vertebrae and near
      the joints of long bones, consists of a network of plates and struts. Accurate
      measurement of trabecular thickness is of significant interest, for example, to
      assess the effectiveness of anabolic (bone forming) agents of patients with
      osteoporosis. Here, we introduce a new fuzzy distance transform (FDT)-based
      thickness computation method that obviates binary segmentation and that can
      effectively deal with images acquired at a voxel size comparable to the typical
      trabecular bone thickness. The method's robustness is shown on the basis of micro
      CT images of human trabecular bone, resampled at progressively coarser resolution
      and after application of rotation and addition of noise as a means to simulate
      the in vivo situation. Reproducibility of the method is demonstrated with micro
      CT images by comparing histograms of thickness within and between data sets and
      with micro-MRI volume data sets of human volunteers imaged repeatedly. Finally,
      with in vivo micro-MR images from a prior study in rabbits subjected to
      corticosteroid exposure, it is demonstrated that short-term treatment resulting
      in trabecular thinning can be quantified with the new method.

PMID- 14719688
TI  - Iso-shaping rigid bodies for estimating their motion from image sequences.
AB  - In many medical imaging applications, due to the limited field of view of imaging
      devices, acquired images often include only a part of a structure. In such
      situations, it is impossible to guarantee that the images will contain exactly
      the same physical extent of the structure at different scans, which leads to
      difficulties in registration and in many other tasks, such as the analysis of the
      morphology, architecture, and kinematics of the structures. To facilitate such
      analysis, we developed a general method, referred to as iso-shaping, that
      generates structures of the same shape from segmented image sequences. The basis
      for this method is to automatically find a set of key points, called shape
      centers, in the segmented partial anatomic structure such that these points are
      present in all images and that they represent the same physical location in the
      object, and then trim the structure using these points as reference. The
      application area considered here is the analysis of the morphology, architecture,
      and kinematics of the joints of the foot from magnetic resonance images acquired
      at different joint positions and load conditions. The accuracy of the method is
      analyzed by utilizing ten data sets for iso-shaping the tibia and the fibula via
      four evaluative experiments. The analysis indicates that iso-shaping produces
      results as predicted by the theoretical framework.

PMID- 14719689
TI  - Low dimensional adaptive texture feature vectors from class distance and class
      difference matrices.
AB  - In many popular texture analysis methods, second or higher order statistics on
      the relation between pixel gray level values are stored in matrices. A high
      dimensional vector of predefined, nonadaptive features is then extracted from
      these matrices. Identifying a few consistently valuable features is important, as
      it improves classification reliability and enhances our understanding of the
      phenomena that we are modeling. Whatever sophisticated selection algorithm we
      use, there is a risk of selecting purely coincidental "good" feature sets,
      especially if we have a large number of features to choose from and the available
      data set is limited. In a unified approach to statistical texture feature
      extraction, we have used class distance and class difference matrices to obtain
      low dimensional adaptive feature vectors for texture classification. We have
      applied this approach to four relevant texture analysis methods. The new adaptive
      features outperformed the classical features when applied to the most difficult
      set of 45 Brodatz texture pairs. Class distance and difference matrices also
      clearly illustrated the difference in texture between cell nucleus images from
      two different prognostic classes of early ovarian cancer. For each of the texture
      analysis methods, one adaptive feature contained most of the discriminatory power
      of the method.

PMID- 14719690
TI  - Clustered components analysis for functional MRI.
AB  - A common method of increasing hemodynamic response (SNR) in functional magnetic
      resonance imaging (fMRI) is to average signal timecourses across voxels. This
      technique is potentially problematic because the hemodynamic response may vary
      across the brain. Such averaging may destroy significant features in the temporal
      evolution of the fMRI response that stem from either differences in vascular
      coupling to neural tissue or actual differences in the neural response between
      two averaged voxels. Two novel techniques are presented in this paper in order to
      aid in an improved SNR estimate of the hemodynamic response while preserving
      statistically significant voxel-wise differences. The first technique is signal
      subspace estimation for periodic stimulus paradigms that involves a simple
      thresholding method. This increases SNR via dimensionality reduction. The second
      technique that we call clustered components analysis is a novel amplitude
      independent clustering method based upon an explicit statistical data model. It
      includes an unsupervised method for estimating the number of clusters. Our
      methods are applied to simulated data for verification and comparison to other
      techniques. A human experiment was also designed to stimulate different
      functional cortices. Our methods separated hemodynamic response signals into
      clusters that tended to be classified according to tissue characteristics.

PMID- 14719692
TI  - Characterization of spiculation on ultrasound lesions.
AB  - Spiculation is a stellate distortion caused by the intrusion of breast cancer
      into surrounding tissue. Its existence is an important clue to characterizing
      malignant tumors. Many successful mammographic methods have been proposed to
      detect tumors with spiculation. Traditional two-dimensional (2-D) ultrasound
      cannot easily find spiculations because spiculations normally appear parallel to
      the surface of the skin. Recently, three-dimensional (3-D) ultrasound has been
      gradually used in clinical applications and it has been proven to be useful in
      determining the architectural distortion or spiculation that surrounds a breast
      tumor. This paper aims to identify spiculation from 3-D ultrasonic volume data of
      a tumor found by a physician. In the proposed method, each coronal slice of
      volume data is successively extracted and then analyzed as a 2-D ultrasound image
      by the proposed spiculation detection method. First, in each horizontal slice,
      the modified rotating structuring element (ROSE) operation is used to find the
      central region in which spiculation lines converge. Second, the stick algorithm
      is used to estimate the direction of the edge of each pixel around the central
      region. A pixel whose edge points toward the central region is marked as a
      potential spiculation. Finally, the marked pixels are collected around the
      central region and their distribution is analyzed to determine whether
      spiculation is present. The 3-D test datasets were obtained using the Voluson 530
      or 730, Kretztechnik, Austria. First, the proposed method was tested on 104 2-D
      typical coronal images (selected by an experienced physician) extracted from 52 3
      D ultrasonic datasets. Finally, 225 3-D pathologically proven datasets were
      tested to evaluate the performance. Spiculations are more easily observed in the
      coronal view than in the other two views. That is, the 3-D ultrasound is a
      powerful tool for identifying spiculations. Furthermore, 16% (19/120) of benign
      cases and 90% (94/105) of malignant cases are detected as spiculations.

PMID- 14719691
TI  - Accurate template-based correction of brain MRI intensity distortion with
      application to dementia and aging.
AB  - This paper examines an alternative approach to separating magnetic resonance
      imaging (MRI) intensity inhomogeneity from underlying tissue-intensity structure
      using a direct template-based paradigm. This permits the explicit spatial
      modeling of subtle intensity variations present in normal anatomy which may
      confound common retrospective correction techniques using criteria derived from a
      global intensity model. A fine-scale entropy driven spatial normalisation
      procedure is employed to map intensity distorted MR images to a tissue reference
      template. This allows a direct estimation of the relative bias field between
      template and subject MR images, from the ratio of their low-pass filtered
      intensity values. A tissue template for an aging individual is constructed and
      used to correct distortion in a set of data acquired as part of a study on
      dementia. A careful validation based on manual segmentation and correction of
      nine datasets with a range of anatomies and distortion levels is carried out.
      This reveals a consistent improvement in the removal of global intensity
      variation in terms of the agreement with a global manual bias estimate, and in
      the reduction in the coefficient of intensity variation in manually delineated
      regions of white matter.

PMID- 14719693
TI  - An analytic method to predict the thermal map of cryosurgery iceballs in MR
      images.
AB  - This paper presents a newly developed method to estimate, in magnetic resonance
      (MR) images, the temperatures reached within the volume of an iceball produced by
      a cryogenic probe. Building on the direct measurements of the MR signal intensity
      and its correlation with independent temperature variations at the phase
      transition from liquid to solid, the thermal information embedded in the images
      was accessed. The volume and diameter of the growing iceball were estimated from
      a time series of MR images. Using regressions over the volume in the time and
      thermal domains, this method predicted the cryogenic temperatures beyond the
      range of sensitivity of the MR signal itself. We present a validation of this
      method in samples of gelatin and ex vivo pig liver. Temperature predictions are
      shown to agree with independent thermosensor readings over a range extending from
      20 degrees C down to -65 degrees C, with an average error of less than 6 degrees
      C.

PMID- 14719694
TI  - Multiscale vessel tracking.
AB  - A method is presented that uses a vectorial multiscale feature image for wave
      front propagation between two or more user defined points to retrieve the central
      axis of tubular objects in digital images. Its implicit scale selection mechanism
      makes the method more robust to overlap and to the presence of adjacent
      structures than conventional techniques that propagate a wave front over a scalar
      image representing the maximum of a range of filters. The method is shown to
      retain its potential to cope with severe stenoses or imaging artifacts and
      objects with varying widths in simulated and actual two-dimensional angiographic
      images.

PMID- 14719695
TI  - Association between soil type and paratuberculosis in cattle herds.
AB  - OBJECTIVE: To determine the association between soil type and paratuberculosis in
      cattle. SAMPLE POPULATION: Soil samples and test results for paratuberculosis in
      92 Indiana cattle herds. PROCEDURE: Testing records from herds in which > or = 20
      cattle were tested for paratuberculosis by use of an ELISA between 1998 and 2002
      were identified. Soil type was characterized on the basis of herd location.
      Clusters of herds with seroprevalence greater than the median seroprevalence were
      identified. Association between clusters and soil types was estimated by logistic
      regression, adjusted for herd type (dairy or beef). RESULTS: A spatial cluster of
      greater than the median seroprevalence was identified in northeast Indiana. Soils
      with low silt content were associated (odds ratio [OR], 7.2; 95% confidence
      interval [CI], 2.1 to 24.5) with this cluster. Adjusting for herd type did not
      substantially alter this association (OR, 6.7). Herds located in areas with sandy
      loam (OR, 6.2; 95% CI, 1.4 to 27.4) and loam (OR, 3.6; 95% CI, 1.0 to 13.2) soils
      were also more likely to be within the cluster of greater than the median
      seroprevalence. Herds located in areas of silt loam soils were less likely (OR,
      0.2; 95% CI, 0.1 to 0.7) to be included in this cluster. CONCLUSIONS AND CLINICAL
      RELEVANCE: Spatial distribution of herds with greater than the median
      seroprevalence of paratuberculosis was associated with soil characteristics.
      Survival of Mycobacterium avium subsp paratuberculosis may be enhanced by silt or
      sand content in loamy soils. These results may be used to modify paratuberculosis
      control programs.

PMID- 14719696
TI  - Nucleotide sequence of equine erythropoietin and characterization of region
      specific antibodies.
AB  - OBJECTIVE: To determine the full-length complementary DNA (cDNA) sequence of
      equine erythropoietin (EPO) and to develop region-specific antibodies to
      differentiate equine EPO (eEPO) and human EPO (hEPO). SAMPLE POPULATION: RNA and
      lysate extracted from renal tissues of an adult Thoroughbred. PROCEDURE: Full
      length cDNA was determined by use of a reverse transcriptase-polymerase chain
      reaction assay and a rapid amplification of cDNA ends method. The deduced amino
      acid sequence was compared with sequences of EPO reported for other species.
      Furthermore, 4 synthetic peptides were designed in 2 distinctive parts of the
      eEPO and hEPO amino acid sequences to obtain antibodies specific for eEPO and
      hEPO. Specificity of the antibodies was tested against supernatant of homogenized
      equine kidney and recombinant hEPO (rhEPO) by use of western immunoblotting
      techniques. RESULTS: Analysis of the 1,181 bp in the nucleotide sequence revealed
      that eEPO was a residue of 192 amino acids. Similarity of eEPO with amino acid
      sequences of EPO from other species was 81.0% to 90.6%. Antibodies were
      specifically recognized by eEPO or rhEPO molecules. Anti-hEPO (161 to 165)
      antibody specifically recognized rhEPO. In contrast, anti-eEPO (133 to 144)
      antibody reacted with the equine kidney lysate. CONCLUSIONS AND CLINICAL
      RELEVANCE: We determined the cDNA and amino acid sequence of eEPO and developed
      region-specific antibodies that specifically recognized eEPO or rhEPO. These
      antibodies may be useful in distinguishing rhEPO from eEPO in a test to detect
      the misuse of rhEPO in racehorses.

PMID- 14719697
TI  - Hemodynamic effects of sevoflurane in cats.
AB  - OBJECTIVE: To determine hemodynamic effects of 3 concentrations of sevoflurane in
      cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with sevoflurane in
      oxygen. After instruments were inserted, end-tidal sevoflurane concentration was
      set at 1.25, 1.5, or 1.75 times the individual minimum alveolar concentration
      (MAC), which was determined in another study. Twenty-five minutes were allowed
      after each change of concentration. Heart rate; systemic and pulmonary arterial
      pressures; central venous pressure; pulmonary artery occlusion pressure; cardiac
      output; body temperature; arterial and mixed-venous pH, PCO2, PO2, oxygen
      saturation, and hemoglobin concentrations; PCV; and total protein and lactate
      concentrations were measured for each sevoflurane concentration before and during
      noxious stimulation. Arterial and mixed-venous bicarbonate concentrations,
      cardiac index, stroke index, rate-pressure product, systemic and pulmonary
      vascular resistance indices, left and right ventricular stroke work indices,
      PaO2, mixed-venous partial pressure of oxygen (PVO2), oxygen delivery, oxygen
      consumption, oxygen-extraction ratio, alveolar-to-arterial oxygen difference, and
      venous admixture were calculated. Spontaneous and mechanical ventilations were
      studied during separate experiments. RESULTS: Mode of ventilation did not
      significantly influence any of the variables examined. Therefore, data from both
      ventilation modes were pooled for analysis. Mean arterial pressure, cardiac
      index, stroke index, rate-pressure product, left ventricular stroke work index,
      arterial and mixed-venous pH, PaO2, and oxygen delivery decreased, whereas PaCO2,
      PVO2, and mixed-venous partial pressure of CO2 increased significantly with
      increasing doses of sevoflurane. Noxious stimulation caused a significant
      increase in most cardiovascular variables. CONCLUSIONS AND CLINICAL RELEVANCE:
      Sevoflurane induces dose-dependent cardiovascular depression in cats that is
      mainly attributable to myocardial depression.

PMID- 14719698
TI  - Effects of injection of botulinum toxin type B into the external anal sphincter
      on anal pressure of horses.
AB  - OBJECTIVE: To determine effects on anal pressure of horses after local injection
      of the external anal sphincter with Clostridium botulinum toxin type B. ANIMALS:
      11 healthy adult horses. PROCEDURE: Peak and resting anal sphincter pressures
      were measured with a custom-made rectal probe that was connected to a pressure
      transducer. Pressures were measured before treatment and after injection with
      botulinum toxin type B (BTB) or saline (0.9% NaCl) solution. Dose titration with
      500, 1,000, 1,500, and 2,500 U of BTB was completed. Physical changes, behavior,
      and anal pressure were recorded for each horse. RESULTS: Injection of 1,000 U of
      BTB caused a significant reduction in peak anal pressure from days 2 to 84,
      compared with pressure in control horses. Maximal effect of the toxin was
      observed within the first 15 days after injection, followed by a slow return to
      baseline during the 168-day period. Injection of 2,500 U of BTB in the anal
      sphincter in 1 horse resulted in lethargy, generalized weakness, and dysphagia
      for 14 days. Adverse clinical effects were not observed in horses after
      injections with 500, 1,000, or 1,500 U of BTB. CONCLUSIONS AND CLINICAL
      RELEVANCE: The effect of focal intramuscular injection of BTB in horses is
      similar to that reported for other species. However, horses appear to be more
      sensitive to BTB, compared with other species, and clinical signs of botulism may
      develop at doses exceeding 1,500 U. Injections of BTB in the external anal
      sphincter of mares may be useful to reduce incisional dehiscence after repair of
      perineal lacerations.

PMID- 14719699
TI  - Evaluation of urine sucrose concentration for detection of gastric ulcers in
      horses.
AB  - OBJECTIVE: To evaluate the use of sucrose permeability testing to detect ulcers
      in the gastric squamous mucosa of horses. ANIMALS: 13 adult horses ranging from 5
      to 19 years of age. PROCEDURE: Following induction of gastric ulcers by
      intermittent feed deprivation, horses underwent sucrose permeability testing
      (administration of sucrose by nasogastric intubation followed by collection of
      urine at 2 and 4 hours after intubation) and gastric endoscopy. Squamous ulcers
      were assigned a severity score (range, 0 to 3) by use of an established scoring
      system. Horses were subsequently administered omeprazole for 21 days, and sucrose
      testing and endoscopy were repeated. Pair-wise comparisons of urine sucrose
      concentration were made between horses with induced ulcers before and after
      omeprazole treatment. Urine sucrose concentrations also were compared on the
      basis of ulcer severity score. RESULTS: Urine sucrose concentrations and ulcer
      severity scores were significantly higher in horses with induced ulcers before
      omeprazole treatment than after treatment. Urine sucrose concentrations were
      significantly higher for horses with ulcer severity scores > 1. Use of a cut
      point value of 0.7 mg/mL revealed that the apparent sensitivity and specificity
      of sucrose permeability testing to detect ulcers with severity scores > 1 was 83%
      and 90%, respectively. Results were similar after adjusting sucrose
      concentrations for urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Urine
      sucrose concentration appears to be a reliable but imperfect indicator of gastric
      squamous ulcers in horses. Sucrose permeability testing may provide a simple,
      noninvasive test to detect and monitor gastric ulcers in horses.

PMID- 14719700
TI  - Diversity of Salmonella serovars in feedyard and nonfeedyard playas of the
      Southern High Plains in the summer and winter.
AB  - OBJECTIVE: To compare Salmonella isolates cultured from feedyard and nonfeedyard
      (control) playas (ie, temporary shallow lakes) of the Southern High Plains.
      SAMPLE POPULATION: Water and muck (sediment) samples were obtained from 7
      feedyard playas and 3 nonfeedyard playas in the winter and summer. PROCEDURE:
      Each water and muck sample was enriched with sulfur-brilliant-green broth and
      incubated in a shaker at 37 degrees C for 24 hours. A sample (100 mL) of the
      incubated bacterial-enriched broth was then mixed with 100 mL of fresh sulfur
      brilliant-green enrichment broth and incubated in a shaker at 37 degrees C for 24
      hours. After the second incubation, a swab sample was streaked on differential
      media. Suspect Salmonella isolates were further identified by use of biochemical
      tests, and Salmonella isolates were confirmed and serovar determinations made.
      RESULTS: Salmonella isolates were not recovered from the 3 control playas. Seven
      Salmonella enterica serovars were isolated from 5 of 7 feedyard playas in the
      summer, and 13 S. enterica serovars were isolated from 7 of 7 feedyard playas in
      the winter. In the summer, 296 isolates were cultured, and 47 were Salmonella
      organisms. In the winter, 288 isolates were cultured, and 171 were Salmonella
      organisms. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that feedyard
      playas are frequently contaminated with many Salmonella serovars. These pathogens
      should be considered whenever feedyard managers contemplate the use of water from
      these playas. Water from feedyard playas should not be used to cool cattle in the
      summer or for dust abatement.

PMID- 14719701
TI  - Comparison of the type and number of microorganisms and concentration of
      endotoxin in the air of feedyards in the Southern High Plains.
AB  - OBJECTIVES: To determine the bacterial, fungal, and endotoxin concentrations in
      aerosolized ambient air during the winter and summer in feedyards located in the
      Southern High Plains, identify aerosolized microbial pathogens, and determine the
      size of microbial and dust components. SAMPLE POPULATION: Aerosol samples were
      obtained from 7 feedyards. PROCEDURE: Aerosol samples were collected upwind, on
      site, and downwind from each feedyard at a point 1 m above the ground by use of
      biological 2- and 6-stage cascade impactors. RESULTS: Significantly more microbes
      were cultured from on-site and downwind samples than upwind samples. There were
      significantly more microbes during the summer than during the winter. However,
      mean endotoxin concentration was significantly higher during the winter (8.37
      ng/m3) than the summer (2.63 ng/m3). Among 7 feedyards, mean +/- SE number of
      mesophilic bacteria (1,441 +/- 195 colony-forming units [CFUs]/m3) was
      significantly higher than mean number of anaerobic bacteria (751 +/- 133 CFUs/m3)
      or thermophilic bacteria (54 +/- 10 CFUs/m3) in feedyard air. Feedyard aerosol
      samples contained more mesophilic fungi (78 +/- 7 CFUs/m3) than thermophilic
      fungi (2 +/- 0.2 CFUs/m3). Eighteen genera of bacteria were identified by use of
      an automated identification system. CONCLUSIONS AND CLINICAL RELEVANCE: It
      appeared that gram-negative enteric pathogens offered little risk to remote
      calves or humans via ambient aerosols and that gram-positive pathogens of the
      Bacillus, Corynebacterium, and Staphylococcus spp can be spread by aerosols in
      and around feedyards. It was common to detect concentrations of endotoxin in the
      ambient air of 7 feedyards.

PMID- 14719702
TI  - Cloning and sequencing of the canine and feline cardiac troponin I genes.
AB  - OBJECTIVE: To determine the gene sequences of canine and feline cardiac troponin
      I (cTnI), express the protein from the cloned gene in vitro, and validate the use
      of a commercial cTnI serum analyzer in these species via detection of the
      expressed protein or comparison of sequence homology. SAMPLE POPULATION: Samples
      of ventricular myocardium from 5 healthy adult mixed-breed dogs and 5 healthy
      adult domestic shorthair cats. PROCEDURE: The RNA was extracted from myocardial
      samples, and cDNA was synthesized via reverse transcriptase polymerase chain
      reaction and sequenced. The canine cDNA for the coding region was expressed in
      cell culture and analyzed by western blot and sandwich enzyme-linked
      immunosorbent assays. RESULTS: Canine and feline cTnI genes were cloned and
      sequenced. Homology of the nucleotide and amino acid sequences of the canine and
      feline cTnI genes with human and rodent cTnI genes were high; the greatest
      homology was detected between canine and feline genes (95% and 96%,
      respectively). Recombinant canine cTnI protein was detected by a commercial serum
      cTnI analyzer and by western blot analysis. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that commercial cTnI analyzers can be used to measure serum
      cTnI concentration from dogs and cats. Additionally, our preliminary
      characterization of the feline cTnI gene may facilitate further investigation of
      cTnI and its role in familial hypertrophic cardiomyopathy in cats.

PMID- 14719703
TI  - Evaluation of leukocyte cell surface markers in dogs with septic and nonseptic
      inflammatory diseases.
AB  - OBJECTIVE: To determine whether functional alterations in neutrophils and
      mononuclear leukocytes are a consistent finding in dogs with inflammatory
      disease. ANIMALS: 40 healthy dogs, 30 dogs with nonseptic inflammatory diseases,
      25 dogs with septic inflammation, and 8 dogs with multiple organ dysfunction
      syndrome (MODS) secondary to sepsis. PROCEDURES: Neutrophil size and granularity;
      expression of cell surface molecules including CD18, CD11b, and mature neutrophil
      antigen on neutrophils; and major histocompatability antigen class II (MHC class
      II) expression on monocytes and lymphocytes were evaluated by use of flow
      cytometry. Neutrophil size and granularity were evaluated by use of forward-angle
      versus side-angle light scatterplots. Leukocytes were labeled with monoclonal
      antibodies to quantify surface expression of leukocyte antigens. RESULTS: Dogs
      with septic and nonseptic inflammatory diseases and MODS had an increase in
      percentage of neutrophils with increased size; dogs with septic inflammation and
      MODS had a greater percentage of neutrophils with decreased granularity. Dogs
      with septic and nonseptic inflammation and MODS had a low expression of CD18 and
      mature neutrophil antigen. Dogs with septic and nonseptic inflammation had an
      increase in CD11b expression. Monocytes from dogs with septic and nonseptic
      inflammation and MODS had a low expression of CD18. Monocytes and lymphocytes
      from dogs with septic and nonseptic inflammation and MODS had a low expression of
      MHC class II. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils from dogs with
      septic and nonseptic inflammation circulate in an activated state, and some dogs
      have decreased MHC class II expression. Many dogs with MODS have a compensatory
      anti-inflammatory response that may compromise their responses to antimicrobials.

PMID- 14719704
TI  - Effects of two anti-inflammatory drugs on physiologic variables and milk
      production in cows with endotoxin-induced mastitis.
AB  - OBJECTIVE: To determine the effects of 2 anti-inflammatory drugs in lactating
      Holstein cows with endotoxin-induced mastitis. ANIMALS: 30 multiparous Holstein
      cows that had been lactating for 30 to 60 days. PROCEDURE: Bacterial culture of
      milk samples and physical examinations established that study cows were in good
      health and free of mastitis. Mastitis was induced in 1 front mammary gland by
      intramammary administration of purified bacterial endotoxin. Cows were allocated
      into 1 of 3 treatment groups: untreated endotoxic mastitis (n = 9), endotoxic
      mastitis plus flunixin meglumine (9), and endotoxic mastitis plus isoflupredone
      acetate (10). Heart rate, rectal temperature, mammary surface area, and rumen
      motility were recorded hourly for 14 hours following endotoxin administration.
      Flunixin meglumine or isoflupredone acetate was administered after mammary
      swelling and rectal temperature > or = 40 degrees C had developed. Milk
      production was evaluated from 5 days before to 10 days after induction of
      mastitis. RESULTS: Neither drug ameliorated loss of milk production or swelling
      of the affected mammary gland. Both drugs reduced mean heart rate during the 14
      hours following endotoxin administration, compared with untreated control cows.
      Cows treated with flunixin meglumine had increased rumen motility and decreased
      rectal temperature during the same period, compared with all other cows.
      CONCLUSIONS AND CLINICAL RELEVANCE: Neither drug enhanced recovery of milk
      production following endotoxin-induced mastitis. Flunixin meglumine decreased
      rectal temperature, whereas isoflupredone did not; however, it has not been
      established that reduction of fever is beneficial to cows with naturally
      occurring mastitis.

PMID- 14719705
TI  - Immunohistochemical identification and fiber type specific localization of
      protein kinase C isoforms in equine skeletal muscle.
AB  - OBJECTIVE: To investigate whether protein kinase C (PKC) isoforms are expressed
      in equine skeletal muscle and determine their distribution in various types of
      fibers by use of immunofluorescence microscopy. ANIMALS: 5 healthy adult Dutch
      Warmblood horses. PROCEDURE: In each horse, 2 biopsy specimens were obtained from
      the vastus lateralis muscle. Cryosections of equine muscle were stained with PKC
      isoform (alpha, beta1, beta2, delta, epsilon, or zeta)-specific polyclonal
      antibodies and examined by use of a fluorescence microscope. Homogenized muscle
      samples were evaluated via western blot analysis. RESULTS: The PKC alpha, beta1,
      beta2, delta, epsilon, and zeta isoforms were localized within the fibers of
      equine skeletal muscle. In addition, PKC alpha and beta2 were detected near or in
      the plasma membrane of muscle cells. For some PKC isoforms, distribution was
      specific for fiber type. Staining of cell membranes for PKC alpha was observed
      predominantly in fibers that reacted positively with myosin heavy chain (MHC)
      IIa; PKC delta and epsilon staining were more pronounced in MHC-I-positive
      fibers. In contrast, MHC-I negative fibers contained more PKC zeta than MHC-I
      positive fibers. Distribution of PKC beta1 was equal among the different fiber
      types. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that PKC isoforms
      are expressed in equine skeletal muscle in a fiber type-specific manner.
      Therefore, the involvement of PKC isoforms in signal transduction in equine
      skeletal muscle might be dependent on fiber type.

PMID- 14719706
TI  - Effect of oral administration of dantrolene sodium on serum creatine kinase
      activity after exercise in horses with recurrent exertional rhabdomyolysis.
AB  - OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on
      serum creatine kinase (CK) activity after exercise in horses with recurrent
      exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds
      with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg,
      p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing,
      plasma dantrolene concentration was measured spectrofluorometrically. On the
      basis of these results, 5 Thoroughbreds with RER from which food was withheld
      received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90
      minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods.
      Serum CK activity was determined 4 hours after exercise. Plasma dantrolene
      concentration was measured before and 90 minutes after dosing on the first and
      last days of dantrolene treatment and before dosing on the first day of the inert
      treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma
      dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and
      inert treatment groups, respectively. Serum CK activity was lower in dantrolene
      treated horses (264 +/- 13 U/L), compared with activity in water-treated horses
      (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert
      treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which
      food had been withheld, 4 mg of dantrolene/kg administered orally provided
      measurable, though variable, plasma concentrations and significantly decreased
      serum CK activity after exercise in 4 of those horses.

PMID- 14719707
TI  - Pulmonary epithelial lining fluid and plasma ascorbic acid concentrations in
      horses affected by recurrent airway obstruction.
AB  - OBJECTIVE: To determine the pulmonary epithelial lining fluid (ELF)
      concentrations and degree of oxidation of ascorbic acid in horses affected by
      recurrent airway obstruction (RAO) in the presence and absence of neutrophilic
      airway inflammation. ANIMALS: 6 RAO-affected horses and 8 healthy control horses.
      PROCEDURE: Nonenzymatic antioxidant concentrations were determined in RBC,
      plasma, and ELF samples of control horses and RAO-affected horses in the presence
      and absence of airway inflammation. RESULTS: ELF ascorbic acid concentration was
      decreased in RAO-affected horses with airway inflammation (median, 0.06 mmol/L;
      25th and 75th percentiles, 0.0 and 0.4 mmol/L), compared with RAO-affected horses
      without airway inflammation (1.0 mmol/L; 0.7 and 1.5 mmol/L) and control horses
      (2.2 mmol/L; 1.4 and 2.2 mmol/L). Epithelial lining fluid ascorbic acid remained
      significantly lower in RAO-affected horses without airway inflammation than in
      control horses. Moreover, the ELF ascorbic acid redox ratio (ie, ratio of the
      concentrations of dehydroascorbate to total ascorbic acid) was higher in RAO
      affected horses with airway inflammation (median, 0.85; 25th and 75th
      percentiles, 0.25 and 1.00), compared with RAO-affected horses without airway
      inflammation (0.04; 0.02 and 0.22). The number of neutrophils in bronchoalveolar
      lavage fluid was inversely related to the ELF ascorbic acid concentration (r = 
      0.81) and positively correlated with the ascorbic acid redox ratio (r = 0.65).
      CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophilic inflammation in horses affected
      by RAO is associated with a reduction in the ELF ascorbic acid pool. Nutritional
      supplementation with ascorbic acid derivatives in horses affected by RAO is an
      area for further investigation.

PMID- 14719708
TI  - Use of a polymerase chain reaction assay and an ELISA to monitor porcine
      circovirus type 2 infection in pigs from farms with and without postweaning
      multisystemic wasting syndrome.
AB  - OBJECTIVE: To determine whether correlations exist between viremia with porcine
      circovirus type 2 (PCV2) and serum antibody profiles and between detection of
      PCV2 in nasal cavities and viremia of pigs from farms with and without
      postweaning multisystemic wasting syndrome (PMWS). ANIMALS: 495 pigs, ranging
      from the late nursery stage to the early grower-finisher stage of production.
      PROCEDURE: Serum antibodies to PCV2 were studied with an ELISA that detects the
      ORF2 viral protein. Nasal swab specimens and serum samples were tested with a
      PCV2-specific PCR assay. RESULTS: PCV2 DNA and serum antibodies to PCV2 were
      detected in pigs from all farms, although in different proportions. Overall, PCV2
      DNA was detected in greater percentages in serum samples and nasal swab specimens
      of pigs from farms with PMWS. Although viral DNA was detected in both serum
      samples and nasal swab specimens, PCV2 detection in nasal swab specimens was
      higher than in serum samples of pigs from all farms. Serum antibodies to PCV2
      were detected in a greater percentage of pigs from farms with PMWS, compared with
      farms without PMWS. CONCLUSIONS AND CLINICAL RELEVANCE: A high prevalence of PCV2
      infection was found in pigs from farms with and without PMWS. Besides the
      presence of PCV2, unknown additional factors may be necessary to induce the full
      expression of PMWS.

PMID- 14719709
TI  - Relationship of bispectral index to minimum alveolar concentration multiples of
      sevoflurane in cats.
AB  - OBJECTIVE: To determine the relationship between bispectral index (BIS) and
      minimum alveolar concentration (MAC) multiples of sevoflurane in cats. ANIMALS: 8
      domestic cats. PROCEDURE: Each cat was anesthetized twice with sevoflurane.
      First, the MAC of sevoflurane for each cat was determined by use of the tail
      clamp method. Second, cats were anesthetized with sevoflurane at each of 5 MAC
      multiples administered in random order. Ventilation was controlled, and after a
      15-minute equilibration period at each MAC multiple of sevoflurane, BIS data were
      collected for 5 minutes and the median value of BIS calculated. RESULTS: The mean
      (+/- SD) MAC of sevoflurane was 3.3 +/- 0.2%. The BIS values at 0.5 MAC could not
      be recorded as a result of spontaneous movement in all 8 cats. The BIS values at
      2.0 MAC were confounded by burst suppression in all 8 cats. Over the range of 0.8
      to 1.5 MAC, BIS values decreased significantly with increasing end-tidal
      sevoflurane concentrations. Mean (+/- SD) BIS measurements were 30 +/- 3, 21 +/-
      3, and 5 +/- 2 at 0.8, 1.0, and 1.5 MAC, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: Values of BIS are inversely and linearly related to end-tidal
      sevoflurane concentrations in anesthetized cats, and BIS may be a useful
      predictor of CNS depression in this species. The consistently low BIS values
      recorded in this study suggest that clinical BIS end points used to titrate
      anesthetic agents in humans may not be applicable to cats.

PMID- 14719710
TI  - Development of a polymerase chain reaction-based method to identify species
      specific components in dog food.
AB  - OBJECTIVES: To determine whether there is a relationship between species-specific
      mitochondrial DNA (mtDNA), especially canine and feline mtDNA, and detectable
      amounts of pentobarbital in previously analyzed dog food samples. SAMPLE
      POPULATION: 31 dog food samples previously analyzed for pentobarbital (limit of
      detection, 1 microg/kg). PROCEDURE: Polymerase chain reaction (PCR) analysis was
      performed on dog food samples by use of PCR primers specific for either canine,
      feline, equine, bovine, porcine, ovine, or poultry mtDNA. RESULTS: PCR amplicons
      specific for feline or canine mtDNA at a 0.007% (70 microg/g [wt/wt basis]) or
      0.0007% (7 microg/g) level, respectively, were not found in the 31 dog food
      samples. Most of the 31 dog food samples had a PCR amplicon on PCR analysis when
      a PCR primer set capable of simultaneously detecting mtDNA of cows, pigs, sheep,
      goats, deer, elk, and horses was used. Results of PCR analysis by use of primers
      specific for bovine, swine, sheep and goat, or horse mtDNA revealed amplicons
      specific for bovine or swine mtDNA only in 27 of the 31 samples. Analysis of the
      remaining 4 samples failed to yield amplicons for any mammalian mtDNA.
      Pentobarbital was detected in 2 of these 4 samples. Results of PCR analysis
      correlated with the stated ingredient list for most, but not all samples.
      CONCLUSIONS AND CLINICAL RELEVANCE: Because canine and feline mtDNA were not
      found in a set of retail dog food samples, these results indicate that the source
      of pentobarbital in dog food is something other than proteins from rendered pet
      remains.

PMID- 14719711
TI  - Evaluation of plasma carboxy-terminal cross-linking telopeptide of type I
      collagen concentration in horses.
AB  - OBJECTIVE: To evaluate a human assay for quantification of carboxy-terminal cross
      linking telopeptide of type I collagen (CTX-I), assess the influence of age on
      plasma CTX-I concentration, investigate the relationship between plasma CTX-I and
      serum osteocalcin concentrations, and determine whether concentrations of plasma
      CTX-I or serum osteocalcin fluctuate in circadian manner in horses. HORSES: 75
      clinically normal horses. PROCEDURE: Cross-reactivity between equine serum CTX-I
      and CTX-I antibodies in an automated electrochemiluminescent sandwich antibody
      assay (ECLIA) was evaluated via a specificity test (ie, dilution test) and
      recovery calculation. Serum osteocalcin concentration was measured with an equine
      specific osteocalcin radioimmunoassay. To analyze diurnal variations in plasma
      CTX-I and serum osteocalcin concentrations, blood samples were obtained hourly
      during a 24-hour period. RESULTS: Results of the dilution test indicated good
      correlation (r > 0.99) between expected serum CTX-I concentrations and measured
      serum CTX-I concentrations. The calculated CTX-I recovery was 97.6% to 109.9%.
      Plasma CTX-I and serum osteocalcin concentrations were correlated. Plasma CTX-I
      concentration was inversely correlated with age of the horse. No significant
      circadian variations in plasma CTX-I and serum osteocalcin concentrations were
      detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the fully
      automated CTX-I ECLIA can be used for evaluation of plasma and serum samples from
      horses and may be a useful tool to monitor bone metabolism changes. Horses in
      this study did not have notable diurnal fluctuations in serum osteocalcin and
      plasma CTX-I concentrations.

PMID- 14719712
TI  - Expression of bone morphogenetic protein-6 and -2 and a bone morphogenetic
      protein antagonist in horses with naturally acquired osteochondrosis.
AB  - OBJECTIVE: To determine the mRNA expression of bone morphogenetic protein (BMP)-6
      and -2 and a BMP antagonist (Noggin) in horses with osteochondrosis. SAMPLE
      POPULATION: Samples of articular cartilage from affected stifle or shoulder
      joints of 10 immature horses with naturally acquired osteochondrosis and
      corresponding joints of 9 clinically normal horses of similar age; additionally,
      samples of distal femoral growth plate cartilage and distal femoral articular
      cartilage were obtained from a normal equine fetus. PROCEDURE: Cartilage
      specimens were snap-frozen in liquid nitrogen, and total RNA was isolated.
      Adjacent specimens were fixed in 4% paraformaldehyde for histologic examination.
      Expression of BMP-6, BMP-2, and Noggin mRNA was evaluated by real-time
      quantitative polymerase chain reaction (PCR) assays. Spatial tissue mRNA
      expression of BMP-6 was determined by in situ hybridization. RESULTS: Nucleotide
      sequences were obtained for portions of the BMP-6 propeptide and mature peptide
      region, as well as the signal and mature peptide region of Noggin. Expression of
      BMP-6, BMP-2, and Noggin mRNA was found to be similar in cartilage from normal
      and osteochondrosis-affected horses. Spatial expression of BMP-6 correlated with
      the middle and deep layers of articular cartilage; no differences were observed
      in overall expression between cartilage specimens from the 2 groups of horses. No
      expression of BMP-6 was found in the superficial layer, subchondral bone, or
      osteochondrosis-affected cleft fibrous tissue. CONCLUSIONS AND CLINICAL
      RELEVANCE: Although these signaling peptides may play important roles in
      cartilage differentiation, results did not provide evidence to suggest that they
      are involved in the disease process of osteochondrosis.

PMID- 14719714
TI  - Opioid effectiveness and side effects in chronic pain.
AB  - Opioids can provide effective analgesia by way of different routes of
      administration without limiting side effects for most patients suffering from
      chronic pain when clinicians properly manage the pertinent patient-, pain-, and
      drug-centered characteristics. Randomized, placebo-controlled, prospective
      studies are needed to establish a causal relationship between opioids and
      hypogonadism. Many of the current studies are retrospective, which only lead to
      suggestive associations between opioids and hypogonadism and incorporate bias.
      Clinicians may incorporate available tools, including urine toxicology tests, to
      assess any aberrant behavior on the part of patients using opioids and to
      maximize compliance with an opioid regimen.

PMID- 14719715
TI  - Botulinum toxin therapy in pain management.
AB  - BTs seem to be a useful treatment in refractory MPS and headache. Presumably BTs
      work by breaking the spasm or pain cycle giving the patient a "window of
      opportunity" for traditional conservative measures to have a greater beneficial
      impact, but several studies suggest that a direct antinociceptive effect distinct
      from any reduction in muscle spasm may be at play. The major benefit of BTs
      compared with standard therapies is duration of response. We do not advocate that
      BTs be used as a first line treatment for MPS or headache. However, in refractory
      cases where nothing else has worked, it may offer a chance for improvement or
      cure not otherwise available. For now, it remains an off label, but increasingly
      accepted, approach in-patients with refractory myofascial pain and headache, who
      despite multidisciplinary approaches, continue to suffer.

PMID- 14719716
TI  - Complex regional pain syndrome.
AB  - As suggested by this article, considerable advances in clinical management and
      research have taken place during the past 20 years. Although mechanisms
      underlying the pain syndrome CRPS I and CRPS II remain far from one's
      understanding, glimpses of the pathophysiology are beginning to take shape. There
      is now strong evidence that these syndromes exemplify a complex neurologic
      disease involving the brain at several integrated levels. The changes that occur
      in CRPS I patients involve somatosensory, sympathetic, and somatomotor systems.
      The diagnostic criteria have helped to focus on aspects of these foregoing
      systems and whereas there is no specific laboratory test for CRPS, enough is now
      known about the pathophysiology to use the following tests: quantitative sensory
      testing (QST), autonomic testing that include quantitative sudomotor axon reflex
      test (QSART) for sweating abnormalities, the cold pressor test in conjunction
      with thermographic imaging to observe the vasoconstrictor response, and laser
      Doppler flowmetry to monitor background vasomotor control. Recognition of a motor
      disorder requires accurate documentation and may be a component of the diagnostic
      criteria in the future. Until a better understanding of mechanistic overtones
      that would help to put in place mechanism-based therapeutic strategies, current
      management is built around a rehabilitation model. For this to be successful, as
      described in the foregoing pages, different non-interventional and interventional
      modalities are applied in a time-restricted manner to facilitate those modalities
      that favor progress in the treatment algorithm. As has been described, it is
      important when using physiotherapeutic maneuvers to minimize joint movement in
      the affected region to reduce the mechanorecpetor barrage and its increase in
      perceived pain to encourage and maintain a patient's compliance with their
      rehabilitation. Finally, of greater significance is the understanding that
      sympatholysis per se is not a "diagnostic" test for CRPS, but rather a useful
      procedure that may facilitate treatment for pain that is sympathetically
      maintained.

PMID- 14719717
TI  - Special techniques in pain management: lysis of adhesions.
AB  - Low back pain, with or without radicular symptoms, is a common medical condition.
      It can cause mild to severe suffering, high health costs, and disability. Most
      sufferers recover quickly and are left without sequelae. The less fortunate group
      of patients who do not improve despite conservative and mildly interventional
      therapy, find themselves in search of a more effective treatment. To enhance
      treatment outcome, an understanding of the pathophysiology of the underlying pain
      and the design of target-specific treatment modalities is important.

PMID- 14719718
TI  - Psychological aspects of interventional therapy.
AB  - This discussion is not, nor could it hope to be, an exhaustive examination of all
      of the various interventional therapies. Instead, it is intended to highlight the
      potential contribution of psychosocial factors. These factors may vary to some
      degree or another depending on the specific procedure, but clearly play a role
      whenever the desired outcome involves a reduction in subjective pain, alteration
      in the adaptiveness with which the patient responds to the experience of pain,
      and quality of life. Many notables, including Dr. Michael Cousins, have echoed
      the importance of incorporating interventional therapies into an
      interdisciplinary approach. Yet, there seems to be a preponderance of "block
      shops". Even when used for diagnostic or prognostic purposes, the impact of
      psychosocial variables and the potential relevance of a meaningful behavioral or
      psychologic evaluation cannot be overstated. It is easy to understand how the
      reader might conclude that immersing oneself in the minutiae of all these
      variables could lead to a feeling of intellectual paralysis when it comes to
      evaluating the data and arriving at a conclusion or diagnosis. However, ignoring
      these psychosocial variables and their complex interaction does not constitute a
      solution. This is particularly true in considering discography where, depending
      on the criteria applied, the percent of "false positives" can vary from 0% to as
      much as 40%. The implication for the performing of "unnecessary" spine surgery is
      obvious. The thoughtful practitioner will be mindful of the role of psychosocial
      variables in so far as they are thought to be relevant in a particular case. The
      overall contribution of psychosocial variables to the application of
      interventional therapies for the diagnosis and treatment of pain can be
      overlooked and ignored, but not denied. A certain percentage of patients will
      respond in a predictable, desirable or positive fashion purely on a statistical
      basis. Historically, and there seems to be no reason to believe this will change
      in the immediate future, the degree to which the psychosocial variables are
      considered is left up to the interventionalist. Some are content to perform a
      directed procedure or therapy concerned only, and sometimes to a less than
      sufficient degree, with the technical adequacy of the procedure. Others will
      appreciate the role of human factors including those of the practitioner and
      patient alike, and strive not only for a statistically derived outcome but the
      best possible outcome for a given patient. Psychosocial factors can sometimes
      take on the character of "nuisance variables". However, it is hard not to wonder
      how much care each would want to have given to these factors if one were on the
      other end of the needle.

PMID- 14719719
TI  - Sacral neuromodulation for chronic pain conditions.
AB  - Some of the pelvic pain syndromes seem to have features of neurogenic
      inflammation and neuropathic pain in common. As opposed to being separate disease
      entities, they may represent a spectrum of clinical presentations of CRPS I of
      the pelvis. Sacral nerve root stimulation provides good symptomatic relief of
      pain and voiding dysfunction. The techniques of retrograde root stimulation may
      offer superior results with fewer complications and lead migrations when compared
      with other methods. Perhaps neuromodulation should be used earlier in the
      treatment paradigm for these disorders, before the potentially injurious
      procedures of hydrodistention, bladder installations, and cystectomies.

PMID- 14719720
TI  - Spinal cord stimulation for angina pectoris and peripheral vascular disease.
AB  - SCS is a viable option for treating angina pectoris and inoperable PVD. Its
      mechanism of action remains controversial, but successful pain relief has been
      consistently reported in various studies. Many clinicians are foregoing a formal
      trial, choosing instead to obtain an adequate area of paresthesia and implant in
      one session. Long-term follow-up of SCS patients treated for angina pectoris
      shows continued pain relief, increase in activities, and decreased use of
      medications. Emerging literature supports the finding that SCS is cost-effective
      in this patient population relative to CABG. SCS does not mask the ischemic pain
      that signals impending further damage of the myocardium. In patients with
      inoperable PVD, SCS relieves pain and improves microcirculatory blood flow.
      Quality of life and mobility can be improved with SCS. The beneficial effects of
      SCS on ulcer healing are controversial, and evidence suggests that the best
      candidates for the procedure are those with ischemic rest pain without tissue
      loss. Patients with diabetes mellitus and hypertension may have the least
      favorable outcomes with regard to limb salvage. No convincing data have been
      published on the cost-effectiveness of SCS in this patient population. SCS is a
      safe procedure that is minimally invasive, reversible, and associated with only
      infrequent side effects, the most common of which include lead migration and
      infection. SCS is clearly an option for the improvement of pain and the quality
      of life in this carefully selected subset of patients.

PMID- 14719721
TI  - Spinal analgesics.
AB  - The important issues to be emphasized when considering the intrathecal
      administration of novel analgesics are their proven antinociceptive effect,
      safety (short- and long-term effects on the spinal cord and potential
      toxicities), stability in shelf solution and at body temperature by itself, or in
      combination with other drugs in spinal fluid, compatibility with a long-term
      spinal infusion pump, whether they are of sufficiently high potency and
      solubility to be used in the finite volume of an implanted infusion pump, and if
      a pharmaceutical company is willing to invest the immense resources needed for US
      Food and Drug Administration approval and subsequent commercial development.

PMID- 14719722
TI  - A simple approach to outcomes assessment of the therapeutic and cost-benefit
      success rates for spinal cord stimulation therapy.
AB  - SCS was found to be cost-effective and therapeutically effective in this study
      for a majority of patients who had successful trial screening and were determined
      to be suitable candidates for SCS therapy. This is consistent with prior research
      if not slightly more encouraging, because typically half of the patients
      implanted with SCS reported 50% or more pain relief. Strikingly, most patients
      were considered cost successes. Overall, this study provides continued support
      that spinal cord stimulation offers the medical community an effective treatment
      for pain and reduces costs associated with the treatment of chronic intractable
      pain patients.

PMID- 14719723
TI  - The effect of pain on survival.
AB  - For patients suffering various diseases, increased pain hastens death by
      interfering with life-enhancing activities; if it hurts to eat, patients won't
      eat; if it hurts to move, they won't move. But survival simply cannot be enhanced
      by reducing pain because, even as some pain treatments have a beneficial effect
      on disease (spinal cord stimulation on coronary artery disease, for example),
      other pain treatments can have an adverse effect on survival. Thus, we must
      continue to investigate pain and its treatment even as we use the best possible
      techniques available to treat pain as aggressively as we would any other disease.

PMID- 14719724
TI  - The commoditization of orthodontics.

PMID- 14719725
TI  - Re: Perception of facial esthetics: a comparison of similar Class II cases
      treated with attempted growth modification or later orthognathic surgery. Angle
      Orthod. 2003;73:365-373.

PMID- 14719726
TI  - Growth modification of the rabbit mandible using therapeutic ultrasound: is it
      possible to enhance functional appliance results?
AB  - Previous studies have shown that functional appliances can enhance mandibular
      growth when applied during the active growth period. However, besides patient
      compliance problems with bulky appliances and prolonged treatment demands, there
      is contradictory evidence that functional appliances have a significant long-term
      effect. Is there a method to enhance the growth response and improve the long
      term success of functional appliances? Previous studies have also found that
      therapeutic ultrasound (US) can stimulate cartilage and bone growth. The
      objective of this study was to evaluate the effect of therapeutic US on condylar
      and mandibular growth in the rabbit model. Eight growing New Zealand male rabbits
      were chosen for this study. They received therapeutic US on one side of the
      mandible for 20 minutes/day for four weeks. Anthropometrical and histological
      evaluations revealed that US enhances mandibular growth by condylar endochondreal
      bone growth and consequently mandibular ramus growth. The significant results of
      this study support conducting a long-term study to evaluate the ultimate
      stability of the results obtained. Also, they suggest an extended research with a
      larger sample size and investigating the molecular basis of this stimulatory
      effect, together with forward posturing splints for optimal macroscopic and
      microscopic responses.

PMID- 14719727
TI  - The investigation of occlusal contacts during the retention period.
AB  - Removable retention appliances were applied to 20 treated orthodontic patients,
      and their occlusal contact points were determined from occlusal registrations
      taken at the beginning and the end of retention. Furthermore, to determine the
      results at the end of retention, the occlusion of 20 treated patients was
      compared with a control group of another 20 subjects who had an ideal occlusion.
      During the retention phase the number of contacts in centric occlusion increased
      significantly. No significant difference was observed with regard to the location
      of contacts. Whereas the number of ideally located contacts was similar to that
      in the control group, differences were observed in actual and canine contacts
      between the groups. At the end of retention, the balancing side contacts in
      lateral movements and the posterior contacts in protrusive movements were
      generally determined as near contacts and showed a similarity to the control
      group. In order to maintain the occlusal stability that is needed for the success
      of orthodontic treatments, ideal occlusal contacts and localization of contacts
      in centric and eccentric occlusion should be considered.

PMID- 14719728
TI  - The effect of mandibular protrusive (activator) appliances on articular eminence
      morphology.
AB  - In studying the response of the glenoid fossa to mandibular protrusive
      appliances, apart from the condyle, much attention has been focused on what
      happens to the posterior wall of the fossa (post-glenoid process). Remarkably,
      the articular eminence has been overlooked, although it is the most adaptive area
      of the temporomandibular joint. The purpose of this study was to explore the type
      of response of the articular eminence morphology to the use of mandibular
      propulsive appliances (activators). The study material consisted of individually
      corrected pre- and posttreatment lateral tomograms of 35 patients (18 boys and 17
      girls) who had been diagnosed as suitable for treatment with a mandibular
      protrusive appliance (activator). The tomograms were scanned and digitized on
      screen, and points located on each tomogram and linear measurements were used to
      evaluate any change in glenoid fossa morphology. Paired t-tests were applied
      separately for the left and right sides to compare pre- and posttreatment
      measurements. Paired t-tests were also applied to test any difference between the
      left and right sides. The results of this study show that there is no
      statistically significant change in articular eminence morphology (height and
      inclination) as a result of using mandibular protrusive appliances.

PMID- 14719729
TI  - Rapid maxillary expansion. Is it better in the mixed or in the permanent
      dentition?
AB  - The aim of this study was to compare the dentoskeletal effects of a modified
      acrylic-bonded rapid maxillary expansion (RME) device when it is used in the
      mixed and permanent dentitions. The study group consisted of 51 patients in the
      mixed and permanent dentition (26 girls and 25 boys) who underwent RME treatment.
      Group 1 was composed of 34 subjects in the mixed dentition (19 girls and 15 boys;
      mean age, 9.2 +/- 1.3 years). Group 2 consisted of 17 subjects in the permanent
      dentition (seven girls and 10 boys; mean age 12.7 +/- 1.2 years). Lateral and
      frontal cephalograms and upper dental casts were collected before treatment (T1),
      after treatment (T2), and after retention (T3). Intragroup and intergroup changes
      were evaluated by paired t-test and Student's t-test, respectively. In both
      groups after RME, the maxilla moved forward; mandible rotated posteriorly; facial
      height increased; nasal, maxillary, and maxillary intercanine and first molar
      widths increased; and the upper molars tipped buccally. Almost all these
      significant changes were stable at follow-up (T3). When overall (T1 - T3)
      differences were considered, upper molars tipped more, and the ANB angle
      increased less in the mixed dentition group compared with the permanent dentition
      group (P < .01). Within the limits of this study, the results suggest that the
      orthopedic effects of RME are not as great as expected at early ages, and it
      might be a better alternative to delay RME to early permanent dentition.

PMID- 14719730
TI  - Changes in lip, cheek, and tongue pressures after rapid maxillary expansion using
      a diaphragm pressure transducer.
AB  - The purpose of this study was to investigate the changes in pressures that are
      exerted to maxilla by the tongue, lip, and cheek before and after expansion and
      during the retention period. Twelve patients (five males, seven females) with
      maxillary transverse deficiencies were randomly selected. The first pressure
      measurements were made before expansion using a diaphragm pressure transducer.
      The second measurements were made right after the maxillary expansion procedure,
      which lasted about 20 days. The expansion devices were replaced with retention
      devices, and measurements were made at the end of the first, second, and third
      months of retention. Pressure values on the buccal side of upper first molar and
      incisor increased significantly right after expansion but started decreasing
      during retention. The values at the end of the third month of retention were
      similar to the preexpansion values (P < .05). Tongue pressures on the lingual
      side of the upper first molar and upper incisor decreased significantly with
      expansion but started increasing after the expansion procedure. Even at the end
      of the third month of the retention period, the values were not similar to the
      preexpansion values (P < .05). These values show that the cheeks and lips almost
      adapt to the new position of dental arches at the end of the third month, whereas
      tongue adaptation took comparatively longer.

PMID- 14719731
TI  - Rapid maxillary expansion and conductive hearing loss.
AB  - The purpose of this study was to evaluate the effects of rapid maxillary
      expansion (RME) on conductive hearing loss in 35 subjects (21 girls and 14 boys)
      with an average age of 14 years 6 months. All patients had maxillary constriction
      with a high palatal vault and a conductive hearing loss. Pure-tone audiometric
      records were used to determine the hearing levels at four time intervals, namely,
      before RME, after sufficient midpalatal suture opening was obtained (mean: 18
      days), after the retention period (mean: six months), and a final set two years
      after the retention period. Records were evaluated by the same otolaryngologist.
      Analysis of variance was used to assess the changes in the hearing level and the
      air-bone gap. Descriptive statistics were calculated for each subject at each
      period. The results indicated that significant changes occurred in both the
      hearing levels and air-bone gaps in both timing and frequency after the active
      treatment period (P < .001). For most patients (74%), these improvements were
      maintained two years after active treatment.

PMID- 14719732
TI  - Dental arch widths and mandibular-maxillary base widths in Class II malocclusions
      between early mixed and permanent dentitions.
AB  - The aim of the study was to analyze the transverse morphology and development of
      the dental arches and skeletal mandibular-maxillary bases in untreated Class II
      malocclusions. Using the records of the Belfast Growth Study, a Class II division
      1 group (II/1) and a Class II division 2 group (II/2) were compared with a Class
      I group and a control group with good occlusion. On posteroanterior cephalograms,
      maxillary skeletal base width and bigonial and biantegonial widths were
      determined at two-year intervals between seven and 15 years. Maxillary and
      mandibular intermolar widths were measured on the associated study casts. As a
      result, maxillary skeletal base widths were smallest in the Class II/1 subjects.
      No statistically significant differences were found among the groups for the
      skeletal mandibular widths. With respect to the development of the dental arches,
      maxillary intermolar widths were smaller in the Class II/1 group than in the
      Class I and the good-occlusion groups. These group differences were present for
      the total period of observation, ie, seven to 15 years, and statistically
      significant at most ages. When the relative difference between the maxillary and
      the mandibular intermolar widths was examined, the Class II/1 cases were found to
      have the largest average difference (about -2.5 mm for boys and -1.5 mm for
      girls), indicating a relatively narrow maxillary arch. Less pronounced molar
      differences were found in the Class II/2 group. In the Class II/1 subjects the
      deviations in molar differences observed at 15 years of age were established
      already at 7 years of age and maintained during 7 and 15 years of age.

PMID- 14719733
TI  - A comparative analysis of maxillary tooth movement produced by cervical headgear
      and pend-x appliance.
AB  - The purpose of this study was to compare the effects of cervical headgear and
      pend-x on the maxillary first molar, second molar, first premolar, and upper
      incisors. Cephalometric radiographs were obtained at the start of treatment (T1)
      and after molar distalization was completed (T2) for 13 patients in a pend-x
      group and 13 patients in a cervical headgear group. The changes of the maxillary
      teeth were measured on maxillary superimpositions. Nonparametric Mann-Whitney U
      test was used to compare the mean differences between the two groups. The mean
      amount of distalization for the headgear group was 3.15 +/- 1.94 mm and that for
      the pend-x group was 3.81 +/- 2.25 mm. The second molar teeth were also
      distalized to a mean amount of 2.27 +/- 1.33 mm in the headgear group and 2.04 +/
      2.15 mm in the pend-x group. The mean treatment time for distalization was 11.38
      +/- 3.18 months for the headgear group and 7.31 +/- 4.09 months for the pend-x
      group. During distalization, the maxillary molars tipped distally in both groups,
      but intergroup differences were not significant. The anterior inclinations of the
      first premolar and upper incisor increased significantly in the pend-x group (P <
      .01). Maxillary molars showed no vertical movement in the pend-x group but
      extruded in the headgear group (P < .01). The anchorage loss of the pend-x
      appliance as well as the necessary patient compliance and greater treatment time
      with the cervical headgear should be taken into consideration.

PMID- 14719734
TI  - Effects of thermocycling on the bond strength of a resin-modified glass ionomer
      cement: an in vitro comparative study.
AB  - This study investigated the effects of thermally induced stresses (thermocycling)
      on the shear bond strength of resin-modified, chemically cured, glass ionomer
      cement for use as an orthodontic bonding agent. A conventional no-mix composite
      resin was also used as a control. Mesh-based metal orthodontic brackets were
      bonded to extracted human premolars using either the resin-modified glass ionomer
      cement or the no-mix composite resin. Specimens were stored either in water at 37
      degrees C for 24 hours for baseline data or thermocycled between 5 degrees C and
      55 degrees C for 200 and 20,000 cycles before testing the in vitro shear bond
      strengths. Thermocycling reduced shear bond strengths for all specimens. The
      resin-modified glass ionomer cement showed a 11.1% decrease after 200
      thermocycles and 26.5% decrease after 20,000 thermocycles, whereas the no-mix
      adhesive resin showed only 5.7% and 17.9% reductions, respectively. Analysis of
      variance showed statistically significant differences between the mean shear bond
      strengths of the groups at the P < .001 level of significance. For the resin
      modified glass ionomer cement groups, the predominant bond failure site was at
      the bracket-adhesive interface. The results of this study suggest strongly that
      resin-modified glass ionomer cements offer a viable alternative to conventional
      no-mix composite resins, with satisfactory in vitro shear bond strength even
      after 20,000 thermocycles.

PMID- 14719735
TI  - In vitro evaluation of a moisture-active adhesive for indirect bonding.
AB  - The aim of this in vitro investigation was to evaluate bond strength for a
      cyanoacrylate adhesive in combination with an indirect bonding technique. Eighty
      bovine permanent mandibular incisors were randomly divided into four groups of 20
      teeth each. The influence of two factors on shear bond strength was investigated:
      (1) type of adhesive (Smartbond cyanoacrylate, Sondhi Rapid Set composite
      sealant) and (2) time of debonding (30 minutes and 24 hours after bonding).
      Stainless steel mesh-based brackets were used. Although, bond strength was not
      significantly different for the two debonding time periods, significantly lower
      bond strength measurements were found for the cyanoacrylate adhesive (P < .001).
      The mean bond strength for the cyanoacrylate adhesive group was 5.44 +/- 1.65 MPa
      for debonding 30 minutes and 6.92 +/- 1.48 MPa for debonding 24 hours after the
      bonding procedure vs 16.16 +/- 5.25 MPa and 14.98 +/- 2.85 MPa for the composite
      adhesive groups debonded at 30 minutes and 24 hours, respectively. The Weibull
      analysis indicated that there was an increased risk of bond failure at clinically
      relevant levels of stress for indirect bonding with the cyanoacrylate adhesive.

PMID- 14719736
TI  - Assessing the performance of a methyl methacrylate-based resin cement with self
      etching primer for bonding orthodontic brackets.
AB  - Questions over the usefulness of a self-etching primer with resin adhesive in the
      bonding of orthodontic brackets remain unsolved. The purpose of this study was to
      determine the effects of using Multibond, a new methyl methacrylate (MMA)-based
      resin cement with self-etching primer, on the shear bond strength of orthodontic
      brackets compared with Superbond C&B, which is a well-known MMA-based resin
      cement containing phosphoric acid etching. Metal or plastic brackets were bonded
      to etched or self-etching primed bovine teeth using Superbond C&B or Multibond.
      The shear bond strengths were measured after immersion in water at 37 degrees C
      for 24 hours. Data were analyzed by two-way analysis of variance and Scheffe's
      test. The surface appearances of the teeth after phosphoric acid etching or self
      etching priming were observed by field-emission scanning electron microscopy (FE
      SEM). Metal brackets bonded with Multibond had a significantly lower shear bond
      strength than metal brackets bonded with Superbond C&B. No significant
      differences in shear bond strength were observed between Multibond and Superbond
      C&B when plastic brackets were bonded to the enamel. The shear bond strength of
      metal brackets bonded with Multibond was comparable with that of plastic brackets
      bonded with Superbond C&B. Adhesive remnant index score showed a tendency of more
      residual resin cement remaining on the teeth when metal brackets were bonded with
      Multibond. FE-SEM observation revealed less dissolution of the enamel surface
      resulting from treatment with Multibond self-etching primer as compared with
      phosphoric acid. Thus, the Multibond system may be a candidate for bonding
      orthodontic brackets with the advantage of minimizing enamel loss.

PMID- 14719737
TI  - Crown-root shape of the permanent maxillary central incisor.
AB  - This study aimed to determine whether the lateral cephalometric crown-root shape
      differs among the permanent maxillary central incisor in Class I, Class II
      division 1, Class II division 2 and Class III malocclusions and to identify the
      nature of any differences. Of the 499 lateral cephalograms recorded at a
      university orthodontic clinic during 2001, 361 satisfied the inclusion criteria.
      Sixty cephalograms were selected from the four malocclusion groups and were
      digitized in random order. The configurations of the 10 landmarks characterizing
      the crown-root shape of the permanent maxillary central incisor were then
      optimally superimposed using Procrustes algorithms. Discriminant analysis of the
      principal components of shape determined the incisor shape differences between
      the malocclusion groups. The crown-root shape of the permanent maxillary central
      incisor did not differ significantly among the Class I, Class II division 1, and
      Class III groups (P > .05); however, the crown-root shape of the Class II
      division 2 permanent maxillary central incisor was significantly different (P <
      .001) from that of the Class 1, Class II division 1 and Class III. The shape
      discrimination involved axial bending of the Class II division 2 incisors.
      Principal components 1, 2, and 3 accounted for 63% of the Class II division 2
      incisor shape variance, encompassing a shorter root, a longer crown, and axial
      bending of the incisor, in addition to a reduced labiopalatal thickness. These
      shape features could precipitate the development of a deep overbite in Class II
      division 2 malocclusion and may limit the amount of palatal root torque during
      fixed appliance therapy.

PMID- 14719738
TI  - Skeletal and dental effects during observation and treatment with a magnetic
      device.
AB  - The aim of this study was to evaluate the effects of a magnetic appliance, MAD
      IV, on the treatment of anterior open bites in growing patients. The study
      material included the lateral cephalograms and hand-wrist radiographs of 16
      patients who had an anterior open bite malocclusion. The radiographs were taken
      at the beginning (T1) and at the end of observation period (T2) and at the end of
      MAD IV application (T3). At the beginning of the study, the mean age of the
      subjects was 11 years two months. To define the direction of facial growth, the
      patients were first observed for nine months without any orthodontic or
      orthopedic approach. At the end of the observation period, patients who had shown
      a vertical growth direction, resulting in an increase in open bite, were given an
      MAD IV appliance and were instructed to wear the appliance 18 hours a day for 7.5
      months. Thirty-two different parameters were evaluated from the lateral
      cephalograms. Paired t-tests were used for statistical evaluation of differences
      that occurred during the periods and between the periods. During the observation
      period, the patients continued their mandibular posterior rotation resulting in
      an increase in lower facial height (P < .001) and an open bite (P < .01). During
      the treatment period, the patients showed an anterior mandibular rotation with
      statistically important decreases in lower facial height and open bite (P <
      .001). In the treatment of anterior open bite with the MAD IV appliance, skeletal
      changes played a role along with dental and dentoalveolar effects.

PMID- 14719739
TI  - Management of alveolar clefts using dento-osseous transport distraction
      osteogenesis.
AB  - This article evaluates the usage of distraction osteogenesis (DO) in the
      treatment of cleft alveoli. The procedure was carried out on eight alveolar
      clefts of five patients between the ages of 17 and 25 years. Three patients had
      bilateral alveolar clefts (BAC) and two patients had unilateral alveolar clefts
      (UAC). DO was carried out bilateral to the palatal segments for the BAC patients
      and unilateral to the lesser segment for the UAC patients. A custom-made tooth
      borne distractor was used. The average amount of distraction was eight mm (range,
      5-11.5 mm). The average amount of distal movement of the anchorage teeth was 0.8
      mm (range, 0-2 mm). The average amount of inclination changes of the transport
      segments and anchorage teeth was 7.6 degrees (range, 2-17.5 degrees) and 3.3
      degrees (range, 0-9 degrees), respectively. Two important problems were observed
      attributable to the method. First, the transport segment was docked in a more
      superior position at the end of distraction process. This undesirable movement
      also changed the inclination of the teeth in the transport segment and increased
      tooth tipping. Removing the device in the second week of the consolidation period
      and retracting the segment to its ideal position orthodontically solved these
      problems. Second, the bony defect on the nasal side of the alveolar cleft could
      not be completely closed. This method for repairing small or large alveolar
      clefts is a simple, cost-effective, and useful treatment option. However,
      repairing the alveolar cleft without grafts seems to be impossible when using a
      tooth-borne device.

PMID- 14719740
TI  - Anchorage loss--a multifactorial response.
AB  - Anchorage loss (AL) is a potential side effect of orthodontic mechanotherapy. In
      the present study, it is defined as the amount of mesial movement of the upper
      first permanent molar during premolar extraction space closure. In addition, AL
      is described as a multifactorial response in relation to the extraction site,
      appliance type, age, crowding, and overjet. For this study, 87 university clinic
      and private practice subjects, who were defined as maximum anchorage cases and
      had undergone bilateral maxillary premolar extractions, were divided into four
      groups according to extraction site (first vs second premolars), mechanics
      (lingual vs labial edgewise appliances), and age (adolescents vs adults). Overjet
      and crowding were examined from the overall sample. Data were collected from
      serial lateral cephalograms and dental casts. The results showed that as the
      severity of dental crowding increased, AL significantly decreased (r = -0.66, P =
      .001). Labial edgewise appliances demonstrated a significantly greater AL than
      did lingual edgewise appliances (1.15 +/- 2.06 mm, P < .05). A greater, though
      not statistically significant, AL was found in adults than in adolescents (0.73
      +/- 1.43 mm). There was a slight nonsignificant increase in AL between maxillary
      second compared with first premolar extractions (0.51 +/- 1.33 mm). Overjet was
      weakly correlated to AL. These results suggest that AL is a multifactorial
      response and that the five examined factors can be divided into primary
      (crowding, mechanics) and secondary factors (age, extraction site, overjet), in
      declining order of importance.

PMID- 14719741
TI  - Intrabony migration of impacted teeth.
AB  - Intrabony migration of impacted teeth is a rare dental anomaly, which occurs only
      in the permanent dentition of the lower jaw. The teeth involved in this
      phenomenon are the mandibular lateral incisor, canine, and second premolar.
      Migration of the lateral incisor is usually in a distal direction, resulting in
      transposition with the canine. Migration of the canine is most frequently in a
      mesial direction, resulting in transmigration across the mandibular symphysis to
      the opposite side of the dental arch. The second premolar most often migrates
      distally, sometimes past the gonial angle and as far as the coronoid process.
      Surgical and orthodontic treatment options are presented for the three intrabony
      migrating teeth.

PMID- 14719742
TI  - Spontaneous correction of Class II malocclusion after rapid palatal expansion.
AB  - A case of a Class II, division 1 malocclusion with reduced transpalatal width is
      reported. The only treatment provided for this patient was rapid palatal
      expansion. After expansion, the mandible seemed to be carried forward to its
      normal position, resulting in a spontaneous correction of the Class II
      malocclusion. This case report illustrates the outcome of the method of treatment
      used with a long-term (14-year posttreatment) follow-up.

PMID- 14719743
TI  - Transmigration of mandibular canines--a review of the literature and a report of
      five cases.
AB  - Transmigration of the mandibular permanent canine is a rare event, the etiology
      of which is not clear. We present five cases of transmigrated mandibular canines
      together with a review of the literature, a discussion of the etiology, and the
      treatment options.

PMID- 14719744
TI  - Orthodontic and orthopedic treatment of a patient with incontinentia pigmenti.
AB  - Incontinentia pigmenti is an uncommon, inherited disorder with predominantly
      ectodermal manifestations that is associated with skin (100%)), dental (90%),
      skeletal (40%), central nervous (40%), and ocular (35%) deformities. It is an X
      linked dominant disease, usually lethal in males and occurring in female infants.
      The dental effects include delayed eruption, partial anodontia, microdontia, and
      cone or peg-shaped teeth. The dental, clinical, and radiological findings in a 16
      year-old female are presented here. The patient had peg-shaped teeth and a
      unilateral maxillary transverse discrepancy associated with oligodontia in the
      maxillary and mandibular arches. Orthodontic treatment included rapid maxillary
      expansion and fixed orthodontic therapy for prosthetic purposes and elimination
      of the functional midline shift.

PMID- 14719745
TI  - "Out of our crisis": the lack of long-term relationships in the provision of
      managed care.
AB  - During the thirty-year period between 1965 and 1995, national healthcare
      expenditures rose significantly to a point where it became an untenable situation
      for any payer class: patient, employer, or government. Although managed care was
      offered as a conceptual framework for providing an opportunity for improving the
      health of the population while limiting the growth in expenditures, significant
      concern remained regarding the perceived quality of care and the underlying
      incentive structures. The author examines current healthcare incentive structures
      and proposes a structural model associated with long-term contracting to allow
      managed care to attain its intended objectives of enhanced quality and cost
      containment.

PMID- 14719746
TI  - Does attribution theory explain physicians' nonacceptance of clinical practice
      guidelines?
AB  - Clinical practice guidelines can potentially lead to reductions in healthcare
      costs and improved patient outcomes if adopted by physicians into their clinical
      practice. This research study provides data that gives healthcare administrators
      a basic understanding of how physicians perceive clinical practice guidelines
      (CPGs) and gives practical suggestions to obtain physician adherence to CPGs.

PMID- 14719747
TI  - A fragmented patient safety concept: the structure and culture of safety
      management in healthcare.
AB  - Safety in healthcare organizations is often an ownerless process with
      responsibility falling under a myriad of departments that individually are
      coordinating initiatives to improve aspects of safety. In contrast, other high
      hazard industries seek to institutionalize safety management as a key
      characteristic of organizational culture. Healthcare seeks to model its approach
      to patient safety on other high-hazard industry models, but without an
      understanding of the impact of creating a uniform approach to safety management,
      healthcare organizations will not implement a similar organization-wide safety
      culture.

PMID- 14719748
TI  - The Centers for Medicare and Medicaid Services proposal to pay for performance.

PMID- 14719749
TI  - African American participation in clinical trials: recruitment difficulties and
      potential remedies.

PMID- 14719750
TI  - 2020 vision: what will you be treating in 20 years?

PMID- 14719751
TI  - Risk data availability.

PMID- 14719752
TI  - Thoughts on temporomandibular joint pain.

PMID- 14719753
TI  - When the time comes, do you expect to be ready for retirement?

PMID- 14719754
TI  - Clinical evaluation of packable and conventional hybrid resin-based composites
      for posterior restorations in permanent teeth: results at 12 months.
AB  - BACKGROUND: Packable resin-based composites and simplified resin bonding systems
      are marketed to offer many advantages over conventional posterior hybrid
      composites and total-etch bonding systems. The authors conducted a study to
      evaluate the initial clinical performances of a packable and a conventional
      hybrid resin-based composite used with a simplified bonding system. METHODS: A
      total of 57 Class I and 45 Class II restorations were placed in the permanent
      teeth of 65 adult patients. The carious lesions were restored with either
      packable resin-based composite (SureFil, Dentsply DeTrey GmbH, Konstanz, Germany)
      or conventional hybrid resin-based composite (SpectrumTPH, Dentsply DeTrey GmbH),
      using a resin adhesive (Non-Rinse Conditioner and Prime & Bond NT, both
      manufactured by Dentsply DeTrey GmbH). The authors evaluated the restorations
      using U.S. Public Health Service-Ryge modified criteria (in which Alfa is the
      highest rating) and by using color transparencies and die stone replicas.
      RESULTS: Three SureFil restorations failed before their baseline evaluation.
      There were no failures among the 78 SpectrumTPH restorations evaluated at 12
      months. For both resin-based composites, Alfa ratings were 90 percent or higher
      for marginal discoloration, anatomical form, surface texture and surface
      staining. Lower percentages of restorations were rated Alfa for color match,
      marginal integrity and gingival health. Occasional mild postoperative sensitivity
      was reported for four SureFil restorations and one SpectrumTPH restoration. The
      mean occlusal wear rate was 38 micrometers for the larger SureFil restorations
      and 25 microm for the smaller SpectrumTPH restorations. CONCLUSIONS: The 12-month
      clinical performances of the two restorative materials were satisfactory and not
      significantly different for each of the parameters evaluated. CLINICAL
      IMPLICATIONS: A packable and a conventional hybrid resin-based composite placed
      with a simplified bonding system in posterior permanent teeth showed satisfactory
      and similar results after 12 months.

PMID- 14719755
TI  - A prospective study of social support, anger expression and risk of periodontitis
      in men.
AB  - BACKGROUND: Stress is associated with poor oral hygiene, increased glucocorticoid
      secretion that can depress immune function, increased insulin resistance and
      potentially increased risk of periodontitis. METHODS: The authors examined the
      association between social support, anger expression and periodontitis in 42,523
      male, U.S.-based, health professionals. Subjects were aged 40 to 75 years in
      1986, and more than half were dentists. The men were free of a diagnosis of
      periodontitis at the start of follow-up in 1996. RESULTS: Subjects who reported
      having at least one close friend had a 30 percent lower risk of developing
      periodontitis compared with those who did not have a close friend (relative risk,
      or RR = 0.70; 95 percent confidence interval, or CI, 0.51-0.96). Men who
      participated in religious meetings or services had a 27 percent lower risk of
      developing periodontitis compared with men who did not participate in religious
      meetings (RR = 0.73; 95 percent CI, 0.64-0.83). After the authors adjusted for
      potential confounding variables, men whose anger scores were in the top quintile
      were 72 percent more likely to report having periodontitis compared with men
      whose scores were in the lowest quintile (RR = 1.72; 95 percent CI, 1.39-2.12).
      Men who reported being angry on a daily basis had a 43 percent higher risk of
      developing periodontitis compared with men who reported being angry seldom.
      CONCLUSION: Reduced social isolation and anger expression may play an important
      role in maintaining oral health, as well as general health and well-being.
      CLINICAL IMPLICATIONS: When treating patients with periodontitis, clinicians
      should be cognizant of the social and behavioral factors that may affect oral
      health.

PMID- 14719756
TI  - Assessing revascularization of avulsed permanent maxillary incisors by laser
      Doppler flowmetry.
AB  - BACKGROUND: Laser Doppler flowmetry, or LDF, is a noninvasive method used to
      assess pulpal blood flow, or PBF. Dental avulsion is associated with loss of
      pulpal sensitivity. The authors conducted this study to assess whether LDF could
      be used to detect revascularization of replanted teeth. METHODS: The authors used
      LDF to assess the PBF values of avulsed permanent maxillary incisors treated
      using replantation and splinting in 17 subjects. They took measurements at four
      sessions: on the day of splint removal and at 12 weeks, 24 weeks and 36 weeks
      after splint removal. Five vital control teeth and five nonvital control teeth
      were used to assess the background signal. At 36 weeks, the authors determined
      clinically and radiographically whether revascularization had occurred. RESULTS:
      LDF readings correctly predicted the pulp status in 88.2 percent of the readings.
      Of the readings for vital teeth, 100 percent were correct, and of the readings
      for nonvital teeth, 80 percent were correct. Univariate analysis of variance
      demonstrated that in revascularized teeth, the PBF value increased significantly
      from splint removal to week 12 after splint removal and from week 24 to week 36
      after splint removal. In the teeth that failed to revascularize, the PBF value
      dropped significantly from week 24 to week 36 after splint removal. CONCLUSIONS:
      The results of this study suggest that LDF accurately diagnoses revascularization
      of avulsed maxillary incisors after replantation and splinting. CLINICAL
      IMPLICATIONS: LDF may become useful in detecting revascularization much earlier
      than standard sensitivity tests.

PMID- 14719757
TI  - Preventing musculoskeletal disorders in clinical dentistry: strategies to address
      the mechanisms leading to musculoskeletal disorders.
AB  - BACKGROUND: The authors reviewed studies to identify methods for dental operators
      to use to prevent the development of musculoskeletal disorders, or MSDs. TYPES OF
      STUDIES REVIEWED: The authors reviewed studies that related to the prevention of
      MSDs among dental operators. Some studies investigated the relationship between
      the biomechanics of seated working postures and physiological damage or pain.
      Other studies suggested that repeated unidirectional twisting of the trunk can
      lead to low back pain, while yet other studies examined the detrimental effects
      of working in one position for prolonged periods. Additional studies confirmed
      the roles that operators' flexibility and core strength can play in balanced
      musculoskeletal health and the need for operators to know how to properly adjust
      ergonomic equipment. RESULTS: This review indicates that strategies to prevent
      the multifactorial problem of dental operators' developing MSDs exist. These
      strategies address deficiencies in operator position, posture, flexibility,
      strength and ergonomics. Education and additional research are needed to promote
      an understanding of the complexity of the problem and to address the problem's
      multifactorial nature. CLINICAL IMPLICATIONS: A comprehensive approach to address
      the problem of MSDs in dentistry represents a paradigm shift in how operators
      work. New educational models that incorporate a multifactorial approach can be
      developed to help dental operators manage and prevent MSDs effectively.

PMID- 14719758
TI  - Managing slightly uncooperative pediatric patients.

PMID- 14719759
TI  - Radiation-induced heart disease after Hodgkin's disease and breast cancer
      treatment: dental implications.
AB  - BACKGROUND: People with Hodgkin's disease and breast cancer often receive
      therapeutic irradiation to the chest (mediastinum) as an element of treatment.
      While the therapy often cures the malignancy, it has been implicated in causing
      late-onset heart disease that may influence the provision of dental treatment.
      TYPE OF STUDIES REVIEWED: The authors conducted a MEDLINE search of the years
      1995 through 2002 using the key terms "Hodgkin's disease," "breast cancer,"
      "radiation therapy," "cardiac valves" and "coronary artery" to define the
      pathophysiology of the disorder, its epidemiology and dental implications. The
      articles they selected for further review included those published in English in
      peer-reviewed journals. RESULTS: Therapeutic irradiation of the chest results in
      the inadvertent inclusion of the heart within the irradiation field. Over the
      next 10 to 20 years, some of these people may experience pathological changes of
      the heart valves that could predispose them to endocarditis, accelerated
      atherosclerosis of the coronary artery that heightens their risk of experiencing
      a fatal myocardial infarction or both. CLINICAL IMPLICATIONS: Dentists need to
      identify patients who have received therapeutic irradiation to the chest and
      consult with the patients' physicians to determine whether the therapy has
      damaged the heart valves or coronary arteries. Patients with radiation-induced
      valvular disease may require prophylactic antibiotics when undergoing specific
      dental procedures that are known to cause a bacteremia and a heightened risk of
      developing endocarditis. Patients with radiation-induced coronary artery disease
      should be administered only limited amounts of local anesthetic agents containing
      a vasoconstrictor, and they may require the administration of sedative agents and
      cardiac medications to preclude ischemic episodes.

PMID- 14719760
TI  - Total-etch versus self-etch adhesive: effect on postoperative sensitivity.
AB  - BACKGROUND: Self-etching adhesives are believed to prevent postoperative
      sensitivity when used under posterior resin-based composite restorations. The
      authors tested a twofold hypothesis: a self-etch, or SE, adhesive would result in
      less postoperative sensitivity than a total-etch, or TE, adhesive; an SE adhesive
      would result in poorer enamel marginal integrity than a TE adhesive. METHODS:
      Patients were selected on the basis of requiring Class I and II restorations in
      molars and premolars. The authors placed 30 restorations with the SE material
      (Clearfil SE Bond, Kuraray America, New York) and 36 restorations with Prime &
      Bond NT (Dentsply Caulk, Milford, Del.), which uses 34 percent phosphoric acid to
      etch enamel and dentin simultaneously. Preparations were of standard design, with
      all margins in enamel without beveling. Upon rubber dam isolation, the authors
      conditioned the enamel and dentin walls with the self-etching primer (for
      Clearfil SE Bond) or etched with the proprietary 34 percent phosphoric acid (for
      Prime & Bond NT), followed by application of the corresponding dentin adhesive.
      Teeth were restored with the proprietary hybrid resin-based composite indicated
      for posterior restorations: Clearfil AP-X for Clearfil SE Bond or Esthet-X Micro
      Matrix Restorative for Prime & Bond NT. The restored teeth were evaluated
      preoperatively and at two weeks, eight weeks and six months postoperatively for
      sensitivity to cold (ice), air and masticatory forces, as well as for marginal
      discoloration. RESULTS: Analysis of variance revealed no statistically
      significant differences in postoperative sensitivity between the SE and TE
      materials at any recall time. Marginal discoloration was rated as "absent" for
      all restorations at six months. Only one tooth displayed sensitivity to occlusal
      forces at six months. CONCLUSION: The SE adhesive did not differ from the TE
      adhesive in regard to sensitivity and marginal discoloration. CLINICAL
      IMPLICATIONS: Postoperative sensitivity may depend on the restorative technique
      rather than on the type of dentin adhesive used.

PMID- 14719761
TI  - Access to dental care for children in the United States: a survey of general
      practitioners.
AB  - BACKGROUND: In response to concern that inadequate dental school training may
      create a barrier to access to care for children, the authors conducted a survey
      concerning general practitioners' practice patterns involving child patients.
      METHODS: The authors requested a list of 4,970 randomly chosen general
      practitioners from the American Dental Association Survey Center. They then sent
      those dentists a written survey asking whether and in what numbers they treat
      children; the ages and caries levels of any children they do treat; their
      perceptions of their educational experiences in pediatric dentistry, and their
      perceived needs for continuing education in pediatric dentistry. They analyzed
      data using chi2. RESULTS: Ninety-one percent of the general dentists surveyed
      treated children, but those younger than 4 years of age, with high levels of
      caries, and whose care is funded by Medicaid were represented in very low
      numbers. The types of patients treated and procedures performed by the
      respondents were significantly (P < or = .05) associated with the intensity of
      the respondents' educational experiences, except for the number and types of
      Medicaid patients they treated. CONCLUSIONS: These data indicate that the vast
      majority of general practitioners treat children in their practices, but there
      still are groups of children for whom access to dental care is a problem.
      PRACTICE IMPLICATIONS: Very young children, children with high levels of caries
      and Medicaid-covered children have difficulty finding dental care in the general
      practice community.

PMID- 14719762
TI  - Magnification in dentistry: useful tool or another gimmick?
AB  - In spite of their significant cost, the relatively long learning curve associated
      with their use, frustrations during use, their occasional need for being replaced
      and their peculiar appearance to patients, magnifying loupes assist all types of
      clinical dentists in producing higher-quality dentistry. Seeing better also means
      decreasing operating time. Properly fitted loupes also can improve posture during
      operating and reduce muscle pain in the shoulders, neck and back. Working under
      magnification is useful, and clinicians should give strong consideration to
      adopting the concept.

PMID- 14719763
TI  - ERISA pre-empts patient's negligence claim against HMO.

PMID- 14719764
TI  - Creating a viable practice vision.
AB  - Vision guides the long-term development and growth of a dental practice. It
      provides focus and purpose to the dentist and team and creates clear goals for
      achieving practice growth and moving toward realizing the vision.

PMID- 14719765
TI  - For the dental patient. Sensitive teeth: causes and treatment.

PMID- 14719766
TI  - Clinical problems with developmental anomalies of the biliary tract.
AB  - Cholestatic jaundice defined as conjugated hyperbilirubinemia is a typical
      feature of neonatal liver disease. Biliary atresia is the most common disorder
      producing cholestasis during the first 2 months of life. Syndromic and non
      syndromic paucity of the intralobular bile ducts and choledochal cysts can also
      present with cholestasis during early life. Liver dysfunction from obstruction of
      the biliary tree must be differentiated from numerous disorders affecting
      hepatocytes such as congenital infection and inborn errors of metabolism. Early
      recognition and a stepwise diagnostic evaluation of the cholestatic infant are
      essential in successfully treating many metabolic and infectious liver diseases
      of the infant as well as surgically relieving obstruction in patients with
      biliary atresia.

PMID- 14719767
TI  - Gallstone disease and its complications.
AB  - Gallstone disease is one of the most common disorders of the gastrointestinal
      tract, and more cholecystectomies are performed each year in the United States
      than any other elective abdominal operation. As such, clinicians need a
      fundamental knowledge of gallstone disease and the common complications that are
      associated with this disease. Overall, the prevalence of gallstones in the United
      States is approximately 10% to 15%, of which, approximately 80% are without
      symptoms. Symptoms will occur in approximately 20% of those with gallstones, and
      this subgroup is at the highest risk for developing serious complications from
      their gallstone disease. These complications can range from simple recurrent
      biliary colic to severe, life-threatening ascending cholangitis and/or
      pancreatitis. This review will outline the basis for gallstone formation, the
      underlying mechanisms that result in gallstone-induced symptoms and a rational
      approach to individuals who present with symptoms consistent with gallstone
      disease. Current diagnostic and treatment modalities will be discussed, with a
      particular emphasis on acute cholecystitis and acute biliary pancreatitis.

PMID- 14719768
TI  - Gallbladder polyps, cholesterolosis, adenomyomatosis, and acute acalculous
      cholecystitis.
AB  - Acute acalculous cholecystitis is characterized by acute inflammation of the
      gallbladder in the absence of stones, usually occurring in elderly and critically
      ill patients with atherosclerosis, recent surgery or trauma, or hemodynamic
      instability. Patients may present with only unexplained fever, leukocytosis, and
      hyperamylasemia without right upper quadrant tenderness. If untreated, rapid
      progression to gangrene and perforation occurs. Surgical cholecystectomy and
      cholecystostomy provide the most definitive treatment although recent studies
      indicate success with percutaneous or endoscopic cholecystostomy. Cholesterolosis
      and adenomyomatosis of the gallbladder are usually clinically silent and
      incidental findings at the time of cholecystectomy. Cholesterolosis is
      characterized by mucosal villous hyperplasia with excessive accumulation of
      cholesterol esters within epithelial macrophages. Usually clinically silent, the
      condition rarely is associated with biliary symptoms or idiopathic pancreatitis
      and cannot reliably be detected by ultrasonography. Adenomyomatosis describes an
      acquired, hyperplastic lesion of the gallbladder characterized by excessive
      proliferation of surface epithelium with invaginations into a thickened
      muscularis propria. Ultrasonography may reveal a thickened gallbladder wall with
      intramural diverticula. Adenomyomatosis may portend a higher risk of gallbladder
      malignancy. Most cases of cholesterolosis and adenomyomatosis identified by
      imaging require no specific treatment. Gallbladder polyps include all mucosal
      projections into the gallbladder lumen and include cholesterol polyps,
      adenomyomas, inflammatory polyps, adenomas, and other miscellaneous polyps. Most
      polyps are nonneoplastic and rarely cause symptoms. Cholecystectomy is advocated
      for polyps greater than 10 mm in size because of increased risk of adenomatous or
      carcinomatous features.

PMID- 14719769
TI  - Primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver
      disease of uncertain etiopathogenesis commonly associated with inflammatory bowel
      disease (IBD) and is characterized by patchy inflammation of the biliary tree
      progressing to fibrosis and strictures. The natural history of PSC is highly
      variable but characteristically follows a progressive clinical course leading to
      biliary tree strictures, cholestasis, and choledocholithiasis. The course of the
      disease may be complicated by cholangitis, secondary biliary cirrhosis, liver
      failure, and cholangiocarcinoma. The diagnosis of PSC is based on typical
      cholangiographic findings, supported by nonspecific clinical signs and symptoms,
      cholestatic liver biochemical tests, and liver biopsy. Uncommon and usually
      clinically obvious secondary causes of sclerosing cholangitis are excluded before
      establishing the diagnosis of PSC. Therapeutic approaches that show promise
      include endoscopic therapy and ursodeoxycholic acid. The only accepted therapy
      for end-stage PSC that can improve long-term outcome is liver transplantation.
      The diagnosis of cholangiocarcinoma--often difficult and elusive--usually
      precludes liver transplantation because its prognosis is very poor.

PMID- 14719770
TI  - Motility and dysmotility of the biliary tract.
AB  - Muscle fibers in the biliary tree, and therefore the potential for dysmotility,
      are located in the gallbladder and the sphincter of Oddi. Dysmotility at either
      site is a potential cause of biliary pain in the absence of stones, although
      significant controversy persists. Diminished gallbladder emptying measured by
      biliary scintigraphy is an indication for cholecystectomy, although studies are
      contradictory regarding clinical benefit. It is likely that careful selection of
      patients for cholescintigraphic testing, many of whom have had missed stones or
      sludge, will identify patients who benefit from cholecystectomy. However, given
      the increased incidence of gallbladder stasis in functional gastrointestinal
      disorders, wide use of this study in patients with abdominal symptoms leads to a
      frequent failure to respond to cholecystectomy. Sphincter of Oddi dysfunction
      (SOD) has been best studied in patients with biliary type pain who have had prior
      cholecystectomy. Much less understood is the association of SOD with idiopathic
      recurrent acute pancreatitis and chronic pancreatitis. The least-studied clinical
      association for SOD is in patients with biliary pain and intact gallbladders.
      Elevated basal sphincter of Oddi pressure is predictive of clinical response to
      sphincterotomy in patients with postcholecystectomy pain in two randomized sham
      controlled studies. However, patients with suspected SOD have the highest
      complication rate from endoscopic retrograde cholangiogram and sphincterotomy,
      and, therefore, careful patient selection is mandatory.

PMID- 14719771
TI  - Tumors of the gallbladder, bile ducts, and ampulla.
AB  - Neoplasms arising in the gallbladder, bile ducts, and ampulla of Vater pose a
      significant clinical challenge. Although benign neoplasms may be encountered, the
      majority of these tumors are malignant. There are a number of similarities among
      tumors at these sites including their clinical presentation which may include
      biliary obstruction. Furthermore, these tumors are often asymptomatic early in
      their course and frequently present at an advanced stage of disease, precluding
      potentially curative resection. This article focuses on the diagnosis, staging,
      and operative management of gallbladder, bile duct, and ampullary tumors, with a
      specific focus on malignant disease.

PMID- 14719772
TI  - Endoscopic and radiologic management of pancreatic and biliary tract diseases.
AB  - Therapeutic biliary and pancreatic endoscopy has evolved over the last 30 years
      to a level where it represents the primarily mode of therapy for many frequently
      encountered diseases of the bile ducts liver and pancreas. The complication rates
      are expected to be low and the expectations of our colleagues are high. The
      endoscopist is expected to understand the origin and natural history of these
      diseases and the consequences of the various management options. The training of
      the endoscopist has taken on a very formal character, as has the emphasis on
      competency and quality improvement. The appearance of minimally invasive surgery
      and advanced imaging does not represent a threat to the biliary endoscopist but
      rather is complimentary and assists us so that unnecessary potentially morbid
      procedures are not done unnecessarily. The appearance of a new specialty: the
      minimally invasive biliary interventionalist, who would receive training by
      gastroenterologists, interventional radiologist and biliary-pancreatic surgeons,
      is the logical next step!

PMID- 14719773
TI  - Surgical management of gallstone disease and postoperative complications.
AB  - Symptomatic gallstone disease is one of the most common illnesses requiring
      surgical therapy. In the United States, an estimated 700,000 people will undergo
      cholecystectomy for gallstones this year. The average patient has an
      uncomplicated postoperative course and is satisfied with the results of
      treatment. However, complications do occur and the prudent clinician should have
      a clear understanding of their causes, prevention, recognition, and the
      management strategies for their successful resolution. These issues are reviewed
      in the this article.

PMID- 14719774
TI  - Perceptual sensitivity and motoric competence in 5- and 6-month-old infants.
AB  - The authors explored whether 5- to 6-month-old infants were sensitive to
      perceptual information and how they used perception as a recognition cue to
      search for a hidden object. In addition, the authors categorized and examined
      infant grasp by developmental effectiveness to determine any impact on infant
      search behaviors. In a within-participants design, 20 infants were presented with
      a toy in 2 occluder conditions. The toy was hidden under either a thick,
      camouflaging cloth or a thin, semitransparent cloth. The data revealed
      significant effects of perceptual sensitivity, age, and motor sophistication on
      search tasks. The results suggest that motor competence might be a limiting
      factor in infants' abilities to link motoric responses to notions about an
      object.

PMID- 14719775
TI  - The influence of temperamental reactivity and situational context on the emotion
      regulatory abilities of 3-year-old children.
AB  - Although much research has been conducted on emotion regulation, little work in
      the preschool period has examined the interrelationships between emotion
      regulation, temperamental reactivity, and situational context. The authors
      investigated the temperamental dispositions of fifty-three 3-year-old children
      (27 boys, 26 girls) and their behavioral responses to several challenging tasks
      (i.e., stranger-approach situation, busy-caregiver paradigm, and delay-of
      gratification task). Results indicated that both situational context and
      temperamental reactivity influenced the type of emotion-regulatory strategy used
      and that those relationships were best understood within a developmental
      framework. Moreover, the authors found that girls displayed more comforting
      strategies, suggesting that gender differences in emotion regulation may exist.

PMID- 14719776
TI  - Low-income preschoolers' false-belief performance.
AB  - A group of 72 preschoolers (36 African Americans, 36 European Americans) enrolled
      in Head Start programs and other preschools serving low-income children were
      asked 3 variations of false-belief questions across 3 scenarios and given a
      language and cognition subtest. Children's performance varied across the
      questions and tasks, but after covarying for children's language and cognitive
      scores, those effects were no longer found to be significant. Age effects were
      still significant even after differences in children's language and cognitive
      abilities had been accounted for. Although no language and cognitive differences
      were found among European Americans and African Americans, the European Americans
      still outperformed African Americans on 1 of the task scenarios. Those results
      demonstrate (a) the importance of considering testing procedures and language and
      cognitive abilities when assessing children's social cognitive skills and (b)
      that age-related changes in false-belief understanding are associated with social
      cognitive conceptual changes that are independent of language and cognitive
      skills.

PMID- 14719777
TI  - The speech and vocalization patterns of boys with ADHD compared with boys with
      dyslexia and boys without learning disabilities.
AB  - This research study dealt with an inquiry into the speech and vocalization
      patterns of boys with Attention Deficit Hyperactivity Disorder (ADHD) who were
      not under the influence of stimulating medication, compared with the speech and
      vocalization patterns of boys with reading disabilities and a control group of
      learners without learning disabilities. The voices of 105 participants were
      recorded during interviews and analyzed in the laboratory using equipment that
      examined the temporal speech patterns and physical features of vocalization. The
      speech patterns were examined with a frequency examination, speech unit length
      duration, and correlation between the vocalization and pauses in the speech unit.
      The physical features of vocalization were examined with volume and frequency
      scales. The research results indicated that the speech and vocalization patterns
      of boys with ADHD were significantly different from those of boys with reading
      disabilities and from the boys in the control group. The results support the
      assumption that speech and vocalization indicators can be used as objective
      indicators for the diagnosis of hyperactivity syndrome with attention and
      concentration difficulties.

PMID- 14719778
TI  - Preadolescents' recognition of faces of unfamiliar peers: the effect of
      attractiveness of faces.
AB  - The authors examined preadolescents' ability to recognize faces of unfamiliar
      peers according to their attractiveness. They hypothesized that highly attractive
      faces would be less accurately recognized than moderately attractive faces
      because the former are more typical. In Experiment 1, 106 participants (M age =
      10 years) were asked to recognize faces of unknown peers who varied in gender and
      attractiveness (high- vs. medium-attractiveness). Results showed that
      attractiveness enhanced the accuracy of recognition for boys' faces and impaired
      recognition of girls' faces. The same interaction was found in Experiment 2, in
      which 92 participants (M age = 12 years) were tested for their recognition of
      another set of faces of unfamiliar peers. The authors conducted Experiment 3 to
      examine whether the reason for that interaction is that high- and medium
      attractive girls' faces differ more in typicality than do boys' faces. The effect
      size of attractiveness on typicality was similar for boys' and girls' faces. The
      overall results are discussed with reference to the development of face encoding
      and biological gender differences with respect to the typicality of faces during
      preadolescence.

PMID- 14719779
TI  - Emotional autonomy and problem behavior among Chinese adolescents.
AB  - The author examined the association between emotional autonomy and problem
      behavior among Chinese adolescents living in Hong Kong. The respondents were 512
      adolescents, 16 to 18 years of age, who were interviewed for a cross-sectional
      study. Three dimensions of emotional autonomy including individuation,
      nondependency on parents, and de-idealization of parents were significantly and
      positively correlated with the amount of problem behavior the participants
      engaged in during the past 6 months. Using a simple linear multiple regression
      model, the author found that problem behavior was associated with only one aspect
      of emotional autonomy-individuation. Results indicated that the relationship
      between problem behavior and three aspects of emotional autonomy was similar in
      both individualistic and collectivistic societies.

PMID- 14719780
TI  - Relationship of recalled parenting style to self-perception in Korean American
      college students.
AB  - The authors examined the relationship of authoritarian, authoritative, and
      permissive parenting styles and the number of years in the United States with
      self-perception (academic competence, morality, and self-reliance) as recalled by
      Korean American college students (N = 144). Authoritative parenting behaviors
      were most common in Korean American families, followed by authoritarian
      behaviors, with permissive behaviors a distant 3rd. Authoritative parenting
      styles and the number of years lived in the United States were predictive of
      higher academic competence. Authoritarian and permissive parenting styles were
      predictive of lower self-reliance, whereas number of years lived in the United
      States was related to higher self-reliance. Those findings provide partial
      support for generalizing D. Baumrind's (1971) model of parenting styles to Korean
      American families, and the findings demonstrate the importance of considering
      acculturation issues in parenting studies.

PMID- 14719781
TI  - Nerve conduction in children suffering insulin dependent diabetes mellitus.
AB  - OBJECTIVE: To determine the incidence of peripheral neuropathy in children
      suffering Insulin Dependent Diabetes Mellitus (IDDM) as well as to determine the
      relationship between other criteria of the disease and neuropathy. METHODS: 40
      children (17 males, mean age 11.9 years) suffering IDDM and receiving insulin
      therapy involving two injections a day and 30 healthy children (17 males, mean
      age 11.7 years) were included in the study. They were inquired about their
      demographical characteristics as well as the presence of neurological symptoms.
      Their detailed neurological examinations were conducted. Their glycemic control
      values (Hb A1C) were recorded, and their nerve conduction studies were performed
      from right upper and lower extremities. RESULTS: All nerve conduction values of
      children with IDDM were found to be significantly lower (p<0.0001) as compared to
      the control group. 60% of diabetic children (n=24) were found to suffer
      peripheral neuropathy. Statistically significant relationships were found between
      the glycemic control values and the peroneal, sural, tibial, ulnar and median
      nerve conduction velocities, and also between the duration of disease and the
      peroneal, sural, tibial and median nerve conduction velocities. CONCLUSION: The
      peripheral neuropathy is rather a frequently observed complication in diabetic
      children. The duration of disease and impaired glycemic control play an important
      role in the development of neuropathy. The introduction of new methods designed
      to ensure better glycemic control will reduce the incidence of the complication.

PMID- 14719782
TI  - Iron supplementation in children with celiac disease.
AB  - OBJECTIVE: To evaluate the effect of iron supplementation, in addition to gluten
      free diet (GFD), on hematological profile of children with Celiac Disease (CD).
      METHODS: Children diagnosed as CD as per modified ESPGAN criteria were
      prospectively evaluated for their hematological profile at the time of their
      enrolment and after consuming GFD for at least one year. The results were
      compared with age and sex matched controls. Evaluation of hematological profile
      included hemoglobin estimation, complete blood counts, peripheral blood smear
      examination, serum iron, total iron binding capacity (TIBC), and serum ferritin
      estimation. All the enrolled cases were given iron supplementation in addition to
      exclusion of gluten from their diet. Repeat intestinal biopsy was performed in
      all the cases after completing 1 year on GFD. RESULTS: Twenty one children (mean
      age 6.67 years, range 4-11 years) diagnosed as CD who completed at least one year
      of regular follow up on GFD (mean 1.5 years, range 1-2 years) were analysed for
      their hematological profile at the time of enrolment and after consuming GFD and
      iron supplementation. At the time of enrolment all the children had hemoglobin
      level <11 gm%, 78% had microcytic hypochromic anemia and 22% had dimorphic
      anemia, with lower mean MCV, MCH and serum ferritin levels, and a significantly
      higher mean TIBC as compared to controls (p<0.001). In the follow up evaluation
      of these cases on GFD, mean hemoglobin levels were comparable with controls but
      the cases continued to have lower mean MCV, MCH serum ferritin levels (p<0.05)
      and higher mean TIBC (p<0.05). Seven children had mild anemia. Serum ferritin
      levels showed a negative correlation with the grade of villous atrophy and lamina
      propria infiltrate. CONCLUSION: Our results suggest that iron deficiency anemia
      (IDA) is commonly associated with CD and iron deficiency state continues for a
      longer time even after excluding gluten from the diet and iron supplementation.
      Apart from offering them GFD rich in iron, early detection and treatment of IDA
      and prophylactic iron folic acid supplementation will go a long way to optimize
      their mental and psychomotor functions.

PMID- 14719783
TI  - Birth-related fractures of long bones.
AB  - OBJECTIVE: Birth-related fractures of the long bones are not rare. METHODS: This
      study presents a retrospective analysis of birth-related fractures of long bones
      seen at the King Fahd Hospital of the University, Al-Khobar, Saudi Arabia.
      RESULTS: There were 21 fractures (clavicle 11, femur 6, humerus 3 and radius 1)
      during the 10-year period, with an overall incidence of 0.67 per 1000 live
      births. Neonates with fractures had higher birth-weight (p<0.001) as compared to
      the control group and other parameters like gestational age and mode of delivery
      were not significant. CONCLUSION: It is recommended that neonates with fractures
      must have quicker appointments in the outpatient clinics to prevent deformities
      and secondly those with fracture clavicles should be thoroughly evaluated to rule
      out damage to brachial plexas as well.

PMID- 14719784
TI  - Necrotizing fasciitis with chickenpox.
AB  - Necrotizing fasciitis can be observed in a wide variety of clinical settings in
      the pediatric age group. But necrotizing fasciitis as a complication of
      chickenpox is rare. Five cases of necrotizing fasciitis following chickenpox were
      treated in the authors' institutions. Clinical signs like fever, tachycardia,
      pallor, erythema, marked edema of the affected area and patchy areas of
      discoloration or gangrene of the skin were present and were the important clues
      to the seriousness of infection. Patients were treated with aggressive surgical
      debridement, frequent dressings, broad-spectrum antibiotics, nutritional support,
      and split skin grafting. Early diagnosis and aggressive surgical therapy are
      critical. Literature search showed necrotizing fasciitis following chickenpox has
      not been reported in India. We feel early suspicion and aggressive management can
      decrease the morbidity and mortality in this rare complication.

PMID- 14719785
TI  - Plasma cortisol levels in acute asthma.
AB  - OBJECTIVE: The study was undertaken with the aim to determine correlation between
      the initial plasma cortisol level and severity of asthma attack and the response
      to standard treatment for acute exacerbation of bronchial asthma in pediatric age
      group. METHODS: The study was performed in 33 asthmatic patients between 5-12
      years of age, presenting to pediatric emergency with acute exacerbation of
      bronchial asthma. None of the patients included in the present study was on
      steroids. Venous blood sample for determination of plasma cortisol level was
      taken and patients were nebulized with salbutamol every 20 minutes, up to 1 hour.
      The patients who failed to respond even after three nebulizations were labeled as
      nonresponders and repeat venous blood sample for plasma cortisol estimation was
      taken before giving injection hydrocortisone. In responders sample was taken 1
      hour after last nebulization. RESULTS: The mean plasma cortisol value at the time
      of admission in responders (12.42 +/- 1.9 microg/dl) was not found to be
      significantly different from that in nonresponders (13.1 +/- 2.74 microg/dl).
      Children with severe attack of asthma had significantly higher plasma cortisol
      levels both at the time of admission (p=0.03) and at the end of study (p=0.001),
      as compared to patients with moderate attack. The mean percentage change in
      plasma cortisol levels in nonresponders was an increase of 80.65 +/- 60.64%,
      whereas, in responders it decreased by 16.49 +/- 21.7% and this difference was
      statistically significant (p<0.05). CONCLUSION: The hypothalamo pituitary adrenal
      axis functions normally in asthmatic patients, producing a rise in cortisol
      levels corresponding to degree of stress; and from initial cortisol level alone,
      it cannot be predicted, whether a patient will respond to beta-2 agonist
      (salbutamol) nebulization alone or will require exogenous corticosteroids.

PMID- 14719786
TI  - Choosing a volume expander in critical care medicine.
AB  - The debate concerning the choice of crystalloids or colloids for resuscitation of
      the critically ill child is still unsettled. Moreover, the use of albumin in
      critically ill patients has been increasingly questioned because of the lack of
      clear-cut advantages over crystalloids as well as the concern for cost and the
      very minor risk of infection. Despite several meta-analyses addressing these
      issues, there is no data that supports the use of albumin unequivocally in any
      specific disease states. The suggestion that the use of albumin increases
      mortality in critically ill patients is not supported by data. There may be niche
      areas such as hypoalbuminic states, cirrhosis and burns where albumin may have
      distinct benefits. Alternatively synthetic colloids may be useful, however,
      concerns about coagulation problems and organ dysfunction persists.

PMID- 14719787
TI  - Prevention and control of HIV/AIDS.
AB  - HIV/AIDS in children has emerged during third phase of HIV epidemic as a result
      of high level of infection in women of child bearing age. Now it is being
      detected at an alarming rate. Various methods of HIV/AIDS transmission,
      prevalence of HIV in multitransfused, modes of prevention and control of HIV
      infection in children, antenatal care of HIV positive women, infant feeding
      options, safe blood along with other intervention have been reviewed.

PMID- 14719788
TI  - Platelet function disorders.
AB  - Platelet function disorders are a rare cause of bleeding in hematological
      practice. The inherited variety includes defects in platelet adhesion,
      aggregation, secretion and platelet procoagulant activities. The clinical
      presentation is usually mild with mainly mucocutaneous bleeds. Milder phenotypes
      may pass off unrecognized in childhood and present later in life. Testing
      includes a coagulation screen, which may show a prolonged bleeding time, followed
      by platelet aggregation tests with agonists. Flow cytometry for platelet surface
      markers, membrane glycoprotein analysis and facilities for identification of the
      genetic defect are usually available in research laboratories. Recent advances
      have opened vistas for antenatal testing. Bone marrow transplantation is the only
      curative therapeutic option available.

PMID- 14719789
TI  - Cord blood stem cell banking and transplantation.
AB  - Stem cells have the ability to divide for indefinite periods in culture and to
      give rise to specialized cells. Cord blood as a source of hematopoietic stem
      cells (HSC) has several advantages as it is easily available, involves non
      invasive collection procedure and is better tolerated across the HLA barrier.
      Since the first cord blood transplant in 1988, over 2500 cord blood HSC
      transplants have been done world wide. Since then, the advantages of cord blood
      as a source of hematopietic stem cells for transplantation have become clear.
      Firstly, the proliferative capacity of HSC in cord blood is superior to that of
      cells in bone marrow or blood from adults. A 100 ml unit of cord blood contains
      1/10th the number of nucleated cells and progenitor cells (CD34+ cells) present
      in 1000 ml of bone marrow, but because they proliferate rapidly, the stem cell in
      a single unit of cord blood can reconstitute the entire haematopoietic system.
      Secondly, the use of cord blood reduces the risk of graft vs host disease. Cord
      Blood Stem Cell banks have been established in Europe and United States to supply
      HSC for related and unrelated donors. Currently, more than 65,000 units are
      available and more than 2500 patients have received transplants of cord blood.
      Results in children have clearly shown that the number of nucleated cells in the
      infused cord blood influences the speed of recovery of neutrophils and platelets
      after myeloablative chemotherapy. The optimal dose is about 2 x 10(7) nucleated
      cells/kg of body weight. The present study was carried out for collection,
      separation, enumeration and cryopreservation of cord blood HSC and establishing a
      Cord Blood HSC Bank. 172 samples of cord blood HSC were collected after delivery
      of infant prior to expulsion of placenta. The average cord blood volume collected
      was 101.20 ml. Mononuclear cell count ranged from 7.36 to 25.6 x 10(7)/ml.
      Viability count of mononuclear cells was 98.1%. After 1 year of cryopreservation,
      the viability count on revival was over 82.1%. Related cord blood stem cell
      transplantation was carried out in three cases at Army Hospital (R&R), Delhi
      Cantt.

PMID- 14719790
TI  - Thrombocytopenic purpura as a presenting manifestation of tubercular
      lymphadenitis.
AB  - A 11-year-old girl presented with thrombocytopenic purpura along with cervical
      lymphadenopathy. There was no hepatosplenomegaly; no evidence of microangiopathy;
      bone marrow examination was normal. Acid fast bacilli were seen in fine needle
      aspiration cytology of the lymph node. A diagnosis of tubercular lymphadenitis in
      association with immune thrombocytopenia was made, and the platelet count
      recovered with antitubercular therapy. This report illustrates immune
      thrombocytopenia as a rare manifestation of childhood tuberculosis; the authors
      also discuss other causes of thrombocytopenia in childhood tuberculosis.

PMID- 14719791
TI  - Hyponatraemia and hypovolemic shock with tuberculous meningitis.
AB  - A 12-year-old boy with tuberculous meningitis and hydrocephalous, after
      undergoing revision of ventriculo-peritoneal shunt had persistent impairment of
      sensorium and episodes of hyponatremia (serum sodium 104 to 125 mmol/l),
      accompanied by polyuria, signs of poor peripheral, perfusion hypotension and low
      CVP, and high urinary sodium excretion (114-60 mmol/l). A diagnosis of cerebral
      salt wasting syndrome (CSWS) was made and was treated with saline replacement and
      fludrocortisone (10 microg/kg/day). Within next 3 days the sensorium, signs of
      shock, urine output and serum and urinary sodium returned to normal. The case
      illustrates that life-threatening hyponatremia in a child with neurological
      illness could be caused by CSWS, which must be differentiated from Syndrome of
      inappropriate antidiuretic hormone secretion (SIADH), as CSWS requires rigorous
      salt and volume replacement in contrast to fluid restriction in SIADH.

PMID- 14719792
TI  - Type 2 cryoglobulinemia treated with plasmapheresis associated with IgA
      nephropathy.
AB  - Cryoglobulinemia is caused by antibodies which precipitate in blood on exposure
      to cold, and redissolve on warming. The authors present a child with essential,
      Type 2 cryoglobulinaemia, successfully treated with plasmapheresis, who developed
      glomerulonephritis due to IgA nephropathy. Conservative treatment resulted in
      spontaneous improvement with no deterioration in renal function.

PMID- 14719793
TI  - Coffin-Lowry syndrome.
AB  - The Coffin-Lowry syndrome is an established syndrome of severe mental and growth
      retardation, characteristic dysmorphic features and skeletal anomalies. The
      authors report a one and half year old boy with classical features of this
      syndrome. Early recognition of this condition is important for genetic counseling
      and prevention of progressive skeletal deformities.

PMID- 14719794
TI  - Budd-Chiari syndrome due to antithrombin III deficiency.
AB  - Budd-Chiari syndrome is a disease complex with varied etiology and is one of the
      causes of post-hepatic portal hypertension. We report a 2 year-old boy who
      presented with Budd-Chiari syndrome due to congenital antithrombin III
      deficiency, who was managed with an expandable metal stent placed in the inferior
      vena cava and oral anticoagulation.

PMID- 14719795
TI  - Fetus-in-fetu.

PMID- 14719796
TI  - Metabolic stability, receptor binding, cAMP generation, insulin secretion and
      antihyperglycaemic activity of novel N-terminal Glu9-substituted analogues of
      glucagon-like peptide-1.
AB  - Glucagon-like peptide-1(7-36)amide (GLP-1) is an incretin hormone with
      therapeutic potential for type 2 diabetes. Rapid removal of the N-terminal
      dipeptide, His7-Ala8, by the ubiquitous enzyme dipeptidyl peptidase IV (DPP IV)
      curtails the biological activity of GLP-1. Chemical modifications or
      substitutions of GLP-1 at His7 or Ala8 improve resistance to DPP-IV action, but
      this often reduces potency. Little attention has focused on the metabolic
      stability and functional activity of GLP-1 analogues with amino acid substitution
      at Glu9, adjacent to the DPP IV cleavage site. We generated three novel Glu9
      substituted GLP-1 analogues, (Pro9)GLP-1, (Phe9)GLP-1 and (Tyr9)GLP-1 and show
      for the first time that Glu9 of GLP-1 is important in DPP IV degradation, since
      replacing this amino acid, particularly with proline, substantially reduced
      susceptibility to degradation. All three novel GLP-1 analogues showed similar or
      slightly enhanced insulinotropic activity compared with native GLP-1 despite a
      moderate 4-10-fold reduction in receptor binding and cAMP generation. In
      addition, (Pro9)GLP-1 showed significant ability to moderate the plasma glucose
      excursion and increase circulating insulin concentrations in severely insulin
      resistant obese diabetic (ob/ob) mice. These observations indicate the importance
      of Glu9 for the biological activity of GLP-1 and susceptibility to DPP IV
      mediated degradation.

PMID- 14719797
TI  - Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A
      structural and mechanistic comparison between the recombinant human and the
      purified porcine enzyme.
AB  - Dipeptidyl peptidase IV/CD26 (DP IV) is a multifunctional serine protease
      cleaving off dipeptides from the N-terminus of peptides. The enzyme is expressed
      on the surface of epithelial and endothelial cells as a type II transmembrane
      protein. However, a soluble form of DP IV is also present in body fluids. Large
      scale expression of soluble human recombinant His(6)-37-766 DP IV, using the
      methylotrophic yeast Pichia pastoris, yielded 1.7 mg DP IV protein per litre of
      fermentation supernatant. The characterisation of recombinant DP IV confirmed
      proper folding and glycosylation similar to DP IV purified from porcine kidney.
      Kinetic comparison of both proteins using short synthetic substrates and
      inhibitors revealed similar characteristics. However, interaction analysis of
      both proteins with the gastrointestinal hormone GLP-1(7-36) resulted in
      significantly different binding constants for the human and the porcine enzyme
      (Kd = 153.0 +/- 17.0 microM and Kd = 33.4 +/- 2.2 microM, respectively). In
      contrast, the enzyme adenosine deaminase binds stronger to human than to porcine
      DP IV (Kd = 2.15 +/- 0.18 nM and Kd = 7.38 +/- 0.54 nM, respectively). Even
      though the sequence of porcine DP IV, amplified by RT-PCR, revealed 88% identity
      between both enzymes, the species-specific variations between amino acids 328 to
      341 are likely to be responsible for the differences in ADA-binding.

PMID- 14719798
TI  - Effects of iron limitation on the respiratory chain and the membrane cytochrome
      pattern of the Euryarchaeon Halobacterium salinarum.
AB  - The effects of iron limitation on the electron transport chain of the extremely
      halophilic Euryarchaeon Halobacterium salinarum were analyzed. When iron was
      growth-limiting, the respiratory rates as well as the inhibition pattern of the
      membranes were significantly different from membranes of iron replete cells.
      Changes in the availability of iron cause the formation of different respiratory
      pathways including different entry sites for electrons, different terminal
      oxidases of the respiratory chain, and drastic changes of the cytochrome
      composition and of the relative amounts of cytochromes. Under iron-limiting
      conditions, mainly low-potential cytochromes were measured. EPR spectroscopic
      studies revealed that the amount of proteins containing iron-sulfur clusters is
      reduced in membranes under iron-limiting growth conditions. Taken together, our
      results strongly suggest for the first time an important role of iron supply for
      the bioenergetics of an Archaeon.

PMID- 14719799
TI  - Anti-mouse GPI-PLD antisera highlight structural differences between murine and
      bovine GPI-PLDs.
AB  - Despite its well characterised biochemistry, the physiological role of
      glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is unknown. Most
      of the previous studies investigating the distribution of GPI-PLD have focused on
      the human and bovine forms of the enzyme. Studies on mouse GPI-PLD are rare,
      partly due to the lack of a specific anti-mouse GPI-PLD antibody, but also due to
      the apparent low reactivity of existing antibodies to rodent GPI-PLDs. Here we
      describe the isolation of a mouse liver cDNA, the construction and expression of
      a recombinant enzyme and the generation of an affinity-purified rabbit anti-mouse
      GPI-PLD antiserum. The antibody shows good reactivity to partially purified
      murine and purified bovine GPI-PLD. In contrast, a rat anti-bovine GPI-PLD
      antibody shows no reactivity with the mouse enzyme and the two antibodies
      recognise different proteolytic fragments of the bovine enzyme. Comparison
      between the rodent, bovine and human enzymes indicates that small changes in the
      amino acid sequence of a short peptide in the mouse and bovine GPI-PLDs may
      contribute to the different reactivities of the two antisera. We discuss the
      implications of these results and stress the importance of antibody selection
      while investigating GPI-PLD in the mouse.

PMID- 14719800
TI  - Substrate specificity of glutaminyl cyclases from plants and animals.
AB  - Glutaminyl cyclases (QC) catalyze the intramolecular cyclization of N-terminal
      glutamine residues of peptides and proteins. For a comparison of the substrate
      specificity of human and papaya QC enzymes, a novel continuous assay was
      established by adapting an existing discontinuous method. Specificity constants
      (kcat/Km) of dipeptides and dipeptide surrogates were higher for plant QC,
      whereas the selectivity for oligopeptides was similar for both enzymes. However,
      only the specificity constants of mammalian QC were dependent on size and
      composition of the substrates. Specificity constants of both enzymes were equally
      pH-dependent in the acidic pH-region, revealing a pKa value identical to the pKa
      of the substrate, suggesting similarities in the substrate conversion mode.
      Accordingly, both QCs converted the L-beta homoglutaminyl residue in the peptide
      H-beta homoGln-Phe-Lys-Arg-Leu-Ala-NH2 and the glutaminyl residues of the
      branched peptide H-Gln-Lys(Gln)-Arg-Leu-Ala-NH2 as well as the partially cyclized
      peptide H-Gln-cyclo(N epsilon-Lys-Arg-Pro-Ala-Gly-Phe). In contrast, only QC from
      C. papaya was able to cyclize a methylated glutamine residue, while this compound
      did not even inhibit human QC-catalysis, suggesting distinct substrate
      recognition pattern. The conversion of the potential physiological substrates
      [Gln1]-gastrin, [Gln1]-neurotensin and [Gln1]-fertilization promoting peptide
      indicates that human QC may play a key role in posttranslational modification of
      most if not all pGlu-containing hormones.

PMID- 14719801
TI  - The binding of haptoglobin to apolipoprotein AI: influence of hemoglobin and
      concanavalin A.
AB  - Haptoglobin (Hp) can be purified by affinity chromatography using hemoglobin (Hb)
      linked Sepharose. Elution with 8 M urea is generally performed, resulting in
      heavy contamination of the Hp preparation by apolipoprotein AI (ApoAI), and
      partial loss of Hb binding activity. Hp, separated from ApoAI, was recovered by
      elution with glycine-HCl at pH 3. Complexes of the isolated protein with Hb or
      ApoAI were detected by enzyme-linked immunosorbent assay (ELISA). Competition
      between the two ligands in their interaction with Hp was observed. Concanavalin A
      (ConA), which binds the Hp carbohydrate chains, did not influence Hp binding to
      ApoAI. These results suggest that changes in the plasma levels of ApoAI or Hb
      affect the Hp role in regulating the reverse transport of cholesterol or
      preventing Hb-dependent oxidative damage.

PMID- 14719802
TI  - A novel water-soluble and cell-permeable calpain inhibitor protects myocardial
      and mitochondrial function in postischemic reperfusion.
AB  - The effects of the novel calpain inhibitor A-705239 were studied in isolated
      perfused rabbit hearts subjected to 45 min of global ischemia, followed by 60 min
      of reperfusion. During 15 min of perfusion the inhibitor accumulated in
      myocardial tissue up to 16 times the concentration in the perfusate. Almost
      complete recovery and survival of heart function (90%) was seen with an inhibitor
      concentration of 10(-8) M in the perfusion fluid when the compound was
      administered prior to ischemia. Left ventricular pressure amplitude and coronary
      flow showed significantly higher values during reperfusion in the presence of the
      inhibitor. A-705239 significantly reduced the release of creatine kinase, from
      166+/-49 U/l in untreated hearts to 44+/-10 U/l, and diminished the release of
      lactate dehydrogenase from 118+/-20 U/l in untreated hearts to 63+/-4 U/l.
      Mitochondrial dysfunction following ischemia and reperfusion was markedly
      attenuated by the inhibitor. Thus, the state 3 respiration rate only decreased to
      4.2 in contrast to 2.6 nmol O2/(min x mg s.w.) in untreated hearts, reflecting a
      reduced damage of oxidative phosphorylation. Furthermore, in the presence of the
      inhibitor the inner mitochondrial membranes became less permeable as indicated by
      a smaller leak respiration. The excellent properties of A-705239 should make this
      compound a valuable tool for further pharmacological studies.

PMID- 14719803
TI  - Potent bivalent inhibition of human tryptase-beta by a synthetic inhibitor.
AB  - Human tryptase-beta (HTbeta) is a unique serine protease exhibiting a frame-like
      tetramer structure with four active sites directed toward a central pore. Potent
      inhibition of HTbeta has been attained using CRA-2059. This compound has two
      phenylguanidinium head groups connected via a linker capable of spanning between
      two active sites. The properties of the CRA-2059:HTbeta interaction were defined
      in this study. Tight-binding reversible inhibition was observed with an
      inhibition constant (Ki) of 620 pM, an association rate constant of 7x10(7) M(-1)
      s(-1) and a relatively slow dissociation rate constant of 0.04 s(-1). Bivalent
      inhibition was demonstrated by displacement of p-aminobenzamidine from the
      primary specificity pocket with a stoichiometry, [CRA-2059]0/[HTbeta]0, of 0.5.
      The potency of the bivalent interaction was illustrated by CRA-2059 inhibition of
      HTbeta, 24% or 53% inhibited by pre-incubation with an irreversible inhibitor.
      Two interactions were observed consistent with mono- and bi-valent binding; the
      Ki value for bivalent inhibition was at least 10(4)-fold lower than that for
      monovalent inhibition. Comparison of the affinities of CRA-2059 and
      phenylguanidine for HTbeta finds an approximate doubling of the free energy
      change upon bivalent binding. This doubling suggests that the linker portion
      minimally hinders the binding of CRA-2059 to HTbeta. The potency of CRA-2059 is
      thus attributable to effective bivalent binding.

PMID- 14719804
TI  - Aza-peptide epoxides: potent and selective inhibitors of Schistosoma mansoni and
      pig kidney legumains (asparaginyl endopeptidases).
AB  - Aza-peptide epoxides are a new class of irreversible cysteine protease
      inhibitors. Derivatives containing a P1 aza-asparagine residue are specific for
      Schistosoma mansoni and pig kidney legumains, which are clan CD cysteine
      proteases. The inhibitors have second-order rate constants of up to 10(4) M(-1)
      s(-1) with pig kidney legumain and IC50 values as low as 45 nM with S. mansoni
      legumain. The most potent epoxides contain an ester moiety with S,S
      stereochemistry attached to the epoxide. Interestingly, amide and amino acid
      derivatives of the epoxysuccinate moiety were not inhibitors of legumain, while
      disubstituted amide derivatives are quite potent. The inhibitors have little or
      no inhibitory activity with other proteases such as caspases, chymotrypsin,
      papain, cathepsin B, granzyme B, and various aspartyl proteases.

PMID- 14719805
TI  - Semisynthesis and application of carboxyfluorescein-labelled biologically active
      human interleukin-8.
AB  - Human interleukin 8 (hIL-8), a neutrophil-activating and chemotactic cytokine, is
      known to play an important role in the pathogenesis of a large number of
      neutrophil-driven inflammatory diseases. This cytokine belongs to the family of
      CXC chemokines, mediating the response through binding to the seven-transmembrane
      helical G protein-coupled receptors CXCR1 and CXCR2. For the first time, we
      employed the expressed protein ligation (EPL) strategy to chemokine synthesis and
      subsequent modification. The ligation site was chosen with respect to the
      position of four cysteine residues within the hIL-8 sequence. Ligation with
      synthetic peptides that carry cysteine at their N-termini resulted in full-length
      hIL-8 and the specifically carboxyfluorescein-labelled analogue [K69(CF)]hIL-8(1
      77). [K69(CF)]hIL-8(1-77) was fully active as shown by inhibition of cAMP
      production. Furthermore, this analogue was used to study receptor internalisation
      in human promyelotic HL60 cells that express CXCR1 and CXCR2 receptors. Binding
      and quenching studies were performed on HL60 membranes and suggest that the C
      terminus of IL-8 is accessible to solvent in the receptor-bound state. Thus, we
      introduce here a powerful approach that allows the site-specific incorporation of
      chemical modifications into the sequence of chemokines, which opens new avenues
      for studying IL-8 function.

PMID- 14719806
TI  - Asymmetric thiosulfinations catalyzed by bovine serum albumin and horseradish
      peroxidase.
AB  - Bovine serum albumin (BSA) and horseradish peroxidase (HRP) catalyzed the
      monooxidation of organic disulfides with peroxides to optically active
      thiosulfinates. With BSA, a hydrophobic disulfide was oxidized in a
      stereoselective manner, and the nature of the oxidant (H2O2 or tert-butyl
      hydroperoxide) controlled the absolute configuration of the product. The rates of
      HRP-catalyzed thiosulfination in methanol were several times faster than in water
      but the enzyme was less stereoselective.

PMID- 14719807
TI  - Extracellular matrix substrata alter adipocyte yield and lipogenesis in primary
      cultures of stromal-vascular cells from human adipose.
AB  - The stromal-vascular fraction of human adipose was subjected to in vitro
      adipogenesis on different extracellular matrix substrata. Adipose tissue was
      harvested from the breast of 25 to 45 year-old female patients undergoing
      elective surgery. After 24 d, less than 5% of stromal-vascular cells had
      converted to adipocytes on fibronectin, 13% to 28% on tissue culture plastic and
      collagen I; and 59% +/- 7% on Matrigel. Lipid volume surpassed 4.5 x 10(3)
      microm3 cell(-1) for Matrigel and was 30% lower for the other substrata. Cell
      proliferation was evident for Matrigel and fibronectin, and cell spreading was
      most pronounced for fibronectin with a projected area exceeding 3 x 10(3) microm2
      cell(-1). These results are relevant to the design of an adipose implant,
      providing insight into its feasibility and scaffold composition.

PMID- 14719808
TI  - Expression and characterization of recombinant NH2-terminal cell binding fragment
      of vitronectin in E. coli.
AB  - A recombinant peptide fragment of vitronectin (rVN143), that includes the Arg-Gly
      Asp (RGD) cell recognition site, was expressed in Escherichia coli using a
      prokaryotic expression system. The addition of recombinant rVN143 peptide
      enhances cell adhesion and proliferation similar (approximately 70%) to those of
      native VN.

PMID- 14719809
TI  - Immobilization of Pseudomonas delafieldii with magnetic polyvinyl alcohol beads
      and its application in biodesulfurization.
AB  - Pseudomonas delafieldii was immobilized in magnetic polyvinyl alcohol (PVA) beads
      using a hydrophilic magnetic fluid, which was prepared by a co-precipitation
      method. The beads had distinct super-paramagnetic properties and were compared
      with immobilized cells in non-magnetic PVA beads. Their desulfurizing activity
      was increased slightly from 8.7 to 9 mmol sulfur kg(-1) (dry cell) h(-1). The
      main advantages was that the magnetic immobilized cells maintain a high
      desulfurization activity and remain in good shape after 7 times of repeated use,
      while the non-magnetic immobilized cells could only be used for 5 times.
      Furthermore, the magnetic immobilized cells could be easily collected or
      separated magnetically from the biodesulfurization reactor.

PMID- 14719810
TI  - Rhizopus arrhizus--a producer for simultaneous saccharification and fermentation
      of starch waste materials to L(+)-lactic acid.
AB  - Rhizopus arrhizus, strain DAR 36017, produced L(+)-lactic acid in a simultaneous
      saccharification and fermentation process using starch waste effluents. Lactic
      acid at 19.5-44.3 g l(-1) with a yield of 0.85-0.96 g g(-1) was produced in 40 h
      using 20-60 g starch l(-1). Supplementation of nitrogen source may be unnecessary
      if potato or corn starch waste effluent was used as a production medium.

PMID- 14719811
TI  - Over-expression of recombinant human interferon-gamma in high cell density
      fermentation of Escherichia coli.
AB  - Human interferon-gamma (hIFN-gamma) was expressed in Escherichia coli BL21(DE3)
      under the control of the T7 promoter. Glucose was used as the sole source of
      carbon and energy with simple exponential feeding rate in fed-batch process. Cell
      density of recombinant E. coli was reached to 100 g dry wt l(-1) under both
      constant (0.12 h(-1)) and variable (0.12-0.52 h(-1)) specific growth rates. In
      the variable specific growth rate fed-batch process, plasmid stability and
      specific yield of rhIFN-gamma were greater than constant specific growth rate fed
      batch process. The final specific yield and overall productivity of rhIFN-gamma
      were 0.35 +/- 0.02 g rhIFN-gamma g(-1) dry cell wt and 0.9 +/- 0.05 g rhIFN-gamma
      l(-1) h(-1) in the variable specific growth rate fed-batch process, respectively.

PMID- 14719812
TI  - Enzymatic synthesis and antioxidant property of gelatin-catechin conjugates.
AB  - Gelatin-catechin conjugate was synthesized by the laccase-catalyzed oxidation of
      catechin in the presence of gelatin. The conjugate had a good scavenging activity
      against superoxide anion radicals. Moreover, the conjugate showed an amplified
      inhibition effect on human low density lipoprotein oxidation initiated by 2,2'
      azobis(2-amidinopropane)dihydrochloride as a radical generator.

PMID- 14719813
TI  - Development of a set of expression vectors in Hansenula polymorpha.
AB  - Four expression vectors based on formate dehydrogenase promoter (FMDp) and
      methanol oxidase promoter (MOXp) from Hansenula polymorpha were developed to
      express heterologous genes in Hansenula polymorpha. A secretion signal sequence
      of the mating factor-alpha from Saccharomyces cerevisiae was inserted in the
      secretory expression plasmids for efficient secretion. A modified green
      fluorescent protein (mGFP5) was used as the marker of expression for the first
      time in H. polymorpha NCYC495 (leu 1.1) to determine the expression ability of
      these plasmids. The mGFP5 thus expressed retained its biochemical and
      physiological properties, such as accumulation inside cells and efficient
      secretion into the culture media. These results indicated that the four
      integrative vectors are useful expression systems which could be directly applied
      for production of heterologous proteins of interests in H. polymorpha.

PMID- 14719814
TI  - Fibronectin fragment promotes osteoblast-associated gene expression and
      biological activity of human osteoblast-like cell.
AB  - A fibronectin fragment, which spans from the ninth to tenth type III domain,
      showed > 95% biological activity in promoting osteoblast adhesion, proliferation
      and differentiation level compared with those of native fibronectin (FN)
      molecule. This suggests that the FN type III ninth-tenth domain fragment serves a
      good substitute for native FN in biomimetic application for osteogenesis.

PMID- 14719815
TI  - beta-Glucan production by Botryosphaeria rhodina on undiluted olive-mill
      wastewaters.
AB  - Botryosphaeria rhodina produced beta-glucan when grown on undiluted olive-mill
      wastewaters (OMW). The production of exopolysaccharide increased with the COD up
      to 17.2 g l(-1) on the most loaded OMW (151 and 66 g l(-1) of COD and total
      sugar, respectively). The total phenol content of OMW was reduced from 8 to 4.1 g
      l(-1).

PMID- 14719816
TI  - Cryopreservation of the unicellular marine alga, Nannochloropsis oculata.
AB  - In microalgal culture collections, as in many biological resource centres,
      cryoconservation is the most attractive method for the long-term, secure storage
      of living material. Nannochloropsis oculata, a marine unicellular alga, is of
      interest in the field of biotechnology due to its high lipid content. Of various
      cryoprotectants tested for their toxicity and for their ability to prevent
      cryoinjury, glycerol (final concentration 1.1 M) was the most efficient. When
      glycerol-treated cultures were submitted to a strictly regulated cooling rate (-3
      degrees C min(-1)), they attained the control culture density within 13 d after
      thawing.

PMID- 14719817
TI  - Focussed beam reflectance measurement (FBRM) monitoring of particle size and
      morphology in suspension cultures of Morinda citrifolia and Centaurea calcitrapa.
AB  - Laser light scattering technology, as applied in the Lasentec focussed beam
      reflectance measurement (FBRM) system, was used to characterise two
      morphologically dissimilar plant cell suspension cultures, Morinda citrifolia and
      Centaurea calcitrapa. Shake-flask suspensions were analysed in terms of biomass
      concentration and aggregate size/shape over the course of typical batch growth
      cycles. For the heavily aggregated C. calcitrapa, biomass levels [from 10-160 g
      fresh weight (fw) l(-1))] were linearly correlated with FBRM counts. For M.
      citrifolia, which grows in unbranched chains of 2-10 elongated cells, linear
      correlation of biomass concentration with FBRM counts was applicable in the range
      0-100 g fw l(-1); at higher levels (100-300 g fw l(-1)), biomass was non-linearly
      correlated with FBRM counts and length-weighted average FBRM chord length. For
      both cell systems, particle morphology (size/shape) was quantified using semi
      automated digital image analysis. The average aggregate equivalent diameter (C.
      calcitrapa) and average chain length (M. citrifolia), determined using image
      analysis, closely tracked the FBRM average chord length. The data clearly
      demonstrate the potential for applying the FBRM technique for rapid
      characterisation of plant cell suspension cultures.

PMID- 14719818
TI  - Production of transglutaminase from Bacillus circulans on solid-state and
      submerged cultivations.
AB  - A Bacillus circulans strain, isolated in the Amazon basin, produced a
      transglutaminase (EC 2.3 x 2.13) in both submerged and solid-state cultivation.
      Enzyme activity in the former case reached 0.69 U ml(-1) after 160 h cultivation
      on starch based medium, and in the latter 0.61 U ml(-1) after 60 h cultivation on
      soybean industrial fibrous residue, a non-expensive agro-industrial residue.

PMID- 14719819
TI  - Poly(L-lactide) degradation by Kibdelosporangium aridum.
AB  - A new poly(L-lactide) (PLA)-degrading actinomycete, Kibdelosporangium aridum,
      degraded more than 97 mg out of 100 mg added high molecular weight PLA film (Mn:
      3.4 x 10(5)) within 14 d in liquid culture. L-Lactic acid, the monomeric
      degradation product of PLA, was totally assimilated by the strain. In solid
      culture, many distinct grooves formed by the morphology of filamentous
      microorganisms on the surface of a PLA film were observed by scanning electron
      microscopy.

PMID- 14719820
TI  - Isolation and characterisation of resistant-to-fermentation carbohydrate polymers
      from cultures of Rhizopus nigricans grown on agrofood waste materials.
AB  - Rhizopus nigricans was cultivated in a liquid medium using lemon, mandarin,
      orange, pear and melon peel or artichoke bracts as the carbon source. In all
      cultures, a carbohydrate polymer fraction remained resistant to fermentation.
      These fractions were isolated in gram amounts and characterised. The molecular
      weight distribution of the fractions and its sugar composition resembles those of
      the hairy-regions of the pectins. In the fractions, four main carbohydrates were
      found: 4-7 mol% Rha, 42-59 mol% Ara, 7-14 mol% Gal, 17-33 mol% GalA.

PMID- 14719821
TI  - Growth and photosynthesis limitation of marine red tide alga Skeletonema costatum
      by low concentrations of Zn2+.
AB  - The specific growth rate, cell final yields and extracellar carbonic anhydrase
      activity of the red tide alga Skeletonema costatum increased with increasing
      concentrations of Zn2+ from 0 to 12 pM, but decreased when Zn2+ was over 24 pM.
      However, cells grown under high concentrations of Zn2+ had higher activities of
      intracellular carbonic anhydrase than those grown under low concentrations of
      Zn2+. Chlorophyll a-specific light-saturated photosynthetic rate (P(Chla)), dark
      respiration rate (R(chla)) and apparent photosynthetic efficiency (alpha(chla))
      significantly increased with increasing concentrations of Zn2+ from 0 to 3 pM,
      but decreased when increasing concentrations of Zn2+ from 3 to 66 pM.
      Photorespiration is the lowest when cells cultured in 3 pM Zn2+. The results
      suggest physiological activity of Skeletonema costatum is very sensitive to the
      prevailing concentration of Zn2+.

PMID- 14719822
TI  - Changes in gluconic acid, polyols and major volatile compounds in sherry wine
      during aging with submerged flor yeast cultures.
AB  - The traditional biological process by which sherry wines are aged can be
      accelerated by using submerged Saccharomyces cerevisiae var. capensis (G1) strain
      cultures previously grown in glycerol. The used controlled shaking conditions
      raise the acetaldehyde, acetoin, and meso 2,3-butanediol contents in the wine,
      and increases the consumption of gluconic acid by flor yeast relative to
      traditional biological aging under flor yeast velum.

PMID- 14719823
TI  - Treatment of winery effluent with upflow anaerobic sludge blanket (UASB)-
      granular sludges enriched with Enterobacter sakazakii.
AB  - Three upflow anaerobic sludge blankets (UASBs) were evaluated for the treatment
      of winery wastewater: the first was seeded with granular sludge enriched with
      Enterobacter sakazakii and reached a 90% COD removal within 17 d at hydraulic
      retention time of 24 h; the second was seeded with brewery granules and achieved
      85% COD removal within 50 d, the third was seeded with just sludge and showed the
      typical problems encountered with conventional sludge seeding and had
      continuously to be re-seeded. A PCR-based technique was developed for the rapid
      detection of E. sakazakii in the granular sludge.

PMID- 14719824
TI  - Comparison of methods for sample preparation of individual rat cerebrospinal
      fluid samples prior to two-dimensional polyacrylamide gel electrophoresis.
AB  - Different pre-treatment methods have been compared for two-dimensional mapping of
      individual rat cerebrospinal fluid samples based on acetone, trichloroacetic
      acid/acetone and methanol/acetone precipitation of proteins. Acetone
      precipitation following incubation with DTT gave the highest protein recovery
      (72%) and the largest number of protein spots (92 +/- 4) as well as minimizing
      the time taken.

PMID- 14719825
TI  - Salicylate biodegradation by various algal-bacterial consortia under
      photosynthetic oxygenation.
AB  - Four green microalgae (Chlorella sorokiniana, Chlorella vulgaris, Scenedesmus
      obliquus and Selenastrum capricornutum), a wild Bolivian microalga strain and two
      cyanobacteria (Anabaena catenula and Microcystis aeruginosa) were compared for
      tolerance to salicylate, O2 production capacity and ability to support salicylate
      degradation by a Ralstonia basilensis strain in symbiotic microcosms with the
      microalgae. Microcystis aeruginosa had the highest tolerance to salicylate at 500
      mg l(-1) and 1500 mg l(-1) but only produced 0.7 mg O2 l(-1) h(-1) in the absence
      of pollutant. Chlorella sorokiniana resisted salicylate at 1500 mg l(-1) with the
      highest O2 production in the absence of salicylate (26 mg l(-1) h(-1)) closely
      followed by the Bolivian microalga (23 mg l(-1) h(-1)) and Chlorella vulgaris (21
      mg l(-1) h(-1)). Selenastrum capricornutum and Anabaena catenula were completely
      inhibited by salicylate at 500 mg l(-1). When inoculated with Ralstonia sp. and
      supplied with salicylate, Chlorella sorokiniana had the highest removal rate (19
      mg l(-1) h(-1)), followed by the wild Bolivian strain (18 mg l(-1) h(-1)) and
      Chlorella vulgaris (14 mg l(-1) h(-1)).

PMID- 14719826
TI  - Construction of linear functional expression elements with DNA fragments created
      by site-specific DNA nickase, N.Bpu10 I, and exonuclease III.
AB  - A method to assemble linear expression elements for rapid gene expression is
      described. Primers containing target specific sequences and N.Bpu10 I nickase
      recognition sites were used to amplify promoter, open reading frame and
      terminator fragments. Amplified fragments were treated with N.Bpu10 I nickase and
      exonuclease III to generate overhangs for directional ligation. These fragments
      were ligated and further amplified with element-specific primers. The amplified
      DNA was transfected into mammalian cells for gene expression.

PMID- 14719827
TI  - Immunological comparison of native and recombinant egg allergen, ovalbumin,
      expressed in Escherichia coli.
AB  - Chicken ovalbumin is one of the major egg white allergens which causes IgE
      mediated food hypersensitivity. A gene encoding for chicken ovalbumin (Gad dI)
      was isolated from chicken oviduct by PCR amplification and was cloned under the
      control of T5 promoter fused with a six-histidine tag at the N-terminal end.
      Escherichia coli harbouring this construct expressed high quantities of the
      recombinant protein in the form of soluble fraction. The protein was purified
      using affinity chromatography on a Ni(2+)-nitrilotriacetic acid agarose column
      and was further purified to homogeneity by ion exchange chromatography.
      Homogeneity was confirmed through SDS-PAGE, Western blot and secondary
      conformation analysis. The reactivity of the recombinant and native protein was
      tested against six egg allergic human patient's sera and the IgE and IgG binding
      activity was tested using both Western blot and ELISA. When compared to native
      ovalbumin, the recombinant protein had similar binding activity in
      immunoblotting, but slightly increased activity by ELISA. Circular dichroism
      revealed that the recombinant protein had a slightly less compact structure than
      the native form. Both antigens exhibited a similar immunogenicity in mice.

PMID- 14719828
TI  - Aerobic biodegradation of trichloroethylene using a consortium of five bacterial
      strains.
AB  - Degradation with an aerobic consortium was used to evaluate the bioremediation
      trichloroethylene (TCE) as a model substrate. After one week, 228-1186 mg TCE l(
      1) was degraded at rates of 20-50 microg TCE l(-1) h(-1). The introduction of 10
      mg toluene l(-1) enhanced the degradation rates for TCE when greater than 600 mg
      l(-1). Using isolated enzymes, a TCE degradation intermediate(s) appears
      inhibitory to the oxygenase enzymes thereby diminishing the overall degradation.

PMID- 14719829
TI  - Cloning and expression of a putative cytochrome P450 gene that influences the
      colour of Phalaenopsis flowers.
AB  - Anthocyanins are responsible for reds through blues in flowers. Blue and violet
      flowers generally contain derivatives of delphinidin, whereas red and pink
      flowers contain derivatives of cyanidin or pelargonidin. Differences in
      hydroxylation patterns of these three major classes of anthocyanidins are
      controlled by the cytochrome P450 enzymes. Flavonoid-3',5'-hydroxylase, a member
      of the cytochrome P450 family, is the key enzyme in the synthesis of 3',5'
      hydroxylated anthocyanins, generally required for blue or purple flowers. Here we
      report on the isolation of a cDNA clone of a putative flavonoid-3',5'-hydroxylase
      gene from Phalaenopsis that was then cloned into a plant expression vector.
      Transient transformation was achieved by particle bombardment of Phalaenopsis
      petals. The transgenic petals changed from pink to magenta, indicating that the
      product of the putative flavonoid-3',5'-hydroxylase gene influences anthocyanin
      pigment synthesis.

PMID- 14719830
TI  - A simple protocol for isolation of fungal DNA.
AB  - Genomic DNA was isolated from as little as 2 mg dry biomass of Magnaporthe grisea
      by microwave treatment within 30 s. The quantity of DNA was good enough for PCR
      analysis and Dot blot hybridization. This technique can be used for various
      studies, such as DNA fingerprinting to study the population structure of the
      phytopathogen in different regions, and for a quick screening of M. grisea
      transformants.

PMID- 14719831
TI  - Monitoring the transport of recombinant Candida rugosa lipase by a green
      fluorescent protein-lipase fusion.
AB  - In a batch cultivation of Pichia pastoris expressing Candida rugosa lipase 1
      (CRL1), secretion of 200 microg lipase ml(-1) of culture was achieved in sorbitol
      based medium. However, a large amount of recombinant protein was retained
      intracellularly throughout the fermentation, pointing to the transport step as a
      major bottleneck. Therefore a translational fusion with the green fluorescent
      protein (GFP) was constructed that was expressed and transported similarly to the
      native lipase and retained catalytic activity. This analytical tool enables a
      rapid monitoring of product localization and amount, based on GFP-associated
      fluorescence.

PMID- 14719832
TI  - Protease expression in the supernatant of Chinese hamster ovary cells grown in
      serum-free culture.
AB  - The protease activity secreted by the Chinese Hamster Ovary (CHO-K1) cell line
      grown in serum-free medium was examined by substrate gel electrophoresis
      (zymography). The cell line expressed extracellular proteases that were active on
      gelatin zymograms but not on casein zymograms. The main protease band visible by
      gelatin zymography was approx. 92 kDa. Incubation of the conditioned medium with
      aminophenylmercuric acetate (APMA) resulted in the appearance of gelatinase
      activity at 82 kDa. Incubation of the conditioned media with EDTA significantly
      decreased the gelatinolytic activity of both the 92 kDa and 82 kDa forms,
      indicating the gelatinase responsible was a metalloprotease. Immunoblotting of
      the conditioned medium showed the gelatinase to be the pro- form of matrix
      metalloprotease-9 (pro-MMP-9), also known as gelatinase B.

PMID- 14719833
TI  - Calculation of fermentation parameters from the results of a batch test taking
      account of the volume of biomass in the fermenting medium.
AB  - The values of fermentation parameters calculated from the measured concentrations
      of substrates and/or products may be significantly affected by the volume of
      biomass in the fermenting medium. Corrections proposed in this paper should be
      evaluated and, depending on their magnitude, considered in order to obtain more
      representative results.

PMID- 14719834
TI  - Orthotics and insoles for the forefoot: the European way.
AB  - Technical aids in the treatment of foot problems have been known for hundreds of
      years. In the German-speaking countries, especially, shoemakers, prosthetists,
      and orthotists are well respected. They have great skills and provide the
      orthopedic surgeon with alternatives to surgery. Also, the combination of surgery
      and technical aids is important because suboptimal surgical results can be
      improved by a good orthopedic device.

PMID- 14719835
TI  - Iloprost for the treatment of bone marrow edema in the hindfoot.
AB  - The parenteral application of the vasoactive drug, iloprost, might be a viable
      option for the treatment of BMES of different origins, especially ischemic ones.
      In edema that is secondary to osteoarthrosis or stress, the effect of therapy
      with iloprost depends on the grade of the basic disease. The natural course of
      the disease, as well as the normalization of the signal pattern of the MRI, seem
      to be accelerated.

PMID- 14719836
TI  - Forefoot morphotype study and planning method for forefoot osteotomy.
AB  - In the reconstruction of the hip, knee, or any other joint, preoperative planning
      is necessary for avoiding mistakes during surgery. Since 1995, the authors have
      been doing this before forefoot surgery to increase the accuracy of the surgery.
      As much as possible, they try to correct only the lesion and to avoid preventive
      or extensive surgery on adjacent rays, except if the correction leads to a
      modified dysharmonious new morphotype with high risk of transfer lesion. The
      tolerance length seems to be 2 mm, particularly on the middle metatarsals (M2 and
      M3). This surgery should be performed only if the midfoot and backfoot are
      correct and if the gastrocnemius muscle has been checked on to eliminate a
      retraction needing stretching exercises before and generally after surgery.

PMID- 14719837
TI  - First metatarsophalangeal joint replacement: the method of choice for end-stage
      hallux rigidus?
AB  - Replacement of the first metatarsophalangeal (MTP) joint remains critical because
      of complex biomechanical conditions and implant fixation. After a 3-year follow
      up, most patients who experienced an MTP joint replacement were extremely
      satisfied with the outcome. Plantar pressure distribution revealed a marked
      improvement. Nevertheless, recovery of MTP dorsiflexion was limited and joint
      stability worsened. Radiologically, one-third of the prostheses showed
      radiolucent lines as a sign of implant loosening. MTP replacement offers distinct
      advantages in the treatment of end-stage hallux rigidus, but requires further
      research on implant design and osseous fixation.

PMID- 14719838
TI  - Medial ankle instability.
AB  - Medial instability is suspected on the basis of a patient's ankle feeling like it
      is "giving way," especially medially, when walking on uneven ground, downhill, or
      down stairs, pain at the anteromedial aspect of the ankle, and sometimes pain in
      the lateral ankle, especially during dorsiflexion of the foot. A history of a
      chronically unstable feeling that is manifested by recurrent injuries with pain,
      tenderness, and sometimes bruising over the medial and lateral ligaments, is
      considered to indicate combined medial and lateral instability that is believed
      to result in rotational instability of the talus in the ankle mortise. Pain on
      the medial gutter of the ankle and a valgus and pronation deformity of the foot
      are hallmarks of the disorder. The deformity typically can be corrected by the
      activation of the posterior tibial muscle. In contrast to stress radiographs,
      arthroscopy is a helpful diagnostic tool in verifying medial instability; it
      proved that the lateral ankle ligaments also can be involved. The treatment for
      symptomatic medial instability of the ankle might include reconstruction of all
      involved ligaments at the medial, and, if necessary, the lateral ankle. In the
      case of progressed foot deformity or bilateral long-standing valgus and pronation
      deformity of the foot, an additional calcaneal lengthening osteotomy might be
      considered. A classification of the instability into three types has been helpful
      for determining surgical treatment and the after treatment. This treatment
      concept provides high patient satisfaction and reliable clinical results.

PMID- 14719839
TI  - Cartilage repair of the talus.
AB  - The cause of a typical osteochondral lesion of the talus is traumatic; if
      symptomatic, several options exist. Because nonoperative treatment results in no
      more than 50% good to excellent results, the following types of surgery are in
      clinical use: (1) debridement and drilling, (2) osteochondral transfer, and (3)
      autologous chondrocyte transplantation. Reported good to excellent results are at
      least 80% in the short term. Currently available data allow no recommendation of
      a specific therapy for a specific lesion. Advocates of drilling and debridement
      accept that the repair tissue is fibrocartilage; osteochondral transfer includes
      a donor side morbidity. We are still at the beginning of cartilage repair; it
      will take time before a certain type of lesion can be treated with the best
      modality because that requires comparative randomized prospective studies with a
      long follow-up. All modern cartilage repair techniques, that were initially
      investigated at the knee joint, are now in use for ankle osteochondral lesions.
      Reported short-term success rates are greater than 80%. Further improvements will
      depend on the understanding of the pathogenesis and the role of contributing
      factors (eg, instability).

PMID- 14719840
TI  - Foot malignancies: a multidisciplinary approach.
AB  - Malignant osseous and soft tissue tumors of the foot are rare and should be
      considered in patients who have foot-related symptoms. Most sarcomas affect
      patients who are older than 55 years; however, many young patients who are
      otherwise healthy, may present with malignant foot and ankle lesions. In addition
      to benign and malignant neoplasms, pseudotumorous conditions mimic neoplastic
      lesions and should be differentiated before any treatment is undertaken.
      Invasiveness is a characteristic of sarcomas. The foot is a terminal anatomic
      structure, with closed and tight compartments and well-vascularized tissues, that
      predispose it to hematogenous and lymphatic metastases. Patients who have a
      malignant foot tumor should be referred to an orthopedic oncologist for further
      evaluation and treatment. The goals of treatment include local tumor control,
      restoration of function and stability during standing and walking, long-term
      survival, and improved quality of life. In most cases, wide surgical margins
      require a ray, Syme, midtarsal, or below-the-knee amputation. Recent advances in
      chemotherapy and radiotherapy have allowed limb salvage procedures with wide
      tumor resections. Because overall survival is greatly improved in these patients,
      the reconstruction of skeletal defects needs to be more functional and durable.
      After tumor resection, reconstruction of the skeletal and soft tissue defects is
      possible by using bone allografts or vascularized autografts, arthrodesis, and
      free vascularized musculocutaneous flaps.

PMID- 14719841
TI  - Maternal immunization.
AB  - Maternal immunization embraces the concepts that vaccines given to pregnant women
      enhance their resistance to vaccine-preventable diseases and passive antibodies
      that cross the placenta protect the neonate for the first 3 to 6 months of life.
      It is a great public health move to get excellent protection at a small cost.
      Because all recommended vaccines for use in pregnancy are safe, it makes good
      sense to bring patients up to date on vaccines.

PMID- 14719842
TI  - Developments in the screening for Chlamydia trachomatis: a review.
AB  - Many studies have evaluated selective screening criteria for women in various
      settings. Most have concluded and all guidelines recommend that all women aged <
      25 be screened yearly for C. trachomatis infection. Behavioral criteria, such as
      the number of sex partners, new or more than one sex partners, and previous
      infection, also can serve as criteria for screening women aged > 25. Because re
      infection rates are high and occur within a few months, complications may be
      reduced further if partners are treated and women rescreened 4 to 6 months after
      initial infection. Revised recommendations for C. trachomatis screening programs
      have stated that more frequent screening may be considered among women < 20 and
      those with recent infection. Screening in nontraditional settings and careful
      evaluation of local prevalence and risk factor information should be encouraged.
      Private providers and emergency room providers should discuss screening
      recommendations and adopt a C. trachomatis screening policy for the population
      they serve. The HEDIS measure should serve to encourage at least annual screening
      of 15- to 25-year-old sexually active females through providers linked to managed
      care organizations. In general, high yields (ie, percentage of tests that are
      positive) in nontraditional settings and enhanced feasibility and acceptability
      of urine-based tests may encourage further innovative approaches to reach and
      screen populations at risk. Several issues remain to be addressed to increase the
      effectiveness of screening efforts. If more sensitive amplification tests are
      used widely, more infected persons will be identified and treated, and
      transmission patterns may change, particularly if partner treatment also occurs.
      Current screening criteria should continue to be re-evaluated. An important issue
      that affects testing methods includes the possible need for confirmation testing
      when using NAATs if the prevalence of C. trachomatis is less than 2%. If the
      sensitivity of an NAAT is 85% and specificity is 99%, in a hypothetical
      population of 10,000 with a prevalence of 2%, the positive predictive value is
      170/268 (63%). A second important issue affecting testing methods and feasibility
      of using NAATs for screening large numbers of individuals is the pooling of urine
      specimens, which has been evaluated in several studies and found to be very
      effective for reducing costs. A research issue for pooling is the determination
      of the most cost-effective prevalence levels for pooling. An additional research
      question is in which populations should a NAAT be used for detection of C.
      trachomatis and N. gonorrhoeae. There are no recommendations for the routine
      screening of men because of the paucity of data showing that this strategy can
      reduce sequelae. The CDC is conducting a multisite study to examine the
      feasibility, acceptability, and usefulness of screening of asymptomatic men.
      There are a few studies have determining cost-effective prevalence threshold
      levels, particularly with NAATs. A recently developed decision analysis model by
      CDC designed to maximize the effectiveness of screening strategies for C.
      trachomatis infections may be useful for decision makers. It is intended to serve
      as an easy and flexible tool to determine cost effectiveness at a local level and
      takes into account positivity rates and test performance characteristics
      (SOCRATES). It is unclear if recurrent infection is caused by true re-infection
      by the same or a different partner or recurrence of initial infection. Recurrence
      may be caused by persistence of C. trachomatis or antibiotic resistance. This
      distinction is of scientific interest because the appropriate intervention
      differs (eg, identification of risk factors for the former and microbiologic
      investigations for the latter). Effective partner management and retesting are
      critical to reducing sequelae of C. trachomatis infection. Screening for C.
      trachomatis infection remains an essential component of C. trachomatis control.
      It is cost effective, most infections are asymptomatic, and symptom-based health
      care seeking and testing identify few of those infected. The likelihood that
      opportunities for screening are missed is high particularly in non-STD clinic
      settings. Local studies using NAATs to determine C. trachomatis prevalence and
      risk factors are helpful to health care providers so they can make evidence-based
      decisions on who to screen. The use of nontraditional, non-clinic-based test
      settings should be explored further. We have focused on summarizing the medical
      evidence regarding recommendations for screening for C. trachomatis. High-risk
      populations for C. trachomatis infection may overlap with populations for other
      STDs, and comprehensive STD prevention programs that involve a range of STD
      service providers are needed to successfully reduce the STD-related health burden
      in the population.

PMID- 14719843
TI  - Behavioral interventions for prevention of sexually transmitted diseases in
      women: a physician's perspective.
AB  - Behavioral interventions to reduce STD risk in heterosexual women have been
      developed and tested in randomized, controlled trials. Some interventions have
      resulted in behavioral changes to reduce STD risk but either did not adequately
      study or did not affect actual rates of STD acquisition. Two studies have
      resulted in behavioral and STD rate changes using different intervention
      techniques (Project SAFE and Project RESPECT). Further studies are underway to
      improve efficacy and assist transfer to the community. Until interventions are
      more widely implemented, individual physicians can assist patients by providing a
      simple STD risk assessment and suggesting alternative behaviors to reduce risk.

PMID- 14719844
TI  - Vulvovaginal candidiasis.
AB  - VVC represents a spectrum of disease. Although there is a clear need for better
      use of diagnostic modalities and development of better treatment alternatives,
      most patients with VVC, even the complicated cases, at least have the perspective
      of achieving adequate control of their symptoms. Future advances, particularly in
      the area of home diagnostics, may help to optimize use of currently available
      medicines.

PMID- 14719845
TI  - Gynecologic consequences of bacterial vaginosis.
AB  - BV is a prevalent sexually associated infection linked to several gynecologic
      complications and acquisition of STDs and acquisition and transmission of HIV. It
      seems that normalization of the vaginal flora may be effective for preventing
      short-term complications. The implications of screening and treating BV to
      prevent long-term complications are less clear and may depend on the availability
      of more effective treatment regimens.

PMID- 14719846
TI  - Critical care infectious disease.
AB  - Septic shock, toxic shock syndrome, acute respiratory distress syndrome, and
      catheter-related infections are conditions in which intensive care management of
      the patient may be necessary. Toxic shock syndrome is a toxin-mediated illness
      that is not limited to young menstruating women and should be considered in women
      and men who present with fever, hypotension, rash, and multiorgan dysfunction.
      Sepsis is the leading cause of death in critically ill patients in the United
      States and is the most common predisposing factor for acute lung injury or acute
      respiratory distress syndrome. Central venous catheters are often a necessity for
      optimal patient care in these critically ill patients.

PMID- 14719847
TI  - Gynecologic issues in the HIV-infected woman.
AB  - Science has made great strides in understanding the management of the many
      gynecologic conditions that affect HIV-positive women with an increased
      frequency. As HIV-infected women's life expectancy continues to lengthen, new
      treatments are necessary for recurring conditions, such as lower genital tract
      neoplasias. The medical field has much to learn about the interaction between sex
      steroids, HIV-infection, and the immune system. As knowledge grows, clinicians
      will be better equipped to counsel women about contraceptive issues, pregnancy,
      and menopause.

PMID- 14719848
TI  - Antiviral and antiretroviral use in pregnancy.
AB  - The history of antiviral and antiretroviral therapy is recent compared with many
      other medical therapies, including traditional antibiotics in pregnancy. There
      are few long-term data on which to base decisions of management in pregnancy.
      Accessing up-to-date information is critical to optimizing the safety of care for
      mothers and their infants. Exposure to medications in pregnancy can be toxic to a
      fetus in a gestational age-dependent manner. Determination of safe medications
      for pregnancy must take into consideration the need for certain medications and
      the possibility of inadvertent exposure in early pregnancy because of unplanned
      pregnancies. This article reviews the most commonly used antiviral and
      antiretroviral agents and places emphasis on the issues regarding use in
      pregnancy.

PMID- 14719849
TI  - Treatment of sexually transmitted diseases in women.
AB  - Guidelines for the treatment of patients with sexually transmitted infection are
      developed by the Centers for Disease Control and Prevention after consultation
      with a group of professionals knowledgeable in the field. This article briefly
      introduces various infections, reviews new diagnostic information, and presents
      the latest guidelines for therapy. All recommended and alternative regimens are
      drawn from the most recent treatment guidelines. Although this article focuses
      primarily on therapy, it also emphasizes the importance of counseling and
      prevention. Clinicians have the opportunity and obligation to provide education
      and counseling to patients. Prevention messages should be tailored to the
      individual patient with consideration given to her specific risk behaviors.

PMID- 14719850
TI  - Pelvic inflammatory disease: new diagnostic criteria and treatment.
AB  - PID is a common infection in reproductive-age women that presents an enormous
      public health and economic burden. It is responsible for much short- and long
      term morbidity that may necessitate interventions subsequent to the original
      infection. Mild PID seems to be much more common than severe or "classic" PID,
      and the importance of early recognition and treatment cannot be understated.
      Current treatment regimens seem to be effective in terms of immediate clinical
      efficacy. As we learn more about the frequency and importance of subclinical PID,
      the true burden of upper genital tract infection upon reproductive age women
      continues to be elucidated.

PMID- 14719851
TI  - Sexually transmitted infections and contraceptives: selective issues.
AB  - It is important to examine the successful completed research and use it to move
      forward in practice to halt the almost 50% unintended pregnancy rate in the
      United States and the continued worldwide epidemic of HIV and other STIs. A
      significant development has been the evidence supporting the IUD as a valuable
      contraceptive option available to many women, including women who are HIV
      infected, with no increased risks of infertility or PID. Evidence exists that
      OCPs may increase chlamydial infection acquisition and cervicitis, but it is
      unlikely that OCP use is associated with PID. The lack of female-controlled dual
      method protection remains a void, but with the introduction of products such as
      FemCap and Reality condom and the continuing progress of microbicides and
      spermicides, the future is brighter. Clearly research into the interactions of
      STIs and contraceptives must continue to discern how best to approach a
      resolution to these public health concerns that affect women and the global
      population.

PMID- 14719852
TI  - Human papillomavirus infections: diagnosis, treatment, and hope for a vaccine.
AB  - HPV infections are common, with millions of Americans infected. Common
      gynecologic manifestations of HPV infection include genital warts and cervical
      neoplasia. The CDC recently issued guidelines for the treatment of genital warts.
      Gynecologists should be familiar with these therapies and their potential short
      comings. A recently reported clinical trial has raised hopes that HPV and its
      sequelae may be prevented by vaccination.

PMID- 14719853
TI  - Acute mountain sickness in Iranian trekkers around Mount Damavand (5671 m) in
      Iran.
AB  - BACKGROUND: Many trekkers up Mount Damavand run the risk of developing acute
      mountain sickness (AMS); however, not much is documented concerning the incidence
      of AMS and its related factors within this population. OBJECTIVE: We designed
      this study to determine the incidence and risk factors for AMS in trekkers around
      Mount Damavand in Iran. METHODS: Symptoms of AMS and the contributing factors
      were assessed in the course of 6 weeks in summer 2000. Standard Lake Louise
      questionnaires were administered to 459 subjects, all of whom were trekkers. The
      questionnaires were filled out in 3 steps, first at 2900 m and then during both
      ascent and descent at 4200 m. RESULTS: The overall incidence of AMS was 60.8%.
      The incidence was higher in residents who lived at an altitude less than 600 m,
      amateur trekkers, those with a previous history of AMS, those with a history of
      AMS at ascent to Damavand, and those with night ascents (6 PM to midnight).
      Incidence was weakly dependent on rate of ascent (from 2900 m up to 4200 m in
      less than 4 hours) and sleep at 4200 m. No significant association was found
      between AMS and sex, age, body mass index, height, weight, smoking, weight of
      knapsacks, or the spent time in the shelter (at 4200 m). CONCLUSIONS: We conclude
      that the incidence of AMS is high in Iranian trekkers ascending Mount Damavand.
      Some of the contributing factors are preventable, so we suggest considering an
      educational program for trekkers to high altitudes in Iran.

PMID- 14719854
TI  - Serum sickness following administration of Antivenin (Crotalidae) Polyvalent in
      181 cases of presumed rattlesnake envenomation.
AB  - OBJECTIVE: To describe the incidence and characteristics of serum sickness (SS)
      following administration of Wyeth Antivenin (Crotalidae) Polyvalent (ACP).
      METHODS: A retrospective chart review was conducted involving presumed
      rattlesnake bite victims referred to our poison center. Serum sickness was
      defined as unexplained rash developing 3 to 21 days following the administration
      of ACP. Patients were monitored until complete resolution of all symptoms. Data
      collected included total number of ACP vials administered, associated signs and
      symptoms, duration of signs and symptoms, and medications used to treat SS.
      RESULTS: Of the 181 cases included in our study, SS occurred in 102 (56%)
      patients. The frequency of SS in patients receiving fewer than 20, 20 to 29, 30
      to 39, or 40 or more vials was 34%, 36%, 88%, and 100%, respectively. Duration of
      SS averaged 6.1 days (range, 1-21 days). Associated symptoms included subjective
      fever (49%), arthralgia (20%), and pruritus (40%). Reported medications used
      included prednisone (98%), antihistamines (92%), and histamine-2 blockers (3%).
      CONCLUSIONS: Serum sickness following administration of Wyeth ACP is common, with
      a strong correlation between ACP dosage and SS frequency.

PMID- 14719855
TI  - Electrocardiographic evidence for right heart strain in asymptomatic children
      living in Tibet--a comparative study between Han Chinese and ethnic Tibetans.
AB  - OBJECTIVE: To compare ethnic Tibetan children with Han Chinese migrants for signs
      of right ventricular strain using electrocardiography (ECG) that would suggest
      chronic hypoxia at altitudes of 3500 to 4500 m above sea level. METHODS: One
      hundred thirty-five asymptomatic school children aged 7 to 12 years were assessed
      for height, weight, and blood pressure and underwent a single ECG at 2 centers at
      3500 and 4500 m. A questionnaire was given to parents to provide demographic data
      with relevant medical history. RESULTS: There was a high prevalence of right
      ventricular strain on ECG for both Tibetan and Han children (33%) with no
      significant difference between the 2 ethnic groups or sexes. CONCLUSIONS: Other
      studies showing higher observed rates of symptomatic chronic altitude sickness in
      Han Chinese children suggest that other extracardiologic factors play a role in
      the pathogenesis of the disease.

PMID- 14719856
TI  - A case of cerebral sinus thrombosis developed during a high-altitude expedition
      to Gasherbrum I.
AB  - We report a case of cerebral sinus thrombosis, which is a rare but serious
      complication that may develop during high-altitude climbing. A climber who
      reached the summit of Gasherbrum I (8068 m) suffered from motor weakness and gait
      disturbance as he descended from the peak. Within a few days, the symptoms
      progressed until he could not walk. Following a difficult and week-long rescue
      mission by his colleagues, he was hospitalized and diagnosed with thrombosis at
      the superior sagittal and right transverse sinuses. Climbers and rescuers should
      know the risk factors of this complication, such as hemoconcentration,
      procoagulability, and dehydration.

PMID- 14719857
TI  - Regional vs systemic antivenom administration in the treatment of snake venom
      poisoning in a rabbit model: a pilot study.
AB  - OBJECTIVE: To develop a model that compares 2 different routes of antivenom
      administration (standard intravenous [IV] administration vs regional
      administration below a tourniquet) to assess their ability to limit muscle
      necrosis in a rabbit model of rattlesnake venom poisoning. METHODS: New Zealand
      white rabbits were randomly assigned to 4 groups. All animals underwent general
      anesthesia and were then injected intramuscularly (IM) with a sublethal dose of
      western diamond-back rattlesnake (Crotalus atrox) venom in the right thigh and a
      similar volume of normal saline (NS) control in the left thigh. Thirty minutes
      later, standard treatment group animals (n = 4) received 1 vial of reconstituted
      Antivenin (Crotalidae) Polyvalent (ACP) and 10 mL of NS through an ear vein.
      Experimental treatment group animals (n = 4) had their lower extremities
      exsanguinated and isolated by arterial tourniquets. One vial of ACP was then
      given through a distal IV in the envenomed extremity, and 10 mL of NS was given
      through an IV in the sham extremity. Tourniquets were removed 30 minutes later.
      Positive control group animals (n = 2) similarly had their lower extremities
      exsanguinated and isolated by tourniquets. They then received 10 mL of NS through
      distal IVs in each lower extremity. Tourniquets were again removed after 30
      minutes. Negative control group animals (n = 2) received 2 doses of NS only (10
      mL each) through an ear vein. Serum creatinine phosphokinase (CPK) levels were
      drawn at baseline and 48 hours following venom injection. At 48 hours, the
      animals were injected with technetium pyrophosphate. Two hours later, they were
      euthanized, and the lower extremities were scanned to determine levels of
      radionucleotide uptake in envenomed muscles compared to contralateral sham
      injected muscles. The anterior thigh muscle groups were then removed, fixed,
      stained, sectioned, and analyzed in a blinded fashion by a veterinary pathologist
      for muscle necrosis grading. RESULTS: There was no evidence of statistically
      significant differences in changes in serum CPK levels (from baseline to 48
      hours), technetium pyrophosphate uptake ratios (right leg/left leg), or muscle
      necrosis indices in any 2-group analysis. CONCLUSIONS: Results of this pilot
      study do not suggest any beneficial effect of ACP, in the dose and routes used,
      in limiting local muscle necrosis following IM rattlesnake venom poisoning in the
      rabbit model.

PMID- 14719858
TI  - Wilderness event medicine.
AB  - OBJECTIVES: Wilderness Event Medicine (WEM), that is, the care of large groups of
      people participating in events in remote areas, is a rapidly growing subspecialty
      of wilderness medicine. Our goals are to report the injury rates from one
      wilderness event and to suggest ways to advance this emerging field. METHODS: We
      describe a 1-day wilderness hike and compare the injury rates from this one event
      with rates from other urban and wilderness events. RESULTS: Of the total 350
      hikers, 6 persons presented for medical evaluation (5 dehydration and 1
      orthopedic), yielding a rate of 17 evaluations per 1000 person-days of exposure.
      Only 1 person (or 2.9 per 1000) required medical assistance beyond oral
      rehydration. These rates are comparable to rates reported for urban events and
      other wilderness activities. CONCLUSIONS: According to very limited reports, the
      rates of injuries in wilderness events are similar to those for urban events. We
      recommend defining a wilderness event as an event with more than 200 participants
      and where the time from injury to care at a medical facility is likely to be
      greater than 1 hour. We also suggest the creation of a database of wilderness
      events, including standardized terms for the descriptions of activities, terrain,
      injuries, and medical response. Such a database could be used to help event
      planners anticipate and perhaps prevent injuries and to prepare effectively for
      those injuries that do occur.

PMID- 14719859
TI  - Effects of a 3-month endurance event on physical performance and body
      composition: the G2 trans-Greenland expedition.
AB  - OBJECTIVE: Prolonged physical exertion with inadequate time for recuperation may
      result in an overtraining phenomenon characterized by reduced physical strength
      and endurance capacity. We tested the hypothesis that highly motivated men pushed
      to the limits of their endurance capacity for 3 months would suffer physical
      breakdown characterized by loss of lean mass and reduced physical performance
      capacity. METHODS: Two well-trained men (VO2max > 60 mL/kg/min), aged 25 years,
      completed an unsupported, 2928-km, south-to-north ski trek across Greenland in 86
      days. The trek involved ski marching, typically for 9 h/d, pulling sleds
      initially containing 150 kg and a high-fat (60%) energy-dense diet of 25.1 MJ/d.
      Body composition and physical performance data were collected 14 days before and
      4 days after the trek. RESULTS: Energy expenditure based on doubly labeled water
      during three 2-week periods ranged from 28.3 and 34.6 MJ/d in rugged terrain to
      14.6 and 16.1 MJ/d during travel on flat terrain for subjects 1 and 2,
      respectively. Both men lost weight, completing the trek with low-normal fat
      stores (approximately 13% body fat). The lighter man gained 0.6 kg lean mass,
      while the heavier man lost 1.4 kg lean mass and a larger amount of fat weight
      (7.0 kg). Most performance measures showed trivial changes within the errors of
      measurement and test reproducibility, indicating no loss of endurance capacity,
      but anaerobic tests (Wingate and vertical jump) were markedly reduced. Markers of
      metabolic status, including oral glucose tolerance tests, indicated no functional
      impairments. CONCLUSIONS: Although the number of subjects was limited, this
      observational study demonstrated that well-trained and experienced long-distance
      ski trekkers who eat an adequate high-calorie diet can perform endurance treks in
      severe cold, with little or no loss of lean mass and physical capability.

PMID- 14719860
TI  - Piranha attacks on humans in southeast Brazil: epidemiology, natural history, and
      clinical treatment, with description of a bite outbreak.
AB  - There are many tales describing ferocious schools of piranha attacking humans,
      but there are few scientific data supporting such behavior. The very few
      documented instances of humans attacked and eaten by piranha schools include 3
      that occurred after death by other causes (eg, heart failure and drowning). These
      predaceous fishes, however, do occasionally injure bathers and swimmers in lakes
      and rivers. The characteristic profile of most injuries is a single bite per
      victim, generally related to the fish defending its brood. This paper describes
      an outbreak of piranha bites in a dammed river portion in southeast Brazil. The
      outbreak was caused by the speckled piranha, Serrasalmus spilopleura, a
      widespread species which benefits from the growing tendency of damming rivers all
      over Brazil. This article focuses on the epidemiological and clinical aspects of
      the injuries, as well as on piranha biology, to gain a better understanding of
      the natural history of bite outbreaks.

PMID- 14719861
TI  - Injuries associated with whitewater rafting and kayaking.
AB  - Whitewater rafting and kayaking are growing exponentially in popularity, with
      almost 10 million rafters and 2 to 3 million kayakers, yet little has been
      published concerning the safety or hazards of these activities. This article
      reviews the demographics of such injuries and the types of injuries commonly
      encountered. Fortunately, fatalities are uncommon in these activities, with
      rafting and kayaking fatalities occurring at a rate of 0.55 and 2.9 per 100000
      user days, respectively. Injury rates for kayaking and rafting are 3 to 6 and
      0.26 to 2.1 per 100000 boating days, respectively. Acute injuries in kayaking are
      usually due to the transferred force of the water on the upper extremity, most
      often the shoulder, or the impact on an object while "swimming." Acute rafting
      injuries are more often due to contact with another rafter's paddle or other
      equipment; the next most common injury is the rafter hitting an object while
      "swimming." Chronic injuries are very uncommon in rafting but account for 25% to
      40% of all kayaking injuries and are most often either shoulder or wrist
      complaints.

PMID- 14719862
TI  - Olaf Larsell's "medical aspects of the Lewis and Clark expedition"--a commentary.

PMID- 14719863
TI  - Medical aspects of the Lewis and Clark expedition (1804-1806). 1947.

PMID- 14719864
TI  - An introduction to the Medical Wilderness Adventure Race (MedWAR).

PMID- 14719865
TI  - The Medical Wilderness Adventure Race (MedWAR): a 2-year perspective on a unique
      learning experience.

PMID- 14719866
TI  - Migraines and high-altitude headaches.

PMID- 14719867
TI  - Clinical aspects of Plasmodium falciparum.

PMID- 14719868
TI  - On-line analysis of organic components in fine and ultrafine particles by
      photoionization aerosol mass spectrometry.
AB  - A new method, photoionization aerosol mass spectrometry (PIAMS), is described for
      real-time analysis of organic components in airborne particles below
      approximately 300 nm in diameter. Particles are focused through an aerodynamic
      lens assembly into the mass spectrometer where they are collected on a probe in
      the source region. After a sufficient amount of sample has been collected, the
      probe is irradiated with a pulsed infrared laser beam to vaporize organic
      components, which are then softly ionized with coherent vacuum ultraviolet
      radiation at 118 nm (10.5 eV). Since the photon energy is close to the ionization
      energies of most organic compounds, fragmentation is minimized. Both aliphatic
      and aromatic compounds of atmospheric relevance are detected and quantified in
      the low- to midpicogram range. The photoionization signal intensity increases
      linearly with the amount of material sampled and is independent of particle size.
      The fragmentation induced by laser desorption is greater than that observed with
      thermal vaporization, suggesting that the internal energy imparted by the former
      is greater. Although some molecular fragmentation is observed, mass spectra from
      common sources of ambient organic aerosol are distinguishable and consistent with
      previous off-line measurements by gas chromatography/mass spectrometry. These
      results illustrate the potential of PIAMS for molecular characterization of
      organic aerosols in ambient and smog chamber measurements.

PMID- 14719869
TI  - Optically timed submillimeter time-of-flight mass spectrometry.
AB  - We demonstrate that using intense femtosecond laser pulses to optically time ion
      flight can lead to a miniature time-of-flight mass spectrometer. After laser
      ionization, the molecular ion is accelerated by a static electric field and
      detected using a second, delayed laser pulse. The relative positions of the two
      laser foci determine the ion flight distance while the time separation of the
      laser pulses fixes the ion flight time. We mass-resolve CS(2) or C(6)H(6)
      isotopes after a flight distance of 360 microm using either double ionization or
      Coulomb explosion detection.

PMID- 14719870
TI  - An alternative to tandem mass spectrometry: isoelectric point and accurate mass
      for the identification of peptides.
AB  - The traditional approach to the identification of peptides in complex biological
      samples integrally involves the use of tandem mass spectrometry to generate a
      unique fragmentation pattern in order to accurately assign its identity to a
      particular protein. In this article we describe the theoretical basis for a new
      paradigm for the identification of peptides and proteins. This methodology
      employs the use of accurate mass and peptide isoelectric point (pI) as
      identification criteria, and represents a change in focus from current tandem
      mass spectrometry-dominated approaches. A mathematical derivation of the false
      positive rate associated with accurate mass and pI measurements is presented to
      demonstrate the utility of the technique. The equations for calculation of the
      experimental false positive rate allow for the determination of the validity of
      the data. The false positive rate issue examined in detail here is not restricted
      to accurate mass-based approaches, but also has application to the tandem mass
      spectrometry community as well. The theoretical proteomes of Escherichia coli and
      Rattus norvegicus are used to evaluate the efficacy of this approach. The power
      of the technique is demonstrated by analyzing a series of peptides with the same
      monoisotopic masses but with differing isoelectric points. Finally, the speed of
      algorithm when combined with the experimental peptide analysis has the potential
      to rapidly accelerate the protein identification process.

PMID- 14719871
TI  - Prediction of posttranslational modifications using intact-protein mass
      spectrometric data.
AB  - We present a Web-based application that uses whole-protein masses determined by
      mass spectrometry to identify putative co- and posttranslational proteolytic
      cleavages and chemical modifications. The protein cleavage and modification
      engine (PROCLAME) requires as input an intact mass measurement and a precursor
      identification based on peptide mass fingerprinting or tandem mass spectrometry.
      This approach predicts mass-modifying events using a depth-first tree search,
      bounded by a set of rules controlled by a custom-built fuzzy logic engine, to
      explore a large number of possible combinations of modifications accounting for
      the experimental mass. Candidates are saved during a search if they are within a
      user-specified instrument mass accuracy; the total number of possible candidates
      searched is based on a specified fuzzy cutoff score. Candidates are scored and
      ranked using a simple probabilistic model. There is generally not enough
      information in an intact mass measurement to determine a single unique protein
      characterization; however, the program provides utility by expediting the
      identification of sets of putative events consistent with the mass data and
      ranking them for further investigation. This approach uses a simple, intuitive
      rule base and lends itself to discovery of unannotated posttranslational events.
      We have assessed the program with both in silico-generated test data and with
      published data from an analysis of large ribosomal subunit proteins, both from
      the yeast S. cerevisiae. Results indicate a high degree of sensitivity and
      specificity in characterizing proteins whose masses resulted from reasonable
      proteolysis and covalent modification scenarios. The application is available on
      the web at http://proclame.unc.edu.

PMID- 14719872
TI  - Electrodes modified with monoolein cubic phases hosting laccases for the
      catalytic reduction of dioxygen.
AB  - An enzyme-catalyzed process has been used for dioxygen monitoring. The enzymes
      were two different laccases (p-diphenol:dioxygen oxidoreductases), chosen as
      catalysts for dioxygen reduction. The laccases were immobilized in a liquid
      crystalline cubic phase formed with monoolein. The structures of the cubic
      phases, both with and without enzymes, were established using small-angle X-ray
      scattering. The catalytic reduction of dioxygen was performed using a glassy
      carbon electrode modified with cubic phases containing the enzymes. The modified
      electrode was used as a dioxygen sensing system, based on the increasing
      reduction current of a suitable electrochemical probe in the presence of
      dioxygen.

PMID- 14719874
TI  - Capillary electrophoresis microchip with a carbon nanotube-modified
      electrochemical detector.
AB  - Significant improvements in the performance of a capillary electrophoresis (CE)
      microchip with an electrochemical detector are observed using a carbon nanotube
      (CNT)-modified working electrode. The CNT-modified electrode allows CE
      amperometric detection at significantly lower operating potentials and yields
      substantially enhanced signal-to-noise characteristics. The electrocatalytic
      detection is coupled to resistance to surface fouling and hence enhanced
      stability. Such advantages are illustrated in connection with several classes of
      hydrazine, phenol, purine, and amino acid compounds. Substantial minimization of
      surface fouling effects has been demonstrated in connection with the monitoring
      of phenol and tyrosine. Factors affecting the performance of the new CNT detector
      were assessed and optimized. CNTs from different sources are evaluated, and the
      effect of an anodic pretreatment is explored. The broad and significant catalytic
      activity exhibited by CNT-based CE detectors indicates great promise for a wide
      range of bioanalytical and environmental applications.

PMID- 14719873
TI  - Glucose biosensor based on the microcantilever.
AB  - Diagnosis and management of diabetes require quantitative and selective detection
      of blood glucose levels. We report a technique for micromechanical detection of
      biologically relevant glucose concentrations by immobilization of glucose oxidase
      (GOx) onto a microcantilever surface. Microfabricated cantilevers have
      traditionally found utility in atomic force microscope imaging. During the past
      decade, however, microcantilevers have been increasingly used as transducers in
      chemical-sensing systems. This paper describes the combination of this technology
      with enzyme specificity to construct a highly selective glucose biosensor. The
      enzyme-functionalized microcantilever undergoes bending due to a change in
      surface stress induced by the reaction between glucose in solution and the GOx
      immobilized on the cantilever surface. Experiments were carried out under flow
      conditions. The common interferences for glucose detection in other detection
      schemes have been tested and have shown to have no effect on the measurement of
      blood glucose level by this technique.

PMID- 14719875
TI  - Affinity two-phase partitioning in acoustically levitated drops.
AB  - Miniaturized (<1 microL) biospecific affinity two-phase partitioning in an
      acoustically levitated drop is described. Miniaturization commonly gives
      unfavorable surface/volume ratios, but in the levitation approach adsorption
      problems are minimized since the only surrounding wall is the liquid/air
      interface of the drop. Biotinylated liposomes were partitioned in aqueous
      poly(ethylene glycol)/dextran two-phase drops with NeutrAvidin-dextran as the
      affinity ligand. A two-phase drop was trapped and manipulated in a node of a
      standing ultrasonic wave. Alternatively, a two-phase system was formed by
      levitation and evaporation of a polymer one-phase drop. Phase mixing was achieved
      by adjusting the ultrasonic field and phase separation by readjusting the field.
      NeutrAvidin-dextran brought about the redistribution of biotinylated liposomes
      from the poly(ethylene glycol)-rich phase into the dextran-rich phase. Thus, an
      entire affinity two-phase separation procedure, including mixing of the phases
      and incubation to allow affinity interactions to develop under constant volume,
      followed by phase separation under controlled evaporation, can be performed in a
      single levitated drop. This miniaturized technique would allow the separation of
      biologically active membranes or organelles from individual cells for analysis.

PMID- 14719876
TI  - Microchemical element imaging of yeast and human cells using synchrotron X-ray
      microprobe with Kirkpatrick-Baez optics.
AB  - Trace element imaging and speciation analysis in cells and subcellular
      compartments is a challenging and important objective for modern analytical
      chemistry in order to better understand the biological chemistry of essential and
      toxic elements. A focusing system based on Kirkpatrick-Baez design optics mounted
      on a synchrotron radiation scanning X-ray microscope has been developed at the
      ESRF and was used for trace element quantitative imaging in single cells. The
      focused microbeam (1.3 x 3.2 microm(2)) obtained in that way led to a photon flux
      as bright as 1.5 x 10(11) photons/s at 14 keV. The absolute detection limit of
      this analytical probe, as measured on standard reference materials, was shown to
      be 2 x 10(-)(17) g for most elements. Chemical maps of human carcinoma and of
      Saccharomyces cerevisiae cells were obtained for minor (P, S, Cl, K) and trace
      elements (Fe, Zn). Within human cancer cells, chemical elements are homogeneously
      distributed at the current spatial resolution and correlated with the sample's
      mass, except Fe, which shows micrometer-sized structures around the cell nucleus,
      and Zn, which slightly concentrates in the nucleus, while chemical maps of S.
      cerevisiae show homogeneous pattern distribution at the cellular level.

PMID- 14719877
TI  - Direct sampling from muscle cross sections for electrophoretic analysis of
      individual mitochondria.
AB  - Muscle is a highly heterogeneous tissue. Practical approaches to sample
      selectively small regions of muscle cross sections would help to effectively
      utilize analytical techniques on muscle studies while taking into account tissue
      heterogeneity. In this report, semimembranosus muscle tissue cross sections were
      directly sampled and analyzed by capillary electrophoresis (CE) with laser
      induced fluorescence detection (LIF). Prior to CE-LIF analysis, a small region in
      the muscle cross section was stained with 10-nonyl acridine orange (NAO) which is
      a mitochondrion-selective fluorescent probe known to form a stable complex with
      cardiolipin, a phospholipid found only in mitochondria. By micromanipulation, the
      injection end of the capillary was brought into contact with the tissue
      exhibiting fluorescently labeled mitochondria. Sampling from a region similar in
      size to the cross section of a single fiber was carried out by applying 11 kPa of
      negative pressure for 3 s. When an electric field of -200V/cm was applied,
      fluorescently labeled mitochondria electromigrated and were individually detected
      by postcolumn LIF detection. For each sample, the electropherogram displays a
      migration time window with a collection of narrow peaks. The collection of
      individual peak measurements is represented as a distribution of individual
      intensities related to cardiolipin content of mitochondria and a distribution of
      individual electrophoretic mobilities. Positioning the capillary injection end
      was sufficiently spatially accurate to deplete mitochondria in the sampled region
      upon repetitive injections. Treatment of a muscle cross section with a protease
      (trypsin) prior to mitochondria sampling resulted in a higher number of detected
      mitochondria, suggesting that one of the effects of this enzyme is a partial
      digestion of the muscles myofibrils, which eases the release of interfibrillar
      mitochondria entangled within these fibers. The protease treatment also resulted
      in changes to the electrophoretic mobility distribution of individual
      mitochondria, which may imply that partial digestion of proteins bound to the
      mitochondria contributes to the alteration in the electrophoretic mobility of
      mitochondria. The ability to sample a region as small as a single muscle fiber
      cross section and its direct CE-LIF analysis opens exciting possibilities for the
      direct analysis of muscle biopsies and mapping the mitochondrial electrophoretic
      properties in highly heterogeneous tissues.

PMID- 14719878
TI  - Fe isotope variations in natural materials measured using high mass resolution
      multiple collector ICPMS.
AB  - We present the first measurements of Fe isotope variations in chemically purified
      natural samples using high mass resolution multiple-collector inductively coupled
      plasma source mass spectrometry (MC-ICPMS). High mass resolution allows
      polyatomic interferences at Fe masses to be resolved (especially, (40)Ar(14)N(+),
      (40)Ar(16)O(+), and (40)Ar(16)OH(+)). Simultaneous detection of Fe isotope ion
      beams using multiple Faraday collectors facilitates high-precision isotope ratio
      measurements. Fe in basalt and paleosol samples was extracted and purified using
      a simple, single-stage anion chemistry procedure. A Cu "element spike" was used
      as an internal standard to correct for variations in mass bias. Using this
      procedure, we obtained data with an external precision of 0.03-0.11 per thousand
      and 0.04-0.15 per thousand for delta(56/54)Fe and delta(57/54)Fe, respectively
      (2sigma). Use of Cu was necessary for such reproducibility, presumably because of
      subtle effects of residual sample matrix on mass bias. These findings demonstrate
      the utility of high-resolution MC-ICPMS for high-precision Fe isotope analysis in
      geologic and other natural materials. They also highlight the importance of
      internal monitoring of mass bias, particularly when using routine methods for Fe
      extraction and purification.

PMID- 14719879
TI  - An interface for direct analysis of (14)c in nonvolatile samples by accelerator
      mass spectrometry.
AB  - We describe here apparatus and methods for direct analysis of (14)C in biological
      specimens by accelerator mass spectrometry (AMS). Liquid samples, including
      plasma and urine, are deposited by pipet into a bed of CuO powder that fills a
      space within a rigid, refractory support. Volatile components are removed under
      reduced pressure prior to analysis. The CuO matrix is locally heated with an
      infrared laser while it is contained within a sealed chamber that is swept with
      He carrier gas. Heating induces combustion of the applied sample, and the carrier
      gas transports the CO(2) that is formed to the AMS instrument's ion source, which
      is appropriately modified for use with CO(2). A rodent study of drug clearance
      with [(14)C]-acetaminophen was performed to provide plasma and urine specimens,
      which were analyzed with this overall approach and by liquid scintillation
      counting for comparison. Results presented here confirm the potential utility of
      laser-induced sample combustion as an alternative to graphite production for AMS
      analysis of (14)C. Anticipated benefits of the present approach include reduced
      risk of sample cross-contamination, decreased analysis time, and greater
      compatibility with robotics.

PMID- 14719880
TI  - Nonaqueous capillary electrophoresis-mass spectrometry of synthetic polymers.
AB  - In this work, the separation and characterization of ionizable organic polymers
      nonsoluble in water is carried out using nonaqueous capillary electrophoresis-ion
      trap mass spectrometry (NACE-MS). The polymers studied are poly(N(epsilon)
      trifluoroacetyl-l-lysine) (poly(TFA-Lys)) obtained by ring-opening polymerization
      of the corresponding N-carboxyanhydride. Different parameters (i.e., liquid
      sheath nature and flow rate, electrospray temperature, and separation buffer
      composition) are optimized in order to obtain both an adequate CE separation and
      a high MS signal of the samples under study. The optimum NACE-MS separation
      conditions allow the molecular mass characterization of poly(TFA-Lys) up to a
      degree of polymerization of 38. NACE-MS provides interesting information on the
      chemical structure of (i). the polymer end groups and (ii). other final
      byproducts. The MS spectra obtained by using this CE-MS protocol confirm that the
      polymerization was initiated by the reaction of n-hexylamine (initiator) on the
      monomer. CE-MS-MS and CE-MS-MS-MS results demonstrate that two different
      termination reactions occurred during the polymerization process leading to the
      transformation of the reactive amine end group into a carboxylic or a formyl
      groups. Byproducts such as 3-hydantoinacetic acid or diketopiperazine were also
      detected. To our knowledge, this is the first work in which the great
      possibilities of NACE-MS and NACE-MS(n) for characterizing synthetic polymers are
      demonstrated.

PMID- 14719881
TI  - Integrated sample preparation and MALDI mass spectrometry on a microfluidic
      compact disk.
AB  - High-throughput microfluidic processing of protein digests integrated with matrix
      assisted laser desorption/ionization (MALDI) mass spectrometry on a compact disk
      (CD) is described. Centrifugal force moves liquid through multiple
      microstructures, each containing a 10-nL reversed-phase chromatography column.
      The CD enables parallel preparation of 96 samples with volumes ranging from one
      to several microliters. The peptides in the digests are concentrated, desalted,
      and subsequently eluted from the columns directly into MALDI target areas (200 x
      400 microm) on the CD using a solvent containing the MALDI matrix. After
      crystallization, the CD is inserted into the MALDI instrument for peptide mass
      fingerprinting and database identification at a routine sensitivity down to the
      200-amol level. Detection of proteolytic peptides down to the 50-amol level is
      demonstrated. The success rate of the CD technology in protein identification is
      about twice that of the C(18) ZipTips and standard MALDI steel targets. The CDs
      are operated using robotics to transfer samples and reagents from microcontainers
      to the processing inlets on the disposable CD and spinning to control the
      movement of liquid through the microstructures.

PMID- 14719882
TI  - Surface-induced dissociation of ions produced by matrix-assisted laser
      desorption/ionization in a fourier transform ion cyclotron resonance mass
      spectrometer.
AB  - Intermediate pressure matrix-assisted laser desorption/ionization (MALDI) source
      was constructed and interfaced with a 6-T Fourier transform ion cyclotron
      resonance mass spectrometer (FT-ICR MS) specially configured for surface-induced
      dissociation (SID) studies. First MALDI-SID results in FT-ICR are presented,
      demonstrating unique advantages of SID over conventional FT-ICR MS ion activation
      techniques for structural characterization of singly protonated peptide ions.
      Specifically, we demonstrate that SID on a diamond surface results in a
      significantly better sequence coverage for singly protonated peptides than SORI
      CID. A combination of two effects contributes to the improved sequence coverage:
      shattering of peptide ions on surfaces opens up a variety of dissociation
      channels at collision energies above 40 eV, and second, wide internal energy
      distribution deposited by collision with a stiff diamond surface provides an
      efficient mixing between the primary reaction channels that are dominant at low
      internal energies and extensive fragmentation at high internal excitation that
      results from shattering. Activation of MALDI-generated ions by collisions with
      surfaces in FT-ICR MS is a new powerful method for characterization and
      identification of biomolecules

PMID- 14719883
TI  - Development of an ordered array of optoelectrochemical individually readable
      sensors with submicrometer dimensions: application to remote
      electrochemiluminescence imaging.
AB  - A novel array of optoelectrochemical submicrometer sensors for remote
      electrochemiluminescence (ECL) imaging is presented. This device was fabricated
      by chemical etching of a coherent optical fiber bundle to produce a nanotip
      array. The surface of the etched bundle was sputter-coated with a thin layer of
      indium tin oxide in order to create a transparent and electrically conductive
      surface that is insulated eventually by a new electrophoretic paint except for
      the apex of the tip. These fabrication steps produced an ordered array of
      optoelectrochemical sensors with submicrometer dimensions that retains the
      optical fiber bundle architecture. The electrochemical behavior of the sensor
      array was independently characterized by cyclic voltammetry and ECL experiments.
      The steady-state current indicates that the sensors are diffusively independent.
      This sensor array was further studied with a co-reactant ECL model system, such
      as Ru(bpy)(3)(2+)/TPrA. We clearly observed an ordered array of individual ECL
      micrometer spots, which corresponds to the sensor array structure. While the
      sensors of the array are not individually addressable electrochemically, we could
      establish that the sensors are optically independent and individually readable.
      Finally, we show that remote ECL imaging is performed quantitatively through the
      optoelectrochemical sensor array itself.

PMID- 14719884
TI  - A robust technique for assembly of nucleic acid hybridization chips based on
      electrochemically templated chitosan.
AB  - A nucleic acid hybridization assay was assembled onto a robust and readily
      addressable silicon-based chip using polysaccharide chitosan as a scaffold for
      the covalent coupling of probe DNA to the chip's surface. Chitosan is a unique
      polymer, ideally suited for this application because its net charge and
      solubility are pH dependent. Specifically in this work, gold-patterned electrodes
      were created using standard photolithographic techniques, chitosan was
      electrodeposited in a spatially resolved manner onto the polarized electrodes,
      probe DNA was covalently assembled onto the chitosan, and both DNA:DNA and
      DNA:mRNA hybridization detection schemes were evaluated. Hybridization of target
      nucleic acid was quantifiable, reproducible, and robust; the surface was
      regenerated and rehybridized up to eight times without loss of signal. Finally,
      transcriptional upregulation of the Escherichia coli chaperone, DnaK, which is an
      indicator of cellular stress, was observed using the hybridization chip sandwich
      assay. Thus, this method enables rapid and facile monitoring of gene expression
      in a format that is reusable and requires minimal reagent quantities.

PMID- 14719885
TI  - Reagentless detection and classification of individual bioaerosol particles in
      seconds.
AB  - The rapid chemical analysis of individual cells is an analytical capability that
      will profoundly impact many fields including bioaerosol detection for biodefense
      and cellular diagnostics for clinical medicine. This article describes a mass
      spectrometry-based analytical technique for the real-time and reagentless
      characterization of individual airborne cells without sample preparation. We
      characterize the mass spectral signature of individual Bacillus spores and
      demonstrate the ability to distinguish two Bacillus spore species, B.
      thuringiensis and B.atrophaeus, from one another very accurately and from the
      other biological and nonbiological background materials tested with no false
      positives at a sensitivity of 92%. This example demonstrates that the chemical
      differences between these two Bacillus spore species are consistently and easily
      detected within single cells in seconds.

PMID- 14719886
TI  - Nanosecond and femtosecond laser ablation of brass: particulate and ICPMS
      measurements.
AB  - Femtosecond and nanosecond lasers were compared for ablating brass alloys. All
      operating parameters from both lasers were equal except for the pulse duration.
      The ablated aerosol vapor was collected on silicon substrates for particle size
      measurements or sent into an inductively coupled plasma mass spectrometer. The
      diameters and size distribution of particulates were measured from scanning
      electron microscope (SEM) images of the collected ablated aerosol. SEM
      measurements showed that particles ablated using nanosecond pulses were single
      spherical entities ranging in diameter from several micrometers to several
      hundred nanometers. Primary particles ablated using femtosecond ablation were
      approximately 100 nm in diameter but formed large agglomerates. ICPMS showed
      enhanced signal intensity and stability using femtosecond compared to nanosecond
      laser ablation.

PMID- 14719887
TI  - Direct analysis of oxidizing agents in aqueous solution with attenuated total
      reflectance mid-infrared spectroscopy and diamond-like carbon protected
      waveguides.
AB  - A novel approach for the direct detection of oxidizing agents in aqueous solution
      is presented using diamond-like carbon (DLC) protected waveguides in combination
      with attenuated total reflectance (ATR) mid-infrared spectroscopy. Pulsed laser
      deposition was applied to produce high-quality DLC thin films on ZnSe ATR
      crystals with thicknesses of a few 100 nm. Scanning electron microscopy and X-ray
      photoelectron spectroscopy has been used to investigate the surface properties of
      the DLC films including the sp(3)/sp(2) hybridization ratio of the carbon bonds.
      Beside excellent adhesion of the DLC coatings to ZnSe crystals, these films show
      high chemical stability against strongly oxidizing agents. IR microscopy was
      utilized to compare differences in the chemical surface modification of bare and
      protected ATR waveguides when exposed to hydrogen peroxide, peracetic acid, and
      peroxydisulfuric acid. The feasibility of DLC protected waveguides for real-time
      concentration monitoring of these oxidizing agents was demonstrated by measuring
      calibration sets in a concentration range of 0.2-10%. Additionally, principal
      component regression has been applied to analyze multicomponent mixtures of
      hydrogen peroxide, acetic acid, and peracetic acid in aqueous solution. Due to
      high chemical stability and accurate monitoring capabilities, DLC protected
      waveguides represent a novel approach for directly detecting oxidizing agents in
      aqueous solution with promising potential for industrial process analysis.

PMID- 14719888
TI  - Application of nonselective 1D (1)H-(31)P inverse NMR spectroscopy to the
      screening of solutions for the presence of organophosphorus compounds related to
      the chemical weapons convention.
AB  - 1D nonselective (1)H-(31)P HSQMBC, HSQC, and (31)P decoupled HSQC NMR experiments
      were applied to the screening of original OPCW proficiency test samples for the
      presence of organophosphorus (OP) compounds related to the Chemical Weapons
      Convention. The HSQC and HSQMBC spectra are compared to 1D (1)H NMR spectra with
      WET solvent suppression and (31)P[(1)H] spectra of the same samples. The 1D
      nonselective HSQC and HSQMBC experiments are shown to be the most sensitive NMR
      experiments to selectively screen samples for the presence of
      organophosphorus(OP) compounds. These experiments are at least three times more
      sensitive than the (31)P[(1)H] NMR experiment and allow the determination of the
      number of OP compounds present in the sample and their alkyl group bound to the
      phosphorus atom. Samples spiked at the 5-10 ppm level can be screened within an
      hour for the presence of OP compounds, whereas for the (31)P[(1)H] experiments,
      an overnight acquisition is necessary. The sensitivity of the experiments
      decreases in the order (31)P decoupled HSQC, HSQMBC, and HSQC. For the different
      alkyl groups, the sensitivity of these experiments decreases in the order methyl
      approximately isopropyl > ethyl > propyl.

PMID- 14719889
TI  - Quenched phosphorescence as a detection method in capillary electrophoretic
      chiral separations. Monitoring the stereoselective biodegradation of
      camphorquinone by yeast.
AB  - Quenched phosphorescence detection of camphorquinone in cyclodextrin-based
      electrokinetic chromatography provides very favorable detection limits, i.e., 7 x
      10(-)(7) M, 3 orders of magnitude lower than conventional UV absorption detection
      at 200 nm. The detection is based on the dynamic quenching by the analyte of the
      strong phosphorescence emission of brominated naphthalenesulfonate, under
      deoxygenated buffer solution conditions. This approach has been used to detect
      (1S)-(+)- and (1R)-(-)-camphorquinone after enantiomeric separation by CE.
      Although the use of the negatively charged carboxymethyl beta-cyclodextrin (CM
      beta-CD) alone was not successful, the addition of a second, neutral
      cyclodextrin, alpha-CD, provided an adequate enantiomeric separation of
      camphorquinone. Using 25 mM borate buffer (pH 8.5) with 10 mM CM-beta-CD and 20
      mM alpha-CD (applied voltage 20 kV, ambient temperature), the enantiomeric
      separation was performed in approximately 14 min. The chiral method was applied
      to monitor the stereoselectivity of the biotransformation of a racemic mixture of
      camphorquinone by yeast. It was found that the enantiomeric ratio calculated from
      the peak areas in the electropherogram (RSD = 5%) after 24 h of incubation
      decreased from 0.92 for the control solution (culture medium without yeast) to
      0.24 for the culture medium; a similar ratio of 0.25 was observed for cell
      extract solutions. Therefore, racemic camphorquinone is enantioselectively
      degraded by yeast, the biodegradation of (1S)-(+)-camphorquinone being faster
      than that of the (1R)-(-)-enantiomer.

PMID- 14719890
TI  - Parametric time warping.
AB  - A parametric model is proposed for the warping function when aligning
      chromatograms. A very fast and stable algorithm results that consumes little
      memory and avoids the artifacts of dynamic time warping. The parameters of the
      warping function are useful for quality control. They also are easily
      interpolated, allowing alignment of batches of chromatograms based on warping
      functions for a limited number of calibration samples.

PMID- 14719891
TI  - Evaluation of surface-enhanced resonance Raman scattering for quantitative DNA
      analysis.
AB  - The labeling of biological species using dyes has become common practice to aid
      in their detection, and immediate positive identification of specific dyes in
      high dilution is a key requirement. Here the detection by surface-enhanced
      resonance Raman scattering (SERRS) of eight commercially available dye labels
      (ROX, rhodamine 6G, HEX, FAM, TET, Cy3, Cy5, TAMRA) attached to oligonucleotide
      strands is reported. Each of the eight labels was easily detected by using the
      SERRS from silver nanoparticles to produce a unique, molecularly specific
      spectrum. The conditions were optimized to obtain the best signal enhancement,
      and linear concentration graphs at low oligonucleotide concentrations were
      obtained. At higher concentrations (above approximately 10(-)(8) mol dm(-)(3)),
      curvature was introduced into the concentration graphs with the exception of
      rhodamine 6G, TET, and FAM, which gave linearity over the entire concentration
      range studied. Detection limits as low as 0.5 fmol were obtained, with lower
      possible if a smaller sample was analyzed. Investigation was also carried out
      into the effect of a Tris-HCl buffer containing the surfactant Tween 20 to aid in
      the prevention of surface adhesion of the oligonucleotides to the sample vessels
      at ultralow concentrations. The Tween 20 allowed lower detection limits to be
      obtained for each of the labels studied. This study shows that the different dyes
      commonly used with oligonucleotides can give quantitative SERRS at concentration
      levels not possible when the same dyes are used with fluorescence detection.

PMID- 14719893
TI  - Real-time diode laser measurements of vapor-phase benzene.
AB  - An absorption spectrometer equipped with a IV-VI semiconductor tunable mid-IR
      diode laser was used to make sensitive measurements of benzene (C(6)H(6)) gas in
      the 5.1-microm spectral range. Wavelength modulation coupled with second-harmonic
      detection achieved accurate real-time quantification of benzene concentrations
      down to a minimum detection limit of 1 ppmv with an integration time of 4 s. A
      variety of calibrated benzene-sensing measurements were made, including the
      determination of the benzene concentrations in vehicle exhaust and headspace
      vapors from unleaded gasoline and other liquids. Kinetic phenomena, including the
      monitoring of benzene evaporation and absorption/desorption by granulated
      activated carbon were observed with the instrument. Measurements were performed
      that allowed experimental determination of the activation energy for desorption
      of benzene from activated carbon, which was found to be 198 meV/molecule (19.0
      kJ/mol).

PMID- 14719892
TI  - Volatile analytes formed from arsenosugars: determination by HPLC-HG-ICPMS and
      implications for arsenic speciation analyses.
AB  - It is generally accepted that the use of the hydride generation method to produce
      volatile analytes from arsenic compounds is restricted to the two inorganic forms
      (As(III) and As(V)) and the three simple methylated species methylarsonate (MA),
      dimethylarsinate (DMA), and trimethylarsine oxide. We report here that
      arsenosugars, major arsenic compounds in marine organisms, produce volatile
      analytes by the hydride generation (HG) method without a prior
      mineralization/oxidation step and that they can be quantitatively determined
      using HPLC-HG-ICPMS. The hydride generation efficiency depends on the type of
      hydride generation system and is influenced by the concentration of HCl and
      NaBH(4). For the four arsenosugars investigated, the hydride generation
      efficiencies were approximately 21-28% (or 4-6%, depending on the HG system) that
      obtained for As(III) under conditions optimized for As(III). This hydride
      efficiency was less than that shown by MA ( approximately 68% relative to
      As(III)) and DMA ( approximately 75%) but greater than that displayed by As(V) (
      approximately 18%). Analysis of two species of brown algae, Fucus serratus and
      Hizikia fusiforme, by HPLC-HG-ICPMS produced results comparable with those
      obtained from other techniques used in our laboratory (HPLC-ICPMS and LC-ESMS for
      F. serratus) and with results from other laboratories taking part in a round
      robin exercise (H. fusiforme). This study shows for the first time the
      quantitative determination of arsenosugars using the hydride generation method
      without a decomposition step and has considerable implications for analytical
      methods for determining inorganic arsenic based on the formation of volatile
      hydrides.

PMID- 14719894
TI  - Detection of campylobacter and Shigella species in food samples using an array
      biosensor.
AB  - Campylobacter and Shigella bacteria are common causes of food- and water-borne
      illness worldwide. There is a current need in food, medical, environmental, and
      military markets for a rapid and user-friendly method of detecting such
      pathogens. The array biosensor developed at the NRL encompasses these qualities.
      In this study, 25-min, sandwich immunoassays were developed for the detection of
      Campylobacter and Shigella species in both buffer and a variety of food and
      beverage samples. The limit of detection for Shigella dysenteriae in buffer and
      chicken carcass wash was 4.9 x 10(4) cfu mL(-)(1), whereas Campylobacter jejuni
      could be measured at concentrations as low as 9.7 x 10(2) cfu mL(-)(1). The
      limits of detection and dynamic range were found to vary depending on the sample
      matrix, but could be improved by running the sample over the waveguide surface
      for longer periods of time. Samples were run with no preconcentration or
      enrichment steps and little-to-no sample pretreatment prior to analysis.

PMID- 14719895
TI  - Two trace analytical methods for determination of hydroxylated PCBs and other
      halogenated phenolic compounds in eggs from Norwegian birds of prey.
AB  - Two new trace analytical methods are presented for identification and
      quantification of phenolic compounds in complex biological matrixes such as bird
      of prey eggs. One method is based on derivatization with methyl chloroformate
      prior to GC/high-resolution MS (HRMS) analysis in electron impact ionization
      mode. Alternatively, the underivatized phenolic analytes were separated and
      detected by HPLC coupled to time-of-flight MS (TOF-MS) in the negative ion
      electrospray ionization mode. For both methods, the egg samples were homogenized
      and dried with acidified sodium sulfate, cold column-extracted, and cleaned up by
      gel permeation chromatography and subsequently a Florisil column. Recovery rates
      for pentachlorophenol (PCP), tetrabromobisphenol A (TBBPA), and selected
      hydroxylated PCBs (HO-PCBs) from spiked hen's eggs (spiking level 1 ng/g of wet
      weight (ww)) were in the range of 56-98% for the HPLC/MS method and 57-108% for
      GC/MS including derivatization. Typical detection limits of the HPLC/TOF-MS
      method were 5 pg/g ww (1-2 pg injected) for HO-PCBs and PCP and 20 pg/g ww (3 pg
      injected) for TBBPA. The GC/HRMS method achieved detection limits of
      approximately 1 pg/g ww in predatory bird eggs for all analytes (0.2 pg injected
      for derivatized TBBPA and 0.05 pg injected for derivatized HO-PCBs and PCP).
      Eight eggs from four different Norwegian predatory bird species were analyzed.
      The concentrations determined with the two different quantification methods
      corresponded well with each other. PCP and TBBPA were found in all samples at
      concentrations up to 1350 and 13 pg/g ww, respectively (GC/HRMS values). A total
      of 55 penta- to nonachloro-HO-PCB congeners were detected in the eight eggs, 10
      of those could be structurally identified. The maximum HO-PCB congener
      concentration was found for 4-HO-CB 187 in a peregrine falcon egg with estimated
      388 pg/g ww. Another peregrine falcon egg was highest contaminated with sum HO
      PCBs (estimated 2.1 ng/g ww). This level was 1.2 per thousand of the sum PCBs
      value for the same egg. Furthermore, indications were found that the HO-PCB
      congener distribution pattern could be species specific for predatory birds.

PMID- 14719896
TI  - An imprinted organic--inorganic hybrid sorbent for selective separation of
      cadmium from aqueous solution.
AB  - A hierarchical double-imprinting concept was applied to the preparation of a new
      organic-inorganic hybrid sorbent for selective separation of Cd(II) from aqueous
      solution. In the prepared hierarchically imprinted sorbent, both Cd(II) and
      surfactant micelles (cetyltrimethylammonium bromide) were used as templates. The
      sorbent was prepared through self-hydrolysis, self-condensation, and co
      condensation of the cross-linking agent (tetraethoxysilicate) and the functional
      precursor (3-(2-aminoethylamino)-propyltrimethoxysilane) in an alkaline media
      followed by gelation. The selectivity of the sorbent was investigated by a batch
      competitive ion-binding experiment using an aqueous Cd(II) and Zn(II) mixture.
      The largest selectivity coefficient for Cd(II) in the presence of Zn(II) was
      found to be over 100; the largest relative selectivity coefficient between Cd(II)
      and Zn(II), over 200. The uptake capacity of the prepared hierarchically
      imprinted sol-gel sorbent and the selectivity coefficient are much higher than
      those of the sorbent prepared in the absence of CTAB-template. The sorbent
      possesses a fast kinetics for the removal of Cd(II) from aqueous solution.

PMID- 14719898
TI  - Combination of sorption tube sampling and thermal desorption with hollow
      waveguide FT-IR spectroscopy for atmospheric trace gas analysis: determination of
      atmospheric ethene at the lower ppb level.
AB  - The determination of organic trace gases in the ambient environment at the lower
      ppb level is demonstrated based on a novel technique combining sorption tube
      sampling on Molsieve and Carbosieve S-III, thermal desorption, and detection of
      the trace analyte by hollow waveguide Fourier transform infrared (HWG-FT-IR)
      spectroscopy. While ethene concentrations of approximately 5 ppm can be directly
      observed using HWG-FT-IR, enrichment factors of up to 5000 were achieved by
      sorption tube sampling and thermal desorption. Detection limits of approximately
      1 ppb are reported. Efficient enrichment by the sampling tube is achieved due to
      the favorable internal volume ( approximately 0.4 cm(3) at a length of 470 mm) of
      the hollow waveguide serving as a miniaturized gas cell. This new method was
      validated for ethene by thermodesorption-cryofocusing-GC-FID as the reference
      method. Analytical performance has been compared for standard gas mixtures and
      for ethene measurements in urban air. Finally, ethene data from a sampling
      campaign at two alpine sites in Tyrol/Austria are presented.

PMID- 14719897
TI  - Analysis in ultrasmall volumes: microdispensing of picoliter droplets and
      analysis without protection from evaporation.
AB  - A new approach is reported for analysis of ultrasmall volumes. It takes advantage
      of the versatile positioning of a dispenser to shoot approximately 150-pL
      droplets of liquid onto a specific location of a substrate where analysis is
      performed rapidly, in a fraction of the time that it takes for the droplet to
      evaporate. In this report, the site where the liquid is dispensed carries out
      fast-scan cyclic voltammetry (FSCV), although the detection method does not need
      to be restricted to electrochemistry. The FSCV is performed at a microcavity
      having individually addressable gold electrodes, where one serves as working
      electrode and another as counter/pseudoreference electrode. Five or six droplets
      of 10 mM [Ru(NH(3))(6)]Cl(3) in 0.1 M KCl were dispensed and allowed to dry,
      followed by redissolution of the redox species and electrolyte with one or five
      droplets of water and immediate FSCV, demonstrating the ability to easily
      concentrate a sample and the reproducibility of redissolution, respectively.
      Because this approach does not integrate detection with microfluidics on the same
      chip, it simplifies fabrication of devices for analysis of ultrasmall volumes. It
      may be useful for single-step and multistep sample preparation, analyses, and
      bioassays in microarray formats if dispensing and changing of solutions are
      automated. However, care must be taken to avoid factors that affect the aim of
      the dispenser, such as drafts and clogging of the nozzle.

PMID- 14719899
TI  - Analysis of perchlorate in water and soil by electrospray LC/MS/MS.
AB  - A method has been developed for the determination of perchlorate in water and
      soil matrixes using electrospray liquid chromatography/mass spectrometry/mass
      spectrometry. Perchlorate is quantitated by monitoring the ion signal from mass
      83, which is formed by a loss of an oxygen atom from the perchlorate molecular
      ion. The method was developed to be effective and economical in production
      laboratory analysis of perchlorate in environmental water and soil samples. Data
      were gathered to define method sensitivity, performance, selectivity, and
      robustness. Analyte stability, method susceptibility to interferences, and the
      reliability of the chlorine isotope ratio as an identification tool were
      examined. The aqueous method detection limit (MDL) is 0.05 microg/L and was
      determined using an actual groundwater matrix. The soil MDL is 0.5 microg/kg and
      was determined using Ottawa sand. The stability study was performed by spiking
      water samples at 0.25, 10, and 20 microg/L and analyzing them 50 days later.
      Acceptable recoveries were obtained for all samples. The relative standard
      deviation (RSD) for the replicate analyses in the stability study indicates that
      the method is capable of RSD values less than 5% in a relatively clean
      groundwater matrix. The ionization suppression study was performed by spiking
      water samples containing 1000 mg/L carbonate, chloride, and sulfate with 0.05 and
      0.5 microg/L perchlorate and then measuring the recovery of the spike. The
      results indicate that the procedure does not have significant suppression effects
      at the high salt levels tested. Calibration, quality control sample, field
      sample, and suppression study data were combined to examine isotope ratio
      reliability. The results of that work show that chlorine isotope ratios can be
      used to define statistical process control limits for use as an additional
      analyte identification tool.

PMID- 14719900
TI  - Prussian blue based nanoelectrode arrays for H(2)O(2) detection.
AB  - We propose to form nanoelectrode arrays by deposition of the electrocatalyst
      through lyotropic liquid crystalline templates onto inert electrode support.
      Whereas Prussian Blue is known to be a superior electrocatalyst in hydrogen
      peroxide reduction, carbon materials used as electrode support demonstrate only a
      minor activity. We report on the possibility for nanostructuring of Prussian Blue
      by its electrochemical deposition through lyotropic liquid crystalline templates,
      which is noticed from atomic force microscopy images of the resulting surfaces.
      The resulting Prussian Blue based nanoelectrode arrays in flow injection analysis
      mode demonstrate a sub-part-per-billion detection limit (1 x 10(-)(8) M) and a
      linear calibration range starting exactly from the detection limit and extending
      over 6 orders of magnitude of H(2)O(2) concentrations (1 x 10(-)(8) to 1 x 10(
      )(2) M), which are the most advantageous analytical performances in hydrogen
      peroxide electroanalysis.

PMID- 14719901
TI  - Rotation planar chromatography coupled on-line with atmospheric pressure chemical
      ionization mass spectrometry.
AB  - The coupling of a rotation planar preparative thin-layer chromatography system on
      line with mass spectrometry is demonstrated using a simple plumbing scheme and a
      self-aspirating heated nebulizer probe of a corona discharge atmospheric pressure
      chemical ionization source. The self-aspiration of the heated nebulizer delivers
      approximately 20 microL/min of the 3.0 mL/min eluate stream to the mass
      spectrometer, eliminating the need for an external pump in the system. The
      viability of the coupling is demonstrated with a three-dye mixture composed of
      fat red 7B, solvent green 3, and solvent blue 35 separated and eluted from a
      silica gel-coated rotor using toluene. The real-time characterization of the dyes
      eluting from the rotor is illustrated in positive ion full-scan mode. Other self
      aspirating ion source systems including atmospheric pressure photoionization,
      electrospray ionization, and inductively coupled plasma ionization, for example,
      might be configured and used in a similar manner coupled to the chromatograph to
      expand the types of analytes that could be ionized, detected, and characterized
      effectively.

PMID- 14719902
TI  - Transport, location, and quantal release monitoring of single cells on a
      microfluidic device.
AB  - A novel microfluidic device has been developed for on-chip transport, location,
      and quantal release monitoring of single cells. The microfluidic device consists
      of a plate of PDMS containing channels for introducing cells and stimulants and a
      glass substrate into which a cell micro-chamber was etched. The two tightly
      reversibly sealed plates can be separated for respective cleaning, which
      significantly extends the lifetime of the microchip that is frequently clogged in
      cell analysis experiments. Using hydraulic pressure, single cells were
      transported and located on the microfluidic chip. After location of a single PC12
      cell on the microfluidic chip, the cell was stimulated by nicotine that was also
      introduced through the micro-channels, and the quantum release of dopamine from
      the cell was amperometricly detected with our designed carbon fiber
      microelectrode. The results have demonstrated the convenience and efficiency of
      using the microfluidic chip for monitoring of quantal release from single cells
      and have offered a facile method for the analysis of single cells on microfluidic
      devices.

PMID- 14719903
TI  - Detection of point mutation and insertion mutations in DNA using a quartz crystal
      microbalance and MutS, a mismatch binding protein.
AB  - MutS protein is a mismatch binding protein that recognizes mispaired and unpaired
      base(s) in DNA. In this study, we incorporate the MutS protein-based mutation
      recognition into quartz crystal microbalance (QCM) measurements for DNA single
      base substitution mutation and 1-4 base(s) insertion (or deletion) mutation
      detection. The method involves the immobilization of single-stranded probe DNA on
      a QCM surface, the hybridization of target DNA to form homoduplex or heteroduplex
      DNA, and finally the application of MutS protein for the mutation recognition. By
      measuring the MutS binding signal, DNA containing a T:G mismatch or unpaired
      base(s) is(are) discriminated against perfectly matched DNA at target
      concentrations ranging from 1nM to 5 microM. Furthermore, the QCM damping
      behavior upon MutS-DNA complex formation is studied using a Network Analyzer. The
      measured motional resistance changes per coupled MutS unit mass (deltaR/deltaf)
      are found to be indicative of the viscoelastic or structural properties of the
      bound protein, corresponding to different binding mechanisms. In addition, the
      deltaR/deltaf values vary remarkably when the MutS protein binds at different
      distances away from the QCM surface. Thus, these values can be used as a
      "fingerprint" for MutS mismatch recognition and also used to quantitatively
      locate the mutation site.

PMID- 14719904
TI  - Homogeneous detection of single rolling circle replication products.
AB  - We describe a simple and straightforward approach for homogeneous and isothermal
      detection of individual rolling circle replication (RCR) products, which
      represent individual padlock probe circularization events. The RCR products
      constitute tens of kilobases long single-stranded tandem repeated copies of the
      probe sequence, and in solution, they fold into micrometer-sized random coils.
      The method is based on the local enrichment of fluorescence-labeled probes that
      hybridize to the coiled RCR products compared to the concentration of free probes
      in solution. We present a detailed characterization of the fluorescence-labeled
      products using a highly sensitive and fast microscopy setup. At a 10(4)-fold
      excess of free label, we were able to detect and follow individual RCR products
      at a signal-to-background noise ratio of 27. This high signal-to-background noise
      ratio leaves room for analysis in a simple detection device at higher speeds or
      at lower labeling ratios.

PMID- 14719905
TI  - Quantitative photoelectrochemical detection of biological affinity reaction:
      biotin-avidin interaction.
AB  - Quantitative detection of a biological affinity reaction, the biotin/avidin
      recognition, was achieved using our newly developed photoelectrochemical
      analytical system. The system is based on the operation mechanism of the well
      developed dye-sensitized photoelectrochemical solar cells and comprises a
      ruthenium tris(2,2'-bipyridine) (Ru-bipy) derivative as the photoelectrochemical
      signal-generating molecule, oxalate as the sacrificial electron donor, and tin
      oxide nanoparticle as the semiconductor electrode material. To perform the
      affinity reaction, avidin was immobilized on SnO(2) electrode by passive
      adsorption. Biotin-linked bovine serum albumin (BSA) was labeled with an NHS
      ester derivative of Ru-bipy. After binding of BSA to the surface-immobilized
      avidin through biotin, photoelectrochemical measurement was carried out in the
      presence of oxalate. Anodic photocurrent was turned on and off repeatedly by
      control of incidental light. The action spectrum of the photocurrent resembled
      the absorption spectrum of Ru-bipy, proving the photocurrent was generated from
      the metal complex. A linear relationship between photocurrent and BSA
      concentration was obtained in the range of 1-100 microg/mL. This is the first
      case of quantitative photoelectrochemical detection of a biological affinity
      interaction.

PMID- 14719906
TI  - Dedifferentiation of lineage-committed cells by a small molecule.
AB  - Combinatorial libraries were screened for molecules that induce mouse myogenic
      lineage committed cells to dedifferentiate in vitro. A 2,6-disubstituted purine,
      reversine, was discovered that induces lineage reversal of C2C12 cells to become
      multipotent progenitor cells which can redifferentiate into osteoblasts and
      adipocytes. This and other such molecules are likely to provide new insights into
      the molecular mechanisms that control cellular dedifferentiation and may
      ultimately be useful to in vivo stem cell biology and therapy.

PMID- 14719907
TI  - Controlled functionalization of multiwalled carbon nanotubes by in situ atom
      transfer radical polymerization.
AB  - The in situ ATRP (atom transfer radical polymerization) "grafting from" approach
      was successfully applied to graft poly(methyl methacrylate) (PMMA) onto the
      convex surfaces of multiwalled carbon nanotubes (MWNT). The thickness of the
      coated polymer layers can be conveniently controlled by the feed ratio of MMA to
      preliminarily functionalized MWNT (MWNT-Br). The resulting MWNT-based polymer
      brushes were characterized and confirmed with FTIR, 1H NMR, SEM, TEM, and TGA.
      Moreover, the approach has been extended to the copolymerization system,
      affording novel hybrid core-shell nanoobjects with MWNT as the core and
      amphiphilic poly(methyl methacrylate)-block-poly(hydroxyethyl methacrylate) (PMMA
      b-PHEMA) as the shell. The approach presented here may open an avenue for
      exploring and preparing novel carbon nanotubes-based nanomaterials and molecular
      devices with tailor-made structure, architecture, and properties.

PMID- 14719908
TI  - Rearrangement of a 2-methylenecyclobutanone derivative triggered by photoinduced
      electron transfer: an unprecedented oxa analogue of the tetramethyleneethane
      radical cation.
AB  - On irradiation of p-chloranil (CA), 2,2-bis(p-methoxyphenyl)-3,3-dimethyl-4
      methylenecyclobutanone (1) gives 2,2-bis(p-methoxyphenyl)-4
      isopropylidenecyclobutanone (2), whereas 2 affords a CA adduct (4), suggesting
      that a novel rearrangement of 1 to give 2 occurs irreversibly via intermediate
      3*+, a radical cation variant of an unprecedented oxa analogue of
      tetramethyleneethane.

PMID- 14719909
TI  - A nucleobase that releases reporter tags upon DNA oxidation.
AB  - We have developed a novel nucleosbase, edaG, that efficiently releases various
      reporter units upon one-electron oxidation. The edaG-selective degradation of
      ODNs was achieved by various mild oxidizing agents. The oxidant-dependent
      molecular releasing technique is quite useful not only for DNA-based drug
      releasing systems but also for the detection of long-range hole transport through
      DNA without time-consuming analysis.

PMID- 14719910
TI  - DNA-templated self-assembly of protein and nanoparticle linear arrays.
AB  - Self-assembling DNA tiling lattices represent a versatile system for nanoscale
      construction. Self-assembled DNA arrays provide an excellent template for
      spatially positioning other molecules with increased relative precision and
      programmability. Here we report an experiment using a linear array of DNA triple
      crossover tiles to controllably template the self-assembly of single-layer or
      double-layer linear arrays of streptavidin molecules and streptavidin-conjugated
      nanogold particles through biotin-streptavidin interaction. The organization of
      streptavidin and its conjugated gold nanoparticles into periodic arrays was
      visualized by atomic force microscopy and scanning electron microscopy.

PMID- 14719911
TI  - A tetranuclear 3d-4f single molecule magnet: [CuIILTbIII(hfac)2]2.
AB  - We report now the first single molecule magnet (SMM) consisting of d-f elements.
      The present study demonstrates that the synthesis of the d-f polynuclear molecule
      is a very promising approach to SMMs. (1) The d-f polynuclear molecule can be
      easily synthesized by the assembly reaction of the d-component and the f
      component, (2) the high-spin ground state can be generated by a smaller number of
      metal ions than the d complex, and (3) the molecular magnetic anisotropy is
      easily derived from the f-component.

PMID- 14719912
TI  - Dynamics of density fluctuation of supercritical fluid mapped on phase diagram.
AB  - A time evolution of polar molecules inhomogeneously dispersing in mesoscale is
      investigated by dynamic light scattering around the gas-liquid critical point.
      The dynamics evaluated on phase diagrams produces a contour map of critical
      slowing down and suggests a ridge to be a trace of intermediate lines between gas
      and liquid states. A good coincidence between dynamics and static inhomogeneities
      is confirmed in the wide density, and it is consistent with theoretical
      expressions.

PMID- 14719913
TI  - A new solvent system for recycling catalysts for chelation-assisted
      hydroacylation of olefins with primary alcohols.
AB  - A new method to separate and reuse the catalyst system consisting of a rhodium
      complex and 2-aminopyridines for chelation-assisted hydroacylation was achieved
      using phenol and 4,4'-dipyridyl as the reaction medium, and 4
      diphenylphosphinobenzoic acid as a ligand.

PMID- 14719914
TI  - Infrared electronic absorption in a single-component molecular metal.
AB  - The infrared spectra of the crystal of transition metal complex molecules with
      extended-TTF ligands, Ni(tmdt)2, which is the first single-component molecular
      metal that has a stable metallic state even at low temperatures, exhibited an
      extremely low-energy electronic absorption around 2200 cm-1 (tmdt =
      trimethylenetetrathiafulvalenedithiolate). The systematic shift of the absorption
      peaks for molecules similar to Ni(tmdt)2, which range from metallic to
      semiconducting crystals, shows that the single-component molecular conductors are
      composed of molecules with unprecedentedly small HOMO-LUMO gaps.

PMID- 14719915
TI  - Enantioselective crystal growth of leucine on a self-assembled monolayer with
      covalently attached leucine molecules.
AB  - Enantioselective crystal growth of leucine occurs on a solid surface modified
      with a self-assembled monolayer depending on the chirality of the enantiomer
      attached, as evidenced by the X-ray diffraction method.

PMID- 14719916
TI  - Antiaromaticity in bare deltahedral silicon clusters satisfying Wade's and
      Hirsch's rules: an apparent correlation of antiaromaticity with high symmetry.
AB  - Entirely unlike the aromatic closo BnHn2- borane dianions, isoelectronic Si62-
      and Si122- are antiaromatic. Their Oh and Ih symmetries are responsible, as the
      other deltahedral silicon dianion clusters do not exhibit this behavior. These
      high symmetries prevent mixing among the degenerate lone pair and skeletal
      orbitals, leading to paratropic behavior.

PMID- 14719917
TI  - Stacking of molecules possessing a fullerene apex and a cup-shaped cavity
      connected by a silicon connection.
AB  - Hexagonal or tetragonal packing of columnar stacks in crystals and liquid
      crystals has been observed for a series of molecules possessing a fullerene apex
      and an aromatic cone that are connected with a Si-C connection. The columnar
      stacking of the new shuttlecock molecules is constitutionally stable but
      conformationally flexible due to the large cavity created on the top of the
      fullerene molecule.

PMID- 14719918
TI  - Ab initio interaction energies of hydrogen-bonded amino acid side
      chain[bond]nucleic acid base interactions.
AB  - Hydrogen-bonding interactions often make substantial contributions to the
      specificity of protein-nucleic acid complexes. Using a geometric modeling
      approach, we previously identified 28 possible doubly hydrogen-bonded
      interactions to the four unpaired RNA bases. Here we present interaction energies
      of these models, calculated by ab initio quantum chemical methods, and describe a
      correlation between the computed energies and observed frequencies of the
      interactions. In general, interactions with charged side chains show the most
      favorable energies. An Asp/Glu-G interaction may be especially favorable for
      recognition of unpaired guanines in RNAs. Asn and Ser/Thr/Tyr side chains are
      calculated to make iso-energetic interactions to the Hoogsteen face of adenine,
      but Asn-A interactions are much more common with DNA than RNA, and Ser/Thr/Tyr-A
      interactions are more common with RNA than DNA. Examination of the known
      interactions suggests that Ser/Thr/Tyr may be accommodated in a wider variety of
      protein contexts at RNA-protein interfaces. With these calculated intrinsic
      affinities, it should be possible to better assess the contributions of bidentate
      hydrogen-bonding interactions to RNA- and DNA-binding specificity.

PMID- 14719919
TI  - Hybridization of modified-heme reconstitution and distal histidine mutation to
      functionalize sperm whale myoglobin.
AB  - To modulate the physiological function of a hemoprotein, most approaches have
      been demonstrated by site-directed mutagenesis. Replacement of the native heme
      with an artificial prosthetic group is another way to modify a hemoprotein.
      However, an alternate method, mutation or heme reconstitution, does not always
      demonstrate sufficient improvement compared with the native heme enzyme. In the
      present study, to convert a simple oxygen storage hemoprotein, myoglobin, into an
      active peroxidase, we applied both methods at the same time. The native heme of
      myoglobin was replaced with a chemically modified heme 2 having two aromatic
      rings at the heme-propionate termini. The constructed myoglobins were examined
      for 2-methoxyphenol (guaiacol) oxidation in the presence of H2O2. Compared with
      native myoglobin, rMb(H64D.2) showed a 430-fold higher kcat/Km value, which is
      significantly higher than that of cytochrome c peroxidase and only 3-fold less
      than that of horseradish peroxidase. In addition, myoglobin-catalyzed degradation
      of bisphenol A was examined by HPLC analysis. The rMb(H64D.2) showed drastic
      acceleration (>35-fold) of bisphenol A degradation compared with the native
      myoglobin. In this system, a highly oxidized heme reactive species is smoothly
      generated and a substrate is effectively bound in the heme pocket, while native
      myoglobin only reversibly binds dioxygen. The present results indicate that the
      combination of a modified-heme reconstitution and an amino acid mutation should
      offer interesting perspectives toward developing a useful biomolecule catalyst
      from a hemoprotein.

PMID- 14719921
TI  - Nondissociative chemisorption of methanethiol on Ag(110): a critical result for
      self-assembled monolayers.
AB  - Three definitive experiments have been performed to investigate the possibility
      of dissociative adsorption of methanethiol (CH3SH) on clean Ag(110). On the clean
      Ag(110) surface, the adsorption in the first layer occurs to 0.5 ML, producing a
      (2 x 1) low-energy electron diffraction (LEED) structure. The undissociated
      molecule desorbs starting at approximately 140 K, and only tiny quantities of
      other gaseous products are desorbed, and only tiny quantities of S-containing
      species remain. Using a 50:50% mixture of CH3SD and CD3SH, we find no evidence of
      S-H or S-D bond scission between these molecules upon desorption. And finally,
      when the CH3SH molecule is incident on the clean Ag(110) surface in the
      temperature range of 230-400 K, less than 1% of the incident molecules dissociate
      to produce adsorbed sulfur-containing species. The results influence our thinking
      about the surface bonding of alkanethiol-based self-assembled monolayers (SAMs)
      on noble metals.

PMID- 14719920
TI  - Visual detection of cysteine and homocysteine.
AB  - The determination of cysteine and homocysteine levels is of great current
      interest for the monitoring of desease states. A new colorimetric method for the
      simultaneous detection of l-cysteine and l-homocysteine has been developed. A
      fluorescein derivative reacts with the above amino acids, producing their
      respective thiazolidines resulting in color changes. Interference from other
      amino acids and proteins is minimal.

PMID- 14719922
TI  - Mechanism of Ru(II)-catalyzed olefin insertion and C-H activation from quantum
      chemical studies.
AB  - The mechanism of catalytic hydroarylation of olefins by the homogeneous
      Ru(Tp)(CO)(Ph)(NCCH3) catalyst recently reported by Gunnoe et al. is
      characterized using quantum mechanics (density functional theory). The catalytic
      cycle features two key steps, 1,2-olefin insertion and C-H activation via an
      unusual mechanism, oxidative hydrogen migration. We find that these two key steps
      are competitive and that improving the rate of one step is detrimental to the
      rate of the other. The Ru catalyst has better balance and consequently higher
      activity than the previously explored Ir-based system.

PMID- 14719923
TI  - Multicomponent reactions are accelerated in water.
AB  - Two multicomponent reactions, the Ugi and Passerini reactions, are accelerated by
      the use of aqueous solutions. The rate enhancements compared to those by organic
      solvents can approach 300-fold. Reactions performed in water offer another
      advantage that products are often insoluble, permitting direct isolation by
      precipitation. The methods were applied to the preparation of three small
      combinatorial libraries.

PMID- 14719924
TI  - High-resolution NMR spectra in inhomogeneous fields via IDEAL (intermolecular
      dipolar-interaction enhanced all lines) method.
AB  - Intermolecular double-quantum technique is used to yield high-resolution NMR
      spectra in inhomogeneous magnetic fields. The method exploits the distant dipolar
      interactions between the solvent and solute nuclear spins. Chemical shifts, J
      couplings, multiplicity patterns, and relative areas are retained with the
      method. Except for a 1.5-fold change in the scale factor of J couplings, other
      parameters are consistent with those extracted from one-dimensional spectra
      obtained in a homogeneous field.

PMID- 14719926
TI  - Catalytic asymmetric intramolecular alpha-alkylation of aldehydes.
AB  - The development of a general catalytic asymmetric aldehyde alpha-alkylation
      reaction constitutes a major challenge in organic synthesis. Here, we report the
      first and successful approach toward its solution: (S)-alpha-methyl proline
      catalyzes the intramolecular alkylation of various halo aldehydes to the
      corresponding formyl cyclopentanes, -cyclopropanes, or -pyrrolidines in excellent
      yields and enantioselectivities. Most remarkably, racemization, aldolization, or
      catalyst alkylation do not occur to any significant extend, further illustrating
      the power, mildness, and profound selectivity of enamine catalysis.

PMID- 14719925
TI  - Enzymatic synthesis of phosphoroselenoate DNA using thymidine 5'-(alpha-P
      seleno)triphosphate and DNA polymerase for X-ray crystallography via MAD.
AB  - We report here the first study of enzymatic synthesis of two phosphoroselenoate
      (PSe) DNAs using the two alpha-Se-TTP diastereomers (Sp and Rp) and DNA
      polymerase. The experimental results indicate that Klenow equally recognizes the
      two individual diastereomers at the same level as natural TTP. The incorporations
      of the PSe groups at the expected sites have been confirmed by the digestion
      resistance to exonuclease III, and the different patterns of the digestion
      resistance of DNA I and II indicate the configurational differences of the PSe
      centers (Sp or Rp). Unlike chemical synthesis, which is limited to short DNAs and
      where the separation of the PSe DNA diastereomers is necessary, this enzymatic
      method can be used to prepare longer DNAs without diastereomer separation. This
      quantitative enzymatic approach is particular valuable for the synthesis of
      longer DNAs with multiple PSe groups in large scale for their X-ray crystal
      structure determination by the MAD phasing technique.

PMID- 14719927
TI  - Hyperconjugative and inductive perturbations in poly(p-phenylene vinylenes).
AB  - New polymers having high solid-state fluorescence quantum yields and the ability
      to tune their electron affinity without effecting their band gap using
      hyperconjugative interactions is reported. The novel three-dimensional
      poly(phenylene vinylenes) having [2.2.2] bicyclic ring systems shown were
      synthesized, and the different hyperconjugative perturbations provide
      differential fluorescence sensory quenching responses to electron-rich and
      electron-deficient analytes in solution and solid thin films.

PMID- 14719928
TI  - Reduction of dinitrogen to planar bimetallic M2(mu-eta 2:eta 2-N2) complexes of
      Y, Ho, Tm, and Lu using the K/Ln[N(SiMe3)2]3 reduction system.
AB  - The reaction of Ln[N(SiMe3)2]3 with K under N2 in THF forms the dinitrogen
      complexes {[(Me3Si)2N]2(THF)Ln}2(mu-eta2:eta2-N2) (Ln = Y, Ho, Tm, and Lu)
      previously available only for lanthanides with highly reducing divalent states,
      that is, Tm, Dy, and Nd. The Y and Lu complexes are the first diamagnetic
      complexes of this type. The Ln2N2 moiety is planar, and the 1.268(3) and 1.285(4)
      A NN distances in these complexes are consistent with the presence of (N2)2-.

PMID- 14719929
TI  - Chiral copper complexes of phosphino sulfenyl ferrocenes as efficient catalysts
      for enantioselective formal Aza Diels-Alder reactions of N-sulfonyl imines.
AB  - In the presence of a catalytic amount of silver perchlorate, copper(I) bromide
      complexes of planar chiral 1-phosphino-2-sulfenylferrocenes behave as very
      efficient chiral Lewis acids catalysts in the formal Aza Diels-Alder reaction of
      N-arylsulfonyl aldimines with electron-rich dienes (Danishefsky's and related
      dienes). Mixing of equimolar amounts of the readily available enantiopure
      ferrocenyl P,S-bidentate ligand and CuBr quantitatively affords the precatalyst
      Cu complex as an air-stable solid. This catalytic asymmetric procedure has a
      broad structural scope: aldimines of aromatic, alpha,beta-unsaturated, and even
      enolizable aliphatic aldehydes have been successfully used. The corresponding 2,3
      dihydro-4-pyridones were obtained in good yields (57-90%) and with homogeneously
      high enantioselectivity (82-97% ee).

PMID- 14719930
TI  - The sulfur chemistry of shiitake mushroom.
AB  - Allium herbs, such as Chinese chive, garlic, and onion, share a common sulfur
      biochemistry that occurs on cell breakage. Sulfoxide precursors are converted
      enzymatically to sulfenic acid intermediates and thence to a variety of pungent
      and in some cases noxious sulfur species that probably act to deter herbivores.
      Very similar biochemistry has been proposed to occur in shiitake mushrooms. Prior
      to the present work, our understanding of the sulfur biochemistry of these plants
      and fungi has been derived largely from conventional analysis procedures. We have
      used in situ sulfur K-edge X-ray absorption spectroscopy in intact and disrupted
      allium plants and shiitake mushroom. The expected changes in sulfur forms
      following cell breakage are indeed observed for the alliums, but no significant
      changes occur for the fungus. Thus, any changes involving the sulfur-containing
      compounds of shiitake mushroom following cell breakage occur to a far smaller
      extent than those involving allium plants, presumably reflecting the need in
      shiitake for action by multiple enzymes, namely a gamma-glutamyl transpeptidase
      and a C-S lyase. The shiitake C-S lyase occurs in far lower concentrations than
      the corresponding enzyme in garlic. Furthermore, cleavage of the flavorant
      precursor by the shiitake C-S lyase is reported to cease before cleavage of the
      precursor has been completed, presumably due to a product or suicide inhibition
      mechanism.

PMID- 14719932
TI  - Synthesis of silica nanoparticles having a well-ordered mesostructure using a
      double surfactant system.
AB  - A well-ordered hexagonal structure of the mesopores was produced by previous
      hydrolysis of tetraethoxysilane with hydrochloric acid and subsequent assembly of
      cationic surfactant micelles and anionic silicate species at a basic condition.
      Mesoporous silica nanoparticles (20-50 nm) having a well-ordered hexagonal
      mesostructure were produced using a mixture of cationic surfactant as a template
      and nonionic block copolymer as a suppressant of grain growth.

PMID- 14719931
TI  - Expression, reconstitution, and mutation of recombinant Streptomycescoelicolor
      NiSOD.
AB  - Nickel-dependent superoxide dismutases (NiSODs) represent a novel solution to
      controlling the deleterious effects of reactive oxygen species derived from
      superoxide in biology. The expression of recombinant Streptomyces coelicolor
      NiSOD and its in vitro processing and reconstitution to yield fully active enzyme
      is reported. The results of studies of NiSODs involving mutations in two putative
      nickel binding ligands are also reported. These studies show that mutation of
      M28, a strictly conserved residue and one of only three S-donor ligands in the
      enzyme, has no measurable effect on the spectroscopic or catalytic properties of
      the enzyme. In contrast, mutation of the strictly conserved N-terminal H residue
      has dramatic effects on both the spectroscopic and catalytic properties. These
      results provide insights into structural and mechanistic aspects of the novel
      nickel-containing reactive site.

PMID- 14719933
TI  - 13C-13C NOESY: an attractive alternative for studying large macromolecules.
AB  - 13C direct detection provides a valuable alternative to 1H detection to overcome
      fast relaxation because of its smaller magnetic moment. 13C-13C NOESY spectra
      were acquired for a dimeric protein of molecular mass 32 000 and for a monomeric
      analogue. With increasing molecular mass, the quality of 13C-13C NOESY spectra
      improves while the scalar-based experiments become less sensitive, as predicted
      by the increase in the molecular mass. 13C-13C NOESY spectra of the dimer were
      acquired with different mixing times. The mixing time can be tuned to detect
      mainly one-bond correlations, or it can be increased to also detect correlations
      between nuclei at longer distances. It is proposed that 13C-13C dipolar-based
      experiments provide a promising tool for signal detection and assignment in large
      macromolecules, such as multimeric species and macromolecular complexes, for
      which scalar-based experiments become less effective.

PMID- 14719934
TI  - One-pot synthesis of nitrogen heterocycles initiated by regio- and
      diastereoselective carbon-carbon bond formation of bifunctional carbonyl
      compounds.
AB  - We report a one-pot synthesis of nitrogen heterocyclic compounds initiated by the
      allylation of the formyl group of bifunctional carbonyl compounds accompanying
      chemo-, regio-, and diastereoselective carbon-carbon bond formation in side chain
      moieties.

PMID- 14719935
TI  - Palladium-catalyzed multicomponent coupling of alkynes, imines, and acid
      chlorides: a direct and modular approach to pyrrole synthesis.
AB  - A new palladium-catalyzed method to prepare pyrroles directly from three basic
      building blocks-imines, alkynes, and acid chlorides-is described. This approach
      provides a straightforward method both to prepare pyrroles in one step and to
      diversify their structure by simple variation of any of the three starting
      materials. Mechanistic studies suggest that this process occurs via a complex
      series of eight individual steps, and this is discussed.

PMID- 14719936
TI  - New Fischer carbene complexes of rhodium(i): preparation and 2-cyclopentenone
      ring synthesis by annelation to alkynes.
AB  - A new type of metal carbene complexes of group 9, specifically a cationic Fischer
      carbene of rhodium(I), has been synthesized from chromium carbene complexes via
      double transfer of carbene and CO ligands. These complexes reveal a different
      reactivity than other transition metal carbenes, including their chromium
      precursors, toward neutral and electron-poor alkynes, giving selectively
      polysubstituted cyclopentenones.

PMID- 14719938
TI  - Palladium pincer complex-catalyzed trimethyltin substitution of functionalized
      propargylic substrates. An efficient route to propargyl- and allenyl-stannanes.
AB  - Palladium pincer complex-catalyzed reaction of functionalized propargyl chloride
      (and mesylate) derivatives with hexamethylditin gives allenyl- and propargyl
      stannane products. This catalytic activity is in sharp contrast with the
      reactivity of commonly used palladium(0) catalysts inducing addition of
      hexamethylditin to the triple bond. The product distribution of the pincer
      complex-catalyzed reaction is controlled by the substituent effects of the
      propargylic substrate: electron-withdrawing functionalities give mainly allenyl
      stannane products, while with electron-donating groups the main product is
      propargyl stannane. The catalytic reaction proceeds under very mild conditions
      tolerating many functionalities such as OH, OAc, NR3, and NR2Ac groups. Our
      mechanistic studies indicate that the key intermediate of the reaction is a
      monotrimethylstannane palladium pincer complex. A remarkable feature of the
      studied catalytic process is that the palladium catalyst does not undergo redox
      reactions, but its oxidation state is restricted to palladium(II). Since
      palladium(0) intermediates does not occur in this process, the catalyst is very
      stable and highly chemoselective.

PMID- 14719937
TI  - Nonheme FeIVO complexes that can oxidize the C-H bonds of cyclohexane at room
      temperature.
AB  - Nonheme oxoiron(IV) complexes of two pentadentate ligands, N4Py (N,N-bis(2
      pyridylmethyl)-bis(2-pyridyl)methylamine) and Bn-tpen (N-benzyl-N,N',N'-tris(2
      pyridylmethyl)-1,2-diaminoethane), have been generated and found to have
      spectroscopic properties similar to the closely related tetradentate TPA (tris(2
      pyridylmethyl)amine) complex reported earlier. However, unlike the TPA complex,
      the pentadentate complexes have a considerable lifetime at room temperature. This
      greater thermal stability has allowed the hydroxylation of alkanes with C-H bonds
      as strong as 99.3 kcal/mol to be observed at room temperature. Furthermore, a
      large deuterium KIE value is found in the oxidation of ethylbenzene. These
      observations lend strong credence to postulated mechanisms of mononuclear nonheme
      iron enzymes that invoke the intermediacy of oxoiron(IV) species.

PMID- 14719939
TI  - Synthesis of heparin oligosaccharides.
AB  - An efficient preparation of rare 2-O-benzoyl-3-O-benzyl-1,6-anhydro-beta-l
      idopyranose from commercially available diacetone alpha-d-glucose in five
      straightforward steps is described here. With this key building block in hand,
      the total syntheses of heparin oligosaccharides with three, five, seven, and nine
      sugar units are successfully carried out.

PMID- 14719940
TI  - Highly electrophilic (salen)ruthenium(VI) nitrido complexes.
AB  - A series of cationic ruthenium(VI) nitrido species containing the cyclohexyl
      bridged salen ligand (L) and its derivatives, [RuVI(N)(L)]+, have been prepared
      by treatment of [NBun4][RuVI(N)Cl4] with H2L in methanol. The structure of
      [RuVI(N)(L)](ClO4) (1a) has been determined by X-ray crystallography, d(RuN) =
      1.592 A. In solvents such as DMF or DMSO, [RuVI(N)(L)]+ undergoes a facile N...N
      coupling reaction at room temperature to produce N2 and [RuIII(L)(S)2]+ (S =
      solvent). 1a reacts rapidly with secondary amines to produce diamagnetic RuIV
      hydrazido(1-) species, [RuIV(N(H)NR2)(L)(HNR2)]+. The reaction with morpholine is
      first order in RuVI and second order in morpholine with k(CH3CN, 25 degrees C) =
      2.08 x 106 M-2 s-1. This rate constant is over 4 orders of magnitude larger than
      that of the corresponding reaction of the electrophilic osmium nitride, trans
      [OsVI(N)(tpy)(Cl)2]+, with morpholine. The structure of
      [Ru(NHNC4H8)(L)(NHC4H8)](PF6)2 has been determined by X-ray crystallography, the
      Ru-N(hydrazido) distance is 1.940 A, and the Ru-N-N angle is 129.4 degrees .

PMID- 14719941
TI  - Imidazolium ion-terminated self-assembled monolayers on Au: effects of
      counteranions on surface wettability.
AB  - Self-assembled monolayers presenting imidazolium ions at the tail ends (SAMIMs)
      having different counteranions have been prepared on Au, and the measurement of
      water contact angles of the surfaces proved to be an extremely valuable simple
      technique for quantifying the effects of counteranions on hydrophilicity and
      hydrophobicity of SAMIMs, which will be extrapolated to the water miscibility of
      the related ionic liquids.

PMID- 14719942
TI  - In situ FTIR-ATR analysis and titration of carboxylic acid-terminated SAMs.
AB  - FTIR-ATR measurements permit detailed structural analysis and in situ titration
      of carboxylate-terminated self-assembled monolayers. Both monomeric and
      dimeric/oligomeric acid groups are seen, and their acid-base behavior is directly
      monitored. Monomers that are hydrogen bonded only to surrounding water molecules
      have a pKa = 4.9, while the pKa for the aggregated molecules is 9.3.

PMID- 14719943
TI  - Characterization of a kinetically stable, highly ordered, octameric form of
      lithium tert-butoxide and its implications regarding aggregate formation.
AB  - The controlled reaction of molecular oxygen with hydrocarbon solutions of tBuLi
      results in the unexpected formation of the octameric species [(tBuOLi)8], 18.
      Single-crystal X-ray diffraction studies indicate that the connectivity within 18
      corresponds with the fusion of two face-opened tetrameric cubanes. Cryoscopic
      studies establish the stability of the octamer in benzene solution, but heating
      results in aggregate rearrangement to the commonly found prismatic hexameric
      form, 16. Theoretical calculations confirm that the hexameric form is the
      thermodynamically favored aggregate.

PMID- 14719944
TI  - Quantum-chemical calculations for paramagnetic 13C NMR chemical shifts of iron
      bound cyanide ions of iron porphyrins in ground and low-lying excited states
      containing ferric (dxy)2(dxz,yz)3 and (dxy)1(dxz,yz)4 configurations.
AB  - Accurate quantum-chemical calculations were carried out for bis(cyanide) and
      cyanide-imidazole Fe(III) porphyrins in the ground and low-lying excited states
      including both the ferric (dxy)2(dxz,yz)3 and (dxy)1(dxz,yz)4 configurations. The
      trans-ligand effect on the paramagnetic 13C NMR chemical shifts of the iron-bound
      13CN- was well reproduced by the present calculations. Further, in
      bis(cyanide)(meso-tetraethyl) Fe(III) porphyrin, which has a ruffled porphyrin
      ring, the (dxy)1(dxz,yz)4 configuration is included in the ground state, and the
      alternative (dxy)2(dxz,yz)3 configuration is located closely in energy to the
      ground state. Ruffling of porphyrin rings extremely affects the 13C chemical
      shift of iron-bound CN in the (dxy)1(dxz,yz)4 configuration but not in the
      (dxy)2(dxz,yz)3 configuration.

PMID- 14719945
TI  - Enantiospecific electrodeposition of chiral CuO films on single-crystal Cu(111).
AB  - Epitaxial films of monoclinic CuO have been electrodeposited on single-crystal
      Cu(111) from solutions containing either (S,S)- or (R,R)-tartrate. X-ray pole
      figure analysis reveals that the CuO film grown from (S,S)-tartrate exhibits a
      (1) out-of-plane orientation while the film grown from (R,R)-tartrate has a (11)
      orientation. Even though CuO does not crystallize within a chiral space group,
      the orientations obtained exhibit a surface chirality similar to that obtained
      from high index fcc metal surfaces. The films were shown to be enantioselective
      toward the catalytic oxidation of tartrate molecules by cyclic voltammetry. The
      technique should prove to be applicable to the electrodeposition of chiral
      surfaces of other low-symmetry materials on achiral substrates and should prove
      to be of use to those interested in the synthesis, separation, and detection of
      chiral molecules.

PMID- 14719946
TI  - Coupling a natural receptor protein with an artificial receptor to afford a
      semisynthetic fluorescent biosensor.
AB  - An artificial receptor and a signal transducer have been engineered on a lectin
      (saccharide-binding protein) surface by a post-photoaffinity labeling
      modification method. Saccharide binding can be directly and selectively read out
      by the fluorescence changes of the fluorophore via photoinduced electron transfer
      (PET) mode. Fluorescence titration with various saccharides reveals that
      molecular recognition by the artificial receptor is successfully coupled to the
      native binding site of the lectin, producing a novel fluorescent saccharide
      biosensor showing modulated specificity and enhanced affinity. Designed
      cooperativity between artificial and native molecular recognition modules was
      quantitatively demonstrated by the comparison of the binding affinities, and it
      represents a new strategy in molecular recognition. By using appropriate
      artificial receptors and various native lectins, this approach may provide many
      new semisynthetic biosensors for saccharide derivatives such as glycolipids and
      glycopeptides/proteins. An extended library of lectin-based biosensors is
      envisioned to be useful for glycome research, a newly emerging field of the post
      genomic era.

PMID- 14719947
TI  - Protein-template-driven formation of polynuclear iron species.
AB  - Ferritins are iron-storage proteins capable of holding up to 4500 Fe(3+) ions
      within a single water-soluble protein shell made from 24 polypeptide chains. The
      Glu128Arg/Glu135Arg mutants of Escherichia coli and Rhodobacter capsulatus
      bacterioferritins are unable to associate into 24-meric structures, with dimers
      of polypeptide chains being their stable forms. The aerobic addition to these of
      up to 8-10 or 14-20 Fe(2+) ions per dimer, respectively, results in the oxidation
      of the added Fe(2+) to Fe(3+). Gel permeation chromatography and sedimentation
      equilibrium studies confirm that the Fe(3+) ions are associated with the
      polypeptide dimer, and the lack of intense EPR signals from magnetically isolated
      Fe(3+) ions confirms the formation of one or more antiferromagnetically coupled
      clusters of Fe(3+) ions. The effect of Fe(3+) chelators on iron-loaded subunit
      dimers is to remove the Fe(3+) from the protein, but to do so slowly, consistent
      with it not being merely adventitiously associated with protein. These data
      provide experimental support for the presence of nucleation centers for the
      mineral cores in bacterioferritins and indicate that these proteins are not
      simply acting as vessels in which hydrolysis of Fe(3+) occurs independent from
      the protein surface. From analyses of X-ray structures and amino acid sequence
      comparisons, possible nucleation sites are identified.

PMID- 14719948
TI  - Comparison between the geometric and electronic structures and reactivities of
      [FeNO]7 and [FeO2]8 complexes: a density functional theory study.
AB  - In a previous study, we analyzed the electronic structure of S = 3/2 [FeNO](7)
      model complexes [Brown et al. J. Am. Chem. Soc. 1995, 117, 715-732]. The combined
      spectroscopic data and SCF-X alpha-SW electronic structure calculations are best
      described in terms of Fe(III) (S = 5/2) antiferromagnetically coupled to NO(-) (S
      = 1). Many nitrosyl derivatives of non-heme iron enzymes have spectroscopic
      properties similar to those of these model complexes. These NO derivatives can
      serve as stable analogues of highly labile oxygen intermediates. It is thus
      essential to establish a reliable density functional theory (DFT) methodology for
      the geometry and energetics of [FeNO](7) complexes, based on detailed
      experimental data. This methodology can then be extended to the study of
      [FeO(2)](8) complexes, followed by investigations into the reaction mechanisms of
      non-heme iron enzymes. Here, we have used the model complex
      Fe(Me(3)TACN)(NO)(N(3))(2) as an experimental marker and determined that a pure
      density functional BP86 with 10% hybrid character and a mixed triple-zeta/double
      zeta basis set lead to agreement between experimental and computational data.
      This methodology is then applied to optimize the hypothetical
      Fe(Me(3)TACN)(O(2))(N(3))(2) complex, where the NO moiety is replaced by O(2).
      The main geometric differences are an elongated Fe[bond]O(2) and a steeper
      Fe[bond]O[bond]O angle in the [FeO(2)](8) complex. The electronic structure of
      [FeO(2)](8) corresponds to Fe(III) (S = 5/2) antiferromagnetically coupled to
      O(2)(-) (S = 1/2), and, consistent with the extended bond length, the [FeO(2)](8)
      unit has only one Fe(III)-O(2)(-) bonding interaction, while the [FeNO](7) unit
      has both sigma and pi type Fe(III)-NO(-) bonds. This is in agreement with
      experiment as NO forms a more stable Fe(III)-NO(-) adduct relative to O(2)(-).
      Although NO is, in fact, harder to reduce, the resultant NO(-) species forms a
      more stable bond to Fe(III) relative to O(2)(-) due to the different bonding
      interactions.

PMID- 14719949
TI  - Selective formation of stable triplexes including a TA or a CG interrupting site
      with new bicyclic nucleoside analogues (WNA).
AB  - Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules and
      would become powerful tools for genomic research. As the stabilization of the TFO
      is partially provided by hydrogen bonds to purine bases, the most stable
      triplexes form with homopurine/homopyrimidine sequences, and a pyrimidine base in
      the purine strand of the duplex interrupts triplex formation. If a TFO can
      recognize sequences including such an interrupting site, the target regions in
      the genome would be expanded to a greater extent. However, this problem has not
      been generally solved despite extensive studies. We have previously reported a
      new base analogue (WNA) constructed of three parts, a benzene ring, a
      heterocyclic ring, and a bicyclic skeleton to hold these two parts. In this
      study, we have further investigated modification of WNA systematically and
      determined two useful WNA analogues, WNA-beta T and WNA-beta C, for selective
      stabilization of triplexes at a TA and a CG interrupting site, respectively. The
      triplexes with WNA analogues have exhibited an interesting property in that they
      are more stable than natural-type triplexes even at low Mg(2+) concentration.
      From comparison of the results with H-WNA-beta T lacking benzene and those with
      WNA-H without thymine, it has been suggested that benzene is a major contributor
      for triplex stability and thymine provides selectivity. Thus, it has been
      successfully demonstrated that WNA-beta T/TA and WNA-beta C/CG combinations may
      expand triplex recognition codes in addition to the natural A/AT and G/GC base
      triplet codes. The results of this study will provide useful information for the
      design of new WNA analogues to overcome inherent problems for further expansion
      of triplex recognition codes.

PMID- 14719950
TI  - Insights into the phosphoryl-transfer mechanism of cAMP-dependent protein kinase
      from quantum chemical calculations and molecular dynamics simulations.
AB  - To investigate the molecular details of the phosphoryl-transfer mechanism
      catalyzed by cAMP-dependent protein kinase, we performed quantum mechanical (QM)
      calculations on a cluster model of the active site and molecular dynamics (MD)
      simulations of a ternary complex of the protein with Mg(2)ATP and a 20-residue
      peptide substrate. Overall, our theoretical results confirm the participation of
      the conserved aspartic acid, Asp(166), as an acid/base catalyst in the reaction
      mechanism catalyzed by protein kinases. The MD simulation shows that the contact
      between the nucleophilic serine side chain and the carboxylate group of Asp(166)
      is short and dynamically stable, whereas the QM study indicates that an Asp(166)
      assisted pathway is structurally and energetically feasible and is in agreement
      with previous experimental results.

PMID- 14719951
TI  - Experimental and structural evidence that herpes 1 kinase and cellular DNA
      polymerase(s) discriminate on the basis of sugar pucker.
AB  - Two isomers of methanocarba (MC) thymidine (T), one an effective antiherpes agent
      with the pseudosugar moiety locked in the North (N) hemisphere of the
      pseudorotational cycle (1a, N-MCT) and the other an inactive isomer locked in the
      antipodean South (S) conformation (1b, S-MCT) were used to determine whether
      kinases and polymerases discriminate between their substrates on the basis of
      sugar conformation. A combined solid-state and solution conformational analysis
      of both compounds, coupled with the direct measurement of mono-, di-, and
      triphosphate levels in control cells, cells infected with the Herpes simplex
      virus, or cells transfected with the corresponding viral kinase gene (HSV-tk),
      suggests that kinases prefer substrates that adopt the S sugar conformation. On
      the other hand, the cellular DNA polymerase(s) of a murine tumor cell line
      transfected with HSV-tk incorporated almost exclusively the triphosphate of the
      locked N conformer (N-MCTTP), notwithstanding the presence of higher triphosphate
      levels of the S-conformer (S-MCTTP).

PMID- 14719952
TI  - Fluorogenic peptide sequences--transformation of short peptides into fluorophores
      under ambient photooxidative conditions.
AB  - Long-lived proteins are susceptible to nonenzymatic chemical reactions and the
      evolution of fluorescence; however, little is known about the sequence-dependence
      of fluorogenesis. We synthesized a library of over half a million octapeptides
      and exposed it to light and air in pH 7.4 buffer to identify fluorogenic peptides
      that evolve under mild oxidative conditions. The bead-based peptide library was
      composed of the general sequence H(2)N-Ala-(Xxx)(6)-Ala-resin, where Xxx was one
      of nine representative amino acids: Asp, Gly, His, Leu, Lys, Pro, Ser, Trp, and
      Tyr. Next, we selected five highly fluorescent beads from the library and
      subjected them to microsequencing, revealing the sequence of the unreacted
      peptide. All five of the fluorogenic sequences were ionic; lacked Tyr, His, and
      Leu; and most of the sequences contained only one Trp. We then synthesized the
      five soluble peptides corresponding to the fluorogenic peptide sequences and
      exposed them to photooxidative conditions. In general, the soluble peptides
      reacted slowly, generating nonfluorescent monooxygenated and dioxygenated
      products. However, one peptide (H(2)N-AlaLysProTrpGlyGlyAspAla-CONH(2)) evolved
      into a highly fluorescent photoproduct as well as a nonfluorescent monooxygenated
      photoproduct. The fluorescent photoproduct consisted of a 2-carboxy-quinolin-4-yl
      moiety fused to the N-terminus of GlyGlyAspAla. The formation of this
      photoproduct requires cleavage of the peptide backbone and a dramatic
      reorganization of tryptophan. This work demonstrates that sequencing unreacted
      peptide on beads can reveal sequences with unique nonenzymatic reactivity. The
      study also confirms that peptide fluorogenesis is dependent on sequence and not
      merely on the presence of tryptophan. The potential importance of fluorogenic
      peptide sequences is two-fold. First, fluorogenic sequences that arise through
      mutation could prove to be hot spots for human aging. Second, fluorogenic
      sequences, particularly those compatible with intracellular conditions, may serve
      as fluorescent tags for proteins or as fluorescent biomaterials.

PMID- 14719953
TI  - The SPR sensor detecting cytosine[bond]cytosine mismatches.
AB  - We have synthesized the first surface plasmon resonance (SPR) sensor that detects
      cytosine-cytosine (C[bond]C) mismatches in duplex DNA by immobilizing
      aminonaphthyridine dimer on the gold surface. The ligand consisting of two 2
      aminonaphthyridine chromophores and an alkyl linker connecting them strongly
      stabilized the C[bond]C mismatches regardless of the flanking sequences. The
      fully matched duplexes were not stabilized at all under the same conditions. The
      C[bond]T, C[bond]A, and T[bond]T mismatches were also stabilized with a reduced
      efficiency. SPR analyses of mismatch-containing 27-mer duplexes were performed
      with the sensor surface on which the aminonaphthyridine dimer was immobilized.
      The response for the C[bond]C mismatch in 5'-GCC-3'/3'-CCG-5' was about 83 times
      stronger than that obtained for the fully matched duplex. The sensor successfully
      detects the C[bond]C mismatch at the concentration of 10 nM. SPR responses are
      proportional to the concentration of the C[bond]C mismatch in a range up to 200
      nM. Aminonaphthyridine dimer could bind strongly to the C[bond]C mismatches
      having 10 possible flanking sequences with association constants in the order of
      10(6) M(-1). The facile protonation of 2-aminonaphthyridine chromophore at pH 7
      producing the hydrogen-bonding surface complementary to that of cytosine was most
      likely due to the remarkably high selectivity of 1 to the C[bond]C mismatch.

PMID- 14719954
TI  - One-step multifunctionalization of random copolymers via self-assembly.
AB  - A novel methodology for random copolymer functionalization based on a
      noncovalent, one-step, multifunctionalization strategy has been developed. Random
      copolymers possessing both palladated-pincer complexes and diaminopyridine
      moieties (hydrogen-bonding entities) have been synthesized using ring-opening
      metathesis polymerization. Noncovalent functionalization of the resultant
      copolymers is accomplished via (1) directed self-assembly, (2) multistep self
      assembly, and (3) one-step orthogonal self-assembly. This system shows complete
      specificity of each recognition motif for its complementary unit, with no
      observable changes in the association constants regardless of the degree of
      functionalization.

PMID- 14719955
TI  - Polyvalent scaffolds. Counting the number of seats available for eosin guest
      molecules in viologen-based host dendrimers.
AB  - We have prepared and investigated two dendrimers based on a 1,3,5-trisubstituted
      benzenoid-type core, containing 9 and 21 viologen units in their branches,
      respectively, and terminated with tetraarylmethane derivatives. We have shown
      that, in dichloromethane solution, such highly charged cationic species give rise
      to strong host-guest complexes with the dianionic form of the red dye eosin. Upon
      complexation, the absorption spectrum of eosin becomes broader and is slightly
      displaced toward lower energies, whereas the strong fluorescence of eosin is
      completely quenched. Titration experiments based on fluorescence measurements
      have shown that each viologen unit in the dendrimers becomes associated with an
      eosin molecule, so that the number of positions ("seats") available for the guest
      molecules in the hosting dendrimer is clearly established, e.g., 21 for the
      larger of the two dendrimers. The host-guest interaction can be destroyed by
      addition of chloride ions, a procedure which permits eosin to escape from the
      dendrimer's interior in a controlled way and to regain its intense fluorescence.
      When chloride anions are precipitated out by addition of silver cations, eosin
      molecules re-enter the dendrimer's interior and their fluorescence again
      disappears.

PMID- 14719956
TI  - Effects of spiroconjugation on the calculated singlet-triplet energy gap in 2,2
      dialkoxycyclopentane-1,3-diyls and on the experimental electronic absorption
      spectra of singlet 1,3-diphenyl derivatives. Assignment of the lowest-energy
      electronic transition of singlet cyclopentane-1,3-diyls.
AB  - The effect of a 2,2-ethylene-ketal functionality on the singlet-triplet energy
      gap (Delta E(ST)) and on the first electronic transition in singlet cyclopentane
      1,3-diyls (1) has been investigated. UDFT calculations predict a significant
      increase in the preference for a singlet ground state in the diradical with the
      cyclic ketal at C2 (1g; Delta E(ST) = -6.6 kcal/mol in C(2) symmetry and -7.6
      kcal/mol in C(2v) symmetry), compared to the 2,2-dihydroxy- and 2,2-dimethoxy
      disubstituted diradicals (1d, Delta E(ST) = -3.6 kcal/mol in C(2) symmetry, and
      1e, Delta E(ST) = -3.4 kcal/mol in C(2) symmetry). Spiroconjugation is shown to
      be responsible for the larger calculated value of absolute value Delta E(ST) in
      1g, relative to 1d and 1e. A strong correlation between the calculated values of
      Delta E(ST) and the computed electronic excitation energies of the singlet
      diradicals is found for diradicals 1d, 1e, and 1g and for 2,2
      difluorocyclopentane-1,3-diyl (1c). A similar correlation between Delta E(ST) and
      lambda(calcd) is predicted for the corresponding 1,3-diphenylcyclopentane-1,3
      diyls 3, and the predicted blue shift in the spectrum of 3g, relative to 3e, has
      been confirmed by experimental comparisons of the electronic absorption spectra
      of the annelated derivatives 2c, 2e, and 2g in a glass at 77 K. The wavelength of
      the first absorption band in the singlet diradicals decreases in the order 2e
      (lambda(onset) = 650 nm) > 2g (lambda(onset) = 590 nm) > 2c (lambda(onset) = 580
      nm). The combination of these computational and experimental results provides a
      sound basis for reassignment of the first electronic absorption band in singlet
      diradicals 2c, 2e, and 2g to the excitation of an electron from the HOMO to the
      LUMO of these 2,2-disubstituted derivatives of cyclopentane-1,3-diyl.

PMID- 14719957
TI  - Insight into G[bond]T mismatch recognition using molecular dynamics with time
      averaged restraints derived from NMR spectroscopy.
AB  - Molecular dynamics (MD) simulations were conducted for a G[bond]T mismatch
      containing DNA decamer, d(CCATGCGTGG)(2), and its Watson-Crick parent sequence,
      d(CCACGCGTGG)(2). Dynamics in unrestrained MD trajectories were in poor agreement
      with prior (13)C NMR studies. However, the accuracy of the trajectories was
      improved by the use of time-averaged interatomic distance restraints derived from
      (1)H NMR. Postprocess smoothing of the trajectories further improved accuracy.
      Comparison of restrained and smoothed trajectories of the two DNA molecules
      revealed distinct differences in dynamics. The major groove width of the
      mismatched oligomer was more variable over the course of the simulation compared
      to its parent sequence. Greater variability in helical parameters stretch and
      opening for the mismatches indicated less kinetically stable base pairing.
      Interbase helical parameters rise, roll, and tilt were also more variable in
      certain base steps involving mismatched bases. These dynamic differences between
      normal and G[bond]T mismatched DNA reflect differences in local flexibility that
      may play a role in mismatch recognition by the MutS. A potential alternate
      G[bond]T mismatch binding mode for MutS is also proposed.

PMID- 14719958
TI  - Mechanism of two-electron oxidation of deoxyguanosine 5'-monophosphate by a
      platinum(IV) complex.
AB  - Many transition metal complexes mediate DNA oxidation in the presence of
      oxidizing radiation, photosensitizers, or oxidants. The final DNA oxidation
      products vary depending on the nature of metal complexes and the structure of
      DNA. Here we propose a mechanism of oxidation of a nucleotide, deoxyguanosine 5'
      monophosphate (dGMP) by trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum
      (trans-Pt(d,l)(1,2-(NH(2))(2)C(6)H(10))Cl(4), [Pt(IV)Cl(4)(dach)]; dach =
      diaminocyclohexane) to produce 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'
      monophosphate (8-oxo-dGMP) stoichiometrically. The reaction was studied by high
      performance liquid chromatography (HPLC), (1)H and (31)P nuclear magnetic
      resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). The
      proposed mechanism involves Pt(IV) binding to N7 of dGMP followed by cyclization
      via nucleophilic attack of a phosphate oxygen at C8 of dGMP. The next step is an
      inner-sphere, two-electron transfer to produce a cyclic phosphodiester
      intermediate, 8-hydroxyguanosine cyclic 5',8-(hydrogen phosphate). This
      intermediate slowly converts to 8-oxo-dGMP by reacting with solvent H(2)O.

PMID- 14719959
TI  - The initial stages of solid acid-catalyzed reactions of adsorbed propane. A
      mechanistic study by in situ MAS NMR.
AB  - In situ solid-state NMR spectroscopy was employed to study the kinetics of
      hydrogen/deuterium exchange and scrambling as well as (13)C scrambling reactions
      of labeled propane over Al(2)O(3)-promoted sulfated zirconia (SZA) catalyst under
      mild conditions (30-102 degrees C). Three competitive pathways of isotope
      redistribution were observed during the course of the reaction: (1) a
      regioselective H/D exchange between acidic protons of the solid surface and the
      deuterons of the methyl group of propane-1,1,1,3,3,3-d(6), monitored by in situ
      (1)H MAS NMR; (2) an intramolecular H/D scrambling between methyl deuterons and
      protons of the methylene group, without exchange with the catalyst surface,
      monitored by in situ (2)H MAS NMR; (3) a intramolecular (13)C scrambling, by
      skeletal rearrangement process, favored at higher temperatures, monitored by in
      situ (13)C MAS NMR. The activation energy of (13)C scrambling was estimated to be
      very close to that of (2)H scrambling, suggesting that these two processes imply
      a common transition state, responsible for both vicinal hydride migration and
      protonated cyclopropane formation. All pathways are consistent with a classical
      carbenium ion-type mechanism.

PMID- 14719960
TI  - Total synthesis of hybocarpone and analogues thereof. A facile dimerization of
      naphthazarins to pentacyclic systems.
AB  - The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and
      related compounds is described. The successful route to hybocarpone features a
      novel radical-based dimerization/hydration cascade which generates the bridging
      hindered carbon-carbon bond of the molecule in a stereocontrolled manner, setting
      the relative configurations of the four contiguous stereocenters in a single
      step. The conjecture is made that this process may not be so dissimilar to the
      biosynthetic pathway leading to the formation of hybocarpone in nature. The
      developed sequence to these molecular frameworks also features the first example
      of a synthetically useful Diels-Alder trapping of a photochemically generated
      hydroxy-o-quinodimethane species with a 1,1-disubstituted olefin to form a
      quaternary center, and includes an efficient route to hydroxynaphthoquinone-type
      structures represented by the monomeric subunit of the natural product.

PMID- 14719961
TI  - Total synthesis of hamigerans and analogues thereof. Photochemical generation and
      Diels-Alder trapping of hydroxy-o-quinodimethanes.
AB  - A number of naturally occurring substances, including hamigerans, contain ring
      systems which are fused to an aromatic nucleus. A general and streamlined method
      for the construction of such benzannulated bi- and polycyclic carbon frameworks
      has been developed, and its scope and limitations were explored. On the basis of
      the photoenolization of substituted benzaldehydes and subsequent Diels-Alder
      (PEDA) trapping of the generated hydroxy-o-quinodimethanes, this method was
      optimized to set the stage for the total synthesis of several naturally occurring
      members of the hamigeran class. Specifically, the developed synthetic technology
      served as the centerpiece process for the successful asymmetric synthesis of
      hamigerans A (2), B (3), and E (7). In addition to the PEDA reactions, several
      other novel reaction processes are described, including a high-yielding
      decarbonylative ring contraction and an oxidative decarboxylation of a hydroxyl
      beta-keto ester to afford an alpha-diketone. A number of analogues of these
      biologically active natural products were also prepared by application of the
      developed technology.

PMID- 14719962
TI  - A benchtop method for the fabrication and patterning of nanoscale structures on
      polymers.
AB  - A benchtop method for the facile production of nanoscale metal structures on
      polymers is demonstrated. This approach allows for the design and patterning of a
      wide range of metallic structures on inexpensive polymer surfaces, affording the
      fabrication of nanoscaled platforms for use in the design of sensors, actuators,
      and disposable electronic and photonic devices. Numerous structures, from simple
      nanowires to multilayered metallic gratings, are demonstrated, with sizes ranging
      from microns to the nanoscale. The process involves molding a malleable metal
      film deposited on a rigid substrate such as mica, by the compression of a plastic
      polymer stamp with the desired pattern against the metal film. While under
      compression, an etchant is then used to modify the metal. Upon separation of the
      stamp from the support, micro- to nanoscaled metallic structures are found on the
      stamp and/or on the substrate. The sizes of the structures formed depend on the
      sizes of the features on the stamp but can be fine-tuned by about 4-fold through
      variations in both pressure and duration of etching. Also, depending on the
      processing, multiple dimension metallic structures can be obtained simultaneously
      in a single stamping procedure. The metallic structures formed on the stamp can
      also be subsequently transferred to another surface allowing for the construction
      of multilayered materials such as band gap gratings or the application of
      electrical contacts. Using this approach, fabrication of both simple and complex
      micro- to nanoscaled structures can be accomplished by most any researcher as
      even the grating structure of commercial compact disks may be used as stamps,
      eliminating the requirement of expensive lithographic processes to form simple
      structures.

PMID- 14719963
TI  - Controlled synthesis of 2-D and 3-D dendritic platinum nanostructures.
AB  - Seeding and autocatalytic reduction of platinum salts in aqueous surfactant
      solution using ascorbic acid as the reductant leads to remarkable dendritic metal
      nanostructures. In micellar surfactant solutions, spherical dendritic metal
      nanostructures are obtained, and the smallest of these nanodendrites resemble
      assemblies of joined nanoparticles and the nanodendrites are single crystals.
      With liposomes as the template, dendritic platinum sheets in the form of thin
      circular disks or solid foamlike nanomaterials can be made. Synthetic control
      over the morphology of these nanodendrites, nanosheets, and nanostructured foams
      is realized by using a tin-porphyrin photocatalyst to conveniently and
      effectively produce a large initial population of catalytic growth centers. The
      concentration of seed particles determines the ultimate average size and
      uniformity of these novel two- and three-dimensional platinum nanostructures.

PMID- 14719964
TI  - Facile ring opening of iron(III) and iron(II) complexes of meso-amino
      octaethylporphyrin by dioxygen.
AB  - Pyridine solutions of ClFe(III)(meso-NH(2)-OEP) undergo oxidative ring opening
      when exposed to dioxygen. The high-spin iron(III) complex, ClFe(III)(meso-NH(2)
      OEP), has been isolated and characterized by X-ray crystallography. In the solid
      state, it has a five-coordinate structure typical for high-spin (S = 5/2)
      iron(III) complex. In chloroform-d solution, ClFe(III)(meso-NH(2)-OEP) displays
      an (1)H NMR spectrum characteristic of a high-spin, five-coordinate complex and
      is unreactive toward dioxygen. However, in pyridine-d(5) solution a temperature
      dependent equilibrium exists between the high-spin (S = 5/2), six-coordinate
      complex, [(py)ClFe(III)(meso-NH(2)-OEP)], and the six-coordinate, low spin (S =
      1/2 with the less common (d(xz)d(yz))(4)(d(xy))(1) ground state)) complex,
      [(py)(2)Fe(III)(meso-NH(2)-OEP)](+). Such pyridine solutions are air-sensitive,
      and the remarkable degradation has been monitored by (1)H NMR spectroscopy. These
      studies reveal a stepwise conversion of ClFe(III)(meso-NH(2)-OEP) into an open
      chain tetrapyrrole complex in which the original amino group and the attached
      meso carbon atom have been converted into a nitrile group. Additional oxidation
      at an adjacent meso carbon occurs to produce a ligand that binds iron by three
      pyrrole nitrogen atoms and the oxygen atom introduced at a meso carbon. This open
      chain tetrapyrrole complex itself is sensitive to attack by dioxygen and is
      converted into a tripyrrole complex that is stable to further oxidation and has
      been isolated. The process of oxidation of the Fe(III) complex, ClFe(III)(meso
      NH(2)-OEP), is compared with that of the iron(II) complex, (py)(2)Fe(II)(meso
      NH(2)-OEP); both converge to form identical products.

PMID- 14719965
TI  - Prediction of solid solution formation in a family of diastereomeric salts. A
      molecular modeling study.
AB  - The possibility of solid solution behavior of diastereomeric salts, containing
      multiple resolving agents of the same family (Dutch Resolution), is predicted by
      molecular modeling. Super-cells containing different ratios of resolving agents
      in the diastereomeric salt are constructed and optimized, and their lattice
      energy is computed. The energy difference between these "simulated solid
      solutions" and the native structures is related in an understandable fashion to
      the probability of solid solution formation. This procedure is applied to a
      family of diastereomeric salts of ephedrine and cyclic phosphoric acids, for
      which the ternary diagrams have been determined experimentally at 25 degrees C in
      ethanol. Good agreement between experimental and computational results indicates
      that this relatively simple and fast method could predict the stable character of
      solid solution behavior in binary systems.

PMID- 14719966
TI  - Theoretical calculation of the NMR spin-spin coupling constants and the NMR
      shifts allow distinguishability between the specific direct and the water
      mediated binding of a divalent metal cation to guanine.
AB  - The calculated intermolecular and intramolecular indirect NMR spin-spin coupling
      constants and NMR shifts were used for the discrimination between the inner-shell
      and the outer-shell binding motif of hydrated divalent cations Mg(2+) or Zn(2+)
      with a guanine base. The intermolecular coupling constants (1)J(X,O6) and
      (1)J(X,N7) (X = Mg(2+), Zn(2+)) can be unambiguously assigned to the specific
      inner-shell binding motif of the hydrated cation either with oxygen O6 or with
      nitrogen N7 of guanine. The calculated coupling constants (1)J(Mg,O6) and
      (1)J(Zn,O6) were 6.2 and -17.5 Hz, respectively, for the inner-shell complex of
      cation directly interacting with oxygen O6 of guanine. For the inner-shell
      coordination of the cation at nitrogen N7, the calculated coupling constants
      (1)J(Mg,N7) and (1)J(Zn,N7) were 5.6 and -36.5 Hz, respectively. When the binding
      of the cation is water-mediated, the coupling constant is zero. To obtain
      reliable shifts in NMR parameters, hydrated guanine was utilized as the reference
      state. The calculated change of NMR spin-spin coupling constants due to the
      hydration and coordination of the cation with guanine is caused mainly by the
      variation of Fermi-contact coupling contribution while the variation of
      diamagnetic spin-orbit, paramagnetic spin-orbit, and spin-dipolar coupling
      contributions is small. The change of s-character of guanine sigma bonding, sigma
      antibonding, and lone pair orbitals upon the hydration and cation coordination
      (calculated using the Natural Bond Orbital analysis) correlates with the
      variation of the Fermi-contact term. The calculated NMR shifts delta(N7) of -15.3
      and -12.2 ppm upon the coordination of Mg(2+) and Zn(2+) ion are similar to the
      NMR shift of 19.6 ppm toward the high field measured by Tanaka for N7 of guanine
      upon the coordination of the Cd(2+) cation (Tanaka, Y.; Kojima, C.; Morita, E.
      H.; Kasai. Y.; Yamasaki, K.; Ono, A.; Kainosho, M.; Taira, K. J. Am. Chem. Soc.
      2002, 124, 4595-4601). The present data indicate that measurements of NMR
      intermolecular coupling constants may be used to discriminate between the
      specific inner- and outer-shell binding of divalent cations to nucleobases in DNA
      and RNA.

PMID- 14719967
TI  - Aligned inclusion of hemicyanine dyes into silica zeolite films for second
      harmonic generation.
AB  - Silicalite-1 films (thickness = 400 nm) supported on both sides of glass plates
      (SL/G) were prepared, and hemicyanine dyes (HC-n) with different alkyl chain
      lengths (n, n = 3, 6, 9, 12, 15, 18, 22, and 24) were included into the
      silicalite-1 films by dipping SL/Gs into each methanol solution of HC-n (1 mM)
      for 1 d. The included numbers of HC-n per channel (N(C)) generally decreased with
      increasing n; that is, they were 6.4, 23.1, 15.4, 8.2, 5.7, 3.5, 0.9, and 1.2
      molecules per channel, respectively. The d(33) value gradually increased with
      increasing n but decreased when n > 18; that is, they were 1.12, 0.50, 2.25,
      3.59, 4.99, 5.30, 1.71, and 2.57 pm V(-1), respectively. However, d(33)/N(C)
      progressively increased with increasing n. The d(31) values were approximately
      100 times smaller than the corresponding d(33) values, and the average
      d(33)/d(31) ratio was 109, which is higher than those of Langmuir-Blodgett (LB)
      films and poled polymers of nonlinear optical (NLO) dyes, by approximately 2-5
      and approximately 30-50 times, respectively. The estimated average tilted angle
      of the dyes with respect to the channel direction was 7.7 degrees, and the
      calculated average order parameter was 0.97, which is approximately 480 times
      higher than the values observed from poled polymers. The degree of uniform
      alignment (DUA) generally increased with increasing n. The progressive increase
      of both DUA and d(33)/N(C) with n is attributed to the increase in the tendency
      of HC-n to enter hydrophobic silicalite-1 channels with the hydrophobic alkyl
      chain first. A more than 134-fold increase in DUA was observed upon increasing n
      from 6 to 24. The DUA of HC-24 in the silicalite-1 film reached close to 1.
      Although the observed d(33) values were lower than those of the LB films of NLO
      dyes due to very small dye densities of the silicalite films, this methodology
      bears a great potential to be developed into the methods for preparing
      practically viable NLO films.

PMID- 14719968
TI  - Photophysical properties of ruthenium(II) polyazaaromatic compounds: a
      theoretical insight.
AB  - Quantum-chemical methods are applied to study the nature of the excited states
      relevant in the photophysical processes (absorption and emission) of a series of
      polyazaaromatic-ligand-based ruthenium(II) complexes. The electronic and optical
      properties of the free polyazaaromatic ligands and their corresponding
      ruthenium(II) complexes are determined on the basis of correlated Hartree-Fock
      semiempirical approaches. While the emission of complexes containing small-size
      ligands, such as 1,10-phenanthroline or 2,2'-bipyridine, arises from a manifold
      of metal-to-ligand charge-transfer triplet states ((3)MLCTs), an additional
      ligand-centered triplet state ((3)L) is identified in the triplet manifold of
      complexes containing a pi-extended ligand such as dipyrido[3,2-a:2',3'
      c]phenazine, tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine, and 1,10
      phenanthrolino[5,6-b]-1,4,5,8,9,12-hexaazatriphenylene. Recent experimental data
      are interpreted in light of these theoretical results; namely, the origin for the
      abnormal solvent- and temperature-dependent emission measured in pi-extended Ru
      complexes is revisited.

PMID- 14719970
TI  - Fluorinated carbonyl and olefinic compounds: basic character and asymmetric
      catalytic reactions.

PMID- 14719972
TI  - HDL: the metabolism, function, and therapeutic importance.

PMID- 14719973
TI  - Upconversion and anti-Stokes processes with f and d ions in solids.

PMID- 14719974
TI  - Quantitative measures of solvent polarity.

PMID- 14719975
TI  - Protection (and deprotection) of functional groups in organic synthesis by
      heterogeneous catalysis.

PMID- 14719976
TI  - Synthesis of thiiranes by direct sulfur transfer: the challenge of developing
      effective sulfur donors and metal catalysts.

PMID- 14719977
TI  - Synthesis and Uses of exo-Glycals.

PMID- 14719978
TI  - Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related
      properties, and applications toward biology, catalysis, and nanotechnology.

PMID- 14719979
TI  - Global positioning system and sport-specific testing.
AB  - Most physiological testing of athletes is performed in well-controlled situations
      in the laboratory. Multiple factors that are hard to control for have limited the
      use of sport-specific field testing. Recently, the technique of the differential
      global positioning system (dGPS) has been put forward as a way to monitor the
      position and speed of an athlete during outdoor activities with acceptable
      precision, thus controlling the two most important factors of performance in
      endurance athletics, i.e. inclination and speed. A detailed analysis of
      performance has been shown to be possible in combination with metabolic gas
      measurements. The combination of accelerometry and dGPS has also been shown to
      improve physiological field testing. The technique of dGPS could probably also be
      combined with other bio-measurements (e.g. electromyography and cycling cadence
      and power) and may enable other studies of exercise physiology in the field,
      otherwise restricted to the laboratory environment. This technique may also be of
      use in general exercise physiology where monitoring of patients with, for
      example, cardiovascular and pulmonary diseases, could be of interest for the
      future.

PMID- 14719980
TI  - A framework for understanding the training process leading to elite performance.
AB  - The development of performance in competition is achieved through a training
      process that is designed to induce automation of motor skills and enhance
      structural and metabolic functions. Training also promotes self-confidence and a
      tolerance for higher training levels and competition. In general, there are two
      broad categories of athletes that perform at the highest level: (i) the
      genetically talented (the thoroughbred); and (ii) those with a highly developed
      work ethic (the workhorse) with a system of training guiding their effort. The
      dynamics of training involve the manipulation of the training load through the
      variables: intensity, duration and frequency. In addition, sport activities are a
      combination of strength, speed and endurance executed in a coordinated and
      efficient manner with the development of sport-specific characteristics. Short-
      and long-term planning (periodisation) requires alternating periods of training
      load with recovery for avoiding excessive fatigue that may lead to overtraining.
      Overtraining is long-lasting performance incompetence due to an imbalance of
      training load, competition, non-training stressors and recovery. Furthermore,
      annual plans are normally constructed in macro-, meso- and microcycles around the
      competitive phases with the objective of improving performance for a peak at a
      predetermined time. Finally, at competition time, optimal performance requires a
      healthy body, and integration of not only the physiological elements but also the
      psychological, technical and tactical components.

PMID- 14719981
TI  - Endurance training and aerobic fitness in young people.
AB  - Training-induced adaptations in aerobic fitness have been extensively studied in
      adults, and some exercise scientists have recommended similar training programmes
      for young people. However, the subject of the response to aerobic training of
      children and adolescents is controversial. The effects of exercise training on
      prepubertal children are particularly debatable. The latter may be partly
      explained by different training designs, which make comparisons between studies
      very problematic. We have analysed the procedures applied to protocol design and
      training methods to highlight the real impact of aerobic training on the peak
      oxygen uptake (V-dotO2) of healthy children and adolescents. In accordance with
      previously published reviews on trainability in youngsters, research papers were
      rejected from the final analysis according to criteria such as the lack of a
      control group, an unclear training protocol, inappropriate statistical
      procedures, small sample size, studies with trained or special populations, or
      with no peak V-dotO2 data. Factors such as maturity, group constitution,
      consistency between training and testing procedures, drop out rates, or
      attendance were considered, and possible associations with changes in peak V
      dotO2 with training are discussed. From 51 studies reviewed, 22 were finally
      retained. In most of the studies, there was a considerable lack of research
      regarding circumpubertal individuals in general, and particularly in girls. The
      results suggest that methodologically listed parameters will exert a potential
      influence on the magnitude of peak V-dotO2 improvement. Even if little difference
      is reported for each parameter, it is suggested that the sum of errors will
      result in a significant bias in the assessment of training effects. The
      characteristics of each training protocol were also analysed to establish their
      respective potential influence on peak V-dotO2 changes. In general, aerobic
      training leads to a mean improvement of 5-6% in the peak V-dotO2 of children or
      adolescents. When only studies that reported significant training effect were
      taken into account, the mean improvement in peak V-dotO2 rose to 8-10%. Results
      suggested that intensities higher than 80% of maximal heart rate are necessary to
      expect a significant improvement in peak V-dotO2. There is clearly a need for
      longitudinal or cross-sectional studies that investigate the relationship between
      maturity and training with carefully monitored programmes. Further research is
      also needed to compare interval training and continuous training.

PMID- 14719982
TI  - Prevention and treatment of ankle sprain in athletes.
AB  - The frequent nature of ankle sprains and persistent disability that often ensues
      has lead to considerable medical costs. As prevention of disease and injury
      becomes an increasingly important part of the practice of medicine today, we
      strive to understand and identify interventions that optimally reduce the
      frequency of ankle sprain and re-injury. In doing so, considerable morbidity and
      unnecessary medical expenditures may potentially be averted. The prophylactic use
      of ankle braces is fairly common. Recent critical evaluation of their
      effectiveness supports their use for at least 6 months following injury in
      athletes who have sustained a moderate or severe sprain; however, their role in
      primary prevention of ankle sprain is less evident. Functional ankle
      rehabilitation is the mainstay of acute ankle sprain treatment and in recent
      reviews has been deemed preferable to immobilisation or early surgery for initial
      treatment of acutely injured ankles. Furthermore, certain components of ankle
      rehabilitation, such as proprioceptive exercises, have been found to protect the
      joint from re-injury. Multifaceted ankle sprain prevention programmes that
      incorporate a variety of strategies for injury reduction are also effective in
      sprain prevention, although the relative importance of each component of such
      programmes warrants further investigation. Surgery for ankle sprain is
      principally reserved for patients who fail a comprehensive non-operative
      treatment programme and can be highly successful in treating chronic functional
      instability. This paper examines the current literature regarding common ankle
      sprain prevention strategies and provides a review of appropriate treatment
      schemes.

PMID- 14719983
TI  - The emerging role of leukotriene modifiers in allergic rhinitis.
AB  - Leukotriene modifiers have been shown to be efficacious in the treatment of
      asthma. Because of this success, and the fact that leukotrienes can be recovered
      not only from bronchoalveolar lavage fluid but also nasal lavage fluid, some
      researchers have suggested that these medications may also be useful for treating
      allergic rhinitis. Because the upper and lower airways are linked physically,
      there has been an assumption that therapy for upper and lower airway disease
      should be similar. This critical appraisal examines available data both
      supporting and refuting the emerging role of leukotriene modifiers in the
      treatment of allergic rhinitis. Although many studies have shown an improvement
      in nasal symptoms when comparing a leukotriene modifier with placebo, few studies
      have conclusively shown that a leukotriene modifier is any more effective in
      treating allergic rhinitis than an antihistamine. Results from several reported
      studies suggest that the addition of a leukotriene antagonist to an antihistamine
      is no more efficacious than antihistamine alone. However, many of these studies
      were small and/or primarily designed to examine the asthmatic response, with
      nasal symptoms being a lesser endpoint. To better understand how, where, and when
      leukotriene modifiers should be used in the armamentarium of therapies for
      allergic rhinitis, larger clinical investigations designed specifically to study
      allergic rhinitis need to be undertaken. We conclude that currently, the data do
      not support widespread use of a leukotriene modifier with or without an
      antihistamine in place of an intranasal corticosteroid with or without an
      antihistamine in the treatment of allergic rhinitis.

PMID- 14719984
TI  - Is there a role for systemic corticosteroids in the management of stable chronic
      obstructive pulmonary disease?
AB  - COPD, encompassing both chronic bronchitis and emphysema, usually results from
      exposure to tobacco smoke. Smoking causes infiltration of the airways with
      leukocytes, an imbalance between proteases and their naturally occurring
      inhibitors and local cytokine secretion in the lung, which leads to airway
      inflammation and alveolar destruction. Corticosteroids have a range of anti
      inflammatory actions, particularly inhibition of cytokine secretion, which
      suggests that they may be effective in COPD. However, data from the highest
      quality studies available do not show any evidence of significant improvement in
      symptoms of patients with COPD treated with systemic corticosteroids.A meta
      analysis found that about 10% of patients with stable COPD showed an improvement
      in lung function following treatment with short-term systemic corticosteroids
      compared with placebo. Exercise capacity in patients with COPD was evaluated in
      four studies, only one of which found a significant improvement with oral
      corticosteroids compared with placebo. Long-term systemic corticosteroid
      treatment in patients with stable COPD has not been found to alter the rate of
      decline in FEV(1). Although systemic corticosteroids are associated with a range
      of adverse effects, the data do not allow precise quantification of their
      contribution to morbidity. However, studies show an increased risk of
      osteoporosis in COPD. Recent studies have also found an association between oral
      corticosteroid administration and mortality in patients with stable COPD, but it
      is not clear if this is a cause and effect relationship. Current data do not
      support long-term administration of systemic corticosteroids to all patients with
      stable COPD. Results of studies suggest that short-term oral corticosteroid
      administration may identify a sub-population of patients with COPD who may
      benefit through a reduction in the decline in FEV(1) and better control of
      symptoms by long-term administration of inhaled corticosteroids; these findings
      need to be tested by further research.

PMID- 14719985
TI  - Pseudomonal infections in patients with COPD: epidemiology and management.
AB  - COPD is a common disease with increasing prevalence. The chronic course of the
      disease is characterized by acute exacerbations that cause significant worsening
      of symptoms. Bacterial infections play a dominant role in approximately half of
      the episodes of acute exacerbations of COPD. The importance of pseudomonal
      infection in patients with acute exacerbations of COPD stems from its relatively
      high prevalence in specific subgroups of these patients, and particularly its
      unique therapeutic ramifications. The colonization rate of Pseudomonas aeruginosa
      in patients with COPD in a stable condition is low.A review of a large number of
      clinical series of unselected outpatients with acute exacerbations of COPD
      revealed that P. aeruginosa was isolated from the patients' sputum at an average
      rate of 4%. This rate increased significantly in COPD patients with advanced
      airflow obstruction, in whom the rate of sputum isolates of P. aeruginosa reached
      8-13% of all episodes of acute exacerbations of COPD. However, the great majority
      of bacteria isolated in these patients were not P. aeruginosa, but the three
      classic bacteria Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella
      catarrhalis. The subgroup of patients, with acute exacerbations of COPD, with the
      highest rate of P. aeruginosa infection, which approaches 18% of the episodes, is
      mechanically ventilated patients. However, even in this subgroup the great
      majority of bacteria isolated are the above-mentioned three classic pathogens. In
      light of these epidemiologic data and other important considerations, and in
      order to achieve optimal antibacterial coverage for the common infectious
      etiologies, empiric antibacterial therapy should be instituted as follows.
      Patients with acute exacerbations of COPD with advanced airflow obstruction
      (FEV(1) <50% of predicted under stable conditions) should receive once daily oral
      therapy with one of the newer fluoroquinolones, i.e. levofloxacin, moxifloxacin,
      gatifloxacin, or gemifloxacin for 5-10 days. Patients with severe acute
      exacerbations of COPD who are receiving mechanical ventilation should receive
      amikacin in addition to one of the intravenous preparations of the newer
      fluoroquinolones or monotherapy with cefepime, a carbapenem or
      piperacillin/tazobactam. In both subgroups it is recommended that sputum cultures
      be performed before initiation of therapy so that the results can guide further
      therapy.

PMID- 14719986
TI  - The etiology and management of pregnancy rhinitis.
AB  - Pregnancy rhinitis is defined as nasal congestion in the last 6 or more weeks of
      pregnancy, without other signs of respiratory tract infection and with no known
      allergic cause, with complete resolution of symptoms within 2 weeks after
      delivery. Pregnancy rhinitis occurs in approximately one-fifth of pregnancies,
      can appear at almost any gestational week, and affects the woman and possibly
      also the fetus. The pathogenesis of pregnancy rhinitis is not clear, but
      placental growth hormone is suggested to be involved. Smoking and sensitization
      to house dust mites are probable risk factors. It is often difficult to make a
      differential diagnosis from sinusitis: nasendoscopy of a decongested nose is the
      diagnostic method of choice. In some cases ultrasound or x-ray may be necessary.
      Sinusitis should be treated aggressively with increased doses of beta-lactam
      antibiotics and antral irrigation. Nasal decongestants give good temporary relief
      from pregnancy rhinitis, but they tend to be overused, leading to the development
      of rhinitis medicamentosa. Corticosteroids have not been shown to be effective in
      pregnancy rhinitis, and their systemic administration should be avoided during
      pregnancy. Nasal corticosteroids may be administered to pregnant women when
      indicated for other sorts of rhinitis. Nasal alar dilators and saline washings
      are safe means to relieve nasal congestion, but the ultimate treatment for
      pregnancy rhinitis remains to be found.

PMID- 14719987
TI  - Combined modality treatment of non-small-cell lung cancer.
AB  - Among all nonmetastatic non-small-cell lung cancer (NSCLC) patients, the best
      survival rates are observed in patients who undergo surgery. Nevertheless, 5-year
      survival rates vary between 20% and 60% depending on the stage of the disease.
      Several combined modality treatments have been investigated to improve outcome in
      localized NSCLC. These include local treatment, systemic before local treatment,
      concomitant systemic and local treatments, and systemic after local treatment.
      Preoperative irradiation was shown to be of no benefit on local recurrence rates
      or overall survival. Even doses of radiation >/=40 grays (Gy) were associated
      with lower survival rates. Postoperative irradiation did not influence survival
      in stage III disease and seemed to be deleterious in stages I and II disease.
      Modern radiotherapy techniques might be of interest in this setting but have been
      insufficiently tested. The early phase III studies of preoperative chemotherapy
      versus primary surgery in stage III NSCLC showed a tremendous difference in favor
      of chemotherapy. A larger study did not confirm these results but suggested that
      preoperative chemotherapy might have a greater effect in stages I and II of the
      disease. In locally advanced disease, chemotherapy followed by radiotherapy was
      shown to increase survival when compared with radiotherapy alone. Studies
      comparing concurrent chemoradiation with radiotherapy only were in favor of the
      concomitant schedule, which improved local control. Promising results have been
      reported with chemoradiation followed by surgery in stage IIIa and even stage
      IIIb disease. Randomized studies of postoperative chemotherapy demonstrated a 5%
      improvement in 5-year survival over adjuvant-free treatment. Postoperative
      chemoradiation showed no advantage over postoperative radiotherapy. Several
      trials that are ongoing or whose accrual was recently completed should further
      define the role of perioperative chemotherapy in resectable NSCLC and of
      trimodality treatments in advanced disease. Targeted agents are being developed
      in the postoperative setting. New schedules of chemoradiation with higher
      therapeutic indexes are also being investigated in nonresectable stage III NSCLC.

PMID- 14719988
TI  - Antibiotic prescribing patterns of French GPs for upper respiratory tract
      infections: impact of fusafungine on rates of prescription of systemic
      antibiotics.
AB  - INTRODUCTION: Despite attempts to limit their use, systemic antibiotics are
      extensively prescribed for respiratory infections in France. This survey analyzed
      data from the Thales database, which contains information from 1010
      representative French general practitioners (GPs). The objective was to assess
      French GP prescribing patterns in upper respiratory tract infections (URTIs)
      including the rate of prescription of systemic antibiotics and anti-inflammatory
      drugs in the presence or absence of prescribing fusafungine (Locabiotal) an
      antibiotic with anti-inflammatory activity indicated for local use in URTIs. Drug
      costs to the French National Sickness Fund were also assessed. METHODS: This was
      a retrospective, longitudinal, case-control analysis. Prescribing patterns and
      costs were compared between patients who did and patients who did not receive
      fusafungine for a URTI (rhinopharyngitis, tonsillitis, or an influenza-like
      condition). The fusafungine group consisted of all patients in the database who
      were prescribed fusafungine at least once between 1 December 1999 and 30 November
      2000. The control group was made up of randomly selected patients, matched for
      age and sex with the study group, who received at least one drug prescription
      (but not fusafungine) for a URTI during the same period. Patients were selected
      at the time of their first prescription, and their records for 1 year were
      analyzed. RESULTS: Each group contained 22 164 patients. For URTIs overall,
      systemic antibiotics were widely prescribed (at a rate of 54.6% and 67.8% in the
      fusafungine and control groups, respectively; p < 0.01). The rate of prescription
      of systemic antibiotics, NSAIDs and corticosteroids per prescription and per
      episode was significantly lower in the fusafungine group than in the control
      group. The mean cost per prescription for the French National Sickness Fund was
      significantly lower for the three URTIs overall when fusafungine was prescribed
      (9.21 euros [euro] vs euro9.67; p < 0.01). The mean cost to the National Sickness
      Fund per prescription of systemic antibiotics, NSAIDs, and corticosteroids was
      also significantly lower in the fusafungine group compared with the control
      group. The cost of nasal preparations was higher in the fusafungine group because
      Locabiotal is classified as a nasal preparation. The cost per prescription to the
      National Sickness Fund was increased by the presence of systemic antibiotics,
      NSAIDs, or corticosteroids among the prescribed drugs and decreased with the
      prescription of fusafungine. CONCLUSION: When fusafungine was prescribed for
      URTIs, fewer systemic antibiotics were prescribed, an important result in the
      current context of concern about emerging antibiotic resistance. The use of
      fusafungine was associated with a lower mean cost per prescription to the French
      National Sickness Fund.

PMID- 14719989
TI  - Preventing exacerbations of chronic bronchitis and COPD: therapeutic potential of
      mucolytic agents.
AB  - It is important to find interventions that will reduce the frequency and severity
      of exacerbations of COPD, because of their effect on morbidity and healthcare
      expenditure. A Cochrane systematic review included 23 studies that had evaluated
      the effects of treatment with mucolytic agents in patients with chronic
      bronchitis or COPD. Mucolytic treatment was associated with a significant
      reduction of 0.79 exacerbations per patient per year compared with placebo, a 29%
      decrease. Patients who received treatment with mucolytic agents were twice as
      likely to remain exacerbation-free in the study period than if they had received
      placebo, with six patients needing regular treatment with mucolytic agents for 3
      6 months to achieve one less exacerbation over that time. Treatment with
      mucolytic agents resulted in nearly 7 days less illness per patient per year. How
      mucolytic agents work is unknown, although they may reduce exacerbations by
      altering mucus production, antioxidation, or antibacterial or immunostimulatory
      effects. They do not appear to affect the decline in lung function that occurs in
      COPD. The treatment appears to be without any adverse effects, apart from the
      need to take oral medication daily. Cost-effectiveness analysis suggests that the
      point at which the costs of treatment and non-treatment were equal was 1.2 less
      exacerbations per year. This is higher than the effect observed in the Cochrane
      review, suggesting that treating everyone with COPD with mucolytic agents would
      not be cost effective. Those with more frequent and severe exacerbations appear
      to have the most to gain.

PMID- 14719990
TI  - New and emerging antifungal agents: impact on respiratory infections.
AB  - Fungal pathogens are increasingly important causes of respiratory disease, yet
      the number of antifungal agents available for clinical use is limited. Use of
      amphotericin B deoxycholate is hampered by severe toxicity. Triazole agents
      currently available have significant drug interactions; fluconazole has a limited
      spectrum of activity and itraconazole was, until recently, available only in oral
      formulations with limited bioavailability. The development of resistance to all
      three agents is increasingly being recognized and some filamentous fungi are
      resistant to the action of all of these agents. In the past few years, new
      antifungal agents and new formulations of existing agents have become
      available.The use of liposomal amphotericin B preparations is associated with
      reduced, but still substantial, rates of nephrotoxicity and infusion-related
      reactions. An intravenous formulation of itraconazole has been introduced, and
      several new triazole agents have been developed, with the view of identifying
      agents that have enhanced potency, broader spectra of action and improved
      pharmacodynamic properties. One of these, voriconazole, has completed large-scale
      clinical trials. In addition, caspofungin, the first of a new class of agents,
      the echinocandins, which inhibit cell wall glucan synthesis, was approved for use
      in the US in 2001 as salvage therapy for invasive aspergillosis. It is hoped that
      the availability of these agents will have a significant impact on the morbidity
      and mortality of fungal respiratory infections. However, at the present time, our
      ability to assess their impact is limited by the problematic nature of conducting
      trials for antifungal therapy.

PMID- 14719991
TI  - Management of community-acquired pneumonia: a focus on conversion from hospital
      to the ambulatory setting.
AB  - Patients with community-acquired pneumonia (CAP) are treated in hospital or in
      the ambulatory care setting depending on the severity of illness. Despite
      numerous guidelines proposed, there is no agreement on specific criteria for
      hospitalization other than the clinicians' experience. The purpose of this review
      is to discuss the importance of the appropriate choice and timely administration
      of antibacterial agents, either in the hospital or in the outpatient setting.
      Since a high proportion of CAP patients will not have an etiologic agent
      identified at the time of initiation of treatment, the choice of antibacterial
      therapy is usually empiric. Antibacterial agents with activity against
      pneumococci and atypical pathogens causing pneumonia are the preferred choices.
      Macrolides, doxycycline, or respiratory fluoroquinolones have been recommended by
      various guidelines committees in North America for the treatment of pneumonia in
      patients with or without underlying comorbidities. Because of the increasing
      resistance to beta-lactams as well other antibacterial agents such as macrolides,
      doxycycline, and sulfamethoxazole/trimethoprim (cotrimoxazole), it is important
      that clinicians are aware of local statistics on resistance to Streptococcus
      pneumoniae, as infection with this bacterium is associated with high rates of
      morbidity and mortality. More recently, fluoroquinolone resistance has been
      reported, but the percentage of pneumococcal strains resistant to this agent is
      relatively low compared with the other antibacterial agents. Switch (intravenous
      to oral) therapy is recommended for hospitalized patients with CAP to facilitate
      early discharge, which has been shown to improve patient satisfaction and reduce
      hospital costs. Early conversion to oral therapy has not been shown to be
      associated with increased complications or higher mortality. Following prompt
      intravenous therapy and stabilization, patients with CAP should be treated with
      oral therapy in the ambulatory setting.

PMID- 14719992
TI  - Prevention and treatment of gastrointestinal complications in patients on
      mechanical ventilation.
AB  - There exists a complex, dynamic interaction between mechanical ventilation and
      the splanchnic vasculature that contributes to a myriad of gastrointestinal tract
      complications that arise during critical illness. Positive pressure-induced
      splanchnic hypoperfusion appears to play a pivotal role in the pathogenesis of
      these complications, the most prevalent of which are stress-related mucosal
      damage, gastrointestinal hypomotility and diarrhea. Furthermore, characteristics
      of the splanchnic vasculature make the gastrointestinal tract vulnerable to
      adverse effects related to positive pressure ventilation. While most of these
      complications seen in mechanically ventilated patients are reflections of altered
      gastrointestinal physiology, some may be attributed to medical interventions
      instituted to treat critical illness. Since maintenance of normal hemodynamics
      cannot always be achieved, pharmacologic prophylactic therapy has become a
      mainstay in the prevention of gastrointestinal complications in the intensive
      care unit. Improved understanding of the systemic effects of mechanical
      ventilation and greater application of lung-protective ventilatory strategies may
      potentially minimize positive pressure-induced reductions in splanchnic
      perfusion, systemic cytokine release and, consequently, reduce the incidence of
      gastrointestinal complications associated with mechanical ventilation. Herein, we
      discuss the pathophysiology of gastrointestinal complications associated with
      mechanical ventilation, summarize the most prevalent complications and focus on
      preventive strategies and available treatment options for these complications.
      The most common causes of gastrointestinal hemorrhage in mechanically ventilated
      patients are bleeding from stress-related mucosal damage and erosive esophagitis.
      In general, histamine H(2) receptor antagonists and proton pump inhibitors
      prevent stress-related mucosal disease by raising the gastric fluid pH. Proton
      pump inhibitors tend to provide more consistent pH control than histamine H(2)
      receptor antagonists. There is no consensus on the drug of choice for stress
      ulcer prophylaxis with several meta-analyses providing conflicting results on the
      superiority of any medication. Prevention of erosive esophagitis include careful
      use of nasogastric tubes and institution of strategies that improve gastric
      emptying. Many mechanically ventilated patients have gastrointestinal
      hypomotility and diarrhea. Treatment options for gastrointestinal motility are
      limited, thus, preventive measures such as correction of electrolyte
      abnormalities and avoidance of medications that impair gastrointestinal motility
      are crucial. Treatment of diarrhea depends on the underlying cause. When
      associated with Clostridium difficile infection antibacterial therapy should be
      discontinued, if possible, and treatment with oral metronidazole should be
      initiated.More studies are warranted to better understand the systemic effects of
      mechanical ventilation on the gastrointestinal tract and to investigate the
      impact of lung protective ventilatory strategies on gastrointestinal
      complications.

PMID- 14719993
TI  - Pharmacological approaches to correcting the ion transport defect in cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a lethal genetic disease caused by a mutation in a
      membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR),
      which mainly (but not exclusively) functions as a chloride channel. The main
      clinical symptoms are chronic obstructive lung disease, which is responsible for
      most of the morbidity and mortality associated with CF, and pancreatic
      insufficiency. About 1000 mutations of the gene coding for CFTR are currently
      known; the most common of these, present in the great majority of the patients
      (Delta508) results in the deletion of a phenylalanine at position 508. In this
      mutation, the aberrant CFTR is not transported to the membrane but degraded in
      the ubiquitin-proteasome pathway. The aim of this review is to give an overview
      of the pharmacologic strategies currently used in attempts to overcome the ion
      transport defect in CF. One strategy to develop pharmacologic treatment for CF is
      to inhibit the breakdown of DeltaF508-CFTR by interfering with the chaperones
      involved in the folding of CFTR. At least in in vitro systems, this can be
      accomplished by sodium phenylbutyrate, or S-nitrosoglutathione (GSNO), and also
      by genistein or benzo[c]quinolizinium compounds. It is also possible to stimulate
      CFTR or its mutated forms, when present in the plasma membrane, using xanthines,
      genistein, and various other compounds, such as benzamidizoles and benzoxazoles,
      benzo[c]quinolizinium compounds or phenantrolines. Experimental results are not
      always unambiguous, and adverse effects have been incompletely tested. Some
      clinical tests have been done on sodium phenyl butyrate, GSNO and genistein,
      mostly in respect to other diseases, and the results demonstrate that these drugs
      are reasonably well tolerated. Their efficiency in the treatment of CF has not
      yet been demonstrated, however. An alternative strategy is to compensate for the
      defective chloride transport by CFTR by stimulation of other chloride channels.
      This can be done via purinergic receptors. A phase I study using a stable uridine
      triphosphate analog has recently been completed. A second alternative strategy is
      to attempt to maintain hydration of the airway mucus by inhibiting Na(+) uptake
      by the epithelial Na(+) channel using amiloride or stable analogs of amiloride.
      Clinical tests so far have been inconclusive. A number of other suggestions are
      currently being explored. The minority of patients with CF who have a stop
      mutation may benefit from treatment with gentamicin. The difficulties in finding
      a pharmacologic treatment for CF may be due to the fact that CFTR has additional
      functions besides chloride transport, and interfering with CFTR biosynthesis or
      activation implies interference with central cellular processes, which may have
      undesirable adverse effects.

PMID- 14719994
TI  - Relationship between changes in quality of life and measures of lung function and
      bronchial hyper-responsiveness during high-dose inhaled corticosteroid treatment
      in uncontrolled asthma.
AB  - OBJECTIVE: To examine the relationship between changes in quality of life and
      measures of lung function and bronchial hyper-responsiveness (BHR) during
      treatment with high-dose inhaled corticosteroids in patients with uncontrolled
      asthma. METHODS: Thirty patients with uncontrolled asthma currently receiving
      inhaled corticosteroids (median dose 550 microg/day) were treated with
      beclomethasone dipropionate (BDP) dry powder 2000 microg/day for 4 weeks.
      Patients completed the Asthma Quality of Life Questionnaire (AQLQ), underwent
      bronchial challenge with methacholine and spirometry, and made entries in asthma
      diary cards at baseline and after treatment with beclomethasone dipropionate.
      RESULTS: The mean change in overall AQLQ score improved significantly (p < 0.05)
      during the 4-week period by 0.57 (95% CI 0.29-0.84, p < 0.05), representing a
      minimal important difference, with similar improvements in individual domains.
      Change in overall AQLQ score correlated significantly with FEV(1) (p < 0.001),
      forced mid-expiratory flow between 25-75% of vital capacity (FEF(25-75)) [p <
      0.05] and morning PEF (p < 0.05), but not with methacholine PD(20) i.e. the
      provocative dose of methacholine causing a 20% fall in FEV(1). CONCLUSIONS:
      Quality-of-life scores related to changes in lung function but not BHR during
      short-term high-dose inhaled corticosteroid therapy for uncontrolled asthma.

PMID- 14719995
TI  - Adverse effects of beta-agonists: are they clinically relevant?
AB  - Inhaled beta(2)-adrenoceptor agonists (beta(2)-agonists) are the most commonly
      used asthma medications in many Western countries. Minor adverse effects such as
      palpitations, tremor, headache and metabolic effects are predictable and dose
      related. Time series studies suggested an association between the relatively
      nonselective beta-agonist fenoterol and asthma deaths. Three case-control studies
      confirmed that among patients prescribed fenoterol, the risk of death was
      significantly elevated even after controlling for the severity of asthma. The
      Saskatchewan study not only found an increased risk of death among patients
      dispensed fenoterol, but also suggested this might be a class effect of beta(2)
      agonists. However, in subsequent studies, the long-acting beta(2)-agonist
      salmeterol was not associated with increased asthma mortality. In a case-control
      study blood albuterol (salbutamol) concentrations were found to be 2.5 times
      higher among patients who died of asthma compared with controls. It is speculated
      that such toxic concentrations could cause tachyarrhythmias under conditions of
      hypoxia and hypokalemia. The risk of asthma exacerbations and near-fatal attacks
      may also be increased among patients dispensed fenoterol, but this association
      may be largely due to confounding by severity. Although salmeterol does not
      appear to increase the risk of near-fatal attacks, there is a consistent
      association with the use of nebulized beta(2)-agonists. Nebulized and oral
      beta(2)-agonists are also associated with an increased risk of cardiovascular
      death, ischemic heart disease and cardiac failure. Caution should be exercised
      when first prescribing a beta-agonist for patients with cardiovascular disease. A
      potential mechanism for adverse effects with regular use of beta(2)-agonists is
      tachyphylaxis. Tachyphylaxis to the bronchodilator effects of long-acting beta(2)
      agonists can occur, but has been consistently demonstrated only for formoterol
      (eformoterol) a full agonist, rather than salmeterol, a partial agonist.
      Tachyphylaxis to protection against induced bronchospasm occurs with both full
      and partial beta(2)-agonists, and probably within a matter of days at most.
      Underlying airway responsiveness to directly acting bronchoconstricting agents is
      not increased when the bronchodilator effect of the regular beta(2)-agonist has
      been allowed to wear off, although there may be an increase in responsiveness to
      indirectly acting agents. While there has been speculation that underlying airway
      inflammation in asthma may be made worse by regular use of short-acting beta(2)
      agonists, in contradistinction, a number of studies have shown that long-acting
      beta(2)-agonists have positive anti-inflammatory effects. An Australian Cochrane
      Airways Group systematic review of the randomized, controlled trials of short
      acting beta-agonists found only minimal and clinically unimportant differences
      between regular use and use as needed. Regular short-acting treatment was better
      than placebo. However, a subsequent systematic review has found that regular use
      of long-acting beta-agonists had significant advantages over regular use of short
      acting beta-agonists. More studies and data are needed on the regular use of
      beta(2)-agonists in patients not taking inhaled corticosteroids, and in
      potentially vulnerable groups, such as the elderly and those with particular
      genotypes for the beta-receptor, who might be more prone to adverse effects.

PMID- 14719996
TI  - Pharmacotherapy of the ion transport defect in cystic fibrosis: role of
      purinergic receptor agonists and other potential therapeutics.
AB  - Cystic fibrosis (CF), is an autosomal recessive disease frequently seen in the
      Caucasian population. It is caused by mutations in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. CF is characterized by enhanced
      airway Na(+) absorption, mediated by epithelial Na(+) channels (ENaC), and
      deficient Cl(-) transport. In addition, other mechanisms may contribute to the
      pathophysiological changes in the CF lung, such as defective regulation of
      HCO(3)(-) secretion. In other epithelial tissues, epithelial Na(+) conductance is
      either increased (intestine) or decreased (sweat duct) in CF. CFTR is a cyclic
      AMP-regulated epithelial Cl(-) channel, and appears to control the activity of
      several other transport proteins. Accordingly, defective epithelial ion transport
      in CF is likely to be a combination of defective Cl(-) channel function and
      impaired regulator function of CFTR, which in turn is linked to impaired
      mucociliary clearance and development of chronic lung disease. As the clinical
      course of CF is determined primarily by progressive lung disease, novel
      pharmacological strategies for the treatment of CF focus on correction of the ion
      transport defect in the airways. In recent years, it has been demonstrated that
      activation of purinergic receptors in airway epithelia by extracellular
      nucleotides (adenosine triphosphate/uridine triphosphate) has beneficial effects
      on mucus clearance in CF. Activation of the dominant class of metabotropic
      purinergic receptors, P2Y(2) receptors, appears to have a 2-fold benefit on ion
      transport in CF airways; excessive Na(+) absorption is attenuated, most likely by
      inhibition of the ENaC and, simultaneously, an alternative Ca(2+)-dependent Cl(-)
      channel is activated that may compensate for the CFTR Cl(-) channel defect. Thus
      activation of P2Y(2) receptors is expected to lead to improved hydration of the
      airway surface liquid in CF. Furthermore, purinergic activation has been shown to
      promote other components of mucociliary clearance such as ciliary beat frequency
      and mucus secretion. Clinical trials are under way to test the effect of
      synthetic purinergic compounds, such as the P2Y(2) receptor agonist INS37217, on
      the progression of lung disease in patients with CF. Administration of these
      compounds alone, or in combination with other drugs that inhibit accelerated
      Na(+) transport and help recover or increase residual activity of mutant CFTR, is
      most promising as successful therapy to counteract the ion transport defect in
      the airways of CF patients.

PMID- 14719997
TI  - Pharmacotherapeutic management of pulmonary sarcoidosis.
AB  - Corticosteroids are the mainstay of treatment for sarcoidosis. Although the
      indications for medical therapy of sarcoidosis are controversial, standard
      therapy for symptomatic, progressive disease consists of corticosteroids. The
      British Thoracic Society concluded, with respect to systemic corticosteroids for
      the treatment of sarcoidosis, that some patients required no treatment, some
      required prednisone for control of symptoms, and others, with persistent disease,
      appeared to benefit from long-term corticosteroid therapy. Inhaled budesonide can
      be an effective treatment for lung sarcoidosis, with few adverse effects, when
      used in combination with oral systemic corticosteroids such as deflazacort
      administered in a tapered regimen for 6 months. A randomized controlled trial has
      also demonstrated the efficacy of 3 months of treatment with oral prednisolone in
      a tapered regimen followed by inhaled budesonide for 15 months in patients with
      early stage pulmonary sarcoidosis.Alternative drugs are required in chronic
      resistant sarcoidosis and/or in conditions where systemic corticosteroids are
      contraindicated. Immunosuppressive agents (chlorambucil, cyclophosphamide,
      methotrexate, cyclosporine, azathioprine), anticytokine agents (thalidomide,
      pentoxifylline), antimalarials (chloroquine, hydroxychloroquine), melatonin and
      monoclonal antibody (infliximab) have been used in such situations. Chlorambucil
      and cyclophosphamide have been used in anecdotal cases of pulmonary sarcoidosis
      as corticosteroid-sparing agents. However, their toxicity and neoplastic
      potential recommend prudence in patient selection. A comparison between
      combination therapy with cyclosporine and prednisone and prednisone alone has
      shown an increased prevalence of serious adverse effects with combined therapy
      with no between-group differences in treatment efficacy. The cost and toxicity of
      cyclosporine limit its use to patients in whom its efficacy has been proven. In
      patients with chronic or refractory disease, methotrexate, usually administered
      once a week as a single oral dose for at least 2 years, has resulted in a
      significant improvement in respiratory function, chest radiographs and
      extrapulmonary manifestations. In most patients, this treatment enabled
      discontinuation of corticosteroids. Azathioprine may be effective as a
      corticosteroid-sparing agent in the long-term treatment of sarcoidosis. The
      combination of prednisolone and azathioprine over a period of 2 years has induced
      long-lasting remission in patients with resistant sarcoidosis. Thalidomide at low
      doses is effective in selected cases of sarcoidosis with cutaneous and mild
      pulmonary involvement. Pentoxifylline alone or combined with low doses of
      corticosteroids has achieved significant improvement in respiratory function in
      patients with pulmonary sarcoidosis. Chloroquine and hydroxychloroquine have been
      shown to have a specific effect in cutaneous manifestations, neurological
      involvement and hypercalcemia associated with sarcoidosis. Infliximab has yielded
      good results in patients with chronic resistant pulmonary and extrapulmonary
      sarcoidosis resistant to corticosteroid and cytotoxic therapy. The effectiveness
      of melatonin in cutaneous and pulmonary sarcoidosis has also been confirmed in a
      single center.

PMID- 14719998
TI  - Antibiotic treatment of multidrug-resistant organisms in cystic fibrosis.
AB  - Respiratory tract infection with eventual respiratory failure is the major cause
      of morbidity and mortality in cystic fibrosis (CF). Infective exacerbations need
      to be treated promptly and effectively to minimize potentially accelerated
      attrition of lung function. The choice of antibiotic depends on in vitro
      sensitivity patterns. However, physicians treating patients with CF are
      increasingly faced with infection with multidrug-resistant isolates of
      Pseudomonas aeruginosa. In addition, innately resistant organisms such as
      Burkholderia cepacia complex, Stenotrophomonas maltophilia and Achromobacter
      (Alcaligenes) xylosoxidans are becoming more prevalent. Infection with
      methicillin-resistant Staphylococcus aureus (MRSA) is also a problem. These
      changing patterns probably result from greater patient longevity and increased
      antibiotic use for acute exacerbations and maintenance care. Multidrug-resistant
      P. aeruginosa infection may be treated successfully by using two antibiotics with
      different mechanisms of action. In practice antibiotic choices have usually been
      made on a best-guess basis, but recent research suggests that more directed
      therapy can be achieved through the application of multiple-combination
      bactericidal testing (MCBT). Aerosol delivery of tobramycin for inhalation
      solution achieves high endobronchial concentrations that may overcome bacterial
      resistance as defined by standard laboratory protocols. Resistance to colistin is
      rare and this antibiotic should be seen as a valuable second-line drug to be
      reserved for multidrug-resistant P. aeruginosa. The efficacy of new antibiotic
      groups such as the macrolides needs to be evaluated.CF units should adopt strict
      segregation policies to interrupt person-to-person spread of B. cepacia complex.
      Treatment of panresistant strains is difficult and often arbitrary. Combination
      antibiotic therapy is recommended, usually tobramycin and high-dose meropenem
      and/or ceftazidime, but the choice of treatment regimen should always be guided
      by the clinical response.The clinical significance of S. maltophilia, A.
      xylosoxidans and MRSA infection in CF lung disease remains uncertain. If patients
      show clinical decline and are chronically colonized/infected with either of the
      former two pathogens, treatment is recommended but efficacy data are lacking.
      There are defined microbiological reasons for attempting eradication of MRSA but
      there are no proven deleterious effects of this infection on lung function in
      patients with CF. Various treatment protocols exist but none has been subject to
      a randomized, controlled trial. Multidrug-resistant microorganisms are an
      important and growing issue in the care of patients with CF. Each patient
      infected with such strains should be assessed individually and antibiotic
      treatment planned according to in vitro sensitivity, patient drug tolerance, and
      results of in vitro studies which may direct the physician to antibiotic
      combinations most likely to succeed.

PMID- 14719999
TI  - The dilemma of occupational rhinitis: management options.
AB  - Occupational rhinitis is a common heterogeneous group of inflammatory conditions
      in the nose, caused by exposure to airborne irritants and sensitizers in the
      occupational environment. The mechanism can be allergic, neurogenic or toxic.
      Data from several epidemiologic studies indicate that animal dander, organic
      dusts, latex and chemicals can cause occupational rhinitis, but because of
      methodological problems as well as weaknesses in the definition of occupational
      rhinitis, occupational exposure is probably an underestimated cause of rhinitis.
      The effect of rhinitis on the mental aspects of quality of life and substantial
      costs due to loss of productivity make it important to diagnose and treat
      occupational rhinitis. Diagnosis relies on a history of exposure, skin prick
      testing and, if possible, nasal provoacation. Avoidance of exposure, protective
      measures at the workplace and medical treatment, with agents such as second
      generation antihistamines and nasal corticosteroids, can make it possible to
      avoid progress of the disease from rhinitis to asthma. The efficacies of
      montelukast, a leukotrienne receptor antagonist, and omalizumab, an anti
      immunoglobulin E monoclonal antibody in the treatment of occupational rhinitis
      are yet to be evaluated

PMID- 14720000
TI  - BiPAP ventilation as assistance for patients presenting with respiratory distress
      in the department of emergency medicine.
AB  - BACKGROUND: Noninvasive ventilatory support (NIVS) is intended to provide
      ventilatory assistance for a wide range of respiratory disturbances. The use of
      NIVS for treatment of respiratory distress may be applicable in the emergency
      department (ED). It may prevent endotracheal intubation and, likewise, may
      favorably influence the course of the patient's hospitalization, depending on the
      primary disease or ventilatory disturbance. OBJECTIVE: To evaluate the efficacy
      of bilevel positive airway pressure (BiPAP) ventilation in patients with acute
      respiratory distress presenting in the ED. METHODS: A prospective, uncontrolled,
      nonrandomized, nonblind study enrolled 30 patients. They were cooperative and
      hemodynamically stable, aged over 18 years, and presented with acute respiratory
      distress as defined by predetermined criteria. They were connected to a BiPAP
      machine through a face mask, using an initial pressure of 8/3 cm H(2)O, which was
      gradually raised to 12/7 cm H(2)O inspiratory positive airway pressure/expiratory
      positive airway pressure. Standard drugs, inhalation and oxygen therapies were
      administered as needed. The BiPAP was disconnected either upon relief of
      respiratory distress or on deterioration of the patient's condition. RESULTS: Of
      the 30 patients in the study, 19 had cardiogenic pulmonary edema, four had acute
      asthma, three had exacerbation of COPD, three had pneumonia and one had malignant
      pleural effusion. BiPAP was instituted subsequent to failure of standard
      therapies. Twenty-six patients were classified as responders to the BiPAP
      ventilation and four as nonresponders (three patients were intubated after 1 hour
      and one patient 24 hours, post BiPAP). The total length of stay (LOS) in the ED
      was 3-5 hours and the mean LOS in hospital was 4.1 +/- 1.5 days, versus 6.5 +/-
      1.2 days in LOS reports of similar patients in the same hospital during 1999, who
      did not undergo BiPAP ventilation. No other complications were observed.
      CONCLUSIONS: We found BiPAP ventilation simple, safe, effective and well
      tolerated by patients in respiratory distress. The rate of endotracheal
      intubation after successful BiPAP ventilation was low. In carefully selected
      patients with respiratory distress, BiPAP ventilation may successfully replace
      endotracheal intubation.

PMID- 14720001
TI  - Clinical efficacy of inhaler devices containing beta(2)-agonist bronchodilators
      in the treatment of asthma: cochrane systematic review and meta-analysis of more
      than 100 randomized, controlled trials.
AB  - BACKGROUND: A number of different inhaler devices are available to deliver
      beta(2)-adrenoceptor agonist (beta(2)-agonist) bronchodilators in asthma. These
      include hydrofluoroalkane or chlorofluorocarbon (CFC)-free propelled pressurized
      metered-dose inhalers (pMDIs), many dry powder inhalers and breath-actuated
      inhalers. OBJECTIVE: To determine the clinical efficacy of all available hand
      held inhaler devices compared with the standard CFC-containing pMDI for the
      delivery of short-acting beta(2)-agonist bronchodilators in nonacute asthma in
      both children and adults. METHODOLOGY: A systematic review and meta-analysis was
      carried out of all available randomized, controlled trials (RCTs) using the
      standard pMDI compared with any other hand-held inhaler device, delivering short
      acting beta(2)-agonist bronchodilators in patients with stable asthma. RESULTS:
      One hundred and eighteen RCTs were included in this review. No clinical
      differences were found between the standard CFC-containing pMDI and 12 other hand
      held inhaler devices for most outcome measures. We found no evidence of clinical
      differences between studies using either a 1 : 1 (pMDI: another inhaler) or a 2 :
      1 dosing ratio. CONCLUSIONS: In patients with stable asthma, short-acting beta(2)
      agonist bronchodilators in standard CFC-pMDIs are as effective as any other hand
      held inhaler device; therefore the cheapest available device that the patient is
      able to use should always be considered. Pharmaceutical companies should in
      future submit to regulatory authorities clinical outcome data (as opposed to in
      vitro data) in support of any dosing schedules greater than 1 : 1 when compared
      with the standard pMDI. Clinical effectiveness studies that use an intention-to
      treat analysis and report more patient-centered outcomes are required.

PMID- 14720002
TI  - The role of DOTS in tuberculosis treatment and control.
AB  - Directly Observed Therapy Shortcourse (DOTS) is composed of five distinct
      elements: political commitment; microscopy services; drug supplies; surveillance
      and monitoring systems and use of highly efficacious regimens; and direct
      observation of treatment. The difference in the way the term 'DOTS' as defined by
      WHO and interpreted by many observers has led to some misunderstanding. WHO
      generally uses the term to mean the five components of DOTS. But the word 'DOTS'
      is an acronym for Directly Observed Therapy Shortcourse. Many workers therefore
      interpret DOTS purely as direct supervision of therapy. DOTS is not an end in
      itself but a means to an end. In fact it has two purposes, to ensure that the
      patient with tuberculosis (TB) completes therapy to cure and to prevent drug
      resistance from developing in the community. The main criticism of DOTS rightly
      derives from the fact that some properly conducted randomized, controlled trials
      of directly observed therapy with or without the other components have shown no
      benefit from it. The problem is that it is impossible to design a study of modern
      directly observed therapy against the previous self-administered, poorly
      resourced programs. As soon as a study is implemented, the attention to patients
      in the control (non-directly observed therapy) arm inevitably improves from the
      previous non-trial service situation. What is of concern is that in some trials
      less than 70% cure rates were achieved even in the direct observation arm. With
      no new drugs or adjuvant treatment available to bring the length of treatment
      down to substantially less than 6 months, DOTS offers the best means we have at
      our disposal for TB control.

PMID- 14720003
TI  - The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases:
      implications for therapy.
AB  - The nuclear factor kappa B (NF-kappaB) transcription factor plays a key role in
      the induction of pro-inflammatory gene expression, leading to the synthesis of
      cytokines, adhesion molecules, chemokines, growth factors and enzymes. Results of
      studies in in vitro and in vivo models of inflammation and malignancy have also
      suggested central roles for NF-kappaB in programmed cell death, or apoptosis. NF
      kappaB plays a central role in a variety of acute and chronic inflammatory
      diseases. In the common lung diseases associated with a significant inflammatory
      component such as severe sepsis, acute lung injury, acute respiratory distress
      syndrome, cystic fibrosis and asthma, the pathogenic roles of NF-kappaB have been
      extensively investigated. In COPD, activation of NF-kappaB has been implicated in
      disease pathogenesis but its exact role is less clearly demonstrable in this
      heterogeneous patient population. However, the principal risk factor for COPD,
      cigarette smoking, is strongly associated with NF-kappaB activation. Activation
      of NF-kappaB has been demonstrated in mineral dust diseases and probably plays a
      role in the pathogenesis of these chronic illnesses. NF-kB also plays a variety
      of roles in lung cancer including resistance to chemotherapy, inhibition of
      tumorigenesis and inducing expression of antiapoptotic genes. The complex NF
      kappaB pathway offers a variety of potential molecular targets for
      chemotherapeutic intervention. A variety of agents aimed at modulating NF-kappaB
      activity are in various stages of investigation.

PMID- 14720004
TI  - Treatment of community-acquired lower respiratory tract infections during
      pregnancy.
AB  - The incidence of lower respiratory tract infection (LRTI) in women of child
      bearing age is approximately 64 per 1000 population. The spectrum of illness
      ranges from acute bronchitis, which is very common, through influenza virus
      infection and exacerbations of underlying lung disease, to pneumonia, which,
      fortunately is uncommon (<1.5% LRTI), but can be severe. Acute bronchitis is
      generally mild, self-limiting and usually does not require antibacterial therapy.
      Influenza virus infection in pregnant women has been recently related to
      increased hospitalization for acute cardiorespiratory conditions. At present, the
      safety of the newer neuraminidase inhibitors for the treatment of influenza virus
      infection has not been established in pregnancy and they are not routinely
      recommended. In influenza virus infection complicated by pneumonia, antibacterial
      agents active against Staphylococcus aureus and Streptococcus pneumoniae
      superinfection should be used. There are few data on infective complications of
      asthma or COPD in pregnancy. The latter is rare, as patients with COPD are
      usually male and aged over 45 years. Management is the same as for nonpregnant
      patients. The incidence and mortality of pneumonia in pregnancy is similar to
      that in nonpregnant patients. Infants born to pregnant patients with pneumonia
      have been found to be born earlier and weigh less than controls. Risk factors for
      the development of pneumonia include anemia, asthma and use of antepartum
      corticosteroids and tocolytic agents. Based on the few available studies, the
      main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae,
      Mycoplasma pneumoniae and viruses. Beta-Lactam and macrolide antibiotics
      therefore remain the antibiotics of choice in terms of both pathogen coverage and
      safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial
      pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in
      nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not
      definitely been associated with adverse clinical outcomes despite theoretical
      risks. Currently it is still the treatment of choice in PCP, where mortality
      remains high. In conclusion, there are few data specifically related to pregnant
      women with different types of LRTI. Where data are available, no significant
      differences compared with nonpregnant patients have been identified. In
      considering the use of any therapeutic agent or investigation in pregnant
      patients with LRTI, safety aspects must be carefully weighed against potential
      benefit. Otherwise, management strategies should not differ from those for
      nonpregnant patients. Further research in this area is warranted.

PMID- 14720005
TI  - Legionnaires' disease: update on epidemiology and management options.
AB  - Infection with Legionella spp. is an important cause of serious community- and
      hospital-acquired pneumonia, occurring sporadically and in outbreaks. Outbreaks
      of Legionnaires' disease have recently received considerable media attention, and
      some factors indicate that the problem will increase in future. Infection with
      Legionella spp. ranks among the three most common causes of severe pneumonia in
      the community setting, and is isolated in 1-40% of cases of hospital-acquired
      pneumonia. Underdiagnosis and underreporting are high. Only 2-10% of estimated
      cases are reported. Detection of a single case should not be considered an
      isolated sporadic event, but rather indicative of unrecognized cases. There are
      no clinical features unique to Legionnaires' disease; however, suspicion should
      be raised by epidemiologic information commensurate with the diagnosis and the
      presence of headache, confusion, hyponatremia, elevated creatine kinase and/or
      severe pneumonia. An arterial oxygen partial pressure <60mm Hg on presentation
      and progression of pulmonary infiltrates despite appropriate antibacterial
      therapy should always alert clinicians to this cause.Macrolides, fluoroquinolones
      and rifampin (rifampicin) are the most widely used drugs in treatment.
      Fluoroquinolones or azithromycin are the treatment of choice in immunosuppressed
      patients and those with severe pneumonia. Incorporation of the legionella urinary
      antigen test in emergency departments in hospitals and progressive improvement in
      this test will, in the near future, permit appropriate diagnosis and treatment of
      this frequent, sometimes severe, illness.

PMID- 14720006
TI  - Anti-interleukin-5 monoclonal antibodies: preclinical and clinical evidence in
      asthma models.
AB  - Descriptive studies have shown an association between eosinophils, interleukin
      (IL)-5 and pathophysiological processes in patients with atopic asthma. These
      observations have led to an interest in the eosinophil as the pathogenic cell
      responsible for many of the clinical features of asthma including symptoms of
      wheeze, shortness of breath and cough, along with the physiological events such
      as airway hyperresponsiveness (AHR) and changes in lung function. IL-5 is one of
      the key cytokines responsible for eosinopoiesis in the bone marrow, along with
      recruitment and survival of eosinophils in the tissues. In view of this, IL-5 has
      been an attractive target for the development of anti-IL-5 monoclonal antibodies,
      inhibiting its action. The results of preclinical studies are viewed as
      encouraging. Preclinical development involved studies in mice, guinea-pigs and
      cynomolgus monkeys, with conflicting results in terms of changes in blood and
      bronchoalveolar lavage eosinophils, AHR and pulmonary resistance. These may be
      attributed to interspecies differences and to the different models used.
      Monoclonal antibodies directed against IL-5 have been used in at least four
      studies involving patients with asthma. Those preliminary studies have shown
      clear reductions in both blood and sputum eosinophils but no significant changes
      in physiological parameters of AHR, the late asthmatic reaction or in lung
      function or symptoms. As in the animal studies, these results suggest a
      dissociation between eosinophils, AHR, lung function and symptoms of asthma,
      which may be explained by the multitude of cells involved in the pathogenesis of
      asthma.

PMID- 14720007
TI  - Management of malignancy-associated pleural effusion: current and future
      treatment strategies.
AB  - Management of recurrent malignant pleural effusion, a common complication of
      malignancy, poses a challenge to clinicians. Although almost one century has
      elapsed since the introduction of the pleurodesis procedure, the ideal approach
      and best agent are still to be defined. Optimally, pleurodesis should be done at
      the bedside with a minimally invasive procedure, and suitable agents to achieve
      pleural symphysis should be inexpensive, available worldwide and free of adverse
      effects. To date, no substance completely fulfills these requirements. Silver
      nitrate should be considered for pleurodesis because of its low cost and ease of
      handling. Although talc has been used most frequently to induce pleurodesis,
      reports of death due to acute respiratory failure have raised concerns about the
      safety of this agent. Tetracycline, an effective alternative used in the past, is
      no longer commercially available. This agent has been substituted with
      derivatives of tetracycline, such as minocycline and doxycycline with success
      rates similar to those with tetracycline. Several antineoplastic agents have been
      injected into the pleural space with the aim of producing pleural symphysis, the
      most representative of this group being bleomycin. Recent knowledge of the
      molecular mechanisms involved in pleural inflammation has brought into focus new
      substances, such as transforming growth factor beta and vascular endothelial
      growth factor, which may be used as pleurodesis agents in the future.
      Nevertheless, more studies are necessary to better define the potential of these
      substances in the induction of pleural symphysis.Ideally, a sclerosing agent
      should be cost-effective, available worldwide and easily administered. Talc will
      probably stand as the preferred agent to be used for pleurodesis in malignant
      pleural effusion because of its efficacy, easy manipulation and handling.
      However, further investigation is necessary to minimize adverse effects related
      to talc.

PMID- 14720008
TI  - Combination therapy with single inhaler budesonide/formoterol compared with high
      dose of fluticasone propionate alone in patients with moderate persistent asthma.
AB  - BACKGROUND: The efficacy and safety of Symbicort (budesonide and formoterol in a
      single inhaler) were compared with those of a high dose of the commonly used
      corticosteroid fluticasone propionate in patients with moderate persistent
      asthma. METHODS: This randomized, double-blind, double-dummy, parallel-group
      study involved 373 patients with asthma (mean age 42 years; FEV(1) 78% of
      predicted; reversibility 21%). After a 2-week run-in period, during which
      patients received budesonide 200 microg twice daily, they were randomly assigned
      to treatment with either Symbicort Turbuhaler (budesonide/formoterol 160/4.5
      microg, one inhalation twice daily) or Flovent/Flixotide Diskus (fluticasone
      propionate 250 microg twice daily) for 12 weeks. RESULTS: Significantly greater
      increases in morning PEF, the primary efficacy variable, were observed in
      patients treated with budesonide/formoterol compared with fluticasone propionate
      (27.4 L/min vs 7.7 L/min; p < 0.001). Evening PEF and clinic FEV(1) also favored
      budesonide/formoterol compared with fluticasone propionate (p < 0.001), as did
      use of reliever medication (p = 0.04) and the proportion of reliever-free days (p
      < 0.001). There were also numerical improvements in symptom-free days (60.4% vs
      55.5%), night-time awakenings (7.9% vs 9.6%) and asthma-control days (57.8% vs
      52.4%) in favor of budesonide/formoterol. The risk of an exacerbation was reduced
      by 32% in the budesonide/formoterol group compared with the fluticasone
      propionate group (p < 0.05). Both treatments were well tolerated. CONCLUSION:
      Symbicort (budesonide/formoterol in a single inhaler) was more effective than a
      high dose of fluticasone propionate in improving lung function, reducing use of
      reliever medication and improving control of moderate persistent asthma.

PMID- 14720010
TI  - Acute asthma in children and adolescents: should inhaled anticholinergics be
      added to beta(2)-agonists?
AB  - Children and adolescents experiencing acute exacerbations of asthma benefit from
      the use of beta(2)-adrenoceptor agonists (beta(2)-agonists) and systemic
      corticosteroids. However, there have been conflicting reports regarding the
      efficacy of inhaled anticholinergic agents. This article summarizes the evidence
      provided by randomized controlled trials studying the efficacy of adding inhaled
      anticholinergic agents to beta(2)-agonists in nonhospitalized children and
      adolescents with acute exacerbations of asthma. This systematic review of
      randomized controlled trials suggests that the addition of inhaled
      anticholinergic agents to beta(2)-agonists is beneficial in children and
      adolescents, particularly those with severe exacerbations of asthma. When given
      in repeated doses, the addition of inhaled anticholinergic agents to beta(2)
      agonists improves lung function and reduces the risk of hospital admission by
      25%. Several treatment regimens, namely ipratropium bromide (250 or 500 microg
      per dose) every 20-60 minutes for two to three doses have been tested with
      similar beneficial effects. The addition of a single dose of an inhaled
      anticholinergic agent to beta(2)-agonists improves lung function but does not
      prevent hospital admission. The review did not identify any beneficial effects of
      anticholinergic agents in children with nonsevere asthma. Use of anticholinergic
      agents was not associated with increase in the incidence of nausea, vomiting or
      tremor. In conclusion, the addition of repeated doses of an inhaled
      anticholinergic agent to inhaled beta(2)-agonist is indicated in the emergency
      room management of children and adolescents with acute asthma, particularly those
      with severe exacerbations.

PMID- 14720011
TI  - Clinical implications of gastroesophageal reflux disease and swallowing
      dysfunction in COPD.
AB  - The intimate anatomical and physiologic relationship between the upper airway and
      esophagus consists of complex interactions between various muscles and nerves
      with both voluntary and involuntary patterns of control. Alterations in this
      harmonic relationship can lead to swallowing abnormalities ranging from dysphagia
      to gross aspiration, gastroesophageal reflux disease (GERD) and chronic cough.
      There is a paucity of data regarding pathologic alterations in the upper airway
      esophageal relationship in patients with COPD. The association between GERD and
      respiratory symptoms is well recognized in the setting of asthma; however, the
      nature of this relationship remains controversial. The association of GERD and
      COPD is even less clear. A review of the limited data on GERD and swallowing
      abnormalities in patients with COPD indicate that prevalence of GERD and
      esophageal disorders in patients with COPD is higher than in the normal
      population. However, its contribution to respiratory symptoms, bronchodilator use
      and pulmonary function in patients with COPD remains unknown. Although dysphagia
      and swallowing dysfunction on videofluoroscopic swallow evaluation are common in
      patients with COPD, their role as exacerbators of COPD remains to be elucidated.
      Further clinical research is necessary to evaluate the role of GERD and
      swallowing dysfunction in both stable and acute exacerbation of COPD.

PMID- 14720012
TI  - Prostanoids for pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a severe condition that markedly reduces
      exercise capacity and survival in the affected patient population. PAH includes
      primary pulmonary hypertension (PPH) and pulmonary hypertension associated with
      collagen vascular diseases, congenital systemic-to-pulmonary shunts, portal
      hypertension and HIV infection. All these conditions share virtually identical
      obstructive pathologic changes of the pulmonary microcirculation and probably
      similar pathobiologic processes. The pathophysiology is characterized by a
      progressive increase in pulmonary vascular resistance, leading to right
      ventricular failure and death. Prostacyclin is an endogenous substance that is
      produced by vascular endothelial cells and induces vasodilatation, inhibition of
      platelet activity, and antiproliferative effects. A dysregulation of prostacyclin
      metabolic pathways has been shown in patients with PAH and this represents the
      rationale for the exogenous therapeutic administration of this substance. The
      clinical use of prostacyclin in patients with PAH has been made possible by the
      synthesis of stable analogs that possess different pharmacokinetic properties but
      share similar pharmacodynamic effects. Experience in humans has been initially
      collected with epoprostenol, which is a synthetic salt of prostacyclin.
      Epoprostenol has a short half-life in the circulation and requires continuous
      administration by the intravenous route by means of infusion pumps and permanent
      tunnelized catheters. In addition, epoprostenol is unstable at room temperature,
      and the complex delivery system required is associated with several adverse
      effects and potentially serious complications. For these reasons, alternatives to
      intravenous epoprostenol have been sought and this has led to the development of
      analogs that can be administered subcutaneously (treprostinil), orally (beraprost
      sodium) or by inhalation (iloprost). Three unblinded clinical trials and several
      uncontrolled trials have shown that treatment with epoprostenol improved symptoms
      and exercise capacity in New York Heart Association (NYHA) class III and IV PAH
      patients and also survival in patients with PPH. Subcutaneous treprostinil
      improved symptoms, exercise, hemodynamics and clinical events in the largest
      clinical trial ever performed in PAH, but local infusion site reactions limited
      efficacy in a proportion of patients. Oral beraprost sodium improved exercise
      capacity only in patients with PPH and is the only prostacyclin analog that has
      also been tested in NYHA class II patients. Inhaled iloprost has improved
      symptoms, exercise capacity and clinical events in patients with PAH and
      inoperable chronic thromboembolic pulmonary hypertension. The favorable effects
      of prostanoids observed in all studies coupled with different profiles of adverse
      events and tolerability for each prostacyclin analog allow the unique opportunity
      to select the most appropriate compound for the individual patient with PAH.

PMID- 14720013
TI  - Recent advances in the management of asthma using leukotriene modifiers.
AB  - Asthma is a chronic inflammatory disease of the airways that affects
      approximately 100 million people worldwide. In order to reduce symptoms, improve
      pulmonary function, and decrease morbidity, current treatment guidelines
      emphasize the importance of controlling the underlying inflammation in patients
      with asthma. Leukotrienes are leukocyte-generated lipid mediators that promote
      airway inflammation. Recognition of the importance of leukotrienes in the
      pathogenesis of asthma has led to the development of leukotriene modifiers, the
      first new class of drugs for the treatment of asthma to become available in 25
      years. Controlled clinical trials with the four currently used leukotriene
      modifiers (montelukast, zafirlukast, and zileuton in the US and pranlukast in
      Japan) have established their efficacy in improving pulmonary function, reducing
      symptoms, decreasing night-time awakenings, and decreasing the need for rescue
      medications. They exert anti-inflammatory effects that attenuate cellular
      infiltration and bronchial hyperresponsiveness and complement the anti
      inflammatory properties of inhaled corticosteroids. In patients with moderate and
      severe asthma, they permit tapering of the corticosteroid dose. In patients with
      exercise-induced asthma, leukotriene modifiers limit the decline in and quicken
      the recovery of pulmonary functions without the tolerance issues seen with
      chronic long-acting beta(2)-adrenoceptor agonist use. In patients with aspirin
      (acetylsalicylic acid)-induced asthma, they improve pulmonary function and shift
      the dose response curve to the right, reducing the patient's response to aspirin.
      In patients with seasonal allergic rhinitis, with or without concomitant asthma,
      they improve nasal, eye, and throat symptoms as well as quality of life.
      Leukotriene modifiers are generally safe and well tolerated with adverse effect
      profiles similar to that of placebo. The one safety issue raised with leukotriene
      modifiers, Churg-Strauss Syndrome, appears to be the unmasking of an already
      present syndrome that is manifested when the leukotriene modifiers permit
      corticosteroid doses to be reduced. Although current treatment guidelines
      recommend their use in patients with mild persistent asthma, these guidelines
      were developed just as leukotriene modifiers were coming to the market, before
      much of the clinical efficacy data were published. Because asthma is a
      heterogeneous disease, the different asthma phenotypes respond differently to
      therapies; consequently asthma therapy needs to be individualized. Leukotriene
      modifiers increase the therapeutic options for patients with asthma and, based on
      recent data, it is expected that future guidelines will describe expanded uses
      for these agents in clinical circumstances where these drugs are effective.

PMID- 14720014
TI  - Recent developments in the treatment of obstructive sleep apnea.
AB  - Modern sleep medicine has been in existence for only 20 years and therefore has
      to be regarded as a comparatively recent field of specialization. For this reason
      it is not surprising that there are numerous new trends and developments
      concerning the treatment of sleep-related breathing disorders. This review
      focuses on developments in the treatment of obstructive sleep apnea (OSA) over
      the last 5 years.The review is based on a Medline bibliographic search using the
      key words 'treatment', 'obstructive sleep apnea' and 'sleep-related breathing
      disorders' and covers papers published since 1997, including references in these
      articles. In respect to conservative treatments the following important
      developments were found. Oral devices were shown to be effective in about 50-70%
      of patients with OSA, but at this stage it is not possible to predict in which
      patients successful treatment can be expected. As subjective compliance averages
      only about 50%, thermoplastic devices used as trial devices provide a reasonable
      alternative to reduce costs. Automatic continuous positive airway pressure (CPAP)
      units have been shown to cut costs when used for pressure titration in severe
      sleep apneics during the day or when used in so-called split-night procedures in
      appropriate cases. Nasal CPAP has proven to be effective in children, showing
      higher compliance rates than in adults. The development of mouth-pieces provides
      the possibility of using CPAP orally, e.g. after nasal surgery. Electrical
      stimulation of the tongue muscles shows promising preliminary results.
      Nevertheless, further research in this field is necessary. In the field of
      surgery, the most valuable development has been tissue reduction using
      radiofrequency energy, which has been shown to be effective and minimally
      invasive. Other fundamentally new surgical techniques have not been attempted
      within the last 5 years; instead, development in this area appears to be defined
      by a combination of previously known methods (so-called multilevel surgery) and
      optimized methods of patient selection. Such combined surgical procedures has
      achieved success rates of about 70%. Taking all these developments into account,
      CPAP therapy remains the gold standard for treatment of patients with OSA; yet
      the low long-term compliance rates of 60-70% have to be regarded as a major
      challenge warranting further effort.

PMID- 14720015
TI  - Eosinophilic bronchitis: clinical features, management and pathogenesis.
AB  - Eosinophilic bronchitis is a common and treatable cause of chronic cough. The
      major pathological feature is eosinophilic airway inflammation, similar to that
      seen in asthma. However, the associated airway dysfunction is quite different,
      with evidence of heightened cough reflex sensitivity, but no variable airflow
      obstruction or airway hyperresponsiveness. Recent evidence suggests that the
      differences in functional association are related to differences in localization
      of mast cells in airway wall, with airway smooth muscle infiltration occurring in
      asthma and epithelial infiltration in eosinophilic bronchitis. Diagnosis is
      usually made with induced sputum analysis after exclusion of other causes for
      chronic cough on clinical, radiological and lung function assessment. The cough
      responds well to inhaled corticosteroids but dose and duration of treatment
      remain unclear. Little is known about the natural history of this condition.
      However, some patients with COPD without a history of previous asthma have sputum
      eosinophilia, so one possibility is that some cases of eosinophilic bronchitis
      may develop fixed airflow obstruction. Further study of this interesting
      condition will increase our understanding of airway inflammation and airway
      responsiveness, leading to novel targets for therapeutics for both eosinophilic
      bronchitis and asthma.

PMID- 14720016
TI  - Clarithromycin extended-release tablet: a review of its use in the management of
      respiratory tract infections.
AB  - Clarithromycin is an orally active, advanced-generation macrolide that has been
      reformulated as an extended-release tablet (Biaxin) XL Filmtab allowing
      convenient once-daily administration. The reformulation is intended to improve
      patient compliance and the tolerability of the drug. Although maximum plasma
      clarithromycin concentrations are lower and reached later with the extended
      release tablets than with the immediate-release tablets, the two formulations are
      bioequivalent with respect to the area under the plasma concentration-time curve.
      Bioequivalence is also achieved between the formulations for the
      microbiologically active metabolite, 14-hydroxy-clarithromycin. Two randomized
      trials in patients with acute exacerbations of chronic bronchitis (AECB) showed
      that a 7-day course of clarithromycin extended-release 1000 mg once daily
      produced clinical cure rates of 83% and 85% and bacteriologic cure rates of 86%
      and 92% at the test-of-cure study visit. Similar rates of cure were achieved with
      a 7-day course of twice-daily clarithromycin immediate-release and with a 10-day
      course of twice-daily amoxicillin/clavulanic acid.A 7-day course of
      clarithromycin extended-release 1000 mg once daily produced clinical and
      bacteriologic cure rates of 88% and 86%, respectively, in patients with community
      acquired pneumonia (CAP). Similar cure rates were achieved in recipients of once
      daily levofloxacin in the same trial. In patients with acute maxillary sinusitis,
      a 14-day course of either once-daily clarithromycin extended-release or twice
      daily clarithromycin immediate-release produced statistically equivalent clinical
      cure rates of 85% and 79%, respectively. Both treatment groups achieved similar
      rates of radiographic success and resolution of sinusitis. Recent results
      indicate that clarithromycin extended-release 500 mg once daily for 5 days is
      also effective in the treatment of patients with streptococcal
      pharyngitis/tonsillitis and in the treatment of AECB. The most frequently
      reported drug-related events with clarithromycin extended-release were abnormal
      taste (7% incidence), diarrhea (6%) and nausea (3%). Most adverse drug reactions
      were of a mild and transient nature. In comparative clinical trials,
      clarithromycin extended-release had an improved gastrointestinal tolerability
      profile compared with the immediate-release formulation. In addition,
      clarithromycin extended-release was better tolerated than amoxicillin/clavulanic
      acid and as well tolerated as levofloxacin. Further studies are required to
      assess the cost-effectiveness ratio of clarithromycin relative to comparator
      antibacterial agents. CONCLUSION: Clarithromycin extended-release is an effective
      treatment for AECB, CAP, acute maxillary sinusitis, and pharyngitis (although not
      approved for the latter in the US), and is administered in a convenient dosage
      regimen that has the potential to encourage good compliance. The reformulation
      modulates clarithromycin absorption kinetics thereby improving tolerability.
      Therefore, clarithromycin extended-release provides a useful option for the
      treatment of specific respiratory tract infections.

PMID- 14720017
TI  - Psychiatric factors in asthma: implications for diagnosis and therapy.
AB  - Emotional factors are an obstacle in the diagnosis and management of asthma. This
      review discusses three problem patterns: negative emotions in relatively normal
      patients with asthma; patients presenting possible functional symptoms and;
      patients presenting asthma in conjunction with psychiatric deviations. Negative
      emotions influence the symptoms and management of asthma, even in relatively
      normal patients. Psychogenic symptoms appear normal, but culminate in functional
      symptoms in a minority of patients. Diagnosing and treating asthma in patients
      with comorbid asthma and psychiatric symptoms is very difficult. On the one hand,
      treating asthma may often be just treating the emotions. On the other hand,
      negative emotions make the treatment of asthma guesswork. Physicians should
      estimate emotional influences in their patients' symptoms for an optimal
      evaluation of medication efficacy. Assessment and analysis of emotional factors
      surrounding exacerbations seems essential, e.g. emotional precipitants of asthma
      and asthma-evoked negative emotions. Moreover, patients should be informed about
      stress-induced breathlessness and the consequences of overuse of bronchodilators.
      When patients present with atypical symptoms, or do not properly respond to
      asthma medication, functional symptoms should be suspected. Psychiatric analysis
      may often lead to the conclusion that symptoms have a functional basis. In
      patients with comorbid asthma and anxiety disorders, asthma should be the focus
      for treatment since difficult-to-control asthma often causes anxiety problems in
      the first place. Moreover, panic-like symptoms in asthma are often related to
      sudden onset asthma exacerbations. However, in patients with comorbid asthma and
      depression, depression should become the focus of treatment. The reason is that
      optimal treatment of depressive asthmatics is probably impossible. Special issues
      include specific problems with children, compliance problems, and physicians'
      dilemmas regarding the simultaneous treatment of asthma and psychiatric symptoms.

PMID- 14720018
TI  - Clinical usefulness of inflammatory markers in asthma.
AB  - Asthma is a significant and increasing health problem. Airway inflammation and
      hyperresponsiveness are key pathophysiological mechanisms underlying asthma.
      Currently, effective treatments target these two processes and can lead to
      clinically important improvements in disease control. At present, decisions to
      initiate or modify therapy are based on symptoms and measures of airway caliber,
      with no direct assessment of airway inflammation or hyperresponsiveness. It is
      now possible to measure airway inflammation using noninvasive markers such as
      exhaled gases, induced sputum and serum measurements. Exhaled nitric oxide (eNO)
      and induced sputum eosinophils show the greatest promise as clinically useful
      markers of airway inflammation in asthma. Induced sputum can now be applied to
      the diagnosis of airway diseases, based on its ability to detect eosinophilic
      bronchitis in cough, and to differentiate between eosinophilic and non
      eosinophilic asthma. The place of induced sputum and eNO in the ongoing
      monitoring of patients with asthma are now being investigated in controlled
      trials.

PMID- 14720019
TI  - Serotonin agonists and antagonists in obstructive sleep apnea: therapeutic
      potential.
AB  - Obstructive sleep apnea hypopnea syndrome (OSAHS) is a prevalent disorder
      associated with substantial cardiovascular and neurobehavioral morbidity. Yet
      this is a disorder for which there are no widely effective pharmacotherapies. The
      pathophysiology of obstructive sleep apnea namely, normal respiration in waking
      with disordered breathing only in sleep, suggests that this disorder should be
      readily amenable to drug therapy. Over the past 10 years, we have gained
      tremendous insight into the neurochemical mechanisms involved in state-dependent
      control of respiration. It is apparent from this work that there are many
      potential avenues for pharmacotherapies, including several seemingly conflicting
      directions for serotonergic therapies. Serotonin delivery is reduced to upper
      airway dilator motor neurons in sleep, and this contributes, at least in part, to
      sleep-related reductions in dilator muscle activity and upper airway obstruction.
      The dilator motor neuron post-synaptic serotonin receptors are 5-HT(2A) and 5
      HT(2C) subtypes, and in adults the presynaptic 5-HT receptor in motor nuclei is 5
      HT(1B), an inhibitory receptor. Serotonin receptors are also found within central
      respiratory neuronal groups, and these receptor subtypes include 5-HT(1A)
      (inhibitory) and 5-HT(2) receptors. Peripherally, stimulation of 5-HT(2A), 5
      HT(2C) and 5-HT(3) receptor subtypes have an inhibitory effect on respiration via
      action at the nodose ganglion. Many of these receptor subtypes and their signal
      transduction pathways may be affected by oxidative stress in obstructive sleep
      apnea. These alterations will make finding drug therapies for sleep apnea more
      challenging, but not insurmountable. Future directions are suggested for
      elucidating safe, well-tolerated serotonergic drugs for this disorder. Tryptophan
      was one of the first serotonergic drugs tested for OSAHS. This drug was withdrawn
      from the market as a result of reports linking tryptophan use with eosinophilic
      myalgia syndrome and life-threatening pulmonary hypertension. Newer drugs with
      serotonergic activity tested in persons with sleep-disordered breathing include
      buspirone, fluoxetine and paroxetine. Trials are presently being conducted to
      evaluate the effects of 5-HT(2A) and 5-HT(3) antagonists on OSAHS. Many of the
      drugs tested have not shown significant improvement in sleep apnea. However, with
      continued effort to elucidate the pharmacology of neurochemical control of state
      dependent changes in respiratory control, the availability of pharmacological
      therapy for this disorder is not too far away.

PMID- 14720020
TI  - Chlamydia pneumoniae infections in asthma: clinical implications.
AB  - Chlamydia pneumoniae is an intracellular pathogen that has been suggested to play
      a role in the pathology of asthma. However, so far none of the studies have
      provided clear evidence for a causative role of C. pneumoniae infections in
      asthma, although there is little doubt that chronic C. pneumoniae infection does
      aggravate asthma and should be treated. The diagnosis of C. pneumoniae infection
      is still a matter of concern for it is dependent on trained skilled personnel and
      can vary significantly between different diagnostic laboratories. This fact is
      also one of the major problems encountered when comparing epidemiological studies
      investigating the possible role of C. pneumoniae infections and their impact on
      the pathogenesis of other diseases. With regard to therapy, long-term treatment
      with macrolides is the best available method to eradicate C. pneumoniae.
      Successful therapy for C. pneumoniae, however, can also be complicated by the
      high possibility of de novo infection as epidemiological studies have shown that
      the prevalence of antibodies to C. pneumoniae increases with age in all
      populations studied. In the northern hemisphere the prevalence of C. pneumoniae
      is also affected by seasonal conditions. It is too early to draw any conclusions
      from the equatorial belt countries. The available data on C. pneumoniae in
      tropical countries indicate a much faster infection rate during early adulthood
      with 100% serological prevalence at an age greater than 25 years. This data, if
      confirmed, would argue against C. pneumoniae causing asthma since the asthma
      prevalence in those countries does not increase in a parallel pattern. An
      alternative interpretation of most studies could be that the increased rate of C.
      pneumoniae infections in patients with asthma results from a modified
      susceptibility towards the microorganism, due to yet unknown changes of the host
      cell's physiology. It should be kept in mind that increased prevalence of C.
      pneumoniae infection is not restricted to asthma. Further studies are needed to
      understand the role of C. pneumoniae, especially of chronic infection, in the
      pathogenesis of inflammatory diseases with a specific focus on the effect that
      the microorganism triggers in the infected host cell. Only when we understand
      what C. pneumoniae does to its host cell will we be able to judge its impact on
      the overall status of an affected patient, and this knowledge will help us to
      develop a successful therapy.

PMID- 14720021
TI  - Optimizing treatment outcomes in severe community-acquired pneumonia.
AB  - Severe community-acquired pneumonia (CAP) is a life-threatening condition that
      requires intensive care unit (ICU) admission. Clinical presentation is
      characterized by the presence of respiratory failure, severe sepsis, or septic
      shock. Severe CAP accounts for approximately 5-35% of hospital-treated cases of
      pneumonia with the majority of patients having underlying comorbidities. The most
      common pathogens associated with this disease are Streptococcus pneumoniae,
      Legionella spp., Haemophilus influenzae, and Gram-negative enteric rods.
      Microbial investigation is probably helpful in the individual case but is likely
      to be more useful for defining local antimicrobial policies. The early and rapid
      initiation of empiric antimicrobial treatment is critical for a favorable
      outcome. It should include intravenous beta-lactam along with either a macrolide
      or a fluoroquinolone. Modifications of this basic regimen should be considered in
      the presence of distinct comorbid conditions and risk factors for specific
      pathogens. Other promising nonantimicrobial new therapies are currently being
      investigated. The assessment of severity of CAP helps physicians to identify
      patients who could be managed safely in an ambulatory setting. It may also play a
      crucial role in decisions about length of hospital stay and time of switching to
      oral antimicrobial therapy in different groups at risk. The most important
      adverse prognostic factors include advancing age, male sex, poor health of
      patient, acute respiratory failure, severe sepsis, septic shock, progressive
      radiographic course, bacteremia, signs of disease progression within the first 48
      72 hours, and the presence of several different pathogens such as S. pneumoniae,
      Staphylococcus aureus, Gram-negative enteric bacilli, or Pseudomonas aeruginosa.
      However, some important topics of severity assessment remain controversial,
      including the definition of severe CAP. Prediction rules for complications or
      death from CAP, although far from perfect, should identify the majority of
      patients with severe CAP and be used to support decision-making by the physician.
      They may also contribute to the evaluation of processes and outcomes of care for
      patients with CAP.

PMID- 14720022
TI  - Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis:
      a review of randomized, controlled trials.
AB  - For several years there has been discussion of whether first-line pharmacological
      treatment of allergic rhinitis should be antihistamines or intranasal
      corticosteroids. No well documented, clinically relevant differences seem to
      exist for individual nonsedating antihistamines in the treatment of allergic
      rhinitis. Likewise, the current body of literature does not seem to favor any
      specific intranasal corticosteroid. When comparing efficacy of antihistamines and
      intranasal corticosteroids in allergic rhinitis, present data favor intranasal
      corticosteroids. Interestingly, data do not support antihistamines as superior in
      treating conjunctivitis associated with allergic rhinitis. Safety data from
      comparative studies in allergic rhinitis do not indicate differences between
      antihistamines and intranasal corticosteroids. Combining antihistamines and
      intranasal corticosteroids in the treatment of allergic rhinitis does not provide
      additional beneficial effects to intranasal corticosteroids alone. Considering
      present data, intranasal corticosteroids seem to offer superior relief in
      allergic rhinitis, when compared with antihistamines.

PMID- 14720023
TI  - Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of
      rehospitalization and death in COPD patients.
AB  - INTRODUCTION: In patients with COPD who have recently been hospitalized for their
      disease, we examined whether treatment with inhaled corticosteroids without or
      with long-acting beta-adrenoceptor agonists (beta-agonists) reduced
      rehospitalization and mortality. STUDY DESIGN: Retrospective cohort analysis in
      the UK General Practice Research Database. METHODS: We compared rehospitalization
      for a COPD-related medical condition or death within 1 year after first
      hospitalization, in 3636 COPD patients receiving prescriptions for inhaled
      corticosteroids or long-acting beta-agonists compared with 627 reference patients
      with COPD who were prescribed short-acting bronchodilators only. RESULTS:
      Rehospitalization within a year occurred in 13.2% of the reference COPD patients,
      14.0% of users of long-acting beta-agonists only, 12.3% of users of inhaled
      corticosteroids only, and 10.4% of users of inhaled corticosteroids and long
      acting beta-agonists. Death within a year occurred in 24.3% of the reference COPD
      patients, 17.3% of users of long-acting beta-agonists only, 17.1% of users of
      inhaled corticosteroids only, and in 10.5% of users of inhaled corticosteroids
      and long-acting beta-agonists. In multivariate analyses the risk of
      rehospitalization or death was reduced by 10% in users of long-acting beta
      agonists only (NS), by 16% in users of inhaled corticosteroids only, and by 41%
      in users of combined inhaled corticosteroids and long-acting beta-agonists (both
      p < 0.05). CONCLUSION: Use of inhaled corticosteroids with/without long-acting
      beta-agonists was associated with a reduction of rehospitalization or death in
      COPD patients.

PMID- 14720024
TI  - Cefepime: a review of its use in the management of hospitalized patients with
      pneumonia.
AB  - Cefepime (Maxipime), Maxcef, Cepimax, Cepimex, Axepim, a parenteral fourth
      generation cephalosporin, is active against many organisms causative in
      pneumonia. Cefepime has in vitro activity against Gram-positive organisms
      including Staphylococcus aureus and penicillin-sensitive, -intermediate and 
      resistant Streptococcus pneumoniae similar to that of cefotaxime and ceftriaxone.
      Cefepime also has good activity against Gram-negative organisms, including
      Pseudomonas aeruginosa, similar to that of ceftazidime. Importantly, cefepime is
      stable against many of the common plasmid- and chromosome-mediated beta
      lactamases and is a poor inducer of AmpC beta-lactamases. As a result, it retains
      activity against Enterobacteriaceae that are resistant to third-generation
      cephalosporins, such as derepressed mutants of Enterobacter spp. Cefepime may be
      hydrolyzed by the extended-spectrum beta-lactamases produced by some members of
      the Enterobacteriaceae, but to a lesser extent than the third-generation
      cephalosporins. Monotherapy with cefepime 1 or 2g, usually administered
      intravenously twice daily, was as effective for clinical and bacteriological
      response as ceftazidime, ceftriaxone or cefotaxime monotherapy (1 or 2g two or
      three times daily) in a number of randomized, clinical trials in hospitalized
      adult, or less commonly, pediatric, patients with generally moderate to severe
      community-acquired or nosocomial pneumonia. More limited data indicated that
      monotherapy with cefepime 2g three times daily was also as effective in treating
      patients with nosocomial pneumonia as imipenem/cilostatin 0.5g four times daily,
      and when combined with amikacin, cefepime was as effective as ceftazidime plus
      amikacin. Patients with pneumonia who failed to respond to previous antibacterial
      therapy with penicillins or other cephalosporins responded to treatment with
      cefepime. Cefepime is generally well tolerated, with a tolerability profile
      similar to those of other parenteral cephalosporins. In clinical trials, the
      majority of adverse events experienced by cefepime recipients were mild to
      moderate and reversible. The most common adverse events with a causal
      relationship to cefepime reported in clinical trials included rash and diarrhea.
      Other, less common, adverse events included pruritus, urticaria, nausea, vomiting
      oral candidiasis, colitis, headache, fever, erythema and vaginitis. CONCLUSION:
      Cefepime is an established and generally well tolerated parenteral drug with a
      broad spectrum of antibacterial activity which, when administered twice daily,
      provides coverage of most of the pathogens that may be causative in pneumonia. In
      randomized clinical trials in hospitalized patients with generally moderate to
      severe community-acquired or nosocomial pneumonia, cefepime monotherapy exhibited
      good clinical and bacteriological efficacy. Cefepime may become a preferred
      antibacterial agent for infections caused by Enterobacter spp. With prudent use
      in order to prevent the emergence of resistant organisms, cefepime will continue
      to be a suitable option for the empiric treatment of pneumonia.

PMID- 14720025
TI  - Adult respiratory distress syndrome: do selective anticoagulants help?
AB  - The adult respiratory distress syndrome (ARDS) is a form of acute lung injury
      that is characterized by florid extravascular fibrin deposition. Thrombosis in
      the pulmonary vasculature and disseminated intravascular coagulation have also
      been observed in association with ARDS. Fibrin deposition does not occur in the
      normal lung but is virtually universal in acute lung injury induced by disparate
      insults. A large body of basic and preclinical evidence further implicates
      abnormalities of pathways of fibrin turnover in the pathogenesis of acute
      inflammation and fibrotic repair. Coagulation is locally upregulated in the
      injured lung, while fibrinolytic activity is depressed. These abnormalities occur
      concurrently and favor alveolar fibrin deposition. The systemic derangements of
      fibrin turnover in sepsis are similar to those that occur in the injured lung.
      Recent clinical trials demonstrate that interventions using selective
      anticoagulation can provide a mortality advantage and that selective
      anticoagulants differ in their ability to provide clinical benefit. Preclinical
      trials in primates with sepsis-induced ARDS now indicate that anticoagulant
      interventions that block the extrinsic coagulation pathway can protect against
      the development of pulmonary fibrin deposition as well as lung dysfunction and
      acute inflammation. These observations provide proof of principle that key steps
      in the coagulation cascade are appropriate therapeutic targets to prevent the
      development of acute lung injury in ARDS. Ongoing studies and prior publications
      also support the hypothesis that reversal of the fibrinolytic defect in ARDS
      could protect against the development of acute lung injury. In all, these studies
      suggest that fibrin deposition in the injured lung as well as abnormalities of
      coagulation and fibrinolysis are integral to the pathogenesis of ARDS. The
      ability of selective anticoagulants to effectively and safely alter clinical
      outcome in ARDS remains to be determined.

PMID- 14720026
TI  - Lung cancer screening: will the controversy extend to its cost-effectiveness?
AB  - Lung cancer is the second most common cancer and the leading cause of cancer
      related deaths in the US. It has been shown that when treated in its early
      stages, survival rates improve. Despite this, controversy remains regarding
      screening for the early detection of lung cancer, primarily because mortality
      reductions were not observed in the trials that studied chest x-ray and sputum
      cytology. Nevertheless, renewed interest in screening, due in part to better
      screening options, has prompted further research exploring the potential cost
      effectiveness of implementing lung cancer screening programs. This article
      provides a critical review of the literature of economic evaluations of lung
      cancer screening programs. The focus of this review is the methodology
      implemented in these studies. Based on an electronic search of the literature
      (Pubmed, Medline and CancerLit) from Sep 1988-Sep 2001, seven articles that
      quantified the cost-effectiveness of lung cancer screening programs were
      identified. For most of the studies, the cost-effectiveness aspect was a minor
      component with little or no description of the methods. Although some studies
      focused more on estimating the economic efficiency of screening, their
      methodology was weak and still not well documented. Only two studies implemented
      fully a cost-effectiveness analysis and provided the necessary level of detail.
      If consensus can be reached regarding the clinical benefit of lung cancer
      screening, future studies related to cost-effectiveness would have to be
      implemented on much sounder methodology. The publications reviewed do provide
      preliminary support for the economic efficiency of screening for lung cancer.

PMID- 14720027
TI  - Targeting cysteinyl leukotrienes in patients with rhinitis, sinusitis and
      paranasal polyps.
AB  - Leukotrienes have been known in the field of immunology since the 1930s. At that
      time they were referred to as the slow reacting substance of anaphylaxis. They
      were not, however, characterized until the 1980s, when they were noted to be
      formed during the breakdown of arachidonic acid by the enzyme 5-lipoxygenase. The
      leukotrienes consist of leukotriene (LT) A4, LTB4, LTC4, LTD4 and LTE4, so named
      because the molecule was originally isolated from leukocytes and therefore its
      carbon backbone contains three double bonds in series, which constitutes a trion.
      This structural information provided the key to the oxidative pathway of
      lipometabolism, known as the 5-lipoxygenase. Leukotrienes are classified as
      inflammatory mediators, and therefore they are produced by a number of cell
      types, particularly mast cells, eosinophils, basophils, macrophages and
      monocytes. With the identification of asthma, allergic rhinitis and paranasal
      sinusitis associated with inflammatory pathways, the leukotrienes have been
      implicated in the pathogenesis of these conditions and have become targets for
      therapeutic modulation. Leukotriene synthesis inhibitors have been used
      successfully in the treatment of patients with asthma where they have
      demonstrated the ability to induce bronchial dilatation, provide protection
      against broncho-provocation tests and significantly diminish symptoms. When it
      was serendipitously noted that patients who had concomitant nasal pathology also
      showed improvement, leukotriene synthesis inhibitors were used as adjuvant
      therapy in the management of patients with rhinitis, sinusitis and nasal
      polyposis. Preliminary studies have demonstrated improvements in nasal airflow
      and reduced recurrence of nasal polyps as noted by endoscopy and imaging studies.
      Leukotriene synthesis inhibitors therefore appear to be a novel treatment
      modality for patients with rhinitis, sinusitis and nasal polyps when used as
      adjunctive therapy.

PMID- 14720028
TI  - Management of respiratory failure in status asthmaticus.
AB  - Status asthmaticus is a life-threatening episode of asthma that is refractory to
      usual therapy. Recent studies report an increase in the severity and mortality
      associated with asthma. In the airways, inflammatory cell infiltration and
      activation and cytokine generation produce airway injury and edema,
      bronchoconstriction and mucus plugging. The key pathophysiological consequence of
      severe airflow obstruction is dynamic hyperinflation. The resulting hypoxemia,
      tachypnea together with increased metabolic demands on the muscles of respiration
      may lead to respiratory muscle failure. The management of status asthmaticus
      involves intensive pharmacological therapy particularly with beta-adrenoceptor
      agonists (beta-agonists) and corticosteroids. Albuterol (salbutamol) is the most
      commonly used beta2-selective inhaled bronchodilator in the US. Epinephrine
      (adrenaline) or terbutaline, administered subcutaneously, have not been shown to
      provide greater bronchodilatation compared with inhaled beta-agonists.
      Corticosteroids such as methylprednisolone should be administered early.
      Aerosolized corticosteroids are not recommended for patients with status
      asthmaticus. Inhaled anticholinergic agents may be useful in patients refractory
      to inhaled beta-agonists and corticosteroids. In patients requiring mechanical
      ventilation, the strategy aims to avoid dynamic hyperinflation by enhancing
      expiratory time to allow complete exhalation. Complications of dynamic inflation
      are hypotension and barotrauma. Sedation with opioids, benzodiazepines or
      propofol is required to facilitate ventilator synchrony but neuromuscular
      blockade should be avoided as myopathy has been a reported complication. Overall,
      in the management of patients with status asthmaticus, the challenge to the
      pulmonary/critical care clinician is to provide optimal pharmacological and
      ventilatory support and avoid the adverse consequences of dynamic hyperinflation.

PMID- 14720029
TI  - Surfactant therapy for respiratory distress syndrome in premature neonates: a
      comparative review.
AB  - Exogenous surfactant therapy has been part of the routine care of preterm
      neonates with respiratory distress syndrome (RDS) since the beginning of the
      1990s. Discoveries that led to its development as a therapeutic agent span the
      whole of the 20th century but it was not until 1980 that the first successful use
      of exogenous surfactant therapy in a human population was reported. Since then,
      randomized controlled studies demonstrated that surfactant therapy was not only
      well tolerated but that it significantly reduced both neonatal mortality and
      pulmonary air leaks; importantly, those surviving neonates were not at greater
      risk of subsequent neurological impairment. Surfactants may be of animal or
      synthetic origin. Both types of surfactants have been extensively studied in
      animal models and in clinical trials to determine the optimum timing, dose size
      and frequency, route and method of administration. The advantages of one type of
      surfactant over another are discussed in relation to biophysical properties,
      animal studies and results of randomized trials in neonatal populations. Animal
      derived exogenous surfactants are the treatment of choice at the present time
      with relatively few adverse effects related largely to changes in oxygenation and
      heart rate during surfactant administration. The optimum dose of surfactant is
      usually 100 mg/kg. The use of surfactant with high frequency oscillation and
      continuous positive pressure modes of respiratory support presents different
      problems compared with its use with conventional ventilation. The different
      components of surfactant have important functions that influence its
      effectiveness both in the primary function of the reduction of surface tension
      and also in secondary, but nonetheless just as important, role of lung defense.
      With greater understanding of the individual surfactant components, particularly
      the surfactant-associated proteins, development of newer synthetic surfactants
      has been made possible. Despite being an effective therapy for RDS, surfactant
      has failed to have a significant impact on the incidence of chronic lung disease
      in survivors. Paradoxically the cost of care has increased as surviving neonates
      are more immature and consume a greater proportion of neonatal intensive care
      resources. Despite this, surfactant is considered a cost-effective therapy for
      RDS compared with other therapeutic interventions in premature infants.

PMID- 14720031
TI  - Persistent abnormal lung function after childhood empyema.
AB  - OBJECTIVE: The purpose of this study was to examine pulmonary function tests in
      children at various time points in their recovery from empyema. DESIGN: Cross
      sectional study. SETTING: Academic Children's Hospital. PATIENTS: Pediatric
      patients with a diagnosis of empyema between 1992-2000. RESULTS: A total of 45
      pulmonary function tests were carried out in 36 study participants. Within 3
      months of hospital discharge, 91% of pulmonary function tests demonstrated a
      restrictive pattern with a mean forced vital capacity (FVC) of 69.2 +/- 4% and a
      mean total lung capacity (TLC) of 74.9 +/- 4% of predicted. The incidence of
      restriction in pulmonary function significantly decreased over time and for
      patients tested > 1 year from hospital discharge the mean FVC was 87.1 +/- 2% and
      the mean TLC 95.0 +/- 2% of predicted. However, 19% of the patients tested > 1
      year from discharge demonstrated a mild restrictive pattern and 16% demonstrated
      a mild obstructive changes. Patients with abnormal lung function > 1 year from
      hospital discharge did not demonstrate any signs or symptoms of respiratory
      insufficiency . CONCLUSION: There is a high incidence of restrictive patterns in
      lung function for children tested within 3 months from hospital discharge for
      empyema. The incidence of restrictive patterns decreased significantly over time
      and most patients tested >1 year from hospital discharge demonstrated normal lung
      function.

PMID- 14720030
TI  - Impact of inhaled salmeterol/fluticasone propionate combination product versus
      budesonide on the health-related quality of life of patients with asthma.
AB  - OBJECTIVE AND DESIGN: Measurement of health-related quality of life (HR-QOL) may
      show benefits of asthma treatments not revealed by objective monitoring and can
      complement clinical and physiological assessments of treatment outcome. HR-QOL
      was measured in four countries in a multicenter, double-blind, randomized
      comparison of salmeterol/fluticasone propionate combination and budesonide in
      patients aged > or =12 years with moderate-to-severe asthma uncontrolled by
      inhaled corticosteroids. METHODS: Patients received, twice daily, either
      salmeterol/fluticasone propionate 50/250 microg (Seretide/ Advair) via Diskus
      inhaler (n = 55) or budesonide 800 microg (Pulmicort) via Turbuhaler (n = 58).
      Patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline
      and after 12 weeks treatment (or early withdrawal). The analysis included 113
      patients. RESULTS: Mean improvement in AQLQ scores achieved clinical importance
      in all four domains in the salmeterol/fluticasone group (AQLQ change > or =0.5),
      but in only two domains in the budesonide group. Although the mean overall
      improvement in AQLQ scores observed in the salmeterol/fluticasone group was
      significantly greater than that observed in the budesonide group (difference of
      0.45; p = 0.002), the difference was less than the minimal important difference
      (0.5). Nevertheless, further analysis showed that the number-needed-to-treat was
      only 3.4. This indicates that only 3.4 patients need to be treated with the
      salmeterol/fluticasone combination for one patient to experience a meaningful
      improvement in HR-QOL, relative to monotherapy with an increased dose of
      budesonide. CONCLUSION: Treatment of moderate-to-severe asthma with
      salmeterol/fluticasone propionate resulted in superior gains in HR-QOL relative
      to increasing the dose of inhaled corticosteroids.

PMID- 14720032
TI  - Opinion and evidence in respiratory medicine.

PMID- 14720033
TI  - Beta2-agonist eutomers: a rational option for the treatment of asthma?
AB  - Beta2-adrenoceptor agonists (beta2-agonists) such as albuterol (salbutamol) and
      terbutaline and their long-acting analogs salmeterol and formoterol are widely
      used as bronchodilators in the treatment of asthma. They are chiral drugs
      historically marketed as racemic mixtures of an active (eutomer) and essentially
      inactive (distomer) stereoisomer. Despite their obvious therapeutic value and
      widespread use, beta2-agonists have been implicated, somewhat controversially, in
      causing an increase in asthma mortality and a deterioration of asthma control by
      a mechanism that remains elusive. Inherent toxicity of the distomers has been
      widely touted as an explanation and has given rise to pressure for the
      replacement of the racemates with pure eutomer formulations (the so-called chiral
      or racemic switch). This has culminated in the recent introduction into clinical
      practice of the single active stereoisomer of albuterol (levalbuterol) and the
      promise of other pure beta2-agonist eutomer formulations to follow. This article
      examines the evidence on which these chiral switches are based. Clinical studies
      designed to reveal negative effects of beta2-agonists have searched for
      reductions in lung function, increases in airway responsiveness to
      bronchoconstrictor mediators and worsening of asthma control. Crossover studies
      administering the pure stereoisomers and racemate of albuterol have not shown a
      clear superiority of the pure eutomer formulation over the racemate in terms of
      either bronchial hyperresponsiveness, tachyphylaxis to bronchoprotective effects
      or improvements in lung function. Clinical toxicity of beta2-agonist distomers on
      any aspect of asthmatic lung function has also not been demonstrated in the
      relatively short-term inhalational studies (single dose or repeated dose studies
      <1 week) that have been carried out. In animal studies, the administration of
      beta2-agonist racemates and distomers has been shown to enhance bronchial
      hyperresponsiveness but only in ovalbumin-sensitized animals where the relevance
      to humans is questionable. The pharmacokinetics and metabolism of beta(2)-agonist
      stereoisomers appear to be essentially similar whether administered as single
      stereoisomers or as racemates. Levalbuterol may be slightly more potent than an
      equivalent dose given as racemate, but there is some evidence that it forms a
      small amount of the distomer in vivo which detracts somewhat from its purported
      benefits over use of the racemate. Whilst there remains a clear need for studies
      of longer duration with sensitive clinical endpoints to evaluate the benefits of
      beta2-agonist eutomers and to investigate distomer toxicity, the chiral switch
      for beta2-agonists in general, and for albuterol in particular, does not appear
      to be justified on the basis of the evidence available to date.

PMID- 14720034
TI  - Lung volume reduction surgery as a bridge to lung transplantation.
AB  - Lung volume reduction surgery (LVRS) improves lung function, exercise capacity,
      and quality of life in patients with advanced emphysema. In some patients with
      emphysema who are candidates for lung transplantation, LVRS is an alternative
      treatment option to lung transplantation, or may be used as a bridge to lung
      transplantation. Generally accepted criteria for LVRS include severe non
      reversible airflow obstruction due to emphysema associated with significant
      evidence of lung hyperinflation and air trapping. Both high resolution computed
      tomography (CT) scan of the chest and quantitative ventilation/perfusion scan are
      used to identify lung regions with severe emphysema which would be used as
      targets for lung resection. Bilateral LVRS is the preferred surgical approach
      compared with the unilateral procedure because of better functional outcome. Lung
      transplantation is the preferred surgical treatment in patients with emphysema
      with alpha1 antitrypsin deficiency and in patients with very severe disease who
      have homogeneous emphysema pattern on CT scan of the chest or very low diffusion
      capacity.

PMID- 14720035
TI  - Angiogenesis in non-small cell lung cancer. A new target for therapy.
AB  - Non-small cell lung cancer (NSCLC) is cured with surgery in a minority of
      affected persons. Chemotherapy and radiation can palliate and extend survival of
      patients with disease not amenable to surgery. Consequently, new treatment
      options are urgently needed. In the era of molecularly targeted therapeutics, the
      recent direction in cancer research has been to identify and modulate specific
      events in tumorigenesis. Angiogenesis, or new vessel formation, is one such event
      elucidated to be fundamental to the development, growth, and metastasis of
      cancers and is one of the characteristics that differentiates tumor from host.
      Thus, targeting of tumor neovasculature continues to generate tremendous
      enthusiasm and effort in drug development. Extensive research into the role of
      angiogenesis in NSCLC has produced a host of novel targets; their potential
      inhibitors, now numbering over 40, are in various phases of clinical testing
      around the world. The current lead compounds include inhibitors of matrix
      metalloproteinases, angiogenic growth factors and their receptor tyrosine
      kinases. Despite their impressive activity in animal models, definitive evidence
      of their antitumor activity in humans is yet to be established. We face several
      challenges as we look to advance the field of antiangiogenesis for the treatment
      of cancer, namely, the need for a better understanding of the optimal timing and
      dosing of antiangiogenic agents, the validation of imaging and quantification
      methods of tumor angiogenesis, and a new clinical trials design for a more
      expedient evaluation of novel cytostatic target modulators.

PMID- 14720036
TI  - Changing paradigms in the diagnosis and management of bronchiectasis.
AB  - The face of bronchiectasis may have changed in recent years but individual cases
      continue to pose difficult challenges. As childhood infection becomes less of a
      problem, alternative causes of bronchiectasis are increasingly recognized which
      themselves offer new problems of diagnosis and management. Evolving concepts of
      pathogenesis suggest alternative strategies for treatment but as yet the evidence
      base on which to make firm decisions is lacking. Antibacterial regimens are not
      universally applicable and individualized protocols with parenteral, nebulized or
      continuous antibacterial therapy are increasingly used in the treatment of
      patients with bronchiectasis. Despite the theoretical appeal of using mucolytic
      or anti-inflammatory drugs their roles are still uncertain and have yet to be
      examined in adequate clinical trials. The factors determining disease progression
      are still poorly understood but in some patients worsening airflow obstruction
      heralds the onset of ventilatory failure. The management of the latter requires
      bronchodilators and controlled oxygen therapy, and strategies including non
      invasive ventilation are increasingly an option. Changing indications for surgery
      are evident with fewer palliative resections but a developing role for
      transplantation.

PMID- 14720037
TI  - Current status of gene therapy for cystic fibrosis pulmonary disease.
AB  - Cystic fibrosis (CF) is a common lethal genetic disorder that affects all ethnic
      populations; however, it is most prevalent in Caucasians. Intensive basic
      research over the last 20 years has resulted in a wealth of information regarding
      the CF gene, its protein product and the mutational basis of disease. This
      increased understanding has lead to the development of gene therapy for the
      treatment of CF pulmonary disease. Delivery of the CF gene to the airway requires
      direct in vivo transfer using vectors encoding for normal CF transmembrane
      regulator (CFTR) protein. Several vectors are currently available for CF gene
      transfer and include both viral (adenoviruses, adeno-associated viruses) and non
      viral (liposomal) systems. Initial clinical trials with each of these vectors
      have demonstrated that gene transfer to the CF airway is possible. The efficiency
      of transfer and duration of expression, however, have been limited. The effects
      of gene transfer on correction of the basic ion transport defects have also been
      highly variable and inconsistent, irrespective of the vector. Currently, the risk
      of severe immunological reactions is the primary factor limiting the clinical
      advancement of gene therapy. Both the adenoviral and liposomal vectors are
      associated with significant acute inflammatory reactions. The adenoviruses and
      adeno-associated viruses also elicit humoral immune responses that significantly
      reduce the efficiency of transgene expression and increase the risk of
      readministration. Several strategies are under investigation to improve the
      efficiency of gene transfer to the CF airway. These include overcoming local
      barriers in the lung, circumventing the immune response and improving vector
      internalization and/or uptake. Application of gene transfer in the child and
      possibly the fetus are also potential future clinical applications of gene
      therapy. However, despite considerable research with gene therapy, there is
      little evidence to suggest that a well tolerated and effective gene transfer
      method is imminent and aggressive use of conventional pharmacological therapies
      currently offer the greatest promise in the treatment of patients with CF.

PMID- 14720038
TI  - Allergens in the pathogenesis of asthma: potential role of anti-immunoglobulin E
      therapy.
AB  - Evidence suggests that allergy is a significant triggering factor in asthma in
      children and adults alike. In immunoglobulin (Ig) E-mediated allergic reactions,
      sensitization occurs when allergen-specific B cells are stimulated and switched
      to IgE antibody production by interleukin (IL)-4 and IL-13 provided by helper T
      cells type 2 (Th2). The IgE antibodies act by arming cells bearing either the
      high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII or CD23) receptor. The
      subsequent interaction of allergen with IgE-FcepsilonRI complexes on mast cells
      and basophils causes cross-linking of receptors that triggers the release of a
      variety of inflammatory mediators, cytokines and chemokines. Therefore, the
      ability to lower circulating free IgE levels is desirable because most
      individuals are exposed to multiple allergens to which they are sensitive at any
      given time. Omalizumab (formerly known as rhuMAb-E25) is a recently developed
      humanized monoclonal anti-IgE antibody directed at the FcepsilonRI binding domain
      of human IgE. It inhibits binding of IgE to mast cells without provoking mast
      cell activation. Preliminary clinical data from randomized controlled trials have
      shown that the addition of omalizumab to standard asthma therapy reduces asthma
      exacerbations and decreases inhaled corticosteroid and rescue medication use. The
      compound is also well tolerated. Omalizumab represents a novel therapeutic
      approach in the management of asthma.

PMID- 14720039
TI  - Flunisolide HFA.
AB  - Flunisolide is a synthetic corticosteroid approved for the treatment of
      persistent asthma and delivered by means of a metered-dose inhaler (MDI). A new
      formulation of flunisolide, using hydrofluoroalkane (HFA) as a propellant, has
      been developed to comply with the mandated worldwide phase-out of ozone-depleting
      chlorofluorocarbon (CFC) propellants. Aerosol particle size in the new
      flunisolide HFA solution is smaller than the flunisolide CFC suspension (1.2 vs
      3.8 microm mass median aerodynamic diameter). Aerosol particle size is a key
      element in determining lung deposition and the regional distribution of inhaled
      medication within the lung. In addition, the flunisolide HFA MDI has been
      redesigned to include a built-in spacer. These features have improved distal lung
      deposition. Flunisolide HFA, at one-third the dosage (170 and 340 microg twice
      daily), had similar efficacy to flunisolide CFC (500 and 1000 microg twice daily)
      and significantly greater efficacy than placebo in a randomized, double-blind,
      placebo-controlled, 12-week study in patients with mild to moderate asthma.
      Flunisolide HFA was well tolerated in all trials. A long-term study found no
      suppression of adrenal function and minimal systemic effects were observed both
      in adults and children.

PMID- 14720043
TI  - Macrolides in cystic fibrosis: is there a role?
AB  - A spectrum of anti-inflammatory properties, evidence of anti-infective action
      against Pseudomonas aeruginosa at sub-inhibitory concentrations and positive
      clinical experience in patients with diffuse panbronchiolitis, a disease with
      features in common with cystic fibrosis (CF), has prompted research to evaluate
      the role of macrolide therapy in patients with CF. Newer macrolides such as
      azithromycin have the advantage of improved tolerability and a prolonged
      intracellular half-life requiring an infrequent dosing regimen. Results from
      initial studies suggest a benefit from several months of macrolide therapy in
      patients with CF. An improvement in lung function was initially shown in a small
      open study in children, while maintenance of lung function compared with placebo,
      reduced acute respiratory exacerbations, and reduced systemic markers of
      inflammation were demonstrated in a randomized, placebo-controlled study of
      macrolide therapy in adult patients with CF. Additional controlled studies are
      required to determine optimal drug, dosage, and duration of therapy, and long
      term adverse effects of prolonged therapy with macrolides in patients with CF.
      The potential, with long-term use, to induce resistance against other bacteria
      colonizing the upper respiratory tract e.g. pneumococci has not been explored.
      Measurement of cytokines and inflammatory mediators from the sputum of patients
      with CF is technically difficult and does not correlate with disease activity.
      There is a need for easily measurable, reproducible and clinically meaningful end
      points for evaluation of new therapies in CF. The choice of appropriate outcome
      measures, apart from lung function, to monitor disease activity needs careful
      consideration in clinical trials determining the efficacy of macrolides in
      patients with CF. Evidence-based recommendations for the use of macrolides in the
      treatment of CF are not expected for some years although macrolides are already
      being prescribed for long-term use in some centers. There is a need for further
      research into mechanisms of anti-inflammatory action of macrolides in the lungs
      of patients with CF and whether or not such therapy may be beneficial in the long
      term.

PMID- 14720044
TI  - The role of systemic corticosteroids in acute exacerbation of chronic obstructive
      pulmonary disease.
AB  - The administration of systemic corticosteroids for patients with exacerbations of
      chronic obstructive pulmonary disease (COPD) has become common practice over the
      past 25 years. This practice remained somewhat controversial because
      corticosteroids can have serious adverse effects and initial clinical trials
      provided inconclusive evidence concerning their efficacy. Results from recent
      clinical trials indicate that systemic corticosteroids are modestly effective in
      shortening the duration of severe exacerbations of COPD. Systemic corticosteroids
      administered intravenously or orally to hospitalized patients with exacerbations
      of COPD reduced the absolute treatment failure rate by about 10%, increased the
      forced expiratory volume in 1 second (FEV1) by about 100 ml, and shortened the
      hospital stay by 1 to 2 days. Oral corticosteroids probably confer similar
      benefits when used for treating moderately severe COPD exacerbations in an out
      patient setting. The optimal starting dose of corticosteroids is not known, but
      the duration of treatment should not extend longer than 2 weeks. Hyperglycemia is
      the most common adverse event, but secondary infections, mental disturbances, and
      myopathies may also occur.

PMID- 14720045
TI  - The role of defensins in lung biology and therapy.
AB  - Innate host defence, involving both cellular and humoral mediators, is a
      prominent function of the human airways. Cellular mediators of innate immunity
      include dendritic cells, natural killer cells, cytotoxic T cells, macrophages and
      neutrophils, while humoral mediators of innate immunity consist of components of
      the epithelial lining fluid (ELF) covering the airways. Microbicidal substances
      in the ELF can selectively disrupt bacterial cell walls and membranes, sequester
      microbial nutrients or act as decoys for microbial attachment. Antimicrobial
      components of airway secretions include lysozymes, lactoferrin, secretory
      leukoprotease inhibitor, defensins and cathelicidins. Defensins are the most
      widely studied family of antimicrobial peptides present in airway fluid. Humans
      produce at least 10 different defensin molecules, six alpha-defensins and four
      beta-defensins similar in structure and function. Direct evidence that defensins
      have central roles in host defense has only recently become available. Some
      defensins and defensin-like molecules could serve as templates for the
      development of pulmonary pharmaceuticals. As potential therapeutics, they possess
      several desirable properties, including the ability to kill a broad spectrum of
      micro-organisms while permitting little development of microbial resistance. Many
      peptides can also neutralize effects of lipopolysaccharide on macrophages and
      other host defense cells and decrease the release of proinflammatory cytokines
      thereby giving protection against septic shock. Protegrin-1 is a minidefensin
      isolated from pig leukocytes and has proved to be an attractive template for
      large-scale development of antibacterials. One such protegrin analog, iseganan is
      in phase III clinical trials for the treatment of oral mucositis secondary to
      systemic chemotherapy. Other prospective uses of iseganan include control of
      respiratory pathogens in patients with cystic fibrosis and reduction of oral
      bacteria to prevent ventilator-associated pneumonia. However, in order to advance
      the production and clinical testing of peptide-based therapeutics, technical
      hurdles of synthesizing large quantities of complexly folded peptides must be
      first overcome. Strategies to develop potent peptide-based microbicides are
      promising in the struggle against increasingly resistant pathogens.

PMID- 14720046
TI  - Delivering antibacterials to the lungs: considerations for optimizing outcomes.
AB  - An important determinant of clinical outcome of a lower respiratory tract
      infection may be sterilization of the infected lung, which is also dependent on
      sustained antibacterial concentrations achieved in the lung. For this reason,
      recently there has been increased interest in measuring the concentration of
      antimicrobial agents at different potential sites of infection in the lung.
      Levels of antibacterials are now measured in bronchial mucosa, epithelial lining
      fluid (ELF) and alveolar macrophages, as well as in sputum. Penicillins and
      cephalosporins reach only marginal concentrations in bronchial secretions,
      whereas fluoroquinolones and macrolides have been shown to achieve high
      concentrations. The extent of penetration of different antibacterials into the
      bronchial mucosa is relatively high. This is also true for beta-lactams, although
      their tissue concentrations never reach blood concentrations. Antibacterials
      penetrate less into the ELF than into the bronchial mucosa, but fluoroquinolones
      appear to concentrate more into alveolar lavage than into bronchial mucosa.
      Pulmonary pharmacokinetics is a very useful tool for describing how drugs behave
      in the human lung, but it does not promote an understanding of the
      pharmacological effects of a drug. More important, instead, is the correlation
      between pulmonary disposition of the drug and its minimum inhibitory
      concentration (MIC) values for the infectious agent. The addition of
      bacteriological characteristics to in vivo pharmacokinetic studies has triggered
      a 'pharmacodynamic approach'. Pharmacodynamic parameters integrate the
      microbiological activity and pharmacokinetics of an anti-infective drug by
      focusing on its biological effects, particularly growth inhibition and killing of
      pathogens. Drugs that penetrate well and remain for long periods at the pulmonary
      site of infection often induce therapeutic responses greater than expected on the
      basis of in vitro data. However, although the determination of antibacterial
      concentrations at the site of infection in the lung has been suggested to be
      important in predicting the therapeutic efficacy of antimicrobial treatment
      during bacterial infections of the lower respiratory tract, some studies have
      demonstrated that pulmonary bacterial clearance is correlated more closely to
      concentrations in the serum than to those in the lung homogenates, probably
      because they better reflect antibacterial concentration in the interstitial
      fluid.

PMID- 14720047
TI  - Inhaled salmeterol/fluticasone propionate combination in chronic obstructive
      pulmonary disease.
AB  - Salmeterol/fluticasone propionate is a fixed-dose combination of the long-acting
      beta2-adrenoceptor agonist salmeterol and the corticosteroid fluticasone
      propionate and is inhaled via the Diskus powder inhaler. In three randomized,
      double-blind, 24-week or 52-week studies in >2850 patients with chronic
      obstructive pulmonary disease (COPD), administration of salmeterol/fluticasone
      propionate 50/250 microg twice daily (in one study) and salmeterol/fluticasone
      propionate 50/500 microg twice daily (in the other studies) provided greater
      improvement in lung function than placebo or either component alone at the same
      nominal dosage. Both strengths of the combination product administered twice
      daily resulted in clinically meaningful increases in scores in health-related
      quality-of-life questionnaires that were specific for respiratory disease.
      Improvements in this and almost all other secondary measures of efficacy,
      including symptomatic outcomes, were significantly greater with the combination
      product than with placebo. Administration of salmeterol/fluticasone propionate as
      a combination product did not result in any untoward interactions that affected
      the pharmacodynamic, pharmacokinetic or tolerability profiles of the individual
      components. Candidiasis, hoarseness/dysphonia, throat irritation and headache
      occurred more frequently with salmeterol/fluticasone propionate than with placebo
      in patients with COPD.

PMID- 14720051
TI  - Formoterol: a review of its use in chronic obstructive pulmonary disease.
AB  - Inhaled formoterol is a long-acting selective beta2-adrenoceptor agonist, with an
      onset of action of 5 minutes postdose and a bronchodilator effect that lasts for
      at least 12 hours. Statistically significant and clinically relevant (>120 ml)
      improvements in lung function [assessed using standardized/normalized area under
      the forced expiratory volume in 1 second (FEV1) versus time curve (AUC FEV1)]
      were observed with inhaled formoterol 12 microg twice daily (the approved dosage
      in the US) compared with placebo in 12-week and 12-month, randomized, double
      blind trials in patients with chronic obstructive pulmonary disease (COPD). The
      bronchodilator efficacy of formoterol 12 microg twice daily was greater than that
      of oral slow-release theophylline (individualized dosages) in a 12-month trial or
      inhaled ipratropium bromide 40 microg four times daily in a 12-week trial.
      Improvement in AUC FEV1 with formoterol, but not theophylline, compared with
      placebo was observed in patients with irreversible or poorly-reversible airflow
      obstruction. Formoterol also significantly improved health-related quality of
      life compared with ipratropium bromide or placebo and significantly reduced
      symptoms compared with placebo. Combination therapy with formoterol 12 microg
      twice daily plus ipratropium bromide 40 microg four times daily was significantly
      more effective than albuterol (salbutamol) 200 microg four times daily plus the
      same dosage of ipratropium bromide in a 3-week, randomized, double-blind, double
      dummy, crossover trial. Inhaled formoterol was well tolerated in clinical trials.
      The incidence of investigator-determined drug-related adverse events with inhaled
      formoterol 12 microg twice daily was similar to that with placebo and inhaled
      ipratropium bromide 40 microg four times daily but lower than that with oral slow
      release theophylline (individualized dosages). Importantly, there were no
      significant differences between formoterol and placebo or comparator drugs in
      cardiovascular adverse events in patients with COPD and corrected QT interval
      values within the normal range. In conclusion, inhaled formoterol improved lung
      function and health-related quality of life and reduced symptoms relative to
      placebo in clinical trials in patients with COPD. The drug had greater
      bronchodilator efficacy than oral slow-release theophylline or inhaled
      ipratropium bromide and showed efficacy in combination with ipratropium bromide.
      The adverse events profile (including cardiovascular adverse events) with
      formoterol was similar to that with placebo. Thus, inhaled formoterol may be
      considered as a first-line option for the management of bronchoconstriction in
      patients with COPD who require regular bronchodilator therapy for the management
      of symptoms.

PMID- 14720053
TI  - Obstructive sleep apnea in children: do intranasal corticosteroids help?
AB  - Obstructive sleep apnea (OSA) is a common condition of childhood, and is
      associated with significant morbidity. Prevalence of the condition peaks during
      early childhood, due in part to adenoidal and tonsillar enlargement within a
      small pharyngeal space. The lymphoid tissues regress after 10 years of age, in
      the context of ongoing bony growth, and there is an associated fall in the
      prevalence of OSA. Obstruction of the nasopharynx by adenoidal enlargement
      promotes pharyngeal airway collapse during sleep, and the presence of large
      tonsils contributes to airway obstruction. Administration of systemic
      corticosteroids leads to a reduction in the size of lymphoid tissues due to anti
      inflammatory and lympholytic effects. However, a short course of systemic
      prednisone has been demonstrated not to have a significant effect on adenoidal
      size or the severity of OSA, and adverse effects preclude the long-term use of
      this therapy. Intranasal corticosteroids are effective in relieving nasal
      obstruction in allergic rhinitis, and allergic sensitization is more prevalent
      among children who snore than among those who do not snore. Intranasal
      corticosteroids have also been demonstrated to reduce adenoidal size, independent
      of the individual's atopic status. There is preliminary evidence of an
      improvement in the severity of OSA in children treated with intranasal
      corticosteroids, but further studies are needed before such therapy can be
      routinely recommended. Prescribing clinicians should take into account the
      potential benefits to the patient, the age of the child, the presence of
      comorbidities such as allergic rhinitis, the agent used, and the dose and
      duration of treatment when considering such therapy.

PMID- 14720054
TI  - Is there a place for inhaled nitric oxide in the therapy of acute pulmonary
      embolism?
AB  - Acute pulmonary embolism (PE) is a serious complication resulting from the
      migration of emboli to the lungs. Although deep venous thrombi are the most
      common source of emboli to the lungs, other important sources include air,
      amniotic fluid, fat and bone marrow. Regardless of the specific source of the
      emboli, very little progress has been made in the pharmacological management of
      this high mortality condition. Because the prognosis is linked to the degree of
      elevation of pulmonary vascular resistance, any therapeutic intervention to
      improve the hemodynamics would probably increase the low survival rate of this
      critical condition. Inhaled nitric oxide (iNO) has been widely tested and used in
      cases of pulmonary hypertension of different causes. In the last few years some
      authors have described beneficial effects of iNO in animal models of acute PE and
      in anecdotal cases of massive PE. The primary cause of death in massive PE that
      is caused by deep venous thrombi, gas or amniotic fluid, is acute right heart
      failure and circulatory shock. Increased pulmonary vascular resistance following
      acute PE is the cumulative result of mechanical obstruction of pulmonary vessels
      and pulmonary arteriolar constriction (attributable to a neurogenic reflex and to
      the release of vasoconstrictors). As such, the vasodilator effects of iNO could
      actively oppose the pulmonary hypertension following PE. This hypothesis is
      consistently supported by experimental studies in different animal models of PE,
      which demonstrated that iNO decreased (by 10 to 20%) the pulmonary artery
      pressure without improving pulmonary gas exchange. Although maximal vasodilatory
      effects are probably achieved by less than 5 parts per million iNO, which is a
      relatively low concentration, no dose-response study has been published so far.
      In addition to the animal studies, a few anecdotal reports in the literature
      suggest that iNO may improve the hemodynamics during acute PE. However, no
      prospective, controlled, randomized clinical trial addressing this issue has been
      conducted to date. Future investigations addressing the effects of iNO combined
      with other drugs such as vasoconstrictors and inhibitors of phosphodiesterase III
      or V, may increase the responsiveness to iNO in acute PE.

PMID- 14720055
TI  - Peptide receptor imaging: advances in the diagnosis of pulmonary diseases.
AB  - Radiolabeled cell-surface peptide receptor-binding molecules are emerging as an
      important class of radiopharmaceuticals. Their binding to specific cell membrane
      receptors allows for noninvasive assessment of regional receptor proteomics in
      vivo. Information thus obtained can be used for diagnostic purposes and for
      predicting and monitoring response to treatment. This paradigm also applies to
      pulmonary diseases. In this review, available radiopharmaceuticals of great
      potential or already in clinical use for imaging of lung cancer, lung
      inflammation and infection and pulmonary embolism are discussed. In lung cancer,
      somatostatin receptor imaging by means of technetium-99m (99mTc)-octreotide
      scintigraphy has proven useful for characterizing malignancy in solitary
      pulmonary nodules. Additionally, several radiopharmaceuticals targeting tyrosine
      kinase, e.g. 99mTc labeled epidermal growth factor and indium-111 (111In)
      diethylene triamine penta-acetic acid-trastuzumab, or G-protein coupled
      receptors, e.g. 99mTc-bombesin, iodine-123-vasoactive intestinal peptide and
      111In-tetraazacyclododecane tetra-acetic acid (DOTA)-cholecystokinine-B, are
      being explored for their diagnostic as well as treatment monitoring potential.
      With the purpose of better evaluating the source of pulmonary embolism, as well
      as to differentiate acute from chronic deep venous thrombosis, several
      radiolabeled peptides targeting the glycoprotein IIb/IIIa fibrinogen receptor
      found on activated platelets have been developed. Out of these, 99mTc-P280 is now
      approved by the US Food and Drug Administration for scintigraphic imaging of
      suspected acute venous thrombosis in the lower extremities of patients. In the
      field of lung inflammation and infection, non-specific 111In and 99mTc-human
      polyclonal immunoglobulins have been successfully used to identify the presence
      and extent of Pneumocystis carinii, cytomegalovirus, Mycobaterium avium and
      fungal infections in patients with HIV infection. The clinical role of other
      radiopharmaceuticals such as 99mTc-J001X, a nonpyrogenic acylated polygalactoside
      isolated from Klebsiella pneumoniae and binding with high affinity to CD11b and
      CD14 lipopolysaccharide receptors expressed on monocytes/macrophages, and 111In
      octreotide, binding to up-regulated somatostatin receptors on activated
      lymphocytes needs to be further defined.

PMID- 14720056
TI  - Biology and therapeutic potential of the interleukin-4/interleukin-13 signaling
      pathway in asthma.
AB  - The future management of patients with allergic asthma is poised to change in the
      coming one to two decades. This prediction is based on fundamental new insights
      into the pathogenesis of disease, gained through the study of both humans and
      experimental models of asthma. These studies have revealed that allergic asthma
      is an immune-mediated disease which, despite the redundancy characteristic of all
      immune responses, may be induced through a single dominant signaling cascade
      called the interleukin (IL)-4/IL-13 signaling pathway. In addition to the
      cytokine IL-4, this pathway includes IL-13, the cytokine receptor subunit IL-4
      receptor alpha (IL-4Ralpha), Janus-associated tyrosine kinases and the
      transcription factor, signal transducer and activator of transcription 6. The IL
      4 signaling pathway controls the most important cellular developmental (afferent)
      events that underlie asthma. These include T helper (Th) type 2 cell activation,
      B cell activation and immunoglobulin (Ig) E secretion, mast cell development, and
      effector (efferent) events related exclusively to immune effects on the lung such
      as goblet cell metaplasia and airway hyperresponsiveness. Any of the IL-4
      signaling molecules are potentially amenable to pharmacological intervention, but
      a detailed understanding of the entire pathway is required to appreciate their
      actual potential for drug development. For example, neutralization strategies
      that target only IL-4 are unlikely to succeed because they leave IL-13 free to
      continue the signaling cascade. In contrast, neutralization of IL-4Ralpha may
      represent a more feasible strategy, as it should prevent signaling by both IL-4
      and IL-13. The therapeutic potential of targeting intracytoplasmic tyrosine
      kinases has already been achieved with the use of small molecules, suggesting
      that this approach may be realistically adopted for the treatment of asthma.
      However, well designed asthma clinical trials are warranted to determine with
      certainty, the efficacy of therapies based on IL-4/IL-13 blockade.

PMID- 14720057
TI  - Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal
      congestion.
AB  - Patients with allergic rhinitis frequently present with symptoms of nasal
      congestion, runny nose, sneezing, daytime somnolence and fatigue associated with
      decreased cognitive performance and impaired quality of life. Recent research has
      suggested that daytime somnolence in allergic rhinitis can be attributed to
      chronic inflammation of the nasal mucosa leading to nasal congestion and
      obstructed nasal passageways resulting in disturbed sleep. Treating daytime
      somnolence due to allergic rhinitis requires a reduction in obstruction caused by
      nasal congestion. Currently available therapy for allergic rhinitis includes
      topical corticosteroids, sedating and nonsedating antihistamines, topical
      cromolyn sodium (sodium cromoglycate), decongestants, immunotherapy and topical
      ipratropium bromide. The effectiveness of antihistamines in patients with
      allergic rhinitis has long been established. However, results of placebo
      controlled trials investigating the effects of azelastine on sleep and daytime
      somnolence have produced conflicting results. Sleep improved with azelastine
      therapy, but there was a lack of evidence that azelastine significantly affected
      daytime sleepiness, sleep severity and nasal congestion. Sedating antihistamines
      exacerbate daytime somnolence and should be avoided in patients with allergic
      rhinitis. In a separate study, desloratadine failed to benefit sleep, but did not
      worsen daytime somnolence. Topical nasal cromolyn sodium is inconvenient to use
      and is unlikely to have a major effect on nasal congestion. Decongestants do
      decrease nasal congestion but the effect this has on sleep has not been
      adequately studied. Recent research has shown that topical corticosteroids are an
      effective treatment for alleviating nasal congestion secondary to allergic
      rhinitis. However, few studies have assessed the effect of topical
      corticosteroids on daytime fatigue and sleep. In 20 patients with allergic
      rhinitis and symptoms of daytime sleepiness, flunisolide significantly improved
      sleep quality and congestion but daytime sleepiness was not significantly
      improved. A similar study with fluticasone propionate showed improvement in nasal
      congestion and sleep but there was no significant change in objective sleep
      measurements recorded on polysomnography. Further research involving objective
      measures of sleep quality is necessary to determine the efficacy of medications
      in the treatment of allergic rhinitis associated with fatigue and daytime
      somnolence.

PMID- 14720058
TI  - Intrapulmonary pharmacokinetics of antibacterial agents: implications for
      therapeutics.
AB  - The idea of studying the pharmacokinetics and pharmacodynamics of antibacterials
      in order to predict their efficacy has long been of interest. Traditionally,
      serum drug concentrations have been evaluated against the minimum inhibitory
      concentration (MIC) of a given pathogen; however, infection site-specific data
      continue to gain interest from clinicians. Despite methodological limitations,
      progress in techniques has improved the clinical significance of data generated.
      Rather than using tissue homogenates which fail to differentiate between
      interstitial and intracellular concentrations, newer collection techniques focus
      on sampling of matrices that allow for this differentiation. These collection
      techniques now allow one to accurately describe beta-lactam and aminoglycoside
      interstitial penetrations, as well as, the interstitial and phagocytic
      concentrations of macrolides and fluoroquinolones. By using these specific data
      and the MICs of infecting pathogens, it is hoped that conclusions can be drawn by
      a clinician as to the appropriateness of the choice of an antibacterial.

PMID- 14720059
TI  - Idiopathic pulmonary fibrosis: current and future treatment options.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology
      with an unfavorable outcome from progressively deteriorating respiratory
      function, leading ultimately to death from respiratory failure. It is
      characterized by sequential acute lung injury resulting in progressive fixed
      tissue fibrosis, architectural distortion and loss of function. An excess of
      profibrotic cytokines and/or a deficiency in antifibrotic cytokines have been
      implicated in the pathological process as has excessive oxidation. IPF is
      distinguished from other forms of diffuse pulmonary fibrosis by the presence of
      the specific histological pattern of usual interstitial pneumonitis. Oral
      corticosteroids are the usual treatment, but objective response rates are poor
      and good quality studies do not exist. Other therapies either alone or in
      combination with corticosteroids are widely used, including azathioprine,
      colchicine, cyclophosphamide and penicillamine. There is a paucity of good
      quality information regarding the effectiveness of most noncorticosteroid
      immunosuppressive agents. Older studies of lesser methodological quality have
      shown benefits from these drugs, generally when added to corticosteroids. Many
      were retrospective reviews or uncontrolled, nonrandomized, open-label,
      prospective studies and often included other histological patterns of disease
      which are now thought to respond better to immunosuppressive agents. The results
      of intervention with colchicine and azathioprine have been disappointing when
      assessed by good quality trials using modern diagnostic criteria. Modern high
      quality studies are lacking for several agents, notably cyclophosphamide and
      penicillamine. The older agents may yet prove to be effective but further good
      quality trials will be necessary to assess these agents adequately. Other new
      anti-inflammatory, antioxidant, antifibrotic or anticytokine compounds are
      largely untried or unreported. One trial using interferon-gamma-1b showed a
      significant improvement in pulmonary function but there are concerns regarding
      the generalizability of this study. Pirfenidone, cyclosporine and acetylcysteine
      may also prove to be of benefit but current studies are of insufficient quality
      to allow for any conclusions to be drawn. Currently there is no good evidence to
      support the routine use of oral corticosteroids, azathioprine, cyclophosphamide,
      penicillamine, colchicine, cyclosporine or any other immunosuppressive,
      antifibrotic or immunomodulatory agent in the management of IPF. Interferon,
      pirfenidone and other new agents may be of benefit but further studies are
      required. Any recommendations for treatment must therefore be made on an
      individual and empiric basis. As some other forms of pulmonary fibrosis may
      respond better to immunosuppressive agents, it remains important to make an
      accurate diagnosis, by open lung biopsy if necessary.

PMID- 14720060
TI  - Spotlight on montelukast in asthma in children 2 to 14 years of age.
AB  - Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a
      preventive treatment for persistent asthma in patients > or =2 years of age. In
      children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a
      significant increase in FEV1 (forced expiratory volume in 1 second, primary
      clinical outcome) during an 8-week randomized, double-blind trial. Moreover,
      significant improvements were observed for a range of secondary endpoints
      assessing symptoms, exacerbation rates, beta-agonist usage and quality of life.
      Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200
      microg twice daily) resulted in a trend towards an increase in FEV1 (p=0.06,
      primary endpoint) and a statistically significant reduction in both as-needed
      beta2-agonist usage and the percentage of days with asthma exacerbations compared
      with budesonide plus placebo. No significant differences were observed in asthma
      related quality of life between the two groups. During clinical trials both
      improvements in lung function and reductions in as-needed beta2-agonist usage
      were generally observed within 1 day after initiation of therapy in children 2 to
      14 years of age with persistent asthma. Data from a randomized, nonblind trial in
      6- to 11-year-old children and a 6-month extension to this trial suggest that
      both compliance to therapy and patient satisfaction are greater for montelukast
      than for either inhaled cromolyn sodium (sodium cromoglycate) or inhaled
      beclomethasone. In addition, patients and parents preferred oral montelukast over
      cromolyn sodium. In 2- to 5-year-old children with persistent asthma, montelukast
      (4 mg/day) treatment resulted in significant improvements in a range of outcomes,
      such as as-needed beta2-agonist usage, symptom scores and percentage of days with
      asthma symptoms, as assessed during a randomized, double-blind trial primarily
      designed to assess tolerability. Data from small randomized, double-blind trials
      suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14
      year-old children. Montelukast is generally well tolerated. The frequency of
      adverse events in montelukast-treated children of all ages was comparable to that
      in patients receiving placebo. CONCLUSION: Oral montelukast has shown efficacy as
      a preventive treatment for asthma during clinical trials in children aged 2 to 14
      years. The drug offers benefits over more standard therapies such as inhaled
      cromolyn sodium and nedocromil in terms of compliance and convenience. In
      addition, the drug offers significant benefits when added to inhaled
      corticosteroids (according to secondary endpoints). Montelukast offers an
      effective, well tolerated and convenient treatment option for children with
      asthma.

PMID- 14720062
TI  - Neuraminidase inhibitors in patients with underlying airways disease.
AB  - Influenza virus infection accounts for significant morbidity, mortality, and
      healthcare expenditures among persons worldwide. Approximately 20,000 to 40,000
      people in the US die each year as a result of influenza. Individuals most
      susceptible to adverse outcomes include the elderly and those with asthma,
      chronic obstructive pulmonary disease (COPD), heart disease, renal failure,
      malignancy, or immunosuppression. Prior to the AIDS epidemic, underlying
      respiratory disease was the greatest risk factor for influenza-related
      hospitalization ranking third to heart disease and malignancy for risk of
      mortality. Although the influenza vaccine can help prevent pneumonia and
      hospitalization, it is limited by less than ideal immunization rates and the
      possibility of viral antigenic shifts that render the vaccine ineffective.
      Pharmacologic interventions play an important role in the management of influenza
      virus infection by shortening the duration of symptoms. The advent of the
      neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has significantly
      affected the treatment of influenza. Unlike NAIs, the older therapeutic options
      amantadine and rimantadine may cause significant central nervous system adverse
      effects. In addition, amantadine and rimantadine are not active against influenza
      B viruses, whereas NAIs are active against both influenza A and B. Post-marketing
      surveillance of the NAIs has revealed that bronchospasm may occur in patients
      with underlying respiratory disease treated with the NAI zanamivir. Recent data
      suggest zanamivir is effective in patients with underlying respiratory disease,
      but the data are insufficient to elucidate the true risk of bronchospasm. Based
      on post-marketing reports, zanamivir should be used with caution in patients with
      asthma or COPD. Although oseltamivir has not been associated with any significant
      respiratory adverse effects, no data exist on the safety and efficacy of this NAI
      in patients with underlying respiratory disease.

PMID- 14720063
TI  - Sublingual tacrolimus for immunosuppression in lung transplantation: a
      potentially important therapeutic option in cystic fibrosis.
AB  - Lung transplantation has emerged as an option to prolong and increase the quality
      of life in patients with end-stage pulmonary lung disease. In lung transplant
      recipients, because of the high potential for acute and chronic allograft
      rejection, optimal selection, dosage and delivery of immunosuppressive
      medications is critical. Cystic fibrosis (CF), a multi-organ system disease that
      often includes pulmonary and gastrointestinal manifestations, represents the
      leading indication for bilateral lung transplantation. The gastrointestinal
      manifestations of CF, however, confound post-transplant management by causing
      significant variation in the rate and extent of absorption of orally administered
      immunosuppressive medications. Tacrolimus, a new calcineurin inhibitor, is
      increasingly employed as the primary immunosuppressive agent in lung transplant
      recipients. Unfortunately, tacrolimus itself exhibits variable bioavailability,
      particularly in CF transplant recipients. A novel approach to the absorption
      dilemma is administration of tacrolimus via the sublingual (SL) route. Little
      published information exists concerning the use of SL immunosuppression in
      transplant recipients. However, emerging evidence suggests that SL tacrolimus
      provides is an effective means of drug delivery particularly for CF lung
      transplant recipients. Preliminary results from a pilot study, demonstrate that
      SL delivery of tacrolimus achieves therapeutic serum levels, in lung transplant
      recipients with CF, over the first few postoperative months. In addition, the
      early postoperative use of SL tacrolimus has been associated with acceptable
      rates of transplant rejection and normal renal function in a cohort of 22 lung
      transplant recipients that included CF and non-CF transplant recipients.
      Potential pharmacokinetic advantages of the SL route of delivery include good
      permeability, rapid absorption, acceptable bioavailability and easy
      accessibility. From an economic standpoint, considerable cost savings could be
      achieved by using the SL rather than the intravenous route of drug delivery for
      tacrolimus. Comparative, prospective randomized trials are necessary to evaluate
      the long-term safety and efficacy of SL tacrolimus in lung transplant patients.
      Until such data are available, the use of SL tacrolimus should be considered in
      situations where alternative routes of delivery are unavailable or as part of
      ongoing research studies. Ultimately, SL tacrolimus may prove efficacious for
      short-term use in the early postoperative lung transplant recipients,
      particularly in patients with malabsorption problems such as CF transplant
      recipients.

PMID- 14720064
TI  - Targeting adenosine receptors: novel therapeutic targets in asthma and chronic
      obstructive pulmonary disease.
AB  - Adenosine, an endogenous signaling nucleoside that modulates many physiological
      processes has been implicated in playing an ever increasingly important role in
      the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). All
      cells contain adenosine and adenine nucleotides and the cellular production of
      adenosine is greatly enhanced under conditions of local hypoxia as may occur in
      inflammatory conditions such as asthma and COPD. In 1983, it was first reported
      that inhaled adenosine causes dose-related bronchoconstriction in patients with
      both allergic and non-allergic asthma but not in healthy volunteers. This
      hyperresponsiveness was also reported in patients with COPD, with those patients
      who smoked exhibiting a significantly greater response. This bronchoconstrictor
      effect of adenosine is orchestrated through the stimulation of specific cell
      membrane receptors and involves an important inflammatory cell, the mast cell.
      There is substantial evidence which suggests that mast cell activation is central
      to this unique response to adenosine. Mast cell mediator release makes a
      significant contribution towards airflow obstruction and the consequent symptoms
      in patients with asthma. Over the last two decades, researchers have investigated
      the effect of mast cell inhibitors as well as mast cell mediator receptor
      antagonists and their role in attenuating the bronchoconstrictor response to
      inhaled adenosine 5'-monophosphate (AMP). Promising results have been shown using
      mast cell stabilizers, histamine H1 receptor antagonists, selective cysteinyl
      leukotriene-1 receptor antagonists and inhibitors of 5-lipoxygenase and cyclo
      oxygenase. Through these findings, the mast cell has been recognized as being a
      critical inflammatory cell in the adenosine-induced response in patients with
      asthma and COPD. To date, four subtypes (A1, A2A, A2B, A3) of adenosine receptors
      have been cloned each with a unique pattern of tissue distribution and signal
      transduction. Activation of these receptors has pro- and anti-inflammatory
      consequences making the development of agonists and/or antagonists at these
      receptor sites a novel approach in the treatment of patients with asthma and
      COPD. This review highlights the importance of adenosine in the pathophysiology
      of asthma and COPD, the critical role of the mast cell and the potential to
      target the adenosine receptor subtype in patients with asthma and COPD. The
      complete characterization of these adenosine receptor subtypes in terms of their
      distribution in humans and the development of selective agonists and antagonists,
      holds the key to our complete understanding of the role of this important
      mediator in asthma and COPD.

PMID- 14720065
TI  - Nontuberculous mycobacterial pulmonary infection in patients with cystic
      fibrosis: diagnosis and treatment.
AB  - The prevalence of nontuberculous mycobacteria (NTM) recovered from patients with
      cystic fibrosis (CF) appears to be increasing, probably related to improved
      surveillance and microbiological procedures and an increase in the life
      expectancy of patients with CF. The distinction between active lung infection and
      colonization is often difficult to assess in patients with CF because of the
      marked overlap in the clinical and radiological presentation of CF lung disease
      and lung disease caused by NTM infection. The possibility of active NTM lung
      infection should be considered in those patients with compatible radiographic
      changes and/or progressive deterioration in lung function who do not improve with
      specific antibiotic therapy and who have repeatedly positive sputum cultures and
      smears for NTM. Patients with repeatedly positive results of acid-fast smears are
      more likely to be infected than colonized. Pseudomonas overgrowth may confuse the
      results of sputum and bronchoalveolar lavage fluid cultures. Decontamination of
      respiratory samples from patients with CF with 5% oxalic acid results in improved
      bacteriological recovery of NTM. Skin tests are of limited value as a screening
      tool for NTM. Since the course of NTM lung infection is often slow, careful
      follow-up with repeated sputum cultures, chest radiographs and computed
      tomography (CT) scans may be needed. Treatment of NTM lung disease in patients
      with CF presents great difficulties because of abnormal gastrointestinal drug
      absorption and pharmacokinetics in this patient population. Treatment varies
      according to the mycobacterial species isolated. Long-term multidrug regimens
      including rifampin (rifampicin) and ethambutol are usually required. Monitoring
      serum drug levels is a useful indicator of correct dosage in order to prevent
      adverse effects due to potential drug interactions and altered pharmacokinetics
      in patients with CF.

PMID- 14720066
TI  - Diffuse panbronchiolitis: role of macrolides in therapy.
AB  - Diffuse panbronchiolitis (DPB) is characterized by chronic sinobronchial
      infection and diffuse bilateral micronodular pulmonary lesions consisting of
      inflammatory cells. Studies on disease etiology point to a genetic predisposition
      unique to Asians. Early therapy for DPB was largely symptomatic. The advent of
      macrolide antibiotics, including erythromycin, roxithromycin and clarithromycin,
      has strikingly changed disease prognosis. Low-dose, long-term macrolide therapy
      for DPB originated from detailed observations of response to therapy in a single
      patient. The bactericidal activity of macrolides, particularly erythromycin, is
      not a significant factor for their clinical efficacy in DPB. Firstly,
      irrespective of bacterial clearance, clinical improvement is observed in patients
      treated with erythromycin. Secondly, even in cases with bacterial superinfection
      with Pseudomonas aeruginosa resistant to macrolides, treatment has proved
      effective. Thirdly, the recommended dosage of macrolides produces peak levels in
      tissue that are below the minimum inhibitory concentrations for major pathogenic
      bacteria that colonize the airway. In the last two decades, the possible
      mechanism underlying the effectiveness of macrolide therapy has been extensively
      studied. The proposed mechanism of action includes inhibition of excessive mucus
      and water secretion from the airway epithelium, inhibition of neutrophil
      accumulation in the large airway, inhibition of lymphocyte and macrophage
      accumulation around the small airway, and modulation of bacterial virulence. The
      great success of macrolide therapy in diffuse panbronchiolitis may extend its
      application to the treatment of other chronic inflammatory disorders. If the anti
      inflammatory activity of macrolides is independent of their bactericidal effect,
      new anti-inflammatory macrolides without antimicrobial activity should be
      developed to minimize emergence of macrolide-resistant micro-organisms.

PMID- 14720067
TI  - The association of gastroesophageal reflux disease with asthma and chronic cough
      in the adult.
AB  - Gastroesophageal reflux disease (GERD) is a common condition which is
      particularly prevalent in patients with asthma and chronic cough. Physiologic
      changes caused by asthma and chronic cough promote acid reflux. GERD is also
      considered by many investigators as a factor contributing to airway inflammation.
      An etiological relationship between GERD and asthma/chronic cough and vice versa
      has been supported by a large number of experimental and clinical findings and
      refuted by others. Although further controlled studies are needed to clarify this
      relationship, GERD and asthma/chronic cough appear to be linked to each other.
      The association of GERD with asthma and chronic cough involves nerve reflexes,
      cytokines, inflammatory and neuroendocrine cells and, in some patients, tracheal
      aspiration of refluxing gastric fluids. GERD may present with typical symptoms
      but can also be asymptomatic. Sensitive methods for diagnosing GERD are
      available, which include esophageal pH monitoring, acid provocative tests,
      modified barium swallow and endoscopy. Consideration of the association of GERD
      with asthma and chronic cough is of practical value in the management of chronic
      cough or asthma resistant to treatment. Treatment of GERD in patients with asthma
      has been consistently shown to improve respiratory symptoms but not necessarily
      pulmonary function tests. Surgical treatment can be a useful and cost-effective
      approach in selected patients with asthma and GERD.

PMID- 14720068
TI  - Spotlight on zanamivir in influenza.
AB  - Zanamivir is a potent competitive inhibitor of the neuraminidase glycoprotein,
      which is essential in the infective cycle of influenza A and B viruses. Zanamivir
      (10 mg by inhalation via the Diskhaler twice daily, or 10 mg inhaled plus 6.4 mg
      intranasally 2 or 4 times daily, for 5 days) reduced the median time to
      alleviation of major influenza symptoms by up to 2.5 days compared with placebo.
      Significant reductions of 1 to 2.5 days versus placebo were observed with inhaled
      zanamivir in phase III trials involving otherwise healthy adults, high-risk
      patients or children aged 5 to 12 years. Accelerated return to normal activities,
      and reduced interference with sleep, consumption of relief medication and
      incidence of complications leading to antibacterial use were also observed with
      zanamivir. When used for prophylaxis, inhaled zanamivir 10 to 20 mg/day for 10
      days to 4 weeks (plus 6.4 mg/day intranasally in one trial) prevented influenza A
      in 67% of recipients in a university community, significantly reduced the number
      of families with new cases of influenza compared with placebo or prevented new
      cases of influenza in long-term care facilities. The tolerability of inhaled or
      intranasal zanamivir was similar to that of placebo in otherwise healthy adults,
      high-risk and elderly patients, and children. Recommended dosages of zanamivir
      did not adversely affect pulmonary function in patients with respiratory
      disorders in a well-controlled trial, although there have been rare reports of
      bronchospasm and/or a decline in respiratory function. In conclusion, zanamivir
      (used within 48 hours of symptom development) reduces the duration of symptomatic
      illness, causes accelerated return to normal activities or reduces complications
      requiring antibacterial use in adults, high-risk individuals and children with
      influenza. Vaccination remains the intervention of choice for prophylaxis in
      selected populations. However, the efficacy, good tolerability profile and lack
      of resistance with zanamivir make it a useful option, particularly in those not
      covered or inadequately protected by vaccination, who are able to use the
      inhalation device. The use of zanamivir in patients with respiratory disorders
      remains unclear because of concerns regarding its potential for bronchospasm.
      Prospective cost-effectiveness analyses and investigations of efficacy in
      preventing serious complications of influenza, particularly in high-risk
      patients, are required. Zanamivir shows potential for prophylaxis in persons for
      whom vaccination is contraindicated or ineffective, in elderly or high-risk
      patients in long-term care facilities and in households.

PMID- 14720070
TI  - Influenza vaccination: is it appropriate in chronic fatigue syndrome?
AB  - Chronic fatigue syndrome (CFS) is a recognized clinical illness of unknown cause
      and pathophysiologic mechanisms. Immunizing patients against influenza would seem
      to be a prudent strategy since infection has been associated with symptom
      exacerbation. However, patients with CFS have demonstrated variable abnormalities
      in the immune system, the clinical significance of which is unclear. Anecdotal
      information has suggested that, due to the etiologic uncertainty surrounding CFS,
      many patients reject immunization, fearful of untoward effects. This article
      attempts to clarify the situation by reviewing immunologic findings in CFS and
      influenza vaccines in current use. Results from a recent survey of perceptions of
      patients with CFS regarding immunization revealed that 31% felt immunization was
      neither safe nor beneficial. This opinion was universal in those patients who had
      never received influenza vaccine. Among patients who had received vaccine and
      experienced an adverse effect, 26% felt the vaccine was safe and 28% felt it was
      beneficial. Among those who had received vaccine without an adverse effect, 45%
      believed the vaccine was safe, and 55% felt it was effective. CFS patients as a
      group expressed concern that influenza vaccine would alter an already
      dysfunctional immune system, or worsen CFS symptoms. Significantly more patients
      with CFS who had never received influenza vaccine voiced this opinion than did
      patients who had received immunization for influenza in the past. Contrary to the
      opinions expressed by the sample, clinical trials in CFS have yet to find that
      any type of immunization has produced a deleterious effect on symptoms or
      functioning. Moreover, patients with CFS in a randomized, placebo-controlled,
      double-blind trial of influenza immunization produced an antibody titer in the
      protective range to inactivated trivalent influenza vaccine, although the
      geometric mean titer was slightly blunted compared with healthy vaccinees.
      Although patients with CFS in placebo and active groups reported four times the
      number of post-injection adverse effects of healthy vaccinees, data re-analysis
      revealed that this finding was related to the overlap of common, post-influenza
      immunization symptoms and CFS constitutional symptoms. CFS is a poorly understood
      illness and some patients may believe in causal theories that lead to the
      rejection of disease prevention strategies such as immunization. However,
      influenza immunization appears to provide protective antibody levels without
      worsening CFS symptoms or causing excessive adverse effects. Efforts to motivate
      patients with CFS to obtain annual influenza immunization should take into
      account illness perceptions and concentrate on education based on placebo
      controlled trials.

PMID- 14720071
TI  - Thromboxane A2 inhibition: therapeutic potential in bronchial asthma.
AB  - Bronchial asthma is a disease defined by reversible airway obstruction, bronchial
      hyperresponsiveness and inflammation. In addition to histamine and acetylcholine,
      recent studies have emphasized the role of arachidonic acid metabolites
      (leukotrienes, prostaglandins and thromboxane A(2)) in the pathogenesis of
      asthma. Among these mediators, thromboxane A(2) (TXA(2)) has attracted attention
      as an important mediator in the pathophysiology of asthma because of its potent
      bronchoconstrictive activity. Thromboxane A(2) is believed to be involved not
      only in late asthmatic responses but also in bronchial hyperresponsiveness, a
      typical feature of asthma. Strategies for inhibition of TXA(2) include TXA(2)
      receptor antagonism and thromboxane synthase inhibition. Results of double-blind,
      placebo-controlled clinical trials have proven the efficacies of the thromboxane
      receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in
      the treatment of patients with asthma. Seratrodast and ozagrel are available in
      Japan for the treatment of asthma. Ramatroban, another thromboxane receptor
      antagonist, is currently under phase III clinical evaluation in Europe and Japan
      for the treatment of asthma. The pharmacological profiles of the thromboxane
      modulators may be improved by combination with leukotriene D(4) receptor
      antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel
      orally active dual antagonist for leukotriene D(4) and thromboxane A(2
      )receptors, may have potent therapeutic effects in the treatment of bronchial
      asthma. Large scale clinical trials are necessary to further define the role of
      thromboxane modulators in the treatment of patients with asthma.

PMID- 14720072
TI  - The role of interleukin-8 and its receptors in inflammatory lung disease:
      implications for therapy.
AB  - Neutrophils have been implicated in the pathogenesis of many inflammatory lung
      diseases, including the acute respiratory distress syndrome, chronic obstructive
      pulmonary disease and asthma. The CXC chemokine interleukin (IL)-8, is a potent
      neutrophil recruiting and activating factor and the detection of IL-8 in clinical
      samples from patients with these diseases has led clinicians to believe that
      antagonism of IL-8 may be a practicable therapeutic strategy for disease
      management. Work over the last decade has concentrated on both the molecular
      mechanisms by which IL-8 is produced in the inflammatory setting and also on the
      manner in which IL-8 activates the neutrophil. Expression of the IL-8 gene
      appears to be controlled by several components of the inflammatory milieu. Whilst
      lipopolysaccharide, IL-1beta and tumor necrosis factor-alpha are capable of
      augmenting IL-8 production, IL-10 is a potent inhibitor of IL-8 synthesis and
      appears to play an auto-regulatory role. Regulation of the IL-8 gene is under the
      control of nuclear factor kappaB which appears to be a primary target for
      corticosteroid-mediated repression of IL-8 production. IL-8 exerts is effects on
      neutrophils by binding with high affinity to two receptors on its cell surface,
      the chemokine receptors CXCR1 and CXCR2. These closely related receptors belong
      to the superfamily of G-protein coupled receptors, proteins that historically
      have proved amenable to antagonism by small molecules. The recent descriptions in
      the literature of highly potent small molecule antagonists of CXCR2 and their
      success in blocking in vivo trafficking of neutrophils suggest that antagonism of
      IL-8 at the receptor level is a viable therapeutic strategy. Clinical trials of
      such compounds will ultimately provide crucial information currently lacking and
      will define whether or not IL-8 blockade provides future therapy in pulmonary
      disease.

PMID- 14720073
TI  - Second-generation antihistamines in asthma therapy: is there a protective effect?
AB  - Second-generation histamine H(1) receptor antagonists are recognized as being
      highly effective treatments for allergic-based disease and are among the most
      frequently prescribed drugs in the world. The newer antihistamines represent a
      heterogeneous group of compounds with markedly different chemical structures, a
      spectrum of antihistaminic properties, adverse effects, half-life, tissue
      distribution, metabolism and varying degrees of anti-inflammatory effects.
      Histamine is an important mast cell- and basophil-derived mediator that has been
      implicated in the pathogenesis of asthma, resulting in smooth muscle contraction,
      mucus hypersecretion, and increased vascular permeability leading to mucosal
      edema. Antihistamines should never be used as monotherapy for asthma but there is
      evidence that these drugs give a measure of protection in histamine-induced
      bronchoconstriction. Furthermore, several studies have demonstrated that the use
      of second-generation antihistamines, as adjunct therapy, may benefit those
      patients whose allergic asthma co-exists with allergic rhinitis. Indeed, many
      patients present with both allergic rhinitis and asthma. The link between the
      upper and lower respiratory airways is now well established and there is
      increasing evidence that allergic rhinitis is a risk factor for the development
      of asthma. More recently, a number of novel antihistamines have been developed
      which are either metabolites of active drugs or enantiomers and there is emerging
      evidence that at least one of these drugs, desloratadine, may give significant
      symptomatic benefit in some types of asthma. It is of interest to note that
      cetirizine provides a primary pharmacological intervention strategy to prevent
      the development of asthma in specifically-sensitized high risk groups of infants.
      Moreover, the documented anti-inflammatory activities of antihistamines may
      provide a novel mechanism of action for the therapeutic control of virus-induced
      asthma exacerbations by inhibiting the expression of intercellular adhesion
      molecule-1 (ICAM-1) by airway epithelial cells. Finally, several well-conducted
      studies suggest that combination therapy with antihistamines and antileukotrienes
      may be as effective as corticosteroid use in patients with allergic asthma and
      seasonal allergic rhinitis.

PMID- 14720074
TI  - Delivery systems for pulmonary gene therapy.
AB  - Delivery of therapeutic genes to the lungs is an attractive strategy to correct a
      variety of pulmonary dysfunctions such as cystic fibrosis, alpha-1 antitrypsin
      deficiency, pulmonary hypertension, asthma, and lung cancer. Different delivery
      routes such as intratracheal instillation, aerosol and intravenous injection have
      been utilized with varying degrees of efficiency. Both viral and non-viral
      vectors, with their respective strengths and weaknesses, have achieved
      significant levels of transgene expression in the lungs. However, the application
      of gene therapy for the treatment of pulmonary disease has been handicapped by
      various barriers to the delivery vectors such as serum proteins during
      intravenous delivery, and surfactant proteins and mucus in the airway lumen
      during topical application of therapeutic genes. Immune and cytokine responses
      against the delivery vehicle are also major problems encountered in pulmonary
      gene therapy. Despite these shortcomings much progress has been made to enhance
      the efficiency, as well as lower the toxicity of gene therapy vehicles in the
      treatment of pulmonary disorders such as cystic fibrosis, lung cancer and asthma.

PMID- 14720075
TI  - Asthma refractory to glucocorticoids: the role of newer immunosuppressants.
AB  - Asthma is orchestrated by cytokine products of activated T cells. Glucocorticoids
      are thought to ameliorate asthma at least partly through T cell inhibition.
      Consequently, other T cell immunomodulatory agents have been assessed for asthma
      therapy. Since these agents may have serious unwanted effects, attention has been
      focused on patients with severe asthma refractory to maximal topical, and
      additional systemic glucocorticoid therapy. Although gold salts show a modest but
      significant glucocorticoid-sparing effect in severe asthma, lung function is not
      improved and not all patients respond. The minimum duration of a valid trial of
      therapy is probably 6 months. Unwanted effects include dermatitis, hepatic
      dysfunction, proteinuria and interstitial pneumonitis. Meta-analysis of trials of
      methotrexate in oral glucocorticoid-dependent asthma have confirmed that
      concomitant weekly methotrexate for a minimum of 3 to 6 months enables
      significant (approximately 20%) overall reduction in oral glucocorticoid
      requirements, although only approximately 60% of patients show a significant
      response. There is little effect on lung function. Blood count and liver function
      must be monitored. Opportunistic infection is rare but potentially fatal.
      Cyclosporine, administered for at least 3 months, is effective in only a
      proportion of patients with oral glucocorticoid-dependent asthma, where it may
      improve disease severity and/or enable oral glucocorticoid dosage reductions.
      Regular monitoring of renal function, blood pressure and blood concentrations of
      cyclosporine is required. The evidence that intravenous immunoglobulin (Ig) is of
      any benefit in patients with glucocorticoid-dependent asthma is at present
      equivocal. The therapy is expensive and associated with a high incidence of
      unwanted effects (fever, aseptic meningitis, urticaria). The macrolides
      tacrolimus (FK506) and sirolimus (rapamycin) have end effects similar to those of
      cyclosporine. Brequinar sodium, mycophenolate mofetil and leflunomide are
      inhibitors of de novo synthesis of pyrimidines and purines, to which T cells are
      particularly sensitive. Such drugs may in theory be beneficial for therapy of
      patients with oral glucocorticoid-dependent asthma. Humanized anti-CD4, anti-IgE
      and anti-interleukin (IL)-5 monoclonal antibodies, and other cytokine inhibitors
      such as soluble IL-4 receptor have entered early trials. The worth of current
      immunomodulatory drugs is limited since: (i) not all patients respond, and
      response cannot be predicted a priori; (ii) the high incidence of unwanted
      effects makes it difficult to assess overall benefit/risk ratios; (iii) there is
      increased risk of opportunistic infection and (theoretically) neoplasia; (iv)
      there are many relative and absolute contraindications to therapy; and (v) there
      is lack of knowledge about the long-term effects, beneficial or otherwise, of
      therapy.

PMID- 14720076
TI  - Long-acting beta2-agonists: comparative pharmacology and clinical outcomes.
AB  - Salmeterol and formoterol are both long-acting beta(2)-adrenoceptor agonists
      (beta(2)-agonists). They both provide excellent bronchodilating and
      bronchoprotective effects in patients with asthma but their are some differences
      between these two long-acting beta(2)-agonists in vitro and in vivo. Formoterol
      has a greater potency and intrinsic activity than salmeterol, which can become
      especially apparent at higher doses than that clinically recommended, and in
      contracted bronchi. Long-term use of long-acting beta(2)-agonists can induce
      tolerance, which can be partially reversed with corticosteroids. Long-acting
      beta(2)-agonists have some anti-inflammatory effects in vitro, but data in vivo
      are less convincing. Compared with doubling the dose of inhaled corticosteroids,
      the addition of inhaled long-acting beta(2)-agonists to inhaled corticosteroids
      improves symptom control in patients with asthma and reduces both the
      exacerbation rate of asthma and hospital admission rate. No enhanced airway
      responsiveness or loss of perception of dyspnea has been observed with the use of
      inhaled long-acting beta(2)-agonists. Monotherapy with long-acting beta(2)
      agonists is not recommended.

PMID- 14720078
TI  - Assessing the value of antipsychotics for treating schizophrenia: the importance
      of evaluating and interpreting the clinical significance of individual service
      costs.
AB  - Schizophrenia is a serious and complex disorder, with treatment requiring a large
      number and wide range of health and social service resources. This paper
      addresses one challenge for assessing the direct costs of antipsychotic
      treatments - that of interpreting both cost and effectiveness implications of
      specific components of service use. Information collected on direct component
      costs has frequently been analysed and reported only in total. Results of several
      published studies provide evidence that the total direct medical costs associated
      with atypical antipsychotics appear to be at least equivalent to, and in some
      cases lower than, those associated with conventional agents. An important
      implication of this cost-equivalency finding is that treatment involving higher
      medication costs have led to offsets in certain medical service costs. Results
      from several studies demonstrate a shift of cost components, primarily from more
      expensive inpatient to less expensive outpatient care. Although the common
      inpatient versus outpatient dichotomy is useful, the complexities of
      schizophrenia and the heterogeneity of outpatient service provision are likely to
      warrant greater specificity. Published schizophrenia treatment guidelines can
      assist researchers to more fully understand and meaningfully interpret the
      possible relationship of antipsychotic effectiveness to the use of particular
      outpatient services. Because the disease requires comprehensive and continuous
      care, outpatient treatment costs may be better conceptualised as baseline or
      expectable costs necessary in the maintenance phase of treatment. Lack of
      expectable costs may represent poor patient outcomes and increased intangible
      costs. In contrast, reductions in acute outpatient service costs may provide
      important markers of treatment effectiveness. A small number of studies have
      examined the use of crisis services, but additional work is needed to
      differentiate treatments vis-a-vis the need for intensive (acute) interventions.
      The assessment and clinical interpretation of individual cost components may
      offer an important opportunity to build upon initial results focusing on total
      costs and tailor analyses to the complexities of the disorder and the treatment
      process. Research able to incorporate clinical acumen into cost analyses will
      enhance the ability of healthcare policy makers to make informed decisions
      regarding the value of different antipsychotic medications for the treatment of
      schizophrenia.

PMID- 14720080
TI  - Why did drug spending increase during the 1990s? A decomposition based on Swedish
      data.
AB  - OBJECTIVE: To decompose drug spending in Sweden between the years 1990 and 2000.
      This paper updates a previous study, which looked at the period 1990-1995, by
      providing an additional 5 years of data (1995-2000) and extending the previous
      analysis in a number of ways. METHODS: The paper builds on the earlier work that
      showed that changes in drug spending could be decomposed into three components:
      price, quantity and a residual. The size of the residual is a measure of the
      impact of changes in drug treatment patterns on drug spending. The data set used
      in this paper was collected from Apoteket AB (The National Corporation of Swedish
      Pharmacies) and was based on comprehensive information (inpatients as well as
      outpatients) on drug deliveries from wholesalers to pharmacies. Data were
      obtained for aggregate drug spending (from 1990-2000) and for spending according
      to anatomical therapeutic chemical (ATC) classification system group. RESULTS:
      Real drug spending increased by 119% during the study period. The residual rose
      by 67% indicating the switch from cheaper to more innovative and expensive drug
      therapies was a major cost driver. Real drug spending would have increased by
      about 31% if there had been no changes in treatment patterns. The second driver
      of drug spending was the quantity of drugs consumed, which increased by 41%. The
      main reason for the larger quantity sold appears to be increases in the intensity
      of medication in terms of defined daily doses per patient, rather than a larger
      number of patients starting drug treatment. Real prices decreased during the 10
      year study period. We found large differences between ATC groups in terms of
      spending growth. The ATC groups that have contributed the most to the increase in
      spending are: drugs that affect the CNS (N), the alimentary tract and metabolism
      (A) and the cardiovascular system (C), which are also the three largest groups in
      terms of sales. For all three groups, it was the residual that mainly drove
      costs. CONCLUSION: This study indicates very clearly that the main driving force
      behind the increase in drug costs in Sweden between 1990 and 2000 was the change
      in drug therapy from old to new and more innovative and expensive drug therapies.
      This shows the importance of carrying out economic evaluations of new more costly
      drugs in order to make an assessment of the social benefits of a switch from a
      cheaper to a more expensive drug.

PMID- 14720081
TI  - A multicentre study of patient survival, disability, quality of life and cost of
      care: among patients with AIDS in northern Italy.
AB  - OBJECTIVE: To describe the epidemiological, clinical and economic changes that
      occurred in the HIV epidemic in Italy prior to and after the introduction of
      highly active antiretroviral therapy (HAART). DESIGN: A prospective,
      observational, multicentre case-control study was conducted comparing data,
      collected over 6 months, from an AIDS cohort in 1998 with that of a cohort in
      1994. Out of 77 patients with AIDS in the 1998 cohort, 74 survived. These 74
      patients were matched for severity of illness with 74 patient survivors from the
      1994 cohort to enable valid comparisons of mortality, disability-dependency (DD),
      health-related QOL (HR-QOL), and direct costs. RESULTS: Overall, a considerable
      difference was observed in mortality (33.8% in 1994 vs 3.9% in 1998) between
      unmatched patients of the two cohorts. As for matched patients, the number of
      hospital admissions was 1.7 in 1994 and 0.8 in 1998; the average length of stay
      was 28.1 days in 1994 and 12.6 days in 1998. The direct cost per patient per year
      was euro15 390 and euro11 465 for the 1994 and 1998 cohorts, respectively (1999
      values). The 1998 patient cohort had significantly better HR-QOL at 6 months in
      two domains of the instrument used (emotional reaction and energy) and the
      percentage of totally dependent patients was significantly lower compared with
      the 1994 cohort (1.4% vs 6.8%). CONCLUSIONS: This is the first study to present a
      comprehensive comparison of direct costs, DD and HR-QOL of patients with AIDS
      between two time periods. The use of a case-control design has enabled changes in
      costs and outcomes to be linked to the introduction of HAART in Italy in 1997.

PMID- 14720082
TI  - Allocation of resources between smoking cessation methods and lovastatin
      treatment of hypercholesterolaemia: based on cost effectiveness and the social
      welfare function.
AB  - OBJECTIVE: To use the social welfare function to decide on allocation of
      resources between smoking cessation methods and lovastatin treatment of
      hypercholesterolaemia for the primary prevention of coronary heart disease.
      METHOD: Three smoking cessation therapies (medical advice, nicotine gum and
      nicotine patch) were considered in smokers, and lovastatin 20, 40 and 80 mg/day
      was considered in individuals with hypercholesterolaemia (total cholesterol >
      7.24 mmol/L [> 270 mg/dL]). Multiple logistic regression analysis was used to
      obtain parameter epsilon determining the exact form of the social welfare
      function in Catalonia, Spain. The preferable strategy was to give higher priority
      to the intervention that used one smoking cessation method and lovastatin
      treatment for hypercholesterolaemia and that was associated with a value of
      epsilon consistent with the social welfare function. RESULTS: A value of 1.58
      (95% CI: 0.75-2.84) was obtained for parameter epsilon of the social welfare
      function, showing a nonutilitarian form. A higher priority should be given, based
      on the social welfare function, to the intervention using medical advice for
      smoking cessation and lovastatin 20-80 mg/day for hypercholesterolaemia, since
      this approach was associated with epsilon values of 2.8-2.9 in men and 1.8-2.4 in
      women, while interventions using nicotine substitution therapies were associated
      with epsilon values of < 0.9 in men and < 0.4 in women. The cost of treating all
      smokers and individuals with hypercholesterolaemia was 35% lower using medical
      advice for smoking cessation and lovastatin 20 mg/day, which was associated with
      epsilon values of 2.9 in men and 2.4 in women, than using a utilitarian solution
      consisting of nicotine patches for smoking cessation and lovastatin 20 mg/day.
      CONCLUSION: These results show that higher priority should be given to lovastatin
      treatment of hypercholesterolaemia than to nicotine substitution treatments for
      smoking cessation, based on cost effectiveness and the social welfare function.
      The study also showed the applicability of this method to decisions about
      resource allocation between competing treatments when society has a
      nonutilitarian social welfare function.

PMID- 14720079
TI  - Cost-effective strategies in the prevention of diabetic nephropathy.
AB  - A significant subgroup of patients with diabetes mellitus are predisposed to
      developing diabetic nephropathy and it is in this subgroup that other diabetes-
      related complications, and in particular greatly increased cardiovascular disease
      risk, are concentrated. The high personal, social and financial costs of managing
      end-stage renal failure and the other complications associated with diabetic
      nephropathy make a powerful case for screening and effective intervention
      programmes to prevent the condition or retard its progression. As major
      breakthroughs in finding genetic susceptibility factors remain elusive, screening
      efforts continue to be based on microalbuminuria testing, despite increasing
      recognition of its limitations as a positive predictor of nephropathy.
      Interventions have been extensively studied, but results remain conflicting.
      Economic evaluations of such screening and intervention programmes are essential
      for health planners, yet models of the cost/benefit ratio of such interventions
      often rely on a rather slim evidence base. Where economic models are developed,
      they are frequently based on those papers that propound the greatest clinical
      benefits of a given intervention, leading to a possible over-estimation of the
      advantages of the chosen approach. Furthermore, the benefits of even such
      generally accepted interventions as ACE inhibitor treatment are less firmly
      established than generally appreciated. Lifestyle interventions are instinctively
      attractive, but are by no means a low-cost option (as is often assumed by both
      medical professionals and politicians). This review critically assesses the
      evidence for clinical efficacy and economic benefit of microalbuminuria screening
      and interventions such as intensive glycaemic control, antihypertensive
      treatment, ACE inhibition and angiotensin receptor blockade, dietary protein
      restriction and lipid-modifying therapy. The various costs associated with
      diabetic nephropathy are so great that even expensive interventions may have a
      favourable cost/benefit ratio, provided they are truly effective.

PMID- 14720083
TI  - Regulatory perspectives on data safety monitoring boards: protecting the
      integrity of data.
AB  - The use of interim analyses and data safety monitoring boards (DSMBs) can assist
      greatly in the timely determination of whether or not a medicine has an
      acceptable benefit-risk profile. Regulatory authorities regard the appropriate
      use of interim analyses favourably, but will consider the extent to which the
      conduct of interim analyses and the involvement of DSMBs may have compromised the
      evidence of efficacy and safety from a clinical trial. Issues of particular
      concern, which may potentially introduce bias, include the dissemination of
      interim data and the rules by which a trial might be terminated early. If data
      from trials which employ a DSMB are to be considered reliable and scientifically
      valid, it is the responsibility of the trial sponsor to demonstrate that the DSMB
      is set up and run appropriately and to verify that any bias introduced has had no
      important effect on the conclusions.

PMID- 14720084
TI  - Management of chronic hepatitis C in patients co-infected with HIV: focus on
      safety considerations.
AB  - Hepatitis C virus (HCV) infection is a significant public health problem and one
      of the most important causes of chronic liver disease worldwide. Co-infection
      with HCV and HIV occurs frequently, mainly because both viruses share the same
      transmission routes. In recent years, the life expectancy of patients with HIV
      disease has been increased due to the introduction of highly active
      antiretroviral therapy (HAART). Furthermore, several studies have established
      that HIV infection is associated with a major progression of the HCV-related
      liver disease. Thus, end-stage liver disease has become a leading cause of
      morbidity and mortality in this population, emphasising the importance of
      treatment of chronic hepatitis C in HIV-infected persons. The biological and
      histological benefit of interferon-alpha (IFNalpha) therapy in patients co
      infected with HCV/HIV is not significantly different from that noted in similar
      patients without HIV when the HIV infection is adequately controlled. However,
      patients with low CD4+ cell counts tend to respond poorly to anti-HCV
      therapy.Given the relatively low sustained virological response rate to IFN
      alone, the use of IFNalpha monotherapy has been largely abandoned in favour of
      combination therapy with ribavirin. In the last 2 years, IFN plus ribavirin
      combination therapy has been the standard care for the treatment of chronic
      hepatitis C. Although information on the safety and efficacy of this dual therapy
      in HCV/HIV co-infected patients is scarce, recent trials have reported that the
      combination of IFN plus ribavirin is well tolerated and feasible in patients co
      infected with HCV/HIV. However, the rates of sustained virological response seem
      to be worse than those observed in patients without HIV infection. New IFN
      formulations (e.g. pegylated interferon) plus ribavirin appear to be way of the
      future for the treatment of chronic hepatitis C in patients both with and without
      HIV co-infection.

PMID- 14720087
TI  - Is aspirin a cause of Reye's syndrome?

PMID- 14720086
TI  - Failure to continue lipid-lowering drug use following the withdrawal of
      cerivastatin.
AB  - BACKGROUND: Persistence with lipid-lowering drug use is important in order for
      patients to gain full treatment benefit. The withdrawal of cerivastatin from the
      market may have affected persistence due to the fear of serious adverse effects.
      OBJECTIVE: To assess failure of patients to continue lipid-lowering drug use
      following the withdrawal of cerivastatin. METHODS: A cohort study including 3.5
      months follow-up after the withdrawal of cerivastatin in August 2001 was
      conducted using data from community pharmacies in The Netherlands, covering a
      population of approximately 600,000 subjects. Patients selected for inclusion in
      the index group were current users of cerivastatin on August 10, 2001 (the date
      that cerivastatin was withdrawn from the market). Reference patients were gender,
      age and pharmacy or region matched patients who were using any HMG-CoA reductase
      inhibitor other than cerivastatin on the same date. The main outcome measure was
      discontinuation of lipid-lowering drug use. To assess whether discontinuation had
      increased in the reference group, discontinuation rates were compared with
      discontinuation rates in the previous year. Data on these rates in 2000 were
      obtained from the population-based PHARMO record linkage system. RESULTS: A total
      of 31 pharmacies of the research network (response rate 86.1%) provided
      medication histories of 234 current users of cerivastatin and 431 matched
      patients using any other HMG-CoA reductase inhibitor. In addition, 352 current
      users of cerivastatin and 704 matched patients using any other HMG-CoA reductase
      inhibitor were obtained from the PHARMO database. Overall, 13.7% of subjects in
      the cerivastatin group (n=586) and 9.5% in the reference group (n=1135)
      discontinued lipid-lowering medication (adjusted odds ratio [OR] 1.44; 95% CI
      1.04-2.00). The rate of discontinuation in the reference group was comparable to
      this rate in the previous year. Discontinuation was more prevalent in women who
      had been taking cerivastatin (adjusted OR 1.74; 95% CI 1.09-2.78), those
      receiving low doses of cerivastatin (adjusted OR 2.45; 95% CI 1.20-4.97), those
      who received their last cerivastatin prescription from a specialist (adjusted OR
      1.92; 95% CI 1.02-3.60) and those who had recently started using cerivastatin
      (adjusted OR 2.80; 95% CI 0.98-7.98), although the latter was not statistically
      significant. CONCLUSIONS: Failure to continue lipid-lowering drug use was higher
      in patients using cerivastatin than in users of other HMG-CoA reductase
      inhibitors, especially in women, those using low doses of HMG-CoA reductase
      inhibitors and recent starters of lipid-lowering medication. The prevention of
      unwarranted discontinuation of drugs due to market withdrawal should be a joint
      task of healthcare providers, industry and regulatory bodies.

PMID- 14720089
TI  - Changing patterns in living arrangements of Medicaid long-term care recipients
      with ID/DD between 1992 and 2002.

PMID- 14720091
TI  - Curiosity and mental retardation: beyond IQ.

PMID- 14720092
TI  - Life story work: an important, but overlooked, instrument.

PMID- 14720085
TI  - Antimalarial drug toxicity: a review.
AB  - Malaria, caused mostly by Plasmodium falciparum and P. vivax, remains one of the
      most important infectious diseases in the world. Antimalarial drug toxicity is
      one side of the risk-benefit equation and is viewed differently depending upon
      whether the clinical indication for drug administration is malaria treatment or
      prophylaxis. Drug toxicity must be acceptable to patients and cause less harm
      than the disease itself. Research that leads to drug registration tends to omit
      two important groups who are particularly vulnerable to malaria--very young
      children and pregnant women. Prescribing in pregnancy is a particular problem for
      clinicians because the risk-benefit ratio is often very unclear. The number of
      antimalarial drugs in use is very small. Despite its decreasing efficacy against
      P. falciparum, chloroquine continues to be used widely because of its low cost
      and good tolerability. It remains the drug of first choice for treating P. vivax
      malaria. Pruritus is a common adverse effect in African patients. As prophylaxis,
      chloroquine is usually combined with proguanil. This combination has good overall
      tolerability but mouth ulcers and gastrointestinal upset are more common than
      with other prophylactic regimens. Sulfadoxine/pyrimethamine is well tolerated as
      treatment and when used as intermittent preventive treatment in pregnant African
      women. Sulfadoxine/pyrimethamine is no longer used as prophylaxis because it may
      cause toxic epidermal necrolysis and Stevens Johnson syndrome. Mefloquine remains
      a valuable drug for prophylaxis and treatment. Tolerability is acceptable to most
      patients and travellers despite the impression given by the lay press. Dose
      related serious neuropsychiatric toxicity can occur; mefloquine is
      contraindicated in individuals with a history of epilepsy or psychiatric disease.
      Quinine is the mainstay for treating severe malaria in many countries.
      Cardiovascular or CNS toxicity is rare, but hypoglycaemia may be problematic and
      blood glucose levels should be monitored. Halofantrine is unsuitable for
      widespread use because of its potential for cardiotoxicity. There is renewed
      interest in two old drugs, primaquine and amodiaquine. Primaquine is being
      developed as prophylaxis, and amodiaquine, which was withdrawn from prophylactic
      use because of neutropenia and hepatitis, is a potentially good partner drug for
      artesunate against falciparum malaria. Atovaquone/proguanil is a new antimalarial
      combination with good efficacy and tolerability as prophylaxis and treatment. The
      most important class of drugs that could have a major impact on malaria control
      is the artemisinin derivatives. They have remarkable efficacy and an excellent
      safety record. They have no identifiable dose-related adverse effects in humans
      and only very rarely produce allergic reactions. Combining an artemisinin
      derivative with another efficacious antimalarial drug is increasingly being
      viewed as the optimal therapeutic strategy for malaria.

PMID- 14720093
TI  - Will the real elephant please stand up?

PMID- 14720094
TI  - Friendships between persons with and without developmental disabilities.
AB  - Interpersonal connections, friendships, and belonging play important roles in a
      person's emotional and physical well-being. However, recent studies reveal that
      persons with developmental disabilities often live with few connections and
      friendships within unwelcoming communities. Through this qualitative study, we
      enter this relatively unexplored area of friendships between persons with and
      without developmental disabilities by interviewing four existing friendship dyads
      in the intentional community of L'Arche. In this research these friendships are
      described, factors that foster or inhibit their development are identified, and
      communal influences on the relationships are discussed.

PMID- 14720095
TI  - Alienated advocacy: perspectives of Latina mothers of young adults with
      developmental disabilities on service systems.
AB  - Although collaborative partnership between parents and professionals is a
      cornerstone of the special education and service systems, this relationship
      exists more as an ideal, especially when low-income, culturally diverse families
      are involved. Through three focus groups, we examined the beliefs of 16 low
      income Latina mothers of young adults with developmental disabilities about their
      relationships with the educational and service delivery systems. Primary concerns
      identified were (a) poor communication, (b) low effort in providing services, (c)
      negative attitudes of professionals toward the client-children, (d) negative
      treatment of parents by professionals, and (e) the mother's role as central to
      the well-being of her child. Mothers tended to adopt a posture of alienated
      advocacy in relation to their child's educational and service needs.

PMID- 14720096
TI  - Attitudes of American and Israeli staff toward people with intellectual
      disabilities.
AB  - We compared the inclusion-related attitudes of community agency staff in the
      United States and Israel. Samples of 147 (United States) and 74 (Israel) staff
      members were assessed with the Community Living Attitudes Scale (CLAS). Results
      showed that higher educational levels, regardless of nation, were associated with
      higher Empowerment scores, lower Exclusion scores, lower Sheltering scores, and
      higher Similarity scores. Empowerment attitudes were strongly related to
      differences in the agencies in which individuals were employed. Controlling for
      age, education, and agency, we found that staff in the United States had higher
      Empowerment scores than did Israeli staff. Israeli staff had higher Sheltering
      and Similarity scores and marginally higher Exclusion scores than did the United
      States staff.

PMID- 14720097
TI  - Cultural context of caregiving: differences in depression between Puerto Rican
      and non-Latina White mothers of adults with mental retardation.
AB  - Differences in depression between Puerto Rican and non-Latina White mothers
      providing care to their adult child with mental retardation were examined. The
      focus of this study is on how family problems may mediate the effect of the
      adult's behavior problems on the mother's level of depressive symptoms and how
      this process differs across the two groups of mothers. As hypothesized, family
      problems was a stronger predictor of depressive symptoms for Puerto Rican mothers
      than for non-Latina White mothers. In addition, Puerto Rican mothers were in
      poorer physical health, which further accounted for differences in depression
      between the two groups.

PMID- 14720098
TI  - South Asian Indian cultural orientations toward mental retardation.
AB  - The findings of a portion of a 2-year ethnographic study involving North Indian
      Hindu immigrants living in the mid-Western United States is discussed. These
      findings illuminate the ways in which participants think and talk about mental
      retardation, how this linguistic information was obtained, and the cultural
      context within which participants have come to hold their beliefs. Implications
      for special education practice are explored as are some strategies that could be
      helpful when working with Indian families. Suggestions for future research are
      included.

PMID- 14720100
TI  - Evaluating the efficiency of treatment in the allergic rhinitis market.
AB  - BACKGROUND: In the present era of increasing health care expenditures, economic
      comparisons of therapeutic products play an important role in ensuring that
      limited health care resources are used appropriately. OBJECTIVE: To provide a
      model for the comparative analysis of alternative treatments, in terms of both
      cost and efficacy, in allergic rhinitis that will provide decision makers in a
      managed care environment an additional tool to help maximize health care benefit
      per dollar spent. We also review current treatments in the allergic rhinitis
      market and their impact on cost, availability, and utilization. SUMMARY: Efficacy
      estimates were derived from published reviews, meta-analyses, and guidelines, and
      cost data are based on average wholesale prices. Our results indicate that when
      cost and efficacy data are plotted on a cost-effectiveness plane, the intranasal
      corticosteroids appear to be the most efficient use of health care resources.
      Moreover, budesonide aqueous nasal spray was found to be the most efficient
      treatment for allergic rhinitis when compared with 3 other leading intranasal
      corticosteroids used at their recommended starting doses, the less
      sedating/nonsedating antihistamines, and a leukotriene receptor antagonist.
      CONCLUSION: Evaluating products on an efficiency frontier platform, which
      integrates both the effectiveness and cost of products, will allow health plan
      decision makers to ensure the appropriate allocation of health care resources.

PMID- 14720101
TI  - Cost efficiency of intranasal corticosteroid prescribing patterns in the
      management of allergic rhinitis.
AB  - BACKGROUND: Effective treatment of seasonal or perennial allergic rhinitis often
      requires use of topical intranasal corticosteroids (INSs). Despite differences in
      recommended starting dosages, the 4 leading INSs by market share are packaged in
      bottles containing 120 metered-dose sprays. OBJECTIVE: To determine the relative
      prescribed dosages of the leading INSs and compare economic differences resulting
      from these prescribing behaviors. METHODS: The IMS National Disease and
      Therapeutic Index (NDTI) was used to identify prescribing habits for the 4
      leading INSs: fluticasone propionate nasal spray (FPNS), mometasone furoate
      aqueous nasal spray (MFNS), triamcinolone acetonide aqueous nasal spray (TANS),
      and budesonide aqueous nasal spray (BANS). The NDTI uses a national, randomly
      drawn, 2-stage stratified clustersampling methodology. Physicians are sampled
      during the first stage, with 2 workdays per month subsampled from each physician
      in the second stage. Each physician reports on all patient contacts during the 2
      consecutive days, offering a continuing compilation of statistical information
      about patterns and treatment of disease encountered by office-based physicians.
      In a given month, the NDTI reports on 1180 unique physicians. RESULTS: From
      January 1, 2002, to December 31, 2002, 58% of prescriptions for FPNS were for 4
      sprays daily with 37% for 2 sprays daily, MFNS: 44% for 4 sprays and 52% for 2,
      TANS: 65% for 4 sprays and 31% for 2, and BANS: 29% for 4 sprays and 68% for 2.
      These equated to mean prescribed daily dosages of 3.47 sprays per day for FPNS,
      3.33 for MFNS, 3.50 for TANS, and 2.73 for BANS. Because each INS is packaged in
      a bottle with 120 metered-dose sprays, the differences in dosage offer varying
      days of supply per unit filled. BANS offered the most days of treatment (44
      days), followed by MFNS (38 days) and FPNS and TANS (means of 35 and 34 days,
      respectively) per single prescription filled. Cost per day of treatment was
      calculated by multiplying the prescribed dosage with the average wholesale price
      of the products. BANS had the lowest cost per day of treatment at US dollars
      1.54, with each other INS costing at least an additional US dollars 0.26 daily
      (MFNS US dollars 1.80; FPNS US dollars 1.88; TANS US dollars 1.97). CONCLUSION:
      Based on physician prescribing patterns of INSs from the NDTI database, BANS
      offers more days of treatment at a lower cost per day than other leading INSs.

PMID- 14720102
TI  - Acute uncomplicated UTI and E. coli resistance: implications for first-line
      empirical antibiotic therapy.
AB  - BACKGROUND: Uncomplicated urinary tract infection (uUTI) typically affects
      immunocompetent, anatomically normal women. Escherichia coli (E. coli) accounts
      for approximately 80% of cases. Given increased E. coli
      trimethoprimsulfamethoxazole (TMP-SMX) resistance, practice guidelines advocate
      first-line alternatives based on local resistance rates above 10%. This paper
      provides a model incorporating use of a new extended-release formulation of
      ciprofloxacin, used once daily, to facilitate revision of uUTI treatment policies
      by managed care organizations (MCOs) and practitioners. METHODS: A cost
      minimization model was designed from the MCO perspective, assuming an initial
      office visit with a urinalysis and empiric, 3-day treatment (TMP-SMX 800/160 mg
      twice daily or ciprofloxacin XR 500 mg once daily). Persistent infections were
      assumed to require a second visit. Costs were provided by a major employee health
      and benefit plan provider; clinical data were based on published information.
      Five case scenarios were used to compare average treatment costs based on varying
      E. coli resistance rates to therapy and to identify rates of TMP-SMX resistance
      where total treatment costs are equal. RESULTS: Using national surveillance
      resistance data, Case 1 demonstrated average cost savings of 9.59 dollars to
      10.21 dollars with ciprofloxacin XR. In Case 2, treatment costs (49.19 dollars)
      were equal at an E. coli resistance rate of 4.3% for TMP-SMX and 1.0% for
      ciprofloxacin. Case 3 assumed empiric telephone prescribing, demonstrating that,
      at 4.3% TMP-SMX resistance, costs are equal for both treatments (4.19 dollars).
      Case 4 used real-world data on therapy duration, demonstrating that, at 2.8% TMP
      SMX resistance, costs are equal for both treatments (54.87 dollars). Case 5
      assumed 10% ciprofloxacin-E. coli resistance; at 13.3% TMP-SMX resistance,
      treatment costs were equal (57.50 dollars). Results from all cases demonstrate
      that while the per-dose cost of ciprofloxacin XR far exceeds TMP-SMX, average
      total treatment costs are lower for ciprofloxacin XR at expected local levels of
      E. coli resistance to TMP-SMX. CONCLUSIONS: The results suggest that in areas
      where local TMP-SMX E. coli resistance exceeds 10% and resistance to
      ciprofloxacin remains low, (0.5% to 6%) ciprofloxacin XR is an appropriate
      alternative to standard empiric treatment. The data provide evidence to MCOs that
      switching to a more expensive per-dose alternative will not necessarily increase
      total costs when guideline recommendations are followed. Responsible use of
      antibiotics for uUTI requires selection and administration of the right dosage of
      the most suitable antibiotic for an appropriate time period to eliminate
      pathogens quickly and successfully. The decision to use an alternative first-line
      therapy for uUTI should be driven by local resistance and susceptibility data-
      not simply per-dose drug acquisition costs.

PMID- 14720103
TI  - Markov modeling analysis of health and economic outcomes of therapy with
      valsartan versus amlodipine in patients with type 2 diabetes and
      microalbuminuria.
AB  - OBJECTIVE: To estimate 8-year health and economic outcomes of the angiotensin II
      receptor blocker valsartan versus the calcium channel blocker amlodipine in
      therapy of patients with type 2 diabetes and microalbuminuria based on clinical
      endpoints from a 6-month randomized controlled clinical trial, the
      MicroAlbuminuria Reduction With VALsartan (MARVAL) study. METHODS: We developed a
      Markov model that utilized urinary albumin excretion rate data to project patient
      distributions to 7 possible health states over 8 years. For each health state, we
      identified quality-adjustment weights (health utilities) and medical care costs
      from public sources. The model then calculated mean quality-adjusted survival,
      medical care costs, and cost-effectiveness ratios for each treatment arm.
      Treatment arms were compared with the incremental cost-effectiveness ratio.
      RESULTS: Patients treated with valsartan gained 7 months (mean) per patient of
      quality-adjusted survival relative to patients treated with amlodipine (77 versus
      70 months; P<0.01); valsartan patients also incurred 32,412 dollars (mean) per
      patient lower medical costs than amlodipine patients (92,058 dollars versus
      124,470 dollars; P<0.01). Model results were consistent for each year of analysis
      and robust to changes in key model parameters. CONCLUSION: This research (1)
      extends 6-month clinical trial outcomes to an 8-year period, (2) translates
      health outcomes from technical clinical endpoints to quality-adjusted survival,
      and (3) estimates economic consequences of therapeutic outcomes. The results
      quantify the favorable long-term health (i.e., quality-adjusted survival) and
      economic benefits (i.e., lower total medical costs) of therapy with valsartan, an
      angiotensin II receptor blocker, versus amlodipine, a calcium channel blocker, in
      the treatment of patients with type 2 diabetes and microalbuminuria based on an
      extension of the results of a short-term clinical (MARVAL) trial. These research
      findings are important to the extent patients with type 2 diabetes and
      microalbuminuria do not receive the recommended antihypertensive agents that
      block the renin-angiotensin system (angiotensin-converting enzyme inhibitors or
      angiotensin II receptor blockers).

PMID- 14720104
TI  - Clinical monograph: hormone replacement therapy.
AB  - BACKGROUND: For decades, hormone replacement therapy (HRT), which includes both
      estrogen and progestin, has been administered to postmenopausal women to mainly
      treat the symptoms of menopause and help prevent osteoporosis, with the added
      benefit of preventing coronary heart disease (CHD). Recently released study
      results have left clinicians wondering if HRT should be used at all, and, if so,
      with whom and under what circumstances. OBJECTIVE: To provide readers with an
      example of the real-world operation of a pharmacy and therapeutics (P&T)
      committee in its use of a concise clinical monograph to guide its formulary
      decisions. METHODS: The most relevant information for this committee, interested
      in evidence, was an analysis of the most current pivotal trials and observational
      studies that help define the place in therapy of HRT and provide information on
      product efficacy and safety. These included the Heart and Estrogen/progestin
      Replacement Study (HERS) and its extension trial, HERS II, in postmenopausal
      women with CHD and an average age of 67 years. The Women's Health Initiative
      (WHI) study, where the mean age of postmenopausal women was 63 years was also
      reviewed. The U.S. Food and Drug Administration (FDA) statements through January
      8, 2003, on the appropriate use of these agents were also included in this
      clinical monograph for P&T committee review. RESULTS: HERS and HERS II provided
      evidence that HRT does not provide secondary prevention in women with CHD. Data
      from the WHI study concluded that HRT promotes CHD and breast cancer in this age
      group. The Women's Health, Osteoporosis, Progestin, Estrogen study concluded that
      lower doses of conjugated estrogens (0.3 mg) are just as effective in treating
      postmenopausal symptoms as higher doses (0.625 mg) and result in fewer side
      effects. CONCLUSION: The risk of breast cancer outweighs the benefits of
      osteoporosis prevention from HRT. According to labeling changes recommended by
      the FDA, HRT (or estrogen replacement therapy) should be limited to the shortest
      possible duration. Alternatives to HRT should be considered for the prevention of
      postmenopausal osteoporosis.

PMID- 14720105
TI  - Cost-effectiveness analysis and the formulary decision-making process.
AB  - BACKGROUND: Faced with high drug expenditures in an environment of cost
      containment, drug formulary systems, particularly in managed care, have become
      more dependent on pharmacoeconomic evaluations to assess the value of new
      products. Within pharmacoeconomics (PE), cost-effectiveness analysis (CEA) is the
      most commonly used method. However, current methodological concerns about CEA
      have limited its practical contribution to the formulary process. Advances in
      analysis are likely to improve the relevance of CEA over time. OBJECTIVE: The
      purpose of this paper is to review CEA, its limitations, and its applications in
      formulary decision making in order to promote greater utility of CEA for managed
      care pharmacists. SUMMARY: Enhancements to CEA, such as the development of
      modeling software, rank-order stability analysis, cost-consequence analysis
      (CCA), and budget impact analysis are discussed. A combined method of CCA-CEA and
      standardized guidelines are suggested to improve the impact of CEA in the drug
      formulary process. CONCLUSION: Along with advances in its methodology and
      relevant standardized guidelines, CEA will gain increased importance in formulary
      decision making, helping to assure the goal of cost containment while ensuring
      quality of care.

PMID- 14720106
TI  - Framework for pharmacy services quality improvement--a bridge to cross the
      quality chasm. Part I. The opportunity and the tool.
AB  - OBJECTIVE: To review the literature on the subject of quality improvement
      principles and methods applied to pharmacy services and to describe a framework
      for current and future efforts in pharmacy services quality improvement and
      effective drug therapy management. BACKGROUND: The Academy of Managed Care
      Pharmacy produced the Catalog of Pharmacy Quality Indicators in 1997, followed by
      the Summary of National Pharmacy Quality Measures in February 1999. In April
      2002, AMCP introduced Pharmacy's Framework for Drug Therapy Management in the
      21st Century. The Framework documents include a self-assessment tool that details
      more than 250 specific "components" that describe tasks, behaviors, skills,
      functions, duties, and responsibilities that contribute to meeting customer
      expectations for effective drug therapy management. FINDINGS: There are many
      opportunities for quality improvement in clinical, service, and cost outcomes
      related to drug therapy management. These may include patient safety; incidence
      of medical errors; adverse drug events; patient adherence to therapy; attainment
      of target goals of blood pressure, glucose, and lipid levels; risk reduction for
      adverse cardiac events and osteoporotic-related fractures; patient satisfaction;
      risk of hospitalization or mortality; and cost of care. Health care practitioners
      can measure improvements in health care quality in several ways including (a) a
      better patient outcome at the same cost, (b) the same patient outcome at lower
      cost, (c) a better patient outcome at lower cost, or (d) a significantly better
      patient outcome at moderately higher cost. Measurement makes effective management
      possible. A framework of component factors (e.g., tasks) is necessary to
      facilitate changes in the key processes and critical factors that will help
      individual practitioners and health care systems meet customer expectations in
      regard to drug therapy, thus improving these outcomes. CONCLUSIONS: Quality
      improvement in health care services in the United States will be made in
      incremental changes that rely on a structure-process-outcome model. The structure
      is provided by evidence created from controlled randomized trials and other
      studies of care and system outcomes that are based on the scientific method. The
      process portion is created by the application of evidence in the form of clinical
      practice guidelines, clinical practice models, and self-assessment tools such as
      Pharmacy's Framework for Drug Therapy Management. Incremental changes in
      structure and process will result in the desirable outcome of meeting customer
      needs for more effective drug therapy and disease management.

PMID- 14720107
TI  - Evaluating the cost-effectiveness of statins.

PMID- 14720108
TI  - Challenges in evaluating the cost-effectiveness of statins.

PMID- 14720109
TI  - 3-tier drug benefit designs based on sound drug formulary principles will
      maximize favorable outcomes.

PMID- 14720110
TI  - Managed care pharmacy--weighing clinical, service, and cost outcomes.

PMID- 14720111
TI  - Drug formulary decisions--evaluating the risks and benefits of hormone
      replacement therapy.

PMID- 14720112
TI  - The optometrist's role in learning difficulties and dyslexia.

PMID- 14720113
TI  - Neural underpinnings of dyslexia as a disorder of visuo-spatial attention.
AB  - For nearly 100 years, the underlying cause of dyslexia has been a matter of much
      debate, with widely varying viewpoints that have ranged from considering dyslexia
      as largely a learning disability to claims that it is essentially a perceptual
      defect occurring early along the visual pathway. This paper reviews some of this
      literature with particular reference to the studies that have implicated a defect
      in the afferent visual pathways in the aetiology of the disorder, then goes on to
      outline a neural theory of how functionally distinct parallel pathways in vision
      interact with each other in the process of reading and suggests how a defect in
      these pathways can lead to reading difficulties. Central to the proposed scheme
      is the suggestion that a fast-track pathway, arising from the magnocellular cells
      in the retina and acting through an attentional mechanism, has a gating function
      in spotlighting the individual letters of a text in a sequential fashion. That
      such gating occurs at the level of the primary visual cortex is supported by
      recent physiological evidence concerning attentional mechanisms.

PMID- 14720114
TI  - Blepharoptosis in RGP and PMMA hard contact lens wearers.
AB  - BACKGROUND: Contact lens wear has been documented to cause an acquired non-senile
      blepharoptosis. This is generally associated with prolonged wearing of hard
      contact lenses. The aim of this study was to determine the clinical features of
      blepharoptosis associated with contact lens wear including the type of contact
      lens and the duration of wear. METHODS: This is a retrospective study of
      consecutive patients seen over four years (1997 to 2001) in the private practice
      of an oculoplastic surgeon. RESULTS: A total of 15 consecutive patients presented
      over the four-year period with blepharoptosis in the context of prolonged contact
      lens use. Four of the 15 patients (27 per cent) were wearing rigid gas permeable
      (RGP) lenses. The rest had been wearing PMMA hard lenses. Thirteen patients (87
      per cent) had been wearing their contact lenses for more than 17 years. The
      patients' ages ranged between 15 and 71 years with a mean age of 46 years. All 15
      patients had normal levator palpebrae superioris function. Four patients (27 per
      cent) had bilateral involvement. Eleven patients (73 per cent) underwent ptosis
      repair where aponeurosis thinning/dehiscence was noted. When compared with
      patients who presented over the same period with other causes of blepharoptosis
      (traumatic, myopathic, anophthalmic and involutional), contact lens wear was
      found to be an uncommon cause of ptosis across all age groups. CONCLUSION: The
      majority of contact lens wearers presenting with blepharoptosis gave a history of
      prolonged use of hard contact lenses. One explanation for this would be the
      mechanisms of removal of hard contact lenses. This involves pulling the lids
      laterally at the lateral canthus followed by a harsh blink, which over years can
      lead to levator aponeurosis dehiscence. Contact lens associated ptosis is an
      uncommon cause of acquired ptosis across all age groups.

PMID- 14720115
TI  - Inter-observer variability of central corneal thickness measurements using non
      contact specular microscopy after laser in situ keratomileusis.
AB  - BACKGROUND: The aim of this study was to investigate the inter-observer
      variability of central corneal thickness measurements carried out with a non
      contact specular microscope in patients who had undergone myopic laser in situ
      keratomileusis. METHODS: Twenty-six eyes of 26 subjects who had undergone myopic
      laser in situ keratomileusis were studied with the Topcon SP-2000P non-contact
      specular microscope (Topcon Corp, Tokyo, Japan). The mean of three consecutive
      measurements of the central corneal thickness was recorded by two investigators
      prior to and one month after myopic laser in situ keratomileusis. Results
      obtained by each of the two physicians were compared. RESULTS: Prior to surgery
      the mean central corneal thickness was 536.2 +/- 22.2 microm for physician 1 and
      536.3 +/- 22.2 microm for physician 2 (p = 0.980). The pre-operative 95 per cent
      confidence interval was 522.7 to 544.2 microm (physician 1) and 523.1 to 544.1
      microm (physician 2). The mean central corneal thickness was 485.8 +/- 29.3
      microm for physician 1 and 485.6 +/- 28.0 micro m for physician 2 one month after
      laser in situ keratomileusis (p = 0.977). The post-operative 95 per cent
      confidence intervals were 470.1 to 496.2 microm and 470.3 to 495.4 microm for
      physicians 1 and 2, respectively. CONCLUSION: Central corneal thickness
      measurements can be carried out by different clinicians after laser in situ
      keratomileusis with non-contact specular pachymetry, without there being any
      significant differences among them.

PMID- 14720116
TI  - Use of silicone hydrogel contact lenses by Australian optometrists.
AB  - BACKGROUND: Prior to the launch of silicone hydrogel (Si-H) materials in
      Australia in 1999, only 1.6 per cent of lenses were prescribed on a continuous
      wear basis. METHODS: One thousand surveys were distributed randomly to
      practitioners in Australia during January 2000, 2001 and 2002 (total surveys
      3000). Each anonymous survey requested data about the next 10 patients fitted
      with contact lenses, including date, age, gender, new fitting or refitting, lens
      material type, lens design, frequency of replacement, modality of wear, uses per
      week and care regimen. RESULTS: Twenty per cent (599) were returned, reporting
      data on 5976 fittings. A total of 710 fittings used Si-H contact lenses (11.9 per
      cent), which represented 18.6 per cent of all soft lens fittings. During the
      three years, the proportion of practitioners prescribing Si-H lenses increased
      from 42.2 to 52.5 per cent. In 2000, 43.8 per cent were daily wear, which
      decreased to 32.2 per cent by 2002. The solution system of choice for daily wear
      lenses was multipurpose solutions (98.4 per cent); the only alternative was
      hydrogen peroxide systems. Continuous wear represented 11.7 per cent of all
      fittings, of which 85.7 per cent were Si-H, 3.0 per cent RGP lenses and 11.3 per
      cent conventional hydrogels. For continuous wear, 79.0 per cent of fittings were
      to existing wearers, whereas for daily wear, 59.4 per cent were existing wearers.
      More males were prescribed Si-H continuous wear contact lenses, while females
      were more likely to be prescribed Si-H on a daily wear basis. DISCUSSION: Si-H
      contact lenses were introduced to the Australian market as a continuous wear
      contact lens, yet many practitioners use this product for daily wear with
      multipurpose solutions. By 2002, more practitioners were prescribing Si-H contact
      lenses for continuous wear than in 2000, suggesting a growing confidence in that
      product for that mode of wear. A comparison with an earlier survey shows there is
      an increase in continuous wear from 1.6 per cent to 11.7 per cent over a five
      year period.

PMID- 14720117
TI  - Is ascorbate in human tears from corneal leakage or from lacrimal secretion?
AB  - BACKGROUND: This study investigated whether fresh main lacrimal gland secretion
      contains ascorbate, with a view to providing indirect evidence of an immediate
      source of this antioxidant in tears. Our hypothesis was that, if the source is
      corneal leakage, continuous tearing or rinsing of the eye will result in a marked
      decrease, by dilution, in ascorbate concentration in the reflex tears collected.
      Alternatively, the ascorbate concentration will be relatively constant if the
      main lacrimal gland secretion is the main immediate source. METHODS: Five
      successive samples of yawn-induced reflex tears were collected from the same eye
      of each of 42 subjects. In 36 of these volunteers, the testing eye was then
      flushed with 10 ml of saline and a sixth tear sample ('post-flush') was collected
      immediately. Tear ascorbate concentrations were measured using a validated high
      performance liquid chromatography method. RESULTS: The ascorbate concentration of
      the first sample (baseline) was slightly but significantly (P < 0.0001) lower
      (17.3 +/- 8.9 micro M) than the four subsequent samples in all subjects (average
      21.4 microM). Ascorbate concentrations of post-flush samples were very similar to
      pre-flush values. Mean +/- SD ascorbate concentrations of pre- and post-flush
      samples were, respectively, 22.5 +/- 10.9 and 17.3 +/- 5.8 microM. DISCUSSION:
      Results show that ascorbate is present in fresh reflex tears. Data do not support
      the view that the cornea is the source of tear ascorbate in healthy eyes. Rather,
      results indicate that ascorbate is present in main lacrimal gland secretion and
      that this antioxidant is depleted in basal tears. Measurement of tear ascorbate
      may offer useful information regarding antioxidant supply to and protection of
      the cornea.

PMID- 14720118
TI  - Circinate corneal scarring.
AB  - A 56-year-old man presented with symptoms of monocular diplopia and reduced
      vision in his left eye. Visual acuities were R6/6, L6/12. At his previous visit
      left visual acuity was 6/6. An irregular area of anterior corneal stromal
      scarring was evident, encroaching on the visual axis of the left eye. Rigid lens
      fitting improved left visual acuity to 6/6, however, lens wear caused a corneal
      abrasion over the lesion after one to two hours of wear. Several other contact
      lens and surgical strategies were employed to successfully address the visual
      requirements of the patient.

PMID- 14720119
TI  - Retained intraocular foreign body.
AB  - The presence of an intraocular foreign body following eye trauma may not be
      readily apparent. Serous complications may include, inter alia, endophthalmitis,
      cataract, retinal detachment and siderosis bulbi. We report an iron intraocular
      injury due to hammering 'metal on metal', which was diagnosed using ultrasonic
      biomicroscopy and successfully removed. Two months post-operatively, unaided
      vision was 6/6.

PMID- 14720120
TI  - Ian L Bailey.

PMID- 14720121
TI  - Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation
      to hepatic steatosis in patients with non-alcoholic fatty liver disease.
AB  - Hepatic steatosis is a major feature associated with NAFLD (non-alcoholic fatty
      liver disease). The aims of the present study were to assess the levels of PUFA
      (polyunsaturated fatty acids) in liver total lipids, triacylglycerols
      (triglycerides) and phospholipids of NAFLD patients in relation to those in
      adipose tissue and hepatic indexes related to oxidative stress as factors
      contributing to hepatic steatosis. Eleven control subjects and 19 patients with
      NAFLD were studied. Analysis of liver and abdominal adipose tissue fatty acids
      was carried out by GLC. The liver content of protein carbonyl groups and
      malondialdehyde were taken as indexes related to oxidative stress. NAFLD patients
      had a depletion in LCPUFA (long-chain PUFA) of the n -6 and n -3 series in liver
      triacylglycerols, with decreased 20:4, n -6/18:2, n -6 and (20:5, n -3+22:6, n 
      3)/18:3, n -3 ratios, whereas liver phospholipids contained higher n -6 and lower
      n -3 LCPUFA. These findings were accompanied by an enhancement of (i) n -6/ n -3
      ratio in liver and adipose tissue, (ii) 18:1, n -9 trans levels in adipose
      tissue, and (iii) hepatic lipid peroxidation and protein oxidation indexes. It is
      concluded that a marked enhancement in LCPUFA n -6/ n -3 ratio occurs in the
      liver of NAFLD patients, a condition that may favour lipid synthesis over
      oxidation and secretion, thereby leading to steatosis. Depletion of hepatic
      LCPUFA may result from both defective desaturation of PUFA, due to inadequate
      intake of precursors, such as 18:3, n -3, and higher intake of the 18:1, n -9
      trans isomer leading to desaturase inhibition, and from an increased peroxidation
      of LCPUFA due to oxidative stress.

PMID- 14720122
TI  - Characterization of iron binding in IscA, an ancient iron-sulphur cluster
      assembly protein.
AB  - Iron-sulphur clusters are one of the most common types of redox centre in
      biology. At least six proteins (IscS, IscU, IscA, HscB, HscA and ferredoxin) have
      been identified as being essential for the biogenesis of iron-sulphur proteins in
      bacteria. It has been shown that IscS is a cysteine desulphurase that provides
      sulphur for iron-sulphur clusters, and that IscU is a scaffold for the IscS
      mediated assembly of iron-sulphur clusters. The iron donor for iron-sulphur
      clusters, however, remains elusive. Here we show that IscA is an iron binding
      protein with an apparent iron association constant of 3.0x10(19) M(-1), and that
      iron-loaded IscA can provide iron for the assembly of transient iron-sulphur
      clusters in IscU in the presence of IscS and L-cysteine in vitro. The results
      suggest that IscA is capable of recruiting intracellular iron and delivering iron
      for iron-sulphur clusters in proteins.

PMID- 14720123
TI  - TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric
      carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated
      kinases) cascade activity dependent on c-Src activity.
AB  - Signalling by integrin-mediated cell anchorage to extracellular matrix proteins
      is co-operative with other receptor-mediated signalling pathways to regulate cell
      adhesion, spreading, proliferation, survival, migration, differentiation and gene
      expression. It was observed that an anchorage-independent gastric carcinoma cell
      line (SNU16) became adherent on TGF-beta1 (transforming growth factor beta1)
      treatment. To understand how a signal cross-talk between integrin and TGF-beta1
      pathways forms the basis for TGF-beta1 effects, cell adhesion and signalling
      activities were studied using an adherent subline (SNU16Ad, an adherent variant
      cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad
      cells, but not integrin alpha5-expressing SNU16 cells, showed an increase in
      adhesion on extracellular matrix proteins after TGF-beta1 treatment. This
      increase was shown to be mediated by an integrin alpha3 subunit, which was up
      regulated in adherent SNU16Ad cells and in TGF-beta1-treated SNU16 cells,
      compared with the parental SNU16 cells. After TGF-beta1 treatment of SNU16Ad
      cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP
      loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity
      were decreased, which showed a dependence on c-Src family kinase activity.
      Studies on adhesion and signalling activities using pharmacological inhibitors or
      by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity
      increased TGF-beta1-mediated cell adhesion slightly, but not the basal cell
      adhesion significantly, and that c-Src family kinase activity and decrease in
      Ras/ERKs cascade activity were required for the TGF-beta1 effects. Altogether,
      the present study indicates that TGF-beta1 treatment causes anchorage-independent
      gastric carcinoma cells to adhere by an increase in integrin alpha3 level and a c
      Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

PMID- 14720125
TI  - Proposal of Polish guidelines for conducting financial analysis and their
      comparison to existing guidance on budget impact in other countries.
AB  - BACKGROUND: Financial analysis (budget impact analysis, BIA) is increasingly
      required by decision-makers to ascertain the macroeconomic consequences of new
      product reimbursement in addition to proof of cost-effectiveness. Poland is in
      the process of drafting country-specific guidelines for BIA, positioned as
      complementary to economic evaluation in decision-making OBJECTIVES: The aim of
      this article is to present the Polish project and compare it with currently
      available guidance. METHODS: A checklist was developed that focuses on issues
      that are unique to BIA. An analysis of the differences between different national
      guidelines and their Polish counterparts was subsequently undertaken. RESULTS:
      The Polish project of BIA guidelines is composed of two sections. The first
      section presents the objective, the use of BIA, the responsibility for the
      preparation, and the target audience. The second section presents important
      methodological aspects that researchers should keep in mind when carrying out
      BIA. In comparison to existing guidance the Polish project appears to be more
      detailed. It includes more precise recommendations on perspective, time horizon,
      and reliability of data sources; reporting of results; rates of adoption of new
      therapies; and the probability of redeploying resources. CONCLUSIONS: Although
      there is an increased demand for BIA, there is only limited guidance on how such
      studies should be undertaken. It is hoped that the Polish guidelines can
      contribute to the development of such analyses and deliver benefit for Polish
      health-care decision-makers and beyond.

PMID- 14720124
TI  - A receptor-like kinase from Arabidopsis thaliana is a calmodulin-binding protein.
AB  - Screening a cDNA expression library with a radiolabelled calmodulin (CaM) probe
      led to the isolation of AtCaMRLK, a receptor-like kinase (RLK) of Arabidopsis
      thaliana. AtCaMRLK polypeptide sequence shows a modular organization consisting
      of the four distinctive domains characteristic of receptor kinases: an amino
      terminal signal sequence, a domain containing seven leucine-rich repeats, a
      single putative membrane-spanning segment and a protein kinase domain. Using
      truncated versions of the protein and a synthetic peptide, we demonstrated that a
      region of 23 amino acids, located near the kinase domain of AtCaMRLK, binds CaM
      in a calcium-dependent manner. Real-time binding experiments showed that AtCaMRLK
      interacted in vitro with AtCaM1, a canonical CaM, but not with AtCaM8, a
      divergent isoform of the Ca2+ sensor. The bacterially expressed kinase domain of
      the protein was able to autophosphorylate and to phosphorylate the myelin basic
      protein, using Mn2+ preferentially to Mg2+ as an ion activator. Site-directed
      mutagenesis of the conserved lysine residue (Lys423) to alanine, in the kinase
      subdomain II, resulted in a complete loss of kinase activity. CaM had no
      influence on the autophosphorylation activity of AtCaMRLK. AtCaMRLK was expressed
      in reproductive and vegetative tissues of A. thaliana, except in leaves.
      Disruption in the AtCaMRLK coding sequence by insertion of a DsG transposable
      element in an Arabidopsis mutant did not generate a discernible phenotype. The
      CaM-binding motif of AtCaMRLK was found to be conserved in several other members
      of the plant RLK family, suggesting a role for Ca2+/CaM in the regulation of RLK
      mediated pathways.

PMID- 14720126
TI  - Outcomes research in health care: simulations to drive cost conclusions.

PMID- 14720127
TI  - Modeling the efficiency of reaching a target intermediate end point: a case study
      in type 2 diabetes in the United States.
AB  - OBJECTIVE: The objective of this study was to describe an approach to modeling
      the efficiency of an intervention by focusing on an established intermediate end
      point directly. A case study addresses the economic efficiency of obtaining dual
      glycemic control over time, according to initial choice of treatment. METHODS:
      From the perspective of a payer in the United States, instead of the usual
      approach of basing the model on projecting long-term diabetic complications from
      glycemic control, this model focuses directly on glycemic control. Treatment
      changes and associated health-care utilization needed to address postprandial
      glucose. After assigning each of 10000 drug-naive patients, HbA1c, age, race, and
      sex based on distributions from a randomized clinical trial, the model applies
      the efficacy of nateglinide compared to metformin. Sensitivity analyses were
      carried out for all parameters. Costs are reported in year 2000 US dollars and
      discounted at 3%. RESULTS: In the base case, starting on nateglinide and
      increasing the time in dual glycemic control over 3 years by 2.4 months led to
      savings of US dollars 295 compared to starting on metformin. Savings increased
      with stricter treatment criteria but decreased if glycemic control was better
      initially. CONCLUSIONS: This study illustrates the use of an efficiency model
      that focuses directly on the relevant short-term end point: glycemic control.
      Starting patients with nateglinide is shown to be an efficient way of obtaining
      dual glycemic control during the first 3 years of treatment.

PMID- 14720128
TI  - The impact of olanzapine, risperidone, or haloperidol on the cost of
      schizophrenia care in a medicaid population.
AB  - OBJECTIVE: The objective of this study was to assess the impact of medication
      treatment on Medicaid costs for persons with schizophrenia. METHODS: Michigan
      Medicaid claims from January 1995 through September 1998 were analyzed for
      persons with schizophrenia diagnoses who initiated olanzapine (n = 458),
      risperidone (n = 481), or haloperidol (n = 252) treatment between January 1996
      and September 1997. Total and component Medicaid payments were compared for the
      year after treatment initiation, with simultaneous adjustment for patient
      demographics, comorbid conditions, prior medication use, prior service use, and
      prior year costs. RESULTS: Significant baseline differences existed between the
      groups in prior medication and service use. Adherence to index medication varied
      between the groups (O = 60%; R = 54%; H = 37%; P < =.01 for each pairwise
      comparison). Average postperiod costs were US dollars 14512 per subject. After
      baseline adjustment, there were no significant differences in mean total cost.
      Excluding index medication costs, the olanzapine group's average cost was
      significantly lower than risperidone (-US dollars 1791, P =.002) and haloperidol
      (-US dollars 2080, P =.003), whereas the risperidone and haloperidol groups were
      not significantly different. The differences were driven by significantly lower
      cost for inpatient services for other medications among the olanzapine group.
      CONCLUSION: Total costs of schizophrenia care associated with olanzapine,
      risperidone, or haloperidol were similar, but component costs differed. Relative
      to risperidone or haloperidol, olanzapine may have a higher acquisition cost, but
      may decrease inpatient costs and be associated with more optimal medication use
      patterns. Use of risperidone may also increase pharmacy costs and be associated
      with greater persistence, relative to haloperidol.

PMID- 14720129
TI  - A pharmacoeconomic evaluation of seven-valent pneumococcal conjugate vaccine in
      Spain.
AB  - BACKGROUND: Streptococcus pneumoniae is a leading cause of illness in children.
      Seven-valent pneumococcal conjugate vaccine (PCV-7), recently approved in the
      United States, is the first vaccine to provide protective immunity against
      pneumococcal disease in children under the age of 2. PCV-7 is nearly 100%
      effective in preventing invasive pneumococcal infections and has been shown to
      significantly decrease the incidence of pneumonia and otitis media. OBJECTIVE:
      The objective of this study was to evaluate the health outcomes, costs, and cost
      effectiveness of vaccination with PCV-7, compared with no vaccination for
      children in Spain. METHODS: A health state model was used to determine the health
      and economic outcomes in vaccinated and unvaccinated groups among children less
      than 5 years old. This analysis was conducted for a 10-year time horizon,
      beginning with initial vaccinations. Information on the burden of pneumococcal
      disease, in terms of data on the incidence and seroprevalence of disease, was
      collected from published and unpublished records, supplemented, and verified by
      Spanish pediatric and infectious disease experts. The efficacy of PCV-7 was based
      on updated findings of the Kaiser Permanente Efficacy Study. A cost-of-illness
      estimate for each pneumococcal disease was determined using decision tree
      analysis that considered direct and indirect costs. A birth cohort analysis
      compared the expected cost of vaccinated populations to age-matched unvaccinated
      populations. RESULTS: Implementing a PCV-7 vaccine program in Spain in a birth
      cohort of 360000 is expected to save approximately 16 lives and 132000 cases of
      pneumococcal disease over 10 years, resulting in total savings estimated at Euros
      81 million (ESP13.5 billion), of which Euros 43.5 million (ESP7.1 billion) are
      direct medical savings. At a vaccine cost up to Euros 56.87 per dose (ESP9,462,
      the total cost of vaccinating a birth cohort of 360000 will be offset by the
      total savings owing to reduced morbidity. CONCLUSIONS: Implementing a universal
      PCV-7 vaccination program in Spain will significantly decrease the mortality and
      morbidity associated with pneumococcal infections in young children. At an
      assumed cost of Euros 48.56 (ESP8080) per dose, PCV-7 vaccination of Spanish
      children under the age of 5, followed over a 10-year period, is cost saving from
      the societal perspective and cost-effective from the payer perspective at Euros
      22500 per LYG (ESP3,734713), comparing favorably with other preventive programs
      in Spain.

PMID- 14720130
TI  - Using clopidogrel in non-ST-segment elevation acute coronary syndrome patients: a
      cost-utility analysis in Spain.
AB  - OBJECTIVE: The objective of this study was to estimate the cost-effectiveness of
      clopidogrel, administered for 1 year after hospital admission for non-ST-segment
      elevation acute coronary syndrome in the Spanish public health network. METHODS:
      A cost-utility analysis was conducted from the societal perspective. A Markov
      decision tree was constructed for modeling the long-term cardiovascular events
      according to the probabilities of the CURE study, the Framingham study, and the
      Spanish age-sex-specific mortality rates. The costs of the therapy were
      calculated mainly using the cost per diagnosis-related group in the Spanish
      National Health System. The utilities of the various states were estimated using
      data from published studies. A 3% discount rate was used for both the costs and
      the utilities. An expected value sensitivity analysis and a Monte Carlo
      microsimulation probabilistic analysis were performed. RESULTS: The cost per
      quality-adjusted life-year (QALY) saved owing to clopidogrel in the base case was
      about Euros 12000. This expected cost-effectiveness ratio was very sensitive to
      the age of the patient, the base risk of cardiovascular events, and the precision
      of the estimated effectiveness of clopidogrel. The cost per QALY ranged between
      some Euros 5000 for a high-risk, 40-year-old patient and Euros 30000 for a low
      risk, 80-year-old patient. According to the accepted threshold for Spanish
      society, the probability that clopidogrel was cost-effective in the base analysis
      case was 85.3%. CONCLUSIONS: By Spanish standards, the use of clopidogrel in
      patients with non-ST-segment elevation acute coronary syndrome is cost-effective,
      at least when used for patients at high risk of presenting cardiovascular events.

PMID- 14720131
TI  - Relationships of clinical, psychologic, and individual factors with the
      functional status of neck pain patients.
AB  - OBJECTIVE: The objective of this study was to use both generic and disease
      specific functional measures examining relationships of clinical, psychologic,
      and individual factors with the functional status of neck pain patients. METHODS:
      Patients who visited a university-based spine clinic and reported neck pain were
      included in this study. A comprehensive computerized survey questionnaire was
      used to collect the information related to this study. The questionnaire also
      contained a generic measure, short form 12-item survey (SF-12), and a disease
      specific measure, neck disability index (NDI). Correlation and multiple
      regression analysis were conducted to examine the relationships. RESULTS: A range
      of clinical, psychologic, and individual factors emerged to be significant
      predictors of the NDI or physical component of the SF-12 (PCS). The predictors of
      higher NDI included higher levels of neck pain, higher levels of back pain,
      higher levels of pain in arm or shoulder areas, not working, lower education,
      higher stress, the presence of depression or anxiety, and smoking. The predictors
      of lower PCS included not working, higher levels of back pain, higher levels of
      neck pain, lower education, female sex, the presence of cardiovascular disorders,
      the absence of cervical disk disorders, and older age. CONCLUSIONS: The
      predictors of the NDI or PCS appear to be multidimensional. Interventions
      designed to maximally improve the functional status of neck pain patients should
      be multifaceted and involve multidisciplinary teams. Selection of the most
      appropriate functional measures for an intervention study should consider
      differences between the generic and disease-specific measures in terms of their
      respective relationships with targeted factors. Prospective studies are needed to
      confirm the relationships observed in this study.

PMID- 14720132
TI  - Cost-effectiveness versus cost-utility analysis of interventions for cancer: does
      adjusting for health-related quality of life really matter?
AB  - OBJECTIVE: The US Public Health Service Panel on Cost-Effectiveness has
      recommended the use of quality-adjusted life-years (QALYs) as the best way to
      estimate outcomes in a cost-effectiveness analysis. We evaluate the importance of
      this recommendation by assessing whether adjusting for health-related quality of
      life affects the ultimate resource allocation decision implied by the cost
      effectiveness ratio for interventions aimed at cancer prevention and control.
      METHODS: We identified 110 interventions in 39 articles for which both cost/life
      year and cost/QALY were reported. Interventions were forms of prevention, early
      detection, or treatment of cancer. We calculated a Spearman correlation to assess
      the ordinal relationship between cost/life-year and cost/QALY. In addition, we
      employed various decision thresholds to assess whether the use of cost/life-year
      would yield different resource allocation decisions than the use of cost/QALY.
      RESULTS: The correlation between cost/life-year and cost/QALY is 0.96 (P <.0001).
      Assuming a US dollars 50000 decision threshold, adjustment for quality of life
      would affect the implied choice in 5% of cases. With a US dollars 400000
      threshold, adjustment for quality of life would affect choice for 2% of
      interventions. CONCLUSIONS: For interventions aimed at cancer, the outcome
      measures of cost/life-year and cost/QALY are highly correlated with one another.
      Although adjusting for quality of life can make an important difference in the
      evaluation of alternative approaches to cancer prevention and control, it often
      does not.

PMID- 14720133
TI  - Assessment of health-related quality of life in children: a review of conceptual,
      methodological, and regulatory issues.
AB  - Recently, the FDA has encouraged testing of medications among pediatric patients
      during drug development. Pharmaceutical companies have responded by conducting
      more clinical trials among children, and researchers are becoming aware of the
      unique challenges of assessing pediatric health outcomes, including health
      related quality of life (HRQL). Like adults, children experience effects of
      illness and treatment beyond physiologic outcomes. Further pediatric HRQL
      research is necessary to examine these broader psychosocial outcomes and provide
      a thorough understanding of the effects of treatment on children's health status.
      The purpose of the current review is to discuss key regulatory and methodologic
      developments and provide guidance for future research on pediatric HRQL. This
      review of pediatric HRQL assessment includes five sections: 1). recent pediatric
      regulatory developments in the United States; 2). issues in defining and
      conceptualizing pediatric HRQL, including the importance of contextual variables
      such as family and peer systems; 3). methodologic issues (e.g., the proxy
      question, developmental differences, response sets) with recommendations for
      addressing these issues in clinical trials; 4). validated generic and condition
      specific pediatric HRQL measures; and 5). a recommendation for additional
      research on the HRQL impact of childhood psychiatric disorders. It is advocated
      that assessment of HRQL among children should be conducted regularly as an
      integral part of drug development.

PMID- 14720134
TI  - A comprehensive strategy for the interpretation of quality-of-life data based on
      existing methods.
AB  - OBJECTIVES: Health-related quality of life (HRQL) instruments generally undergo a
      rigorous development and validation process. In contrast, methods for
      interpreting HRQL data are varied, and no comprehensive widely applicable
      procedure exists. Determining whether differences are statistically significant
      is the most common method, but this yields conclusions that may be difficult to
      understand in a clinical context or which may be of no practical value.
      Consequently, there is a need for a comprehensive interpretation strategy that
      gives results that are meaningful to a variety of audiences, including patients,
      clinicians, and decision-makers. METHODS: The review of available interpretation
      strategies revealed that not all methods are applicable to all questionnaires,
      and some strategies may be difficult to implement for interpreting trial results.
      In addition, the issues decision-makers may have when assessing HRQL results have
      not really been addressed: what is measured and what is the meaning beyond
      statistical significance? RESULTS: A comprehensive stepwise strategy, based on
      the most effective methods available, has been developed to address the key
      interpretation issues of decision-makers. It is structured around several steps:
      understanding the content of the questionnaire; evaluating the magnitude of
      changes and their statistical significance; determining whether results are
      clinically significant, e.g., whether the observed changes crossed ranges of
      established threshold for meaningful differences; comparing pre- and post
      treatment scores distribution with norms of references; and relating score
      changes to other outcomes end points such as morbidity, death, compliance,
      resource utilization, or productivity. CONCLUSIONS: The proposed strategy should
      help to structure and successfully address interpretation issues and thus make
      HRQL results more convincing.

PMID- 14720135
TI  - ISPOR education steering committee: to provide insight into the characteristics
      and components of the PE/OR fellowship programs.

PMID- 14720136
TI  - Effect of morpholino antisense oligonucleotide against lumican mRNA in human
      embryonic kidney (HEK) 293 cells.
AB  - Lumican is a member of the small-leucine-rich proteoglycan (SLRP) family and is
      overexpressed during wound healing of the cornea, in ischemic and reperfused
      heart, and in several cancer tissues. Lumican is considered to regulate the
      collagen fibril diameter and interfibrillar spacing. However, the effect of
      lumican on cell growth has not been adequately examined. In the present study, we
      attempted to clarify whether lumican contributes to human embryonic kidney (HEK)
      293 cell growth, using the morpholino antisense oligonucleotide (m-anti oligo)
      against lumican mRNA. M-anti oligo is a novel oligonucleotide and exhibits a
      higher antisense activity, higher water solubility, and greater resistance to
      nucleases in target cells than phosphorothioate types of oligonucleotide. After
      delivery of m-anti oligo against lumican mRNA, the fluorescein 5-isothiocyanate
      (FITC) conjugated oligonucleotides were observed in the cytoplasm and nucleus of
      HEK 293 cells at 24 h by confocal laser microscopy. M-anti oligo for lumican mRNA
      strongly inhibited the synthesis of lumican protein in the HEK 293 cells, and the
      HEK cell growth rate was higher than those in the control groups. These findings
      may indicate that lumican protein has an inhibitory effect on HEK 293 cell growth
      in vitro.

PMID- 14720137
TI  - Immunohistochemical analysis of centromere protein F expression in buccal and
      gingival squamous cell carcinoma.
AB  - Centromere protein F (CENP-F) expression (localization and characteristics) in
      relation to tumor clinicopathological parameters was immunohistochemically
      examined and evaluated in 47 archival biopsy specimens of buccal and gingival
      squamous cell carcinomas (SCC). Centromere protein F expression was detected in
      79% of the samples. An increase in the labeling index (LI) with WHO grading was
      obtained (P < 0.05). Correlations were obtained between the CENP-F LI and tumor
      size (P < 0.05). Immunoelectron microscopy showed CENP-F nuclear staining as
      punctate or fine dots. The present study shows that CENP-F expression and
      detection of a more specific cell subpopulation presents a theoretical advantage
      for the analysis of the precise cell cycle of G2 to M cells, compared to Ki-67.

PMID- 14720138
TI  - Invasive micropapillary carcinoma of the breast: clinicopathological and
      immunohistochemical study.
AB  - Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique
      variant of invasive ductal carcinoma, but its biological behavior has not been
      elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The
      incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade
      (75.0%), as well as poorly differentiated histological grade (81.3%), was
      frequently seen. Lymph node metastases were evident in 92.9% of the examined
      cases, and about half of them showed more than 10 positive nodes. Comparison
      between serially experienced invasive ductal carcinoma, not otherwise specified
      (IDC-NOS), revealed that both high nuclear grade and poor histological grade were
      significantly more frequent (P < 0001), there was a lower frequency of positive
      estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency
      of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P <
      0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show
      any statistically significant differences in frequency for positive p53, matrix
      metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or
      E-cadherin. However, IMPCa showed a significantly increased number of blood
      vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa
      is, at least, the same or more aggressive than lymph node positive cases of IDC
      NOS. Hence, not only the high incidence of lymph node metastases but also
      distant, blood-borne metastases may be important.

PMID- 14720139
TI  - Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a
      laryngeal tumor.
AB  - Intraoral localization of neuroendocrine carcinoma, usually called Merkel cell
      carcinoma, is extremely rare. A case of neuroendocrine carcinoma that was a
      counterpart of laryngeal neuroendocrine carcinoma but was not a Merkel cell
      carcinoma, occurring at the mandibular gingiva in a 69-year-old Japanese man, is
      described. The tumor formed a cauliflower-like mass, measuring 20 x 20 mm, with a
      small area of necrosis. A computed tomography image showed metastasis in the
      right submandibular lymph node. Histopathologically, the tumor was composed of
      immature, small round cells that formed anastomosing trabecular nests. Few
      mitotic and no necrotic features were observed in the nests. Immunohistochemical
      studies showed positive staining for chromogranin, synaptophysin and neuron
      specific enolase in the tumor nests. We diagnosed it as an atypical carcinoid
      (neuroendocrine carcinoma), a counterpart to the same type of tumor occurring in
      the larynx. The present case is an extremely rare case of neuroendocrine
      carcinoma without the feature of Merkel cell carcinoma arising from the gingiva.

PMID- 14720140
TI  - Rhinoscleroma associated with Rosai-Dorfman reaction of regional lymph nodes.
AB  - Rhinoscleroma is an uncommon chronic, destructive infection of the respiratory
      mucosa caused by Klebsiella rhinoscleromatis. This coccobacillus can be found in
      the typical histiocytes, the Mikulicz cells. Extranasal and nodal involvement in
      this disease is rare, but documented. Rosai-Dorfman disease or sinus
      histiocytosis with massive lymphadenopathy is also a rare, non-hereditary
      disorder. Bilateral cervical lymphadenopathy with emperipolesis, as the main
      histological characteristic, is the most common presentation. It can also occur
      extranodally. We report a case of rhinoscleroma occurring in a 62-year-old woman
      since 1984, who developed parotid gland and lymph node involvement. The changes
      in the nasal mucosa and the parotid gland showed chronic inflammation with
      Mikulicz cells. In the lymph nodes, features characteristic of Rosai-Dorfman
      disease were seen. Taking into consideration the literature dealing with both of
      these diseases, we discuss that Rosai-Dorfman disease could be a special type of
      lymph node reaction and is not necessarily an entity of its own. Therefore, it
      should be known as Rosai-Dorfman lymph node reaction. Furthermore, there seems to
      be an interconnection between Rosai-Dorfman disease and rhinoscleroma.

PMID- 14720141
TI  - Composite type of breast carcinoma with endocrine differentiation: a cytological
      and immunohistochemical study.
AB  - We describe a case of breast carcinoma with endocrine differentiation containing
      a mixture of three different histological features that occurred in a 71-year-old
      woman. Histologically, the tumor was predominantly intraductal, but slightly
      invasive. In the intraductal lesion, the tumor consisted mainly of ovoid to round
      cells with a modest to abundant amount of granular eosinophilic cytoplasm or
      intracytoplasmic mucin (mucin-producing carcinoma in situ). It also consisted, in
      part, of plump spindle cells with scant cytoplasm that contained argyrophilic
      granules in a trabecular pattern or an arrangement of perivascular pseudorosettes
      (atypical carcinoid tumor like-features). Mucous lake and tumor cells floating in
      mucin were seen in the invasive lesion (mucinous carcinoma). Immunohistochemical
      staining revealed endocrine differentiation of the tumor cells of both
      intraductal and invasive lesions. These findings suggest that the different
      histological features derived from pluripotent cells upon endocrine
      differentiation, and that endocrine differentiation of the tumor cells had
      already occurred at an earlier stage of carcinogenesis, prior to the appearance
      of the mucinous carcinoma. Cytologically, plasmacytoid tumor cells appeared in
      loosely cohesive clusters or as sparsely single cells in a background of a
      mucinous substance.

PMID- 14720142
TI  - Disseminated malignant solitary fibrous tumor of the pleura.
AB  - Solitary fibrous tumor (SFT) of the pleura typically forms a localized pleura
      based mass, and most are benign. A rare case of disseminated malignant SFT of the
      pleura is reported. The patient was a 71-year-old man who presented with
      complaints of shortness of breath to his primary care physician. A diagnosis of
      malignant mesothelioma was suspected, based on clinical, radiological and needle
      biopsy findings. He was referred to our institution for surgery. An extrapleural
      pneumonectomy, encompassing all pleural masses, was performed. Gross examination
      of the resected specimen was remarkable for numerous masses, ranging in size from
      0.2 to 13.5 cm, covering the majority of the visceral pleura. Histologically, the
      tumor was composed of short spindle cells admixed with variable proportions of
      collagenous stroma. There were great intra- and intertumoral heterogeneity in
      tumor growth pattern, cellularity, pleomorphism and mitoses. Histologically
      malignant areas were present in all of the masses examined. The neoplastic cells
      were diffusely and intensely positive for bcl-2. Most tumor cells were also
      strongly stained for CD34 and CD99. Staining for cytokeratin was negative. The
      tumor also revealed p53 over-expression. Thus, the histological and
      immunohistochemical features of the tumor were consistent with a disseminated
      malignant SFT. This report shows that SFT rarely presents with disseminated
      pleural involvement, and a panel with CD34, bcl-2 and cytokeratin are valuable
      for differentiating SFT from malignant mesothelioma and other malignant spindle
      cell neoplasms of the pleura.

PMID- 14720143
TI  - Intraductal oncocytic papillary neoplasm of the liver.
AB  - A very rare case of intraductal oncocytic papillary carcinoma of the liver is
      reported. A 63-year-old Japanese man was admitted to our clinic because of
      abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic
      neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe.
      Combined percutaneous and endoscopic retrograde cholangiographies revealed the
      unilocular cystic neoplasm contained a lot of mucus and communicated with the
      left segmental intrahepatic bile duct, and that mucus filled the left segmental
      and hepatic ducts. Left lobectomy was performed. The postoperative course was
      good, and the patient is free of disease 30 months after operation. Pathological
      examination revealed that the cavity of the neoplasm was continuous with the left
      segmental intrahepatic bile duct, and that a lot of mucus was present in the
      neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm
      consisted of papillary growth of atypical epithelial cells with oncocytic
      changes. Atypical goblet cells were also recognized. No invasion into the
      surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion
      occasionally showed epithelial dysplasia and contained a lot of mucus.
      Immunohistochemically, the tumor cells were rich in mitochondria and were
      immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and
      hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic
      alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous
      mitochondria and mucus droplets. Intraductal neoplasm communicating with the
      intrahepatic bile ducts has rarely been reported. The present case suggests that
      intraductal oncocytic papillary neoplasm, as described in the pancreas, may also
      occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm
      may express hepatocellular and pancreatic acinar phenotypes.

PMID- 14720144
TI  - Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen.
AB  - A case of so-called inflammatory pseudotumor (IPT), occurring in the spleen of a
      77-year-old woman, is reported. The spleen contained a well-circumscribed mass
      with central hemorrhage and necrosis. Histologically, spindle cells were
      dispersed in a background of abundant inflammatory cells, predominantly
      lymphocytes and plasma cells. The cells possessed enlarged, sometimes twisted or
      irregularly folded, nuclei that contained vesicular chromatin, and small but
      distinct, centrally located nucleoli. Immunohistochemically, the spindle cells
      were diffusely positive for vimentin, and focally positive for follicular
      dendritic cell (FDC) markers (Ber-MAC-DRC for CD35 and CNA.42). The Epstein-Barr
      virus (EBV) was exclusively detected in the spindle cells by in situ
      hybridization analysis. The cells also expressed the latent membrane protein-1
      (LMP-1) of EBV, and polymerase chain reaction (PCR) analysis revealed that the
      LMP-1 gene had a 30-bp deletion and three point mutations, although their
      significance remains controversial. Inflammatory pseudotumor is a descriptive
      term that encompasses several different entities, and recent investigations have
      revealed the existence of neoplastic entities among IPT. One of the neoplastic
      IPT, recently designated 'IPT-like FDC tumor', is characterized by proliferation
      of EBV-positive FDC and commonly occurs in the liver and spleen. Because such
      tumors are capable of recurrence and metastasis, it is important to consider the
      possibility of an IPT-like FDC tumor when making a diagnosis of a hepatic/splenic
      IPT-like lesion.

PMID- 14720145
TI  - Retroperitoneal mucinous cystadenoma: report of two cases and review of the
      literature.
AB  - Primary retroperitoneal cystic tumor is extremely rare, and its histogenesis and
      biological behavior remain speculative. Two surgical cases of retroperitoneal
      mucinous cystadenoma (Case 1, an 18-year-old woman; and Case 2, an 85-year-old
      woman) are reported. The cystadenomas in these cases were mainly lined by a
      monolayer of columnar or thin flat cells. Case 1 was positive for mucin and
      epithelial membrane antigen, whereas Case 2 was positive for a mesothelial marker
      (calretinin). Ciliated epithelium was also interspersed in Case 2. Some parts
      showed papillary projections, resembling well-differentiated papillary
      mesothelioma. Within the cyst walls of both cases, ovarian-like stroma that was
      positive for both estrogen and progesterone receptors was found. Interestingly,
      focal nodular hyperplasia of the liver was also detected in Case 1. We believe
      the retroperitoneal mucinous cystadenoma might have arisen from the peritoneum
      via mucinous epithelial metaplasia with a phenotype of extragenital Mullerian
      system.

PMID- 14720146
TI  - Adenocarcinoma arising from mature cystic teratoma of the ovary.
AB  - An extremely rare adenocarcinoma arising from a mature cystic teratoma is
      reported. A 58-year-old woman underwent bilateral salpingo-oophorectomy because
      of a tumor in each ovary. The right ovarian tumor (solid, 9.6 x 9.6 x 6.3 cm) was
      a benign thecoma. Histology revealed the left ovarian cystic tumor (multilocular,
      6.4 x 4.8 x 2.8 cm) was a mature cystic teratoma containing skin, fatty tissue
      and respiratory epithelial tissue. In addition, there was a small focal
      adenocarcinomatous lesion contiguous to the teratomatous ciliated columnar
      epithelium without stromal invasion (so-called adenocarcinoma in situ) that was
      suggestive of respiratory epithelium origin. However, goblet cells were present
      in the glandular structures of the lesion and immunohistochemical staining was
      segmentally strongly positive for CK20 and uniformly negative for CK7. These
      results suggested that the adenocarcinomatous lesion had a mucin secretory
      gastrointestinal phenotype. Further investigation and the collection of more
      cases is necessary to determine the origin and growth mechanism of adenocarcinoma
      arising from mature cystic teratoma of the ovary.

PMID- 14720147
TI  - Personal security: Clinical applications of the wearable defibrillator.

PMID- 14720148
TI  - Use of a wearable defibrillator in terminating tachyarrhythmias in patients at
      high risk for sudden death: results of the WEARIT/BIROAD.
AB  - The automatic ICD improves survival in patients with a history of sudden cardiac
      arrest. However, some patients do not meet the guidelines for ICD implantation or
      are unable to receive an implantable device. This study tested the hypothesis
      that these patients could benefit from a wearable cardioverter defibrillator.
      Patients with symptomatic heart failure and an ejection fraction of <0.30 (WEARIT
      Study) or patients having complications associated with high risk for sudden
      death after a myocardial infarction or bypass surgery not receiving an ICD for up
      to 4 months (BIROAD Study) were enrolled into two studies. After a total of 289
      patients had been enrolled in the trial (177 in WEARIT and 112 in BIROAD),
      prespecified safety and effectiveness guidelines had been met. Six (75%) of eight
      defibrillation attempts were successful. Six inappropriate shock episodes
      occurred during 901 months of patient use (0.67% unnecessary shocks per month of
      use). Twelve deaths occurred during the study 6 sudden deaths: 5 not wearing and
      1 incorrectly wearing the device). Most patients tolerated the device although 68
      patients quit due to comfort issues or adverse reactions. The results of the
      present study suggest that a wearable defibrillator is beneficial in detecting
      and effectively treating ventricular tachyarrhythmias in patients at high risk
      for sudden death who are not clear candidates for an ICD and may be useful as a
      bridge to transplantation or ICD in some patients.

PMID- 14720149
TI  - Atrial refractoriness and action potential duration after sudden reversal of
      atrioventricular sequence.
AB  - To address the potential of atrioventricular (AV) asynchrony to provoke cardiac
      arrhythmias, atrial electrophysiology was examined during normal and reversed AV
      interval in anesthetized pigs. A new automatic stimulation technique was adapted
      to monitor rapid changes in the effective refractory period (ERP), using
      continuous AV sequential pacing, incremental extrastimulus interval scanning, and
      automatic detection of capture. Right atrial ERP using 2-8 ms stimulus interval
      increments and right atrial and ventricular monophasic action potential (MAP)
      duration were determined simultaneously when the AV interval was changed from
      normal (+80 ms) to reversed (-40 ms) and back. During reversed AV interval the
      peak right atrial pressure increased from 8 +/- 3 to 14 +/- 4 mmHg (P < 0.001)
      and mean arterial pressure decreased from 86 +/- 18 to 65 +/- 21 mmHg (P <
      0.001). At new steady state, atrial ERP and MAP duration at 90% level of
      repolarization were lengthened by 22 +/- 16 and 42 +/- 12 ms respectively (P <
      0.001). Ventricular MAP duration did not change. A statistically significant
      lengthening in atrial ERP could be demonstrated in 5-10 seconds. After reversion
      of the AV sequence, the ratio of atrial ERP to MAP duration decreased from 1.27
      to 0.94 (P < 0.001) on average for 15 seconds, the change being thought to favor
      reentry. Thus atrial wall stress from contraction during ventricular systole even
      for a short period of time modifies atrial electrophysiology. Deficient AV
      synchrony may immediately contribute to the development of atrial arrhythmias.

PMID- 14720150
TI  - Optimal pacing for symptomatic AV block: a comparison of VDD and DDD pacing.
AB  - VDD pacing provides the physiological benefits of atrioventricular synchronous
      pacing with the convenience of a single lead system, but is hampered by
      uncertainty regarding long term atrial sensing and potential development of sinus
      node disease. To examine the long-term reliability and complication rates of VDD
      pacing, we compared the outcome of 112 consecutive patients (age 70 +/- 13 years,
      59% men) with symptomatic AV block who received a single pass bipolar VDD system,
      to 80 patients (age 63 +/- 16 years, 70% men) who received DDD pacing for the
      same indication. All patients were judged to have intact sinus node function
      based on submitted ECGs and monitoring results at the time of implant. Implant
      time was reduced in VDD patients compared to DDD patients (63 +/- 20 vs 97 +/- 36
      minutes, P < 0.0001). Implant complications occurred in 5 (6%) DDD patients
      compared to 3 (3%) VDD patients (P = 0.15). The implant P wave was lower with VDD
      pacing compared to DDD patients (2.91 +/- 1.48 vs 4.0 +/- 1.7 mv, P < 0.0001),
      but remained stable during long-term follow-up in both groups. During 17.7 +/-
      10.0 months of follow-up in the VDD group, only two VDD patients were
      reprogrammed to VVIR mode, compared to three DDD patients. Physiological
      atrioventricular activation was maintained in 94%-99% of beats throughout the
      follow-up period in the VDD group. VDD pacing is an excellent strategy for
      treatment of patients with symptomatic AV block. The lower cost, high
      reliability, and abbreviated implantation time suggest that VDD pacing is a
      viable alternative to DDD pacing in patients with high degree AV block and normal
      sinus node function.

PMID- 14720151
TI  - Effect of autonomic stressors on rate control in pacemakers using ventricular
      impedance signal.
AB  - The aim of this study is to evaluate the heart rate adaptation obtained by a
      pacemaker, based on a measure of ventricular impedance in patients undergoing
      autonomic challenges. The evaluation procedure was based on the analysis of the
      mean value (MV) and heart rate variability (HRV) of RR and systolic pressure
      intervals, according to a set of neurovegetative stressors (controlled
      respiration in supine position and during active standing; mental stress;
      handgrip, and noninvasive sinusoidal stimulation of carotid baroreceptors). Each
      test lasted 5 minutes. Fifteen chronotropic incompetent patients first implanted,
      were studied three months after implantation. ECG, respiration activity, and
      noninvasive blood pressure were monitored. HRV was evaluated by spectral
      analysis. Variability in the low frequency (LF) and high frequency (HF) bands was
      compared by computing percentage and absolute powers. We found that baseline HR
      was 72.2 +/- 5.5 beats/min, in mental stress was 76.8 +/- 7.8 beats/min, in
      handgrip was 79.2 +/- 6.3 beats/min, and in active standing was 80.9 +/- 8.6
      beats/min (P < 0.01, Friedman's test). During active standing, LF component was
      significantly higher with respect to baseline (25.7% of total power in standing;
      9.4% in baseline, P < 0.01) and it was synchronous to the LF component of the
      arterial pressure variability. Carotid activation/deactivation by neck suction
      induced synchronous changes in the paced rates. In conclusion, closed loop
      strategy based on ventricular contractility continuously controls heart rate by
      tracking the sympathetic modulation to the heart.

PMID- 14720152
TI  - Parasympathetic blockade promotes recovery from atrial electrical remodeling
      induced by short-term rapid atrial pacing.
AB  - The purpose of the present study was to assess the influence of autonomic
      blockade on shortening of effective refractory period (ERP) induced by short-term
      rapid atrial pacing (RAP) and its recovery process. Fifteen patients (8 men, 7
      women, age 52 +/- 16 years) without structural heart disease and without a
      history of atrial fibrillation were included in this study. All patients
      underwent RAP at a cycle length of 300 ms for 5 minutes, after which the ERP was
      measured in all patients at 1, 3, 5, 7.5, and 10 minutes following cessation of
      RAP. In ten patients, these RAP and measurements of ERPs were repeated after
      administration of propranolol (P) and subsequent administration of atropine (P +
      A), respectively. In the remaining five patients atropine (A) was given first and
      then the administration of propranolol followed (P + A). Relative to the baseline
      value, the ERP immediately after RAP did not differ significantly from the
      Control(C), P, A, or P + A (C, 79%+/- 8%; P, 82%+/- 9%; A, 80%+/- 6%; P + A,
      82%+/- 13%). However, the ERP 3 minutes after cessation of RAP was significantly
      (P < 0.05) longer in A (93%+/- 4%) and P + A (97%+/- 5%) than that in C (86%+/-
      5%) and P (86%+/- 5%). The recovery time for ERP to return to pre-RAP value was
      significantly shorter during A and P + A than during either C or P (C, 536 +/-
      161 s; P, 503 +/- 172 s; A, 282 +/- 111 s; P + A, 291 +/- 147 s; P < 0.05).
      Parasympathetic blockade may promote recovery from ERP shortening induced by
      short-term RAP.

PMID- 14720153
TI  - Influence of high-pass filtering on noncontact mapping and ablation of atrial
      tachycardias.
AB  - The aim of the study was to define the impact of different high-pass filter
      settings (HPF) on the accuracy of mapping of ectopic atrial tachycardias (EAT)
      using a noncontact mapping (NCM) system. In 20 patients with 22 EAT a noncontact
      probe was deployed in the right (n = 19) or in the left atrium (n = 3). The
      device enables interpolation and analysis of unipolar electrograms. It provides
      information on focus localization and signal morphology. These parameters were
      compared in different HPF of 0.5 Hz, 2 Hz, 8 Hz, and 16 Hz. The NCM signal
      morphology was preserved at all HPF. An initial negative deflection recorded by
      NCM system showed a positive predictive value of 93% regarding the ablation
      success. The deviation (spatial disparity) between visualized focus origin and
      successful ablation site was 6.9 +/- 5.4 mm. Between two consecutive filter
      settings, the focus shift was more pronounced between 0.5 and 2 Hz (5.4 +/- 4.5
      mm) compared to a setting between 8 and 16 Hz (2.9 +/- 2.9 mm; P < 0.05).
      Successful ablation was achieved in 15/18 right atrial tachycardias (83%) and in
      2/3 left atrial arrhythmias. Different HPF influence NCM spatial analysis of EAT.
      However, a small variability in foci localization does not impact final ablation
      results.

PMID- 14720154
TI  - Implantable cardioverter defibrillators in adults with congenital heart disease:
      a single center experience.
AB  - Sudden death is the most frequent cause of late mortality in adults with
      congenital heart disease. This study reviews the experience of an Adult
      Congenital Heart Center with the use of implantable cardioverter defibrillators
      (ICDs). The charts of adults with congenital heart disease who had an ICD
      implantation were reviewed for diagnosis, residual lesions, reoperations, reason
      for implantation, complications, and recurrence of arrhythmias. Since 1995, 13
      patients (mean age 43 years) had an ICD implantation for aborted sudden death
      (4), and spontaneous (6), or induced (3) ventricular tachycardia. Diagnosis were
      repaired (6) or palliated (1) tetralogy of Fallot, operated pulmonary stenosis
      (2), palliated complex pulmonary atresia (1), congenitally corrected
      transposition (1), operated ventricular (1), and atrial (1) septal defects.
      Significant residual lesions included severe pulmonary regurgitation (2),
      systemic ventricular dysfunction (2), and severe pulmonary hypertension (1). Five
      patients had a QRS > 180 ms, four had a QRS < 180 ms, four had a paced rhythm.
      Overall, four (31%) patients had no ventricular dysfunction, no residual lesion,
      and QRS < 180 ms. During a mean follow-up of 29 months, seven patients had
      recurrent ventricular tachycardia, three with normal ventricular function, no
      residual lesion, and QRS < 180 ms. ICD implantation is an important adjunct in
      the management of adults with congenital heart disease. As malignant arrhythmias
      occur even in patients with no residual lesion, no QRS prolongation and no
      ventricular dysfunction, the recognition of those who would benefit from an ICD
      remains a clinical challenge.

PMID- 14720155
TI  - Use of a diode laser balloon ablation catheter to generate circumferential
      pulmonary venous lesions in an open-thoracotomy caprine model.
AB  - Electrical isolation of the pulmonary veins (PVs) can be curative in certain
      patients with atrial fibrillation. The ability of a diode laser balloon ablation
      catheter to isolate PVs was assessed in an open-thoracotomy caprine model system.
      After a median sternotomy, the left atrial appendage was cannulated in 19 goats.
      A laser balloon catheter was placed at the PV ostia and used to deliver photonic
      energy to the periostial tissue. The applications were delivered at 3.7, 4.5, or
      5.4 W/cm for 90-150 seconds. Electrical continuity of the PV with the left atrium
      was assessed using a multielectrode mapping catheter. After a single application
      of photonic energy, electrical isolation of the PVs was achieved in (70%) 19/27
      PVs. However, the success of electrical PV isolation did not correlate with the
      dose or duration of the applications. When reflectance spectroscopy was utilized
      to ensure adequate orientation and contact of the laser balloon catheter with the
      left atrial myocardium, complete PV isolation was achieved in 5/5 veins at 3.5
      W/cm for 120 seconds. Pathological examination revealed no PV stenosis, no
      pericardial damage, minor lung lesions without pleural perforation, minimal
      endothelial disruption, and, in the presence of adequate heparinization, no
      endocardial charring or overlying thrombus. Effective isolation of the PVs can be
      achieved by delivery of a continuous circular beam of photonic energy to ablate
      the left atrial - pulmonary venous junction. The use of reflectance spectroscopy
      to provide real-time monitoring of the blanching effect of balloon-tissue contact
      optimizes lesion delivery.

PMID- 14720156
TI  - A fast and simple echocardiographic method of determination of the optimal
      atrioventricular delay in patients after biventricular stimulation.
AB  - The optimization of atrioventricular (AV) delay is known to significantly
      contribute to maximum cardiac performance. The aim of this study was to validate
      a new, fast, and simple echocardiographic method of identifying the AV delay that
      provides the maximum cardiac output (CO). Right heart catheterization and Doppler
      echocardiography of transmitral filling were performed simultaneously in 18
      patients with heart failure and at least minimum functional mitral regurgitation
      treated with atrial synchronized biventricular pacing. CO derived from
      catheterization and Doppler filling parameters were measured at the predicted
      optimal AV delay (oAVD), the short AV delay (oAVD - 50 ms), and the long AV delay
      (oAVD + 28 ms on average/range, +10 ms to +50 ms) during a constant heart rate.
      The AV delay was regarded as optimal if the end of atrial contraction
      (represented by the end of A wave of transmitral filling) coincided with the
      beginning of ventricular contraction (heralded by the onset of the systolic
      component of mitral regurgitation). Prediction of the optimal AV delay included
      the following steps: (1) The maximum AV delay at which full ventricular capture
      is still preserved was found under electrocardiographic control. (2) This value,
      decreased by 5 to 10 ms, was designated as "the testing long AV delay," and the
      time interval from the end of the A wave to the onset of the systolic component
      of mitral regurgitation (time t1) was measured at this setting. (3) oAVD was
      simply calculated as "the testing long AV delay"- time t1. The CO measured at the
      oAVD (4.5 +/- 0.7 1. min-1) significantly exceeded those at the short AV delay
      (4.3 +/- 0.7 1. min-1, P < 0.01) and the long AV delay (4.4 +/- 0.8 1. min-1, P <
      0.01), respectively. The method correctly determined the maximum CO in 78% of the
      patients. In conclusion, Doppler echocardiography enables very rapid and accurate
      optimization of AV synchrony in patients after the implantation of a
      biventricular pacemaker.

PMID- 14720157
TI  - Combined therapy with steroids and antioxidants prevents ultrastructural damage
      surrounding chronic radiofrequency lesions.
AB  - We evaluated the effects of combined therapy with anti-inflammatory and
      antioxidant drugs on the healing of radiofrequency (RF) lesions (70 degrees C, 60
      s) produced in the right atrium and each ventricle of 21 adult dogs. Three groups
      were studied: acute (n= 7, sacrificed 1 hour after RF); control (n = 7,
      sacrificed 54 +/- 29 days after RF); and dogs (n = 7, sacrificed 32 +/- 5 days
      after RF) receiving combined therapy with allopurinol (400 mg p.o. 24 and 2 hours
      before RF); verapamil (200 microg/kg i.v. 15 min before and after RF);
      hydrocortisone (10 mg/kg i.v. after RF) and prednisone (20 mg p.o. for 29 days).
      Atrial (n = 37) and ventricular (n = 70) lesion dimensions were determined and 21
      right ventricular apex lesions (1 per dog) were selected for light and electron
      microscopy analysis. Histological and ultrastructural (US) characteristics in
      three zones extending from the visible lesion border, A (0-3 mm); B (3-6 mm); and
      C (6-9 mm), were assessed. In chronic groups, atrial and ventricular lesion
      dimensions were similar, but delayed scar formation was noted in treated animals.
      Acutely and at follow-up, significant US abnormalities occurred in zones A and B
      and chronic lesions exhibited type I collagen proliferation. In Zone A, the
      extent of US injury and collagen proliferation was significantly less in treated
      dogs. Further, Zone B was normal in 5/7 (71%) treated dogs and in 0/7 (0%)
      controls. Zone C was essentially normal in all groups. Combined therapy with
      steroids, verapamil, and allopurinol is effective in limiting US damage
      surrounding chronic RF lesions.

PMID- 14720158
TI  - Familial atrioventricular nodal reentry tachycardia.
AB  - Dual atrioventricular nodal pathways, the substrate responsible for
      atrioventricular node reentry tachycardia (AVNRT), are thought to be randomly
      occurring congenital anomalies. This article describes 14 patients in six
      families, each with two or three first-degree relatives with paroxysmal
      supraventricular tachycardia. Electrophysiological evidence of dual
      atrioventricular nodal pathways was established in all 13 patients studied, AVNRT
      was induced in 12 (92%), and radiofrequency ablation of the slow pathway was
      curative in all cases. The data suggest a hereditary contribution to the
      development of atrioventricular nodal pathways and AVNRT. The pattern of
      inheritance appears to be autosomal dominant.

PMID- 14720159
TI  - Mechanism of immediate recurrences of atrial fibrillation after restoration of
      sinus rhythm.
AB  - An immediate recurrence of AF may occur after restoration of sinus rhythm.
      Although pulmonary vein (PV) isolation has been shown to prevent immediate
      recurrence of AF, the specific trigger for immediate recurrence of AF has not
      been described. In 89 consecutive patients (mean age 53 +/- 11 years) who had
      sinus rhythm restored by spontaneous or transthoracic cardioversion in the course
      of a PV isolation procedure, electrograms recorded within a PV and in the
      adjacent left atrium were analyzed to determine the mechanism of initiation of
      immediate recurrence of AF. Immediate recurrence of AF was defined as a
      recurrence of AF within 90 seconds after restoration of sinus rhythm. There were
      124 episodes of immediate recurrence of AF at a mean of 18 +/- 23 seconds after
      cardioversion. Recordings within the PV that triggered the immediate recurrence
      of AF were available in 23 (19%) of the 124 immediate recurrence of AF episodes.
      Among these 23 episodes of immediate recurrence of AF, all (100%) were triggered
      by a burst of PV tachycardia (P < 0.001). The coupling interval and prematurity
      index (coupling interval/preceding sinus cycle length) of the premature
      depolarizations that did and did not trigger immediate recurrence of AF were 246
      +/- 67 ms and 0.30 +/- 0.11 vs 378 +/- 117 ms and 0.49 +/- 0.16, respectively (P
      < 0.01). Immediate recurrence of AF was abolished by PV isolation. The mechanism
      of immediate recurrence of AF is a burst of PV tachycardia, not a single
      premature depolarization. Immediate recurrence of AF identifies patients with AF
      in whom the PVs may play a major role in the initiation of AF.

PMID- 14720160
TI  - Radiofrequency ablation of atrial flutter: a randomized controlled study of two
      anatomic approaches.
AB  - Atrial flutter often results from a macroreentrant circuit that uses anatomic
      structures within the right atrium as its borders. RF ablation at the site of an
      obligatory isthmus can eliminate the atrial flutter circuit. The aim of this
      study was to compare two approaches to atrial flutter ablation: the septal
      (septal aspect of the tricuspid valve annulus to coronary sinus ostium and
      Eustachian ridge) approach versus the posterior (inferior vena cava to tricuspid
      valve annulus) approach. Twenty patients were randomized to either the "septal"
      or "posterior" approach. Entrainment mapping and/or confirmation of bidirectional
      isthmus conduction at baseline were performed in those patients in atrial flutter
      and normal sinus rhythm, respectively. RF ablation was performed with standard
      catheters and techniques. Crossover was permitted after two lines of RF lesions.
      Endpoints included acute success rates and fluoroscopy times. There was no
      statistically significant difference in the success rate between the two
      approaches using intention-to-treat analysis. Fluoroscopy times in the septal
      versus posterior approaches were 58.4 +/- 30.3 versus 70.8 +/- 31.1 minutes,
      respectively (P = 0.7). There was more frequent crossover in patients assigned to
      the septal approach and the one major complication, atrioventricular block, also
      occurred using this approach. There was no statistically significant difference
      in the success rate or fluoroscopy times between the septal and posterior
      approaches to atrial flutter ablation. However, given the risk of
      atrioventricular block with the septal approach, the posterior approach should be
      the preferred initial choice.

PMID- 14720161
TI  - Shock on T versus direct current voltage for induction of ventricular
      fibrillation: a randomized prospective comparison.
AB  - VF is induced during ICD implantation to determine efficacy of therapy.
      Establishing the best clinical method of induction of VF would potentially be
      beneficial in reducing the number of induction attempts and reducing the
      frequency of inadvertent induction of VT. Commonly used methods to induce VF
      include shock in the T wave vulnerable period (T shock) and high frequency
      stimulation. This study compared the efficacy of T shock with a new induction
      method using a 9-V DC pulse. The study was a randomized, prospective, case
      crossover trial in patients receiving ICDs. VF was induced by T shock and DC in a
      randomized sequence during an ICD implant. VF was induced at least four times in
      each patient (two T shocks and two DC inductions) and with each induction;
      attempts were continued with modifications until successful. A paired evaluation
      between the T shock/DC induction was performed in 37 patients (28 men, age 64 +/-
      12 years) with a left ventricular ejection fraction of 0.40 +/- 0.20. Arrhythmia
      indications were VT (n = 23), VF (n = 10), and VT/VF (n = 4). Drug therapy
      included amiodarone (n = 10), metoprolol (n = 6), digoxin (n = 1), and lidocaine
      (n = 1). The average T shock voltage was 207.0 +/- 16.1 V. The S1 cycle drive
      length was consistently 400 ms, and the mean S2 coupling interval was 317.8 +/-
      19.6 ms. The length of time DC applied averaged 3.8 +/- 1.4 seconds. A total of
      148 episodes of VF were included in the analysis. T shock induced VF with a cycle
      length of 213.5 +/- 35.1 ms, and DC induced VF with a cycle length of 214.6 +/-
      34.5 ms (P = 0.86). Although VF was eventually induced for each randomization,
      the number of attempts required were dependent on the method of induction. The
      successful DC first attempt VF induction rate was 96%, with three patients
      requiring two attempts during one of the DC inductions. T shock had a 68% first
      attempt success rate with 21 patients requiring multiple T shocks to induce VF.
      All nine female patients had at least one unsuccessful first attempt T shock,
      which contributed to an overall unsuccessful first attempt induction rate
      significantly higher in women then men (36.1% vs 12.5%, P = 0.001). A constant DC
      voltage induction of VF may be more effective than T shock for induction of VF in
      a clinical setting because it reduces the number of attempts required to induce
      VF. By either method, VF appears to be more difficult to induce in women. DC
      induction has the advantage of simple programming of only duration of
      stimulation. These findings have implications particularly for ICD implantation
      with conscious sedation.

PMID- 14720162
TI  - Physician heal thyself.

PMID- 14720163
TI  - Syncope in the patient with nonischemic dilated cardiomyopathy.

PMID- 14720164
TI  - A narrow complex tachycardia with ventriculoatrial dissociation after catheter
      ablation of atrioventricular nodal reentrant tachycardia:.

PMID- 14720165
TI  - Cardioverter defibrillator implantation in a child with isolated noncompaction of
      the ventricular myocardium and ventricular fibrillation.
AB  - Isolated noncompaction of the ventricular myocardium is a rare unclassified
      cardiomyopathy and is thought to be due to arrest of myocardial morphogenesis. In
      fetal life, it is characterized by an excessively prominent trabecular meshwork
      and deep intratrabecular recesses, and occurs in the left ventricle in the
      absence of structural heart disease. Echocardiography provides evidence for the
      diagnosis. The noncompacted ventricular myocardium may be accompanied by
      depressed ventricular function, systemic embolism, Wolff-Parkinson-White
      syndrome, left bundle branch block, and ventricular arrhythmia. Although onset of
      symptoms is frequently delayed until adulthood, symptomatic children have a poor
      prognosis. In this report, we describe a case of 6-year-old girl who had a
      history of recurrent syncope. Transthoracic echocardiographic examination showed
      a localized prominent trabeculation and deep intratrabecular recesses at the
      inferoapical region of the left ventricle. She had several episodes of
      ventricular fibrillation which was refractory to pharmacological treatment. An
      implantable cardioverter defibrillator (ICD) was successfully operated three
      times during follow-up.

PMID- 14720166
TI  - Wolff-Parkinson-White syndrome concomitant with asymptomatic Brugada syndrome.
AB  - A 29-year-old man was referred for electrophysiological testing and
      radiofrequency ablation because of repeated episodes of palpitation over 2 years.
      A 12-lead electrocardiogram during sinus rhythm showed manifest Wolff-Parkinson
      White syndrome and during palpitation showed narrow QRS tachycardia at a rate of
      213 beats/min. Following successful radiofrequency ablation of the left
      anterolateral accessory pathway, sustained atrial fibrillation was induced by
      atrial extrastimulation. Cibenzoline (2 mg/kg body weight) was injected to
      terminate atrial fibrillation. ST-T segment elevation in the right precordial
      leads was observed following cibenzoline administration. Ventricular fibrillation
      was reproducibly induced by ventricular extrastimuli (S1: 600 ms, S2: 220 ms, S3:
      210 ms).

PMID- 14720167
TI  - Transcutaneous implantation of an internal cardioverter defibrillator in a small
      infant with recurrent myocardial ischemia and cardiac arrest simulating sudden
      infant death syndrome.
AB  - This report describes the implantation of a transcutaneous ICD system using a
      small patch electrode in the subscapular position, and an active-can device in a
      5.3-kg infant. The indication for ICD implantation was recurrent cardiac arrest
      in the presence of normal coronary anatomy. Metabolic evaluation suggested a
      defect in fatty acid oxidation.

PMID- 14720168
TI  - Implantable cardioverter defibrillator in a child using a single subcutaneous
      array lead and an abdominal active can.
AB  - This report describes the case of an 8-year-old boy with hypertrophic
      cardiomyopathy (HCM) who underwent ICD implantation for recurrent syncope. To
      avoid vascular complications and to minimize the surgical approach in this small
      child, a nonthoracotomy ICD system was chosen using a single subcutaneous array
      lead with only one finger, an abdominally placed active can, and epicardial dual
      chamber pacing and sensing electrodes. During an 8-month follow-up, DFT was
      confirmed and there were no ventricular tachycardia or complications. It appears
      to be a safe device for the prevention of sudden cardiac death in infants and
      small children.

PMID- 14720169
TI  - Spontaneous ventricular tachycardia and fibrillation in a patient with a positive
      microvolt T wave alternans test and negative electrophysiological study.
AB  - This report describes a patient with a previous myocardial infarction who
      presented with syncope. The patient had a positive microvolt T wave alternans
      test, a negative electrophysiological study, and a normal heart rate variability.
      In hospital, the patient had episodes of ventricular tachycardia and
      fibrillation. An implantable cardioverter defibrillator was implanted and during
      the following week it discharged appropriately.

PMID- 14720170
TI  - A patient with LQTS in whom verapamil administration and permanent pacemaker
      implantation were useful for preventing torsade de pointes.
AB  - A 21-year-old woman with long QT syndrome and missense mutation in HERG (T613M),
      suffered from repeated attacks of pause dependent torsade de pointes, even though
      she was given beta-blockers and underwent stellate ganglion block twice at the
      age of eight. After she received permanent pacemaker implantation and
      administration of verapamil, no premature beats or pause dependent torsade de
      pointes was observed.

PMID- 14720171
TI  - Catheter ablation of supraventricular arrhythmias: state of the art.

PMID- 14720172
TI  - The neuropathology of frontotemporal lobar degeneration with respect to the
      cytological and biochemical characteristics of tau protein.
AB  - Pathological examinations, using a panel of tau and other antibodies, were
      performed on the brains from 55 consecutively acquired cases of frontotemporal
      lobar degeneration (FTLD). Clinically, these comprised 31 cases of frontotemporal
      dementia (FTD), 10 cases of motor neurone disease inclusion dementia (MNDID),
      seven cases of progressive aphasia (PA), four cases of semantic dementia (SD) and
      three cases of progressive apraxia (PAX). Tau pathology, in the form of
      neurofibrillary tangles (NFTs) and glial cell tangles, was present in six cases
      of FTD with parkinsonism linked to chromosome 17, five of these cases resulting
      from +16 splice-site mutation and one from +13 mutation in the tau gene. The
      insoluble tau proteins were comprised mostly of four-repeat (4-R) isoforms. Eight
      other cases of FTD, one of PA and all three cases of PAX showed tau-positive
      inclusions (Pick bodies) and swollen cells (Pick cells), characteristic of Pick's
      disease. In these cases, the insoluble tau proteins were present in most
      instances as three-repeat (3-R) tau isoforms, although two cases with a mixture
      of 3-R and 4-R isoforms were seen. One other case of FTD showed an unusual
      pathology characterized by massive extracellular deposition of tau protein,
      composed of 4-R tau isoforms, within white matter without neuronal or glial cell
      inclusions. However, 33 (60%) of 55 FTLD cases showed no tau pathology in the
      brain, except for the rare NFTs, composed of a mix of 3-R and 4-R isoforms, in
      some of the more elderly cases. Of these 33 cases, 13 had FTD, 10 had MNDID, six
      had PA and four had SD. The pathological changes present were those of a
      superficial cortical laminar microvacuolation with mild subpial and subcortical
      gliosis; the 10 MNDID cases had ubiquitin-positive inclusions in the cerebral
      cortex and hippocampus. These 33 nontau FTLD cases, along with five Alzheimer's
      disease (AD) and six Huntington's disease (HD) cases with severe pathology,
      showed a variable loss of soluble tau proteins, broadly comparable with the
      extent of neuronal loss from the cortex and loss of the intracortical perikaryal
      marker, NeuN, but unrelated to proteins within afferent projection fibres such as
      neurofilament and alpha-synuclein. Levels of tau mRNA were decreased in parallel
      in the tau-negative FTLD cases and in the severe AD and HD cases. Hence, the loss
      of tau from these 33 nontau FTLD cases is just one aspect of a neurodegenerative
      process that destroys many components of the nerve cell machinery and does not
      represent a specific disordering of the cell's ability to form tau proteins or
      incorporate these into microtubules.

PMID- 14720173
TI  - The p53 homologue p73 accumulates in the nucleus and localizes to neurites and
      neurofibrillary tangles in Alzheimer disease brain.
AB  - The molecular mechanisms that regulate neuronal survival vs. death during
      Alzheimer disease (AD) remain unclear. Nonetheless, a number of recent studies
      indicate that increased expression or altered subcellular distribution of
      numerous cell cycle proteins during AD may contribute to disease pathogenesis.
      Because homologues of p53, a key regulatory protein in the cell cycle, such as
      p73, have been identified and shown to participate in cellular differentiation
      and death pathways, we examined the expression and distribution of p73 in the
      hippocampus of eight control and 16 AD subjects. In control subjects, hippocampal
      pyramidal neurones exhibit p73 immunoreactivity that is distributed predominately
      in the cytoplasm. In AD hippocampus, increased levels of p73 are located in the
      nucleus of pyramidal neurones and p73 is located in dystrophic neurites and
      cytoskeletal pathology. Immunoblot analysis confirmed the presence of p73 in the
      hippocampus. These data indicate that p73 is expressed within hippocampal
      pyramidal neurones and exhibits altered subcellular distribution in AD.

PMID- 14720174
TI  - The glial cell response to a viral vector in the aged brain.
AB  - The normal aged brain undergoes pro-inflammatory changes. We investigated the
      effect of injecting a potential inflammatory stimulus, an adenoviral vector, on
      the response of microglia and astroglia in the aged brain. Groups of young (4
      months) and old (31 months) male C57BL/Icrfat mice received a unilateral
      injection into the striatum of adenoviral vector encoding the LacZ gene. After 48
      h, the mice were killed and the brains analysed for numbers of activated
      microglia and macrophages using the biotinylated lectin Griffonia simplicifolia
      as a marker; astroglia were identified by immunohistochemistry for glial
      fibrillary acidic protein (GFAP). The cell counts were analysed using two-way
      analysis of variance (anova). Transgene expression was assessed by beta
      galactosidase histochemistry. The numbers of activated microglia in the striatum
      increased in response to the adenovirus in both young [contralateral 19.5 (3.7),
      ipsilateral 36 (3.0)] and old [contralateral 23.1 (9.6), ipsilateral 40.8 (6.9)]
      mice (two-way anova; P < 0.0001), but there was no significant difference between
      the two age groups. There was a significant age-related increase in the number of
      GFAP-positive astroglia in the uninjected, contralateral striatum [4 months, 2.5
      (1.4); 31 months, 29.7 (9.3)] (two-way anova; P < 0.0001). However, there was no
      difference in response to the adenovirus in both young [contralateral 2.5 (1.4),
      ipsilateral 3.2 (1.2)] and old [contralateral 29.7 (9.3), ipsilateral 28.9 (8.2)]
      mice. We conclude that even though it has been argued that the aged brain is in a
      pro-inflammatory state, under the experimental conditions used in this study,
      there was no difference in the nature of the immune response between young and
      old mice of this strain to an adenoviral load.

PMID- 14720175
TI  - A novel frozen brain tissue array technique: immunohistochemical detection of
      neuronal paraneoplastic autoantibodies.
AB  - We introduce a modification of the tissue microarray technique in which several
      frozen brain tissue specimens are collected to a single frozen brain array block.
      In the present application, we use it for the detection of neuronal
      paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different
      brain regions were collected according to a standard neuropathological autopsy
      protocol. Cryostat sections from each block were cut and conventionally stained.
      From representative areas, cylinder tissue samples from each specimen were
      punched and then arrayed into a recipient array block. Using the cryostat
      sections of this brain array, autoantibodies from seven anti-Hu-positive patient
      sera (confirmed by immunoblotting) were screened by immunohistochemistry.
      Neuronal architecture was well preserved and immunohistochemical staining was
      comparable to that of conventional cryostat sections. Because of the variable
      staining pattern in different brain areas, two anti-Hu-positive sera could be
      detected immunohistochemically by the one brain array. With the present array
      technique, it is possible to characterize the variable staining patterns of
      neuronal paraneoplastic autoantibodies in different locations of the human brain.
      The frozen brain array also allows the detection of RNA and DNA targets involved
      in neurological diseases.

PMID- 14720176
TI  - Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin
      loss from cerebral cortical white matter in Alzheimer's disease.
AB  - Pathological relationships between damage to the deep white matter of the
      cerebral cortex [as evidenced by myelin loss (ML)], cerebral amyloid angiopathy
      (CAA) and arteriosclerosis (ART) were investigated in the brains of 137 patients
      with autopsy-confirmed Alzheimer's disease (AD), in order to better understand
      the causes of white matter damage in AD, and the contribution of this to the
      pathogenesis of the disorder. All 137 patients had some degree of CAA in one or
      more brain regions although the occipital cortex was severely affected by CAA
      more frequently, and consequently mean CAA severity score was significantly
      greater, than other cortical regions. Eighty-seven patients (63.5%) were affected
      by ML, with more patients showing ML from occipital cortex than from other
      cortical regions leading to a significantly higher mean ML severity score in this
      region. One hundred and twenty-six patients (92%) were affected by ART, although
      the occipital cortex was not more frequently affected by ART than other cortical
      areas, the mean ART severity score in occipital cortex was nonetheless
      significantly greater than that of frontal and temporal cortex. Eighty-seven
      patients showed both CAA and ML, although there was only a weak correlation
      between degree of CAA and extent of ML (P = 0.035). Forty-seven patients showed
      ML and significant ART, 16 patients showed significant ART but no ML, 40 patients
      showed ML in the absence of significant ART and 34 patients showed neither
      significant ART nor ML. Overall, and for each of the four brain regions, the
      extent of ML correlated significantly (P < 0.001) with degree of ART. However,
      when only those 47 patients with ML and significant ART were considered, much
      stronger correlations between the extent of ML and the degree of ART were
      achieved both overall and within each of the four brain regions. The overall ART
      severity score (and overall scores for each pathological marker of ART)
      significantly correlated with that of CAA (P < 0.001). Pathological processes
      leading to white matter damage, in terms of ML at least, in AD are thus likely to
      be heterogeneous. Many patients suffer ML in association with ART, but in others
      ML cannot be explained by presence of ART or CAA. In such patients,
      autoregulatory changes in blood vessels might be responsible for ML. The
      association between the extent of CAA and ART suggests shared risk factors for
      each pathological change.

PMID- 14720177
TI  - Differential expression of LMO4 protein in Alzheimer's disease.
AB  - The molecular bases of late-onset and sporadic Alzheimer's disease (AD) still
      have to be unraveled. Among putative candidates for molecular variations in AD,
      we propose LMO4 protein, a transcription regulator, involved in multiple protein
      complexes. We investigated changes in LMO4 immunoreactivity in vulnerable brain
      regions of AD cases and controls of comparable age. Immunocytochemical analysis
      revealed a high level of LMO4 expression in the entorhinal cortex (EC) and in the
      CA1 hippocampal region of the control brains and a consistent decrease in the AD
      brains, correlated with the amount of neurofibrillary tangles (NFT) degenerating
      neurones and the severity of senile plaques deposition. The decrease in LMO4
      immunoreactivity resulted both from weaker immunoreactive signals and from a loss
      of immunoreactive neurones. LMO4 immunocytochemical staining appeared not to be
      colocalized with NFT in a majority of neurones. Its expression was weak in the
      dentate gyrus and stronger in CA3-4, two regions with no or low numbers of NFT,
      but there was no decrease in AD compared to control cases. In the frontal cortex,
      the ventro-infero-median region (area 12) showed a greater LMO4 expression than
      the polar one (area 9), but no decrease in AD was observed. As LMO4 has been
      proposed to inhibit cellular differentiation, it can be hypothesized that a
      reduced expression is associated in EC and CA1 with attempts of diseased neurones
      to differentiate (e.g. compensatory neuritogenesis). Taken together, these data
      indicate that LMO4 protein is involved in the complexity of the disease
      phenotype, at least as a secondary factor.

PMID- 14720178
TI  - Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to
      lymph nodes in the rat.
AB  - Central nervous system (CNS) drainage may occur via connections to the
      vasculature, but in animal models up to 50% occurs via perivascular, perineural
      and primitive lymphatic drainage to cervical lymph nodes. We evaluated efflux of
      particles from the brain to cervical lymph nodes in normal rats, using Combidex
      iron oxide-based magnetic resonance imaging (MRI) agent. After intracerebral,
      intraventricular, intracarotid or intravenous injection of Combidex in normal
      Long Evans rats, particle localization was assessed by MRI and histochemistry for
      iron and the dextran coat (n = 27). Intraventricular or intracerebral injection,
      but not intracarotid administration of Combidex (100 micro g), resulted in MRI
      signal changes in the deep cervical lymph nodes around the carotid artery, and,
      less strongly, in the superficial cervical nodes. Within 2 h of Combidex
      administration, iron was histologically localized in cervical lymph nodes, with
      patched staining of capsule and peripheral sinus consistent with delivery via
      multiple afferent lymphatic vessels. Lymph node staining in groups receiving CNS
      Combidex was significantly different from controls (P < 0.0001) and was
      significantly localized in the deep vs. superficial cervical lymph nodes (P =
      0.0003). The trafficking of the superparamagnetic iron particles from the CNS in
      the rat could be visualized by MRI and histology. Combidex provides a powerful
      tool to rapidly assess drainage of virus-sized particles from the CNS.

PMID- 14720179
TI  - Systemic progesterone administration results in a partial reversal of the age
      associated decline in CNS remyelination following toxin-induced demyelination in
      male rats.
AB  - In order to establish the effects of systemically administered progesterone on
      central nervous system (CNS) remyelination, a toxin-induced model of CNS
      demyelination was used in which the rate of remyelination is age-dependent. The
      rapid remyelination in young adult rats allowed an assessment of potential
      adverse effects of progesterone while the slow remyelination in older adult rats
      allowed an assessment of its potentially beneficial effects. There was no
      significant difference in the rate of remyelination between young control and
      treated animals. However, a modest but significant increase in the extent of
      oligodendrocyte remyelination in response to progesterone (and a comparable
      significant decrease in the proportion of axons that remained demyelinated) was
      observed in older rats 5 weeks after lesion induction. We also found a
      significant increase in the proportion of Schwann cell remyelinated axons between
      3 and 5 weeks after lesion induction that was not apparent in the control
      animals. These results indicate that progesterone does not inhibit CNS
      remyelination and that it has a positive modulating effect on oligodendrocyte
      remyelination in circumstances where it is occurring sub-optimally.

PMID- 14720182
TI  - Haematophagous bats in Brazil, their role in rabies transmission, impact on
      public health, livestock industry and alternatives to an indiscriminate reduction
      of bat population.
AB  - Haematophagous bats exist only in Latin America, from Mexico to the Northern
      provinces of Argentina. They are represented by three species, Desmodus rotundus,
      Diphylla ecaudata and Diaemus youngii. While two species feed only on blood of
      wild birds, one species, D. rotundus, causes losses feeding on livestock and
      could be a vector for rabies virus. The cases in which humans were bitten by the
      bat have increased in Brazil. Bats became a target of control activities by
      farming communities and local governments. Indiscriminate actions such as
      poisoning bats and destroying their roosts put the lives of other bat species,
      which are extremely important for the ecologic balance, at risk. The vaccination
      of exposed livestock against rabies, which would protect the endangered
      livestock, is not regularly carried out. The importance and current status of D.
      rotundus in the transmission of rabies in Brazil, the Public Health aspects, the
      importance for the livestock industry are shown and the consequences of reducing
      bat population are discussed. Alternatives to an indiscriminate bat-population
      reduction in the control of rabies are proposed.

PMID- 14720183
TI  - Therapeutic effects of fig tree latex on bovine papillomatosis.
AB  - The effects of fig tree latex in treating teat papillomatosis in cow in
      comparison with salicylic acid were evaluated. For this purpose, 12 cows of 1-3
      years of age (average 2.25) affected by teat papillomatosis were divided into
      three groups. In group A, four cows were treated by fig tree (Ficus carica)
      latex; in group B, four cows were treated with 10% salicylic acid solution and in
      group C, four cows were kept as control animals receiving no treatment. Animals
      in each treatment group received their treatment once every 5 days. In groups A
      and B, de-epithelialization and shrinking of the warts began from the fifth day
      of treatment and all the warts disappeared within 30 days. However, in the
      control group no changes in the number of warts were observed until day 15 but
      thereafter a number of warts disappeared spontaneously in some of the animals.
      Both salicylic acid and fig tree latex were evaluated as having similar
      therapeutic effects in treating teat papillomatosis in cow.

PMID- 14720184
TI  - Oral vaccination against rabies and the behavioural ecology of the red fox
      (Vulpes vulpes).
AB  - As a result of oral vaccination of foxes (Vulpes vulpes) against rabies, this
      virus disease has almost been completely eradicated from West- and Central
      Europe. In most countries, vaccine baits were distributed twice a year: during
      spring (March to May) and autumn (September to October). This strategy has shown
      to be able to control and eventually eradicate rabies. However, it remains to be
      clarified if this is the most cost-effective strategy. Astonishingly, the
      behavioural ecology of the target species, the red fox, did receive only limited
      attention selecting the periods when baits should be distributed. Considering the
      behavioural ecology and rabies epidemiology of foxes, territory owners seem to
      play a key role in the spread and maintenance of rabies. Thus, oral vaccination
      campaigns should be targeted primarily at these animals. It is suggested that the
      optimal timing for bait distribution in Europe is late autumn (November) or early
      winter (December), depending on the prevailing climatic conditions. Additional
      campaigns, when financially feasible, can be implemented in order to maintain a
      high vaccination coverage during the remaining year. Furthermore, different
      baiting strategies can be selected in case of re-infection or persistent residual
      foci.

PMID- 14720185
TI  - Genital lesions in an outbreak of caprine contagious agalactia caused by
      Mycoplasma agalactiae and Mycoplasma putrefaciens.
AB  - This paper reports on the genital lesions observed in adult male and female goats
      from a commercial flock in the Extremadura region of southwestern Spain,
      following an outbreak of contagious agalactia syndrome caused by Mycoplasma
      agalactiae and M. putrefaciens. Although both species were isolated from several
      organs, M. putrefaciens was the only agent isolated from the genital lesions
      reported here, characterized by desquamative salpingitis and cystic catarrhal
      metritis in females and by testicular degeneration in males. Mycoplasma
      putrefaciens was isolated from the testes of only one of the males examined.

PMID- 14720186
TI  - Prevalence and antimicrobial resistance of Salmonella spp. in pet mammals,
      reptiles, fish aquarium water, and birds in Trinidad.
AB  - The prevalence of Salmonella spp. was determined in 970 animals comprising 423
      pet birds, 485 fish aquaria water and 62 other pets (40 pet mammals, 14 reptiles,
      eight others - crustaceans, snail, stingray) from both pet shops and households
      throughout Trinidad. The serotypes of Salmonella spp. isolated were identified
      and the resistance to various antimicrobial agents was determined. Overall nine
      (0.9%) of 970 pet animals were positive for Salmonella spp. Six isolates of
      Salmonella spp. were recovered from all pet birds with two isolates of serotype
      Aberdeen and one isolate each of Thompson, Rubislaw, Panama and Newport. The
      prevalence of Salmonella spp. in birds was 0.9%. Four isolates of Salmonella spp.
      were recovered from fish aquaria water, serotypes included Panama (two isolates),
      Newport (one isolate) and Virchow (one isolate). Prevalence of Salmonella spp.
      from fish aquaria was 0.4%. No isolate of Salmonella spp. was detected in pet
      mammals sampled while two isolates were recovered from reptiles, S. Enteritidis
      and S. Montevideo. One isolate of Salmonella spp. was recovered from a stingray,
      serotype unknown. Antimicrobial resistance was present is all animal types. The
      highest prevalence of resistance was to streptomycin among isolates from birds
      (83.3%) and other pets (100.0%) while isolates from fish aquarium water exhibited
      comparatively high resistance to cephalothin (50.0%). It was concluded that the
      isolation of Salmonella spp. from apparently healthy birds, fish aquarium water
      and other pet animals may pose a health risk to their owners and contacts as all
      serotypes are known to be potentially pathogenic depending on the oral dosage of
      the organism and the immune status of those in contact. The high prevalence of
      resistance to antimicrobial agents among Salmonella isolates across pet species
      may pose chemotherapeutic consequences to their owners and contacts.

PMID- 14720187
TI  - Genetic diversity at alkB locus in Brucella abortus.
AB  - DNA polymorphism of the alkB gene, a DNA repair gene, was assessed by PCR on
      Brucella abortus biovars 1 (strains 99, S19, 45/20, RB51 and 2308), 3 (Tulya
      strain), 5 (B3196 strain) and 6 (870 strain). A DNA repetitive element, named
      IS711, was detected in all studied biovars 1 and its complete nucleotide sequence
      was determined. We found that the element in alkB gene, bounded by 14 bp
      imperfect inverted repeats (IRs), is 840 bp long and appears to duplicate a
      consensus target site, CTAG. Analysing its nucleotide sequence of both forward
      and reverse strands, more than 10 open reading frames (ORFs) were found. Two
      potential transposase coding regions were chosen comparing all possible ORFs with
      the database. Comparing IS711 elements isolated from Brucella species, including
      both those characterized in our work and the published ones, differences in
      length and in nucleotide composition were observed among Brucella species,
      members of the same species and within the same strain. Our results confirm the
      heterogeneity of IS711 elements in Brucella genus and suggest the possibility to
      use this element to assess gene and genome diversity and to identify new
      molecular markers for Brucella species.

PMID- 14720188
TI  - Investigations into an outbreak of tuberculosis in a flock of sheep in contact
      with tuberculous cattle.
AB  - Tuberculosis, associated with Mycobacterium bovis infection, occurs infrequently
      in sheep. A sheep flock, which was potentially exposed to a high level of
      infection from in-contact tuberculous cattle, was examined for evidence of
      infection. Six sheep that had given a positive reaction to the comparative
      intradermal tuberculin test were examined post mortem. Tuberculous lesions were
      present in four of these sheep. Lesion morphology and distribution in the sheep
      was similar to that in cattle. M. bovis was cultured from the lesions and the
      isolates were strain typed by spoligotyping and variable number of tandem repeats
      (VNTR) typing. Tuberculin-reacting sheep also reacted positively to an assay for
      in vitro release of interferon-gamma. This paper describes the first report of an
      outbreak of tuberculosis in sheep in either Britain or Ireland. The report
      describes immunology and pathology findings and, using molecular typing
      techniques, suggests that the sheep had been infected from in-contact cattle.

PMID- 14720189
TI  - Use of a quantitative TaqMan-PCR for the fast quantification of mycobacteria in
      broth culture, eukaryotic cell culture and tissue.
AB  - The quantification of slow-growing mycobacteria such as Mycobacterium
      tuberculosis or M. bovis from in vitro and in vivo samples is complicated by
      their long generation time, their ability to form aggregates, and their capacity
      to persist in a state of dormancy. We compared different methods for the
      establishment of growth curves for broth cultures of M. bovis bacille Calmette
      Guerin (BCG). A quantitative TaqMan-PCR yielded results comparable with those
      obtained by protein quantification and measurement of the ATP content of the
      cultures. The quantitative TaqMan-PCR furthermore turned out to be particularly
      suitable for the measurement of multiplication of BCG within eukaryotic cells.
      Furthermore, it is a fast method allowing an estimation of the mycobacterial load
      in tissue long before colony counts can be obtained.

PMID- 14720191
TI  - Interobserver reliability in the histopathologic diagnosis of oral pre-malignant
      and malignant lesions.
AB  - BACKGROUND: The histologic classification of pre-cancerous and cancerous oral
      lesions has generally shown poor agreement between pathologists, but lesion and
      patient characteristics that may affect diagnostic reliability have not been
      explored. METHODS: Eighty-seven clinically suspicious oral lesions biopsied from
      81 patients with previous upper aerodigestive tract cancer were independently
      classified by their local pathologist and a central pathology committee.
      Interobserver reliability between the local pathologist and the central pathology
      committee was measured with weighted kappa (kappa w) statistics and corresponding
      95% confidence intervals (CI). RESULT: The kappa w for pathologic diagnosis was
      0.59 (95% CI: 0.45, 0.72), and was higher for lesions without inflammation (0.67
      (95% CI: 0.53, 0.80) than inflamed lesions (-0.10 (95% CI: -0.27, 0.07)).
      Greatest agreement was seen for lesions located in the buccal mucosa/vestibule
      (kappa w = 0.68 (95% CI: 0.46, 0.91)) and tongue (kappa w = 0.62 (95% CI: 0.40,
      0.84)). Least agreement was found for lip/labial mucosa lesions (kappa w = -0.04
      (95% CI: -0.34, 0.27)). Punch biopsies (kappa w = 0.67 (95% CI: 0.54, 0.80)) had
      greater interobserver reliability than wedge biopsies (kappa w = 0.38 (95% CI:
      0.12, 0.64)). CONCLUSIONS: These data suggest that the presence of inflammation,
      lesion site, and biopsy technique modifies the reliability of oral lesion
      histologic diagnoses.

PMID- 14720192
TI  - Growth of malignant oral epithelial stem cells after seeding into organotypical
      cultures of normal mucosa.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated both with the local
      expansion of clones of malignant cells and with their further migration to
      regional and distant sites. The interactions that occur between normal and
      malignant cells during these events are not well modelled by standard culture
      conditions, but organotypical cultures, in which epithelial cells are grown on a
      matrix containing fibroblasts, provide a suitable environment for such
      investigations. METHODS: Cells from five cell lines, each derived from OSCC and
      marked by retroviral transduction with alkaline phosphatase, were incorporated as
      small subpopulations (0.1-5%) in uniformly differentiating organotypical cultures
      constructed from normal oral mucosal cells. The patterns of growth of the
      malignant cells within the normal epithelium were examined for 3 weeks. RESULTS:
      There was variation between the different cell lines in their rates and patterns
      of growth, but all cell lines produced clusters of malignant cells that had
      expanded within 3 weeks to replace the normal epithelium. The appearance and
      spacing of these clusters suggested that each was derived from a single
      progenitor cell. The number of malignant cells initially present within a given
      area of organotypical epithelium was much greater than the number of expanding
      cell clusters subsequently formed. Cluster-forming cells thus represented only a
      subpopulation of the tumour cells. CONCLUSIONS: The organotypical model allows
      examination of interactions occurring between cells derived from OSCC and normal
      epithelia. The three-dimensional nature of organotypical cultures, together with
      their more normal patterns of differentiation, provides an environment that more
      closely mimics the in vivo environment in which tumours develop. The finding that
      only a subpopulation of tumour cells forms expanding tumour colonies suggests a
      range of growth potentials within a tumour population and may provide preliminary
      evidence for some form of stem and amplifying cell pattern.

PMID- 14720193
TI  - Establishment of OC3 oral carcinoma cell line and identification of NF-kappa B
      activation responses to areca nut extract.
AB  - BACKGROUND: Cell lines derived from oral squamous cell carcinoma (OSCC) exposed
      to variable etiological factors can bestow advantages in understanding the
      molecular and cellular alterations pertaining to environmental impacts. Most OSCC
      cell lines have been established from smoker patients or areca chewing/smoker
      patients, carrying the genomic alterations in p53. METHODS: A new cell line, oral
      carcinoma 3 (OC3), was established from an OSCC in a long-term areca (betel)
      chewer who does not smoke. Cellular and molecular features of OC3 were determined
      by variable assays. RESULTS: The cultured monolayer cells were mainly polygonal
      and had the expression of cytokeratin 14. The chromosomal analysis using
      comparative genomic hybridization has revealed the gain in chromosomes 1q, 5q,
      and 8q, the loss in 4q, 6p, and 8p as well as the gain of entire chromosome 20.
      Loss of heterozygosity and instability in multiple microsatellite markers in
      chromosome 4q were also noted. OC3 cells bear wild-type p53 coding sequence and
      have a high level of p53 expression. Its p21 expression was similar to that in
      normal human oral keratinocyte (NHOK). Interestingly, activation of nuclear
      factor kappa B (NF-kappa B) in OC3 cells following the treatment of areca nut
      extract was observed. CONCLUSION: OC3 cell line could be valuable in
      understanding the genetic impairments and phenotypic changes associated with
      areca in oral keratinocyte.

PMID- 14720194
TI  - Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate
      proteoglycan reflects dysplastic changes of the oral mucosal epithelium.
AB  - BACKGROUND: Intercellular deposition of perlecan, a major heparan sulfate
      proteoglycan (HSPG) of the basement membrane, is known to result in
      characteristic stellate reticulum-like structures in ameloblastomas or tooth
      germs. Although enlargement of the intercellular space is one of the histological
      characteristics of epithelial dysplasia of oral mucosa, the mode of expression of
      perlecan is poorly understood in these epithelial lesions. METHODS: Eighty-two
      biopsy specimens consisting of normal and hyperplastic epithelium, epithelial
      dysplasia, and squamous cell carcinomas were examined for both perlecan core
      protein and heparan sulfate (HS) chains by immunohistochemistry and in situ
      hybridization. RESULTS: In normal and hyperplastic epithelium, perlecan core
      protein and HS chains were localized in the cell border of parabasal cells and
      lower prickle cells, and HS chains were also found in basal cells. With an
      increase in the severity of epithelial dysplasia, the core protein was heavily
      and extensively deposited in the interepithelial space as well as in the
      cytoplasm of epithelial cells from the basal to the surface layers. Its gene
      expression was confirmed in the cells around the protein deposits. On the other
      hand, HS chains were enhanced in mild dysplasia, but decreased in moderate and
      severe dysplasias. In squamous cell carcinomas, either the core protein or HS
      chains were found scarcely in tumor cells but abundantly in the stromal space.
      CONCLUSIONS: The findings indicate that perlecan is localized in the
      intercellular space of the oral epithelia, and that it is over-expressed in
      dysplastic epithelial cells and is deposited in their interepithelial space,
      which results in the histology of reduction of cellular cohesion.

PMID- 14720195
TI  - Mdm2 mRNA expression in salivary gland tumour cell lines.
AB  - BACKGROUND: Murine double minute 2 (mdm2) is a cellular protooncogene, which, in
      conditions of overexpression or amplification, is capable of inactivating the
      functions of p53, leading to tumorigenesis. Immunoexpression of mdm2 in salivary
      gland tumours was previously found; however, it was necessary to find out if mdm2
      was overexpressed. The aim of this study was to analyse the mRNA expression of
      mdm2 in salivary gland neoplasms and to correlate it to immunoexpression of p53
      and p21 proteins. METHODS: Specimens of different salivary gland neoplasms were
      obtained from surgical resections, and cell lineages derived from these tissues
      were established. RNA extraction was performed and mRNA expression was
      investigated using reverse transcription-polymerase chain reaction (RT-PCR).
      Cellular expression of p53 and p21 proteins was investigated by
      immunofluorescence technique. RESULTS: Increased expression of mdm2 was found in
      the majority of cell lines analysed. CONCLUSIONS: Comparing all results, we
      postulated that overexpression of mdm2 is related to the tumorigenesis and/or
      tumour progression of salivary gland neoplasms.

PMID- 14720196
TI  - Involvement of tumor necrosis factor-alpha and interleukin-8 in antigen-induced
      arthritis of the rabbit temporomandibular joint.
AB  - BACKGROUND: In temporomandibular joint (TMJ) arthritis, knowledge is limited
      about the source of the inflammatory mediators. The aim of this study was to
      investigate the immunohistochemical role of tumor necrosis factor-alpha (TNF
      alpha) and interleukin-8 (IL-8) in the development of the antigen-induced
      arthritis of the rabbit TMJ. METHODS: Unilateral TMJ arthritis was induced in 28
      adult rabbits. From 6 h to 6 weeks after induction of arthritis, the topology of
      TNF-alpha and IL-8 was observed. RESULTS: Positive reaction for TNF-alpha of
      synovial cells was observed within 3 days after induction and at 3 weeks after
      induction. TNF-alpha positive vascular endothelial cells and chondrocytes were
      identified throughout the observation period. IL-8 was detected only during the
      acute stage. CONCLUSIONS: The cytokines TNF-alpha and IL-8 were observed in
      specific cells depending on the stage. TNF-alpha was particularly related with
      angiogenesis and cartilage destruction and IL-8 was involved in the acute stage
      of inflammation.

PMID- 14720197
TI  - Systemic capsaicin for burning mouth syndrome: short-term results of a pilot
      study.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is a major diagnostic and therapeutic
      problem. Systemic and topical treatments (capsaicin, lidocaine, anti-histamines,
      sucralfate and benzydiamine) have been tried, but they appear to be inadequate.
      Topical capsaicin is bitter, may cause burning and has low therapeutic efficacy.
      We hypothesized that systemic administration of capsaicin could reduce the
      limitations of topical administration and have better therapeutic efficacy; this
      hypothesis was tested in a controlled trial. METHODS: Systemic oral capsaicin
      0.25% was used for patients with BMS, recruited in our single centre. After the
      diagnosis of BMS, patients were dentally and medically examined. They were
      alternatively assigned to treatment with capsaicin or to a
      shape/smell/taste/color matched placebo. The severity of symptoms was scored at
      trial entry and 30 days thereafter by investigators who were unaware of the
      assigned intervention. The visual analogical scale (VAS) measure was used to
      score the severity of pain, and results for the treated and untreated groups were
      compared by Fisher's exact test. Analysis was performed by intention-to-treat.
      Statistical significance was considered for values of P < 0.05. Data are
      expressed as mean +/- SD. RESULTS: Fifty patients were enrolled (25 assigned to
      systemic capsaicin and 25 to placebo). The VAS score was significantly lower in
      treated patients (5.84 +/- 1.17) as compared to the placebo-control group (6.24
      +/- 0.96). The use of systemic capsaicin implied significant gastric toxicity
      (referred gastric pain) with eight cases (32%) documented in the treatment group
      as compared to zero cases (0%) in the placebo control group. CONCLUSION: Systemic
      capsaicin is therapeutically effective for the short-term treatment of BMS but
      major gastrointestinal side-effects may threaten its large-scale, long-term use.
      This preliminary study suggests that more, adequately powered, randomized
      controlled trials are necessary and worthy to come to a definitive assessment of
      this matter.

PMID- 14720198
TI  - Orofacial granulomas after injection of cosmetic fillers. Histopathologic and
      clinical study of 11 cases.
AB  - BACKGROUND: Purposely, cosmetic injections in orofacial tissues of various
      resorbable, biodegradable, or permanent fillers may be followed by development of
      foreign-body granulomas. The aim of this article is to contribute to the
      histologic identification of the filler material. METHODS: Histologic and
      clinical features of 11 cases of granulomas on orofacial fillers are described.
      RESULTS: Only 3/11 patients knew the nature of the injected product. Four
      histologic patterns were found: (i) Artecoll, (ii) Dermalive, and (iii) New-Fill
      granuloma, all three of the classic giant cell granuloma type, differing in
      respect of foreign particles; and (iv) Liquid Silicone granuloma, which featured
      a cystic and macrophagic type. Information was often missing or misleading,
      patients or practitioners being reluctant to give the details. CONCLUSION:
      Increasing demand for orofacial tissue augmentation makes pathologists face new,
      and sometimes, puzzling granuloma types. Identification of the foreign product
      might be required for therapeutic or medico-legal reasons.

PMID- 14720199
TI  - Primary intraosseous odontogenic carcinoma with osteoid/dentinoid formation.
AB  - Primary intraosseous carcinoma/odontogenic carcinomas are extremely rare
      malignant odontogenic tumours that are thought to arise from residues of
      odontogenic epithelium. An unusual case of primary intraosseous carcinoma arising
      de novo in a previously unreported site of posterior maxilla is described. The
      tumour was characterized by sheets of pleomorphic round-to-ovoid cells and marked
      osteoid/dentinoid formation with foci of globular mineralization.

PMID- 14720200
TI  - Solid variant of odontogenic keratocyst.
AB  - A case of an unusual lesion from the maxilla is presented. Macroscopically, the
      lesion was solid and histologically consisted of 'multiple separate keratocysts'
      of varying size that infiltrated into the surrounding bone and soft tissues.
      Panoramic image and CT scans showed a multilocular honeycomb ill-defined
      radiolucency with infiltration into the maxillary sinus and floor of orbit. This
      lesion should be differentiated from similar odontogenic lesions, such as
      keratoameloblastoma and papilliferous keratoameloblastoma. As there was no
      evidence of follicles, islands of ameloblastoma, or papilliferous structures in
      the entire specimen, the lesion could not be diagnosed as either a
      keratoameloblastoma or a papilliferous keratoameloblastoma. The invasive and
      destructive growth behavior, the histopathological features, and the
      histochemical pattern of the collagen stroma imply that this solid lesion is a
      neoplasia. It is suggested that the proper term for this lesion is solid variant
      of odontogenic keratocyst.

PMID- 14720201
TI  - The contributions of excitotoxicity, glutathione depletion and DNA repair in
      chemically induced injury to neurones: exemplified with toxic effects on
      cerebellar granule cells.
AB  - Six chemicals, 2-halopropionic acids, thiophene, methylhalides, methylmercury,
      methylazoxymethanol (MAM) and trichlorfon (Fig. 1), that cause selective necrosis
      to the cerebellum, in particular to cerebellar granule cells, have been reviewed.
      The basis for the selective toxicity to these neurones is not fully understood,
      but mechanisms known to contribute to the neuronal cell death are discussed. All
      six compounds decrease cerebral glutathione (GSH), due to conjugation with the
      xenobiotic, thereby reducing cellular antioxidant status and making the cells
      more vulnerable to reactive oxygen species. 2-Halopropionic acids and
      methylmercury appear to also act via an excitotoxic mechanism leading to elevated
      intracellular Ca2+, increased reactive oxygen species and ultimately impaired
      mitochondrial function. In contrast, the methylhalides, trichlorfon and MAM all
      methylate DNA and inhibit O6-guanine-DNA methyltransferase (OGMT), an important
      DNA repair enzyme. We propose that a combination of reduced antioxidant status
      plus excitotoxicity or DNA damage is required to cause cerebellar neuronal cell
      death with these chemicals. The small size of cerebellar granule cells, the
      unique subunit composition of their N-methyl-d-aspartate (NMDA) receptors, their
      low DNA repair ability, low levels of calcium-binding proteins and vulnerability
      during postnatal brain development and distribution of glutathione and its
      conjugating and metabolizing enzymes are all important factors in determining the
      sensitivity of cerebellar granule cells to toxic compounds.

PMID- 14720202
TI  - Secretion of locally synthesized neurohormone from neurites of peptidergic
      neurons.
AB  - Local protein synthesis in neuronal processes is a common phenomenon and may play
      an important role in synaptic plasticity and hormonal regulation. We have used
      neuroendocrine bag cells of Aplysia californica as a model system to study local
      protein synthesis. In our previous work we found that bag cell neurites are
      capable of synthesizing and processing the prohormone of egg-laying hormone (pro
      ELH). In the present study, we found that bag cell neurites are also capable of
      releasing locally synthesized pro-ELH and ELH-related products via both
      constitutive and regulated pathways. However, an electrical afterdischarge did
      not enhance local pro-ELH synthesis, as it does in the bag cell soma. This is the
      first evidence that isolated neurites are capable of secreting locally
      synthesized proteins.

PMID- 14720203
TI  - Genetic and pharmacological inactivation of the adenosine A2A receptor attenuates
      3-nitropropionic acid-induced striatal damage.
AB  - Adenosine A2A receptor (A2AR) antagonism attenuates 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced dopaminergic neurodegeneration and quinolinic acid
      induced excitotoxicity in the neostriatum. As A2ARs are enriched in striatum, we
      investigated the effect of genetic and pharmacological A2A inactivation on
      striatal damage produced by the mitochondrial complex II inhibitor 3
      nitropriopionic acid (3-NP). 3-NP was administered to A2AR knockout (KO) and wild
      type (WT) littermate mice over 5 days. Bilateral striatal lesions were analyzed
      from serial brain tissue sections. Whereas all of the 3-NP-treated WT mice
      (C57BL/6 genetic background) had bilateral striatal lesions, only one of eight of
      the 3-NP-treated A2AR KO mice had detectable striatal lesions. Similar
      attenuation of 3-NP-induced striatal damage was observed in A2AR KO mice in a 129
      Steel background. In addition, the effect of pharmacological antagonism on 3-NP
      induced striatal neurotoxicity was tested by pre-treatment of C57Bl/6 mice with
      the A2AR antagonist 8-(3-chlorostyryl) caffeine (CSC). Although bilateral
      striatal lesions were observed in all mice treated either with 3-NP alone or 3-NP
      plus vehicle, there were no demonstrable striatal lesions in mice treated with
      CSC (5 mg/kg) plus 3-NP and in five of six mice treated with CSC (20 mg/kg) plus
      3-NP. We conclude that both genetic and pharmacological inactivation of the A2AR
      attenuates striatal neurotoxicity produced by 3-NP. Since the clinical and
      neuropathological features of 3-NP-induced striatal damage resemble those
      observed in Huntington's disease, the results suggest that A2AR antagonism may be
      a potential therapeutic strategy in Huntington's disease patients.

PMID- 14720204
TI  - Proteasome inhibition and aggregation in Parkinson's disease: a comparative study
      in untransfected and transfected cells.
AB  - Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in
      Parkinson's disease (PD) and other neurodegenerative disorders. We have
      investigated the effect of UPS inhibition on the metabolism of alpha-synuclein
      (SYN) and parkin, two proteins genetically and histopathologically associated to
      PD. Pharmacological inhibition of proteasome induced accumulation of both parkin
      and SYN in transfected PC12 cells. We found that this effect was caused by
      increased protein synthesis rather than impairment of protein degradation,
      suggesting that inhibition of the UPS might lead to non-specific up-regulation of
      cytomegalovirus (CMV)-driven transcription. To investigate whether endogenous
      parkin and SYN can be substrate of the UPS, untransfected PC12 cells and primary
      mesencephalic neurones were exposed to proteasome inhibitors, and parkin and SYN
      expression was evaluated at both protein and mRNA level. Under these conditions,
      we found that proteasome inhibitors did not affect the level of endogenous parkin
      and SYN. However, we confirmed that dopaminergic neurones were selectively
      vulnerable to the toxicity of proteasome inhibitors. Our results indicate that
      studies involving the use of proteasome inhibitors, particularly those in which
      proteins are expressed from a heterologous promoter, are subjected to potential
      artefacts that need to be considered for the interpretation of the role of UPS in
      PD pathogenesis.

PMID- 14720205
TI  - Amyloid-beta-induced toxicity of primary neurons is dependent upon
      differentiation-associated increases in tau and cyclin-dependent kinase 5
      expression.
AB  - It has previously been reported that amyloid-beta (Abeta) peptide is neurotrophic
      to undifferentiated but neurotoxic to differentiated primary neurons. The
      underlying reasons for this differential effect is not understood. Recently, the
      toxicity of Abeta to neurons was shown to be dependent upon the activation of
      cyclin-dependent kinase 5 (Cdk5), thought to promote tau phosphorylation that
      leads to cytoskeletal disruption, morphological degeneration and apoptosis. Here
      we report that Cdk5, tau, and phosphorylated-tau (P-tau) are expressed at very
      low levels in undifferentiated primary neurons, but that the expression of Cdk5
      and tau and the phosphorylation of tau increase markedly between 4 and 8 days of
      differentiation in vitro. Tau expression decreased after this time, as did the
      level of P-tau, to low levels by 17 days. Abeta induced tau phosphorylation of
      neurons only after >or= 4 days of differentiation, a time that coincides with the
      onset of Abeta toxicity. Blocking tau expression (and therefore tau
      phosphorylation) with an antisense oligonucleotide completely blocked Abeta
      toxicity of differentiated primary neurons, thereby confirming that tau was
      essential for mediating Abeta toxicity. Our results demonstrate that
      differentiation-associated changes in tau and Cdk-5 modulate the toxicity of
      Abeta and explain the opposite responses of differentiated and undifferentiated
      neurons to Abeta. Our results predict that only cells containing appreciable
      levels of tau are susceptible to Abeta-induced toxicity and may explain why Abeta
      is more toxic to neurons compared with other cell types.

PMID- 14720206
TI  - Up-regulation of NMDAR1 subunit gene expression in cortical neurons via a PKA
      dependent pathway.
AB  - Transcription mediated by protein kinase A and the cAMP response element binding
      protein (CREB) has been linked to the establishment of long-term memory and cell
      survival. However, all of the major targets for activated CREB have yet to be
      identified. Given the fact that CREB-mediated transcription is intimately
      involved in cellular processes of learning and memory and that CREB activity can
      be regulated by synaptic N-methyl-d-aspartate receptors (NMDARs) and metabotropic
      GABA receptors, we have studied the role of the cAMP-dependent signaling pathway
      in the regulation of the NMDA receptor subunit 1 (NMDAR1), a subunit required for
      functional receptor formation. We now report that levels of NMDAR1 subunit
      protein in primary neocortical cultures are increased 66% in response to
      forskolin, an activator of adenylyl cyclase. Up-regulation of NMDAR1 is
      paralleled by a twofold increase in mRNA levels and an 83% increase in NMDAR1
      promoter/luciferase reporter activity that is dependent on protein kinase A.
      Three cAMP regulatory elements (CREs) in the rat NMDAR1 promoter (- 228, - 67,
      and - 39) bind CREB in vitro and forskolin increases binding to two of the sites
      (- 228 and - 67). Chromatin immunoprecipitation of neuronal rat genomic DNA
      reveals that CREB is bound in vivo to the endogenous NMDAR1 gene. Increased
      presence of the activated Ser133 phosphorylated form is dependent on the length
      of exposure to forskolin. Taken together with the results of mutational analysis,
      the findings strongly suggest that transcription of NMDAR1 is regulated by the c
      AMP signaling pathway, most likely through the binding of CREB and its activation
      by signal-dependent phosphorylation.

PMID- 14720207
TI  - Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a
      transgenic mouse model of amyotrophic lateral sclerosis.
AB  - There is substantial evidence implicating both inflammation and mitochondrial
      dysfunction in amyotrophic lateral sclerosis (ALS) pathogenesis. We investigated
      the therapeutic effects of cyclooxygenase 2 (COX-2) inhibitors both alone and in
      combination with creatine in the G93A transgenic mouse model of ALS. Oral
      administration of either celecoxib or rofecoxib significantly improved motor
      performance, attenuated weight loss and extended survival. The administration of
      COX-2 inhibitors significantly reduced prostaglandin E2 levels at 110 days of
      age. The combination of creatine with COX-2 inhibitors produced additive
      neuroprotective effects and extended survival by approximately 30%. The COX-2
      inhibitors significantly protected against depletion of anterior horn motor
      neurons and creatine with COX-2 inhibitors showed greater protection than COX-2
      inhibitors alone. These results suggest that combinations of therapies targeting
      different disease mechanisms may be a useful strategy in the treatment of ALS.

PMID- 14720208
TI  - The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide
      mediated expression of inducible nitric oxide synthase.
AB  - Lipopolysaccharide (LPS) and interferon-gamma (IFN) treatment of C6 rat glioma
      cells increased the intracellular ceramide level and the expression of the
      inducible nitric oxide synthase (iNOS) gene. To delineate the possible role of
      ceramide in the induction of iNOS, we examined the source of intracellular
      ceramide and associated signal transduction pathway(s) with the use of inhibitors
      of intracellular ceramide generation. The inhibitor of neutral sphingomyelinase
      (3-O-methylsphingomyelin, MSM) inhibited the induction of iNOS, whereas inhibitor
      of acidic sphingomyelinase (SR33557) or that of ceramide de novo synthesis
      (fumonisin B1) had no effect on the induction of iNOS. MSM-mediated inhibition of
      iNOS induction was reversed by the supplementation of exogenous C8-ceramide,
      suggesting that ceramide production by neutral sphingomyelinase (nSMase) is a key
      mediator in the induction of iNOS. The MSM-mediated inhibition of iNOS gene
      expression correlated with the decrease in the activity of ras. Inhibition of co
      transfected iNOS promoter activity by dominant negative ras supported the role of
      ras in the nSMase-dependent regulation of iNOS gene. NF-kappaB DNA binding
      activity and its transactivity were also reduced by MSM pretreatment, and were
      completely reversed by the supplementation of C8-ceramide. As the dominant
      negative ras also reduced NF-kappaB transactivity, NF-kappaB activation may be
      downstream of ras. Our results suggest that ceramide generated by nSMase may be a
      critical mediator in the regulation of iNOS gene expression via ras-mediated NF
      kappaB activation under inflammatory conditions.

PMID- 14720209
TI  - Reduced contribution from Na+/H+ exchange to acid extrusion during anoxia in
      adult rat hippocampal CA1 neurons.
AB  - The effect of anoxia on Na+/H+ exchange activity was examined in acutely isolated
      adult rat hippocampal CA1 neurons loaded with the H+-sensitive fluorophore,
      BCECF. Five-minute anoxia imposed under nominally HCO3-/CO2-free conditions
      induced a fall in pHi, the magnitude of which was smaller following prolonged
      exposure to medium in which N-methyl-D-glucamine (NMDG+) was employed as an
      extracellular Na+ (Na(+)(o)) substitute. Also consistent with the possibility
      that Na+/H+ exchange becomes inhibited soon after the induction of anoxia, rates
      of Na(+)(o)-dependent pHi recovery from internal acid loads imposed during anoxia
      were slowed, compared to rates of Na(+)(o)-dependent pHi recovery observed prior
      to anoxia. At the time at which rates of pHi recovery were reduced during anoxia,
      cellular adenosine triphosphate (ATP) levels had fallen to 35% of preanoxic
      levels, suggesting that ATP depletion might contribute to the observed inhibition
      of Na+/H+ exchange. In support, incubation of neurons with 2-deoxyglucose and
      antimycin A under normoxic conditions induced a fall in cellular ATP levels that
      was also associated with reduced Na(+)(o)-dependent rates of pHi recovery from
      imposed acid loads; conversely, pre-treatment with 10 mm creatine attenuated the
      effects of anoxia to reduce both ATP levels and Na(+)(o)-dependent rates of pHi
      recovery from internal acid loads. Taken together, the results are consistent
      with the possibility that functional Na+/H+ exchange activity in adult rat CA1
      neurons declines soon after the onset of anoxia, possibly as a result of anoxia
      induced falls in intracellular ATP.

PMID- 14720210
TI  - Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and
      cultured neurons after amyloid-beta exposure.
AB  - Calsenilin/DREAM/KChIP3 was identified as a calcium-binding protein that
      interacts with presenilins, serves as a transcription repressor, and binds to the
      A-type potassium channel. In this study, we hypothesized that calsenilin might be
      involved in the neurodegeneration of Alzheimer's disease and examined calsenilin
      expression in Alzheimer's disease. Calsenilin levels were elevated in the cortex
      region of Alzheimer's patient brains and in the neocortex and the hippocampus of
      Swedish mutant beta-amyloid precursor protein transgenic mice brains. Induction
      of calsenilin was also observed in the activated astroglia as well as in the
      neurons surrounding beta-amyloid (Abeta)- and Congo red-positive plaques.
      Exposing cultured cortical and hippocampal neurons to Abeta42, an amyloid-beta
      peptide whose deposition in the brain is a characteristic of Alzheimer's disease,
      induced both calsenilin protein and mRNA expression, and cell death. Moreover,
      blocking the calsenilin expression protected the neuronal cells from Abeta
      toxicity. These findings suggest that chronic up-regulation of calsenilin may be
      a risk factor for developing Alzheimer's disease, perhaps by facilitating
      calsenilin-mediated neurodegeneration.

PMID- 14720211
TI  - Leucine-nitrogen metabolism in the brain of conscious rats: its role as a
      nitrogen carrier in glutamate synthesis in glial and neuronal metabolic
      compartments.
AB  - The source of nitrogen (N) for the de novo synthesis of brain glutamate,
      glutamine and GABA remains controversial. Because leucine is readily transported
      into the brain and the brain contains high activities of branched-chain
      aminotransferase (BCAT), we hypothesized that leucine is the predominant N
      precursor for brain glutamate synthesis. Conscious and unstressed rats
      administered with [U-13C] and/or [15N]leucine as additions to the diet were
      killed at 0-9 h of continuous feeding. Plasma and brain leucine equilibrated
      rapidly and the brain leucine-N turnover was more than 100%/min. The isotopic
      dilution of [U-13C]leucine (brain/plasma ratio 0.61 +/- 0.06) and [15N]leucine
      (0.23 +/- 0.06) differed markedly, suggesting that 15% of cerebral leucine-N
      turnover derived from proteolysis and 62% from leucine synthesis via reverse
      transamination. The rate of glutamate synthesis from leucine was 5 micro mol/g/h
      and at least 50% of glutamate-N originally derived from leucine. The enrichment
      of [5-15N]glutamine was higher than [15N]ammonia in the brain, indicating glial
      ammonia generation from leucine via glutamate. The enrichment of [15N]GABA,
      [15N]aspartate, [15N]glutamate greater than [2-15N]glutamine suggests direct
      incorporation of leucine-N into both glial and neuronal glutamate. These findings
      provide a new insight for the role of leucine as N-carrier from the plasma pool
      and within the cerebral compartments.

PMID- 14720212
TI  - A liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein E
      expression, secretion and cholesterol homeostasis in astrocytes.
AB  - Apolipoprotein E (apoE) is an important protein involved in lipoprotein clearance
      and cholesterol redistribution. ApoE is abundantly expressed in astrocytes in the
      brain and is closely linked to the pathogenesis of Alzheimer's disease (AD). We
      report here that small molecule ligands that activate either liver X receptors
      (LXR) or retinoid X receptor (RXR) lead to a dramatic increase in apoE mRNA and
      protein expression as well as secretion of apoE in a human astrocytoma cell line
      (CCF-STTG1 cells). Examination of primary mouse astrocytes also revealed
      significant induction of apoE mRNA, and protein expression and secretion
      following incubation with LXR/RXR agonists. Moreover, treatment of mice with a
      specific synthetic LXR agonist T0901317 resulted in up-regulation of apoE mRNA
      and protein in both hippocampus and cerebral cortex, indicating that apoE
      expression in brain can be up-regulated by LXR agonists in vivo. Along with a
      dramatic induction of ABCA1 cholesterol transporter expression, these ligands
      effectively mediate cholesterol efflux in both CCF-STTG1 cells and mouse
      astrocytes in the presence or absence of apolipoprotein AI (apoAI). Our studies
      provide strong evidence that small molecule LXR/RXR agonists can effectively
      mediate apoE synthesis and secretion as well as cholesterol homeostasis in
      astrocytes. LXR/RXR agonists may have significant impact on the pathogenesis of
      multiple neurological diseases, including AD.

PMID- 14720213
TI  - Lipopolysaccharide-induced increase in signalling in hippocampus is abrogated by
      IL-10--a role for IL-1 beta?
AB  - Parenterally administered lipopolysaccharide (LPS) increases the concentration of
      the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the rat hippocampus
      and evidence suggests that this effect plays a significant role in inhibiting
      long-term potentiation (LTP). The anti-inflammatory cytokine IL-10, antagonizes
      certain effects of IL-1beta, so if the effects of LPS are mediated through an
      increase in IL-1beta, it might be predicted that IL-10 would also abrogate the
      effect of LPS. Here, we report that IL-10 reversed the inhibitory effect of LPS
      on LTP and the data couple this with an inhibitory effect on the LPS-induced
      increase in IL-1beta. LPS treatment increased hippocampal expression of IL-1
      receptor Type I protein. Consistent with the LPS-induced increases in IL-1beta
      concentration and receptor expression, were downstream changes which included
      enhanced phosphorylation of IRAK and the stress-activated kinases, JNK and p38;
      these LPS-induced changes were reversed by IL-10, which concurs with the idea
      that these events are triggered by increased activation of IL-1RI by IL-1beta. We
      provide evidence which indicates that LPS treatment leads to evidence of cell
      death and this was reversed in hippocampus prepared from LPS-treated rats which
      received IL-10. The evidence is therefore consistent with the idea that IL-10
      acts to protect neuronal tissue from the detrimental effects induced by LPS.

PMID- 14720214
TI  - Mitogen-activated protein kinase/extracellular signal-regulated kinase attenuates
      3-hydroxykynurenine-induced neuronal cell death.
AB  - 3-Hydroxykynurenine (3-HK), an endogenous tryptophan metabolite, is known to have
      toxic effects in brain. However, the molecular mechanism of the toxicity has not
      been well identified. In this study, we investigated the involvement of
      MAPK/extracellular signal-regulated kinase (ERK) in the 3-HK-induced neuronal
      cell damage. Our results showed that 3-HK induced apoptotic neuronal cell death
      and ERK phosphorylation occurred during cell death. Inhibition of ERK activation
      using PD98059 considerably increased cell death. Furthermore, cell death was
      preceded by mitochondrial malfunction including collapse of mitochondrial
      membrane potential (DeltaPsi(m)) and cytochrome c release from mitochondria to
      the cytosol. Interestingly, inhibition of ERK dramatically increased
      mitochondrial malfunction, and enhanced caspase activation, resulting in enhanced
      neuronal cell death. Thus, our results show that ERK plays a protective role by
      maintaining mitochondrial function and regulating caspase activity under
      conditions of cellular stress.

PMID- 14720215
TI  - Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis,
      specific respiratory chain defects, and efficacious antioxidant therapy in
      superoxide dismutase 2 null mice.
AB  - Oxidative stress and mitochondrial dysfunction have been linked to
      neurodegenerative disorders such as Parkinson's and Alzheimer's disease. However,
      it is not yet understood how endogenous mitochondrial oxidative stress may result
      in mitochondrial dysfunction. Most prior studies have tested oxidative stress
      paradigms in mitochondria through either chemical inhibition of specific
      components of the respiratory chain, or adding an exogenous insult such as
      hydrogen peroxide or paraquat to directly damage mitochondria. In contrast, mice
      that lack mitochondrial superoxide dismutase (SOD2 null mice) represent a model
      of endogenous oxidative stress. SOD2 null mice develop a severe neurological
      phenotype that includes behavioral defects, a severe spongiform encephalopathy,
      and a decrease in mitochondrial aconitase activity. We tested the hypothesis that
      specific components of the respiratory chain in the brain were differentially
      sensitive to mitochondrial oxidative stress, and whether such sensitivity would
      lead to neuronal cell death. We carried out proteomic differential display and
      examined the activities of respiratory chain complexes I, II, III, IV, V, and the
      tricarboxylic acid cycle enzymes alpha-ketoglutarate dehydrogenase and citrate
      synthase in SOD2 null mice in conjunction with efficacious antioxidant treatment
      and observed differential sensitivities of mitochondrial proteins to oxidative
      stress. In addition, we observed a striking pattern of neuronal cell death as a
      result of mitochondrial oxidative stress, and were able to significantly reduce
      the loss of neurons via antioxidant treatment.

PMID- 14720216
TI  - Loss of alpha-conotoxinMII- and A85380-sensitive nicotinic receptors in
      Parkinson's disease striatum.
AB  - Multiple nicotinic receptors are present in rodent and monkey striatum, with a
      selective localization of alpha-conotoxinMII-sensitive sites in the striatum and
      preferential declines in their numbers after nigrostriatal damage. Here we report
      the presence of 125I-alpha-conotoxinMII and alpha-conotoxinMII-sensitive 125I
      epibatidine nicotinic receptors in human control and Parkinson's disease
      striatum. 125I-alpha-ConotoxinMII bound to control striatum with the
      characteristics of a nicotinic receptor ligand although the number of sites was
      approximately fivefold lower than in rodent and monkey. Competition analyses of
      alpha-conotoxinMII with 125I-epibatidine showed that toxin-sensitive sites
      comprised approximately 15% of nicotinic receptors in human striatum. In
      Parkinson's disease caudate, there was a approximately 50% decline in 125I-alpha
      conotoxinMII sites with a similar decline in the dopamine transporter. In
      putamen, there were substantially greater losses of the dopamine transporter (80
      90%) but only 50-60% decreases in 125I-alpha-conotoxinMII sites with
      corresponding declines in alpha-conotoxinMII-sensitive 125I-epibatidine sites,
      125I-epibatidine (multiple) sites and 125I-A85380 (beta2-containing) nicotinic
      receptors. The greater loss of the transporter compared with nicotinic sites
      suggests that only a subpopulation of nicotinic receptors is located pre
      synaptically on striatal dopaminergic neurons in man. Correlation analyses
      between changes in nicotinic receptors and the dopamine transporter in
      Parkinson's disease striatum suggest that alpha-conotoxinMII-sensitive 125I
      epibatidine sites (low-affinity sites), 125I-A85380 and 125I-epibatidine sites
      are localized in part to dopaminergic terminals. In summary, these results show
      that alpha-conotoxinMII-sensitive sites are present in human striatum and that
      there are high- and low-affinity subtypes which are both decreased in Parkinson's
      disease.

PMID- 14720217
TI  - Phospholipase D2 modulates agonist-induced mu-opioid receptor desensitization and
      resensitization.
AB  - Receptor phosphorylation, arrestin binding, uncoupling from G protein and
      subsequent endocytosis have been implicated in G protein-coupled receptor
      desensitization after chronic agonist exposure. In search of proteins regulating
      the mu-opioid receptor endocytosis, we have recently established that activation
      of phospholipase D (PLD)2 is required for agonist-induced mu-opioid receptor
      endocytosis. In this study, we determined the effect of PLD2 activity on the
      desensitization and resensitization rate of the mu-opioid receptor. We clearly
      demonstrated that inhibition of PLD2-mediated phosphatidic acid formation by
      alcohol (1-butanol or ethanol) or overexpression of a dominant negative mutant of
      PLD2 prevented agonist-mediated endocytosis and resulted in a faster
      desensitization rate of the mu-opioid receptor after chronic (D-Ala2, Me Phe4,
      Glyol5)enkephalin treatment in human embryonic kidney 293 cells. Moreover,
      inhibition of PLD2 activity led to an impairment of the resensitization rate of
      the mu-opioid receptor. In summary, our data strongly suggest that PLD2 is a
      modulator of agonist-induced endocytosis, desensitization and resensitization of
      the mu-opioid receptor.

PMID- 14720218
TI  - Cathepsin B mRNA and protein expression following contusion spinal cord injury in
      rats.
AB  - We provide the first data that cathepsin B (Cath B), a lysosomal cysteine
      protease, is up-regulated following contusion-spinal cord injury (SCI). Following
      T12 laminectomy and moderate contusion, Cath B mRNA and protein expression
      profiles were examined from 2 to 168 h post-injury in rats using real-time PCR
      and immunoblots, respectively. Contusion injury significantly increased
      [mRNA]Cath B in the injury site and adjacent segments over sham injury levels.
      While the largest [mRNA]Cath B induction (20-fold over naive) was seen in the
      injury site, the caudal segment routinely yielded [mRNA]Cath B levels greater
      than 10-fold over naive. Interestingly, sham injury animals also experienced mRNA
      induction at several time points at the injury site and in segments rostral and
      caudal to the injury site. Contusion injury also significantly elevated levels of
      Cath B proenzyme protein (37 kDa) over sham injury in the injury site (48, 72 and
      168 h post-injury). Furthermore, significant protein increases of single and
      double chain Cath B (both active forms) occurred at the injury site at 72 and 168
      h post-injury. Similar significant increases in Cath B protein levels were seen
      in areas adjacent to the injury site. The induction of Cath B mRNA and protein
      expression following contusion injury is previously undescribed and suggests that
      Cath B may potentially be involved in the secondary injury cascade, perhaps for
      as long as 1 week post-injury.

PMID- 14720219
TI  - Improvement of embryonic dopaminergic neurone survival in culture and after
      grafting into the striatum of hemiparkinsonian rats by CEP-1347.
AB  - Transplantation of embryonic nigral tissue ameliorates functional deficiencies in
      Parkinson's disease (PD). A main constraint of neural grafting is the poor
      survival of dopaminergic neurones grafted into patients. Studies in rats
      indicated that many grafted neurones die by apoptosis. CEP-1347 is a mixed
      lineage-kinase (MLK) inhibitor with neuroprotective action in several in vitro
      and in vivo models of neuronal apoptosis. We studied the effect of CEP-1347 on
      the survival of embryonic rat dopaminergic neurones in culture, and after
      transplantation in hemiparkinsonian rats. CEP-1347 and the alternative MLK
      inhibitor CEP-11004 significantly increased the survival of dopaminergic neurones
      in primary cultures from rat ventral mesencephalon and in Mn2+-exposed PC12
      cells, a surrogate model of dopaminergic lethal stress. Moreover, combined
      treatment of the grafting cell suspension and the host animal with CEP-1347
      significantly improved the long-term survival of rat dopaminergic neurones
      transplanted into the striatum of hemiparkinsonian rats. Also, the protective
      effect of CEP-1347 resulted in an increase in total graft size and in enhanced
      fibre outgrowth. Thus, treatment with CEP-1347 improved dopaminergic cell
      survival under severe stress and might be useful to improve the positive outcome
      of transplantation therapy in PD and reduce the amount of human tissue required.

PMID- 14720220
TI  - NR2A induction and NMDA receptor-dependent neuronal death by neurotrophin-4/5 in
      cortical cell culture.
AB  - We have previously shown that prolonged exposure to neurotrophins induces
      oxidative neuronal death. In the present study, we further examined the cascades
      involved in neurotrophin-4/5 (NT-4/5)-induced neuronal death. Exposure of mature
      cortical cultures for 48 h to NT-4/5 induced neuronal death through TrkB
      activation. The NT-4/5-induced neuronal death was largely attenuated by addition
      of MK-801, indicating a critical role for NMDA receptors. Western blots revealed
      the induction of NR2A by NT-4/5. In addition, levels of phospho-NR2A and 2B
      increased, suggesting the upregulation of the NMDA receptor function. Whereas
      glutamate levels in the media changed little, levels of D-serine and L-glycine,
      co-agonists at NMDA receptors, increased significantly following NT-4/5
      treatment. Exposure to NT-4/5 resulted in the activation of Src and extracellular
      signal-regulated kinase-1/2 (Erk-1/2). Their inhibitors blocked NR2A induction
      and phosphorylation as well as neuronal death induced by NT-4/5. In addition, Egr
      1 was induced in an Src- and Erk-1/2-dependent manner. Anti-sense
      oligodeoxynucleotides to egr-1 attenuated NR2A induction as well as neuronal
      death. Although induction of NADPH oxidase and neuronal nitric oxide synthase
      (nNOS) contributes to NT-4/5-induced neuronal death, inhibition of their activity
      did not reduce NR2A induction. Conversely, blockade of NMDA receptors did not
      attenuate induction of NADPH oxidase or nNOS. These results indicate that two
      events are largely independent of each other. Our results demonstrate that the
      signaling cascade of TrkB leads to increase in NMDA receptor activity. Whereas
      this cascade may play an important role in the modulation of NMDA receptors in
      physiologic conditions, in the context of TrkB overactivation, it may contribute
      to neuronal death.

PMID- 14720221
TI  - Phosphorylation of extracellular-regulating kinase in NMDA receptor antagonist
      induced newly generated neurons in the adult rat dentate gyrus.
AB  - Neurogenesis in the adult brain is promoted by various stimulations. NMDA
      receptor blockade enhances neurogenesis in the hippocampal dentate gyrus. There
      is no agreed conclusion, however, as to whether newly generated neurons after
      NMDA receptor blockade obtain functional properties. We investigated the
      functional maturation of newly generated neurons after NMDA receptor blockade. In
      the dentate gyrus, 80% of newly generated cells differentiated into the phenotype
      of mature neurons at 29 days after the single intraperitoneal injection of an
      NMDA receptor antagonist MK-801. The number of newly generated neurons after MK
      801 treatment was significantly greater than that in the saline-treated group.
      The neurogenic basic helix-loop-helix transcription factor NeuroD protein in the
      dentate gyrus after MK-801 treatment was expressed transiently in proliferative
      cells, but not in mature neurons. To determine functional properties of newly
      generated neurons, we administered NMDA to the lateral ventricle. As an in vivo
      response, we assessed extracellular-regulating kinase (ERK) phosphorylation. The
      newly generated neurons showed ERK phosphorylation by NMDA administration as seen
      in surrounding mature neurons. The number of newly generated neurons, which
      responded to NMDA receptor stimulation, increased with time after MK-801
      treatment. The present study provides evidence that newly generated neurons in
      the adult hippocampus after NMDA receptor blockade acquire biochemical function
      in vivo.

PMID- 14720222
TI  - Homodimerization of adenosine A2A receptors: qualitative and quantitative
      assessment by fluorescence and bioluminescence energy transfer.
AB  - The results presented in this paper show that adenosine A2A receptor (A2AR) form
      homodimers and that homodimers but not monomers are the functional species at the
      cell surface. Fluorescence resonance energy transfer (FRET) and bioluminescence
      resonance energy transfer (BRET) techniques have been used to demonstrate in
      transfected HEK293 cells homodimerization of A2AR, which are heptaspanning
      membrane receptors with enriched expression in striatum. The existence of
      homodimers at the cell surface was demonstrated by time-resolved FRET. Although
      agonist activation of the receptor leads to the formation of receptor clusters,
      it did not affect the degree of A2AR-A2AR dimerization. Both monomers and dimers
      were detected by immunoblotting in cell extracts. However, cell surface
      biotinylation of proteins has made evident that more than 90% of the cell surface
      receptor is in its dimeric form. Thus, it seems that homodimers are the
      functional form of the receptor present on the plasma membrane. A deletion mutant
      version of the A2A receptor, lacking its C-terminal domain, was also able to form
      both monomeric and dimeric species when cell extracts from transfected cells were
      analyzed by immunoblotting. This suggests that the C-terminal tail does not
      participate in the dimerization. This is relevant as the C-terminal tail of A2AR
      is involved in heteromers formed by A2AR and dopamine D2 receptors. BRET ratios
      corresponding to A2AR-A2AR homodimers were higher than those encountered for
      heterodimers formed by A2AR and dopamine D2 receptors. As A2AR and dopamine D2
      receptors do indeed interact, these results indicate that A2AR homodimers are the
      functional species at the cell surface and that they coexist with A2AR/D2
      receptor heterodimers.

PMID- 14720223
TI  - Morphological and biochemical changes of neurofilaments in aged rat sciatic nerve
      axons.
AB  - We have made a detailed comparison of neurofilaments (NFs) in the axons of the
      sciatic nerves between young and aged rats. In young rats, NF density was similar
      between proximal and distal sciatic nerve, but it became higher in the proximal
      region of sciatic nerve of aged rats. In accordance with this morphological
      change, NF protein content decreased dramatically in the middle region of the
      sciatic nerves of aged rats. The ratio of NF-M to NF-H in aged rats was lower
      than that in young rats at the proximal region of sciatic nerves and further
      decreased in the distal region of sciatic nerve. We analyzed transcription and
      axonal transport of NF proteins in motor neurons in spinal cord which are the
      major constituents of sciatic nerve axons. Of the transcripts of the NF subunits,
      NF-M mRNA was particularly reduced in aged rats. Examination of slow axonal
      transport revealed that the transport rate for NF-M was slightly faster than that
      for NF-H in young rats, but slightly slower in aged rats. A decrease in both the
      synthesis and transport rate of NF-M with aging may contribute to the relative
      reduction in NF-M in the aged rat sciatic nerve. Although the relationship
      between NF packing and reduced NF-M is not clear at present, these changes in NFs
      may be associated with age-dependent axonal degeneration diseases.

PMID- 14720224
TI  - Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram
      positive bacterium Staphylococcus aureus.
AB  - Astrocytes play an important role in initiating and regulating CNS immune
      responses through the release of proinflammatory cytokines and chemokines. Here
      we demonstrate that primary astrocytes are capable of recognizing the Gram
      positive bacterium Staphylococcus aureus and its cell wall product peptidoglycan
      (PGN) and respond by producing numerous proinflammatory mediators including
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), macrophage
      inflammatory protein-1beta (MIP-1beta), MIP-2, and monocyte chemoattractant
      protein (MCP-1). Astrocytes have recently been shown to express Toll-like
      receptor 2 (TLR2), a pattern recognition receptor important for recognizing
      structural components of various Gram-positive bacteria, fungi, and protozoa.
      However, the functional significance of TLR2 in mediating astrocyte activation
      remains unknown. Primary astrocytes from TLR2 knockout mice were used to evaluate
      the role of TLR2 in astrocyte responses to S. aureus and PGN. The results
      demonstrate that TLR2 is essential for maximal proinflammatory cytokine and
      chemokine production, but not phagocytosis, in primary astrocytes following S.
      aureus and PGN exposure. In addition, both stimuli led to a significant increase
      in TLR2 mRNA expression in wild-type astrocytes as assessed by real-time
      quantitative RT-PCR. These findings suggest that astrocytes may play a key role
      in the initial antibacterial immune response in the CNS through engagement of
      TLR2.

PMID- 14720225
TI  - Molecular constituents of the postsynaptic density fraction revealed by proteomic
      analysis using multidimensional liquid chromatography-tandem mass spectrometry.
AB  - Protein constituents of the postsynaptic density (PSD) fraction were analysed
      using an integrated liquid chromatography (LC)-based protein identification
      system, which was constructed by coupling microscale two-dimensional liquid
      chromatography (2DLC) with electrospray ionization (ESI) tandem mass spectrometry
      (MS/MS) and an automated data analysis system. The PSD fraction prepared from rat
      forebrain was solubilized in 6 m guanidium hydrochloride, and the proteins were
      digested with trypsin after S-carbamoylmethylation under reducing conditions. The
      tryptic peptide mixture was then analysed with the 2DLC-MS/MS system in a data
      dependent mode, and the resultant spectral data were automatically processed to
      search a genome sequence database for protein identification. In triplicate
      analyses, the system allowed assignments of 5264 peptides, which could finally be
      attributed to 492 proteins. The PSD contained various proteins involved in
      signalling transduction, including receptors, ion channel proteins, protein
      kinases and phosphatases, G-protein and related proteins, scaffold proteins, and
      adaptor proteins. Structural proteins, including membrane proteins involved in
      cell adhesion and cell-cell interaction, proteins involved in endocytosis, motor
      proteins, and cytoskeletal proteins were also abundant. These results provide
      basic data on a major protein set associated with the PSD and a basis for future
      functional studies of this important neural machinery.

PMID- 14720226
TI  - From archetypes to reflective function.
AB  - This paper challenges the view that mental contents can be innate and offers
      instead a developmental model in which mental contents emerge from the
      interaction of genes, brain and environment. Some key steps on this developmental
      pathway are traced, such as the formation of image schemas. The processes by
      which mental contents are evaluated and organized are described, notably those of
      perceptual analysis, representational re-description and appraisal. Jung's
      concept of the transcendent function is seen to have certain crucial features in
      common with each of these processes. The emergence of the capacity to symbolize
      is explored in relation to these concepts and it is suggested that the pinnacle
      of this capacity is achieved in the emergence of reflective function, in which
      mind is represented to itself.

PMID- 14720227
TI  - Symbols and self preservation in severe disturbance.
AB  - The author considers a particular way in which symbolic functioning and the sense
      of self fail in certain cases of severe disturbance. When containment of the
      infant fails, the experience is a violent one. If the infant is projected into by
      an 'invasive object', the infant can incorporate this experience both as a bodily
      and a proto-mental registration. The experience then remains within the psyche
      soma and subsequent development is built 'around' the consequences of the trauma.
      Clinical illustrations are provided to demonstrate this phenomenon in the
      analytic setting.

PMID- 14720228
TI  - The universe of our concerns: the human as person in the praxis of analysis.
AB  - Since its inception, psychoanalysts and analytical psychologists have used the
      reductionistic methods of science to explain both human development and analytic
      practice. The most recent iteration of this tendency uses attachment as the
      explanatory principle. This disposition has created theories that understand the
      human solely as an organism. While this is a satisfactory way to view human
      development, it is not appropriate for the practice of analysis. In this context,
      the human must be viewed as a person that is explicable in his/her own terms.
      Interpretation based on reductionism eliminates personhood. Humans appear as
      persons in 'the feeling of what happens' or of 'being there', and, on the basis
      of this experience, develop stories in which their personhood evolves. The
      psychoanalytic, philosophical and neuro-scientific basis for this view of the
      human as person is discussed, and its relevance for analytic practice is
      considered.

PMID- 14720229
TI  - The explicit and implicit dance in psychoanalytic change.
AB  - How the implicit/non-declarative and explicit/declarative cognitive domains
      interact is centrally important in the consideration of effecting change within
      the psychoanalytic arena. Stern et al. (1998) declare that long-lasting change
      occurs in the domain of implicit relational knowledge. In the view of this
      author, the implicit and explicit domains are intricately intertwined in an
      interactive dance within a psychoanalytic process. The author views that a spirit
      of inquiry (Lichtenberg, Lachmann & Fosshage 2002) serves as the foundation of
      the psychoanalytic process. Analyst and patient strive to explore, understand and
      communicate and, thereby, create a 'spirit' of interaction that contributes,
      through gradual incremental learning, to new implicit relational knowledge. This
      spirit, as part of the implicit relational interaction, is a cornerstone of the
      analytic relationship. The 'inquiry' more directly brings explicit/declarative
      processing to the foreground in the joint attempt to explore and understand. The
      spirit of inquiry in the psychoanalytic arena highlights both the
      autobiographical scenarios of the explicit memory system and the mental models of
      the implicit memory system as each contributes to a sense of self, other, and
      self with other. This process facilitates the extrication and suspension of the
      old models, so that new models based on current relational experience can be
      gradually integrated into both memory systems for lasting change.

PMID- 14720230
TI  - What are symbols symbols of? Situated action, mythological bootstrapping and the
      emergence of the Self.
AB  - This paper addresses the question of how symbols should be understood in
      analytical psychology and psychoanalysis. The point of view examined focuses on
      the recent turn to more cognitive and developmental models in both disciplines
      and briefly reviews and critiques the evolutionary and cognitive arguments. The
      paper then presents an argument based on dynamic systems theory in which no pre
      existing template or structure for either mind or behaviour is assumed. Within
      the dynamic systems model the Self is viewed as an emergent phenomenon deriving
      from the dynamic patterns existing in a complex system that includes the
      physiological characteristics of the infant, the intentional attributions of the
      caregiver and the cultural or symbolic resources that constitute the environment.
      The symbol can then be seen as a discrete, and in important ways an autonomous,
      element in the dynamic system. Conclusions are drawn for further research into
      the nature of the symbol with implications for both theory and practice in
      analytical psychology and psychoanalysis.

PMID- 14720231
TI  - The mind-brain relationship: the emergent self.
AB  - This paper explores the mind-brain relationship, using insights from contemporary
      neuroscience. It seeks to investigate how our brains become who we are, how
      subjective experience arises. In order to do this some explanation is given of
      the basic concepts of how the brain produces our subjective mental life. Current
      neuropsychological and neurobiological understanding of early brain development,
      memory, emotion and consciousness are explored. There is also an attempt at
      mapping the mind-brain-self relationship from a uniquely Jungian perspective.
      Clinical material is included in order to show the relevance of these insights to
      our work in the consulting room, arguing the value of the affect-regulating,
      relational aspects of the analytic dyad that forge new neural pathways through
      emotional connection. Such experience forms the emotional scaffolding necessary
      for the emergence of reflective function.

PMID- 14720232
TI  - From aggressiveness to creativity.
AB  - Psychology has a long tradition of considering human creativity as a distinct
      human characteristic and a special kind of human activity. After explaining the
      key motives for such an attitude, the author discusses those forms of healthy
      aggressiveness that stand out as necessary and constitutive elements of the
      creative process. Taking the well-known statement of C. G. Jung's 'The person who
      does not build (create), will demolish and destroy' as a starting point, the
      author compares the basic premises for understanding the process of human
      creativity, at the same time drawing on Freud's psychology of the individual and
      Jung's principle of the collective unconscious as well as his notion of
      'complexes'. In doing so, the author somewhat boldly paraphrases Jung's dictum:
      'In order to be creative, rather than just constructive, one must occasionally
      also destroy'. With reference to Wallas, Taylor and Neumann (Wallas 1926; Taylor
      1959;;Neumann 2001), the author goes on to explore those concepts which help us
      to investigate the phenomenon of human creativity, drawing distinctions between
      emergent, expressive, productive, inventive and innovative creativity. The second
      part of the article discusses the importance of intelligence, originality,
      nonconformity, subversiveness and free-mindedness for the creative process of
      human beings. The author concludes with a further explanation of Erich Neumann's
      argument that human creativity cannot be understood solely as a result of
      sociogenetic factors, and argues that it is only by taking into consideration
      Jung's perception of creativity that a global ontological understanding of these
      processes can be achieved.

PMID- 14720238
TI  - Editor's note: analysis of papers published in JAN in 2002.

PMID- 14720240
TI  - Pain assessment in intellectually disabled people: non-verbal indicators.
AB  - BACKGROUND: Although important progress has been made during the past decade,
      research on pain in people with intellectual disabilities is still scarce. Pain
      assessment in people with intellectual disabilities is a frequent and difficult
      problem, especially for nurses working with people with intellectual disabilities
      on a daily basis. Gathering more information about pain in people with
      intellectual disabilities is of major importance and relevance for nursing, and
      adds to the developing body of knowledge. OBJECTIVE: To investigate the nature
      and relative importance of non-verbal indicators used by nurses to assess pain in
      people with a severe or profound intellectual disability. METHODS: A
      questionnaire consisting of 158 indicators of pain was used. A total of 135
      nurses from nine institutions specializing in the care of people with
      intellectual disability were asked to rate each indicator on a scale of 1-10 to
      show which non-verbal expressions they considered important in diagnosing pain.
      RESULTS: A total of 109 nurses responded. All 158 indicators were mentioned as
      being important to indicate pain. All except four had a range of 9. Seven
      (moaning during manipulation, crying during manipulation, painful facial
      expression during manipulation, swelling, screaming during manipulation, not
      using (affected) body part, and moving the body in a specific way of behaving)
      were reported as 'very important' by more than 50% of nurses. The lowest score
      (median 5.5; minimum 1, maximum 10) was given to the indicator 'waving arm
      movements'. The pain of people with severe intellectual disability appeared to be
      assessed differently from that of people with profound intellectual disability.
      Indicators belonging to the 'physiological' category scored relatively higher in
      the group of nurses specializing in profound disability. In contrast, indicators
      belonging to the 'social-emotional' category were scored relatively higher by
      nurses specializing in severe disability. CONCLUSION: Nurses used a wide range of
      indicators to assess pain in people with intellectual disability. Functional
      abilities and level of disability seem to influence the indicators used.

PMID- 14720241
TI  - Use of physical restraints with cognitively impaired nursing home residents.
AB  - AIM: The aim of the study was to examine the prevalence of physical restraint use
      in cognitively impaired nursing home residents, the manner in which restraints
      are used, reasons for using them, and relationships between residents'
      characteristics and use of physical restraints. METHODS: A point prevalence study
      was conducted on the use of physical restraints among all residents cared for in
      two Dutch nursing homes and one nursing home unit (n = 265). Data about the
      nursing home residents and the use of restraints were collected by means of a
      questionnaire, which was filled in by the nurses. The response rate was 98%. The
      mean age of residents was 81 years (sd = 8.6), 74% of whom were female. RESULTS:
      One or more restraints were used with 49% of the residents. The most frequently
      used physical restraints were bed rails, a waist belt, and a chair with a table.
      In almost all situations (90%), residents were continuously restrained and
      restraints were used for longer than 3 months. The most common reason (90%) for
      use of restraints was to prevent falls. Logistic regression analysis revealed
      that use of restraints was highly associated with poor mobility, care dependency
      and risk of falling in the opinion of nursing staff. CONCLUSIONS: The results of
      this study are comparable with those of other studies. However, since recent
      studies have reported that physical restraints are inadequate to prevent falls,
      recommendations are made to re-evaluate critically the use of restraints and to
      conduct future research into a responsible and safe way of decreasing the use of
      physical restraints.

PMID- 14720242
TI  - Effectiveness of acupressure in improving dyspnoea in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) suffer
      from dyspnoea in their daily life and this may be increased by anxiety.
      Acupressure may promote relaxation and relieve dyspnoea. Thus, it is appropriate
      to explore the effectiveness of acupressure on dyspnoea in patients with COPD.
      AIMS: To compare outcomes of acupressure using sham acupoints on different
      meridians and ganglionic sections with that using true acupoints, in patients
      with COPD who are living at home. METHODS: Patients diagnosed with COPD were
      selected from a medical centre and three regional hospitals in Taipei. A
      randomized block experimental design was used. Using age, sex, pulmonary
      function, smoking, and steroid use as matching factors, 44 patients were randomly
      assigned either to a true acupoint acupressure or a sham group. The true acupoint
      acupressure group received a programme to decrease dyspnoea. Those in the sham
      group received acupressure using sham pressure points. Both acupressure
      programmes consisted of five sessions per week lasting 16 minutes per session,
      extending over 4 weeks for a total of 20 sessions. Before acupressure was
      initiated and at the conclusion of the 20th session, the Pulmonary Functional
      Status and Dyspnoea Questionnaire-modified scale and the Spielberger State
      Anxiety scale were administered, and a 6-minute walking distance test was
      performed. Physiological indicators of oxygen saturation and respiratory rate
      were measured before and after every session. RESULTS: The results of this study
      showed that the pulmonary function and dyspnoea scores, 6-minute walking distance
      measurements, state anxiety scale scores, and physiological indicators of the
      true acupoint acupressure group improved significantly compared with those of the
      sham group. CONCLUSIONS: The findings suggest that acupressure can be used as a
      nursing intervention to improve dyspnoea in patients with COPD.

PMID- 14720243
TI  - Infant feeding attitudes of expectant parents: breastfeeding and formula feeding.
AB  - BACKGROUND: Research has indicated that parental attitudes are strong predictors
      of choice of infant feeding. Identification and understanding of the infant
      feeding attitudes of mothers and their social networks should be an early step in
      the design and implementation of breastfeeding interventions. AIM: To compare the
      infant feeding attitudes of parents of breastfed infants with those of parents of
      formula fed infants. METHODS: A survey was carried out with a convenience sample
      of pregnant women (gestational age 8-12 weeks) attending three maternity clinics
      in Scotland in 2000. Expectant mothers and their partners (n = 108 couples)
      completed the 17 item Iowa Infant Feeding Attitude Scale. Demographic information
      was collected by face-to-face interview and the method of feeding at discharge
      from hospital was obtained from medical records. RESULTS: Parents of breastfed
      infants had more positive attitudes towards breastfeeding than parents of formula
      fed infants, and were more knowledgeable about the health benefits and
      nutritional superiority of breastfeeding. Fathers of both breastfed and formula
      fed infants were more likely than their partners to disapprove of women
      breastfeeding in public. Parents considered their chosen method of feeding to be
      the more convenient alternative. Mothers of formula fed infants were more likely
      to think that women who occasionally drink alcohol should not breastfeed.
      CONCLUSION: Parents of formula fed infants had several misconceptions about
      breastfeeding. Use of the Iowa Infant Feeding Attitude Scale could help health
      professionals identify and address these in infant feeding discussions in the
      early antenatal period. Efforts should be made to include fathers in these infant
      feeding discussions.

PMID- 14720244
TI  - Nursing home care: changes after supervision.
AB  - BACKGROUND: An intervention project was conducted in three nursing home wards in
      Sweden. Most patients had severe dementia. The intervention consisted of
      supervision for individualized and documented nursing care, based on
      multidimensional assessment. AIM: To illuminate changes in carers' approach after
      the intervention. METHODS: Several data collections were conducted across the
      intervention and consisted of nursing documentation, patient life stories as told
      by carers, video recorded interactions, stimulated recall interviews and a
      questionnaire. Both quantitative and qualitative methods were used in the
      analyses. FINDINGS: The findings from the different methods mirrored each other
      and added to the credibility of the intervention. Communicated knowledge about
      patients improved in nursing documentation and also as told by carers. Carers
      were differently skilled in managing the complexity of nursing care situations
      before as well as after the intervention, but the intervention contributed to
      developing carers in 'confirming nursing care'. They also improved in their
      ability to verbalize reflections about their everyday life with patients with
      dementia. CONCLUSION: Supervision made it possible for carers to share their
      lived experiences about their day-to-day life with patients, which could promote
      personal and professional development and thus improve care quality. It also
      appeared that a detailed assessment tool used as part of the nursing process
      contributed to seeing a patient as a real person behind a dementia surface.

PMID- 14720245
TI  - Nurses' views of using computerized decision support software in NHS Direct.
AB  - BACKGROUND: Nurses working in NHS Direct, the 24-hour telephone advice line in
      England, use computerized decision support software to recommend to callers the
      most appropriate service to contact, or to advise on self-care. AIMS: To explore
      nurses' views of their roles and the computerized decision support software in
      NHS Direct. METHODS: Qualitative analysis of semi-structured interviews with 24
      NHS Direct nurses in 12 sites. FINDINGS: Nurses described both the software and
      themselves as essential to the clinical decision-making process. The software
      acted as safety net, provider of consistency, and provider of script, and was
      relied upon more when nurses did not have clinical knowledge relevant to the
      call. The nurse handled problems not covered by the software, probed patients for
      the appropriate information to enter into the software, and interpreted software
      recommendations in the light of contextual information which the software was
      unable to use. Nurses described a dual process of decision-making, with the nurse
      as active decision maker looking for consensus with the software recommendation
      and ready to override recommendations made by the software if necessary. However,
      nurses' accounts of the software as a guide, prompt or support did not fully
      acknowledge the power of the software, which they are required to use, and the
      recommendation of which they are required to follow under some management
      policies. Over time, the influence of nurse and software merges as nurses
      internalize the software script as their own knowledge, and navigate the software
      to produce recommendations that they feel are most appropriate. CONCLUSIONS: The
      nurse and the software have distinct roles in NHS Direct, although the effect of
      each on the clinical decision-making process may be difficult to determine in
      practice.

PMID- 14720246
TI  - Negotiating multiple roles: link teachers in clinical nursing practice.
AB  - BACKGROUND: The background to this study was a concern about the teacher's role
      in clinical practice. Experience suggested that teachers believed that their role
      in practice was important but that there were significant forces which impeded
      their ability to move with ease between education and practice. A discrepancy
      between previous research findings and theoretical discussions, and the reality
      experienced by teachers, led to the adoption of grounded theory as a way of
      exploring uncertainties in the situation. METHOD: Data were gathered over a
      period of 7 years and involved 28 in-depth interviews with nurses with a range of
      educational roles, employed in educational institutions and practice settings in
      inner city and provincial areas in the South of England. FINDINGS: The data
      revealed four categories, 'gaining access', 'negotiating credibility', 'being
      effective' and the core category 'negotiating multiple roles'. The core category
      is addressed in this article. Experiences of moving from a position of clinical
      practitioner to link teacher involved: 'disassembling the self' through leaving
      behind old identities; 'reconstructing the self' through clarifying new ways of
      being; and, finally, 'realizing the self' through reciprocal interpersonal
      activity with students, educational and nursing colleagues. CONCLUSIONS: It is
      inevitable that an individual with a remit for change entering an established
      social group will experience difficulties in establishing their role. It is also
      clear that an individual who changes their role within a group to reflect
      behaviours not congruent with the primary activity in that setting will
      experience dimensions of social exclusion. Further work needs to address how
      educational roles can make a significant impact on the everyday lives of students
      and nurses working in practice. The findings of this study are as relevant for
      the new roles of practice educator, clinical facilitator and practice placement
      co-ordinator as they are for link teachers and lecturer practitioners. Several
      suggestions are made to improve links with practice.

PMID- 14720247
TI  - Mature women's experiences of preregistration nurse education.
AB  - BACKGROUND: The government of the United Kingdom is encouraging more flexible
      recruitment strategies to overcome the shortage of qualified nurses. Mature women
      returning to education, often after completing their families, are a major
      target, but there has been little evaluation of their experiences as higher
      education students of nursing. AIM: The aim of the study was to follow-up a
      previous quantitative study of mature women students' outcomes on preregistration
      diploma courses in order to gain a deeper understanding of their experiences, and
      consider ways in which their needs might be addressed. METHODS: Five focus groups
      were conducted in one higher education institution, and data were analysed using
      thematic analysis, assisted by the 'spike' feature of Word for Windows. FINDINGS:
      Three major themes were identified: 'Didn't know what to expect', 'Reality shock'
      and 'Learning the game'. Subthemes of 'Learning the game' were 'Academic study',
      'Practice placements and shift work', 'Managing the effect of course workload on
      domestic roles', 'Personal growth and changing relationships', and 'Support
      systems and friendships'. CONCLUSIONS: The findings are discussed in relation to
      reports of women's experiences in higher education in general. We conclude that
      the situation and needs of mature women preregistration nursing students are such
      that fundamental curriculum redesign is needed so that they can participate in
      higher education in ways that allow integration of their family and student
      lives, and permit them to benefit from the higher education experience in the
      same ways as younger students. The study is limited by its local nature, but the
      findings mirror those of other work, giving reassurance of its wider
      applicability. Recommendations are made for changes in the philosophy and
      organization of future programmes to improve their appropriateness and
      acceptability to mature women nursing students.

PMID- 14720248
TI  - Spirituality and child development: a concept analysis.
AB  - BACKGROUND: If children are to be given the opportunity to develop to their full
      potential, fostering spiritual growth must be part of the process of caring for
      them. However, the meaningful application of spiritual care in everyday practice
      is fraught with difficulties. In addition to a lack of understanding of the term
      itself and of the expression of spirituality, in child health these difficulties
      are further compounded by the stage of a child's development. AIM: The aims of
      this paper are to explore spiritual awareness in children by providing examples
      of the expression of spiritual beliefs in relation to the developmental stage of
      the child, and to identify the implications of the findings for clinical
      practice. METHOD: A model of concept development, using the cyclical process of
      'significance', 'use' and 'application' was applied, and formed the philosophical
      underpinnings for the paper. This framework is particularly relevant to child
      health, as there is little evidence to draw on, particularly in relation to a
      child's spiritual needs. FINDINGS: Five primary research papers which met the
      inclusion criteria were reviewed, and provided examples of spiritual beliefs and
      their manifestations in children. The examples highlighted the diversity and
      complexity of children's thinking. CONCLUSIONS AND RECOMMENDATIONS: Health care
      professionals working with children should receive education about the spiritual
      needs of children. Assessment tools should be developed to facilitate detailed
      assessment of children's spiritual needs. Professionals need to listen to and
      communicate with children at different stages of development if spiritual
      distress is to be identified. Families' health care beliefs should be respected
      and considered when planning care.

PMID- 14720249
TI  - Ethical practice in nursing: working the in-betweens.
AB  - BACKGROUND: While contemporary ethical theory is of tremendous value to nursing,
      the extent to which such theory has been informed by the concerns and practices
      of nurses has been limited. PURPOSE: With a view to complementing extant ethical
      theory, a study was undertaken to explore, from the perspective of nurses, the
      meaning of ethics and the enactment of ethical practice in nursing. DESIGN AND
      METHODS: Located in the interpretive/constructivist paradigm, using an emergent
      design, this inquiry employed focus groups to collect the data. Eighty-seven
      nurses from a wide range of practice settings were interviewed in 19 focus groups
      of three to nine nurses each. FINDINGS: The nurses described ethics in their
      practice as both a way of being and a process of enactment. They described
      drawing on a wide range of sources of moral knowledge in a dynamic process of
      developing awareness of themselves as moral agents. Enacting moral agency
      involved working in a shifting moral context, and working in-between their own
      values and those of the organizations in which they worked, in-between their own
      values and those of others, and in-between competing values and interests.
      CONCLUSIONS: Analysis of the experiences and concerns of the nurses offered new
      understanding of ethics in nursing and direction for the development of ethical
      theory pertinent to nursing practice.

PMID- 14720250
TI  - Nurses' autonomy: influence of nurse managers' actions.
AB  - BACKGROUND: Autonomy plays an important part in nurses' job satisfaction and
      retention, but the literature shows that they are often dissatisfied with this
      aspect and want better working conditions and greater autonomy in decision
      making. AIMS: The aim of this study was to examine the role that nurse managers
      have in enhancing hospital staff nurses' autonomy. METHODS: The study used a
      comparative descriptive survey design. Data collection took place over the
      Internet through the use of selective listservs in the United States of America
      (USA), Canada, and the United Kingdom. Of the 317 hospital nurses participating,
      264 (83.3%) were from the USA. Differences relating to nurses, nurse managers,
      and hospital settings were controlled in the analysis. RESULTS: Nurses were more
      autonomous in making patient care decisions than unit operational decisions, and
      they perceived their autonomy to be at a moderate level. Those who were
      autonomous in patient care decision-making were also likely to be autonomous in
      unit operation decision-making. Nurse managers' actions had a strong relationship
      with nurses' autonomy in deciding on patient care and unit operation decisions,
      and with total autonomy. The three important variables that were reported by
      staff nurses to increase their autonomy were supportive management, education and
      experience. The three most important factors that were reported to decrease
      nurses' autonomy were autocratic management, doctors and workload. DISCUSSION:
      Technical issues such as the availability of listservs, valid e-mails, viruses,
      and familiarity with the Internet and its applications were the major limitations
      of this study. Nurses' autonomy over patient care and unit operations decisions
      needs to be enhanced, and nurse managers should promote this. Similarly, there is
      a role for nurse education, both in preregistration programmes and in continuing
      education for managers. Further research needs to explore the barriers that
      nurses face in autonomous decision-making and how nurses' participation in unit
      operational decisions can be promoted. CONCLUSIONS: Hospital staff nurses have
      moderate autonomy which could be increased by more effective support from nurse
      managers. The use of electronic questionnaires is a promising data collection
      method.

PMID- 14720251
TI  - Response to: Henery N. (2003) Constructions of spirituality in contemporary
      nursing theory. Journal of Advanced Nursing 42, 550-557.

PMID- 14720254
TI  - ADAM33 gene: confirming a gene without linkage.

PMID- 14720255
TI  - Cytotoxic T lymphocyte antigen 4 polymorphisms and allergic asthma.

PMID- 14720256
TI  - Direct or indirect stimuli for bronchial challenge testing: what is the relevance
      for asthma epidemiology?

PMID- 14720257
TI  - Role of T cell co-stimulation in murine models of allergic asthma.

PMID- 14720258
TI  - Asthma is associated with single-nucleotide polymorphisms in ADAM33.
AB  - BACKGROUND: The ADAM33 gene has recently been associated with asthma and
      bronchial hyper-reactivity. It codes for a disintegrin and metalloproteinase that
      triggers intra- and extracellular signalling by protein shedding. OBJECTIVE: We
      examined whether polymorphisms in ADAM33 are associated with asthma and related
      traits in two German populations. METHODS: We genotyped 15 intragenic single
      nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry of allele-specific primer extension products.
      The transmission disequilibrium test was used for association analysis in the
      German asthma family study. Additionally, we tested for association of these SNPs
      in a case-control sample from the European Community Respiratory Health Study
      using Armitage's trend test. RESULTS: In both studies, we found SNPs that were
      significantly associated with asthma and related traits. In the family study,
      significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the
      lowest P-value for F+1, P=0.005). Remarkably, this association is seen even in
      the absence of linkage with two microsatellite markers from a previous genome
      scan either 3.1 million bases (Mb) up- or 5.6 Mb downstream. In the case-control
      study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these
      SNPs overlapped with those found to be associated with elevated total IgE levels
      and bronchial hyper-responsiveness. CONCLUSION: This study replicates the
      recently published association between asthma and ADAM33 gene variants. However,
      most of the associated SNPs were at non-identical positions in the German, UK and
      US samples. As linkage disequilibrium is high among the tested SNPs, and there is
      no known functional polymorphism, either not-tested variants in ADAM33, unknown
      regulatory elements or a gene in close proximity is responsible for this
      association.

PMID- 14720259
TI  - Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender
      discrepancy of serum total IgE levels and allergic diseases.
AB  - BACKGROUND: A variety of genes are related to allergic disorders in different
      ethnic populations. The genetic basis for the gender discrepancy of allergic
      diseases remains to be determined. OBJECTIVE: This study was conducted to
      investigate whether IL-4 promoter (-590 C/T) and cytotoxic T lymphocyte antigen 4
      (CTLA-4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of
      total IgE levels and allergic diseases in a Chinese population. METHODS: A total
      of 1333 participants aged 19-49 years were enrolled in this study. Allergic
      diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis
      in conjunction with detectable specific IgE in the blood. Polymorphisms of IL-4
      promoter (-590) and CTLA-4 (+49) were determined by restriction fragment length
      polymorphism. RESULTS: Males or females with allergic diseases had higher total
      IgE levels than those without (P=0.000). Females with the A/A genotype in the
      CTLA-4 (+49) position had significantly higher total IgE levels than those with
      A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1
      vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males
      with different genotypes in the CTLA-4 (+49) position exhibited no difference in
      the total IgE levels. Females with allergic rhinitis had a significantly higher
      frequency of the A/A genotype in the CTLA-4 (+49) polymorphism than those without
      atopic diseases (P=0.016). In contrast, males with and without allergic disorders
      exhibited no significant difference in the CTLA-4 (+49) polymorphisms (P>0.05).
      The IL-4 promoter (-590) polymorphisms, however, had no correlation with the
      total IgE levels or allergic diseases in either females or males. CONCLUSION: In
      females only, the CTLA-4 (+49), but not the IL-4 promoter (-590), polymorphism
      was significantly associated with elevation of total IgE levels and allergic
      rhinitis. Here, we have, for the first time, demonstrated a gender-linked genetic
      relationship with allergic disease.

PMID- 14720260
TI  - Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from
      farming and non-farming environments. A nationwide study over three decades.
AB  - BACKGROUND: Asthma and allergies are less common in children who have been raised
      in farming environments. OBJECTIVES: To assess whether children who grow up in a
      farming environment have been protected against the general increase in atopic
      disorders in Sweden and whether other rural environments could also be
      protective. METHOD: Linkage at an individual level of three national registers in
      Sweden: The Swedish Military Service Conscription Register (MSCR), the Register
      of the Total Population (RTP) and the Population and Housing Censuses (PHC).
      Asthma, allergic rhinitis and eczema at conscription were analysed in relation to
      area of residence, parental occupation, maternal age, family size and being the
      first born for 1 309 652 male conscripts in three successive cohorts born between
      1952 and 1981. RESULTS: Allergic rhinitis and eczema displayed a continuous
      increase throughout the study period, whereas the rise in asthma mainly occurred
      in conscripts born after 1961. Farming environments and rural living already
      provided protection from allergic rhinitis in conscripts born during the 1950s,
      but the protective effect was greater in later cohorts. An inverse association
      was observed between farm living and asthma, but mainly in conscripts born after
      1970. The adjusted risk ratios for asthma in conscripts from farming vs. non
      farming families were 1.00 (95% CI 0.93-1.07), 0.94 (95% CI 0.88-1.01) and 0.85
      (95% CI 0.79-0.91) in conscripts born in 1952-1961, 1962-1971 and 1972-1981,
      respectively. Rural living per se had no effect on the occurrence of asthma.
      Eczema was less common in rural areas, but the time trend was similar in urban
      and rural areas. CONCLUSIONS: Our findings suggest that environmental changes
      affecting the whole of society have promoted an increase in asthma, allergic
      rhinitis and eczema in both farming and non-farming environments. A lower risk of
      allergic rhinitis in conscripts whose parents were involved in farming was
      observed in all birth cohorts, whereas the protective effect of growing up on a
      farm on the risk of asthma appears to be a fairly recent phenomenon.

PMID- 14720261
TI  - Prenatal and early postnatal environments are significant predictors of total
      immunoglobulin E concentration in Filipino adolescents.
AB  - BACKGROUND: Recent evidence suggests that atopic disease may in part be mediated
      by fetal growth, as well as exposure to infectious disease early in life. Few
      studies have been able to evaluate these associations simultaneously, or to
      investigate prospectively the long-term effects of early environments while
      adequately controlling for potentially confounding variables. OBJECTIVE: To
      examine how prenatal growth and infectious disease in infancy are related to
      total IgE production in adolescence. METHODS: Ninety-nine adolescents (aged 14-15
      years) were selected from a larger cohort study according to the following
      criteria: full-term birth, currently healthy, and small-for-gestational age
      (N=53) or appropriate-for-gestational age (N=46). Plasma total IgE was measured
      with ELISA, and analysed in relation to anthropometric, nutritional, and
      environmental quality data collected prospectively beginning in the third
      trimester prior to birth. RESULTS: Each episode of infectious morbidity recorded
      at bimonthly intervals in the first 6 months of life was associated with a 0.12
      log IU/mL reduction in total IgE in adolescence (P=0.004). Prenatal
      undernutrition was associated with increased adolescent IgE, but only under
      conditions of an unsanitary household environment (P=0.002). Each additional
      kilogram gained per month in the first 6 months of life was associated with an
      increase in adolescent IgE of 0.74 log IU/mL (P=0.03). Each quartile increase in
      weekly household income at the time of blood sampling was associated with a 0.10
      log IU/mL reduction in total IgE (P=0.02). CONCLUSION: Infectious disease in
      infancy, as well as interactions between prenatal and postnatal environments,
      appear to have long-term effects on adolescent total IgE production. Future
      research should investigate the mechanisms behind these effects, and their
      implications for symptoms of atopic disease.

PMID- 14720262
TI  - Comparative prevalence of sensitization to common animal, plant and mould
      allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis
      living in a tropical environment.
AB  - BACKGROUND AND OBJECTIVES: Current information suggests that the expression of
      allergic diseases is determined by the exposure and nature of the allergen. The
      objectives of the present study were to determine if the nature of allergenic
      exposition to animal, plant or fungal allergens influenced the clinical
      manifestations of atopic dermatitis (AD), allergic rhinitis (AR) or asthma (AS)
      in patients living in a tropical environment. The prevalence and degree of
      sensitization to these allergens were analysed by age and gender. SUBJECTS AND
      METHODS: A total of 1496 atopic cases, grouped according to the primary diagnosis
      of AD or AR or AS, were skin tested using a standardized allergen panel.
      Participants were categorized by age groups. The atopic index (AI) and mean weal
      diameter (MWD) as well as the prevalence of positive skin tests were determined
      for each of the patient groups and compared by age groups. RESULTS: The
      prevalence of atopy as well as the AI and the MWD peaked at 6-15 years of age and
      declined thereafter. In all the patients tested, the prevalence of sensitization
      was, in decreasing order; dust mites 94.3%, cockroach 41.5%, pets 31.5%, plant
      allergens 31.1% and fungal 19.4%. Eight hundred and ninety-three atopic patients
      were exclusively sensitized only to animal allergens. Of these, 38.4% had AD,
      31.3% had AR and 30.5% with AS. CONCLUSION: These data demonstrate that for
      patients with AD, AR and AS living in a tropical environment, the prevalence of
      positive skin reactions to animal allergens is highest followed by plant and
      fungal allergens. We did not observe any association between the type of allergen
      and clinical manifestations. The index of atopy was similar for both sexes. The
      prevalence and degree of sensitization were shown to peak in young adults
      independent of the allergen in AD and AR patients.

PMID- 14720263
TI  - Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy,
      pulmonary function, and high-resolution computed tomography lung densitometry in
      elderly patients with asthma.
AB  - BACKGROUND: Smoking is the most important cause of chronic obstructive pulmonary
      disease (COPD). However, the influence of cigarette smoking on the pathogenesis
      of asthma in the elderly remains controversial. This study attempted to clarify
      the influence of cigarette smoking on elderly asthmatics. METHODS: Forty-eight
      asthmatics over 70 years old (25 ex-smokers and 23 never-smokers) and 20 patients
      with COPD over 70 years old (all ex-smokers) were studied to determine the
      influence of cigarette smoking on IgE-mediated allergy (total IgE, IgE antibodies
      against inhalant allergens, bronchial hyper-responsiveness (BHR), generation of
      leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung
      showing attenuation values less than -950 Hounsfield units (RA950) on high
      resolution computed tomography scans. RESULTS: The incidence of positive IgE
      antibodies against inhalant allergens, BHR, and the generation of leukotriene B4
      (LTB4) by leucocytes were significantly increased in patients with a history of
      smoking compared with those without. Residual volume (%RV) was significantly
      increased, and diffusing capacity for carbon monoxide was significantly decreased
      in ex-smokers with asthma and COPD compared with never-smokers with asthma.
      Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were
      significantly larger in asthmatics with a smoking history than in those without,
      and in COPD patients than in asthmatics. CONCLUSION: Cigarette smoking enhances
      the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in
      elderly asthmatics. Increased hyper-inflation or emphysematous changes of the
      lungs expressed by increased RA950, closely related to %RV, was more frequently
      observed in ex-smokers compared with never-smokers.

PMID- 14720264
TI  - Eosinophilia in nasal polyposis: its objective quantification and clinical
      relevance.
AB  - BACKGROUND: Eosinophilia within nasal polyps is often taken as a criterion for
      adjuvant medical treatment postoperatively such as topical steroids. OBJECTIVE:
      This study was performed in order to validate a new technique for objective
      quantification of eosinophilia by using laser scanning cytometry (LSC), to
      compare these results with manual scoring and routine histopathology, and to
      correlate them with the history of allergy or recurrence. METHODS: LSC was used
      for semi-automated analysis of single-cell preparations from representative
      ethmoidal polyps obtained during routine paranasal sinus surgery (n=41). This
      microscope-based instrument scans the cells after immobilization of cells on a
      glass slide and after triple staining of cytokeratin, eosinophilic granula, and
      DNA. The location of each cell is stored with the fluorescence data. Therefore,
      the morphology of every cell can be documented by re-staining with haemotoxylin
      and eosin and re-localization on the slide. Subsequently, slides were subjected
      to manual scoring. The remaining polyps were analysed by routine histopathology.
      RESULTS: Data from LSC and manual scoring showed good correlation (r=0.81,
      P<0.001), whereas there were discrepancies with histopathology. Eosinophilia
      scored by LSC and histopathology was neither correlated with the history of
      allergy nor with recurrence as determined by Fisher's exact test independent of
      the definition of eosinophilia (> or =2%, > or =3%, or > or =5% of all cells).
      CONCLUSION: Scoring eosinophilia by LSC in comparison with histopathology does
      not contribute to a more reliable basis for adjuvant medical therapy in nasal
      polyposis. Instead, functional parameters (cytokine production, apoptosis) may
      serve better.

PMID- 14720265
TI  - Provocation with adenosine 5'-monophosphate, but not methacholine, induces sputum
      eosinophilia.
AB  - INTRODUCTION: Bronchial hyper-responsiveness is usually measured with direct
      stimuli such as methacholine (MCh) or histamine. Adenosine 5'-monophosphate
      (AMP), which acts indirectly via the secondary release of mediators, is another
      stimulus to measure bronchial hyper-responsiveness. AIM: To investigate whether
      provocation with inhaled AMP itself initiates an inflammatory response resulting
      in an influx of eosinophils into the airway lumen. METHODS: We have included 21
      non-smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34
      years). Each subject performed three sputum inductions on different days, at
      least seven days apart: one without previous provocation, one hour after PC20
      methacholine, and one hour after PC20 AMP. RESULTS: After provocation with AMP,
      but not methacholine, the percentage of sputum eosinophils increased
      significantly (from 1.9+/-0.5% to 4.5+/-1% (P<0.01) and 1.9+/-0.5% (P=0.89)). No
      changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial
      epithelial cells were found. CONCLUSION: A provocation test with AMP leads to an
      increased percentage of sputum eosinophils. This observation cannot be explained
      by a non-specific response of the airways to a vigorous bronchoconstriction,
      since methacholine had no effect on inflammatory cells.

PMID- 14720266
TI  - Effect of a single dose of the selectin inhibitor TBC1269 on early and late
      asthmatic responses.
AB  - BACKGROUND: Selectins participate in the initial phase of leucocyte migration
      from circulation to inflamed tissues and may play a role in inflammatory cellular
      influx into airways in asthma. In the sheep asthma model, TBC1269, a pan-selectin
      antagonist, reduced late allergen response by 74%. OBJECTIVE: To determine
      whether a single dose of TBC1269 inhibits early (EAR) and late (LAR) asthmatic
      responses, and whether it inhibits sputum leucocyte influx after inhalation
      allergen challenge in atopic asthmatic subjects treated with bronchodilators
      only. METHODS: Twenty-one asthmatic subjects (mean+/-SD, age=32.5+/-6.7 years, 8
      males, FEV1 percent predicted=84+/-15%) with known late asthmatic response based
      on a screening inhalation allergen challenge were randomly assigned to receive
      intravenous treatment with either placebo (n=11) or TBC1269 (n=10, 30 mg/kg)
      infused over 15 min immediately prior to a second (post-treatment) allergen
      challenge at least 4 weeks after the screening challenge. After each challenge,
      EAR and LAR were monitored for 7 h. In addition, sputum was induced 1 day before
      and 1 day after each allergen challenge. RESULTS: TBC1269 did not attenuate the
      EAR compared with placebo (largest fall in FEV1 within 1 h of 34.1+/-13.9% vs.
      31.8+/-12.2% for TBC1269 and placebo groups respectively, P=0.61) or the LAR
      (largest fall in FEV1 between 3 and 7 h of 39.3+/-15.3% vs. 32.6+/-13.8%,
      P=0.24). TBC1269 had only minor effects on allergen-induced sputum eosinophilia.
      CONCLUSION: We conclude that TBC1269 administered before allergen challenge as a
      single intravenous dose does not attenuate early or late asthmatic responses to
      allergen in asthmatic subjects.

PMID- 14720267
TI  - Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal
      and dynamic measures of hypothalamic-pituitary-adrenal-axis activity in healthy
      volunteers.
AB  - BACKGROUND: Most published studies show that intranasal corticosteroids have no
      effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been
      isolated reports to the contrary, contradicting accumulated knowledge on
      pharmacokinetics. OBJECTIVE: To re-evaluate the effect of fluticasone propionate
      aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray
      on the HPA axis using an improved study design. METHODS: Twenty-three healthy
      volunteers were randomized in a double-blind, three-way crossover study. The
      study comprised a 4-day placebo run-in phase followed by three 4-day treatment
      periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220
      microg once daily)), separated by 7-14 days washout intervals. Before the first,
      and on the last day of each treatment period, 12-h overnight urine was collected
      to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h
      after the last administration of study medication, volunteers underwent
      stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol
      concentrations were measured before and 20 and 30 min after injection. Blood and
      urine samples were analysed for cortisol by liquid chromatography tandem mass
      spectrometry. RESULTS: Compared with placebo, EP or TAA had no significant effect
      on mean overnight (12 h) urinary cortisol excretion, and did not significantly
      suppress the overnight geometric mean urinary cortisol/creatinine excretion
      ratio. Values for serum cortisol before and after ACTH simulation showed no
      significant suppression, although there was a slight blunting of the HPA-axis
      response following TAA treatment. CONCLUSION: This study confirms that there are
      no detectable effects on the HPA axis following short-term intranasal FP or TAA
      at their recommended dosages.

PMID- 14720268
TI  - Early and late bronchoconstrictions, airway hyper-reactivity, leucocyte influx
      and lung histamine and nitric oxide after inhaled antigen: effects of
      dexamethasone and rolipram.
AB  - BACKGROUND: Guinea-pig models can provide the essential features of asthma,
      including early- (EAR) and late- (LAR) phase asthmatic responses, airway hyper
      reactivity (AHR) and inflammatory cell influx; however, these components are
      rarely demonstrated all in the same model. OBJECTIVES: The aim of this study was
      to establish a conscious guinea-pig model with these essential features of asthma
      and to correlate these with bronchoalveolar lavage fluid (BALF) histamine and
      nitric oxide (NO) levels. The model would be validated from the susceptibility of
      these parameters to standard anti-asthmatic agents, the steroid, dexamethasone,
      and a phosphodiesterase-4 (PDE4) inhibitor, rolipram. METHODS: Guinea-pigs were
      sensitized with ovalbumen (OA) (10 microg plus Al2(OH)3 100 mg, intraperitoneal
      (i.p.)) and 14 days later received inhaled OA (100 microg/mL) or vehicle for 1 h.
      Airway function was measured by whole-body plethysmography as specific airway
      conductance (sGaw). Reactivity to inhaled histamine (nose-only, 1 mm, 20 s) was
      recorded 24 h before and at 6, 12 or 24 h after OA challenge. BALF was obtained
      to determine the total and differential cell counts, NO and histamine. RESULTS:
      Guinea-pigs challenged with OA showed an EAR as a fall in (sGaw) (-54.9+/-10.8%),
      which resolved by 6 h and was followed by an LAR between 7 and 11 h (-30.2+/
      8.8%). No bronchoconstriction to inhaled histamine occurred before OA challenge
      but at 6, 12 or 24 h afterwards, sGaw fell significantly, indicating AHR. At 1 h
      after OA, macrophages, eosinophils and neutrophils significantly increased in
      BALF. Macrophages and eosinophils increased further up to 24 h (3- and 44-fold),
      but neutrophils declined to control levels. BALF histamine levels increased at
      0.25 h after OA challenge and peaked at 6 h. BALF NO levels initially fell (44%)
      1 h after OA exposure and then progressively rose above control levels.
      Dexamethasone (20 mg/kg, i.p.) and rolipram (1 mg/kg, i.p.) administered 24 and
      0.5 h before and 6 h after OA challenge inhibited leucocyte influx, AHR and the
      early deficiency and later excess of NO. Dexamethasone but not rolipram
      attenuated the LAR. CONCLUSIONS: This model displays many of the features of
      human asthma with predictable responses to dexamethasone and evidence of anti
      asthmatic activity by the PDE4 inhibitor, rolipram.

PMID- 14720269
TI  - Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage
      migration inhibitory factor: its potential anti-inflammatory action.
AB  - BACKGROUND: H1-receptor antagonists are often effective in the treatment of
      allergic disorders such as atopic dermatitis. Cetirizine, a putative H1-receptor
      antagonist, has recently been shown to have anti-inflammatory properties through
      the inhibition of leucocyte recruitment and activation, and by the reduction of
      ICAM-1 expression on keratinocytes. OBJECTIVE: To further elucidate the anti
      inflammatory properties of cetirizine, we first examined its effects on antigen
      induced eosinophilia and neutrophila in vivo. We then examined the anti
      inflammatory effects of cetirizine on a human keratinocyte A431cell line.
      METHODS: Mice were sensitized subcutaneously with ragweed pollen and were
      challenged intraperitoneally with the allergen. Cetirizine diluted in sterile
      water (0-20 mg/kg) or only sterile water was administered orally. Peritoneal
      cells were obtained at 8 and 24 h after challenge. The eosinophilia and
      neutrophilia induced by ragweed pollen extract were quantitated. Macrophage
      migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP-2) and
      eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The
      effects of cetirizine on MIF-induced IL-8 production in A431 cells were examined
      by ELISA. The effects of cetirizine on MIF expression and production in A431
      cells were examined by human MIF ELISA and Northern blot analysis. RESULTS:
      Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be
      significantly reduced in cetirizine-treated mice (20 mg/kg). MIF, a pleuripotent
      cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by
      cetirizine treatment. MIP-2 and eotaxin were also decreased 8 and 24 h,
      respectively, after challenge in the peritoneal fluid with cetirizine treatment.
      MIF stimulates IL-8 production in A431 cells. We found that MIF production in
      A431 cells was inhibited by 10 microm cetirizine. Consistent with this,
      cetirizine significantly inhibited MIF-induced IL-8 production. CONCLUSION: These
      results suggest that cetirizine exerts its anti-inflammatory effects by
      inhibiting MIF as well as IL-8 production, such as those involved in inflammatory
      allergic skin disease, suggesting a broad spectrum of action beyond its mere H1
      receptor-antagonistic function.

PMID- 14720270
TI  - Butterbur, a herbal remedy, confers complementary anti-inflammatory activity in
      asthmatic patients receiving inhaled corticosteroids.
AB  - BACKGROUND: The effects of butterbur (BB), a herbal remedy, as add-on therapy to
      inhaled corticosteroids in patients with atopic asthma is currently unknown.
      OBJECTIVE: We evaluated the effects of BB, given as add-on therapy to asthmatic
      patients maintained on inhaled corticosteroids, assessing adenosine monophosphate
      (AMP) bronchoprovocation (primary outcome variable) along with other surrogate
      inflammatory markers such as exhaled nitric oxide, serum eosinophil cationic
      protein and peripheral blood eosinophil count. METHODS: Sixteen atopic asthmatic
      patients with mean (standard error of mean) forced expiratory volume in 1 s
      (FEV1) of 78 (4)% predicted, maintained on their constant dose of inhaled
      corticosteroids throughout the study, received twice daily for 1 week either BB
      25 mg or placebo (PL), in a double-blind, cross-over fashion, with a 1-week
      washout period prior to each randomized treatment. Measurements were made at
      baselines prior to each randomized treatment and following the randomized
      treatment period. RESULTS: Baseline values for the primary and secondary outcomes
      were not significantly different prior to BB and PL. AMP provocative
      concentration causing a 20% reduction from baseline FEV1 (PC20) as doubling
      dilution change from baseline, significantly improved (P<0.05) with BB, 0.6
      (0.2), compared with PL, -0.1 (0.3); a 0.7 doubling dilution difference. Exhaled
      nitric oxide as change from baseline was significantly reduced (P<0.05) with BB, 
      1.2 (0.8) p.p.b., compared with PL, 0.5 (0.4) p.p.b. Both serum eosinophil
      cationic protein and peripheral blood eosinophil count as change from baseline
      were also significantly suppressed (P<0.05) with BB, -3.9 (3.3) microg/L, -31
      (28)x106/L compared with PL, 3.3 (2.5) microg/L, 38 (16)x106/L, respectively.
      CONCLUSION: Chronic dosing with BB conferred complementary anti-inflammatory
      activity in atopic asthmatic patients maintained on inhaled corticosteroids.
      Further studies are now required to assess the potential role for BB as either
      monotherapy in milder patients or add-on therapy in more severe asthmatics.

PMID- 14720271
TI  - Vaccines for birch pollen allergy based on genetically engineered hypoallergenic
      derivatives of the major birch pollen allergen, Bet v 1.
AB  - BACKGROUND: We have recently engineered recombinant derivatives of the major
      birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly
      reduced allergenic activity. OBJECTIVE: The aim of this study was the in vivo
      characterization of potential allergy vaccines based on Al(OH)3-adsorbed
      genetically modified rBet v 1 derivatives in mice. METHODS: BALB/c mice were
      immunized either with courses of nine injections of increasing doses of Al(OH)3
      adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone
      in weekly intervals or with three high-dose injections applied in intervals of 3
      weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant
      allergens were measured by ELISA and Western blotting, and the ability of mouse
      antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied
      by ELISA competition experiments. RESULTS: In both schemes, hypoallergenic rBet v
      1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type.
      The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross
      reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as
      hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic
      patients' IgE to Bet v 1 wild-type. CONCLUSION: Genetically modified
      hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their
      safety and efficacy for the treatment of birch pollen and associated plant
      allergies can now be evaluated in clinical immunotherapy studies.

PMID- 14720272
TI  - Cytokine production in peripheral blood cells during and outside the pollen
      season in birch-allergic patients and non-allergic controls.
AB  - BACKGROUND: The naturally occurring pollen season permits observation of the
      kinetic changes in the process of allergic inflammation. We examined cytokine
      production in peripheral blood (PB) T cells and monocytes obtained from birch
      allergic patients both during and outside the pollen season. METHODS: PB from 16
      patients and six healthy controls was obtained during the alder pollen season, at
      the beginning and the peak of the birch pollen season and outside the pollen
      season. Mononuclear cells (MNC) were stimulated with allergen and polyclonal
      activators. For flow cytometric analysis, MNC were stained with monoclonal
      antibodies (MoAbs) against the cell surface markers CD3, CD8, CD14 and the
      intracellular cytokines IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte macrophage
      colony stimulating factor (GM-CSF) and IFN-gamma. RESULTS: In allergic patients,
      significant increases in clinical symptoms, use of medication, eosinophil numbers
      and birch-specific IgE were found during the pollen season. In vitro allergen
      stimulation increased the number of GM-CSF+ monocytes (P<0.01) and this increase
      was dependent on allergen exposure. The IL-4/IFN-gamma ratio rose (P<0.001) at
      the peak of birch pollen season and the ratio correlated with symptom scores
      during the birch season. In the CD4+ cell population, the numbers of GM-CSF+
      cells were higher throughout the alder and birch seasons compared with outside
      the pollen season (P<0.05). No such changes were seen in the healthy controls.
      CONCLUSIONS: The main finding of our study was the increased percentage of GM
      CSF+ monocytes in atopic subjects compared with healthy controls. In allergic
      patients, natural seasonal pollen exposure resulted in increased numbers of GM
      CSF+ cells among both monocytes and CD4+ T cells. We have also shown that a
      seasonal change in Th2/Th1 cytokine ratio requires an adequate and prolonged
      allergen stimulation that is seen late in the pollen season.

PMID- 14720273
TI  - Diversity of asparagus allergy: clinical and immunological features.
AB  - BACKGROUND: Asparagus (Asparagus officinalis) is an extensively grown and
      consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic
      contact dermatitis (ACD) due to asparagus has been reported. However, only a few
      case reports of asparagus IgE-mediated allergy have been published. In a previous
      study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and
      Aspa o 1.02) were relevant allergens of asparagus. OBJECTIVE: We retrospectively
      analysed the 27 patients diagnosed with asparagus allergy during the last 5
      years. All of them reported adverse symptoms after either asparagus ingestion or
      handling. We describe their clinical features and evaluate whether they were
      associated to immunological findings (immunoblot pattern and skin reactivity to
      LTPs). METHODS: Patients underwent skin prick and patch tests with standard
      panels of vegetables and aeroallergens. Besides crude asparagus extract, two
      purified LTPs were prick and patch tested. Total and specific IgE measurements
      and asparagus extract IgE immunoblotting were performed. Patients reporting
      asthma symptoms underwent specific inhalation challenge to asparagus. RESULTS: Of
      the 27 subjects, eight had ACD, 17 had IgE-mediated allergy and two had both ACD-
      and IgE-mediated allergy. Positive patch tests with the crude asparagus extract
      but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with
      IgE-mediated disease, 10 had contact urticaria after asparagus handling. Of them,
      five subjects and five others without skin allergy showed respiratory symptoms;
      of them, eight were diagnosed with occupational asthma confirmed by positive
      asparagus inhalation challenge, whereas the remaining two had isolated rhinitis.
      Four patients suffered from immediate allergic reactions related to asparagus
      ingestion (food allergy); three of them reported anaphylaxis whereas the other
      had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45-70
      kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to
      LTPs, six showed bands at 15 kDa. Either IgE-binding bands or positive prick
      tests to LTPs were observed in asthma (62%) and anaphylaxis (67%). CONCLUSION:
      Asparagus is a relevant source of occupational allergy inducing ACD and also IgE
      mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs
      seem to play a major role. The clinical relevance of LTP sensitization among
      patients with mild disease or symptom-free subjects should be addressed in
      prospective studies.

PMID- 14720274
TI  - Sensitization to cross-reactive carbohydrate determinants and the ubiquitous
      protein profilin: mimickers of allergy.
AB  - BACKGROUND: During the last decade, evidence has been provided for profilins and
      cross-reactive carbohydrate determinants (CCDs) to be capable of inducing cross
      reactive IgE antibodies with little clinical relevance. OBJECTIVE: To investigate
      the prevalence of sensitization to CCD and profilin in isolated allergies (birch,
      timothy grass, house dust mite, pets (cat and/or dog), natural rubber latex (NRL)
      and hymenoptera venom). To study the contribution of anti-CCD and anti-profilin
      IgE antibodies as a cause of clinically irrelevant IgE for NRL and apple.
      METHODS: For the first part of the study, 100 patients with inhalant allergy, 17
      patients with NRL allergy and 40 patients with venom anaphylaxis were enrolled.
      Diagnosis was based on a questionnaire and a positive IgE determination and skin
      test for relevant allergen. Patients were identified as sensitized to CCD if they
      had a negative prick test and positive IgE for the glycoprotein bromelain.
      Sensitization to profilin was assessed by IgE for rBet v 2 (recombinant birch
      profilin). For the second part of the study, sera containing IgE against apple
      (n=82) or NRL (n=38) were classified as true-negative or false-positive according
      to the presence or absence of an oral allergy syndrome (OAS) or NRL-induced
      anaphylaxis. In these patients, sensitization to CCD and profilin was evaluated
      as described above. RESULTS: No sensitization to bromelain-type CCD and profilin
      was found in isolated birch pollen or NRL allergy. In contrast, sensitization to
      bromelain-type CCD was found in 4/17 patients with isolated grass pollinosis,
      5/24 patients with combined pollinosis (birch, timothy, mugwort) and 7/33
      patients with venom anaphylaxis. Sensitization to profilin was almost restricted
      to patients with combined pollen allergy (5/24). In pollen-allergic individuals
      with a false-positive IgE against NRL the prevalence of sensitization to
      bromelain-type CCD and profilin IgE was higher than in NRL-allergic patients
      (P<0.00001 and P=0.0006, respectively). In pollen-allergic individuals with a
      false-positive IgE to apple, the frequency of sensitization to bromelain-type CCD
      was higher than in OAS patients (P=0.004). Clinically irrelevant NRL and apple
      were also found in four and five out of the seven patients sensitized to venom
      CCD, respectively. In pollinosis, clinically irrelevant NRL and apple IgE
      antibodies were inhibited by bromelain and recombinant birch profilin, whereas in
      isolated venom anaphylaxis these antibodies were inhibited by bromelain.
      CONCLUSIONS: Patients monoallergic to NRL or birch pollen showed no sensitization
      to bromelain-type CCD or profilin. Sensitization to profilin and/or bromelain
      type CCD, caused by pollen (timothy grass, mugwort) or hymenoptera venom
      allergens, can elicit false-positive IgE antibodies against NRL and apple.

PMID- 14720275
TI  - Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist
      treatments in an experimental model of chronic airway inflammation in guinea
      pigs.
AB  - BACKGROUND: Leukotriene receptor antagonists have been demonstrated in several
      studies to possess bronchodilating and anti-inflammatory properties in asthma.
      However, there are few experimental studies performed to compare the effects of
      anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in
      asthma. In the present study, we evaluated the effects of treatment with
      dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an
      experimental model of allergen-induced chronic airway inflammation in guinea-pigs
      (GP). METHODS: GP were submitted to increasing concentrations of aerosols of
      ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated
      daily with dexamethasone, montelukast or saline solution. After this period, GP
      were anaesthetized, tracheostomized, mechanically ventilated and challenged with
      OVA aerosol. RESULTS: Maximal changes of respiratory system resistance and
      elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001),
      but not by montelukast treatment. Neither dexamethasone nor montelukast
      significantly influenced bronchial oedema formation. Dexamethasone but not
      montelukast induced a decrease in mononuclear cells in airways (P<0.001).
      Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone
      and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of
      exhaled nitric oxide (P<0.025). CONCLUSION: Although leukotriene receptor
      antagonist treatment reduces eosinophil accumulation induced by multiple antigen
      challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear
      cell infiltration.

PMID- 14720280
TI  - Artificial organs: a perspective on the field.

PMID- 14720279
TI  - The need for international communications in artificial organs research and
      development and clinical practice.

PMID- 14720281
TI  - Ethical and design issues in heart replacement in Asia.

PMID- 14720282
TI  - Studies on regenerative medicine in Japan.

PMID- 14720283
TI  - Establishment of banking system for allogeneic cultured dermal substitute.
AB  - Allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts
      on a two-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col).
      Allogeneic CDS can be cryopreserved and transported to other hospitals in a
      frozen state. Vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), hepatocyte growth factor (HGF), platelet derived growth factor
      (PDGF)-AA, transforming growth factor (TGF)-beta1, keratinocytes growth factor
      (KGF), interleukin (IL)-6 and IL-8 were contained in the culture medium which was
      used in preparing CDS over a cultivation period of one week (fresh CDS culture
      medium sample). After thawing a cryopreserved CDS, the CDS was recultured in a
      culture medium for one week. VEGF, bFGF, HGF, TGF-beta1 and IL-8 were contained
      in the culture medium which was used in reculturing CDS for one week
      (cryopreserved CDS culture medium sample), although some cytokines were detected
      at a lower level than those before freezing. This finding suggests that the
      cryopreserved CDS retains its ability to release these cytokines. Clinical
      research on allogeneic CDS, which was newly developed at the R & D Center for
      Artificial Skin of Kitasato University, has been carried out in medical centers
      across Japan with the support of the Millennium Project of the Ministry of
      Health, Labor and Welfare. It was demonstrated that the allogeneic CDS functions
      as an excellent cell therapy for intractable skin ulcers as well as burn
      injuries. The spongy matrix itself, as well as the cytokines released from the
      allogeneic CDS, seemed to be beneficial for the treatment of intractable skin
      defect.

PMID- 14720284
TI  - Development of cultivated mucosal epithelial sheet transplantation for ocular
      surface reconstruction.
AB  - Regenerative medicine via tissue engineering is a newly developed medical field
      based on the use of somatic stem cells to generate biological substitutes and
      improve tissue functions. The achievement of these objectives depends on two
      important factors: stem cells, which are high in proliferability and
      differentiability, and the substrates that support them. In order to reconstruct
      the ocular surface in patients with severe ocular surface diseases, we decided to
      investigate the feasibility of human amniotic membrane as an epithelial carrier,
      and found that denuded amniotic membrane was the most appropriate substrate for
      this purpose. To develop the surgical treatment using denuded amniotic membrane
      as a carrier, we established the tissue engineering system for making
      transplantable epithelial sheets of either corneal or oral mucosal epithelial
      cells for ocular surface reconstruction.

PMID- 14720285
TI  - Articular cartilage repair using tissue engineering technique--novel approach
      with minimally invasive procedure.
AB  - Articular cartilage has very limited potential to spontaneously heal, because it
      lacks vessels and is isolated from systemic regulation. Although there have been
      many attempts to treat articular cartilage defects, such as drilling,
      microfracture techniques, soft tissue grafts or osteochondral grafts, no
      treatment has managed to repair the defects with long-lasting hyaline cartilage.
      Recently, a regenerative medicine using a tissue engineering technique for
      cartilage repair has been given much attention in the orthopedic field. In 1994,
      Brittberg et al. introduced a new cell technology in which chondrocytes expanded
      in monolayer culture were transplanted into the cartilage defect of the knee. As
      a second generation of chondrocyte transplantation, since 1996 we have been
      performing transplantation of tissue-engineered cartilage made ex vivo for the
      treatment of osteochondral defects of the joints. This signifies a concept shift
      from cell transplantation to tissue transplantation made ex vivo using tissue
      engineering techniques. We have reported good clinical results with this surgical
      treatment. However, extensive basic research is vital to achieve better clinical
      results with this tissue engineering technique. This article describes our recent
      research using a minimally invasive tissue engineering technique to promote
      cartilage regeneration.

PMID- 14720286
TI  - Cultured autologous human cells for hard tissue regeneration: preparation and
      characterization of mesenchymal stem cells from bone marrow.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells and can be induced in vitro
      and in vivo to differentiate not only into the variety of mesodermal cells, but
      into either ectodermal or endodermal cells. This capability indicates the
      usefulness of MSCs for tissue engineering. Cell surface antigen analyses using
      various types of CD antibodies demonstrated that adherent fibroblastic cells
      derived from fresh human bone marrow are mesenchymal types and the cells showed
      extensive capability for proliferation and/or differentiation. We labeled the
      adherent cultured marrow cells as MSCs and, significantly, found the MSCs could
      even proliferate from aged marrow cells. After about sixteen days of culturing,
      we were able to harvest 100 million MSCs from only 3 ml of fresh human marrow.
      Moreover, the MSCs could be cryopreserved at -80 degrees C without noticeable
      loss of viability and capability of osteoblastic differentiation. These results
      indicate that MSCs hold promise for utilization in hard tissue regeneration.

PMID- 14720287
TI  - Cell-based therapy to regenerate myocardium: from bench to bedside.
AB  - The field of cell-based therapy to regenerate myocardium has been expanding
      rapidly, with significant advances being made in both the laboratory and the
      clinical area. In this article we review this field, including our experiences
      and discuss remaining issues and possibilities for future clinical applications.

PMID- 14720288
TI  - Bioartificial pancreas research in Japan.
AB  - The bioartificial pancreas (BAP), a medical device enclosing insulin-secreting
      cells in a semipermeable membrane, is expected to physiologically control glucose
      levels, and thus to be able to inhibit development of serious chronic
      complications in diabetic patients. In this brief review, we introduce research
      activities on the development of the BAP in Japan, including membrane preparation
      for the BAP, evaluation of in vitro and in vivo BAP functions, and challenges for
      production of insulin-secreting cells from stem cells.

PMID- 14720289
TI  - Liver regeneration using a hybrid artificial liver support system.
AB  - We have developed two types of hybrid artificial liver support system (HALSS)
      that use hepatocyte organoid culture: (1) a PUF-HALSS comprising an artificial
      liver module using polyurethane foam (PUF), in which hepatocytes form spheroids
      in its pores, and maintained liver-specific functions for at least ten days in
      vitro; (2) an LLS-HALSS that uses a liver lobule-like structure (LLS) module
      containing hollow fibers with a microregular arrangement in which hepatocytes in
      the extra-fiber space of the module form the organoids by centrifugation that
      maintain liver-specific functions for at least two months in vitro. In
      preclinical experiments, a PUF-HALSS was applied to a pig having liver failure.
      To evaluate the effect of liver regeneration, a PUF- and an LLS-HALSS were
      applied to a rat having reversible hepatic failure. Each HALSS was effective in
      supporting liver function, stabilization of general conditions and recovery from
      liver failure state. These results indicate that these HALSS may be useful to
      treat liver failure patients until liver transplantation or until regeneration of
      the native liver.

PMID- 14720290
TI  - Research into the development of a wearable bioartificial kidney with a
      continuous hemofilter and a bioartificial tubule device using tubular epithelial
      cells.
AB  - Current hemodialysis treatment is insufficient because of intermittent treatment
      and loss of tubular function. In order to overcome the loss of tubular function,
      a bioartificial kidney has been developed consisting of continuous hemofiltration
      (CHF) with 10 L/day of filtrate and a bioartificial tubule device using proximal
      tubular epithelial cells and hollow fiber membranes. Ten L/day of CHF enabled
      plasma levels of urea, creatinine, uric acid and, beta2-microglobulin in eight
      renal failure patients to be maintained at remarkably low levels. The concept was
      tested with 6 L (4 mL/min) of 10 L/day (7 mL/min) filtrate regenerated by a
      bioartificial tubule device and 4 L/day (3 mL/min) replaced by food and drinks.
      Lewis lung cancer-porcine kidney 1 (LLC-PK1) cells with a cell density of 107
      cells/mL were seeded inside polysulfone hollow fiber modules four times at 1 h
      intervals while rotating the module 90 degrees each time, and were cultured for
      48 h to form confluent monolayers. The leak rates of urea and creatinine across
      LLC-PK1 cell-attached polysulfone membrane modules (membrane areas: 56 cm2 and
      4000 cm2) were investigated. Via conversion from 56 m2 to 1 m2 hollow fiber
      modules with LLC-PK1 cells for 24 h, the transport rates of H2O, glucose and Na+
      were, respectively, 40, 65 and 35% of the target transported amounts from 6 L/day
      of filtrate. The rates are expected to approach 100% when 4-5 g/dL of albumin is
      added to the basal portion of the medium since the results were obtained without
      the addition of albumin for colloidal osmotic pressure.

PMID- 14720291
TI  - Recent progress of vascular graft engineering in Japan.
AB  - The development of a small-diameter vascular graft has long been awaited. This
      review covers research activities, achievements and progress on vascular
      engineering in Japan, which was conducted over the last decade. The article
      includes recently developed experimental scaffolds, biologically active
      artificial extracellular matrices (ECMs) or non-fouling synthetic coatings, cell
      sourcing including the autologous vascular cell type, endothelial progenitor
      cells and genetically-engineered, temporary endothelial-like cells. The
      discussions were presented from biomechanical, biomaterial, cellular and tissue
      aspects. Once the mechano-biological and biologically active extracellular
      milieus are established in a designed vascular graft, the functional, structural
      and mechanical tissue morphogenesis and adaptation of implanted vascular grafts
      may proceed with implantation duration, and the spatio-temporal tissue
      modulations at cytokine, cellular, ECM levels under physiological stress proceed
      to regenerate vascular tissue architecture. The ultimate solution to a small
      diameter vascular graft should be realized by optimal combinations of these
      factors.

PMID- 14720292
TI  - Osteogenic differentiation of human bone marrow-derived mesenchymal cells
      cultured on alumina ceramics.
AB  - Alumina ceramics have excellent mechanical and biocompatible properties, but are
      bioinert and hence have no bone-bonding properties. We took a tissue-engineering
      approach in an attempt to modify the ceramic surface and so provide an
      osteogenic/osteoconductive milieu. We obtained human bone marrow mesenchymal
      cells from four donors and then cultured the cells for two weeks on alumina
      ceramic in the presence of beta-glycerophosphate, ascorbic acid and
      dexamethasone. The cells showed extensive alkaline phosphatase staining and
      mineralization, as evidenced by Alizarin Red S staining and calcein uptake.
      Biochemical analyses revealed high levels of alkaline phosphatase activity,
      osteocalcin expression and calcium content. This data indicates the appearance of
      active osteoblasts that are concomitant with bone matrix formation, i.e., in
      vitro cultured bone. The cultured bone/alumina composites should prevent the
      aseptic loosening of all-alumina ceramic joints or the detachment of implanted
      alumina ceramics, and thus could have clinical significance in orthopedic
      reconstructive surgery.

PMID- 14720293
TI  - Oxygen consumption in a hollow fiber bioartificial liver--revisited.
AB  - Oxygen consumption dynamics in a hollow fiber, hepatocyte-loaded bioartificial
      liver are investigated both theoretically and experimentally. The theoretical
      model is based upon the Krogh cylinder, which approximates the bioreactor as a
      collection of cylindrical elements comprised of an inner fiber lumen for media
      perfusion, the fiber wall through which oxygen can diffuse, and an annular region
      of hepatocytes surrounding the fiber. The primary non-dimensional parameters that
      describe the system are: (i) the Peclet number, Pe, which is the ratio of
      convective oxygen transport through the lumen to diffusive oxygen transport to
      the fiber walls; (ii) the hepatocyte saturation parameter, theta, which is the
      ratio of the inlet oxygen partial pressure to the Michaelis-Menten half-rate
      oxygen partial pressure; (iii) the Thiele modulus, phi2, which is the ratio of
      oxygen consumption rate to oxygen diffusion rate in the hepatocyte annulus; (iv)
      the hepatocyte permeability ratio, beta31, which is the ratio of oxygen
      permeability in the hepatocyte cell mass to oxygen permeability in the perfusing
      lumen medium; and (v) the hepatocyte annular thickness, rho3, which is the ratio
      of the exterior hepatocyte annular radius to the fiber lumen radius. Only Pe and
      theta are easily manipulated operating variables. phi2, beta31, and rho3 are
      engineering design parameters that are set when a bioreactor is fabricated. The
      model results are expressed as the effective hepatocyte utilization ratio,
      Vratio, which is the ratio of the observed oxygen consumption rate to the
      intrinsic hepatocyte oxygen consumption rate. Large regions of Vratio > 0.9,
      which is deemed an acceptable effective hepatocyte utilization are found for
      parameter values consistent with standard hollow fiber cartridges used in
      bioartificial liver fabrication. The extent of the Vratio > 0.9 region increases
      to a plateau with increasing Pe, increases with increasing theta, decreases with
      increasing phi2, increases with increasing beta31, and decreases with increasing
      rho3. The theoretical results indicate that Vratio > 0.9 is found whenever the
      experimentally observed fractional oxygen consumption from the perfusing medium,
      is less than 0.25. Combination of the theoretical and experimental results
      indicate that intrinsic, per cell oxygen consumption in the hollow fiber system
      may decrease as hepatocyte cell density increases and that this decrease may be
      due to lower intrinsic oxygen requirements in denser suspensions and not due to
      diffusion limitations in oxygen transport in the hollow fiber system as might be
      expected from two-dimensional, monolayer culture oxygen consumption measurements.

PMID- 14720294
TI  - Long-term transcutaneous neuromuscular electrical stimulation in patients with
      bipolar sensing implantable cardioverter defibrillators: a pilot safety study.
AB  - Neuromuscular electrical stimulation (NMES) is an option for increasing thigh
      muscle strength and endurance capacity in patients with chronic heart failure.
      Electromagnetic interference (EMI) by the signals with sensing of implantable
      cardioverter defibrillators (ICDs) is possible. The aim of the present pilot
      safety study was to test the safety of a long-term NMES in patients with ICDs.
      Six patients with subpectoral ICDs were subjected to long-term NMES of thigh
      muscles. Four inpatients received NMES to increase muscle strength, and two
      outpatients performed NMES as a home treatment to increase endurance capacity.
      During long-term NMES, all patients together received 14 139 799 biphasic
      electrical pulses and 412 425 on-phases without adverse events. ICD function
      after the stimulation period revealed no abnormalities in any patient. These
      results indicate that long-term NMES of thigh muscles seems to be safe in
      patients with ICDs, providing that an individual risk is excluded before.

PMID- 14720295
TI  - Initial experience with a new right ventricular support device for beating heart
      surgery.
AB  - OBJECTIVE: Device supported beating heart surgery has been advocated to extend
      patient selection criteria for off-pump surgery. This article reports the initial
      experimental and clinical results with a novel paracardial right ventricular
      support device. METHODS: Preclinical experiments were performed in two pigs. Ten
      elective patients with triple vessel disease were subjected to beating heart
      coronary artery bypass grafting surgery during right ventricular support by the
      paracardial device. Measurements included intraoperative hemodynamics during
      cardiac tilting, perioperative left ventricular ejection fraction (LVEF),
      hemolysis parameters, mortality and major morbidity events. RESULTS: A mean of
      3.2 +/- 0.2 distal anastomoses per patient were performed. Mean arterial pressure
      and central venous oxygen saturation remained stable during cardiac tilting.
      Perioperative LVEF did not vary significantly. Sixty-day mortality and
      postoperative infarction rate were 0%. Functional Canadian Cardiovascular Society
      class at 6 days after surgery was 1.2 +/- 0.1 vs. 3.3 +/- 0.2 pre-operatively.
      CONCLUSION: In this initial clinical experience, application of the novel
      paracardial right ventricular support device proved to be safe and efficient.

PMID- 14720296
TI  - Open-loop analysis of transfer characteristics from blood pressure to heart rate
      using an effectively total artificial heart.
AB  - It is desirable for the dynamic behavior of the drive rate of the artificial
      heart to be as similar as possible to that of the recipient's heart rate (HR)
      before implantation. This requires a model which can simulate the behavior of HR
      on the basis of only the information measured with the limited number of
      approvable implanted sensors. This article provides a linear time series model
      for explaining the behavior of HR only with aortic pressure and right atrial
      pressure. This could be obtained from open-loop analysis using a total artificial
      heart, which was introduced for measuring HR in vivo and for eliminating its
      effect on blood pressure. The model was identified in a goat equipped with a
      special biventricular assist device called the effectively total artificial heart
      (ETAH). The ETAH was introduced to make an open loop and awake situation in the
      animal with almost intact autonomic nerves, which could enhance the accuracy and
      reliability of the identification of the model. The adequacy of the proposed
      model was ascertained in several data sets measured in two goats, which were
      different from the data set used for identification. Most of the mean estimation
      errors were less than 3 beats/min and auto-correlation analysis showed approvable
      statistical appropriateness. However, it was clarified through comparison with
      the 1/R control method that the proposed model has a few problems still to be
      solved before its future implementation as an automatic controller of the TAH.

PMID- 14720297
TI  - The action of low-intensity pulsed ultrasound in bones of osteopenic rats.
AB  - In this study, the action of low-intensity pulsed ultrasound for 20 min/day,
      during twenty days, was analyzed in an attempt to revert bone loss in the
      proximal femur of osteopenic rats. Although the quantitative results of bone
      mineral content (BMC) demonstrated no significant difference among the groups (P
      > 0.05), the histologic investigations have shown the occurrence of recent bone
      formation not observed in the nontreated group. Moreover, the treated femur
      presented less microarchitectural deterioration than the nontreated group. These
      results suggest that the low-intensity ultrasound can interfere in a positive way
      on osteoporosis.

PMID- 14720298
TI  - International Center for Medical Technologies acknowledges Artificial Organ
      Pioneers at the ASAIO-ISAO Joint Congress in 2003.
AB  - The International Center for Medical Technologies (ICMT), a museum for artificial
      organs in Houston, Texas, officially opened in November 2002, as previously
      published in Artificial Organs 2003;27(9):821-32. The museum expanded its
      original activities to formulate the International Academy for Artificial Organ
      Pioneers (Academy) and the International Faculty for Health and Medical
      Technologies (Faculty). At the joint American Society for Artificial Internal
      Organs (ASAIO) and International Society for Artificial Organs (ISAO) Congress in
      Washington, DC on June 18, 2003, Yukihiko Nose introduced the ICMT and its
      formulation. The activities and future perspectives were presented by the ICMT
      Museum Director, Steven Phillips; the Academy Dean, Lowell Harmison; and the
      Faculty Dean, Michael E. DeBakey.

PMID- 14720299
TI  - Use of viral promoters in mammalian cell-based bioassays: How reliable?
AB  - Cell-based bioassays have been suggested for screening of hormones and drug
      bioactivities. They are a plausible alternative to animal based methods. The
      technique used is called receptor/reporter system. Receptor/reporter system was
      initially developed as a research technique to understand gene function. Often
      reporter constructs containing viral promoters were used because they could be
      expressed with very 'high' magnitude in a variety of cell types in the
      laboratory. On the other hand mammalian genes are expressed in a cell/tissue
      specific manner, which makes them (i.e. cells/tissues) specialized for specific
      function in vivo. Therefore, if the receptor/reporter system is to be used as a
      cell-based screen for testing of hormones and drugs for human therapy then the
      choice of cell line as well as the promoter in the reporter module is of prime
      importance so as to get a realistic measure of the bioactivities of 'test'
      compounds. We evaluated two conventionally used viral promoters and a natural
      mammalian promoter, regulated by steroid hormone progesterone, in a cell-based
      receptor/reporter system. The promoters were spliced into vectors expressing
      enzyme CAT (chloramphenicol acetyl transferase), which served as a reporter of
      their magnitudes and consistencies in controlling gene expressions. They were
      introduced into breast cell lines T47D and MCF-7, which served as a cell-based
      source of progesterone receptors. The yardstick of their reliability was highest
      magnitude as well as consistency in CAT expression on induction by sequential
      doses of progesterone. All the promoters responded to induction by progesterone
      doses ranging from 10-12 to 10-6 molar by expressing CAT enzyme, albeit with
      varying magnitudes and consistencies. The natural mammalian promoter showed the
      most coherence in magnitude as well as dose dependent expression profile in both
      the cell lines. Our study casts doubts on use of viral promoters in a cell-based
      bioassay for measuring bioactivities of drugs and hormones for human therapy and
      suggests caution regardingtranslation in toto, of a research technique as a cell
      based bioassay for drug screening.

PMID- 14720300
TI  - Health-related quality of life among older adults with arthritis.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is a key outcome in arthritis,
      but few population-based studies have examined the relationship of specific
      arthritic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA)
      with HRQOL. METHODS: Older adults in Pennsylvania completed a mail version of the
      Centers for Disease Control and Prevention (CDC) HRQOL modules. Medicare data
      were used to identify subjects with OA, RA, and no arthritis diagnosis. We
      compared HRQOL responses among these groups, and we also examined relationships
      of demographic characteristics to HRQOL among subjects with arthritis. RESULTS:
      In analyses controlling for demographic characteristics and comorbidity, subjects
      with OA and RA had poorer scores than those without arthritis on all HRQOL items,
      including general health, physical health, mental health, activity limitation,
      pain, sleep, and feeling healthy and full of energy. HRQOL scores were also lower
      for those with RA compared to OA. Among individuals with arthritis, all subject
      characteristics (including age, race, sex, nursing home residence, marital
      status, income, and comorbid illnesses) were significantly related to at least
      one HRQOL item. Older age, nursing home residence, and greater comorbidity were
      the most consistently associated with poorer HRQOL. CONCLUSIONS: Results of this
      study show that both OA and RA have a significant impact on multiple dimensions
      of HRQOL among older adults. Results also suggest the CDC HRQOL items are
      suitable for use among older adults and in mail surveys. Due to the rising number
      of older adults in many countries, the public health burden of arthritis is
      expected to increase dramatically. Efforts are needed to enhance access to
      medical care and disseminate self-management interventions for arthritis.

PMID- 14720301
TI  - Dendritic cells: In the forefront of immunopathogenesis and vaccine development -
      A review.
AB  - Dendritic cellls (DCs) comprise an essential component of the immune system.
      These cells, as antigen presenting cells (APCs) to naive T cells, are crucial in
      the initiation of antigen specific immune responses. In the past years, several
      DC subsets have been identified in different organs which exert different effects
      in order to elicit adaptive immune responses. Thus, identification of such DC
      subsets has led to a better understanding of their distribution and function in
      the body. In this review, several key properties of the immunobiology,
      immunopathogenesis and vaccine strategies using DCs will be discussed.

PMID- 14720302
TI  - A comparison of Power Doppler with conventional sonographic imaging for the
      evaluation of renal artery stenosis.
AB  - BACKGROUND: Power Doppler (PD) has improved diagnostic capabilities of vascular
      sonography, mainly because it is independent from the angle of insonation. We
      evaluated this technique in a prospective comparison with conventional imaging,
      consisting in Duplex and Color Doppler, for the evaluation of Renal Artery (RA)
      stenosis. METHODS: Sensitivity, specificity and predictive values of PD and
      conventional imaging were assessed in a blinded fashion on eighteen patients, 9
      with angiographic evidence of unilateral RA stenosis (hypertensive patients) and
      9 with angiographically normal arteries (control group). PD images were
      interpreted with an angiography-like criteria. RESULTS: In the control group both
      techniques allowed correct visualization of 16 out of the 18 normal arteries (93%
      specificity). Only in five hypertensive patients RA stenosis was correctly
      identified with conventional technique (56% sensitivity and 86% negative
      predictive value); PD was successful in all hypertensive patients (100%
      sensitivity and negative predictive value), since the operators could obtain in
      each case of RA stenosis a sharp color signal of the whole vessel with a clear
      "minus" at the point of narrowing of the lumen. All results were statistically
      significant (p < 0.01). CONCLUSIONS: This study demonstrates that PD is superior
      to conventional imaging, in terms of sensitivity and specificity, for the
      diagnosis of RA stenosis, because it allows a clear visualization of the whole
      stenotic vascular lumen. Especially if it is used in concert with the other
      sonographic techniques, PD can enable a more accurate imaging of renovascular
      disease with results that seem comparable to selective angiography.

PMID- 14720303
TI  - Imaging genome abnormalities in cancer research.
AB  - Increasing attention is focusing on chromosomal and genome structure in cancer
      research due to the fact that genomic instability plays a principal role in
      cancer initiation, progression and response to chemotherapeutic agents. The
      integrity of the genome (including structural, behavioral and functional aspects)
      of normal and cancer cells can be monitored with direct visualization by using a
      variety of cutting edge molecular cytogenetic technologies that are now available
      in the field of cancer research. Examples are presented in this review by
      grouping these methodologies into four categories visualizing different yet
      closely related major levels of genome structures. An integrated discussion is
      also presented on several ongoing projects involving the illustration of mitotic
      and meiotic chromatin loops; the identification of defective mitotic figures
      (DMF), a new type of chromosomal aberration capable of monitoring condensation
      defects in cancer; the establishment of a method that uses Non-Clonal Chromosomal
      Aberrations (NCCAs) as an index to monitor genomic instability; and the
      characterization of apoptosis related chromosomal fragmentations caused by drug
      treatments.

PMID- 14720304
TI  - Stampidine prevents mortality in an experimental mouse model of viral hemorrhagic
      fever caused by lassa virus.
AB  - BACKGROUND: The potential use of microorganisms as agents of biological warfare
      (BW) is a growing concern. Lassa virus, a member of the Arenavirus class of
      Hemorrhagic fever (HF) viruses has emerged as a worldwide concern among public
      health officials. The purpose of the present study was to further elucidate the
      antiviral activity spectrum of stampidine, a novel nucleoside analog with potent
      anti-viral activity against the immunodeficiency viruses HIV-1, HIV-2, and FIV,
      by examining its effects on survival of mice challenged with Lassa virus.
      METHODS: We examined the therapeutic effect of Stampidine in CBA mice inoculated
      with intracerebral injections of the Josiah strain of Lassa virus. Mice were
      treated either with vehicle or nontoxic doses of stampidine administered
      intraperitoneally 24 hours prior to, 1 hour prior to, and 24 hours, 48 hours, 72
      hours, and 96 hours after virus inoculation. RESULTS: The probability of survival
      following the Lassa challenge was significantly improved for stampidine treated
      mice (Kaplan Meier, Chi-squared = 11.7, df = 2, Log-Rank p-value = 0.003).
      CONCLUSION: Therefore, stampidine shows clinical potential as a new agent for
      treatment of viral hemorrhagic fevers caused by Lassa virus.

PMID- 14720306
TI  - Sucrose density gradient centrifugation and cross-flow filtration methods for the
      production of arbovirus antigens inactivated by binary ethylenimine.
AB  - BACKGROUND: Sucrose density gradient centrifugation and cross-flow filtration
      methods have been developed and standardised for the safe and reproducible
      production of inactivated arbovirus antigens which are appropriate for use in
      diagnostic serological applications. METHODS: To optimise the maximum titre of
      growth during the propagation of arboviruses, the multiplicity of infection and
      choice of cell line were investigated using stocks of Ross River virus and Barmah
      Forest virus grown in both mosquito and mammalian cell lines. To standardise and
      improve the efficacy of the inactivation of arboviral suspensions, stocks of Ross
      River virus, Barmah Forest virus, Japanese encephalitis virus, Murray Valley
      encephalitis virus and Alfuy virus were chemically inactivated using binary
      ethylenimine at a final concentration of 3 mM. Aliquots were then taken at hourly
      intervals and crude inactivation rates were determined for each virus using a
      plaque assay. To ensure complete inactivation, the same aliquots were each
      passaged 3 times in Aedes albopictus C6/36 cells and the presence of viral growth
      was detected using an immunofluorescent assay. For larger quantities of viral
      suspensions, centrifugation on an isopycnic sucrose density gradient or cross
      flow filtration was used to produce concentrated, pure antigens or partially
      concentrated, semi-purified antigens respectively. RESULTS: The results of the
      propagation experiments suggested that the maximum viral titres obtained for both
      Ross River virus and Barmah Forest virus were affected by the incubation period
      and choice of cell line, rather than the use of different multiplicity of
      infection values. Results of the binary ethylenimine inactivation trial suggested
      that standardised periods of 5 or 8 hours would be suitable to ensure effective
      and complete inactivation for a number of different arboviral antigens.
      CONCLUSION: Two methods used to prepare inactivated arbovirus antigens have been
      standardised to minimise production failure and expenditure and to provide
      reagents that conform to the highest quality and safety requirements of a
      diagnostic serology laboratory. The antigens are suitable for use in either
      enzyme linked immunosorbent assays or haemagglutination inhibition assays and the
      optimised protocols can be directly applied to produce antigens from new or
      emerging arboviral pathogens.

PMID- 14720305
TI  - TGF-beta1 induction of the adenine nucleotide translocator 1 in astrocytes occurs
      through Smads and Sp1 transcription factors.
AB  - BACKGROUND: The adenine nucleotide translocator 1 (Ant1) is an inner
      mitochondrial membrane protein involved with energy mobilization during oxidative
      phosphorylation. We recently showed that rodent Ant1 is upregulated by
      transforming growth factor-beta (TGF-beta) in reactive astrocytes following CNS
      injury. In the present study, we describe the molecular mechanisms by which TGF
      beta1 regulates Ant1 gene expression in cultured primary rodent astrocytes.
      RESULTS: Transcription reporter analysis verified that TGF-beta1 regulates
      transcription of the mouse Ant1 gene, but not the gene encoding the closely
      related Ant2 isoform. A 69 basepair TGF-beta1 responsive element of the Ant1
      promoter was also identified. Electrophoretic mobility shift assays demonstrated
      that astrocyte nuclear proteins bind to this response element and TGF-beta1
      treatment recruits additional nuclear protein binding to this element. Antibody
      supershift and promoter deletion analyses demonstrated that Sp1 consensus binding
      sites in the RE are important for TGF-beta1 regulation of Ant1 in astrocytes.
      Additionally, we demonstrate that Smad 2, 3 and 4 transcription factors are
      expressed in injured cerebral cortex and in primary astrocyte cultures. TGF-beta1
      activated Smad transcription factors also contribute to Ant1 regulation since
      transcription reporter assays in the presence of dominant negative (DN)-Smads 3
      and 4 significantly reduced induction of Ant1 by TGF-beta1. CONCLUSION: The
      specific regulation of Ant1 by TGF-beta1 in astrocytes involves a cooperative
      interaction of both Smad and Sp1 binding elements located immediately upstream of
      the transcriptional start site. The first report of expression of Smads 2, 3 and
      4 in astrocytes provided here is consistent with a regulation of Ant1 gene
      expression by these transcription factors in reactive astrocytes. Given the
      similarity in TGF-beta1 regulation of Ant1 with other genes that are thought to
      promote neuronal survival, this interaction may represent a general mechanism
      that underlies the neuroprotective effects of TGF-beta1.

PMID- 14720307
TI  - Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and
      chemokine cDNAs.
AB  - BACKGROUND: Sin Nombre virus (SNV) establishes a persistent infection in the deer
      mouse, Peromyscus maniculatus. A strong antibody response occurs in response to
      SNV infection, but the role of the innate immune response is unclear. To address
      this issue, we have initiated an effort to identify and characterize deer mouse
      cytokine and chemokine genes. Such cytokines and chemokines are involved in
      various aspects of immunity, including the transition from innate to adaptive
      responses, type I and type II responses, recruitment of leukocytes to sites of
      infection, and production of mature cells from bone marrow progenitors. RESULTS:
      We established a colony of SNV antibody-negative deer mice and cloned 11 cytokine
      and chemokine partial cDNA sequences using directed PCR. Most of the deer mouse
      sequences were highly conserved with orthologous sequences from other rodent
      species and functional domains were identified in each putative polypeptide.
      CONCLUSIONS: The availability of these sequences will allow the examination of
      the role of these cytokines in deer mouse responses to infection with Sin Nombre
      virus.

PMID- 14720308
TI  - Identification and comparative analysis of components from the signal recognition
      particle in protozoa and fungi.
AB  - BACKGROUND: The signal recognition particle (SRP) is a ribonucleoprotein complex
      responsible for targeting proteins to the ER membrane. The SRP of metazoans is
      well characterized and composed of an RNA molecule and six polypeptides. The
      particle is organized into the S and Alu domains. The Alu domain has a
      translational arrest function and consists of the SRP9 and SRP14 proteins bound
      to the terminal regions of the SRP RNA. So far, our understanding of the SRP and
      its evolution in lower eukaryotes such as protozoa and yeasts has been limited.
      However, genome sequences of such organisms have recently become available, and
      we have now analyzed this information with respect to genes encoding SRP
      components. RESULTS: A number of SRP RNA and SRP protein genes were identified by
      an analysis of genomes of protozoa and fungi. The sequences and secondary
      structures of the Alu portion of the RNA were found to be highly variable.
      Furthermore, proteins SRP9/14 appeared to be absent in certain species.
      Comparative analysis of the SRP RNAs from different Saccharomyces species
      resulted in models which contain features shared between all SRP RNAs, but also a
      new secondary structure element in SRP RNA helix 5. Protein SRP21, previously
      thought to be present only in Saccharomyces, was shown to be a constituent of
      additional fungal genomes. Furthermore, SRP21 was found to be related to metazoan
      and plant SRP9, suggesting that the two proteins are functionally related.
      CONCLUSIONS: Analysis of a number of not previously annotated SRP components show
      that the SRP Alu domain is subject to a more rapid evolution than the other parts
      of the molecule. For instance, the RNA portion is highly variable and the protein
      SRP9 seems to have evolved into the SRP21 protein in fungi. In addition, we
      identified a secondary structure element in the Saccharomyces RNA that has been
      inserted close to the Alu region. Together, these results provide important clues
      as to the structure, function and evolution of SRP.

PMID- 14720309
TI  - Direct selection on male attractiveness and female preference fails to produce a
      response.
AB  - BACKGROUND: Theoretical studies suggest that direct and indirect selection have
      the potential to cause substantial evolutionary change in female mate choice.
      Similarly, sexual selection is considered a strong force in the evolution of male
      attractiveness and the exaggeration of secondary sexual traits. Few studies have,
      however, directly tested how female mate choice and male attractiveness respond
      to selection. Here we report the results of a selection experiment in which we
      selected directly on female mating preference for attractive males and,
      independently, on male attractiveness in the guppy, Poecilia reticulata. We
      measured the direct and correlated responses of female mate choice and male
      attractiveness to selection and the correlated responses of male ornamental
      traits, female fecundity and adult male and female survival. RESULTS:
      Surprisingly, neither female mate choice nor male attractiveness responded
      significantly to direct or to indirect selection. Fecundity did differ
      significantly among lines in a way that suggests a possible sexually-antagonistic
      cost to male attractiveness. CONCLUSIONS: The opportunity for evolutionary change
      in female mate choice and male attractiveness may be much smaller than predicted
      by current theory, and may thus have important consequences for how we understand
      the evolution of female mate choice and male attractiveness. We discuss a number
      of factors that may have constrained the response of female choice and male
      attractiveness to selection, including low heritabilities, low levels of genetic
      (co)variation in the multivariate direction of selection, sexually-antagonistic
      constraint on sexual selection and the "environmental covariance hypothesis".

PMID- 14720310
TI  - Programmed cell death in amyotrophic lateral sclerosis: a mechanism of pathogenic
      and therapeutic importance.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disease of
      adulthood. Mounting evidence indicates that molecular components of the
      programmed cell death (PCD) machinery are implicated in the demise of motor
      neurons in this illness. PCD, rather than being passive, is an active mechanism
      of cell death tightly regulated by multiple molecular pathways. REVIEW SUMMARY:
      Thus far, little is known about the etiology and the pathogenesis of ALS.
      However, several studies support the view that PCD is instrumental in ALS
      neurodegenerative process. Data from postmortem ALS specimens and from
      experimental models of ALS show that some dying motor neurons exhibit features
      reminiscent of apoptosis, a prominent morphologic form of PCD. In addition, many
      key molecular components of the PCD machinery are activated in ALS spinal cords.
      Supporting the significance of these alterations, genetic and pharmacological
      interventions aimed at mitigating these changes prolong survival and attenuate
      neurodegeneration in a mouse model of ALS. CONCLUSIONS: The morphologic evidence
      of PCD in ALS remains an equivocal. However, the molecular evidence of PCD
      involvement in ALS is compelling. Moreover, preclinical studies in mice
      demonstrate the beneficial effects of targeting PCD on ALS-like
      neurodegeneration. The neurologist needs to be familiar with the concept of PCD
      and the potential significance of targeting PCD as neuroprotective strategies for
      ALS.

PMID- 14720311
TI  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a disease of two
      genomes.
AB  - BACKGROUND: Mitochondrial encephalomyopathies are clinically and genetically
      heterogeneous because mitochondria are the products of 2 genomes: mitochondrial
      DNA (mtDNA) and nuclear DNA (nDNA). Among the mendelian-inherited mitochondrial
      diseases are defects of intergenomic communication, disorders due to nDNA
      mutations that cause depletion and multiple deletions of mtDNA. REVIEW SUMMARY:
      Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder of intergenomic communication and is defined clinically by 1)
      severe gastrointestinal dysmotility; 2) cachexia; 3) ptosis, ophthalmoparesis, or
      both; 4) peripheral neuropathy; and 5) leukoencephalopathy. Skeletal muscle
      biopsies of patients have revealed abnormalities of mtDNA and mitochondrial
      respiratory chain enzymes. The disease is caused by mutations in the thymidine
      phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to
      thymine and deoxyribose 1-phosphate. In MNGIE patients, TP enzyme activity is
      reduced drastically, and plasma thymidine and deoxyuridine are elevated
      dramatically. We have hypothesized that alterations of nucleoside metabolism
      cause an imbalanced mitochondrial nucleotide pool that leads to depletion and
      deletions of mtDNA. CONCLUSIONS: MNGIE is a recognizable clinical syndrome caused
      by mutations in TP. The diagnosis can be confirmed by measuring TP activity in
      buffy coat or plasma levels of thymidine and deoxyuridine. Reduction of
      circulating thymidine and deoxyuridine in MNGIE patients may be therapeutic.

PMID- 14720312
TI  - Evaluation and management of medically unexplained physical symptoms.
AB  - BACKGROUND: Medically unexplained physical symptoms (MUPS) and related syndromes
      are common in medical care and the general population, are associated with
      extensive morbidity, and have a large impact on functioning. Much of medical
      practice emphasizes specific pharmacological and surgical intervention for
      discrete disease states. Medical science, with its emphasis on identifying
      etiologically meaningful diseases comprised of homogeneous groups of patients,
      has split MUPS into a number of diagnostic entities or syndromes, each with its
      own hypothesized pathogenesis. However, research suggests these syndromes may be
      more similar than different, sharing extensive phenomenological overlap and
      similar risk factors, treatments, associated morbidities, and prognoses. Examples
      of syndromes consisting of MUPS include chronic fatigue syndrome, fibromyalgia,
      multiple chemical sensitivities, somatoform disorders, and 'Gulf War Syndrome.'
      REVIEW SUMMARY: This paper is a narrative review of the increasing body of
      evidence suggesting that MUPS and related syndromes are common, disabling, and
      costly. It emphasizes that MUPS occur along a continuum of symptom count,
      severity, and duration and may be divided into acute, subacute (or recurrent),
      and chronic types. Predisposing, precipitating, and perpetuating factors
      influence the natural history of MUPS. CONCLUSIONS: Effective symptom management
      involves collaborative doctor-patient approaches for identification of problems
      based on a combination of medical importance and patient readiness to initiate
      behavioral change, negotiated treatment goals and outcomes, gradual physical
      activation and exercise prescription. Additionally, efforts should be made to
      teach and support active rather than passive coping with the symptoms.

PMID- 14720313
TI  - Brain metastases.
AB  - BACKGROUND: Systemic cancer is the second most common cause of death for adults
      in the United States. Twenty percent of these patients develop neurologic
      symptoms sometime during their illness. An apparent increase in the incidence of
      both systemic cancers and resulting brain metastases are posing an increasing
      challenge to health care providers. Neurologic complications lead to significant
      morbidity and mortality in these patients. Therefore, it is important to
      understand the current concepts of diagnosis and treatment of patients with brain
      metastases. REVIEW SUMMARY: This review summarizes the epidemiology, clinical
      features, pathophysiology, and diagnostic evaluation of brain metastases. The
      section on current treatments is presented from the perspective of the three most
      common primary tumor locations along with the treatment approach to other
      metastatic tumors. This review includes a thorough evaluation of the literature,
      highlights controversies over treatment options, and provides insight into novel
      approaches currently under investigation. Clinical studies needed for further
      study are also discussed. CONCLUSIONS: A clearer understanding of the
      pathophysiology of metastatic tumors and advances in diagnostic technology have
      paved the road to a better approach to treatment of brain metastases. Although no
      curative treatments are available to date, significant improvement in a patient's
      quality of life and life expectancy can be achieved with the available therapy. A
      better understanding of different primary cancers leading to brain metastases
      leads to a more effective treatment. More studies are needed to critically
      analyze the clear benefit of these treatment options in selected patients.

PMID- 14720314
TI  - Cannabis use and cerebrovascular disease.
AB  - BACKGROUND: Cannabis is the most commonly abused illicit drug and is often
      considered innocuous. However, cases of acute onset neurologic dysfunction
      occurring in relation to cannabis use have been described and corresponding
      cerebral imaging studies have documented focal ischemic changes and vessel
      abnormalities. REVIEW SUMMARY: This article reviews all reported cases of
      presumed cannabis related cerebral ischemic events in the medical literature, as
      well as pertinent human and animal experimental studies on the cardiovascular and
      cerebrovascular effects of cannabis. CONCLUSIONS: Cannabis use seems to have been
      causally related to several instances of cerebral ischemia and infarction.
      Proposed etiologic mechanisms have included cerebral vasospasm,
      cardioembolization, and systemic hypotension with impaired cerebral
      autoregulation, but most of the available data points to a vasospastic process.
      The exact relation of cannabis to cerebrovascular disease remains to be
      determined.

PMID- 14720315
TI  - 10 most commonly asked questions about obstructive sleep apnea syndrome.

PMID- 14720316
TI  - Patient and family fact sheet. Vagus nerve stimulation.

PMID- 14720317
TI  - Plasma glycine and serine levels in schizophrenia compared to normal controls and
      major depression: relation to negative symptoms.
AB  - Previous studies have suggested decreased N-methyl-D-aspartate (NMDA)-type
      glutamate receptor function may contribute to increased negative symptoms in
      patients with schizophrenia. Consistent with this hypothesis, glycine, a co
      agonist at NMDA receptors, has been reported to improve negative symptoms
      associated with the illness. This study was performed to determine if plasma
      levels of glycine or its ratio to serine, a precursor of glycine, are decreased
      in patients with schizophrenia compared to normal control subjects or patients
      with major depression. We also tested the hypothesis that these amino acids were
      correlated with negative symptoms in subjects with schizophrenia. Plasma levels
      of glycine, serine, and their ratio, were compared in 144 patients with
      schizophrenia, 44 patients with major depression, and 49 normal control subjects.
      All subjects were medication-free. Psychopathology was evaluated using the Brief
      Psychiatric Rating Scale (BPRS). Plasma glycine levels and glycine/serine ratios
      were decreased in patients with schizophrenia relative to control subjects and
      patients with major depression. By contrast, serine levels were increased in
      patients with schizophrenia compared to normal subjects but not compared to major
      depression. Patients with major depression also had increased plasma serine
      levels and decreased glycine/serine ratios compared to normal controls, but
      glycine levels were not different from those of normal controls. In subjects with
      schizophrenia, glycine levels predicted the Withdrawal-Retardation score (BPRS),
      whereas no such correlation was found in subjects with major depression. These
      results provide additional evidence that decreased availability of glycine may be
      related to the pathophysiology of negative symptoms. The decreases in plasma
      glycine levels support the evidence for an abnormality in the glutamatergic
      system in schizophrenia, and provide additional support for efforts to improve
      negative symptoms by augmentation of antipsychotic drugs with agonists at the
      glycine site of the NMDA receptor.

PMID- 14720318
TI  - An autoradiographic study of the influence of pindolol upon [35S]GTPgammaS
      binding in rat, guinea pig and human brain.
AB  - The 5-HT1A/beta-adrenoceptor ligand (+/-)pindolol has been used in clinical
      trials to enhance the antidepressant effect of selective serotonin (5-HT)
      reuptake inhibitors (SSRIs). The accelerating effect of (+/-)pindolol is thought
      to derive from its blockade of the SSRI-induced, 5-HT1A autoreceptor-mediated
      inhibition of serotonergic cell firing and 5-HT release. However, controversial
      results have been reported in regard to its ability to antagonize the effect of 5
      HT at such receptors. In the present study, we have analysed the effect of (+/
      )pindolol on receptor-mediated G-protein activation by measuring guanylyl 5'
      [gamma-[35S]thio]-triphosphate ([35S]GTPgammaS) binding onto tissue sections from
      the hippocampus and dorsal raphe nucleus from rat, guinea pig and human brain. In
      these regions, enriched in 5-HT1A receptors, (+/-)pindolol antagonized the
      stimulation of [35S]GTPgammaS binding induced by 5-HT in a concentration
      dependent manner. We found that in both rat and human brain the calculated pEC50
      values were higher in the dorsal raphe nucleus than in hippocampus. This suggests
      a higher potency of (+/-)pindolol at somatodendritic 5-HT1A receptors compared to
      post-synaptic 5-HT1A sites. In the absence of 5-HT, (+/-)pindolol (up to 10(-3)
      M) did not modify [35S]GTPgammaS binding, which remained at basal levels,
      indicating that, in this assay, (+/-)pindolol acts as a neutral antagonist rather
      than a partial agonist as it has been observed in other experimental models. The
      present data are relevant for the understanding of the neurobiological basis of
      pindolol acceleration of the action of SSRI antidepressants.

PMID- 14720319
TI  - Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by
      cytochromes P450 1A1 and 1B1.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed
      environmental chemicals. PAHs acquire carcinogenicity only after they have been
      activated by xenobiotic-metabolizing enzymes to highly reactive metabolites
      capable of attacking cellular DNA. Cytochrome P450 (CYP) enzymes are central to
      the metabolic activation of these PAHs to epoxide intermediates, which are
      converted with the aid of epoxide hydrolase to the ultimate carcinogens, diol
      epoxides. Historically, CYP1A1 was believed to be the only enzyme that catalyzes
      activation of these procarcinogenic PAHs. However, recent studies have
      established that CYP1B1, a newly identified member of the CYP1 family, plays a
      very important role in the metabolic activation of PAHs. In CYP1B1 gene-knockout
      mice treated with 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene,
      decreased rates of tumor formation were observed, when compared to wild-type
      mice. Significantly, gene expression of CYP1A1 and 1B1 is induced by PAHs and
      polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin through
      the arylhydrocarbon receptor. Differences in the susceptibility of individuals to
      the adverse action of PAHs may, in part, be due to differences in the levels of
      expression of CYP1A1 and 1B1 and to genetic variations in the CYP1A1 and 1B1
      genes.

PMID- 14720320
TI  - Isolation of p53-target genes and their functional analysis.
AB  - Mutations of the p53 gene are the most common genetic alterations found in human
      cancers, and are known to play crucial roles in tumor development and
      progression. The p53 gene encodes a protein functioning as a transcription
      factor, and the biological functions of p53 are manifested through the activities
      of its downstream genes. Identification of these downstream genes involved in the
      p53-signaling pathway should provide more detailed insight into the molecular
      mechanisms that mediate tumor-suppressor activities, as well as various responses
      to cellular stress. We have been attempting to isolate p53-target genes by means
      of various approaches, including differential display, cDNA microarray analysis,
      and direct cloning of the p53-binding sequences from human genomic DNA. Here I
      review our recent work on isolation of p53-target genes and their functional
      analysis. The physiological functions of p53-target genes include apoptosis (GML,
      p53AIP1, and STAG1), DNA repair (p53R2), inhibition of angiogenesis (BAI1), re
      entry into the cell cycle (p53RFP), oxidative stress (CSR), and determination of
      cell fate (p53RDL1).

PMID- 14720321
TI  - Transforming growth factor-beta signaling is differentially inhibited by
      Smad2D450E and Smad3D407E.
AB  - A missense mutant of Smad2, Smad2D450E, that was not phosphorylated by
      transforming growth factor beta (TGF-beta) signaling, was identified in
      colorectal cancer. Previously, we constructed a mutant Smad3, Smad3D407E, which
      has an Asp to Glu mutation in the corresponding position of Smad2D450. Smad3D407E
      was not phosphorylated by the constitutively active form of the TGF-beta type I
      receptor, and inhibited the phosphorylation of co-expressed wild-type Smad2 and
      Smad3. In the present study, we examined the inhibitory effects of Smad2D450E on
      TGF-beta signaling and found that there are considerable differences between
      Smad2D450E and Smad3D407E. Smad2D450E suppressed the phosphorylation of Smad2,
      but did not affect the phosphorylation of Smad3, while Smad3D407E blocked the
      phosphorylation of both Smad2 and Smad3. Consistent with these results,
      Smad2D450E reduced hetero-oligomer formation of Smad2 with Smad4, but not of
      Smad3 with Smad4, while Smad3D407E reduced hetero-oligomer formation of both
      Smad2 and Smad3 with Smad4. However, Smad2D450E reduced the binding of Smad3 to a
      target DNA element as well as Smad2-binding, and Smad2D450E had inhibitory
      effects on the transcriptional activity of several targets, as Smad3D407E did.
      These results suggested that Smad2D450E might block the Smad3-mediated TGF-beta
      signaling in a hitherto unknown manner after the phosphorylation and hetero
      oligomer formation, such as in the process of nuclear translocation or
      transcriptional regulation, which we could not identify previously by using
      Smad3D407E.

PMID- 14720322
TI  - Suppression of metastasis by nuclear factor kappaB inhibitors in an in vivo lung
      metastasis model of chemically induced hepatocellular carcinoma.
AB  - To evaluate the suppressive effects of nuclear factor kappa B (NF-kappaB)
      inhibitors on metastasis, three agents, pentoxifylline (PTX, 0.5% in diet), N
      acetyl-L-cysteine (NAC, 0.5% in diet), and aspirin (ASP, 0.5% in diet) were
      applied in an in vivo highly metastatic rat hepatocellular carcinoma (HCC) model
      in F344 male rats. Administration of NF-kappaB inhibitors for 8 weeks after
      induction of highly metastatic HCC by sequential treatment with
      diethylnitrosamine and N-nitrosomorpholine did not cause any significant change
      in survival rate or body weight. The incidence of HCC was 100% at week 23,
      regardless of treatment with NF-kappaB inhibitors. PTX, NAC, and ASP did not
      exert any significant effect on the development or differentiation of HCCs,
      although PTX tended to decrease the multiplicity of HCC. Although no lung
      metastasis was observed in the rats killed at the end of the period of carcinogen
      exposure, lung metastasis was found in 100% of animals in all the groups at the
      end of the experiment. Multiplicity of lung metastasis was significantly
      decreased by PTX and NAC, whereas ASP was without significant influence. The size
      of metastatic nodules was also significantly reduced in the PTX treatment group.
      Furthermore, the inhibitory kappa-B (IkappaB) protein level, considered to be a
      marker for the degree of NF-kappaB transcription, was significantly suppressed by
      PTX. mRNA expression in HCC for vascular cell adhesion molecule-1 (VCAM-1), which
      is considered to play a key role in attachment of cancer cells to the
      endothelium, was significantly suppressed by PTX. Among the splicing variants of
      VEGF, VEGF-A120, VEGF-A144, VEGF-A164, and VEGF-A188, suppressed mRNA expression
      of VEGF-A188 appeared to be correlated with suppression of lung metastasis
      formation. In conclusion, the present study demonstrated that NF-kappaB
      inhibitors have the potential to inhibit lung metastasis from rat HCCs in vivo,
      and PTX is especially promising. Its mechanism of action may involve suppression
      of VCAM-1 and VEGF-A188 production.

PMID- 14720323
TI  - Inhibition of lymphangiogenesis-related properties of murine lymphatic
      endothelial cells and lymph node metastasis of lung cancer by the matrix
      metalloproteinase inhibitor MMI270.
AB  - Based on a previous report on the effect of a matrix metalloproteinase (MMP)
      inhibitory compound, MMI270, in regulating tumor-induced angiogenesis, as well as
      recent findings concerning functional correlations among tumor metastasis,
      angiogenesis and lymphangiogenesis, we investigated the anti-metastatic efficacy
      of MMI270 in a murine model of lymph node metastasis of lung cancer, and analyzed
      whether this inhibitor could also regulate lymphangiogenesis-related properties
      of murine lymphatic endothelial cells (LECs) and invasive properties of Lewis
      lung cancer (LLC) cells. The observation that MMI270 led to a significant
      decrease in the weight of tumor-metastasized lymph nodes of mice led us to test
      its anti-lymphangiogenic and anti-invasive effects in vitro. Murine LECs were
      characterized by an in vitro tube formation assay, by semi-quantitative RT-PCR
      assay to examine the expression of mRNAs for flt-4, Flk-1, Tie-1, Tie-2,
      CD54/ICAM1, vWF, MMPs and uPA, and by western blotting to confirm the protein
      expression of flt-4 and CD31/PECAM. This is the first report on the expression of
      MMP-2, MMP-9 and MT1-MMP in murine LECs, as well as on the inhibition of their
      enzymatic activity, and of the invasive ability and tube-forming property of LECs
      by an MMP inhibitor. Furthermore, MMI270 was shown to strongly inhibit the
      activity of MMP-2 and -9 produced by LLC cells and the invasion of these cells
      through Matrigel. In summary, the present results indicate that MMI270, apart
      from its anti-tumor angiogenic application, might be useful as an anti-metastatic
      drug, on the basis of its downregulatation of both the lymphangiogenesis-related
      properties of LECs and the invasive properties of LLC cells in vitro.

PMID- 14720324
TI  - Expression of VEGF-C and VEGF-D at the invasive edge correlates with lymph node
      metastasis and prognosis of patients with colorectal carcinoma.
AB  - Vascular endothelial growth factor (VEGF)-C and VEGF-D are potent lymphangiogenic
      factors produced by tumor and stromal cells. The purpose of this study was to
      determine whether expression of VEGF-C and/or VEGF-D correlates with
      clinicopathological features of human colorectal carcinoma. Expression of mRNAs
      for VEGF-C, VEGF-D, and their receptor VEGFR-3 was examined by reverse
      transcription-polymerase chain reaction (RT-PCR) in six colon carcinoma cell
      lines and in fresh endoscopic biopsy specimens from 20 patients with colorectal
      carcinoma. Expression of VEGF-C and VEGF-D protein was also examined
      immunohistochemically in 139 archival surgical specimens of human colorectal
      carcinoma. Of the six cell lines, one (Colo320D) constitutively expressed VEGF-C
      and four (Colo320D, DLD-1, km12sm, km12c) constitutively expressed VEGF-D mRNA.
      Expression of VEGF-D mRNA was increased under low oxygen conditions, and all six
      cell lines constitutively expressed VEGF-D mRNA under hypoxic conditions. Of the
      139 specimens of human colorectal carcinoma, 65 (46.8%) showed intense VEGF-C
      immunoreactivity and 41 (29.5%) showed intense VEGF-D immunoreactivity. In 49
      (75.3%) of the 65 and 20 (48.8%) of the 41 cases, heterogeneous intratumoral
      staining was observed for VEGF-C and VEGF-D, respectively, with the highest
      levels of expression at the invasive edges. VEGF-C expression correlated with the
      depth of tumor invasion, lymphatic involvement, venous involvement, lymph node
      metastasis, and liver metastasis, and VEGF-D expression correlated with the depth
      of tumor invasion, lymph node metastasis, and liver metastasis. No correlation
      was observed between VEGF-C and VEGF-D expression in tumors. The survival time of
      patients with VEGF-C-positive tumors was significantly shorter than that of
      patients with VEGF-C-negative tumors, and the survival time of patients with VEGF
      D-positive tumors was significantly shorter than that of patients with VEGF-D
      negative tumors. The survival time of patients with both VEGF-C- and VEGF-D
      positive tumors was significantly shorter than that of patients with both VEGF-C-
      and VEGF-D-negative tumors. These results suggest that VEGF-C and VEGF-D may be
      independent and important prognostic factors in patients with human colorectal
      carcinoma.

PMID- 14720325
TI  - Promoter methylation status and expression of TMS1 gene in human epithelial
      ovarian cancer.
AB  - Gene silencing associated with aberrant DNA methylation of promoter CpG islands
      is one mechanism through which tumor suppressor genes are inactivated in human
      cancers. TMS1 (target of methylation-induced silencing) is a CpG island
      associated gene that functions in the regulation of apoptosis. In this study, we
      examined the DNA methylation status of the TMS1 promoter in ovarian cancer cell
      lines and tissues by methylation-specific PCR (MSP) and its mRNA expression by
      reverse transcription and quantitative PCR. Aberrant methylation of TMS1 was
      present in 7/12 ovarian cancer cell lines and 8/20 primary ovarian cancer
      tissues. The median value of relative TMS1 gene expression in cancers with
      methylation (0.15) was significantly lower than that in cancers without
      methylation (13.9) (P < 0.001). The expression of the TMS1 gene was relatively
      high (48.5) in the normal ovarian cDNA library. TMS1 gene expression was restored
      by treatment with the demethylating agent 5-aza-2'-deoxycitidine in the OV90 cell
      line, which lacks the TMS1 transcript. Our results suggest that aberrant
      methylation of TMS1 may play a role in the pathogenesis of ovarian cancer.

PMID- 14720326
TI  - Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric
      cancer patients.
AB  - Survivin, a member of the inhibitor-of-apoptosis family, inhibits apoptosis by
      blocking caspase-3 and -7 activation. Gastric cancer, which is among the most
      intractable of malignant tumors, is known for resistance to various drugs,
      including cis-diamminedichloroplatinum (CDDP). Since this agent induces apoptosis
      via caspase-3 activation, survivin may mediate the drug resistance. We
      investigated survivin messenger RNA (mRNA) expression in gastric cancers and the
      relationship between expression and sensitivity to CDDP. Expression of the
      survivin gene was significantly up-regulated in gastric cancers compared to the
      tissues of normal mucosa, atrophic gastritis, and intestinal metaplasia (P <
      0.0001) as assessed by a quantitative reverse transcription-polymerase chain
      reaction (RT-PCR), and was negatively associated with overall survival of
      patients who received CDDP-based chemotherapy. To investigate whether survivin is
      a resistance factor against CDDP-induced apoptosis, we transfected wild-type and
      dominant-negative mutants of the survivin gene into gastric cancer cells using a
      lipofection method. Overexpression of survivin protected MKN45 cells from CDDP
      induced apoptosis. Expression of the dominant-negative mutant of the survivin
      gene sensitized NUGC-3 cells to drug-induced apoptosis. These results indicate
      that survivin may be pivotal in the development of gastric cancer and resistance
      to CDDP, and therefore controlling expression of the survivin gene may be
      therapeutically useful.

PMID- 14720327
TI  - Nemo-like kinase suppresses a wide range of transcription factors, including
      nuclear factor-kappaB.
AB  - Nemo-like kinase (NLK) is a serine/threonine kinase that suppresses the
      transcription activity of the beta-catenin-T-cell factor (TCF) complex through
      phosphorylation of TCF. Our previous study showed that NLK overexpression induces
      apoptosis in DLD-1 human colon cancer cells and that apoptosis induction
      presumably requires a mechanism other than the suppression of beta-catenin-TCF
      complex. Luciferase reporter gene assay with pNF-kappaB-Luc revealed that NLK
      could suppress transcription activity of NF-kappaB in a kinase-dependent manner.
      However, it appeared that transcription co-activators of NF-kappaB, such as CREB
      binding protein (CBP)/p300, were likely to be the direct targets of NLK, rather
      than NF-kappaB itself. Luciferase reporter gene analysis of GAL4-CBP fusion
      proteins revealed that the C-terminal region of CBP was critical for
      transcription suppression by NLK. In vitro kinase assay showed that NLK could
      phosphorylate the C-terminal domain of CBP. However, HAT activity was not
      suppressed by the induction of wild-type NLK in DLD-1 cells. Furthermore, we
      observed that NLK suppressed the transcription activity of AP-1, Smad, and p53,
      all of which also utilize CBP as a co-activator. The extent of suppression by NLK
      was similar among the transcription factors tested (50-60% reduction). Our
      results suggest that NLK may suppress a wide range of gene expression, possibly
      through CBP.

PMID- 14720328
TI  - Frequent hypomethylation in multiple promoter CpG islands is associated with
      global hypomethylation, but not with frequent promoter hypermethylation.
AB  - Hypomethylation of the global genome, considered to be composed mainly of
      repetitive sequences, is consistently observed in cancers, and aberrant hypo- and
      hypermethylation of CpG islands (CGIs) in promoter regions are also observed.
      Since methylation alterations in unique promoter sequences and in other genomic
      regions have distinct consequences, we analyzed the relationship between the
      global hypomethylation and the hypomethylation of unique promoter CGIs using
      human gastric cancers. Seven of ten gastric cancer cell lines showed marked
      decreases in 5-methylcytosine content, which correlated with hypomethylation of
      the LINE1 repetitive sequence. Six of the seven cell lines showed hypomethylation
      in five or all of the six normally methylated CGIs in promoter regions of six
      genes, and this was associated with induction of aberrant expression. The
      remaining three cell lines without global hypomethylation showed promoter
      hypomethylation in one or none of the six CGIs. Frequent promoter
      hypomethylation, however, did not correlate with frequent promoter
      hypermethylation. In primary gastric cancers too, global hypomethylation was
      associated with hypomethylation of LINE1 repetitive sequence and promoter
      hypomethylation. Of 93 gastric cancers, 33 cancers with frequent promoter
      hypomethylation and 27 cancers with frequent promoter hypermethylation
      constituted different groups. These findings represent experimental evidence that
      frequent hypomethylation of normally methylated promoter CGIs is associated with
      global hypomethylation, and that these hypomethylations occur independently of
      frequent promoter CGI hypermethylation.

PMID- 14720329
TI  - Serum phytoestrogens and prostate cancer risk in a nested case-control study
      among Japanese men.
AB  - The purpose of this study was to examine whether a high serum concentration of
      phytoestrogens reduces the risk of prostate cancer in a case-control study nested
      in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study).
      Information on lifestyles and sera of the subjects were collected in 1988-90, and
      they were followed up to 1999. Incident and dead cases of prostate cancer and
      controls were matched for study area and age. Phytoestrogens and sex hormones in
      sera stored at - 80 degrees C were measured in 2002. Of 14,105 male subjects of
      the cohort who donated their sera, 52 cases and 151 controls were identified.
      Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after
      excluding subjects with low testosterone levels who were suspected of having had
      medical intervention, and 3) 28 cases and 69 controls with prostate specific
      antigen level of </= 10.0 ng/ml. The odds ratio (OR) for the highest level to the
      lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41
      (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second
      dataset. Genistein and daidzein showed similar findings in the third one. Equol
      and equol/daidzein ratio showed consistent findings in all three datasets (OR =
      0.39, 95% CI; 0.13, 0.89, trend P = 0.02 for the first dataset). Their effects
      seemed to be independent of serum sex hormones. In conclusion, serum genistein,
      daidzein, and equol seemed to dose-dependently reduce prostate cancer risk.

PMID- 14720330
TI  - Relation of cigarette smoking and alcohol use to colorectal adenomas by subsite:
      the self-defense forces health study.
AB  - While smoking has consistently been shown to be related to increased risk of
      colorectal adenomas, few studies have addressed the association between smoking
      and site-specific colorectal adenomas. The reported association between alcohol
      use and colorectal adenomas has been inconsistent. We evaluated risks of adenomas
      at the proximal colon, distal colon, and rectum in relation to cigarette smoking
      and alcohol use, and their interaction. Subjects were 754 cases with
      histologically proven colorectal adenomas and 1547 controls with normal
      colonoscopy among male officials of the Self-Defense Forces (SDF) undergoing
      total colonoscopy at two SDF hospitals. Statistical adjustment was made for
      hospital, rank, body mass index, physical activity, and either smoking or alcohol
      drinking. Cigarette smoking was significantly associated with an increased risk
      of adenomas, regardless of the location of the adenomas, but the increased risk
      associated with smoking was more pronounced for rectal adenomas. Alcohol use was
      associated with moderately increased risks of distal colon and rectal adenomas,
      but not of proximal colon adenomas. Cigarette smoking, but not alcohol drinking,
      was associated with greater increases in the risk of large adenomas and of
      multiple adenomas across the colorectum. There was no measurable interaction of
      cigarette smoking and alcohol drinking on colorectal adenomas. The findings
      corroborate an increased risk of colorectal adenomas associated with smoking and
      a weak association between alcohol use and colorectal adenomas. Further studies
      are needed to confirm whether smoking is more strongly related to rectal
      adenomas, large adenomas, or multiple adenomas.

PMID- 14720331
TI  - Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with
      metastatic hormone-refractory prostate cancer.
AB  - To evaluate the safety and toxicity of peptide vaccination for patients with
      metastatic hormone-refractory prostate cancer (HRPC) based on pre-existing
      peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the circulation, 10
      patients positive for human leukocyte antigen (HLA)-A2 with metastatic HRPC were
      enrolled in a phase I study. Peptide-specific CTL-precursors reactive to 16 kinds
      of vaccine candidates in the pre-vaccination peripheral blood mononuclear cells
      (PBMCs) were measured, and patients were followed by vaccination with only
      positive peptides (up to 4 kinds of peptides). Serum prostate-specific antigen
      (PSA) levels were monitored regularly. The peptide vaccination was safe and well
      tolerated with no major adverse effects. The most common toxicities were
      dermatologic reactions at the injection site. Increased CTL response to peptides
      was observed in 4 of 10 patients. Anti-peptide IgG was also detected in post
      vaccination sera of 7 of 10 patients. One patient showed the disappearance of a
      pelvic bone metastasis after five vaccinations. Three patients showed a decrease
      of serum PSA level from the baseline after the vaccination, but no patients
      showed a serum PSA level decrease of >/= 50%. The median survival duration of
      study patients was 22 months with follow-up from 3 to 27 months. We consider that
      the increase in cellular and humoral immune responses, and decrease in PSA level
      in some patients justify further development of peptide vaccination for
      metastatic HRPC patients.

PMID- 14720332
TI  - Vaccination with autologous endothelium inhibits angiogenesis and metastasis of
      colon cancer through autoimmunity.
AB  - Overcoming immune tolerance of tumor angiogenesis should be useful for adjuvant
      therapy of cancer. We hypothesized that vaccination with autologous endothelium
      would induce an autoimmune response targeting tumor angiogenesis. To test this
      concept, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine
      hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of Colon
      26 cancer. Vaccination with autologous HSEs induced both preventive and
      therapeutic anti-tumor immunity that significantly inhibited the development of
      metastases. ELISA revealed an immunoglobulin response involving IgM and IgG
      subclasses. These antibodies had a strong affinity for antigens of both murine
      and human endothelium, and lyzed endothelial cells in the CDC assay. Flow
      cytometry and chromium-release cytotoxicity assay revealed a specific CTL
      response against endothelial cells, which were lyzed in an effector: target ratio
      dependent manner. Neither antibodies nor CTLs reacted with Colon-26. The effect
      of autologous HSEs was more pronounced than that of xenogeneic human umbilical
      vein endothelial cells (HUVECs), which were tested in the same experimental
      setting. Our results suggest that vaccination with autologous endothelium can
      overcome peripheral tolerance of self-angiogenic antigens and therefore should be
      useful for adjuvant immunotherapy of cancer.

PMID- 14720333
TI  - Adenovirus-mediated p53AIP1 gene transfer as a new strategy for treatment of p53
      resistant tumors.
AB  - The p53AIP1 gene, which we recently identified as a novel p53-target, mediates
      p53-dependent apoptosis. We evaluated the effects of adenovirus-mediated
      introduction of p53AIP1 (Ad-p53AIP1) on 30 human cancer-cell lines in vitro, and
      two cell lines in vivo, in comparison with the effects of p53 (Ad-p53). In 20 of
      the 30 cell lines, p53AIP1-induced apoptosis was observed, and in 12 of these
      p53AIP1-sensitive cancer cell lines, the apoptotic effects of p53AIP1 were
      greater than those of p53 itself. Cancers with wild-type p53, which were thought
      to be p53-resistant, were likely to be sensitive to p53AIP1-induced apoptosis.
      p53-resistant cancers such as LS174T (p53 +/+) and A549 (p53 +/+), in which no
      increase of p53AIP1 mRNA expression was observed when Ad-p53 was introduced, were
      killed effectively by Ad-p53AIP1. Furthermore, co-introduction of p53 and p53AIP1
      had a synergistic effect on the induction of apoptosis, regardless of p53 status.
      Finally, adenovirus-mediated introduction of p53AIP1 suppressed tumor growth in
      vivo. These results suggested that p53AIP1 gene transfer might become a new
      strategy for the treatment of p53-resistant cancers.

PMID- 14720334
TI  - Intratumoral injection of IL-2-activated NK cells enhances the antitumor effect
      of intradermally injected paraformaldehyde-fixed tumor vaccine in a rat
      intracranial brain tumor model.
AB  - Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK
      cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were
      inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at
      the basal ganglia of the right hemisphere (intracranial tumor model). Rats were
      intradermally injected three times with vaccine comprising fixed 9L cells, IL-2-
      and GMCSF-microparticles, and tuberculin prior to (protective studies) or after
      (therapeutic studies) challenge with live 9L cells. In the protective studies,
      the vaccine alone achieved significant tumor growth inhibition and elongation of
      mean life span in both the subcutaneous and intracranial tumor models. No
      therapeutic effect was observed in the intracranial tumor model with the vaccine
      alone. However, intratumoral injection of rat NK cells strongly assisted the
      therapeutic effect of the vaccine in the brain tumor model and resulted in a
      statistically significant elongation of life span. We propose that intratumoral
      injection of NK cells may not only kill brain tumor cells directly, but also
      trigger a strong immune response in the focal lesion of the brain after
      vaccination.

PMID- 14720335
TI  - Newer cytotoxic and targeted agents are advancing the treatment of lung cancer.

PMID- 14720336
TI  - The emerging role of gemcitabine in combination with radiation in locally
      advanced, unresectable non-small-cell lung cancer.
AB  - The median survival for patients with locally advanced non-small-cell lung cancer
      (NSCLC) remains 18 months, at best, in cooperative group efforts. Integrating new
      agents into the standard combined modality treatment paradigm is a daunting
      challenge. Gemcitabine has activity in advanced NSCLC and is a potent
      radiosensitizer, but preclinical trials did not delineate an optimal dose or
      schedule, and early attempts to graft full-dose gemcitabine (1000 mg/m2/week)
      onto standard radical thoracic radiation therapy (RT) were marked by significant
      grade 4 and 5 toxicity. More recent trials, however, have shown that attenuated
      doses of 150-300 mg/m2/week during radiation (XRT) are safer and potentially
      efficacious. Higher doses produce dose-limiting esophageal and pulmonary
      toxicities. Using a twice-weekly schedule, the maximum tolerated dose is 35
      mg/m2. The use of 3 dimensional conformal RT may enable significant dose
      escalations while substantially reducing esophageal exposure and minimizing
      toxicity. The cooperative oncology groups are just beginning to evaluate
      gemcitabine in this setting. Cancer and Leukemia Group B, in a randomized phase
      II study, assessed combination gemcitabine and cisplatin in both the induction
      and radiosensitizing setting. During the induction phase, gemcitabine was given
      1250 mg/m2 on days 1 and 8 every 3 weeks for 2 cycles in combination with
      cisplatin 80 mg/m2 every 3 weeks, and then reduced to 600 mg/m2 days 1 and 8
      every 3 weeks during XRT. The overall response rate was 63% with median survival
      of 18.3 months and 1-year and 3-year survival rates of 68% and 28%, respectively.
      Radiation Therapy Oncology Group is currently spearheading a phase I study of
      concurrent radiation and weekly gemcitabine in combination with either weekly
      carboplatin or paclitaxel. Ongoing efforts will also evaluate the role of
      gemcitabine either alone or in combination with docetaxel in the consolidation
      setting after definitive chemoradiation has been completed. Whether gemcitabine
      in combination with radiation, with or without other agents, will ultimately
      prove superior to standard chemoradiation regimens remains to be determined.

PMID- 14720337
TI  - Gemcitabine-based combinations as preoperative therapy in resectable non-small
      cell lung cancer.
AB  - Surgical resection remains the standard of care in early-stage non-small-cell
      lung cancer (NSCLC). In those patients undergoing complete surgical resection,
      the dominant recurrence pattern is systemic with only a minority of patients
      experiencing local recurrence. Unfortunately, adjuvant chemotherapy (with or
      without thoracic radiation therapy) has not been proven to enhance survival in
      resected NSCLC. Preoperative or induction therapy offers several advantages over
      postoperative therapy, including earlier attention to systemic micrometastatic
      disease and enhanced tolerance to treatment. The feasibility of this approach has
      been demonstrated in several phase II as well as phase III trials predominantly
      in stage III NSCLC but also in stage IB and II NSCLC. In proof-of-concept phase
      III trials, the impact preoperative therapy has on survival has not been
      consistent, but most trials are small in patient number, limiting the power they
      have in detecting small but clinically meaningful differences. Gemcitabine
      containing regimens have been evaluated in several phase II trials in resectable
      stage III NSCLC. The overall response rate has ranged from 53%-70% with the
      majority of patients undergoing complete surgical resection. Toxicity has been
      acceptable, and the combination of cisplatin/gemcitabine is currently being
      evaluated as induction therapy in several phase III trials. Ongoing trials in
      stage I-II NSCLC are incorporating gemcitabine-containing regimens in the
      preoperative setting. Continued evaluation of gemcitabine-containing regimens as
      preoperative therapy is warranted given their level of activity and tolerability
      in advanced NSCLC.

PMID- 14720338
TI  - New agents in the treatment of small-cell lung cancer: focus on gemcitabine.
AB  - Small-cell lung cancer (SCLC) accounts for 20%-25% of all new cases of lung
      cancer and represents the sixth most commonly diagnosed cancer in the United
      States. Given the tumor's systemic nature and chemoresponsiveness, chemotherapy
      has become the cornerstone of its management. Chemotherapy significantly prolongs
      survival; however, most of the patients still die within 2 years of diagnosis.
      Combination chemotherapy represents the treatment of choice for this disease. In
      the United States, cisplatin/etoposide is the regimen most frequently used for
      the first-line therapy of SCLC patients because of its better therapeutic index.
      Upon recurrence, topotecan is the Food and Drug Administration-approved treatment
      based on a phase III trial that showed no statistically significant differences
      in survival or response for topotecan compared with CAV
      (cyclophosphamide/doxorubicin/vincristine) but a better disease-related symptom
      improvement compared to baseline favoring the topoisomerase I inhibitor. Newer
      agents, with novel mechanisms of action, have shown activity against SCLC and are
      being tested in many different combinations. Among these agents, gemcitabine has
      attractive mechanisms of action and toxicity profile. Gemcitabine is a pyrimidine
      nucleoside antimetabolite, analogue to cytosine arabinoside, which through
      incorporation into the DNA leads to inhibition of DNA synthesis and cytotoxicity.
      As a single agent, gemcitabine has modest activity against SCLC. However, like
      with many other drugs, response rates improve when gemcitabine is used in
      combination regimens. Phase II and III studies of combinations with classic drugs
      for the management of SCLC patients such as cisplatin and/or etoposide and
      gemcitabine demonstrate comparable results to those of standard therapies. The
      gemcitabine/paclitaxel and gemcitabine/topoisomerase I inhibitor combinations are
      also of great interest, and preliminary results in previously treated patients
      are promising. The proper role of gemcitabine in the treatment of patients with
      SCLC awaits future testing in randomized phase III trials.

PMID- 14720339
TI  - Current data with pemetrexed (Alimta) in non-small-cell lung cancer.
AB  - Pemetrexed (Alimta ) is a novel multitargeted antifolate that inhibits 3 enzymes
      involved in folate metabolism and purine and pyrimidine synthesis. These enzymes
      are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide
      formyltransferase. This agent has broad antitumor activity in phase II trials in
      a wide variety of solid tumors. In non-small-cell lung cancer (NSCLC), single
      agent activity has been documented in the first- and second-line settings.
      Promising activity has also been demonstrated when pemetrexed is combined with
      cisplatin and gemcitabine. A pivotal phase III study in mesothelioma has been
      presented, indicating the superiority of pemetrexed in combination with cisplatin
      versus cisplatin alone in this disease. Approval for pemetrexed in combination
      with cisplatin in advanced mesothelioma is expected within the next 12 months.
      This review discusses the activity of pemetrexed in NSCLC.

PMID- 14720340
TI  - Antisense oligonucleotides in the treatment of non-small-cell lung cancer.
AB  - Antisense oligonucleotides (ASONs) are one of the new classes of molecularly
      targeted agents that have transitioned from the laboratory into clinical trials.
      Rational drug design has resulted in agents directed against a number of
      important cellular targets, including the mRNA of bcl-2, protein kinase (PK) C
      alpha, PKA-I, H-ras, c-raf, R1 and R2 subunit of ribonucleotide reductase, and
      transforming growth factor beta2. These drugs are well tolerated with favorable
      toxicity profiles, and preliminary studies have demonstrated that they can be
      feasibly combined with chemotherapy. Plasma half-life is short, generally
      necessitating continuous prolonged intravenous infusion. Shorter administration
      schedules are being investigated. Efficacy has been demonstrated in early-phase
      studies in non-small-cell lung cancer (NSCLC), non-Hodgkin's lymphoma, ovarian
      cancer, melanoma, and prostate cancer. Molecular correlative studies with
      peripheral blood mononuclear cells and tumor tissue have demonstrated suppression
      of target proteins, suggesting that these drugs are indeed reaching the target.
      Here we discuss the current status of development of ASONs, focusing on LY900003
      (formerly ISIS 3521), an agent directed against PKC-alpha currently under study
      in NSCLC. Phase III studies will determine the ultimate role these agents will
      play in the treatment of cancer. Future areas of study include combination with
      radiation and other molecularly targeted agents, alternative dosing schedules,
      liposomal administration, and the development of new antisense agents directed
      against additional molecular targets.

PMID- 14720341
TI  - Docetaxel/platinum in advanced non-small-cell lung cancer: recent randomized
      trials.
AB  - The role of docetaxel-containing doublets as first-line chemotherapy for patients
      with advanced and metastatic non-small-cell lung cancer (NSCLC) was evaluated in
      a large randomized trial. Docetaxel/cisplatin and docetaxel/carboplatin were
      compared with the reference regimen of vinorelbine/cisplatin. After adjustment
      for imbalances in prognostic factors, the overall survival of patients treated
      with docetaxel/cisplatin was significantly better than that of patients treated
      with vinorelbine/cisplatin, the reference regimen. Survival for patients on the
      docetaxel/carboplatin arm was noninferior to the same reference regimen. The
      major grade 3/4 hematologic toxicity was neutropenia, which affected
      approximately three fourths of the participants. Overall, the docetaxel/platinum
      arms were well tolerated. Both docetaxel/carboplatin and docetaxel/cisplatin
      appear to be effective first-line chemotherapy combinations for advanced NSCLC
      and are efficacious treatment options in this setting. The future of NSCLC
      therapy might lie in the development of novel treatment paradigms that involve
      the integration of targeted agents with traditional cytotoxic chemotherapy.

PMID- 14720342
TI  - The role of docetaxel in nonplatinum-based combination chemotherapy for non-small
      cell lung cancer.
AB  - A number of newer chemotherapeutic agents including docetaxel, gemcitabine,
      irinotecan, and vinorelbine have demonstrated substantial activity in the
      treatment of non-small-cell lung cancer (NSCLC). Their palliative role as single
      agents and in combination with platinum has been well defined in NSCLC. More
      recently, combining these agents without platinum has been the primary objective
      of numerous worldwide clinical trials. Two of these docetaxel/nonplatinum-based
      combinations have demonstrated comparable activity to platinum-based regimens in
      randomized trials. While platinum-based chemotherapy remains an important therapy
      for treatment of NSCLC, nonplatinum combinations may be a reasonable alternative
      for patients. These docetaxel/nonplatinum combinations warrant further evaluation
      in randomized trials to define their optimal role as standard therapy for NSCLC.

PMID- 14720343
TI  - The role of weekly docetaxel in the treatment of advanced non-small-cell lung
      cancer.
AB  - Docetaxel is one of the most active single agents in the treatment of advanced
      non-small-cell lung cancer (NSCLC). Weekly administration of docetaxel markedly
      reduces myelosuppression and also reduces nonhematologic toxicity. Phase II
      trials with single-agent weekly docetaxel have been completed in first- and
      second-line treatment of advanced NSCLC; preliminary results of treatment with
      weekly docetaxel-based combination regimens are also available. In patients who
      were elderly or had poor performance status, weekly docetaxel produced a 19%
      response rate, 28% 1-year survival, and was well tolerated. As second-line
      therapy, response rates to weekly docetaxel were similar to results with
      administration every 3 weeks, although no direct comparisons exist. Combination
      regimens, particularly weekly docetaxel/gemcitabine, also appear active and well
      tolerated and should be further evaluated. Addition of various targeted agents
      (eg, epidermal growth factor receptor inhibitors, antiangiogenesis agents) also
      merits evaluation.

PMID- 14720344
TI  - Docetaxel in second-line treatment of non-small-cell lung cancer.
AB  - The survival and quality-of-life benefits of docetaxel in the second-line
      treatment of non-small-cell lung cancer (NSCLC) are supported by two phase III
      trials: TAX 317 and TAX 320. In TAX 317, 204 patients were randomized to receive
      either docetaxel 100 mg/m2 (D100) or 75 mg/m2 (D75) intravenously every 3 weeks,
      or best supportive care (BSC). Median survival was 9.0 months with D75 versus 4.6
      months for BSC (P = 0.016); 1-year survival was 40% for D75 versus 16% for BSC (P
      = 0.016). Quality-of-life analysis showed significant improvement in several
      disease-related symptoms in patients who received docetaxel. TAX 320 was a
      supportive trial, in which 373 patients were randomized to receive D100, D75, or
      the control treatment of vinorelbine or ifosfamide (V/I). The partial response
      rate was 12% with D100 and 8% with D75 versus 1% with V/I (D100, P = 0.001 and
      D75, P = 0.036). Median response duration was 7+ months. One-year survival was
      32% with D75 and 19% with V/I (P = 0.025). In TAX 320, prior paclitaxel exposure
      had no bearing on the response rate and survival advantage of second-line
      treatment with docetaxel. Response rates to docetaxel were equivalent in the
      cohort of patients who had received prior paclitaxel (10.5%) and the group of
      patients who had not received prior paclitaxel (8.5%). Furthermore, 1-year
      survival rates for patients with no prior paclitaxel therapy were 33% (D75) and
      20% (V/I); 1-year survival rates for patients who had received prior paclitaxel
      were 30% (D75) and 17% (V/I). Docetaxel at a dose of 75 mg/m2 every 3 weeks
      offers a clinically meaningful improvement in response rate, time to progression,
      survival, and quality of life in the second-line treatment of advanced NSCLC.
      Furthermore, prior paclitaxel did not decrease the likelihood of response to
      docetaxel, nor did it lessen the survival advantage seen with docetaxel.

PMID- 14720345
TI  - Docetaxel/radiation combinations: rationale and preclinical findings.
AB  - Concurrent chemoradiotherapy, administration of chemotherapeutic agents during
      the course of radiation therapy, has increasingly been used for treatment of
      advanced locoregional cancer. Improvements in radiation therapy are achieved
      through independent cytotoxic action of drugs and their ability to sensitize
      tumor cells to radiation. Laboratory investigations showed that docetaxel is
      potent in both of these actions. The drug increased the radiosensitivity of in
      vitro cultured cells and the in vivo tumor radioresponse. In contrast to exerting
      a strong enhancement of tumor radioresponse, the ability of docetaxel to modify
      normal tissue radiation damage was much lower. Thus, docetaxel can significantly
      increase therapeutic gain when combined with radiation therapy. The initial
      rationale for using docetaxel and other taxanes as radiation enhancers was the
      ability of these agents to arrest cells in the radiosensitive G2/M phases of the
      cell cycle. Additional mechanisms were subsequently detected, including the
      ability of docetaxel to eliminate radioresistant S-phase cells, cause tumor
      reoxygenation, stimulate antitumor immune resistance mechanisms, and possibly
      inhibit tumor angiogenesis. Because combined chemoradiotherapy treatments are
      limited by normal tissue toxicity, additional treatment strategies are needed to
      improve the antitumor efficacy and to minimize normal tissue toxicity. In this
      regard, many research avenues are being explored, particularly the possibility of
      combining chemoradiotherapy with molecular targeting. This overview addresses the
      rationale for major findings on the interaction of docetaxel and radiation in
      preclinical models and discusses how these findings may impact practical use of
      chemoradiotherapy.

PMID- 14720346
TI  - Concurrent docetaxel and thoracic radiation in non-small-cell lung cancer.
AB  - Locally advanced (stages IIIA and IIIB) non-small-cell lung cancer (NSCLC)
      represents approximately 25% of new cases of NSCLC diagnosed annually. The
      treatment strategy for these patients involves combined-modality therapy with
      chemotherapy and thoracic radiation. Furthermore, a subset of patients with stage
      IIIA disease undergo surgical resection. Docetaxel is a chemotherapy agent with
      activity in both first- and second-line treatment of patients with advanced
      NSCLC. Several recent studies have also incorporated docetaxel in the treatment
      of patients with stage III NSCLC as neoadjuvant therapy, alone or in combination
      with cisplatin or carboplatin and thoracic radiation. Docetaxel has also been
      used as consolidation therapy. This review will summarize the data to date on the
      use of docetaxel and thoracic radiation in the treatment of patients with stage
      III NSCLC.

PMID- 14720347
TI  - Concurrent chemoradiation strategies in the management of unresectable stage III
      non-small-cell lung cancer.
AB  - Locally advanced or unresectable stage III non-small-cell lung cancer (NSCLC)
      patients treated with combined-modality therapy with chemotherapy plus thoracic
      radiation have improved survival compared to those treated with radiotherapy
      alone. Furthermore, recent studies in good performance status, stage III patients
      have shown that concurrent chemoradiotherapy improves survival compared to
      sequential chemoradiotherapy. However, the optimal chemoradiation approach
      continues to evolve and is the subject of this review. Since the majority of
      patients completing chemoradiotherapy will succumb to distant metastatic disease,
      active systemic agents targeting this tumor compartment are required. Recent data
      suggest that full-dose chemotherapy designed to eradicate distant micrometastases
      given either as induction or consolidation has the potential to yield improved
      patient outcomes. Many of these chemotherapeutic agents are also potent
      radiosensitizers, hence providing enhanced local control. The integration of
      these chemotherapeutic agents into chemoradiotherapy programs in stage III NSCLC
      is the focus of current trials. Ongoing research with novel therapeutic agents
      with activity against distant micrometastases, refined radiation techniques, and
      enhanced imaging methodologies to aid in accurate staging are being pursued and
      should lead to improved survival and toxicity outcomes in this disease.

PMID- 14720348
TI  - Chemotherapy regimens in advanced non-small-cell lung cancer: recent randomized
      trials.
AB  - Since the 1980s, cisplatin therapy for advanced non-small-cell lung cancer
      (NSCLC) has shown improvement in patient outcome with respect to overall
      survival. In the past decade, several new agents, such as the taxanes (paclitaxel
      and docetaxel), gemcitabine, vinorelbine, and irinotecan, have also shown
      promising single-agent efficacy in the treatment of advanced NSCLC. Superior
      efficacy was observed when these 5 agents were used in combination with cisplatin
      as compared to cisplatin alone for treatment of patients with NSCLC. The toxicity
      profiles of these 5 agents were found to be largely nonoverlapping with
      cisplatin. The results of recent randomized trials with different cisplatin-based
      chemotherapy regimens have shown that platinum-based therapy is still the
      mainstay for treatment of NSCLC; however, it appears that a chemotherapy efficacy
      plateau has been reached. Moreover, it has also been shown that for patients
      unable to tolerate cisplatin, nonplatinum doublets consisting of gemcitabine with
      either taxanes or vinorelbine are equivalent in efficacy and can be alternatives
      for first-line treatment of advanced NSCLC. Thus, the development of new and
      novel strategies is essential for treatment of NSCLC patients. Ongoing trials
      with vaccines, signal transduction modulators, antiangiogenic agents, and gene
      therapy in combination with chemotherapy

PMID- 14720349
TI  - Gemcitabine-based doublets for advanced non-small-cell lung cancer: beyond
      gemcitabine/cisplatin.
AB  - Gemcitabine is one of the most active agents in the treatment of patients with
      advanced non-small-cell lung cancer (NSCLC). Recent evidence indicates that
      gemcitabine/cisplatin is among the most active doublets in advanced NSCLC, but
      the problem of what to give patients who cannot tolerate cisplatin still remains.
      The combination of gemcitabine/carboplatin is under investigation. Initially
      thought to be too myelosuppressive, recent schedule modifications have made this
      a more feasible doublet for NSCLC. Nonplatinum doublets consisting of gemcitabine
      with the taxanes or vinorelbine are also under investigation. This review covers
      the most current trials of gemcitabine-based doublets in advanced NSCLC.

PMID- 14720350
TI  - Combined-modality therapy for inoperable non-small-cell lung cancer using
      gemcitabine.
AB  - Combined-modality therapy with chemotherapy and radiation appears to be the most
      efficacious therapeutic modality for patients with locally advanced non-small
      cell lung cancer. Most of the trials exploring this approach have utilized older
      agents such as cisplatin, vinblastine, and etoposide. Recent data suggest that
      gemcitabine may be superior to these agents therapeutically, with the ability to
      produce similar or improved outcomes and a milder overall toxicity profile.
      Moreover, gemcitabine is able to sensitize tumor cells to radiation-induced
      apoptosis as well as lead to induction of cells in the radioresistant S phase of
      the cell cycle. These results have suggested that gemcitabine should be tested in
      concurrent chemoradiotherapy regimens. Significant toxicities seen in the initial
      trials have led to a number of trials modifying the regimen so that efficacy
      might be maintained without adverse effects. These modifications have included
      lowered gemcitabine doses and reduced radiation field sizes. The results of these
      newer studies suggest that this approach can be highly efficacious, with 1-year
      survival rates > 50% and response rates as high as 88%.

PMID- 14720351
TI  - Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer.
AB  - Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against
      non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%
      23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in
      NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy,
      respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%
      44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in
      NSCLC has a response rate of less than 25%. The major toxicity associated with
      pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate
      nutritional supplement. Additional studies with pemetrexed in combination with
      other agents are needed for the treatment of NSCLC patients.

PMID- 14720352
TI  - The evolving role of gemcitabine and pemetrexed (Alimta) in the management of
      patients with malignant mesothelioma.
AB  - Malignant mesothelioma is a refractory malignancy. Treatment for unresectable
      disease may provide a palliative benefit, but survival duration is impacted only
      minimally, if at all. Several newer agents, including difluorodeoxycytidine
      (gemcitabine) and pemetrexed disodium (LY231514, Alimta) appear to have activity
      against this neoplasm. Phase II data for combination regimens of gemcitabine and
      a platinum in mesothelioma patients have been encouraging. However, no phase III
      data are available to place these phase II results in true perspective. In phase
      I studies of a cisplatin/pemetrexed combination, objective responses occurred in
      several mesothelioma patients. This led to a phase II trial of pemetrexed alone
      in untreated mesothelioma patients and a randomized phase III trial of cisplatin
      alone versus pemetrexed/cisplatin. Phase II activity (15% partial response) was
      seen with single-agent pemetrexed. The phase III trial accrued over 450 patients.
      Primary analysis of the phase III data set has been completed and the results
      will be presented at the American Society of Clinical Oncology Meeting in May
      2002.

PMID- 14720354
TI  - Targets...targets...targets... Targeted therapies in lung cancer.

PMID- 14720353
TI  - Targeted therapy using novel agents in the treatment of non-small-cell lung
      cancer.
AB  - Patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis
      and high mortality. The therapeutic improvement caused by the new generation of
      cytotoxic agents seems to have reached a plateau. The main categories of targeted
      therapeutics applicable for NSCLC include receptor-targeted therapy, signal
      transduction or cell-cycle inhibition, angiogenesis inhibitors, gene therapy, and
      vaccines. Several major classes of agents directed at specific cellular
      mechanisms exist for the treatment of NSCLC. The anti-epidermal growth factor
      receptor (EGFR) group contains trastuzumab and IMC-C225, monoclonal antibodies
      against EGFRs that are overexpressed in many cancers. OSI-774 and ZD1839 are
      inhibitors of EGFR tyrosine kinase, a key enzyme of the signaling pathway.
      Farnesyl transferase inhibitors, such as SCH66336, and protein kinase C
      inhibitors, such as ISIS 3521, have also shown antitumor activity.
      Antiangiogenesis agents that have shown promise include TNP-470, recombinant
      endostatin, and angiostatin. Antibodies to vascular endothelial growth factor
      (VEGF) also seem to control tumor progression and may prolong survival. LY317615,
      an inhibitor of protein kinase Cb, augmented the tumor growth delay produced by
      cytotoxic drugs. All of these agents are in different phases of clinical testing
      and have shown encouraging activity as single agents or in combination with
      chemotherapy drugs. These new agents are more target specific, less toxic, easier
      to administer, and may lead to enhanced safety and survival for patients with
      advanced NSCLC.

PMID- 14720355
TI  - 37th Annual American Society of Clinical Oncology Meeting. San Francisco, CA. May
      12-15, 2000.

PMID- 14720356
TI  - Small molecule inhibitors of the epidermal growth factor receptor in patients
      with non-small-cell lung cancer: an update of clinical data from the 2001
      American Society of Clinical Oncology meeting.

PMID- 14720357
TI  - Inhibitors of vascular endothelial growth factor and its receptors in the
      treatment of lung cancer: an update of clinical data from the 2001 American
      Society of Clinical Oncology meeting.

PMID- 14720358
TI  - The curative potential of intraluminal bronchoscopic treatment for early-stage
      non-small-cell lung cancer.
AB  - Bronchoscopic treatment modalities such as lasers, electrocautery, cryotherapy,
      photodynamic therapy, and brachytherapy are potentially curative for patients
      with very-early-stage non-small-cell lung cancer (NSCLC) in the central airways.
      Previously, studies had primarily focused on the effectiveness of surgery,
      surgical bronchoplasty, and photodynamic therapy. The cure rate of intraluminal
      bronchoscopic treatment is strongly related to the patient's functional status
      and tumor stage. Intraluminal tumors are curable bronchoscopically when they are
      accessible to the fiberoptic bronchoscope, strictly intraluminal, and superficial
      with visible proximal and distal tumor margins. Early-stage cancer infiltrating
      deeper into the bronchial wall may already harbor metastases to the regional
      lymph nodes; hence, curative intraluminal treatment is not feasible. The use of
      new diagnostic tools (eg, high-resolution computed tomography, autofluorescence
      bronchoscopy, and endobronchial ultrasound) may improve staging to select the
      category of patients in whom intraluminal bronchoscopic therapy with curative
      intent is appropriate. An accurate intraluminal tumor staging will improve our
      ability to exploit the curative potential of many bronchoscopic techniques for
      complete tumor eradication in patients with very-early-stage intraluminal NSCLC
      in their central airways. The use of bronchoscopic treatment as a less morbid
      alternative than surgical resection will benefit patients most when tumor is
      detected at the earliest stage possible.

PMID- 14720360
TI  - Role of topoisomerase I inhibitors in small-cell lung cancer.
AB  - Lung cancer continues to be the leading cause of cancer-related death in the
      United States. Small-cell lung cancer constitutes 15%-20% of all cases of lung
      cancer. It is a chemosensitive disease with an overall response rate of 70%-90%
      in first-line treatment. However, the majority of patients relapse, and further
      treatment at that time is unlikely to achieve a durable response. Among the new
      drugs studied in this disease, topoisomerase I inhibitors are emerging as active
      agents with significant activity in both untreated and relapsed disease. This
      paper reviews the current status of irinotecan and topotecan in the treatment of
      small-cell lung cancer.

PMID- 14720361
TI  - Preliminary report on reduction of esophagitis by amifostine in patients with non
      small-cell lung cancer treated with chemoradiotherapy.
AB  - Esophagitis is a major toxicity of chemoradiotherapy for lung cancer. Twenty-four
      patients with non-small-cell lung cancer received induction chemotherapy
      (paclitaxel/carboplatin) followed by concurrent thoracic irradiation (RT) and
      weekly paclitaxel. Acute esophagitis was scored weekly. Since a high rate of
      grade 3 esophagitis was noted in the initial group of 12 patients, amifostine
      (AMI) 500 mg intravenously twice weekly was added to the regimen in the
      subsequent 12 patients. Esophagitis Index (EI) was calculated as an area under
      the curve reflecting esophagitis grade over time. Median number of AMI doses was
      12 per patient. AMI was well tolerated. Two patients were not evaluable for
      esophagitis. The incidence of grade 3 esophagitis was 18% in the initial 11
      patients versus 9% in the AMI-treated patients (P = not significant). Mean EI was
      numerically lower in the AMI-treated patients than in the initial group (5.1 vs.
      11.6, P = 0.14). The product of RT dose and length of esophagus in the RT field
      was larger in the AMI group (934 vs. 761, P = 0.035). Median survival time for
      all patients was 12.4 months. Esophagitis Index, a novel measure of the severity
      and duration of acute esophagitis, may be reduced in lung cancer patients
      receiving twice-weekly AMI with thoracic RT and paclitaxel. Twice weekly AMI did
      not eliminate grade 3 esophagitis; therefore, dose escalation of AMI is planned.
      The effect of AMI was not due to the shorter irradiated esophageal length. A
      phase III randomized trial is now open to assess AMI's effect on esophagitis.

PMID- 14720363
TI  - The role of video-assisted thoracic surgery for pulmonary metastasectomy.
AB  - Management of isolated metastatic deposits to the lungs and the role of surgical
      resection, specifically video-assisted thoracic surgery (VATS) techniques, have
      been controversial. The inability to perform a detailed bimanual palpation of the
      lung for occult lesions has been considered an inherent weakness in this
      approach. We have performed VATS resection for 205 patients with pulmonary
      metastatic disease and potentially curative VATS resec-tion for 119 patients.
      VATS resection was successfully performed for all VATS diagnostic and therapeutic
      patients, with no perioperative deaths. Longitudinal follow-up demonstrated a
      mean survival of 20 months in the diagnostic group and 32 months in the
      therapeutic group. In the VATS therapeutic group, 44 (37%) patients remain free
      of disease at a mean follow-up of 37 months. Of the 69 recurrences, 6% were
      local, 25% were regional, and 67% were distant. In this review, the present role
      of VATS pulmonary metastasectomy will be examined.

PMID- 14720364
TI  - Growth-stimulating pathways in lung cancer: implications for targets of therapy.
AB  - Growth-stimulating pathways activated independently of their normal tissue
      environment are critical to the carcinogenesis and progression of lung cancer.
      These pathways are comprised of extracellular growth factors; their specific
      receptors on the cellular membrane; signal transduction cascades in the cytosol;
      and target molecules, including cytoskeletal proteins, metabolic regulators, and
      transcription factors in the nucleus. Growth factors can be divided into two
      groups based on their receptors: G-protein-coupled receptors and receptor
      tyrosine kinases. Growth factors induce clonal expansion of lung cancer cells by
      autocrine and/or paracrine mechanisms. Signal transduction cascades form an
      extremely large and complicated network with cross-talk connections. Ras,
      phosphatidylinositol-3-OH kinase, and phospholipase C are three key regulators
      involved in the network. Recent progress in our understanding of the oncoproteins
      functioning in the pathways has led to the development of novel therapeutic
      agents. Some of the most exciting results have been obtained with inhibitors of
      receptor tyrosine kinases. Phase I studies of epidermal growth factor-receptor
      inhibitors demonstrate objective responses without severe toxicity as single
      agents in patients with non-small-cell lung cancer refractory to conventional
      chemotherapy. This new strategy might lead to breakthroughs in the treatment of
      lung cancer with distant metastases not curable by conventional chemotherapy
      alone.

PMID- 14720366
TI  - [Experimental studies on anti-tumor effects of BLC-modified tumor cell vaccine
      combined with cisplatin].
AB  - BACKGROUND & OBJECTIVE: Chemokines are small molecule proteins that are the main
      mediators of cell migration. Studies indicated that chemokines could induce
      antitumor immune response strongly and steadily. At present, there was not
      antitumor therapy about chemokine BLC combined with chemotherapy. This study was
      designed to explore the anti-tumor effects and mechanisms of BLC-modified tumor
      cell vaccine combined with cisplatin. METHODS: Firstly, we transfected pcDNA-BLC
      into murine tumor cell lines and established stable transfected tumor cell lines
      (Colon26 and LL/2) to express BLC. Null plasmid pcDNA3.1 (+) was also transfected
      into Colon 26 or LL/2 cells stably for comparison. We established mouse model
      with pcDNA-BLC stable transfected tumor cells (Tc), control mouse model with
      pcDNA3.1(+) stable transfected tumor cells (Pc), and mouse model with parental
      tumor cells (Nc). Then the 60 mice were inoculated subcutaneously (s.c.) in the
      right flanks with a total of 5x10(5) viable tumor cells (Tc to 20 mice, Pc to 20
      mice, and Nc to 20 mice, respectively; 6-8 week BALB/c female mouse in colon 26
      mouse model or 6-8 week C57BL/6 female mouse in LL/2 mouse model). The groups
      (Tc, Pc, and Nc) were randomly subdivided into Group A and Group B with 10 mice
      for each, resulting in Tc-A/Tc-B, Pc-A/Pc-B, and Nc-A/Nc-B, respectively. Group A
      (including Tc-A, Pc-A, and Nc-A) as chemotherapy group was injected (i.p.) with
      0.1 ml cisplatin at the concentration of 2 mg/kg once a week for two weeks; Group
      B (including Tc-B, Pc-B, and Nc-B) as control with 0.1 normal saline. We further
      observed anti-tumor activity including the tumor growth, mice survival rate, side
      effects as well as tumor morphological analysis. Apoptotic cells were also
      determined in tumor tissues. RESULTS: The combination therapy group Tc-A showed
      significant anticancer activities. The tumor growth was inhibited efficiently
      with 3/10 mice showing complete regression in LL/2 mouse model and 1/10 mice
      showing complete regression in Colon 26 mouse model. The combination therapy
      group Tc-A showed that the survival rate of mice was 100% in the two mouse
      models, compared with 68% in group Tc-B in C57BL/6 mouse model and 65% in group
      Tc-B in Colon 26 mouse model and those in other groups. In addition, the
      combination therapy group Tc-A induced tumor cell apoptosis significantly.
      CONCLUSIONS: The therapy of BLC-modified tumor cell vaccine combined with
      cisplatin had significant synergistic effect against tumor. It might develop a
      new approach for specific immunotherapy of tumors.

PMID- 14720367
TI  - [Expression and structure of BNIP3L in lung cancer].
AB  - BACKGROUND & OBJECTIVE: Bcl-2/E1B 19kDa interacting protein3-like (BNIP3L) gene
      is a tumor suppressor gene cloned from a human fetal liver cDNA library, which is
      located at 8p21, one of the high frequent regions of loss of heterozygosity (LOH)
      in lung carcinoma. BNIP3L protein can interact with antiapoptotic proteins, such
      as Bcl-2, Bcl-x(L), E1B19K, which promotes apoptosis. This study was designed to
      explore the correlation of alteration of expression and structure of BNIP3L gene
      with the progression of lung cancer. METHODS: The expression and structure of
      BNIP3L gene in 4 lung cancer cell strains and 30 tissues were determined by SP
      immunohistochemistry, immunoblot, semi-quantitative reverse transcription-PCR (RT
      PCR), PCR-single strain conformation polymorphism (PCR-SSCP). RESULTS: (1) In 4
      lung cancer cell strains, BNIP3L protein was not detected in A549, NCI-H460, NCI
      H446, except for NCI-H520, in which the protein expression level was slightly
      lower than that in immortal bronchial epithelial cell strain HBE4-E6/E7. BNIP3L
      protein was observed in 46.7% (14/30) lung cancer tissues, while 100% (12/12) in
      normal lung tissues. The difference was significant in statistics (P< 0.05). (2)
      BNIP3L mRNA was detected in 4 lung cancer cell strains; and there existed no
      obvious discrepancy of the amount between these cell strains and HBE4-E6/E7.
      Absence or decrease of BNIP3L mRNA was observed in 26.7%(8/30) of lung cancer
      tissues. The average quantity of BNIP3L mRNA was 0.404+/-0.070 in lung cancer
      tissues, while 0.575+/-0.065 in paired normal lung tissues. The difference was
      significant in statistics (P< 0.05). In all the cancerous cell strains and
      tissues with BNIP3L mRNA, the products of RT-PCR were as long as those from their
      control samples in size, including the entire coding region, and no variation of
      BNIP3L gene structure such as absence, rearrangement, aberrant splicing were
      detected.(3) No point mutation was detected in all 6 exons of BNIP3L gene in 4
      lung cancer cell strains and 30 tissues. CONCLUSION: BNIP3L protein expression
      was down-regulated in lung cancer, which might be involved in the occurrence
      and/or development of lung cancer. The down-regulation of BNIP3L protein
      expression in lung cancer was partly caused by the down-regulation of its
      transcription. The variation of gene structure may be not the reason of BNIP3L
      inactivity in lung cancer.

PMID- 14720368
TI  - [Relationship between protein tyrosine phosphorylation level and anoikis
      resistance of breast tumor cell lines].
AB  - BACKGROUND & OBJECTIVES: Normal epithelial or endothelial cells can undergo
      anoikis, a type of apoptosis, when they are detached from their extracellular
      matrices (ECM), while most tumor cells derived from epithelial or endothelial
      tissues lose this feature. Most of the studies indicate that anoikis resistance
      of tumor cells is closely related to abnormal signal transductioin. The aim of
      this research was to screen out the tumor cell lines that are anoikis resistant,
      then to investigate the relationship between the protein tyrosine phosphorylation
      of signaling molecules and anoikis resistance feature of tumor cells. METHODS:
      Anoikis resistance of breast tumor cell lines MCF-7, Bcap-37, and MDA-MB-231 was
      determined by DNA ladder assay, flow cytometry analysis, and soft agar assay upon
      suspending culture. A normal epithelial cell line MDCK (Madin-Darby canine
      kidney) was taken as a control. The inhibitory effect of genistein, a general
      protein tyrosine kinase inhibitor, on anoikis resistance of tumor cells was
      analyzed at the same time. The differences of total protein tyrosine
      phosphorylation levels between suspended and attached cultural conditions of
      three breast cancer cell lines were examined by Western blot analysis. RESULTS:
      All the three tumor cell lines were distinctly anoikis resistant. Further study
      showed that these features could be suppressed by genistein. The results of
      Western blot analysis showed that the general level of tyrosine phosphorylation
      in suspended MDCK cells was decreased compared with that in attached cells, while
      tyrosine phosphorylation level of some proteins increased (more than 3.5-6.5
      folds) aberrantly in suspended tumor cells. CONCLUSION: All the three breast
      tumor cells in this study are anoikis resistant respectively to some extent, and
      aberrant tyrosine phosphorylation of signaling proteins may play a role in the
      process of anoikis resistance of these tumor cells.

PMID- 14720369
TI  - [Migration and invasion of human hepatocellular carcinoma mediated by lung
      extracts].
AB  - BACKGROUND & OBJECTIVE: Invasion and metastasis are obstacles to successful
      treatment of hepatocellular carcinoma. Lung is the most common site of distant
      metastasis from hepatocellular carcinoma. In in vitro chemoinvasion assay that
      different tissue extracts from mice were used to induce human hepatocellular
      carcinoma cells with different metastatic potentials, lung extracts show the
      strongest inducing activity. This study was designed to investigate the mechanism
      of migration and invasion in human hepatocellular carcinoma with highly
      metastatic potential mediated by lung extracts from mice. METHODS: The changes of
      cytoskeleton were tested using F-actin polymerization assay and flow cytometry
      (FCM). Correlation between matrix metalloproteinas-9 and F-actin was analyzed by
      fluorescence double staining in human hepatocellular carcinoma MHCC97-H cells
      induced by lung extracts. RESULTS: When MHCC97-H cells were incubated with serum
      free medium or spleen extracts, the cells showed elongated or polygonal
      morphology. When MHCC97-H cells were incubated with lung extracts, the formation
      of lamelliopodia or filopodia became more and more obvious and distinct as time
      increasing. Results of FCM showed that 1.9-fold increase in intracellular F-actin
      within 30s after MHCC97-H cells were incubated with lung extracts. Confocal laser
      scan microscopy of MHCC97-H cells stimulated in suspension showed intense F-actin
      staining in the periphery of the cells and redistribution of F-actin towards a
      leading edge. MMP-9 and F-actin were mainly localized in the perinuclear pool
      when the cells were incubated with serum-free medium. After stimulation with lung
      extracts, MMP-9 and F-actin were localized at the front of extending pseudopodia
      of MHCC97-H cells. CONCLUSION: The mechanism that lung extracts promote migration
      and invasion of MHCC97-H may correlate with the pseudopodia formation and
      reorganization of MMP-9. Lung extracts may contribute to organ-specific
      metastasis of hepatocellular carcinoma.

PMID- 14720370
TI  - [Differential analysis of two-dimension gel electrophoresis profiles of human
      lung squamous carcinoma and tumor-adjacent tissue].
AB  - BACKGROUND & OBJECTIVE: Carcinogenesis of lung squamous carcinoma is a complex
      process involving multiple events and steps. Though some molecular pathogenesis
      studies on human lung cancer have been undertaken successfully in gene (DNA) and
      transcription (mRNA) levels, the carcinogenic mechanism is still unclear. At
      present, there is no special molecular marker for early-stage diagnosis and
      prognosis evaluation. The objective of this study was to establish two
      dimensional electrophoresis profiles with high resolution and reproducibility
      from human lung squamous carcinoma tissue and paired normal tumor-adjacent
      bronchial epithelial tissue, and to identify differential expression proteins.
      METHODS: The total proteins of human lung squamous carcinoma tissue and paired
      normal tumor-adjacent bronchial epithelial tissue were separated by immobilized
      pH gradient (IPG)-based two-dimensional gel electrophoresis (2-DE). The
      differential expression proteins were analyzed using image analysis software,
      then identified using mass spectrometry and database searching. RESULTS: (1) For
      tumor tissues, the average protein spots of 3 gels were 1349+/-67; and 1235+/-48
      spots were matched with the average matching rate of 91.5%. For control, the
      average protein spots of 3 gels were 1297+/-73; and 1183+/-56 spots were matched
      with the average matching rate of 91.2%. The average position deviation of
      matched spots was 0.873+/-0.125 mm in IEF direction, and 1.025+/-0.213 mm in SDS
      PAGE direction. (2) A total of 1069+/-45 spots were matched between the
      electrophoretic maps of 15 human lung squamous carcinoma tissue and paired normal
      tumor-adjacent bronchial epithelial tissue. Forty differential proteins were
      identified by peptide mass fingerprint(PMF), some proteins were the products of
      oncogenes, and the others involve in the regulation of cell cycle and signal
      transduction. CONCLUSION: In this study, the well-resolved, reproducible 2-DE
      patterns of human lung squamous carcinoma and adjacent normal bronchial
      epithelial tissues were established and certain differential proteins were
      characterized. These data will be helpful for screening the biomarker to further
      study on human lung squamous carcinoma.

PMID- 14720371
TI  - [Relationship between gastric cancer and gene amplification of p14 and mdm2].
AB  - BACKGROUND & OBJECTIVE: Some genes are related to the occurrence of tumor. p53 is
      one of these kinds of gene. Mdm2 and p14 can modulate the function of p53.
      However, the reports about the function of mdm2 and p14 in gastric tumor are
      rare. The aim of this study was to observe the change of oncogene mdm2 and
      suppressor cancer gene p14 in gastric cancer cell and to investigate the
      relationship of mdm2, p14 with gastric cancer. METHODS: A total of 55 gastric
      mucosal biopsy specimens were enrolled, including 10 of normal gastric mucosa and
      45 gastric tumor, which were proved pathologically as adenoma, including 15
      poorly, moderately, and well differentiated specimens, respectively. The mRNA
      expression of mdm2 and p14 in gastric cancer were identified by reverse
      transcription polymerase chain reaction (RT-PCR), and the relationship of mdm2,
      p14 with gastric cancer was analyzed. RESULTS: (1) There was significant
      difference of the expression positive ratio of mdm2 mRNA between gastric tumor
      and normal gastric tissues (73.3% vs. 40%) (P< 0.05) [93.3% for the well
      differentiated specimens, 80.0% for the moderately differentiated specimens, and
      46.6% for the poorly differentiated specimens]. There was significant difference
      between any two groups of the three specimens (P< 0.05). (2) There was no
      significant difference of the expression positive ratio of p14 mRNA between
      gastric tumor and normal gastric tissues (60.0% vs. 50.0%) (P >0.05) [60.0% for
      the well differentiated specimens, 66.6% for the moderately differentiated
      specimens, and 53.5% for the poorly differentiated specimens]. There was no
      significant difference between any two groups of the three specimens (P >0.05).
      CONCLUSION: The mRNA expression of mdm2 is closely correlated with the
      progression of gastric cancer. The relationship between p14 and gastric tumor has
      not been tested in this study and further study will be needed.

PMID- 14720372
TI  - [Expression of survivin and caspase-3 in non-Hodgkin's lymphoma and their
      clinical significance].
AB  - BACKGROUND & OBJECTIVE: Survivin, a member of the inhibitor of apoptosis protein
      (IAP) family, can directly inhibit caspase-3 and caspase-7 activity and plays an
      important role in oncogenesis. This study was designed to investigate the
      expression of survivin and caspases-3 in non-Hodgkin's lymphoma (NHL) with
      different aggressiveness and their clinical significance. METHODS: The expression
      of survivin and caspase-3 in 54 cases of NHL were determined with
      immunohistochemistry of EnVision. RESULTS: The expression rates of survivin and
      caspase-3 were 51.9% (28/54) and 83.3% (45/54), respectively. The expression of
      survivin in NHL patients with low grade malignancy (19%, 4/21) was lower than
      that of NHL patients with intermediate-high grade malignancy; the difference was
      statistically significant. The expression of caspase-3 showed the same tendency.
      Co-expression rate of survivin and caspase-3 was 46.3% (25/54). CONCLUSION: The
      expression of survivin is upregulated in NHL.

PMID- 14720373
TI  - [In vitro cytotoxicity of Helicobacter pylori on hepatocarcinoma HepG2 cells].
AB  - BACKGROUND & OBJECTIVE: Helicobacter pylori (HP) is the important pathogen of
      chronic gastritis and peptic ulcer. HP infection is closely associated with
      extragastrointestinal disease of human and animals. This study was designed to
      investigate the effect of HP on hepatocarcinoma HepG2 cells. METHODS: HepG2 cells
      was cocultured with cagA (+) HP and cagA(-) HP at different concentrations. Then
      the cell morphology, DNA fragments electrophoresis, transmission electron
      microscopy, MTT method, and enzyme assays were used to observe the effect of HP
      on the morphology, growth rate, and enzyme change of HepG2 cells. RESULTS: (1)
      With the increasing concentrations of cagA (+) HP and prolongation of culture
      time, the morphology of HepG2 cells was changed from spindle shape to round; the
      ability of HepG2 cells adhering to wall were decreased; the ability of HepG2
      cells in suspension were increased; and debris emitted around the cells; (2) With
      the increasing concentrations of cagA (+) HP, DNA ladder occurred; (3) With the
      increasing concentrations of cagA (+) HP and prolongation of culture time, the
      nuclei of HepG2 cells showed chromatin pyknosis, and clustered on the inner
      border of karyotheca, condensed cytoplasm with many vacuoles; (4) The MTT values
      of HepG2 cells were decreased with the increasing concentration of cagA(+) HP (P<
      0.01); (5)The values of alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) in coculture supernatants of cagA (+) Hp and HepG2 were increased (P<
      0.01); (6) No influence of cagA (-) Hp on HepG2 was found. CONCLUSIONS: cagA (+)
      Hp has in vitro cytotoxicity on HepG2 cells, and the cytotoxicity is positively
      related to the concentration and culture time of cagA(+) HP.

PMID- 14720374
TI  - [Construction and screening of a ribozyme targeting telomerase RNA and effects of
      telomerase ribozyme on proliferation and apoptosis of CNE-2Z cells].
AB  - BACKGROUND & OBJECTIVE: It was proved that telomerase is an important determinant
      in tumor progression and cell immortalization. Ribozyme is a special kind of
      trans-acting RNA with endonuclease activity and sequence-specific catalytic RNA
      molecules, which can cleave target RNA. It was reported that telomerase activity
      is present in human poorly-differentiated nasopharyngeal carcinoma (NPC) CNE-2Z
      cells. This study was designed to construct eukaryotic expression plasmids
      containing telomerase ribozyme (teloRZ)gene targeting the template region of
      human telomerase RNA (hTR) and then to transfect the plasmids into CNE-2Z cells
      by electroporation to investigate the effect of teloRZ on proliferation and
      apoptosis of those transfected CNE-2Z cells. METHODS: Hammer ribozyme gene teloRZ
      directed against telomerase RNA templet was designed and synthesized to serve as
      a telomerase inhibitor. Three different eukaryotic expression plasmids carried
      with the green fluorescent protein (GFP) reporter gene and puromycin-resistance
      gene and containing teloRZ gene were constructed. They were referred to as
      pGFPuro-teloRZ2.1, pGFPuro-teloRZ7.1, and pGFPuro-teloRZ7.7 and differed in the
      relative orientation of the genes for telomerase-ribozyme and puromycin
      resistance. The CNE-2Z cells were transfected with three expression plasmids and
      control plasmid pPAT-GFP by electroporation. The expression of GFP was detected
      by fluorescent microscope; cellular proliferation index (PI) and apoptosis were
      investigated by flow cytometry analysis and fluorescence staining. RESULTS: PI of
      CNE-2ZGTR7.1 cells transfected by plasmid pGFPuro-teloRZ7.1 (25.100%+/-0.141%)was
      significantly lower than those of CNE-2Z cells untransfected by any plasmid
      (53.663%+/-16.981%),CNE-2ZG cells transfected by control plasmid pPAT-GFP
      (61.575%+/-5.166%),CNE-2ZGTR2.1 cells transfected by plasmid pGFPuro-teloRZ2.1
      (61.500%+/-20.082%), and CNE-2ZGTR7.7 cells transfected by plasmid pGFPuro
      teloRZ7.7 (59.400%+/-13.933%) (P< 0.01). GFP was detected in CNE-2ZG cells,CNE
      2ZGTR7.1 cells, and CNE-2ZGTR7.7 cells;while there was no GFP expression in CNE
      2Z cells and CNE-2ZGTR2.1 cells. The plasmid pGFPuro-teloRZ7.1 was selected from
      3 plasmids for further experiments. Apoptosis could be observed in CNE-2ZGTR7.1
      cells after 12 generations. There was no apoptosis occurring in CNE-2Z and CNE
      2ZG cells. CONCLUSION: The teloRZ7.1 gene was electroporated successfully into
      CNE-2Z cells. TeloRZ7.1 can inhibit the proliferation and induce apoptosis of CNE
      2Z cells. These findings suggest the potential application of ribozyme teloRZ7.1
      as telomerase inhibitor.

PMID- 14720375
TI  - [Modified radical operation for early breast cancer for preserving nipple-areolar
      complex and breast reconstruction using transverse rectus abdominis myocutaneous
      (TRAM) flap].
AB  - BACKGROUND & OBJECTIVE: Modified radical mastectomy (MRM) operation has become an
      important surgical therapy for early stage breast cancer, but how to reconstruct
      breast and preserve nipple-areolar complex (NAC) is controversial. In this study,
      we applied a modified radical mastectomy for early stage breast cancer for
      preserving NAC and breast reconstruction using transverse rectus abdominis
      myocutaneous (TRAM) flap. METHODS: During operation we performed the subcutaneous
      glandular excision and axillary dissection, and reconstructed the breast using
      TRAM flap in 10 patients with early stage breast cancer; meanwhile, maximam
      extent of breast skin and NAC were preserved. RESULTS: The appearance of the
      reconstructed breast was better preserved after operation. No local recurrence
      and distant metastasis occurred in the patients during the follow up time (range
      24-48 months). No skin flap necrosis, atrophy, and scleroses surround the NAC
      were observed; and no abdominal wall hernia occurred at the donor site. The
      nipple sensation was recovered half a year after surgery. CONCLUSION: Modified
      radical operation for preserving NAC and breast reconstruction using TRAM flap
      may be a better way for breast cancer patients in early stage who request well
      preserving of breast. More samples are needed for proving the effects of this
      operation.

PMID- 14720376
TI  - [Modification for primary tongue reconstruction with free forearm flap after
      radical operation of tongue carcinoma].
AB  - BACKGROUND & OBJECTIVE: Radical operation of tongue carcinoma causes hemi-tongue
      defective, which seriously affected the quality of life in these patients. The
      primary tongue reconstruction guaranteed the healing of the surgical incision at
      early stage. This may help to recover swallowing and speaking of the patients.
      However, the vascular crisis happened in the free flap proved to be an obstacle
      to the extensive application in the tongue reconstruction. This paper illustrated
      some modifications in the application of the free forearm flap, which may ensure
      the success in operation. METHODS: Some methods like skin flap design,
      preparation and vascular anastomosis were modified in the application among the
      32 tongue carcinoma patients. RESULTS: The surgical incisions of the oral cavity
      and neck healed up, with no salivary fistula, chylorrhea, submandibular fistula,
      infection and other complications. After the operations, 6 flaps developed
      vascular crisis, and 5 flaps were successfully salvaged, meanwhile, one case
      failed, which resulted in the flap abandonment. The total successful
      transplantation rate reached 96.9%. The reconstructed tongue recovered, and the
      speaking as well as swallowing functions re-obtained. CONCLUSION: The modified
      methods of tongue reconstruction with free forearm flap improve the clinical
      effects of reconstructed tongue.

PMID- 14720377
TI  - [Expression of cyclin D1 in brain gliomas and its significance].
AB  - BACKGROUND & OBJECTIVE: Overexpression of cyclin D1 was shown in many tumors. The
      excessive expression of cyclin D1 is an important cause of many tumors. But there
      are still some controversies of whether the overexpression of cyclin D1 exists in
      brain gliomas. This study was to determine the expression level of cyclin D1 in
      glioma tissues of human brain, and to analyze the relationship of cyclin D1 with
      the malignancy and prognosis of gliomas. METHODS: The expression levels of cyclin
      D1 in 84 specimens were determined by SP immunohistochemical assay. The
      correlation of expression intensity of cyclin D1, positive cell ratio of glioma
      tissues with the tumors malignancy, and the prognosis of the patients was
      analyzed. RESULTS: (1) The average percentages of cyclin D1 positive cells were
      (9.82+/-9.75)% and (27.45+/-21.03)% in the low grade gliomas and the high grade
      gliomas, respectively. There was significant difference between two groups (P<
      0.01). (2) The cyclin D1 positive ratios were 31.25% (10/32) and 61.53% (32/52)
      in the low grade gliomas and the high grade gliomas, respectively. There was
      significant difference between two groups (P< 0.01). (3) The cyclin D1 positive
      ratios were 76.19% (16/21) and 24.00% (6/25) in recurrence group and non
      recurrence group,respectively. There was significant difference between two
      groups (P< 0.01). (4) The cyclin D1 positive ratios were 66.67% (14/21) and
      32.00%(8/25) in dead group and survival group, respectively. There was
      significant difference between two groups (P< 0.05). In dead group, the cyclin D1
      positive ratios were 86.66%(13/15) and 16.66%(1/6) in the high grade gliomas and
      the low grade gliomas, respectively. There was significant difference between two
      groups (P< 0.05). CONCLUSIONS: (1) The expression of cyclin D1 increased with the
      increased grade of glioma. (2) The higher cyclin D1 expressed, the worse
      prognosis the patients had. (3) The expression of cyclin D1 can act as a
      biological marker in evaluating malignancy of gliomas and prognosis of patients.

PMID- 14720378
TI  - [Detection of GGT-II by dot-ELISA with monoclonal antibody in the diagnosis of
      hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Hepatoma-specific gamma- glutamyltransferase isoenzyme
      II(GGT-II) is considered as the best hepatoma marker except alpha-fetoprotein
      (AFP), but there is no simple and easy method to determine it now. The purpose of
      this study was to explore the value of detection of GGT-II by dot-ELISA with
      monoclonal antibody in the diagnosis of hepatocellular carcinoma (HCC). METHODS:
      GGT-II was purified and then BALB/c mouse was immunized. The monoclonal antibody
      against GGT-II was raised by the hybridoma technique. Serum GGT-II was detected
      in 123 cases with hepatocellular carcinoma and 164 cases with various benign
      liver diseases using both dot-ELISA and electrophoresis simultaneously. RESULTS:
      The positive rate of serum GGT-II in HCC by dot-ELISA was 71.5%, which was not
      significantly different from that by electrophoresis (76.4%). However, the false
      positive rates of GGT-II by dot-ELISA in liver cirrhosis (23.7%) and chronic
      hepatitis (27.1%) were significantly higher than those by electrophoresis (10.0%
      and 8.4% for liver cirrhosis and chronic hepatitis, respectively). CONCLUSION:
      Detection of GGT-II by dot-ELISA with monoclonal antibody is helpful for the
      diagnosis of HCC, but its diagnostic specificity deserves to be improved.

PMID- 14720379
TI  - [Detection of mutation and protein expression of PTEN gene in endometrial
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: PTEN (phosphatase and tensin homolog deleted on
      chromosome ten), a novel tumor suppressor gene identified recently, is called the
      house-keeping gene of endometrium. However, little is known about its precise
      role in genesis and development of endometrial carcinoma. In the present study,
      the mutation and protein expression of PTEN gene were investigated to seek the
      clinical significance. METHODS: Fifty-two endometrial carcinoma samples and 10
      normal endometrial tissues were collected. The mutations of exon 5 and exon 8 of
      PTEN gene were examined by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and DNA sequencing analysis. The expression of PTEN
      protein was evaluated by immunohistochemistry method. The results associated with
      clinical pathological features were analyzed. RESULTS: In endometrial carcinomas,
      the rates of mutation and protein expression deletion of PTEN were 25% and 60%,
      respectively, which were significantly higher than that of normal endometrium
      (0%) (P< 0.05). The samples at pathological G(1) and G(2) and depth of myometrial
      invasion less than 1/2 demonstrated higher mutation rate than that of G3 and
      depth of myometrial invasion more than or equal to 1/2 (P< 0.05). In contrast,
      the rate of protein expression deletion of G(1) and G(2) was significantly lower
      than that of G3 (P< 0.05). Both mutation and protein expression deletion showed
      statistical differences between endometrioid adenocarcinoma and other types of
      endometrial carcinomas (P< 0.05), but no significant difference was found at
      different surgical-pathological stage (P >0.05). CONCLUSION: Mutation and
      positive protein expression of PTEN occurred more frequently in the endometrial
      carcinoma cases with low pathological stages.

PMID- 14720380
TI  - [Expression of p21(WAF1) and its relationship with p53 and PCNA protein in
      epithelial ovarian cancer].
AB  - BACKGROUND & OBJECTIVE: Recent researches manifested that down-regulation of
      p21(WAF1) had relationship with carcinogenesis and development in various tumors,
      but its association with epithelial ovarian cancer (EOC) was not clear. This
      study was designed to investigate the role of p21(WAF1) in the tumorigenesis and
      development of EOC and its relationship with p53 and proliferating cell nuclear
      antigen (PCNA) protein. METHODS: Fifty-five EOC tissues, 32 benign ovarian tumor
      tissues, and 30 normal ovarian tissues were collected. Reverse transcription
      polymerase chain reaction (RT-PCR) was applied to determine the p21(WAF1)mRNA
      expression. Immunohistochemistry was applied to examine the protein expression of
      p21(WAF1), p53, and PCNA. The relationship between the expression of these
      markers and the clinicopathological characteristics, prognosis of the patients
      was analyzed. RESULTS: The positive rates of p21(WAF1)mRNA in EOC, benign ovarian
      tumor, and normal ovary were 40%, 56.25%, and 73.33%, respectively (P=0.012). The
      positive rates of p21(WAF1) protein were 36.36%, 56.25%, and 80%, respectively
      (P=0.001). The positive expression rates of p21(WAF1)mRNA and its protein in EOC
      were lower than those of the other two groups, while the positive expression
      rates of p53 and PCNA protein in EOC were higher than those of the other two
      groups (P< 0.05). Expression of p21(WAF1)mRNA had positive relation to its
      protein, negative relation to PCNA protein, no relation to p53 protein, while
      expression of p21(WAF1) protein had negative relation to p53 and PCNA protein in
      EOC. Low-expression of p21(WAF1) protein was associated with advanced FIGO stage
      (P=0.032), but not with age, histological type, pathological grade, and remnant
      tumor (P >0.05). There was no relationship between p21(WAF1)mRNA and former
      parameters (P >0.05). Univariate analysis showed that the patients with low
      expression of p21(WAF1)mRNA and p21(WAF1) protein had poor prognosis (P< 0.05).
      CONCLUSION: p21(WAF1) is down-regulated in EOC. p21(WAF1) might be able to be
      used as a marker to predict the prognosis of patients with EOC.

PMID- 14720381
TI  - [Significance of concentration of serum soluble vascular cell adhesion molecule-1
      in epithelial ovarian carcinoma].
AB  - BACKGROUND & OBJECTIVE: It was reported that vascular cell adhesion molecule-1
      (VCAM-1) was highly expressed in ovarian carcinoma samples. The latest research
      showed that the concentration of serum soluble VCAM-1 (sVCAM-1) was increased in
      the patients with various tumors. The aim of this study was to investigate the
      biological effects of sVCAM-1 on epithelial ovarian carcinoma. METHODS: The
      concentration of serum sVCAM-1 was assayed in 130 normal cases, 50 benign ovarian
      tumors, and 67 epithelial ovarian carcinoma cases using enzyme-linked
      immunoadsorbent assay(ELISA). RESULTS: The serum sVCAM-1 level in epithelial
      ovarian carcinoma[(897+/-54) g/L,83.6%] was higher than those in benign ovarian
      tumor [(435+/-43) g/L, 8.0%] and normal cases [(420+/-40) microg/L,6.2%] (P<
      0.01), while the former dropped post-operation [(532+/-46) microg/L,37.3%]. The
      serum sVCAM-1 levels in stage II-IV [(899+/-71) microg/L,93.3%], grade III
      [(982+/-66) microg/L,94.8%], and the cases combined with lymphatic metastasis
      [(895+/-58) microg/L,95.1%] were higher than those in stage I[(571+/-49)
      microg/L,63.6%], grade I [(641+/-51)microg/L,69.2%], grade II[(768+/
      47)microg/L,66.7%], and the cases without lymphatic metastasis[(728+/-47)
      microg/L,65.4%](P< 0.05, P< 0.01, and P< 0.01, respectively); while no
      correlation was found between serum sVCAM-1 levels and histological types (P
      >0.5). No correlation was found between concentration of sVCAM-1 and prognosis by
      multiple factor analysis. CONCLUSION: Dynamically monitoring the concentration of
      serum sVCAM-1 will hopefully become an index for early diagnosis and supervising
      the recurrence of epithelial ovarian carcinoma.

PMID- 14720382
TI  - [Clinical significance of detecting VEGF, CD44v6, MMP-2, and MMP-9 in malignant
      ascites].
AB  - BACKGROUND & OBJECTIVE: Cytological examination, despite of its high specificity,
      has been found to have a low sensitivity in the diagnosis of malignant ascites
      due to the high percentage of false negative results. So it is indispensable to
      seek appropriate cancerous markers in ascites. The aim of this study was to
      determine vascular endothelial growth factor (VEGF), CD44v6 levels and matrix
      metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) activities in
      ascites so as to provide scientific basis for clinical diagnosis and treatment of
      malignant ascites. METHODS: A total of 67 samples were collected, including
      cirrhotic ascites (36), tuberculosis ascites (8), and malignant ascites (23).
      VEGF and CD44v6 levels were determined using enzyme-linked immunosorbent assay
      (ELASA). MMP-2 and MMP-9 activities were determined by gelatin zymography.
      RESULTS: VEGF and CD44v6 levels in malignant ascites were 640.74+/-264.81 ng/L
      and 89.22+/-38.20 microg/L, respectively, which were significantly higher than
      those in cirrhotic ascites (67.05+/-51.91 ng/L, 44.79+/-18.02 microg/L) and
      tuberculosis ascites (88.25+/-24.12 ng/L, 50.25+/-12.57 microg/L) (P< 0.01,
      respectively). The activities of MMP-2 and MMP-9 could not be detected in
      cirrhotic ascites and tuberculosis ascites but could be detected in 20 and 18 out
      of 23 malignant ascites respectively. CONCLUSION: VEGF, CD44v6 levels increase
      significantly and MMP-2, MMP-9 activities are obvious in cancerous ascites. The
      detection of VEGF, CD44v6 levels and MMP-2, MMP-9 activities are useful in
      differential diagnosis of benign and malignant ascites.

PMID- 14720383
TI  - [Expression of p73 and PTEN in laryngeal squamous cell carcinoma and their
      clinical significance].
AB  - BACKGROUND & OBJECTIVE: There are few ideal predictors used to evaluate the
      prognosis of laryngeal squamous cell carcinoma (LSCC). This study was designed to
      investigate the expression of p73 and PTEN (phosphates and tension homolog
      deleted on chromosome ten) and their association with clinical, histologic
      characteristics and prognosis in LSCC. METHODS: p73 protein and PTEN protein were
      examined by using immunochistochemical SABC staining method in 65 cases of LSCC
      and in 23 cases of para-tumor tissues. RESULTS: p73 protein and PTEN protein in
      LSCC showed positive expression of about 58.5% (38/65) and 49.2% (32/65),
      compared to para-tumor tissues of about 17.4% (4/23) and 95.7% (22/23) with
      statistical significance (P< 0.05). p73 protein positive expression showed
      stronger in stage III-IV of LSCC than that in stage I-II (P< 0.05); it more often
      appeared in recurrent cases than in primary cases (P< 0.05). And p73 protein
      positive expression with distant metastasis was stronger than that in LSCC
      without distant metastasis (P< 0.05). PTEN protein positive expression was
      stronger in stage I-II of LSCC than that in stage III-IV (P< 0.05); PTEN protein
      positive expression appears less frequently in poor differentiation of LSCC,
      compared to well/moderate differentiation (P< 0.05); PTEN positive expression in
      cases with cervical lymph node metastasis and distant metastasis was lower than
      that in those without metastasis (P< 0.05). PTEN expression showed significantly
      stronger in the patients whose survival time over 5 years (66.7%) than in the
      patients whose survival time was less than 5 years (27.3%) (P< 0.05). CONCLUSION:
      PTEN positive expression may be useful for predicting the prognosis of LSCC.

PMID- 14720384
TI  - [Study progress of p73 gene in digestive system carcinoma].
AB  - p73 gene is a new member of the tumor suppressor gene p53 family. They are
      similar in the structure and function of the coding protein, but they also have
      notable distinctions in other aspects. Many studies have shown that the abnormal
      p73 gene is associated with neuroblastoma, malignant melanoma, prostatic
      carcinoma, and lung cancer, et al. Recently, many studies have demonstrated that
      p73 gene may involve the occurrence and development of a portion of the digestive
      system carcinoma. This review summarized the present conditions of the p73 gene
      and its correlation with the occurrence, development, prognosis, and expression
      in the digestive system carcinoma. We suggested that the further study about the
      p73 gene may be helpful to recognize the nature of the carcinoma and bring wish
      to overcome it finally.

PMID- 14720385
TI  - [Abnormalities of molecular biology in premalignant lung lesions].
AB  - In recent twenty years, the incidence of lung cancer has increased quickly in our
      country. Till now, the morbidity and mortality of lung cancer have occupied the
      top of the cancers. Early diagnosis is the most important key to increase the
      five-year survival rate. This review is attempted to summarize the early
      hereditary events during the development of lung cancer, mainly including the
      mutation of p53 gene, the abnormal methylation of the promoter area of p16 gene,
      the loss of heterozygosity of 3p, 8p, 9p, 5q, etc. The purpose is to seek the
      biological markers during the development of lung cancer to provide theoretical
      basis for treatment of lung cancer.

PMID- 14720386
TI  - [Detection of chromosomal aberrations in nasopharyngeal carcinoma by rapid primed
      in situ labeling].
AB  - BACKGROUND & OBJECTIVE: The chromosomal aberration is common in nasopharyngeal
      carcinoma (NPC). The currently-used methods for detecting chromosomal
      abnormalities are complicated and of limited clinical value. The purpose of the
      present study was to explore the feasibility of detecting chromosomal
      abnormalities in NPC by rapid primed in situ labeling (RPRINS). METHODS: Using
      RPRINS technique with specific oligonucleotide primers of chromosome 3 and 7, the
      abnormalities of chromosome 3 and 7 in the frozen section tissues of 15 cases of
      NPC and 5 cases of normal nasopharyngeal mucosa (NNM) were detected. Loss of
      chromosome was defined when the percentage of cells with labeling signals </=1
      was >/=65%, and the increase in chromosomal copy number was defined when the
      percentage of cells with labeling signals >/=3 was >/=6.5%. RESULTS: In 15 cases
      of NPC tissues, the chromosome 3 had a labeling rate of 88.6% and increasing copy
      numbers in ten cases (66.7%), and the chromosome 7 had a labeling rate of 87.4%
      and loss of chromosome in five cases (33.3%). Four cases coexisted with
      increasing chromosome 3 copy numbers and loss of chromosome 7. In contrast, the
      labeling rates of chromosome 3 and 7 in NNM were 92.0% and 91.8%, respectively,
      and the percentage of diploid cells were 43.2% and 43.6%, respectively, with
      absence of triploid. There was a significant difference in the percentage of
      diploid cells between NPC and NNM (P< 0.05). CONCLUSION: The technique of rapid
      PRINS could be used to detect chromosomes in frozen section tissues, and the
      chromosomal abnormalities would be helpful in diagnosis of NPC.

PMID- 14720387
TI  - [Endoscopic management of bilateral ureteral obstruction after radiotherapy].
AB  - BACKGROUND & OBJECTIVE: It is difficult to stent the obstructed ureters
      cystoscopically in patients with renal failure caused by radiotherapy for
      abdominal or pelvic tumors. Commonly draining the kidney with nephrostomy is the
      only method for the patients. However, external nephrostomy impacts on life
      quality of the patients. We reported our experience in stenting the obstructed
      ureters using minimally invasive percutaneous nephrostomy combined with
      ureteroscopy, and investigated viability of endoscopic treatment for bilateral
      ureteral strictures following radiotherapy. METHODS: Indwelling double pigtail
      stents in ureter by minimally invasive percutaneous nephrostomy combined with
      ureteroscopy was carried out in 19 patients with bilateral ureteral strictures
      following radiotherapy. The clinical outcomes including ureteral drainage and
      renal function were reviewed. RESULTS: Bilateral retrograde placement of double
      pigtail stent was performed in 2 cases. Indwelling different size double pigtail
      stents in unilateral ureters were carried out in 17 cases. The patients were
      followed-up for 1-24 months. Renal function was improved excellently in 17 cases,
      with serum creatinine level of 45 micromol/L to 113 micromol/L. Two patients had
      poor renal function improvement after ureteral stenting and were converted to
      percutaneous nephrostomy for draining the kidney. CONCLUSION: Indwelling
      different size double pigtail stents simultaneously in unilateral ureter by
      minimally invasive percutaneous nephrostomy is safe, simple, and effective in
      treating bilateral ureteral obstruction following radiotherapy.

PMID- 14720388
TI  - Emerging infectious diseases in Mongolia.
AB  - Since 1990, Mongolia's health system has been in transition. Impressive gains
      have been accomplished through a national immunization program, which was
      instituted in 1991. Nevertheless, the country continues to confront four major
      chronic infections: hepatitis B and C, brucellosis, tuberculosis, and sexually
      transmitted diseases (STDs). As of 2001, only two cases of HIV infections had
      been detected in Mongolia, but concern grows that the rate will increase along
      with the rising rates of STDs and increase in tourism. Other infectious diseases
      of importance in Mongolia include echinococcosis, plague, tularemia, anthrax,
      foot-and-mouth, and rabies.

PMID- 14720389
TI  - Raccoon roundworm eggs near homes and risk for larva migrans disease, California
      communities.
AB  - The raccoon roundworm, Baylisascaris procyonis, is increasingly recognized as a
      cause of serious or fatal larva migrans disease in humans and animals. We
      assessed the potential for infection in three northern California communities by
      determining the density and distribution of raccoon latrines, where transmission
      primarily occurs, and the prevalence of eggs at private residences. We collected
      fecal samples from 215 latrines and found that 44%-53% of the latrines contained
      B. procyonis eggs and that 16%-32% contained infective eggs. Among the properties
      surveyed, 28%-49% harbored at least one latrine that was positive for B.
      procyonis eggs. The latrine densities in these communities were higher than any
      previously reported. The presence of B. procyonis eggs in raccoon latrines was
      common, widespread, and closely associated with human habitation. Where raccoon
      densities are high, education of the public and removal of raccoons may be
      necessary.

PMID- 14720390
TI  - Global distribution of rubella virus genotypes.
AB  - Phylogenetic analysis of a collection of 103 E1 gene sequences from rubella
      viruses isolated from 17 countries from 1961 to 2000 confirmed the existence of
      at least two genotypes. Rubella genotype I (RGI) isolates, predominant in Europe,
      Japan, and the Western Hemisphere, segregated into discrete subgenotypes;
      international subgenotypes present in the 1960s and 1970s were replaced by
      geographically restricted subgenotypes after approximately 1980. Recently, active
      subgenotypes include one in the United States and Latin America, one in China,
      and a third that apparently originated in Asia and spread to Europe and North
      America, starting in 1997, indicating the recent emergence of an international
      subgenotype. A virus that potentially arose as a recombinant between two RGI
      subgenotypes was discovered. Rubella genotype II (RGII) showed greater genetic
      diversity than did RGI and may actually consist of multiple genotypes. RGII
      viruses were limited to Asia and Europe; RGI viruses were also present in most of
      the countries where RGII viruses were isolated.

PMID- 14720391
TI  - Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo.
AB  - We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic
      fever in an area of confirmed Marburg virus transmission in the Democratic
      Republic of the Congo. Questionnaires were administered and serum samples tested
      for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen
      (2%) of 912 participants in a general village cross-sectional antibody survey
      were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15
      were men who worked in the local gold mines. Working as a miner (odds ratio [OR]
      13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4,
      95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103
      participants in a targeted antibody survey of healthcare workers were antibody
      negative. Primary transmission of Marburg virus to humans likely occurred via
      exposure to a still unidentified reservoir in the local mines. Secondary
      transmission appears to be less common with Marburg virus than with Ebola virus,
      the other known filovirus.

PMID- 14720392
TI  - Intensity of rainfall and severity of melioidosis, Australia.
AB  - In a 12-year prospective study of 318 culture-confirmed cases of melioidosis from
      the Top End of the Northern Territory of Australia, rainfall data for individual
      patient locations were correlated with patient risk factors, clinical parameters,
      and outcomes. Median rainfall in the 14 days before admission was highest (211
      mm) for those dying with melioidosis, in comparison to 110 mm for those surviving
      (p=0.0002). Median 14-day rainfall was also significantly higher for those with
      pneumonia. On univariate analysis, a prior 14-day rainfall of 125 mm was
      significantly correlated with pneumonia (odds ratio [OR] 1.70 [confidence
      interval [CI] 1.09 to 2.65]), bacteremia (OR 1.93 [CI 1.24 to 3.02]), septic
      shock (OR 1.94 [CI 1.14 to 3.29]), and death (OR 2.50 [CI 1.36 to 4.57]). On
      multivariate analysis, rainfall in the 14 days before admission was an
      independent risk factor for pneumonia (p=0.023), bacteremic pneumonia (p=0.001),
      septic shock (p=0.005), and death (p<0.0001). Heavy monsoonal rains and winds may
      cause a shift towards inhalation of Burkholderia pseudomallei.

PMID- 14720393
TI  - Comparative molecular and microbiologic diagnosis of bacterial endocarditis.
AB  - Sequencing of 16S rDNA, and of sodAint and rpoBint in some cases, was applied to
      DNA from heart valves of 46 patients (36 with definite and 10 with possible
      endocarditis). Sequence-based identifications were compared with those obtained
      with conventional methods. Among the 36 definite cases, 30 had positive blood
      cultures and 6 had negative cultures. Among the 30 positive cases, sequencing of
      16S rDNA permitted identification of species (18), genus (8), or neither (4);
      sodAint and rpoBint sequencing was necessary for species identification in 8
      cases. Species identifications were identical in only 61.5%, when conventional
      techniques and DNA sequencing were used. In five of the six blood culture
      negative endocarditis cases, sequencing identified Bartonella quintana (3), B.
      henselae (1), and Streptococcus gallolyticus (1). Our results demonstrate a clear
      benefit of molecular identification, particularly in cases of blood culture
      negative endocarditis and of possible endocarditis, to confirm or invalidate the
      diagnosis. Moreover, in 19.4% of the definite cases, the improvement in species
      identification by sequencing led to improved patient management.

PMID- 14720394
TI  - Emerging genotype (GGIIb) of norovirus in drinking water, Sweden.
AB  - From May through June 2001, an outbreak of acute gastroenteritis that affected at
      least 200 persons occurred in a combined activity camp and conference center in
      Stockholm County. The source of illness was contaminated drinking water obtained
      from private wells. The outbreak appears to have started with sewage pipeline
      problems near the kitchen, which caused overflow of the sewage system and
      contaminated the environment. While no pathogenic bacteria were found in water or
      stools specimens, norovirus was detected in 8 of 11 stool specimens and 2 of 3
      water samples by polymerase chain reaction. Nucleotide sequencing of amplicons
      from two patients and two water samples identified an emerging genotype
      designated GGIIb, which was circulating throughout several European countries
      during 2000 and 2001. This investigation documents the first waterborne outbreak
      of viral gastroenteritis in Sweden, where nucleotide sequencing showed a direct
      link between contaminated water and illness.

PMID- 14720395
TI  - Mycobacterium tuberculosis Beijing genotype.
AB  - Molecular epidemiologic studies of strains of Mycobacterium tuberculosis are
      currently conducted worldwide. The genetically distinct Beijing family of strains
      has been associated with large outbreaks of tuberculosis, increased virulence,
      and multidrug resistance. However, in this first population-based search for
      Beijing strains in the Danish DNA fingerprint database, analysis of 97% of all
      culture-positive tuberculosis patients in 1992 to 2001 showed that 2.5% of 3,844
      patients, 1.0% of Danish-born patients, and 3.6% of immigrants (from 85
      countries) had Beijing strains. No Beijing strains were found among 201 strains
      from Danish-born patients sampled in the 1960s, and no evidence of an increase in
      Beijing strains was found over time. The true prevalence of Beijing strains
      worldwide is unknown because only a fraction of global strains have been
      analyzed.

PMID- 14720396
TI  - Trypanosoma cruzi in persons without serologic evidence of disease, Argentina.
AB  - Current diagnosis of chronic Chagas disease relies on serologic detection of
      specific immunoglobulin G against Trypanosoma cruzi. However, the presence of
      parasites detected by polymerase chain reaction (PCR) in patients without
      positive conventional serologic testing has been observed. We determined the
      prevalence and clinical characteristics of persons with seronegative results and
      T. cruzi DNA detected by PCR in a population at high risk for chronic American
      trypanosomiasis. We studied a total of 194 persons from two different
      populations: 110 patients were recruited from an urban cardiology clinic, and 84
      persons were citizens from a highly disease-endemic area. Eighty (41%) of persons
      had negative serologic findings; 12 (15%) had a positive PCR. Three patients with
      negative serologic findings and positive PCR results had clinical signs and
      symptoms that suggested Chagas cardiomyopathy. This finding challenges the
      current recommendations for Chagas disease diagnosis, therapy, and blood
      transfusion policies.

PMID- 14720397
TI  - Risk factors for norovirus, Sapporo-like virus, and group A rotavirus
      gastroenteritis.
AB  - Viral pathogens are the most common causes of gastroenteritis in the community.
      To identify modes of transmission and opportunities for prevention, a case
      control study was conducted and risk factors for gastroenteritis attributable to
      norovirus (NV), Sapporo-like virus (SLV), and rotavirus were studied. For NV
      gastroenteritis, having a household member with gastroenteritis, contact with a
      person with gastroenteritis outside the household, and poor food-handling hygiene
      were associated with illness (population attributable risk fractions [PAR] of
      17%, 56%, and 47%, respectively). For SLV gastroenteritis, contact with a person
      with gastroenteritis outside the household was associated with a higher risk (PAR
      60%). For rotavirus gastroenteritis, contact with a person with gastroenteritis
      outside the household and food-handling hygiene were associated with a higher
      risk (PAR 86% and 46%, respectively). Transmission of these viral pathogens
      occurs primarily from person to person. However, for NV gastroenteritis,
      foodborne transmission seems to play an important role.

PMID- 14720398
TI  - Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.
AB  - During 1999 to 2000, we identified HIV-infected persons with new episodes of
      tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other
      Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%)
      of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative
      or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were
      concentrated at three hospitals that treat the greatest numbers of HIV-infected
      persons with TB. Of patients with TB, those with HIV infection differed from
      those without known HIV infection in having more frequent prior exposure to
      clinical services and more frequent previous TB therapy or prophylaxis. However,
      MDR-TB in HIV-infected patients was not associated with previous TB therapy or
      prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care
      in public hospitals in Lima and Callao; they represent sentinel cases for a
      potentially larger epidemic of nosocomial MDR-TB.

PMID- 14720399
TI  - Human monocytotropic ehrlichiosis, Missouri.
AB  - To determine the incidence, clinical and laboratory characteristics, and utility
      of molecular diagnosis of human monocytotropic ehrlichiosis (HME) in the primary
      care setting, we conducted a prospective study in an outpatient primary care
      clinic in Cape Girardeau, Missouri. One hundred and two patients with a history
      of fever for 3 days (>37.7 degrees C), tick bite or exposure, and no other
      infectious disease diagnosis were enrolled between March 1997 and December 1999.
      HME was diagnosed in 29 patients by indirect immunofluorescent antibody assay and
      polymerase chain reaction (PCR). Clinical and laboratory manifestations included
      fever (100%), headache (72%), myalgia or arthralgia (69%), chills (45%), weakness
      (38%), nausea (38%), leukopenia (60%), thrombocytopenia (56%), and elevated
      aspartate aminotransferase level (52%). Hospitalization occurred in 41% of case
      patients. PCR sensitivity was 56%; specificity, 100%. HME is a prevalent,
      potentially severe disease in southeastern Missouri that often requires
      hospitalization. Because clinical presentation of HME is nonspecific, PCR is
      useful in the diagnosis of acute HME.

PMID- 14720400
TI  - Mycobacterium abscessus and children with cystic fibrosis.
AB  - We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years;
      range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in
      respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium
      abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients
      (6 male, 9 female; mean age 11.9 years; range 2.5-22 years) had at least one
      positive sample for this microorganism (versus 6 patients positive for M. avium
      complex), including 10 with >3 positive samples (versus 3 patients for M. avium
      complex). The M. abscessus isolates from 14 patients were typed by pulsed-field
      gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out
      a common environmental reservoir or person-to-person transmission. Water samples
      collected in the cystic fibrosis center were negative for M. abscessus. This
      major mycobacterial pathogen in children and teenagers with cystic fibrosis does
      not appear to be acquired nosocomially.

PMID- 14720401
TI  - The rabbit as a new reservoir host of enterohemorrhagic Escherichia coli.
AB  - We investigated the prevalence of enterohemorrhagic Escherichia coli (EHEC) in
      rabbits acquired from two commercial vendors and a local petting zoo. Fecal
      samples from 34 Dutch Belted (DB) and 15 New Zealand White (NZW) rabbits were
      cultured; and isolates were biotyped, serotyped, tested by polymerase chain
      reaction (PCR), and genotyped by repetitive-element sequence-based PCR (Rep-PCR).
      Seven (25%) of 28 DB rabbits acquired from one commercial source were positive
      for EHEC, including O153:H- and O153:H7. One (9%) of 11 NZW rabbits from the same
      source was positive for eae-, stx1+ O153 strains. In contrast, six DB rabbits
      from another commercial source and four rabbits from a petting zoo were negative
      for EHEC. Rep-PCR demonstrated that the O153 EHEC and O145 enteropathogenic E.
      coli were two distinct clones. Our study indicates that rabbits are a new
      reservoir host of EHEC that may pose a zoonotic risk for humans.

PMID- 14720402
TI  - West Nile virus in Mexico: evidence of widespread circulation since July 2002.
AB  - West Nile virus (WNV) antibodies were detected in horses from five Mexican
      states, and WNV was isolated from a Common Raven in the state of Tabasco.
      Phylogenetic studies indicate that this isolate, the first from Mexico, is
      related to strains from the central United States but has a relatively high
      degree of sequence divergence.

PMID- 14720403
TI  - Severe acute respiratory syndrome epidemic in Asia.
AB  - We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS)
      cases in Singapore, Hong Kong, and Beijing using the Richards model. The
      predicted total SARS incidence was close to the actual number of cases; the
      predicted cessation date was close to the lower limit of the 95% confidence
      interval.

PMID- 14720404
TI  - Age and variant Creutzfeldt-Jakob disease.
AB  - The young and stable median age of those who die of variant Creutzfeldt-Jakob
      disease has been attributed to age-dependent infection rates. This analysis shows
      that an influence of age on risk for death after infection better explains age
      patterns, suggesting that biologic factors peaking in the third decade of life
      may hasten disease.

PMID- 14720405
TI  - Noninvasive method for monitoring Pneumocystis carinii pneumonia.
AB  - The progression of Pneumocystis carinii pneumonia was temporally monitored and
      quantified by real-time polymerase chain reaction of P. carinii-specific DNA in
      oral swabs and lung homogenates from infected rats. DNA levels correlated with
      the number of P. carinii organisms in the rats' lungs, as enumerated by
      microscopic methods. This report is the first of a noninvasive, antemortem method
      that can be used to monitor infection in a host over time.

PMID- 14720406
TI  - Visceral leishmaniasis treatment, Italy.
AB  - First-line drug treatment was recorded in 573 immunocompetent patients with
      visceral leishmaniasis in Italy. In the past 12 years, the proportion of
      antimonial treatments decreased from 100% to 2.8%, while the proportion of
      amphotericin B treatments increased from 0% to 97.2%. The countrywide change in
      therapy is a response to both disease reemergence and increasing antimonial
      failure.

PMID- 14720407
TI  - Ciprofloxacin treatment failure in typhoid fever case, Pakistan.
AB  - We report a case of ciprofloxacin treatment failure in a typhoid fever patient at
      a tertiary care hospital in Rawalpindi, Pakistan. This case shows not only the
      emergence of fluoroquinolone resistance in typhoid salmonellae but also the
      inadequacy of the current laboratory guidelines for detection of this resistance.

PMID- 14720408
TI  - Novel lyssaviruses isolated from bats in Russia.
AB  - Two new rabies-related viruses were discovered in Russia during 2002. Viruses
      were isolated from bats in Eastern Siberia near Baikal Lake and in the western
      Caucasus Mountains. After preliminary antigenic and genetic characterization, we
      found that both viruses should be considered as new putative lyssavirus
      genotypes.

PMID- 14720409
TI  - Human metapneumovirus and respiratory syncytial virus, Brazil.
AB  - We describe the epidemiologic and clinical characteristics of 111 children
      attending clinics and hospitals in Aracaju, northeast Brazil, with acute
      respiratory infections attributable to human metapneumovirus (HMPV), respiratory
      syncytial virus (RSV), or both in May and June 2002. Fifty-three (48%) children
      were infected with RSV alone, 19 (17%) with HMPV alone, and 8 (7%) had RSV/HMPV
      co-infections.

PMID- 14720410
TI  - Actinomyces odontolyticus bacteremia.
AB  - We describe two immunosuppressed female patients with fever and Actinomyces
      odontolyticus bacteremia, a combination documented once previously in an
      immunocompetent male patient. The patients were treated with doxycycline and
      clindamycin; these drugs, with beta-lactams, are effective treatment for A.
      odontolyticus infections.

PMID- 14720411
TI  - Mycobacterium tuberculosis Beijing genotype and risk for treatment failure and
      relapse, Vietnam.
AB  - Among 2,901 new smear-positive tuberculosis cases in Ho Chi Minh City, Vietnam,
      40 cases of treatment failure and 39 relapsing cases were diagnosed. All initial
      and follow-up Mycobacterium tuberculosis isolates of these case-patients had
      (nearly) identical restriction fragment length polymorphism patterns, and the
      Beijing genotype was a significant risk factor for treatment failure and relapse
      (odds ratio 2.8, 95% confidence interval 1.5 to 5.2).

PMID- 14720412
TI  - Baylisascaris procyonis in the metropolitan Atlanta area.
AB  - Baylisascaris procyonis, the raccoon roundworm responsible for fatal larva
      migrans in humans, has long been thought to be absent from many regions in the
      southeastern United States. During spring 2002, 11 (22%) of 50 raccoons trapped
      in DeKalb County, Georgia, had B. procyonis infection. The increasing number of
      cases highlight this emerging zoonotic infection.

PMID- 14720413
TI  - Scrub typhus reemergence in the Maldives.
AB  - In summer 2002, an outbreak of febrile illness began in the Maldives in the
      Indian Ocean. Through April 2003, officials recorded 168 cases with 10 deaths.
      The Armed Forces Research Institute of Medical Sciences in Bangkok confirmed
      Orientia tsutsugamushi and conducted a joint investigation with the Ministry of
      Health, Maldives. These cases of scrub typhus were the first in the Maldives
      since World War II.

PMID- 14720414
TI  - Chlamydophila abortus pelvic inflammatory disease.
AB  - We report the first documented case of an extragestational infection with
      Chlamydophila abortus in humans. The pathogen was identified in a patient with
      severe pelvic inflammatory disease (PID) by sequence analysis of the ompA gene.
      Our findings raise the possibility that Chlamydiaceae other than Chlamydia
      trachomatis are involved in PID.

PMID- 14720415
TI  - [One-stage urethroplasty using colonic mucosa in the treatment of complex lengthy
      urethral stricture].
AB  - OBJECTIVE: To investigate the feasibility of urethral reconstruction with colonic
      mucosa graft in the treatment of complex lengthy urethral stricture. METHODS:
      Between October 2000 and May 2003, 19 male patients with complex lengthy urethral
      stricture that had undergone unsuccessful urethral repair 3 times on average,
      aged 18 - 65, were treated with free graft of colonic mucosa 10 to 17 cm (mean
      13.2 cm) long. The patients were followed-up for 6 - 36 months (17 months on
      average) by retrograde urethrography, urethroscopy, and uroflometry. RESULTS:
      Meatal stenosis that needed reoperation was developed in 1 patient 3 months
      postoperatively. This patient became voiding very well with a urinary peak flow
      of 28.7 ml per second during the follow-up of 12 months after the second
      operation. Hyperplasia of verumontanum was observed during urethroscopy in 1
      patient 14 months postoperatively. Uroflometry examination showed a urinary peak
      flow of 46.5 ml/s after transurethral colliculectomy. The other 17 patients were
      voiding well with a urinary peak flow greater than 15 ml/s (16 to 28.5 ml/s).
      CONCLUSION: Colonic mucosa graft urethroplasty is a feasible procedure for the
      treatment of complex lengthy urethral stricture, particularly when the more
      conventional options fail or are contraindicated.

PMID- 14720416
TI  - [Operative outcome and experience in arteriovenous shunt at different sites].
AB  - OBJECTIVE: To summarize and analyze the influencing factors of both success and
      half-year patency rate of radial artery-cephalic vein arteriovenous fistula.
      METHODS: A retrospective analysis was made on the clinical data of 102 patients
      with chronic renal failure undergoing radial artery-cephalic vein arteriovenous
      shunt for hemodialysis during 7 years and the influence of different factors:
      sex, age, primary disease, incision site, and situations of vessels on the
      operative success rate and the half-year patency rate of the fistula was
      compared. RESULTS: No significant difference in the initial success rate of
      operation was found between the operations performed at the two different
      incision sites: at the wrist and at anatomist's snuffbox. However, the operation
      at the wrist was better than that at anatomist's snuffbox with regard to the half
      year patency rate. Both operative success rate and half-year patency rate were
      not influenced by patient's sex, age, and primary disease. Anastomotic
      hyperplasia, condition of blood vessel and anastomotic technique were important
      factors influencing the operative failure and fistula occlusion. CONCLUSION:
      Correct selection of incision site is of key importance for both operative
      success and maintenance of half-year patency of radial artery-cephalic vein
      arteriovenous fistula. In addition, anastomotic hyperplasia, diameter and intimal
      smoothness of selected blood vessel, condition of run-off vessel, operative
      technique, anastomotic angle, distance between artery and vein, and patient's
      self-protection are also considered important influencing factors.

PMID- 14720417
TI  - [Association between tryptophan hydroxylase gene polymorphisms and attention
      deficit hyperactivity disorder with or without learning disorder].
AB  - OBJECTIVE: To investigate the relationship between two tryptophan hydroxylasec
      (TPH) gene polymorphisms, A218C and A-6526G polymorphisms, and attention deficit
      hyperactivity disorder (ADHD) with or without learning disorder (LD). METHODS:
      Blood samples were taken from 132 trios with probands of ADHD with LD and 221
      trios with probands of ADHD without LD. DNA was extracted and PCR was performed
      to amplify the fragments of A218C amd A-6526G polymorphisms. NheI and MboI were
      used to detect different alleles of the two polymorphisms separately.
      transmission disequilibriumtest (TDT) and haplotype analysis were used to test
      the association of the two polymorphisms of TPH gene and ADHD with or without LD.
      RESULTS: Haplotype block composed by A218C and A-6526G polymorphisms was related
      to ADHD with LD (chi(2) = 9.362, df = 3, P = 0.025). The haplotype of 218A/-6526G
      was significantly untransmitted to the probands with ADHD with LD (chi(2) =
      9.252, df = 1, P = 0.002). CONCLUSION: TPH gene and the haplotype of 218A/-6526G
      may be related to ADHD with LD.

PMID- 14720418
TI  - [Association of -2548G/A functional polymorphism in the promoter region of leptin
      gene with antipsychotic agent-induced weight gain].
AB  - OBJECTIVE: To investigate whether the -2548G/A functional polymorphism in
      promoter region of leptin gene influencing weight gain following antipsychotic
      agents (APS) acute treatment in schizophrenic patients. METHODS: 128 Chinese Han
      untreated patients with schizophrenia (male 61, female 67) with an age and gender
      matched health controls (n = 38) were recruited. The polymorphism of leptin gene
      was determined with PCR-RFLP technique. MRI determined abdominal body fat in 22
      controls and 30 patients on admission and after 10 weeks treatment with
      risperidone or chlorpromazine. Body mass index (BMI) was measured on admission
      and every week subsequently (for patients). RESULTS: There were average increases
      in (6.2 +/- 5.7)% of baseline weight and in (38.5 +/- 42)% of baseline abdominal
      subcutaneous fat (SUB) and in (40.0 +/- 41.2)% of baseline intra-abdominal fat
      (IAF) 10 weeks after treatment. There were no significant differences in the
      distribution of allele and genotypes either between the patients and controls or
      between gender groups. It was found significantly increased weight gain in the
      patient with the -2548AA genotype (chi(2) = 7.529, df = 1, P = 0.006; OR = 1.941;
      95% CI: 1.175 - 3.207); The genotypes had no influence on the baseline weight
      indicators both in patients and controls. However, as compared with the patients
      with G allele, the patients with AA genotype had significant increase in BMI (P =
      0.003) and SUB (P = 0.009). CONCLUSION: The finding identify that the -2548G/A
      polymorphism in promoter region of leptin gene associated with APS-induced weight
      gain and abdominal fat deposition and distribution. -2548AA may be a genetic risk
      factor for the development of weight gain and body fat deposition in Chinese Han
      schizophrenic patients during APS acute treatment.

PMID- 14720419
TI  - [Association between NAD(P)H: quinone oxidoreductase and apolipoprotein E gene
      polymorphisms in Alzheimer's disease].
AB  - OBJECTIVE: To assess the association between NAD(P)H: quinone oxidoreductase 1
      (NQO1) C609 T allele and apolipoprotein E (ApoE) polymorphism and sporadic
      Alzheimer disease (SAD). METHODS: The polymorphisms of NQO1 and ApoE gene were
      determined by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) method in 92 SAD patients and 108 normal controls, all of Han
      nationality. RESULTS: The frequencies of mutant T allele and T/C + T/T genotype
      at nucleotide position 609 of NQO1 gene were 56% and 89% respectively in the
      patients with SAD, significantly higher than those in the controls (45% and 71%
      respectively) with an odds ratio of 1.56 (for mutant T allele) and of 3.301 (for
      genotype) respectively. The frequency of the ApoE2 allele was significantly lower
      in the SAD patients than in the controls (chi(2) = 3.753, P < 0.05) and the
      frequency of ApoE4 was higher in the SAD patients, however, without a
      statistically significant difference (chi(2) = 1.863, P = 0.172). No significant
      interaction was found between NQO1 C609T and ApoE polymorphisms in SAD patients.
      CONCLUSION: NQO1 C609T may be an independent genetic risk factor for SAD in
      Chinese.

PMID- 14720420
TI  - [The distributive characteristics of impaired glucose metabolism subcategories in
      Chinese adult population].
AB  - OBJECTIVE: To clarify the frequencies and clinical features of different impaired
      glucose metabolism subcategories in Chinese adults. METHODS: A cross-sectional
      analysis of the data of 15,637 Chinese adults (aged >or= 25 years) who underwent
      standard 75 g oral glucose tolerance test from the National Diabetes Mellitus
      Survey (1994) was conducted. According to the 1999 WHO criteria for diabetes, the
      subjects were divided into 7 groups: normal glucose tolerance (NGT, FPG < 6.1
      mmol/L and PG 2 h < 7.8 mmol/L), isolated impaired fasting glucose (i-IFG, 6.1
      <or= FPG < 7.0 mmol/L and PG 2 h < 7.8 mmol/L), isolated impaired glucose
      tolerance (i-IGT, FPG < 6.1 mmol/L and 7.8 <or= PG 2 h < 11.1 mmol/L), combined i
      IFG and i-IGT (IFG/IGT, 6.1 <or= FPG < 7.0 mmol/L and 7.8 <or= PG 2 h < 11.1
      mmol/L), isolated fasting hyperglycemia (IFG, FPG >or= 7.0 mmol/L and PG 2 h <
      11.1 mmol/L), isolated postload hyperglycemia (IPH, FPG < 7.0 mmol/L and PG 2 h
      >or= 11.1 mmol/L), and combined IFH and IPH (IFH/IPH, FPG >or= 7.0 mmol/L and PG
      2 h >or= 11.1 mmol/L). The frequencies of the above subcategories were calculated
      and the clinical characteristics were compared. RESULTS: (1) The frequencies of
      NGT, i-IFG, i-IGT, IFG/IGT, IFG, IPH, and IFH/IPH were 50.8%, 8.8%, 12.3%, 6.1%,
      6.4%, 5.2%, and 10.4% respectively. (2) The frequencies of i-IGT, IFG/IGT, IPH,
      and IFH/IPH increased with age, whereas the frequencies of i-IFG and IFH tended
      to plateau in the age groups of 25 - 34 years and 55 - 64 years. (3) The mean age
      and blood pressure were significantly lower in the i-IFG group (vs the i-IGT or
      IFG/IGT group) and the IFH group (vs IPH or IFH/IPH group). Compared with the IPH
      group, the IFH group had higher homeostasis model assessment (HOMA) insulin
      resistance index (HOMA-IR) and lower beta cell function index (BCI). CONCLUSIONS:
      i-IGT is the most common impaired glucose regulation (IGR) subcategory, and
      IFH/IPH is the most common diabetes subcategory in Chinese adults. The
      frequencies of i-IGT and IFH/IPH increase with age. The clinical features of i
      IFG (IFG) are greatly different from those of i-IGT (IPH), suggesting that the
      determinants of FPG and PG 2 h differ.

PMID- 14720421
TI  - [The associations of the single nucleotide polymorphisms on TNF and CD14
      promoters with the mortality of infection, systematic inflammatory response
      syndromec and sepsis in surgical patients].
AB  - OBJECTIVE: To investigate the association of Single nucleotide polymorphism
      (SNPs) tumor necrosis factor (TNF) and CD14 promoter with the systematic
      inflammatory response syndromec (SIRS) and sepsis in surgical patients. METHODS:
      The DNA and RNA sample of PBMC from 113 patients, 40 of them being complicated
      with sepsis, and 100 healthy volunteers were extracted. The SNP genotypes of TNF
      alpha -308 G/A, -863 C/A, CD14-159C/T and TNFB1/B2 were examined by restriction
      fragment length polymorphism PCR (PCR-RFLP). The expressions of TNF-alpha mRNA of
      PBMC in parts of the patients who have at least one genotype of SNP were detected
      by RT-PCR. The risks for sepsis associated with polymorphisms in the TNF-alpha or
      CD14 promoter were determined by multivariate analysis. RESULTS: The rates of
      TNF2, -863A, CD14-159T alleles were 15%, 32.5%, and 40% respectively in patients
      with sepsis, significantly higher than those in the patients with SIRS (8.9%,
      22%, and 23.3%), and those in the healthy volunteers (5%, 16% and 26%). The
      expression of TNF-alpha mRNA was much higher in those patients with at least one
      kind of SNP than those without SNP. CONCLUSION: The A-allele at the -308 and -863
      position in the TNF-alpha promoter and the T-allele at the -159 position in the
      CD14 promoter increase the risk for sepsis. The effect of SNP genotypes on TNF
      alpha expression can modulate inflammatory response.

PMID- 14720422
TI  - [Pathologic study of circulating blood leukocytes in severe acute respiratory
      syndrome].
AB  - OBJECTIVE: To study the pathologic characteristics and pathogenesis of
      circulating blood leucocytes infected by severe acute respiratory syndrome
      associated coronavirus (SARS CoV or SCV) in SARS patients. METHODS: Blood samples
      of 22 SARS patients were studied, and 4 healthy blood samples were observed as
      negative controls. The white blood cells were collected from whole blood. The
      ultrastructural characteristics were observed by transmission electron
      microscopy. CD45RO antibody was used for pre-embedding immunoelectron microscopy.
      The SARS viral sequence was detected with real-time polymerase chain reaction (RT
      PCR). RESULTS: Coronavirus-like particles were founded in the leukocytes in 6 of
      the 22 blood samples. Five of them gave positive results in the real-time PCR.
      The number of granulocytes was increased (P < 0.05) and that of lymphocytes was
      decreased (P < 0.05) respectively. Immunoelectron microscopy showed that CD45RO
      positive T lymphocyte decreased to 6% - 7%. Circulating lymphocytes had the
      highest percentage of infection. The morphologic characteristics of coronavirus
      like particles were spherical or oval in shape, about 80 - 120 nm in diameter,
      with a dense round core and a clear halo around the core. A distinct membrane and
      club-shaped surface projections were seen in the periphery. The particles were
      located in the cytoplasm, the cisternae of endoplasmic reticulum, Golgi apparatus
      and vesicles. Virus entered cells by endocytosis or membrane fusion and was
      released through a budding process. CONCLUSION: Our data suggested that
      lymphocytes, particularly T cells, were probably the target cells of SARS CoV.
      The viruses may actively infected the immune cells during SARS CoV acute
      infection phase and the destruction of target cells may be one of the important
      reasons for the death of the circulating leukocytes in SARS.

PMID- 14720423
TI  - [Effect of universal salt iodization on the dosage of antithyroid drug].
AB  - OBJECTIVE: To investigate the effect of universal salt iodization (USI) on
      antithyroid drug. METHODS: One hundred and one patients with untreated
      hyperthyroidism were randomly divided into two sex and age-matched groups: group
      A (n = 45, consuming pure salt without iodine) and group B (n = 56, consuming
      iodated salt). The same dosage of 300 mg propylthiouracil (PTU) was given to both
      groups at beginning, the serum TT4. TT3, FT4, FT3, and TSH were measured before
      and 1, 2, 3, 6 months after PTU treatment, when the serum TT4, TT3, FT4. FT3, and
      TSH were back to the normal ranges, the dosage of PTU was decreased to maintain
      the normal levels of serum thyroid hormones. RESULTS: The urine iodine and serum
      thyroid hormone levels were not significantly different between group A and group
      B before the treatment (P > 0.05). The urine iodine of group A was significant
      lower 2 - 3 months after the treatment (148.4 micro g/L) than before the
      treatment (213.4 micro g/L, P < 0.01). There were not significant differences in
      serum TT4, TT3, FT4, and FT3 between group A and B before the treatment (all P >
      0.05). One month after the treatment the serum TT4 and TT3 in group A were (153
      +/- 50) nmol/L and (3.6 +/- 1.2) nmol/L respectively, both significantly lower
      than those of the group B [(177 +/- 64) nmol/L and (2.7 +/- 1.5) nmol/L
      respectively, P = 0.041 and 0.033], however, there was no significant difference
      in other serum thyroid hormones between the group A and group B. The dosage of
      PTU was not significantly different between group A and B 1 month after the
      treatment, but became significantly higher in group B than in group A 2, 3, and 6
      months after the treatment (214,189, and 178 mg/d respectively vs. 190, 147, and
      116 mg/d respectively, and 24, 42, and 62 mg/day more respectively, all P <
      0.05). CONCLUSION: Hyperthyroidism can be effectively controlled by PTU while the
      patients consume iodated salt, but the dosage of PUT needed should be higher than
      while the patients consume pure salt.

PMID- 14720424
TI  - [Study on lung carcinogenesis associated genes in human lung squamous cell
      carcinoma and malignant transformation of human bronchial epithelial cells
      induced by carcinogen].
AB  - OBJECTIVE: To investigate lung carcinogenesis associated genes in human lung
      squamous cell carcinoma and malignant transformation of human bronchial
      epithelial cells induced by chemical carcinogens with cDNA microarray. METHODS:
      The gene expression patterns were detected in all specimens by cDNA microarray
      which representing 4 096 different human genes. The differences in gene
      expression among 6 cases of human lung squamous cell carcinoma tissues and 6
      normal lung tissues were analyzed. The different gene expression patterns between
      the normal human bronchial epithelial cell lines (16HBE) and the malignant
      transformation of human bronchial epithelial cells induced by Benzo(a)pyrene
      metabolite BPDE (anti-Benzo(a)pyrene diol-epoxide,BPDE) and crystalline nickel
      sulfide were also studied by that method. The similar changed genes among those
      gene expression patterns were identified as lung carcinogenesis associated genes.
      RESULTS: Among the 4096 genes of cDNA microarrays, there were 171 genes expressed
      differently among lung cancer tissues and normal lungs, 143 genes expressed
      differently between BPDE transformed cells and normal 16HBE cell lines, 151 genes
      differed between nickel sulfide transformed cells and normal 16HBE cell lines. By
      comparing the gene expression profiles, there were 89 similar changed genes which
      might be associated with human lung carcinogenesis, 39 of which were up
      regulated: 6 oncogenes, 4 cell cycle control genes, 6 cell proliferation genes, 8
      metastasis genes, 3 neuroendocrine genes, 1 drug-resister gene, 1 anti-apoptosis
      gene, 1 oxidative gene and other 9 genes. 50 genes were down-regulated: 7 tumor
      suppression genes, 11 DNA repair genes, 1 antioxidant genes, 3 GST family genes,
      3 cell framework genes, 2 apoptosis induced genes, 5 signal conduction genes, 5
      cytokines and their receptor genes, 7 metabolization genes, 1 cell matrix genes,
      and other 5 genes. CONCLUSION: cDNA microarray can be applied to study gene
      expression profiles effectively and to screen human lung carcinogenesis
      associated genes.

PMID- 14720425
TI  - [Experimental study of biocompatibility of LIFEs in peripheral fascicles].
AB  - OBJECTIVE: To study the biocompatibility of longitudinally implanted
      intrafascicular electrodes (LIFEs) in a rabbit sciatic nerve model. And to
      discuss the possibility of peripheral fascicular signals as a new signal source
      to control an electronic prosthetic hand. METHODS: LIFEs were implanted
      chronically into sciatic peripheral fascicles of rabbits as recording and
      stimulating electrodes. Motor-evoked potentials (MEP) and cortical somatosensory
      evoked potentials (CSEP) were recorded by using a transcranial stimulation system
      (TCS) over six-month period to observe the change of the signals recorded. At the
      end of the experiments, the fascicles at the electrodes implanted site were
      anatomized for histological examination under light microscope and transmission
      electron microscope. In human test, LIFEs were implanted into radial nerve, ulnar
      nerve and medial nerve of an amputee volunteer. Signals were detected when the
      volunteer was asked to do different movements of his missing hand, and the
      signals recorded by LIFEs were used to control an electronic prosthetic hand.
      RESULTS: The difference of onset latency (OL) of MEP and CSEP recorded at
      different time has remarkable statistical significance (one way ANOVA, P <
      0.001). After multiple comparisons, onset latency (OL) of MEP and CSEP had no
      obvious change during 1 month, but significantly increased in the later time, and
      then became stable after 3 months after implantation. The difference of the
      interpeak amplitudes (IPAs) of MEP recorded at different time has remarkable
      statistical significance (one way ANOVA, P < 0.001). The interpeak amplitudes
      (IPAs) of MEP had no distinct change during 1 month, but significantly decreased
      over the next period, and then became stable after 3 months. Though the interpeak
      amplitudes (IPAs) of CSEP decreased slowly over six-month period of the study,
      the difference has no statistic significance (one way ANOVA, P > 0.05). At the
      end of experiment, histological examination indicated that a typical foreign body
      reaction developed and electrodes caused a mild damage to fascicles. But
      inflammatory cells and neuroma were not seen around the electrodes. Signals
      recorded by LIFEs planted in proximal radial, ulnar and median nerve of the
      amputated arm were different when the amputee volunteer was ordered to do some
      different movements with his mind. Some signals could be used to control the
      seven-freedom electronic prosthetic hand. CONCLUSIONS: Longitudinally implanted
      intrafascicular electrodes (LIFEs) have excellent biocompatibility with
      peripheral fascicles. They can be implanted chronically into fascicles and record
      signals. Furthermore, LIFEs can record physiological signals of peripheral
      fasciculi when hand moves, and these signals could be used to control an
      electronic prosthetic hand through further research.

PMID- 14720426
TI  - [Molecular mechanisms of two novel mutations of factor XIII gene resulting in
      hereditary coagulation deficiency].
AB  - OBJECTIVE: To investigate the mechanisms of two novel missense mutations of
      factor XIIIA subunit gene (Arg77-->Cys,Ser413-->Trp) in the pathogenesis of
      hereditary factor XIII deficiency. METHODS: Site-directed mutagenesis was
      conducted to obtain 2 mutant human XIII A recombinant plasmids, mut-PCI/FXIIIA.
      Normal wild type factor XIII A recombinant plasmid, wt-PCI/FXIIIA, and mut
      PCI/FXIIIA, were transfected into cultured COS7 cells line, renal fibroid cell of
      African green monkey using Superfect reagent respectively, The expression levels
      of DNA, RNA and protein of human factor XIII, both wild type and mutant, were
      detected by PCR, RT-PCR and Western blotting. Pulse-chase experiment was used to
      look into the changing of factor XIII A in the cytoplasm. Factor XIIIA activity
      was assayed by Biotin-pentylamine incorporation technique. RESULTS: The mRNA
      levels of the two mutants in transfected cells were similar to that of the wild
      type factor XIIIA. But the amount of mutant factor XIIIA protein and its activity
      in cells decreased markedly, even disappeared. Pulse-chase experiment revealed
      that at the two mutants existed chase time 0.5 h and 1 h considerable amounts in
      cells and then disappeared rapidly later. CONCLUSION: The 2 mutations of the
      factor XIIIA cause the instability, degradation, and rapid disappearance of
      FXIIIA in cytoplasm, thus resulting in hereditary factor XIII deficiency.

PMID- 14720427
TI  - [Endobronchial eosinophils preferentially stimulate T helper cell type 2
      responses].
AB  - OBJECTIVE: The aim of the present study was to evaluate whether eosinophils
      within the tracheobronchial lumen can stimulate Th2 cell expansion by presenting
      antigen both in vitro and in vivo. METHODS: Airway eosinophils were recovered
      from ovalbumin-sensitized and -challenged BALB/c mice, these eosinophils were
      then cocultured with sensitized CD4(+) cells in the absence or presence of anti
      CD80 or/and -CD86 monoclonal antibodies. Airway eosinophils were instilled into
      the trachea of sensitized mice, At 3 d thereafter, the draining paratracheal
      lymph nodes were removed and teased into cell suspensions for culture. Cell-free
      culture supernatants were collected for detection of cytokines. RESULTS: Our data
      showed that airway eosinophils, recovered following inhalational ovalbumin
      challenge in sensitized mice functioned as CD80- and CD86-dependent antigen
      presenting cells to stimulate sensitized CD4(+) lymphocytes to produce IL-4, IL-5
      and IL-13, but not interferon-gamma (IFN-gamma) in vitro assay. When instilled
      intratracheally in ovalbumin-sensitized recipient mice, these antigen-loaded
      eosinophils migrated into draining paratracheal lymph nodes primed Th2 cells in
      vivo for IL-4, IL-5 and IL-13, but not IFN-gamma, production during the in vitro
      culture that was also CD80- and CD86-dependent. CONCLUSIONS: We concluded that
      eosinophils within the lumina of airways could process inhaled antigen function
      in vitro and in vivo as antigen-presenting cells to promote expansion of Th2
      cells. This investigation highlights the potential of eosinophils to not only act
      as terminal effector cells but also to actively modulate immune responses by
      amplifying Th2 cell responses.

PMID- 14720428
TI  - [Department of a finite element model of the Head Model of HYBRID III Dummy with
      the Human Mandible].
AB  - OBJECTIVE: To analyze the biomechanics of impact injury in the condition of the
      simulate impact on mandible. METHODS: A finite element model of human mandible
      was developed from the CT scan images by the technologies of three-dimensional
      reconstruction, image processing and meshing. The mandible model was connected to
      a modified head model of HYBRID III dummy with joint according to the anatomic
      structure and mechanical characteristics of the temporomandibular joint. RESULTS:
      A finite element model of human head with true anatomic structure mandible has
      been developed. This model has been validated with the cadaver test results. The
      higher stress was showed in the condyle rejoins and coracoid in the model when
      mandible was in impact simulation. CONCLUSIONS: This model can be used to
      research the mechanism of craniofacial blunt-impact injury and assess the injury
      severity. The model of HYBRID III dummy with the human mandible was helpful for
      the boundary design of mandibular model in the impact simulations.

PMID- 14720429
TI  - [An experimental study on airway inflammation and remodeling in a rat model of
      chronic bronchitis and emphysema].
AB  - OBJECTIVE: To study the pathological features of airway inflammation and
      remodeling in rats with chronic bronchitis (CB) and emphysema and to evaluate the
      protective and therapeutic effects of erythromycin (EM). METHODS: Forty-three
      Wistar rats were assigned to eight groups: normal control group (A group, n = 5),
      normal saline solution group (P group, n = 5), CB group (L group, n = 6), CB and
      emphysema group (S group, n = 6), low-dose EM-treatment group (E(1) group, n =
      5), high-dose EM-treatment group (E(2) group, n = 6), low-dose EM-prevention
      group (E(10) group, n = 5) and high-dose EM-prevention group (E(20) group, n =
      5). The rat model of CB and emphysema was established by intratracheal
      instillation of lipopolysaccharide (LPS) and daily exposure to cigarette smog.
      After four weeks, total and differential cell counts in bronchoalveolar lavage
      fluid (BALF) were observed, and the pathomorphological changes in the lung were
      analyzed. The thickness of the smooth muscles and collagen in the bronchial wall
      were measured. Expression and localization of transforming growth factor beta(1)
      (TGF-beta(1)) were observed in the bronchi and lung tissues by
      immunohistochemistry. The levels of hyaluronic acid (HA) and procollagen type III
      (PCIII) in the serum and BALF were determined by the radioimmunoassay (RIA).
      RESULTS: (1) Compared with A group [(0.9 +/- 0.7) x 10(5)/ml], absolute
      neutrophil count in BALF from S group [(17.1 +/- 10.8) x 10(5)/ml] were
      significantly higher (P < 0.01). (2) Both the pathologic scores obtained from the
      S group (329 +/- 114) and P group (67 +/- 25), and the thickness of smooth
      muscles and collagen from S group [(9.6 +/- 2.6)%] and A group [(6.1 +/- 1.8)%]
      were statistically different (P < 0.01, P < 0.05, respectively). Expression of
      TGF-beta(1) in the lung of S group was significantly higher than that in A group.
      (3) The levels of HA [(152.5 +/- 36.3) micro g/ml] and PCIII [(40 +/- 8) micro
      g/ml] in serum and the levels of HA [(94 +/- 35) micro g/ml] and PCIII [(39 +/-
      7) micro g/ml] in BALF in S group were higher than those in A group (P < 0.01).
      (4) After treatment with 100 mg/kg EM, absolute neutrophil count in BALF, the
      pathologic scores, the thickness of smooth muscles and collagen in the bronchi,
      the levels of PCIII and HA in serum and the levels of PCIII and HA in BALF were
      reduced to (2.1 +/- 1.4) x 10(5)/ml, 187 +/- 61, (6.0 +/- 2.3)%, (9.69 +/- 5.61)
      micro g/ml, (63.0 +/- 11.6) micro g/ml, (16 +/- 6) micro g/ml, (52 +/- 12) micro
      g/ml, respectively. Statistical analysis revealed that there were significant
      differences as compared to those of group S (P < 0.05). CONCLUSIONS: Many
      inflammatory cells especially neutrophils and alveolar macrophages might play an
      important role in the airway inflammation of CB and emphysema. Thickening of
      smooth muscles and collagen in the bronchi and the excessive depositions of
      extracellular matrix (ECM) constitute the fundamental pathological characteristic
      of airway remodeling in CB and emphysema. EM may prevent airway inflammation and
      remodeling to some degree.

PMID- 14720430
TI  - [A study of protein kinase C signal pathway in regulating airway smooth muscle
      cell proliferation in asthmatic rats].
AB  - OBJECTIVE: To investigate the role of protein kinase C (PKC) signal pathway in
      airway smooth muscle cell (ASMCs) proliferation in asthmatic rats. METHODS: (1)
      Forty-eight Wistar rats were divided into an asthmatic group (group A) and a
      control group (group B), and then subdivided into group A(1), A(2), A(3) and
      group B(1), B(2), B(3) based on the time of challenge (2, 4, 8 weeks). The
      proliferation of ASMCs isolated from group A and B was examined with cell cycle
      analysis, MTT colorimetric assay and proliferating cell nuclear antigen (PCNA)
      immunocytochemical staining. (2) ASMCs from group A(1) and B(1) were treated with
      PKC agonist PMA and inhibitor Ro-31-8220, and their proliferations were examined.
      (3) The expression of PKC-alpha in group A(1), A(2), A(3) and B(1) was observed
      by immunocytochemical staining and RT-PCR, respectively. RESULTS: (1) The
      percentage of S phase, absorbance (A) value and the expression rate of PCNA
      protein in ASMCs from group A were significantly increased compared to those of
      group B (P < 0.01). (2) Before ASMCs from A(1) group were treated, the percentage
      of S phase, A value and the expression rate of PCNA were (19 +/- 3)%, 0.459 +/-
      0.036, and (80 +/- 10)% respectively; After treated with 10 nmol/L PMA, these
      values reached (27 +/- 4)%, 0.599 +/- 0.078, and (95 +/- 9)% respectively; After
      treated with 50 nmol/L PMA, these values were (14 +/- 3)%, 0.346 +/- 0.038, and
      (53 +/- 8)% respectively; After treatment with Ro-31-8220, these values were (14
      +/- 3)%, 0.343 +/- 0.048, and (49 +/- 8)% respectively. Statistical analysis
      revealed that there were significant differences in the percentage of S phase, A
      value and the expression of PCNA before and after treatment (P < 0.01). After
      treatment with 50 nmol/L PMA, there was a significant difference as compared to
      10 nmol/L PMA treatment (P < 0.01), whereas there was no statistical significance
      as compared to Ro-31-8220 treatment (P > 0.05). (3) Compared with that of group
      B(1) (0.84 +/- 0.07), the ratios of A value of PKC-alpha mRNA in group A(1) (1.08
      +/- 0.06), group A(2) (1.12 +/- 0.05), and group A(3) (1.10 +/- 0.08) were
      significantly increased (P < 0.01). Compared with that of group B(1) (28 +/- 4)%,
      the expression rates of PKC-alpha protein in group A(1) (54 +/- 5)%, group A(2)
      (56 +/- 5)%, and group A(3) (53 +/- 6)% were significantly increased (P < 0.01).
      CONCLUSIONS: Airway smooth muscle cell proliferation increases in asthmatic rats.
      PKC and it's alpha subtype may contribute to this process.

PMID- 14720431
TI  - [The relationship between transforming growth factor-beta1, platelet derived
      growth factor and airway remodeling in eosinophilic bronchitis].
AB  - OBJECTIVE: To study the relationship between the expression of transforming
      growth factor-beta(1) (TGF-beta(1)) and platelet derived growth factor (PDGF) and
      airway remodeling in eosinophilic bronchitis (EB). METHODS: Bronchial biopsy
      specimens were obtained from 12 patients with EB (A group), 10 asthmatic patients
      (B group) and 10 patients (C group) with peripheral lung cancer in early stage.
      The subepithelial basement membrane (SBM) thickness was measured by light
      microscopy using HE staining. The expressions of TGF-beta(1) and PDGF in the
      bronchial mucosa were examined by immunostaining. RESULTS: The SBM of A group
      [(6.3 +/- 1.4) micro m] was significantly thicker than that of C group [(4.1 +/-
      1.2) micro m, P < 0.05], but significantly thinner than that of B group [(8.2 +/-
      1.5) micro m]. The numbers of positive cells for TGF-beta(1) and PDGF in A group
      (59 +/- 9, 47 +/- 7 respectively) and B group (85 +/- 12, 76 +/- 11,
      respectively) were significantly higher than those in C group (31 +/- 4, 20 +/-
      3, respectively), and were positively correlated with SBM thickness (r = 0.76,
      0.52, P < 0.05). CONCLUSION: These results suggest that TGF-beta(1) and PDGF
      expressions in bronchial mucosa may play a role in bronchial subepithelial
      fibrosis in EB patients.

PMID- 14720432
TI  - [Study of the expression and role of adrenomedullin and adrenomedullin receptor
      in patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the expression and role of adrenomedullin (ADM) and
      adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: The first study included 9 COPD patients (group I) and 7
      control patients (group II) who had underwent pulmonary lobe resection. Small
      pulmonary artery remodeling was observed with morphometric analysis. The
      expressions of ADM and ADMR mRNA in lung tissue were examined by hybridization in
      situ. The second study recruited 22 patients with COPD. Cardiac catheterization
      was performed to monitor the changes of hemodynamic parameters and the subjects
      were divided into two groups according to the mean pulmonary artery pressure
      (mPAP): patients without pulmonary hypertension (PH, group A, n = 10) and
      patients with PH (group B, n = 12). The levels of pulmonary arterial plasma ADM
      were measured by radioimmunoassay. Arterial blood gas was also measured. RESULTS:
      (1) In patients underwent pulmonary lobe resection: (1) Morphometry studies
      showed that the ratio of vascular wall thickness to external diameter (MT%) and
      ratio of vascular wall area to total area (MA%) increased in group I (P < 0.01);
      (2) Hybridization in situ showed that ADM/ADMR mRNA expressions were
      significantly higher in pulmonary artery walls of group I as compared with group
      II (P < 0.01). (2) In COPD patients without pulmonary lobe resection, the plasma
      ADM level of group B was significantly higher than that of group A (P < 0.05),
      and the plasma ADM level had a significantly positive correlation with mPAP and
      pulmonary vascular resistance (PVR), but a negative correlation with PaO(2).
      CONCLUSION: ADM may play an important protective role as a local
      autocrine/paracrine factor in the development of COPD and PH.

PMID- 14720433
TI  - [Results of unilateral lung volume reduction surgery in twenty-five patients with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To evaluate the effectiveness of unilateral lung volume reduction
      surgery (LVRS) in patients with chronic obstructive pulmonary disease (COPD).
      METHODS: The follow-up data of 25 patients with COPD who had underwent unilateral
      LVRS between January 1996 to December 2002 in department of thoracic surgery,
      China-Japan friendship hospital were analyzed retrospectively. The operative
      target was determined by pre-operative CT and pulmonary ventilation-perfusion
      (V/Q) scintigraphy. LVRS was performed in 21 patients through video assisted
      thoracoscopy surgery (VATS) or VATS with adjuvant small lateral thoracotomy. In 4
      patients LVRS was performed through posterolateral thoracotomy. Destroyed
      pulmonary tissue was resected by liner stapler or Endo GIA. To evaluate the
      effectiveness of unilateral LVRS, the changing of dyspnea score, pulmonary
      function and the quality of life were analyzed. RESULTS: The postoperative follow
      up interval range was 2 years. The mean postoperative FEV(1) increased by (35 +/-
      9)%, and six minute walking distance (6MWD) increased by (88 +/- 22)%. For
      dyspnea score, among 16 patients with a preoperative grade of IV, 4 patients
      improved to grade I, 12 improved to grade II; among 9 patients with a
      preoperative grade of V, 1 improved to grade I, 1 improved to grade II, 4
      improved to grade III, and the other 3 improved to grade IV. Karnofsky score
      increased by (44 +/- 10) in average. One and two year survival rates was 96% and
      92%, respectively. There was no perioperative death in this group, and the total
      postoperative morbidity was 32%. CONCLUSIONS: Unilateral LVRS shows significant
      clinical benefits for the majority of patients with COPD. It is associated with
      lower operative mortality and morbidity, and has a wide range of indications. The
      key points of the operation are to resect dysfunctional lung tissues as much as
      possible and to prevent pulmonary air leak. Preoperative and postoperative
      breathing training plays a very important role in the postoperative recovering of
      lung function.

PMID- 14720434
TI  - [Comparison of thrombolysis and anticoagulation in pulmonary thromboembolism: a
      meta-analysis].
AB  - OBJECTIVE: To pool the data of studies about thrombolysis in pulmonary
      thromboembolism (PTE) and evaluate the efficacy and safety of thrombolysis.
      METHODS: The randomized clinical trials (RCTs) that compared the efficacy or
      safety of thrombolysis and anticoagulation in massive or submassive PTE were
      chosen from MEDLINE disks from 1966 to May of 2003 and CBM disks from 1978 to May
      of 2003. A meta-analysis was employed to evaluate the results of the two
      therapies. RESULTS: Twelve RCTs including 884 cases were analyzed. Compared with
      anticoagulation, the total OR of mortality and recurrence of patients with PTE
      treated with thrombolysis were 0.975 (95% CI 0.504 - 1.886) and 0.653 (95% CI
      0.378 - 1.127) respectively, non-significant difference (P > 0.05). The total OR
      of bleeding in thrombolysis was 2.461 (95% CI 1.636 - 3.702, P < 0.01).
      CONCLUSIONS: Compared with anticoagulation, thrombolysis cannot reduce the
      mortality or recurrence of PTE. Thrombolysis increases the risk of complication
      of bleeding.

PMID- 14720435
TI  - [Biologic significance of thyroid transcription factor-1 and surfactant protein
      expression in pulmonary sclerosing hemangioma].
AB  - OBJECTIVE: To investigate the biologic significance of thyroid transcription
      factor-1 (TTF-1) and surfactant protein A (SP-A) and SP-B expression in pulmonary
      sclerosing hemangioma (PSH). METHODS: TTF-1, SP-A, SP-B, epithelial membrane
      antigen (EMA), pancytokeratin (AE(1)/AE(3)), vimentin, CK7, CK5/6, calretinin, S
      100, neuron specific enolase (NSE), synaptophysin (Syn), chromogranin A (CgA),
      CD(34), Factor VIII and smooth muscle actin (SMA) in 42 patients with PSH were
      examined with immunohistochemistry, while samples from 10 patients were also
      observed by electron microscope. RESULTS: Histopathologically, PSH mainly
      consisted of both surface lining cuboidal cells and pale polygonal cells. Both of
      them were stained with TTF-1, EMA and vimentin, whereas SP-A, SP-B,
      pancytokeratin and CK7 were only positive in surface lining cuboidal cells. Syn,
      NSE, S-100 and CgA showed scattered positivity in these cells. There was no
      significant difference in the expressions of TTF-1 and EMA between these two cell
      types (P > 0.05), whereas the difference was significant in the expression of
      vimentin (P < 0.01). The ultrastructural features cannot differentiate these two
      cells by electron microscope. CONCLUSIONS: It is suggested that PSH is derived
      from primitive respiratory epithelium, and both surface lining cuboidal cells and
      pale polygonal cells were entity cells of the tumor. Examination of different
      immunohistochemical markers including TTF-1, SP-A, SP-B, pancytokeratin, EMA and
      vimentin is helpful in the diagnosis and differential diagnosis of PSH.

PMID- 14720436
TI  - [A study on oxidative DNA damage and lipid peroxidation in patients with
      tuberculous pleurisy].
AB  - OBJECTIVE: To explore the levels of mononuclear cell oxidative DNA damage and
      lipid peroxidation in patients with tuberculous pleurisy. METHODS: The
      mononuclear cell DNA damages in pleural effusion and peripheral blood of 28
      patients with tuberculous pleurisy and in peripheral blood of 25 healthy persons
      were detected by single cell gel electrophoresis (comet%). The levels of total
      antioxidative capacity (TAC) in supernatant of pleural effusion and blood plasma
      of 28 patients and in blood plasma of 25 healthy persons were measured by o
      phenanthroline colorimetric analysis. The contents of malondialdehyde (MDA) of
      blood plasma from 28 patients and from 25 healthy persons were measured by
      thiobarbituric acid colorimetric analysis. The differences between groups were
      analyzed by t test. RESULTS: The comet percentage of mononuclear cells in pleural
      effusion from patients with tuberculous pleurisy was (41.3 +/- 14.5)%, which was
      significantly higher than that in the peripheral blood (21.2 +/- 4.2)% (P <
      0.01); The level of TAC in supernatant of pleural effusion was (5 172 +/- 1 195)
      U/L, which was lower than that in the blood plasma (8 656 +/- 1 592) U/L (P <
      0.01). There was a negative correlation between the comet percentage of
      mononuclear cells and the level of TAC (r = -0.425, P < 0.05) in pleural
      effusion. The comet percentage of mononuclear cells in peripheral blood and the
      content of MDA in blood plasma from patients were (21.2 +/- 4.2)% and (8.25 +/-
      1.37) micro mol/L, which were significantly higher than those from the controls
      (8.9 +/- 3.7)% and (4.46 +/- 0.93) micro mol/L respectively (P < 0.01); The level
      of TAC in blood plasma was (8 656 +/- 1 592) U/L, which was lower than that from
      the controls (10 610 +/- 1 399) U/L (P < 0.01). There were negative correlations
      between the level of TAC in blood plasma and the comet percentage of mononuclear
      cells in peripheral blood or the content of MDA in blood plasma (r = -0.438, 
      0.413, P < 0.05), and there was a positive correlation between the comet
      percentage of mononuclear cells in peripheral blood and the content of MDA in
      blood plasma (r = 0.899, P < 0.01). CONCLUSION: There is oxidation/antioxidation
      imbalance in patients with tuberculous pleurisy, namely oxidative stress, with
      inadequate total antioxidative capacity, particularly in the diseased pleural
      cavity.

PMID- 14720437
TI  - [Establishment of a method with micro-channel electrophoresis for detecting the
      mutations of isoniazid-resistant genes in Mycobacterium tuberculosis].
AB  - OBJECTIVE: To establish a method for the detection of isoniazid resistance
      associated mutations in katG gene and inhA gene in Mycobacterium tuberculosis
      with single-stranded conformation polymorphism (SSCP) analysis by the micro
      channel electrophoresis chip system. METHODS: The polymer solutions of acrylamide
      and its derivatives were used for sieving matrices with small amount of acridine
      orange as the fluorescent tag. A novel pair of primers was designed to link an
      extra segment that could be base paired with the mutation region to the PCR
      products of wild type inhA gene, which made the single strands of wild type inhA
      fragments present a unique conformation. RESULTS: The wild type fragments of katG
      gene and the fragments with mutation at codon 315 can be distinguished, and the
      inhA fragments with wild type and mutated regulatory sequence can be
      distinguished by this method. Twenty-two out of the 23 resistant strains were
      detected from 30 clinical isolates, the efficiency being 95%. CONCLUSION: It is
      demonstrated the high speed and sensitivity in detecting the mutations of
      isoniazid-resistant genes in Mycobacterium tuberculosis by micro-channel
      electrophoresis, and this method may be applicable in clinical detection of
      isoniazid-resistant strains.

PMID- 14720438
TI  - [Detection for endogenous erythroid colony in the patients with polycythemia vera
      and its clinical significance].
AB  - OBJECTIVE: To investigate the growth of endogenous erythroid colony (EEC) in
      polycythemia vera (PV) patients and its clinical significance. METHODS: Bone
      marrow mononuclear cells of 26 PV patients, 2 secondary erythrocytosis (SE) and
      19 normal controls were cultured by Marsh's method for EEC. RESULTS: 1. EEC was
      present in 25/26 (96.2%) PV patients and was not found in 2 SE patients and 19
      normal controls. 2. The number of EEC and the ratio of EEC/Epo-dependent CFU-E
      (EEC ratio) were positively correlated with the hemoglobin (Hb) levels (r =
      0.608, P = 0.01) in PV patients, but did not correlate with white blood cell
      (WBC) counts, platelet counts and neutrophil alkaline phosphatase scores. 3. EEC
      did not correlate with PV patients' serum Epo levels (r = 0.518, P = 0.125). 4.
      Fifteen PV patients were treated with hydroxyurea and/or interferon-alpha. Their
      EEC ratio before treatment was correlated positively with the time required for
      complete remission (CR) (r = 0.651, P = 0.009) and negatively with the time
      before relapsing (r = -0.529, P < 0.02). 5. EECs of 7 PV patients treated with
      HU/IFN were decreased after their blood cell counts normalization. 6. There was a
      positive correlation between the EEC ratio and the attacks of vascular thrombosis
      (r = 0.524, P = 0.01). (7) The apoptosis of bone marrow mononuclear cells of PV
      patients was less than that of normal controls. PV patients' EEC was negatively
      correlated with the apoptosis of their bone marrow mononuclear cells (r = -0.192,
      P < 0.045). CONCLUSION: EEC is peculiarly present in PV patients, and is a
      sensitive parameter in reflecting the abnormal hematopoietic clone burden and in
      diagnosing and monitoring the disease.

PMID- 14720439
TI  - [Analysis of caspases activity of hematopoietic progenitor cells and its
      significance in myelodysplastic syndromes].
AB  - OBJECTIVE: To investigate the changes of apoptosis and the activity of caspases 3
      and 9 in bone marrow hematopoietic progenitor cells in myelodysplastic syndromes
      (MDS). METHODS: Bone marrow hematopoietic progenitor cells (including both
      CD(34)(+) and CD(34)(-) cells) were collected by negative selection in 34
      patients with MDS. Apoptosis was measured with Annexin V assay and activities of
      caspases 3 and 9 by spectrophotometer. RESULTS: 1. Apoptosis was significantly
      increased in MDS-RA (39.5%, P < 0.01) and MDS-RAEB (31.0%, P < 0.05), but was not
      different statistically in MDS-RAEBt/AML (18.8%) compared with that of control.
      2. Activities of caspases 3 and 9 increased 45 and 20 fold in MDS-RA, increased
      14 and 2 fold in MDS-RAEB, respectively and was not increased in MDS-RAEBt/AML
      compared with that of control. 3. Apoptosis and activities of caspases 3 and 9
      reduced in 3 cases of MDS-RAEB group who progressed into AML. CONCLUSION:
      Increased activities of caspases 3 and 9 may be one of causes of excessive
      apoptosis in MDS. With progress to AML, activities of caspases 3 and 9 and
      apoptosis reduced. Reduced activity of caspase 9 may result in apoptosis "escape"
      and progression into AML.

PMID- 14720440
TI  - [Diagnosis and differential diagnosis of granulocytic sarcomas].
AB  - OBJECTIVE: To investigate the diagnosis and differential diagnosis of
      granulocytic sarcoma (GS). METHODS: The morphological and immunological
      characteristics of 12 cases of GS were studied. FAB classification was made by
      peripheral blood, bone marrow picture and bone marrow biopsy assay. RESULTS: All
      of the 12 cases presented with lymphadenopathy and soft tissue mass.
      Histologically, the tissue infiltration of GS was composed of blastic cells with
      round to oval nuclei showing an even, pale chromatin pattern. Some with cleaved
      or notched nuclei. There were prominent nucleoli and scant cytoplasm in the cells
      and mitosis was easily found. Immunohistochemically, CD(45) and lysozyme were
      positive in all of the cases, MPO in 11 (92%), CD(68) in 10 (83%), CD(34) in 5
      (42%), and TdT in 2 cases (17%). CD(15) and Mac387 were mainly expressed in
      mature granulocytes. Examination of bone marrow sections and marrow aspirate
      smears showed that out of the 11 cases tested 8 were AML-M(2), 2 AML-M(1) and 1
      AML-M(0). Only 1 case was nonleukemic, ie. solitary granulocytic sarcoma.
      CONCLUSION: Granulocytic sarcomas are difficult to identify in routine paraffin
      embedded tissue sections and usually misdiagnosed as non-Hodgkin's lymphomas.
      Immunohistochemistry study with a panel of antibodies in combination with bone
      marrow and peripheral blood examination are helpful in identification of
      granulocytic sarcoma.

PMID- 14720441
TI  - [Effect of agonist anti-CD40 mAb 5C11 on the induction and biological
      characteristics of leukemic dendritic cells].
AB  - OBJECTIVE: To study the impact of an agonist anti-CD(40) monoclonal antibody 5C11
      on the induction and biological characteristics of leukemic dendritic cells.
      METHODS: Combinations of 5C11 and different cytokines were used to induce
      differentiation of leukemic blasts into dendritic cells. Morphology was observed
      by light microscopy. Surface antigens of the induced cells were analyzed by
      fluorescence-activated cell sorting (FACS), the yields of dendritic cell by cell
      counting, the levels of IL-6 and IL-12 by ELISA, T cell proliferating activity by
      allo-mixed lymphocyte reaction (MLR) in vitro. Allogeneic T cells were stimulated
      with leukemic dendritic cells and T-cell cytotoxicity was measured by MTT assay.
      RESULTS: When cultured with combinations of 5C11 and different cytokines, the
      leukemic cells isolated from the patients could differentiate into dendritic
      cells. The morphology showed typical features of dendritic cells, which expressed
      high levels of CD(40), CD(80) and CD(86). In comparison with the original
      leukemia cells, the leukemic dendritic cells secreted less IL-6 but more IL-12 (P
      < 0.05). The leukemic dendritic cells were potent to stimulate the proliferation
      of allogeneic T cells, and the latter was able to lyse the original leukemia
      cells. CONCLUSION: Leukemic blasts could be induced to differentiate into
      functional dendritic cells. It may be of great value in the adoptive immunologic
      therapy of leukemia.

PMID- 14720442
TI  - [The experimental study on inducing and expanding T/NK cells from mononuclear
      cells of human umbilical cord blood].
AB  - OBJECTIVE: To explore the most efficient culture system which can induce cord
      blood (CB)-mononuclear cells (MNC) to differentiate into mature T/NK cells in
      vitro. METHODS: The CB MNCs were cultured in six culture systems respectively for
      4 weeks. The T/NK cell surface phenotypes were analyzed by flow cytometry and the
      absolute numbers of nucleated cells (NCs) were counted at each time point.
      Moreover, cell morphology was identified by Giemsa-Wright staining, and
      cytotoxicity of the cultured cells to K562 and Raji tumor cells was also
      evaluated by MTT method. RESULTS: Cultured in the cytokine cocktail of SCF + FLT
      3L + IL-7 + IL-15 + TNF-alpha + IL-2, the NCs were (20 approximately 26) x
      10(6)/ml in numbers at day 22. The percentage of lymphocytes in the NCs and that
      of CD(3)(+) T cells in the lymphocytes both exceeded 90% at the same time. Most
      of the CD(3)(+) T cells were CD(3)(+)CD(8)(+) and the percentage of
      CD(3)(+)CD(4)(+) T cells declined gradually. The percentage of CD(3)(+)CD(56)(+)
      NKT cells and gamma delta(+)T cells in the lymphocytes arised from lower than 2%
      to 30% approximately 40% and 10% approximately 15%, respectively. CD(3)(
      )CD(56)(+) NK cells were not expanded. The cytotoxic activity of the cultured
      cells to K562 and Raji cells at an effector:target (E:T) ratio of 50:1 was over
      75% and about 32% approximately 65%, respectively. CONCLUSION: The most efficient
      culture system which can induce CB MNC to differentiate into mature T/NK cells in
      vitro is the cytokines cocktail of SCF + FLT-3L + IL-7 + IL-15 + TNF-alpha + IL
      2, and the optimum culture time is 22 days.

PMID- 14720443
TI  - [Synergism of As2S2 and STI 571 in inducing apoptosis of K562 cells].
AB  - OBJECTIVE: To investigate the synergistic effect of As(2)S(2) and STI 571 on K562
      cells and its mechanism. METHODS: The inhibitive effect of As(2)S(2) on the
      proliferation of K562 cells was determined by cell number count. Cell apoptosis
      was assessed by flow cytometry, DNA fragmentation and morphology. Protein
      expression was determined by Western-blot and gene expression by RT-PCR. RESULTS:
      As(2)S(2) could significantly inhibit the proliferation and induce apoptosis of
      K562 cells in a dose and time-dependent manner at concentrations from 1
      micromol/L to 5 micromol/L for 24 approximately 72 h. 34.4%, 21.8% and 46.0% of
      the treated-cells displayed apoptosis at 3 micro mol/L for 72 h, 5 micromol/L for
      48 h and 5 micromol/L for 72 h, respectively. Compared to treatment with STI571
      (0.25 approximately 1.00 micromol/L) or As(2)S(2) (1 approximately 5 micromol/L)
      alone, treatment of K562 cells with As(2)S(2) and STI571 combination induced more
      cell apoptosis. (18.4 +/- 1.4)% and (15.8 +/- 1.2)% cells underwent apoptosis at
      1 micromol/L STI571 for 48 h and 5 micromol/L As(2)S(2) for 48 h, respectively,
      and (40.6 +/- 2.0)% cells did in combination treatment (P < 0.05). For U937
      cells, the percentages of apoptotic cells were (6.0 +/- 1.1)% at 1 micromol/L
      STI571 for 48 h, (4.5 +/- 1.2)% at 5 micromol/L As(2)S(2) for 48 h, and (7.3 +/-
      1.0)% in combination treatment. As(2)S(2) decreased the bcr-abl fusion protein
      expression and PTK activity of c-abl and bcr-abl, but not for bcr-abl expression.
      CONCLUSION: Combination treatment with As(2)S(2) and STI 571 induced more
      apoptosis of K562 cells. The reduction of PTK activity may be involved in the
      mechanisms.

PMID- 14720444
TI  - [Study of ex vivo expansion of mouse hematopoietic stem/progenitor cells and the
      use of them for hematopoiesis reconstitution].
AB  - OBJECTIVE: To explore the rapid neutrophil engraftment and long-term
      hematopoietic reconstitution. METHODS: Mononuclear cells (MNCs) were isolated
      from 5-Fu treated male BDF1 mouse bone marrow and CD(34)(+)/c-kit(+) cells were
      selected from the MNCs by using MoFlo Cell Sorter. MNCs and CD(34)(+)/c-kit(+)
      cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells
      (MSCs) in a two-step expansion. The expanded cells were then transplanted into
      sublethally irradiated female BDF1 mice. RESULTS: Co-culture with MSCs resulted
      in 10.8-, 4.8-, 65.9- and 38.8-fold increases yields of median total nucleated
      cells, CD(34)(+) cells, GM-CFC and HPP-CFC, respectively, as for the MNCs
      culture, and 76.1-, 2.9-, 71.7- and 51.8-fold increase respectively for the
      CD(34)(+)/c-kit(+) cell culture. The expanded cells could rapidly engraft in the
      sublethally, irradiated mice, reconstitute their hematopoiesis, and be detected
      in the recipients bone marrow 2 months after transplantation. CONCLUSIONS:
      Hematopoietic stem/progenitor cells co-cultures with MSCs in two-step expansion
      could increase expansion yields of total nucleated cells, GM-CFC and HPP-CFC. The
      availability of increased numbers of expanded cells may result in more rapid
      engraftment of neutrophils following infusion to transplant recipients.

PMID- 14720445
TI  - [Effect of Tpo and/or IL-11 gene modified stromal cells on the expansion of CD34+
      CD38- hematopoietic primitive progenitor cells].
AB  - OBJECTIVE: To investigate the effects of Tpo and/or IL-11 gene modified stromal
      cells on the expansion of CD(34)(+) hematopoietic stem/progenitor cells in cord
      blood. METHODS: Retroviral vectors containing Tpo or IL-11 gene were constructed
      and used to transfect the stromal cell line HFCL. Tpo and/or IL-11 mRNA was
      assayed by Northern blot. Non-modified stromal cells were used, CD(34)(+)
      hematopoietic stem/progenitor cells from cord blood were expanded on gene
      modified stromal cells for 7 days. The phenotype of CD(34)(+)CD(38)(-) primitive
      progenitors was detected by flow cytometry. RESULTS: HFCL expressed Tpo and/or IL
      11 mRNA after transfected by the retroviral vectors. The percentages of
      CD(34)(+)CD(38)(-) primitive progenitors in the cultures of Tpo, IL-11 and Tpo +
      IL-11 modified HFCL were (1.8 +/- 0.24)%, (1.62 +/- 0.23)%, and (2.45 +/- 0.28)%,
      respectively, which were higher than that in the control [(0.8 +/- 0.23)%].
      CONCLUSION: The stromal cells modified by Tpo and/or IL-11 gene were able to
      enhance ex vivo expansion of CD(34)(+) and CD(34)(+)CD(38)(-) hematopoietic
      stem/progenitor cells from cord blood.

PMID- 14720446
TI  - [Synergistic effect of Apo2L and chemotherapeutic agents on leukemia cells].
AB  - OBJECTIVE: To explore if the antileukemic drugs Vp16 or Ara-C are able to
      upregulate DR5 gene expression and enhance Apo2L-induced apoptosis of HL-60
      cells. METHODS: Cell apoptosis was determined by flow cytometry after annexin
      V/PI staining, the effect of Apo2L on fresh leukemia cells by MTT reduction
      assay, the expression of DR5 gene in HL-60 cells by semi-quantitative RT-PCR.
      RESULTS: 1. Apo2L induced apoptosis of HL-60 cells in a dose-dependent manner. 2.
      Apo2L inhibited the proliferation of fresh leukemia cells, but there was
      difference among different subtypes. 3. Vp16 or Ara-C upregulated DR5 gene
      expression and augmented Apo2L-induced apoptosis in HL-60 cells. CONCLUSION:
      Apo2L could induce apoptosis of HL-60 cells and inhibit the proliferation of
      fresh leukemia cells. Ara-C or Vp16 upregulated DR5 gene expression and increased
      the sensitivity of HL-60 to Apo2L-induced cytotoxicity. Apo2L might be a
      promising antileukemic agent for the treatment of leukemia.

PMID- 14720447
TI  - Treatment of nonalcoholic steatohepatitis.

PMID- 14720448
TI  - Pruritus in chronic liver disease: mechanisms and treatment.
AB  - Pruritus is a complication of liver disease. It can have a marked negative impact
      on quality of life; when intractable, it is an indication for liver
      transplantation. The cause of this type of pruritus is unknown. There is,
      however, evidence to suggest that the pruritus associated with liver disease is
      mediated, at least in part, by endogenous opioids. A central mechanism has been
      proposed. Therapeutic interventions have concentrated on the removal of presumed
      and unknown pruritogens from the circulation, hepatic enzyme induction, and, over
      the past decade, opiate antagonists, the first specific treatment for the
      pruritus of cholestasis. Other pharmacologic interventions that change
      neurotransmission have recently been reported to decrease the pruritus in
      patients with liver disease, as has a newly developed system that applies albumin
      based dialysis. These interventions are promising, but they must be tested in
      properly controlled behavioral trials.

PMID- 14720449
TI  - Guidelines for stopping therapy in chronic hepatitis C.
AB  - Tremendous progress has been made in the treatment of chronic hepatitis C. Over
      50% of patients treated with pegylated interferon and ribavirin experience
      permanent eradication of the hepatitis C virus. The indications for therapy have
      been expanded based on evolving data concerning the safety and efficacy of these
      agents. Although awareness of which patients in whom to initiate therapy is
      important, a thorough understanding of features of the antiviral response is also
      necessary so that treatment can be discontinued when the chances of sustained
      response are nil. Recent studies have defined virologic milestones that are
      useful for managing patients during antiviral therapy. Pretreatment genotype and
      response to therapy measured at weeks 12 and 24 of treatment have been identified
      as key determinants in decisions about continuing treatment. Progress in defining
      early treatment stopping points has reduced adverse events in patients who are
      unlikely to respond to therapy.

PMID- 14720450
TI  - Fat, diabetes, and liver injury in chronic hepatitis C.
AB  - It is increasingly recognized that host factors can modulate the fibrogenic
      response in patients with chronic hepatitis C. Obesity, because of its
      prevalence, and diabetes, which seems to occur more frequently in patients
      infected by the hepatitis C virus (HCV), are often present in patients with
      chronic hepatitis C. Both conditions result in fatty liver, which in turn is
      associated with more severe liver damage, especially fibrosis or inflammation.
      Steatosis can either originate from associated metabolic alterations (insulin
      resistance resulting in metabolic steatosis) or from a direct cytopathic effect
      of the virus (genotype 3, resulting in viral steatosis). Metabolic steatosis
      seems to be a factor in resistance to antiviral therapy, whereas viral steatosis
      is reduced in sustained responders. Whether metabolic steatosis has a direct role
      in liver fibrosis progression or is only a surrogate marker of an underlying
      defect triggering fibrogenesis, such as insulin resistance, is a subject of
      debate. High serum glucose levels and diabetes have a strong and independent
      profibrogenic impact. Exciting new data are expanding our understanding of the
      mechanisms of steatogenesis in HCV infection and providing potential links
      between insulin resistance or hyperglycemic states and liver fibrogenesis.

PMID- 14720451
TI  - Controversies in liver biopsy: who, where, when, how, why?
AB  - Liver biopsy continues to have a central role in the evaluation of patients with
      suspected liver disease. The procedure is often indicated to evaluate otherwise
      unexplained liver biochemical test abnormalities, but the precise degree of serum
      aminotransferase elevations that should prompt a liver biopsy is controversial,
      as is the need for liver biopsy in all patients with suspected nonalcoholic fatty
      liver disease and chronic hepatitis C. Standard liver biopsy is contraindicated
      in patients with severe coagulopathy and ascites, although the degree of
      coagulopathy that contraindicates a liver biopsy is controversial. A transjugular
      approach is an alternative in patients with coagulopathy or ascites. Controversy
      surrounds all the technical aspects of liver biopsy, particularly the choice of
      needle (cutting vs suction) and the use of ultrasound to mark or guide the biopsy
      site. Bleeding is the major complication of liver biopsy, with a risk of 0.3%;
      cutting needles are more likely to cause hemorrhage than are suction needles.
      Traditionally, liver biopsy has been the province of the hepatologist/
      gastroenterologist. However, an increasing number of liver biopsies are performed
      by radiologists. The implications of this trend with respect to patient outcome,
      safety, and training of fellows is unclear.

PMID- 14720452
TI  - Hepatocellular carcinoma: updates in primary prevention.
AB  - Hepatocellular carcinoma is a significant cause of mortality worldwide and a
      growing problem in the United States. Treatment options are often limited, and
      median survival is less than 1 year. Thus, prevention may provide the best
      opportunity to alter the natural history of this disease. Primary prevention is
      best exemplified by the successes of such public health measures as universal
      hepatitis B vaccination. Such antiviral therapies as interferon may also have a
      role. Lessons can be learned from complementary and alternative medicine.
      Nevertheless, more work is needed in understanding hepatocarcinogenesis and in
      developing models to assess potential chemopreventive agents.

PMID- 14720453
TI  - Screening for hemochromatosis: patients with liver disease, families, and
      populations.
AB  - Hereditary hemochromatosis is a common autosomal- recessive disorder of iron
      overload usually occurring in individuals who are homozygous for a C282Y mutation
      in the hemochromatosis (HFE) gene. Current screening methods can detect affected
      individuals early in disease pathogenesis, enabling early institution of
      effective treatment that can restore normal life expectancy. Phenotypic screening
      of adults using transferrin saturation and serum ferritin levels identifies the
      majority of individuals who develop iron overload. HFE genotyping, when combined
      with serum biochemical measurements, has reduced reliance on liver biopsy as a
      diagnostic tool and is the preferred initial screening modality for families with
      an affected individual. Genetic testing has altered previously held views
      regarding the high level of penetrance of the disease. Although the majority of
      C282Y homozygotes develop increased body iron stores, end-organ damage occurs
      much less frequently than previously thought. Screening is recommended in high
      risk groups and in those with a high index of clinical suspicion. Opportunistic
      screening during routine health assessments may also be recommended. However,
      large-scale screening of the average-risk population is not recommended on the
      basis of current evidence.

PMID- 14720454
TI  - Diagnosis and treatment of cholangiocarcinoma.
AB  - Epidemiologic studies have demonstrated increasing mortality rates from
      intrahepatic cholangiocarcinoma during the past decades. Primary sclerosing
      cholangitis is the most important predisposing condition to the development of
      cholangiocarcinoma. Improvements in noninvasive diagnostic techniques have led to
      decreased use of invasive procedures. Magnetic resonance imaging (MRI) has the
      potential to depict parenchymal, ductal, and vascular tumor involvement. However,
      diagnosis can be difficult, and often ultrasonography, MRI, CT, and invasive
      cholangiography are complementary investigations. Genetic aberrations in brush
      cytology specimens should be explored further in prospective studies. Endoscopic
      ultrasonography, intraductal ultrasonography, and positron emission tomography
      are interesting techniques that are under evaluation. Radical surgery with
      negative histologic margins is the only curative option in cholangiocarcinoma.
      With more aggressive surgical approaches, including partial hepatectomy, 3-year
      survival rates of 35% to 50% can be achieved. Liver transplantation for
      unresectable cholangiocarcinoma was shown to be feasible in pilot studies of
      highly selected patients.

PMID- 14720456
TI  - Chronic hepatitis C in African Americans and other minority groups.
AB  - Chronic hepatitis C virus (HCV) is the most common bloodborne infection in the
      United States. An estimated 2.7 million Americans are infected, with the greatest
      prevalence of infection in African Americans at 3.2%. African Americans account
      for 22% of Americans with HCV. Recent studies have shown that African Americans
      are less likely to have cirrhosis than similarly infected non-Hispanic white
      patients and are more likely to have genotype 1 infection and to develop
      hepatocellular carcinoma. Several studies have shown that the response rates of
      African Americans to interferon and ribavirin are significantly lower than those
      for non-Hispanic whites. Despite the relatively low percentage of African
      American patients in these early studies, similar preliminary results are being
      found in larger prospective studies with the newer treatment regimens of
      pegylated interferon and ribavirin. Differences in immunologic status, viral
      kinetics, and iron studies have also been found in HCV-infected African-American
      patients. Less is known about Mexican Americans and other minority groups because
      they are poorly represented in clinical trials. Efforts at increasing racial
      diversity in clinical trials are ongoing.

PMID- 14720455
TI  - New concepts of the pathogenesis of alcoholic liver disease lead to novel
      treatments.
AB  - Activation of methionine to S-adenosylmethionine is depressed in alcoholics. Its
      repletion opposes alcoholic liver cirrhosis in baboons, decreases mortality in
      cirrhotic patients, and opposes oxidative stress resulting from cytochrome
      P4502E1 (CYP2E1) induction by alcohol, ketones, and fatty acids. Their excess
      causes alcoholic and nonalcoholic steatohepatitis. CYP2E1 is also induced in
      Kupffer cells, promoting their activation and release of inflammatory cytokines,
      including tumor necrosis factor (TNF)-alpha. The TNF-alpha inhibitor
      pentoxifylline decreased mortality from alcoholic hepatitis.
      Polyenylphosphatidylcholine (PPC), an antioxidant phosphatidylcholine mixture
      extracted from soybeans, 50% of which consists of the highly bioavailable
      dilinoleoylphosphatidylcholine, restores phospholipids of the damaged membranes
      and reactivates their enzymes, including phosphatidylethanolamine
      methyltransferase, needed for phospholipid regeneration. In baboons, PPC
      prevented cirrhosis by stimulating collagenase and by opposing lipid
      peroxidation, which produces the fibrogenic hydroxynonenal. PPC was beneficial in
      patients with alcoholic hepatitis, and it opposed fibrosis in heavy drinkers and
      decreased aminotransferases in patients with hepatitis C. The antioxidant
      silymarin also successfully opposed alcoholic cirrhosis in baboons and in some
      but not all clinical trials; this effect also pertains to a-tocopherol. The anti
      inflammatory corticosteroids and colchicine yielded mixed results. Finally,
      replacing long-chain with medium-chain triglycerides opposed the fatty liver
      experimentally and clinically.

PMID- 14720457
TI  - Advances in alcoholic liver disease.
AB  - Cytokines are mediators of cellular communication produced by multiple liver cell
      types. Cytokines can directly induce either necrosis or apoptosis. They can also
      recruit such cells as neutrophils and lymphocytes, which can mediate liver
      damage. Increased levels of hepatotoxic cytokines such as tumor necrosis factor
      alpha are documented in alcoholic liver disease (ALD) and nonalcoholic
      steatohepatitis (NASH) and have been shown to play a mechanistic role in both of
      these disease processes. Transforming growth factor-beta is a profibrotic
      cytokine that is critical in hepatic fibrosis. Beneficial cytokines, such as
      interleukin (IL)-10 and -6, also exist. Such beneficial cytokines as adiponectin
      are made outside the liver and appear to protect against ALD and NASH. This
      article reviews the relevance of cytokines in human and experimental forms of
      liver injury, focusing on modulation of cytokines and the use of beneficial
      cytokines in treatment and prevention of liver injury in ALD, NASH, and hepatitis
      C.

PMID- 14720458
TI  - New therapies for chronic hepatitis C virus infection.
AB  - Chronic hepatitis C infection is associated with significant morbidity and
      mortality in addition to substantial social and health-related costs. Since the
      identification of the virus and determination of the HCV genome over a decade
      ago, considerable progress has been made in the treatment of chronic hepatitis C
      infection. However, the current standard combination of interferon-based
      therapies and ribavirin is effective in only 50% of patients. In addition, this
      combination is expensive, requires lengthy periods of administration, and is
      associated with significant side effects. Furthermore, no effective preventive
      measure, such as vaccination, is currently available. A number of newer
      therapies, including protease and helicase inhibitors, ribozymes, antisense
      therapies, and therapeutic vaccines, are in preclinical and clinical development
      and may significantly enhance existing therapeutic options for the future.

PMID- 14720459
TI  - Integrative molecular and developmental biology of adult stem cells.
AB  - Stem cells are believed to be important for regeneration of several adult
      tissues. Recently, adult stem cells with very broad differentiation potential
      have been identified although whether they represent vestigial primitive
      pluripotent stem cells or products of extremely rare de-differentiation events
      involving tissue-specific stem cells is not known. Transdifferentiation of tissue
      specific stem cells across lineage boundaries has also been demonstrated but the
      relative inefficiency of the process in vivo, even in the presence of tissue
      damage, questions whether such a mechanism is of physiologic relevance.
      Interestingly, among adult stem cells, the capacity for lineage switching appears
      to be greatest in stem cells that can be cultured ex vivo for extended periods.
      If the normal cell fate decisions of diverse adult stem cell types could be
      reliably redirected at high frequency in situ, possible regenerative therapies
      for a wide variety of diseases could be envisioned. An integrated understanding
      of the transcriptional regulatory networks that comprise the various adult stem
      cell entities as well as the signaling pathways governing their differentiation
      into therapeutically useful cell types will facilitate clinical application of
      these exciting findings.

PMID- 14720460
TI  - The lateral line of zebrafish: a model system for the analysis of morphogenesis
      and neural development in vertebrates.
AB  - The lateral line of the zebrafish has many of the advantages that made the
      sensory organs of Drosophila a very productive model system: 1) it comprises a
      set of discrete sense organs (neuromasts) arranged in a defined, species-specific
      pattern, such that each organ can be individually recognized; 2) the neuromasts
      are superficial and easy to visualize, and the innervating neurons are easy to
      label; 3) the sensory projection is simple yet reproducibly organized. Here we
      describe some of the tools that can be used to investigate the development of
      this system, and we illustrate their usefulness with specific examples. We
      conclude that the lateral line is uniquely suited among vertebrate sensory
      systems for a molecular, cellular and genetic analysis of pattern formation and
      of neural development.

PMID- 14720461
TI  - The spatial restrictions of 5'HoxC genes expression are maintained in adult newt
      spinal cord.
AB  - Urodele amphibians are the only adult vertebrates possessing the capacity to
      regenerate their limbs and tail after amputation. Epimorphic regeneration is
      characterized by the accumulation of undifferentiated and dividing mesenchymal
      cells originating from the tissues of the stump, which form a blastema. It has
      been proposed that the ability to regenerate precisely the amputated structures
      depends on a 'positional memory' of the cells at the level of amputation plane
      and that a continuum of positional value would be present in adult urodeles along
      the appendages able to regenerate. Hox genes are good candidates for playing a
      role in providing the capacity for regeneration and for carrying positional
      information. Here, we report the cloning of four AbdB-like genes (Hoxa9, Hoxc10,
      Hoxc12 and Hoxc13) in the newt Pleurodeles waltl (Pw). To analyse their
      expression pattern along the antero-posterior (AP) axis of adult urodele central
      nervous system (CNS), we used the reverse transcription-polymerase chain reaction
      (RT-PCR) and showed that the 5'HoxC genes expression pattern conforms to the
      usual spatial colinearity rule. In addition, the expression level in tail
      regenerates of PwHoxc13, PwHoxc12, and PwHoxc10 was respectively 20, 7 and 2 fold
      higher than in adult tail. These last results suggest that 5'HoxC genes could
      specify positional memory in adult spinal cord (SC) and could be involved in
      axial patterning of the tail during regeneration.

PMID- 14720462
TI  - The Drosophila kinesin-I associated protein YETI binds both kinesin subunits.
AB  - The microtubule-based motor kinesin-I is essential for the intracellular
      transport of membrane-bound organelles in the Drosophila nervous system and
      female germ line. A number of studies have demonstrated that kinesin-I binds to
      its intracellular cargos through protein-protein interactions between the kinesin
      tail domain and proteins on the cargo surface. To identify proteins that mediate
      or regulate kinesin-cargo interactions, we have performed yeast two-hybrid
      screens of a Drosophila embryonic cDNA library, using the tetratricopeptide
      repeats of the kinesin light chain and amino acids 675-975 of the kinesin heavy
      chain as baits. One of the proteins we have identified is YETI. Interestingly,
      YETI has the unique ability to bind specifically to both subunits of the kinesin
      tail domain. An epitope-tagged YETI fusion protein, when expressed in Drosophila
      S2 cultured cells, binds to kinesin-I in copurification assays, suggesting that
      YETI-kinesin-I interactions are context-independent. Immunostaining of cultured
      cells expressing YETI shows that YETI accumulates in the nucleus and cytosol.
      YETI is evolutionarily conserved, and its yeast homolog (AOR1) may have a role in
      regulating cytoskeletal dynamics or intracellular transport. Collectively, these
      results demonstrate that YETI interacts with both kinesin subunits of the kinesin
      tail domain, and is potentially involved in kinesin-dependent transport pathways.

PMID- 14720463
TI  - Tyrosine kinase-mediated cell signalling in the activation of Mytilus hemocytes:
      possible role of STAT-like proteins.
AB  - In bivalve molluscs, cell-mediated immunity is carried out by circulating
      hemocytes, resembling the monocyte/macrophage lineage of vertebrates, that can
      kill the microbes through phagocytosis and various cytotoxic reactions. Previous
      data demonstrated that activation of MAPKs (Mitogen Activated Protein Kinases) is
      involved in the response of mussel hemocytes (Mytilus galloprovincialis Lam.) to
      bacterial challenge. In this work, the possibility that modulation of components
      of tyrosine kinase-mediated cell signalling may participate in the activation of
      mussel hemocytes was investigated. Cell pre-treatment with the macrophage
      activator IFN gamma significantly increased the bactericidal activity of mussel
      hemocytes towards E. coli. Human recombinant IFN gamma stimulated tyrosine
      phosphorylation of different members of STAT-like proteins (Signal Transducers
      and Activators of Transcription), as evaluated by Western blotting of hemocyte
      protein extracts with specific anti-phospho-STAT antibodies. A similar increase
      in phosphorylation of immunoreactive STATs was observed in hemocytes incubated
      with E. coli, this indicating that tyrosine phosphorylation of STAT-like members
      represents a physiological step in hemocyte activation. IFN gamma lead to
      persistent phosphorylation of immunoreactive STAT1, a transcription factor that
      plays a critical role in innate immunity towards Gram negative bacteria in
      mammalian systems; moreover, hemocyte pretreatment with IFN gamma significantly
      increased bacteria-induced STAT1 phosphorylation, whereas IFN alpha did not. IFN
      gamma also transiently affected the phosphorylation state of different MAPKs. The
      extent and time course of MAPK phosphorylation induced by IFN gamma were distinct
      from those elicited by either IFN alpha or bacterial challenge. Overall, the
      results indicate that the hemocyte function can be modulated by heterologous
      cytokines and bacterial signals that act in concert through tyrosine kinase
      mediated transduction pathways converging on STAT- and MAPK-like members.

PMID- 14720464
TI  - Myoblast migration is prevented by a calpain-dependent accumulation of MARCKS.
AB  - Calpains, also called calcium activated neutral cysteine proteases are presently
      known to play pivotal roles in physiological and biological phenomena such as
      signal transduction, cell spreading and motility, apoptosis, regulation of cell
      cycle and regulation of muscle cell differentiation. Concerning this last point,
      calpains have been shown to play a crucial role during the earlier myogenesis. In
      this study we have analyzed the involvement of calpains during an important step
      of myogenesis: myoblast migration. Our findings show that myoblast migration was
      drastically reduced when the expression of micro- and m-calpain was decreased. We
      have also observed that MARCKS (myristoylated alanine rich C kinase substrate), a
      protein localized at focal adhesion sites, was significantly accumulated when the
      expression levels of calpains were decreased. Also, using phorbol myristate
      acetate, (an activator of PKC) and plasmids carrying the full-length cDNA of
      MARCKS or a cDNA fragment lacking the phosphorylation site domain, we
      demonstrated that normal myoblast migration is dependent on MARCKS
      phosphorylation and localization.

PMID- 14720465
TI  - Different regulation of the Trio Dbl-Homology domains by their associated PH
      domains.
AB  - Guanine nucleotide exchange factors for Rho-GTPases (Rho-GEFs) invariably share a
      catalytic Dbl-Homology (DH) domain associated with a Pleckstrin Homology (PH)
      domain, whose function in Rho-GEF activation is not well understood. Trio is the
      first member of an emerging family of Dbl proteins containing two Rho-GEF domains
      (GEFD1 and GEFD2). TrioGEFD1 activates the GTPases RhoG and Rac1, while TrioGEFD2
      acts on RhoA. In this study, we have investigated the roles of the two PH domains
      of Trio in Rho-GEF activity. We show that TrioPH1 is required for GEFD1-mediated
      induction of actin cytoskeleton remodeling and JNK activation. TrioPH1 is
      involved both in the catalytic activity and in the subcellular localization of
      its associated DH domain, by acting as a cytoskeletal targeting signal. Moreover,
      TrioPH1 in association with DH2 activates the JNK pathway, by an unknown
      mechanism independent of DH2 catalytic activity. TrioPH2 does not behave as a
      targeting module in intact cells. TrioPH2 inhibits DH2-dependent stress fiber
      formation, which correlates with the TrioPH2-mediated inhibition of DH2 GEF
      activity. In addition, expression in the neuron-like PC12 cell line of the intact
      Trio protein deleted of each PH domain shows that only TrioPH1 is required for
      Trio-induced neurite outgrowth. Taken together, these data demonstrate that the
      two PH domains play a different role in the control of Trio Rho-GEF function.

PMID- 14720466
TI  - Alteration of poly(ADP-ribose) glycohydrolase nucleocytoplasmic shuttling
      characteristics upon cleavage by apoptotic proteases.
AB  - Poly(ADP-ribosyl)ation is an important post-translational modification which
      mostly affects nuclear proteins. The major roles of poly(ADP-ribose) synthesis
      are assigned to DNA damage signalling during base excision repair, apoptosis and
      excitotoxicity. The transient nature and modulation of poly(ADP-ribose) levels
      depend mainly on the activity of poly(ADP-ribose) polymerase-1 (PARP-1) and
      poly(ADP-ribose) glycohydrolase (PARG), the key catabolic enzyme of poly(ADP
      ribose). Given the fact that PARG substrate, poly(ADP-ribose), is found almost
      exclusively in the nucleus and that PARG is mainly localized in the cytoplasm, we
      wanted to have a closer look at PARG subcellular localization in order to better
      understand the mechanism by which PARG regulates intracellular poly(ADP-ribose)
      levels. We examined the subcellular distribution of PARG and of its two
      enzymatically active C-terminal apoptotic fragments both biochemically and by
      fluorescence microscopy. Green fluorescent protein (GFP) fusion proteins were
      constructed for PARG (GFP-PARG), its 74 kDa (GFP-74) and 85 kDa (GFP-85)
      apoptotic fragments and transiently expressed in COS-7 cells. Localization
      experiments reveal that all three fusion proteins localize predominantly to the
      cytoplasm and that a fraction also co-localizes with the Golgi marker FTCD.
      Moreover, leptomycin B, a drug that specifically inhibits nuclear export signal
      (NES)-dependent nuclear export, induces a redistribution of GFP-PARG from the
      cytoplasm to the nucleus and this nuclear accumulation is even more pronounced
      for the GFP-74 and GFP-85 apoptotic fragments. This observation confirms our
      hypothesis for the presence of important regions in the PARG sequence that would
      allow the protein to engage in CRM1-dependent nuclear export. Moreover, the
      altered nuclear import kinetics found for the apoptotic fragments highlights the
      importance of PARG N-terminal sequence in modulating PARG nucleocytoplasmic
      trafficking properties.

PMID- 14720467
TI  - The role of innate immune responses in the heart in health and disease.
AB  - The ability of the myocardium to successfully adapt to environmental stress
      ultimately determines whether the heart will decompensate and fail, or whether it
      will maintain preserved function. Despite the importance of the myocardial
      response to environmental stress, very little is known with respect to the
      biochemical mechanisms that are responsible for mediating and integrating the
      stress response in the heart. The present review summarizes recent experimental
      material that suggests that the heart possesses a germ-line encoded "innate"
      stress response that is activated in response to diverse forms of tissue injury.
      The extant literature suggests that this innate stress response plays an
      important role in initiating and integrating homeostatic responses within the
      heart. Nonetheless, as will be discussed further herein, these inflammatory
      mediators all have the potential to produce cardiac decompensation when expressed
      at sufficiently high concentrations.

PMID- 14720468
TI  - Expression of CD36 in macrophages and atherosclerosis: the role of lipid
      regulation of PPARgamma signaling.
AB  - Several macrophage scavenger receptors have been identified that bind and
      internalize modified low-density lipoprotein particles. Although the
      pathophysiologic roles played by these receptors in human disease are still
      unproven, data from murine models of atherosclerosis have demonstrated a
      significant role in atherosclerotic foam cell development and vascular lesion
      development for two receptors: the type A scavenger receptor (SR-A) and the type
      B scavenger receptor, CD36. This review addresses the regulation and potential
      role of CD36 in macrophage foam cell formation and atherosclerosis, with
      particular emphasis on the mechanisms by which CD36 expression is altered in
      response to lipid modulation of peroxisome proliferator-activated receptor gamma
      signaling.

PMID- 14720469
TI  - Molecular regulation of cardiac chamber-specific gene expression.
AB  - This review focuses on recent studies investigating the genetic regulatory
      mechanisms leading to formation of morphologically, functionally, and molecularly
      distinct cardiac chambers. The regulation of four representative chamber-specific
      genes that have been studied in detail is reviewed. These genes include the
      atrial-specific genes, myosin light chain-2a (MLC2a), slow myosin heavy chain-3
      (slow MyHC3), and atrial natriuretic factor (ANF) and the ventricular specific
      gene, myosin light chain-2v (MLC2v). Comparison of these promoters reveals some
      generalizations about the regulatory mechanisms involved in chamber-specific gene
      expression but, equally, indicates the large gaps in the knowledge concerning
      this intriguing genetic program.

PMID- 14720470
TI  - Role of platelets in the development of atherosclerosis.
AB  - Platelets are blood cell fragments that originate from the cytoplasm of
      megakaryocytes in the bone marrow and circulate in blood to play a major role in
      the hemostatic process and in thrombus formation after an endothelial injury.
      Recent studies have provided insight into platelet functions in inflammation and
      atherosclerosis. A range of molecules, present on the platelet surface and/or
      stored in platelet granules, contributes to the cross-talk of platelets with
      other inflammatory cells during the vascular inflammation involved in the
      development and progression of atherosclerosis. This review discusses the nature
      of these molecules and the mechanisms involved in the participation of platelets
      in atherosclerosis, with emphasis on P-selectin, platelet-monocyte interactions,
      chemokines, and inflammatory cytokines.

PMID- 14720471
TI  - Pacemaker channels and sinus node arrhythmia.
AB  - Cardiac pacemaker activity is regulated by at least five different classes of ion
      channels and by the opposing influence of sympathetic and parasympathetic
      stimulation. Inactivation of several genes, including a subunit coding for the
      potassium channel activated by the muscarinic receptor, I(KACh); the calcium
      channel, I(Ca,); and the hyperpolarization-activated channel, I(f), results in
      sinus node arrhythmia. Inactivation of the gene for the hyperpolarization
      activated, cyclic nucleotide-gated channel isoform HCN2 or HCN4 and the use of
      pacemaker channel blockers show that (a) HCN2 prevents the diastolic membrane
      potential from becoming too negative, (b) HCN4 is the major channel mediating
      sympathetic stimulation of the pacemaker activity, and (3) complete blockage of
      the I(f) current is compatible with slow sinus node rhythm.

PMID- 14720472
TI  - Inherited sodium channelopathies: a continuum of channel dysfunction.
AB  - Voltage-gated sodium channels are transmembrane proteins that produce the ionic
      current responsible for the rising phase of the cardiac action potential and play
      a fundamental role in the initiation, propagation, and maintenance of normal
      cardiac rhythm. Inherited mutations in SCN5A, the gene encoding the pore-forming
      subunit of the cardiac Na+ channel, have been associated with distinct cardiac
      rhythm syndromes: the congenital long QT syndrome, Brugada syndrome, and isolated
      conduction disease. Electrophysiologic characterization of heterologously
      expressed mutant Na+ channels have revealed gating defects that, in many cases,
      can explain the distinct phenotype associated with the rhythm disorder. However,
      recent studies have revealed significant overlap between aberrant rhythm
      phenotypes, and single mutations have been identified that evoke multiple rhythm
      disorders with common gating lesions. These new insights enhance understanding of
      the structure-function relationships of voltage-gated Na+ channels, and also
      highlight the complexities involved in linking single mutations, ion-channel
      behavior, and cardiac rhythm.

PMID- 14720473
TI  - Copper uptake by Elsholtzia splendens and Silene vulgaris and assessment of
      copper phytoavailability in contaminated soils.
AB  - Tolerance and metal uptake are two essential characteristics required for
      phytoextraction of metals from contaminated soils. We compared tolerance and Cu
      uptake of Elsholtzia splendens (reported previously to be a Cu hyperaccumulator)
      with Silene vulgaris (the Imsbach population, a well-known Cu-tolerant excluder
      species), using 30 soils varying widely in total Cu concentration (19-8645 mg kg(
      1)). We further investigated the effectiveness of different soil testing methods
      for predicting plant metal uptake. The results showed that both Elsholtzia
      splendens and Silene vulgaris were tolerant to Cu, especially Silene vulgaris.
      However, Elsholtzia splendens did not hyperaccumulate Cu, but behaved as a
      typical Cu excluder like Silene vulgaris. The concentrations of Cu in both plants
      correlated more closely with 1 M NH4NO3 extractable Cu, soil solution Cu, or
      effective Cu concentration determined using DGT, than with soil total Cu, EDTA
      extractable Cu or free Cu2+ activity. The relationships between soil solution
      properties and root Cu concentrations were further investigated using multiple
      regression. The results showed that increasing soil solution pH increased root Cu
      concentration when free Cu2+ activity was held constant, suggesting a higher
      phytoavailability of free Cu2+ at a higher pH. Soil solution DOC appeared to play
      two contrasting roles on the phytoavailability of Cu: (1) reducing Cu
      availability by complexing Cu; and (2) increasing Cu availability at the same
      level of free Cu2+ activity by providing a strong buffer for free Cu2+. The
      results are consistent with the intensity/capacity concept for phytoavailability
      of metals in soils.

PMID- 14720474
TI  - Antioxidative responses to arsenic in the arsenic-hyperaccumulator Chinese brake
      fern (Pteris vittata L.).
AB  - This study measured antioxidative responses of Chinese brake fern (Pteris vittata
      L.) upon exposure to arsenic (As) of different concentrations. Chinese brake fern
      was grown in an artificially-contaminated soil containing 0 to 200 mg As kg(-1)
      (Na2HAsO4) for 12 weeks in a greenhouse. Soil As concentrations at < or =20 mg
      kg(-1) enhanced plant growth, with 12-71% biomass increase compared to the
      control. Such beneficial effects were not observed at >20 mg As kg(-1). Plant As
      concentrations increased with soil As concentrations, with more As being
      accumulated in the fronds (aboveground biomass) than in the roots and with
      maximum frond As concentration being 4675 mg kg(-1). Arsenic uptake by Chinese
      brake enhanced uptake of nutrient elements K, P, Fe, Mn, and Zn except Ca and Mg,
      whose concentrations mostly decreased. The contents of non-enzymatic antioxidants
      (glutathione, acid-soluble thiol) followed similar trends as plant As
      concentrations, increasing with soil As concentrations, with greater contents in
      the fronds than in the roots especially when exposed to high As concentrations
      (>50 mg kg(-1)). The activities of enzymatic antioxidants (superoxide dismutase,
      catalase, ascorbate peroxidase, guaiacol peroxidase) in Chinese brake followed
      the same trends as plant biomass, increasing with soil As up to 20 mg kg(-1) and
      then decreased. The results indicated though both enzymatic and non-enzymatic
      antioxidants played significant roles in As detoxification and hyperaccumulation
      in Chinese brake, the former is more important at low As exposure (< or =20 mg
      kg(-1)), whereas the latter is more critical at high As exposure (50-200 mg kg(
      1)).

PMID- 14720475
TI  - Organochlorine contaminants in seven species of Arctic seabirds from northern
      Baffin Bay.
AB  - Organochlorine contaminants (OCs) were determined in liver and fat of seven
      species of seabirds (Alle alle, Uria lomvia, Cepphus grylle, Rissa tridactyla,
      Pagophila eburnea, Larus hyperboreus, and Fulmaris glacialis) collected in
      May/June 1998 from the Northwater Polynya in northern Baffin Bay. OC
      concentrations ranged over an order of magnitude between seabird species and OC
      groups, with PCBs having the highest concentrations followed by DDT, chlordane,
      HCH and ClBz. Positive relationships between delta15N (estimator of trophic
      level) and OC concentrations (lipid basis) were found for all OC groups, showing
      that trophic position and biomagnification significantly influence OC
      concentrations in Arctic seabirds. Concentrations of a number of OCs in
      particular species (e.g., HCH in P. eburnean) were lower than expected based on
      delta15N and was attributed to biotransformation. P. eburnea and F. glacialis,
      which scavenge, and R. tridactyla, which migrate from the south, were
      consistently above the delta15N-OC regression providing evidence that these
      variables can elevate OC concentrations. Stable isotope measurements in muscle
      may not be suitable for identifying past scavenging events by seabirds. OC
      relative proportions were related to trophic position and phylogeny, showing that
      OC biotransformation varies between seabird groups. Trophic level, migration,
      scavenging and biotransformation all play important roles in the OCs found in
      Arctic seabirds.

PMID- 14720476
TI  - Suitability of altai wildrye (Elymus angustus) and slender wheatgrass (Agropyron
      trachycaulum) for initial reclamation of saline composite tailings of oil sands.
AB  - The reclamation of freshly produced composite or consolidated tailings (CT) is a
      challenge for the Oil Sands Industry in the boreal forest of Western Canada. CT
      tailings materials are characterized by a relatively high salinity (dominated by
      sodium, sulphate and chloride) and a high pH (8-9). A greenhouse study was
      conducted to determine the germination, survival, injury and early plant growth
      of two grass species recommended for land reclamation, altai wildrye (Elymus
      angustus Trin) and slender wheatgrass (Agropyron trachycaulum Link Malte),
      growing in two different oil sand CT tailings (alum-CT and gypsum-CT), with and
      without peat amendment. Ion accumulation in the resulting plant tissues was
      determined. Our results showed that slender wheatgrass was most affected by the
      tailings at the germination stage, while for altai wildrye, the early growth
      stage was the most sensitive stage. Alum-CT had similar or less negative impact
      on plants than gypsum-CT. Amendment of CT with peat limited the reduction in
      germination and growth that was recorded in plants growing directly in CT. Based
      on these results, recommendations were made to improve reclamation strategies.

PMID- 14720477
TI  - Long-term changes of acidifying deposition in Finland (1973-2000).
AB  - The long-term changes of acidifying deposition in Finland during the period 1973
      2000 were studied using bulk deposition data from 19 stations belonging to the
      national monitoring network. The regional-scale approach (southern, central and
      northern Finland) was used for trend assessment with respect to implementation of
      European sulphur (S) emission reduction amendments involving deposition changes
      prior to (1973-1985) and after (1986-2000) the agreements (S protocols in 1985
      and 1994). There were no marked changes in sulphate deposition between the 1970s
      and 1980s and consistent trends in 1973-1985 were not observed. Deposition of
      nitrogen (N) compounds, particularly NO3-N, were increasing between the 1970s and
      1980s. Deposition of base cations exhibited a slight decline throughout the 1970s
      and 1980s. Decrease of calcium and magnesium deposition without corresponding
      decrease in sulphate resulted in increased acidifying potential (AP) of
      deposition. Due to successful implementation of S (and N) emission reduction
      measures, sulphate deposition has decreased substantially (30% in northern and up
      to 60% in southern Finland) since the late 1980s. N deposition also decreased,
      but less than S deposition. Base cation deposition has also declined
      substantially, but this decline appeared to be leveling off during the 1990s,
      accounting for the decrease of AP in deposition. The observed deposition pattern
      is in agreement with the on-going biochemical recovery of acidified small Finnish
      lakes taking place since the early 1990s.

PMID- 14720478
TI  - Vitellogenin content in European eel (Anguilla anguilla) in Flanders, Belgium.
AB  - As part of a large-scale monitoring program of bioaccumulating contaminants in
      the European eel (Anguilla anguilla) in Flanders (Belgium), we investigated
      potential effects of xenoestrogens in these fish. The present paper describes the
      results of the plasma vitellogenin (VTG) content, measured in 142 eels sampled at
      20 different locations, in relation to the internal pollution levels. To validate
      the blood VTG assays, a small number of eels (n=8) was exposed to 10 microg
      ethinylestradiol/l (EE2) for 9 days. In this experiment, VTG was detected as a
      protein with a molecular weight of 214 kDa and confirmed by Western blotting.
      Compared with the solvent controls, significantly higher concentrations of VTG
      were measured in EE2 exposed eel. However, the VTG content was relatively low
      compared with other fish species exposed to high concentrations of estrogens. The
      plasma VTG content of eels from the field study was very low, despite a very high
      internal load of endocrine disrupters. These results, together with previously
      published studies, suggest that immature yellow European eel might not be the
      best sentinel species to study the effects of estrogenic compounds on VTG levels
      of wild fish populations.

PMID- 14720479
TI  - Phytoextraction crop disposal--an unsolved problem.
AB  - Several methods of contaminated crop disposal after phytoextraction process
      (composting, compaction, incineration, ashing, pyrolysis, direct disposal, liquid
      extraction) have been described. Advantages and disadvantages of methods are
      presented and discussed. Composting, compaction and pyrolysis are the
      pretreatment steps, since significant amount of contaminated biomass will still
      exist after each of the process. Four methods of final disposal were
      distinguished: incineration, direct disposal, ashing and liquid extraction. Among
      them, incineration (smelting) is proposed as the most feasible, economically
      acceptable and environmentally sound.

PMID- 14720480
TI  - Organochlorine residues in harbour porpoises from Southwest Greenland.
AB  - During the 1995 hunting season, 75 harbour porpoises (Phocoena phocoena) were
      sampled in three locations in West Greenland: Maniitsoq, Nuuk, and Paamiut. Sex,
      age, morphometrics, reproductive condition, and organochlorine compound (OC)
      levels in blubber were determined for each individual. OC levels were extremely
      low and, therefore considered unlikely to affect the population adversely: mean
      blubber concentrations, expressed on lipid weight basis were 1.98 (S.D.=1.1)
      mg/kg for PCBs, 2.76 (S.D.=1.66) mg/kg for tDDT and 0.21 (S.D.=0.11) mg/kg for
      HCB. No statistical differences were observed among individuals caught in the
      various locations. OC concentrations showed statistically significant positive
      associations with age in males but negative in females; consequently, mature
      females presented lower pollutant loads than their male counterparts. Juveniles
      did not show differences between sexes. A higher proportion of less chlorinated
      and more metabolizable polychlorinated biphenyls (PCBs) compared to tPCBs was
      found in calves (age< or =1) than in mature females, indicating that the feeding
      habits of these two groups differ and that a greater transfer of less chlorinated
      compounds is passed from females to their pups through lactation and parturition.
      Harbour porpoises significantly contribute to the dietary intake of OCs by local
      Inuit populations. This contribution could be reduced if mature males were
      selectively avoided; however, current hunting procedures make this selection
      impracticable.

PMID- 14720481
TI  - Antioxidant responses to benzo[a]pyrene and Aroclor 1254 exposure in the green
      lipped mussel, Perna viridis.
AB  - In this study, the green-lipped mussel, Perna viridis (L.), was exposed to two
      concentrations of benzo[a]pyrene (B[a]P) (0.3 microg l(-1); 3 microg l(-1)) and
      two concentrations of Aroclor 1254 (0.5 microg l(-1); 5 microg l(-1)). In
      addition, a mixture of the contaminants was used (0.3 microg l(-1) B[a]P+0.5
      microg l(-1) Aroclor 1254; 3 microg l(-1) B[a]P+5 microg l(-1) Aroclor 1254). All
      concentrations were nominal. A suite of enzymes [glutathione S transferase (GST),
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR)], glutathione (GSH) level and lipid peroxidation (LPO)
      in the mussel gill and hepatopancreas were monitored over 18 days. CAT and GSH in
      gill tissue were positively correlated with concentration of Aroclor 1254.
      Activity of hepatic GST and SOD was significantly related to body burden of
      Aroclor 1254. LPO, GR and GPx in gill and hepatopancreas and hepatic GST were
      positively correlated with B[a]P concentration. The results indicate the
      importance of using biomarkers specific to the type of contaminant(s) that are
      likely to be present. Controlled laboratory experiments, such as this study, are
      useful in ascertaining biomarkers suitable for use with complex contaminant
      mixtures in the marine environment.

PMID- 14720482
TI  - A cumulative ozone uptake-response relationship for the growth of Norway spruce
      saplings.
AB  - Norway spruce saplings [Picea abies (L.) Karst.] were exposed during four growing
      seasons to different ozone treatments in open-top chambers: charcoal filtered air
      (CF), non-filtered air (NF) and non-filtered air with extra ozone (NF+,
      1.4xambient concentrations). The CF and NF+ ozone treatments were combined with
      phosphorous deficiency and drought stress treatments. The total biomass of the
      trees was harvested at different intervals during the experimental period. The
      ozone uptake to current-year needles of the Norway spruce saplings was estimated
      using a multiplicative stomatal conductance simulation model. There was a highly
      significant correlation between the reduction of total biomass and the estimated
      cumulative ozone uptake, which did not vary when different thresholds were
      applied for the rate of ozone uptake. The reduction of the total biomass was
      estimated to 1% per 10 mmol m(-2) cumulated ozone uptake, on a projected needle
      area basis.

PMID- 14720483
TI  - The quantification and distribution of pollution Pb at a woodland in rural south
      central Ontario, Canada.
AB  - Lead concentrations and Pb isotope ratios were measured in the forest floor,
      mineral soil and vegetation at a white pine and a sugar maple stand in a woodland
      in south central Ontario. Lead concentrations decreased and 206Pb/207Pb ratios
      increased with mineral soil depth reflecting the mixing of pollution and natural
      Pb sources. Lead concentrations and 206Pb/207Pb ratios at 20-30 cm depth were
      approximately 6-7 mg/kg and 1.31-1.32, respectively. Assuming an integrated
      206Pb/207Pb ratio in deposition over time of 1.18, estimated from lichen
      measurements and published data for the region, approximately 65% of Pb in the
      surface (0-1 cm) mineral soil is from anthropogenic sources. Approximately 90% of
      pollution Pb is found in the 0-10 cm soil layer (Ah) and less than 3% of the
      pollution Pb is present in the forest biomass and mull-type forest floor
      combined. Despite low Pb concentrations in vegetation (<2.5 mg/kg), we estimate
      that between 65 and 100% of the Pb in vegetation and approximately 75% of the Pb
      in the forest floor is from pollution sources. In total, the pollution Pb burdens
      at the pine and maple stands are estimated to be 860 and 750 mg/m2, respectively.

PMID- 14720484
TI  - Priming effects on PAH degradation and ecotoxicity during a phytoremediation
      experiment.
AB  - An experiment was conducted to distinguish priming effects from the effects of
      phytoremediation of a creosote-polluted soil. The concentration of 13 polycyclic
      aromatic hydrocarbons (PAHs), and their combined soil toxicity (using four
      bioassays), was determined on recently excavated, homogenized soil and on such
      soil subjected to a time-course phytoremediation experiment with lucerne. The
      results showed a high priming effect, with minor positive and synergistic effects
      of planting and fertilization on PAH degradation rates. At the end of the
      experiment, PAH degradation reached 86% of the initial 519 mg PAHs kg(-1). Two of
      the four toxicity tests (bioluminescence inhibition and ostracod growth
      inhibition) corroborated the chemical data for residual PAHs, and indicated a
      significant reduction in soil toxicity. We conclude that priming effects can
      easily surpass treatment effects, and that an unintentional pre-incubation that
      ignores these effects can jeopardize the full quantitative assessment of in situ
      bioremediation of contaminated soil.

PMID- 14720485
TI  - Effects of incremental increases in silt load on the cardiovascular performance
      of riverine and lacustrine rock bass, Ambloplites rupestris.
AB  - Rock bass (Ambloplites rupestris) are a widespread centrarchid species with both
      riverine and lacustrine populations. After precipitation events, rivers often
      carry elevated silt loads, where as lakes generally remain free from suspended
      silt and sediment. To examine the physiological effects of silt on rock bass, we
      conducted a series of experiments using fish from Lake Opinicon and the Grand
      River in Ontario. Ultrasonic Doppler flow probes were surgically affixed around
      the ventral aorta to monitor cardiovascular performance. After recovery from
      surgery replicated treatment groups were exposed to incremental increases in silt
      load (made from bentonite slurry), while cardiac output and its two components,
      heart rate and stroke volume, were measured simultaneously. Although both groups
      of rock bass responded significantly to low concentrations of silt (10 NTU), the
      response by riverine rock bass was rapidly extinguished by acclimation or
      physiological adjustment. Compensatory mechanisms to minimize cardiac (and
      respiratory) disruption attributable to increases in suspended silt appear to be
      inherent in rock bass of riverine origin. These fish appear to fully compensate
      for interference in gas exchange at the gill surfaces 60 min after initial
      exposure. In contrast, individual lacustrine rock bass were highly variable in
      their response to elevated silt concentrations. Changes in stroke volume and
      cardiac output suggested no clear compensatory mechanism or strategy to cope with
      increased silt levels.

PMID- 14720486
TI  - Invariant chlorine isotopic signatures during microbial PCB reductive
      dechlorination.
AB  - In order to develop more robust insight into the natural attenuation of
      polychlorinated biphenyls (PCBs), the chlorine isotopic composition of residual
      2,3,4,5-tetrachlorobiphenyl (2,3,4,5-CB) was monitored as it underwent microbial
      reductive dechlorination to 2,3,5-trichlorobiphenyl (2,3,5-CB) in laboratory
      cultures. Reverse-phase high performance liquid chromatography (HPLC) was
      employed to isolate the former compound from the experimental matrix for
      delta37Cl measurement. No detectable isotopic fractionation was observed over the
      90 day incubation with sterile control, standard, and inoculated samples all
      exhibiting delta37Cl values with a range of approximately 0.5 per thousand. These
      results show that this type of biological activity can be discriminated from
      other transformations by the absence of a measurable isotope effect during
      microbial reductive dechlorination. The utility of HPLC isolation for compound
      specific delta37Cl analyses of environmentally relevant species is also
      demonstrated.

PMID- 14720487
TI  - Cost containment analysis of childhood vaccination against varicella in Israel.
AB  - OBJECTIVES: The low cost of safe and effective vaccines prompted a cost
      containment evaluation of a nationwide vaccination campaign against varicella.
      METHODS: A model incorporating demographic, epidemiologic and economic data from
      Israeli sources (supplemented by data from International literature) was
      constructed to estimate the decrease in morbidity and the consequent reductions
      in treatment costs and time-off work of a nationwide programme vaccinating
      children at 12 months. RESULTS: A policy of aiming to immunize a cohort of all 1
      year-olds in Israel in the year 2002, for an annual cost of $1.10 million to the
      health services and $1.27 million to society (including lost work and transport
      costs), would reduce the number of cases of varicella during the lifetime of a
      cohort from 123,984 to 10,170 cases. This morbidity reduction would reduce
      national expenditures by $1.80 million in health service resources alone and by
      $24.5 million to society, mainly due to inaverted work absences. In addition an
      estimated 0.93 lives, representing 38.6 life years will be saved in the cohort.
      CONCLUSIONS: Under an assumption of neutrality relating to the potential effects
      of vaccination on herpes zoster virus, our model based calculations show that a
      national varicella vaccination programme is likely to be cost saving, not only
      from a societal perspective but also from the narrower health service
      perspective.

PMID- 14720488
TI  - Evidence based paediatrics: review of BTS guidelines for the management of
      community acquired pneumonia in children.
AB  - Community acquired pneumonia is a common illness with significant morbidity and
      mortality in children and a high cost to society. Guidelines for management in
      the UK were issued by the British Thoracic Society in 2002 [Thorax 57 (2002) 1].
      This review summarises the guidelines with emphasis on aetiology, investigations
      and antibiotic treatment.

PMID- 14720489
TI  - Burden and cost of imported infections admitted to infectious diseases units in
      England and Wales in 1998 and 1999.
AB  - BACKGROUND: International travel from the UK has been rising, and the number of
      imported infections has increased. This study aimed to describe the number,
      nature, origin, clinical burden and cost of imported infections treated in
      infectious disease units (IDU) in England and Wales. METHOD: Information about
      all admissions in 1998 and 1999 with illnesses considered to have been acquired
      during their most recent travel abroad was collected retrospectively by IDUs
      using a pre-piloted questionnaire. RESULTS AND ANALYSIS: Four of the 23 IDUs in
      England and Wales were able to complete the questionnaires. They reported a total
      of 421 travel related admissions during the 2-year period. Three hundred and
      ninety-two of these cases were attributed to infectious causes, and of these a
      discharge diagnosis was made for 340 cases. The total number of bed days used to
      treat cases of imported infection was 2918. The most common diagnosis was
      malaria. The odds ratio that cases of imported infection were malaria was highest
      following visits to Africa. The average cost per bed day on the IDUs was around
      pound sterling 100, and on this basis, the total cost of treating imported
      infections on the four IDUs in 2 years was around pound sterling 289,000. The
      relative risk of acquiring an imported infection requiring treatment on an IDU
      was greatest for travellers to Africa. CONCLUSIONS: From this study, the estimate
      of the total annual cost of IDU treatment for imported infections in England and
      Wales is in excess of pound sterling 800,000. Many cases may be preventable with
      prophylactic medication and vaccination and travel advice on risk reduction.
      Further information about imported infections would be useful to inform travel
      medicine services, other clinicians and travellers about the health risks
      associated with travel to specific areas, and help to target and assess the cost
      effectiveness of preventative measures.

PMID- 14720490
TI  - Pertussis--a re-emerging infection?
AB  - Seven cases of pertussis in patients aged between 1 and 6 months detected over 3
      months were reported. Paroxysmal cough (six cases), post-tussive vomiting (three
      cases) and poor feeding (three cases) were the most common presenting symptoms.
      Bordetella pertussis was isolated from six patients. The total leucocyte counts
      were mildly increased (10.8-15.6x10(9)/L). The lymphocyte counts were markly
      raised (59-73%) and appear to be useful indicators of pertussis. It appears that
      herd immunity does not offer adequate protection to the vulnerable group even in
      well-vaccinated populations. High vaccination coverage should be maintained, and
      vaccination should be given as early an age as possible. Aggressive efforts to
      identify cases and contacts are essential. Health care workers should have a high
      index of suspicion for pertussis, in particular for those with paroxysmal cough
      and high lymphocyte counts so as to give timely diagnosis and treatment.

PMID- 14720491
TI  - Genotypes and phenotypes of Shiga toxin producing-Escherichia coli isolated from
      healthy cattle in Thailand.
AB  - Shiga toxin producing-Escherichia coli (STEC) has not yet been identified as an
      important aetiologic agent of human disease in Thailand. To evaluate the
      potential for STEC to contribute to human disease in Thailand, 139 fecal samples
      were collected from healthy cattle from five different provinces and analysed by
      genotypic and phenotypic methods for STEC. Of 139 samples, 27 (19.4%) were
      positive for stx1 and/or stx2 by multiplex polymerase chain reaction, or for O157
      lipopolysaccharide (LPS) by immunoassay. Isolates positive for stx and/or O157
      were subdivided into 49 strains that varied in the presence of the virulence
      determinants stx1+/stx2+ (22 strains), stx2+ (22 strains), stx1+ (4 strains), and
      O157 LPS (1 strain). Within these 49 distinguishable strains, other virulence
      determinants varied as follows: hlyA+ (77.6%), eae+ and tir+ (4.1%), and katP+
      (6.12%). The most predominant profile (22 isolates) was stx1+/stx2+, eae-, tir-,
      etpD-, hlyA+, katP-. For further characterization of the isolated strains by two
      molecular typing assays, plasmid profiles and ERIC PCR were performed. The
      results suggest that the genetic and phenotypic profiles of STEC associated with
      human disease are not prevalent at this time in cattle in Thailand.

PMID- 14720492
TI  - Frequency and characteristics of diarrhoeagenic Escherichia coli strains isolated
      from children with and without diarrhoea in Rio de Janeiro, Brazil.
AB  - The frequency of diarrhoeagenic Escherichia coli (DEC) strains was investigated
      in 253 children up to 3 years old, with (patient group, PG, 199 children) and
      without (control group, CG, 54 children) diarrhoea, living in Rio de Janeiro,
      Brazil. DEC strains were detected in 70 (27.6%) children, including 54 (27.1%)
      with diarrhoea and 16 (29.6%) without diarrhoea. Enteroaggregative E. coli (EAEC)
      was the most frequent DEC category, accounting for 14.6% of the isolates in the
      PG and for 11.1% in the CG. E. coli strains carrying enteropathogenic E. coli
      (EPEC) virulence markers showed higher incidence in the CG (12.9%) than in the PG
      (8.0%). E. coli strains belonging to non-classical EPEC groups that carried eae
      only or eae and bfpA, designated as attaching-effacing E. coli (AEEC) were the
      most frequent (79.1%). Simultaneous presence of multiple EPEC virulence factors
      (EAF/eae/bfpA) were only detected among strains isolated from the PG.
      Enterotoxigenic E. coli (ETEC) strains were isolated from 5.5% of the children in
      the CG and from 3.5% of those in the PG. Most of the ETEC isolates were LT-probe
      positive (70%) and none carried both LT-I and ST-I probe sequences. One
      enteroinvasive E. coli (EIEC) strain was recovered from a child with diarrhoea.
      No stx-probe positive E. coli strains were detected. Overall, DEC strains were
      not found to be significantly associated with diarrhoea (p>0.05). However, the
      higher incidence of EAEC, the most frequent DEC category, among children with
      diarrhoea, suggests a potential role of EAEC as an important enteric pathogen in
      the community investigated.

PMID- 14720493
TI  - Serological evidence of Helicobacter pylori infection in UK South Asian and
      European populations: implications for gastric cancer and coronary heart disease.
AB  - OBJECTIVES: To describe the prevalence of serological evidence of infection with
      Helicobacter pylori among people of South Asian and European ethnic origins and
      to assess its association with prevalent coronary heart disease (CHD). METHODS:
      We used a quantitative method to compare IgG antibodies to H. pylori in a
      population sample of 300 South Asians and 302 Europeans in Newcastle upon Tyne,
      UK. RESULTS: For men and women, respectively, H. pylori IgG (95% confidence
      interval) was 16.7 microg/ml (13.9, 20.2) and 11.3 (9.4, 13.5) among Europeans
      and 11.6 (9.8, 13.7) and 14.3 (12.1, 16.9) among South Asians. Levels were higher
      in older participants and in those of lower socioeconomic status. The ratio of
      geometric mean IgG, (95% confidence interval) adjusted for age, sex and
      socioeconomic status, in those with and without CHD was 1.02 (0.49, 2.11) among
      Europeans and 1.79 (1.01, 3.17) among South Asians. Antibodies against
      staphylococcal enterotoxins A and B were higher among South Asians than
      Europeans. CONCLUSIONS: The prevalence of H. pylori infection among UK South
      Asians does not reflect that of their countries of origin, nor their lower
      prevalence of gastric cancer. The association with CHD in South Asians requires
      corroboration in other studies.

PMID- 14720494
TI  - The pathogenesis of dermatophyte infections in human skin sections.
AB  - AIM: A novel ex vivo model for the study of adherence and invasion of
      dermatophytes to the stratum corneum was developed. MATERIALS AND METHODS: A skin
      of full epidermis thickness was infected by spores of Trichophyton mentagrophytes
      and examined after various periods of time by scanning and transmission electron
      microscopy. RESULTS: After 12 h of inoculation a tenacious adherence between the
      spores and the stratum corneum was observed. There was a time dependent increase
      in the number of spores adhered to this surface. By 24 h, germination had
      commenced. The initial growth of germ tubes occurred extracellularly to the
      corneocytes. Three days after inoculation, the most prominent feature was
      proliferation of fungal hyphae and penetration of mycelium through the outer
      keratinocyte layer which is followed by invasion of the outer stratum corneum.
      CONCLUSION: The model introduced in the present study may contribute to a better
      understanding of the nature of the interaction between dermatophytes and skin
      cells in dermatophytosis process.

PMID- 14720495
TI  - Early diagnosis of candidiasis in non-neutropenic critically ill patients.
AB  - OBJECTIVE: To determine a method for the early diagnosis of candidiasis in non
      neutropenic critically ill patients in order to reduce mortality. METHODS: A
      prospective study in non-neutropenic critically patients in whom Candida spp.
      were detected, was made in an intensive care unit (ICU) during an 8-year period
      from 3389 patients admitted. A diagnostic and therapeutic protocol was designed.
      Invasive candidiasis was defined according to dissemination and multifocality.
      RESULTS: Candida spp. were found in 145 cases (4.3%): 120 (83%) were considered
      as invasive candidiasis and 25 as colonisation (17%). The hospital mortality was
      46% (67/145). A post-mortem study was carried out in 54% (36/67) of hospital
      deaths. Candida albicans was the most frequently isolated species (87%), followed
      by Candida glabrata (18%). There were 24 candidemias and three cases of
      endophtalmitis. Digestive and respiratory samples and non-C. albicans yeasts were
      risk factors for invasive candidiasis. The mortality rate was related
      statistically to invasive candidiasis and inversely to the appropriate antifungal
      treatment. CONCLUSIONS: Invasive candidiasis is related to digestive and
      respiratory samples and to the presence of non-C. albicans species. A simpler
      definition of invasive candidiasis in non-neutropenic critically ill patients
      will permit more rapid and accurate specific antifungal therapy.

PMID- 14720496
TI  - Central nervous system paracoccidioidomycosis: clinical features and laboratorial
      findings.
AB  - OBJECTIVE: To study prospectively the clinical features and laboratorial
      characteristics of 24 patients with central nervous system (CNS) involvement with
      paracoccidioidomycosis (PCM). PCM is an infectious disease caused by the
      dimorphic fungus Paracoccidioides brasiliensis, endemic in subtropical areas of
      Central and South America. METHODS: From 173 cases of PCM, 24 (13.9%) had CNS
      involvement (NPCM) and were studied prospectively from 1993 to 1997. In all the
      patients, the diagnosis of systemic PCM was made by the demonstration of the P.
      brasiliensis organisms or positive serology, DID (double immunodiffusion). In
      seven cases the diagnosis was made by means of a CNS biopsy. CNS clinical
      manifestations, neuroimaging (CT or MRI) and CSF cytochemical characteristics
      were reported. RESULTS: The mean age was 44 years (range 25-72 years); 23
      patients were male, only one was female. Neurological symptoms began before
      systemic symptoms in 21%; simultaneously in 33%, and after systemic symptoms in
      46%. Epilepsy was the more frequent neurological presentation (44%). Twenty-three
      cases had parenchymatous involvement and in two of these cases there was an
      association with meningitis and one case had spinal cord involvement. Lesions
      were more frequent in the brain hemispheres (69%), in 65% there were multiple
      granuloma characterized by hypodense images with annular or nodular enhancing.
      All cases were treated with sulphamethoxazole-trimethoprin. Four patients died,
      while 20 patients showed a good therapeutic response. CONCLUSION: NPCM should
      always be considered in the differential diagnosis of expanding lesions of the
      CNS and meningoencephalitis. Being alert to this diagnosis depends on knowledge
      of epidemiology. There was good response to sulphamethoxazole-trimethoprin
      treatment.

PMID- 14720497
TI  - Serum procalcitonin concentration in patients with Kawasaki disease.
AB  - BACKGROUND: Procalcitonin (PCT) is a new parameter of inflammation, the clinical
      usefulness of which is currently being evaluated. MATERIALS AND METHODS: We
      determined simultaneously the serum concentrations of PCT and C-reactive protein
      (CRP) as well as the white blood cell (WBC) count in 25 patients with Kawasaki
      disease (KD), 17 with bacterial infections, 10 with systemic autoimmune diseases,
      17 with viral infections and 18 healthy children. The optimal cut-off value of
      each parameter for predicting coronary aneurysms was determined using receiver
      operating characteristic curves. RESULTS: Significantly higher serum
      concentrations of PCT were observed in patients with KD (2.3 +/- 3.0 ng/ml) and
      bacterial infections (2.2 +/- 2.9 ng/ml) than in patients with autoimmune
      diseases (0.4 +/- 0.4 ng/ml) or viral infections (0.4 +/- 0.3 ng/ml), or in
      healthy children (0.2 +/- 0.1 ng/ml). The serum PCT but not the WBC count or CRP,
      differentiated the KD patients from the patients with autoimmune diseases. The
      optimal cut-off value of 3.0 ng/ml of PCT increased the prediction rate of
      coronary aneurysms that subsequently occurred in 4 (16%) patients with KD.
      CONCLUSIONS: The serum PCT may be clinically useful for determining the severity
      of KD and for narrowing the differential diagnosis of patients with inflammatory
      diseases.

PMID- 14720498
TI  - Enterococcus casseliflavus bacteremia. Case report and literature review.
AB  - Motile Enterococci are rare causes of enterococcal bacteremia, usually in
      immunocompromised patients. We describe a case of polymicrobial bacteremia,
      including Enterococcus casseliflavus, Escherichia coli, and Morganella morganii,
      in an 80-year old woman, shortly after a liver biopsy performed to exclude
      cholangiocarcinoma. We further discuss the unique genetic characteristics and the
      clinical significance of such isolates, such as their intrinsic resistance to
      vancomycin, and the low virulence exhibited clinically. Further workup on the
      mechanisms of motile Enterococci resistance to vancomycin could probably yield
      useful information in achieving new ways of facing resistance attributed to the
      more usual, and malignant Enterococci.

PMID- 14720500
TI  - Does complementary medicine have a role in infectious diseases?

PMID- 14720499
TI  - A malaria outbreak following a British military deployment to Sierra Leone.

PMID- 14720501
TI  - Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase
      activation and adhesion molecule expression in endothelial cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates expression of endothelial cell
      (EC) genes that may promote atherosclerosis in part by an activation of mitogen
      activated protein (MAP) kinases. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]
      one), a selenoorganic compound, is effective for acute ischemic stroke; however,
      its effect on EC has not yet been elucidated. We examined the effect of ebselen
      on TNF-alpha-induced MAP kinase activation and adhesion molecule expression in
      cultured human umbilical vein endothelial cells (HUVEC). Extracellular signal
      regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 were rapidly and
      significantly activated by TNF-alpha in HUVEC. TNF-alpha-induced JNK activation
      was inhibited by ebselen, whereas ERK1/2 and p38 were not affected. Apoptosis
      signal-regulated kinase 1 (ASK1) was suggested to be involved in TNF-alpha
      induced JNK activation because transfection of kinase-inactive ASK1 inhibited TNF
      alpha-induced JNK activation. Ebselen inhibited TNF-alpha-induced TNF receptor
      associated factor 2 (TRAF2)-ASK1 complex formation and phosphorylation of stress
      activated protein kinase ERK kinase 1 (SEK1), which is an upstream signaling
      molecule of JNK. Finally, TNF-alpha-induced activator protein-1 (AP-1) and
      nuclear factor-kappaB (NF-kappaB) activation and resultant intracellular adhesion
      molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions
      were inhibited by ebselen. Specific inhibitors for JNK and NF-kappaB also
      inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expressions in HUVEC. These
      findings suggest that ebselen prevents TNF-alpha-induced EC activation through
      the inhibition of TRAF2-ASK1-SEK1 signaling pathway, which leads to JNK
      activation. Inhibition of JNK by ebselen may imply its usefulness for the
      prevention of atherosclerosis relevant to EC activation.

PMID- 14720502
TI  - A blockade in Wnt signaling is activated following the differentiation of F9
      teratocarcinoma cells.
AB  - Aberrant activation of the Wnt signaling pathway is a common event in human tumor
      progression. Wnt signaling has also been implicated in maintaining a variety of
      adult and embryonic stem cells by imposing a restraint to differentiation. To
      understand the effect of Wnt signaling on the differentiation of epithelial
      cells, we used mouse teratocarcinoma F9 cells as a model. The F9 cells can be
      differentiated into visceral endoderm (VE) resembling absorptive columnar
      epithelial cells. We performed comparative gene expression analysis on retinoic
      acid-differentiated and undifferentiated F9 cells and confirmed that markers of
      VE and intestinal epithelium were induced upon differentiation. The induction of
      these markers by retinoic acid was reduced in the presence of Wnt, although Wnt
      alone did not change their expression. This suggests that Wnt signaling inhibited
      the differentiation of F9 cells by altering gene expression. This inhibition was
      also reflected in the morphology of the F9 cells as their apical-basal polarity
      was disrupted by inclusion of Wnt during differentiation. These results support a
      model in which Wnt modulates the expression of genes required for normal terminal
      differentiation of the stem cells. However, it follows that progenitor cells must
      escape from Wnt signaling to attain the differentiated state. Accordingly, we
      found that differentiated F9 cells no longer responded to Wnt and that a blockade
      in Wnt signaling occurred upstream of Axin. Consistent with this, Wnt negative
      regulators, such as Dickkopf-1 and Disabled-2, were induced upon the
      differentiation of F9 cells. We propose that a similar system to produce Wnt
      inhibitors regulates homeostasis of certain stem cell compartments in vivo.

PMID- 14720503
TI  - Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion
      in mucoepidermoid carcinomas and benign Warthin's tumors.
AB  - Chromosome translocations in neoplasia commonly result in fusion genes that may
      encode either novel fusion proteins or normal, but ectopically expressed
      proteins. Here we report the cloning of a novel fusion gene in a common type of
      salivary and bronchial gland tumor, mucoepidermoid carcinomas (MEC), as well as
      in benign Warthin's tumors (WATs). The fusion, which results from a t(11;19)(q21
      22;p13) translocation, creates a chimeric gene in which exon 1 of a novel gene of
      unknown function, designated WAMTP1, is linked to exons 2-5 of the recently
      identified Mastermind-like Notch coactivator MAML2. In the fusion protein, the N
      terminal basic domain of MAML2, which is required for binding to intracellular
      Notch (Notch ICD), is replaced by an unrelated N-terminal sequence from WAMTP1.
      Mutation analysis of the N-terminus of WAMTP1-MAML2 identified two regions of
      importance for nuclear localization (amino acids 11-20) and for colocalization
      with MAML2 and Notch1 ICD in nuclear granules (amino acids 21-42). Analyses of
      the Notch target genes HES5 and MASH1 in MEC tumors with and without the WAMTP1
      MAML2 fusion revealed upregulation of HES5 and downregulation of MASH1 in fusion
      positive MECs compared to normal salivary gland tissue and MECs lacking the
      fusion. These findings suggest that altered Notch signaling plays an important
      role in the genesis of benign and malignant neoplasms of salivary and bronchial
      gland origin.

PMID- 14720504
TI  - The effect of specific caspase inhibitors on TNF-alpha and butyrate-induced
      apoptosis of intestinal epithelial cells.
AB  - Tumour necrosis factor-alpha (TNF-alpha)-induced intestinal epithelial cell
      apoptosis may contribute to mucosal injury in inflammatory bowel disease.
      Inhibition of TNF-alpha-induced apoptosis, using specific caspase inhibitors
      could, therefore, be of benefit in the treatment of disease. In vitro, CaCo-2
      colonic epithelial cells are refractory to apoptosis induced by TNF-alpha alone;
      however, TNF-alpha can act synergistically with the short-chain fatty acid (SCFA)
      and colonic fermentation product, butyrate, to promote apoptosis. TNF
      alpha/butyrate-induced apoptosis was characterised by nuclear condensation and
      fragmentation and caspase-3 activation. Inhibitors of caspase-8 (z-IETD.fmk) and
      caspase-10 (z-AEVD.fmk) significantly reduced TNF-alpha/butyrate-induced
      apoptosis, based on nuclear morphology and terminal deoxynucleotide transferase
      mediated dUTP-biotin nick-end labelling (TUNEL), although caspase inhibition was
      associated with a significant increase in cells demonstrating atypical nuclear
      condensation. Inclusion of atypical cells in calculations of total cell death,
      still demonstrated that z-IETD.fmk and z-AEVD.fmk (in combination) significantly
      reduced cell death. Reduction in cell death was associated with maintenance of
      viable cell number. Transmembrane resistance was also used a measure of the
      ability of caspase inhibitors to prevent TNF-alpha/butyrate-mediated damage to
      epithelial monolayers. TNF-alpha/butyrate resulted in a significant fall in
      transmembrane resistance, which was prevented by pre-treatment with z-IETD.fmk,
      but not z-AEVD.fmk. In conclusion, synthetic caspase inhibitors can reduce the
      apoptotic response of CaCo-2 colonic epithelial cells to TNF-alpha/butyrate,
      improve the maintenance of viable cell numbers and block loss of transmembrane
      resistance. We hypothesise that caspase inhibition could be a useful therapeutic
      goal in the treatment of inflammatory bowel conditions, such as ulcerative
      colitis.

PMID- 14720505
TI  - Myodulin is a novel potential angiogenic factor in skeletal muscle.
AB  - We examined the expression and function of a gene we previously cloned from its
      downregulation in a muscle atrophy model. The encoded protein was named myodulin
      because of sequence homologies with the cartilage-specific chondromodulin-I (ChM
      I) protein, its restricted expression in skeletal muscle tissue, and its
      modulating properties on vascular endothelial cells described here. We
      investigated the expression of myodulin in muscle fibers and cultured muscle
      cells. Myodulin RNA messengers were found in muscle fibers and their tendon
      extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of
      a muscle cell surface protein. Myodulin functions were assessed from similarities
      with chondromodulin-I. Coculture experiments using C(2)C(12) mouse myoblasts or
      myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular
      endothelial cells revealed that myodulin had a very active role in the invasive
      action of endothelial cells, without any evidence of extracellular myodulin
      secretion. Our results suggest that myodulin may be a muscle angiogenic factor
      operating through direct cell-to-cell interactions. This role is consistent with
      the correlation between modulations in myodulin expression and modifications in
      muscle microvascularization associated with activity-dependent muscle mass
      variations.

PMID- 14720506
TI  - The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription
      factors in epithelial cells.
AB  - ZO-2 is a membrane-associated guanylate kinase (MAGUK) protein present at the
      tight junction (TJ) of epithelial cells. While confluent monolayers have ZO-2 at
      their cellular borders, sparse cultures conspicuously show ZO-2 at the nuclei. To
      study the role of nuclear ZO-2, we tested by pull-down assays and gel shift
      analysis the interaction between ZO-2 GST fusion proteins and different
      transcription factors. We identified the existence of a specific interaction of
      ZO-2 with Fos, Jun and C/EBP (CCAAT/enhancer binding protein). To analyze if this
      association is present "in vivo", we performed immunoprecipitation and
      immunolocalization experiments, which revealed an interaction of ZO-2 with Jun,
      Fos and C/EBP not only at the nucleus but also at the TJ region. To test if the
      association of ZO-2 with AP-1 (activator protein-1) modulates gene transcription,
      we performed reporter gene assays employing chloramphenicol acetyltransferase
      (CAT) constructs with promoters under the control of AP-1 sites. We observed that
      the co-transfected ZO-2 down-regulates CAT expression in a dose-dependent manner.
      Since ZO-2 is a multidomain protein, we proceeded to determine which region of
      the molecule is responsible for the modulation of gene expression, and observed
      that both the amino and the carboxyl domains are capable of inhibiting gene
      transcription.

PMID- 14720507
TI  - Rac regulates integrin-mediated endothelial cell adhesion and migration on
      laminin-8.
AB  - Blood vessel formation requires endothelial cell interactions with the
      extracellular matrix through cell surface receptors, and signaling events that
      control endothelial cell adhesion, migration, and lumen formation. Laminin-8
      (alpha4beta1gamma1) is present in all basement membranes of blood vessels in
      fetal and adult tissues, but despite its importance in vessel formation, its role
      in endothelial cell adhesion and migration remains undefined. We examined
      adhesion and migration of HMEC-1 human microvascular endothelial cells on laminin
      8 with an emphasis on the integrin-mediated signaling events, as compared with
      those on laminin-10/11 and fibronectin. We found that laminin-8 was less potent
      in HMEC-1 cell adhesion than laminin-1, laminin-10/11, and fibronectin, and
      mediated cell adhesion through alpha6beta1 integrin. Despite its weak cell
      adhesive activity, laminin-8 was as potent as laminin-10/11 in promoting cell
      migration. Cells adhering to laminin-8 displayed streaks of thin actin filaments
      and formed lamellipodia at the leading edge of the cells, as observed with cells
      adhering to laminin-10/11, while cells on fibronectin showed thick actin stress
      fibers and large focal adhesions. Pull-down assays of GTP-loaded Rho, Rac, and
      Cdc42 demonstrated that Rac, but not Rho or Cdc42, was preferentially activated
      on laminin-8 and laminin-10/11, when compared with fibronectin. Furthermore, a
      dominant-negative mutant of Rac suppressed cell spreading, lamellipodial
      formation, and migration on laminin-8, but not on fibronectin. These results,
      taken together, indicate that Rac is activated during endothelial cell adhesion
      to laminin-8, and is pivotal for alpha6beta1 integrin-mediated cell spreading and
      migration on laminin-8.

PMID- 14720508
TI  - Expression of the sarco/endoplasmic Ca(2+)-ATPase, SERCA1a, in fibroblasts
      induces the formation of organelle membrane arrays.
AB  - Members of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) family are
      transmembrane proteins that are essential for the function of intracellular
      Ca(2+) storage organelles. We found that overexpression of avian muscle SERCA1a
      in transfected mouse fibroblasts led to the appearance of tubular membrane
      bundles that we termed plaques. These structures were generated in transfected
      cells when SERCA1a protein expression approached the endogenous level measured in
      chicken skeletal muscle. Plaque membranes had associated ribosomes and contained
      endoplasmic reticulum (ER) proteins. Endogenous ER protein levels were not
      elevated in SERCA1a-expressing cells, indicating that plaques were not
      generalized proliferations of ER but rather a reorganization of existing
      organelle membrane. Plaque formation also was observed in cells expressing a
      green fluorescent protein-SERCA1a fusion protein (GFP-SERCA1a). GFP-SERCA1a
      molecules displayed extensive lateral mobility between plaques, suggesting the
      presence of membrane continuities between these structures. Plaques were induced
      in cells expressing cDNA encoding a catalytically silent SERCA1a mutant
      indicating that ER redistribution was driven by a structural feature of the
      enzyme. SERCA1a-induced plaque formation shares some characteristics of
      sarcoplasmic reticulum (SR) biogenesis during muscle differentiation, and high
      level SERCA1a expression in vivo may contribute to the formation of SR from ER
      during embryonic myogenesis.

PMID- 14720509
TI  - Sucrose-induced vacuolation results in increased expression of cholesterol
      biosynthesis and lysosomal genes.
AB  - Mammalian cells cultured in the presence of high concentrations of sucrose
      demonstrate large, phase-lucent, osmotically swollen vacuoles. Three normal human
      fibroblast cell lines exposed to 100 mM of sucrose for 24 h demonstrated
      increased expression of lysosomal, intracellular vesicle trafficking, cholesterol
      biosynthesis, and fatty acid metabolism genes. Most steps of the cholesterol
      biosynthesis pathway were upregulated including HMG CoA reductase, which
      catalyzes the rate-limiting step of cholesterol biosynthesis. The lysosomal genes
      neuraminidase, CLN3, and CLCN5 and the small GTP-binding proteins Rab7L1 and Arl7
      were also increased. A Rab7L1-GFP fusion protein was overexpressed in human
      fibroblasts and was demonstrated to localize primarily to the Golgi apparatus,
      and in some cells to the membranes bounding vesicles in the perinuclear region.
      Increased levels of the transcription factor C/EBP were found in nuclear extracts
      from cells exposed to sucrose for 12 h, relative to matched controls suggesting
      regulation of gene expression following sucrose-induced vacuolation may be
      coordinated, at least in part, by the transcription factor C/EBP. Sucrose-induced
      vacuolation is a useful model in which to study the regulation of lysosomal gene
      expression and biogenesis.

PMID- 14720510
TI  - Determination of downstream targets of FGF signalling using gene trap and cDNA
      subtractive approaches.
AB  - Signalling through the fibroblast growth factor family (FGF) of ligands is
      essential for normal mammalian embryonic development. At a cellular level, many
      details of the molecular basis of the signal transduction process have been
      uncovered, but our knowledge of the identity of the downstream effectors of the
      FGF signal in the developing embryo remains limited. We have used two independent
      approaches to begin to identify downstream targets of FGF signalling in the
      embryo: (1). a gene trap approach and (2). cDNA subtraction, using mouse
      embryonic stem (ES) cells as a cellular system representative of an early window
      on the developing embryo. Both approaches led to the identification of a number
      of targets of FGF signalling, and we provide data to show that the chaperone Mrj,
      the tumour antigen Tum, collapsin mediator response protein Crmp, a novel
      transcriptional repressor Nac1 and ribophorin are all differentially regulated
      following FGF signalling. Independent gene trapping of Mrj previously indicated a
      role for the gene in embryogenesis [Development 126 (1999) 1247], and we present
      transcript data implicating a number of the newly isolated FGF target genes in
      different embryonic processes.

PMID- 14720511
TI  - Extracellular proteinase inhibitor-accelerated apoptosis is associated with B
      cell activating factor in mammary epithelial cells.
AB  - The expression of extracellular proteinase inhibitor (Expi) gene was induced
      during the involution of mammary gland, when apoptosis occurs in this tissue.
      Transient transfection of Expi gene partially induced apoptosis of mammary
      epithelial HC11 cells. We developed the stable cell lines overexpressing Expi
      gene and found that overexpression of Expi accelerated apoptosis of mammary
      epithelial cells under serum starvation. To understand apoptosis pathway involved
      in the Expi overexpression, we examined the gene expression profile by using
      apoptosis gene array containing 243 genes. The subsequent confirmation of the
      altered gene expression by northern analysis demonstrated that overexpression of
      the Expi gene induced expression of several genes, which included B cell
      activating factor (BAFF), Bax, cytochrome c, caspase-9, caspase-3, caspase-6, and
      CIDE-A. From this study, we first demonstrate that BAFF is involved in mammary
      apoptosis. Furthermore, we have found that the Expi-accelerated apoptosis is
      mediated via BAFF receptor among three known BAFF receptors: BAFF receptor, tumor
      necrosis factor (TNF) receptor homologue TACI (transmembrane activator and CAML
      interactor), and BCMA (another TNFR homologue, B cell maturation antigen). Our
      studies also demonstrate that the use of apoptosis array provides an efficient
      tool to identify apoptosis pathway involved in gene transfection.

PMID- 14720512
TI  - Cyclin D1 expression and cell cycle response in DNA mismatch repair-deficient
      cells upon methylation and UV-C damage.
AB  - We have evaluated cell survival, apoptosis, and cell cycle responses in a panel
      of DNA mismatch repair (MMR)-deficient colon and prostate cancer cell lines after
      alkylation and UV-C damage. We show that although these MMR-deficient cells
      tolerate alkylation damage, they are as sensitive to UV-C-induced damage as are
      the MMR-proficient cells. MMR-proficient cells arrest in the S-G2 phase of the
      cell cycle and initiate apoptosis following alkylation damage, whereas MMR
      deficient cells continue proliferation. However, two prostate cancer cell lines
      that are MMR-deficient surprisingly arrest transiently in S-G2 after alkylation
      damage. Progression through G1 phase initially depends on the expression of one
      or more of the D-type cyclins (D1, D2, and/or D3). Analysis of cyclin D1
      expression shows an initial MMR-independent decrease in the protein level after
      alkylation as well as UV-C damage. At later time points, however, only DNA damage
      arrested cells showed decreased cyclin D1 levels irrespective of MMR status,
      indicating that reduced cyclin D1 could be a result of a smaller fraction of
      cells being in G1 phase rather than a result of an intact MMR system. Finally, we
      show that cyclin D1 is degraded by the proteasome in response to alkylation
      damage.

PMID- 14720513
TI  - Induction of neurites by the regulatory domains of PKCdelta and epsilon is
      counteracted by PKC catalytic activity and by the RhoA pathway.
AB  - We have shown that protein kinase C (PKC) epsilon, independently of its kinase
      activity, via its regulatory domain (RD), induces neurites in neuroblastoma
      cells. This study was designed to evaluate whether the same effect is obtained in
      nonmalignant neural cells and to dissect mechanisms mediating the effect.
      Overexpression of PKCepsilon resulted in neurite induction in two immortalised
      neural cell lines (HiB5 and RN33B). Phorbol ester potentiated neurite outgrowth
      from PKCepsilon-overexpressing cells and led to neurite induction in cells
      overexpressing PKCdelta. The effects were potentiated by blocking the PKC
      catalytic activity with GF109203X. Furthermore, kinase-inactive PKCdelta induced
      more neurites than the wild-type isoform. The isolated regulatory domains of
      novel PKC isoforms also induced neurites. Experiments with PKCdelta
      overexpressing HiB5 cells demonstrated that phorbol ester, even in the presence
      of a PKC inhibitor, led to a decrease in stress fibres, indicating an
      inactivation of RhoA. Active RhoA blocked PKC-induced neurite outgrowth, and
      inhibition of the RhoA effector ROCK led to neurite outgrowth. This demonstrates
      that neurite induction by the regulatory domain of PKCdelta can be counteracted
      by PKCdelta kinase activity, that PKC-induced neurite outgrowth is accompanied by
      stress fibre dismantling indicating an inactivation of RhoA, and that the RhoA
      pathway suppresses PKC-mediated neurite outgrowth.

PMID- 14720514
TI  - Direct evidence from siRNA-directed "knock down" that p16(INK4a) is required for
      human fibroblast senescence and for limiting ras-induced epithelial cell
      proliferation.
AB  - The selective pressure for disruption of the cyclin-dependent kinase inhibitor
      p16(INK4a) in human cancer has been postulated to reflect its role in mediating
      growth arrest, both in response to telomere erosion (replicative senescence) and
      to oncogene-induced and other "stress" signals. Given the known species-specific
      differences in regulation of senescence, we have tested this hypothesis in human,
      as opposed to rodent, cells by designing a small interfering RNA (siRNA) to knock
      down p16(INK4a) expression. Transfection of this siRNA into late-passage normal
      human diploid fibroblasts allowed at least temporary escape from entry into
      replicative senescence. Furthermore, in our in vitro model of early-stage, RAS
      induced thyroid tumorigenesis, sequential transfections with this siRNA allowed
      outgrowth of small clusters of proliferating epithelial cells, consistent with
      escape from the spontaneous "senescence", which normally curtails their
      proliferative response to mutant RAS. These data provide the first direct
      evidence that p16(INK4a) is necessary for the initiation of both telomere
      dependent and telomere-independent senescence in human cells.

PMID- 14720515
TI  - Wnt impacts growth and differentiation in ex vivo liver development.
AB  - The Wnt-beta-catenin pathway plays a role in liver growth and development. Here,
      we investigate the direct effect of Wnt-3A on ex vivo liver development. Livers
      from mouse embryos at day 10 were cultured in serum-free Wnt-3A-conditioned media
      alone or with HGF and insulin for 72 h and analyzed for histology, proliferation,
      apoptosis and lineage. Control cultures grown in serum-free conditions or Wnt-3A
      and sFRP-1 combination display loss of architecture and proliferation and
      increased apoptosis. In the presence of Wnt-3A, embryonic liver cultures show CK
      19-positive cells (biliary phenotype) displaying proliferation, minimal apoptosis
      and duct-like histological arrangement. HGF and Wnt combination exhibited normal
      histology as seen in the presence of 10% serum displaying stem cells, hepatocytes
      and primitive bile ducts. HGF, insulin and Wnt combination provided no additional
      benefits rather had an overall deleterious effect. Thus, Wnt supports biliary
      differentiation by enhancing stem cell specification, hepatocyte trans
      differentiation and promoting biliary survival. HGF and Wnt combination supports
      stem cells, hepatocytes and bile ducts. The addition of insulin to the
      combination of HGF and Wnt provided no growth or differentiation advantage. Our
      results indicate usefulness of Wnt and HGF in hepatocyte cultures and suggest
      their balance during normal liver development.

PMID- 14720516
TI  - Biochemical evidence for interaction between smoothelin and filamentous actin.
AB  - The two major isoforms of smoothelin (A and B) contain a calponin homology (CH)
      domain, colocalize with alpha-smooth muscle actin (alpha-SMA) in stress fibers
      and are only expressed in contractile smooth muscle cells (SMCs). Based on these
      findings, we hypothesized that smoothelins are involved in smooth muscle cell
      contraction, presumably via interaction with actin. The interaction between
      smoothelins and three different actin isoforms (alpha- and gamma-smooth muscle
      and alpha-skeletal actin [alpha-SKA]) was investigated using several in vitro
      assays. Smoothelin-B co-immunoprecipitated with alpha-smooth muscle actin from
      pig aorta extracts. In rat embryonic fibroblasts, transfected smoothelins-A and 
      B associated with stress fibers. In vitro dot blot assays, in which immobilized
      actin was overlaid with radio-labeled smoothelin, showed binding of smoothelin-A
      to actin filaments, but not to monomeric G-actin. A truncated smoothelin,
      containing the calponin homology domain, associated with stress fibers when
      transfected and bound to actin filaments in overlay, but to a lesser extent.
      ELISA results showed that the binding of smoothelin to actin has no significant
      isoform specificity. Our results indicate an interaction between smoothelin and
      actin filaments. Moreover, the calponin homology domain and its surrounding
      sequences appear to be sufficient to accomplish this interaction, although the
      presence of other domains is apparently necessary to facilitate and/or strengthen
      the binding to actin.

PMID- 14720517
TI  - A p53-independent pathway regulates nucleolar segregation and antigen
      translocation in response to DNA damage induced by UV irradiation.
AB  - The nucleolus is the site of ribosomal gene transcription, processing of rRNA
      transcripts and maturation of preribosomal particles. Recent studies have shown
      that nucleoli are also involved in processes as diverse as aging, proliferation
      control, stress response and mitotic regulation. The proliferation-dependent
      nucleolar antigen pKi-67 is a sensitive marker of both proliferative activity and
      nucleolar integrity. We show that staining for the nucleolar-associated antigen
      pKi-67 is lost from nucleoli during growth arrest following UV irradiation.
      Surprisingly, before cells enter growth arrest, Ki-67 staining translocates from
      nucleolar to nucleoplasmic sites within 4-6 h of irradiation. Ki-67
      redistribution is accompanied by segregation of nucleolar components. The timing
      of p53 response correlates well with pKi-67 translocation, growth arrest and
      restoration of proliferation. However, nucleolar segregation and pKi-67
      translocation occur in the absence of functional p53 and other components of
      damage response pathways (DNA-PK, CSA, CSB, XPA, XPC, ATM ATR, p38(MAPK) and
      MEK1). Neither gamma-irradiation nor H(2)O(2) treatment causes pKi-67
      translocation or loss of nucleolar integrity. In marked contrast, treatment of
      cells with UV-mimetic 4-NQO does induce nucleolar disruption and relocalisation
      of pKi-67, suggesting that bulky adduct formation in rDNA rather than strand
      breaks is sufficient to cause nucleolar segregation. Our data reveal a previously
      unrecognized cellular response to genotoxic stress and may reveal novel pathways
      leading to growth arrest.

PMID- 14720518
TI  - Myoblast migration is regulated by calpain through its involvement in cell
      attachment and cytoskeletal organization.
AB  - Cell migration is a fundamental cellular function particularly during skeletal
      muscle development. Ubiquitous calpains are well known to play a pivotal role
      during muscle differentiation, especially at the onset of fusion. In this study,
      the possible positive regulation of myoblast migration by calpains, a crucial
      step required to align myoblasts to permit them to fuse, was investigated.
      Inhibition of calpain activity by different pharmacological inhibitors argues for
      the involvement of these proteinases during the migration of myoblasts. Moreover,
      a clonal cell line that fourfold overexpresses calpastatin, the endogenous
      inhibitor of calpains, and that exhibits deficient calpain activities was
      obtained. The results showed that the migratory capacity of C2C12 and fusion into
      multinucleated myotubes were completely prevented in these clonal cells.
      Calpastatin-overexpressing myoblasts unable to migrate were characterized by
      rounded morphology, the loss of membrane extensions, the disorganization of
      stress fibers and exhibited a major defect in new adhesion formation.
      Surprisingly, the proteolytic patterns of desmin, talin, vinculin, focal adhesion
      kinase (FAK) and ezrin, radixin, moesin (ERM) proteins are the same in
      calpastatin-overexpressing myoblasts as compared to control cells. However, an
      important accumulation of myristoylated alanine-rich C kinase substrate (MARCKS)
      was observed in cells showing a reduced calpain activity, suggesting that the
      proteolysis of this actin-binding protein is calpain-dependent and could be
      involved in both myoblast adhesion and migration.

PMID- 14720519
TI  - EGF receptor transactivation by urokinase receptor stimulus through a mechanism
      involving Src and matrix metalloproteinases.
AB  - Urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor
      receptor (EGFR) are ubiquitous receptors involved in the control of a variety of
      cellular processes frequently found altered in cancer cells. The EGFR has been
      recently described to play a transduction role of uPAR stimuli, mediating uPA
      induced proliferation in highly malignant cells that overexpress uPAR. In the
      present work, we found for the first time that uPAR stimulation with the amino
      terminal fragment (ATF) of urokinase devoid of proteolytic activity
      transactivates the EGFR in mammary MCF-7 cells through a mechanism involving Src
      and a metalloproteinase, as indicated by its sensitivity to selected inhibitors.
      In these cells, which express low levels of uPAR and malignancy, both ATF and EGF
      stimuli induced an interaction of the EGFR with uPAR and ERK activation. However,
      EGFR activation by uPAR stimuli mediated cellular invasion rather than
      proliferation, while EGFR activation by EGF led to a proliferative response.
      These results revealed a complex modulation of EGFR function toward different
      cellular responses according to the status of uPAR activity. On the other hand,
      we also found that MMP-mediated activation of EGFR can occur in an autocrine
      manner in cells which secrete uPA. All this reveals novel regulatory systems
      operating through autocrine loops involving uPAR stimuli, Src, MMP and EGFR
      activation which could mediate fine control of physiological processes as well as
      contribute to the expression of proliferative and invasive phenotypes of
      cancerous cells.

PMID- 14720520
TI  - Transforming growth factor-beta activates both pro-apoptotic and survival signals
      in fetal rat hepatocytes.
AB  - Transforming growth factor-beta (TGF-beta) induces apoptosis in fetal rat
      hepatocytes. However, a subpopulation of these cells survives concomitant with
      changes in morphology and phenotype, reminiscent of an epithelial mesenchymal
      transition (EMT) [Exp. Cell Res. 252 (1999) 281-291]. In this work, we have
      isolated the subpopulation that survives to TGF-beta-induced apoptosis, showing
      that these cells maintain the response to TGF-beta in terms of Smads activation
      and growth inhibition. Analyses of the intracellular signals that could impair
      the apoptotic effects of TGF-beta have indicated that the phosphatidylinositol 3
      kinase (PI 3-K)/Akt pathway is activated in these resistant cells. Experiments in
      fetal rat hepatocytes have shown that TGF-beta is able to transiently activate PI
      3-K/Akt by a mechanism independent of protein synthesis but dependent on a
      tyrosine kinase activity. Pro-apoptotic signals, such as oxidative stress and
      caspases, contribute to the loss of Akt at later times. Inhibiting PI 3-K
      sensitizes fetal hepatocytes (FH) to the apoptosis induced by TGF-beta and causes
      spontaneous death in the resistant cells. In conclusion, TGF-beta, as it is known
      for other cytokines, could be inducing pro-apoptotic and survival signals in
      hepatocytes, the balance among them will decide cell fate.

PMID- 14720521
TI  - Altered distribution and co-localization of polycystin-2 with polycystin-1 in
      MDCK cells after wounding stress.
AB  - Polycystin-1 and -2 are integral membrane glycoproteins defective in autosomal
      dominant polycystic kidney disease (ADPKD). Recent studies showed a coupled
      polycystin-1 and -2 action in cell signaling and channel activation suggesting an
      important biological role for the two proteins at the plasma membrane. To gain a
      better understanding about the (co)-distribution and dynamics of the polycystin-1
      and -2 complex under stress conditions, we used a wound-healing model of Madine
      Darby canine kidney (MDCK) renal epithelial cells. In this model, cells near the
      wound edge undergo a process of reorganization to active migration, while cells
      further from the edge are unaffected and remain confluent. For the first time,
      endogenous polycystin-1 and -2 were found to partly co-localize in the plasma
      membrane of confluent monolayers, and both proteins co-localized in the primary
      cilium. Upon wound healing, the association of polycystin-2 to the membrane was
      greatly reduced at the wound edge and the submarginal cells. Polycystin-1
      remained incorporated to the membrane at the edge of the cell sheet at all time
      points, although strongly reduced in lamellipodia-forming cells. Adherens
      junctions and desmosomes, and respective connected actin and keratin cytoskeleton
      were also disturbed in lamellipodia-forming cells. We propose that altered
      subcellular localization of polycystin-1 and -2 as a result of stress will affect
      signaling and other cellular processes mediated by these proteins.

PMID- 14720522
TI  - Bacterial GroEL-like heat shock protein 60 protects epithelial cells from stress
      induced death through activation of ERK and inhibition of caspase 3.
AB  - Bacterial heat shock proteins (hsps) can have various effects on human cells. We
      investigated whether bacterial hsp60s can protect epithelial cells from cell
      death by affecting the mitogen-activated protein kinase (MAPK) signal pathways.
      Cell protection was studied by adding bacterial hsp60s to skin keratinocyte
      cultures (HaCaT cell line) before UV radiation. The results show that hsp60
      significantly protected against UV radiation-induced cell death. Effects of UV
      radiation and exogenous hsp60 on phosphorylation of MAPKs and on activation of
      caspase 3 were examined by Western blot analysis. UV radiation strongly induced
      phosphorylation of p38 MAPK and formation of active caspase 3. A p38 inhibitor,
      SB 203580, totally blocked UV radiation-mediated activation of caspase 3.
      Preincubation with hsp60 strongly induced phosphorylation of ERK1/2 and inhibited
      UV radiation-mediated activation of caspase 3. PD 98059, a specific inhibitor of
      the ERK1/2 pathway, blocked this inhibitory effect of exogenous hsp60. Studies on
      the association between activity of MAPKs or caspase 3 and cell death showed that
      the ERK1/2 pathway inhibitor reversed protective effect of hsp60 while specific
      inhibition of p38 and caspase 3 reduced cell death. These results indicate that
      in HaCaT cells UV radiation mediates cell death through activation of p38
      followed by caspase 3 activation. Exogenous hsp60 partially protects against UV
      radiation-mediated epithelial cell death through activation of ERK1/2, which
      inhibits caspase 3 activation.

PMID- 14720523
TI  - Progress with diabetic patients undergoing percutaneous coronary intervention.

PMID- 14720524
TI  - Sex differences: implications for heart failure care.

PMID- 14720525
TI  - Can sedentary patients with heart failure achieve the beneficial effect of
      exercise training without moving?

PMID- 14720526
TI  - Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients.
      Insights from the RAVEL Trial.
AB  - Patients with diabetes mellitus have less favourable outcomes after percutaneous
      coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis
      of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting
      stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238
      patients to treatment with either sirolimus-eluting or bare metal stents. Forty
      four patients were diabetic; 19 received sirolimus-eluting stents and 25 were
      treated with bare metal stents. The differences in outcomes between diabetic and
      non-diabetic patients treated with SES (n=101) were also assessed. Follow-up
      angiography was performed at 6 months. Major adverse cardiac events (MACE)
      defined as death, myocardial infarction (MI), or target lesion revascularization
      (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was
      significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs
      0.82+/-0.5mm; P<0.001) and similar to that in non-diabetics treated with SES (
      0.03+/-0.27mm). There was zero restenosis in the SES groups (diabetic and non
      diabetic) compared to a 42% rate in the diabetic population assigned to bare
      metal stents (P=0.001). After 12 months, there was one non-Q-wave MI and one non
      cardiac death in the diabetic SES group, while 12 patients in the bare metal
      stent group had MACE (one death, two MI, nine TLR) (P=0.01)-an event-free
      survival rate of 90% vs 52%, respectively (P<0.01). There were no TLRs in both
      SES groups compared to 36% rate in the diabetic bare metal stent group (P=0.007).
      Conclusion Diabetics treated with SES were associated with a virtual abolition of
      neointimal proliferation and low event rates at long-term follow-up.

PMID- 14720527
TI  - Admission Troponin T and measurement of ST-segment resolution at 60 min improve
      early risk stratification in ST-elevation myocardial infarction.
AB  - AIMS: The prognostic value of admission troponin T (tnT) levels and the
      resolution of the ST-segment elevation in ST-elevation myocardial infarction
      (STEMI) is well established. However, the combination of these two early
      available markers for predicting risk has not been evaluated. METHODS AND
      RESULTS: We evaluated 516 patients with fibrinolytic treated STEMI from the
      ASSENT-2 and ASSENT-PLUS studies, which had both admission tnT and ST-monitoring
      available. We used a prospectively defined cut-off value of tnT of 0.1microg/l.
      For ST-segment resolution, a cut-off of 50% measured after 60min was used. Both a
      tnT >/=0.1microg/l (n=116) and ST-segment resolution <50% (n=301) were related to
      higher one-year mortality, 13% vs 4% (P<0.001) and 8.4% vs 2.8% (P=0.009),
      respectively. In a multivariate analysis ST-segment resolution was and tnT showed
      a strong trend to be independently related to mortality. The combination of both
      further improved risk stratification. The one-year mortality in the group with
      elevation of tnT and without ST-segment resolution compared to the group without
      tnT elevation and with ST-segment resolution was 18.2% vs 2.8% (P<0.001).
      CONCLUSIONS: Both tnT on admission and ST-segment resolution after 60min are
      strong predictors of one-year mortality. The combination of both gives additive
      early information about prognosis and further improves risk stratification.

PMID- 14720528
TI  - Overweight and obesity in patients with established coronary heart disease: are
      we meeting the challenge?
AB  - AIMS: Several epidemiological studies have reported increasing obesity rates in
      the general population during last decades. We studied the prevalence of
      overweight and obesity in the high priority group of patients with established
      coronary heart disease (CHD) and the therapeutic control of manageable coronary
      risk factors in relation to body mass index. METHODS: Data from a representative
      sample of patients having experienced a recent cardiac event before the age of 71
      years from 15 European centres participating in the EUROASPIRE II study, were
      gathered in the period 1999-2000 through standardized methods. In total, 5535
      coronary patients with valid height and weight measurements were included.
      RESULTS: About one in three patients (31%) was diagnosed as obese with
      additionally half of the patient population being overweight (48%). Obesity was
      10% more prevalent among women and significantly less smokers were observed among
      overweight and obese subjects, twice as many diabetics and more people with low
      education. Overweight and obese patients had more frequently raised blood
      pressure and elevated cholesterol after adjustment for age, gender, education,
      diabetes and centre. In patients using blood pressure lowering agents, 56% of
      obese and 51% of overweight patients were still having raised blood pressure
      compared to 42% in normal weight patients. A similar result was observed for the
      therapeutic control of total cholesterol. Since their hospital discharge, obese
      and overweight patients did not alter lifestyles regarding fat intake and
      physical activity. In the period between coronary event and interview, body
      weight had increased with at least five kilograms in a quarter of all patients.
      CONCLUSIONS: These results suggest that the growing population of overweight and
      obese coronary patients is at particularly high risk for further cardiovascular
      complications due to elevated risk factor levels on the one hand and their
      insufficient therapeuticcontrol on the other hand. Our results also confirm the
      considerable weight gain seen in a high proportion of patients following their
      cardiac event.

PMID- 14720529
TI  - Female sex is associated with a better long-term survival in patients
      hospitalized with congestive heart failure.
AB  - AIMS: Results of previous studies on the influence of gender on prognosis in
      heart failure have been conflicting and most studies have been conducted in
      selected populations. The aim of this study was determine whether mortality risk
      in women and men hospitalized with congestive heart failure is different. METHODS
      AND RESULTS: Survival analysis of 5491 consecutive patients admitted with
      congestive heart failure to 34 Danish hospitals between 1993-1996. Follow-up time
      was 5-8 years. Forty percent of the patients were female. Females were older, had
      less evidence of ischaemic heart disease and their left ventricular systolic
      function was preserved to a greater extent than in males. Men were more often
      treated with ACE inhibitors. During the follow-up period 1569 women (72%) and
      2386 (72%) of the men died. When the age difference between men and women was
      adjusted for, male gender was associated with an increased risk of death (RR 1.25
      (1.17-1.34)) and the increased risk was confirmed in a multivariate model
      containing several covariates. CONCLUSIONS: In patients hospitalized with
      congestive heart failure male gender is an independent predictor of mortality.
      Female heart failure patients may be under-treated with ACE inhibitors.

PMID- 14720530
TI  - Beneficial effects of chronic low-frequency stimulation of thigh muscles in
      patients with advanced chronic heart failure.
AB  - AIMS: Patients with chronic heart failure (CHF) exhibit detrimental changes in
      skeletal muscle that contribute to their impaired physical performance. This
      study investigates the possibility of counteracting these changes by chronic low
      frequency electrical stimulation (CLFS) of left and right thigh muscles. METHODS
      AND RESULTS: (mean+/-SD) 32 CHF patients (53+/-10 years) with an LVEF of 22+/-5%,
      NYHA II-IV, undergoing optimized drug therapy, were randomized in a CLFS group
      (CLFSG) or a control group (controls). The groups differed in terms of the
      intensity of stimulation, which elicited strong muscle contractions only in the
      CLFSG, whereas the controls received current input up to the sensory threshold
      without muscle contractions. Functional capacity was assessed by peak VO(2), work
      capacity, and a 6-min-walk (6-MW). Muscle biopsies were analyzed for myosin heavy
      chain (MHC) isoforms, citrate synthase (CS) and glyceraldehydephosphate
      dehydrogenase (GAPDH) activities. Peak VO(2)(mlmin(-1)kg -1) increased from 9.6+/
      3.5 to 11.6+/-2.8 (P<0.001) in the CLFSG, and decreased from 10.6+/-2.8 to 9.4+/
      3.2 (P<0.05) in the controls. The increase in the CLFSG was paralleled by
      increases in maximal workload (P<0.05) and oxygen uptake at the anaerobic
      threshold (P<0.01). The corresponding values of the controls were unchanged, as
      also the 6-MW values, the MHC isoform distribution, and both CS and GAPDH
      activities. In the CLFSG, the 6-MW values increased (P<0.001), CS activity was
      elevated (P<0.05), GAPDH activity decreased (P<0.01), and the MHC isoforms were
      shifted in the slow direction with increases in MHCI at the expense of MHCIId/x
      (P<0.01). CONCLUSIONS: Our results suggest that CLFS is a suitable treatment to
      counteract detrimental changes in skeletal muscle and to increase exercise
      capacity in patients with severe CHF.

PMID- 14720531
TI  - A randomized placebo-controlled trial of pre-treatment and short- or long-term
      maintenance therapy with amiodarone supporting DC cardioversion for persistent
      atrial fibrillation.
AB  - AIMS: The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR)
      in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse
      may be reduced by amiodarone but no placebo-controlled trials of efficacy have
      been performed and the appropriate duration of therapy is unknown. METHODS AND
      RESULTS: In this double-blind study, 161 subjects with persistent AF were
      randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks
      prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62,
      short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52
      weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before
      DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on
      placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%,
      P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained
      in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%,
      P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR
      compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31
      to 2%, P=0.085). There was no difference in adverse event rate or quality of life
      scores between groups. CONCLUSIONS: Amiodarone pre-treatment before electrical
      DCCV for persistent AF allows chemical conversion in one-fifth of patients
      without altering the efficacy of subsequent DC conversion. Amiodarone is more
      effective than placebo in the maintenance of SR when continued for 8 weeks
      following successful DCCV. More patients taking long-term amiodarone remained in
      SR at 52 weeks, but more had serious adverse effects requiring discontinuation of
      therapy. Eight weeks of adjuvant therapy with amiodarone following successful
      DCCV may be the preferred option.

PMID- 14720532
TI  - Direct epicardial mapping predicts the recovery of left ventricular dysfunction
      in chronic ischaemic myocardium.
AB  - AIMS: This study investigated the hypothesis that direct epicardial bipolar
      mapping is able to predict the recovery of left ventricular (LV) dysfunction in
      ischaemic myocardium. METHODS AND RESULTS: In 34 patients with CAD, a maximum of
      102 bipolar epicardial electrograms per patient (n=3468 electrograms) were
      simultaneously recorded with a ventricular jacket array intraoperatively
      immediately prior to revascularization. Only LV electrograms with good myocardial
      contact (n=1813, 52+/-14 per patient, mean+/-SD) were analyzed. In accordance to
      the position of each electrode, segmental myocardial function was assessed by
      transthoracic echocardiography before and 7+/-2 months (mean+/-SD; range 3-10
      months) after CABG using a wall motion score. Preoperatively dysfunctional
      segments (n=700) were classified as viable (improvement in wall motion score of
      at least 20% following CABG, n=424) or non-viable (no improvement, n=276).
      Bipolar voltage was significantly lower in non-viable when compared to viable
      myocardium (P<0.001, ANOVA) At a cut-off value of 5.9mV, ROC-curve analysis for
      bipolar voltage (to discriminate between viable and non-viable myocardium)
      revealed a sensitivity of 83% at a specificity of 83% (area under the ROC-curve
      of 0.92+/-0.01, mean+/-SE). CONCLUSIONS: Direct epicardial mapping is able to
      predict the recovery of chronically ischaemic dysfunctional myocardium and
      thereby proves the presence of myocardial viability.

PMID- 14720533
TI  - Intravascular thermography: Immediate functional and morphological vascular
      findings.
AB  - AIMS: To investigate safety, feasibility, and injurious effect on endothelial
      cells of a thermography catheter as well as effect of flow on measured
      temperature in non-obstructive arteries. METHODS AND RESULTS: Safety and
      feasibility were tested in both rabbit aortas and pig coronary arteries.
      Evaluation of endothelial damage by the catheter (acute, 7 and 14 days) was
      performed in pig coronaries using Evans Blue, scanning electron microscopy (SEM)
      and Factor-VIII antibody and compared with normal arteries and arteries that
      underwent intravascular ultrasound (IVUS). The effect of flow on temperature
      heterogeneity was analysed both in vitro and in vivo conditions. All procedures
      were successful without any adverse events; intra- and inter-operator variability
      was low. Intracoronary use of the catheter was associated with acute but
      reversible de-endothelialization, paralleling the findings associated with IVUS
      use. Changes in flow velocities under physiologic flow conditions did not
      significantly influence the temperature differences measured both in vitro and in
      vivo; temperature heterogeneity was more pronounced in absence of flow.
      CONCLUSIONS: Intracoronary thermography using a dedicated catheter is safe and
      feasible with a similar degree of de-endothelialization as IVUS. Temperature
      heterogeneity remained unchanged under normal physiologic flow conditions
      allowing clinical use of thermography.

PMID- 14720534
TI  - Expert consensus document on the use of antiplatelet agents. The task force on
      the use of antiplatelet agents in patients with atherosclerotic cardiovascular
      disease of the European society of cardiology.

PMID- 14720535
TI  - Searching for dose-response in HF clinics.

PMID- 14720537
TI  - Growth hormone therapy, is it always good for the heart?

PMID- 14720538
TI  - Verapamil, atrial fibrillation recurrences and anticoagulation.

PMID- 14720539
TI  - Low cholesterol values are no longer common in China.

PMID- 14720540
TI  - Degradation of the textile dyes Basic yellow 28 and Reactive black 5 using
      diamond and metal alloys electrodes.
AB  - Basic yellow 28 (SLY) and Reactive black 5 (CBWB), which are respectively methine
      and sulfoazo textile dyes were individually exposed to electrochemical treatment
      using diamond-, aluminium-, copper- and iron-zinc alloy electrodes. The generated
      current was registered with time during electrolysis of the dye solutions and the
      color variation and the formation of degradation products were followed using
      HPLC with diode array detection. Four different electrodic materials were tested
      by applying different potentials in the range -1.0 to -2.5 V and presented 95%
      color removal and COD removal of up to 65-67% in the case of CBWB dye solution
      treated with the copper and iron electrodes. Efficiency was enhanced with
      stirring and flow in relation to the stationary regime. The kinetic parameter
      reaction rate was used to establish the effect of flow, potential, electrode
      nature and pH. The formation and characterization of the precipitate formed under
      certain conditions is reported and discussed.

PMID- 14720541
TI  - Al2O3-supported transition-metal oxide catalysts for catalytic incineration of
      toluene.
AB  - The catalytic incineration of toluene over gamma-Al2O3-supported transition-metal
      oxide catalysts in the temperature range of 200-380 degrees C was investigated
      employing a fixed bed flow reactor. CuO/gamma-Al2O3 was found to be the most
      active of seven catalysts tested. Using this catalyst with different wt% Cu in
      the incineration of toluene, we found that the optimal Cu content was 5 wt%. X
      ray diffraction, BET surface area and hydrogen-temperature-programmed reduction
      showed that it was mainly the formation of large CuO crystals that caused
      declines in catalyst activity at Cu content above 5 wt%. Addition of water vapor
      or CO2 inhibited catalyst activity, but this effect was reversible. Although
      coexistence of toluene and n-hexane resulted in a reduction in n-hexane
      conversion, the impact on toluene oxidation was only negligible. Temperature
      programmed desorption revealed that this differential effect was due to more
      competitive adsorption of toluene onto active sites of the catalyst.

PMID- 14720542
TI  - Photo-oxidation of cork manufacturing wastewater.
AB  - Several photo-activated processes have been investigated for oxidation of a cork
      manufacturing wastewater. A comparative activity study is made between different
      homogeneous (H2O2/UV-Vis and H2O2/Fe2+/UV-Vis) and heterogeneous (TiO2/UV-Vis and
      TiO2/H2O2/UV-Vis) systems, with degradation performances being evaluated in terms
      of total organic carbon (TOC) removal. Results obtained in a batch photo-reactor
      show that photo-catalysis with TiO2 is not suitable for this kind of wastewater
      while the H2O2/UV-Vis oxidation process, for which the effect of some operating
      conditions was investigated, allows to remove 39% of TOC after 4 h of operation
      (for C(H2O2)=0.59 M, pH=10 and T=35 degrees C). The combined photo-activated
      process, i.e., using both TiO2 and H2O2, yields an overall TOC decrease of 46%
      (for C(TiO2)=1.0 gl(-1)). The photo-Fenton process proved to be the most
      efficient, proceeds at a much higher oxidation rate and allows to achieve 66%
      mineralization in just 10 min of reaction time (for C(H2O2)=0.31 M, T=30 degrees
      C, Fe2+:H2O2=0.12 (mol) and pH=3.2).

PMID- 14720543
TI  - Haloalkane and haloacid dehalogenases from aerobic bacterial isolates indigenous
      to contaminated sites in Africa demonstrate diverse substrate specificities.
AB  - Five bacteria were isolated from contaminated sites in Nigeria and South Africa
      using the culture enrichment technique. They were subjected to standard cultural,
      biochemical and microbiological techniques and identified to be species of
      Bacillus, Burkholderia, Corynebacterium, Micrococcus and Pseudomonas. Axenic
      cultures of the bacterial isolates utilized 1,2-dichloroethane (1,2-DCE) as the
      sole carbon source up to a final substrate concentration of 10 mM. Their mean
      generation time in 1,2-DCE ranged significantly (P<0.05) from 9.77 to 15.72 h
      with the maximum chloride release ranging between 59% and 86%. All the bacterial
      isolates produced two different dehalogenases, viz. one which is heat labile and
      specific for halogenated alkanes with optimum activity at a pH of 7.5 and the
      other which is more heat stable with a higher pH optimum of 9.0 and specific for
      halogenated alkanoic acids. However, the two enzyme types when tested
      demonstrated wide substrate specificities. It is therefore adjudged that these
      organisms may play a vital role in the bioremediation of sites polluted with
      chlorinated hydrocarbons.

PMID- 14720544
TI  - Comparison of various advanced oxidation processes and chemical treatment methods
      for COD and color removal from a polyester and acetate fiber dyeing effluent.
AB  - In this paper, a comparison of various advanced oxidation processes (O3, O3/UV,
      H2O2/UV, O3/H2O2/UV, Fe2+/H2O2) and chemical treatment methods using
      Al2(SO4)3.18H2O, FeCl3 and FeSO4 for the chemical oxygen demand (COD) and color
      removal from a polyester and acetate fiber dyeing effluent is undertaken.
      Advanced oxidation processes (AOPs) showed a superior performance compared to
      conventional chemical treatment, which maximum achievable color and COD removal
      for the textile effluent used in this study was 50% and 60%, respectively.
      Although O3/H2O2/UV combination among other AOPs methods studied in this paper
      was found to give the best result (99% removal for COD and 96% removal for
      color), use of Fe2+/H2O2 seems to show a satisfactory COD and color removal
      performance and to be economically more viable choice for the acetate and
      polyester fiber dyeing effluent on the basis of 90% removal.

PMID- 14720545
TI  - Degradation of phenol and cresols at low temperatures using a suspended-carrier
      biofilm process.
AB  - Degradation of phenol and o-, m- and p-cresol at a concentration of 150 mg l(-1)
      of each compound was studied in a suspended-carrier biofilm process consisting of
      two aerobic stages. The fungus Mortierella sarnyensis Mil'ko dominated the
      microflora in the first reactor, while bacteria dominated in the second reactor.
      The process was studied at 4, 7, 11 and 15 degrees C. The results from the
      experiments showed the process to be relatively efficient even at 4 degrees C.
      The degradation rate was 33% of that at 15 degrees C for o-cresol. Both phenol
      and the cresols were degraded in the first reactor and a new peak appeared in the
      HPLC-chromatograms indicating the formation of one or more intermediate compounds
      in the first stage. These compounds were however degraded to below the detection
      limit in the second reactor. Small new peaks appeared in the chromatograms of the
      outlet from the second reactor at the maximum loading rates.

PMID- 14720546
TI  - Optimum conditions for Al13 polymer formation in PACl preparation by electrolysis
      process.
AB  - This paper introduces a new and effective method for preparation of PACl
      electrolysis process. A series of PACl with high content of Al13 polymer was
      successfully prepared by electrolysis process. The amount of Al13 polymer formed
      in electrolysis process was found to be highly influenced by current density
      (di), the distance between the electrodes, electrolysis time and the stirring
      rate of the electrolyte. For the AlT (total aluminum concentration) of 2.0 M PACl
      obtained by electrolysis process, the optimal di and distance between the
      electrodes were 1.1 Adm(-2) and 10 mm respectively. The optimum circulating rate
      was 5.5 l h(-1). Because of the inhomogeneous pH between the surface of cathode
      and the bulk solution, the electrolysis process has the advantage to form more
      Al(OH)4- as precursor of Al13 polymer. At the optimum condition, Al13 polymer
      accounted for above 70% of AlT (PACl of AlT=2.0 M and B=2.0), which was much
      higher than that of PACl prepared by other method.

PMID- 14720547
TI  - Adsorption of Cu and Mn on covalently cross-linked alginate gel beads.
AB  - The covalently cross-linked alginate gel beads were prepared by the reactions of
      Ca(2+)-doped alginate gel beads, which were formed by spraying a viscous alginate
      solution into a calcium chloride solution, with cyanogen bromide and following
      1,6-diaminohexane. The cross-linking of alginate matrix decreased the mean bead
      diameter by about 30% and made the beads durable in some extent under alkaline
      conditions. The adsorption of metal ions on the covalently cross-linked alginate
      gel beads was rapid and reached at equilibrium within 30 min at 25 degrees C.
      Adsorption isotherms of Cu(II), Mn(II), and Ca2+ on the beads possessed a
      stepwise shape, which was firstly determined by Rorrer et al. [Ind. Eng. Chem.
      Res. 32 (1993) 2170] for cross-linked chitosan gel beads and explained by a pore
      blockage mechanism. Higher selectivity was determined against Cu(II) over Mn(II)
      and Ca2+, especially at a low concentration region. These metal adsorption
      profiles for the covalently cross-linked alginate gel beads was almost the same
      as those for the un-cross-linked beads, indicating that the cross-linking
      reactions were performed without interfering the adsorption characteristics of
      alginate gel beads.

PMID- 14720548
TI  - Application of flotation for the separation of metal-loaded zeolites.
AB  - Several industrial wastewater streams may contain heavy metal ions, which must be
      effectively removed, before the discharge or reuse of treated waters could take
      place. Different bonding materials, presenting selectivity and fast reaction
      kinetics for the removal of metals, have been examined for this purpose. The
      objective of the present paper was to investigate the application of dispersed
      air flotation for the separation of metal-loaded sorbents. Two similar zeolite
      samples were applied as effective bonding agents for the removal of zinc, a toxic
      metal commonly found in many industrial wastewaters. This combined process,
      termed sorptive flotation, involves the preliminary scavenging of metal ions, by
      using the appropriate sorbent particles (usually present as ultrafine
      particulates), followed by flotation for the effective separation of them. The
      obtained results were very promising, as both metal and sorbent were effectively
      removed/separated from the dispersion.

PMID- 14720549
TI  - Chemical oxidative degradation of methyl tert-butyl ether in aqueous solution by
      Fenton's reagent.
AB  - Degradation of methyl tert-butyl ether (MTBE) in aqueous solution by Fenton's
      reagent (Fe2+ and H2O2) was investigated. Effects of reaction conditions on the
      oxidation efficiency of MTBE by Fenton's reagent were examined in batch
      experiments. Under optimum conditions, 15 mM H2O2, 2 mM Fe2+, pH 2.8 and room
      temperature, the initial 1 mM MTBE solution was reduced by 99% within 120 min.
      Results showed that MTBE was decomposed in a two-stage reaction. MTBE was first
      decomposed swiftly based on a Fe2+/H2O2 reaction and then decomposed somewhat
      less rapidly based on a Fe3+/H2O2 reaction. The detection of Fe2+ also supported
      the theory of the two-stage reaction for the oxidation of MTBE by Fenton's
      reagent. The dissolved oxygen in the solution decreased rapidly in the first
      stage reaction, but it showed a slow increase in the second stage with a zero
      order kinetics. A reaction mechanism involving two different pathways for the
      decomposition of MTBE by Fenton's reagent was also proposed. Chemicals including
      tert-butyl formate, tert-butyl alcohol, methyl acetate and acetone were
      identified to be the primary intermediates and by-products of the degradation
      processes.

PMID- 14720550
TI  - The fate of lindane in the conventional activated sludge treatment process.
AB  - A pilot-scale treatability study was performed to evaluate the fate of lindane
      (gamma-hexachlorocyclohexane) in wastewater treatment plants operating in the
      conventional activated sludge mode. Different types of wastewater (industrial and
      municipal) spiked with variable lindane concentrations were used at different
      dosing rates in order to determine distribution and removal under various
      operational conditions. The major amount (67-91%) of lindane inputs to the
      treatment process was found to concentrate in primary sludge. A significant
      linear correlation between the compound's partition coefficient (logKp) and the
      organic fraction of primary sludge (foc) was found. Sorption on primary sludge
      solids was concluded to be the major removal mechanism. Only 0.1-2.8% of lindane
      inputs was concentrated in activated sludge. Lindane losses in primary treatment
      were low (4-26%). Higher losses (up to 61%) were observed during the biological
      treatment probably due to biodegradation. These losses were negatively correlated
      with the inflow rate of lindane into the aeration tank. Activated sludge aged
      about 23 d presented the maximum loss of lindane. Increased sludge age was
      associated with increased percentages of lindane in the final effluent.

PMID- 14720551
TI  - An anaerobic continuous-flow fixed-bed reactor sustaining a 3-chlorobenzoate
      degrading denitrifying population utilizing versatile electron donors and
      acceptors.
AB  - An anaerobic continuous-flow fixed-bed column reactor capable of degrading 3
      chlorobenzoate (3-CBA) under denitrifying conditions was established, and its
      rate reached 2.26 mM d(-1). The denitrifying population completely degraded 3-CBA
      when supplied at 0.1-0.54 mM, but its activity was partly suppressed when 3-CBA
      was supplied at 0.89 mM. Nitrate was concomitantly consumed throughout the
      operation of the reactor, the amount of which was similar to or up to 35% higher
      than the theoretical stoichiometric value that was calculated by assuming that 3
      CBA degradation is coupled with denitrification. Batch incubation experiments
      proved that nitrate is strictly required for 3-CBA degradation in the absence of
      molecular oxygen. The population also degraded 3-CBA aerobically. Benzoate and 4
      CBA were degraded under denitrifying conditions as well as 3-CBA, but 2-CBA was
      not. Considering that the previously reported denitrifying 3-CBA-degrading
      cultures do not exhibit 4-CBA degradation under denitrifying conditions, nor
      aerobic 3-CBA degradation [FEMS Microbiol. Lett. 144 (1996) 213, Appl. Environ.
      Microbiol. 66 (2000) 3446], the microbial population developed in this experiment
      was physiologically versatile with respect to the utilization of both electron
      donors and electron acceptors.

PMID- 14720552
TI  - Bioleaching of heavy metals from anaerobically digested sewage sludge using FeS2
      as an energy source.
AB  - The effect of using FeS2 as an energy source, on the bioleaching of heavy metals
      (Zn, Cr, Cu, Pb and Ni) and nutrients (nitrogen and phosphorus) from
      anaerobically digested sludge using isolated indigenous iron-oxidizing bacteria
      was investigated in this paper. Addition of FeS2 in the range of 0.5-4.0 g l(-1)
      accelerated the acidification of sludge and raised the oxidation-reduction
      potential of sludge medium with an inoculation of 15% (v/v) of active bacteria,
      thus resulting in an overall increase in metal dissolution efficiency. After 16
      days of bioleaching at 28 degrees C and an initial pH of 3.0, up to 99% of Zn,
      65% of Cr, 74% of Cu, 58% of Pb and 84% of Ni can be removed from the sludge. In
      contrast, only 94% of Zn, 12% of Cr, 21% of Cu, 32% of Pb and 38% of Ni were
      leached out in the control without inoculation of iron-oxidizing bacteria and the
      addition of FeS2. Less than 15% of nitrogen and 6% of phosphorous were lost after
      16 days of bioleaching when using FeS2 as the energy source. Comparing to 39% and
      45% loss respectively for these two nutrients when using FeSO4.7H2O as the energy
      source, FeS2 appears to be a more suitable energy source for preserving nutrients
      in sludge while removing heavy metals from sludge.

PMID- 14720553
TI  - Microbial kinetic analysis of three different types of EBNR process.
AB  - The disadvantages of developed biological nutrient removal (BNR) processes
      (additional energy for liquid circulation and addition of external carbon
      substrate for denitrification in anoxic zones) were improved by reconfiguring the
      process into (1) an anaerobic zone followed by multiple stages of aerobic-anoxic
      zones (TNCU3 process) or (2) anaerobic, oxic, anoxic, oxic zones in sequence
      (TNCU2 process). These two pilot plants were operated at a recycling sludge ratio
      of 0.5 without internal recycle of nitrified supernatant. The sludge retention
      time was maintained at 10 d. The main objective of this study is to analyze the
      kinetics of different microorganisms in these two processes and A2O process by
      using the Activated Sludge Model No. 2d. The effective removal efficiency of
      carbon, total phosphorus and total nitrogen at 87-98%, 92-100% and 63-80%,
      respectively, were achieved in the testing runs. According to model simulations,
      the microbial kinetics in the TNCU3 and TNCU2 processes would be affected by
      different operations. When the step feeding strategy was adopted, the HRT was
      longer due to the less influent flowrate in the front stages and the microbes
      would grow in quantities by about 6% in the aerobic reactors. In the followed
      anoxic reactors, the microbes would decrease in quantities by about 12% due to
      the dilution effect. The dilution effects in TNCU3 and TNCU2 processes did not
      take place in A2O process because the recycling mixed liquid from the aerobic
      reactor to the anoxic reactor still contained particulate components. The XH,
      XPAO, and XAUT concentrations in the effluent of the last tank were lower when
      the step-feeding mode was adopted. The TNCU3 and TNCU2 processes could be
      operated efficiently without nitrified liquid circulation and addition of
      external carbon substrate for denitrification.

PMID- 14720554
TI  - A batch kinetic study on decolorization and inhibition of Reactive Black 5 and
      Direct Brown 2 in an anaerobic mixed culture.
AB  - Decolorization and inhibition kinetic characteristics of two azo dyes namely
      Reactive Black 5 (RB 5) and Direct Brown 2 (DB 2) were investigated with
      partially granulated anaerobic mixed culture using glucose (3000 mg l(-1) COD) as
      carbon source and electron donor during batch incubation. Monod, zero-, first-,
      and second-order reaction kinetic models were tested in order to determine the
      most suitable rate model of substrate and color removal kinetic. The course of
      the decolorization and substrate removal process approximates to first-order
      kinetic model under batch conditions. Decolorization, and substrate removal were
      achieved effectively under test conditions but ultimate removal of azo dyes and
      substrate were not observed at high dye concentrations. Aromatic amine and
      volatile fatty acid accumulation were observed proportionally at a higher azo dye
      concentration. A competitive kinetic model that describes the anaerobic co
      metabolism of increasing RB 5 and DB 2 dye concentrations with glucose as co
      substrate has been developed based on the experimental data.

PMID- 14720555
TI  - Photodestruction of Acid Orange 7 (AO7) in aqueous solutions by UV/H2O2:
      influence of operational parameters.
AB  - The photodestruction of Acid Orange 7 (AO7), an anionic acidic dye, was studied
      in the UV/H2O2 process. H2O2 and UV light have a negligible effect when they were
      used on their own. Removal efficiency of AO7 was sensitive to the operational
      parameters such as initial H2O2 concentration, initial AO7 concentration, pH and
      different light sources. The photodestruction of AO7 was inhibited by addition of
      EtOH as an electron scavenger. The semi-logarithmic graphs of the concentration
      of AO7 versus time (t<30 min) were linear, suggesting pseudo-first order
      reactions (k(optimum)=0.105 min(-1)). A simple kinetic model is proposed which is
      in agreement with experimental results.

PMID- 14720556
TI  - Preparation of alginate-chitosan hybrid gel beads and adsorption of divalent
      metal ions.
AB  - Naturally occurring polysaccharides such as alginic acid and chitosan have been
      recognized as one of the most effective adsorbents to eliminating low levels of
      heavy metal ions from waste water stream. The present study intended to use
      alginic acid and chitosan simultaneously, which are expected to form a rigid
      matrix structure of beads due to electrostatic interaction between carboxyl
      groups on alginic acid and amino groups on chitosan, and to prepare alginate
      chitosan hybrid gel beads. This could be achieved for the first time by using
      water-soluble chitosan, which was obtained by deacetylating chitin to 36-39%
      degree. The water-soluble chitosan dissolved in water could remain in solution in
      the presence of sodium alginate, and the homogeneous solution of chitosan and
      alginate was dispensed into a CuCl2 solution to give gel bead particles. The
      resultant beads were then reinforced by a cross-linking reaction of aldehyde
      groups on glutaraldehyde with amine groups on the chitosan. The cross-linking
      reaction made the beads durable under acidic conditions. The adsorption of
      Cu(II), Co(II), and Cd(II) on the beads was significantly rapid and reached at
      equilibrium within 10 min at 25 degrees C. Adsorption isotherms of the metal ions
      on the beads exhibited Freundlich and/or Langmuir behavior, contrary to gel beads
      either of alginate or chitosan showing a step-wise shape of adsorption isotherm.

PMID- 14720557
TI  - The ability of Azolla caroliniana to remove heavy metals (Hg(II), Cr(III),
      Cr(VI)) from municipal waste water.
AB  - The aim of this paper was to investigate the capacity of a small water fern,
      Azolla caroliniana Willd. (Azollaceae), to purify waters polluted by Hg and Cr.
      Many plants are capable of accumulating heavy metals (called hyperaccumulators)
      and one of them is the water fern A. caroliniana. During 12 days of the
      experiment the fern was grown on the nutrient solution containing Hg2+, Cr3+ and
      CrO4(2-) ions, each in a concentration 0.1, 0.5 and 1.0 mg dm(-3). The presence
      of these ions caused a 20-31% inhibition of A. caroliniana growth, the highest in
      the presence of Hg(II) ions, in comparison to the control. After day 12 of the
      experiment, metal contents the solution decreased to 0-0.25 mg dm(-3), and this
      decrease comprised between 74 (Cr3+ 1.0 mg dm(-3) treatment) and 100% (CrO4(2-)
      0.1 mg dm(-3) treatment). The fern took a lesser quantity of the metals from 0.1
      mg dm(-3) treatments compared to 0.5 and 1.0 mg dm(-3) treatments. In the A.
      caroliniana tissues the concentration of heavy metals under investigation ranged
      from 71 to 964 mg kg(-1) dm; the highest level being found for Cr(III) containing
      nutrient solution.

PMID- 14720558
TI  - Covering the parts other Bioshields don't reach.

PMID- 14720559
TI  - Nucleic acid amplification tests for diagnosis of tuberculous meningitis.

PMID- 14720560
TI  - Nucleic acid amplification tests for diagnosis of tuberculous meningitis.

PMID- 14720562
TI  - The European Commission pocket CDC: encore un effort!

PMID- 14720564
TI  - Human monkeypox: an emerging zoonosis.
AB  - Human monkeypox is a rare viral zoonosis endemic to central and western Africa
      that has recently emerged in the USA. Laboratory diagnosis is important because
      the virus can cause disease that is clinically indistinguishable from other pox
      like illnesses, particularly smallpox and chickenpox. Although the natural animal
      reservoir of the monkeypox virus is unknown, rodents are the probable source of
      its introduction into the USA. A clear understanding of the virulence and
      transmissibility of human monkeypox has been limited by inconsistencies in
      epidemiological investigations. Monkeypox is the most important orthopoxvirus
      infection in human beings since the eradication of smallpox in the 1970s. There
      is currently no proven treatment for human monkeypox, and questions about its
      potential as an agent of bioterrorism persist.

PMID- 14720565
TI  - What does epidemiology tell us about risk factors for herpes zoster?
AB  - Reactivation of latent varicella zoster virus as herpes zoster is thought to
      result from waning of specific cell-mediated immunity, but little is known about
      its determinants in individuals with no underlying immunosuppression. We
      systematically reviewed studies of zoster epidemiology in adults and analysed
      data from a large morbidity study to identify factors that might be modulated to
      reduce the risk of zoster. Annual zoster incidence in population-based studies
      varied from 3.6-14.2/10(3) in the oldest individuals. Risk factors identified in
      analytical studies that could explain this variation included age, sex,
      ethnicity, genetic susceptibility, exogenous boosting of immunity from varicella
      contacts, underlying cell-mediated immune disorders, mechanical trauma,
      psychological stress, and immunotoxin exposure. Our review highlights the lack of
      information about risk factors for zoster. We suggest areas of research that
      could lead to interventions to limit the incidence of zoster. Such research might
      also help to identify risk factors for age-related immune decline.

PMID- 14720566
TI  - The changing face of malignant (necrotising) external otitis: clinical,
      radiological, and anatomic correlations.
AB  - Malignant (necrotising) external otitis is an invasive infection of the external
      auditory canal. Although elderly patients with diabetes remain the population
      most commonly affected, immunosuppressed individuals (eg, from HIV infection,
      chemotherapy, etc) are also susceptible to malignant external otitis. Pseudomonas
      aeruginosa is isolated from the aural drainage in more than 90% of cases. The
      pathophysiology is incompletely understood although aural water exposure (eg,
      irrigation for cerumen impaction) has been reported as a potential iatrogenic
      factor. The typical patient presents with exquisitely painful otorrhoea. If
      untreated, cranial neuropathies (most commonly of the facial nerve) can develop
      due to subtemporal extension of the infection. The diagnosis of malignant
      external otitis is based on a combination of clinical findings, an increased
      erythrocyte sedimentation rate, and radiographic evidence of soft tissue with or
      without bone erosion in the external canal and infratemporal fossa. Treatment
      consists of prolonged administration (6-8 weeks) of an antipseudomonal agent
      (typically an orally administered quinolone). With the introduction and
      widespread use of both oral and topical quinolones, there are reports of less
      severe presentation of malignant external otitis and even the emergence of
      ciprofloxacin resistance. Reservation of systemic quinolones for the treatment of
      invasive ear infections is recommended.

PMID- 14720567
TI  - T helper cells and efficacy of Haemophilus influenzae type b conjugate
      vaccination.
AB  - A small number of fully vaccinated children in the UK have experienced invasive
      Haemophilus influenzae type b (Hib) infection. A rise in disease in recent years
      has been associated with lower vaccine-induced antibody levels over the first 5
      years of life, forcing greater dependence on immunological memory for protection.
      This has necessitated the introduction of a catch-up campaign, designed to boost
      immunity in children aged 6 months to 4 years of age. We suggest that the
      conjugate vaccine's inability to induce pathogen specific helper T cells,
      combined with a loss of natural boosting due to reduced circulation of Hib, may
      have contributed to the rising incidence of invasive disease 10 years after
      introduction of the conjugate vaccine. If so, the changing epidemiology of Hib
      infection in the UK may in part reflect the failure of a subunit vaccine to
      activate adequately all the necessary components of the immune system. This
      observation has implications for optimal scheduling of more recently licensed
      meningococcal and pneumococcal conjugate vaccines.

PMID- 14720568
TI  - Educational interventions to improve antibiotic use in the community: report from
      the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002.
AB  - National and international strategies for the control of antibiotic resistance
      recommend education for health-care professionals and the public to promote
      prudent antibiotic use. This paper, based on discussions at the 2002 colloquium
      of the International Forum on Antibiotic Resistance (IFAR), provides an
      international discourse between theoretical approaches to behaviour change and
      practical experience gained in large-scale antibiotic use educational campaigns.
      Interventions are more likely to be effective if their aim is to change
      behaviour, rather than provide information. They should target all relevant
      groups, especially parents, children, day-care staff, and health-care
      professionals. They should use clear and consistent messages concerning bacterial
      versus viral infection, prudent antibiotic use, symptomatic treatment, and
      infection-control measures (eg, handwashing). Campaigns should use a range of
      communications using pilot-testing, strong branding, and sociocultural
      adaptation. Prime-time television is likely to be the most effective public
      medium, while academic detailing is especially useful for health-care
      professionals. Multifaceted interventions can improve antibiotic prescribing to
      some degree. However, there are few data on their effects on resistance patterns
      and patient outcomes, and on their cost-effectiveness. Current research aims
      include the application of behaviour-change models, the development and
      validation of prudent antibiotic prescribing standards, and the refinement of
      tools to assess educational interventions.

PMID- 14720569
TI  - A rare case of oral leishmaniasis.

PMID- 14720570
TI  - Alasdair Geddes--Emeritus Professor of Infection in the School of Medicine,
      University of Birmingham, UK. Interview by Pam Das.

PMID- 14720571
TI  - Laryngeal tuberculosis.

PMID- 14720576
TI  - Unfit for animal consumption.

PMID- 14720577
TI  - VEGF and ALS: the luckiest growth factor?

PMID- 14720579
TI  - P-selectin modulation in haemostasis: one size fits all?

PMID- 14720578
TI  - TGF-beta, T-cell tolerance and anti-CD3 therapy.

PMID- 14720580
TI  - Inhibition of anandamide hydrolysis: cells also know how to do it.

PMID- 14720581
TI  - IDO and tolerance to tumors.

PMID- 14720582
TI  - Molecular mechanisms of the modulatory effects of HCMV infection in tumor cell
      biology.

PMID- 14720583
TI  - Molecular oncology in the post-genomic era: the challenge of proteomics.

PMID- 14720584
TI  - The GPIbalpha-thrombin interaction: far from crystal clear.

PMID- 14720585
TI  - The K/BxN mouse: a model of human inflammatory arthritis.

PMID- 14720586
TI  - An aromatase inhibitor or high water temperature induce oocyte apoptosis and
      depletion of P450 aromatase activity in the gonads of genetic female zebrafish
      during sex-reversal.
AB  - Dietary administration of a cytochrome P450 aromatase (P450arom) inhibitor
      (fadrozole) in genetic female juveniles of zebrafish (Danio rerio) was performed
      at 15-40 days post-hatching. The percentage of gonadal masculinization in the
      genetic all-females at 40 days post-hatching, treated with 0, 10, 100 and 1000
      microg fadrozole g(-1) diet(-1) were 0, 62.5, 100 and 100%, respectively. Rearing
      at high water temperature in genetic all-females was performed at 15-25 days post
      hatching. The percentage of gonadal masculinization in the genetic all-females at
      40 days post-hatching, at water temperatures of 28.5, 35 and 37 degrees C were 0,
      68.8 and 100%, respectively. Terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling (TUNEL)-positive oocytes of early diplotene and perinucleolar
      stages in fadrozole-treated genetic females (1000 microg g(-1) diet(-1)) were
      observed at 15-40 days post-hatching during sex-reversal. In contrast, apoptotic
      oocytes of early diplotene stage in high temperature-treated genetic females (at
      35 and 37 degrees C) during sex-reversal and presumptive males of wild-type fish
      during sex differentiation were found at 15-27 days post-hatching. Our findings
      indicate that oocyte apoptosis, depletion of P450arom activity and
      differentiation of spermatogonia during gonadal sex-reversal are caused by
      treatments of aromatase inhibitor or high water temperature.

PMID- 14720587
TI  - Vasodilator mechanisms in the dorsal aorta of the giant shovelnose ray,
      Rhinobatus typus (Rajiformes; Rhinobatidae).
AB  - This study investigated the nature of vasodilator mechanisms in the dorsal aorta
      of the giant shovelnose ray, Rhinobatus typus. Anatomical techniques found no
      evidence for an endothelial nitric oxide synthase, but neural nitric oxide
      synthase was found to be present in the perivascular nerve fibres of the dorsal
      aorta and other arteries and veins using both NADPH-diaphorase staining and
      immunohistochemistry with a specific neural NOS antibody. Arteries and veins both
      contained large nNOS-positive nerve trunks from which smaller nNOS-positive
      bundles branched and formed a plexus in the vessel wall. Single, varicose nNOS
      positive nerve fibres were present in both arteries and veins. Within the large
      bundles of both arteries and veins, groups of nNOS-positive cell bodies forming
      microganglia were observed. Double-labelling immunohistochemistry using an
      antibody to tyrosine hydroxylase showed that nearly all the NOS nerves were not
      sympathetic. Acetylcholine always caused constriction of isolated rings of the
      dorsal aorta and the nitric oxide donor, sodium nitroprusside, did not mediate
      any dilation. Addition of nicotine (3 x 10(-4) M) to preconstricted rings caused
      a vasodilation that was not affected by the nitric oxide synthase inhibitor, L
      NNA (10(-4) M), nor the soluble guanylyl cyclase inhibitor, ODQ (10(-5) M). This
      nicotine-mediated vasodilation was, therefore, not due to the synthesis and
      release of NO. Disruption of the endothelium significantly reduced or eliminated
      the nicotine-mediated vasodilation. In addition, indomethacin (10(-5) M), an
      inhibitor of cyclooxygenases, significantly increased the time period to maximal
      dilation and reduced, but did not completely inhibit the nicotine-mediated
      vasodilation. These data support the hypothesis that a prostaglandin is released
      from the vascular endothelium of a batoid ray, as has been described previously
      in other groups of fishes. The function of the nitrergic innervation of the blood
      vessels is not known because nitric oxide does not appear to regulate vascular
      tone.

PMID- 14720588
TI  - Interplay between metabolic rate and diet quality in the South American fox,
      Pseudalopex culpaeus.
AB  - We studied the metabolic costs associated with the ingestion of peppertree fruits
      (Schinus molle) in the culpeo fox, Pseudalopex culpaeus, the second largest canid
      in South America. Throughout its range of distribution, this fox feeds on rodents
      and other small vertebrates, and also on peppertree fruits, which represent 98%
      of total fruits consumed in semiarid Chile. Peppertree contains a high diversity
      of phytochemicals. Foxes feeding on diets containing rats and peppertree fruits
      (mixed diets) exhibited a 98.9% increase in basal rate of metabolism when
      compared to rat-acclimated foxes. Thus, acute ingestion of chemically defended
      fruits has an energetic cost for the fox, reflected in higher values of basal
      metabolism. Increased metabolic rates may be associated with increased protein
      synthesis for detoxification and for tissue repair, including the production of
      biotransformation enzymes.

PMID- 14720589
TI  - Developmental regulation of catecholamine levels during sea urchin embryo
      morphogenesis.
AB  - Results of a number of pharmacological studies suggest that catecholamines play a
      regulatory role in cleavage, morphogenesis and cell differentiation during early
      animal embryonic development. Few studies, however, have actually assayed for
      levels of catecholamines in these early embryos by methods that are both
      sensitive and specific. In this investigation the catecholamines dopamine,
      norepinephrine and epinephrine and their precursor, dopa and metabolites were
      determined in eight different embryonic stages of the sea urchin, Lytechinus
      pictus from hatched blastula to late pluteus larva, using high performance liquid
      chromatography with electrochemical detection. Levels of each of the
      catecholamines exhibited unique developmental profiles and are consistent with a
      role for epinephrine in blastula and early gastrula embryos and for
      norepinephrine in gastrulation. Changes in levels of catecholamine precursor and
      metabolites suggest a changing pattern of synthetic and metabolic enzyme
      activity, which can, for the most part, explain the fluctuations in catecholamine
      levels during development from blastula to the pluteus larva stage.

PMID- 14720590
TI  - Net uptake of chloride across the posterior gills of the Chinese crab (Eriocheir
      sinensis).
AB  - Two methods are commonly used for the determination of transbranchial net fluxes
      of Na+ and Cl-: direct analysis of changes in ion concentrations in the external
      medium using flame spectrophotometry or titration (net flux method), and
      measurement of unidirectional ion fluxes by means of radioactive tracers (tracer
      method). When we applied both methods in the same preparation, the isolated
      perfused posterior gill of freshwater-acclimated Eriocheir sinensis, to determine
      net fluxes of Cl-, the results differed substantially. In artificial fresh water
      (AFW) containing NaCl, the net flux method yielded a net uptake, but the tracer
      method showed a net efflux of Cl-. The net uptake of Cl- was abolished in Na(+)
      free AFW indicating that Cl- uptake is coupled with the uptake of Na+. Applying
      the tracer method, net efflux of Cl- remained almost unchanged in Na(+)-free AFW.
      This suggests the opposite mechanism, i.e. uncoupled uptake of Na+ and Cl-. The
      discrepancy in the results obviously depends on the method employed. Since the
      data obtained with the net flux method explain the osmoregulatory performance of
      crabs living in fresh water, we consider this method as appropriate for
      determining net transbranchial ion fluxes.

PMID- 14720591
TI  - Blood glucose concentration in caviomorph rodents.
AB  - Hystricomorph rodents are a group of species that belong to the suborder
      Hystricognathi. They mainly inhabit South American (caviomorph) and African
      (phiomorph) habitats. This group of rodents has a divergent insulin structure.
      For example, insulin in this group of rodents exhibits only 1-10% of biological
      activity in comparison to other mammals. Therefore, hystricomorph rodents may
      hypothetically be unable to regulate blood glucose concentration as non
      hystricomorph mammals. In this work we evaluated blood glucose concentration in
      nine species of caviomorph rodents, with emphasis on species belonging to the
      families Abrocomidae, Ctenomyidae and Octodontidae. Specifically we: (1) measured
      glucose concentrations after a fasting period; and (2) conducted a glucose
      tolerance test. In the latter assay we used Octodon degus as a representative
      species of the genus Octodon. Results showed that blood glucose concentration
      values after fasting, and in the glucose tolerance test, were within the expected
      range for mammals. We postulate that this group of rodents has compensatory
      traits that may permit the maintenance of standard values of plasma glucose.

PMID- 14720592
TI  - Development of cholinergic chronotropic control in chick (Gallus gallus
      domesticus) embryos.
AB  - In chick (Gallus gallus domesticus) embryos, instantaneous heart rate begins to
      fluctuate with the appearance of rapid, transient decelerations at around the end
      of the second week of incubation. Previously, it was shown that instantaneous
      heart rate decelerations were eliminated by administration of atropine and
      concurrently heart rate baseline was elevated in late embryos. Because the
      previous study lacked statistical treatment and there has been recent controversy
      over the development of tonic vagal control of the heart, we reexamine the
      hypothesis that transient decelerations of instantaneous heart rate are mediated
      by vagus nerve and the vagal tone begins to appear at around the end of the
      second week of incubation. Atropine administration tests were conducted for sixty
      seven 11- to 14-day-old and 18-day-old embryos in total. Heart rate decelerations
      appeared sporadically in three out of ten 12-day-old embryos, but the difference
      of mode heart rate before and after administration of atropine was not
      significant. Seven out of nine 13-day-old embryos and all nine 14-day-old embryos
      showed heart rate decelerations and the difference of mode heart rate before and
      after atropine administration was significant. In late (18-day-old) embryos,
      magnitude and frequency of instantaneous heart rate decelerations further
      increased with additional appearance of transient, irregular accelerations.
      Administration of varying doses of atropine completely eliminated the heart rate
      decelerations and elevated the heart rate baseline more markedly than in young
      embryos, indicating the maturation of vagal tone late in incubation.

PMID- 14720593
TI  - Protein growth rate in rainbow trout (Oncorhynchus mykiss) is negatively
      correlated to liver 20S proteasome activity.
AB  - The efficiency with which fish and other animals add and maintain body proteins
      is a balance between synthesis of proteins and their degradation. In fish that
      have similar food consumption and protein synthesis rates, a greater ratio of
      synthesis to degradation would be expected to produce more efficient conversion
      of food into growth. In addition, we hypothesised that high activities of the
      proteasome, a major pathway of protein degradation, would be negatively
      correlated with growth rate. In order to test this hypothesis we maintained
      rainbow trout for 62 days, during which repeat measurements of food consumption
      and growth were made. We selected fish for high and low growth efficiencies.
      Protein degradation was estimated from the difference between protein synthesis
      (determined by 15N flux) and protein growth. We found that protein synthesis
      rates were significantly higher in the low growth efficiency group, as were
      estimated protein degradation rates. In another group of fish that also did not
      differ in food consumption, the activity of the proteasome in the liver, but not
      in the muscle, was negatively correlated with growth rates. These two experiments
      showed that high proteasome activity is linked to decreased growth efficiency.

PMID- 14720594
TI  - Biochemical properties and immunohistochemical localization of carbonic anhydrase
      in the sacculus of the inner ear in the salmon Oncorhynchus masou.
AB  - Carbonic anhydrase (CA) in the inner ear sacculus was examined by activity assay,
      Western blotting and immunohistochemistry to determine its role in otolith
      calcification. An immunoreactive protein with a molecular mass of approximately
      28 kDa was detected by Western blotting. The CO2 hydration activity in the
      cytosol fraction of the sacculus was 5.4 units/mg protein, while little or no
      activity was detected in the nuclear and mitochondrial fractions. The enzyme
      activity was highly inhibited by acetazolamide. The concentration of 50%
      inhibition was 8.16 nM and the inhibition constant of the activity was 8.25 nM.
      Transitional and squamous epithelial cells of the sacculus were immunopositive
      with an anti-CA II antibody, but sensory epithelial cells and mitochondria-rich
      cells in the transitional epithelium were not. These results suggest that
      transitional epithelial cells other than mitochondria-rich cells and squamous
      epithelial cells play an important role in otolith calcification by supplying
      bicarbonate to otoliths and/or by eliminating protons from endolymph.

PMID- 14720595
TI  - No latitudinal differences in adrenocortical stress response in wintering black
      capped chickadees (Poecile atricapilla).
AB  - Birds respond to deterioration in environmental conditions by elevating their
      corticosterone levels, which can enhance their survival. It is less clear if
      animals constantly living in energetically challenging environment show similar
      increases in adrenocortical function. Previous work has demonstrated that under
      controlled conditions black-capped chickadees (Poecile atricapilla) from northern
      latitudes cache more food and perform better on spatial memory tasks than their
      southern conspecifics. As elevated levels of corticosterone have been shown
      previously to correlate with spatial memory performance in chickadees, this study
      aimed to investigate whether black-capped chickadees from northern latitudes have
      elevated baseline levels of corticosterone and/or a stronger adrenocortical
      stress response than their southern conspecifics, irrespective of their immediate
      environment. We found no differences between Alaskan and Colorado chickadees
      maintained under identical conditions for 3 months in either baseline levels of
      corticosterone or maximum levels of corticosterone achieved during the stress
      response. Baseline corticosterone levels were negatively correlated with relative
      body mass across both groups of birds. Our results suggest that the population
      differences in food catching behavior and spatial memory were not related to
      differences in corticosterone levels. We conclude that many reported population
      differences in baseline levels and in strength of adrenocortical stress response
      may often reflect differences in local environmental conditions rather than
      population-specific physiological traits.

PMID- 14720596
TI  - Plasma corticosterone concentrations in males of the skink Egernia whitii during
      acute and chronic confinement, and over a diel period.
AB  - This study examined adrenal and gonadal responses to capture and to longer term
      captivity in males of the scincid lizard, Egernia whitii. Animals subjected to
      acute capture stress in the field exhibited a rapid rise in plasma corticosterone
      concentrations that had not attenuated by 4 h after capture; plasma testosterone
      concentrations decreased significantly over this period. Animals returned to
      captive conditions in the laboratory showed little change in plasma
      corticosterone concentrations by 1 week, but concentrations were significantly
      lower at 4 weeks. Plasma testosterone did not vary significantly during this
      period. Sampling over a diel period indicated that plasma corticosterone
      concentrations vary little over the daylight hours; however, there was a
      significant decrease between the samples taken at 17:00 h and 21:00 h. These
      results suggest that, as in other species, the acute adrenal response to capture
      stress may confound assessment of other physiological parameters, although if
      experiments are carried out during daylight hours, time of sampling should have
      little influence on plasma corticosterone concentrations. The results also
      suggest that males of E. whitii require at least a week to adapt to captivity,
      although further studies investigating different captive conditions are warranted
      for this social species.

PMID- 14720597
TI  - The Xenopus laevis cortical granule lectin: cDNA cloning, developmental
      expression, and identification of the eglectin family of lectins.
AB  - A Xenopus laevis egg cortical granule, calcium-dependent, galactosyl-specific
      lectin participates in forming the fertilization layer of the egg envelope and
      functions in establishing a block to polyspermy. We report the cDNA cloning of
      the lectin, expression of the cortical granule lectin gene during oogenesis and
      early development, and identification of a new family of lectins. The translated
      cDNA for the cortical granule lectin had a signal peptide, a structural sequence
      of 298 amino acids, a molecular weight of 32.7 K, contained consensus sequence
      sites for N-glycosylation and a fibrinogen domain. The lectin cDNA was expressed
      during early stages of oogenesis. Lectin glycoprotein levels were constant during
      development with 2/3 of the lectin associated with the extracellular
      perivitelline space and the egg/embryo fertilization envelope. Lectin mRNA levels
      were from 100- to 1000-fold greater in ovary than in other adult tissues. The
      lectin had no sequence homology to the previously identified lectin families. The
      lectin had 41-88% amino acid identity with nine translated cDNA sequences from an
      ascidian, lamprey, frog, mouse, and human. Based on the conserved carbohydrate
      binding and structural properties of these glycoproteins, we propose a new family
      of lectins, the eglectin family.

PMID- 14720598
TI  - Betaine improves growth, but does not induce whole body or hepatic palmitate
      oxidation in swine (Sus scrofa domestica).
AB  - Dietary betaine may reduce carcass fat in growing pigs. We explored the effects
      of betaine on short-term growth and in vivo and in vitro fatty acid oxidation.
      Pigs were housed in metabolism crates and fed diets containing either 0%
      (control), 0.125% or 0.5% betaine at 80% of ad libitum energy intake. Fatty acid
      oxidation was measured during intravenous infusions of 1-(13)C-palmitate and in
      hepatocytes incubated in the presence or absence of betaine and carnitine. CO2
      and palmitate isotopic enrichments were determined by mass spectrometry. Pigs
      consuming 0.125% and 0.5% betaine for at least 9 days had growth rates that were
      38% and 12% greater than controls, respectively. Feed efficiency was also
      improved with betaine. Fasting increased palmitate oxidation rates 7-8-fold (P <
      0.01), but betaine had no effect in either the fed or fasted state (P > 0.1). For
      hepatocytes, carnitine but not betaine enhanced palmitate oxidation. This
      response suggests that previously observed reduction in adipose accretion must be
      via a mechanism other than oxidation. Betaine had no effect on plasma non
      esterified fatty acids or urea nitrogen. Under the confinement conditions in this
      study, dietary betaine improved animal growth responses, but it had no apparent
      effect on either whole body or hepatic fatty acid oxidation.

PMID- 14720599
TI  - Standard and digestive metabolism in the banded water snake, Nerodia fasciata
      fasciata.
AB  - Estimating energy costs by respirometry is fundamental to many studies of the
      ecology, behavior and evolution of reptiles. However, traditional respirometry
      procedures seldom incorporate objective techniques for removal of outliers from
      estimates of metabolic parameters. We demonstrate how computer-automated
      respirometry equipment, which records many respiratory measurements over short
      intervals, can be coupled with mathematical procedures to produce robust
      estimates of pre- and post-prandial metabolism in banded water snakes (Nerodia
      fasciata fasciata). Standard metabolic rate of N. f. fasciata was estimated to be
      1.21 ml O2/h (mass = 30.21 +/- 0.74 g) at 25 degrees C. After ingestion of a fish
      equaling 20% of their body mass, snakes exhibited a fivefold increase in
      metabolic rate with peak O2 consumption rate (VO2) reaching 6.5 ml O2/h. Total
      cost of digestion was 5.44 kJ, equivalent to approximately 21% of the energy in
      the meal. Repeated measurements of metabolism in the same individuals revealed
      that our methods yielded similar results, even when individuals exhibited
      different patterns of VO2 variation between respiratory trials. Our results
      underscore the importance of obtaining many VO2 measurements, coupled with
      objective removal of outlier values from estimates of metabolic rate, especially
      when metabolic values are to be interpreted in a comparative context.

PMID- 14720600
TI  - Red muscle recruitment during steady swimming correlates with rostral-caudal
      patterns of power production in trout.
AB  - Rainbow trout (Oncorhynchus mykiss) and brook trout (or charr, Salvelinus
      fontinalis) display different rostral-caudal patterns of power production by the
      red or aerobic muscle during steady swimming. The anterior muscle of rainbow
      trout produces much less power for swimming than the posterior, while in brook
      trout there is no variation in power output. To determine if red muscle
      recruitment is associated with anterior-posterior patterns of power production,
      electromyography (EMG) was used to record red muscle activity at three body
      positions across a range of swimming speeds in fish of each species. The initial
      recruitment of the anterior red muscle in swimming rainbow trout was predicted to
      lag behind, i.e. occur at higher speeds, that of the posterior due to the
      variation in power production, but no variation in recruitment was expected for
      brook trout. Burst of red muscle EMG activity occurring with each tailbeat was
      analyzed for frequency (tailbeat frequency), duty cycle (DC) (duration of burst
      relative to the period of the tailbeat) and burst intensity (BI) (magnitude of
      the measured EMG activity). Brook trout swam with higher tailbeat frequencies and
      longer values of DC than rainbow trout. Both species showed a pattern of
      longitudinal variation in DC, with longer DC values in the anterior red muscle.
      BI also differed significantly along the length of rainbow trout but not brook
      trout. In the former, BI of anterior muscle was significantly less than the
      posterior at lower steady swimming speeds. The EMG data suggest that power
      production and muscle recruitment are related. In rainbow trout, where there is
      longitudinal variation in muscle power output, there are also significant rostral
      caudal differences in red muscle recruitment.

PMID- 14720601
TI  - Beta-Alanine and other free amino acids during salinity adaptation of the
      polychaete Nereis japonica.
AB  - The free amino acid pool was measured in the body wall muscle and in coelomic
      cells (eleocytes) of the polychaete Nereis japonica following adaptation to
      salinities between 6 and 44 per thousand. Beta-Alanine and glycine were the major
      amino acids comprising 35-60% of the total free amino acid pool in the body wall.
      In eleocytes, glutamate and lysine in addition to beta-alanine and glycine were
      the dominant free amino acids. In the body wall, the concentrations of beta
      alanine were closely correlated with the ambient salinity between 12 and 35 per
      thousand. The concentrations of glycine rose initially but remained unchanged at
      concentrations above 26 per thousand. In both body wall and eleocytes, the mean
      total primary amine concentrations were correlated with the ambient salinities
      between 12 and 35 per thousand. The sum of amino acids determined by HPLC showed
      the same correlation in both tissues, but accounted only for 60-85% of the
      concentrations of total primary amines. The total protein content of the body
      wall was slightly higher at 44 per thousand compared to the lower salinities
      indicating dehydration of the tissues. Eleocytes swell at 6 per thousand and
      showed irregular amino acid concentrations indicating a loss of metabolic
      integrity.

PMID- 14720602
TI  - Changes in intracellular calcium concentration in response to hypertonicity in
      bovine articular chondrocytes.
AB  - Intracellular calcium concentration ([Ca2+]i) in articular chondrocytes changes
      during mechanical challenges associated with joint movements, because of the
      fluctuation of the extracellular osmotic environment during joint loading. Matrix
      synthesis by chondrocytes is modulated by loading patterns, possibly mediated by
      variations in intracellular composition, including [Ca2+]i. The present study has
      employed the Ca(2+)-sensitive fluoroprobe Fura-2 to determine the effects of
      hypertonic shock on intracellular Ca2+ concentration ([Ca2+]i) and to
      characterise the mechanisms involved in the response for isolated bovine
      articular chondrocytes. In cells subjected to a hypertonic shock, [Ca2+]i rapidly
      increased by approximately 300%, reaching a maximal value within 50 s following
      the hypertonic shock with a recovery of more than 90% towards the initial [Ca2+]i
      within 5 min. The effect was inhibited by removal of extracellular Ca2+ ions, but
      not by thapsigargin, indicating that the rise in [Ca2+]i is only a result of
      influx from the extracellular medium. The rise was insensitive to inhibitors of L
      type voltage-activated Ca2+ channels, TRPV channels or stretch-activated cation
      channels. Non-specific inhibitors of Ca2+ channels like CdCl2, NiCl2, LaCl3 and
      ZnCl2 significantly attenuated the response, although the extent in which CdCl2
      and NiCl2 (both of them inhibitors of annexin-mediated Ca2+ fluxes) inhibited the
      response was significantly greater. The rise was also sensitive to KBR7943,
      inhibitor of NCE reverse mode and trifluoperazine, inhibitor of the activity of
      annexins. Hypertonic shock also produced also hyperpolarisation of chondrocytes
      (Em measured by means of Di-BA-C4(3), a membrane potential sensitive dye), which
      was inhibited by TEA-Cl and BaCl, but was not affected by changing the
      extracellular solution to Ca(2+)-free HBS. Inhibition of hyperpolarisation
      completely abolished the [Ca2+]i rise following hypertonic shock. Treatment with
      retinoic acid, which can increase the activity of annexins as Ca2+ transport
      pathways caused a significant increase in [Ca2+]i. The recovery of [Ca2+] was
      inhibited by benzamil and was dependent on extracellular Na+, but was unaffected
      by Na-orthovanadate, an inhibitor of plasma Ca(2+)-ATPase. We conclude that in
      response to hypertonic shock, NCE reverse mode and annexins are the pathways
      responsible for the [Ca2+]i increase, while forward mode operation of NCE is
      responsible for the subsequent extrusion of Ca2+ and recovery of [Ca2+]i towards
      initial values.

PMID- 14720604
TI  - Uptake of cadmium through isolated perfused gills of the Chinese mitten crab,
      Eriocheir sinensis.
AB  - Using the perfusion method, we compared cadmium accumulation and influx across
      the gills of the euryhaline Chinese mitten crab Eriocheir sinensis, exposed to
      4.8 microM cadmium in the incubation medium (OUT). Cadmium influx was not
      observed across posterior gills while it ranged from 0.15 to 6.82 nmol Cd g(-1)
      gill w.w. h(-1) across anterior ones. For these respiratory gills, a strong
      increase (40 times) was observed when calcium was removed in both incubation and
      perfusion media while the lack of sodium in the perfusion medium resulted in a 46
      times decrease. For crabs acclimated 15 days to artificial seawater, cadmium
      influx across anterior gills showed a 21 times decrease when compared with
      freshwater acclimated ones. On the other hand, after 3 h of perfusion, we
      detected cadmium accumulation in both types of gills, ranging from 3.8 to 68 nmol
      Cd g(-1) gill w.w. in anterior gills and from 2.1 to 39 nmol Cd g(-1) gill w.w.
      in posterior ones. Such accumulations represent between 61.3 and 100% of the
      total uptake of cadmium through the gills. From these results, we suggest that
      cadmium can penetrate more easily into the hemolymph space through the
      'respiratory' type epithelium present in the anterior gills but absent in the
      posterior ones. This metal uptake is likely to occur at least in part through the
      same pathways as calcium. On the contrary, cadmium seems to be sequestered inside
      the posterior gills, perhaps in the cuticle of the salt-transporting type
      epithelium.

PMID- 14720603
TI  - The hypothalamus is involved in the anorexic effect of glucagon-like peptide-1 in
      chicks.
AB  - The present study was carried out to investigate whether the hypothalamus is
      involved in the anorexic effect of glucagon-like peptide-1 (GLP-1) in chicks. To
      examine this, Fos expression in the chick hypothalamus were immunohistochemically
      detected after intracerebroventricular (ICV) injection of 30-pmol GLP-1. ICV
      injection of GLP-1 stimulated the expression of Fos-like immunoreactive (FLI)
      cells in the ventromedial hypothalamic nucleus (VMN). When 15-pmol GLP-1 was
      directly injected into the chick VMN, the chick's food intake was significantly
      decreased compared with the control treatment. Microinjection of GLP-1 into the
      (LHA) also inhibited feeding in chicks, although ICV injection of GLP-1 did not
      stimulate FLI expression in the brain area. These results suggest that VMN and
      some brain regions are involved in the anorexic effect of GLP-1 in chicks.

PMID- 14720605
TI  - Interplay between plasma hormone profiles, sex and body condition in immature
      hawksbill turtles (Eretmochelys imbricata) subjected to a capture stress
      protocol.
AB  - We investigated plasma hormone profiles of corticosterone and testosterone in
      immature hawksbill turtles (Eretmochelys imbricata) in response to a capture
      stress protocol. Further, we examined whether sex and body condition were
      covariates associated with variation in the adrenocortical response of immature
      turtles. Hawksbill turtles responded to the capture stress protocol by
      significantly increasing plasma levels of corticosterone over a 5 h period. There
      was no significant sex difference in the corticosterone stress response of
      immature turtles. Plasma testosterone profiles, while significantly different
      between the sexes, did not exhibit a significant change during the 5 h capture
      stress protocol. An index of body condition was not significantly associated with
      a turtle's capacity to produce plasma corticosterone both prior to and during
      exposure to the capture stress protocol. In summary, while immature hawksbill
      turtles exhibited an adrenocortical response to a capture stress protocol,
      neither their sex nor body condition was responsible for variation in endocrine
      responses. This lack of interaction between the adrenocortical response and these
      internal factors suggests that the inactive reproductive- and the current
      energetic- status of these immature turtles are important factors that could
      influence plasma hormone profiles during stress.

PMID- 14720606
TI  - Variation in gene expression in response to stress in two populations of Fundulus
      heteroclitus.
AB  - We used differential display PCR to identify hepatic genes responsive to handling
      stress and genes that differ in expression between populations of a fish,
      Fundulus heteroclitus, from different thermal environments. Despite substantial
      inter-individual variation, we cloned 20 putatively stress-regulated bands from
      Northern fish, 10 of which had high similarity to genes of known function. We
      selected five of these genes for further analysis based on their known roles in
      the stress response. Three of these genes (glucokinase, serine-threonine kinase
      10 and cRAF) were confirmed as stress-responsive using real-time PCR. These genes
      increased in expression in response to a 7-day chronic stress protocol in fish
      from the Southern population of F. heteroclitus, but did not change significantly
      in fish from the Northern population. These three genes also differed in
      expression between populations in control fish, suggesting a link between the
      response to chronic stress and inter-population differences in gene expression in
      unstressed laboratory-acclimated fish. Two genes that did not respond to stress
      (glycogen synthase kinase and warm acclimation-related protein (WAP)) also
      differed between populations. Expression of WAP was eight-fold higher in Southern
      than in Northern fish, consistent with a previously suggested role for this gene
      in thermal acclimation or adaptation in fish.

PMID- 14720607
TI  - Preen gland function in layer fowls: factors affecting morphology and feather
      lipid levels.
AB  - The effects of age and external factors on preen gland morphology and feather
      lipid concentrations in layer fowl (Gallus domesticus) have not previously been
      described. This work examines how floor substrate, whether a bird is feather
      pecked or not, and age influence both gross and histological morphology.
      Furthermore, the effects of age, beak trimming and floor substrate on feather
      lipid concentration (mg lipid per g feathers) are investigated. Neither absolute
      nor relative preen gland weight were reliably affected by floor substrate or
      feather pecked status. However, these parameters were strongly affected by
      changes in bird age and related body weight changes. The microstructures of the
      gland also increased consistently with age. Feather lipid concentration generally
      increased with age. Feather lipid was strongly influenced by the presence or
      absence of a dustbathing substrate. Of all the parameters tested here, the age
      and growth of the bird had the greatest effects on preen gland development.
      Feather lipid concentration is also influenced by age, and by the presence or
      absence of a dustbathing substrate.

PMID- 14720608
TI  - The ice worm, Mesenchytraeus solifugus, elevates adenylate levels at low
      physiological temperature.
AB  - The ice worm, Mesenchytraeus solifugus, is among a few metazoan species that
      survive exclusively in glacier ice/snow. In this study, we demonstrate that ice
      worm adenylate levels [i.e. adenosine 5'-triphosphate (ATP), ADP and AMP] are
      maintained at levels well above their mesophilic counterparts, and that their
      response to temperature change is distinctly opposite, namely, ice worms increase
      energy levels as temperatures fall. Initially, this response is characterized by
      a sharp spike in [ATP] and the adenylate energy charge (even at sub-zero
      temperatures), which is followed by corresponding increases in [ADP] and [AMP]
      within a few days. These results suggest that ice worms have evolved a
      compensatory mechanism by which gains in adenylate nucleotides off-set, at least
      in part, the inherent lethargy and death usually associated with cold
      temperature.

PMID- 14720609
TI  - Depolarisation and repolarisation sequences of ventricular epicardium in chickens
      (Gallus gallus domesticus).
AB  - Activation and recovery sequences were mapped by means of 64-channel synchronous
      recording of extracellular potentials on ventricular epicardium in chickens.
      Ventricular epicardium was depolarized due to multiple breakthroughs. The
      recovery of ventricular epicardium occurs from the apex to the base of heart and
      does not repeat the activation sequence. Gradients of repolarisation exist over
      the ventricular epicardium in birds. Repolarisation pattern of ventricular
      epicardium depends primarily on intrinsic spatial heterogeneities of ARIs over
      epicardium.

PMID- 14720611
TI  - A new year's resolution for reproductive health care.

PMID- 14720612
TI  - Serum medroxyprogesterone acetate levels in new and repeat users of depot
      medroxyprogesterone acetate at the end of the dosing interval.
AB  - In the absence of published data on serum medroxyprogesterone acetate (MPA)
      levels in South African users, this study examines such levels in new and repeat
      users of depot medroxyprogesterone acetate at the end of the dosing interval. The
      study was undertaken at three family-planning clinics in Durban, South Africa.
      Serum MPA levels were measured in 94 Black African, Indian and White women
      returning between 11 and 14 weeks after their last injection. The median serum
      MPA level was 0.88 (range, <0.04-1.77) ng/mL and wide interindividual variability
      was observed. Levels in all but one woman were higher than 0.1 ng/mL, the level
      at which ovulation is reported to resume. MPA levels were not found to vary
      according to weight, body mass index or ethnicity. Although there was a slight
      tendency towards higher MPA levels with longer duration of use (r = 0.13), the
      wide interindividual variability precluded the possibility of determining whether
      this was a real trend. A prospective study, using standardized assay techniques
      and following individual women, is required to further clarify this issue.

PMID- 14720613
TI  - A comparison of the fertile phase as determined by the Clearplan Easy Fertility
      Monitor and self-assessment of cervical mucus.
AB  - The purpose of this study was to compare the fertile phase of the menstrual cycle
      as determined by the Clearplan Easy Fertility Monitor (CPEFM) with self
      monitoring of cervical mucus. One-hundred women (mean age = 29.4 years) observed
      their cervical mucus and monitored their urine for estrogen and luteinizing
      hormone metabolites with the CPEFM on a daily basis for 2-6 cycles and generated
      378 cycles of data; of these, 347 (92%) had a CPEFM peak. The beginning of the
      fertile window was, on average, day 11.8 (SD = 3.4) by the monitor and day 9.9
      (SD = 3.0) by cervical mucus (r = 0.43, p < 0.001). The average first day of peak
      fertility by the monitor was 16.5 (SD = 3.6) and by cervical mucus 16.3 (SD =
      3.7) (r = 0.85, p < 0.001). The mean length of the fertile phase by the monitor
      was 7.7 days (SD = 3.1) and by cervical mucus 10.9 days (SD = 3.7) (t = 12.7, p <
      0.001). The peak in fertility as determined by the monitor and by self-assessment
      of cervical mucus is similar but the monitor tends to underestimate and self
      assessment of cervical mucus tends to overestimate the actual fertile phase.

PMID- 14720614
TI  - Periodic abstinence in developing countries: an assessment of failure rates and
      consequences.
AB  - It is estimated that 27 million couples, representing 2.6% of all couples in the
      reproductive span, use periodic abstinence (PA). Using data from 15 national
      surveys in low and middle-income countries, this article assesses characteristics
      of PA users, knowledge of the fertile period, accidental conceptions while using
      PA and the reproductive consequences of these conceptions. Current users of PA
      (predominantly the simple calendar variant) tend to be more educated and urban
      than users of other methods. The method is preferred by young single women and
      older married women. The proportion of users with correct knowledge of the timing
      of ovulation ranges from 8% to 91%, with a median value of 62%. The median 12
      month gross failure rate was 24 per 100 episodes. Net of other predictors of
      failure, correct knowledge of the timing of ovulation was associated with a 12%
      decrease in failure probabilities. Couples who experienced PA failure were more
      likely than couples who experienced failure with another method to carry the
      pregnancy to term. Nevertheless, PA still contributes to one-sixth of all
      abortions (or miscarriages) following contraceptive failure.

PMID- 14720615
TI  - An open-label randomized comparative study of oral contraceptives between
      medications containing 3 mg drospirenone/30 microg ethinylestradiol and 150
      microg levonogestrel/30 microg ethinylestradiol in Thai women.
AB  - This study was conducted to compare the cycle control, efficacy and adverse
      events of a new low-dose oral contraceptive pill regimen containing 3 mg
      drospirenone (DRSP)/30 microg ethinylestradiol (EE), with a widely prescribed 150
      microg levonogestrel (LNG)/30 microg EE. The results of this comparative trial
      demonstrated that the two preparations had no statistically significant
      difference in terms of cycle control, efficacy and adverse events. The occurrence
      of spotting and breakthrough bleeding was low and was not different between the
      two regimens. There was neither amenorrhea nor pregnancies reported in either
      group. The most common adverse events in both groups were nausea, headache and
      breast tenderness. Also statistically significant changes were found in body
      weight and blood pressure in both groups at the end of the study. In conclusion,
      the 3 mg DRSP/30 microg EE regimen provides good cycle control with reliable
      contraceptive efficacy and a low incidence of adverse events equal to the 150
      microg LNG/30 microg EE preparation. Compared with the 150 microg LNG/30 microg
      EE preparation, the 3 mg DRSP/30 microg EE preparation demonstrated a more
      favorable effect on body weight and blood pressure, with the mean body weight and
      mean blood pressure remaining lower than baseline mean. The new formulation may
      be especially beneficial for women susceptible to body weight gain and rise in
      blood pressure.

PMID- 14720616
TI  - Increased titer of anti-beta2-glycoprotein I IgG antibody among factor V Leiden
      carriers during oral contraceptive use.
AB  - The risk of thromboembolism during oral contraceptive (OC) use is increased among
      factor V Leiden (FVL) carriers compared to women with wild-type genotype of the
      gene for coagulation factor V (FV). The carrier frequency in the general
      population is too high for FVL alone to be responsible for the reported
      association. Additional risk factors may be required to explain the increased
      risk of thromboembolism of carriers during OC use. We conducted a case-control
      study to compare the titer of anti-beta2-glycoprotein I immunoglobulin G (IgG)
      and the frequency of elevated titer of IgG type anti-beta2-glycoprotein I
      antibody between FVL carriers and individuals with FV wild-type genotype with and
      without pill use. An asymptomatic population of 313 unrelated nonpregnant women
      were screened for FVL and for the presence of anti-beta2-glycoprotein I IgG
      antibody. Sixty-six women were FVL carriers and 247 had normal genotype. One
      hundred and thirty-five women used OC at the time of screening and 178 did not.
      Among FVL carriers, OC pill users had a higher mean anti-beta2-glycoprotein I IgG
      titer than nonusers (9.2 SGU/mL vs. 4.7 SGU/mL, p = 0.0485). Among women with FV
      wild-type genotype, there was no significant difference in anti-beta2
      glycoprotein I IgG titers between users and nonusers of OCs (6.4 SGU/mL and 6.0
      SGU/mL, respectively; p = 0.7010). The odds of an elevated anti-beta2
      glycoprotein I IgG titer during OC use in FVL heterozygous women was 2.41 (95%
      confidence interval: 0.79-7.39) relative to users with-type genotype. FVL may
      contribute to the development of elevated titer of IgG type anti-beta2
      glycoprotein I antibody during OC use. The elevated titer of IgG type anti-beta2
      glycoprotein I antibody may select women among FVL carriers during OC use with an
      increased risk of thromboembolism.

PMID- 14720617
TI  - What women believe about oral contraceptives and the effect of counseling.
AB  - OBJECTIVES: To evaluate Canadian women' s knowledge of the risks, benefits and
      side effects of oral contraceptives (OCs) and the effect of counseling. STUDY
      DESIGN: Six-hundred and forty-nine Canadian women filling an OC prescription at
      Shopper's Drug Mart stores completed the survey. Respondents recorded whether or
      not they had discussed 12 separate issues about OC use with their healthcare
      provider. Optimal responses to multiple-choice questions were compared between
      those reporting counseling to those reporting no counseling, using Fisher's Exact
      Tests. Women were also questioned on what they were told about associated cancer
      risks. RESULTS: Eighty percent or more of the women selected the optimal response
      for the questions relating to dysmenorrhea, leg pain and co-medication. Less than
      half of survey respondents identified the optimal response for nausea,
      breakthrough bleeding, breast tenderness, acne, headaches and weight change.
      Counseling made a significant impact on selection of the optimal response for 7
      of the 12 questions (p < 0.004, adjusted significance level). Fifty-two percent
      indicated that they did not know what they were told about the risk of uterine
      and ovarian cancer when on the pill. A significant proportion of women said they
      would phone their physician for relatively minor problems such as breakthrough
      bleeding (65%), breast tenderness (55%) and acne (54%). CONCLUSIONS: The
      knowledge level of Canadian women on the pill regarding risks, benefits and side
      effects of the pill remains deficient in several key areas. Adequate counseling
      by healthcare providers can help women recognize the pill's positive health
      benefits, and may result in fewer unnecessary physician contacts and unwanted
      pregnancies.

PMID- 14720618
TI  - Attitude of German women and gynecologists towards long-cycle treatment with oral
      contraceptives.
AB  - Long-cycle regimens with continuous use of oral contraceptives (OCs) for 3 or 6
      months followed by a hormone-free interval of 7 days may reduce or prevent cycle
      dependent and menses-related complaints. A representative survey carried out with
      1195 German women in different age groups revealed that only 26-35% of the women
      aged between 15 and 49 years preferred monthly bleeding, while 37-46% wished to
      never bleed. The reasons for the refusal of regular menstruations were fewer
      severe menstrual complaints, better hygiene, higher quality of life, and less
      blood loss. Among the women who preferred regular withdrawal bleeding during the
      use of OCs, the main reasons were fear of pregnancy, infertility and adverse
      effects, and that menstruations were natural. Between 32% and 54% of the women
      would suppress menstruation sporadically and 11-14% for a longer period of time.
      After continuous treatment with a combination of 30 microg ethinyl estradiol and
      2 mg dienogest for 6 months, the majority of women preferred the long-cycle
      regimen as compared to the conventional OC regimen despite a higher rate of
      irregular bleeding. Bleeding occurred primarily in first-time users of OC,
      particularly during the administration of the second OC pack. A survey carried
      out with German gynecologists revealed that most physicians prescribed extended
      OC cycles primarily for medical reasons, e.g., dysmenorrhea, hypermenorrhea,
      endometriosis and premenstrual dysphoric disorder. The gynecologists preferred a
      regimen with three packs of extended use of OCs.

PMID- 14720619
TI  - Emergency contraception: prescribing practices of general internists compared
      with other primary care physicians.
AB  - Primary care physicians of all specialties should be familiar with prescribing
      emergency contraception (EC). We conducted a mail survey of 282 randomly sampled
      physicians in general internal medicine (31%), family medicine (34%) and
      obstetrics-gynecology (35%). Experience with prescribing EC significantly
      differed by specialty (63% of general internists, 76% of family physicians, and
      94% of obstetrician-gynecologists, p < 0.0001). Controlling for year of
      graduation, gender, religion and practice location, family physicians [adjusted
      odds ratio (OR): 2.5, 95% confidence interval (CI): 1.2-5.2] and obstetrician
      gynecologists (adjusted OR: 11.2, 95% CI: 4.0-31.3) were still significantly more
      likely to have ever prescribed EC than general internists. Efforts to increase
      awareness and knowledge of EC should be aimed at general internists since they
      provide primary care for many reproductive age women.

PMID- 14720620
TI  - Use of erythromycin for nonsurgical female sterilization in West Bengal, India: a
      study of 790 cases.
AB  - OBJECTIVE: Determine if erythromycin is an effective agent for achieving
      occlusion of the Fallopian tube for nonsurgical female sterilization. METHODS:
      Two studies of 100 healthy volunteers requesting sterilization were planned, one
      in Julpia Andhermanik and the other in Kolkata (Calcutta). A readily available
      marketed tablet preparation containing 500 mg of the estolate salt of
      erythromycin was used for the trial. In one study (Bishnupur), the tablet was
      crushed before placing in a copper-T IUD inserter for placement at the fundus. In
      the other study (Kolkata), crushed tablets were processed into 50 mg pellets of
      the same diameter as standard quinacrine pellets and 10 pellets were inserted at
      the fundus using aseptic precautions. Procedures in each study were repeated at
      30 days. Oral contraceptives were prescribed for three cycles following first
      insertion. No incentive was offered for participation in the trial. Follow-up
      treatment, including first-trimester abortion for pregnancy due to failure of the
      sterilization procedure, was assured without charge. Due to extraordinary patient
      demand, one study (Bishnupur) was expanded to 690 cases for reasons of
      compassion. RESULTS: At 12 months of use, the failure rate of the sterilization
      procedure for the crushed 500 mg tablets was 35.8% (SE = 1.8) with 417 women at
      risk. At 12 months of use, the failure rate for the erythromycin pellets was
      28.6% (SE = 5.0) with 43 women at risk. There were no serious complications
      reported in either trial. All pregnancies resulting from failure of the
      sterilization procedure were terminated by menstrual regulation within 10 weeks
      gestation. CONCLUSIONS: The failure rate in this study is unacceptably high for
      erythromycin to be used as a sterilization method.

PMID- 14720621
TI  - Midtrimester medical termination of pregnancy: a review of 1002 consecutive
      cases.
AB  - We assessed the effectiveness, safety and factors that affected the outcome of
      midtrimester medical termination of pregnancy at 13-21 weeks gestation. Of the
      1002 women, 3 took mifepristone and decided to continue with the pregnancy, with
      999 women being compliant with the regimen. Of these, 2 women aborted prior to
      administration of misoprostol and 970 (97.1%) aborted successfully within five
      doses of misoprostol. Surgical intervention was necessary to complete the
      abortion process in 81 (8.1%) women. Women with no previous pregnancy (p = 0.02),
      no previous live birth (p = 0.0001) and gestations 17-21 weeks (p = 0.001)
      required more prostaglandin. Younger women (p = 0.0001) and women with a previous
      live birth (p = 0.001) were more likely to have a successful abortion. The
      induction abortion interval was significantly longer with increasing gestation
      [95% confidence interval (CI) difference in means: -2.52 to -0.89, p = 0.0001],
      increasing age (p = 0.0001) and no previous live birth (95% CI difference in
      means: -0.25 to -1.01, p = 0.0001). Surgical intervention was more likely to be
      required with increasing age (p = 0.008). Mifepristone in combination with
      misoprostol is a safe and effective regimen for midtrimester medical abortion
      with younger women and those with a previous live birth more likely to have a
      successful abortion.

PMID- 14720622
TI  - Effect of nurses' attitudes on hospital-based abortion procedures in
      Massachusetts.
AB  - Our study explored a largely unacknowledged obstacle to abortion access in
      Massachusetts: the unwillingness of nurses to staff abortion procedures. Evidence
      suggests that nurses tend to be more likely to oppose abortion than other medical
      professionals. However, the attitudes and practices of hospital-based nurses
      regarding abortion have not been thoroughly investigated. We collected
      qualitative information from physicians and nurse managers to understand how
      nurses' attitudes affect hospital-based abortion services in Massachusetts. We
      surveyed key respondents at all hospitals in Massachusetts where abortion
      services are available to any woman who requests them. Of the 20 individuals who
      responded (87%), 17 were physicians and 3 were nurse managers. We found that over
      half of physician respondents believed that the unavailability or unwillingness
      of nurses to staff abortions is a slight or moderate problem, and nearly a
      quarter of physician respondents characterized it as a large or very large
      problem. Thus, nurses' attitudes towards abortion and their unwillingness to
      assist with procedures may hinder patient access to abortion services.

PMID- 14720623
TI  - The medical abortion experiences of married and unmarried women in Tunis,
      Tunisia.
AB  - CONTEXT: The study explores the social dimensions of abortion in Tunisia and
      offers evidence supporting the provision of medical abortion to special
      populations, such as young and unmarried women. METHODS: For this study we
      recruited 222 women (unmarried: n = 101, married: n = 121) at three clinics in
      Tunis, Tunisia, from April 1999 to March 2001. All eligible women who consented
      to participate were administered a simplified regimen of medical abortion
      consisting of 200 mg oral mifepristone + 400 microg oral misoprostol 2 days later
      either at home or in the clinic. RESULTS: Our results demonstrate that unmarried
      women (94.8%) are as likely as married women (94.1%) to have a successful
      abortion using this regimen. We noted a strong initial preference for home
      administration of misoprostol among both groups (unmarried: 73.3%, married:
      80.2%), which grew even stronger after the procedure. Women indicated that home
      administration is desirable because transportation to the clinic is expensive
      (32.7%), home administration is more confidential (26.3%), easier and more
      convenient (12.8%). Both groups expressed a high degree of satisfaction with the
      method. CONCLUSIONS: Medical abortion with the option of home administration of
      misoprostol is safe and feasible for special populations; such as unmarried women
      in Tunisia.

PMID- 14720624
TI  - Comparison of nonselective cyclo-oxygenase (COX) inhibitor and selective COX-2
      inhibitors on preimplantation loss, postimplantation loss and duration of
      gestation: an experimental study.
AB  - Comparison of effect of three cyclo-oxygenase (COX) inhibitors, indomethacin,
      nimesulide and celecoxib, on the following were assessed: preimplantation loss,
      postimplantation loss and duration of gestation in Wistar rats. Indomethacin (2.5
      and 10 mg/kg), nimesulide (10 and 40 mg/kg) and celecoxib (10 and 40 mg/kg) were
      administered by gavage daily from days 1-7 for preimplantation loss studies and
      from day 13 to completion of gestation for postimplantation and duration of
      gestation studies. Number of animals in each group was six. Preimplantation loss
      was calculated by subtracting number of implantation sites from number of luteal
      spots and postimplantation loss was calculated by noting the difference between
      implantation sites and pups delivered. The higher doses of the three drugs were
      shown to increase significantly the preimplantation loss, while all the doses of
      three drugs produced a significant increase in postimplantation loss. Number of
      animals crossing upper limit of 23-day normal gestation period in Wistar rats was
      increased in the higher doses. At comparable dose levels, there was no
      significant difference among the three drugs.

PMID- 14720625
TI  - "Medical" and "surgical" abortion: rethinking the modifiers.

PMID- 14720626
TI  - Minimum effectiveness of the levonorgestrel regimen of emergency contraception.
AB  - The standard method for estimating the effectiveness of emergency contraceptive
      pills (ECPs) uses external data to calculate the proportion of expected
      pregnancies averted by the treatment. Because these data may not be applicable to
      ECP study populations, this approach could result in substantial overestimation
      of effectiveness. We used data from two published randomized trials of the
      levonorgestrel and Yuzpe ECP regimens to calculate the minimum effectiveness of
      the levonorgestrel regimen. Conservatively assuming that the Yuzpe regimen was
      entirely ineffective in these trials, we estimate that the levonorgestrel regimen
      prevented at least 49% of expected pregnancies (95% confidence interval: 17%,
      69%). Because physiologic data suggests that the Yuzpe regimen does, in fact,
      have some efficacy, the effectiveness of the levonorgestrel regimen is likely to
      be higher than our minimum estimate.

PMID- 14720627
TI  - Ectopic pregnancies following emergency levonorgestrel contraception.

PMID- 14720628
TI  - Ectopic pregnancies following emergency levonorgestrel contraception.

PMID- 14720630
TI  - Improving health security: a pilot study from Finland linking disability and
      health expenditures.

PMID- 14720631
TI  - Satisfaction with and access to community care of the chronically ill in Israel's
      health system.
AB  - One goal of Israel's National Health Insurance Law was to improve services for
      vulnerable populations. However, it was feared that this goal would not be
      reached for the chronically ill, due to the regulations governing health plan
      reimbursement and to amendments to the law that authorize additional co-payments
      for services. OBJECTIVE: To examine the satisfaction with and organizational and
      financial access to services of chronically ill patients, and compare them to
      those of healthy consumers. METHODS: In autumn 2001, telephone interviews were
      conducted with a random sample of 1790 permanent residents of Israel over age 22,
      512 (28%) of whom reported having a chronic illness. RESULTS: No significant
      differences were found between chronically ill and healthy respondents in
      satisfaction with services, and few differences were found in organizational
      access to services. However, differences were found in financial access to
      services. Specifically, chronic illness had an independent positive effect on the
      burden of co-payments for health services and the likelihood of forfeiting care
      or medication due to cost. CONCLUSIONS: Increased co-payments for services may
      restrict access to care. To lighten the burden on vulnerable populations, it is
      necessary to consider discounts and lower ceilings on co-payments.

PMID- 14720632
TI  - Accessibility and the Canadian health care system: squaring perceptions and
      realities.
AB  - The 1984 Canada Health Act (CHA) is the major piece of Federal legislation that
      governs health care accessibility in the provinces and territories. According to
      the CHA, all provinces and territories in Canada must uphold five principles in
      order to receive federal funding for health care (universality,
      comprehensiveness, portability, public administration, and accessibility). In
      Canada, there are competing views among policy makers and consumers about how the
      CHA's principle of accessibility should be defined, interpreted and used in
      delivering health care. During the 1990s, the health care perceptions of
      Canadians and their health care behaviours were measured through both public
      opinion polls and Statistics Canada's National Population Health Survey (NPHS).
      The goal of this paper is to examine perceptions of accessibility in public
      opinion polls and actual accessibility as measured through the NPHS. Public
      opinion polls demonstrate that while Canadians want to preserve the principles of
      the CHA, a majority of Canadians are losing confidence in their health care
      system. In contrast, the results from the NPHS reveal that only 6% of Canadians
      aged 25 years and older have experienced accessibility problems. Among those who
      report access problems, the barriers to accessibility are linked to specific
      socio-economic, socio-demographic and health characteristics of individuals. We
      discuss these findings in the context of the current debates surrounding
      accessibility within the CHA and the Canadian health care system.

PMID- 14720633
TI  - Incentives and pharmaceutical reimbursement reforms in Spain.
AB  - The aim of this paper is to assess whether cost containment has been affected by
      recent pharmaceutical reimbursement reforms that have been introduced in the
      Spanish health care system over the period 1996-2002, under the conservative
      Popular Party Government. Four main reimbursement policies can be observed in the
      Spanish pharmaceutical market after 1996, each of them largely unintegrated with
      the other three. First, a second supplementary negative list of excluded
      pharmaceutical products was introduced in 1998. Second, a reference pricing (RP)
      system was introduced in December 2000, with annual updating and enlargement.
      Third, the pharmacies' payment system has moved from the traditional set margin
      on the consumer price to a margin that varies according to the consumer price of
      the product, the generic status of the product, and the volume of sales by
      pharmacies. And fourth, general agreements between the government and the
      industry have been reached with cost containment objectives. In the final section
      of this paper, we present an overall assessment of the impact of these
      pharmaceutical reimbursement policies on the behaviour of the agents in the
      pharmaceutical market.

PMID- 14720634
TI  - South African Academic Health--the future challenge.
AB  - In South Africa, significant changes in Academic Health have taken place since
      the first democratic elections in 1994. Academic Health came from a separated
      academic hospital, departmental-based curriculum and research focussed on
      achievement, and an abundance of money, to a position of integrated service
      delivery with specific reference to primary health care, separation of service
      levels, a new integrated curriculum, research focussed according to the need and
      contract research, and financial constraints with limited budgets. The management
      of this change is a task challenging the manager in all fields of Academic
      Health. Leaders need to know their environment and organisation to be able to
      manage change. Academic Health centres are experiencing major changes as a result
      of the effects of managed care, reduced rate and growing expenditure on health
      services. In addition to restructuring of the clinical services, Academic Health
      centres are being challenged to sustain their academic mission and priorities in
      the face of resource constraints. In order to tackle these challenges,
      institutions need physicians in administrative positions at all levels who can
      provide leadership and thoughtful managerial initiatives. The future challenge
      for managers focuses on service delivery, research, health education and
      training, Academic Health management, professionalism and financial management.

PMID- 14720635
TI  - Fend for yourself. Systemic failure in the Dominican health system.
AB  - Despite relatively high levels of total spending and enormous growth in the
      supply of services during five decades, the Dominican health system demonstrates
      low performance in addressing the health needs of its population, ensuring
      acceptable quality of care, reducing the financial burden of health care on the
      poor, or providing adequate insurance coverage for those with the ability to pay.
      The paper analyzes deficiencies in financing, organization and delivery of health
      services in both the public and private sectors. The paper argues that government
      failure has undermined the health system and health care. Despite calls for
      reforms, attempts to restructure the system have not yet taken shape.

PMID- 14720636
TI  - Discounting in decision making: the consistency argument revisited empirically.
AB  - Discounting is one of the prominent topics of debate in health economics. While
      the standard practice in economic evaluation is to discount costs and effects
      alike with a 3-5% discount rate, many have raised questions about this practice.
      The debate sometimes seems trapped in Weinstein and Stason's consistency
      argument. In this paper, we use a set of health care programs--resembling
      Weinstein and Stason's hypothetical programs--to test whether appointed societal
      decision makers are consistent in their preferences over present and future costs
      and health effects, and whether they discount costs and effects at the same rate.
      Our results demonstrate these appointed decision makers to be fairly inconsistent
      on both issues, susceptible to the framing of problems and in part myopic. In
      other words, our respondents appear to be incapable of providing reasonable and
      consistent preferences between present and future costs, and health effects for
      use in economic evaluations. There is some support for the idea that rather than
      using constant and identical rates for costs and effects, real differences in
      health endowment over time (the growth rate for health) could serve as a basis
      for discount rates. Our respondents seem to relate their discount rate for health
      to their expectations about future life expectancy, but this also is dependent on
      the elicitation method.

PMID- 14720637
TI  - Impact of the case payment reimbursement method on the utilization and costs of
      laparoscopic cholecystectomy.
AB  - The purpose of this study was to examine the relationship between adoption of
      case payment for laparoscopic cholecystectomy (LC) and the growth rate of LC,
      outcomes of patients undergoing LC, and total healthcare expenditures on
      cholecystectomy. We used the claims data from Bureau of National Health Insurance
      (BNHI) to identify patients who underwent LC and open cholecystectomy (OC). Data
      were available from January 1996 to October 1997 and from January 1998 to October
      1999, enabling use to compare data from before and after the introduction of the
      new case payment system. Results showed that the volume and the proportion of LCs
      increased after adoption of the new payment method. We did not find a sharp
      increase in the cholecystectomy rate during the study period. In terms of
      outcomes, the admission rate for emergencies decreased; the surgery mortality
      rate decreased, but the readmission rate increased. The average cost and length
      of hospital stay for LC subjects decreased; however, the total cost of
      cholecystectomy increased. The impact on LC of the introduction of a case payment
      method failed to reduce total health expenditures for cholecystectomy.

PMID- 14720638
TI  - The organisation and development of primary care pharmacy in the United Kingdom.
AB  - Primary care pharmacists carry out clinical and administrative work directly for
      family doctors and primary care organisations. They are a relatively recent
      innovation and their role in the United Kingdom (UK)'s National Health Service
      (NHS) is still developing. The economic liberalization of the NHS in the 1990s
      seems to have provided a major stimulus for the growth of primary care pharmacy.
      The establishment of the new professional group was not linked to a deliberate
      plan or change in health policy with respect to pharmacist development. Primary
      care pharmacy practice is much more varied and flexible than traditional pharmacy
      practice in the community and hospitals. Standards and professional organisation
      for primary care pharmacy are slowly emerging. Modernization of the NHS is
      providing many new opportunities, which primary care pharmacists are well placed
      to take advantage of. Traditional community pharmacy faces many problems unless
      it can learn to develop alongside primacy care pharmacy. Pharmaceutical care is
      set to improve in the United Kingdom, but the precise nature of future services
      and providers remains uncertain.

PMID- 14720639
TI  - Using risk analysis in Health Impact Assessment: the impact of different relative
      risks for men and women in different socio-economic groups.
AB  - The aim of this study is to contribute to the emerging field of quantification of
      Health Impact Assessment (HIA), by analysing how different relative risks affect
      the burden of disease for various socio-economic groups (SES). Risk analysis,
      utilising attributable and impact fraction, raises several methodological
      considerations. The present study illustrates this by measuring the impact of
      changed distribution levels of smoking on lung cancer, ischemic heart disease
      (IHD), chronic obstructive lung disorder (COLD) and stroke for the highest and
      lowest socio-economic groups measured in disability adjusted life years (DALY).
      The material is based on relative risks obtained from various international
      studies, smoking prevalence (SP) data and the number of DALY based on data
      available for Sweden. The results show that if smoking would have been eliminated
      (attributable fraction, AF), the inequality between the highest and lowest socio
      economic groups may decrease by 75% or increase by 21% depending on the size of
      the relative risk. Assuming the same smoking prevalence for the lowest socio
      economic group as for the highest (impact fraction), then the inequality may
      decrease by 7-26%. Consequently, the size of the relative risk used may have a
      significant impact, leading to substantial biases and therefore should be taken
      into serious consideration in HIA.

PMID- 14720640
TI  - Is publicly funded health care really distributed according to need? The example
      of cardiac rehabilitation in the UK.
AB  - OBJECTIVES: To demonstrate the importance of measuring both the horizontal and
      vertical components of equity in order to examine whether patients are receiving
      the health care that they need. METHODS:  DESIGN: A theoretical demonstration
      followed by analysis of a prospectively collected national random sample of acute
      cardiac admissions to 94 hospitals in the UK. PATIENTS: 1064 patients under 70
      years old. ANALYSIS: The association between use of cardiac rehabilitation and
      gender (after adjusting for clinical need) was measured using multivariable
      analysis with effect modification. RESULTS: Hypertensive males were nearly twice
      as likely to undergo rehabilitation compared to hypertensive females (OR 1.76,
      95% CI 1.03-3.02). Hyertensive patients were less likely to undergo
      rehabilitation than normotensive patients (OR 0.67, 95% CI 0.50-0.89) but this
      treatment difference did not apply in the same way to both men and women.
      Hypertensive women were half as likely to undergo rehabilitation compared with
      normotensive women (OR 0.48, 95% CI 0.30-0.78), whereas hypertensive men were as
      likely as normotensive men to receive rehabilitation (OR 1.00. 95% CI 0.63-1.60).
      CONCLUSIONS: Horizontal inequity was demonstrated because male and female
      hypertensive patients with equal needs were not treated equally. There was also
      vertical inequity because although patients with hypertension were treated
      differently to normotensive patients, this treatment difference was not the same
      for men and women.

PMID- 14721768
TI  - Mechanisms involved in ultraviolet light-induced immunosuppression.
AB  - Ultraviolet radiation (UV) represents one of the most important environmental
      factors affecting human health, especially with regard to its hazardous effects
      on the generation of skin cancer, suppression of the immune system and premature
      skin aging. At molecular level, various chromophores have been identified, and
      DNA remains the major chromophore in the skin. Epidermal Langerhans cells (LC)
      are considered as the main targets of UV, as UV inhibits their antigen-presenting
      activity and their capacity to stimulate allogeneic type 1 T cells. Keratinocytes
      are also a target of UV light and they produce and release numerous soluble and
      immunosuppressive mediators. In human skin, IL-10 is mainly produced by dermis
      CD11b + macrophages and neutrophils that infiltrate epidermis after intense UV.
      UV-induced immunosuppression is transferable with suppressor T cells whose
      phenotype is still debated (Natural Killer T cells and T regulatory type 1
      cells). Although the mechanisms by which immune regulatory suppressor T cells act
      still remain unclear, there is increasing evidence that apoptosis of epidermal LC
      or reactive T cells may play an important role through the Fas/FasL system.

PMID- 14721769
TI  - Olmsted syndrome with squamous cell carcinoma of extremities and adenocarcinoma
      of the lung: failure to detect loricrin gene mutation.
AB  - Olmsted syndrome is an uncommon disorder of keratinization that presents
      mutilating palmoplantar keratoderma, periorificial hyperkeratosis, leukokeratosis
      and alopecia. We report a new case of this rare syndrome diagnosed in 48-year-old
      woman who developed several squamous cell carcinomas of limbs and adenocarcinoma
      of the lung. She has been followed up for about 40 years and osteolytic changes
      of the fingers and toes accompanied the keratinizing disorder and squamous cell
      carcinoma. Loricrin gene mutation that is occasionally observed in loricrin
      keratoderma such as Vohwinkel's syndrome was not detected in the present case.

PMID- 14721770
TI  - Cutis laxa of the autosomal recessive type in a consanguineous family.
AB  - Cutis laxa comprises a group of uncommon disorders of elastin fibers first
      described by Graf in the early 19th century. The main characteristic is a
      redundant, loose skin with deep wrinkling or sagging combined with a variable
      systemic involvement. Histopathologic examination presents various abnormalities
      of the elastin fibers. We distinguish congenital as well as acquired forms of
      generalized or localized cutis laxa. The mode of inheritance shows great
      heterogeneity: autosomal dominant, autosomal recessive and X-linked recessive
      inheritance have all been described. We present a severe case of autosomal
      recessive type 1 cutis laxa in a female patient, born in a large, consanguineous
      Turkish family, where three other family members had already died of the disease.
      A missense mutation of fibulin-5 was identified in this patient.

PMID- 14721771
TI  - Extensive speckled lentiginous nevus associated with giant congenital melanocytic
      nevus: an unusual example of twin spotting?
AB  - A 15-year-old boy had an unusual combination of giant congenital melanocytic
      nevus on his back and a large speckled lentiginous nevus arranged in a
      checkerboard pattern on the dorsal and lateral aspects of his trunk. The two
      pigmentary nevi showed distinguishing features both clinically and
      histopathologically. The speckled lentiginous nevus was not noted at birth but
      became visible during childhood. We hypothesize that this uncommon co-occurrence
      may represent a further example of twin spotting and may be categorized as a new,
      distinct type of phacomatosis.

PMID- 14721772
TI  - Unilateral facial telangiectases suggest type 1 segmental manifestation of Osler
      Rendu-Weber syndrome in an 11-year-old boy.
AB  - An 11-year-old boy revealed multiple telangiectases confined to the left cheek
      and the left side of the lips. Additionally, unilateral epistaxis was present.
      Radiological examinations of the brain, lungs and abdomen were normal and
      bleeding of the gastrointestinal tract was excluded. In this case, we propose a
      probable segmental type 1 manifestation of the autosomal dominantly inherited
      Osler-Weber-Rendu syndrome.

PMID- 14721773
TI  - Immunosuppressive antimetabolites inhibit induction of contact hypersensitivity
      while lymphoablative drugs also prevent its expression.
AB  - Contact hypersensitivity is one of the most common skin diseases and its
      pharmacological control is an important clinical issue. We investigated the
      control of contact hypersensitivity by immunosuppressive drugs administered
      during sensitization or challenge. Mycophenolate mofetil, methotrexate and 5
      fluorouracil completely inhibited contact hypersensitivity when administered
      during sensitization whereas they did not decrease inflammatory reaction when
      administered during challenge. Conversely, mitoxantrone, and cyclophosphamide,
      given as a single injection at the time of sensitization or challenge, completely
      inhibited the reaction, a property associated with T and B cell depletion. The
      data indicate that antimetabolites which are cell cycle dependent inhibit clonal
      expansion and subsequent differentiation of cytotoxic CD8+ T cells. Their lack of
      effect at the time of challenge indicates that T cell proliferation is not
      required for the expression of effector or regulatory T cell activation.
      Conversely lymphoablative drugs can inactivate or destroy differentiated
      cytotoxic T cells with rapid kinetics.

PMID- 14721774
TI  - Sequential immunohistochemical study of depigmenting and repigmenting minigrafts
      in vitiligo.
AB  - The initial steps of melanocytic dysfunction in vitiligo are hitherto not well
      understood. The aim of the present study was to examine the sequence of early
      events that occur in melanocytes after autologous minigrafting in patients with
      vitiligo, depending on their clinical response. Six patients with non-segmental
      widespread vitiligo were included in the study. Specimens of vitiliginous lesions
      were used as preoperative controls and sequential punch biopsies were taken from
      the grafted areas on days 14, 17, 21 and 28 after minigrafting.
      Immunohistochemical stains using the MoAbs HMB-45, CD4, CD8, ICAM-1, and LFA-1
      were performed in all biopsies and the labelled cells were counted by a digital
      image analyser. Results obtained show that in vitiligo patients not responding to
      minigrafting, significant numbers of cytotoxic T-lymphocytes and LFA-1 positive
      infiltrating cells occur in early phases (p < 0.05), suggesting that a cell
      mediated immune response takes place towards the grafted melanocytes. Possibly
      this cell-mediated mechanism causing unresponsiveness to minigrafts may also play
      a role in the pathogenesis of vitiligo.

PMID- 14721775
TI  - The comparison of expression of cutaneous lymphocyte-associated antigen (CLA),
      and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions
      of adult T-cell leukemia/lymphoma.
AB  - Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T
      cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1).
      In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial.
      In the present study, to discriminate MF and cutaneous lesion of ATLL using
      immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both
      disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on
      epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were
      negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma
      cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma
      cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not
      in any MF cases. OX40 was expressed in the large transformed cell population in
      both disorders. These findings suggest that CLA and ST2 could be potentially
      useful immunohistochemical markers for discrimination of mycosis fungoides and
      cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker
      for the histopathological progression of both disorders.

PMID- 14721776
TI  - ARS Component B: structural characterization, tissue expression and regulation of
      the gene and protein (SLURP-1) associated with Mal de Meleda.
AB  - The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non
      glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a
      soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations
      have been implicated in Mal de Meleda. In this study we show by
      immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the
      protein product of the ARS Component B gene) is localized to human skin,
      exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes
      underlying the stratum corneum are highly positive for SLURP1 immunostaining and
      cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is
      detected in human plasma and urine. In the mouse, expression is evident in skin,
      eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA
      expression is regulated by retinoic acid, epidermal growth factor and interferon
      gamma. The tissue localization and the association with Mal de Meleda suggest
      that ARS Component B and its protein product SLURP1 are implicated in maintaining
      the physiological and structural integrity of the keratinocyte layers of the
      skin.

PMID- 14721777
TI  - Face and body sponges: beauty aids or potential microbiological reservoir?
AB  - Small natural or synthetic sponges are commonly used in daily hygiene and in
      removing make-up. In our study we try to assess the role of sponges as reservoirs
      and vehicles in the transmission of potentially pathogenic bacterial species. We
      demonstrate that numerous Gram-negative and Gram-positive bacterial species are
      detectable in sponges after normal use by the healthy population. The most common
      bacteria to be found are Staphylococcus epidermidis, Staphylococcus aureus and
      Escherichia coli in both cellulose and nylon sponges; this observation supports
      the idea that the environmental factors (humidity, temperature) favour bacterial
      growth more than the different materials the sponges are made of. Sponges should
      be restricted to personal use, regularly washed, completely dried and kept in a
      dry place.

PMID- 14721778
TI  - Skin weathering and ashiness in black Africans.
AB  - Ashiness describes a common physiological skin condition that may develop in
      people with dark skin complexion. Environmental influences, particularly cold and
      dry weather, seem obvious. This condition has seldom been studied so far. In the
      present study, skin ashiness was assessed in 37 black African women by means of
      colorimetric assessments and xerosis ratings. Colour changes were measured by the
      parameters a* and the individual typology angle ITA degrees. Xerosis was assessed
      by visual inspection, the ultraviolet light-enhanced visualization (ULEV) method,
      and the cyanoacrylate skin surface stripping (CSSS) method. The assessments were
      performed on ashy skin of the legs and on the normal looking forehead during the
      winter season. Ashy skin was lighter but not erythematous. The ITA-revealed
      colour changes were correlated with xerosis severity as assessed by dry
      dermoscopy and by the ULEV and CSSS methods. In conclusion, ashiness due to skin
      weathering does not appear to be related to mild inflammation. It corresponds to
      a peculiar type of xerosis with reduction in Fresnel reflection by the stratum
      corneum.

PMID- 14721779
TI  - Pemphigus vegetans presenting as acrodermatitis continua suppurativa.
AB  - The authors present a 51-year-old patient with clinical signs of acrodermatitis
      continua suppurativa of the toes. Since histological findings failed to
      unambiguously support the diagnosis of acrodermatitis continua suppurativa,
      immunohistology was performed. The results showed intercellular epidermal
      fluorescence. The subsequent clinical picture (vegetating formation), the
      repeated histological examination (suprabasal cleft and eosinophilia), as well as
      the data of immunohistological findings supported the diagnosis of pemphigus
      vegetans Hallopeau. The patient was treated successfully with a combination of
      cyclosporine-A and low-dose steroid therapy. The case is of special interest,
      because there is only a single publication about phalangeal and nail involvement
      in Hallopeau's type pemphigus vegetans in the dermatological literature according
      to our knowledge.

PMID- 14721780
TI  - Kaposi's sarcoma of the glans penis in an immunocompetent patient.
AB  - We report a 39-year-old HIV negative man with a solitary reddish-brown papule
      located on the glans penis, which had developed 6 months previously.
      Histopathologic examination showed spindle-shaped cells scattered between
      collagen bundles and intermingled with small, pointed vascular-like spaces.
      Spindle-shaped cells stained positively for antiFactor VIII and anti-CD34
      antibodies. Human herpes virus-8 DNA was detected in tumor tissue and in
      peripheral blood mononuclear cells. Based on clinicopathologic and molecular
      findings, the diagnosis of classic Kaposi's sarcoma was made. Two months after
      the initial observation, three additional papules developed on the glans penis.
      Histopathologic examination of one lesion confirmed the diagnosis of classic
      Kaposi's sarcoma. The remaining lesions were treated with electrodessication and
      curettage. After a follow-up period of 6 months no evidence of recurrence was
      observed. We report this case for the unusual localization of Kaposi's Sarcoma in
      a young, HIV-negative patient.

PMID- 14721781
TI  - Nevus lipomatosus cutaneous superficialis with perifollicular fibrosis.
AB  - Nevus lipomatosus cutaneous superficialis (NLCS) is a rare hamartomatous skin
      lesion histopathologically characterized by the presence of mature fat tissue
      even within the upper dermis. Clinically, two types of NLCS can be distinguished;
      a multiple type and a solitary type. We here report a 10-month-old girl showing
      multiple type NLCS as a collection of a nodule and papules on her right abdomen.
      Histological examination revealed that the lesion was composed of a lobular
      proliferation of fat tissue throughout the dermis and immature hair follicle-like
      structures with perifollicular fibrosis. Histological alterations of the dermal
      connective tissue components were also seen, including thickening of collagen
      bundles and increased numbers of both fibroblasts and blood vessels. This is the
      first reported case of NLCS with perifollicular fibrosis.

PMID- 14721782
TI  - Necrotizing varicella zoster virus folliculitis.
AB  - Although the usual clinical features of the varicella zoster virus (VZV)-induced
      lesions are readily recognized, the same virus is also responsible for a series
      of atypical lesions. A patient is presented with a single large infiltrated
      plaque on the abdomen. Although histology showed a necrotizing folliculitis
      surrounded by a dense perifollicular inflammatory infiltrate, the clinical
      presentation was not suggestive of folliculitis. Subtle cyto-histological clues
      for viral infection were suggested. Immunohistochemistry revealed the presence of
      VZV in the remnants of the follicular structures. This report underlines one of
      the protean clinical presentations of VZV skin infections and highlights the
      discreteness of typical VZV-related cyto-histological alterations. Complementary
      VZV identification methods such as immunohistochemistry, are helpful in order to
      increase the diagnostic accuracy of unusual VZV lesions.

PMID- 14721783
TI  - Topical tacrolimus in the treatment of localized scleroderma.
AB  - Although the cause of localized scleroderma is unknown, an autoimmune mechanism
      is suspected. We describe two patients with localized scleroderma treated with
      topical tacrolimus, an immunosuppressive macrolide antibiotic. Topical tacrolimus
      0.1% ointment applied twice daily under occlusion led to a significant clinical
      improvement of late sclerotic lesions and complete clearance of early
      inflammatory skin lesions in 3 months. These were the first cases of successful
      topical tacrolimus therapy in localized scleroderma and should be regarded as a
      promising treatment option for LS, especially on account of its high tolerability
      that permits prolonged use without side-effects.

PMID- 14721784
TI  - Chordoma cutis.
AB  - We report a case of an 85-year-old white man with a diffuse form of psoriasis,
      who showed a large asymptomatic subcutaneous tumour in the sacrococcygeal region.
      On cut section there was a subcutaneous neoplasia with a glistening, friable
      surface. Histologically, the deep dermis was infiltrated by cords and nests of
      pleomorphic cells embedded in an abundant mucinous stroma, and characteristic
      physaliphorous (multivacuolated) cells were observed. The neoplastic cells were
      immunohistochemically positive for cytokeratins (using CAM 5.2 and AE1/AE3),
      vimentin, S100 protein, and epithelial membrane antigen (EMA), but negative for
      carcinoembryonic antigen (CEA). Histological and immunohistochemical findings led
      us to the diagnosis of classic chordoma. Chordomas are rare, slow growing
      malignant tumours of the spinal axis originating from remnants of the notochord.
      Occasionally, a skin lesion is the first sign of a primitive or metastatic
      chordoma.

PMID- 14721785
TI  - Videodermatoscopy improves the clinical diagnostic accuracy of multiple clear
      cell acanthoma.
AB  - A 69-year-old male presented with about 20 reddish, sharply circumscribed, smooth
      papules, 5-10 mm in diameter, sometimes with a peripheral scaling collarette,
      scattered on the legs, which appeared during the last 5 years. Videodermatoscopic
      examination showed a similar pattern in all lesions, consisting of symmetrical
      and homogeneous pinpoint-like vascular structures which tended to be arranged in
      a net-like pattern. At higher magnification each vascular structure appeared to
      have a bush-like aspect. On the basis of past medical history, clinical and
      dermatoscopic features, the diagnosis of multiple clear cell acanthoma (CCA) was
      considered. Histologic examination of a papular lesion confirmed the diagnosis.
      In conclusion, although the dermatoscopic pattern of CCA is not specific,
      videodermatoscopy may improve the clinical diagnosis of single or multiple CCA,
      ruling out clinically similar disorders that do not show the same dermatoscopic
      vascular pattern of CCA.

PMID- 14721786
TI  - Chronic indurated ulceration of the leg, epithelioid sarcoma with lymph node
      metastasis.
AB  - Epithelioid sarcoma is a seldom seen tumor characterized by an innocuous
      presentation of a non tender nodule or cluster of nodules located on a distal
      extremity with a high propensity for nodal spread as well as relentless local
      progression. We describe a patient with the neoplasm masquerading as chronic leg
      ulcers of unknown origin with an unusual immunohistochemical profile. The
      difficulty of timely clinical and histological diagnosis is a key problem
      encountered. Better awareness may result in earlier diagnosis and improved
      prognosis.

PMID- 14721787
TI  - Persistent subcutaneous Scedosporium apiospermum infection.
AB  - We report the case of a 52-year-old male heart transplant recipient with a
      persistent localized subcutaneous infection by Scedosporium apiospermum. This
      form differs from the most common mycetoma by the absence of granules. The
      patient showed multiple nodules on the right hand that were surgically removed.
      Concomitantly, he received oral itraconazole, but the infection persisted for two
      years, and several surgical interventions were necessary to eradicate the
      infection. Our case demonstrates that a medical approach alone may be not
      sufficient to cure this fungal infection.

PMID- 14721788
TI  - Pyoderma gangrenosum first presenting as a recalcitrant ulcer of the ear lobe.
AB  - A 59-year-old Japanese man with pyoderma gangrenosum occurring at the unusual
      location of the ear lobe is herein reported. The patient was not associated with
      any other systemic diseases and had suffered from chilblains at the same site for
      ten years before the ulcer appeared. The ulcer followed the development of a
      purpuric exudative lesion and had neither an undermined nor a surpiginous border
      in the early lesion. It gradually increased in size after various conservative
      treatments, recurred within a month after being excised and became aggravated
      after the administration of potassium iodide. Repeated histopathology of the
      ulcer revealed a mixed inflammatory cell infiltrate with abscesses and an
      extravasation of red blood cells in the whole dermis, without showing
      leukocytoclastic vasculitis. A culture of the excised tissue yielded no growth.
      Laboratory tests were not specific and c-ANCA was also negative. The ulcer of the
      ear did dramatically respond to systemic predonisolone of 40 mg/day. The
      auricular and periauricular area are quite rare anatomical sites of this disease
      and the difference between pyoderma gangrenosum and cutaneous Wegener's
      granulomatosis is also discussed.

PMID- 14721789
TI  - Severe nail changes due to Docetaxel treatment.
AB  - We report a case of severe nail changes which occurred in a patient under
      docetaxel treatment for metastatic breast cancer.

PMID- 14721790
TI  - Paradominant inheritance of twin spotting: phacomatosis pigmentovascularis as a
      further possible example.

PMID- 14721792
TI  - Specialty under attack: where is cardiac surgery heading?

PMID- 14721793
TI  - Off-pump coronary artery bypass grafting attenuates postoperative bleeding
      associated with preoperative clopidogrel administration.
AB  - BACKGROUND: Clopidogrel is being increasingly administered as primary therapy for
      acute coronary syndromes and prior to planned percutaneous coronary intervention
      (PCI). In these settings, surgical revascularization results in signifi- cantly
      increased postoperative bleeding, transfusion, and reexploration. Off-pump
      coronary artery bypass grafting (OPCAB) may decrease the extent of postoperative
      bleeding in patients exposed to clopidogrel. METHODS: The cases of 78 consecutive
      patients undergoing OPCAB by a single surgeon were retrospectively analyzed, and
      the patients were divided into 2 groups, those with immediately preoperative
      clopidogrel exposure (clopidogrel OPCAB, n = 15) and those without (control
      OPCAB, n = 63). Multiple perioperative parameters were statistically compared.
      The clopidogrel OPCAB group also was compared with a group of previously
      described on-pump coronary bypass patients who made up a historical control group
      (n = 59). RESULTS: Postoperative bleeding, transfusion requirements,
      reexploration rates, duration of mechanical ventilation, and length of stay were
      markedly less for clopidogrel OPCAB patients than for historical controls and
      were statistically equivalent to those of control OPCAB patients. CONCLUSION:
      Among these 15 OPCAB patients with immediately preoperative administration of
      clopidogrel and aspirin, outcome was improved compared with published results for
      on-pump coronary bypass patients and was equivalent to results among OPCAB
      patients not exposed to clopidogrel. Published, recommended approaches to
      clopidogrel administration, such as avoidance of pre-PCI clopidogrel, delay of
      surgery, and platelet transfusion do not appear to be necessary with OPCAB.

PMID- 14721794
TI  - Platelet function after off pump coronary surgery.
AB  - BACKGROUND: Little is known about the impact of off pump coronary artery bypass
      (OPCAB) on platelet function. Although improved platelet function may decrease
      bleeding and reduce cerebral and pulmonary damage, there is a concern that
      changes in platelet function may also accentuate bypass graft occlusion or other
      thrombotic processes. In this pilot study we used a point-of-care test-
      Hemostatus (Medtronic, Minneapolis, MN, USA)--to assess changes in platelet
      function after OPCAB. METHODS: We analyzed data from 11 adult patients undergoing
      CAB surgery whose platelet function was assessed before and after OPCAB. A
      Hemostatus test was conducted prior to heparin administration and after protamine
      reversal. RESULTS: There was a significant improvement in platelet function as
      measured in both channels 5 and 6 of the Hemostatus test. Blood loss was 598 +/-
      244 mL in the first 24 hours. One patient received blood products. CONCLUSION:
      This pilot study suggests that platelet function is not diminished but instead is
      improved after OPCAB. This improvement may be due to the release of newer, larger
      platelets from the bone marrow into the circulation. This finding has important
      implications for the use of antiplatelet agents perioperatively. Furthermore,
      more detailed studies in this field are needed.

PMID- 14721795
TI  - A feasibility study of the safety and efficacy of a combined clopidogrel and
      aspirin regimen following off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: Effective antiplatelet therapy may decrease the risk of complications
      following off-pump coronary artery bypass surgery (CABG). We prospectively
      evaluated the safety and early efficacy of a combined regimen of clopidogrel and
      aspirin starting immediately after off-pump CABG. METHODS: One hundred thirty
      five consecutive off-pump CABG patients received clopidogrel (75 mg/day) and
      aspirin (325 mg/day) orally or initially through a nasogastric tube for 3 months,
      commencing within 6 hours of surgery. Additionally, heparin (10,000 IU/day) was
      given subcutaneously during the first 4 postoperative days. Clinical events,
      including death, myocardial infarction (MI), reintervention, angiographically
      documented graft occlusion, stroke, pulmonary embolism (PE), deep vein thrombosis
      (DVT), and hemorrhagic events, were recorded. All patients were followed up for 3
      months. RESULTS: Thirteen of 135 off-pump CABG patients had treatment
      discontinued before discharge because of refractory atrial fibrillation requiring
      warfarin sodium (Coumadin) (6 patients), gastrointestinal bleeding (1 patient),
      DVT (1 patient), PE (1 patient), and death (4 patients). The remaining patients
      were followed up for 3 months. At 1 month, the incidences of the following events
      were: 3.0% cerebrovascular accidents (3 strokes and 1 transient ischemic attack),
      3.0% MI, 0.7% DVT, and 0.7% hemothorax. At 3 months, no additional events had
      occurred except for 1 patient developing DVT and 2 additional patients developing
      MI. Coronary angiography was indicated in these last 2 patients. All grafts were
      found to be patent. However, a native vessel required percutaneous intervention
      (stenting) in one of these patients. CONCLUSIONS: Early administration of a
      combined regimen of clopidogrel and aspirin following off-pump CABG is safe and
      is associated with a relatively low incidence of major adverse cardiac events,
      bleeding, PE, and DVT. Consequently, its routine administration after off-pump
      CABG is recommended.

PMID- 14721796
TI  - A radiofrequency modified maze and valve procedure through a port-access
      approach.
AB  - BACKGROUND: The aim of the study was to assess the feasibility and effectiveness
      of the irrigated radiofrequency modified maze procedure through a port-access
      approach during mitral valve surgery. METHODS: Forty-three patients with atrial
      fibrillation (AF) and mitral valve disease underwent a combined procedure through
      a port-access approach. The indication was a history of continuous AF for more
      than 6 months in patients eligible for minimally invasive mitral valve surgery.
      RESULTS: The incidence of early mortality was 1 patient (2.3%), and that of
      freedom from AF was 100% at the end of the operation (70% of patients with normal
      sinus rhythm, 30% with a pacemaker). One patient (2.3%) required permanent
      pacemaker implantation after surgery. One patient (2.3%) required reoperation for
      bleeding. There were no reoperations for failed valve repairs. The incidences of
      freedom from AF were 87% and 92% at 6 and 12 months, respectively. At 12 months,
      functional capacity had improved significantly (P < .05). There were no procedure
      related complications. No thromboembolic events were detected during follow-up.
      CONCLUSION: The port-access approach provided a good access for both valve
      surgery and the radiofrequency maze procedure. The combination of direct and
      videoscopic vision allowed an adequate view and led to a safe and efficient
      combined procedure. Short- and intermediate-term follow-up results were
      favorable.

PMID- 14721797
TI  - Coronary artery bypass graft with minimal extracorporeal circulation.
AB  - BACKGROUND: To evaluate the advantages and benefits of a minimized extracorporeal
      circulation system in the performance of coronary artery bypass grafts. METHODS:
      From September 2000 to February 2003, 279 consecutive patients underwent isolated
      coronary artery bypass grafting with minimal extracorporeal circulation. A group
      of 243 patients at good risk as defined by a Euro- SCORE of 3 underwent complete
      bypass and blood cardioplegia, and a high-risk group of 45 patients (EuroSCORE,
      6) underwent operations with partial assistance and a beating heart. In a
      prospective substudy analysis of thrombocyte and platelet counts, transfusion
      requirements, PaO2/FIO2, leukocyte count, C-reactive protein level, postoperative
      bleeding, intensive care unit stay, and ventilation, 40 patients from the good
      risk group were matched and compared with 40 patients who underwent operations
      with a conventional extracorporeal system. RESULTS: Revascularization was
      complete with a mean of 2.8 distal anastomoses in the good-risk group and 2.4 in
      the high-risk group. Mortality rates were 1.2% and 4%, respectively. The system
      provided either complete or partial bypass assistance and depended on preload and
      afterload. The system also allowed easy access to all territories with perfect
      hemodynamic stability. Priming was reduced to 400 mL, and arterial and venous
      saturation monitoring revealed excellent maintenance of pH values. No
      complications or failure of the system occurred. Hemodilution, inflammatory
      response, and transfusion requirements were reduced in the minimal extracorporeal
      circulation group. CONCLUSIONS: Minimal extracorporeal circulation allows minimal
      hemodilution and reduces transfusion requirements. The method allows safe and
      complete revascularization of either an arrested or a beating heart.

PMID- 14721798
TI  - A miniature right heart support system improves cardiac output and stroke volume
      during beating heart posterior/lateral coronary artery bypass grafting.
AB  - BACKGROUND: Certain heart manipulations carried out to access anastomotic sites
      during beating heart coronary artery bypass (OPCAB) compromise hemodynamics, and
      these risks can affect end-organ perfusion and limit patient selection. Evidence
      suggests that right heart support (RHS) augments left ventricular preload and
      provides hemodynamic stability. This study evaluated hemodynamic measures in
      OPCAB with RHS with respect to individual target vessels and general target
      distribution groups. METHODS: Beating heart surgery was performed on 52 patients
      with left ventricular preload managed with RHS. The average patient age was 69.9
      years, and the average ejection fraction was 42.9% +/- 10.9%. Measurements of
      cardiac output, stroke volume, mean arterial pressure (MAP), heart rate, and
      cardiac index (CI) were taken at baseline, during each anastomosis with the
      optimal heart position, and when the RHS was momentarily interrupted prior to
      heart release. Anastomoses were categorized individually and into
      posterior/lateral (n = 91) or anterior/right (n = 90) groups and divided into the
      following output groups based on CI with optimal heart positioning without RHS:
      group 1 (low output; CI < 1.8), group 2 (marginal output; 1.8 < or = CI < 2.2),
      group 3 (acceptable output; CI > or = 2.2), and group 4 (output unchanged or
      increased). RESULTS: One hundred eighty-one vessels were grafted with an average
      of 3.5 per patient. Significant reductions in CI, MAP, and stroke volume were
      observed for all target vessels when RHS was briefly off, especially for
      posterior and lateral target vessels (12%-26% decrease). In both
      posterior/lateral and anterior/right target vessel groups, RHS improved CI and
      MAP in > or = 90% of the anastomoses (groups 1-3). Without RHS, 60% of
      posterior/lateral and 54% of anterior/right target positions resulted in
      critically low or marginal output (groups 1 and 2). There was one bypass
      conversion and no surgical interruptions, intraoperative intra-aortic balloon
      pump placements, or deaths. CONCLUSION: Augmenting left ventricular preload with
      RHS improves hemodynamic measures during OPCAB for all target vessel positions
      and provides critical support in a large number of anastomoses.

PMID- 14721799
TI  - Totally minimized extracorporeal circulation: an important benefit for coronary
      artery bypass grafting in Jehovah's witnesses.
AB  - BACKGROUND: Jehovah's Witnesses who require cardiac surgery represent a challenge
      to the physician because of their refusal to accept blood transfusions. Because
      coronary artery bypass grafting (CABG) is performed by most surgeons under
      cardiopulmonary bypass (CPB), which has potentially deleterious effects on
      hemostasis, we used a new concept called minimal extracorporeal circulation
      (MECC). MECC includes heparin-coated tubing, a centrifugal pump, and an
      oxygenator. There is no venous reservoir or vent, and suction is used through the
      cell saver. We assessed the hypothesis that MECC in combination with low-volume
      blood cardioplegia preserves more hemoglobin than conventional CPB in standard
      CABG. METHODS: In 40 patients of the Jehovah's Witnesses faith undergoing CABG
      with the use of MECC and intermittent warm blood cardioplegia, clinical and
      biological data as well as values for parameters of hemolysis (plasma hemoglobin)
      and myocardial damage (troponin T) were determined. The results were compared
      with those of a control group of 40 patients who underwent operations with
      standard CPB. RESULTS: Demographics, hemodynamics, the number of anastomoses, and
      CPB and cross-clamp times were comparable between the groups. MECC patients
      demonstrated significantly lower peak levels of plasma hemoglobin (21.8 +/- 114
      mg/dL versus 35.4 +/- 15 mg/dL) and troponin T (0.12 +/- 0.4 ng/mL versus 0.65 +/
      0.7 ng/mL), a higher minimum hematocrit level during CPB (30% +/- 7% versus 23%
      +/- 6%), and a higher hemoglobin level 2 days after surgery (13 +/- 3 g/100 mL
      versus 9.4 +/- 0.98 g/100 mL). Preoperative values were not significantly
      different. CONCLUSION: The use of MECC instead of conventional CPB reduces
      hemolysis, hemodilution, blood loss, and myocardial damage.

PMID- 14721800
TI  - PRECiSe (priming reduced extracorporeal circulation setup): results of a safety
      study.
AB  - BACKGROUND: Different low-priming systems limited to coronary artery bypass
      grafting (CABG) have been introduced. We describe the priming reduce d
      extracorporeal circulation setup (PRECiSe), a new low-priming system that
      supplies all of the features of cardiopulmonary bypass. METHODS: PRECiSe
      incorporates the DeltaStream diagonal pump, which pumps blood from the right
      atrium to the aorta via a membrane oxygenator and a filter. The system is placed
      beneath the patient's head, resulting in extremely short tubing lengths. A
      reservoir allows the use of suckers and vents. Autologous blood priming further
      reduces hemodilution. RESULTS: In the safety study, the system was used for
      extracorporeal circulation in 11 patients undergoing CABG without the occurrence
      of any adverse events. By using the PRECiSe system, we reduced the mean priming
      volume to 268.5 mL, resulting in minimal hemodilution and transfusion
      requirements. CONCLUSION: The use of PRECiSe for extracorporeal circulation in
      CABG is safe and reduces priming volume as well as transfusion requirements.
      Further studies are necessary to investigate the clinical benefit for patients as
      well a s the use of the system in open heart procedures.

PMID- 14721801
TI  - Improved survival with ventricular assist device support in cardiogenic shock
      after myocardial infarction.
AB  - BACKGROUND: Cardiogenic shock after acute myocardial infarction is associated
      with a very high mortality rate. METHODS: A retrospective review was performed of
      records of all patients supported with an Abiomed device at our institution
      between 1994 and 2002 to identify those patients who underwent device insertion
      for the treatment of acute myocardial infarction complicated by cardiogenic shock
      (AMI-CS). RESULTS: Seventeen patients who were suffering from AMI-CS and for whom
      medical management was failing were supported using the Abiomed BVS 5000. The
      average age of these patients was 57.6 years. Eleven patients were suffering
      primarily from left ventricular dysfunction and were supported with a left
      ventricular assist device (LVAD). Eight of these patients were weaned from device
      support, a nd 6 survived to hospital discharge (54%). In contrast, 6 patients
      presented with biventricular failure and were supported with biventricular VADs
      (BiVADs). None of these BiVAD patients could be weaned from device support. Two
      BiVAD patients underwent cardiac transplantation, and only one survived.
      CONCLUSION: In the presence of left ventricular failure producing cardiogenic
      shock after myocardial infarction, LVAD support can produce a 54% survival rate
      in those patients w ho are failing medical management. However, in patients in
      biventricular failure after myocardial infarction, BiVAD support may be used to
      stabilize the patient until transplantation, but the overall prognosis remains
      poor.

PMID- 14721802
TI  - Surgical treatment of heart failure in patients with primary and ischemic dilated
      cardiomyopathy.
AB  - OBJECTIVE: The aim of this study was to show hemodynamic and clinical improvement
      of heart failure after reductive annuloplasty of double (mitral and tricuspid)
      orifices (RADO) in the treatment of ischemic (IDCM) and primary (PDCM) dilated
      cardiomyopathy. MATERIALS AND METHODS: From November 1986 to July 15, 2002, 341
      patients underwent operations for dilated cardiomyopathy. The IDCM group
      consisted of 231 patients (68%) with a mean ejection fraction (EF) of 23.3%. From
      July 1991 to July 15, 2002, the 110 patients in the PDCM group (mean EF, 22.9%)
      underwent such operations. RESULTS: The postoperative 30-day mortality rate was
      5.9% for the entire patient population, 7.3% for the IDCM group, and 2.7% for the
      PDCM group. Follow-up survival rates were 61.5% +/- 4.0% at 5 years and 38.2% +/-
      8.0% at 14 years for the IDCM group and 43.9% +/- 5.6% at 5 years and 21.3% +/-
      8.5% at 10 years for the PDCM group. CONCLUSION: RADO corrects remodeling of the
      fibrous skeleton of the heart, changes the spherical geometry of the left
      ventricle, improves the hemodynamic action of the left and right ventricles, and
      slows down the progression of heart failure. We recommend the RADO procedure as
      an important associated procedure in the surgical treatment of IDCM and as a new
      surgical alternative for treating the early stage of PDCM immediately after the
      first decompensation.

PMID- 14721803
TI  - Improved patient outcomes when transmyocardial revascularization is used as
      adjunctive revascularization.
AB  - BACKGROUND: Transmyocardial revascularization (TMR) has been recently used to
      treat patients with angina for whom angioplasty/stenting and/or coronary artery
      bypass grafting (CABG) is no longer an option. METHODS: A retrospective review of
      255 consecutive patients who required CABG was done. Group 1 patients (n = 219)
      underwent complete revascularization with CABG alone. Group 2 patients (n = 36)
      received CABG plus TMR. TMR was performed in regions of nongraftable coronary
      targets. Indications for surgery in both groups were Canadian Cardiovascular
      Society angina scores III or IV and an ejection fraction > or = 30%. Exclusion
      criteria were an emergency procedure within 12 hours, unstable angina, or an
      acute myocardial infarction within 72 hours. Thirty-day outcomes of the two
      groups were compared. The means +/- SD of patient ages (63.3 +/- 1.6 years versus
      65.4 +/- 1.4 years) and ejection fractions (51.6% +/- 0.9% versus 48.5% +/- 1.6%)
      were similar for the two groups. RESULTS: The number of grafts performed and
      operating room times for the two groups were similar (3.1 +/- 0.1 versus 2.9 +/-
      0.1 and 276.7 +/- 4.4 minutes versus 272.3 +/- 10.7 minutes, respectively).
      Intensive care unit times and lengths of stay (emergency room to discharge) were
      significantly shorter in the CABG plus TMR group (2.1 +/- 0.2 days versus 1.6 +/-
      0.2 days [P < .001] and 8.2 +/- 0.4 days versus 7.1 +/-0.6 days [P < .001],
      respectively). The 30-day readmission rate was lower in the CABG plus TMR group
      (7.8% versus 2.8%; P < .5). The frequency of atrial fibrillation was also
      significantly lower in the CABG plus TMR group (37.4% versus 16.7%; P < .025).
      Major adverse outcomes, such as reoperation for bleeding, respiratory failure,
      renal failure, stroke, and mortality were similar in the two groups, although
      there were no mortalities in the CABG plus TMR group. CONCLUSION: TMR as an
      adjunctive revascularization to CABG in selected patients with limited options
      may improve in-hospital outcomes.

PMID- 14721804
TI  - Primary OPCAB as a strategy for acute coronary syndrome and acute myocardial
      infarction.
AB  - BACKGROUND: Conventional coronary artery bypass graft (CABG) surgery using
      cardiopulmonary bypass (CPB) carries higher mortality and morbidity for patients
      undergoing surgery during acute coronary syndrome (ACS). The aim of this
      retrospective study was to evaluate potential benefits of avoiding CPB by instead
      performing off-pump CAB (OPCAB) during surgery on patients in ACS. METHODS: Among
      624 patients who underwent OPCAB between January 1999 and June 2001, 143
      underwent surgery during ACS (group 1). The ACS patients in group 1 were divided
      into 2 subgroups: 66 underwent surgery during acute myocardial infarction (AMI
      group) and 77 during unstable angina classified as class III or IV according to
      the Braumwald classification (unstable coronary artery disease [CAD] group).
      Group 2 (the elective CAD group) consisted of 481 patients who underwent isolated
      elective OPCAB during the same time period. RESULTS: Overall 30-day mortality was
      4.9% (n = 7) for the ACS group and 0.83% (n = 4) for the elective CAD group (P <
      .0001). Differences between groups were found in use of inotropes, intraaortic
      balloon pump, and subsequent conversion of OPCAB to CPB (P < .0001, P < .01, and
      P < .03, respectively), as well as use of blood transfusion (P < .0003).
      Multivariate logistic regression analysis for 641 patients revealed ACS (P <
      .015), AMI (P < .019), renal failure (P < .017), and left ventricle aneurysm (P <
      .028) as independent risk factors for 30-day mortality in ACS reoperation (P =
      .02), whereas in AMI renal failure (P = .02) appeared to be an independent risk
      factor. CONCLUSIONS: OPCAB is a valuable treatment strategy in ACS patients;
      however, it carries significant mortality and morbidity. Careful preselection and
      timing of intervention are required in order for patients to fully benefit from
      the OPCAB strategy.

PMID- 14721805
TI  - Beating heart revascularization using only bilateral internal thoracic arteries
      for triple-vessel disease: early angiographic findings.
AB  - BACKGROUND: Early postoperative coronary angiography was performed to establish
      the feasibility of treating patients with triple-vessel disease by performing
      completely arterial revascularization on the beating heart using only bilateral
      internal thoracic arteries (ITAs). METHODS: Between March 2001 and February 2003,
      113 patients with triple-vessel disease (age, 62.0 +/- 8.6 years) underwent
      beating heart revascularization using only the bilateral ITAs. Left ventricular
      ejection fractions ranged from 23% to 78% (mean, 51.3% +/- 15.1%). The incidence
      of diabetes mellitus was 46%. Early postoperative coronary artery angiographic
      follow-up was performed since May 2002 in the last 59 sequential patients.
      RESULTS: There were no operative deaths. Perioperative myocardial infarction and
      postoperative low cardiac output occurred in only 1 patient each. The mean number
      of distal anastomoses was 3.9 +/- 0.7 per patient. The patency rates were 100%
      for the left ITA and 98.1% for the right. Competitive flow patterns were present
      in 25 distal anastomosis sites (10.5%). A multivariate analysis showed that the
      degree of stenosis (<75%), the extent of focal stenosis of the native coronary
      artery, and the intraoperative transit-time flow rate (<10 mL/min) were the
      statistically significant risk factors for competitive flow. CONCLUSION: This
      surgical strategy is feasible, is safe, and yields good early angiographic
      outcomes, even following beating heart revascularization. However, in less
      significant lesions competitive flow patterns were relatively prevalent, so this
      technique might be reserved until it is proven to provide good long-term patency
      and function.

PMID- 14721806
TI  - Technical aspects of harvesting the radial artery with the harmonic scalpel.
AB  - BACKGROUND: Harvesting the radial artery (RA) with ultrasonic dissection with the
      Harmonic Scalpel reduces spasm induced by surgical handling. Topical exposure to
      phentolamine methanesulphonate (Regitine) exerts an additional effect of
      vasodilatation. METHODS: Between January and December 2002, the RA was harvested
      as a pediculated vessel with the Harmonic Scalpel in 145 consecutive patients
      undergoing myocardial revascularization. A fasciotomy of the pedicle was
      performed after harvest ing. A composite graft with the reverse free RA on the in
      situ left internal thoracic artery (ITA) was prepared before the construction of
      distal coronary anastomoses. The RA was then placed in a syringe filled with
      Regitine (0.07 microg/mL) for 10 minutes. ?par RESULTS: The mean number of
      grafts/patient was 3.0. The mean number of RA anastomoses was 2.0/patient. Left
      ITA free flow was 105 +/- 34 mL/min. Regitine increased the RA free flow from 60
      +/- 35 mL/min to 82 +/- 30 mL/min (P <.05). Fourteen patients underwent
      postoperative coronary angiography. All RA anastomoses were patent. CONCLUSION:
      The compound effect of RA harvesting with the Harmonic Scalpel and topical
      treatment with the alpha- blocking agent Regitine increases the RA free flow and
      significantly decreases intraoperative spasticity.

PMID- 14721807
TI  - Midterm results of routine bilateral internal thoracic artery grafting.
AB  - BACKGROUND: Skeletonized dissection of the internal thoracic artery (ITA)
      decreases the occurrence of sternal devascularization, thus decreasing the risk
      of postoperative sternal complications in patients undergoing bilateral ITA
      grafting. METHODS: From April 1996 to July 1999, 1000 consecutive patients
      underwent bilateral skeletonized ITA grafting. Of the 770 male and 230 female
      patients, 420 were older than 70 years, and 312 had diabetes. RESULTS: Operative
      mortality was 3.3%. Follow-up (40-78 months) revealed 79 late deaths, and the
      Kaplan-Meier 6-year survival rate was 88%. Cox regression analysis revealed
      increased overall mortality (early and late) in patients with preoperative
      congestive heart failure (risk ratio [RR], 2.13; 95% confidence interval [CI],
      1.31-3.45), in patients with peripheral vascular disease (RR, 5.52; 95% CI, 3.31
      9.19), and in patients older than 70 years (RR, 2.18; 95% CI, 1.37-3.47). Early
      postoperative morbidity included sternal infection (2.2%), cerebrovascular
      accident (1.6%), and perioperative myocardial infarction (1%). Multiple
      regression analysis showed repeat operation (odds ratio [OR], 7.5; 95% CI, 1.77
      31.6) and chronic obstructive pulmonary disease (OR, 3.6; 95% CI, 1.27-10.75) to
      be independent predictors of sternal infection. During follow-up, angina returned
      in 95 patients, 24 of whom required reintervention (20 cases of percutaneous
      balloon angioplasty and 4 reoperations). Postoperative coronary angiography
      performed in 87 patients revealed an ITA patency rate of 91%. CONCLUSIONS:
      Bilateral skeletonized ITA grafting is associated with satisfactory early and
      midterm results. We do not recommend the use of this surgical technique in
      patients with chronic obstructive pulmonary disease.

PMID- 14721808
TI  - Myocardial revascularization using the arterial T graft: which conduit should be
      chosen for the free graft?
AB  - BACKGROUND: The T graft is achieved by the end-to-side implantation of a free
      arterial graft into the left internal thoracic artery, which remains in situ.
      Which conduit is best suited as the free graft is still being discussed. METHODS:
      Two groups of patients are compared. The right internal thoracic artery (RITA)
      was used as a free graft in group I (n = 129), and the radial artery was used in
      group II (n = 84). RESULTS: The RITA was used more often with male patients (P <
      .02) and with patients presenting a reduced left ventricular ejection fraction (P
      < .03). The average number of coronary anastomoses per patient was higher in
      group II than in group I (P < .002). There were no significant differences
      between the groups in early mortality (0.8% in group I and 1.2% in group II) and
      morbidity. Postoperative chest tube output was significantly higher in group I
      than in group II (P < .05). The mean follow-up time was 35.2 +/-28.3 months.
      There were no significant differences regarding late mortality (6.9% in group I
      and 5.3% in group II) and the recurrence of angina (group I, 6 cases or 5.5%;
      group II, 3 cases or 4.2%). Because of the recurrence of angina or questionable
      chest pain in 22 patients, angiography was performed, and results showed a
      patency rate of 90.9% in group I and 93.1% in group II. CONCLUSIONS: Based on our
      experience, we advise using the RITA as a free graft with tall men and also in
      patients with a reduced left ventricular ejection fraction, diabetes, and
      obesity. The radial artery should be used with small women if there is a high
      risk of bleeding and if several coronary anastomoses are necessary.

PMID- 14721809
TI  - A new clip device for the construction of vascular interrupted anastomoses in
      congenital cardiac surgery.
AB  - BACKGROUND: Many different mechanical vascular anastomotic devices have been
      developed recently, mostly rigid stenting mechanisms applicable only in coronary
      artery bypass grafting surgery. U-Clips, however, allow the precise construction
      of any vascular interrupted anastomosis, preserving pulsatility and perhaps
      growth potential. METHODS: We report the first use worldwide of U-Clips for
      congenital cardiac surgery in 10 pediatric patients (mean age, 2.3 +/- 1.7
      years). The operations took place between July 2001 and July 2002 for coarctation
      repair (3 patients), Glenn shunt (5 patients), Blalock-Taussig shunt (1 patient),
      and arterial switch (1 patient). RESULTS: Device handling, primary hemostasis,
      and patency were excellent, and no device-related complications occurred. Because
      of the learning curve, aortic cross-clamp times were significantly longer for the
      repair of coarctation with U-Clips than with the running-suture technique (21.7
      +/- 2.3 minutes versus 14.4 +/- 2 minutes; P = .012). Postoperative recoveries
      were uneventful in all patients except for a baby with pulmonary atresia with
      intact ventricular septum, who died after 62 days. After a mean follow-up period
      of 11.9 +/- 4.4 months, echocardiographic controls of all anastomoses showed
      nonturbulent flow without any restriction. CONCLUSION: The U-Clip device may be a
      useful adjunct in congenital cardiac surgery for facilitating the creation of
      interrupted vascular anastomoses. Further evaluation is warranted for determining
      the long-term benefits of these devices with respect to growth preservation and
      restenosis.

PMID- 14721810
TI  - U-clip anastomoses in coronary artery bypass grafting: initial clinical
      experience.
AB  - BACKGROUND: Recent studies suggest that the U-Clip interrupted coronary artery
      anastomosis is superior to continuous suture. However, clinical experience with
      this device is limited. AIM: To evaluate our initial clinical experience with the
      U-Clip technology. METHODS: Outcomes of 59 patients undergoing isolated coronary
      artery bypass grafting (CABG) using U-Clips (UCs) were compared to outcomes of
      138 patients undergoing CABG using conventional sutures (Conv). RESULTS: The
      average number of distal anastomoses was similar in the groups (UC, 2.9; Conv,
      3.2; P = .33). Also similar were the number of arterial grafts (1.6 versus 1.5, P
      = .4), percentage of sequential anastomoses (22% versus 12%, P = .058), and
      percentage performed off pump (27% versus 28%, P = .74). Cardiopulmonary bypass
      and aortic crossclamp times were longer in the UC group (98 +/- 27 versus 81 +/-
      20 minutes, P = .001; 63 +/- 25 versus 54 +/- 24 minutes, P = .028). Rates of
      operative mortality (UC, 1.69%; Conv, 0.7%), postoperative myocardial infarction
      (0% each), stroke (0% each), renal failure (2% versus 1.4%), and blood
      transfusion (53% versus 58%) were not statistically different. Average follow-up
      in 36 (61%) of UC patients was 5 +/- 2 months (range, 1-7 months). One patient
      died from a non-cardiacrelated cause. At the time of follow-up 90% of patients
      were in angina class I-II. CONCLUSIONS: The U-Clip interrupted anastomosis
      technique is versatile and safe and is associated with excellent short-term
      outcomes.

PMID- 14721811
TI  - Vettath's anastomotic obturator: a simple proximal anastomotic device.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting has been shown to improve
      the postoperative course of patients undergoing coronary artery bypass grafting
      (CABG) surgery, but the need for side-clamping the aorta to perform the proximal
      anastomosis is still a risk factor for causing neurologic injury postoperatively.
      Hence, our endeavor to fabricate an obturator to perform the proximal anastomosis
      without side-clamping the aorta is described. METHODS: From July 2002 to February
      2003, we performed more than 150 CABG surgeries in our new cardiac center, and 92
      patients had proximal saphenous vein graft anastomoses performed with Vettath's
      anastomotic obturator (VAO). RESULTS: A total of 147 CABG surgeries (98%) were
      performed on the beating heart, of which 135 (90%) were done off-pump. Early in
      our experience, the top ends were performed with side-clamping until we
      introduced our new VAO after trials on a perfused animal heart model. Ninety-two
      patients had proximal anastomoses carried out with the VAO, and 97 proximal
      anastomoses were performed on the aorta, because 5 of the patients had 2 proximal
      anastomoses. We had only one patient in our series who came back with angina
      after 3 months. Results of repeat coronary angiography with this patient showed a
      patent proximal anastomosis and no graft problems. CONCLUSION: Our initial
      results with the VAO have been excellent. We have been able to use it in all of
      our proximal anastomoses of late. With regular practice, this procedure can be
      performed with ease and can definitely avoid the neurologic deficits caused by
      side-clamping the aorta.

PMID- 14721812
TI  - An automatic sutureless coronary anastomotic device: initial results of an animal
      study.
AB  - BACKGROUND: The efficacy and long-term patency of a new distal anastomotic device
      (DAD) for the creation of rapid, sutureless end-to-side venous or arterial
      coronary artery bypass graft anastomoses were tested in a sheep model. METHODS:
      The DAD was used on the beating hearts of 34 sheep to create 20 anastomoses
      between saphenous veins (n = 9) or internal mammary arteries (n = 11) and various
      coronary arteries. Fourteen conventional hand-sutured anastomoses (7 veins; 7
      internal mammary arteries) served as controls. The sheep were sacrificed 1 day, 1
      week, and 1, 3, and 6 months after surgery. RESULTS: The immediate patencies of
      all anastomoses were proven by the rates and pattern of flow. There were no
      significant differences between the DAD and suture anastomosis groups in
      presacrifice pulsatility index and occlusion rate. The histomorphometric studies
      showed complete intimal bridging over the DAD with no significant differences
      between DAD and suture anastomoses with respect to tissue response, mural injury,
      inflammation, and adventitial fibrosis. CONCLUSIONS: The DAD enables the creation
      of rapid, efficient, and sutureless venous or arterial coronary anastomoses. The
      long-term results of histomorphometric studies show that the results with the DAD
      are comparable with those of conventional hand-sutured anastomoses.

PMID- 14721813
TI  - Intraoperative color Doppler ultrasound assessment of anastomoses of the left
      internal mammary artery to the left anterior descending coronary artery during
      off-pump coronary artery bypass surgery correlates with angiographic evaluation
      at the 8-month follow-up.
AB  - OBJECTIVE: This study was performed to evaluate the correlation between
      intraoperative color Doppler ultrasound assessment of anastomoses of the left
      internal mammary artery (LIMA) to the left anterior descending coronary artery
      (LAD) performed on the beating heart and the angiographic assessment after 8
      months. METHODS: Twenty patients (M/F ratio, 14:6; mean age, 62 +/- 8 years)
      underwent epicardial color Doppler ultrasound imaging with a 10-MHz linear array
      GE Vingmed transducer combined with a GE Vingmed System FiVe. Transit-time
      flowmetry was used as intraoperative control. Follow-up coronary angiography
      after a median of 245 days (range, 128-320 days) allowed assessment of
      thrombolysis in myocardial infarction (TIMI) flow and FitzGibbon grading in all
      patients. Detailed quantitative coronary angiography was performed in 10 patients
      with an emphasis on comparing the LAD diameter at the toe of the anastomosis (D1)
      and in the downstream LAD (D2). RESULTS: Intraoperative ultrasound analysis
      revealed 19 patent LIMA-LAD anastomoses (95%). A >50% stenosis was detected in 1
      anastomosis (5%), which was subsequently revised successfully. Follow-up
      angiographic evaluation showed TIMI-III flow and FitzGibbon grade A in 18 of 20
      anastomoses (90%). One anastomosis was occluded, and one had FitzGibbon grade B
      stenosis. The D1/D2 ratios of the LAD measurements assessed with intraoperative
      ultrasound and follow-up quantitative coronary angiography were significantly
      correlated (r2 = 0.62; P < .01). CONCLUSION: Intraoperative color Doppler
      ultrasound allows a detailed evaluation of LIMA-LAD anastomoses during off-pump
      surgery, and the results correlate significantly with those of angiographic
      evaluation after 8 months. The present study shows that epicardial ultrasound is
      a promising tool for verification of LIMA-LAD anastomoses performed on the
      beating heart and may reduce the risk of impaired graft flow caused by technical
      errors.

PMID- 14721814
TI  - Off pump long-onlay-patch angioplasty to the LAD using the left internal mammary
      artery.
AB  - Surgical treatment for diffusely diseased coronary arteries has been considered
      to be a relative contraindication for off pump coronary artery bypass (OPCAB)
      grafting. We report a case of off pump long-onlay-bypass grafting using the left
      internal mammary artery. To our knowledge, the long-onlay-patch grafting with
      OPCAB technique has not been previously described. Two sets of Octopus-3 tissue
      stabilizers were placed longitudinally along the target coronary artery (Double
      Octopus technique). This technique allowed us to performed surgical angioplasty
      and bypass grafting without cardiopulmonary bypass support. Patients with severe
      diffuse coronary lesions who are at high risk for cardiopulmonary bypass will
      benefit from this technique.

PMID- 14721815
TI  - Early postoperative acute aortic dissection, the leading cause of sudden death
      after cardiac surgery? Critical role of the computed tomography scan.
AB  - Iatrogenic acute aortic dissection (AOD) is known to occur during cardiac surgery
      or cardiac catheterization, whereas delayed AOD usually happens up to several
      years after an uneventful operation. Both entities usually are easily recognized,
      and their management is well described in the literature. Conversely, early
      postoperative AOD has not been described with any frequency in the literature,
      leading one to believe that once surgery is terminated, AOD is unlikely to occur
      and account for any early postoperative mortality or morbidity. We present our
      recent experience with 4 patients who sustained early postoperative AOD and whose
      diagnoses were facilitated by computed tomography (CT) scanning of the chest.
      Early postoperative acute AOD may not be uncommon and may account for more
      disasters and deaths than are acknowledged in the literature. Diagnosis is made
      expeditiously if such AOD is suspected and a CT scan of the chest is done.
      Prevention may be based on avoiding the manipulation of the ascending aorta and a
      tighter control of hypertension in the immediate postoperative period. The
      treatment of this AOD entity is not very difficult and is within the reach of
      every trained cardiac surgeon.

PMID- 14721816
TI  - Combined treatment of aortic type A dissection: ascending aorta repair and
      placement of a stent in the descending aorta.
AB  - BACKGROUND: The established treatment modality of acute Stanford type A
      dissection includes repairing the ascending aorta and a variable part of the
      aortic arch and leaving the descending aorta untreated. We report a simultaneous
      approach of open repair of the ascending aorta with the transluminal placement of
      a stent in the descending aorta to minimize the consequences of an untreated
      descending aorta. METHODS: Two cases of type A aortic dissection are described,
      one case with the entry port in the descending aorta and the second case with the
      entry port in the aortic arch. Both patients were treated by the replacement of
      the ascending aorta (and the aortic arch in the second case) and the placement of
      a stent in the descending aorta with a new device as the patients were under
      circulatory arrest and deep hypothermia. The device consists of a Djumbodis stent
      mounted on a compliant balloon. This stent is made of 316L stainless steel and
      can be adapted to the shape of the aortic arch or descending aorta. Three
      different lengths are available: 4 cm, 9 cm, and 14 cm. The device used in these
      patients has a diameter of 9 mm. RESULTS: The early results were satisfactory
      with a completely thrombosed false lumen in one case and a partially thrombosed
      false lumen in the other, according to immediate postoperative transesophageal
      echocardiography control. A follow-up computed tomographic chest scan was done at
      12 months in the first case and at 7 months in the second case and confirmed the
      good surgical results. CONCLUSIONS: This preliminary study shows that combined
      surgical and endovascular treatment of acute type A dissection is feasible and
      that at least partial thrombosis of the false lumen can be achieved, potentially
      minimizing the risk of further dilatation or rupture. The early results are
      encouraging, but more cases and long-term results are required to demonstrate the
      effectiveness of this new combined treatment modality.

PMID- 14721817
TI  - Early results of using the bovine jugular vein for right ventricular outflow
      reconstruction during the Ross procedure.
AB  - OBJECTIVE: To study the early function of the bovine jugular vein (BJV) when used
      for right ventricular outflow tract (RVOT) reconstruction during the Ross
      procedure. METHODS: Seventeen consecutive patients (median age, 12 years; range,
      30 days to 40 years) who had undergone a Ross procedure with RVOT reconstruction
      using a BJV were reviewed. Nine patients had prior balloon valvotomy (n = 6)
      and/or surgical aortic valvotomy (n = 4). Additional procedures included a
      reduction-plasty of the ascending aorta (5 patients), a Konno procedure (2
      patients), a mitral valve repair/replacement (2 patients), and others (3
      patients). The size of the BJV ranged from 12 to 22 mm (median, 20 mm). RESULTS:
      There were no early or late deaths. None of the patients encountered any
      significant postoperative complications. The neo-aortic valve showed good
      function in all patients with no more than trivial insufficiency. At a median
      follow-up period of 11 months, the frequency of freedom from BJV graft
      dysfunction/reintervention/reoperation was 100%. One patient had moderate
      insufficiency of the BJV in a perioperative examination that regressed to mild
      insufficiency during follow-up. Overall, none of the patients had more than mild
      insufficiency at follow-up. Four patients showed a flow acceleration of more than
      250 cm/s (equivalent to a gradient of 25 mm Hg) across the BJV, and the remaining
      patients had lower gradients. CONCLUSIONS: The BJV, when used to replace the
      pulmonary valve in the Ross procedure, showed excellent function in the early
      phase. The large size range and easy availability of this valved conduit are
      particularly attractive. Further followup is needed to determine the long-term
      results of its use.

PMID- 14721818
TI  - A single bicaval venous cannula used for optimization of endoscopic robotically
      assisted procedures of the heart.
AB  - Robotically assisted heart operation is one of the minimally invasive approaches
      that have revolutionized many surgical procedures. Robotic procedures on the
      heart, however, are by no means routine, and their optimization requires
      development of new instruments and techniques. Described here is the robotically
      assisted use in a sheep model of a new peripherally inserted bicaval venous
      cannula in the totally endoscopic closure of atrial septal defect. The exposure
      of the surgical target area was successful with no obstructions in the surgical
      view. The cannula shows sufficient flow characteristics for cardiopulmonary
      bypass. Subsequent suturing of the atrial septum defect was achieved without
      complications in the 4 experimental animals.

PMID- 14721819
TI  - New xenograft valved conduit (Contegra) for right ventricular outflow tract
      reconstruction.
AB  - BACKGROUND: The well-known flaws of existing valved conduits for reconstruction
      of the right ventricular outflow tract (RVOT) continue to stimulate research for
      the elusive "perfect" conduit. In this study, we describe our experience with a
      glutaraldehyde-treated bovine jugular vein valved conduit (Contegra). METHODS: 55
      years underwent implantation of a Contegra conduit. Diagnoses/procedures included
      repair of truncus arteriosus (2 patients), pulmonary atresia (3 patients), severe
      pulmonary insufficiency after prior repair of tetralogy of Fallot (9 patients),
      and replacement of degenerated valved conduit (1 patient). RESULTS: No operative
      deaths occurred. One patient required an early conduit replacement for
      unexplained valve thrombosis. The early postoperative mean transconduit pressure
      gradient was 7.7+/- 4.9 mm Hg. At a mean follow-up time of 18.5 +/- 6.9 months,
      all patients were asymptomatic with no discernible calcification in the valve or
      conduit or significant valve incompetence, while the mean transvalvular gradient
      remained low (11.1 +/- 4.5 mm Hg). CONCLUSION: The Contegra valved conduit is
      well suited for RVOT reconstruction, avoids the use of additional foreign
      material, and remains well functioning during early followup. Nonetheless, the
      long-term durability remains to be ascertained.

PMID- 14721820
TI  - Hemodilution during off-pump coronary artery bypass grafting: can we improve flow
      and reduce hypercoagulability?
AB  - BACKGROUND: The aim of this study was to compare intraoperative coronary graft
      flows performed on pump and off pump and to evaluate the effects of hemodilution
      on coronary graft flows in off-pump coronary artery bypass grafting (CABG)
      patients by using transit time flow measurements (TTFM). METHODS: Three hundred
      patients undergoing only CABG procedures were enrolled in a prospective
      randomized manner into 3 groups. Group 1 consisted of 100 patients undergoing
      operations with standard cardiopulmonary bypass techniques. Group 2 consisted of
      100 patients scheduled for revascularizations using off-pump techniques. Group 3
      consisted of 100 patients who underwent operations with offpump techniques under
      controlled hemodilution (hematocrit levels kept between 25% and 28%). TTFM were
      performed with the coronary Flometer system. Mean flows, pulsatility indices, and
      flow patterns were evaluated. Twenty-five patients in each group were randomly
      assigned for control angiography 6 days postoperatively. Thromboelastographic
      (TEG) measurements were performed for each patient before and after surgery to
      evaluate the patient's coagulation status. RESULTS: The mean number of
      anastomoses was higher in group 1 than in groups 2 and 3 (P < .05). Mean arterial
      pressures and heart rates were similar between groups during measurements.
      Hematocrit values were higher in group 2 than in groups 1 and 3 (P < .05). Mean
      flows for left anterior descending coronary artery and right coronary artery
      territories were significantly lower in group 2 patients (P < .05). For the
      circumflex artery territory, mean flows did not reach statistically significant
      levels despite lower flows again in group 2. The pulsatility indices were similar
      in all 3 groups for all 3 coronary territories. Postoperative coronary
      angiographic results revealed similar graft patencies among the 3 groups (not
      significantly different). Postoperative TEG patterns failed to show a
      hypercoagulable state in off-pump patients. CONCLUSION: Off-pump CABG patients
      with hemodilution had significantly higher graft flows than off-pump CABG
      patients without hemodilution. Although we failed to show the existence of a
      hypercoagulable state for patients in the offpump group, an examination of the
      TTFM findings suggests that hemodilution may help to improve graft patency in
      offpump CABG patients during the early postoperative period.

PMID- 14721821
TI  - Early and late outcome after microwave ablation for chronic valvular atrial
      fibrillation.
AB  - BACKGROUND: Microwave energy ablation is one of the newer therapeutic options for
      surgically treating patients with chronic atrial fibrillation (AF) concomitant
      with mitral valve disease. The aim of this study was to retrospectively evaluate
      potential risk factors that may have influenced early as well as remote outcome
      in a set of patients undergoing microwave energy ablation for chronic AF.
      METHODS: Patients (n = 42) underwent ablation on an arrested heart concomitant
      with mitral valve surgery. Twelve patients also underwent tricuspid valve repair
      or replacement. Logistic regression analyses were performed to evaluate effect of
      potential risk factors on postablation rhythm status at discharge and at latest
      follow-up examination. RESULTS: With control for age, patients with recurrent AF
      at discharge (10/42 [24%]) tended to have preoperative AF of significantly longer
      duration (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.15-2.35; P =
      .01) and greater left atrial diameter (OR, 1.14; 95% CI, 1.03-1.26, P = .01) than
      patients in sinus rhythm (32/42 [76%]). At latest follow-up examination, risk of
      AF was significantly heightened with longer duration of preoperative AF (OR,
      1.47; 95% CI, 1.09-1.96; P = .01) and larger left atrium (OR, 1.12; 95% CI, 1.02
      1.23; P = .02) after adjustment for age, length of follow-up time, and presence
      of early arrhythmia recurrence. CONCLUSIONS: Results for this consecutive series
      of patients indicated that early and late success after surgical energy ablation
      may be associated with discrete patient characteristics. Longer arrhythmia
      duration and greater left atrial diameter seem to be factors independently
      influencing early and remote success, and there seems to be a self-protective
      effect of the presence of sinus rhythm at discharge. Further study would be
      valuable to confirm our findings.

PMID- 14721822
TI  - Intraoperative microwave ablation in patients undergoing valvular surgery:
      midterm results.
AB  - AIM OF THE STUDY: To assess the safety and efficacy of intraoperative microwave
      ablation to restore sinus rhythm and systolic atrial function in patients
      undergoing valvular surgery. METHODS: Forty-one patients with atrial fibrillation
      (AF) underwent operations. The mean age was 61 years (range, 45- 76 years). AF
      was permanent in 30 patients and paroxysmal in 11. Associated cardiac procedures
      were mitral valve repair in 10 patients, mitral valve replacement in 12, and
      mitro-aortic valve replacement in 19. The microwave procedure (FLEX, AFx inc.)
      was performed to create an endocardial bilateral encircling isolation of the
      ostia of the pulmonary veins. RESULTS: There was no hospital mortality or
      morbidity. The mean follow-up period was 14.2 months. At follow-up, sinus rhythm
      was found in 34 patients (82.9%). Echocardiography results at follow-up showed no
      major or minor left atrial thrombosis and only a mild impairment of the systolic
      left atrial function. CONCLUSION: Intraoperative microwave ablation is a safe and
      effective treatment to restore sinus rhythm and a mildly impaired left atrial
      function in patients with AF undergoing cardiac surgery.

PMID- 14721823
TI  - Epicardial lead implantation techniques for biventricular pacing via left lateral
      mini-thoracotomy, video-assisted thoracoscopy, and robotic approach.
AB  - PURPOSE: For optimal biventricular pacing, the left ventricular (LV) lead has
      been found to be best placed in the area where optimal concordance is achieved
      between the LV pacing site and the site of the most delayed LV wall. For
      anatomical or technical reasons, the placement of the LV lead via the coronary
      sinus at the intended target area of the LV is often not possible. An option for
      avoiding these drawbacks is the surgical implantation of the LV lead under direct
      vision. This report describes 3 epicardial lead implantation techniques that are
      less invasive. METHODS: In 80 patients with advanced heart failure and left
      bundle branch block, epicardial LV leads for biventricular pacing were implanted
      with 3 different methods: (1) left lateral mini-thoracotomy; (2) a video-assisted
      thoracoscopy approach using lead implantation tools; and (3) a robotically
      enhanced telemanipulation system. Video films are provided for all 3 techniques
      in The Heart Surgery Forum online. RESULTS: Independent of the surgical
      techniques, the intended lead location on the LV was achieved in all patients.
      Acute and 3-month LV lead thresholds were satisfactory in 79 patients (99%). Two
      lead displacements were observed. One thoracotomy was carried out after
      thoracoscopic lead placement because the patient developed an early exit block.
      Five patients who underwent an operation with the robot needed a conversion to
      thoracotomy because of technical failure of the robot (2 patients) or massive
      pleural adhesions (3 patients). There were no severe adverse events related to
      any technique. Three patients died in the hospital from the progression of end
      stage heart failure. CONCLUSION: Epicardial lead implantation for biventricular
      pacing is feasible with all 3 surgical techniques. Each method allows optimal
      lead implantation under direct vision and therefore reduces the incidence of
      nonresponders resulting from suboptimal lead placement.

PMID- 14721824
TI  - Irrigated bipolar radiofrequency ablation with transmurality feedback for the
      surgical Cox-Maze procedure.
AB  - BACKGROUND: Nonirrigated radiofrequency ablation (RFA) has been used to replicate
      the surgical scars of the Cox-Maze procedure. This study aimed to demonstrate
      that an irrigated, bipolar RFA energy source could also effectively replicate Cox
      Maze lesions with impedance monitoring to predict the transmurality of ablated
      tissue. METHODS: A complete Cox-Maze lesion pattern was created ex vivo on fresh
      porcine atria using an irrigated, bipolar RFA system. Tissues were clamped
      between opposing electrodes with steady pressure to ensure an intimate tissue
      electrode interface during ablation. A proprietary feedback and control algorithm
      monitored tissue impedance and terminated ablation when lesions were deemed
      transmural by a plateau in impedance decline. Ablation time and power, lesion
      width and length, and tissue thickness were recorded. Lesions were stained with
      1% triphenyltetrazolium chloride and sectioned for gross assessment of
      transmurality. RESULTS: One hundred thirty-seven lesions were created on 11
      porcine hearts. The total ablation time per lesion was 14.8 +/- 1.2 seconds
      (range, 10.0-19.0 seconds). Lesions averaged 4.2 +/- 1.3 mm (range, 1.3-10.2 mm)
      in width. Average tissue thickness was 3.0 +/- 1.7 mm (range, 0.5-9.9 mm).
      Crosssectional examination revealed that 100% of lesions were transmural (n =
      718), and no tissue defects were observed. CONCLUSIONS: These results indicate
      that irrigated bipolar RFA energy can produce transmural Cox-Maze lesions ex vivo
      on intact porcine atria and that impedance monitoring is a reliable predictor of
      lesion transmurality. Additional in vivo studies are under way to further
      demonstrate the efficacy and safety of irrigated, bipolar RFA technology.

PMID- 14721825
TI  - Cardiac autotransplantation for mitral valve replacement.
AB  - We present an unusual case of a 69-year-old patient with severe mitral valve
      regurgitation and extensive coronary artery disease who required mitral valve
      replacement and myocardial revascularization. With the patient on cardiopulmonary
      bypass, distal vein grafting was performed first. This procedure was followed by
      a transatrial transseptal approach to the mitral valve, but visualization of
      valve structures was extremely difficult. Following the partial excision of the
      posterior leaflet and the placement of a few pledgeted annular sutures on which
      traction was applied, access to the mitral annulus remained impossible. There
      appeared no option but to explant the heart and perform the mitral valve
      replacement ex vivo. Cardiac explantation was performed by transecting the aorta
      and pulmonary artery and completing the already extended right and left
      atriotomies. Cold blood cardioplegic solution was administered intermittently
      into the coronary sinus during the period when the heart was ex vivo. A porcine
      bioprosthesis was easily seated into the mitral annulus. Cardiac reimplantation
      consisted of repair of the previously divided atria, and end-to-end anastomoses
      of both the aorta and the pulmonary artery. While rewarming was taking place, the
      3 proximal vein graft anastomoses were performed. Temporary and permanent
      epicardial pacing leads were placed. Total ischemic time was 299 minutes, and the
      period on cardiopulmonary bypass was 359 minutes. The heart sustained good
      hemodynamics, and after full functional recovery, the patient was discharged home
      and remained well for 7 years. In view of this experience, a questionnaire was
      mailed to >3000 cardiothoracic surgeons, and responses were obtained from 1120.
      Inadequate mitral valve exposure had been experienced by 70%. To provide
      increased exposure, 50% had extended the initial atrial incision both
      horizontally and perpendicular to the atrial groove, 17% had divided the superior
      vena cava, 1% had divided the inferior vena cava, and 1% had divided both cavae.
      Furthermore, 4% of surgeons reported being forced to abandon the operation in 71
      patients because of inadequate exposure. Three hundred twenty perioperative
      deaths were directly attributed to an incomplete surgical procedure. Explantation
      of the heart, with mitral valve replacement being performed ex vivo followed by
      reimplantation, should be considered when access to the mitral valve proves
      impossible with more standard techniques.

PMID- 14721826
TI  - Experience with an albumin-glutaraldehyde tissue adhesive in sealing air leaks
      after bullectomy.
AB  - BACKGROUND: The purpose of this study was to evaluate the effectiveness of an
      albumin-glutaraldehyde tissue adhesive (BioGlue Surgical Adhesive) in preventing
      air leaks after bullectomy. METHODS: Between January 1999 and June 2002, BioGlue
      was applied over the staple or suture lines of 21 consecutive patients who
      underwent resection of bullae for persistent or recurrent pneumothorax. An age-
      and sex-matched control group of 19 bullectomy patients from our center was used
      for comparison. RESULTS: Air leak duration was significantly reduced in the
      BioGlue group (mean, 0.42 days; range, 0-2 days), compared with the control group
      (mean, 3.68 days; range, 2-11 days; P < .001). Chest tube drainage time was
      reduced to a mean of 2.33 days (range, 2-4 days) in the BioGlue group, compared
      with a mean of 5.42 days (range, 3-12 days) in the control group (P < .05).
      Morbidity and hospital stay length were slightly lower in the BioGlue group.
      There was no mortality or BioGlue-related complication in this patient cohort.
      CONCLUSIONS: The use of BioGlue as a surgical lung sealant significantly
      decreased the duration of postoperative air leaks and the time to chest tube
      removal. Use of BioGlue facilitates the postoperative course following
      bullectomy.

PMID- 14721827
TI  - A new technique for the treatment of delayed sternotomy healing: the vacuum
      therapy.
AB  - BACKGROUND: The treatment of nonhealing and infected sternotomies after cardiac
      surgery is a challenging task, with its increased rates of mortality, morbidity,
      and costs. Local vacuum therapy (V.A.C. system) allows treatment of local
      infections, thanks to continuous aspiration and the sealed dressing that
      stimulates granulation tissue formation. The purpose of this clinical
      investigation was to evaluate vacuum therapy in cardiac surgery for achieving
      healing of delayed sternotomy closure after cardiac surgery. MATERIALS AND
      METHODS: From January 1998 to December 2002, 7 patients who underwent coronary
      artery bypass surgery under cardiopulmonary bypass by median sternotomy
      approaches presented a nonhealing infected sternal surgical wound that was
      treated with local vacuum therapy. Aspiration maintained between -125 mm Hg and 
      200 mm Hg was carried out on the entire surface of the wound with a sponge
      connected hermetically to an aspiration system. The treatment was associated with
      antibiotic therapy adapted to the results of bacteriological studies of the
      aspirates. RESULTS: All patients with delayed sternotomy closure healed in
      approximately 8 weeks (2-12 weeks) with the exception of one patient who died of
      multiorgan failure after a satisfactory muscular pectoral flap. Treatment was
      possible with vacuum therapy alone (n = 2), with vacuum therapy in association by
      second intention with a skin graft (n = 1), or both with a muscular pectoral flap
      (n = 4). Sternal stability appears to be an important factor for achieving
      satisfactory and complete healing. CONCLUSIONS: This new therapy offers an
      alternative to the classic treatment of infected sternotomies in cardiac surgery,
      especially in preparing rewiring and muscular flaps for complicated cases with
      sternal instability or alone. The treatment must be instituted early to be more
      effective.

PMID- 14721988
TI  - Endoscopic multivessel coronary artery bypass grafting using automated device for
      proximal anastomosis.
AB  - BACKGROUND: The use of computer-enhanced telemanipulation robots in
      cardiothoracic surgery can reduce the need for open surgical access and enable
      closed-chest, endoscopic procedures, but these procedures hav e been limited to
      anterior target vessels. The feasibility of fully endoscopic multivessel,
      coronary artery bypass grafting (CABG) was examined. METHODS: Fully endoscopic,
      multivessel CABG solely through surgical ports was performed on 23 dogs weighing
      75 to 85 pounds. A proximal anastomosis was made with the Symmetry bypass system
      aortic connector. The aorta was cross clamped, and cardioplegia solution was
      administered through the vein graft into the ascending aorta. RESULTS: Eighteen
      of 23 procedures yielded successful proximal anastomoses and 1 to 3 distal
      anastomoses. CONCLUSION: Endoscopic anastomosis to the ascending aorta is
      feasible with the Symmetry bypass connector. Antegrade cardioplegia and aortic
      root venting can then be easily accomplished. This approach simplifies closed
      chest cardioplegic arrest for mulitivessel CABG.

PMID- 14721989
TI  - Dysfunction of left ventricle as an indication for off-pump coronary artery
      bypass grafting.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass
      carries significant risk for patients with severe left ventricular (LV)
      dysfunction. METHODS: Between 1997 and 2000, 240 patients underwent OPCAB. The
      patients were retrospectively divided into 2 groups with regard to LV function.
      Group 1 consisted of 90 patients with ejection fraction (EF) <35% and grou p 2 of
      150 patients without severe LV impairment and EF >35%. Patients were compared for
      preoperative risk factors, perioperative mortality, and postoperative
      complications. RESULTS: Preoperative expected mortality according to EuroSCORE
      was higher in group 1, 5.95, compared with group 2, 2.66 (P =.0005). A few
      preoperative risk factors were more common in group 1: urgent operation (P
      =.00001), unstable angina (P =.0018), Canadian Cardiovascular Society class (P
      =.001), myocardial infarction (P =.0001), and peripheral arteriopathy (P =.0006).
      Mean number of grafts was 1.51 in group 1 and 1.55 in group 2 with the same
      internal thoracic artery utilization. Perioperative drainage, anesthesia and
      intubation time, transfusion rate, and use of inotropes were comparable. Actual,
      nonadjusted mortality was 2.5% in group 1 and 1.4% in group 2 (P = not
      significant). Overall rates of postoperative complications were comparable; only
      use of an intraoperative balloon pump was more frequent in group 1 (P =.006).
      Postoperative stay was shorter in group 1 (P equals). CONCLUSIONS: Off-pump CABG
      for patients with LV impairment is associated with surgical outcome similar to
      that among patients with normal LV function, in spite of the presence of
      unfavorable risk factors. Off-pump surgery with selective anterior (including
      right main) arterial revascularization can be indicated in the presence of poor
      LV function.

PMID- 14721990
TI  - Randomized trial comparing off-pump to on-pump coronary artery bypass grafting in
      high-risk patients.
AB  - OBJECTIVE: The subset of patients most likely to benefit from off-pump coronary
      artery bypass grafting (CABG) remains a controversial issue, but the technique
      has been proposed to decrease postoperative mortality and morbidity. Th e
      objective of this study was to compare off-pump to onpump CABG in patients with
      known risk factors for mortality and morbidity. METHODS: Between October 2001 and
      September 2002, 65 high-risk patients were prospectively randomized to undergo
      off-pump or o n-pump CABG. Recruited patients had at least 3 of the following
      criteria: age greater than 65 years, high blood pressure, diabetes, serum
      creatinine greater than 133 mol/L, left ventricular ejection fraction lower than
      45%, chronic pulmonary diseas e, unstable angina, congestive heart failure,
      repeat CABG, anemia, and carotid atherosclerosis. Hospital mortality and
      morbidity were the primary end-points of the study. RESULTS: Six patients (9%)
      crossed over from the original randomized group. Twenty-eight patients averaging
      70 +/- 8 years of age underwent 3 +/- 1 grafts off pump, and 37 patients
      averaging 70 +/- 6 years of age underwent 3.4 +/- 1 grafts on pump.
      Revascularization was considered complete in 21 (7 5 %) of off-pump patients
      compared to 33 (89%) of onpump patients (P =.1). There were no hospital deaths in
      off-pump patients, and 2 patients (5%) undergoing onpump CABG died early
      following surgery (P =.2). Two offpump (7%) compared to 11 on-pump (30%) of
      patients presented composite end-points including death, neurological injury,
      renal failure, respiratory failure, and operative myocardial infarction after
      CABG (P =.02). CONCLUSION: The present study suggests that off-pump CABG, when
      technically feasible, significantly reduces morbidity following surgery in a
      group of high-risk patients.

PMID- 14721991
TI  - Early adaptation of the left internal thoracic artery as a blood source of y
      composite radial artery grafts in off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: Y-composite grafting with the radial artery (RA) is often used in off
      pump coronary artery bypass grafting (OPCAB). However, the early flow reserve of
      the left internal thoracic artery (LITA) as a blood source of the Y-composite RA
      graft has not been delineated. METHODS: The size of the LITA was examined
      angiographically in 42 patients who underwent OPCAB using LITA and Y-composite RA
      grafting between June 2000 and February 2002. In these patients, the LITA was
      used as a blood source of the Y-composite RA graft. The mean patient age +/- SD
      was 67 +/- 8 years. The average number of d i stal anastomoses was 3.2 +/- 0.7.
      Total coronary revascularization was carried out in 34 patients with only LITA
      and Y-composite RA grafting. RA grafting was used for revascularization of the
      circumflex artery alone in 5 patients, for the right coronary artery system (RCS)
      alone in 6 patients, and for both the circumflex and the RCS in 23 patients. The
      average number of distal anastomoses using the RA was 1.9 +/- 0.7. Flow
      measurements of the proximal LITA were achieved intraoperatively with a transit
      time flowmeter. The diameters of the LITA before and after the operation were
      measured angiographically. Intraoperative flow volume was correlated with the
      ratio of the LITA diameters before and after the operation. RESULTS: The mean
      flow rate of the LITA was 61 +/- 35 mL/min (range, 9-196 mL/min). The mean
      diameters of the LITA before and after the operation were 1.97 +/- 0.36 mm and
      2.74 +/- 0.60 mm, respectively. The mean ratio of the LITA diameter after the
      opera t ion to that before the operation was 1.43 +/- 0.27. The intraoperative
      flow volume was positively correlated with the ratio of LITA diameters (r =
      0.414; P =.006). CONCLUSION: These results demonstrate the early adaptation of
      the LITA as a blood source of the Y-composite RA graft in OPCAB and the rationale
      for using the LITA as a single blood source for total coronary artery
      revascularization.

PMID- 14721992
TI  - Interval results with right gastroepiploic bypass.
AB  - OBJECTIVE: Right gastroepiploic artery bypass grafting has proved to be a viable
      surgical choice since the mid-1980s. Long-term graft patency, however, has been
      challenged ever since. We present 43 patients who underwent right gastroepiploic
      artery bypass surgery off pump with minimal invasive techniques with an average
      follow-up period of 57.9 months since 1996. METHODS: Operative methods are
      described and were confined to a subxiphoid incision. The series consists of 43
      patients (38 male and 5 female) with an age range of 44 to 79 years. All patients
      had heart disease classified as Canadian Cardiovascular Society class III-IV and
      35/43 (81.3%) of patients had undergone 1 to 3 reoperations. Postoperatively, 93%
      had no complications. Crude mortality was 2.3%, with an expected mortality of 4%
      and risk-adjusted mortality of 1.45%. Nine patients underwent combined
      procedures. RESULTS: Of the 43 patients, 41 were alive at 57.4 months (range, 20
      76 months). Results of Doppler studies and angiography proved 95.3% and 91.6%
      patency. CONCLUSION: In this series, our highest-risk patients with reoperative
      coronary artery disease had low mortality and no intervention in this interval
      follow-up.

PMID- 14721993
TI  - Is routine use of temporary epicardial pacing wires necessary after either OPCAB
      or conventional CABG/CPB?
AB  - OBJECTIVES: Placement of temporary epicardial pacing wires (PWs) after coronary
      artery bypass graft (CABG) is routine procedure in many centers, despite
      infrequent but significant complications, including hemorrhage, tamponade, and
      death. The resurgence of off-pump CAB (OPCAB) prompted a reexamination of this
      practice. METHODS: Two hundred unselected coronary patients were prospectively
      randomized to undergo either OPCAB or conventional CABG on cardiopulmonary bypass
      (CAB G /CPB). Three patients were excluded after randomization. Management,
      including placement or avoidance of PWs, followed unbiased, criteria-driven
      protocols. Patients requiring pacing immediately prior to chest closure
      (bradycardia with cardiac ou t put < 2.2 L/min per m2, nodal or junctional
      arrhythmias, atrioventricular block) received PWs. In all other patients use of
      PWs was avoided. Duration of pacing and complications related to PW placement or
      avoidance were recorded. RESULTS: PWs were placed in 33 of 197 (17%) of patients,
      23 of whom were paced after arrival in the intensive care unit and 10 of whom
      were never paced. Twelve OPCAB versus 21 CABG/CPB patients had PWs (P =.08).
      Patients with PWs were older, more commonly female, had more chronic obstructive
      pulmonary disease, and had longer hospital stays than those not requiring PWs.
      Preoperative beta blocker use, coronary anatomy, and number of grafts performed
      were not correlated with need for PWs. No patient without PWs required
      postoperative pacing by any means nor suffered any complication attributable to
      avoidance of PWs. CONCLUSIONS: Need for pacing immediately prior to chest closure
      accurately and safely identifies coronary patients who will require postoperative
      pacing after OPCAB or CABG/ CPB. Routine use of PWs is unnecessary. OPCAB may be
      associated with a reduced requirement for PWs.

PMID- 14721994
TI  - Less invasive cardiac anesthesia: an ultra-fast-track procedure avoiding thoracic
      epidural analgesia.
AB  - BACKGROUND AND OBJECTIVE: A new "less invasive" technique avoiding thoracic
      epidural analgesia has be en tested for suitability as a routine procedure for
      cardiac anesthesia. Early postoperative extubation is an important step in this
      fasttrack procedure. MATERIALS AND METHODS: Consecutive patients (n = 547; age,
      35-82 years; mean age, 64 year s; male to female ratio, 3.5) underwent general
      anesthesia with ultra-short-acting opiates and then underwent coronary surgery (n
      = 465), valve surgery (n = 38), or combined and other procedures (n = 44) a r;.
      In 51.4% cases, coronary artery bypass grafting was performed off pump. The
      percentage of patients extubated within 10 minutes after skin closure was the
      primary end point. In addition, we attempted to identify the limiting factors of
      the procedure tested. RESULTS AND DISCUSSION: Of the 547 patients, 499 (91%) were
      extubated within 10 minutes after skin closure. Early extubation failed in 48
      (9%) of the patients. The mortality rate was 1.5%. One (0.2%) of the patients
      needed early reintubation because of pneumothorax. Postoperative myocardial
      ischemia was recorded in 10 (1.8%) of the patients. Ninetysix (17.5%) of the
      patients were treated pharmacologically for newly developed atrial fibrillation.
      None of the patients needed hemodialysis. Transient neurological disorders were
      recorded in 10 (1.8%) of the patients. The early extubation failure group showed
      statistically significantly higher rates of preoperative lung dysfunction, use of
      extracorporeal circulation, administration of inotropic drugs in the operating
      room, and statistically significantly longer duration of surgery. CONCLUSION:
      Early extubation proved suitable as a routine procedure for the vast majority of
      patients. With a good postoperative analgetic protocol, there is no need for
      thoracic epidural analgesia. Such avoidance of thoracic epidural analgesia is a
      further step in minimizing invasiveness in cardiac surgery.

PMID- 14721995
TI  - The world wide web and robotic heart surgery.
AB  - PURPOSE: The primary goal of this study was to (1) determine patients' access to
      and use of the Internet for healthrelated information before and after endoscopic
      atraumatic coronary artery bypass (Endo-ACAB) surgery, (2) investigate patients'
      methods of searching for such information, and (3) suggest future improvements
      for Internet-based patient education. The secondary goal of this study was to
      determine (1) patients' health-related quality of life and (2) degree of
      satisfaction following the Endo-ACAB procedure. METHODS: A follow-up study was
      conducted of 50 consecutive patients who had undergone Endo-ACAB procedures at
      the Center for Less Invasive Cardiac Surgery and Robotic Heart Surgery in
      Buffalo, New York. Study surveys were designed cooperatively by a communication
      scientist specializing in Internet studies and cardiac surgeons. Patients
      completed surveys over a period of 18 months, from January 2001 to June 2002.
      RESULTS: All 50 patients (100%) in the targeted study group completed the survey.
      Forty-four (88%) of these respondents reported having Internet access. The Web
      was cited as the most popular source of initial information on Endo-ACAB, with
      36% of patients (18) first learning about the procedure through an Internet
      search. All 44 patients with Internet access used the Web as an additional source
      of information before surgery, but only 20% (7/35) did so after surgery. Most
      patients (91%, 40/44) felt that their surgeon should develop a Web site to detail
      the Endo-ACAB procedure. An investigation of patient quality of life showed that
      96% of patients were not experiencing any symptoms related to t heir surgery. All
      50 patients reported high degrees of satisfaction with the Endo-ACAB procedure,
      and 98% (49) said that they would recommend the surgery to someone else.
      CONCLUSION: A vast majority of patients are realizing the benefits of the
      Internet as a tool to educate themselves, both before and after surgery. The
      request by an overwhelming majority of patients that surgeons develop Web sites,
      however, shows that patients may not be completely satisfied with the current
      form or content of health sites on the Internet. Surgeons will see the benefits
      of Web-based education only when they ensure that their patients have access to
      adequate and credible health-related information. The early results of robotic
      surgery suggest a promising future and the need to investigate the role of the
      Internet in its growth.

PMID- 14721996
TI  - Intraluminal coronary shunting preserves regional myocardial perfusion and
      function.
AB  - BACKGROUND: Coronary artery hemostasis during offpump coronary artery bypass
      (OPCAB) may be achieved with extraluminal coronary occlusion or intraluminal
      coronary shunting. We sought to determine with a normal porcine beating-heart
      model whether coronary shunting preserves regional myocardial perfusion and
      function compared with coronary occlusion. METHODS: Six pigs (50-60 kg) underwent
      sternotomy and instrumentation. Two pairs of ultrasonic crystals were placed in
      the distribution of t h e left anterior descending (LAD) and left circumflex
      (LCx) arteries for measurement of fractional change in area (FCA), an index of
      regional contractility. Regional myocardial blood flow (RMBF) was determined with
      radiolabeled microspheres. Data were recorded for each animal at baseline and
      after LAD arteriotomy and vascular control with (1) a 1.5-mm intraluminal shunt,
      (2) proximal occlusion, and (3) proximal and distal occlusion. RESULTS: One pig
      experienced ventricular fibrillation during LAD manipulation and was excluded
      from the study. Data were summarized for the remaining 5 animals. Coronary
      shunting maintained RMBF and function (FCA) compared with baseline. Proximal
      occlusion led to 50% (P =.05) and 47% (P =.04) decreases in RMBF and FCA,
      respectively, in the LAD region. Proximal and distal occlusion led to 55% (P
      =.03) and 51% (P = 02) decreases in RMBF and FCA, respectively, in the LAD
      region. There were no significant changes in RMBF or FCA in the LCx (control)
      region. CONCLUSION: Intraluminal coronary shunting is capable of preserving
      distal myocardial perfusion and function in a normal porcine heart. Coronary
      occlusion, in contrast, significantly reduces regional perfusion and function.
      More frequent use of intracoronary shunting may facilitate OPCAB by minimizing
      ischemia and hemodynamic compromise.

PMID- 14721997
TI  - Biventricular pacing during cardiac operations.
AB  - BACKGROUND: Biventricular pacing (resynchronization therapy) improves the
      duration and quality of life in a subset of patients with congestive heart
      failure, but this technique has received little attention in the cardiac surgery
      literature. This report presents some preliminary ideas about its rationale and
      technique, and some likely indications for this procedure during the performance
      of cardiac operations. METHODS: We briefly summarize the theory and the results
      of the randomized clinical trials of resynchronization therapy that led us to
      consider biventricular pacing for high-risk cardiac surgery patients. We present
      s ome techniques for using temporary and permanent biventricular pacing in the
      operating room. We review the hospital records and present early results of the
      first 25 patients in whom we implanted permanent left ventricular free wall
      pacing electrodes with the intent of implanting biventricular pacing devices.
      CONCLUSIONS: Biventricular pacing has great potential to simplify the management
      and improve the outcomes of some cardiac surgical patients.

PMID- 14721998
TI  - Minimally invasive direct coronary artery bypass: current experience.
AB  - BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) via a small
      incision has been performed for revascularization of the left anterior descending
      artery with the left internal mammary artery. In this study, we analyzed outcome
      in patients who underwent MIDCAB. METHODS: Between June 1997 and July 2002, a
      total of 125 patients (96 men and 29 women; mean age, 65.1 +/- 9.6 years)
      underwent MIDCAB. Perioperative and follow-up data were entered into a structured
      database. RESULTS: Coronary anastomosis time was 17.0 +/- 5.0 minutes. Mean
      intubation period, intensive care unit stay, and postoperative hospital stay were
      4.0 +/- 2.8 hours, 1.3 +/- 0.8 days, and 9. 7 +/- 4.6 days, respectively. There
      were no hospital deaths or cases of postoperative heart failure, myocardial
      infarction, renal failure, prolonged ventilation (>2 days), or stroke. During the
      follow-up period of 3.3 +/- 1.5 years, 12 patients developed angina, and there
      were 10 deaths. The actuarial 3-year survival rate was 92.6%, and the event-free
      rate was 87.1%. CONCLUSION: MIDCAB can be performed with early recovery with
      minimum mortality and morbidity. The longterm results after MIDCAB are
      acceptable.

PMID- 14721999
TI  - Emergent endovascular interventions for contained rupture of thoracic aortic
      aneurysms.
AB  - BACKGROUND: The purpose of our study was to assess in an emergency setting the
      feasibility of endovascular stent graft treatment of contained ruptures of
      thoracic aortic aneurysms. METHODS: Seven patients with contained ruptures of
      thoracic aortic aneurysms from a series of 54 endovascular interventions were
      treated by the deployment of an aortic stent graft. In all cases, hemothorax was
      present. Acute deployment was performed with the patient under general
      anesthesia, and access was gained via the common femoral or iliac arteries. After
      a follow-up o f 12 months, the patients were evaluated by computed tomography.
      RESULTS: One patient died perioperatively. The procedure was technically
      successful in 5 patients. Perioperatively and at follow-up, there were no cases
      of paraplegia, stent graft migration, or endoleaks. There were, however, 2 cases
      of access failure, 1 case of temporary renal failure, and 2 patients who required
      prolonged mechanical ventilation. CONCLUSION: The acute treatment of contained
      ruptures of thoracic aortic aneurysms is feasible. This form of treatment seems
      to be a promising option in the treatment of these high-risk patients.

PMID- 14722000
TI  - Damage to coronary arteries during mitral valve surgery.
AB  - BACKGROUND: The rheumatic cardiac valve diseases are one of the most important
      heart problems in Turkey. In mitral valve surgery, the relationship between the
      anulus fibrosus sinister and the coronary arteries is extremely critical for the
      postoperative life of the patient. METHODS: The study was performed with human
      adult hearts. The aim of this study of 50 hearts was to understand the existing
      correlations between the mitral annulus and the coronary arteries. We determined
      the right or left dominance or codominance of the anulus fibrosus sinister on
      each heart and stu died the relationship of the mitral annulus to the circumflex
      coronary artery (CCA) and the left posterior descending coronary artery. RESULTS:
      The distances of the anulus fibrosus sinister from the CCA and interventricularis
      posterior arteries w e re measured with a flexible ruler. In 19 of 50 cases, the
      distance of the coronary artery from the annulus was 3 mm at 23 different points,
      2 mm at 8 different points, and 1 mm at 2 different points. CONCLUSIONS: In
      mitral valve surgery, damage to the CCA can occur, especially in patients with
      left coronary dominance or codominance in which the CCA is running in the
      atrioventricular groove very close to the mitral annulus. Therefore, this study
      emphasizes the importance of knowing the coronary artery anatomy preoperatively.

PMID- 14722001
TI  - Influence of endoscopic versus traditional saphenectomy on event-free survival:
      five-year follow-up of a prospective randomized trial.
AB  - BACKGROUND: Endoscopic harvesting of the greater saphenous vein is increasingly
      used during cardiac surgery to improve patient satisfaction and reduce the wound
      complications associated with traditional open techniques. Although histologic
      studies suggest no significant difference in vein quality between these two
      techniques, long-term follow-up is lacking to address whether graft patency and
      event-free survival are influenced by the harvest method. METHODS: A total of 112
      isolated coronary artery bypass patients were prospectively randomized to have
      veins harvested using either an endoscopic (n = 54) or traditional (n = 58)
      technique. Groups were demographically similar with regard to preoperative risk
      stratification and coronary procedures performed. Event-free survival (freedom
      from death, myocardial infarction, or recurrent angina) and use of outpatient
      resources for resolution of wound complications were determined. Follow-up was
      100% at 5 years. RESULTS: Five-year actual event-free survival was similar in
      patients with endoscopic versus traditionally harvested v e ins (75% versus 74%,
      P =.85). The number of outpatient office visits required to manage each wound
      complication to complete resolution was significantly less following endoscopic
      versus traditional vein harvest (1.5 versus 6 visits, P =.001). CONCLUSIONS:
      Wound complication management following endoscopic versus traditional vein
      harvest requires less resource utilization. Five-year follow-up of a prospective
      randomized trial demonstrates that use of endosco pic versus traditionally
      harvested saphenous veins does not influence event-free survival.

PMID- 14722002
TI  - Segmentation of the left internal thoracic artery: a new technique for maximal
      arterial grafting.
AB  - The left internal thoracic artery lpa r;LITA) is the preferred graft with the
      best patency rate in coronary artery bypass grafting (CABG). To maximize its use,
      we developed a technique of grafting 2 distant coronary arteries with the LITA,
      using its distal portion segmented to construct a Y graft with either the in situ
      LITA or right internal thoracic artery (RITA). We applied this technique in 51
      patients. The distal segment of the LITA was used to create a Y graft in 4
      different configurations according to coronary pathology. Offpump grafting was
      performed in 11% of cases. The use of a distal segment of the LITA was thus
      extended not only to the left anterior descending artery and branches but also to
      the circumflex and right coronary artery territories.

PMID- 14722003
TI  - Endoscopic computer-enhanced mediastinal mass resection using robotic technology.
AB  - BACKGROUND: Robotic technology can be used to facilitate the performance of a
      variety of cardiac surgical procedures, including internal mammary artery
      mobilization, atrial septal defect repair, mitral valve repair, and coronary
      artery bypass grafting. This report describes t h e use of robotic technology for
      resection of mediastinal masses. METHODS: Two patients underwent mediastinal mass
      resection performed using the Da Vinci robotic surgical system (Intuitive
      Surgical, Mountain View, CA, USA). The first patient had a 3 x 4-cm mass located
      in the left superiorposterior mediastinum, abutting the left subclavian artery.
      The second patient had a 2.7 x 1.9-cm mass located in the left chest wall.
      RESULTS: Both mediastinal masses were successfully excised using a totally
      endoscopic robotic approach with three 1-cm incisions. Neither case was converted
      to a thoracotomy or sternotomy. There were no postoperative complications. Both
      patients were discharged on postoperative day 2. CONCLUSIONS: Resection of a
      mediastinal mass ca n be performed safely and effectively using robotic
      technology. By minimizing surgical trauma, this approach is likely to yield a
      hastened postoperative recovery and improved quality of life.

PMID- 14722004
TI  - Thoracoscopic lobectomy using robotic technology.
AB  - BACKGROUND: While robotic technology is gaining popularity in cardiac surgery, it
      also is being used to facilitate thoracoscopic procedures, such as insertion of
      phrenic pacemakers and resection of mediastinal masses. This report describes the
      use of robotic technology in performing thoracoscopic lobectomy. METHODS: One
      patient underwent a left lower lobectomy with the da Vinci robotic surgical
      system (Intuitive Surgical, Mountain View, CA, USA). With 3 1-cm port incisions
      and a 4-cm minithoracotomy in the left chest, visualization of the pertinent
      anatomy was excellent. Standard lymph node dissection was performed. The specimen
      was removed through the 4-cm minithoracotomy incision. RESULTS: Pathologic
      examination revealed mucinous adenocarcinoma. The margins of the specimen were
      negative, and there was no vascular or bronchial invasion. The patient's
      postoperative course was uneventful, and he was discharged to home on
      postoperative day 5. CONCLUSION: Robotic technology enhances visualization and
      instrument dexterity during thoracoscopic intrathoracic procedures. This
      technology can be used to facilitate development of minimally invasive thoracic
      approaches.

PMID- 14722005
TI  - Ultrafast computed tomography for quality control of automated proximal
      anastomoses.
AB  - BACKGROUND: The Symmetry aortic connector uses a nitinol implant to create
      proximal anastomoses with saphenous vein grafts. Multiple detector-row cardiac
      computed tomography (MDCT) is used as a noninvasive method of quality control at
      our institution. METHODS: In 50 elective coronary artery bypass grafting patients
      who participated in a randomized trial comparing automated with conventionally
      hand-sewn proximal anastomoses, MDC T was performed on postoperative day 5. Fifty
      three automated Symmetry anastomoses were created in 34 patients (group 1).
      Twenty-five conventionally hand-sewn anastomoses created in 16 patients served as
      controls (group 2). Graft patency and the presence or absence of high-grade
      stenosis at the proximal anastomotic site were evaluated. RESULTS: In group 1, 2
      (3.8%) of the grafts were found occluded at MDCT or coronary angiography, and no
      further relevant stenosis was observed. In group 2, at postoperative MDCT all
      grafts were found patent without significant narrowing of the proximal
      anastomotic site. CONCLUSIONS: The feasibility of proximal anastomoses using the
      Symmetry device has been reported. Patency control with invasive angiography has
      been performed by other groups. With MDCT, noninvasive evaluation of proximal
      anastomotic quality and graft patency is possible, even if nitinol is implanted.

PMID- 14722006
TI  - Off-pump coronary bypass grafting is associated with less myocardial injury than
      coronary bypass surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Excessive myocardial necrosis following coronary artery bypass
      grafting is associated with adverse outcome. The present study was designed to
      assess the extent of myocardial injury after conventional coronary artery bypass
      grafting with cardio pulmonary bypass (ONCAB) compared with off-pump coronary
      artery bypass (OPCAB). METHODS: Measurements of serum cardiac troponin T (TnT)
      were obtained in 137 consecutive, unselected patients who underwent coronary
      artery bypass grafting. Serial blood sampling was performed at 3 time intervals
      after surgery: immediately postoperatively, 6 to 12 hours postoperatively, and 18
      to 24 hours postoperatively. RESULTS: ONCAB patients totaled 122, and OPCAB
      patients numbered 15. Ten patients in the ONCAB group suffered perioperative
      complications, compared with no patients in the OPCAB group. At each time point
      examined, OPCAB patients exhibited significantly less release of TnT than ONCAB
      patients (immediately postoperative TnT, 1.99 +/- 4.75 ng/mL versus 0.20 +/- 0.32
      ng/mL, P =.004; 6- to 12-hour TnT, 2.28 +/- 3.66 ng/mL versus 0.37 +/- 0.32
      ng/mL, P =.001; and 18- to 24-hour TnT 1.59 +/- 3.49 ng/mL versus 0.30 +/- 0.32
      ng/mL, P =.01). When ONCAB patients with perioperative ischemic complications
      were excluded, the differences between the 2 groups remained. The OPCAB patients
      still demonstrated less TnT release, typically 5- to 6-fold less than for ONCAB
      patients. CONCLUSIONS: The nearly 6-fold reduction of postoperative TnT
      associated with OPCAB suggests that off-pump surgery may offer superior
      cardioprotection than coronary artery bypass grafting with conventional
      cardiopulmonary bypass. ?par

PMID- 14722007
TI  - Improving hemodynamics by atrial pacing during off-pump bypass surgery.
AB  - BACKGROUND: To avoid hemodynamic deterioration during tilting of the heart in off
      pump surgery, we perform atrial pacing. We describe hemodynamic evaluation of
      this simple maneuver. METHODS: Eleven consecutive patients (8 men, 3 women; age,
      68.14 +/- 10.3 years; left ventricular ejection fraction, 51.17% +/- 18.6%)
      admitted for coronary artery bypass grafting were equipped with a PiCCO catheter
      (Pulsion Medical Systems, Munich, Germany) for monitoring of cardiac output (CO),
      cardiac index (CI), stroke volume (SV), heart rate (HR), and systemic vascular
      resistance. In addition, mean and systolic arterial pressure (RRm, RRs) as well
      as left atrial pressure (LAP) were monitored. During the procedure, temporary
      pacemaker wires were installed, and hemodynamic monitoring was performed before
      and after atrial pacing. All procedures were performed with the same standardized
      offpump technique. RESULTS: All patients survived the procedure without inotropic
      support. In all cases a branch of the circumflex artery was grafted. The number
      of grafts per patient was 2.7. There was a statistically significant increase in
      RRs (11.12 mm Hg), RRm (9.72 mm Hg), HR (31.6 beats/min), CO (1.09 L/min), and CI
      (0.61 L/min per m2) (P <.005). SV decreased statistically significantly (11.8 mL,
      P <.005) as did LAP (6 mm Hg, P < .05). CONCLUSIONS: Atrial pacing increases
      intraoperative RRs, RRm, CO, and CI and decreases SV and LAP significantly, thus
      offering stable hemodynamics during off-pump surgery. In the last 400 consecutive
      off-pump coronary artery bypass grafting procedures, there was only 1 (0.25%)
      conversion to cardiopulmonary bypass.

PMID- 14722008
TI  - Totally endoscopic multivessel coronary artery bypass surgery using the da Vinci
      surgical system: a feasibility study on cadaveric models.
AB  - BACKGROUND: The aim of the study was to develop a totally endoscopic coronary
      artery bypass procedure for the treatment of multivessel disease (MVTECAB).
      METHODS: Procedure development was conducted on 6 human cadavers with the da
      Vinci Surgical System. For aortic clamping, a transthoracic aortic clamp was
      applied. The proximal anastomoses of vein grafts were created transthoracically
      with the Corlink automated anastomosis device. The target vessels on the heart
      were exposed with a modified endoscopically applicable Starfish vacuum device. In
      1 cadaver, the endo-sling and endoscopic fan retractors were studied for exposure
      support. RESULTS: Harvesting of bilateral internal thoracic arteries was easily
      accomplished. Aortic clamping was easier from the right side. In the left-side
      approach, the proximal anastomoses were completed without leakage in all 3
      cadavers. One incorrect deployment occurred, and the deployment needed to be
      redone. In the right-si d e approach, 1 proximal anastomosis was performed
      without leakage, and another needed to be repaired for incorrect deployment. The
      fan retractors either covered too much of the targeted area of the heart surface
      or did not provide good manipulation capabilities. The endo-sling enabled
      atraumatic exposure of the target vessels. The modified Starfish performed
      sufficiently for exposing target vessels. Problems were found with epicardial fat
      clogging the Starfish suction chamber and with bending of the suction tube neck,
      both of which resulted in a loss of tissue contact. Two of the cadavers
      approached from the left side were completely revascularized with 3 grafts, and 4
      anastomoses were performed on the third cadaver. Triple-vessel revascularization
      was performed in the cadavers approached from the right side. CONCLUSION: This
      study demonstrates the feasibility of performing an MVTECAB on the arrested heart
      with the da Vinci Surgical System. Further procedure development is necessary to
      optimize the synergistic effects of the technologies used and to introduce this
      operation into clinical practice.

PMID- 14722010
TI  - Radial artery harvest using endoscopic techniques.
AB  - BACKGROUND: Endoscopic vessel harvest for coronary artery bypass conduit has
      become a routine procedure. With the advancement of endoscopic equipment, radial
      arteries can be safely harvested with excellent cosmetic results. METHODS: One
      hundred consecutive patients undergoing coronary artery bypass grafting underwent
      endoscopic radial artery harvest without complications requiring intervention.
      The vessel was accessed through a 3-cm long, longitudinal incision performed
      several millimeters medial to the palpated artery to avoid the lateral
      antebrachial cutaneous nerve. Commercially available endoscopic retractors, using
      ultrasonic or direct-current shears, were used to ligate side branches and
      mobilize the pedicled artery and satellite veins. Ligation was performed with
      clips at the wrist, endo-loops proximally, and endoshears for transection.
      RESULTS: Patient age ranged from 42 to 88 years; 70% of the patients were men,
      and 26% were diabetic. Le f t radial arteries were preferentially harvested. All
      arteries were used and no further conduit was needed because of inadequate
      length. In 2 patients subcutaneous hematomas formed postoperatively and resolved
      without exploration. Although some thenar dysthesia was present in 14 patients,
      no permanent neurovascular injuries occurred. There were no infections, although
      skin edges did get traumatized from the retractor. COMMENT: Radial arteries can
      be harvested in a reproducible, safe, and efficient manner wi th less morbidity
      and better patient satisfaction.

PMID- 14722009
TI  - A novel custom-made long shunt simplifies the performance and improves the
      results of beating-heart surgery.
AB  - BACKGROUND: The occurrence of a snare-related stenosis after beating-heart
      surgery prompted the search for an alternative method of hemostasis. Because of
      the shortcomings of commercial coronary shunts a novel custom-made coronary
      shunting technique was devised. It involves the use of varying lengths of 1.2-mm
      Silastic tubing secured with a fine silk "tag" suture. The technique of
      construction and deployment of the shunts is presented. A retrospective
      comparison of 500 off-pump coronary artery bypass graft (OPCAB) cases done with
      snares was made with 300 cases using custom-made long shunts (CLS). METHOD:
      Between June 1998 and December 2 000, 500 OPCAB surgeries were done using the
      Platypus stabilizer and Silastic snares for hemostasis. Thereafter, 300 surgeries
      were done with the same stabilizer but using CLS instead of snares. RESULTS: The
      CLS group had a perioperative infarction incidence of 1.6% compared with 4.4% in
      the snare group. Other measured parameters remained unchanged, but there was a
      profound, but subjectively noted, reduction in the incidence of hemodynamic
      instability in the shunted cases. CONCLUSION: The best method for control of
      coronary bleeding during beating-heart surgery remains controversial. There is
      increasing evidence that snares can cause artery damage and spasm. Shunting
      avoids this problem while enhancing hemodynamic stability and facilitating
      accurate anastomoses. The case against shunts is based mainly on inconvenience
      but this problem has been substantially negated by the introduction of the CLS
      technique.

PMID- 14722011
TI  - Endoscopic aortic valve replacement.
AB  - During the last 8 years, many different approaches for minimally invasive aortic
      valve surgery have emerged. We have developed a technique that enables total
      endoscopic aortic valve replacement with port access, via a small right lateral
      thoracotomy with only soft tissue retraction and minimally invasive aortic
      crossclamping. The operation is performed under video guidance, since no direct
      eye vision is possible. We believe this is the first such operation performed in
      cardiac surgery and that it mak es possible broadening of indications for
      nonsternotomy-video-directed surgery in the future.

PMID- 14722012
TI  - Early release of neonatal ureteral obstruction preserves renal function.
AB  - The incidence of congenital hydronephrosis is approximately 1% and is often
      associated with renal insufficiency. It is unknown whether early release is
      essential to prevent deterioration of renal function. Rats were subjected to
      partial unilateral ureteral obstruction (PUUO) on postnatal day 2. The
      obstruction was left in place or released after 1 or 4 wk. Renal blood flow (RBF)
      and kidney size were measured sequentially over 24 wk using MRI. In rats in which
      the obstruction was left in place, RBF of the obstructed kidney was progressively
      reduced to 0.92 +/- 0.17 vs. 1.79 +/- 0.12 ml.min(-1).100 g body wt(-1) (P <
      0.05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney
      was severely reduced at 24 wk: 172 +/- 36 vs. 306 +/- 42 microl.min(-1).100 g
      body wt(-1) (P < 0.05). These changes were preceded by development of severe
      hydronephrosis and obstructive nephropathy with a reduction in total protein
      content: 45 +/- 3 vs. 58 +/- 4 mg/kidney. Moreover, nonreleased PUUO caused a
      marked natriuresis (0.32 +/- 0.07 vs. 0.11 +/- 0.02 micromol.min(-1).100 g body
      wt(-1), P < 0.05) and impaired solute free water reabsorption (0.47 +/- 0.16 vs.
      2.71 +/- 0.67 microl.min(-1).100 g body wt(-1), P < 0.05), consistent with a
      significant downregulation of Na-K-ATPase to 62 +/- 7%, aquaporin-1 to 53 +/- 3%,
      and aquaporin-3 to 53 +/- 7% of sham levels. Release after 1 wk completely
      prevented development of hydronephrosis, reduction in RBF and glomerular
      filtration rate, and downregulation of renal transport proteins, whereas release
      after 4 wk had no effect. These results suggest that early release of neonatal
      obstruction provides dramatically better protection of renal function than
      release of obstruction after the maturation process is completed.

PMID- 14722014
TI  - Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and
      exacerbates renal fibrosis after unilateral ureteral obstruction.
AB  - Tissue homeostasis is determined by the balance between oxidants and
      antioxidants. Catalase is an important antioxidant enzyme regulating the level of
      intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase
      deficiency on renal tubulointerstitial injury induced by unilateral ureteral
      obstruction (UUO) has been studied in homozygous acatalasemic mutant mice
      (C3H/AnLCs(b)Cs(b)) compared with wild-type mice (C3H/AnLCs(a)Cs(a)). Complete
      UUO caused interstitial cell infiltration, tubular dilation and atrophy, and
      interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys
      (OBK) of both mouse groups. However, the degree of injury showed a significant
      increase in OBK of acatalasemic mice compared with that of wild-type mice until
      day 7. The deposition of lipid peroxidation products including 4-hydroxy-2
      hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules
      of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly
      increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of
      mitochondrial pathway-derived apoptosis, increased in dilated tubules of
      acatalasemic mice. The level of catalase activity remained low in acatalasemic
      OBK until day 7 without compensatory upregulation of glutathione peroxidase
      activity. The data indicate that acatalasemia exacerbated oxidation of renal
      tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This
      study demonstrates that catalase deficiency enhanced tubulointerstitial injury
      and fibrosis in a murine model of UUO and thus supports the protective role of
      catalase in this model.

PMID- 14722017
TI  - High glucose concentration stimulates intracellular renin activity and
      angiotensin II generation in rat mesangial cells.
AB  - Increased intrarenal renin-angiotensin system activity contributes to diabetic
      nephropathy. ANG II generation in mesangial cells (MC) is increased by high
      glucose (HG) exposure. This study assessed the mechanisms involved in the glucose
      induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted
      prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase
      in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels
      for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly
      elevated. However, after shorter periods of 24 h of HG stimulation the mRNA
      levels of the enzymes prorenin and cathepsin B, besides that for ACE, were
      significantly increased. The results suggest that the HG-induced increase in ANG
      II generation in MC results from an increase in intracellular renin activity
      mediated by at least three factors: a time-dependent stimulation of (pro)renin
      gene transcription, a reduction in prorenin enzyme secretion, and an increased
      rate of conversion of prorenin to active renin, probably mediated by cathepsin B.
      The increase in angiotensinogen mRNA in parallel to increased renin activity
      indicates that HG also increased the availability of the renin substrate. The
      consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly
      involved in the increased mesangial ANG II generation induced by HG.

PMID- 14722018
TI  - Expression of claudin-7 and -8 along the mouse nephron.
AB  - Claudins are integral membrane proteins of the tight junction that determine the
      magnitude and selectivity of paracellular permeability in epithelial tissues. The
      mammalian renal tubule exhibits considerable heterogeneity in the permeability
      properties of its different segments. To determine the nephron segment
      localization of claudin-7 and -8, immunofluorescence staining of mouse kidney
      sections was performed using isoform-specific antibodies. Claudin-8 was found to
      be expressed primarily at the tight junction along the entire aldosterone
      sensitive distal nephron and in the late segments of the thin descending limbs of
      long-looped nephrons. This pattern of expression is consistent with the putative
      role of claudin-8 as a paracellular cation barrier. By contrast, claudin-7 was
      found in the same nephron segments as claudin-8, but it was expressed primarily
      at the basolateral membrane.

PMID- 14722019
TI  - Comparison of acute and chronic antioxidant interventions in experimental
      renovascular disease.
AB  - Reactive oxygen species (ROS) can modulate renal hemodynamics and function both
      directly, by leading to vasoconstriction, and indirectly, by inducing renal
      inflammation and tissue growth. The involvement of oxidative stress in the
      pathogenesis of renovascular disease (RVD) is increasingly recognized, but the
      relative contribution of long-term tissue injury to renal dysfunction remains
      unclear. We hypothesized that functional and structural alterations elicited by
      oxidative stress in RVD would be more effectively modulated by chronic than by
      acute antioxidant intervention. Renal hemodynamics and function were quantified
      in vivo in pigs using electron-beam computed tomography at baseline and after
      vasoactive challenge (ACh and sodium nitroprusside); after 12 wk of RVD
      (simulated by concurrent hypercholesterolemia and renal artery stenosis, n = 7);
      RVD acutely infused with the SOD-mimetic tempol (RVD+tempol, n = 7); RVD
      chronically supplemented with antioxidant vitamins C (1 g) and E (100 IU/kg;
      RVD+vitamins, n = 7); or control (normal, n = 7). Renal tissue was studied ex
      vivo using immunoblotting and immunohistochemistry. Basal renal blood flow (RBF)
      and glomerular filtration rate were similarly decreased in all RVD groups. ACh
      stimulated RBF remained unchanged in RVD, increased in RVD+tempol, but further
      increased (similarly to normal) in RVD+vitamins (P < 0.05 vs. RVD). Furthermore,
      RVD+vitamins also showed a decreased presence of superoxide anion, decreased
      NAD(P)H-oxidase and nitrotyrosine expression, increased endothelial nitric oxide
      synthase expression, and attenuated renal fibrosis. Chronic antioxidant
      intervention in early RVD improved renal hemodynamic responses more effectively
      than acute intervention, likely due to increased nitric oxide bioavailability and
      decreased structural injury. These suggest that chronic tissue changes play an
      important role in renal compromise mediated by oxidative stress in RVD.

PMID- 14722022
TI  - Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery
      of function after ischemia in the isolated perfused heart.
AB  - The aim of this study was to determine whether the transition from insulin
      resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic
      changes in the myocardium that increase the sensitivity to ischemic injury.
      Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty
      (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia
      (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but
      not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became
      progressively worse by 24 wk. In spontaneously beating hearts rate-pressure
      product (RPP) was depressed in the ZDF groups compared with age-matched Controls,
      primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF
      groups; however, this was accompanied by a significant decrease in left
      ventricular developed pressure. There was also greater contracture during LFI in
      the ZDF groups compared with the Control group; surprisingly, however, functional
      recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk
      ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This
      improvement in recovery in the ZDF diabetic groups was independent of substrate
      availability, severity of ischemia, and duration of diabetes. These data
      demonstrate that, although the development of type 2 diabetes leads to
      progressive contractile and metabolic abnormalities during normoxia and LFI, it
      was not associated with increased susceptibility to ischemic injury.

PMID- 14722023
TI  - Insulin-like growth factor I receptors are more abundant than insulin receptors
      in human micro- and macrovascular endothelial cells.
AB  - Micro- and macroangiopathy are major causes of morbidity and mortality in
      patients with diabetes. Our aim was to characterize IGF-I receptor (IGF-IR) and
      insulin receptor (IR) in human micro- and macrovascular endothelial cells.
      Cultured human dermal microvascular endothelial cells (HMVEC) and human aortic
      endothelial cells (HAEC) were used. Gene expression was measured by quantitative
      real-time RT-PCR and receptor protein by ligand-binding assay. Phosphorylation of
      IGF-IR beta-subunit was analyzed by immunoprecipitation and Western blot. Glucose
      metabolism and DNA synthesis was assessed using [(3)H]glucose and [(3)H]thymidine
      incorporation, respectively. We detected gene expression of IGF-IR and IR in HAEC
      and HMVEC. IGF-IR gene expression was severalfold higher than that of IR. The
      specific binding of (125)I-IGF-I was higher than that of (125)I-insulin in HAEC
      and HMVEC. Insulin and the new, long-acting insulin analog glargine interacted
      with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself.
      Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M)
      and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M).
      IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)
      10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and
      insulin had no significant effects at 10(-9)-10(-7) M. Human micro- and
      macrovascular endothelial cells express more IGF-IR than IR. IGF-I and high
      concentrations of glargine and insulin activates the IGF-IR. Glargine has a
      higher affinity than insulin for the IGF-IR but probably has no effect on DNA
      synthesis at concentrations reached in vivo.

PMID- 14722024
TI  - Coordinated increase in albumin, fibrinogen, and muscle protein synthesis during
      hemodialysis: role of cytokines.
AB  - Serum albumin, fibrinogen levels, and lean body mass are important predictors of
      outcome in end-stage renal disease (ESRD). We estimated the fractional synthesis
      rates of albumin (FSR-A), fibrinogen (FSR-F), and muscle protein (FSR-M) in nine
      ESRD patients and eight controls, using primed constant infusion of l-[ring
      (13)C(6)]phenylalanine. Cytokine profile and arteriovenous balance of amino acids
      were also measured. ESRD patients were studied before (Pre-HD) and during
      hemodialysis (HD). Plasma IL-6, IL-10, and C-reactive protein increased
      significantly during HD. Despite a decrease in the delivery of amino acids to the
      leg, the outflow of the amino acids increased during HD. The net balance of amino
      acids became more negative during HD, indicating release from the muscle. HD
      increased leg muscle protein synthesis (45%) and catabolism (108%) but decreased
      whole body proteolysis (15%). FSR-A during HD (9.7 +/- 0.9%/day) was higher than
      pre-HD (6.5 +/- 0.9%/day) and controls (5.8 +/- 0.5%/day, P < 0.01). FSR-F
      increased during HD (19.7 +/- 2.6%/day vs. 11.8 +/- 0.6%/day, P < 0.01), but it
      was not significantly different from that of controls (14.4 +/- 1.4%/day). FSR-M
      intradialysis (1.77 +/- 0.19%/day) was higher than pre-HD (1.21 +/- 0.25%/day)
      and controls (1.30 +/- 0.32%/day, P < 0.001). Pre-HD FSR-A, FSR-F, and FSR-M
      values were comparable to those of controls. There was a significant and positive
      correlation between plasma IL-6 and the FSRs. Thus, in ESRD patients without
      metabolic acidosis, the fractional synthesis rates of albumin, fibrinogen, and
      muscle protein are not decreased pre-HD. However, HD increases the synthesis of
      albumin, fibrinogen, and muscle protein. The coordinated increase in the FSRs is
      facilitated by constant delivery of amino acids derived from the muscle
      catabolism and intradialytic increase in IL-6.

PMID- 14722025
TI  - Pancreatic beta-cells communicate via intermittent release of ATP.
AB  - The role of external ATP for intercellular communication was studied in glucose
      stimulated pancreatic beta-cells isolated from ob/ob mice. Digital image analyses
      with fura-2 revealed spontaneous transients of cytoplasmic Ca2+ appearing in
      synchrony in the absence of cell contacts. After removal of slow oscillations
      with methoxyverapamil, addition of ATP (0.1-100 microM) resulted in prompt firing
      of a transient, followed by suppression of the generation and synchronization of
      spontaneously occurring transients. It was possible to trigger transients during
      the suppressive phase by raising the concentration of ATP. The dual action of ATP
      was mimicked by ADP or 2-methylthio-ATP but not by AMP or UTP. The number of
      spontaneous transients and their synchronization were reduced in the presence of
      the dephosphorylating agent apyrase. Additional evidence that intermittent
      release of ATP participates in the generation of spontaneous Ca2+ transients was
      obtained from the suppression observed from use of antagonists of the
      purinoceptors [suramin (0.3-30 microM), pyridoxalphosphate-6-azophenyl-2,4
      disulfonic acid (PPADS; 10-30 microM) and 2-deoxy-N-methyladenosine (MRS 2179;
      0.3-30 microM)] or from counteracting beta-cell release of ATP by inhibiting
      exocytosis with 100 nM epinephrine, 100 nM somatostatin, or lowering the
      temperature below 30 degrees C. The data indicate that ATP has time-dependent
      actions (prompt stimulation followed by inhibition) on the generation of Ca2+
      transients mediated by P2Y receptors. It is proposed that beta-cells both receive
      a neural ATP signal with coordinating effects on their Ca2+ oscillations and
      propagate this message to adjacent cells via intermittent release of ATP combined
      with gap junction coupling.

PMID- 14722026
TI  - Preserved direct hepatic insulin action in rats with diet-induced hepatic
      steatosis.
AB  - Recent in vivo studies have demonstrated a strong negative correlation between
      liver triglyceride content and hepatic insulin sensitivity, but a causal
      relationship remains to be established. We therefore have examined parameters of
      direct hepatic insulin action on isolated steatotic livers from high-fat (HF)-fed
      rats compared with standard chow (SC)-fed controls. Direct hepatic action of
      insulin was assayed in Wistar rats after 6 wk of HF diet by measuring the insulin
      induced suppression of epinephrine-induced hepatic glucose output in an isolated
      liver perfusion system. Insulin-induced activation of glycogen synthase was
      measured by quantifying the incorporation of radioactive UDP-glucose into
      glycogen in HF and SC liver lysates. HF diet induced visceral obesity, mild
      insulin resistance, and hepatic steatosis. Both suppression of epinephrine
      induced glycogenolysis and activation of glycogen synthase by insulin were
      sustained in HF rats; no significant difference from SC controls could be
      detected. In conclusion, in our model, triglyceride accumulation into the liver
      was not sufficient to impair direct hepatic insulin action. The data argue for an
      important role of systemic factors in the regulation of hepatic glucose output
      and hepatic insulin sensitivity in vivo.

PMID- 14722027
TI  - Selective stimulation of G-6-Pase catalytic subunit but not G-6-P transporter
      gene expression by glucagon in vivo and cAMP in situ.
AB  - We recently compared the regulation of glucose-6-phosphatase (G-6-Pase) catalytic
      subunit and glucose 6-phosphate (G-6-P) transporter gene expression by insulin in
      conscious dogs in vivo (Hornbuckle LA, Edgerton DS, Ayala JE, Svitek CA, Neal DW,
      Cardin S, Cherrington AD, and O'Brien RM. Am J Physiol Endocrinol Metab 281: E713
      E725, 2001). In pancreatic-clamped, euglycemic conscious dogs, a 5-h period of
      hypoinsulinemia led to a marked increase in hepatic G-6-Pase catalytic subunit
      mRNA; however, G-6-P transporter mRNA was unchanged. Here, we demonstrate, again
      using pancreatic-clamped, conscious dogs, that glucagon is a candidate for the
      factor responsible for this selective induction. Thus glucagon stimulated G-6
      Pase catalytic subunit but not G-6-P transporter gene expression in vivo.
      Furthermore, cAMP stimulated endogenous G-6-Pase catalytic subunit gene
      expression in HepG2 cells but had no effect on G-6-P transporter gene expression.
      The cAMP response element (CRE) that mediates this induction was identified
      through transient transfection of HepG2 cells with G-6-Pase catalytic subunit
      chloramphenicol acetyltransferase fusion genes. Gel retardation assays
      demonstrate that this CRE binds several transcription factors including CRE
      binding protein and CCAAT enhancer-binding protein.

PMID- 14722028
TI  - Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha,
      and FFAs to low-dose endotoxemia in humans.
AB  - Insulin therapy to maintain euglycemia increases survival in critically ill
      patients. To explore possible mechanisms of action, we investigated the effect of
      endotoxin on circulating cytokines, free fatty acids (FFA), and leukocytes during
      manipulated plasma glucose and insulin concentrations. Ten volunteers underwent
      three trials each, receiving an intravenous bolus of endotoxin (0.2 ng/kg) during
      normoglycemia (trial A, control), during a hyperglycemic clamp at 15 mM (trial
      B), and during a hyperinsulinemic euglycemic clamp (trial C). Endotoxin induced
      an increase in neutrophil count, a decrease in lymphocyte count, and an increase
      in serum levels of TNF-alpha, IL-6, and FFA. There was no difference in the TNF
      response between the three trials; the IL-6 levels were increased during the late
      phase of trials B and C compared with trial A. The endotoxin-induced elevation in
      FFA in trial A was suppressed during trials B and C. Clamping (trials B and C)
      caused a reduction in lymphocyte count that persisted after endotoxin injection.
      We conclude that low-dose endotoxemia triggers a subclinical inflammatory
      response and an elevation in FFA. The finding that high insulin serum
      concentrations induce a more prolonged increase in the anti-inflammatory cytokine
      IL-6 and suppress the levels of FFA suggests that insulin treatment of patients
      with sepsis may exert beneficial effects by inducing anti-inflammation and
      protection against FFA toxicity, and thereby inhibit FFA-induced insulin
      resistance.

PMID- 14722029
TI  - Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic
      and respiratory acidosis in the dog.
AB  - Recently, we showed that both acute metabolic acidosis and respiratory acidosis
      stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the
      specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value.
      Because iCa values normally increase during acute acidosis, we now have studied
      the PTH response to acute metabolic and respiratory acidosis in dogs in which the
      iCa concentration was allowed to increase (nonclamped) compared with dogs with a
      normal iCa concentration (clamped). Five groups of dogs were studied: control,
      metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped)
      acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was
      progressively induced during 60 min. In the two clamped groups, iCa was
      maintained at a normal value with an EDTA infusion. Both metabolic and
      respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In
      metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05)
      than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained
      constant despite further pH reductions. The increase in PTH values was greater (P
      < 0.05) in clamped than in nonclamped groups (metabolic and respiratory
      acidosis). In the nonclamped metabolic acidosis group, PTH values first increased
      and then decreased from peak values when iCa increased by > 0.1 mM. In the
      nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline
      values only after iCa values stopped increasing at a pH of 7.30. For the same
      increase in iCa in the nonclamped groups, PTH values increased more in metabolic
      acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis
      stimulate PTH secretion; 2) the physiological increase in the iCa concentration
      during the induction of metabolic and respiratory acidosis reduces the magnitude
      of the PTH increase; 3) in metabolic acidosis, the increase in the iCa
      concentration can be of sufficient magnitude to reverse the increase in PTH
      values; and 4) for the same degree of acidosis-induced hypercalcemia, the
      increase in PTH values is greater in metabolic than in respiratory acidosis.

PMID- 14722030
TI  - Upregulation of angiotensin II type 2 receptor expression in estrogen-induced
      pituitary hyperplasia.
AB  - Recent evidence shows that reexpression and upregulation of angiotensin II (ANG
      II) type 2 (AT2) receptor in adult tissues occur during pathological conditions
      such as tissue hyperplasia, inflammation, and remodeling. In particular,
      expression of functional AT2 receptors in the pituitary and their physiological
      significance and regulation have not been described. In this study, we
      demonstrate that chronic in vivo estrogen treatment, which induces pituitary
      hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR)
      concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo
      progesterone treatment of estrogen-induced pituitary hyperplasia did not modify
      either the ANG II receptor subtype expression pattern or octapeptide-induced and
      AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the
      ANG II prolactin-releasing effect was observed in this group, and this response
      was sensitive to both AT1 and AT2 receptor antagonists. These data are the first
      to document that ANG II can act at the pituitary level through the AT2 receptor
      subtype and that estrogens display a differential regulation of AT1 and AT2
      receptors at this level.

PMID- 14722031
TI  - Extra-adipocyte leptin release in human obesity and its relation to
      sympathoadrenal function.
AB  - The link between the human sympathoadrenalmedullary system and the adipocyte
      hormone leptin is controversial. We measured total and regional norepinephrine
      spillover, epinephrine secretion rate, and extra-adipocyte leptin release in 22
      lean [body mass index (BMI) < 26] and 20 obese (BMI > 28) normotensive men who
      underwent arterial and central venous catheterization. Because plasma clearance
      of leptin is primarily by renal removal, for men at steady state we could
      estimate whole body leptin release to plasma from renal plasma leptin extraction.
      Whole body leptin release was 1,950 +/- 643 (means +/- SE) ng/min in obese men
      and 382 +/- 124 ng/min in lean men (P < 0.05). Total and renal norepinephrine
      spillover rates correlated directly with whole body leptin secretion rate. Leptin
      is released from multiple nonadipocyte sites, which we tested by use of
      simultaneous arteriovenous blood sampling. We found a surprisingly large
      contribution of brain leptin release to the plasma leptin pool, 529 +/- 175
      ng/min (> 40% whole body leptin release), with greater leptin release in obese
      than in lean men, 935 +/- 321 vs. 160 +/- 59 ng/min (P = 0.045). In parallel with
      leptin measurements, we also quantified brain serotonin turnover and jugular
      overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese
      than in lean men, 227 +/- 112 vs. 21 +/- 14 ng/min (P = 0.019), as was overflow
      of NPY from the brain, 12.9 +/- 1.4 vs. 5.3 +/- 2.2 ng/min (P = 0.042). These
      results suggest that leptin is released within the brain and at an increased rate
      in obese humans, in whom activation of brain serotonergic and NPY mechanisms also
      exists.

PMID- 14722032
TI  - Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts:
      role of c-Jun NH2-terminal kinase and histone deacetylase activity.
AB  - Although an individual's genetic makeup is a major determinant of muscle mass,
      other influences, such as hormones, cytokines, nutrition, and exercise can also
      modulate muscle size. IL-6 is an important inflammatory cytokine. Mice that
      overexpress IL-6 fail to thrive and/or have reduced skeletal muscle mass. The
      purpose of the present study was to determine whether the stress hormone
      epinephrine increases inflammatory cytokine expression in skeletal muscle and
      muscle cells. Infusion of epinephrine in vivo for 2 h increased IL-6 protein (15
      fold) and mRNA (40-fold) in skeletal muscle but not in liver. Epinephrine had a
      similar effect in C2C12 muscle cells, where the hormone increased IL-6 protein
      and mRNA in a dose- and time-dependent manner. Epinephrine-stimulated IL-6
      expression was attenuated by the alpha-adrenergic receptor antagonist
      phentolamine and completely blocked by either the beta1/2-adrenergic receptor
      antagonist propranalol or the beta2-antagonist ICI-118551. The transcriptional
      inhibitor DRB and the synthetic glucocorticoid dexamethasone also blocked
      epinephrine-induced IL-6. SP-600125 (a JNK inhibitor) and SB-202190 (a p38 MAP
      kinase inhibitor) completely blocked epinephrine-induced IL-6 synthesis.
      Endotoxin and epinephrine given together had a synergistic affect on IL-6 mRNA
      and protein expression. Trichostatin A (a histone deacetylase inhibitor) blocked
      both endotoxin- and epinephrine-induced IL-6 expression. These data suggest that
      epinephrine induces IL-6 synthesis in skeletal muscle in vivo and myocytes in
      vitro. Epinephrine utilizes predominantly the beta1/2-adrenergic receptors to
      stimulate IL-6 synthesis. Endotoxin and epinephrine synergize to increase IL-6
      mRNA expression. Optimal IL-6 synthesis may require both stress kinase and
      histone deacetylase activity.

PMID- 14722033
TI  - Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus
      cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese
      Taxotere Lung Cancer Study Group.
AB  - PURPOSE: Few randomized trials have demonstrated survival benefit of combination
      chemotherapy involving new agents plus cisplatin compared with classic
      combination chemotherapy in advanced non-small-cell lung cancer (NSCLC). The
      primary aim of this study was to test whether docetaxel plus cisplatin (DC)
      improves survival compared with vindesine plus cisplatin (VdsC) in patients with
      previously untreated stage IV NSCLC. PATIENTS AND METHODS: Eligible, stage IV,
      chemotherapy-naive patients (n = 311) were randomly assigned to receive docetaxel
      60 mg/m(2) intravenously on day 1 plus cisplatin 80 mg/m(2) intravenously on day
      1 of a 3- or 4-week cycle, or vindesine 3 mg/m(2) intravenously on days 1, 8, and
      15 plus cisplatin 80 mg/m(2) intravenously on day 1 of a 4-week cycle. Cross-over
      administration of docetaxel and vindesine was prohibited for both treatment
      groups. RESULTS: Overall, 302 patients were eligible for evaluation. The DC arm
      demonstrated significant improvements compared with the VdsC arm in overall
      response rates (37% v 21%, respectively; P <.01) and median survival times (11.3
      v 9.6 months, respectively; P =.014). Two-year survival rates were 24% for the DC
      arm compared with 12% for the VdsC arm. The physical domain of the Quality of
      Life for Cancer Patients Treated with Anticancer Drugs measure was significantly
      better in the DC arm than in the VdsC arm (P =.020). Toxicity was predominantly
      hematologic and was more severe in the VdsC arm. CONCLUSION: As first-line
      treatment for stage IV NSCLC, DC resulted in greater clinical benefit in terms of
      response rate (with marked improvements in overall and 2-year survival rates) and
      quality of life than did treatment with VdsC.

PMID- 14722034
TI  - Outcome of elderly patients with recurrent or metastatic head and neck cancer
      treated with cisplatin-based chemotherapy.
AB  - PURPOSE: To evaluate the outcome of elderly patients with head and neck cancer
      undergoing palliative chemotherapy. PATIENTS AND METHODS: We analyzed combined
      data from two mature phase III randomized trials conducted by the Eastern
      Cooperative Oncology Group (ECOG; trial E1393, which compared cisplatin plus
      paclitaxel at two dose levels, and trial E1395, which compared cisplatin plus
      fluorouracil to cisplatin plus paclitaxel) to evaluate the toxicity, objective
      response rates, and survival of patients 70 years or older versus their younger
      counterparts. All patients had previously untreated recurrent or metastatic
      squamous cell carcinoma of the head and neck and ECOG performance status 0 or 1.
      RESULTS: Fifty-three elderly patients were enrolled from a total of 399 eligible
      participants (13%). Elderly patients had similar objective response rates (28% v
      33%) and median time to progression (5.25 v 4.8 months) compared with younger
      patients. The median survival was 5.3 v 8 months (Wilcoxon P =.06; log-rank P
      =.17) and the 1-year survival 26% v 33% for elderly and younger patients,
      respectively. Elderly patients had a significantly higher incidence of severe
      nephrotoxicity, diarrhea, and thrombocytopenia. A higher rate of toxic deaths was
      noted in the elderly but did not reach statistical significance (13% v 8%; P
      =.29). CONCLUSION: Elderly patients were underrepresented in these studies. Fit
      elderly patients with recurrent or metastatic head and neck cancer sustained
      increased toxicities with cisplatin-based doublets but had comparable survival
      outcomes compared with younger patients. Strategies to ameliorate toxicities
      should be pursued in the elderly.

PMID- 14722035
TI  - Phase III study of N,N-diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine (BMS-217380
      01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent
      breast cancer: National Cancer Institute of Canada Clinical Trials Group Study
      MA.19.
AB  - PURPOSE: N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is
      a novel agent that augments chemotherapy cytotoxicity in vitro and in vivo. A
      phase II trial combining DPPE and doxorubicin (DOX) in metastatic breast
      carcinoma showed increased response over that expected with DOX. We report a
      phase III trial comparing DOX with DPPE plus DOX in metastatic or recurrent
      breast cancer. PATIENTS AND METHODS: Anthracycline-naive women with measurable
      metastatic disease were randomly assigned to receive, every 21 days, either DOX
      60 mg/m(2) intravenously or DOX during the last 20 minutes of an 80-minute
      infusion of DPPE (5.3 mg/kg), in both cases to cumulative DOX doses of 450
      mg/m(2). Patients receiving DPPE were aggressively premedicated to ameliorate
      toxicity. End points included progression-free survival (PFS), response rate
      (RR), and response duration (RD), quality of life (QOL), toxicity, and overall
      survival (OS). RESULTS: A planned interim analysis failed to detect an RR
      difference more than 5%. The study was closed to additional accrual and all DPPE
      was discontinued. The final analysis was conducted as planned after 256
      progression events (median follow-up, 20.5 months). There was no significant
      difference in RR, RD, or PFS between arms. DPPE plus DOX was statistically
      superior to DOX in OS (hazard ratio, 0.66; 95% CI, 0.48 to 0.91; P =.021). DPPE
      plus DOX was associated with more gastrointestinal and CNS toxicity. No
      consistent influence on QOL was detected. CONCLUSION: This study demonstrated no
      advantage in RR, RD, or PFS but significantly superior OS for DPPE plus DOX.
      Additional studies of DPPE are warranted.

PMID- 14722036
TI  - Prospective multicenter study of axillary nodal staging by positron emission
      tomography in breast cancer: a report of the staging breast cancer with PET Study
      Group.
AB  - PURPOSE: To determine the accuracy of positron emission tomography with fluorine
      18-labeled 2-fluoro-2-deoxy-d-glucose (FDG-PET) in detecting axillary nodal
      metastases in women with primary breast cancer. PATIENTS AND METHODS: In this
      prospective multicenter study, 360 women with newly diagnosed invasive breast
      cancer underwent FDG-PET. Images were blindly interpreted by three experienced
      readers for abnormally increased axillary FDG uptake. Imaging results from 308
      assessable axillae were compared with axillary node pathology. RESULTS: For
      detecting axillary nodal metastasis, the mean estimated area under the receiver
      operator curve for the three readers was 0.74 (range, 0.70 to 0.76). If at least
      one probably or definitely abnormal axillary focus was considered positive, the
      mean (and range) sensitivity, specificity, and positive and negative predictive
      values for PET were 61% (54% to 67%), 80% (79% to 81%), 62% (60% to 64%), and 79%
      (76% to 81%), respectively. False-negative axillae on PET had significantly
      smaller and fewer tumor-positive lymph nodes (2.7) than true-positive axillae
      (5.1; P <.005). Semiquantitative analysis of axillary FDG uptake showed that a
      nodal standardized uptake value (lean body mass) more than 1.8 had a positive
      predictive value of 90%, but a sensitivity of only 32%. Finding two or more
      intense foci of tracer uptake in the axilla was highly predictive of axillary
      metastasis (78% to 83% positive predictive value), albeit insensitive (27%).
      CONCLUSION: FDG-PET has moderate accuracy for detecting axillary metastasis but
      often fails to detect axillae with small and few nodal metastases. Although
      highly predictive for nodal tumor involvement when multiple intense foci of
      tracer uptake are identified, FDG-PET is not routinely recommended for axillary
      staging of patients with newly diagnosed breast cancer.

PMID- 14722037
TI  - BRAF gene is somatically mutated but does not make a major contribution to
      malignant melanoma susceptibility: the Italian Melanoma Intergroup Study.
AB  - PURPOSE: Ocogenic activation of the BRAF gene has been demonstrated to be
      involved in the pathogenesis of malignant melanoma (MM). In this study, we
      investigated the contribution of BRAF to melanoma susceptibility, also making a
      comparison with frequency of CDKN2A germline mutations in MM patients from
      different areas in Italy. PATIENTS AND METHODS: sing a combination of denaturing
      high-performance liquid chromatography analysis and automated sequencing on
      genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211
      from northern Italy and 358 from southern Italy) were screened for BRAF
      mutations. RESULTS: Three BRAF germline sequence variants (M116R, V599E, and
      G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF
      mutation, V599E, was detected in one germline DNA sample only; M116R and G608H
      were newly described mutations. A high frequency (59%) of BRAF mutations was
      instead observed in tumor samples from patients also undergoing germline DNA
      analysis; at the somatic level, substitution of valine 599 was found to account
      for the majority (88%) of BRAF mutations. We then estimated the germline mutation
      rates in BRAF and CDKN2A among 358 consecutively collected patient samples
      originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of
      CDKN2A and BRAF mutations, respectively, was detected. CONCLUSION: utation
      analysis of either blood DNA from a large collection of MM patients or matched MM
      tissues from a subset of such patients revealed that BRAF is somatically mutated
      and does not play a major role in melanoma susceptibility. The present study
      further suggests that patient origin may account for different mutation rates in
      candidate genes.

PMID- 14722038
TI  - Octreotide alone or with prednisone in patients with advanced thymoma and thymic
      carcinoma: an Eastern Cooperative Oncology Group Phase II Trial.
AB  - PURPOSE: To determine the objective response rate, duration of remission and
      toxicity of octreotide alone or with the later addition of prednisone in patients
      with unresectable, advanced thymic malignancies in whom the pretreatment
      octreotide scan was positive. PATIENTS AND METHODS: Forty-two patients with
      advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were
      fully assessable (one patient had inconclusive histology; three patients had
      negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously
      tid. At 2 months, patients were evaluated. Responding patients continued to
      receive octreotide alone; patients with progressive disease were removed from the
      study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1
      year. RESULTS: Two complete (5.3%) and 10 partial responses (25%) were observed
      (four partial responses with octreotide alone; the remainder with octreotide plus
      prednisone). None of the six patients without pure thymoma responded. The 1- and
      2-year survival rates were 86.6% and 75.7%, respectively. Patients with an
      Eastern Cooperative Oncology Group performance status of 0 lived significantly
      longer than did those with a performance status of 1 (P =.031). CONCLUSION:
      Octreotide alone has modest activity in patients with octreotide scan-positive
      thymoma. Prednisone improves the overall response rate but is associated with
      increased toxicity. Additional studies with the agent are warranted.

PMID- 14722039
TI  - Percutaneous image-guided radiofrequency ablation of painful metastases involving
      bone: a multicenter study.
AB  - PURPOSE: Few options are available for pain relief in patients with bone
      metastases who fail standard treatments. We sought to determine the benefit of
      radiofrequency ablation (RFA) in providing pain relief for patients with
      refractory pain secondary to metastases involving bone. PATIENTS AND METHODS:
      Thirty-one US and 12 European patients with painful osteolytic metastases
      involving bone were treated with image-guided RFA using a multitip needle.
      Treated patients had > or = 4/10 pain and had either failed or were poor
      candidates for standard treatments such as radiation or opioid analgesics. Using
      the Brief Pain Inventory-Short Form, worst pain intensity was the primary end
      point, with a 2-unit drop considered clinically significant. RESULTS: Forty-three
      patients were treated (median follow-up, 16 weeks). Before RFA, the mean score
      for worst pain was 7.9 (range, 4/10 to 10/10). Four, 12, and 24 weeks following
      treatment, worst pain decreased to 4.5 (P <.0001), 3.0 (P <.0001), and 1.4 (P
      =.0005), respectively. Ninety-five percent (41 of 43 patients) experienced a
      decrease in pain that was considered clinically significant. Opioid usage
      significantly decreased at weeks 8 and 12. Adverse events were seen in 3 patients
      and included (1) a second-degree skin burn at the grounding pad site, (2)
      transient bowel and bladder incontinence following treatment of a metastasis
      involving the sacrum, and (3) a fracture of the acetabulum following RFA of an
      acetabular lesion. CONCLUSION: RFA of painful osteolytic metastases provides
      significant pain relief for cancer patients who have failed standard treatments.

PMID- 14722040
TI  - The attitudes of cancer patients and their families toward the disclosure of
      terminal illness.
AB  - PURPOSE: To ascertain the attitude of cancer patients and their families toward
      disclosure of terminal illness to the patient. PATIENTS AND METHODS: We
      constructed a questionnaire that included demographic and clinical information
      and delivered it to 758 consecutive individuals (433 cancer patients and 325
      families that have a relative with cancer) at seven university hospitals and one
      national cancer center in Korea. RESULTS: 380 cancer patients and one member from
      each of 281 families that have a relative with cancer completed the
      questionnaire. Cancer patients were more likely than family members to believe
      that patients should be informed of the terminal illness (96.1% v 76.9%; P
      <.001). Fifty percent of the family members and 78.3% of the patients thought
      that the doctor in charge should be the one who informs the patient.
      Additionally, 71.7% of the patients and 43.6% of the family members thought that
      patients should be informed immediately after the diagnosis. Stepwise multiple
      logistic regression indicated that the patient group was more likely than the
      family group to want the patient to be informed of the terminal illness (odds
      ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61
      to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41).
      CONCLUSION: Our findings indicated that most cancer patients want to be informed
      if their illness is terminal, and physicians should realize that the patient and
      the family unit may differ in their attitude toward such a disclosure. Our
      results also reflect the importance of how information is given to the patient.

PMID- 14722041
TI  - Trends in the aggressiveness of cancer care near the end of life.
AB  - PURPOSE: To characterize the aggressiveness of end-of-life cancer treatment for
      older adults on Medicare, and its relationship to the availability of healthcare
      resources. PATIENTS AND METHODS: We analyzed Medicare claims of 28,777 patients
      65 years and older who died within 1 year of a diagnosis of lung, breast,
      colorectal, or other gastrointestinal cancer between 1993 and 1996 while living
      in one of 11 US regions monitored by the Surveillance, Epidemiology, and End
      Results Program. RESULTS: Rates of treatment with chemotherapy increased from
      27.9% in 1993 to 29.5% in 1996 (P =.02). Among those who received chemotherapy,
      15.7% were still receiving treatment within 2 weeks of death, increasing from
      13.8% in 1993 to 18.5% in 1996 (P <.001). From 1993 to 1996, increasing
      proportions of patients had more than one emergency department visit (7.2% v
      9.2%; P <.001), hospitalization (7.8% v 9.1%; P =.008), or were admitted to an
      intensive care unit (7.1% v 9.4%; P =.009) in the last month of life. Although
      fewer patients died in acute-care hospitals (32.9% v 29.5%; P <.001) and more
      used hospice services (28.3% v 38.8%; P <.001), an increasing proportion of
      patients who received hospice care initiated this service only within the last 3
      days of life (14.3% v 17.0%; P =.004). Black patients were more likely than white
      patients to experience aggressive intervention in nonteaching hospitals but not
      in teaching hospitals. Greater local availability of hospices was associated with
      less aggressive treatment near death on multivariate analysis. CONCLUSION: The
      treatment of cancer patients near death is becoming increasingly aggressive over
      time.

PMID- 14722042
TI  - Clinical cardiac tolerability of trastuzumab.
AB  - PURPOSE: This review provides an update on the current understanding of the
      clinical cardiac tolerability of trastuzumab, a humanized monoclonal antibody
      effective in the treatment of patients with advanced breast cancer overexpressing
      or amplifying HER2. METHODS AND RESULTS: We produced a summary of currently
      available information regarding the incidence and natural history of trastuzumab
      associated cardiac dysfunction. Data from new, prospective clinical studies that
      incorporate close cardiac monitoring and standardized follow-up in patients with
      either advanced or earlier stages of breast cancer are also presented, and
      hypotheses regarding potential mechanisms of trastuzumab-related cardiotoxicity
      are discussed. Patients treated with trastuzumab in the pivotal trials were found
      to have increased risk for cardiac dysfunction, mostly when used concurrent with
      anthracyclines. Recent trials have required more stringent and consistent cardiac
      monitoring criteria and excluded patients with abnormal cardiac function, pre
      existing heart disease, and/or high cumulative doses of anthracyclines. Decreases
      of ejection fraction and a few cases of congestive heart failure (CHF) requiring
      medical therapy have been detected. Improvements in ejection fraction and the
      symptoms of CHF have been subsequently noted in a significant number of these
      patients. CONCLUSION: Trastuzumab is associated with an increased risk of
      asymptomatic decreases in ejection fraction, and, in a small number of patients,
      CHF that is almost always responsive to medical management. This risk is greatest
      in patients receiving concurrent anthracyclines. More data are needed to help
      elucidate the pathophysiology of this syndrome.

PMID- 14722043
TI  - Quality of life among disease-free survivors of rectal cancer.
AB  - PURPOSE: To identify factors affecting the quality of life (QoL) of disease-free
      survivors of rectal cancer. PATIENTS AND METHODS: One hundred twenty-one patients
      in complete remission more than 2 years after diagnosis were asked to complete
      three QoL questionnaires: the European Organization for Research and Treatment of
      Cancer (EORTC) QLQ-C30; its colorectal module, QLQ-CR38; and the Duke generic
      instrument. RESULTS: Patients reported less pain (P =.002) than did controls
      drawn from the general population. EORTC QLQ-C30 physical scores were also higher
      among rectal cancer survivors than in the general Norwegian or German population
      (P =.0005 and P =.002, respectively). Unexpectedly, stoma patients reported
      better social functioning than did nonstoma patients (P =.005), with less anxiety
      (P =.008) and higher self-esteem (P =.0002). In the present authors' experience,
      the QLQ-CR38 does not discriminate between these groups. Residual abdominal or
      pelvic pain and constipation had the most negative influence on QoL. CONCLUSION:
      QoL is high among rectal cancer survivors, including stoma patients. Simultaneous
      use of several QoL questionnaires appears to have value in follow-up and in
      monitoring the effects of therapy. The impact of residual pain and constipation
      on long-term QoL should be considered when establishing a treatment regimen.

PMID- 14722045
TI  - Complications of malignancy: case 1. Systemic tumor embolism from lung cancer at
      presentation.

PMID- 14722044
TI  - The role of signal transducer and activator of transcription factors in
      leukemogenesis.
AB  - Human leukemias are frequently associated with the aberrant expression of
      activated fusion tyrosine kinases or activated protein tyrosine kinases carrying
      insertional or point mutations. The activated kinase enzymes typically
      phosphorylate one or more signal transducer and activator of transcription (STAT)
      factors, which translocate to the cell nucleus and regulate the expression of
      genes associated with survival and proliferation. The phosphorylation and
      activation of STAT family members has been described in a wide range of human
      leukemias. Furthermore, animal models of leukemia have demonstrated the pivotal
      contribution of STAT activation to leukemic pathogenesis. This review discusses
      evidence for the functional importance of STAT activation in the biology of
      leukemia and current opportunities for modulating STAT proteins in the therapy of
      this group of diseases.

PMID- 14722046
TI  - Complications of malignancy: case 2. Infectious tissue pneumatosis as a result of
      colon cancer perforation in a survivor of Hodgkin's disease.

PMID- 14722047
TI  - Complications of malignancy: case 3. Chronic lymphocytic leukemia presenting with
      panhypopituitarism.

PMID- 14722048
TI  - Cisplatin and fluorouracil concurrent to radiotherapy in nasopharyngeal cancer:
      is the schedule compatible?

PMID- 14722050
TI  - What is "appropriate" care for ovarian cancer?

PMID- 14722051
TI  - The prognostic significance of indium-111-capromab penetide.

PMID- 14722054
TI  - Inflammatory breast carcinoma: the sphinx of breast cancer research.

PMID- 14722055
TI  - Water intake and cancer prevention.

PMID- 14722057
TI  - The Tim8-Tim13 complex of Neurospora crassa functions in the assembly of proteins
      into both mitochondrial membranes.
AB  - The Tim8 and Tim13 proteins in yeast are known to exist in the mitochondrial
      intermembrane space and to form a hetero-oligomeric complex involved in the
      import of the mitochondrial inner membrane protein Tim23, the central component
      of the TIM23 translocase. Here, we have isolated tim8 and tim13 mutants in
      Neurospora crassa and have shown that mitochondria lacking the Tim8-Tim13 complex
      were deficient in the import of the outer membrane beta-barrel proteins Tom40 and
      porin. Cross-linking studies showed that the Tom40 precursor contacts the Tim8
      Tim13 complex. The complex is involved at an early point in the Tom40 assembly
      pathway because cross-links can only be detected during the initial stages of
      Tom40 import. In mitochondria lacking the Tim8-Tim13 complex, the Tom40 precursor
      appears in a previously characterized early intermediate of Tom40 assembly more
      slowly than in wild type mitochondria. Thus, our data suggest a model in which
      one of the first steps in Tom40 assembly may be interaction with the Tim8-Tim13
      complex. As in yeast, the N. crassa Tim23 precursor was imported inefficiently
      into mitochondria lacking the Tim8-Tim13 complex when the membrane potential was
      reduced. Tim23 import intermediates could also be cross-linked to the complex,
      suggesting a dual role for the Tim8-Tim13 intermembrane space complex in the
      import of proteins found in both the outer and inner mitochondrial membranes.

PMID- 14722058
TI  - Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel
      disease. Evidence for involvement of the transcription factor Egr-1.
AB  - Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of
      cyclooxygenase-derived prostaglandin (PG) H(2) to PGE(2). Increased amounts of
      mPGES-1 were detected in inflamed intestinal mucosa from patients with
      inflammatory bowel disease (IBD). Treatment with tumor necrosis factor (TNF)
      alpha stimulated mPGES-1 transcription in human colonocytes, resulting in
      increased amounts of mPGES-1 mRNA and protein. The inductive effect of TNF-alpha
      localized to the GC box region of the mPGES-1 promoter. Binding of Egr-1 to the
      GC box region of the mPGES-1 promoter was enhanced by treatment with TNF-alpha.
      Notably, increased Egr-1 expression and binding activity were also detected in
      inflamed mucosa from IBD patients. Treatment with TNF-alpha induced the
      activities of phosphatidylcholine-phospholipase C (PC-PLC) and protein kinase
      (PK) C and enhanced NO production. A pharmacological approach was used to
      implicate PC-PLC --> PKC --> NO signaling as being important for the induction of
      mPGES-1 by TNF-alpha. TNF-alpha also enhanced guanylate cyclase activity and
      inhibitors of guanylate cyclase activity blocked the induction of mPGES-1 by TNF
      alpha. YC-1, an activator of guanylate cyclase, induced mPGES-1. Overexpressing a
      dominant negative form of PKG blocked TNF-alpha-mediated stimulation of the mPGES
      1 promoter. Taken together, these results suggest that overexpression of mPGES-1
      in IBD is the result of Egr-1-mediated activation of transcription. Moreover, TNF
      alpha induced mPGES-1 by stimulating PC-PLC --> PKC --> NO --> cGMP --> PKG
      signal transduction pathway.

PMID- 14722059
TI  - Overexpression of CUG triplet repeat-binding protein, CUGBP1, in mice inhibits
      myogenesis.
AB  - Accumulation of RNA CUG repeats in myotonic dystrophy type 1 (DM1) patients leads
      to the induction of a CUG-binding protein, CUGBP1, which increases translation of
      several proteins that are required for myogenesis. In this paper, we examine the
      role of overexpression of CUGBP1 in DM1 muscle pathology using transgenic mice
      that overexpress CUGBP1 in skeletal muscle. Our data demonstrate that the
      elevation of CUGBP1 in skeletal muscle causes overexpression of MEF2A and p21 to
      levels that are significantly higher than those in skeletal muscle of wild type
      animals. A similar induction of these proteins is observed in skeletal muscle of
      DM1 patients with increased levels of CUGBP1. Immunohistological analysis showed
      that the skeletal muscle from mice overexpressing CUGBP1 is characterized by a
      developmental delay, muscular dystrophy, and myofiber-type switch: increase of
      slow/oxidative fibers and the reduction of fast fibers. Examination of molecular
      mechanisms by which CUGBP1 up-regulates MEF2A shows that CUGBP1 increases
      translation of MEF2A via direct interaction with GCN repeats located within MEF2A
      mRNA. Our data suggest that CUGBP1-mediated overexpression of MEF2A and p21
      inhibits myogenesis and contributes to the development of muscle deficiency in
      DM1 patients.

PMID- 14722060
TI  - Binding of SecA to the SecYEG complex accelerates the rate of nucleotide exchange
      on SecA.
AB  - SecYEG translocase mediates the transport of preproteins across the inner
      membrane of Escherichia coli. SecA binds the membrane-embedded SecYEG protein
      conducting channel with high affinity and then drives the stepwise translocation
      of preproteins across the membrane through multiple cycles of ATP binding and
      hydrolysis. We have investigated the kinetics of nucleotide binding to SecA while
      associated with the SecYEG complex. Lipid-bound SecA was separated from Se-cYEG
      bound SecA by sedimentation of the proteoliposomes through a glycerol cushion,
      which maintains the SecA native state and effectively removes the lipid-bound
      SecA fraction. Nucleotide binding was assessed by means of fluorescence resonance
      energy transfer using fluorescent ATP analogues as acceptors of the intrinsic
      SecA tryptophan fluorescence in the presence of a tryptophanless variant of the
      SecYEG complex. Binding of SecA to the SecYEG complex elevated the rate of
      nucleotide exchange at SecA independently of the presence of preprotein. This
      defines a novel pretranslocation activated state of SecA that is primed for ATP
      hydrolysis upon preprotein interaction.

PMID- 14722061
TI  - In vitro suppression of the lipogenic pathway by the nonnucleoside reverse
      transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes.
AB  - A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central
      adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients
      receiving highly active antiretroviral therapy. The aim of this work was to
      examine the effects of the nonnucleoside reverse transcriptase inhibitor (NNRTI)
      efavirenz on adipocyte differentiation and metabolism. When induced to
      differentiate in the presence of efavirenz (5-50 microm), 3T3-F442A preadipocytes
      failed to accumulate cytoplasmic triacylglycerol droplets. This phenomenon was
      rapidly reversible and was also readily detectable in the 3T3-L1 preadipose cell
      line and in primary cultures of human preadipocytes. When applied to mature 3T3
      F442A adipocytes, efavirenz induced a delayed and moderate reduction in cell
      triglyceride content. Measurement of [(3)H]deoxyglucose uptake, basal and agonist
      stimulated lipolysis, and cell viability indicated that these pathways are not
      involved in efavirenz effects on triacylglycerol accumulation. By contrast, we
      found that the NNRTI induced a dramatic dose- and time-dependent decrease in gene
      and protein expression of the lipogenic transcription factor sterol regulatory
      element-binding protein-1c (SREBP-1c). Adipose conversion was only altered at the
      highest efavirenz concentrations, as suggested by the mild reduction in
      peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer-binding
      protein-alpha. CCAAT/enhancer-binding protein-beta remained unchanged. The
      inhibition of SREBP-1c expression was accompanied by a sharp reduction in the
      expression of SREBP-1c target genes and in the adipocyte lipogenic activity in
      efavirenz-treated cells. Finally, the inhibitory effect of efavirenz on cell
      triglyceride accumulation was prevented by directly providing free fatty acids to
      the cells and was reversed by overexpression of a dominant positive form of SREBP
      1c, reinforcing the implication of this transcription factor in the antilipogenic
      effect of the drug. When considered together, these results demonstrate for the
      first time that the NNRTI efavirenz induces a strong inhibition of the SREBP-1c
      dependent lipogenic pathway that might contribute to adipose tissue atrophy.

PMID- 14722062
TI  - Investigating mitochondrial redox potential with redox-sensitive green
      fluorescent protein indicators.
AB  - Current methods for determining ambient redox potential in cells are labor
      intensive and generally require destruction of tissue. This precludes single cell
      or real time studies of changes in redox poise that result from metabolic
      processes or environmental influences. By substitution of surface-exposed
      residues on the Aequorea victoria green fluorescent protein (GFP) with cysteines
      in appropriate positions to form disulfide bonds, reduction-oxidation-sensitive
      GFPs (roGFPs) have been created. roGFPs have two fluorescence excitation maxima
      at about 400 and 490 nm and display rapid and reversible ratiometric changes in
      fluorescence in response to changes in ambient redox potential in vitro and in
      vivo. Crystal structure analyses of reduced and oxidized crystals of roGFP2 at
      2.0- and 1.9-A resolution, respectively, reveal in the oxidized state a highly
      strained disulfide and localized main chain structural changes that presumably
      account for the state-dependent spectral changes. roGFP1 has been targeted to the
      mitochondria in HeLa cells. Fluorometric measurements on these cells using a
      fluorescence microscope or in cell suspension using a fluorometer reveal that the
      roGFP1 probe is in dynamic equilibrium with the mitochondrial redox status and
      responds to membrane-permeable reductants and oxidants. The roGFP1 probe reports
      that the matrix space in HeLa cell mitochondria is highly reducing, with a
      midpoint potential near -360 mV (assuming mitochondrial pH approximately 8.0 at
      37 degrees C). In other work (C. T. Dooley, T. M. Dore, G. Hanson, W. C. Jackson,
      S. J. Remington, and R. Y. Tsien, submitted for publication), it is shown that
      the cytosol of HeLa cells is also unusually reducing but somewhat less so than
      the mitochondrial matrix.

PMID- 14722063
TI  - Fusion-related release of glutamate from astrocytes.
AB  - Although cell culture studies have implicated the presence of vesicle proteins in
      mediating the release of glutamate from astrocytes, definitive proof requires the
      identification of the glutamate release mechanism and the localization of this
      mechanism in astrocytes at synaptic locales. In cultured murine astrocytes we
      show an array of vesicle proteins, including SNARE proteins, and vesicular
      glutamate transporters that are required to fill vesicles with glutamate. Using
      immunocytochemistry and single-cell multiplex reverse transcription-PCR we
      demonstrate the presence of these proteins and their transcripts within
      astrocytes freshly isolated from the hippocampus. Moreover, immunoelectron
      microscopy demonstrates the presence of VGLUT1 in processes of astrocytes of the
      hippocampus. To determine whether calcium-dependent glutamate release is mediated
      by exocytosis, we expressed the SNARE motif of synaptobrevin II to prevent the
      formation of SNARE complexes, which reduces glutamate release from astrocytes. To
      further determine whether vesicular exocytosis mediates calcium-dependent
      glutamate release from astrocytes, we performed whole cell capacitance
      measurements from individual astrocytes and demonstrate an increase in whole cell
      capacitance, coincident with glutamate release. Together, these data allow us to
      conclude that astrocytes in situ express vesicle proteins necessary for filling
      vesicles with the chemical transmitter glutamate and that astrocytes release
      glutamate through a vesicle- or fusion-related mechanism.

PMID- 14722064
TI  - Endocytic adaptor molecules reveal an endosomal population of clathrin by total
      internal reflection fluorescence microscopy.
AB  - Most eukaryotes utilize a single pool of clathrin to assemble clathrin-coated
      transport vesicles at different intracellular locations. Coat assembly is a
      cyclical process. Soluble clathrin triskelia are recruited to the membrane
      surface by compartment-specific adaptor and/or accessory proteins. Adjacent
      triskelia then pack together to assemble a polyhedral lattice that progressively
      invaginates, budding off the membrane surface encasing a nascent transport
      vesicle that is quickly uncoated. Using total internal reflection fluorescence
      microscopy to follow clathrin dynamics close to the cell surface, we find that
      the majority of labeled clathrin structures are relatively static, moving
      vertically in and out of the evanescent field but with little lateral motion. A
      small minority shows rapid lateral and directed movement over micrometer
      distances. Adaptor proteins, including the alpha subunit of AP-2, ARH, and Dab2
      are also relatively static and exhibit virtually no lateral movement. A
      fluorescently labeled AP-2 beta2 subunit, incorporated into both AP-2 and AP-1
      adaptor complexes, exhibits both types of behavior. This suggests that the highly
      motile clathrin puncta may be distinct from plasma membrane-associated clathrin
      structures. When endocytosed cargo molecules, such as transferrin or low density
      lipoprotein, are followed into cells, they exhibit even more lateral motion than
      clathrin, and gradually concentrate in the perinuclear region, consistent with
      classical endosomal trafficking. Importantly, clathrin partially colocalizes with
      internalized transferrin, but diverges as the structures move longitudinally.
      Thus, highly motile clathrin structures are apparently distinct from the plasma
      membrane, accompany transferrin, and contain AP-1, revealing an endosomal
      population of clathrin structures.

PMID- 14722065
TI  - Quantitative determination of direct binding of b subunit to F1 in Escherichia
      coli F1F0-ATP synthase.
AB  - The stator in F(1)F(0)-ATP synthase resists strain generated by rotor torque. In
      Escherichia coli, the b(2)delta subunit complex comprises the stator, bound to
      subunit a in F(0) and to the alpha(3)beta(3) hexagon of F(1). To quantitatively
      characterize binding of b subunit to the F(1) alpha(3)beta(3) hexagon, we
      developed fluorimetric assays in which wild-type F(1), or F(1) enzymes containing
      introduced Trp residues, were titrated with a soluble portion of the b subunit
      (b(ST34-156)). With five different F(1) enzymes, K(d)(b(ST34-156)) ranged from 91
      to 157 nm. Binding was strongly Mg(2+)-dependent; in EDTA buffer, K(d)(b(ST34
      156)) was increased to 1.25 microm. The addition of the cytoplasmic portion of
      the b subunit increases the affinity of binding of delta subunit to delta
      depleted F(1). The apparent K(d)(b(ST34-156)) for this effect was increased from
      150 nm in Mg(2+) buffer to 1.36 microm in EDTA buffer. This work demonstrates
      quantitatively how binding of the cytoplasmic portion of the b subunit directly
      to F(1) contributes to stator resistance and emphasizes the importance of Mg(2+)
      in stator interactions.

PMID- 14722066
TI  - Yeast Nfs1p is involved in thio-modification of both mitochondrial and
      cytoplasmic tRNAs.
AB  - The IscS protein is a pyridoxal phosphate-containing cysteine desulfurase
      involved in iron-sulfur cluster biogenesis. In prokaryotes, IscS is also involved
      in various metabolic functions, including thio-modification of tRNA. By contrast,
      the eukaryotic ortholog of IscS (Nfs1) has thus far been shown to be functional
      only in mitochondrial iron-sulfur cluster biogenesis. We demonstrate here that
      yeast Nfs1p is also required for the post-transcriptional thio-modification of
      both mitochondrial (mt) and cytoplasmic (cy) tRNAs in vivo. Depletion of Nfs1p
      resulted in an immediate impairment of the 2-thio-modification of 5
      carboxymethylaminomethyl-2-thiouridine at the wobble positions of mt
      tRNA(UUU)(Lys) and mt-tRNA(UUG)(Gln). In addition, we observed a severe reduction
      in the 2-thio-modification of 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U)
      of cy-tRNA(UUU)(Lys2) and cy-tRNA(UUC)(Glu3), although the effect was somewhat
      delayed compared with that seen in mt-tRNAs. Mass spectrometry analysis revealed
      an increase in 5-methoxycarbonylmethyluridine concomitant with a decrease in
      mcm(5)s(2)U in cy-tRNAs that were prepared from Nfs1p-depleted cells. These
      results suggest that Nfs1p is involved in the 2-thio-modification of both 5
      carboxymethylaminomethyl-2-thiouridine in mt-tRNAs and mcm(5)s(2)U in cy-tRNAs.

PMID- 14722067
TI  - A natural prothrombin mutant reveals an unexpected influence of A-chain structure
      on the activity of human alpha-thrombin.
AB  - We have recently identified in two unrelated patients with bleeding tendency a
      homozygous mutation causing a deletion of one of the two contiguous
      Lys(9)/Lys(10) residues in the A-chain of alpha-thrombin (DeltaK9). We used in
      vitro expression analysis to clarify the role of the deletion of Lys(9) or
      Lys(10) in the thrombin function. The k(cat)/K(m) value of the hydrolysis by
      DeltaK9 of the synthetic substrate Phe-Pip-Arg-p-nitroanilide (where Pip
      represents l-pipecolyl) and fibrinopeptide A was 18- and 60-fold lower,
      respectively, compared with wild type (WT). Interaction with antithrombin was
      also reduced in the mutant, the association rate being about 20-fold lower than
      in the WT thrombin. The sensitivity to sodium ion of DeltaK9 was found
      significantly attenuated compared with the WT form. DeltaK9 has a very weak
      platelet-activating capacity, attributed to a severely defective PAR1
      interaction, whereas the binding to the platelet glycoprotein Ibalpha was
      unaffected. Likewise, the interaction with protein C was severely impaired,
      whereas interaction with thrombomodulin had a normal K(d) value. At variance with
      these findings, both low affinity (basic pancreatic trypsin inhibitor) and high
      affinity (N-alpha-[2-naphthylsulfonyl-glycyl]-4-amidinophenylalanine-piperidide)
      thrombin inhibitors displayed a better binding to DeltaK9 than to the WT form,
      indicating a better accommodation of these inhibitors into the catalytic pocket
      of DeltaK9. A molecular dynamics simulation of the DeltaK9 thrombin in full
      explicit water solvent provided support to the role of the A-chain in affecting
      conformation and catalytic properties of the B-chain, especially in some
      insertion loops of the enzyme, such as the 60-loop, as well as in the geometry of
      the catalytic triad residues.

PMID- 14722068
TI  - High level expression of human immunodeficiency virus type-1 Vif inhibits viral
      infectivity by modulating proteolytic processing of the Gag precursor at the
      p2/nucleocapsid processing site.
AB  - The human immunodeficiency virus type-1 Vif protein has a crucial role in
      regulating viral infectivity. However, we found that newly synthesized Vif is
      rapidly degraded by cellular proteases. We tested the dose dependence of Vif in
      non-permissive H9 cells and found that Vif, when expressed at low levels,
      increased virus infectivity in a dose-dependent manner. Surprisingly, however,
      the range of Vif required for optimal virus infectivity was narrow, and further
      increases in Vif severely reduced viral infectivity. Inhibition of viral
      infectivity at higher levels of Vif was cell type-independent and was associated
      with an accumulation of Gag-processing intermediates. Vif did not act as a
      general protease inhibitor but selectively inhibited Gag processing at the capsid
      and nucleocapsid (NC) boundary. Identification of Vif variants that were
      efficiently packaged but were unable to modulate Gag processing suggests that Vif
      packaging was necessary but insufficient for the production of 33- and 34-kDa
      processing intermediates. Interestingly, these processing intermediates, like
      Vif, associated with viral nucleoprotein complexes more rigidly than mature
      capsid and NC. We conclude that virus-associated Vif inhibits processing of a
      subset of Gag precursor molecules at the p2/NC primary cleavage site. Modulation
      of processing of a small subset of Gag molecules by physiological levels of Vif
      may be important for virus maturation. However, the accumulation of such
      processing intermediates at high levels of Vif is inhibitory. Thus, rapid
      intracellular degradation of Vif may have evolved as a mechanism to prevent such
      inhibitory effects of Vif.

PMID- 14722069
TI  - Conformational changes in the reaction of pyridoxal kinase.
AB  - To understand the processes involved in the catalytic mechanism of pyridoxal
      kinase (PLK),1 we determined the crystal structures of PLK.AMP-PCP-pyridoxamine,
      PLK.ADP.PLP, and PLK.ADP complexes. Comparisons of these structures have revealed
      that PLK exhibits different conformations during its catalytic process. After the
      binding of AMP-PCP (an analogue that replaced ATP) and pyridoxamine to PLK, this
      enzyme retains a conformation similar to that of the PLK.ATP complex. The
      distance between the reacting groups of the two substrates is 5.8 A apart,
      indicating that the position of ATP is not favorable to spontaneous transfer of
      its phosphate group. However, the structure of PLK.ADP.PLP complex exhibited
      significant changes in both the conformation of the enzyme and the location of
      the ligands at the active site. Therefore, it appears that after binding of both
      substrates, the enzyme-substrate complex requires changes in the protein
      structure to enable the transfer of the phosphate group from ATP to vitamin B(6).
      Furthermore, a conformation of the enzyme-substrate complex before the transition
      state of the enzymatic reaction was also hypothesized.

PMID- 14722070
TI  - Myotubularin regulates the function of the late endosome through the gram domain
      phosphatidylinositol 3,5-bisphosphate interaction.
AB  - Myotubularin and related proteins constitute a large and highly conserved family
      possessing phosphoinositide 3-phosphatase activity, although not all members
      possess this activity. This family contains a conserved region called the GRAM
      domain that is found in a variety of proteins associated with membrane-coupled
      processes and signal transduction. Mutations of myotubularin are found in X
      linked myotubular myopathy, a severe muscle disease. Mutations in the GRAM domain
      are responsible for this condition, suggesting crucial roles for this region.
      Here, we show that the GRAM domain of myotubularin binds to phosphoinositide with
      the highest affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P(2)).
      In patients with myotubular myopathy, mutations in the myotubularin GRAM domain
      eliminate this binding, indicating that the PtdIns(3,5)P(2) binding ability of
      the GRAM (glucosyltransferases, Rablike GTPase activators and myotubularin)
      domain is crucial for the functions of myotubularin in vivo. Stimulation of
      epidermal growth factor recruits myotubularin to the late endosomal compartment
      in a manner dependent on the phosphoinositide binding. Overexpression of
      myotubularin inhibits epidermal growth factor receptor trafficking from late
      endosome to lysosome and induces the large endosomal vacuoles. Thus, our data
      suggest that myotubularin phosphatase physiologically functions in late endosomal
      trafficking and vacuolar morphology through interaction with PtdIns(3,5)P(2).

PMID- 14722071
TI  - Calcium current in rat cardiomyocytes is modulated by the carboxyl-terminal ahnak
      domain.
AB  - Ahnak, a protein of 5643 amino acids, interacts with the regulatory beta-subunit
      of cardiac calcium channels and with F-actin. Recently, we defined the binding
      sites among the protein partners in the carboxyl-terminal domain of ahnak. Here
      we further narrowed down the beta(2)-interaction sites to the carboxyl-terminal
      188 amino acids of ahnak by the recombinant ahnak protein fragments P3 (amino
      acids 5456-5556) and P4 (amino acids 5556-5643). The effects of these P3 and P4
      fragments on the calcium current were investigated under whole-cell patch clamp
      conditions on rat ventricular cardiomyocytes. P4 but not P3 increased
      significantly the current amplitude by 22.7 +/- 5% without affecting its voltage
      dependence. The slow component of calcium current inactivation was slowed down by
      both P3 and P4, whereas only P3 slowed significantly the fast one. The composite
      recombinant protein fragment P3-P4 induced similar modifications to the ones
      induced by each of the ahnak fragments. In the presence of carboxyl-terminal
      ahnak protein fragments, isoprenaline induced a similar relative increase in
      current amplitude and shift in current kinetics. The actin-stabilizing agents,
      phalloidin and jasplakinolide, did not modify the effects of these ahnak protein
      fragments on calcium current in control conditions nor in the presence of
      isoprenaline. Hence, our results suggest that the functional effects of P3, P4,
      and P3-P4 on calcium current are mediated by targeting the ahnak-beta(2)-subunit
      interaction rather than by targeting the ahnak-F-actin interaction. More
      specifically they suggest that binding of the beta(2)-subunit to the endogenous
      subsarcolemmal giant ahnak protein re-primes the alpha(1C)/beta(2)-subunit
      interaction and that the ahnak-derived proteins relieve the beta(2)-subunit from
      this inhibition.

PMID- 14722072
TI  - Structure and DNA-binding sites of the SWI1 AT-rich interaction domain (ARID)
      suggest determinants for sequence-specific DNA recognition.
AB  - ARID (AT-rich interaction domain) is a homologous family of DNA-binding domains
      that occur in DNA-binding proteins from a wide variety of species, ranging from
      yeast to nematodes, insects, mammals, and plants. SWI1, a member of the SWI/SNF
      protein complex that is involved in chromatin remodeling during transcription,
      contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does
      not select for a specific DNA sequence from a random sequence pool. The lack of
      sequence specificity shown by the SWI1 ARID domain stands in contrast to the
      other characterized ARID domains, which recognize specific AT-rich sequences. We
      have solved the three-dimensional structure of human SWI1 ARID using solution NMR
      methods. In addition, we have characterized nonspecific DNA binding by the SWI1
      ARID domain. Results from this study indicate that a flexible, long, internal
      loop in the ARID motif is likely to be important for sequence-specific DNA
      recognition. The structure of the human SWI1 ARID domain also represents a
      distinct structural subfamily. Studies of ARID indicate that the boundary of DNA
      binding structural and functional domains can extend beyond the sequence
      homologous region in a homologous family of proteins. Structural studies of
      homologous domains such as the ARID family of DNA-binding domains should provide
      information to better predict the boundary of structural and functional domains
      in structural genomic studies.

PMID- 14722073
TI  - Recruitment of distinct chromatin-modifying complexes by tamoxifen-complexed
      estrogen receptor at natural target gene promoters in vivo.
AB  - Tamoxifen, a breast cancer therapeutic, is a tissue-selective estrogen receptor
      modulator (SERM), which acts as an antiestrogen in the mammary tissue and
      displays estrogenic activity in other tissues such as bone and uterus. In order
      to understand the mechanisms underlying the antiestrogenic effect of this
      prototype SERM, we performed an analysis of the cofactors that interact with ER
      complexed with 4-hydroxytamoxifen (OHT) at natural target genes in a human breast
      tumor cell line MCF-7. Employing chromatin immunoprecipitation (ChIP), we
      observed that treatment with OHT rapidly induces the binding of ERalpha to the E
      responsive promoter regions of pS2 and c-myc genes. Promoter-bound OHT-complexed
      ERa coordinately recruited the components of a multiprotein complex containing
      the corepressor NCoR, histone deacetylase 3 (HDAC3), and a WD40-repeat protein
      TBL1. Surprisingly, the OHT-complexed ERalpha also recruited a chromatin
      remodeling NuRD complex in which histone deacetylase 1 (HDAC1) is associated with
      several polypeptides including metastasis-associated protein 1/2 (MTA1/2), and
      SWI2/SNF2-related ATPase Mi2. Kinetic studies revealed that following OHT
      addition the recruitment of these HDAC complexes to pS2 or the c-myc promoter
      occurs in a sequential manner; the NCoR-HDAC3 complex is recruited earlier than
      the NuRD complex. Serial ChIP experiments indicated that the ER-NCoR-HDAC3 and ER
      NuRD complexes are distinct, and they do not occupy the target gene promoter
      simultaneously. We also established a close temporal link between the appearance
      of the HDAC complexes at the E-responsive regions of pS2 and c-myc promoters,
      local hypoacetylation of specific lysine residues in N-terminal tails of histones
      H3 and H4, and disappearance of RNA polymerase II from the target gene loci.
      Collectively, our studies indicated that transcriptional repression by tamoxifen
      bound ER at E-regulated gene promoters involves a dynamic interplay of multiple
      distinct chromatin-modifying/remodeling complexes.

PMID- 14722074
TI  - Ca2+ and phosphatidylinositol 4,5-bisphosphate stabilize a Gbeta gamma-sensitive
      state of Ca V2 Ca 2+ channels.
AB  - Direct interactions between G-protein betagamma subunits and N- or P/Q-type
      Ca(2+) channels mediate the inhibitory action of several neurotransmitters in the
      brain. Membrane potential, channel phosphorylation, or auxiliary subunit
      association tightly regulate these interactions and the consequent inhibition of
      Ca(2+) current. We now provide evidence that intracellular Ca(2+) concentration
      and phosphoinositides play a stabilizing role in this direct voltage-dependent
      inhibition. Lowering resting cytosolic Ca(2+) concentration in Xenopus oocytes
      expressing Ca(V)2Ca(2+) channels strongly decreased basal as well as phasic,
      agonist-dependent inhibition of Ca(2+) channels by G-proteins. Decreasing
      phosphoinositide levels also suppressed G-protein inhibition and completely
      occluded the effects of a subsequent injection of Ca(2+) chelator. Similar
      regulations are observed in mouse dorsal root ganglia neurons. Alteration of G
      protein block by these agents is independent of protein phosphorylation,
      cytoskeleton dynamics, and GTPase or GDP/GTP exchange activity, suggesting a
      direct action at the level of the Ca(2+) channel/Gbetagamma-protein interaction.
      Moreover, affinity binding experiments of intracellular loops of the Ca(V)2.1
      Ca(2+) channels to different phospholipids revealed specific interactions between
      the C-terminal tail of the channel and phosphoinositides. Taken together these
      data indicate that a Ca(2+)-sensitive interaction of the C-terminal tail of P/Q
      channels with the plasma membrane is important for G-protein regulation.

PMID- 14722075
TI  - Crystal structure of the human RORalpha Ligand binding domain in complex with
      cholesterol sulfate at 2.2 A.
AB  - The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of
      the subfamily 1 of nuclear hormone receptors. Our recent structural and
      functional studies have led to the hypothesis that cholesterol or a cholesterol
      derivative is the natural ligand of RORalpha. We have now solved the x-ray
      crystal structure of the ligand binding domain of RORalpha in complex with
      cholesterol-3-O-sulfate following a ligand exchange experiment. In contrast to
      the 3-hydroxyl of cholesterol, the 3-O-sulfate group makes additional direct
      hydrogen bonds with three residues of the RORalpha ligand binding domain, namely
      NH-Gln(289), NH-Tyr(290), and NH1-Arg(370). When compared with the complex with
      cholesterol, seven well ordered water molecules have been displaced, and the
      ligand is slightly shifted toward the hydrophilic part of the ligand binding
      pocket, which is ideally suited for interactions with a sulfate group. These
      additional ligand-protein interactions result in an increased affinity of
      cholesterol sulfate when compared with cholesterol, as shown by mass spectrometry
      analysis done under native conditions and differential scanning calorimetry.
      Moreover, mutational studies show that the higher binding affinity of cholesterol
      sulfate translates into an increased transcriptional activity of RORalpha. Our
      findings suggest that cholesterol sulfate could play a crucial role in the
      regulation of RORalpha in vivo.

PMID- 14722076
TI  - Alternative splicing in the aggrecan G3 domain influences binding interactions
      with tenascin-C and other extracellular matrix proteins.
AB  - The proteoglycans aggrecan, versican, neurocan, and brevican bind hyaluronan
      through their N-terminal G1 domains, and other extracellular matrix proteins
      through the C-type lectin repeat in their C-terminal G3 domains. Here we identify
      tenascin-C as a ligand for the lectins of all these proteoglycans and map the
      binding site on the tenascin molecule to fibronectin type III repeats, which
      corresponds to the proteoglycan lectin-binding site on tenascin-R. In the G3
      domain, the C-type lectin is flanked by epidermal growth factor (EGF) repeats and
      a complement regulatory protein-like motif. In aggrecan, these are subject to
      alternative splicing. To investigate if these flanking modules affect the C-type
      lectin ligand interactions, we produced recombinant proteins corresponding to
      aggrecan G3 splice variants. The G3 variant proteins containing the C-type lectin
      showed different affinities for various ligands, including tenascin-C, tenascin
      R, fibulin-1, and fibulin-2. The presence of an EGF motif enhanced the affinity
      of interaction, and in particular the splice variant containing both EGF motifs
      had significantly higher affinity for ligands, such as tenascin-R and fibulin-2.
      The mRNA for this splice variant was shown by reverse transcriptase-PCR to be
      expressed in human chondrocytes. Our findings suggest that alternative splicing
      in the aggrecan G3 domain may be a mechanism for modulating interactions and
      extracellular matrix assembly.

PMID- 14722077
TI  - Functional analysis of the interface regions involved in interactions between the
      central cytoplasmic loop and the C-terminal tail of adenylyl cyclase.
AB  - The mammalian adenylyl cyclase is a membrane-bound enzyme that is predicted to
      have 12 trans-membrane spans. Between membrane spans 6 and 7 there is a large
      cytoplasmic loop, which, along with the C-terminal tail, makes up the catalytic
      site of the enzyme. Crystal structures of these soluble cytoplasmic domains have
      identified the regions that are involved in interactions with each other. The
      functional consequences of these interactions in the full-length membrane
      embedded enzymes have not been established. In this study, we analyzed the role
      of various interaction regions within the central cytoplasmic loop (C1) and the C
      terminal tail (C2) on basal, Galphas-, forskolin-, and Mn(2+)-stimulated
      activities of adenylyl cyclases 2 and 6 (AC2 and AC6). We tested synthetic
      peptides encoding the different interface surfaces of both the C1 and C2 domain
      on different activities of membrane-bound AC2 and AC6 expressed in insect cells.
      We found the C1-alpha2-beta2-beta3 and C2-beta2'-beta3' regions to be involved in
      stimulation by Galphas and forskolin but not in the basal or Mn(2+)-stimulated
      activities. Both the C1-beta4-beta5-alpha4 region and the C2-alpha3'-beta4'
      region play a role in the Galphas- and forskolin-stimulated activities as well as
      in basal activity, because the peptides encoding these regions inhibit basal
      activity by 30%. In contrast, the C2-alpha2' region peptide inhibits both basal
      and Mn(2+)-stimulated activity by >50%. These results suggest that the different
      stimulated activities may involve distinct interface interactions in the intact
      enzyme and, consequently, the distinct mechanisms by which Mn(2+) activates the
      enzyme as compared with Galphas and forskolin, leading to the possibility that
      the full-length adenylyl cyclase may have multiple catalytically competent
      configurations.

PMID- 14722078
TI  - Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal
      hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common
      neurodegenerative diseases that occur either in relatively rare, familial forms
      or in common, sporadic forms. The genetic defects underlying several monogenic
      familial forms of AD and PD have recently been identified, however, the causes of
      other AD and PD cases, particularly sporadic cases, remain unclear. To gain
      insights into the pathogenic mechanisms involved in AD and PD, we used a
      proteomic approach to identify proteins with altered expression levels and/or
      oxidative modifications in idiopathic AD and PD brains. Here, we report that the
      protein level of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), a neuronal de
      ubiquitinating enzyme whose mutation has been linked to an early-onset familial
      PD, is down-regulated in idiopathic PD as well as AD brains. By using a
      combination of two-dimensional gel electrophoresis and mass spectrometry, we have
      identified three human brain UCH-L1 isoforms, a full-length form and two amino
      terminally truncated forms. Our proteomic analyses reveal that the full-length
      UCH-L1 is a major target of oxidative damage in AD and PD brains, which is
      extensively modified by carbonyl formation, methionine oxidation, and cysteine
      oxidation. Furthermore, immunohistochemical studies show that prominent UCH-L1
      immunostaining is associated with neurofibrillary tangles and that the level of
      soluble UCH-L1 protein is inversely proportional to the number of tangles in AD
      brains. Together, these results provide evidence supporting a direct link between
      oxidative damage to the neuronal ubiquitination/de-ubiquitination machinery and
      the pathogenesis of sporadic AD and PD.

PMID- 14722079
TI  - Crystal structure of the calcium-stabilized human factor IX Gla domain bound to a
      conformation-specific anti-factor IX antibody.
AB  - The binding of Factor IX to membranes during blood coagulation is mediated by the
      N-terminal gamma-carboxyglutamic acid-rich (Gla) domain, a membrane-anchoring
      domain found on vitamin K-dependent blood coagulation and regulatory proteins.
      Conformation-specific anti-Factor IX antibodies are directed at the calcium
      stabilized Gla domain and interfere with Factor IX-membrane interaction. One such
      antibody, 10C12, recognizes the calcium-stabilized form of the Gla domain of
      Factor IX. We prepared the fully carboxylated Gla domain of Factor IX by solid
      phase peptide synthesis and crystallized Factor IX-(1-47) in complex with Fab
      fragments of the 10C12 antibody. The overall structure of the Gla domain in the
      Factor IX-(1-47)-antibody complex at 2.2 A is similar to the structure of the
      Factor IX Gla domain in the presence of calcium ions as determined by NMR
      spectroscopy (Freedman, S. J., Furie, B. C., Furie, B., and Baleja, J. D. (1995)
      Biochemistry 34, 12126-12137) and by x-ray crystallography (Shikamoto, Y.,
      Morita, T., Fujimoto, Z., and Mizuno, H. (2003) J. Biol. Chem. 278, 24090-24094).
      The complex structure shows that the complementarity determining region loops of
      the 10C12 antibody form a hydrophobic pocket to accommodate the hydrophobic patch
      of the Gla domain consisting of Leu-6, Phe-9, and Val-10. Polar interactions also
      play an important role in the antibody-antigen recognition. Furthermore, the
      calcium coordination network of the Factor IX Gla domain is different than in Gla
      domain structures of other vitamin K-dependent proteins. We conclude that this
      antibody is directed at the membrane binding site in the omega loop of Factor IX
      and blocks Factor IX function by inhibiting its interaction with membranes.

PMID- 14722080
TI  - Inositol 1,4,5-trisphosphate receptor localization and stability in neonatal
      cardiomyocytes requires interaction with ankyrin-B.
AB  - The molecular mechanisms required for inositol 1,4,5-trisphosphate receptor
      (InsP(3)R) targeting to specialized endoplasmic reticulum membrane domains are
      unknown. We report here a direct, high affinity interaction between InsP(3)R and
      ankyrin-B and demonstrate that this association is critical for InsP(3)R post
      translational stability and localization in cultures of neonatal cardiomyocytes.
      Recombinant ankyrin-B membrane-binding domain directly interacts with purified
      cerebellar InsP(3)R (K(d) = 2 nm). 220-kDa ankyrin-B co-immunoprecipitates with
      InsP(3)R in tissue extracts from brain, heart, and lung. Alanine-scanning
      mutagenesis of the ankyrin-B ANK (ankyrin repeat) repeat beta-hairpin loop tips
      revealed that consecutive ANK repeat beta-hairpin loop tips (repeats 22-24) are
      required for InsP(3)R interaction, thus providing the first detailed evidence of
      how ankyrin polypeptides associate with membrane proteins. Pulse-chase
      biosynthesis experiments demonstrate that reduction or loss of ankyrin-B in
      ankyrin-B (+/-) or ankyrin-B (-/-) neonatal cardiomyocytes leads to approximately
      3-fold reduction in half-life of newly synthesized InsP(3)R. Furthermore,
      interactions with ankyrin-B are required for InsP(3)R stability as abnormal
      InsP(3)R phenotypes, including mis-localization, and reduced half-life in ankyrin
      B (+/-) cardiomyocytes can be rescued by green fluorescent protein (GFP)-220-kDa
      ankyrin-B but not by GFP-220-kDa ankyrin-B mutants, which do not associate with
      InsP(3)R. These new results provide the first physiological evidence of a
      molecular partner required for early post-translational stability of InsP(3)R.

PMID- 14722081
TI  - Bipartite 3'-cis-acting signal for replication in yeast 23 S RNA virus and its
      repair.
AB  - 23 S RNA narnavirus is a persistent positive strand RNA virus found in
      Saccharomyces cerevisiae. The viral genome is small (2.9 kb) and only encodes its
      RNA-dependent RNA polymerase. Recently, we have succeeded in generating 23 S RNA
      virus from an expression vector containing the entire viral cDNA sequence. Using
      this in vivo launching system, we analyzed the 3'-cis-acting signals for
      replication. The 3'-non-coding region of 23 S RNA contains two cis-elements. One
      is a stretch of 4 Cs at the 3' end, and the other is a mismatched pair in a stem
      loop structure that partially overlaps the terminal 4 Cs. In the latter element,
      the loop or stem sequence is not important but the stem structure with the
      mismatch pair is essential. The mismatched bases should be purines. Any
      combination of purines at the mismatch pair bestowed capability of replication on
      the RNA, whereas converting it to a single bulge at either side of the stem
      abolished the activity. The terminal and penultimate Cs at the 3' end could be
      eliminated or modified to other nucleotides in the launching plasmid without
      affecting virus generation. However, the viruses generated regained or restored
      these Cs at the 3' terminus. Considering the importance of the viral 3' ends in
      RNA replication, these results suggest that this 3' end repair may contribute to
      the persistence of 23 S RNA virus in yeast by maintaining the genomic RNA termini
      intact. We discuss possible mechanisms for this 3' end repair in vivo.

PMID- 14722082
TI  - Fungal ammonia fermentation, a novel metabolic mechanism that couples the
      dissimilatory and assimilatory pathways of both nitrate and ethanol. Role of
      acetyl CoA synthetase in anaerobic ATP synthesis.
AB  - Fungal ammonia fermentation is a novel dissimilatory metabolic mechanism that
      supplies energy under anoxic conditions. The fungus Fusarium oxysporum reduces
      nitrate to ammonium and simultaneously oxidizes ethanol to acetate to generate
      ATP (Zhou, Z., Takaya, N., Nakamura, A., Yamaguchi, M., Takeo, K., and Shoun, H.
      (2002) J. Biol. Chem. 277, 1892-1896). We identified the Aspergillus nidulans
      genes involved in ammonia fermentation by analyzing fungal mutants. The results
      showed that assimilatory nitrate and nitrite reductases (the gene products of
      niaD and niiA) were essential for reducing nitrate and for anaerobic cell growth
      during ammonia fermentation. We also found that ethanol oxidation is coupled with
      nitrate reduction and catalyzed by alcohol dehydrogenase, coenzyme A (CoA)
      acylating aldehyde dehydrogenase, and acetyl-CoA synthetase (Acs). This is
      similar to the mechanism suggested in F. oxysporum except A. nidulans uses Acs to
      produce ATP instead of the ADP-dependent acetate kinase of F. oxysporum. The
      production of Acs requires a functional facA gene that encodes Acs and that is
      involved in ethanol assimilation and other metabolic processes. We purified the
      gene product of facA (FacA) from the fungus to show that the fungus acetylates
      FacA on its lysine residue(s) specifically under conditions of ammonia
      fermentation to regulate its substrate affinity. Acetylated FacA had higher
      affinity for acetyl-CoA than for acetate, whereas non-acetylated FacA had more
      affinity for acetate. Thus, the acetylated variant of the FacA protein is
      responsible for ATP synthesis during fungal ammonia fermentation. These results
      showed that the fungus ferments ammonium via coupled dissimilatory and
      assimilatory mechanisms.

PMID- 14722083
TI  - Comparative analyses of the three-dimensional structures and enzymatic properties
      of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein
      kinase II.
AB  - Ca(2+)-calmodulin-dependent protein kinase II (CaM-kinase II) is a ubiquitous
      Ser/Thr-directed protein kinase that is expressed from a family of four genes
      (alpha, beta, gamma, and delta) in mammalian cells. We have documented the three
      dimensional structures and the biophysical and enzymatic properties of the four
      gene products. Biophysical analyses showed that each isoform assembles into
      oligomeric forms and their three-dimensional structures at 21-25 A revealed that
      all four isoforms were dodecamers with similar but highly unusual architecture. A
      gear-shaped core comprising the association domain has the catalytic domains
      tethered on appendages, six of which extend from both ends of the core. At this
      level of resolution, we can discern no isoform-dependent differences in
      ultrastructure of the holoenzymes. Enzymatic analyses showed that the isoforms
      were similar in their K(m) for ATP and the peptide substrate syntide, but showed
      significant differences in their interactions with Ca(2+)-calmodulin as assessed
      by binding, substrate phosphorylation, and autophosphorylation. Interestingly,
      the rank order of CaM binding affinity (gamma > beta > delta > alpha) does not
      directly correlate with the rank order of their CaM dependence for
      autophosphorylation (beta > gamma > delta > alpha). Simulations utilizing this
      data revealed that the measured differences in CaM binding affinities play a
      minor role in the autophosphorylation of the enzyme, which is largely dictated by
      the rate of autophosphorylation for each isoform.

PMID- 14722084
TI  - Development and characterization of a conditional mitochondrial complex I
      assembly system.
AB  - We developed a conditional complex I assembly system in a Chinese hamster
      fibroblast mutant line, CCL16-B2, that does not express the NDUFA1 gene (encoding
      the MWFE protein). In this mutant, a hemagglutinin (HA) epitope-tagged MWFE
      protein was expressed from a doxycycline-inducible promoter. The expression of
      the protein was absolutely dependent on the presence of doxycycline, and the gene
      could be turned off completely by removal of doxycycline. These experiments
      demonstrated a key role of MWFE in the pathway of complex I assembly. Upon
      induction the MWFE.HA protein reached steady-state levels within 24 h, but the
      appearance of fully active complex I was delayed by another approximately 24 h.
      The MWFE appeared in a precomplex that probably includes one or more subunits
      encoded by mtDNA. The fate of MWFE and the stability of complex I were themselves
      very tightly linked to the activity of mitochondrial protein synthesis and to the
      assembly of subunits encoded by mtDNA (ND1-6 and ND4L). This novel conditional
      system can shed light not only on the mechanism of complex I assembly but
      emphasizes the role of subunits previously thought of as "accessory." It promises
      to have broader applications in the study of cellular energy metabolism and
      production of reactive oxygen species and related processes.

PMID- 14722085
TI  - RanBPM is a phosphoprotein that associates with the plasma membrane and interacts
      with the integrin LFA-1.
AB  - Integrin adhesion receptors can act as signaling receptors that transmit
      information from the extracellular environment to the interior of the cell,
      affecting many fundamental cellular processes, such as cell motility,
      proliferation, differentiation, and survival. Integrin signaling depends on the
      formation of organized sub-membrane complexes that comprise cytoskeletal,
      adapter, and signaling molecules. The identification of molecules that interact
      with the cytoplasmic domain of integrins has been the focus of research aimed to
      elucidating the mechanistic basis of integrin signal transduction. We have
      identified RanBPM as a novel interactor of the beta(2) integrin LFA-1 in a yeast
      two-hybrid screen. In the same assay, RanBPM also interacted with the beta(1)
      integrin cytoplasmic domain. We demonstrate that RanBPM is a peripheral membrane
      protein and that integrins and RanBPM interact in vitro and in vivo and co
      localize at the cell membrane. We find that RanBPM is phosphorylated on serine
      residues; phosphorylation of RanBPM is increased by stress stimuli and decreased
      by treatment with the p38 kinase inhibitor SB203580. Transfection of RanBPM
      synergizes with LFA-1-mediated adhesion in the transcriptional activation of an
      AP-1-dependent promoter, indicating that the two proteins interact functionally
      as well. We suggest that RanBPM may constitute a molecular scaffold that
      contributes to coupling LFA-1 and other integrins with intracellular signaling
      pathways.

PMID- 14722086
TI  - Alpha1-syntrophin modulates turnover of ABCA1.
AB  - ABCA1 (ATP-binding cassette transporter A1) mediates the release of cellular
      cholesterol and phospholipid to form high density lipoprotein. Functions of ABCA1
      are highly regulated at the transcriptional and post-transcriptional levels, and
      the synthesized ABCA1 protein turns over rapidly with a half-life of 1-2 h. To
      examine whether the functions of ABCA1 are modulated by associated proteins, a
      yeast two-hybrid library was screened with the C-terminal 120 amino acids of
      ABCA1. Two PDZ (PSD95-Discs large-ZO1) proteins, alpha1-syntrophin and Lin7, were
      found to interact with ABCA1. Immunoprecipitation revealed that alpha1-syntrophin
      interacted with ABCA1 strongly and that the interaction was via the C-terminal
      three amino acids SYV of ABCA1. Co-expression of alpha1-syntrophin in human
      embryonic kidney 293 cells retarded degradation of ABCA1 and made the half-life
      of ABCA1 five times longer than in the cells not expressing alpha1-syntrophin.
      This effect is not common among PDZ-containing proteins interacting with ABCA1,
      because Lin7, which was also found to interact with the C terminus region of
      ABCA1, did not have a significant effect on the half-life of ABCA1. Co-expression
      of alpha1-syntrophin significantly increased the apoA-I-mediated release of
      cholesterol. ABCA1 was co-immunoprecipitated with alpha1-syntrophin from mouse
      brain. These results suggest that alpha1-syntrophin is involved in intracellular
      signaling, which determines the stability of ABCA1 and modulates cellular
      cholesterol release.

PMID- 14722087
TI  - S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates
      osteopontin transcription in endotoxin-stimulated murine macrophages.
AB  - Osteopontin (OPN) is a highly hydrophilic and negatively charged sialoprotein of
      approximately 298 amino acids that contains a Gly-Arg-Gly-Asp-Ser sequence. It is
      a secreted protein with diverse regulatory functions, including cell adhesion and
      migration, tumor growth and metastasis, atherosclerosis, aortic valve
      calcification, and repair of myocardial injury. Despite the many recognized
      functions of OPN, very little is known of the transcriptional regulation of OPN.
      In this regard, we have previously demonstrated that OPN transcription and
      promoter activity are significantly up-regulated in response to NO in a system of
      endotoxin-stimulated murine macrophages. However, the specific cis- and trans
      regulatory elements that determine the extent of endotoxin- and NO-mediated
      induction of OPN synthesis are unknown. In this follow-up study, we demonstrate
      that: 1) OPN gene transcription is regulated by a constitutive transcriptional
      repressor protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B); 2)
      inhibition of in vivo hnRNP DNA binding activity is accompanied by increased S
      nitrosylation of hnRNP A/B in the setting of lipopolysaccharide (LPS)-mediated NO
      synthesis; 3) inhibition of LPS mediated NO synthesis restores hnRNP DNA binding
      and decreases the extent of S-nitrosylation; and 4) S-nitrosylation of hnRNP at
      cysteine 104 inhibits in vitro DNA binding activity, which is reversed by
      dithiothreitol. Our findings suggest that LPS induced S-nitrosylation of hnRNP
      inhibits its activity as a constitutive repressor of the OPN promoter and results
      in enhanced OPN expression.

PMID- 14722088
TI  - The zinc finger protein Zat12 is required for cytosolic ascorbate peroxidase 1
      expression during oxidative stress in Arabidopsis.
AB  - Cytosolic ascorbate peroxidase 1 (Apx1) is a key H(2)O(2) removal enzyme in
      plants. Microarray analysis of Apx1-deficient Arabidopsis plants revealed that
      the expression of two zinc finger proteins (Zat12 and Zat7) and a WRKY
      transcription factor (WRKY25) is elevated in knock-out Apx1 plants grown under
      controlled conditions. Because mutants lacking Apx1 accumulate H(2)O(2), we
      examined the correlation between H(2)O(2) and the expression of Zat12, Zat7,
      WRKY25, and Apx1. The expression of Zat12, Zat7, and WRKY25 was simultaneously
      elevated in cells in response to oxidative stress (i.e. H(2)O(2) or paraquat
      application), heat shock, or wounding. In contrast, light or osmotic stress did
      not enhance the expression of these putative transcription factors. All stresses
      tested enhanced the expression of Apx1. Transgenic plants expressing Zat12 or
      Zat7 could tolerate oxidative stress. In contrast, transgenic plants expressing
      WRKY25 could not. Although the expression of Zat12, Zat7, or WRKY25 in transgenic
      plants did not enhance the expression of Apx1 under controlled conditions, Zat12
      deficient plants were unable to enhance the expression of Apx1, Zat7, or WRKY25
      in response to H(2)O(2) or paraquat application. Zat12-deficient plants were also
      more sensitive than wild type plants to H(2)O(2) application as revealed by a
      higher level of H(2)O(2)-induced protein oxidation detected in these plants by
      protein blots. Our results suggest that Zat12 is an important component of the
      oxidative stress response signal transduction network of Arabidopsis required for
      Zat7, WRKY25, and Apx1 expression during oxidative stress.

PMID- 14722089
TI  - Roles of the proline-rich domain in SLP-76 subcellular localization and T cell
      function.
AB  - The adaptor protein Src homology (SH)2 domain-containing and leukocyte-specific
      phosphoprotein of 76 kDa (SLP-76) is critical for signal transduction in multiple
      hematopoietic lineages. It links proximal and distal T cell receptor signaling
      events through its function as a molecular scaffold in the assembly of
      multimolecular signaling complexes. Here we studied the functional roles of sub
      domains within the SLP-76 proline-rich region, specifically the Gads binding
      domain and the recently defined P1 domain. To gain a further understanding of the
      functions mediated by this region, we used three complementary approaches as
      follows: reconstitution of SLP-76-deficient cells with functional domain deletion
      mutants, blocking molecular associations through the expression of a dominant
      negative protein fragment, and directed localization of SLP-76 to assess the role
      of the domains in SLP-76 recruitment. We find the Gads binding domain and the P1
      domain are both necessary for optimal SLP-76 function, and in the absence of
      these two regions, SLP-76 is functionally inert. Furthermore, we provide direct
      evidence that SLP-76 localization and, in turn, function are dependent upon
      association with Gads.

PMID- 14722090
TI  - In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the
      defense against Gram-positive bacterial infection in Drosophila adults.
AB  - The Drosophila immune system discriminates between different classes of
      infectious microbes and responds with pathogen-specific defense reactions via the
      selective activation of the Toll and the immune deficiency (Imd) signaling
      pathways. The Toll pathway mediates most defenses against Gram-positive bacteria
      and fungi, whereas the Imd pathway is required to resist Gram-negative bacterial
      infection. Microbial recognition is achieved through peptidoglycan recognition
      proteins (PGRPs); Gram-positive bacteria activate the Toll pathway through a
      circulating PGRP (PGRP-SA), and Gram-negative bacteria activate the Imd pathway
      via PGRP-LC, a putative transmembrane receptor, and PGRP-LE. Gram-negative
      binding proteins (GNBPs) were originally identified in Bombyx mori for their
      capacity to bind various microbial compounds. Three GNBPs and two related
      proteins are encoded in the Drosophila genome, but their function is not known.
      Using inducible expression of GNBP1 double-stranded RNA, we now demonstrate that
      GNBP1 is required for Toll activation in response to Gram-positive bacterial
      infection; GNBP1 double-stranded RNA expression renders flies susceptible to Gram
      positive bacterial infection and reduces the induction of the antifungal peptide
      encoding gene Drosomycin after infection by Gram-positive bacteria but not after
      fungal infection. This phenotype induced by GNBP1 inactivation is identical to a
      loss-of-function mutation in PGRP-SA, and our genetic studies suggest that GNBP1
      acts upstream of the Toll ligand Spatzle. Altogether, our results demonstrate
      that the detection of Gram-positive bacteria in Drosophila requires two putative
      pattern recognition receptors, PGRP-SA and GNBP1.

PMID- 14722091
TI  - Fission yeast homolog of neuronal calcium sensor-1 (Ncs1p) regulates sporulation
      and confers calcium tolerance.
AB  - The neuronal calcium sensor (NCS) proteins (e.g. recoverin, neurocalcins, and
      frequenin) are expressed at highest levels in excitable cells, and some of them
      regulate desensitization of G protein-coupled receptors. Here we present NMR
      analysis and genetic functional studies of an NCS homolog in fission yeast
      (Ncs1p). Ncs1p binds three Ca2+ ions at saturation with an apparent affinity of 2
      microm and Hill coefficient of 1.9. Analysis of NMR and fluorescence spectra of
      Ncs1p revealed significant Ca2+-induced protein conformational changes indicative
      of a Ca2+-myristoyl switch. The amino-terminal myristoyl group is sequestered
      inside a hydrophobic cavity of the Ca2+-free protein and becomes solvent-exposed
      in the Ca2+-bound protein. Subcellular fractionation experiments showed that
      myristoylation and Ca2+ binding by Ncs1p are essential for its translocation from
      cytoplasm to membranes. The ncs1 deletion mutant (ncs1Delta) showed two distinct
      phenotypes: nutrition-insensitive sexual development and a growth defect at high
      levels of extracellular Ca2+ (0.1 m CaCl(2)). Analysis of Ncs1p mutants lacking
      myristoylation (Ncs1p(G2A)) or deficient in Ca2+ binding
      (Ncs1p(E84Q/E120Q/E168Q)) revealed that Ca2+ binding was essential for both
      phenotypes, while myristoylation was less critical. Exogenous cAMP, a key
      regulator for sexual development, suppressed conjugation and sporulation of
      ncs1Delta, suggesting involvement of Ncs1p in the adenylate cyclase pathway
      turned on by the glucose-sensing G protein-coupled receptor Git3p. Starvation
      independent sexual development of ncs1Delta was also complemented by retinal
      recoverin, which controls Ca2+-regulated desensitization of rhodopsin. In
      contrast, the Ca2+-intolerance of ncs1Delta was not affected by cAMP or
      recoverin, suggesting that the two ncs1Delta phenotypes are mechanistically
      independent. We propose that Schizosaccharomyces pombe Ncs1p negatively regulates
      sporulation perhaps by controlling Ca2+-dependent desensitization of Git3p.

PMID- 14722092
TI  - A Conserved alpha-helical motif mediates the binding of diverse nuclear proteins
      to the SRC1 interaction domain of CBP.
AB  - CREB-binding protein (CBP) and p300 contain modular domains that mediate protein
      protein interactions with a wide variety of nuclear factors. A C-terminal domain
      of CBP (referred to as the SID) is responsible for interaction with the alpha
      helical AD1 domain of p160 coactivators such as the steroid receptor coactivator
      (SRC1), and also other transcriptional regulators such as E1A, Ets-2, IRF3, and
      p53. Here we show that the pointed (PNT) domain of Ets-2 mediates its interaction
      with the CBP SID, and describe the effects of mutations in the SID on binding of
      Ets-2, E1A, and SRC1. In vitro binding studies indicate that SRC1, Ets-2 and E1A
      display mutually exclusive binding to the CBP SID. Consistent with this, we
      observed negative cross-talk between ERalpha/SRC1, Ets-2, and E1A proteins in
      reporter assays in transiently transfected cells. Transcriptional inhibition of
      Ets-2 or GAL4-AD1 activity by E1A was rescued by co-transfection with a CBP
      expression plasmid, consistent with the hypothesis that the observed inhibition
      was due to competition for CBP in vivo. Sequence comparisons revealed that SID
      binding proteins contain a leucine-rich motif similar to the alpha-helix Aalpha1
      of the SRC1 AD1 domain. Deletion mutants of E1A and Ets-2 lacking the conserved
      motif were unable to bind the CBP SID. Moreover, a peptide corresponding to this
      sequence competed the binding of full-length SRC1, Ets-2, and E1A proteins to the
      CBP SID. Thus, a leucine-rich amphipathic alpha-helix mediates mutually exclusive
      interactions of functionally diverse nuclear proteins with CBP.

PMID- 14722093
TI  - Analysis of the regulation of the molecular chaperone Hsp26 by temperature
      induced dissociation: the N-terminal domail is important for oligomer assembly
      and the binding of unfolding proteins.
AB  - Small heat shock proteins (sHsps) are molecular chaperones that efficiently bind
      non-native proteins. All members of this family investigated so far are
      oligomeric complexes. For Hsp26, an sHsp from the cytosol of Saccharomyces
      cerevisiae, it has been shown that at elevated temperatures the 24-subunit
      complex dissociates into dimers. This dissociation seems to be required for the
      efficient interaction with unfolding proteins that results in the formation of
      large, regular complexes comprising Hsp26 and the non-native proteins. To gain
      insight into the molecular mechanism of this chaperone, we analyzed the dynamics
      and stability of the two oligomeric forms of Hsp 26 (i.e. the 24-mer and the
      dimer) in comparison to a construct lacking the N-terminal domain (Hsp26DeltaN).
      Furthermore, we determined the stabilities of complexes between Hsp26 and non
      native proteins. We show that the temperature-induced dissociation of Hsp26 into
      dimers is a completely reversible process that involves only a small change in
      energy. The unfolding of the dissociated Hsp26 dimer or Hsp26DeltaN, which is a
      dimer, requires a much higher energy. Because Hsp26DeltaN was inactive as a
      chaperone, these results imply that the N-terminal domain is of critical
      importance for both the association of Hsp26 with non-native proteins and the
      formation of large oligomeric complexes. Interestingly, complexes of Hsp26 with
      non-native proteins are significantly stabilized against dissociation compared
      with Hsp26 complexes. Taken together, our findings suggest that the quaternary
      structure of Hsp26 is determined by two elements, (i) weak, regulatory
      interactions required to form the shell of 24 subunits and (ii) a strong and
      stable dimerization of the C-terminal domain.

PMID- 14722094
TI  - Capped mRNA with a single nucleotide leader is optimally translated in a
      primitive eukaryote, Giardia lamblia.
AB  - The 5'-untranslated region (5'-UTR) of an mRNA plays an important role in
      translation initiation in eukaryotes. A minimal length of about 20 nucleotides is
      required to prevent leaky ribosome scanning. In one of the most primitive
      eukaryotes, Giardia lamblia, however, the mRNAs have 5'-UTRs mostly in the range
      of 0 to 14 nucleotides without a conserved sequence, which raises the question on
      how the ribosome could effectively scan such short 5'-UTRs for an accurate
      initiation of translation. In the present study, we expressed capped transcripts
      of luciferase gene in Giardia trophozoites via transfection and observed that
      when the 5'-UTR of the transcript was lengthened from 9 to 21 nucleotides, there
      was a corresponding decrease of translation efficiency. Conversely, shortening of
      the 5'-UTR from nine nucleotides down to a single nucleotide did not result in
      any reduced translation or leaky scanning. Translation appeared to initiate
      exclusively from the first initiation codon located downstream from the cap.
      Experimental evidence indicated also that a stem-loop structure immediately
      downstream from the initiation codon exerted significant inhibition on
      translation initiation when the 5'-UTR consisted of less than seven nucleotides.
      This inhibitory effect was abolished by increasing the distance between the stem
      loop and the cap-G structure either upstream or downstream from the start codon,
      thus suggesting a spatial requirement for effective ribosome recruitment.
      Overall, our results suggest an absence of ribosome scanning for AUG in
      initiating translation in Giardia. A capped mRNA with a single nucleotide leader
      is apparently sufficient for recruiting ribosome and initiating translation.

PMID- 14722095
TI  - Thiol modification of cysteine 327 in the eighth transmembrane domain of the
      light subunit xCT of the heteromeric cystine/glutamate antiporter suggests close
      proximity to the substrate binding site/permeation pathway.
AB  - We measured sensitivity to thiol modification of the heteromeric
      glutamate/cystine transporter 4F2hc-xCT expressed in Xenopus oocytes. p
      Chloromercuribenzoate (pCMB) and p-chloromercuribenzenesulfonate (pCMBS) rapidly
      blocked transport activity. Cys(327), located in the middle of the eighth
      transmembrane domain of the light subunit (xCT), was found to be the main target
      of inactivation. Cysteine, an impermeant reducing reagent, reversed pCMB and
      pCMBS effects only when applied from the extracellular medium. l-Glutamate and l
      cystine, but not l-arginine, protected from the inactivation with an IC(50)
      similar to the K(m). Protection was not temperature-dependent, suggesting that it
      did not depend on large substrate-induced conformational changes. Mutation of
      Cys(327) to Ala and Ser slightly modified the K(m) and a C327L mutant abolished
      transport function without compromising transporter expression at the plasma
      membrane. The results indicate that Cys(327) is a functionally important residue
      accessible to the aqueous extracellular environment and is structurally linked to
      the permeation pathway and/or the substrate binding site.

PMID- 14722096
TI  - Protein tyrosine phosphatase-1B dephosphorylation of the insulin receptor occurs
      in a perinuclear endosome compartment in human embryonic kidney 293 cells.
AB  - Protein tyrosine phosphatase-1B (PTP-1B) is a negative regulator of insulin
      signaling. It is thought to carry out this role by interacting with and
      dephosphorylating the activated insulin receptor (IR). However, little is known
      regarding the nature of the cellular interaction between these proteins,
      especially because the IR is localized to the plasma membrane and PTP-1B to the
      endoplasmic reticulum. Using confocal microscopy and fluorescence resonance
      energy transfer (FRET), the interaction between PTP-1B and the IR was examined in
      co-transfected human embryonic kidney 293 cells. Biological activities were not
      significantly affected for either PTP-1B or the IR with the fusion of W1B-green
      fluorescent protein (GFP) to the N terminus of PTP-1B (W1B-PTP-1B) or the fusion
      of Topaz-GFP to the C terminus of the IR (Topaz-IR). FRET between W1B and Topaz
      was monitored in cells transfected with either wild type PTP-1B (W1B-PTP-1B) or
      the substrate-trapping form PTP-1B(D181A) (W1B-PTP-1B(D181A)) and Topaz-IR. Co
      expression of W1B-PTP-1B with Topaz-IR resulted in distribution of Topaz-IR to
      the plasma membrane, but no FRET was obtained upon insulin treatment. In
      contrast, co-expression of W1B-PTP-1B(D181A) with Topaz-IR caused an increase in
      cytosolic Topaz-IR fluorescence and, in some cells, a significant basal FRET
      signal, suggesting that PTP-1B is interacting with the IR during its synthesis.
      Stimulation of these cells with insulin resulted in a rapid induction of FRET
      that increased over time and was localized to a perinuclear spot. Co-expression
      of Topaz-IR with a GFP-labeled RhoB endosomal marker and treatment of the cells
      with insulin identified a perinuclear endosome compartment as the site of
      localization. Furthermore, the insulin-induced FRET could be prevented by the
      treatment of the cells with a specific PTP-1B inhibitor. These results suggest
      that PTP-1B appears not only to interact with and dephosphorylate the insulin
      stimulated IR in a perinuclear endosome compartment but is also involved in
      maintaining the IR in a dephosphorylated state during its biosynthesis.

PMID- 14722097
TI  - Granule localization of glutaminase in human neutrophils and the consequence of
      glutamine utilization for neutrophil activity.
AB  - The provision of glutamine in vivo has been observed to reduce to normal levels
      the neutrophilia observed after exhaustive exercise and to decrease the
      neutrophil chemoattractant, interleukin-8. Thus, the role for glutamine in the
      regulation of inflammatory mediators of human neutrophil activation was
      investigated. The study sought to establish whether glutamine supplementation in
      vitro affects neutrophil function at rest and whether glutaminase, the major
      enzyme that metabolizes glutamine, is present in human polymorphonuclear
      neutrophils (PMN). During in vitro studies, the addition of 2 mm glutamine
      increased the respiratory burst of human PMN stimulated with both phorbol
      myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine. These
      observations were made using a highly sensitive, real time chemiluminescent
      probe, Pholasin. Glutamine alone did not stimulate the release of reactive oxygen
      species. In a novel finding using glutaminase-specific antibodies in combination
      with flow cytometry and confocal microscopy, glutaminase was shown to be present
      on the surface of human PMN. Subcellular fractionation revealed that the enzyme
      was enriched in the secondary granules and could be released into cell culture
      medium upon stimulation with PMA. In conclusion, human PMN appeared to utilize
      glutamine and possess the appropriate glutaminase enzyme for metabolizing
      glutamine. This may depress some pro-inflammatory factors that occur during
      prolonged, exhaustive exercise.

PMID- 14722098
TI  - Familial hypertrophic cardiomyopathy mutations from different functional regions
      of troponin T result in different effects on the pH and Ca2+ sensitivity of
      cardiac muscle contraction.
AB  - To understand the molecular function of troponin T (TnT) in the Ca(2+) regulation
      of muscle contraction as well as the molecular pathogenesis of familial
      hypertrophic cardiomyopathy (FHC), eight FHC-linked TnT mutations, which are
      located in different functional regions of human cardiac TnT (HCTnT), were
      produced, and their structural and functional properties were examined. Circular
      dichroism spectroscopy demonstrated different secondary structures of these TnT
      mutants. Each of the recombinant HCTnTs was incorporated into porcine skinned
      fibers along with human cardiac troponin I (HCTnI) and troponin C (HCTnC), and
      the Ca(2+) dependent isometric force development of these troponin-replaced
      fibers was determined at pH 7.0 and 6.5. All eight mutants altered the
      contractile properties of skinned cardiac fibers. E244D potentiated the maximum
      force development without changing Ca(2+) sensitivity. In contrast, the other
      seven mutants increased the Ca(2+) sensitivity of force development but not the
      maximal force. R92L, R92W, and R94L also decreased the change in Ca(2+)
      sensitivity of force development observed on lowering the pH from 7 to 6.5, when
      compared with wild type TnT. The examination of additional mutants, H91Q and a
      double mutant H91Q/R92W, suggests that mutations in a region including residues
      91-94 in HCTnT can perturb the proper response of cardiac contraction to changes
      in pH. These results suggest that different regions of TnT may contribute to the
      pathogenesis of TnT-linked FHC through different mechanisms.

PMID- 14722099
TI  - Role of C-terminal extensions of subunits beta2 and beta7 in assembly and
      activity of eukaryotic proteasomes.
AB  - A close inspection of the crystal structure of the yeast 20 S proteasome revealed
      that a prominent connection between the two beta-rings is mediated by the subunit
      beta7/Pre4. Its C-terminal extension intercalates between the beta1/Pre3 and
      beta2/Pup1 subunits on the opposite ring. We show that the interactions promoted
      by the beta7/Pre4 tail are important to facilitate the formation of 20 S
      particles from two half-proteasome precursor complexes and/or to stabilize mature
      20 S proteasomes. The deletion of 19 residues from the beta7/Pre4 C terminus
      leads to an accumulation of half-proteasome precursor complexes containing the
      maturation factor Ump1. The C-terminal extension of beta7/Pre4, which forms
      several hydrogen bonds with beta1/Pre3, is in addition required for the post
      acidic activity mediated by the latter subunit. Deletion of the C-terminal tail
      of beta7/Pre4 results in an inhibition of beta1/Pre3 propeptide processing and
      abrogation of post-acidic activity. Our data obtained with yeast strains that
      expressed the mature form of Pre3 lacking its propeptide suggest that
      interactions between the Pre4 C terminus and Pre3 stabilize a conformation of its
      active site, which is essential for post-acidic activity. Deletion of the C
      terminal extension of beta2/Pup1, which wraps around beta3/Pup3 within the same
      beta-ring, is lethal, indicating that this extension serves an essential function
      in proteasome assembly or stability.

PMID- 14722100
TI  - Ryanodine receptor oligomeric interaction: identification of a putative binding
      region.
AB  - Specific interactions between adjacent ryanodine receptor (RyR) molecules to form
      ordered two-dimensional arrays in the membrane have been demonstrated using
      electron microscopy both in situ, in tissues and cells, and in vitro, with the
      purified protein. RyR interoligomeric association has also been inferred from
      observations of simultaneous channel gating during multi-RyR channel recordings
      in lipid bilayers. In this study, we report experiments designed to identify the
      region(s) of the RyR molecule, participating in this reciprocal interaction.
      Using epitope-specific antibodies, we identified a RyR tryptic fragment that
      specifically bound the intact immobilized RyR. Three overlapping RyR fragments
      encompassing this epitope, expressed using an in vitro mammalian expression
      system, were immunoprecipitated by RyR. To refine the binding regions, smaller
      RyR fragments were expressed as glutathione S-transferase (GST) fusion proteins,
      and their binding to RyR was monitored using a "sandwich" enzyme-linked
      immunosorbent assay. Three GST-RyR fusion proteins demonstrated specific binding,
      dependent upon ionic strength. Binding was greatest at 50-150 mm NaCl for two GST
      RyR constructs, and a third GST-RyR construct demonstrated maximum binding
      between 150 and 450 mm NaCl. The binding at high NaCl concentration suggested
      involvement of a hydrophobic interaction. In silico analysis of secondary
      structure showed evidence of coil regions in two of these RyR fragment sequences,
      which might explain these data. In GST pull-down assays, these same three
      fragments captured RyR2, and two of them retained RyR1. These results identify a
      region at the center of the linear RyR (residues 2540-3207 of human RyR2) which
      is able to bind to the RyR oligomer. This region may constitute a specific
      subdomain participating in RyR-RyR interaction.

PMID- 14722101
TI  - Overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene prevents
      acetaldehyde-induced cell injury in human umbilical vein endothelial cells: role
      of ERK and p38 mitogen-activated protein kinase.
AB  - Acetaldehyde, the major ethanol metabolite that is far more toxic and reactive
      than ethanol, has been postulated to be responsible for alcohol-induced tissue
      and cell injury. This study was to examine whether facilitated acetaldehyde
      metabolism affects acetaldehyde-induced oxidative stress and apoptosis. Transgene
      encoding human aldehyde dehydrogenase-2 (ALDH2), which converts acetaldehyde into
      acetate, was constructed under chicken beta-actin promoter and transfected into
      human umbilical vein endothelial cells (HUVECs). Efficacy of ALDH2 transfection
      was verified using green fluorescent protein and ALDH2 enzymatic assay.
      Generation of reactive oxygen species (ROS) was measured using chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by 4',6'-diamidino
      2'-phenylindoladihydrochloride fluorescence microscopy, quantitative DNA
      fragmentation, and caspase-3 assay. Acetaldehyde (0-200 microm) elicited ROS
      generation and apoptosis in HUVECs in a time- and concentration-dependent manner,
      associated with activation of the stress signal molecules ERK1/2 and p38 mitogen
      activated protein (MAP) kinase. A close liner correlation was observed between
      the acetaldehyde-induced ROS generation and apoptosis. Interestingly, the
      acetaldehyde-induced ROS generation, apoptosis, activation of ERK1/2, and p38 MAP
      kinase were prevented by the ALDH2 transgene or antioxidant alpha-tocopherol. The
      involvement of ERK1/2 and p38 MAP kinase in acetaldehyde-induced apoptosis was
      confirmed by selective kinase inhibitors U0126, SB203580, and SB202190.
      Collectively, our data revealed that facilitation of acetaldehyde metabolism by
      ALDH2 transgene overexpression may prevent acetaldehyde-induced cell injury and
      activation of stress signals. These results indicated therapeutic potential of
      ALDH2 enzyme in the prevention and detoxification of acetaldehyde or alcohol
      induced cell injury.

PMID- 14722102
TI  - Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase
      related protein (IGRP).
AB  - Glucose is the main physiological stimulus for insulin biosynthesis and secretion
      by pancreatic beta-cells. Glucose-6-phosphatase (G-6-Pase) catalyzes the
      dephosphorylation of glucose-6-phosphate to glucose, an opposite process to
      glucose utilization. G-6-Pase activity in pancreatic islets could therefore be an
      important factor in the control of glucose metabolism and, consequently, of
      glucose-dependent insulin secretion. While G-6-Pase activity has been shown to be
      present in pancreatic islets, the gene responsible for this activity has not been
      conclusively identified. A homolog of liver glucose-6-phosphatase (LG-6-Pase)
      specifically expressed in islets was described earlier; however, the authors
      could not demonstrate enzymatic activity for this protein. Here we present
      evidence that the previously identified islet-specific glucose-6-phosphatase
      related protein (IGRP) is indeed the major islet glucose-6-phosphatase. IGRP
      overexpressed in insect cells possesses enzymatic activity comparable to the
      previously described G-6-Pase activity in islets. The K(m) and V(max) values
      determined using glucose-6-phosphate as the substrate were 0.45 mm and 32
      nmol/mg/min by malachite green assay, and 0.29 mm and 77 nmol/mg/min by glucose
      oxidase/peroxidase coupling assay, respectively. High-throughput screening of a
      small molecule library led to the identification of an active compound that
      specifically inhibits IGRP enzymatic activity. Interestingly, this inhibitor did
      not affect LG-6-Pase activity, while conversely LG-6-Pase inhibitors did not
      affect IGRP activity. These data demonstrate that IGRP is likely the authentic
      islet-specific glucose-6-phosphatase catalytic subunit, and selective inhibitors
      to this molecule can be obtained. IGRP inhibitors may be an attractive new
      approach for the treatment of insulin secretion defects in type 2 diabetes.

PMID- 14722103
TI  - Rabphilin and Noc2 are recruited to dense-core vesicles through specific
      interaction with Rab27A in PC12 cells.
AB  - Rabphilin and Noc2 were originally described as Rab3A effector proteins involved
      in the regulation of secretory vesicle exocytosis, however, recently both
      proteins have been shown to bind Rab27A in vitro in preference to Rab3A (Fukuda,
      M. (2003) J. Biol. Chem. 278, 15373-15380), suggesting that Rab3A is not their
      major ligand in vivo. In the present study we showed by means of deletion and
      mutation analyses that rabphilin and Noc2 are recruited to dense-core vesicles
      through specific interaction with Rab27A, not with Rab3A, in PC12 cells. Rab3A
      binding-defective mutants of rabphilin(E50A) and Noc2(E51A) were still localized
      in the distal portion of the neurites (where dense-core vesicles had accumulated)
      in nerve growth factor-differentiated PC12 cells, the same as the wild-type
      proteins, whereas Rab27A binding-defective mutants of rabphilin(E50A/I54A) and
      Noc2(E51A/I55A) were present throughout the cytosol. We further showed that
      expression of the wild-type or the E50A mutant of rabphilin-RBD, but not the
      E50A/I54A mutant of rabphilin-RBD, significantly inhibited high KCl-dependent
      neuropeptide Y secretion by PC12 cells. We also found that rabphilin and its
      binding partner, Rab27 have been highly conserved during evolution (from nematoda
      to humans) and that Caenorhabditis elegans and Drosophila rabphilin (ce/dm
      rabphilin) specifically interact with ce/dm-Rab27, but not with ce/dm-Rab3 or
      ce/dm-Rab8, suggesting that rabphilin functions as a Rab27 effector across
      phylogeny. Based on these findings, we propose that the N-terminal Rab binding
      domain of rabphilin and Noc2 be referred to as "RBD27 (Rab binding domain for
      Rab27)", the same as the synaptotagmin-like protein homology domain (SHD) of
      Slac2-a/melanophilin.

PMID- 14722104
TI  - Regulation of casein kinase I epsilon activity by Wnt signaling.
AB  - The Wnt/beta-catenin signaling pathway is important in both development and
      cancer. Casein kinase Iepsilon (CKIepsilon) is a positive regulator of the
      canonical Wnt pathway. CKIepsilon itself can be regulated in vitro by inhibitory
      autophosphorylation, and recent data suggest that in vivo kinase activity can be
      regulated by extracellular stimuli. We show here that the phosphorylation state
      and kinase activity of CKIepsilon are directly regulated by Wnt signaling.
      Coexpression of XWnt-8 or addition of soluble Wnt-3a ligand led to a significant
      and rapid increase in the activity of endogenous CKIepsilon. The increase in
      CKIepsilon activity is the result of decreased inhibitory autophosphorylation
      because it is abolished by preincubation of immunoprecipitated kinase with ATP.
      Furthermore, mutation of CKIepsilon inhibitory autophosphorylation sites creates
      a kinase termed CKIepsilon(MM2) that is significantly more active than CKIepsilon
      and is not activated further upon Wnt stimulation. Autoinhibition of CKIepsilon
      is biologically relevant because CKIepsilon(MM2) is more effective than
      CKIepsilon at activating transcription from a Lef1-dependent promoter. Finally,
      CKIepsilon(MM2) expression in Xenopus embryos induces both axis duplication and
      additional developmental abnormalities. The data suggest that Wnt signaling
      activates CKIepsilon by causing transient dephosphorylation of critical
      inhibitory sites present in the carboxyl-terminal domain of the kinase.
      Activation of the Wnt pathway may therefore stimulate a cellular phosphatase to
      dephosphorylate and activate CKIepsilon

PMID- 14722105
TI  - Sphingolipids as bioactive regulators of thrombin generation.
AB  - Sphingolipids contribute to modulation of two opposing cell processes, cell
      growth and apoptotic cell death; ceramide and sphingosine promote the latter and
      sphingosine-1-phosphate triggers the former. Thrombin, a pro-inflammatory
      protease that is regulated by the blood coagulation cascade, exerts similar
      effects depending on cell type. Here we report a new mechanism for cross-talk
      between sphingolipid metabolism and thrombin generation. Sphingosine and
      sphinganine, but not ceramide or sphingosine-1-phosphate, down-regulated thrombin
      generation on platelet surfaces (IC(50) = 2.4 and 1.4 microm for sphingosine and
      sphinganine, respectively) as well as in whole plasma clotting assays. Thrombin
      generation was also inhibited by glucosylsphingosine, lysosphingomyelin,
      phytosphingosine, and primary alkylamines with >10 carbons. Acylation of the
      amino group ablated anticoagulant activities. Factor Va was required for the
      anticoagulant property of sphingosine because prothrombin activation was
      inhibited by sphingosine, sphinganine, and stearylamine in the presence but not
      in the absence of factor Va. Sphingosine did not inhibit thrombin generation when
      Gla-domainless factor Xa was used in prothrombinase assays, whereas sphingosine
      inhibited activation of Gla-domainless prothrombin by factor Xa/factor Va in the
      absence of phospholipids (IC(50) = 0.49 microm). Fluorescence spectroscopy
      studies showed that sphingosine binds to fluorescein-labeled factor Xa and that
      this interaction required the Gla domain. These results imply that sphingosine
      disrupts interactions between factor Va and the Gla domain of factor Xa in the
      prothrombinase complex. Thus, certain sphingolipids may be bioactive lipid
      mediators of thrombin generation such that certain sphingolipid metabolites may
      modulate proteases that affect cell growth and death, blood coagulation, and
      inflammation.

PMID- 14722106
TI  - The calcineurin/nuclear factor of activated T cells signaling pathway regulates
      osteoclastogenesis in RAW264.7 cells.
AB  - Although best known for its role in T lymphocyte activation, the
      calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway is also
      known to be involved in a wide range of other biological responses in a variety
      of different cell types. Here we have investigated the role of the
      calcineurin/NFAT signaling pathway in the regulation of osteoclast
      differentiation. Osteoclasts are bone-resorbing multinucleated cells that are
      derived from the monocyte/macrophage cell lineage after stimulation with a member
      of the tumor necrosis factor family of ligands known as receptor activator of
      nuclear factor-kappaB ligand (RANKL). We now report that inhibition of
      calcineurin with either the immunosuppressant drugs cyclosporin A and FK506, or
      the retrovirally mediated ectopic expression of a specific calcineurin inhibitory
      peptide, all potently inhibit the RANKL-induced differentiation of the RAW264.7
      monocyte/macrophage cell line into mature multinucleated osteoclasts. In
      addition, we find that NFAT family members are expressed in RAW264.7 cells and
      that their expression is up-regulated in response to RANKL stimulation. Most
      importantly, we find that ectopic expression of a constitutively active,
      calcineurin-independent NFATc1 mutant in RAW264.7 cells is sufficient to induce
      these cells to express an osteoclast-specific pattern of gene expression and
      differentiate into morphologically distinct, multinucleated osteoclasts capable
      of inducing the resorption of a physiological mineralized matrix substrate. Taken
      together, these data define calcineurin as an essential downstream effector of
      the RANKL-induced signal transduction pathway leading toward the induction of
      osteoclast differentiation and furthermore, indicate that the activation of the
      NFATc1 transcription factor is sufficient to initiate a genetic program that
      results in the specification of the mature functional osteoclast cell phenotype.

PMID- 14722107
TI  - Defining a molecular mechanism of synergy between nucleoside and nonnucleoside
      AIDS drugs.
AB  - Combination therapies treating human immunodeficiency virus type 1 (HIV-1)
      infection delay the emergence of drug-resistant virus and exhibit synergistic
      inhibition. This synergy is observed within the two classes of inhibitors that
      target the essential viral reverse transcriptase (RT): the chain-terminating
      nucleoside analogs (NRTIs) and the allosteric nonnucleosides (NNRTIs) that bind
      in a pocket distinct from the active site. A general mechanism to define the
      molecular basis for synergy between these two classes remains to be elucidated.
      Previous mechanistic studies from our laboratory (Spence, R. A., Kati, W. M.,
      Anderson, K. S., and Johnson, K. A. (1995) Science 267, 988-993) have shown that
      the natural deoxynucleoside triphosphate and the NNRTI can simultaneously bind to
      their respective sites. This work also suggests communication between the two
      sites, since the inhibition of RT by NNRTIs is manifested through a remote effect
      on the chemical step. This interplay between the two sites offers a plausible
      hypothesis for understanding synergy in which binding of NNRTIs modulates the
      chain termination by NRTIs. The present study supports this hypothesis by
      illustrating that the clinically approved NNRTIs, nevirapine and efavirenz,
      inhibit the ATP-mediated removal of AZTMP, d4TMP, ddCMP, (-)3TCMP, (-)FTCMP, and
      (+)3TCMP, thereby prolonging the effectiveness of chain termination. This
      inhibition is mediated through an effect on both the rate of the chemical step
      and binding of ATP, resulting in an overall decrease in efficiency of removal.
      This work substantiates communication between the two binding pockets, the
      sustained use of combination therapy to treat HIV infection, and a molecular
      basis for understanding synergy.

PMID- 14722108
TI  - Myocyte enhancer factor 2 mediates calcium-dependent transcription of the
      interleukin-2 gene in T lymphocytes: a calcium signaling module that is distinct
      from but collaborates with the nuclear factor of activated T cells (NFAT).
AB  - The second messenger calcium plays an essential role in the T cell receptor
      mediated signal transduction pathways leading to transcription of the interleukin
      2 gene. A key mechanism of calcium signaling has been shown to be mediated by
      calcineurin and NFAT. We report herein that the transcription factor myocyte
      enhancer factor (MEF)-2 is another calcium signal transducer involved in the
      regulation of the interleukin (IL)-2 promoter. A MEF2-binding site was identified
      in proximity to the TATA box of the IL-2 promoter. This site was shown to be
      bound by MEF2 in both resting and activated T cells. Overexpression of MEF2
      enhanced, while overexpression of a dominant negative form of MEF2 or the MEF2
      specific transcriptional corepressors Cabin1 and histone deacetylase 4 inhibited,
      the T cell receptor-dependent activation of an IL-2 reporter gene. Down
      regulation of MEF2 by RNA interference in primary human T cells led to the
      inhibition of endogenous IL-2 transcription. These results suggest that MEF2 is
      required for the transcriptional activation of IL-2 and likely other cytokine
      genes in response to calcium signaling and may serve as a novel target for
      development of immunosuppressants.

PMID- 14722109
TI  - Modulation of cardiac Ca2+ channel by Gq-activating neurotransmitters
      reconstituted in Xenopus oocytes.
AB  - L-type dihydropyridine-sensitive voltage dependent Ca(2+) channels (L-VDCCs;
      alpha(1C)) are crucial in cardiovascular physiology. Currents via L-VDCCs are
      enhanced by hormones and transmitters operating via G(q), such as angiotensin II
      (AngII) and acetylcholine (ACh). It has been proposed that these modulations are
      mediated by protein kinase C (PKC). However, reports on effects of PKC activators
      on L-type channels are contradictory; inhibitory and/or enhancing effects have
      been observed. Attempts to reproduce the enhancing effect of AngII in
      heterologous expression systems failed. We previously found that PKC modulation
      of the channel depends on alpha(1C) isoform used; only a long N-terminal (NT)
      isoform was up-regulated. Here we report the reconstitution of the AngII- and ACh
      induced enhancement of the long-NT isoform of L-VDCC expressed in Xenopus
      oocytes. The current initially increased over several minutes but later declined
      to below baseline levels. Using different NT deletion mutants and human short-
      and long-NT isoforms of the channel, we found the initial segment of the NT to be
      crucial for the enhancing, but not for the inhibitory, effect. Using blockers of
      PKC and of phospholipase C (PLC) and a mutated AngII receptor lacking G(q)
      coupling, we demonstrate that the signaling pathway of the enhancing effect
      includes the activation of G(q), PLC, and PKC. The inhibitory modulation, present
      in both alpha(1C) isoforms, was G(q)- and PLC-independent and Ca(2+)-dependent,
      but not Ca(2+)-mediated, as only basal levels of Ca(2+) were essential.
      Reconstitution of AngII and ACh effects in Xenopus oocytes will advance the study
      of molecular mechanisms of these physiologically important modulations.

PMID- 14722110
TI  - Saccharomyces cerevisiae glutaredoxin 5-deficient cells subjected to continuous
      oxidizing conditions are affected in the expression of specific sets of genes.
AB  - The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin
      involved in the synthesis of iron/sulfur clusters. Its absence prevents
      respiratory growth and causes the accumulation of iron inside cells and
      constitutive oxidation of proteins. Null Deltagrx5 mutants were used as an
      example of continuously oxidized cells, as opposed to situations in which
      oxidative stress is instantaneously caused by addition of external oxidants.
      Whole transcriptome analysis was carried out in the mutant cells. The set of
      genes whose expression was affected by the absence of Grx5 does not significantly
      overlap with the set of genes affected in respiratory petite mutants. Many Aft1
      dependent genes involved in iron utilization that are up-regulated in a frataxin
      mutant were also up-regulated in the absence of Grx5. BIO5 is another Aft1
      dependent gene induced both upon iron deprivation and in Deltagrx5 cells; this
      links iron and biotin metabolism. Other genes are specifically affected under the
      oxidative conditions generated by the grx5 mutation. One of these is MLP1, which
      codes for a homologue of the Slt2 kinase. Cells lacking MLP1 and GRX5 are
      hypersensitive to oxidative stress caused by external agents and exhibit
      increased protein oxidation in relation to single mutants. This in turn points to
      a role for Mlp1 in protection against oxidative stress. The genes of the Hap4
      regulon, which are involved in respiratory metabolism, are down-regulated in
      Deltagrx5 cells. This effect is suppressed by HAP4 overexpression. Inhibition of
      respiratory metabolism during continuous moderately oxidative conditions could be
      a protective response by the cell.

PMID- 14722111
TI  - Structure-function analysis of the human sialyltransferase ST3Gal I: role of n
      glycosylation and a novel conserved sialylmotif.
AB  - All eukaryotic sialyltransferases have in common the presence in their catalytic
      domain of several conserved peptide regions (sialylmotifs L, S, and VS).
      Functional analysis of sialylmotifs L and S previously demonstrated their
      involvement in the binding of donor and acceptor substrates. The region comprised
      between the sialylmotifs S and VS contains a stretch of four highly conserved
      residues, with the following consensus sequence (H/y)Y(Y/F/W/h)(E/D/q/g).
      (Capital letters and lowercase letters indicate a strong or low occurrence of the
      amino acid, respectively.) The functional importance of these residues and of the
      conserved residues of motif VS (HX(4)E) was assessed using as a template the
      human ST3Gal I. Mutational analysis showed that residues His(299) and Tyr(300) of
      the new motif, and His(316) of the VS motif, are essential for activity since
      their substitution by alanine yielded inactive enzymes. Our results suggest that
      the invariant Tyr residue (Tyr(300)) plays an important conformational role
      mainly attributable to the aromatic ring. In contrast, the mutants W301F, E302Q,
      and E321Q retained significant enzyme activity (25-80% of the wild type). Kinetic
      analyses and CDP binding assays showed that none of the mutants tested had any
      significant effect in nucleotide donor binding. Instead the mutant proteins were
      affected in their binding to the acceptor and/or demonstrated lower catalytic
      efficiency. Although the human ST3Gal I has four N-glycan attachment sites in its
      catalytic domain that are potentially glycosylated, none of them was shown to be
      necessary for enzyme activity. However, N-glycosylation appears to contribute to
      the proper folding and trafficking of the enzyme.

PMID- 14722112
TI  - 5-aza-2'-deoxycytidine activates the p53/p21Waf1/Cip1 pathway to inhibit cell
      proliferation.
AB  - In addition to its demethylating function, 5-aza-2'-deoxycytidine (5-aza-CdR)
      also plays an important role in inducing cell cycle arrest, differentiation, and
      cell death. However, the mechanism by which 5-aza-CdR induces antineoplastic
      activity is not clear. In this study, we found that 5-aza-CdR at limited
      concentrations (0.01-5 microm) induces inhibition of cell proliferation as well
      as increased p53/p21(Waf1/Cip1) expression in A549 cells (wild-type p53) but not
      in H1299 (p53-null) and H719 cells (p53 mutant). The p53-dependent p21(Waf1/Cip1)
      expression induced by 5-aza-CdR was not seen in A549 cells transfected with the
      wild-type human papilloma virus type-16 E6 gene that induces p53 degradation.
      Furthermore, deletion analysis and site-directed mutagenesis of the p21 promoter
      reveals that 5-aza-CdR induces p21(Waf1/Cip1) expression through two p53 binding
      sites in the p21 promoter. Finally, 5-aza-CdR-induced p21(Waf1/Cip1) expression
      was dependent on DNA damage but not on DNA demethylation as demonstrated by comet
      assay and bisulfite sequencing, respectively. Our data provide useful clues for
      judging the therapeutic efficacy of 5-aza-CdR in the treatment of human cancer
      cells.

PMID- 14722113
TI  - Identification of a novel NF-kappaB-binding site with regulation of the murine
      alpha2(I) collagen promoter.
AB  - Hepatic fibrosis is due to the increased synthesis and deposition of type I
      collagen. Acetaldehyde activates type I collagen promoters. Nuclear factor kappaB
      (NF-kappaB) was previously shown to inhibit expression of murine alpha(1)(I) and
      human alpha(2)(I) collagen promoters. The present study identifies binding of NF
      kappaB, present in nuclear extracts of stellate cells, to a region between -553
      and -537 of the murine alpha(2)(I) collagen promoter. The NF-kappaB (p65)
      expression vector inhibited promoter activity. Mutation of the promoter at the NF
      kappaB-binding site increased basal promoter activity and abrogated the
      activating and inhibitory effects of transforming growth factor beta and tumor
      necrosis factor alpha, respectively, on promoter activity. Acetaldehyde increased
      IkappaB-alpha kinase activity and phosphorylated IkappaB-alpha, NF-kappaB nuclear
      protein, and its binding to the promoter. However, the activating effect of
      acetaldehyde was not affected by the mutation of the promoter. In conclusion,
      although acetaldehyde increases the binding of NF-kappaB to the murine
      alpha(2)(I) collagen promoter, this binding does not mediate the activating
      effect of acetaldehyde on promoter activity. The effects of acetaldehyde in
      increasing the translocation of NF-kappaB to the nucleus with increased DNA
      binding activity may be important in mediating the effects of acetaldehyde on
      other genes.

PMID- 14722115
TI  - Energy-dependent transformation of F0.F1-ATPase in Paracoccus denitrificans
      plasma membranes.
AB  - F(0).F(1)-ATP synthase in tightly coupled inside-out vesicles derived from
      Paracoccus denitrificans catalyzes rapid respiration-supported ATP synthesis,
      whereas their ATPase activity is very low. In the present study, the conditions
      required to reveal the Deltamu(H+)-generating ATP hydrolase activity of the
      bacterial enzyme have been elucidated. Energization of the membranes by
      respiration results in strong activation of the venturicidin-sensitive ATP
      hydrolysis, which is coupled with generation of Deltamu(H+). Partial uncoupling
      stimulates the proton-translocating ATP hydrolysis, whereas complete uncoupling
      results in inhibition of the ATPase activity. The presence of inorganic phosphate
      is indispensable for the steady-state turnover of the Deltamu(H+)-activated
      ATPase. The collapse of Deltamu(H+) brings about rapid deactivation of the
      enzyme, which has been subjected to pre-energization. The rate and extent of the
      deactivation depend on protein concentration, i.e. the more vesicles are present
      in the assay mixture, the higher the rate and extent of the deactivation is seen.
      Sulfite and the ADP-trapping system protect ATPase against the Deltamu(H+)
      collapse-induced deactivation, whereas phosphate delays the rate of deactivation.
      A low concentration of ADP (<1 microm) increases the rate of deactivation. Taken
      together, the results suggest that latent proton-translocating ATPase in P.
      denitrificans is kinetically equivalent to the previously characterized ADP(Mg2+)
      inhibited, azide-trapped bovine heart mitochondrial F(0).F(1)-ATPase (Galkin, M.
      A., and Vinogradov, A. D. (1999) FEBS Lett. 448, 123-126). A Deltamu(H+)
      sensitive mechanism operates in P. denitrificans that prevents physiologically
      wasteful consumption of ATP by F(0).F(1)-ATPase (synthase) complex when the
      latter is unable to maintain certain value of Deltamu(H+).

PMID- 14722114
TI  - Identification of proline residues in the core cytoplasmic and transmembrane
      regions of multidrug resistance protein 1 (MRP1/ABCC1) important for transport
      function, substrate specificity, and nucleotide interactions.
AB  - Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-binding cassette
      transporter that confers resistance to drugs and mediates the transport of
      organic anions. MRP1 has a core structure of two membrane spanning domains (MSDs)
      each followed by a nucleotide binding domain. This core structure is preceded by
      a third MSD with five transmembrane (TM) helices, whereas MSD2 and MSD3 each
      contain six TM helices. We investigated the consequences of Ala substitution of
      18 Pro residues in both the non-membrane and TM regions of MSD2 and MSD3 on MRP1
      expression and organic anion transport function. All MRP1-Pro mutants except
      P1113A were expressed in human embryonic kidney cells at levels comparable with
      wild-type MRP1. In addition, five mutants containing substitutions of Pro
      residues in or proximal to the TM helices of MSD2 (TM6-Pro(343), TM8-Pro(448),
      TM10-Pro(557), and TM11-Pro(595)) and MSD3 (TM14-Pro(1088)) exhibited
      significantly reduced transport of five organic anion substrates. In contrast,
      mutation of Pro(1150) in the cytoplasmic loop (CL7) linking TM15 to TM16 caused a
      substantial increase in 17beta-estradiol-17-beta-(D-glucuronide) and methotrexate
      transport, whereas transport of other organic anions was reduced or unchanged.
      Significant substrate-specific changes in the ATP dependence of transport and
      binding by the P1150A mutant were also observed. Our findings demonstrate the
      importance of TM6, TM8, TM10, TM11, and TM14 in MRP1 transport function and
      suggest that CL7 may play a differential role in coupling the activity of the
      nucleotide binding domains to the translocation of different substrates across
      the membrane.

PMID- 14722116
TI  - The importance of three membrane-distal tyrosines in the adaptor protein
      NTAL/LAB.
AB  - NTAL (non-T cell activation linker)/LAB (linker for activation of B cells) is a
      LAT (linker for activation of T cells)-like molecule that is expressed in B
      cells, mast cells, natural killer cells, and monocytes. Upon engagement of the B
      cell receptor or Fc receptors, it is phosphorylated and interacts with Grb2. LAB
      is capable of rescuing thymocyte development in LAT(-/-) mice. In this study, we
      utilized various LAB Tyr to Phe mutants to map the phosphorylation and Grb2
      binding sites of LAB. We also examined the function of these mutants by
      investigating their ability to rescue signaling defects in LAT-deficient Jurkat
      cells and thymocyte development in LAT(-/-) mice. Our results indicated that
      human LAB was primarily phosphorylated on three membrane-distal tyrosines,
      Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished
      Grb2 binding and LAB function. Our data suggested that these tyrosines are the
      most important tyrosines for LAB function.

PMID- 14722117
TI  - The effect of zeaxanthin as the only xanthophyll on the structure and function of
      the photosynthetic apparatus in Arabidopsis thaliana.
AB  - In green plants, the xanthophyll carotenoid zeaxanthin is synthesized transiently
      under conditions of excess light energy and participates in photoprotection. In
      the Arabidopsis lut2 npq2 double mutant, all xanthophylls were replaced
      constitutively by zeaxanthin, the only xanthophyll whose synthesis was not
      impaired. The relative proportions of the different chlorophyll antenna proteins
      were strongly affected with respect to the wild-type strain. The major antenna,
      LHCII, did not form trimers, and its abundance was strongly reduced as was CP26,
      albeit to a lesser extent. In contrast, CP29, CP24, LHCI proteins, and the PSI
      and PSII core complexes did not undergo major changes. PSII-LHCII supercomplexes
      were not detectable while the PSI-LHCI supercomplex remained unaffected. The
      effect of zeaxanthin accumulation on the stability of the different Lhc proteins
      was uneven: the LHCII proteins from lut2 npq2 had a lower melting temperature as
      compared with the wild-type complex while LHCI showed increased resistance to
      heat denaturation. Consistent with the loss of LHCII, light-state 1 to state 2
      transitions were suppressed, the photochemical efficiency in limiting light was
      reduced and photosynthesis was saturated at higher light intensities in lut2 npq2
      leaves, resulting in a photosynthetic phenotype resembling that of high light
      acclimated leaves. Zeaxanthin functioned in vivo as a light-harvesting accessory
      pigment in lut2 npq2 chlorophyll antennae. As a whole, the in vivo data are
      consistent with the results obtained by using recombinant Lhc proteins
      reconstituted in vitro with purified zeaxanthin. While PSII photoinhibition was
      similar in wild type and lut2 npq2 exposed to high light at low temperature, the
      double mutant was much more resistant to photooxidative stress and lipid
      peroxidation than the wild type. The latter observation is consistent with an
      antioxidant and lipid protective role of zeaxanthin in vivo.

PMID- 14722118
TI  - Autophosphorylation of a newly identified site of Aurora-B is indispensable for
      cytokinesis.
AB  - Mitotic kinases regulate cell division and its checkpoints, errors of which can
      lead to aneuploidy or genetic instability. One of these is Aurora-B, a key kinase
      that is required for chromosome alignment at the metaphase plate and for
      cytokinesis in mammalian cells. We report here that human Aurora-B is
      phosphorylated at Thr-232 through interaction with the inner centromere protein
      (INCENP) in vivo. The phosphorylation of Thr-232 occurs by means of an
      autophosphorylation mechanism, which is indispensable for the Aurora-B kinase
      activity. The activation of Aurora-B spatio-temporally correlated with the site
      specific phosphorylation of its physiological substrates, histone H3 and
      vimentin. Overexpression of the TA mutant of Aurora-B, in which Thr-232 was
      changed into alanine, frequently induced multinuclearity in cells. These results
      indicate that the phosphorylation of Thr-232 is an essential regulatory mechanism
      for Aurora-B activation.

PMID- 14722119
TI  - Bidirectional regulation of neuronal nitric-oxide synthase phosphorylation at
      serine 847 by the N-methyl-D-aspartate receptor.
AB  - At glutamatergic synapses, the scaffolding protein PSD95 links the neuronal
      isoform of nitric-oxide synthase (nNOS) to the N-methyl-d-aspartate (NMDA)
      receptor. Phosphorylation of nNOS at serine 847 (Ser(847)) by the calcium
      calmodulin protein kinase II (CaMKII) inhibits nNOS activity, possibly by
      blocking the binding of Ca(2+)-CaM. Here we show that the NMDA mediates a novel
      bidirectional regulation of Ser(847) phosphorylation. nNOS phosphorylated at
      Ser(847) colocalizes with the NMDA receptor at spines of cultured hippocampal
      neurons. Treatment of neurons with 5 microm glutamate stimulated CaMKII
      phosphorylation of nNOS at Ser(847), whereas excitotoxic concentrations of
      glutamate, 100 and 500 microm, induced Ser(847)-PO(4) dephosphorylation by
      protein phosphatase 1. Strong NMDA receptor stimulation was likely to activate
      nNOS under these conditions because protein nitration to form nitrotyrosine, a
      marker of nNOS activity, correlated in individual neurons with Ser(847)-PO(4)
      dephosphorylation. Of particular note, stimulation with low glutamate that
      increased phosphorylation of nNOS at Ser(847) could be reversed by subsequent
      high glutamate treatment which induced dephosphorylation. The reversibility of
      NMDA receptor-induced phosphorylation at Ser(847) by different doses of glutamate
      suggests two mechanisms with opposite effects: 1). a time-dependent negative
      feedback induced by physiological concentrations of glutamate that limits nNOS
      activation and precludes the overproduction of NO; and 2). a pathological
      stimulation by high concentrations of glutamate that leads to unregulated nNOS
      activation and production of toxic levels of NO. These mechanisms may share
      pathways, respectively, with NMDA receptor-induced forms of synaptic plasticity
      and excitotoxicity.

PMID- 14722120
TI  - The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on
      angiogenesis.
AB  - NTAK (neural- and thymus-derived activator for ErbB kinases), also known as
      neuregulin-2, is a member of the epidermal growth factor (EGF) family, which
      binds directly to ErbB3 and ErbB4 and transactivates ErbB2. Because ErbB
      signaling has been implicated in various angiogenic mechanisms, the effect of
      NTAK (which has at least nine isoforms due to alternative splicing) in
      angiogenesis is explored. One isoform, NTAKgamma, inhibited cell growth in terms
      of DNA synthesis and cell numbers in vascular endothelial cells specifically,
      whereas NTAKalpha and beta had no activity. On the other hand, NTAKgamma secreted
      by transfected MDA-MB-231 cells inhibited endothelial cell growth, and NTAKgamma
      expressed in endothelial cells by adenovirus infection suppressed cell growth in
      a dose-dependent manner. The EGF-like domain of NTAKgamma did not have this
      activity. The NTAKdelta isoform, which had the Ig-like domain but not the EGF
      like domain, inhibited proliferation of endothelial cells. NTAKdelta prevented
      hyper-phosphorylation of the retinoblastoma tumor suppressor protein and caused
      G(1) arrest in endothelial cells. Both NTAKgamma and delta isoforms displayed
      anti-angiogenic activity in the chick embryo chorioallantoic membrane in vivo.
      These results suggest that the active site of NTAK is localized outside of the
      EGF-like domain but within the N-terminal region, including the Ig-like domain,
      of NTAK.

PMID- 14722121
TI  - Residues 110-126 in the A1 domain of factor VIII contain a Ca2+ binding site
      required for cofactor activity.
AB  - Generation of factor VIII cofactor activity requires divalent metal ions such as
      Ca2+ or Mn2+. Evaluation of cofactor reconstitution from isolated factor VIIIa
      subunits revealed the presence of a functional Ca2+ binding site within the A1
      subunit. Isothermal titration calorimetry demonstrated at least two Ca2+ binding
      sites of similar affinity (K(d) = 0.74 microm) within the A1 subunit. Mutagenesis
      of an acidic residue-rich region in the A1 domain (residues 110-126) homologous
      to a putative Ca2+ binding site in factor V (Zeibdawi, A. R., and Pryzdial, E. L.
      (2001) J. Biol. Chem. 276, 19929-19936) and expression of B-domainless factor
      VIII molecules yielded reagents to probe Ca2+ and Mn2+ binding in a functional
      assay. Basal activity observed for wild type factor VIII in a metal ion-free
      buffer was enhanced approximately 2-fold with saturating Ca2+ or Mn2+ and yielded
      functional K(d) values of 1.2 and 1.40 microm, respectively. Ca2+ binding
      affinity was greatly reduced (or lost) in several mutants including E110A, E110D,
      D116A, E122A, D125A, and D126A. Alternatively, E113A, D115A, and E124A showed
      wild type-like activity with little or no reduction in Ca2+ affinity. However,
      Mn2+ affinity was minimally altered except for mutant D125A (and D116A). These
      results are consistent with region 110-126 serving a critical role for Ca2+
      coordination with selected residues capable of contributing to a partially
      overlapping site for Mn2+, and that occupancy of either site is required for
      maximal cofactor activity.

PMID- 14722122
TI  - Induction of survivin expression by taxol (paclitaxel) is an early event, which
      is independent of taxol-mediated G2/M arrest.
AB  - Survivin is a novel anti-apoptotic protein that is highly expressed in cancer but
      is undetectable in most normal adult tissues. It was reported that taxol-mediated
      mitotic arrest of cancer cells is associated with survivin induction, which
      preserves a survival pathway and results in resistance to taxol. In this study,
      we provide new evidence that induction of survivin by taxol is an early event and
      is independent of taxol-mediated G(2)/M arrest. Taxol treatment of MCF-7 cells
      rapidly up-regulated survivin expression (3.5-15-fold) within 4 h without G(2)/M
      arrest. Lengthening the treatment of cells (48 h) with taxol resulted in
      decreased survivin expression in comparison with early times following taxol
      treatment, although G(2)/M cells were significantly increased at later times.
      Interestingly, 3 nm taxol induces survivin as effectively as 300 nm and more
      effectively than 3000 nm. As a result, 3 nm taxol is ineffective at inducing cell
      death. However, inhibition of taxol-mediated survivin induction by small
      interfering RNA significantly increased taxol-mediated cell death. Taxol rapidly
      activated the phosphatidylinositol 3-kinase/Akt and MAPK pathways. Inhibition of
      these pathways diminished survivin induction and sensitized cells to taxol
      mediated cell death. A cis-acting DNA element upstream of -1430 in the survivin
      pLuc-2840 construct is at least partially responsible for taxol-mediated survivin
      induction. Together, these data show, for the first time, that taxol-mediated
      induction of survivin is an early event and independent of taxol-mediated G(2)/M
      arrest. This appears to be a new mechanism for cancer cells to evade taxol
      induced apoptosis. Targeting this survival pathway may result in novel approaches
      for cancer therapeutics.

PMID- 14722123
TI  - N terminus is essential for tropomyosin functions: N-terminal modification
      disrupts stress fiber organization and abolishes anti-oncogenic effects of
      tropomyosin-1.
AB  - Down-regulation of several key actin-binding proteins, such as alpha-actinin,
      vinculin, gelsolin, and tropomyosins (TMs), is considered to contribute to the
      disorganized cytoskeleton present in many neoplastic cells. TMs stabilize actin
      filaments against the gel severing actions of proteins such as cofilin. Among
      multiple TMs expressed in non-muscle cells, tropomyosin-1 (TM1) isoform induces
      stress fibers and functions as a suppressor of malignant transformation. However,
      the molecular mechanisms of TM1-mediated cytoskeletal effects and tumor
      suppression remain poorly understood. We have hypothesized that the ability of
      TM1 to stabilize microfilaments is crucial for tumor suppression. In this study,
      by employing a variant TM1, which contains an N-terminal hemagglutinin epitope
      tag, we demonstrate that the N terminus is a key determinant of tropomyosin-1
      function. Unlike the wild type TM1, the modified protein fails to restore stress
      fibers and inhibit anchorage-independent growth in transformed cells.
      Furthermore, the N-terminal modification of TM1 disorganizes the cytoskeleton and
      delays cytokinesis in normal cells, abolishes binding to F-actin, and disrupts
      the dimeric associations in vivo. The functionally defective TM1 allows the
      association of cofilin to stress fibers and disorganizes the microfilaments,
      whereas wild type TM1 appears to restrict the binding of cofilin to stress
      fibers. TM1-induced cytoskeletal reorganization appears to be mediated through
      preventing cofilin interaction with microfilaments. Our studies provide in vivo
      functional evidence that the N terminus is a critical determinant of TM1
      functions, which in turn determines the organization of stress fibers.

PMID- 14722124
TI  - Impaired regulatory volume decrease in freshly isolated cholangiocytes from
      cystic fibrosis mice: implications for cystic fibrosis transmembrane conductance
      regulator effect on potassium conductance.
AB  - Various K(+) and Cl(-) channels are important in cell volume regulation and
      biliary secretion, but the specific role of cystic fibrosis transmembrane
      conductance regulator in cholangiocyte cell volume regulation is not known. The
      goal of this research was to study regulatory volume decrease (RVD) in bile duct
      cell clusters (BDCCs) from normal and cystic fibrosis (CF) mouse livers. Mouse
      BDCCs without an enclosed lumen were prepared as described (Cho, W. K. (2002) Am.
      J. Physiol. 283, G1320-G1327). The isotonic solution consisted of HEPES buffer
      with 40% of the NaCl replaced with isomolar amounts of sucrose, whereas hypotonic
      solution was the same as isotonic solution without sucrose. The cell volume
      changes were indirectly assessed by measuring cross-sectional area (CSA) changes
      of the BDCCs using quantitative videomicroscopy. Exposure to hypotonic solutions
      increased relative CSAs of normal BDCCs to 1.20 +/- 0.01 (mean +/- S.E., n = 50)
      in 10 min, followed by RVD to 1.07 +/- 0.01 by 40 min. Hypotonic challenge in CF
      mouse BDCCs also increased relative CSA to 1.20 +/- 0.01 (n = 53) in 10 min but
      without significant recovery. Coadministration of the K(+)-selective ionophore
      valinomycin restored RVD in CF mouse BDCCs, suggesting that the impaired RVD was
      likely from a defect in K(+) conductance. Moreover, this valinomycin-induced RVD
      in CF mice was inhibited by 5-nitro-2'-(3-phenylpropylamino)-benzoate, indicating
      that it is not from nonspecific effects. Neither cAMP nor calcium agonists could
      reverse the impaired RVD seen in CF cholangiocytes. Our conclusion is that CF
      mouse cholangiocytes have defective RVD from an impaired K(+) efflux pathway,
      which could not be reversed by cAMP nor calcium agonists.

PMID- 14722125
TI  - Identification of a novel conserved motif in the STAT family that is required for
      tyrosine phosphorylation.
AB  - The rapid transcriptional activation of cellular genes by either type 1
      interferons (IFNalpha/beta) or type 2 interferon (IFNgamma) is responsible for
      many of the pleiotropic effects of these cytokines, including their antiviral,
      antigrowth, and immunomodulatory activities. Interferon-stimulated gene
      expression is mediated by transcription factors termed Stats, which upon being
      tyrosine-phosphorylated, translocate to the nucleus and bind enhancers of
      interferon-activated genes. We have recently characterized a new Jurkat cell
      variant, named H123, where IFNalpha stimulates programmed cell death. H123 clones
      that are resistant to the apoptotic actions of IFNalpha have been selected. One
      of these clones (Clone 8) is defective in its responses to IFNalpha with regard
      to activation of genes that require tyrosine phosphorylation of Stat2.
      Stimulation of Clone 8 cells with IFNalpha induces normal tyrosine
      phosphorylation of Stat1 and Stat3. Sequencing of Stat2 RNA reveals a
      substitution of proline 630 located within the Src homology 2 domain of Stat2 to
      leucine (P630L). Pro-630 and its adjacent amino acids are conserved in all Stat
      family members but are absent in other proteins that contain Src homology 2
      domains. Expression of Stat2 P630L in cells inhibits IFNalpha-stimulated gene
      expression. These results not only define a critical motif in Stat2 required for
      its transcriptional activity, but they also provide evidence that resistance to
      type one IFNs can be mediated by mutations in Stat2 as well as those previously
      described for Stat1.

PMID- 14722126
TI  - Characterization of the Drosophila sphingosine kinases and requirement for Sk2 in
      normal reproductive function.
AB  - Sphingosine kinase is a highly conserved enzyme that catalyzes the synthesis of
      sphingosine 1-phosphate and reduces cellular levels of sphingosine and ceramide.
      Although ceramide is pro-apoptotic and sphingosine is generally growth
      inhibitory, sphingosine 1-phosphate signaling promotes cell proliferation,
      survival, and migration. Sphingosine kinase is thus in a strategic position to
      regulate important cell fate decisions which may contribute to normal animal
      development. To facilitate studies examining the potential role of sphingosine
      kinase and long chain base metabolism in Drosophila development, we characterized
      two putative Drosophila sphingosine kinase genes, Sk1 and Sk2. Both genes
      functionally and biochemically complement a yeast sphingosine kinase mutant,
      express predominantly cytosolic activities, and are capable of phosphorylating a
      range of endogenous and non-endogenous sphingoid base substrates. The two genes
      demonstrate overlapping but distinct temporal and spatial expression patterns in
      the Drosophila embryo, and timing of expression is consistent with observed
      changes in long chain base levels throughout development. A null Sk2 transposon
      insertion mutant demonstrated elevated long chain base levels, impaired flight
      performance, and diminished ovulation. This is the first reported mutation of a
      sphingosine kinase in an animal model; the associated phenotypes indicate that
      Sk1 and Sk2 are not redundant in biological function and that sphingosine kinase
      is essential for diverse physiological functions in this organism.

PMID- 14722128
TI  - Poised to challenge need for sleep, "wakefulness enhancer" rouses concerns.

PMID- 14722127
TI  - SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC
      1 recruitment to suppress hepatic gluconeogenic genes.
AB  - The hepatocyte nuclear factor-4alpha (HNF-4alpha)/PGC-1 pathway plays a crucial
      role in the transcriptional regulation of hepatic gluconeogenic enzymes such as
      phosphoenolpyruvate carboxykinase (PEPCK) and Glc-6-Pase, genes that are
      activated at fasting and suppressed in a fed state. SREBP-1c dominates the
      nutritional regulation of lipogenic genes inverse to gluconeogenesis. Here we
      show the mechanism by which SREBP-1 suppresses expression of gluconeogenic genes.
      A series of luciferase reporter assays demonstrated that SREBP-1a and -1c
      effectively inhibited the PEPCK promoter activity that was induced by HNF-4alpha.
      The HNF-4alpha-binding site in the glucocorticoid-response unit was responsible
      for the SREBP-1 inhibition, although SREBP-1 did not bind to the PEPCK promoter
      as demonstrated by electrophoretic mobility shift assays. The inhibitory effect
      was more potent in the isoform of SREBP-1a than SREBP-1c and was eliminated by
      deletion of the amino-terminal transactivation domain of SREBP-1.
      Coimmunoprecipitation experiments demonstrated that these two transcription
      factors directly interact through the transactivation domain of SREBP-1 and the
      ligand binding/AF2 domains of HNF-4alpha. Estimation of coactivator recruitment
      using HNF-4alpha-Gal4DBD fusion assay showed that SREBP-1 competitively inhibited
      PGC-1 recruitment, a requirement for HNF-4alpha activation. Consistent with these
      results, hepatic PEPCK and Glc-6-Pase mRNA levels are suppressed by
      overexpression of SREBP-1a and -1c in the transgenic mice. Our data indicate that
      SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a
      cross-talk with HNF-4alpha interference with PGC-1 recruitment.

PMID- 14722129
TI  - Markers in prenatal ultrasound debated.

PMID- 14722130
TI  - FDA warns on mercury in tuna.

PMID- 14722135
TI  - Association between thimerosal-containing vaccine and autism.

PMID- 14722136
TI  - Association between thimerosal-containing vaccine and autism.

PMID- 14722137
TI  - Treatment of sarin exposure.

PMID- 14722138
TI  - Treatment of sarin exposure.

PMID- 14722139
TI  - Treatment of sarin exposure.

PMID- 14722140
TI  - Level of exercise and risk of cardiovascular disease.

PMID- 14722141
TI  - Genital lesions of primary syphilis.

PMID- 14722142
TI  - Evaluation of drug utilization review programs.

PMID- 14722143
TI  - Evaluation of drug utilization review programs.

PMID- 14722144
TI  - Helicobacter pylori eradication to prevent gastric cancer in a high-risk region
      of China: a randomized controlled trial.
AB  - CONTEXT: Although chronic Helicobacter pylori infection is associated with
      gastric cancer, the effect of H pylori treatment on prevention of gastric cancer
      development in chronic carriers is unknown. OBJECTIVE: To determine whether
      treatment of H pylori infection reduces the incidence of gastric cancer. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective, randomized, placebo-controlled,
      population-based primary prevention study of 1630 healthy carriers of H pylori
      infection from Fujian Province, China, recruited in July 1994 and followed up
      until January 2002. A total of 988 participants did not have precancerous lesions
      (gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry.
      INTERVENTION: Patients were randomly assigned to receive H pylori eradication
      treatment: a 2-week course of omeprazole, 20 mg, a combination product of
      amoxicillin and clavulanate potassium, 750 mg, and metronidazole, 400 mg, all
      twice daily (n = 817); or placebo (n = 813). MAIN OUTCOME MEASURES: The primary
      outcome measure was incidence of gastric cancer during follow-up, compared
      between H pylori eradication and placebo groups. The secondary outcome measure
      was incidence of gastric cancer in patients with or without precancerous lesions,
      compared between the 2 groups. RESULTS: Among the 18 new cases of gastric cancers
      that developed, no overall reduction was observed in participants who received H
      pylori eradication treatment (n = 7) compared with those who did not (n = 11) (P
      =.33). In a subgroup of patients with no precancerous lesions on presentation, no
      patient developed gastric cancer during a follow-up of 7.5 years after H pylori
      eradication treatment compared with those who received placebo (0 vs 6; P =.02).
      Smoking (hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.3-16.5; P<.001)
      and older age (HR, 1.10; 95% CI, 1.05-1.15; P<.001) were independent risk factors
      for the development of gastric cancer in this cohort. CONCLUSIONS: We found that
      the incidence of gastric cancer development at the population level was similar
      between participants receiving H pylori eradication treatment and those receiving
      placebo during a period of 7.5 years in a high-risk region of China. In the
      subgroup of H pylori carriers without precancerous lesions, eradication of H
      pylori significantly decreased the development of gastric cancer. Further studies
      to investigate the role of H pylori eradication in participants with precancerous
      lesions are warranted.

PMID- 14722145
TI  - Procedural volume as a marker of quality for CABG surgery.
AB  - CONTEXT: There have been recent calls for using hospital procedural volume as a
      quality indicator for coronary artery bypass graft (CABG) surgery, but further
      research into analysis and policy implication is needed before hospital
      procedural volume is accepted as a standard quality metric. OBJECTIVE: To examine
      the contemporary association between hospital CABG procedure volume and outcome
      in a large national clinical database. DESIGN, SETTING, AND PARTICIPANTS:
      Observational analysis of 267 089 isolated CABG procedures performed at 439 US
      hospitals participating in the Society of Thoracic Surgeons National Cardiac
      Database between January 1, 2000, and December 31, 2001. MAIN OUTCOME MEASURE:
      Association between hospital CABG procedural volume and all-cause operative
      mortality (in-hospital or 30-day, whichever was longer). RESULTS: The median
      (interquartile range) annual hospital-isolated CABG volume was 253 (165-417)
      procedures, with 82% of centers performing fewer than 500 procedures per year.
      The overall operative mortality was 2.66%. After adjusting for patient risk and
      clustering effects, rates of operative mortality decreased with increasing
      hospital CABG volume (0.07% for every 100 additional CABG procedures; adjusted
      odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P =.004). While
      the association between volume and outcome was statistically significant overall,
      this association was not observed in patients younger than 65 years or in those
      at low operative risk and was confounded by surgeon volume. The ability of
      hospital volume to discriminate those centers with significantly better or worse
      mortality was limited due to the wide variability in risk-adjusted mortality
      among hospitals with similar volume. Closure of up to 100 of the lowest-volume
      centers (ie, those performing < or =150 CABG procedures/year) was estimated to
      avert fewer than 50 of 7110 (<1% of total) CABG-related deaths. CONCLUSION: In
      contemporary practice, hospital procedural volume is only modestly associated
      with CABG outcomes and therefore may not be an adequate quality metric for CABG
      surgery.

PMID- 14722146
TI  - Indirect vs direct hospital quality indicators for very low-birth-weight infants.
AB  - CONTEXT: Evidence-based selective referral strategies are being used by an
      increasing number of insurers to ensure that medical care is provided by high
      quality providers. In the absence of direct-quality measures based on patient
      outcomes, the standards currently in place for many conditions rely on indirect
      quality measures such as patient volume. OBJECTIVES: To assess the potential
      usefulness of volume as a quality indicator for very low-birth-weight (VLBW)
      infants and compare volume with other potential indicators based on readily
      available hospital characteristics and patient outcomes. DESIGN, SETTING, AND
      PARTICIPANTS: A retrospective study of 94 110 VLBW infants weighing 501 to 1500 g
      born in 332 Vermont Oxford Network hospitals with neonatal intensive care units
      between January 1, 1995, and December 31, 2000. MAIN OUTCOME MEASURES: Mortality
      among VLBW infants prior to discharge home; detailed case-mix adjustment was
      performed by using patient characteristics available immediately after birth.
      RESULTS: In hospitals with less than 50 annual admissions of VLBW infants, an
      additional 10 admissions were associated with an 11% reduction in mortality (95%
      confidence interval [CI], 5%-16%; P<.001). The annual volume of admissions only
      explained 9% of the variation across hospitals in mortality rates, and other
      readily available hospital characteristics explained an additional 7%. Historical
      volume was not significantly related to mortality rates in 1999-2000, implying
      that volume cannot prospectively identify high-quality providers. In contrast,
      hospitals in the lowest mortality quintile between 1995 and 1998 were found to
      have significantly lower mortality rates in 1999-2000 (odds ratio [OR], 0.64; 95%
      CI, 0.55-0.76; P<.001) and hospitals in the highest mortality quintile between
      1995 and 1998 had significantly higher mortality rates in 1999-2000 (OR, 1.37;
      95% CI, 1.16-1.64; P<.001). The percentage of hospital-level variation in
      mortality in 1999-2000 that was forecasted by the highest and lowest quintiles
      based on patient mortality was 34% compared with only 1% for the highest and
      lowest quintiles of volume. CONCLUSIONS: Referral of VLBW infants based on
      indirect-quality indicators such as patient volume may be minimally effective.
      Direct measures based on patient outcomes are more useful quality indicators for
      the purposes of selective referral, as they are better predictors of future
      mortality rates among providers and could save more lives.

PMID- 14722147
TI  - Coronary artery calcium score combined with Framingham score for risk prediction
      in asymptomatic individuals.
AB  - CONTEXT: Guidelines advise that all adults undergo coronary heart disease (CHD)
      risk assessment to guide preventive treatment intensity. Although the Framingham
      Risk Score (FRS) is often recommended for this, it has been suggested that risk
      assessment may be improved by additional tests such as coronary artery calcium
      scoring (CACS). OBJECTIVES: To determine whether CACS assessment combined with
      FRS in asymptomatic adults provides prognostic information superior to either
      method alone and whether the combined approach can more accurately guide primary
      preventive strategies in patients with CHD risk factors. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective observational population-based study, of 1461
      asymptomatic adults with coronary risk factors. Participants with at least 1
      coronary risk factor (>45 years) underwent computed tomography (CT) examination,
      were screened between 1990-1992, were contacted yearly for up to 8.5 years after
      CT scan, and were assessed for CHD. This analysis included 1312 participants with
      CACS results; excluded were 269 participants with diabetes and 14 participants
      with either missing data or had a coronary event before CACS was performed. MAIN
      OUTCOME MEASURE: Nonfatal myocardial infarction (MI) or CHD death. RESULTS:
      During a median of 7.0 years of follow-up, 84 patients experienced MI or CHD
      death; 70 patients died of any cause. There were 291 (28%) participants with an
      FRS of more than 20% and 221 (21%) with a CACS of more than 300. Compared with an
      FRS of less than 10%, an FRS of more than 20% predicted the risk of MI or CHD
      death (hazard ratio [HR], 14.3; 95% confidence interval [CI]; 2.0-104; P =.009).
      Compared with a CACS of zero, a CACS of more than 300 was predictive (HR, 3.9;
      95% CI, 2.1-7.3; P<.001). Across categories of FRS, CACS was predictive of risk
      among patients with an FRS higher than 10% (P<.001) but not with an FRS less than
      10%. CONCLUSION: These data support the hypothesis that high CACS can modify
      predicted risk obtained from FRS alone, especially among patients in the
      intermediate-risk category in whom clinical decision making is most uncertain.

PMID- 14722148
TI  - Electrocardiographic and hemodynamic effects of a multicomponent dietary
      supplement containing ephedra and caffeine: a randomized controlled trial.
AB  - CONTEXT: Metabolife 356, a multicomponent dietary supplement containing ephedra
      and caffeine (DSEC) in addition to several other components, is the top-selling
      dietary weight loss supplement. Given its common use, anecdotal reports of
      cardiovascular and cerebrovascular adverse events, and paucity of safety data,
      further research with this DSEC was warranted. OBJECTIVE: To determine the impact
      of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure
      (SBP). DESIGN: Randomized, double-blind, placebo-controlled, crossover study
      conducted from January to May 2003. SETTING AND PARTICIPANTS: Fifteen healthy
      volunteers (mean [SD] age, 26.7 [2.52] years; weight, 72.7 [14.93] kg), 6 (40%)
      of whom were women, recruited from the University of Connecticut, Storrs campus.
      INTERVENTION: A single dose of the DSEC (containing 19 ingredients including
      ephedra [12 mg] and caffeine [40 mg]) or matching placebo were administered in a
      crossover fashion with a 7-day washout period between treatments. MAIN OUTCOME
      MEASURES: Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing
      for the DSEC relative to placebo. RESULTS: Individuals receiving the DSEC had a
      longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7]
      milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62]
      mm Hg; P =.009) compared with placebo. Participants who received the DSEC were
      more likely to experience a QTc interval increase of at least 30 milliseconds vs
      placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95%
      confidence interval, 1.40-5.10]). There were no significant sex-related
      differences. CONCLUSIONS: The ephedra- and caffeine-containing dietary supplement
      Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual
      ingredient or ingredients in Metabolife 356 responsible for these findings are
      not known, patients should be instructed to avoid this and similar dietary
      supplements until more information is known about their safety.

PMID- 14722149
TI  - Transmission and clinical features of enterovirus 71 infections in household
      contacts in Taiwan.
AB  - CONTEXT: Although enterovirus 71 has caused epidemics associated with significant
      morbidity and mortality, its transmission has not been thoroughly investigated.
      OBJECTIVES: To investigate enterovirus 71 transmission and determine clinical
      outcomes within households. DESIGN, SETTING, AND PARTICIPANTS: Prospective family
      cohort study to investigate patients at a children's hospital in Taiwan and
      family members of these patients who had signs and symptoms suggestive of
      enterovirus 71 between February 2001 and August 2002. Patients and household
      members underwent clinical evaluations, virological studies, questionnaire-based
      interviews, and were followed up for 6 months. MAIN OUTCOME MEASURES: Enterovirus
      71 infection, defined as a positive viral culture from a throat or rectal swab,
      or the presence of IgM or a 4-fold increase in neutralizing antibody in serum;
      and clinical syndromes, defined as asymptomatic; uncomplicated symptomatic; and
      complicated; with unfavorable outcomes of sequelae or death. RESULTS: Ninety-four
      families (433 family members) had at least 1 family member with evidence of
      enterovirus 71 infection. The overall enterovirus 71 transmission rate to
      household contacts was 52% (176/339 household contacts). Transmission rates were
      84% for siblings (70/83); 83%, cousins (19/23); 41%, parents (72/175); 28%,
      grandparents (10/36); and 26%, uncles and aunts (5/19). Of 183 infected children,
      11 (6%) were asymptomatic and 133 (73%) had uncomplicated illnesses (hand, foot,
      and mouth disease, herpangina, nonspecific febrile illness, upper respiratory
      tract infection, enteritis, or viral exanthema). Twenty-one percent (39/183)
      experienced complicated syndromes including the central nervous system or
      cardiopulmonary failure. During the 6-month follow-up, 10 died and 13 had long
      term sequelae consisting of dysfunction in swallowing, cranial nerve palsies,
      central hypoventilation, or limb weakness and atrophy. Age younger than 3 years
      was the most significant factor associated with an unfavorable outcome in
      children (P =.004). Among 87 infected adults, 46 (53%) were asymptomatic, 34
      (39%) had nonspecific illnesses of fever, sore throat, or gastrointestinal
      discomfort, and 7 (8%) had hand, foot, and mouth disease. There were no
      complicated cases in adults. CONCLUSIONS: Enterovirus 71 household transmission
      rates were high for children in Taiwan and severe disease with serious
      complications, sequelae, and death occurred frequently. In contrast, adults had a
      much lower rate of acquisition of the infection and much less adverse sequelae.

PMID- 14722150
TI  - Subclinical thyroid disease: scientific review and guidelines for diagnosis and
      management.
AB  - CONTEXT: Patients with serum thyroid-stimulating hormone (TSH) levels outside the
      reference range and levels of free thyroxine (FT4) and triiodothyronine (T3)
      within the reference range are common in clinical practice. The necessity for
      further evaluation, possible treatment, and the urgency of treatment have not
      been clearly established. OBJECTIVES: To define subclinical thyroid disease,
      review its epidemiology, recommend an appropriate evaluation, explore the risks
      and benefits of treatment and consequences of nontreatment, and determine whether
      population-based screening is warranted. DATA SOURCES: MEDLINE, EMBASE, Biosis,
      the Agency for Healthcare Research and Quality, National Guideline Clearing
      House, the Cochrane Database of Systematic Reviews and Controlled Trials
      Register, and several National Health Services (UK) databases were searched for
      articles on subclinical thyroid disease published between 1995 and 2002. Articles
      published before 1995 were recommended by expert consultants. STUDY SELECTION AND
      DATA EXTRACTION: A total of 195 English-language or translated papers were
      reviewed. Editorials, individual case studies, studies enrolling fewer than 10
      patients, and nonsystematic reviews were excluded. Information related to
      authorship, year of publication, number of subjects, study design, and results
      were extracted and formed the basis for an evidence report, consisting of tables
      and summaries of each subject area. DATA SYNTHESIS: The strength of the evidence
      that untreated subclinical thyroid disease is associated with clinical symptoms
      and adverse clinical outcomes was assessed and recommendations for clinical
      practice developed. Data relating the progression of subclinical to overt
      hypothyroidism were rated as good, but data relating treatment to prevention of
      progression were inadequate to determine a treatment benefit. Data relating a
      serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were
      rated as fair but data relating to benefits of treatment were rated as
      insufficient. All other associations of symptoms and benefit of treatment were
      rated as insufficient or absent. Data relating a serum TSH concentration lower
      than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt
      hyperthyroidism were rated as good, but no data supported treatment to prevent
      these outcomes. Data relating restoration of the TSH level to within the
      reference range with improvements in bone mineral density were rated as fair.
      Data addressing all other associations of subclinical hyperthyroid disease and
      adverse clinical outcomes or treatment benefits were rated as insufficient or
      absent. Subclinical hypothyroid disease in pregnancy is a special case and
      aggressive case finding and treatment in pregnant women can be justified.
      CONCLUSIONS: Data supporting associations of subclinical thyroid disease with
      symptoms or adverse clinical outcomes or benefits of treatment are few. The
      consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0
      mIU/L) are minimal and we recommend against routine treatment of patients with
      TSH levels in these ranges. There is insufficient evidence to support population
      based screening. Aggressive case finding is appropriate in pregnant women, women
      older than 60 years, and others at high risk for thyroid dysfunction.

PMID- 14722151
TI  - Subclinical thyroid disease: clinical applications.
AB  - Subclinical hypothyroidism and hyperthyroidism are diagnoses based on laboratory
      evaluation with few if any clinical signs or symptoms. Subclinical hypothyroidism
      is defined as an elevation in serum thyroid-stimulating hormone (TSH) above the
      upper limit of the reference range (0.45-4.5 mIU/L) with normal serum FT4
      concentration; subclinical hyperthyroidism is defined as a decrease in serum TSH
      below the reference range with normal serum FT4 and T3 concentrations. Though
      these conditions represent the earliest stages of thyroid dysfunction, the
      benefits of detecting and treating subclinical thyroid disease are not well
      established. Most persons found to have subclinical thyroid disease will have TSH
      values between 0.1 and 0.45 mIU/L or between 4.5 and 10 mIU/L, for which the
      benefits of treatment are not clearly established; treatment may be beneficial in
      individuals with serum TSH lower than 0.1 mIU/L or higher than 10 mIU/L. This
      article illustrates approaches to managing patients with subclinical
      hypothyroidism and hyperthyroidism through 5 case scenarios that apply the
      principles of evidence-based medicine. Because of the substantial uncertainty
      concerning the consequences of untreated subclinical hypothyroidism and
      hyperthyroidism, as well as the benefit of initiating treatment, patient
      preferences are important in deciding on management of subclinical disease.

PMID- 14722152
TI  - Helicobacter pylori infection and gastric cancer--for want of more outcomes.

PMID- 14722153
TI  - Improving cardiac surgery quality--volume, outcome, process?

PMID- 14722154
TI  - JAMA patient page. Stomach cancer.

PMID- 14722155
TI  - Genetics of cleft lip and palate: syndromic genes contribute to the incidence of
      non-syndromic clefts.
AB  - Clefts of the lip and/or palate (CL/P) are among the most common birth defects
      worldwide. The majority are non-syndromic where CL/P occurs in isolation of other
      phenotypes. Where one or more additional features are involved, clefts are
      referred to as syndromic. Collectively CL/P has a major clinical impact requiring
      surgical, dental, orthodontic, speech, hearing and psychological treatments or
      therapies throughout childhood. The etiology of CL/P is complex and thought to
      involve both major and minor genetic influences with variable interactions from
      environmental factors. Using a combination of gene targeting technology and
      traditional developmental techniques in both mouse and chick, significant
      progress has been made in the identification of numerous genes and gene pathways
      critical for craniofacial development. Despite this, it has been a particular
      source of frustration that mutation screening of specific candidates, association
      studies and even genome-wide scans have largely failed to reveal the molecular
      basis of human clefting. Nevertheless, some important findings have recently come
      from studies involving syndromic forms of the disorder. These include several
      genes which have now been shown to contribute a major effect on the etiology of
      CL/P. Furthermore, these genes can also be used to demonstrate a significant
      overlap between syndromic and non-syndromic CL/P. The study of these syndromic
      genes and their molecular pathways will provide a useful and informative route
      with which to gain a better understanding of human craniofacial pathology.

PMID- 14722156
TI  - Redistribution of transcription start sites within the FMR1 promoter region with
      expansion of the downstream CGG-repeat element.
AB  - Fragile X syndrome, the most common form of mental impairment, is caused by
      expansion of a (CGG)n trinucleotide repeat element located in the 5' untranslated
      region of the fragile X mental retardation 1 (FMR1) gene. Repeat expansion is
      known to influence both transcription and translation; however, the mechanisms by
      which the CGG element exerts its effects are not known. In the current work, we
      have utilized 5'-RLM-RACE to examine the influence of CGG repeat number on the
      utilization of transcription start sites in normal (n<55) and premutation
      (54<n<200) cell lines of both non-neural (lymphoblastoid) and neural (primary
      astrocyte) origin. Our results demonstrate that, in both neural and non-neural
      cells, transcription of the FMR1 gene is initiated from several transcription
      start sites within a approximately 50 nt region that lies approximately 130 nt
      upstream of the CGG repeat element. For normal alleles, most transcripts initiate
      from the downstream-most start site, close to the single position identified
      previously. Surprisingly, as the size of the CGG repeat expands into the
      premutation range, initiation shifts to the upstream sites, suggesting that the
      CGG element may act as a downstream enhancer/modulator of transcription. The
      shift in start site selection for both neural and non-neural cells indicates that
      the effect is general. Furthermore, the correspondence between start site
      utilization and the degree of elevation of FMR1 mRNA suggests that a substantial
      fraction of the increased message in the premutation range may derive from the
      upstream start sites.

PMID- 14722157
TI  - A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein
      localizes to the splicing factor compartment.
AB  - Beta-amyloid precursor protein (APP) is implicated in the pathobiology of
      Alzheimer's disease (AD). To gain insight into its function, we have investigated
      the proteolytic processing and post-translational modification of APP in relation
      to its intracellular traffic and localization. The proteolytic processing that
      generates the amyloid beta-peptide (Abeta) also releases into the cytoplasm the
      carboxy-terminal fragment of APP, Cgamma. Using the catecholaminergic cell line,
      CAD, and an antibody to a form of APP that is phosphorylated at Thr668 (pAPP;
      numbering for APP695), we show that a phosphorylated, carboxy-terminal fragment
      of APP, probably Cgamma, is present in the nucleus, where it localizes to
      subnuclear particles. The labeling with anti-pAPP antibody co-localizes with
      proteins that define the splicing factor compartment (SFC) [e.g. the small
      nuclear ribonucleoprotein (snRNP), U2B, and serine/arginine-rich (SR) proteins],
      but is excluded from the coiled bodies and the gems. This distribution of pAPP
      epitopes was found in CAD cells independent of their state of differentiation, as
      well as in primary cortical neurons, epithelial cells and fibroblasts. We further
      show that exogenously expressed Cgamma becomes phosphorylated, and distributes
      throughout the cell. A fraction of this Cgamma is translocated into the nucleus,
      where it co-localizes with endogenous pAPP epitopes. Finally, we show that the
      APP binding, scaffolding protein, Fe65 co-localizes with pAPP epitopes and with
      expressed Cgamma at intranuclear speckles. These results suggest that
      phosphorylated Cgamma accumulates at the SFC. Thus, APP may play a role in pre
      mRNA splicing, and Fe65 and APP phosphorylation may regulate this function.

PMID- 14722158
TI  - Adaptive evolution of ASPM, a major determinant of cerebral cortical size in
      humans.
AB  - A prominent trend in the evolution of humans is the progressive enlargement of
      the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated)
      gene has the potential to play a role in this evolutionary process, because
      mutations in this gene cause severe reductions in the cerebral cortical size of
      affected humans. Here, we show that the evolution of ASPM is significantly
      accelerated in great apes, especially along the ape lineages leading to humans.
      Additionally, the lineage from the last human/chimpanzee ancestor to humans shows
      an excess of non-synonymous over synonymous substitutions, which is a signature
      of positive Darwinian selection. A comparison of polymorphism and divergence
      using the McDonald-Kreitman test confirms that ASPM has indeed experienced
      intense positive selection during recent human evolution. This test also reveals
      that, on average, ASPM fixed one advantageous amino acid change in every 300,000
      400,000 years since the human lineage diverged from chimpanzees some 5-6 million
      years ago. We therefore conclude that ASPM underwent strong adaptive evolution in
      the descent of Homo sapiens, which is consistent with its putative role in the
      evolutionary enlargement of the human brain.

PMID- 14722159
TI  - Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats.
AB  - Myotonic dystrophy (DM) type 1 is caused by an expansion of a CTG repeat in the
      DMPK gene and type 2 by a CCTG repeat in the ZNF9 gene. Previous reports have
      suggested that transcripts containing expanded CUG/CCUG repeats might have toxic
      gain-of-function effects, probably affecting the function of RNA-binding proteins
      in the pathogenesis of DM. Here, it was attempted to compare the RNA-binding
      properties of three proteins, CUG-BP, MBNL1/EXP and PKR, which have previously
      been suggested to interact with CUG repeats. MBNL1, but not CUG-BP or PKR,
      interacted with both CUG and CCUG repeats in a yeast three-hybrid system. By
      using various synthetic RNAs, it was found that MBNL1 specifically interacts with
      repetitive sequences summarized as CHHG and CHG repeats, where H is A, U or C.
      Interestingly, MBNL1 did not interact with a genuine double-stranded RNA
      comprising CAG/CUG repeats, suggesting that MBNL1 prefers bulge-containing double
      stranded RNAs. Deletion analysis indicates a difference in RNA-binding abilities
      among splice variants of MBNL1. It was also found that MBNL1 can bind to
      repetitive motifs in ZNF9, which contain a minimal length of CCUG repeats with
      non-CCUG insertions.

PMID- 14722160
TI  - Progress in defining the molecular basis of type 2 diabetes mellitus through
      susceptibility-gene identification.
AB  - The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major
      challenge for health care delivery worldwide. Identification of genes influencing
      individual susceptibility to disease offers a route to better understanding of
      the molecular mechanisms underlying pathogenesis, a necessary prerequisite for
      the rational development of improved preventative and therapeutic methods. The
      past decade has seen substantial success in identifying genes responsible for
      monogenic forms of diabetes (notably, maturity-onset diabetes of the young), and,
      in patients presenting with early-onset diabetes, a precise molecular diagnosis
      is an increasingly important element of optimal clinical care. Progress in gene
      identification for more common, multifactorial forms of type 2 diabetes has been
      slower, but there is now compelling evidence that common variants in the PPARG,
      KCNJ11 and CAPN10 genes influence T2D-susceptibility, and positional cloning
      efforts within replicated regions of linkage promise to deliver additional
      components of inherited susceptibility. The challenge in the years to come will
      be to understand how T2D risk is influenced by the interaction of these variants
      with each other and with pertinent environmental factors encountered during
      gestation, childhood and adulthood; and to establish how best to apply this
      understanding to provide individuals with clinically-useful diagnostic,
      prognostic and therapeutic information.

PMID- 14722161
TI  - Entropy is blind to nitrous oxide. Can we see why?

PMID- 14722162
TI  - Gone but not forgotten-or was it?

PMID- 14722163
TI  - Surgical critical care: the Overnight Intensive Recovery (OIR) concept.

PMID- 14722164
TI  - Entropy of EEG during anaesthetic induction: a comparative study with propofol or
      nitrous oxide as sole agent.
AB  - BACKGROUND: The search continues for an anaesthetic monitor that can define the
      level of anaesthesia in an individual patient irrespective of anaesthetic
      agent(s) used. Studies of available monitors based on bispectral analysis or
      evoked auditory potentials show the complexity of the problem. We assessed a new
      monitor, based on the entropy of the EEG, during induction of anaesthesia with
      either propofol or nitrous oxide. METHODS: In an open, randomized study (two
      groups; n=10) of day surgical patients, we induced loss of response with
      incremental boluses of propofol. The other group was given propofol 30 mg and
      then increasing concentrations of nitrous oxide until loss of response. We
      measured entropy with the M-Entropy Module S/5 (Datex-Ohmeda) using forehead
      electrodes and recorded response entropy (RE; including frontal electromyogram)
      and state entropy (SE; only the cortical EEG). Values are median (range).
      RESULTS: Baseline values were RE 98 (96-100), SE 89 (87-91) and RE 98 (96-99), SE
      89 (87-91) for the propofol and nitrous oxide patients, respectively. During
      propofol induction, both entropy indices decreased with increasing sedation, with
      RE 40 (23-76) and SE 34 (17-70) at loss of response. Neither RE nor SE decreased
      during nitrous oxide inhalation, and at loss of response using nitrous oxide, RE
      and SE were unchanged at 98 (96-100) and 88 (85-91) respectively. CONCLUSIONS:
      The entropy monitor of anaesthetic depth shows a successive decrease with
      propofol but loss of consciousness with nitrous oxide is not associated with
      change in entropy indices.

PMID- 14722165
TI  - Unconscious learning during surgery with propofol anaesthesia.
AB  - BACKGROUND: Learning during anaesthesia has been demonstrated, but little is
      known about the circumstances under which it may occur. This study investigated
      the hypothesis that learning during anaesthesia occurs during, but not before,
      surgical stimulation. METHODS: Words were played through headphones to 64 day
      surgery patients during propofol anaesthesia. Fourteen words were played
      repeatedly (15 times) for 1 min each either before (n=32) or during (n=32)
      surgical stimulation. The depth of anaesthesia was estimated using the bispectral
      index (BIS). Heart rate, ventilatory frequency, mean arterial pressure, end-tidal
      carbon dioxide concentration, and infusion rate of propofol were recorded at 1
      min intervals during word presentation. On recovery, memory was assessed using an
      auditory word stem completion test and word recognition test. RESULTS: The mean
      BIS, arterial pressure, end-tidal carbon dioxide and heart rate during word
      presentation did not differ between the groups. The infusion rate of propofol and
      the ventilatory frequency were significantly greater in the during-surgical
      stimulation group. There was no evidence for explicit recall or recognition, nor
      of awareness during anaesthesia (median mean-BIS=38 in the before-surgical
      stimulation group and 42 in the during-surgical stimulation group). Only patients
      who were played words during surgical stimulation showed significant implicit
      memory on recovery (mean score=0.08, P<0.02) However, their scores were not
      significantly higher than those of the before-surgical stimulation group (mean
      score=0.01). CONCLUSIONS: Learning during anaesthesia seems more likely to occur
      during rather than before surgical stimulation at comparable anaesthetic depth.
      We hypothesize that surgical stimulation facilitates learning during anaesthesia,
      independently of its effects on anaesthetic depth.

PMID- 14722166
TI  - Comparison of structured use of routine laboratory tests or near-patient
      assessment with clinical judgement in the management of bleeding after cardiac
      surgery.
AB  - BACKGROUND: Using algorithms based on point of care coagulation tests can
      decrease blood loss and blood component transfusion after cardiac surgery. We
      wished to test the hypothesis that a management algorithm based on near-patient
      tests would reduce blood loss and blood component use after routine coronary
      artery surgery with cardiopulmonary bypass when compared with an algorithm based
      on routine laboratory assays or with clinical judgement. METHODS: Patients
      (n=102) undergoing elective coronary artery surgery with cardiac bypass were
      randomized into two groups. In the point of care group, the management algorithm
      was based on information provided by three devices, the Hepcon,
      thromboelastography and the PFA-100 platelet function analyser. Management in the
      laboratory test group depended on rapidly available laboratory clotting tests and
      transfusion of haemostatic blood components only if specific criteria were met.
      Blood loss and transfusion was compared between these two groups and with a
      retrospective case-control group (n=108), in which management of bleeding had
      been according to the clinician's discretion. RESULTS: All three groups had
      similar median blood losses. The transfusion of packed red blood cells (PRBCs)
      and blood components was greater in the clinician discretion group (P<0.05) but
      there was no difference in the transfusion of PRBCs and blood components between
      the two algorithm-guided groups. CONCLUSION: Following algorithms based on point
      of care tests or on structured clinical practice with standard laboratory tests
      does not decrease blood loss, but reduces the transfusion of PRBCs and blood
      components after routine cardiac surgery, when compared with clinician
      discretion. Cardiac surgery services should use transfusion guidelines based on
      laboratory-guided algorithms, and the possible benefits of point of care testing
      should be tested against this standard.

PMID- 14722167
TI  - Effect of remifentanil infusion rate on stress response to the pre-bypass phase
      of paediatric cardiac surgery.
AB  - BACKGROUND: Opioids are used routinely to eliminate the stress response in the
      pre-bypass phase of paediatric cardiac surgery. Remifentanil is a unique opioid
      allowing a rapidly titratable effect. No data are available regarding a suitable
      remifentanil dose regimen for obtunding stress and cardiovascular responses to
      such surgery. METHODS: We recruited 49 infants and children under 5 yr old who
      were randomized to receive one of four remifentanil infusion rates (0.25, 1.0,
      2.5, or 5.0 micro g kg(-1) min(-1)). Blood samples were obtained at induction,
      pre-surgery, 5 min after opening the chest, and immediately pre-bypass. Whole
      blood glucose was measured at all time points while cortisol and neuropeptide Y
      (NPY) were measured in the first and last samples. Heart rate and arterial
      pressure were also recorded. RESULTS: There was a significant increase in whole
      blood glucose 5 min after opening the chest and pre-bypass (P=0.009, P=0.002) in
      patients receiving remifentanil 0.25 micro g kg(-1) min(-1), but not in those
      receiving higher doses. Increased remifentanil dosage was associated with reduced
      plasma cortisol during surgery (P<0.001). Baseline NPY showed considerable
      variation and there was no association between pre-bypass NPY and remifentanil
      dose. There was a significantly higher heart rate at the pre-bypass stage of
      surgery in the remifentanil 0.25 micro g kg(-1) min(-1) group compared with
      higher doses (P=0.0006). Four out of five neonates with complex cardiac
      conditions showed severe bradycardia associated with remifentanil. CONCLUSIONS:
      In infants and children under 5 yr, remifentanil infusions of 1.0 micro g kg(-1)
      min(-1) and greater can suppress the glucose increase and tachycardia associated
      with the pre-bypass phase of cardiac surgery, while 0.25 micro g kg(-1) min(-1)
      does not. Remifentanil should be used with caution in neonates with complex
      congenital heart disease.

PMID- 14722168
TI  - Double lumen tube location predicts tube malposition and hypoxaemia during one
      lung ventilation.
AB  - BACKGROUND: Poor positioning of an endobronchial double lumen tube (DLT) could
      affect oxygenation during one lung ventilation (OLV). We set out to relate DLT
      position to hypoxaemia and DLT misplacement during OLV. METHODS: We recruited 152
      ASA physical status I-II patients about to have elective thoracic surgery. The
      trachea was intubated with a left-sided DLT. Tube position was assessed by fibre
      optic scope and correction was made after patient positioning and during OLV. If
      Pa(O(2)) was less than 10.7 kPa, the DLT position was checked and then PEEP,
      continuous positive airway pressure (CPAP), oxygen insufflation, or two lung
      ventilation (TLV) were tried. RESULTS: The DLT was found to be misplaced in 49
      patients (32%) after patient positioning, and in 38 patients (25%) during OLV.
      PEEP to the dependent lung, CPAP or apneic oxygen insufflation to the non
      dependent lung, or brief periods of TLV, were applied in 46 patients (30%).
      Patients who had DLT malposition after placing the patient in the lateral
      position had a greater incidence of DLT malposition during OLV (59 vs 9%) and
      also required each intervention more frequently (57 vs 10%). Patients with DLT
      malposition during OLV also required interventions more often (84 vs 12%).
      CONCLUSIONS: Patients who have DLT malposition after placing the patient in the
      lateral position had more DLT malposition during OLV and hypoxaemia during OLV.

PMID- 14722169
TI  - Effect of obesity and site of surgery on perioperative lung volumes.
AB  - BACKGROUND: Although obese patients are thought to be susceptible to
      postoperative pulmonary complications, there are only limited data on the
      relationship between obesity and lung volumes after surgery. We studied how
      surgery and obesity affect lung volumes measured by spirometry. METHODS: We
      prospectively studied 161 patients having either breast surgery (Group A, n=80)
      or lower abdominal laparotomy (Group B, n=81). Premedication and general
      anaesthesia were standardized. Spirometry was measured with the patient supine,
      in a 30 degrees head-up position. We measured vital capacity (VC), forced vital
      capacity, peak expiratory flow and forced expiratory volume in 1 s at
      preoperative assessment (baseline), after premedication (before induction of
      anaesthesia) and 10-20 min, 1 h and 3 h after extubation. RESULTS: Baseline
      spirometric values were all within the normal range. All perioperative values
      decreased significantly with increasing body mass index (BMI). The greatest
      reduction of mean VC (expressed as percentage of baseline values) occurred after
      extubation, and was more marked after laparotomy than after breast surgery (23
      (SD 14)% vs 20 (14)%). Considering patients according to BMI (<25, 25-30, >30),
      VC decreased after surgery by 12 (7)%, 24 (8)% and 40 (10)%, respectively. VC
      recovered more rapidly in Group A. CONCLUSION: Postoperative reduction in
      spirometric volumes was related to BMI. Obesity had more effect on VC than the
      site of surgery.

PMID- 14722170
TI  - Developmental pharmacokinetics of morphine and its metabolites in neonates,
      infants and young children.
AB  - BACKGROUND: Descriptions of the pharmacokinetics and metabolism of morphine and
      its metabolites in young children are scant. Previous studies have not
      differentiated the effects of size from those related to age during infancy.
      METHODS: Postoperative children 0-3 yr old were given an intravenous loading dose
      of morphine hydrochloride (100 micro g kg(-1) in 2 min) followed by either an
      intravenous morphine infusion of 10 micro g h(-1) kg(-1) (n=92) or 3-hourly
      intravenous morphine boluses of 30 micro g kg(-1) (n=92). Additional morphine (5
      micro g kg(-1)) every 10 min was given if the visual analogue (VAS, 0-10) pain
      score was >/=4. Arterial blood (1.4 ml) was sampled within 5 min of the loading
      dose and at 6, 12 and 24 h for morphine, morphine-3-glucuronide (M3G) and
      morphine-6-glucuronide (M6G). The disposition of morphine and formation
      clearances of morphine base to its glucuronide metabolites and their elimination
      clearances were estimated using non-linear mixed effects models. RESULTS: The
      analysis used 1856 concentration observations from 184 subjects. Population
      parameter estimates and their variability (%) for a one-compartment, first-order
      elimination model were as follows: volume of distribution 136 (59.3) litres,
      formation clearance to M3G 64.3 (58.8) litres h(-1), formation clearance to M6G
      3.63 (82.2) litres h(-1), morphine clearance by other routes 3.12 litres h(-1)
      per 70 kg, elimination clearance of M3G 17.4 (43.0) litres h(-1), elimination
      clearance of M6G 5.8 (73.8) litres h(-1). All parameters are standardized to a 70
      kg person using allometric 3/4 power models and reflect fully mature adult
      values. The volume of distribution increased exponentially with a maturation half
      life of 26 days from 83 litres per 70 kg at birth; formation clearance to M3G and
      M6G increased with a maturation half-life of 88.3 days from 10.8 and 0.61 litres
      h(-1) per 70 kg respectively at birth. Metabolite formation decreased with
      increased serum bilirubin concentration. Metabolite clearance increased with age
      (maturation half-life 129 days), and appeared to be similar to that described for
      glomerular filtration rate maturation in infants. CONCLUSION: M3G is the
      predominant metabolite of morphine in young children and total body morphine
      clearance is 80% that of adult values by 6 months. A mean steady-state serum
      concentration of 10 ng ml(-1) can be achieved in children after non-cardiac
      surgery in an intensive care unit with a morphine hydrochloride infusion of 5
      micro g h(-1) kg(-1) at birth (term neonates), 8.5 micro g h(-1) kg(-1) at 1
      month, 13.5 micro g h(-1) kg(-1) at 3 months and 18 micro g h(-1) kg(-1) at 1
      year and 16 micro g h(-1) kg(-1) for 1- to 3-yr-old children.

PMID- 14722171
TI  - Pharmacokinetics of levobupivacaine 0.25% following caudal administration in
      children under 2 years of age.
AB  - BACKGROUND: Levobupivacaine, the S(-)enantiomer of racemic bupivacaine is less
      cardiotoxic than racemic bupivacaine and the R(+)enantiomer dexbupivacaine, while
      retaining similar local anaesthetic properties and potency to racemic
      bupivacaine. The pharmacokinetic profiles of the two bupivacaine enantiomers
      differs and that of racemic bupivacaine may be age dependent. We examined the
      pharmacokinetics of levobupivacaine after its single shot caudal epidural
      administration in children. METHODS: An open-label phase 2 study was undertaken
      to examine the pharmacokinetics of levobupivacaine 0.25% 2 mg kg(-1) in 49
      children aged less than 2 yr, after single shot caudal epidural administration.
      Plasma concentrations were determined at intervals up to 60 min after caudal
      injection. RESULTS: Time to peak plasma concentration (T(max)) ranged between 5
      and 60 min (median 30 min) and was reached later in children aged less than 3
      months (P<0.005). Peak plasma concentration (C(max)) ranged between 0.41 and 2.12
      micro g ml(-1) (median 0.80, mean (SD) 0.91 (0.40) micro g ml(-1)). CONCLUSION:
      After the caudal epidural administration of levobupivacaine 2 mg kg(-1) in
      children less than 2 yr of age, C(max) was within the accepted safe range for
      racemic bupivacaine. T(max) varied and occurred later in some children,
      particularly those aged less than 3 months. Sampling in future pharmacokinetic
      studies in this age group should extend beyond 60 min.

PMID- 14722172
TI  - Caudal bupivacaine supplemented with caudal or intravenous clonidine in children
      undergoing hypospadias repair: a double-blind study.
AB  - BACKGROUND: Clonidine is used increasingly in paediatric anaesthetic practice to
      prolong the duration of action of caudal block with a local anaesthetic agent.
      Which route of administration of clonidine is the most beneficial remains
      unknown. We compared the effects of caudal and i.v. clonidine on postoperative
      analgesia produced by caudal bupivacaine after hypospadias repair. METHODS: Forty
      six children (ASA I or II) aged 24-104 months received standardized premedication
      with midazolam, a general anaesthetic and a caudal block with bupivacaine 0.25%,
      0.5 ml kg(-1). The children were randomized in a double-blind fashion to two
      groups: the i.v. group received clonidine 2 micro g kg(-1) i.v. and
      simultaneously the same volume of saline caudally. The caudal group received
      clonidine 2 micro g kg(-1) caudally and a similar volume of saline i.v. After
      surgery, all children received acetaminophen 20 mg kg(-1) rectally or orally 6
      hourly and were given a patient-controlled or nurse-controlled analgesia
      (PCA/NCA) pump with i.v. morphine (bolus of 25 micro g kg(-1) and an 8-min
      lockout period with no background infusion). Monitoring of scores for pain,
      sedation, motor block, and postoperative nausea and vomiting was performed by
      nurses blinded to the study allocations. Time to first activation of the PCA/NCA
      pump and 0-24 h and 24-48 h morphine consumption were also recorded. RESULTS:
      Forty-four children completed the study. Age, weight and duration of anaesthesia
      and surgery were similar in the two groups. The median (range) time to first
      activation of the PCA/NCA pump was similar in the two groups: 425 (150-1440) min
      in the i.v. group and 450 (130-1440) min in the caudal group. The number of
      children not requiring postoperative morphine was four and seven respectively.
      Morphine consumption during 0-24 h and 24-48 h was similar between groups.
      CONCLUSIONS: The analgesic effect of clonidine 2 micro g kg(-1) as an adjunct to
      caudal block with bupivacaine 0.25%, 0.5 ml kg(-1) is similar whether
      administered i.v. or caudally.

PMID- 14722173
TI  - Comparison of articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in
      cataract extraction.
AB  - BACKGROUND: Articaine is the most widely used local anaesthetic for dental
      anaesthesia in Germany, Italy and The Netherlands and has recently been
      introduced and licensed for dental use in the UK. We have previously shown
      articaine to be superior to a standard mixture of bupivacaine 0.5%/lidocaine 2%
      for peribulbar anaesthesia. Sub-Tenon's anaesthesia arguably provides a safer
      method of anaesthetic delivery for cataract surgery. A blunt cannula is used in
      this technique, thus greatly reducing the risk of globe perforation, intrathecal
      injection and sight-threatening periocular haemorrhage. METHODS: We compared
      articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in cataract
      surgery. RESULTS: Sub-Tenon's anaesthesia using articaine 2% resulted in a more
      rapid onset of motor block compared with a bupivacaine/lidocaine (P=0.0076).
      Ocular movement scores were significantly lower from 2 min after injection until
      the end of surgery (P=0.031 ANOVA). CONCLUSION: Articaine 2% is safe and
      effective for sub-Tenon's anaesthesia and is a suitable alternative to the
      traditional bupivacaine 0.5%/lidocaine 2% mixture.

PMID- 14722174
TI  - Articaine versus lidocaine plus bupivacaine for peribulbar anaesthesia in
      cataract surgery.
AB  - BACKGROUND: We compared the efficacy and safety of articaine 2% with a mixture of
      lidocaine 2% and bupivacaine 0.5% without hyaluronidase for peribulbar
      anaesthesia in cataract surgery. METHOD: In this double-blind randomized clinical
      study, 58 cataract patients were allocated to receive either articaine 2% with
      epinephrine 1:200 000 or a mixture of equal parts of lidocaine 2% with
      epinephrine 1.25:100 000 and bupivacaine 0.5%. Ocular and eyelid movement scores,
      the number of supplementary injections, total volume of solution used and pain
      and complications during injection and surgery were used as clinical end-points.
      RESULTS: Articaine produced greater akinesia after 5 min (P=0.03). Eighteen
      patients (60%) in the articaine group and 26 (93%) in the lidocaine/bupivacaine
      group required a second injection (P=0.003). A third injection was needed by two
      patients (7%) in the articaine group and 12 (43%) in the lidocaine/bupivacaine
      group (P=0.001). The total mean volume of local anaesthetic required to achieve
      akinesia was mean 9.4 (SD 1.7) ml in the articaine group and 11.28 (1.86) ml in
      the lidocaine/bupivacaine group (P<0.001). Median pain score was lower in the
      articaine group than in lidocaine/bupivacaine group during injection (P=0.004)
      and surgery (P=0.014). There was no difference between the groups for the
      incidence of complications. CONCLUSION: Articaine 2% without hyaluronidase is
      more advantageous than a mixture of lidocaine 2% and bupivacaine 0.5% without
      hyaluronidase for peribulbar anaesthesia in cataract surgery.

PMID- 14722175
TI  - Pain on medical wards in a district general hospital.
AB  - BACKGROUND: Little attention has been paid to pain on medical wards, with
      publications limited to the management of surgical patients. We wanted to
      establish the prevalence and severity of pain in the general medical setting, and
      how this compared with other clinical specialties. METHODS: All consenting adult
      in-patients were assessed daily for 5 days. Patients recorded the occurrence and
      severity of pain, and whether their pain was bearable. The pain team reviewed
      patients with unbearable pain. RESULTS: 1594 questionnaires were completed,
      representing 54% of the target population. 887 patients reported pain, 17% with
      pain scores over 6, and 10% with unbearable pain. The distribution of pain was
      similar for all ward types with 52% of patients on medical wards reporting pain.
      Of these, 20% reported severe pain and 12% unbearable pain. When patients with
      pain scores over 6 were analysed by consultant specialty, elderly care, general
      medicine, and general surgery scored highest. In each specialty 20-25% of
      patients with pain reported a pain score over 6. In patients reviewed by the pain
      team, reasons for poor analgesia included inadequate information, pain
      assessment, analgesic prescribing, and administration and patient reporting.
      CONCLUSION: Patients in all hospital specialities experience pain. Until the
      issue of pain management in medical patients is fully addressed the situation
      will not improve.

PMID- 14722176
TI  - Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask
      insertion.
AB  - BACKGROUND: This study sought to determine the effective concentration for 50% of
      the attempts to secure laryngeal mask insertion (predicted EC(50LMA)) of propofol
      using a target-controlled infusion (Diprifusor) and investigated whether fentanyl
      influenced these required concentrations, respiratory rate (RR) and bispectral
      index (BIS). METHODS: Sixty-four elective unpremedicated patients were randomly
      assigned to four groups (n = 16 for each group) and given saline (control) or
      fentanyl 0.5, 1 or 2 micro g kg(-1). Propofol target concentration was determined
      by a modification of Dixon's up-and-down method. Laryngeal mask airway insertion
      was attempted without neuromuscular blocking drugs after equilibration had been
      established for >10 min. Movement was defined as presence of bucking or gross
      purposeful muscular movement within 1 min after insertion. EC(50LMA) values were
      obtained by calculating the mean of 16 patients in each group. RESULTS: Predicted
      EC(50LMA) of the control, fentanyl 0.5, 1 and 2 micro g kg(-1) groups were 3.25
      (0.20), 2.06 (0.55), 1.69 (0.38) and 1.50 (0.54) micro g ml(-1) respectively;
      those of all fentanyl groups were significantly lower than that of control. RR
      was decreased in relation to the fentanyl dose up to 1 micro g kg(-1). BIS values
      after fentanyl 1 and 2 micro g kg(-1) were significantly greater than in the
      control and 0.5 micro g kg(-1) groups. CONCLUSIONS: A fentanyl dose of 0.5 micro
      g kg(-1) is sufficient to decrease predicted EC(50LMA) with minimum respiratory
      depression and without a high BIS value.

PMID- 14722177
TI  - Predicted values of propofol EC50 and sevoflurane concentration for insertion of
      laryngeal mask Classic and ProSeal.
AB  - BACKGROUND: A new laryngeal mask airway, the ProSeal (PLMA), is said to be more
      difficult to insert than the laryngeal mask airway Classic (CLMA) using propofol
      anaesthesia. Therefore, we expected a greater dose of propofol and sevoflurane to
      be required to insert the PLMA compared with the CLMA. We determined the
      effective concentration 50% (EC(50)) of propofol and end-tidal sevoflurane to
      allow insertion of the PLMA and the CLMA. METHODS: Seventy-six elective female
      patients (aged 20-60 yr and ASA I-II) were randomly assigned to one of four
      groups. Either a PLMA or a CLMA was inserted using either propofol target
      controlled infusion or sevoflurane. Both propofol and sevoflurane targets were
      determined with a modified Dixon's up-and-down method. After equilibration
      between the predetermined blood and effect site concentrations, which had been
      held steady for more than 10 min, LMA insertion was attempted without
      neuromuscular block. RESULTS: The predicted EC(50CLMA) and EC(50PLMA) for
      propofol were 3.14 (0.33) and 4.32 (0.67) micro g ml(-1). E'(CLMA) and E'(PLMA)
      of sevoflurane (mean (SD)) were 2.36 (0.22) and 2.82 (0.45)% (P<0.01 and 0.05,
      respectively). CONCLUSIONS: The estimated concentration of propofol and the
      sevoflurane concentration needed to allow insertion of the ProSeal are
      respectively 38 and 20% greater than those needed for insertion of the Classic
      LMA.

PMID- 14722178
TI  - Effects of halothane on contraction and intracellular calcium in ventricular
      myocytes from streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Some of the cellular targets affected by volatile anaesthetics (e.g.
      halothane) which contribute to the negative inotropic effects of these agents are
      also affected during the progression of diabetic cardiomyopathy. A previous
      report suggested that halothane inhibited contraction to a lesser extent in
      papillary muscle from diabetic animals and so the aim of this study was to
      investigate possible mechanisms underlying this effect. METHODS: Contractility
      and cytosolic calcium ion (Ca(2+)) transients were measured (fura-2) in
      ventricular myocytes isolated from control and streptozotocin (STZ)-induced
      diabetic rats in the absence and presence of halothane 0.6 mmol litre(-1) at 1 Hz
      stimulation. Sarcoplasmic reticulum (SR) Ca(2+) content was assessed by rapid
      application of caffeine. All experiments were carried out at 36-37 degrees C.
      RESULTS: The amplitude of shortening, the electrically evoked Ca(2+) transient,
      SR Ca(2+) content and myofilament Ca(2+) sensitivity, though not altered by STZ
      treatment, were significantly reduced by halothane to a similar extent in control
      and STZ myocytes. The time course of contraction and Ca(2+) transient were
      prolonged in myocytes from STZ-treated rats compared with controls but this was
      not altered further by halothane. STZ treatment appeared to reduce Ca(2+) efflux
      from the cell, an effect reversed by halothane. CONCLUSIONS: In contrast to a
      previous report, we could find no evidence of amelioration of the negative
      inotropic effect of halothane in myocytes from the STZ-induced diabetic rat.
      Contractility, the cytosolic Ca(2+) transient, SR Ca(2+) content and myofilament
      Ca(2+) sensitivity were qualitatively similar in control and STZ myocytes and
      were all depressed to the same extent by halothane.

PMID- 14722179
TI  - Effects of volatile anaesthetic agents on enhanced airway tone in sensitized
      guinea pigs.
AB  - BACKGROUND: Although volatile anaesthetics afford protection against
      bronchospasm, their potential to reverse a sustained constriction of
      hyperreactive airways has not been characterized. Accordingly, we investigated
      the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung
      constriction induced by prolonged stimulation of the muscarinic receptors in
      guinea pigs sensitized to ovalbumin. METHODS: Pulmonary input impedance (ZL) was
      measured using forced oscillations in five groups of ovalbumin-sensitized,
      mechanically ventilated guinea pigs. ZL was measured under baseline conditions,
      during steady-state bronchoconstriction induced by an i.v. infusion of
      methacholine (MCh), and after administration of one of the volatile agents at 1
      MAC after the induction of a steady-state bronchoconstriction. Airway resistance
      (Raw), and parenchymal tissue resistive and elastic coefficients were extracted
      from ZL by model fitting. RESULTS: All four volatile agents exhibited an initial
      relaxation of the MCh-induced airway constriction followed by gradual increases
      in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (SE
      5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had
      shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05,
      respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a
      tendency to enhance airway tone. CONCLUSIONS: Volatile agents can reverse
      sustained MCh-induced airway constriction only transiently in sensitized guinea
      pigs. Isoflurane proved most beneficial in temporally improving lung function in
      the presence of a severe constriction of allergic inflamed airways. Desflurane
      displayed potential to induce further airway constriction.

PMID- 14722180
TI  - Protective ventilation of patients with acute respiratory distress syndrome.
AB  - The majority of patients with acute respiratory distress syndrome (ARDS) require
      mechanical ventilation. This support provides time for the lungs to heal, but the
      adverse effects of mechanical ventilation significantly influence patient
      outcome. Traditionally, these were ascribed to mechanical effects, such as
      haemodynamic compromise from decreased venous return or gross air leaks induced
      by large transpulmonary pressures. More recently, however, the ARDS Network study
      has established the clinical importance of lowering the tidal volume to limit
      overdistension of the lung when ventilating patients with ARDS. This study
      suggests that ventilator-associated lung injury (VALI) caused by overdistension
      of the lung contributes to the mortality of patients with ARDS. Moreover, the
      results from clinical and basic research have revealed more subtle types of VALI,
      including upregulation of the inflammatory response in the injured and
      overdistended lung. This not only damages the lung, but the overflow of
      inflammatory mediators into the systemic circulation may explain why most
      patients who die with ARDS succumb to multi-organ failure rather than respiratory
      failure. The results of these studies, the present understanding of the
      pathophysiology of VALI, and protective ventilatory strategies are reviewed.

PMID- 14722181
TI  - Prediction of the distance from skin to epidural space for low-thoracic epidural
      catheter insertion by computed tomography.
AB  - BACKGROUND: It may be clinically useful to predict the depth of the epidural
      space. METHODS: To investigate the accuracy of preoperative abdominal computed
      tomography (CT) in prediction of the distance for low-thoracic epidural
      insertion, a single group observational study was conducted in 30 male patients
      undergoing elective major abdominal surgery requiring epidural analgesia for
      postoperative pain relief. Using the paramedian approach, low-thoracic epidural
      insertion at T10-11 interspace was performed with a standardized procedure to
      obtain an actual insertion length (AIL). According to the principles of
      trigonometry, an estimated insertion length (EIL) was calculated as 1.26 times
      the distance from skin to epidural space measured from the preoperative abdominal
      CT. RESULTS: The mean (SD) EIL and AIL were 5.5 (0.7) and 5.1 (0.6) cm,
      respectively, with a significant correlation (r=0.899, P<0.01). The EIL tended to
      have a higher value than the AIL (0.4 (0.3) cm). There were significant
      correlations of both EIL and AIL with weight (P<0.01), BMI (P<0.01), and body fat
      percentage (P<0.01), but not with height (P>0.05). CONCLUSIONS: We conclude that
      the preoperative abdominal CT is helpful in prediction of the distance for low
      thoracic epidural insertion using the paramedian approach.

PMID- 14722182
TI  - Leg weakness is a complication of ilio-inguinal nerve block in children.
AB  - BACKGROUND: Ilio-inguinal nerve block is commonly used in children to provide
      analgesia after surgery in the groin. Several case reports and clinical studies
      have described leg weakness after this technique and suggest that it may caused
      by inadvertent femoral nerve block. No prospective studies describing the
      incidence of this complication have been published. METHODS: We carried out a
      prospective, observational study to find out how many children had leg weakness
      after ilio-inguinal nerve block. We studied 200 children having day-case surgery
      in the groin under a general anaesthetic with an ilio-inguinal nerve block. All
      children performed a simple leg-raising test with each leg before induction of
      general anaesthesia with a standardized ilio-inguinal nerve block on the side of
      surgery. When the child was awake and comfortable after surgery, they repeated
      the leg-raising test. RESULTS: Sixteen of 182 children (8.8%) had leg weakness
      after surgery on the side of the nerve block only, as detected by a leg-raising
      test. CONCLUSIONS: Leg weakness consistent with a femoral nerve block occurs
      after ilio-inguinal nerve block in approximately one in nine children.

PMID- 14722183
TI  - Animal dependence of inhaled anaesthetic requirements in cats.
AB  - BACKGROUND: The minimum alveolar concentration (MAC) of an inhaled anaesthetic
      describes its potency as a general anaesthetic. Individuals vary in their
      sensitivity to anaesthetics and we sought to determine whether an individual
      animal's sensitivity to inhaled anaesthetics would be maintained across different
      agents. METHODS: Six female mongrel cats, age 2 yr (range 1.8-2.3) and mean
      weight 3.5 (SD 0.3) kg, were studied on three separate occasions over a 12-month
      period to determine the MAC of isoflurane, sevoflurane and desflurane. Induction
      of anaesthesia in a chamber was followed by orotracheal intubation and
      maintenance of anaesthesia with the inhaled agent in oxygen delivered via a non
      rebreathing circuit. MAC was determined in triplicate using standard tail-clamp
      technique. RESULTS: Mean MAC values for isoflurane, sevoflurane and desflurane
      were 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%, respectively. Body
      temperature, systolic pressure and Sp(O(2)) recorded at the time of MAC
      determinations for isoflurane, sevoflurane and desflurane were 38.3 (0.3), 38.6
      (0.1) and 38.3 (0.3) degrees C; 71.2 (8.3), 74.6 (15.9) and 88.0 (12.0) mmHg;
      99.2 (1.1), 99.1 (1.3) and 99.4 (0.8)%, respectively. Both the anaesthetic agent
      and the individual cat had significant effects on MAC. Correlation coefficients
      for comparisons between desflurane and isoflurane, desflurane and sevoflurane,
      and sevoflurane and isoflurane were 0.90, 0.89 and 0.97, respectively.
      CONCLUSIONS: These findings show that an individual has a consistent degree of
      sensitivity to a variety of inhaled anaesthetics, suggesting a genetic basis for
      sensitivity to inhaled anaesthetic effects.

PMID- 14722184
TI  - Protective effects of early treatment with propofol on endotoxin-induced acute
      lung injury in rats.
AB  - BACKGROUND: To investigate the effects of propofol administration on acute lung
      injury in endotoxin-induced shock in rats. METHODS: Seventy-six male Wistar rats
      were randomly assigned to one of five groups: (i) saline control; (ii) endotoxin
      alone (receiving lipopolysaccharide (LPS) 8 mg kg(-1) i.v.); (iii) pretreatment
      with propofol 1 h before LPS; (iv) simultaneous treatment with propofol and LPS;
      (v) post-treatment with propofol 1 h after LPS. During the 5 h after LPS
      injection, survival rates were recorded. Lung tissue was sampled to measure
      values of nitrite/nitrates (NO(2-)/NO(3-)) and tumour necrosis factor (TNF)-alpha
      in bronchoalveolar lavage (BAL) fluid, and wet-to-dry lung weight ratio,
      pulmonary permeability index, BAL protein and expression of inducible nitric
      oxide synthase (iNOS) and nitrotyrosine (NT). RESULTS: Compared with the
      endotoxaemic group, both the pre- and simultaneous treatment groups showed
      significantly improved 5 h survival rates, and attenuated endotoxin-induced
      increased BAL fluid NO(2-) /NO(3-) and TNF-alpha, iNOS mRNA and NT expression in
      lung tissue, and decreased pulmonary microvascular permeability. These beneficial
      effects were blunted in the post-treatment group. CONCLUSIONS: These findings
      indicate that early administration of propofol may provide protective effects
      against endotoxin-induced acute lung injury.

PMID- 14722186
TI  - Angina bullosa haemorrhagica presenting as acute upper airway obstruction.
AB  - We report a case of acute upper airway obstruction caused by a rapidly expanding
      blood-filled bulla in the oropharynx (angina bullosa haemorrhagica), requiring
      tracheal intubation. The larynx could not be visualized by either awake
      fibreoptic laryngoscopy or direct laryngoscopy under anaesthesia. Surgical
      tracheostomy was therefore performed under general anaesthesia.

PMID- 14722185
TI  - Tracheostomy in a patient with severe acute respiratory syndrome.
AB  - The coronavirus which causes severe acute respiratory syndrome (SARS) is a
      virulent and highly contagious organism. Of the 1755 SARS patients in Hong Kong,
      over 400 were healthcare workers. Meticulous attention to infection control and
      teamwork are essential to minimize cross-contamination and prevent staff from
      contracting the illness. These points are especially pertinent when
      anaesthetizing SARS patients for high-risk procedures such as tracheostomy. We
      describe the management of such a case.

PMID- 14722187
TI  - Locked-in syndrome: a catastrophic complication after surgery.
AB  - We describe the locked-in syndrome in a 31-yr-old patient after right upper
      lobectomy for suspected metastasis. After surgery, vertical eye movement was her
      only means of communication. She remained in a 'locked-in' state for 7 months
      before dying. Post-mortem examination showed extensive metastatic tumour
      deposition in the ventral pons. We discuss the clinical features of this syndrome
      and factors that may affect onset, diagnosis and management.

PMID- 14722188
TI  - Acute motor axonal polyneuropathy after a cisatracurium infusion and concomitant
      corticosteroid therapy.
AB  - A 40-yr-old male was admitted to the intensive care unit following blunt chest
      trauma. He had multiple rib fractures, bilateral pneumothoraces, and acute
      respiratory failure requiring mechanical ventilation. Sedation was achieved with
      midazolam and morphine, and later with propofol. The patient was paralysed with a
      continuous infusion of cisatracurium 1.42-5.75 micro g kg(-1) min(-1).
      Methylprednisolone 125 mg i.v. every 12 h was also started. After discontinuation
      of the cisatracurium infusion 7 days later, the patient manifested a flaccid
      quadriplegia with absence of deep-tendon reflexes. No sensory deficits were
      observed. Electromyography (EMG), repetitive nerve stimulation testing, and
      single fibre EMG (SFEMG) were performed at regular intervals after stopping
      cisatracurium. Clinical symptoms and electrophysiological examinations supported
      the diagnosis of acute motor axonal polyneuropathy related to concomitant
      administration of cisatracurium and corticosteroid therapy.

PMID- 14722189
TI  - Epidural abscess complicating insertion of epidural catheters.

PMID- 14722190
TI  - Combined spinal epidural anaesthesia is better than spinal or epidural alone.

PMID- 14722191
TI  - New method to evaluate the practice of positive pressure ventilation in intensive
      care units.

PMID- 14722192
TI  - Sub-Tenon's infiltration using bupivacaine 0.5% decreases acute postoperative
      pain.

PMID- 14722193
TI  - Successful use of the airway management device.

PMID- 14722195
TI  - Abstracts of the Anaesthetic Research Society Meeting. University of Manchester,
      November 20-21, 2003.

PMID- 14722194
TI  - Acute fatal haemorrhage during percutaneous dilatational tracheostomy.

PMID- 14722196
TI  - Acquired resistance of human T cells to sulfasalazine.

PMID- 14722197
TI  - Non-surgical treatment of osteoarthritis: a half century of "advances".

PMID- 14722198
TI  - Hepatic manifestations of autoimmune rheumatic diseases.
AB  - Hepatic manifestations in autoimmune disease include chronic active hepatitis,
      primary biliary cirrhosis, primary sclerosing cholangitis, and nodular
      regenerative hyperplasia. These diseases are rare and may occur concomitantly or
      serially. Clinicians must be aware of the possibility of liver disease so that it
      can be treated as soon as possible.

PMID- 14722199
TI  - Case Number 29: Ochronosis: synovial histopathological characteristics.

PMID- 14722200
TI  - Acquired resistance of human T cells to sulfasalazine: stability of the resistant
      phenotype and sensitivity to non-related DMARDs.
AB  - BACKGROUND: A recent study from our laboratory showed that induction of the
      multidrug resistance related drug efflux pump ABCG2 contributed to acquired
      resistance of human T cells to the disease modifying antirheumatic drug (DMARD)
      sulfasalazine (SSZ). OBJECTIVES: To investigate the duration of SSZ resistance
      and ABCG2 expression after withdrawal of SSZ and rechallenging with SSZ, and to
      assess the impact of SSZ resistance on responsiveness to other DMARDs. METHODS:
      Human CEM cells (T cell origin) with acquired resistance to SSZ (CEM/SSZ) were
      characterised for (a) SSZ sensitivity and ABCG2 expression during withdrawal and
      rechallenge of SSZ, and (b) antiproliferative efficacy of other DMARDs. RESULTS:
      ABCG2 protein expression was stable for at least 4 weeks when CEM/SSZ cells were
      grown in the absence of SSZ, but gradually declined, along with SSZ resistance
      levels, to non-detectable levels after withdrawal of SSZ for 6 months.
      Rechallenging with SSZ led to a rapid (<2.5 weeks) resumption of SSZ resistance
      and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed
      diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8
      fold), were moderately more sensitive (1.6-2.0 fold) to cyclosporin A and
      chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid
      dexamethasone as compared with parental CEM cells. CONCLUSION: The drug efflux
      pump ABCG2 has a major role in conferring resistance to SSZ. The collateral
      sensitivity of SSZ resistant cells for some other (non-related) DMARDs may
      provide a further rationale for sequential mono- or combination therapies with
      distinct DMARDs upon decreased efficacy of SSZ.

PMID- 14722201
TI  - Development of sulfasalazine resistance in human T cells induces expression of
      the multidrug resistance transporter ABCG2 (BCRP) and augmented production of
      TNFalpha.
AB  - OBJECTIVE: To determine whether overexpression of cell membrane associated drug
      efflux pumps belonging to the family of ATP binding cassette (ABC) proteins
      contributes to a diminished efficacy of sulfasalazine (SSZ) after prolonged
      cellular exposure to this disease modifying antirheumatic drug (DMARD). METHODS:
      A model system of human T cells (CEM) was used to expose cells in vitro to
      increasing concentrations of SSZ for a period of six months. Cells were then
      characterised for the expression of drug efflux pumps: P-glycoprotein (Pgp,
      ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer
      resistance protein (BCRP, ABCG2). RESULTS: Prolonged exposure of CEM cells to SSZ
      provoked resistance to SSZ as manifested by a 6.4-fold diminished
      antiproliferative effect of SSZ compared with parental CEM cells. CEM cells
      resistant to SSZ (CEM/SSZ) showed a marked induction of ABCG2/BCRP, Pgp
      expression was not detectable, while MRP1 expression was even down regulated. A
      functional role of ABCG2 in SSZ resistance was demonstrated by 60% reversal of
      SSZ resistance by the ABCG2 blocker Ko143. Release of the proinflammatory
      cytokine tumour necrosis factor alpha (TNFalpha) was threefold higher in CEM/SSZ
      cells than in CEM cells. Moreover, twofold higher concentrations of SSZ were
      required to inhibit TNFalpha release from CEM/SSZ cells compared with CEM cells.
      CONCLUSION: Collectively, ABCG2 induction, augmented TNFalpha release, and less
      efficient inhibition of TNFalpha production by SSZ may contribute to diminished
      efficacy after prolonged exposure to SSZ. These results warrant further clinical
      studies to verify whether drug efflux pumps, originally identified for their
      roles in cytostatic drug resistance, can also be induced by SSZ or other DMARDs.

PMID- 14722202
TI  - Infliximab treatment for rheumatoid arthritis, with dose titration based on the
      Disease Activity Score: dose adjustments are common but not always sufficient to
      assure sustained benefit.
AB  - BACKGROUND: Randomised controlled trials have shown that treatment with anti
      tumour necrosis factor (anti-TNF) agents is effective in refractory rheumatoid
      arthritis (RA). OBJECTIVE: To determine the effectiveness of anti-TNF in a
      general unselected group of patients with refractory RA. METHODS: 68 patients
      with active RA despite treatment with disease modifying antirheumatic drugs were
      studied during 12 infliximab infusions. Infliximab (3 mg/kg/infusion) was given
      every 8 or 6 weeks. Clinical efficacy was assessed by the Disease Activity Score
      (DAS) index (44 joints). Dose adjustments were based on residual disease activity
      (DAS score >2.4). The primary end points were the percentage of patients
      achieving good or moderate response by the EULAR response criteria and the
      proportion of patients requiring dose adjustment. RESULTS: 20 (29%) patients
      discontinued treatment owing to side effects, early inefficacy, or other
      considerations. Among the patients who continued treatment, 27 (56%) and 32 (67%)
      were responders on the 6th and 12th infliximab infusion, respectively. In the
      same patients, disease activity gradually improved without modifications in the
      initial dosing in 10 (21%), whereas in 38 (79%) the dose of infliximab and/or
      methotrexate was increased. Intensification of treatment led to a significant
      decrease in the mean DAS score in this group (from 5.27 just before dose
      modification to 4.54 before the 12th infusion, p<0.002). The EULAR response
      category improved in only 10/38 (26%), however. CONCLUSIONS: In this initial
      observational study of patients with RA treated with recommended doses of
      infliximab, adjustments in treatment were common but not always sufficient to
      maintain adequate disease control. Longitudinal controlled trials are needed to
      define the optimal dose escalation in patients with suboptimal response.

PMID- 14722203
TI  - Infliximab in active early rheumatoid arthritis.
AB  - OBJECTIVE: To examine the impact of the combination of infliximab plus
      methotrexate (MTX) on the progression of structural damage in patients with early
      rheumatoid arthritis (RA). METHODS: Subanalyses were carried out on data for
      patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy
      (ATTRACT) study, in which 428 patients with active RA despite MTX therapy
      received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q)
      4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined
      as disease duration of 3 years or less; 82 of the 428 patients (19%) met this
      definition. Structural damage was assessed with the modified van der Heijde-Sharp
      score. The changes from baseline to week 102 in total modified van der Heijde
      Sharp score were compared between the infliximab plus MTX groups and the MTX-only
      group. RESULTS: The erosion and joint space narrowing scores from baseline to
      week 102 in the cohort of patients with early RA decreased significantly in each
      infliximab dose regimen compared with the MTX-only regimen. Consistent benefit
      was seen in the joints of both hands and feet. CONCLUSIONS: Infliximab combined
      with MTX inhibited the progression of structural damage in patients with early RA
      during the 2 year period of treatment. Early intervention with infliximab in
      patients with active RA despite MTX therapy may provide long term benefits by
      preventing radiographic progression and preserving joint integrity.

PMID- 14722204
TI  - Treatment of refractory psoriatic arthritis with infliximab: a 12 month
      observational study of 16 patients.
AB  - OBJECTIVE: To evaluate the effectiveness and toxicity of infliximab in patients
      with recalcitrant psoriatic arthritis (PsA). METHODS: Patients with treatment
      resistant PsA and at least six actively inflamed joints, who had failed to
      respond to at least two disease modifying agents, were included. Infliximab (5
      mg/kg) was given at weeks 0, 2, 6, and every 6-8 weeks pending response. Clinical
      and laboratory measures included actively inflamed joint count (AJC), swollen
      joint count (SJC), psoriasis severity (PASI), HAQ, and SF-36. Response was
      defined as at least a 30% reduction in AJC and PASI. Differences from baseline
      were analysed using the signed rank test. RESULTS: Sixteen patients (12 male, 4
      female), mean age 48 and disease duration 14 years, were included. At baseline
      the mean AJC was 22.5 and mean PASI 4.5. Eleven patients continued receiving
      methotrexate. The AJC did not show a statistically significant response. SJC
      improved significantly at week 54 (p = 0.01). The PASI improved significantly at
      weeks 14 (p = 0.001) and 30 (p = 0.002) and CRP was reduced significantly at week
      30 (p = 0.02). The HAQ score improved at week 30 (p = 0.02). Six patients became
      positive for dsDNA without clinical features of a connective tissue disease. Six
      patients discontinued treatment owing to lack of efficacy (1) and toxicity (5).
      Other serious adverse events included: urticaria (3); thrombocytopenia (1); lower
      gastrointestinal bleeding (2); severe diarrhoea (2); serious infections (6).
      Raised transaminases, at least 1.5x normal, occurred in four patients.
      CONCLUSION: In refractory PsA, infliximab led to a marked improvement in
      psoriasis but modest response in joint disease. Toxicity and rate of treatment
      termination was high.

PMID- 14722205
TI  - Development of the PsAQoL: a quality of life instrument specific to psoriatic
      arthritis.
AB  - BACKGROUND: Patient reported outcome measures used in studies of psoriatic
      arthritis (PsA) have been found to be inadequate for determining the impact of
      the disease from the patient's perspective. OBJECTIVE: To produce the PsAQoL, a
      PsA-specific quality of life (QoL) instrument, employing the needs based model of
      QoL that would be relevant and acceptable to respondents, valid, and reliable.
      METHODS: Content was derived from qualitative interviews conducted with patients
      with PsA. Face and content validity were assessed by field test interviews with a
      new sample of patients with PsA. A postal survey was conducted to improve the
      scaling properties of the new measure. Finally, a test-retest postal survey was
      used to identify the final measure and to test its scaling properties,
      reliability, internal consistency, and validity. RESULTS: Analysis of the
      qualitative interview transcripts identified a 51 item questionnaire. Field test
      interviews confirmed the acceptability and relevance of the measure. Analysis of
      data from the first postal survey (n = 94) reduced the questionnaire to 35 items.
      Rasch analysis of data from the test-retest survey (n = 286) identified a 20 item
      version of the PsAQoL with good item fit. This version had excellent internal
      consistency (alpha = 0.91), test-retest reliability (0.89), and validity.
      CONCLUSIONS: The PsAQoL is a valuable tool for assessing the impact of
      interventions for PsA in clinical studies and trials. It is well accepted by
      patients, taking about three minutes to complete, is easy to administer, and has
      excellent scaling and psychometric properties.

PMID- 14722206
TI  - Inhibition of leukotriene B4-induced CD11B/CD18 (Mac-1) expression by BIIL 284, a
      new long acting LTB4 receptor antagonist, in patients with rheumatoid arthritis.
AB  - BACKGROUND: Leukotriene B4 (LTB(4)) has a key role in the pathophysiology of
      rheumatoid arthritis (RA). OBJECTIVE: To investigate the inhibition of ex vivo
      LTB(4)-induced Mac-1 (CD11b/CD18) expression in leucocytes of patients with RA by
      the new oral LTB(4) receptor antagonist BIIL 284. METHODS: The pharmacokinetics
      and inhibition of LTB(4)-induced Mac-1 expression of BIIL 284 were characterised
      in 26 adult patients with RA who were treated with BIIL 284 25 mg, 150 mg, or
      placebo given once a day for 14 days according to a double blind, randomised,
      parallel group design. RESULTS: T(max) of BIIL 315 in plasma (main metabolite and
      active principle of BIIL 284 in plasma) was achieved about four hours after drug
      administration, and C(max,ss) and AUC(0-6h,ss) increased in proportion to the
      dosage. 100% inhibition of LTB(4)-induced MAC-1 expression was reached after two
      hours (150 mg) or four hours (25 mg), showing a statistically significant
      difference in comparison with placebo (p<0.005). A longlasting dynamic effect was
      seen consistently even when plasma concentrations declined to very low values 24
      hours after administration. Secondary clinical efficacy end points remained
      unchanged probably owing to the short duration of treatment. Adverse events (AEs)
      were reported in 12 patients during the study. No serious AEs or laboratory AEs
      were seen. CONCLUSIONS: Both the 25 mg and 150 mg doses of BIIL 284 safely and
      effectively inhibit Mac-1 expression on neutrophils; thus longer treatment with
      BIIL 284 may result in clinical benefit for patients with RA.

PMID- 14722207
TI  - Self reported non-vertebral fractures in rheumatoid arthritis and population
      based controls: incidence and relationship with bone mineral density and clinical
      variables.
AB  - OBJECTIVE: To compare the incidence of self reported non-vertebral fractures
      after RA diagnosis between female patients with RA and control subjects, and to
      explore possible associations between non-vertebral fractures and bone mineral
      density (BMD), disease, and demographic factors. METHODS: 249 women (mean age
      63.0 years) recruited from a county register of patients with RA and population
      controls (n = 249) randomly selected after matching for age, sex, and residential
      area were studied. Data on previous non-vertebral fractures were obtained from a
      detailed questionnaire, and BMD was measured at the hip and spine. RESULTS: 53
      (21.3%) patients with RA had had 67 fractures after RA diagnosis, the
      corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for
      paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The
      overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively,
      but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2
      to 394.5). Patients with a positive fracture history had longer disease duration,
      were more likely to have at least one deformed joint, and had lower age and
      weight adjusted BMD than those with no fracture history. In logistic regression
      analysis, fracture history was independently related to BMD only. CONCLUSIONS:
      With the probable exception of hip fractures, non-vertebral fractures do not seem
      to be a substantial burden in RA. Similar independent relationships between
      levels of BMD and fracture history were found in patients with RA and in
      population based controls.

PMID- 14722208
TI  - Access to bone densitometry increases general practitioners' prescribing for
      osteoporosis in steroid treated patients.
AB  - BACKGROUND: Availability of access to bone densitometry in the UK varies widely
      and there are concerns as to appropriate prescribing. Studies suggest inadequate
      use of osteoporosis prophylaxis in steroid users, despite recent guidelines.
      OBJECTIVE: To examine in a case-control study whether access to bone densitometry
      affects GPs' osteoporosis prescribing in high risk steroid users. METHOD: 10
      general practices were included, five from primary care trusts (PCTs) with access
      to bone densitometry and five with limited access. Patients receiving
      prednisolone for >3 months were identified by database search. Patients receiving
      no prophylaxis other than calcium and vitamin D (Ca/D) were subsequently
      included. Appropriate patients in five practices were offered DXA scan (cases)
      and review. Patients in practices without access to scans (controls) were
      reviewed. GPs' opinions leading to treatment were sought by structured
      questionnaire. RESULTS: 132 (0.12%) patients were receiving prednisolone for >/=3
      months, but no osteoporosis prophylaxis other than Ca/D. Pre-study prophylaxis
      ranged from 18 to 36%. Of 48 patients scanned, 21 (44%) were abnormal and 18
      (38%) received new treatment. 13/44 (30%) controls received new treatment. 10/21
      (48%) with abnormal scans started a bisphosphonate, compared with 7/44 (16%)
      controls (RR = 3, p = 0.004). No difference in risk factors for fracture was
      found in treated and untreated controls. CONCLUSIONS: GPs were three times more
      likely to start potent osteoporosis treatment after abnormal scans than GPs
      relying on clinical information. In practice, risk factors were not adequately
      assessed. Database searches may identify patients needing osteoporosis
      prophylaxis; however, DXA enables more appropriate patient treatment.

PMID- 14722209
TI  - Decreased prevalence of atopy in paediatric patients with familial Mediterranean
      fever.
AB  - BACKGROUND: A number of inflammatory diseases, including familial Mediterranean
      fever (FMF), have been shown to be driven by a strongly dominated Th1 response,
      whereas the pathogenesis of atopic diseases is associated with a Th2 response.
      OBJECTIVE: Because dominance of interferon gamma has the potential of inhibiting
      Th2 type responses-that is, development of allergic disorders, to investigate
      whether FMF, or mutations of the MEFV gene, have an effect on allergic diseases
      and atopy that are associated with an increased Th2 activity. METHOD: Sixty
      children with FMF were questioned about allergic diseases such as asthma,
      allergic rhinitis, and atopic dermatitis, as were first degree relatives, using
      the ISAAC Study phase II questionnaire. The ISAAC Study phase II was performed in
      a similar ethnic group recruited from central Anatolia among 3041 children. The
      same skin prick test panel used for the ISAAC Study was used to investigate the
      presence of atopy in patients with FMF and included common allergens. RESULTS:
      The prevalences of doctor diagnosed asthma, allergic rhinitis, and eczema were
      3.3, 1.7, and 3.3%, respectively, in children with FMF, whereas the corresponding
      prevalences in the ISAAC study were 6.9, 8.2, and 2.2%, respectively. Only the
      prevalence of allergic rhinitis was significantly different between the two
      groups (p<0.001). The prevalence of atopy in these patients with FMF (4/60 (7%))
      was significantly lower than in the children of the population based study
      (20.6%) (p<0.001). CONCLUSION: Family Mediterranean fever seems to be protective
      against development of atopic sensitisation and allergic rhinitis.

PMID- 14722210
TI  - Dual effects of 17beta-oestradiol on interleukin 1beta-induced proteoglycan
      degradation in chondrocytes.
AB  - OBJECTIVE: To determine whether 17beta-oestradiol (E2) modulates interleukin (IL)
      1beta-induced proteoglycan degradation in chondrocytes, and to analyse the part
      played by metalloproteinases (MMPs) in this process. METHODS: Primary cultured
      rabbit articular chondrocytes were prepared and treated with 10 ng/ml IL1beta
      combined or not with 0.1-10 nM E2. Neosynthesised proteoglycans (PGs) were
      evaluated after incorporation of [(35)SO(4)]sulphate and further analysed after
      chromatography on a Sepharose 2B column. Chondrocyte mRNA levels of aggrecan, MMP
      1, -3, -13, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were studied by
      northern blot. MMP-1 activity was measured by zymography. MMP-1 gene
      transcription was studied by transient transfection of chondrocytes with an MMP-1
      luciferase construct. RESULTS: E2 modulated the IL1beta-induced total sulphated
      PGs in rabbit articular chondrocytes, which decreased as the E2 concentration was
      increased. At a low concentration (0.1 nmol/l) E2 counteracts the IL1beta-induced
      decrease in sulphated PG, while at high concentration (10 nmol/l) E2 enhances the
      IL1beta effects. A biphasic E2 effect was also observed on IL1beta-induced
      disaggregation of PG, 53-58 kDa gelatinolytic activity, and MMP-1, -3, and -13
      mRNA levels. In contrast, E2 did not modify the level of aggrecan mRNA and had no
      effect on TIMP-1 mRNA expression. Finally, simultaneous addition of IL1beta and
      E2 (0.1-10 nmol/l) did not modify IL1beta-induced MMP-1-luciferase activity,
      suggesting that E2 effects probably occur at the post-transcriptional level of
      MMP gene expression. CONCLUSION: Oestrogen concentration may have an inverse
      effect on IL1beta stimulated proteoglycan degradation and MMP production by
      chondrocytes.

PMID- 14722211
TI  - Severity and extent of osteoarthritis and low grade systemic inflammation as
      assessed by high sensitivity C reactive protein.
AB  - BACKGROUND: Although osteoarthritis (OA) is thought to derive from defective
      chondrocyte metabolism and thus inherently lack the large scale systemic response
      of rheumatoid arthritis, there is increasing interest in the acute phase proteins
      in OA. OBJECTIVE: To assess the association between high sensitivity C reactive
      protein (hsCRP) and severity and extent of OA in patients with advanced hip and
      knee OA. METHODS: Preoperative hsCRP was measured in frozen serum samples from
      770 consecutive patients with hip or knee joint replacement due to advanced OA
      recruited between 1995 and 1996. Pain was measured by a visual analogue scale and
      the Western Ontario and McMaster Universities OA index (WOMAC). The extent of OA
      in different joints was assessed clinically and radiographically. RESULTS: The
      (geometric) mean hsCRP was 2.5 mg/l among all patients. Severity of pain was
      associated with mean hsCRP (adjusted elevation highest v lowest quintile = 35%, p
      = 0.01) after controlling for known or suspected predictors of hsCRP, including
      age, smoking, and body mass index. Neither the bilateral nor the generalised
      extent of OA, nor any of the dimensions of the WOMAC were associated with mean
      hsCRP levels. CONCLUSIONS: Severity of pain, but not extent of OA, was associated
      with hsCRP levels in this group of patients with advanced OA. Longitudinal
      studies with repeated assessments of hsCRP and pain are needed to assess the
      possible value of hsCRP for monitoring or predicting the clinical course of OA.

PMID- 14722212
TI  - Methotrexate treatment in juvenile idiopathic arthritis: when is the right time
      to stop?
AB  - OBJECTIVES: To investigate whether prolonged methotrexate (MTX) treatment after
      induction of remission influences the subsequent duration of remission in
      patients with juvenile idiopathic arthritis (JIA), and to analyse the usefulness
      of myeloid related proteins 8 and 14 (MRP8/MRP14) as predictive markers for the
      stability of remission at the time when MTX is withdrawn. METHODS: Twenty five
      patients with oligoarticular and polyarticular JIA who received MTX to induce
      remission were followed up. MTX treatment was stopped after a mean of 3.8 months
      (group 1) or 12.6 months (group 2) after remission was documented. Differences in
      the number of relapses between these groups were looked for. Additionally,
      MRP8/MRP14 were analysed by ELISA in 22 patients. RESULTS: No difference was
      found in the number of relapses between patients with prolonged or early
      discontinued MTX treatment. Patients who were in stable remission had
      significantly lower MRP levels when MTX was discontinued than patients with
      relapses. With a cut off point for MRP8/MRP14 at 250 ng/ml, sensitivity and
      specificity were 100% and 70%, respectively. CONCLUSION: Longer duration of MTX
      treatment after induction of remission does not generally improve the status of
      remission in patients with JIA. Residual synovial inflammation seems to influence
      the rate of relapses after discontinuation of MTX treatment. MRP8/MRP14 indicate
      residual activity even in the absence of other laboratory or clinical signs of
      continuing inflammation. Normal serum concentrations of MRP8/MRP14 in clinical
      inactive arthritis may help to identify patients in whom MTX can be safely
      withdrawn after remission is achieved.

PMID- 14722213
TI  - Secondary addition of methotrexate to partial responders to etanercept alone is
      effective in severe rheumatoid arthritis.

PMID- 14722214
TI  - Blunted coronary flow reserve in systemic sclerosis: a sign of cardiac
      involvement in asymptomatic patients.

PMID- 14722215
TI  - Incidentally discovered asymptomatic necrotising intra-abdominal vasculitis after
      peripheral gastric bypass surgery for morbid obesity.

PMID- 14722216
TI  - Ultrasound detection of knee patellar enthesitis: a comparison with magnetic
      resonance imaging.

PMID- 14722217
TI  - Longlasting effects of immunoadsorption in severe Sjogren's syndrome.

PMID- 14722218
TI  - Juvenile temporal arteritis and activated protein C resistance.

PMID- 14722219
TI  - Serum osteoprotegerin but not receptor activator of NF-kappaB ligand correlates
      with Larsen score in rheumatoid arthritis.

PMID- 14722220
TI  - Successful management of neonatal cryoglobulinaemia after a gemellar pregnancy in
      a woman with symptomatic type I cryoglobulinaemia.

PMID- 14722221
TI  - Primary Raynaud's phenomenon in monozygotic twins.

PMID- 14722222
TI  - Interferon-gamma inhibits transforming growth factor-beta production in human
      airway epithelial cells by targeting Smads.
AB  - Because interferon (IFN)-gamma may attenuate pulmonary fibrosis, we hypothesized
      that IFN-gamma may regulate transforming growth factor (TGF)-beta production by
      airway epithelial cells. Human bronchial epithelial cells (HBECs) were incubated
      with IFN-gamma +/- TGF-beta1, -beta3, or interleukin (IL)-1beta, platelet-derived
      growth factor (PDGF), epidermal growth factor, and IL-4. TGF-beta2 protein was
      measured by enzyme-linked immunosorbent assay and mRNA expression for TGF-beta2,
      Smad 2, 3, 4, and 7 was evaluated by real-time reverse transcriptase-polymerase
      chain reaction. Localization of Smads 2, 3, 4, and 7 was evaluated by
      immunostaining. Exogenous TGF-beta1 and 3, IL-1beta, PDGF, and IL-4 enhanced TGF
      beta2 release by HBECs (P < 0.01). IFN-gamma reduced basal and TGF-beta or IL-4
      augmented TGF-beta2 release, but had little effect on IL-1beta- or PDGF-augmented
      TGF-beta2 release. IFN-gamma stimulated Smad 7 protein and mRNA expression. Smad
      7-specific siRNA decreased Smad 7 protein expression both in control and IFN
      gamma-treated cells. The inhibitory effect of IFN-gamma on TGF-beta2 production
      was abrogated when the HBECs were treated with Smad 7 siRNA. These results
      suggest that IFN-gamma down regulates TGF-beta2 production by HBECs by regulating
      Smad 7. Through this mechanism, IFN-gamma may play an important role in tissue
      remodeling.

PMID- 14722223
TI  - Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in
      allergic mice.
AB  - Little is known about effects of smoking on airway inflammation in asthma. We
      tested the hypothesis that smoking enhances established airway inflammation in a
      mouse model of allergic asthma. C57Bl/6j mice were sensitized to ovalbumin (OVA)
      and challenged with OVA (OVA-mice) or sham-sensitized to phosphate-buffered
      saline (PBS) and challenged with PBS aerosols (PBS-mice) for 7 wk. At 4 wk, mice
      were additionally exposed to air (nonsmoking controls) or mainstream smoke for 3
      wk. Using whole body plethysmography, we found OVA-induced bronchoconstriction to
      be significantly inhibited in smoking OVA-mice as compared with nonsmoking OVA
      mice (1 +/- 2% increase versus 22 +/- 6% increase in enhanced pause,
      respectively). Smoking did not change airway hyperresponsiveness (AHR) to
      methacholine in PBS-mice, yet significantly attenuated AHR in OVA-mice 24 h after
      OVA challenge as compared with nonsmoking mice. This was accompanied by reduced
      eosinophil numbers in lung lavage fluid and tissue of smoking OVA-mice compared
      with nonsmoking OVA-mice. In contrast to our hypothesis, short-term smoking
      reduced responsiveness to OVA and methacholine in OVA-mice and decreased airway
      inflammation when compared with nonsmoking mice. This effect of smoking may be
      different for long-term smoking, in which remodeling effects of smoking can be
      expected to interrelate with remodeling changes caused by asthmatic disease.

PMID- 14722224
TI  - Specific inhibition of type I interferon signal transduction by respiratory
      syncytial virus.
AB  - Respiratory viruses often express mechanisms to resist host antiviral systems,
      but the biochemical basis for evasion of interferon effects by respiratory
      syncytial virus (RSV) is poorly defined. In this study, we identified RSV effects
      on interferon (IFN)-dependent signal transduction and gene expression in human
      airway epithelial cells. Initial experiments demonstrated inhibition of antiviral
      gene expression induced by IFN-alpha and IFN-beta, but not IFN-gamma, in
      epithelial cells infected with RSV. Selective viral effects on type I IFN
      dependent signaling were confirmed when we observed impaired type I, but not type
      II, IFN-induced activation of the transcription factor Stat1 in RSV-infected
      cells. RSV infection of airway epithelial cells resulted in decreased Stat2
      expression and function with preservation of upstream signaling events, providing
      a molecular mechanism for viral inhibition of the type I IFN JAK-STAT pathway.
      Furthermore, nonspecific pharmacologic inhibition of proteasome function in RSV
      infected cells restored Stat2 levels and IFN-dependent activation of Stat1. The
      results indicate that RSV acts on epithelial cells in the airway to directly
      modulate the type I IFN JAK-STAT pathway, and this effect is likely mediated
      though proteasome-dependent degradation of Stat2. Decreased antiviral gene
      expression in RSV-infected airway epithelial cells may allow RSV replication and
      establishment of a productive viral infection through subversion of IFN-dependent
      immunity.

PMID- 14722225
TI  - Secondary structure models of the nuclear internal transcribed spacer regions and
      5.8S rRNA in Calciodinelloideae (Peridiniaceae) and other dinoflagellates.
AB  - Secondary structure models of the 5.8S rRNA and both internal transcribed spacers
      (ITS1 and ITS2) are proposed for Calciodinelloideae (Peridiniaceae) and are also
      plausible for other dinoflagellates. The secondary structure of the 5.8S rRNA
      corresponds to previously developed models, with two internal paired regions and
      at least one 5.8S rRNA-28S rRNA interaction. A general secondary structure model
      of ITS1 for Calciodinelloideae (and other dinoflagellates), consisting of an open
      multibranch loop with three major helices, is proposed. The homology of these
      paired regions with those found in other taxa, published in previous studies
      (e.g. yeast, green algae and Platyhelmithes) remains to be determined. Finally, a
      general secondary structure model of ITS2 for Calciodinelloideae (and other
      dinoflagellates) is reconstructed. Based on the 5.8S rRNA-28S rRNA interaction,
      it consists of a closed multibranch loop, with four major helices. At least helix
      III and IV have homology with paired regions found in other eukaryotic taxa (e.g.
      yeast, green algae and vertebrates). Since the secondary structures of both ITS
      regions are more conserved than the nucleotide sequences, their analysis helps in
      understanding molecular evolution and increases the number of structural
      characters. Thus, the structure models developed in this study may be generally
      useful for future phylogenetic analyses.

PMID- 14722226
TI  - A real-time PCR assay for DNA-methylation using methylation-specific blockers.
AB  - DNA methylation-based biomarkers have been discovered that could potentially be
      used for the diagnosis of cancer by detection of circulating, tumor-derived DNA
      in bodily fluids. Any methylation detection assay that would be applied to these
      samples must be capable of detecting small amounts of tumor DNA in the presence
      of background normal DNA. We have developed a real-time PCR assay, called
      HeavyMethyl, that is well suited for this application. HeavyMethyl uses
      methylation-specific oligonucleotide blockers and a methylation-specific probe to
      achieve methylation-specific amplification and detection. We tested the assays on
      unmethylated and artificially methylated DNA in order to determine the limit of
      detection. After careful optimization, our glutathione-S-transferase pi1 and
      Calcitonin assays can amplify as little as 30 and 60 pg of methylated DNA,
      respectively, and neither assay amplifies unmethylated DNA. The Calcitonin assay
      showed a highly significant methylation difference between normal colon and colon
      adenocarcinomas, and methylation was also detected in serum DNA from colon cancer
      patients. These assays show that HeavyMethyl technology can be successfully
      employed for the analysis of very low concentrations of methylated DNA, e.g. in
      serum of patients with tumors.

PMID- 14722227
TI  - Biological detection of low radiation doses by combining results of two
      microarray analysis methods.
AB  - The accurate determination of the biological effects of low doses of pollutants
      is a major public health challenge. DNA microarrays are a powerful tool for
      investigating small intracellular changes. However, the inherent low reliability
      of this technique, the small number of replicates and the lack of suitable
      statistical methods for the analysis of such a large number of attributes (genes)
      impair accurate data interpretation. To overcome this problem, we combined
      results of two independent analysis methods (ANOVA and RELIEF). We applied this
      analysis protocol to compare gene expression patterns in Saccharomyces cerevisiae
      growing in the absence and continuous presence of varying low doses of radiation.
      Global distribution analysis highlights the importance of mitochondrial membrane
      functions in the response. We demonstrate that microarrays detect cellular
      changes induced by irradiation at doses that are 1000-fold lower than the minimal
      dose associated with mutagenic effects.

PMID- 14722228
TI  - Revised UV extinction coefficients for nucleoside-5'-monophosphates and unpaired
      DNA and RNA.
AB  - Ultraviolet absorption provides the nearly universal basis for determining
      concentrations of nucleic acids. Values for the UV extinction coefficients of DNA
      and RNA rely on the mononucleotide values determined 30-50 years ago. We show
      that nearly all of the previously published extinction coefficients for the
      nucleoside-5'-monophosphates are too large, and in error by as much as 7%.
      Concentrations based on complete hydrolysis and the older set of values are too
      low by approximately 4% for typical RNA and 2-3% for typical DNA samples. We also
      analyzed data in the literature for the extinction coefficients of unpaired DNA
      oligomers. Robust prediction of concentrations can be made using 38 microg/A260
      unit for single-stranded DNA (ssDNA) having non-repetitive sequences and 40-80%
      GC. This is superior to currently used predictions that account for nearest
      neighbor frequency or base composition. The latter result in concentrations that
      are 10-30% too low for typical ssDNA used as primers for PCR and other similar
      techniques. Methods are described here to accurately measure concentrations of
      nucleotides by nuclear magnetic resonance. NMR can be used to accurately
      determine concentrations (and extinction coefficients) of biomolecules within 1%.

PMID- 14722230
TI  - Efficacy as a vector: the relative prevalence and paucity of inverse agonism.
AB  - This article describes the expected phenotypic behavior of all types of ligands
      in constitutively active receptor systems and, in particular, the molecular
      mechanisms of inverse agonism. The possible physiological relevance of inverse
      agonism also is discussed. Competitive antagonists with the molecular property of
      negative efficacy demonstrate inverse agonism in constitutively active receptor
      systems. This is a phenotypic behavior that can only be observed in the
      appropriate assay; a lack of observed inverse agonism is evidence that the ligand
      does not possess negative efficacy only if it can be shown that constitutive
      receptor activity is present. In the absence of constitutive activity, inverse
      agonists behave as simple competitive antagonists. A survey of 105 articles on
      the activity of 380 antagonists on 73 biological G-protein-coupled receptor
      targets indicates that, in this sample dataset, 322 are inverse agonists and 58
      (15%) are neutral antagonists. The predominance of inverse agonism agrees with
      theoretical predictions which indicate that neutral antagonists are the minority
      species in pharmacological space.

PMID- 14722231
TI  - More hints on Wnts: gene profiling by beta2-adrenergic receptor-frizzled
      chimeras.

PMID- 14722232
TI  - Unravelling green tea's mechanisms of action: more than meets the eye.

PMID- 14722233
TI  - Limited gene activation in tumor and normal epithelial cells treated with the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine.
AB  - It remains unclear to what extent drugs targeting transcriptional repressor
      complexes affect global gene expression in cells derived from target and
      nontarget human tissues. To address this question, we used genome-wide expression
      analysis using microarrays to analyze the response of three tumor and one normal
      epithelial cell line to treatment with the DNA methyltransferase inhibitor 5-aza
      2'-deoxycytidine (5-aza-CdR). Notably, we found that 5-aza-CdR treatment induced
      a limited number of genes (mean, 0.67%; range, 0.17-1.8% of 25,940 genes
      screened) in each cell line tested. The majority of the gene expression changes
      that followed 5-aza-CdR treatment were conserved in tumor and normal cells,
      including genes that function in cell proliferation, differentiation, immune
      presentation, and cytokine signaling. In contrast, 5-aza-CdR treatment induced
      the expression of cancer-testis class tumor antigens only in tumor cell lines. To
      explain this tissue-specific response, we analyzed the mechanism of
      transcriptional regulation of the prototype member of this tumor antigen gene
      family, MAGE-1. Taken from our analysis of MAGE-1 gene regulation, we propose
      that 5-aza-CdR-mediated gene activation has two distinct requirements: 1) the
      reversal of promoter hypermethylation, and 2) the presence of transcriptional
      activators competent for the activation of hypomethylated target promoters. This
      latter requirement for gene activation by 5-aza-CdR is probably mediated by
      sequence-specific transcription factors and may account for the limited number of
      human genes induced by 5-aza-CdR treatment. This revised model for gene
      activation by 5-aza-CdR has important implications for the use of DNA
      methyltransferase inhibitors in clinical settings.

PMID- 14722234
TI  - Measurement of intermolecular distances for the natural agonist Peptide docked at
      the cholecystokinin receptor expressed in situ using fluorescence resonance
      energy transfer.
AB  - Fluorescence resonance energy transfer is a powerful biophysical technique used
      to analyze the structure of membrane proteins. Here, we used this tool to
      determine the distances between a distinct position within a docked agonist and a
      series of distinct sites within the intramembranous confluence of helices and
      extracellular loops of the cholecystokinin (CCK) receptor. Pseudo-wild-type CCK
      receptor constructs having single reactive cysteine residues inserted into each
      of these sites were developed. The experimental strategy included the use of the
      full agonist, Alexa488-CCK, bound to these receptors as donor, with Alexa568
      covalently bound to the specific sites within the CCK receptor as acceptor. Site
      labeling was achieved by derivatization of intact cells with a novel fluorescent
      methanethiosulfonate reagent. A high degree of spectral overlap was observed
      between receptor-bound donor and receptor-derivatized acceptors, with no transfer
      observed for a series of controls representing saturation of the receptor binding
      site with nonfluorescent ligand and use of a null-reactive CCK receptor
      construct. The measured distances between the fluorophore within the docked
      agonist and the sites within the first (residue 102) and third (residue 341)
      extracellular loops of the receptor were shorter than those directed to the
      second loop (residue 204) or to intramembranous helix two (residue 94). These
      distances were accommodated well within a refined molecular model of the CCK
      occupied receptor that is fully consistent with all existing structure-activity
      and photoaffinity-labeling studies. This approach provides the initial insights
      into the conformation of extracellular loop regions of this receptor and
      establishes clear differences from analogous loops in the rhodopsin crystal
      structure.

PMID- 14722235
TI  - Identification of amino acids in rat pregnane X receptor that determine species
      specific activation.
AB  - The pregnane X receptor (PXR) is a nuclear receptor significantly involved in the
      transcriptional regulation of drug-metabolizing enzymes and transporters.
      Interestingly, certain PXR ligands such as rifampin have been shown to readily
      induce human and rabbit but not rodent members of the cytochrome P450 3A. Because
      drugs of divergent chemical structures seem to be similarly affected, we
      hypothesized that specific amino acid residue(s) or domains in rat PXR affect
      receptor activation by certain human PXR ligands. To identify such a domain(s),
      an array of human-rat and rat-human chimeric PXR cDNAs in a tandem head-to-tail
      configuration were created using a random chimeragenesis method. Pharmacological
      characterization of these chimeras revealed a discreet segment within the ligand
      binding domain of rat and human PXR to be essential for the rifampin effect.
      Within this region, the corresponding residues Leu308 and Phe305 of human and rat
      PXR, respectively, were found to be important for rifampin activation. Homology
      modeling derived from the recently determined crystal structure of human PXR
      indicates that these amino acids are located within or neighboring the flexible
      loop that forms part of the pore to the ligand-binding cavity. Rifampin,
      paclitaxel, and hyperforin sensitivity was conferred to rat PXR when Phe305 was
      converted to leucine, whereas attenuation of sensitivity was observed when Leu308
      of human PXR was replaced with phenylalanine. Accordingly, our data provide
      compelling new insight into the importance of the amino acids comprising the pore
      to the ligand-binding cavity as a critical modulator of PXR response.

PMID- 14722236
TI  - Gene profiling of Frizzled-1 and Frizzled-2 signaling: expression of G-protein
      coupled receptor chimeras in mouse F9 teratocarcinoma embryonal cells.
AB  - Wnt-Frizzled signaling via heterotrimeric G-proteins controls various aspects of
      early development. Because Wnts may activate more than one Frizzled,
      understanding the downstream signaling mechanisms and target genes for Frizzled
      activation has been a challenge. We constructed functional, chimeric receptors
      with the ligand-binding and transmembrane segments from the beta2-adrenergic
      receptor and the cytoplasmic domains from either rat Frizzled-1 (Rfz1) or
      Frizzled-2 (Rfz2). Activation with beta-agonist enables stimulation of only a
      single Frizzled pathway and profiling of genes targeted by this Frizzled-specific
      approach. Genes activated in mouse totipotent F9 teratocarcinoma cells solely by
      activation of the Rfz1 chimera include Lefty1, STAM, JAB, Erk1, MyD118, Fcer Ig,
      and follistatin, genes implicated in development. Stimulation of Rfz2 chimera,
      but not Rfz1, leads to activation of a smaller set of genes, including those for
      REST/NRSF, Groucho, nucleophosmin, and Ubc4/5E2. Activation of either Rfz1- or
      Rfz2-specific chimera leads, in these totipotent stem cells, to some differential
      activation of a common set of genes, including those for Msx-1, Msx-2, CBP/P300
      associated factor, ephrin A3, and Nip-3. We demonstrate the utility of beta2
      adrenergic receptor-Frizzled chimeras to provide the tools with which to activate
      and to probe Frizzled-specific downstream signaling to gene activation.

PMID- 14722237
TI  - Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4
      dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular
      properties, interactions with brain nicotinic receptors, and brain penetration.
AB  - 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA; GTS-21), an
      Alzheimer's drug candidate, selectively stimulates alpha7 nicotinic acetylcholine
      receptors. It rapidly enters the brain after oral administration and enhances
      cognitive behavior. Less than 1% of orally administered DMXBA is recovered in the
      urine. We report the identification and characterization of the major phase I
      metabolites of this drug candidate. Three hydroxy metabolites were generated in
      vitro by hepatic microsomal O-dealkylation of the two methoxy substituents on the
      benzylidene ring. They were also found in plasma of rats after oral
      administration, but at significantly lower concentrations relative to the parent
      compound. The metabolites displayed similar binding affinities and partial
      agonist potencies at rat brain alpha7 receptors. However, each displayed a higher
      efficacy than DMXBA for stimulating rat and human alpha7 receptors. Like DMXBA,
      the metabolites were weak antagonists at alpha4beta2 receptors. The predicted
      conformations of the metabolites were nearly identical with that of DMXBA.
      Ionization of the tetrahydropyridyl nitrogen was essential for high-affinity
      binding of DMXBA to the alpha7 receptor. The hydroxy metabolites were much more
      polar than DMXBA, derived from their experimentally estimated octanol/water
      partition coefficients, and they entered the brain much less readily than DMXBA.
      Their contributions to the behavioral effects of orally administered DMXBA, if
      any, would probably be very small during short-term administration. Benzylidene
      anabaseines pharmacologically similar to the hydroxy metabolites, but which enter
      the brain more readily, may provide greater stimulation of alpha7 receptors in
      the whole organism.

PMID- 14722238
TI  - Defining the propofol binding site location on the GABAA receptor.
AB  - The GABAA receptor is a target of many general anesthetics. The low affinity of
      general anesthetics has complicated the search for the location of anesthetic
      binding sites. Attention has focused on two pairs of residues near the
      extracellular ends of the M2 and M3 membrane-spanning segments,
      alpha1Ser270/beta2Asn265 (15' M2) and alpha1Ala291/beta2Met286 (M3). In the 4-A
      resolution acetylcholine receptor structure, the aligned positions are separated
      by approximately 10 A. To determine whether these residues are part of a binding
      site for propofol, an intravenous anesthetic, we probed propofol's ability to
      protect cysteines substituted for these residues from modification by the
      sulfhydryl-specific reagent p-chloromercuribenzenesulfonate (pCMBS-). pCMBS-
      reacted with cysteines substituted at the four positions in the absence and
      presence of GABA. Because propofol binding induces conformational change in the
      GABAAreceptor, we needed to establish a reference state of the receptor to
      compare reaction rates in the absence and presence of propofol. We compared
      reaction rates in the presence of GABA with those in the presence of propofol
      +GABA. The GABA concentration was reduced to give a similar fraction of the
      maximal GABA current in both conditions. Propofol protected, in a concentration
      dependent manner, the cysteine substituted for beta2Met286 from reaction with
      pCMBS-. Propofol did not protect the cysteine substituted for the aligned alpha1
      subunit position or the 15' M2 segment Cys mutants in either subunit. We infer
      that propofol may bind near the extracellular end of the betasubunit M3 segment.

PMID- 14722239
TI  - Salvinal, a novel microtubule inhibitor isolated from Salvia miltiorrhizae Bunge
      (Danshen), with antimitotic activity in multidrug-sensitive and -resistant human
      tumor cells.
AB  - Aqueous extracts of Salvia miltiorrhizae Bunge have been extensively used in the
      treatment of cardiovascular disorders and cancer in Asia. Recently, a compound, 5
      (3-hydroxypropyl)-7-methoxy-2-(3'-methoxy-4'-hydroxyphenyl)-3
      benzo[b]furancarbaldehyde (salvinal), isolated from this plant showed inhibitory
      activity against tumor cell growth and induced apoptosis in human cancer cells.
      In the present study, we investigated the cytotoxic effect and mechanisms of
      action of salvinal in human cancer cell lines. Salvinal caused inhibition of cell
      growth (IC50 range, 4-17 microM) in a variety of human cancer cell lines. Flow
      cytometry analysis showed that salvinal treatment resulted in a concentration
      dependent accumulation of cells in the G(2)/M phase. We observed, using Hoechst
      33258 dye staining, that salvinal blocked the cell cycle in mitosis. In vitro and
      in vivo examinations showed that salvinal inhibited tubulin polymerization in a
      concentration-dependent manner. Immunocytochemical studies demonstrated that
      salvinal treatment caused the changes of cellular microtubule network, similar to
      the effect of colchicine. In addition, salvinal treatment resulted in
      upregulation of cyclin B1 levels, activation of Cdc2 kinase, and Cdc25c
      phosphorylation. Furthermore, elevation of levels of MPM-2 phosphoepitopes in
      salvinal-treated cells in a concentration-dependent manner was also observed.
      Similar to the effect of other antitubulin agent, hyperphosphorylation of Bcl-2,
      induction of DNA fragmentation and activation of caspase-3 activity occurred in
      salvinal-treated cells. In particular, salvinal exhibited similar inhibitory
      activity against parental KB, P-glycoprotein-overexpressing KB vin10 and KB taxol
      50 cells, and multidrug resistance-associated protein (MRP)-expressing etoposide
      resistant KB 7D cells. Taken together, our data demonstrate that salvinal
      inhibits tubulin polymerization, arrests cell cycle at mitosis, and induces
      apoptosis. Notably, Salvinal is a poor substrate for transport by P-glycoprotein
      and MRP. Salvinal may be useful in the treatment of human cancers, particularly
      in patients with drug resistance.

PMID- 14722240
TI  - Mechanism of HIV-1 integrase inhibition by styrylquinoline derivatives in vitro.
AB  - Styrylquinoline derivatives (SQ) efficiently inhibit the 3'-processing activity
      of integrase (IN) with IC50 values of between 0.5 and 5 microM. We studied the
      mechanism of action of these compounds in vitro. First, we used steady-state
      fluorescence anisotropy to assay the effects of the SQ derivatives on the
      formation of IN-viral DNA complexes independently of the catalytic process. The
      IC50 values obtained in activity and DNA-binding tests were similar, suggesting
      that the inhibition of 3'-processing can be fully explained by the prevention of
      IN-DNA recognition. SQ compounds act in a competitive manner, with Ki values of
      between 400 and 900 nM. In contrast, SQs did not inhibit 3'-processing when IN
      DNA complexes were preassembled. Computational docking followed or not by
      molecular dynamics using the catalytic core of HIV-1 IN suggested a competitive
      inhibition mechanism, which is consistent with our previous data obtained with
      the corresponding Rous sarcoma virus domain. Second, we used preassembled IN
      preprocessed DNA complexes to assay the potency of SQs against the strand
      transfer reaction, independently of 3'-processing. Inhibition occurred even if
      the efficiency was decreased by about 5- to 10-fold. Our results suggest that two
      inhibitor-binding modes exist: the first one prevents the binding of the viral
      DNA and then the two subsequent reactions (i.e., 3'-processing and strand
      transfer), whereas the second one prevents the binding of target DNA, thus
      inhibiting strand transfer. SQ derivatives have a higher affinity for the first
      site, in contrast to that observed for the diketo acids, which preferentially
      bind to the second one.

PMID- 14722241
TI  - Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on
      a high throughput microarray analysis.
AB  - Curcumin has been reported to exhibit anti-invasive and/or antimetastatic
      activities, but the mechanism remains unclear. In this study, microarray analysis
      of gene expression profiles were used to characterize the anti-invasive
      mechanisms of curcumin in highly invasive lung adenocarcinoma cells (CL1-5).
      Results showed that curcumin significantly reduces the invasive capacity of CL1-5
      cells in a concentration range far below its levels of cytotoxicity (20 microM)
      and that this anti-invasive effect was concentration dependent (10.17 +/- 0.76 x
      10(3) cells at 0 microM; 5.67 +/- 1.53 x 10(3) cells at 1 microM; 2.67 +/- 0.58 x
      10(3) cells at 5 microM; 1.15 +/- 1.03 x 10(3) cells at 10 microM; P < 0.05) in
      the Transwell cell culture chamber assay. Using microarray analysis, 81 genes
      were down-regulated and 71 genes were up-regulated after curcumin treatment.
      Below sublethal concentrations of curcumin (10 microM), several invasion-related
      genes were suppressed, including matrix metalloproteinase 14 (MMP14; 0.65-fold),
      neuronal cell adhesion molecule (0.54-fold), and integrins alpha6 (0.67-fold) and
      beta4 (0.63-fold). In addition, several heat-shock proteins (Hsp) [Hsp27 (2.78
      fold), Hsp70 (3.75-fold), and Hsp40-like protein (3.21-fold)] were induced by
      curcumin. Real-time quantitative reverse transcription-polymerase chain reaction,
      Western blotting, and immunohistochemistry confirmed these results in both RNA
      and protein levels. Curcumin (1 to 10 microM) reduced the MMP14 expression in
      both mRNA and protein levels and also inhibited the activity of MMP2, the down
      stream gelatinase of MMP14, by gelatin zymographic analysis. Based on these data,
      it can be concluded that curcumin might be an effective antimetastatic agent with
      a mechanism of anti-invasion via the regulation of certain gene expressions.

PMID- 14722242
TI  - Green tea inhibits human inducible nitric-oxide synthase expression by down
      regulating signal transducer and activator of transcription-1alpha activation.
AB  - Green tea has been reported to show anti-inflammatory properties because of its
      inhibitory effects on the expression of several pro-inflammatory genes. Because
      the inducible nitricoxide synthase (iNOS) plays an important role in chronic
      inflammatory diseases, we have focused our attention on the regulation of iNOS
      expression by green tea in two different human epithelial cell lines, alveolar
      A549/8 and colon DLD-1 cells. With the use of electrophoretic mobility shift
      assays, we found a green tea-mediated down-regulation of the DNA binding activity
      of the transcription factor signal transducer and activator of transcription
      1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of
      the STAT-1alpha DNA binding was shown to result from reduced tyrosine
      phosphorylation of the STAT-1alpha protein and not from antioxidative effects of
      the green tea extract. Green tea extract inhibited human iNOS expression in a
      concentration-dependent manner, quantified in terms of iNOS mRNA, iNOS protein,
      and nitric oxide production in both cell lines. This inhibitory effect of green
      tea resulted from transcriptional inhibition as shown in reporter gene
      experiments. These data suggest that green tea extracts may be promising at least
      as an auxiliary anti-inflammatory principle in chronic inflammatory diseases.

PMID- 14722243
TI  - Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate
      receptors requires Fyn protein tyrosine kinase but not DARPP-32.
AB  - Interactions between dopaminergic and glutamatergic systems in the striatum are
      thought to underlie both the symptoms and adverse effects of treatment of
      Parkinson's disease. We have previously reported that activation of the dopamine
      D1 receptor triggers a rapid redistribution of striatal N-methyl-d-aspartate
      (NMDA) receptors between intracellular and postsynaptic sub-cellular
      compartments. To unravel the signaling pathways underlying this trafficking, we
      studied mice with targeted disruptions of either the gene that encodes the
      dopamine- and cAMP-regulated phosphoprotein (DARPP-32), a potent and selective
      inhibitor of protein phosphatase-1, or the protein tyrosine kinase Fyn. In
      striatal tissue from DARPP-32-depleted mice, basal tyrosine and serine
      phosphorylation of striatal NMDA receptor subunits NR1, NR2A, and NR2B was
      normal, and activation of dopamine D1 receptors with the agonist SKF-82958 [(+/-)
      6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine]
      produced redistribution of NMDA receptors from vesicular compartments (P3 and
      LP2) to synaptosomal membranes (LP1). In the Fyn knockout mice, basal tyrosine
      phosphorylation of NR2A and NR2B was drastically reduced, whereas serine
      phosphorylation of these NMDA subunits was unchanged. In the Fyn knockout mice,
      the dopamine D1 receptor agonist failed to induce subcellular redistribution of
      NMDA receptors. In addition, Fyn-depleted mice lesioned with 6-hydroxydopamine
      also failed to exhibit l-DOPA-induced behavioral sensitization, but this may be
      caused, at least in part, by resistance of these mice to the neurotoxic lesion.
      These findings suggest a novel mechanism for the trafficking of striatal NMDA
      receptors by signaling pathways that are independent of DARPP-32 but require Fyn
      protein tyrosine kinase. Strategies that prevent NMDA receptor subcellular
      redistribution through inhibition of Fyn kinase may prove useful in the treatment
      of Parkinson's disease.

PMID- 14722244
TI  - The liver-selective nitric oxide donor O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium
      1,2-diolate (V-PYRRO/NO) protects HepG2 cells against cytochrome P450 2E1
      dependent toxicity.
AB  - HepG2 cells expressing CYP2E1 (E47 cells) are more susceptible to toxicity by
      arachidonic acid (AA) or after glutathione depletion with an inhibitor of
      glutamate-cysteine ligase, l-buthionine-(S,R)-sulfoximine (BSO), compared with
      control HepG2 cells (C34 cells). The ability of nitric oxide (NO) to protect
      against CYP2E1-dependent toxicity has not been evaluated. We therefore studied
      the ability of O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO),
      a liver-selective NO donor, to protect against CYP2E1-dependent toxicity and
      compared this with protection by chemical NO donors. E47 cells incubated with V
      PYRRO/NO produced NO, whereas C34 cells did not. Incubation of E47 cells with 50
      microM AA or 100 microM BSO for 2 days resulted in a 50% loss of cell viability.
      VPYRRO/NO (1 mM) blocked this toxicity of AA and BSO by a mechanism involving NO
      release via CYP2E1 metabolism of VPYRRO/NO. NO scavengers hemoglobin and 2-(4
      carboxophenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide blocked the
      protective effects of V-PYRRO/NO. V-PYRRO/NO inhibited CYP2E1 activity and
      production of reactive oxygen species, whereas hemoglobin prevented these events.
      AA and BSO induced lipid peroxidation and decreased mitochondrial membrane
      potential; both of these effects were blocked by V-PYRRO/NO. Unlike V-PYRRO/NO,
      the chemical donors spermine/NO and (S)-nitroso-N-acetylpenicillamine release NO
      directly when added to the medium; however, they could partially protect against
      the CYP2E1-dependent toxicity. These results suggest that VPYRRO/NO protects
      HepG2 cells against CYP2E1-dependent toxicity through inhibition of CYP2E1
      derived reactive oxygen species production and lipid peroxidation by the
      generated NO and that this compound may be valuable in protecting against CYP2E1
      dependent toxicity via liver P450-specific generation of NO.

PMID- 14722245
TI  - Heterogeneity of P2X receptors in sympathetic neurons: contribution of neuronal
      P2X1 receptors revealed using knockout mice.
AB  - P2X receptors are highly expressed throughout the nervous system, where ATP has
      been shown to be a neurotransmitter. The aim of this study was to characterize
      P2X receptor expression within sympathetic postganglionic neurons from the
      superior cervical ganglia. Reverse transcription-polymerase chain reaction showed
      the presence of mRNA for all P2X receptors, raising the possibility of multiple
      subunit expression within these ganglia. Whole-cell patch-clamp and calcium
      imaging studies revealed a heterogeneous population of P2X receptors in
      approximately 70% of neurons. We propose that the heterogeneity in properties
      could be caused by differential expression and/or subunit composition of the P2X
      receptor. The dominant phenotype was P2X2-like; neurons showed slow
      desensitization, sensitivity to antagonists, and a profile of ionic modulation
      that is characteristic of P2X2 receptors: potentiation by acidification and
      extracellular Zn2+ and attenuation by high extracellular Ca2+ and pH. A
      subpopulation of neurons (10-15%) were alpha,beta-methylene ATP (alpha,beta
      meATP) sensitive, and in neurons from P2X1 receptor-deficient mice the alpha,beta
      meATP response was reduced to 2% of all neurons, demonstrating a direct role for
      P2X1 subunits. Control alpha,beta-meATP responses were eliminated by high
      extracellular Ca(2+) and pH, indicating the presence of heteromeric channels
      incorporating the properties of P2X1 and P2X2 receptors. This study demonstrates
      that in neurons, the P2X1 receptor can contribute to the properties of
      heteromeric P2X receptors. Given the expression of P2X1 receptors in a range of
      neurons, it seems likely that regulation of the properties of P2X receptors by
      this subunit is more widespread.

PMID- 14722246
TI  - Proteinase-activated receptor-2: key role of amino-terminal dipeptide residues of
      the tethered ligand for receptor activation.
AB  - Tryptic cleavage of proteinase-activated receptor-2 (PAR2) causes the unmasking
      of a tethered receptor-activating sequence, S37LIGRLDTP. We sought to determine,
      in the amino-terminal sequence of the PAR2 tethered ligand, the key amino acid
      residues that are responsible for receptor activation. Using site-directed
      mutagenesis, nine PAR2 mutants with alanine substitutions in the first six amino
      acids of the tethered ligand, S37LIGRL42., were prepared: PAR2S37A, PAR2L38A,
      PAR2I39A, PAR2G40A, PAR2R41A, PAR2A37-38, PAR2A39-42, PAR2A37,39-42, and PAR2A37
      42, along with the reverse-sequence construct, PAR2L37S38. These mutants,
      together with wild-type PAR2(PAR2wt), were expressed in Kirsten virus-transformed
      rat kidney cells and were then assessed for receptor-mediated calcium signaling
      upon activation by trypsin and by receptor-activating peptides like SLIGRL-NH2.
      In addition, the release of the N-terminal receptor sequence that is cleaved from
      PAR2 by trypsin activation was monitored in the above cell lines using a site
      targeted anti-receptor antibody. All PAR2 constructs were activated by SL-NH2,
      and all mutated tethered ligand sequences were unmasked by trypsin. However,
      differential activation of the receptor by trypsin in these mutants was observed:
      PAR2 mutants PAR2A37-38 and PAR2L37S38, in which the first two amino-terminal
      tethered ligand residues (S37L38) are either changed to alanines or reversed,
      yielded little or no response to trypsin, nor did PAR2A37,39-42. However, trypsin
      activated all other constructs. We conclude that the amino-terminal tethered
      ligand dipeptide sequence S37L38 plays a major role in the activation of PAR2.

PMID- 14722247
TI  - Site within N-Methyl-D-aspartate receptor pore modulates channel gating.
AB  - N-methyl-d-aspartate-type glutamate receptors (NMDARs) are ligand-gated ion
      channels activated by coagonists glutamate and glycine. NMDARs play a critical
      role in synaptic plasticity and excitotoxicity, largely because of their high
      calcium permeability and slow deactivation and desensitization kinetics. NR1 is
      an obligate subunit in all NMDAR complexes, where it combines with NR2A, 2B, 2C,
      and/or 2D. NR1 binds glycine, and residue Asn598 in the re-entrant membrane loop
      M2 largely determines NMDAR calcium permeability. In contrast, NR2 subunits bind
      glutamate and contain regions that regulate receptor desensitization and
      deactivation. Here, we report that mutations of NR1(Asn598) in combination with
      wild-type NR2A, expressed in human embryonic kidney 293 cells, exhibit altered
      glycine-independent desensitization. In the absence of extracellular calcium,
      substitution of Arg for Asn598 (NR1R) slowed desensitization by 2- to 3-fold
      compared with wild-type NR1/NR2A, and glutamate-evoked peak current EC50 and
      deactivation rate were also affected. Replacement of Asn by Gln (NR1Q) produced
      two distinct rates of calcium- and glycine-independent desensitization. Moreover,
      in the presence of extracellular calcium, the voltage-dependent pore block by
      calcium for the NR1Q mutant mimicked the effects of the positively charged Arg at
      this site in NR1R on slowing desensitization and deactivation. A kinetic model of
      the NMDA receptor-channel suggests that these results can be explained by altered
      gating and not ligand binding. Our data increase understanding of the role that
      amino acids within the NMDAR pore play in channel gating.

PMID- 14722248
TI  - HES-1, a novel target gene for the aryl hydrocarbon receptor.
AB  - Known mainly for its role as a toxin sensor, the aryl hydrocarbon receptor (AhR)
      complex is also involved in homeostasis regulation and differentiation processes
      and activated by xenobiotic compounds like 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). Hairy and Enhancer of Split homolog-1 (HES-1) is a key regulator not only
      in differentiation, but also in the cell cycle, and we show here that HES-1 is a
      new target gene for AhR regulation. HES-1 is up-regulated by TCDD both at protein
      and mRNA levels in T47D human mammary carcinoma cells. Actinomycin D experiments
      have shown that the AhR-mediated up-regulation of HES-1 mRNA is caused by
      transcriptional activation of the HES-1 gene, and we have identified a functional
      AhR response element (XRE) at -48/-42 in the upstream regulatory region of human
      HES-1. The HES-1 protein down-regulates expression of its own gene, and the HES
      element overlaps the XRE. Our data indicate that HES-1 and the AhR complex
      compete for binding to the composite HES/XRE element. Also, we have previously
      shown that HES-1 is down-regulated by the estrogen receptor ligand 17beta
      estradiol (E2). Up-regulation of HES-1 expression is correlated with suppression
      of cell proliferation, and the E2-mediated down-regulation of HES-1 therefore
      increases cell proliferation. It is known that TCDD exerts antiestrogenic action
      in breast tissue both in vivo and in vitro. Our observation that both the
      estrogen receptor and AhR signaling pathways regulate HES-1, but with opposing
      effects, suggests the existence of a new pathway by which AhR represses E2
      signaling.

PMID- 14722249
TI  - Transcriptional regulation of CYP2B1 induction in primary rat hepatocyte
      cultures: repression by epidermal growth factor is mediated via a distal enhancer
      region.
AB  - Phenobarbital (PB) alters expression of numerous hepatic genes, including genes
      involved in xenobiotic metabolism. Phenobarbital-dependent induction of
      cytochrome P-450 2B1 (CYP2B1) is subject to regulation by cytokines [e.g., by
      epidermal growth factor (EGF)], hormones [e.g., by growth hormone (GH)], or the
      cellular redox status. To investigate mechanisms involved in regulation of CYP2B1
      transcription, we performed promoter activation studies using primary rat
      hepatocyte cultures transiently transfected with individual CYP2B1 promoter
      luciferase reporter gene constructs. The 2679-bp native 5'-flanking region of the
      CYP2B1 gene conferred reporter gene activation by PB and the potent PB-like
      inducer permethrin (PM). Furthermore, this region mediated EGF- and GH-dependent
      repression of gene activation by PB-like inducers. A wide promoter mapping
      strategy with constructs bearing internal CYP2B1 promoter deletions led to
      identification of a distal responsive CYP2B1 enhancer region at -2230 to -2170,
      encompassing the section equivalent to the 51-bp PB-responsive enhancer module
      situated in the distal mouse Cyp2b10-5'-flanking region. The distal CYP2B1
      enhancer region conferred gene activation by PM, repression of PM-dependent
      activation by EGF, and enhancement of activation by the antioxidant N
      acetylcysteine (NAC). Mutational analyses of the region at -2230 to -2170
      suggested that the mechanisms of PB-dependent induction of CYP2B1 and the
      modulating effects by EGF or NAC are closely related.

PMID- 14722250
TI  - Examination of the mechanism(s) involved in doxorubicin-mediated iron
      accumulation in ferritin: studies using metabolic inhibitors, protein synthesis
      inhibitors, and lysosomotropic agents.
AB  - Anthracyclines are potent anticancer agents, but their use is limited by
      cardiotoxicity at high cumulative doses. The mechanisms involved in anthracycline
      mediated cardiotoxicity are still poorly understood, but numerous investigations
      have indicated a role for iron in this process. Our previous studies using
      neoplastic and myocardial cells showed that anthracyclines inhibit iron
      mobilization from the iron storage protein, ferritin, resulting in marked
      accumulation of ferritin-iron. Although the process of ferritin-iron mobilization
      is little understood, catabolism of ferritin by lysosomes may be a likely
      mechanism. Because anthracyclines have been shown to accumulate in lysosomes,
      this latter organelle may be a potential target for these drugs. The present
      study demonstrated, using native polyacrylamide gel electrophoresis-59Fe
      autoradiography, that ferritin-59Fe mobilization is an energy-dependent process
      that also requires protein synthesis. Depression of lysosomal activity via the
      enzyme inhibitors E64d [(2S,3S)-trans-epoxysuccinyl-l-leucylamido-2-methylbutane
      ethyl ester] and leupeptin or the lysosomotropic agents ammonium chloride,
      chloroquine, and methylamine resulted in a 3- to 5-fold increase in 59Feferritin
      accumulation compared with control cells. In addition, the proteasome inhibitors
      N-benzoyloxycarbonyl (Z)-Leu-Leuleucinal (MG132) and lactacystin also
      significantly increased 59Fe-ferritin levels compared with control cells. These
      effects of lysosomotropic agents or inhibitors of lysosomal activity were
      comparable with that observed with the anthracycline doxorubicin. Collectively,
      our study indicates a role for lysosomes and proteasomes in ferritin-iron
      mobilization, and this pathway is dependent on metabolic energy and protein
      synthesis. Furthermore, the lysosome/proteasome pathway may be a novel
      anthracycline target, inhibiting iron mobilization from ferritin that is
      essential for vital iron-requiring processes such as DNA synthesis.

PMID- 14722251
TI  - Characterization of agonist stimulation of cAMP-dependent protein kinase and G
      protein-coupled receptor kinase phosphorylation of the beta2-adrenergic receptor
      using phosphoserine-specific antibodies.
AB  - Agonist-stimulated desensitization of the beta2-adrenergic receptor (beta2AR) is
      caused by both a potent cAMP-dependent protein kinase (PKA)-mediated
      phosphorylation and a less potent, occupancy-dependent, G protein-coupled
      receptor kinase (GRK)-mediated phosphorylation that leads to beta-arrestin
      binding and internalization. In this study the kinetics of phosphorylation of the
      third intracellular loop PKA site Ser262 and the putative C-tail GRK sites
      Ser355, Ser356 of the human beta2AR overexpressed in human embryonic kidney (HEK)
      293 cells were characterized using phosphoserine-specific antibodies. Specificity
      of the antibodies was shown by their lack of reactivity with mutant beta2ARs
      lacking the respective sites. In addition, overexpression of GRK2 and GRK5
      increased basal levels of phosphorylation of the GRK sites Ser355, Ser356 in both
      COS-7 and HEK 293 cells. Epinephrine, prostaglandin E1, and forskolin at maximum
      concentrations stimulated phosphorylation of the beta2AR PKA site (Ser262) by 4
      fold, whereas PMA stimulated it by 2-fold. Epinephrine stimulated PKA site
      phosphorylation with an EC50 of 20 to 40 pM. In contrast, epinephrine stimulated
      GRK site phosphorylation (Ser355,Ser356) with an EC50 of 200 nM (1-min
      treatments), which is more than 4000-fold higher relative to PKA site
      phosphorylation, consistent with an occupancy-driven process. After 10 to 30 min,
      the EC50 for epinephrine stimulation of GRK site phosphorylation was reduced to
      10 to 20 nM but was still approximately 200-fold greater than for the PKA site.
      The EC50 for internalization correlated with GRK site phosphorylation and showed
      a similar shift with time of epinephrine stimulation. The kinetics of epinephrine
      stimulated GRK site phosphorylation were not altered in a mutant of the beta2AR
      lacking the PKA consensus sites. The initial levels (2 min) of a range of agonist
      stimulated GRK site phosphorylations were correlated with their efficacy for
      activation of adenylyl cyclase, namely epinephrine > or = formoterol = fenoterol
      > terbutaline = zinterol = albuterol > salmeterol > dobutamine > or = ephedrine.
      However, after 20 to 30 min of treatment, agonists with intermediate strengths,
      such as albuterol and salmeterol, stimulate GRK site phosphorylations that are
      approximately equal to that produced by epinephrine, and the correlation breaks
      down. The GRK and PKA site antibodies were also effective in detecting
      phosphorylation of the endogenous beta2AR expressed in A431 human epidermoid
      carcinoma cells. To summarize, our results show a remarkable amplification of PKA
      site phosphorylation relative to the putative GRK site phosphorylation,
      heterologous stimulation of the PKA site phosphorylation, no dependence of GRK
      site phosphorylation on PKA sites, and a reasonable correlation of initial levels
      of GRK site phosphorylation with the strength of a range of agonists.

PMID- 14722252
TI  - Characterization of the human calcitonin gene-related peptide receptor subtypes
      associated with receptor activity-modifying proteins.
AB  - Coexpression of receptor activity-modifying proteins (RAMPs) with calcitonin
      receptor 2 (CTR2) or calcitonin receptor-like receptor (CRLR) leads to the
      formation of four functional heterodimeric receptors for human calcitonin gene
      related peptide (hCGRP). In this study, we transfected hCGRP receptors into human
      embryonic kidney 293 cells and examined their pharmacological profiles using
      three dominant-negative (DN) RAMP mutants and various hCGRPalpha analogs.
      Fluorescence-activated cell-sorting analysis revealed that their cotransfection
      with CTR2 induced cell surface expression of all three RAMPs, and the three
      CTR2/RAMP heterodimers mediated equivalent levels of cAMP production in response
      to hCGRPalpha that were approximately 50-fold greater than were seen with CTR2
      alone. By contrast, [Tyr0]hCGRPalpha binding and signaling were markedly weaker
      with CTR2/RAMP2 or -3 than with CTR2/RAMP1 or CRLR/RAMP1; likewise, 125I
      [His10]hCGRPalpha bound most potently to CTR2/RAMP1. When CTR2 was coexpressed
      with DN RAMP1 or -2, hCGRPalpha-evoked responses were similar to those seen with
      CTR2 alone, despite the expression of both CTR2 and DN RAMP at the cell surface.
      But coexpression of DN RAMP3 with CTR2 significantly diminished hCGRPalpha
      signaling compared with that seen with CTR2 alone, indicating that DN RAMP3 is
      able to function as a negative regulator of CTR2 function. Competition
      experiments showed the relative agonist sensitivity of the four receptors to be
      hCGRPalpha > [Tyr0]hCGRPalpha > [Cys(Et)2,7]hCGRPalpha > [Cys(ACM)2,7]hCGRPalpha.
      Of the linear analogs, [Cys(ACM)2,7]hCGRPalpha (ACM, acetylmethoxy) enhanced cAMP
      formation only via CTR2/RAMP1, whereas [Cys(Et2,7)]hCGRPalpha acted via
      CRLR/RAMP1 and somewhat less potently via CTR2/RAMP1. Thus, among the three CGRP8
      37-insensitive receptors, CTR2/RAMP1 is most sensitive to the two linear analogs,
      suggesting that it could be classified as a CGRP2 receptor. Moreover, the
      combined use of iodinated CGRPalpha analogs may be useful for defining the CGRP1
      receptor.

PMID- 14722253
TI  - Novel neuroprotective K+ channel inhibitor identified by high-throughput
      screening in yeast.
AB  - Discovery of K+ channel modulators is limited by low-throughput capacity of
      existing K+ channel assays. To enable high-throughput screening for novel
      pharmacological modulators of K+ channels, we developed an assay based on growth
      of yeast that functionally expresses mammalian Kir2.1 channels. Screening of
      10,000 small molecules from a combinatorial chemical library yielded 42 potential
      Kir2.1 inhibitors. One compound, 3-bicyclo[2.2.1]hept-2-yl-benzene-1,2-diol, was
      confirmed to inhibit K+ channels in patch-clamp measurements in mammalian cells
      with EC50 values of 60 and 1 microM for Kir2.1 and Kv2.1 channels, respectively.
      Inhibition of Kv2.1 channels decreased in the presence of the external pore
      blocker tetraethylammonium (TEA) and depended on a residue required for
      extracellular TEA action, suggesting that the identified compound targets the
      external mouth of the channel. Furthermore, at the nontoxic concentration of 3
      microM, the identified compound completely abolished in vitro neuronal apoptosis
      mediated by Kv2.1 channels. Therefore, yeast-based screening has identified a
      novel uncharged neuroprotective mammalian K+ channel inhibitor.

PMID- 14722254
TI  - Human acetyl CoA:arylamine N-acetyltransferase variants generated by random
      mutagenesis.
AB  - Acetyl CoA:arylamine N-acetyltransferase (NAT) enzymes catalyze the N-acetylation
      of aromatic amines and the O-acetylation of aryl hydroxylamines, reactions that
      govern the disposition and toxicity of many drugs and carcinogens. The human NAT
      genes and enzymes NAT1 and NAT2 are highly polymorphic and constitute one of the
      best studied examples of the genetic control of drug metabolism. Naturally
      occurring human NAT variants provide limited insight into the relationship
      between NAT amino acid sequence and enzyme activity. We have shown previously
      that the expression of recombinant NAT2 in bacterial tester strains results in
      greatly enhanced sensitivity to mutagenic nitroaromatic compounds (which are
      reduced to aryl hydroxylamines by bacterial enzymes). We hypothesized that random
      mutagenesis combined with rapid screening could be used to identify functionally
      significant amino acid residues in NAT enzymes. Pools of NAT2 variants were
      generated by polymerase chain reaction-mediated random mutagenesis of the
      complete coding sequence. Reversion induced by a NAT-dependent mutagen, 3-methyl
      2-nitroimidazo[4,5-f]quinoline, was used as the basis for screening these pools
      to identify variants with altered enzyme activity. Eighteen variants were
      characterized by quantitative mutagenicity assays and enzyme kinetic
      measurements. This approach can provide new insight into the biochemistry of
      enzymes involved in the metabolic activation of mutagens.

PMID- 14722255
TI  - The antileukemia drug 2-chloro-2'-deoxyadenosine: an intrinsic transcriptional
      antagonist.
AB  - The nucleoside analog 2-chloro-2'-deoxyadenosine (CldAdo; cladribine) is
      effective in the treatment of hairy cell leukemia and chronic lymphocytic
      leukemia. CldAdo is phosphorylated and incorporated into cellular DNA but is not
      an absolute chain terminator. We demonstrated by in vitro gel-shift assays that
      binding interactions of the human TATA box-binding protein (TBP) were disrupted
      on 2-chlorodeoxyadenosine monophosphate (CldAMP)-substituted TATA box consensus
      sequences. We hypothesized that human RNA polymerase II (pol II) transcriptional
      processes would therefore be affected by 2-chlorodeoxyadenosine triphosphate
      (CldATP) incorporation into a promoter TATA element. Double-stranded DNA
      templates containing the adenovirus major late promoter and coding sequences were
      enzymatically synthesized as control or with site-specific CldAMP residues,
      incubated with HeLa extract, and the synthesis of radiolabeled 44-base
      transcripts was assessed. With increasing amounts of HeLa extract, CldAMP
      substitution for dAMP within the TATA box decreased in vitro pol II transcription
      by approximately 35% compared with control substrates. Time-course studies showed
      that transcript production increased in a linear fashion on control substrates.
      In contrast, transcription on CldAMP-substituted TATA sequences reached a plateau
      after 20 min. Furthermore, CldAMP-substituted promoter sequences trapped or
      sequestered TBP, preventing its dissociation from DNA and subsequent binding to
      additional TATA elements to reinitiate transcription. CldAdo thus represents the
      first example of a nucleoside analog that acts as a transcriptional antagonist.
      CldATP incorporation into gene regulatory sequences may provide a novel strategy
      to modulate specific protein/DNA interactions.

PMID- 14722256
TI  - Quantitative effects on c-Jun N-terminal protein kinase signaling determine
      synergistic interaction of cisplatin and 17-allylamino-17-demethoxygeldanamycin
      in colon cancer cell lines.
AB  - We investigated the effects of cisplatin and the hsp90 inhibitor 17-allylamino-17
      demethoxygeldanamycin (17-AAG) in combination in a panel of human colon
      adenocarcinoma cell lines that differ in their p53 and mismatch repair status.
      Analysis of cytotoxicity after combined treatment revealed additive effects of
      cisplatin and 17-AAG in the HCT 116, DLD1, and SW480 cell lines and antagonism in
      HT-29 cells. Clonogenic assays demonstrated antagonism in HT-29, an additive
      effect in SW480, and synergism in HCT 116 and DLD1 cell lines. Analysis of
      signaling pathways revealed that cisplatin-induced activation of c-Jun N-terminal
      kinase (JNK) was fully blocked by 17-AAG in HT-29 and SW480 cells, whereas in HCT
      116 and DLD1 cells it was inhibited only partially. The activation of caspases
      was also more pronounced in DLD1 and HCT 116 cell lines. These data suggested
      that a minimal level of apoptotic signaling through JNK was required for
      synergism with this combination. To test this hypothesis, we used the specific
      JNK inhibitor SP600125; when JNK was inhibited pharmacologically in HCT 116 and
      DLD1 cells, they demonstrated increased survival in clonogenic assays.
      Alternatively, sustained activation of JNK pathway led to an increase of the
      cytotoxicity of the cisplatin/17-AAG combination in HT-29 cells. Taken together,
      these data suggest that the synergistic interaction of this combination in colon
      cancer cell lines depends on the effect exerted by 17-AAG on cisplatin-induced
      signaling through JNK and associated pathways leading to cell death. An
      implication of that finding is that quantitative effects of signaling inhibitors
      may be critical for their ability to reverse cisplatin resistance.

PMID- 14722257
TI  - Susceptibility of feline immunodeficiency virus/human immunodeficiency virus type
      1 reverse transcriptase chimeras to non-nucleoside RT inhibitors.
AB  - To map the determinants of the lack of susceptibility of feline immunodeficiency
      virus (FIV) reverse transcriptase (RT) to anti human immunodeficiency virus type
      1 (HIV-1) non-nucleoside RT inhibitors (NNRTIs), a variety of chimeric HIV-1/FIV
      RTs were constructed. The majority of chimeric RTs had an affinity (Km) for their
      natural substrates comparable with that of the wild-type HIV-1 and FIV RTs, but
      their catalytic efficacy was decreased. Whereas HIV-1 RT could be made entirely
      insensitive to NNRTIs by exchanging the amino acid sequence 97 through 205 of FIV
      RT, none of the reverse FIV/HIV-1 RT chimeras gained susceptibility to NNRTIs.
      The amino acids that are thought to be involved in NNRTI susceptibility and that
      are different from those in HIV-1 RT have also been introduced in FIV RT. These
      mutant RTs gained virtually no susceptibility to efavirenz or capravirine. Vice
      versa, when these HIV-1-specific amino acids were replaced by their FIV RT
      counterparts in HIV-1 RT, susceptibility to the NNRTIs was lost. Thus, replacing
      segments or substituting relevant amino acids in FIV RT by their HIV-1 RT
      counterparts did not suffice to make FIV RT sensitive toward NNRTIs and was often
      accompanied by a decrease or even total loss of polymerase activity. It is
      postulated that, in contrast to the results found for HIV-1/HIV-2 RT chimeras and
      supported by the crystal structure of HIV-2 RT, there exist significant
      differences in the structure and/or flexibility of FIV RTs that may prevent
      NNRTIs from interacting with the FIV RT.

PMID- 14722258
TI  - RNA editing of the human serotonin 5-HT2C receptor disrupts transactivation of
      the small G-protein RhoA.
AB  - The human serotonin 5-HT2C receptor undergoes adenosineto-inosine RNA editing at
      five positions, generating multiple receptor isoforms with altered G-protein
      coupling properties. In the current study, we demonstrate that RNA editing
      regulates the pattern of intracellular signaling. The non-edited human 5-HT2C
      receptor isoform INI activates phospholipase D via the G13 heterotrimer G
      protein. We present evidence that transactivation of the small G-protein RhoA is
      required for phospholipase D activation. In contrast, neither transactivation of
      RhoA nor phospholipase D activation was detected in cells expressing the fully
      edited VGV isoform. The ability to activate phospholipase C is also reduced in
      VGV-expressing cells, but not to the extent found for the phospholipase D signal.
      We conclude that RNA editing represents a novel mechanism for regulating 5-HT2C
      receptor signaling to pathways linked to actin cytoskeletal organization and
      regulated exocytosis.

PMID- 14722259
TI  - Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor
      subtype selectivity via cooperativity rather than affinity.
AB  - Thiochrome (2,7-dimethyl-5H-thiachromine-8-ethanol), an oxidation product and
      metabolite of thiamine, has little effect on the equilibrium binding of l-[3H]N
      methyl scopolamine ([3H]NMS) to the five human muscarinic receptor subtypes (M1
      M5) at concentrations up to 0.3 mM. In contrast, it inhibits [3H]NMS dissociation
      from M1 to M4 receptors at submillimolar concentrations and from M5 receptors at
      1 mM. These results suggest that thiochrome binds allosterically to muscarinic
      receptors and has approximately neutral cooperativity with [3H]NMS at M1 to M4
      and possibly M5 receptors. Thiochrome increases the affinity of acetylcholine
      (ACh) 3- to 5-fold for inhibiting [3H]NMS binding to M4 receptors but has no
      effect on ACh affinity at M1 to M3 or M5 receptors. Thiochrome (0.1 mM) also
      increases the direct binding of [3H]ACh to M4 receptors but decreases it slightly
      at M2 receptors. In agreement with the binding data, thiochrome does not affect
      the potency of ACh for stimulating the binding of guanosine 5'-O-(3
      [35S]thiotriphosphate) ([35S]GTPgammaS) to membranes containing M1 to M3
      receptors, but it increases ACh potency 3.5-fold at M4 receptors. It also
      selectively reduces the release of [3H]ACh from potassium-stimulated slices of
      rat striatum, which contain autoinhibitory presynaptic M4 receptors, but not from
      hippocampal slices, which contain presynaptic M2 receptors. We conclude that
      thiochrome is a selective M4 muscarinic receptor enhancer of ACh affinity and has
      neutral cooperativity with ACh at M1 to M3 receptors; it therefore demonstrates a
      powerful new form of selectivity, "absolute subtype selectivity", which is
      derived from cooperativity rather than from affinity.

PMID- 14722260
TI  - A proteome analysis of the subcutaneous gel in avian hatchlings.
AB  - An appropriate level of water loss from eggs is critical to successful hatching.
      This water may be lost from the egg by evaporation, but where water loss is
      suboptimal, it is commonly observed that the hatchlings contain substantial
      amounts of a subcutaneous gel-like fluid. To characterize this fluid, we have
      analyzed the proteins that are contained within it. The protein complement
      comprised a small number of proteins in high concentrations. Proteomics analysis
      of the constituent proteins identified virtually all of these abundant proteins
      and confirmed that the subcutaneous gel was very similar in protein composition
      to plasma. However, the subcutaneous gel was substantially depleted of
      fibrinogen. It is possible that activation of the final stages of the coagulation
      process might account for the enhanced viscosity, creating a gel-like material
      that is relatively immobile in the subcutaneous space. This gel may function as a
      water volume that is partitioned during embryonic development in order to
      mitigate the effects of high water content of the egg caused by low mass loss
      during incubation and in some instances might also function as a water reserve to
      support the hatchling in the first few hours of life free of the shell.

PMID- 14722261
TI  - Herpes simplex virus virion host shutoff protein: immune evasion mediated by a
      viral RNase?

PMID- 14722262
TI  - The membrane-proximal tyrosine-based sorting signal of human immunodeficiency
      virus type 1 gp41 is required for optimal viral infectivity.
AB  - The membrane-proximal tyrosine-based sorting motif in the cytoplasmic domain of
      the human immunodeficiency virus type 1 Env glycoprotein is important for
      endocytosis from the plasma membrane, basolateral targeting of viral budding in
      polarized epithelial cells, and polarized budding from a localized region of the
      lymphocyte plasma membrane. To study the role of the Env sorting motif (Y712XXL)
      in infectivity, the incorporation of Env into virions, and viral entry, we
      disrupted the motif with a tyrosine-to-alanine substitution. To investigate the
      relationship between the Env sorting motif and the enhancement of infectivity by
      Nef, the EnvY712A substitution was made in both Nef-positive and Nef-negative
      backgrounds. In spreading infections, including those using primary lymphocytes,
      the growth of the Y712A mutant was as impaired as Nef-negative virus, and the
      EnvY712A/Delta-Nef combination mutant was almost completely defective. In single
      round infections using CD4-positive HeLa cells, the EnvY712A mutation impaired
      infectivity, and Nef retained the ability to enhance the infectivity in the
      context of EnvY712A. EnvY712 and Nef were required for the optimal infectivity of
      virions produced from either HEK293T or MT4 cells, but these sequences were
      required for the optimal incorporation of Env only when virions were produced
      from MT4 cells. Despite the wild-type levels of Env in viruses produced from 293T
      cells, the entry of the EnvY712A and Delta-Nef mutants into target cells was
      impaired. We conclude that the membrane-proximal tyrosine-based sorting motif of
      gp41 Env is, like Nef, important for optimal viral infectivity and, in the case
      of MT4 T cells, virion incorporation of Env. Nef does not require the Y712XXL
      motif to enhance viral infectivity. The finding that EnvY712 and Nef each affect
      the efficiency of viral entry independently of the Env content of virions
      suggests that both viral proteins are involved in trafficking events that
      influence morphogenesis to produce maximally fusogenic virus.

PMID- 14722263
TI  - Simian immunodeficiency virus promoter exchange results in a highly attenuated
      strain that protects against uncloned challenge virus.
AB  - Among the many simian immunodeficiency virus (SIV) immunogens, only live
      attenuated viral vaccines have afforded strong protection to a natural pathogenic
      isolate. Since the promoter is crucial to the tempo of viral replication in
      general, it was reasoned that promoter exchange might confer a novel means of
      attenuating SIV. The core enhancer and promoter sequences of the SIV macaque
      239nefstop strain (NF-kappaB/Sp1 region from -114 bp to mRNA start) have been
      exchanged for those of the human cytomegalovirus immediate-early promoter (CMV
      IE; from -525 bp to mRNA start). During culture of the resulting virus, referred
      to as SIVmegalo, on CEMx174 or rhesus macaque peripheral blood mononuclear cells,
      deletions arose in distal regions of the CMV-IE sequences that stabilized after 1
      or 2 months of culture. However, when the undeleted form of SIVmegalo was
      inoculated into rhesus macaques, animals showed highly controlled viremia during
      primary and persistent infection. Compared to parental virus infection in
      macaques, primary viremia was reduced by >1,000-fold to undetectable levels, with
      little sign of an increase of cycling cells in lymph nodes, CD4(+) depletion, or
      altered T-cell activation markers in peripheral blood. Moreover, in contrast to
      wild-type infection in most infected animals, the nef stop mutation did not
      revert to the wild-type codon, indicating yet again that replication was
      dramatically curtailed. Despite such drastic attenuation, antibody titers and
      enzyme-linked immunospot reactivity to SIV peptides, although slower to appear,
      were comparable to those seen in a parental virus infection. When animals were
      challenged intravenously at 4 or 6 months with the uncloned pathogenic SIVmac251
      strain, viremia was curtailed by approximately 1,000-fold at peak height without
      any sign of hyperactivation in CD4(+)- or CD8(+)-T-cell compartment or increase
      in lymph node cell cycling. To date, there has been a general inverse correlation
      between attenuation and protection; however, these findings show that promoter
      exchange constitutes a novel means to highly attenuate SIV while retaining the
      capacity to protect against challenge virus.

PMID- 14722264
TI  - Novel insect picorna-like virus identified in the brains of aggressive worker
      honeybees.
AB  - To identify candidate genes involved in the aggressive behavior of worker
      honeybees, we used the differential display method to search for RNAs exclusively
      detected in the brains of aggressive workers that had attacked a hornet. We
      identified a novel, 10,152-nucleotide RNA, termed Kakugo RNA. Kakugo RNA encodes
      a protein of 2,893 amino acid residues that shares structural features and
      sequence similarities with various picorna-like virus polyproteins, especially
      those from sacbrood virus, which infects honeybees. The Kakugo protein contains
      several domains that correspond to the virion protein, helicase, protease, and
      RNA-dependent RNA polymerase domains of various picorna-like virus polyproteins.
      When the worker bee tissue lysate was subjected to sucrose density gradient
      centrifugation, Kakugo RNA, except for the material at the bottom, was separated
      into two major peaks. One of the peaks corresponded to the position of Kakugo
      mRNA, and the other corresponded to the position of the poliovirus virion. These
      results suggest that the Kakugo RNA exists as an mRNA-like free RNA and virion
      RNA in the honeybee. Furthermore, injection of the lysate supernatant from the
      attacker heads into the heads of noninfected bees resulted in a marked increase
      in Kakugo RNA. These results demonstrate that Kakugo RNA is a plus-strand RNA of
      a novel picorna-like virus and that the brains of aggressive workers are infected
      by this novel virus. Kakugo RNA was detected in aggressive workers but not in
      nurse bees or foragers. In aggressive workers, Kakugo RNA was detected in the
      brain but not in the thorax or abdomen, indicating a close relation between viral
      infection in the brain and aggressive worker behaviors.

PMID- 14722265
TI  - A nonproliferating parvovirus vaccine vector elicits sustained, protective
      humoral immunity following a single intravenous or intranasal inoculation.
AB  - An ideal vaccine delivery system would elicit persistent protection following a
      single administration, preferably by a noninvasive route, and be safe even in the
      face of immunosuppression, either inherited or acquired, of the recipient. We
      have exploited the unique life cycle of the autonomous parvoviruses to develop a
      nonproliferating vaccine platform that appears to both induce priming and
      continually boost a protective immune response following a single inoculation. A
      crippled parvovirus vector was constructed, based on a chimera between minute
      virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface
      protein A (OspA) instead of its coat protein. The vector was packaged into an MVM
      lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a
      single vector dose, either intravenously or intranasally, elicited high-titer
      anti-OspA-specific antibody that provided protection from live spirochete
      challenge and was sustained over the lifetime of the animal. Both humoral and
      cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin
      G2a antibody and preferential gamma interferon production by OspA-specific CD4(+)
      T cells.

PMID- 14722266
TI  - Downregulation of major histocompatibility complex class I by human ubiquitin
      ligases related to viral immune evasion proteins.
AB  - Poxviruses and gamma-2 herpesviruses share the K3 family of viral immune evasion
      proteins that inhibit the surface expression of glycoproteins such as major
      histocompatibility complex class I (MHC-I), B7.2, ICAM-1, and CD95(Fas). K3
      family proteins contain an amino-terminal PHD/LAP or RING-CH domain followed by
      two transmembrane domains. To examine whether human homologues are functionally
      related to the viral immunoevasins, we studied seven membrane-associated RING-CH
      (MARCH) proteins. All MARCH proteins located to subcellular membranes, and
      several MARCH proteins reduced surface levels of known substrates of the viral K3
      family. Two closely related proteins, MARCH-IV and MARCH-IX, reduced surface
      expression of MHC-I molecules. In the presence of MARCH-IV or MARCH-IX, MHC-I was
      ubiquitinated and rapidly internalized by endocytosis, whereas MHC-I molecules
      lacking lysines in their cytoplasmic tail were resistant to downregulation. The
      amino-terminal regions containing the RING-CH domain of several MARCH proteins
      examined catalyzed multiubiquitin formation in vitro, suggesting that MARCH
      proteins are ubiquitin ligases. The functional similarity of the MARCH family and
      the K3 family suggests that the viral immune evasion proteins were derived from
      MARCH proteins, a novel family of transmembrane ubiquitin ligases that seems to
      target glycoproteins for lysosomal destruction via ubiquitination of the
      cytoplasmic tail.

PMID- 14722267
TI  - Nuclear localization but not PML protein is required for incorporation of the
      papillomavirus minor capsid protein L2 into virus-like particles.
AB  - Recent reports suggest that nuclear domain(s) 10 (ND10) is the site of
      papillomavirus morphogenesis. The viral genome replicates in or close to ND10. In
      addition, the minor capsid protein, L2, accumulates in these subnuclear
      structures and recruits the major capsid protein, L1. We have now used cell lines
      deficient for promyelocytic leukemia (PML) protein, the main structural component
      of ND10, to study the role of this nuclear protein for L2 incorporation into
      virus-like particles (VLPs). L2 expressed in PML protein knockout (PML(-/-))
      cells accumulated in nuclear dots, which resemble L2 aggregates forming at ND10
      in PML protein-containing cells. These L2 assemblies also attracted L1 and the
      transcriptional repressor Daxx, suggesting that they are functional in the
      absence of PML protein. In addition, L2-containing VLPs assembled in PML(-/-)
      cells. In order to analyze whether incorporation of L2 into VLPs requires any
      specific subcellular localization, an L1 mutant defective for nuclear transport
      and L2 mutants deficient in nuclear translocation and/or ND10 localization were
      constructed. Using this approach, we identified two independent L2 domains
      interacting with L1. Mutant L2 proteins not accumulating in ND10 were
      incorporated into VLPs. Mutant L1 protein, which assembled into VLPs in the
      cytoplasm, did not incorporate L2 defective for nuclear translocation. The same
      mutant L2 protein, which passively diffuses into the nucleus, is incorporated
      into wild-type L1-VLPs in the nucleus. Our data demonstrate that the
      incorporation of L2 into VLPs requires nuclear but not ND10 localization.

PMID- 14722268
TI  - Bunyamwera bunyavirus RNA synthesis requires cooperation of 3'- and 5'-terminal
      sequences.
AB  - Bunyamwera virus (BUNV) is the prototype of both the Orthobunyavirus genus and
      the Bunyaviridae family of segmented negative-sense RNA viruses. The tripartite
      BUNV genome consists of small (S), medium (M), and large (L) segments that are
      each transcribed to yield a single mRNA and are replicated to generate an
      antigenome that acts as a template for synthesis of further genomic strands. As
      for all negative-sense RNA viruses, the 3'- and 5'-terminal nontranslated regions
      (NTRs) of the BUNV S, M, and L segments exhibit nucleotide complementarity and,
      except for one conserved U-G pairing, this complementarity extends for 15, 18,
      and 19 nucleotides, respectively. We investigated whether the complementarity of
      3' and 5' NTRs reflected a functional requirement for terminal cooperation to
      promote BUNV RNA synthesis or, alternatively, was a consequence of genomic and
      antigenomic NTRs having similar functions requiring sequence conservation. We
      show that cooperation between 3'- and 5'-NTR sequences is required for BUNV RNA
      synthesis, and our results suggest that this cooperation is due to nucleotide
      complementarity allowing 3' and 5' NTRs to associate through base-pairing
      interactions. To examine the importance of complementarity in promoting BUNV RNA
      synthesis, we utilized a competitive replication assay able to examine the
      replication ability of all possible combinations of interacting nucleotides
      within a defined region of BUNV 3' and 5' NTRs. We show here that maximal RNA
      replication was signaled when sequences exhibiting perfect complementarity within
      3' and 5' NTRs were selected.

PMID- 14722269
TI  - Specific histone tail modification and not DNA methylation is a determinant of
      herpes simplex virus type 1 latent gene expression.
AB  - During herpes simplex virus type 1 (HSV-1) latency, gene expression is tightly
      repressed except for the latency-associated transcript (LAT). The mechanistic
      basis for this repression is unknown, but its global nature suggests regulation
      by an epigenetic mechanism such as DNA methylation. Previous work demonstrated
      that latent HSV-1 genomes are not extensively methylated, but these studies
      lacked the resolution to examine methylation of individual CpGs that could
      repress transcription from individual promoters during latency. To address this
      point, we employed established models to predict genomic regions with the highest
      probability of being methylated and, using bisulfite sequencing, analyzed the
      methylation profiles of these regions. We found no significant methylation of
      latent DNA isolated from mouse dorsal root ganglia in any of the regions
      examined, including the ICP4 and LAT promoters. This analysis indicates that
      methylation is unlikely to play a major role in regulating HSV-1 latent gene
      expression. Subsequently we focused on differential histone modification as
      another epigenetic mechanism that could regulate latent transcription. Chromatin
      immunoprecipitation analysis of the latent HSV-1 DNA repeat regions demonstrated
      that a portion of the LAT region is associated with histone H3 acetylated at
      lysines 9 and 14, consistent with a euchromatic and nonrepressed structure. In
      contrast, the chromatin associated with the HSV-1 DNA polymerase gene located in
      the unique long segment was not enriched in H3 acetylated at lysines 9 and 14,
      suggesting a transcriptionally inactive structure. These data suggest that
      histone composition may be a major regulatory determinant of HSV latency.

PMID- 14722270
TI  - Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central
      nervous system disease: protection from virus replication and antigen spread and
      selection of epitope escape mutants.
AB  - Both CD4(+) and CD8(+) T cells are required for clearance of the murine
      coronavirus mouse hepatitis virus (MHV) during acute infection. We investigated
      the effects of an epitope-specific CD8(+) T-cell response on acute infection of
      MHV, strain A59, in the murine CNS. Mice with CD8(+) T cells specific for gp33-41
      (an H-2D(b)-restricted CD8(+) T-cell epitope derived from lymphocytic
      choriomeningitis glycoprotein) were infected with a recombinant MHV-A59, also
      expressing gp33-41, as a fusion protein with enhanced green fluorescent protein
      (EGFP). By 5 days postinfection, these mice showed significantly (approximately
      20-fold) lower titers of infectious virus in the brain compared to control mice.
      Furthermore mice with gp33-41-specific CD8(+) cells exhibited much reduced levels
      of viral antigen in the brain as measured by immunohistochemistry using an
      antibody directed against viral nucleocapsid. More than 90% of the viruses
      recovered from brain lysates of such protected mice, at 5 days postinfection, had
      lost the ability to express EGFP and had deletions in their genomes encompassing
      EGFP and gp33-41. In addition, genomes of viruses from about half the plaques
      that retained the EGFP gene had mutations within the gp33-41 epitope. On the
      other hand, gp33-41-specific cells failed to protect perforin-deficient mice from
      infection by the recombinant MHV expressing gp33, indicating that perforin
      mediated mechanisms were needed. Virus recovered from perforin-deficient mice did
      not exhibit loss of EGFP expression and the gp33-41 epitope. These observations
      suggest that the cytotoxic T-cell response to gp33-41 exerts a strong immune
      pressure that quickly selects epitope escape mutants to gp33-41.

PMID- 14722271
TI  - T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo:
      implications for HIV pathogenesis.
AB  - Identification of T-cell subsets that are infected in vivo is essential to
      understanding the pathogenesis of human immunodeficiency virus (HIV) disease;
      however, this goal has been beset with technical challenges. Here, we used
      polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity,
      followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show
      that resting memory CD4(+) T cells are the predominantly infected cells but that
      terminally differentiated memory CD4(+) T cells contain 10-fold fewer copies of
      HIV DNA. Memory CD8(+) T cells can also be infected upon upregulation of CD4;
      however, this is infrequent and HIV-specific CD8(+) T cells are not infected
      preferentially. Naive CD4(+) T-cell infection is rare and principally confined to
      those peripheral T cells that have proliferated. Furthermore, the virus is
      essentially absent from naive CD8(+) T cells, suggesting that the thymus is not a
      major source of HIV-infected T cells in the periphery. These data illuminate the
      underlying mechanisms that distort T-cell homeostasis in HIV infection.

PMID- 14722272
TI  - Template sequence near the initiation nucleotide can modulate brome mosaic virus
      RNA accumulation in plant protoplasts.
AB  - Bromoviral templates for plus-strand RNA synthesis are rich in A or U nucleotides
      in comparison to templates for minus-strand RNA synthesis. Previous studies
      demonstrated that plus-strand RNA synthesis by the brome mosaic virus (BMV) RNA
      replicase is more efficient if the template contains an A/U-rich template
      sequence near the initiation site (K. Sivakumaran and C. C. Kao, J. Virol.
      73:6415-6423, 1999). These observations led us to examine the effects of
      nucleotide changes near the template's initiation site on the accumulation of BMV
      RNA3 genomic minus-strand, genomic plus-strand, and subgenomic RNAs in barley
      protoplasts transfected with wild-type and mutant BMV transcripts. Mutations in
      the template for minus-strand synthesis had only modest effects on BMV
      replication in barley protoplasts. Mutants with changes to the +3, +5, and +7
      template nucleotides accumulated minus-strand RNA at levels similar to the the
      wild-type level. However, mutations at positions adjacent to the initiation
      cytidylate in the templates for genomic and subgenomic plus-strand RNA synthesis
      significantly decreased RNA accumulation. For example, changes at the third
      template nucleotide for plus-strand RNA3 synthesis resulted in RNA accumulation
      at between 18 and 24% of the wild-type level, and mutations in the third template
      nucleotide for subgenomic RNA4 resulted in accumulations at between 7 and 14% of
      the wild-type level. The effects of the mutations generally decreased as the
      mutations occurred further from the initiation nucleotide. These findings
      demonstrate that there are different requirements of the template sequence near
      the initiation nucleotide for BMV RNA accumulation in plant cells.

PMID- 14722273
TI  - The immediate-early 63 protein of Varicella-Zoster virus: analysis of functional
      domains required for replication in vitro and for T-cell and skin tropism in the
      SCIDhu model in vivo.
AB  - The immediate-early 63-kDa (IE63) protein of varicella-zoster virus (VZV) is a
      phosphoprotein encoded by open reading frame (ORF) ORF63/ORF70. To identify
      functional domains, 22 ORF63 mutations were evaluated for effects on IE63 binding
      to the major VZV transactivator, IE62, and on IE63 phosphorylation and nuclear
      localization in transient transfections, and after insertion into the viral
      genome with VZV cosmids. The IE62 binding site was mapped to IE63 amino acids 55
      to 67, with R59/L60 being critical residues. Alanine substitutions within the
      IE63 center region showed that S165, S173, and S185 were phosphorylated by
      cellular kinases. Four mutations that changed two putative nuclear localization
      signal (NLS) sequences altered IE63 distribution to a cytoplasmic/nuclear
      pattern. Only three of 22 mutations in ORF63 were compatible with recovery of
      infectious VZV from our cosmids, but infectivity was restored by inserting intact
      ORF63 into each mutated cosmid. The viable IE63 mutants had a single alanine
      substitution, altering T171, S181, or S185. These mutants, rOKA/ORF63rev[T171],
      rOKA/ORF63rev[S181], and rOKA/ORF63rev[S185], produced less infectious virus and
      had a decreased plaque phenotype in vitro. ORF47 kinase protein and glycoprotein
      E (gE) synthesis was reduced, indicating that IE63 contributed to optimal
      expression of early and late gene products. The three IE63 mutants replicated in
      skin xenografts in the SCIDhu mouse model, but virulence was markedly attenuated.
      In contrast, infectivity in T-cell xenografts was not altered. Comparative
      analysis suggested that IE63 resembled the herpes simplex virus type 1 U(S)1.5
      protein, which is expressed colinearly with ICP22 (U(S)1). In summary, most
      mutations of ORF63 made with our VZV cosmid system were lethal for infectivity.
      The few IE63 changes that were tolerated resulted in VZV mutants with an impaired
      capacity to replicate in vitro. However, the IE63 mutants were attenuated in skin
      but not T cells in vivo, indicating that the contribution of the IE63
      tegument/regulatory protein to VZV pathogenesis depends upon the differentiated
      human cell type which is targeted for infection within the intact tissue
      microenvironment.

PMID- 14722274
TI  - Rapid production of neutralizing antibody leads to transient hepadnavirus
      infection.
AB  - Hepatitis B virus (HBV) frequently causes transient infections in adults but
      chronic infections in infants. The basis of these age-related outcomes is not
      known. Infection of ducks with duck hepatitis B virus (DHBV) displays a similar
      dependence of outcome on the age of the host at the time of infection. In this
      study we compared the infection of ducks at 3 days and 3 weeks of age. We found
      that the efficiency of infection of hepatocytes by virus in the inoculum was
      similar between the two age groups but that spread of the infection throughout
      the liver was severely inhibited in the 3-week-old-old ducks, while a rapid
      spread of the infection was observed in 3-day-old ducklings. Inhibition of virus
      spread was accompanied by the appearance in the serum of virus neutralizing
      activity, as assayed by blocking of infection of primary hepatocyte cultures.
      Neutralizing activity appeared as early as 1 or 2 days postinfection and
      increased during the next 2 weeks. Depletion of immunoglobulins from serum
      eliminated the neutralizing activity. The specific depletion of IgM indicated
      that IgM appeared as the dominant fraction of neutralizing antibody in the first
      2 days postinfection, but declined from day 3 on while IgG antibody rose. We
      conclude that excess neutralizing antibody arising rapidly in birds inoculated at
      3 weeks of age but not in newly hatched ducks prevented secondary cycles of
      infection, resulting in a limited infection in the liver and contributing to the
      eventual transient outcome of the infection.

PMID- 14722275
TI  - Human cytomegalovirus elicits a coordinated cellular antiviral response via
      envelope glycoprotein B.
AB  - Previous studies have shown that human cytomegalovirus (CMV) is a potent elicitor
      of interferon-stimulated gene (ISG) expression. Induction of the interferon
      pathway does not require replication-competent virus, and envelope glycoprotein B
      (gB) from CMV is a viral structural component that can directly induce
      transcription of ISGs. Here we extend these earlier findings by defining the
      consequences of inducing the interferon pathway. We found that cells respond to
      CMV or soluble gB by establishing a functional antiviral state within cell types
      critical in CMV biology, such as fibroblasts and endothelial cells. We have also
      discovered new insights into the mechanism by which the pathway is initiated.
      Interferon regulatory factor 3 (IRF3), a key transcriptional regulator of
      cellular interferon responses, is activated by CMV virions and soluble gB. Thus,
      IRF3 becomes activated via "outside-in" signal transduction events. This is a
      novel mechanism of activation of this key transcription factor by viruses. In
      comparison to soluble gB (gB(1-750)), which comprises the entire ectodomain of
      gB, a truncation mutant encompassing only the amino-terminal region of gB (gB(1
      460)) was markedly less effective at inducing antiviral responses. This indicates
      that the region of gB from residues 461 to 750 is important for initiation of the
      antiviral response. In addition, CMV and gB establish an antiviral state in
      alpha/beta interferon null cells, illustrating that primary induction of ISGs by
      CMV and gB is sufficient to establish the antiviral response and that interferon
      secretion is not necessary for the antiviral effect. Taken together, our findings
      reveal that CMV initiates a coordinated antiviral response through contact
      between gB and an as-yet-unidentified cell surface receptor(s).

PMID- 14722276
TI  - Borna disease virus multiplication in mouse organotypic slice cultures is site
      specifically inhibited by gamma interferon but not by interleukin-12.
AB  - Borna disease virus (BDV) induces a nonpurulent CD4- and CD8-T-cell-dependent
      meningoencephalitis in susceptible animals. Upon intracerebral infection, BDV
      replicates in the mouse central nervous system (CNS), but only a few mouse
      strains develop neurological disorder. The antiviral T cells appear to suppress
      BDV replication by a noncytolytic mechanism. Since BDV does not replicate in
      standard mouse cell cultures, the putative role of gamma interferon (IFN-gamma)
      in virus control could not be tested experimentally. Here, we report that mouse
      organotypic slice cultures can be used to elucidate the complex interactions of
      BDV, the CNS, and the immune system. We show that BDV replicated in various cell
      types of mouse cerebellar slice cultures in vitro. In infected slice cultures, a
      moderate upregulation of the chemokine genes CCL5 and CXCL10 was observed, while
      expression of various neural genes as well as other chemokine and cytokine genes
      was not altered. IFN-gamma inhibited the multiplication of BDV in cerebellar and
      hippocampal slice cultures in a dose-dependent manner. However, while complete
      suppression of BDV was observed in cerebellar slice cultures, inhibition was
      incomplete in hippocampal slice cultures. Kinetic studies indicated that IFN
      gamma protects noninfected cells from infection rather than clearing the virus
      from infected cells. These results demonstrate that BDV can replicate in cultured
      neural cells of the mouse if organ integrity is well preserved. They further show
      that IFN-gamma is a powerful inhibitor of BDV in the absence of blood-borne
      leukocytes in mouse cerebellar slice cultures.

PMID- 14722277
TI  - Transduction of bone-marrow-derived mesenchymal stem cells by using lentivirus
      vectors pseudotyped with modified RD114 envelope glycoproteins.
AB  - Bone-marrow-derived mesenchymal stem cells (MSCs) have attracted considerable
      attention as tools for the systemic delivery of therapeutic proteins in vivo, and
      the ability to efficiently transfer genes of interest into such cells would
      create a number of therapeutic opportunities. We have designed and tested a
      series of human immunodeficiency virus type 1 (HIV-1)-based vectors and vectors
      based on the oncogenic murine stem cell virus to deliver and express transgenes
      in human MSCs. These vectors were pseudotyped with either the vesicular
      stomatitis virus G (VSV-G) glycoprotein (GP) or the feline endogenous virus RD114
      envelope GP. Transduction efficiencies and transgene expression levels in MSCs
      were analyzed by quantitative flow cytometry and quantitative real-time PCR.
      While transduction efficiencies with virus particles pseudotyped with the VSV-G
      GP were found to be high, RD114 pseudotypes revealed transduction efficiencies
      that were 1 to 2 orders of magnitude below those observed with VSV-G pseudotypes.
      However, chimeric RD114 GPs, with the transmembrane and extracellular domains
      fused to the cytoplasmic domain derived from the amphotropic Moloney murine
      leukemia virus 4070A GP, revealed about 15-fold higher titers relative to the
      unmodified RD114 GP. The transduction efficiencies in human MSCs of HIV-1-based
      vectors pseudotyped with the chimeric RD114 GP were similar to those obtained
      with HIV-1 vectors pseudotyped with the VSV-G GP. Our results also indicate that
      RD114 pseudotypes were less toxic than VSV-G pseudotypes in human MSC progenitor
      assays. Taken together, these results suggest that lentivirus pseudotypes bearing
      alternative Env GPs provide efficient tools for ex vivo modification of human
      MSCs.

PMID- 14722278
TI  - A novel fluorescence resonance energy transfer assay demonstrates that the human
      immunodeficiency virus type 1 Pr55Gag I domain mediates Gag-Gag interactions.
AB  - Human immunodeficiency virus type 1 (HIV-1) assembly takes place at the plasma
      membrane of cells and is directed by the Pr55(Gag) polyprotein (Gag). One of the
      essential steps in the assembly process is the multimerization of Gag. We have
      developed a novel fluorescence resonance energy transfer (FRET) assay for the
      detection of protein-protein interactions between Gag molecules. We demonstrate
      that Gag multimerization takes place primarily on cellular membranes, with the
      majority of these interactions occurring on the plasma membrane. However,
      distinct sites of Gag-Gag interaction are also present at punctate intracellular
      locations. The I domain is a functional assembly domain within the nucleocapsid
      region of Gag that affects particle density, the subcellular localization of Gag,
      and the formation of detergent-resistant Gag protein complexes. Results from this
      study provide evidence that the I domain mediates Gag-Gag interactions. Using Gag
      fluorescent protein fusion constructs that were previously shown to define the
      minimal I domain within HIV-1 Pr55(Gag), we show by FRET techniques that protein
      protein interactions are greatly diminished when Gag proteins lacking the I
      domain are expressed. Gag-Tsg101 interactions are also seen in living cells and
      result in a shift of Tsg101 to the plasma membrane. The results within this study
      provide direct evidence that the I domain mediates protein-protein interactions
      between Gag molecules. Furthermore, this study establishes FRET as a powerful
      tool for the detection of protein-protein interactions involved in retrovirus
      assembly.

PMID- 14722279
TI  - Isolation of CD4-independent primary human immunodeficiency virus type 1 isolates
      that are syncytium inducing and acutely cytopathic for CD8+ lymphocytes.
AB  - Previous studies have established the existence of CD4-independent simian
      immunodeficiency virus, human immunodeficiency virus type 2 (HIV-2), and
      laboratory strains of HIV-1. However, whether CD4-independent viruses may also
      exist in HIV-1-infected patients has remained unclear. We have recently reported
      the isolation of viruses from an AIDS patient that were able to infect CD8(+)
      cells independent of CD4, using CD8 as a receptor. Using a similar approach, here
      we examined viruses from 12 randomly selected patients (obtained from the AIDS
      Research and Reference Program, National Institutes of Health) for the presence
      of CD4-independent HIV-1. CD4-independent variants were isolated from infected
      CD8(+) cells from the viral quasispecies of 7 of 12 patients. The CD4-independent
      isolates were able to infect primary CD8(+) cells as well as a CD4(-) CD8(+) T
      cell line. Soluble CD4 and blocking anti-CD4 or -CD8 antibody had no effect on
      infection of CD8(+) cells. Remarkably, two of the seven CD4-independent isolates,
      but not their parental bulk viruses, induced syncytia and caused acute death of
      infected CD8(+) cells. Some of the CD4-independent variants were also able to
      infect U87 cells that were negative for CD4, CD8, and common HIV coreceptors,
      suggesting a novel entry mechanism for these isolates. The CD4-independent
      isolates were derived from adults and children infected with subtypes A, B, and
      D. Although no common motif for CD4 independence was found, novel sequence
      changes were observed in critical areas of the envelopes of the CD4-independent
      viruses. These results demonstrate that HIV-1-infected patients can frequently
      harbor viruses that are able to mediate CD4-independent infection of CD8(+)
      cells. In addition, this study also provides evidence of primary HIV-1 variants
      that are syncytium inducing and acutely cytopathic for CD8(+) lymphocytes.

PMID- 14722280
TI  - Identification of host-specificity determinants in betanodaviruses by using
      reassortants between striped jack nervous necrosis virus and sevenband grouper
      nervous necrosis virus.
AB  - Betanodaviruses, the causal agents of viral nervous necrosis in marine fish, have
      bipartite positive-sense RNAs as genomes. The larger genomic segment, RNA1 (3.1
      kb), encodes an RNA-dependent RNA polymerase, and the smaller genomic segment,
      RNA2 (1.4 kb), codes for the coat protein. Betanodaviruses have marked host
      specificity, although the primary structures of the viral RNAs and encoded
      proteins are similar among betanodaviruses. However, no mechanism underlying the
      host specificity has yet been reported. To evaluate viral factors that control
      host specificity, we first constructed a cDNA-mediated infectious RNA
      transcription system for sevenband grouper nervous necrosis virus (SGNNV) in
      addition to that for striped jack nervous necrosis virus (SJNNV), which was
      previously established by us. We then tested two reassortants between SJNNV and
      SGNNV for infectivity in the host fish from which they originated. When striped
      jack and sevenband grouper larvae were bath challenged with the reassortant virus
      comprising SJNNV RNA1 and SGNNV RNA2, sevenband groupers were killed exclusively,
      similar to inoculation with SGNNV. Conversely, inoculations with the reassortant
      virus comprising SGNNV RNA1 and SJNNV RNA2 killed striped jacks but did not
      affect sevenband groupers. Immunofluorescence microscopic studies using anti
      SJNNV polyclonal antibodies revealed that both of the reassortants multiplied in
      the brains, spinal cords, and retinas of infected fish, similar to infections
      with parental virus inoculations. These results indicate that viral RNA2 and/or
      encoded coat protein controls host specificity in SJNNV and SGNNV.

PMID- 14722281
TI  - Heat shock protein 70 is related to thermal inhibition of nuclear export of the
      influenza virus ribonucleoprotein complex.
AB  - The influenza virus genome replicates and forms a viral ribonucleoprotein complex
      (vRNP) with nucleoprotein (NP) and RNA polymerases in the nuclei of host cells.
      vRNP is then exported into the cytoplasm for viral morphogenesis at the cell
      membrane. Matrix protein 1 (M1) and nonstructural protein 2/nuclear export
      protein (NS2/NEP) work in the nuclear export of vRNP by associating with it. It
      was previously reported that influenza virus production was inhibited in Madin
      Darby canine kidney (MDCK) cells cultured at 41 degrees C because nuclear export
      of vRNP was blocked by the dissociation of M1 from vRNP (A. Sakaguchi, E.
      Hirayama, A. Hiraki, Y. Ishida, and J. Kim, Virology 306:244-253, 2003). Previous
      data also suggested that a certain protein(s) synthesized only at 41 degrees C
      inhibited the association of M1 with vRNP. The potential of heat shock protein 70
      (HSP70) as a candidate obstructive protein was investigated. Induction of HSP70
      by prostaglandin A1 (PGA1) at 37 degrees C caused the suppression of virus
      production. The nuclear export of viral proteins was inhibited by PGA1, and M1
      was not associated with vRNP, indicating that HSP70 prevents M1 from binding to
      vRNP. An immunoprecipitation assay showed that HSP70 was bound to vRNP,
      suggesting that the interaction of HSP70 with vRNP is the reason for the
      dissociation of M1. Moreover, NS2 accumulated in the nucleoli of host cells
      cultured at 41 degrees C, showing that the export of NS2 was also disturbed at 41
      degrees C. However, NS2 was exported normally from the nucleus, irrespective of
      PGA1 treatment at 37 degrees C, suggesting that HSP70 does not influence NS2.

PMID- 14722282
TI  - Critical residues for GTP methylation and formation of the covalent m7GMP-enzyme
      intermediate in the capping enzyme domain of bamboo mosaic virus.
AB  - Open reading frame 1 of Bamboo mosaic virus (BaMV), a Potexvirus in the
      alphavirus-like superfamily, encodes a 155-kDa replicase responsible for the
      formation of the 5' cap structure and replication of the viral RNA genome. The N
      terminal domain of the viral replicase functions as an mRNA capping enzyme, which
      exhibits both GTP methyltransferase and S-adenosylmethionine (AdoMet)-dependent
      guanylyltransferase activities. We mutated each of the four conserved amino acids
      among the capping enzymes of members within alphavirus-like superfamily and a
      dozen of other residues to gain insight into the structure-function relationship
      of the viral enzyme. The mutant enzymes were purified and subsequently
      characterized. H68A, the mutant enzyme bearing a substitution at the conserved
      histidine residue, has an approximately 10-fold increase in GTP methyltransferase
      activity but completely loses the ability to form the covalent m(7)GMP-enzyme
      intermediate. High-pressure liquid chromatography analysis confirmed the
      production of m(7)GTP by the GTP methyltransferase activity of H68A. Furthermore,
      the produced m(7)GTP sustained the formation of the m(7)GMP-enzyme intermediate
      for the wild-type enzyme in the presence of S-adenosylhomocysteine (AdoHcy),
      suggesting that the previously observed AdoMet-dependent guanylation of the
      enzyme using GTP results from reactions of GTP methylation and subsequently
      guanylation of the enzyme using m(7)GTP. Mutations occurred at the other three
      conserved residues (D122, R125, and Y213), and H66 resulted in abolition of
      activities for both GTP methylation and formation of the covalent m(7)GMP-enzyme
      intermediate. Mutations of amino acids such as K121, C234, D310, W312, R316,
      K344, W406, and K409 decreased both activities by various degrees, and the
      extents of mutational effects follow similar trends. The affinity to AdoMet of
      the various BaMV capping enzymes, except H68A, was found in good correlations
      with not only the magnitude of GTP methyltransferase activity but also the
      capability of forming the m(7)GMP-enzyme intermediate. Taken together with the
      AdoHcy dependence of guanylation of the enzyme using m(7)GTP, a basic working
      mechanism, with the contents of critical roles played by the binding of
      AdoMet/AdoHcy, of the BaMV capping enzyme is proposed and discussed.

PMID- 14722283
TI  - Quinoline derivatives are therapeutic candidates for transmissible spongiform
      encephalopathies.
AB  - We previously reported that quinacrine inhibited the formation of an abnormal
      prion protein (PrPres), a key molecule in the pathogenesis of transmissible
      spongiform encephalopathy, or prion disease, in scrapie-infected neuroblastoma
      cells. To elucidate the structural aspects of its inhibiting action, various
      chemicals with a quinoline ring were screened in the present study. Assays of the
      scrapie-infected neuroblastoma cells revealed that chemicals with a side chain
      containing a quinuclidine ring at the 4 position of a quinoline ring (represented
      by quinine) inhibited the PrPres formation at a 50% inhibitory dose ranging from
      10(-1) to 10(1) micro M. On the other hand, chemicals with a side chain at the 2
      position of a quinoline ring (represented by 2,2'-biquinoline) more effectively
      inhibited the PrPres formation at a 50% inhibitory dose ranging from 10(-3) to
      10(-1) micro M. A metabolic labeling study revealed that the action of quinine or
      biquinoline was not due to any alteration in the biosynthesis or turnover of
      normal prion protein, whereas surface plasmon resonance analysis showed a strong
      binding affinity of biquinoline with a recombinant prion protein. In vivo studies
      revealed that 4-week intraventricular infusion of quinine or biquinoline was
      effective in prolonging the incubation period in experimental mouse models of
      intracerebral infection. The findings suggest that quinoline derivatives with a
      nitrogen-containing side chain have the potential of both inhibiting PrPres
      formation in vitro and prolonging the incubation period of infected animals.
      These chemicals are new candidates for therapeutic drugs for use in the treatment
      of transmissible spongiform encephalopathies.

PMID- 14722284
TI  - Specific inhibition of human cytomegalovirus glycoprotein B-mediated fusion by a
      novel thiourea small molecule.
AB  - A novel small molecule inhibitor of human cytomegalovirus (HCMV) was identified
      as the result of screening a chemical library by using a whole-virus infected
      cell assay. Synthetic chemistry efforts yielded the analog designated CFI02, a
      compound whose potency had been increased about 100-fold over an initial
      inhibitor. The inhibitory concentration of CFI02 in various assays is in the low
      nanomolar range. CFI02 is a selective and potent inhibitor of HCMV; it has no
      activity against other CMVs, alphaherpesviruses, or unrelated viruses. Mechanism
      of-action studies indicate that CFI02 acts very early in the replication cycle,
      inhibiting virion envelope fusion with the cell plasma membrane. Mutants
      resistant to CFI02 have mutations in the abundant virion envelope glycoprotein B
      that are sufficient to confer resistance. Taken together, the data suggest that
      CFI02 inhibits glycoprotein B-mediated HCMV virion fusion. Furthermore, CFI02
      inhibits the cell-cell spread of HCMV. This is the first study of a potent and
      selective small molecule inhibitor of CMV fusion and cell-cell spread.

PMID- 14722285
TI  - Fusion proteins consisting of human immunodeficiency virus type 1 integrase and
      the designed polydactyl zinc finger protein E2C direct integration of viral DNA
      into specific sites.
AB  - In order to establish a productive infection, a retrovirus must integrate the
      cDNA of its RNA genome into the host cell chromosome. While this critical process
      makes retroviruses an attractive vector for gene delivery, the nonspecific nature
      of integration presents inherent hazards and variations in gene expression. One
      approach to alleviating the problem involves fusing retroviral integrase to a
      sequence-specific DNA-binding protein that targets a defined chromosomal site. We
      prepared proteins consisting of wild-type or truncated human immunodeficiency
      virus type 1 (HIV-1) integrase fused to the synthetic polydactyl zinc finger
      protein E2C. The purified fusion proteins bound specifically to the 18-bp E2C
      recognition sequence as analyzed by DNase I footprinting. The fusion proteins
      were catalytically active and biased integration of retroviral DNA near the E2C
      binding site in vitro. The distribution was asymmetric, and the major integration
      hot spots were localized within a 20-bp region upstream of the C-rich strand of
      the E2C recognition sequence. Integration bias was not observed with target
      plasmids bearing a mutated E2C-binding site or when HIV-1 integrase and E2C were
      added to the reaction as separate proteins. The results demonstrate that the
      integrase-E2C fusion proteins offer an efficient approach and a versatile
      framework for directing the integration of retroviral DNA into a predetermined
      DNA site.

PMID- 14722286
TI  - The pseudorabies virus US3 protein is a component of primary and of mature
      virions.
AB  - Herpesviruses acquire a primary envelope by budding of capsids at the inner
      leaflet of the nuclear membrane. They then traverse into the cytoplasm after
      fusion of the primary envelope with the outer leaflet of the nuclear membrane. In
      the alphaherpesvirus pseudorabies virus (PrV), the latter process is impaired
      when the US3 protein is absent. Acquisition of final tegument and envelope occurs
      in the cytoplasm. Besides the capsid components, only the UL31 and UL34 gene
      products of PrV have unequivocally been shown to be part of primary enveloped
      virions, whereas they lack several tegument proteins present in mature virions
      (reviewed by T. C. Mettenleiter, J. Virol. 76:1537-1547, 2002). Using
      immunoelectron microscopy, we show that the US3 protein is present in primary
      enveloped as well as in mature virions. It is also detectable in intracytoplasmic
      inclusions produced in the absence of other viral tegument components or envelope
      associated glycoproteins. In particular, inclusions formed in the absence of the
      inner tegument protein UL37 contained the US3 protein. Thus, the US3 protein is a
      tegument component of both forms of enveloped alphaherpes virions. We hypothesize
      that US3 protein in primary virions modulates deenvelopment at the outer leaflet
      of the nuclear membrane and is either lost from primary virions during nuclear
      egress and subsequently reacquired early during tegumentation or is retained
      during transit of the nucleocapsid through the nuclear membrane.

PMID- 14722287
TI  - Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are
      major escape mechanisms from CTL immune pressure in human immunodeficiency virus
      type 1 infection.
AB  - Investigating escape mechanisms of human immunodeficiency virus type 1 (HIV-1)
      from cytotoxic T lymphocytes (CTLs) is essential for understanding the
      pathogenesis of HIV-1 infection and developing effective vaccines. To study the
      processing and presentation of known CTL epitopes, we prepared Epstein-Barr virus
      transformed B cells that endogenously express the gag gene of six field isolates
      by adopting an env/nef-deletion HIV-1 vector pseudotyped with vesicular
      stomatitis virus G protein and then tested them for the recognition by Gag
      epitope-specific CTL lines or clones. We observed that two field variants,
      SLFNTVAVL and SVYNTVATL, of an A*0201-restricted Gag CTL epitope SLYNTVATL, and
      three field variants, KYRLKHLVW, QYRLKHIVW, and RYRLKHLVW, of an A24-restricted
      Gag CTL epitope KYKLKHIVW escaped from being killed by the CTL lines, despite the
      fact that they were recognized when the synthetic peptides corresponding to these
      variant sequences were exogenously loaded onto the target cells. Thus, their
      escape is likely due to the changes that occur during the processing and
      presentation of epitopes in the infected cells. Mutations responsible for this
      mode of escape were located within the epitope regions rather than the flanking
      regions, and such mutations did not influence the virus replication. The results
      suggest that the impaired antigen processing and presentation often occur in HIV
      1 field isolates and thus are one of the major mechanisms that enable HIV-1 to
      escape from CTL recognition. We emphasize the importance of testing HIV-1
      variants in an endogenous expression system.

PMID- 14722288
TI  - Cytotoxic-T-lymphocyte human papillomavirus type 16 E5 peptide with CpG
      oligodeoxynucleotide can eliminate tumor growth in C57BL/6 mice.
AB  - Previously, we identified human papillomavirus type 16 (HPV-16) E5 as a tumor
      rejection antigen that can induce cytotoxic T lymphocytes (CTLs) to protect
      against tumor growth (D. W. Liu et al., J. Virol. 74:9083-9089, 2000). In the
      present study, we further mapped the CTL epitope of E5 protein by analyzing E5
      specific CD8(+) gamma interferon-positive (IFN-gamma(+)) double-positive cells in
      C57BL/6 mice with flow cytometry. The results showed the region spanning amino
      acids 25 to 33 (VCLLIRPLL) contained the potential D(b)-restricted CTL epitope.
      Subsequently, to determine whether peptide E5 25-33-based vaccination could
      induce E5-specific CTL activity, syngeneic animals received E5 25-33 emulsified
      with either CpG oligodeoxynucleotide (CpG ODN 1826) or Freund's adjuvant, and the
      growth of the tumors was monitored. The results showed that although both
      adjuvants induced E5-specific CD8(+) IFN-gamma(+) T cells and eradicated E5
      containing tumor growth, CpG ODN was found to stimulate stronger CTL response
      than Freund's adjuvant. We also compared the immune response of the
      effector/memory/recall phase induced by E5 25-33 peptide or by E5 protein that
      was synthesized in vivo by adenovirus-based E5 gene delivery. E5 25-33 peptide
      plus CpG ODN was shown to be a superior vaccine compared to the adenovirus-based
      E5 gene. Interestingly, their chronological patterns of immune response were
      similar, suggesting that E5 25-33 is a major CTL peptide of E5 protein.

PMID- 14722289
TI  - Cell-dependent role for the poliovirus 3' noncoding region in positive-strand RNA
      synthesis.
AB  - We previously reported the isolation of a mutant poliovirus lacking the entire
      genomic RNA 3' noncoding region. Infection of HeLa cell monolayers with this
      deletion mutant revealed only a minor defect in the levels of viral RNA
      replication. To further analyze the consequences of the genomic 3' noncoding
      region deletion, we examined viral RNA replication in a neuroblastoma cell line,
      SK-N-SH cells. The minor genomic RNA replication defect in HeLa cells was
      significantly exacerbated in the SK-N-SH cells, resulting in a decreased capacity
      for mutant virus growth. Analysis of the nature of the RNA replication deficiency
      revealed that deleting the poliovirus genomic 3' noncoding region resulted in a
      positive-strand RNA synthesis defect. The RNA replication deficiency in SK-N-SH
      cells was not due to a major defect in viral translation or viral protein
      processing. Neurovirulence of the mutant virus was determined in a transgenic
      mouse line expressing the human poliovirus receptor. Greater than 1,000 times
      more mutant virus was required to paralyze 50% of inoculated mice, compared to
      that with wild-type virus. These data suggest that, together with a cellular
      factor(s) that is limiting in neuronal cells, the poliovirus 3' noncoding region
      is involved in positive-strand synthesis during genome replication.

PMID- 14722290
TI  - A cis-acting replication element in the sequence encoding the NS5B RNA-dependent
      RNA polymerase is required for hepatitis C virus RNA replication.
AB  - RNA structures play key roles in the replication of RNA viruses. Sequence
      alignment software, thermodynamic RNA folding programs, and classical comparative
      phylogenetic analysis were used to build models of six RNA elements in the coding
      region of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, NS5B. The
      importance of five of these elements was evaluated by site-directed mutagenesis
      of a subgenomic HCV replicon. Mutations disrupting one of the predicted stem-loop
      structures, designated 5BSL3.2, blocked RNA replication, implicating it as an
      essential cis-acting replication element (CRE). 5BSL3.2 is about 50 bases in
      length and is part of a larger predicted cruciform structure (5BSL3). As
      confirmed by RNA structure probing, 5BSL3.2 consists of an 8-bp lower helix, a 6
      bp upper helix, a 12-base terminal loop, and an 8-base internal loop. Mutational
      analysis and structure probing were used to explore the importance of these
      features. Primary sequences in the loops were shown to be important for HCV RNA
      replication, and the upper helix appears to serve as an essential scaffold that
      helps maintain the overall RNA structure. Unlike certain picornavirus CREs, whose
      function is position independent, 5BSL3.2 function appears to be context
      dependent. Understanding the role of 5BSL3.2 and determining how this new CRE
      functions in the context of previously identified elements at the 5' and 3' ends
      of the RNA genome should provide new insights into HCV RNA replication.

PMID- 14722291
TI  - Quantification of the DNA cleavage and packaging proteins U(L)15 and U(L)28 in A
      and B capsids of herpes simplex virus type 1.
AB  - The proteins produced by the herpes simplex virus type 1 (HSV-1) genes U(L)15 and
      U(L)28 are believed to form part of the terminase enzyme, a protein complex
      essential for the cleavage of newly synthesized, concatameric herpesvirus DNA and
      the packaging of the resultant genome lengths into preformed capsids. This work
      describes the purification of recombinant forms of pU(L)15 and pU(L)28, which
      allowed the calculation of the average number of copies of each protein in A and
      B capsids and in capsids lacking the putative portal encoded by U(L)6. On
      average, 1.0 (+/-0.29 [standard deviation]) copies of pU(L)15 and 2.4 (+/-0.97)
      copies of pU(L)28 were present in B capsids, 1.2 (+/-0.72) copies of pU(L)15 and
      1.5 (+/-0.86) copies of pU(L)28 were found in mutant capsids lacking the putative
      portal protein pU(L)6, and approximately 12.0 (+/-5.63) copies of pU(L)15 and 0.6
      (+/-0.32) copies of pU(L)28 were present in each A capsid. These results suggest
      that the packaging machine is partly comprised of approximately 12 copies of
      pU(L)15, as found in A capsids, with wild-type B and mutant U(L)6(-) capsids
      containing an incomplete complement of cleavage and packaging proteins. These
      results are consistent with observations that B capsids form by default in the
      absence of packaging machinery in vitro and in vivo. In contrast, A capsids may
      be the result of initiated but aborted attempts at DNA packaging, resulting in
      the retention of at least part of the DNA packaging machinery.

PMID- 14722292
TI  - Compensatory link between fusion and endocytosis of human immunodeficiency virus
      type 1 in human CD4 T lymphocytes.
AB  - Virions of the type 1 human immunodeficiency virus (HIV-1) can enter target cells
      by fusion or endocytosis, with sharply different functional consequences. Fusion
      promotes productive infection of the target cell, while endocytosis generally
      leads to virion inactivation in acidified endosomes or degradation in lysosomes.
      Virion fusion and endocytosis occur equally in T cells, but these pathways have
      been regarded as independent because endocytosis of HIV virions requires neither
      CD4 nor CCR5/CXCR4 engagement in HeLa-CD4 cells. Using flow cytometric techniques
      to assess the binding and entry of green fluorescent protein (GFP)-Vpr-labeled
      HIV virions into primary peripheral blood mononuclear cells, we have found that
      HIV fusion and endocytosis are restricted to the CD4-expressing subset of cells
      and that both pathways commonly require the initial binding of HIV virions to
      surface CD4 receptors. Blockade of CXCR4-tropic HIV virion fusion with AMD3100, a
      CXCR4-specific entry inhibitor, increased virion entry via the endocytic pathway.
      Similarly, inhibition of endosome acidification with bafilomycin A1, concanamycin
      A, or NH(4)Cl enhanced entry via the fusion pathway. Although fusion remained
      dependent on CD4 and chemokine receptor binding, the endosome inhibitors did not
      alter surface expression of CD4 and CXCR4. These results suggest that fusion in
      the presence of the endosome inhibitors likely occurs within nonacidified
      endosomes. However, the ability of these inhibitors to impair vesicle trafficking
      from early to late endosomes in some cells could also increase the recycling of
      these virion-containing endosomes to the cell surface, where fusion occurs. In
      summary, our results reveal an unexpected, CD4-mediated reciprocal relationship
      between the pathways governing HIV virion fusion and endocytosis.

PMID- 14722293
TI  - Multiple modifications allow high-titer production of retroviral vectors carrying
      heterologous regulatory elements.
AB  - Tumor-specific expression of therapeutic genes is a prerequisite in many
      approaches to retrovirus-mediated cancer gene therapy. However, tissue
      specificity is often associated with a reduction in viral titer. To overcome this
      problem, we constructed a series of murine leukemia virus (MLV)-based retroviral
      promoter conversion (ProCon) vectors carrying either the simian virus 40 poly(A)
      signal trimer (3pA) inserted in the 3' long terminal repeat (LTR) of these
      vectors or the human cytomegalovirus enhancer region (CMVe) inserted 5' and 3' of
      the retroviral LTRs. Furthermore, an extended AT stretch/attachment site (AT/att)
      of wild-type MLV was introduced into the vector. In the vector-producing cells,
      insertion of the CMVe and/or the 3pA resulted in a three- to fourfold-enhanced
      marker gene expression compared to the parental vector, whereas insertion of the
      AT/att gave a slight decrease in expression. The combination of all three
      modifications had no additional effects. In contrast, however, neomycin selection
      of infected cells revealed only a slight increase in virus titer with vectors
      carrying the 3pA modification; the titer was increased by 1 with vectors
      containing the extended AT/att, although the viral DNA copy numbers in infected
      cells were similar with both types of vectors. Thus, insufficient integration
      rather than insufficient reverse transcription and/or production of virus RNA is
      the major cause for the low titer obtained with the ProCon vectors. The
      combination of all three modifications resulted in a 2- to 3-log increase in the
      virus titer. These modifications result in expression targeted ProCon vectors
      with titers similar to those of nonmodified MLV-based vectors.

PMID- 14722294
TI  - Replication of poliovirus RNA with complete internal ribosome entry site
      deletions.
AB  - cis-acting RNA sequences and structures in the 5' and 3' nontranslated regions of
      poliovirus RNA interact with host translation machinery and viral replication
      proteins to coordinately regulate the sequential translation and replication of
      poliovirus RNA. The poliovirus internal ribosome entry site (IRES) in the 5'
      nontranslated region (NTR) has been implicated as a cis-active RNA required for
      both viral mRNA translation and viral RNA replication. To evaluate the role of
      the IRES in poliovirus RNA replication, we exploited the advantages of cell-free
      translation-replication reactions and preinitiation RNA replication complexes.
      Genetic complementation with helper mRNAs allowed us to create preinitiation RNA
      replication complexes containing RNA templates with defined deletions in the
      viral open reading frame and the IRES. A series of deletions revealed that no RNA
      elements of either the viral open reading frame or the IRES were required in cis
      for negative-strand RNA synthesis. The IRES was dispensable for both negative-
      and positive-strand RNA syntheses. Intriguingly, although small viral RNAs
      lacking the IRES replicated efficiently, the replication of genome length viral
      RNAs was stimulated by the presence of the IRES. These results suggest that RNA
      replication is not directly dependent on a template RNA first functioning as an
      mRNA. These results further suggest that poliovirus RNA replication is not
      absolutely dependent on any protein-RNA interactions involving the IRES.

PMID- 14722295
TI  - The mature avian leukosis virus subgroup A envelope glycoprotein is metastable,
      and refolding induced by the synergistic effects of receptor binding and low pH
      is coupled to infection.
AB  - The spring-loaded model stipulates that influenza virus infection is coupled to
      the transition of the virus hemagglutinin (HA) from a metastable conformation to
      a highly stable conformation at low pH. The properties of retrovirus envelope
      glycoproteins indicate that infection is coupled to an analogous conformational
      change. As a test of this hypothesis, the requirements for avian leukosis virus A
      (ALV-A) infection were examined. These studies indicate that, like HA, the
      conformation of the mature ALV-A envelope glycoprotein is metastable and that
      infection is linked to refolding at low pH. However, unlike HA, low-pH activation
      is only observed after priming by receptor. Therefore, ALV-A infection is
      dependent on the synergistic effects of receptor binding and low pH, suggesting
      that receptor binding superimposes an additional constraint on activation of ALV
      A fusion that proceeds by a mechanism comparable to that of influenza virus.

PMID- 14722296
TI  - Effects of blocking individual maturation cleavages in murine leukemia virus gag.
AB  - A single protein, termed Gag, is responsible for retrovirus particle assembly.
      After the assembled virion is released from the cell, Gag is cleaved at several
      sites by the viral protease (PR). The cleavages catalyzed by PR bring about a
      wide variety of physical changes in the particle, collectively termed maturation,
      and convert the particle into an infectious virion. In murine leukemia virus
      (MLV) maturation, Gag is cleaved at three sites, resulting in formation of the
      matrix (MA), p12, capsid (CA), and nucleocapsid (NC) proteins. We introduced
      mutations into MLV that inhibited cleavage at individual sites in Gag. All
      mutants had lost the intensely staining ring characteristic of immature
      particles; thus, no single cleavage event is required for this feature of
      maturation. Mutant virions in which MA was not cleaved from p12 were still
      infectious, with a specific infectivity only approximately 10-fold below that of
      the wild type. Particles in which p12 and CA could not be separated from each
      other were noninfectious and lacked a well-delineated core despite the presence
      of dense material in their interiors. In both of these mutants, the dimeric viral
      RNA had undergone the stabilization normally associated with maturation,
      suggesting that this change may depend upon the separation of CA from NC.
      Alteration of the C-terminal end of CA blocked CA-NC cleavage but also reduced
      the efficiency of particle formation and, in some cases, severely disrupted the
      ability of Gag to assemble into regular structures. This observation highlights
      the critical role of this region of Gag in assembly.

PMID- 14722297
TI  - Human immunodeficiency virus type 1-derived lentivirus vectors pseudotyped with
      envelope glycoproteins derived from Ross River virus and Semliki Forest virus.
AB  - Ross River virus (RRV) and Semliki Forest virus (SFV) are two alphaviruses that
      have a high degree of amino acid homology, as well as a very broad host range. We
      show here that envelope glycoproteins derived from both viruses can pseudotype
      human immunodeficiency virus type 1 (HIV-1)-derived lentivirus vectors. Both RRV
      and SFV glycoproteins considerably expand the host range of the lentivirus
      vector, and vectors can be efficiently concentrated by ultracentrifugation. A
      systematic analysis comparing the alphaviral glycoproteins to the vesicular
      stomatitis virus glycoprotein (VSV-G) revealed that lentivirus vectors
      incorporate RRV glycoproteins with an efficiency comparable to that of VSV-G.
      Both pseudotypes have comparable physical titers, but infectious titers with the
      RRV pseudotype are lower than with VSV-G. Incorporation of SFV glycoproteins into
      lentivirus vector is less efficient, leading to decreased physical and infectious
      titers. The transduction rates with VSV-G-, RRV-, and SFV-pseudotyped lentivirus
      vectors into adherent cell lines can be significantly increased by using a
      combination of Polybrene and plates coated with CH-296 recombinant fibronectin
      fragments. Together, our data suggest that RRV and SFV glycoproteins might be
      suitable as alternatives to VSV-G for pseudotyping lentivirus vectors.

PMID- 14722298
TI  - Enterovirus capsid interactions with decay-accelerating factor mediate lytic cell
      infection.
AB  - The cellular receptor usage of numerous human enteroviruses can differ
      significantly between low-cell-culture-passaged clinical isolates and highly
      laboratory-passaged prototype strains. The prototype strain of coxsackievirus A21
      (CVA21) displays a dual-receptor specificity as determined with a receptor
      complex consisting of decay-accelerating factor (DAF) and intercellular adhesion
      molecule 1 (ICAM-1). In this study, the cellular receptor interactions of low
      cell-passage CVA21 clinical isolates with respect to their interactions with cell
      surface-expressed DAF and ICAM-1 were compared to those of the CVA21 prototype
      (Kuykendall) strain. Dual-receptor usage of DAF and ICAM-1 by CVA21 clinical
      isolates was confirmed by cell transfection and radiolabeled binding assays. The
      cellular attachment of clinical and prototype CVA21 strains to cells that
      coexpressed DAF and ICAM-1 was not additive compared to the viral binding to
      cells expressing one or other receptor. In fact, the binding data suggest there
      is an inhibition of CVA21 cellular attachment in environments where high-level
      coexpression of both DAF and ICAM-1 occurs. Antibody cross-linking of DAF
      rendered cells susceptible to lytic infection by the CVA21 clinical isolates. In
      a novel finding, three clinical isolates could, to various degrees, infect and
      lyse DAF-expressing cells in the absence of DAF-antibody cross-linking and ICAM-1
      expression. Sequence analysis of the P1 region of clinical and prototype virus
      genomes identified a number of coding changes that may contribute to the observed
      enhanced DAF usage phenotype of the clinical CVA21 isolates. None of the amino
      acid changes was located in the previously postulated ICAM-1 footprint, a
      receptor-binding environment that was conserved on the capsid surface of all
      CVA21 clinical isolates. Taken together, the data suggest that community
      circulating strains of CVA21 can infect target cells expressing either ICAM-1 or
      DAF alone and that such interactions extend tissue tropism and impact directly on
      viral pathogenesis.

PMID- 14722299
TI  - A novel viral transcript with homology to human interleukin-10 is expressed
      during latent human cytomegalovirus infection.
AB  - Human cytomegalovirus (CMV) establishes latent infections in hematopoietic cells
      such as granulocyte-macrophage progenitors (GM-Ps). During latency the virus is
      sequestered in a nonreplicating state, although limited transcriptional activity
      has been previously reported. In this study we sought to further examine viral
      gene expression during the latent phase of infection. Using an experimental model
      of latency, primary human GM-Ps were latently infected with CMV strain Toledo and
      extracted RNA subjected to reverse transcription-PCR by using CMV gene-specific
      primers. Using this approach, we detected transcription from the UL111.5A region
      of the viral genome. This transcription was also detected in GM-Ps latently
      infected with AD169 and Towne strains, indicating that expression was CMV strain
      independent. Significantly, we detected UL111.5A-region transcripts in
      mononuclear cells from healthy bone marrow and mobilized peripheral blood
      allograft donors, demonstrating expression during natural latent infection.
      Mapping experiments with RNA extracted from latently infected GM-Ps revealed the
      expression of a novel UL111.5A region transcript with a splicing pattern that
      differed from that reported during productive infection of permissive cells. This
      UL111.5A region transcript expressed during latent infection is predicted to
      encode a 139-amino-acid protein with homology to the potent immunosuppressor
      interleukin-10 (IL-10) and to the viral IL-10 homolog that is expressed during
      productive CMV infection. Expression of a latency-associated cmvIL-10 may confer
      upon the virus an ability to avoid immune recognition and clearance during the
      latent phase of infection.

PMID- 14722300
TI  - CD81 is required for hepatitis C virus glycoprotein-mediated viral infection.
AB  - CD81 has been described as a putative receptor for hepatitis C virus (HCV);
      however, its role in HCV cell entry has not been characterized due to the lack of
      an efficient cell culture system. We have examined the role of CD81 in HCV
      glycoprotein-dependent entry by using a recently developed retroviral
      pseudotyping system. Human immunodeficiency virus (HIV) pseudotypes bearing HCV
      E1E2 glycoproteins show a restricted tropism for human liver cell lines. Although
      all of the permissive cell lines express CD81, CD81 expression alone is not
      sufficient to allow viral entry. CD81 is required for HIV-HCV pseudotype
      infection since (i) a monoclonal antibody specific for CD81 inhibited infection
      of susceptible target cells and (ii) silencing of CD81 expression in Huh-7.5
      hepatoma cells by small interfering RNAs inhibited HIV-HCV pseudotype infection.
      Furthermore, expression of CD81 in human liver cells that were previously
      resistant to infection, HepG2 and HH29, conferred permissivity of HCV pseudotype
      infection. The characterization of chimeric CD9/CD81 molecules confirmed that the
      large extracellular loop of CD81 is a determinant for viral entry. These data
      suggest a functional role for CD81 as a coreceptor for HCV glycoprotein-dependent
      viral cell entry.

PMID- 14722301
TI  - Selection of TAR RNA-binding chameleon peptides by using a retroviral replication
      system.
AB  - The interaction between the arginine-rich motif (ARM) of the human
      immunodeficiency virus (HIV) Tat protein and TAR RNA is essential for Tat
      activation and viral replication. Two related lentiviruses, bovine
      immunodeficiency virus (BIV) and Jembrana disease virus (JDV), also require Tat
      ARM-TAR interactions to mediate activation, but the viruses have evolved
      different RNA-binding strategies. Interestingly, the JDV ARM can act as a
      "chameleon," adopting both the HIV and BIV TAR binding modes. To examine how RNA
      protein interactions may evolve in a viral context and possibly to identify
      peptides that recognize HIV TAR in novel ways, we devised a retroviral system
      based on HIV replication to amplify and select for RNA binders. We constructed a
      combinatorial peptide library based on the BIV Tat ARM and identified peptides
      that, like the JDV Tat ARM, also function through HIV TAR, revealing unexpected
      sequence characteristics of an RNA-binding chameleon. The results suggest that a
      retroviral screening approach may help identify high-affinity TAR binders and may
      provide new insights into the evolution of RNA-protein interactions.

PMID- 14722302
TI  - Dysregulation of the polo-like kinase pathway in CD4+ T cells is characteristic
      of pathogenic simian immunodeficiency virus infection.
AB  - CD4(+) T-cell dysfunction highlighted by defects within the intracellular
      signaling cascade and cell cycle has long been characterized as a direct and/or
      indirect consequence of human immunodeficiency virus (HIV) infection in humans
      and simian immunodeficiency virus (SIV) infection in rhesus macaques (RM).
      Dysregulation of the M phase of the cell cycle is a well-documented effect of HIV
      or SIV infection both in vivo and in vitro. In this study the effect of SIV
      infection on the modulation of two important regulators of the M phase-polo-like
      kinases Plk3 and Plk1-was investigated. We have previously shown that Plk3 is
      markedly downregulated in CD4(+) T cells from SIV-infected disease-susceptible RM
      but not SIV-infected disease-resistant sooty mangabeys (SM), denoting an
      association of downregulation with disease progression. Here we show that, in
      addition to the downregulation, Plk3 exhibits aberrant activation patterns in the
      CD4(+) T cells from SIV-infected RM following T-cell receptor stimulation.
      Interestingly, in vitro SIV infection of CD4(+) T cells leads to the
      upregulation, rather than downregulation, of Plk3, suggesting that different
      mechanisms operate in vitro and in vivo. In addition, CD4(+) T cells from RM with
      high viral loads exhibited consistent and significant upregulation of Plk1,
      concurrent with an aberrant activation-induced Plk1 response, suggesting complex
      mechanisms of SIV-induced M-phase abnormalities in vivo. Altogether this study
      presents a novel mechanism underlying M-phase defects observed in CD4(+) T cells
      from HIV or SIV-infected disease-susceptible humans and RM which may contribute
      to aberrant T-cell responses and disease pathogenesis.

PMID- 14722303
TI  - Systemic immune deficiency necessary for cytomegalovirus invasion of the mature
      brain.
AB  - Cytomegalovirus (CMV) is a significant opportunistic pathogen associated with
      AIDS and immunosuppressive therapy. Infection of the mature central nervous
      system (CNS) can cause significant pathology with associated neurological
      deficits, mental disorders, and cognitive impairment and may have potentially
      fatal consequences. Using genetically immunocompromised mice, we studied
      mechanisms of CMV invasion into, and behavior within, the CNS. Adult
      immunodeficient (nude and SCID) and control mice were peripherally infected with
      recombinant mouse CMV expressing a green fluorescent protein reporter gene.
      Control mice actively eliminated acute peripheral infection and were resistant to
      invasion of CMV into the brain. In contrast, virus infected brains of
      immunodeficient mice but only after a minimum of 21 days postinoculation. After
      inoculation, CMV was found in circulating leukocytes (MAC-3/CD45(+)) and in
      leukocytes within the brain, suggesting these cells as a possible source of CMV
      entry into the CNS. CNS infection was observed in many different cell types,
      including neurons, glial cells, meninges, ependymal cells, and cells of cerebral
      vessels. Infection foci progressively expanded locally to adjacent cells,
      resulting in meningitis, choroiditis, encephalitis, vasculitis, and necrosis;
      clear indication of axonal transport of CMV was not found. Regional distribution
      of CMV was unique in each brain, consisting of randomly distributed, unilateral
      foci. Testing whether CMV gained access to brain through nonspecific vascular
      disruption, vascular injections of a tracer molecule revealed no obvious
      disruption of the blood brain barrier in mice with CMV in the brain. Results
      indicate the importance of host adaptive immunity (particularly T cells) in
      controlling entry and dissemination of CMV into the brain and are consistent with
      the view that virus may be carried into the brain by circulating mononuclear
      cells that traffic through the blood brain barrier.

PMID- 14722304
TI  - An acidic cluster of human cytomegalovirus UL99 tegument protein is required for
      trafficking and function.
AB  - The human cytomegalovirus (HCMV) virion is comprised of a linear double-stranded
      DNA genome, proteinaceous capsid and tegument, and a lipid envelope containing
      virus-encoded glycoproteins. Of these components, the tegument is the least well
      defined in terms of both protein content and function. Several of the major
      tegument proteins are phosphoproteins (pp), including pp150, pp71, pp65, and
      pp28. pp28, encoded by the UL99 open reading frame (ORF), traffics to vacuole
      like cytoplasmic structures and was shown recently to be essential for
      envelopment. To elucidate the UL99 amino acid sequences necessary for its
      trafficking and function in the HCMV replication cycle, two types of viral
      mutants were analyzed. Using a series of recombinant viruses expressing various
      UL99-green fluorescent protein fusions, we demonstrate that myristoylation at
      glycine 2 and an acidic cluster (AC; amino acids 44 to 57) are required for the
      punctate perinuclear and cytoplasmic (vacuole-like) localization observed for
      wild-type pp28. A second approach involving the generation of several UL99
      deletion mutants indicated that at least the C-terminal two-thirds of this ORF is
      nonessential for viral growth. Furthermore, the data suggest that an N-terminal
      region of UL99 containing the AC is required for viral growth. Regarding virion
      incorporation or UL99-encoded proteins, we provide evidence that suggests that a
      hypophosphorylated form of pp28 is incorporated, myristoylation is required, and
      sequences within the first 57 amino acids are sufficient.

PMID- 14722305
TI  - Both the PPPY and PTAP motifs are involved in human T-cell leukemia virus type 1
      particle release.
AB  - In retroviruses, the late (L) domain has been defined as a conserved motif in the
      Gag polyprotein precursor that, when mutated, leads to the emergence of virus
      particles that fail to pinch off from the plasma membrane. These domains have
      been observed to contain the PPXY, PTAP, or YXXL motifs. The deltaretroviruses,
      which include bovine leukemia virus (BLV) and human T-cell leukemia virus type 1
      (HTLV-1) and HTLV-2, have a conserved PPPY motif in the C-terminal region of the
      matrix (MA) domain of Gag, while HTLV-1 also encodes a PTAP motif in MA. In this
      study, we analyzed the roles of the PPPY and PTAP motifs in the C terminus of MA
      in HTLV-1 particle release. Mutation of either motif (i.e., PPPY changed to APPY
      or PTAP changed to PTRP) reduced budding efficiencies. Particle buds and electron
      dense regions of plasma membrane were observed by electron microscopy. When the
      locations of PPPY and PTAP were switched, particle release was eliminated.
      Intriguingly, the replacement of the PTAP motif with either the PPPY or YPDL
      motifs did not influence the release of virus particles, but the replacement of
      the PPPY motif with either PTAP or YPDL eliminated particle production. This
      indicates that the role that PPPY plays in HTLV-1 budding cannot be replaced with
      either PTAP or YPDL. A similar observation was made with the BLV PPPY motif.
      Finally, HTLV-1 particle release was found to be sensitive to proteasome
      inhibitors, implicating a role for ubiquitin in HTLV-1 budding. In summary, our
      observations indicate that (i) the PPPY motif plays a crucial role in virus
      budding and (ii) the PTAP motif plays a more subtle role in HTLV-1 particle
      release. Each of these motifs may play an important role in virus release from
      specific cell types and therefore be important in efficient virus spread and
      transmission.

PMID- 14722306
TI  - Virus-host cell interactions during hepatitis C virus RNA replication: impact of
      polyprotein expression on the cellular transcriptome and cell cycle association
      with viral RNA synthesis.
AB  - Considerable controversy surrounds the impact of hepatitis C virus (HCV) protein
      expression on viability of host cells and regulation of the cell cycle. Both
      promotion of cellular proliferation and apoptosis have been observed in different
      experimental systems. To determine whether expression of the entire complement of
      HCV proteins in the context of ongoing viral RNA replication significantly alters
      the host cell transcriptome and cell cycle regulatory processes, we carried out
      high-density oligonucleotide microarray studies and analyzed cell cycle
      distributions and S-phase entry in Huh7 cell clones harboring selectable, full
      length, replicating HCV RNAs that express the entire genotype 1b, HCV-N
      polyprotein, and clonally related cells in which all viral RNA was eliminated by
      prior treatment with alpha interferon. Oligonucleotide microarray analyses
      revealed only subtle, coordinated differences in the mRNA profiles of cells
      containing replicating viral RNA and their interferon-cured progeny, with
      variation between different cell clones having a greater influence on the
      cellular transcriptome than the presence or absence of replicating HCV RNA. Flow
      cytometric analysis demonstrated no significant differences in cell cycle
      distribution among populations of asynchronously growing cells of both types.
      Cell lines containing replicating viral RNA and their interferon-cured progeny
      were able to reenter the cell cycle similarly after transient G(1) arrest. In
      contrast, although viral protein expression and genome replication did not alter
      cell cycle control in these cells, HCV genome replication was highly dependent on
      cellular proliferation, with viral RNA synthesis strongly decreased in poorly
      proliferating, confluent, or serum-starved cells and substantially enhanced in
      the S phase of the cell cycle.

PMID- 14722307
TI  - Removal of N-linked glycosylation sites in the V1 region of simian
      immunodeficiency virus gp120 results in redirection of B-cell responses to V3.
AB  - One mechanism of immune evasion utilized by human immunodeficiency virus (HIV)
      and simian immunodeficiency virus (SIV) envelope glycoproteins is the presence of
      a dense carbohydrate shield. Accumulating evidence from in vitro and in vivo
      experiments suggests that alterations in N-linked glycosylation of SIV gp120 can
      enhance host humoral immune responses that may be involved in immune control. The
      present study was designed to determine the ability of glycosylation mutant
      viruses to redirect antibody responses to shielded envelope epitopes. The
      influence of glycosylation on the maturation and specificity of antibody
      responses elicited by glycosylation mutant viruses containing mutations of
      specific N-linked sites in and near the V1 and V2 regions of SIVmac239 gp120 was
      determined. Results from these studies demonstrated a remarkably similar
      maturation of antibody responses to native, fully glycosylated envelope proteins.
      However, analyses of antibodies to defined envelope domains revealed that
      mutation of glycosylation sites in V1 resulted in increased antibody recognition
      to epitopes in V1. In addition, we demonstrated for the first time that mutation
      of glycosylation sites in V1 resulted in a redirection of antibody responses to
      the V3 loop. Taken together, these results demonstrate that N-linked
      glycosylation is a determinant of SIV envelope B-cell immunogenicity in addition
      to in vitro antigenicity. In addition, our results demonstrate that the absence
      of N-linked carbohydrates at specific sites can influence the exposure of
      epitopes quite distant in the linear sequence.

PMID- 14722308
TI  - Effects of mutations in the cytoplasmic domain of herpes simplex virus type 1
      glycoprotein B on intracellular transport and infectivity.
AB  - Herpes simplex virus type 1 (HSV-1) is a human pathogen of the alphaherpesvirus
      family which infects and spreads in the nervous system. Glycoproteins play a key
      role in the process of assembly and maturation of herpesviruses, which is
      essential for neuroinvasion and transneuronal spread. Glycoprotein B (gB) is a
      main component of the HSV-1 envelope and is necessary for the production of
      infectious particles. The cytoplasmic domain of gB, the longest one among HSV-1
      glycoproteins, contains several highly conserved peptide sequences homologous to
      motifs involved in intracellular sorting. To determine the specific roles of
      these motifs in processing, subcellular localization, and the capacity of HSV-1
      gB to complement a gB-null virus, we generated truncated or point mutated forms
      of a green fluorescent protein (GFP)-tagged gB. GFP-gB with a deletion in the
      acidic cluster DGDADEDDL (amino acids [aa] 896 to 904) behaved the same as the
      parental form. Deletion or disruption of the YTQV motif (aa 889 to 892) abolished
      internalization and reduced complementation by 60%. Disruption of the LL motif
      (aa 871 to 872) impaired the return of the protein to the trans-Golgi network
      (TGN) while enhancing its recycling to the plasma membrane. Truncations from
      residue E 857 abolished transport and processing of the truncated proteins, which
      had null complementation activity, through the Golgi complex. Altogether, our
      results favor a model in which HSV-1 gets its final envelope in the TGN, and they
      suggest that endocytosis, albeit not necessary, might play a role in infectivity.

PMID- 14722309
TI  - Cell-type-dependent targeting of human immunodeficiency virus type 1 assembly to
      the plasma membrane and the multivesicular body.
AB  - The human immunodeficiency virus type 1 (HIV-1) assembly-and-release pathway
      begins with the targeting of the Gag precursor to the site of virus assembly. The
      molecular mechanism by which Gag is targeted to the appropriate subcellular
      location remains poorly understood. Based on the analysis of mutant Gag proteins,
      we and others have previously demonstrated that a highly basic patch in the
      matrix (MA) domain of Gag is a major determinant of Gag transport to the plasma
      membrane. In this study, we determined that in HeLa and T cells, the MA mutant
      Gag proteins that are defective in plasma membrane targeting form virus particles
      in a CD63-positive compartment, defined as the late endosome or multivesicular
      body (MVB). Interestingly, we find that in primary human macrophages, both wild
      type (WT) and MA mutant Gag proteins are targeted specifically to the MVB.
      Despite the fact that particle assembly in macrophages occurs at an intracellular
      site rather than at the plasma membrane, we observe that WT Gag expressed in this
      cell type is released as extracellular virions with high efficiency. These
      results demonstrate that Gag targeting to and assembly in the MVB are
      physiologically important steps in HIV-1 virus particle production in macrophages
      and that particle release in this cell type may follow an exosomal pathway. To
      determine whether Gag targeting to the MVB is the result of an interaction
      between the late domain in p6(Gag) and the MVB sorting machinery (e.g., TSG101),
      we examined the targeting and assembly of Gag mutants lacking p6. Significantly,
      the MVB localization of Gag was still observed in the absence of p6, suggesting
      that an interaction between Gag and TSG101 is not required for Gag targeting to
      the MVB. These data are consistent with a model for Gag targeting that postulates
      two different cellular binding partners for Gag, one on the plasma membrane and
      the other in the MVB.

PMID- 14722310
TI  - Astrovirus-induced synthesis of nitric oxide contributes to virus control during
      infection.
AB  - Astrovirus is one of the major causes of infant and childhood diarrhea worldwide.
      Our understanding of astrovirus pathogenesis trails behind our knowledge of its
      molecular and epidemiologic properties. Using a recently developed small-animal
      model, we investigated the mechanisms by which astrovirus induces diarrhea and
      the role of both the adaptive and innate immune responses to turkey astrovirus
      type-2 (TAstV-2) infection. Astrovirus-infected animals were analyzed for changes
      in total lymphocyte populations, alterations in CD4(+)/CD8(+) ratios, production
      of virus-specific antibodies (Abs), and macrophage activation. There were no
      changes in the numbers of circulating or splenic lymphocytes or in CD4(+)/CD8(+)
      ratios compared to controls. Additionally, there was only a modest production of
      virus-specific Abs. However, adherent spleen cells from infected animals produced
      more nitric oxide (NO) in response to ex vivo stimulation with
      lipopolysaccharide. In vitro analysis demonstrated that TAstV-2 induced
      macrophage production of inducible nitric oxide synthase. Studies using NO donors
      and inhibitors in vivo demonstrated, for the first time, that NO inhibited
      astrovirus replication. These studies suggest that NO is important in limiting
      astrovirus replication and are the first, to our knowledge, to describe the
      potential role of innate immunity in astrovirus infection.

PMID- 14722311
TI  - Cross-genotype immunity to hepatitis C virus.
AB  - Recent studies in humans and chimpanzees suggest that immunity can be induced to
      diminish the incidence of chronic hepatitis C virus (HCV) infection. However, the
      immunity that promotes viral recovery is poorly understood, and whether the
      breadth of this adaptive immunity is sufficient to overcome the substantial
      intergenotype antigenic diversity represents a final obstacle to demonstrating
      the feasibility of vaccine development. Here we demonstrate that recovery from a
      genotype 1 HCV infection protects chimpanzees against infection with
      representatives of other genotypes that exhibit up to 30% divergence at the amino
      acid level, including challenges with genotype 4, a mixture of genotypes 2 and 3,
      and a complex inoculum containing genotypes 1, 2, 3, and 4. In each instance, the
      level and duration of viremia were markedly reduced in comparison to the primary
      infection in the same animal. The data indicate that epitopes conserved between
      genotypes must play an essential role in immunity. The inocula used in the
      rechallenge studies induced typical primary infection profiles in naive
      chimpanzees. Rechallenge infections were associated with rapid increases in the
      intrahepatic transcripts of interferon-stimulated genes, even in animals
      exhibiting apparent sterilizing immunity. Protective immunity was often
      associated with an early increase in gamma interferon transcripts in the liver
      and increases in intrahepatic transcripts of Mig, a T-cell chemokine that is a
      gamma interferon response gene. These studies are the first to show that cross
      genotype immunity can be induced to HCV, demonstrating the feasibility of
      developing a vaccine protective against all HCV strains.

PMID- 14722312
TI  - Influence of the route of infection on development of T-cell receptor beta-chain
      repertoires of reovirus-specific cytotoxic T lymphocytes.
AB  - It is well established that the route of infection affects the nature of the
      adaptive immune response. However, little is known about the effects of the route
      of exposure on development of cytotoxic T-lymphocyte (CTL) responses. Alternative
      antigen-presenting cell populations, tissue-restricted expression of class I
      major histocompatibility complex-encoded molecules, and unique T-cell receptor
      (TCR)-bearing cells in mucosal tissues could influence the selection and
      expansion of responder T cells. This study addresses the question of whether the
      route of virus infection affects the selection and expansion of subpopulations of
      virus-specific CTLs. Mice were infected orally or in the hind footpads with
      reovirus, and the repertoires of TCR beta-chains expressed on virus-specific
      CD8(+) T cells in Peyer's patches or lymph nodes and spleens were examined.
      CD8(+) cells expressing the variable gene segment of the TCR beta-chain 6
      (Vbeta6) expanded in the spleens of mice infected by either route and in CTL
      lines established from the spleens and draining lymphoid tissues. Adoptively
      transferred Vbeta6(+) CD8(+) T cells from orally or parenterally infected donors
      expanded in reovirus-infected severe combined immunodeficient recipient mice and
      mediated cytotoxicity ex vivo. Furthermore, recovered Vbeta6(+) cells were
      enriched for clones utilizing uniform complementarity-determining region 3 (CDR3)
      lengths. However, sequencing of CDR3beta regions from Vbeta6(+) CD8(+) cells
      indicated that Jbeta gene segment usage is significantly more restricted in CTLs
      from orally infected mice, suggesting that the route of infection affects
      selection and/or subsequent expansion of virus-specific CTLs.

PMID- 14722313
TI  - The movement protein of cowpea mosaic virus binds GTP and single-stranded nucleic
      acid in vitro.
AB  - The movement protein (MP) of Cowpea mosaic virus forms tubules in plasmodesmata
      to enable the transport of mature virions. Here it is shown that the MP is
      capable of specifically binding riboguanosine triphosphate and that mutational
      analysis suggests that GTP binding plays a role in the targeted transport of the
      MP. Furthermore, the MP is capable of binding both single-stranded RNA and single
      stranded DNA in a non-sequence-specific manner, and the GTP- and RNA-binding
      sites do not overlap.

PMID- 14722314
TI  - Ability of wild-type and mutant lysyl-tRNA synthetase to facilitate tRNA(Lys)
      incorporation into human immunodeficiency virus type 1.
AB  - The major human tRNA(Lys) isoacceptors, tRNA1,2Lys and tRNA3Lys, are selectively
      packaged into human immunodeficiency virus type 1 (HIV-1) during assembly, where
      tRNA3Lys acts as a primer for reverse transcription. Lysyl-tRNA synthetase
      (LysRS) is also incorporated into HIV-1, independently of tRNA(Lys), via its
      interaction with Gag, and it is a strong candidate for being the signal that
      specifically targets tRNA(Lys) for viral incorporation. Expression of exogenous
      wild-type LysRS in cells results in an approximately twofold increase in the
      viral packaging of both LysRS and tRNA(Lys). Herein, we show that this increase
      in tRNA(Lys) incorporation into virions is dependent upon the ability of LysRS to
      bind to tRNA(Lys) but not upon its ability to aminoacylate the tRNA(Lys). COS7
      cells were cotransfected with plasmids coding for both HIV-1 and either wild-type
      or mutant human LysRS, all of which are incorporated into virions with similar
      efficiency. However, N-terminally truncated LysRS, which binds poorly to
      tRNA(Lys), does not increase tRNA(Lys) packaging into viruses, while C-terminally
      truncated LysRS, which binds to but does not aminoacylate tRNA(Lys), still
      facilitates an increase in tRNA(Lys) packaging into virions.

PMID- 14722315
TI  - Severe acute respiratory syndrome coronavirus sequence characteristics and
      evolutionary rate estimate from maximum likelihood analysis.

PMID- 14722316
TI  - Stimulation of serotonin2C receptors blocks the hyperactivation of midbrain
      dopamine neurons induced by nicotine administration.
AB  - In vivo electrophysiological techniques were used to study the effect of nicotine
      on the basal activity of dopamine (DA)-containing neurons in the substantia nigra
      pars compacta (SNc) and the ventral tegmental area (VTA) of chloral hydrate
      anesthetized rats. Acute i.v. injections of nicotine (25-400 microg/kg) caused a
      dose-dependent increase of the firing rate and the bursting activity of DA
      neurons both in the SNc and the VTA. Repeated daily injection of nicotine (1
      mg/kg i.p.) for 10 consecutive days did not cause any significant change in the
      basal activity of DA neurons in the SNc and the VTA. Acute challenge with
      nicotine (25-400 microg/kg i.v.) in animals treated repeatedly with this drug
      caused a dose-related excitation of DA neurons in both areas. To test the
      hypothesis that stimulation of 5-hydroxytryptamine (5-HT, serotonin)(2C)
      receptors could affect nicotine-induced stimulation of DA neuronal activity, the
      selective 5-HT(2C) receptor agonist RO 60-0175 was used. Pretreatment with 100
      microg/kg i.v. (S)-2-(chloro-5-fluoro-indo-l-yl)-l-methylethylamine 1:1
      C(4)H(4)O(4) (RO 60-0175) prevented the enhancement in DA neuronal firing rate
      elicited by acute nicotine (25-400 microg/kg i.v.) in the SNc of both drug naive
      and chronically treated rats but was devoid of any significant effect in the VTA.
      Moreover, the dose of 300 microg/kg i.v. RO 60-0175 significantly reduced the
      stimulatory effect of VTA DA neurons induced by acute challenge with nicotine (25
      400 microg/kg i.v.) both in drug naive and chronically treated rats. It is
      concluded that selective activation of 5-HT(2C) receptors can block the
      stimulatory action of nicotine on midbrain DA neuronal activity.

PMID- 14722317
TI  - Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the
      multidrug resistance proteins MRP1, MRP2, and MRP3.
AB  - Ethinylestradiol (EE) is one of the key constituents of oral contraceptives.
      Major metabolites of EE in humans are the glucuronide and sulfate conjugates, EE
      3-O-glucuronide (EE-G) and EE-3-O-sulfate (EE-S). In the present study, transport
      of EE-G and EE-S by the human multidrug resistance proteins MRP1, MRP2, and MRP3
      was investigated using inside-out membrane vesicles, isolated from Sf9 cells
      expressing human MRP1, MRP2, or MRP3. Vesicular uptake studies showed that EE-G
      was not a substrate for MRP1, whereas an ATP-dependent and saturable transport of
      [(3)H]EE-G was observed in MRP2 (K(m) of 35.1 +/- 3.5 microM) and MRP3 (K(m) of
      9.2 +/- 2.3 microM) containing vesicles. EE-S was not transported by either MRP1,
      MRP2, or MRP3. However, low concentrations of EE-S stimulated MRP2-mediated
      uptake of ethacrynic acid glutathione. EE-S also stimulated MRP2 and MRP3
      mediated uptake of 17beta-estradiol-17beta-D-glucuronide. Interestingly, EE-S
      stimulated strongly MRP2- and MRP3-mediated uptake of EE-G by increasing its
      apparent transport affinity, whereas no reciprocal stimulation of EE-S uptake by
      EE-G was observed. These data indicate that EE-S allosterically stimulates MRP2-
      and MRP3-mediated transport of EE-G and is not cotransported with EE-G. Our
      studies demonstrate specific active transport of a pharmacologically relevant
      drug conjugate by human MRP2 and MRP3, involving complex interactions with other
      organic anions. We also suggest that caution needs to be taken when using only
      competition studies as screening tools to identify substrates or inhibitors of
      MRP-mediated transport.

PMID- 14722318
TI  - AT2 receptors attenuate AT1 receptor-induced phospholipase D activation in
      vascular smooth muscle cells.
AB  - Previous studies indicate that angiotensin (AT)(1) receptor-induced activation of
      phospholipase D (PLD) may importantly contribute to vascular hypertrophy, injury,
      and contraction. However, the role of AT(2) receptors in regulating AT(1)
      receptor-induced PLD activation is unknown. In this study, we identified
      angiotensin II receptors on cultured preglomerular vascular smooth muscle cells
      (PGSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY)
      by reverse transcription-polymerase chain reaction (RT-PCR) and binding assays
      and examined their functional effects on angiotensin II-mediated PLD activity.
      Both RT-PCR and binding indicated that cultured SHR and WKY PGSMCs expressed
      AT(1) and AT(2) receptors, and the combined total of AT(1) and AT(2) receptors
      was similar between the strains. However, the number of AT(1) and AT(2) receptors
      differed between SHR and WKY PGSMCs in so much as the ratio of AT(1) to AT(2)
      receptors was approximately 1 to 1 and 3 to 1 in WKY and SHR PGSMCs,
      respectively. As previously reported, angiotensin II more potently activated PLD
      in SHR PGSMCs (SHR EC(50) = 4 nM; WKY EC(50) = 47 nM). Addition of an AT(2)
      receptor-specific antagonist or agonist shifted the angiotensin II-mediated PLD
      concentration-response curve of WKY PGSMCs in a manner consistent with AT(2)
      receptors producing an inhibitory signal. In contrast, in SHR little change was
      observed. Our findings indicate that the ratio of AT(1) to AT(2) receptors in
      vascular smooth muscle cells may be a determinant of the net effects of
      angiotensin II on PLD activity due to AT(2)-dependent inhibition of AT(1)
      mediated PLD activity. Furthermore, cultured WKY PGSMCs provide an excellent
      model system to study endogenous AT(2) receptor signal transduction.

PMID- 14722319
TI  - Quantitative evaluation of the drug-drug interactions between methotrexate and
      nonsteroidal anti-inflammatory drugs in the renal uptake process based on the
      contribution of organic anion transporters and reduced folate carrier.
AB  - The present study examined the possible role of transporters in the drug-drug
      interactions between methotrexate (MTX) and nonsteroidal anti-inflammatory drugs
      (NSAIDs) in the renal uptake process of MTX. MTX is recognized by reduced folate
      carrier (RFC-1) and rat organic anion transporters (rOat1 and rOat3) as a
      substrate. Uptake of MTX by kidney slices was saturable and inhibited potently by
      dibromosulfophthalein. Folate and benzylpenicillin (PCG) inhibited the uptake by
      30 to 40% and 40 to 50% of the total saturable uptake of MTX by kidney slices,
      respectively, whereas the effect of p-aminohippurate (PAH) was minimal at the
      concentration selective for rOat1. In contrast, the uptake of 5
      methyltetrahydrofolate by the kidney slices was inhibited by MTX, folate, and
      dibromosulfophthalein, but not by PAH and PCG. These results suggest that rOat3
      and RFC-1 are almost equally involved in the uptake of MTX by the kidney slices,
      whereas RFC-1 is responsible for the renal uptake of 5-methyltetrahydrofolate.
      NSAIDs, except salicylate, were potent inhibitors of rOat3 (K(i) of 1.3-19
      microM), but weak inhibitors of RFC-1 (K(i) of 70-310 microM). This is in a good
      agreement with the biphasic inhibition profiles of NSAIDs for the uptake of MTX
      by kidney slices. These results suggest that the renal uptake of MTX is not so
      greatly affected by NSAIDs as expected from the inhibition of rOat3-mediated
      transport.

PMID- 14722320
TI  - Pharmacological characterization and cross talk of alpha1a- and alpha1b
      adrenoceptors coexpressed in human embryonic kidney 293 cells.
AB  - We established three human embryonic kidney (HEK) 293 cell lines stably
      expressing alpha(1)-adrenoceptor (AR) subtypes, one (alpha(1A), (1B)-AR)
      coexpressing both receptors and the other two (alpha(1A)-AR and alpha(1B)-AR)
      expressing each receptor in isolation. In the alpha(1A), (1B)-AR cells, both
      receptors were clearly distinguished by the alpha(1A)-selective ligands (-)-1(3
      hydroxypropyl)-5-((2R)-2-([2-(2,2,2
      trifluoroethyl]oxy]phenyl)oxy)ethyl]amino)propyl)-2,3-dihydro-1H-indole-7
      carboxamide (KMD-3213) and methoxamine, but not by the subtype-nonselective
      ligands prazosin and phenylephrine. In all three cell lines, phenylephrine caused
      a concentration-dependent increase in inositol phosphates and an increase in
      extracellular signal-regulated kinase 1/2 (ERK1/2) activation. However, there was
      a 2-fold or greater maximal response to phenylephrine and a somewhat higher
      agonist potency in ERK1/2 activation in the alpha(1A,1B)-AR cells, compared with
      the responses of cells expressing either receptor individually (alpha(1A)-AR or
      alpha(1B)-AR). Furthermore, the antagonistic affinities of prazosin (pK(b) of
      10.1) and KMD-3213 (9.4) for inhibiting the phenylephrine response were
      intermediate between the values for inhibition in alpha(1A)-AR cells (prazosin,
      9.3; KMD-3213, 10.5) and alpha(1B)-AR cells (prazosin, 11.0; KMD-3213, 8.1). The
      inhibitor pK(b) values in alpha(1A), (1B)-AR also differed from their ligand
      binding affinities measured in alpha(1A)-AR and alpha(1B)-AR cells. In contrast,
      the alpha(1A)-selective agonist methoxamine, which did not activate alpha(1B)-AR
      cells, stimulated either alpha(1A,) (1B)-AR or alpha(1A)-AR cells with a
      comparable potency and maximum effectiveness. Our data indicate that when
      coexpressed in the same cell, the activation of common pathways by individual AR
      receptor subtypes by a nonselective agonist can exhibit enhanced responsiveness
      and a distinct antagonist affinity compared with the parameters for the same
      receptors, when expressed alone in the same cell background.

PMID- 14722321
TI  - A potent and selective histamine H4 receptor antagonist with anti-inflammatory
      properties.
AB  - Histamine mediates its physiological function through binding to four known
      histamine receptors. Here, we describe the first selective antagonist of the
      histamine H4 receptor, the newest member of the histamine receptor family, and
      provide evidence that such antagonists have anti-inflammatory activity in vivo. 1
      [(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine (JNJ 7777120) has a K(i) of
      4.5 nM versus the human receptor and a pA(2) of 8.1. It is equipotent against the
      human, mouse, and rat receptors. It exhibits at least 1000-fold selectivity over
      H1, H2, or H3 receptors and has no cross-reactivity against 50 other targets.
      This compound has an oral bioavailability of approximately 30% in rats and 100%
      in dogs, with a half-life of approximately 3 h in both species. JNJ 7777120
      blocks histamine-induced chemotaxis and calcium influx in mouse bone marrow
      derived mast cells. In addition, it can block the histamine-induced migration of
      tracheal mast cells from the connective tissue toward the epithelium in mice. JNJ
      7777120 significantly blocks neutrophil infiltration in a mouse zymosan-induced
      peritonitis model. This model is reported to be mast cell-dependent, which
      suggests that the compound effect may be mediated by mast cells. These results
      indicate that the histamine H4 receptor plays a role in the inflammatory process.
      Selective H4 receptor antagonists like JNJ 7777120 may have the potential to be
      useful in treating inflammation in humans.

PMID- 14722322
TI  - Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell
      line.
AB  - Induction of drug-metabolizing enzymes and transporters can cause drug-drug
      interactions and loss of efficacy. In vitro induction studies traditionally use
      primary hepatocyte cultures and enzyme activity with selected marker compounds.
      We investigated the use of a novel human hepatocyte clone, the Fa2N-4 cell line,
      as an alternative reagent, which is readily available and provides a consistent,
      reproducible system. We used the Invader assay to monitor gene expression in
      these cells. This assay is a robust, yet simple, high-throughput system for
      quantification of mRNA transcripts. CYP1A2, CYP3A4, CYP2C9, UGT1A, and MDR1
      transcripts were quantified from total RNA extracts from Fa2N-4 cells treated
      with a panel of known inducers and compared with vehicle controls. In addition,
      we used enzyme activity assays to monitor the induction of CYP1A2, CYP2C9, and
      CYP3A4. The Fa2N-4 cells responded in a similar manner as primary human
      hepatocytes. Treatment with 10 microM rifampin resulted in increases in CYP3A4
      mRNA (17-fold) and activity (6-beta-hydroxytestoterone formation, 9-fold); and in
      CYP2C9 mRNA (4-fold) and activity (4'-hydroxydiclofenac formation, 2-fold).
      Treatment with 50 microM beta-naphthoflavone resulted in increases in CYP1A2 mRNA
      (15-fold) and activity (7-ethoxyresorufin O-dealkylation, 27-fold). UGT1A mRNA
      was induced by beta-naphthoflavone (2-fold), and MDR1 (P-glycoprotein) mRNA was
      induced by rifampin (3-fold). These preliminary data using a few prototypical
      inducers show that Fa2N-4 cells can be a reliable surrogate for primary human
      hepatocytes, and, when used in conjunction with the Invader technology, could
      provide a reliable assay for assessment of induction of drug-metabolizing enzymes
      and transporters.

PMID- 14722323
TI  - The neuroprotective effect of 2-(3-pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698),
      a novel alpha7 ligand, is prevented through angiotensin II activation of a
      tyrosine phosphatase.
AB  - We have recently provided evidence for nicotine-induced complex formation between
      the alpha7 nicotinic acetylcholine receptor (nAChR) and the tyrosine
      phosphorylated enzyme Janus kinase 2 (JAK2) that results in subsequent activation
      of phosphatidylinositol-3-kinase (PI-3-K) and Akt. Nicotine interaction with the
      alpha7 nAChR inhibits Abeta (1-42) interaction with the same receptor, and the
      Abeta (1-42)-induced apoptosis is prevented through nicotine-induced activation
      of JAK2. These effects can be shown by measuring markers of cytotoxicity,
      including the cleavage of the nuclear protein poly(ADP-ribose) polymerase (PARP),
      the induction of caspase 3, or cell viability. In this study, we found that 2-(3
      pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698), a novel alpha7-selective agonist,
      exerts neuroprotective effects via activation of the JAK2/PI-3K cascade, which
      can be neutralized through activation of the angiotensin II (Ang II) AT(2)
      receptor. Vanadate not only augmented the TC-1698-induced tyrosine
      phosphorylation of JAK2 but also blocked the Ang II neutralization of TC-1698
      induced neuroprotection against Abeta (1-42)-induced cleavage of PARP.
      Furthermore, when SHP-1 was neutralized via antisense transfection, the Ang II
      inhibition of TC-1698-induced neuroprotection against Abeta (1-42) was prevented.
      These results support the main hypothesis that states that JAK2 plays a central
      role in the nicotinic alpha7 receptor-induced activation of the JAK2-PI-3K
      cascade in PC12 cells, which ultimately contribute to nAChR-mediated
      neuroprotection. Ang II inhibits this pathway through the AT(2) receptor
      activation of the protein tyrosine phosphatase SHP-1. This study supports central
      and opposite roles for JAK2 and SHP-1 in the control of apoptosis and alpha7
      mediated neuroprotection in PC12 cells.

PMID- 14722324
TI  - Receptor/gene-mediated pharmacodynamic effects of methylprednisolone on
      phosphoenolpyruvate carboxykinase regulation in rat liver.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme for
      gluconeogenesis. To investigate underlying mechanisms of corticosteroid (CS)
      action in regulating glucose, temporal patterns of hepatic PEPCK gene expression,
      enzyme activity, and cAMP content were examined in adrenalectomized rats
      receiving acute and chronic methylprednisolone (MPL) treatments. After single MPL
      intravenous doses, PEPCK mRNA showed a fast increase, reaching a maximum at
      around 0.75 h, which was followed by an immediate decline to below baseline after
      4 h, an apparent acute tolerance/rebound phenomenon. However, PEPCK enzyme showed
      continuous hyperactivity for over 72 h. This may be the result of generation of
      cAMP, an important inducer of PEPCK activity, which peaked at around 6 h. During
      7-day subcutaneous infusion of MPL, PEPCK mRNA showed profiles consistent with
      single-dose results, whereas PEPCK activity increased to a comparable maximum
      followed by a slow decline. However, the extent of cAMP induction was markedly
      higher during infusion, which could be attributed to amplification of cAMP
      synthesis and/or a stabilizing effect of MPL on cAMP degradation. A
      pharmacokinetic/pharmacodynamic model was developed based on receptor/gene
      mechanisms of CS action. It successfully described the dual effects of MPL on
      regulating PEPCK message and the post-transcriptional control by cAMP. Our
      results exemplify the importance of the extent and duration of steroid exposure
      in mediating pharmacological effects. The model provides quantitation of multiple
      controlling factors regulating PEPCK and presents insights into its function in
      glucose metabolism.

PMID- 14722325
TI  - Estrogen and progesterone prevent disruption of prepulse inhibition by the
      serotonin-1A receptor agonist 8-hydroxy-2-dipropylaminotetralin.
AB  - The aim of the present study was to investigate the effect of estrogen and
      progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT(1A)) receptor
      mediated disruption of prepulse inhibition (PPI) of acoustic startle. The age-at
      onset of schizophrenia is later in women than men, and it has been suggested that
      women may be protected from schizophrenia by the sex steroid hormone estrogen. 5
      HT(1A) receptors have been implicated in the development of schizophrenia and the
      action of antipsychotics. PPI is a model of sensorimotor gating that is deficient
      in schizophrenia and other illnesses. Female Sprague-Dawley rats were
      ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants
      filled with a low dose of estrogen (E20), a high dose of estrogen (E100),
      progesterone (P), or both the E20- and P-filled (E/P) silastic implants. Two
      weeks later, the rats were randomly treated with saline, or 0.02 or 0.5 mg/kg of
      the 5-HT(1A) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT).
      Treatment with 8-OH-DPAT resulted in a dose-dependent increase in startle
      amplitude in all rat groups. PPI was significantly reduced after injection of 0.5
      mg/kg 8-OH-DPAT in sham-operated rats, untreated OVX rats, E20-treated OVX rats,
      and P-treated OVX rats. In contrast, in E100- and E/P-treated OVX rats, PPI was
      not significantly reduced by 0.5 mg/kg 8-OH-DPAT. These data suggest that
      treatment with a high dose of estrogen, or with a combination of estrogen and
      progesterone, prevents 8-OH-DPAT-induced disruption of PPI. Thus, these hormones
      could be protective against sensorimotor gating deficits, at least those induced
      by 5-HT(1A) receptor stimulation, and may therefore be beneficial against some
      symptoms of schizophrenia.

PMID- 14722326
TI  - Effects of a novel cardioselective ATP-sensitive potassium channel antagonist, 1
      [[5-[2-(5-chloro-o-anisamido)ethyl]-beta-methoxyethoxyphenyl]sulfonyl]-3
      methylthiourea, sodium salt (HMR 1402), on susceptibility to ventricular
      fibrillation induced by myocardial ischemia: in vitro and in vivo studies.
AB  - In the present study, a novel sulfonylthiourea, 1-[[5-[2-(5-chloro-o
      anisamido)ethyl]-beta-methoxyethoxyphenyl]sulfonyl]-3-methylthiourea, sodium salt
      (HMR 1402), was investigated using in vitro and in vivo systems. HMR 1402
      inhibited rilmakalim-induced currents in rat and guinea pig myocytes (IC(50) = 60
      and 509 nM, respectively). Hypoxia-induced shortening of action potential
      duration at 90% repolarization was also significantly attenuated by HMR 1402
      (68.1 +/- 3.9% of control at 0.3 microM). In contrast, HMR 1402 had a smaller
      effect on pancreatic beta-cells (rat insuloma cells, RINm5F) hyperpolarized with
      100 microM diazoxide (IC(50) = 3.9 microM, compared with glibenclamide IC(50) = 9
      nM). In a similar manner, hypoxia induced increases in coronary flow in isolated
      guinea pig hearts were only slightly reduced by HMR 1402. These data strongly
      suggest that HMR 1402 has pharmacological selectivity for cardiac myocytes and,
      therefore, may protect against ischemically induced ventricular fibrillation (VF)
      without the untoward effects of nonselective compounds. To test this hypothesis,
      VF was induced in 8 dogs with healed myocardial infarctions by a 2-min coronary
      occlusion during the last minute of exercise. On a subsequent day, the exercise
      plus ischemia test was repeated after HMR 1402 (3.0 mg/kg i.v., n = 4, infusion 4
      microg/kg/min for 1 h before exercise, n = 4). This drug significantly reduced
      the incidence of VF protecting seven of eight animals (p = 0.0007) without
      altering plasma insulin, blood glucose, or the increases in mean coronary blood
      flow induced by either exercise or 15-s coronary occlusions. Thus, the ATP
      sensitive potassium channel antagonist HMR 1402 can prevent ischemically induced
      VF without altering coronary blood flow or blood glucose.

PMID- 14722327
TI  - Paroxetine inhibits acute effects of 3,4-methylenedioxymethamphetamine on the
      immune system in humans.
AB  - The effect of pretreatment with paroxetine on cell-mediated immune response and
      release of cytokines after the administration of 3,4
      methylenedioxymethamphetamine (MDMA, "ecstasy") was investigated in a double
      blind, randomized, crossover, controlled clinical trial in which 12 healthy male
      recreational users of MDMA participated. Subjects received 20 mg/day paroxetine
      (or placebo) for the 3 days before MDMA challenge (100 mg). Acute MDMA
      administration produced a time-dependent decrease in CD4 T-helper cells, a
      decrease in the functional responsiveness of lymphocytes to mitogenic
      stimulation, a simultaneous increase in natural killer (NK) cells as well as
      cortisol and prolactin stimulation kinetics. A high increase in the release of
      anti-inflammatory cytokines (transforming growth factor-beta and interleukin-10)
      with a simultaneous decrease of anti-inflammatory response (interleukin-2) was
      also observed. Pretreatment with paroxetine partially reduced MDMA effects on CD4
      T and NK cells, whereas totally inhibiting the suppression of the immune response
      to mitogens and alterations in cytokines release. MDMA-induced alterations in the
      immune system as well as antagonistic effects mediated by paroxetine show a trend
      toward baseline levels at 24 h. These findings suggest that acute effects of MDMA
      on immune system are mainly mediated by its interaction with the serotonin
      transporter and subsequent serotonin release with a possible participation of
      other neuroendocrine regulatory systems.

PMID- 14722328
TI  - Inhibitors of tryptase as mast cell-stabilizing agents in the human airways:
      effects of tryptase and other agonists of proteinase-activated receptor 2 on
      histamine release.
AB  - Tryptase, the major secretory product of human mast cells, is emerging as a new
      target for therapeutic intervention in allergic airways disease. We have
      investigated the ability of tryptase and inhibitors of tryptase to modulate
      histamine release from human lung mast cells and have examined the potential
      contribution of proteinase-activated receptor 2 (PAR2). The tryptase inhibitor
      APC366 [N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride] was
      highly effective at inhibiting histamine release stimulated by anti-IgE antibody
      or calcium ionophore from enzymatically dispersed human lung cells. A
      concentration of APC366 as low as 10 microM was able to inhibit anti-IgE
      dependent histamine release by some 50%. Addition of leupeptin or the tryptic
      substrate N-benzoyl-D,L-arginine-p-nitroanilide also inhibited IgE-dependent
      histamine release. Purified tryptase in the presence of heparin stimulated a
      small but significant release of histamine from lung cells, suggesting that
      tryptase may provide an amplification signal from activated cells that may be
      susceptible to proteinase inhibitors. Trypsin was also able to induce histamine
      release apparently by a catalytic mechanism. Moreover, pretreatment of cells with
      metabolic inhibitors or with pertussis toxin reduced responses, indicating a
      noncytoxic pertussis toxin-sensitive G protein-mediated signaling process.
      Addition to cells of the PAR2 agonists SLIGKV-NH(2) or tc-LIGRLO-NH(2) or
      appropriate control peptides were without effect on histamine release, and PAR2
      was not detected by immunohistochemistry in tissue mast cells. The potent actions
      of tryptase inhibitors as mast cell-stabilizing agents could be of value in the
      treatment of allergic inflammation of the respiratory tract, possibly by
      targeting the non-PAR2-mediated actions of tryptase.

PMID- 14722329
TI  - Delta-opioid agonists: differential efficacy and potency of SNC80, its 3-OH
      (SNC86) and 3-desoxy (SNC162) derivatives in Sprague-Dawley rats.
AB  - The diarylpiperazine delta-opioid agonist SNC80 [(+)-4-[(alphaR)-alpha-[(2S,5R)
      2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N
      diethylbenzamide] produces convulsions, antidepressant-like effects, and
      locomotor stimulation in rats. The present study compared the behavioral effects
      in Sprague-Dawley rats of SNC80 with its two derivatives, SNC86 [(+)-4-[alpha(R)
      alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3
      hydroxyphenyl)methyl]-N,N-diethylbenzamide] and SNC162 [(+)-4-[(alphaR)-alpha
      [(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N
      diethylbenzamide], which differ by one functional group located in the 3-position
      of the benzylic ring. In behavioral measures, these three compounds demonstrated
      a rank order of potency and efficacy; SNC86 was the most potent and efficacious
      followed by SNC80 and then SNC162. In vitro, these compounds stimulated guanosine
      5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in the caudate
      putamen of coronal brain slices from drug-naive rats as measured by in vitro
      autoradiography. In [(35)S]GTPgammaS binding studies, SNC86 seemed to be a full
      agonist at the delta-opioid receptor; however, SNC162 demonstrated reduced
      stimulation compared with SNC86, consistent with partial agonist activity.
      Although SNC80 was not fully efficacious in [(35)S]GTPgammaS autoradiography
      studies, it produced behavioral effects similar to those observed with SNC86,
      suggesting that the behavioral effects of SNC80 may be produced by its 3-hydroxy
      metabolite.

PMID- 14722330
TI  - SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo
      2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride):
      a new selective and orally active oxytocin receptor antagonist for the prevention
      of preterm labor.
AB  - 4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro
      1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)benzamide, hydrochloride (SSR126768A),
      a new potent and selective, orally active oxytocin (OT) receptor antagonist was
      characterized in several biochemical and pharmacological models. In binding
      studies, SSR126768A showed nanomolar affinity for rat and human recombinant and
      native OT receptors (K(i) = 0.44 nM) and exhibited much lower affinity for V(1a),
      V(1b), and V(2) receptors. In addition, it did not interact with a large number
      of other receptors, enzymes, and ion channels (1 microM). In autoradiographic
      experiments performed on at-term human pregnant uterus sections, SSR126768A dose
      dependently displaced [I(125)]d(CH(2))(5)[Tyr(Me)(2), Thr(4), Orn(8) (125)I-Tyr
      NH(2)(9)]VT in situ labeling to OT receptors highly expressed in these tissues.
      In functional studies, SSR126768A behaved as a full antagonist and potently
      antagonized OT-induced intracellular Ca(2+) increase (K(i) = 0.50 nM) and
      prostaglandin release (K(i) = 0.45 nM) in human uterine smooth muscle cells. In
      rat isolated myometrium, OT-induced uterine contractions were competitively
      antagonized by SSR126768A (pA(2) = 8.47). Similarly, in human pregnant myometrial
      strips, SSR126768A inhibited the contractile uterine response to OT. In conscious
      telemetrated rats, oral administration of SSR126768A (1-10 mg/kg) produced a
      competitive inhibition of the dose response to OT on uterine contractions up to
      24 h at 3 mg/kg p.o.; no tachyphylaxis was observed after 4-day repeated
      treatment. Finally, SSR126768A (30 mg/kg p.o.) significantly delayed parturition
      in pregnant rats in labor similar to ritodrine (10 mg/kg p.o.). Thus, SSR126768A
      is a potent, highly selective, orally active OT receptor antagonist with a long
      duration of action. This molecule could find therapeutic application as a
      tocolytic agent for acute and chronic oral management of preterm labor.

PMID- 14722332
TI  - Predictors of subjective memory in older adults.
AB  - Memory complaints by healthy older people usually show little relation to
      objective memory performance. If subjective memory evaluations are not driven by
      actual memory problems, what is the cause of these complaints? Correlations of an
      objective measure of memory as well as measures of personality, emotional
      distress, and health with subjective memory evaluations were examined in 283
      community-dwelling people aged 45 to 94 years. Stepwise regression analysis
      revealed that a combination of personality measures (Conscientiousness, self
      esteem, Neuroticism) explained about a third of the variance in memory complaints
      compared with only 4% unique variance associated with the objective memory
      measure. Successful interventions for memory concerns in nondemented older people
      need to be tailored to the individual.

PMID- 14722333
TI  - Sentence-final word completion norms for young, middle-aged, and older adults.
AB  - This report describes sentence-final word completion norms for 119 sentence
      contexts based on the original sentence completion norms of Bloom and Fischler
      (1980). Four sets of norms are made available for 358 adults, representing young,
      middle-aged, young-old, and old-old samples. Notable in these norms is a high
      degree of consistency in responses among all four age samples. Differences in
      relation to the original Bloom and Fischler norms appear in responses to low
      contextually constraining sentences. Results show that the recency with which
      normative data are collected is an important variable to consider when making use
      of norms.

PMID- 14722334
TI  - Age-related changes in the functional visual field: further evidence for an
      inverse Age x Eccentricity effect.
AB  - We assessed the performance of younger and older individuals by using the
      Attended Field of View test, a visual search task in which eye movements were
      allowed. When adjusting for slower processing in the older age group by log
      transformation, we observed significant effects of age, eccentricity, and Age x
      Eccentricity. Contrary to most previous findings, the Age x Eccentricity effect
      was "inverted" in that the difference between the age groups decreased as a
      function of eccentricity. The finding that the eccentricity effect of younger
      individuals was larger than that of older individuals was caused by large age
      related differences in sensitivity for centrally located targets, even though
      differences with regard to foveal resolution were controlled. The results further
      indicated that, given a brief amount of time, older persons could process a
      smaller field of view than younger persons. Consequently, older persons were
      forced to resort to serial scanning for a larger part of the display, whereas
      younger persons could process a larger area in parallel.

PMID- 14722335
TI  - The impact of health problems on depression and activities in middle-aged and
      older adults: age and social interactions as moderators.
AB  - In this study, we compared the impact of health problems (HPs) on everyday
      activities and depressive symptoms between middle-aged and older adults. We also
      examined what type and source of social interactions moderate the noxious effects
      of HPs. Longitudinal analyses of data with 1,802 Japanese community-dwelling
      adults indicated that HPs were significantly related to (a) an increase in
      depressive symptoms among middle-aged adults and (b) a decline in everyday
      activities among older adults. The former was buffered by emotional family
      support, whereas the latter (b) was buffered by instrumental family support and,
      surprisingly, by negative interactions with family. In contrast, social
      interactions with other friends and acquaintances did not show any moderating
      effect.

PMID- 14722336
TI  - Effects of a caregiver intervention on negative caregiver appraisals of behavior
      problems in patients with Alzheimer's disease: results of a randomized trial.
AB  - Behavioral problems are among the most challenging aspects of caring for a person
      with Alzheimer's disease. A sample of 406 spouses-caregivers of patients with
      Alzheimer's disease was randomized to an active multicomponent counseling and
      support intervention condition or to a usual care condition. Caregivers reported
      on the frequency of troublesome patient behaviors and their reactions to them at
      baseline and at regular follow-up interviews. Random-effects regression models
      over the first 4 years after randomization revealed that, although the
      intervention did not affect the frequency of patient behavioral problems, it did
      significantly reduce caregivers' reaction ratings. Because caregiver appraisals
      have been found to mediate the impact of caregiving stress on depression and to
      predict nursing home placement rates, they deserve greater attention as an
      important target of intervention services.

PMID- 14722337
TI  - Adaptation to disability among middle-aged and older adults: the role of
      assimilative and accommodative coping.
AB  - The purpose of this study was to investigate the links among coping, disability,
      and mental health among adults who are confronted with age-related vision loss.
      Drawing on the model of assimilative and accommodative coping (e.g.,
      Brandtstadter, 1999), hierarchical regressions were designed to examine the
      effects of coping and disability on mental health. Participants were 55 middle
      aged and 52 older adults who had been recruited from a community-based
      rehabilitation agency. Findings demonstrate a critical role of accommodative
      coping for adaptation, with beneficial effects on mental health that were more
      pronounced in the case of high disability for younger participants. Finally,
      findings suggest that dealing with disability may pose more of a mental health
      risk in middle than in late adulthood.

PMID- 14722338
TI  - Marital implications of parent-adult child coresidence: a longitudinal view.
AB  - OBJECTIVES: This study assesses implications of changes in coresidence with adult
      children for parents' marital relations, hypothesizing that transitions into
      coresidence lower marital quality and transitions out of coresidence increase
      marital quality. METHODS: Panel data from Waves 1 and 2 of the National Survey of
      Families and Households are used to analyze whether change in three measures of
      marital quality-time together, happiness, and disagreements-is related to adult
      child coresidence. RESULTS: When adult children move out, parent couples increase
      their time together; there is a tendency for reduced time together when the nest
      "refills." However, there are no effects of moves in or out on the marital
      happiness of parents or the number of marital disagreements they have. There is
      also no effect on time together or on marital quality when one adult child moves
      out but another moves in during the same period. The presence of younger children
      has more consistent associations with marital quality. DISCUSSION: Coresidence
      with adult children does not appear to be an experience that disrupts the quality
      of marital relations. It may be that qualitative dimensions of coresidence
      experiences with adult children matter more than coresidence per se.

PMID- 14722339
TI  - Grandparenthood: factors influencing frequency of grandparent-grandchildren
      contact and grandparent role satisfaction.
AB  - OBJECTIVES: Symbolic interaction theory suggests that self processes motivate
      individual behaviors and responses to roles. In this study, we explore the
      influence of self processes on grandparenthood. METHODS: Data were collected in
      1997 from 203 middle-aged grandmothers and grandfathers living in the Raleigh
      Durham-Chapel Hill, North Carolina, metropolitan area. We are especially
      interested in whether three self factors, grandparent identity meanings,
      grandparent centrality, and self-esteem, are related to frequency of contact with
      grandchildren and grandparent role satisfaction. RESULTS: Results indicate that
      there are gender differences in the factors that influence the frequency of
      contact between grandparents and grandchildren. The self variables influenced
      frequency of contact for grandfathers but not for grandmothers. Stronger support
      for our expectation emerged in the analysis of factors that influence grandparent
      satisfaction. All three self factors are positively related to grandparent role
      satisfaction for both grandmothers and grandfathers. DISCUSSION: More research is
      needed on the expectations and experiences of the grandparent role. In this
      study, we focused attention on self processes. The finding that grandparent
      identity meanings, grandparent centrality, and self-esteem influence grandparent
      role satisfaction suggests that self factors should be included in comprehensive
      investigations of grandparenthood. The next step is to explore the grandparent
      identity in more detail and investigate how it relates to other identities and to
      the well-being of older persons.

PMID- 14722340
TI  - Themes of suffering in later life.
AB  - OBJECTIVES: This qualitative research study explored the personal meaning of
      suffering to a group of 40 community-dwelling elders, stratified by gender and
      race. METHODS: We recruited 40 informants who were 70 years old or older from the
      Philadelphia, PA, area for extended qualitative interviews, which elicited their
      life story and experiences and philosophies about suffering. Cells contained 10
      African American men and women and 10 European American men and women each (N =
      40). Through analysis of data, we placed elders' experiences of suffering under
      three general themes: suffering as lack of control, suffering as loss, and the
      value of suffering. RESULTS: Informants developed a unique definition,
      attribution, theory, and theodicy about suffering based on the particularity of
      the experience as well as how they "fit" suffering into their lives as a whole.
      Brief case studies illustrate how themes emerged in elders' stories of suffering.
      DISCUSSION: On the basis of this research, it appears that, although they have
      some similarities, elders' experiences of suffering are unique and incomparable.
      Similarities concern informants' connection of suffering with finitude. The
      incomparability of suffering experiences relate to informants' unique personal
      histories, perceptions, and "cause" of suffering. Through the process of the
      interview, elders connect the suffering experience to the entirety of the life
      lived and the story of suffering to the life story.

PMID- 14722341
TI  - Disability and home care dynamics among older unmarried Americans.
AB  - OBJECTIVES: We describe how paid and unpaid home care hours received by older
      unmarried Americans change in response to disability dynamics. We test whether
      responses to disability declines and improvements are symmetric; that is, we test
      whether reductions in care hours that are due to disability improvements are of
      similar magnitude to increases in care hours that are due to disability declines.
      METHODS: Using a national sample of older unmarried Americans, we examine changes
      in total hours, paid hours, and unpaid hours of care in response to declines and
      improvements in personal care (activities of daily living, or ADLs) and routine
      care (instrumental ADLs, or IADLs) disability. We model changes in the total
      hours of care received in the past month and jointly model changes in unpaid and
      paid hours, using Tobit models. RESULTS: Changes in the total hours of care
      received respond to both increases and decreases in the count of ADL limitations
      and appear close to symmetric. In contrast, responses to IADL disability dynamics
      appear to be far less symmetric: Although increases in the count of IADL
      limitations are met with substantial increases in the total hours of care,
      decreases are not met with correspondingly large declines in care. The same
      general pattern is found for unpaid and paid care, and for Medicaid-funded home
      care. DISCUSSION: Disability and care are not static constructs in old age. Older
      unmarried persons experience worsening, stabilizing, and recovery of function,
      and their care hours change accordingly. Evaluations of home care programs must
      be cognizant of such dynamic realities.

PMID- 14722342
TI  - The black/white disability gap: persistent inequality in later life?
AB  - OBJECTIVES: Previous research on differences between Black and White older adults
      has produced inconsistent results on whether a gap in disability exists and
      whether it persists over time. The present research identifies several reasons
      for the inconsistent results to date and examines Black/White differences in
      disability trajectories over 6 years. METHODS: Data from the North Carolina
      Established Populations for the Epidemiologic Studies of the Elderly (1986-1992)
      are used to estimate the disability gap and trajectory over time for both Black
      and White older adults. RESULTS: Results indicate that a disability gap between
      Black and White adults exists, but after socioeconomic resources, social
      integration, and other health indicators are adjusted for, the trajectories of
      disability by race are not significantly different. Controlling for incident
      morbidity over time accounts for the significant difference in level of
      disability between the two groups. DISCUSSION: This research supports the
      "persistent inequality" interpretation, indicating that Black adults have higher
      morbidity and disability earlier in life compared with White adults, and that the
      gap neither converges nor diverges over time.

PMID- 14722343
TI  - The impact of structural and functional characteristics of social relations as
      determinants of functional decline.
AB  - OBJECTIVES: This study examines whether aspects of social relations at baseline
      are related to functional decline at 5-year follow-up among nondisabled old men
      and women. METHODS: The investigation is based on baseline and follow-up data on
      651 nondisabled 75-year-old persons in Jyvaskyla (Finland) and Glostrup
      (Denmark). The analyses are performed separately for men and women. Possible
      selection problems were considered by using three outcome measures: first,
      functional decline among the survivors (n = 425); second, functional decline,
      including death, assuming that death is part of a general decline pattern (n =
      565); and third, mortality (n = 651). Social relations were measured at baseline
      by several items focusing on the structure and function of the social network.
      RESULTS: In men, no weekly telephone contact was related to functional decline
      and mortality. Among women, less than weekly telephone contact, no membership in
      a retirement club, and not sewing for others were significantly related to
      functional decline and mortality. The associations were stronger when the dead
      were included in the outcome measure. DISCUSSION: The results point to the
      importance of social relations in the prevention of functional decline in older
      adults.

PMID- 14722344
TI  - Inverse agonists: tools to reveal ligand-specific conformations of G protein
      coupled receptors.
AB  - G protein-coupled receptors (GPCRs) traverse the plasma membrane seven times and
      produce intracellular effects through interaction with G proteins. Three classes
      of ligands bind and regulate the activity of GPCRs: agonists, antagonists, and
      inverse agonists. To describe the activity of these ligands at GPCRs, a two-state
      receptor model has been proposed in which receptors exist in an equilibrium
      between inactive (R) and active (R*) states. Agonists preferentially bind and
      stabilize the active (R*) state. This results in an enrichment of the proportion
      of active receptors, producing an increase in receptor activity. In contrast,
      inverse agonists preferentially bind and stabilize receptors in the inactive (R)
      state. This results in an enrichment of the proportion of inactive receptors,
      producing a reduction in spontaneous receptor activity. Neutral antagonists have
      equal preferences for both R and R* states, lack any intrinsic activity, and are
      able to block actions produced by either agonists or inverse agonists. Exciting
      observations reported in two recent manuscripts by Gbahou et al. and Azzi et al.
      indicate that some inverse agonists act not only in opposition to agonists by
      suppressing constitutive receptor activity, but may also initiate unique signal
      transduction cascades as well. Specifically, it is proposed that these unique
      ligands are able to enrich several distinct active receptor conformations, each
      demonstrating a preference for regulation of a discrete intracellular effector.
      This suggests that inverse agonists are not merely "the opposite of agonists,"
      but instead may serve as useful tools to investigate ligand-specific
      conformations of GPCRs.

PMID- 14722345
TI  - Flirting in little space: the ER/mitochondria Ca2+ liaison.
AB  - Mitochondria have long been known to accumulate Ca2+; the apparent inconsistency
      between the low affinity of mitochondrial Ca2+ uptake mechanisms, the low
      concentration of global Ca2+ signals observed in cytoplasm, and the efficiency in
      intact cells of mitochondrial Ca2+ uptake led to the formulation of the "hotspot
      hypothesis." This hypothesis proposes that mitochondria preferentially accumulate
      Ca2+ at microdomains of elevated Ca2+ concentration ([Ca2+]) that exist near
      endoplasmic reticulum (ER) Ca2+ release sites and other Ca2+ channels.
      Physiological Ca2+ signals may affect mitochondrial function--both by stimulating
      key metabolic enzymes and, under some conditions, by promoting apoptosis.
      Mitochondria in turn may affect both Ca2+ release from the ER and capacitative
      Ca2+ entry across the plasma membrane, thereby shaping the size and duration of
      the intracellular Ca2+ signal. Interactions between mitochondria and the ER are
      critically dependent on the spatial localization of mitochondria within the cell.
      The molecular mechanisms that define the organization of mitochondria with regard
      to the ER and other Ca2+ sources, and the extent to which mitochondrial function
      varies among different cell types, are open questions whose answers remain to be
      determined.

PMID- 14722346
TI  - Orthopaedic intervention in early rheumatoid arthritis. Occurrence and predictive
      factors in an inception cohort of 1064 patients followed for 5 years.
AB  - OBJECTIVES: To assess the occurrence of and predictive factors for orthopaedic
      surgery in an inception cohort of rheumatoid arthritis (RA) patients recruited
      and followed prospectively for 5 yr in nine regions in England. METHODS: Standard
      clinical, laboratory and radiological assessments and all interventions were
      recorded at baseline and yearly in RA patients (less than 2 yrs symptoms) prior
      to the use of disease-modifying drugs. RESULTS: One thousand and sixty-four
      patients completed 5 yr of follow-up. Two hundred and sixty-four orthopaedic
      procedures for RA were performed in 181 (17%) patients at a median of 36.5 months
      from baseline. Seventy-five (7%) had replacements of major joints. Risk factors
      at baseline for large joint replacement surgery were a low haemoglobin
      concentration [odds ratio scores (OR) 3.4, 95% confidence interval (CI) 2.1-5.8]
      and high scores for erythrocyte sedimentation rate (ESR) (OR 3.2, CI 1.8-5.3),
      disease activity (DAS) (OR 2.1, CI 1.2-3.5) and Larsen X-rays (OR 2.6, CI 1.4
      4.8). For hand or foot joint surgery (4%), risk factors included female gender
      (OR 3.2, CI 1.3-7.6), joint score (OR 2.3, CI 1.2-4.3), erosions (OR 2.3, CI 1.1
      4.8), DAS (OR 2.4, 1.3-4.5) and Health Assessment Questionnaire score (OR 1.9, CI
      1.0-3.6). No significant associations were seen for tendon, soft tissue or other
      minor procedures (6%). The HLA-DRB1 RA shared epitope was associated with any
      type of orthopaedic surgery (OR 1.7, CI 1.1-2.7). CONCLUSIONS: Eleven per cent of
      RA patients treated with conventional drug therapy for 5 yr underwent large- or
      small-joint surgery, an outcome which could be compared against that for new
      disease-modifying drugs. Risk factors varied according to type of surgery, but
      included standard clinical and laboratory measures. In order to reduce the
      eventual need for surgery, a therapeutic target in the first year of RA is the
      suppression of disease activity, as measured by haemoglobin and ESR. These are
      useful details for clinicians, health professionals and patients.

PMID- 14722347
TI  - Bone turnover in untreated polymyalgia rheumatica.
AB  - BACKGROUND: Polymyalgia rheumatica (PMR) is a common condition in the elderly. A
      previous study demonstrated that it is associated with an increase in bone
      resorption. This effect was ameliorated by steroids, implying that inflammation
      is the cause of increased bone resorption and that this can be reduced by
      steroids. This is in keeping with accumulating evidence that systemic
      inflammation is associated with bone resorption and bone loss. We studied bone
      formation and resorption markers in 53 patients with PMR prior to any therapeutic
      intervention. METHODS: Bone resorption was measured by estimating urinary free
      pyridinoline (fPYD) and deoxypyridinoline (fDPD). Bone formation was estimated by
      measuring serum concentrations of procollagen type 1 N-terminal propeptide
      (P1NP). Disease activity was assessed using inflammatory markers (erythrocyte
      sedimentation rate and C-reactive protein). Patients had a baseline dual-energy X
      ray absorptiometer scan to assess bone mineral density. RESULTS: Bone resorption
      markers were significantly increased and bone formation markers significantly
      decreased in PMR patients prior to treatment, compared with a control population
      matched for gender and age. CONCLUSIONS: This implies that bone turnover is
      uncoupled in PMR. This may lead to a decrease in skeletal mass in the long term
      due to the disease process alone. However, no significant loss of bone mineral
      density was detected. It is possible that, due to the acute onset of PMR,
      increased bone resorption is not present long enough to result in a detectable
      decrease in bone mineral density. The effects of steroid treatment on bone
      metabolism and the subsequent long-term outcome need to be investigated.

PMID- 14722348
TI  - The reliability, validity and responsiveness of an aggregated locomotor function
      (ALF) score in patients with osteoarthritis of the knee.
AB  - OBJECTIVES: The aggregated locomotor function (ALF) score, a simple measure of
      observed locomotor function, using timed walking, stairs and transfers, was
      developed and evaluated for intra-tester reliability, criterion-related validity
      and responsiveness in a sample of patients with knee osteoarthritis. METHODS:
      Patients with knee osteoarthritis (n = 214) were recruited for inclusion in a
      randomized controlled trial investigating two methods of exercise provision.
      Before treatment, patients completed the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) and Short Form 36 health survey (SF-36)
      questionnaires and were timed whilst performing an 8 m walk, ascending and
      descending a set of gymnasium stairs and completing a test of transferring in and
      out of a chair. A group of 15 patients also undertook a replicate test-retest
      reliability study of the above outcome measures. Standardized response means were
      calculated for the ALF, WOMAC and SF-36 from data from the clinical trial.
      RESULTS: The ALF takes 10 min to administer and demonstrated excellent intra
      tester reliability, with excellent intra-class correlation coefficient (ICC)
      statistics (ICC(2,k) 0.99; 95% CI 0.98-0.99), and low standard error of
      measurement (0.86 s) and smallest detectable difference (9.5%) values. Criterion
      related validity with the physical function dimensions of the WOMAC and SF-36 was
      good, with correlation coefficients of 0.59 and - 0.53 respectively. Standardized
      response means were higher for the ALF (0.49) than for both the WOMAC (0.39) and
      the SF-36 (0.12). CONCLUSIONS: This work has demonstrated that the ALF can be
      used as a measure of physical function status and as a means of quantifying
      treatment response. The measure offers a simple and convenient outcome in the
      assessment and treatment of locomotor dysfunction. The ALF score is a reliable,
      valid and responsive outcome measure over 12 months and can be recommended for
      use in the evaluation of patients with knee osteoarthritis.

PMID- 14722349
TI  - Intravenous cyclophosphamide pulse therapy in juvenile dermatomyositis. A review
      of efficacy and safety.
AB  - OBJECTIVES: To assess the efficacy and safety of intravenous cyclophosphamide
      (CYP) used in severe and refractory juvenile dermatomyositis (JDM). METHODS:
      Retrospective case note review of the outcome of 12 patients. RESULTS: Assessment
      at 6 months of therapy in 10 of the 12 patients showed a significant improvement
      in muscle function as assessed by the Childhood Myositis Assessment Scale (CMAS)
      (P = 0.012), muscle strength (P = 0.008), global extramuscular disease score (P =
      0.008), skin disease severity (P = 0.015) and lactate dehydrogenase (P = 0.028).
      There were reductions in creatine kinase, alanine aminotransferase, prednisolone
      dose and ESR, but these did not reach statistical significance. Clinical
      improvement was maintained after CYP until the most recent follow-up (between 6
      months and 7 yr) and no severe side-effects were seen. Reversible complications
      included lymphopenia, herpes zoster infections and alopecia. The median
      cumulative dose was 4.6 g/m(2) (range 3-9 g/m(2)). The available evidence
      suggests that, at the doses required, risks of malignancy, infertility and
      gonadal failure are low. Two patients with severe treatment-resistant disease
      died after one dose of CYP, both of whom were ventilated prior to commencement of
      CYP and were thought to have died as a result of their severe disease process,
      and too early for clinical benefit to be obtained from the drug. CONCLUSIONS: In
      this cohort of children with severe and refractory JDM, CYP appeared to have
      provided major clinical benefit with no evidence of serious toxicity in the short
      term.

PMID- 14722350
TI  - Gout complicated with necrotizing fasciitis--report of 15 cases.
AB  - OBJECTIVE: To analyse the clinical features and outcomes of gout complicated with
      necrotizing fasciitis. METHODS: From the database of our hospital, we identified
      15 hospitalized cases of gout complicated with necrotizing fasciitis from 1987 to
      2001. The medical records of the patients were analysed in detail. RESULTS: Mean
      patient age was 54.7 +/- 12.8 yr. Fever was found in only 10 (66.7%) patients,
      while the remaining five patients were afebrile on presentation. The peripheral
      blood white count was raised in only nine (60%) patients. The median time from
      the onset of symptoms to hospital visit was 4 days (range 2 to 25). Formation of
      bullae occurred in 60% of patients. Six patients had previous wound infection,
      two patients had concomitant septic arthritis and the remaining seven patients
      had no obvious source of infection. Diabetes mellitus and iatrogenic Cushing
      syndrome were each found in three patients. The identified causative
      microorganisms were Gram-positive cocci (eight cases) and Gram-negative bacilli
      (four cases); but in three patients the causative organisms were unknown.
      Thirteen patients received surgery, including amputation in four cases. Finally,
      six patients suffered septic shock, three of whom died as a result. CONCLUSIONS:
      Necrotizing fasciitis in gout patients represents a surgical and medical
      emergency, and is associated with a high mortality rate. Prompt diagnosis and
      treatment is imperative and may be lifesaving. Early diagnosis requires a high
      level of suspicion, even in patients without fever or leucocytosis.

PMID- 14722351
TI  - In silico dissection of cell-type-associated patterns of gene expression in
      prostate cancer.
AB  - Prostate tumors are complex entities composed of malignant cells mixed and
      interacting with nonmalignant cells. However, molecular analyses by standard gene
      expression profiling are limited because spatial information and nontumor cell
      types are lost in sample preparation. We scored 88 prostate specimens for
      relative content of tumor, benign hyperplastic epithelium, stroma, and dilated
      cystic glands. The proportions of these cell types were then linked in silico to
      gene expression levels determined by microarray analysis, revealing unique cell
      specific profiles. Gene expression differences for malignant and nonmalignant
      epithelial cells (tumor versus benign hyperplastic epithelium) could be
      identified without being confounded by contributions from stroma that dominate
      many samples or sacrificing possible paracrine influences. Cell-specific
      expression of selected genes was validated by immunohistochemistry and
      quantitative PCR. The results provide patterns of gene expression for these three
      lineages with relevance to pathogenetic, diagnostic, and therapeutic
      considerations.

PMID- 14722352
TI  - A functional cellulose synthase from ascidian epidermis.
AB  - Among animals, urochordates (e.g., ascidians) are unique in their ability to
      biosynthesize cellulose. In ascidians cellulose is synthesized in the epidermis
      and incorporated into a protective coat know as the tunic. A putative cellulose
      synthase-like gene was first identified in the genome sequences of the ascidian
      Ciona intestinalis. We describe here a cellulose synthase gene from the ascidian
      Ciona savignyi that is expressed in the epidermis. The predicted C. savignyi
      cellulose synthase amino acid sequence showed conserved features found in all
      cellulose synthases, including plants, but was most similar to cellulose
      synthases from bacteria, fungi, and Dictyostelium discoidium. However, unlike
      other known cellulose synthases, the predicted C. savignyi polypeptide has a
      degenerate cellulase-like region near the carboxyl-terminal end. An expression
      construct carrying the C. savignyi cDNA was found to restore cellulose
      biosynthesis to a cellulose synthase (CelA) minus mutant of Agrobacterium
      tumefaciens, showing that the predicted protein has cellulose synthase activity.
      The lack of cellulose biosynthesis in all other groups of metazoans and the
      similarity of the C. savignyi cellulose synthase to enzymes from cellulose
      producing organisms support the hypothesis that the urochordates acquired the
      cellulose biosynthetic pathway by horizontal transfer.

PMID- 14722353
TI  - Global optimization of cerebral cortex layout.
AB  - Functional areas of mammalian cerebral cortex seem positioned to minimize costs
      of their interconnections, down to a best-in-a-billion optimality level. The
      optimization problem here, originating in microcircuit design, is: Given
      connections among components, what is the physical placement of the components on
      a surface that minimizes total length of connections? Because of unfeasibility of
      measuring long-range "wire length" in the cortex, a simpler adjacency cost was
      validated. To deal with incomplete information on brain networks, a size law was
      developed that predicts optimization patterns in subnetworks. Macaque and cat
      cortex rank better in this connection optimization than the wiring of comparably
      structured computer chips, but somewhat worse than the macroeconomic commodity
      flow network among U.S. states. However, cortex wiring conforms to the size law
      better than the macroeconomic patterns, which may indicate cortex optimizing
      mechanisms involve more global processes.

PMID- 14722354
TI  - T cell repertoire scanning is promoted by dynamic dendritic cell behavior and
      random T cell motility in the lymph node.
AB  - Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph
      nodes where they present MHC class II-bound antigen to CD4(+) T cells. We used
      two-photon microscopy to image the single-cell dynamics of interactions between
      DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs
      were fluorescently labeled in vivo by cutaneous injection of alum adjuvant
      including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive
      DCs (CD11c(+), CD11b(+), and low-to-intermediate CD8(+)) were observed in
      draining lymph nodes 24-72 h later. Labeled DCs meandered slowly (2-3 microm x
      min(-1)) in the T cell zone near B cell follicles but vigorously extended long
      agile dendrites. Encounters between T cells and DCs arose as T cells moved
      autonomously along random paths. Moreover, T cells did not accumulate around DCs,
      and their relative velocities approaching and departing DCs were equivalent,
      implying that T cells are not attracted toward DCs by chemotactic gradients but
      rather encounter them by chance. T cell/DC contacts occurred primarily on
      dendrites at arm's length from the DC soma and typically lasted approximately 3
      min, enabling an individual DC to interact with up to 5000 T cells per hour. We
      conclude that dynamic DC gesticulation and random T cell motility together
      enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid
      initiation of the immune response.

PMID- 14722355
TI  - A serine protease zymogen functions as a pattern-recognition receptor for
      lipopolysaccharides.
AB  - Bacterial lipopolysaccharide (LPS)-induced exocytosis of granular hemocytes is a
      key component of the horseshoe crab's innate immunity to infectious
      microorganisms; stimulation by LPS induces the secretion of various defense
      molecules from the granular hemocytes. Using a previously uncharacterized assay
      for exocytosis, we clearly show that hemocytes respond only to LPS and not to
      other pathogen-associated molecular patterns, such as beta-1,3-glucans and
      peptidoglycans. Furthermore, we show that a granular protein called factor C, an
      LPS-recognizing serine protease zymogen that initiates the hemolymph coagulation
      cascade, also exists on the hemocyte surface as a biosensor for LPS. Our data
      demonstrate that the proteolytic activity of factor C is both necessary and
      sufficient to trigger exocytosis through a heterotrimeric GTP-binding protein
      mediating signaling pathway. Exocytosis of hemocytes was not induced by thrombin,
      but it was induced by hexapeptides corresponding to the tethered ligands of
      protease-activated G protein-coupled receptors (PARs). This finding suggested the
      presence of a PAR-like receptor on the hemocyte surface. We conclude that the
      serine protease zymogen on the hemocyte surface functions as a pattern
      recognition protein for LPS.

PMID- 14722356
TI  - Selection of B lymphocytes in the periphery is determined by the functional
      capacity of the B cell antigen receptor.
AB  - Within the B cell antigen receptor (BCR), the cytoplasmic tails of both Igalpha
      and Igbeta are required for normal B cell development and maturation. To dissect
      the mechanisms by which each tail contributes to development in vivo, Igbeta(-/-)
      mice were reconstituted with retroviruses encoding either wild-type Igbeta, an
      Igbeta molecule lacking a cytoplasmic tail (Igbeta(deltaC)) or one in which the
      cytoplasmic tail was derived from Igalpha (Igbeta(Calpha)). All constructs
      rescued B cell development and generated immature B cell populations in the bone
      marrow with similar expression levels of both Igbeta and membrane-bound IgM. In
      the periphery, receptor-surface density was inversely proportional to the number
      of Igalpha tails in the BCR. Although peripheral-surface-receptor levels
      differed, splenic B cells expressing either Igbeta or Igbeta(Calpha) responded
      similarly to stimulation through the BCR. Analysis of membrane-bound IgM and
      Igbeta expression revealed that peripheral-receptor expression was primarily
      determined by positive selection between the bone marrow and peripheral immature
      B cell populations. These data indicate that B cells are selected into the
      periphery on the basis of a common level of antigen responsiveness.

PMID- 14722357
TI  - Paired-pulse depression of unitary quantal amplitude at single hippocampal
      synapses.
AB  - At central synapses, quantal size is generally regarded as fluctuating around a
      fixed mean with little change during short-term synaptic plasticity. We evoked
      quantal release by brief electric stimulation at single synapses visualized with
      FM 1-43 dye in hippocampal cultures. The majority of quantal events evoked at
      single synapses were monovesicular, based on examination of amplitude
      distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor
      mediated responses. Consistent with previous findings, the quantal size did not
      change during paired-pulse facilitation (PPF), supporting the notion that the
      evoked events were monoquantal. However, during paired-pulse depression (PPD),
      there was a significant decrease in unitary quantal size, which was not due to
      postsynaptic receptor desensitization. This asymmetry of quantal modulation
      during PPF and PPD was demonstrated at the same single synapse at different
      extracellular calcium concentrations. Our results indicate that PPF can be fully
      accounted for by an increase of release probability, whereas PPD may be caused by
      decreases in both release probability and quantal size. One possible explanation
      is that the release of a quantum of neurotransmitter from synaptic vesicles is
      not invariant but subject to rapid calcium-dependent modulation during short-term
      synaptic plasticity.

PMID- 14722358
TI  - Complementation of phytochrome chromophore-deficient Arabidopsis by expression of
      phycocyanobilin:ferredoxin oxidoreductase.
AB  - The covalently bound phytochromobilin (PphiB) prosthetic group is required for
      the diverse photoregulatory activities of all members of the phytochrome family
      in vascular plants, whereas by contrast, green algal and cyanobacterial
      phytochromes use the more reduced linear tetrapyrrole pigment phycocyanobilin
      (PCB). To assess the functional consequence of the substitution of PphiB with PCB
      in plants, the phytochrome chromophore-deficient hy2 mutant of Arabidopsis was
      transformed with a constitutively expressed pcyA gene that encodes the
      cyanobacterial enzyme, PCB:ferredoxin oxidoreductase. Spectroscopic analyses of
      extracts from etiolated seedlings revealed that PcyA expression restored
      photoactive phytochrome to WT levels, albeit with blue-shifted absorption maxima,
      while also restoring light lability to phytochrome A. Photobiological
      measurements indicated that PcyA expression rescued phytochrome-mediated red high
      irradiance responses, low-fluence red/far-red (FR) photoreversible responses, and
      very-low-fluence responses, thus confirming that PCB can functionally substitute
      for PphiB for these photoregulatory activities. Although PcyA expression failed
      to rescue phytochrome A-mediated FR high-irradiance responsivity to that of WT,
      our studies indicate that the FR high-irradiance response is fully functional in
      pcyA-expressing plants but shifted to shorter wavelengths, indicating that PCB
      can functionally complement this phytochrome-mediated response in vascular
      plants.

PMID- 14722359
TI  - Lipid-protein interactions: biosynthetic assembly of CD1 with lipids in the
      endoplasmic reticulum is evolutionarily conserved.
AB  - The CD1 family consists of lipid antigen-presenting molecules, which include
      group I CD1a, CD1b, and CD1c and group II CD1d proteins. Topologically, they
      resemble the classical peptide antigen-presenting MHC molecules except that the
      large, exclusively nonpolar and hydrophobic, antigen-binding groove of CD1 has
      evolved to present cellular and pathogen-derived lipid antigens to specific T
      lymphocytes. As an approach to understanding the biochemical basis of lipid
      antigen presentation by CD1 molecules, we have characterized the natural ligands
      associated with mouse CD1d1 as well as human CD1b and CD1d molecules. We found
      that both group I and II CD1 molecules assemble with cellular
      phosphatidylinositol (PI), which contains heterogeneous fatty acyl chains.
      Further, this assembly occurs within the endoplasmic reticulum. Because the
      structures of the antigen-binding grooves of CD1a and CD1c closely resemble those
      of CD1b and CD1d, we conclude that the assembly of CD1 molecules with PI in the
      endoplasmic reticulum is evolutionarily conserved. These findings suggest that PI
      plays a chaperone-like role in CD1 assembly, possibly to preserve the integrity
      of the antigen-binding groove until CD1 binds antigenic lipids in the endocytic
      pathway.

PMID- 14722360
TI  - The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA
      mediated gene regulation.
AB  - The Arabidopsis HYL1 gene encodes a nuclear double-stranded RNA-binding protein.
      A knockout mutation of the hyl1 gene is recessive and pleiotropic, causing
      developmental abnormalities, increasing sensitivity to abscisic acid, and
      reducing sensitivity to auxin and cytokinin. We report that levels of several
      microRNAs (miRNAs; miR159, -167, and -171) are reduced in homozygous mutant
      plants, and levels of two of three tested target mRNAs are elevated. Conversely,
      the miRNA levels are elevated in plants expressing a HYL1 cDNA from a strong
      promoter, and the corresponding target RNAs are reduced. These changes result
      from alterations in the stability of the target RNAs. However, double-stranded
      RNA-induced posttranscriptional gene silencing is unaffected by the hyl1
      mutation. One-third to one-half of the cellular HYL1 protein is in a
      macromolecular complex, and a GFP-HYL1 fusion protein is found predominantly in
      the nucleus, although it is observed in both nucleus and cytoplasm in some cells.
      Within nuclei, HYL1 is associated with subnuclear bodies and ring-like
      structures. These observations provide evidence that the HYL1 protein is part of
      a nuclear macromolecular complex that is involved in miRNA-mediated gene
      regulation. Because hyl1 mutants show marked abnormalities in hormone responses,
      these results further suggest that miRNA-mediated changes in mRNA stability play
      a vital role in plant hormone signaling.

PMID- 14722363
TI  - Indian Academy of Pediatrics and child abuse and neglect and child labour.

PMID- 14722361
TI  - Short-chain fatty acids stimulate leptin production in adipocytes through the G
      protein-coupled receptor GPR41.
AB  - Leptin is an adipose-derived hormone that regulates a wide variety of
      physiological processes, including feeding behavior, metabolic rate, sympathetic
      nerve activity, reproduction, and immune response. Circulating leptin levels are
      tightly regulated according to energy homeostasis in vivo. Although mechanisms
      for the regulation of leptin production in adipocytes are not well understood, G
      protein-coupled receptors may play an important role in this adipocyte function.
      Here we report that C2-C6 short-chain fatty acids, ligands of an orphan G protein
      coupled receptor GPR41, stimulate leptin expression in both a mouse adipocyte
      cell line and mouse adipose tissue in primary culture. Acute oral administration
      of propionate increases circulating leptin levels in mice. The concentrations of
      short-chain fatty acids required to stimulate leptin production are within
      physiological ranges, suggesting the relevance of this pathway in vivo.

PMID- 14722362
TI  - Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic
      effects: confirmation of a chromosome 6 locus in a congenic strain.
AB  - Atherosclerosis is a complex disease resulting from the interaction of multiple
      genes, including those causing dyslipidemia. Relatively few of the causative
      genes have been identified. Previously, we identified Apoa2 as a major
      determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse
      model. To identify additional HDL-C level quantitative trait loci (QTLs), while
      controlling for the effect of the Apoa2 locus, we performed linkage analysis in
      179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a
      congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one
      suggestive locus were identified. A female-specific locus mapping to chromosome 6
      (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII),
      apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related
      congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and
      non-HDL-C levels, respectively). These data are consistent with polygenic
      inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL
      C and non-HDL-C level determination in humans.

PMID- 14722364
TI  - Effectiveness of nutrition education, iron supplementation or both on iron status
      in children.
AB  - OBJECTIVE: A community-based, randomized trial was designed to compare the effect
      of nutrition education and/or iron supplementation (weekly) on iron status of
      children in an urban slum in Delhi. METHODS: Four hundred and fifty one children,
      9-36 months of age and their caretakers (mothers), assigned to one of the
      following groups were included in the cohort. Group 1, nutrition education. Group
      2, supplementation (with 20 mg elemental iron). Group 3, nutrition education with
      supplementation (with 20 mg elemental iron) and Group 4, control given placebo.
      The intervention program was of four months duration, with a treatment phase of 8
      wk followed by 8 wk of no treatment. RESULTS: Post intervention, at 8 wk and at
      16 wk, the hemoglobin change in the nutrition education, supplementation,
      nutrition education with supplementation and control groups was 2.9, 1.9, 3.8 and
      -5.9%, respectively and 2.1, -1.9, 0 and -9.3%, respectively (as compared to
      initial values). There was no significant effect of any of the intervention at 8
      weeks. At 16 wk, there was significant positive effect of nutrition education
      group (p less than 0.05). The percent change in serum ferritin value at 16 wk in
      the nutrition education, supplementation, nutrition education with
      supplementation and control groups was 5.7, -2.3, -3.4 and -40%, respectively.
      Serum ferritin values were significantly higher for the nutrition education group
      (p < 0.001) as compared to the control. At 16 wk, the nutrition education group
      mothers showed significantly higher nutrition knowledge and the dietary iron
      intake of children was significantly higher than their control group counterparts
      (p < 0.0001). CONCLUSION: The study suggests that nutrition education did have a
      positive effect on the iron status possibly by improving the dietary iron intake.

PMID- 14722365
TI  - Determinants of childhood mortality and morbidity in urban slums in India.
AB  - The large and continuous increase in India's urban population and the concomitant
      growth of the population residing in slums has resulted in overstraining of
      infrastructure and deterioration in public health. The link between urbanization,
      a degraded environment, inaccessibility to healthcare and a deteriorating quality
      of life is significant and particularly evident in the sharp inequities in IMR if
      one looks at urban specific studies. It is hence, germane to address the
      appalling inequalities in the distribution and access to basic amenities and
      health services with a focus on enhanced service coverage, improved sanitation
      and water supplies and mobilization of community action for effectively
      mitigating the childhood death and disease burden in urban slums.

PMID- 14722366
TI  - Urban slum-specific issues in neonatal survival.
AB  - Urbanization is rapidly spreading throughout the developing world. An urban slum
      poses special health problems due to poverty, overcrowding, unhygienic
      surroundings and lack of an organized health Infrastructure. The primary causes
      of neonatal mortality are sepsis, perinatal asphyxia and prematurity. Home
      deliveries, late recognition of neonatal illness, delay in seeking medical help
      and inappropriate treatment contribute to neonatal mortality. Measures to reduce
      neonatal mortality in urban slums should focus on health education, improvement
      of antenatal practices, institutional deliveries, and ensuring quality perinatal
      care. Success of a comprehensive health strategy would require planned health
      infrastructure, strengthening and unification of existing health care program and
      facilities; forming a system of referral and developing a program with active
      participation of the community.

PMID- 14722367
TI  - Improving drug safety monitoring.
AB  - Drug safety monitoring is important in children. Young age, polypharmacy,
      prolonged hospitaliza-tion, being critically ill and use of unlicensed and off
      label drugs have been identified as risk factors which predispose a child to
      experience an adverse drug reaction. In our country, the HIV/AIDS epidemic,
      setting up of intensive care units, increasing availability of imaging studies,
      and the introduction of several new drugs and vaccines have accentuated the need
      for improving drug safety monitoring in children. To achieve this aim,
      establishing in-hospital computerized event monitoring program in major hospitals
      and an effective national post- marketing drug surveillance network are the need
      of the hour.

PMID- 14722368
TI  - Acute iron poisoning: clinical picture, intensive care needs and outcome.
AB  - In this retrospective study, we examined the prevalence of acute iron poisoning
      among children attending Pediatric Emergency service of a teaching hospital, and
      studied their clinical profile, treatment and outcome to define intensive care
      needs. During the 5 years' study period of 27125 patient visits to Pediatric
      Emergency, 337 (1.2%) were for accidental poisoning. Of these 21(7%) patients had
      iron poisoning; 18 were transferred to PICU. Three patients were asymptomatic,
      others had vomiting (n =15, 83%), diarrhoea (n =13, 72%), malena (n = 8, 44%),
      and hemetemesis (n=6, 33%) generally within 6 hours of ingestion. Nine progressed
      to shock and/or impaired consciousness; two had acute liver failure. Dose of
      ingested iron and clinical signs were most useful guide to iron toxicity and
      management decisions; serum iron did not help. Gastric lavage yielded fragments
      of iron tablets in 10 patients. On desferrioxamine infusion Vin-rose colour urine
      was not seen in 31% even in presence of high serum iron. Shock responded to
      normal saline (33 +/- 15 mL/kg) and dopamine (10 +/- 4 microg/kg/min) within 4-24
      hours in 7 of 9 patients. Presence of shock or acute liver failure with
      coagulopathy and/or severe acidosis predicted all the four deaths.
      Desferrioxamine infusion and supportive care of shock was the mainstay.

PMID- 14722369
TI  - CSF Glucose Concentrations in Infants with Febrile Convulsions and the Possible
      Effect of Acetaminophen.
AB  - The present study was done to explore the relationship between the cerebrospinal
      fluid (CSF) glucose concentration, body temperature, seizure duration, and
      acetaminophen administration. Retrospective record review of 117 consecutive
      febrile convulsive infants aging 3 to 18 months admitted to Bahrami Children
      Hospital were studied. There was a positive correlation between CSF glucose level
      and body temperature in those who had not taken acetaminophen before admission (r
      = 0.515, n = 83). CSF glucose levels were significantly higher (P = 0.014) in
      febrile children (75.33 mg/dL, n =70) as compared with afebrile children (66.16
      mg/dL, n = 13). In those administered acetaminophen there was a negative
      correlation between the CSF glucose level and body temperature (r = - 0.389, P =
      0.023, n = 34). CSF glucose concentration was not significantly different (P =
      0.076) in those who had taken acetaminophen than those who had not taken. Type of
      febrile seizure, fever, convulsion duration and multiplicity were not
      significantly correlated with CSF glucose concentration.

PMID- 14722370
TI  - Efficacy of twice weekly iron supplementation in anemic adolescent girls.
AB  - Two hundred and forty four girls with different hemoglobin levels were selected,
      of which forty-one were non-anemic. The rest were graded as mildly, moderately or
      severely anemic and supplemented with 60 mg of iron daily or twice weekly for
      twelve weeks. There was no significant difference in the increase in hemoglobin
      levels between daily and twice weekly-supplemented subjects at the end of the
      study. Unpleasant side effects of supplementation were experienced by 57.8% of
      the daily supplemented subjects as against 5.9% of twice weekly-supplemented
      ones. Twice weekly supplementation could be recommended for overcoming anemia in
      adolescent girls.

PMID- 14722371
TI  - Acute myeloid leukemia presenting simultaneously in two siblings.
AB  - The rare occurrence of acute myeloid leukemia simultaneously in two siblings, 3
      year male and 1-year female, in the absence of any known predisposing condition
      is reported. We speculate that an initial in-utero genetic alteration followed by
      subsequent environmental exposure to some unknown toxin may have resulted in
      leukemogenesis.

PMID- 14722372
TI  - Growing skull fractures.
AB  - Growing skull fractures or craniocerebral erosions are rare sequel to cranial
      fractures where progressively growing cranial defects follow lacerations
      involving the duramater. Their usual site is the parietal region. They present as
      a cystic, non-tender swelling with an underlying palpable bony defect. One such
      case is reported.

PMID- 14722373
TI  - Papillon-Lefevre syndrome.
AB  - Papillon- Lefevre syndrome (PLS) is a rare autosomal recessive disorder of
      keratinization characterized by palmoplantar hyperkeratosis, periodontopathy and
      precocious loss of dentition. The exact pathomechanism of these clinical events
      mainly remains speculative. This paper describes two cases of PLS with classic
      clinical features and briefly review the relevant literature.

PMID- 14722374
TI  - Congenital Long QT Syndrome presenting as epilepsy.
AB  - Epilepsy can sometimes be mimicked in children by other organic conditions. We
      present a 11 year old boy with the congenital long QT syndrome who had recurrent
      "seizures" for five years which had been treated as epilepsy.

PMID- 14722375
TI  - Macroglossia.

PMID- 14722376
TI  - Persistant unconjugated hyperbilirubinemia in an infant with crigler-najjar
      syndrome type I.

PMID- 14722377
TI  - Improving oxygenation in preterm neonates with respiratory distress.

PMID- 14722378
TI  - Distal asymmetric spinal muscular atrophy involving upper limbs.

PMID- 14722380
TI  - Resuscitation of asphyxiated newborns(1).

PMID- 14722381
TI  - Resuscitation of asphyxiated newborns(2).

PMID- 14722382
TI  - Resuscitation of asphyxiated newborns(3).

PMID- 14722388
TI  - Delayed gastric emptying in gastroesophageal reflux disease: reassessment with
      new methods and symptomatic correlations.
AB  - BACKGROUND: Previous studies have shown that patients with gastroesophageal
      reflux disease (GERD) have slower rates of gastric emptying than control
      subjects, but the prevalence has differed because of variations in methodology.
      The recent establishment of international control values for scintigraphic
      gastric emptying assessment makes standardization of this technique possible. It
      would also be useful to determine whether specific gastrointestinal symptoms
      predicted delayed gastric emptying in GERD. METHODS: Forty-nine patients (mean
      age, 42.9 years; range, 24-65 years; 35 women, 14 men) who were diagnosed with
      GERD in the previous 12 months were given a standardized 280-kcal 99Tc-labeled
      low fat meal (egg beater). Percentage of intragastric residual content was
      recorded at baseline and at hourly intervals for 240 minutes by scintigraphy.
      Patients were also asked about the presence of dyspepsia (bloating, postprandial
      discomfort or belching, or early satiety), dysphagia, or regurgitation. RESULTS:
      Sixteen patients (33%) had intragastric residual contents greater than the 95th
      percentile (>40%) at 120 minutes, and 13 (26%) had abnormal results at 240
      minutes (>6%). Dyspepsia was present in all patients. Regurgitation and dysphagia
      were common (present in approximately 80% and 40% of patients, respectively) and
      the prevalence of these symptoms did not differ between patients with normal
      versus delayed gastric emptying. CONCLUSIONS: Using standardized techniques: 1)
      delayed gastric emptying is common in patients presenting with GERD at both 120
      and 240 minutes after ingestion of a solid meal and 2) symptoms alone are not a
      useful predictor of this pathophysiology. Awareness of this subgroup of patients
      can be important in treatment strategies and long-term therapy.

PMID- 14722389
TI  - Intradialytic administration of amphotericin B: clinical observations on efficacy
      and safety.
AB  - BACKGROUND: Amphotericin B is used commonly to treat fungal infections.
      Unfortunately, little information exists regarding the use of intravenous
      amphotericin B in patients with end-stage renal disease (ESRD). METHODS: We
      retrospectively reviewed the clinical course of patients receiving amphotericin B
      during hemodialysis (HD). Twenty-five episodes of systemic fungal infection
      occurring in 24 patients with ESRD treated with parenteral amphotericin B
      administered during HD were noted. Patients received a maintenance dose of 0.5 to
      1.0 mg/kg amphotericin B intravenously thrice weekly during HD sessions. Twenty
      three patients received either 500 or 1000 mg of amphotericin B, whereas 1
      patient with AIDS received a total of 6,500 mg. RESULTS: Intradialytic
      hypotension developed in 27.7% of HD sessions during treatment with amphotericin
      B compared with 28.8% of 20 HD sessions evaluated before initiation of
      amphotericin B therapy. Four patients exhibited a temperature rise greater than
      38.8 degrees C during drug infusion (1 episode per patient). Increases in heart
      rate and ventricular ectopy were rare. Serum potassium concentrations as well as
      Kt/V and urea reduction ratio did not change significantly. All patients (except
      the patient with AIDS) resolved their respective fungal infections. CONCLUSIONS:
      Intradialytic administration of amphotericin B was generally well tolerated. Our
      observations suggest that amphotericin B is effective and safe for outpatient
      intradialytic therapy when administered according to protocol.

PMID- 14722390
TI  - The effects of exercise on markers of lipid peroxidation in renal dialysis
      patients compared with control subjects.
AB  - PURPOSE: The purpose of this study was to compare the susceptibility to exercise
      induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and
      non-CMD control subjects. DESIGN: Cross-sectional comparison of exercise-induced
      changes in breath ethane and pentane flux between patients on CMD (group A) and
      an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched
      comparison group (group B). Breath ethane and pentane were measured at rest
      before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic
      acidosis threshold (Vo2lat), and 5 minutes after CPX. RESULTS: Group comparisons
      of clinical characteristics reveal that the groups were similar in terms of age,
      ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of
      aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors.
      All subjects successfully completed the CPX protocol achieving Vo2lat. There were
      significant differences in breath ethane flux between group A and B subjects,
      with greater pre-exercise, Vo2lat, and postexercise ethane levels in group A
      compared with group B subjects, and significant group differences, with lower
      breath ethane/pentane flux ratios at rest, Vo2lat, and recovery with lower ratios
      in group B than group A subjects. DISCUSSION/CONCLUSIONS: This study shows that
      patients on CMD have greater lipid peroxidation compared with control subjects at
      rest and during and after physical exercise. In addition, compared with control
      subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty
      acids at rest and during physical exercise and recovery. The lipid peroxidation
      profile may result in an unfavorable endoperoxide shift and should be evaluated
      further, along with modalities to reduce oxidative stress among patients on CMD.

PMID- 14722391
TI  - Hypercalcemia in patients with disseminated coccidioidomycosis.
AB  - OBJECTIVE: Granulomatous disorders may be associated with hypercalcemia. In
      sarcoidosis, the pathogenesis of hypercalcemia has been clarified, whereas in
      other granulomatous disorders, such as coccidioidomycosis, the mechanism is
      unclear. We present 13 patients with coccidioidomycosis and hypercalcemia to
      illustrate the clinical course and the mechanism of hypercalcemia. METHODS: We
      retrospectively reviewed all patients admitted to Kern Medical Center, a 270-bed
      public hospital, from 1990 through 1997 with coccidioidomycosis and a serum
      calcium level of greater than 10.5 mg/dL on at least 3 occasions. In addition, no
      other causes for hypercalcemia were identified. RESULTS: The mean highest serum
      calcium level was 12.7 +/- 1.8 mg/dL. All patients had disseminated disease. Six
      patients were nonambulatory and 4 had bone involvement. Of the 9 patients in whom
      parathyroid hormone was measured, it was normal in 6 and suppressed in 3. Of the
      9 patients in whom 25-hydroxyvitamin D was measured, it was normal in 6,
      suppressed in 2, and elevated in 1. Of the 7 patients in whom 1,25
      dihydroxyvitamin D was measured, it was normal in 3 and suppressed in 4. Urinary
      calcium was elevated in 2 patients, both of whom were ambulatory. Nonambulatory
      patients had significantly higher serum calcium levels (14.3 +/- 1.0 mg/dL) than
      ambulatory patients (11.3 +/- 0.46 mg/dL) (P<0.001). CONCLUSIONS: The mechanism
      of hypercalcemia in coccidioidomycosis is unrelated to increased production of
      1,25-dihydroxyvitamin D. Nonambulatory status is associated with higher mean
      serum calcium.

PMID- 14722392
TI  - Can prescription refill feedback to physicians improve patient adherence?
AB  - BACKGROUND: Although adherence to long-term drug therapy is an important issue,
      the means to facilitate its assessment and improvement in clinical practice
      remain a challenge. OBJECTIVE: To evaluate the impact of prescription refill
      feedback and adherence education provided to primary care physicians. METHODS: We
      provided 83 resident and attending physicians at a university-based general
      internal medicine practice with refill adherence reports on each of 340 diabetic
      patients. An educational session on adherence assessment and improvement
      techniques was held, and all physicians received a written outline on this topic.
      Physician attitude toward the intervention and 6-month change in refill adherence
      (doses filled/doses prescribed) of their patient panels were assessed. A
      nonrandomized comparison group of patients receiving hypertension medications for
      whom the physicians did not receive feedback was also evaluated. RESULTS: The
      overall improvement in mean refill adherence was not significant (83.9% vs 86.0%,
      P=0.18). The educational session was attended by 53% of the physicians. The
      patient refill adherence of physicians attending the educational session improved
      by 5.0% (P<0.0009) with no significant change among patients of physicians not
      attending the session. There was no adherence change among patients for whom
      physicians did not receive refill feedback data, regardless of educational
      session attendance. CONCLUSIONS: Patients of physicians that received refill
      feedback and attended an educational session improved their refill adherence.
      After replication of these results in a randomized trial, broad implementation of
      this approach could have substantial impact from a public health perspective,
      given the ubiquity of prescription claims data.

PMID- 14722393
TI  - Advance care planning: does patient gender make a difference?
AB  - BACKGROUND: Although it has received little study, gender may significantly
      affect patients' attitudes about advance care planning. METHODS: We asked 26
      Mexican American (14 male, 12 female), 18 European American (7 male, 11 female),
      and 14 African American (7 male, 7 female) inpatients for their attitudes about
      advance care planning and dying. Coders of different ethnicities and genders
      performed independent, blinded content analyses of responses. RESULTS: The
      interviews identified 40 themes. Five, including "Advance directives (ADs)
      improve the chances a patient's wishes will be followed," characterized both
      genders of all 3 ethnic groups. Although no individual themes distinguished the
      genders across ethnic groups, 3 meta-themes--or clusters of related themes--did.
      Men's end-of-life wishes addressed functional outcome alone, but women's wishes
      addressed other factors, too. Men felt disempowered by the health system, but
      women felt empowered. Men feared harm from the system, but women anticipated
      benefit. Each ethnic group expressed these gender differences uniquely. For
      example, most Mexican American men preferred death to disability, believed "the
      health care system controls treatment," and wanted no "futile" life support. In
      contrast, most Mexican American women expressed wishes only about care other than
      life support (especially about when and where they wanted to die), believed ADs
      "help staff know...(such) wishes," and trusted the system to "honor (written)
      ADs." CONCLUSION: Core cultural attitudes observed in both genders of 3 ethnic
      groups may extend to all Americans. Although core attitudes may support advance
      care planning for many Americans, health professionals should consider tailoring
      it to other, ethnic- and gender-specific attitudes.

PMID- 14722394
TI  - Medical errors and the trainee: ethical concerns.
AB  - How medical errors are handled by individual physicians and hospital systems is a
      topic of considerable interest. In teaching hospitals, medical students and house
      officers often observe and commit mistakes. Commission of a mistake is associated
      with serious emotional turmoil and uncertainty among trainees as well as
      experienced physicians. Although disclosure is the ethical standard, the
      consequences of disclosure are feared by many. This article focuses on the issues
      that surround medical errors as they pertain to medical students and residents.
      It is important that this group of future physicians has appropriate training,
      mentoring, and support when dealing with errors.

PMID- 14722395
TI  - Hypopituitarism and diabetes insipidus with localized hypertrophic
      pachymeningitis (Tolosa-Hunt syndrome) associated with Hashimoto thyroiditis.
AB  - We report a 69-year-old woman with intracranial pachymeningitis showing
      hypopituitarism, diabetes insipidus, and Tolosa-Hunt syndrome associated with
      Hashimoto thyroiditis confirmed by autopsy. A large tumorous lesion of the
      hypothalamo-pituitary gland was revealed on magnetic resonance imaging, after the
      patient complained of gait and visual field disturbance. These symptoms subsided
      after thyroid hormone supplementation. Hypopituitarism and diabetes insipidus
      were diagnosed after cessation of the treatment by the patient herself. Multiple
      cranial nerve palsies and orbito-frontalgia appeared. Methylprednisolone pulse
      therapy improved the symptoms, but they recurred when the dose of glucocorticoid
      was decreased. The patient died of brain thrombosis. Autopsy revealed typical
      findings of Hashimoto thyroiditis and intracranial pachymeningitis involving the
      cranial base and pituitary gland. The high titer of rheumatoid factor and
      Hashimoto thyroiditis in this patient suggest an immunological role in the
      pathogenesis of pachymeningitis.

PMID- 14722396
TI  - Sudden painless unilateral vision loss caused by branch retinal artery occlusion:
      implications for the primary care physician.
AB  - We report a case of sudden onset visual loss caused by branch retinal artery
      occlusion. Systematic search for the cause of branch retinal artery occlusion
      revealed Factor V Leiden mutation and antiphospholipid antibody syndrome as the
      cause. Implications for diagnosis and management are discussed.

PMID- 14722397
TI  - Perinephric abscess from insulin syringe reuse.
AB  - Perinephric abscess is a rare and often missed diagnosis. Diabetes mellitus and
      injection drug use are often considered among the predisposing factors for
      perinephric abscess. Diabetic patients are taught to discard insulin syringes
      after a single use. Described here is a patient who developed perinephric abscess
      from contaminated insulin syringes. Physicians are often unaware of the high
      prevalence of disposable insulin syringe reuse in the community.

PMID- 14722398
TI  - Successful treatment of Good syndrome with cytomegalovirus duodenoenteritis using
      a combination of ganciclovir and immunoglobulin with high anti-cytomegalovirus
      antibody titer.
AB  - We describe the case of a 64-year-old woman with Good syndrome who presented with
      watery diarrhea and abdominal distention caused by cytomegalovirus (CMV)
      duodenoenteritis. Thymoma and hypogammaglobulinemia were first identified when
      the patient was 58 years old. She had repeatedly complained of symptoms even
      after thymectomy. Abdominal radiography revealed multiple air-fluid levels, and
      computed tomography revealed ascites and dilation of the small intestine.
      Immunofluorescent staining of specimens obtained by duodenal mucosal biopsy
      revealed intracellular inclusion bodies of CMV, although serum CMV pp65
      antigenemia assays yielded negative results. CMV infection of the small intestine
      caused mucosal edema resulting in malabsorption. The patient was treated using
      ganciclovir and an immunoglobulin preparation with a high titer of antibodies
      against CMV (CMV-Ig), and subsequently made a rapid recovery from abdominal
      symptoms. When patients with Good syndrome complain of abdominal symptoms,
      particularly chronic diarrhea, a diagnosis of CMV gastroenteritis should not be
      excluded, even if negative results are obtained for CMV pp65 antigenemia assays.
      Combination therapy of ganciclovir and CMV-Ig seems useful for patients with CMV
      gastroenteritis.

PMID- 14722399
TI  - Gatifloxacin and prolonged QT interval.
AB  - We report the case of a 54-year-old woman who, while being treated for acute
      sinusitis with gatifloxacin, presented with syncope and was found to have a
      markedly prolonged QT interval. After stopping gatifloxacin, the QT interval
      normalized. We speculate that her episode of syncope was caused by a ventricular
      arrhythmia that resulted from an increased QT interval.

PMID- 14722400
TI  - A prospective, randomized controlled clinical trial of anterior lumbar interbody
      fusion using a titanium cylindrical threaded fusion device.
AB  - STUDY DESIGN: A prospective, randomized, controlled clinical trial comparing a
      cylindrical threaded titanium cage to a femoral ring allograft control for
      anterior lumbar interbody fusion. OBJECTIVE: To compare these two implants with
      regard to arthrodesis. Secondary outcome measures included pain relief,
      neurological status, and general health status. SUMMARY OF BACKGROUND DATA:
      Anterior lumbar interbody fusion is a well-accepted procedure using trapezoidal
      femoral ring allografts or cylindrical titanium cages. Clinical and biomechanical
      studies evaluating these two distinct constructs are numerous; however, no
      prospective, randomized study comparing them has been done. METHODS: A
      multicenter trial of 140 patients: 78 were randomized to the cylindrical threaded
      titanium cage device treatment arm and 62 patients randomized into the control
      group. All had autogenous iliac crest bone graft packed into the device. All
      patients had a single-level stand-alone anterior lumbar interbody fusion at
      either the L4-L5 or L5-S1 interspace for symptomatic degenerative disc disease.
      Radiographic fusion data were collected as well as multiple types of outcome
      data, including pain/disability scores, neurologic status, and overall health.
      RESULTS: At 12 months, 97% of the cylindrical threaded titanium cage device group
      and 40% of the control group demonstrated radiographic fusion. At 24 months, 97%
      of the cylindrical threaded titanium cage group and 52% of the control group
      showed radiographic fusion. These fusion rate differences are statistically
      significant (P < 0.001). The Oswestry and neurologic scores were not
      significantly different between groups. DISCUSSION: This is the first
      prospective, randomized, multicenter clinical trial that compares fusion cage
      results to control data. CONCLUSION: Cylindrical threaded titanium cages have a
      higher fusion rate, comparable improvements in clinical outcome (Oswestry, Low
      Back Pain Questionnaire, SF-36), and fewer secondary supplemental fixation
      procedures compared to the femoral ring allograft control.

PMID- 14722402
TI  - Spinal flexibility increase after chymopapain injection is dose dependent: a
      possible alternative to anterior release in scoliosis.
AB  - STUDY DESIGN: Experimental animal study. OBJECTIVES: To investigate whether the
      increase in spinal flexibility after chymopapain injection is dose dependent and
      determine the "optimal" dosage of chymopapain to increase spinal flexibility in a
      rabbit model. SUMMARY OF BACKGROUND DATA: Spinal instability after chymopapain
      injection may result in severe back pain. However, this undesired mechanical
      effect in treating disc herniation may provide a safe minimally invasive approach
      for anterior spinal release in scoliosis correction. METHODS: A total of 138
      lumbar intervertebral discs from 46 New Zealand white rabbits were randomly
      injected with chymopapain at 6.25, 12.5, 25, 50, 75, and 100 picokatals
      (pKats)/0.05 mL/disc. The rabbits were killed 1 week after the injection, and the
      lateral bending stiffness of the spinal segments without posterior elements was
      determined. RESULTS: The lateral bending spinal stiffness showed no significant
      change after injection of 6.25 and 12.5 pKats/0.05 mL/disc but reduced
      significantly following chymopapain injection of 25, 50, 75, and 100 pKats (all P
      < 0.05 by post hoc least significant difference tests). While the lateral bending
      stiffness was lowest at the 100-pKats dose, there were no significant differences
      between the four higher dosages. CONCLUSION: The reduction in the lateral bending
      spinal stiffness after chymopapain injection is dose dependent, and an optimal
      dosage for spinal release existed; doses greater than the optimal dosage did not
      result in further significant decrease in lateral bending spinal stiffness.

PMID- 14722403
TI  - Tensile transmission across the lumbar fasciae in unembalmed cadavers: effects of
      tension to various muscular attachments.
AB  - STUDY DESIGN: Traction was applied to muscles attaching to the posterior and
      middle layers of lumbar fascia (PLF, MLF). Effects on fasciae were determined via
      tensile force measures and movement of markers. OBJECTIVES: To document tensile
      transmission to the PLF and MLF when traction was applied to latissimus dorsi
      (LD), gluteus maximus (GM), external and internal oblique (EO, IO), and
      transversus abdominis (TrA) in unembalmed cadavers. SUMMARY OF BACKGROUND DATA: A
      previous study on embalmed cadavers applied traction to muscle attachments while
      monitoring fascial movement but did not test TrA or the MLF. METHODS: The PLF and
      MLF were dissected then marked on eight unembalmed cadavers. A strain gauge was
      inserted through fascia at L3; 10N traction was applied to each muscle attachment
      while photographs and tension measures were taken. Movement of fascial markers
      was detected photographically. Fascial widths were also measured. RESULTS:
      Tension was clearly transmitted to fascial vertebral attachments. Tensile forces
      and fascial areas affected were highest for traction on LD and TrA in the PLF and
      for TrA in the MLF. Movement of PLF markers from tension on LD and TrA occurred
      bilaterally between T12 and S1. Effects from other muscles were variably
      bilateral, with those from GM and IO occurring below L3 and those from EO
      occurring above L3. Tensile forces were relatively high in the MLF and its width
      was less than half that of the PLF. CONCLUSIONS: Low levels of tension are
      effectively transmitted between TrA and the MLF or PLF. Via them, TrA may
      influence intersegmental movement.

PMID- 14722404
TI  - Morphometric comparison of the pedicle rib unit to pedicles in the thoracic
      spine.
AB  - STUDY DESIGN: A radiographic study of the pedicle rib unit morphology as compared
      with measurements of the pedicle in cadaveric thoracic spines. OBJECTIVE: To
      evaluate the morphology of pedicle rib units in the thoracic spine in normal
      thoracic human spines, with particular attention to T4-T9, and to compare the
      dimensions of the pedicle rib unit with corresponding dimensions of the adjacent
      pedicles. SUMMARY OF BACKGROUND DATA: Despite the clinical successes reported
      with thoracic pedicle screw-rod constructs, controversy exists as to the safety
      of this technique in pedicles that are anatomically too small for transpedicular
      fixation. An alternative method of extrapedicular screw fixation within the
      pedicle rib unit was evaluated in a previous study and found to be anatomically
      feasible. Although the morphology of the pedicle rib unit was described in two
      previous studies, the measurements were obtained in scoliotic spines. Therefore,
      no study has sought to define the transverse dimension and chord length of the
      pedicle rib unit, and compare it with the corresponding pedicle dimensions.
      MATERIAL AND METHODS: Six fresh unfixed adult cadavers were obtained randomly. No
      history of spine disease was noted, and cause of death was unrelated to spinal
      disorder or trauma. The mean age was 84, with a range of 76 to 90. There were two
      females and four males. Computerized tomographic (CT) images of the thoracic
      spine were obtained. For cadavers in which the gantry resulted in oblique axial
      sections, reformatting was performed for more accurate measurements. Measurements
      of the transverse diameter and chord length of the pedicle rib unit were obtained
      and compared with measurements of the transverse pedicle width and chord length.
      RESULTS: The transverse width and chord length of the pedicle rib unit were
      significantly larger than corresponding pedicle measurements at all levels, a
      consistent finding when comparing the mean of all levels, the mean of T4-T9, and
      the mean of each individual level T4-T7. CONCLUSION: This study confirms the
      marked difference in size of the pedicle rib unit as compared with the pediclein
      both transverse width and chord length. This allows for a space that accommodates
      much larger major screw diameters, longer screw lengths, and because of the
      nature of screw placement, a greater screw convergence. Thus, there is anatomic
      potential for extrapedicular vertebral body fixation in the thoracic spine.
      However, care must be taken in placement of screws following precisely our
      previously described method of extrapedicular screw insertion. Penetration of
      surrounding structures, most notably the aorta on the left, is a potential risk
      when deviating from the method. Biomechanical evaluations are presently being
      conducted to evaluate the use of extrapedicular thoracic screw fixation.

PMID- 14722405
TI  - The effects from lumbar nerve root transection in rats on spinal somatosensory
      and motor-evoked potentials.
AB  - STUDY DESIGN: Spinal somatosensory-evoked potentials (SSEPs), elicited by mixed
      nerve and dermatomal stimulation, and compound evoked muscle potentials (CMAPs),
      elicited by lower thoracic interspinous space stimulation, were recorded in rats
      that underwent single nerve root transection. OBJECTIVES: To investigate and
      compare the effects of single nerve root transection using various
      electrophysiological models and to define a monitoring strategy that can easily
      and accurately predict compromise caused by a single lumbosacral nerve root
      injury. SUMMARY OF BACKGROUND DATA: Neuromonitoring is an important and effective
      preventive measure against neurologic complications during spinal surgery, but
      monitoring the lumbosacral nerve roots is not well established. METHODS: Rats
      received (Group I) a sham operation or had the (Group II) left L4, (Group III)
      L5, or (Group IV) L6 nerve root transected. SSEP were recorded at the
      thoracolumbar junction following stimulation of the sciatic nerve (M-SSEP) and
      the L5 dermatome (D-SSEP). CMAP was recorded at the intrinsic muscles of the foot
      by electrical stimulation in the lower thoracic spinal cord. Potentials recorded
      before and after a single nerve root transection were compared and correlated
      with clinical status by walking-track analysis 1 week later. RESULTS: Relative
      amplitudes in Group II were 54.1% (M-SSEP), 84.6% (D-SSEP), and 85.5% (CMAP);
      25.2% (M-SSEP), 66.5% (D-SSEP), and 85.8% (CMAP) in Group III; and 66.5% (M
      SSEP), 95.5% (D-SSEP), and 23.2% (CMAP) in Group IV. M-SSEP is sensitive but not
      specific to single nerve root injury. D-SSEP and CMAP are less sensitive but more
      specific. CONCLUSIONS: Injury to a single lumbosacral nerve root is diagnosed
      more easily with M-SSEP. With D-SSEP and CMAP, it was possible to differentiate
      the lesioned nerve root by stimulating the primary dermatome or recording from
      the innervated muscle. M-SSEP is an easy-sampling and appropriate tool for
      screening nerve root injury; its poor specificity may be overcome by using D-SSEP
      and CMAP in addition. Optimal monitoring of the lumbosacral nerve roots during
      lumbar spinal surgery requires the administration of M-SSEP, D-SSEP, and CMAP to
      provide independent verification of lumbosacral nerve root integrity and to allow
      detection of the occasional injuries that selectively affect either the sensory
      or motor system.

PMID- 14722406
TI  - In vivo growth factor treatment of degenerated intervertebral discs.
AB  - STUDY DESIGN: An in vivo model was used to investigate the response of
      degenerated discs to various exogenous growth factors. OBJECTIVES: To study
      growth factor-induced alterations of the spatial and temporal patterns of disc
      cellularity and matrix gene expression. SUMMARY OF BACKGROUND DATA: Cell
      proliferation and proteoglycan synthesis have been stimulated by growth factors
      in normal disc cells, suggesting that growth factors may play a therapeutic role
      for degeneration. However, the response in situ in degenerated discs has not been
      characterized. METHODS: Degeneration was induced in murine caudal discs by static
      compression. Degenerated discs were given single or multiple injections of growth
      and differentiation factor-5, transforming growth factor-beta, insulin-like
      growth factor-1, basic fibroblast growth factor, or saline as control.
      Comparisons of disc morphology, anular cell density, proliferating cells, disc
      height, and aggrecan and type II collagen gene expression were made either 1 week
      or 4 weeks after treatment. RESULTS: In some growth and differentiation factor-5
      and transforming growth factor-beta treated discs, expansion of inner anular
      fibrochondrocyte populations into the nucleus was observed. The cells actively
      expressed aggrecan and type II collagen mRNA. A lesser effect was observed for
      insulin-like growth factor-1 and little or no effect for basic fibroblast growth
      factor. Differences in cell density and proliferating cells were not significant
      between treatments but suggested a trend of increased cellularity and
      proliferation following growth factor treatment. A statistically significant
      increase in disc height 4 weeks after growth and differentiation factor-5
      treatment was measured. CONCLUSIONS: Anular fibrochondrocytes in degenerated
      discs are responsive to some growth factors in vivo. The results have
      implications in the early intervention of disc degeneration to arrest or slow the
      degenerative process.

PMID- 14722407
TI  - Study of bacterial translocation from gut after paraplegia caused by spinal cord
      injury in rats.
AB  - STUDY DESIGN: Normal rats and paraplegic rats with and injured spinal cord were
      used to study bacterial translocation from gut. OBJECTIVE: To investigate whether
      bacterial translocation from gut occurs after spinal cord injury. SUMMARY OF
      BACKGROUND DATA: It has been demonstrated that trauma and operation can lead to
      gastrointestinal paralysis; disturbance of gastrointestinal motility following
      trauma may cause bacterial overgrowth in gastrointestinal tract and increase the
      incidence of bacterial translocation. However, bacterial translocation from gut
      after spinal cord injury has not been studied. METHODS: Under aseptic
      manipulation, samples of blood were collected for bacterial cultures and
      endotoxin determination. In the meantime, samples of mesenteric lymph node,
      spleen, and liver were collected for bacterial culture. The jejunum and ileum
      were observed by light and electron microscope. RESULTS: Endotoxemia and
      bacterial translocation appeared 24 hours and 48 hours correspondingly after
      spinal cord injury complicated with paraplegia. CONCLUSION: Bacterial
      translocation from gut would occur after spinal cord injury in rats, which
      indicated that antibiotics should be administered to paraplegic patients with
      spinal cord injury as soon as possible to prevent potential bacterial
      translocation.

PMID- 14722408
TI  - Instrumented fusion for degenerative spondylolisthesis: is it necessary?

PMID- 14722409
TI  - The argument for noninstrumented posterolateral fusion for patients with spinal
      stenosis and degenerative spondylolisthesis.

PMID- 14722410
TI  - The argument for instrumented decompressive posterolateral fusion for patients
      with degenerative spondylolisthesis and spinal stenosis.

PMID- 14722411
TI  - A retrospective radiographic analysis of subaxial sagittal alignment after
      posterior C1-C2 fusion.
AB  - STUDY DESIGN: Subaxial sagittal alignment following atlantoaxial (A-A) posterior
      fusion was investigated retrospectively in patients with A-A subluxation.
      OBJECTIVES: To evaluate the association between A-A fusion angle and
      postoperative subaxial sagittal alignment and to determine the optimal fusion
      angle for preservation of physiologic subaxial alignment. SUMMARY OF BACKGROUND
      DATA: A-A posterior fusion has been used for patients with A-A instability and
      provided satisfactory clinical results. However, there are patients showing
      unexpected development of subaxial kyphosis after surgery. The reasons for
      subaxial kyphosis after A-A fusion remain unclear. METHODS: Seventy-six patients
      with A-A subluxation who underwent several types of posterior A-A fusion were
      involved. There were 46 women and 30 men. The causes of A-A subluxation were
      rheumatoid arthritis in 47, trauma in 16, os odontoideum in 8, and unknown in 5.
      The methods of posterior fusion consisted of Magerl procedure with posterior
      wiring in 51, Brooks wiring in 18, and Halifax clamp in 7. Angles at C1-C2, C2
      C7, and C1-C7 in the neural position were measured before surgery and at the
      final follow-up to find out any association between postoperative C2-C7 angle and
      the other radiologic parameters. The association between O-C1 range of motion and
      C2-C7 angle was also investigated. RESULTS: The mean angles of C1-C2, C2-C7, and
      C1-C7 before surgery were 18.4 degrees, 14.5 degrees, and 32.9 degrees,
      respectively. Those at the final follow-up were 26.0 degrees, 5.5 degrees, and
      31.5 degrees, respectively. These results indicated that C1-C2 fixation in a
      hyperlordotic position led to a subaxial kyphosis after surgery. Statistics
      showed that there was a linear association between the C1-C2 lordotic fixation
      angle and the C2-C7 kyphotic angle. CONCLUSIONS: Surgical fixation of A-A joint
      in a hyperlordotic position will lead the lower cervical spine to a kyphotic
      sagittal alignment after surgery. To maintain the physiologic sagittal alignment
      of the subaxial cervical spine, C1-C2 should not be fixed in a hyperlordotic
      position.

PMID- 14722412
TI  - Characterization of acute whiplash-associated disorders.
AB  - STUDY DESIGN: An experimental study of motor and sensory function and
      psychological distress in subjects with acute whiplash injury. OBJECTIVES: To
      characterize acute whiplash injury in terms of motor and sensory systems
      dysfunction and psychological distress and to compare subjects with higher and
      lesser levels of pain and disability. SUMMARY OF BACKGROUND DATA: Motor system
      dysfunction, sensory hypersensitivity, and psychological distress are present in
      chronic whiplash associated disorders (WAD), but little is known of such factors
      in the acute stage of injury. As higher levels of pain and disability in acute
      WAD are accepted as signs of poor outcome, further characterization of this group
      from those with lesser symptoms is important. MATERIALS AND METHODS: Motor
      function (cervical range of movement [ROM], joint position error [JPE]; activity
      of the superficial neck flexors [EMG] during a test of cranio-cervical flexion),
      quantitative sensory testing (pressure, thermal pain thresholds, and responses to
      the brachial plexus provocation test), and psychological distress (GHQ-28, TAMPA,
      IES) were measured in 80 whiplash subjects (WAD II or III) within 1 month of
      injury, as were 20 control subjects. RESULTS: Three subgroups were identified in
      the cohort using cluster analysis based on the Neck Disability Index: those with
      mild, moderate, or severe pain and disability. All whiplash groups demonstrated
      decreased ROM and increased EMG compared with the controls (all P < 0.01). Only
      the moderate and severe groups demonstrated greater JPE and generalized
      hypersensitivity to all sensory tests (all P < 0.01). The three whiplash
      subgroups demonstrated evidence of psychological distress, although this was
      greater in the moderate and severe groups. Measures of psychological distress did
      not impact on between group differences in motor or sensory tests. CONCLUSIONS:
      Acute whiplash subjects with higher levels of pain and disability were
      distinguished by sensory hypersensitivity to a variety of stimuli, suggestive of
      central nervous system sensitization occurring soon after injury. These responses
      occurred independently of psychological distress. These findings may be important
      for the differential diagnosis of acute whiplash injury and could be one reason
      why those with higher initial pain and disability demonstrate a poorer outcome.

PMID- 14722413
TI  - Local autograft bone in the surgical management of adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: The study was performed to
      determine the efficacy of local autograft bone in idiopathic scoliosis surgery on
      patients who had had spinal fusion with a Cotrel Dubousset device between 1990
      and 1995. SUMMARY OF BACKGROUND DATA: Studies seemed to promote the used of
      autograft bone (iliac crest, ribs), allograft bone, or bone graft substitutes in
      adolescent idiopathic surgery. To the authors' knowledge, there have been no
      previous articles concerning in situ local auto graft bone in idiopathic
      scoliosis surgery in the literature. MATERIALS AND METHODS: Twenty five patients
      with idiopathic scoliosis, aged 11 to 18 years, were treated by posterior
      correction and arthrodesis using Cotrel-Dubousset instrumentation. Posterior
      spinal fusion was performed using only local bone grafts. The patients were
      reviewed with a mean postoperative observation time of 6 years (5-9). The results
      were assessed clinically and radiographically. RESULTS: Preoperative single
      curves averaged 56 degrees in the frontal plane with an average postoperative
      curve of 16 degrees. Preoperative double curves in the frontal plane averaged 55
      degrees in thoracic curves and 49 degrees in lumbar curves with an average
      postoperative curve of 18 degrees in thoracic and 13 degrees in lumbar. At the
      final follow-up, there was no losing in the correction. There was no
      pseudarthrosis clinically or radiographically. CONCLUSIONS: In adolescent
      idiopathic scoliosis surgery, local autograft bone allows to avoid the necessity
      of any over graft.

PMID- 14722414
TI  - Surgical correction of scoliosis by in situ contouring: a detorsion analysis.
AB  - STUDY DESIGN: A detorsion analysis of the scoliosis surgical correction by means
      of in situ contouring technique (ISC). OBJECTIVE: To describe the technique of
      ISC. To measure the vertebral and intervertebral axial rotation in thoracic and
      lumbar curves and their correction obtained by ISC. SUMMARY AND BACKGROUND DATA:
      The vertebral and intervertebral axial rotation allows to evaluate the severity
      of the curves. However, the intervertebral axial rotation is barely studied and
      the vertebral axial rotation is a controversial point of the surgical correction.
      METHODS: Twenty patients with thoracic and lumbar scoliosis were operated on with
      ISC. Vertebral axial rotation at the apex and the sum of intervertebral axial
      rotations all along the curve were computed before and after surgery from the
      three-dimensional stereoradiographic reconstruction of the spine and the pelvis.
      All the measurements were made in the standing position. RESULTS: Correction of
      the axial rotation was obtained at the apex of both thoracic and lumbar curves of
      idiopathic and degenerative scoliosis. The mean values of correction (in terms of
      axial rotation) were 8 degrees to 19 degrees (62%-67%). The percentage of
      correction of the sum of intervertebral axial rotations all along the curve,
      proposed as a "detorsion index" (preoperative - postoperative/preoperative), was
      found at 57% to 92%. No significant differences were found for the correction (in
      terms of axial rotation and detorsion) between idiopathic and degenerative
      curves. CONCLUSIONS: The axial rotation was measured in clinics on standing
      patients with scoliosis from three-dimensional stereoradiographic reconstruction
      and demonstrated a reliable detorsion obtained by ISC.

PMID- 14722415
TI  - Lumbosacral transitional vertebra: relation to disc degeneration and low back
      pain.
AB  - STUDY DESIGN: Cross-sectional magnetic-resonance imaging (MRI) study. OBJECTIVE
      To investigate the relation of the lumbosacral transitional vertebra to signs of
      disc degeneration in MRI and to low back pain (LBP). SUMMARY OF BACKGROUND DATA:
      An association between the transitional vertebra and herniation in the disc above
      has been found in patients with LBP, but knowledge of the relation to other
      degenerative disc changes detected in MRI and to LBP is lacking. METHODS: MR
      images of the lumbar spine of 138 middle-aged working men and 25 healthy young
      men were evaluated. The presence and type of lumbosacral transitional vertebra
      and of degenerative changes in intervertebral discs were evaluated. The history
      of low back symptoms was obtained with a questionnaire from the middle-aged men.
      RESULTS: The prevalence of transitional vertebra was 30%. Transitional vertebra
      was associated with an increased risk of degenerative changes in the disc above
      among the young men and with a decreased risk in the disc below among the middle
      aged men. Transitional vertebra, symmetric or asymmetric, was not associated with
      any type of LBP in the middle-aged men. CONCLUSIONS: Lumbosacral transitional
      vertebra increases the risk of early degeneration in the upper disc. This effect
      seems to be obscured by age-related changes in the middle age. The degenerative
      process is slowed down in the lower disc. For these effects, the presence of a
      transitional vertebra should be noticed when morphologic methods are used in
      research on lumbosacral spine. Transitional vertebra is not associated with any
      type of LBP.

PMID- 14722416
TI  - Correlation between pain, disability, and quality of life in patients with common
      low back pain.
AB  - STUDY DESIGN: Correlation among previously validated questionnaires. OBJECTIVES:
      To determine the correlation between pain, disability, and quality of life in
      patients with low back pain. SUMMARY OF BACKGROUND DATA: The Visual Analogue
      Scale (VAS), and the Roland-Morris (RMQ), Oswestry (OQ), and EuroQol (EQ)
      Questionnaires are validated instruments to assess pain, low back pain-related
      disability, and quality of life. METHODS: The study was done in the primary care
      setting, in Mallorca, with 195 patients who visited their physician for LBP.
      Individuals were given the VAS, RMQ, OQ, and EQ on their first visit and 14 days
      later. RESULTS: Median duration of pain when entering the study was 10 days
      (P25,P75: 3, 40). On day 1, simple correlation was r = 0.347 between VAS and RMQ,
      r = -0.422 between VAS and EQ, and r = -0.442 between RMQ and EQ. On day 15,
      simple correlation was r = 0.570 between VAS and RMQ, r = -0.672 between VAS and
      EQ, and r = -0.637 between RMQ and EQ. Multiple linear regression models showed
      that, on day 1, the VAS score explains 12% of the RMQ score and the VAS and RMQ
      scores explain 27% of the EQ score. On day 15, the VAS score explains 33% of the
      RMQ score, and the VAS and RMQ scores explain 58% of the EQ score. On day 1, a
      10% increase in VAS worsens disability by 3.3% and quality of life by 2.65%. On
      day 15, a 10% increase in VAS worsens disability by 4.99% and quality of life by
      3.80%. Prestudy duration of pain had no influence on any model. All these
      correlation coefficients and models are significant at the P < 0.001 level. The
      OQ had lower correlation values with the other three scales, and only two of them
      were significant. CONCLUSION: Clinically relevant improvements in pain may lead
      to almost unnoticeable changes in disability and quality of life. Therefore,
      these variables should be assessed separately when evaluating the effect of any
      form of treatment for low back pain. The influence of pain and disability on
      quality of life progresses while they last, and doubles in 14 days. In acute and
      subacute patients, this increase is not dependent on the previous duration of
      pain.

PMID- 14722417
TI  - Satisfaction with medical rehabilitation after spinal cord injury.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: To predict satisfaction with medical
      rehabilitation. SUMMARY OF BACKGROUND DATA: While spinal cord injury (SCI)
      patient satisfaction with life and community services has been investigated,
      satisfaction with medical rehabilitation has not. METHODS: Information submitted
      to the Uniform Data System for Medical Rehabilitation (1998-2001) by 134
      hospitals/rehabilitation facilities in the United States (n = 6,205 patients with
      SCI) was examined. Predictors were sociodemographic variables, Case Mix Groupings
      (CMG) (401-505, 5001), length of stay, rehospitalization, follow-up therapy, and
      health maintenance. Satisfaction was assessed at a mean of 92.2 days (SD 11.9
      days) postdischarge. Data were analyzed according to who reported the outcome
      (patient, n = 3,858 or family/other, n = 1,869). Statistical modeling was
      conducted using logistic regression. RESULTS: High overall satisfaction was
      reported (94%). Significant predictors for the patient report data were CMG and
      rehospitalization. Compared with CMG 5001 (short stay, <3 days), patients in CMGs
      401/2/3 and 501/2/3/4/5 had a 54% to 74% lower likelihood of being dissatisfied.
      Rehospitalized patients had a higher likelihood of dissatisfaction (odds ratio
      2.3, 95% confidence interval 1.7 to 3.2). Significant predictors for the
      family/other report data were CMG (compared to CMG 5001, CMGs 401/2, 403, and
      501/2 had a 70% lower likelihood of dissatisfaction), rehospitalization (odds
      ratio 1.7, 95% confidence interval 1.1-2.5), and marital status (married = 50%
      lower likelihood of dissatisfaction, 95% confidence interval 0.26-0.96).
      CONCLUSIONS: Satisfaction with medical rehabilitation services following SCI is
      related to functional abilities, rehospitalization, and marital status. Slightly
      different results were found for whether satisfaction was rated by the patient or
      family/other. The complex relationships among satisfaction, patient demographics,
      and functional status require continued examination.

PMID- 14722419
TI  - Feasibility study of a mini, bone-attached, robotic system for spinal operations:
      analysis and experiments.
AB  - STUDY DESIGN: In this investigation, a new concept of a miniature, bone-attached,
      medical robotic system for spinal operations is presented. As part of the design
      parameters of the robot, the forces and moments applied by the physician during
      insertion of Kirschner wires to soft tissues and drilling in hard tissues were
      examined. A theoretical model for the expected error of the robotic system due to
      the applied force has been derived and verified experimentally. The results of a
      clinical experiment that was carried out on a cadaver support the theoretical
      model derived and the miniature, bone-attached, robotic concept. OBJECTIVES: 1)
      Examining the concept of attaching a miniature robotic system to the spinous
      process of the operated vertebra. 2) Measuring the forces applied by the
      physician during insertion of Kirschner wires to soft tissues and drilling in
      hard tissues. 3) Evaluating the expected error of the robot due to mechanical and
      anatomic deflection caused by the forces applied by the physician during
      operation. 4) Testing and verifying the theoretical background by a clinical
      experiment. SUMMARY OF BACKGROUND DATA: Spinal operations are reported in the
      literature to have a relatively low success rate (70%-90%). This low success rate
      is affected by misunderstanding of the disease and its indications, resulting in
      bad selection of patients. From the technical point of view, the low success rate
      is greatly affected by the physician's lack of experience and the complexity of
      the spinal anatomy. The development of a miniature bone-attached robotic system
      for spinal operations could improve the success rate of spinal operations,
      introduce new percutaneous procedures, and shorten recovery and hospitalization
      time. Moreover, it will reduce the use of fluoroscopic exposure during operation;
      consequently, it will decrease considerably exposure to radiation during spinal
      operations. METHODS: Forces and moments applied by the physician during operation
      were measured by a 6-DOF miniature sensor. The measurements were taken during K
      wire insertion both to soft and to hard tissues of a sheep and a human cadaver. A
      theoretical model of the expected location error of a K-wire, inserted to
      selected vertebralanatomies by the robotic system, was derived and verified
      experimentally. RESULTS: The theoretical model agreed with the experimental
      results, meaning that the combination of the spinous process and the robotic
      structure is rigid enough to guide a K-wire accurately. The forces and moments
      were measured and analyzed, and the total expected error due to the forces and
      moments was calculated. The clinical experiments supported the theoretical model
      and proved the system's feasibility. CONCLUSIONS: The given results support the
      theoretical model developed. Moreover, a miniature robotic guiding system can be
      attached to the spinous process of a given vertebra. The deflection and system
      error resulting from the forces and moments acting during operation are within
      the allowable errors.

PMID- 14722420
TI  - Bilateral pedicle stress fractures in a female athlete: case report and review of
      the literature.
AB  - STUDY DESIGN: Clinical case report of bilateral stress fractures of the pedicle
      in a female athlete presenting with back pain. OBJECTIVES: To report this unusual
      case and surgical treatment and to review the relevant literature. SUMMARY OF
      BACKGROUND DATA: Low back pain is a frequent complaint in athletes, with the
      majority of cases being related to muscular or soft tissue etiology.
      Spondylolysis, or pars fracture, is the most common injury of the neural arch.
      Stress fracture of the pedicle is a much less common occurrence. Bilateral
      pedicle fractures in an otherwise healthy athlete has not been previously
      reported in the orthopedic literature. METHODS: A 19-year-old female athlete
      presented with low back pain limiting sports and daily activities. Radiographic
      workup revealed bilateral stress fractures of the pedicles of the L5 vertebra.
      Circumferential fusion of the L5-S1 segment was performed after failure of
      conservative treatment. Anterior interbody structural allograft and a vertical
      mesh cage were combined with instrumented posterolateral fusion using segmental
      pedicle screws and autogenous iliac crest bone graft. RESULTS: The patient
      achieved complete pain relief, solid fusion, and return to normal function.
      CONCLUSIONS: In this uncommon case of bilateral stress fractures of the pedicle,
      circumferential fusion assures full immobilization of the injured motion segment
      and assures a high probability of successful healing.

PMID- 14722421
TI  - Adjacent two-level lumbar discectomy: outcome and SF-36 functional assessment.
AB  - STUDY DESIGN: A retrospective outcomes study. OBJECTIVES: To examine the outcome
      following adjacent two-level lumbar discectomy using both surgeon-based
      evaluation criteria and validated patient-based quality of life instrument (SF
      36). SUMMARY OF BACKGROUND DATA: Lumbar discectomies have documented success
      rates between 49% and 98% for single-level procedures. However, no prior study
      has specifically examined the outcome following adjacent two-level lumbar
      discectomy in a large series of patients. METHODS: This study analyzed 55
      patients with a minimum 2-year follow-up. All patients underwent adjacent two
      level lumbar discectomy for radicular pain attributable to nerve root impingement
      at the corresponding levels. The patients were divided into two diagnostic groups
      based on their preoperative radiographic studies. Patients with two-level
      adjacent posterolateral lumbar disc herniations without concomitant osseous
      degenerative changes at the same levels constituted Group 1 (22 patients).
      Patients with associated osseous degenerative changes at the same levels made up
      Group 2 (33 patients). The patients' clinical outcome was assessed using the
      MacNab classification and SF-36 questionnaire. RESULTS: The average duration of
      follow-up was 41 months (range 24-96 months). The group consisted of 35 males and
      20 females with average age of 49 years (range 19-82 years). Excellent results
      were observed in 49%, good in 20%, fair in 15%, and poor in 16%. However,
      patients in Group 1 have 86% excellent/good results, whereas patients in Group 2
      have 57% excellent/good results. Overall, 15% of the patients required
      reoperation and subsequent spinal fusion. Analysis of the SF-36 scores revealed
      significant differences based on patient's diagnostic grouping as well. Patients
      in Group 1 have physical and mental summary scores comparable with age- and sex
      adjusted population norms and significantly higher than those in Group 2 (P <
      0.01). CONCLUSIONS: Two-level discectomy is an effective treatment with clinical
      outcome comparable with single-level discectomy. Patients with posterolateral
      disc herniations and definitive radiculopathy without osseous degenerative
      changes at the same levels have better clinical outcome and quality of life
      scores compared with those patients having concomitant degenerative arthritis at
      the same levels. Patients having two-level discectomy may be at increased risk of
      requiring subsequent lumbar fusion compared with those with single-level
      discectomy.

PMID- 14722422
TI  - Cervical disc herniation producing Brown-Sequard syndrome: case report.
AB  - BACKGROUND: Brown-Sequard syndrome is an incomplete spinal cord lesion
      characterized by a clinical picture reflecting hemisection of the spinal cord in
      the cervical or thoracic region. Brown-Sequard syndrome may be the result of
      penetrating injury to the spine, but many other etiologies have been described.
      In particular, cervical disc herniation has been rarely reported as a cause of
      this syndrome, and including the first article of Stookey in 1928, 9 only 22
      cases have been reported. METHODS: The case of a man with a large left paramedian
      C5-C6 disc herniation, with ipsilateral spinal cord compression, is reported. An
      area of left-sided spinal cord hyperintensity was also present on MRI, an
      expression of left hemicord damage. Microdiscectomy and anterior cervical fusion
      with carbon fiber cage containing a core of granulated coralline hydroxylapatite
      was performed. A complete motor deficit recovery and a marked sensitive deficit
      improvement was obtained. CONCLUSION: A critical review of the pertinent
      literature is proposed, and the neuroradiologic, therapeutic, and prognostic
      implications are discussed. Brown-Sequard syndrome produced by a cervical disc
      herniation is presumably often underdiagnosed, and early surgical intervention is
      always recommended.

PMID- 14722423
TI  - Chylous leakage after thoracolumbar fracture may cause paraplegia.
AB  - STUDY DESIGN: Retrospective case report. PURPOSE: This case demonstrates that
      paraplegia can develop due to chylous leakage into the spinal canal without
      obvious retroperitoneal or intrathoracic involvement. BACKGROUND INFORMATION:
      This clinical presentation of chylous leakage has not been reported previously.
      RESULTS A 61-year-old female with osteoporosis suffered a pathologic fracture of
      the vertebral bodies T12 and L1 and developed partial paraplegia two weeks later.
      Imaging showed expansive pooling of intraspinal fluid without intrathoracic or
      retroperitoneal involvement. A blood-tinged fluid was aspirated from dorsal.
      Repeated surgery by a posterior approach with drainage of the fluid did not
      improve the patient's condition, so she was finally transferred to our hospital.
      Under the suspected diagnosis of lymphatic leakage a scintiscan with 123I
      iodinephenylpentadekanacid-marked cream verified the presumption of a lymph
      fistula at the level of T12/L1, originating from the thoracic duct. By permanent
      draining of the posterior fistula without suction and strict intravenous
      alimentation the fluid production decreased continuously and finally ceased
      completely. Simultaneously, the neurologic state improved gradually without
      returning to normal completely. CONCLUSIONS: This case demonstrates that
      paraplegia can develop due to chylous leakage into the spinal canal without
      obvious retroperitoneal or intrathoracic involvement. This differential diagnosis
      should be kept in mind when treating patients with abundant fluid drainage into
      or from the spinal canal.

PMID- 14722424
TI  - Bipartite atlas with os odontoideum: case report.
AB  - STUDY DESIGN: A case report of bipartite atlas associated with os odontoideum and
      review of the pertinent literature are presented. OBJECTIVE: To illustrate an
      unusual association of bipartite atlas and os odontoideum and explain the
      embryological basis. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, only
      one case of bipartite atlas with os odontoideum had been reported previously.
      Most of the previously reported cases of bipartite atlas are asymptomatic.
      METHODS: A 16-year-old boy presented with a 2-month history of weakness and
      numbness of all four limbs after sustaining a minor head trauma. Radiographs of
      cervical spine revealed aplasia of anterior arch of atlas, ventral displacement
      of C1 over C2 on flexion, which reduced on extension. CT scan showed anterior
      arch aplasia, posterior arch midline defect, and os odontoideum, which had a
      small projection on the anterior surface at the level of anterior arch. MRI
      demonstrated increased cord signal at C1-C2 levels on T2-weighted image.
      Transoral odontoidectomy and posterior fixation of occiput with C2-C3 spinous
      processes was performed. RESULTS: The patient had significant improvement over
      next 3 months. CONCLUSIONS: We described a rare association of an anterior arch
      aplasia, posterior arch defect and os odontoideum. The natural history of
      patients with os odontoideum suggests that these people have a potentially
      precarious existence.

PMID- 14722428
TI  - Supporting post-MI recovery in patients with diabetes.

PMID- 14722431
TI  - How technology affects your risk of medication errors.

PMID- 14722432
TI  - Postcards from the past: a salute to nursing specialists.

PMID- 14722433
TI  - Patient education guide. Pacemakers.

PMID- 14722434
TI  - Pump away angina with EECP.

PMID- 14722435
TI  - Recognizing chronic renal failure...the sooner, the better.

PMID- 14722436
TI  - No restraints allowed: legalities and realities.

PMID- 14722437
TI  - A walk at sundown.

PMID- 14722438
TI  - What you need to know about SARS now.

PMID- 14722439
TI  - Acute peripheral arterial occlusion.

PMID- 14722440
TI  - Virus dynamics and immune responses during treatment in patients coinfected with
      hepatitis C and HIV.
AB  - Mathematical modeling of the biological effect of interferon on virus decay
      permits the quantification of the efficacy (epsilon) of blocking virion
      production in different patient populations. The viral dynamic and immunologic
      responses of hepatitis C virus (HCV) infection to daily interferon therapy were
      characterized in twelve patients co-infected with human immunodeficiency virus
      (HIV). Three out of the twelve patients (25%) achieved an early viral response, a
      two-log reduction in HCV RNA by week 12. The mean epsilon of IFN-alpha in
      blocking HCV and HIV production were 72% and 74%, respectively. For HCV epsilon
      was highest (97%) in the one patient who had a sustained viral response, while it
      was reduced in the other two patients (68% and 77%). Baseline HCV RNA and the
      number of CD3+CD56+16+ cells were inversely related (r = -0.89, p = 0.03), and
      baseline HCV-specific immune responses were significantly higher in the three
      patients with 2-log viral load reductions. These data suggest that: 1) interferon
      efficacy at blocking virion production is correlated with treatment outcome in
      HIV/HCV co-infected patients, 2) that immunodeficient patients can respond to
      standard IFN-alpha, 3) that both innate and adaptive immune responses may be
      important determinants of HCV RNA decline in response to interferon.

PMID- 14722441
TI  - Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1
      infected patients.
AB  - Memory B cells are long-living cells that circulate throughout the body and
      differentiate into plasma cells after stimulation by antigens, cytokines, and
      direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients,
      we assessed whether in vitro polyclonal B cell activation that induces
      immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B
      cells to synthesize antibodies specific to HIV-1. To this end, highly purified B
      cells from 10 HIV-1-untreated patients were cultured with or without mouse
      fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10.
      The percentage of immunoglobulin SCs we obtained by using the B cell-CD40L
      stimulation system was equal to 55% to 98% of the circulating memory B cells.
      Moreover, the anti-HIV-1 IgG, IgA, or IgM antibody SCs represented 1 x 10-2 to 1
      x 10-3 of the total immunoglobulin SCs. The anti-HIV-1-specific antibodies
      detected in cell culture supernatants were directed to gag-, pol-, and env
      encoded viral proteins. We found that in AIDS patients, HIV-1-specific resting
      memory B cells circulate in the blood and can be quantified by their anti-HIV-1
      antibody secretion after strong B cell polyclonal stimulation.

PMID- 14722442
TI  - Serious adverse cutaneous and hepatic toxicities associated with nevirapine use
      by non-HIV-infected individuals.
AB  - BACKGROUND: Nevirapine is a nonnucleoside reverse transcriptase antiretroviral
      agent. Among HIV-infected individuals, rare instances (<1%) of serious cutaneous
      and hepatic toxicity have been reported. Because of its favorable pharmacokinetic
      profile, non-HIV-infected individuals have received nevirapine-containing
      postexposure prophylaxis (PEP). OBJECTIVE: To describe the clinical features of
      cutaneous and hepatic toxicity that occurred when nevirapine was administered to
      non-HIV-infected individuals. METHODS: Reports of nevirapine-associated cutaneous
      or hepatic toxicity occurring among non-HIV-infected individuals were obtained
      from the US Food and Drug Administration's adverse event reporting system, the
      pharmaceutic manufacturer, occupational health programs in Chicago, physicians,
      and case reports. The Eastern Cooperative Oncology Group (ECOG) scoring system
      was used to grade toxicity. RESULTS: Twelve non-HIV-infected individuals
      developed severe cutaneous toxicity, including 3 with Stevens-Johnson syndrome,
      after 7 to 12 days of nevirapine-containing PEP regimens. Thirty non-HIV-infected
      individuals developed hepatotoxicity after 8 to 35 days of single-agent
      nevirapine (n = 8) or a nevirapine-containing PEP regimen (n = 22). Findings
      included ECOG grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes
      (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an
      orthotopic liver transplant (n = 1). Rates of severe hepatotoxicity (grade 3 or
      4) in non-HIV-infected individuals ranged from 10% (4/41) to 62% (5/8). Liver
      biopsy material from 2 individuals was consistent with a hypersensitivity
      syndrome. CONCLUSIONS: Serious hepatic and cutaneous toxicities can occur in non
      HIV-infected individuals who receive short-term nevirapine therapy. The rate of
      severe hepatotoxicity appears to be greater in non-HIV-infected individuals than
      in HIV-infected persons and may be associated with higher CD4 counts. The use of
      PEP regimens containing nevirapine should be discouraged.

PMID- 14722443
TI  - Characterization of nevirapine resistance mutations in women with subtype A vs. D
      HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012).
AB  - OBJECTIVE: To compare the number and type of nevirapine (NVP) resistance
      mutations detected in Ugandan women with subtype A vs. D HIV-1 infection after
      single-dose NVP prophylaxis. DESIGN: In the HIVNET 012 trial, a higher rate of
      NVP resistance (NVPR) was seen in women with subtype D than A after single-dose
      NVP. In this study, the number and type of NVPR mutations detected 6-8 weeks
      after NVP were compared in women with subtypes A vs. D. METHODS: Plasma samples
      were available for 282 (92%) of 306 women who received NVP in HIVNET 012. Samples
      were analyzed with the ViroSeq HIV-1 Genotyping System (Applied Biosystems,
      Foster City, CA). Subtyping was performed by phylogenetic analysis of pol region
      sequences. RESULTS: Results were obtained for 279 women, including 147 with
      subtype A, 98 with subtype D, 6 with subtype C, and 28 with recombinant HIV-1.
      NVPR mutations were detected in 70 (25%) of 279 women. NVPR was more common in
      women with subtype D vs. A (35.7 vs. 19%, P = 0.0035). Complex patterns of NVPR
      mutations were detected in both subtypes. Among women with NVPR, 43% of women
      with subtype A and 46% of women with subtype D had >/=2 NVPR mutations. The mean
      number and pattern of NVPR mutations detected in women with subtypes A and D were
      similar. CONCLUSIONS: This study confirms a higher rate of NVPR in women with
      subtype D than A and further defines the pattern of NVPR mutations that emerge 6
      8 weeks after single-dose NVP prophylaxis in these subtypes.

PMID- 14722444
TI  - Psychomotor slowing in hepatitis C and HIV infection.
AB  - BACKGROUND: Both HIV and hepatitis C virus (HCV) may enter the central nervous
      system and cause cognitive and/or motor dysfunction. There are limited data on
      cognition and no data on motor performance in HIV/HCV-coinfected patients.
      OBJECTIVE: To provide data on cognition and motor performance in HIV/HCV infected
      patients. METHODS: We compared 43 HIV-seropositive but HCV-seronegative patients,
      43 HIV/HCV-coinfected patients, and 44 HIV-negative but HCV-positive patients,
      all of whom went through neuropsychologic testing and electrophysiologic
      assessment of basal ganglia-mediated motor function. RESULTS: No significant
      differences could be found among the groups with regard to premorbid verbal and
      actual nonverbal intelligence, attention, and memory; the HIV dementia scale; and
      all somatic and most psychiatric complaints. Affective disorders were less
      frequent in HIV-negative but HCV-positive patients. This group also scored lower
      for depression. For all 3 groups, significant pathologic slowing of most rapid
      alternating movements (right hand) compared with those of HIV/HCV-negative
      controls as well as significantly prolonged contraction times (both hands) could
      be diagnosed. Simple reaction times were significantly prolonged only in HIV/HCV
      coinfected patients. CONCLUSIONS: Although clinically asymptomatic, both HIV
      positive and HCV-positive patients may show affective disturbances and
      significant psychomotor slowing. A potential predictive value for the further
      course of infection, which is well established in HIV-positive patients, remains
      to be investigated in HCV-positive or HIV/HCV-coinfected patients.

PMID- 14722445
TI  - Tolerance and safety of different concentrations of chlorhexidine for peripartum
      vaginal and infant washes: HIVNET 025.
AB  - BACKGROUND: There is a continuing need to evaluate sustainable interventions for
      prevention of mother-to-child transmission (MTCT) of HIV type 1. We evaluated
      different concentrations (0.25%, 1%, and 2%) of chlorhexidine (CHX) for perinatal
      maternal and infant washes to identify the maximum tolerable concentration of CHX
      for such an intervention. METHODS: Women were enrolled during their third
      trimester at the maternity unit of the Chris Hani Baragwanath Hospital in Soweto,
      South Africa, and perinatal maternal and infant washes were completed. Subjective
      maternal symptoms as well as infant examinations were used to assess tolerability
      of the washes. RESULTS: The 0.25% concentration of CHX was well tolerated by the
      mothers (n = 29). Ten of 79 women (13%) with 1% CHX washes complained of mild
      vaginal area burning or itching, and washes were stopped in 5 (6%). Twenty-three
      of 75 women (31%) in the 2% CHX wash group had subjective complaints, and the
      washes were stopped in 12 (16%). There were no clinical indications of toxicity
      of the CHX washes among infants. CONCLUSION: A 1% solution of CHX appears to be a
      safe and tolerable concentration of CHX for consideration in an MTCT prevention
      trial.

PMID- 14722446
TI  - Comparative efficacy of topical therapy with a slow-release mucoadhesive buccal
      tablet containing miconazole nitrate versus systemic therapy with ketoconazole in
      HIV-positive patients with oropharyngeal candidiasis.
AB  - This randomized comparative study assessed the efficacy and safety of a 10-mg
      once-daily topical regimen of miconazole nitrate mucoadhesive buccal tablet (n =
      178) versus a 400-mg once-daily systemic regimen of ketoconazole (n = 179) in HIV
      positive patients with oropharyngeal candidiasis. A total of 357 patients were
      treated for 7 or 14 days depending on response after 7 days of treatment.
      Clinical response was the primary outcome variable, and secondary outcomes
      included microscopy, time to cure, symptom scores, and safety outcomes. A per
      protocol analysis of 332 patients demonstrated that miconazole nitrate was not
      statistically significantly inferior to ketoconazole treatment. At day 7, the
      clinical response rate was 135 of 156 (87%) for miconazole nitrate and 137 of 153
      (90%) for ketoconazole (90% confidence interval of the treatment difference: [
      9%; 3%]). At the end of treatment, dysphagia was 1% in both groups. Microscopic
      findings paralleled the clinical results. The mucoadhesive tablet was generally
      well tolerated. A higher incidence of gastrointestinal disorders and drug-related
      adverse events was seen during ketoconazole treatment. The low-dose 10-mg
      miconazole mucoadhesive tablet is not inferior to systemic antifungal treatment
      with ketoconazole in the treatment of AIDS-related oropharyngeal candidiasis with
      and without dysphagia. It provides the first and only once-daily topical
      treatment option and should therefore be considered in first-line therapy for
      this condition, particularly in resource-poor settings, where ease of use can
      help to guarantee the success of therapy.

PMID- 14722447
TI  - Rapid HIV testing of women in labor: too long a delay.
AB  - For HIV-infected women who have not received antiretroviral treatment or
      transmission prophylaxis in pregnancy, starting antiretrovirals in labor or soon
      after birth can still decrease the risk of perinatal transmission. There is,
      therefore, potential benefit in conducting rapid HIV testing in labor, but
      hospitals are seldom prepared to conduct such testing. We compared protocols for
      rapid HIV testing at 2 hospitals to determine what proportion of women had
      results back early enough to intervene if results had been positive. Hospital A
      initially used HIV enzyme-linked immunosorbent assays (ELISAs) and changed to
      using rapid tests (eg, Single Use Diagnostic System [SUDS]); hospital B used only
      the SUDS. With use of the SUDS in hospital A, results were reported more quickly
      than with the ELISA protocol in the same hospital (P < 0.0001). Comparing use of
      the SUDS in the 2 hospitals, test results were available more quickly in hospital
      A than hospital B (P < 0.05), which resulted in hospital A having more results
      reported prior to delivery (64% vs. 38%, P < 0.05) and within 12 hours
      postdelivery (94% vs. 73%, P < 0.05). If HIV testing in labor is to have its
      maximum effect on decreasing the risk of perinatal HIV transmission, hospitals
      need to institute rapid HIV testing, but protocols must ensure that results are
      available as quickly as possible.

PMID- 14722448
TI  - Detection of nevirapine in plasma using thin-layer chromatography.
AB  - BACKGROUND: Nevirapine (NVP) is widely prescribed in resource-poor settings to
      pregnant women for treatment and prevention of HIV infection. High rates of
      misreported adherence, however, have compelled clinicians to find alternative
      methods to ensure systemic drug exposure. This report describes a fast,
      inexpensive thin-layer chromatography (TLC) method to detect the presence of NVP
      in human plasma. METHODS: Human plasma was spiked with various concentrations of
      NVP. NVP was subsequently isolated using solid-phase extraction and visualized
      with TLC. Clinical samples with NVP concentrations predetermined by high
      performance liquid chromatography were used to validate the TLC method. RESULTS:
      NVP was detected at concentrations as low as 60 ng/mL. The lower limit of
      detection was set at 100 ng/mL due to the clear spot definition at this
      concentration. The turnaround time for assay results averages several hours, and
      costs associated with the assay are considerably below standard drug quantitation
      techniques. CONCLUSION: TLC provides a rapid, sensitive, and economical tool to
      qualitatively measure NVP in plasma. This method offers clinicians in resource
      poor settings an alternative approach for measuring adherence, particularly in
      developing-world regions where NVP use is common and there is an immediate need
      to prevent mother-to-child HIV transmission.

PMID- 14722449
TI  - "Informed altruism" and "partner restriction" in the reduction of HIV infection
      in injecting drug users entering detoxification treatment in New York City, 1990
      2001.
AB  - OBJECTIVE: To assess recent developments in the HIV epidemic in injecting drug
      users (IDUs) in New York City. With >50,000 cases of AIDS in IDUs, New York has
      experienced the largest HIV/AIDS epidemic in IDUs of any city in the world.
      METHODS: Serial cross-sectional surveys conducted continuously from 1990 to 2001
      of IDUs entering the Beth Israel Medical Center (BIMC) drug detoxification
      program in New York City. HIV serostatus, use of prevention services, and risk
      behaviors were measured. Individuals were permitted to participate multiple times
      in the surveys but not more than once in any year. RESULTS: Two thousand eight
      hundred eighty-seven individuals contributed 3100 observations from 1990 to 2001.
      There was a substantial and consistent decline in the prevalence of HIV infection
      among IDUs entering the BIMC detoxification program, from 54% (165/304) in 1991
      to 13% (39/303) in 2001 (P < 0.0001). The decline was highly linear, with r2 =
      0.92 and a slope of -3.7% in seroprevalence per year. The decline occurred for
      both males and females, both short and long-term IDUs, and the three largest
      racial/ethnic subgroups (all P < 0.001 by Cochran-Armitage testing). Use of HIV
      prevention services increased substantially, particularly syringe exchange and
      voluntary HIV counseling and testing. General reductions in injection risk
      behaviors occurred, but substantial numbers of IDUs continued to engage in both
      receptive and distributive syringe sharing. Two conditional types of risk
      reduction not currently recommended by health authorities were reported:
      "informed altruism," in which persons who knew that they were HIV seropositive
      reduced transmission behavior, and "partner restriction," in which persons who
      shared needles and syringes primarily confined this sharing within small social
      networks. CONCLUSIONS: HIV infection continues to decline in this population of
      IDUs in New York City, suggesting the possibility of bringing very high
      prevalence epidemics under control. Risk elimination may not be required; rather,
      multiple forms of risk reduction may be effective in reducing HIV transmission
      within a local population of IDUs.

PMID- 14722450
TI  - Prevention of HIV transmission through breast-feeding: strengthening the research
      agenda.
AB  - Mother-to-child transmission of HIV through breast-feeding is the remaining
      challenge facing mothers in resource-poor settings with a high HIV prevalence.
      Nearly all infants in developing countries are initially breast-fed, and most
      children continue to receive some breast-feeding until at least 6 months of age
      but frequently into the 2nd year of life, especially in sub-Saharan Africa and
      Asia. In December 2002, international researchers convened in Ghent, Belgium, to
      discuss mechanisms for, rates and risk factors of, and approaches to prevention
      of HIV transmission through breast-feeding. Four papers were compiled bringing
      together the presentation and discussions during this workshop, while the fourth
      paper also benefits from presentation made during an earlier workshop on vaccines
      in the prevention of mother-to-child transmission. These papers summarize the
      current state of knowledge and highlight the outstanding issues that will need to
      be addressed in the very near future before research advances can be translated
      into public health practice.

PMID- 14722451
TI  - Immunoprophylaxis to prevent mother-to-child transmission of HIV-1.
AB  - Antiretroviral therapy can profoundly reduce the risk of mother-to-child
      transmission (MTCT) of HIV, but the drugs have a relatively short half-life and
      should thus be administered throughout breast-feeding to optimally prevent
      postnatal infection of the infant. The potential toxicities and the development
      of resistance may limit the long-term efficacy of antiretroviral prophylaxis, and
      a safe and effective active/passive immunoprophylaxis regimen, begun at birth,
      and potentially overlapping with interpartum or neonatal chemoprophylaxis, would
      pose an attractive alternative. This review draws on data presented at the Ghent
      Workshop on prevention of breast milk transmission and on selected issues from a
      workshop specifically relating to immunoprophylaxis held in Seattle in October
      2002. This purpose of this review is to address the scientific rationale for the
      development of passive (antibody) and active (vaccine) immunization strategies
      for prevention of MTCT. Data regarding currently or imminently available passive
      and active immunoprophylaxis products are reviewed for their potential use in
      neonatal trials within the coming 1-2 years.

PMID- 14722452
TI  - Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding:
      from animal studies to randomized clinical trials.
AB  - The major remaining challenge in the prevention of mother-to-child transmission
      is the reduction of the risk in settings where breast-feeding is common. This
      review gives an update on ongoing or planned antiretroviral intervention studies
      in resource-limited settings that are aimed at reducing the risk of mother-to
      infant HIV transmission during lactation. These strategies include antiretroviral
      therapy given to the mother to reduce viral load in plasma and breast milk as
      well as antiretroviral regimens providing prophylaxis to uninfected infants
      during the period of breast-feeding. The rationale for the interventions based on
      animal models and human studies is described as well as the study designs of
      clinical trials. Potential risks and benefits of these interventions to mothers
      and infants are also highlighted. Laboratory studies nested within several of
      these trials will provide a better understanding of the pathogenesis of postnatal
      HIV transmission and its potential prevention using antiretroviral drugs.

PMID- 14722453
TI  - Preventing postnatal transmission of HIV-1 through breast-feeding: modifying
      infant feeding practices.
AB  - Approaches to reducing or preventing the risk of postnatal transmission through
      breast-feeding include the avoidance of all breast-feeding and the use of
      exclusive replacement feeds or exclusive breast-feeding for a limited duration
      with early and rapid cessation of breast-feeding around 4-6 months of age. The
      efficacy and safety of the latter approach have not been established and studies
      are in progress to provide further information. In addition, inactivation of HIV
      in breast milk would allow breast-feeding to continue while reducing the risk of
      postnatal transmission of HIV and may be usefully applied in certain
      circumstances, such as for premature infants or while a mother recovers from
      mastitis. In this review, experience is reported from clinical trials or studies
      additional to their main objective of assessing rates and risk factors for mother
      to-child transmission. This may inform policy, programming, and training options
      and may be especially valuable in the absence of conclusive data on the efficacy
      of the interventions to be applied during the breast-feeding period.

PMID- 14722455
TI  - Is the influence of social desirability on patients' self-reported adherence
      overrated?

PMID- 14722454
TI  - Breast-feeding and Transmission of HIV-1.
AB  - Breast-feeding substantially increases the risk of HIV-1 transmission from mother
      to child, and although peripartum antiretroviral therapy prophylaxis
      significantly decreases the risk of mother-to-child transmission around the time
      of delivery, this approach does not affect breast-feeding transmission. Increased
      maternal RNA viral load in plasma and breast milk is strongly associated with
      increased risk of transmission through breast-feeding, as is breast health, and
      it has been suggested that exclusive breast-feeding could be associated with
      lower rates of breast-feeding transmission than mixed feeding of both breast- and
      other milk or feeds. Transmission through breast-feeding can take place at any
      point during lactation, and the cumulative probability of acquisition of
      infection increases with duration of breast-feeding. HIV-1 has been detected in
      breast milk in cell-free and cellular compartments; infant gut mucosal surfaces
      are the most likely site at which transmission occurs. Innate and acquired immune
      factors may act most effectively in combination to prevent primary HIV-1
      infection by breast milk.

PMID- 14722456
TI  - Efficacy and tolerability of zalcitabine twice daily (HIVBID Study).

PMID- 14722457
TI  - Differences in frequencies of drug resistance-associated mutations in the HIV-1
      pol gene of B subtype and BF intersubtype recombinant samples.

PMID- 14722458
TI  - Recent increase in high-risk sexual behaviors among sexually active men who have
      sex with men living with AIDS in Los Angeles County.

PMID- 14722459
TI  - Red eyes, melting corneas, and gene therapy: some editorial thoughts.

PMID- 14722460
TI  - Recombinant human tumor necrosis factor receptor Fc fusion protein (Etanercept):
      experience as a therapy for sight-threatening scleritis and sterile corneal
      ulceration.
AB  - PURPOSE: To review the efficacy of Etanercept as an alternate therapy for
      treatment of necrotizing anterior scleritis and sterile corneal ulceration
      unresponsive to traditional therapies. METHODS: A retrospective review of 10
      patients treated with Etanercept for vision-threatening scleritis and sterile
      corneal ulceration. RESULTS: Etanercept alone or in combination with other
      immunosuppressive therapies controlled inflammation, arrested tissue ulceration,
      and in many cases permitted tapering or cessation of toxic immunosuppressive
      therapies. No complications or systemic toxicity were observed with Etanercept
      use. CONCLUSION: Etanercept is an effective treatment for scleritis and sterile
      corneal ulceration and has a favorable benefit-to-risk ratio. It may be
      considered for therapy of progressive disease or cases that are unresponsive to
      traditional therapies.

PMID- 14722461
TI  - Effect of 30-day continuous wear of silicone hydrogel contact lenses on corneal
      thickness.
AB  - PURPOSE: To investigate the effect of 30-day continuous-wear contact lenses
      (Focus Night & Day) on corneal thickness and physiology. METHODS: Twenty-six
      myopic eyes with no history of contact lens wear were fitted with silicone
      hydrogel contact lenses. Complete ophthalmologic examinations, corneal
      topography, and corneal thickness measurements at the center and eight peripheral
      areas were performed before fitting and at each visit, namely on day 1, day 10,
      and 1 month. Mean corneal thicknesses were statistically compared by using one
      way repeated-measures analysis of variance. RESULTS: All patients maintained
      their 20/20 vision with correction. Limbal vascularization was noted in one
      patient at the end of the study. No patient had subjective complaints. In another
      patient, a punctate corneal epithelial defect was noted on the 15th day, but it
      healed when the contact lens was removed for a day. The mean corneal thicknesses
      in different regions were significantly increased by approximately 14 to 38
      microm compared with baseline measurements. There were no significant differences
      between the corneal topography taken on the first day and the one taken at the
      end of the first month. CONCLUSIONS: All patients maintained their visual acuity.
      Apart from the limbal vascularization and punctate epithelial corneal defects,
      which resolved when the contact lens was removed for 1 day, no serious
      complications were noted. Despite the high oxygen permeability of the monthly
      Night & Day contact lenses, the mean central and peripheral corneal thicknesses
      increased. These increases indicate that these lenses may have an effect on
      corneal metabolism.

PMID- 14722462
TI  - Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and
      perennial allergic conjunctivitis.
AB  - PURPOSE: To determine the long-term safety of the topical steroid, loteprednol
      etabonate 0.2%, in the treatment of seasonal and perennial allergic
      conjunctivitis. METHODS: A retrospective review of 397 patients from three
      private ophthalmologic practices treating seasonal and perennial allergic
      conjunctivitis with long-term loteprednol etabonate 0.2% was performed. Chart
      review of slitlamp findings and intraocular pressure measurements during follow
      up visits was performed to determine the incidence of adverse effects, such as
      steroid-induced intraocular pressure increase, cataract formation, and any other
      possible topical steroid-induced adverse event. One hundred fifty-nine of the 397
      patients had been continuously using loteprednol for more than 12 months.
      RESULTS: There were no reported adverse effects of long-term loteprednol
      etabonate 0.2% use in any of the 159 patients, whose continuous use ranged from a
      cumulative total of 120 drops per eye to 3,741 drops per eye. CONCLUSIONS:
      Loteprednol etabonate 0.2% is a safe topical steroid when used on a long-term
      basis for the treatment of seasonal and perennial allergic conjunctivitis.

PMID- 14722463
TI  - Conservative treatment of meibomian gland dysfunction.
AB  - PURPOSE: To evaluate the effectiveness of lid hygiene and preservative-free
      artificial tears for the treatment of meibomian gland dysfunction (MGD) during a
      6-week period. METHODS: Suitable patients with MGD were educated about their
      disease and instructed to begin a regimen of lid hygiene, which included the
      application of a heated saline solution and the use of nonpreserved artificial
      tears. Baseline measurements obtained at the time of enrollment included basic
      tear secretion test, tear breakup time, a questionnaire grading MGD symptoms
      (i.e., burning, irritation, itching, sharp pains, foreign body sensation, and
      hazy vision), and lid margin slitlamp photographs. All measurements except for
      basic tear secretion were repeated at the 6-week follow-up visit. Photographs
      were unlabeled, and two cornea specialists graded them in a masked fashion for
      the presence of lid erythema, irregularity, thickness, meibomian gland capping,
      and telangiectasis. RESULTS: Thirty-seven patients with a clinical diagnosis of
      MGD were enrolled, and 26 patients (70%) completed the study. Initial measurement
      of basic tear secretion averaged 17 mm and was more than 10 mm in 81% of eyes.
      The tear breakup time was prolonged by an average of 3.4 seconds; in 30% of
      cases, it was normalized to 10 seconds or more. Symptoms improved in 88% of
      cases; among those, symptoms were graded mild or less in 83%, and none in 39%.
      Photographs before and after treatment were not significantly different.
      CONCLUSIONS: In this noncontrolled case-cohort study of selected patients with
      MGD, lid hygiene and preservative-free artificial tears significantly improved
      tear breakup time and relieved symptoms of the condition.

PMID- 14722464
TI  - Clinical performance and fitting characteristics with a multicurve lens for
      keratoconus.
AB  - PURPOSE: To evaluate the clinical outcome and fitting characteristics with a
      multicurve lens for keratoconus in a Korean population. METHODS: Sixty eyes with
      keratoconus were fit with a multicurve lens based on topographic index and
      fluorescein pattern on slitlamp biomicroscopy. Three-point touch was applied in
      59 eyes, and apical clearance was adopted in an eye with a persistent epithelial
      defect. The mean follow-up was 11.4 months. Visual acuity, comfort, glare, daily
      contact lens-wearing time, and the changes in topographic indices after fitting
      were evaluated. The relationship between base curve radius (BCR) and topographic
      indices were analyzed along with the relationship between BCR and peripheral
      curve radius. RESULTS: A total of 71.6% of the eyes achieved a visual acuity of
      20/30 or better. Flatter BCR was related to better visual acuity. Ninety-four
      percent of the patients tolerated the fitting, and 85% of them reported complete
      comfort. The mean daily wearing time was 11.9 hours. Four eyes reported glare.
      The change of Sim K during follow-up was not statistically significant.
      Prefitting Sim Kmax and average Sim K were significantly related to the BCR. Mean
      differences between the BCR and first peripheral curve radius were 1.06 +/- 0.21
      mm with a BCR less than 6.00 mm and 0.81 +/- 0.2 mm with a BCR greater than 6.00
      mm. These differences were statistically significant. CONCLUSIONS: Customization
      with the multicurve lens enabled patients with keratoconus to wear the contact
      lens comfortably and seemed not to aggravate the progression of keratoconus. Sim
      Kmax and the relationship between BCR and first peripheral curve radius seem to
      be useful information to optimize performance of the multicurve lens.

PMID- 14722465
TI  - Survey of bandage lens use in North America, October-December 2002.
AB  - PURPOSE: The purpose of this work was to report the findings of a survey of
      current modes of bandage lens (BL) use by optometrists and ophthalmologists in
      Canada and the United States in 2002. METHODS: Two thousand voluntary surveys
      were sent to ophthalmic practitioners across the United States and Canada. The
      survey contained a questionnaire with 15 questions about the practitioner's
      background and BL-prescribing trends and views. It also contained a 10-patient
      list with parameters such as patient profile, BL type, and pharmaceutical use.
      RESULTS: Seventy-two percent of those opthalmic practitioners who returned
      surveys have prescribed soft contact lenses for therapeutic purposes. BLs are
      most often used for corneal wound healing and for managing postoperative
      complications. Pharmaceuticals are concomitantly administered in more than 81% of
      the patients treated with BLs. The most commonly prescribed pharmaceuticals are
      antibiotics (47.5% of patients) and antiinflammatory drugs (42% of patients).
      ACUVUE and Focus Night & Day lenses are the most popular choices for BLs. Most
      respondents (93%), regardless of whether they routinely prescribed BLs, would be
      interested in a BL that could deliver a topical pharmaceutical drug. CONCLUSIONS:
      The results from the survey indicated that BL use is prevalent across North
      America. The BL-prescribing habits of North American practitioners indicate that
      there is a strong interest and need for a drug-delivering therapeutic soft
      contact lens.

PMID- 14722466
TI  - Fitting contact lenses for visual rehabilitation after penetrating keratoplasty.
AB  - PURPOSE: To determine the optical indications for contact lens wear after corneal
      transplantation. The type of lenses used, fitting philosophy, visual outcomes,
      and complications were examined. METHODS: A 4-year retrospective chart review was
      performed and identified 35 eyes in 30 patients wearing contact lenses for visual
      rehabilitation after penetrating keratoplasty. RESULTS: The optical indications
      for contact lens fitting after penetrating keratoplasty were multifactorial and
      included irregular astigmatism (62.9%), spherical anisometropia (57.1%), and
      astigmatic anisometropia (54.3%). The average time from surgery to initial
      contact lens fitting was 18.2 months. Spherical rigid gas-permeable lenses were
      the most common type of lens used. The mean best-corrected visual acuity improved
      from less than 20/40 with spectacles alone to better than 20/30 when using a
      contact lens. Punctal occlusion and lubrication helped to improve contact lens
      tolerance. Complications associated with contact lens use tended to be minor and
      responded generally well to conservative treatment measures. CONCLUSION: Contact
      lenses can improve visual function in patients with irregular astigmatism and
      anisometropia after penetrating keratoplasty.

PMID- 14722467
TI  - Effect of povidone 2% preservative-free eyedrops on contact lens wearers with
      computer visual syndrome: pilot study.
AB  - PURPOSE: To show that the use of povidone 2% preservative-free lubricating
      eyedrops reduces computer visual syndrome in contact lens wearers and to identify
      the best eyedrop instillation protocols. METHODS: The test product was FILMABAK a
      CE-marked nonpreserved lubricant, povidone 2% delivered by the ABAK system. Three
      dispensing modalities were evaluated during contact lens wear and computer use:
      hourly instillation, symptom-related instillation, and patient's own
      instillation. RESULTS: During sustained computer use, a decrease in symptoms
      associated with the use of povidone 2% was statistically and clinically
      significant. However, the symptoms were not fully eliminated by the use of the
      test eyedrop. The three instillation routines achieved similar beneficial
      effects. No significant changes in ocular tissue response were observed, and the
      staining recorded after sustained computer use remained low. The use of povidone
      2% preservative-free lubricating eyedrops under any of the three instillation
      modalities tested was also associated with a slight improvement in dynamic visual
      acuity. CONCLUSIONS: The use of povidone 2% preservative-free eyedrops was
      associated with an improvement in symptoms during sustained computer use. Any of
      the three instillation modalities decreased symptoms of ocular tiredness,
      dryness, and difficulty of focus; maintained an unchanged corneal surface; and
      improved dynamic visual acuity. Therefore, the most patient-friendly modality
      (patient's own instillation modality from symptom onset) could be recommended to
      contact lens wearers with computer visual syndrome.

PMID- 14722468
TI  - Spontaneous bilateral corneal perforation of acute hydrops in keratoconus.
AB  - PURPOSE: To report an uncommon case of bilateral spontaneous corneal perforation
      in keratoconus. DESIGN: Interventional case report. METHOD: A 63-year-old man
      with a long history of keratoconus (more than 30 years) experienced acute hydrops
      and corneal perforation in his right eye. One year later, he had the same
      clinical features in his left eye. RESULTS: After initial treatment with
      cyanoacrylate glue and bandage soft contact lenses, therapeutic penetrating
      keratoplasty was performed with good visual outcome in both eyes. CONCLUSION:
      Special attention should be paid to the possibility of spontaneous corneal
      perforation during acute hydrops in patients with severe corneal thinning,
      biomicroscopic findings of advanced disease, and high keratometry readings.

PMID- 14722469
TI  - Disinfection capacity of PuriLens contact lens cleaning unit against
      Acanthamoeba.
AB  - PURPOSE: The PuriLens contact lens system is indicated for cleaning and
      disinfection of soft (hydrophilic) contact lenses by means of subsonic agitation
      to remove lens deposits and microorganisms, and ultraviolet irradiation of the
      storage solution for disinfection. The capacity of the PuriLens system to
      disinfect storage solutions contaminated with known concentrations of
      Staphylococcus aureus, Pseudomonas aeruginosa, and Acanthamoeba species was
      evaluated. METHODS: An in vitro assessment of the antibacterial and antiparasitic
      efficacy of the PuriLens system was performed. Separated batches of the storage
      solution for the cleansing system were contaminated with stock strains of S.
      aureus and P. aeruginosa. A comparison of the microbiologic content was made
      between the solution before and after the cycle. RESULTS: The PuriLens system
      effectively eradicated S. aureus and P. aeruginosa organisms after a 15-minute
      cycle. However, viable cysts of acanthamoeba were recovered in the solution after
      the 15-minute cycle. CONCLUSIONS: The PuriLens system is highly efficient in
      protecting against contamination with common bacterial ocular pathogens.
      Acanthamoeba cysts, however, can survive in the solution or contact lens bath
      undergoing integrated subsonic debridement and indirect ultraviolet light
      disinfection. Use of chemical disinfecting solutions that contain agents such as
      chlorhexidine or other cationic antiseptics may be advisable in conjunction with
      use of the PuriLens device, especially in high-risk settings.

PMID- 14722470
TI  - A hyper-Dk piggyback contact lens system for keratoconus.
AB  - PURPOSE: To report the fitting of a hyper-Dk piggyback contact lens system in a
      case of keratoconus. METHODS: Case report. RESULTS: A patient with keratoconus,
      suboptimal visual acuity, corneal neovascularization, and marked conjunctival
      hyperemia, who was intolerant of rigid gas-permeable contact lenses, was fitted
      with a novel piggyback contact lens system that incorporated a hyper-oxygen
      transmissible hydrogel contact lens, on top of which was fitted a hyper-oxygen
      transmissible rigid gas-permeable lens. This novel contact lens system provided a
      significant improvement in visual acuity, comfort, and lens wear time. There was
      a marked reduction in corneal vascularization and ocular hyperemia. CONCLUSIONS:
      This hyper-Dk piggyback contact lens system satisfied the ocular and visual
      requirements of this patient, for whom other nonsurgical options for vision
      correction had been unsuccessful. This system has potential application in the
      visual rehabilitation of other cases of corneal irregularity, including
      unsuccessful refractive surgery, ocular trauma, and keratoplasty. Piggyback
      contact lens systems require the same level of expertise to fit as basic forms of
      soft and rigid contact lenses. The hyper-oxygen transmissible lens materials
      available make these dual-lens systems a viable option for the compromised
      cornea.

PMID- 14722471
TI  - Hyperopic laser-assisted in situ keratomileusis results with LADARVision, Visx
      Star S2, and Visx Star S3.
AB  - PURPOSE: To compare the LADARVision (LV), Visx Star S3 (S3), and Visx Star S2
      (S2) excimer lasers in the treatment of spherical hyperopia and hyperopic
      astigmatism with laser-assisted in situ keratomileusis. SETTING: A parallel,
      consecutive, three-surgeon, cohort comparison was performed at Zale Lipshy
      University Hospital, Laser Center for Vision, The University of Texas
      Southwestern Medical Center at Dallas, Texas for consecutive cases between
      January 2001 and October 2001. METHODS: Treatment outcomes of 105 hyperopic eyes
      with manifest refraction spherical equivalents of up to +6.50 diopters and
      astigmatism up to 3.75 diopters were compared. Forty-one eyes were treated with
      LV; 25 eyes were treated with S3; and 39 eyes were treated with S2. Outcome
      measures included uncorrected visual acuity, best spectacle-corrected visual
      acuity, predictability, and stability of treatments at 1 week and 1, 3, and 6
      months. RESULTS: All three lasers were comparable in terms of refractive
      stability and predictability. The LV group had consistently better uncorrected
      visual acuities than did the S2 and S3 groups during the follow-up period. At 6
      months, the LV group had statistically significantly better visual results than
      the S3 group at the 20/25 and 20/20 levels, whereas the only significant
      difference between the LV and S2 groups was at the 20/25 level. Better visual
      outcomes were achieved with S2 than with S3, but the differences were not
      statistically significant. No eye lost more than one line of best spectacle
      corrected visual acuity. CONCLUSIONS: Predictability and stability of hyperopic
      laser-assisted in situ keratomileusis treatments with all three lasers were
      comparable. Visual results with LV at 6 months were statistically significantly
      better than those with S3 and S2.

PMID- 14722472
TI  - Corneal endothelial cell count in keratoconus patients after contact lens wear.
AB  - PURPOSE: The influence of contact lenses on healthy corneal endothelium has been
      well documented, but little is known about the effect of contact lens wear on the
      corneal endothelial cells of patients with keratoconus. This cross-sectional
      comparative study was conducted to determine quantitative characteristics of
      corneal endothelial cells of 100 patients with keratoconus with or without
      contact lenses. METHODS: A Humphrey Atlas corneal topographer was used to map the
      keratoconic cornea. The corneal apex of the cone was located by using the axial
      topography map. The Konan SP-9000 Noncon Robo Pachy specular microscope and the
      Konan SP-400 specular microscopes were used to photograph the endothelium at the
      apex of the cone, and the average endothelial cell count was obtained. Patients
      were categorized into four groups based on the types of contact lenses worn: no
      contact lenses, SofLens 66 toric contact lenses, SoftPerm contact lenses, and
      FluoroPerm 30 aspheric rigid gas-permeable (RGP) contact lenses. Analysis of
      variance was used to determine differences in endothelial cell counts among
      groups. RESULTS: After controlling for age and severity of keratoconus, patients
      who wore SoftPerm contact lenses had 18% lower endothelial cell counts (2,157 +/-
      442) than did patients without contact lenses (2,538 +/- 398). These patients
      also had 15% lower endothelial cell counts than did patients who wore soft toric
      disposable contact lenses (2,483 +/- 292). There was a 7% lower endothelial cell
      count in the group wearing aspheric RGP contact lenses than in the group that did
      not wear contact lenses, and a 5% lower endothelial cell count in the group
      wearing aspheric RGP contact lenses than in the group that wore soft toric
      contact lenses, but these differences were not statistically significant.
      CONCLUSIONS: Patients with keratoconus who wear SoftPerm contact lenses have a
      significantly lower endothelial cell count than those patients with keratoconus
      who do not wear lenses, or who wear soft toric disposable contact lenses or RGP
      contact lenses.

PMID- 14722473
TI  - Therapeutic use of a lotrafilcon A silicone hydrogel soft contact lens as a
      bandage after LASEK surgery.
AB  - PURPOSE: Soft contact lenses may be used as a bandage after corneal refractive
      surgery. Silicone hydrogel contact lenses offer the advantage of increased oxygen
      permeability over conventional hydrogel lenses for this application. To evaluate
      a silicone hydrogel contact lens as a continuous wear bandage applied after laser
      assisted sub-epithelial keratomileusis (LASEK). METHODS: We conducted a
      prospective, open-label, non-randomized clinical trial involving thirty patients
      treated with unilateral LASEK. Patients were fitted with a lotrafilcon A (Focus
      NIGHT & DAY; CIBA Vision, Duluth, GA) silicone hydrogel soft contact lens that
      was worn continuously for 3 to 4 days post-operatively. Lens movement and
      slitlamp evaluations of conjunctival hyperemia 1, 2, and 3 days after surgery
      (DAS) were recorded, as was the condition of the corneal epithelium after lens
      removal. Subjective comfort was rated by the patients along with the presence of
      symptoms or pain. RESULTS: Post-blink lens movement was evaluated by
      investigators as "very good" or "good" in 87% of eyes at 1 DAS, in 73% at 2 DAS,
      and in 60% at 3 DAS. Conjunctival hyperemia was assessed as normal or trace in
      96% of eyes at 1 DAS, in 76% at 2 DAS, and in 67% at 3 DAS. An average of 80% of
      eyes showed normal or trace conjunctival hyperemia during the trial. The
      condition of the corneal epithelium after contact lens removal was rated as "very
      good" in 13% or "good" in 73% of eyes. An average of 77% of subjects reported
      "very good" or "good" comfort during the trial. Symptoms or pain were rated as
      "absent" or "mild" by all subjects at 1 DAS and 2 DAS and by 96% at 3 DAS. An
      average of 99% rated symptoms or pain as either "absent" or "mild" during the
      trial. CONCLUSIONS: The lotrafilcon A lens was found to be an effective and well
      tolerated bandage lens after LASEK.

PMID- 14722474
TI  - Therapeutic use of a silicone hydrogel contact lens in selected clinical cases.
AB  - PURPOSE: To evaluate a silicone hydrogel contact lens as a continuous-wear
      bandage in selected clinical cases, a prospective, open, nonrandomized clinical
      study was conducted. METHODS: Seventy eyes from 70 patients with anterior segment
      conditions for which therapeutic lenses were indicated were enrolled in the
      study. In most patients (47 eyes, 67%), the presenting condition was bullous
      keratopathy. Patients were fitted with a lotrafilcon A silicone hydrogel lens
      (Focus Night & Day) that was worn continuously for 7 to 30 days, and the
      concomitant therapies were used. The corneal condition was assessed, and
      subjective comfort was recorded for 7 days to 18 months after fitting (mean
      follow-up, 69 days). RESULTS: Of 70 eyes, 64 (91%) showed improvement in the
      clinical condition of the eye, and 66 (94%) rated comfort when wearing the lens
      as very good or good. CONCLUSIONS: The study lens was found to be an effective
      and well-tolerated bandage lens in these selected patients.

PMID- 14722475
TI  - Corneal warpage.

PMID- 14722476
TI  - Psychiatric service utilization and cost for persons with schizophrenia in a
      Medicaid managed care program.
AB  - A pre-post study design was used to look at changes in behavioral health care
      services and costs for Medicaid-eligible individuals with schizophrenia in a
      managed care (MC) carve-out compared to a fee-for-service (FFS) program in
      Pennsylvania between 1995 and 1998. Statistically significant reductions of 59%
      were found in hospital expenditures in the MC program compared to 18.3% in the
      FFS program. The decline in hospital costs was due to dramatic fee reductions in
      the MC site. No significant differences in overall ambulatory utilization were
      found in either program; however, ambulatory expenditures rose 57% in the MC
      program versus a decline of 11% in fee for service. The ambulatory cost increase
      resulted from a cost shift between county block grant funds, and Medicaid funds,
      with no additional revenues provided to outpatient providers. Study implications
      are that cost reductions from MC are mainly due to reducing utilization and
      payments to hospitals, similar to the findings for private sector programs.

PMID- 14722477
TI  - Identifying factors critical to implementation of integrated mental health
      services in rural VA community-based outpatient clinics.
AB  - The purpose of this study was to gain a better understanding of the critical
      components associated with implementing integrated mental health care services in
      rural VA community-based outpatient clinics (CBOCs). In-person semi-structured
      interviews were conducted with 20 health care providers and staff within a year
      after placing a trained advanced practice nurse (APN) to provide mental
      health/substance abuse (MH/SA) care at 2 rural CBOCs in the southeastern United
      States. Four raters independently evaluated interview transcripts and conducted
      content analysis to summarize the interview results. The results indicate that
      key contextual factors related to leadership, staff attitudes and beliefs, and
      unique organizational factors of the clinic and the community can affect the
      success of such clinical innovations. In addition to providing descriptive
      information about the attitudes, beliefs, and experiences of CBOC personnel
      regarding implementation of integrated MH/SA services using APNs, the study
      findings suggest several domains that could be explored in future studies of
      integrated mental health service delivery to rural veterans through primary care.

PMID- 14722478
TI  - Patterns of medical resource and psychotropic medicine use among adult depressed
      managed behavioral health patients.
AB  - Medical and pharmacy utilization patterns were examined among 782 depressed
      patients seen by independent clinicians through a Managed Behavioral Health
      Organization using behavioral, medical and pharmacy claims spanning 2 years. Two
      thirds received psychiatric care in the medical and mental health sector
      concurrently, 43% had comorbid medical disorders, 61% received psychotropic
      medications, and 54% were on antidepressants. Fewer depressed medically comorbid
      patients used medical services while in mental health treatment than before or
      after treatment, while the per patient costs remained the same. For those with
      chronic conditions, medical utilization and costs remained the same. A quarter of
      depressed patients received mental health treatment before seeing a mental health
      specialist, and a quarter remained in treatment in the medical sector after
      treatment in the mental health sector. Despite increases in mental health
      services access made available through managed behavioral health organizations,
      patients continue receiving mental health treatment in the medical sector.

PMID- 14722479
TI  - Perceptions of mental health and substance abuse program administrators and staff
      on service delivery to persons with co-occurring substance abuse and mental
      disorders.
AB  - Several initiatives in the past 20 years have been implemented in Los Angeles
      County to improve service delivery across the mental health and substance abuse
      treatment systems, with the goal of increasing access to and coordination of
      services for individuals with co-occurring substance abuse and mental disorders.
      To examine the current status of service delivery to this population, a survey
      was conducted with administrators of mental health and substance abuse programs
      that provide services to dually diagnosed patients and with the treatment staff
      in those programs. Administrators (n = 15) and staff (n = 99) in substance abuse
      programs rated the accessibility and coordination of services to dually diagnosed
      patients significantly lower than the mental health administrators (n = 10) and
      staff (n = 136). Efforts to coordinate service delivery across the two systems
      need to address these divergent perceptions between staff in programs that are
      increasingly called upon to work together to jointly deliver services.

PMID- 14722480
TI  - The sensitivity of substance abuse treatment intensity to co-payment levels.
AB  - This study exploits variation in co-payment levels among different contractual
      arrangements within a regional managed behavioral health care organization to
      estimate the relationship between co-payment levels for substance use treatment
      services and the intensity of substance use treatment. The substance use
      treatment benefits involved a range of co-payment levels across nearly 400
      employers during the years 1993 through 1998. Multiple regression techniques were
      used to estimate the effect of co-payment levels on treatment intensity. The
      results indicate that co-payment levels had a significant negative effect on
      outpatient and inpatient substance use treatment. For outpatient treatment the
      effect on intensity implied a co-payment elasticity of -0.18, implying that
      moving from a $10 co-payment to a $20 co-payment would result in, for example, a
      reduction from 5 to 4 outpatient visits per episode. However, the effect was
      larger for persons with combined alcohol and drug use disorders, as they
      exhibited a co-payment elasticity of -0.27. For inpatient days, the co-payment
      elasticity was considerably smaller at -0.017. Given the benefits of maintaining
      persons with substance use disorders in treatment, employers may have an
      incentive to take steps to minimize the barriers to treatment.

PMID- 14722481
TI  - Profiling hospitals for length of stay for treatment of psychiatric disorders.
AB  - Managed behavioral health care organizations (MBHOs) often profile hospitals on
      length of stay (LOS) and other performance measures. However, previous research
      has suggested that most of the variation in utilization for general medical
      conditions is attributable to case-mix indicators and random sources rather than
      individual providers. Hospital discharge data are used to estimate hierarchical
      linear models, where hospitals and physicians within hospitals are treated as a
      random effect. The goal was to determine the intraclass correlation coefficient
      (ICC) for psychiatric LOS for hospitals and for physicians before and after
      making case-mix adjustments. After controlling for case-mix, the hospital ICCs
      for depression, schizophrenia, and bipolar disorder show that 32%, 36%, and 11%
      of the variation in LOS, respectively, can be attributed to hospitals, while 7%,
      5%, and 6% of the variation in LOS, respectively, can be attributed to physicians
      or provider practice. Unlike health services for other conditions, the variation
      in LOS for inpatient psychiatric treatment of depression and schizophrenia is
      quite dependent upon hospitals.

PMID- 14722482
TI  - Externally caused deaths for adults with substance use and mental disorders.
AB  - For decades, there have been reports of shorter life expectancy among those with
      mental illness, especially those with more serious psychiatric disorders. The
      purpose of this study was to compare the risk of mortality among Medicaid
      beneficiaries, aged 18-64 years, treated for mental illness to a comparable group
      who were not mentally ill and to the general population. The data used were from
      the Massachusetts Division of Medical Assistance and records of deaths from the
      Department of Public Health in Massachusetts. Individuals treated for both
      psychiatric illness and substance use disorders (dual diagnoses) were compared
      separately from those whose treatment was only for a psychiatric disorder. For
      all Medicaid beneficiaries, the most common causes of death were attributed to
      heart disease and cancer. When compared to the general population, adjusted odds
      ratios estimated death by injury to be twice as likely among the mentally ill
      when compared to the general population. Medicaid beneficiaries with dual
      diagnoses are 6-8 times more likely to die of injury, primarily poisoning, than
      their counterparts treated for medical conditions only.

PMID- 14722486
TI  - Obesity and cancer. Examining the link.

PMID- 14722484
TI  - Using information to guide managed behavioral health care.
AB  - This evaluation of substance abuse and mental health treatment services in
      Arizona discusses and illustrates the use of data already collected by the State
      to manage and monitor the public behavioral health sector. The authors utilize a
      framework that focuses on rate-setting and financial incentives; provider
      profiling and education; and monitoring of data quality and system-wide
      performance. Information and analysis can contribute to key management activities
      and forces that guide behavior in the system toward optimal system performance.
      Using data from 33,208 Medicaid-covered and uninsured adults, service mix varied
      substantially by region; for example, spending on residential care ranged from 0%
      to 40% for substance abuse treatment clients. By focusing on a smaller group of
      client with functional assessments, it also appears that regional spending levels
      varied considerably, for reasons not explained by client demographics or clinical
      measures. Finally, longitudinal data show that the regional managed care
      organizations are moving in different directions with regard to client mix and
      spending priorities. All of this variation suggests that there may be
      considerable latitude to guide and improve system-wide performance.

PMID- 14722483
TI  - Designated case managers as facilitators of medical and psychosocial service
      delivery in addiction treatment programs.
AB  - This study examines whether having designated case management staff facilitates
      delivery of comprehensive medical and psychosocial services in substance abuse
      treatment programs. A multilevel, prospective cohort study of 2829 clients
      admitted to selected substance abuse treatment programs was used to study clients
      from long-term residential, outpatient, and methadone treatment modalities.
      Program directors reported whether the program had staff designated as case
      managers. After treatment discharge, clients reported their receipt of 9
      supplemental services during the treatment episode. In multivariate models
      controlling for multiple program-level and client-level factors, program-level
      availability of designated case managers increased client-level receipt of only 2
      of 9 services, and exerted no effect on service comprehensiveness, compared to
      programs that did not have designated case managers. These findings do not
      support the common practice of designating case management staff as a means to
      facilitate comprehensive services delivery in addiction treatment programs.

PMID- 14722487
TI  - Common blood pressure medication may prevent broken hips.

PMID- 14722488
TI  - New treatment for troublesome vulvar pain.

PMID- 14722489
TI  - New drug approved for irritable bowel syndrome in women.

PMID- 14722490
TI  - Female sexual dysfunction. Finding your way back to intimacy.

PMID- 14722491
TI  - Frozen shoulder. Can you help it 'thaw'?

PMID- 14722492
TI  - Popping popcorn. Make it healthy.

PMID- 14722493
TI  - I read about fish oil supplements in your September issue. Should I be concerned
      about mercury levels in these products?

PMID- 14722495
TI  - My fingernails have ridges running the length of them, and the ridges seem to be
      getting more prominent as I get older. Should I be concerned?

PMID- 14722494
TI  - Are diet soft drinks as harmful to my teeth as regular soft drinks?

PMID- 14722496
TI  - Chronic cough.

PMID- 14722497
TI  - Are indoor molds causing a new disease?
AB  - Three mechanisms for disease caused by mold-infection, allergy, and toxicity-are
      established and well recognized by clinicians. In each case the corresponding
      diseases are specific to a particular fungus. The mechanisms involved include a
      recognized inflammatory pathology that leads to objective clinical evidence of
      disease. Recent widespread litigation has arisen out of an unproved assertion
      that exposure to indoor molds causes an ill-defined illness. This illness is
      characterized by the absence of objective evidence of disease and by the lack of
      a defined pathology. There is usually no specificity for the involved fungus
      purported to cause the illness. Those publications that claim such an illness are
      reviewed. They are found to lack scientific validity, often on the basis of
      faulty methodology and insufficient information. There is no coherent clinical
      description for the presumed illness. Recommendations are offered for published
      reports and studies to address this problem.

PMID- 14722498
TI  - Writing for publication: your obligation to the profession.

PMID- 14722499
TI  - Childhood cervical lymphadenopathy.
AB  - Cervical lymphadenopathy is a common problem in children. The condition most
      commonly represents a transient response to a benign local or generalized
      infection, but occasionally it might herald the presence of a more serious
      disorder. Acute bilateral cervical lymphadenopathy usually is caused by a viral
      upper respiratory tract infection or streptococcal pharyngitis. Acute unilateral
      cervical lymphadenitis is caused by streptococcal or staphylococcal infection in
      40% to 80% of cases. The most common causes of subacute or chronic lymphadenitis
      are cat scratch disease, mycobacterial infection, and toxoplasmosis.
      Supraclavicular or posterior cervical lymphadenopathy carries a much higher risk
      for malignancies than does anterior cervical lymphadenopathy. Generalized
      lymphadenopathy is often caused by a viral infection, and less frequently by
      malignancies, collagen vascular diseases, and medications. Laboratory tests are
      not necessary in the majority of children with cervical lymphadenopathy. Most
      cases of lymphadenopathy are self-limited and require no treatment. The treatment
      of acute bacterial cervical lymphadenitis without a known primary source should
      provide adequate coverage for both Staphylococcus aureus and group A beta
      hemolytic streptococci.

PMID- 14722500
TI  - Breastfeeding knowledge and practice of pediatric nurse practitioners.
AB  - INTRODUCTION: The purpose of this secondary analysis is to examine and report on
      pediatric nurse practitioners' (PNPs') attitudes, experience, and knowledge about
      breastfeeding and to compare the results with those from a sample of
      pediatricians and other nurse practitioners and nurse-midwives. METHOD: A
      breastfeeding study questionnaire was sent to all PNPs (N = 95) in a northwestern
      state. The response rate was 81%. RESULTS: Respondents were nearly unanimous in
      their belief that "breast is best" and that it was their role to recommend
      breastfeeding to expectant mothers. In general, 74% of respondents believed they
      were effective or very effective in meeting the needs of breastfeeding patients.
      Although they were very supportive of breastfeeding, they were less knowledgeable
      about specific management strategies. Personal experience (nearly three fourths
      had themselves breastfed) was named by many as the most valuable source of
      information. Although PNPs appeared to have a more supportive attitude and better
      information than pediatric physicians, they reported themselves to be less
      effective in providing breastfeeding assistance than did their pediatric
      physician colleagues. DISCUSSION: PNPs generally agreed about the importance of
      promoting breastfeeding and their effectiveness in doing so. However, many PNPs
      did not gain experience in breastfeeding support and management in their
      educational programs and incorrectly answered questions on basic management
      strategies.

PMID- 14722501
TI  - Juvenile animal abuse: Practice and policy implications for PNPs.
AB  - Animal abuse has long been recognized as a sign of family violence and a warning
      sign of future aggression in children and adolescents. As leaders in youth
      violence prevention, pediatric nurse practitioners need to be aware of the
      prevalence and types of juvenile animal cruelty and its relationship to human
      violence. In doing so, they can champion for health care and related policies for
      this disturbing problem, described by Ascione as an underreported and
      understudied issue that may add to the understanding and prevention of youth
      violence."[One of the most dangerous things that can happen to a child] is when
      the child who kills or tortures [an animal] is not caught, or if caught is not
      punished." -Anthropologist Margaret Mead

PMID- 14722502
TI  - Ethnicity, traditional health beliefs, and health-seeking behavior: guardians'
      attitudes regarding their children's medical treatment.
AB  - INTRODUCTION: The purpose of this research was to examine ethnic variation in
      attitudes about traditional health beliefs concerning the use of home remedies
      and self-medicating behavior among guardians for their children. METHOD: As part
      of a community health care utilization study of children, questions were included
      regarding guardians' traditional health beliefs. Survey questions were adapted
      from the National Health Interview Survey or developed by the researchers. A
      cross-sectional stratified sample of households with children (n = 1606) were
      surveyed by random digit dialing. RESULTS: Two of four traditional health belief
      questions were significantly associated with ethnicity. Differences were observed
      for (a) guardians' willingness to treat their children with home remedies rather
      than use a health care provider if the condition was nonemergent and (b) their
      belief that some home remedies are better than prescribed drugs for curing
      illness (P <.01). DISCUSSION: Some traditional health beliefs among guardians
      differed by ethnicity. However, differences between the two minority groups were
      as pronounced as differences between minority and nonminority guardians. An
      understanding of the diversity of ethnic attitudes about traditional health
      beliefs is necessary for those involved in the delivery of health care. A
      stereotypical view that larger proportions of minorities subscribe to traditional
      health beliefs than do Whites is not supported in this research.

PMID- 14722503
TI  - Pediatric cystic fibrosis: evaluating costs and genetic testing.
AB  - The purpose of this article is to present a systematic, critical review of
      literature and data sources pertaining to pediatric cystic fibrosis, emphasizing
      and evaluating factors of costs and genetic testing. Cystic fibrosis is the most
      common fatal genetic disease in the United States. Therefore, its cause,
      prevalence, cost, and prevention make it important for review. Furthermore, the
      recent National Institutes of Health Consensus Statement on Genetic Testing for
      Cystic Fibrosis, the laboratory standards and guidelines published by the
      American College of Medical Genetics, the American College of Obstetricians and
      Gynecologists, and the National Human Genome Research Institute, and the
      increasing interest in genetic testing make it timely to discuss this major
      pediatric health topic. A broad educational effort, particularly among health
      care professionals, and genetic screening are advocated.

PMID- 14722504
TI  - Evaluation and management of obesity in children and adolescents.

PMID- 14722505
TI  - When will I start my periods?

PMID- 14722506
TI  - Preconception education: caring for the future.

PMID- 14722507
TI  - Developing a successful poster presentation.

PMID- 14722508
TI  - Choosing an infant or pediatric formula.

PMID- 14722509
TI  - A historical perspective on the changing contours of medical residency programs.

PMID- 14722510
TI  - Children's inhumanity to children.

PMID- 14722511
TI  - Polycystic ovary syndrome: what is it and how should we treat it?

PMID- 14722512
TI  - Clinical and research aspects of ambulatory blood pressure monitoring in
      children.

PMID- 14722513
TI  - Bullying behavior and associations with psychosomatic complaints and depression
      in victims.
AB  - OBJECTIVES: To assess the association between bullying behavior and a wide
      variety of psychosomatic health complaints and depression. Study design In a
      cross-sectional study, 2766 elementary school children age 9 to 12 years filled
      out a questionnaire on bullying behavior and health complaints. Three groups
      bullied children, active bullies, and children who both bully and are bullied
      were compared with the group of children not involved in bullying behavior.
      Subsequently, risks for psychosomatic symptoms and depression were calculated by
      means of odds ratios. RESULTS: Bully victims had significantly higher chances for
      depression and psychosomatic symptoms compared with children not involved in
      bullying behavior. Odds ratios were as follows: headache, 3.0; sleeping problems,
      2.4; abdominal pain, 3.2; bed-wetting, 2.9; feeling tired, 3.4; and depression,
      7.7. Children who actively bullied did not have a higher chance for most of the
      investigated health symptoms. CONCLUSIONS: Being bullied is strongly associated
      with a wide range of psychosomatic symptoms and depression. These associations
      are similar to the complaints known to be associated with child abuse. Therefore,
      when such health complaints are presented, pediatricians and other health care
      workers should also be aware of the possibility that a child is being bullied to
      take preventive measures.

PMID- 14722514
TI  - Insulin sensitization early after menarche prevents progression from precocious
      pubarche to polycystic ovary syndrome.
AB  - OBJECTIVE: Girls with low birth weight (LBW) and with a history of precocious
      pubarche in childhood (PP) are at high risk of polycystic ovary syndrome (PCOS)
      in adolescence. In formerly LBW-PP girls, we examined whether initiation of
      insulin sensitization therapy early after menarche could prevent progression of
      PCOS features. Study design Twenty-four girls, small at term birth (mean weight,
      2.4 kg), who presented with PP (at mean age 6.7 years) and were currently (mean
      age, 12.4 years) postmenarcheal, with hyperinsulinemic hyperandrogenemia but
      nonobese, were randomly assigned to receive metformin (850 mg/d) or no treatment
      for 12 months. Six-month fasting blood samples were collected, and body
      composition was assessed by dual-energy x-ray absorptiometry. In addition,
      overnight growth hormone (GH) and gonadotropin secretion was analyzed in 10 girls
      (6 treated; 4 untreated) at 0 and 6 months. RESULTS: At baseline, compared with
      healthy control subjects, LBW-PP girls had dyslipidemia, excess truncal fat,
      reduced lean body mass, and increased insulin-like growth factor-I and GH levels.
      In untreated girls, insulin sensitivity, serum androgens, lipids, total and
      truncal fat mass, and lean body mass significantly diverged further from normal
      over 12 months. In metformin-treated girls, all these abnormalities significantly
      reversed within 6 months, and body composition continued to improve between 6 and
      12 months. CONCLUSIONS: Early metformin therapy prevents progression from PP to
      PCOS in a high-risk group of formerly LBW girls. This confirms the key role of
      hyperinsulinemic insulin resistance in the ontogeny of PCOS. Furthermore,
      normalization of body composition, lipid profiles, and GH secretion could reduce
      long-term cardiovascular risk.

PMID- 14722515
TI  - Ghrelin levels from fetal life through early adulthood: relationship with
      endocrine and metabolic and anthropometric measures.
AB  - OBJECTIVE: To establish mean plasma ghrelin levels during fetal life and
      childhood. Study design Cord blood was obtained at birth from premature (n=29)
      and full-term newborns (n=124). Fasting blood samples were taken from 224 normal
      subjects divided according to Tanner stage and sex. Ponderal index or body mass
      index was determined. Ghrelin; insulin-like growth factor (IGF)-I; IGF-II; IGF
      binding proteins 1, 2, and 3; insulin; glucose; and leptin levels were measured.
      RESULTS: Ghrelin levels did not differ between preterm and full-term newborns.
      Ghrelin increased significantly after birth, peaking during the first 2 years of
      life, then decreasing until the end of puberty. Ghrelin levels correlated
      negatively with anthropometric variables in full-term newborns and postnatally,
      but not in preterm newborns. A positive correlation between ghrelin and IGF
      binding protein 1 was found. CONCLUSIONS: Ghrelin changes significantly
      throughout development, correlating with anthropometric and metabolic parameters
      during extrauterine life. The highest levels of ghrelin are found during early
      postnatal life, when growth hormone begins to exert its effects on growth and
      important changes in food intake occur, suggesting that this hormone may
      participate in these processes.

PMID- 14722516
TI  - Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or
      recuperation.
AB  - OBJECTIVE: To study the influence of dietary intervention on plasma ghrelin
      levels in obese children and adolescents with anorexia nervosa (AN). Study design
      Prepubertal obese children (n=16) and 16 anorexic adolescents were studied at
      three different points: clinical diagnosis and after a reduction or recuperation
      of 25% and 50% of the initial BMI SD score. Controls included 21 Tanner growth
      stage 1 and 36 Tanner growth stage 5 subjects. We analyzed plasma ghrelin levels
      and their correlation with plasma levels of leptin, insulin, insulin-like growth
      factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1), insulin
      like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor
      binding protein 3 (IGFBP-3), and integrated concentration of growth hormone
      (ICGH) before and after dietary intervention. RESULTS: At diagnosis, ghrelin
      levels were significantly decreased in obese children (52% of control levels) and
      significantly increased in adolescents with AN (164% of control levels). After
      dietary intervention, ghrelin increased in obese patients but without reaching
      control levels even after a 50% reduction in body mass index (BMI). In
      adolescents with AN, ghrelin levels normalized after a 25% increase in BMI.
      Ghrelin correlated negatively with the BMI and positively with IGFBP-1 levels in
      controls but not in obese patients or in patients with AN at diagnosis. The
      positive correlation between ghrelin and IGFBP-1 was recovered after dietary
      intervention. CONCLUSIONS: Plasma ghrelin levels present opposite changes in
      obesity and AN after dietary intervention, suggesting that ghrelin is a good
      marker of nutritional status.

PMID- 14722517
TI  - Antenatal presentation of biliary atresia.
AB  - OBJECTIVES: To investigate the incidence, presence of associated anomalies, type
      of malformation, and natural history of children with biliary atresia (BA) who
      presented antenatally. Study design The database of 194 infants diagnosed with BA
      at our tertiary referral unit between 1991 and 2002 was reviewed for infants in
      whom routine antenatal ultrasound had revealed biliary cystic malformations
      (BCMs). A retrospective analysis of their medical records was undertaken.
      RESULTS: Nine infants (six girls) with BCM were identified (4.6% of total
      referred patients with BA); all were born after 37 weeks' gestational age and
      presented to us at a median age of 4 weeks (range, 1-14 weeks). The presence of
      the BCM was confirmed on postnatal ultrasonography. Median age at corrective
      surgery was 5 weeks (range, 2-16 weeks). At surgery, six patients had type III
      BA, including one with the biliary atresia-splenic malformation syndrome; two had
      type II BA; and one had type I BA. Postoperatively, the infants were followed for
      a median of 2 years (range, 6 months to 11 years). All infants successfully
      cleared their jaundice. CONCLUSIONS: Improved techniques in routine antenatal
      ultrasonography can allow early recognition of BCM. This study suggests that BCM
      noted antenatally may represent early presentation of both biliary atresia
      splenic malformation and nonsyndromic BA.

PMID- 14722518
TI  - Validation of surrogate estimates of insulin sensitivity and insulin secretion in
      children and adolescents.
AB  - OBJECTIVES: To compare insulin sensitivity and pancreatic beta-cell function
      measured by the euglycemic and the hyperglycemic clamp, with simple estimates of
      insulin sensitivity and pancreatic beta-cell function in youth. Study design We
      measured insulin sensitivity with a euglycemic clamp and first- and second-phase
      insulin secretion with a hyperglycemic clamp in 156 AA and white youths.
      Estimates of insulin sensitivity (fasting insulin level [I(F)], the ratio of
      fasting glucose [G(F)] to I(F) [G(F)/I(F)], homeostasis model assessment estimate
      of insulin sensitivity [HOMA IS], and quantitative insulin sensitivity check
      index [QUICKI]) and estimates of pancreatic beta-cell function (I(F), the ratio
      of I(F) to G(F) [I(F)/G(F)], and homeostasis model assessment estimate of
      pancreatic beta-cell function [HOMA %B]) were derived from fasting measurements.
      RESULTS: In the total group, IS(Eu) correlated strongly with I(F) (r=-0.92),
      G(F)/I(F) (r=0.92), HOMA IS (r=0.91), and QUICKI (r=0.91) (P<.01). First-phase
      and second-phase insulin secretion correlated with I(F), I(F)/G(F), and HOMA %B
      (first-phase insulin secretion: r=0.76, 0.79, 0.82; second-phase insulin
      secretion: r=0.83, 0.86, 0.86, respectively; P<.01). CONCLUSIONS: Simple
      estimates of insulin sensitivity and pancreatic beta-cell function using fasting
      insulin and glucose levels serve as surrogate measures of insulin sensitivity and
      secretion in nondiabetic youths. The validity of these conclusions in children
      with impaired glucose tolerance and type 2 diabetes mellitus remains to be
      determined.

PMID- 14722519
TI  - Alterations in bone characteristics associated with glycemic control in
      adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVE: To determine whether bone characteristics in adolescents with type 1
      diabetes mellitus (DM) are influenced by blood glucose regulation and disease
      duration. The subjects were adolescents with type 1 DM (n=55) recruited from the
      University of Utah's Primary Children's Pediatric Diabetes Treatment Center. A
      reference database consisting of 95 healthy adolescents from the same geographic
      area was used for comparison.Study design Measurements of the tibia by peripheral
      quantitative computed tomography were made to assess cortical and trabecular bone
      characteristics. Hip, spine, and whole body characteristics were measured by dual
      energy x-ray absorptiometry. Height, weight, health histories, Tanner stage,
      disease duration, insulin regimen, and glycosylated hemoglobin values were
      recorded. RESULTS: Age, maturation, and body size and composition values were
      similar between the subjects with type 1 DM and reference. Subjects with type 1
      DM had lower tibia trabecular and femoral neck density and whole body mineral
      content and density. The mean glycosylated hemoglobin value was inversely related
      to tibia trabecular bone density (R(2)=-0.30) and whole body bone mineral content
      (R(2)=-0.25) and accounted for 3.0% to 8.9% of the variance. CONCLUSIONS: Altered
      bone mineral acquisition in adolescents with type 1 DM may limit peak bone mass
      acquisition and increase the risk of osteoporosis in later life.

PMID- 14722520
TI  - Growth hormone treatment in children with familial dysautonomia.
AB  - OBJECTIVE: To assess experience with growth hormone (GH) therapy in patients with
      familial dysautonomia (FD). Study design Of 580 patients with FD registered at
      the Dysautonomia Center at New York University Medical Center, 13 patients (8
      males, 5 females) aged 1.10 to 15.10 years received GH treatment. GH doses ranged
      from 0.2 to 0.3 mg/kg/wk; one patient received 0.14 mg/kg/wk. Information
      regarding auxologic data, skeletal age, pubertal status, and spinal deformity
      before and after GH therapy was obtained from center records and treating
      endocrinologists. Growth velocity was analyzed before and during GH treatment at
      0 to 6 months, 6 to 12 months, 1 to 2 years, and >2 years. RESULTS: Before GH
      therapy, growth velocity was <5 cm/y in 10 patients and 5 to 6 cm/y in three
      patients. In the first six months of GH therapy, growth velocity exceeded
      pretreatment rates in all but one patient; 10 patients achieved an annualized
      growth rate >7 cm/y. Six of nine patients treated for more than one year grew >5
      cm/y. Less than optimal treatment responses were attributed to poor compliance,
      intercurrent illness, scoliosis, or advanced puberty. CONCLUSION: The data
      demonstrate that GH treatment in patients with FD may increase growth velocity,
      at least in the short term. This experiential data supports a future prospective
      study.

PMID- 14722521
TI  - Reduction in pediatric hospitalizations for varicella-related invasive group A
      streptococcal infections in the varicella vaccine era.
AB  - OBJECTIVES: To assess changes in hospitalization rates for invasive group A
      streptococcal (IGAS) and varicella-associated IGAS (VA-IGAS) infections at a
      pediatric hospital over a period of 9 years, to characterize clinical features of
      patients with IGAS infections, and to assess frequency of macrolide-resistant
      IGAS isolates. Study design Medical records of all hospitalized patients with
      group A streptococcus isolated from a normally sterile site from 1993 to 2001
      were reviewed. Data collected included demographics, clinical course,
      microbiologic features, outcome, and presence of streptococcal toxic shock
      syndrome (STSS) or necrotizing fasciitis (NF). Annual hospitalization rates for
      IGAS were determined. RESULTS: There were 144 patients with IGAS infections,
      including 11 (8%) with STSS or NF. Overall mortality rate was 2% (3/144) but 18%
      (2/11) among patients with STSS or NF. Preexisting varicella was present in 16%
      (23/144); 4 of 23 VA-IGAS cases had STSS or NF. Although there was no change in
      annual hospitalization rates for IGAS infections during the study period, the
      percentage of VA-IGAS hospitalizations decreased from 27% in the prevaccine era
      (1993 to 1995), to 16% during vaccine implementation (1996 to 1998) and 2% during
      widespread vaccine use (1999 to 2001) (linear-by-linear association, P=.001).
      Macrolide resistance was low in 1993 to 1995 (5%, 1/19) and 1996 to 1998 (0%,
      0/42) among tested IGAS isolates and increased significantly in 1999 to 2001
      (13%, 5/38) (Fisher exact, P=.035). CONCLUSIONS: A decline in pediatric varicella
      related IGAS hospitalizations was temporally associated with utilization of
      varicella vaccine. These data reinforce the importance of universal varicella
      vaccination for children. Increasing macrolide resistance among IGAS isolates
      indicates a need for continued surveillance.

PMID- 14722522
TI  - Effects of antenatal steroids on protein metabolism in preterm infants on the
      first day of life.
AB  - OBJECTIVE: To analyze, in an existing cohort of infants, whether antenatal
      administered corticosteroids influence protein metabolism in preterm infants on
      the first day of life. Study design Three groups of infants were studied. The
      mothers of 25 infants had received 2 or more doses of corticosteroids, the
      mothers of 5 had received 1 dose, and there was no antenatal steroid exposure for
      8 infants. Within a few hours after birth, a double-tracer leucine infusion was
      started by intravenous and intragastric routes and continued for 5 hours while
      the infants received only intravenous glucose. RESULTS: The plasma alpha-keto
      isocaproic acid (KIC) enrichment (mol percent excess, MPE) from the intravenous
      tracer was not different between infants who reveived no antenatal steroids
      (8.58+/-1.64), 1 dose (7.60+/-0.78), and 2 or more doses (7.61+/-1.29). From the
      intragastric tracer, the plasma KIC enrichment from the intragastric tracer was
      different among the 3 groups, 7.62+/-2.35 for 0 doses, 5.78+/-0.85 for 1 dose,
      and 5.53+/-1.58 for 2 or more doses of antenatal steroids. Plasma KIC enrichment
      from the intravenous tracer was significantly higher than from the intragastric
      tracer in infants who received antenatal steroids, whereas there was no
      difference in infants who had not received antenatal steroids. Plasma leucine
      enrichment showed the same results. CONCLUSIONS: Antenatal corticosteroid
      administration to the fetus has no effect on whole-body leucine metabolism on the
      first day of life. However, it is associated with an increase in splanchnic
      leucine uptake at birth.

PMID- 14722523
TI  - Mitochondrial DNA abnormalities and autistic spectrum disorders.
AB  - OBJECTIVES: To further characterize mtDNA defects associated with autistic
      features, especially the A3243G mtDNA mutation and mtDNA depletion.Study design
      Five patients with autistic spectrum disorders and family histories of
      mitochondrial DNA diseases were studied. We performed mtDNA analysis in all
      patients and magnetic resonance spectroscopy in three. RESULTS: Three patients
      manifested isolated autistic spectrum features and two had additional neurologic
      symptoms. Two patients harbored the A3243G mutation. In two others, the A3243G
      mutation was not found in accessible tissues but was present in tissues from
      their mothers. The fifth patient had 72% mtDNA depletion in skeletal muscle.
      CONCLUSIONS: Autistic spectrum disorders with or without additional neurologic
      features can be early presentations of the A3243G mtDNA mutation and can be a
      prominent clinical manifestation of mtDNA depletion. Mitochondrial dysfunction
      should be considered in patients who have autistic features and associated
      neurologic findings or who have evidence of maternal inheritance.

PMID- 14722524
TI  - Outcomes from an interprovincial program of newborn open heart surgery.
AB  - OBJECTIVES: To determine 18-month neurodevelopmental outcome of survivors of
      complex open heart surgery at </=6 weeks of age through an interprovincial
      program and to explore preoperative, operative, and postoperative outcome
      predictors. Study design Of 85 children from this inception cohort (21%
      mortality), 67 18-month-old survivors received multidisciplinary assessment
      including the Bayley Scales of Infant Development-II. Cumulative risk for adverse
      outcome was determined through univariate and multivariate analyses. RESULTS:
      Survival of the 85 children included 23 of 23 after arterial switch, 16 of 26
      after Norwood, six of six after total anomalous pulmonary venous drainage repair,
      and 22 of 30 after miscellaneous repair. Outcomes were as follows: in-hospital
      death, 14 (16%); postdischarge death, four (5%); motor/sensory disability, three
      (4%); motor/mental delay (<70), 21 (25%); and intact survivors, 43 (50%). Cohort
      mental (84+/-17) and motor (80+/-22) scores were lower for those with chromosomal
      abnormalities, 67+/-16 and 61+/-17, respectively. Fifty-five percent of the
      outcome variance was explained by duration of preoperative ventilation, 18%;
      genetic anomaly, 5%; intraoperative variables, 18%; and postoperative variables,
      14%. CONCLUSIONS: Risk for adverse outcome is cumulative, with preoperative
      determinants contributing significantly to total variance. Potentially modifiable
      variables should be sought in an attempt to improve outcome.

PMID- 14722525
TI  - Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity.
AB  - OBJECTIVE: The autosomal-dominant form of the hyperimmunoglobulin E syndrome (AD
      HIES) has been described as a multisystem disorder including immune, skeletal,
      and dental abnormalities. Variants of AD-HIES are known but not well defined.
      METHODS: We evaluated 13 human immunodeficiency virus-seronegative patients from
      six consanguineous families with an autosomal-recessive form of
      hyperimmunoglobulin E syndrome (AR-HIES) and 68 of their relatives. RESULTS:
      Persons affected with AR-HIES presented with the classical immunologic findings
      of hyperimmunoglobulin E syndrome, including recurrent staphylococcal infections
      of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and
      hypereosinophilia. In addition, severe recurrent fungal and viral infections with
      molluscum contagiosum, herpes zoster, and herpes simplex were noted. Autoimmunity
      was seen in two patients. Central nervous system sequelae, including hemiplegia,
      ischemic infarction, and subarachnoid hemorrhages, were common and contributed to
      high mortality. Notably, patients with AR-HIES did not have skeletal or dental
      abnormalities and did not develop pneumatoceles, as seen in AD-HIES. In
      lymphocyte proliferation assays, patients' cells responded poorly to mitogens and
      failed to proliferate in response to antigens, despite the presence of normal
      numbers of lymphocyte subpopulations. CONCLUSION: The autosomal-recessive form of
      hyperimmunoglobulin E syndrome is a primary immunodeficiency with elevated
      immunoglobulin E, eosinophilia, vasculitis, autoimmunity, central nervous system
      symptoms, and high mortality. AR-HIES lacks several of the key findings of AD
      HIES and therefore represents a different, previously unrecognized disease
      entity.

PMID- 14722526
TI  - Histoplasmosis in a pediatric oncology center.
AB  - OBJECTIVE: To understand the presentation and current management of
      histoplasmosis in a pediatric oncology center. Study design Retrospective review
      of clinical features of patients with histoplasmosis at a tertiary-care cancer
      center in an endemic area. RESULTS: Between 1988 and 2001, 57 patients with
      cancer had 61 episodes of acute histoplasmosis. Of these, 76% were male, and 64%
      had acute lymphocytic leukemia (ALL). Most were not neutropenic and had
      nonspecific febrile illnesses. The most rapid and specific tests for
      histoplasmosis in patients with cancer were histopathologic examination of lung
      biopsy specimens in patients with localized pulmonary infection and Histoplasma
      sp. antigen detection in the urine of patients with disseminated histoplasmosis
      (DH). The mean times to diagnosis were 20.6+/-15.2 days (pulmonary) and 18.6+/
      8.2 days (disseminated) after the onset of symptoms. Most patients were treated
      with amphotericin B (AmB) followed by azole drugs for a mean of 8.5+/-3.1 weeks
      (pulmonary) and 10.4+/-7.9 weeks (disseminated). No patient died of
      histoplasmosis, but cancer therapy often was modified because of the infection.
      Most received unnecessary antibacterial drugs. CONCLUSIONS: Most readily
      available diagnostic tests for histoplasmosis lack sensitivity in these patients.
      Delay in diagnosis of histoplasmosis complicates care. No deaths were attributed
      to histoplasmosis; outcomes after treatment are good.

PMID- 14722527
TI  - Clinicopathologic conference: a large pulmonary cavitary lesion in a 2-year-old
      boy.

PMID- 14722528
TI  - Enzyme replacement therapy and monitoring for children with type 1 Gaucher
      disease: consensus recommendations.

PMID- 14722529
TI  - Posttraumatic stress disorder after dog bites in children.
AB  - Of 22 children who were victims of dog bite, 12 had symptoms of posttraumatic
      stress disorder 2 to 9 months after the bite. Violent dog attacks inflicting
      multiple and/or deep wounds were associated with risk of posttraumatic stress
      disorder.

PMID- 14722530
TI  - Hepatic fibrosis and survival in biliary atresia.
AB  - In biliary atresia, progression of hepatic fibrosis before the Kasai
      portoenterostomy may explain why age is a major determinant of survival of the
      native liver. Blinded fibrosis scoring of surgical liver biopsies demonstrated
      that age and fibrosis correlate. Those biopsies with severe fibrosis predicted
      significantly worse survival.

PMID- 14722531
TI  - Posthemorrhagic unilateral hydrocephalus: fenestration of septum pellucidum as an
      alternative to shunt implantation.
AB  - Unilateral hydrocephalus caused by occlusion of the foramen of Monro is rare. We
      report two cases in neonates caused by prenatal hemorrhage, their radiographic
      findings, and surgical treatment. With posthemorrhagic progressive unilateral
      hydrocephalus, early intervention with fenestration of septum pellucidum should
      be considered.

PMID- 14722532
TI  - Sudden death in growth hormone-treated children with Prader-Willi syndrome.
AB  - A 4-year-old boy with Prader-Willi syndrome died suddenly while asleep on day 67
      of growth hormone treatment. During treatment, snoring had worsened. Autopsy
      showed multifocal bronchopneumonia. This case and two others recently published
      suggest that growth hormone may be associated with obstructive apnea, respiratory
      infection, and sudden death in this condition.

PMID- 14722533
TI  - Successful hematopoietic stem cell transplantation in Farber disease.
AB  - Farber disease, a lysosomal storage disorder, has a dismal prognosis leading to
      death with progressive granulomatous inflammation, even in patients without
      central nervous system involvement (type 2/3). We report the first successful
      hematopoietic stem cell transplantations in 2 patients with Farber disease type
      2/3, resulting in resolution of symptoms.

PMID- 14722534
TI  - Hand it to the skin in Costello syndrome.

PMID- 14722535
TI  - Participation in randomized trials in developing countries.

PMID- 14722537
TI  - Measles vaccination in Canada.

PMID- 14722539
TI  - Prospective randomized controlled trial of argon plasma coagulation ablation vs.
      endoscopic surveillance of patients with Barrett's esophagus after antireflux
      surgery.
AB  - BACKGROUND: Argon plasma coagulation is one of several techniques used to ablate
      Barrett's esophagus. This study assessed the efficacy and safety of argon plasma
      coagulation in the ablation of Barrett's esophagus in patients who have undergone
      antireflux surgery. METHODS: A total of 40 patients with Barrett's esophagus who
      had undergone a fundoplication were entered into a prospective, randomized,
      unblinded study comparing argon plasma coagulation with endoscopic surveillance.
      Treatment was repeated until either no Barrett's epithelium remained or a maximum
      of 6 treatment sessions. RESULTS: One month after the final treatment, complete
      ablation was achieved in 12 patients. In the remaining 8, a reduction of over 95%
      was observed. One patient died at 9 months of an unrelated cause. At 1 year, one
      patient with residual Barrett's epithelium regressed completely, while relapse of
      Barrett's esophagus was seen in another because of fundoplication failure. Buried
      glands were observed in 35% patients at 1 month, but only 5% at 1 year. Dysplasia
      was never seen. In the surveillance group, partial regression was observed in 11
      patients, and, in 3 with short-segment Barrett's esophagus, regression was
      complete. The length of Barrett's esophagus increased in two patients. Two had
      low-grade dysplasia initially, but this was not evident at 1 year. Overall,
      complete ablation was achieved in 12 of 19 (63%) patients in the ablation group
      and 3 of 20 (15%) in the surveillance group (p<0.01). CONCLUSIONS: Argon plasma
      coagulation of Barrett's esophagus is safe and effective. The effects are
      durable, and buried glands may resolve with time. Long-term follow-up is required
      to assess the impact of argon plasma coagulation on cancer risk.

PMID- 14722540
TI  - Pancreatic stent insertion: consequences of failure and results of a modified
      technique to maximize success.
AB  - BACKGROUND: Increasingly, pancreatic stents are being placed to prevent post-ERCP
      pancreatitis. However, guidewire and stent placement may fail if the duct is
      small or tortuous, potentially exacerbating the risk. This study assessed the
      impact of unsuccessful pancreatic stent placement on complications and the
      efficacy of a modified technique for stent insertion when pancreatic ductal
      anatomy makes stent insertion technically difficult. METHODS: Technical variables
      and 30-day complications of consecutive therapeutic ERCPs, including attempted
      major papilla pancreatic stent insertion were prospectively studied. Success
      rates for pancreatic stent placement were compared for a 1-year period during
      which conventional deep guidewire insertion was used and another 1-year period in
      which a modified technique was used as needed in patients with ductal anatomy
      that made stent placement technically difficult. In the modified technique, a
      short (2-3 cm) small diameter (3F-5F) stent was placed over a 0.018-in nitinol
      tipped guidewire, passed as little as 1 to 2 cm beyond the pancreatic sphincter.
      RESULTS: In 225 high-risk therapeutic ERCPs, pancreatitis occurred after the
      procedure in two of 3 (66.7%) patients in whom pancreatic stent insertion failed
      vs. 32 of 222 (14.4%) patients with successful insertion (p=0.06). Severe
      pancreatitis occurred only after unsuccessful stent insertion. Significant
      multivariate risk factors for post-ERCP pancreatitis were unsuccessful pancreatic
      stent insertion (odds ratio 16.1: 95% CI[1.3, 200]), sphincter of Oddi
      dysfunction (odds ratio 3.2: 95% CI[1.4, 7.5]), and prior post-ERCP pancreatitis
      (odds ratio 3.2: 95% CI[1.4, 7.1]). The following were not risk factors:
      performance of pancreatic, biliary, or needle-knife pre-cut sphincterotomy;
      number of pancreatic contrast injections; and difficult cannulation. Stent
      placement was unsuccessful in 3 (3.2%) of 93 attempts during the 1-year period in
      which a conventional technique was used vs. none of 132 attempts in a subsequent
      year in which the modified technique was used. CONCLUSIONS: Failed attempts at
      pancreatic stent placement are associated with an extremely high risk of post
      ERCP pancreatitis. Success can be consistently achieved by use of a modified
      technique.

PMID- 14722541
TI  - Detection of intestinal metaplasia in distal esophagus and esophagogastric
      junction by enhanced-magnification endoscopy.
AB  - BACKGROUND: Standard videoendoscopy identifies columnar-lined esophagus but
      cannot distinguish intestinal metaplasia from other types of epithelium. Enhanced
      magnification endoscopy identifies different mucosal pit patterns. A preliminary
      study suggested that a type 3 pattern is associated with the presence of
      intestinal metaplasia. This study assesses the value of enhanced-magnification
      endoscopy for the detection of intestinal metaplasia in the distal esophagus and
      esophagogastric junction in patients undergoing diagnostic EGD. METHODS: Patients
      undergoing diagnostic endoscopy for upper-GI symptoms underwent enhanced
      magnification endoscopy after instillation of 1.5% acetic acid. The enhanced
      magnification endoscopy mucosal pattern was classified into 3 types: 1, normal
      pits; 2, slit-reticular pattern; and 3, gyrus-villous pattern. Preliminary
      studies indicated that the type 3 pattern was related to intestinal metaplasia.
      One to 6 biopsies were targeted to areas having a type 3 pattern in columnar
      appearing mucosa in the distal esophagus or esophagogastric junction. In the
      absence of type 3 pattern, one to 8 biopsies were targeted to areas with a type 2
      pattern in columnar-appearing mucosa in the distal esophagus or esophagogastric
      junction. RESULTS: The overall frequency of intestinal metaplasia in the
      esophagus and esophagogastric junction was 38.8% (26/67 patients). There was a
      good correlation between the type 3 pattern and intestinal metaplasia in targeted
      biopsy specimens (sensitivity 88.5%, specificity 90.2%, positive predictive value
      85.2%, negative predictive value 92.5%, overall accuracy 90.0%). CONCLUSIONS:
      Enhanced-magnification endoscopy is useful for detection of intestinal metaplasia
      in distal esophagus and esophagogastric junction.

PMID- 14722542
TI  - Randomized, double-blinded, placebo-controlled trial of intravenously
      administered hyoscine N-butyl bromide in patients undergoing colonoscopy with
      patient-controlled sedation.
AB  - BACKGROUND: A prospective, double-blinded, placebo-controlled randomized trial
      was conducted to investigate the effect of the antispasmodic hyoscine N-butyl
      bromide (Buscopan) during colonoscopy. METHODS: A total of 120 patients
      undergoing colonoscopy were randomized to receive either 40 mg of hyoscine N
      butyl bromide (n=60) or normal saline solution (n=60) intravenously as
      premedication. Colonoscopy was performed under patient-controlled sedation.
      Outcome measures included cecal intubation and total procedure time, demanded and
      administered doses of patient-controlled sedation, spasm score, pain score,
      endoscopist satisfaction score, patient willingness to repeat colonoscopy, and
      vital signs (blood pressure, pulse rate) during colonoscopy. RESULTS: Mean cecal
      intubation time in the hyoscine N-butyl bromide group was significantly longer
      than the control group (12.20 vs. 9.74 minutes; p=0.04; but correction for
      multiple testing of data removed this significance). The use of hyoscine N-butyl
      bromide was associated with a significantly lower endoscopist mean satisfaction
      score (6.47 vs. 7.30; p=0.04; but correction for multiple testing of data removed
      this significance), higher demanded and administered mean doses of patient
      controlled sedation (respectively, 34.80 and 7.25 vs. 24.20 and 5.87; p=0.045;
      p=0.04, respectively; but correction for multiple testing of data removed these
      findings of significance), fewer patients willing to repeat colonoscopy (60% vs.
      83.9%; p=0.005), and more hemodynamic instability (p<0.001) when compared with
      the control group. No significant difference was found in the total procedure
      time, spasm score, or pain score. CONCLUSIONS: Premedication with intravenously
      administered hyoscine N-butyl bromide impedes colonoscope insertion and causes
      greater patient discomfort, as well as hemodynamic instability.

PMID- 14722543
TI  - Efficacy and safety of endoscopic dilation of esophageal strictures in
      epidermolysis bullosa.
AB  - BACKGROUND: Epidermolysis bullosa is a rare genetically determined disorder of
      the stratified squamous epithelium. Patients with the most severe forms develop
      scarring of the esophagus after ingestion of food. This results in dysphagia,
      which severely compromises the ability to eat. Maintenance of adequate
      nutritional intake is a central aim, but the most appropriate method is unknown.
      METHODS: The results of endoscopic through-the-scope balloon dilation under
      propofol anesthesia in 53 patients with epidermolysis bullosa and esophageal
      strictures are reported. RESULTS: Seventy-five percent of patients had a single
      stricture (range 1 to 6 strictures), most often in the proximal esophagus (median
      20 cm from incisors). A total of 182 dilations were performed (median two per
      patient) over a median follow-up period of 3.5 years. For all but 3 patients,
      there was an improvement in the dysphagia score. There was a mean increase in
      weight after the procedure of 2.9 kg: 95% CI[2.0, 3.8]; p<0.001, over a median 29
      days. There was no significant post-procedure morbidity. CONCLUSIONS: Endoscopic
      balloon dilation is a safe and effective treatment for the esophageal strictures
      of epidermolysis bullosa. In the majority of patients, dilation relieves
      dysphagia and improves nutritional status.

PMID- 14722544
TI  - The learning curve for EUS-guided FNA of pancreatic cancer.
AB  - BACKGROUND: EUS-guided FNA is an effective and safe method for tissue diagnosis
      of pancreatic cancer. However, EUS-guided FNA is technically challenging and
      requires special training. The number of cases required to become proficient and
      the technical steps required to achieve proficiency are unknown. METHODS: The
      first 57 EUS-guided FNAs of pancreatic masses by a trained endosonographer were
      analyzed retrospectively. For 50 masses, the histopathologic diagnosis ultimately
      was cancer. The sensitivity for the EUS-guided FNA diagnosis of adenocarcinoma
      was compared in quintiles of 10 procedures. RESULTS: Sensitivity for the
      diagnosis of pancreatic cancer from first to last quintile were, respectively,
      50%, 40%, 70%, 90%, and 80%. There was a significant increase in sensitivity for
      the first 30 cases after improvement in specific technical skills: shortening of
      echoendoscope position, scrupulous maintenance of the US view of the needle tip
      at all times, swift jabbing punctures, sampling multiple areas of the mass in
      each pass, and performing more than 10 "jiggles" per needle pass. Sensitivity for
      the diagnosis of pancreatic cancer was greater than 80% for the last 20 of the 57
      cases, a level that was maintained for cases 51 through 80. CONCLUSIONS: The
      current American Society for Gastrointestinal Endoscopy guideline of 25
      supervised EUS-FNA procedures for the diagnosis of pancreatic adenocarcinoma is
      reasonable.

PMID- 14722545
TI  - Tele-endoscopy: a way to provide diagnostic quality for remote populations.
AB  - BACKGROUND: Flexible endoscopy plays an important role in digestive health.
      However, access to endoscopy is limited in many rural areas throughout the world.
      Training non-physician personal to perform diagnostic endoscopy and to transmit
      images to a central hospital, where experienced endoscopists can review the
      procedures, may improve digestive health for patients in remote areas. The aim of
      this study was to evaluate the diagnostic quality and accuracy of upper-GI tele
      endoscopy. METHODS: Fifty patients scheduled for EGD underwent upper-GI tele
      endoscopy. The procedures were observed simultaneously by the endoscopist and a
      gastroenterologist observing from a remote station connected by 4 integrated
      services digital network telephone lines. The interpretation of the findings by
      both were compared and concordance for diagnosis of major and minor lesions was
      analyzed. RESULTS: Tele-endoscopic image quality was adequate to support
      diagnosis of abnormal lesions by the remote observer. Technical issues included
      worsening image quality caused by mild pixelation during rapid endoscope movement
      and rare loss of the telephone lines. The endoscopist identified 47 different
      major and 44 minor findings in the 50 patients. The observer missed one major
      lesion (columnar-lined esophagus) because of suspected inflammation and described
      10 non-existing major lesions (sensitivity 98%: 95% CI[89%, 99%], specificity
      80%: 95% CI[66%, 90%]). Some of the differences were because of interobserver
      variability. CONCLUSIONS: Upper-GI tele-endoscopy by using telephone lines has
      good diagnostic quality and is highly sensitive with regard to major findings.
      The misinterpretation of certain findings (esophageal ring, gastric erosions) may
      be caused by interobserver variability. The data strongly suggest that
      endoscopist and observer see similar endoscopic views.

PMID- 14722546
TI  - Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet
      agents: analysis of 1657 cases.
AB  - BACKGROUND: Anticoagulants and antiplatelet agents commonly are used to treat
      patients with cardiovascular and cerebrovascular diseases. Data on the safety of
      the use of these drugs before colonoscopic polypectomy are scanty. METHODS: An
      audit was conducted for a 2-year period of consecutive patients undergoing
      colonoscopy and polypectomy. Patient demographics, site and size of polyps, and
      the use of anticoagulants and antiplatelet agents were documented from a hospital
      on-line database. Bleeding episodes were classified as immediate or delayed and
      were graded as mild, moderate, or severe. Risk factors associated with
      postendoscopy bleeding were analyzed by multivariate logistic regression
      analysis. RESULTS: A total of 5593 cases were reviewed. Polypectomy was performed
      in 1657 patients. There were 37 cases of polypectomy-associated bleeding (2.2%);
      bleeding was immediate in 32 and delayed in 5. Multivariate analysis showed that
      warfarin use, after adjustment for the effects of each of the other factors, was
      an independent risk factor for bleeding, with an odds ratio 13.37: 95% CI[4.10,
      43.65]. Age; the location and size of polyp; and the use of aspirin, non
      steroidal anti-inflammatory drugs, and other antiplatelet agents were not
      associated with a higher risk of polypectomy-associated bleeding. CONCLUSIONS:
      The use of antiplatelet agents during polypectomy was not associated with an
      increase in post-polypectomy bleeding. In contrast, treatment with warfarin
      should be discontinued, because this was associated with a significant increase
      in post-polypectomy bleeding.

PMID- 14722547
TI  - Detection of occult liver metastases during EUS for staging of malignancies.
AB  - BACKGROUND: EUS is commonly used in the staging of GI, thoracic, and other
      malignancies. Studies suggest EUS can detect occult liver metastases, but the
      frequency with which this occurs is unknown. METHODS: Records were reviewed for
      all patients seen during a 3-year period who underwent EUS of the upper-GI tract
      for staging of known or suspected malignancy. Patients were included if there was
      histopathologic evidence of malignancy, they had undergone noninvasive liver
      imaging within 6 weeks of EUS, and liver surveillance was specifically mentioned
      in the report of the EUS procedure. RESULTS: A total of 222 patients were
      included. Liver lesions were seen in 27 patients, 17 of whom had an abnormal
      noninvasive liver imaging test. EUS-guided FNA of the liver was performed in 21
      patients and was diagnostic of malignancy in 15 (6.8%), 5 of whom (2.3%) had
      normal noninvasive imaging. In 6 patients, the EUS-guided FNA result was benign.
      EUS missed liver lesions in 4 patients known to have abnormalities by other
      imaging modalities. CONCLUSIONS: EUS can detect occult liver metastases in
      patients in whom noninvasive hepatic imaging studies are normal, although the
      frequency at which such lesions are detected is low. Liver surveillance during
      EUS is worthwhile for patients in whom there is another indication for the
      procedure; but, at present, EUS should not replace traditional imaging
      modalities.

PMID- 14722548
TI  - Unsedated transnasal PEG placement.
AB  - BACKGROUND: By using a small-diameter endoscope, EGD can be performed
      transnasally in adults. A prospective study was conducted to evaluate the
      feasibility of transnasal PEG placement without conscious sedation. METHODS:
      Unsedated transnasal PEG was attempted in 23 patients by using a 5.9-mm-diameter
      videoendoscope. The indication for PEG insertion, success or failure, reason(s)
      for failure, and adverse effects of the procedure were recorded. During the first
      month, all patients were monitored by telephone contact for complications and to
      verify functionality of the PEG. RESULTS: Transnasal PEG insertion was successful
      in 21 (91%) patients. The cause for failure was the inability to transilluminate
      the abdominal wall. Complications included epistaxis (n=1), minor wound infection
      (n=1), and soiling around the stoma (n=1). Of the 21 patients in whom transnasal
      PEG placement was successful, all were alive, with a functional gastrostomy at
      the 1-month follow-up. CONCLUSIONS: Unsedated transnasal PEG tube insertion is
      minimally invasive, is feasible in daily practice in selected patients, and
      rarely is associated with complications.

PMID- 14722549
TI  - Endoscopic classification of Barrett's esophagus.

PMID- 14722550
TI  - Endoscopic ablative therapy for Barrett's esophagus: current status.

PMID- 14722551
TI  - EUS-guided FNA: the training is moving.

PMID- 14722552
TI  - Focal intestinal lymphangiectasia.

PMID- 14722553
TI  - Synovial sarcoma metastatic to stomach and duodenum.

PMID- 14722554
TI  - Pyloric Brunner's gland hamartoma.

PMID- 14722555
TI  - Minute pedunculated colon cancer with submucosal invasion.

PMID- 14722556
TI  - Clonorchiasis and biliary stones.

PMID- 14722557
TI  - Sigmoidorectal intussusception.

PMID- 14722558
TI  - Clinical applications of the argon plasma coagulator.

PMID- 14722559
TI  - Transgastric gastropexy and hiatal hernia repair for GERD under EUS control: a
      porcine model.
AB  - BACKGROUND: Endoluminal operations for gastroesophageal reflux currently are
      limited by the inability to visualize and manipulate structures outside the wall
      of the gut. This may be possible by using EUS. The aims of this study were the
      following: to define the EUS anatomy of structures outside the gut that influence
      reflux, to place stitches in the median arcuate ligament, to perform posterior
      gastropexy, and to test the feasibility of crural repair under EUS control in
      pigs. METHODS: In survival experiments in 22 pigs, by using a linear-array
      echoendoscope, the median arcuate ligament and part of the right crus were
      identified and punctured with a needle, which served as a carrier for a tag and
      thread. These were anchored into the muscle. An endoscopic sewing device was
      used, allowing stitches to be placed through a 2.8-mm accessory channel to any
      predetermined depth. New methods allowed knot tying and thread cutting through
      the 2.8-mm channel of the echoendoscope. RESULTS: Stitches were placed through
      the gastric wall into the median arcuate ligament, and one stitch was placed just
      beyond the wall of the lower esophageal sphincter. The stitches were tied
      together and locked against the gastric wall. Median lower esophageal sphincter
      pressure, determined manometrically, was 11 mm Hg before surgery and 21 mm Hg
      after stitch placement (p=0.0002). The length of the lower esophageal sphincter
      increased from a median of 2.8 cm before the procedure to 3.5 cm after the
      procedure. At the postmortem, the median force required to pull the tags out of
      the median arcuate ligament was 2.8 kg. CONCLUSIONS: This study demonstrates that
      transgastric gastroesophageal reflux surgery, by using stitching under EUS
      control, can significantly increase lower esophageal sphincter pressure in pigs.

PMID- 14722560
TI  - EUS-guided photodynamic therapy of the pancreas: a pilot study.
AB  - BACKGROUND: Photodynamic therapy of pancreatic cancer by using percutaneously
      placed light catheters has been reported. The feasibility and safety of EUS
      guided photodynamic therapy of the pancreas was studied in a porcine model.
      METHODS: After injection of porfimer sodium, a 19-gauge needle was inserted into
      the pancreas, the liver, the spleen, and the kidney under EUS guidance. A small
      diameter quartz optical fiber was passed through the EUS needle and used to
      illuminate the tissue with laser light. The tissue response to photodynamic
      therapy was examined. RESULTS: Localized tissue necrosis was achieved in all
      organs, without significant complication. There was no significant difference in
      inflammation induced by photodynamic therapy within the various organs.
      CONCLUSIONS: EUS-guided photodynamic therapy is a safe and simple technique that
      can induce small areas of focal tissue ablation within the liver, the pancreas,
      the kidney, and the spleen, and potentially could be used to treat a variety of
      benign and malignant conditions.

PMID- 14722561
TI  - EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report
      of 6 cases.
AB  - BACKGROUND: Only a few cases have been reported of EUS-guided drainage of
      obstructed pancreatic or bile ducts. An initial experience with EUS-guided
      rendezvous drainage after unsuccessful ERCP is reported. METHODS: EUS-guided
      transgastric or transduodenal needle puncture and guidewire placement through
      obstructed pancreatic (n=4) or bile (n=2) ducts was attempted in 6 patients.
      Efforts were made to advance the guidewire antegrade across the papilla or
      surgical anastomosis. If guidewire passage was successful, rendezvous ERCP with
      stent placement was performed immediately afterward. RESULTS: EUS-guided duct
      access and intraductal guidewire placement was accomplished in 5 of 6 cases, with
      successful traversal of the obstruction, and rendezvous ERCP, with stent
      placement in 3 of 6 cases (two biliary, one pancreatic). The procedure was
      clinically effective in all successful cases (two patients with malignant
      obstructive jaundice, one with relapsing pancreatitis after
      pancreaticoduodenectomy). There was one minor complication (transient fever) but
      no pancreatitis or duct leak after successful or unsuccessful procedures.
      CONCLUSIONS: EUS is a feasible technique for allowing rendezvous drainage of
      obstructed biliary or pancreatic ducts through native papillae or anastomoses
      after initially unsuccessful ERCP.

PMID- 14722562
TI  - An animal model study to clarify and investigate endoscopic tissue coagulation by
      using a new monopolar device.
AB  - BACKGROUND: The purpose of this study was to evaluate a new device for endoscopic
      monopolar electrocoagulation and to develop ablative techniques by using this new
      device. METHODS: The new device consists of an overtube with a wire mesh
      electrode in an oval opening in the distal end and a balloon at the distal end.
      High-frequency electrical current was applied in 5 animal (swine) esophagi by
      using this specially designed monopolar electrocoagulation device. A total of 32
      "lesions" were ablated by using blend electrosurgical waveforms for different
      time durations. The esophagi were then resected for histopathologic evaluation.
      RESULTS: Histopathologic study of the ablated lesions demonstrated that, by using
      the monopolar electrocoagulation device, different levels of degeneration of the
      mucosa and submucosa were achieved. The method for use of the device is fast and
      easy to apply. CONCLUSIONS: The ablative procedure with the new overtube device
      is minimally invasive, clearly feasible, and easy to apply. This new device
      potentially can be used in patients for tissue ablation.

PMID- 14722563
TI  - Percutaneous endoscopic colostomy in patients with chronic intestinal pseudo
      obstruction.
AB  - BACKGROUND: Percutaneous endoscopic colostomy was used successfully to treat 3
      patients with chronic intestinal pseudo-obstruction whose symptoms were not
      controlled by conservative measures. METHODS: Percutaneous endoscopic colostomy
      tubes were placed to allow intermittent decompression of the colon in response to
      the occurrence of symptoms. The technique and the equipment are the same as for
      PEG and are described herein. OBSERVATIONS: Symptom improvement was observed in 3
      patients, and, to date, surgery has been avoided for all. CONCLUSIONS:
      Percutaneous endoscopic colostomy is a safe and effective management option for
      selected patients with chronic intestinal pseudo-obstruction.

PMID- 14722564
TI  - Erosions in the second part of the duodenum in patients with villous atrophy.
AB  - BACKGROUND: There are various, well-documented, duodenal endoscopic markers
      caused by the villous atrophy of celiac disease. Another abnormality seen in
      association with villous atrophy, erosions in the second part of the duodenum, is
      described. To our knowledge, this finding has not been heretofore described in
      patients with celiac disease. METHODS: Five patients with celiac disease and
      erosions were encountered over a period of 2 years. OBSERVATIONS: The erosions
      were multiple, superficial, and present in the second part of the duodenum but
      not the duodenal bulb. All 5 patients had findings typical of celiac disease
      (iron deficiency, osteopenia/osteoporosis), and 4 had at least one other
      endoscopic marker: scalloped duodenal folds (3), fold loss (2), or mosaic pattern
      mucosa (2). These patients represented 7% of new cases of celiac disease during
      the same time period. This pattern of erosion was not observed in over 1200 other
      patients undergoing upper endoscopy during the study period. CONCLUSIONS: In a
      European population, the finding of erosions confined to the second part of the
      duodenum is specific for villous atrophy, although sensitivity is low. Erosions
      in the second part of the duodenum should be added to the list of endoscopic
      markers of celiac disease.

PMID- 14722565
TI  - Efficacy of ERCP via the accessory papilla in children with choledochal cysts.
AB  - BACKGROUND: ERCP via the major duodenal papilla in children with choledochal cyst
      may not clearly visualize the entire pancreatic duct and the junction of the
      pancreatic and biliary ducts. This may be caused by obstruction of the pancreatic
      duct by a dilated common bile duct. METHODS: Patients with choledochal cysts who
      underwent ERCP with injection of contrast medium at the major duodenal papilla
      were classified as either belonging to a MP group, in which the entire pancreatic
      duct and junction of the pancreatic and biliary ducts were visualized, or to a
      M/AP group, in which these structures were either partially visualized or not
      visualized. ERCP via the accessory papilla subsequently was performed in the M/AP
      group by using 0.6- or 0.8-mm metal-tip catheters. The efficacy of ERCP via the
      accessory papilla in children with choledochal cysts was evaluated. OBSERVATIONS:
      ERCP was performed in 13 patients. Seven were assigned to the MP group and 6 to
      the M/AP group. ERCP via the accessory papilla in the M/AP group was successful
      in 5 of the 6 patients; pancreas divisum was demonstrated in one, a protein plug
      at the main pancreatic duct in another, and the entire pancreatic duct and
      junction of the pancreatic and biliary ducts in the remaining 3 patients. No
      patient developed pancreatitis as a result of ERCP, including ERCP via the
      accessory papilla. CONCLUSIONS: In children with choledochal cyst, ERCP via the
      accessory papilla is an effective method for visualization of the detailed
      structure of the entire pancreatic ductal system and junction of the pancreatic
      and biliary ducts when ERCP via the major duodenal papilla is unsuccessful.

PMID- 14722566
TI  - Cerebral artery air embolism during endoscopic variceal ligation: case report.

PMID- 14722567
TI  - Massive small bowel bleeding in a patient with amyloidosis.

PMID- 14722568
TI  - Endoscopic resection of a large leiomyoma of the esophagus.

PMID- 14722569
TI  - EUS-guided methylene blue pancreatography for minor papilla localization after
      unsuccessful ERCP.

PMID- 14722570
TI  - Synchronous primary pancreatic endocrine neoplasm and adrenal pheochromocytoma
      diagnosed by EUS-guided FNA.

PMID- 14722571
TI  - Bile duct cysts in a patient with autosomal dominant polycystic kidney disease.

PMID- 14722572
TI  - Two cases of superficial cancer in Barrett's esophagus detected by
      chromoendoscopy with crystal violet.

PMID- 14722573
TI  - Bilateral temporomandibular joint dislocation after PEG tube placement.

PMID- 14722574
TI  - Pancreatic foreign body: Ingested toothpick as a cause of pancreatitis and
      hemorrhage.

PMID- 14722575
TI  - Pill-induced esophagitis complicated by multiple esophageal septa.

PMID- 14722576
TI  - Esophageal stenosis, a rare complication of coin ingestion: Case report.

PMID- 14722577
TI  - Laparoscopic resection of a mesenteric cyst.

PMID- 14722578
TI  - Balloon-occluded retrograde transvenous obliteration as adjunctive treatment for
      gastric fundal varices: case report.

PMID- 14722579
TI  - Genetic and environmental sources of egg size variation in the butterfly Bicyclus
      anynana.
AB  - By dividing families of the tropical butterfly, Bicyclus anynana, among different
      larval (including early pupal) and adult (including late pupal) temperatures, we
      investigate the genetic and environmental effects on egg size. Both sources of
      variation affected egg size to similar extents. As previously found in other
      arthropods, egg size tended to increase at lower temperatures. Our data suggest
      that the plastic response in egg size can be induced during the pupal stage.
      Females reared as larvae at the same high temperature tended to lay larger eggs
      when transferred to a lower temperature, either as prepupae or pupae, compared to
      those remaining at the high temperature. Additionally, females reared as larvae
      at different temperatures, but maintained at the same temperature from the early
      pupal stage onwards, laid larger eggs after larval growth at a low temperature.
      Heritability estimates for egg size were about 0.4 (parent-offspring regression)
      and 0.2 (variance component estimates using the full-sib families). Although
      there seemed to be some variation in the plastic response to temperature among
      families, genotype-environment interactions were nonsignificant.

PMID- 14722580
TI  - Two-generation analysis of pollen flow across a landscape V: a stepwise approach
      for extracting factors contributing to pollen structure.
AB  - Patterns of pollen dispersal are central to both the ecology and evolution of
      plant populations. However, the mechanisms controlling either the dispersal
      process itself or our estimation of that process may be influenced by site
      specific factors such as local forest structure and nonuniform adult genetic
      structure. Here, we present an extension of the AMOVA model applied to the
      recently developed TWOGENER analysis of pollen pool structure. This model, dubbed
      the Stepwise AMOVA (StAMOVA), focuses on determining to what extent ecological,
      demographic, and/or environmental factors influence the observed genetic
      variation in spatially separated pollen pools. The analysis is verified for
      efficacy, using an extensive battery of simulations, illustrating: (1) how
      nonuniform adult genetic structure influences the differentiation of spatially
      separated pollen pools, and (2) how effectively the Stepwise analysis performs in
      carrying out the appropriate corrections. Finally, the model is applied to a
      Quercus alba data set, from which we have prior evidence that the adult genetic
      structure is nonuniformly distributed across the sampling landscape. From this
      data set, we show how the Stepwise model can be applied to remove the effects of
      spatial adult genetic structure on pollen pool differentiation and contrast these
      results with those derived from the original TWOGENER analysis.

PMID- 14722581
TI  - Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus:
      genetic arguments for a particular pathophysiological entity.
AB  - Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important
      cause of sudden death. Familial cases could account for 20% of all cases. A
      genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci
      (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study
      of a single family composed of 179 members with an abnormally high occurrence of
      TAA/AD disease. A total of 40 subjects from three generations were investigated.
      In addition to five cases of stroke and three cases of sudden death, there were
      four cases of AD and four cases of TAA in adults. In all, 11 cases of patent
      ductus arteriosus (PDA) were observed, two of which were associated with TAA and
      one with AD. Segregation analysis showed that the distribution of these vascular
      abnormalities was more likely compatible with a single genetic defect with an
      autosomal dominant pattern of inheritance. There were no clinical signs of
      Marfan, Elhers-Danlos vascular type or Char syndromes. Genetic linkage analysis
      was performed for seven genes or loci implicated in familial TAA/AD disease
      (COL3A1, FBN1, 3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-q24), Char syndrome
      (TFAP2B) or autosomal recessive PDA (12q24). Using different genetic models,
      linkage with these seven loci was excluded. Familial TAA/AD with PDA is likely to
      be a particular heritable vascular disorder, with an as yet undiscovered
      Mendelian genetic basis.

PMID- 14722582
TI  - Molecular characterization of an 11q14.3 microdeletion associated with
      leukodystrophy.
AB  - Leukodystrophies represent a heterogeneous group of rare hereditary diseases
      affecting the central nervous system. The underlying molecular defect remains
      unknown in almost 50% of cases. We previously assigned a new locus for
      leukodystrophy of unknown cause to chromosome 11q14.3 by identifying a de novo
      microdeletion in a sporadic case. We now report the precise molecular
      characterization of this microdeletion. Physical mapping of the region of
      interest allowed us to identify and analyze candidate gene(s) possibly implicated
      in leukodystrophy.

PMID- 14722583
TI  - Analysis of heavy neurofilament subunit gene polymorphism in Russian patients
      with sporadic motor neuron disease (MND).
AB  - Motor neuron disease (MND) results in the selective degeneration of motor neurons
      in the cerebral cortex, brain stem and spinal cord. The most common form of MND
      is amyotrophic lateral sclerosis (ALS). MND is complex and many genetic systems
      may be involved in the pathogenesis of this disease. Pathological and animal
      studies implicate neurofilament involvement in MND. The heavy subunit (NEFH) tail
      domain contains a repeated motif. In humans, there are two common variants: the
      45 motif repeats long allele (L) and 44 motif repeats short allele (S). Previous
      studies have shown that the NEFH tail may be involved in the pathogenesis of MND.
      To investigate whether the L/S genotypes of the NEFH gene are associated with
      MND, we studied the frequency of L and S alleles in sporadic MND patients and a
      control population from Moscow. We observed a difference in SS genotype frequency
      between the control population and sporadic MND patients from Moscow. It was
      established that the SS genotype is sufficiently higher in sporadic MND patients.
      Moreover, we determined that patients with the SS genotype have the highest value
      of loss of the total clinical score. In summary, we conclude that the NEFH gene
      is involved in the pathogenesis of sporadic MND. The SS genotype represents a
      risk factor for the development and progression of sporadic MND in the Moscow
      population.

PMID- 14722584
TI  - Association between COL1A1 gene polymorphisms and bone size in Caucasians.
AB  - Bone size is an important determinant of bone strength and a risk factor of
      osteoporotic fracture. Several studies indicate that bone size has a high
      heritability. Thus, a better understanding of genetic factors regulating bone
      size might have important clinical implications. In the present study, we
      examined the relationship between the collagen type I alpha 1 (COL1A1) gene and
      bone size at the spine, hip and wrist in a sample of 1873 subjects of Caucasian
      origin from 405 nuclear families. Three single-nucleotide polymorphisms (SNPs) in
      the COL1A1 gene were analyzed. The minor allele frequencies were 15.4, 18.8, and
      1.9% for SNP1, SNP2, and SNP3, respectively. Haplotypes were reconstructed based
      on the family information as well as marker genotypes using the program
      Genehunter. We did not find evidence of population stratification, within-family
      association, or linkage for either single SNPs or haplotypes at any skeletal
      site. Suggestive evidence of total association was observed for the wrist size at
      SNP2 (P=0.011). After adjusting age, sex, height, and weight, subjects with the T
      allele of SNP2 had, on average, 3.05% smaller wrist size than noncarriers. When
      the subjects were divided into families with only female offspring and families
      with male offspring only, similar total associations were found at the wrist size
      for SNP2 with P-values of 0.011 and 0.010, respectively. In conclusion, the
      COL1A1 gene may have some effects on bone size variation at the wrist, but not at
      the spine or hip in our Caucasian nuclear families.

PMID- 14722585
TI  - Advances in AAV-mediated gene transfer for the treatment of inherited disorders.
AB  - The holy grail of gene therapy is the cure of genetic diseases. To achieve this
      goal, a vector system is desirable that offers a high level of safety combined
      with clinical efficacy and versatility in terms of potential applications. Gene
      therapy vectors based on recombinant adeno-associated viruses (AAVs) meet all of
      these criteria: They are nonpathogenic, devoid of viral coding sequences, and
      mediate long-term gene expression in the absence of an immune or inflammatory
      response. Moreover, with the recent discovery of novel AAV serotypes, there is
      now one preferred serotype for nearly every organ or tissue to target. Thus, AAV
      gene therapy vectors are increasingly becoming the vectors of choice for the
      treatment of inherited disorders.

PMID- 14722586
TI  - MtDNA evidence for a genetic bottleneck in the early history of the Ashkenazi
      Jewish population.
AB  - The relative roles of natural selection and accentuated genetic drift as
      explanations for the high frequency of more than 20 Ashkenazi Jewish disease
      alleles remain controversial. To test for the effects of a maternal bottleneck on
      the Ashkenazi Jewish population, we performed an extensive analysis of
      mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS-1) sequence and
      restriction site polymorphisms in 565 Ashkenazi Jews from different parts of
      Europe. These patterns of variation were compared with those of five Near Eastern
      (n=327) and 10 host European (n=849) non-Jewish populations. Only four mtDNA
      haplogroups (Hgs) (defined on the basis of diagnostic coding region RFLPs and HVS
      1 sequence variants) account for approximately 70% of Ashkenazi mtDNA variation.
      While several Ashkenazi Jewish mtDNA Hgs appear to derive from the Near East,
      there is also evidence for a low level of introgression from host European non
      Jewish populations. HVS-1 sequence analysis revealed increased frequencies of
      Ashkenazi Jewish haplotypes that are rare or absent in other populations, and a
      reduced number of singletons in the Ashkenazi Jewish sample. These diversity
      patterns provide evidence for a prolonged period of low effective size in the
      history of the Ashkenazi population. The data best fit a model of an early
      bottleneck (approximately 100 generations ago), perhaps corresponding to initial
      migrations of ancestral Ashkenazim in the Near East or to Europe. A genetic
      bottleneck followed by the recent phenomenon of rapid population growth are
      likely to have produced the conditions that led to the high frequency of many
      genetic disease alleles in the Ashkenazi population.

PMID- 14722587
TI  - Fostering psychosocial wellness in oncology nurses: addressing burnout and social
      support in the workplace.
AB  - PURPOSE/OBJECTIVES: To identify psychosocial wellness and the avoidance of
      burnout as key priorities for the retention of oncology nurses and to describe a
      program designed for a specific setting to enhance the psychosocial wellness and
      coping skills of oncology nurses. DATA SOURCES: Published research, books, and
      journal articles; theory; practice; and personal experience. DATA SYNTHESIS:
      Oncology nurses benefit from programs designed to bolster the development of
      coping skills to reduce stress, foster supportive relationships in the workplace,
      facilitate work-related grief and bereavement, and reduce burnout. CONCLUSIONS:
      Fostering psychosocial wellness in the workplace potentially can increase
      oncology nurse retention. IMPLICATIONS FOR NURSING: A renewed recognition of the
      stressful nature of oncology nursing should give rise to programs that address
      the psychological well-being of oncology nurses. Oncology nursing leadership,
      recognizing the potential for stress and burnout inherent in this profession,
      should research and develop programs to enhance staff coping skills and mutual
      support.

PMID- 14722588
TI  - Describing a nurse case manager intervention to empower low-income men with
      prostate cancer.
AB  - PURPOSE/OBJECTIVES: Describe and categorize nurse case manager (NCM)
      interventions for low-income, uninsured men with prostate cancer. RESEARCH
      APPROACH: Descriptive, retrospective record review. SETTING: Statewide free
      prostate cancer treatment program in which each patient is assigned an NCM.
      PARTICIPANTS: 7 NCMs who developed interventions based on empowerment through
      increasing self-efficacy. METHODOLOGIC APPROACH: NCM entries were extracted and
      coded from 10 electronic patient records, line by line, to reveal initial themes.
      Themes were grouped under categories. Investigators then reviewed and expanded
      these categories and their descriptions and postulated linkages. Linkages and
      relationships among categories were empirically verified with the original data.
      NCM entries from another 20 records were prepared in the same manner as the
      original records. Modifications were made until the categories contained all of
      the data and no new categories emerged. Categories were verified for content
      validity with the NCMs and reviewed for completeness and representation. MAIN
      RESEARCH VARIABLES: NCM interventions. FINDINGS: Categories of NCM interventions
      emerged as assessment, coordination, advocacy, facilitation, teaching, support,
      collaborative problem solving, and keeping track. Categories overlapped and
      supported each other. NCMs tailored interventions by combining categories for
      each patient. CONCLUSIONS: The skillful tailoring and execution of intervention
      strategies depended on the knowledge, experience, and skill that each NCM brought
      to the clinical situation. NCM categories were consistent with the tenets of the
      self-efficacy theory. INTERPRETATION: The model, based on NCM interventions,
      provides a guide for the care of underserved men with prostate cancer. Components
      of the model need to be tested.

PMID- 14722589
TI  - An integrated approach to an analysis of symptom management in patients with
      cancer.
AB  - PURPOSE/OBJECTIVES: To provide a definition, describe uses, and identify
      essential attributes of symptom management by emphasizing the philosophical base
      for the concept. DATA SOURCES: 51 references (i.e., books and articles) published
      from 1980-2003 and located through the Ovid database. DATA SYNTHESIS: Symptoms
      are subjective and personal phenomena, incorporating the dimensions of symptom
      occurrence, symptom distress, and symptom experience. Symptom management has been
      conceptualized and described as self-activity. Symptom status is the direct
      outcome of symptom management, with symptom distress, quality of life, and
      performance as major indicators. CONCLUSIONS: The essential attributes of symptom
      management in patients with cancer are subjectivity, experientiality,
      intentionality, multidimensionality, dynamic process, and positive and negative
      outcomes. IMPLICATIONS FOR NURSING: Findings can help oncology nurses and other
      healthcare professionals to better understand the process of managing a symptom
      and the influential factors that affect positive outcomes. The information from
      this analysis can be used to design educational and interventional programs for
      symptom management. Future research is needed to establish interventions that
      relieve and decrease the distress from or prevent the occurrence of symptoms.

PMID- 14722590
TI  - The effects of an educational intervention on oncology nurses' attitude,
      perceived knowledge, and self-reported application of complementary therapies.
AB  - PURPOSE/OBJECTIVES: To evaluate the effects of an educational program on oncology
      nurses' attitude, perceived knowledge, and self-reported application of 10
      complementary therapies (art, exercise, humor, imagery, journaling, massage,
      music, relaxation, spirituality, and touch). DESIGN: Quasi-experimental with a
      pre- and post-test design. SETTING: A large tertiary care medical center in the
      midwestern United States. SAMPLE: A convenience sample consisting of 44 RNs
      working on two hematology and oncology patient care units. Eleven nurses
      comprised the educational intervention group, and 14 nurses on the same unit
      served as one control group. A second control group was comprised of 19 nurses
      from a different unit. METHODS: The study approach consisted of the assessment of
      all participants' initial attitude toward, knowledge of, and application of
      complementary therapies. A researcher-developed questionnaire was completed
      before and at three and six months after the educational intervention. MAIN
      RESEARCH VARIABLES: Nurses' attitudes toward, knowledge of, and use of
      complementary therapies. FINDINGS: Nurses value complementary therapies but lack
      the knowledge regarding their application. In addition, a gap exists between self
      reported knowledge and the actual application of therapies. An eight-hour
      educational intervention was useful in enhancing knowledge and, to some degree,
      increasing application of some of the therapies. According to participants, lack
      of time was the main deterrent impeding use of complementary therapies in their
      nursing practice. CONCLUSIONS: Education can affect the knowledge and integration
      of complementary therapies in nursing practice. IMPLICATIONS FOR NURSING: Further
      research is needed to evaluate outcomes and determine educational approaches that
      will produce positive changes in nurses' attitudes toward, knowledge of, and
      application of complementary therapies.

PMID- 14722591
TI  - Virtual reality as a distraction intervention for women receiving chemotherapy.
AB  - PURPOSE/OBJECTIVES: To explore the use of virtual reality as a distraction
      intervention to relieve symptom distress in women receiving chemotherapy for
      breast cancer. DESIGN: Crossover study. SETTING: The outpatient clinic of a
      midwestern comprehensive cancer center. SAMPLE: 20 women 18-55 years of age.
      METHODS: Using a crossover design, 20 subjects served as their own controls. For
      two matched chemotherapy treatments, one pretest and two post-test measures were
      employed. Participants were assigned randomly to receive the virtual reality
      distraction intervention during one chemotherapy treatment and received no
      distraction intervention (control condition) during an alternate chemotherapy
      treatment. An open-ended questionnaire elicited each subject's evaluation of the
      intervention. MAIN RESEARCH VARIABLES: Symptom distress, fatigue, anxiety.
      FINDINGS: Significant decreases in symptom distress and fatigue occurred
      immediately following chemotherapy treatments when women used the virtual reality
      intervention. CONCLUSIONS: The distraction intervention decreased symptom
      distress, was well received, and was easy to implement in the clinical setting.
      IMPLICATIONS FOR NURSING: Nursing interventions to manage chemotherapy-related
      symptom distress can improve patient quality of life and increase chances for
      survival by reducing treatment-related symptom distress and enhancing patients'
      ability to adhere to treatment regimens and cope with their disease.

PMID- 14722592
TI  - The effects of spirituality on well-being of people with lung cancer.
AB  - PURPOSE/OBJECTIVES: To examine the effects of spirituality on the sense of well
      being of people with lung cancer. DESIGN: Descriptive, correlational study.
      SETTING: Urban and rural oncology and radiation centers. SAMPLE: 60 adults
      ranging from 33-83 years of age. Most participants had non-small cell lung cancer
      and were female, Caucasian, and older than 50. METHODS: Participants completed a
      questionnaire composed of six survey instruments: Life Attitude Profile-Revised,
      Adapted Prayer Scale, Index of Well-Being, Symptom Distress Scale, a background
      information sheet, and a cancer characteristics questionnaire. Correlations among
      study concepts were examined, and multiple regression analysis was used to
      determine the effects of spirituality. MAIN RESEARCH VARIABLES: Meaning in life,
      prayer activities and experiences, symptom distress, and psychological well
      being. FINDINGS: Higher meaning in life scores were associated with higher
      psychological well-being and lower symptom distress scores. Higher prayer scores
      were associated with higher psychological well-being scores. Regression analysis
      indicated that meaning in life mediated the relationship between functional
      status and physical responses to lung cancer and explained 9% of the variance in
      symptom distress. Prayer mediated the relationship between current physical
      health and psychological responses and explained 10% of the variance in
      psychological well-being. CONCLUSIONS: Aspects of spirituality, meaning in life,
      and prayer have positive effects on psychological and physical responses in this
      group of people with lung cancer. IMPLICATIONS FOR NURSING: This research
      provides knowledge about spirituality and sense of well-being to guide the care
      of people with lung cancer.

PMID- 14722593
TI  - Post-breast cancer lymphedema: understanding women's knowledge of their
      condition.
AB  - PURPOSE/OBJECTIVES: To investigate chronic condition representations and
      treatment choices among women with post-breast cancer lymphedema (LE) to
      understand their receipt and use of accurate medical information. DESIGN:
      Qualitative, template analysis. SETTING: Midsized midwestern city and surrounding
      rural areas. SAMPLE: 18 Caucasian women aged 37-87 years (mean = 58.8 years) with
      LE. METHODS: Telephone and face-to-face interviews, lasting 45-60 minutes, were
      conducted by research students and graduate nursing students. Interviews were
      audiotaped, professionally transcribed, and verified for transcription accuracy.
      Self-regulation theory as a template was applied to (a) understand participants'
      use of health information to cope with LE and (b) evaluate the accuracy of
      participants' health information that may have influenced participants' abilities
      to make appropriate prevention or treatment choices. MAIN RESEARCH VARIABLES:
      Participants' illness representations and coping strategies. FINDINGS:
      Participants were aware of the fundamental cause of their LE--breast cancer
      treatment. They also were conscious of other causes of symptom onset. These
      causes are supported by existing empirical evidence. Participants' treatment
      choices were consistent (e.g., use of compression treatment, massage, elevation,
      pumps, therapists and therapy centers, and positive attitude and faith) and
      inconsistent (e.g., effectiveness of exercise and medication in management of LE)
      with empirical evidence. CONCLUSIONS: Future research and practice should target
      the role of exercise as a cause of LE and as a treatment option, investigate
      allergic reactions as a possible catalyst of LE symptoms, work to improve
      diagnosis of LE and patient education, and examine the effectiveness of
      medications as a treatment method. IMPLICATIONS FOR NURSING: Review of LE risk
      factors in the postoperative period and continued assessment and education are
      vital to a comprehensive approach to post-breast cancer LE care.

PMID- 14722594
TI  - An intervention to increase mammography use by Korean American women.
AB  - PURPOSE/OBJECTIVES: To test the effectiveness of a community-based intervention
      to increase mammography screening for Korean American women. DESIGN: Quasi
      experimental, pre-/post-test, three-group design. SETTING: Urban Korean American
      communities in Southern California. SAMPLE: 141 Korean American women, aged 40
      75, who had not had a mammogram in the previous 12 months. METHOD: Two Korean
      churches were selected randomly to be study sites that would provide health
      screening programs. The study included an experimental group that would have
      access to a peer-group educational program and low-cost mammography, a group that
      would have access to low-cost mammography alone, and a control group. Participant
      focused strategies were used to involve Korean American women from the community.
      MAIN RESEARCH VARIABLES: Mammography use, breast cancer screening attitudes, and
      knowledge. FINDINGS: Women in the experimental program had significantly improved
      attitudes and knowledge about breast cancer screening. Mammography use in the
      experimental group (87%) was not significantly different from that in the
      mammography-access-only group (72%). Both interventions proved to be more
      effective than no intervention at all (control group = 47%). CONCLUSIONS: An
      educational program that includes participant-focused research strategies and
      access to low-cost mammograms resulted in higher levels of screening.
      IMPLICATIONS FOR NURSING: Community-focused interventions can increase rates of
      cancer screening among Korean American women.

PMID- 14722595
TI  - Information and support needs of adolescent children of women with breast cancer.
AB  - PURPOSE/OBJECTIVES: To elicit detailed descriptions of adolescents' information
      and support needs in response to their mothers' breast cancer. DESIGN:
      Exploratory, qualitative. SETTING: Four different outpatient and inpatient
      oncology settings in western Canada. SAMPLE: 31 adolescent children of women in
      five illness phases. METHODS: 27 semistructured interviews and two focus groups
      were conducted. Interviews were audiotaped, transcribed, and analyzed using
      constant comparison techniques. The Communication Subscale of the McMaster Family
      Assessment Device also was administered to assess family communication patterns.
      FINDINGS: Information needs were sources of information, information content,
      degree of helpfulness, and information timing. Support needs were type, degree of
      helpfulness, form, and source. CONCLUSION: Most of the adolescents reported that
      their needs were poorly met. IMPLICATIONS FOR NURSING: Women with breast cancer
      have a need for family-focused care. Further research is required to develop
      interventions that can assist nurses in providing care that meets the needs of
      adolescent children and other family members of women with breast cancer.

PMID- 14722596
TI  - Implementation and refinement of a research utilization course for oncology
      nurses.
AB  - PURPOSE/OBJECTIVES: To describe the implementation and refinement of a yearly
      research utilization (RU) course for oncology nurses. DESIGN: Formative program
      evaluation. SAMPLE: 22 oncology nurses selected based on competitively reviewed
      project proposals. METHODS: The one-day RU course was held five times prior to
      the annual fall Oncology Nursing Society conference. The course consisted of
      brief didactic sessions on RU, project presentations by participants, faculty
      reviews, and discussions of practical issues related to project implementation.
      MAIN RESEARCH VARIABLES: Course content, usefulness of course components.
      FINDINGS: Based on immediate postcourse, 6-month, and 12-month feedback,
      refinements were made to the course. A major change (in year three) was the
      addition of a "preparation packet," which contained resources about RU and
      directed students to accomplish specific precourse goals, and access to a faculty
      mentor. Evaluation scores were good to outstanding for the content and usefulness
      of the course presentations, critiques by faculty, and discussion sessions.
      Interviews with participants indicated that a majority completed or were working
      on their projects within four years of completing the course. CONCLUSIONS: RU and
      some of its components (pursuing a literature search, making a practice change)
      are not processes that most nurses are familiar with, but these processes can be
      taught to nurses with focused clinical concerns. IMPLICATIONS FOR NURSING: An RU
      course with a low faculty-to-student ratio, adequate course materials, and
      systematic instruction can lead to research-based changes in practice.

PMID- 14722597
TI  - Anxiety and quality of life of women who receive radiation or chemotherapy for
      breast cancer.
AB  - PURPOSE/OBJECTIVES: To examine quality of life (QOL) and anxiety in a sample of
      women receiving radiation or chemotherapy for breast cancer. DESIGN:
      Longitudinal, descriptive. SETTING: A cancer center in the southeastern United
      States. SAMPLE: 48 women participated; 17 received radiation and 31 received
      chemotherapy. METHODS: The Ferrans and Powers Quality of Life Index (QLI) and
      Speilberger's State-Trait Anxiety Inventory (STAI) were administered. The QLI was
      administered at the start of treatment and one year later. The STAI was
      administered at the start of treatment. The state portion of the STAI also was
      administered 4 weeks and 12 weeks after the start of treatment. MAIN RESEARCH
      VARIABLES: QOL and anxiety. FINDINGS: Total QOL improved significantly over time
      for the entire sample, as did scores on the health/functioning,
      psychological/spiritual, and family subscales of the QLI. No significant
      differences existed for total QOL or any subscales by treatment. Trait anxiety
      was significantly higher for women receiving chemotherapy, and state anxiety was
      significantly higher at all three measurement times for the women. State anxiety
      did not decrease significantly over the course of the treatment for either group.
      Trait anxiety and state anxiety at the start of treatment were significantly
      negatively correlated with total QLI score and the psychological/spiritual
      subscale. State anxiety at the start of treatment also was significantly
      negatively correlated with total QOL and the health/functioning and
      psychological/spiritual QLI subscales both at the start of treatment and one year
      later. CONCLUSIONS: QOL improves over time for women who have received radiation
      or chemotherapy. Women receiving chemotherapy have higher anxiety scores, and
      higher anxiety at the start of treatment is associated with decreased QOL at the
      start of treatment and postdiagnosis. IMPLICATIONS FOR NURSING: Nursing
      interventions to reduce anxiety at the start of treatment, especially for
      chemotherapy recipients, are indicated. Research also should target methods to
      reduce anxiety at the start of treatment.

PMID- 14722598
TI  - Using technology to develop and distribute patient education storyboards across a
      health system.
AB  - PURPOSE/OBJECTIVES: To describe the successful implementation of a centrally
      designed and managed patient education storyboard project using Microsoft
      PowerPoint in a large multihospital system and physician-based practice settings.
      DATA SOURCES: Journal articles, project evaluation, and clinical and educational
      experience. DATA SYNTHESIS: The use of posters, bulletin boards, and storyboards
      as educational strategies has been reported widely. Two multidisciplinary
      committees applied new technology to develop storyboards for patient, family, and
      general public education. CONCLUSIONS: Technology can be used to coordinate
      centralized development of patient education posters, improving accuracy and
      content of patient education across a healthcare system while streamlining the
      development and review process and avoiding duplication of work effort.
      IMPLICATIONS FOR NURSING: Storyboards are excellent sources of unit-based
      current, consistent patient education; reduce duplication of efforts; enhance
      nursing computer competencies; market nursing expertise; and promote nurse
      educators.

PMID- 14722599
TI  - Politics, religion, and nursing education.

PMID- 14722600
TI  - Chemotherapy-induced vomiting in women treated for breast cancer.
AB  - PURPOSE/OBJECTIVES: To describe the incidence and intensity of vomiting in women
      receiving chemotherapy treatment for breast cancer since the advent of 5-HT3
      antagonists. DESIGN: Longitudinal, descriptive. SETTING: 7 outpatient oncology
      clinics situated in hospitals, 5 outpatient oncology clinics associated with
      major teaching universities, 27 private outpatient oncology practices, and 1
      outpatient clinic located in a county hospital. SAMPLE: Typical participants (N =
      303) were 51.9 years, Caucasian (79%), married or partnered (65%), born U.S.
      citizens (93%), heterosexual (96%), living with someone (84%), and high school
      graduates (82%). METHODS: Baseline and poststudy questionnaires and a daily diary
      of vomiting through two cycles of chemotherapy (approximately two months) were
      used to collect data. MAIN RESEARCH VARIABLE: Vomiting experience. FINDINGS: The
      worst vomiting occurs three days after having chemotherapy for breast cancer. The
      types of oral antiemetics ordered for home use were changed between the two
      cycles of the study only 8% (n = 24) of the time. No demographic factors were
      associated with acute vomiting at times 1 or 2; younger age (r = -0.16; p =
      0.012) was associated with more vomiting. Delayed vomiting was associated with
      age and body mass index, and younger, heavier women experienced more vomiting.
      Minority women (n = 55) reported significantly more delayed vomiting than did
      Caucasian women (mean = 6.56 versus 2.82; t = 2.02; p less than 0.05).
      CONCLUSIONS: Vomiting continues to be a significant problem for some women
      receiving chemotherapy for breast cancer. IMPLICATIONS FOR NURSING: Oncology
      nurses can use the results from this study to provide anticipatory guidance for
      patients undergoing chemotherapy for breast cancer and to support efforts to
      provide appropriate symptom management for these women.

PMID- 14722601
TI  - Older women and breast cancer screening: research synthesis.
AB  - PURPOSE/OBJECTIVES: To identify the most beneficial ways to support older women
      as they make screening decisions using a systematic, epidemiologic, narrative
      review of research regarding benefits and burdens of breast cancer screening and
      treatment. DATA SOURCES: Medical and nursing research databases emphasizing women
      aged 60 and older. DATA SYNTHESIS: Older women can tolerate screening and
      treatment, yet they are underserved. The most frequently cited reason to explain
      this phenomenon is declining health status associated with aging. Research
      evidence does not support this claim. No evidence clearly describes relationships
      among health status, aging, and less screening or less aggressive treatment.
      CONCLUSIONS: Older women experience varied health problems. However, indications
      that they are less able than their younger counterparts to tolerate screening or
      treatment for breast cancer do not exist. IMPLICATIONS FOR NURSING: Further
      research in all aspects of breast cancer care in older women is required to
      define and describe risks and benefits of screening within a context of aging and
      changing health. Nurses should discuss the risks and benefits of screening with
      older women.

PMID- 14722602
TI  - The effect of education in managing side effects in women receiving chemotherapy
      for treatment of breast cancer.
AB  - PURPOSE/OBJECTIVES: To determine the effectiveness of informational audiotapes on
      self-care behaviors, state anxiety, and use of self-care behaviors; to describe
      the occurrence and intensity of common side effects in patients with breast
      cancer. DESIGN: Randomized clinical trial. SETTING: Outpatient chemotherapy
      clinics operated by a university center in a rural area. SAMPLE: 70 women
      receiving their first treatment of chemotherapy. METHODS: Subjects completed
      demographic data and the Spielberger State-Trait Anxiety instrument (stai). The
      experimental group received two audiotapes. At one and three months, subjects
      completed the modified nail self-care diary and stai via telephone. MAIN RESEARCH
      VARIABLES: State anxiety, side-effect severity, and use and efficacy of self-care
      behaviors. FINDINGS: The most frequent side effects were fatigue, nausea and
      vomiting, and taste change. The experimental group reported symptom improvements
      that were not found in the control group. The experimental group increased the
      use of recommended self-care behaviors, whereas the control group continued to
      use the same self-care behaviors without effectiveness. State anxiety for both
      groups diminished over time; however, anxiety in the control group was
      consistently higher. CONCLUSIONS: Audiotapes are effective teaching tools. Self
      care behaviors can be taught and can be effective in managing side effects.
      Anxiety was high in both groups, but the symptom decreased in the women who
      received audiotapes and telephone calls. IMPLICATIONS FOR NURSING: Constraints on
      nurses decrease the length of teaching time available, but audiotapes provide
      effective teaching and reinforcement of education. Anxiety in clinical
      environments interferes with patient learning. Teaching effective self-care
      behaviors enhances patients' independence, comfort, control, and quality of life.

PMID- 14722603
TI  - Reservoir: a dirty word in HIV.

PMID- 14722604
TI  - Disorders of lung matrix remodeling.
AB  - A set of lung diseases share the tendency for the development of progressive
      fibrosis ultimately leading to respiratory failure. This review examines the
      common pathogenetic features of these disorders in light of recent observations
      in both humans and animal models of disease, which reveal important pathways of
      lung matrix remodeling.

PMID- 14722605
TI  - Telomeres, stem cells, senescence, and cancer.
AB  - Mammalian aging occurs in part because of a decline in the restorative capacity
      of tissue stem cells. These self-renewing cells are rendered malignant by a small
      number of oncogenic mutations, and overlapping tumor suppressor mechanisms (e.g.,
      p16(INK4a)-Rb, ARF-p53, and the telomere) have evolved to ward against this
      possibility. These beneficial antitumor pathways, however, appear also to limit
      the stem cell life span, thereby contributing to aging.

PMID- 14722606
TI  - Cellular senescence in cancer treatment: friend or foe?
AB  - Damage to DNA, the prime target of anticancer therapy, triggers programmed
      cellular responses. In addition to apoptosis, therapy-mediated premature
      senescence has been identified as another drug-responsive program that impacts
      the outcome of cancer therapy. Here, we discuss whether induction of senescence
      is a beneficial or, rather, a detrimental consequence of the therapeutic
      intervention.

PMID- 14722608
TI  - The bone marrow leaves its scar: new concepts in pulmonary fibrosis.
AB  - Excess collagen deposition occurs in pulmonary fibrosis. A new study suggests
      that collagen overproduction may originate from cells derived from bone marrow
      precursors rather than parenchymal lung fibroblasts.

PMID- 14722607
TI  - Bmi1, stem cells, and senescence regulation.
AB  - Stem cells generate the differentiated cell types within many organs throughout
      the lifespan of an organism and are thus ultimately responsible for the longevity
      of multicellular organisms. Therefore, senescence of stem cells must be
      prevented. Bmi1 is required for the maintenance of adult stem cells in some
      tissues partly because it represses genes that induce cellular senescence and
      cell death.

PMID- 14722609
TI  - Bateman domains and adenosine derivatives form a binding contract.
AB  - Conserved pairs of CBS sequence motifs (named after cystathionine beta-synthase)
      found in a wide variety of proteins associate to form Bateman domains. A new
      study establishes that Bateman domains bind adenosyl compounds and regulate IMP
      dehydrogenase, CBS, chloride channels, and AMP-activated protein kinase. This
      discovery reveals how mutations in CBS sequences in these proteins cause
      hereditary diseases and provides a rich vista of conceptual opportunities for
      therapies in energy metabolism, obesity, diabetes, cancer, antivirals, and
      immunosuppression.

PMID- 14722610
TI  - Synapses and Sisyphus: life without paraplegin.
AB  - The family of neurodegenerative diseases known as hereditary spastic parapareses
      have diverse genetic loci, yet there is a remarkable convergence in the
      neuropathologic and neurologic phenotype. A report describing the construction of
      a transgenic mouse with a deletion of a nuclear-encoded mitochondrial protein
      involved in the regulation of oxidative phosphorylation suggests that this family
      of diseases may reflect activation of a final common pathway involving synaptic
      dysfunction that progresses to destruction of the presynaptic nerve terminal and
      axon.

PMID- 14722611
TI  - Soluble VEGF isoforms are essential for establishing epiphyseal vascularization
      and regulating chondrocyte development and survival.
AB  - VEGF is crucial for metaphyseal bone vascularization. In contrast, the angiogenic
      factors required for vascularization of epiphyseal cartilage are unknown,
      although this represents a developmentally and clinically important aspect of
      bone growth. The VEGF gene is alternatively transcribed into VEGF(120),
      VEGF(164), and VEGF(188) isoforms that differ in matrix association and receptor
      binding. Their role in bone development was studied in mice expressing single
      isoforms. Here we report that expression of only VEGF(164) or only VEGF(188) (in
      VEGF(188/188) mice) was sufficient for metaphyseal development. VEGF(188/188)
      mice, however, showed dwarfism, disrupted development of growth plates and
      secondary ossification centers, and knee joint dysplasia. This phenotype was at
      least partly due to impaired vascularization surrounding the epiphysis, resulting
      in ectopically increased hypoxia and massive chondrocyte apoptosis in the
      interior of the epiphyseal cartilage. In addition to the vascular defect, we
      provide in vitro evidence that the VEGF(188) isoform alone is also insufficient
      to regulate chondrocyte proliferation and survival responses to hypoxia.
      Consistent herewith, chondrocytes in or close to the hypoxic zone in
      VEGF(188/188) mice showed increased proliferation and decreased differentiation.
      These findings indicate that the insoluble VEGF(188) isoform is insufficient for
      establishing epiphyseal vascularization and regulating cartilage development
      during endochondral bone formation.

PMID- 14722612
TI  - Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses.
AB  - Mice containing a disruption of the Hexb gene have provided a useful model system
      for the study of the human lysosomal storage disorder known as Sandhoff disease
      (SD). Hexb(-/-) mice rapidly develop a progressive neurologic disease of
      ganglioside GM2 and GA2 storage. Our study revealed that the disease states in
      this model are associated with the appearance of antiganglioside autoantibodies.
      Both elevation of serum antiganglioside autoantibodies and IgG deposition to CNS
      neurons were found in the advanced stages of the disease in Hexb(-/-) mice; serum
      transfer from these mice showed IgG binding to neurons. To determine the role of
      these autoantibodies, the Fc receptor gamma gene (FcR gamma) was additionally
      disrupted in Hexb(-/-) mice, as it plays a key role in immune complex-mediated
      autoimmune diseases. Clinical symptoms were improved and life spans were extended
      in the Hexb(-/-)FcR gamma(-/-) mice; the number of apoptotic cells was also
      decreased. The level of ganglioside accumulation, however, did not change. IgG
      deposition was also confirmed in the brain of an autopsied SD patient. Taken
      together, these findings suggest that the production of autoantibodies plays an
      important role in the pathogenesis of neuropathy in SD and therefore provides a
      target for novel therapies.

PMID- 14722613
TI  - Mosaic analysis of insulin receptor function.
AB  - Insulin promotes both metabolism and growth. However, it is unclear whether
      insulin-dependent growth is merely a result of its metabolic actions. Targeted
      ablation of insulin receptor (Insr) has not clarified this issue, because of
      early postnatal lethality. To examine this question, we generated mice with
      variable cellular mosaicism for null Insr alleles. Insr ablation in approximately
      80% of cells caused extreme growth retardation, lipoatrophy, and hypoglycemia, a
      clinical constellation that resembles the human syndrome of leprechaunism. Insr
      ablation in 98% of cells, while resulting in similar growth retardation and
      lipoatrophy, caused diabetes without beta-cell hyperplasia. The growth
      retardation was associated with a greater than 60-fold increase in the expression
      of hepatic insulin-like growth factor binding protein-1. These findings indicate
      that insulin regulates growth independently of metabolism and that the number of
      insulin receptors is an important determinant of the specificity of insulin
      action.

PMID- 14722614
TI  - OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary
      glands.
AB  - Outer surface protein C (OspC) is a differentially expressed major surface
      lipoprotein of Borrelia burgdorferi. ospC is swiftly upregulated when spirochetes
      leave the Ixodes scapularis tick gut, migrate to the salivary gland, and exit the
      arthropod vector. Here we show that OspC strongly binds to the tick salivary
      gland, suggesting a role for OspC in spirochete adherence to this tissue. In vivo
      studies using a murine model of Lyme borreliosis showed that while OspC F(ab)(2)
      fragments did not influence either the viability of spirochetes or ospC gene
      expression, they did interfere with B. burgdorferi invasion of tick salivary
      glands. We then generated ospC knockout spirochetes in an infectious clone of B.
      burgdorferi and examined them within the vector. OspC-deficient or wild-type
      spirochetes persisted equally within the gut of unfed ticks and multiplied during
      the tick engorgement; however, unlike wild-type B. burgdorferi, the mutants were
      unable to invade salivary glands. Salivary gland colonization of OspC-deficient
      spirochetes was completely restored when this mutant was complemented in trans
      with a plasmid harboring the wild-type ospC gene. These studies conclusively
      demonstrate the importance of OspC in the invasion of tick salivary glands by B.
      burgdorferi, a critical step in the transmission of spirochetes from the
      arthropod vector to the mammalian host.

PMID- 14722615
TI  - Axonal degeneration in paraplegin-deficient mice is associated with abnormal
      mitochondria and impairment of axonal transport.
AB  - In several neurodegenerative diseases, axonal degeneration occurs before neuronal
      death and contributes significantly to patients' disability. Hereditary spastic
      paraplegia (HSP) is a genetically heterogeneous condition characterized by
      selective degeneration of axons of the corticospinal tracts and fasciculus
      gracilis. HSP may therefore be considered an exemplary disease to study the local
      programs mediating axonal degeneration. We have developed a mouse model for
      autosomal recessive HSP due to mutations in the SPG7 gene encoding the
      mitochondrial ATPase paraplegin. Paraplegin-deficient mice are affected by a
      distal axonopathy of spinal and peripheral axons, characterized by axonal
      swelling and degeneration. We found that mitochondrial morphological
      abnormalities occurred in synaptic terminals and in distal regions of axons long
      before the first signs of swelling and degeneration and correlated with onset of
      motor impairment during a rotarod test. Axonal swellings occur through massive
      accumulation of organelles and neurofilaments, suggesting impairment of
      anterograde axonal transport. Retrograde axonal transport is delayed in
      symptomatic mice. We speculate that local failure of mitochondrial function may
      affect axonal transport and cause axonal degeneration. Our data suggest that a
      timely therapeutic intervention may prevent the loss of axons.

PMID- 14722616
TI  - Bone marrow-derived progenitor cells in pulmonary fibrosis.
AB  - The origin of fibroblasts in pulmonary fibrosis is assumed to be intrapulmonary,
      but their extrapulmonary origin and especially derivation from bone marrow (BM)
      progenitor cells has not been ruled out. To examine this possibility directly,
      adult mice were durably engrafted with BM isolated from transgenic mice
      expressing enhanced GFP. Induction of pulmonary fibrosis in such chimera mice by
      endotracheal bleomycin (BLM) injection caused large numbers of GFP(+) cells to
      appear in active fibrotic lesions, while only a few GFP(+) cells could be
      identified in control lungs. Flow-cytometric analysis of lung cells confirmed the
      BLM-induced increase in GFP(+) cells in chimera mice and revealed a significant
      increase in GFP(+) cells that also express type I collagen. GFP(+) lung
      fibroblasts isolated from chimera mice expressed collagen and telomerase reverse
      transcriptase but not alpha-smooth muscle actin. Treatment of isolated GFP(+)
      fibroblasts with TGF-beta failed to induce myofibroblast differentiation.
      Cultured lung fibroblasts expressed the chemokine receptors CXCR4 and CCR7 and
      responded chemotactically to their cognate ligands, stromal cell-derived factor-1
      alpha and secondary lymphoid chemokine, respectively. Thus the collagen-producing
      lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor
      cells.

PMID- 14722617
TI  - Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in
      scleroderma fibroblasts.
AB  - The principal effect of TGF-beta1 on mesenchymal cells is its stimulation of ECM
      synthesis. Previous reports indicated the significance of the autocrine TGF-beta
      loop in the pathogenesis of scleroderma. In this study, we focused on Smad7 and
      Smurfs, principal molecules in the negative regulation of TGF-beta signaling, to
      further understand the autocrine TGF-beta loop in scleroderma. Scleroderma
      fibroblasts exhibited increased Smad7 levels compared with normal fibroblasts in
      vivo and in vitro. Smad7 constitutively formed a complex with the TGF-beta
      receptors, and the inhibitory effect of Smad7 on the promoter activity of human
      alpha2(I) collagen and 3TP-lux was completely impaired in scleroderma
      fibroblasts. Furthermore, the protein stability of TGF-beta receptor type I was
      significantly increased in scleroderma fibroblasts compared with normal
      fibroblasts. There was no significant difference in Smurf1 and Smurf2 levels
      between normal and scleroderma fibroblasts, and the transiently overexpressed
      Smurf1 and/or Smurf2 did not affect TGF-beta receptor type I protein levels in
      scleroderma fibroblasts. These results indicate that the impaired Smad7-Smurf
      mediated inhibitory effect on TGF-beta signaling might contribute to maintaining
      the autocrine TGF-beta loop in scleroderma fibroblasts. To our knowledge, this is
      the first report of a disturbed negative regulation of TGF-beta signaling in
      fibrotic disorders.

PMID- 14722618
TI  - Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice
      lacking Na/Ca exchanger 3.
AB  - We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein
      that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse
      mode) and thus controls intracellular Ca(2+) concentration. NCX3-deficient mice
      (Ncx3(-/-)) present a skeletal muscle fiber necrosis and a defective
      neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of
      the muscle fibers and at the neuromuscular junction. The defective neuromuscular
      transmission is characterized by the presence of electromyographic abnormalities,
      including low compound muscle action potential amplitude, a decremental response
      at low-frequency nerve stimulation, an incremental response, and a prominent
      postexercise facilitation at high-frequency nerve stimulation, as well as
      neuromuscular blocks. The analysis of quantal transmitter release in Ncx3(-/-)
      neuromuscular junctions revealed an important facilitation superimposed on the
      depression of synaptic responses and an elevated delayed release during high
      frequency nerve stimulation. It is suggested that Ca(2+) entering nerve terminals
      is cleared relatively slowly in the absence of NCX3, thereby enhancing residual
      Ca(2+) and evoked and delayed quantal transmitter release during repetitive nerve
      stimulation. Our findings indicate that NCX3 plays an important role in vivo in
      the control of Ca(2+) concentrations in the skeletal muscle fibers and at the
      neuromuscular junction.

PMID- 14722619
TI  - CBS domains form energy-sensing modules whose binding of adenosine ligands is
      disrupted by disease mutations.
AB  - CBS domains are defined as sequence motifs that occur in several different
      proteins in all kingdoms of life. Although thought to be regulatory, their exact
      functions have been unknown. However, their importance was underlined by findings
      that mutations in conserved residues within them cause a variety of human
      hereditary diseases, including (with the gene mutated in parentheses): Wolff
      Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase);
      retinitis pigmentosa (IMP dehydrogenase-1); congenital myotonia, idiopathic
      generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter
      syndrome (CLC chloride channel family members); and homocystinuria (cystathionine
      beta-synthase). AMP-activated protein kinase is a sensor of cellular energy
      status that is activated by AMP and inhibited by ATP, but the location of the
      regulatory nucleotide-binding sites (which are prime targets for drugs to treat
      obesity and diabetes) was not characterized. We now show that tandem pairs of CBS
      domains from AMP-activated protein kinase, IMP dehydrogenase-2, the chloride
      channel CLC2, and cystathionine beta-synthase bind AMP, ATP, or S-adenosyl
      methionine,while mutations that cause hereditary diseases impair this binding.
      This shows that tandem pairs of CBS domains act, in most cases, as sensors of
      cellular energy status and, as such, represent a newly identified class of
      binding domain for adenosine derivatives.

PMID- 14722620
TI  - Translational upregulation of folate receptors is mediated by homocysteine via
      RNA-heterogeneous nuclear ribonucleoprotein E1 interactions.
AB  - Cellular acquisition of folate is mediated by folate receptors (FRs) in many
      malignant and normal human cells. Although FRs are upregulated in folate
      deficiency and downregulated following folate repletion, the mechanistic basis
      for this relationship is unclear. Previously we demonstrated that interaction of
      an 18-base cis-element in the 5'-untranslated region of FR mRNA and a cystolic
      trans-factor (heterogeneous nuclear ribonucleoprotein E1 [hnRNP E1]) is critical
      for FR synthesis. However, the molecular mechanisms controlling this interaction,
      especially within the context of FR regulation and folate status, have remained
      obscure. Human cervical carcinoma cells exhibited progressively increasing
      upregulation of FRs after shifting of folate-replete cells to low-folate media,
      without a proportionate rise in FR mRNA or rise in hnRNP E1. Translational FR
      upregulation was accompanied by a progressive accumulation of the metabolite
      homocysteine within cultured cells, which stimulated interaction of the FR mRNA
      cis-element and hnRNP E1 as well as FR biosynthesis in a dose-dependent manner.
      Abrupt reversal of folate deficiency also led to a rapid parallel reduction in
      homocysteine and FR biosynthesis to levels observed in folate-replete cells.
      Collectively, these results suggest that homocysteine is the key modulator of
      translational upregulation of FRs and establishes the linkage between perturbed
      folate metabolism and coordinated upregulation of FRs.

PMID- 14722621
TI  - The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal
      axis activity under both stress and resting conditions.
AB  - The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts major
      physiological actions through three distinct receptor isoforms designated V1a,
      V1b, and V2. Among these three subtypes, the vasopressin V1b receptor is
      specifically expressed in pituitary corticotrophs and mediates the stimulatory
      effect of vasopressin on ACTH release. To investigate the functional roles of V1b
      receptor subtypes in vivo, gene targeting was used to create a mouse model
      lacking the V1b receptor gene (V1bR-/-). Under resting conditions, circulating
      concentrations of ACTH and corticosterone were lower in V1bR-/- mice compared
      with WT mice (V1bR+/+). The normal increase in circulating ACTH levels in
      response to exogenous administration of AVP was impaired in V1bR-/- mice, while
      corticotropin-releasing hormone-stimulated ACTH release in the V1bR-/- mice was
      not significantly different from that in the V1bR+/+ mice. AVP-induced ACTH
      release from primary cultured pituitary cells in V1bR-/- mice was also blunted.
      Furthermore, the increase in ACTH after a forced swim stress was significantly
      suppressed in V1bR-/- mice. Our results clearly demonstrate that the V1b receptor
      plays a crucial role in regulating hypothalamic-pituitary-adrenal axis activity.
      It does this by maintaining ACTH and corticosterone levels, not only under stress
      but also under basal conditions.

PMID- 14722623
TI  - Exploring the context of drug use: a problem-based learning course in
      pharmacoepidemiology for undergraduate science students.
AB  - The teaching of pharmacoepidemiology has been largely confined to health care
      professionals and graduate students. This paper reports an attempt to use problem
      based learning (PBL) to teach the elements of that discipline to undergraduate
      science students. Carefully sequenced problems led students to consider the
      following issues: the terms used in epidemiology, merits and demerits of
      different epidemiological study designs, pharmacovigilance, the nature of
      evidence in law and science, economic evaluation of drugs and the use of drugs in
      different cultures. The 12-week course was taken by students in their final term
      prior to graduation. Multiple evaluation procedures were used: specific forms for
      assessing tutorial participation, individual explorations assessed usually by
      written essays and problem-solving exercises. The course has received high
      ratings from the students. The observations over a 10-year period suggest that
      PBL is a feasible approach to teach the social dimensions of drug use.

PMID- 14722622
TI  - CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+
      T cells via a CD30-dependent mechanism.
AB  - CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent
      autoimmunity, and delay allograft rejection. It is not known, however, whether
      Treg cells suppress allograft rejection mediated by memory T cells, as the latter
      mount faster and stronger immune responses than their naive counterparts. Here we
      show that antigen-induced, but not naive, Treg cells suppress allograft rejection
      mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells
      induced by third-party antigens did not delay allograft rejection. In vivo and in
      vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells
      is significantly increased in the presence of antigen-induced Treg cells, while
      their proliferation remains unaffected. Importantly, neither suppression of
      allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed
      when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with
      anti-CD30 ligand Ab. This study therefore provides direct evidence that
      pathogenic memory T cells are amenable to suppression in an antigen-specific
      manner and identifies CD30 as a molecule that is critical for the regulation of
      memory T cell responses.

PMID- 14722624
TI  - Subcellular localization of aflatoxin biosynthetic enzymes Nor-1, Ver-1, and OmtA
      in time-dependent fractionated colonies of Aspergillus parasiticus.
AB  - The biosynthesis of aflatoxin in Aspergillus parasiticus is a complex process
      that involves the activities of at least 18 pathway enzymes. The distribution of
      these enzymes within fungal colonies and fungal cells is not clearly understood.
      The objective of this study was to investigate the distribution and subcellular
      location of Nor-1, Ver-1, and OmtA, which represent early, middle, and late
      enzymatic activities, respectively, in the aflatoxin biosynthetic pathway. The
      distribution of these three enzymes within A. parasiticus SU-1 was analyzed in
      time-fractionated, 72-h fungal colonies (fraction 1, 48-72 h; fraction 2, 24-48
      h; fraction 3, 0-24 h). Western blot analysis and immunofluorescence microscopy
      demonstrated the highest abundance of Nor-1, Ver-1, and OmtA in colony fraction
      2. Fungal tissues in this fraction were analyzed by immunoelectron microscopy.
      Nor-1 and Ver-1 were primarily localized to the cytoplasm, suggesting that they
      are cytosolic enzymes. OmtA was also detected in the cytoplasm. However, in cells
      located near the basal (substrate) surface of the colony, OmtA was predominantly
      detected in organelles tentatively identified as vacuoles. The role of this
      organelle in toxin biosynthesis is unclear. The relative distribution of OmtA to
      the cytoplasm or to vacuole-like organelles may depend on the age and/or
      physiological condition of the fungal cells.

PMID- 14722625
TI  - The osteoporotic pain experience.
AB  - Osteoporosis, a disease characterized by skeletal fragility, represents a major
      health problem, especially for postmenopausal women. This project is a pilot
      study exploring the female osteoporotic patient's understanding of her individual
      pain condition and investigating the potential of a structured nursing program,
      called the Osteoporotic Pain Program (OPP), to increase the patient's insight,
      skills and motivation to self help, and possibly reduce pain. Findings in other
      studies and the expertise of experienced clinical nurses formed the basis for the
      OPP, which consists of three elements: conversations between nurse and patient,
      pain curves, and body charts. Qualitative interviews, using a semi-structured
      guide, were conducted to explore the meaning of the program as seen from the
      perspective of the patients. Participating in the OPP proved meaningful to
      patients in two major ways, actively exploring one's pain and feeling empowered.
      The analysis lead to forming a main category, "Exploring the chronic pain
      situation", and five subcategories were identified: expressing one's pain,
      understanding one's pain, justifying one's pain, accepting medication, and
      entering a ready-to-act mode. Findings indicate that the OPP contributes to
      challenging the patients. Their self-efficacy increases, their actions change,
      and pain intensity appears to decrease.

PMID- 14722626
TI  - Long-term changes in bone metabolism, bone mineral density, quantitative
      ultrasound parameters, and fracture incidence after spinal cord injury: a cross
      sectional observational study in 100 paraplegic men.
AB  - To study the time course of demineralization and fracture incidence after spinal
      cord injury (SCI), 100 paraplegic men with complete motor loss were investigated
      in a cross-sectional study 3 months to 30 years after their traumatic SCI.
      Fracture history was assessed and verified using patients' files and X-rays. BMD
      of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part =
      UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial
      epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC),
      speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the
      proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and
      quantitative ultrasound (QUS) were plotted against time-since-injury and compared
      among four groups of paraplegics stratified according to time-since-injury (<1
      year, stratum I; 1-9 years, stratum II; 10-19 years, stratum III; 20-29 years,
      stratum IV). Biochemical markers of bone turnover (deoxypyridinoline/creatinine
      (D-pyr/Cr), osteocalcin, alkaline phosphatase) and the main parameters of calcium
      phosphate metabolism were measured. Fifteen out of 98 paraplegics had sustained a
      total of 39 fragility fractures within 1,010 years of observation. All recorded
      fractures were fractures of the lower limbs, mean time to first fracture being
      8.9 +/- 1.4 years. Fracture incidence increased with time-after-SCI, from 1% in
      the first 12 months to 4.6%/year in paraplegics since >20 years ( p<.01). The
      overall fracture incidence was 2.2%/year. Compared with nonfractured paraplegics,
      those with a fracture history had been injured for a longer time ( p<.01).
      Furthermore, they had lower Z-scores at FN, TEPI, and TDIA ( p<.01 to <.0001),
      the largest difference being observed at TDIA, compared with the nonfractured. At
      the lower limbs, BMD decreased with time at all sites ( r=.49 to.78, all
      p<.0001). At FN and TEPI, bone loss followed a log curve which leveled off
      between 1 to 3 years after injury. In contrast, Z-scores of TDIA continuously
      decreased even beyond 10 years after injury. LS BMD Z-score increased with time
      since-SCI ( p<.05). Similarly to DXA, QUS allowed differentiation of early and
      rapid trabecular bone loss (QUI.CALC) vs slow and continuous cortical bone loss
      (SOS.TIB). Biochemical markers reflected a disproportion between highly elevated
      bone resorption and almost normal bone formation early after injury. Turnover
      declined following a log curve with time-after-SCI, however, D-pyr/Cr remained
      elevated in 30% of paraplegics injured >10 years. In paraplegic men early
      (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and
      leads to an increasing fracture incidence with time-after-SCI.

PMID- 14722627
TI  - Comparison of the effects of calcium loading with calcium citrate or calcium
      carbonate on bone turnover in postmenopausal women.
AB  - Calcium supplementation is known to increase bone mineral density and decrease
      fractures, but the relative efficacy of different forms of calcium
      supplementation is not established. We compared the effects of calcium carbonate
      and calcium citrate on markers of bone resorption in older postmenopausal women
      in an open-labeled crossover study. Forty women were randomized to receive 1000
      mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a
      2-week washout without calcium supplements and 12 weeks treatment with the
      alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty
      four women (25 Caucasian, nine Hispanic) completed the study. No significant
      differences in the decrease in parathyroid hormone (PTH) or bone specific
      alkaline phosphatase or the increase in urinary calcium/creatinine were detected
      between the two treatments. However, calcium citrate supplementation decreased
      the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C
      telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%),
      compared to no significant change following calcium carbonate supplementation
      (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers
      of bone resorption significantly more than calcium carbonate in postmenopausal
      women, although no differences in their effects in calcium excretion or PTH were
      detected.

PMID- 14722628
TI  - Hand-held echocardiography with Doppler capability for the assessment of
      critically-ill patients: is it reliable?
AB  - OBJECTIVE: To evaluate the diagnostic capability of a hand-carried ultrasound
      device (HCU) in critically ill patients when using conventional transthoracic
      echocardiography (TTE) as a reference. DESIGN: Prospective, descriptive study.
      SETTING: Medical-surgical intensive care unit of a teaching hospital. PATIENTS:
      All patients requiring a TTE study were eligible. INTERVENTIONS: Each patient
      underwent an echocardiographic examination using a full-feature echocardiographic
      platform (Sonos 5500, Philips Medical Systems, Andover, MA) and a small battery
      operated device (SonoHeart Elite, SonoSite, Bothell, WA). The operators (level
      III training in echocardiography) were randomized (HCU vs. TTE) and they
      independently interpreted the echocardiograms at the patient bedside. RESULTS:
      During a 2-month period, 55 consecutive patients (age: 61+/-16 years, simplified
      acute physiology score 46+/-15, body mass index 26+/-7) were studied, 40 of them
      being mechanically ventilated (73%). The number of acoustic windows was
      comparable using HCU and TTE (2.3+/-0.8 vs. 2.4+/-0.8: P=0.24). The overall
      diagnostic accuracy of HCU was lower compared with conventional TTE (137/171 vs.
      158/171 clinical questions solved: P=0.002), reaching 80% and 92%, respectively.
      Despite its spectral Doppler capability, HCU missed diagnoses that were
      adequately identified by TTE: elevated left ventricular pressure ( n=2), relevant
      valvulopathy ( n=2) and moderate ( n=4) or severe ( n=2) pulmonary hypertension.
      Acute management was altered by HCU and TTE findings in 27 patients (49%) and 28
      patients (51%), respectively. CONCLUSIONS: In this study, HCU had a lower
      diagnostic accuracy compared with conventional TTE, despite its spectral Doppler
      capability. Further studies are needed to validate these evolving diagnostic
      tools in critical care settings.

PMID- 14722630
TI  - Acridine-orange test in neonates with nosocomial pneumonia.

PMID- 14722629
TI  - Inhaled nitric oxide therapy in neonates and children: reaching a European
      consensus.
AB  - Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has
      subsequently been used extensively in the management of neonates and children
      with cardiorespiratory failure. This paper assesses evidence for the use of iNO
      in this population as presented to a consensus meeting jointly organised by the
      European Society of Paediatric and Neonatal Intensive Care, the European Society
      of Paediatric Research and the European Society of Neonatology. Consensus
      Guidelines on the Use of iNO in Neonates and Children were produced following
      discussion of the evidence at the consensus meeting.

PMID- 14722631
TI  - Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe
      sepsis patients who died despite appropriate intensive care.
AB  - OBJECTIVE: To assess the levels of expression of the antiapoptotic gene Bcl-2 and
      the proapoptotic gene Bax in circulating mononuclear cells (CMNC) harvested
      during the course of severe sepsis (SS) in formerly non-immunocompromised
      patients undergoing hospital-acquired infection, in parallel to cytokine levels.
      DESIGN: Prospective study. SETTING: Intensive care unit. PARTICIPANTS: A total of
      24 patients without immunodeficiency undergoing standard goal-directed therapy
      for nosocomial SS, 10 critically ill patients without sepsis, and 10 healthy
      controls. INTERVENTIONS: Blood was collected before infection and within 12 h, 1,
      3 and 7 days after fever onset, to determine plasma concentrations of IL-6, IL
      10, TNF-alpha, C-reactive protein, whole blood cell counts, lymphocyte subsets,
      annexin V labelling for apoptosis, and Bax and Bcl-2 relative RNA expression by
      real-time polymerase chain reaction. RESULTS: SS patients displayed increased
      cytokine concentrations, TNF-alpha being significantly increased at full-blown
      sepsis. Within 12 h after onset of infection, lymphocyte counts were lower in SS
      patients than in critically ill controls ( p=0.001), and this phenomenon was
      marked in CD4+ and CD8+ subsets ( p<0.001). This was associated with enhanced
      apoptosis in CMNC (15.7+/-8.7% vs 3.4+/-2.1%, p<0.001) and a significant down
      expression of the Bcl-2 gene throughout the study ( p<0.05). In contrast, the
      expression of Bax did not change significantly. Within 12 h of fever onset, non
      survivors expressed a 10-fold down-expression of Bcl-2 when compared to survivors
      ( p<0.001). CONCLUSIONS: An early transient down-expression of the gene Bcl-2
      occurred in CMNC harvested from SS patients who died despite intensive care. In
      contrast, the expression of the gene Bax did not change significantly.

PMID- 14722632
TI  - Accuracy of pulse oximetry readings in an animal model of low perfusion caused by
      emerging pneumonia and sepsis.
AB  - OBJECTIVE: To test the effects of low perfusion caused by emerging sepsis on the
      performance of two new pulse oximetry techniques: Masimo SET in comparison with
      Nellcor Oxismart XL. DESIGN: Cohort study with random allocation of two pulse
      oximetry devices to two sensor sites. SETTING. University animal research
      facility. SUBJECTS: Twenty-five adult, anesthetized, ventilated rabbits.
      INTERVENTIONS: Pneumonia/sepsis was induced by tracheal instillation of E. coli.
      MEASUREMENTS AND RESULTS: Oxygen saturation was measured by pulse oximetry
      (SpO(2)) and recorded continuously until death. Arterial oxygen saturation
      (SaO(2)) was measured hourly by CO oximetry and whenever a difference of >5%
      between the devices occurred. SpO(2) sensors were positioned at both forelegs and
      switched hourly. There was no difference in total signal dropout time [median 3.8
      min (range 0.4-66.6 min) vs 3.3 min (range 0-94.5 min), Masimo SET vs Oxismart
      XL]. There were fewer episodes with a false SpO(2) reading [1 (range 0-7) vs 2
      (range 0-17)] using the Masimo SET vs the Oxismart XL as verified by CO oximetry;
      p<0.05. Average bias (SpO(2)-SaO(2)) was significantly different between the two
      devices, and variability of bias values increased across time with both devices.
      CONCLUSIONS: Both devices were capable to measure SpO(2) during most of the
      experimental time in this model of low perfusion and therefore appear to be
      highly sensitive to pick up a signal; however, low perfusion caused by emerging
      sepsis may result in inaccurate measurements with both devices. These episodes
      were less common with the Masimo SET vs the Oxismart XL.

PMID- 14722633
TI  - Effects of fluid challenge on gastric mucosal PCO2 in septic patients.
AB  - OBJECTIVE: To determine the effects of fluid challenge on systemic hemodynamic
      variables and gastric intramucosal partial pressure of carbon dioxide (PCO(2)) in
      septic patients. DESIGN: Short-term interventional study. SETTING: Medical
      surgical intensive care unit in a university hospital. PATIENTS: Twenty-four
      adult patients with severe sepsis or septic shock requiring volume replacement.
      All patients were studied within 24 h of onset of severe sepsis or septic shock.
      INTERVENTIONS: Five hundred milliliters of a 6% hydroxyethyl starch (HES)
      solution were administered in 30 min. MEASUREMENTS AND RESULTS: Complete
      hemodynamic data, blood samples, and gastric mucosal PCO(2) (automatic gas
      capnometry) determinations were obtained at baseline and 15 min after the end of
      fluid infusion. After fluid challenge, cardiac index (CI) increased from 3.8
      (range 2.9-4.2) to 4.2 (range 3.1-4.9) l/min m(-2) ( p<0.05). The PCO(2) gap
      decreased from 9.8 (range 6.9-26.0) to 8.5 (range 6.6-17.4) mm Hg ( p<0.05), but
      important individual variations were observed. We failed to observe significant
      relationships between changes in CI and in PCO(2) gap, or between indices of
      preload (pulmonary artery occluded pressure, right atrial pressure, and pulse
      pressure variations) and changes in PCO(2) gap. In addition, changes in PCO(2)
      gap and in (v-a) CO(2) were not related; however, changes in PCO(2) gap were
      related to baseline PCO(2) gap ( p=0.003), PEEP ( p=0.02), and cumulative doses
      of vasopressors ( p=0.02). CONCLUSIONS: The effects of fluid challenge on gastric
      mucosal PCO(2) are variable and related to baseline PCO(2) gap rather than to
      systemic variables. In general, rapid volume infusion decreases PCO(2) gap, but
      this effect is more pronounced in patients with presumably impaired mucosal
      perfusion.

PMID- 14722634
TI  - Irreversible apnoeic coma 35 years later. Towards a more rigorous definition of
      brain death?
AB  - The concept of brain death (BD) has been widely accepted by medical and lay
      communities in the Western world and is the basis of policies of organ retrieval
      for transplantation from brain-dead donors. Nevertheless, concerns still exist
      over various aspects of the clinical condition it refers to. They include the
      utilitarian origin of the concept, the substantial international variation in BD
      definitions and criteria, the equivalence between BD and the donor's biological
      death, the practice of retrieving organs from donors who are not brain-dead (as
      in non-heart-beating organ donor protocols), the proposal to abandon the dead
      donor rule and attempts to overcome these problems by adapting rules and
      definitions. Suggesting that BD, as it was originally proposed by the Harvard
      Committee, is more a moral than a scientific concept, we argue that current
      criteria do not empirically justify the definition of BD; yet they consistently
      identify a clinical condition in which organ retrieval can be morally and
      socially justified. We propose to revert to the old term of "irreversible coma"
      or, better yet, of "irreversible apnoeic coma", thus abandoning the presumption
      of diagnosing the death of all intracranial neurons and/or the patient's
      biological death. On the other hand, we think that a (re)definition of the vital
      status of donors identified on neurological criteria can only occur through a
      prior (re)definition of death, a task which is not only medical but societal.

PMID- 14722635
TI  - Effects of protective and conventional mechanical ventilation on pulmonary
      function and systemic cytokine release after cardiopulmonary bypass.
AB  - OBJECTIVE: To evaluate the effects of protective and conventional ventilation
      with or without positive end-expiratory pressure (PEEP), on systemic tumor
      necrosis factor-alpha, interleukin-6 levels and pulmonary function during open
      heart surgery. DESIGN: Prospective, randomized clinical study. SETTING: Single
      university hospital. PATIENTS AND PARTICIPANTS: Forty-four patients undergoing
      elective coronary artery bypass grafting surgery with cardiopulmonary bypass.
      INTERVENTIONS: Patients ventilated with (1) protective tidal volumes (6 ml/kg,
      respiratory rate: 15 breaths/min, PEEP 5 cmH(2)O, n=15) group PV; (2)
      conventional tidal volumes (10 ml/kg, respiratory rate: 9 breaths/min, PEEP 5
      cmH(2)O, n=14) group CV+PEEP and (3) conventional tidal volumes (10 ml/kg,
      respiratory rate: 9 breaths/min, n=15) without PEEP, group CV+ZEEP. Various
      pulmonary parameters, systemic TNF-alpha and IL-6 levels were determined
      throughout the study. MEASUREMENTS AND RESULTS: There were no differences among
      the groups regarding the systemic TNF- alpha and IL-6 levels. The plateau airway
      pressures of group PV were lower than those of groups CV+PEEP ( p=0.02) and
      CV+ZEEP ( p=0.001) after cardiopulmonary bypass. The shunt fraction of group PV
      was significantly lower than that of group CV+ZEEP 24 h after surgery ( p<0.05).
      Oxygenation and the alveolar-arterial oxygen difference were better in both PEEP
      groups than in group CV+ZEEP 24 h after the operation. CONCLUSIONS: We could not
      find any evidence that protective mechanical ventilation prevents some of the
      adverse effects of cardiopulmonary bypass on the lung, nor systemic cytokine
      levels, postoperative pulmonary function or length of hospitalization.

PMID- 14722636
TI  - Treatment of acute respiratory failure by helmet-delivered non-invasive pressure
      support ventilation in children with acute leukemia: a pilot study.
AB  - OBJECTIVE: To evaluate the feasibility of non-invasive ventilation (NIV) through
      a new interface-the helmet-in the treatment of acute respiratory failure (ARF) in
      hematologic children. DESIGN AND SETTING: Observational, non-randomized report of
      four consecutive cases. Pediatric Intensive Care Unit in a university hospital.
      PATIENTS AND METHODS: Four consecutive females (aged 9-17 years) affected by
      acute leukemia (3 acute lymphocytic leukemia [ALL], 1 acute myeloid leukemia
      [AML]) and with hypoxemic ARF (defined by severe dyspnea at rest, respiratory
      rate >30 breaths/min, PaO2:FiO2 <200 and active contraction of the accessory
      muscles). Pressure support ventilation was delivered via a helmet
      (CaStar,Starmed, Italy) by means of an ICU ventilator (Servo 300, Siemens Elema,
      Sweden). RESULTS: We evaluated the effect of pressure support ventilation
      delivered by helmet on blood gases, respiratory rate, hemodynamics, patient
      tolerance, complication rate and outcome. An improvement of oxygenation was
      uniformly observed within the first 3 h after admission. The helmet was well
      tolerated by all children. No complication was observed. Two patients were
      discharged from the PICU in stable clinical conditions, whereas the remaining two
      children overcame the respiratory distress but had non-respiratory complications
      and eventually died. CONCLUSION: Non-invasive ventilation via the helmet can
      offer effective ventilatory support and improve gas exchange in the treatment of
      ARF in pediatric hematologic patients. As already shown in adults, NIV may
      decrease the risk of life-threatening complications associated with invasive
      mechanical ventilation (MV), also in children with hematologic malignancies;
      moreover, it offers the possibility of an earlier approach to respiratory failure
      in this patient subset.

PMID- 14722637
TI  - Relation of cerebral tissue oxygenation index to central venous oxygen saturation
      in children.
AB  - OBJECTIVE: To evaluate the relationship between the cerebral tissue oxygenation
      index measured by near-infrared spectroscopy and central venous oxygen saturation
      (SvO2) after corrective surgery of congenital heart defects in children. DESIGN:
      Prospective observational clinical study. SETTING: A tertiary neonatal and
      paediatric intensive care unit for paediatric cardiology. PATIENTS: Neonates and
      children consecutively admitted to the paediatric cardiology intensive care unit
      after corrective surgery of non-cyanotic congenital heart defects. MEASUREMENTS
      AND RESULTS: Forty-three children were studied. Cerebral tissue oxygenation
      index, measured non-invasively by near-infrared spectroscopy, was compared to
      SvO2, measured by a catheter placed in the right atrium, and to haemodynamic and
      respiratory parameters. Pearson's correlation coefficients and p values were
      calculated. Simultaneously measured values for SvO2 (62.2+/-9.8%, 39.8-80.4%) and
      cerebral tissue oxygenation index (56.7+/-8.8%, 35.8-71.2%) showed a significant
      correlation ( r=0.52, p<0.001). CONCLUSION: Cerebral tissue oxygenation index and
      SvO2 are not interchangeable parameters, but cerebral tissue oxygenation index
      reflects the haemodynamic influence on cerebral oxygenation after cardiovascular
      surgery. Further work is necessary to confirm the clinical role of continuous non
      invasive measurement of cerebral tissue oxygenation index with regard to the
      variations of global systemic oxygen consumption after cardiac surgery in
      children.

PMID- 14722639
TI  - Evaluation of a triple-lumen central venous heparin-coated catheter versus a
      catheter coated with chlorhexidine and silver sulfadiazine in critically ill
      patients.
AB  - OBJECTIVE: To compare the incidence of catheter colonization and catheter-related
      bloodstream infections between heparin-coated catheters and those coated with a
      synergistic combination of chlorhexidine and silver sulfadiazine. DESIGN:
      Randomized, controlled clinical trial. SETTING: A 20-bed medical-surgical
      intensive care unit. PATIENTS: A total of 180 patients requiring the insertion of
      a trilumen central venous catheter. INTERVENTIONS. Patients were randomized to
      receive either a trilumen heparin or chlorhexidine and silver sulfadiazine-coated
      catheter. MEASUREMENTS: Catheter colonization was defined by a semiquantitative
      catheter tip culture yielding 15 or more colony-forming units or quantitative
      culture of 1,000 or more colony-forming units/ml. Catheter-related bloodstream
      infection as the isolation of the same microorganism from a peripheral blood
      culture and catheter tip. RESULTS: A total of 260 catheters were cultured. Out of
      132 heparin-coated catheters, 29 were colonized and out of 128 chlorhexidine and
      silver sulfadiazine-coated catheters, 13 were colonized ( p=0.03), relative risk
      RR=2.16 (1.18-3.97). This represents an incidence of 23.5 and 11.5 episodes of
      catheter colonization per 1,000 catheter-days, respectively ( p=0.0059), RR=2.04
      (1.05-3.84). Microorganisms isolated in catheter colonization from heparin-coated
      catheters were gram-positive cocci 23, gram-negative bacilli 7, and Candida spp
      4. In chlorhexidine and silver sulfadiazine-coated catheters were gram-positive
      cocci 6 and gram-negative bacilli 11 ( p=0.009). The incidence of catheter
      related bloodstream infections per 1,000 catheter-days was 3.24 in heparin-coated
      catheters and 2.6 in chlorhexidine and silver sulfadiazine-coated catheters (
      p=0.79), RR=1.22 (0.27-5.43). CONCLUSIONS: In critically ill patients the use of
      trilumen central venous catheters coated with chlorhexidine and silver
      sulfadiazine reduced the risk of catheter colonization due to prevention of gram
      positive cocci and Candida spp.

PMID- 14722640
TI  - Measurement of indocyanine green plasma disappearance rate by two different
      dosages.
AB  - OBJECTIVE: While using a transcutaneous system for assessment of liver function
      by indocyanine green plasma disappearance rate (ICG-PDR) in critically ill
      patients, we compared the agreement between ICG-PDR obtained by the recommended
      standard ICG dosage (0.5 mg/kg) and a reduced dosage (0.25 mg/kg). DESIGN:
      Clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS:
      Critically ill patients ( n=16, 5 female, 11 male) who underwent liver function
      monitoring by ICG-PDR for clinical indication. MEASUREMENTS AND RESULTS: We
      analyzed 31 pairs of ICG-PDR measurements by applying the recommended dosage (0.5
      mg/kg, ICG-PDR(0.5)) and a reduced dosage (0.25 mg/kg, ICG-PDR(0.25)). For each
      comparative measurement either first 0.5 mg/kg or 0.25 mg/kg of ICG was injected
      in a random fashion and followed by the corresponding dosage 60 min later. All
      patients were sedated and mechanically ventilated via a tracheal tube. Each
      patient was monitored by an ICG finger clip which was connected to a liver
      function monitoring system (LiMon, Pulsion Medical Systems, Germany). ICG
      PDR(0.25) was 2.7-25.0 %/min and ICG-PDR(0.5) 4.5-24.5 %/min, respectively.
      Linear regression analysis revealed ICG-PDR(0.25)=1.13.ICG-PDR(0.5)-0.66 %/min
      (r=0.95, p<0.0001) with a mean bias 1.0 %/min (standard deviation 2.5 %/min). The
      15 min residual rates were also highly correlated ( r=0.92, p<0.0001) with a mean
      bias of 0.3%. CONCLUSION: A reduced dosage of ICG (0.25 mg/kg) is sufficiently
      accurate for transcutaneous measurement of ICG-PDR in critically ill patients.

PMID- 14722641
TI  - Changes in FiO2 affect PaO2 with minor alterations in cerebral concentration of
      oxygenated hemoglobin during liquid ventilation in healthy piglets.
AB  - OBJECTIVE: To measure the impact of changes in the fraction of inspired oxygen
      (FiO2) on systemic and cerebral oxygen supply in gas and liquid ventilated
      healthy animals. DESIGN: Interventional prospective animal study. SETTING:
      University research laboratory. PARTICIPANTS: Ten healthy, new-born piglets.
      INTERVENTIONS: Variations in FiO2 during conventional mechanical ventilation
      (CMV) followed by partial liquid ventilation (PLV) with two different filling
      volumes of PF 5080 (10 vs. 30 ml/kg). MEASUREMENTS AND RESULTS: Arterial blood
      gases were obtained 15 min after changing FiO2 and concentrations of cerebral
      oxygenated and total hemoglobin were determined with near infrared spectroscopy.
      During CMV an increase in FiO2 1.0 was associated with a constant rise in PaO2
      but only a small increase in the cerebral concentration of oxygenated Hb.
      Initiation of PLV (at FiO2 of 1.0) caused a rapid drop in PaO2 towards values
      that were similar to CMV at FiO2 of 0.5. At FiO2 of 0.5 a reduction in oxygenated
      Hb was found in the 30 ml/kg filling group. Complete filling of the lungs with
      PFC caused a significant drop in total cerebral Hb concentration. CONCLUSIONS.
      According to our data, PLV in healthy lungs should be performed with a FiO2 of
      1.0 and a small filling volume to avoid deterioration in cerebral oxygen supply.

PMID- 14722642
TI  - Randomized trial of the effect of antipyresis by metamizol, propacetamol or
      external cooling on metabolism, hemodynamics and inflammatory response.
AB  - OBJECTIVE: We investigated the metabolic, hemodynamic, and inflammatory responses
      of pharmacological and physical therapies aimed at reducing body temperature in
      febrile critically ill patients. DESIGN AND SETTING: Open-label, randomized trial
      in a surgical ICU in a tertiary university hospital. PATIENTS: Thirty
      analgosedated, mechanically ventilated patients with a temperature of 38.5
      degrees C or higher were randomized to receive either intravenous metamizol,
      intravenous propacetamol, or external cooling. MEASUREMENTS AND RESULTS: Body
      temperature and metabolic and hemodynamic variables were recorded at baseline and
      during the following 4 h. Cytokine concentrations were assessed before and 4 and
      12 h after the initiation of antipyresis. Body temperature decreased
      significantly in all treatment groups. For a 1 degrees C temperature decrease,
      the energy expenditure index increased by 5% with external cooling and decreased
      by 7% and 8% in the metamizol and propacetamol groups, respectively. Metamizol
      induced a significant decrease in mean arterial pressure and urine output
      compared to baseline and to the other two groups. C-reactive protein increased
      over time, but compared to the other groups it was significantly lower in
      patients receiving metamizol after 4 h. Cytokine concentrations were not
      different among the three groups or over time, although interleukin 6 tended to
      decrease over time in the metamizol group. CONCLUSIONS: Metamizol, propacetamol,
      and external cooling equally reduced temperature. Considering the undesirable
      hemodynamic effects, metamizol should not be considered the first antipyretic
      choice in unstable patients. Propacetamol or external cooling should be
      preferred, although the latter should be avoided in patients unlikely to tolerate
      the increased metabolic demand induced by external cooling.

PMID- 14722643
TI  - Ultrasound diagnosis of alveolar consolidation in the critically ill.
AB  - OBJECTIVE: Alveolar consolidation is a basic concern in critically ill patients.
      Radiography is not a precise tool, and referral to CT raises problems (transport,
      irradiation). The aim of this study was to assess the utility of ultrasound in
      the diagnosis of alveolar consolidation. DESIGN: Prospective clinical study.
      SETTING: The medical ICU of a university-affiliated teaching hospital. PATIENTS:
      A total of 65 cases of alveolar consolidation proven on CT were compared to 53 CT
      controls. MEASUREMENTS: Alveolar consolidation was defined as a tissue-like
      pattern visible at the chest wall, arising from the pleural line and devoid of
      centrifugal inspiratory dynamics. RESULTS: Feasibility was 99%. In 65 cases of
      alveolar consolidation, ultrasound was positive in 59 and negative in 6. In 52
      analyzable controls, ultrasound was negative in 51 and positive in 1. Sensitivity
      of ultrasound was 90% and specificity 98%. A concordance test showed a Kappa
      coefficient of 0.89. Among 62 posterior locations on CT, ultrasound showed
      posterior consolidation patterns in 56 cases and was negative in 6. Ultrasound
      showed anterior involvement in all 3 cases of whole lung consolidation.
      CONCLUSIONS: Ultrasound provides a reliable non-invasive, bedside method for
      accurate detection and location of alveolar consolidation in critically ill
      patients.

PMID- 14722644
TI  - Permissive hypercapnia--role in protective lung ventilatory strategies.
AB  - "Permissive hypercapnia" is an inherent element of accepted protective lung
      ventilation. However, there are no clinical data evaluating the efficacy of
      hypercapnia per se, independent of ventilator strategy. In the absence of such
      data, it is necessary to determine whether the potential exists for an active
      role for hypercapnia, distinct from the demonstrated benefits of reduced lung
      stretch. In this review, we consider four key issues. First, we consider the
      evidence that protective lung ventilatory strategies improve survival and we
      explore current paradigms regarding the mechanisms underlying these effects.
      Second, we examine whether hypercapnic acidosis may have effects that are
      additive to the effects of protective ventilation. Third, we consider whether
      direct elevation of CO(2), in the absence of protective ventilation, is
      beneficial or deleterious. Fourth, we address the current evidence regarding the
      buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the
      potential exists for hypercapnia to exert beneficial effects in the clinical
      context. Direct administration of CO(2) is protective in multiple models of acute
      lung and systemic injury. Nevertheless, several specific concerns remain
      regarding the safety of hypercapnia. At present, protective ventilatory
      strategies that involve hypercapnia are clinically acceptable, provided the
      clinician is primarily targeting reduced tidal stretch. There are insufficient
      clinical data to suggest that hypercapnia per se should be independently induced,
      nor do outcome data exist to support the practice of buffering hypercapnic
      acidosis. Rapidly advancing basic scientific investigations should better
      delineate the advantages, disadvantages, and optimal use of hypercapnia in ARDS.

PMID- 14722645
TI  - Effects on skeletal muscle of intravenous glutamine supplementation to ICU
      patients.
AB  - OBJECTIVE: To evaluate the effect of four doses of intravenous glutamine
      supplementation on skeletal muscle metabolism. DESIGN: A prospective, blinded,
      randomized study. SETTING: The general Intensive Care Unit (ICU) of a university
      hospital. PATIENTS: ICU patients with multiple organ failure (n=40), who were
      expected to stay in the unit for more than five days. INTERVENTION: Patients
      received 0, 0.28, 0.57 or 0.86 g of glutamine per kg bodyweight per day
      intravenously for five days as part of an isocaloric, isonitrogenous and
      isovolumetric diet. RESULTS: Plasma glutamine concentration responded to
      glutamine supplementation with normalization of plasma levels in a dose-dependent
      way, while free muscle glutamine concentration, as well as muscle protein
      synthesis and muscle protein content, did not change significantly. CONCLUSION:
      Intravenous glutamine supplementation to ICU patients for a period of five days
      resulted in normalization of plasma glutamine concentrations in a dose-dependent
      way whereas muscle glutamine concentrations were unaffected.

PMID- 14722646
TI  - Adiponectin counteracts cytokine- and fatty acid-induced apoptosis in the
      pancreatic beta-cell line INS-1.
AB  - AIMS/HYPOTHESIS: Pancreatic beta-cell apoptosis is a common feature of Type 1 and
      Type 2 diabetes and leptin exerts an anti-apoptotic function in these cells. The
      beta-cell line INS-1 was used to test the hypothesis that the adipocyte hormone
      adiponectin might mediate an anti-apoptotic effect comparable to leptin. METHODS:
      Apoptosis was induced by culturing cells with a cytokine combination (interleukin
      1beta/interferon-gamma) or palmitic acid in absence or presence of leptin or the
      globular domain of adiponectin (gAcrp30), respectively. RESULTS: INS-1 cells had
      a prominent sensitivity towards cytokine- and fatty acid-induced apoptosis,
      resulting in about three- and six-fold increases in caspase 3 activation and DNA
      fragmentation, respectively. gAcrp30 strongly (50-60%) inhibited palmitic acid
      induced apoptosis, with a weaker effect against cytokine-induced apoptosis (35%).
      The same result was observed for leptin with both adipokines being non-additive.
      Reduction of apoptosis by an inhibitor of IkappaB-kinase (IKK) indicated the
      involvement of the nuclear factor (NF)-kappaB pathway in both cytokine- and fatty
      acid-induced apoptosis, however, leptin and gAcrp30 were unable to block NF
      kappaB activation. Cytokine- and fatty-acid-induced suppression of
      glucose/forskolin-stimulated insulin secretion was completely prevented through
      the action of gAcrp30, whereas leptin was only effective against lipotoxicity
      mediated beta-cell dysfunction. CONCLUSION/INTERPRETATION: Our data show that
      gAcrp30 partially rescues beta cells from cytokine- and fatty-acid-induced
      apoptosis and completely restores autoimmune- and lipotoxicity-induced
      dysfunction of insulin-producing cells. We suggest that gAcrp30 exerts its anti
      apoptotic function without modulating NF-kappaB activation. This novel beta cell
      protective function of gAcrp30 might serve to counteract autoimmune- and
      lipotoxicity-induced beta-cell destruction.

PMID- 14722647
TI  - Evidence for a local angiotensin-generating system and dose-dependent inhibition
      of glucose-stimulated insulin release by angiotensin II in isolated pancreatic
      islets.
AB  - AIMS/HYPOTHESIS: A local angiotensin-generating system has been found in the
      exocrine pancreas. This study aimed, primarily, to investigate the existence of a
      local angiotensin-generating system in the pancreatic islets and, secondly, to
      elucidate its role in regulating insulin secretion. METHODS: Real-time RT-PCR and
      western blot were used to investigate if angiotensin-generating components are
      present in the mouse pancreatic islets, which are subject to regulation by islet
      transplantation. The localisation of AT1-receptors in islets was investigated by
      immunohistochemistry. Batch-type incubations of isolated islets were applied for
      studying the influence of angiotensin II on the glucose-stimulated insulin
      release, glucose oxidation and (pro)insulin, and total protein biosynthesis.
      RESULTS: Major components, namely angiotensinogen, ACE, AT1- and AT2-receptors,
      were expressed in endogenous islets. AT1-receptors were localised to pancreatic
      beta cells. Exposure of the isolated islets to angiotensin II induced a dose
      dependent inhibition of glucose-stimulated insulin release and inhibited
      (pro)insulin biosynthesis. This inhibitory action was fully preventable by
      pretreatment of the islets with losartan, an AT1-receptor antagonist. We also
      investigated if the expression of these components was changed after islet
      transplantation. Notably, a markedly increased expression of mRNA for the AT1
      receptor was observed in islets retrieved from 4-week-old syngeneic islet
      transplants, a finding that was confirmed at the protein level.
      CONCLUSION/INTERPRETATION: These data indicate the existence of an islet
      angiotensin-generating system of potential importance in the physiological
      regulation of glucose-induced insulin secretion, thus diabetes mellitus. The
      increased expression of the AT1-receptor in islet transplants could have
      relevance to islet-graft function.

PMID- 14722648
TI  - An expression profile of human pancreatic islet mRNAs by Serial Analysis of Gene
      Expression (SAGE).
AB  - AIMS/HYPOTHESIS: The Human Genome Project seeks to identify all genes with the
      ultimate goal of evaluation of relative expression levels in physiology and in
      disease states. The purpose of the current study was the identification of the
      most abundant transcripts in human pancreatic islets and their relative
      expression levels using Serial Analysis of Gene Expression. METHODS: By cutting
      cDNAs into small uniform fragments (tags) and concatemerizing them into larger
      clones, the identity and relative abundance of genes can be estimated for a cDNA
      library. Approximately 49,000 SAGE tags were obtained from three human libraries:
      (i) ficoll gradient-purified islets (ii) islets further individually isolated by
      hand-picking, and (iii) pancreatic exocrine tissue. RESULTS: The relative
      abundance of each of the genes identified was approximated by the frequency of
      the tags. Gene ontology functions showed that all three libraries contained
      transcripts mostly encoding secreted factors. Comparison of the two islet
      libraries showed various degrees of contamination from the surrounding exocrine
      tissue (11 vs 25%). After removal of exocrine transcripts, the relative abundance
      of 2180 islet transcripts was determined. In addition to the most common genes
      (e.g. insulin, transthyretin, glucagon), a number of other abundant genes with
      ill-defined functions such as proSAAS or secretagogin, were also observed.
      CONCLUSION/INTERPRETATION: This information could serve as a resource for gene
      discovery, for comparison of transcript abundance between tissues, and for
      monitoring gene expression in the study of beta-cell dysfunction of diabetes.
      Since the chromosomal location of the identified genes is known, this SAGE
      expression data can be used in setting priorities for candidate genes that map to
      linkage peaks in families affected with diabetes.

PMID- 14722651
TI  - Insulin sensitivity in juvenile and adult Large White pigs of low and high
      birthweight.
AB  - AIMS/HYPOTHESIS: We have previously demonstrated poor glucose tolerance in adult
      pigs of naturally occurring low birthweight. The aim of this study was to examine
      sensitivity to insulin in juvenile (3-month-old) and adult (12-month-old) pigs of
      low and high birthweight. METHODS: Low (<1.47 kg) and high (>1.53 kg) birthweight
      piglets from 15 litters were studied at 3 (n=47) and 12 (n=17) months of age. At
      each age the selected pigs were tranquilised and catheters were inserted into the
      dorsal aorta and caudal vena cava under general anaesthesia. After recovery,
      insulin sensitivity was measured as the glucose decrement (mmol.l(-1).min(-1))
      during the first 10 min after an intravenous insulin bolus (0.5 IU/kg). Data
      (means +/- SEM) were analysed by the Student's t test, ANOVA and linear
      regression. RESULTS: The body weight of low birthweight female, but not male,
      pigs remained smaller than that of high birthweight pigs at 3 and 12 months of
      age. At 3 months, thinness at birth and rapid catch-up growth in the first month
      of life were associated with increased insulin sensitivity in males. In females
      thinness at 3 months was associated with reduced sensitivity to insulin. At 12
      months, early postnatal catch-up growth was associated with insulin resistance,
      irrespective of sex, when all data were combined. CONCLUSIONS/INTERPRETATION: The
      glucose intolerance previously observed in young adult pigs of low birthweight is
      probably due to insulin resistance. Early catch-up growth in low birthweight pigs
      was the clearest predictor of adult insulin resistance.

PMID- 14722650
TI  - Islet amyloid: a complication of islet dysfunction or an aetiological factor in
      Type 2 diabetes?
AB  - The role of islet amyloidosis in the onset and progression of Type 2 diabetes
      remains obscure. Islet amyloid polypeptide is a 37 amino-acid, beta-cell peptide
      which is co-stored and co-released with insulin. Human islet amyloid polypeptide
      refolds to a beta-conformation and oligomerises to form insoluble fibrils;
      proline substitutions in rodent islet amyloid polypeptide prevent this molecular
      transition. Pro-islet amyloid polypeptide (67 amino acids in man) is processed in
      secretory granules. Refolding of islet amyloid polypeptide may be prevented by
      intragranular heterodimer formation with insulin (but not proinsulin). Diabetes
      associated abnormal proinsulin processing could contribute to de-stabilisation of
      granular islet amyloid polypeptide. Increased pro-islet amyloid polypeptide
      secretion as a consequence of islet dysfunction could promote fibrillogenesis;
      the propeptide forms fibrils and binds to basement membrane glycosamino-glycans.
      Islet amyloid polypeptide gene polymorphisms are not universally associated with
      Type 2 diabetes. Transgenic mice expressing human islet amyloid polypeptide gene
      have increased islet amyloid polypeptide concentrations but develop islet amyloid
      only against a background of obesity and/or high fat diet. In transgenic mice,
      obese monkeys and cats, initially small perivascular deposits progressively
      increase to occupy 80% islet mass; the severity of amyloidosis in animal models
      is related to the onset of hyperglycaemia, suggesting that islet amyloid and the
      associated destruction of islet cells cause diabetes. In human diabetes, islet
      amyloid can affect less than 1% or up to 80% of islets indicating that islet
      amyloidosis largely results from diabetes-related pathologies and is not an
      aetiological factor for hyperglycaemia. However, the associated progressive beta
      cell destruction leads to severe islet dysfunction and insulin requirement.

PMID- 14722652
TI  - SNP3 polymorphism in apo A-V gene is associated with small dense LDL particles in
      Type 2 diabetes.

PMID- 14722653
TI  - Sustained cardiomyocyte apoptosis and left ventricular remodelling after
      myocardial infarction in experimental diabetes.
AB  - AIMS/HYPOTHESIS: Diabetes is known to reduce survival after myocardial
      infarction. Our aim was to examine whether diabetes is associated with enhanced
      cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling
      process in myocardium in rat. METHODS: Four weeks after intravenous
      streptozotocin (diabetic groups) or citrate buffer (controls) injection,
      myocardial infarction was produced by ligation of left descending coronary
      artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3
      methods. Collagen volume fraction and connective tissue growth factor were
      determined under microscope. Left ventricular dimensions were evaluated by
      echocardiography and planimetry. RESULTS: The number of apoptotic cardiomyocytes
      was equally high in diabetic and non-diabetic rats after 1 week from infarction.
      At 12 weeks after infarction the number of apoptotic cells was higher in the
      diabetic as compared to non-diabetic rats both in the border zone of infarction
      and in non-infarcted area. Correspondingly, left ventricular end diastolic
      diameter, relative cardiac weight, connective tissue growth factor-expression and
      fibrosis were increased in diabetic compared with non-diabetic rats with
      myocardial infarction. CONCLUSION/INTERPRETATION: Sustained cardiomyocyte
      apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced
      profibrogenic connective tissue growth factor expression were detected after
      myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be
      an important mechanism contributing to progressive dilatation of the heart and
      poor prognosis after myocardial infarction in diabetes.

PMID- 14722655
TI  - [What is Machiavellian intelligence? Views on a little appreciated side of the
      psyche].
AB  - Ethological and evolutionary psychological research has produced evidence that
      intelligence is not a monolithic functional entity but includes a number of
      specialized mental abilities to cope with life which even stem from diverse
      evolutionary origins. One of these subforms of intelligence is called
      "Machiavellian intelligence," named after the 15/16th century Italian politician
      and author, Niccolo Machiavelli. It provides individuals or groups with a means
      of social manipulation in order to attain particular goals. Thus, it builds the
      psychological basis for the display of power in social groups. Machiavellian
      intelligence can be observed and evaluated in bands of primates as well as in
      humans, and there are even tools for measurement in the latter.

PMID- 14722654
TI  - Modulation of insulin action.
AB  - Insulin is a key hormone regulating the control of metabolism and the maintenance
      of normoglycaemia and normolipidaemia. Insulin acts by binding to its cell
      surface receptor, thus activating the receptor's intrinsic tyrosine kinase
      activity, resulting in receptor autophosphorylation and phosphorylation of
      several substrates. Tyrosine phosphorylated residues on the receptor itself and
      on subsequently bound receptor substrates provide docking sites for downstream
      signalling molecules, including adapters, protein serine/threonine kinases,
      phosphoinositide kinases and exchange factors. Collectively, those molecules
      orchestrate the numerous insulin-mediated physiological responses. A clear
      picture is emerging of the way in which insulin elicits several intracellular
      signalling pathways to mediate its physiologic functions. A further challenge,
      being pursued by several laboratories, is to understand the molecular mechanisms
      that underlie insulin action at the peripheral level, deregulation of which
      ultimately leads to hyperglycaemia and Type 2 diabetes. We review how circulating
      factors such as insulin itself, TNF-alpha, interleukins, fatty acids and
      glycation products influence insulin action through insulin signalling molecules
      themselves or through other pathways ultimately impinging on the insulin
      signalling pathway. Understanding how the mechanism by which molecular insulin
      action is modulated by these factors will potentially provide new targets for
      pharmacological agents, to enable the control of altered glucose and lipid
      metabolism and diabetes.

PMID- 14722656
TI  - [Mild cognitive disorder. Questions of definition, diagnosis, prognosis and
      therapy].
AB  - The syndrome of mild cognitive impairment (MCI) is heterogeneous in terms of
      aetiology, psychopathology, and prognosis. It is characterised by cognitive
      deterioration significantly exceeding the decline attributable to aging but not
      reaching the severity of dementia. The prevalence of MCI is estimated to be 17%
      in the population over 65 years old. At neuropathological examination, a large
      proportion of patients with mild cognitive impairment, particularly of the
      amnestic type, show typical features of Alzheimer's disease. The former
      progresses to dementia at an annual rate of 10% to 15%. In some cases, however,
      there is stable impairment or remission. The neurodegenerative process of
      Alzheimer's disease can be demonstrated in at least some patients using
      volumetric magnetic resonance imaging, 18-FDG positron emission tomography, or
      biochemical markers in the cerebrospinal fluid. It is not yet known whether
      patients with mild cognitive impairment or at least those with predementia
      Alzheimer's disease can benefit from currently available symptomatic treatments.
      Patients with early-stage Alzheimer's are an important target group for treatment
      interventions aiming at slowing the neurodegenerative process.

PMID- 14722658
TI  - [Kanner autism. Course of the disorder in the 2nd and 3rd decade in 18 patients
      with special reference to social adjustment. Results of a qualitative
      retrospective study].
AB  - The development of Kanner autism in 18 patients (mean age 28 years) in their
      second and third decade was explored and recorded with respect to factors
      affecting social competence in adulthood. To validate the diagnoses, we used the
      Childhood Autism Rating Scale (CARS). A version of the Vineland Adaptive Behavior
      Scales (VABS) was employed to assess social adaptation. On average, the
      individuals showed socially adaptive skills typical for healthy children at the
      age of 4 years and 3 months. Seventy-two percent of the autistic persons showed a
      characteristic pattern: they scored highest in daily living skills and lowest in
      social skills, especially in interpersonal relationships, where they performed at
      an average age equivalent of only 2 years and 7 months! Correlation analysis was
      conducted between developmental factors due to the disorder on the one hand and
      socially adaptive skills on the other. It showed, among other results, that
      positive developmental tendencies during adolescence are related to better social
      adaptation in adulthood ( r=0.57).

PMID- 14722657
TI  - [Effect of antipsychotics on glutaminergic neural transmission in the animal
      model].
AB  - Post-mortem investigations have confirmed that glutamatergic NMDA, AMPA, and
      kainate receptors are involved in the pathophysiology of schizophrenia. It is
      still unclear, however, whether the altered number of receptors is caused by the
      disease itself or the medication. Therefore, animal models were investigated for
      effects of antipsychotic medication after treatment periods of up to 6 months,
      the results of which are summarized here. Generally, NMDA receptor binding was
      found to be increased in striatum and nucleus accumbens after therapy with
      haloperidol, whereas clozapine only increased the number of receptors in nucleus
      accumbens. While haloperidol led to an increase in AMPA receptors in the
      posterior cingulate gyrus, striatum, insular cortex, and n. accumbens, clozapine
      was found to elevate ligand binding in the anterior cingulate gyrus and
      infralimbic cortex. Although kainate receptor binding was increased in
      hippocampus by both antipsychotics, clozapine was significantly more effective.
      In conclusion, data reveal different effects from the typical neuroleptic
      haloperidol and the atypical antipsychotic clozapine. The results suggest that
      post-mortem findings in patients with schizophrenia may at least partially be
      explained by drug effects and plasticity changes induced by long-term medication
      with antipsychotics.

PMID- 14722659
TI  - [Mental competence and neuropsychologic impairments in demented patients].
AB  - The study aim was to examine if neuropsychological tests and clinical dementia
      scales identify incompetent patients with dementia. Eighteen demented outpatients
      (ICD-10: F00-F03) underwent psychiatric examination, neuropsychological testing,
      and formal (MacArthur Competence Assessment Tool Treatment, Hopkins Competency
      Assessment Test) and clinical assessment of competence. Clinical dementia scales
      but not neuropsychological testing correlate with formal and clinical assessment
      of competence in patients with dementia. Our results do not support a
      neuropsychological model of competence assessment. However, in cases with poor
      results in clinical dementia scales, clinicians should assess the patients'
      competence in more detail. It remains open which is the best and ethically
      grounded methodology for competence assessment.

PMID- 14722660
TI  - [The initial dysphoric reaction (IDR) to the first dose of neuroleptics].
AB  - Initial dysphoric response (IDR) is characterized by a negative affective
      reaction within 48 h after a neuroleptic test dose. Currently, there are three
      scales for measuring the IDR (Neuroleptic Dysphoria Scale, Dysphoric Response
      Index, Drug Attitude Inventory). The debate continues about the definition,
      measurement, and underlying aetiology of IDR. Nevertheless, with a prevalence of
      30%, the response is a clinically relevant phenomenon. Empirical data give some
      evidence of an association between IDR and short-term outcome. No correlation of
      IDR with pretreatment variables has been found yet (e.g. age, gender, and
      psychopathology at baseline, especially depression and hostility). With respect
      to aetiology, a negative subjective reaction to concurrent extrapyramidal side
      effects and direct dysaffective effects of some neuroleptics have been discussed.
      Other studies found that IDR might not be a specifically antipsychotic effect.
      Our first results give some evidence that patients treated with atypical
      antipsychotics experience IDR less often and less severely than those treated
      with conventional antipsychotics described in the literature. Further research
      should include placebo-controlled studies and the evaluation of specific
      pretreatment variables. To assess the aetiology of IDR, further basic research is
      needed.

PMID- 14722661
TI  - [Subjective experience of a computer-assisted cognitive training by patients with
      schizophrenia].
AB  - Cognitive training is an important aim of treatment for patients with
      schizophrenia. However, computer-based cognitive training is still not widely
      used, and there are reservations concerning the use of computers in psychiatric
      treatment. In a multicentre study, 64 patients with schizophrenia were
      investigated before and after completing a 5-week course of computer-based
      cognitive training using the program Cogpack. In addition to self-rating of
      computer anxiety (CARS) and subjective well-being (SWN), patients underwent
      semistructured interviews evaluating attitudes towards the training. The training
      was rated as highly acceptable by patients and experienced as very effective.
      Patients' expectations of possible training effects were largely met. The
      training ranked high in patients' judgement compared with other treatments
      received. Besides improvement in cognitive function (primary effect), patients
      enjoyed the training and reported increased self-esteem and progress in using
      computers (secondary effects). Computer anxiety scores at onset of treatment did
      not exceed normal values. After completion of the training, these scores were
      significantly reduced and subjective well-being significantly increased.

PMID- 14722662
TI  - [Post-traumatic embitterment disorder (PTED). Differentiation of a specific form
      of adjustment disorders].
AB  - Adaptation disorders are a heterogeneous group of mental disorders. Although they
      play a major role in clinical practice, are difficult to treat, and often lead to
      chronicity and disability, diagnostic algorithms are vague and scientific
      research is rare. Clinical practice has shown a subtype of adaptation disorder
      that is characterized primarily by lasting embitterment after exceptional though
      normal life events which violate basic beliefs. This disorder can be called post
      traumatic embitterment disorder (PTED). A case vignette and results of a pilot
      study are reported. Critical life events were found to be job loss in 38%,
      conflicts at work in 24%, death of a loved one in 14%, familial strain in 14%,
      and other events in 10%. When reminded of the critical event, patients report
      feelings of embitterment (85.7%), sadness (81.0%), anger (76.2%), or helplessness
      (75.0%). When standardized assessments are made, they fulfill criteria of various
      comorbid disorders such as GAD (38.1%), depression (33.3%) and dysthymia (33.3%),
      agoraphobia (28.6%), or panic (19.0%). Of the patients, 81% said they avoid
      places which remind them of the critical events. Impairments were suffered in
      work (70%), leisure (65%), and familial relations (57.1%).

PMID- 14722663
TI  - [A contribution to the psychopathology of obsessive-compulsive disorder].
AB  - On the basis of recent developments in neuroscience, modern neuropsychology makes
      great contributions to the psychopathology of obsessive-compulsive disorder
      (OCD). Those studies pay little attention to the will because of their cognitive
      orientation. However, the will forms an essential aspect of OCD according to
      Jaspers and Schneider. Based on a clinical case we discuss OCD from the point of
      view of will psychology. As our case concerns a schizophrenic psychosis, we focus
      here on OCD appearing in schizophrenia. For this approach we refer to classic
      neuropsychology which deals intensively with problems of the will. Accordingly,
      patients suffering from brain injuries are confined to habitual activities which
      follow unintentionally from the present situation. This sort of present-related
      spontaneousness is expressed in the concept "becoming." On the other hand,
      patients suffering from OCD are alienated from habitual activities. Lastly we
      discuss the relation between schizophrenia and OCD.

PMID- 14722664
TI  - [A case of schizophrenia simplex?].
AB  - In routine clinical work, the psychopathology of some patients makes distinct
      diagnosis more difficult for the psychiatrist. In schizophrenia, especially those
      patients with dominant autism, eccentric behaviour, and abnormalities of affect
      with no evidence of positive symptoms pose special diagnostic problems. We report
      a case with formal thought disorder, autism, altered interactional behaviour, and
      disturbed emotional expression with no characteristic schizophrenic perception
      disorders, delusions, or other positive symptoms. With the help of this exemplary
      case, we discuss the diagnostic dilemma in careful use of diagnostic criteria in
      diagnosing schizophrenia in such cases.

PMID- 14722665
TI  - [Problem-based learning in medical education. Integrated "Nervous System and
      Behavior" course at the Munich Ludwig Maximilian University].
AB  - The new curriculum for medical licensure in Germany focuses on interdisciplinary
      and problem-based learning. In recent years, first experiences with this learning
      model were gathered in several German medical schools conducting courses
      supplementing the traditional curriculum. This article describes the course
      "Nervous system and behavior" at Ludwig Maximilian University in Munich. This
      course was established in cooperation with Harvard University in Boston, USA (The
      Munich-Harvard Alliance) together with three other clinical courses and has run
      every semester since the winter of 1999. As this course integrates neuroscience
      disciplines with special emphasis on neurology and psychiatry, it may serve as a
      role model for the implementation of these subjects in a new curriculum. This
      article introduces the reader to its structure and elements as well as feedback
      from students.

PMID- 14722666
TI  - [Richard von Krafft-Ebing (1840-1902. In memory of the 100th anniversary of his
      death].
AB  - Richard von Krafft-Ebing was a famous psychiatrist and sex researcher. However,
      little is known reliably about his life and work. The author was the first with
      the opportunity to review Krafft-Ebing's papers, which only recently had become
      accessible. Based on original documents, Krafft-Ebing's history is outlined.
      While Krafft-Ebing as general psychiatrist only followed the ongoing
      modernization and liberalization in his field, he was a pioneer of modern
      forensic psychiatry in his writings, opinions, and especially his viewpoint,
      emphasizing individual rights and responsibilities. In the field of sexual
      psychopathology, he basically summarized known case reports but did not lay down
      theoretical or therapeutic foundations for modern sexual science.

PMID- 14722667
TI  - [On the 150th birthday of Paul Julius Mobius (1853-1907)].
AB  - In memory of Paul Julius Mobius (1853-1907) on the occasion of his 150th birthday
      Among his profession Leipzig neurologist and psychiatrist Paul Julius Mobius made
      a name for himself by clinical studies on singular neurological topics. Several
      of these contributions have been acknowledged until today by giving his name to
      these symptoms or illnesses (cf. 'Mobius sign', 'Mobius syndrome', 'Mobius
      disease'). It was also him who divided nervous illnesses into endogenous and
      exogenous ones. Furthermore, Mobius made significant contributions towards the
      understanding of the causes for some mental illnesses, e.g. it was him who
      postulated a psychogenic development of hysteria. Through his pathographies as
      well as his work as a major reviewer and editor of 'Schmidt's Annals of Domestic
      and Foreign Entire Medicine' Mobius became known to a greater public. Even more
      well-known, if not infamous, Mobius's name is for his pamphlet on 'The
      Physiological Mental Weakness of Woman'. As a result of it's repeated
      republication he was accused to be hating women and his major contributions
      towards the progress of the neurosciences have been neglected.

PMID- 14722668
TI  - Cytotoxic properties of immunoconjugates containing melittin-like peptide 101
      against prostate cancer: in vitro and in vivo studies.
AB  - BACKGROUND: Monoclonal antibodies (MAbs) can target therapy to tumours while
      minimising normal tissue exposure. Efficacy of immunoconjugates containing
      peptide 101, designed around the first 22 amino acids of bee venom, melittin, to
      maintain the amphipathic helix, to enhance water solubility, and to increase
      hemolytic activity, was assessed in nude mice bearing subcutaneous human prostate
      cancer xenografts. METHODS: Mouse MAbs, J591 and BLCA-38, which recognise human
      prostate cancer cells, were cross-linked to peptide 101 using SPDP. Tumour
      bearing mice were used to compare biodistributions of radiolabeled
      immunoconjugates and MAb, or received multiple sequential injections of
      immunoconjugates. Therapeutic efficacy was assessed by delay in tumour growth and
      increased mouse survival. RESULTS: Radiolabeled immunoconjugates and antibodies
      showed similar xenograft tropism. Systemic or intratumoural injection of
      immunoconjugates inhibited tumour growth in mice relative to carrier alone,
      unconjugated antibody and nonspecific antibody-peptide conjugates and improved
      survival for treated mice. CONCLUSIONS: Immunoconjugates deliver beneficial
      effects; further peptide modifications may increase cytotoxicity.

PMID- 14722669
TI  - Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new
      prostate cancer directed antibody.
AB  - BACKGROUND: Monoclonal antibodies (MAbs) are used for targeting agents to tumours
      while minimizing normal tissue exposure. METHODS: A new anti-prostate cancer MAb,
      BLCA-38, was radioiodinated (I125) and assessed for its ability to target
      subcutaneous human prostate cancer (DU-145) xenografts after systemic
      intraperitoneal administration. For comparison, the profile of J591 MAb (now in
      clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles
      were obtained at various times, by assessing injected dose/gram (%ID/g) and
      xenograft to blood (X/B) ratios. Microautoradiography of xenografts was
      performed. After conjugation with a melittin peptide toxin, the profiles of BLCA
      38 and J591 were compared with that of an irrelevant antibody, DS-1. RESULTS:
      Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant
      antigen-positive tumors was comparable, and there was no unusual localization in
      nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the
      %ID/g xenograft was decreased and they accumulated in kidneys, bladder and
      stomach. In contrast, the conjugates of irrelevant antibody showed no tumour
      targeting. Microautoradiography showed more tumour accumulation of MAbs than
      F(ab')2s or Fabs. CONCLUSIONS: BLCA-38 can target prostate cancer in vivo almost
      as effectively as J591. Given that J591 is used clinically, BLCA-38, which
      targets a different antigen, has potential for radioimmunoscintigraphy and for
      therapeutic targeting of prostate cancer.

PMID- 14722670
TI  - Identification of tumour antigens by serological analysis of cDNA expression
      cloning.
AB  - The identification of antigens that distinguish normal cells from cancer cells is
      an important challenge in the field of tumour immunology and immunotherapy. The
      immunoscreening of cDNA expression libraries constructed from human tumour
      tissues with antibodies in sera from cancer patents (SEREX: serological
      identification of antigens by recombinant expression cloning) provides a powerful
      approach to identify immunogenic tumour antigens. To date, over 2,000 tumour
      antigens have been identified from a variety of malignancies using SEREX. These
      antigens can be classified into several categories, of which the cancer/testis
      (CT) antigens appear to be the most attractive candidates for vaccine
      development. The SEREX-defined tumour antigens facilitate the identification of
      epitopes (antigenic peptides) recognised by antigen-specific cytotoxic T
      lymphocytes (CTLs) and provide a basis for peptide vaccine and gene therapy in a
      wide variety of human cancers. Moreover, some of these antigens seem to play a
      functional role in the pathogenesis of cancer.

PMID- 14722671
TI  - The use of gene function to identify the rate-limiting steps controlling cell
      fate.
AB  - The size and complexity of the genomes of mammals in general, and humans in
      particular, is such that it will take many years to utilise this information to
      produce a genuine understanding of the control of cell behaviour. Since there are
      tens of thousands of genes to consider, the task of identifying those which play
      the most significant roles, biologically and medically, is both crucial and very
      demanding. Here we emphasise the importance of functional approaches to answering
      this question, i.e. the application of techniques which use the function of the
      gene itself in identifying the critical rate-limiting steps in biological
      processes. In this review, we use the functional analysis of one of the most
      important of these processes, the control of survival and apoptosis, to
      illustrate the power of a number of functional genomic strategies.

PMID- 14722672
TI  - Immunological inhibition of carcinogenesis.
AB  - The combination of new information provided by fundamental immunology, along with
      the refinement of genetic engineering techniques has given scientists the
      capacity to produce vaccines able to inhibit the growth of most if not every
      transplantable tumor. However, when faced with already established tumors,
      vaccines fail to afford any significant protection. Many studies are underway
      which seek to overcome this gloomy situation. However, another possibility is to
      follow the indications provided by a large quantity of experimental data and to
      evaluate the possibility of using immunotherapy to prevent the initial stages of
      tumor growth. Is it possible to prevent an autologous tumor by means of a
      vaccination performed before tumor onset? Could antitumor vaccines be a new form
      of preventive medicine in the wake of Jenner, Pasteur, and other pioneers? In
      this paper it is our intention to review the results obtained by our laboratory
      in the attempt to use natural and adaptive immunity in the control of
      carcinogenesis. Natural immunity boosted by IL-12 and IL-2 significantly hampers
      the progression of mammary lesions occurring in HER-2/neu transgenic mice
      genetically predestined to develop lethal mammary carcinomas. Specific immunity
      elicited by DNA vaccination provides a much stronger inhibition of the
      development of mammary lesions, and a significant number of transgenic mice are
      tumor free at 1 year of age. These experimental data suggest the possibility of
      using immunity as a means of controlling preneoplastic lesions and protecting
      healthy persons at risk of developing cancer.

PMID- 14722673
TI  - Finding an optimal method for imaging lymphatic vessels of the upper limb.
AB  - Lymphoscintigraphy involves interstitial injection of radiolabelled particulate
      materials or radioproteins. Although several variations in the technique have
      been described, their place in clinical practice remains controversial.
      Traditional diagnostic criteria are based primarily on lymph node appearances but
      in situations such as breast cancer, where lymph nodes may have been excised,
      these criteria are of limited use. In these circumstances, lymphatic vessel
      morphology takes on greater importance as a clinical endpoint, so a method that
      gives good definition of lymphatic vessels would be useful. In patients with
      breast cancer, for example, such a method, used before and after lymph node
      resection, may assist in predicting the development of breast cancer-related
      lymphoedema. The aim of this study was to optimise a method for the visualisation
      of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were
      compared, and technetium-99m nanocolloid, a particulate material, was compared
      with (99m)Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve
      normal volunteers were each studied on two occasions. In three subjects, id
      (99m)Tc-HIG was compared with sc (99m)Tc-HIG, in three id (99m)Tc-nanocolloid was
      compared with sc (99m)Tc-nanocolloid, in three id (99m)Tc-HIG was compared with
      id (99m)Tc-nanocolloid and in three sc (99m)Tc-HIG was compared with sc (99m)Tc
      nanocolloid. Endpoints were quality of lymphatic vessel definition, the time
      after injection at which vessels were most clearly visualised, the rate constant
      of depot disappearance ( k) and the systemic blood accumulation rate as measured
      by gamma camera imaging over the liver or cardiac blood pool. Excellent
      definition of lymphatic vessels was obtained following id injection of either
      radiopharmaceutical, an injection route that was clearly superior to sc.
      Differences between radiopharmaceuticals were less clear, although after id
      injection, (99m)Tc-HIG gave images that were marginally but significantly better
      than those given by (99m)Tc-nanocolloid. Image quality correlated inversely with
      time after injection at which the best image was obtained, consistent with the
      notion that good vessel definition was dependent on a "narrow" bolus width. k was
      approximately three times higher after id injection than after sc injection but
      it was not significantly different between radiopharmaceuticals for either
      injection route. Intradermal (99m)Tc-HIG gave a cardiac blood pool signal that,
      over the first 60 min, increased about five times faster than that with sc
      (99m)Tc-HIG, but no clear difference was observed in the rate of increase in
      hepatic activity between id (99m)Tc-nanocolloid and sc (99m)Tc-nanocolloid. We
      conclude that id injection provides rapid access of radiotracers to lymphatic
      vessels, which is ideal for imaging lymphatic vessel morphology. (99m)Tc-HIG is
      marginally superior to nanocolloid for this purpose and, in drainage basins from
      which lymph nodes have been excised, is not handicapped by a potentially inferior
      ability, compared with radiocolloid, to image lymph nodes.

PMID- 14722674
TI  - Influence of TSH on uptake of [18F]fluorodeoxyglucose in human thyroid cells in
      vitro.
AB  - Recent clinical evidence suggests that positron emission tomography with fluorine
      18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid
      carcinomatous tissue at high than at low TSH levels. The aim of this study was to
      determine the influence of TSH on FDG uptake in human thyroid cells in vitro.
      Monolayers of human thyroid tissue were cultured after mechanical disintegration
      and enzymatic digestion of samples from patients undergoing surgery for nodular
      goitre. The purity of thyroid cell preparations was ascertained by
      immunohistochemical staining for the epithelial antigen KL-1, and their viability
      by measuring the synthesis of thyroglobulin in vitro. The cells were incubated
      with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was
      quantified as percent of whole FDG activity per well (% ID) or as % ID in
      relation to total protein mass. This experimental protocol was subsequently
      varied to study the effect of incubation time, glucose dependency and TSH.
      Furthermore, radio-thin layer chromatography was used to identify intracellular
      FDG metabolites. FDG accumulated in the thyroid cells linearly with time,
      doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled
      glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the
      value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6
      phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in
      vitro in a time- and concentration-dependent manner: Cells cultured at a TSH
      concentration of 50 micro U/ ml doubled FDG uptake compared to TSH-free
      conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of
      that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid
      cells in a time- and concentration-dependent manner. This supports the clinical
      evidence that in well-differentiated thyroid carcinomas, most of which are still
      TSH-sensitive, FDG-PET is more accurate at high levels of TSH.

PMID- 14722675
TI  - Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and
      [18F]FMISO in an experimental mammary carcinoma.
AB  - The first aim of this study was to compare the hypoxia imaging ability of
      fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) with that of fluorine-18
      fluoromisonimidazole ([18F]FMISO) in murine tumours of different sizes under two
      different oxygenation conditions. Secondly, we wanted to assess the
      biodistribution of the markers in normal tissues under similar conditions. Female
      CDF1 mice with a C3H mammary carcinoma grown on their backs were used. Tumours
      were size matched and animals breathed either normal air (21% O(2)) or carbogen
      gas (95% O(2) + 5% CO(2)). The gassing procedure was begun 5 min before the
      intravenous injection of either [18F]FETNIM or [18F]FMISO and continued until the
      mice were sacrificed at 120 min. Blood, tumour, muscle, heart, lung, liver,
      kidney and fat were removed, counted for radioactivity and weighed. The tumour
      and muscle were frozen and cut with a cryomicrotome into sections. The spatial
      distribution of radioactivity from the tissue sections was determined with
      digital autoradiography. Estimation of the necrotic fraction was made on sections
      from formalin-fixed tumours. Digital autoradiography showed that the whole tumour
      to-muscle radioactivity uptake ratios were significantly higher in normal air
      breathing mice than in carbogen-treated mice for both [18F]FETNIM (4.9+/-2.6 vs
      1.8+/-0.5; P<0.01) and [18F]FMISO (4.4+/-1.0 vs 1.5+/-0.4; P<0.01). The carbogen
      treatment had only slight effects on the biodistribution of either marker in
      normal tissues. The necrotic fraction determined in tumours did not correlate
      with the tumour volume or with the tumour-to-muscle radioactivity uptake ratio.
      This study shows that the uptake of both [18F]FETNIM and [18F]FMISO correlates
      with the oxygenation status in tumours. In addition, our data show no significant
      difference in the intratumoral uptake between the two markers. However,
      significantly higher radioactivity uptake values were measured for [18F]FMISO
      than for [18F]FETNIM in normal tissues.

PMID- 14722676
TI  - Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an
      uptake-related ablation strategy.
AB  - In our hospital, a 24-h radioiodine-131 ((131)I) uptake-related ablation strategy
      is used in patients with differentiated thyroid cancer to destroy thyroid
      remnants after primary surgery. In this strategy, low doses of (131)I are used,
      but data in the literature on its efficacy are conflicting. Therefore, we
      performed the present study to evaluate the clinical outcome of this ablation
      strategy. In this study, patients ( n=235) were selected who underwent
      thyroidectomy for differentiated thyroid cancer, followed by an ablative dose of
      (131)I. Approximately 6 months after ablation, treatment efficacy was evaluated
      using radioiodine scintigraphy and thyroglobulin (Tg) measurements. Successful
      ablation was defined as the absence of radioiodine uptake in the neck region
      (criterion 1). Tg values were determined 3-12 months after ablation (criterion
      2). Based on criterion 1, unsuccessful ablation was found in 43.0% of cases. Pre
      treatment uptake values were statistically significantly lower ( P=0.003) in
      successfully ablated patients (mean 5.4%) than in unsuccessfully ablated patients
      (mean 8.2%). Based on criterion 2, unsuccessful ablation was found in 52.4% of
      patients. The uptake-related ablation strategy, using low doses of (131)I, shows
      a relatively high treatment failure rate. Based on these results it is suggested
      that a lower ablation failure rate could be achieved by applying higher (131)I
      doses in the ablation of thyroid remnants in differentiated thyroid carcinoma
      patients. In the case of lymph node metastases a further dose adjustment may be
      advisable.

PMID- 14722677
TI  - Cerebral blood flow SPET in transient global amnesia with automated ROI analysis
      by 3DSRT.
AB  - The aim of this study was to determine the areas involved in episodes of
      transient global amnesia (TGA) by calculation of cerebral blood flow (CBF) using
      3DSRT, fully automated ROI analysis software which we recently developed.
      Technetium-99m L, L-ethyl cysteinate dimer single-photon emission tomography
      ((99m)Tc-ECD SPET) was performed during and after TGA attacks on eight patients
      (four men and four women; mean study interval, 34 days). The SPET images were
      anatomically standardized using SPM99 followed by quantification of 318 constant
      ROIs, grouped into 12 segments (callosomarginal, precentral, central, parietal,
      angular, temporal, posterior cerebral, pericallosal, lenticular nucleus,
      thalamus, hippocampus and cerebellum), in each hemisphere to calculate segmental
      CBF (sCBF) as the area-weighted mean value for each of the respective 12 segments
      based on the regional CBF in each ROI. Correlation of the intra- and post
      episodic sCBF of each of the 12 segments of the eight patients was estimated by
      scatter-plot graphical analysis and Pearson's correlation test with Fisher's Z
      transformation. For the control, (99m)Tc-ECD SPET was performed on eight subjects
      (three men and five women) and repeated within 1 month; the correlation between
      the first and second sCBF values of each of the 12 segments was evaluated in the
      same way as for patients with TGA. Excellent reproducibility between the two sCBF
      values was found in all 12 segments of the control subjects. However, a
      significant correlation between intra- and post-episodic sCBF was not shown in
      the thalamus or angular segments of TGA patients. The present study was
      preliminary, but at least suggested that thalamus and angular regions are closely
      involved in the symptoms of TGA.

PMID- 14722678
TI  - FDG-PET delayed imaging for the detection of head and neck cancer recurrence
      after radio-chemotherapy: comparison with MRI/CT.
AB  - In advanced head and neck cancer, an organ-sparing approach comprising radiation
      therapy combined with intra-arterial chemotherapy has become an important
      technique. However, the high incidence of residual masses after therapy remains a
      problem. In this study, we prospectively evaluated the use of 2-[18F]fluoro-2
      deoxy-D-glucose positron emission tomography (FDG-PET) delayed imaging for the
      detection of recurrence of head and neck cancer after radio-chemotherapy, and
      compared the FDG-PET results with those of magnetic resonance imaging (MRI) or
      computed tomography (CT). Forty-three lesions from 36 patients with head and neck
      cancer suspected to represent recurrence after radio-chemotherapy (median
      interval from therapy, 4 months) were studied. PET was performed at 2 h after FDG
      injection, and evaluated. The results were compared to those of contrast studies
      with MRI or CT performed within 2 weeks of the PET study, and to histological
      diagnosis (in all patients suspected of having recurrence) or clinical diagnosis.
      The lesion-based sensitivity (visual interpretation) and negative predictive
      value of FDG-PET (88% and 91%, respectively) were higher than those of MRI/CT
      (75% and 67% respectively). The specificity, accuracy and positive predictive
      value of FDG-PET (78%, 81% and 70%, respectively) were significantly ( P<0.05)
      higher than those of MRI/CT (30%, 47% and 39% respectively). Three of six
      patients with false positive findings had post-therapy inflammation. Receiver
      operating characteristic (ROC) analysis showed that retrospective evaluation with
      the standardised uptake ratio yielded the best results (sensitivity 87.5%,
      specificity 81.5%), followed by visual interpretation and then the tumour/neck
      muscle ratio. An FDG-PET delayed imaging protocol yielded significantly better
      results for the detection of recurrence of head and neck cancer after radio
      chemotherapy than MRI/CT. Because of the high negative predictive value of FDG
      PET (91.3%), if PET is negative, further invasive procedures may be unnecessary.

PMID- 14722679
TI  - Validation of 4D-MSPECT and QGS for quantification of left ventricular volumes
      and ejection fraction from gated 99mTc-MIBI SPET: comparison with cardiac
      magnetic resonance imaging.
AB  - The main aim of this study was to validate the accuracy of 4D-MSPECT in the
      assessment of left ventricular (LV) end-diastolic/end-systolic volumes (EDV, ESV)
      and ejection fraction (LVEF) from gated technetium-99m methoxyisobutylisonitrile
      single-photon emission tomography ((99m)Tc-MIBI SPET), using cardiac magnetic
      resonance imaging (cMRI) as the reference method. By further comparing 4D-MSPECT
      and QGS with cMRI, the software-specific characteristics were analysed to
      elucidate clinical applicability. Fifty-four patients with suspected or proven
      coronary artery disease (CAD) were examined with gated (99m)Tc-MIBI SPET (8
      gates/cardiac cycle) about 60 min after tracer injection at rest. LV EDV, ESV and
      LVEF were calculated from gated (99m)Tc-MIBI SPET using 4D-MSPECT and QGS. On the
      same day, cMRI (20 gates/cardiac cycle) was performed, with LV EDV, ESV and LVEF
      calculated using Simpson's rule. Both algorithms worked with all data sets.
      Correlation between the results of gated (99m)Tc-MIBI SPET and cMRI was high for
      EDV [ R=0.89 (4D-MSPECT), R=0.92 (QGS)], ESV [ R=0.96 (4D-MSPECT), R=0.96 (QGS)]
      and LVEF [ R=0.89 (4D-MSPECT), R=0.90 (QGS)]. In contrast to ESV, EDV was
      significantly underestimated by 4D-MSPECT and QGS compared to cMRI [130+/-45 ml
      (4D-MSPECT), 122+/-41 ml (QGS), 139+/-36 ml (cMRI)]. For LVEF, 4D-MSPECT and cMRI
      revealed no significant differences, whereas QGS yielded significantly lower
      values than cMRI [57.5%+/-13.7% (4D-MSPECT), 52.2%+/-12.4% (QGS), 60.0%+/-15.8%
      (cMRI)]. In conclusion, agreement between gated (99m)Tc-MIBI SPET and cMRI is
      good across a wide range of clinically relevant LV volume and LVEF values
      assessed by 4D-MSPECT and QGS. However, algorithm-varying underestimation of LVEF
      should be accounted for in the clinical context and limits interchangeable use of
      software.

PMID- 14722680
TI  - Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using
      149Tb-rituximab.
AB  - This study demonstrates high-efficiency sterilisation of single cancer cells in a
      SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets
      CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio
      immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after
      an intravenous graft of 5.10(6) Daudi cells resulted in tumour-free survival for
      >120 days in 89% of treated animals. In contrast, all control mice (no treatment
      or treated with 5 or 300 micro g unlabelled rituximab) developed lymphoma
      disease. At the end of the study period, 28.4%+/-4% of the long-lived daughter
      activity remained in the body, of which 91.1% was located in bone tissue and 6.3%
      in the liver. A relatively high daughter radioactivity concentration was found in
      the spleen (12%+/-2%/g), suggesting that the killed cancer cells are mainly
      eliminated through the spleen. This promising preliminary in vivo study suggests
      that targeted alpha therapy with (149)Tb is worthy of consideration as a new
      generation radio-immunotherapeutic approach.

PMID- 14722681
TI  - Complementary alternative medicine and nuclear medicine.
AB  - Complementary alternative medicines (CAMs), including food supplements, are taken
      widely by patients, especially those with cancer. Others take CAMs hoping to
      improve fitness or prevent disease. Physicians (and patients) may not be aware of
      the potential side-effects and interactions of CAMs with conventional treatment.
      Likewise, their known physiological effects could interfere with
      radiopharmaceutical kinetics, producing abnormal treatment responses and
      diagnostic results. Nuclear medicine physicians are encouraged to question
      patients on their intake of CAMs when taking their history prior to radionuclide
      therapy or diagnosis. The potential effect of CAMs should be considered when
      unexpected therapeutic or diagnostic results are found.

PMID- 14722682
TI  - Comparison of thallium-201 SPET and CT/MRI in the detection of residual/recurrent
      squamous cell carcinoma of the oral cavity.
AB  - This study was designed to compare the effectiveness of thallium-201 single
      photon emission tomography (SPET) and conventional imaging, comprising computed
      tomography (CT) and magnetic resonance imaging (MRI), in the detection of
      residual/recurrent squamous cell carcinoma (SCC) of the oral cavity. Thirty-two
      patients with clinically suspected recurrent SCC of the oral cavity were
      recruited. All patients underwent (201)Tl SPET and CT or MRI within 2 weeks. The
      final diagnoses were based on the histology of the biopsy specimen. (201)Tl SPET
      and CT/MRI both accurately detected 17 of 18 residual/recurrent tumours. CT/MRI
      yielded eight false-positive studies, whereas (201)Tl SPET successfully excluded
      all tumours. The sensitivity, specificity, positive and negative predictive
      values and accuracy of (201)Tl SPET for the detection of recurrent oral SCC were
      94%, 100%, 100%, 93% and 97%, respectively. The sensitivity, specificity,
      positive and negative predictive values and accuracy of CT/MRI for the detection
      of recurrent oral SCC were 94%, 43%, 68%, 86% and 72%, respectively. Thallium-201
      SPET is more accurate than conventional imaging (CT or MRI) in differentiating
      residual/recurrent oral SCC from post-therapy changes.

PMID- 14722683
TI  - Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence
      camera in oncology.
AB  - The aim of this study was to evaluate the in vivo performance of a prototype dual
      crystal [lutetium oxyorthosilicate (LSO)/sodium iodide (NaI)] dual-head
      coincidence camera (DHC) for PET and SPET (LSO-PS), in comparison to BGO-PET with
      fluorine-18 fluorodeoxyglucose (FDG) in oncology. This follows earlier reports
      that LSO-PS has noise-equivalent counting (NEC) rates comparable to partial ring
      BGO-PET, i.e. clearly higher than standard NaI DHCs. Twenty-four randomly
      selected oncological patients referred for whole-body FDG-PET underwent BGO-PET
      followed by LSO-PS. Four nuclear medicine physicians were randomised to read a
      single scan modality, in terms of lesion intensity, location and likelihood of
      malignancy. BGO-PET was considered the gold standard. Forty-eight lesions were
      classified as positive with BGO-PET, of which LSO-PS identified 73% (95% CI 60
      86%). There was good observer agreement for both modalities in terms of
      intensity, location and interpretation. Lesions were missed by LSO-PS in 13
      patients in the chest ( n=6), neck ( n=3) and abdomen ( n=4). The diameter of
      these lesions was estimated to be 0.5-1 cm. Initial results justify further
      evaluation of LSO-PS in specific clinical situations, especially if a role as an
      instrument of triage for PET is foreseen.

PMID- 14722684
TI  - Is the future of nuclear medicine written in the genes?

PMID- 14722685
TI  - p-[123I]iodo-L-phenylalanine for detection of pancreatic cancer: basic
      investigations of the uptake characteristics in primary human pancreatic tumour
      cells and evaluation in in vivo models of human pancreatic adenocarcinoma.
AB  - Pancreatic cancer is associated with the worst 5-year survival rate of any human
      cancer. This high mortality is due, in part, to difficulties in establishing
      early and accurate diagnosis. Because most tumours share the ability to
      accumulate amino acids more effectively than normal tissues and any other
      pathology, assessment of amino acid transport in tumour cells using radiolabelled
      amino acids has become one of the most promising tools for tumour imaging. This
      study investigated the potential of p-[(123)I]iodo-L-phenylalanine (IPA) for
      detection of pancreatic cancer by single-photon emission tomography. IPA affinity
      for pancreatic tumour was investigated in human pancreatic adenocarcinoma PaCa44
      and PanC1 cells, followed by analysis of the underlying mechanisms of tracer
      accumulation in neoplastic cells. Thereafter, IPA was evaluated for targeting of
      pancreatic tumours using SCID mice engrafted with primary human pancreatic
      adenocarcinoma cells, as well as in acute inflammation models in immunocompetent
      mice and rats. IPA accumulated intensively in human pancreatic tumour cells.
      Radioactivity accumulation in tumour cells following a 30-min incubation at 37
      degrees C/pH 7.4 varied from 41% to 58% of the total loaded activity per 10(6)
      cells. The cellular uptake was temperature and pH dependent and predominantly
      mediated by specific carriers for neutral amino acids, namely the sodium
      independent and L-leucine-preferring (L-system) transporter and the alanine-,
      serine- and cysteine-preferring (ASC-system) transporter. Protein incorporation
      was less than 8%. Biodistribution studies showed rapid localization of the tracer
      to tumours, reaching 10%+/-2.5% to 15%+/-3% of the injected dose per gram
      (I.D./g) in heterotopic tumours compared with 17%+/-3.5% to 22%+/-4.3% I.D./g in
      the orthotopic tumours, at 60 and 240 min post injection of IPA, respectively. In
      contrast, IPA uptake in the gastrointestinal tract and areas of inflammation
      remained moderate and decreased with time. Excellent tumour detection was
      obtained by gamma camera imaging. The specific and high-level targeting of IPA to
      tumour and the negligible uptake in the gastrointestinal tract and areas of
      inflammation indicate that p-[(123)I]iodo-L-phenylalanine is a promising tracer
      for differential diagnosis of pancreatic cancer.

PMID- 14722686
TI  - Heterozygote advantage fails to explain the high degree of polymorphism of the
      MHC.
AB  - Major histocompatibility (MHC) molecules are encoded by extremely polymorphic
      genes and play a crucial role in vertebrate immunity. Natural selection favors
      MHC heterozygous hosts because individuals heterozygous at the MHC can present a
      larger diversity of peptides from infectious pathogens than homozygous
      individuals. Whether or not heterozygote advantage is sufficient to account for a
      high degree of polymorphism is controversial, however. Using mathematical models
      we studied the degree of MHC polymorphism arising when heterozygote advantage is
      the only selection pressure. We argue that existing models are misleading in that
      the fitness of heterozygotes is not related to the MHC alleles they harbor. To
      correct for this, we have developed novel models in which the genotypic fitness
      of a host directly reflects the fitness contributions of its MHC alleles. The
      mathematical analysis suggests that a high degree of polymorphism can only be
      accounted for if the different MHC alleles confer unrealistically similar
      fitnesses. This conclusion was confirmed by stochastic simulations, including
      mutation, genetic drift, and a finite population size. Heterozygote advantage on
      its own is insufficient to explain the high population diversity of the MHC.

PMID- 14722687
TI  - MHC polymorphism under host-pathogen coevolution.
AB  - The genes encoding major histocompatibility (MHC) molecules are among the most
      polymorphic genes known for vertebrates. Since MHC molecules play an important
      role in the induction of immune responses, the evolution of MHC polymorphism is
      often explained in terms of increased protection of hosts against pathogens. Two
      selective pressures that are thought to be involved are (1) selection favoring
      MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen
      coevolution. We have developed a computer simulation of coevolving hosts and
      pathogens to study the relative impact of these two mechanisms on the evolution
      of MHC polymorphism. We found that heterozygote advantage per se is insufficient
      to explain the high degree of polymorphism at the MHC, even in very large host
      populations. Host-pathogen coevolution, on the other hand, can easily account for
      realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving
      pathogens mainly evade presentation by the most common MHC alleles in the host
      population, they provide a selective pressure for a large variety of rare MHC
      alleles. Provided that the host population is sufficiently large, a large set of
      MHC alleles can persist over many host generations under host-pathogen
      coevolution, despite the fact that allele frequencies continuously change.

PMID- 14722688
TI  - Identification of a novel Japanese flounder (Paralichthys olivaceus) CC chemokine
      gene and an analysis of its function.
AB  - A cDNA of Japanese flounder (Paralichthys olivaceus) CC chemokine designated as
      Paol-SCYA104 was cloned and sequenced. The cDNA contains an opening reading frame
      of 315 nucleotides encoding 104 amino acid residues. The full gene was cloned and
      sequenced from a BAC library. It has a length of approximately 750 bp from the
      start codon to the stop codon and is composed of four exons and three introns.
      Four cysteine residues are conserved in the same positions as those of mammalian
      and fish CC chemokines. Paol-SCYA104 gene was expressed in several organs,
      including peripheral blood leukocytes (PBLs), head kidney, trunk kidney, and
      spleen. The recombinant Paol-SCYA104 was expressed in Escherichia coli and the
      expressed protein was partially purified. The recombinant Paol-SCYA104 was able
      to attract Japanese flounder PBLs in a microchemotaxis chamber. On the other
      hand, a negative control, the fraction of the control cells carrying an
      expression vector lacking the Paol-SCYA104 cDNA, did not show chemotactic
      activity. These results indicate that Paol-SCYA104 probably acts as a CC
      chemokine.

PMID- 14722689
TI  - Some aspects of the physiological role of ion channels in the nervous system.
AB  - Recent analyses of the genomes of several animal species, including man, have
      revealed that a large number of ion channels are present in the nervous system.
      Our understanding of the physiological role of these channels in the nervous
      system has followed the evolution of biophysical techniques during the last
      century. The observation and the quantification of the electrical events
      associated with the operation of the ionic channels has been, and still is, one
      of the best tools to analyse the various aspects of their contribution to nerve
      function. For this reason, we have chosen to use electrophysiological recordings
      to illustrate some of the main functions of these channels. The properties and
      the roles of Na+ and K+ channels in neuronal resting and action potentials are
      illustrated in the case of the giant axons of the squid and the cockroach. The
      nature and role of the calcium currents in the bursting behaviour of the neurons
      are illustrated for Aplysia giant neurons. The relationship between presynaptic
      calcium currents and synaptic transmission is shown for the squid giant synapse.
      The involvement of calcium channels in survival and neurite outgrowth of cultured
      neurons is exemplified using embryonic cockroach brain neurons. This same
      neuronal preparation is used to illustrate ion channel noise and single-channel
      events associated with the binding of agonists to nicotinic receptors. Some
      features of the synaptic activity in the central nervous system are shown, with
      examples from the cercal nerve giant-axon preparation of the cockroach. The
      interplay of different ion conductances involved in the oscillatory behaviour of
      the Xenopus spinal motoneurons is illustrated and discussed. The last part of
      this review deals with ionic homeostasis in the brain and the function of glial
      cells, with examples from Necturus and squids.

PMID- 14722690
TI  - Population dynamics of Gluconacetobacter diazotrophicus in sugarcane cultivars
      and its effect on plant growth.
AB  - Different experiments have estimated that the contribution of biological nitrogen
      fixation (BNF) is largely variable among sugarcane cultivars. Which bacteria are
      the most important in sugarcane-associated BNF is unknown. However,
      Gluconacetobacter diazotrophicus has been suggested as a strong candidate
      responsible for the BNF observed. In the present study, bacteria-free
      micropropagated plantlets of five sugarcane cultivars were inoculated with three
      G. diazotrophicus strains belonging to different genotypes. Bacterial
      colonization was monitored under different nitrogen fertilization levels and at
      different stages of plant growth. Analysis of the population dynamics of G.
      diazotrophicus strains in the different sugarcane varieties showed that the
      bacterial populations decreased drastically in relation to plant age, regardless
      of the nitrogen fertilization level, bacterial genotype or sugarcane cultivars.
      However, the persistence of the three strains was significantly longer in some
      cultivars (e.g., MEX 57-473) than in others (e.g., MY 55-14). In addition, some
      strains (e.g., PAl 5(T)) persisted for longer periods in higher numbers than
      other strains (e.g., PAl 3) inside plants of all the cultivars tested. Indeed,
      the study showed that the inoculation of G. diazotrophicus may be beneficial for
      sugarcane plant growth, but this response is dependent both on the G.
      diazotrophicus genotype and the sugarcane variety. The most positive response to
      inoculation was observed with the combination of strain PAl 5(T) and the variety
      MEX 57-473. Although the positive effect on sugarcane growth apparently occurred
      by mechanisms other than nitrogen fixation, the results show the importance of
      the sugarcane variety for the persistence of the plant-bacteria interaction, and
      it could explain the different rates of BNF estimated among sugarcane cultivars.

PMID- 14722692
TI  - Complications of ENT infections: pseudoaneurysm of the internal carotid artery.
AB  - Ear, nose and throat infections are common, especially in children and young
      adults. Since the advent of antibiotics, complications from tonsillitis and
      pharyngeal abscess are rare, but potentially lethal. Vascular complications can
      be imaged with Doppler ultrasound and CT scan. The treatment of infectious
      vascular complications represents a significant challenge. We describe the case
      of a young girl presenting with a pseudoaneurysm of the internal carotid and
      thrombosis of the internal jugular vein. Endovascular therapy was utilized to
      treat the patient.

PMID- 14722693
TI  - Cystoscopic and DMSA findings in relation to types of reflux demonstrated on
      percutaneous direct radionuclide cystography in children.
AB  - BACKGROUND: The new technique of percutaneous direct radionuclide cystography
      (PDRC) allows the accurate demonstration of vesicorenal reflux under
      physiological conditions during resting and micturition phases. Five types of
      reflux have been described, the clinical relevance of which is uncertain.
      OBJECTIVE: To determine whether a relationship exists between the type of reflux
      identified on PDRC and the appearance of the ureteric orifice at cystoscopy or
      the prevalence of renal abnormalities. MATERIALS AND METHODS: The reports of 281
      PDRC examinations were reviewed and 76 children with reflux formed the population
      of this study. Studies of these children were reviewed to classify the reflux as
      types 1-5, and patient records were searched for cystoscopy and DMSA scan
      reports. RESULTS: Regardless of the type of reflux, the ureteric orifices were
      found to be open at cystoscopy in 60-66% of refluxing units. DMSA scan
      abnormalities were present in 68% of units with reflux at rest, 61% of units with
      reflux on micturition and 86% of units with reflux on both resting and
      micturition phases. In comparison with contralateral units that did not reflux,
      the presence of reflux had a significant association with openness of the
      ureteric orifice ( p<0.00001) and DMSA abnormality ( p<0.005). CONCLUSIONS:
      Reflux of any type is strongly associated with an open ureteric orifice. Units
      that reflux during both resting and micturition phases had a higher incidence of
      DMSA abnormality than those refluxing during one phase only, but this was not
      statistically significant.

PMID- 14722694
TI  - MRI of optic disc edema in childhood idiopathic intracranial hypertension.

PMID- 14722695
TI  - Significance of appendiceal thickening in association with typhlitis in pediatric
      oncology patients.
AB  - BACKGROUND: The management of pediatric oncology patients with imaging evidence
      of appendiceal thickening is complex because they are generally poor surgical
      candidates and often have confounding clinical findings. OBJECTIVE: We sought to
      determine the significance of appendiceal thickening in pediatric oncology
      patients who also had typhlitis. Specifically, we evaluated the impact of this
      finding on the duration of typhlitis, its clinical management, and outcome.
      MATERIALS AND METHODS: From a previous review of the management of typhlitis in
      90 children with cancer at our institution, we identified 4 with imaging evidence
      of appendiceal thickening. We compared colonic wall measurements, duration of
      typhlitis symptoms, management, and outcome of patients with appendiceal
      thickening and typhlitis to patients with typhlitis alone. RESULTS: There was no
      significant difference in duration of typhlitis symptoms between patients with
      typhlitis only (15.6+/-1.2 days) and those with typhlitis and appendiceal
      thickening (14.5+/-5.8 days; P=0.9). Two patients with appendiceal thickening
      required surgical treatment for ischemic bowel, and two were treated medically.
      Only one patient in the typhlitis without appendiceal thickening group required
      surgical intervention. There were no deaths in children with appendiceal
      thickening; two patients died of complications of typhlitis alone. CONCLUSION:
      Our findings suggest that appendiceal thickening does not predict a prolonged
      course of typhlitis in pediatric oncology patients, but it may indicate an
      increased risk of serious complications from this disease process.

PMID- 14722697
TI  - In vitro and ex vivo gene delivery into proximal tubular cells by means of laser
      energy--a potential approach for curing cystinuria?
AB  - Cystinuria is the cause of 1-2% of stones observed in adults and about 10% of
      those occurring in children. Recurrent stone formation and multiple operations
      cause considerable morbidity. We investigated the transfection efficiency of
      naked plasmid DNA in porcine kidney cells by applying holmium laser (Ho:YAG)
      energy in vitro as well as ex vivo in a porcine kidney papilla model. In the in
      vitro experiments, naked plasmid DNA was added to LLC-PK1 cells suspended in a
      medium and Ho:YAG laser applied with varying pulses. The transfection efficiency
      was measured by the expression of EGFP reporter gene in the cells by FACScan
      analysis and fluorescence microscopy. Ex vivo, papilla from porcine kidney was
      excised and naked plasmid DNA was added to the tissue in the medium. The laser
      was then applied and the cryosectioned tissue observed under fluorescence
      microscope. The efficiency of transfection in vitro significantly improved with
      the increase in impulses (P<0.01). Transfection at 50 impulses averaged 0.7+/
      0.3%, at 200 impulses 28.3+/-7.7%, and at 500 impulses 36.1+/-3.1%. The cell
      mortality rate increased with higher pulse rate up to 70%. Ex vivo trials showed
      transfection in extended regions of the tissue and also in the peripheral layers
      of the papilla. Our study indicates that the transfection of benign kidney cells
      by Ho:YAG is a promising new gene transfer strategy. The ex vivo trials showed
      that peripheral renal tissue layers are susceptible to transfection by Ho:YAG
      applied from the papillary surface.

PMID- 14722699
TI  - The use of decoding to analyze the contribution to the information of the
      correlations between the firing of simultaneously recorded neurons.
AB  - A new decoding method is described that enables the information that is encoded
      by simultaneously recorded neurons to be measured. The algorithm measures the
      information that is contained not only in the number of spikes from each neuron,
      but also in the cross-correlations between the neuronal firing including stimulus
      dependent synchronization effects. The approach enables the effects of
      interactions between the 'signal' and 'noise' correlations to be identified and
      measured, as well as those from stimulus-dependent cross-correlations. The
      approach provides an estimate of the statistical significance of the stimulus
      dependent synchronization information, as well as enabling its magnitude to be
      compared with the magnitude of the spike-count related information, and also
      whether these two contributions are additive or redundant. The algorithm operates
      even with limited numbers of trials. The algorithm is validated by simulation. It
      was then used to analyze neuronal data from the primate inferior temporal visual
      cortex. The main conclusions from experiments with two to four simultaneously
      recorded neurons were that almost all of the information was available in the
      spike counts of the neurons; that this Rate information included on average very
      little redundancy arising from stimulus-independent correlation effects; and that
      stimulus-dependent cross-correlation effects (i.e. stimulus-dependent
      synchronization) contribute very little to the encoding of information in the
      inferior temporal visual cortex about which object or face has been presented.

PMID- 14722700
TI  - Vertical eye movement-related type II neurons with downward on-directions in the
      vestibular nucleus in alert cats.
AB  - The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been
      regarded as key elements of the velocity-to-position integrator for vertical eye
      movements. This paper reports a class of type II vestibular neurons that receives
      input from the INC and carries vertical eye movement signals that appear to
      represent an intermediate stage of the integration process. Extracellular
      recordings were made from neurons in and near the vestibular nuclei in alert
      cats. We encountered 39 neurons that exhibited an intense burst of spikes for
      downward saccades and a position-related tonic activity during intersaccadic
      intervals (d-type II neurons). They had a very high saccadic sensitivity (4.3+/
      2.7 spikes/deg, mean +/- SD) as well as a high position sensitivity (3.2+/-1.6
      (spikes/sec)/deg). Unlike the bursts of motoneurons, the bursts of these neurons
      declined gradually with an exponential-like time course and lasted well beyond
      the end of saccades. The mean time constant of the burst decay was 139+/-43 ms.
      The d-type II neurons were excited with disynaptic or trisynaptic latencies
      following stimulation of the contralateral vestibular nerve. The responses to
      vertical head rotations suggested inputs from the contralateral posterior canal.
      The d-type II neurons were excited with short latencies following stimulation of
      the ipsilateral INC, suggesting that they receive a direct excitatory input from
      vertical eye movement-related INC neurons with downward on-directions. The d-type
      II neurons were located in the rostral portion of the vestibular nuclei and the
      underlying reticular formation. These results suggest that d-type II neurons may
      be interposed between the burst-tonic neurons in the INC and pure tonic neurons
      in the vestibular nuclei and contribute to the oculomotor velocity-to-position
      integration.

PMID- 14722701
TI  - Interception of targets using brief directional cues.
AB  - There are time delays in visuomanual and oculomotor pathways, and some of these
      time delays may be due to the finite time required to process visual motion
      signals and to extract accurate information about the speed and direction of the
      motion. The present experiments were designed to ascertain the time required to
      obtain a reliable estimate of the direction of target motion. Subjects were asked
      to indicate the final direction of a moving target, which abruptly changed
      direction and shortly thereafter disappeared, by pointing to its expected
      emergence at the boundary of an occlusion. Subjects made small but consistent
      errors that overestimated the target's change in direction. These errors depended
      little on the amount of time the target was visible (ranging from 50 to 400 ms)
      after it changed direction. Pointing direction was strongly correlated with gaze,
      which was dominated by a saccade initiated shortly after the target changed
      direction. The pointing errors were explained by the fact that the saccade always
      intercepted the (occluded) target, but then continued in the same direction
      toward the boundary of the occlusion. The analysis reveals that target direction
      was estimated accurately even at the shortest viewing time.

PMID- 14722702
TI  - Memory for fingertip forces: passive hand muscle vibration interferes with
      predictive grip force scaling.
AB  - When subjects repetitively lift an object, the grip force they select is
      influenced by the mechanical object properties of the preceding lift. Similar
      effects on grip force scaling are observed whether the subsequent lift is
      performed with the same hand or the hand contralateral to the preceding lift.
      Here we demonstrate that passive vibration of the hand muscles involved in the
      generation of grip force in the interval between two blocks of lifting trials
      interferes with predictive grip force scaling. Following ten trials in which
      subjects lifted an object with constant mechanical properties with the dominant
      hand, muscle vibration was given to the first interosseus and adductor pollicis
      muscles of the dominant hand during a 10-min rest period. Compared with the last
      lift preceding vibration, peak rates of grip force increase and peak grip forces
      were scaled too high during the first lift following vibration whether the lift
      was made with the dominant or non-dominant hand. Subjects scaled grip force
      accurately to the object properties within three lifts following vibration. If
      subjects rested for 10 min after the first ten trials and received no vibration,
      then there was no significant difference in the peak grip force or its rate of
      increase between the last lift preceding rest and the first lift following it. We
      suggest that vibration impairs the memory processes responsible for predictive
      grip force scaling. Our data are consistent with the recent suggestion that these
      memory processes are neither specific for a certain motor action nor do they
      reflect internal representations of mechanical object properties.

PMID- 14722703
TI  - Sucrose consumption enhances the analgesic effects of cigarette smoking in male
      and female smokers.
AB  - RATIONALE: Nicotine has analgesic actions in experimental animals and humans.
      Moreover, the analgesic properties of nicotine in experimental animals are
      increased by intake of sweet-tasting nutritive fluids. It is important to
      determine if the effects of diet on nicotine-induced analgesia are limited to
      experimental animals, or if these effects can be translated from the laboratory
      to clinical research situations. OBJECTIVE: This study investigated whether
      intake of a sweet-tasting sucrose solution would enhance the pain relieving
      actions of nicotine, administered in the form of cigarette smoking, in male and
      female college-aged students. The effects of smoking and sucrose intake on mood
      were also examined. METHOD: Using the cold pressor test, pain thresholds and pain
      tolerance were determined in 24 male and 25 female smokers. Each participant was
      tested 4 times. On 2 of the test days, participants drank a sucrose-containing
      beverage, and on 2 of the days, drank water. Twenty-five minutes later,
      participants either smoked a cigarette or did not smoke. Participants were tested
      5 min later for their responses on the cold pressor test. To determine if mood
      was altered by smoking or sucrose intake, the Profile of Mood Scale was
      administered immediately preceding and following experimental manipulations.
      RESULTS: Cold threshold and cold tolerance were greater when participants were
      allowed to smoke than when they were not allowed to smoke. While men and women
      responded in a similar manner to the experimental manipulations, men displayed
      significantly greater cold threshold and cold tolerance than women. Sucrose
      consumption augmented the effects of smoking on cold threshold, but not on cold
      tolerance. Men reported feeling significantly more vigorous and less angry, and
      women reported feeling significantly less tense after they had smoked than when
      they had not smoked. Sucrose consumption did not alter self-reports of mood in
      either men or women. CONCLUSION: These findings suggest that sucrose augments the
      analgesic properties of nicotine in humans, as well as in experimental animals,
      and suggest that diet could serve as an adjunct in the control of pain.

PMID- 14722704
TI  - Self-reported psychopathological symptoms in recreational ecstasy (MDMA) users
      are mainly associated with regular cannabis use: further evidence from a combined
      cross-sectional/longitudinal investigation.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) has become a widely
      used recreational drug among young people. This is of great concern, since MDMA
      is neurotoxic in animal studies and its use has been associated with
      psychological distress and a variety of self-reported psychiatric symptoms.
      However, exploring the origins of psychopathology in ecstasy users is hampered by
      the frequent polydrug use and by the cross-sectional design of all
      investigations, so far. OBJECTIVES: The present study combines a cross-sectional
      with a longitudinal approach to further clarify the impact of the use of other
      illicit drugs on psychopathological symptoms reported by ecstasy users. METHODS:
      At baseline, we administered self-rating scales for impulsivity, sensation
      seeking and general psychological complaints to 60 recreational ecstasy users and
      30 matched controls. From the initial sample of ecstasy users, 38 subjects were
      re-examined 18 months later. RESULTS. At baseline, ecstasy users reported
      significantly more psychological complaints than controls. However, self-reported
      psychopathology was mainly associated with regular cannabis use. At follow-up,
      subjects who had abstained from ecstasy use during the follow-up period did not
      differ from those reporting continued consumption. In contrast, subjects with
      regular concomitant cannabis use during the follow-up period reported more
      anxiety, interpersonal sensitivity and obsessive-compulsive behaviour than
      cannabis-abstinent users. Finally, higher levels of obsessive-compulsive
      behaviour, interpersonal sensitivity, depression, anxiety, phobic anxiety and
      paranoid ideation were significantly correlated with the duration of regular
      interim cannabis use. CONCLUSIONS: The present findings suggest that self
      reported psychopathology in ecstasy users is predominantly attributable to
      concomitant use of cannabis. Abstinence from cannabis and not ecstasy seems to be
      a reliable predictor for remission of psychological complaints in ecstasy users.

PMID- 14722705
TI  - Naltrexone effects on alcohol consumption in a clinical laboratory paradigm:
      temporal effects of drinking.
AB  - BACKGROUND: This clinical laboratory study evaluated how the timing of drinking
      and subjective responses to alcohol are effected by the opioid antagonist
      naltrexone. METHODS: Forty non-treatment seeking alcoholics were randomly
      assigned to treatment with 50 mg naltrexone or matching placebo for 7 days. On
      day 7, they were administered an "initial drink" of alcohol (blood alcohol levels
      of between 20 and 30 mg%) in a bar-like setting. In a random fashion, half of the
      subjects in each group (naltrexone and placebo) had either immediate or delayed
      (40 min) access to up to 8 additional mini-drinks over a 2-h period. In the
      delayed group subjective reactions to alcohol were measured prior to access to
      more drinks. RESULTS: In the immediate access condition, subjects had similar
      drinking patterns, irrespective of whether they were taking naltrexone or
      placebo. However, in the delayed condition, naltrexone-treated subjects consumed
      fewer drinks and had a slower progression of drinking. There was a positive
      relationship between alcohol-induced stimulation and the number of drinks
      consumed in the placebo subjects but a negative correlation in the naltrexone
      subjects. CONCLUSIONS: These data suggest that the effectiveness of naltrexone on
      alcohol consumption may be somewhat dependent on pattern of consumption. Since
      naltrexone seems to disrupt the connection between alcohol-induced stimulation
      and further alcohol consumption, there may be a time-critical period between
      drinks necessary for alcoholics to benefit from its effects. These findings are
      consistent with clinical trial data that suggest a potential synergistic effect
      between relapse prevention therapies and opiate antagonist pharmacotherapy.

PMID- 14722706
TI  - Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed
      rats.
AB  - RATIONALE: New sleep disturbance model in rats is useful for estimating the
      characteristics of some hypnotics. OBJECTIVES: The present study was undertaken
      to investigate the utility of a sleep disturbance model by placing rats on a grid
      suspended over water using three kinds of hypnotics, that is, short-acting
      benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam)
      and long-acting barbiturate (phenobarbital). METHODS: Electrodes for measurement
      of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle
      of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign
      ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM
      and REM sleep were measured from 0900 to 1500 hours. RESULTS: In rats placed on
      the grid suspended over water up to 1 cm under the grid surface, not only
      triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep
      latency. Both flunitrazepam and phenobarbital were effective in increasing of
      total non-REM sleep time in rats placed on sawdust or the grid, and the effects
      of both drugs in rats placed on the grid were larger than those in rats placed on
      sawdust. Measurement of the hourly non-REM sleep time was useful for
      investigating the peak time and duration of effect of the three hypnotics.
      Phenobarbital showed a decrease in total REM sleep time in rats placed on the
      grid, although both triazolam and flunitrazepam were without effect. CONCLUSIONS:
      The present insomnia model can be used as a sleep disturbance model for testing
      not only the sleep-inducing effects but also the sleep-maintaining effects
      including non-REM sleep and REM sleep of hypnotics.

PMID- 14722707
TI  - Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA)
      users.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic upon
      central serotonin systems in experimental animals and probably also in humans.
      Serotonin is involved in the habituation, sensitization and prepulse inhibition
      (PPI) of the startle reflex. OBJECTIVES: To study the plasticity of startle
      reflex in currently abstinent MDMA users. METHODS: Electromyographic responses to
      acoustic startle stimuli (pulse alone and prepulse-pulse trials) were recorded in
      23 currently abstinent ecstasy users and 20 matched control subjects. Depending
      on the extent of their previous drug use ecstasy users were divided into two
      groups [life-time dose <90 (n=11) and > or =90 pills (n=12), respectively].
      RESULTS: There were no significant differences in habituation, sensitization or
      PPI of the startle reflex between the entire group of ecstasy users and controls.
      However, sensitization of the startle reflex was stronger in the > or =90
      compared with either the <90 MDMA pills or the control group. Correlations
      between patterns of drug use and startle parameters did not reach the level of
      significance, although users with a younger age at the onset of MDMA (and other
      drug) use tended to present with higher sensitization of the startle reflex.
      CONCLUSIONS: Heavy users of MDMA (and other recreational drugs) present with
      strong sensitization of the startle reflex. Nevertheless, it is unclear whether
      this finding is secondary to the use of MDMA and its well-recognized neurotoxic
      potential. Alternatively, strong sensitization might reflect a pre-existing trait
      predisposing to drug use. A clearer picture of the impact of ecstasy on startle
      plasticity may be obtained from longitudinal investigations.

PMID- 14722708
TI  - Case report: Successful riluzole augmentation therapy in treatment-resistant
      bipolar depression following the development of rash with lamotrigine.

PMID- 14722709
TI  - Multiplex PCR, amplicon size and hybridization efficiency on the NanoChip
      electronic microarray.
AB  - We tested the SNP typing protocol developed for the NanoChip electronic
      microarray by analyzing the four Y chromosome loci SRY1532, SRY8299, TAT, and
      92R7. Amplicons of different lengths containing the same locus were purified and
      addressed to the NanoChip array and fluorescently labelled reporter probes were
      hybridized to the amplicons. We demonstrated that as little as 10-30 fmol of 50
      bp DNA amplicons was sufficient to obtain strong and reproducible results. The
      hybridization to 50 bp amplicons was up to 10 times more efficient than the
      hybridization to 200 bp amplicons containing the same SNP. Hybridization to
      individual amplicons in multiplexes was less efficient suggesting that
      intramolecular and intermolecular interactions may block access to the target
      sequence on the NanoChip array. We observed a high risk of contamination with
      amplicons shorter than 60 bp and therefore, we recommend the use of 60-200 bp
      amplicons for SNP typing analysis on the NanoChip platform. In a comparative
      study, we typed the 5 Y chromosome loci M173, 92R7, P25, SRY1532, and M9 in 400
      males using the NanoChip SNP typing protocol and the SNaPshot kit. Concording
      results were obtained for all samples demonstrating the accuracy of the NanoChip
      SNP typing protocol.

PMID- 14722710
TI  - Development of a 13-locus PCR multiplex system for paternity testing.
AB  - In this study the development of a 13-locus multiplex-PCR system fitting the
      updated demands for paternity testing in Germany is described. For this purpose
      an existing multiplex PCR system that allows the simultaneous amplification of
      eight different STR loci together with the sex-specific locus amelogenin (
      genRESMPX-2, Serac, Germany) was extended. Whereas some of the primers were taken
      from the underlying multiplex system, suitable primer sequences were chosen for
      the STR loci D19S433, TPOX, TH01, D16S539, D5S818, D2S1338 and FGA. Primers of
      loci resulting in potentially overlapping fragment sizes were labelled with the
      fluorescent dyes 6-FAM, JOE and NED. Reaction conditions, such as annealing
      temperature, concentrations of primers and polymerase or buffer conditions were
      optimised to obtain a robust amplification and reproducible genotype analysis for
      various sample sources. Full DNA profiles from single source samples were
      reliably typed from template DNA amounts of as low as 120 pg, suggesting a
      potential use of this system also in forensic casework analysis. With a mean
      exclusion chance (MEC) of 99.9989% and a power of discrimination (P(D)) of about
      1x10(14) (Caucasians), the new multiplex PCR system provides a significant and
      sensitive system for forensic DNA analysis. On the basis of these studies, a
      commercial kit system is now provided by Serac (Bad Homburg, Germany, genRESMPX
      3).

PMID- 14722711
TI  - Topography of genetic loci in the nuclei of cells of colorectal carcinoma and
      adjacent tissue of colonic epithelium.
AB  - To determine the influence of increased gene expression and amplification in
      colorectal carcinoma on chromatin structure, the nuclear distances between pairs
      of bacterial artificial chromosome (BAC) clones with genomic separation from 800
      to 29,000 kb were measured and compared between the tumor and parallel epithelial
      cells of six patients. The nuclear distances were measured between the loci in
      chromosomal bands 7p22.3-7p21.3; 7q35-7q36.3; 11p15.5-11p15.4; 20p13; 20p12.2;
      20q11.21 and 20q12 where increased expression had been found in all types of
      colorectal carcinoma. The loci were visualized by three-dimensional fluorescence
      in situ hybridization using 22 BAC clones. Our results show that for short
      genomic separations, mean nuclear distance increases linearly with increased
      genomic separation. The results for some pairs of loci fell outside this linear
      slope, indicating the existence of different levels of chromatin folding. For the
      same genomic separations the nuclear distances were frequently shorter for tumor
      as compared with epithelial cells. Above the initial growing phase of the nuclear
      distances, a plateau phase was observed in both cell types where the increase in
      genomic separation was not accompanied by an increase in nuclear distance. The
      ratio of the mean nuclear distances between the corresponding loci in tumor and
      epithelium cells decreases with increasing amplification of loci. Our results
      further show that the large-scale chromatin folding might differ for specific
      regions of chromosomes and that it is basically preserved in tumor cells in spite
      of the amplification of many loci.

PMID- 14722713
TI  - Cornual heterotopic pregnancy: conservative treatment with transvaginal embryo
      reduction.
AB  - OBJECTIVE: The objective was to discuss a case of heterotopic cornual pregnancy
      managed with transvaginal embryo reduction. METHODS: A 22-year-old woman with
      heterotopic cornual pregnancy was treated with ultrasonographically guided
      transvaginal injection of potassium chloride into the thorax of ectopic fetus.
      RESULTS: Sixteen days after the procedure, the patient presented with pelvic pain
      and miscarriage ensued. Control examination 1 month and 3 months later revealed
      normal uterine cavity and partially resorbed ectopic material. CONCLUSION: This
      minimally invasive approach in a hemodynamically stable patient can be considered
      in the management of a first trimester heterotopic cornual pregnancy. However the
      patient must be informed for the risk of abortion related to the procedure.
      Nevertheless this approach can be a treatment option in cornual pregnancies
      without a simultaneous intrauterine gestation.

PMID- 14722714
TI  - Ovarian pregnancy with intrauterine device in situ.
AB  - INTRODUCTION: Since some reports have already suggested a higher rate of ovarian
      pregnancies in women using intrauterine device and some have not, an additional
      case report may be of interest for the literature purposes. CASE REPORT: In this
      case report we present an ovarian pregnancy in a patient with an intrauterine
      device in situ.

PMID- 14722715
TI  - Infection of human astrocytes and glioblastoma cells with Toxoplasma gondii:
      monocyte chemotactic protein-1 secretion and chemokine expression in vitro.
AB  - In immunocompromised hosts, disruption of toxoplasmic cysts and conversion from
      bradyzoites to tachyzoites occur in brain. In these areas, infiltrates of
      mononuclear cells are observed. In the murine toxoplasmosis model, recent data
      suggest that chemokines may play a role in leukocyte recruitment in the central
      nervous system (CNS). This study analyzed the monocyte chemotactic protein-1 (MCP
      1) secretion and chemokine expression after Toxoplasma gondii infection of human
      astrocytes, glioblastoma cells (U373) and fibroblasts (MRC5) in vitro. T. gondii
      infection of these CNS cells, astrocytes and glioblastoma cells significantly
      increased MCP-1 secretion, particularly for astrocytes. In our cellular models,
      the pattern of chemokine gene expression is dominated by MCP-1 expression. MCP-1
      mRNAs were also quantified by real-time-PCR (LightCycler). The behavior of cells
      studied after T. gondii infection was different (invasion and growth) and the
      cell mechanisms of chemokine regulation could be dependent on the type of cells
      infected, while MCP-1 may contribute to the cell recruitment during human
      cerebral reactivation of T. gondii.

PMID- 14722716
TI  - Accumulation of phosphorylated alpha-synuclein in the brain and peripheral
      ganglia of patients with multiple system atrophy.
AB  - We immunohistochemically examined the brain and peripheral sympathetic ganglia
      from eight patients with multiple system atrophy (MSA), using an antibody
      specific for phosphorylated alpha-synuclein (anti-PSer129). Phosphorylated alpha
      synuclein was deposited in five cellular locations: oligodendroglial cytoplasm
      and nucleus, and neuronal cytoplasm, processes and nucleus. Many neuronal
      cytoplasmic inclusions (NCIs) were found in the pontine and inferior olivary
      nuclei and, to a lesser extent, in the substantia nigra, locus ceruleus, and
      neocortical and hippocampal neurons. NCIs were also found in the sympathetic
      ganglia in two out of the eight cases. Moreover, anti-PSer129
      immunohistochemistry revealed extensive neuropil pathology; swollen neurites were
      abundant in the pontine nucleus, delicate neurites were observed in the deeper
      layers of the cerebral cortex and thalamus, and neuropil threads and dot-like
      structures were distributed in the basal ganglia and brainstem. Diffuse neuronal
      cytoplasmic staining (pre-NCI) was frequently found in the pontine and inferior
      olivary nuclei. Thus, the widespread accumulation of phosphorylated alpha
      synuclein in both glial and neuronal cells is a pathological feature in patients
      suffering from MSA.

PMID- 14722717
TI  - A disturbance of the gastric myoelectric activity in post-operative patients with
      biliary atresia.
AB  - BACKGROUND: Abnormalities in gastrointestinal motility have been reported in
      adult patients with advanced liver disease. However, there have so far been no
      reports on the gastric myoelectric activity in post-operative patients with
      biliary atresia (BA). AIM: The purpose of this study was to evaluate the gastric
      myoelectric activity in post-operative patients with BA in relation to liver
      fibrosis. PATIENTS AND METHODS: Twenty-one post-operative patients with BA,
      consisting of 6 boys and 15 girls with a mean age of 8.0 years and 6 healthy
      children (control group) were included in the study. The gastric myoelectric
      activity was measured by electrogastrography (EGG). The patients with BA were
      divided into two groups according to the serum hyaluronic acid (HA) level as a
      marker of liver fibrosis: the fibrotic group (FG, n=11), HA>50 ng/ml and the non
      fibrotic group (NF, n=10), HA <==50 ng/ml. All recorded data were spectrally
      analyzed and any parameters related to changes in the dominant peak frequency
      (DPF) and its power were investigated. Furthermore, the gastrointestinal symptom
      scores (GSS) were calculated in patients with dyspeptic symptoms according to the
      degree of advanced liver fibrosis. RESULTS: The results showed that 1) the
      postprandial DPF in the FG tended to be higher than that in the NFG ( p=0.051),
      2) the postprandial variability index of the DPF in the FG and NFG were
      significantly higher than those in the controls ( p<0.05), and 3) the preprandial
      percentage of normal waves (PNW) in the FG tended to be lower than that in the
      controls ( p=0.089). The postprandial PNWs in the FG and NFG were significantly
      lower than those in the controls ( p<0.05). Especially, the postprandial PNW in
      the FG was significantly lower than that in the NFG ( p<0.05). 4) The power ratio
      in the FG and NFG were significantly lower than those in the controls ( p<0.05),
      and 5) the GSSs in the FG were significantly higher than those in the NFG (
      p<0.05). CONCLUSIONS: The gastric myoelectric activity appeared to be disturbed
      in BA patients associated with portal hypertension and neurohormonal changes due
      to liver fibrosis.

PMID- 14722718
TI  - Peter Paul Rickham.

PMID- 14722719
TI  - Frontal intraparenchymal schwannoma: an unusual presentation.
AB  - CASE REPORT: A 13-year-old male with an 11-year history of a seizure disorder
      presented with recent onset raised intracranial pressure symptoms and no obvious
      phakomatosis. CT revealed a heterogeneous, frontal, intra-axial, densely
      enhancing, solid lesion with intense perilesional oedema and mass effect. Total
      microsurgical excision resulted in cure. Histopathological examination showed
      characteristic Antoni A and B areas and occasional Verocay bodies consistent with
      the diagnosis of an intraparenchymal schwannoma. DISCUSSION: The authors present
      a very rare, entirely solid manifestation of this highly uncommon lesion seen
      mostly in young adults and children with symptoms suggestive of raised
      intracranial pressure and associated seizure disorders. The possible
      developmental origins are discussed.

PMID- 14722720
TI  - Solitary myofibromatosis of the skull: a case report and review of literature.
AB  - CASE REPORT: We present a case of solitary myofibromatosis of the skull in a 4
      year-old girl. Surgery was performed and the final diagnosis of myofibromatosis
      was made histopathologically. DISCUSSION: Solitary myofibromatosis of the skull
      is rare and we found approximately 20 reported cases in the English-language
      literature. We reviewed eight well-described cases. CONCLUSION:
      Neuroradiologically, common features such as a lytic lesion with a sclerotic rim
      on roentgenogram and intra-diploic lesion with periosteal new bone formation both
      in the outer and inner table of the skull on computed assisted tomography are
      noticed.

PMID- 14722721
TI  - Turtles (Chelodina longicollis) regulate muscle metabolic enzyme activity in
      response to seasonal variation in body temperature.
AB  - Fluctuations in the thermal environment may elicit different responses in
      animals: migration to climatically different areas, regulation of body
      temperature, modification of biochemical reaction rates, or assuming a state of
      dormancy. Many ectothermic reptiles are active over a range of body temperatures
      that vary seasonally. Here we test the hypothesis that metabolic enzyme activity
      acclimatises seasonally in freshwater turtles (Chelodina longicollis) in addition
      to, or instead of, behavioural regulation of body temperatures. We measured body
      temperatures in free-ranging turtles (n = 3) by radiotelemetry, and we assayed
      phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and
      cytochrome c oxidase (CCO) activities in early autumn (March, n = 10 turtles),
      late autumn (May, n = 7) and mid-winter (July, n = 7) over a range of assay
      temperatures (10 degrees C, 15 degrees C, 20 degrees C, 25 degrees C). Body
      temperatures were either not different from, or higher than expected from a
      theoretical null-distribution of a randomly moving animal. Field body
      temperatures at any season were lower, however, than expected from animals that
      maximised their sun exposure. Turtles maintained constant PFK, LDH and CCO
      activities in different months, despite body temperature differences of nearly
      13.0 degrees C between March (average daily body temperature = 24.4 degrees C)
      and July (average = 11.4 degrees C). CS activity did not vary between March and
      May (average daily body temperature = 20.2 degrees C), but it decreased in July.
      Thus C. longicollis use a combination of behavioural thermoregulation and
      biochemical acclimatisation in response to seasonally changing thermal
      conditions. Ectothermic reptiles were often thought not to acclimatise
      biochemically, and our results show that behavioural attainment of a preferred
      body temperature is not mandatory for activity or physiological performance in
      turtles.

PMID- 14722722
TI  - Chromosome substitution strains: some quantitative considerations for genome
      scans and fine mapping.
AB  - A chromosome substitution strain (CSS) is an inbred strain in which one
      chromosome has been substituted from a different inbred strain by repeated
      backcrossing. A complete CSS set has one strain representing each chromosome
      against a uniform background, thus allowing genome-wide scans to be carried out
      for quantitative trait loci (QTLs) influencing any trait of interest. A one-way
      ANOVA by strain is first carried out, followed by planned comparisons using
      Dunnett's method. A QTL is detected and mapped to a chromosome when a significant
      difference is observed in a background strain vs CSS comparison. The most
      efficient ratio of background to CSS mice in any one comparison is 4.5:1, and the
      threshold for p <.05 genome-wide significance is estimated to be p =.003 to.004,
      a much less stringent criterion than any other mammalian mapping population. The
      use of false discovery rates tends to further reduce threshold stringency.
      Comparisons are made to the widely used conventional F(2) intercross, and both
      advantages and disadvantages are noted. The proportion of the trait variance due
      to a QTL is often much larger than the same QTL in an F(2), and the number of
      generations to attain fine mapping is greatly reduced. To serve as guidelines for
      planning experiments, methods to estimate sample sizes for QTL detection are
      presented for the initial genome scan and for subsequent fine mapping.

PMID- 14722724
TI  - X-linked and lineage-dependent inheritance of coping responses to stress.
AB  - Coping-or how one routinely deals with stress-is a complex behavioral trait with
      bearing on chronic disease and susceptibility to psychiatric disorders. This
      complexity is a result of not only underlying multigenic factors, but also
      important non-genetic ones. The defensive burying (DB) test, although originally
      developed as a test of anxiety, can accurately measure differences in coping
      strategies by assaying an animal's behavioral response to an immediate threat
      with ethological validity. Using offspring derived from reciprocal crosses of two
      inbred rat strains differing in DB behaviors, we provide convergent phenotypic
      and genotypic evidence that coping styles are inherited in an X-linked fashion.
      We find that first-generation (F(1)) males, but not females, show maternally
      derived coping styles, and second-generation (F(2)) females, but not males, show
      significant differences in coping styles when separated by grandmaternal lineage.
      By using a linear modeling approach to account for covariate effects (sex and
      lineage) in QTL analysis, we map three quantitative trait loci (QTL) on the X
      Chromosome (Chr) ( Coping-1, Approach-1, and Approach-2) associated with coping
      behaviors in the DB paradigm. Distinct loci were associated with different
      aspects of coping, and their effects were modulated by both the sex and lineage
      of the animals, demonstrating the power of the general linear modeling approach
      and the important interplay of allelic and non-allelic factors in the inheritance
      of coping behaviors.

PMID- 14722723
TI  - A strategy for the integration of QTL, gene expression, and sequence analyses.
AB  - Although hundreds if not thousands of quantitative trait loci (QTL) have been
      described for a wide variety of complex traits, only a very small number of these
      QTLs have been reduced to quantitative trait genes (QTGs) and quantitative trait
      nucleotides (QTNs). A strategy, Multiple Cross Mapping (MCM), is described for
      detecting QTGs and QTNs that is based on leveraging the information contained
      within the haplotype structure of the mouse genome. As described in the current
      report, the strategy utilizes the six F(2) intercrosses that can be formed from
      the C57BL/6J (B6), DBA/2J (D2), BALB/cJ (C), and LP/J (LP) inbred mouse strains.
      Focusing on the phenotype of basal locomotor activity, it was found that in all
      three B6 intercrosses, a QTL was detected on distal Chromosome (Chr) 1; no QTL
      was detected in the other three intercrosses, and thus, it was assumed that at
      the QTL, the C, D2, and LP strains had functionally identical alleles. These
      intercross data were used to form a simple algorithm for interrogating
      microsatellite, single nucleotide polymorphism (SNP), brain gene expression, and
      sequence databases. The results obtained point to Kcnj9 (which has a markedly
      lower expression in the B6 strain) as being the likely QTG. Further, it is
      suggested that the lower expression in the B6 strain results from a polymorphism
      in the 5'-UTR that disrupts the binding of at least three transcription factors.
      Overall, the method described should be widely applicable to the analysis of
      QTLs.

PMID- 14722725
TI  - Canine Imerslund-Grasbeck syndrome maps to a region orthologous to HSA14q.
AB  - Selective malabsorption of cobalamin (vitamin B(12)) accompanied by proteinuria,
      known as Imerslund-Grasbeck syndrome or megaloblastic anemia 1 (I-GS, MGA1; OMIM
      261100), is a rare autosomal recessive disorder. In Finnish kindreds, I-GS is
      caused by mutations in the cubilin gene ( CUBN), located on human Chromosome
      (Chr) 10. However, not all patients have CUBN mutations, and three distinct
      mutations in the amnionless gene, AMN, were very recently identified in patients
      from Norwegian and Israeli families. The present study demonstrates that in a
      large canine I-GS pedigree, the disease is genetically linked (peak multipoint
      LOD score 11.74) to a region on dog Chr 8 that exhibits conserved synteny with
      human Chr 14q. Multipoint analysis indicates that the canine disease gene lies in
      an interval between the echinoderm microtubule-associated, protein-like 1 ( EML1)
      gene and the telomere. A single critical recombinant further suggests that the
      disease gene is between markers in EML1 and the G protein-coupled receptor ( G2A)
      gene, defining an I-GS interval in the human genome that contains the AMN gene.
      Thus, these comparative-mapping data provide evidence that canine I-GS is a
      homologue of one form of the human disease and will provide a useful system for
      understanding the molecular mechanisms underlying the disease in humans.

PMID- 14722726
TI  - Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle,
      and deer.
AB  - Prions are proteins that play a central role in transmissible spongiform
      encephalopathies in a variety of mammals. Among the most notable prion disorders
      in ungulates are scrapie in sheep, bovine spongiform encephalopathy in cattle,
      and chronic wasting disease in deer. Single nucleotide polymorphisms in the sheep
      prion gene ( PRNP) have been correlated with susceptibility to natural scrapie in
      some populations. Similar correlations have not been reported in cattle or deer;
      however, characterization of PRNP nucleotide diversity in those species is
      incomplete. This report describes nucleotide sequence variation and frequency
      estimates for the PRNP locus within diverse groups of U.S. sheep, U.S. beef
      cattle, and free-ranging deer ( Odocoileus virginianus and O. hemionus from
      Wyoming). DNA segments corresponding to the complete prion coding sequence and a
      596-bp portion of the PRNP promoter region were amplified and sequenced from DNA
      panels with 90 sheep, 96 cattle, and 94 deer. Each panel was designed to contain
      the most diverse germplasm available from their respective populations to
      facilitate polymorphism detection. Sequence comparisons identified a total of 86
      polymorphisms. Previously unreported polymorphisms were identified in sheep (9),
      cattle (13), and deer (32). The number of individuals sampled within each
      population was sufficient to detect more than 95% of all alleles present at a
      frequency greater than 0.02. The estimation of PRNP allele and genotype
      frequencies within these diverse groups of sheep, cattle, and deer provides a
      framework for designing accurate genotype assays for use in genetic epidemiology,
      allele management, and disease control.

PMID- 14722727
TI  - Alternative splicing of the ovine CFTR gene.
AB  - Alternative splicing of the human CFTR gene was studied previously and shown not
      to generate functional CFTR-like chloride ion channels. However, it is possible
      that some of the alternatively spliced forms may encode CFTR proteins with
      different functions. The ovine CFTR gene is very similar to the human gene and
      has regulatory mechanisms in common. To evaluate whether the alternatively
      spliced forms of human CFTR are conserved in the sheep, the splice forms of the
      ovine CFTR gene were examined. A transcript lacking exon 9 was observed in the
      sheep, but unlike the human exon 9-transcript, it did not result from a
      polymorphic intron 8 splice acceptor site. Sheep CFTR transcripts lacking exon
      17b were seen and have also been described in the human. Transcripts lacking 98
      bp of the 5' end of exon 13, the whole of exon 13, and both exons 14b and 15
      respectively were seen in sheep but have not been reported in human. Splice site
      donor and acceptor sequences were isolated, and alternative transcripts were
      shown to result from a combination of aberrant sites and competition of 5' splice
      donor sequences.

PMID- 14722728
TI  - A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in
      dogs.
AB  - We undertook the biochemical and molecular characterization of hemophilia in a
      large pedigree of German wirehaired pointers. Males affected with hemophilia B
      had approximately 5% normal Factor IX coagulant activity and a proportional
      reduction of Factor IX protein concentration, indicative of a mild hemophilia B
      phenotype. Using Southern blot analyses and PCR amplification of genomic DNA, we
      discovered a large, 1.5-kb insertion in intron 5 of the Factor IX gene of an
      affected male. The insert consists of a 5' truncated canine Line-1 followed by an
      approximately 200-bp 3' poly (A) tract, flanked by a 15-bp direct repeat. The
      insert can be traced through at least five generations and segregates with the
      hemophilia B phenotype in this breed. This is the first description of a Factor
      IX mutation associated with mild hemophilia B in a non-human species and provides
      evidence for a recent Line-1 insertion event in the canine genome.

PMID- 14722729
TI  - Change of sonographic findings on cervical lymph nodes before and after
      preoperative radiotherapy.
AB  - The aim of this study was to assess the changes in the power Doppler sonographic
      findings in patients with oral cancer undergoing chemotherapy and radiotherapy.
      We performed US examinations on 187 cervical lymph nodes (71 metastatic and 116
      reactive nodes) excised from 52 patients before and after preoperative therapy.
      On Power Doppler images, we calculated the vascular index (VI) and evaluated the
      vascular pattern. We also assessed the diagnostic power using receiver operating
      characteristic (ROC) curve analysis. Irradiation caused an increase of the VI and
      better visualization of the vessels within the lymph node in the reactive nodes;
      however, in the metastatic nodes, the VI was not significantly different between
      that before and after irradiation. When the reader observed the images before
      irradiation, the area under an ROC curve (Az values) observed by B-mode
      sonography were closely similar to those obtained by B-mode plus power Doppler
      sonography. With both images before and after irradiation, the Az value obtained
      by B-mode plus power Doppler sonography was higher than that by B-mode sonography
      alone. After irradiation, the enhanced Doppler signals contributed to a better
      visualization of the vessels and a better detection of any vascular
      abnormalities.

PMID- 14722730
TI  - Management of patient dose and image noise in routine pediatric CT abdominal
      examinations.
AB  - The aim was to propose a strategy for finding reasonable compromises between
      image noise and dose as a function of patient weight. Weighted CT dose index
      (CTDI(w)) was measured on a multidetector-row CT unit using CTDI test objects of
      16, 24 and 32 cm in diameter at 80, 100, 120 and 140 kV. These test objects were
      then scanned in helical mode using a wide range of tube currents and voltages
      with a reconstructed slice thickness of 5 mm. For each set of acquisition
      parameter image noise was measured and the Rose model observer was used to test
      two strategies for proposing a reasonable compromise between dose and low
      contrast detection performance: (1) the use of a unique noise level for all test
      object diameters, and (2) the use of a unique dose efficacy level defined as the
      noise reduction per unit dose. Published data were used to define four weight
      classes and an acquisition protocol was proposed for each class. The protocols
      have been applied in clinical routine for more than one year. CTDI(vol) values of
      6.7, 9.4, 15.9 and 24.5 mGy were proposed for the following weight classes: 2.5
      5, 5-15, 15-30 and 30-50 kg with image noise levels in the range of 10-15 HU. The
      proposed method allows patient dose and image noise to be controlled in such a
      way that dose reduction does not impair the detection of low-contrast lesions.
      The proposed values correspond to high- quality images and can be reduced if only
      high-contrast organs are assessed.

PMID- 14722731
TI  - Experience with monthly, high-dose, intravenous immunoglobulin therapy in
      patients with different connective tissue diseases.
AB  - We aimed to investigate the efficacy and safety profile of high-dose intravenous
      immunoglobulin (HD-IVIG) therapy in patients with severe systemic lupus
      erythematosus (SLE), inflammatory muscle disease (IMD), Wegener's granulomatosis
      (WG), and/or concurrent infection who failed to respond to standard therapies. We
      evaluated the records of eight patients with SLE, eight with IMD, and four with
      WG who were treated with HD-IVIG (2 g/kg per month for 1-12 months) for active
      disease in 19 patients and concurrent infection in three (mycobacterial in two
      with SLE and cytomegaloviral in one with WG). Systemic lupus erythematosus
      disease activity index (SLEDAI) scores before and after HD-IVIG were
      statistically analysed. Remission was achieved in 14 cases (70%). The SLEDAI
      scores significantly decreased in patients with SLE (P=0.02). No serious side
      effect was observed. High-dose IVIG may be used as an adjunctive treatment in
      connective tissue diseases that do not respond to standard therapies or as
      alternative treatment for patients with concurrent severe infections or for whom
      immunosuppressives are contraindicated.

PMID- 14722732
TI  - Manometric assessment of esophageal motility in patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: The aim of this study was to assess the esophageal motility by
      manometry in patients with primary Sjogren's syndrome. METHODS: Esophageal
      manometry was carried out in 40 patients with primary Sjogren's syndrome (SS), 15
      with rheumatoid arthritis (RA), 15 with RA and secondary SS, and 21 healthy
      volunteers. RESULTS: We found that the mean lower esophageal sphincter (LES)
      pressures measured by station pull-through and rapid pull-through techniques were
      significantly higher in primary SS patients than with healthy controls and RA
      patients with or without SS (P<0.05). Our study did not show any major
      differences when comparing the three patient groups (P>0.05). However,
      peristaltic contraction velocity was lower and peristaltic contraction duration
      significantly higher at the middle and lower thirds of the esophagus in primary
      SS patients than in healthy controls (P<0.05). CONCLUSION: The results of our
      study support the view that various esophageal motility disorders can be found in
      patients with primary SS which could be related to an increase in LES pressure.
      We also found no correlation of the esophageal abnormalities with other factors
      studied, suggesting that the cause of dysphagia is multifactorial in nature.

PMID- 14722733
TI  - A cancer research (UK) randomized phase II study of idoxifene in patients with
      locally advanced/metastatic breast cancer resistant to tamoxifen.
AB  - Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had
      greater binding affinity for the oestrogen receptor (ER) and reduced agonist
      activity compared with tamoxifen in preclinical studies. In a randomized phase II
      trial in 56 postmenopausal patients with progressive locally advanced/metastatic
      breast cancer we assessed whether idoxifene showed evidence of activity compared
      with an increased 40 mg/day dose of tamoxifen in patients who had previously
      demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47
      patients eligible for response (25 idoxifene, 22 tamoxifen), two partial
      responses and two disease stabilizations (SD) for >6 months were seen with
      idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median
      duration of clinical benefit was 9.8 months. In contrast, no objective responses
      were seen with the increased 40 mg/day dose of tamoxifen, although two patients
      had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%).
      Idoxifene was well tolerated and the reported possible drug-related toxicities
      were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild
      nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar
      significant fall in serum follicle-stimulating hormone and luteinizing hormone
      after 4 weeks, together with a significant rise in sex hormone binding globulin
      levels and 11% reduction in serum cholesterol levels. In conclusion, while
      idoxifene was associated with only modest evidence of clinical activity in
      patients with tamoxifen-resistant breast cancer, its toxicity profile and effects
      on endocrine/lipid parameters were similar to those of tamoxifen.

PMID- 14722734
TI  - Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients
      with refractory solid malignancies.
AB  - PURPOSE: To determine the maximum tolerated dose and dose-limiting toxicities
      (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid
      tumors and to describe any preliminary antitumor activity associated with this
      regimen. MATERIALS AND METHODS: Patients received combination therapy with ZD9331
      as a 30-min infusion on days 1 and 8 of a 21-day cycle at doses of 100 or 130
      mg/m(2), followed by cisplatin at 50 or 75 mg/m(2) as a 30- to 60-min infusion on
      day 1 only. RESULTS: A total of 16 patients received 59 cycles of ZD9331 and
      cisplatin. Patients were enrolled at three dose levels: ZD9331/cisplatin 100/50 (
      n=3), 130/50 ( n=9), 130/75 ( n=4). DLTs at 130/75 included thrombocytopenia,
      neutropenia, fatigue, nausea, vomiting and stomatitis. Among 15 evaluable
      patients, 2 showed a partial response (patients with mesothelioma and head and
      neck cancer) and 6 showed stable disease (for a median of 5.5 cycles).
      CONCLUSIONS: ZD9331 in combination with cisplatin was well tolerated at a dose of
      130/50 mg/m(2) after establishing the principal DLTs of neutropenia and
      thrombocytopenia. The combination shows evidence of antitumor activity in a
      pretreated population.

PMID- 14722737
TI  - Primary cardiac T-cell lymphoma.
AB  - Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking
      cardiac disease, with the bulk of the tumor located intrapericardially, is
      extremely rare in immunocompetent patients. Clinical manifestations vary
      depending on sites of involvement in the heart and include chest pain,
      arrhythmias, pericardial effusion, and heart failure. Diagnosis is often
      difficult and may require invasive procedures; in some cases, diagnosis is not
      made until autopsy. Histologically, nearly all cases of PCL reported thus far
      have been of B-cell origin. In this report, we describe a case of PCL of T-cell
      origin in an adult immunocompetent patient, the second reported in the literature
      to the best of our knowledge, and provide a brief overview of the features of
      previously published PCL cases.

PMID- 14722738
TI  - Hydroxyurea in the treatment of major beta-thalassemia and importance of genetic
      screening.
AB  - Efforts have been undertaken to find an alternative approach to packed red cell
      transfusion (PRCT) in major beta-thalassemia. Augmentation of fetal hemoglobin
      (HbF) by hydroxyurea (HU) has been reported to be less effective in this
      condition as compared to sickle cell anemia due to molecular heterogeneity of the
      former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1
      mutation was evaluated in major beta-thalassemics. Forty-five patients, M/F ratio
      0.8, aged 6-33 years, received oral HU, 20 mg/kg per day, 4 days per week and
      daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine
      independent (group B). The aim was to stabilize or increase pre-PRCT Hb over
      10.0+/-0.5 g/dl and to reduce the need or cease the PRCT in group A and to
      increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly,
      facial bone deformity, in group B. HU was administered for at least 6 months
      (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1
      polymorphism and IVSII-1 mutation was carried out in most patients. In group A,
      25 patients have become PRCT independent for a period of 2.5-7.3 years (mean: 4
      years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8-13.7 g/dl),
      mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement
      was reduced in one patient, and ten patients did not respond. In group B HU has
      been given over 3.3 years (range: 2.8-4.8 years), Hb increased from 9.3 to
      10.4/dl, and there was no tangible progression of ineffective erythropoesis.
      Responders in both groups expressed more comfort with this regimen. Xmn1 and
      IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding
      patients. Molecular determination of genetic markers in early childhood will help
      to identify candidates for pharmacological HbF switching by HU.

PMID- 14722739
TI  - Diels-Alder reactivity of benzannulated isobenzofurans as assessed by density
      functional theory.
AB  - Density functional theory (DFT) calculations at the B3LYP/6-31G* level for
      isobenzofuran1 and eleven benzannulated derivatives of types2 and3 have been
      performed in order to compare their relative reactivities as dienes in Diels
      Alder reactions. The transition state (TS) energies for their reactions with
      ethylene have been determined and shown to form a linear correlation between
      activation energies and structure count (SC) ratios. TS energies as a method for
      comparison of diene reactivities can be applied to IBFs bearing substituents on
      the ring as well as those containing heteroatoms, for which the SC ratio method
      failed. Different measures of aromaticity of benzannulated IBFs indicated a
      decrease in aromaticity going from 4 to 14, which is also reflected in their
      reactivity as a dienes in Diels-Alder reaction.

PMID- 14722740
TI  - A computational approach to the synthesis of dirithromycin.
AB  - Dirithromycin is a macrolide antibiotic derived from erythromycin A.
      Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2
      (2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the
      condensation mechanism has been analyzed computationally by the AM1 method in the
      gas phase. First, the formation of the Schiff bases of dirithromycin and
      epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde
      were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and
      epidirithromycin were considered. Finally, the epimerization of the Schiff base
      of epidirithromycin to the Schiff base of dirithromycin was investigated. Our
      results show that, even though carbinolamine forms faster for epidirithromycin
      than the corresponding structure for dirithromycin, dirithromycin is the major
      product of the synthesis.

PMID- 14722741
TI  - Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure
      aqueous solution and urine.
AB  - Calcium oxalate (CaOx) is the most common component of human kidney stones.
      Heterogeneous nucleation is regarded as the key mechanism in this process. In
      this study, we have used an imprinted 6-methacrylamidohexanoic
      acid/divinylbenzene co-polymer as a biomimetic surface to nucleate CaOx crystal
      formation. The polymer was imprinted with either calcium oxalate monohydrate
      (COM) or dihydrate (COD) template crystals. These were washed out of the polymer,
      which was then immersed in various test solutions. The test solutions were an
      aqueous solution of calcium chloride and sodium oxalate, artificial urine and a
      sample of real urine. Crystals that formed on the polymer surface were
      characterized by X-ray powder diffraction, Fourier transform infrared
      spectroscopy, atomic absorption spectroscopy and scanning electron microscopy.
      Results showed that in the aqueous solution the COM-imprinted polymer induced the
      nucleation of COM. The COD-imprinted polymer induced only trace amounts of COD
      crystallization, together with larger quantities of COM. In artificial and real
      urines, COM also specifically precipitated on the COM-imprinted surface. The
      results show that, at least to some extent, the imprinted polymers direct
      formation of their morphologically matched crystals. In the case of COD, however,
      it appears that either rapid hydrate transformation of COD to COM occurs, or the
      more stable COM polymorph is directly co-precipitated by the polymer. Our results
      support the hypothesis that heterogeneous nucleation plays a key role in CaOx
      stone formation and that the imprinted polymer model could provide an additional
      and superior diagnostic tool for stone researchers to assess stone-risk in urine.

PMID- 14722742
TI  - Discovery of superoxide reductase: an historical perspective.
AB  - For more than 30 years, the only enzymatic system known to catalyze the
      elimination of superoxide was superoxide dismutase, SOD. SOD has been found in
      almost all organisms living in the presence of oxygen, including some anaerobic
      bacteria, supporting the notion that superoxide is a key and general component of
      oxidative stress. Recently, a new concept in the field of the mechanisms of
      cellular defense against superoxide has emerged. It was discovered that
      elimination of superoxide in some anaerobic and microaerophilic bacteria could
      occur by reduction, a reaction catalyzed by a small metalloenzyme thus named
      superoxide reductase, SOR. Having played a major role in this discovery, we
      describe here how the concept of superoxide reduction emerged and how it was
      experimentally substantiated independently in our laboratory.

PMID- 14722744
TI  - New insights on preventing and managing peritonitis.
AB  - Methods to prevent peritonitis are an essential component of any successful
      peritoneal dialysis (PD) program. Careful attention to training of the parents
      and child on the proper technique of PD and avoidance of manual spiking by using
      an assist device for the cycler, or use of the double-bag system for continuous
      ambulatory PD, should decrease risk of peritonitis from touch contamination.
      Secondly, reduction of peritonitis can be achieved through reduction of exit site
      infections by use of mupirocin antibiotic cream at the exit site of the PD
      catheter as part of routine care. If an exit site infection develops and is
      refractory to therapy, then the PD catheter can be successfully replaced as a
      single procedure, to reduce the risk of peritonitis. The third step in reducing
      the risk of peritonitis is to avoid repetitive episodes with the same organism.
      This may again involve replacing the catheter; as long as the effluent can be
      cleared, this again can be performed as a single procedure, thus allowing the
      child to avoid the trauma of hemodialysis. The focus in pediatric PD programs
      must always be on preserving the peritoneal membrane, and not on preservation of
      the catheter. With careful attention, peritonitis can become an uncommon event.

PMID- 14722747
TI  - Threat of predation negates density effects in larval gray treefrogs.
AB  - While density-dependence is central to most theory regarding population
      regulation and community structure, specific mechanisms that modify its effects
      in the absence of changes in consumer-resources ratios (e.g., thinning) are not
      well understood. To determine if the threat of predation alters effects of
      density, we investigated the interaction between density of larval treefrogs
      (Hyla chrysoscelis) and the non-lethal presence of a predatory fish (Enneacanthus
      obesus). A significant density by fish interaction was consistent for all
      response variables (e.g., larval survivorship, mass, and time to metamorphosis)
      driven by a complete lack of density effects in the presence of predators, while
      predator-free tanks showed classic density-dependent responses. Given that female
      H. chrysoscelis strongly avoid ovipositing in ponds containing fish, certain
      larval adaptations are apparently not constrained by maternal behavior and
      suggest redundancy in response to predators. Our data suggest that non-lethal
      effects of predators can determine larval performance irrespective of larval
      density, and that the non-lethal effects of predators can be strong whether
      lethal effects are strong or weak.

PMID- 14722748
TI  - Nutmeg mannikins ( Lonchura punctulata) reduce their feeding rates in response to
      simulated competition.
AB  - Group feeding animals experience a number of competitive foraging costs that may
      result in a lowered feeding rate. It is important to distinguish between
      reductions in feeding rates that are caused by reduced food availability and
      physical interactions among foragers from those caused by the mere presence of
      foraging companions that may be self-imposed in order to obtain some benefit of
      group membership. Starlings ( Sturnus vulgaris) reduce their feeding rates when
      in the company of simulated competitors located in an adjacent cage that cannot
      affect the food availability or interact with the forager. In the present study,
      we investigate whether the presence of simulated competitors in another species
      of passerine, nutmeg mannikins ( Lonchura punctulata), can result in self-imposed
      reductions in feeding rates. When feeding in the company of simulated
      competitors, mannikins spent more non-foraging time near them, fed more slowly,
      reduced travel times between patches, reduced their scanning time and pecked more
      slowly. These results provide evidence that simulated competitors induce a
      reduction in pecking rate: behavioural interference. These self-imposed responses
      to competitors may have resulted from attempts to remain close to the non-feeding
      companions. Such self-imposed reductions in feeding rates may be a widespread yet
      generally unrecognised foraging cost to group feeding individuals.

PMID- 14722749
TI  - An immunocytochemical study of pulpal responses to cavity preparation by laser
      ablation in rat molars by using antibodies to heat shock protein (Hsp) 25 and
      class II MHC antigen.
AB  - Initial responses of odontoblasts and immunocompetent cells to cavity preparation
      by laser ablation were investigated in rat molars. In untreated control teeth,
      intense heat shock protein (Hsp) 25 immunoreactivity was found in the cell bodies
      of odontoblasts, whereas cells immunopositive for the class II major
      histocompatibility complex (MHC) antigen were predominantly located beneath the
      odontoblast layer in the dental pulp. Cavity preparation caused the destruction
      of the odontoblast layer and the shift of most class-II-MHC-positive cells from
      the pulp-dentin border toward the pulp core at the affected site. Twelve hours
      after cavity preparation, numerous class-II-MHC-positive cells appeared along the
      pulp-dentin border and extended their processes deep into the exposed dentinal
      tubules, but subsequently disappeared from the pulp-dentin border together with
      Hsp-25-immunopositive cells by 24 h after the operation. By 3-5 days
      postoperation, distinct abscess formation consisting of polymorphonuclear
      leukocytes was found in the dental pulp. The penetration of masses of oral
      bacteria was recognizable in the dentinal tubules beneath the prepared cavity.
      These findings indicate that cavity preparation by laser ablation induces
      remarkable inflammation by continuous bacterial infections via dentinal tubules
      in this experimental model, thereby delaying pulpal regeneration.

PMID- 14722750
TI  - Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct
      closure and ventricular dilatation in H-Tx rat hydrocephalus.
AB  - The H-Tx rat has fetal-onset hydrocephalus associated with closure of the
      cerebral aqueduct and a reduction in the secretory cells of the subcommissural
      organ (SCO), a circumventricular organ situated in the dorsal wall of the
      cerebral aqueduct. The objective of this study was to determine the role of the
      SCO in hydrocephalus pathogenesis. Serial brain sections through aqueduct regions
      containing the SCO from H-Tx rats, together with non-hydrocephalic Fischer F344
      rats, were studied at E16, before hydrocephalus onset, at E17, the beginning of
      onset, and at P0 when the hydrocephalus was overt. Tissues were immunostained by
      AFRU, an antibody against the SCO glycoprotein, and for the intermediate filament
      nestin. The area of SCO cells with AFRU immunostaining and the severity of
      lateral ventricle dilatation were quantified by image analysis. At E16 all
      fetuses had distinct SCO ependymal cells, open aqueducts and normal lateral
      ventricles. The H-Tx fetuses fell into two groups with large areas and small
      areas of AFRU immunoreactivity, all with a full complement of SCO cells. By E17,
      fetuses with small areas of immunoreactivity had reduced numbers of tall SCO
      secretory cells, and most had aqueducts closed posteriorly and dilated
      ventricles. Three additional fetuses with small areas of immunoreactivity had
      narrow but patent aqueducts and normal ventricles, and another had an open
      aqueduct and dilated ventricles. At P0, pups previously identified as
      hydrocephalic had small areas of AFRU immunoreactivity, an aqueduct that was
      closed anteriorly but open posteriorly, ventricular dilatation, and an absence of
      SCO secretory cells. The aqueduct even when closed was lined by typical ependymal
      cells throughout. Decreased nestin immunostaining accompanied the SCO changes. It
      is concluded that reduced SCO glycoprotein immunoreactivity precedes both
      aqueduct closure and expansion of the lateral ventricles in the H-Tx rat.

PMID- 14722751
TI  - Ectopic localization of putative AII amacrine cells in the outer plexiform layer
      of the developing FVB/N mouse retina.
AB  - The FVB/N mouse is a model of retinitis pigmentosa which shows a rapid loss of
      photoreceptors during early postnatal (P) life. We investigated the cellular
      localization of glycine transporter 1 (GlyT-1) in the developing FVB/N mouse
      retina. In control retinas, the developmental pattern of GlyT-1-immunoreactive
      amacrine cells was well in accordance with a previous report. However, in the
      FVB/N mouse retina, some GlyT-1-labeled amacrine cells sent their processes into
      the outer plexiform layer (OPL) from P14 onward. From P21 onward, GlyT-1-labeled
      cells were visible in the OPL. These cells were further characterized by double
      label immunofluorescence experiments with an antiserum against disabled 1 (Dab
      1), and showed Dab-1 immunoreactivity, indicating that these cells are putative
      AII amacrine cells. These results clearly demonstrate that AII amacrine cells
      have the potential capacity to respond to photoreceptor degeneration by migrating
      or sprouting their processes into the OPL in the developing FVB/N mouse retina.

PMID- 14722754
TI  - The assertion that a G21V mutation in AGTR2 causes mental retardation is not
      supported by other studies.

PMID- 14722756
TI  - Tritrichomonas foetus pseudocysts adhere to vaginal epithelial cells in a contact
      dependent manner.
AB  - Tritrichomonas foetus is a parasitic protist of the urogenital tract of cattle.
      It presents the trophozoite stage, a motile elongated form that constitutes most
      of the cells in a normal population, and a pseudocyst stage, an immotile rounded
      form that appears under unfavourable environmental conditions. In the present
      report pseudocysts were studied in natural conditions and after induction by
      chemicals or cycles of cooling and warming of cultures. The capacity of T. foetus
      to adhere to vaginal epithelial cells (VECs) was compared for both trophozoite
      and pseudocyst forms. By the use of video-enhanced-contrast microscopy, scanning
      and transmission electron microscopy, and immunofluorescence microscopy
      techniques, we present evidence that: (1) T. foetus easily internalizes the
      flagella and forms pseudocysts under several unfavourable conditions; (2) T.
      foetus in both pseudocyst and trophozoite forms is able to adhere to VECs; (3)
      the adhesion rate is higher for pseudocysts than for trophozoites; (4) the
      adhesin Tf190 is expressed in both forms during interaction; (5) the adhesion
      process of pseudocysts seems to occur in a contact-dependent manner. Thus, we
      propose that the pseudocyst stage is not a degenerative form, but a functional
      life form that is able to interact with and firmly adhere to VECs.

PMID- 14722757
TI  - Characterisation and differentiation of pathogenic and non-pathogenic
      Acanthamoeba strains by their protein and antigen profiles.
AB  - Free-living amoebae of the genus Acanthamoeba are the causative agents of
      Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis. Acanthamoebae
      occur ubiquitously in the environment and are thus a constant cause of antigenic
      stimulation. In a previous study we have shown that compared to control sera, AK
      patients exhibit markedly lower immunoreactivities to whole cell antigen of
      Acanthamoeba spp. As the pathogenicity of acanthamoebae primarily relies on the
      excretion of proteins, it was the aim of the present study to investigate the
      immunoreactivity of metabolic antigen from different Acanthamoeba strains of
      varying pathogenicity. Three Acanthamoeba strains, one highly pathogenic, one non
      pathogenic but thermophilic and one non-thermophilic non-pathogenic, were used
      for antigen extraction. The antigen was harvested before and after contact with
      human cells and all strains were tested with AK sera and with sera from healthy
      individuals. It was shown that the somatic protein profiles of the Acanthamoeba
      strains correlated to the morphological groups, and that within morphological
      group II-the group associated with AK-the profiles of the metabolic antigens
      correlated to strain pathogenicity. Moreover, it was shown that the control sera
      showed markedly higher immunoreactivities than the sera of the AK patients and
      that this immunoreactivity was generally higher to the non-pathogenic strains
      than to the pathogenic strain. Altogether our results once again raise the
      question of whether there is an immunological predisposition in AK. To our
      knowledge this is the first study on the immunoreactivity of metabolic antigen of
      acanthamoebae.

PMID- 14722758
TI  - The Tibetan hare Lepus oiostolus: a novel intermediate host for Echinococcus
      multilocularis.
AB  - Multicystic hydatids have been found in the livers of hares ( Lepus oiostolus)
      examined from the Qinghai-Tibet plateau of China. In this study, the causative
      species was definitively identified as Echinococcus multilocularis by
      mitochondrial DNA sequencing. This is the first confirmation of larval E.
      multilocularis from hares. The hydatids contained protoscolices, suggesting that
      the hare may contribute to the transmission of E. multilocularis on the Tibetan
      plateau.

PMID- 14722759
TI  - Effects of tonicity on the release of neutral lipids in Echinostoma caproni
      adults and observations on lipids in excysted metacercariae.
AB  - High performance thin layer chromatography was used to analyze neutral lipids in
      worm incubates isotonic, hypotonic, and hypertonic to the intestinal habitat of
      adult Echinostoma caproni. Qualitative analysis revealed the presence of free
      sterols, free fatty acids, triacylglycerols, and a steryl ester/hydrocarbon
      fraction in all incubate samples. The most abundant neutral lipid fraction
      released into the incubation medium was the triacylglycerol fraction. This
      fraction was quantified after worms were maintained for 2 h at 37.5 degrees C in
      hypertonic (Locke's 2x solution), isotonic (Locke's 0.5x solution) and hypotonic
      (deionized water) media. Percentages of triacylglycerols on a wet-weight basis
      found in Locke's 2x, 0.5x, and deionized water were 0.369, 3.23, and 0.242,
      respectively, suggesting that the optimal medium to obtain maximal excretory
      secretory products is the Locke's 0.5x solution. Histochemical staining of whole
      excysted metacercariae with oil red O did not detect neutral lipids. Analysis of
      500 excysted metacercariae incubated for 2 h at 37.5 degrees C revealed that free
      sterols, free fatty acids, and triacylglycerols were released in amounts of 16.2,
      1.59, and 5.34 ng/organism, respectively. Our results were compared with previous
      studies on neutral lipids in excysted metacercariae and adults of E. trivolvis.
      Variations in the results of our study compared with others reflect intrinsic
      differences in the species of echinostome used.

PMID- 14722760
TI  - Application of the recombinant Theileria annulata surface protein in an indirect
      ELISA for the diagnosis of tropical theileriosis.
AB  - The recombinant surface protein of Theileria annulata (TaSP) was used in the
      standardization and validation of an enzyme linked immunosorbent assay (ELISA)
      for the detection of circulating antibodies against tropical theileriosis. ELISA
      data were expressed as the percentage positivity (PP) of the reactivity of an
      internal positive control. A total of 50 sera samples from a disease-free area
      were used for the calculation of the cut-off value which served as a threshold
      between the positive and the negative sera samples. This was determined as the
      mean PP plus two standard deviations or the twice the mean PP of the results
      obtained with these negative samples. The obtained thresholds were 17.8% and
      18.3%, respectively. Accordingly, the reactivity of 140 field sera samples
      collected at random from an area known to be endemic for tropical theileriosis in
      Sudan was determined as PP values which were then compared to the results
      obtained using the indirect fluorescence antibody test (IFAT) from the same
      samples. Both tests showed a high degree of correlation. The TaSP-ELISA had a
      sensitivity of 99.1% and specificity of 90.47% when taking the IFAT as a
      reference test. Our test has proved its suitability for the diagnosis of tropical
      theileriosis and could be used in serological surveys to map out the prevalence
      of the disease or to monitor vaccination efficiencies in disease-free
      populations.

PMID- 14722761
TI  - Mercury intoxication resulting from school barometers in three unrelated
      adolescents.
AB  - Three adolescents with severe hypertension due to mercury intoxication are
      presented. Two of them had skin rash, signs and symptoms of central nervous
      system involvement, peripheral neuropathy and mild-to-moderate proteinuria in
      addition to hypertension. All three patients had a history of exposure to
      mercury, the source being broken barometers taken from school laboratories 2-4
      months previously. Urine and blood mercury levels were consistent with mercury
      intoxication. The patients were treated with chelation therapy. One of them died;
      the others recovered over a period of 1-4 months. CONCLUSION: mercury
      intoxication should be considered in any child with signs and symptoms of
      hypertension, skin rash, peripheral neuropathy and behavioural changes. The
      parents and school administrators, as well as paediatricians, should be aware of
      the potential risks of mercury and should be encouraged to avoid mercury
      containing devices in schools and households.

PMID- 14722762
TI  - Viral heart disease: molecular diagnosis, clinical prognosis, and treatment
      strategies.
AB  - Myocarditis is considered as a potent predisposing factor for dilated
      cardiomyopathy (DCM). Molecular biological proof of viral genome and
      immunohistochemical evaluation of intramyocardial inflammation are substantial in
      the identification and diagnosis of this pathological condition. Viruses are
      generally thought to be the common causative agents that trigger myocarditis and,
      therefore, several investigations are indispensable for the detection of viral
      genome in the myocardium in diagnosing viral myocarditis. The era of molecular
      diagnosis for viral myocarditis began with the establishment of the slot blot
      hybridization technique for the detection of viral genome in endomyocardial
      biopsy specimens. Due to inherent technical inadequacies, this method soon was
      replaced by in situ hybridization and polymerase chain reaction (PCR). Although
      in situ hybridization combines both morphological and molecular diagnosis,
      difficulty in standardization, possibility of nonspecific hybridization, and
      focal viral infection have led PCR to be an ideal molecular diagnostic strategy
      for the detection of viral myocarditis. Despite controversies over the
      specificity of this technique, several studies have substantiated the use of PCR
      in virological diagnosis. The ability to detect the state of viral replicative
      activity by demonstrating the presence of enteroviral minus-strand RNA has added
      a new dimension to studies on viral etiology of myocarditis and DCM. Advances in
      molecular diagnosis have indicated beyond doubt that persistence of viral
      infection is associated with disease deterioration and poor prognosis. Viral
      etiology of myocarditis and its contribution to the development of DCM have
      suggested antiviral therapy for myocarditis and DCM patients with proven viral
      infection.

PMID- 14722763
TI  - Molecular and clinical characteristics of respiratory syncytial virus infections
      in hospitalized children.
AB  - The objective of this study was to determine the importance of respiratory
      syncytial virus (RSV) for hospitalization in the north east of Germany and to
      obtain molecular epidemiological data of the circulating strains. Using a rapid
      and sensitive reverse transcriptase-PCR, it was found that a quarter of pediatric
      respiratory disease admissions were due to RSV. Infections caused by RSV in
      hospitalized patients were determined over the whole year. Both RSV groups A and
      B were identified with a predominance of RSV A (86%) over the entire period. The
      analysis of the deduced amino acid sequences by direct sequencing showed that
      very similar RSV strains are circulating in the community.

PMID- 14722764
TI  - Chondroid lipoma is characterized by t(11;16)(q13;p12-13).

PMID- 14722765
TI  - Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas
      possibly related to autoimmune pancreatitis: an immunohistochemical and molecular
      analysis.
AB  - Inflammatory pseudotumors (IPT), also known as inflammatory myofibroblastic
      tumors (IMT), are benign inflammatory processes that may have an infectious
      etiology and are very rare in the pancreatico-biliary region. Recent studies
      suggest a biological distinction between IPT and IMT, the latter being a true
      neoplastic process. We describe a case of pancreatic IPT, originally diagnosed as
      malignancy, which presumably recurred 4 months after the operation.
      Histologically, the tumor consisted of a smooth muscle actin and CD68-positive
      spindle cell population and a more abundant mononuclear inflammatory cell
      population, primarily composed of macrophages and T-lymphocytes. Inflammatory
      cells were the source of connective tissue growth factor and transforming growth
      factor-beta1 and tended to accumulate around nerves and blood vessels, as well as
      around residual pancreatic parenchymal elements, where an intense angiogenetic
      response was detected. Comparative genomic hybridization analysis of the tumor
      showed no chromosomal imbalances. Polymerase chain reaction-based analysis of T
      cell receptor gamma gene rearrangement revealed an oligoclonal pattern. These
      findings suggest that the pathogenesis of aggressive cases of IPT could be
      related to the development of an intense and self-maintaining immune response,
      with the emergence of clonal populations of T-lymphocytes. The relation of the
      pancreatic IPT to autoimmune pancreatitis is emphasized.

PMID- 14722766
TI  - Immunohistochemical detection of human small lymphatic vessels under normal and
      pathological conditions using the LYVE-1 antibody.
AB  - The spread of tumor cells via lymphatic vessels to the lymph nodes is an
      important indicator of malignancy. However, previous markers used to identify
      lymphatic endothelium gave ambiguous results in immunohistochemical analyses with
      paraffin-embedded tissues. In this study, we attempted to prepare a polyclonal
      antibody against human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE
      1) for detecting lymphatic vessels using immunohistochemistry. The antibody was
      raised against a region near the transmembrane anchor of LYVE-1 in New Zealand
      white rabbits. Immunostainings with anti-LYVE-1 and von Willebrand factor
      antibodies were performed in various normal and pathological tissues. LYVE-1
      expression was confined to the endothelial surface of lymphatic vessels but was
      not found in the endothelium of blood vessels, which were positive for von
      Willebrand factor. Our LYVE-1 polyclonal antibody was useful for the
      identification of small lymphatic vessels in normal human tissues. In addition,
      the immunostaining enabled us to distinguish lymphatic invasion by malignant
      tumor cells from blood vessel invasion using paraffin-embedded sections. In
      conclusion, our polyclonal antibody against the transmembrane anchor of the
      peptide can be used to detect human lymphatic vessels under various conditions.

PMID- 14722767
TI  - Diagnostic relevance of Langerin detection in cells from bronchoalveolar lavage
      of patients with pulmonary Langerhans cell histiocytosis, sarcoidosis and
      idiopathic pulmonary fibrosis.
AB  - The diagnosis of pulmonary Langerhans cell histiocytosis might be refined by
      demonstrating reliability of a new cell marker, i.e., Langerin (CD207), used on
      bronchoalveolar lavage fluid. For this purpose, we collected material from
      patients with this disease and also with sarcoidosis and idiopathic pulmonary
      fibrosis as controls. In addition to the immunocytochemical detection of
      Langerin, we examined the expression profiles of CD1a and the macrophage tandem
      repeat mannose receptor (CD206). To test accessibility of Langerin, a C-type
      lectin, for mannosides, we employed reverse lectin histochemistry using mannose
      containing neoglycoproteins. The analysis revealed a significantly increased
      percentage of CD1a- and Langerin-positive cells in pulmonary Langerhans cell
      histiocytosis in comparison with both other studied diseases. No expression of
      the 175-kDa mannose-binding lectin (CD206) in Langerhans cells was observed.
      Evidently, binding sites on the cells were not accessible for the mannose
      containing neoglycoligand. These results provide evidence for the usefulness of
      Langerin-directed immuno- and glycohistochemical monitoring of bronchoalveolar
      lavage fluid in the diagnosis of pulmonary Langerhans cell histiocytosis.

PMID- 14722768
TI  - Highly restricted BMP10 expression in the trabeculating myocardium of the chick
      embryo.
AB  - Bone morphogenetic proteins (BMPs) control the development of diverse tissues
      during embryogenesis. Here, we report the expression of the BMP10 gene during
      chick development. BMP10 transcription is confined to the myocardium of atriae
      and ventricles in the forming heart from day 2 of development onwards (stage
      HH13). It correlates with the thickening of the innermost layer of the walls,
      i.e. the formation of myocardial ridges or trabeculae.

PMID- 14722769
TI  - Typography and color: effects of salience and fluency on conscious recollective
      experience.
AB  - Within one experiment the central assumptions of the distinctiveness/fluency
      account of recollective experience were tested and contrasted with predictions of
      processing theory. To manipulate perceptual salience, the typography of words was
      varied. Effects of conceptual salience were induced by a variation of word color.
      In the study phase participants generated different word or object images
      according to presented words. To manipulate perceptual and conceptual fluency one
      test group underwent a priming procedure in the test phase, consisting of a
      recognition test, whereby some primes were identical to the target words
      typographically or by color and others were not. Additionally, all participants
      were asked to make judgments of recollective experience (remember, know, guess)
      after the old/new decisions. The results of the data analyses confirm the
      distinctiveness/fluency account. Words written in an unusual typography or color
      were judged significantly more often as "remembered" than normal words. The
      priming procedure uncovered some effects of fluency on reaction times: old/new
      decisions took less time if prime and target words were perceptually or
      conceptually identical.

PMID- 14722770
TI  - An auxin-inducible gene from loblolly pine (Pinus taeda L.) is differentially
      expressed in mature and juvenile-phase shoots and encodes a putative
      transmembrane protein.
AB  - We have isolated a gene from loblolly pine, 5NG4, that is highly and specifically
      induced by auxin in juvenile loblolly pine shoots prior to adventitious root
      formation, but substantially down-regulated in physiologically mature shoots that
      are adventitious rooting incompetent. 5NG4 was highly auxin-induced in roots,
      stems and hypocotyls, organs that can form either lateral or adventitious roots
      following an auxin treatment, but was not induced to the same level in needles
      and cotyledons, organs that do not form roots. The deduced amino acid sequence
      shows homology to the MtN21 nodulin gene from Medicago truncatula. The expression
      pattern of 5NG4 and its homology to a protein from Medicago involved in a root
      related process suggest a possible role for this gene in adventitious root
      formation. Homology searches also identified similar proteins in Arabidopsis
      thaliana and Oryza sativa. High conservation across these evolutionarily distant
      species suggests essential functions in plant growth and development. A 38-member
      family of genes homologous to 5NG4 was identified in the A. thaliana genome. The
      physiological significance of this redundancy is most likely associated with
      functional divergence and/or expression specificity of the different family
      members. The exact biochemical function of the gene is still unknown, but
      sequence and structure predictions and 5NG4::GFP fusion protein localizations
      indicate it is a transmembrane protein with a possible transport function.

PMID- 14722771
TI  - Loss of quantum yield in extremely low light.
AB  - It has generally been assumed that the photosynthetic quantum yield of all C3
      plants is essentially the same for all unstressed leaves at the same temperature
      and CO2 and O2 concentrations. However, some recent work by H.C. Timm et al.
      (2002, Trees 16:47-62) has shown that quantum yield can be reduced for some time
      after leaves have been exposed to darkness. To investigate under what light
      conditions quantum yield can be reduced, we carried out a number of experiments
      on leaves of a partial-shade (unlit greenhouse)-grown Coleus blumei Benth.
      hybrid. We found that after leaves had been exposed to complete darkness, quantum
      yield was reduced by about 60%. Only very low light levels were needed for
      quantum yield to be fully restored, with 5 micromol quanta m(-2) s(-1) being
      sufficient for 85% of the quantum yield of fully induced leaves to be achieved.
      Leaves regained higher quantum yields upon exposure to higher light levels with
      an estimated time constant of 130 s. It was concluded that the loss of quantum
      yield would be quantitatively important only for leaves growing in very dense
      understoreys where maximum light levels might not exceed 5 micromol quanta m(-2)
      s(-1) even in the middle of the day. Most leaves, even in understorey conditions,
      do, however, experience light levels in excess of 5 micromol quanta m(-2) s(-1)
      over periods where they obtain most of their carbon so that the loss of quantum
      yield would affect total carbon gain of those leaves only marginally.

PMID- 14722773
TI  - The mitochondrial outer membrane is not a major diffusion barrier for ADP in
      mouse heart skinned fibre bundles.
AB  - The response of mitochondrial oxygen consumption to ADP in saponin-skinned
      cardiac fibre bundles has an apparent Km an order of magnitude higher than that
      in isolated mitochondria. Here we report that incubating skinned cardiac fibre
      bundles from wild-type mice or double-knockout mice lacking both cytosolic and
      mitochondrial creatine kinase (CK) with CK and creatine or with yeast hexokinase
      and glucose as extramitochondrial ADP-producing systems decreases the apparent Km
      of the bundles for ADP severalfold. We conclude that the affinity of mitochondria
      for ADP in mouse heart is of the same order of magnitude as that of isolated
      mitochondria, while the high apparent Km of the bundles is caused by diffusion
      gradients outside the mitochondria.

PMID- 14722772
TI  - The SLC4 family of HCO 3 - transporters.
AB  - The SLC4 family consists of ten genes. All appear to encode integral membrane
      proteins with very similar hydropathy plots-consistent with the presence of 10-14
      transmembrane segments. At least eight SLC4 members encode proteins that
      transport HCO(3)(-) (or a related species, such as CO(3)(2-)) across the plasma
      membrane. Functionally, these eight proteins fall into two major groups: three Cl
      HCO(3) exchangers (AE1-3) and five Na(+)-coupled HCO(3)(-) transporters (NBCe1,
      NBCe2, NBCn1, NDCBE, NCBE). Two of the Na(+)-coupled HCO(3)(- )transporters
      (NBCe1, NBCe2) are electrogenic; the other three Na(+)-coupled HCO(3)(-)
      transporters and all three AEs are electroneutral. At least NDCBE transports Cl(
      ) in addition to Na(+) and HCO(3)(-). Whether NCBE transports Cl(-)-in addition
      to Na(+) and HCO(3)(-)-is unsettled. In addition, two other SLC4 members (AE4 and
      BTR1) do not yet have a firmly established function; on the basis of homology,
      they fall between the two major groups. A characteristic of many, though not all,
      SLC4 members is inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonate
      (DIDS). SLC4 gene products play important roles in the carriage of CO(2) by
      erythrocytes, the absorption or secretion of H(+) or HCO(3)(-) by several
      epithelia, as well as the regulation of cell volume and intracellular pH.

PMID- 14722774
TI  - The selectivity filter of the tandem pore potassium channel TASK-1 and its pH
      sensitivity and ionic selectivity.
AB  - We have studied pH sensitivity and ionic selectivity of the tandem pore K(+)
      channel TASK-1 heterologously expressed in Xenopus oocytes. We fit pH sensitivity
      assuming that only one of the two residues H98 need be protonated for channels to
      be shut. The effect of protons was weakly voltage dependent with a p K(a) of 6.02
      at +40 mV. Replacement of His (H98D, H98N) reduced pH sensitivity but did not
      abolish it. Use of a concatameric channel permitted replacement of one His
      residue only; this concatamer was fully pH-sensitive. Increasing the number of
      His residues to 4 (mutant D204H) abolished pH sensitivity over the physiological
      range. The implication that D204 plays a role in pH-sensitivity was confirmed by
      the finding that pH sensitivity over the physiological range was also abolished
      in the mutant D204N. Ionic selectivity was also altered in D204H, D204N and H98D
      mutants. P(Rb)/ P(K) was increased from 0.80+/-0.04 (n=19) in wild type to 1.06+/
      0.04 (n=19) in D204H. H98D, D204H and D204N were permeable to Na(+) with P(Na)/
      P(K)=0.39+/-0.03 (n=14) in H98D, 0.64+/-0.04 (n=18) in D204H and 0.33+/-0.07
      (n=3) in D204N. Thus, the arrangement of ring of residues HDHD appears to
      optimise both pH sensitivity and ionic selectivity.

PMID- 14722775
TI  - An in vitro investigation of aorta and corpus cavernosum from eNOS and nNOS gene
      deficient mice.
AB  - In order to ascertain the relative contribution of the endothelial and neuronal
      nitric oxide (NO) synthase isoforms on NO-dependent vascular and nerve function
      in vitro, aorta and corpus cavernosum from mice deficient in their expression
      (eNOS-/- and nNOS-/-) were isolated in organ baths for tension measurements.
      Agonist or electrical field stimulation (EFS) evoked nerve-mediated responses
      were compared against wild-type controls. In aortas from nNOS-/- mice,
      contraction responses to phenylephrine were increased. Conversely, endothelium
      dependent relaxation (EDR) to acetylcholine (ACh) was decreased. In contrast,
      eNOS-/- aortas showed decreased sensitivity to phenylephrine and developed a
      flurbiprofen-sensitive contraction to ACh, and sensitivity to the NO-donor sodium
      nitroprusside was increased. In cavernosum from eNOS-/- and nNOS-/- mice, maximum
      contractions to phenylephrine and EFS, and relaxation responses to nitroprusside,
      were increased. As in aorta, ACh addition led to a contractile response in eNOS-/
      cavernosum. Maximum EFS induced non-adrenergic, non-cholinergic (NANC) nerve
      mediated relaxation was increased in eNOS-/-, whilst being decreased in nNOS-/-
      cavernosum. These data suggest that whilst NO-dependent vascular function is
      primarily eNOS mediated, and nerve function nNOS mediated, aorta function may be
      at least partially reliant on nNOS-related mechanisms. In addition, mechanisms of
      physiological compensation were observed, which require further study.

PMID- 14722776
TI  - Nitric oxide inhibits arginine-vasotocin-induced increase of water osmotic
      permeability in frog urinary bladder.
AB  - The present study addressed the question of whether nitric oxide (NO)
      participates in regulation of osmotic water permeability in the urinary bladder
      of the frog Rana temporaria L. Experiments were carried out on isolated, paired
      hemi-bladders filled with amphibian Ringer solution diluted 1:10 with distilled
      water. Sodium nitroprusside (SNP, 125-250 micro M), an NO donor, markedly
      attenuated the increase of osmotic water flow elicited by arginine-vasotocin
      (AVT) (AVT 10(-10) M: 2.20+/-0.26; AVT plus 200 micro M SNP: 1.21+/-0.15 micro
      l/min cm(2), n=20, P<0.001). This effect of SNP was apparent only in the presence
      of 50 micro M zaprinast, an inhibitor of the cGMP-specific phosphodiesterase-5
      (PDE5). In the presence of zaprinast, SNP elevated cGMP production significantly
      both in control and AVT-stimulated urinary bladders, but had no effect on the
      level of cAMP (AVT 5 x 10(-10) M: 7.6+/-0.6; AVT plus SNP 200 micro M: 7.5+/-0.4
      pmol/mg protein, n=8, N.S.). 1 H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one
      (ODQ, 25-100 micro M), an inhibitor of soluble guanylate cyclase, enhanced the
      AVT-induced water flow, decreased the SNP-stimulated increase of cGMP in the
      bladder tissue and almost abolished the inhibitory effect of SNP on the AVT
      induced hydroosmotic response. 8-( p-Chlorophenylthio)-cGMP (8-pCPT-cGMP, 25 or
      50 micro M), a membrane-permeable cGMP analogue specific for cGMP-dependent
      protein kinase (PKG), inhibited, whereas 2 micro M KT-5823, an inhibitor of PKG,
      significantly stimulated the increase of water flow induced by AVT. The
      inhibitory effect of SNP on AVT-induced water flow was almost completely reversed
      by KT-5823, but not by 50-100 micro M erythro-9-[2-hydroxy-3-nonyl]adenine
      (EHNA), an inhibitor of cGMP-activated PDE2. Immunohistochemistry of urinary
      bladder slices with antibodies against different types of NO synthase (NOS)
      revealed a positive immunostaining for neuronal NOS (nNOS) in the mucosal
      epithelium. These results suggest that in the frog urinary bladder endogenous NO
      is involved in regulation of water osmotic permeability. NO inhibits the AVT
      induced increase of water flow at least partly by activation of PKG, which
      interferes with the hydroosmotic effect of AVT probably at (a) post-cAMP step(s).

PMID- 14722777
TI  - Validity of intra-operative neuromonitoring signals in thyroid surgery.
AB  - BACKGROUND: Although intra-operative neuromonitoring (IONM) is widely used in
      thyroid surgery, the validity of the received IONM signals are still unknown.
      METHOD: Prospective collection of data forms in 29 hospitals from 8,534 patients
      with 15,403 nerves at risk, who underwent surgery for benign and malignant goitre
      disorders between August 1999 and January 2001. IONM was performed by indirect
      stimulation via the vagal nerve and by direct recurrent laryngeal nerve (RLN)
      stimulation in 12,486 cases. IONM signals were compared with early (<14 days) and
      late (6 months) postoperative vocal cord function findings. RESULTS: The
      transient and permanent RLN palsy rate was 2.8% and 0.7%, respectively.
      Monitoring of the RLN function was significantly more reliable via the indirect
      IONM stimulation route than via the direct IONM stimulation route (specificity
      P<0.05). IONM by indirect stimulation via the vagal nerve reliably excluded
      postoperative, permanent, vocal cord palsy (specificity 97.6%, negative
      predictive value 99.6%). However, a changed IONM was insufficient to predict
      permanent RLN palsy (sensitivity 45.9%, positive predictive value 11.6%). IONM
      was not associated with increased general morbidity. CONCLUSIONS: For intra
      operative neuromonitoring, indirect stimulation of the RLN is superior to direct
      stimulation. An intact acoustic IONM signal is highly predictive of intact
      postoperative RLN function. When the IONM signal is abnormal or absent, a one
      stage extensive thyroid resection should be performed only if the surgeon is
      absolutely convinced that the first RLN is not harmed or a total thyroidectomy is
      mandatory.

PMID- 14722778
TI  - Reliability of erector spinae oxygenation and blood volume responses using near
      infrared spectroscopy in healthy males.
AB  - The purpose of this investigation was to (1). describe the trends in oxygenation
      (OXY) and blood volume (BV) of the right and left paraspinal muscles during the
      Biering-Sorensen muscle endurance (BSME) test using near infrared spectroscopy
      (NIRS), and (2). assess the test-retest reliability of OXY and BV changes during
      the BSME in healthy males. Seventeen healthy males [age=28.4 (9.8) years,
      height=1.75 (0.05) m, body mass=82.7 (9.1) kg; mean (SD)] completed two BSME
      trials within 1 week. NIRS probes were placed bilaterally at lumbar 3. The test
      was performed with the subject in the prone position using the following
      protocol: 2 min baseline, BSME, and 4 min recovery. The delta and range values of
      OXY and BV were used for analysis. Acceptable intra-class correlations were
      observed for endurance time and all the NIRS variables at the point of fatigue
      and at each 10% segment of the BSME during the two trials. Bland-Altman plots
      confirmed the reproducibility of the bilateral NIRS responses of the
      paravertebral muscles. The BV responses were more reliable than the OXY responses
      during the two trials. The OXY and BV responses of the paravertebral muscles
      during static contractions can be measured reliably using NIRS. Future studies
      should focus primarily on BV for analysis.

PMID- 14722779
TI  - Hormonal changes during long-term isolation.
AB  - Confinement and inactivity induce considerable psychological and physiological
      modifications through social and sensory deprivation. The aim of the SFINCSS-99
      experiment was to determine the cardiovascular and hormonal pattern of blood
      volume regulation during long-term isolation and confinement. Simulation
      experiments were performed in pressurized chambers similar in size to the volumes
      of modern space vehicles. Group I consisted of four Russian male volunteers, who
      spent 240 days in a 100-m(3 )chamber. Group II included four males (one German
      and three Russians) who spent 110 days in isolation (200-m(3) module). The blood
      samples, taken before, during and after the isolation period, were used to
      determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and
      osmolality levels. From the urine samples, electrolytes, osmolality, nitrites,
      nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and
      metanephrine levels were determined. The increase in plasma volume (PV) that is
      associated with a tendency for a decrease in plasma active renin is likely to be
      due to decreased sympathetic activity, and concords with the changes in urinary
      catecholamine levels during confinement. Urinary catecholamine levels were
      significantly higher during the recovery period than during confinement. This
      suggests that the sympathoadrenal system was activated, and concords with the
      increase in heart rate. Vascular resistance is determined by not only the
      vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in
      urine, as an indicator of nitric oxide release, did not reveal any significant
      changes. Analysis of data suggests that the duration of the isolation was a main
      factor involved in the regulation of hormones.

PMID- 14722780
TI  - Morphological damage in rabbit retina caused by subretinal injection of
      indocyanine green.
AB  - PURPOSE: To investigate the effects of subretinal indocyanine green (ICG) on
      retinal morphology in rabbit eyes. METHODS: Retinal bleb detachments were
      produced by injections of ICG at dosages of 25 mg/ml, 5 mg/ml, and 0.5 mg/ml or
      with an injection of balanced salt solution (BSS) into the subretinal space of
      albino rabbit eyes. Morphological change was assessed by light and transmission
      electron microscopy from the viewpoint of dose and time. Some sections were also
      probed with the TUNEL technique to detect apoptotic cells. RESULTS: At 14 days
      after subretinal injection of BSS and 0.5 mg/ml ICG, the structure of the retina
      was well preserved. However, injections of 5 mg/ml or 25 mg/ml caused thinning of
      the retina, especially loss of the outer retinal layer. In eyes injected with 5
      mg/ml ICG, the photoreceptors began disappearing within 3 days after the
      injection and over time showed the development of retinal atrophy. TUNEL-positive
      cells appeared abundantly in the photoreceptor layers 1 and 3 days after the
      injection of 5 mg/ml ICG. Transmission electron microscopy confirmed apoptosis in
      the photoreceptors. CONCLUSION: These data indicate that subretinal ICG induces
      apparent morphological damage of the retina in a dose-dependent manner.

PMID- 14722781
TI  - Reduction of retinal blood flow in high myopia.
AB  - PURPOSE: To investigate changes in retinal vessel diameter and blood velocity in
      high myopia using laser Doppler velocimetry. METHODS: Thirty-nine subjects (39
      eyes) were enrolled in the study. The subjects were divided into three groups
      according to their refractive status; 15 eyes (15 patients) with emmetropia
      (within +/-3.0 diopters), 14 eyes (14 patients) with mild myopia (between -3.0
      and -8.0 diopters), and 10 eyes (10 patients) with high myopia (>-8.0 diopters).
      Patient age was matched between groups. Blood velocity and vessel diameter of the
      upper or lower temporal retinal artery were measured using laser Doppler
      velocimetry with an eye-tracking system, and measurements were compared between
      groups. RESULTS: The average retinal blood flow and vessel diameter in highly
      myopic eyes were significantly decreased compared with emmetropic eyes or mild
      myopic eyes (Mann-Whitney U test, p<0.05). Also, there was significant difference
      regarding retinal blood flow and vessel diameter between eyes with mild myopia
      and the other groups. In addition, there was no significant difference in blood
      velocity between the three groups. CONCLUSIONS: Retinal blood flow was decreased
      in high myopia, mainly due to the narrowing of the retinal vessel diameter.
      Impaired retinal blood flow might have a role in the development of chorioretinal
      atrophy in high myopia.

PMID- 14722782
TI  - Differential expression of angioregulatory factors in normal and CNV-derived
      human retinal pigment epithelium.
AB  - BACKGROUND: Choroidal neovascularization (CNV) causes loss of vision in age
      related macular degeneration (AMD). In CNV, choroidal capillaries penetrate
      Bruch's membrane and the retinal pigment epithelium (RPE). Angiogenic factors
      produced by RPE cells are suspected as major contributors to CNV development. We
      therefore studied the differential expression of angioregulatory factors in
      normal and CNV-derived RPE. METHODS: Cultures of normal (ARPE-19) and CNV-derived
      RPE (CNV-RPE) were compared by quantitative PCR. Differential expression was
      verified on the protein level by immunohistochemistry in tissue samples. RESULTS:
      The angioregulatory factors VEGF-A, VEGF-B, VEGF-C, Angiopoietin-1 (Ang-1) and
      Angiopoietin-2, Semaphorin-3A, PEDF, HIF-1, FGF-2, and the receptors VEGF-R2,
      Neuropilin-1 and Neuropilin-2 were detected in both, ARPE-19 and CNV-RPE.
      Transcription of PEDF, FGF-2, Neuropilin-2, Ang-1 and Ang-2 was significantly
      upregulated in CNV-RPE. EphA7, VEGF-R1 and leptin were transcribed exclusively in
      CNV-RPE and Eph-A7 and VEGF-R1 proteins were present exclusively in CNV
      specimens. CONCLUSIONS: A set of common factors controlling angiogenesis was
      detected in both, ARPE-19 cells and CNV-RPE cells. Surprisingly, PEDF and other
      factors inhibiting angiogenesis are strongly upregulated in CNV-RPE; thus, at
      least in later stages, the RPE has a potential to control angiogenesis in age
      related macular degeneration.

PMID- 14722783
TI  - Visual extinction for motion.
AB  - PURPOSE: To alert clinicians to the heretofore undescribed visual behavioral
      phenomenon of visual extinction limited to motion. METHODS: Neuro
      ophthalmological, neuropsychological and neuroimaging assessment of a 57-year-old
      man with vague visual complaints. RESULTS: Extinction limited to visual motion
      perception in the left hemifield was demonstrated. The visual defect was
      attributed to a lesion involving the right occipito-temporo-parietal region in
      the presence of a left posterior infarction. CONCLUSION: The importance of
      clinical examination for detection of this specific higher-order visual defect is
      stressed. The present observation may be helpful in understanding the effects of
      attention on visual perception and may have important implications for
      rehabilitation of patients with visual neglect.

PMID- 14722784
TI  - Infections by the yeast Kodomaea (Pichia) ohmeri: two cases and literature
      review.
AB  - A 14-year-old boy who was neutropenic following chemotherapy for leukemia
      developed fungemia caused by the yeast Kodomaea ohmeri ( Pichia ohmeri). The
      infection was cured by catheter removal and the use of fluconazole. A 74-year-old
      man who had undergone surgeries for a subcutaneous tumor developed polymicrobic
      cellulitis involving Kodomaea ohmeri. Despite surgical debridement and antibiotic
      therapy, the patient died of complications. Including these 2 cases, there have
      been 10 Kodomaea ohmeri infections reported thus far, all occurring in patients
      with pre-existing conditions. There have been seven cases of fungemia and one
      case each of peritonitis, funguria, and cellulitis. The treatment employed varied
      depending on the site/source of infection. Seven patients recovered and three
      died. The microbiological data available suggest that Kodomaea ohmeri can be
      identified definitively by biochemical tests and is susceptible to amphotericin B
      and either susceptible to or dose dependently susceptible to itraconazole and
      fluconazole.

PMID- 14722798
TI  - Ethical, moral, and legal issues in speech and language pathology.

PMID- 14722800
TI  - Morality, ethics, and law: introductory concepts.
AB  - The purpose of this article is to differentiate morality, ethics, and law.
      Morality refers to a set of deeply held, widely shared, and relatively stable
      values within a community. Ethics as a philosophical enterprise involves the
      study of values, and the justification for right and good actions, as represented
      by the classic works of Aristotle (virtue ethics), Kant (duty-based ethics), and
      Bentham and Mill (utilitarian and consequentialist ethics). Applied ethics, in
      contrast, is the use of ethics principles (e.g., respect for autonomy,
      beneficence, and nonmaleficence, justice) in actual situations, such as in
      professional and clinical life. Finally, law is comprised of concrete duties
      established by governments that are necessary for maintaining social order and
      resolving disputes, as well as for distributing social resources according to
      what people need or deserve.

PMID- 14722801
TI  - Clinical ethics in the context of language and cognitive impairment: rights and
      protections.
AB  - Ethical dilemmas are particularly complex when a patient has a communication
      disorder. Questionable decision-making capacity can affect an individual's
      ability to participate in the informed consent process. When other cognitive
      impairments as well as language deficits are present, the risk of losing one's
      right to autonomy is greatly increased. Alternatively, the protection afforded
      those who are clearly incompetent may be limited if a person appears to have
      decision-making capacity but is unable to adequately process information. These
      challenges are illustrated in this article by use of clinical case descriptions.
      They also serve to demonstrate ways in which speech-language pathologists can
      provide the expertise needed to assist patients and medical teams in addressing
      these particular issues and ensuring patient autonomy.

PMID- 14722802
TI  - Ethical issues in dysphagia: when patients refuse assessment or treatment.
AB  - The primary goal of intervention for patients with dysphagia is to restore oral
      feeding. When patients are unable to achieve adequate nutrition, hydration, or
      safety with oral feeding, then nonoral approaches are often recommended. Although
      patients' rights to accept or refuse clinical recommendations are widely
      recognized, when a patient refuses tube feeding or other recommendations,
      dysphagia specialists are left with a host of practical questions about their
      role in caring for the patient. We review the criteria for assessing patients'
      capacity to make informed choices, approaches to decision making when patients
      lack capacity, and the roles and responsibilities of clinicians when patients
      choose high-risk treatment options.

PMID- 14722803
TI  - Clinical and professional ethics in the management of motor speech disorders.
AB  - The field of biomedical ethics is increasingly discussed in speech-language
      pathology graduate school curricula as well as in continuing education forums.
      The application of the principles of medical ethics can be extremely helpful to
      the difficult decisions sometimes facing speech-language pathologists with
      respect to doing good for their patients while respecting both patients' autonomy
      and federal and state law. Professions have increasing attempted to codify
      professional issues relating to moral issues through codes of ethics and codes of
      conduct. This article focuses on applying selected principles of medical ethics
      and professional codes of conduct to the practice of speech pathology specific to
      motor speech disorders. Case examples are provided to illustrate ethical decision
      making through consideration of the American Speech-Language-Hearing Association
      (ASHA) Code of Ethics as well as a number of principles of medical ethics.

PMID- 14722804
TI  - Ethical and legal issues related to telepractice.
AB  - The subject of speech-language pathologists providing services over a distance
      via telepractice is attracting the attention of the profession. The new service
      delivery model will challenge us to exploit its potential without violating legal
      constraints or compromising our affirmative ethical responsibilities. This
      article provides an overview of the implications of current state licensure laws
      on telepractice and a look at the issues of competence, standard of care,
      privacy, informed consent, and the use of support personnel. Several principles
      are offered to guide the practitioner and additional resources are suggested.

PMID- 14722805
TI  - Research ethics 101: the responsible conduct of research.
AB  - The ethical, responsible conduct of research (RCR) is fundamental to the quality
      of science in our discipline, and ultimately to the advancement of knowledge.
      Therefore, appreciation of the basic concepts of RCR is vital to all segments of
      the discipline, from students to clinicians to scientists themselves. Conversely,
      fraud in science, or research misconduct, is diametrically opposed to the quality
      of science and the advancement of knowledge. This article overviews the major
      concepts associated with RCR as well as the kinds of behaviors that would be
      identified as research misconduct. Case study examples are provided for
      contemplation and discussion.

PMID- 14722808
TI  - Overview of recent experimental studies on liver stem cells.
AB  - Since our review of the experimental evidence for liver epithelial stem cells in
      1997, a large body of new data has been added. The new studies have focused on
      the analysis of differentiation of candidate liver stem cells when they are
      transplanted into the liver in vivo and when cultured in vitro under defined
      conditions. The new studies that we review substantiate the existence of stem
      cells that can generate new lineages of hepatocytes and cholangiocytes,
      especially in severely damaged livers. However, the recent studies have
      introduced new areas of controversy about the essential nature of liver stem
      cells and about appropriate methods to analyze their properties and functions.
      Whether the major stem cell for hepatocytes and cholangiocytes is an endodermal
      epithelial cell that resides in the liver or a mesodermal cell from bone marrow
      is a current area of controversy. Another controversial topic concerns the
      appropriateness of cell culture to analyze liver epithelial cells. Both of these
      situations are addressed, if not yet conclusively solved, by the new data. From
      our review of recent data, we conclude that the major liver stem cell is an
      epithelial cell that is a liver resident, and that cell culture is a valuable,
      even necessary, adjunct for analyzing the properties of liver stem cells and for
      eventually identifying the molecular mechanisms that regulate their activation,
      proliferation, and differentiation.

PMID- 14722809
TI  - Isolation and characterization of mouse hepatic stem cells in vitro.
AB  - This article covers mouse cell lines showing the properties of hepatoblasts or
      oval cells and describes hepatocyte differentiation obtained from embryonic stem
      (ES) cells and mesenchymal adult progenitor cells. It considers the methods used
      for cultivation and differentiation of the cells, as well as the strengths and
      weaknesses of the different systems and perspectives for future research.
      Emphasis is given to hepatoblast cell lines because this is the material for
      which bipotentiality has been most clearly demonstrated and for which
      proliferation and differentiation conditions have been worked out.

PMID- 14722810
TI  - Characterization of the differentiation capacity of rat-derived hepatic stem
      cells.
AB  - The liver in an adult rat maintains a balance between cell gain and cell loss.
      Although normally proliferatively quiescent, hepatocyte loss such as that caused
      by partial hepatectomy (PH) invokes a rapid regenerative response to restore
      liver mass. This restoration of moderate cell loss and "wear and tear" renewal is
      largely achieved by hepatocyte self-replication. Furthermore, hepatocyte
      transplants in rats, in which a selective pressure for the transplanted cells can
      be applied, have shown that a certain proportion of hepatocytes can undergo
      significant clonal expansion, suggesting that hepatocytes themselves are the
      functional stem cells of the liver. Fetal liver may also harbor bipotential stem
      cells capable of sustained clonal expansion. More severe liver injury activates a
      potential stem cell compartment located within the canals of Hering, giving rise
      to cords of bipotential oval cells that can differentiate into hepatocytes and
      biliary epithelial cells. Other cell populations with hepatic potential reside in
      the bone marrow; whether these hematopoietic cells can function as stem cells for
      the rat liver remains to be confirmed. Pancreatic cells have also been found to
      have hepatocytic potential.

PMID- 14722811
TI  - Diversity of hepatic stem cells in the fetal and adult liver.
AB  - The liver is an organ with tremendous regenerative capacity. Hepatic stem cells,
      identified by flow cytometric sorting and single cell-based assays as c-Met
      (+)CD49f (+/low)c-Kit (-)CD45 (-)TER119 (-) cells in murine fetal livers, possess
      multilineage differentiation potential and self-renewing capability. These cells
      can differentiate in vitro as well as in vivo into some epithelia capable of
      reconstituting tissues within the liver, pancreas, and intestine following
      appropriate transplantation. The isolated fetal hepatic stem cells are also
      characterized by the ability to maintain their self-renewal capability in the
      developing liver. Thus, these cells may be ideal vehicles for delivering
      therapeutic genes to the liver. We also examined the relationship between fetal
      hepatic stem cells and hepatic oval cells in the adult liver. These two subtypes
      shared both multipotential capabilities of differentiation and surface marker
      expression profiles, suggesting that hepatic oval cells are probably the progeny
      of fetal hepatic stem cells. We also address the related topics of hepatocyte
      repopulation, exogenous hepatic stem cells, and transdifferentiation. Topics
      ranging from the fundamental properties and comprehensive descriptions of hepatic
      stem cells to current progress in the field are discussed in this brief article
      and our recent studies are addressed.

PMID- 14722812
TI  - Hepatic stem cells and liver repopulation.
AB  - Research on hepatic stem cells has entered a new era of controversy, excitement,
      and great expectations. Although adult liver stem cells have not yet been
      isolated, an enormous repopulating capacity of transplanted mature hepatocytes
      under conditions of continuous liver injury has been discovered. Stem/progenitor
      cells from fetal liver have been successfully isolated and transplanted,
      repopulating up to 10% of normal liver. However, progenitor cell lines from adult
      and embryonic liver have not shown significant repopulating activity. Intensive
      research on embryonic stem cells has revealed the first promising attempts to use
      these cells as a source of hepatic progenitors. Conditions for their
      differentiation in vitro, isolation of purified hepatic progenitor cells, and
      liver repopulation are currently being evaluated. Multilineage adult progenitor
      cells of mesenchymal origin from bone marrow, muscle, and brain may turn out to
      be the long-sought primitive potential stem cells remaining in adult tissues.

PMID- 14722813
TI  - The role of bone marrow stem cells in liver regeneration.
AB  - Hepatic oval cells involved in some forms of liver regeneration express many
      markers also found on hematopoietic stem cells (HSCs). In addition, multiple
      independent reports have demonstrated that bone marrow cells can give rise to
      several hepatic epithelial cell types, including oval cells, hepatocytes, and
      duct epithelium. These observations have resulted in the hypothesis that bone
      marrow resident stem cells, specifically HSCs, are an important source for liver
      epithelial cell replacement, particularly during chronic injury. The function of
      such stem cells in hepatic injury responses is the topic of this article. Taken
      together, the published data on the role of bone marrow stem cells in liver
      damage suggest that they do not play a significant physiological role in the
      replacement of epithelial cells in any known form of hepatic injury. Fully
      functional bone marrow-derived hepatocytes exist but are extremely rare and are
      generated by cell fusion, not stem cell differentiation. Nonetheless, bone marrow
      derived cells may play important indirect roles in liver regeneration. First,
      they may serve as a source for the replacement of endothelial cells. Second,
      hematopoietic cells, including lymphocytes, neutrophils, macrophages, and
      platelets, may provide crucial factors required for efficient healing of damaged
      liver.

PMID- 14722814
TI  - Human liver-derived stem cells.
AB  - The search for human oval cells or bi-potential stem cells in the human liver is
      the subject of intensive investigation. Fetal hepatocytes (hepatoblasts) have
      some proliferative and bipotential capacity, but access to sufficient numbers of
      cells remains limiting. Candidate stem cells in the adult normal and diseased
      human liver have been identified using markers such as OV6, CD34, c-kit and NCAM.
      Lack of stem cell marker specificity however, remains a problem and further, more
      specific markers are required. The molecular signaling molecules and
      transcription factors that control proliferation and cell differentiation
      pathways into hepatocyte or biliary phenotype are beginning to emerge. However,
      whether any of the current liver stem cell approaches will be converted into
      effective clinical cell transplantation or gene therapy treatments has yet to be
      proven.

PMID- 14722815
TI  - Progenitor cells in diseased human liver.
AB  - Hepatic progenitor cells are immature epithelial cells that reside in the
      smallest ramifications of the biliary tree in human liver. These cells are
      capable of differentiating toward the biliary and the hepatocytic lineages and
      represent the human counterpart of the oval cells in murine liver. An increased
      number of progenitor cells (referred to as "activation") and differentiation of
      the same toward hepatocytes or bile duct epithelial cells, or both, is a
      component of virtually all human liver diseases. The extent of progenitor cell
      activation and the direction of differentiation are correlated with the severity
      of the disease and the type of mature epithelial cell (hepatocyte or bile duct
      epithelial cell), respectively, that is damaged. Analogous to findings in animal
      models of hepatocarcinogenesis, human hepatic progenitor cells most likely can
      give rise to hepatocellular carcinoma. The factors that govern human hepatic
      progenitor cell activation and differentiation are beginning to be identified.

PMID- 14722819
TI  - Current issues in the diagnosis and management of dementia.
AB  - Aging, memory loss, Alzheimer's disease, and other forms of dementia assume
      increasing importance to patients, physicians, and society as our population
      becomes older. Mild cognitive impairment, topography and semiology of dementia
      syndromes, reversible forms of dementia, dementia therapy, driving, genetic
      testing of patients and family members, and caregiver risk are reviewed.

PMID- 14722820
TI  - Diagnosis and management of stroke (brain attack).
AB  - Clinicians commonly encounter patients with cerebrovascular disorders in the
      hospital. Now, as never before, there are many effective diagnostic and
      therapeutic modalities. Several examples of typical cases of stroke and transient
      ischemic attack are presented in order to illustrate a rational approach to
      diagnosis and treatment. A redefinition of transient ischemic attack and stroke,
      salient elements of the neurological history and examination, localization
      techniques, stroke mimickers, mechanisms of infarction and hemorrhage, acute
      stroke teams, thrombolysis, and secondary prevention are highlighted.

PMID- 14722821
TI  - Practical consultations: multiple sclerosis.
AB  - People with multiple sclerosis (MS) are increasingly referred for specialty care
      to tertiary centers, particularly for advice regarding initiation and monitoring
      of immunomodulatory therapies. However, the generalist must still be able to
      apply appropriate skills and technology to diagnose the disease and its
      complications, provide basic counseling of patients, and be aware of potential
      treatment options at the time of diagnosis and when therapeutic regimens fail. A
      general approach, supported by evidence where possible, to common and
      contemporary clinical issues in MS care is provided in a case-based narrative.

PMID- 14722822
TI  - Chronic daily headache: a rational approach to a challenging problem.
AB  - Chronic daily headache (CDH) is a significant public health problem with 3 to 5%
      of the population worldwide experiencing daily or near-daily headaches. Patients
      with CDH can be particularly challenging, and clinicians require a systematic
      approach to help guide investigations and management. The revised 2004
      International Headache Society Classification Criteria introduces formalized
      criteria for several CDH disorders including chronic migraine and medication
      overuse headache as well as new daily persistent headache, hemicrania continua,
      hypnic headache, and SUNCT syndrome. Medication overuse is common in patients
      with CDH who present to physicians. Familiarity and comfort with drug-withdrawal
      and detoxification strategies is therefore essential. Patients with chronic
      migraine and chronic cluster experience significant disability and diminished
      quality of life. The ability to manage these patients effectively is a rewarding
      clinical experience.

PMID- 14722823
TI  - Case studies in movement disorders.
AB  - Six cases representing the most commonly encountered movement disorders-restless
      legs syndrome with periodic limb movements, tics, myoclonus, chorea, essential
      tremor, and cervical dystonia-are presented. Discussion of each case focuses on a
      practical approach to recognizing the important clinical features of each
      movement disorder as well as the current therapeutic options. A detailed
      discussion of botulinum toxin follows the case on cervical dystonia, focusing on
      its mechanism of action, clinical indications, side effects, and dosing.

PMID- 14722824
TI  - Questions for the consultant: seizures and epilepsy.
AB  - Issues regarding management of acute and chronic seizures constitute one of the
      more frequent consultations that all neurologists encounter. With a significant
      medical and surgical therapeutic armamentarium now available, many clinicians are
      perplexed about how to approach the most basic of seizure consultation questions.
      In this article, four of the most commonly asked seizure consultation questions
      are reviewed: when antiepileptic drug (AED) treatment should be initiated; how to
      choose an AED; when to refer a patient for surgery; and when to withdraw AEDs in
      a seizure-free patient. By utilizing frequently encountered clinical scenarios,
      the decision-making process to best illustrate application of existing clinical
      evidence to the individual patient is explored.

PMID- 14722825
TI  - Using EEG in a consultative role.
AB  - The electroencephalogram (EEG) is a long-used tool assisting health care
      providers with the diagnosis, management, and treatment of various neurological
      disorders. This article highlights several scenarios in which a consultant may
      utilize the routine EEG in managing specific neurological cases. Eight case
      scenarios from a tertiary referral hospital are presented for the reader's
      consideration. Scenarios selected are new-onset seizures, encephalopathy,
      syncope, dementia, brain death, hypoxic-ischemic encephalopathy, status
      epilepticus, and migraine. A history in each condition is presented and is
      followed by a discussion of how useful an EEG may be in these specific
      situations. These eight cases highlight specific learning points where the EEG
      may be useful and how it can be practically incorporated into care of patients.
      Understanding how the EEG may be useful in the presented cases will allow the
      efficient and effective use of the EEG in similar clinical scenarios.

PMID- 14722826
TI  - Sleep disorders.
AB  - Patients with sleep disorders present with a variety of complaints including
      excessive daytime sleepiness, daytime spells, inability to sleep, uncomfortable
      sensation in the extremities, and unusual night time behaviors. This article
      provides eight vignettes on patients with sleep disorders including narcolepsy,
      idiopathic hypersomnia, obstructive sleep apnea, restless legs syndrome, and
      rapid eye movement behavior disorder. The discussion provides data regarding the
      epidemiology, pathophysiology, and diagnostic approach for these conditions. The
      various treatment options for these sleep disorders are also identified.

PMID- 14722827
TI  - Neurotologic issues.
AB  - Progress has been made in the diagnosis and treatment of inner ear disorders.
      Autoimmune inner ear disorders and Meniere's disease (MD), the prototype inner
      ear disease, are highlighted in this review of current knowledge and contemporary
      dietary, medical, surgical, and vestibular rehabilitation therapy. A number of
      other peripheral vestibular disorders are presented and contrasted with MD.

PMID- 14722828
TI  - Multifocal motor neuropathy with conduction block: current issues in diagnosis
      and treatment.
AB  - Multifocal motor neuropathy (MMN) with conduction block is an acquired,
      autoimmune-mediated neuropathy that is responsive to treatment. The clinical
      history is one of slowly, progressive distal weakness, which more commonly
      involves the upper extremities, and it affects mainly young adults. Physical
      examination reveals weakness without sensory loss in the distribution of
      individual nerves. Atrophy may be present, but hyperreflexia and spasticity are
      not seen. Electrophysiological studies reveal motor conduction blocks at sites
      not prone to compression with normal sensory responses. Immunoglobulin M anti-GM1
      titers may be elevated. Treatment with human immunoglobulin or cyclophosphamide
      has been shown to improve strength in the majority of patients with MMN in the
      short term. However, motor strength and function may gradually decline over years
      in spite of long-term therapy.

PMID- 14722829
TI  - What good is EMG to the patient and practitioner?
AB  - Electromyography (EMG) and nerve conduction studies (NCS) are not only tests to
      be performed in isolation and reported without consideration of the clinical
      context, but rather form part of what has been referred to as the
      electrodiagnostic consultation. Using all of the pertinent information available
      to the electromyographer performing the test, the electrodiagnostic consultation
      strives toward the goal of helping the patient and the referring physician to
      establish a correct diagnosis. Although not without limitations, EMG as an
      extension of the clinical history and physical examination can be a powerful and
      sensitive diagnostic tool. Like any tool, however, the final result depends on
      the skill and expertise with which it is wielded.

PMID- 14722832
TI  - [A german internet journal "Psycho-Social Medicine"!].

PMID- 14722833
TI  - [Changes of coping strategies in patients with therapy refractory epilepsy in the
      course of a ward based treatment with a holistic therapeutic approach].
AB  - In this study we examined whether individual coping strategies improve in the
      course of a ward based treatment with a holistic therapeutic approach. An
      increase in problem-focussed coping and a decrease in emotion-focussed coping or
      avoidance-oriented coping were considered as improvement. As a part of a
      comprehensive therapy monitoring 65 patients with therapy refractory epilepsy
      were studied with the Freiburg Questionnaire of coping with Illness (FKV) on the
      day after admittance to a specialized epilepsy ward. A second investigation with
      the FKV was performed on the day before discharge. A decrease in depressive
      coping and cognitive avoidance and an increase in problem focussed coping could
      be documented. These changes could not be interpreted as an effect of better
      seizure control or antidepressive drugs. This may be a hint for the efficacy of a
      holistic treatment approach to increase the patient's resources for a successful
      psychosocial adjustment to therapy refractory epilepsy.

PMID- 14722834
TI  - [The goals of nursing in inpatient psychosomatic medicine - an empirical
      approach].
AB  - Nursing plays an essential part in the acute psychosomatic inpatient treatment.
      The goals, which the nurses aim at while taking care of their patients, have,
      however seldom been investigated. This first systematic inquiry into the goals,
      which care at the clinic for psychosomatic medicine bears in mind, was carried
      out on a sample of 84 patients. These goals were evaluated and compared with
      different common outcome measures. Carers, first of all, aim at goals referring
      to the symptom, such as improving the patients' eating habits. Apart from that
      they mainly focus on goals not directly connected to the patients' physical
      condition, such as helping to improve the patients' self esteem. In some cases
      the nurses' estimate concerning the success of the treatment corresponds to that
      of the patients' to a greater extent than to that of the patients' personal
      therapist. Nursing in inpatient psychosomatic medicine extends much further than
      the demands of care normally imply. The knowledge concerning the patients' mental
      condition, which the nurses have according to this inquiry, ought to be used
      within the treatment.

PMID- 14722835
TI  - [Physical quality of life and social support in patients on the waiting list and
      after a lung transplantation].
AB  - BACKGROUND: The present study was carried out to assess quality of life, level of
      depression and perceived social support of patients on the waiting list and after
      a lung transplantation. METHODS: 19 patients on the waiting list for lung
      transplantation and 20 patients 5 - 47 months after transplantation were enrolled
      in the study. Quality of life was measured by the SF-36 Health Survey, the level
      of depression with Beck Depression Inventory (BDI) and the perceived social
      support with the questionnaire for social support (F-SOZU). RESULTS: Significant
      differences were observed in indicators regarding physical functioning, role
      physical, vitality, health perception and social functioning. Both groups showed
      equal levels of depression and their number of perceived support persons. The
      perceived support correlates negatively with the level of depression.
      Transplanted women reported significant more burdensome relationships when
      compared to transplanted men. CONCLUSION: The effects of lung transplantation are
      shown best in all indexes of SF-36 associated with physical functioning. In both
      groups social support is positively correlated with the quality of life and
      negatively correlated with the level of depression. Perceived positive
      relationships reduces the risk of psychological disturbance. However, the results
      may also point to a different coping pattern for patients with a low level of
      depression.

PMID- 14722836
TI  - [Questionnaire on parental attitudes and rearing practices (FEPS)].
AB  - A positive parent-child relationship is one of the most important determinants of
      a healthy cognitive, emotional and social development. The relationship from
      parent to child is determined by parenting styles. Parenting styles are
      characterised by the two dimensions parental attitudes and rearing practices. The
      development and the psychometric properties of a questionnaire on parental
      attitudes and rearing practices (FEPS), which contains an extended version of the
      Parental Bonding Instrument by Parker et al. (PBI, 1979) and two scales on
      parental reinforcement and punishment behaviour, is presented. In a sample of 457
      women and 159 men factorial and item analysis revealed four scales (care,
      autonomy, low punishment and low material reinforcement). The care dimension
      contained items of immaterial reinforcement on the positive pole and items of
      coldness and ignorance as means of punishment on the negative pole. Based on
      findings from its first application in a clinical study it can be assumed that
      the FEPS differentiates between clinical and non-clinical populations.
      Additionally, varying patterns of the four scales may emerge as risk factors for
      the development of certain psychiatric/psychological problems.

PMID- 14722837
TI  - [Cost effectiveness of integrated internal medicine].
AB  - The medical diagnoses and their economic level of severity as well as the
      treatment costs and the proceeds of an integrated internal - psychosomatic ward C
      were compared with two conventional internal wards A and B of a general medical
      department within a hospital of tertiary care level. With a similar economic
      level of severity of the diagnoses, lethality and costs for nursing care given
      the medical treatment costs of C were significant lower and the proceeds (minus
      medical treatment costs and nurses' salaries) calculated according to G-DRG
      version 1.0 higher than those of A and B. Integrated internal medicine is more
      cost effective compared to conventional internal medicine.

PMID- 14722839
TI  - Role of thrombolysis in free-flap salvage.
AB  - Approximately 5 percent of microvascular free-tissue transfers fail; often this
      is due to microvascular or peri-anastomotic thrombosis. Various reports have
      advocated the use of thrombolytics for salvage of these flaps, although clinical
      evidence supporting this approach is sparse. The authors attempted to review
      their own and other published results and present an algorithm for the use of
      thrombolytics in the management of failing free flaps. A retrospective review of
      590 free flaps, revealed 71 (12 percent) requiring re-exploration for impending
      flap failure, determined by standard clinical indicators. Forty-four (62 percent)
      were found to have pedicle thrombosis and 20 (28 percent) received thrombolysis
      with streptokinase or urokinase. All 44 flaps were grouped by final outcome and
      thrombolytic use for comparison. In 24 (55 percent) of the flaps with evidence of
      thrombosis, the use of thrombolytics was felt to be inappropriate or unnecessary;
      13 (54 percent) of these were salvaged. Twenty flaps, however, did receive
      thrombolysis and 6 (30 percent) of these were salvaged. There was no
      statistically significant difference among groups with respect to preoperative
      risk factors, age, gender, flap type, and site of anastomotic thrombosis. There
      was a twofold higher use of vein grafts in the failed vs. salvaged flaps (36
      percent vs. 15.7 percent), and no flaps with vessel grafts were salvaged with
      thrombolytics. Despite the fact that all flaps were re-explored within 3 hr of a
      problem being detected, the mean time from the initial operation to re
      exploration was significantly higher in flaps that did not respond to
      thrombolytics (63. 8 vs. 32.8 hr, respectively, p=0.0457). Also, the mean time to
      re-exploration was significantly higher in the salvaged flaps receiving
      thrombolysis vs. those that did not (32.8 vs. 22.3 hr, respectively, p=0.0264).
      While early detection and re-exploration are crucial for salvaging failing free
      flaps, those flaps unresponsive to other standard interventions may benefit from
      the selective use of thrombolytics.

PMID- 14722840
TI  - Multiple vascular anastomoses with vein grafts for salvage of congestive flaps.
AB  - The authors present two cases in which the venous drainage of transferred flaps
      was compromised and the flaps were salvaged by vein grafts. Traditionally, once
      transferred free flaps had become congestive, surgeons would re-anastomose the
      thrombosed veins, and administer anticoagulants or carry out peripheral vessel
      dilation. These authors recommend not only re-anastomosis of veins, but also
      additional venous drainage, with or without vein grafts.

PMID- 14722841
TI  - Refinement of minimally invasive harvest of gracilis muscle flap without
      endoscopic assistance.
AB  - Minimally invasive surgery without endoscopic assistance for gracilis muscle flap
      harvest is extensively used at the authors' institution. However, the proximal
      incision is still visible. The purpose of this study was to place the proximal
      incision in the groin area, to improve the cosmetic result at the donor site. In
      the reported series, nine male and three female patients were evaluated, with
      patient ages ranging from 31 to 75 years. Ten patients had lower extremity
      reconstruction, one had a forearm defect, and the other, a head and neck defect.
      The proximal incision was 5 to 6 cm in length in the groin area. The distal
      incision was 1.5 cm in length around the knee. After adequate exploration and
      dissection of the major pedicle of the gracilis muscle flap, which was located at
      7 to 8 cm below the groin crease under direct vision, a standard long blunt
      dissector was used to separate the gracilis muscle. The average incision was
      about 7 cm in length, and the harvesting time was 55 min. All the free muscle
      transfers were successful and without major complications. The proximal incision
      was almost invisible after 3 months. Two patients developed partial loss of the
      skin graft, requiring further skin grafting. Compared with the conventional
      technique, this method proved to be advantageous in its easier performance,
      shorter incision, fewer morbidities, and better appearance at the donor site.

PMID- 14722842
TI  - Microsurgical management of the diabetic foot.
AB  - Allthough there has been dramatic progress in limb salvage in recent decades,
      management of nonhealing wounds in diabetic patients continues to present a
      dilemma for the reconstructive surgeon. However, the acceptance of free-flap
      resurfacing of diabetic foot ulcers has increased in recent years. This study
      reviews 10 microvascular free muscle flaps in nine patients over a mean follow-up
      period of 44 months. Five patients had evidence of peripheral vascular disease.
      There was one flap loss, and nine flaps were transferred successfully. No
      perioperative mortality was encountered. The operations required a long, costly
      hospitalization (average hospital stay was 40 days). Seven of eight patients
      whose flaps survived had complications related to the free-flap recipient site.
      These seven patients underwent 20 secondary surgical procedures due to arterial
      and venous thrombosis, partial necrosis of the skin grafts, minor local
      infections, and gangrene or necrosis of the remaining toes. In three patients,
      progressive ischemic necrosis of the remaining toes, with total survival of the
      flap, was attributed to a microvascular steal phenomenon. However, all eight
      patients whose flaps survived subsequently ambulated on their flaps. The study
      demonstrates that microvascular surgery may result in functional lower-extremity
      salvage in diabetic patients with foot wounds that are not treatable by local
      flaps or skin grafts, and are destined for amputation.

PMID- 14722843
TI  - Dorsal hand coverage with free serratus fascia flap.
AB  - In reconstructing a defect on the dorsum of the hand, with the extensor tendons
      exposed or even missing, functional, as well as cosmetic, goals are of major
      importance. The authors present three cases of extensor tendon reconstruction,
      combined with soft-tissue reconstruction, with the free serratus fascia flap, the
      connective tissue over the serratus muscle, for dorsal hand coverage. The flap
      consists of thin and well-vascularized pliable tissue, with gliding properties
      excellent for covering exposed tendons. It is based on the branches of the
      thoracodorsal artery, which are raised in the flap, leaving the long thoracic
      nerve intact on the serratus muscle. Coverage of the flap with split-thickness
      skin graft is done immediately. The free serratus fascia flap is an ideal flap
      for dorsal hand coverage when the extensor tendons are exposed, especially
      because of low donor-site morbidity.

PMID- 14722844
TI  - Secure flap fixation to bony tissue using an anchoring system in skull-base
      surgery.
AB  - The reconstruction of extensive skull-base defects using flap transfer decreases
      crucial postoperative complications. However, flap fixation to bony tissue is
      often difficult, especially if there is no soft tissue to pass sutures through,
      and unsteady flap fixation causes dead space formation or displacement of the
      transferred flap due to gravity. The authors used an anchoring system for secure
      flap fixation in seven cases with difficult flap fixation, using the conventional
      suturing technique. Anchors were inserted at strategic points in the bony tissue,
      and secure flap fixation was achieved in all cases. Postoperative CT scans showed
      no dead space formation, and major postoperative complications were not observed.
      The anchoring system can be buried in bony tissue with a thickness of more than 4
      mm, and it enables reliable flap fixation and dead space obliteration. Although
      the cost is relatively high, the procedure is simple and lowers the risk of
      crucial postoperative complications in skull-base surgery.

PMID- 14722845
TI  - The "Sun window" - a simple and effective alternative to the use of background
      contrast material during microvascular anastomosis.
AB  - A new and simple alternative method, the "Sun window," is introduced for creating
      a comfortable environment while doing microvascular anastomoses. A prospective
      randomized study, analyzing the anastomosis time for 34 free radial forearm
      flaps, was conducted to validate the effectiveness of this method. The time
      required for doing anastomoses with and without a "Sun window" are 8.74 +/- 1.46
      and 10.36 +/- 1.20, respectively, p < 0.01. The results demonstrated that the
      "Sun window" is an effective method for promoting the patency rate and accuracy
      of microvascular anastomosis.

PMID- 14722846
TI  - Preserving osseous viability in osteocutaneous flap prefabrication: experimental
      study in rabbits.
AB  - This study presents a technique that preserves osseous viability in prefabricated
      osteocutaneous flaps with a soft-tissue vascular carrier, with a pedicled skin
      flap acting as the vascular carrier to neovascularize a partially devascularized
      bone segment before its transfer. Using a total of 50 New Zealand White rabbits,
      two groups were randomized as experimental and control animals. In the
      experimental group (n = 30), a bipedicled dorsal scapular skin flap was anchored
      with sutures to the scapular bone, by bringing it into contact with the exposed
      dorsal surface of the bone after stripping the dorsal muscular attachments.
      Following 4 weeks of neovascularization, the prefabricated composite flaps were
      harvested, based on the caudally-based dorsal skin flap, after stripping the
      ventral muscular attachments of the bone. In the control group (n = 20), non
      vascularized scapular bone grafts were implanted under bipedicled dorsal scapular
      skin flaps with sutures. After 4 weeks, prefabricated composite flaps were
      harvested, based on the caudally-based dorsal skin flap. In both groups, on day 7
      after the second stage, the viability of the bony component of the flaps was
      evaluated by direct observation, scintigraphy, measurement of bone metabolic
      activity, microangiography, dye injection study, and histology. Results indicated
      that the bone segments in the experimental group demonstrated a greater survival
      than in the control group. The authors conclude that this technique of
      osteocutaneous flap prefabrication preserves the viability of the bony component
      with a soft-tissue vascular carrier, in contrast to the conventional method of
      pre-transfer grafting. The technique may be useful clinically in selected cases.

PMID- 14722849
TI  - Colon polyps and cancer.
AB  - Screening for colorectal neoplasia still is the best method of reducing the
      mortality due to colorectal cancer, and it is to be hoped that fecal occult blood
      test programs will expand in the near future and be combined with appropriate
      endoscopy. There are substantial problems with compliance in large programs with
      occult blood tests as well as endoscopy. Colonography and DNA testing in feces
      are not yet suitable for population screening. Diagnostic strategies in
      symptomatic patients are becoming more selective, in the hope of avoiding many
      superfluous examinations without increasing the risk of missing cancers. New
      results have confirmed the preventive effect of long-term aspirin use on adenoma
      recurrence, but the most cost-effective dosage is not clear; the mechanism of
      action is also uncertain, but seems to involve cyclooxygenase-2. The risk of
      adenomas does not appear to be associated with low consumption of folate, but
      with low intake of fiber. A number of biomarkers have been evaluated in polyp
      patients, but so far surveillance is still based on endoscopic experience, which
      is less than optimal. Attempts have been made to restrict the number of
      surveillance endoscopies and reduce the pathologist's workload. The place of
      argon plasma coagulation has been clearly defined in connection with piecemeal
      removal of large sessile adenomas. Advances have been achieved in surgery and
      radiotherapy for rectal cancer, and acute surgery for colonic cancer with severe
      obstruction will be less common after the introduction of the metal stent.

PMID- 14722850
TI  - Therapeutic pancreatic endoscopy.
AB  - In view of increasingly accurate noninvasive diagnostic imaging modalities for
      pancreatic diseases, endoscopic retrograde cholangiopancreatography (ERCP) should
      be mainly restricted to therapeutic indications. Acute pancreatitis is still the
      most common complication of ERCP. Prevention measures should focus in particular
      on well-defined risk groups. Temporary pancreatic duct drainage, preferably using
      small-diameter endoprostheses, can reduce the incidence of post-ERCP pancreatitis
      in at-risk individuals. By contrast, pharmacological prevention does not appear
      to be effective. ERCP in conjunction with sphincter of Oddi manometry frequently
      reveals the diagnosis of undetermined causes of acute recurrent pancreatitis.
      Endoscopic sphincterotomy (EST) is the treatment of choice in patients with
      sphincter of Oddi dysfunction or papillary stenosis. For these indications, dual
      pancreaticobiliary sphincterotomy promises a lower early morbidity and a better
      long-term outcome than biliary EST alone. In patients with pancreatic divisum,
      the cannulation rate of the dorsal duct can be improved by methylene blue
      staining and/or stimulation of the pancreatic secretion. Papillotomy of the minor
      papilla with short-term stenting appears to be an effective and safe approach for
      associated acute recurrent pancreatitis. Large-scale trials indicate that the
      majority of symptomatic patients with chronic pancreatitis can be well managed in
      the long term by endoscopic interventions. There is still a lack of prospective
      randomized controlled trials on endotherapy for chronic pancreatitis; however,
      they are also lacking for the surgical approach. Endoscopic and/or
      endosonographically guided drainage has become the treatment of choice for the
      majority of symptomatic pancreatic pseudocysts. Transmural debridement of
      pancreatic abscesses and infected necroses is still investigational, but appears
      to offer a minimally invasive alternative to surgery in selected cases.
      Pancreatic endotherapy is technically demanding and potentially hazardous; these
      interventions should be restricted to high-volume centers with options for an
      interdisciplinary team approach. Methods that have not yet been established
      should be evaluated in carefully designed prospective trials.

PMID- 14722851
TI  - Endoscopic ultrasonography.
AB  - Increasing research related to endoscopic ultrasonography is published every
      year. A welcome trend towards outcomes-oriented research, evaluating the impact
      of endoscopic ultrasonography on patient management, is continuing. As experience
      regarding the safety and efficacy of endosonography-guided fine-needle aspiration
      in different clinical settings accumulates, this procedure is rapidly becoming a
      key component of endoscopic ultrasonography. Although promising developments in
      the fields of guided tissue sampling and image acquisition and analysis are being
      reported, innovative technical ideas need to be incorporated into the existing
      endoscopic ultrasound technology to take it to the next level of applications,
      such as endosurgery.

PMID- 14722852
TI  - Preparation, premedication, and surveillance.
AB  - The main criteria for assessing conscious sedation (perhaps now more correctly
      termed "moderate sedation/analgesia") continue to be patient satisfaction and
      comfort, short duration, amnesia, and above all, patient safety. The problems
      reviewed last year - including the increasing pressure on endoscopy units to
      perform yet more procedures, reduce costs, and achieve shorter patient turn
      around times - certainly have not gone away. Studies reviewed this year suggest
      that although many endoscopic procedures, such as oesophagogastroduodenoscopy
      (OGD), colonoscopy, and endoscopic ultrasonography (EUS) can indeed be performed
      without intravenous sedation, many patients still prefer to be sedated. Further
      papers on the possible role of ultrathin endoscopes in unsedated OGD are reviewed
      here. A study in Italy comparing virtual computed-tomographic (CT) colonography
      and conventional colonoscopy suggests that unsedated colonoscopy is unlikely to
      meet with wide acceptance. Audits of colonoscopy in both the United States and
      the United Kingdom suggest that there is still a long way to go before caecal
      intubation rates of more than 90 % are regularly attained. The evidence suggests
      that some endoscopists are using larger doses of a midazolam and pethidine
      combination than are generally recommended (particularly in elderly patients),
      and sedation-related deaths are still occurring. Impressively large clinical
      studies, particularly those from Switzerland, on the use of propofol administered
      by nonanaesthetists are leading to reconsideration of the earlier view that
      propofol should only be used by anaesthetists. If propofol is to be used more
      widely and become an agent administered by endoscopists (or nursing staff), then
      considerable improvements in the standard of airways management will be needed.
      Several new studies relating to bowel-cleansing agents and the use of a
      carbohydrate/electrolyte "cholera mixture" to prevent the associated
      intravascular volume contraction have been published. Warm water is a cheap and
      effective way of reducing colonic spasm during colonoscopy, and intraluminal
      peppermint oil is a good antispasmodic in the stomach as well as the colon.
      Sedation should still be regarded as one part of an overall "endoscopy package".
      Finally, more attention needs to be given to patients' complaints regarding what
      are often considered by endoscopists to be "trivial complications" if the
      patients are to have a positive experience of their examination that will lead to
      them being prepared to come back a second time.

PMID- 14722853
TI  - Small-bowel endoscopy.
AB  - The role of small-bowel endoscopy in the management of small-bowel diseases is
      still evolving. During the last year, capsule endoscopy has developed from being
      an emerging method in gastroenterology to become a clinical reality, and it must
      now be considered critically. A number of peer-reviewed studies have been
      published that compare the method with push enteroscopy in patients with obscure
      gastrointestinal bleeding. In other studies, capsule endoscopy has been compared
      with traditional radiographic methods of examining the small bowel. The potential
      of capsule endoscopy for diagnosing small-bowel diseases has also been evaluated,
      particularly in patients with suspected Crohn's disease. Although this innovative
      diagnostic method has now entered clinical practice, it must be stressed that
      both push enteroscopy and intraoperative enteroscopy still have a precise and
      valid role in the management of patients with small-bowel diseases, as may be
      seen from several of the studies that are reviewed here. Capsule endoscopy will
      probably become a first-line tool for detecting abnormalities of the small bowel,
      and very probably this will entail redefining some diagnostic algorithms for
      diseases involving the small bowel. Nevertheless, further studies are required
      before today's clinical practice can be definitively modified, and these should
      make particular reference to the outcome in patients who undergo capsule
      endoscopy.

PMID- 14722854
TI  - Ulcers and gastritis.
AB  - Significant advances continue to be made in the area of gastritis and ulcer
      disease. Studies to identify the most appropriate use of capsule endoscopy have
      now confirmed that it is superior to other methods for identifying small-bowel
      mucosal pathology and sites of obscure gastrointestinal bleeding. It has
      increasingly been recognized that the complications of ulcer disease are
      secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to
      interactions between NSAIDs and Helicobacter pylori. Effective prophylaxis for
      NSAID ulcers in H. pylori-negative individuals continues to be a challenge, as it
      has become clear that conclusions from studies focusing on "endoscopic ulcers" in
      patients whose H. pylori status was unknown provided a false sense of security.
      The concept of multifocal atrophic gastritis has been challenged. The precursor
      lesion to gastric cancer now appears to be a sheet of pseudopyloric metaplasia
      advancing into the gastric body with islands of intestinal metaplasia embedded
      within it. Multifactorial models such as those proposed for understanding
      periodontal disease, including the organism, environmental factors, and host
      factors, appear particularly applicable to understanding the pathogenesis of H.
      pylori-associated gastric cancer.

PMID- 14722855
TI  - Minimally invasive surgery.
AB  - Minimally invasive surgery is replacing the traditional open surgical approach
      for many abdominal procedures. The benefits of reduced pain, quicker return of
      oral intake, shorter hospitalizations, and improved cosmetic results all support
      the increasing use of the laparoscopic approach. This review identifies important
      articles published in the literature on minimally invasive surgery from June 2002
      to August 2003, with the objective of identifying future trends and directions in
      laparoscopic surgery. The topics of articles reviewed in detail include minimally
      invasive techniques applied to esophageal tumors, morbid obesity, malignant liver
      tumors, gallbladder disease, pancreatic pathology, colon cancer, and robotic
      prostatectomy.

PMID- 14722856
TI  - Nonvariceal upper gastrointestinal bleeding.
AB  - Although the incidence of nonvariceal upper gastrointestinal bleeding (NVUGIB)
      may be decreasing, the case fatality associated with it remains unchanged. What
      do the most recent studies tell us about medical and endoscopic therapy?
      Erythromycin is a potentially useful adjunct to endoscopy, and further data are
      needed to establish its role in the management of patients with NVUGIB. The use
      of proton-pump inhibitors in addition to combination endoscopic therapy appears
      to reduce the rebleeding rate consistently across different studies; the route of
      administration, dosage, and duration of treatment require further definition.
      Although two controlled studies suggest improved outcomes with clot removal and
      endoscopic therapy, the exact role of endoscopic treatment in the setting of
      overlying clots remains controversial. Hemoclips have not been found, in general,
      to be superior to the available endoscopic techniques. Currently, other
      hemostatic techniques such as injection and thermocoagulation - and in
      particular, combination therapy using both methods - are preferable. No major
      "breakthrough" endoscopic treatment has emerged. Newer endoscopic therapies such
      as cryotherapy are interesting, but have not had widespread application.
      Endoscopic suturing techniques, as used in the treatment of esophageal reflux and
      obesity, have not been adapted to the management of gastrointestinal bleeding.

PMID- 14722857
TI  - United European gastroenterology week 2003: perspectives in gastrointestinal
      endoscopy.

PMID- 14722858
TI  - Endoscopic treatment outcomes in watermelon stomach patients with and without
      portal hypertension.
AB  - BACKGROUND AND STUDY AIMS: Watermelon stomach is a source of recurrent
      gastrointestinal hemorrhage and anemia. The aims of this study were to describe
      the endoscopic appearance and treatment outcomes in watermelon stomach patients
      with and without portal hypertension. PATIENTS AND METHODS: All patients with
      watermelon stomach enrolled in a hemostasis research group's prospective studies
      from 1991 to 1999 were identified. Investigators collected data using
      standardized forms. Comparisons were made using the chi-squared test, Wilcoxon
      rank-sum test, and Wilcoxon signed-rank test. RESULTS: Twenty-six of 744 (4 %)
      consecutively enrolled patients with nonvariceal upper gastrointestinal
      hemorrhage had watermelon stomach as the cause. Eight of these 26 patients (31 %)
      also had portal hypertension. These patients had diffuse antral angiomas, as
      opposed to the classic linear arrays seen in those without portal hypertension.
      The demographic data and clinical presentations of the two groups were otherwise
      similar. Palliative endoscopic treatment was associated with a significant rise
      in hematocrit and a decrease in the need for blood transfusion or hospitalization
      in watermelon stomach patients with and without portal hypertension. CONCLUSIONS:
      Watermelon stomach patients with and without portal hypertension had similar
      clinical presentations. The endoscopic findings differed in that those with
      portal hypertension had more diffuse gastric angiomas. Bleeding was effectively
      palliated by endoscopic treatment, regardless of the presence of portal
      hypertension.

PMID- 14722859
TI  - Comparison of duodenal stent placement with surgical gastrojejunostomy for
      palliation in patients with duodenal obstructions caused by pancreaticobiliary
      malignancies.
AB  - BACKGROUND AND STUDY AIMS: Palliative treatment for duodenal stenosis with an
      enteral stent is effective in enhancing the quality of life of patients with
      duodenal obstruction. There have been no thorough comparisons of duodenal stent
      placement with standard surgical gastrojejunostomy. The present study evaluated
      the outcome of duodenal stent placement and surgical gastrojejunostomy for
      palliation of duodenal stenosis caused by pancreaticobiliary malignancies.
      PATIENTS AND METHODS: Medical records for patients who underwent palliative
      enteral stenting during the past 9 years were retrospectively reviewed, and the
      patients' clinical outcome was compared with that in patients who underwent open
      surgical gastrojejunostomy during the same period. Patients who underwent
      prophylactic gastrojejunostomy were excluded from the study. RESULTS: Twenty
      patients (11 men, nine women; mean age 71.8 years) with pancreaticobiliary
      malignancy underwent palliative enteral stenting (stent group). Nineteen patients
      (12 men, seven women; mean age 68.7 years) with pancreaticobiliary malignancies
      underwent surgical gastrojejunostomy (bypass group). In the stent group, the
      diagnoses were 12 pancreatic cancers, six gallbladder cancers, one bile duct
      cancer, and one ampullary cancer. In the bypass group, the diagnoses were 14
      pancreatic cancers and five gallbladder cancers. There were no significant
      differences between the two groups with regard to clinical background. Both
      procedures were successful. There were no differences between the two groups with
      regard to the technical or clinical success rates, patient survival, possibility
      of discharge, need for parenteral nutrition, or incidence of complications.
      However, the time from the procedure to resumption of food intake was shorter in
      the stent group than in the bypass group (1 day vs. 9 days; P < 0.0001).
      Improvement in the performance score after the procedure was observed more
      frequently in the stent group (65 % vs. 26.3 %; P < 0.05). In terms of the median
      hospital stay from the time of the procedure to the time of initial discharge
      home (12 patients vs. nine patients), there was no statistical difference (15
      days vs. 30 days) due to the small size of the sample. There was no procedure
      related mortality in either group. CONCLUSIONS: Palliative stent placement was
      more beneficial than surgical gastrojejunostomy in enhancing the quality of life
      of patients with duodenal obstruction due to pancreaticobiliary malignancies.

PMID- 14722860
TI  - Endoscopic band ligation for control of acute peptic ulcer bleeding.
AB  - BACKGROUND AND STUDY AIMS: The use of endoscopic band ligation (EBL) is being
      extended to treat various causes of upper and lower gastrointestinal bleeding.
      The aim of this study was to evaluate the usefulness of EBL for control of acute
      peptic ulcer bleeding and to define the lesions that are most suitable for this
      technique. PATIENTS AND METHODS: 19 patients with major stigmata of acute peptic
      ulcer bleeding were treated using EBL; 11 patients had active bleeding and eight
      patients had a nonbleeding visible vessel. RESULTS: The site of acute peptic
      ulcer bleeding was the stomach in 12 patients, the duodenum in four patients, and
      Billroth II anastomosis in three. Initial hemostasis was achieved in 19 patients
      (100 %) in a single session. There were no rebleeding episodes in any of the
      patients, and there was no bleeding-related or procedure-related death. During
      long-term outpatient follow-up, bleeding did not recur. CONCLUSIONS: EBL is an
      effective and safe endoscopic treatment for small-sized nonfibrotic acute peptic
      ulcer bleeding. Larger studies in patients with acute peptic ulcer bleeding are
      needed to confirm these promising results.

PMID- 14722861
TI  - Photodynamic therapy for malignant biliary obstruction: a case series.
AB  - We describe four elderly patients (age range 73-85 years) with bile duct
      carcinoma who were treated with photodynamic therapy. These patients could not be
      treated surgically because of the presence of cardiopulmonary disease and the
      extent of the bile duct carcinoma. Prior to photodynamic treatment the patients
      underwent percutaneous transhepatic biliary drainage (PTBD) to relieve jaundice.
      The photodynamic therapy was carried out under percutaneous transhepatic
      cholangioscopy, 2 days after intravenous administration of sodium porfimer (2
      mg/kg). Excimer dye laser was used to irradiate the obstructive lesion with an
      energy dosage of 50 J/cm2 (total irradiation dose 150-250 J/cm2) and stenotic
      site with a dosage of 50-100 J/cm2. Photodynamic therapy was achieved safely
      without occurrence of cholangitis in all patients, and was followed by metallic
      stent placement, resulting in the improvement of performance levels in three
      patients who did not have liver metastases. Photodynamic therapy via the PTBD
      route is a safe and promising palliative therapy for selected elderly patients
      with bile duct carcinoma.

PMID- 14722862
TI  - Capsule endoscopy in chronic gastrointestinal bleeding.

PMID- 14722863
TI  - Controlled trial of wireless capsule endoscopy versus push enteroscopy: control
      not yet perfect.

PMID- 14722865
TI  - A useful new endoscopic marking technique for endoscopic mucosal resection of
      early gastric cancer.

PMID- 14722866
TI  - Detection of a foreign body during laparoscopy for differential diagnosis in a
      patient with ascites.

PMID- 14722867
TI  - An inexpensive training method for percutaneous endoscopic gastrostomy.

PMID- 14722868
TI  - Endoscopic treatment of esophageal carcinosarcoma: report of a case.

PMID- 14722869
TI  - Complete spontaneous submucosal dissection of the sigmoid colon.

PMID- 14722879
TI  - Infected erythrocyte binding to hyaluronic acid and malaria in pregnant women.

PMID- 14722880
TI  - Plasmodium falciparum-infected erythrocytes demonstrate dual specificity for
      adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive
      properties.
AB  - Hyaluronic acid (HA) and chondroitin sulfate A (CSA) have been identified as
      receptors for adhesion of Plasmodium falciparum-infected erythrocytes (IEs) and
      appear to be involved in mediating parasite accumulation in the placenta. We
      demonstrate here that some, but not all, parasite populations can adhere to both
      receptors, and we identify distinguishing features of adhesion. Adhesion to HA
      and CSA was greatest among pigmented trophozoite-infected erythrocytes and at
      physiologic pH and was associated with a lack of rosette formation and little
      adhesion to CD36 and intercellular adhesion molecule-1. Adhesion to HA was
      sensitive to trypsin cleavage of the IE surface, whereas trypsin-resistant and
      trypsin-sensitive CSA adhesion were both observed. Soluble HA, but not CSA, could
      cause aggregation or clumping of IEs. Different HA types varied in adhesion
      inhibitory activity, which was altered by physical treatment, suggesting that
      structural features of HA influence IE interactions. These findings have
      important implications for understanding the pathogenesis of malaria,
      particularly in pregnancy.

PMID- 14722881
TI  - Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to
      activated endothelial cells.
AB  - Severe malaria is characterized by the sequestration of Plasmodium falciparum
      infected erythrocytes (IEs). Because platelets can affect tumor necrosis factor
      (TNF)-activated endothelial cells (ECs), we investigated their role in the
      sequestration of IEs, using IEs that were selected because they can adhere to
      endothelial CD36 (IE(CD36)), a P. falciparum receptor that is expressed on
      platelets. The results of coincubation studies indicated that platelets can
      induce IE(CD36) binding to CD36-deficient brain microvascular ECs. This induced
      cytoadhesion resisted physiological shear stress, was increased by EC stimulation
      with TNF, and was abolished by anti-CD36 monoclonal antibody. Immunofluorescence
      and scanning electron microscopy results showed that platelets serve as a bridge
      between IEs and the surface of ECs and may therefore provide receptors for
      adhesion to microvascular beds that otherwise lack adhesion receptors. 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- 14722882
TI  - The deformability of red blood cells parasitized by Plasmodium falciparum and P.
      vivax.
AB  - Red blood cells (RBCs) must deform considerably during their multiple passages
      through the microvasculature and the sinusoids of the spleen. RBCs infected with
      Plasmodium falciparum (Pf-IRBCs) become increasingly rigid as they mature but
      avoid splenic clearance by sequestering in venules and capillaries. In contrast,
      RBCs infected with P. vivax (Pv-IRBCs) do not sequester. We compared the effects
      of P. vivax and P. falciparum infection on RBC deformability in a laminar shear
      flow system. Pf-IRBCs became more rigid as the parasite matured, but equivalent
      maturation of Pv-IRBCs resulted in a doubling of flexibility. Coincidentally, the
      IRBC surface area increased from 56.7+/-1.3 microm2 to 74.7+/-0.6 microm2 to
      90.9+/-1.1 microm2 in ring-, trophozoite-, and schizont-stage Pv-IRBCs,
      respectively, whereas Pf-IRBCs did not increase in size. P. vivax increases the
      deformability of IRBCs and thereby avoids splenic entrapment.

PMID- 14722883
TI  - Plasmodium falciparum clonal population dynamics during malaria treatment.
AB  - We have developed a new fragment-analysis method to enumerate the clones and to
      quantify their proportions within Plasmodium falciparum isolates. We
      prospectively enrolled 20 adult patients with uncomplicated malaria who were
      returning to France from various sub-Saharan countries, from January 2000 through
      July 2001. The analysis of clonal populations was performed on blood samples
      obtained at 10 times: 1 before treatment with oral quinine and 9 during the first
      96 h of the treatment. The resistance genotypes pfcrt and dhfr were determined
      for chloroquine and antifolinics. Multiple P. falciparum genotypes were detected
      in 19 (95%) of 20 patients: 2, 3, 4, and 5 genotypes were found in 4, 9, 4 and 2
      patients, respectively. Disappearance and reappearance of some clones within a
      few hours was observed. Individual clones represented 0.4%-99.4% of total
      parasitemia. Surprisingly, in 10 of 15 subjects tested, resistance genotypes
      varied according to the time of blood collection. These findings may have
      important implications with regard to the interpretations of resistance studies.

PMID- 14722884
TI  - CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by
      rodent macrophages.
AB  - Phagocytic cells represent an important line of innate defense against malaria;
      however, little is known of the mechanism by which macrophages recognize
      Plasmodium falciparum-parasitized erythrocytes (PEs). Using macrophages from CD36
      wild-type (WT), CD36-null, and CD36 transgenically-rescued rodents, we
      demonstrate a major role for CD36 in the phagocytosis of PEs. WT macrophages
      display enhanced phagocytic capacity for nonopsonized PEs, compared with that for
      CD36-null mouse and rat macrophages. Transgenic rescue of CD36-deficient rats
      restored macrophage phagocytic capacity for PEs. CD36 receptor blockade with
      monoclonal antibodies and proteolytic cleavage of CD36 ligands from the surface
      of PEs inhibited the uptake of PEs. Up-regulation of rodent CD36 by use of
      peroxisome proliferator-activated receptor (PPARgamma) agonists increased the
      phagocytosis of PEs. CD36-mediated uptake of PEs did not result in increased
      tumor necrosis factor-alpha secretion, of which high levels are associated with
      adverse outcomes in malaria. These studies support the use of these rodent models
      to examine PE-CD36 interactions.

PMID- 14722885
TI  - Chemokine receptor expression on the surface of peripheral blood mononuclear
      cells in Chagas disease.
AB  - We evaluated the expression of chemokine receptors (CCR1, CCR2, CCR5, and CXCR4)
      on the surface of peripheral blood mononuclear cells obtained from patients with
      chronic chagasic cardiomyopathy (CCC) and noninfected individuals. Only CCR5 and
      CXCR4 expression was different on the surface of the subsets (CD4, CD8, and CD14)
      evaluated. Patients with mild CCC had elevated leukocyte expression of CCR5,
      compared with noninfected individuals or those with severe disease. CXCR4
      expression was lower on leukocytes from patients with severe CCC. The
      differential expression of both receptors on leukocytes of patients with CCC was
      consistent and clearly correlated with the degree of heart function such that the
      lower the heart function, the lower the expression of either CCR5 or CXCR4. These
      results highlight the possible participation of the chemokine system in early
      forms of chagasic cardiomyopathy and the relevance of heart failure-induced
      remodeling in modifying immune parameters in infected individuals.

PMID- 14722886
TI  - Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles.
AB  - A prospective study of clinical and cytokine profiles of 107 infants with dengue
      hemorrhagic fever (DHF)/dengue shock syndrome (DSS) was conducted. Fever,
      petechiae on the skin, and hepatomegaly were the most common clinical findings
      associated with DHF/DSS in infants. DSS occurred in 20.5% of the patients.
      Hemoconcentration and thrombocytopenia were observed in 91.5% and 92.5% of the
      patients, respectively. Serologic testing revealed that almost all of the
      patients (95.3%) had primary dengue virus infections. These data demonstrate that
      clinical and laboratory findings of DHF/DSS in infants are compatible with the
      World Health Organization's clinical diagnostic criteria for pediatric DHF. The
      present study is the first to report evidence of production of cytokines in
      infants with DHF/DSS and to describe the difference between the cytokine profile
      of infants with primary dengue virus infections and children with secondary
      infections. Overproduction of both proinflammatory cytokines (interferon-gamma
      and tumor necrosis factor-alpha) and anti-inflammatory cytokines (interleukin-10
      and -6) may play a role in the pathogenesis of DHF/DSS in infants.

PMID- 14722887
TI  - Risk factors for severe respiratory syncytial virus infection in elderly persons.
AB  - Risk factors for severe respiratory syncytial virus (RSV) infection were
      determined in 3 cohorts of adults during 2 consecutive winters (1999-2000 and
      2000-2001) in Rochester, New York. Community-dwelling healthy persons > or =65
      years old and persons >21 years old who had underlying symptomatic
      cardiopulmonary conditions were prospectively evaluated for RSV infection.
      Evidence of infection was also sought in persons who were > or =65 years old or
      had underlying cardiopulmonary disease and who were hospitalized with acute
      respiratory symptoms. Sixty-nine RSV infections were identified by culture,
      reverse-transcription polymerase chain reaction, or serologic testing in the
      prospective groups, and 61 were identified in the hospitalized group. The
      presence of underlying chronic pulmonary disease (odds ratio [OR], 3.97),
      functional disability (OR, 1.67/integer increase in Instruments of Activities of
      Daily Living score), and low serum neutralizing antibody titer (OR, 5.89) were
      each independently associated with increased risk of severe disease, defined as
      "hospitalization with RSV infection." These data suggest that the induction of
      neutralizing serum antibody with an RSV vaccine may potentially reduce disease
      severity in adult populations.

PMID- 14722888
TI  - Influence of promoter variants of interleukin-10, interleukin-9, and tumor
      necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.
AB  - Previously, we reported genetic associations between severe respiratory syncytial
      virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4
      and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of
      T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded
      our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis
      factor (TNF)-alpha, using both a transmission/disequilibrium test and a case
      control approach. Children homozygous for the IL-10 -592C or -592A allele had a
      higher risk of hospitalization for RSV bronchiolitis than did heterozygous
      carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66
      vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant
      association between RSV bronchiolitis and the IL-10 -592C allele was found (OR,
      1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9
      polymorphisms with RSV bronchiolitis were observed. We also explored the
      interactions between different polymorphisms and found an interaction between the
      IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.

PMID- 14722889
TI  - Hepatitis C virus-derived lipopeptides differentially induce epitope-specific
      immune responses in vitro.
AB  - We studied the induction of T cell responses against hepatitis C virus (HCV)
      related cytotoxic T cell (CTL) epitopes in lymphocytes from human leukocyte
      antigen (HLA)-A2-positive, HCV-naive individuals. Peptide and lipopeptides
      corresponding to the epitope at amino acids (aa) 1073-1081 induced equivalent
      numbers of tetramer-positive CD8+ T cells and detectable interferon-gamma and
      granzyme B spot-forming cells (sfcs). Epitope aa 35-44 induction of CTLs was not
      achieved, despite detectable tetramer-positive CD8+ T cells. IFN-gamma sfcs could
      only be induced with lipopeptide aa 20-44 but not by conventional antigens, which
      indicates that lipopeptides may alter T cell functions, depending on the epitope.

PMID- 14722890
TI  - Induction of cellular and humoral immunity after aerosol or subcutaneous
      administration of Edmonston-Zagreb measles vaccine as a primary dose to 12-month
      old children.
AB  - Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or
      subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles
      vaccine. Measles-specific T cell proliferative responses with a stimulation index
      of > or =3 developed in 72% of children given aerosol-administered vaccine,
      compared with 87% given s.c.-administered vaccine (P =.06). Seroconversion rates
      were 90% after aerosol-administered vaccine and 100% after s.c.-administered
      vaccine (P=.01), and measles geometric mean titers were 237 milli-international
      units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390
      609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell
      responses were weaker after aerosol than after sc vaccination, indicating a need
      to use a higher aerosol dose to achieve optimal immunogenicity.

PMID- 14722891
TI  - Protective efficacy of hepatitis E virus DNA vaccine administered by gene gun in
      the cynomolgus macaque model of infection.
AB  - The protective efficacy of a DNA vaccine against hepatitis E virus (HEV)
      infection was tested in cynomolgus macaques (cynos) vaccinated with a plasmid
      containing a full-length HEV open-reading frame 2 (ORF2) sequence (Burmese
      strain) and subsequently challenged with a heterologous strain of HEV (Mexican
      strain). Cynos administered vaccine by gene gun developed antibodies to HEV (anti
      HEV), whereas cynos administered vaccine by intradermal injections and cynos
      administered a mock DNA construct did not develop anti-HEV. Anti-HEV-positive
      cynos were protected from HEV infection after challenge with an inoculum that
      produced infection in the anti-HEV-negative cynos. These results indicate that
      DNA vaccine with HEV ORF2 administered by gene gun is protective against a
      heterologous viral challenge.

PMID- 14722892
TI  - Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV
      positive patients: a 48-week randomized clinical trial.
AB  - The safety, pharmacokinetics, and antiviral activity of lopinavir, a human
      immunodeficiency virus (HIV) protease inhibitor, coformulated with ritonavir as a
      pharmacokinetic enhancer were evaluated in 38 antiretroviral-naive patients
      randomized 1:1 to receive open-label lopinavir/ritonavir at a dose of 800/200 mg
      once daily or 400/100 mg twice daily, each in combination with stavudine and
      lamivudine twice daily, for 48 weeks. Over the course of 48 weeks, median predose
      concentrations of lopinavir exceeded the protein-binding corrected concentration
      required to inhibit replication of wild-type HIV by 50% in vitro by 40- and 84
      fold in the once- and twice-daily groups, respectively. Predose concentrations of
      lopinavir were more variable in the once-daily group (mean +/- SD, 3.62+/-3.38
      microg/mL for the once-daily group and 7.13+/-2.93 microg/mL for the twice-daily
      group). At week 48, in an intent-to-treat (missing = failure) analysis, 74% of
      patients in the once-daily group and 79% of patients in the twice-daily group had
      HIV RNA levels of <50 copies/mL (P=.70). Study drug-related discontinuations
      occurred in 1 patient in each treatment group. Genotypic resistance testing of 4
      patients with HIV RNA levels >400 copies/mL between weeks 24 and 48 demonstrated
      no protease inhibitor-resistance mutations.

PMID- 14722893
TI  - Attenuated and nonproductive viral transcription in the lymphatic tissue of HIV-1
      infected patients receiving potent antiretroviral therapy.
AB  - Human immunodeficiency virus type 1 (HIV-1) RNA that persists in the lymphoid
      tissue of patients despite treatment with highly active antiretroviral therapy
      (HAART) may represent extracellular virions or intracellular RNAs residing within
      HIV-infected cells. To further characterize residual viral transcription, tonsil
      biopsy specimens from patients receiving long-term HAART, untreated patients, and
      patients undergoing 2 weeks of structured treatment interruption were analyzed by
      polymerase chain reaction quantification of virion-encapsidated RNA,
      intracellular unspliced HIV RNA (HIV UsRNA), multiply spliced HIV RNA encoding
      tat and rev (HIV MsRNA), and HIV DNA. Tonsil biopsy specimens from viremic
      patients harbored high amounts of virions, which primarily stemmed from local
      production, as indicated by a strong correlation of extracellular tonsillar RNA
      with intracellular HIV-1 nucleic acid levels but not with plasma viremia, and as
      shown by phylogenetic analysis of clonal env sequences from lymphoid tissue and
      plasma. In patients receiving HAART, intracellular HIV UsRNA persisted at
      significantly decreased levels, whereas HIV MsRNA and lymphoid virion levels were
      depleted. Thus, residual lymphoid HIV-1 RNA in patients receiving HAART indicates
      attenuated viral transcription in HIV-1-infected cells that lack virion
      production.

PMID- 14722894
TI  - Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients
      infected with HIV type 1.
AB  - BACKGROUND: We wished to determine the safety and anti-human immunodeficiency
      virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4
      monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected
      subjects. METHODS: Sequential cohorts of 6 HIV-1-infected subjects each received
      infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4+ T cell count,
      TNX-355 coating of CD4+ T cells, and serum TNX-355 levels. RESULTS: Dose-related
      reductions in plasma HIV-1 RNA loads correlated with complete CD4+ T cell coating
      by TNX-355. Peak median decreases in plasma HIV-1 RNA loads were 0.56, 1.33, and
      1.11 log10 copies/mL and occurred on days 4-7, 14, and 21 for the 3.0, 10, and 25
      mg/kg doses, respectively. Dose-dependent increases in CD4+ T cell count occurred
      within 24 h of dosing. CONCLUSIONS: Single doses of TNX-355 reduced plasma HIV-1
      RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further
      assessment of therapeutic potential awaits data from longer-duration trials.

PMID- 14722895
TI  - Spread of hepatitis C virus among European injection drug users infected with
      HIV: a phylogenetic analysis.
AB  - To describe the spread of hepatitis C virus (HCV) among HCV/human
      immunodeficiency virus (HIV)-coinfected injection drug users (IDUs), the
      molecular epidemiology of HCV was studied among 108 IDUs from 7 European
      countries. Phylogenetic analysis based on the NS5B region showed great sequence
      variation of HCV within each country and no clear phylogenetic clustering by
      geographic region. The most prevalent subtypes were 1a and 3a, but the percentage
      of genotype 4 was also relatively high, ranging from 7% in northern Europe to 24%
      in southern Europe. Genotype 4 consisted mainly of subtype 4d and has entered the
      majority of the IDU populations studied. The significantly lower evolutionary
      distances within subtype 4d suggest that this subtype may have entered the
      European IDU population relatively recently. In conclusion, HCV exchange between
      European IDU populations has occurred on a large scale, and, overall, country
      specific clustering for HCV was less than that shown for HIV.

PMID- 14722896
TI  - Injectable contraceptive use and genital ulcer disease during the early phase of
      HIV-1 infection increase plasma virus load in women.
AB  - We examined the association between host factors present near the time of human
      immunodeficiency virus type 1 (HIV-1) acquisition and subsequent virus loads, in
      a prospective cohort study of women in Mombasa, Kenya. Women were prospectively
      followed monthly before HIV-1 infection. One hundred sixty-one commercial sex
      workers who became infected with HIV-1 were followed for a median of 34 months,
      and 991 plasma samples collected > or =4 months after infection were tested for
      HIV-1 RNA. The median virus set point at 4 months after infection was 4.46 log10
      copies/mL, and the average virus load increase during subsequent follow-up was
      0.0094 log10 copies/mL/month. In a multivariate analysis that controlled for
      sexual behavior, the use of the injectable contraceptive depot
      medroxyprogesterone acetate (DMPA) at the time of HIV-1 infection was associated
      with a higher virus set point, and the presence of genital ulcer disease (GUD)
      during the early phase of HIV-1 infection was associated with greater change in
      virus load during follow-up. These findings suggest that, in women, the use of
      DMPA and the presence of GUD during the early phase of HIV-1 infection may
      influence the natural course of infection.

PMID- 14722897
TI  - Strong cell-mediated immune responses are associated with the maintenance of low
      level viremia in antiretroviral-treated individuals with drug-resistant human
      immunodeficiency virus type 1.
AB  - Antiretroviral (ARV)-treated patients often maintain low to moderate levels of
      viremia, despite the emergence of drug-resistant human immunodeficiency virus
      (HIV). We studied host and viral factors that may contribute to the control of
      viral replication in a cohort of 189 adults. Among ARV-treated patients with
      detectable viremia, there was a bell-shaped relationship between Gag-specific
      CD4+ T cell responses and viremia, with the highest cellular immune responses
      observed in patients with plasma HIV RNA levels of 1000-10,000 copies/mL. In
      contrast, there was a negative association between Gag-specific CD4+ T cell
      responses and viremia among ARV-untreated individuals with wild-type HIV. Strong
      cellular immune responses among individuals with drug-resistant HIV predicted
      subsequent lack of virological progression. Finally, there was a positive
      correlation between replicative capacity and viremia. Collectively, these data
      suggest that the selection of drug-resistance mutations may reduce the pathogenic
      potential of HIV, which leads to a balanced state of enhanced cellular immunity
      and low-level viremia.

PMID- 14722898
TI  - Interclade neutralization and enhancement of human immunodeficiency virus type 1
      identified by an assay using HeLa cells expressing both CD4 receptor and
      CXCR4/CCR5 coreceptors.
AB  - We report on the development and evaluation of a human immunodeficiency virus
      (HIV) neutralization assay that uses P4P cells, which are CD4+CXCR4+CCR5+ HeLa
      cells that carry the lacZ gene under the control of the HIV-1 long terminal
      repeat. The results of the present study suggest that the P4P assay can be used
      for the extensive study of both neutralizing and enhancing activity in serum
      samples from HIV-1-infected patients and from vaccinated individuals.

PMID- 14722899
TI  - Capsular expression in Streptococcus pneumoniae negatively affects spontaneous
      and antibiotic-induced lysis and contributes to antibiotic tolerance.
AB  - Penicillin and vancomycin induce a lytic response in Streptococcus pneumoniae
      that requires the N-acetylmuramyl-l-alanine amidase LytA. We show that clinical
      isolates of pneumococci of capsular serotypes 1, 4, 6B, and 23F were generally
      less lytic to penicillin than pneumococci of serotypes 14 and 3. In addition,
      most 9V isolates were less lytic to vancomycin, compared with isolates of other
      serotypes. Parent-mutant pairs expressing and not expressing capsular serotypes
      2, 4, and 9V were compared for antibiotic-induced lysis. The nonencapsulated
      variants were considerably more lytic after beta-lactam and/or vancomycin
      treatment, and antibiotic tolerance was seen only in the context of capsule
      expression. Conversion from a nonlytic to a lytic phenotype, after loss of
      capsule expression, required an intact lytA autolysin gene. Exogenous addition of
      purified LytA gave a lower lytic response in capsulated strains, compared with
      that in nonencapsulated mutants. Spontaneous autolysis in stationary phase also
      was negatively affected by capsule expression in an autolysin-dependent manner.
      Long-term starvation in the stationary phase of the vancomycin- and penicillin
      tolerant isolate I95 yielded nonencapsulated mutants that had lost antibiotic
      tolerance and were lytic to penicillin and vancomycin. The 9V capsular locus of
      I95 and one of these stationary phase-selected mutants were completely sequenced.
      The only difference found was a 1-bp frameshift deletion in the cps9vE gene of
      the lytic mutant, encoding a uridine diphosphate-glucosyl-1-phosphate
      transferase. Two additional independently isolated lytic mutants of I95 from the
      stationary phase also contained mutations in the same region of cps9vE, which
      identified it as a mutational hot spot. This report demonstrates that capsular
      polysaccharides negatively influence the lytic process and contribute to
      antibiotic tolerance in clinical isolates of pneumococci.

PMID- 14722900
TI  - Effect of sex on Coxiella burnetii infection: protective role of 17beta
      estradiol.
AB  - Q fever is a zoonosis caused by Coxiella burnetii and recently has been
      recognized as a potential agent of bioterrorism. In Q fever, men are symptomatic
      more often than women, despite equal seroprevalence. We hypothesized that sex
      hormones play a role in the pathogenesis of C. burnetii infection. When C57/BL6
      mice were injected with C. burnetii, bacteria load and granuloma numbers were
      lower in females than in males. Ovarectomized mice showed increased bacteria load
      in the spleen and the liver, similar to that found in males. The granuloma number
      was also increased in ovarectomized mice and reached the levels found in males.
      Tissue infection and granulomatous response are largely under the control of
      estrogens: treatment of ovarectomized mice with 17beta-estradiol reduced both
      bacteria loads and granuloma numbers. These results show that sex hormones
      control host response to C. burnetii infection and may account for host-dependent
      clinical presentation of Q fever.

PMID- 14722901
TI  - Neutralization of Staphylococcus aureus Panton Valentine leukocidin by
      intravenous immunoglobulin in vitro.
AB  - Panton Valentine leukocidin (PVL) may be responsible for pulmonary necrosis in
      necrotizing Staphylococcus aureus pneumonia, a highly lethal infection.
      Commercial intravenous immunoglobulin (IVIg) preparations containing antibodies
      against PVL might have therapeutic value in this setting, as an adjunct to
      antimicrobial chemotherapy. To test this possibility, we determined anti-PVL
      antibody titers in commercial IVIg and the capacity of IVIg to prevent the
      cytopathic effects of PVL in vitro. Specific enzyme-linked immunosorbent assays
      based on purified recombinant PVL (rPVL) showed that IVIg contained specific anti
      PVL antibodies. The cytotoxicity of rPVL and of crude culture supernatants of PVL
      producing S. aureus strains were investigated by measuring ethidium-bromide
      incorporation by polymorphonuclear neutrophils (PMNs) in flow cytometric assays,
      as well as PMN ultrastructural changes by transmission electron microscopy. IVIg
      was found to neutralize pore formation and the cytopathic effect of both rPVL and
      S. aureus culture supernatants.

PMID- 14722903
TI  - Immunohistochemistry of matrix markers in Technovit 9100 New-embedded
      undecalcified bone sections.
AB  - Trabecular bone is routinely analysed by histomorphological-histometrical and
      immunohistochemical techniques as means of assessing the differentiation status
      of bone deposition and growth. Currently few embedding resins exist for which
      both morphological and immunohistochemical analyses can be performed on
      mineralised tissue. Paraffin, the standard embedding medium for bone enzyme and
      immunohistochemistry, can only be used on demineralised tissue, but then
      trabecular structure may be badly preserved. Methyl methacrylate (MMA), the resin
      of choice for undecalcified bone histology can only be used for bone
      immunohistochemistry if the usual, highly exothermic polymerisation procedure is
      avoided which destroys tissue antigenicity. Consequently, most current practices
      involve cutting samples in half to be processed in separate resins when more than
      one type of analysis is required. Technovit 9100 New is a low temperature MMA
      embedding system that is purported to significantly improve tissue antigenicity
      preservation allowing polymerisation at -20 degrees C. In this study, Technovit
      9100 New-embedded undecalcified trabecular bone samples (adult human, young
      bovine and ovine) yielded immunolabelling with several bone matrix markers and
      preserved morphological features in 7 microm sections when stained with Masson
      Goldner, von Kossa, or toluidine blue. Bone samples from all resins used were
      immunolabelled with antibodies against osteocalcin, alkaline phosphatase,
      osteopontin, osteonectin, bone sialoprotein and procollagen type I amino-terminal
      propeptide. Technovit-embedded bone yielded more reliable immunolabelling of the
      matrix proteins when compared with heat or cold-cured LR White or standard
      embedded MMA samples. Technovit 9100 New provided better routine histology than
      LR White, and was comparable to MMA. Results demonstrated that Technovit 9100 New
      can be used as a low-temperature acrylic resin embedding method for routine
      undecalcified bone histology, as well as for immunohistochemistry.

PMID- 14722904
TI  - Biophysical stimulation of bone fracture repair, regeneration and remodelling.
AB  - Biophysical stimulation to enhance bone fracture repair and bone regenerate
      maturation to restore its structural strength must rely on both the biological
      and biomechanical principle according to the local tissue environment and the
      type of mechanical stress to be born by the skeletal joint system. This paper
      reviews the possible interactions between biophysical stimuli and cellular
      responses in healing bone fractures and proceeds to speculate the prospects and
      limitations of different experimental models in evaluating and optimising such
      non-invasive interventions. It is important to realize that bone fracture repair
      has several pathways with various combinations of bone formation mechanisms, but
      there may only be one bone remodeling principle regulated by the hypothesis
      proposed by Wolff. There are different mechanical and biophysical stimuli that
      could provide effective augmentation of fracture healing and bone regenerate
      maturation. The key requirements of establishing these positive interactions are
      to define the precise cellular response to the stimulation signal in an in vitro
      environment and to use well-established animal models to quantify and optimise
      the therapeutic regimen in a time-dependent manner. This can only be achieved
      through research collaboration among different disciplines using scientific
      methodologies. In addition, the specific forms of biophysical stimulation and its
      dose effect and application timing must be carefully determined and validated.
      Technological advances in achieving focalized stimulus delivery with adjustable
      signal type and intensity, in the ability to monitor healing callus mechanical
      property non-invasively, and in the establishment of a robust knowledge base to
      develop effective and reliable treatment protocols are the essential pre
      requisites to make biophysical stimulation acceptable in the main arena of health
      care. Finally, it is important to bear in mind that successful fracture repair or
      bone regeneration through callus distraction without adequate remodeling process
      through physiological loading would seriously undermine the value of biophysical
      stimulation in meeting the biomechanical demand of a long bone.

PMID- 14722905
TI  - An electron microscopic and biochemical study of the effects of glucagon on
      glycogen autophagy in the liver and heart of newborn rats.
AB  - The effects of glucagon on the ultrastructural appearance and acid glucosidase
      activities in the liver and heart of newborn rats were studied. Liver or heart
      glycogen-hydrolyzing activity of acid glucosidase increased 3 hours after birth
      and gradually decreased from 3 to 9 hours. Maltose-hydrolyzing activity of acid
      glucosidase also rose 3 hours after birth, maintained a plateau between 3 and 6
      hours, and fell at 9 hours. The administration of glucagon increased autophagic
      activity in the hepatocytes at the age of 6 hours. Glycogen inside the autophagic
      vacuoles was decreased, apparently due to the increased glycogen degradation.
      Glycogen-hydrolyzing activity was elevated in both the liver and the heart.
      Maltose-hydrolyzing activity was elevated in the liver, but not in the heart. The
      results of this study suggest that the glycogen-hydrolyzing and maltose
      hydrolyzing activities of acid glucosidase are due to different enzymes.
      Glucagon's effect on the glycogen-hydrolyzing acid glucosidase activity and
      autophagosomal morphology is similar in both the liver and the heart.

PMID- 14722906
TI  - Age-dependent changes in the nervous and endocrine control of the thymus.
AB  - The immune system, especially the thymus, undergoes age-related modifications
      leading to structural and functional changes in the lymphoid organs and
      immunocompetent cells. Nevertheless, the consequences of thymic involution in the
      peripheral pool of T-cells are still a matter of controversy. The control of the
      thymic function is very complex and involves intrathymic signals, the autonomic
      nervous system, and the endocrine system. Both thymocytes and thymic stromal
      cells express receptors for a wide range of hormones, as well as for
      neurotransmitters and neuropeptides, thus affecting thymocytes maturation. This
      review summarizes the age-dependent variations in the extrathymic components of
      the thymic microenvironment, i.e., vegetative nerves and hormones, and the
      possible effects of those changes in the immune function.

PMID- 14722907
TI  - Simultaneous fixation using glutaraldehyde and osmium tetroxide or potassium
      ferricyanide-reduced osmium for the preservation of monogenean flatworms: an
      assessment for Merizocotyle icopae.
AB  - Simultaneous fixation was investigated for a marine organism: the monogenean
      flatworm ectoparasite Merizocotyle icopae. Four protocols for primary fixation
      were compared: 3% glutaraldehyde alone in 0.1M cacodylate buffer for a minimum of
      2 hours; 1% glutaraldehyde in combination with 1% osmium tetroxide, both in 0.1M
      cacodylate buffer, until tissues darkened (5-20 minutes); 1% glutaraldehyde in
      0.1M cacodylate buffer in combination with 0.5% potassium ferricyanide-reduced
      osmium until tissues darkened (5-20 minutes); 1% glutaraldehyde in combination
      with 1% osmium tetroxide, both in 0.1M cacodylate buffer, for 30 minutes. The
      study confirms that the standard method for transmission electron microscopic
      fixation (first listed protocol) routinely applied to platyhelminths is optimal
      for ultrastructural preservation, but some simultaneous fixation methods (second
      and third listed protocols) are acceptable when rapid immobilization is needed.
      Scanning electron microscopic preparations may be improved using simultaneous
      primary fixation.

PMID- 14722908
TI  - Cryo-sectioning and chemical-fixing ultramicrotomy techniques for imaging rubber
      latex particle morphology.
AB  - Two methods adapted from biological microscopy are described for a new
      application in imaging the morphology of rubbery latex particles. In the first
      method, a drop of latex is frozen in liquid nitrogen, sectioned with a diamond
      knife and vapour-stained with osmium tetroxide, then viewed by transmission
      electron microscopy. When applied to latexes made by emulsion polymerization of
      methyl methacrylate in a natural rubber latex seed, inclusions are clearly
      visible. A chemical fixation method is then described for imaging the morphology
      of such rubbery latex particles. Glutaraldehyde is added to the latex, followed
      by osmium tetroxide. The sample is then dehydrated in ethanol, epoxy resin added,
      and the sample cured, ultramicrotomed, and imaged with transmission electron
      microscopy. An inclusion morphology is again clearly seen.

PMID- 14722909
TI  - Imaging the cell surface: argon sputtering to expose inner cell structures.
AB  - Established microscopies such as Scanning Electron Microscopy (SEM) and more
      recent developments such as Atomic Force Microscopy (AFM) and X-ray Photo
      Electron Emission spectroMicroscopy (X-PEEM) can only image the sample surface.
      We present an argon sputtering method able to progressively expose inner cell
      structures without apparent damage. By varying the sputtering time, the structure
      of cell cytoskeleton, vesicles, mitochondria, nuclear membrane, and nucleoli can
      be imaged. We compared images obtained with confocal fluorescence microscopy,
      transmission electron microscopy (TEM), SEM, and X-PEEM on similar samples after
      argon sputtering, then confirmed the similarity of reference intracellular
      structures, including cytoskeleton fibers, cell-cell and cell-substrate adhesion
      structures, and secretory vesicles. We conclude that the sputtering method is a
      new valuable tool for surface sensitive microscopies.

PMID- 14722910
TI  - Methods for determining the composition of nasal fluid by X-ray microanalysis.
AB  - The nasal fluid is an easily accessible form of airway surface liquid. The
      objective of this study was to find a technically easy and reproducible method
      for sampling and analysis of this fluid. In a pilot study, several methods to
      carry out X-ray microanalysis of sub-microliter droplets were compared.
      Acceptable results were obtained with several of these methods (pipeting on
      filter paper or analysis of frozen-hydrated droplets at low temperature). Nasal
      fluid was collected from the inferior turbinate with a micropipette after
      occlusion of a nostril for 5-10 minutes. Ion concentrations in nasal fluid from
      six control subjects were (in mM, mean +/- standard error): sodium (Na) 127 +/-
      6, chloride (Cl) 140 +/- 7, potassium (K) 27 +/- 3, and calcium (Ca) 5 +/- 1.
      This sampling method proved difficult to apply to cystic fibrosis (CF) patients
      because of the viscous quality of their nasal secretion. Therefore, an
      alternative method was devised. Sephadex G-25, ion exchange beads were mounted on
      double-sided tape, which was stuck on a filter paper as support. The filter paper
      was applied for 10 minutes to the nostril of a subject, and kept loosely in
      place. During the exposure period, the nasal fluid equilibrates with the beads.
      After removal of the filter paper with the beads from the nostril, the beads were
      rinsed with a hydrophobic volatile silicone oil to remove excess nasal fluid,
      dried, and analyzed. This method of collection is not cumbersome for the subject
      and gives results similar to those obtained by the direct collection method: Na
      142 +/- 28 mM, Cl 150 +/- 36 mM, K 43 +/- 10 mM (mean and standard error of four
      determinations). Small differences between the filter method and the bead method
      can be explained by the fact that the filter method measured total nasal fluid,
      whereas the bead method measures predominantly the fluid component. Subjects
      suffering from mild respiratory illness or rhinitis had higher values for Na, K,
      and Cl in their nasal fluid.

PMID- 14722911
TI  - The transillumination possibility of imidazole-osmium postfixed muscle tissue and
      its consequences for the handling of muscle tissue samples.
AB  - The osmium postfixation of tissue leads to good results for transmission electron
      microscopy, but also produces completely blackened tissue samples that do not
      allow the recognition of internal structures. With imidazole-osmium postfixation,
      one achieves comparable results in high electron microscopic resolution as with
      routine osmium postfixation. But the tissue samples are not blackened and can,
      therefore, be transilluminated with point light sources. The new postfixation
      technique makes it possible to recognize histological details such as vessels,
      nerve fibers, and the cross-banding pattern in an untrimmed block. This makes it
      possible to screen-embedded tissue samples for appropriate ultrastructural
      processing.

PMID- 14722912
TI  - The pedigree tool: web-based visualization of a family tree.
AB  - We describe the development of a novel tool that facilitates the design and
      visualization of pedigrees using a special Internet application. The tool is
      programmed in Java, using a PHP script as an interface. This web-based tool is
      used to generate, edit, and/or view pedigrees. The advantage of our novel tool is
      that it is based on a notation that allows the representation of any given number
      of generations, family members per generation, and multiple clinical or genetic
      features of an individual family member. In addition, the notation allows us to
      minimize the storage space by 100% to 500% and to standardize the presentation of
      family trees and segregation analysis for inheritance of mendelian disorders or
      even complex traits. This pedigree tool has been implemented with a database of
      thyroid-stimulating hormone receptor (TSHR) mutations (http://www.uni
      leipzig.de/innere/tshr/).

PMID- 14722913
TI  - Mutations in the MATP gene in five German patients affected by oculocutaneous
      albinism type 4.
AB  - Oculocutaneous albinism (OCA) is caused by a deficiency of melanin synthesis and
      characterized by generalized hypopigmentation of skin, hair, and eyes. Due to the
      hypopigmentation of the retinal pigment epithelium, OCA is usually associated
      with congenital visual impairment, in addition to an increased risk of skin
      cancer. OCA is a genetically heterogeneous disease with distinct types resulting
      from mutations in different genes involved in the pathway which results in
      pigmentation. OCA1 is associated with mutations in the TYR gene encoding
      tyrosinase. OCA2 results from mutations in the P gene encoding the P protein and
      is the most common form of OCA. OCA3, also known as rufous/red albinism, is
      caused by mutations in the TYRP1 gene, which encodes the tyrosinase-related
      protein 1. Recently, OCA4 was described as a new form of OCA in a single patient
      with a splice site mutation in the MATP gene (or AIM1), the human ortholog of the
      murine underwhite gene. The similarity of MATP to transporter proteins suggests
      its involvement in transport functions, although its actual substrate is still
      unclear. We screened 176 German patients with albinism for mutations within the
      MATP gene and identified five individuals with OCA4. In this first report on West
      European patients, we describe 10 so far unpublished mutations, as well as two
      intronic variations, in addition to two known polymorphisms.

PMID- 14722914
TI  - Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1
      gene.
AB  - A total of 500 unselected unrelated neurofibromatosis 1 (NF1) patients were
      screened for deletions of the NF1 gene. After excluding 67 patients with known
      intragenic NF1 mutations, the remaining 433 were genotyped using six intragenic
      and one distal microsatellite marker for the NF1 gene. A total of 28 patients
      were hemi- or homozygous for all seven markers and were thus considered as
      candidates for NF1 deletion with a calculated probability of 99.99%. Metaphase or
      interphase cells were available from 23 of these 28 individuals for molecular
      cytogenetics. Fluorescence in situ hybridization (FISH) confirmed an NF1 deletion
      in 22 (96%) of the 23 patients. Thus, a constitutional deletion of the NF1 gene
      is responsible for the disease phenotype in at least 4.4% of the 500 unselected
      NF1 patients. Genotyping using multiple microsatellite markers may provide a
      simple, inexpensive, and efficient strategy for screening deletions of the NF1
      gene, and can as well be applied for other large genes.

PMID- 14722915
TI  - Y-chromosomal microsatellite mutation rates: differences in mutation rate between
      and within loci.
AB  - Precise estimates of mutation rates at Y-chromosomal microsatellite STR (short
      tandem repeat) loci make an important basis for paternity diagnostics and dating
      of Y chromosome lineage origins. There are indications of considerable locus
      mutation rate variability between (inter-) and within (intra-) loci. We have
      studied nine Y-STR loci-DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393,
      DYS385, and DYS388-in 1,766 father-son pairs of confirmed paternity (a total of
      15,894 meioses). Five biallelic markers were also analyzed in the fathers-Tat,
      YAP, 12f2, SRY1532, and 92R7-defining haplogroups 1, 2, 3, 4, 9, and 16,
      respectively. A total of 36 fragment length mutations were observed: 24 gains (22
      single-step, two double-step) and 12 single-step losses. Thus, there was a
      significant surplus of gains (p=0.045). Overall, the mutation rate was positively
      correlated to STR repeat length and there was a significant relative excess of
      losses in long alleles and gains in short alleles (p=0.043). In contrast to the
      situation in autosomal STR loci and in MSY-1, no noteworthy correlation between
      mutation rate and the father's age at the child's birth was observed. We observed
      significant interlocus differences in Y-STR mutation rates (p<0.01). The number
      of observed mutations ranged from zero in DYS392 to eight in DYS391 and DYS390.
      We have also demonstrated obvious differences in mutation rates between the
      haplogroups studied (p=0.024), a phenomenon that is a reflection of the
      dependence of mutation rate on allele size. Our study has thus demonstrated the
      necessity of not only locus-specific, but even allele-specific, mutation rate
      estimates for forensic and population genetic purposes, and provides a
      considerable basis for such estimates.

PMID- 14722916
TI  - Mitochondrial DNA-like sequences in the nucleus (NUMTs): insights into our
      African origins and the mechanism of foreign DNA integration.
AB  - Nuclear mitochondrial DNA sequences (NUMTs) are common in eukaryotes. However,
      the mechanism by which they integrate into the nuclear genome remains a riddle.
      We analyzed 247 NUMTs in the human nuclear DNA (nDNA), along with their flanking
      regions. This analysis revealed that some NUMTs have accumulated many changes,
      and thus have resided in the nucleus a long time, while others are >94% similar
      to the reference human mitochondrial DNA (mtDNA), and thus must be recent. Among
      the latter, two NUMTs, encompassing the COI gene, carry a set of transitions
      characteristic of the extant African-specific L macrohaplogroup mtDNAs and are
      more homologous to human mtDNA than to chimp. Screening for one of these NUMTs
      revealed its presence in all human samples tested, confirming that the African
      macrohaplogroup L mtDNAs were present in the earliest modern humans and thus were
      the first human mtDNAs. An analysis of flanking sequences of the NUMTs revealed
      that 59% were within 150 bp of repetitive elements, with 26% being within 15 bp
      of and 33% being within 15-150 bp of repetitive elements. Only 14% were
      integrated into a repetitive element. This association of NUMTs with repetitive
      elements is highly nonrandom (p<0.001). These data suggest that the vicinity of
      transposable elements influences the ongoing integration of mtDNA sequences and
      their subsequent duplication within the nDNA. Finally, NUMTs appear to
      preferentially integrate into DNA with different GC content than the surrounding
      chromosomal band. Our results suggest that chromosomal structure might influence
      integration of NUMTs.

PMID- 14722917
TI  - Characterization of the somatic mutational spectrum of the neurofibromatosis type
      1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors.
AB  - One of the main features of neurofibromatosis type 1 (NF1) is benign
      neurofibromas, 10-20% of which become transformed into malignant peripheral nerve
      sheath tumors (MPNSTs). The molecular basis of NF1 tumorigenesis is, however,
      still unclear. Ninety-one tumors from 31 NF1 patients were screened for gross
      changes in the NF1 gene using microsatellite/restriction fragment length
      polymorphism (RFLP) markers; loss of heterozygosity (LOH) was found in 17 out of
      91 (19%) tumors (including two out of seven MPNSTs). Denaturing high performance
      liquid chromatography (DHPLC) was then used to screen 43 LOH-negative and 10 LOH
      positive tumors for NF1 microlesions at both RNA and DNA levels. Thirteen
      germline and 12 somatic mutations were identified, of which three germline (IVS7
      2A>G, 3731delT, 6117delG) and eight somatic (1888delG, 4374-4375delCC, R2129S,
      2088delG, 2341del18, IVS27b-5C>T, 4083insT, Q519P) were novel. A mosaic mutation
      (R2429X) was also identified in a neurofibroma by DHPLC analysis and
      cloning/sequencing. The observed somatic and germline mutational spectra were
      similar in terms of mutation type, relative frequency of occurrence, and putative
      underlying mechanisms of mutagenesis. Tumors lacking mutations were screened for
      NF1 gene promoter hypermethylation but none were found. Microsatellite
      instability (MSI) analysis revealed MSI in five out of 11 MPNSTs as compared to
      none out of 70 neurofibromas (p=1.8 x 10(-5)). The screening of seven MPNSTs for
      subtle mutations in the CDKN2A and TP53 genes proved negative, although the
      screening of 11 MPNSTs detected LOH involving either the TP53 or the CDKN2A gene
      in a total of four tumors. These findings are consistent with the view that NF1
      tumorigenesis is a complex multistep process involving a variety of different
      types of genetic defect at multiple loci.

PMID- 14722918
TI  - Mutations of ARX are associated with striking pleiotropy and consistent genotype
      phenotype correlation.
AB  - We recently identified mutations of ARX in nine genotypic males with X-linked
      lissencephaly with abnormal genitalia (XLAG), and in several female relatives
      with isolated agenesis of the corpus callosum (ACC). We now report 13 novel and
      two recurrent mutations of ARX, and one nucleotide change of uncertain
      significance in 20 genotypic males from 16 families. Most had XLAG, but two had
      hydranencephaly and abnormal genitalia, and three males from one family had Proud
      syndrome or ACC with abnormal genitalia. We obtained detailed clinical
      information on all 29 affected males, including the nine previously reported
      subjects. Premature termination mutations consisting of large deletions,
      frameshifts, nonsense mutations, and splice site mutations in exons 1 to 4 caused
      XLAG or hydranencephaly with abnormal genitalia. Nonconservative missense
      mutations within the homeobox caused less severe XLAG, while conservative
      substitution in the homeodomain caused Proud syndrome. A nonconservative missense
      mutation near the C-terminal aristaless domain caused unusually severe XLAG with
      microcephaly and mild cerebellar hypoplasia. In addition, several less severe
      phenotypes without malformations have been reported, including mental retardation
      with cryptogenic infantile spasms (West syndrome), other seizure types, dystonia
      or autism, and nonsyndromic mental retardation. The ARX mutations associated with
      these phenotypes have included polyalanine expansions or duplications, missense
      mutations, and one deletion of exon 5. Together, the group of phenotypes
      associated with ARX mutations demonstrates remarkable pleiotropy, but also
      comprises a nearly continuous series of developmental disorders that begins with
      hydranencephaly, lissencephaly, and agenesis of the corpus callosum, and ends
      with a series of overlapping syndromes with apparently normal brain structure.

PMID- 14722919
TI  - Genetic characterization and structural analysis of VHL Spanish families to
      define genotype-phenotype correlations.
AB  - Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by
      germline mutations in the VHL gene. This gene, located in the 3p25-26 chromosome,
      is a tumor suppressor gene associated with the inhibition of angiogenesis and
      apoptosis, cell cycle exit, fibronectin matrix assembly, and proteolysis. To
      define the molecular basis of VHL in a Spanish population, we studied 33 patients
      suspected of suffering familial or de novo VHL disease and two familial
      pheochromocytoma cases. Sequence analysis of the coding regions of the VHL gene
      revealed germline sequence variants in 68.7% (24 out of 35) of the patients, and
      four of them presented with undescribed germline alterations: g.5429-5430insG,
      p.Leu128Arg, p.Tyr175Cys, and p.Tyr175Asn. For the remaining 11 patients who
      showed negative for point mutations, we performed Southern blot analysis and
      detected gross rearrangements in eight cases (22.8% of the index cases). Our
      results support the relevance of VHL gene analysis in familial pheochromocytoma
      cases and also in those with no familial history. In order to investigate the
      relevance of different amino acid changes in the VHL phenotype, we also analyzed
      the genotype-phenotype correlations using structural analysis to assess protein
      stability and complexes. The association of clear cell renal carcinoma (CCRC)
      development with a relatively high loss of structural stability in pVHL missense
      mutants was consistent. Structural stability data in the genotype-phenotype
      correlations therefore provides us with a better understanding of VHL clinical
      implications. It is also a suitable approach to the evaluation of unknown
      significance changes.

PMID- 14722920
TI  - Loss of function of the cytoplasmic isoform of the protein laforin (EPM2A) causes
      Lafora progressive myoclonus epilepsy.
AB  - Lafora disease is the most severe teenage-onset progressive epilepsy, a unique
      form of glycogenosis with perikaryal accumulation of an abnormal form of
      glycogen, and a neurodegenerative disorder exhibiting an unusual generalized
      organellar disintegration. The disease is caused by mutations of the EPM2A gene,
      which encodes two isoforms of the laforin protein tyrosine phosphatase, having
      alternate carboxyl termini, one localized in the cytoplasm (endoplasmic
      reticulum) and the other in the nucleus. To date, all documented disease
      mutations, including the knockout mouse model deletion, have been in the segment
      of the protein common to both isoforms. It is therefore not known whether
      dysfunction of the cytoplasmic, nuclear, or both isoforms leads to the disease.
      In the present work, we identify six novel mutations, one of which, c.950insT
      (Q319fs), is the first mutation specific to the cytoplasmic laforin isoform,
      implicating this isoform in disease pathogenesis. To confirm this mutation's
      deleterious effect on laforin, we studied the resultant protein's subcellular
      localization and function and show a drastic reduction in its phosphatase
      activity, despite maintenance of its location at the endoplasmic reticulum.

PMID- 14722921
TI  - Context of deletions and insertions in human coding sequences.
AB  - We studied the dependence of the rate of short deletions and insertions on their
      contexts using the data on mutations within coding exons at 19 human loci that
      cause mendelian diseases. We confirm that periodic sequences consisting of three
      to five or more nucleotides are mutagenic. Mutability of sequences with strongly
      biased nucleotide composition is also elevated, even when mutations within
      homonucleotide runs longer than three nucleotides are ignored. In contrast, no
      elevated mutation rates have been detected for imperfect direct or inverted
      repeats. Among known candidate contexts, the indel context GTAAGT and regions
      with purine-pyrimidine imbalance between the two DNA strands are mutagenic in our
      sample, and many others are not mutagenic. Data on mutation hot spots suggest two
      novel contexts that increase the deletion rate. Comprehensive analysis of
      mutability of all possible contexts of lengths four, six, and eight indicates a
      substantially elevated deletion rate within YYYTG and similar sequences, which is
      one of the two contexts revealed by the hot spots. Possible contexts that
      increase the insertion rate (AT(A/C)(A/C)GCC and TACCRC) and decrease deletion
      (TATCGC) or insertion (GCGG) rates have also been identified. Two-thirds of
      deletions remove a repeat, and over 80% of insertions create a repeat, i.e., they
      are duplications.

PMID- 14722922
TI  - Novel TP53 gene mutations in tumors of Russian patients with breast cancer
      detected using a new solid phase chemical cleavage of mismatch method and
      identified by sequencing.
AB  - Mutations in the tumor-suppressor p53 gene TP53 are frequent in most human
      cancers including breast cancer. A new solid phase chemical cleavage of mismatch
      method (CCM) allowed rapid and efficient screening and analysis of the TP53 gene
      in DNA samples extracted from tumors of 89 breast cancer patients. The novel CCM
      technique utilized silica beads and the potassium permanganate/tetraethylammonium
      chloride (KMnO(4)/TEAC) and hydroxylamine (NH(2)OH) reactions were performed
      sequentially in a single tube. Mutation analysis involved amplification of five
      different fragments of the TP53 gene using DNA from the 89 tumor samples, then
      pairing of the 391 labeled PCR products and forming heteroduplexes. A total of 41
      unique signals were revealed in the analysis of TP53 exons 5-9 and eight were
      identified by direct sequencing. The three novel mutations detected are c.600T>G
      (p.Asn200Lys), c.601T>G (p.Leu201Val), and c.766-768delACA (p.Thr256del). The
      detected mutations c.638G>T (p.Arg213Leu), c.730G>T (p.Gly244Cys), and c.758C>T
      (p.Thr253Ile) have not been reported in breast cancer but have been recorded in
      tumors of other organs. A previously reported mutation c.535C>T (p.His179Tyr) and
      a heterozygous polymorphism c.639A>G were also detected. Of the 41 unique
      signals, 36 were not identified as a sequence change. As direct sequencing
      requires the mutant allele concentration to be greater than 30% when the mutant
      allele is present in a mixture with the wild-type allele, the CCM method
      represents a more sensitive technique requiring a lower mutant allele
      concentration in the wild-type mixture compared with direct sequencing. This
      reveals the advantage of CCM for unknown point mutation detection in DNA samples
      of cancer patients.

PMID- 14722923
TI  - Comprehensive screening for constitutional RB1 mutations by DHPLC and QMPSF.
AB  - Constitutional mutations of the RB1 gene are associated with a predisposition to
      retinoblastoma. It is essential to identify these mutations to provide
      appropriate genetic counseling in retinoblastoma patients, but this represents an
      extremely challenging task, as the vast majority of mutations are unique and
      spread over the entire coding sequence. Since 2001, we have implemented RB1
      testing on a routine basis as part of the clinical management of retinoblastoma.
      As most screening techniques do not meet the requirements for efficient RB1
      testing, we have devised a semi-automated denaturing high-performance liquid
      chromatography (DHPLC) method for point mutation detection combined with a
      quantitative multiplex PCR of short fluorescent fragments (QMPSF) approach to
      screen for gene rearrangements. We report the results of this comprehensive
      screening of all exons and promoter of RB1 in 192 unrelated patients, mostly of
      French origin. Among 102 bilateral and/or familial cases and 90 unilateral
      sporadic probands, mutations were identified in 83 (81.5%) and 5 (5.5%) cases,
      respectively. A total of 43 mutations have not been previously reported. The
      mutational spectrum was found to be significantly different from previous
      published series, displaying a surprising amount of splice mutations and large
      deletions. This study demonstrates the reliability of DHPLC for RB1 analysis, but
      also illustrates the need for a deletion scanning approach. Finally, considering
      the benefits to retinoblastoma patients, RB1 testing should be widely implemented
      in routine healthcare because our study clearly illustrates its feasibility.

PMID- 14722924
TI  - Three-tiered noninvasive diagnosis in 96% of patients with Duchenne muscular
      dystrophy (DMD).

PMID- 14722925
TI  - Two novel severe mutations in the pancreatic secretory trypsin inhibitor gene
      (SPINK1) cause familial and/or hereditary pancreatitis.
AB  - Mutations in the serine protease inhibitor Kazal type 1 gene (SPINK1) encoding
      pancreatic secretory trypsin inhibitor (PSTI) have recently been found to be
      associated with chronic pancreatitis. Nevertheless, knowledge of severe mutations
      is particularly scarce, both in terms of number and in the extent of clinical
      information. The aim of this study was to expand the known spectrum of such
      mutations. 46 unrelated families, each including at least two pancreatitis
      patients and carrying neither cationic trypsinogen (PRSS1) mutations nor the
      frequent SPINK1 N34S mutation, participated in this study. The four exons and
      their flanking sequences of the SPINK1 gene were screened by denaturing high
      performance liquid chromatography analysis (DHPLC); and mutations were identified
      by direct sequencing. A heterozygous microdeletion mutation (c.27delC), which
      occurs within a symmetric element, was identified in two families. In one family,
      c.27delC showed segregation with the disease across two generations, with a
      penetrance of up to 75%. But in the other family, however, the same mutation
      manifested as a low-penetrance susceptibility factor. In addition, a novel
      heterozygous splicing mutation, c.87+1G>A (G>A substitution at nucleotide +1 of
      intron 2) was found in one family with familial pancreatitis. Our results also
      helped to resolve the sharply differing views about PSTI's role in pancreatitis.

PMID- 14722926
TI  - Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast
      ovarian cancer families.
AB  - The two major hereditary breast/ovarian cancer predisposition tumor suppressor
      genes, BRCA1 and BRCA2 that perform apparently generic cellular functions
      nonetheless cause tissue-specific syndromes in the human population when they are
      altered, or mutated in the germline. However, little is known about the
      contribution of BRCA1 and BRCA2 mutations to breast and/or ovarian cancers in the
      Indian population. We have screened for mutations the entire BRCA1 and BRCA2
      coding sequences, and intron-exon boundaries, as well as their flanking intronic
      regions in sixteen breast or breast and ovarian cancer families of Indian origin.
      We have also analyzed 20 female patients with sporadic breast cancer regardless
      of age and family history, and 69 unrelated normal individuals as control. Thus a
      total of 154 samples were screened for BRCA1 and BRCA2 mutations using a
      combination of polymerase chain reaction-mediated site directed mutagenesis
      (PSM), polymerase chain reaction-single stranded conformation polymorphism assay
      (PCR-SSCP) and direct DNA sequencing of PCR products (DS). Twenty-one sequence
      variants including fifteen point mutations were identified. Five deleterious
      pathogenic, protein truncating frameshift and non-sense mutations were detected
      in exon 2 (c.187_188delAG); and exon 11 (c.3672G>T) [p.Glu1185X] of BRCA1 and in
      exon 11 (c.5227dupT, c.5242dupT, c.6180dupA) of BRCA2 (putative mutations - four
      novel) as well as fourteen amino acid substitutions were identified. Twelve BRCA1
      and BRCA2 missense variants were identified as unique and novel. In the cohort of
      20 sporadic female patients no mutations were found.

PMID- 14722927
TI  - The molecular basis of cystathionine beta-synthase (CBS) deficiency in UK and US
      patients with homocystinuria.
AB  - The molecular basis of cystathionine beta-synthase (CBS) deficiency has been
      studied in 536 patient alleles with 130 different mutations described. To date,
      no study has reported on the incidence of any of the reported mutations in
      patients from the UK and the US. We developed a new antisense oligonucleotide
      (ASO) PCR/hybridization method to screen for 12 of the most frequent CBS
      mutations in 14 unrelated patients from the UK and 38 unrelated patients from the
      US, a total of 104 independent alleles. We determined 16/28 (57%) and 28/76 (37%)
      of the affected alleles in the UK and US patients, respectively. Four different
      mutations were identified in the UK patients (c.374G>A, R125Q; c.430G>A, E144K;
      c.833T>C, I278T; c.919G>A, G307S) and 8 mutations identified in the patients from
      the US (c.341C>T, A114V; c.374G>A, R125Q; c.785C>T, T262M; c.797G>A, R266K;
      c.833T>C, I278T; c.919G>A, G307S; g.13217A>C (del ex 12); c.1330G>A, D444N). The
      I278T was the predominant mutation in both populations, present in 8 (29%) of 28
      independent alleles from the UK and in 14 (18%) of 76 independent alleles from
      the US. The incidence of the G307S mutation was 21% in the UK patients and 8% in
      the US patients. The spectrum of mutations observed in the patients from the UK
      and US is closer to that which is observed in Northern Europe and bears less
      resemblance to that observed in Ireland.

PMID- 14722928
TI  - Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency
      and a founder effect for the R241C mutation.
AB  - The spectrum of phenylalanine hydroxylase (PAH) gene mutations was determined in
      25 families of hyperphenylalaninemia identified by a neonatal screening program
      in Taiwan. The coding sequence and exon-flanking intron sequences of PAH gene
      were amplified and sequenced. Mutations were identified in forty-five of the 50
      chromosomes. R241C was the most common mutation (36% of the chromosomes),
      followed by R408Q (14% of the chromosomes). The remaining mutations were rare and
      seven mutations have not been reported before: p.F233L (c.697T>C), p.R252Q
      (c.756G>A), p.E286K (c.856G>A), p.G312V (c.935G>T), p.P314T (c.940C>A), p.I95del
      (c.284_286delTCA), and p.T81fsX6 (c.241_256del). Both p.R241C and p.R408Q are
      classified as mild phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP)
      mutation, which may explain the fact that classical PKU is very rare in Taiwan
      (n=4, or one in 413,035). This strong founder effect for the p.R241C mutation has
      been described neither in the Caucasian populations, nor in other reports from
      Chinese. Since most of the populations in Taiwan are derived from Southeastern
      China, the spectrum of PAH gene mutations in Southeastern China should be
      different from other Chinese populations. This report not only disclose a
      specific spectrum of PAH gene mutation in Taiwan, but may also give clues to the
      movement of populations in Mainland China.

PMID- 14722929
TI  - Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel
      GJB2 variants.
AB  - A large proportion of non-syndromic autosomal recessive deafness (NSARD) in many
      populations is caused by variants of the GJB2 gene. Here, the frequency of GJB2
      variants was studied in 406 and 183 apparently unrelated children from Kenya and
      Sudan, respectively, with mostly severe to profound non-syndromic deafness. Nine
      (2.2 %) Kenyan and 12 (6.6 %) of the Sudanese children only were carriers of
      variants within the coding sequence of the GJB2 gene. Variants in the 5'-adjacent
      region were detected in further 115 individuals. A total of 10 novel variants was
      recognized, among them four variants in the adjacent 5'-region of the GJB2 coding
      exon 2 (g.3318-6T>A, g.3318-15C>T, g.3318-34C>T, g.3318-35T>G), a 6 base-pair
      deletion (g.3455_3460del [p.Asp46_Gln48delinsGlu]), a variant leading to a stop
      codon (g.3512C>A [p.Tyr65X]), synonymous variants (g.3395C>T [p.Thr26], g.3503C>T
      [p.Asn62], g.3627A>C [p.Arg104]), and one non-synonymous variant (g.3816C>A
      [p.Val167Met]). In addition, the previously described variants g.3352delG
      (commonly designated 30delG or 35 delG), g.3426G>A [p.Val37Ile], g.3697G>A
      [p.Arg127His], g.3774G>A [p.Val153Ile], and g.3795G>A [p.Gly160Ser] were
      identified. With the exception of g.3318-34C>T and g.3352delG, all variants
      occurred heterozygously. For most of the variants identified in the Kenyan and
      Sudanese study population, a causative association with NSARD appears to be
      unlikely. Compared to many other ethnic groups, deafness-associated variants of
      the coding region of GJB2 are rare in Sudan and Kenya, suggesting a role of other
      genetic, or epigenetic factors as a cause for deafness in these countries.

PMID- 14722930
TI  - On the front lines.

PMID- 14722931
TI  - Pediatric preventive health screenings: rules change but physician responsibility
      remains.

PMID- 14722932
TI  - Cutis aplasia of the scalp: three cases in eighteen months.
AB  - Three patients with cutis aplasia of the scalp presented to Arkansas Children's
      Hospital over a period of eighteen months. Two of the patients required operative
      intervention for closure of the defects and the third patient healed with
      dressing changes. Surgery required the combined efforts of both neurosurgery and
      plastic surgery.

PMID- 14722933
TI  - Early childhood screening by primary care physicians.

PMID- 14722934
TI  - Case of the month. A case report of human pulmonary dirofilariasis in Arkansas.
AB  - Our patient, a resident of Arkansas, presented with a solitary pulmonary nodule
      for lung resection to rule out primary lung cancer. However, pathologic
      examination showed the lung nodule to be a granuloma secondary to dirofilariasis.
      Human pulmonary dirofilariasis is a rare zoonotic disease caused by
      Dirofilariasis immitis (dog heartworm) that is usually transmitted from dogs to
      human by mosquito bite. To our knowledge, human pulmonary dirofilariasis has
      previously not been reported in Arkansas. In addition, awareness of this entity
      in the appropriate clinical and epidemiologic setting is important in the
      differential diagnosis of solitary pulmonary nodules.

PMID- 14722936
TI  - [Efficacy of ofloxacin (zanocin) in the treatment of multidrug resistant
      pulmonary tuberculosis].
AB  - Data concerning chemotherapy of patients with multiresistant tuberculosis of the
      lungs by reserve antituberculous agents in combination with ofloxacin are
      presented. It was shown that the ofloxacin-including chemotherapy regimen applied
      to patients with multiresistant destructive tuberculosis of the lungs provided by
      the end of the 6-month treatment course elimination of multidrug resistant
      tubercle bacilli isolation at least in 80% of the patients and closure of the
      lung caverns after artificial pneumothorax and routine surgical interventions in
      more than half of the patients. For all this, side effects that could not be
      eliminated were stated merely in 8.5% of the patients.

PMID- 14722935
TI  - [Screening of natural immunosuppressors by their ability to modify steroid
      synthesis in hepatocytes].
AB  - In the programme for screening sterol synthesis inhibitors with the use of
      actinomycetes and fungi 702 strains were tested. The effect of alcohol extracts
      of the mycelium of fungi and actinomycetes at a dilution of 1/10(3) on sterol
      synthesis by the Hep G2 hepatome cells was determined by incorporation of 3H
      acetate into sterols and proteins. Lovastatin (200 pg/ml) was used as the
      control: the sterol synthesis was decreased by 49 +/- 4% without inhibiting the
      protein synthesis. A number of the cultures produced compounds inhibiting under
      the experimental conditions the synthesis of sterols by 70 to 80% with
      simultaneous inhibition of the protein synthesis at least by 60 to 70%. Three
      compounds from that group produced by streptomycetes were subjected to a more
      detailed investigation. The compounds were demonstrated to be active antifungal
      antibiotics (MIC 0.1-1 mcg/ml). In a dose of 0.1-1 mcg/ml they showed high
      immunosuppressive activity in models of lymphocyte transformation in mice,
      whereas cyclosporin was active in a dose of 1 mcg/ml. Therefore, the model for
      screening hypolipidemic compounds could be considered useful for screening
      promising natural immunosuppressors.

PMID- 14722937
TI  - [Linezolid for the treatment of nosocomial infections after cardiac surgery].
AB  - Clinical and bacteriological efficacy of linezolid in the treatment of
      cardiosurgical patients with various localization nosocomial infections due to
      problem grampositive cocci was estimated. The group included 10 patients:
      children at the age 3 months to 12 years (n = 3) and adults at the age of 17 to
      65 years (n = 7) with infectious complications such as infectious endocarditis (n
      = 4), pneumonia (n = 2), wound infection (n = 3) and sepsis (n = 1). All the
      patients isolated MR staphylococci. The use of glycopeptides was not possible in
      6 patients because of vancomycin intolerance (n = 1), renal insufficiency (n = 1)
      and failure of the previous vancomycin therapy (n = 4). To all the patients
      linezolid was administered per os (tablets or suspension) or intravenously
      (infusion solution) in doses of 600 mg twice a day (1200 mg a day) for the adults
      and 10 mg/kg body weight every 12 hours (20 mg/kg body weight a day) for the
      children. Linezolid monotherapy was applied to 2 patients. 8 patients were
      treated with linezolid in combination with some other antibiotics. By the
      clinical findings the positive dynamics confirmed by thermometry and hemograms
      was observed in 8 patients beginning from the 4th day of the linezolid use.
      Eradication of MR staphylococci from the blood, sputum and wounds was stated in
      all 10 patients. No toxic or adverse reactions were noted. It was concluded that
      linezolid is an optimal alternative to vancomycin especially when the use of the
      latter is not possible. No nephrotoxic effects of linezolid provided its
      recommendation as a drug of choice in the treatment of patients with renal
      disturbances, including polyorganic insufficiency.

PMID- 14722938
TI  - [Antibacterial therapy of sepsis in children].

PMID- 14722939
TI  - [Treatment of drug resistant tuberculosis].

PMID- 14722940
TI  - [Side effects of systemic antimycotics].

PMID- 14722941
TI  - [Thrombin-like serine proteases in Cerasted venoms (Cerasted cerastes and
      Cerastes vipera)].
AB  - Cerastes cerastes and Cerastes vipera snake venoms are rich of thrombin-like,
      serine-protease polypeptides. Many proteins have been isolated, purified and
      characterized from these vipers. These proteins act in various way on blood
      coagulation pathway and platelet function.

PMID- 14722942
TI  - [Mitochondrial DNA polymorphism reveals a genetic differentiation between ethnic
      groups in the population of Jerba].
AB  - Jerba is an island situated in the South-East of Tunisia were some ethnic groups
      (Arabs, Berbers, Blacks, Jewishs and others) cohabit for centuries. The religion
      and cultural differences have represented an obstacle to a mixture between these
      groups. In order to evaluate the genetic differentiation between the muslim
      groups (Arabs, Berbers and Blacks), we have analysed the polymorphism of a
      mitochondrial DNA coding region. The cytochrome oxydase coding region (COII) was
      amplified by PCR in 57 Arabs, 42 Berbers and 16 Blacks. The amplified products
      were analysed by Restriction Fragment Length Polymorphism (RFLP). Genetic
      distances were calculated by using the AMOVA program. The values of these
      distances were significantly different between Arabs and Blacks, and between
      Berbers and Blacks but not between Arabs and Berbers. So That, to refine the
      evaluation of genetic diversity between Arabs and Berbers, we have analysed the
      polymorphism of a second mitochondrial coding region which encodes for the fifth
      unit of NADH deshydrogenase (ND5). Eleven haplotypes were defined from the
      resulting data of mitochondrial COII and ND5 polymorphism and a significant
      genetic distance between Arabs and Berbers was computed.

PMID- 14722943
TI  - Cutaneous leishmaniasis in Al-Badarna: a prospective study among school children.
AB  - This paper presents the results of a prospective study cutaneous liashmaniasis in
      2 schools in Al-Badarna, during the period from July to December 1992. The pupils
      were interviewed and examined. Positive cases were referred to the Health Unit
      for treatment. Of 260 pupils 22 (8.46%) were found to be infected with active
      lesions.

PMID- 14722944
TI  - Fat pill for teens. Xenical may have the FDA's blessing, but is it a good idea?

PMID- 14722945
TI  - High-throughput parallel LC/UV/MS analysis of combinatorial libraries.

PMID- 14722946
TI  - Qualitative colorimetric tests for solid phase synthesis.
AB  - Results obtained in the application of these tests are summarized in Table II. We
      have encountered some variations in the reproducibility and accuracy of some
      tests. Due to the numerous factors that can influence colorimetric test results
      (e.g., test reagent stability, resin type, functional group interference, and
      lability of protecting group) we highly recommend performing a positive and a
      negative control for any test applied to a new synthesis. We also emphasize the
      importance of reagent solution purity on the outcome of test results, hence we
      strongly encourage the use of correctly prepared and carefully stored reactants.
      To minimize false results due to lability of the resin-product bond or the
      product itself (such as Fmoc-protected amino acids), colorimetric tests should be
      performed with the utmost immediacy in regards to completion of the step to be
      monitored. Hence the storage of resin over long periods of time (more than 24 h)
      before testing is not advisable. When the result of a colorimetric test is in
      doubt we advise repeating the test a few times until a reproducible result is
      obtained. The use of multiple tests for the same functional group may elucidate
      ambiguous or otherwise challenging cases.

PMID- 14722947
TI  - A review of solid-phase organic synthesis on SynPhase Lanterns and SynPhase
      Crowns.

PMID- 14722948
TI  - Directed sorting approach for the synthesis of large combinatorial libraries of
      discrete compounds.

PMID- 14722949
TI  - Split-mix synthesis using macroscopic solid support units.

PMID- 14722950
TI  - The encore technique: a novel approach to directed split-and-pool combinatorial
      synthesis.

PMID- 14722951
TI  - Multifunctional linkers as an efficient tool for the synthesis of diverse small
      molecule libraries: the triazene anchors.

PMID- 14722952
TI  - The development and application of tetrafluorophenol-activated resins for rapid
      amine derivatization.

PMID- 14722953
TI  - The traceless solid-phase synthesis of organic molecules.

PMID- 14722954
TI  - Unnatural diamino acid derivatives as scaffolds for creating diversity and as
      linkers for simplifying screening in chemical libraries.

PMID- 14722955
TI  - Building dihydropyrimidine libraries via microwave-assisted Biginelli
      multicomponent reactions.

PMID- 14722956
TI  - Microwave-assisted solid-phase organic synthesis (MA-SPOS) of oxazolidinone
      antimicrobials.

PMID- 14722957
TI  - Automated synthesis of polysaccharides.

PMID- 14722958
TI  - Solid-phase oligosaccharide chemistry and its application to library synthesis.

PMID- 14722959
TI  - Design, synthesis, screening, and decoding of encoded one-bead one-compound
      peptidomimetic and small molecule combinatorial libraries.

PMID- 14722960
TI  - Intelligent design in combinatorial chemistry: use of designed peptide libraries
      to explore secondary and tertiary structures in peptides and proteins.

PMID- 14722961
TI  - Synthesis and screening of "one-bead one-compound" combinatorial peptide
      libraries.

PMID- 14722962
TI  - Synthetic combinatorial libraries as an alternative strategy for the development
      of novel treatments for infectious diseases.

PMID- 14722963
TI  - Advances in the applications of polymer-supported reagents for organic synthesis.

PMID- 14722964
TI  - Advanced polymer reagents based on activated reactants and reactive
      intermediates: powerful novel tools in diversity-oriented synthesis.

PMID- 14722965
TI  - Scavenger resins in solution-phase CombiChem.

PMID- 14722966
TI  - Cyclative cleavage strategies for the solid-phase synthesis of heterocycles and
      natural products.

PMID- 14722967
TI  - Derivatization reactions of heterocyclic scaffolds on solid phase: tools for the
      synthesis of drug-like molecule libraries.

PMID- 14722968
TI  - Library generation via postcondensation modifications of isocyanide-based
      multicomponent reactions.

PMID- 14722969
TI  - Mixture-based combinatorial libraries: from peptides and peptidomimetics to small
      molecule acyclic and heterocyclic compounds.

PMID- 14722970
TI  - New strategies for the solid-phase synthesis of highly functionalized, small
      molecules: sequential nucleophilic substitutions on polymer-bound
      polyelectrophiles.

PMID- 14722971
TI  - [SLA: a long way since Charcot].

PMID- 14722972
TI  - [Current trends in fibromyalgia].
AB  - Even if associating in single entity polyalgic symptoms remains a matter of
      discussion, fibromyalgia concept has gained a large acceptance among medical
      communities and international instances. Its physiopathological background is
      still in discussion. Its presentation mostly in middle aged women is a chronic,
      widespread painful syndrome, mostly appendicular of long duration and resistant
      to any treatment, associated with multiple tender points. Frequently associated
      are a poor sleep, local and general fatigue and mood disorders. Clinical,
      biological and radiological search for a definite condition remains negative, at
      least for primitive presentation. Concomitant forms are accepted by the American
      College of Rheumatology criteria, position which can be challenged. It seems more
      accurate to study such cases as differential diagnosis. Physiopathology involves
      anomalies of perception transmission and integration of painful signals at
      different levels of nervous system, either peripheral or central. Medical
      intervention requires first a good deal of empathy and a multidisciplinary
      approach combining some drugs, insufficient if used alone and different physical
      cognitive and comportemental measures. Fibromyalgia, which raises difficult
      social problems, is an evolving concept.

PMID- 14722973
TI  - [Endoscopic treatment of digestive neoplasia].

PMID- 14722974
TI  - [Medical complications of pregnancy: numerous factors].

PMID- 14722975
TI  - [Hypertension in pregnancy].
AB  - Hypertension is the most common medical complication of pregnancy. Isolated and
      moderate hypertensions most often have an uneventful course. On the contrary,
      preeclampsia is a severe condition, that threatens the fetal survival, and even
      maternal prognosis. Recent knowledge demonstrates that preeclampsia is related to
      a very early defect in placentation, with late maternal systemic effects. This
      has important practical counterparts. Any manifestation of placental dysfunction
      should be detected as early as possible. Antihypertensive treatment should be
      used with great caution, to preserve an appropriate blood flow through a placenta
      whose hemodynamic resistance is high. Finally, the most appropriate therapeutic
      way is a preventive one. Cardiovascular risk of those young women should be later
      monitored.

PMID- 14722976
TI  - [Hepatic complications of pregnancy].
AB  - Liver diseases specific of pregnancy, the most common hepatic complications of
      pregnancy, are always associated with a sometimes asymptomatic increase in serum
      aminotransferase activity. The most frequent of the liver diseases specific of
      pregnancy in normotensive pregnant women is cholestasis of pregnancy, the cause
      of generalised pruritus, and, in those with pregnancy-induced hypertension,
      preeclampsia which requires short-term cessation of pregnancy. Similar treatment
      is required by acute fatty liver of pregnancy the diagnosis of which must be done
      in the third trimester when recent polydipsia, nausea or vomiting occurs.
      Moreover, pregnancy increases the incidence and/or the severity of herpes simplex
      hepatitis (for which acyclovir therapy is urgently required) and hepatitis type
      E. Pregnancy may also unmask untreated cases of autoimmune hepatitis, Wilson's
      disease or Budd-Chiari syndrome.

PMID- 14722977
TI  - [Gestational diabetes].
AB  - Gestational diabetes represents 6% of all pregnancies and appears even in women
      without risk factors. This is in favour of a systematic screening between 24th
      and 28th weeks of gestation. There is as yet still no consensus concerning
      screening and diagnosis criteria but in France the guidelines are a two step
      approach: an O'Sullivan test > or = 7.15 mmol/L and a 100 g oral glucose
      tolerance test (OGTT). Gestational diabetes is defined by 2 or more abnormal
      values of the OGTT (Carpenter and Coustan criterias). Gestational diabetes has
      feto-maternal implications: on the one hand gravid hypertension and caesarean
      section, on the other hand macrosomia, respiratory distress and metabolic
      complications. The therapeutic management is first diet but insulin therapy is
      necessary in 40% of cases to obtain glycemic control. During the second part of
      pregnancy, to obtain a normoglycaemia can decrease and even normalise the rate of
      feto-maternal complications. Long-term management of women with gestational
      diabetes and treatment modalities also require better definition, since these
      patients are at risk for diabetes, mainly type 2. Diabetologists have to set
      prevention programs up.

PMID- 14722978
TI  - [Venous thromboembolism in pregnancy].
AB  - Venous thromboembolism has been reported to occur in 1 in 1,000 pregnancies, but
      is a leading cause of maternal mortality. The challenge is to identify women with
      risk factors for thromboembolism in pregnancy in order to initiate an appropriate
      treatment. The objective diagnosis of venous thromboembolism in pregnancy is
      crucial and have implications not only for management of the pregnancy but also
      for the choice of contraception and management of future pregnancies. Women with
      prior venous thrombosis, family history of thrombosis, or additional
      thrombophilic risks factors have to be evaluated in order to choice the best
      thromboprophylaxis for pregnancy and puerperium. However recommendations are of
      low grade (C) and in absence of large prospective studies, the therapeutic
      strategies are often empiric.

PMID- 14722979
TI  - [Recurrent miscarriage].
AB  - Repetitive spontaneous first trimester miscarriage as well as second and third
      trimester in utero fetal death are considered as recurrent pregnancy losses. They
      represent 1% of all pregnancies. Repetitive fetal loss with alive fetus should
      also be counted as such. An explanation is found for less than 50% of such
      patients. Most recurrent first trimester fetal losses are of chromosomal,
      hormonal, immunological, uterine or environmental origin. The most frequent
      causes for in utero fetal death are renovascular syndromes, hormonal or
      immunological pathologies, hereditary thrombophilias, red cell or platelet allo
      immunisation and chromosomal anomalies. Second trimester miscarriage is generally
      due to a cervical incompetence, uterine malformations or infections.

PMID- 14722980
TI  - [Psychological disorders in pregnancy].
AB  - If the high level of mental vulnerability marks the postpartum period, there are
      fewer mental diseases during pregnancy. Nevertheless, this period is marked by
      the importance of psychological change and the easier accessibility at
      psychotherapeutic interventions: then, unconscious conflicts can be approached as
      well as traumatic events. A lot of emotional and behavioral disorders remain
      within the norm. When the disorders are serious, they must be subjected to both
      therapeutic and preventive interventions to make sure the pregnancy goes as well
      as possible until birth and to help establish the mother-baby relationship. At
      the same time, these interventions are also a means of preventing postpartum
      disorders, in particularly postpartum depression. Specific disorders' such as
      denial of pregnancy (approximately 3 for 1,000) must be known, because there is a
      risk of infanticide. As for mental disorders already known, they involve
      cooperation between the maternity ward, physicians and the psychiatric department
      for the follow-up.

PMID- 14722981
TI  - [Teratogenesis and medication induced fetal toxicity].
AB  - The administration of pharmacological treatments during pregnancy always arouses
      concerns, shared both by the medical body and the general public. The drama of
      thalidomide, the main cause, has been followed by a number of efforts to develop
      some knowledge on the reality, nature and frequency of risk of malformation and
      foeto-toxicity, in particular from medications. A more rational approach to
      pharmacotherapy in the pregnant woman has come about following a position that
      was less supported and more alarmist. The principal idea that emerges consists of
      defending a more realistic evaluation of the risk:benefit ratio of
      pharmacotherapy in a sick pregnant woman, against the temptation of not treating
      or giving a maladaptive treatment. The second notion, essential in chronic
      pathologies, consists of supporting the efforts of multidisciplinary teams
      working in the pharmacotherapeutic management of pregnant women, to avoid errors
      of strategy that may be both medical and human.

PMID- 14722982
TI  - [Health at a glance by OECD].

PMID- 14722983
TI  - [Principal techniques of rehabilitation. Referral to physiotherapy and speech
      therapy. Part I: physiotherapy].

PMID- 14722984
TI  - [Sleep disorders in children and adults].

PMID- 14722985
TI  - [Intra-thoracic opacities and masses].

PMID- 14722986
TI  - [Chronic diarrhea].

PMID- 14722987
TI  - [The main ethical principles of the 20th century. II. From the Weimar Circular to
      the Huriet Law].

PMID- 14722989
TI  - Cutting cost without cutting benefits.

PMID- 14722988
TI  - In search of a gold standard.
AB  - This is a review article of relevant research to offer best-practice advice to
      the practitioner regarding the choice of intracoronal indirect restorative
      materials. The paper reviews the use of cast gold, a variety of porcelain
      materials and indirect composite resin materials as inlay materials. Subjects
      reviewed are the effects on tooth strength, the effect of bonding the material on
      tooth strength, stress analysis on teeth using different restorative material
      choice of luting material, wear of the material and its antagonist surface and
      clinical research outcomes and conclusions.

PMID- 14722990
TI  - What's a dentist to do?

PMID- 14722991
TI  - [Multimodal treatment of liver metastasis from colorectal carcinoma].

PMID- 14722992
TI  - [Surgery of rectal cancer in the third millennium].

PMID- 14722993
TI  - [Surgical treatment of malignant lip tumors. Personal experience].
AB  - The malignant tumours of the lip account for nearly 1-2% of the cervicofacial
      neoplasms. These lesions are frequently spinous cell carcinomas and basal cell
      carcinomas (25% of all oral cancers). The spinous cell carcinoma is mainly
      located in the lower lip, the basal cell carcinoma is more common in the upper
      lip. The incidence of lip cancer in males is much high than in females. The
      etiopathogenesis of these lesions is connected with exposure to sun, smoking,
      genetics predisposition (mutation of the p53 suppressor factor) and with the
      evolution of precancerous lesions (radiodermatitis, chronic cheilitis, xeroderma
      pigmentosum). Some Authors emphasized the viral etiopathogenesis: HPV16, HPV24,
      HSV1, HSV2. The treatment of lip carcinoma is surgical: excision and
      reconstruction. The numerous reconstructive techniques are mostly the cutaneous
      local sliding flaps and the rotation flaps. The lip reconstruction require a
      remarkable diligence for preserve, as much possible, the shape and functions of
      lip. The Authors report their experience about the surgical treatment of 19
      patients with lip carcinoma (16 spinous cell carcinomas, 3 basal cell carcinomas)
      and describe the main surgical reconstructive techniques to preserve the feeding,
      phonation and mimic expression.

PMID- 14722994
TI  - Mesenteric cystic lymphangioma causing intestinal occlusion in an adult patient.
AB  - Cystic lymphangioma is a benign tumor of uncertain etiology characterized by a
      slow growth; in 2-8% of cases it is localized in the mesentery. Symptomatology is
      aspecific and preoperative diagnosis is often difficult. The Authors report the
      case of a mesenteric cystic lymphangioma in a patient who had undergone subtotal
      colectomy eight years earlier for an adenocarcinoma occluding the sigmoid colon.
      The patient was hospitalized for intestinal occlusion.

PMID- 14722995
TI  - [Surgical treatment of lung metastasis: experience with 108 cases].
AB  - In this study the Author's analyze their experience (between September 1973 and
      December 2002) with 108 pulmonary resections for metastatic tumors to the lungs
      to evaluate prognostic factors and the impact on survival of extended
      metastasectomy. Overall mortality and major morbidity were 1.85% and 2.78%. The
      actuarial survivals at 5 and 10 years were respectively 46.6% and 39.9%. The best
      mean survivals are observed in patients with metastases from breast, colorectal,
      thyroid and urinary tract carcinomas, in cases with disease free interval > 12
      months and in the patients who underwent sequentially surgery and chemotherapy.
      Patients with pulmonary metastases also potentially benefit from iterative
      pulmonary resection.

PMID- 14722996
TI  - [Breath test as non-invasive assessment for the initial screening of non-ulcerous
      dyspepsia].
AB  - Considering the important role of Helicobacter Pylori (Hp) in the most common
      gastro-intestinal pathologies, the Authors want to test the effectiveness of a
      non-invasive diagnostic technique for detection of the Hp in the gastric mucosa.
      At the end of experience they think, like the most of Literature, that the Breath
      Test, concerning sensibility and specificity, represent the gold standard for
      detection of the Hp.

PMID- 14722998
TI  - [Arteriovenous brachio-basilic fistula as hemodialysis port. Original technique
      and long term results].
AB  - The authors report a prospective series of patients with-long term vascular
      access for chronic hemodialysis fashioned with a transposed brachio-basilic
      fistula. Over a three-year period (1998-2000), 14 patients underwent creation of
      the arteriovenous fistula. Demographic and clinical data were registered and a
      length of follow up more than 12 months was in all cases obtained. Of the 14
      fistulas performed, 7 were successfully used for dialysis without complication.
      In seven patients late revision of fistulas was performed. The primary and
      secondary patency actuarial rates at two years were 50% and 75% respectively. The
      results of this series highlight as the basilic vein fistula provides reliable
      vascular access for chronic hemodialysis therapy. The low cost and the low
      morbidity rates suggest the brachial artery-transposed basilic vein fistulas as a
      valuable part of vascular access history of patients with chronic renal failure.

PMID- 14722997
TI  - [MALT lymphoma of the gastrointestinal tract: description of clinical cases and
      review of the literature].
AB  - MALT-lymphomas are tumors of the mucosa associated lymphoid tissue, without
      primitive involvement of lympho nodes and spleen. They are located preferentially
      in the gastroenteric tract specially in the stomach (27%), but they may occur
      also in the respiratory and urinary tracts. There is a very well known link
      between MALT-omas and Hp infection, not only in the gastroenteric tract, but also
      in other sites. Moreover eradication of Helicobacter pylori can, in some cases,
      contribute to achieve the complete remission of the tumor. In this article the
      Authors report three cases of MALT-lymphomas: two of the stomach and one of the
      jejunum-ileum. Diagnosis is based on instrumental tests according to the involved
      tract and endoscopy of the upper digestive tract associated with biopsies more
      specific in case of gastric involvement; yet bioptic samples show a more
      significative incidence of false negative due to the extramucosal site of tumor.
      In these cases, a correct diagnosis will be obtained only through histologic
      examination of the surgical specimen. Surgery obtains good results in early
      stages, playing also a central role in palliation in association with radio- and
      chemotherapy. In case of low-grade B MALT-lymphomas of the stomach and in IE
      stages, eradication of Helicobacter pylori can, in 70-90% of cases, reduce the
      extension of the lymphocytic infiltration.

PMID- 14722999
TI  - [The use of Floseal in the prevention and treatment of intra- and post-operative
      hemorrhage in the surgical treatment of hemorrhoids and colporectocele.
      Preliminary results].
AB  - Stapled hemorrhoidectomy (PPH) is a modern approach to the treatment of
      hemorrhoids removing a circumferential strip of mucosa. In the same way the
      circumferential resection of the rectal prolapse (STARR) is successfully used for
      effective treatment of colporectocele and obstructed defecation syndrome. These
      surgical procedures offer several advantages over conventional techniques
      including reduced postoperative pain, stenosis and recurrences, an earlier
      recovery time and return to work. Furthermore, bleeding is one of the most common
      immediate complication (first week) and one of the possible late complication in
      these procedures. Our results with this surgery (153 PPH and 37 STARR) confirmed
      the data of many other Authors regarding the incidence of intra and early post
      operative haemorrhages (1.3% in PPH and 2.7% in STARR). With the aim to reduce
      this complications, which represents the only negative side-effect of these
      procedures, we employed the FloSeal, a gelatine based haemostatic sealant with
      thrombin component, to control intraoperative bleeding. The preliminary results
      obtained in 10 PPH and in 7 STARR confirmed the theoretical usefulness of FloSeal
      in reducing this hemorrhagic complications.

PMID- 14723000
TI  - [Telementoring in surgery].
AB  - Tele-mentoring is an interactive experimental method that allows young surgeons'
      education by distant learning tutoring of an expert surgeon. The problem about
      assessment of efficacy and quality of computer-assisted instruction is under
      evaluation today. Tele-mentoring is supported by videoconferencing system and it
      is not an exclusive methodology but an additional methodology to traditional
      didactic for clinicians and surgeons. It allows personal virtual trainings by
      computers and telecommunication systems. Videoconference allows tutoring for
      telemedicine, teletriage and telesurgery also.

PMID- 14723001
TI  - Evolving chemoradiation treatment strategies for locally advanced non-small-cell
      lung cancer.
AB  - Survival for patients with stage III non-small-cell lung cancer has gradually
      improved in recent years, with median survival times increasing from less than 10
      months to more than 18 months. These increases are thought to result primarily
      from advances in chemoradiation. This article reviews major advances in the
      development of chemoradiation for patients with locally advanced non-small-cell
      lung cancer. Results from cooperative group trials suggest that concurrent
      chemoradiation is superior to sequential therapy and may replace sequential
      therapy as the new standard of care in patients with good performance status.
      Technological advances such as 18F-fluorodeoxyglucose positron emission
      tomography (PET) staging can be used to improve patient selection and predict
      survival. Locoregional control may be improved by altering radiation
      fractionation or delivery (e.g., hyperfractionation, high-dose involved-volume
      radiotherapy, 3D conformal radiotherapy). Novel agents and regimens in
      combination with radiation are being investigated to further improve therapeutic
      outcomes.

PMID- 14723002
TI  - State-of-the-art treatment for advanced non-small-cell lung cancer.
AB  - Patients with locally advanced or metastatic non-small-cell lung cancer (stage
      III and IV) who are not candidates for surgery and exhibit good performance
      status are typically treated with concurrent radiation and platinum-based
      chemotherapy for disease palliation. Platinum-based chemotherapies, used alone or
      with radiation therapy, offer a small but significant survival benefit compared
      with supportive care. The incorporation of first-line agents such as gemcitabine
      (Gemzar), vinorelbine (Navelbine), and paclitaxel, as well as second-line agents
      such as docetaxel (Taxotere), in doublet and triplet combinations has had a
      further significant therapeutic impact. Randomized trials have shown that
      cisplatin-based therapy in combination with new agents results in improved 1- and
      2-year survival rates in patients with adequate performance status. The 1-year
      survival benefit has significantly improved, with greater symptom relief and
      improved quality of life in these patients. Thus, delaying disease progression
      with combination chemotherapy appears both beneficial and cost-effective in
      patients with advanced non-small-cell lung cancer. Newer approaches--including
      targeting critical signaling pathways, such as tyrosine kinase receptors,
      angiogenesis, and downstream signal transduction mechanisms--may provide novel
      agents with an improved toxicity profile and the potential for better disease
      management.

PMID- 14723003
TI  - Radiation sensitizers and targeted therapies.
AB  - Chemotherapeutic agents that are highly responsive to ionizing radiation and
      enhance the effectiveness of radiation treatment are termed radiation
      sensitizers. Radiation sensitizers act in a number of ways to make cancer cells
      more susceptible to death by radiation than surrounding normal cells, and several
      such compounds are now available for the treatment of solid tumors. This review
      discusses the biology that underlies chemotherapy and radiation interactions for
      one radiosensitizer--gemcitabine (Gemzar). It also provides a brief assessment of
      how to modify treatment regimens for various cancers to maximize the
      radiosensitization potential of gemcitabine in order to further increase
      efficacy. Newer molecularly targeted agents and their antitumor potential as
      monotherapy or in combination with radiation are also reviewed.

PMID- 14723004
TI  - Update on combined-modality treatment options for pancreatic cancer.
AB  - Cancer of the pancreas remains a formidable challenge in oncology. This
      malignancy ranks as the fourth leading cause of cancer death in the United States
      in 2003, with an estimated 30,700 new cases to be diagnosed and 30,000 deaths.
      Although gains have been achieved in the clinical management of these patients,
      this malignancy is rarely curable. Long-term survival is limited to patients
      undergoing resection. For patients with localized but unresectable malignancy,
      radiation therapy combined with fluorouracil, gemcitabine (Gemzar), or paclitaxel
      has shown modest improvements in survival and symptom palliation. However, there
      has been significant progress in the diagnostic evaluation of pancreatic cancer
      patients, which has aided clinicians in caring for these patients and in
      selecting therapies. The use of computed tomography, endoscopic ultrasonography,
      and laparoscopy techniques will be discussed. Newer techniques of radiation
      therapy, such as intraoperative electron-beam radiation therapy and three
      dimensional conformal radiation therapy, with the integration of new biologically
      targeted agents may provide new avenues of research and progress in this disease.

PMID- 14723005
TI  - OncoLink: old and gold.

PMID- 14723006
TI  - Current status of sentinel node surgery in breast cancer.
AB  - Sentinel node surgery potentially increases the accuracy of identifying lymph
      nodes that contain breast cancer and decreases morbidity compared to conventional
      axillary lymph node resection. However, no long-term comparisons of the two
      modalities have been carried out, and the survival benefit associated with one
      protocol vs the other remains unknown. Although sentinel node surgery is not
      expected to increase the cure rate of breast cancer patients, a significant
      reduction in the incidence of permanent side effects associated with axillary
      node resection will be a considerable advance. The completion of clinical trials
      establishing that no meaningful reduction in survival is associated with the
      decrease in side effects is important.

PMID- 14723007
TI  - Treatment strategies for myeloma bone disease.

PMID- 14723008
TI  - Comparing treatment outcomes using utility assessment for health-related quality
      of life.
AB  - When comparing treatments, the simple question of which treatment produces a
      better outcome prompts a complicated answer if both quantity and quality of life
      are considered. This is particularly evident when the treatment associated with
      better survival worsens quality of life, at least for part of the time, or when
      certain aspects of quality of life are better with one treatment while other
      aspects are better with another treatment. Utility assessment is an evolving
      discipline that offers an attractive conceptual solution to these problems. The
      popular approaches are described, and one particular method, the standard gamble,
      is advocated. Utility is easily measured by the standard gamble, and it has good
      psychometric and theoretical properties.

PMID- 14723009
TI  - Study finds minimally invasive esophagectomy improves survival, shortens hospital
      stays.

PMID- 14723010
TI  - Clinical trials referral resource. Current clinical trials investigating cancer
      in the elderly.

PMID- 14723011
TI  - Docetaxel regimen provides survival benefits in advanced stomach cancer patients.

PMID- 14723012
TI  - Hematopoietic management in oncology practice. Part 2. Erythropoietic factors.
AB  - As the major regulator of erythropoiesis in man, erythropoietin inhibits the
      programmed cell death of committed erythroid precursors. In cancer patients, a
      relative erythropoietin deficiency is coupled with a decreased responsiveness to
      the substance mediated by the effects of inflammatory cytokines on the marrow and
      on ferrokinetics, leading to a high incidence of anemia. Two recombinant human
      erythropoietin (rhEPO) preparations--epoetin alfa (Epogen, Procrit) and epoetin
      beta (Marogen)--as well as a modified erythropoietic compound (darbepoetin alfa
      [Aranesp]) are in clinical use. Part 2 of this two-part series on hematopoietic
      agents reviews the use of these erythropoietic factors and their effect on the
      anemia that develops in cancer patients. Thrombopoietic factors and progenitor
      cell-mobilizing factors are also briefly addressed.

PMID- 14723013
TI  - DNA microarrays in lymphoid malignancies.
AB  - Gene expression profiling using cDNA microarrays has the potential to improve
      current lymphoma classification schemes by establishing a molecular diagnosis of
      these malignancies. The use of this technology led to the discovery of
      biologically and clinically distinct subtypes of diffuse large B-cell lymphoma
      (DLBCL). Gene expression data can also be used to formulate powerful mathematical
      algorithms that predict the clinical outcome in patients with DLBCL and mantle
      cell lymphoma. In B-cell chronic lymphocytic leukemia, gene expression profiling
      identified ZAP70, an important prognostic marker whose expression correlates with
      the mutational status of the immunoglobulin heavy chain gene and, therefore, with
      survival in these patients. These examples illustrate that gene expression
      profiling may pave the way for detailed molecular characterization of lymphoid
      malignancies that will ultimately lead to tailored, disease-specific therapies.

PMID- 14723014
TI  - Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and
      management.
AB  - Oropharyngeal mucositis is a common and treatment-limiting side effect of cancer
      therapy. Severe oral mucositis can lead to the need to interrupt or discontinue
      cancer therapy and thus may have an impact on cure of the primary disease.
      Mucositis may also increase the risk of local and systemic infection and
      significantly affects quality of life and cost of care. Current care of patients
      with mucositis is essentially palliative and includes appropriate oral hygiene,
      nonirritating diet and oral care products, topical palliative mouth rinses,
      topical anesthetics, and opioid analgesics. Systemic analgesics are the mainstay
      of pain management. Topical approaches to pain management are under
      investigation. The literature supports use of benzydamine for prophylaxis of
      mucositis caused by conventional fractionationated head and neck radiotherapy,
      and cryotherapy for short-half-life stomatoxic chemotherapy, such as bolus
      fluorouracil. Continuing studies are investigating the potential use of biologic
      response modifiers and growth factors, including topical and systemic delivery of
      epithelial growth factors and agents. Progress in the prevention and management
      of mucositis will improve quality of life, reduce cost of care, and facilitate
      completion of more intensive cancer chemotherapy and radiotherapy protocols. In
      addition, improved management of mucositis may allow implementation of cancer
      treatment protocols that are currently excessively mucotoxic but may produce
      higher cure rates. Continuing research related to the pathogenesis and management
      of mucositis will undoubtedly lead to the development of potential interventions
      and improved patient care.

PMID- 14723015
TI  - CT-2103 extends median survival of high-risk lung cancer patients.

PMID- 14723016
TI  - [Hematocrit as an indicator for coronary intervention in patients with acute
      myocardial infarction].
AB  - OBJECTIVES: Primary coronary intervention in patients with acute myocardial
      infarction complicated by persistent massive intracoronary thrombus is frequently
      difficult. Higher incidence of thrombus formation is associated with high
      hematocrit score. This study investigated the relationship between high
      hematocrit score and primary coronary intervention in patients with acute
      myocardial infarction. METHODS: Forty-five patients with acute myocardial
      infarction were divided into two groups according to hematocrit score on
      admission, the high hematocrit group (hematocrit > or = 48%, n = 8) and the low
      hematocrit group (hematocrit < 48%, n = 37). Time period required for coronary
      intervention (intervention time), number of balloon inflations, presence of
      persistent massive intracoronary thrombus, need for adjunctive intracoronary
      thrombolysis, need for intraaortic balloon pumping and achieved rate of
      Thrombolysis in Myocardial Infarction (TIMI) 3 were compared between the two
      groups. The relationships between hematocrit and intervention time or number of
      balloon inflations were also investigated. RESULTS: Intervention time (2.7 +/-
      1.4 vs 1.4 +/- 0.7 hr, p = 0.0003), number of balloon inflations (12 +/- 9 vs 3
      +/- 2 times, p = 0.0001), presence of persistent massive intracoronary thrombus
      (100% vs 5%, p < 0.0001), intracoronary thrombolysis (63% vs 3%, p = 0.0003), and
      intraaortic balloon pumping (63% vs 14%, p = 0.0092) were significantly higher in
      the high hematocrit group. However, the rate of TIMI 3 (25% vs 95%, p < 0.0001)
      was significantly lower in the high hematocrit group. The relationships between
      hematocrit and intervention time (r2 = 0.16, p = 0.0033), and hematocrit and
      number of balloon inflations (r2 = 0.19, p = 0.0015) showed positive
      correlations. CONCLUSIONS: Primary coronary intervention for patients with acute
      myocardial infarction showing high hematocrit score on admission is likely to be
      difficult due to the presence of persistent massive intracoronary thrombus.
      Therefore, coronary interventional strategy for intracoronary thrombolysis in
      patients with acute myocardial infarction should include measurement of
      hematocrit score.

PMID- 14723017
TI  - [Three-dimensional analysis of left ventricular geometry using magnetic resonance
      imaging: feasibility and comparison with echocardiographic analysis].
AB  - OBJECTIVES: Reliability of left ventricular geometry assessed by echocardiography
      (Echo) using an assumed left ventricular mass (LVM) and one-dimensional
      eccentricity (relative wall thickness: RWT), remains questionable. This study
      evaluated the feasibility of three-dimensional left ventricular geometric
      analysis using magnetic resonance imaging (MRI). METHODS: Echocardiography and
      MRI were performed on 55 patients with hypertension. LVM was calculated using 0.8
      (American Society of Echocardiography-cube LVM) + 0.6 g for Echo and the slice
      summation method for MRI. Eccentricity was determined by RWT (septal wall
      thickness + posterior wall thickness/left ventricular inner diameter) for Echo
      and LVM/1.05/left ventricular end-diastolic volume (LVEDV) ratio [MRI-mass
      volume/cavity (M/C) ratio] for MRI. Left ventricular geometry was classified into
      four patterns according to the presence/absence of left ventricular hypertrophy
      and abnormal/normal eccentricity (partition value: RWT = 0.44, MRI; M/C ratio =
      2.0), and the patient distribution was compared between the two methods. RESULTS:
      Although the mean values for LVM were similar, the mean value for LVEDV by
      echocardiography was significantly higher (p < 0.0001) and the mean M/C ratio was
      significantly lower (r = 0.004) than those by MRI. There were widely dispersed
      LVM values at higher underlying values of LVM and significant correlations
      between MRI-LVEDV and MRI-LVM (r = 0.87) and between Echo-LVEDV and Echo-LVM (r =
      0.75). There was a significant difference in patient distribution according to
      left ventricular geometric pattern between the two methods (p < 0.01). Concentric
      (n = 18) and eccentric hypertrophy (n = 12) were dominant patterns in Echo
      analysis, and concentric hypertrophy (n = 23) and concentric remodeling (n = 21)
      were dominant in MRI analysis. The left ventricular geometric patterns were
      different in 32 patients (58.0%). Inadequate LVEDV values in Echo were the
      primary cause of this phenomenon. CONCLUSIONS: Left ventricular geometric
      analysis by Echo results in inaccurate values. Three-dimensional left ventricular
      geometric analysis using MRI provides more accurate information about left
      ventricular geometry.

PMID- 14723018
TI  - [Current practice in low-density lipoprotein-cholesterol measurements for the
      clinical management of hyperlipidemia].
AB  - OBJECTIVES AND METHODS: Low-density lipoprotein cholesterol (LDL-C) measurements
      in clinics were evaluated by a multiple-choice questionnaire sent to 146
      physicians (78 general practitioners and 68 hospital physicians) in Niigata
      Prefecture, Japan. RESULTS: Seventy-six percent of the general practitioners and
      84% of the hospital staff measured LDL-C, and 60% of all physicians calculated
      LDL-C using the Friedewald formula. Sixty-two percent of general practitioners
      and 43% of hospital physicians took blood samples without overnight fasting and
      40-50% of whom estimated LDL-C using the Friedewald formula, although the formula
      is reliable only for samples collected after an overnight fast. Two thirds of the
      physicians managed patients according to the Japan Atherosclerosis Society
      Guidelines (1997), whereas 40-50% based diagnoses and treatments on total
      cholesterol, and only 20-30% used LDL-C-based management. CONCLUSIONS: Direct
      measurement, education and management of LDL-C not affected by diet are
      mandatory.

PMID- 14723019
TI  - Rhythm-independent feature of heart rate dynamics common to atrial fibrillation
      and sinus rhythm in patients with paroxysmal atrial fibrillation.
AB  - OBJECTIVES: To examine if the long-range correlation in heart rate variability is
      a rhythm-independent characteristic common to both atrial fibrillation (AF) and
      sinus rhythm (SR) periods in patients with paroxysmal atrial fibrillation (PAF).
      METHODS: Holter electrocardiography was analyzed during sleep in 18 patients with
      paroxysmal atrial fibrillation during the atrial fibrillation (PAF-AF) and sinus
      rhythm (PAF-SR) periods, and also in 19 healthy controls with sinus rhythm (CTR
      SR). The heart rate dynamics were assessed with the power-law spectral exponent
      (slope) of the log-log power spectrum between 0.0001 Hz and the breakpoint
      frequency. RESULTS: The slope showed a significant correlation between PAF-SR and
      PAF-AF (r = 0.614, p < 0.01). During sinus rhythm, the slope in paroxysmal atrial
      fibrillation with cardiovascular disease [PAF-SR (cvd+)] was steeper than that in
      paroxysmal atrial fibrillation without cardiovascular disease [PAF-SR (cvd-)] (p
      < 0.05). Although the slope was comparable between PAF-SR (cvd-) and CTR-SR, the
      slope in PAF-SR (cvd+) was steeper than that in CTR-SR (p < 0.05). A similar
      tendency was shown during atrial fibrillation. The slope in paroxysmal atrial
      fibrillation with cardiovascular disease [PAF-AF (cvd+)] was steeper than that in
      paroxysmal atrial fibrillation without cardiovascular disease [PAF-AF (cvd-)] (p
      < 0.05). Although the slope was comparable between PAF-AF (cvd-) and CTR-SR, the
      slope in PAF-AF (cvd+) tended to be steeper than that in CTR-SR. CONCLUSIONS: The
      long-range correlation in heart rate variability during sleep was a rhythm
      independent characteristic and so may have a similar clinical value during atrial
      fibrillation and sinus rhythm in patients with paroxysmal atrial fibrillation.

PMID- 14723020
TI  - [Intravascular ultrasound guided polytetrafluoroethylene coronary stent graft
      implantation in a patient with a large coronary pseudoaneurysm at eight months
      after coronary intervention: a case report].
AB  - A 67-year-old man with exertional angina presented with a large pseudoaneurysm of
      the right coronary artery at eight months after balloon angioplasty.
      Intravascular ultrasound revealed a large saccular pseudoaneurysm of 10.9 x 5.7
      mm diameter at the proximal segment of the right coronary artery. Complete
      closure of the coronary pseudoaneurysm was successfully obtained using a coronary
      stent graft consisting of a thin flexible polytetrafluoroethylene (PTFE) membrane
      placed between two stents using a unique sandwich technique. Follow-up
      angiography and intravascular ultrasound revealed no significant restenosis in
      the PTFE stent graft segment. PTFE coronary stent graft implantation is a
      feasible, safe and useful method to treat a large coronary pseudoaneurysm after
      coronary intervention.

PMID- 14723021
TI  - [A 85-year-old man complaining of lumbago and back pain after recovery from
      pneumonia and paralytic ileus].

PMID- 14723022
TI  - [The importance of a complete diagnostic workup in patients with nontraumatic
      (partial) paraplegia].
AB  - In two women, aged 86 and 56 years, respectively, who suffered from back pain and
      loss of strength, and in a 55-year-old man who lost sensation and strength in his
      left leg, spinal-cord compression in connection with vertebral destruction was
      seen on radiological examination. When spinal-cord compression is the result of a
      local malignant tumour, the therapy often entails emergency radiotherapy. In the
      first two patients, histological examination revealed a solitary plasmocytoma and
      curative high-dose radiotherapy was applied. The third patient also had a lung
      tumour and received low-dose palliative radiotherapy to the vertebrae, as a
      metastasis was suspected. Later, however, histopathologic examination of the
      vertebral lesion revealed osteomyelitis due to Listeria monocytogenes and the
      lung tumour was diagnosed as a pT2N0M0 broncho-alveolar carcinoma which was
      surgically removed. When a patient is referred with a nontraumatic spinal-cord
      injury, it is important to complete the radiological and histological
      examinations before starting emergency radiotherapy in order to prevent an
      inadequate or even incorrect treatment.

PMID- 14723023
TI  - [The Nobel Prize in Chemistry 2003 awarded for discoveries concerning molecular
      channels in cell membranes].
AB  - About 70% of the human body consists of salt water. The Nobel Prize 2003 in
      Chemistry rewards Peter Agre for the discovery of water channels and Roderick
      MacKinnon for structural and mechanistic studies of ion channels. Their studies
      have demonstrated how ions and water are transported through cell membranes. This
      transport is essential for the regulation of size and osmotic pressure in cells
      and organelles and it plays a major role in salt and water homoeostasis and in
      the generation of electrical signals in nerve cells. Agre succeeded in isolating
      a membrane protein which later studies revealed to be a long-postulated water
      channel, MacKinnon succeeded in determining the spatial structure of a potassium
      channel.

PMID- 14723024
TI  - [The practice of systematic reviews. XI. The Cochrane Library].
AB  - Systematic reviews of the literature provide a summary of the current status of
      medical scientific research. They are important for the solution of medical
      questions by doctors active in clinical practice, may serve to support practice
      guidelines, and are used in health care to take policy decisions and to determine
      the research agenda. The Cochrane Library is the most important source of
      information on the efficacy of interventions in health care and comprises eight
      databases. The most relevant for doctors active in clinical practice are the
      Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of
      Effects, and the Cochrane Central Register of Controlled Trials. At present, the
      first two databases contain over 5000 systematic reviews of the literature. The
      third database listed above is the largest database in the world with references
      to (randomised) controlled studies.

PMID- 14723025
TI  - [DNA damage and aging].
AB  - At present the mouse is the ideal experimental animal for studying molecular
      biological processes in human diseases. Premature aging occurred in mice with an
      induced mutation that resulted in a defective DNA repair mechanism. Compared to
      normal unmanipulated mice they exhibited characteristic symptoms of premature
      aging, such as premature greying, aging of the skin, osteoporosis, kyphosis,
      early menopause and a reduced longevity. Although these experiments only cover a
      small number of the many aging symptoms present in humans, it is nevertheless
      clear that DNA damaged by free oxygen radicals but which is not repaired, is an
      important cause of the onset of aging.

PMID- 14723026
TI  - [Diagnostic image (170). A woman with papules in the axillae. Reactive,
      perifollicular fibrosis].
AB  - A 36-year-old woman presented with persistent skin-coloured papules in the
      axillae after waxing, caused by reactive perifollicular fibrosis.

PMID- 14723027
TI  - [Obstructive azoospermia in men who wish to father children; diagnosis and
      surgical sperm retrieval].
AB  - OBJECTIVE: To evaluate diagnostic procedures and surgical sperm retrieval in men
      with suspected obstructive azoospermia who wish to father children. DESIGN:
      Descriptive, retrospective. METHOD: During the period 1 April 1999-31 December
      2001 93 men suspected of having obstructive azoospermia underwent surgical sperm
      retrieval by means of percutaneous epididymal sperm aspiration (PESA). In each
      patient a testicular biopsy was performed to determine the Johnsen score (a score
      > or = 8 is equivalent to a normal spermatogenesis). Cryopreservation was
      performed whenever possible. The findings in both percutaneous and surgical sperm
      retrieval were compared. RESULTS: In 76 patients (82%) epididymal motile sperm
      were obtained using PESA. Their Johnsen score on the testis biopsy was 9.1
      (range: 7.4-10). In 73 of the patients the Johnsen score was > or = 8. In the 17
      patients (18%) in whom no sperm were found with PESA, the median Johnsen score
      was 5.8 (range: 2-9.8). Epididymal sperm were not found in patients with a
      testicular volume < 15 ml. In all 28 patients who had undergone a vasectomy in
      the past, motile sperm were found along with a Johnsen score > or = 8. In 23 of
      the 24 patients with congenital bilateral absence of the vas deferens (CABVD) the
      Johnsen score was > or = 8. Cryopreservation was possible in 45 (59%) of all
      patients and in 5 (35%) of the 13 patients with an unknown cause for the
      obstructive azoospermia. CONCLUSION: In men with suspected obstructive
      azoospermia in whom sperm were found using PESA, a diagnostic testis biopsy
      provided no additional relevant information about the spermatogenesis. There was
      always a good spermatogenesis after vasectomy. CBAVD patients probably had at
      least some focal areas in the testes with normal spermatogenesis. Sperm retrieval
      and cryopreservation could be carried out less frequently in the case of
      obstructions with an unknown cause.

PMID- 14723028
TI  - [Obstructive azoospermia in men who wish to father children; initial clinical
      results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved
      epididymal semen].
AB  - OBJECTIVE: To evaluate the results of intracytoplasmatic sperm injection (ICSI)
      with surgically retrieved epididymal semen. DESIGN: Prospective, descriptive.
      METHODS: Patients with an obstructive azoospermia confirmed by cytological
      examination of a testis biopsy, and conforming to the regular IVF/ICSI criteria
      as laid down in 2001 at the University Medical Centre St Radboud Nijmegen, the
      Netherlands, were included for percutaneous epididymal sperm aspiration (PESA)
      and ICSI. The main outcome measure was the ongoing pregnancy rate per initiated
      cycle. RESULTS: A total of 44 cycles were started in 31 couples. In 43 cases
      (98%) an ovum pick-up was performed and 41 (93%) embryo transfers were carried
      out. In 19 (43%) cases, treatment resulted in a positive pregnancy test and 15
      (34%) ongoing pregnancies were recorded. In total, 17 healthy children were born
      (11 boys and 6 girls). CONCLUSION: ICSI with surgically retrieved semen was
      successfully used as a treatment for childlessness caused by obstructive
      azoospermia.

PMID- 14723029
TI  - [Post mortem semen acquisition: not without 'informed consent'].
AB  - Recently, two requests for post-mortem semen acquisition were evaluated and
      rejected. The first request was from the wife of a man who died after the wedding
      night. In the second case, the wife requested that electroejaculation be done on
      a man who was brain dead because of a gunshot wound in the head. In both cases,
      the fact that there was no written consent from the men involved before they died
      was the deciding reason not to grant the requests. Written consent is legally and
      ethically seen as the final episode of a period in which persons have considered
      the consequences of the acquisition, storage and use of semen after the death of
      the husband.

PMID- 14723030
TI  - [Surgical decompression in space-occupying cerebral infarct; notification of a
      randomized trial].
AB  - Patients with a hemispheric infarct and massive space-occupying brain oedema have
      a poor prognosis. Despite intensive conservative treatment, the case fatality
      rate may be as high as 80%, and most survivors are left severely disabled. Non
      randomised studies suggest that decompressive surgery substantially reduces
      mortality and improves the functional outcome of survivors. The 'Hemicraniectomy
      after middle cerebral artery infarction with life-threatening edema trial'
      (HAMLET) is a newly-conceived randomised multi-centre clinical trial that
      compares the efficacy of decompressive surgery to improve functional outcome with
      that of conservative treatment in patients with space-occupying supratentorial
      infarction.

PMID- 14723031
TI  - [Hemopyrrollactamuria (HPU); from spots to pseudo-disease].

PMID- 14723032
TI  - [Hemopyrrollactamuria (HPU); from spots to pseudo-disease].

PMID- 14723033
TI  - [Medical-scientific societies, quality control and disfunctional physicians].

PMID- 14723034
TI  - [Medical-scientific societies, quality control and disfunctional physicians].

PMID- 14723035
TI  - [Medical-scientific societies, quality control and disfunctional physicians].

PMID- 14723036
TI  - [Medical-scientific societies, quality control and disfunctional physicians].

PMID- 14723037
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723038
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723039
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723040
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723041
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723042
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723043
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723044
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723045
TI  - [Diseases and the diseased--scientific and alternative medicine].

PMID- 14723046
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2003 current population survey.

PMID- 14723047
TI  - [Effects of Cisplatin on Auditory Function in Children with cancer. Otoacoustic
      Emission Evaluation].
AB  - This study was done to ascertain prospectively whether distortion product-evoked
      otoacoustic emissions (DP-EOAE) might detect changes in specific frequencies
      damaged in inner ear function earlier, before they become permanent after
      cisplatinum exposure for cancer treatment in children. Sixteen children treated
      with cisplatinum for various types of cancer were repeatedly evaluated after each
      chemotherapy session; results were compared to 44 controls. We observed a
      progressive damage in auditory function. In second assessment 50% of DP-EOAE
      studies were abnormal; in the third study, 66% were abnormal, and in the fourth
      test 71% were abnormal. Our results suggest that DP-EOAE are useful tests for
      earlier auditory changes induced by cisplatinum therapy; higher frequencies are
      the most affected, and we propose that DP-EOAE be a mandatory test before
      treatment and during cisplatinum therapy to detect or diagnose early hearing
      loss.

PMID- 14723048
TI  - [Cerebral Blood flow velocity spectrum by transcranial doppler ultrasound in
      patients with brain death clinical criteria].
AB  - OBJECTIVE: To evaluate cerebral blood flow (CBF) direction, speed, and shape of
      Doppler profile in patients with clinical criteria of brain death (BD). PATIENTS:
      A total of 42 consecutive patients with clinical criteria for BD were included.
      MEASUREMENTS AND INTERVENTIONS: After anemia, hypothermia and hypocapnia were
      ruled out; confirmatory electroencephalogram (EEG) and a complete transcranial
      Doppler ultrasonography (TCDU) profile of circle of Willis and basilar arteries
      were done in all patients. Patients continued with mechanical ventilation and
      support in the Intensive Care Unit. RESULTS: All EEG reported generalized theta
      and delta waves, which were associated with a TCDU profile showing small systolic
      peaks without diastolic wave. CBF velocities of < 10 cm/sec were recorded in all
      patients. Only four patients had reverberating flow. At follow-up, cardiac arrest
      occurred in all patients at a mean of 2 +/- 0.84 days. CONCLUSIONS: Patients with
      clinical criteria of BD frequently have slow wave neuronal electrical activity on
      EEG that anticipates cardiac arrest. In these patients, TCDU detects an early and
      severe drop in CFB that is incompatible with life. TCDU should be done when other
      confirmatory tests like EEG suggest some retention of brain function.

PMID- 14723049
TI  - [Description of chagas disease in the Valle de Iguala, Guerrero state, Mexico-
      Marco].
AB  - There are reports regarding the presence of triatomine vectors of Trypanosoma
      cruzi, the causal agent of Chagas' disease, and infected individuals on the coast
      and zones south of the State of Guerrero, Mexico. Nonetheless, there are no
      completed reports in the Valley of Iguala. To know with greater precision endemic
      zones, seropositive individuals and their health condition, T. cruzi-infected
      triatomines and characteristics of dwellings were studied. Seroprevalence was
      1.8% by indirect ELISA and latex agglutination techniques were carried out in
      serum of 450 individuals of three municipalities of the Valley of Iguala. We
      reported presence of triatomine and conditions of dwellings. Of 71 triatomines
      collected, 38.2% were infected with T. cruzi. Triatoma pallidipennis was the only
      triatomine species found. No seropositive persons presented intestinal, or
      cardiac problems. The greatest percentage of infected triatomines was observed in
      rural zones as compared to urban. Results suggest considerable risk of infection
      in the Valley of Iguala but studies regarding the infectivity capacity of T.
      cruzi strains are required.

PMID- 14723050
TI  - [Why is surgery cancelled? causes, implications, and bibliographic antecedents].
AB  - OBJECTIVE: To identify the causes of cancellation of scheduled surgical
      procedures at a General Hospital and review of the literature. PROCEEDINGS: The
      record of scheduled surgery was reviewed at 1 year. We identified frequency of
      cancellation and the three main sources including hospital, medical team, and
      patient. RESULTS: Scheduled surgery record registered 3,627 surgical procedures;
      863 were cancelled. The last 4 months of the year registered the majority of
      cases. Nearly 60% of suspensions were in Orthopedics (26.6%), General Surgery
      (22.13%), Gynecology (17.84%), and Ophthalmology (10.06%). Forty percent of total
      cancelled surgery was related with patient causes, 30% to hospital sources, and
      29.8% to deficiencies of the medical team. CONCLUSION: Rate of scheduled surgery
      cancellation was 23.79%. It was most important during the last 4 months of the
      year. Orthopedics, General Surgery, Gynecology, and Ophthalmology were the main
      specialties involved. Sources of cancellation were identified as patient causes,
      in first place; hospital deficiencies and medical team reasons shared the second
      place. Situational diagnosis of each hospital and a presurgical assessment clinic
      reduce rate of cancelled surgical procedures.

PMID- 14723052
TI  - [Retroperitoneal hematoma in children].
AB  - INTRODUCTION: Retroperitoneal hematoma is frequently due lo blunt trauma and is a
      challenging problem. Incidence of this complication in adults is high, but in
      childhood is uncommon. MATERIALS AND METHODS: Analysis of 30 cases is presented.
      PTS was found between 10 and 12 points, zone II, 12, zone III, 17, and zone I,
      only one. We observed 33 associated injuries: 17 were pelvic fractures and nine,
      ureteral rupture. Three patients underwent hepatic or splenic laceration. Seventy
      three percent of patients had exploratory laparotomy, but did not have
      exploration of retroperitoneum. CONCLUSIONS: Retroperitoneal hematoma in infancy
      should be treated conservatively.

PMID- 14723051
TI  - [Analysis of Bcr-abl type transcript and its relationship with platelet count in
      Mexican patients with chronic myeloid leukemia].
AB  - PROBLEM: It has been suggested that type of chimeric mRNA is associated with
      differences in the clinical and hematologic characteristics of chronic myeloid
      leukemia (CML). However, prognostic value of type of chimeric mRNA bcr-xabl (b3a2
      or b2a2) is still controversial. METHODS: We analyzed 97 cases of Philadelphia
      positive CML to determine mRNA type by reverse-polymerase chain reaction (RT-PCR)
      and its relationship with clinical features. RESULTS: We detected b3a2 bcr-abl
      transcripts in 27 (28%) cases, b2a2 in 57 (59%) cases, and 13 (13%) with both
      mRNA transcripts b3a2/b2a2. These frequencies were the total reverse of other
      reports. Age, sex, hemoglobin, and white-cell counts showed no significant
      difference for those with either b3a2 or b2a2 bcr-abl transcripts. However,
      platelet counts of b3a2 patients were significantly higher than those of b2a2
      patients (743.3 vs 477.3 x 109/L; p = 0.01). In addition, in the subgroup of
      patients whose white-cell count at diagnosis was < 100 x 10(9)/L, those with b3a2
      transcript had a significantly higher platelet count (679.1 vs. 352.2 x 10(9)/L;
      p = 0.001). CONCLUSIONS: We observed reversed frequency of bcr-abl transcripts in
      this population, but agreement with other Latin-American reports. In addition,
      our data suggested that there is different CML biological behavior in our
      population and that there is a subpopulation of CML patients in whom b3a2 is
      associated witH higher thrombopoietic activity.

PMID- 14723053
TI  - [Radiosurgery: a new form of bloodless surgery].

PMID- 14723054
TI  - [The clinical importance of insulin-like growth factors].
AB  - OBJECTIVE: To review the physiologic role of IGFs and impact in the clinical
      area. MATERIALS: We carried out a search in MEDLINE and INDEX MEDICUS from 1995
      to 2000 and relevant articles were selected. RESULTS: IGFs are polypeptides
      involved in cellular development and growth. Their structure is similar to
      proinsulin. The biological effects of IGFs are produced when they bind their
      receptors. The majority of circulating IGFs are bound to specific proteins called
      IGFBPs that modulate the effects of IGFs. Imbalance in IGF-IGFBP production is
      associated with several pathological conditions. CONCLUSIONS: Several studies
      have demonstrated that administration of IGFs may be a promissory treatment for
      certain diseases related not only to growth, but also to diabetes mellitus,
      hyperinsulinism, and some cardiopathies.

PMID- 14723055
TI  - [Twenty- Year old male with endocranial hypertension].

PMID- 14723056
TI  - [Amniotic fluid embolism direct cause of maternal death. Clinical case report].
AB  - Embolic complications in pregnancy are not common, but require prompt attention
      due to their high mortality, with reports of numbers up to 80% in patients with
      presence of amniotic fluid embolism. Of the embolic complications, deep vein
      thrombosis is the most frequent and 15-24% of patients could present with
      amniotic fluid embolism. In the case of a 42-year-old female who had this
      syndrome, it was considered an obstetric catastrophe. A review of the world
      literature was carried out to report on the physiopathology of the case.

PMID- 14723057
TI  - [Extraovarian sex cord mesenchymatose tumor].
AB  - A 32-year-old female presented with a large tumoral mass in the left upper
      quadrant (ULQ) of the abdomen with abdominal and retroperitoneal components,
      infiltrating the spleen and adhered to pancreatic tail, colon, left kidney, and
      stomach that could be completely resected along with the spleen. Histopathologic
      study including immunohistochemical profile was coincident with results obtained
      at Barnes-Jewish Hospital of Washington University Medical Center, USA. This
      study showed areas of granulosa tumor cells as well as thecal features of
      fusiform cells with eosinophilic cytoplasm and tubular formations corresponding
      to Sertoli cells. According with embryologic development, the specialized stroma
      of the genital crest is induced to proliferase after primordial germ cells
      infiltrate the crest; in this way, tumoral growth can occur at any site along
      this migration. The predominating localization of this unique ectopic tumor
      coincides with the descending route of the ovaries or its components. This case,
      included in unclassified forms of stromal sex cord tumors, is considered a
      monodermal malignant teratoma. Is was the second tumor of retroperitoneal
      localization and the eleventh ectopic, according to the world literature
      reviewed.

PMID- 14723058
TI  - [Sanitary control of communicable diseases in Hispanic America in the XVI, XVII,
      and XVIII centuries].
AB  - In each time and each place, man has avoided diseases, has tried to limit
      diffusion of diseases. The purpose of this article was to present in a general
      manure the measures taken in Hispano America during colonial times to control
      communicable diseases. The main problems of health during the XVI, XVII, and
      XVIII centuries, in Hispano American region were communicable diseases. Practices
      to avoid them derived from observation, control measures referred to stay away
      from the contagious places, and to isolate sick persons by means of quarantine,
      and implied some epidemiologic surveillance. The supply of safe drinking water,
      sewage disposal systems and sanitary control of food were not habitual practices;
      garbage, residuals, and waste collection were not opportune, This favored the
      existence of vectors-insects and animals. Domestic waste did not go away in a
      timely fashion, it allowed to accumulate excreta and waste near houses. In some
      places, the were measures related to water supply, excreta disposal, handling of
      dead bodies, and environmental sanitation. It was believed that with prayers and
      processions, prevalent diseases could be avoided. Demographic information, data
      on mortality, births, and morbidity, were irregular and incompletes, some data
      were compiled in parishes: physicians should inform and notify the governmental
      medical board, which regulated medicine and public heath who the cared for an
      action carried out only as and exception. Compiled data had no clear medical or
      sanitary use.

PMID- 14723059
TI  - [Type 2 neurofibromatosis].

PMID- 14723060
TI  - [The metabolic syndrome in postmenopausal women. Clinical implications].
AB  - Cardiovascular diseases (CVD) remain the major cause of death in postmenopausal
      women. Before menopause, women are relatively protected from ischemic heart
      disease and thromboembolism by their circulating estrogens, but this protection
      is lost after menopause. Following menopause, adverse lipid changes occur and the
      levels of several coagulation factor increase. One of the major predisposing
      factors for CVD is the metabolic syndrome, including myriad risk biomarkers:
      abdominal girth, blood pressure, fasting glucose, triglycerides, lipids. In many
      ways, the metabolic syndrome is a precursor to the development of abnormalities
      of insulin action and diabetes. In parallel, there are effects upon blood
      coagulation and fibrinolysis. Common preventive therapies require rigorous
      evaluation. Hormone replacement therapy (HRT) has not produced the expected
      reduction in CVD and the ideal HRT is probably unobtainable. For long-term HRT
      users, the risk of thromboembolism needs to be weighed against probable benefits.
      With respect to the effects of HRT, oral estrogen is associated with elevation in
      C-reactive protein and varied effects on IL-6, but transdermal estradiol has no
      significant effect on these parameters. Despite the varied effects of HRT on
      inflammatory biomarkers, there is no definitive evidence that change in these
      markers results in modification of cardiovascular risk.

PMID- 14723061
TI  - [Commitment hierarchy of the Geneva declaration].
AB  - There is a revival at present in the use of the medical oath. A study of the text
      is necessary from the first year of study in medical school. The aim of this work
      was to know how medical students rank the commitments of the Geneva Declaration.
      One hundred seventy 1st-year students were evaluated. They were asked to
      enumerate the commitments in a hierarchy according to their perception of medical
      work. The greatest percentages of the principles for each position were obtained.
      The commitments placed first were respect to life (39.4%), consideration of
      patient health as first concern (23.5%), and non-discrimination (27.1%). Votes
      placed last in the ranking were related to honor and professional traditions
      (24.1%) and consideration of colleagues as brothers (28.8% and 44.7%). The
      difference among percentages was significant, mainly with regard the last
      commitment. Medical students located in the first places obligations with
      reference to ethical principles of physician-patient relationship, considering
      less relevant commitments with the profession and its members. It will be of
      interest to determine the reason for this dichotomy and to encourage reflection
      upon medical oaths, generating greater commitment.

PMID- 14723062
TI  - [Contributions of women in medicine].

PMID- 14723063
TI  - By the numbers. Health care economics.

PMID- 14723064
TI  - By the numbers. Hospitals/healthcare systems.

PMID- 14723065
TI  - By the numbers. Post-acute.

PMID- 14723066
TI  - By the numbers. Medicare/Medicaid.

PMID- 14723067
TI  - By the numbers. Physicians.

PMID- 14723068
TI  - By the numbers. Drugs/purchasing.

PMID- 14723069
TI  - By the numbers. Staffing.

PMID- 14723070
TI  - By the numbers. Vital statistics.

PMID- 14723071
TI  - By the numbers. Insurers/managed care.

PMID- 14723072
TI  - By the numbers. Information technology.

PMID- 14723073
TI  - Killer credentials. In wake of nurse accused of killing patient, the health
      system wrestles with balancing shortage, ineffectual reference process.
AB  - In the past two years Somerset Medical Center has sunk $12 million into a
      clinical information system designed to ensure patient safety. But that
      technology couldn't stop a nurse, Charles Cullen, left, allegedly bent on harming
      patients. The case highlights some disturbing gaps and disconnects in a
      fragmented employment system.

PMID- 14723074
TI  - Charity under fire? Providers say regs prevent them from giving care.

PMID- 14723075
TI  - If at first you don't succeed... bankrupt companies buy back their own assets.

PMID- 14723076
TI  - Heavy costs. Hospitals pay high price to treat obese patients.

PMID- 14723077
TI  - Joining forces in California. Unions team up to fight Schwarzenegger budget.

PMID- 14723078
TI  - Year in review 2003. The stories that shaped, shook healthcare.

PMID- 14723079
TI  - Translating dreams into reality. It's up to regulators, private sector to carry
      out best intentions of Congress.

PMID- 14723080
TI  - Medicare reform opinions. All seniors gain benefits.

PMID- 14723081
TI  - Medicare reform opinions. Providers get help in caring.

PMID- 14723082
TI  - Medicare reform opinions. Opening door to choices. Medicare reform opinions.

PMID- 14723083
TI  - Medicare reform opinions. Flawed program needs fixing.

PMID- 14723084
TI  - Hospitals' holiday wishes come true. Behind the drug benefit is a lot of help for
      hospitals, especially rural providers.

PMID- 14723085
TI  - Quality initiative gets serious. Hospitals that want full reimbursement update
      must be in 'voluntary' effort.

PMID- 14723086
TI  - Niche facilities hit. Moratorium raises new self-referral issues for docs.

PMID- 14723087
TI  - Marketing Medicare. Legislation would force federal program to compete with
      private sector.

PMID- 14723088
TI  - Seniors finally get help. Drug support limited by 'doughnut hole,' costs.

PMID- 14723089
TI  - PBMs get new role. Seen as key to drug cost control under new benefit.

PMID- 14723090
TI  - Docs take a deep breath. $3 billion payment cut averted as they win slight raise;
      problems remain.

PMID- 14723091
TI  - Guarding against i.v. errors. Software alerts nurses to potentially harmful
      mistakes in drug dosages.

PMID- 14723092
TI  - Eat, drink and be wary.

PMID- 14723094
TI  - Management of bronchiectasis.
AB  - Around 1 in 1,000 adults in the UK has bronchiectasis, a potential outcome of
      various underlying lung diseases. It results from a 'vicious circle' of recurrent
      infection, inflammation, excessive mucus production, reduced mucociliary
      clearance, and dilatation and destruction of bronchi. Associated damage to blood
      vessels can lead to haemoptysis, which is usually slight, but may be severe.
      Bronchiectasis may be limited to one area (localised) or be more widespread
      (generalised). It can reduce lung function and quality of life, and may lead to
      respiratory failure and premature death. Here we review the management of
      patients with bronchiectasis.

PMID- 14723093
TI  - Evra--a patch on oral contraception?
AB  - Evra (Janssen-Cilag) is the first contraceptive to be available as a skin patch.
      In promotional material aimed at healthcare professionals, the company claims
      that Evra offers a "once-weekly method of contraception" with "more than 99%
      effectiveness and excellent compliance". The company's website for women using
      Evra carries the slogan "Evra The Right Contraceptive Choice" and claims that the
      patch is "just as effective as the contraceptive pill". Each patch is intended to
      be worn for 7 days, in contrast to combined oral contraceptives (COCs), which
      need to be taken daily. Here we assess whether Evra offers real advantages over
      COCs and consider its place as a contraceptive option.

PMID- 14723095
TI  - NCQA to look more closely at issues small employers care about.

PMID- 14723096
TI  - Aloha state never expected such a long goodbye to uninsured.

PMID- 14723097
TI  - Compensation monitor. Family physicians paid less per RVU than internists.

PMID- 14723098
TI  - Dr. Do-good and Mr. Bottom-line.

PMID- 14723099
TI  - Health plans begin to address chronic care management.

PMID- 14723100
TI  - Will new benefit design harm some patients?

PMID- 14723101
TI  - Why do FEHBP and big unions excel at managing drug costs?

PMID- 14723102
TI  - Can amylin analogue lead to better diabetes control?

PMID- 14723103
TI  - 'What can you do to help control costs?'.

PMID- 14723105
TI  - The formulary files. Electronic prescribing has no effect on formulary
      compliance.

PMID- 14723104
TI  - Treating psoriasis patients with biologic agents.

PMID- 14723106
TI  - Managed care outlook. Simple math: health plans' robust performance spurs merger
      and acquisition interest.

PMID- 14723107
TI  - Dry eye moves beyond palliative therapy.
AB  - Keratoconjunctivitis sicca, or dry eye syndrome, is a complex condition
      characterized by inflammation of the ocular surface and tear-producing glands.
      Emerging awareness of the etiology of dry eye has led to the development of
      highly effective therapy. When dry eye is controlled, there is significant
      potential for cost savings.

PMID- 14723108
TI  - Dry eye: prevalence, utilization, and economic implications.
AB  - Dry eye syndrome is far more prevalent than previously considered. There are
      significant comorbidities, associated diseases, and behavioral and environmental
      factors that may contribute to the severity of dry eye. Dry eye syndrome has
      significant economic implications, including costs associated with increased
      health care utilization, missed school and work, and leisure and quality-of-life
      issues. Dry eye presents important economic challenges to patients, physicians,
      and health care delivery organizations.

PMID- 14723109
TI  - Inflammation: a unifying theory for the origin of dry eye syndrome.
AB  - Dry eye syndrome has been difficult to diagnose and treat, due to its
      heterogeneity. These difficulties are being overcome, however, as evidence
      becomes available about a common etiology. An inflammatory mechanism apparently
      underlies the condition. This theory has been proven by use of immunomodulators
      that show efficacy in treating patients with dry eye syndrome.

PMID- 14723110
TI  - Guidelines for the treatment of chronic dry eye disease.
AB  - Keratoconjunctivitis sicca (KCS), also known as dry eye syndrome, dry eye
      disease, chronic dry eye disease, or keratitis sicca, refers to disorders of the
      tear film caused by reduced tear production, poor tear quality, or excessive tear
      evaporation. These disorders are associated with such symptoms of ocular
      discomfort as irritation, foreign body sensation, or redness, and may cause
      disease of the ocular surface.

PMID- 14723111
TI  - Medications for dry eye syndrome: a drug-therapy review.
AB  - Early interventions were palliative, attempting to replace water lost from the
      tear film. Today, therapy is directed at the underlying inflammation, a
      recognized component of dry eye syndrome, and at the resulting progressive
      changes to the ocular surface. This approach offers promise of lasting relief to
      patients with moderate to severe symptoms.

PMID- 14723112
TI  - Considerations in the pharmacoeconomics of dry eye.
AB  - Dry eye disease diminishes the quality of patients' lives and drives utilization
      of health care resources. Until recently, all treatments for dry eye have been
      palliative. A new treatment, cyclosporine A ophthalmic emulsion, addresses the
      disease's underlying causes. It warrants pharmacoeconomic analysis to determine
      its place in managed care.

PMID- 14723113
TI  - Issues in the use of preservative-free topicals.
AB  - In a perfect world, patients would use medications as prescribed. In reality,
      patients may cut corners, especially if they may save money by doing so.
      Clinicians and pharmacists must acknowledge this tendency, yet at the same time
      protect patients from using contaminated ophthalmologic agents and strive to
      achieve optimal clinical outcomes.

PMID- 14723114
TI  - Medicare agreement: premium support demo ... maybe.

PMID- 14723115
TI  - Perspectives. What the drug benefit looks like now.

PMID- 14723116
TI  - Doctor-patient e-mail getting hotter.

PMID- 14723117
TI  - What's it worth?

PMID- 14723118
TI  - Integrating the consumer and clinical sections of your organization's site.

PMID- 14723119
TI  - Deaconess Billings Clinic moves toward integration of clinical and consumer Web
      functions.

PMID- 14723120
TI  - [Conceiling the cadaver in masonry and cement].
AB  - Encasing with concrete and/or bricks are relatively rare forms of hiding or
      disposing of a body; criminologically, cases of this kind are often treated as
      "matters involving a missing person" at first. The article describes the
      circumstances and findings of 2 cases in which bodies were encased with concrete.
      Under the aspects of reconstruction it is of importance that bodies may be
      preserved quite well in concrete, which allows not only identification of the
      victim but also determination of the cause of death even after a prolonged post
      mortem interval, the more so as occasionally tools used for committing the
      offense are also encased together with the body.

PMID- 14723121
TI  - [Immunochemical screening: manipulation, handling and interpretation errors,
      exemplified by benzodiazepines].
AB  - The article describes problems related to immunochemical screening-tests with
      special regard to benzodiazepines, which are commonly used for therapeutic
      purposes. Focal points are adulteration, manipulation and handling of samples,
      the selection of cut-off-values, specificity and cross-reactivity, influence of
      biotransformation and frequently observed pitfalls in the interpretation of the
      analytical results.

PMID- 14723122
TI  - [Rare pattern of injuries after being run over by a railroad train ].
AB  - The article reports on findings after a suicide committed by being run over by
      the driving unit of an ICE train in a railway station. After recovering the body
      a fresh abrasion was found on the right upper abdomen with a minor laceration.
      Some hours later a circular abrasion mark and zones of contusion were discernible
      on the trunk. Whereas the integument was largely intact, the spine was severed
      and inner organs of the trunk were ruptured.

PMID- 14723123
TI  - [A hopeless case?].
AB  - In a hollow covered with earth, a herb gatherer discovered a severely decomposed
      corpse mutilated by scavenging animals. Only small areas of the skin had remained
      intact. A conspicuous tattoo could still be distinguished on the left upper arm.
      Despite concrete evidence of violence (fracture in the occipital bone, subdural
      hemorrhage with a volume of 20 ml), the exact cause of death could no longer be
      established. Police enquiries identified a person in whom such a conspicuous
      tattoo had been photographed in an earlier criminal case. Eventually, the
      deceased person could be identified by DNA analysis of a stored blood alcohol
      specimen. Considered together, the autopsy findings and the results of the
      investigation of traces of blood on the putative tool used in the crime indicated
      that the man had been struck dead and the body had afterwards been buried in the
      wood. Although the prospects of success had been initially slight, it was not
      only possible to identify the victim, but also to reconstruct the crime.

PMID- 14723124
TI  - [Homicidal alcoholic intoxation versus manual neck compression].
AB  - A case of homicide involving a 49-year-old man is reported. In the course of a
      booze-up he was forced to excessive consumption of alcohol and was pushed back
      into a sofa by repeated grasping his neck which finally left him dead. The
      postmortem examination revealed a small abrasion in the right mandibular region,
      a contusion of the subcutaneous tissue above the left clavicle, a haemorrhage in
      the deep muscles of the neck at the right side of the cervical spine, a fatty
      tissue haemorrhage between the left cornus of hyoid and thyroid cartilage as well
      as petechiae of the eyelids and conjunctivae. The blood alcohol concentration
      amounted to 4.00@1000, the urine alcohol concentration to 5.26@1000. Thus, a
      manual strangulation of the neck versus a lethal alcohol intoxication had to be
      taken into consideration as cause of death. The morphological findings of the
      postmortem examination and the pathophysiological concepts of the underlying
      mechanisms of death in manual strangulation versus lethal alcohol intoxication
      are discussed with regard to their significance for the juridical assessment.

PMID- 14723125
TI  - [Report on a methemoglobin-associated fatality].
AB  - An autoerotic fatality due to mechanical compression of the neck by a
      sophisticated construction used for breath control games is reported. The
      presence of signs of methemoglobinemia as well as an empty "poppers" flask found
      beside the passed indicated the use of volatile nitrites to enhance sexual
      pleasure. It was assumed that vasodilatation had caused a sudden unconsciousness
      with consecutive hanging.

PMID- 14723126
TI  - [Current status and perspectives of using radioprotectors in clinical practice].
AB  - In this contribution an attempt is made to look at the theoretical aspects of
      effects of radioprotectors. Experimental and clinical data were presented.
      Sulfhydryl compounds are the most effective radioprotectors known nowadays, but
      there are two main problems of its using. The first one is their toxicity and the
      second--short-ranged activity. The unique radioprotector widely used in clinic on
      application of cytostatic therapy is amifostine. Many clinical trials have shown
      amifostine first of all to be useful in managing xerostomia in patients with head
      and neck tumors after receiving polychemotherapy. Low-to-moderate doses of some
      agents such as nitroxides, adrenoceptor agonist etc were found to have
      radioprotective activity in experiments but their application in clinic remains
      doubtful.

PMID- 14723127
TI  - [Neurobiology and modern approaches to the treatment of Alzheimer disease].
AB  - Alzheimer's disease (AD) is the most common type of dementia among older people.
      AD is characterized as neurodegenerative disease showing impairment of cognitive
      function, death of neuronal cells, numerous numbers of senile plaques and tangle
      of neurofilaments. The paper contains the literary review concerning the most
      important neurobiological mechanisms of the AD development. The modern strategy
      of treatment such as acetylcholine esterase inhibitors, neuroprotectors,
      neurotrophic factors, inhibitors of beta- and gamma-secretase, beta-amyloid
      aggregation inhibitors, beta-amyloid degradation stimulators, beta-amyloid
      vaccination, inhibitors of tau protein phosphorylation, estrogens, nonsteroid
      anti-inflammatory drugs is discussed.

PMID- 14723128
TI  - [Analysis of peculiarities of magnetic field effect].
AB  - In the article is analyzed the influence of a magnetic field of the Earth on
      human, state of his health and necessity of magnetic diagnostics. The magnetic
      fields is an effective preventive and tentative method in case of an early
      development of diseases.

PMID- 14723129
TI  - [Publishing--weighty characteristic of scientific productivity (analysis of
      scientific publications of 15-years period since Chernobyl catastrophe)].
AB  - We have carried out a complex analysis of scientific reports of the RCRM for the
      last 15-years since Chernobyl holocaust. One may notice considerable growth of
      circulation and quality coefficient of publication of scientific research. The
      tendency shape of the publications over a period of 1986-2001 looks like a
      straight line and dynamics of references on RCRM publications--an exponential
      curve. Degree of scientific effort connected with priority directions of the RCRM
      considerably exceed similar indices in the world. Studies of immunological and
      hematological irradiation effects, radiation shielding of population, radiation
      impact on a fetus and offspring are being carried out most intensively nowadays.
      The article highlights the innovations in the work of the center as a leading
      part of the research of the RCRM closely tied with the Chernobyl tragedy and its
      medical consequences, urgent need to improve and develop methodical and directive
      documents to make better health care management of Ukrainian people suffered from
      Chernobyl disaster. The above-mentioned consequences and accumulated experience
      of their resolution having global character, are not only important for Ukraine,
      but also have an international value.

PMID- 14723130
TI  - [Clinical and instrumental predictors of survival in patients with chronic heart
      failure and intact systolic left ventricle function].
AB  - 165 patients with clinically-manifested chronic heart failure (CHF) and preserved
      (ejection fraction--EF > 40%) left ventricular (LV) systolic function have been
      investigated. 135 of them have ischaemic heart disease (IHD) and high blood
      pressure, 8 patients are without IHD and 22 patients with normal blood pressure.
      62 patients have chronic atrial fibrillation. Survival value in patients with CHF
      and preserved LV systolic function was compared to survival value of those with
      CHF and impaired ejection fraction (EF < 40%). Patients with preserved LV
      systolic function have been found to be with better survival value than those
      with impaired ejection fraction (68 and 33% accordingly).

PMID- 14723132
TI  - [Structural and metabolic aspects of heterogenicity of the ventricular cardiac
      myocytes in coronary insufficiency].
AB  - The paper shows comparative analysis of structural-metabolic changes of the
      ventricular cardiac hystiocytes during transitional restriction of blood supply,
      which leads to relapsing myocardium hypoperfusion, ischemia and even to cardiac
      infarction. We have established that an increase of the myocardium
      arrhythmogenicity, damage of myocardium electrophysiological activity and
      coronary deficiency are caused by pathologically intensified structural-metabolic
      heterogeneity of cardiomyocites. The chronic ischemic heart disease is worsening
      the situation by gradual accumulation of the metastructure changes of heart's
      working cells. It is possible to connect adaptable hypertrophy of cardiomyocites
      with compensatory redistribution of loading among them, what is accompanied with
      the deep reorganization of their metabolism and metastructure under the influence
      of neurohumoral factors, inadequate transport-trophic maintenance of the
      function, nonequal edema and fibrosis of the interstitium. The data obtained
      describe the formation of "prereadiness" of the myocardium to the fatal rhythm
      disturbance determined by interconnected structural-metabolic changes. Each of
      these pathological changes separately doesn't induce an impairment of myocardium
      electric stability but represents a necessary part in origin and development of
      the pathological process.

PMID- 14723131
TI  - [Approaches to the treatment of hypertension].
AB  - The article criticizes a standard approach to essential hypertension treatment
      based for the most part on b-adrenoblokers, calcium channel blockers and
      angiotensin-converting enzyme inhibitors. The author proposed an individual
      approach to managing hypertension based on Lang neurogenic theory with taking
      into consideration different types of hypertensive attacks.

PMID- 14723133
TI  - [Characteristics of the biochemical blood indices in patients with pulmonary
      tuberculosis complicated with chronic bronchitis].
AB  - We have studied the oxidant-antioxidant, serum protease inhibitor systems and
      serum proteolytic activity in patients suffering from pulmonary tuberculosis
      complicated with chronic bronchitis. The indices of these systems were shown to
      be unconnected with the duration of tuberculosis, its clinical appearances and
      concomitant chronic bronchitis, but mark severity of the specific process.

PMID- 14723134
TI  - [Vascular tone in adolescents with autonomic vascular dysfunction of hypotensive
      type (according to the data of tetrapolar rheovasography)].
AB  - 408 teenagers at the age of 11-14 y.o. have been investigated. All of them
      underwent tetrapolar longitudinal reovasography. 339 were found with hypotensive
      type vegetovascular dysfunction. It was established, that the vascular component
      plays an essential part in genesis of vegetovascular disfunction; vessels are
      losing their elasticity, that leads to decreasing of vascular tone, blood filling
      of some parts of the body, decelerating pulse-wave velocity, at the end
      transforming in steady decreasing of arterial tension.

PMID- 14723135
TI  - [Characteristics of motor activity disorders in patients with vertebrogenic
      lumbosacral pain syndrome].
AB  - The study is based on clinical examination of movement disorder in 126 patients
      (men--103, women--23) with lumbosacral pain syndrome. The authors revealed how
      statico-dynamic and neurotic disorders had been formed depending on structural
      peculiarities of primary pathologic process and thus determining different
      clinical forms. Mechanisms of syndromologic manifestation of suffering in every
      case were substantiated; own approaches to anatomico-topical diagnostics and
      objectification of pathology course in dynamic were suggested.

PMID- 14723136
TI  - [Specificity of endometrium phospholipids and their fatty acids changes in the
      development of hyperplasia].
AB  - Quantitative changes in phospholipids (PL) and fatty acids content (FA) in
      patients with endometrium hyperplasia have been revealed. During observing
      endomentrium hyperplasia process we found out on the one hand reliable decrease
      in phosphatidylethanolamine (PEA), phosphatidylcholine (PC) content and on the
      other hand increase of its lysoforms. Changes in unsaturated fatty acids (PA n-6)
      -arachidonic (AA) content and docosahaenoic (DHA) acids content were also shown.
      The decrease of PC, PEA in patients with endometrium hyperplasia is interrelated
      with quantitative change of plasmalogenic phospholipids PL, which is too much
      sensitive to oxidative reactions and at the same time able to protect sells
      against oxidative stress. Considerable decrease in plasmenyl PEA content on the
      one side and plasmenyl PC content stability on the other was revealed in patients
      with endometrium hyperplasia. Above mentioned lipid metabolic derangements of the
      endometrium are specific with respect to different classes of phospholipids and
      their fatty acids composition.

PMID- 14723137
TI  - [Prevalence of undiagnosed celiac disease in patients with irritated bowel
      syndrome].
AB  - In the article insufficiency of existing patterns of investigation of patients
      with irritated bowel syndrome (IBS) during differential diagnostics with celiac
      disease is underlined, that leads to wrong diagnostics and inefficient treatment
      of patients. Also own data on prevalence of celiac disease in patients with IBS
      are shown. Determination of the level of specific markers of celiac disease (in
      our research--antigliadin Ig) is considered to be the optimal method of
      diagnostic celiac disease in this group of patients.

PMID- 14723138
TI  - [Effect of smoking on gastric mucosa acidity and contamination with Helicobacter
      pylori in patients with duodenal ulcer].
AB  - We have compared acidity level and Helicobacter Pylori contamination rate of the
      mucous coat of stomach in 50 patients with duodenal ulcer at the age from 17 to
      54 y.o., among which were 25 smokers and 25 non-smokers. The period of smoking
      varied from 5 to 21 years. In the morning Ph-measurements were carried out by
      means of IAS-2 device based on V. N. Chernobrov's method. We used
      fibrogastroduodenoscopy technique for verifying a duodenal ulcer and obtaining
      mucous coat material from antrum and corpus ventriculi to obtain Helicobacter
      Pylori contamination rate. The acid level of the stomach in the smokers was shown
      to be reliably lower than in non-smoking patients, what was the cause of higher
      Helicobacter Pylori contamination rate.

PMID- 14723139
TI  - [Specificity of ferrokinetics in children with enzymopathy of small intestine].
AB  - 154 children with intestinal enzymopathies have been investigated. 57 of them
      were with celiac disease, 52--with multi-enzymatic deficiency syndrome (celiac +
      disaccharides deficiency), 45--with disaccharidase deficiency syndrome. The
      typical changes in blood of children with intestinal enzymopathies were presented
      in decreasing of MCV, MCH, MCHC and increasing of RDW. The study of ferrokinetics
      has shown that an anemia was caused by deficiency in many elements with
      predominance of iron-deficiency erythropoesis. The most sensitive and reliable
      indicators of early detection of latent anemia without decrease in hemoglobin
      level were ferritine content, the coefficient of saturation of transferrine and
      transferrin's receptors.

PMID- 14723140
TI  - [Palliative combined chemotherapy in patients with inoperable primary liver
      cancer].
AB  - The subjective, objective evidences of status of 61 patients with primary liver
      cancer were studied. The patients were divided into two groups. The first group
      underwent a course of chemotherapy, the second group--combined chemotherapy with
      ericsin as an immunomodulator. Decrease of pain sensation, less side effects of
      treatment, improvement of general state and life style of the patients were
      observed in the second group thus giving us an opportunity to run refresher
      courses of treatment.

PMID- 14723141
TI  - [Modern principals of antibacterial therapy of suppurative-septic diseases].
AB  - The carried out researches concerning initial nidus of infection have shown a
      high rate of anaerobic infection especially in patients with destructive
      suppurative lung disease, liver abscess, peritonitis (up to 82.8%). An aerobic
      anaerobic association of microbes remarkably often is found in the nidus of
      infection. We recommend the following preventive scheme to treat patients with
      different pyoseptic diseases. The scheme is based on the results of our 10 years
      experience treatment of such patients. It consists of a combination of 2.0 gr.
      cefoperazoli twice daily, metronidasoli 500 mg. 3 times and amycacini 500 mg
      twice daily. The intra-arterial or intravenous introduction of the medications
      was possibly preferred. Having analyzed the results of the treatment of 13,747
      patients treated at the center of contaminated surgery, we would note that in
      30.2% of the cases were reached excellent results. The above-mentioned scheme of
      antibacterial therapy with surgical correction of suppurative focus allowed us to
      reach good results in 45.4%. The satisfactory results of the treatment were
      achieved in 22.8% of patients. Mortality rate was up to 1.9%.

PMID- 14723142
TI  - [Using phospholipids modified according to the method of liposome technology in
      the treatment of patients with chronic renal insufficiency].
AB  - The article deals with treatment of chronic renal insufficiency, which is an
      issue of the day. 35 patients with chronic renal insufficiency (CRI) at I-II
      stages irrespective of primary nosological diagnosis have been investigated. It
      was the first time when LIPIN was prescribed at a total dose of 20 mg/kg to
      improve the methods of conservative therapy. The material presents dynamics of
      laboratory indices of renal function over treatment with LIPIN. It was
      established, that LIPIN statistically reliably decreases creatinine and urea
      level in patient's blood, absolutely brings down transmidase blood serum
      activity, reduce clinical presentations of uremic gastroenteropathy as well as
      improves general state of health.

PMID- 14723143
TI  - [Immunosuppressive therapy in multiple sclerosis].
AB  - Results of the examination of more than 51 patients with multiple sclerosis and
      20 patients of the control group are presented in this article. It is shown that
      therapy with immunosuppressive medicines (metilprednisolon, dexametason and
      synakten-depo) is effective as treatment of patients with multiple sclerosis at
      the stage of exacerbation, making positive effect on the dynamics of the
      neurological symptoms and immunal indices. The best results were observed among
      the patients of II and III level of gravity with mainly remitting type of
      multiple sclerosis. In the comparative aspect pulse-therapy with metilprednisolon
      was the most effective.

PMID- 14723144
TI  - [Prevalence, diagnostics, and therapy of psychotic disorders among general
      somatic diseases].
AB  - The paper presents observational data of depression extent among general
      patients. Psychosomatic disorders are considered in the article. The authors
      analyzed the mental disorders incidence among different groups of somatic
      patients, a problem of using the various treatment techniques in these groups.
      Authors propose the treatment of depression observed among general patients; it
      is based on literature data and their own observations.

PMID- 14723145
TI  - [Diagnostic algorithms of morphological parameters of the thymus gland in the
      development of various diseases in premature infants].
AB  - The authors have investigated the morphological and morphometrical signs of
      thymus glands in prematurely born children died of different causes and worked
      out the algorithm of morphological signs coming along with this or that
      pathology. It was shown, that weight and weighting coefficient of the thymus
      gland correlate with degree of child prematurity and different causes of death.
      Drawing up the algorithm of the morphological changes to determine pathology of a
      thymus gland gave us an opportunity to establish criteria of normal development
      of a thymus gland and its developmental lagging, hypoplasia, dysplasia, premature
      atrophy against a background of incomplete pregnancy and different diseases. The
      data can be used as diagnostic criteria for evaluating morphological structure of
      the thymus gland of a newborn infant.

PMID- 14723146
TI  - [Sclerotherapy of solid nodules in the thyroid gland].
AB  - We have studied long-term effects (3-8 years) of transcutaneous sclerotherapy
      with ethanol in a group of 123 patients at the age from 17 to 87 y.o. The
      patients had benign solid nodular formations of thyroid gland at volume from 0.7
      to 162.8 ml. It was revealed, that a reduction degree of the solid nodular
      formations don't depend on ingoing sizes. The efficiency of sclerotherapy first
      of all is up to internal structure of the solid nodular formation and its stroma
      structure development.

PMID- 14723147
TI  - [Hepatotoxic effect of etacizin in acute pneumonia].
AB  - The paper describes one acute toxic hepatitis event in a woman of 60 with
      pleuropneumonia and exudative pleurisy. She had been treated with ethacizinum in
      small dose. To solve the problem, antioxidant and drug with hepato protective
      action should be prescribed along with ethacizinum.

PMID- 14723148
TI  - [Difficulties in diagnostics and complications of Wegener's granulomatosis].
AB  - The authors substantiate their opinion based on literature data as for the
      difficulties of Vegener granulomatoses diagnostics. These are middle and small
      sized vessels where the pathologic process takes place. The pathologic process
      being systemic is not easy to be well timed diagnosed; furthermore the illness
      often becomes complicated. The authors give two examples of such complications
      (pulmonary-cardiac insufficiency and spontaneous pneumothorax) and consider that
      vivid clinical picture of these complications would help a physician in
      diagnostics of the disease.

PMID- 14723149
TI  - [Effect of the treatment with fenigidin on peripheral hemodynamics in patients
      with stable angina pectoris].
AB  - Peripheral arterial and venous hemodynamics were investigated by plethysmography
      method in 32 patients with functional classes II-III angina pectoris. The course
      of phenihidinum treatment in daily dose of 30-40 mg during three weeks was found
      beneficial on arterial and venous tone. The therapy decreases pre- and heart
      afterload in such patients without any side effects.

PMID- 14723150
TI  - [Spirulina: perspectives of the application in medicine].
AB  - The data on biologically active components included in structure of blue-green
      seaweed spirulina, determining its value as food additive and medicinal means are
      submitted. The results of use of spirulina in experimental models of pathology
      and clinical practice are generalized.

PMID- 14723151
TI  - [Solcoseryl--new preparation for the pathogenetic treatment of patients with
      paroxysmal forms of cerebrovascular pathology].
AB  - The central goal of the investigation was to study Solcoseryl (SolcoSwitzerland)
      therapeutic efficacy for patients suffering from early or chronic cerebrovascular
      diseases complicated with different forms of paroxysms. 29 patients were
      examined. (14 of them were with vegetovascular dystonia, 7 with discirculatory
      encephalopathy of degree of 1 and 8 with discirculatory encephalopathy of degree
      of II). The authors revealed Solcoseryl to be positive in decreasing incidence
      and duration of vegetovascular fits, complaints, pathologic symptoms.

PMID- 14723153
TI  - [Assessment of the quality of ambulatory-polyclinic care of patients with
      diabetes mellitus].
AB  - Outpatient-policlinic care study of 1121 patients with diabetes mellitus (DM)
      over the period 1997-1999 shows that 82.5% of patients with non-insulin-dependent
      (type II DM) and 65% of patients with insulin-dependent diabetes (type I DM)
      hadn't been observed regularly. In 53.7% of type II DM cases and 64% of type I DM
      cases one might detect worsening of patients' state although the adequate
      treatment was prescribed in 91% of type II DM cases and 93% of those with type I
      DM. 44.6% of patients with type II DM and 33% of patients with type I DM hadn't
      remarked any changes of their health, only 0.8% of patients with type II DM and
      2.0% with type I DM were found with better clinical data. Unfortunately, one
      might say polyclinic rehabilitation work to be unsatisfactory in 83.7% of type II
      DM cases and in 78% of type I DM cases. As a result of this analysis it is
      essential to enlist general practitioners as well as nurses specialized in
      diabetes care to render medical aide to the diabetics.

PMID- 14723152
TI  - [Role of etiol (amifostine) in the treatment of patients with malignant
      lymphoma].
AB  - The material is devoted to using of amifostinum as cytoprotor during
      polychemotherapy application in patients with malignant lymphomas. 10 patients (5
      with lymphogranulomatosis, 4 with non-Hodgkin's lymphoma and 1 with Ewing's
      sarcoma) were receiving along with cytostatic therapy amifostinum. The patients
      treated with combined therapy had less side effects of polychemotherapy than a
      control group which had been receiving only polychemotherapy. The number of
      lymphocytes was constant in the group using amifostinum in contrast to another
      group where decrease of lymphocytes by 24% was noted. Owing to amifostinum we
      could complete the course of treatment even in patients whose state didn't allow
      us of sufficiently using polychemotherapy.

PMID- 14723154
TI  - [Status of the vision organs in military personnel of different armed forces of
      the Western operative command of Ukraine].
AB  - The article presents figures of physical development and sickness rate of
      military personnel in accordance with medical aid appealability data. In addition
      the authors give the information about organum virus morbidity among military
      personnels of Western Operative Command.

PMID- 14723155
TI  - [Variation of bacterioplankton number in the north-western part of the Black Sea
      depending on hydrological and hydrochemical factors].
AB  - Quantitative analysis of total bacteria numbers variations under influence of
      river outflow and development of anaerobic conditions has been carried out on the
      basis of long-term field research in the north-western part of the Black Sea. The
      regressive equations describing dependence of the total bacteria number on
      temperature, salinity and water saturation with oxygen have been calculated.
      These results allow to characterize more completely the regularities of
      eutrophication processes on the Black Sea shelf.

PMID- 14723156
TI  - [Antimicrobial activity of saponins from Hedera taurica C a r r].
AB  - The antibacterial and antifungal action of saponins Sx1, taurozide H2, taurozide
      I and their effect on bioluminescent system of photobacteria Photobacterium
      phosphoreum (Cohn) Ford were investigated. Saponins H2 and I had no antimicrobial
      effect. Saponin Sx1 possessed antifungal activity in vitro with respect to
      Candida albicans, C. krusei, C. tropicalis. Saponin Sx1 is less toxic to P.
      phosphoreum than well-known antiseptics--chlorhexedin and miramistin.

PMID- 14723157
TI  - Antiscleroma effectiveness of certain Bacillus subtilis strains studied in vitro
      and in vivo.
AB  - Antagonistic activity of approximately 200 Bacillus subtilis cultures vs.
      Klebsiella rhinoscleromatis clinical strains in experiments on solid and liquid
      nutrient media, and in experiments on laboratory animals has been studied. 16 B.
      subtilis strains characterized by a vivid antiscleroma activity in vivo have been
      selected. Maximum preventive and therapeutical influence of the B. subtilis
      strain 1119 upon the flow of experimental acute septic and lung scleroma
      infection has been determined. While co-cultivating the test cultures under study
      (B. subtilis 1119 and K. rhinoscleromatis 230), a significant titer decline and
      complete klebsiella's growth suppression on the 8th-12th days provided the
      certain concentrations of the antagonistic microbes have been shown.

PMID- 14723158
TI  - Biological activity of bacterial lectins and their molecular complexes with
      heterocyclic bis-adducts.
AB  - A new convenient method for the preparation of heterocyclic bis-adducts: of
      imidazole, benzimidazole, uracile with 1,1,1-trifluoro-2-bromo-2-chloroethane is
      described. The reactions are catalysed by the 18-crown-6-complex. The critical
      toxicity and antitumour activity of saprophytic strains Bacillus genus (B.
      subtilis 668 IMV and B. polymyxa 102 KSU) extracellular lectins were studies. It
      was discovered that these substances apply to a few toxic preparations and have a
      expression antitumour action on the tumours: Walker carcinosarcoma 256, Pliss'
      lymphosarcoma and Sarcoma 45. The new molecular complexes were created with
      bacterial lectins and the same heterocyclic-bis-adducts of unsubstituted
      benzimidazole and 6-methyluracile. A strongly antitumour effect of these
      complexes has been discovered: of growth relaxation of Pliss' lymphosarcoma
      tumour mass was 62.5-82.01%.

PMID- 14723160
TI  - [Microbiocenosis of lower extremities skin of healthy people and patients with
      diabetes mellitus].
AB  - A comparative study of the foot skin microbiocenosis of 50 healthy persons and 29
      patients with diabetes mellitus and diabetic foot syndrome have been carried out.
      It has been revealed that various topodemes had unequal degree of aerobic
      microorganisms colonization. Different species of staphylococci are dominating
      taxons in skin. The gradient of bacterial populations density in healthy and sick
      persons grows in a direction: back of the foot--sole--interdigital space.
      Modification of skin microbiocenosis in patients with diabetes mellitus has been
      shown. The colonization degree by different species of bacteria decreased; the
      bacilli part enhanced and the corynebacteria part decreased in the biocenosis
      composition.

PMID- 14723159
TI  - [Investigation of quantitative and species composition and antifungal drug
      susceptibility of yeasts isolated from patients with generalized periodontitis
      complicated by candidosis].
AB  - Biological properties of 68 Candida strains isolated from parodontal pockets of
      patients with generalized parodontitis complicated with candidosis have been
      investigated. It was established that 72.1 +/- 5.43% of strains belong to Candida
      albicans. The clinical Candida albicans isolates display high resistance to
      nystatin and levorin, but they are sensitive to synthetic antifungal drugs 5
      fluorocytosine, fluconazol, especially to ketoconazol, itraconazole and to
      antifungal antibiotic amphotericin B as well.

PMID- 14723161
TI  - [Chemotherapy of experimental rickettsial infection under the influence of small
      doses of radiation].
AB  - Radiation is of particular importance among a lot of environment factors
      dangerous for human health, including the effect of small dozes of radiation.
      State of rickettsial infection under the influence of small dozes of radiation
      and under administration of immunostimulator Imunal and antibiotic doxycyclin has
      been studied. Researches were conducted on guinea pigs, using the experimental
      rickettsial infection. Researches have shown that the use of immunostimulator
      Imunal and antibiotic doxycyclin had positive effect on the immunity indices of
      the experimental rickettsial infection in animals in the conditions of influence
      of small dozes of radiation.

PMID- 14723162
TI  - [Methods for estimation of microbe resistance of protective coatings].
AB  - Methods are proposed which permit estimating bioresistance of protective
      materials against denitrifying hydrocarbon-oxidizing and sulphate-reducing
      bacteria-destructors of coatings in laboratory conditions. The methods are based
      on the quantitative determination of bacteria growth in presence of coatings as
      the only source of hydrocarbon. Besides, attention is given to changes of certain
      indices of physico-mechanical properties of coatings: breaking strength and
      adhesion strength for coatings from polymeric bands, softening and expansion
      temperature for mastic materials.

PMID- 14723163
TI  - [Actual problems of bacteria phylogenetic classification].
AB  - Historical aspects of development of phylogenetic bacteria taxonomy and essence
      of species in systematics of bacteria are considered. Comparative analysis of
      phenotypic and phylogenic classification of bacteria is conducted. Basic results
      of 16S rRNA gene sequence for bacteria are adduced. Comparative estimation of
      molecular biological methods in microbiologic researches and also estimation of
      potentialities and shortcomings of 16S rRNA gene sequence-analysis in systematics
      of bacteria are conducted.

PMID- 14723164
TI  - [Mykhailo Ivanovych Shtutser--director of Research Institute of Microbiology and
      Epidemiology, PCE USSR (now Institute of Microbiology and Epidemiology of the
      National Academy of Sciences of Ukraine) in 1930].

PMID- 14723167
TI  - Perspectives. E-prescribing, formularies play big roles in Rx bill. 2.

PMID- 14723168
TI  - If foreign drug prices go up, will U.S. prices come down?

PMID- 14723169
TI  - [The origin of homoiothermy--unsolved problem].
AB  - The analysis of allometric dependence of energy expenditure on body mass among
      reptiles, birds and mammals has shown that standard metabolic rate of reptiles
      when they are warmed up to the temperature of homoiothermic animals is an order
      of magnitude lower than that of birds and mammals. Basal metabolism is originated
      as special feature historically related to the metabolism during active behavior,
      rather than thermal regulation. Facultative endothermy was not advantageous for
      large animals because of long time needed to warm up the body. The ancestors of
      birds and animals escaped negative consequences of van't-Hoff equation by
      choosing constant body temperature. Heat conductivity of reptile's covers is so
      great, that it cannot keep endogenous warm of resting animal at any temperature
      of the body. Reptile "dressed" in covers of bird or mammal would be able to keep
      warm under conditions of maximal aerobic muscular activity and body temperature
      similar to that of homoiothermic animals. The base of chemical thermoregulation
      in birds and mammals is a thermoregulatory muscle tonus which remains unknown.
      One can suppose that during evolution of birds and mammals the saltation-liked
      origin of endothermy "fixed" the level of metabolism typical for running reptile
      and transformed in into the basal metabolism. This event took place at the cell
      and tissue level. The absence of palaeontological evidences and intermediate
      forms among recent species does not allow easy understanding of homoiothermy
      origin.

PMID- 14723170
TI  - [Evolution of sex: role of deleterious mutation and mobile elements].
AB  - Prevalence of sexual reproduction is still enigma. The main character of sex is
      alleles mixing that could be advantageous either in unstable environment (in this
      case sex provides high temp of evolution) or in unstable genotype (in this case
      sex provides purge of genome from deleterious mutations). As long as not all
      species inhabit highly changeable environments, variation of genotypes is more
      important factor. As the majority of new mutations is deleterious, effective
      mechanism of genome purging is needed. Maintenance of "purging mechanism" may be
      a single role of sex. Two promising mutational hypotheses--clade selection
      (Muller's ratchet and Nunney's hypothesis) and mutational deterministic
      hypothesis of Kondrashov claim that more effective elimination of slightly
      deleterious mutations provides main advantage to sexual population in comparison
      with asexual. Despite prima facie similarity, these hypotheses differ in
      mechanisms, work at different temporal scales and have different consequences.
      Kondrashov's hypothesis reveals short-term advantage of sexual reproduction, and
      thus, based on the individual selection. Clade selection displays long-term
      advantage of sexual reproduction that could be realized only by group selection.
      The role of mobile elements in evolution of sexual reproduction is also
      discussed. Firstly, mobile elements ("sexual molecular parasites") can complicate
      the problem: having been domesticated in asexual genomes and remaining active in
      sexual genomes they lead to higher mutational rate in sexual organisms and so
      violate assumption critical for both mutational hypotheses of "other things being
      equal". Secondly, mobile elements could be leader factor of origin of sex
      (hypothesis proposed by Hickey). Because theory of group selection could explain
      maintenance of sex, but not its origin, mobile elements could induce the origin
      of sex but were not able to maintain it, so the next scenario of evolution of sex
      is proposed: mobile elements induced origin of sex, which was established later
      by group selection because provided long term benefit (Muller's ratchet and
      Nunney's hypothesis). So, on all stages of evolution, sex was not advantageous
      for the organism per se.

PMID- 14723171
TI  - [Geographical pattern of plant affinity to different communities and its causes
      (by the example of North-European forests)].
AB  - The same vascular plant species occur in communities of different types in
      different parts of their ranges. This phenomenon can be traced in both the
      latitudinal and the longitudinal directions. Changes in plant affinity to
      communities of different types are viewed by the example of the North-European
      forest studied in 1993-2001. Species occurring near their range limits, prefer
      habitats with smoothed amplitudes of minimum factors ("the law of preference for
      non-varying environments"). That's why Oxalis acetosella and other boreal-nemoral
      species demonstrate affinity to riparian forests of the middle-boreal subzone.
      Another cases of latitudinal change in ecological behavior may be caused by
      decrease in competitive ability (in Milium effusum), respective changes in the
      regeneration niche (in Cystopteris fragilis), or behavior of birds dispersing
      seeds (in Lonicera xylosteum). The longitudinal variation in plant behavior, as
      viewed by the example of the European-Siberian riparian-subalpine tall-herb
      synusia, is connected with the post-glacial plant migration in the European
      North. There is a lot of evidence for the individualistic character of the
      process, but it looks coherent in the historical retrospective. The possible role
      of refugia and long-distance dispersal in the process of formation of the present
      day ranges of species is briefly reviewed. Conditions for plant dispersal in the
      past seemingly differ from those nowadays observed. The principal factor, which
      governs the dispersal rate, is that of interspecific competition level. Plant
      dispersal could be rather fast in the course of the corresponding primary
      succession following the glacier retreat or the marine retrogression (the
      "impulse" hypothesis). Since the climax pattern is established running waters and
      disturbed lands serve as "migration channels" for plants.

PMID- 14723172
TI  - [The system of flowering plants: synthesis of classical and molecular
      approaches].
AB  - The proposed system of flowering plants (Angiospermae) is based on synthesis of
      cladistic researches from different authors, morphological data and "traditional"
      systematics as well. Classis Angiospermae is divided for 4 subclassis:
      Magloliidae, Liliidae, Rosidae and Asteridae. Thus, monocots belong to subclassis
      Liliidae, and so-called "dicots" to three other subclasses. Altogether there are
      35 orders and 328 families of flowering plants in this system.

PMID- 14723173
TI  - [R. Goldschmidt and J. Huxley: creative parallelisms].
AB  - The comparative analysis of scientific heritage of Richard Goldschmidt and Julian
      Huxley shows convincingly the resemblance of these two scientists' views over the
      core problems of evolutionary theory, genetics and development biology. They both
      contributed to developing a triad "genetics--development--evolution". The problem
      of a relative growth of animals was the central point in both Goldschmidt's and
      Huxley's works. Huxley developed a formula of the allometric growth (law of
      constant differential growth) while Goldschmidt was the first to draw up the
      broad interpretation of the consequences of that phenomenon. Both scientists
      belonged to initiators of development genetics and used the "non-morganian"
      genetics in their efforts of solving problems of macroevolution. Goldschmidt
      tended toward an idea of an important role of macromutation in the process of
      macroevolution, though Huxley adhered to more moderate views. But at the same
      time the concept of preadaptive mutations proposed by Huxley was close to
      Goldschmidt's idea of macromutants. It is shown that both scientists analyzed
      profoundly the changes in early stages of embryogenesis in respect to
      macroevolution. It is not likely to be reasonable to oppose firmly Goldschmidt's
      saltationism to the evolutionary synthesis of Huxley. They developed the larger
      biological problems in a similar way, and undoubtedly their works in the field
      helped to enrich the development of the views over genetics and evolution. The
      open-minded analysis of Goldschmidt's and Huxley's concepts leads to creating
      modern and up-to-date views over the theory of evolution where seemingly
      incompatible things go together rather well and supplement each other. Evo-Devo
      rediscovered Goldshmidt's Biology and Huxley's Synthesis.

PMID- 14723174
TI  - Leading by feel.
AB  - Like it or not, leaders need to manage the mood of their organizations. The most
      gifted leaders accomplish that by using a mysterious blend of psychological
      abilities known as emotional intelligence. They are self-aware and empathetic.
      They can read and regulate their own emotions while intuitively grasping how
      others feel and gauging their organization's emotional state. But where does
      emotional intelligence come from, and how do leaders learn to use it? In this
      article, 18 leaders and scholars (including business executives, leadership
      researchers, psychologists, an autism expert, and a symphony conductor) explore
      the nature and management of emotional intelligence--its sources, uses, and
      abuses. Their responses varied, but some common themes emerged: the importance of
      consciously--and conscientiously--honing one's skills, the double-edged nature of
      self-awareness, and the danger of letting any one emotional intelligence skill
      dominate. Among their observations: Psychology professor John Mayer, who co
      developed the concept of emotional intelligence, warns managers not to be
      confused by popular definitions of the term, which suggest that if you have a
      certain set of personality traits then you automatically possess emotional
      intelligence. Neuropsychologist Elkhonon Goldberg agrees with professors Daniel
      Goleman and Robert Goffee that emotional intelligence can be learned--but only by
      people who already show an aptitude for it. Cult expert Janja Lalich points out
      that leaders can use their emotional intelligence skills for ill in the same way
      they can for good. "Sometimes the only difference is [the leader's] intent," she
      says. And business leaders Carol Bartz, William George, Sidney Harman, and Andrea
      jung (of Autodesk, Medtronic, Harman International, and Avon respectively)
      describe situations in which emotional intelligence traits such as self-awareness
      and empathy have helped them and their companies perform at a higher level.

PMID- 14723175
TI  - Thinking about ... leadership. Warts and all.
AB  - Does using Tyco's funds to purchase a $6,000 shower curtain and a $15,000 dog
      shaped umbrella stand make Dennis Kozlowski a bad leader? Is Martha Stewart's
      career any less instructive because she may have sold some shares on the basis of
      a tip-off? Is leadership synonymous with moral leadership? Before 1970, the
      answer from most leadership theorists would certainly have been no. Look at
      Hitler, Stalin, Pol Pot, Mao Tsetung--great leaders all, but hardly good men. In
      fact, capricious, murderous, high-handed, corrupt, and evil leaders are effective
      and commonplace. Machiavelli celebrated them; the U.S. constitution built in
      safeguards against them. Everywhere, power goes hand in hand with corruption-
      everywhere, that is, except in the literature of business leadership. To read Tom
      Peters, Jay Conger, John Kotter, and most of their colleagues, leaders are, as
      Warren Bennis puts it, individuals who create shared meaning, have a distinctive
      voice, have the capacity to adapt, and have integrity. According to today's
      business literature, to be a leader is, by definition, to be benevolent. But
      leadership is not a moral concept, and it is high time we acknowledge that fact.
      We have as much to learn from those we would regard as bad examples as we do from
      the far fewer good examples we're presented with these days. Leaders are like the
      rest of us: trustworthy and deceitful, cowardly and brave, greedy and generous.
      To assume that all good leaders are good people is to be willfully blind to the
      reality of the human condition, and it severely limits our ability to become
      better leaders. Worse, it may cause senior executives to think that, because they
      are leaders, they are never deceitful, cowardly, or greedy. That way lies
      disaster.

PMID- 14723176
TI  - The seven ages of the leader.
AB  - Leaders go through many transitions in their careers. Each brings new crises and
      challenges--from taking over a damaged organization to having to fire somebody to
      passing the baton to the next generation. These moments can be wrenching--and can
      threaten your confidence--but they're also predictable. Knowing what to expect
      can help you get through and perhaps emerge stronger. In this engaging article,
      Warren G. Bennis, professor and founding chairman of the University of Southern
      California's Leadership Institute, reflects on leadership, recounting his own
      experiences as a young lieutenant in the infantry in World War II, as the new
      president of a university, and as the mentor to a unique nursing student. Bennis
      also describes the experiences of other leaders he has known throughout his
      career. Drawing on more than 50 years of academic research and business expertise
      -and borrowing from Shakespeare's seven ages of man--Bennis says the leader's
      life unfolds in seven stages. "The infant executive" seeks to recruit a mentor
      for guidance. "The schoolboy" must learn how to do the job in public, subjected
      to unsettling scrutiny of every word and act. "The lover with a woeful ballad"
      struggles with the tsunami of problems every organization presents. "The bearded
      soldier" must be willing--even eager--to hire people better than he is, because
      he knows that talented underlings can help him shine. "The general" must become
      adept at not simply allowing people to speak the truth but at actually being able
      to hear what they are saying. "The statesman" is hard at work preparing to pass
      on wisdom in the interests of the organization. And, finally, "the sage" embraces
      the role of mentor to young executives.

PMID- 14723177
TI  - When followers become toxic.
AB  - Leaders are vulnerable, too. That is, they can be led astray just as their
      followers can--actually, by their followers. This happens in a variety of ways.
      Sometimes, good leaders end up making poor decisions because well-meaning
      followers are united and persuasive about a course of action. This is a
      particular problem for leaders who attract and empower strong followers. These
      executives need to become more skeptical of the majority view and push followers
      to examine their opinions more closely. At other times, leaders get into trouble
      because they are surrounded by followers who fool them with flattery and isolate
      them from uncomfortable realities. Charismatic leaders, who are most susceptible
      to this problem, need to make an extra effort to unearth disagreement and to find
      followers who are not afraid to pose hard questions. Organizational mechanisms
      like 360-degree feedback and executive coaching can help these leaders get at the
      truth within their companies. Finally, unscrupulous and ambitious followers may
      end up encroaching on the authority of the leader to such an extent that the
      leader becomes little more than a figurehead who has responsibility but no power.
      There's not much leaders can do to completely guard against a determined
      corporate lago, but those who communicate and live by a positive set of values
      will find themselves better protected. And since followers tend to model
      themselves after their leaders, the straightforward leader is less likely to have
      manipulative followers. In this article, George Washington University professor
      Lynn Offermann explores each of these dynamics in depth, arguing that leaders
      need to stir debate, look for friends who can deliver bad news, and communicate
      and act on a solid set of values.

PMID- 14723178
TI  - Putting leaders on the couch. A conversation with Manfred F. R. Kets de Vries.
      Interview by Diane L. Coutu.
AB  - Much of the business literature on leadership starts with the assumption that
      leaders are rational beings. But irrationality is integral to human nature, and
      inner conflict often contributes to the drive to succeed. Although a number of
      business scholars have explored the psychology of executives, Manfred F.R Kets de
      Vries has made the analysis of CEOs his life's work. In this article, Kets de
      Vries, a psychoanalyst, author, and instead professor, draws on three decades of
      study to describe the psychological profile of successful CEOs. He explores
      senior executives' vulnerabilities, which are often intensified by followers'
      attempts to manipulate their leaders. Leaders, he says, have an uncanny ability
      to awaken transferential processes--in which people transfer the dynamics of past
      relationships onto present interactions--among their employees and even in
      themselves. These processes can present themselves in a number of ways, sometimes
      negatively. What's more, many top executives, being middle-aged, suffer from
      depression. Mid-life prompts a reappraisal of career identity, and by the time a
      leader is a CEO, an existential crisis is often imminent. This can happen with
      anyone, but the probability is higher with CEOs, and senior executives because so
      many have devoted themselves exclusively to work. Not all CEOs are
      psychologically unhealthy, of course. Healthy leaders are talented in self
      observation and self-analysis, Kets de Vries says. The best are highly motivated
      to spend time on self-reflection. Their lives are in balance, they can play, they
      are creative and inventive, and they have the capacity to be nonconformist.
      "Those who accept the madness in themselves may be the healthiest leaders of
      all," he concludes.

PMID- 14723179
TI  - Managers and leaders. Are they different? 1977.

PMID- 14723181
TI  - Understanding leadership. 1961.

PMID- 14723182
TI  - Atkins world.

PMID- 14723183
TI  - Peter Drucker sets us straight. Interview by Brent Schlender.

PMID- 14723184
TI  - Reality checkup. A growing amount of bad debt means earnings at hospital
      companies might not be as healthy as they appear.

PMID- 14723185
TI  - Memories of estrogen.

PMID- 14723186
TI  - In a hurry to slow life's clock.

PMID- 14723187
TI  - A market for wellness.

PMID- 14723189
TI  - As "back to sleep" becomes more common, so does the risk of flatter heads...and
      how to prevent them.

PMID- 14723188
TI  - Does infant diet increase the risk of diabetes?

PMID- 14723190
TI  - Two more reports link air pollution and asthma...and an editorial view.

PMID- 14723191
TI  - More benefits of fruits and vegetables?

PMID- 14723192
TI  - Resources. Managing serious food allergies in schools.

PMID- 14723194
TI  - Product recalls. Recalls: toy necklaces...and Simon & Schuster children's books.

PMID- 14723193
TI  - Resources. Parents' guide to immunization.

PMID- 14723195
TI  - Reevaluating your cholesterol.

PMID- 14723196
TI  - Easing fears about undergoing prostate biopsy.

PMID- 14723197
TI  - Tapping into the "real" fountain of youth.

PMID- 14723198
TI  - Same-day surgery: your step-by-step guide.

PMID- 14723199
TI  - My friend and I both had mammograms showing calcium deposits, but only one of us
      had a biopsy. Why?

PMID- 14723200
TI  - What is a megadose and why do you recommend against taking megadoses of vitamins?

PMID- 14723201
TI  - Do grilled food cause cancer?

PMID- 14723203
TI  - Assessing your risk of oral cancer.

PMID- 14723202
TI  - Who needs cardiac evaluation?

PMID- 14723204
TI  - Strategies for better asthma control.

PMID- 14723205
TI  - Stretching out the benefits of exercise.

PMID- 14723206
TI  - What can I do to improve my declining sense of taste?

PMID- 14723208
TI  - African regional follow-up to the World Conference against Racism.

PMID- 14723207
TI  - Why does my doctor want me to drink so much water?

PMID- 14723209
TI  - UN appoints a special rapporteur on the right to health.

PMID- 14723210
TI  - African regional meeting on HIV/AIDS and human rights.
AB  - A meeting of countries in the Southern African Development Community (SADC) leads
      to the establishment of a regional alliance of organizations working on HIV/AIDS
      and human rights.

PMID- 14723211
TI  - Nigeria health rights group provides legal support.

PMID- 14723212
TI  - Legislative initiatives in the Asia Pacific region.
AB  - This section reports on legislative developments in Australia, Papua New Guinea,
      and Cambodia.

PMID- 14723213
TI  - Malignant histories: Psychosomatic medicine and the female cancer patient in the
      postwar era.
AB  - Cancer had often been linked with unhappy emotions in the past, but this
      association entered a new phase in the middle of the 20th century as a result of
      research in the field of psychosomatic medicine conducted in the United States
      during the 1950s. There researchers focused particularly upon cancer in women,
      and were strongly influenced by the prevailing psychoanalytic orthodoxy
      surrounding the nature of femininity and normal female sexuality. The results of
      these studies, which appeared in the Journal Psychosomatic Medicine, confirmed
      the personality-cancer link out but were rife with erroneous assumptions and
      faulty methodologies. They were widely publicized, nonetheless, and were
      instrumental in promoting the association between repression and cancer,
      especially in women. Despite criticism, their influence was manifest in psycho
      oncological research in many countries during the decades which followed and
      popular notions of the "cancer personality."

PMID- 14723214
TI  - [How did U.S. Public Health System help American fight against SARS].

PMID- 14723215
TI  - [Consensus of the management of severe acute respiratory syndrome].

PMID- 14723216
TI  - Ileal pouchitis and arthritis.

PMID- 14723217
TI  - [Fluorescence technique on diagnosis of urinary bladder carcinoma].

PMID- 14723218
TI  - The oral brush biopsy: separating fact from fiction.

PMID- 14723219
TI  - Blood loss in orthognathic procedures--is there an indication to cross match?

PMID- 14723220
TI  - The aging forehead.

PMID- 14723221
TI  - Information technology at the Department of Nuclear Medicine.
AB  - The Department of Nuclear Medicine because of its scope does much more work with
      computers, data and communication technologies than other departments in the
      hospital. Finding an efficient and user-friendly way of collecting and handling
      data, presenting them to the rest of the hospital and storing them in archives is
      one of the important tasks currently being addressed. This article concentrates
      on a discussion of the features of data flow between the department and the
      hospital and the organization of data at the department. A possible solution of
      an information system dealing with text data and images is presented on the
      example of the Department of Nuclear Medicine-PET Centre located in the Na
      Homocle Hospital in Prague.

PMID- 14723222
TI  - Functional neuroimaging in language processing and aphasia.

PMID- 14723223
TI  - Sulphate metabolism of selenate-resistant Schizosaccharomyces pombe mutants.
AB  - Selenate-resistant mutants were obtained from several strains of
      Schizosaccharomyces pombe. The obtained mutants all belonged to the same genetic
      complementation group. They were low in sulphate uptake activity and in ATP
      sulphurylase activity. They grew on medium containing sulphite, thiosulphate,
      cysteine or glutathione but not methionine as the sole source of sulphur. From
      these results, the mutants were concluded to carry mutations in the ATP
      sulphurylase gene. Inability of the mutants to utilize methionine as a sulphur
      source is rationalized by the absence of the reverse transsulphurylation pathway
      in this organism; wild type strains must utilize methionine as a sulphur source
      after it is degraded to give rise to sulphate.

PMID- 14723224
TI  - End of the road for tamoxifen?

PMID- 14723225
TI  - New treatment hope for prostate cancer.

PMID- 14723226
TI  - Will you survive surgery for colorectal cancer?

PMID- 14723227
TI  - Women with breast cancer opt for treatment with minimal side-effects.

PMID- 14723228
TI  - Share with women. Get moving!

PMID- 14723229
TI  - Inheritance of microsatellite DNA markers in the Pacific abalone Haliotis discus
      hannai.
AB  - Microsatellite markers have been developed for a variety of abalones, and locus
      specific homozygote excesses at population level have been recorded for
      microsatellite loci. To ascertain whether null alleles exist at microsatellite
      loci in the Pacific abalone, we studied the mode of inheritance of 7
      microsatellite loci in 4 families with a reciprocal cross of 2 females x 2 males.
      All loci segregated codominantly, but only 3 loci ( Hdh1321, Hdh78, and Hdd108C)
      conformed to Mendelian segregation and can be used for parental analysis and
      population genetic studies. When null alleles were considered, 2 loci (Hdh1761
      and Hdh1457) confirmed Mendelian expectations in all families, while the
      remaining 2 loci (Hdd114B and Hdd229) showed deviation from Mendelian segregation
      in at least one family even though null alleles were considered. These results
      indicated the need to test the inheritance pattern for microsatellite markers in
      abalones before using them for population genetic of parentage analysis.

PMID- 14723230
TI  - Benefit of IVIg for long-standing ataxic sensory neuronopathy with Sjogren's
      syndrome.

PMID- 14723231
TI  - Space nursing:  expanding the horizons.

PMID- 14723232
TI  - Know thyself.

PMID- 14723233
TI  - [Periconceptional intake of a folic acid supplement: evaluation of a promotional
      program].
AB  - This study evaluates the efficacy of a regional program promoting
      periconceptional folic acid intake. Data were collected through a self
      administrated questionnaire among 721 (405 for phase I; 316 for phase II)
      primiparous women. For phase I, 26.1% (CI [Confidence Interval] 95%: 21.9%-30.4%)
      of respondents took an adequate periconceptional folic acid supplement, whereas
      this proportion was 31.6% (CI 95%: 26.5%-36.7%) for phase II (p>0.05). For phase
      I, 62.0% (CI 95%: 57.3%-66.7%) of women recognized the role of folic acid. For
      phase II, this proportion significantly rose to 70.9% (CI 95%: 65.9%-75.9%).
      Regional activities promoting periconceptional folic acid intake, if maintained,
      should be modified to significantly increase the proportion of women taking an
      adequate amount of folic acid.

PMID- 14723234
TI  - Time out of mind.

PMID- 14723235
TI  - "To see today with the eyes of tomorrow": A history of screening mammography.
AB  - Mammography represents an interesting chapter in the history of American medical
      technology. Throughout much of the 20th century, physicians showed little
      interesting in using x-rays to help diagnose breast cancer. But beginning in the
      1960s, with the growing interest in early detection, the professionalization of
      radiology and cancer activism, and the increasing allure of visual imagery in
      medicine, screening mammograms became the centerpiece of efforts to lower
      mortality from breast cancer. Despite its popularity, however, mammography
      remains highly controversial as physicians, statisticians and the public have
      continued to debate its actual clinical value. Mammography well exemplifies how
      cultural, ideological and political factors influence both the dissemination and
      evaluation of medical technologies.

PMID- 14723236
TI  - [Outbreak of the food poisoning due to contaminated low fat milk in Japan and the
      preventive measures].

PMID- 14723237
TI  - [Eradication of microbes by washing during food processing].

PMID- 14723239
TI  - [Food labeling].

PMID- 14723238
TI  - [The value of iron determination. Comment on Hermann Heimpel, Martin Riedel,
      Roman Wennauder, Lothar Thomas: Plasma iron determination--useful, unnecessary or
      misleading?].

PMID- 14723240
TI  - [Arcobacter].

PMID- 14723241
TI  - [Useful knowledge of the food hygiene and sanitation in our home page].

PMID- 14723242
TI  - Increasing false recognition rates with confirmatory feedback: a phenomenological
      analysis.
AB  - During a simulated witness interrogation, participants were encouraged to
      confabulate an account consistent with false information concerning a videotaped
      event. The interviewer verbally affirmed some false responses. Previous research
      has shown that, a week later, participants often recognize confabulated events
      that were affirmed by the experimenter as being from the video. What is unclear
      is whether confirmatory feedback encouraged a change in the mental representation
      of the confabulated events to fit the original event or confirmation might have
      merely encouraged a change in beliefs about the event. To further understand the
      mechanisms that underlie the confirmatory feedback effect, participants were
      asked to judge the phenomenological experience associated with false recognition.

PMID- 14723243
TI  - Recognition of odors and identification of sources.
AB  - The purpose of the present study was to investigate the accuracy of the memory
      for odors and for the location of odors. In Experiment 1, 5 unfamiliar odors were
      presented in each of 2 rooms. Twenty participants were instructed to remember
      only the odors (odor-only control group) and 20 were instructed to remember both
      the odors and the room where the odors were presented (odor place group). In
      Experiment 2, both the odor presentation room and the sex of the experimenters
      were manipulated to increase the uniqueness of the odor location. The results
      demonstrated that the memory for an odor is superior to the memory for the
      location of an odor. The results also indicated that the intention to learn the
      sources of an odor improves the memory for the source. These results are
      discussed in the context of the source monitoring framework.

PMID- 14723244
TI  - Multiple number and letter comparison: directionality and accessibility in
      numeric and alphabetic memories.
AB  - In 3 experiments, subjects made comparativejudgments on a set of 2 numbers or
      letters, 3 numbers or letters, or 5 numbers or letters. Numeric and alphabetic
      serial order memories were contrasted. Three aspects of serial order memory
      processes were identified: computational complexity, directionality, and
      accessibility. Computational complexity is the number of algorithmic steps
      involved in identifying a target. Directional bias is measured as the speed
      differences in identifying serial targets of equal computational complexity in a
      stimulus array. Memory accessibility is measured as the numeric and alphabetic
      serial position effects. Subjects had a slight directional bias favoring backward
      ordering for single digits but no bias in 2-digit number ordering, in contrast to
      a strong forward directional advantage in letter ordering. The speed of number
      access was found to steadily and evenly decrease along the numeric scale, in
      contrast to a systematic pattern of variations in alphabet access along the
      alphabetic scale. Finally, the middle item effect (the middle item in a multi
      item array is identified most slowly) found in Jou's (1997) multiple-letter
      comparison study was generalized to numbers.

PMID- 14723245
TI  - Judging the pleasantness of contour-rhythm-pitch-timbre musical combinations.
AB  - The way people with various degrees of musical training integrate timbre, melodic
      contour, rhythm, and pitch information in an overall pleasantness judgment for
      musical excerpts was investigated. The theoretical and methodological framework
      of the study was the functional theory of cognition. In 2 experiments,
      participants were asked to attribute an overall pleasantness value to
      combinations of these factors. In Experiment 1, timbre, contour, rhythm, and
      overall pitch were manipulated. In Experiment 2, timbre and theme (a pattern of
      pitch and rhythm) were manipulated. Both experiments showed that in judging the
      pleasantness of musical combinations, participants apply a simple, additive rule
      in which the weight attributed to one element does not depend of the value of the
      other elements. Very few differences in regard to the combination rule were
      observed between participants with and without musical training. These results
      are discussed in reference to the controversy over pitch and rhythm interaction.

PMID- 14723246
TI  - Rules and problem solving: another look.
AB  - College students were trained on problems similar to the water jar problems
      developed by Luchins (1942). Some students were instructed that a particular rule
      would solve all the problems, others had the same problems but were not
      instructed about the rule, and a third set of students had a series of novel
      problems in which no single rule operated throughout. In two experiments students
      in the instructed rule group not only performed best in training but also
      performed best when transferred to a condition in which a single novel rule was
      appropriate. Although results from the set of conditions most similar to those of
      Luchins suggested that students sometimes inappropriately persisted in rule
      usage, the overall results suggest that rigidity is not a necessary outcome of
      instructed problem solving. Indeed, many of the results were consistent with the
      notion that instructed problem solving is flexible problem solving.

PMID- 14723247
TI  - Effect of color on expected and experienced refreshment, intensity, and liking of
      beverages.
AB  - The effect of color on the expected and experienced refreshment, intensity, and
      liking of lemon, mint, and vanilla beverages was studied. Subjects rated the
      expected and actual taste of brown lemon and mint solutions as less refreshing
      than the tastes of differently colored solutions of the same flavor. However, the
      refreshment ratings (expected and actual) of the brown vanilla beverage were not
      different from those of the vanilla beverages of other colors. Liking ratings
      also depended on color in a manner similar to that of the refreshment ratings.
      Intensity ratings also varied with color. However, unlike when subjects smell
      solutions rather than taste them, colored solutions were not judged as more
      intense than colorless ones. In fact, the clear solutions were judged as
      strongest.

PMID- 14723248
TI  - Anne Anastasi (1908-2001).

PMID- 14723249
TI  - Virulence factors of Candida species.
AB  - Candida albicans is an opportunistic human pathogen, which colonizes at several
      anatomically distinct sites including skin, oral, gastrointestinal tract, and
      vagina. How harmless commensal C. albicans become a human pathogen when
      opportunity comes is not clear. This review will focus on the molecular
      dissection of virulence factors of C. albicans, including adhesion, proteinases
      secretion, hyphal formation, and phenotypic switching. This review will also
      describe briefly the virulence factors in non-albicans Candida spp.

PMID- 14723250
TI  - Intracellular proteins involved in Porphyromonas gingivalis-induced
      opsonophagocytic activities of a murine macrophage cell line (RAW264.7 cells).
AB  - The aim of this study was to determine the role of intracellular proteins in
      phagocytosis of opsonized Porphyromonas gingivalis by RAW264.7 cells, a murine
      macrophage-like cell line. This periodontopathogen was grown anaerobically and
      opsonized with an IgG2a murine monoclonal anti-P. gingivalis lipopolysaccharide
      antibody. RAW264.7 cells were preincubated with protein tyrosine kinase
      inhibitors (staurosporine and genistein), protein kinase C inhibitors (phorbol
      myristic acetate and bisindolylmaleimide), a serine/threonine phosphatase
      inhibitor (okadaic acid), a phosphatidylinositol 3-kinase inhibitor
      (worthmannin), phospholipase A2 inhibitors (bromophenacyl bromide and
      nordihydroguaiaretic acid), phospholipase C inhibitors (p-chloromercuriphenyl
      sulfonate and neomycin sulfate), an actin-filament depolymerizer (cytochalasin
      D), and a microtubule disrupting agent (colchicine). Inhibitor-treated
      macrophages were then incubated with the opsonized P. gingivalis and the
      phagocytosed cells determined microscopically. The results showed the percentage
      of the phagocytosed organisms decreased when the cells were preincubated with
      protein tyrosine kinase, protein kinase C, protein phosphatase and
      phosphatidylinositol 3-kinase inhibitors. Of interest, preincubation with phorbol
      myristic acetate for 30 min increased the ability of RAW264.7 cells to
      phagocytose the opsonized organisms. Phospholipase A2 and phospholipase C
      inhibitors only slightly reduced the number of phagocytosed organisms. The
      results indicated that opsonophagocytosis of P. gingivalis by RAW264.7 cells
      might be determined by the activation of protein tyrosine kinase, protein kinase
      C, protein phosphatases, and phosphatidylinositol 3-kinase inhibitor. Both
      phospholipase A2 and phospholipase C would appear to be involved to a lesser
      extent. The opsonophagocytosis of this periodontopathogen would also appear to be
      dependent upon actin and microtubule polymerization.

PMID- 14723251
TI  - Effectiveness of Dp2 nasal therapy for Dp2- induced airway inflammation in mice:
      using oral Ganoderma lucidum as an immunomodulator.
AB  - Nasal immunotherapy with allergen has been reported to be effective for airway
      allergic disease. A group of 50 male Balb/c mice were immunized intraperitoneally
      with recombinant Dermatophagoides pteronyssinus group 2 (rDp2), then oral feeding
      with Ganoderma lucidum (known as "Ling Zhi," LZ OT) and intranasal therapy with
      native Dp2 (Dp2 NT) were given, the mice then received intratracheal challenge
      with rDp2 at 28 days and 35 days after immunization. Airway hypersensitivity to
      methacholine was measured 30 min (early phase) and 24 h (late phase) after the
      second challenge. The cytokine producing CD4 cells in PBL and interferon-gamma
      (IFN-gamma) concentrations in bronchoalveolar lavage fluid and sera were measured
      on 37 days after immunization. Both Dp2 NT and LZ OT downregulated total
      inflammatory cell infiltration in the airway. Dp2 NT reduced IL-5+/CD4+ cells and
      increased IFN-gamma+/CD4+ cells. When LZ OT was added to Dp2 NT, the reduction of
      IL-5+/CD4+ cells was diminished and the increment of IFN-gamma+/CD4+ cells was
      increased. LZ OT alone increased both IL-5+/CD4+ cells and IFN-gamma+/CD4+ cells.
      When LZ OT was added to Dp2 NT, IgG2a was further increased to a significant
      level. LZ OT alone significantly suppressed IgG1 and increased IgG2a production.
      When lung function was measured after therapy, early phase airway
      hypersensitivity to methacholine significantly suppressed by Dp2 NT, while late
      phase hypersensitivity was suppressed but not to a significant level. When LZ OT
      was added to Dp2 NT, the suppression of late phase airway hypersensitivity to
      methacholine reached a significant level. In this mouse model of Dp2-induced
      airway hypersensitivity, Dp2 NT downregulated airway inflammatory cell
      infiltration and decreased immediate airway hypersensitivity to methacholine.
      When LZ OT was coadministered, the airway lymphocytes and circulatory IFN
      gamma+/CD4+ were both increased and late phase airway hypersensitivity was
      decreased. These results suggest that Dp2 NT might have a therapeutic effect on
      Dp2-induced airway hypersensitivity and LZ OT might also have an effect on Dp2 NT
      immunotherapy.

PMID- 14723252
TI  - Fever of unknown origin: a retrospective study of 78 adult patients in Taiwan.
AB  - To elucidate the causes of fever of unknown origin (FUO) in Taiwan, we
      retrospectively analyzed the characteristics of 78 adult patients meeting the
      classic criteria for fever of unknown origin who were treated at National Taiwan
      University Hospital from July 1999 through June 2002. Cause of FUO was due to
      infections in 42.3% of patients, neoplasms in 6.4%, noninfectious inflammatory
      diseases in 20.5%, and miscellaneous causes in 7.7%, whereas the cause was not
      established in 23.1% of patients despite every effort. Tuberculosis (14.1%) and
      acquired immunodeficiency syndrome (7.7%) were the most common causes of
      infection in patients with FUO, while intraabdominal abscess, infective
      endocarditis, and tumor were less frequently found. Noninfectious inflammatory
      diseases were still a very important cause of FUO and were difficult to diagnose.
      In conclusion, infection remains the most important cause of classic FUO in
      Taiwan, confirming the findings in previous series. The importance of
      tuberculosis and AIDS as frequent causes of FUO should be emphasized.

PMID- 14723253
TI  - Mycobacteriosis in patients with fever of unknown origin.
AB  - Fever of unknown origin (FUO) is a common syndrome. A total of 94 patients (57
      men and 37 women; mean age, 56.3 +/- 19 years, range, 18-86 years) who met the
      criteria of FUO were included in this study. Mycobacteriosis was diagnosed in 22
      (23%) of these patients (13 men and 9 women), including 9 with disseminated
      disease and 13 with pulmonary disease. There was no significant statistical
      difference in age, sex, short-term survival status (3 months), and other clinical
      parameters between patients with and without mycobacteriosis. Clinical
      manifestations may be specific or nonspecific. The most common initial
      presentations in patients with mycobacteriosis were respiratory tract symptoms,
      mainly of cough and dyspnea, observed in 11 (50%) patients, and disturbance of
      consciousness in 6 (27%). The associated conditions included malnutrition (4
      patients, 18%), diabetes mellitus (3, 14%), and renal failure (3, 14%). Four
      (18%) patients had a history of pulmonary tuberculosis or tuberculous spondylitis
      in their early adulthood. The 2 most common findings on chest radiograph were
      interstitial (41%) and nonspecific infiltrative (32%) patterns. In conclusion,
      mycobacteriosis remains the leading cause of FUO in southern Taiwan and it is
      important to screen for this treatable disease in all cases of FUO.

PMID- 14723254
TI  - Monotherapy with meropenem versus combination therapy with ceftazidime plus
      amikacin as empirical therapy for neutropenic fever in children with malignancy.
AB  - Fifty-four pediatric cancer patients with a total of 100 febrile neutropenic
      episodes treated at China Medical College Hospital were randomized to receive
      meropenem or ceftazidime plus amikacin from January 2001 to April 2002. The
      characteristics of 76 assessable febrile episodes (39 with meropenem and 37 with
      ceftazidime plus amikacin) were compared between the 2 groups. The success rate
      with unmodified therapy was not significantly different between the meropenem
      group (72%) and the ceftazidime-plus-amikacin group (57%). The incidence of side
      effects was similar between the 2 groups and these side effects were reversible.
      Microbiologically documented infection, clinically documented infection, and
      unexplained fever accounted for 35%, 37%, and 28% of episodes, respectively. The
      clinical response rates in subgroups of documented infection and unexplained
      fever did not significantly differ between the 2 treatment groups. Meropenem was
      significantly more effective than ceftazidime plus amikacin in children at high
      risks of developing severe infection who had profound neutropenia (absolute
      neutrophil count [ANC] < 100/mm3), prolonged neutropenia (ANC < 500/mm3 lasting
      for > 10 days), or clinically deteriorating shock (p=0.045). As an empirical
      treatment, meropenem seems to be as effective and safe as ceftazidime plus
      amikacin for febrile episodes in children with cancer and neutropenia. Meropenem
      is more effective for pediatric cancer patients at the high risk of severe
      infection.

PMID- 14723255
TI  - Acute hematogenous osteomyelitis and septic arthritis in children.
AB  - This retrospective study analyzed the clinical, bacteriological, and radiological
      features of pediatric patients with acute hematogenous osteomyelitis and septic
      arthritis. Eighty-four patients with septic arthritis and 39 with acute
      hematogenous osteomyelitis were enrolled. Their age ranged from 13 days to 17
      years. In patients with septic arthritis, the hip joint was the most often
      infected site. The tibia was the most often involved site in acute hematogenous
      osteomyelitis. A bacteriological diagnosis was established in 78 (63%) patients.
      Overall, methicillin-susceptible Staphylococcus aureus (36 cases) was the most
      common causative organism identified, followed by methicillin-resistant S. aureus
      (10 cases). The median duration of antibiotic therapy was 33 days. Serum
      bactericidal titers were obtained for 19 (15%) of the 123 patients. The median
      duration of hospitalization and antibiotic treatment was not significantly
      different between patients with and without serum bactericidal titer testing.
      More patients without serum bactericidal titer testing had symptom relapse which
      required re-admission for further treatment. In conclusion, the incidence of
      methicillin-resistant S. aureus as a cause of bone and joint infections has been
      increasing. Serum bactericidal titer is valuable for the management of patients
      receiving sequential therapy for acute hematogenous osteomyelitis and septic
      arthritis.

PMID- 14723256
TI  - Rhinocerebral mucormycosis in Taiwan.
AB  - To understand the demographic as well as clinical characteristics, and outcomes
      of patients with rhinocerebral mucormycosis in Taiwan, we retrospectively
      analyzed patients with this disease admitted to Chang Gung Memorial Hospital
      Kaohsiung from 1988 through 2000. The 21 patients included 8 men (28%) and 13
      women (62%). The median age was 60 years (range, 34-82 years). Twenty patients
      (95%) had underlying diabetes mellitus. The most common clinical feature at
      admission was ocular lesions, followed by headache, nostril lesions, and
      consciousness disturbance. Fifteen (94%) of 16 patients who received combined
      surgical debridement and therapy with amphotericin B survived, while only 1 (20%)
      of the 5 patients who received amphotericin B alone survived (p=0.004). The
      diagnosis of rhinocerebral mucormycosis was delayed in 4 patients (19%). Of the
      16 patients who survived, 1 (6%) had delayed diagnosis, while of the 5 patients
      who died, 3 (60%) had delayed diagnoses (p=0.028). This series disclosed a higher
      proportion of patients with rhinocerebral mucormycosis in Taiwan had underlying
      diabetes mellitus, and ocular lesions were more frequent than nostril lesions at
      the time of admission. These results highlight the importance of the timely
      initiation of a combination of aggressive surgical debridement and treatment with
      amphotericin B in patients with rhinocerebral mucormycosis. Considering the high
      rate of delayed diagnosis, improved clinician's awareness of mucormycosis is
      extremely important and is in urgent need in Taiwan.

PMID- 14723257
TI  - Clinical manifestations of parainfluenza infection in children.
AB  - Parainfluenza viruses are major pathogens causing respiratory illness,
      manifesting from mild upper respiratory tract infection to bronchiolitis and
      pneumonia. This retrospective study aimed at providing clinical and epidemiologic
      data addressing the parainfluenza virus infection in Taiwan. A total of 39
      patients were enrolled in this study from March 1999 to December 2000. Infants
      and young children were the major susceptible population, with 87.2% of them
      younger than 3 years. No seasonal trend was noted for parainfluenza type 1 and
      type 2 infections. One clustering of parainfluenza virus type 3 infections
      occurred in late spring of 2000 based on collected results. Parainfluenza type 1
      viral isolates accounted for all of the cases of croup. Most isolates of
      parainfluenza virus type 3 were associated with upper and/or lower respiratory
      tract infections. A substantial proportion of the patients had skin involvement;
      the identification of one case of possible parainfluenza virus-related erythema
      multiforme is particularly interesting, especially because the chances of a
      causal relation between viral infection and skin symptoms are formerly thought to
      be slight. The identification of parainfluenza virus in illnesses classically
      considered to be due to other viruses is intriguing and may have important
      implications in the management of childhood illness clinically.

PMID- 14723258
TI  - Clinical observation between chronic sustained cough with asthma and childhood
      inguinal hernia.
AB  - Inguinal hernias are common and cause problems for the health services. Several
      factors are thought to influence their development. Patients under 16 years old
      who had received hernioplasty at National Taiwan University Hospital were
      enrolled in a study to analyze the correlation between preceding recurrent cough
      with asthma and later hernia development. Patients aged 5 and 6 years old (when
      admitted for hernioplasty in 2000) were particularly focused. This entailed
      further analysis of their birth history, family atopic history, specific allergic
      diseases (allergic rhinitis, atopic dermatitis, asthma), hernia type (direct or
      indirect), the onset of chronic cough and asthma. One hundred and sixty three
      patients (2.66%) from a total hernioplasty population of 6130 were found to have
      had preceding asthma with recurrent cough before having the hernioplasty
      intervention. One hundred twenty-five patients were aged 5 to 6 years old, among
      whom 8 (6.4%) patients were found to have asthma, and 20 (16%) patients were
      noted to have recurrent sustained cough. All the hernia types were indirect and
      were received with high suture ligation. In conclusion, the incidence of asthma
      was not significantly higher in the group of individuals receiving hernioplasty.
      However, a higher incidence of recurrent sustained cough was noted, which could
      be a relatively important factor for the hernia development. Further reliable
      cough measurements would be needed to evaluate the severity of recurrent
      sustained cough as the potential risk for the hernia development.

PMID- 14723259
TI  - Methimazole-induced lupus erythematosus: a case report.
AB  - A 15-year-old girl had a history of diffuse goiter and received methimazole
      treatment 2 months before admission to the hospital. She developed bilateral
      lower leg edema 5 days before admission and the laboratory examinations revealed
      leukopenia, anemia, proteinuria, and granular cast. Positive antinuclear
      antibodies and anti-double strand (anti-ds) DNA antibodies were noted, although
      complement levels were not reduced. Myeloperoxidase antineutrophil cytoplasmic
      antibody was positive. A renal biopsy disclosed that there was focal segmental
      glomerulosclerosis. Methimazole was discontinued, and she was treated with
      prednisolone and Plaquenil, after which the symptoms and laboratory tests became
      normal within 40 days. The prednisolone was discontinued after treatment for
      seven months. Currently, the anti-dsDNA, C3, C4, CBC, urinalysis, and thyroid
      function tests are within normal limits. With hydroxychloroquine and
      levothyroxine, she was free of symptoms after discontinuation of methimazole
      until now (about 21 months).

PMID- 14723260
TI  - Brain abscess caused by Salmonella enterica subspecies houtenae in a patient with
      chronic granulomatous disease.
AB  - A 44-month-old boy with chronic granulomatous disease has been suffering from
      fever and skin rash for 7 days prior to admission. The blood culture obtained on
      admission revealed Salmonella enterica subspecies houtenae. He received
      intravenous ceftriaxone therapy during his hospital stay and oral cefixime after
      discharge. Unfortunately, the same symptoms recurred 2 weeks after discontinuing
      cefixime and the culture from the aspirate of a skin nodule yielded the same
      microorganism again. He received intravenous ceftriaxone therapy after
      readmission and became afebrile 3 days later. However, focal seizure was noted on
      the 14th day of hospitalization. Brain magnetic resonance imaging revealed
      multiple brain abscesses, and electroencephalogram showed epileptiform activity.
      The intravenous antimicrobial agents were continued for a total of 84 days and
      interferon-gamma was administered as adjunctive therapy. Finally, he recovered
      from brain abscesses without any neurologic sequel. It is suggested that an
      extended course of antimicrobial treatment is necessary for chronic granulomatous
      disease with pyogenic infection because of the defective intracellular killing
      ability.

PMID- 14723261
TI  - Acute acalculous cholecystitis and pancreatitis in a patient with concomitant
      leptospirosis and scrub typhus.
AB  - Concomitant leptospirosis and scrub typhus is rare. The spectrum of clinical
      severity for both scrub typhus and leptospirosis ranges from mild to fatal. Acute
      pancreatitis and cholecystitis are infrequent complications in adult patients
      with either leptospirosis or scrub typhus. We report a case of leptospirosis and
      scrub typhus coinfection in a 41-year-old man presenting with acute acalculous
      cholecystitis, pancreatitis and acute renal failure. Abdominal computed
      tomography revealed edematous change of the gallbladder without intrahepatic or
      pancreatic lesions. The patient was successfully treated with doxycycline and
      ceftriaxone, and supportive management.

PMID- 14723262
TI  - Suitability of the traditional microbial indicators and their enumerating methods
      in the assessment of fecal pollution of subtropical freshwater environments.
AB  - Twenty-four freshwater sampling sites (11 river water, 6 spring water, and 7
      groundwater) were selected from 4 sampling areas located in the northern and
      central parts of Taiwan. A total of 125 water samples were collected during a 5
      month sampling period, and the numbers of total heterotrophic bacteria, total
      coliforms, fecal coliforms, enterococci, Aeromonas hydrophila, and Salmonella
      spp. were enumerated. Besides the traditional membrane filtration method, total
      coliforms and Escherichia coli were also simultaneously enumerated using the
      Colilert (Quanti-Tray/2000) method. On average, 94% and 80% of the water samples
      assessed with the Colilert method had equal or higher total coliform and E. coli
      counts, respectively, as compared with the membrane filtration method.
      Furthermore, when m-FC agar was used to enumerate fecal coliforms, 18% of the
      samples failed to yield the typical bluish colonies, while E. coli were counted
      in the same samples using the Colilert method. The data indicate that the m-FC
      agar culture method is inadequate for the enumeration of fecal coliforms in
      subtropical water samples. Significant correlations were observed between the
      total number of bacteria and various indicator bacteria in river water samples,
      but no such correlations were found for groundwater and spring water. This
      finding suggested that the river water was polluted by anthropogenic sources. The
      counts of total coliforms, E. coli, and other indicator bacteria were
      significantly correlated in all river water samples, while in groundwater and
      spring water, significant (p<0.01) correlation was only observed with
      enterococcal counts. The presence of total coliforms/E. coli generally implies
      the presence of fecal pollution possibly including pathogenic enteric bacteria.
      However, no Salmonella spp. were detected in any of the 107 water samples
      analyzed. The results of this study suggest that the use of these commonly
      employed microbial indicators for assessing subtropical water quality, especially
      in a pristine body of water (ie, mountain spring and groundwater), is highly
      questionable.

PMID- 14723263
TI  - Technetium-99m sestamibi single photon emission computed tomography findings
      correlated with P-glycoprotein expression, encoded by the multidrug resistance
      gene-1 messenger ribonucleic acid, in intracranial meningiomas.
AB  - The present study evaluated whether technetium-99m sestamibi (99mTc-MIBI) single
      photon emission computed tomography (SPECT) characteristics of intracranial
      meningioma are correlated with the histological malignancy, proliferative
      potential, and P-glycoprotein (Pgp) expression, encoded by the multidrug
      resistance gene-1 (MDR-1) messenger ribonucleic acid (mRNA). Twenty-one patients
      with intracranial meningiomas, including 17 benign and four nonbenign
      meningiomas, underwent 99mTc-MIBI SPECT imaging at 15 minutes (early) and 3 hours
      (delayed) after injection. The tumor-to-normal pituitary gland ratio was
      calculated on both early (ER) and delayed (DR) images. Retention index (RI) was
      calculated using the following formula: (DR - ER)/ER x 100%. Meningioma specimens
      were examined by immunohistochemistry using anti-Pgp and MIB-1 monoclonal
      antibody. MDR-1 mRNA expression was also investigated using reverse transcription
      polymerase chain reaction assay. 99mTc-MIBI was highly accumulated and retained
      in the tumors. 99mTc-MIBI SPECT findings were not related to MIB-1 labeling
      index. 99mTc-MIBI SPECT RI of the Pgp-positive group (-9.12 +/- 22.27%) was
      significantly lower than that of the Pgp-negative group (28.79 +/- 22.80%) (p =
      0.0016). No significant difference was seen in ER and DR between the positive and
      negative groups. These results show that 99mTc-MIBI may not be useful for
      determining proliferative potential and histological malignancy, but could
      predict anticancer drug resistance related to the expression of MDR-1 mRNA and
      its gene product Pgp in patients with intracranial meningiomas.

PMID- 14723264
TI  - Neuroendoscopic septostomy for isolated lateral ventricle.
AB  - The clinical features and endoscopic findings were investigated in 20 patients
      with isolated lateral ventricle treated by neuroendoscopic septostomy to
      establish cerebrospinal fluid communication and open an isolated ventricular
      compartment. The endoscopic procedure was incomplete because of thickened septum
      pellucidum and insufficient working space in two adults with postmeningitic
      hydrocephalus. Two children underwent second septostomy. In all other cases,
      results were good and there were no complications related to endoscopic
      procedures. Endoscopic septostomy is less invasive and has few complications.
      Intraoperative navigation and the biportal approach may be required in difficult
      cases with multiple septum formation and severe postmeningitic hydrocephalus.
      Adequate stomal size is required in high-risk groups including children under 2
      years of age.

PMID- 14723265
TI  - Postoperative seizures: epidemiology, pathology, and prophylaxis.
AB  - The risk of epileptic seizures after craniotomy is extremely important but the
      incidence of postoperative epilepsy varies greatly, depending on the patient's
      conditions such as primary diseases, severity of surgical insult, and pre
      existing epilepsy. Animal studies suggest that neurosurgical insults lead to
      seizures by two different mechanisms: One mechanism is mediated by free radical
      generation and the other by impaired ion balance across the cell membrane caused
      by ischemia or hypoxia. Conventional antiepileptic agents such as phenytoin,
      phenobarbital, carbamazepine, and valproic acid are promising for the prevention
      of early seizures, but the effect in preventing postoperative epilepsy is still
      controversial. Studies on the prophylactic effect of newer antiepileptic agents
      in craniotomized patients were very limited. Zonisamide, an antiepileptic agent
      with antiepileptogenic, free radical scavenging and neuroprotective actions in
      experimental animals, showed promising effects against postoperative epilepsy in
      a randomized double blind controlled trial. Prophylactic treatment for
      craniotomized patients significantly prevented the development of partial
      seizures during the follow-up period. Most recent studies have not supported the
      prophylactic use of antiepileptic agents in craniotomized patients, but further
      studies are required.

PMID- 14723267
TI  - Subarachnoid hemorrhage associated with clival chordoma--case report.
AB  - A 66-year-old man presented with clival chordoma associated with subarachnoid
      hemorrhage. Computed tomography showed subarachnoid hemorrhage in the right
      ambient cistern and a well-enhanced tumor in the petroclival region. Surgical
      exploration performed on the day of admission showed a clot in the tumor. The
      tumor was totally removed. Histological examination showed hemorrhage between the
      tumor and the dura. The diagnosis was clival chordoma. Subarachnoid hemorrhage in
      chordoma seems to occur by spreading of intratumoral hemorrhage into the
      subarachnoid space due to dural invasion.

PMID- 14723266
TI  - Ruptured aneurysm of the medial posterior choroidal artery first demonstrated by
      the microcatheter technique--case report.
AB  - A 50-year-old previously healthy woman presented with symptoms of subarachnoid
      hemorrhage. Initial cerebral angiography did not determine the site of the
      hemorrhage but repeat angiography disclosed an aneurysm-like image, probably in
      the medial posterior choroidal artery (PChA). Selective angiography performed
      using a microcatheter technique clearly revealed two medial PChAs arising from
      the ambient segment of the posterior cerebral artery. One medial PChA included an
      aneurysm on the cisternal segment, then ran peripherally to supply the plexus in
      the roof of the third ventricle. The other medial PChA mainly supplied the pineal
      body, tegmentum of the midbrain, and posterior border of the thalamus. The
      patient underwent open surgery following the zygomatic approach and the parent
      artery was clipped. She was discharged without neurological deficits or
      compromise of higher brain functions.

PMID- 14723268
TI  - Fatal bleeding from arterial dissection after clipping of a ruptured aneurysm-
      case report.
AB  - A 67-year-old man died of subarachnoid hemorrhage (SAH) resulting from dissection
      of the distal part of the anterior cerebral artery (ACA). A saccular aneurysm in
      the anterior communicating artery had ruptured and was successfully clipped on
      Day 0. The patient recovered consciousness after surgery but his condition
      deteriorated due to another SAH on Day 1. A second surgical procedure disclosed
      bleeding from a laceration in the opposite wall of the ACA distal to the clipped
      aneurysm. Histological examination of the autopsy specimens revealed damage to
      the internal elastic lamina and inflammatory infiltration of leukocytes. The
      fatal dissection may have resulted from atherosclerosis, hemodynamic stress
      caused by hypertension, or trauma due to surgical manipulation.

PMID- 14723269
TI  - Intramedullary spinal cord metastasis: a rare and devastating complication of
      cancer--two case reports.
AB  - Two cases of very rare intramedullary spinal cord metastasis from colon carcinoma
      and renal carcinoma were treated primarily by microsurgical excision. A 44-year
      old female presented with colon carcinoma metastasis manifesting as complete
      neurological deficit. She had undergone colon resection 2 years previously for
      colon carcinoma. The tumor was excised by microsurgery with megadose steroid
      therapy but she remained paraplegic. A 43-year-old man presented with renal
      carcinoma metastasis manifesting as incomplete neurological deficits. He had
      undergone nephrectomy one year previously for renal carcinoma. The tumor was
      removed by microsurgery. He made a remarkable neurological recovery and became
      ambulatory after physical therapy.

PMID- 14723270
TI  - Subependymal giant cell astrocytoma with positive tuberin expression--case
      report.
AB  - An 11-year-old male presented with subependymal giant cell astrocytoma (SEGA)
      without other manifestations of tuberous sclerosis such as facial angiofibroma,
      epilepsy, or mental retardation. The diagnosis was "possible tuberous sclerosis
      complex" (TSC). Total resection of the tumor was performed. Immunohistochemical
      study revealed positive tuberin expression. In general, loss of tuberin is
      thought to be critical to the TSC phenotype. Our case demonstrated clear
      expression of tuberin in the SEGA specimen.

PMID- 14723271
TI  - Neurocutaneous melanosis associated with malignant leptomeningeal melanoma in an
      adult: clinical significance of 5-S-cysteinyldopa in the cerebrospinal fluid--
      case report.
AB  - A 35-year-old male presented with a variant of neurocutaneous melanosis with
      leptomeningeal malignant melanoma. He had three pigmented nevi from birth. He
      suffered diplopia followed by headache. T1-weighted magnetic resonance (MR)
      imaging revealed hydrocephalus and a small linear hyperintense lesion in the
      right frontal cortex. Several parts of the cortical sulci and the brain surface
      were slightly enhanced by gadolinium. Ventriculoperitoneal shunting was performed
      and extensive pigmented leptomeninges were recognized. Open biopsy established
      the diagnosis of leptomeningeal malignant melanoma. Combined chemoimmunotherapy
      was repeated every other month with monitoring of the 5-S-cysteinyldopa (5-S-CD)
      level in the cerebrospinal fluid (CSF). The 5-S-CD level decreased after each
      treatment, but the basal level steadily increased prior to the next treatment.
      Two years after the onset, he showed paraplegia caused by an extramedullary mass
      at the T-6 level. MR imaging showed that melanoma had involved the entire
      subarachnoid space including the whole spine. He underwent emergent removal of
      the spinal tumor and showed transient marked improvement. Further intensive
      chemotherapy was given. However, he died 31 months after the onset of massive
      proliferation of intracranial leptomeningeal melanoma. Measurement of CSF 5-S-CD
      levels is valuable for evaluating the therapeutic efficacy and for monitoring the
      progression of melanoma.

PMID- 14723272
TI  - Spontaneous cerebrospinal fluid rhinorrhea as a presenting symptom of aqueductal
      stenosis--case report.
AB  - A 30-year-old male patient presented with chronic spontaneous cerebrospinal fluid
      (CSF) rhinorrhea. He had sustained a mild head injury in childhood. Magnetic
      resonance imaging of the brain showed aqueductal stenosis associated with
      moderate supratentorial hydrocephalus, and erosion of the cribriform plate.
      Following insertion of ventriculoperitoneal shunt, the CSF rhinorrhea completely
      ceased and no direct repair of the CSF fistula was necessary. Long-standing
      spontaneous CSF rhinorrhea indicates the possibility of concurrent intracranial
      pathology, such as aqueductal stenosis.

PMID- 14723273
TI  - The development of executive function in early childhood.
AB  - According to the Cognitive Complexity and Control (CCC) theory, the development
      of executive function can be understood in terms of age-related increases in the
      maximum complexity of the rules children can formulate and use when solving
      problems. This Monograph describes four studies (9 experiments) designed to test
      hypotheses derived from the CCC theory and from alternative theoretical
      perspectives on the development of executive function (memory accounts,
      inhibition accounts, and redescription accounts). Each study employed a version
      of the Dimensional Change Card Sort (DCCS), in which children are required first
      to sort cards by one pair of rules (e.g., color rules: "If red then here, if blue
      then there"), and then sort the same cards by another, incompatible pair of rules
      (e.g., shape rules). Study 1 found that although most 3- to 4-year-olds failed
      the standard version of this task (i.e., they perseverated on the preswitch rules
      during the postswitch phase), they usually performed well when they were required
      to use four rules (including bidimensional rules) and those rules were not in
      conflict (i.e., they did not require children to respond in two different ways to
      the same test card). These findings indicate that children's perseveration cannot
      be attributed in a straightforward fashion to limitations in children's memory
      capacity. Study 2 examined the circumstances in which children can use
      conflicting rules. Three experiments demonstrated effects of rule dimensionality
      (uni- vs. bidimensional rules) but no effects of stimulus characteristics (1 vs.
      2 test cards; spatially integrated vs. separated stimuli). Taken together, these
      studies suggest that conflict among rules is a key determinant of difficulty, but
      that conflict interacts with dimensionality. Study 3 examined what types of
      conflict pose problems for 3- to 4-year-olds by comparing performance on
      standard, Partial Change, and Total Change versions of the DCCS. Results revealed
      effects of conflict at the level of specific rules (e.g., "If red, then there"),
      rather than specific stimulus configurations or dimensions per se, indicating
      that activation of the preswitch rules persists into the postswitch phase. Study
      4 examined whether negative priming also contributes to difficulty on the DCCS.
      Two experiments suggested that the active selection of preswitch rules against a
      competing alternative results in the lasting suppression of the alternative.
      Taken together, the results of these studies provide the basis for a revision of
      the CCC theory (CCC-r) that specifies more clearly the circumstances in which
      children will have difficulty using rules at various levels of complexity,
      provides a more detailed account of how to determine the complexity of rules
      required in a task, takes account of both the activation and inhibition of rules
      as a function of experience, and highlights the importance of taking
      intentionality seriously in the study of executive function.

PMID- 14723274
TI  - Executive function in context: development, measurement, theory, and experience.

PMID- 14723275
TI  - Adsorption of arsenic on flyash.
AB  - Studies on removal of AS(III) by adsorption on flyash and activated carbon powder
      have been carried out at room temperature (30 +/- 1 degrees C). The adsorption
      isotherm of AS(III) on flyash and activated carbon powder was obtained in a batch
      reactor. Various parameters such as pH, initial concentraction of adsorbate and
      absorbent dose were studied. The experimental adsorption data fitted reasonably
      well to the Langmuir and Freunlich isotherms for both the adsorbents. Activated
      carbon has been observed to have greater adsorptive capacity than flyash.

PMID- 14723276
TI  - Major ion correlation in groundwater of Kancheepuram Region, South India.
AB  - Groundwater samples were collected from both dugwells and borewells in an
      intensively irrigated area of Kancheepuram Taluk, Tamil Nadu. pH, EC and TDS of
      groundwater samples were measured in the site. The collected samples were
      analysed in the laboratory for Ca, Mg, Na, K, Cl, HCO3, CO3, SO4, NO3, P-PO4 and
      Si-SiO2. The results are used for inter elemental correlation analysis which
      indicates that most of the elements having good correlation. Piper Trilinear
      diagram is used to find out the hydrochemical type of groundwater which shows
      that most of them are CaHCO3 and the remaining are CaMgCl type. Hydrochemical
      characteristics of groundwater indicate that silicate weathering reaction is a
      probable source for high concentration of major ions.

PMID- 14723277
TI  - Cathodic protection system for underground M.S. pipeline of watersupply project.
AB  - Corrosion of steel embedded in soil can generally be explained in terms of long
      cell action arising from differential aeration. The significant factors to
      promote corrosion are soil potential, Resistivity and draining characteristics.
      As the corrosive nature of soil is not fixed absolute value, the said study can
      be analyzed by adopting the following methodology. i) Study of state of soil at
      different location. ii) Nature of corrosion under consideration With above
      methodology an attempt can be made to achieve the following objective to, i)
      Assess the extent of corrosive tendencies of soil along the pipeline. ii) Co
      relate potential and resistivity with corrosive parameters of soil and, iii)
      Suggest the appropriate remedial means for protecting it from corrosion. i.e.
      Galvanic activity.

PMID- 14723278
TI  - The study of temporal and spatial trends of water qulity of river Kshipra using
      water quality index.
AB  - Water quality index (WQI) plays an important role in interpreting the information
      on water quality trends of a water body. In the present study, an attempt has
      been made to study the spatial and temporal water quality trends of one of the
      pristine river Kshipra (Madhya Pradesh) using water quality index. The importance
      of existing sampling sites has also been discussed.

PMID- 14723279
TI  - Spent ion exchange resin-its treatment from the point of view of safe disposal.
AB  - Ion exchange process is one of the treatment methods for radioactive waste. The
      resin becomes no longer useful after number of cycles of usage. At the same time
      the regenerated resin cannot be considered as non active waste for disposal.
      Hence it is felt necessary that the regenerated resin is treated in a fashion so
      as to result in a form which can be considered as inactive material. It is
      possible to convert this spent resin into multivalent ionic form which are
      generally non leachable, thus providing the necessary properties for meeting the
      disposal criteria. Studies were carried out for the exchange of radioactive ions
      on these resins with ions like Al3+, Sn4+, Pb2+ and Fe3+ etc. The studies
      included leachability aspects, exchange with other active ions, thermal
      characteristics, compressive strength of the cement blocks loaded with the resin
      etc. Our studies indicated that the order of the stability of the resin with
      respect to properties like leachability, exchange properties etc. follow the
      trend as follows: Sn4+ > Pb2+ > Al3+ > Fe3+.

PMID- 14723280
TI  - Spectrophotometric studies on the investigation of chromium in environmental
      samples.
AB  - Isothipendyl hydrochloride is proposed as a sensitive and selective reagent for
      the rapid spectrophotometric determination of chromium(VI). The reagent
      instantaneously gives a red coloured species on reaction with chromium(VI) in
      phosphoric acid medium which exhibits maximum absorbance at 510 nm with Sandell's
      sensitivity of 2.28 ng cm(-2). Beer's law is valid over the concentraction range
      of 0.1-1.9 mg/l with an optimum concentration range of 0.2-1.7 mg/l. The method
      has been successfully applied to the analysis of chromium in environmental
      samples.

PMID- 14723281
TI  - Performance evaluation of a full-scale coke oven wastewater treatment plant in an
      integrated steel plant.
AB  - Wastewater generated during coke-oven gas cleaning operations in the integrated
      steel plant contains phenol, cyanide, thiocyanate, and also oil and grease.
      Although the activated sludge process is widely practiced for biological
      treatment of coke-oven wastewater, it was observed during the evaluation of
      performance of full scale coke-oven wastewater treatment plant that oil
      contamination and poor sludge settleability had resulted in poor maintenance of
      the activated sludge process. Keeping these aspects in view, treatability studies
      were conducted and an alternative treatment process is proposed. With these
      corrective measures the coke-oven wastewater treatment plant will give desired
      performance. In this paper we present results of the performance evaluation, data
      on treatability studies and alternative treatment process scheme.

PMID- 14723282
TI  - Reorganization of water distribution system of Greater Jammu using computer
      software OPT DIS.
AB  - Water supply in old Jammu city is not evenly distributed due to undulating
      terrain and increase in population density. A study was undertaken to suggest
      measures for improvement to the distribution system. The paper presents results
      of analysis carried out using computer package OPT DIS developed at NEERI for
      optimal design of distribution sytem including system augmentation and
      reorganization measures needed for the design year 2021. The analysis of zone 1
      of the distribution network indicates that seven pipes need alteation to cater to
      the demand for the year 2006 and fifteen pipes need replacement for the year
      2021. New pipelines (13 nos.) are to be provided in parallel to the existing
      pipes in Upper Reach and 28 pipes in Lower Reach to ensure the service standards
      of 225 lpcd with minimum residual head of 17 m. Efficient algorithm for
      augmentations of water supply systems comprising combination of dead-end and loop
      network are having much wider application in developing countries. The software
      OPT DIS developed at NEERI was found to be extremely powerful and user friendly
      for addressing such systems with varying demand pattern, peaking factor, pipe
      condition, water supply modes and design horizones.

PMID- 14723283
TI  - Adsorption studies of chromium (VI) on activated carbon derived from Sorghum
      vulgare (dried stem of Jowar).
AB  - The present work deals with the adsorption studies of chromium (VI) on activated
      carbon derived from Sorghum vulgare (dried stem of Jowar). The activated carbons
      were prepared by physical and chemical activation using H2SO4, H3PO4 activating
      agents of different imprignation Ratio (I.R.). The effect of adsorption of Cr
      (VI) on pH, particle size concentration, contact time and dosage have been
      studied. Removal of chromium (VI) attained in equilibrium maxium of 50 minutes
      and slightly decreases with increasing I.R. Adsorption obeys first order rate
      equation and Webber and Morris equation for pore diffusion. Adsorption increases
      with decrease in pH, is maximum at pH 2. Increase in imprignation ratio also
      increases surface area of Sorghum vulgare carbons.

PMID- 14723284
TI  - Assessment of slow sand filtration system for rural water supply schemes--a case
      study.
AB  - In India, water supply programmes form a part of National Development Plans and
      are implemented in a phased manner under the Five-Year Plans. A number of
      departments and ministries of the Central and State Governments have been vested
      with the responsibility for water supply and sanitation. Due to inherent
      advantages of slow sand filters over conventional rapid sand filters, the
      Panchayat Raj Engineering Department (PRED), Government of Andhra Pradesh has
      designed and constructed a number of slow sand filter plants for rural water
      supply schemes in the state. At the instance of Netherland Assisted Project (NAP)
      Office, Hyderabad, NEERI undertook a critical evaluation of the functioning of
      three slow sand filter plants in Andhra Pradesh and suggested improvements in
      construction, operation and maintenance (O&M) including a review of design
      criteria followed by PRED. The paper presents the outcome of these studies along
      with suggestions needed to bring about improvements in source protection, design,
      construction, O&M of slow sand filter and training programme to improve the
      quality of supervision.

PMID- 14723285
TI  - An improved method for defluoridation.
AB  - Fluoride is a naturally occurring toxic mineral present in drinking water and the
      root cause of many diseases and disorders. Present international drinking water
      standard set by World Health Organisation (WHO) for fluoride is 1.5 ppm. In order
      to find the wide spread concentration of fluoride in drinking water of fluoride
      contaminated aquifer, 30 bore well water samples have been collected from
      different villages of Natrampalli Union which comes under Tiruvannamalai Circle,
      Tamil Nadu, India. In the present work, an attempt to remove fluoride by the use
      of coagulant, Poly Aluminium Chloride (PAC) was made and is compared with the
      most common existing technique "Nalgonda Technique" where there was a reversible
      reaction. The coagulant used in Nalgonda technique is Alum [(Al2SO4)3]. Results
      of the present work show that Poly Aluminium Chloride (PAC) can be an effective
      coagulant for the removal of fluoride from water with a higher removal efficiency
      of about 75 - 85% in less detention time and also observed that the fluoride
      removal was dependent on initial fluoride concentration and dose of coagulants.

PMID- 14723286
TI  - Treatment of chrome plating wastewater (Cr+6) using activated alumina.
AB  - Suitability of activated alumina for removal of hexavalent chromium from
      electroplating wastewater has been investigated. Activated alumina exhibited good
      sorption capacity for hexavalent chromium and pH has no pronounced effect on the
      sorption capacity. Both batch and column adsorption studies have been carried out
      and an adsorption column design indicated reasonable depth of column for
      practical application.

PMID- 14723287
TI  - Physico-chemical and biological investigations of River Umshyrpi at Shillong,
      Meghalaya.
AB  - River Umshyrpi is the major river in Shillong that passes across the city.
      Domestic waste, solid waste, agricultural run off from surrounding areas are
      entering into the river bodies through different drains. Water samples from
      various sites were collected and analysed for physico-chemical and biological
      parameters to assess the quality of the river system. The study reveals that
      physico-chemical parameters are within the permissible limit whereas the
      biological parameters are found to exceed the permissible limit which indicate
      unpotability of water for drinking purposes.

PMID- 14723288
TI  - Integrated management of childhood illness strategy: opportunities and
      challenges.

PMID- 14723289
TI  - Acute respiratory infections in children: a community based longitudinal study in
      south India.
AB  - A community based longitudinal study was conducted in Malpe, a coastal village of
      Udupi district, Karnataka state, to investigate acute respiratory infections
      (ARI) in children. A cohort of 91 children under 3 years of age were followed up
      for 1 year, leading to 2047 fortnightly observation. On an average every child
      had 11.3 months of follow up. The overall incidence of ARI was 6.42 episodes per
      child per year. On an average each episode lasted for 5.06 days. Mean duration of
      ARI during one year was 32.5 days per child. Most of the ARI episodes in children
      (91.3%) were of simple Cough & Cold (no pneumonia). However, 8.2% developed
      pneumonia and only 0.51% had severe pneumonia. Incidence of ARI was almost same
      in male and female children. There was no significant difference in incidence
      among various age groups. But the incidence of pneumonia was significantly higher
      among infants (p<0.00002). Children of poor housing with smoke producing
      conditions suffered more frequently (p,002).

PMID- 14723290
TI  - Assessment of hospital services by consumers: a study from a psychiatric setting.
AB  - The present study revealed perception of forty-five patients and fifty nine
      family members selected from the outpatinet deptt. of a Psychiatric hospital. A
      semi-structured questionnaire was used. The issues like efficiency, punctuality,
      behaviour of doctors and other staff, waiting time, supply of draugs and diet and
      cleanliness of the hospital etc were enquired. More than ninety % of the patients
      and their escorts appreciated the services provided. Most of them (75-80%) was
      satisfied with supply of drugs, quality of diet, clinical care and cleanliness of
      the hospital. Measures for improvement were also suggested.

PMID- 14723291
TI  - Mapping co-variates of mortality up to age of five years for Indian states.
AB  - The study was conducted to obtain an index and a map with natural clusters by
      simultaneously considering sereral covariates of mortality and its indicators
      upto the age of five years for Indian states, Survey reports on various co
      variates of infant mortality and their indicators for the year 1998-99 from
      National Family Health Survey Reports (NFHS II) were studied. Data on ninetten
      covariates of infant and child mortality for twenty major Indian states were used
      for the analysis. The covariates were based on socio-economic, demographic and
      mother's health care variables, morbidity and mortality indicators. An index for
      each state was obtained using statistical technique of factor analysis. Thie
      index measure health care needs of a state relative to the difference between the
      best and the worst states. Mapping of twenty states was done using cluster
      analysis. Eleven states had an inded of above 50, which shows greater care should
      be emphasized on health care variables to reduce mortality. Mapping using cluster
      analysis revealed a picture of natural clusters. The map with the index could
      help the health managers, social scientists and policy makers to identify areas
      that require more interventions. It could also help to comapre the various health
      intervention schemes that have been followed in the states, to devise more
      effective strategies for control of mortality and improvement of survival of
      young children.

PMID- 14723292
TI  - Lymphatic filariasis: constraints ahead.

PMID- 14723293
TI  - Profile of sterilized women in urban slums and evaluation of motivational
      strategies.
AB  - A study undertaken in hard core pockets having C.P.R. >50% of urban slums to
      sensitize target couples for encouraging spacing methods and sterilizations
      showed 55.4% coverage of 1820 unprotected eligible couples. This coverage is
      attributed to involvement of Aganwadi workers, Mahila Mandals and home visits.
      The motivational strategies such as sensitization of Mahila Mondals, provision of
      MCH services and inter personal communications were found to be effective. The
      reasons for non-acceptance, such as desire to have male and female child in
      17.8%, post insertion bleeding due to Cu-T in 13.9% and refusal by male partners
      in 13.36% were noted in eligible couples. These reasons could be removed by
      continued inter personal communications. Illiteracy rate of 76.30% in living
      children of sterilized women indicates need of implementing literacy programme.

PMID- 14723294
TI  - Hypertension among cotton textile workers.
AB  - The present cross sectional study on prevalence of hypertension was carried out
      among 514 cotton textile workers of Shri Bapurao Deshmukh Sut Gimi, Wardha. Using
      standard guidelines for measuring blood pressure and standard criteria for
      diagnosis of hypertension, 20.2% of the subjects were found to have raised
      systolic and/or diastolic blood pressure. The prevalence of hypertension was
      significantly higher among persons aged 35 years or more, in the present
      occupation for 10 years or more and those working in more noisy department.

PMID- 14723295
TI  - Epidemiology of HIV infection among tuberculosis patients in Calcutta.

PMID- 14723296
TI  - Religion and sprituality.

PMID- 14723297
TI  - Religion and spirituality in child and adolescent psychiatry: a new frontier.
AB  - This article introduces the interface between child and adolescent psychiatry and
      religion and spirituality. Developmental psychopathology has become increasingly
      diverse in its study of risk and protective factors for child and adolescent
      psychopathology. The effect of religion and spirituality on clinical conditions
      is among those factors. This review addresses (1) historical aspects of the
      relationship between psychiatry and religion/spirituality, (2) definitional
      issues, and (3) unique factors in child and adolescent work. Considering these
      factors and some general principles of intervention, it prepares the reader for
      other articles in this issue. The article concludes with some observations on the
      "secular family".

PMID- 14723298
TI  - Stages of faith and identity: birth to teens.
AB  - In closing, some of the strengths, limitations, and criticisms of faith
      development theory need to be acknowledged. Fortunately, there was gender balance
      in the formative sample of 359 interviews from which the theory of faith
      development derived (50% each of male and female respondents). In the original
      sample, Protestants made up 45% of the interviewees, Catholics represented 36.5%,
      11.2% were Jews, and 3.6% were Orthodox Christians. A remaining 3.6% were
      "other." Given the growth in the numbers of adherents to other major traditions
      in the United States, interview research needs to be conducted to widen the
      sample to include Muslim, Buddhist, and secular respondents. Interviewees have
      not been studied longitudinally. Furthermore, most of the foundational research
      was conducted in the 1 980s and early 1990s. A new major round of faith
      development interviews could shed light on the impacts on peoples' faith of
      "globalization" and the features of experience that have come to be called the
      "postmodern condition." These phenomena reflect patterns of radical
      secularization and the erosion of religious and moral authority on the one hand
      and, paradoxically, the worldwide growth of fundamentalist and conservative faith
      practices on the other. Add to these phenomena the interest of many "nonchurched"
      persons in "spirituality" and we begin to grasp the richness and diversity that
      faith development research encounters today. Professor Heinz Streib of the
      University of Bielefeld is conducting the most significant research in the faith
      development tradition. The research he and his colleagues are conducting in
      Europe and in the United States promises to yield some tangible data and insights
      into these issues. To date, faith development theory has not been incorporated
      into child, adolescent, and family psychiatric interviewing and case formulation
      to any appreciable or measurable degree. These perspectives and inroads into the
      interior lives and thought processes of young people, however, may be helpful in
      the understanding of normal and pathologic development and of healthy and
      psychiatrically ill children and adolescents. Further collaborative work in this
      area is needed among psychiatrists, clinical psychologists, psychologists of
      religion, religious educators, and theologians.

PMID- 14723299
TI  - Religious and spiritual assessment of the child and adolescent.
AB  - Assessment in child and adolescent psychiatry is a complex process that involves
      developmental, environmental, and experiential perspectives. Recently, there has
      been interest in including spiritual and religious assessment in the psychiatric
      assessment of children, but no well-recognized guidelines for such an assessment
      have been established. This article proposes an approach to spiritual assessment
      of children and adolescents that begins with developing an understanding of the
      family's spiritual and religious life, followed by a developmentally informed
      method of observing and talking with children and adolescents about their
      spiritual and religious beliefs. The article concludes with a discussion of
      ethical issues involved when the psychiatrist addresses issues of spirituality
      and religion with child and adolescent patients and their families.

PMID- 14723300
TI  - Religious and spiritual aspects of family assessment.
AB  - Childhood emotional and behavioral problems have increased over the past several
      decades, and the consequences of these behaviors have an impact on the entire
      family. The role of the family in these problems is clearly an important
      consideration for the child psychiatrist. A specific understanding of how the
      family's spiritual worldview or religious convictions impact clinical problems
      has been underappreciated. The religious orientation or spirituality of parents
      influences various aspects of family life, from ideals about marriage and family
      to specifics regarding child rearing. This article reviews the goals of
      assessment of family religious or spiritual worldview, which include empathically
      engaging the family of a child in treatment, developing a formulation of how
      these spiritual factors impact general family functioning, and determining
      whether the family's religion and spirituality are a resource for treatment or a
      contributor to disorder. The spiritual and religious assessment of the family
      facilitates the development of a treatment plan.

PMID- 14723301
TI  - Formulation and treatment: integrating religion and spirituality in clinical
      practice.
AB  - Developing scientifically sound and clinically meaningful case formulations is so
      challenging that it may verge on becoming a "lost art." Pressures (scientific,
      economic, and cultural) remain that prevent child and adolescent psychiatrists
      from getting a complete understanding of the patient and family. Including a
      strong consideration of data related to religion, spirituality, and worldview may
      seem only to complicate an already arduous task. The clinician who includes these
      factors in treatment is faced with decisions of when to discuss these issues, how
      to discuss them and in what depth, and finally, when to refer to a
      religious/spiritual professional. Nonetheless, the importance of these factors in
      the lives of many children and families leaves no option but to address them as
      directly as possible. It is well worth the effort and, in many cases, will open
      new areas for clinical improvement in patients.

PMID- 14723302
TI  - Religious professionals and institutions: untapped resources for clinical care.
AB  - In the vast majority of situations, religious professionals and institutions are
      competent, caring, and respectful of child and adolescent psychiatrists and
      mental health workers and welcome the opportunity to collaborate to meet the
      religious/spiritual, medical, physical, and emotional needs of children,
      adolescents, and families. Clinicians are well advised to familiarize themselves
      with the religious professionals, institutions, and resources in the geographic
      areas in which they practice.

PMID- 14723303
TI  - Child and adolescent psychopathology: spiritual and religious perspectives.
AB  - This article addresses the relationship between children's religious beliefs and
      spiritual practices and the presence of psychopathology. Study of this subject
      represents a formidable task due to the complexity and diversity of the
      constructs involved, heterogeneity in religious beliefs and practices, and the
      difficulty in discriminating between the independent effects of religion and
      culture. Nevertheless, broad links between child psychopathology and
      spiritual/religious beliefs and practices are proposed. On the whole, the
      available empiric data suggest that religion is primarily health promoting in
      direct, positive benefits for children and in indirect, positive effects through
      parent and family functioning, although there are isolated exceptions. When
      spirituality and religious beliefs/practices are associated with negative mental
      health outcomes in children or their families, evidence points to "poorness-of
      fit," based on an interaction between the child's psychopathology and aspects and
      religious beliefs/practice. Clinical implications of the findings and proposels
      are outlined.

PMID- 14723304
TI  - Spirituality in children confronting death.
AB  - This article uses a developmental framework to consider common spiritual issues
      raised by children and adolescents who are confronting death. The literature
      exploring the role of children's spirituality in addressing death is used to
      illustrate specific areas of concern and topics deserving further research.
      Clinical examples are offered to illustrate the types of situations encountered
      by mental health professionals dealing with seriously ill children and their
      families. Recommendations are offered for concrete approaches for mental health
      professionals dealing with families confronting the death of a child.

PMID- 14723305
TI  - The Jewish child, adolescent, and family.
AB  - This brief review addresses the history, beliefs, and practices of Jewish
      families that have implications for clinical management of the problems and
      disorders of children and adolescents. It focuses primarily on the problems of
      the Orthodox family due, in part, to the limitations of space. There remains,
      however, little doubt that the clinician must be aware of the impact that Jewish
      heritage may have on the clinical issues at hand. This impact is significant
      whether the worldview of the family is characterized by strict Orthodoxy or is
      primarily that of an ethnic identification with less concern for belief and
      practice.

PMID- 14723306
TI  - The Catholic child, adolescent, and family.
AB  - This article identifies core features of Catholic spiritual and religious
      tradition and worldview. It reviews clinical implications of this worldview in
      working with the psychiatric problems of Catholic children and adolescents. Core
      Catholic beliefs and practices are discussed, with case examples illustrating
      principles of assessment and treatment. Collaboration between child and
      adolescent psychiatrists and Catholic clergy and counselors is encouraged, and
      recommendations for successful collaborative efforts are offered.

PMID- 14723307
TI  - The Protestant child, adolescent, and family.
AB  - This article addresses Protestant Christianity as an often-overlooked but
      significant factor in clinical work with children and adolescents. Noting the
      wide range of beliefs and practices among Protestants, the article identifies key
      tenets of Protestant faith that shape the worldviews of children, adolescents,
      and their families. Clinical implications of these beliefs are explored, with
      particular attention to three potentially psychopathologic features: the
      religious legitimation of child maltreatment; paranormal, direct experiences of
      the divine through unusual perceptions such as trance states or visions deemed
      normal within their religious context but that may also evidence serious
      pathology; and sexuality issues of particular significance for adolescents.
      Research suggests that Protestant beliefs also constitute resources for clinical
      work because they appear to be protective factors in relation to depression,
      avoidance of high-risk behaviors, and other measures of resiliency among
      adolescents. Clinicians who do not take the Protestant Christian family's
      religious/spiritual worldview into consideration in case formulation risk
      misunderstanding or alienating them from treatment. The article concludes with
      suggestions for collaboration.

PMID- 14723308
TI  - The muslim child, adolescent, and family.
AB  - This article reviews the basic tenets of Islam, the second-most populous religion
      in the world. The practice of Islam can be affected by ethnic and cultural
      factors; therefore, the influence of various cultures (such as Arab, Pakistani,
      and African American) as seen in practice with Muslim children and their families
      is discussed.

PMID- 14723309
TI  - Hindu and Buddhist children, adolescents, and families.
AB  - The language of psychotherapy that focuses on the individual may be problematic
      for Hindu and Buddhist families. The focus on child and adolescent development as
      a separation-individuation process that moves the child into an independent life
      with individual goals may run contrary to family cultural values and to the Hindu
      and Buddhist views of interconnectedness. For the Hindu family, however, when
      therapy can be seen as being compatible with an evolution toward the higher self
      and is consistent with the shared sense of family belonging, the goals can be
      complementary. With the fundamental views in Buddhism that suffering derives from
      emotional and conceptual misunderstandings and from the resultant actions, and
      that change is necessary to relieve that suffering, therapy and practice may
      share goals. The spiritual teachings can work alongside the therapeutic work, and
      the improved functioning is also spiritual growth.

PMID- 14723310
TI  - Spirituality in children and adolescents: research findings and implications for
      clinicians and researchers.
AB  - Spirituality is a powerful force in the lives of children. Although spirituality
      has only recently begun to be a focus for psychiatric research, initial
      qualitative data suggest that children experience themselves as spiritual beings
      and that understanding and connecting with them around their spiritual lives can
      be an important adjunct to treatment. Clinicians should feel free to ask about a
      child's spiritual life and to work with the family using their spiritual
      resources if they are perceived to be beneficial in helping the child and family
      cope with their current situation. Because the work with children's spirituality
      is in its preliminary stages, qualitative methodology is still the recommended
      research method for investigating questions in this research area.

PMID- 14723311
TI  - Neurophysiology of pain: insight to orofacial pain.
AB  - This is a very exciting time in the field of pain research. Major advances are
      made at every level of analysis from development to neural plasticity in the
      adult and from the transduction of a noxious stimulus in a primary afferent
      neuron to the impact of this stimulus on cortical circuitry. The molecular
      identity of nociceptors, their stimulus transduction processes and the ion
      channels involved in the generation, modulation and propagation of action
      potentials along the axons in which these nociceptors are present are being
      vigorously perused. Similarly tremendous progress has occurred in the
      identification of the receptors, transmitters, second messenger systems,
      transcription factors, and signaling molecules underlying the neural plasticity
      observed in the spinal cord and brainstem after tissue or nerve injury. With
      recent insight into the pharmacology of different neural circuits, the importance
      of descending modulatory systems in the response of the nervous system to
      persistent pain after injury is being reevaluated. Finally, imaging studies
      revealed that information about tissue damage is distributed at multiple
      forebrain sites involved in attentional, motivational, and cognitive aspects of
      the pain experience.

PMID- 14723312
TI  - Evaluation of intraperitoneal vincristine in malignant peritoneal effusion.
AB  - The efficacy and safety of intraperitoneal administration of vincristine sulphate
      was determined in mice bearing Ehrlich ascitic carcinoma. The tumor bearing
      animals were administered with 0.5 mg/kg body weight (b.wt) of freshly prepared
      vincristine sulphate intraperitoneally on day 6 after tumor transplantation
      followed by drug administration once daily 5 days a week consecutively. The
      observations regarding the survival, alteration in the volume of peritoneal
      fluid, increase in life span and pathological changes in the liver, kidney,
      gastrointestinal tract and bone tissues were made. The vincristine sulphate
      treatment reduced the malignant cell population significantly and there were no
      significant changes in the histological picture of liver, kidney, bone, except
      the intestine, where atropy of villi demonstrating nests and cords of uniform
      small round cells were observed. Our experimental data suggests that
      intraperitoneal administration of vincristine is beneficial in malignant
      peritoneal effusion.

PMID- 14723313
TI  - Cardiorespiratory responses to submaximal incremental exercise are not affected
      by one night's sleep deprivation during the follicular and luteal phases of the
      menstrual cycle.
AB  - The purpose of the study was to investigate the effects of one night's sleep
      deprivation on the cardiorespiratory responses to exercise during the follicular
      and luteal phases of the menstrual cycle. We have studied nine, healthy females
      aged 24-35 years with regular menstrual cycles. Each subject performed
      spirometric tests at rest and then an incremental exercise testing during 11-13
      days of follicular phase and 22-24 days of luteal phase following one normal
      night's sleep or one night's sleep loss. Compared with resting values exercise
      produced significant increases in cardiorespiratory variables including oxygen
      uptake (VO2), carbon dioxide production (VCO2), tidal volume (VT), respiratory
      rate (RR), minute ventilation (VE), systolic blood pressure, heart rate (HR) and
      respiratory quotient (R). However, it did not alter significantly diastolic blood
      pressure, end-tidal PO2 (PETO2), end-tidal PCO2 (PETCO2) and arterial oxygen
      saturation (SaO2). Spirometric variables which include forced vital capacity
      (FVC), forced expiratory volume in one s (FEV1), FEV1/FVC%, forced expiratory
      volume in three s (FEV3), forced expired flow from 25-75% of FVC (FEF 25-75%),
      forced expired flow at 25% of FVC (FEF 25%), forced expired flow at 50% of FVC
      (FEF 50%), forced expired flow at 75% of FVC (FEF 75%), forced expired flow from
      75-85% of FVC (FEF 75-85%), peak expiratory flow (PEF), expiratory reserve volume
      (ERV), inspiratory capacity (IC) and maximal voluntary ventilation (MVV) and
      cardiorespiratory variables were not different between the cycle phases after one
      normal night's sleep or one night's sleep deprivation. Neither menstrual cycle
      phase nor sleep deprivation affected spirometric and cardiorespiratory
      parameters. We suggest that one night's sleep deprivation does not produce
      alterations in spirometric parameters and cardiorespiratory responses to
      submaximal incremental exercise during the follicular and luteal phases.

PMID- 14723314
TI  - Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced
      immune responses by bicuculline.
AB  - The present study investigates the effect of progesterone, a pregnane precursor
      of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for
      mitochondrial diazepam binding inhibitor receptor (MDR) involved in
      neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and
      cell-mediated immune responses. RS produced a significant reduction in anti-sheep
      red blood cells (SRBC) antibody titre, a measure of humoral immune response, and
      % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of
      cell-mediated immune responses. These effects of RS on immune responses were
      effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc)
      or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS.
      The effect of both progesterone and 4'-CD on RS-induced immune modulation was
      significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10
      mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone
      (5, 10 mg/kg, sc) when administered to non-stressed animals produced a
      significant suppression of both humoral and cell-mediated immune responses which
      was not reversed by bicuculline. However, 4'-CD failed to modulate immune
      response in naive non-stressed animals. These results suggest that progesterone
      and 4'-CD affect stress-induced immune responses by modulating GABA-ergic
      mechanism. However, GABA-A receptor system does not appear to be involved in
      progesterone-induced immunosuppression in nonstressed animals.

PMID- 14723315
TI  - Acute effect of Mukh bhastrika (a yogic bellows type breathing) on reaction time.
AB  - Reaction time (RT) is an index of the processing ability of central nervous
      system and a simple means of determining sensory-motor performance. It has been
      reported that yoga training improves human performance including central neural
      processing. Earlier studies from our laboratories have shown that yoga training
      produces a significant decrease in visual reaction time (VRT) and auditory
      reaction time (ART). The present work was planned to determine if mukh bhastrika
      (a yogic technique in which breath is actively blasted out in 'whooshes'
      following a deep inspiration) has any effect on central neural processing by
      studying its effect on RT. 22 healthy schoolboys who were practising yoga for the
      past three months were recruited for the present study. VRT and ART were recorded
      before and after nine rounds of mukh bhastrika. Mukh bhastrika produced a
      significant (P < 0.01) decrease in VRT as well as ART. A decrease in RT indicates
      an improved sensory-motor performance and enhanced processing ability of central
      nervous system. This may be due to greater arousal, faster rate of information
      processing, improved concentration and/ or an ability to ignore extraneous
      stimuli. This is of applied value in situations requiring faster reactivity such
      as sports, machine operation, race driving and specialised surgery. It may also
      be of value to train mentally retarded children and older sports persons who have
      prolonged RT.

PMID- 14723316
TI  - Effects of iron therapy on cognition in anemic school going boys.
AB  - The present study was conducted on 18 anemic and 34 control subjects (mean age
      9.26 +/- 0.26 years) to observe the effect of anemia on cognition and to see
      effect of 3 months of iron therapy on it. Anemia was defined on the basis of
      hematological values and peripheral smear examinations. Cognitive data consisted
      of the recording of the P300 wave of Auditory Event Related Potentials (AERP),
      Ravens Progressive Matrices Test (RPMT), and Digit Span Attention Test (DSAT)
      under standard test conditions. RPMT scores were then converted to the
      intelligence quotient (IQ) scores for comparison. Both anemic and control boys
      were dewormed after recording pretreatment values and then anemic boys were given
      iron therapy for 3 months, after which the recordings were taken again.
      Pretreatment, anemic boys showed significantly lower hematological values,
      delayed P300 latency, and lower RPMT scores as compared to controls. Post therapy
      the hematological profile of anemic boys though significantly improved as
      compared to the pretreatment values, was still significantly lower than that of
      control boys. The P300 latency values of anemic boys showed improvement but were
      still significantly delayed than the control group. RPMT values and derived IQ
      scores of anemic boys were similar to control boys after therapy suggesting that
      though the 3 months iron therapy regime resulted in improvement in psychometric
      cognitive tests in anemic boys, the basic P300 defects persisted. This suggests
      that the P300 component of AERP in anemic children is relatively refractory to 3
      months of iron therapy.

PMID- 14723317
TI  - Enkephalinergic involvement in substantia nigra in the modulation of
      hypothalamically-induced predatory attack behavior.
AB  - The present study was carried out in five cats which did not attack the rats
      spontaneously. Predatory attack on an anaesthetized rat was elicited by
      electrical stimulation of lateral hypothalamus at a mean current strength of 650
      microA. The attack was accompanied by minimal affective display and culminated in
      neck biting. Microinfusions of DAME (delta-alanine methionine enkephaline) in 500
      ng dose in substantia nigra facilitated the predatory attack and there was a
      significant reduction in the threshold current strength for affective display as
      well as somatomotor components. Microinfusions of naloxone, an opioid antagonist
      in 1.0 microg dose when DAME effect was at its peak reversed the facilitatory
      effects and the threshold returned to the control levels within 10 minutes of
      naloxone infusion at the same locus. Microinfusions of naloxone alone in similar
      dosage completely blocked the predatory attack response as indicated by an
      increase in the threshold current strength for somatomotor as well as affective
      display components. The somatomotor were completely inhibited and could not be
      elicited even when the current strength was increased to 1000 microA. Control
      injections of saline in similar volumes (0.5 microl) failed to produce any
      response Microinfusions of naloxone in lower dose (250 ng) failed to produce any
      blocking effect. These findings indicate that hypothalamically elicited predatory
      attack is facilitated by enkephalinergic mechanisms operating at the midbrain
      level.

PMID- 14723318
TI  - Sildenafil improves acquisition and retention of memory in mice.
AB  - Sildenafil (Viagra) has been introduced recently in market to correct male
      impotency and has gained immense popularity for its dramatic effects all over the
      world. The present study was designed to investigate the effect of sildenafil on
      learning and memory in mice using elevated plus maze. A total of XV groups of
      animals were employed in the present study. Central cholinergic pathways play a
      crucial role in learning and memory processes. Physostigmine, an
      anticholinesterase agent (0.5 mg, 1.0 mg kg(-1), i.p) was employed for its memory
      enhancing property and alprazolam a benzodiazepine receptor agonist served as a
      memory-impairing agent. In the present study, alprazolam produced anterograde
      amnesia (at 0.5 mg kg(-1), i.p) and retrograde amnesia (at 0.25 mg, 0.5 mg, 0.75
      mg kg(-1), i.p.) in separate groups of animals. Caffeine at 5 mg, 10 mg and 20 mg
      kg(-1), i.p. (an established psychostimulant) did not show any significant change
      in learning and memory of mice. Sildenafil (at 8 mg kg(-1), i.p.) administered 30
      minutes prior to training on first day produced a marginal decrease in transfer
      latency time on first day; whereas, sildenafil (at 2 mg, 4 mg, 8 mg kg(-1), i.p.)
      administered immediately after training on first day produced a dose-dependent
      improvement of memory in mice. However, further studies need to be carried out to
      elucidate the underlying mechanism of sildenafil as a memory enhancer.

PMID- 14723319
TI  - Effect of acute and chronic conditions of over-crowding on free choice ethanol
      intake in rats.
AB  - Male albino rats of Wistar strain were exposed to overcrowding stress in two
      different groups for a period of seven days. One group of rats was kept under
      stress for six hours per day (acute stressed group) and the other group rats was
      kept under stress continuously (chronic stressed group). The effect of these
      acute and chronic stresses on voluntary alcohol (2% w/v) intake was monitored
      during the 7 days of stress exposure, and ethanol preference and total ethanol
      intake in terms of g/kg body weight were also studied. A significant increase in
      ethanol preference and ethanol intake was observed in one-day and 7 days chronic
      stressed group. No significant increase in ethanol intake was observed in acute
      stress. Thus a short lasting stressor may not increase ethanol-drinking behavior,
      whereas when animals were exposed to more intense stressor continuously for 7
      days, an increase in voluntary drinking behavior may be seen.

PMID- 14723320
TI  - Hepatobiliary clearance of labelled mebrofenin in normal and D-galactosamine HCl
      induced hepatitis rats and the protective effect of turmeric extract.
AB  - This study was carried out to see the hepatobiliary clearance of 99m Tc
      Mebrofenin radiopharmaceutical in D-galactosamine induced hepatic rats.
      Furthermore, protective effect of turmeric extract has been studied in these
      hepatitis rats. Hepatitis was induced with intraperitoneal injection of D
      galactosamine (400 mg/kg b. wt) in these rats. 1% turmeric extract was given
      along with their normal diet for 15 days. Turmeric extract treatment
      significantly increased the hepatic uptake of radioactivity and accelerated the
      excretion of 99m Tc-Mebrofenin as compared to control rats. (P < 0.001). In D
      galactosamine administered rats, a significant delay was observed in 99m Tc
      Mebrofenin excretion as compared to controls. However, D-galactosamine
      administered rats, pretreated with turmeric extract or concurrently treated with
      turmeric extract showed a near normal pattern of 99m Tc-Mebrofenin excretion.
      Hence, it can be suggested that turmeric extract may improve the liver function
      by detoxification.

PMID- 14723321
TI  - Lung function tests in electroplaters of East Delhi.
AB  - The presence of high concentration of metals (Cr, Cd, Co, Ni, Pb, etc.) in the
      work place environments of various types of industries including electroplating
      units are well known to influence respiratory system. Pulmonary function tests
      including forced expiratory capacity (FVC), volumes, mechanics and slow vital
      capacity (SVC) were studied in 80 males, divided into group I and Group II of 40
      each were drawn from electroplating and non-electroplating units, respectively
      from East Delhi factories. The lung function tests were measured using
      computerized Spiro-232 of P.K. Morgan, Values of majority of lung function
      parameters such as FEV1/FVC%, FEF50 FEF75, PIFR, FIF50, MVV and SVC were
      decreased in electroplaters, perhaps due to the exposure to metals and their
      lower anthropmetric results as compared with non electoplaters. Where as results
      of TLC, FRC, RV & RV/ TLC% were higher in electroplaters and this may be
      attributed to higher values of RV in them as compared with non electroplaters.

PMID- 14723322
TI  - Status of blood antioxidant enzymes in alcoholic cirrhosis.
AB  - Chronic alcohol consumption is associated with increased incidence of variety of
      illnesses including cirrhosis. Studies have shown that ethanol consumption may
      result in increased oxidative stress with increased formation of lipid peroxides
      and free radicals. However, very few reports are available on their involvement
      in the toxicity of alcoholic cirrhosis. The present study was undertaken in 44
      male subjects to evaluate the role of oxidative stress in liver injury with
      special reference to alcoholic or non alcoholic cirrhosis. It was observed that
      the parameters of liver function like total bilirubin, Alanine Transaminase
      (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), gamma Glutamyl
      transfarase (gammaGT) were increased in cirrhotic (alcoholic or non alcoholic)
      patients as compared to normal controls. However antioxidant enzymes like
      Superoxide dismutase (SOD) and Glutathine peroxidase (GPx) lipid peroxidation
      marker, Malondialdehyde (MDA) showed significant changes only in alcoholic
      cirrhosis and not in non alcoholic cirrhosis when compared with normal controls.
      The possibility of assessment of antioxidant enzymes to differentiate between
      alcoholic or non alcoholic or non alcoholic cirrhosis is postulated.

PMID- 14723323
TI  - Effect of nimodipine, a dihydropyridine calcium channel antagonist on the
      pharmacokinetics of carbamazepine in rhesus monkeys.
AB  - Calcium channel antagonists have been shown to have an anticonvulsant activity in
      a variety of seizure models and also to potentiate the anticonvulsant activity of
      other standard antiepileptic drugs like carbamazepine, phenytoin and valporoate.
      A pharmacokinetic interaction may be involved in such potentiation. This cross
      over single dose study was carried out to find out if there was a pharmacokinetic
      interaction between carbamazepine, a commonly used antiepileptic drug and
      nimodipine, a dihydropyridine calcium channel antagonist in rhesus moneys.
      Carbamazepine 46 mg/kg and nimodipine 9.6 mg/kg was administered through a
      nasogastric tube and blood samples were collected at 0.5, 1, 2, 3, 6, 9, 12, 24,
      48, 72 and 96 hours after drug administration and were assayed for carbamazepine.
      Nimodipine caused a significant increase in peak plasma concentration (C(max)) of
      carbamazepine and a decrease in plasma absorption half life (t1/2 alpha). There
      was no significant change in other pharmacokinetic parameters between the two
      groups. The results of the study suggest that concurrent administration of
      carbamazepine and nimodipine may cause a significant rise in carbamazepine
      concentration as may contribute to a potentiation of anticonvulsant effect of
      carbamazepine and an increase in the incidence of adverse effects warranting that
      nimodipine should be prescribed cautiously in epileptic patients receiving
      carbamazepine and it might be very appropriate to do therapeutic drug monitoring
      of carbamazepine in such patients.

PMID- 14723324
TI  - A longitudinal study of antenatal changes in lung function tests and importance
      of postpartum exercises in their recovery.
AB  - A study of changes in lung function tests during pregnancy was undertaken in
      fifty pregnant women beginning from third month of gestation. Fifty nonpregnant
      age and height matched women formed the controls. Forced Vital Capacity (FVC),
      Timed Vital Capacity (FEV1), Inspiratory Capacity (IC), Expiratory Reserve Volume
      (ERV) and peak Expiratory Flow Rate (PEFR) were performed in each month of
      pregnancy. However ten subjects were not available for follow-up during
      postpartum period. Remaining forty women were divided into two groups of twenty
      each. Group I performed daily graded active exercises to strengthen the anterior
      abdominal wall muscles. Group II women did not perform any exercises. It was
      observed that the antenatal changes in percent FVC and FEV1 were insignificant,
      but the decline in ERV and PEFR were very highly significant (P < 0.001) and the
      increment in IC was significant (P < 0.05). In the postpartum period the
      percentage variation of values in group I was less than 5% from controls (P >
      0.05) and in group II it was 15-20% from controls (P < 0.05), resulting in a
      significant variation in group II women as compared to the controls. It is
      concluded that there are adaptive changes in lung functions in the antenatal
      period. We stress the importance of regular graded active exercises in the
      postpartum period for the speedy recovery of these changes.

PMID- 14723325
TI  - Study of serum lipid profile changes in Met-enkephalin treated rats.

PMID- 14723326
TI  - Is there a secular trend in the menarcheal age of Indian girls?

PMID- 14723327
TI  - Evaluation of the efficacy of bitter gourd (momordica charantia) as an oral
      hypoglycemic agent--a randomized controlled clinical trial.

PMID- 14723328
TI  - Synthesis of 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4
      methoxyphenyl)benzofuran as a beta-amyloid aggregation inhibitor.
AB  - An efficient synthesis of 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4
      methoxyphenyl)benzofuran (8), a potent beta-amyloid aggregation inhibitor, is
      described. 5-Chloro-2-(4-methoxyphenyl)benzofuran (3) was obtained by the one-pot
      synthesis of 4-chlorophenol with omega-(methylsulfinyl)-p-methoxyacetophenone (1)
      under Pummerer reaction conditions, and it was followed by the desulfurization of
      the resultant 5-chloro-3-methylthio-2-(4-methoxyphenyl)benzofuran (2e). Acylation
      of benzofuran 3 with 4-(3-bromopropoxy)benzoyl chloride (6) gave the ketone 7,
      which was converted into compound 8 by the treatment of diethylamine.

PMID- 14723329
TI  - Synthesis of novel carboacyclic nucleosides with vinyl bromide moiety as open
      chain analogues of neplanocin A.
AB  - A novel carboacyclic nucleoside analogue, 9-[2-bromo-4-hydroxy-3-hydroxymethyl-2
      butenyl] adenine, and its derivatives were designed and synthesized as open-chain
      analogues of neplanocin A. The syntheses were accomplished via the coupling of
      adenine or pyrimidine bases to the key intermediate allylic bromide 7. The
      bromide 7 was prepared from epichlorohydrin in a seven step process in a 54%
      overall yield. The synthesized compounds were evaluated for their antiviral
      activity against the polio virus, HSV and HIV.

PMID- 14723330
TI  - Lipase mediated chiral resolution of 4-arylthio-2-butanol as an intermediate for
      beta-lactam antibiotics.
AB  - This paper deals with chiral enzymatic resolution of 4-arylthio-2-butanols by
      lipase to prepare potential intermediates of beta-lactam antibiotics. Among
      several lipases employed, lipase P type enzyme gave the highest ee value to
      prepare (R)-4-arylthio-2-butyl acetate. The enzymatic resolution of phenyl
      substituted alcohol (6a) using lipase P showed the highest ee value (99.7%) among
      those of 4-arylthio-2-butanol derivatives. Lipase P mediated hydrolysis of
      acylester 7a gave also (R)-alcohol 6a selectively. For determination of
      enantiomeric purity of these enzymatic resolved analytes, liquid chromatographic
      analysis was performed using two coupled Chiralcel OD and (R,R)-WhelkO chiral
      column.

PMID- 14723331
TI  - Characterization of physicochemical properties of ferulic acid.
AB  - Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component
      possessing antioxidant property. The compound is currently under development as a
      new drug candidate for the treatment of the dementia. The objective of this
      preformulation study was to determine the physicochemical properties of ferulic
      acid. The n-octanol to water partition coefficients of ferulic acid were 0.375
      and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for
      ferulic acid indicated that the t 90 value for the drug was estimated to be 459
      days at 25 degrees C. Ferulic acid was also found to be unstable under the
      relative humidity of more than 76%, probably because of the hygroscopic nature of
      the drug. In order to study compatibility of ferulic acid with typical
      excipients, potential change in differential scanning calorimetry spectrum was
      studied in 1:1 binary mixtures of ferulic acid and typical pharmaceutical
      excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and
      talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic
      acid, indicating the addition of these excipients may complicate the
      manufacturing of the formulation for the drug. Particle size distribution of
      ferulic acid powder was in the size range of 10-190 microm with the mean particle
      size of 61 microm. The flowability of ferulic acid was apparently inadequate,
      indicating the granulation may be necessary for the processing of the drug to
      solid dosage forms. Two polymorphic forms were obtained by recrystallization from
      various solvents used in formulation. New polymorphic form of ferulic acid, Form
      II, was obtained by recrystallization from 1,4-dioxane. The equilibrium
      solubility for Form I was approximately twice of that for Form II. The
      dissolution rate of Form II was higher than that of Form I in the early phase (<6
      min). Therefore, these physicochemical information has to be taken in the
      consideration for the formulation of ferulic acid.

PMID- 14723332
TI  - A new pterocarpan, (-)-maackiain sulfate, from the roots of Sophora subprostrata.
AB  - A new pterocarpan, (-)-maackiain 3-sulfate (1) was isolated from the methanol
      extract of roots of Sophora subprostarata together with (-)-maackiain (2),
      trifolirhizin (3), lupeol (4), ononin (5), 7,4'-dihydroxyflavone (6), and (+)
      syringaresinol (7). The structure of 1 was determined by analyses of 2D NMR and
      HRFABMS. Compounds 5-7 were isolated from this plant for the first time.

PMID- 14723333
TI  - Two new phenylpropanoid glycosides from the stem bark of Acanthopanax
      trifoliatus.
AB  - Two new phenylpropanoid glycosides, 1-beta-D-glucopyranosyl-2,6-dimethoxy-4
      propenylphenol (1) and 1-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]
      2,6-dimethoxy-4-propenylphenol (2) were isolated from the stem bark of
      Acanthopanax trifoliatus along with four known compounds (3-6). Their structures
      were established on the basis of spectral and chemical evidences.

PMID- 14723334
TI  - Constituents of the stems and fruits of Opuntia ficus-indica var. saboten.
AB  - From the stems and fruits of Opuntia ficus-indica var. saboten, eight flavonoids,
      kaempferol (1), quercetin (2), kaempferol 3-methyl ether (3), quercetin 3-methyl
      ether (4), narcissin (5), (+)-dihydrokaempferol (aromadendrin, 6), (+)
      dihydroquercetin (taxifolin, 7), eriodictyol (8), and two terpenoids, (6S,9S)-3
      oxo-alpha-ionol-beta-D-glucopyranoside (9) and corchoionoside C (10) were
      isolated and identified by means of chemical and spectroscopic. Among these
      isolates, compounds 3-5 and 8-10 were reported for the first time from the stems
      and fruits of O. ficus-indica var. saboten.

PMID- 14723335
TI  - A prolyl endopeptidase-inhibiting antioxidant from Phyllanthus ussurensis.
AB  - A prolyl endopeptidase inhibitor was isolated from the ethyl acetate soluble
      fraction of Phyllanthus ussurensis. The active compound was identified as an
      ellagitannin, corilagin. It was shown to non-competitively inhibit prolyl
      endopeptidase (PEP) with the IC50 value of 1.17x10(-6) microM. The Ki value was
      6.70x10(-7) M. Corilagin was less inhibitory to other serine proteases such as
      chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific
      inhibitor of PEP. Corilagin also effectively inhibited reactive oxygen species
      such as hydroxide and superoxide anion radical, hydrogen peroxide, and DPPH.
      Especially, corilagin showed potent scavenging activity on the superoxide anion
      radical in the ESR method (IC50 = 3.79x10(-6) M) as well as xanthine oxidase
      system.

PMID- 14723336
TI  - Inhibition of IL-1beta and IL-6 in osteoblast-like cell by isoflavones extracted
      from Sophorae fructus.
AB  - Osteoporosis is recognized as one of the major hormonal deficiency diseases,
      especially in menopausal women and the elderly. When estrogen is reduced in the
      body, local factors such as IL-1beta and IL-6, which are known to be related with
      bone resorption, are increased and promote osteoclastogenesis, which is
      responsible for bone resorption. In the present study, we investigated whether
      glucosidic isoflavones (Isocal, PIII) extracted from Sophorae fructus affect the
      proliferation of osteoblasts and prevent osteoclastogenesis in vitro by
      attenuating upstream cytokines such as IL-1beta and IL-6 in a human osteoblastic
      cell line (MG-63) and in a primary osteoblastic culture from SD rat femurs.
      Interestingly, IL-1beta and IL-6 mRNA were significantly suppressed in osteoblast
      like cells treated with 17beta-estradiol (E2) and PIII when compared to positive
      control (SDB), and this suppression was more effective at 10(-8)% than at the
      highest concentration of 10(-4)%. In addition, these were confirmed in protein
      levels using ELISA assay. In the cell line, the cells showed that E2 was the most
      effective in osteoblastic proliferation over the whole range of concentration
      (10(-4)%-10(-12)%), even though PIII also showed the second greatest
      effectiveness at 10(-8)%. Nitric oxide (NO) was significantly (p<0.05)
      upregulated in PIII and E2 over the concentration range 10(-6)% to 10(-8)% when
      compared to SDB, without showing any dose dependency. In bone marrow primary
      culture, we found by TRAP assay that PIII effectively suppressed
      osteoclastogenesis next to E2 in comparison with SDB and culture media (control).
      In conclusion, these results suggest that local bone-resorbing cytokines can be
      regulated by PIII at lower concentrations and that, therefore, PIII may
      preferentially induce anti-osteoporosis response by attenuating osteoclastic
      differentiation and by upregulating NO.

PMID- 14723337
TI  - Characteristics of chitosanases from Aspergillus fumigatus KB-1.
AB  - Two chitosanases produced by Aspergillus fumigatus KB-1 were purified by ion
      exchange and size exclusion chromatographies. Molecular weights of chitosanases
      were 111.23 kDa (chitosanase I) and 23.38 kDa (chitosanase II). The N-terminal
      amino acid sequence of chitosanase II was determined as follows:
      YNLPNNLKQIYDKHKGKXSXVLAKGFTN. The optimum pH of the chitosanase I and II was 6.5
      and 5.5, respectively. The optimum temperatures were 60 degrees C for chitosanase
      land 70 degrees C for chitosanase II. Hydrolysis products of two chitosanases
      were analyzed by HPLC and GPC. Chitosanase I hydrolyzed substrate to glucosamine.
      Chitosanase II produced chitooligosaccharides.

PMID- 14723338
TI  - Hypocholesterolemic property of Yucca schidigera and Quillaja saponaria extracts
      in human body.
AB  - This study was undertaken to observe the effects of the blend of partially
      purified Yucca schidigera and Quillaja saponaria extracts on cholesterol levels
      in the human's blood and gastrointestinal functions, and to determine if a new
      cholesterol-lowering drug can be developed by the further purification of the
      extracts. Ultrafiltration and sequential diafiltration increased the amounts of
      steroidal saponin in aqueous yucca extract and terpenoid saponin in aqueous
      quillaja extract from 9.3% and 21.4% to 17.2% and 61.8%, respectively. Taking 0.9
      mg of the blend (6:4, v:v) of the resulting filtrates a day for 4 weeks resulted
      in the decreases in total and LDL cholesterol levels in blood plasma of hyper
      cholesterolemic patients with enhancement in gastrointestinal symptoms of
      patients.

PMID- 14723339
TI  - Identification of alkylation-sensitive target chaperone proteins and their
      reactivity with natural products containing Michael acceptor.
AB  - Molecular chaperones have a crucial role in the folding of nascent polypeptides
      in endoplasmic reticulum. Some of them are known to be sensitive to the
      modification by electrophilic metabolites of organic pro-toxicants. In order to
      identify chaperone proteins sensitive to alkyators, ER extract was subjected to
      alkylation by 4-acetamido-4'-maleimidyl-stilbene-2,2'-disulfonate (AMS), and
      subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57
      and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant
      chaperon protein was identified to be protein disulfide isomerase (PDI) in
      comparison with the purified PDI. To see the reactivity of PDI with cysteine
      alkylators, the reduced form (PDIred) of PDI was incubated with various
      alkylators containing Michael acceptor structure for 30 min at 38 degrees C at pH
      6.3, and the remaining activity was determined by the insulin reduction assay.
      Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated PDIred with N
      ethylmaleimide being more potent than iodoacetamide. A partial inactivation of
      PDIoxid was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3.
      Of Michael acceptor compounds tested, 1,4-benzoquinone (IC50, 15 microM) was the
      most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast,
      1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to
      cause the oxidative conversion of PDIred to PDIoxid. Thus, the action of Michael
      acceptor compounds differed greatly depending on their structure. Based on these,
      it is proposed that PDI, one of chaperone proteins in ER, could be susceptible to
      endogenous or xenobiotic Michael acceptor compounds in vivo system.

PMID- 14723340
TI  - Lysophosphatidic acid inhibits melanocyte proliferation via cell cycle arrest.
AB  - Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types.
      However, we found that LPA inhibits melanocyte proliferation. Thus, we further
      investigated the possible signaling pathways involved in melanocyte growth
      inhibition. We first examined the regulation of the three major subfamilies of
      mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The
      activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N
      terminal kinase (JNK) were observed in concert with the inhibition of melanocyte
      proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA.
      However, the specific inhibition of the ERK or JNK pathways by PD98059 or D
      JNKI1, respectively, did not restore the antiproliferative effect. We next
      examined changes in the expression of cell cycle related proteins. LPA decreased
      cyclin D1 and cyclin D2 levels but increased p21(WAF1/CIP1) (p21) and p27KIP1
      (p27) levels, which are known inhibitors of cyclin-dependent kinase. Flow
      cytometric analysis showed the inhibition of DNA synthesis by a reduction in the
      S phase and an increase in the G0/G1 phase of the cell cycle. Our results suggest
      that LPA induces cell cycle arrest by regulating the expressions of cell cycle
      related proteins.

PMID- 14723341
TI  - Anti-inflammation activity of Actinidia polygama.
AB  - The fruit of Actinidia polygama (AP) has long been used as a folk medicine in
      Korea for treating pain, rheumatic arthritis and inflammation. The present
      investigation was carried out to determine the in vivo and in vitro anti
      inflammatory activity of AP using several animal models of inflammation. The 70%
      ethanol extract of the fruit of AP significantly inhibited acetic acid-induced,
      vascular permeability in a dose dependent manner (23%, 38%, and 41% inhibition at
      doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg, respectively). This effect was
      maintained in AP water-soluble fraction (APW). The APW fraction also showed
      significant inhibitory activity against the rat paw edema induced by a single
      treatment of carrageenan. In vitro experiments were performed to demonstrate the
      inhibitory activities of APW (100 microg/ml) on lipopolysaccharide (LPS)-induced
      nitric oxide (NO) and prostaglandin E2 (PGE2) production. The results showed that
      APW dose-dependently suppressed LPS-induced NO production in RAW 264.7
      macrophages without a notable cytotoxic effect and also decreased inducible NO
      synthase (iNOS) protein expression. APW also showed a significant inhibitory
      effect in LPS-induced PGE2 production and cyclooxygenase-2 (COX-2) expression.

PMID- 14723342
TI  - Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1 beta and nitric
      oxide in rat microglia.
AB  - Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread
      clinical use mainly for acute and chronic liver disease. Recently, treatment with
      UDCA in hepatic graft-versus-host disease has been given in immunosuppressive
      therapy for improvement of the biochemical markers of cholestasis. Moreover, it
      has been reported that UDCA possesses immunomodulatory effects by the suppression
      of cytokine production. In the present study, we hypothesized that UDCA may
      inhibit the production of the pro-inflammatory cytokine, IL-1beta, and nitric
      oxide (NO) in microglia. In the study, we found that 100 microg/mL UDCA
      effectively inhibited these two pro-inflammatory factors at 24 h and 48 h,
      compared to the Abeta42-pretreated groups. These results were compared with the
      LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by
      several stimulants, such as Abeta42, in Alzheimers brain and can release those
      inflammatory factors, the ability to inhibit or at least decrease the production
      of IL-1beta and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA
      and the Griess Reagent System, we therefore found that UDCA in Abeta42 pre
      treated cultures played a significant role in suppressing the expression or the
      production of IL-1beta and NO. Similarly, lipopolysaccharide (LPS) did not
      activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits
      a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may
      play an important role in chronic cell damage due to this long effect. These
      results further imply that UDCA could be an important cue in suppressing the
      microglial activation stimulated by massive Aa peptides in the AD progressing
      brain.

PMID- 14723343
TI  - Inhibitory effects of glycine on morphine-induced hyperactivity, reverse
      tolerance and postsynaptic dopamine receptor supersensitivity in mice.
AB  - The effects of glycine on morphine-induced hyperactivity, reverse tolerance and
      postsynaptic dopamine receptor supersensitivity in mice was examined. A single
      administration of morphine (10 mg/kg, s.c.) induced hyperactivity as measured in
      mice. The morphine-induced hyperactivity was inhibited by pretreatment with
      glycine (100, 200 and 400 mg/kg, i.p.). In addition, it was found repeated
      administration of morphine (10 mg/kg, s.c.) to mice daily for 6 days caused an
      increase in motor activity which could be induced by a subsequent morphine dose,
      an effect known as reverse tolerance or sensitization. Glycine (100, 200 and 400
      mg/kg, i.p.) also inhibited morphine-induced reverse tolerance. Mice that had
      received 7 daily repeated administrations of morphine also developed postsynaptic
      dopamine receptor supersensitivity, as shown by enhanced ambulatory activity
      after administration of apomorphine (2 mg/kg, s.c.). Glycine inhibited the
      development of postsynaptic dopamine receptor supersensitivity induced by
      repeated administration of morphine. It is suggested that the inhibitory effects
      of glycine might be mediated by dopaminergic (DAergic) transmission. Accordingly,
      the inhibition by glycine of the morphine-induced hyperactivity, reverse
      tolerance and dopamine receptor supersensitivity suggests that glycine might be
      useful for the treatment of morphine addiction.

PMID- 14723344
TI  - Differential regulation of cytochrome P450 isozyme mRNAs and proteins by femur
      fracture trauma.
AB  - The aim of this study was to investigate the effect of trauma on cytochrome P450
      (CYP) gene expression and to determine the role of Kupffer cells in trauma
      induced alteration of CYP isozymes. Rats underwent closed femur fracture (FFx)
      with associated soft-tissue injury under anesthesia. To deplete Kupffer cells in
      vivo, gadolinium chloride (GdCl3) was intravenously injected at 7.5 mg/kg body
      wt., 1 and 2 days prior to FFx surgery. At 72 h of FFx, liver tissues were
      isolated to determine the mRNA and protein expression of CYP isozymes and NADPH
      P450 reductase by reverse transcription-polymerase chain reaction and Western
      immunoblotting, respectively. In addition, the mRNA levels of tumor necrosis
      factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and heme
      oxygenase-1 (HO-1) were evaluated. FFx increased the mRNA level of CYP1A1; an
      increase that was not prevented by GdCl3. There were no significant differences
      in the mRNA expression of CYP1A2, 2B1 and 2E1 among any of the experimental
      groups. The protein levels of CYP2B1 and 2E1 were significantly decreased by FFx;
      a decrease that was not prevented by GdCl3 treatment. The gene expression of
      NADPH-P450 reductase was unchanged by FFx. FFx significantly increased the
      expression of TNF-alpha mRNA; an increase that was attenuated by GdCl3. The mRNA
      expression of HO-1 was increased by FFx, but not by GdCl3. Our findings suggest
      that FFx differentially regulates the expression of CYP isozyme through Kupffer
      cell-independent mechanisms.

PMID- 14723345
TI  - Immunomodulatory activity of betulinic acid by producing pro-inflammatory
      cytokines and activation of macrophages.
AB  - Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has
      been reported to be a selective inducer of apoptosis in various human cancer and
      shown anti-inflammatory and immunomodulatory properties. We postulated that BA
      modulates the immunomodulatory properties at least two groups of protein
      mediators of inflammation, interleukin-1beta (IL-1beta) and the tumor necrosis
      factor-alpha (TNF-alpha) on the basis of the critical role of the monocytes and
      tissue macrophages in inflammatory and immune responses. TNF-alpha and IL-1beta
      were produced by BA in a dose dependent manner at concentration of 0.625 and 10
      microg/mL. The production of NO associated with iNOS was inhibited when treated
      with LPS at the concentration of 2.5 to 20 microg/mL of BA whereas COX-2
      expression was decreased at 2.5 to 20 microg/mL. These modulations of
      inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and
      peritoneal macrophages. The morphology of macrophage was also examined and
      enhanced surface CD 40 molecule was expressed when treated BA at 0.625 to
      approximately 5 microg/mL with or without LPS. Furthermore, BA (20 microg/mL)
      enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results
      indicated that BA induced activation of macrophage and pro-inflammatory
      cytokines. This may provide a molecular basis for the ability of BA to mediate
      macrophage, suppress inflammation, and modulate the immune response.

PMID- 14723346
TI  - Enhanced liver targeting by synthesis of N1-stearyl-5-Fu and incorporation into
      solid lipid nanoparticles.
AB  - To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5
      Fu), it was acylated by stearyl chloride to obtain N1-stearyl-5-Fu (5-FuS). The
      chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and
      Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles
      (SLN), which were prepared by the physical agglomeration method. The mean
      diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release
      characteristics in vitro of 5-FuS-SLN were fitted to the first-order
      pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution
      of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in
      mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown
      as follows: Vd=0.04336 L/kg, T(1/2) beta=1.2834 h, CL=0.1632 L/h. In conclusion,
      5-FuS-SLN has significant liver targeting properties. The employment of a prodrug
      to enhance drug liposoluble properties and the preparation method presented in
      this paper, seem to be an alternative strategy to the traditional colloidal
      delivery system.

PMID- 14723347
TI  - Enhancement of heparin and heparin disaccharide absorption by the Phytolacca
      americana saponins.
AB  - We studied the effects of phytolaccosides, saponins from Phytolacca americana, on
      the intestinal absorption of heparin in vitro and in vivo. The absorption
      enhancing activity of these compounds (phytolaccosides B, D2, E, F, G and I) was
      determined by changes in transepithelial electrical resistance (TEER) and the
      transport amount of heparin disaccharide, the major repeating unit of heparin,
      across Caco-2 cell monolayers. With the exception of phytolaccoside G, all of
      them decreased TEER values and increased the permeability in a dose-dependent and
      time-dependent manner. In vitro, phytolaccosides B, D2, and E showed significant
      absorption enhancing activities, while effects by phytolaccoside F and I were
      mild. In vivo, phytolaccoside E increased the activated partial thromboplastin
      time (APTT) and thrombin time, indicating that phytolaccoside E modulated the
      transport of heparin in intestinal route. Our results suggest that a series of
      phytolaccosides from Phytolacca americana can be applied as pharmaceutical
      excipients to improve the permeability of macromolecules and hydrophilic drugs
      having difficulty in absorption across the intestinal epithelium.

PMID- 14723348
TI  - Synthesis and antiviral evaluation of novel 3'- and 4'-doubly branched
      carbocyclic nucleosides as potential antiviral agents.
AB  - A series of 3'- and 4'-branched carbocyclic nucleosides 25, 26, 27, 28, 29 and 30
      were synthesized starting from simple acyclic ketone derivatives. The
      construction of the required quaternary carbon was made using a [3,3]-sigmatropic
      rearrangement. In addition, the installation of a methyl group in the 3'-position
      was accomplished using a Horner-Wadsworth-Emmons (HWE) reaction with triethyl 2
      phosphonopropionate. Bis-vinyl was successfully cyclized using a Grubbs' catalyst
      (II). Natural bases (adenine, cytosine, uracil) were efficiently coupled with the
      use of a Pd(0) catalyst.

PMID- 14723349
TI  - Staphylococcus aureus bacteremia: compliance with standard treatment, long-term
      outcome and predictors of relapse.
AB  - The long-term outcome of compliance with standard treatment recommendations for
      Staphylococcus aureus bacteremia was assessed. Cases of S. aureus bacteremia at
      our institution over a 2-y period were reviewed and follow-up performed by review
      of subsequent admissions or contact with primary care physicians. We encountered
      226 cases (age 64.7 +/- 15.8 y) and most (171/226, 75.7%) had no removable
      source. In-hospital mortality rate was 32.7% (74/226). Follow-up of 104/152
      (68.4%) survivors (for 386.7 +/- 449.8 d) revealed 23.1% (24/104) relapses:
      recurrent bacteremia (n = 19), distant site (n = 3) and local recurrence (n = 2).
      Most relapses (21124; 87.5%) occurred within 90 d of therapy. Relapse rate was
      higher with vancomycin treatment (20148 vs. 4/56; p < 0.001), bacteremia for > or
      = 3 d (9/20 vs. 15/84; p = 0.001), and failure to remove the source (6/7 vs.
      6/22; p = 0.006). Vancomycin effect was independent of oxacillin susceptibility.
      Treatment for less than the standard 2-week duration among 19 patients with short
      duration of bacteremia (< 3 d) did not increase relapse rate (1/19; 5.3%).
      Duration of bacteremia, vancomycin therapy and failure to remove the source were
      predictors of relapse. Prospective studies are needed to determine if S. aureus
      bacteremias of short duration can be treated for 2 weeks or less, and define the
      optimal duration for prolonged bacteremia when vancomycin is used.

PMID- 14723350
TI  - Circulating tuberculostearic acid in tuberculosis patients.
AB  - Tuberculostearic acid (TBSA), a mycobacterial cell wall constituent, was measured
      in plasma samples using a highly sensitive high-performance liquid chromatography
      method. Plasma TBSA concentrations in patients with active tuberculosis (20 [0.5
      347] nmol/l; n = 125) were higher than in patients with a variety of non
      tuberculous pulmonary and extrapulmonary inflammatory conditions (0.1 [0-29]
      nmol/l; n = 116) and in healthy controls (0 [0-2] nmol/l; n = 102) (p = < 0.001).
      The calculated sensitivity, specificity, positive and negative predictive values
      for tuberculosis were 95.2%, 87.9%, 89.5% and 94.4%, respectively, indicating
      that assay of plasma TBSA might be a valuable complementary diagnostic tool.

PMID- 14723351
TI  - Overt and cryptic miliary tuberculosis misdiagnosed until autopsy.
AB  - Autopsy confirmed deaths due to miliary tuberculosis in Finland were analysed in
      order to improve the diagnosis of the disease. Tuberculosis deaths from mortality
      statistics were examined in order to identify miliary tuberculosis deaths, and
      the medical records of the autopsied cases were studied. The deceased were
      divided into 2 groups, 'overt' disease and 'cryptic' disease, on the basis of
      chest X-ray findings. There were 114 overt (mean age 79 y) and 140 cryptic (mean
      age 78 y) miliary tuberculosis cases. The majority of patients in both groups
      were females. There was no difference between the groups in history of previous
      tuberculosis, in predisposing factors or in symptoms. Suspicion of tuberculosis
      was recorded before death in 86% in overt form and in 53% in cryptic form. In
      overt disease 50% of the patients received chemotherapy, but in cryptic form only
      a quarter were treated. In one third of cases autopsy had been carried out
      without suspicion of tuberculosis. Suspicion of tuberculosis had arisen too
      seldom, especially in the cryptic group. On the other hand, those suspected to
      have tuberculosis were not promptly treated with the appropriate chemotherapy.
      Absence of suspicion and delayed diagnosis mean increased risk in health care and
      at autopsy.

PMID- 14723352
TI  - Multifocal skeletal tuberculosis in children: a retrospective study of 18 cases.
AB  - Multifocal skeletal tuberculosis is an uncommonly reported entity, Unanimity on
      terminology is lacking in the literature. The article presents a series of 18
      such patients encountered in our institution. All the patients were below 15 y of
      age. Male to female ratio was 13:5. Most of the cases presented with swellings,
      discharging sinuses and/or ulcers. Appendicular involvement was seen in 17 of
      these cases. All the cases were diagnosed histopathologically as tuberculosis.
      All the cases were treated with multi-drug anti-tubercular therapy with
      additional procedures such as incision and drainage or sinus tract curettage
      performed in 9 of the patients. All the lesions healed. Their clinical behaviour,
      result and outcome are analysed with available international literature.

PMID- 14723353
TI  - Prevalence of drug resistance mutations and non-B subtypes in newly diagnosed HIV
      1 patients in Denmark.
AB  - The aim of this study was to monitor the prevalence of drug resistance mutations
      in newly diagnosed HIV-1 positive individuals in Denmark. In addition we assessed
      the prevalence of non-B subtypes based on phylogenetic analysis of the pol gene.
      Plasma samples from 104 newly diagnosed HIV-1 positive patients were obtained in
      the year 2000. The entire protease gene and 320 amino acids of the reverse
      transcriptase gene were genotyped. Sequences were obtained from 97 patients. No
      subjects displayed primary resistance mutations in the protease gene, whereas all
      carried 1 or more secondary mutations. Resistance mutations in the RT-gene
      associated with NRTI-resistance were found in 1 patient, who was infected with
      zidovudine resistant HIV-1 harbouring the M41L mutation in combination with T215S
      and L210S. The T215S mutation has been showed to be associated with reversion of
      zidovudine resistance. The T215S mutation was found in 1 additional patient. The
      subtype distribution was subtype B 59%, C 18%, A 8%, CRF02_AG 5%, CRF01_AE 4%, D
      3% and G 2%. We found 2 patients (2%) with mutations associated with resistance
      in the RT-gene and none in the protease gene indicating a low prevalence of
      resistant HIV-1 in Denmark in the year 2000.

PMID- 14723354
TI  - New aspects on the natural history of chronic hepatitis B infection: implication
      for therapy.
AB  - The incidence and sequelae of chronic hepatitis B (HBV) infection appear to have
      been overestimated previously, especially in areas outside Asia where neonatal
      infection predominates. A high rate of spontaneous HBeAg seroconversion is found
      in children as well as adults, and 40 to 50 y of replicative infection seems to
      be the most important risk factor for cirrhosis and hepatocellular carcinoma
      necessitating a cautious attitude towards antiviral treatment. Of concern,
      however, HBeAg seroconversion, which usually predicts a good outcome, is not
      always an irreversible event. Low grade replication of HBV may continue in anti
      HBe positive individuals and shift in HBe status does occur in up to 10% of viral
      carriers with evidence of an increased risk of complications. Viral replication
      (HBV DNA positivity) is also found in HBeAg negative mutant infection and is an
      important parameter to note. To date, the data do not suggest any different
      prognosis for patients with this kind of infection. Also the various viral
      genotypes might have different prognoses partly due to the association with
      precore mutations, but the present knowledge does not allow different therapeutic
      management as in the case of hepatitis C. Treatment is available with a number of
      safe antiviral agents. However, all of them are mainly suppressive with low cure
      rates after 1 y. Initiation of therapy should therefore mainly be considered in
      symptomatic chronic infection and in cases with high risk of complications i.e.
      patients with ongoing viral replication and age above 40 y or bridging necroses
      verified by liver biopsy.

PMID- 14723355
TI  - Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical
      transmission.
AB  - Little is known about how pregnancy influences viremia levels in women with
      chronic hepatitis B virus infection. In this study, we first retrospectively
      analysed changes in HBV DNA levels during and after 55 pregnancies in HBsAg
      positive women, of whom 9 were HBeAg-positive. Secondly, HBV DNA levels in 3
      HBeAg-positive mothers whose babies became chronic HBV carriers, were compared
      with levels in 18 mothers whose babies were not infected by HBV. We found that
      HBV DNA ranged from 10(8.1) to 10(9.5) copies/mL in HBeAg-positive, and from
      undetectable (< 100) to 10(6.8) copies/mL in HBeAg-negative mothers. HBV DNA
      increased by a mean of 0.4 log late in pregnancy or early post partum; in 4 out
      of 16 HBeAg negative mothers by > 1 log during pregnancy. Post partum ALT
      increased in both HBeAg-positive and negative women. HBV DNA was 10(9.4)-10(10.4)
      copies/mL in 3 HBeAg-positive mothers whose babies were, as compared to < 100
      10(10.4) copies/mL in 18 whose babies were not, vertically infected. Although the
      majority of HBeAg-negative women had low and relatively stable HBV DNA during
      pregnancy, viremia was also relatively high in some HBeAg-negative mothers, and
      both viremia and ALT increased significantly late in pregnancy or shortly after
      delivery. Vertical transmission was only seen in HBeAg-positive mothers with very
      high levels of viremia. The value of measuring HBV DNA in the pregnant woman to
      modify immunoprophylaxis to her infant needs further study.

PMID- 14723356
TI  - Death from the Nile crosses the Atlantic: the West Nile Fever story.
AB  - The present paper reviews the American epidemic of West Nile Fever (WNF), which
      is the largest recorded outbreak ever. The epidemiological consequences of
      introducing a novel and immunologically unknown pathogen in a previously
      unexposed population and the possible evolution of a more pathogenic viral strain
      are discussed. In view of recent reports of imported cases in Denmark the issue
      of possible disease spread to Scandinavia is likewise addressed. However, the
      main scope of the article is to provide the clinician with an overview of the
      natural history, epidemiology and clinical characteristics of the disease.

PMID- 14723357
TI  - Characterization of Leishmania chagasi DNA topoisomerase II: a potential
      chemotherapeutic target.
AB  - DNA topoisomerase II (topo II), an enzyme essential for cellular replication, is
      an eminent target for antimicrobial therapy against Leishmania chagasi, the major
      cause of visceral leishmaniasis in Latin America. The complete L. chagasi (Lch)
      TOP2 gene, encoding L. chagasi topo II, was isolated from genomic DNA using the
      polymerase chain reaction. The LchTOP2 gene revealed an open reading frame (ORF)
      of 3,711 base pairs predicting a protein with 1,236 amino acids and an estimated
      molecular weight of 140 kDA. The L. chagasi topo II sequence had high identity
      with the L. donovani topo II (98.8%) and L. infantum topo II (98.7%), followed by
      Crithidia fasciculata topo II (84.4%), Trypanosoma cruzi topo II (67.6%) and
      Trypanosoma brucei topo II (66.6%). Lch topo II had low identity with the human
      homologs htopo II alpha (26.3%) and htopo II beta (26.4%). Differences between L.
      chagasi TOP2 and human TOP2 genes suggest that leishmanial topo II is a potential
      target for the development of new antileishmanial agents.

PMID- 14723358
TI  - A population-based case-control teratological study of oral nystatin treatment
      during pregnancy.
AB  - The aim of the study was to investigate the teratogenicity of oral nystatin
      treatment during pregnancy in the population-based data set of the Hungarian Case
      Control Surveillance of Congenital Abnormalities between 1980 and 1996. In total,
      38,151 pregnant women who delivered newborn infants without any defects (control
      group) and 22,843 pregnant women who had foetuses or newborns with congenital
      abnormalities (CA) (case group) were included in the study. 106 (0.5%) case and
      143 (0.4%) control pregnant women were treated with oral nystatin (crude OR with
      95% CI = 1.2, 1.0-1.6). A teratogenic potential of nystatin was seen in 1 CA
      group (hypospadias) in 2 different approaches of the study (case-control and
      total control--CA groups comparison) during the critical period of this
      congenital abnormality. The conclusion of the study is that treatment with oral
      nystatin during pregnancy presents little teratogenic risk to the foetus, but the
      possible association between hypospadias and nystatin needs further study.

PMID- 14723359
TI  - Weekly antibiotic prescribing and influenza activity in Sweden: a study
      throughout five influenza seasons.
AB  - Influenza often leads to bacterial complications that require treatment. It may
      also be confused with bacterial respiratory infections, leading to unnecessary
      prescription of antibiotics. In this first study on the relationship between
      influenza and antibiotic utilization for a whole country, weekly data on verified
      influenza cases in Sweden were compared to weekly sales of antibiotics for 5
      influenza seasons 1997-2002. The peak of influenza activity occurred during the
      winter. In 4 out of the 5 monitored influenza seasons it occurred in February
      March. The fluctuation of antibiotic utilization was relatively constant over the
      years with peaks before Christmas and in February-March. There were no obvious
      differences in the total amount of antibiotics dispensed over the years that
      could be related to influenza activity, but a coincidental relationship between
      the peaks of diagnosed influenza cases and the peaks of antibiotic utilization
      was indicated, especially for older age groups.

PMID- 14723360
TI  - Antibiotic consumption, bacterial resistance and their correlation in a Swiss
      university hospital and its adult intensive care units.
AB  - Ecological surveys of high-antibiotic use areas in the hospital should be used to
      evaluate patterns and trends in order to optimise antibiotic consumption and
      minimise resistance. We conducted a retrospective cohort study with the aim to
      examine trends in antimicrobial consumption and bacterial susceptibility at the
      Geneva University Hospital and its adult ICUs between 1996 and 2000. The average
      annual consumption of antimicrobials was 400 d-defined doses (DDD)/1000 patient-d
      in the entire hospital, 462 in the surgical ICU and 683 in the medical ICU. In
      the medical ICU, we observed a steady decrease of intravenous antimicrobial use,
      whereas a 25% increase in the total antimicrobial consumption was noted in 1999
      and 2000 for the entire hospital. The proportion of different bacterial species,
      resistance rates and antibiotic consumption rates differed between the entire
      hospital and the ICUs, with moderate variation between y. Possible relationships
      between antibiotic consumption and resistance rates, expressed as DDD and as
      number of resistant isolates per 1000 patient-d respectively, were calculated for
      of the most frequently isolated bacteria (total 71 correlations). Statistically
      significant positive correlations between antibiotic consumption and resistance
      were found in Escherichia coli for piperacillin, in Pseudomonas aeruginosa for
      piperacillin, cephalosporins and aminoglycosides, in Klebsiella spp. for
      cephalosporin, in coagulase-negative staphylococci for gentamicin and in
      Streptococcus pneumoniae for penicillin.

PMID- 14723361
TI  - Impact of conventional chemotherapy on levels of antibodies against vaccine
      preventable diseases in children treated for cancer.
AB  - Intensive chemotherapy in children with malignancies causes partial immune
      deficiency, including long-term impairment of humoral immunity. We investigated
      the levels of antibodies against measles, mumps, polio, rubella, diphtheria,
      tetanus, and Haemophilus type b (Hib) in 139 children at the time of diagnosis of
      the malignant disease, during chemotherapy, after cessation of intensive
      treatment, and after re-vaccination. In general, cytostatic therapy resulted in a
      significant lowering of antibody levels. A decline of antibodies below the
      protective level as a consequence of cytostatic treatment was observed in 6% of
      the children for measles and mumps, in 18%, 12%, and 25% for polio types 1, 2,
      and 3, and in 21% for diphtheria. By contrast, rubella and tetanus antibodies
      remained within the protective range in all cases of this study. Re-vaccination 3
      to 5 months after cessation of chemotherapy produced antibody levels about as
      high as those measured prior to therapy. Only 6 out of 83 children with
      previously positive antigen titres did not respond to re-vaccination. Vaccination
      or re-vaccination failed in 5 of 13 non-responders for more than 1 antigen,
      indicating a decreased reactability to vaccinations in some patients.

PMID- 14723362
TI  - High hepatocyte growth factor levels in faeces during acute infectious
      gastroenteritis.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen of mature epithelial cells
      which is produced after organ injuries and acts as a trigger for regeneration in
      the impaired organ. The aim of the present study was to investigate local
      production of HGF during infectious gastroenteritis. We measured the
      concentration of HGF in serum and faeces in 49 patients with acute infectious
      gastroenteritis (bacterium = 30, virus = 10, amoebae = 1, and probable infection
      = 8) at the time of referral to hospital and at convalescence (n = 31). The
      values were compared with normal healthy vaccination volunteers (n = 11) as well
      as patients with acute non-infectious diarrhoea (n = 10). The presence of HGF in
      faeces was confirmed by ELISA and Western immunoblot. HGF concentrations in
      faeces was significantly higher in the patients with infectious gastroenteritis
      compared to the control groups (p < 0.0001). Using a cut-off concentration of 20
      ng/g, the overall sensitivity of faeces HGF to distinguish infectious
      gastroenteritis (bacterial, viral, probable infection) was 98% with a specificity
      of 100%. At convalescence all patients had normal values. There was no
      significant correlation between HGF concentrations in faeces and serum.
      Determination of faeces HGF may identify cases of transmittable diarrhoea
      requiring isolation at an early stage.

PMID- 14723364
TI  - Human leptospirosis in Bulgaria, 1989-2001: epidemiological, clinical, and
      serological features.
AB  - A total of 455 confirmed and reported to the Bulgarian Ministry of Health
      leptospirosis cases between 1989 and 2001 were analysed. Overall incidence of the
      disease was 0.42/100.000 population (range 0.20-0.64/100.000). The overall
      fatality rate was 6.6%. Infection was acquired through occupational (30.3%),
      recreational (45.1%), and accidental (4.6%) exposure or was home contracted
      (5.1%). A tendency towards the main mode of transmission moving from occupational
      to recreational exposure was noted. Fishing and livestock farming together
      accounted for more than half of all leptospirosis cases. Leptospirosis was
      contracted more frequently through indirect contact with animal excreta and less
      commonly through direct contact with animal urine or tissue. Serovars belonging
      to 10 different serogroups caused infection during the 13-year study period. Two
      serogroups, Icterohaemorrhagiae and Pomona, accounted for more than 87% of all
      leptospirosis cases. The third main cause was serogroup Australis. The
      significant change in the infecting serovars has to be related to widely
      performed vaccinations of cattle and pigs but still inefficient measures for
      rodent control. The most frequently reported symptoms were fever, myalgia,
      jaundice, and hepatomegaly. Anicteric cases (40.3%) had milder flu-like course.
      Acute renal failure was reported in 52 (33.8%) of the patients, all of them with
      icteric leptospirosis. Knowledge of epidemiological, clinical, and serological
      features of leptospirosis in Bulgaria during the 13-year study period is an
      appropriate base to outline measures for successful prevention and early
      diagnosis of the disease.

PMID- 14723363
TI  - Molecular epidemiology of tuberculosis in Slovenia: results of a one-year (2001)
      nation-wide study.
AB  - Slovenia is a small Central European country with a population of 1.99 million
      and an incidence of tuberculosis (TB) of 18.6 per 100,000 inhabitants in 2001. In
      a prospective nation-wide, 1-y DNA fingerprinting study, the genetic diversity of
      99.7% of all Mycobacterium tuberculosis isolates obtained from Slovenian patients
      with culture-verified TB in 2001 were assessed using a standardized IS6110
      restriction fragment length polymorphism (RFLP) method. Among 306 M. tuberculosis
      isolates, 228 different IS6110 RFLP patterns were found. The number of IS6110
      copies varied from 2 to 16 (9.2 copies per isolate on average). Only 2 isolates
      (0.7%) with less than 5 IS6110 copies were identified. Clustered M. tuberculosis
      isolates were detected in 116 (37.9%) patients. The degree of recent transmission
      in the 1-y period was 25%. The clustering rate decreased with age from 46.4% (age
      group under 35 y) to 19.5% (age group above 65 y). A history of alcohol abuse and
      homelessness was found to be associated with clustering of TB cases. In
      conclusion, a high clustering frequency was identified among Slovenian TB
      patients. The study increased our understanding of important risk factors and
      routes of TB transmission in Slovenia.

PMID- 14723365
TI  - Three cases of viridans group streptococcal bacteremia in children with febrile
      neutropenia and literature review.
AB  - Three cases of viridans group streptococcal bacteremia in 2 children with brain
      tumours and in 1 with autoimmune neutropenia are presented. All children were
      neutropenic. The 2 patients with malignancy also had mucositis. The isolated
      strains of viridans group streptococci showed considerable resistance to
      antibiotics. All patients were empirically treated with third generation
      cephalosporins and amikacin, before antibiotic sensitivities were available and
      recovered without complications. Viridans group streptococcal bacteremia should
      be suspected in neutropenic children, especially in the presence of mucositis.
      Prospective, randomized clinical trials of mouth antiseptics are needed to
      clarify the usefulness, if any, of such measures in the reduction of viridans
      group streptococcal bacteremia in this group of patients.

PMID- 14723366
TI  - Streptococcus pyogenes meningitis complicating varicella in a 3-month-old child.
AB  - Varicella is a common, usually self-limited infectious disease, and complications
      are believed to be rare. Despite the dramatic increase in invasive Streptococcus
      pyogenes infections associated with varicella zoster virus infections in recent
      years, post-varicella S. pyogenes meningitis occurs very rarely. The third case
      in the literature is described here.

PMID- 14723367
TI  - Group B streptococcal necrotizing fasciitis and toxic shock-like syndrome: a case
      report and review of the literature.
AB  - We report the fourth case of group B streptococcal (GBS) necrotizing fasciitis
      and toxic shock-like syndrome. Since the mechanism of GBS toxic shock may be
      similar to Group A Streptococcus, intravenous immunoglobulin should be considered
      as an adjunct to clindamycin-based antibiotic therapy.

PMID- 14723368
TI  - Chryseobacterium indologenes bacteremia in a bone marrow transplant recipient
      with chronic graft-versus-host disease.
AB  - We describe a case of Chryseobacterium indologenes bacteremia in a leukemia
      patient with chronic graft-versus-host disease (GVHD) 6 months after allogeneic
      bone marrow transplantation. Blood cultures from a vein and via Hickman catheter
      grew C. indologenes. The patient was successfully treated with
      piperacillin/tazobactam and the infection did not recur. Our case indicates that
      C. indologenes infection can occur in patients with GVHD after allogeneic BMT and
      might be treated with a single agent, piperacillin/tazobactam without the removal
      of intravascular catheter.

PMID- 14723369
TI  - Clostridium perfringens pleuropulmonary infection and septic shock: case report
      and population-based laboratory surveillance study.
AB  - We report a rare case of necrotizing pneumonia, empyema, and septic shock caused
      by Clostridium perfringens. Population-based laboratory surveillance was
      subsequently conducted that identified an annual incidence of invasive C.
      perfringens disease of 0.83 per 100,000 population with a striking age-related
      increased risk for acquisition.

PMID- 14723370
TI  - Facial paralysis and meningitis caused by Rickettsia typhi infection.
AB  - Involvement of cranial nerves was rarely reported in various rickettsioses. We
      present here for the first time a case of peripheral facial paralysis associated
      with Rickettsia typhi infection.

PMID- 14723371
TI  - Tuberculosis presenting as epitrochlear lymphadenitis.
AB  - Epitrochlear lymphadenitis is an uncommon presentation of extrapulmonary
      tuberculosis in an immunocompetent host. This case report describes the third
      case in the literature and provides a review of the literature.

PMID- 14723372
TI  - Spondylodiscitis due to Aerococcus urinae: a first report.
AB  - Aerococcus urinae is an uncommon urinary tract pathogen which causes infections
      predominantly in elderly persons with local and general predisposing conditions.
      There are few case reports of severe infections caused by Aerococcus urinae among
      which only 14 cases of endocarditis caused by Aerococcus urinae have been
      reported. We report the first case of Aerococcus urinae spondylodiscitis. The
      patient responded to 4 weeks of amoxicillin and clindamycin, and to 5 months of
      amoxicillin alone.

PMID- 14723373
TI  - Unsuccessful treatment with voriconazole of a brain abscess due to
      Cladophialophora bantiana.
AB  - Cladophialophora bantiana is a dematiaceous fungus, associated with brain abscess
      in normal or immunosuppressed patients. We report a case of CNS infection in this
      agent unsuccessfully treated by surgery and various antifungal compounds
      including high doses of voriconazole (6 mg/kg bid). No adverse effects related to
      this compound were observed.

PMID- 14723374
TI  - Co-administration of caspofungin and cyclosporine to a kidney transplant patient
      with pulmonary Aspergillus infection.
AB  - A kidney transplant patient on cyclosporine treatment developed focal pneumonia
      due to Aspergillus fumigatus. The patient was not able to tolerate amphotericin B
      deoxycholate and was switched to caspofungin. The patient responded favourably
      without any evidence of toxicity from concomitant use of caspofungin and
      cylosporine.

PMID- 14723375
TI  - Fusarium osteomyelitis of the foot in a patient with diabetes mellitus.
AB  - Diabetic foot osteomyelitis is among the most common and serious complications in
      patients with diabetes mellitus. It is often a polymicrobial infection. We report
      the first case of foot osteomyelitis in a diabetic patient caused by Fusarium
      solani.

PMID- 14723376
TI  - Atovaquone/proguanil resistance in Africa: a case report.
AB  - The Atovaquone/proguanil combination has quickly been established as an effective
      chemoprophylaxis for travellers to areas with chloroquineresistant Plasmodium
      falciparum malaria. We describe the molecular cause of the first reported case of
      primary Atovaquone/proguanil resistance observed in our department in a
      Plasmodium falciparum infected traveller returning from West Africa, and link our
      findings to other reports of resistance.

PMID- 14723377
TI  - Eosinophilic meningitis following incomplete resection of a meningeal hydatid
      cyst.
AB  - Cerebral hydatid cyst is a rare complication of cystic echinococcosis (CE), but
      is associated with substantial mortality and morbidity. The case is described of
      a patient presenting with cerebral CE, complicated by a postoperative
      eosinophilic meningitis which resolved under corticosteroids. The therapeutic
      options for cerebral CE are discussed.

PMID- 14723378
TI  - An unusual cause of acute respiratory distress in a patient with AIDS: primary
      infection with Toxoplasma gondii.
AB  - Hypoxemic pneumonia in AIDS patients is mainly caused by Pneumocystis carinii,
      Toxoplasma gondii and CMV, although the significance of CMV recovery in BALF is
      often unclear. Since lung involvement generally occurs during reactivation, T.
      gondii is not expected to be demonstrated in patients without evidence of past
      infection with this agent. We report a fatal case of pneumonia revealing a T.
      gondii primary infection diagnosed thanks to the PCR analysis of the BALF.

PMID- 14723379
TI  - Cytomegalovirus-induced haemorrhagic cystitis in a patient with neurogenic
      bladder.
AB  - We report a case of severe cytomegalovirus induced haemorrhagic cystitis
      associated with neurogenic urinary bladder in a patient suffering from anaplastic
      spinal ependymoma. The diagnosis was established by bladder biopsy and
      immunohistochemical study. Haematuria resolved after ganciclovir therapy.
      Previous reports are reviewed.

PMID- 14723380
TI  - A case of severe CMV-colitis in an HIV positive patient despite moderate
      immunodeficiency.
AB  - CMV-colitis is rare in HIV positive patients with CD4 counts higher than 100
      microl(-1). We report a patient who was suffering from extensive CMV-colitis
      despite modest immune defect. The diagnosis was confirmed by repeated biopsies.
      The patient experienced an unusually long recovery which was only achieved after
      initiation of HAART.

PMID- 14723381
TI  - Mixed arterial and venous thromboembolism in a person with HIV infection.
AB  - People with human immunodeficiency virus (HIV) infection are more susceptible to
      thromboembolic events. Venous thromboembolism (VTE) occurs frequently in HIV
      infected persons but arterial thrombosis has only rarely been reported. We
      describe a case of a person with HIV infection who developed an arterial
      thrombosis and 3 months later an extensive VTE. Several non-HIV and HIV related
      thrombogenic factors were identified.

PMID- 14723382
TI  - Progressive multifocal leukoencephalopathy in a patient with X-linked
      agammaglobulinemia.
AB  - To our knowledge, this is the first case report describing progressive multifocal
      leukoencephalopathy (PML) associated with X-linked agammaglobulinemia. The JC
      virus was confirmed at autopsy and PML was diagnosed. Humoral immunodeficiency
      with normal cellular immunity could be infected with JCV.

PMID- 14723383
TI  - Facial erysipelas after receiving acupuncture treatment.

PMID- 14723384
TI  - Ochrobactrum anthropi bacteraemia.

PMID- 14723385
TI  - Hepatopulmonary masses after eating Romaine lettuce.

PMID- 14723386
TI  - Penicillin resistance in viridans streptococcal bacteremia is related with high
      mortality.

PMID- 14723387
TI  - The obesity epidemic: contextual influences on physical activity and body weight.

PMID- 14723388
TI  - Recognition of left ventricular hypertrophy in new recruits of professional sumo
      wrestling.
AB  - The efficacy of electrocardiography (ECG) in the diagnosis of left ventricular
      (LV) hypertrophy in 890 males, newly recruited to Japanese professional sumo
      wrestling (15.9 +/- 1.8 years of age, 177.8 +/- 4.7cm, 107.3 +/- 4.7kg), was
      tested by comparing simple, widely employed ECG criteria (Sokolow-Lyon chest and
      limb lead voltages and Cornell voltage with repolarisation criteria) with
      echocardiographic evaluations of LV mass indexed to body surface area. LV
      hypertrophy was defined as a LV mass index > 2 SD above the mean value obtained
      from 115 age-matched, normotensive, sedentary, male controls. The prevalence of
      LV hypertrophy as determined by echocardiography was 9.0% the entire group and
      was 8.3% among the 484 normotensives. The sensitivities of the three ECG criteria
      were < or = 36.0%, and their specificities were 70.0-99.0%. In contrast to the
      Sokolow-Lyon chest lead criteria, the diagnostic performance of the Cornell
      criteria was little affected by body mass index (BMI), and stepwise regression
      revealed that BMI did not significantly correlate with Cornell voltage. Still,
      the diagnostic efficacy of ECG was not sufficient to merit its use for primary
      recognition of LV hypertrophy among professional sumo wrestlers. Indeed, LV
      hypertrophy will likely go undetected by ECG in most overweight muscular
      athletes.

PMID- 14723389
TI  - The effects of anabolic-androgenic steroids upon resting and peak exercise left
      ventricular heart wall motion kinetics in male strength and power athletes.
AB  - Previous investigations reported alterations in myocardial fibres and systolic
      function associated with anabolic-androgenic steroid consumption by athletes.
      Advances in bio-medical technology have allowed further investigation in
      assessing the possible effects of anabolic-androgenic steroids on gross left
      ventricular kinetics. Twenty-three male strength and power athletes with a past
      and current history of anabolic-androgenic steroid consumption (x 46 days, range
      28 days to 70 days), were compared to 23 controls. Testing consisted of resting
      and immediate post-exercise transthoracic left ventricular wall cardiokymograms.
      Statistical results identified no difference over time between groups or
      condition. Cardiokymographic waveform analysis found 32.61% of all (n =184)
      waveforms to be abnormal (Type II, n = 56 or Type III, n = 4). There were 14
      treatment subjects (60.87%) who demonstrated an abnormal waveform as compared to
      9 controls (39.13%). A significant difference (p < or = 0.01) in the overall
      proportions of waveform types was identified where the treatment group exhibited
      41.30% abnormal waveforms, compared to 23.91% by controls. Additionally, two
      athletes (1 treatment, 1 control) demonstrated abnormal left ventricular wall
      motions (Type III) analogous to impaired left ventricular performance. The
      results indicated: (a) highly strength trained athletes with no history of
      anabolic-androgenic steroid usage exhibited an unexpected high incidence of Type
      II waveforms (28.26% pre/23.91% post); (b) a comparable group of strength trained
      athletes using anabolic-androgenic steroids exhibited a significantly higher
      percentage of abnormal waveforms as compared to controls (34.78% pre/37.21%
      post). Based on these results, high intensity strength training with and without
      anabolic-androgenic steroid supplementation induced alterations in the left
      ventricular wall motion.

PMID- 14723390
TI  - Occupational physical activity across occupational categories.
AB  - This study investigated the amount of physical activity that occurs during normal
      working hours, highlighting the occupational differences in physical activity by
      occupational category. Data were collected by means of a self-administered
      questionnaire (Tecumseh Occupational Physical Activity Questionnaire [TOQ]),
      which measures past year Occupational Physical Activity (OPA) and by a motion
      sensing device (Yamax DigiWalker Pedometer SW - 700). Ninety male and female
      participants aged 18-62 years participated in the study. Participants were
      stratified by occupational category according to the Australian Standard
      Classification of Occupations (ASCO), which was then condensed into professional,
      white-collar and blue-collar workers. The results showed significant (p < .05)
      increases in OPA from the professional category (least active) through to the
      blue-collar workers (most active) in terms of walking activity. Mean daily step
      counts were 2,835, 3,616 and 8,757 for professional, white-collar and blue-collar
      respectively. Occupational Physical Activity Scores and Work Activity Units (WAU)
      in MET - min x wk(-1) from the TOQ showed similar patterns, with blue collar
      reporting significantly (p < .05) more past year OPA than their white-collar and
      professional workers. Significant correlations were also shown between the
      pedometer (step-count data) and the TOQ (r = .38 - .74, p < .01).

PMID- 14723391
TI  - Effect of measuring blood lactate concentrations using different automated
      lactate analysers on blood lactate transition thresholds.
AB  - This study investigated the effect of using three automated blood lactate
      analysers (Accusport, Lactate Pro, YSI 1500 Sport) on blood lactate transition
      thresholds (BLTT). Blood lactate concentrations were measured using the three
      analysers in rowers (n = 17) and kayakers (n = 6) during incremental exercise.
      The BLTT determined were: 1) ADAPT lactate threshold (data point preceding
      lactate increase of > or = 0.4 mmol x l(-1)), 2) log-log lactate threshold (point
      of lactate increase when log lactate plotted against log of relevant exercise
      parameter), 3) DMAX anaerobic threshold, 4) ADAPT anaerobic threshold (modified
      DMAX method), 5) Onset of blood lactate accumulation (OBLA, fixed blood lactate
      concentration of 4 mmol x l(-1)). Measurements of blood lactate concentration
      differed between analysers (p < 0.0001), resulting in BLTT differing between
      analysers when expressed as a blood lactate concentration (p < 0.0001), or when
      the BLTT was defined as a fixed blood lactate concentration (e.g. OBLA) (p <
      0.0001). When expressed as a power output or heart rate using BLTT based on
      relative changes in lactate concentration (log-log, ADAPT and DMAX thresholds)
      the values were similar between analysers (p > 0.05), except the Accusport
      provided higher values for the log-log lactate threshold (p < 0.0001). We
      concluded that, despite providing significantly different lactate concentrations,
      unless the Accusport was used to determine the log-log lactate threshold, or
      values were expressed as a blood lactate concentration, the use of different
      analysers had little effect on the BLTT.

PMID- 14723392
TI  - Comparison of W(peak), VO2(peak) and the ventilation threshold from two different
      incremental exercise tests: relationship to endurance performance.
AB  - This report presents data comparing the peak rate of oxygen consumption
      (VO2(peak)), peak power output (W(peak)) and the ventilation threshold (VT)
      obtained from two different incremental cycle exercise tests performed by nine
      well trained triathletes (Mean +/- SD age 32 +/- 3 yrs; body mass 77.4 +/- 4.9 kg
      and height 185 +/- 3 cm). Furthermore, the relationship between these variables
      and the average sustained power output (W) during a 90 min cycle time trial (TT)
      was also determined. The two incremental exercise tests involved a 'short' test,
      which commenced at 150 W with 30 W increments every 60 s until exhaustion. The
      second ('long') incremental test commenced at a power output representing 50% of
      the W(peak) obtained in the short test. The subjects were then required to
      increase the power output by 5% every 3 min until exhaustion. The results showed
      the W(peak) (W) in the short test was significantly (p < 0.01) higher than in the
      long test. However, there was no significant difference in the VO2(peak) (1 x
      min(-1)) between the two tests. There was a weak but significant correlation
      between W(peak) (W) and VO2(peak) (l x min(-1)) (r = 0.72: p < 0.05) in the short
      (60 s stage) test but not the long (3 min stage) test (r = 0.52). There were no
      significant differences and good agreement between for the heart rate (HR) (b x
      min(-1)) and oxygen consumption (VO2) corresponding to the VT. In contrast, the
      power output (W) corresponding to the VT was significantly different and not
      comparable between the long and short incremental tests. The cycle TT performance
      was most correlated to the W(peak) (W) (r = 0.94; p < 0.01) and the VT (W) (r =
      0.75; p < 0.05) from the long test as well as the VO2(peak) (l x min(-1))
      obtained from the short incremental test (r = 0.75; p < 0.01). These data suggest
      that the length of stages during incremental cycle exercise may influence the
      W(peak) and in turn the relationship of this variable to VO2(peak). Furthermore,
      the W(peak) obtained from a test incorporating 3 min stage increments represents
      the best indicator of 90 min cycle performance in well-trained triathletes.

PMID- 14723393
TI  - Sleep quality responses to atmospheric variation: case studies of two elite
      female cyclists.
AB  - Strategies applied during sleep to potentially enhance athlete performance use
      different atmospheric conditions. High altitude conditions are known to affect
      sleep adversely but the effects of mild-moderate altitude and O2 enrichment at
      mild altitude are uncertain. We performed case studies using two elite female
      road cyclists (mass and maximal aerobic power of 62 kg, 65.8 ml x kg(-1) x min(
      1); 57 kg, 62.7 ml x kg(-1) x min(-1)) to examine changes in sleep for different
      atmospheric conditions applied throughout the preparation for, and during, an
      International Stage race. Conditions were: i) normoxia (600 m), ii) simulated
      moderate altitude (2650 m), iii) natural mild altitude (1380 m) and iv) O2
      enrichment at mild altitude (30% O2@ 1300-1500 m). We measured respiratory
      disturbances, arousals, number of awakenings, blood oxygen saturation (SpO2),
      heart rate (HR), rapid eye movement sleep (REM) and deep sleep. Respiratory
      disturbances, SpO2 and HR responses were similar for both cyclists for all
      conditions. Compared with normoxia, both cyclists had somewhat reduced REM at
      natural mild altitude and moderate simulated altitude but differed in their REM
      and deep sleep responses to O2 enrichment. Compared with mild altitude, both
      showed increased awakenings and deep sleep with O2 enrichment. Only one cyclist
      clearly increased her REM sleep with O2 enrichment compared to mild altitude. Our
      data highlight two different sleep quality responses to atmospheric variation.

PMID- 14723394
TI  - Test-retest reliability of the aerobic power index component of the tri-level
      fitness profile in a sedentary population.
AB  - Use of maximal aerobic power (VO2(max)) testing, which requires subjects to
      exercise to physiological limits, may deter eligible candidates from volunteering
      for trials and may also be contraindicated in patients suffering from various
      medical illnesses. An alternative to maximal testing is submaximal testing. The
      Aerobic Power Index, which represents the aerobic component of the Tri-level
      Fitness Profile, is a submaximal test that has been shown to be reliable in
      trained athletes. The purpose of this study was to establish reliability of the
      Aerobic Power Index, as well as associated variables of VO2 (ml x kg(-1) x min(
      1) and rate of perceived exertion (RPE), in a group of sedentary subjects.
      Results for the 20 subjects who participated in a test-retest trial indicated
      high reliability (ICC r = 0.98, %TEM 3.87 W x kg(-1); SEM 0.04 W x kg(-1) for the
      main measurement outcome of Watts per kilogram (W x kg(-1)). Oxygen uptake (ml x
      kg(-1)min(-1)) also demonstrated high reliability (ICC r = 0.92; %TEM 4.63 ml x
      kg(-1) x min(-1); SEM 0.58 ml x kg(-1) min (-1), as did RPE (ICC r = 0.97,%TEM
      7.78; SEM 0.63). Limits of agreement were -0.02+/-0.16 W x kg(-1). -0.41+/-2.31
      ml x kg(-1) x min(-1) for VO2 and -0.05 < or = 2.10 for RPE. These results
      indicate that the Aerobic Power Index is a reliable submaximal exercise test for
      use in sedentary subjects.

PMID- 14723395
TI  - Comparison of a footpad analyser with a tetrapolar model for the determination of
      percent body fat in young men.
AB  - Since excess weight in adolescence predisposes to overweight and obesity in
      adulthood, a simple measure of excess adiposity in adolescents is important.
      Fast, inexpensive, bioelectric impedance analysers (BIA) which rely on two foot
      pad electrodes are now available to measure % total body fat (TBF), but are less
      well investigated than conventional tetrapolar models which require the subject
      to lie prone with four electrodes attached to hands and feet. The aim of this
      study was to compare the estimation of % TBF by a foot pad analyser and a
      tetrapolar model. Male students, n = 35, 17-19 years had height, weight, waist
      and hip circumferences measured and completed a questionnaire regarding age,
      ethnicity and time of last eating and drinking. Percent TBF was measured by a
      Tanita stand-on analyser (Tanita 105, Tanita Corporation, Japan) and a SEAC
      tetrapolar model (SEAC, SFB3, QUT, Australia). Mean age (+/- SD) of subjects =
      18.2 +/- 0.6 years, BMI = 24.4 +/- 3.5 kg/m2, WHR = 0.81 +/- 0.04, % TBF, Tanita
      = 18.2 +/- 6.2 and SEAC = 20.4+/-4.8. Both measures of fat were correlated (r =
      0.84, p<0.0001). A plot of the average versus the difference of the two analysers
      found the majority of differences were above zero, especially for measures of fat
      below 22%, indicating a negative bias for the Tanita. The limits of agreement are
      between -5.4 and 9% TBF. Information provided by this study will guide gymnasium
      operators and health professionals to comment on a relative degree of adiposity
      with greater confidence of data reliability.

PMID- 14723396
TI  - Using skinfold calipers while teaching body fatness-related concepts: cognitive
      and affective outcomes.
AB  - Body composition testing has been advocated as part of fitness test batteries in
      an educational effort to promote health-related fitness, and to prevent public
      health problems like obesity. However, the measurement of the body composition of
      children and youth, especially involving the use of skinfold calipers, has raised
      concerns. In two experiments the cognitive and affective consequences of skinfold
      caliper use in a 7th grade (155 boys, 177 girls, total N = 332) health/physical
      education context were examined. Experiment 1 demonstrated that the students
      could be taught to accurately measure a partner and/or significantly learn body
      fatness-related concepts compared to controls. It was also shown that inexpensive
      plastic Fat Control calipers produced accurate measurements. Experiment 2 was
      designed to replicate the significant cognitive outcome effects, and also to test
      the hypothesis that psychological damage is a likely consequence of skinfold
      caliper use-and that hypothesis was refuted. Specifically, knowledge scores, and
      outcome scores on adapted affect scales (e.g., PANAS, MAACL), physical self
      esteem scales (CY-PSPP) and on the Social Physique Anxiety Scale supported the
      premise that skinfold calipers can be used in an educational context to
      facilitate cognitive learning without causing adverse affective consequences.

PMID- 14723397
TI  - Validity and reliability of a physical activity recall instrument among
      overweight and non-overweight men and women.
AB  - This study examined the validity and reliability of survey items measuring one
      week recall of physical activity (PA) and examined differences by weight status.
      A sub-aim of the study was to objectively assess the intensity of activity that
      most closely matches self-report. A questionnaire was administered to adults
      twice, three days apart. It was again administered after subjects wore a MTI/CSA
      accelerometer for seven days (n = 118). Several metabolic equivalent (MET)
      thresholds were applied to the accelerometer data. Agreement between test and re
      test estimates of sufficient physical activity for health benefits (150 min/week)
      was high (% agreement > 90%). Correlations (rho) between total reported PA
      (mins/day) and accelerometer data were 0.29 (p < 0.05) among men and 0.25 (p <
      0.05) among women. Among men, self-reported duration of moderate PA (3-5.9 METS)
      and accelerometer data were significantly correlated (rho = 0.40, p < 0.01), with
      no differences by weight status. Among women, a significant relationship was
      found only for those who were not overweight (rho = 0.52, p < 0.001). A
      significant correlation between self-reported duration of vigorous PA (6+ METS)
      and accelerometer data was only found for overweight men (rho = 0.40, p < 0.05).
      When lower MET thresholds were applied to the accelerometer data, women's
      reported duration of moderate-intensity PA was most strongly correlated with
      moderate PA (accelerometer) defined as 2.0-5.9 METS (rho = 0.39, p < 0.01). The
      recall instrument provides a consistent measure of physical activity and
      validation coefficients were similar to those obtained for other physical
      activity recall questionnaires. However, the ability to measure PA by self-report
      may vary by weight status.

PMID- 14723398
TI  - Is there a clinical standing balance measurement appropriate for use in sports
      medicine? A review of the literature.
AB  - The aims of this review paper are (1) to discuss the relevance of proprioception
      and standing balance in rehabilitation and prevention of sports injuries, (2) to
      examine the evidence supporting decreased balance as a risk factor and balance
      training as a prevention strategy for injury in sport, (3) to review the evidence
      in the literature supporting the reliability and validity of clinical balance
      measurements, (4) to examine factors potentially influencing lower extremity
      balance and (5) to discuss the implications for future research in identifying
      clinical balance measurement tools appropriate for use in rehabilitation and
      injury prevention in sports medicine. Laboratory measurement techniques for
      balance (using costly, highly technical, and often non-portable equipment) are
      often not appropriate for use in a clinical setting or for research in a large
      field based clinical trial. Many of the clinical tools for balance measurement
      are not appropriate for use in the healthy active population, as they are not
      challenging enough or they are static balance measures. Evidence from original
      research suggests that static unipedal timed balance is a reliable measurement in
      both children and adults. There is little evidence to support the reliability and
      validity of dynamic clinical measurements of balance developed. It is impaired
      dynamic unipedal balance in sport which may be a significant risk factor for re
      injury following rehabilitation or injury in sport. Dynamic standing balance
      measurement tools appropriate for use in the clinical setting need to be
      developed and assessed for reliability and validity.

PMID- 14723399
TI  - A pilot study of the attitudes of Australian Rules footballers towards protective
      headgear.
AB  - Despite a relatively high risk of injury to participants of Australian Rules
      football, very few players report wearing protective equipment. The aim of this
      paper is to describe the results of a pilot survey of the attitudes of community
      level Australian Rules football players towards protective headgear and the risk
      of head injury. Seventy players from four purposefully chosen clubs in
      metropolitan Melbourne completed a self-report questionnaire at the end of the
      2000-playing season. Almost all players (91.4%) reported they did not wear
      protective headgear during the 2000 season. Non-headgear users said that headgear
      was too uncomfortable (47.4%) and they didn't like it (42.1%). However, 80.0% of
      non-users said they would wear it if it prevented injury. The major motivation
      for wearing headgear was to prevent injury. Players considered rugby, boxing and
      driving a car, to be associated with a higher-risk of head injury than Australian
      Rules football. As a group, the players perceived the risk of head injury in
      Australian Rules football to be low to moderate when compared to other sports and
      activities. This partially explains why so few players wore protective headgear.
      Repeat surveys on a larger sample should be conducted to further understand the
      attitudes towards protective headgear and perceptions of risk in community-level
      Australian football players.

PMID- 14723400
TI  - Lower trunk muscle activity during the tennis serve.
AB  - Prior electromyographic (EMG) analyses of the tennis serve have focused on the
      muscles in the hitting arm and shoulder region. This preliminary study aimed to
      examine the muscle activation patterns of selected lower trunk muscles during
      three different types of tennis serve--flat, topspin, and slice. Five male highly
      skilled tennis players completed 10 trials for each type of serve. Surface EMG
      electrodes were used to monitor the rectus abdominis (RA), external oblique (EO),
      internal oblique (IO), and lumbar erector spinae (ES) muscles. For each subject,
      the two trials with the highest self-reported ratings were analysed. Average EMG
      levels during each phase of a tennis serve for each muscle were analysed using a
      non-parametric ANOVA design. No major differences in muscle activation pattern
      were found across different serve types, and bilateral differences in muscle
      activation were more pronounced in RA and EO than in IO and ES muscles. The
      abdominal muscles were more active in the topspin than in the other two types of
      serves during the upward swing of the racket. An appreciable amount of
      abdominal/low back and bilateral co-activation was observed during certain phases
      of the serve. The co-activation of lower trunk muscles may help to stabilise the
      lumbar spine during the arch back and forward swing phases of the serve. The
      results reinforce the importance of abdominal and low back exercises in the
      strength and rehabilitation programs designed for tennis players.

PMID- 14723401
TI  - Developing return-to-play guidelines following mild traumatic brain injury.

PMID- 14723402
TI  - Cricket Australia 2003 injury report.

PMID- 14723403
TI  - Physical performance standards in the ADF.

PMID- 14723404
TI  - Predictors of non-attendance from BreastScreen NSW in women who report current
      mammography screening.
AB  - OBJECTIVE: To identify among self-reported current screeners: (1) predictors of
      never attendance at BreastScreen NSW (BSNSW); (2) predictors of late or lapsed
      attendance to BSNSW (attendance to alternative providers). METHODS: Random
      samples of women aged 50-69 years were selected from the BSNSW database and NSW
      electoral roll as: current attenders to BSNSW (<27 months since last screen);
      late or lapsed attenders to BSNSW (>27 months since last screen); or women who
      had never attended BSNSW. The response rate was 71% (3,104) for a telephone
      interview that asked questions concerning demographics, medical status and health
      service usage, and opinions and behaviours related to mammography. RESULTS: Never
      attendance at BSNSW was predicted by higher income, advice from a doctor or nurse
      to have their last mammogram, recent clinical breast examination and belief that
      a referral letter is necessary. Late or lapsed attendance to BSNSW (and
      attendance to alternate providers) was associated with higher education, health
      insurance coverage, recent clinical breast examination and a family history of
      breast cancer. CONCLUSIONS: Currently screened women who do not attend BSNSW, or
      who are late or lapsed for a mammogram, appear to be influenced by referral
      patterns of their health care providers and their higher socio-economic status.
      IMPLICATIONS: BSNSW should be promoted to eligible women and general
      practitioners as a specialty mammography screening service that does not require
      a referral.

PMID- 14723405
TI  - Ovarian cancer in Western Australia (1982-98): incidence, mortality and survival.
AB  - OBJECTIVES: To investigate the trends in incidence and mortality and estimate
      survival for women diagnosed with ovarian cancer in Western Australia. CASE
      SELECTION AND METHODS: There were 1,336 women diagnosed with ovarian cancer in
      1982-98. Age-standardised rates were calculated by the direct method. Age-period
      and age-cohort models were analysed by Poisson regression. The Kaplan-Meier
      method was used to estimate survival and Cox proportional hazards regression
      evaluated the relative risk of dying. RESULTS: Trends in age-adjusted incidence
      and mortality rates showed little changed over the three time periods of
      diagnosis. A significant birth cohort effect showed a peak in the risk in the
      1924 (mid-year) cohort followed by a general decrease in both incidence and
      mortality risk. Survival at five years was 34% (95% CI 31.3-36.5) overall, but
      was only 27% (95% CI 17.4-36.7) among women with stage III and IV disease.
      Aboriginal women showed a risk of dying twice that of non-Aboriginal women.
      CONCLUSIONS: The birth cohort analysis of ovarian cancer proved better at
      explaining disease trends than was time period of diagnosis. Survival continues
      to be poor, but Aboriginal women and those with serous and unspecified
      adenocarcinoma tumours fair much worse. IMPLICATIONS: As the leading cause of
      death from a gynaecological malignancy, ovarian cancer is of public health
      importance. Historical trends in birth rates and the use of oral contraceptives
      help to explain at least some of the observed birth cohort trends in this study.
      In the long term, an effective diagnostic technique needs to be developed or this
      disease will continue to be diagnosed at an advanced stage when treatment options
      for cure are limited.

PMID- 14723407
TI  - Blood-borne viruses and their survival in the environment: is public concern
      about community needlestick exposures justified?
AB  - BACKGROUND: More than 30 million needle syringes are distributed per year in
      Australia as a component of harm-reduction strategies for injecting drug users
      (IDU). Discarded needle syringes create considerable anxiety within the
      community, but the extent of needlestick injuries and level of blood-borne virus
      transmission risk is unclear. We have undertaken a review of studies of blood
      borne virus survival as the basis for advice and management of community
      needlestick injuries. METHODS: A Medline review of published articles on blood
      borne virus survival and outcome from community injuries. RESULTS: Hepatitis B
      virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) can
      all survive outside the human body for several weeks, with virus survival
      influenced by virus titer, volume of blood, ambient temperature, exposure to
      sunlight and humidity. HBV has the highest virus titers in untreated individuals
      and is viable for the most prolonged periods in needle syringes stored at room
      temperature. However, prevalence of HBV and HIV are only 1-2% within the
      Australian IDU population. In contrast, prevalence of HCV is 50-60% among
      Australian IDUs and virus survival in needle syringes has been documented for
      prolonged periods. There have been no published cases of blood-borne virus
      transmission following community needlestick injury in Australia. CONCLUSION: The
      risk of blood-borne virus transmission from syringes discarded in community
      settings appears to be very low. Despite this, procedures to systematically
      follow up individuals following significant needlestick exposures sustained in
      the community setting should be developed.

PMID- 14723406
TI  - Time trends in lung cancer incidence by histology in South Australia: likely
      causes and public health implications.
AB  - OBJECTIVES: In response to reported increases in ratios of adenocarcinomas to
      squamous cell carcinomas of the lung in other populations, to investigate and
      consider public health and clinical implications of time trends in lung cancer
      incidence by histological type in South Australia. METHODS: 11,898 lung cancers,
      diagnosed during 1982-2000, were analysed to determine age-adjusted incidence
      rates by sex, diagnostic epoch, and histological type, and changes in
      histological distribution at diagnosis. RESULTS: The age-adjusted incidence of
      squamous cell carcinoma reduced by 47.1% in males between 1982-86 and 1997-2000,
      with larger reductions applying to younger age groups. A 34.1% reduction also
      occurred for small cell lesions in males, whereas a 55.6% incidence increase
      applied for large cell lesions, and in the age range of 70 years and over, a
      29.9% incidence increase for adenocarcinomas. Larger increases were observed for
      adenocarcinomas and large cell lesions in females. There was also a 48.0%
      incidence increase in squamous cell carcinomas in females aged 70 years or more.
      In general, adverse incidence trends were less pronounced and favourable trends
      more pronounced in the younger age groups of both sexes. CONCLUSIONS: The more
      favourable incidence trends by histology in younger age groups are a positive
      sign that hopefully will prove to be cohort effects that extend to older ages.
      Incidence trends have led to an increased proportion among diagnosed cancers of
      adenocarcinomas and large cell lesions, but this is unlikely to have more than a
      marginal effect on overall survivals and treatment requirements.

PMID- 14723408
TI  - Late HIV presentation among AIDS cases in Australia, 1992-2001.
AB  - OBJECTIVE: To describe time trends and demographic, exposure and clinical factors
      associated with late HIV presentation among notified AIDS cases diagnosed in
      Australia in 1992-2001. METHODS: AIDS cases, diagnosed in Australia and notified
      to the National AIDS Registry, were included in the analysis. AIDS cases newly
      diagnosed with HIV infection within three months of AIDS diagnosis were defined
      as cases of late HIV presentation. RESULTS: The percentage of AIDS cases with
      late HIV presentation increased significantly from 18% in 1992-96 to 33.1% in
      1997 (adjusted odds ratio (AOR)=1.79, p<0.005) and to 49.6% in 2001 (AOR=3.01,
      p<0.005). Older age, having been born in Asia, a HIV exposure history of
      heterosexual contact or an 'other/undetermined' exposure and a diagnosis of PCP
      only or of multiple AIDS illnesses, were associated with late HIV presentation
      among AIDS cases diagnosed in 1992-96 and in 1997-2001, and among overseas-born
      cases diagnosed in 1992-2001. In 1997-2001, a low CD4+ cell count was also
      associated with late HIV presentation. Among homosexually active men diagnosed
      with AIDS in 1997-2001, older age, a diagnosis of PCP or multiple AIDS illnesses
      and a low CD4+ cell count were associated with late HIV presentation. CONCLUSION:
      Predictors of late HIV presentation have remained substantially unchanged over
      time and among population subgroups, suggesting a need for innovation in HIV/AIDS
      testing and counselling strategies.

PMID- 14723409
TI  - Review of antenatal testing policies and practice for HIV and hepatitis C
      infection.
AB  - OBJECTIVE: To investigate antenatal HIV and HCV testing policy and practice in
      Australia. METHODS: A survey of private obstetricians and general practitioners
      (GPs) affiliated with the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists and directors of obstetric units in public
      hospitals was undertaken. Surveys were mailed to 40% and 20% random samples of
      private obstetricians and GPs, respectively, and all public hospital obstetric
      units. The questionnaires included information on type of antenatal policy,
      proportion of women tested for HIV and HCV, and number of HIV and HCV-positive
      women receiving antenatal care. RESULTS: Of the 995 surveys distributed, 847
      (85%) were returned. Of these 847, 277 (33%) were returned from practitioners or
      hospitals no longer involved in antenatal care. The response rates from the
      remaining practitioners (n=570) included 87% from private obstetricians, 78% from
      GPs, and 71% from public hospitals. The proportion of private obstetricians, GPs
      and public hospitals with an antenatal testing policy for HIV was 62%, 42% and
      44%, and for HCV 65%, 41% and 39%, respectively. Universal offer of antenatal
      testing among private obstetricians, GPs and public hospitals was 47%, 62% and
      23% for HIV and 54%, 46% and 23% for HCV, respectively. During 1999, an estimated
      33% of pregnant women were tested for HIV and 37% for HCV. Based on reported
      numbers of women in antenatal care, prevalence rates were estimated at 0.23 per
      1,000 and 13 per 1,000, for HIV and HCV, respectively. CONCLUSIONS: Antenatal
      testing policy and practice varies widely in Australia. The lack of uniformity
      may reflect differing policies among clinical and public health bodies.

PMID- 14723410
TI  - Disturbingly low levels of contraception among women living with hepatitis C.
AB  - OBJECTIVE: To describe the prevalence of contraception among a sample of women
      with hepatitis C (HCV), compare it with contraceptive use among Australian women
      generally, and look for associations between contraception and sample
      characteristics. METHOD: Women who self-identified as living with HCV were
      recruited through a wide range of non-clinical and clinical sites in the
      Australian Capital Territory (ACT) and Victoria to complete a self-administered
      questionnaire. RESULTS: Seventy-five per cent of distributed questionnaires were
      completed and returned. Of the 462 women surveyed, 34% of those aged 18-49
      reported using contraceptives; a much lower prevalence than the 67% in the
      Australian population. Surprisingly, women who reported concerns about
      transmission to children were no more likely to use contraceptives. Not
      surprisingly, women who were lesbian or who did not have a current partner were
      even less likely to use contraceptives. Both employed women and those not on
      benefits reported significantly higher levels of contraception. Otherwise,
      contraception did not vary with a range of variables including age, education,
      injecting drug use status, self-rated health status, experience of HCV symptoms,
      time since diagnosis, ever having received HCV treatment, or venue at which the
      participants were recruited. CONCLUSIONS: The low prevalence of contraception
      among women with HCV is both disturbing and puzzling. IMPLICATIONS: These
      findings raise several important and hitherto unconsidered issues for the sexual
      and reproductive health and well-being of women with HCV. These require both
      further research and urgent attention by service providers.

PMID- 14723411
TI  - Is median age at death a useful way to monitor improvements in mortality among
      Indigenous Australians?
AB  - BACKGROUND: Trends in the median age at death (MAAD) are now being reported in
      some official government publications. Because trends in MAAD are being published
      and are being used to support discussions about policy, information is needed
      about its strengths and limitations. METHODS: We conducted a simulation study
      based on a Markov model to investigate the relationship between the MAAD and
      mortality rates. The main time horizon was five years because this is the
      interval that is relevant for the purposes of reviewing and debating policies and
      programs, but we also continued the models out to 50 years. RESULTS: The
      simulations brought to light three problems with the MAAD. First, for populations
      with different age structures but the same age-specific mortality rates, the MAAD
      can differ by more than 20 years. Second, for Indigenous Australians, a two-year
      increase in the MAAD after five years represents a 30% decrease in the mortality
      rates, but the same increase in the MAAD for non-Indigenous Australians would
      mean only a 15% decrease in mortality. Third, large sample sizes are needed to
      show that trends in the MAAD are statistically significant. CONCLUSIONS: In the
      absence of better information, trends in the MAAD for Indigenous Australians may
      provide a way of assessing whether mortality rates are decreasing, but large
      sample sizes are needed to distinguish real change from statistical noise.
      Comparisons of trends in the MAAD between Indigenous and non-Indigenous
      Australians are even more difficult to interpret. Resources should be directed
      towards improving the validity of rates, for example, through linkage of routine
      data or investing in additional data collection.

PMID- 14723412
TI  - Improving access to cardiac rehabilitation for remote Indigenous clients.
AB  - OBJECTIVE: To identify barriers to Indigenous patients taking up a rural general
      practice-based cardiac rehabilitation program. We investigated the accessibility
      and appropriateness of the program and the role of Indigenous health workers
      (IHWs) in caring for Indigenous cardiac patients. METHODS: A cross-sectional
      survey of knowledge and views relating to cardiac rehabilitation was undertaken
      with 47 Indigenous cardiac patients and 41 health professionals in remote
      Queensland. RESULTS: Only three patients were fully engaged in the program.
      Reasons for non-participation included: lack of knowledge about rehabilitation,
      low income, and having a large extended family. Although the program incorporated
      a training component for IHWs covering prevention and follow-up, most did not
      monitor patients specifically for their heart problems and thought they did not
      have adequate skills. Shared care was occurring in some settings but without the
      participation of IHWs. CONCLUSIONS: There was general agreement that IHWs do have
      a role in cardiac rehabilitation. There is a need for ongoing in-service
      education or inclusion in training programs. Lack of understanding of the role of
      IHWs is a barrier to shared care. Cardiovascular disease needs to be addressed as
      part of the raft of chronic illnesses. IMPLICATIONS: Training about chronic
      illnesses and their management needs to be linked to structural adaptations in
      the delivery of health services to allow efficient use of each professional's
      skills. Clear role delineation needs to be negotiated to allow all health
      professionals to carry out their job effectively.

PMID- 14723413
TI  - Aboriginal and Torres Strait Islander health research and the conduct of
      longitudinal studies: issues for debate.
AB  - The National Health and Medical Research Council, Research Agenda Working Group
      (RAWG), and the literature on Indigenous health have identified the need to fill
      gaps in descriptive data on Aboriginal and Torres Strait Islander health and
      noted both the lack of research with urban populations and the need for
      longitudinal studies. This paper presents some of the broad ethical and
      methodological challenges associated with longitudinal research in Indigenous
      health and focuses particularly on national studies and studies in urban areas.
      Our goal is to advance debate in the public health arena about the application of
      ethical guidelines and the conduct of longitudinal studies in Aboriginal and
      Torres Strait Islander communities. We encourage others to offer their
      experiences in this field.

PMID- 14723414
TI  - Analysing health care systems performance: the story behind the statistics.
AB  - This commentary paper argues that the Asia-Pacific region would benefit from a
      home-grown version of the European Observatory on Health Care Systems to inform
      health sector policy: an Asia-Pacific Observatory. The countries in this diverse
      region, ranging from highly developed to very poor countries, are undergoing
      dramatic and diverse health sector changes, often on the basis of little evidence
      and with little information on successes and failures in neighbouring countries.
      The international community also is interested in knowing more about the many
      distinctive models of Asia-Pacific health care. While statistical comparisons are
      important, health policymakers and researchers need to understand the story
      behind the statistics in order to interpret the numbers and to formulate policies
      and strategies. Health system profiles therefore are useful instruments that
      describe how a complex health sector works, offer a comparative framework for
      cross-national comparisons, identify trends in health system design, and with
      standardised measures and regular updates measure progress against benchmarks.
      These reports and expanded analyses have influenced both national and Europe-wide
      debates on health policy. In the Asia-Pacific region, health systems research has
      built up a critical mass of studies and people with strong links across
      countries. The next ambitious steps are to identify sponsors able to support an
      enterprise that transcends national boundaries and to begin a project of
      comparative studies of national health systems.

PMID- 14723415
TI  - Comparison of health estimates between Victorian Population Health Surveys and
      National Health Surveys.
AB  - OBJECTIVE: The computer-assisted telephone interviewing (CATI) method has grown
      rapidly in recent years as an epidemiological tool for obtaining data on health
      issues. However, it is still argued that coverage, methods and lower response
      rates from CATI surveys compared with face-to-face interviewing may have an
      impact on the validity of the health estimates obtained. This paper compares
      demographic and health estimates from the Victorian Population Health Survey
      (VPHS) 2001, using CATI, with the National Health Survey (NHS) 2001 that is based
      on face-to-face interviews. METHODS: The profiles of the VPHS (2001) and NHS
      (2001) respondents were compared, specifically demographic characteristics (age,
      gender, marital status, country of birth, and employment status) and health
      related estimates such as self-reported health status, prevalence of diabetes and
      asthma, smoking status, daily intake of fruit, categories of psychological
      distress and private health insurance status. RESULTS: In both surveys, the
      demographic characteristics and health-related estimates of the adult population
      were remarkably similar as shown by the similarity of weighted estimates and
      overlapping confidence intervals. CONCLUSIONS: The degree to which derived
      estimates correspond in the two independent surveys lends support to the
      reliability of the CATI method used for collection of routine population health
      related data.

PMID- 14723416
TI  - Accuracy of the Australian National Death Index: comparison with adjudicated
      fatal outcomes among Australian participants in the Long-term Intervention with
      Pravastatin in Ischaemic Disease (LIPID) study.
AB  - OBJECTIVE: To assess the accuracy of the Australian National Death Index (NDI) in
      identifying deaths and recording cardiovascular and cancer causes of death.
      METHODS: Adjudicated mortality data from Australian participants in the Long-term
      Intervention with Pravastatin in Ischaemic Disease (LIPID) study up until
      September 1999 were used as reference. Nine hundred and eighty deceased subjects
      and 4,841 surviving subjects were matched to the NDI by name, date of birth, date
      of death and postcode. Matching rigour was confirmed by manual review. Deaths
      ascribed to cardiovascular and cancer causes within the NDI were also compared
      against LIPID-adjudicated causes. RESULTS: The NDI displayed 93.7% sensitivity
      and 100% specificity for the identification of deaths. Mis-recording of
      identifiers was responsible for 69% of known deaths not matching to the NDI and,
      if eliminated, would have increased the sensitivity to 98.0%. Among deceased
      subjects who matched to the NDI, cause of death was recorded in 96.2%. The
      sensitivity and specificity for cardiovascular deaths were 92.5% and 89.6%,
      respectively, and for cancer deaths 95.2% and 99.2%, respectively. CONCLUSION:
      Much of the inaccuracy of the NDI could potentially be overcome by the use of
      unique identifiers. Among deaths identified by the NDI, those due to
      cardiovascular disease are more likely to be inaccurately recorded than cancer
      related deaths, probably because less uncertainty surrounds the presence or
      absence of terminal malignant disease.

PMID- 14723417
TI  - Globalisation: public health threats--and opportunities?

PMID- 14723418
TI  - Is exposure to secondhand tobacco smoke in the home related to daily smoking
      among youth?

PMID- 14723419
TI  - Periodic motor vehicle inspections are not the answer.

PMID- 14723420
TI  - Combining reliability coefficients: possible application to meta-analysis and
      reliability generalization.
AB  - Formulae for combining reliability coefficients from any number of samples are
      provided. These formulae produce the exact reliability one would compute if one
      had the raw data from the samples. Needed are the sample means, standard
      deviations, sample sizes, and reliability coefficients. The formulae work for
      coefficient alpha, KR-20, retest, alternate-forms, split-half, interrater
      (intraclass), Gilmer-Feldt, Angoff-Feldt, validity, and other coefficients. They
      may be particularly useful for meta-analytic and reliability generalization
      studies.

PMID- 14723421
TI  - The temporal distribution of black suicides.
AB  - Suicides by both white and black groups in 1998-2002 peaked on Mondays but the
      peak was less pronounced for black suicides than for white suicides.

PMID- 14723422
TI  - Mutual exclusivity and taxonomic bias in combination lead preschoolers' word
      learning.
AB  - This study investigated preschoolers' use of two word-learning tendencies in
      combination. 22 Japanese preschoolers were tested on a task with three forced
      choices that demanded use of mutual exclusivity and taxonomic bias in the single
      trials. When presented an object whose label they had learned, an object from the
      same category as the learned object, and an object from another category, the
      children chose the third object, suggesting that they use the two constraints in
      combination. This tendency is discussed with respect to its specific application
      to word learning.

PMID- 14723423
TI  - Appeal of love themes in popular music.
AB  - The relationship between romantic satisfaction versus discontent and a preference
      for music celebrating versus lamenting love is explored. The
      satisfaction/discontent was ascertained in 60 college undergraduate women and men
      who later freely listened to music from a sampling of selections. The duration of
      their self-determined exposure to love-celebrating versus love-lamenting music
      was unobtrusively recorded by computer software. Romantically satisfied women and
      men showed a preference for love-celebrating music, whereas discontented women
      and men preferred love-lamenting music. Romantically discontent women and men
      preferred love-lamenting music presented by performers of their own sex. The
      findings indicate young adults' inclination to match emotions expressed in music
      about love with the emotions experienced in their own romantic situation.

PMID- 14723424
TI  - Roles of perceived control and coping strategies on depressive and anxiety
      symptoms of Turkish adolescents.
AB  - This study aimed to test the importance of the match between control appraisals
      and coping responses as relating to the psychological symptoms of anxiety and
      depression in adolescents. Besides this match, by means of a survey study the
      main effects of control appraisals and coping strategies were tested via
      hierarchical regression analyses, which were run for anxiety and depression
      symptoms separately. Participants were 396 students (204 girls, 192 boys) whose
      ages were 11 to 18 years. After controlling for potential factors such as
      appraisals concerning the problem features, some subject variables, and perceived
      general stress, results indicated an important discriminative feature among these
      symptoms, addressing greater use of problem-focused coping than emotion-focused
      coping, was associated with alleviated depression symptoms of adolescents. On the
      other hand, the preferring coping strategies were not related to anxiety
      symptoms. Importance of problem appraisals and coping responses in alleviating
      depression and anxiety symptoms were discussed together with their potential
      function in discriminating associates of these symptoms.

PMID- 14723425
TI  - Attitudes toward preventing versus assisting suicide: a correction to an earlier
      publication.
AB  - A sample of 50 college students was more in favor of preventing suicide than
      assisting suicide. Support for assisting suicide was associated with judging
      perceiving scores on the Keirsey-Bates Temperament Survey.

PMID- 14723426
TI  - Contributions to the history of psychology: CXIX. The Spanish Neurohistological
      School's legacy: Cajal and Lorente de No.
AB  - Santiago Ramon y Cajal made his mark in the history of science as a brilliant
      researcher of the histology of the nervous system. His bold efforts and the
      international recognition he received during his lifetime played an important
      role in the consolidation of the Spanish Neurohistological School which is
      composed of a large number of eminent disciples. Amongst these, and of
      outstanding repute, is Rafael Lorente de No whose research had a significant
      influence on the work of Canadian psychololgist Donald O. Hebb and, consequently,
      on the development of neurophysiological theory. This paper analyses some of the
      contributions of Cajal and his disciple Lorente de No which formed the anatomical
      and neuropsychological framework of contemporary psychology.

PMID- 14723427
TI  - Competitiveness and economic growth: a test of Schumpeter's hypothesis.
AB  - A study of 36 nations indicated that measures of economic growth for the period
      1980-1995 were not predicted by scores of national samples in the mid-1980s on a
      measure of competitiveness.

PMID- 14723428
TI  - Role conflict of South African women in dual-career families.
AB  - 162 female managers in dual-career families were surveyed about their perceived
      role conflict and support at home. While the majority expressed satisfaction with
      their careers, a significant proportion (72%) confirmed experiencing role
      conflict that impeded career development. Lack of husband's or partner's
      involvement in household chores was associated with role conflict. Involvement of
      the spouse or partner in household chores was also a significant correlate of the
      career aspirations of women in dual-career families. These female managers
      confirmed that, in spite of a current job meeting their career aspirations, role
      conflict was a major impediment to development.

PMID- 14723429
TI  - Childhood trauma as a possible antecedent of transliminality.
AB  - Previous theoretical and empirical work leads to a prediction that the
      developmental sequelae of childhood trauma may be risk factors in the development
      of transliminality. 106 undergraduate students completed the Revised
      Transliminality Scale and the Survey of Traumatic Childhood Events. In support of
      the prediction, scores on the Revised Transliminality Scale correlated .39
      (p<.001) with the total scores on the index of childhood trauma. Follow-up
      analyses suggested that various sorts of childhood trauma could be interpreted
      for this group as related to transliminality: having one's house destroyed,
      robbed, or vandalized; being struck by someone within or outside the family;
      being yelled and screamed at by a caregiver; witnessing the physical abuse of a
      parent; and sexual abuse. Longitudinal study is required to sharpen evidence.

PMID- 14723430
TI  - Death anxiety, death depression, and death obsession.
AB  - In a sample of 67 students, scores from Templer's and the Collett-Lester death
      anxiety scales, Templer, et al.'s death depression scale, and Abdel-Khalek's
      death obsession scale were only moderately associated, suggesting that the scales
      are measuring somewhat different constructs.

PMID- 14723431
TI  - Validation of multigenerational interconnectedness scale among Arab adolescents.
AB  - This study intends to validate the Multigenerational Interconnectedness Scale
      among Arab adolescents. The Arabic version of the scale was administered to 224
      male and 294 female Arab students in Grades 10 and 12. Principal factor analysis
      with a priori three factors and varimax rotation was conducted. This showed good
      convergence of the items into three subscales: Emotional, Financial, and
      Functional. Coefficient alpha was .80, indicating good internal consistency.
      Adolescent girls scored significantly higher on Connectedness to their families
      than the boys. Given the restricted age range, the effect of age was not
      significant. Further validation studies are needed with an external criterion for
      construct validity and a larger sample to cover the older age range of
      adolescence.

PMID- 14723432
TI  - Marijuana use and tridimensional personality traits among college students: a
      response to Hale, Whiteman, Muehl, and Faynberg.
AB  - Two important issues relevant to Hale, et al.'s 2003 study of temperament and
      self-reported marijuana use among college students are discussed. First, given
      the substantial heterogeneity within marijuana-using subject populations, it is
      key that studies of marijuana users' temperamental traits fully characterize such
      use across dimensions such as age of onset, quantity and frequency of lifetime,
      annual, and current use, and related social and health problems. Second,
      investigations should carefully address issues relating to the temporal ordering
      of marijuana use and temperamental traits such as novelty seeking and task
      persistence. Hale, et al., for example, were unable to determine whether self
      reported marijuana use contributed to low scores on Persistence (as assessed by
      the Tridimensional Personality Questionnaire) or was a consequence of low
      Persistence, or both. Longitudinal studies of diverse populations of marijuana
      users who are carefully characterized with regard to substance use, comorbid
      psychiatric conditions, and temperamental traits will substantially increase
      understanding of the role of temperament and personality in the etiology of
      marijuana abuse and dependence.

PMID- 14723433
TI  - Assessment of pathological gamblers who use slot machines.
AB  - The aim of the present study was to classify pathological gamblers based on their
      psychopathology as related to the variable sensation-seeking, and to check
      possible differences between the groups on the sociodemographic variables. The
      sample was composed of 110 male pathological gamblers using slot machines who
      requested treatment at the Pathological Gambling Unit at the Ciutat Sanitaria i
      Universitaria de Bellvitge. It was observed that pathological gamblers comprise
      three clusters, differentiated with differing severity depression, psychoticism,
      somatization, impulsiveness, interpersonal sensitivity, and phobic anxiety.
      Cluster 1, representing 46.7% of the sample, showed mean scores higher than or
      equal to T=63. On the subscales of Depression, Psychoticism, Interpersonal
      Sensitivity, Phobic Anxiety, and Obsessiveness-Compulsiveness the score was close
      to T=63 (the clinical cut-off score). Cluster 2, representing 23.8% of the
      sample, scored higher than Cluster 1 on the following subscales: Depression,
      Phobic Anxiety, Interpersonal Sensitivity, Psychoticism, Obsessive-Compulsive,
      and Somatization. On Cluster 3 highest mean scores were observed on all SCL-90-R
      dimensions relative to the other two groups. What distinguished these subgroups
      is not symptomatology but the severity of the psychopathology. On the other hand,
      sensation seeking was similar for the three clusters, and the slight differences
      depended on the subjects' psychopathology.

PMID- 14723434
TI  - Addendum to P. L. Baldi (1998).
AB  - The aim of this follow-up study was to evaluate the persistence of the
      memorization strategies of 65 mentally retarded adolescents (M IQ of 53). Mean
      correct recall was best for drawings for which semantic elaboration was suitable
      for both immediate and 1-hr. recall.

PMID- 14723435
TI  - Associations of family support, resiliency, and depression symptoms among
      indigent teens attending a family planning clinic.
AB  - The goal of this study was to examine the effect of resiliency and family support
      on depression symptoms among 110 indigent adolescents attending a family planning
      clinic in a large urban city in southwestern USA. Findings suggested that several
      of the resiliency domains, on the Individual Protective Factors Index, as well as
      family support measured by the Family Support Scale, were associated with
      depression symptoms. Scores on the self-concept and positive outlook dimensions
      of the Personal Competence domain, the confidence and assertiveness dimensions of
      the Social Competence domain, and family support correlated with depression
      symptoms. The findings also suggested that 16.4% of the teens in this clinic
      would be classified as clinically depressed and as needing further evaluation. It
      seems reasonable to conclude that resilient adolescents may possess
      characteristics, beliefs, and supports which enable them to cope with life
      stressors more effectively and avoid depressive symptoms than those who are not
      as resilient. Given the prevalence and extent of depression among adolescents, it
      is important to develop interventions to foster attachment and enhance individual
      protective factors in primary prevention programs as such interventions may
      ameliorate the effects of high-risk environments.

PMID- 14723436
TI  - Seatbelt use and belief in destiny in a sample of South African Black and White
      drivers.
AB  - The aim of the study was to investigate the association between fatalism and
      seatbelt use. The sample included 100 Black and 100 White drivers recruited from
      shopping complexes and petrol stations in an urban area in the Northern Province
      of South Africa. Seatbelt use of drivers was recorded unobtrusively, and self
      reported seatbelt use and belief in destiny (fatalism) were subsequently obtained
      by interview. A total of 44% Black and 50% White drivers (47% men and 47% women)
      were observed wearing their seatbelts. The majority of the drivers (84% of Blacks
      and 79% of Whites) did not have a fatalistic orientation. A nonfatalistic
      orientation was significantly associated with observed seatbelt use and self
      reported seatbelt use. Logistic regression analysis identified a nonfatalistic
      orientation as independent predictor for observed seatbelt use.

PMID- 14723437
TI  - Conditional covariation of binge drinking with predictors of college students'
      cheating.
AB  - Recent research has identified a variety of significant predictors of academic
      dishonesty, but virtually no studies have examined the conditional relation of
      binge drinking and students' cheating. Using a survey sample of 289 college
      students, this study tested the mediating relations of binge drinking with the
      correlation of independent variables--including opportunity, strain, and self
      control--on self-reported academic dishonesty. Low self-control had a stronger
      correlation with students' cheating behaviors for those who were heavy binge
      drinkers (beta = -.52) than for students who were nonbingers (beta = -.38).
      Differential relations were found for other key variables, namely, opportunity
      and strain, at varying severities of binge drinking.

PMID- 14723438
TI  - Advances in measurement of global risk indicators in lives of court-involved
      youth: brief evidence for concurrent validity.
AB  - The present study reports data on the concurrent validity for the Global Risk
      Assessment Device, a measure of global risk indicators for a sample of 37
      families of adolescents who participated in a family-based program designed to
      divert youth out of the justice system. Significant correlations among three
      domains of risk (family/parenting, substance use, and personality/behavior
      problems) and other measures generated preliminary evidence for concurrent
      validity of this global risk measure.

PMID- 14723439
TI  - Perceptions of counselor-trainees given content of a pre-intake form.
AB  - 88 counselor-trainees were given information about a potential client using
      either a problem-focused or strength-focused pre-intake form. Based on the
      information provided, counselor-trainees rated the client on the perceived
      severity of client's problem, difficulty of treatment, attractiveness of case,
      anticipated duration of treatment, and usefulness of the pre-intake information.
      This pilot project suggested that the type of information provided to trainees
      influenced their perceptions of the case, in particular, affording a more
      positive view of the client.

PMID- 14723440
TI  - Effects of seating positions on heart rates, state anxiety, and estimated
      interview duration in interview situations.
AB  - This study examined the effects of three seating positions, face-to-face, side-by
      side, at right-angles, on participants' heart rates, anxiety, and estimated
      duration of interview. The subjects were 84 students in a women's junior college
      who were divided into two groups, classmates and nonclassmates. The experiment
      used the three seating positions in each of the two groups during the interviews.
      Heart rates, anxiety scores, and estimated duration of interview were measured.
      There was a significant effect in different seating positions on the heart rates
      among the participants. The results suggest that the face-to-face seating
      produces increased arousal compared to the side-by-side and right-angled seating
      positions. However, this arousal seems to be more important among classmates than
      nonclassmates. The results and implications are discussed.

PMID- 14723441
TI  - Perceptions of the ideal mediator: an Israeli-Palestinian example.
AB  - Although research on mediation documents the ideal problem-solving strategy of
      the mediator, the steps involved in developing a successful mediating process,
      and the political and economic resources that facilitate mediation, there is
      usually no indication that the members of both sides might have different
      attitudes toward these variables and in particular toward the personality traits
      of the ideal mediator. Data that document the perceptions of Israeli Jews and
      Palestinians collected during the early phase of the intifada (uprising) in 2001
      are used as an example. Although both groups indicated that a mediator should be
      task-oriented, the Israeli Jews wanted a mediator over three times as friendly as
      the one desired by the Palestinians.

PMID- 14723442
TI  - Concurrent and divergent validity of the Spanish form of Templer's Death Anxiety
      Scale.
AB  - The aim of this study was to examine the concurrent and divergent validity of the
      Spanish form of Templer's Death Anxiety Scale. A sample of 328 Spanish students
      responded anonymously to a questionnaire which, in addition to the Death Anxiety
      Scale, included the Spanish forms of two death anxiety scales and two scales of
      general anxiety. Although the correlations with measures of death anxiety were
      notably higher than those with measures of general anxiety, there were positive
      and significant correlations between scores on the Death Anxiety Scale and on all
      the other scales, denoting the concurrent and divergent validity of the Spanish
      form of the Death Anxiety Scale.

PMID- 14723443
TI  - A cross-cultural examination of children's understanding of "the enemy".
AB  - Despite the apparent ease and regularity with which adults label individuals and
      groups as "the enemy," little is known regarding how children understand this
      concept. The current qualitative study examined the concept of enemy as
      understood by 105 3- to 12-yr.-old children from two sides of an international
      conflict--Yugoslavia and the United States. This article provides an analysis of
      the children's answers during a structured interview regarding their
      understanding of enemies, specifically the perceptions of children in a war zone
      and the perceptions of children living in relative safety. Children of all ages
      could discuss the concept of enemy. They described both interpersonal and group
      conflict. A common theme in both Yugoslavian and U.S. children's descriptions was
      that an enemy is someone who is bad or does bad things. The children recognized
      the importance of at least two "sides" and discussed reciprocal or mutual
      feelings. In general, the children showed great optimism that one's enemies can
      become one's friends. These findings are interpreted in terms of developmental
      issues and sociopolitical context.

PMID- 14723444
TI  - Emotional intelligence and perceived employability for internship curriculum.
AB  - Emotional Intelligence dimensions of motivation as well as social and
      communication skills were associated with perceived entry-level employability.
      Feedback from internship hosts was the measure of association for 77 college
      juniors or seniors between the ages of 18 and 22 (49 women, 28 men), enrolled in
      a one-semester communications internship. Chi squared supported the hypothesis
      that interns scoring high on emotional intelligence are more likely to be
      considered for employment by the internship host than those scoring low. Given
      replication of this work applications for an internship curriculum can be
      identified.

PMID- 14723445
TI  - Molestations by homosexual foster parents: newspaper accounts vs official
      records.
AB  - To assess whether a systematic tally of newspaper accounts reflect official
      foster-parent molestation a review of 6,444 news stories on Lexis-Nexis Academic
      Universe from 1989 through 2002 about child molestation yielded 33 stories
      involving foster parents. Of the 25 foster-parent perpetrators, at least 15 (60%)
      engaged in homosexuality. In Illinois 1997-2002, 92 (34%) of 270 foster- or
      adoptive-parent perpetrators who engaged in "substantiated" sexual abuse
      homosexually abused their charges. These findings suggest that the proportion of
      homosexual perpetrators in a systematic tally of newspaper stories is similar to
      the proportion of homosexual perpetrators in datasets from large entities and put
      in question the current policy of utilizing homosexuals as foster and adoptive
      parents.

PMID- 14723446
TI  - Obsession-compulsion and its relation to age and sex in Kuwaiti and American
      students.
AB  - To estimate the correlation between scores on obsession-compulsion and both age
      and sex, two studies were carried out with Kuwaiti (n1=87, n2=460), and American
      (n1=73, n2=273) undergraduates. The Arabic Obsessive-Compulsive Scale was used in
      both studies. Significant correlations were found for the Kuwaiti sample;
      however, these correlations were of low magnitude and have no practical value.

PMID- 14723447
TI  - Psychometric properties of the proactive attitude scale in students at the
      University of Hong Kong.
AB  - The 15-item Proactive Attitude Scale is defined as a unidimensional measure of
      belief in one's ability to effect positive life changes. The current study tested
      the scale's unidimensionality assumption with confirmatory factor analysis on a
      mixed sample of 157 fourth-year Bachelor of Education (n=30) and first year
      Masters of Education (n=121) students from The University of Hong Kong. 49 were
      men and 108 women, with a median age of 31 yr. The confirmatory factor analysis
      showed that a two-factor congeneric model fit the data significantly better than
      the unidimensional model. The two factors were characterized as reflecting
      proactive attitude and independent mindedness, respectively. The moderate
      correlation between these factors clearly defined them as reflecting distinct
      constructs, making untenable the scale's unidimensionality assumption.

PMID- 14723448
TI  - Prediction of readmission of psychiatric inpatients.
AB  - Using demographic and episode-based variables this study attempted to predict
      which patients would require frequent psychiatric hospitalizations. Records of
      943 patients were randomly selected from 14,649 admissions and examined for a 5
      yr. period following initial admission. Sex, ethnicity, and age at first
      admission were not significantly related to readmission. Among the demographic
      variables, marriage was inversely related to readmission. Involuntary commitment
      and a longer length of stay at the original admission were associated with a
      higher rate of readmission. Despite the results being statistically significant,
      the small covariances of these effects indicate little clinical utility in the
      prediction of readmission for an individual patient.

PMID- 14723449
TI  - Religion and personality among religious studies students: a replication.
AB  - To replicate the 1999 work of Francis and Fearn, 360 religious studies students
      between the ages of 16 and 18 years completed the abbreviated Revised Eysenck
      Personality Questionnaire and the Francis Scale of Attitude toward Christianity.
      Analysis confirmed the results of Francis and Fearn and supported the general
      finding that scores on Psychoticism (r =-.25), but neither those on Extraversion
      nor Neuroticism, were significantly associated with rated religiosity.

PMID- 14723450
TI  - Parenting styles and academic achievement in college students.
AB  - The purpose of this study was to investigate the relationship between parenting
      styles and college academic achievement. An ethnically diverse group of college
      students reported their GPA and responded to the Parenting Style Index. Parenting
      style scores were unrelated to college GPA. Additional analyses of ethnic groups
      indicated differences in maternal involvement and strictness and relationship of
      these variables to GPA.

PMID- 14723451
TI  - Phenomenological contributions to understanding hypnosis: review of the
      literature.
AB  - This article provides a summary of the available qualitative literature on
      hypnosis of importance to empirical study of hypnosis. The author advocates a
      link between phenomenological research and the qualitative research of perceptual
      theory to deepen an understanding of hypnosis previously missing in the research
      literature and in debates on the theoretical approaches to hypnosis. The author
      suggests linking Giorgi's and Wasicsko's research methodologies to advance
      qualitative research. Researchers could conduct more qualitative research on the
      experience of hypnosis to expand and explicate subjective experiencing and
      enhance exploration of individual differences that cannot be captured in
      artificially controlled environments.

PMID- 14723452
TI  - Value correlates of collegiate alcohol abuse.
AB  - This study tested whether problematic alcohol use correlates with different
      values clusters in the Schwartz Values Survey. Participants were 156 midwestern
      university students (M=21.6 yr., 63% women). We used two alcohol-use assessment
      methods, one involving behavior checklist reports with a questionnaire, the other
      a two-week daily log procedure. Although exploratory in nature, we took as most
      important those relationships between alcohol use and values which replicated
      across both measures. Those who drank frequently and problematically were most
      likely to endorse a hedonistic and stimulation-seeking values system.

PMID- 14723453
TI  - University students' approaches to learning first-year mathematics.
AB  - This study assessed reliability and validity of the Approaches to earning
      Mathematics Questionnaire, for 218 university students. The study also identified
      the relationship between subscales. Internal consistency as Cronbach alpha was
      .77 for the Surface Approach to Learning scale and .88 for the Deep Approach to
      Learning scale. Principal components analysis yielded a two-factor solution
      accounting for only 34.6% of variance. The factors were interpreted as Surface
      Approach and Deep Approach to learning mathematics, as in Australia. The former
      subscale scores were negatively correlated -.2 with the latter subscale scores.

PMID- 14723454
TI  - Work social agency as a function of self-esteem and Machiavellianism.
AB  - Using a national sample of 127 legal, accounting, and human resource
      professionals, from 1,500 solicited, this study identified two dispositions
      related to social agency at work. After controlling for several individual
      factors, the analysis indicated that work social agency was associated with
      increased self-esteem and decreased Machiavellianism.

PMID- 14723455
TI  - A mediational model of the relationship between linguistic acculturation and
      polydrug use among Hispanic adolescents.
AB  - Hispanic seventh and eighth graders (N=1,038) in 22 New York City middle or
      junior high schools completed self-report questionnaires with items related to
      drug use (cigarette smoking, alcohol use, and marijuana use), linguistic
      acculturation (language use with parents), perceived peer smoking norms,
      perceived peer drinking norms, and psychological distress. Students who spoke
      English with their parents and bilingual students who spoke English and Spanish
      with their parents engaged in greater polydrug use than those who spoke Spanish
      with their parents. Bilingual students perceived that a higher proportion of
      their peers drink than those who spoke Spanish with their parents, and this
      higher perception of their peers' drinking was associated with greater polydrug
      use controlling for linguistic acculturation. In the final model, linguistic
      acculturation was no longer significant and peer drinking norms predicted
      polydrug use, peer drinking norms mediated the relationship between linguistic
      acculturation and polydrug use, but not peer smoking norms and psychological
      distress.

PMID- 14723456
TI  - Relation between employees' religiosity and job involvement.
AB  - While it has been argued that religion influences the meaning of work, few
      studies have empirically examined how employees' religiosity and job attitudes
      relate to one another. Specifically, this study investigated the relations among
      three religious orientations (intrinsic, extrinsic-personal, and extrinsic
      social) and job involvement for 100 employees of a rehabilitation hospital in the
      southern United States. The respondents completed the 1989 Intrinsic/Extrinsic
      Revised Scale and the 6-item version of the 1965 Job Involvement Scale.
      Correlation indicated a negative association between Intrinsic Religiosity and
      Job Involvement (r=-.26, p<.05) and a positive one between Extrinsic-personal and
      Job Involvement (r=.23, p<.05) for the total sample. When separated by religious
      affiliation, regression analyses indicated a significant positive relationship
      between scores on Extrinsic-personal Religiosity and in Job Involvement for
      Protestants (B=.32, p<.01), but Intrinsic Religiosity was signifiantly negatively
      related to Job Involvement for non-Protestants (B=-.35, p<.05). No relation was
      found between scores on Extrinsic-social Religiosity and Job involvement for
      either group. These results suggest that employees' religiosity may influence
      work values in different ways for Protestant and non-Protestant workers.

PMID- 14723457
TI  - Age and sex differences in self-esteem among Spanish adolescents.
AB  - This study examined the relation of self-esteem with sex and age for 660 Spanish
      students (400 secondary school students, 260 university students, age range 12 to
      28 years), who responded to the Rosenberg Self-esteem scale. Analysis indicated
      no sex differences in general self-esteem, but there were differences with
      respect to age. Persons 12 to 16 years old had lower self-esteem than others
      between the ages of 17 and 28 years.

PMID- 14723458
TI  - Cell phones, clothing, and sex: first impressions of power using older African
      Americans as stimuli.
AB  - Sex, material possessions, and race have long been associated with prestige or
      status in American society, yet little research has examined this idea. Little is
      known about the effect of cell phones on first impressions. In a 2 (cell phone:
      present, absent) x 2 (clothing: jacket, no jacket) x 2 (sex) between-subjects
      design, 160 women from a predominantly Black college rated stimuli of older,
      African Americans on 15 items measuring perceived power on three power subscales:
      expert, legitimate, and coercive. Multivariate analysis of variance showed a 3
      way interaction for clothing, cell phone, and sex of stimulus person.

PMID- 14723459
TI  - Exploring the dimensionality of the Originality subscale of the Kirton Adaption
      Innovation Inventory.
AB  - The Kirton Adaption-Innovation Inventory, which is a widely used measure of
      innovative (as opposed to adaptive) cognitive individual style, is believed to
      have three dimensions: Sufficiency of Originality, Efficiency, and Rule/Group
      Conformity. Several studies have raised concerns regarding its construct
      validity, specifically with respect to the Sufficiency of Originality subscale.
      Within this subscale, exploratory factor analysis identified two distinct
      subdimensions, Idea Generation and Preference for Change. In this study, we used
      a sample of 356 household participants (with an average age of 56 yr., average
      income of 39,700 dollars, and average of 15 yr. of education) from the Arkansas
      Household Research Panel. We then employed Bollen and Grandjean's approach based
      on confirmatory factor analysis to assess whether there are actually two distinct
      subdimensions instead of one. Our study shows that within the Sufficiency of
      Originality subscale, there are indeed two distinct subdimensions, Idea
      Generation and Preference for Change. Further analyses indicate that dropping
      double-loaded items identified through exploratory factor analysis significantly
      improves the fit statistics. Also, allowing correlated errors for the measurement
      items that belong to the same subdimension can also significantly improve the
      overall fit of the model based on chi-square statistics.

PMID- 14723460
TI  - Are sex differences in sexual vs emotional jealousy explained better by
      differences in sexual strategies or uncertainty of paternity?
AB  - In a classic 1992 study, Buss, Larson, Westen, and Semmelroth reported that men
      were more distressed by the sexual infidelity of a partner and women were more
      distressed by a partner's emotional infidelity. Buss, et al. suggested that men
      are concerned about uncertainty of paternity, that is, the possibility of raising
      another man's child while believing that the child is his own. However, data can
      be explained in terms of men's greater preference for short-term sexual
      strategies. This research yielded support for the latter explanation for the
      samples in this present research.

PMID- 14723461
TI  - Respiration-related artifacts in EDA recordings: introducing a standardized
      method to overcome multiple interpretations.
AB  - When electrodermal activity (EDA) recordings are controlled for artifacts, i.e.,
      electrodermal reactions [EDRs] elicited by breathing irregularities, several
      problems arise. For example, respiration is difficult to evaluate because there
      are no clear-cut criteria for its values, e.g., wave form, depth. Furthermore,
      respiration and EDA are rather complexly intertwined, and there is no established
      or standardized method for evaluation. Especially when subjects are not
      stimulated, i.e., when nonspecific EDRs are taken, EDR recordings elicited by
      irregular breathing may overestimate the subject's arousal and bias any given
      research question. Moreover, incidences of concurrent consecutive EDRs and
      changes in respiratory activity may encourage multicausal interpretation due to
      both signals' having a common central causation. To circumvent such problems, we
      developed a method which provides rule-based guidelines to identify potential
      artifacts. Two experiments (N = 14 and N = 12) were conducted to test the
      accuracy of the judgments of three independent raters. The reliability
      coefficients for the number of electrodermal reactions and the sum of their
      amplitudes yielded satisfactory coefficients of convergence for each individual
      experiment (.87 and .82 in Exp. 1 vs .94 and .95 in Exp. 2) as well as for the
      two experiments combined (.92 and .91).

PMID- 14723462
TI  - Internships: most and least favored aspects among a business school sample.
AB  - This study reports the results of a content analysis involving 143 senior and
      junior year business school students enrolled in a semester-long internship
      course for credit (74 males and 69 females). Responses to the question, "What did
      you like most/least about your internship position?" are reported. Positive
      aspects of internship are discussed in relation to the Job Characteristics Model.

PMID- 14723463
TI  - Personality change of officer cadets in the Canadian Forces.
AB  - The present research assessed the extent to which 46 officer cadets'
      personalities changed as a result of spending four years in a military academic
      institution. Four personality variables were examined, Surgency, Achievement,
      Conscientiousness, and Internal Control. Given the nature of the military
      environment and training, we hypothesized that individuals' scores on these
      scales would increase with time. Analysis indicated scores on all four scales
      decreased. A confound occurred as in the first administration of the measure
      participants were completing the measure as part of a selection procedure whereas
      in the second one participants completed measures voluntarily.

PMID- 14723464
TI  - Agreement among readers on what is relevant in self-help psychology books.
AB  - It was hypothesized that text marking in self-help psychology books would
      indicate that readers agree on which pages and lines contain relevant
      information. Previously owned copies of two self-help book titles (n=48, n=38),
      all with marked text, were collected from second-hand book stores and scored for
      line and page marking. Chi-squares for goodness-of-fit yielded significant
      differences between observed and chance agreement in marking behavior. Intraclass
      and KR-20 correlations were significantly different from zero, suggesting that
      readers agreed on what information was relevant and irrelevant. Actual users of
      self-help books may have similar standards because of cultural values, social
      group relations, or common problem experiences.

PMID- 14723465
TI  - National character and Internet use.
AB  - Measures of extraversion and neuroticism for 18 industrialized nations were
      associated with Internet use.

PMID- 14723466
TI  - Lifespan-developmental differences in physiologic reactivity to loud tones in
      trauma victims: a pilot study.
AB  - Age at exposure to trauma has been identified as a risk factor for severity of
      trauma sequelae due to the developmental vulnerability of several brain
      structures involved in trauma processing. To investigate whether persons
      traumatized in adolescence show elevated arousal and startle reaction parameters,
      we studied persons traumatized by political imprisonment in the former East
      Germany either in their late adolescence or young adulthood (17-22 years, n=9) or
      middle adulthood (35-50 years, n=6). Physiological reactions (skin conductance,
      heart rate) to loud tones and self-report tests were measured. Covariance
      analysis yielded one significant difference, mean skin conductance response, with
      a higher mean for the younger group. Results are discussed in light of its
      limitations and further prospects.

PMID- 14723467
TI  - Aggressive content of high school students' TV viewing.
AB  - The purpose of this study was to examine high school students' exposure to
      television programming with aggressive content and to explore whether consumption
      of aggressive TV varied by sex and ethnicity. Participants were 472 boys and
      girls from two high schools, one urban and one suburban. Definitions of both
      direct and indirect aggression were used to rate TV programs, and the
      participants' exposure to both was assessed. Analysis yielded a statistically
      significant effect for sex but not ethnicity as girls watched more TV programs
      containing indirect aggression. Also, exposure to aggressive TV content peaked in
      Grade 10 and fell sharply thereafter. The importance of educating adolescents
      about the images they view is highlighted. Implications for research are
      discussed.

PMID- 14723468
TI  - PC versus Macintosh users: a follow-up study.
AB  - In a sample of 287 students, Macintosh users had significantly greater anxiety
      about computers than PC users.

PMID- 14723469
TI  - Variables related to graduate students' willingness to forgive a job-related
      transgression.
AB  - 43 graduate students' willingness, within a hypothetical situation, to forgive a
      friend whose negligent actions negatively affected their chances of getting a job
      was examined. Self-actualization, age, and general interpersonal closeness were
      proposed as possible variables related to these students' ratings of willingness
      to forgive while controlling for sex. A hierarchical multiple regression analysis
      showed this model predicted 23% of the variability in Forgiveness scores using
      self-actualization and age as significantly related to forgiveness in a positive
      direction, but with sex and general interpersonal closeness showing no
      significant relation.

PMID- 14723470
TI  - The moderator effect of test anxiety in the relationship between test expectancy
      and the retention of prose.
AB  - The effect of test expectancy and test anxiety on the retention of prose is not
      yet profoundly examined in an ecologically valid learning context. The influence
      of test expectancy, test anxiety, and differences in intelligence on the
      retention of prose was addressed in the hypothesis that test anxiety would act as
      a moderator between test expectancy and memory retention of prose. Also examined
      was whether this relation would still be valid if differences in general
      intelligence were controlled. University freshmen (N=292) participated. Analysis
      indicated that test anxiety acted as a moderator between test expectancy and
      prose memory performance, even after controlling for differences in general
      intelligence. The low and high test-anxious group expecting a retention test
      seemed to profit from positive arousal elicited by the expectedness of a
      retention test. The high test-anxious group not expecting a retention test
      performed in a rather detrimental way on a retention test given negative arousal
      elicited by the unexpectedness of a retention test. Implications for further
      research are elaborated and discussed.

PMID- 14723471
TI  - Three decades of psychological research in the journal Cognitive Psychology (1979
      1999).
AB  - We examined the journal Cognitive Psychology, as representative of the evolution
      of cognitive psychology during the last three decades (1979-1999). Analysis of
      changes in the impact factor defined according to the Social Science Citation
      Index (SSCI) is an indication of the ranking of this journal both in the general
      classification of archival research journals as well as in relation to other
      periodicals in the area of cognitive psychology. This single quantitative measure
      of articles published in Cognitive Psychology indicates a change in the topics of
      interest. An analysis of the research topics and identification of the most
      productive authors identifies important indicators of the psychological topics of
      primary interest during this time.

PMID- 14723472
TI  - Cognitive styles in creative leadership practices: exploring the relationship
      between level and style.
AB  - This study investigated the relationship between two measures used to assist
      change and transformation efforts, the Kirton Adaption-Innovation Inventory which
      assesses style or manner of cognition and problem-solving, not level or
      capability, and the Leadership Practices Inventory which measures the extent to
      which leaders exhibit certain leadership behaviors associated with accomplishing
      extraordinary results. These two measures of level and style should be
      conceptually distinct and show no or only modest correlation. Analysis yielded
      statistically significant and meaningful relationships between scores on the
      Kirton inventory and two scales of the Leadership Practices Inventory.
      Implications and challenges for research and practice were outlined.

PMID- 14723473
TI  - The emperor' s new clothes.

PMID- 14723474
TI  - Tramadol versus buprenorphine for the treatment of opiate withdrawal: a
      retrospective cohort control study.
AB  - Various drugs have been used for the treatment of opioid withdrawal, e.g.,
      methadone, buprenorphine, and clonidine. Tramadol is a centrally acting synthetic
      analgesic agent with opiate activity due to low affinity binding of the parent
      compound and higher affinity binding of the O-demethylated metabolite M1 to mu
      opioid receptors. As a consequence, there may be a role for the use of tramadol
      in the treatment of opiate withdrawal. We attempt to assess the efficacy of
      tramadol in treating moderate heroin withdrawal through a retrospective cohort
      control study, conducted in a detoxification unit in a community teaching
      hospital. Out of 100 heroin abusers admitted for detoxification during the review
      period, 64 patients who were treated either with buprenorphine or tramadol, were
      included in this study, with 20 participants in the buprenorphine group and 44 in
      the tramadol group. Both groups were matched for age, sex, and self-reported
      average quantity of heroin used per day. In the tramadol group, the average CINA
      maximum was 9.0, and in the buprenorphine group it was 11.2 (P = 0.07). The use
      of oral clonidine per patient in the tramadol group was 1.6 tablets, and in the
      buprenorphine group 0.1 tablets (P = 0.002). The length of stay was 3.7 days in
      the tramadol group and 4.1 days in the buprenorphine group (P = 0.5). Four
      participants in the tramadol group received three or more doses of buprenorphine
      because their symptoms were not controlled, and were considered as treatment
      failures. These preliminary data suggest that tramadol may be comparable to
      buprenorphine in the management of mild to moderately severe heroin withdrawal.
      These findings, if reproduced in larger studies with stronger research designs,
      have potentially great implications for the management of opioid withdrawal in
      both the inpatient and outpatient setting.

PMID- 14723475
TI  - The use of tramadol for acute heroin withdrawal: a comparison to clonidine.
AB  - Using a retrospective chart review, 59 patients detoxified with tramadol were
      compared to 85 patients detoxified with clonidine on rates of leaving against
      medical advice (AMA) and control of withdrawal symptoms. Patients detoxified with
      tramadol had 23% (95% CI, 0.09-0.59; P < .01) the risk of leaving AMA and scored
      an average of 0.24 points lower (95% CI, 0.08-0.41; P < .01) on a 0-3 point
      withdrawal symptom scale compared to patients detoxified with clonidine. This
      preliminary study indicates that tramadol is more effective in managing
      withdrawal than clonidine, and may be especially useful in outpatient
      detoxification.

PMID- 14723476
TI  - A peek into Pandora's box: the medical excuse marijuana controversy.
AB  - The smoking of marijuana for medicinal applications is a volatile and difficult
      issue for the medical and regulatory communities which has reached the forefront
      of discussions of public policy. Any consideration of this issue must take into
      account the substantial toxicity, impurity, and morbidity associated with
      marijuana use. Several states have passed ballot initiatives or legislation that
      allow a medical excuse for possession of marijuana. These initiatives bypass the
      Food and Drug Administration process of proving safety and efficacy, and they
      have created serious regulatory dilemmas for state regulatory boards. Several
      examinations of the issue have consistently drawn question to the validity of
      smoking an impure substance while voicing concern for the well being of patients
      in need. The historical, social, medical, and legal issues are examined.

PMID- 14723477
TI  - Circuit parties and patterns of drug use in a subset of gay men.
AB  - This study examined the characteristics of gay men attending circuit parties and
      their drug use. In particular, the role of methylenediomethamphetamine (MDMA,
      "ecstasy") was considered in relation to other drug use and sexual behavior. A
      one-page survey was distributed to 173 men attending a circuit party. Respondents
      were generally gay men, Caucasian, employed, and well-educated. Twenty-five
      percent self-identified as HIV-positive. Eighty-six percent reported using at
      least one substance on the day of the party; polydrug use was frequent. The most
      common substances were MDMA, ketamine, and methamphetamine. MDMA use was highly
      associated with ketamine, methamphetamine, and cocaine use. MDMA use was also
      associated with significantly more receptive anal intercourse. Circuit parties
      are settings of increased drug use and associated high-risk sexual behavior. A
      better understanding of these issues is needed to develop interventions aimed at
      reducing drug use and sexual risk taking among gay men who attend circuit
      parties.

PMID- 14723478
TI  - Gender similarities and differences: the prevalence and course of alcohol- and
      other substance-related disorders.
AB  - Changes in women's social role over the past years likely influenced the gender
      gap in substance use and substance-related disorders, with potentially
      significant prevention and treatment implications. The authors reviewed the
      literature about gender differences in prevalence estimates and course of
      substance-related disorders. Male-to-female ratios of prevalence estimates of
      substance use are narrowing in different countries. The initiation of substance
      use is progressively taking place at younger ages, the trend being more dramatic
      among women as compared to men. Women's accelerated progression to dependence (so
      called "telescoping effect") is a robust finding among alcohol-dependent
      individuals, although the effect seems to be weaker among younger individuals. As
      for other drugs, the literature is weaker and further research is needed. It is
      concluded that women's earlier age of initiation of substance use, faster
      progression to dependence and under-representation in addiction treatments should
      be addressed in future health care planning.

PMID- 14723479
TI  - The effect of nicotine patch therapy on depression in nonsmokers: a preliminary
      study.
AB  - Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD)
      indicate rapid reduction in depressive symptoms with nicotine patch therapy. This
      randomized, double-blind, placebo-controlled pilot study examined the effect of
      nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with
      current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6
      (5 females, 1 male) completed the study. Participants received either placebo (n
      = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic
      visits during patch therapy and a final visit on Day 12. Depressive symptoms were
      assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change
      in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1
      of patch use. Similar decreases in HRSD scores were observed for placebo and
      active patch groups. Among the placebo participants, the mean HRSD score
      decreased (p = 0.038) by Day 2. The study needs replication with a larger sample
      and utilizing novel recruitment strategies.

PMID- 14723480
TI  - Timing of alcohol and smoking cessation (TASC): smoking among substance use
      patients screened and enrolled in a clinical trial.
AB  - Tobacco dependence is prevalent among alcohol dependent patients, and causes
      increased morbidity and mortality. Concurrent treatment for these disorders may
      be advantageous, but there are concerns about adverse effects on alcohol
      treatment outcomes. The Timing of Alcohol and Smoking Cessation (TASC) Study is a
      randomized controlled clinical trial to compare the effectiveness of smoking
      cessation treatment offered concurrently or six months following intensive
      rehabilitation for alcohol dependence. This paper describes the study design and
      baseline characteristics of the study population. Participants were current
      smokers in intensive alcohol dependence treatment, with willingness to consider
      quitting smoking. Smoking intervention offered behavioral and pharmacological
      treatment. One thousand nine hundred forty-three patients were screened for
      enrollment; 499 were eligible and participated (26%). We describe demographic
      characteristics, smoking behavior and attitudes among participants and
      nonparticipants toward smoking cessation and drinking. We conclude that there is
      considerable interest in smoking cessation in alcohol dependent treatment
      populations, and recruitment to research studies is feasible.

PMID- 14723481
TI  - Guideline development for office-based pharmacotherapies for opioid dependence.
AB  - The success of opioid agonist maintenance has stimulated efforts to make this
      form of treatment more available. Methadone medical maintenance, coordination of
      methadone services from a physician's office, has been offered as an alternative
      to narcotic treatment programs for stable, recovered and socially rehabilitated
      opioid dependent patients. Despite the successful implementation of methadone
      medical maintenance programs, a number of important questions regarding the
      appropriate guidelines for the use of this model of care remain. The current
      paper reviews the process and outcome of the Medical Maintenance Consensus Panel,
      which was convened for the federal Center for Substance Abuse Treatment. We
      outline the process and describe the two guidelines that were produced by this
      process that are targeted at physicians, narcotic treatment programs, and policy
      makers.

PMID- 14723482
TI  - Comparative evaluation of measles, mumps & rubella vaccine at 9 & 15 months of
      age.
AB  - BACKGROUND & OBJECTIVES: Measles, mumps and rubella (MMR) contribute to
      significant amount of mortality and morbidity in our country. Though MMR vaccine
      has been a part of immunization schedule in the developed countries, it is yet to
      be included in our national immunization schedule. Hence this study was conducted
      to assess the serological status of measles, mumps and rubella in young children
      and to evaluate the seroconversion of measles, mumps and rubella vaccine at 9 and
      15 months of age. METHODS: The cohort study was carried out at the out patient
      department of a tertiary care hospital in north India. A total of 240 normal
      children, 120 each in the age group 9-10 and 15-18 months attending the hospital
      for immunization were enrolled for the study. None of them had been vaccinated
      with MMR vaccine in the past, or gave any history of measles, mumps or rubella
      infection, or were on any immunosuppressive agent. The pre-vaccination blood
      sample was taken and each child was administered a single dose of trivalent MMR
      vaccine. The post-vaccination sample was taken 6-8 wk later. The paired serum
      samples were analysed for the presence of measles, mumps and rubella antibodies
      using commercially available ELISA kits. RESULTS: Of the 120 infants in the age
      group of 9-10 months, 102 (85%) were seronegative for measles and 96 (80%) were
      seronegative for both mumps and rubella. Following MMR vaccination, 102 infants
      came for post vaccination sampling of which 92 per cent were seropositive for
      measles, 100 per cent for mumps and 98 per cent for rubella. In the age group of
      15-18 months, of the 120 children, 67 (56%) were seronegative for measles, 84
      (70%) for mumps and 86 (71.6%) for rubella. In 50 per cent of the children, there
      was a history of measles immunization at 9 months of age. After MMR vaccination,
      100 children came for post vaccination sampling and seropositivity of 92, 96 and
      94 per cent was observed for measles, mumps and rubella, respectively. The rise
      in the pre- and post-immunization geometrical mean titre was significant (P <
      0.05) for each component of the vaccine in both the age groups. INTERPRETATION &
      CONCLUSION: The MMR vaccine can be offered safely and with equal efficacy to
      children at 9 and 15 months of age.

PMID- 14723483
TI  - Spectrum of beta-haemolytic streptococcal soft tissue infections at a tertiary
      care hospital of north india.
AB  - BACKGROUND & OBJECTIVES: An increase in the incidence of invasive beta haemolytic
      streptococcal infections has been observed in many Western countries. However,
      the role of beta-haemolytic streptococci in soft tissue infections is not well
      documented in developing countries. A retrospective study was carried out to
      review the spectrum of soft tissue infections caused by beta-haemolytic
      streptococci (betaHS) in a tertiary care hospital of north India. METHODS: The
      laboratory records of all patients with betaHS isolated from soft tissues between
      January 1996 and December 2000 were reviewed. Detailed clinical, laboratory and
      demographic data were recorded for all patients. RESULTS: A total of 39288
      samples from soft tissue infections were received in the bacteriology laboratory
      for bacterial culture during the study period. betaHS were recovered from 205
      samples. Of these, 56 per cent isolates were obtained from patients of suspected
      osteomyelitis. A seasonal pattern was observed with maximum isolation occuring in
      the winter months. Group A was the commonest isolate (75%), followed by group B
      Streptococcus (11%). Group C and G betaHS together accounted for about 3 per cent
      of all the isolates. All the isolates were sensitive to penicillin.
      INTERPRETATION & CONCLUSION: Soft tissue infections due to betaHS are common in
      our country. Group A streptococci were encountered most frequently with these
      infections though other groups of betaHS also contributed substantially. Since
      these infections are life threatening, there is a need to develop preventive,
      diagnostic and therapeutic strategies against betaHS.

PMID- 14723484
TI  - Antibacterial potential of an antispasmodic drug dicyclomine hydrochloride.
AB  - BACKGROUND & OBJECTIVES: Several compounds are known to possess antimicrobial
      activity in addition to their predesignated pharmacological actions. In the
      present study, dicyclomine hydrochloride, an antispasmodic drug, was tested for
      possible antimicrobial property in vitro and in vivo. METHODS: The minimum
      inhibitory concentration (MIC) of dicyclomine against the bacteria was determined
      by agar and broth dilution methods in vitro. The antibacterial activity of
      dicyclomine was confirmed by animal experiments. Toxicity and protective efficacy
      of the drug were tested in vivo. RESULTS: Dicyclomine inhibited most of the
      bacterial isolates tested at 25-100 microg/ml concentration, and a few were
      sensitive even at a lower concentration (10 microg/ml). Dicyclomine was found to
      be bacteriostatic in nature against Shigella dysenteriae 7, and bactericidal
      against S. aureus NCTC 6571, 8530, and 8531. When administered to Swiss white
      mice at doses of 30 and 60 microg/mouse, dicyclomine protected the animals
      challenged with 50 MLD of Salmonella typhimurium NCTC 74. INTERPRETATION &
      CONCLUSION: Dicyclomine showed inhibitory action against several pathogenic
      bacteria. It also offered significant protection to mice against the bacterial
      challange. As dicyclomine is in routine therapeutic use, it may be developed as a
      potent antimicrobial agent in many infections.

PMID- 14723485
TI  - Insulin levels in low birth weight neonates.
AB  - BACKGROUND & OBJECTIVES: Foetal undernutrition may have important role in adult
      insulin resistance and diabetes but insulin kinetics in very early life has not
      been well studied. The present study was undertaken to determine insulin levels
      in low birth weight neonates and compare with the levels in normal weight and
      high birth weight neonates. METHODS: Ten 7 day old children each of low birth
      weight (< 2500 g, Group 1), normal birth weight (2500-3500 g, Group 2) and high
      birth weight (> 3500 g, Group 3) selected successively over a period of one month
      were studied. All children were normally delivered at full term and were not
      suffering from any major illness. Detailed anthropometry was performed, a 6 h
      fasting blood sample was obtained for blood glucose, lipids, insulin and C
      peptide estimation; 60 min after an intravenous glucose load a second sample was
      obtained for glucose and insulin. Insulin resistance was calculated using the
      homeostasis model assessment (HOMA). RESULTS: Levels of total cholesterol,
      triglycerides, low density and high density lipoprotein cholesterol and glucose
      were not significantly different in the three groups. Mean fasting and post
      glucose load insulin levels (microU/ml) were 2.78 +/- 2.23 and 3.28 +/- 2.04 in
      Group 1, 1.67 +/- 1.20 and 2.60 +/- 2.32 in Group 2 and 3.37 +/- 2.08 and 4.40 +/
      3.05 in Group 3 and fasting C-peptide levels (microg/ml) were 0.296 +/- 0.22,
      0.208 +/- 0.09 and 0.327 +/- 0.23 respectively. There was no inter-group
      difference in insulin-glucose ratio, insulin levels adjusted for ponderal index
      and HOMA indices. A significant inverse quadratic correlation (U-shaped curve) of
      body weight with insulin (fasting and post-glucose) and C-peptide levels was
      observed (P < 0.05). INTERPRETATION & CONCLUSION: Both low and high birth weight
      term neonates have high fasting and post-glucose insulin levels. This U-shaped
      trend suggests influence of foetal undernutrition (environmental) as well as
      genetic factors in these children.

PMID- 14723486
TI  - Low levels of anti-histone antibodies in north Indian children with juvenile
      rheumatoid arthritis.
AB  - BACKGROUND & OBJECTIVES: Early onset pauciarticular disease with uveitis is
      distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA).
      The occurrence of anti-histone antibodies (AHA) in serum is strongly associated
      with presence of uveitis. There is a paucity of information from India on the
      levels of AHA in patients of JRA. In this study, an attempt was made to evaluate
      the levels of IgG and IgM antibodies to histones in children with JRA in north
      India. METHODS: Serum samples of 148 children with JRA (84 boys, 64 girls) were
      collected. Clinical details including onset, symptoms and course of the disease
      in each patient were recorded. Detailed eye examination including slit lamp
      examination was done in all patients at presentation and yearly thereafter to
      rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied
      by ELISA. Antinuclear antibodies (ANA) were measured by indirect
      immunofluorescence using HEP-2 cells as substrate at a screening dilution of
      1:40. RESULTS: Of the 148 children, 54 had pauciarticular (12 early onset and 42
      late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA
      were present in two children. AHA were raised in 15 (10%) children, of whom 10
      had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with
      early onset pauciarticular disease had uveitis, ANA or AHA. INTERPRETATION &
      CONCLUSION: The low occurrence of AHA and uveitis in our subset of patients with
      JRA is in contrast to that reported from Western countries. The low occurrence is
      unlikely due to technical reasons as the antigen that has been used consistently
      showed significant binding to serum from patients with systemic lupus
      erythematosus (SLE). This is in accordance with the rarity of early onset
      pauciarticular disease and chronic uveitis in these patients. More studies from
      other parts of the country are required to validate this observation.

PMID- 14723487
TI  - DNA linkage based diagnosis of Wilson disease in asymptomatic siblings.
AB  - BACKGROUND & OBJECTIVES: Wilson disease (WD) is an autosomal recessive disorder
      caused by defects in ATP7B gene located in chromosome 13q14, and manifested as
      hepatolenticular degeneration as a result of accumulation of copper. No
      information on the mutation in the ATP7B gene and haplotypes using linked markers
      is available for WD patients in India. Hence, the present study was undertaken to
      identify, by a PCR-based molecular diagnostic test, presymptomatic siblings of WD
      affected individuals in families with multiple offspring. METHODS: Genomic DNA
      was prepared from the peripheral blood of the patients, siblings and his/her
      first degree relatives. The repeat-markers flanking WD locus were amplified by
      PCR using fluorescent labeled primers. Amplified DNA fragments were analyzed by
      polyacrylamide gel electrophoresis in ABI 377 DNA sequencing system. Genotypes of
      the samples were determined using Genescan software. Haplotypes were determined
      based on segregation of the alleles in the families under study. RESULTS: Among
      15 WD affected families with multiple children, 4 cases were identified where
      younger siblings shared same genotype as the patient at all three markers
      analyzed. Further, eight different haplotypes were detected in the four patients.
      INTERPRETATION & CONCLUSION: The siblings of the WD patients carrying the same
      genotype at the markers linked to WD locus were presymptomatically diagnosed
      individuals. Presence of eight different haplotypes in the four patients
      suggested mutational heterogeneity at the WD locus. The test helps clinicians for
      therapeutic intervention in suspect WD cases by copper chelating agents prior to
      manifestation of overt clinical symptoms.

PMID- 14723488
TI  - Step response of mouse rod photoreceptors modeled in terms of elemental photic
      signals.
AB  - The process of light adaptation in rod photoreceptors enables these sensory cells
      of the retina to remain responsive to photic stimuli over a broad range of light
      intensity. Recent studies have employed the technique of paired-flash
      electroretinography to determine properties of phototransduction, and of light
      and dark adaptation, in rod photoreceptors in the living eye. Building on these
      studies, we have developed a theoretical model aimed at explaining the rod
      electrical response to a step of light based on known physiology. The central
      feature of the model is its description of the macroscopic (i.e., measured)
      response in terms of a time-evolving, weighted sum of elemental responses
      determined under dark-adapted and near fully light-adapted conditions. The model
      yields a time-dependent function that describes the course of desensitization and
      putatively represents the cumulative dynamics of underlying biochemical processes
      involved in light adaptation of the rod.

PMID- 14723489
TI  - Effects of electrode-to-fiber distance on temporal neural response with
      electrical stimulation.
AB  - This paper presents an analysis of the effects of the electrode-to-fiber distance
      on the temporal response properties of an auditory nerve fiber stimulated by
      electric current pulses. This analysis was based upon results from a
      computational model of a mammalian auditory nerve fiber axon having 50 nodes of
      Ranvier, each consisting of 130 stochastic sodium channels and 50 stochastic
      potassium channels, making it possible to represent the temporal fluctuations of
      action potential initiation and conduction. A monopolar stimulus electrode was
      located above a central (26th) node at electrode-to-fiber distances of 1, 4, and
      7 mm, while the recording electrode was located at the 36th node. Action
      potentials (spikes) were generated by the biophysical model using the Crank
      Nicholson method to solve a diffusive partial differential equation. By observing
      the occurrence times of spikes in response to 2000 cathodic monophasic stimulus
      pulses, temporal jitter (i.e., the standard deviation of spike times) was
      calculated and the poststimulus time (PST) histogram was generated as well.
      Furthermore, by computing the PST histogram for each initiation node as functions
      of space (node number) and time (PST), it was shown that spike initiation was
      distributed not only spatially but also temporally for stimulus levels producing
      firing efficiencies (FEs) near 0.5. However, at levels producing FEs near 0.99,
      while temporal variations approached zero, the spatial distribution of initiating
      nodes was comparable to that observed for the FE near 0.5. As temporal
      fluctuations are important for speech coding in cochlear implants, we conclude
      that spatial characteristics of the electrode-auditory nerve fiber interface may
      play a significant role in influencing these stochastic temporal processes.

PMID- 14723490
TI  - A three-dimensional kinematic and dynamic study of the lower limb during the
      stance phase of gait using an homogeneous matrix approach.
AB  - This paper presents a method to analyze three dimensional kinematics and dynamics
      of lower limb during walking. The proposed method is based on a homogeneous
      matrix concept, derived from robotics and using compact, expressive notation
      convenient for computer applications. The major advantage of this method is that
      no hypothesis is required on the joint model, which makes it applicable to
      complex and pathologic joints. Kinematic data are computed from 3-D trajectories
      of markers collected by a motion analysis system. External forces applied on the
      leg are measured synchronously during the stance phase of gait. Angular velocity
      components obtained using the homogeneous matrix method are displayed for three
      subjects and compared with those obtained from the same experimental data using a
      helical axis method. Then, intersegmental moments calculated from the inverse
      dynamic part of the homogeneous matrix method are shown on the same subjects.
      Kinematic results indicate that there are no significant differences between the
      methods, thus demonstrating the reproducibility of the stance phase of gait in
      the sagittal plane. Use of this synthetic homogeneous method developed for both
      kinematics and dynamics of rigid bodies demonstrates good promise for
      applications in biomechanics.

PMID- 14723491
TI  - Filament behavior in a computational model of ventricular fibrillation in the
      canine heart.
AB  - The aim of this paper was to quantify the behavior of filaments in a
      computational model of re-entrant ventricular fibrillation. We simulated cardiac
      activation in an anisotropic monodomain with excitation described by the Fenton
      Karma model with Beeler-Reuter restitution, and geometry by the Auckland canine
      ventricle. We initiated re-entry in the left and right ventricular free walls, as
      well as the septum. The number of filaments increased during the first 1.5 s
      before reaching a plateau with a mean value of about 36 in each simulation. Most
      re-entrant filaments were between 10 and 20 mm long. The proportion of filaments
      touching the epicardial surface was 65%, but most of these were visible for much
      less than one period of re-entry. This paper shows that useful information about
      filament dynamics can be gleaned from models of fibrillation in complex
      geometries, and suggests that the interplay of filament creation and destruction
      may offer a target for antifibrillatory therapy.

PMID- 14723492
TI  - Resonant spectra of malignant breast cancer tumors using the three-dimensional
      electromagnetic fast multipole model.
AB  - This paper presents an intensive numerical study of the resonance scattering of
      malignant breast cancer tumors. The three-dimensional electromagnetic model,
      based on the equivalence theorem, is used to obtain induced electric and magnetic
      currents on breast and tumor surfaces. The results show that the nonspherical
      malignant tumor can be characterized, based on its spectra, regardless of
      orientation, incident polarization, or incident or scattered directions. The
      spectra of the tumor depend solely upon its physical characteristics (i.e., shape
      and electrical properties); however, their locations are not functions of the
      depth of the tumor beneath the breast surface. This paper can be a guide in the
      selection of the frequency range at which the tumor resonates to produce the
      maximum signature at the receiver.

PMID- 14723493
TI  - Frequency domain simultaneous source and source coherence estimation with an
      application to MEG.
AB  - Interactions between cortical areas are crucial for cognitive functioning.
      Methods currently in use to assess such interactions are not well suited for this
      task because they lack timing precision, localization precision, or both. We
      present a method for simultaneous estimation of source location and orientation
      parameters and cross-spectral parameters to overcome these problems. Different
      estimators are evaluated for their performance. From a simulation study, we
      conclude that the estimators derived from the maximum-likelihood procedure have
      good statistical properties with moderate sample sizes, whereas those obtained
      from the generalized least squares procedure are biased and give poor-quality
      standard errors. The method is illustrated with visually evoked field data, with
      inconclusive results.

PMID- 14723494
TI  - Combined phase singularity and wavefront analysis for optical maps of ventricular
      fibrillation.
AB  - Much of the research into the mechanisms of ventricular fibrillation (VF) employs
      high-resolution mapping of electrical activation and recovery patterns. We
      previously developed a method for analyzing electrically mapped VF patterns that
      was based on identifying individual VF wavefronts. We now introduce a related
      method designed to take into account the information on repolarization that is
      present in optically mapped VF data. The new method first converts raw
      fluorescence data to an angular variable that tracks the phase of the mapped
      tissue through the depolarization-repolarization cycle. We define wavefronts in
      this context as isolines of phase that terminate either at boundaries or at
      singular points within the phase field. These singularities are the pivots of
      functional reentry and are important determinants of VF patterns. We parameterize
      VF by constructing data structures that describe wavefronts and singularities and
      also maintain wavefront-wavefront, wavefront-singularity, and singularity
      singularity relationships. We describe one important application of this
      parameterization, which is to identify, localize, and characterize the importance
      of occurrences of propagation block during VF.

PMID- 14723495
TI  - Detection of basal cell carcinoma using electrical impedance and neural networks.
AB  - Variations in electrical impedance over frequency might be used to distinguish
      basal cell carcinoma (BCC) from benign skin lesions, although the patterns that
      separate the two are nonobvious. Artificial neural networks (ANNs) may be good
      pattern classifiers for this application. A preliminary study to show the
      potential of neural networks to distinguish benign from malignant skin lesions
      using electrical impedance is presented. Electrical impedance was measured in
      vivo from 1 kHz to 1 MHz at five virtual depths on 18 BCC and 16 benign or
      premalignant lesions. A feed-forward neural network was trained using back
      propagation to classify these lesions. Two methods of preprocessing were used to
      account for the impedance of normal skin and the size of the lesion, one based on
      estimating the impedance of the lesion relative to adjacent normal skin and one
      based on estimating the impedance of the lesion independent of size or
      surrounding normal skin. Neural networks were able to classify measurements in a
      test set with 100% accuracy for the first preprocessing technique and 85%
      accuracy for the second. These results indicate electrical impedance may be a
      promising clinical diagnostic tool for basal cell carcinoma or other forms of
      skin cancer.

PMID- 14723496
TI  - Electrical impedance tomography using the extended Kalman filter.
AB  - In this paper, we propose an algorithm that, using the extended Kalman filter,
      solves the inverse problem of estimating the conductivity/resistivity
      distribution in electrical impedance tomography (EIT). The algorithm estimates
      conductivity/resistivity in a wide range. The purpose of this investigation is to
      provide information for setting and controlling air volume and pressure delivered
      to patients under artificial ventilation. We show that, when the standard
      deviation of the measurement noise level raises up to 5% of the maximal measured
      voltage, the conductivity estimates converge to the expected vector within 7%
      accuracy of the maximal conductivity value, under numerical simulations, with
      spatial a priori information. A two-phase identification procedure is proposed. A
      cylindrical phantom with saline solution is used for experimental evaluation. An
      abrupt modification on the resistivity distribution of this solution is caused by
      the immersion of a glass object. Estimates of electrode contact impedances and
      images of the glass object are presented.

PMID- 14723497
TI  - Prediction of ultrasound-mediated disruption of cell membranes using machine
      learning techniques and statistical analysis of acoustic spectra.
AB  - Although biological effects of ultrasound must be avoided for safe diagnostic
      applications, ultrasound's ability to disrupt cell membranes has attracted
      interest as a method to facilitate drug and gene delivery. This paper seeks to
      develop "prediction rules" for predicting the degree of cell membrane disruption
      based on specified ultrasound parameters and measured acoustic signals. Three
      techniques for generating prediction rules (regression analysis, classification
      trees and discriminant analysis) are applied to data obtained from a sequence of
      experiments on bovine red blood cells. For each experiment, the data consist of
      four ultrasound parameters, acoustic measurements at 400 frequencies, and a
      measure of cell membrane disruption. To avoid over-training, various combinations
      of the 404 predictor variables are used when applying the rule generation
      methods. The results indicate that the variable combination consisting of
      ultrasound exposure time and acoustic signals measured at the driving frequency
      and its higher harmonics yields the best rule for all three rule generation
      methods. The methods used for deriving the prediction rules are broadly
      applicable, and could be used to develop prediciton rules in other scenarios
      involving different cell types or tissues. These rules and the methods used to
      derive them could be used for real-time feedback about ultrasound's biological
      effects.

PMID- 14723498
TI  - Performance of an MEG adaptive-beamformer source reconstruction technique in the
      presence of additive low-rank interference.
AB  - The influence of external interference on neuromagnetic source reconstruction by
      adaptive beamformer techniques was investigated. In our analysis, we assume that
      the interference has the following two properties: First, it is additive and
      uncorrelated with brain activity. Second, its temporal behavior can be
      characterized by a few distinct activities, and as a result, the spatio-temporal
      matrix of the interference has a few distinctly large singular values. Namely,
      the interference can be modeled as a low-rank signal. Under these assumptions,
      our analysis shows that the adaptive beamformer techniques are insensitive to
      interference when its spatial singular vectors are so different from a lead field
      vector of a brain source that the generalized cosine between these two vectors is
      much smaller than unity. Four types of numerical examples verifying this
      conclusion are presented.

PMID- 14723499
TI  - Sequential characterization of atrial tachyarrhythmias based on ECG time
      frequency analysis.
AB  - A new method for characterization of atrial arrhythmias is presented which is
      based on the time-frequency distribution of an atrial electrocardiographic
      signal. A set of parameters are derived which describe fundamental frequency,
      amplitude, shape, and signal-to-noise ratio. The method uses frequency-shifting
      of an adaptively updated spectral profile, representing the shape of the atrial
      waveforms, in order to match each new spectrum of the distribution. The method
      tracks how well the spectral profile fits each spectrum as well as if a valid
      atrial signal is present. The results are based on the analysis of a learning
      database with signals from 40 subjects, of which 24 have atrial arrhythmias, and
      an evaluation database with 211 patients diagnosed with atrial fibrillation. It
      is shown that the method robustly estimates fibrillation frequency and amplitude
      and produces spectral profiles with narrower peaks and more discernible harmonics
      when compared to the conventional power spectrum. The results suggest that a
      rather strong correlation exist between atrial fibrillation frequency and f wave
      shape. The developed set of parameters may be used as a basis for automated
      classification of different atrial rhythms.

PMID- 14723500
TI  - Predictive scheduling algorithms for real-time feature extraction and spatial
      referencing: application to retinal image sequences.
AB  - Real-time spatial referencing is an important alternative to tracking for
      designing spatially aware ophthalmic instrumentation for procedures such as laser
      photocoagulation and perimetry. It requires independent, fast registration of
      each image frame from a digital video stream (1024 x 1024 pixels) to a spatial
      map of the retina. Recently, we have introduced a spatial referencing algorithm
      that works in three primary steps: 1) tracing the retinal vasculature to extract
      image feature (landmarks); 2) invariant indexing to generate hypothesized
      landmark correspondences and initial transformations; and 3) alignment and
      verification steps to robustly estimate a 12-parameter quadratic spatial
      transformation between the image frame and the map. The goal of this paper is to
      introduce techniques to minimize the amount of computation for successful spatial
      referencing. The fundamental driving idea is to make feature extraction
      subservient to registration and, therefore, only produce the information needed
      for verified, accurate transformations. To this end, the image is analyzed along
      one-dimensional, vertical and horizontal grid lines to produce a regular sampling
      of the vasculature, needed for step 3) and to initiate step 1). Tracing of the
      vascular is then prioritized hierarchically to quickly extract landmarks and
      groups (constellations) of landmarks for indexing. Finally, the tracing and
      spatial referencing computations are integrated so that landmark constellations
      found by tracing are tested immediately. The resulting implementation is an order
      of-magnitude faster with the same success rate. The average total computation
      time is 31.2 ms per image on a 2.2-GHz Pentium Xeon processor.

PMID- 14723501
TI  - Elliptic cylinder geometry for distinguishability analysis in impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is a technique that computes the cross
      sectional impedance distribution within the body by using current and voltage
      measurements made on the body surface. It has been reported that the image
      reconstruction is distorted considerably when the boundary shape is considered to
      be more elliptical than circular as a more realistic shape for the measurement
      boundary. This paper describes an alternative framework for determining the
      distinguishability region with a finite measurement precision for different
      conductivity distributions in a body modeled by elliptic cylinder geometry. The
      distinguishable regions are compared in terms of modeling error for predefined
      inhomogeneities with elliptical and circular approaches for a noncircular
      measurement boundary at the body surface. Since most objects investigated by EIT
      are noncircular in shape, the analytical solution for the forward problem for the
      elliptical cross section approach is shown to be useful in order to reach a
      better assessment of the distinguishability region defined in a noncircular
      boundary. This paper is concentrated on centered elliptic inhomogeneity in the
      elliptical boundary and an analytic solution for this type of forward problem.
      The distinguishability performance of elliptical cross section with cosine
      injected current patterns is examined for different parameters of elliptical
      geometry.

PMID- 14723502
TI  - A radio-telemetry system with a shape memory alloy microelectrode for neural
      recording of freely moving insects.
AB  - A radio frequency (RF) telemetry system with a shape memory alloy microelectrode
      was designed and fabricated. The total size and weight are 15 mm x 8 mm and 0.1
      g, respectively. Since the telemeter is small and light enough to be loaded on a
      small animal such as an insect, the system can be used for the neural recording
      of a freely moving insect. The RF-telemeter can transmit signals by frequency
      modulation transmission at 80-90 MHz. The transmitted signals can be received up
      to about 16 meters away from the telemeter with a high signal-to-noise ratio. The
      neural activity can be detected without attenuation by using an instrumentation
      amplifier with its input impedance set to 2 Mohms at 1 kHz. The telemeter was
      loaded on a cockroach and the neural activity during a free-walk was successfully
      measured through this telemetry system.

PMID- 14723503
TI  - Characterization of implantable microfabricated fluid delivery devices.
AB  - The formal characterization of the performance of microfluidic delivery devices
      is crucial for reliable in vivo application. A comprehensive laboratory technique
      was developed and used to optimize, calibrate and validate microfabricated fluid
      delivery devices. In vivo experiments were carried out to verify the accuracy and
      reliability of the pressure driven devices. Acute guinea pig experiments were
      conducted to measure the response to alpha-amino-3-hydroxy-5-methyl-4-isoxalone
      propionic acid, an excitatory neurotransmitter, at multiple locations in the
      inferior colliculus. A nondimensional parameter, Q, was successfully used to
      classify devices in terms of geometry alone (i.e., independent of fluid
      properties). Functional devices exhibited long-term linearity and reliability in
      delivering single phase, Newtonian fluids, in discrete volumes with a resolution
      of 500 picoliters at less than 0.45 lbf/in2 (30 mbar) pressure drop. Results for
      non-Newtonian fluids are not presented here. The acute results showed a
      proportional increase in the firing rate for delivered volumes of 2 nL up to 10
      nL (at rates of between 0.1 and 1 nL/s). Flow characteristics are maintained
      during acute experiments and post-implant. A control experiment conducted with
      Ringer solution produced negligible effects, suggesting the results to be truly
      pharmacological. The experimental techniques employed have proven to be reliable
      and will be used for future calibration and testing of next generation chronic
      microfluidic delivery devices.

PMID- 14723504
TI  - Long-term stimulation and recording with a penetrating microelectrode array in
      cat sciatic nerve.
AB  - We studied the consequences of long-term implantation of a penetrating
      microelectrode array in peripheral nerve over the time course of 4-6 mo.
      Electrode arrays without lead wires were implanted to test the ability of
      different containment systems to protect the array and nerve during contractions
      of surrounding muscles. Treadmill walking was monitored and the animals showed no
      functional deficits as a result of implantation. In a different set of
      experiments, electrodes with lead wires were implanted for up to 7 mo and the
      animals were tested at 2-4 week intervals at which time stimulation thresholds
      and recorded sensory activity were monitored for every electrode. It was shown
      that surgical technique highly affected the long-term stimulation results.
      Results between measurement sessions were compared, and in the best case, the
      stimulation properties stabilized in 80% of the electrodes over the course of the
      experiment (162 days). The recorded sensory signals, however, were not stable
      over time. A histological analysis performed on all implanted tissues indicated
      that the morphology and fiber density of the nerve around the electrodes were
      normal.

PMID- 14723505
TI  - Gold-coated microelectrode array with thiol linked self-assembled monolayers for
      engineering neuronal cultures.
AB  - We report the use of a gold coating on microelectrode arrays (MEAs) to enable the
      use of the relatively reliable surface modification chemistry afforded by
      alkanethiol self-assembled monolayers (SAMs). The concept is simple and begins
      with planar MEAs, which are commercially available for neuronal cell culture and
      for brain slice studies. A gold film, with an intermediate adhesive layer of
      titanium, is deposited over the insulation of an existing MEA in a manner so as
      to be thin enough for transmission light microscopy as well as to avoid
      electrical contact to the electrodes. The alkanethiol-based linking chemistry is
      then applied for the desired experimental purpose. Here we show that polylysine
      linked to alkanethiol SAM can control the geometry of an in vitro hippocampal
      neuronal network grown on the MEA. Furthermore, recordings of neuronal action
      potentials from random and patterned networks suggest that the gold coating does
      not significantly alter the electrode properties. This design scheme may be
      useful for increasing the number of neurons located in close proximity to the
      electrodes. Realization of in vitro neuronal circuits on MEAs may significantly
      benefit basic neuroscience studies, as well as provide the insight relevant to
      applications such as neural prostheses or cell-based biosensors. The gold coating
      technique makes it possible to use the rich set of thiol-based surface
      modification techniques in combination with MEA recording.

PMID- 14723506
TI  - Extracellular and intracellular volume variations during postural change measured
      by segmental and wrist-ankle bioimpedance spectroscopy.
AB  - Extracellular (ECW) and intracellular (ICW) volumes were measured using both
      segmental and wrist-ankle (W-A) bioimpedance spectroscopy (5-1000 kHz) in 15
      healthy subjects (7 men, 8 women). In the 1st protocol, the subject, after
      sitting for 30 min, laid supine for at least 30 min. In the second protocol, the
      subject, who had been supine for 1 hr, sat up in bed for 10 min and returned to
      supine position for another hour. Segmental ECW and ICW resistances of legs, arms
      and trunk were measured by placing four voltage electrodes on wrist, shoulder,
      top of thigh and ankle and using Hanai's conductivity theory. W-A resistances
      were found to be very close to the sum of segmental resistances. When switching
      from sitting to supine (protocol 1), the mean ECW leg resistance increased by
      18.2%, that of arm and W-A by 12.4%. Trunk resistance also increased but not
      significantly by 4.8%. Corresponding increases in ICW resistance were smaller for
      legs (3.7%) and arm (-0.7%) but larger for the trunk (21.4%). Total body ECW
      volumes from segmental measurements were in good agreement with W-A and Watson
      anthropomorphic correlation. The decrease in total ECW volume (when supine)
      calculated from segmental resistances was at 0.79 l less than the W-A one (1.12
      l). Total ICW volume reductions were 3.4% (segmental) and 3.8% (W-A). Tests of
      protocol 2 confirmed that resistance and fluid volume values were not affected by
      a temporary position change.

PMID- 14723507
TI  - Accuracy limitations of chronaxie values.
AB  - The strength-duration curve is a plot of the threshold current (I) versus pulse
      duration (d) required to stimulate excitable tissue. On this curve are two
      points: 1) rheobase (b) and 2) chronaxie (c). Rheobase is the threshold current
      for an infinitely long-duration stimulus. Chronaxie, the excitability constant,
      is the duration of a pulse of current of twice rheobasic strength. The
      mathematical expression for the strength-duration curve is I = b(1 + c/d).
      Although there are many published values for chronaxie for various excitable
      tissues, the range of variability for a given tissue type is quite large. This
      paper identifies five factors that can affect the accuracy of chronaxie
      measurement and shows that the most reliable values can be obtained with a
      rectangular pulse delivered from a constant-current source.

PMID- 14723508
TI  - Time-frequency detection and analysis of wheezes during forced exhalation.
AB  - The objective of the present work was to detect and analyze wheezes by means of a
      highly sensitive time-frequency algorithm. Automatic measurements were compared
      with clinical auscultation for forced exhalation segments from 1.2 to 0
      liters/second (l/s). Sensitivities between 100% and 71%, as a function of flow
      level related to wheezing segments detection, were achieved. Time-frequency
      wheeze parameters were measured for the flow range from 1.2 to 0.2 l/s. Wheezes
      were detected in both analyzed groups; asthmatics (N = 16) and control subjects
      (N = 15). Significant differences between groups were found for the mean number
      of wheezes detected at basal condition (p = 0.0003). Frequency parameter
      differences were also significant (0.0112 < p < 0.0307). All these parameters
      were also studied after applying a bronchodilator drug (Terbutaline). Significant
      differences between patient groups were found when studying the changes in the
      number of wheezes for each patient (p = 0.0195). Finally, limited bandwidth
      parameters, which measure the bronchodilator response, were also studied.

PMID- 14723509
TI  - Real-time digital signal processing-based optical coherence tomography and
      Doppler optical coherence tomography.
AB  - We present the development and use of a real-time digital signal processing (DSP)
      based optical coherence tomography (OCT) and Doppler OCT system. Images of
      microstructure and transient fluid-flow profiles are acquired using the DSP
      architecture for real-time processing of computationally intensive calculations.
      This acquisition system is readily configurable for a wide range of real-time
      signal processing and image processing applications in OCT.

PMID- 14723510
TI  - Signal processing methodology to study the cutaneous vasodilator response to a
      local external pressure application detected by laser Doppler flowmetry.
AB  - The existence of a cutaneous pressure-induced vasodilation (PIV) has recently
      been reported. This paper proposes a signal processing methodology to improve PIV
      knowledge. Temporal variations of laser Doppler signals rhythmic activities are
      first analyzed on anesthetized rats. The results lead to a method that provides a
      better PIV understanding.

PMID- 14723511
TI  - The natural frequencies of the arterial system and their relation to the heart
      rate.
AB  - We assume the major function of the arterial system is transporting energy via
      its transverse vibration to facilitate the blood flowing all the way down to the
      microcirculation. A highly efficient system is related to maintaining a large
      pressure pulse along the artery for a given ventricular power. The arterial
      system is described as a composition of many infinitesimal Windkessels. The
      strong tethering in the longitudinal direction connects all the Windkessels
      together and makes them vibrate in coupled modes. It was assumed that at rest
      condition, the arterial system is in a steady distributed oscillatory state,
      which is the superposition of many harmonic modes of the transverse vibration in
      the arterial wall and the adherent blood. Every vibration mode has its own
      characteristic frequency, which depends on the geometry, the mass density, the
      elasticity, and the tethering of the arterial system. If the heart rate is near
      the fundamental natural frequency, the system is in a good resonance condition,
      we call this "frequency matching." In this condition, the pulsatile pressure wave
      is maximized. A pressure wave equation derived previously was used to predict
      this fundamental frequency. The theoretical result gave that heart rate is
      proportional to the average high-frequency phase velocity of the pressure wave
      and the inverse of the animal body length dimension. The area compliance related
      to the efficiency of the circulatory system is also mentioned.

PMID- 14723512
TI  - Quantifying ventricular fibrillation: in silico research and clinical
      implications.
AB  - Cardiovascular disease remains the leading cause of death in otherwise healthy
      humans. In particular, most cases of sudden cardiac death occur as a result of
      failure of the mechanical function of the heart which is triggered by a turbulent
      pattern of electrical excitation of the heart e.g., ventricular fibrillation
      (VF). Although the exact mechanisms of VF remain unknown, increasing evidence
      indicates that it is organized by multiple reentrant sources (wavelets).

PMID- 14723513
TI  - On tubes, strings, and resonance in the arterial system--what makes the beat go
      on?

PMID- 14723514
TI  - Does a sterically bulky group occupy the equatorial site in trigonal bipyramidal
      phosphorus?
AB  - [structure: see text] The sterically bulky tert-butyl group occupies an apical
      position in trigonal bipyramidal phosphorus in the compound [CH2(6-t-Bu-4-Me
      C6H2O)2]P(t-Bu)(1,2-O2C6Cl4) in contrast to the occupation of an equatorial
      position by the small methyl group in [CH2(6-t-Bu-4-Me-C6H2O)2]P(Me)(1,2
      O2C6Cl4); this observation contradicts the familiar "apicophilicity rules" for
      trigonal bipyramidal phosphorus. Low-temperature solution 31P NMR spectra of
      [CH2(6-t-Bu-4-Me-C6H2O)2]P(R)(1,2-O2C6Cl4) (R = Me, Et, and n-Bu) show the
      presence of more than two isomers.

PMID- 14723515
TI  - The first total synthesis of 15-deoxy-Delta12,14-prostaglandin J2 and the
      unambiguous assignment of the C14 stereochemistry.
AB  - [reaction: see text] The first total synthesis of 15-deoxy-Delta12,14
      prostaglandin J2 is reported. The highly unsaturated cyclopentenone prostaglandin
      was obtained via a silicon-tethered allenic [2 + 2 + 1] cycloaddition reaction
      developed in our group. In addition, the stereochemistry at C14 has been assigned
      unambiguously.

PMID- 14723516
TI  - Asymmetric hydrocyanation of hydrazones catalyzed by lanthanide--PYBOX complexes.
AB  - [reaction: see text] The asymmetric addition of HCN to hydrazones is catalyzed in
      high yield and good-to-excellent enantioselectivity by the easily prepared
      (PhPYBOX)ErCl3 complex. This constitutes the first example of asymmetric
      catalytic hydrocyanation of hydrazones.

PMID- 14723517
TI  - Lambertellols A and B, novel 3,4-dihydronaphthalen-1(2H)-ones with spiro
      butenolide produced by Lambertella sp.1346.
AB  - [structure: see text] Lambertella sp. 1346 was found to produce lambertellols A
      (1) and B (2) carrying a novel dihydronaphthalen-1(2H)-ones with spiro-1-furan
      2(5'H)-one. The spiro-lactone ring moiety of both 1 and 2 were easily migrated to
      afford lambertellin, a known metabolite of Lambertella corni-maris. The absolute
      stereochemistry of these compounds was established on the basis of CD spectrum
      after chemical derivatization.

PMID- 14723519
TI  - Synthetic approaches to guanacastepenes. Enantiospecific syntheses of BC and AB
      ring systems of guanacastepenes and rameswaralide.
AB  - [reaction: see text] A simple and efficient approach for the BC and AB ring
      systems of the novel diterpenes guanacastepenes and rameswaralide starting from
      the readily and abundantly available monoterpene (R)-carvone employing RCM
      reaction as the key step is described.

PMID- 14723518
TI  - "Endo" and "exo" bicyclo[4.2.0]-octadiene isomers from the electrocyclization of
      fully substituted tetraene models for SNF 4435C and D. control of stereochemistry
      by choice of a functionalized substituent.
AB  - [reaction: see text] A tandem electrocyclic closure, perceived as the key step in
      a biomimetic approach to SNF 4435C and D, was tested with 1,1,8-trisubstituted
      tetraene substrates. The ratio of endo:exo products could be controlled by the
      choice of the RZ substituent at C-1. On the basis of these results, a short
      stereoselective route to an advanced SNF 4435 intermediate was devised.

PMID- 14723520
TI  - Efficient heterogeneous asymmetric transfer hydrogenation of ketones using highly
      recyclable and accessible silica-immobilized Ru-TsDPEN catalysts.
AB  - [reaction: see text] Chiral Ru-TsDPEN [N-(p-toluenesulfonyl)-1,2
      diphenylethylenediamine]-derived catalysts were first successfully immobilized
      onto amorphous silica gel and mesoporous silicas of MCM-41 and SBA-15 by an
      easily accessible approach. The catalyst immobilized on silica gel demonstrated
      remarkably high catalytic activities and excellent enantioselectivities (up to
      >99% ee) for the heterogeneous asymmetric transfer hydrogenation of various
      ketones. Particularly, the catalyst could be readily recovered and reused in
      multiple consecutive catalytic runs (up to 10 uses) with the completely
      maintained enantioselectivity.

PMID- 14723521
TI  - First seco-C oleananes from nature.
AB  - [structure: see text] The triterpenes 8,14-seco-oleana-8(26),13-dien-3beta-ol (1)
      and its acetyl derivative 2 were isolated from Stevia viscida and Stevia
      eupatoria, respectively. Their structures were elucidated by 2D NMR, including
      carbon-carbon connectivity experiments, and confirmed by X-ray diffraction
      analysis of ketone 3. The absolute configuration was determined by NMR analysis
      of the Mosher esters of 1. The biogenetic implications of the new substances are
      discussed.

PMID- 14723522
TI  - Enhancing the enantioselectivity of an epoxide hydrolase by directed evolution.
AB  - [reaction: see text] The epoxide hydrolase (EH) from Aspergillus niger, which
      shows a selectivity factor of only E = 4.6 in the hydrolytic kinetic resolution
      of glycidyl phenyl ether, has been subjected to directed evolution for the
      purpose of enhancing enantioselectivity. After only one round of error-prone
      polymerase chain reaction (epPCR), enantioselectivity was more than doubled (E =
      10.8). The improved mutant enzyme contains three amino acid exchanges, two of
      which are spatially far from the catalytically active center.

PMID- 14723523
TI  - Efficient modulation of hydrogen-bonding interactions by remote substituents.
AB  - [structure: see text] A series of tetralactam macrocycles having different
      substituents were prepared, and their binding affinities for an adipamide guest
      were investigated in CDCl3 by 1H NMR titrations. The association constants
      strongly depend on the substituents, varying up to DeltaDeltaG = 3.4 kcal/mol;
      electron-donating substituents (OMe, NMe2) decrease the binding affinity, while
      electron-withdrawing groups (Cl, NO2) increase it. These large substituent
      effects have been rationalized by secondary repulsions and partial perturbations
      of intramolecular hydrogen bonds.

PMID- 14723524
TI  - Modes of binding interaction between viologen guests and the cucurbit[7]uril
      host.
AB  - [structure: see text] Host-guest interactions between cucurbit[7]uril (CB7) and a
      series of dialkyl-4,4'-bipyridinium (viologen) dicationic guests were
      investigated by NMR spectroscopy. CB7 includes the aromatic nucleus of short
      chain viologens, but the mode of interaction is different with longer chain
      viologens due to the favorable hydrophobic interactions between the terminal
      alkyl substituents and the inner cavity of the host. A new pseudorotaxane was
      designed and synthesized on the basis of viologen-CB7 binding interactions.

PMID- 14723525
TI  - Origin of stereochemical reversal in Meyers-type enolate alkylations. Importance
      of intramolecular Li coordination and solvent effects.
AB  - [reaction: see text] The origin of exclusive exo-stereochemistry in the
      alkylation of Meyers-type enolate 2 has been studied. It was found that the
      intramolecular complex with a strong Li...O(ring) interaction (the O-complex) may
      be responsible as the major enolate species in tetrahydrofuran (THF). The
      transition state of the O-complex leading to exo-stereochemistry is found to be
      the most favorable process in THF.

PMID- 14723526
TI  - Tandem RCM of dienynes for the construction of taxol-type carbocyclic systems.
AB  - [reaction: see text] Tandem ring-closing metathesis of hydrindanone dienynes
      allows access to taxosteroids, a new class of compounds that combine the [5.3.1]
      carbocyclic system of taxanes with rings C and D of the steroid skeleton.

PMID- 14723527
TI  - Aza-Michael addition of nosyloxycarbamates to 2-(trifluoromethyl)acrylates.
AB  - [reaction: see text] The amination of 2-(trifluoromethyl)acrylates, performed by
      nosyloxycarbamates, gives two different aminated products, the derivatives of
      alpha-trifluoromethyl beta-amino esters or the aziridines, in high yields by
      changing the reaction conditions. The aza-Michael addition product was isolated
      for the first time in this kind of reaction. This finding confirms the aza-MIRC
      mechanism we previously proposed. Asymmetric induction was also pursued.

PMID- 14723528
TI  - Acyl vs sulfonyl transfer in N-acyl beta-sultams and 3-oxo-beta-sultams.
AB  - [reaction: see text] N-Acylsulfonamides usually react with nucleophiles by acyl
      transfer and C-N bond fission. However, the hydrolysis of N-acyl beta-sultams is
      a sulfonyl transfer reaction that occurs with S-N fission and opening of the four
      membered ring. Similar to other beta-sultams, the N-acyl derivatives are at least
      10(6)-fold more reactive than N-acyl sulfonamides. 3-Oxo-beta-sultams are both
      beta-lactams and beta-sultams but also hydrolyze with preferential S-N bond
      fission.

PMID- 14723529
TI  - Olefin metathesis: remote substituents governing the stereoselectivity of 11
      membered-ring formation.
AB  - [reaction: see text] Stereospecific RCM reaction of 7 (R1 = Me) results in the
      formation of (Z)-11-membered macrocycle 9c. Cascade RCM/ROM/RCM transformation of
      7 (R1 = H) affords the thermodynamically more stable spirocycle product 12.

PMID- 14723530
TI  - Synthesis and protection of aryl sulfates using the 2,2,2-trichloroethyl moiety.
AB  - [reaction: see text] The 2,2,2-trichloroethyl (TCE) group was utilized as the
      first protecting group for aryl sulfates. Aryl sulfates, protected with the TCE
      group, were prepared in high yield by reacting phenols with chlorosulfuric acid
      TCE ester. Deprotection was accomplished using Pd/C-ammonium formate or with Zn
      ammonium formate to give aryl sulfate monoesters in high yield. This approach to
      aryl sulfate synthesis was successfully applied to the construction of estrone
      sulfate derivatives, which could not be prepared by previous methodologies.

PMID- 14723531
TI  - An efficient synthesis of a probe for protein function: 2,3-diaminopropionic acid
      with orthogonal protecting groups.
AB  - [reaction: see text] An efficient and cost-effective synthesis of N(alpha)-Boc2
      N(beta)-Cbz-2,3-diaminopropionic acid is reported. The synthesis starts from
      commercially available N(alpha)-Boc-Asp(OBn)-OH and employs a Curtius
      rearrangement to establish the beta-nitrogen. Proper protection of the alpha
      nitrogen is essential for the success of the Curtius rearrangement.

PMID- 14723532
TI  - Novel vanadium-catalyzed oxidation of alcohols to aldehydes and ketones under
      atmospheric oxygen.
AB  - [reaction: see text] Oxidation of alcohols to aldehydes and ketones has been
      studied in high yields using atmospheric oxygen and a catalytic amount of V2O5 in
      toluene under heating (ca. 100 degrees C). Secondary alcohols can be
      chemoselectively converted into ketones in the presence of primary hydroxy
      groups.

PMID- 14723533
TI  - Synthesis of a novel C2-symmetric thiourea and its application in the Pd
      catalyzed cross-coupling reactions with arenediazonium salts under aerobic
      conditions.
AB  - [reaction: see text] A novel thiourea-based C2-symmetric ligand was synthesized,
      and its application in the palladium-catalyzed Heck and Suzuki coupling reactions
      of arenediazonium salts was evaluated. The reactions, which were performed at
      room temperature, without added base, and under aerobic conditions, produced
      product in 4 h with good yield. The corresponding arenediazonium salts were
      easily generated in one step from anilines.

PMID- 14723534
TI  - Efficient aqueous-phase Heck and Suzuki couplings of aryl bromides using tri(4,6
      dimethyl-3- sulfonatophenyl)phosphine trisodium salt (TXPTS).
AB  - [reaction: see text] Sterically demanding, sulfonated arylphosphines TXPTS and
      TMAPTS have been applied to the aqueous-phase Heck and Suzuki coupling of aryl
      bromides. TXPTS provides good yields of Heck coupling products from aryl bromides
      at 80 degrees C, while both TMAPTS and TPPTS gave significantly less active
      catalysts. TXPTS is the first ligand to promote the aqueous-phase Heck coupling
      under such mild conditions. Both TXPTS and TMAPTS provide active catalysts for
      Suzuki couplings of aryl bromides at 50 degrees C.

PMID- 14723535
TI  - Hydrogen bond-induced rigid oligoanthranilamide ribbons that are planar and
      straight.
AB  - [structure: see text] A new series of oligoanthranilamides has been synthesized
      starting from suitably modified p-phenylenediamine and p-phthalic acid
      derivatives. Due to strong intramolecular three-center hydrogen bonds, the new
      oligomers self-assemble into highly stable straight and planar molecular ribbons,
      which have been characterized by X-ray crystallography and 1H NMR, IR, and UV-vis
      spectroscopy.

PMID- 14723536
TI  - cADPR analogues: effect of an adenosine 2'- or 3'-methoxy group on conformation.
AB  - [structure: see text] The 2'-OMe-A (2) and 3'-OMe-A (3) analogues of the calcium
      release agent cADPR (1) were prepared and their solution structures studied by
      NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and
      changes in its R ring N:S and gammat:gamma+ ratios, while 3 displays a
      significant change in the conformation of its A ring gamma-bond.

PMID- 14723537
TI  - A synthesis of the diazonamide heteroaromatic biaryl macrocycle/hemiaminal core.
AB  - [reaction: see text] Stille coupling of an arylstannane aminal 19 with the
      palladium complex 23 leads to atropisomeric esters 28 and 29. Conversion to
      macrocycle 30 is demonstrated, a potential precursor of natural and unnatural
      diazonamides.

PMID- 14723538
TI  - Differential and substrate-selective reactivity of calix[4]arene derivatives with
      cyclenyl-Zn(II) modifications at the upper rim.
AB  - [structure: see text] Novel "cone conformation" calix[4]arene derivatives,
      carrying either one or two cyclen (1,4,7,10-tetra-azacyclododecane) moieties at
      the upper rim, have been synthesized. The hydrolytic activities of the Zn(II)
      complexes of these calixarenes were studied. A surprising behavior was observed
      with p-nitrophenylstearate; whereas the bis-cyclenyl-2Zn(II) complex showed
      negligible hydrolytic activity over the background, the mononuclear complex
      showed a significant 400-fold rate increase at pH 8.5.

PMID- 14723539
TI  - Efficient synthesis of DNA containing the guanine oxidation-nitration product 5
      guanidino-4-nitroimidazole: generation by a postsynthetic substitution reaction.
AB  - [reaction: see text] A convertible nucleoside was synthesized and used to prepare
      the 2'-deoxynucleoside of 5-guanidino-4-nitroimidazole, a putative in vivo
      product of the reaction of peroxynitrite with guanine. The convertible nucleoside
      was incorporated into an oligodeoxynucleotide by the phosphoramidite method and
      converted postsynthetically to yield an oligodeoxynucleotide containing 5
      guanidino-4-nitroimidazole at a specific site. The oligodeoxynucleotide was
      inserted into a viral genome. Melting temperature analysis revealed that duplexes
      containing 5-guanidino-4-nitroimidazole were greatly destabilized relative to
      unmodified duplexes.

PMID- 14723540
TI  - Regiospecific, enantiospecific total synthesis of the 12-alkoxy-substituted
      indole alkaloids, (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine,
      and (-)-fuchsiaefoline.
AB  - [reaction: see text] The enantiospecific synthesis of 7-methoxy-d-tryptophan was
      completed by combination of the Larock heteroannulation process with a Schollkopf
      based chiral auxiliary in good yield. This ester was then employed in the first
      total synthesis of (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine,
      and (-)-fuchsiaefoline in regiospecific, stereospecific fashion in excellent
      overall yield. The asymmetric Pictet-Spengler reaction and enolate-driven
      palladium-catalyzed cross coupling processes served as key steps.

PMID- 14723541
TI  - Enantioselective reactions of scalemic acyclic alpha-(alkoxy)alkyl- and alpha-(N
      carbamoyl)alkylcuprates.
AB  - [reaction: see text] Scalemic acyclic alpha-(alkoxy)alkyl- and alpha-(N
      carbamoyl)alkylcuprates prepared from organostannanes via organolithium reagents
      react with vinyl iodides, propargyl mesylates, and alpha,beta-enones to afford
      coupled products with enantioselectivities ranging from 0 to 99% ee depending
      upon cuprate reagent, substrate structure, solvent, and temperature. In general,
      lithium cuprates give higher chemical yields and lower enantioselectivities,
      while the trends are reversed for the corresponding zinc cuprate reagents.

PMID- 14723542
TI  - Efficient oxidative radical cyclizations of ester enolates with carbocation
      desilylation as termination: synthesis of cyclopentanoid monoterpenes and
      analogues.
AB  - [reaction: see text] An efficient oxidative radical cyclization approach for the
      synthesis of 2-alkenyl cyclopentane or cyclohexane carboxylates from omega
      silylallyl ester enolates induced by recyclable SET oxidant ferrocenium
      hexafluorophosphate has been developed. A new tandem
      alkoxycarbonylation/oxidative radical cyclization/cationic termination process
      forms the basis for a five-step synthesis of the cyclopentanoid monoterpene
      dihydronepetalactone and analogues.

PMID- 14723543
TI  - Bolaforms with fourteen galactose units: a proposed site-directed cohesion of
      cancer cells.
AB  - [structure: see text] The multistep synthesis of a calixarene joined to a second
      calixarene via a long spacer is described. Since each calixarene bears multiple
      galactose-based units (known to bind strongly to rat hepatoma cells), there
      existed the possibility of cross-linking the cancer cells into a network. The
      compounds did not serve this purpose, a fact potentially correctable by adjusting
      or rigidifying the spacer. Formation of a "cancer net" around a solid tumor
      remains a viable approach to retarding growth and/or inhibiting metastasis.

PMID- 14723544
TI  - Toward homogeneity of chirality via selective formation of homochiral or
      heterochiral aggregates.
AB  - [reaction: see text] A new method of achieving homogeneity of chirality via
      purification of nonracemic (partially resolved) amino alcohols 1a-d and the C2
      chiral diamine 2 to obtain samples of higher ee, through preparation of
      homochiral and heterochiral aggregates using oxalic and fumaric acids, is
      described.

PMID- 14723545
TI  - Alpha-hydroxylation at C-15 and C-16 in cholesterol: synthesis of (25R)-5alpha
      cholesta-3beta,15alpha,26-triol and (25R)-5alpha-cholesta-3beta,16alpha,26-triol
      from diosgenin.
AB  - [reaction: see text] (25R)-5alpha-cholesta-3beta,16alpha,26-triol 7b and (25R)
      5alpha-cholesta-3beta,15alpha,26-triol 10b were synthesized, via (25R)-5alpha
      cholesta-3beta,16beta,26-triol 5a, from diosgenin 3 in 52% yield over six steps
      and 47% yield over eight steps, respectively. An efficient method for inversion
      of a C-16beta hydroxyl to the C-16alpha position and a short method for
      transposition of a C-16beta hydroxyl to the C-15alpha position via the unexpected
      beta-reduction of a C-15 ketone in a steroid are reported.

PMID- 14723546
TI  - Planarized star-shaped oligothiophenes with enhanced pi-electron delocalization.
AB  - [structure: see text] Planarized star-shaped oligothiophenes 1 have been
      synthesized by connecting short-chain oligothiophenes on a benzo[1,2-b:3,4-b':5,6
      b' ']trithiophene central core. Their electrochemical and optical properties have
      been characterized by cyclic voltammetry and UV-visible spectroscopy,
      respectively. These results associated with theoretical calculations show the
      advantage of benzotrithiophene as a central core in terms of pi-electron
      delocalization.

PMID- 14723547
TI  - Expedient synthesis of highly substituted fused heterocoumarins.
AB  - [reaction: see text] Highly substituted fused coumarins can be prepared in two
      steps starting from the appropriate boronic acids and enol triflates. The
      synthesis of fused pyrano[2,3-d]pyrimidin-7-one (1) is a key example to
      demonstrate the potential of the method in the elaboration of new coumarin
      scaffolds.

PMID- 14723548
TI  - Asymmetric allylic amination in water catalyzed by an amphiphilic resin-supported
      chiral palladium complex.
AB  - [reaction: see text] Catalytic asymmetric allylic amination of cycloalkenyl
      carbonates (methyl cyclohexen-2-yl carbonate, methyl cyclohepten-2-yl carbonate,
      methyl 5-methoxycarbonylcyclohexen-2-yl carbonate, methyl cyclohexenyl carbonate,
      tert-butyl 5-methoxycarbonyloxy-1,2,5,6-tetrahydropyridinedicarboxylate) with
      dibenzylamines ((C6H5CH2)2NH, (C6H5CH2)(4-CH3OC6H4CH2)NH, (4-CH3OC6H4CH2)2NH) was
      achieved in water under heterogeneous conditions by use of a palladium complex of
      (3R,9aS)-3-[2-(diphenylphosphino)phenyl]-2-phenyltetrahydro-1H-imidazo[1,5
      a]indole-1-one anchored on polystyrene-poly(ethylene glycol) copolymer resin to
      give the corresponding cycloalkenylamines with high enantiomeric selectivity (90
      98% ee).

PMID- 14723549
TI  - Comparison of photoelectron transfer in solution and the solid state for two
      intervalence radical cations.
AB  - [structure: see text] The optical diffuse reflectance and solution spectra of two
      bis-hydrazine radical cationic intervalence compounds have been compared. The
      results are consistent with an ion-pairing increase and an "effective polarity"
      in these crystals that is not far from that of acetonitrile or other polar
      solvents.

PMID- 14723550
TI  - Alkenes as ketol surrogates-a new approach toward enantiopure acyloins.
AB  - [reaction: see text] Enantiopure alpha-hydroxy ketones are important building
      blocks in organic synthesis. This paper describes the use of cyclic ruthenates
      for the first catalytic regioselective oxidation of vic-diols to alpha-ketols.
      The combination of RuCl3/Oxone/NaHCO3 was used in a two-step sequence of
      asymmetric dihydroxylation and regioselective monooxidation for the synthesis of
      a broad scope of enantiopure acyloins.

PMID- 14723551
TI  - Magnesiation employing Grignard reagents and catalytic amine. Application to the
      functionalization of N-phenylsulfonylpyrrole.
AB  - [reaction: see text] N-Phenylsulfonylpyrrole 1 is magnesiated by treatment with
      isopropylmagnesium chloride and catalytic diisopropylamine. Reaction with various
      electrophiles, including palladium-catalyzed aryl- and heteroaryl cross-coupling,
      provides 2-substituted phenylsulfonylpyrroles in moderate to good yields.

PMID- 14723552
TI  - Enantioselective access to 2,7-cis-disubstituted oxepanes: formal synthesis of
      (+)-isolaurepan.
AB  - [reaction: see text] The asymmetric synthesis of 2,7-cis-disubstituted oxepanes
      bearing a sulfoxide is achieved from commercially available precursors in only
      five steps. The key step is the highly diastereoselective Et3SiH/TMSOTf-promoted
      reductive cyclization of enantiopure hydroxysulfinyl aryl or alkyl ketones.

PMID- 14723553
TI  - A new and efficient method for the synthesis of trifluoromethylthio- and
      selenoethers.
AB  - [reaction: see text] A new atom-economic procedure for preparation of
      trifluoromethyl thio- and selenoethers is reported, wherein both halves of aryl
      and alkyl disulfides and diselenides are able to be utilized with high
      efficiency.

PMID- 14723554
TI  - Rhodium-catalyzed asymmetric 1,6-addition of aryltitanates to enynones giving
      axially chiral allenes.
AB  - [reaction: see text] The addition of aryltitanate reagents ArTi(OPr-i)4Li to 3
      alkynyl-2-en-1-ones in the presence of chlorotrimethylsilane and a rhodium-(R)
      segphos as a catalyst proceeded in a 1,6-fashion to give a high yield of axially
      chiral allenylalkenyl silyl enol ethers with up to 93% ee.

PMID- 14723555
TI  - Cannabinoids in multiple sclerosis: do they have a therapeutic role?
AB  - This is an exciting time for cannabinoid research. Evidence suggests that
      cannabis (marijuana) can alleviate symptoms like muscle spasticity and pain in
      patients with multiple sclerosis (MS). Interest in the field of cannabinoids has
      been strengthened by the identification and cloning of cannabinoid receptors
      located in the central nervous system and the peripheral immune organs, and by
      the discovery of the endogenous cannabinoid ligands. Cannabinoids are also
      efficacious in animal models of MS. However, there have been only ten published
      clinical reports on the use of cannabis in MS, involving 78 individuals
      worldwide, and the results have been equivocal. Researchers encounter a number of
      difficulties in designing clinical studies that use cannabinoids. From the
      studies reporting the use of cannabinoids in MS patients with spasticity, the
      somewhat better designed studies failed to demonstrate objective improvement.
      Therefore, convincing evidence that cannabinoids are effective in MS is still
      lacking.

PMID- 14723556
TI  - Phosphodiesterase 5 inhibitors in rapid ejaculation: potential use and possible
      mechanisms of action.
AB  - Rapid (premature) ejaculation (RE) is a very common sexual disorder. This
      condition may be primary or secondary to underlying disease. Control of RE has
      been primarily focused on behavioural therapy, topical anaesthetics, tricyclic
      antidepressants and selective serotonin reuptake inhibitors; however, an approved
      treatment does not exist. Recently, a number of clinical trials have studied the
      potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in
      the treatment of RE. Results of most of these studies have been encouraging.
      Available data indicate that there is clinical, anatomical, physiological,
      pharmacological and genetic evidence to explain the efficacy of PDE5 inhibitors
      in RE. The rationale for the use of PDE5 inhibitors in the treatment of RE could
      be due to possible peripheral and central mechanisms. Possible peripheral
      ejaculation retarding capabilities may include modulation of the contractile
      response of the vas deferens (VD), seminal vesicles (SV), prostate and urethra,
      induction of a state of peripheral analgesia, and prolongation of the total
      duration of erection. Possible central mechanisms may involve lessening of the
      central sympathetic output. Furthermore, there is evidence from knockout mice to
      explain the efficacy of PDE5 inhibitors in RE. Mice lacking the gene for
      endothelial nitric oxide synthase develop a condition similar to RE. On the other
      hand, mice lacking the gene for heme oxygenase-2 develop a condition similar to
      delayed ejaculation. This review also discusses the findings against the use of
      these agents in RE. In conclusion, a review of the literature suggests the
      potential usefulness of PDE5 inhibitors as a promising line of therapy in RE but
      further studies are needed.

PMID- 14723557
TI  - First-line treatment strategies to improve survival in patients with advanced
      colorectal cancer.
AB  - Advanced colorectal cancer is a significant cause of worldwide cancer-related
      mortality. For the majority of patients, palliative chemotherapy can yield
      substantial improvements in survival. Fluorouracil has been the mainstay of
      treatment in this setting for the past few decades. The relatively recent
      availability of new combinations with active agents such as irinotecan and
      oxaliplatin makes this a promising and hopeful time for the treatment of
      metastatic colorectal cancer, with median survivals now approaching 18-21 months.
      For patients presenting with resectable metastases, the goal of therapy is
      surgery with a curative intent. There exists the potential for this approach to
      be extended also to a greater proportion of patients whose cancer may be rendered
      resectable following effective neoadjuvant chemotherapy. In addition, an improved
      understanding of molecular predictors for treatment response and toxicity may
      facilitate the future selection of individualised treatments for a given tumour
      profile. Further improvements in the management of advanced disease will continue
      to be pursued through the ongoing development of multimodality approaches and the
      incorporation of novel targeted agents with innovative chemotherapy combinations.

PMID- 14723558
TI  - Myofascial pain disorders: theory to therapy.
AB  - Voluntary muscle is the largest human organ system. The musculotendinous
      contractual unit sustains posture against gravity and actuates movement against
      inertia. Muscular injury can occur when soft tissues are exposed to single or
      recurrent episodes of biomechanical overloading. Muscular pain is often
      attributed to a myofascial pain disorder, a condition originally described by Drs
      Janet Travell and David Simons. Among patients seeking treatment from a variety
      of medical specialists, myofascial pain has been reported to vary from 30% to 93%
      depending on the subspecialty practice and setting. Forty-four million Americans
      are estimated to have myofascial pain; however, controversy exists between
      medical specialists regarding the diagnostic criteria for myofascial pain
      disorders and their existence as a pathological entity. Muscles with activity or
      injury-related pain are usually abnormally shortened with increased tone and
      tension. In addition, myofascial pain disorders are characterised by the presence
      of tender, firm nodules called trigger points. Within each trigger point is a
      hyperirritable spot, the 'taut-band', which is composed of hypercontracted
      extrafusal muscle fibres. Palpation of this spot within the trigger point
      provokes radiating, aching-type pain into localised reference zones. Research
      suggests that myofascial pain and dysfunction with characteristic trigger points
      and taut-bands are a spinal reflex disorder caused by a reverberating circuit of
      sustained neural activity in a specific spinal cord segment. The treatment of
      myofascial pain disorders requires that symptomatic trigger points and muscles
      are identified as primary or ancillary pain generators. Mechanical, thermal and
      chemical treatments, which neurophysiologically or physically denervate the
      neural loop of the trigger point, can result in reduced pain and temporary
      resolution of muscular overcontraction. Most experts believe that appropriate
      treatment should be directed at the trigger point to restore normal muscle length
      and proper biomechanical orientation of myofascial elements, followed by
      treatment that includes strengthening and stretching of the affected muscle.
      Chronic myofascial pain is usually a product of both physical and psychosocial
      influences that complicate convalescence.

PMID- 14723559
TI  - The glycylcyclines: a comparative review with the tetracyclines.
AB  - The tetracycline class of antimicrobials exhibit a broad-spectrum of activity
      against numerous pathogens, including Gram-positive and Gram-negative bacteria,
      as well as atypical organisms. These compounds are bacteriostatic, and act by
      binding to the bacterial 30S ribosomal subunit and inhibiting protein synthesis.
      The tetracyclines have been used successfully for the treatment of a variety of
      infectious diseases including community-acquired respiratory tract infections and
      sexually transmitted diseases, as well in the management of acne. The use of
      tetracyclines for treating bacterial infections has been limited in recent years
      because of the emergence of resistant organisms with efflux and ribosomal
      protection mechanisms of resistance. Research to find tetracycline analogues that
      circumvented these resistance mechanisms has lead to the development of the
      glycylcyclines. The most developed glycylcycline is the 9-tert-butyl-glycylamido
      derivative of minocycline, otherwise known as tigecycline (GAR-936). The
      glycylcyclines exhibit antibacterial activities typical of earlier tetracyclines,
      but with more potent activity against tetracycline-resistant organisms with
      efflux and ribosomal protection mechanisms of resistance. The glycylcyclines are
      active against other resistant pathogens including methicillin-resistant
      staphylococci, penicillin-resistant Streptococcus pneumoniae, and vancomycin
      resistant enterococci. Tigecycline is only available in an injectable formulation
      for clinical use unlike currently marketed tetracyclines that are available in
      oral dosage forms. Tigecycline has a significantly larger volume of distribution
      (> 10 L/kg) than the other tetracyclines (range of 0.14 to 1.6 L/kg). Protein
      binding is approximately 68%. Presently no human data are available describing
      the tissue penetration of tigecycline, although studies in rats using
      radiolabelled tigecycline demonstrated good penetration into tissues. Tigecycline
      has a half-life of 36 hours in humans, less than 15% of tigecycline is excreted
      unchanged in the urine. On the basis of available data, it does not appear that
      the pharmacokinetics of tigecycline are markedly influenced by patient gender or
      age. The pharmacodynamic parameter that best correlates with bacteriological
      eradication is time above minimum inhibitory concentration. Several animal
      studies have been published describing the efficacy of tigecycline. Human phase 1
      and 2 clinical trials have been completed for tigecycline. Phase 2 studies have
      been conducted in patients with complicated skin and skin structure infections,
      and in patients with complicated intra-abdominal infections have been published
      as abstracts. Both studies concluded that tigecycline was efficacious and well
      tolerated. Few human data are available regarding the adverse effects or drug
      interactions resulting from tigecycline therapy; however, preliminary data report
      that tigecycline can be safely used, is well tolerated and that the adverse
      effects experienced were typical of the tetracyclines (i.e. nausea, vomiting and
      headache). Tigecycline appears to be a promising new antibacterial based on in
      vitro and pharmacokinetic/pharmacodynamic activity; however more clinical data
      are needed to fully evaluate its potential.

PMID- 14723565
TI  - Heparin-induced thrombocytopenia and graft thrombosis following endovascular
      aneurysm repair.
AB  - PURPOSE: To report a case of heparin-induced thrombocytopenia (HIT) complicated
      by stent-graft thrombosis. CASE REPORT: An 82-year-old woman underwent
      endovascular aortic aneurysm repair using a Zenith stent-graft. She returned 2
      weeks later with an occluded graft limb, large quantities of thrombus lining the
      remainder of the stent-graft, thrombocytopenia, and antiplatelet antibodies.
      There were no signs of kinking or compression of the graft, nor was there any
      thrombosis of the native arteries downstream from the occluded graft limb.
      Thrombolysis restored graft patency. Anticoagulation was induced using hirudin
      and warfarin. The graft remains patent at 6-month follow-up. CONCLUSION: HIT is a
      rare cause of postoperative endograft thrombosis. In this case, the presumed
      source of the inciting heparin dosage was the stent-graft itself, which had been
      soaked in a concentrated heparin solution prior to insertion.

PMID- 14723561
TI  - Cetuximab: in the treatment of metastatic colorectal cancer.
AB  - Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal
      growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal
      cancer tumours and associated with advanced disease. Cetuximab induces a broad
      range of cellular responses in tumours expressing EGFR, enhancing sensitivity to
      radiotherapy and chemotherapeutic agents. In a large, randomised, open-label,
      multicentre study in adult patients with irinotecan-refractory, metastatic
      colorectal cancer expressing EGFR, cetuximab 400 mg/m2 initial dose followed by
      250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of
      partial response and disease control (partial response plus stable disease), and
      increased time to disease progression, compared with cetuximab monotherapy;
      survival was similar in both groups. The same dosage of cetuximab combined with
      irinotecan, fluorouracil and folinic acid (various regimens) produced partial
      responses in 43-58% of patients, a complete response in 5% of patients (one study
      only) and stable disease in 32-52% of patients with treatment-naive metastatic
      colorectal cancer expressing EGFR in three small, open-label trials. The most
      common grade 3/4 adverse events associated with cetuximab monotherapy were acne
      like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving
      cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and
      neutropenia.

PMID- 14723560
TI  - Hypopigmentary skin disorders: current treatment options and future directions.
AB  - Alterations of skin and hair pigmentation are important features that have
      warranted treatment from ancient history on up to modern time. In some cultures,
      even today patients with vitiligo are regarded as social outcasts and are
      affected considerably both emotionally and physically. This article presents
      current options and future directions for the treatment of hypopigmentary
      disorders. Whereas with congenital disorders, such as albinism and
      phenylketonuria, no causal therapy has been established up to now, several
      treatment options for acquired hypopigmentary disorders have been investigated.
      In particular, in vitiligo, one of the most prevalent hypopigmentary disorders, a
      number of treatment modalities have been employed in the past 30 years. However,
      most of them are only able to palliate, not cure, the disease. Depending on the
      distribution of the hypopigmented lesions (localised or generalised) and the
      state of the disease (active or stable), several therapeutic options, for example
      phototherapy, surgical skin grafts, autologous melanocyte transplantation and
      immunomodulators, can be applied alone or in combination. For phototherapy,
      because of unfavourable results and adverse effects, ultraviolet (UV) A has been
      largely replaced by narrow-band UVB for repigmentation of generalised vitiligo.
      Although immunomodulators, such as corticosteroids, have been used both topically
      and systemically over the past 3 decades for the treatment of disseminated
      vitiligo, they are only suitable for the treatment of acrofacial and localised
      forms because of adverse effects. Hence, new immunomodulatory agents, such as
      calcineurin antagonists, have recently been introduced as new promising tools to
      treat acquired hypopigmentary disorders. However, all therapeutic approaches are
      hampered by the fact that the pathophysiology of hypopigmentary disorders is
      still poorly understood.

PMID- 14723566
TI  - Internal iliac artery occlusion using a stent-graft tunnel during endovascular
      aneurysm repair: a new alternative to coil embolization.
AB  - PURPOSE: To report a new endovascular technique for internal iliac artery (IIA)
      occlusion during stent-graft treatment in patients with aortoiliac aneurysm.
      TECHNIQUE: Stent-grafts measuring 20 to 28 mm in diameter and 37.5 mm long were
      deployed at the iliac bifurcation to occlude the IIA at its origin. Subsequent
      deployment of an aortic bifurcation endograft with ipsilateral extension into the
      external iliac artery was through this iliac stent-graft tunnel. This approach
      has been used in 5 patients with abdominal aortic aneurysm and common iliac
      artery aneurysm (n=4) or isolated iliac artery aneurysm. Proximal IIA occlusion
      was achieved in all cases with no distal type I endoleak. IIA patency on the side
      opposite to the tunnel procedure was preserved in each case. No patient described
      new onset of pelvic ischemic symptoms. Over a mean 10-month follow-up (range 1
      12), there was no secondary procedure required for type I endoleak. Three
      patients had a CIA aneurysm diameter change of -1, -4, and 0 mm at 1 year.
      CONCLUSIONS: This new method for IIA occlusion at its origin without coil
      embolization may prove to be a useful adjunct to endovascular aortoiliac aneurysm
      repair. The technique is simple, rapid, and may minimize the risk of pelvic
      ischemia.

PMID- 14723567
TI  - Coil embolization of iliac artery aneurysms developing after abdominal aortic
      aneurysm repair with a conventional bifurcated graft.
AB  - PURPOSE: To evaluate the efficacy of embolizing iliac artery aneurysms (IAAs)
      developing after abdominal aortic aneurysm (AAA) repair. METHODS: The records of
      6 patients (5 men; mean age 79 years, range 61-87) with unilateral (n=3) or
      bilateral (n=3) IAAs that had developed after AAA repair were reviewed. In all
      patients, the limbs of the bifurcated graft were anastomosed end-to-end or end-to
      side with the external iliac arteries during AAA repair. Before embolization,
      superior mesenteric artery (SMA) arteriography was done in all patients to
      evaluate collateral pathways to the inferior mesenteric artery (IMA). RESULTS:
      The unilateral IAAs were treated by proximal and distal embolization. In 2
      patients with bilateral IAAs, SMA angiography showed sufficient collateral flow
      to the IMA, so the aneurysms were treated by proximal embolization and packing.
      In the other bilateral IAA case, the left 6-cm IAA was treated by proximal and
      distal embolization, while the contralateral 3-cm IAA was not embolized because
      angiography demonstrated inadequate collateral flow to the IMA, indicating a
      possible risk of colon ischemia if both IAAs were embolized. Immediate
      postprocedural angiography in all patients showed complete exclusion of the IAAs.
      Mild buttock claudication occurred in 1 patient. There were no episodes of
      rupture over a mean 46-month follow-up. CONCLUSIONS: Embolization is a safe and
      effective alternative to open surgery for the treatment of IAAs that develop
      after AAA repair. However, before embolization, angiographic evaluation of
      collateral pathways to the IMA is essential to reduce the risk of colon ischemia.

PMID- 14723568
TI  - Endovascular aortic arch reconstruction with supra-aortic transposition for
      symptomatic contained rupture and dissection: early experience in 8 high-risk
      patients.
AB  - PURPOSE: To report our initial experience with total and subtotal endovascular
      aortic arch reconstruction combined with supra-aortic vessel transposition in
      high-risk patients and to present a new morphological classification of thoracic
      aortic lesions for patient and procedure selection. METHODS: Among 80 patients
      treated with thoracic stent-grafts at our department between 1997 and 2003, 8
      patients (6 men; mean age 71 years, range 45-81) unfit for open repair were not
      candidates for standard endovascular repair due to inadequate proximal landing
      zones on the aortic arch. Commercially available endografts (Excluder, Zenith,
      Endofit, Talent) were used to repair the arch after supra-aortic vessel
      transposition was performed. The endograft was implanted transfemorally or via an
      iliac Dacron conduit graft with standardized endovascular techniques and deployed
      during intravenous adenosine-induced asystole. The imaging data from all thoracic
      endograft patients was analyzed to classify thoracic and thoracoabdominal lesions
      according to a 4-level anatomical system. RESULTS: Deployment success was 100%
      after staged supra-aortic vessel transposition, but 1 patient died of endograft
      related rupture of the proximal aortic arch. There was no neurological
      complication. Mean follow-up was 16 months (range 1-36). Patency of all
      endografts and conventional bypasses was 100%, and no migration was observed. One
      minor type II endoleak was demonstrated. CONCLUSIONS: Initial results are
      encouraging for endovascular aortic arch repair in combination with supra-aortic
      transposition in selected high-risk patients with complex aortic pathologies.

PMID- 14723569
TI  - Patency rates of femorofemoral bypasses associated with endovascular aneurysm
      repair surpass those performed for occlusive disease.
AB  - PURPOSE: To evaluate the patency rates of femorofemoral grafts performed in
      conjunction with aortomonoiliac or aortomonofemoral (AMI/F) endografts. METHODS:
      Over the past 8 years, 110 patients (98 men; mean age 77+/-7 years, range 57-90)
      underwent aortoiliac aneurysm repair with an AMI/F endograft. Follow-up data in
      these patients were prospectively collected for a mean 2.3 years (range 1-68
      months). RESULTS: There were 2 early (<7 days) AMI/F endograft thromboses with
      secondary femorofemoral graft occlusion. In both patients, patency of all grafts
      was restored by thrombectomy plus stenting of the endograft. Three late (4, 5,
      and 10 months) AMI/F endograft thromboses led to femorofemoral graft failure; 2
      were successfully treated, but the third patient refused further intervention. No
      femorofemoral bypass failed in the absence of AMI/F endograft thrombosis. There
      were no femorofemoral graft infections. Four-year life-table primary and
      secondary patency rates were 95% and 99%, respectively. CONCLUSIONS:
      Femorofemoral bypasses with AMI/F endografts for aneurysmal disease are durable
      procedures and have better patency than femorofemoral grafts used to treat
      occlusive disease. Femorofemoral bypass patency rates alone are not a
      disadvantage of aortomonoiliac endografts.

PMID- 14723570
TI  - Incidence of renal infarctions after endovascular AAA repair: relationship to
      infrarenal versus suprarenal fixation.
AB  - PURPOSE: To analyze the incidence and etiology of renal infarctions following
      endovascular abdominal aortic aneurysm (AAA) repair detected on computed
      tomography (CT) and determine any association with infrarenal versus suprarenal
      fixation. METHODS: Between August 1994 and October 2001, 663 patients (604 men;
      mean age 68.5 years, range 40-98) underwent endovascular AAA repair with
      predominately bifurcated (505, 77%) stent-grafts. About a third (202, 30%) of the
      devices were deployed in a suprarenal position. Contrast-enhanced CT scans were
      performed on days 10, 90, and 365 after operation and then annually. Two
      radiologists blinded to procedural details compared the preoperative and
      postoperative scans to identify renal infarctions from inadvertent renal artery
      occlusion by the endograft. Only patients with inadvertent infarctions were
      analyzed relative to endograft fixation position and stent-graft type. RESULTS:
      Mean follow-up was 37 months (range 0.1-75). Overall renal infarction rate was
      11.9% (n=79); 23 (3.4%) patients suffered from limited, segmental infarction due
      to intentional covering of preoperatively diagnosed accessory renal arteries.
      Unintentional renal ischemia was identified in 56 (8.5%) patients. In this
      subgroup, 39 (19%) were observed in the 202 patients with suprarenal fixation
      versus 17 (3.7%) in the 461 stent-grafts positioned infrarenally (RR 3.35, 95% CI
      2.20 to 5.04, p<0.00001). There was a significant correlation between the
      incidence of infarction and the device type (14.3% for modular grafts versus 5.6%
      for unibody designs, p=0.0002). Seventeen (2.6%) patients suffered from
      unilateral kidney loss, with dialysis required in 2 cases. Creatinine and urea
      showed no significant postoperative elevation in the overall patient population,
      but both levels were significantly (p<0.02) elevated in patients with complete
      unilateral renal infarcts. CONCLUSIONS: Transrenal fixation of aortic endografts
      had a 3-fold higher risk for renal infarction in this large patient population.
      There is no significant difference for specific endografts, but modular designs
      were associated with a higher rate of renal infarction. The need to occlude
      preoperatively diagnosed accessory renal arteries with an endograft should be
      considered a contraindication for current available devices.

PMID- 14723571
TI  - Angioplasty/stenting of the superior mesenteric artery and celiac trunk: early
      and late outcomes.
AB  - PURPOSE: To analyze the early results and durability of angioplasty/stenting of
      the superior mesenteric artery (SMA) and celiac trunk (CT). METHODS: Twenty-two
      patients (19 women; mean age 69.2 years, range 52-88) with 24 symptomatic SMA or
      CT stenotic lesions were treated with dilation/stenting over a recent 4.5-year
      period. Two patients had lesions in both the SMA and CT treated. Clinical follow
      up and duplex exams were done to evaluate long-term patency. Kaplan-Meier life
      table analyses estimated the freedom from recurrent stenosis and recurrent
      symptoms, as well as survival rates. RESULTS: The initial technical and clinical
      success rates were 96% (23/24) and 95% (21/22), respectively, with no
      perioperative mortality or major morbidity. During a mean follow-up of 26 months
      (range 1-54), the primary late clinical success rate was 61% (11/18; 4 lost to
      follow-up), and freedom from recurrent stenosis (> or =70%) was 30% (6/20). The
      freedom from recurrent stenosis at 1, 2, 3, and 4 years were 65%, 47%, 39%, and
      13%; freedom from recurrent symptoms was 67% at all 4 intervals. The survival
      rates were 93%, 93%, 80%, and 53% at 1 to 4 years, respectively. CONCLUSIONS:
      Angioplasty/stenting of SMA and CT stenoses has a high initial technical success
      rate and acceptable early and late clinical outcomes; however, it is associated
      with a high incidence of late restenosis based on strict Doppler criteria.

PMID- 14723572
TI  - Filter devices for cerebral protection during carotid angioplasty and stenting.
AB  - The risk of embolization during carotid artery stenting (CAS) has been the
      foremost reason for the cautious acceptance of this percutaneous alternative to
      carotid endarterectomy. To address this issue, numerous embolic protection
      devices are being evaluated as an adjunct to CAS for neuroprotection. Among the 3
      main categories of these devices, distal filters, which trap embolic debris while
      maintaining distal cerebral perfusion, have attracted the most corporate
      interest. This review focuses on the emerging field of embolic protection filters
      for use in CAS.

PMID- 14723573
TI  - Determinants of in-stent restenosis after carotid angioplasty: a case-control
      study.
AB  - PURPOSE: To report a retrospective study that sought to identify clinical factors
      contributing to the development of in-stent restenosis in the carotid arteries,
      to profile the patients at greatest risk, and to review the treatment modalities
      evolved from our experience. METHODS: Between December 2000 and April 2003, 195
      carotid angioplasty/stenting (CAS) procedures (12 bilateral) were performed in
      183 patients (131 men; median age 65.9 years, interquartile range 55.2-72.7).
      Stenting for de novo stenoses was performed in 119 (61%) carotid arteries; 76
      (39%) vessels were treated for postsurgical restenosis. Nearly two thirds of the
      patients (117, 64%) were symptomatic. Patients were evaluated at 3 and 6 months
      and at 6-month intervals thereafter with duplex ultrasonography. Angiography was
      used to confirm any recurrent lesion detected on the ultrasound scan. RESULTS:
      Overall perioperative neurological complications included 4 (2.2%) minor strokes,
      1 (0.5%) intracranial hemorrhage, and 1 (0.5%) major stroke; both patients with
      major neurological complications died at 5 and 12 days, respectively, after the
      procedure. During the 12.5-month follow-up (range 0-27.2), 3 non-procedure
      related late deaths and another 9 (4.9%) neurological events occurred (2 strokes
      and 7 transient ischemic attacks). In-stent restenosis after CAS was present in
      10 (5.2%) of 193 carotid arteries (9/181 patients) in follow-up; all but 1 artery
      had been treated for postsurgical restenosis. All lesions were treated
      secondarily with endovascular procedures. Statistical analysis demonstrated that
      postsurgical restenosis was the only predictive factor for the development of in
      stent restenosis (OR 15.5, 95% CI 2.05 to 125.6, p=0.001) in this cohort.
      CONCLUSIONS: The present study, far from being exhaustive on the subject,
      indicates that patients who develop restenosis after carotid endarterectomy are
      also prone to develop restenosis after CAS; moreover, although strongly
      recommended for postsurgical restenosis, CAS carries a greater risk of in-stent
      restenosis in this subgroup, thus reducing the benefits of this procedure.

PMID- 14723574
TI  - Carotid revascularization using endarterectomy or stenting systems (CARESS):
      phase I clinical trial.
AB  - PURPOSE: To determine whether carotid stenting with embolic protection is
      equivalent to carotid endarterectomy (CEA) in a broad risk population of patients
      with symptomatic and asymptomatic carotid stenosis. METHODS: A prospective,
      multicenter Phase I trial was conducted comparing standard CEA to carotid
      stenting systems (CSS) in patients with symptomatic (> or =50%) and asymptomatic
      (> or =75%) carotid stenosis. Patients were enrolled using selection criteria
      reflective of broad clinical practice. The enrollment ratio at each clinical site
      was designed to be 2:1 (CEA to CSS) to achieve a planned enrollment of 450
      patients: 300 in the CEA arm and 150 in the CSS cohort, which would ensure
      adequate precision with a coefficient of variation < or =0.35. The primary
      endpoint for comparison was 30-day all-cause mortality and nonfatal stroke.
      RESULTS: Between April 2001 and December 2002, 14 clinical sites enrolled 439
      patients, of which 397 (247 men; mean age 71 years, range 44-89) were treated:
      254 with CEA and 143 patients with CSS (ratio 1.8 to 1.0). More than 90% of
      patients had >75% stenosis; approximately 68% of patients were asymptomatic.
      There were no significant differences in baseline patient characteristics between
      the treatment groups with the exception of a more frequent history of prior CEA
      (30% CSS versus 11% for CEA, p<0.0001) and prior carotid stent placement in the
      CSS group (6% versus 0% for CEA, p=0.0002). There was no significant difference
      in the 30-day combined all-cause mortality and stroke rate by Kaplan-Meier
      estimate between CEA (2%) and CSS (2%). There was no significant difference in
      the secondary endpoint of combined 30-day all-cause mortality, stroke, and
      myocardial infarction between CEA (3%) and CSS (2%). CONCLUSIONS: This study
      suggests that the 30-day risk of stroke or death following carotid stenting with
      cerebral protection is equivalent to standard carotid endarterectomy in a broad
      risk population of patients with carotid stenosis.

PMID- 14723576
TI  - Vascular occlusion by ruptured balloon after percutaneous transluminal
      angioplasty.
AB  - PURPOSE: To report a rare case of chronic vascular occlusion by an undetected
      ruptured balloon fragment following percutaneous transluminal angioplasty. CASE
      REPORT: A 79-year-old man suffered from calf claudication 1 year after
      angioplasty for a short stenosis in the superficial femoral artery. During the
      femoropopliteal bypass operation, a ruptured angioplasty balloon was retrieved.
      CONCLUSIONS: Endovascular treatment of arterial lesions always requires thorough
      pre and postinterventional check of the applied instrumentation. A damaged
      catheter must initiate an immediate search for lost intravascular objects.

PMID- 14723575
TI  - Effects of excess and deprivation of serotonin on in vitro neuronal
      differentiation.
AB  - The neurotransmitter serotonin (5HT) possesses developmental functions in
      vertebrates and invertebrates. Rodent embryos express 5HT receptors even before
      neural development, but the role of this neurochemical seems to be particularly
      important during axonal morphogenesis and differentiation and in neural crest
      cell migration. Moreover, 5HT inhibitors are teratogenic in mammals, inducing
      brain and heart abnormalities. The aim of this study was to investigate the
      effects of nonphysiological concentrations of 5HT (5HT excess as well as
      deprivation) on developing rat neural cells using the micromass method. This
      simple and rapid micromass method allows the culture of mesencephalic cells
      capable of achieving and maintaining a significant degree of differentiation.
      Mesencephalic cells from 13 d post coitum (pc) rat were cultured and exposed to
      exogenous 5HT (1, 10, 50, or 100 microM) or to the specific 5HT2 receptor
      inhibitor mianserin (0.5, 5, 25, or 50 microM) during the whole culture period (5
      d). The micromass morphology, the cytoskeletal organization, the pathological
      apoptosis, and the differentiative capability of cultured mesencephalic cells
      have been analyzed. The results show that 10-100 microM 5HT and 0.5-50 microM
      mianserin are able to disrupt the normal micromass morphology; 5HT and mianserin
      are unable to interfere with the cytoskeletal structures; mianserin (but not 5HT)
      induces pathological apoptosis on micromass cells at concentration levels of 0.5
      50 microM; 5HT (but not mianserin) alters the neural differentiation at
      concentration levels of 10-100 microM. In conclusion, our results demonstrate
      that an excess of 5HT inhibits the capability of mesencephalic neurons to
      differentiate as shown by the alterations of the expression of the neuronal
      differentiative proteins glial-derived neurotrophic factor and Neu-N; on the
      other hand, the blocking of 5HT2 receptors induces apoptosis in differentiating
      neurons.

PMID- 14723577
TI  - Requirements for quantitative analysis of intimal reaction in arteries treated
      with intraluminal stents.
AB  - PURPOSE: To assess the reliability of quantitative histomorphometry measurements
      for the intimal reaction that occurs after intraluminal stenting in an animal
      model. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L
      lactic acid (PLA) stent and a stainless steel Wallstent, were implanted in the
      common iliac arteries of a beagle dog. After 45 days, the histomorphometry of the
      stented iliac artery segments was quantitatively measured. The relative standard
      error (RSE) of the estimate was calculated, and the reliability of measurements
      for maximal (LDmax) and minimal (LDmin) luminal diameters and internal (IELT) and
      external (EELT) elastic lamina thicknesses was assessed. RESULTS: The PLA stent
      required more measurements of variables from a single slide to ensure reliable
      (RSE<10%) results (1 for LDmax, 1 for LDmin, 8 for IELT, and 4 for EELT) compared
      to the Wallstent (1 for LDmax, 1 for LDmin, 2 for IELT, and 2 for EELT 2). The
      measured results were reliable for both stent materials when variables were
      measured from 2 slides of each segment (proximal/central/distal) of the stent.
      CONCLUSIONS: We conclude that these preliminary measurements to estimate the
      reliability of quantitative histomorphometry measurements should be made and
      reported before final results are given.

PMID- 14723578
TI  - Improvement in proximal aortic endograft fixation: an experimental study using
      different stent-grafts in human cadaveric aortas.
AB  - PURPOSE: To compare the proximal fixation characteristics of different types of
      stent-grafts (SG) and the adjunctive effect of a proximally placed Palmaz stent.
      METHODS: Human cadaveric aortas were obtained at autopsy and cut into 30 aortic
      segments. Appropriately oversized (10% to 20%) commercial stent-grafts (Zenith,
      Ancure, Excluder, Talent) and 4 configurations of homemade Palmaz-based stent
      grafts (polytetrafluoroethylene or polyester coverings each with no uncovered
      proximal edge or a 20-mm bare section of stent) were implanted 20 mm into an
      aortic segment and balloon dilated. Each segment was placed in an experimental
      apparatus to measure the dislodgment force. Bare Palmaz stents were used to
      reinforce the proximal fixation of the commercial stent-grafts, and the
      measurements were repeated. Manual anastomoses were made and their dislodgment
      force tested for comparison. RESULTS: The median dislodgment force ranged from
      6.5 N for the Excluder to 26.5 N for the Zenith (8.0 N for the Talent, 11.8 N for
      the Ancure, and 8.1 to 10.7 N for the various Palmaz stent-graft designs). There
      was no significant difference between the Zenith and the Ancure groups or between
      the Excluder and the Talent groups. However, the Zenith and Ancure devices
      required significantly higher (p=0.0004) force (approximately 25%) to displace
      them than the other stent-grafts tested. With the Palmaz stent added to the
      proximal attachment site, the median dislodgment force for the different
      commercial endografts was significantly improved for all devices (p<0.03): 34%
      for the Zenith device, 69% for the Ancure, 73% for the Talent, and 80% for the
      Excluder endoprosthesis. CONCLUSIONS: The Zenith stent-graft had the best
      resistance to dislodgment. An additional Palmaz stent placed at the proximal
      attachment site greatly improves endograft fixation regardless of the type of
      stent-graft. For complex aneurysm necks or for intraoperative type I endoleak
      management, an adjunctive Palmaz stent could be used.

PMID- 14723579
TI  - Non-axisymmetrical (life-like) abdominal aortic aneurysm models: a do-it-yourself
      approach.
AB  - PURPOSE: To construct life-like non-axisymmetrical abdominal aortic aneurysm
      models from latex. TECHNIQUE: A computed tomographic 3-dimensional reconstruction
      of an actual abdominal aortic aneurysm was cast in plastic to provide a core for
      a "chemical metal" mould. The mould was then coated with nonadhesive
      prevulcanized dipping latex and cured to provide an idealized hollow
      reconstruction of the aneurysm. CONCLUSIONS: Chemical metal can be manipulated
      quite easily to make a mould of any required size or surface character, which
      then allows the manufacture of a well-matched latex model for biophysical studies
      of non-axisymmetrical abdominal aortic aneurysms.

PMID- 14723580
TI  - Endotension is influenced by aneurysm volume: experimental findings.
AB  - PURPOSE: To investigate in an in vitro model whether and to what extent pressure
      is influenced by aneurysm size. METHODS: Latex aneurysms of 3 different volumes
      (24, 30, and 81 mL) were inserted into an in vitro circulation model. The
      systemic mean pressure (SP(mean)) was varied from 50 to 120 mmHg. The aneurysms
      were excluded using a woven polyethylene graft. Aneurysm sac mean pressure
      (ASP(mean)) was measured. RESULTS: In the in vitro model, endovascular aneurysm
      repair created a closed chamber without endoleak but showed a relevant aneurysm
      sac pressure. At an SP(mean) of 80 mmHg, the ASP(mean) was 42.0+/-0.6 mmHg in the
      24-mL aneurysm, 40.5+/-0.5 mmHg in the 30-mL model, and 19.3+/-0.5 mmHg in the 81
      mL aneurysm (p<0.05). The ASP(mean) rose with increasing SP(mean) and was
      inversely dependent on the aneurysm volume. CONCLUSIONS: This in vitro model
      demonstrated that the sac mean pressure correlated to the systemic pressure and
      that a greater aneurysm volume reduced aneurysm sac pressure. These data
      highlight the need for further studies regarding endotension.

PMID- 14723581
TI  - Doing better with cancer in adolescents and young adults.
AB  - Adolescents and young adults fare worse than children, yet do not have the same
      access to clinical trial therapy.

PMID- 14723582
TI  - Metformin and serious adverse effects.
AB  - Attention to known contraindications and intercurrent illness can avoid life
      threatening acidosis.

PMID- 14723583
TI  - Radiotherapy in Australia one year after the Baume report: vision or mirage?
AB  - Radiotherapy should be an integral part of a comprehensive national cancer
      control plan.

PMID- 14723584
TI  - Quality, morale and the new contract with GPs.

PMID- 14723585
TI  - Cancer in adolescents and young adults: treatment and outcome in Victoria.
AB  - OBJECTIVES: To describe the location of treatment, recruitment to clinical trials
      and outcomes for adolescents and young adults treated for cancer in Victoria.
      DESIGN AND SETTING: Retrospective review of all adolescents and young adults aged
      10-24 years diagnosed with cancer between 1992 and 1996, identified from the
      Victorian Cancer Registry. MAIN OUTCOME MEASURES: Treatment regimen (clinical
      trial, treatment protocol or neither), compliance with treatment and 5-year
      survival. RESULTS: Questionnaires were completed for 576 of 665 eligible
      adolescents and young adults (87% response rate). Recruitment into clinical
      trials decreased with increasing age. Adolescents aged 10-19 years were more
      likely to be recruited to a clinical trial if treated at a paediatric hospital.
      For all cancers, 5-year survival was similar across the age groups and was not
      influenced by the place of treatment. Only 1% of adolescents and young adults
      failed to complete planned therapy due to non-compliance. CONCLUSIONS: Despite a
      similar incidence of cancer to that in younger children, adolescents and young
      adults with cancer are poorly recruited into clinical trials in Victoria.
      Establishment of a cancer resource network in Victoria may provide information to
      both paediatric and adult oncologists about currently available clinical trials.

PMID- 14723586
TI  - Natural justice and human research ethics committees: an Australia-wide survey.
AB  - OBJECTIVE: To determine how familiar human research ethics committees (HRECs) are
      with the principles of natural justice and whether they apply these principles.
      DESIGN AND SETTING: A postal survey conducted between April and September 2002 of
      the Chairs of all HRECs registered with the Australian Health Ethics Committee of
      the National Health and Medical Research Council (NHMRC) in 2001. MAIN OUTCOME
      MEASURES: HRECs' reported familiarity with, and application of, three principles
      of natural justice: (1). the hearing rule, requiring a decision maker to allow a
      person affected by a decision to present his or her case; (2). the rule against
      bias, requiring a decision maker to be unbiased in the matter to be decided; and
      (3). the evidence rule, requiring that a decision be based on the evidence
      provided, and not irrelevant issues. RESULTS: From 201 Chairs of HRECs Australia
      wide, we received 110 completed questionnaires (55% response rate). About 33% of
      respondents were very familiar with the principles of natural justice, and 25%
      completely unfamiliar. Most respondents felt that natural justice should be, and
      usually is, applied by HRECs. In cases of possible positive bias of an HREC
      member towards a research proposal, 70% of respondents said they would exclude
      the member from decision making. In cases of possible negative bias, 43% said
      they would exclude the HREC member. CONCLUSION: The degree of familiarity with
      principles of natural justice varies widely among Chairs of HRECs. While many
      respondents felt that HRECs usually apply natural justice, responses to questions
      about bias suggest that HRECs do not always exclude members with possible bias,
      contrary to NHMRC guidelines.

PMID- 14723587
TI  - Access block in NSW hospitals, 1999-2001: does the definition matter?
AB  - OBJECTIVES: To estimate the magnitude of access block and its trend over time in
      New South Wales hospitals, using different definitions of access block, and to
      explore its association with clinical and non-clinical factors. DESIGN AND
      SETTING: An epidemiological study using the Emergency Department Information
      System datasets (1 January 1999 to 31 December 2001) from a sample of 55 NSW
      hospitals. MAIN OUTCOME MEASURES: Prevalence of access block measured by four
      different definitions; strength of association between access block, type of
      hospital, year of presentation, mode and time of arrival, triage category (an
      indicator of urgency), age and sex. RESULTS: Rates of access block (for all four
      definitions) increased between 1999 and 2001 by 1%-2% per year. There were
      increases across all regions of NSW, but urban regions in particular. Patients
      presenting to Principal Referral hospitals and those who arrived at night were
      more likely to experience access block. After adjusting for triage category and
      year of presentation, the mode of arrival, time of arrival, type of hospital, age
      and sex were significantly associated with access block. CONCLUSIONS: Access
      block continues to increase across NSW, whatever the definition used. We
      recommend that hospitals in NSW and Australia move to the use of one standard
      definition of access block, as our study suggests there is no significant
      additional information emerging from the use of multiple definitions.

PMID- 14723588
TI  - Olympic medals or long life: what's the bottom line?
AB  - On a per capita basis, Australia spent more than seven times as much on its
      Sydney Olympic team as did Canada, to win four times as many medals. Compared
      with Australia, Canada spent an additional amount per capita (standardised to the
      purchasing power parity rate at year 2000) of US dollars 1605 per life-year
      gained on healthcare in 2000. Neither country is "right" or "wrong" in making
      these funding choices, but they highlight the need for more explicit discussion
      about what is being spent, what is obtained for the given expenditure and what
      society actually values.

PMID- 14723589
TI  - Allgrove syndrome: when a recognisable paediatric disorder occurs in adulthood.
AB  - We report a man with longstanding undiagnosed adrenal insufficiency. At 37, our
      patient is the oldest reported case. Although most cases of Allgrove syndrome are
      diagnosed during childhood, awareness of this condition when undiagnosed in
      adults is crucial, as it is life threatening, and can severely affect
      neurological, sexual and psychological function.

PMID- 14723590
TI  - Whose health service is it anyway? Community values in healthcare.
AB  - There is growing interest in involving the public in decisions about healthcare
      provision. Citizens' juries, whose members were randomly selected from the
      electoral roll (rather than derived from consumer interest groups), have been
      trialled in Western Australia. When asked to take a community focus, presented
      with balanced evidence and given time to discuss and deliberate, the juries were
      able to identify and debate issues of broad principle, such as equity. Such
      issues seem to be best handled by referring to community values. Any public
      consultation process should provide sufficient information, opportunity for
      reflection and deliberation, and recognition of the scarcity of resources.

PMID- 14723591
TI  - Management of chronic low back pain.
AB  - Treatment for chronic low back pain (pain persisting for over 3 months) falls
      into three broad categories: monotherapies, mulitidisciplinary therapy, and
      reductionism. Most monotherapies either do not work or have limited efficacy (eg,
      analgesics, non-steroidal anti-inflammatory drugs, muscle relaxants,
      antidepressants, physiotherapy, manipulative therapy and surgery).
      Multidisciplinary therapy based on intensive exercises improves physical function
      and has modest effects on pain. The reductionist approach (pursuit of a
      pathoanatomical diagnosis with the view to target-specific treatment) should be
      implemented when a specific diagnosis is needed. While conventional
      investigations do not reveal the cause of pain, joint blocks and discography can
      identify zygapophysial joint pain (in 15%-40%), sacroiliac joint pain (in about
      20%) and internal disc disruption (in over 40%). Zygapophysial joint pain can be
      relieved by radiofrequency neurotomy; techniques are emerging for treating
      sacroiliac joint pain and internal disc disruption.

PMID- 14723592
TI  - Long-acting sulfonylureas -- long-acting hypoglycaemia.

PMID- 14723593
TI  - Management of chronic suppurative otitis media.

PMID- 14723594
TI  - Overweight and obesity in Australia: an underestimate of the true prevalence?

PMID- 14723595
TI  - Aspirin for cardiovascular disease prevention.

PMID- 14723596
TI  - The impact of chronic illness: partnerships with other healthcare professionals.

PMID- 14723597
TI  - Obstacles to research in complementary and alternative medicine.

PMID- 14723598
TI  - The regulation of complementary health: sacrificing integrity?

PMID- 14723599
TI  - Suppression of integrin activation by the membrane-distal sequence of the
      integrin alphaIIb cytoplasmic tail.
AB  - Integrin cytoplasmic tails regulate integrin activation including an increase in
      integrin affinity for ligands. Although there is ample evidence that the membrane
      proximal regions of the alpha and beta tails interact with each other to maintain
      integrins in a low-affinity state, little is known about the role of the membrane
      distal region of the alpha tail in regulation of integrin activation. We report a
      critical sequence for regulation of integrin activation in the membrane-distal
      region of the alphaIIb tail. Alanine substitution of the RPP residues in the
      alphaIIb tail rendered alphaIIbbeta3 constitutively active in a metabolic energy
      dependent manner. Although an alphaIIb/alpha6Abeta3 chimaeric integrin, in which
      the alphaIIb tail was replaced by the alpha6A tail, was in an energy-dependent
      active state to bind soluble ligands, introduction of the RPP sequence into the
      alpha6A tail inhibited binding of an activation-dependent antibody PAC1. In
      alphaIIb/alpha6Abeta3, deleting the TSDA sequence from the alpha6A tail or single
      amino acid substitutions of the TSDA residues inhibited alphaIIb/alpha6Abeta3
      activation and replacing the membrane-distal region of the alphaIIb tail with
      TSDA rendered alphaIIbbeta3 active, suggesting a stimulatory role of TSDA in
      energy-dependent integrin activation. However, adding TSDA to the alphaIIb tail
      containing the RPP sequence of the membrane-distal region failed to activate
      alphaIIbbeta3. These results suggest that the RPP sequence after the GFFKR motif
      of the alphaIIb tail suppresses energy-dependent alphaIIbbeta3 activation. These
      findings provide a molecular basis for the regulation of energy-dependent
      integrin activation by alpha subunit tails.

PMID- 14723601
TI  - Generation of polyclonal antibodies against multiple proteins in a single rabbit
      and subsequent isolation of the specific immunoglobulins as a tool for proteomics
      research.
AB  - A single rabbit has been immunized with a mixture of six different proteins:
      green fluorescent protein, ferredoxin:NADP oxidoreductase, NADPH:thioredoxin
      reductase, thioredoxin f, fructose bisphosphatase and cyclophilin. Individual
      IgGs were re-purified from the serum through specific interaction on small
      columns generated by grafting the antigen on a CNBr-Sepharose matrix. The
      specificity of the isolated IgG was checked by Western-blot analysis. Purified
      and specific IgG fractions were obtained with all antigens except thioredoxin f.

PMID- 14723600
TI  - Purification and biochemical characterization of the D6 chemokine receptor.
AB  - There is much interest in chemokine receptors as therapeutic targets in diseases
      such as AIDS, autoimmune and inflammatory disorders, and cancer. Hampering such
      studies is the lack of accurate three-dimensional structural models of these
      molecules. The CC-chemokine receptor D6 is expressed at exceptionally high levels
      in heterologous transfectants. Here we report the purification and biochemical
      characterization of milligram quantities of D6 protein from relatively small
      cultures of transfected mammalian cells. Importantly, purified D6 retains full
      functional activity, shown by displaceable binding of 125I-labelled MIP-1beta
      (macrophage inflammatory protein-1beta) and by complete binding of the receptor
      to a MIP-1alpha affinity column. In addition, we show that D6 is decorated on the
      N-terminus by N-linked glycosylation. Mutational analysis reveals that this
      glycosylation is dispensable for ligand binding and high expression in
      transfected cells. Metabolic labelling has revealed the receptor to also be
      sulphated and phosphorylated. Phosphorylation is ligand independent and is not
      enhanced by ligand binding and internalization, suggesting similarities with the
      viral chemokine receptor homologue US28. Like US28, an analysis of the full
      cellular complement of D6 in transfected cells indicates that >80% is found
      associated with intracellular vesicular structures. This may account for the high
      quantities of D6 that can be synthesized in these cells. These unusual properties
      of D6, and the biochemical characterization described here, leads the way towards
      work aimed at generating the three-dimensional structure of this seven
      transmembrane-spanning receptor.

PMID- 14723602
TI  - Combined inhibition of angiotensin II and endothelin suppresses the brain
      natriuretic peptide response to developing heart failure.
AB  - Blockade of AngII (angiotensin II) and ET (endothelin)-1, established and
      potential therapeutic strategies respectively, for heart failure, may have an
      adverse effect on the cardiac secretion of the natriuretic peptides, hormones
      with actions beneficial in this disease. The present study investigates the roles
      of AngII and ET-1 in regulating the stretch-induced release of the natriuretic
      peptides during the development of heart failure. On seven separate days, eight
      sheep underwent incremental left ventricular pacing (155, 190 and 225 beats/min
      for 90 min each) with concurrent infusions of a vehicle control, AngII, ET-1,
      AngII+ET-1, losartan [AT1 (AngII type 1) receptor antagonist], bosentan
      (ET(A)/ET(B) receptor antagonist) or losartan+bosentan. Pacing-induced rises in
      LAP (left atrial pressure) were amplified by the simultaneous administration of
      separate AngII and ET-1, and attenuated following blockade of the peptides, with
      maximum effects observed during combined treatments. Although these changes in
      atrial pressure were paralleled by concomitant alterations in circulating levels
      of both ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide), the
      plasma natriuretic peptide/atrial pressure relationship tended to be augmented by
      AngII and ET-1 and diminished by their blockade. A significant difference was
      demonstrated between the enhanced plasma BNP response to increasing LAP during
      combined AngII+ET-1 administration and decreased response during
      losartan+bosentan treatment ( P <0.05). A similar, but non-significant, trend was
      evident for ANP. The present study indicates dual AngII/ET-1 blockade diminishes
      BNP (and to a lesser extent ANP) secretion in developing heart failure,
      suggesting that augmentation of the natriuretic peptide system during the
      combination of these therapies may be of benefit.

PMID- 14723603
TI  - Mycophenolate mofetil treatment following renal transplantation decreases GTP
      concentrations in mononuclear leucocytes.
AB  - MMF (mycophenolate mofetil) has been proven to provide an effective
      immunosuppression by non-competitive selective reversible inhibition of IMPDH
      (inosine monophosphate dehydrogenase), the enzyme playing a crucial role in GTP
      biosynthesis. However, the exact metabolic changes induced by inhibition of IMPDH
      in target cells of the immune system have been the subject of recent debate. The
      aim of the present study was to evaluate whether MMF treatment produced sustained
      changes in the guanosine nucleotide pool of MNLs (mononuclear leucocytes) in
      vivo. Sixty-two renal failure patients were divided into three groups: chronic
      renal failure patients undergoing haemodialysis (CRF-HD; n=20) and two groups of
      patients after renal transplantation, the first on AZA (azathioprine; TN-AZA;
      n=23) and the second treated with MMF (TN-MMF; n=19). In addition, MNLs from 25
      healthy subjects were analysed as controls. Anion-exchange HPLC was used to
      quantify purine and pyrimidine nucleotides in MNLs. We report a significant
      decrease in GTP and the total MNL guanine nucleotide pool in the TN-MMF group
      (P<0.05) compared with control, CRF-HD and TN-AZA groups, although no significant
      differences were found between any of the other groups. Adenine nucleotide
      concentrations in MNLs were decreased in the TN-AZA group, but not in the TN-MMF
      group compared with the CRF-HD group and controls. There were no differences in
      CTP concentrations, but UTP concentrations were decreased in the CRF-HD, TN-AZA
      and TN-MMF groups compared with controls. MMF caused a significant and sustained
      decrease in the guanine nucleotide pool in MNLs from renal transplant recipients.
      This decrease contrasts with the elevation in GTP reported in erythrocytes of MMF
      treated patients.

PMID- 14723604
TI  - Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase,
      causes a paradoxical elevation of GTP in erythrocytes of renal transplant
      patients.
AB  - The immunosuppressant MMF (mycophenolate mofetil) has increasingly replaced AZA
      (azathioprine) in renal transplantation. MMF is a prodrug of MPA (mycophenolic
      acid), which inhibits lymphocyte IMPDH (inosine monophosphate dehydrogenase),
      thereby drastically decreasing GTP concentrations essential to lymphocyte
      proliferation in vitro and in vivo. Erythrocyte GTP concentrations are commonly
      elevated in severe renal disease, but normalize following successful engraftment.
      Consequently, elevated GTP in renal transplant recipients might signal impending
      loss of immunosuppression and graft failure. In the present study, we compared
      erythrocyte nucleotides and plasma metabolites in two groups of 25 patients after
      renal transplantation, both receiving prednisolone and cyclosporin A, but one
      group receiving MMF and the other AZA. No patients had recent allograft biopsy
      evidence of rejection. Erythrocyte GTP concentrations at MMF commencement were
      50.4+/-23.4 micromol/l. An increase occurred during the first 3 months after
      transplant when MMF was used de novo, stabilizing at 146.7+/-62.9 micromol/l
      after 4 months. This was significantly higher (P=2.5 x 10(-6)) than erythrocyte
      GTP (40.4+/-15.9 micromol/l) in the AZA group, which was essentially unchanged
      from values immediately after successful transplantation. The effect of MMF on
      erythrocyte GTP levels was reversible, since GTP levels fell when MMF therapy was
      terminated. The results demonstrate paradoxically high GTP concentrations in
      erythrocytes of renal transplant patients receiving MMF. MPA may stabilize
      reticulocyte IMPDH, allowing the protein to persist during erythropoiesis. This
      behaviour is in marked contrast with the decrease in GTP levels seen in white
      blood cells of patients on chronic MMF therapy.

PMID- 14723606
TI  - Review article: registered nurse-administered propofol sedation for endoscopy.
AB  - Propofol has several attractive properties that render it a potential alternative
      sedative agent for endoscopy. Compared with meperidine and midazolam, it has an
      ultra-short onset of action, short plasma half-life, short time to achieve
      sedation, faster time to recovery and discharge, and results in higher patient
      satisfaction. Shorter times to achieve sedation enhance efficiency in the
      endoscopy unit. Multiple studies have documented the safe administration of
      propofol by non-anaesthesiologists. Administration by registered nurses is more
      cost-effective than administration by anaesthesiologists. However, the
      administration of propofol by a registered nurse supervised only by the
      endoscopist is controversial because the drug has the potential to produce sudden
      and severe respiratory depression. More information is needed on how training
      nurses and endoscopists should proceed to give propofol, as well as the optimal
      level of monitoring to ensure the safety of nurse-administered propofol.

PMID- 14723607
TI  - Review article: diagnosis and current therapy of Wilson's disease.
AB  - Wilson's disease is an autosomal recessive inherited disorder of hepatic copper
      metabolism resulting in liver disease and/or neuropsychiatric disease. The
      diagnosis of neurological disease is straightforward if the following symptoms
      are present: Kayser-Fleischer rings, typical neurological symptoms and low serum
      ceruloplasmin levels. The diagnosis is more complex in patients presenting with
      liver diseases. None of the commonly used parameters alone allows a diagnosis
      with certainty. A combination of various laboratory parameters is necessary to
      firmly establish the diagnosis. In the future, limited mutation analysis may play
      an important diagnostic role. Recently, a group of international experts has
      proposed a score based on a variety of tests and clinical symptoms. The validity
      of this score needs to be assessed prospectively. Treatment requires life-long
      administration of copper chelators (d-penicillamine, trientine). A frequently
      used alternative is zinc. None of these treatments has been tested by prospective
      randomized controlled studies. Liver transplantation is reserved for severe or
      treatment-resistant cases with advanced liver disease, whilst experience with
      refractory neuropsychiatric disease is limited.

PMID- 14723605
TI  - Mechanisms of the interaction of nitroxyl with mitochondria.
AB  - It is now thought that NO* (nitric oxide) and its redox congeners may play a role
      in the physiological regulation of mitochondrial function. The inhibition of
      cytochrome c oxidase by NO* is characterized as being reversible and oxygen
      dependent. In contrast, peroxynitrite, the product of the reaction of NO* with
      superoxide, irreversibly inhibits several of the respiratory complexes. However,
      little is known about the effects of HNO (nitroxyl) on mitochondrial function.
      This is especially important, since HNO has been shown to be more cytotoxic than
      NO*, may potentially be generated in vivo, and elicits biological responses with
      some of the characteristics of NO and peroxynitrite. In the present study, we
      present evidence that isolated mitochondria, in the absence or presence of
      substrate, convert HNO into NO* by a process that is dependent on mitochondrial
      concentration as well as the concentration of the HNO donor Angeli's salt. In
      addition, HNO is able to inhibit mitochondrial respiration through the inhibition
      of complexes I and II, most probably via modification of specific cysteine
      residues in the proteins. Using a proteomics approach, extensive modification of
      mitochondrial protein thiols was demonstrated. From these data it is evident that
      HNO interacts with mitochondria through mechanisms distinct from those of either
      NO* or peroxynitrite, including the generation of NO*, the modification of thiols
      and the inhibition of complexes I and II.

PMID- 14723608
TI  - Review article: helminths as therapeutic agents for inflammatory bowel disease.
AB  - Over the last decade major advances have been made in our understanding of the
      mechanisms and mediators of inflammation that hold the promise of the development
      of new therapies for inflammatory disease. While much is to be gleaned from the
      application of new technologies, assessment of the age-old host-parasite
      relationship may also provide insights on how to counter pathological
      inflammatory events. In the case of inflammatory bowel disease [particularly
      Crohn's disease, which is associated with T helper 1 (Th1) events] it is proposed
      that infection with parasitic helminths would be beneficial: the paradigm being
      that of immune deviation, where Th2 cytokines mobilized in response to the
      helminth will prevent or antagonize the disease-promoting Th1 events in the gut.
      The situation is unlikely to be this simple. Here we review and critique the data
      in support of helminth therapy for inflammatory bowel disease, drawing attention
      to the gaps in knowledge and presenting a view on how the field may be advanced.
      While the concept of helminth therapy may be superficially unappealing, this
      review may convince the reader of the value of more extensive analyses of the
      impact of helminth infection on enteric inflammation.

PMID- 14723609
TI  - Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in
      the treatment of ulcerative colitis.
AB  - AIM: To determine whether there is a difference in short-term adverse events in
      patients with ulcerative colitis treated with mesalazine, olsalazine or
      balsalazide. METHODS: MEDLINE was searched for articles published until 2002.
      Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment
      of active disease or the maintenance of remission were included. Outcomes of
      interest were the frequencies of patients experiencing adverse events and those
      withdrawn due to adverse events. RESULTS: Forty-six trials were included. One
      study of mesalazine vs. sulfasalazine for active colitis showed significantly
      fewer patients with adverse events with mesalazine. Both balsalazide vs.
      sulfasalazine studies for active disease showed significantly fewer withdrawals
      with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance
      showed significantly fewer patients with adverse events with balsalazide.
      Otherwise, no significant differences in safety outcomes were noted. CONCLUSION:
      All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine
      treated patients, the frequencies of adverse events or withdrawals due to adverse
      events were comparable with those in placebo-treated patients and lower than
      those in sulfasalazine-treated patients. Overall, adverse events or withdrawals
      were not significantly more frequent with olsalazine than with placebo or
      sulfasalazine. Adverse events and study withdrawals on balsalazide were less
      frequent than those on sulfasalazine.

PMID- 14723610
TI  - Prersonal view: going around in circles -- circuitous medical management plans.
AB  - Physicians occasionally embark on a work-up that, after a lengthy path, leads
      them to a clinical situation similar to that from which they started their
      original pursuit. This article aims to describe the characteristics of circular
      medical management and means for its avoidance. The underlying medical problem
      often presents itself initially as a bewildering array of consecutive outcomes
      similar to a complex decision tree. On closer inspection, however, few of the
      outcomes are associated with a high probability, and only one path stands out as
      the most likely one to take. This path usually ends in such options as expectant
      management, supportive measures or doing nothing, which are already available at
      the onset of work-up. If medical management is drawn out and takes a long time to
      complete, sight of its circular nature is easily lost. If many different
      specialists care for a patient, little appreciation for circular paths occurs. A
      prospective outline of the management plan and the elimination of paths with low
      a priori probability can help to prevent unnecessary medical interventions. The
      physician may then come to realize that standing still and waiting become as
      effective and less costly than a lengthy circular work-up.

PMID- 14723611
TI  - Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs,
      cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients
      requiring chronic anti-inflammatory therapy.
AB  - AIM: To rationalize decision making around the use of different non-steroidal
      anti-inflammatory drug (NSAID) treatment strategies in patients with varying
      degrees of gastrointestinal and cardiovascular risk. METHODS: The panel comprised
      nine physicians (three rheumatologists, two internists, two gastroenterologists
      and two cardiologists) from geographically diverse areas practising in community
      based settings (n = 4) and academic institutions (n = 5). A literature review was
      performed by the authors on the risks, benefits and costs of NSAIDs, cyclo
      oxygenase-2-specific inhibitors and proton pump inhibitor co-therapy. The
      RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as
      'appropriate', 'uncertain' or 'inappropriate'. RESULTS: In patients with no
      previous gastrointestinal event and not concurrently on aspirin (low risk), the
      panel rated the use of an NSAID alone as 'appropriate' for those aged < 65 years,
      and the use of an NSAID +proton pump inhibitor or cyclo-oxygenase-2-specific
      inhibitor + proton pump inhibitor as 'inappropriate'. For patients aged > 65
      years and at low risk, an NSAID or cyclo-oxygenase-2-specific inhibitor alone was
      rated as 'uncertain'. For patients with a previous gastrointestinal event or who
      concurrently received aspirin, an NSAID alone was rated as 'inappropriate', and
      either a cyclo-oxygenase-2-specific inhibitor or an NSAID +proton pump inhibitor
      was rated as 'appropriate'. Finally, for patients with a previous
      gastrointestinal event and on aspirin, an NSAID or cyclo-oxygenase-2-specific
      inhibitor in conjunction with a proton pump inhibitor was rated as 'appropriate'.
      CONCLUSIONS: Clinicians and managed care entities need to balance the risks,
      benefits and costs of NSAIDs, cyclo-oxygenase-2-specific inhibitors and the
      prophylactic use of proton pump inhibitors. The guidelines given here can assist
      this process.

PMID- 14723612
TI  - Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the
      liver in children and adolescents.
AB  - BACKGROUND: Conventional treatment for autoimmune hepatitis results in a
      significant percentage of failures and several, poorly tolerated, side-effects.
      Therapy for autoimmune cholangitis and giant cell hepatitis associated with
      autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment
      for all of these diseases. METHODS: We reviewed the records of 12 patients
      treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two
      had autoimmune cholangitis and two had giant cell hepatitis. Indications for
      ciclosporin were treatment failure (four patients) and contraindications
      to/refusal of steroids (eight patients). Ciclosporin was administered in five
      untreated cases and in seven patients during relapse. The mean duration of
      ciclosporin administration was 35.6 months (8-89 months). The median follow-up
      was 6.5 years (1.5-15 years). RESULTS: All patients achieved complete remission
      in a median period of 4.5 weeks (2-12 weeks). No treatment withdrawal due to side
      effects occurred. Three patients required a combination of ciclosporin with
      conventional treatment due to severe liver function impairment. Tolerance to
      ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred
      in one case, gingival hypertrophy in two and moderate hypertrichosis in two.
      CONCLUSIONS: Ciclosporin may be considered as a safe treatment for all autoimmune
      liver diseases and as an effective alternative for front-line therapy.

PMID- 14723613
TI  - Dyspeptic symptoms associated with Helicobacter pylori infection are influenced
      by strain and host specific factors.
AB  - BACKGROUND: Dyspepsia can be associated with H. pylori infection. AIM: To assess
      dyspeptic symptoms and potentially influencing factors before and up to 6 months
      following successful H. pylori eradication therapy. METHODS: Prospective cohort
      study involving H. pylori positive subjects from ambulatory or hospitalized care.
      Main outcome measures were symptoms during baseline and follow-up, the proportion
      of symptom-free patients, and symptom scores. RESULTS: After successful
      eradication, the summary score of all dyspeptic symptoms decreased and during
      follow-up, the proportion of symptom-free patients was higher in the group with
      peptic ulcers (69.4% vs. 40.9%, P < 0.0001) than with functional dyspepsia (FD).
      Regardless of diagnosis, virulent strains of H. pylori were associated with a
      higher prevalence of epigastric pain before treatment: absolute risk-difference
      (ARD) with Oip-A: 18.2%, Odds Ratio (OR) 2.35 [1.3-4.2, 95%-CI], P = 0.01; with
      Cag-A: 24.6%, OR 2.81 [1.6-5], P = 0.01. Low-dose aspirin in part was a major
      risk factor in FD for previous weight loss bdfore study entry. Post-treatment,
      non-ulcer patients were more likely to suffer from distention/bloating. Likewise,
      alcohol induced persistence of nausea and vomiting in this population.
      CONCLUSIONS: Dyspeptic symptoms in H. pylori infected patients are more common
      with virulent strains. Symptoms are more likely to persist despite successful
      eradication if patients initially harboured virulent strains or concomitant
      aspirin or alcohol intake are present. In one-third of peptic ulcer patients,
      symptoms will not be cured 3 months after therapy.

PMID- 14723614
TI  - Impact of functional gastrointestinal disorders on health-related quality of
      life: a population-based case-control study.
AB  - BACKGROUND: The health-related quality of life is impaired in patients with
      functional gastrointestinal disorders seen in referral centres. AIM: To determine
      whether the health-related quality of life is impaired in subjects with
      functional disorders in the community and whether any differences can be
      explained by psychological co-morbidity. METHODS: In a population-based, nested,
      case-control study, subjects reporting symptoms of either dyspepsia or irritable
      bowel syndrome and healthy controls were interviewed and completed a battery of
      psychological measures plus a validated, generic, health-related quality of life
      measure (Medical Outcomes Study 36-item short form health survey, SF-36). The
      association between irritable bowel syndrome and dyspepsia and the physical and
      mental composite scores of SF-36 were assessed with and without adjustment for
      psychological state. RESULTS: One hundred and twelve cases (30 dyspepsia, 39
      irritable bowel syndrome, 32 dyspepsia and irritable bowel syndrome and 11
      gastrointestinal symptoms but not dyspepsia or irritable bowel syndrome) and 110
      controls were enrolled. In the unadjusted linear regression models, irritable
      bowel syndrome (but not dyspepsia) was negatively associated with the physical
      composite score (P < 0.05); in an adjusted model, the association between the
      physical health-related quality of life and irritable bowel syndrome was
      explained by the Symptom Checklist-90 somatization score alone. In unadjusted
      models, irritable bowel syndrome and dyspepsia were each negatively associated
      with the mental composite score (P < 0.05). The association between the mental
      health-related quality of life and dyspepsia remained after adjusting for
      psychological covariates, but the association between this and irritable bowel
      syndrome was not significant after adjustment. CONCLUSIONS: In the community,
      health-related quality of life is impaired in subjects with irritable bowel
      syndrome and dyspepsia; however, much of this association can be explained by
      psychological factors.

PMID- 14723615
TI  - 13C-methacetin breath test for monitoring hepatic function in cirrhotic patients
      before and after liver transplantation.

PMID- 14723616
TI  - Influenza virus: immunity and vaccination strategies. Comparison of the immune
      response to inactivated and live, attenuated influenza vaccines.
AB  - Influenza virus is a globally important respiratory pathogen which causes a high
      degree of morbidity and mortality annually. The virus is continuously undergoing
      antigenic change and thus bypasses the host's acquired immunity to influenza.
      Despite the improvement in antiviral therapy during the last decade, vaccination
      is still the most effective method of prophylaxis. Vaccination induces a good
      degree of protection (60-90% efficacy) and is well tolerated by the recipient.
      For those at risk of complications from influenza, annual vaccination is
      recommended due to the antigenic changes in circulating strains. However, there
      is still room for improvement in vaccine efficacy, long-lasting effect, ease of
      administration and compliance rates. The mucosal tissues of the respiratory tract
      are the main portal entry of influenza, and the mucosal immune system provides
      the first line of defence against infection. Secretory immunoglobulin A (SIgA)
      and IgM are the major neutralizing antibodies directed against mucosal pathogens.
      These antibodies work to prevent pathogen entry and can function intracellularly
      to inhibit replication of virus. This review describes influenza virus infection,
      epidemiology, clinical presentation and immune system response, particularly as
      it pertains to mucosal immunity and vaccine use. Specifically, this review
      provides an update of the current status on influenza vaccination and
      concentrates on the two main types of influenza vaccines currently in use, namely
      the cold-adapted vaccine (CAV) given intranasally/orally, and the inactivated
      vaccine (IV) delivered subcutanously or intramuscularly. The commercially
      available trivalent IV (TIV) elicits good serum antibody responses but induces
      poorly mucosal IgA antibody and cell-mediated immunity. In contrast, the CAV may
      elicit a long-lasting, broader immune (humoral and cellular) response, which more
      closely resembles natural immunity. The immune response induced by these two
      vaccines will be compared in this review.

PMID- 14723617
TI  - Computer-assisted prediction of HLA-DR binding and experimental analysis for
      human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of
      Mycobacterium tuberculosis.
AB  - The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for
      Mycobacterium tuberculosis complex and M. leprae. The present study was carried
      out to identify the promiscuous T helper 1 (Th1)-cell epitopes of the M.
      tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic
      peptides (25 mers overlapping by 10 residues) covering the sequence of the
      complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of
      nine serologically defined HLA-DR molecules, by using a virtual matrix-based
      prediction program (propred), showed that eight of the 15 peptides of Rv2945c
      were predicted to bind promiscuously to >/=10 alleles from more than or equal to
      three serologically defined HLA-DR molecules. The Th1-cell reactivity of all the
      peptides was assessed in antigen-induced proliferation and interferon-gamma (IFN
      gamma)-secretion assays with peripheral blood mononuclear cells (PBMCs) from 37
      bacille Calmette-Guerin (BCG)-vaccinated healthy subjects. The results showed
      that 17 of the 37 donors, which represented an HLA-DR-heterogeneous group,
      responded to one or more peptides of Rv2945c in the Th1-cell assays. Although
      each peptide stimulated PBMCs from one or more donors in the above assays, the
      best positive responses (12/17 (71%) responders) were observed with the peptide
      p14 (aa 196-220). This suggested a highly promiscuous presentation of p14 to Th1
      cells. In addition, the sequence of p14 is completely identical among the LppX of
      M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of
      Rv2945c and p14 in the subunit vaccine design against both tuberculosis and
      leprosy.

PMID- 14723619
TI  - The four mouse IgG isotypes differ extensively in bactericidal and
      opsonophagocytic activity when reacting with the P1.16 epitope on the outer
      membrane PorA protein of Neisseria meningitidis.
AB  - Mouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for
      the P1.16 epitope on the meningcoccal PorA protein, were tested for functional
      activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme
      linked immunosorbent assay, showed similar values for all the MoAbs. The serum
      bactericidal activity (SBA) defined as the lowest concentration of antibodies
      giving 50% reduction in the number of meningococcal colony-forming units using
      human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1.
      For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1.
      OP was measured in flow cytometry using log-phase live meningococci as target
      cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector
      cells and human serum as a complement source. The mouse MoAbs were negative in OP
      when using human PMNs in the absence of complement. The results demonstrate the
      importance of choosing the right isotype of mouse MoAbs when using them to judge
      the potential vaccine importance of their corresponding antigen. If such MoAbs
      should be used for passive vaccination against infectious diseases, the isotype
      would presumably play an important role for their anticipated clinical effects.

PMID- 14723618
TI  - Changes in neutrophil surface-receptor expression after stimulation with FMLP,
      endotoxin, interleukin-8 and activated complement compared to degranulation.
AB  - Neutrophil activation induces changes in the expression of surface receptors and
      may lead to degranulation. Surface expression of beta2-integrins, l-selectin,
      complement receptor 1 (CR-1), decay-accelerating factor (DAF), C5a receptor,
      intercellular adhesion molecule-1 (ICAM-1) and ICAM-3 was compared by flow
      cytometry on isolated neutrophils stimulated with phorbol 12-myristate 13-acetate
      (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), endotoxin or interleukin-8
      and on neutrophils in whole blood anti-coagulated with the thrombin inhibitor
      lepirudin and stimulated with cobra venom factor to induce complement activation.
      Myeloperoxidase and lactoferrin in the supernatants were quantified in enzyme
      immunoassays. With high enough doses, all stimulants induced significant
      upregulation of beta2-integrins, CR-1 and DAF and downregulation of l-selectin.
      ICAM-3 was either unchanged or somewhat downregulated. Only FMLP and PMA induced
      significant upregulation of ICAM-1. Combined measurement of beta2-integrins and l
      selectin permitted graded evaluation of early neutrophil activation. Measurement
      of degranulation showed no differences compared to unstimulated controls due to
      substantial spontaneous degranulation of isolated neutrophils by rewarming from 4
      degrees C and incubation at 37 degrees C. Spontaneous activation was less in
      ethylenediaminetetraacetic acid-anti-coagulated blood, but calcium chelation may
      also inhibit the stimulated responses. There was large activation of unstimulated
      neutrophils in lepirudin-anti-coagulated blood at 37 degrees C, obscuring changes
      induced by stimulation, which may render this anti-coagulant unsuitable for
      studies of neutrophils.

PMID- 14723620
TI  - CD47 ligation induces a rapid caspase-independent apoptosis-like cell death in
      human monocytes and dendritic cells.
AB  - CD47 is a versatile cell-surface molecule expressed on nearly all haematopoietic
      cells. In its capacity as a thrombospondin-1 (TSP-1) receptor, CD47 has recently
      been shown to mediate cell death in certain cells, for example, activated but not
      resting T cells. Here, we have investigated the possibility that human monocytes
      and dendritic cells (DCs) undergo cell death, following CD47 ligation. Using the
      TSP-1-derived CD47-binding peptide 4N1K, we found that both freshly isolated
      monocytes and monocyte-derived DCs underwent a rapid, caspase-independent cell
      death. This was characterized by the simultaneous presence of phosphatidylserine
      exposure, plasma membrane permeability, reduced mitochondrial membrane potential
      and highly fragmented DNA. Not all cells were sensitive to 4N1K-induced
      apoptosis; a plateau of cell death reached at an average of 38% of the monocyte
      and DCs populations. The results presented here, thus, show that CD47 can mediate
      a rapid apoptosis-like cell death of human monocytes and DCs.

PMID- 14723621
TI  - Ligation of CD47 during monocyte differentiation into dendritic cells results in
      reduced capacity for interleukin-12 production.
AB  - We have previously shown that the CD47-binding thrombospondin-1 (TSP-1)-derived
      peptide 4N1K induces a rapid apoptosis-like death of human monocytes and
      dendritic cells (DCs). However, not all cells were susceptible to the peptide
      induced cell death and here, we have investigated whether surviving monocytes
      could differentiate into functionally normal DCs. We found that the cell-surface
      phenotype, the T-cell stimulatory capacity and the ability to undergo
      lipopolysaccharide (LPS)-induced maturation into CD83+ DCs were essentially
      identical in 4N1K-derived and control DCs. Interleukin-10 (IL-10) production was
      also normal, but a significant downregulation of the pro-inflammatory cytokines
      IL-12 and tumour necrosis factor-alpha (TNF-alpha) was observed in the 4N1K
      derived DCs. To the contrary, simultaneous stimulation of control DCs with 4N1K
      and LPS + interferon-gamma did not alter IL-12 production. These results indicate
      that although activation of the TSP-1-binding region of CD47 on monocytes induces
      apoptosis in a large proportion of the cells, it does not hamper the overall
      capacity of the surviving cells to differentiate into DCs. Such DCs, however,
      have a reduced capacity for IL-12 and TNF-alpha production, and the possibility
      that this is linked to the uptake of apoptotic cells is discussed.

PMID- 14723622
TI  - Synthesis and immunological activity of a branched peptide carrying the T-cell
      epitope of gp43, the major exocellular antigen of Paracoccidioides brasiliensis.
AB  - The 43 kDa glycoprotein (gp43) of Paracoccidioides brasiliensis is the major
      diagnostic antigen of paracoccidioidomycosis (PCM), a prevalent fungal infection
      in South America. A 15-mer sequence from gp43, denominated P10, induced T-CD4+ T
      helper 1 cellular immune responses in mice of three different haplotypes and
      protected against intratracheal challenge by a virulent isolate of P.
      brasiliensis. In an attempt to improve delivery of P10, a promiscuous antigen
      also presented by human leucocyte antigen-DR alleles, aiming at immunotherapy, we
      synthesized a multiple antigen peptide with the protective T-cell epitope
      expressed in a tetravalent 13-mer analog of P10 (M10). M10 induced specific lymph
      node cell proliferation in mice preimmunized with peptides in complete Freund's
      adjuvant (CFA). In addition, M10 immunization without CFA significantly protected
      intratracheally infected mice. We conclude that M10 is a candidate for an anti
      PCM vaccine. In this report we describe: (1) the synthesis of M10; (2) the
      induction of M10-elicited T-cell response and (3) in vivo protection of mice
      immunized with M10 and challenged by a virulent strain of P. brasiliensis.

PMID- 14723623
TI  - Immunological crossreactivity of the Mycobacterium leprae CFP-10 with its
      homologue in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis culture filtrate protein-10 (CFP-10) (Rv3874) is
      considered a promising antigen for the immunodiagnosis of tuberculosis (TB)
      together with early secreted antigens of M. tuberculosis (ESAT-6). Both ESAT-6
      and CFP-10 are encoded by the RD1 region that is deleted from all tested M. bovis
      bacille Calmette-Guerin (BCG) strains but present in M. leprae, M. tuberculosis,
      M. bovis, M. kansasii, M. africanum and M. marinum. In this study, the homologue
      of CFP-10 in M. leprae (ML0050) is identified and characterized. Interferon-gamma
      production in response to this homologue by T cells from leprosy patients, TB
      patients and unexposed controls shows that CFP-10 of M. leprae is a potent
      antigen that crossreacts with CFP-10 of M. tuberculosis at the T-cell level. This
      crossreactivity has implications for the use of CFP-10 of these mycobacterial
      species as diagnostic tool in areas endemic for both the diseases.

PMID- 14723624
TI  - Low number of H-2Dd-negative haematopoietic cells in mixed bone marrow chimeras
      convey in vivo tolerance to H-2Dd-negative cells but fail to prevent resistance
      to H-2Dd-negative leukaemia.
AB  - Natural killer (NK) cells kill cells lacking self major histocompatibility
      complex (MHC) class I. This missing self reactivity is beneficial in
      haploidentical bone marrow transplantations to cure leukaemia, in which donor
      derived NK cells reject MHC disparate leukaemia cells and prevent relapse. To
      understand the role of NK cells in transplantation, we have studied NK cell
      tolerance in mice receiving mixed bone marrow transplants with limiting number of
      the MHC disparate component. Using an MHC class I (Dd) transgenic mouse model, we
      generated bone marrow chimeras carrying mixtures of Dd-positive and -negative
      cells. NK reactivity against Dd-negative cells (missing self) was assayed by
      outgrowth of lymphoma cells, stability of the chimerism in vivo and killing of
      Concanavalin A blasts in vitro. Up to 20% Dd-negative haematopoietic cells
      reduced, but did not abrogate, rejection of Dd-negative tumours and killing of Dd
      negative T-cell blasts. In contrast, the ratios between Dd-positive and -negative
      cells were stable in vivo, suggesting tolerance to normal cells. Our data suggest
      that NK cell tolerance to normal cells and tumours in mixed MHC environments is
      differentially regulated, tolerance to normal cells being more easily induced.
      These results are important in relation to the role of NK cells in antileukaemic
      reactions after bone marrow transplantation.

PMID- 14723625
TI  - Clinical association of anti-golgi autoantibodies and their autoantigens.
AB  - Anti-Golgi autoantibodies (AGAs) and their targets have been reported from
      several diseases. However, the association of AGAs, selective autoantigens and
      related clinical diseases is still obscure. In this study, the presence of AGAs
      in the sera of 5983 patients was screened to explore the association of AGAs and
      clinical diseases. By means of indirect immunofluorescence using HEp-2 cells,
      sera of 12 patients bearing AGAs were identified. The location of recognized
      Golgi autoantigen(s) was confirmed by the treatment of monensin and double
      immunostaining using beta-COP. Using the immunoelectron microscopy, AGA
      immunoreactivity was clearly demonstrated at a stack structure, characteristic of
      the Golgi complex. Furthermore, analysis of the 12 AGA-positive sera by Western
      blot revealed at least 15 components of Golgi antigens with relative molecular
      weights ranging from 54 to 350 kDa, and several Golgi autoantigens identified may
      be novel. Notably, over half of the AGA-positive cases found belong to non
      autoimmune diseases, particularly hepatic disorder. This study presents the
      association of AGAs, components of the Golgi complex and clinical diseases.

PMID- 14723626
TI  - Effect of dendritic cells on flow cytometric quantification of cytomegalovirus
      specific, interferon-gamma-producing T cells.
AB  - Flow cytometric measurement of intracellular cytokines in T cells exposed to
      antigen is a widely used method for quantification of an antigen-specific T-cell
      response. As the frequency of antigen-specific T cells is often very low, any
      improvement in signal to noise ratio is of great importance. Thus, in this study,
      the ability of antigen-pulsed dendritic cells (DCs) to increase the number of
      antigen-specific, interferon-gamma (IFN-gamma)-producing CD4+ T cells measurable
      both in fresh peripheral blood and in reconstituted frozen blood mononuclear cell
      (MNC) samples was evaluated. Cytomegalovirus (CMV) was used as antigen in a 10 h
      assay, using cells from both CMV-seropositive and -seronegative donors. When
      reconstituted frozen samples were analysed, the general response towards CMV
      lysate in CMV-seropositive donors was 23-86% lower compared to the corresponding
      fresh blood samples. Antigen-pulsed DCs could not improve the sensitivity of the
      intracellular cytokine-detection assay when fresh peripheral blood samples were
      used. Interestingly, however, the addition of CMV lysate-pulsed DCs to
      cryopreserved MNC samples substantially increased the frequency of specifically
      induced IFN-gamma-producing cells to a level comparable to the frequency found in
      the corresponding fresh blood samples.

PMID- 14723627
TI  - Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic
      study.
AB  - Mannose-binding lectin (MBL) is an important component of innate immunity that
      can bind to certain sugar residues on the surface of many types of pathogenic
      micro-organisms. On binding, MBL generates opsonic activity mainly through
      activation of the complement system. Genetically determined MBL deficiency is
      very common and can be associated with increased susceptibility to a variety of
      infections, especially in children and immunosuppressed individuals. The
      potential benefits of MBL reconstitution therapy therefore need to be evaluated.
      We have carried out a phase I safety and pharmacokinetic study on 20 MBL
      deficient healthy adult volunteers. The MBL was prepared from plasma of
      nonremunerated, voluntary Danish donors tested and found negative for hepatitis B
      surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C
      virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given
      intravenously, once weekly over a period of 3 weeks. The volunteers were closely
      monitored at the University Hospital in Reykjavik for 8 h after each infusion and
      daily thereafter for 5 days after each infusion. No adverse clinical or
      laboratory changes were observed in any of the 20 participants, and frequent
      measurements did not reveal any signs of infusion-associated complement
      activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks
      after the last infusion. Serum MBL levels increased up to normal levels (1200
      4500 ng/ml) immediately after each infusion, but the half-life of the infused MBL
      was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that
      infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe.
      However, adults have to be given at least 6 mg twice or thrice weekly for
      maintaining protective MBL levels assumed to be about 1000 ng/ml.

PMID- 14723628
TI  - The effects of interferon-alpha2a on concentrations of immunoglobulins,
      complement and lymphocytes in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) patients treated with type I interferon experience
      reduced disease activity. Because immunoglobulins (Igs), complement and
      lymphocytes have been given a role in the pathogenesis of MS, we investigated the
      longitudinal effect of interferon-alpha2a (IFNA) on the variability of these
      parameters. Patients were treated for 6 months with 4.5 million international
      units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23
      patients). IFNA induced a significant increase in concentrations of total IgG and
      IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had
      increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no
      significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the
      effect on IgM was borderline significant. After 6 months, IgM had increased by
      0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant
      increase in the concentration of C1 inhibitor (INH). At 3 months, the mean
      concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months,
      C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The
      effect of IFNA on C4 was inconclusive but indicates an effect during the initial
      phase of the treatment. C3 showed no significant treatment-mediated change. IFNA
      induced a significant decrease in lymphocyte concentrations by 0.56 x 106
      lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant
      associations between changes in immune parameters and changes in clinical and
      magnetic resonance imaging scores. The results verify that IFNA modulates and
      activates both the innate and the adaptive arms of the immune system. The
      observations should be of relevance when evaluating mechanisms of action of IFN
      treatment in MS.

PMID- 14723629
TI  - Limited magnitude and breadth in the HLA-A2-restricted CD8 T-Cell response to Nef
      in children with vertically acquired HIV-1 infection.
AB  - CD8 T cells are believed to play a key role in the immune control of human
      immunodeficiency virus-1 (HIV-1) infection in children as well as in adults. We
      have used an enhanced EliSpot (AmpliSpot) assay to quantitate CD8 T-cell
      responses directed to five human leucocyte antigen (HLA)-A2-presented HIV-1
      epitopes derived from the key viral antigen Nef. Responses were assayed in one
      group of 21 children with vertically acquired HIV infection and one group of 19
      adult subjects with chronic infection. The paediatric group displayed
      significantly weaker and more narrowly focused CD8 T-cell responses as compared
      with the adult subjects. Two epitopes stood out as the most frequently and
      strongly recognized, suggesting that they should be considered immunodominant in
      the CD8 T-cell response to HIV-1 Nef. Interestingly, the most frequently and
      strongly recognized epitope in both adults and children was previously identified
      in HLA-A2-transgenic mice, demonstrating the usefulness of such mice in finding
      natural viral epitopes. These findings indicate significant weakness in strength
      and breadth of the CD8 T-cell response to the target protein Nef in infected
      children and prompt renewed efforts into the immunology of vertically acquired
      HIV-1 infection.

PMID- 14723632
TI  - Changing face of mental health nursing.

PMID- 14723633
TI  - Did anything change? Caregivers and schizophrenia after medication changes.
AB  - This paper reports on a qualitative, critical study into the lives of relatives
      and partners of people living with enduring effects of schizophrenia. A review of
      the literature showed that caregivers and relatives of sufferers were seldom
      asked about their experiences, instead they were subject to blame or criticism
      regarding their parental or caregiving practices. Caregivers of people with
      schizophrenia were interviewed in order to reveal their experience of caring for
      their kin after a medication change to atypical neuroleptics. The interview
      analysis was compared with mental health professional literature, using a
      Foucauldian approach to reveal the operation of language and power in the
      positioning of caregivers. This analysis was then compared to the talk of the
      caregivers. Similarities and differences in their ways of talking about caring
      were identified. Caregivers spoke of protracted periods of time before the
      establishment of a definite diagnosis, ambivalence about medication and 'never
      giving up'. The paper concludes that life for caregivers is constituted as doubly
      problematic, experiencing stigma personally and vicariously through their kin.

PMID- 14723634
TI  - Advancing self-determination with young adults who have schizophrenia.
AB  - The research examined how community mental health nurses promote self
      determination with clients who are experiencing an early episode of
      schizophrenia. The study used grounded theory methodology incorporating
      interviews and observations. The study took place in the community, in rural and
      regional New South Wales, Australia, and involved clients and community mental
      health nurses. The findings show that the promotion of self-determination is
      dependent on nurses educating clients about their illness and well-being, and
      fostering self-control. The development of a reciprocal relationship, or
      alliance, between nurses and clients is implicit in advancing self-determination.
      The implications of the promotion of client self-determination for education,
      clinical practice and research and these are discussed.

PMID- 14723635
TI  - The multidisciplinary approach to mental health crisis management: an Australian
      example.
AB  - Changes within the Australian health care system have led many people with mental
      health disorders to use emergency departments as the point of access to mental
      health services. Staff in emergency departments are not necessarily equipped to
      assess the needs of such clients. This paper briefly describes the development of
      a multidisciplinary mental health liaison team, within the emergency department
      of one hospital in Sydney, which was designed to assist both staff and clients.
      Available evidence suggests the implementation of the team has been a success,
      however, more research is required to confirm the effectiveness of this approach.
      Questions are raised about appropriate referral and follow-up for some clients.
      The study also found deficiencies in the method of routine data collection
      (Emergency Department Identification System), which makes formal auditing of the
      team and the services it provides a difficult task.

PMID- 14723636
TI  - 'Caught in the middle'? Mental nurse training in England 1919-51.
AB  - The early history of mental health nurse training is one that has only been
      partially researched. While some writers have discussed the content and impact of
      training on the development of mental health nursing, little has been written on
      the professional and institutional factors that influenced this development. The
      medical profession, psychiatry, was to play an important role in the development
      of training and regulation of nursing staff in the large Victorian asylums and
      was an important influence on the knowledge base of mental health nursing. Their
      professional organization, the Medico-Psychological Association (the Royal Medico
      Psychological Association after 1926 when they acquired a royal prefix) produced
      the first textbook for asylum nurses in 1885 and established a national training
      scheme for them 4 years later. However, in 1919 the Nurses Registration Act
      established the General Nursing Council for England and Wales and this body was
      given statutory responsibility for the training and registration of nurses,
      including 'mental' nurses. They were soon to be in conflict with the Medico
      Psychological Association. The two organizations continued to run their own rival
      training schemes for mental health nurses for over 30 years, the Royal Medico
      Psychological Association finally relinquishing their role in 1951. The Royal
      Medico-Psychological Association scheme proved far more popular than the General
      Nursing Councils, with significantly more nurses participating in it. This paper
      discusses these organizational influences on the development of 'mental nurse'
      training and discusses the possible impact that they have had on the knowledge
      base of mental health nursing.

PMID- 14723637
TI  - The perception of aggression by nurses: psychometric scale testing and derivation
      of a short instrument.
AB  - Patient aggression is a serious problem in psychiatric nursing. Nurses' attitudes
      towards aggression have been identified as mediating the choice of nursing
      interventions. To date, investigations are lacking which elucidate the stability
      of one of the few scales for measuring the attitude of aggression. This study
      aimed to investigate the test-retest stability of the Perception of Aggression
      Scale and to derive a shortened version. In order to test the reliability of the
      Perception of Aggression Scale items, three groups of psychiatric nurses were
      requested to fill in the Perception of Aggression Scale twice (30 student nurses
      after 4 days, 32 qualified nurses after 14 days and 36 qualified nurses after 70
      days). We derived the shortened version from an independent data set obtained
      from 729 psychiatry nurses using principal component analysis, aiming to maximize
      parsimony and Cronbach's alpha. Amongst competing short versions, we selected
      those with the highest reliability at 70 or 14 day retest. A scale using 12 of
      the original 32 items was derived yielding alphas of r = 0.69 and r = 0.67 for
      the two POAS factors with retest reliabilities of r = 0.76 and r = 0.77. The
      shortened scale offers a practical and viable alternative to the longer version.

PMID- 14723638
TI  - Stress, sources of stress and ways of coping among psychiatric nursing students.
AB  - This study measured levels of distress, sources of stress and ways of coping of a
      convenience sample of psychiatric nursing students (n = 35). Instruments used
      were the 30-item General Health Questionnaire, the Jones and Johnson (1997)
      Student Nurse Stress Index, Parkes (1985) Ways of Coping Questionnaire and a
      demographic questionnaire. Findings revealed that all students were significantly
      distressed, exceeding a conventional cut-off score of 5 on the 30-item General
      Health Questionnaire. Students were found to have limited coping skills.
      Preparing to become a nurse in this setting was found to be significantly
      emotionally stressful and a possible risk to the well-being of students. This
      study provides a baseline from which to address the problem of stress among
      diplomate psychiatric nursing students.

PMID- 14723639
TI  - Defining dual diagnosis of mental illness and substance misuse: some
      methodological issues.
AB  - This paper discusses methodological issues arising in the initial stages of a
      larger epidemiological case-control study. Practitioners from both Generic Mental
      Health and Substance Misuse Services (n = 170) were asked to identify which of
      their clients, from a time-limited caseload (n = 2341), had comorbid mental
      health and substance misuse problems. Although practitioners were provided with a
      definition of 'singly diagnosed' and 'dually diagnosed', it became apparent that
      these definitions were applied pragmatically, depending on the nature of the
      client's primary problem and the agency they were presenting to. Issues raised
      include the time period in which a client was considered to have a concurrent
      mental health problem and substance misuse, how a 'mental health problem' was
      defined and whether a personality disorder should be categorized as a 'mental
      health problem'. There was also some disagreement about whether clients who were
      being treated primarily by Substance Misuse Services, but were also taking
      prescribed antidepressants, implicitly had a 'mental health problem'. We raise
      these methodological issues, as they have implications for determining the
      prevalence of 'dual diagnosis' and the subsequent provision of services.

PMID- 14723640
TI  - Rejection--a neglected phenomenon in psychiatric nursing.
AB  - The basically asymmetric character of the 'psychotic patient-psychiatric nurse'
      relationship constitutes an ethical challenge for the nurse. One aspect of this
      relationship is that nurses must constantly self-consciously control their
      behaviour towards the patient. There is some evidence that the patient sometimes
      feels offended because of his perception that the nurse rejects him. The purpose
      of this article is to examine the role rejection plays in the 'psychotic patient
      psychiatric nurse' relationship and ethical implications this might have for the
      field of psychiatric nursing. This study is conducted using an ethnographic
      research design that includes participant observation and narrative interviews of
      nurses working on an acute ward of a psychiatric hospital. One case is analysed
      and discussed in depth through the philosophical insights (particularly 'the
      ethical demand') of the Danish moral philosopher K.E. Logstrup. The psychotic
      patient, being vulnerable, dependent, and trusting, confronts the psychiatric
      nurse with a constant 'ethical demand' to take care of him. The patient's trust,
      and his fight to maintain his dignity, creates a risk of being rejected. The
      nurse, by resorting to the tactic of 'impersonal professional routine', which
      does not define the relationship as a personal encounter, creates boundaries
      between herself and the patient. The nurse's withdrawal from the patient's
      perception of reality is experienced by the patient as rejection and hence an
      offence of his dignity. The nurse's rejection of the patient has two causes:
      external factors--for example inadequate staffing--cause the nurse to be unable
      to live up to the professional ideal of 'welcoming' the patient; internal factors
      -for example the profession's understanding of itself--create an unclear
      understanding of the nurse's role and responsibilities. It is necessary to work
      with both the external and internal factors to improve psychiatric nursing.

PMID- 14723641
TI  - Family intervention in routine practice: it is possible!
AB  - Family Intervention for individuals with schizophrenia has a wealth of evidence
      to attest its efficacy. However, there is little literature available about
      actual family work services, what they consist of and how they operate. With the
      publication of the National Institute for Clinical Excellence guidelines for
      schizophrenia in 2002, there is increased pressure on mental health services to
      deliver evidence-based Family Interventions to individuals with schizophrenia and
      their families. This article will outline how a specialist mental health Trust
      have been able to successfully establish and implement a designated Family
      Intervention service into routine practice.

PMID- 14723642
TI  - Nurse staffing levels and budgeted expenditure in acute mental health wards: a
      benchmarking study.
AB  - This paper describes benchmarking research undertaken within one former National
      Health Service Executive region examining acute ward funded and actual staffing
      establishments and funded expenditure for mental health nursing staff. Staffing
      establishment data were obtained for all 73 acute wards within the region. Of the
      established posts for trained mental health nurses across these wards, it was
      identified that there were 12% vacancies (117.99 whole time equivalent) at the
      time of the study. While some of the shortfall was dealt with by recruiting
      untrained nursing staff above funded establishments, there remained an overall
      shortfall in the total nursing workforce across the system of acute wards in the
      region. Although most of the provider trusts in the region were in development or
      experiencing major organizational change at the time of the study, considerable
      variation existed within and between trusts. Variations were identified in funded
      and actual nursing establishments and cost per bed, raising significant issues
      for trusts and their local mental health economies. Variations based on mixed-
      and single-sex wards were also noted. Findings are discussed in respect of the
      issues raised for the development of wards, provider trusts and their local
      systems. The utility of the methodology developed in this work is also discussed.

PMID- 14723643
TI  - The effects of a transitional discharge model for psychiatric patients.
AB  - This pilot randomized control trial was motivated by the discovery that many
      individuals with mental health problems are re-hospitalized within a year, with
      many being unable to fully adjust to community living. A solution was proposed in
      the form of an intervention called transitional discharge. The transitional
      discharge model included: (1) peer support, which is assistance from former
      patients who provide friendship, understanding and encouragement; and (2) overlap
      of inpatient and community staff in which the inpatient staff continue to work
      with the discharged patient until a working relationship is established with a
      community care provider. The overall aim of this study was to test the discharge
      model designed to assist patients discharged from acute admission wards to adjust
      to community living. This aim was tested through a number of related hypotheses,
      which suggest that, 5 months following discharge from an acute admission ward of
      a psychiatric hospital, individuals participating in a transitional discharge
      model: (1) report fewer symptoms; (2) report better levels of functioning; (3)
      have better quality of life; (4) are less likely to have been re-admitted to
      hospital. The study used a randomized experimental design with two conditions:
      experimental and usual treatment. In general, both the control and the
      experimental group demonstrated significant improvements in symptom severity and
      functional ability after 5 months. Usual treatment subjects in the control group
      were more than twice as likely to be re-admitted to hospital. This study needs to
      be replicated in Scotland with a larger sample and with a modified variation of
      the intervention called the Transitional Care Intervention.

PMID- 14723644
TI  - Pedagogy, power and service user involvement.
AB  - This paper explores mental health nurse educators' perceptions of the involvement
      of service users in preregistration nurse education. The idea for the study was
      developed from a local group of people including service users, lecturers and
      students committed to finding ways to develop service user involvement in
      education. This qualitative study uses semi-structured interviews to explore
      participants' perceptions in depth. Five lecturers who teach on the diploma
      programme based at a large teaching hospital were interviewed. The results
      suggest that the current situation of involving service users at the research
      site was ineffective. The concepts of 'role' and power relationships were used to
      explore the reasons for this. The development of service user involvement in
      education is complex and requires further research.

PMID- 14723645
TI  - Evidence-based uncertainty in mental health nursing.
AB  - The drive towards evidence-based practice is part of a modern reflective and
      caring service. However there is a paradox at the heart of the notion of evidence
      based care. In order to perform any systemized examination of treatment there has
      to be a conscious acknowledgement of uncertainty about that treatment. This is
      uncomfortable and when research does find evidence in favour of a treatment,
      there is a relief and a return to conviction about what is the best. The paradox
      is that it seems the most valued research practices are predicated on
      generalizations about patient treatments and categories. However, nursing care is
      based on the notion of the uniqueness of the patient and the nurse-patient
      relationship. Sometimes it is necessary to address the particular and not to rush
      to generalizations and certainty. The psychoanalytic framework promotes a
      capacity to tolerate uncertainty and provides a model for understanding
      conflicting feelings, which can occur within the nurse-patient relationship. The
      author proposes the psychoanalytic observational method as an adjunct to other
      research methods. This method places certain kinds of evidence within the rubric
      of evidence-based nursing practice. The evidence collected in this method is the
      evidence of the conscious and unconscious experience within the nurse-patient
      relationship. The author will describe and argue for the place of this research
      method within the canon of other more widely practised methods within mental
      health practice. She will propose that for safe practice it is necessary to value
      and examine the veracity of the feelings and tacit understanding of the nurse.
      She contends that the current climate of excessive bureaucracy and persecutory
      risk management is having a damaging effect on both the research process and
      effective nursing care.

PMID- 14723646
TI  - Unreliable evidence.
AB  - As the need for effective evidence-based practice comes under close scrutiny we
      investigate the effectiveness of three interventions; thought suppression,
      reassurance and relaxation, that are routinely offered to clients. These
      strategies have very little evidence to support their continued use. The article
      continues by discussing and describing situations where more helpful evidence
      based interventions are better suited.

PMID- 14723647
TI  - A Meaningful Day Group approach to weight gain from antipsychotic medication.
AB  - For clients who receive medical treatment for a severe and enduring mental health
      problem, antipsychotic medication is the first line of treatment. The adverse
      effects of these medications are well documented and can lead to discontinuation
      of therapy. The newer atypical antipsychotics would seem to have distinct
      advantages over more traditional substances but significant weight gain can be
      experienced. This group is an attempt to capitalize upon psychosocial approaches
      to this such that outcome may be enhanced. The following is a description of an
      attempt to implement such a group and to explore the outcome. The group has been
      devised by one of the manufacturers of atypical antipsychotic medication
      concerned by the side-effect to their product. The group is formatted on a
      computer disc ready to use by any mental health professional and freely
      available.

PMID- 14723648
TI  - The process of implementing evidence-based practice -- the curate's egg.

PMID- 14723649
TI  - David's story.

PMID- 14723651
TI  - Verbal short-term memory in Down's syndrome: an articulatory loop deficit?
AB  - BACKGROUND: Verbal short-term memory, as measured by digit or word span, is
      generally impaired in individuals with Down's syndrome (DS) compared to mental
      age-matched controls. Moving from the working memory model, the present authors
      investigated the hypothesis that impairment in some of the articulatory loop sub
      components is at the base of the deficient maintenance and recall of phonological
      representations in individuals with DS. METHODS: Two experiments were carried out
      in a group of adolescents with DS and in typically developing children matched
      for mental age. In the first experiment, the authors explored the reliance of
      these subjects on the subvocal rehearsal mechanism during a word-span task and
      the effects produced by varying the frequency of occurrence of the words on the
      extension of the word span. In the second experiment, they investigated the
      functioning of the phonological store component of the articulatory loop in more
      detail. RESULTS: A reduced verbal span in DS was confirmed. Neither individuals
      with DS nor controls engaged in spontaneous subvocal rehearsal. Moreover, the
      data provide little support for defective functioning of the phonological store
      in DS. CONCLUSIONS: No evidence was found suggesting that a dysfunction of the
      articulatory loop and lexical-semantic competence significantly contributed to
      verbal span reduction in subjects with DS. Alternative explanations of defective
      verbal short-term memory in DS, such as a central executive system impairment,
      must be considered.

PMID- 14723652
TI  - People with intellectual disability and their health problems: a review of
      comparative studies.
AB  - BACKGROUND: The transition of people with intellectual disability (ID) from care
      institutions to the community - according to Western policy - results in a shift
      of responsibility towards primary health care services. In order to provide
      optimal care to people with ID living in the community, general practitioners
      need to be aware of the specific health problems of this patient category. The
      aim of this paper is to present an overview of recent studies on the specific
      health problems of people with ID, in particular on health problems of people
      with ID in the community, compared to those of the general population. METHOD: To
      reliably compare health problems of individuals with and without ID, this review
      is limited to comparative research using a control group of individuals without
      ID. The focus of the review concentrates on international literature, published
      between 1995 and 2002. RESULTS: Most comparative research among people with ID
      presents higher prevalence rates for epilepsy, diseases of the skin, sensory loss
      and (increased risk of) fractures. These health problems are specific for people
      with ID, both in general and living in the community in particular. CONCLUSIONS:
      there are only few studies focusing on health problems in people with ID in which
      a control group of individuals without ID is included. Most comparative studies
      on health problems in people with ID are based on comparison with reported
      prevalence rates of general health surveys.

PMID- 14723653
TI  - The Resident Choice Scale: a measure to assess opportunities for self
      determination in residential settings.
AB  - BACKGROUND: A 26-item Resident Choice Scale was designed to assess service
      practices for promoting resident choice. METHOD: The staff working with 560
      UK/Irish adults with intellectual disability were interviewed. Specific examples
      of practices promoting resident choice were requested and independently rated by
      the interviewer. RESULTS: The interrater reliability of Resident Choice items was
      found to be acceptable (subsample n = 50). The psychometric properties of the
      Resident Choice Scale total score and scores on eight subscales were also
      acceptable. Consistently strong associations were found between greater resident
      choice and greater resident ability and, to a lesser extent, fewer resident
      challenging behaviours. Few associations were found between resident choice and
      autism or mental health problems. Even when controlling for resident ability and
      challenging behaviour, consistent associations were found between greater
      resident choice and the concurrent variables of greater community presence, fewer
      institutional practices, and greater user self-reported satisfaction (subsample n
      = 50). CONCLUSIONS: Taken together, this pattern of results indicates that the
      Resident Choice Scale shows promise as a measure of the environmental
      opportunities available for adults with intellectual disability to exercise self
      determination. Areas for future research testing the reliability and validity of
      the Resident Choice Scale are outlined.

PMID- 14723654
TI  - Sex differences in performance over 7 years on the Wechsler Intelligence Scale
      for Children--Revised among adults with intellectual disability.
AB  - BACKGROUND: The aim of this study was to explore changes related to sex
      differences on the Wechsler Intelligence Scale for Children - Revised (WISC-R)
      subtest performance over a 7-year interval in middle-aged adults with
      intellectual disability (ID). Cognitive sex differences have been extensively
      studied in the general population, but there are few reports concerning
      individuals with ID. Sex differences are of current relevance to actively debated
      issues such as cognitive changes during menopause and risk for Alzheimer's
      disease. Given that hormonal effects on cognition have been observed in the
      general population, particularly in areas such as visuospatial processing, and
      individuals with Down's syndrome (DS) have been reported to be hormonally and
      reproductively atypical, we analysed our data to allow for the possibility of an
      aetiology-specific profile of sex differences for these adults. METHODS: The WISC
      R subtests were administered in a longitudinal study, as part of a more
      comprehensive test battery, at least twice within 7 years. Participants were 18
      females with ID without DS [age at first test time (time 1): mean = 40.5; IQ:
      mean = 59.3], 10 males with ID without DS (age at time 1: mean = 42.4; IQ: mean =
      59.4), 21 females with DS (age at time 1: mean = 37.9; IQ: mean = 51.6), and 21
      males with DS (age at time 1: mean = 40.3; IQ: mean = 54.3). All participants
      were in the mild to moderate range of ID and were displaying no changes
      suggestive of early dementia. RESULTS: Females, regardless of aetiology of ID,
      exhibited a robust superiority on the coding subtest, which parallels the widely
      reported difference among adults in the general population. Additionally, there
      was a decline in overall performance during the 7-year study interval,
      particularly on the verbal subscale subtests, but there was no evidence of sex
      differentiated decline. There were also marginal sex by aetiology interactions on
      the object assembly and block design subtests, suggesting that males with
      unspecified ID might perform better than their female peers, but among adults
      with DS, females might do better than males. CONCLUSIONS: This study supports the
      presence of cognitive sex differences in the population with ID as indicated by
      female superiority on the WISC-R coding subtest. Extending this observation to
      adults with ID has implications for explanations of female advantage on this
      task, which now have to account for its presence among individuals with a broader
      range of intellectual capabilities, more atypical developmental histories and
      more varied genotypes than previously considered. Trends towards sex by aetiology
      interactions on the two visuoconstructive subtests, while marginal, were
      sufficient to warrant continued consideration of the idea of a distinct profile
      of sex differences for adults with DS and to justify looking at the effects of
      sex separately within different aetiologies of ID.

PMID- 14723655
TI  - Re-injecting spontaneity and balance in family life: parents' perspectives on
      recreation in families that include children with developmental disability.
AB  - METHODS: Grounded in the naturalistic paradigm, a mixed-method research design
      (survey questionnaire, n = 65; and interview, n = 16) was used to explore the
      nature and benefits of, and constraints to, family recreation in families that
      included children with developmental disability. Statistical analyses were
      conducted on the quantitative data, while key theme and constant comparative
      methods were used to analyse the qualitative data. RESULTS: These analyses
      revealed that family recreation most often involved small combinations of family
      members - usually mothers and their children - in physical recreation activities
      (e.g. swimming, walking, bike riding). Parents viewed these interactions as
      beneficial for enhancing family relationships and providing children,
      particularly those with a disability, opportunities for skill and self
      development within an accepting and supportive environment. Difficulties in
      coordinating family members schedules, finding activities to accommodate wide age
      and skill ranges, planning demands, and limitations in marketing and promotional
      materials were among the constraints most commonly identified in relation to the
      family as a whole and the children with developmental disability. Links to
      existing family and leisure research, family systems theory, and considerations
      for future research also are discussed.

PMID- 14723656
TI  - General practitioners' educational needs in intellectual disability health.
AB  - BACKGROUND: The community general practitioner (GP) has a central role in the
      provision of primary health care to people with intellectual disability (ID) as
      an indirect result of deinstitutionalization in Australia. This population,
      however, continues to experience poor health care compared to the general
      population. The current paper describes results from a questionnaire that aimed
      to identify the perceptions of practising GPs on the standards of health care for
      people with ID, the adequacy of prior training, and their interest in further
      education in relation to nine health care areas. METHOD: A questionnaire was
      posted to a selective sample of 1272 practising GPs in Victoria selected from a
      database from the Centre for Developmental Disability Health Victoria and the
      Victorian Medical Directory of GPs registered with the Australian Medical
      Association. Data were available for 252 respondents with a response rate of
      28.5%. RESULTS: The health areas in which many GPs reported to be inadequately
      trained were the same as those areas that were perceived as being of a poor
      standard. These areas were behavioural or psychiatric conditions, human relations
      and sexuality issues, complex medical problems, and preventative and primary
      health care. Ninety four per cent of respondents were interested in further
      education in at least one of the nine health care areas, with the most frequently
      nominated areas being behavioural or psychiatric conditions, syndrome-specific
      medical problems, human relations and sexuality issues and collaboration with
      government services. General practitioners did not nominate complex medical
      problems or preventative and primary health care for further education as
      frequently as they identified care in these areas to be substandard and their
      prior training inadequate. CONCLUSIONS: The findings from the current research
      are discussed in relation to the implications for development of educational
      programmes based on learning needs identified by the GP. The most frequently
      nominated health care areas in all three questions were behavioural or
      psychiatric conditions and human relations and sexuality issues. Reasons for
      incongruence between the frequency of responses for complex medical problems and
      preventative and primary health care are explored.

PMID- 14723657
TI  - Relationship between theory of mind and language ability in children and
      adolescents with intellectual disability.
AB  - BACKGROUND: The present study was designed to evaluate the validity of the false
      belief task as a measure of theory of mind development in individuals with
      intellectual disability (ID). In most if it variants, the false belief task is
      linguistically demanding. This raises the possibility that the finding that
      individuals with ID do poorly on it might reflect language difficulties rather
      than theory of mind difficulties. Complicating matters further, however, is the
      fact that there are theoretical reasons to suppose that there might be a
      relationship between some dimensions of language ability and theory of mind
      development in individuals with ID (as well as in other populations). METHOD: In
      the present study, children and adolescents with ID and typically developing (non
      verbal) mental age matches completed a standard false belief task and several
      tasks designed to measure language ability. RESULTS: We reasoned that a pattern
      in which false belief performance was correlated with all measures of language
      ability would reflect an artefactual relationship, whereas a more highly
      circumscribed, theoretically sensible pattern of correlations that was similar
      across both groups would support the validity of the false belief task.
      CONCLUSIONS: The results indicated that for individuals with ID who have limited
      narrative language skills, those limitations contribute substantially to their
      failure on the false belief task. For individuals with ID who have more highly
      developed narrative language skills (about 40% of the sample tested), however,
      the false belief task may provide a valid measure of their progress towards
      acquiring an adequate theory of mind. This latter conclusion was suggested by the
      fact screening out individuals who failed to meet linguistic and cognitive
      prerequisites for dealing with the performance demands of the false belief task
      yielded non-significant correlations between false belief performance and the
      language measures for both the group with ID and the typically developing
      comparison group.

PMID- 14723658
TI  - Sentence memory of individuals with Down's syndrome and typically developing
      children.
AB  - BACKGROUND: Individuals with Down's syndrome (DS) have an auditory short-term
      memory span disproportionately shorter than the non-verbal mental age (MA). This
      study evaluated the Baddeley model's claim that verbal short-term memory deficits
      might arise from slower speaking rates (and thus less material rehearsed in a 2 s
      passive store) by using the sentence memory subtest of the Stanford-Binet.
      Previous work had shown digit span recall speaking rate to be comparable to the
      examiner's slow rate (one syllable per second) for both DS and language-matched
      participants. METHOD: Thirty individuals with DS were compared to two control
      groups [non-verbal MA-matched and mean length of utterance (MLU)-matched] on the
      sentence span and speaking rate for the longest verbatim recalled sentence.
      Sentence stimuli were presented at a normal speaking rate. RESULTS: The DS group
      had shorter sentence memory span than the MA-matched group and a faster, rather
      than slower, speaking rate (syllables per second) than the MLU-matched controls.
      CONCLUSIONS: Language production level accounted for a substantial portion of the
      variance in the sentence memory span in the DS group. Thus, language production
      skill, rather than speaking rate, predicts variability in verbal memory span.

PMID- 14723659
TI  - Cognitive abilities and genotype in a population-based sample of people with
      Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is characterized by extreme floppiness at
      birth, impaired sexual development, short stature, severe over-eating,
      characteristic physical features and learning disabilities (LD). Impaired social
      cognition, literal mindedness and cognitive inflexibility are also present. The
      syndrome has two main genetic subtypes that both result in the failure of
      expression of maternally imprinted genes on chromosome 15 at the locus q11-13.
      METHODS: Through multiple sources, we attempted to identify all people with PWS
      living in one health region in the UK. Additional people with PWS identified in
      other regions were also recruited to augment the study sample. A comparison group
      of people with LD as a result of aetiologies other than PWS was also identified.
      All people from these three groups, over age three, who gave their consent, were
      assessed using tests of ability and attainment. In addition, their main carers
      were interviewed using a semistructured interview. Blood samples for genetic
      diagnosis were obtained from all consenting participants. FINDINGS: The IQ
      distribution of the population sample was approximately normal with a mean IQ 40
      points below that of the general population. There were systematic differences
      between the two main genetic subtypes. Those with disomies differed in cognitive
      profiles from both those with deletions and the comparison LD group (the latter
      two groups were very similar) in terms of better verbal abilities and impaired
      coding ability. Some people with PWS deletions had strong visuospatial skills.
      INTERPRETATION: We propose that the normal distribution of IQ, shifted downwards
      relative to that of the general population, is the result of a global effect on
      IQ of the PWS gene(s), and that the different cognitive profile seen in those
      with chromosome 15 maternal disomies is a specific effect of a gene, or genes, on
      chromosome 15 which is differentially either expressed or not expressed in those
      with disomies relative to those with deletions. One hypothesis is that these
      subtle cognitive differences are a manifestation of the genetic influences of
      gender-specific imprinted genes on cerebral lateralization. This requires further
      investigation.

PMID- 14723660
TI  - Academic underachievement by people with Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a genetically determined
      neurodevelopmental disorder that is associated with the under-expression of
      maternally imprinted genes at the 15q11-q13 chromosomal locus. In addition to a
      characteristic physical and behavioural phenotype, those with the syndrome have
      impaired social cognition, literal mindedness and inflexibility. The present
      authors investigated the relationship between the PWS cognitive and behavioural
      phenotype, educational experience, and levels of attainment in reading, writing
      and arithmetic. METHODS: All subjects from a population-based sample of people
      with PWS, augmented by those with PWS living in other regions together with a
      contrast group of people with learning disability (LD) of other aetiologies, are
      included in the present study. Those children over 3 years of age whose families
      consented or adults who themselves consented were assessed for ability and
      attainment (over 7 years of age), and information on functional ability was also
      obtained from an informant. Underachievement was defined as the difference
      between the score predicted from full-scale IQ and the actual achievement score.
      RESULTS: Commonly, levels of achievement were lower than would have been
      predicted on the basis of IQ among those in the groups with PWS and LD. In the
      group with PWS, underachievement across academic domains was positively
      correlated with the percentage of time in education in a special school and
      negatively correlated with Vineland Socialization domain standard score. There
      were no across-domain significant correlations in the group with LD. When using
      multiple regression analysis, the percentage of time in special school was the
      only predictor of underachievement and only in the group with PWS. However, some
      children with PWS in special schools did achieve as expected in at least one
      academic domain. CONCLUSIONS: Children with PWS may be placed in special schools
      largely because of their behavioural problems or physical disabilities, or
      expectations based on their PWS status. Their intellectual abilities may well be
      masked by their immature social behaviour. The present authors propose that a
      failure to recognize and address the specific educational needs which follow from
      this combination of poor socialization skills and complex maladaptive behaviours,
      in the context of relatively mild LD, may explain their findings.

PMID- 14723661
TI  - Response to McGrother et al. (Journal of Intellectual Disability Research, 46,
      299-309) 'The prevalence of intellectual disability among South Asian communities
      in the UK'.

PMID- 14723663
TI  - SARS--a perspective from a school of nursing in Hong Kong.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a new infectious disease
      with significant morbidity and mortality that has had a major impact on health
      and health care services worldwide. Hong Kong has had a significant number of
      cases and deaths. Nurses, at the vanguard of the clinical health care team, have
      been particularly affected by it. The outbreak prompted the health authorities to
      implement a series of public health measures and hospital policies, including a
      guideline for the diagnosis and management of patients with SARS. AIMS AND
      OBJECTIVES: This paper aims at providing an overview of what is known about SARS
      and the impact it has had in Hong Kong and to highlight from the perspective of a
      school of nursing the major clinical, educational and public health implications.
      CONCLUSIONS: The lack of understanding and uncertainty about the disease led to
      significant variation in the provision of information, contributing to the
      confusion and anxiety in the community. Therefore, there is a need to revise the
      nursing curriculum, to provide continuing education to all health care
      professionals, particularly with regard to infection control measures, and to
      revisit the range of public health policies to ensure the health of the community
      is protected by these policies. There also has been a reaffirmation of the
      importance of health promotion that highlights the importance of the partnership
      between nurses, health policy makers and public health personnel. It is evident
      that the organization and delivery of clinical practice, teaching and health
      promotion have to be flexible and responsive to a changing health scenario.
      RELEVANCE TO CLINICAL PRACTICE: Nurses must play a crucial role in the
      prevention, detection and containment of SARS. They will need to implement and
      ensure strict adherence to infection control measures and, in some circumstances,
      isolation and quarantine may be warranted. Attention to the psychological state
      of patients and family members should not be overlooked. Paramount is education
      of patients, families and members of the public at large.

PMID- 14723664
TI  - The challenge of spiritual care in a multi-faith society experienced as a
      Christian nurse.
AB  - BACKGROUND: Understanding the spiritual dimension of holistic nursing care is
      arguably regaining its centrality in the assessment of patient well being in
      whatever area of care. However it is argued that we are still far from having a
      universal agreement as to what is meant by the concept of spirituality. AIMS AND
      OBJECTIVES: This paper aims to explore some of the definitions and models of
      spirituality and determine what is meant by spiritual needs. Taking the
      perspective of a Christian nurse, the potential tension between the nature of
      spiritual care and evidence-based professionalism is explored. CONCLUSION: The
      exploration reveals the challenges faced by a nurse who wishes to administer this
      spiritual care and holds a personal commitment to the Christian faith. RELEVANCE
      TO CLINICAL PRACTICE: Acknowledging and debating the challenge of spiritual care
      is arguably the first step towards meeting optimally this need in our patients.
      The dilemma that may need to be further explored within the context of nursing
      care is how a nurse, holding and operating within one particular belief (e.g.
      Christianity) can offer the ideal of spiritual care to patients who hold other,
      quite different beliefs.

PMID- 14723665
TI  - Communication with dying patients--perception of intensive care units nurses in
      Brazil.
AB  - AIMS AND OBJECTIVES: This study aimed to assess whether nurses working in
      intensive care units view the establishment of communication with patients beyond
      therapeutic possibilities as an effective palliative therapeutic resource, and
      which aspects of this communication they valued most. METHOD: Data were collected
      in November 2002, by semi-structured interviews with 10 nurses of both clinical
      and surgical intensive care unit at a school hospital in Sao Paulo city, Brazil.
      Interviews were recorded and transcribed to be further analysed according to the
      qualitative methodology of content analysis. RESULTS: Four categories of thematic
      order raised from the collected statements, which clarify (i) the value of
      communication with terminal patients; (ii) the obstacles found during this
      process; (iii) the need to identify the individual demands of each patient, (iv)
      be able to use communication as a tool in the palliative care of the dying
      patient. CONCLUSION: In conclusion, we found that the nurses working at the
      intensive care unit do consider communication with dying patients an effective
      therapeutic resource, in spite of their own difficulties in communicating with
      dying patients, viewing themselves as ill prepared to the task, and often,
      distancing themselves from the dying patients because of their inability to deal
      with their own feelings, which were brought forth by the confrontation with the
      imminence of death. RELEVANCE TO CLINICAL PRACTICE: Although the number of
      interviewed nurses in our study was small, the results corroborated the findings
      of other studies and revealed an educational aspect in nursing training that
      deserves serious consideration.

PMID- 14723666
TI  - Understanding experience in nursing.
AB  - BACKGROUND: This paper reviews research that considered the life stories of
      experienced nurses and the relationships between life experience, the way in
      which people find meaning in their experience(s), the development of nursing
      knowledge, and the influence of these events and understandings on the
      characteristics and clinical practice of experienced nurses. AIMS AND OBJECTIVES:
      The dominant perspectives in nursing about the place of experience in the
      development of nurses' practice are considered and the paper argues for a broader
      understanding of experience; placing experience within the context of nurses'
      lives, connection with others and their individual understandings about nursing
      care. RELEVANCE TO CLINICAL PRACTICE: The place of experience in the development
      of nurses has not been well understood although the nursing discourse continues
      to value clinical experience highly. Becoming experienced as a nurse is described
      as a progressive and continuous interaction between experience, meaning and the
      lived world resulting in a personal and unique understanding of practice. The
      culture and discourse of nursing have tended to exclude or dampen individual
      difference and the paper considers a more expansive understanding of the place of
      experience and individual difference in nursing and the relevance of this
      perspective for the education of nurses.

PMID- 14723667
TI  - Coronary artery bypass grafting: social support for patients and their
      significant others.
AB  - BACKGROUND: Patients and significant others may experience physical and
      psychological stress symptoms during the recovery time from coronary artery
      bypass surgery. It has been shown that social support is associated with health
      and well-being in various situations. It is important to study how patients and
      significant others describe the social support received. AIM AND OBJECTIVE: To
      describe social support for bypass surgery patients and their significant others
      from the social network and nurses during hospitalization and the association
      between demographic variables and support received from nurses. DESIGN: A
      descriptive study using a questionnaire. This was a pilot study. METHOD:
      Questionnaires were mailed to 146 subjects and 103 responded. The questionnaires
      included background variables, the Social Support from the Social Network Scale
      and the Support from Nurses during Hospitalization Scale. RESULTS: In most cases,
      the spouse, children and friends were the major sources of support for patients
      and significant others. Patients reported equal amounts of both affect and aid or
      concrete support while significant others reported the highest level of affect
      and the lowest level of affirmation from the social network. Patients and
      significant others reported the highest level of affirmation and the lowest level
      of aid from nurses during hospitalization. CONCLUSIONS: Relatives are important
      sources of support for bypass surgery patients and their significant others.
      Patients reported higher levels of all types of social support from both the
      social network and nurses than did significant others. RELEVANCE TO CLINICAL
      PRACTICE: The provision of nursing support for significant others can be enhanced
      by focusing nursing care on the whole family. This would promote the health of
      the whole family.

PMID- 14723668
TI  - Coronary heart disease: causes and drug treatment--spouses' conceptions.
AB  - BACKGROUND: Spouses are important in the rehabilitation process of their partner
      after coronary heart disease event. Their knowledge and attitudes have an impact
      on their support to the partner concerning lifestyle changes and drug treatment
      after an event. AIMS AND OBJECTIVES: To explore spouses' conceptions concerning
      causes of coronary heart disease and drug treatment 1 year after the partner's
      cardiac event. DESIGN: Qualitative with an empirical and inductive approach.
      METHODS: Semi-structured interviews with strategically selected spouses (17 women
      and eight men) were taped. The transcripts were analysed within the
      phenomenographic framework. RESULTS: Spouses' conceptions about causes of
      coronary heart disease and its treatment consisted of correct facts, as judged on
      a lay level, less elaborated conceptions and misconceptions. Among causes of
      coronary heart disease, the spouses were most knowledgeable about fat intake.
      They knew less about contributions from inactivity, stress and smoking.
      Ambivalent feelings were expressed about benefits vs. side effects of drugs. The
      treatment was conceived as necessary for the heart, but harmful for other organs.
      Men and women were evenly distributed in most of the derived categories. More
      women than men considered stress as a cause of coronary heart disease and also
      misconceived physical exercise to cause the disease. CONCLUSION: A variation of
      spouses' conceptions was revealed about causes of coronary heart disease and drug
      treatment. There was a lack of understanding concerning important parts of
      cardiac rehabilitation activities. These misconceptions may have implications by
      influencing their partner's co-operative behaviour. RELEVANCE TO CLINICAL
      PRACTICE: Spouses' pre-existing conceptions of coronary heart disease and its
      treatment should be considered in the rehabilitation process of their partner.
      Couples with misconceptions should be given the opportunity to increase
      qualitatively their knowledge starting from their point of view rather than from
      that of the professional perspective.

PMID- 14723669
TI  - Cardiac rehabilitation: the importance of patient expectations--a practitioner
      survey.
AB  - BACKGROUND: Numerous cardiac rehabilitation national guidelines consistently
      endorse the need for psychological support to create effective individualized
      care. Recent surveys suggest that the psychological factors remain poorly
      assessed and the measurement of psychological parameters remains patchy. AIM: To
      examine cardiac rehabilitation practitioners' perception and understanding of the
      importance of patient expectations and their capacity to assess and utilize these
      expectations to develop individualized care. METHODS: A survey of cardiac
      rehabilitation professionals from 10 hospitals in the south-east of England. The
      questionnaire used in the survey was developed from content analyses of the
      current cardiac rehabilitation literature and expectancy theory articulated in
      Bandura's writings. RESULTS: The results of the study show that cardiac
      rehabilitation practitioners are very aware of the general importance of patient
      expectations but have little structured support in the development of techniques
      to either assess these expectations or to utilize them in a therapeutic context.
      This leaves them unsure about the extent to which patients do receive
      individualized care and how best to develop their own practice in this regard.
      RELEVANCE TO CLINICAL PRACTICE: This study suggests that there is a need for the
      development of a structured assessment tool, which has a sound theoretical basis
      to assess patients' expectation if good practice is to be established in
      providing individualized car in cardiac rehabilitation.

PMID- 14723670
TI  - Palliative care in a coronary care unit: a qualitative study of physicians' and
      nurses' perceptions.
AB  - BACKGROUND: Earlier research has shown that physicians and nurses are motivated
      to provide good palliative care, but several factors prevail that prevent the
      best care for dying patients. To provide good palliative care it is vital that
      the relationship between nurses and physicians is one based on trust, respect and
      sound communication. However, in settings such as a coronary care unit,
      disagreement sometimes occurs between different professional groups regarding
      care of dying patients. AIM AND OBJECTIVES: The aim of this study was to describe
      and understand physicians' and nurses' perceptions on their working relationship
      with one another and on palliative care in a coronary care unit setting. DESIGN:
      Using a convenience sample, professional caregivers were interviewed at their
      work in a coronary care unit in Sweden. METHODS: Data collection and analysis
      were done concurrently using a qualitative approach. RESULTS: From the
      interviews, a specific pattern of concepts was identified. The concepts were
      associated with a dignified death, prerequisites for providing good palliative
      care and obstacles that prevented such care. CONCLUSIONS: Caregivers who work in
      a coronary care unit are highly motivated to provide the best possible care and
      to ensure a dignified death for their patients. Nevertheless, they sometimes fail
      in their intentions because of several obstacles that prevent good quality care
      from being fully realized. RELEVANCE TO CLINICAL PRACTICE: To improve practice,
      more attention should be paid to increasing dying patients' well-being and
      participation in care, improving strategic decision-making processes, offering
      support to patients and their relatives, and improving communication and
      interaction among caregivers working in a coronary care unit. Caregivers will be
      able to support patients and relatives better if there are good working relations
      in the work team and through better communication among the various professional
      caregivers.

PMID- 14723671
TI  - The effects of age on quality of life in implantable cardioverter defibrillator
      recipients.
AB  - BACKGROUND: The implantable cardioverter defibrillator shows superiority over
      conventional pharmacological therapy. The implantable cardioverter defibrillator
      has been implanted with increasing frequency in patients who are either at risk
      for or have experienced a life-threatening dysrhythmia. Implantable cardioverter
      defibrillator recipients experience a myriad of physical, emotional and social
      adjustments, with little being known about the impact of age on trajectory. AIMS,
      OBJECTIVES AND DESIGN: Therefore the purpose of the study is to examine the
      effects of age on health status, quality of life, and mood states of implantable
      cardioverter defibrillator recipients during the first year after implantation
      using a repeated measures design. METHODS: A comparison of implantable
      cardioverter defibrillator patients' scores with other samples, both ill and
      well, are discussed to see how the two implantable cardioverter defibrillator age
      groups compare on the various measures. Human subjects approval was obtained from
      the institutional review board. RESULTS: Seventy subjects, 51 males and 19
      females, were recruited. There were 31 subjects between the ages of 21 and 62
      years, mean age of 51 years, that comprised the younger age group, and 39
      subjects between the ages of 67 and 84 years, mean age of 74 years, that
      comprised the older age group. Each subject completed the Medical Outcomes SF-36,
      the Ferrans and Powers Quality of Life Index, and the Profile of Moods States at
      time of implantable cardioverter defibrillator implantation, and 6 and 12 months
      later. CONCLUSIONS: The older age group was as expected less physically active,
      less satisfied with their physical functioning, and had slightly more anxiety at
      6 and 12 months than the younger counterparts. The younger implantable
      cardioverter defibrillator recipients demonstrated some improvements over time in
      the perception of their physical adjustment and anxiety. RELEVANCE TO CLINICAL
      PRACTICE: Comparison of the SF-36 with other populations with or without a
      medical condition revealed scores below norms in physical health for both groups,
      and only slightly higher than patients with heart failure for the older group.

PMID- 14723672
TI  - The HRQoL of renal transplant patients.
AB  - BACKGROUND: After undergoing kidney transplant surgery, patients face many new
      challenges. For example, they face new pathologies associated with the complex
      medical regimens that they will need to follow rigorously for the rest of their
      lives. They live with the uncertainty and fear of organ rejection. They will also
      need to acquire new skills to take care of themselves, such as recognizing the
      signs and symptoms of impending infection and rejection. This suggests that once
      a transplant has been performed and the patient has been discharged with a
      functioning graft, the patient must continue to deal with a life of chronic
      illness. AIM: The aim of this study was to explore health-related quality of life
      of Chinese kidney transplant patients in Hong Kong. METHODS: Non-structured
      interviews were conducted. The transcripts were analysed by qualitative content
      analysis. Codes were used to identify a passage of text that the researcher
      interprets as having a particular meaning. Data analysis is an iterative process.
      The codes emerging from each new interview were analysed together with the codes
      which had previously emerged. Across the dataset, codes were compared for
      similarities and differences, both within and across interviews. Codes of common
      property were clustered into categories. The transcripts were re-read and checked
      against the categories until there was no more to be gleaned, and the titles of
      the categories reflected the totality of that experience. Interviews were
      conducted until unique categories were no longer identified. There were 31
      participants. RESULTS: The participants are complying with medication regimens
      and nursing recommendations. Although new symptoms related to the medication
      regime surfaced, participants commented that they improved markedly in physical
      and social functioning, and have a better quality of life as a whole.
      Participants expressed their needs regarding information on the side effects of
      medications, proper exercise and diet. CONCLUSIONS: To optimize post-transplant
      quality of life, a follow-up rehabilitation programme is recommended. RELEVANCE
      TO CLINICAL PRACTICE: Rich and meaningful insights about the perceptions and
      experiences of renal patients after transplantion can be obtained in this study.
      Having known the real needs of patients, nurses can develop strategies to help
      patients to cope with the demands of life with a renal graft, from the early days
      of convalescence to re-integration into work, family responsibilities and life
      beyond.

PMID- 14723673
TI  - Nephrology nursing: blurring the boundaries: the reality of expert practice.
AB  - BACKGROUND: Expertise in nursing has been widely studied; there have been no
      previous studies into what constitute expertise in nephrology (renal) nursing.
      This paper describes a 'real-world' characteristic of expert nephrology nursing
      practice. AIMS AND OBJECTIVES: This paper, which is abstracted from a larger
      study into the acquisition and exercise of nephrology nursing expertise, aims to
      explore the concept blurring the boundaries. DESIGN: The study utilized grounded
      theory methodology and symbolic interactionism. METHODS: The study took place in
      one renal unit in New South Wales. Sampling was purposive then theoretical; the
      sample consisting of six non-expert and eleven expert nurses. Simultaneous data
      collection and analysis using participant observation, review of nursing
      documentation and semi-structured interviews was undertaken. RESULTS: The study
      revealed that only expert nephrology nurses 'blurred the boundaries' of
      professional nursing practice. They did this by moving intermittently and
      purposefully, for the benefit of particular patients, into medical domains in the
      areas of prescribing, dispensing and ordering of pathology tests. Non-expert
      nurses did not cross these professional boundaries. CONCLUSIONS: Blurring the
      boundaries was a significant feature of expert nursing practice, and this study
      was the first to describe explicitly nursing boundaries as two distinct entities;
      that is, formal and informal. RELEVANCE TO CLINICAL PRACTICE: There are some
      nephrology nurses who have sufficient knowledge and experience to prescribe some
      medications and to order certain investigations.

PMID- 14723674
TI  - Chronic renal failure: assessing the Fatigue Severity Scale for use among
      caregivers.
AB  - BACKGROUND: Quality of life for caregivers of end-stage renal disease patients
      has not been well addressed yet the physical and psychological status of this
      overlooked group can be important in the recovery or adaptation of patients with
      chronic renal failure, not to mention the caregivers themselves. One particular
      feature of the overall quality of life of such caregivers is that of fatigue.
      AIMS AND OBJECTIVES: The purpose of the study was to test the Fatigue Severity
      Scale for potential usefulness in assessing fatigue among a non-medical
      population, caregivers of end-stage renal disease patients. METHODS: Subjects
      completed a short battery of measures at either a dialysis centre or at home.
      RESULTS: The Short Form-12 of the Short Form-36 and the Center for Epidemiologic
      Studies Depression Scale accounted for 56% of the variance on the Fatigue
      Severity Scale. The results suggest that physical fatigue may be more prominent
      than mental fatigue as a feature of caregiver quality of life. CONCLUSIONS: The
      Fatigue Severity Scale which has been used for multiple sclerosis patients may
      prove to be useful as a short assessment of fatigue among the non-medical
      population of end-stage renal disease caregivers. This may result in improved
      interventions for the population of caregivers. RELEVANCE TO CLINICAL PRACTICE:
      Physicians, nurses and allied health professionals will be called on more
      frequently to assess and intervene with fatigued and overburdened caregivers in
      addition to patients themselves. A more thorough understanding of the nature of
      caregiver fatigue may drive changes or innovations with caregivers who are too
      often overlooked in the current era of scarce resources. Accordingly results of
      the study suggest that the direction in intervention may focus more on rest and
      respite as opposed to a need for psychosocial support or counselling. While there
      are various modes for assessing end-stage renal disease caregivers' fatigue, a
      simple measure like the Fatigue Severity Scale is brief enough to be administered
      without undue demand on practitioners or caregivers.

PMID- 14723675
TI  - Advanced home care: patients' opinions on quality compared with those of family
      members.
AB  - BACKGROUND: Advanced medical care in the patient's home setting is becoming more
      common. Many of the patients who receive this kind of care have severe illnesses
      and are unable to respond to questions about the quality of care. The research
      question was: are the patients' opinions congruent with those of family members?
      AIM: To explore and compare the relationship between patients' perception of the
      quality of care and close family members' perception of this care as well as
      their perception of the patients' perception. METHODS: Sixty-seven patients
      receiving advanced home care, 82 family members (54 matched patient + family
      member pairs) participated. Data were collected using a short version of the
      quality from the patient's perspective questionnaire modified to advanced home
      care. RESULTS: A high degree of perceptual congruence was found between patients
      and their family members. The similarity was also high between family members'
      own opinion and their appraisal of how the patient perceived the care. A subgroup
      of family members who met the patient once a week or less often deviated from
      this pattern. CONCLUSION: Patients' views on the quality of care are congruent
      with the opinions of family members if they meet every day (live together) and
      share the same everyday and care-related experiences. The results can be
      understood in the light of empathic accuracy theory. RELEVANCE TO CLINICAL
      PRACTICE: The findings of this study have important implications for clinical
      nursing practice. Family members' perception of the quality of care may be a
      valuable data source for nurses in the case of advanced home care if the patient
      and family member share the same everyday, care-related experiences, otherwise
      family members' perception tend to be more critical than those of the patients
      themselves.

PMID- 14723676
TI  - Rheumatology: the expectations and preferences of patients for their follow-up
      monitoring care: a qualitative study to determine the dimensions of patient
      satisfaction.
AB  - BACKGROUND: Patient satisfaction has rarely been defined. It is a multi
      dimensional concept and relates to expectations and preferences for care. This
      paper reports the findings of a study to determine the expectations and
      preferences of rheumatology patients for their follow-up monitoring care. AIMS
      AND OBJECTIVES: To identify the dimensions of satisfaction important to
      rheumatology patients in the provision of their care in two locations; primary
      and secondary. The objectives were to determine the expectations and preferences
      of this group and to gather data to inform a larger study of patient
      satisfaction. DESIGN: This small qualitative study used semi-structured
      interviews with a convenient sample of 10 patients; five from each location.
      METHODS: Interviews were recorded and transcribed. Qualitative data analysis
      revealed a framework and conceptual categories. RESULTS: Empathy, specialism,
      information provision, technical aspects, time, and continuity of care were
      identified as being important in the provision of care for this group of
      patients. CONCLUSIONS: These categories had already been found in a validated
      questionnaire and justified the use of this tool in the larger comparative study.
      RELEVANCE TO CLINICAL PRACTICE: Patient satisfaction cannot be accurately
      assessed unless important categories of care are identified and used in the
      measurement tool.

PMID- 14723677
TI  - Day surgery: patients' perceptions of a nurse-led preadmission clinic.
AB  - BACKGROUND: Previous research studies have demonstrated that nursing intervention
      is often lacking in the provision of adequate information and psychological
      support, and fails to meet the holistic needs of patients in the preassessment
      for day surgery. AIM: The aim of this study was to elicit patients' perceptions
      of the preassessment preparation they received prior to day surgery. METHOD: A
      hermeneutic phenomenological research approach was utilized to elucidate the
      participants' experiences of the preassessment process and to collect data.
      Qualitative data were collected using face-to-face interviews and analysed
      thematically following procedures expounded by Colaizzi and van Manen. SAMPLE:
      The sample included 30 patients undergoing day surgery in a large teaching
      hospital in the north of England. The day unit built for this purpose consisted
      of a preassessment unit, a seated preoperative area, three theatres, a six space
      first stage recovery area, a 24 space second stage recovery area and a separate
      seated recovery area. The patient groups focused on individuals scheduled for
      general surgery, gynaecology and urology procedures. RESULTS: Findings suggest
      that the nurse-led clinic appeared to function effectively; most patients felt
      they were adequately assessed and prepared for day surgery. The majority reported
      receiving comprehensive information about procedures, appreciated health
      education interventions and had opportunity to ask questions. A few patients
      pointed to deficits in information giving, indicating that their individual needs
      were not met, leaving them feeling anxious. Others alluded to problems associated
      with unexpected cancellation of procedures, which threw them into states of
      disequilibrium. RELEVANCE FOR CLINICAL PRACTICE: The findings indicate that
      information giving, psychological support and person-centred care could be
      strengthened in the preassessment preparation of patients undergoing day surgery.

PMID- 14723678
TI  - Haematological cancer patients: achieving a sense of empowerment by use of
      strategies to control illness.
AB  - BACKGROUND: The role that empowerment plays through involving haematological
      cancer patients and their families in their treatment and care is undeniable. It
      encompasses the implementation of various strategies to achieve a sense of
      empowerment. AIMS AND OBJECTIVES: This phenomenological study sought to identify
      core strategies used by cancer patients regardless of their illness stage and
      prognosis who exhibited a strong sense of empowerment in coping with their
      condition. DESIGN: A phenomenological approach using an in depth interviewing
      technique was used to identify the common factors which patients and spouses
      believed could enable them to achieve a measure of control in managing their
      illness. These measures were referred to as coping strategies. METHODS: It was
      decided to conduct a purposive study and re-interview seven of 12 patients who
      had previously participated in a pilot Haematology Shared Care project and who
      had developed a high level of ability in coping with their illness. At the
      patient's discretion, spouses were invited to participate and to contribute to
      the interview. Three spouses participated in the interviewing process. RESULTS:
      Common strategies emerged regardless of the patient's stage of illness and
      prognosis. Informants identified the determination to remain in control of the
      illness and treatment side effects, having the support of family and significant
      others, illness acceptance and maintaining hope as crucial to their sense of
      empowerment. RELEVANCE TO CLINICAL PRACTICE: It is hoped that clinicians will
      gain a deeper understanding of the varied and numerous strategies used by cancer
      patients in coping with their illness. This understanding will ensure that by
      encouraging these strategies, patients and their families will be supported by
      health professionals to achieve a greater sense of empowerment. As this and other
      studies have shown, working alongside health professionals contributes to
      empowerment for both the cancer patient and significant others in their lives.

PMID- 14723679
TI  - Chronic illness self-management: taking action to create order.
AB  - BACKGROUND: This paper presents research that was framed by our early
      understandings about the ways that people incorporate the consequences of illness
      into their lives. The word 'transition' has been used to describe this process.
      We believed self-management to be central to the transition process but this
      assertion required further research, hence this paper. AIM: The research aimed at
      understanding the way in which people who lived with chronic illness constructed
      the notion of self-management. While the participants of this study were living
      with arthritis, the focus was on understanding the meaning of self-management
      rather than the experience of living with the symptoms of arthritis. APPROACH:
      Data were generated when nine people living with arthritis were invited to write
      an autobiography about their life and experiences of living with illness. Two
      telephone interviews were recorded with each participant and then the research
      group (researchers and participants) convened for a discussion meeting. FINDINGS:
      In contrast to health professionals who identify self-management as structured
      education, participants identified self-management as a process initiated to
      bring about order in their lives. Creating a sense of order, or self-management,
      had four key themes (i) Recognizing and monitoring the boundaries, (ii)
      Mobilizing the resources, (iii) Managing the shift in self-identity, (iv)
      Balancing, pacing, planning and prioritizing CONCLUSIONS: People learned about
      their responses to illness through daily life experiences and as a result of
      trial and error. They reconfigured their daily lives and reconstructed their self
      identity by exploring their personal limitations or boundaries. Self-management
      of chronic illness has been considered as both structure and process, however it
      is the process of self-management that we contend is central to the experience of
      transition. RELEVANCE TO CLINICAL PRACTICE: Clinical nursing intervention for
      people with a long term illness may be enhanced when self-management is
      approached from a broad, contextual perspective and self-management processes are
      integrated into clinical practice. The challenge is for nurses to embrace
      processes in nursing practice that will facilitate interactions with clients
      without obstructing the diversity of perspectives, create an environment
      conducive to learning and engage individuals in identifying self-management
      strategies that have meaning in their lives.

PMID- 14723682
TI  - Diagnostic PCR: making internal amplification control mandatory.

PMID- 14723683
TI  - Peptidase activity in various species of dairy thermophilic lactobacilli.
AB  - AIMS: The aim of the present work was to evaluate the enzymatic potential
      manifested by aminopeptidase activity of different thermophilic Lactobacillus
      biotypes and to measure the influence of cell growth phase on enzyme expression.
      METHODS AND RESULTS: The activities were evaluated by the hydrolysis of beta
      naphthylamide substrates for both whole and mechanically disrupted cells of L.
      helveticus, L. delbrueckii subsp. bulgaricus and L. delbrueckii subsp. lactis
      strains, collected from both the exponential and the stationary growth phase. In
      general, activities were higher for cells in the exponential rather than in the
      stationary phase and the disrupted cells showed higher activities than the whole
      cells. The highest activity expressed by all strains corresponded to X-prolyl
      dipeptidyl aminopeptidase while a moderate activity was observed towards Arg
      betaNa, Lys-betaNa and Leu-betaNa. The lowest activity was observed for Pro
      betaNa. CONCLUSIONS: It may be inferred that the cell structure and the cell
      physiology are crucial to define the level of efficiency of expression for
      aminopeptidase activity. The two species may be characterized by a different
      enzymatic system that hydrolyses N-terminal leucine. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The differences of peptidase activities in L. helveticus and L.
      delbrueckii species acquires an importance to comprehend their role in the
      biochemical events occurring in cheese ripening.

PMID- 14723684
TI  - Relationship between interaction sites in the gut, hydrophobicity, mucosal
      immunomodulating capacities and cell wall protein profiles in indigenous and
      exogenous bacteria.
AB  - AIMS: To investigate whether there is a relationship between interaction sites in
      the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall
      protein profiles in lactobacilli, bifidobacteria and enterococci. METHODS AND
      RESULTS: Hydrophobicity, cell wall protein profiles and sites of interaction in
      the gut (by using fluorescein isothiocyanate-labelled bacteria) were determined
      for Lactobacillus casei, L. acidophilus, L. fermentum, Bifidobacterium bifidum,
      B. animalis and Enterococcus faecalis. We also determined the number of
      immunoglobulin (Ig)A+, tumour necrosis factor (TNF)alpha+, interleukin (IL)-6+
      and IL-10+ cells after oral administration of the above bacteria to BALB/c mice.
      All strains assessed were found to interact with the sites of induction of the
      immune response in the gut. No correlation with hydrophobicity was observed. When
      some strains at certain doses were administered to mice, bacterial translocation
      to liver was observed. The oral administration of indigenous (104 cells day(-1))
      and exogenous (107 cells day(-1)) bifidobacteria and lactobacilli for 5
      consecutive days activated the systemic and intestinal mucosal immune response in
      a strain-specific way, independently whether the strain was indigenous or
      exogenous in relation to the host. The differences in the immunopotentiating
      capacity of the various strains might be related to the differences in their cell
      wall protein profiles. CONCLUSIONS: Indigenous bacteria activated the mucosal
      immune response at a dose significantly smaller than the one required for
      probiotic exogenous bacteria. However, probiotic exogenous bacteria can be used
      at high concentrations in fermented dairy products with a great impact on the
      immune system, favouring its immunomodulation. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The immunomodulation capacity of probiotic bacteria is strain specific and
      independent of the specificity of the host. The ability of certain strains to
      down-regulate the production and release of IL-6 by IL-10 may have potential
      implications in their use in cases in which cytokine deregulation or excessive
      production at the mucosal level can be the cause of tissue damage.

PMID- 14723685
TI  - The synergistic effect of EDTA/antimicrobial combinations on Pseudomonas
      aeruginosa.
AB  - AIMS: To demonstrate that the nonlinear concentration-dependent inhibition of
      Pseudomonas aeruginosa to EDTA can be used to successfully model and predict the
      potentiation of antimicrobials by EDTA. METHODS AND RESULTS: A model used
      successfully to describe the concentration-dependent inhibition of bacterial
      growth caused by many antimicrobials was unable to describe the inhibition of P.
      aeruginosa by EDTA. Examination of the inhibition profiles for EDTA against P.
      aeruginosa revealed a biphasic inhibitory pattern suggesting different mechanisms
      of action at different concentrations. A modelled, two-stage inhibitory process
      was shown to fit the observations. This model was then used to examine the effect
      of combining EDTA with other antimicrobials. The apparent synergy of mixtures of
      EDTA with quaternary ammonium surfactants (QAC) and specific antibiotics was
      successfully modelled. Minimum inhibitory concentrations (MIC) of the QAC and
      that of oxacillin and cefamandole were reduced by a factor of 3-10, whereas
      ampicillin was reduced by a factor of 70 from an MIC of 1524 to 21 mg l(-1) in
      the presence of 500 mg l(-1) of EDTA. CONCLUSIONS: A nonlinear concentration
      dependent inhibition of P. aeruginosa by EDTA gives rise to apparent observation
      of synergy with other antimicrobials. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      is a further example where the current methodology for the examination of
      antimicrobial synergy (the summed fractional inhibitory concentrations) leads to
      false conclusions.

PMID- 14723686
TI  - Formation and regeneration of protoplasts in Sclerotium rolfsii ATCC 201126.
AB  - AIMS: Different cultural conditions for forming and reverting protoplasts were
      systematically studied to establish a rapid and efficient protocol for Sclerotium
      rolfsii ATCC 201126. METHODS AND RESULTS: Osmotic stabilizer, lytic enzymes and
      mycelial age were the main factors influencing protoplast yields. An optimized
      protocol involving 1-h hydrolysis of 45-h-old mycelium with Trichoderma harzianum
      enzymes in a 1 : 1 (w/w) biomass : enzyme ratio and 0.6 mol l-1 MgSO4 as osmotic
      stabilizer was designed to produce approx. 2 x 109 protoplasts per gram biomass
      dry weight, with 99% viability. Differences on the lytic activity between batches
      of commercial enzymes were clearly evidenced. Protoplast release was highly
      efficient showing no remaining cell wall material as witnessed by fluorescent
      brightener 28. Up to 26% of purified protoplasts developed into the typical
      filamentous form after 50 h of incubation on 0.6 mol l-1 sucrose agar media.
      CONCLUSIONS: The methodology herein proposed allowed a rapid, inexpensive and
      efficient protoplast production. Optimum yields were higher or in the order of
      that elsewhere reported for other S. rolfsii strains and the required lytic time
      was significantly shorter. Purified protoplasts successfully reverted to the
      filamentous morphology. SIGNIFICANCE AND IMPACT OF THE STUDY: The present
      research reports the former protocol for the isolation and reversion of
      protoplasts in S. rolfsii ATCC 201126 providing key factors to ensure optimum
      results. In addition, the described procedure constitutes a starting point for
      downstream genetic manipulation.

PMID- 14723687
TI  - PCR-DGGE fingerprints of microbial succession during a manufacture of traditional
      water buffalo mozzarella cheese.
AB  - AIMS: To monitor the process and the starter effectiveness recording a series of
      fingerprints of the microbial diversity occurring at different steps of
      mozzarella cheese manufacture and to investigate the involvement of the natural
      starter to the achievement of the final product. METHODS AND RESULTS: Samples of
      raw milk, natural whey culture (NWC) used as starter, curd after ripening and
      final product were collected during a mozzarella cheese manufacture. Total
      microbial DNA was directly extracted from the dairy samples as well as bulk
      colonies collected from the plates of appropriate culture media generally used
      for viable counts of mesophilic and thermophilic lactic acid bacteria (LAB) and
      used in polymerase chain reaction-denaturing gradient gel electrophoresis (PCR
      DGGE) experiments. The analysis of the DGGE profiles showed a strong influence of
      the microflora of the NWC on the whole process because after the starter
      addition, the profile of all the dairy samples was identical to the one shown by
      the NWC. Simple indexes were calculated for the DGGE profiles to have an
      objective estimation of biodiversity and of technological importance of specific
      groups of organisms. LAB grown on Man Rogosa Sharp (MRS) and Rogosa agar at 30
      degrees C showed high viable counts and the highest diversity in species
      indicating their importance in the cheese making, which had not been considered
      so far. Moreover, the NWC profiles were shown to be the most similar to the curd
      profile suggesting to be effective in manufacture. CONCLUSIONS: The PCR-DGGE
      analysis showed that in premium quality manufacture the NWC used as starter had a
      strong influence on the microflora responsible for process development.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The molecular approach appeared to be valid
      as a tool to control process development, starter effectiveness and product
      identity as well as to rank cheese quality.

PMID- 14723688
TI  - Oxidation-reduction potential regulates RpoS levels in Salmonella Typhimurium.
AB  - AIMS: The aim of this work was to investigate the connection between oxidation
      reduction (redox) potential and stationary phase induction of RpoS in Salmonella
      Typhimurium. METHODS AND RESULTS: A lux-based reporter was used to evaluate RpoS
      activity in S. Typhimurium pure cultures. During growth of S. Typhimurium, a drop
      in the redox potential of the growth medium occurred at the same time as RpoS
      induction and entry into stationary phase. An artificially induced decrease in
      redox potential earlier during growth reduced the time to RpoS induction and
      Salmonella entered the stationary phase prematurely. In contrast, under high
      redox conditions, Salmonella grew unaffected and entered the stationary growth
      phase as normal, although RpoS induction did not occur. As a consequence,
      stationary phase cells grown in the high redox environment were significantly
      more heat sensitive (P < 0.05) than those grown under normal conditions.
      CONCLUSIONS: This work suggests that redox potential can regulate RpoS levels in
      S. Typhimurium and can thus, control the expression of genes responsible for
      thermal resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to
      manipulate RpoS induction and control stationary phase gene expression can have
      important implications in food safety. Early RpoS induction under low redox
      potential conditions can lead to enhanced resistance in low cell concentrations
      to inimical processes such as heat stress. Inhibition of RpoS induction would
      abolish stationary phase protective properties making cells more sensitive to
      common food control measures.

PMID- 14723689
TI  - The composition and persistence of faecal coliforms and enterococcal populations
      in sewage treatment plants.
AB  - AIMS: The changes in structure and composition of faecal coliforms and
      enterococcal populations in sewage from different treatment plants, and the
      elimination of vancomycin- and erythromycin-resistant enterococci (VRE and ERE,
      respectively) in these treatment plants was analysed to determine any selective
      reduction. METHODS AND RESULTS: Faecal coliforms, enterococci, VRE, ERE and
      spores of sulphite-reducing bacteria were enumerated using standard methods.
      Samples were enriched where necessary in order to isolate antibiotic resistant
      strains. The structure and composition of these bacterial populations were
      determined by biochemical fingerprinting and clustering analysis. High diversity
      and similarity indexes were detected among all the bacterial populations in raw
      and treated sewage, independently of their origin and the treatment processes
      employed. Antibiotic resistant strains were detected in all sewage tested and no
      selective reduction was observed. CONCLUSIONS: The faecal coliforms and
      enterococci populations did not differ in the sewage samples studied. The
      vancomycin and erythromycin resistances of the enterococcal populations were
      similar in the sewage samples. Resistance to both antibiotics persisted after the
      treatment process independently of raw sewage flow, faecal origin or size of the
      human population contributing to sewage. However, sewage of mixed origin (human
      and animal) presented a lower similarity index for the two bacterial populations
      compared with that of the other human sewage analysed. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Although a significant reduction in bacterial populations was
      observed, the persistence of VRE and ERE strains in the same proportions in
      sewage suggests that there is no selective elimination of bacterial populations
      during the treatment processes. The ability of antibiotic resistance strains to
      survive sewage treatment systems should be considered in certain water reuse
      programmes.

PMID- 14723690
TI  - Mechanisms of killing of Bacillus subtilis spores by Decon and Oxone, two general
      decontaminants for biological agents.
AB  - AIMS: To determine the mechanisms of Bacillus subtilis spore killing by and
      resistance to the general biological decontamination agents, Decon and Oxone.
      METHODS AND RESULTS: Spores of B. subtilis treated with Decon or Oxone did not
      accumulate DNA damage and were not mutagenized. Spore killing by these agents was
      increased if spores were decoated. Spores prepared at higher temperatures were
      more resistant to these agents, consistent with a major role for spore coats in
      this resistance. Neither Decon nor Oxone released the spore core's depot of
      dipicolinic acid (DPA), but Decon- and Oxone-treated spores more readily released
      DPA upon a subsequent normally sublethal heat treatment. Decon- and Oxone-killed
      spores initiated germination with dodecylamine more rapidly than untreated
      spores, but could not complete germination triggered by nutrients or Ca(2+)-DPA
      and did not degrade their peptidoglycan cortex. However, lysozyme treatment did
      not recover these spores. CONCLUSIONS: Decon and Oxone do not kill B. subtilis
      spores by DNA damage, and a major factor in spore resistance to these agents is
      the spore coat. Spore killing by both agents renders spores defective in
      germination, possibly because of damage to the inner membrane of spore.
      SIGNIFICANCE AND IMPACT OF STUDY: These results provide information on the
      mechanisms of the killing of bacterial spores by Decon and Oxone.

PMID- 14723691
TI  - Genetic characterization of Erwinia amylovora strains by amplified fragment
      length polymorphism.
AB  - AIMS: Erwinia amylovora is one of the most important pathogens of pear and apple
      and is subject to strict quarantine regulations worldwide, although its patterns
      of dispersal are largely unknown. Previous attempts to fingerprint E. amylovora
      strains by molecular techniques have detected very little polymorphism because of
      the high genetic homogeneity of this bacterium. Our aim was to establish and test
      a typing method to quantify genetic diversity among strains of this plant
      pathogen. METHODS AND RESULTS: Twenty-two strains from different hosts and
      geographical locations were examined by PCR fingerprinting with four primers and
      by amplified fragment length polymorphism (AFLP) with four selected combinations
      of primers with a single base extension. PCR fingerprinting revealed little
      polymorphism producing the same amplification patterns for 17 strains, while the
      combined AFLP patterns yielded 78 polymorphic bands (34% of total bands) and
      allowed the differentiation of all but two strains. Clustering of strains in the
      resulting dendrogram was not correlated with host, year or country of isolation,
      and questions previous genealogies based on PFGE patterns. CONCLUSIONS: The AFLP
      technique allowed the detection of an unprecedented number of genetic markers in
      E. amylovora and proved to be the most useful tool so far for discriminating
      among strains of this pathogen. The results obtained in this study strongly
      suggest the occurrence of multiple introductions of the pathogen in Spain and
      other European countries. SIGNIFICANCE AND IMPACT OF THE STUDY: A major
      limitation in understanding the ecology of fire blight is the lack of typing
      techniques with a high power of discrimination. This study demonstrates the high
      resolution and the usefulness of the AFLP technique to differentiate among E.
      amylovora strains.

PMID- 14723692
TI  - Evaluation of an indirect serum ELISA and a bacteriological faecal culture test
      for diagnosis of Salmonella serotype Dublin in cattle using latent class models.
AB  - AIMS: To evaluate a conventional bacteriological test based on faecal culture and
      an indirect serum ELISA for detection of S. Dublin infected cattle. To compare
      the predictive values of the two tests in relation to the prevalence. METHODS AND
      RESULTS: A total of 4531 paired samples from cattle in 29 dairy herds were
      analysed for presence of S. Dublin bacteria in faeces and immunoglobulins
      directed against S. Dublin lipopolysaccharide in an indirect serum ELISA.
      Sensitivity and specificity were estimated at two ELISA cut-off values using a
      validation method based on latent class models, which presumably provides less
      biased results than traditional validation methods. Stratification of data into
      three age groups gave significantly better estimates of test performance of the
      ELISA. Receiver operating characteristic (ROC) curves were constructed for
      comparison of overall performance of the ELISA between the three age groups. The
      sensitivity of the faecal culture test was low (6-14%). ELISA appeared to have a
      higher validity for animals aged 100-299 days of age than older or younger
      animals. Overall, the negative predictive value of the ELISA was 2-10 times
      higher than for the faecal culture test at realistic prevalence of infection in
      the test population. CONCLUSIONS: The diagnostic sensitivity of the faecal
      culture test for detection of S. Dublin is poor, the specificity is 1. The
      superior sensitivity and negative predictive value of the serum ELISA makes this
      test preferable to faecal culture as an initial screening test and for
      certification of herds not infected with S. Dublin. SIGNIFICANCE AND IMPACT OF
      THE STUDY: A quantitative estimate of the sensitivity of a faecal culture test
      for S. Dublin in a general population was provided. ELISA was shown to be an
      appropriate alternative diagnostic test. Preferably, samples from animals aged
      100-299 days of age should be used as these give the best overall performance of
      the ELISA. Plots of ROC curves and predictive values in relation to prevalence
      facilitates optimisation of the ELISA cut-off value.

PMID- 14723693
TI  - Newly isolated Bacillus clausii GMBAE 42: an alkaline protease producer capable
      to grow under higly alkaline conditions.
AB  - AIMS: The isolation and identification of new Bacillus sp. capable of growing
      under highly alkaline conditions as alkaline protease producers. METHODS AND
      RESULTS: A Bacillus strain capable of growing under highly alkaline conditions
      was isolated from compost. The strain is a Gram-positive, spore-forming, motile,
      aerobic, catalase- and oxidase-positive, alkaliphilic bacterium and designated as
      GMBAE 42. Good growth of the strain was observed at pH 10. The strain was
      identified as Bacillus clausii according to the physiological properties,
      cellular fatty acid composition, G + C content of genomic DNA and 16S rRNA gene
      sequence analyses. The result of 16S rRNA sequence analyses placed this bacterium
      in a cluster with B. clausii. The G + C content of the genomic DNA of the isolate
      GMBAE 42 was found to be 49 mol%. The crude extracellular alkaline protease
      produced by the isolate showed maximal activity at pH 11.0 and 60 degrees C.
      CONCLUSIONS: The results suggest that isolated strain GMBAE 42 is a new type of
      B. clausii capable of growing at pH 10.0 and produce extracellular alkaline
      protease very active at pH 11.0. SIGNIFICANCE AND IMPACT OF THE STUDY: Isolated
      strain could be used in commercial alkaline protease production and its enzyme
      can be considered as a candidate as an additive for commercial detergents.

PMID- 14723694
TI  - The rapid identification of Acinetobacter species using Fourier transform
      infrared spectroscopy.
AB  - AIMS: Fourier transform infrared (FT-IR) was used to analyse a selection of
      Acinetobacter isolates in order to determine if this approach could discriminate
      readily between the known genomic species of this genus and environmental
      isolates from activated sludge. METHODS AND RESULTS: FT-IR spectroscopy is a
      rapid whole-organism fingerprinting method, typically taking only 10 s per
      sample, and generates 'holistic' biochemical profiles (or 'fingerprints') from
      biological materials. The cluster analysis produced by FT-IR was compared with
      previous polyphasic taxonomic studies on these isolates and with 16S-23S rDNA
      intergenic spacer region (ISR) fingerprinting presented in this paper. FT-IR and
      16S-23S rDNA ISR analyses together indicate that some of the Acinetobacter
      genomic species are particularly heterogeneous and poorly defined, making
      characterization of the unknown environmental isolates with the genomic species
      difficult. CONCLUSIONS: Whilst the characterization of the isolates from
      activated sludge revealed by FT-IR and 16S-23S rDNA ISR were not directly
      comparable, the dendrogram produced from FT-IR data did correlate well with the
      outcomes of the other polyphasic taxonomic work. SIGNIFICANCE AND IMPACT OF THE
      STUDY: We believe it would be advantageous to pursue this approach further and
      establish a comprehensive database of taxonomically well-defined Acinetobacter
      species to aid the identification of unknown strains. In this instance, FT-IR may
      provide the rapid identification method eagerly sought for the routine
      identification of Acinetobacter isolates from a wide range of environmental
      sources.

PMID- 14723695
TI  - Characterization of three Lactobacillus delbrueckii subsp. bulgaricus phages and
      the physicochemical analysis of phage adsorption.
AB  - AIMS: Three indigenous Lactobacillus delbrueckii subsp. bulgaricus bacteriophages
      and their adsorption process were characterized. METHODS AND RESULTS: Phages
      belonged to Bradley's group B or the Siphoviridae family (morphotype B1). They
      showed low burst size and short latent periods. A remarkably high sensitivity to
      pH was also demonstrated. Indigenous phage genomes were linear and double
      stranded DNA molecules of approx. 31-34 kbp, with distinctive restriction
      patterns. Only one phage genome appeared to contain cohesive ends. Calcium ions
      did not influence phage adsorption, but it was necessary to accelerate cell lysis
      and improve plaque formation. The adsorption kinetics were similar on viable and
      nonviable cells, and the adsorption rates were high between 0 and 50 degrees C.
      SDS and proteinase K treatments did not influence the phage adsorption but
      mutanolysin and TCA reduced it appreciably. No significant inhibitory effect on
      phage adsorption was observed for the saccharides tested. This study also
      revealed the irreversibility of phage adsorption to their hosts. CONCLUSIONS,
      SIGNIFICANCE AND IMPACT OF THE STUDY: The study increases the knowledge on phages
      of thermophilic lactic acid bacteria.

PMID- 14723696
TI  - A potent feed preservative candidate produced by Calcarisporium sp., an endophyte
      residing in stargrass (Cynodon dactylon).
AB  - AIMS: The cultures of an endophytic fungus Calcarisporium sp. were screened for
      inhibitors on the growth of feed-associated moulds and on the aflatoxin
      biosynthesis to find a safe and effective feed preservative. METHODS AND RESULTS:
      Eight test fungi were isolated from the spoiled poultry feed. The endophytic
      fungus Calcarisporium sp. was separated from the Chinese coastal grass Cynodon
      dactylon. The antifungal action concerning the endophytic culture extract (ECE)
      was performed with propionic acid (PPA) as the corresponding reference. The ECE
      had a similar antifungal efficacy to PPA in a concentration-dependent manner. The
      susceptibility order of the ECE to the test fungi was found to be Fusarium sp. >
      Aspergillus spp. > Penicillium spp. Furthermore, the application of the ECE in
      pelleted-layer duck feed as a preservative was carried out at a humidity of 10,
      15 and 20%. It has been discerned that mould growth and aflatoxin biosynthesis
      could be co-inhibited almost completely by ECE at concentrations higher than 1.0%
      (w/w). The LD50 of the ECE on mice was shown to be higher than 28 g kg-1.
      CONCLUSIONS: The ECE can be selected as an inhibitor to preserve poultry feed on
      inhibiting the growth of mould and aflatoxin biosynthesis during feed storage.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The ECE may be an effective and biosafe
      antifungal ingredient for poultry feed and holds a potential market prospect in
      feed industry.

PMID- 14723697
TI  - Induction of viable but nonculturable state in Vibrio parahaemolyticus and its
      susceptibility to environmental stresses.
AB  - AIMS: This work analysed factors that influence the induction of viable but
      nonculturable (VBNC) state in the common enteric pathogen, Vibrio
      parahaemolyticus. The susceptibility of the VBNC cells to environmental stresses
      was investigated. METHODS AND RESULTS: Bacterium was cultured in tryptic soy
      broth-3% NaCl medium, shifted to a nutrient-free Morita mineral salt-0.5% NaCl
      medium (pH 7.8) and further incubated at 4 degrees C in a static state to induce
      the VBNC state in 28-35 days. The culturability and viability of the cells were
      monitored by the plate count method and the Bac Light viable count method,
      respectively. Cells grown at the optimum growth temperature and in the
      exponential phase better induced the VBNC state than those grown at low
      temperature and in the stationary phase. Low salinity of the medium crucially and
      markedly shortened the induction period. The VBNC cells were highly resistant to
      thermal (42, 47 degrees C), low salinity (0% NaCl), or acid (pH 4.0)
      inactivation. CONCLUSIONS: Optimal conditions for inducing VBNC V.
      parahaemolyticus were reported. The increase in resistance of VBNC V.
      parahaemolyticus to thermal, low salinity and acidic inactivation verified that
      this state is entered as part of a survival strategy in an adverse environment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The methods for inducing VBNC V.
      parahaemolyticus in a markedly short time will facilitate further physiological
      and pathological study. The enhanced stress resistance of the VBNC cells should
      attract attention to the increased risk presented by this pathogen in food.

PMID- 14723698
TI  - Identification and characterization of a conserved nuclease secreted by strains
      of the Lactobacillus casei group.
AB  - AIMS: Nuclease secretion was evaluated for five species of Lactobacillus and the
      activity was characterized in terms of thermal resistance, molecular weight and
      mode of action on plasmid DNA. METHODS AND RESULTS: Assays of nuclease from L.
      rhamnosus ATCC 9595 on DNA of different origins indicates a broad activity
      spectrum. Secreted nuclease from this strain resists a thermal treatment of 20
      min at 100 degrees C, is not sensitive to a treatment for disruption of
      disulphide bonds nor to EDTA treatment under 10 mM l(-1). Nuclease production is
      not growth linked and seems to be constitutive. Extracellular nuclease of L.
      rhamnosus ATCC 9595 introduces a single-stranded nick in supercoiled DNA, thus
      potentially reducing the transformability of plasmid DNA. In seven of eight
      tested strains, SDS-PAGE revealed a major protein with a molecular weight of ca
      35 kDa. Minor degradation products also showed nuclease activity. CONCLUSIONS: A
      comparative analysis of the extracellular fractions of 14 different Lactobacillus
      strains indicate that nuclease secretion seems to be a widely distributed
      function among species of milk-related lactobacilli. The production of secreted
      nuclease may contribute to the low ability of Lactobacillus spp. to be
      transformed and maintain exogenous DNA. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Determination of the characteristics and distribution of nuclease activity
      contribute to developing strategies to overcome this barrier to efficient
      transformation of milk lactobacilli.

PMID- 14723699
TI  - A comparison of methods used to enumerate Escherichia coli in conventionally
      treated sewage sludge.
AB  - AIMS: This study examined the suitability of three analytical methods for
      isolating and enumerating Escherichia coli from conventionally treated sewage
      sludge. METHODS AND RESULTS: Crude sewage, mesophilic anaerobic digested (MAD)
      sludge, and final product sludge samples were taken from six sewage treatment
      works for analysis. Two of the three methods tested were membrane filtration
      techniques, utilizing chromogenic E. coli/coliform (CEC) media and membrane
      lactose glucuronide agar (MLGA); the third method was a most probable number
      (MPN) technique utilizing Colilert in Quantitray 2000 (Idexx). The methods were
      evaluated for variation, consistency, false-positive and false-negative results,
      as well as method correlation. The methods gave good and consistent recovery of
      E. coli for a range of conventionally treated sewage matrices. All of the methods
      had a false-positive rate of <3%, although MLGA had a high false-negative rate
      (35.5%) compared with Colilert (3.81%) and the CEC method (6.75%). This resulted
      in slightly lower presumptive counts but comparable numbers of confirmed counts.
      CONCLUSIONS: The three detection methods tested, chromogenic, MLGA and Colilert
      gave comparable recoveries, and did not vary by greater than one order of
      magnitude (1 log). SIGNIFICANCE AND IMPACT OF THE STUDY: Forthcoming revisions to
      the Use of Sludge in Agriculture Regulations (1989) will categorize sewage sludge
      as untreated, conventionally treated or enhanced treated in accordance to
      microbiological standards. The standard will be based upon numbers of E. coli
      removed through the sludge treatment process and the numbers remaining in the
      final product. It is recommended that the Colilert 2000 (Idexx, Westbrook, Maine)
      and CEC methods would be equally suitable to assess the reduction of indigenous
      E. coli in conventionally treated sludges, and that MLGA be used with follow-up
      confirmatory testing.

PMID- 14723700
TI  - Microbiological characterization and probiotic potential of koko and koko sour
      water, African spontaneously fermented millet porridge and drink.
AB  - AIMS: To identify and examine the diversity of predominant lactic acid bacteria
      (LAB) in koko and koko sour water (KSW) from different Ghanaian production sites
      with regard to pattern of fermentation (API 50 CHL), genotype, antimicrobial
      activity, and resistance to low pH and bile salts. METHODS AND RESULTS: In total
      215 LAB were isolated from koko and KSW. The isolates were identified using
      intergenic transcribed spacers (ITS)-PCR restriction fragment length polymorphism
      (RFLP), API 50 CHL, restriction enzyme analysis with pulsed-field gel
      electrophoresis (REA-PFGE) and sequencing of the 16S rRNA gene. The dominating
      micro-organisms in koko was found to be Weisella confusa and Lactobacillus
      fermentum, followed by Lact. salivarius and Pediococcus spp. Chemometric data
      analysis were used to link the LAB species to the different production stages and
      production sites. At intra-species level the isolates were found to have a great
      diversity. The isolates were investigated for antimicrobial activity using agar
      diffusion assays, and acid and bile tolerance. Most isolates showed low levels of
      antimicrobial activity towards the indicator strain Listeria innocua, but not
      towards the bacteriocin-sensitive Lact. sakei. Growth of all LAB isolates was
      unaffected by the presence of 0.3% (v/v) oxgall bile. The isolates were able to
      survive, but were not able to grow in growth medium adjusted to pH 2.5.
      CONCLUSIONS: The dominating LAB of koko and KSW were W. confusa and Lact.
      fermentum showing a pronounced taxonomic biodiversity at sub-species level
      between stages within the production as well as between production sites. Other
      species observed in KSW were Lact. salivarius, Ped. pentosaceus, Ped.
      acidilactici and Lact. paraplantarum. They occurred in levels of 108 CFU ml-1 in
      fresh KSW and showed uniform antimicrobial activity, and acid and bile tolerance.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present study gives a detailed picture
      of the taxonomy and diversity of LAB in an African-fermented millet product that
      may have potential as a probiotic product for the local population. The
      chemometric tools Principal Component Analysis and anova Partial Least Squares
      Regression were proven to be useful in the analysis of microbial groupings and
      associations with specific sites and stages in the production of koko and KSW.

PMID- 14723701
TI  - Effects of high-pressure processing on Listeria monocytogenes, spoilage
      microflora and multiple compound quality indices in chilled cold-smoked salmon.
AB  - AIMS: To evaluate the effect of high-pressure processing (HPP) on Listeria
      monocytogenes, microbial and chemical changes and shelf-life in chilled cold
      smoked salmon (CSS). METHODS AND RESULTS: First, challenge tests with L.
      monocytogenes were carried out using HPP of the product at 0.1 (control), 150,
      200 and 250 MPa. Secondly, storage trials with the naturally contaminated product
      and HPP at 0.1 (control) and 200 MPa were realized. Shelf-life, microbial changes
      and chemical changes were determined and existing predictive models and multiple
      compound quality indices evaluated. HPP with 250 MPa did not inactivate L.
      monocytogenes but significant lag phases of 17 and 10 days were observed at ca 5
      and 10 degrees C, respectively. HPP with 200 MPa had a marked effect on both
      colour and texture of CSS. CONCLUSIONS: High-pressure processing was unable to
      prevent growth of L. monocytogenes or spoilage of chilled CSS. Existing
      mathematical models allowed growth rates of L. monocytogenes and shelf-life of
      samples without high-pressure treatments to be predicted. SIGNIFICANCE AND IMPACT
      OF THE STUDY: High-pressure processing seems more appropriate for new types of
      salmon products than for a classical product like CSS where consumers expect
      specific quality attributes.

PMID- 14723702
TI  - Determination of Cryptosporidium parvum oocyst viability by fluorescence in situ
      hybridization using a ribosomal RNA-directed probe.
AB  - AIMS: Fluorescence in situ hybridization (FISH) has been proposed for species
      specific detection, and viability determination of Cryptosporidium parvum
      oocysts. FISH-based viability determination depends on rRNA decay after loss of
      viability. We examined the effects of RNase(s) and RNase inhibitors on FISH of C.
      parvum. METHODS AND RESULTS: FISH was performed using a 5'-Texas red-labelled DNA
      oligonucleotide probe at 1 pM microl(-1). Intact and heat-permeabilized oocysts
      were treated with 1-100 microg ml(-1) RNase. FISH of intact oocysts appeared
      unaffected by exogenous RNase if this was neutralized before permeabilization.
      FISH fluorescence of heat-killed oocysts stored in phosphate-buffered saline at
      room temperature decayed by 1/2 after 55 h, but remained detectable after 6 days.
      Addition of vanadyl ribonucleoside complex (VRC) extended rRNA half-life of heat
      permeabilized oocysts to 155 h. CONCLUSIONS: Extended rRNA half-life may result
      in viability overestimation using FISH. RNase pretreatment before FISH is
      recommended to destroy residual rRNA in recently killed oocysts. Incorporation of
      1-10 mM l(-1) VRC before FISH permeabilization steps should neutralize RNase
      activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Elimination of FISH fluorescence
      of nonviable C. parvum is desirable. Use of RNase and VRC is suggested to reduce
      numbers of false-positive 'viable' oocysts.

PMID- 14723703
TI  - Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter
      in astrocytes.
AB  - Sept2 is a member of the septin family of GTPases. Septins form filaments in a
      GTP-form dependent manner, and are involved in cytokinesis from yeast to mammals;
      however, some mammalian septins, including Sept2, are expressed in the brain, a
      tissue in which almost all the cells are postmitotic. Recently, some functions of
      mammalian septin other than cytokinesis such as vesicle transport have been
      reported. However, mammalian septin's physiological functions are still unclear.
      The present study revealed that Sept2 co-localizes with the astrocyte glutamate
      transporter GLAST in the Bergmann glial processes facing axons and synapses.
      Biochemical analyses demonstrated that Sept2 bound directly to the carboxy
      terminal region of GLAST in a GDP-form dependent manner. Expression of
      constitutive GDP-form Sept2 mutant reduced the glutamate uptake activity of GLAST
      via internalization of GLAST from cell surface. Thus Sept2 may regulate GLAST
      mediated glutamate uptake by astrocytes, which is important for appropriate
      transmitter signalling in the cerebellum.

PMID- 14723704
TI  - CAST2: identification and characterization of a protein structurally related to
      the presynaptic cytomatrix protein CAST.
AB  - The cytomatrix at the active zone (CAZ) is thought to define the site of Ca2+
      dependent exocytosis of neurotransmitters. We have recently identified a novel
      CAZ protein from rat brain which we have named CAST (CAZ-associated structural
      protein). CAST forms a large molecular complex with other CAZ proteins such as
      Bassoon, RIM1 and Munc13-1, at least through direct binding to RIM1. Here, we
      have identified a rat protein that is structurally related to CAST and named it
      CAST2. Subcellular fractionation analysis of rat brain shows that CAST2 is also
      tightly associated with the postsynaptic density fraction. Like CAST, CAST2
      directly binds RIM1 and forms a hetero-oligomer with CAST. In primary cultured
      rat hippocampal neurones, CAST2 co-localizes with Bassoon at synapses.
      Furthermore, immunoelectron microscopy reveals that CAST2 localizes to the
      vicinity of the presynaptic membrane of synapses in mouse brain. Sequence
      analysis reveals that CAST2 is a rat orthologue of the human protein ELKS. ELKS
      has also recently been identified as Rab6IP2 and ERC1. Accordingly, the original
      CAST is tentatively re-named CAST1. These results indicate that CAST2 is a new
      component of the CAZ and, together with CAST1, may be involved in the formation
      of the CAZ structure.

PMID- 14723705
TI  - A PLCdelta1-binding protein, p122/RhoGAP, is localized in caveolin-enriched
      membrane domains and regulates caveolin internalization.
AB  - A GTPase activating protein (GAP), p122, has previously been cloned as a
      phospholipase C (PLC)delta1-interacting protein. p122 shows a specific GAP
      activity for Rho and enhances the enzyme activity of PLCdelta1. In this study, we
      examined the localization and functions of p122/RhoGAP, using enhanced green
      fluorescent protein (EGFP)-tagged proteins. EGFP-p122 was observed as punctate
      structures at the plasma membrane of BHK (fibroblastic) cells and MDCK
      (epithelial) cells. This patchy distribution depended on membrane cholesterol
      levels and the C-terminal region of p122 containing the GAP domain was
      responsible for it. Sucrose density gradient centrifugation and immunostaining of
      caveolin-1 revealed that p122 was localized in caveolin-enriched membrane domains
      mainly via its GAP domain. We demonstrated that transient expression of EGFP-p122
      caused internalization of caveolin-1. Moreover, when the EGFP-tagged GAP domain
      was introduced in another fibroblastic cell line, NRK cells, punctate fluorescent
      structures were co-localized with caveolin-1. In this case, caveolin-1-positive
      structures were found in patches of F-actin, unlike those of untransfected cells
      that formed linear arrays along with actin stress fibres. These results suggest
      that p122 is localized in caveolae and plays an important role in caveolin
      distribution through reorganization of the actin cytoskeleton.

PMID- 14723706
TI  - Mechanisms for the control of body size by a G-kinase and a downstream TGFbeta
      signal pathway in Caenorhabditis elegans.
AB  - We recently showed that egl-4 mutants in Caenorhabditis elegans have a much
      larger body size and that the egl-4 gene encodes cyclic GMP-dependent protein
      kinases (G-kinases). Cell sizes, but not cell numbers, in the major organs are
      increased in the mutants. Genetic interaction studies suggest that EGL-4
      represses the DBL-1/TGFbeta pathway that is known to control body size. To
      understand the mechanisms of body size control in C. elegans, we analysed sma-2,
      sma-4 and sma-6 small mutants in the DBL-1 pathway. The volumes of major organs
      were precisely determined with the method developed by us. They are significantly
      decreased as compared to those of the wild-type while cell numbers are not,
      indicating that cell size is decreased. DNA contents in the nuclei of major
      organs are not significantly changed in the small mutants and in an egl-4 large
      mutant. Total protein contents are much decreased in the small mutants and
      slightly increased in the egl-4 mutant. Based on these results, we propose that
      decreased cell and body size of the small mutants in the DBL-1/TGFbeta pathway is
      mainly due to decreased levels of protein expression, and that increase in fluid
      content is a major reason for the increase in cell and body size in egl-4
      mutants.

PMID- 14723707
TI  - The G12 family of heterotrimeric G proteins and Rho GTPase mediate Sonic hedgehog
      signalling.
AB  - Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision,
      cellular proliferation, and patterning during vertebrate development. The
      intracellular Shh signalling is transduced by Smoothened (Smo), a seven
      transmembrane spanning protein that belongs to the G-protein coupled receptor
      family. Among four families of Galpha subunits, Galphai has been thought to be
      responsible for transducing Shh signalling, while several lines of evidence
      indicated that other signalling pathways may be involved. We found that the G12
      family of heterotrimeric G proteins and the small GTPase RhoA are involved in
      Shh/Smo-mediated cellular responses, including stimulation of target gene
      promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also
      found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of
      GLI3 which is thought to transduce Shh signals to nucleus. Furthermore,
      misexpression of a G12-specific GTPase-activating protein in rat neural tubes
      leads to pertubation of motor neurone and interneurone development, mimicking the
      effects of decreased Shh signalling. These results show that Shh signalling is
      mediated in part by activating G12 family coupled signalling pathways. The
      participation of RhoA, a pivotal molecular switch in many signal transduction
      pathways, may help explain how Shh can trigger a variety of cellular responses.

PMID- 14723708
TI  - TNFalpha-induced ATF3 expression is bidirectionally regulated by the JNK and ERK
      pathways in vascular endothelial cells.
AB  - ATF3 (Activating transcription factor 3), a member of the CREB/ATF family, can be
      induced by stress and growth factors in mammalian cells, and is thought to play
      an important role in the cardiovascular system. However, little is currently
      known about how the induction of ATF3 is regulated, except that the JNK pathway
      is involved. Here, we investigated the differential roles of the MAPK pathways
      involved in TNFalpha (tumour necrosis factor alpha)-induced ATF3 expression in
      vascular endothelial cells. In human umbilical vein endothelial cells, the
      expression of constitutively active MKK7 (MAPK kinase 7) increased the number of
      ATF3-positive cells, and dominant negative MKK7 suppressed the TNFalpha-induced
      expression of ATF3, indicating a requirement for the JNK pathway. In contrast,
      the expression of constitutively active or dominant negative MEK1/2 (MAPK/ERK
      kinase 1/2) suppressed or enhanced TNFalpha-mediated induction of ATF3,
      respectively. In support of this, the MEK1/2 specific inhibitor U0126 enhanced
      the expression of ATF3 induced by TNFalpha. Furthermore, the ERK pathway inhibits
      the TNFalpha-mediated induction of ATF3 mRNA, but not its stability, suggesting
      the involvement of ERK activity in the transcriptional regulation of the ATF3
      gene. Our results suggest that TNFalpha-induced ATF3 gene expression is
      bidirectionally regulated by the JNK and ERK pathways in vascular endothelial
      cells.

PMID- 14723709
TI  - Pmr1, a P-type ATPase, and Pdt1, an Nramp homologue, cooperatively regulate cell
      morphogenesis in fission yeast: the importance of Mn2+ homeostasis.
AB  - Schizosaccharomyces pombe pmr1+ gene is homologous to Saccharomyces cerevisiae
      PMR1 gene, which encodes the P-type Ca2+/Mn2+-ATPase. Addition of Mn2+, as well
      as Ca2+, to the medium induced pmr1+ gene expression in a calcineurin-dependent
      manner. The pmr1 knockout (Deltapmr1) cells exhibited hypersensitivity to EGTA. A
      screen for high gene dosage-suppressors of the EGTA-hypersensitive phenotype of
      Deltapmr1 led to the identification of pdt1+ gene, which encodes an Nramp-related
      metal transporter. The Deltapmr1 cells showed round cell morphology. Although
      Deltapdt1 cells appeared normal in the regular medium, it showed round cell
      morphology similar to that of the Deltapmr1 cells when Mn2+ was removed from the
      medium. The removal of Mn2+ also exacerbated the round morphology of the
      Deltapmr1 cells. The Deltapmr1Deltapdt1 double mutants grew very slowly and
      showed extremely aberrant cell morphology with round, enlarged and depolarized
      shape. The addition of Mn2+, but not Ca2+, to the medium completely suppressed
      the morphological defects, while both Mn2+ and Ca2+ markedly improved the slow
      growth of the double mutants. These results suggest that Pmr1 and Pdt1
      cooperatively regulate cell morphogenesis through the control of Mn2+
      homeostasis, and that calcineurin functions as a Mn2+ sensor as well as a Mn2+
      homeostasis regulator.

PMID- 14723710
TI  - Pyostomatitis vegetans.
AB  - Pyostomatitis vegetans is a rare oral disorder often associated with
      gastrointestinal and/or cutaneous diseases and sometimes with other disorders.
      The association of pyostomatitis vegetans with inflammatory bowel disease,
      particularly ulcerative colitis, is well known and in most cases bowel disease
      precedes the onset of oral lesions by months or years. A peripheral eosinophilia
      has been observed in most reported cases. Pyostomatitis vegetans is characterized
      by erythematous, thickened oral mucosa with multiple pustules and superficial
      erosions. Histopathologically, it is characterized by intraepithelial and/or
      subepithelial abscesses containing large numbers of eosinophils. The pathogenesis
      is as yet unknown although immunological and microbial factors have been
      suggested as possible aetiological factors. Management of pyostomatitis vegetans
      consists mainly of immunosuppression using topical or systemic corticosteroids
      with medical and/or surgical treatment of any underlying inflammatory bowel
      disease.

PMID- 14723711
TI  - A new type of minocycline-induced cutaneous hyperpigmentation.
AB  - Pigmentary disorders are recognized adverse effects of the semi-synthetic
      tetracycline derivative antibiotic, minocycline. Three distinct types of
      minocycline-induced cutaneous pigmentation have been described. Type I, blue
      black pigmentation confined to sites of scarring or inflammation on the face;
      Type II, blue-grey circumscribed pigmentation of normal skin of the lower legs
      and forearms; and Type III, diffuse muddy brown pigmentation of normal skin
      accentuated in sun-exposed areas. We report two patients with acne vulgaris with
      a fourth type of minocycline-induced cutaneous pigmentation. They presented with
      circumscribed blue-grey pigmentation within acne scars confined to the back.
      Histology showed pigment within dendritic cells, and extracellularly throughout
      the dermis. Histochemistry identified a calcium containing melanin-like
      substance. Iron was absent. Immunohistochemistry confirmed some pigment
      containing cells to be macrophages. Electron microscopy demonstrated electron
      dense granules, free and membrane-bound, within macrophages and fibroblast-like
      cells. Energy-dispersive X-ray analysis confirmed the presence of calcium. Iron
      was absent. This fourth type of cutaneous minocycline hyperpigmentation may be a
      variant of Type I, but based on clinical, pathological and microanalytical
      differences, appears to be a new entity. The pigment may be a drug metabolite
      protein complex chelated with calcium, or an insoluble minocycline-melanin
      complex. We propose a classification of cutaneous minocycline pigmentation based
      on clinico-pathological criteria.

PMID- 14723712
TI  - Topical imiquimod immunotherapy in the management of lentigo maligna.
AB  - Melanoma in situ of the lentigo maligna (LM) type is a precursor lesion of LM
      melanoma. It most commonly occurs in elderly individuals, on the head and neck.
      Although surgical excision is recommended, this may not be practical for large
      lesions at cosmetically sensitive sites. In addition, histological changes
      commonly extend beyond the clinical margins of the lesion. This study describes
      the use of imiquimod 5% cream as topical immunotherapy in the management of
      lentigo maligna. Twelve patients (average age 63 years, 10 female), of biopsy
      proven facial LM were treated with topical imiquimod, three times a week for 6
      weeks. In the absence of an inflammatory response, patients were asked to apply
      the treatment daily. Seven showed clearance of the LM clinically and
      histologically. A further three patients showed clearance histologically with
      persisting pigmentation due to dermal melanin and melanophages. Thus, 10 of 12
      patients cleared with no relapse after a median follow-up of 6 months. Two
      patients failed to respond to imiquimod and their lesions were treated with
      surgical excision. Imiquimod was well tolerated, except in three patients who
      experienced an intense inflammatory response. Two of these also developed
      secondary infection. Imiquimod 5% cream appears to offer a potential noninvasive
      method for the treatment of lentigo maligna.

PMID- 14723713
TI  - Rowell's syndrome and associated antiphospholipid syndrome.
AB  - We report a 27-year-old primigravida with systemic lupus erythematosus, erythema
      multiforme-like lesions and a peculiar immunological pattern consisting of
      antinuclear antibody (speckled pattern) and rheumatoid factor, an association
      known as Rowell's syndrome. She also had a probable antiphospholipid syndrome as
      evidenced by the presence of a prolonged activated partial thromboplastin time,
      kaolin clotting time and thrombocytopenia.

PMID- 14723714
TI  - Does solitary morphoea profunda progress?
AB  - Solitary morphoea profunda (SMP) is an unusual form of scleroderma and is rarely
      mentioned in the literature. The back of the trunk is described as the commonest
      site of involvement by SMP. This disease has been recognized as a nonprogressive
      condition. We report three cases of SMP seen at our department within a 1-year
      period. Interestingly, all three patients were females and the lesions were
      situated on the right upper buttock. In one patient the lesion extended despite
      using topical tacrolimus but subsequently the lesion was kept under control with
      topical clobetasol propionate.

PMID- 14723715
TI  - Skin metastasis from nasopharyngeal carcinoma in four Chinese patients.
AB  - Nasopharyngeal carcinoma (NPC) is a common malignancy among southern Chinese. The
      tumours are mostly undifferentiated carcinomas and are associated with Epstein
      Barr virus. Patients present with a blood-stained postnasal discharge, impaired
      hearing, tinnitus or cervical lymph node enlargement. Radiotherapy with or
      without chemotherapy is the standard treatment. Though metastatic lung, bone or
      liver disease is not uncommon on relapse, skin metastasis is rarely reported. The
      small number of reports in the literature are either brief or have only a few
      patients. In this report, we describe our series of four Hong Kong Chinese
      patients with NPC who had distant cutaneous metastases.

PMID- 14723716
TI  - Miliaria crystallina in an intensive care setting.
AB  - Drop-like, transient blisters of miliaria crystallina may develop with focal
      intensity of heat within the skin, such as occurs in tropical climates or during
      febrile episodes. Miliaria crystallina develops due to a transient poral closure
      of the sweat duct opening, resulting in obstruction of free flow of eccrine sweat
      and retention in a vesicle below the skin surface. Dual cholinergic and
      adrenergic sweat gland innervation is influenced by a variety of medications used
      in intensive care patients. We present two febrile intensive care patients in
      whom enhanced alpha-adrenergic stimulation of sweat gland myoepithelia may have
      led to miliaria crystallina.

PMID- 14723717
TI  - Warfarin skin necrosis associated with protein S deficiency and a mutation in the
      methylenetetrahydrofolate reductase gene.
AB  - The use of warfarin is rarely complicated by skin necrosis. We describe a 50-year
      old woman who presented with a left leg deep venous thrombosis and subsequent
      pulmonary embolism. She was initially anticoagulated with low-molecular weight
      heparin and subsequently warfarin. Within 4 days abdominal skin necrosis
      developed. Investigations revealed the presence of protein S deficiency and in
      addition, a mutation in the methylenetetrahydrofolate reductase gene (MTHFR). We
      present, to our best knowledge, the first case of warfarin skin necrosis
      associated with a methylenetetrahydrofolate reductase mutation.

PMID- 14723718
TI  - Darier's disease restricted to sun-exposed areas.
AB  - We report a sporadic case of Darier's disease restricted to sun-exposed areas in
      a 17-year-old Japanese girl. There are several clinical variants of Darier's
      disease including unilateral Darier's disease, localized Darier's disease,
      segmental Darier's disease, and acral Darier's disease, but few cases of Darier's
      disease restricted to sun-exposed areas have been described in the literature.
      Although it remains controversial whether UV irradiation can evoke the eruption
      of Darier's disease or not, cases of Darier's disease restricted to sun-exposed
      areas like our case may help to further clarify the relationship between Darier's
      disease, UV irradiation and photo-exacerbation of this autosomal dominant
      genodermatosis.

PMID- 14723719
TI  - Giant recurrent pyogenic granuloma on the face with satellitosis responsive to
      systemic steroids.
AB  - Pyogenic granuloma is a common benign skin tumour. However, giant recurrent
      pyogenic granuloma with satellitosis is relatively rare. We present a 52-year-old
      man who had recurrent gigantic pyogenic granuloma with satellitosis responsive to
      systemic steroids. Our case of recurrent pyogenic granuloma is interesting
      because of its clinical presentation, recurrence following surgical excision and
      its steroid responsiveness. Systemic steroids may be effective in treating
      recurrent giant pyogenic granulomas during their high-proliferation phase.

PMID- 14723720
TI  - Photodynamic therapy may be useful in debulking cutaneous lymphoma prior to
      radiotherapy.
AB  - Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (5-ALA) is a
      promising new treatment for superficial malignant nonmelanoma tumours, including
      cutaneous malignant lymphoma. Here, we report a case of cutaneous anaplastic
      large cell lymphoma effectively treated by PDT with topical 5-ALA in combination
      with radiotherapy.

PMID- 14723721
TI  - Arsenic-induced keratoses and Bowen's disease.
AB  - We report a patient with arsenic-induced keratoses and Bowen's disease. Chronic
      arsenicism may lead to both cutaneous and systemic neoplasms and patients should
      undergo regular long-term examination. Our patient had widespread cutaneous
      disease, which responded well to acitretin.

PMID- 14723722
TI  - Classical juvenile pityriasis rubra pilaris in a patient with Down syndrome.
AB  - We report a case of classical juvenile pityriasis rubra pilaris (CJPRP) in a 15
      year-old boy with Down syndrome. The rash was extensive, severe, accompanied by
      intense itching and responded to low-dose etretinate. Xerosis and cheilitis were
      also present, suggesting that keratinization defects associated with Down
      syndrome may be involved in the pathogenesis of CJPRP. PRP is a rare
      dermatological disorder and to the best of our knowledge, this is the first
      reported case of CJPRP in a patient with Down syndrome.

PMID- 14723723
TI  - The role of extracellular matrix protein 1 in human skin.
AB  - Extracellular matrix protein 1 (ECM1) was first identified in 1994 as an 85-kDa
      glycoprotein secreted by a mouse osteogenic stromal cell line. Subsequently, the
      human homologue has been found to regulate endochondral bone formation, and to
      stimulate proliferation of endothelial cells and induce angiogenesis. However, a
      role for ECM1 in skin physiology and homeostasis has also emerged. Specifically,
      in 2002, loss-of-function mutations in the ECM1 gene were discovered to be the
      cause of the rare autosomal recessive genodermatosis, lipoid proteinosis. This
      inherited disorder is characterized clinically by skin and mucosal infiltration
      and scarring and histologically by disruption/duplication of basement membrane
      and widespread deposition of hyaline material in the dermis. Moreover, other
      recent studies have identified circulating autoantibodies against the ECM1
      protein in most patients with lichen sclerosus, a common chronic inflammatory
      condition that shares some clinicopathological features with lipoid proteinosis.
      ECM1 thus serves as a target antigen in both an inherited and an acquired skin
      disorder. Within the epidermis, ECM1 has a role in the control of keratinocyte
      differentiation. Within the dermis, ECM1 binds to the major heparan sulphate
      proteoglycan, perlecan. In this way, ECM1 may act as a "biological glue" in the
      dermis, helping to regulate basement membrane and interstitial collagen fibril
      macro-assembly and growth factor binding. ECM1 may also have a role in other
      acquired skin disorders and physiological skin changes including scarring, wound
      healing and skin ageing, although this remains to be determined.

PMID- 14723724
TI  - Metallothionein-null mice exhibit reduced tolerance to ultraviolet B injury in
      vivo.
AB  - Events that induce expression of the metallothionein (MT) gene, such as injection
      of cadmium chloride, cold stress or topical application of 1,25-dihydroxyvitamin
      D3, can deplete the number of ultraviolet (UV) B-induced sunburn cells (SBC) in
      mouse skin in vivo. MT-null mouse skin explants exhibit reduced tolerance to UVB
      injury in vitro. However, the in vivo response of MT-null mice to UVB injury has
      not been investigated. In the present study, we investigated the role of the MT
      gene on UVB injury in vivo. MT-null mice that are deficient in MT-I and MT-II
      genes were studied and compared with homozygous wild-type mice. Mouse dorsal skin
      was irradiated with 0.05, 0.70 and 1.40 J/cm2 UVB. The thickness of the dorsal
      skin was measured with a spring micrometer before and 24 h after UVB irradiation.
      In addition, SBC were counted 24 h after UVB irradiation. No significant
      difference was found in the change of skin thickness between MT-null mice and
      control mice irradiated with low-dose UVB (0.05 J/cm2) (Student's t-test, t =
      1.519, P = 0.167). At higher doses (0.70 and 1.40 J/cm2), the skin of MT-null
      mice became much thicker than that of control mice (Student's t-test, t = 6.576,
      P < 0.01 and t = 3.142, P = 0.007, respectively). More SBC were detected in MT
      null mice skin irradiated with the highest dose of UVB (1.40 J/cm2) (Student's t
      test, t = 4.258, P < 0.01). These results suggest that the MT gene in mice has a
      photoprotective role in vivo.

PMID- 14723725
TI  - Immunolocalization of target autoantigens in IgA pemphigus.
AB  - IgA pemphigus is a rare autoimmune bullous disease characterized by IgA
      deposition at keratinocyte cell surfaces. Clinically and histologically, IgA
      pemphigus is divided into two major subtypes: subcorneal pustular dermatosis
      (SPD) type and intraepidermal neutrophilic IgA dermatosis (IEN) type. Using cDNA
      transfection and living cell immunofluorescence, we previously showed that
      desmocollin 1, one of the desmosomal cadherins, is the autoantigen in SPD-type
      IgA pemphigus, but the autoantigen in IEN type is still unclear. In the present
      study we investigated antigen localization by postembedding immunoelectron
      microscopy. We examined three sera each of SPD-type and IEN-type IgA pemphigus.
      In SPD-type, gold particles were observed predominantly in the extracellular
      spaces between keratinocytes at desmosomes, although a few particles were
      observed in the intracellular domain at the desmosomal attachment plaques. In IEN
      type, the gold particles were observed mainly in the intercellular spaces in
      nondesmosomal areas. These results provide evidence that the IgA in the sera of
      SPD-type IgA pemphigus reacts with the extracellular domain of desmocollins. In
      contrast, the autoantigen for IEN type may in fact not be a component of
      desmosomes. IEN-type IgA pemphigus may be the first member of the pemphigus group
      of autoimmune bullous dermatoses that reacts with a nondesmosomal transmembranous
      protein.

PMID- 14723726
TI  - Changes in erythrocyte microrheology in patients with psoriasis.
AB  - Erythrocyte deformability (ED), the ability of red blood cells to change shape
      during flow in the microcirculation, is the basic rheological property of
      erythrocytes. It is determined by the surface area to volume ratio, viscoelastic
      properties of the membrane, and intracellular viscosity. The aim of the present
      study was to determine changes in erythrocyte microrheology in patients with
      psoriasis. The whole red cell deformability was measured by flow-channel
      diffractometry. To assess the contribution of different factors influencing
      changes in ED, measurements were also made of the biophysical state of the
      phospholipid bilayer, using an osmotic haemolysis technique, and internal
      viscosity, using electron paramagnetic resonance spectroscopy. The results showed
      a significant decrease in ED in patients with psoriasis in comparison with
      controls, and suggested that the main cause of this may be alterations in
      intracellular viscosity and membrane viscoelastic behaviour.

PMID- 14723727
TI  - Squamous metaplasia of Paget's disease.
AB  - A patient had triple extramammary Paget's disease of both axillary and genital
      regions. Right inguinal lymphadenopathy was found 1 year after excision of all
      the skin lesions. Excisional biopsy of the lymph node demonstrated a mixture of
      Paget cells and atypical squamoid cells with horn pearls suggestive of
      keratinization. The squamoid cells were positive for cytokeratin 10, a marker of
      suprabasal epidermis, and also positive for laminin gamma2 which is often
      expressed in invasive squamous cell carcinoma. The coexistence of these different
      cells within the same tumour island suggested that the squamoid cells derived
      from metaplasia of Paget cells.

PMID- 14723728
TI  - A new keratin 5 mutation (K199T) in a family with Weber-Cockayne epidermolysis
      bullosa simplex.
AB  - A new missense mutation in the keratin 5 gene (KRT5) in a Chinese family with
      Weber-Cockayne type epidermolysis bullosa simplex is reported. Direct sequencing
      identified a heterozygous A --> C substitution at nucleotide 596 altering codon
      199 of KRT5 from lysine to threonine in all affected family members, but not in
      the unaffected family members or in 50 unrelated control samples. The mutation is
      designated K199T. This mutated lysine residue is sited within the 1A domain of
      keratin 5 and is highly conserved among all type II keratins. The mutation may
      perturb the alignment of tonofilaments and, as a consequence, result in skin
      fragility and blistering.

PMID- 14723729
TI  - Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene.
AB  - Progressive osseous heteroplasia (OMIM 166350) is a rare autosomal dominant
      condition that presents in childhood as dermal ossification and may progress
      deeper to involve subcutaneous fat and connective tissue. Recently, paternally
      inherited inactivating mutations in the GNAS1 gene on chromosome 20q13 have been
      implicated in the pathogenesis, although sporadic cases have also been reported.
      We report a 9-year-old British Chinese girl with progressive osseous heteroplasia
      resulting from a de novo missense mutation (W281R) in the GNAS1 gene. She is of
      small stature (0.4th centile) and started to develop skin lesions at the age of 9
      months. These have been confirmed histologically as osteoma cutis. She is of
      normal intelligence and development and has no dysmorphic features. The GNAS1
      gene exhibits imprinting and maternally inherited mutations have previously been
      shown to result in Albright's hereditary osteodystrophy (OMIM 103580) with
      pseudohypothyroidism type 1a, whereas paternally inherited mutations result in
      progressive osseous heteroplasia or the Albright's hereditary osteodystrophy
      phenotype with pseudopseudohypothyroidism (OMIM 300800). With only nine mutations
      of the GNAS1 gene reported so far in progressive osseous heteroplasia, this new
      mutation helps to extend further the genotype-phenotype correlation.

PMID- 14723730
TI  - Do dermatology outpatients value a copy of the letter sent to their general
      practitioner? In what way and at what cost?
AB  - Dermatology services are largely outpatient based. Time for satisfactory patient
      communication is limited, with an average of around 15 min per new patient. The
      amount of new information that can be retained after verbal communication alone
      is limited during such consultations. One way to reinforce such information is to
      send patients a copy of the hospital specialist's letter to the general
      practitioner. Before advocating this unreservedly, it is important to explore the
      value patients attach to receiving such a letter and to estimate the cost of this
      practice. In order to explore patients' views of copy letters more fully, all
      patients attending dermatology outpatients at Queen's Medical Centre, Nottingham
      during a week in October 2001 were sent copy letters and later interviewed by
      telephone using a structured questionnaire that gathered information on content,
      usage, clarity and perceived usefulness. Direct costs were also calculated. Of 70
      patients invited to participate, 59 (85%) could be contacted by telephone at the
      2-week follow-up period. Of those 59 patients contacted by telephone,
      surprisingly only 46 (78%) had actually received a copy letter at 14 days post
      consultation. Of the 46 patients receiving a copy letter, 45 (98%) thought the
      information in the letter was consistent with their consultation; the letter was
      read a mean number of two times; nine patients (20%) understood most and 36 (78%)
      all of the letter; 25 (54%) found it useful and a further 21 (46%) found it very
      useful. Patients' views as to the value in receiving the letter included improved
      communication, recall and a sense of increased involvement in health care
      decisions. The direct total cost of sending a copy letter was 25.3 pence per
      patient. Consultants who participated in the exercise did not perceive any
      additional difficulties in implementing this practice. This small study found
      that 100% of patients receiving a copy letter found it useful. The fact that
      around one-fifth of patients did not receive such copy letters within 2 weeks as
      intended is worrying, and requires further investigation. Sending a copy letter
      involves a relatively trivial cost for a practice which patients view as a
      valuable resource.

PMID- 14723731
TI  - Prevalence of foot diseases in outpatients attending the Institute of
      Dermatology, Bangkok, Thailand.
AB  - Two thousand patients who visited the outpatient department at the Institute of
      Dermatology, Bangkok, were assessed for the presence of foot diseases by
      questionnaire and physical examination. Abnormalities were detected in 741
      individuals (37.1%). Nonfungal conditions were more prevalent (31.4%), mainly
      consisting of eczema (254 cases, 12.7%) and psoriasis (176 cases, 8.8%). Fungal
      disease was observed in 119 cases (6.0%). There were 76 cases (3.8%) with tinea
      pedis and 33 cases (1.7%) with onychomycosis. The identified organisms causing
      tinea pedis were 57.9% nondermatophyte moulds, 36.8% dermatophytes, and
      2.6%Candida spp. The corresponding organisms causing onychomycosis were 51.6%
      nondermatophyte moulds, 36.3% dermatophytes, and 6.0%Candida spp. Among
      nondermatophytes, Scytalidium dimidiatum was the leading pathogen while
      Trichophyton rubrum and T. mentagrophytes were the predominant dermatophytes
      identified. Diabetes mellitus, peripheral vascular disease and activities related
      to foot trauma were noted to be predisposing factors for onychomycosis. Footwear,
      particularly sandals and cut shoes, was the only factor relevant to individuals
      with tinea pedis (P < or = 0.05). In contrast with other published data on fungal
      foot infections, this study disclosed a higher prevalence of nondermatophyte
      organisms, predominantly S. dimidiatum, as the major cause of tinea pedis and
      onychomycosis. An increase in awareness is necessary to identify such cases,
      prevent misdiagnosis and initiate appropriate treatment.

PMID- 14723732
TI  - An elderly patient with mycosis fungoides successfully treated with chronic low
      dose oral etoposide therapy.

PMID- 14723733
TI  - Allergic contact dermatitis due to diclofenac applied with iontophoresis.

PMID- 14723734
TI  - Cutaneous hyperpigmentation during therapy with hydroxychloroquine.

PMID- 14723735
TI  - Acquired primary cold contact urticaria after Hymenoptera sting.

PMID- 14723736
TI  - Leucocytoclastic vasculitis and influenza immunization.

PMID- 14723737
TI  - Transverse leukonychia of the fingernail following proximal nail fold trauma.

PMID- 14723738
TI  - Congenital dermoid fistula of the anterior chest region.

PMID- 14723739
TI  - Narrow-band (TL-01) ultraviolet B phototherapy for chronic urticaria.

PMID- 14723740
TI  - A further case of non-ILVEN.

PMID- 14723741
TI  - Curriculum planning in dermatology.
AB  - Curriculum planners should familiarize themselves with the recommendations for
      medical education in the UK made by the Quality Assurance Agency and the General
      Medical Council. The dermatology curriculum must maximize undergraduate learning
      experiences in dermatology, but lengthy curricula lead to rote learning and do
      not promote understanding. The core dermatology curricula might be built around
      the clinical problems graduates are likely to encounter as preregistration house
      officers, but should also prepare students for their future careers in whatever
      specialty. Graduates should know when it might be appropriate to refer a patient
      to a dermatologist. Learning experiences in dermatology might be threaded into
      the curriculum at a number of stages and student-selected components might
      provide opportunities to explore dermatological topics in depth. The views of a
      broad constituency will give the core curriculum validity and consensus might be
      reached with the Delphi technique or by using multidisciplinary groups.
      Temptations to overload the curriculum should be resisted. Medical curricula
      should give students time to experience the art of medicine as well as to explore
      the science behind clinical practice.

PMID- 14723742
TI  - Suction blister device for separation of viable epidermis from dermis.

PMID- 14723744
TI  - Controversies and challenges in the modern management of uterine fibroids.

PMID- 14723745
TI  - Intrapartum ultrasound estimation of total bladder volume.
AB  - OBJECTIVE: To determine whether real-time ultrasound measurement of multiple
      linear dimensions of the bladder could be used to estimate total bladder volumes
      of women in labour. AIM: To create a simple reproducible formula using ultrasound
      techniques to help estimate total bladder volumes of women in labour. This may
      prevent unnecessary catheterisation and conversely, avoid failure to catheterise
      when indicated, thereby reducing the complications associated with
      catheterisation and bladder overdistension. DESIGN: Prospective, observational
      study of women in labour. SETTING: Delivery Suite, Obstetric Hospital, University
      College London Hospitals. POPULATION: Forty-nine women in labour recommended for
      catheterisation by their attending midwives. METHOD: A real-time ultrasound
      scanner was used to measure bladder diameters in two planes: transverse width and
      height, and sagittal width and height. A Foley's catheter was inserted and the
      bladder drained into a graduated bowl under sterile conditions. These values and
      urine volumes were recorded and a formula for detecting bladder volumes above 300
      mL was developed using linear regression methods and the Bland-Altman limits of
      agreement. MAIN OUTCOME MEASURE: Sensitivity and specificity of derived formulae
      in predicting bladder volume from ultrasound measurements. Correctly predicted
      volumes greater than 300 mL. RESULTS: Among the 49 women, 36 were nulliparous and
      13 were multiparous. All had full-term pregnancies with cephalic presentation and
      were in active labour with cervical dilatations ranging from 3 to 10 cm. There
      were no previous caesarean sections among the multiparous women. Thirty-nine
      women had epidural analgesia. Indications for catheterisation included a palpable
      bladder per abdomen, or the interval from last urine voided. The catheterised
      volumes ranged from 30 to 720 mL with a median of 150 mL. The new equation (0.68
      x h x d x w) had a sensitivity of 77% (95% CI 46-95%) and specificity of 86% (95%
      CI 71-95%) for detecting bladder volumes greater than 300 mL. In order to ensure
      that about 95% of women in need of catheterisation are detected, the above
      equation was improved using the Bland-Altman limits of agreement. The sensitivity
      of this final equation (1.74 x h x d x w) was 100% (95% CI 75-100%) and the
      specificity dropped to 36% (95% CI 21-54%). CONCLUSION: It is possible to use
      real-time ultrasound in estimation of total bladder volumes of women in labour.
      The implications are that all of those normally selected as being in need of
      catheterisation could be detected, while about a quarter of those women would
      avoid unnecessary catheterisation.

PMID- 14723746
TI  - Maternal ethnic origin and fetal nasal bones at 11-14 weeks of gestation.
AB  - OBJECTIVES: Failure to visualise the fetal nasal bones at 11-14 weeks of
      gestation is associated with a significant increase in the risk for trisomy 21.
      However, it is not known whether the ethnic origin of the mother has any effect
      on the fetal profile and the prevalence of this marker. DESIGN: Prospective
      study. SETTING: London Teaching Hospital. POPULATION: Four thousand and four
      hundred and ninety-two consecutive fetuses undergoing routine first trimester
      ultrasound scanning at 11-14 weeks of gestation in a multiethnic population.
      METHODS: Examination of the nasal bones was attempted in the fetuses. MAIN
      OUTCOME MEASURE: Rate of visualisation of the fetal nasal bones. RESULTS: Five
      hundred fetuses were excluded from the analysis because of chromosomal
      abnormalities or a technically unsatisfactory examination. In the remaining 3992
      fetuses, the maternal ethnic origin was African in 13.0%, Asian in 15.3% and
      Caucasian in 66.0%. Compared with Caucasians, the failure to visualise the fetal
      nasal bones was significantly higher in women of African (P= 0.0001) but not
      Asian origin (P= 0.24). A multivariable logistic regression model showed that
      having a mother of African origin is still significantly associated with an
      increased likelihood of absent fetal nasal bones compared with Caucasians (odds
      ratio 2.33), even after correcting for maternal age, parity and crown-rump
      length. CONCLUSION: There is a significant difference in the rate of
      visualisation of the fetal nasal bones in the first trimester in mothers of
      different ethnic origin. This suggest that corrections for maternal ethnicity
      will be required to ensure equity of fetal nasal bone screening in multiracial
      populations. Whether corrections are required for the father's ethnic origin
      remains to be determined.

PMID- 14723747
TI  - Ponderal index is a poor predictor of in utero growth retardation.
AB  - OBJECTIVE: To evaluate the usefulness of ponderal index (PI) and related indices
      of weight and length in identifying asymmetric growth, body thinness and organ
      asymmetry associated with IUGR. DESIGN: Cross sectional study. SETTING: Aberdeen
      Maternity Hospital. POPULATION: The population includes term (>/=37 weeks)
      singleton live births (n= 53,934) between 1986 and 1996, ultrasound measurements
      in 2522 pregnancies, 712 unselected term pregnancies in 1979/1980 and stillbirths
      (24-36 weeks) between 1986 and 1995 where the fetus was diagnosed as suffering
      from acute (n= 73) or chronic (n= 30) anoxic death. METHODS: The strength of
      association between direct measures of IUGR and various indices of weight and
      length was determined by linear and multiple stepwise linear regression. MAIN
      OUTCOME MEASURES: Weight, length, PI and skinfold thicknesses (triceps, biceps,
      flank thighs, back) were measured at birth. Abdominal circumference, biparietal
      diameter and femur length were measured by ultrasound at >/=37 weeks. Ratio of
      liver, heart and kidney to brain were measured in stillbirths. RESULTS: Weight
      alone was a better predictor of skinfold thickness, abdominal circumference and
      the ratio of abdominal circumference to biparietal diameter than weight divided
      by length raised to the power 1, 2, 3 (PI), 4 or 5. The inclusion of gestational
      age made little difference to the predictive ability of weight for these full
      term births. Weight, but not PI, was significantly different between the two
      groups of stillborn fetuses (chronic and acute), which had significantly
      different (P < 0.001) organ ratios. CONCLUSION: Body weight alone was a better
      predictor of anthropometric ratios, organ asymmetry and measures of thinness at
      birth thought to be associated with IUGR than the PI. The inclusion of a length
      term generally reduced the predictive ability with the highest powers resulting
      in the poorest prediction.

PMID- 14723748
TI  - ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women.
AB  - OBJECTIVE: To determine the effect of ONO-8815Ly on uterine contractions. DESIGN:
      A randomised, double-blind, placebo-controlled, dose-ascending, cross-over study.
      SETTING: Department of Obstetrics and Gynaecology, University Hospital of Lund,
      Sweden. POPULATION: Seventeen, healthy, parous and permanently sterilised women.
      METHODS: Intrauterine pressure was recorded on days 1-3 of bleeding of two
      menstruations. Subjects were intravenously treated with 4 or 8 microg/minute of
      ONO-8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin,
      50 pmol/kg body weight, were given 10 minutes before, during infusion after 60
      and 120 minutes and 60 minutes after completion of infusion. The plasma
      concentrations of ONO-8815Ly were measured in samples obtained immediately before
      each oxytocin injection. MAIN OUTCOME MEASURE: Area under pressure recording
      curve (AUC) 10 minutes before and after each oxytocin injection. RESULTS: Twelve
      women, six in each dose group, completed both recordings. Of these, two women of
      each group were not included in efficacy analysis due to non-responsiveness to
      oxytocin or missing baseline value. The AUC over 10 minutes before oxytocin
      injection after 60 minutes of infusion of ONO-8815Ly at 4 and 8 microg/minute was
      reduced to 21% and 37% of that before infusion, respectively. The AUC after
      oxytocin at that time amounted to 21% and 19%, respectively, of that before
      infusion. The activity and responsiveness remained low after 120 minutes but
      started to return to baseline 60 minutes after stopping infusion. Placebo had no
      effect. CONCLUSIONS: ONO-8815Ly is a potent inhibitor of spontaneous uterine
      contractility in non-pregnant women and it reduces the uterine response to
      oxytocin injections.

PMID- 14723749
TI  - An investigation into the association among preterm birth, cytokine gene
      polymorphisms and periodontal disease.
AB  - OBJECTIVE: To investigate a putative relationship between preterm delivery and
      the carriage of polymorphic genes that code for the cytokines interleukin-1beta
      (IL-1beta) at codon +3953 and tumour necrosis factor-alpha (TNF-alpha) at codon 
      308 in a group of postpartum women and to elucidate if the concurrent presence of
      periodontal disease increased the risk of preterm delivery in this group. DESIGN:
      Case-control study SETTING: Postnatal wards at Guy's and St Thomas' Hospital
      Trust. POPULATION: Postpartum women from southeast London, UK. METHODS: Case
      subjects were defined as those who experienced a birth at less than 37 weeks of
      gestation. Control subjects gave birth at term. Demographic data were collected
      and a periodontal examination was performed. Blood samples were collected and
      analysed by restriction fragment length polymerase techniques for the presence of
      each of the allelic variants. MAIN OUTCOME MEASURES: The level of periodontal
      disease and the carriage of allelic variants of IL-1beta+3953 and TNF-alpha-308
      genes. RESULTS: Forty-eight case subjects and 82 control subjects were assessed.
      There was no statistically significant difference in the carriage of the IL
      1beta+3953 allelic variant between cases and controls (29%versus 18%, P= 0.112).
      However, 23 (48%) of the case subjects and 24 (29%) of controls were heterozygous
      or homozygous for the variant TNF-alpha-308 gene (odds ratio [OR] 2.2, 95%
      confidence interval [CI] 1.0-5.0, P= 0.026). There was no association between the
      carriage of either the polymorphic IL-1beta+3953 or TNF-alpha-308 variant and the
      severity of periodontal disease. The combination of periodontal disease and the
      allelic variant did not increase the risk of preterm delivery. CONCLUSIONS: In
      this study, a higher proportion of women who delivered preterm carried the
      polymorphic TNF-alpha-308 gene. There did not appear to be any interaction
      between either of the genotypes and periodontal disease with preterm delivery as
      has been reported for bacterial vaginosis and the TNF-alpha-308 polymorphic gene.

PMID- 14723750
TI  - Women's perceptions of decision-making about hysterectomy.
AB  - OBJECTIVE: To explore women's views of decision-making relating to hysterectomy.
      DESIGN: Structured questionnaire and in-depth interview surveys. SETTING: A
      teaching hospital and a district general hospital in northeast Scotland. SAMPLE:
      Women scheduled for hysterectomy for benign menstrual problems. METHODS: Pre
      operative questionnaires were sent to a consecutive sample of women booked for
      hysterectomy. A purposive sample was interviewed post-operatively. MAIN OUTCOME
      MEASURES: Women's experiences of, and satisfaction with, information provision,
      communication and decision-making processes; the relationship between views of
      decision-making processes and decisions made. RESULTS: One hundred and four women
      (66%) returned questionnaires. Most responded positively to structured questions
      about the process by which the decision to have a hysterectomy was reached.
      Almost all (97%) reported satisfaction with the decision made. Twenty women were
      interviewed post-operatively. A number, including some who had responded
      positively on the questionnaire, described aspects of the decision-making process
      that were suboptimal. Women's perceptions of the decision-making process,
      including the way their doctors communicated with them, did impinge on their
      views of the course of action selected. Some women had residual doubts about the
      appropriateness of hysterectomy. CONCLUSIONS: In a significant minority of women,
      there are important shortcomings in current patterns of information provision and
      communication relating to decision-making. These are unlikely to be picked up by
      conventional structured patient feedback surveys. Further efforts are required to
      ensure that women are adequately informed and involved in decisions about
      gynaecological treatments.

PMID- 14723751
TI  - Feasibility of central co-ordinated EMA/CO for gestational trophoblastic disease
      in the Netherlands.
AB  - OBJECTIVE: In the Netherlands, high risk gestational trophoblastic disease (GTD)
      patients are treated in different referral hospitals with a national working
      party on trophoblastic tumours having a co-ordinating function. Our purpose was
      to evaluate whether this policy is a satisfactory alternative to complete
      centralisation. DESIGN: A retrospective study of all etoposide, methotrexate,
      actomycin D, cyclophosphamide and vincristine (EMA/CO)-treated women in the
      Netherlands between 1986 and 1997. Data regarding risk factors, treatment results
      and toxicity were collected. SETTING: Ten hospitals; 2 general, 6 academical and
      2 oncology centres. POPULATION: Fifty EMA/CO-treated women registered by the
      central registration unit of the Dutch Working Party on Trophoblastic Disease.
      METHODS: Patients files and quarterly reports of the Dutch Working Party. MAIN
      OUTCOME MEASURES: Cure rate and consistency of treatment in different hospitals.
      RESULTS: EMA/CO treatment was administered in 10 different hospitals. All
      patients were discussed during the meetings of the Dutch Working Party and
      overall, 86% of patients were cured. Consistency in treatment was good.
      CONCLUSIONS: Cure rates were comparable with results of single institution
      series. We conclude that treatment of high risk GTD patients in different
      referral hospitals with concentration of expertise in a working party is a good
      alternative to centralisation of treatment in GTD specialised hospitals.

PMID- 14723752
TI  - Mifepristone and misoprostol versus dilation and evacuation for midtrimester
      abortion: a pilot randomised controlled trial.
AB  - OBJECTIVE: To test the feasibility of mounting a randomised controlled trial
      comparing mifepristone-misoprostol versus dilation and evacuation (D&E) for
      midtrimester abortion. DESIGN: Pilot randomised controlled trial. SETTING:
      University of North Carolina Hospitals, Chapel Hill, North Carolina. POPULATION:
      Women aged 18 years or older and without prior uterine operations who requested
      abortion at 14-19 menstrual weeks of gestation from January 2002 to January 2003.
      METHODS: Participants received either mifepristone 200 mg by mouth followed in
      two days by vaginal then oral misoprostol (Aberdeen regimen) or D&E after one or
      two days of laminaria preparation. Care was provided by residents under faculty
      supervision. MAIN OUTCOME MEASURES: Enrolment rate and acceptability of and
      adverse events associated with methods. RESULTS: The trial was stopped at one
      year because of slow enrolment. Of 47 women eligible for the trial, 29 (62%)
      declined participation, primarily because of a preference for D&E abortion. Among
      the 18 participants enrolled, nine were randomised to treatment with mifepristone
      misoprostol and 9 to D&E. Compared with D&E, mifepristone-misoprostol abortion
      caused more pain and adverse events, although none was serious. CONCLUSIONS: Our
      findings concerning acceptability and adverse events should be considered
      hypothesis-generating; they may prove useful in planning a larger randomised
      controlled trial. Such a trial will be difficult to mount in the US. Hence, we
      suggest that it be done in a setting where labour-induction abortion is the norm.

PMID- 14723753
TI  - The use of oral misoprostol for pre-abortion cervical priming: a randomised
      controlled trial of 400 versus 200 microg in first trimester pregnancies.
AB  - OBJECTIVE: To compare the impact of 200 and 400 microg oral misoprostol on pre
      operative cervical priming in both primi- and multigravidae prior to first
      trimester termination of pregnancy. Pre-operative cervical dilatation and
      bleeding were assessed. DESIGN: Randomised controlled trial. SETTING: Norwegian
      university teaching hospital. SAMPLE: Five hundred and fifty-one women undergoing
      surgical termination of pregnancy between 7 and 12 weeks of gestation. METHODS:
      Patients were randomised to either 200 or 400 microg of oral misoprostol 10-16
      hours before vacuum aspiration. The degree of cervical dilatation prior to
      abortion by vacuum aspiration was measured. Pre-operative bleeding and pain were
      recorded and vaginal bleeding was measured. MAIN OUTCOME MEASURES: Degree of pre
      operative cervical dilatation and pre-operative bleeding. RESULTS: The mean
      cervical dilatation was 5.8 mm (SD 1.7) for the women who received 400 microg
      misoprostol and 5.4 mm (SD 1.4) for those who received 200 microg (P= 0.004). The
      pre-operative dilatation was larger in multigravidae than in primigravidae in
      both dosage groups. The odds ratio (OR) of pre-operative bleeding was 3.3 (95%
      confidence interval [CI] 2.1-5.0) in the 400 microg dosage group, as compared
      with the group receiving 200 microg misoprostol. The occurrence of bleeding was
      dose-dependent. Frequency of bleeding was similar in multigravidae compared with
      primigravidae in the 400 microg dosage group, whereas the occurrence of bleeding
      was less in primigravidae than multigravidae in the 200 microg dosage group. Only
      89 out of 551 patients bled one or more grams. The volumes measured were not
      statistically significantly different. Complications were minor, and were
      distributed equally between the two dosage groups. CONCLUSIONS: The 200 microg
      oral misoprostol compared with the 400 microg oral misoprostol given 10-16 hours
      before first trimester surgical abortions results in less pre-operative vaginal
      bleeding and in a statistically, although not clinically significant reduction in
      cervical dilatation.

PMID- 14723754
TI  - Are reported preterm birth rates reliable? An analysis of interhospital
      differences in the calculation of the weeks of gestation at delivery and preterm
      birth rate.
AB  - We investigated the possibility of preterm birth misclassification as a
      determinant of variation in its reported rates. Using a database of 497,105
      deliveries from 17 hospitals, the best estimate of gestational age made at
      delivery and entered into the database at that time was recalculated from the
      menstrual dates and mid-trimester ultrasound scan. The recalculated completed
      weeks of gestation at delivery was compared with that made at birth. Calculation
      of estimated gestational age varied between hospitals due to inconsistencies in
      'rounding' and 'truncating' the weeks of gestation at delivery. This resulted in
      preterm birth misclassification rates of up to 10.1%.

PMID- 14723755
TI  - Maternal mortality as an indicator of obstetric care in Europe.
AB  - OBJECTIVE: This analysis considers the usefulness of maternal mortality ratio
      (MMR) as an indicator of obstetric care in the context of low overall maternal
      mortality. We explore whether variation in the level of MMR among European
      countries reflects differences in obstetric care. DESIGN: The data presented in
      this article were collected as part of the European Concerted Action on Mothers'
      Mortality and Severe morbidity (MOMS). In this study, a panel of experts followed
      a protocol to determine cause of death and whether it was pregnancy-related. This
      analysis uses the expert panel's confirmation of cause of death and obstetric
      attribution. SETTING: All maternal deaths within 11 European countries.
      POPULATION: Two hundred and ninety obstetric deaths occuring between 1992 and
      1995. METHODS: We present the results of a multivariable analysis that controls
      for cause of death, moment of death, place of death, pregnancy outcome, women's
      age and nationality. MAIN OUTCOME MEASURES: We test the hypothesis that countries
      with higher MMR would have proportionally more cases of direct obstetric death
      due to thromboembolism, hypertension, haemorrhage or infection compared with
      other countries in the study. We examine timing of death and maternal age to
      measure whether there are differences between country groups for older mothers.
      RESULTS: We find distinct patterns in cause and timing of death and age-specific
      mortality ratios between countries with different levels of MMR. CONCLUSIONS:
      Despite low rates of maternal mortality in Europe, between-country differences
      follow patterns with respect to cause and timing of death and maternal age. In
      addition to representing an important indicator of health status in a country,
      differences in MMR among European countries provide insight to where obstetric
      care plays a role maternal deaths.

PMID- 14723756
TI  - Recurrent persistent occipito-posterior position in subsequent deliveries.
AB  - A nine year follow up study of the delivery pattern of 119 women after delivery
      in the persistent occiput posterior position and their occipito-anterior
      controls. The studied parameters were: number of deliveries, number of repeated
      cases of persistent occiput posterior position and operative deliveries.
      Deliveries in the occipito-posterior position were more common in the study group
      than in the controls (P= 0.031). Except for this, no statistically significant
      differences were found between the groups. According to the results, recurrence
      of the persistent occiput posterior position is common. A history of delivery in
      the persistent occiput posterior position does not seem to have any major impact
      on future childbearing.

PMID- 14723757
TI  - Prevalence of bladder neck mobility in asymptomatic non-pregnant nulliparous
      volunteers.
AB  - Antenatal bladder neck mobility is known to be associated with postpartum stress
      incontinence. Whether this represents a normal feature of pregnancy or a
      pathological process is unclear. Forty-eight nulliparous volunteers had perineal
      ultrasound scans to assess bladder neck mobility. Using previously defined
      cutoffs (for incontinence), 50% had increased linear movement and 39% increased
      angle of rotation. This suggests that bladder neck mobility is common in
      asymptomatic nulliparous women. Furthermore, it could represent a risk factor for
      stress incontinence after pregnancy and in the longer term.

PMID- 14723758
TI  - Reduced maternal dexamethasone dosage for the prenatal treatment of congenital
      adrenal hyperplasia.

PMID- 14723759
TI  - A case of generalised oedema secondary to uterine artery embolisation for
      leiomyomata.

PMID- 14723760
TI  - Prelabour rupture of the broad ligament in a primigravida.

PMID- 14723761
TI  - Treatment of severe recurrent endometriosis with an aromatase inhibitor in a
      young ovariectomised woman.

PMID- 14723762
TI  - Adrenal artery rupture in pregnancy.

PMID- 14723763
TI  - An unusual gestational choriocarcinoma occurring primarily on the surface of a
      subserous leiomyoma.

PMID- 14723764
TI  - Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

PMID- 14723765
TI  - Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

PMID- 14723766
TI  - Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

PMID- 14723767
TI  - Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

PMID- 14723769
TI  - Glomerular endotheliosis in normal pregnancy and pre-eclampsia.

PMID- 14723773
TI  - Rural nurse practitioners in South Australia: recognition for registered nurses
      already fulfilling the role.
AB  - The introduction of the nurse practitioner role is hailed as a new initiative in
      the South Australian public health system. In reality, some registered nurses
      working in rural public health care facilities have been practicing in the role
      for many years. The role of the rural registered nurse, the pathway towards
      achieving rural nurse practitioner status and the anticipated advantages of
      implementing the rural nurse practitioner role will be presented.

PMID- 14723774
TI  - Epidemiological study of gambling in the non-metropolitan region of central
      Queensland.
AB  - OBJECTIVE: The purpose of the research was to provide a contemporary description
      of the gambling behaviours of people in Central Queensland. DESIGN: The South
      Oaks Gambling Screen (SOGS), a clinical diagnostic tool for identifying problem
      and pathological gamblers was utilised. SETTING: Central Queensland extends from
      Bundaberg to Mackay and west to the Queensland-Northern Territory border. The
      region incorporates a number of rural and regional centres and the major centres
      of Rockhampton, Gladstone, Mackay and Bundaberg. SUBJECTS: Computer-aided
      telephone interviews were conducted with a random sample of 1029 adults. MAIN
      OUTCOME MEASURES: a comparison of CQ gambling rates with national averages.
      RESULTS: Over 90% of the population had engaged in some form of gambling activity
      in the past month. One point eight percent of the sample fulfilled criteria for
      'problem gambling'. The prevalence of 'probable pathological gambling', was 0.8%.
      An additional 1% of the population were identified as being 'problem gamblers'.
      These rates are slightly lower than the Australian average identified by the
      Productivity Commission in 1999. Nonetheless, they indicate the presence of a
      large number of individuals affected by problem gambling. CONCLUSIONS:
      Comparisons of these data with treatment statistics available from the regional
      counselling service for problem gamblers indicate that the majority of these
      gamblers do not seek treatment. It is clear that many gamblers with serious
      pathology go undetected and untreated. General practitioners are suggested as one
      appropriate point for screening and further referral. A whole-of-government
      approach to problem and pathological gambling is also advocated.

PMID- 14723775
TI  - Implementing computerised workload data collection in rural primary health care.
AB  - OBJECTIVE: Describes the implementation of a computerised information system to
      collect workload data and discusses feedback from staff evaluation of use and
      value. DESIGN: Feedback interviews following service implementation. SETTING:
      Remote rural primary health care, Scotland. SUBJECTS: Thirty-three primary health
      care staff. MAIN OUTCOME MEASURES: Not relevant, as the study was service
      development with qualitative evaluation. RESULTS: Findings of evaluation
      interviews indicate a number of themes common to remote rural practice that make
      implementing a computerised information system problematical. These include:
      logistical problems caused by small practice teams and wide areas covered;
      inadequate allowance for recording of blurred roles and the wide range of non
      clinical duties carried out; lack of local contextual and cultural information,
      which is necessary to make sense of data collected. Remote rural health
      professionals found reports from the system of limited value as they felt they
      already had good knowledge of local activities and had few opportunities, due to
      small teams, to use data for service redesign. CONCLUSION: Remote rural primary
      care is underpinned by a number of organisational and philosophical features that
      require understanding when considering the implementation of initiatives
      developed in an urban working environment.

PMID- 14723776
TI  - Prevalence of overweight and smoking patients with coronary heart disease in
      rural China.
AB  - OBJECTIVE: To investigate the prevalence of overweight and/or smoking patients
      with coronary artery disease in rural China. DESIGN: A prospective survey with
      qualitative, open-ended questionnaires. SETTING: Tertiary referral centre.
      SUBJECTS: 158 hospitalised patients (71 men and 87 women) with established
      coronary heart disease. MAIN OUTCOME MEASURES: To determine the prevalence of
      overweight and/or smoking hospitalised patients who had a definitive diagnosis of
      coronary artery disease and to determine participants understanding of these risk
      factors. RESULTS: Being overweight and smoking cigarettes were found in 32.7% and
      15.2% of the participants, respectively. More than 70% of the overweight
      participants had neither knowledge nor counselling on their weight before the
      study. Most smokers believed smoking was harmful to their health and cardiac
      condition, and had tried unsuccessfully to quit smoking. CONCLUSIONS: There was a
      high prevalence of overweight and/or smoking patients with coronary heart
      disease. A systematic approach is urgently required to educate patients and
      primary care physicians, and to improve the management of being overweight and
      smoking cigarettes.

PMID- 14723777
TI  - Post operative pain experiences of central Australian aboriginal women. What do
      we understand?
AB  - OBJECTIVE: The aim of this study was to explore the postoperative pain
      experiences of Central Australian Aboriginal women and the subsequent
      interpretation of that pain experience by non-Aboriginal female nurses. DESIGN:
      Qualitative study using grounded theory methodology. SETTING: Postoperative
      surgical setting of a Central Australian regional hospital. SUBJECTS: Five
      Aboriginal female clients who had undergone a surgical procedure, eight non
      Aboriginal female nurses and four Aboriginal female health workers employed by a
      Central Australian regional hospital. RESULTS: Aboriginal women have culturally
      appropriate ways of expressing and managing pain that are not well understood by
      non-Aboriginal female nurses. In addition, the Aboriginal women inappropriately
      endow non-Aboriginal nurses with the same powers and skills expected of healers
      from their culture. This phenomenon resulted in the non-Aboriginal nurses lacking
      the cultural insight and the appropriate knowledge and tools required to assess
      and manage the postoperative pain of Central Australian Aboriginal women
      effectively or efficiently. CONCLUSIONS: Non-Aboriginal nurses have a profound
      knowledge deficit about the postoperative pain experiences of Central Australian
      Aboriginal women. This deficit is evident through the use of culturally
      inappropriate and unreliable pain assessment strategies and tools and the
      misinterpretation of traditional pain relief strategies, such as the use of
      pituri, rubbing and centreing. The findings of this study suggested that
      nurse/client interactions related to language and role interpretation were in
      cultural conflict. The nurses expected the Aboriginal women to adopt pain
      behaviours as understood from the nurses' culture. The nurses anticipated that
      the client would contribute to their own care by communicating pain experiences
      in ways that are familiar and are believed to be universal. The Aboriginal women
      expected the nurses to conduct business similar to that of their own traditional
      tribal healers, 'to see within' and to 'just know'.

PMID- 14723778
TI  - Recruitment and retention of rural allied health professionals in developmental
      disability services in New South Wales.

PMID- 14723779
TI  - Doing it together: the Tasmanian interdisciplinary rural placement program.

PMID- 14723780
TI  - Preparing allied health students for fieldwork in smaller communities.

PMID- 14723782
TI  - Has exercise an antifracture efficacy in women?
AB  - Exercise in girls during growth seems to confer a high peak bone mineral density
      (BMD). Exercise in adulthood, in the peri- and postmenopausal period, and in old
      age prevents bone loss or increases BMD with a magnitude of minor biological
      significance. However, these changes must be regarded as beneficial compared to
      the age-related bone loss, which inevitably will occur if no interventions are
      implemented. Prospective intervention studies also suggest that exercise improves
      muscle strength, coordination and balance, even in elderly women, all of which
      are improvements with a potential of reducing the number of falls. A randomised,
      controlled, prospective, blinded study (the only study design that tests a
      hypothesis) of exercise with fracture as end point is extremely difficult to
      conduct, due to the large sample sizes needed. At present, no such studies exist.
      Retrospective and prospective observational and case-control studies suggest that
      physical activity in women is associated with reduced fracture risk. This may be
      correct, but we must never forget that a consistently replicated sampling bias
      may produce the same outcome. The Achilles heel of exercise is the reduction or
      the cessation of physical activity, which commonly occurs among middle-aged women
      when family and work demands reduce the time available for exercise. A higher BMD
      or improvement in muscle size and muscle strength achieved by exercise during
      adolescence seems to be eroded on retirement, leaving virtually no remaining
      benefits in old age, the period when fragility fractures begin to be a problem of
      increasing magnitude. However, recreational activities seem to maintain some of
      the musculo-skeletal benefits, but to date we do not know the level of activity
      needed to retain these benefits. Dose-response relationships need to be
      quantified, as also the effects on bone size, shape and architecture. Another
      essential question that we must address is how many fewer fractures will be the
      result of a community-based exercise campaign. Will efforts by the community to
      encourage a higher level of physical exercise, with the aim of reducing bone
      fractures, be cost-effective? The higher level of proof, suggesting that exercise
      does reduce fragility fractures and thus reduces the total cost for the society,
      must come from well-designed and well-executed, prospective, randomised,
      controlled trials. The responsibility of executing these studies lies in the
      hands of both researchers and the community.

PMID- 14723783
TI  - Regional bone mineral density after resistive training in young and older men and
      women.
AB  - PURPOSE: The purpose of this study was to determine the effects of 6 months of
      whole-body resistive training (RT) on total and regional bone mineral density
      (BMD) and bone mineral content (BMC) by age and gender in young and older men and
      women. METHODS: Younger men (n=10) and women (n=7) aged 20-29 years (25+/-1
      years) and older men (n=10) and women (n=10) aged 65-74 years (69+/-1 years)
      participated in 6 months of progressive whole-body RT. Upper- and lower-body
      strength was assessed by the one repetition maximum (1RM) test, and total body
      fat, lean tissue mass, femoral neck BMD, Ward's triangle BMD, greater trochanter
      BMD, total-body BMD, and L2-L4 spine BMD were determined by dual-energy X-ray
      absorptiometry before and after 6 months of RT. RESULTS: Percent body fat
      decreased only in the young men (P<0.05). Lean tissue mass increased after
      training in young men and women and older men (P<0.05) but did not change
      significantly in older women. Upper- and lower-body 1RM strength increased in all
      groups (P<0.01). Overall, there was a significant increase in BMD at the femoral
      neck, ward's triangle and greater trochanter BMD, as well as total body BMC and
      leg BMC (P<0.05). Total-body BMD and L2-L4 spine BMD did not change with RT.
      There were no gender differences in the training response between men and women
      for any of the BMD regions and no age differences in the training response,
      except for a trend between young and older subjects for femoral neck (P<0.08).
      CONCLUSION: A 6-month RT program increases muscle mass and improves BMD of the
      femoral region in young and healthy older men and women as a group, with a trend
      for this to be greater in young subjects.

PMID- 14723784
TI  - Muscle strength correlates with total body bone mineral density in young women
      but not in men.
AB  - BACKGROUND: Osteoporosis is a growing health problem. One of the proposed reasons
      for this is a more sedentary lifestyle. The aim of this study was to investigate
      the associations between muscle strength and total body bone mineral density
      (TBMD) in young adults at expected peak bone mass. METHODS: Sixty-four women and
      61 men (total 125) 21 years of age were included. Handgrip strength, isokinetic
      knee-flexion and -extension muscle strength, TBMD, and body composition were
      measured. RESULTS: Univariate regression analyses showed that knee flexion and
      extension explained almost 30% of the variation in TBMD in women, whereas
      handgrip strength was not associated with TBMD. In men, no correlation between
      any measures of muscle strength and TBMD was evident. Stepwise regression
      analysis showed that knee-flexion and -extension muscle strength in women were
      associated with TBMD, R2=0.27. In men, lean body mass, fat mass, weight, and
      height were predictors for TBMD, R2=0.43, whereas muscle strength did not affect
      the prediction of TBMD. CONCLUSIONS: Muscle strength at weight-bearing sites is
      related to TBMD in women, whereas body composition is related to TBMD in men. The
      association of lower limb strength on TBMD only in young women indicates a gender
      difference.

PMID- 14723785
TI  - Contralateral tendon rupture risk is increased in individuals with a previous
      Achilles tendon rupture.
AB  - The purpose of this study was to examine the outcome after surgery for an acute
      Achilles tendon rupture. In particular, we wanted to study whether persons who
      have suffered an Achilles tendon rupture are at greater risk of a contralateral
      tendon rupture. From September 1990 to April 1997, 168 acute Achilles tendon
      ruptures in 26 women and 142 men were treated operatively. In August 1998
      (median: 4.2 years post injury), 154 of these patients (92%) responded to a
      follow-up questionnaire. Local symptoms (pain, decreased strength and/or reduced
      range of motion) were reported pre injury by 25% of the patients; at follow-up
      this had increased to 52%. Ten patients (6%) experienced a rupture on the
      contralateral side during the follow-up period (OR: 176 [70-282] vs. the expected
      rate based on the general population risk of this injury, P<0.001). Thus, this
      study suggests that patients with an Achilles tendon rupture are at significantly
      increased risk of a contralateral tendon rupture, as well. Also, as many as half
      of the patients suffered from post-injury problems at long-term follow-up.

PMID- 14723786
TI  - Risk for injury when playing in a national football team.
AB  - The Swedish male senior national football team was followed prospectively between
      1991 and 1997. During these 6 years, the team played 73 official matches and had
      three training camps. The senior author (J. E.) attended 57 of these matches and
      the three training camps and these matches and training camps, are included in
      the present study. Exposure to football was recorded individually for each
      player. The team physician examined all injuries. Total exposure was 7245 h (6235
      training and 1010 match hours) and there were 71 injuries (40 training and 31
      match injuries). Five (16%) of the match injuries were major, with more than 4
      weeks of absence from football. The injury incidence during training was 6.5/1000
      h and the injury risk during matchplay was 30.3/1000 h. A significantly higher
      injury incidence was found for matches lost compared to matches won or drawn
      (52.5 vs. 22.7/1000 h, P=0.026). No statistically significant difference for
      injury was found between competitive matches and friendly matches. No difference
      was found between home and away matches or matches on neutral ground. The risk
      for injury when playing in a national team compares with previously reported
      figures for professional football at a high level.

PMID- 14723787
TI  - Immuno-endocrine and metabolic responses to long distance ski racing in world
      class male and female cross-country skiers.
AB  - The purpose of this study was to characterize the extent of immune, endocrine,
      substrate and metabolic changes during a long-distance cross-country ski race in
      extremely well-trained athletes and evaluate if the blood perturbations would
      indicate signs of health risk. Ten male (M) and six female (F) national team
      skiers were investigated as they followed their usual routines of race
      preparations. Blood samples were drawn before and immediately after a World Cup
      50-km M and 30-km F ski race with a mean finish time of 142 and 104 min,
      respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged
      for both M and F. Serum testosterone remained unchanged in M, but doubled in F.
      Significant increases were observed in concentrations of granulocytes (F: 5 x, M:
      5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x),
      noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5
      x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid
      (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin
      concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration
      increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in
      several immuno-endocrine, substrate and metabolic measurements after long
      distance cross-country ski racing and suggest that some of these marked changes
      may reflect the large amount of muscle mass involved during skiing.

PMID- 14723788
TI  - Gait asymmetry in patients with limb length discrepancy.
AB  - Foot loading patterns and neuromuscular function of both limbs during walking
      were investigated on 25 patients with limb length discrepancy. Plantar pressures
      and 2-D ground reaction forces were recorded simultaneously with
      electromyographic activities at two different walking speeds. Bilateral
      comparison indicated that moderate limb length discrepancies resulted in
      asymmetrical gait patterns. The duration of the stance phase was reduced in the
      short limb in both walking speeds. The vertical ground reaction force (F) in the
      push-off phase was greater in the long limb both at normal (1.33 (SO, 0.05 BW)
      vs. 1.29 (SD, 0.09 BW)) (P=0.0027) and fast walking speed (1.55 (SD, 0.11) vs.
      1.48 (SD, 0.15 BW)) (P=0.001). Peak plantar pressures were higher under the big
      toe in the long leg and the heel-off occurred faster. The push-off phase was
      initiated earlier in the short leg. The maximum isometric torque of the long limb
      was considerably greater (673 Nm vs. 239 Nm) (P=0.026). The results imply that
      the loading of the long limb is greater and the foot loading patterns shifted
      more to the forefoot in the long, limb to compensate walking disturbances caused
      by limb length discrepancies.

PMID- 14723789
TI  - Perceived parental beliefs about the causes of success in sport: relationship to
      athletes' achievement goals and personal beliefs.
AB  - This study examined the relationship between perceived parental beliefs and young
      athletes' achievement goal orientations and personal beliefs about the causes of
      success in sport. Participants were 183 male and female athletes, 11-18 years
      old, involved in team sports. Athletes completed the Task and Ego Orientation in
      Sport Questionnaire, the Beliefs about the Causes of Sport Success Questionnaire,
      and two modified versions of the latter inventory to assess their perceptions of
      their parents' beliefs. Canonical correlation analysis revealed that perceived
      parental beliefs were related to goal orientations and personal beliefs in a
      conceptually coherent fashion. Thus, the perceived parental belief that effort
      leads to success in sport was related to athletes' task orientation and personal
      belief that effort causes sport success. In contrast, the perceived parental
      beliefs that superior ability, external factors, and using deceptive tactics are
      precursors to success in sport corresponded to athletes' ego orientation and the
      same personal beliefs. The findings are discussed in terms of their implications
      for understanding the socialization experiences of young athletes.

PMID- 14723791
TI  - Caregiving process and caregiver burden: conceptual models to guide research and
      practice.
AB  - BACKGROUND: Parental care for a child with a developmental disability is an
      enormous responsibility, one that can far exceed that of typical parental care.
      While most parents adapt well to the situation of caring for a child with a
      disability, some do not. To understand parents' adaptations to their children's
      disabilities, the complex nature of stress processes must be accounted for and
      the constructs and factors that play a role in the caregiving must be considered.
      DISCUSSION: Evidence suggests that there is considerable variation in how
      caregivers adapt to their caregiving demands. Many studies have sought to qualify
      the association between caregiving and health outcomes of the caregivers.
      Contextual factors such as SES, child factors such as child behaviour problems
      and severity of disability, intra-psychic factors such as mastery and self
      esteem, coping strategies and social supports have all been associated with
      psychological and/or physical outcome or parents or primary caregivers. In
      reviewing these issues, the literature appears to be limited by the use of
      traditional analytic approaches which examine the relationship between a factor
      and an outcome. It is clear, however, that changes to single factors, as
      represented in these studies, occur very rarely even in the experimental context.
      The literature has also been limited by lack of reliance on specific theoretical
      frameworks. SUMMARY: This conceptual paper documents the state of current
      knowledge and explores the current theoretical frameworks that have been used to
      describe the caregiving process from two diverse fields, pediatrics and
      geriatrics. Integration of these models into one comprehensive model suitable for
      this population of children with disabilities and their caregivers is proposed.
      This model may guide future research in this area.

PMID- 14723792
TI  - Cluster randomized trial of an active, multifaceted information dissemination
      intervention based on The WHO Reproductive health library to change obstetric
      practices: methods and design issues [ISRCTN14055385].
AB  - BACKGROUND: Effective strategies for implementing best practices in low and
      middle income countries are needed. RHL is an annually updated electronic
      publication containing Cochrane systematic reviews, commentaries and practical
      recommendations on how to implement evidence-based practices. We are conducting a
      trial to evaluate the improvement in obstetric practices using an active
      dissemination strategy to promote uptake of recommendations in The WHO
      Reproductive Health Library (RHL). METHODS: A cluster randomized trial to improve
      obstetric practices in 40 hospitals in Mexico and Thailand is conducted. The
      trial uses a stratified random allocation based on country, size and type of
      hospitals. The core intervention consists of three interactive workshops
      delivered over a period of six months. The main outcome measures are changes in
      clinical practices that are recommended in RHL measured approximately a year
      after the first workshop. RESULTS: The design and implementation of a complex
      intervention using a cluster randomized trial design are presented. CONCLUSION:
      Designing the intervention, choosing outcome variables and implementing the
      protocol in two diverse settings has been a time-consuming and challenging
      process. We hope that sharing this experience will help others planning similar
      projects and improve our ability to implement change.

PMID- 14723793
TI  - Molecular cloning and characterization of the mouse Acdp gene family.
AB  - BACKGROUND: We have recently cloned and characterized a novel gene family named
      ancient conserved domain protein (ACDP) in humans. To facilitate the functional
      study of this novel gene family, we have cloned and characterized Acdp, the mouse
      homologue of the human ACDP gene family. RESULTS: The four Acdp genes (Acdp1,
      Acdp2, Acdp3 and Acdp4) contain 3,631 bp, 3,244 bp, 2,684 bp and 2,743 bp of cDNA
      sequences, and encode deduced proteins of 951, 874, 713 and 771 amino acids,
      respectively. The mouse Acdp genes showed very strong homologies (>90%) in both
      nucleotide and amino acid sequences to their human counterparts. In addition,
      both nucleotide and amino acid sequences within the Ancient Conserved Domain
      (ACD) are highly conserved in many different taxonomic species. Particularly,
      Acdp proteins showed very strong AA homologies to the bacteria CorC protein (35%
      AA identity with 55% homology), which is involved in magnesium and cobalt efflux.
      The Acdp genes are widely expressed in all tissues tested except for Acdp1, which
      is only highly expressed in the brain with low levels of expression in kidney and
      testis. Immunostaining of Acdp1 in hippocampus neurons revealed a predominant
      localization on the plasma membrane. CONCLUSION: The Acdp genes are
      evolutionarily conserved in diverse species and ubiquitously expressed throughout
      development and adult tissues suggesting that Acdp may be an essential gene. Acdp
      showed strong homology to bacteria CorC protein and predominantly localized on
      the plasma membrane. These results suggest that Acdp is probably a family of
      proteins involved in ion transport in mammalian cells

PMID- 14723794
TI  - Methods for high throughput validation of amplified fragment pools of BAC DNA for
      constructing high resolution CGH arrays.
AB  - BACKGROUND: The recent development of array based comparative genomic
      hybridization (CGH) technology provides improved resolution for detection of
      genomic DNA copy number alterations. In array CGH, generating spotting solution
      is a multi-step process where bacterial artificial chromosome (BAC) clones are
      converted to replenishable PCR amplified fragments pools (AFP) for use as
      spotting solution in a microarray format on glass substrate. With completion of
      the human and mouse genome sequencing, large BAC clone sets providing complete
      genome coverage are available for construction of whole genome BAC arrays.
      Currently, Southern hybridization, fluorescent in-situ hybridization (FISH), and
      BAC end sequencing methods are commonly used to identify the initial BAC clone
      but not the end product used for spotting arrays. The AFP sequencing technique
      described in this study is a novel method designed to verify the identity of
      array spotting solution in a high throughput manner. RESULTS: We show here that
      Southern hybridization, FISH, and AFP sequencing can be used to verify the
      identity of final spotting solutions using less than 10% of the AFP product.
      Single pass AFP sequencing identified over half of the 960 AFPs analyzed.
      Moreover, using two vector primers approximately 90% of the AFP spotting
      solutions can be identified. CONCLUSIONS: In this feasibility study we
      demonstrate that current methods for identifying initial BAC clones can be
      adapted to verify the identity of AFP spotting solutions used in printing arrays.
      Of these methods, AFP sequencing proves to be the most efficient for large scale
      identification of spotting solution in a high throughput manner.

PMID- 14723796
TI  - Retraction: TGFbeta1 signaling via alphaVbeta6 integrin.

PMID- 14723795
TI  - The antithrombotic profile of aspirin. Aspirin resistance, or simply failure?

PMID- 14723797
TI  - Retraction: TGFbeta1 activates c-Jun and Erk1 via alphaVbeta6 integrin.

PMID- 14723798
TI  - Electrophysiological evaluation of phrenic nerve injury during cardiac surgery--a
      prospective, controlled, clinical study.
AB  - BACKGROUND: According to some reports, left hemidiaphragmatic paralysis due to
      phrenic nerve injury may occur following cardiac surgery. The purpose of this
      study was to document the effects on phrenic nerve injury of whole body
      hypothermia, use of ice-slush around the heart and mammary artery harvesting.
      METHODS: Electrophysiology of phrenic nerves was studied bilaterally in 78
      subjects before and three weeks after cardiac or peripheral vascular surgery. In
      49 patients, coronary artery bypass grafting (CABG) and heart valve replacement
      with moderate hypothermic (mean 28 degrees C) cardiopulmonary bypass (CPB) were
      performed. In the other 29, CABG with beating heart was performed, or, in several
      cases, peripheral vascular surgery with normothermia. RESULTS: In all patients,
      measurements of bilateral phrenic nerve function were within normal limits before
      surgery. Three weeks after surgery, left phrenic nerve function was absent in
      five patients in the CPB and hypothermia group (3 in CABG and 2 in valve
      replacement). No phrenic nerve dysfunction was observed after surgery in the CABG
      with beating heart (no CPB) or the peripheral vascular groups. Except in the five
      patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency
      time (ms) and amplitude (mV) did not differ statistically before and after
      surgery in either group (p > 0.05). CONCLUSIONS: Our results indicate that CPB
      with hypothermia and local ice-slush application around the heart play a role in
      phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury
      during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus
      valve surgery).

PMID- 14723803
TI  - [More efforts should be made to improve the level of diagnosis and treatment of
      infectious diseases of newborn infants].

PMID- 14723804
TI  - [Clinical and immunological studies on neonatal infectious pneumonia].
AB  - OBJECTIVE: To explore etiology, clinical manifestation and immunological changes
      of infectious pneumonia of neonates in Chengdu area. METHODS: Serum specimens
      were collected from 111 infants with infectious pneumonia. Eight viral and
      mycoplasmal specific serum IgM antibodies were detected by enzyme linked
      immunosorbent assay (ELISA); C reactive protein (CRP), total IgG and its
      subclasses, IgA and IgM were determined by rate scattered nephelometry; T
      lymphocyte subpopulations were detected by biotin-streptavidin-peroxidase method,
      and clinical and other laboratory data were analyzed. RESULTS: (1) Etiological
      agents: specific serum IgM antibodies were positive in 40 of 111 cases (36.0%)
      with pneumonias. All the 30 control infants were negative for the specific serum
      IgM antibodies. Among 111 infants with infectious pneumonia, 20.7% had single
      viral or mycoplasmal infection, 40.5% had bacterial infection, 15.3% had viral
      and mycoplasmal infection with bacterial infection; 23.4% had infection with
      unknown agents. (2) The most common clinical manifestations were tachypnea and
      cyanosis. The next were cough, milk choking, rales, retractions of the
      supraclavicular, intercostal and subcostal areas. Roentgenographic examination
      commonly revealed vague opacities, increased density and patchy infiltration. (3)
      Immune status: (1) CD(3), CD(4) cell counts of infants with pneumonias were lower
      than those of the controls while their serum IgA, IgM concentrations were higher
      than those of the control. (2) The CD(3) and CD(4) cell counts of the group with
      bacterial infection were lower than those of the control group. (3) The serum IgA
      concentration of the group with viral and mycoplasmal infection was higher than
      those of the control group and the group with unknown infection. (4) The serum
      IgM concentration of the group with bacterial infection was higher than those of
      the control group. (5) There were no significant differences in CD(8) cell
      counts, CD(4)/CD(8), concentration of serum IgG and IgG(1 - 4) between pneumonia
      group and the control group, and among various infectious groups and the control.
      CONCLUSION: Pathogens of neonatal infectious pneumonia in Chengdu area included
      single viral or mycoplasmic infection or bacterial infection, viral and
      mycoplasmal infection with bacterial infection, and unknown infection.
      Immunological changes of newborn infants suffered from infectious pneumonia
      included declined CD(3) and CD(4) cell counts, particularly in bacterial
      infection.

PMID- 14723805
TI  - [Atrial flutter in a neonate].

PMID- 14723806
TI  - [Early diagnosis of the premature infant nosocomial infection by clinical
      assessment].
AB  - OBJECTIVE: To study the possibility of bacterial infections in the hospital among
      the premature and low birth weight newborns by scoring their clinical assessments
      and laboratory examinations. METHODS: From January 2002 to January 2003, 62
      newborns with birth-weight less than 2,000 g were divided into two groups,
      infected group and control group, based on the current diagnostic standards for
      newborns. We scored the newborns according to the severity of their illnesses
      based on their clinical manifestations and laboratory examination, and compared
      the scores obtained before and after effective antibiotic treatment. RESULTS: It
      was found that the scores were significantly different (P < 0.01) between the
      infected group and the control group before treatment; while after antibiotic
      treatment, the difference was no longer significant (P > 0.05). In the infected
      group, the scores obtained pre- and post-treatment were significantly different
      (P < 0.01). In the control group, in those with the scores >or= 11 before
      antibiotic treatment, the scores significantly decreased (P < 0.01) after
      treatment; but in those with the scores < 11, the score did not decrease (P >
      0.05). These results indicate that the current diagnostic criteria for newborns
      may not be sensitive enough for premature infants, low birth weight infants and
      very low birth weight infants. CONCLUSION: Scoring the low birth weight premature
      infants with their clinical manifestations has the advantages in judging the
      possibility of infection and monitoring the effectiveness of the anti-infection
      treatment.

PMID- 14723807
TI  - [Experimental study on cerebral white matter damage in neonatal rat after
      intrauterine Escherichia coli infection].
AB  - OBJECTIVE: To investigate the expression of glial fibrillary acidic protein
      (GFAP), GFAP mRNA and interleukin-1beta mRNA (IL-1beta mRNA), tumor necrosis
      factor-alpha mRNA (TNF-alpha mRNA) in neonatal rat brain after intrauterine
      infection. METHODS: Escherichia coli (E. coli) was inoculated into both uterine
      horns of pregnant rats when gestation was 70% complete (15 days). The control
      group was treated with normal saline. The pups were killed on the postnatal day 1
      (P1), P3 and P7, respectively. The cerebral white matter damage of the neonatal
      rats was determined by HE staining. Immunohistochemistry was used for evaluation
      of GFAP expression in neonatal rat brains and RT-PCR to analyze GFAP mRNA, IL
      1beta mRNA and TNF-alpha mRNA expression at P1, P3 and P7. RESULTS: The major
      histopathological changes in neonatal cerebral white matter at P7 after
      intrauterine infections were: weak staining of cerebral white matter and focal
      rarefaction. GFAP-positive cells were observed in both the control and the E.
      coli-treated groups. The numbers of GFAP-positive cells of the E. coli-treated
      group pups were markedly increased in periventricular white matter and
      hippocampus at P7 compared with those of the control group (periventricular white
      matter: 9.73 +/- 3.55 vs 5.67 +/- 1.90, P < 0.05 and hippocampus: 7.81 +/- 3.61
      vs 2.16 +/- 1.11, P < 0.05, respectively). No significantly different levels of
      GFAP expression in corpus callosum were found between two groups (P > 0.05). The
      expression of GFAP mRNA in brain of the E. coli-treated neonatal rat was higher
      than the control at P1, P3 (P1: 0.25 +/- 0.07 vs 0.15 +/- 0.08, P < 0.05 and P3:
      0.50 +/- 0.09 vs 0.39 +/- 0.08, P < 0.05, respectively), but the expression of
      GFAP mRNA in brain of the neonatal rat at P7 had no significant difference
      between two groups (P > 0.05). The expression of IL-1beta mRNA and TNF-alpha mRNA
      in brain of the E. coli-treated neonatal rat were higher than of the control at
      P1 (IL-1beta mRNA: 0.83 +/- 0.19 vs 0.50 +/- 0.30, P < 0.05 and TNF-alpha mRNA:
      0.74 +/- 0.30 vs 0.30 +/- 0.20, P < 0.05, respectively), but the expression of IL
      1beta mRNA and TNF-alpha mRNA in brain of the neonatal rat at P3 and P7 had no
      significant difference between two groups (P > 0.05). CONCLUSIONS: The
      intrauterine infection could cause neonatal white matter damage and IL-1beta, TNF
      alpha may be a mechanism mediating between the two events.

PMID- 14723808
TI  - [Protocol for diagnosis and treatment of neonatal septicemia].

PMID- 14723809
TI  - [Problems in and strategies for antibiotics treatment of neonatal infections].

PMID- 14723810
TI  - [Progresses in diagnosis and treatment of intrauterine infection with
      cytomegalovirus and human parvovirus B19].

PMID- 14723811
TI  - [Progress in the clinical use of anti-arrhythmic drugs].

PMID- 14723812
TI  - [Summary of the 2003 National Symposium of Neonatal Infection and Critical
      Illnesses].

PMID- 14723813
TI  - [Neuroprotective effect and mechanisms of hypothermia in neonatal rat cerebral
      hypoxic-ischemic damages].
AB  - OBJECTIVE: Recent studies suggest that hypothermia may be a potential treatment
      for perinatal hypoxic-ischemic (HI) brain damage. But the mechanisms of this
      effect are not well known. In the present study, the protective effect of
      systemic hypothermia as well as effect on apoptosis and associated biochemical
      events were investigated on neonatal rats with HI brain damage. METHODS: Seven
      day-old Wistar rats were subjected to left carotid artery ligation and hypoxia
      was persisted for 60 min. Immediately at the end of hypoxia, the animals were
      maintained either at 36 degrees C or 30 degrees C for 10 h at random. Caspase-2,
      3 activity in brain homogenate was detected with Western blotting at 24 h post-HI
      (n = 8 for each group). Immunoactivity of microtubule-associated protein-2 (MAP
      2), active caspase-3, apoptosis inducing factor (AIF) and oligonucleotide hairpin
      probe staining were detected at 72 h post-HI. The infarct volume, neuronal loss
      in CA(1) sector of hippocampus as well as brain injury scoring were calculated
      according to MAP-2 staining and hematoxylin and eosin staining. RESULTS: Caspase
      2, 3 activities were much higher in the normothermia group [(27.7 +/- 14.7),
      (94.9 +/- 53.1) pmol/(min.mg protein)] at 24 h post-HI than those of hypothermia
      [(7.9 +/- 3.4), (21.1 +/- 18.7) pmol/(min.mg protein)] and normal control groups
      [(7.6 +/- 0.7), (12.9 +/- 0.5) pmol/(min x mg protein)] (P < 0.01). The
      activities were not significantly different between hypothermia group and normal
      control group. Western blotting showed that caspase-3 activation process was
      blocked by hypothermia. The number of active caspase-3 and AIF positive cells in
      the cortex of ipsilateral hemisphere was much higher in the normothermia group
      (median: 148.5; 22/field) than that of hypothermia group (median: 48.5; 9/field)
      (P < 0.05). The number of apoptotic cells as judged by oligonucleotide hairpin
      probe labeling was much higher in normothermia group (median: 144/field) than
      that of hypothermia group (median: 133/field) (P < 0.05). The brain injury
      scoring, infarct volume and neuronal loss in CA(1) area of hippocampus were much
      less in the hypothermia group [10.4 +/- 2.9; 40.5 +/- 34.8)mm(3); 25.7 +/- 11.5]
      than that of normothermia group [14.2 +/- 3.5; (73.9 +/- 22.4) mm(3); 37.4 +/-
      10.6, P < 0.05]. CONCLUSIONS: Systemic hypothermia for 10 h after hypoxia
      ischemia seemed to be effective in reducing brain damage and the mechanism is
      associated with alteration of apoptotic pathway.

PMID- 14723814
TI  - [Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency
      (glutaric aciduria type II)].
AB  - OBJECTIVE: Glutaric aciduria type II, or multiple acyl-CoA dehydrogenase
      deficiency is an autosomal recessively inherited defect of mitochondrial energy
      metabolism. The authors report two cases of late-onset glutaric aciduria type II,
      and evaluate the procedures for the diagnosis and treatment of this rare disease.
      METHODS: The clinical and biochemical characteristics of 2 patients with late
      onset glutaric aciduria type II were documented. Case 1 presented with lipid
      storage myopathy for 3 years. Case 2 presented with intermittent episodes of non
      ketotic hypoglycemia and muscle weakness for 9 years. The diagnosis of the 2
      cases was confirmed with gas chromatography/mass spectrometry analysis of urine
      samples. Riboflavin supplementation and a low-fat, low-protein, high-carbohydrate
      diet were initiated as soon as the diagnosis was made. RESULTS: Organic acid
      analysis on both untreated cases revealed massive glutaric acid with elevated
      concentrations of isovalerylglycine, isobutyrylglycine, ethylmalonic acid, adipic
      acid, suberic acid and other dicarboxylic acids. The clinical manifestations were
      improved remarkably after the administration of riboflavin and diet control.
      Consistent improvements of sera enzymes and urine organic acids were observed
      during the course of treatment. CONCLUSION: Patients with unexplained myopathy,
      metabolic acidosis or hypoglycemia should be carefully screened for inherited
      metabolic disorders. Riboflavin in conjunction with appropriate diet control is
      an effective therapeutic regime for patients with late-onset glutaric aciduria
      type II.

PMID- 14723815
TI  - [Successful rescue of a child with critical autoimmune hemolytic anemia in whom
      transfusion was difficult].

PMID- 14723816
TI  - [Regulation of NF-kappaB/P65 by MDM2 in acute lymphoblastic leukemia in
      childhood].
AB  - OBJECTIVE: MDM2 is considered a proto-oncogene due to its ability to inhibit P53
      tumor-suppressor function. But, evidence showed that MDM2 might have a P53
      independent role in tumorigenesis. MDM2 is over-expressed in human sarcoma and
      carcinoma. Recent studies showed that MDM2 might act as a transcriptional factor
      to modulate expressions of other genes involved in cell cycle regulation and
      transformation. In the present study, the investigators hypothesized that MDM2
      directly affected NF-kappaB expression and function in a P53-independent manner.
      METHODS: MDM2 was transfected to acute lymphoblastic leukemia (ALL) line EU-4
      cells lacking P53 expression and expressing very low levels of MDM2. MDM2 and P65
      expression in mRNA level and protein level were detected by Western blot and
      Northern blot after transfection. Since the expression of E-selectin is P65
      dependent, E-selectin promoter-CAT construct and P65 and MDM2 expression plasmids
      were co-transfected to EU-4 cells. CAT activation was determined with ELISA. The
      effect of adriamycin (ADM) at the concentrations of 15 micro g/ml, 7.5 micro
      g/ml, 5 micro g/ml and 1 micro g/ml on MDM2-transfected EU-4 cells and the parent
      cells was detected by MTT assay. RESULTS: The results showed that MDM2 up
      regulated P65 expression at both mRNA and protein levels, and MDM2 increased P65
      mediated transactivation of E-selectin promoter. Without P65, MDM2 had no effect
      on the transactivation of E-selectin. Moreover, MDM2 antisense could not change
      the transactivation of E-selectin. MTT results showed that the survival rate of
      MDM2 transfected EU-4 cells was higher than that of parental cells. The results
      suggested that MDM2 transfection increase drug resistance of EU-4 cells to ADM
      compared with parent cells. CONCLUSION: (1) MDM2 up-regulated transcriptionally
      P65 expression. (2) MDM2 increased drug resistance of leukemia cells to ADM. (3)
      MDM2 elevated NF-kappaB activity in a P53-independent manner in childhood
      lymphoblastic leukemia cell line.

PMID- 14723817
TI  - [Major histocompatibility complex class II transactivator (CIITA) hammer- head
      ribozyme transfer inhibits major histocompatibility complex class II (MHC-II)
      expression in Jukart cells].
AB  - OBJECTIVE: Graft versus host disease (GVHD), a major cause of graft failure in
      allo-hematopoietic cell transplantation, was associated with the presence of
      major histocompatibility complex class II (MHCII), also called human leukocyte
      antigen (HLAII), on the tissues and organs of host. MHCII played a critical role
      in the induction of immune responses by presenting fragments of allo-antigenic
      peptides to CD(4)(+) T lymphocytes, then by resulting in CD(8)(+) T lymphocytes
      activation. Therefore, it was very important for compatibility of MHCII in allo
      transplantation. But it was impossible to down-modulate MHCIIexpression directly.
      There were codominance and multiple allele for MHCII molecules which was owing to
      their complicated polymorphism, therefore it was difficult to repress every MHCII
      molecule expression. MHC class II transactivator (CIITA) was the major rate
      limiting factor for both constitutive and inducible MHCIIexpression., and with
      rare exceptions, its expression paralleled that of MHCII transcripts. This study
      investigated the effect of anti-CIITA hammerhead ribozyme (Rz) on interferon
      (IFN)-gamma induced MHCII expression in Jukart cell line. METHODS: Three
      hammerhead Rz specific to 134, 218, 464 sites of CIITA gene were synthesized and
      named as Rz134, Rz218, Rz464, respectively. Then they were cloned into the
      EcoRI/BamHI of vector pGEM-7zf(+). CIITA target gene was obtained from Raji cell
      by RT-PCR, and then inserted also into the pGEM-7zf(+) plasmid. The above
      recombinant plasmids were screened out by sequence analysis. Hammerhead Rz and
      their target RNA were transcribed and then mixed up and incubated in vitro. The
      cleavage products were analyzed by PAGE and silver-staining. Rz464 was selected
      as the one with the highest activity, and then inserted into the plasmid with
      internal ribosome entry site-enhanced green fluorescent protein (pIRES2-EGFP),
      pRz464. Stable transfectants of Jukart cell line with pRz464 (pRz464-J) were
      tested for classic MHCII (HLA-DR, DP, DQ) induction by recombinant human IFN
      gamma. mRNA abundance of CIITA was measured by RT-PCR. RESULTS: When induced with
      IFN-gamma, the expression of HLA-DR, DP, DQ in pRz464 positive (pRz464+) Jukart
      cells was 2.7%, 6.4% and 2.1%, respectively, and that in Jukart cells transfected
      by non-related ribozyme was 10.1%, 57.8% and 5.1%, respectively. Therefore, Rz464
      suppressed IFN-gamma-induced up-regulation of HLA-DR, DP and DQ by 73.27%, 88.93%
      and 58.82%, respectively. Meanwhile, the mRNA content of CIITA was reduced
      significantly (P < 0.01). CONCLUSION: CIITA hammerhead ribozyme transfer
      inhibited MHC-II expression in Jukart cells. The above result provided insight
      into the future application of anti-CIITA hammerhead ribozyme for the antigen
      specific tolerance induction and anti-GVHD treatment in the hematopoietic stem
      cell transplantation.

PMID- 14723818
TI  - [Relationship between single nucleotide polymorphisms in thiopurine
      methyltransferase gene and tolerance to thiopurines in acute leukemia].
AB  - OBJECTIVE: For the purpose of clarifying the influence of thiopurine
      methyltransferase (TPMT) gene single nucleotide polymorphisms (SNPs) on the
      efficacy of thiopurines and risk for its toxicity and therefore improving the
      safety and efficacy of thiopurines, the authors investigated TPMT genotype in
      acute leukemia in children who were intolerant to the treatment with 6-mercap
      topurine (6-MP). METHODS: TPMT genotype was determined in an unrelated population
      of 250 Chinese healthy blood donors and 280 children with acute leukemia. TPMT
      genotyping assay was based on polymerase chain reaction (PCR), restriction
      digestion of PCR products, denaturing high-performance liquid chromatography
      (DHPLC) and direct DNA sequencing in the TPMT * 2 (G238C), TPMT * 3A (G460A,
      A719G) and TPMT * 3C (A719G). RESULTS: There were 10 TPMT * 1/TPMT * 3C
      heterozygotes in 280 children. The frequency of the polymorphism was 3.6%. All
      the involved alleles were TPMT * 3C. Of the 160 children acute leukemia
      evaluated, 45 (26%) were intolerant to 6-MP. Presentations included
      hepatotoxicity and hematological toxicity. Six out of 45 children were
      heterozygous, while the other 39 were wild type homozygous. Before dosage
      adjustments for thiopurine, the hematologic toxicity and hepatotoxicity in TPMT
      heterozygous individuals occurred more frequently than in homozygous. Therefore,
      cases of TPMT heterozygotes experienced more missed doses of 6-MP. CONCLUSIONS:
      TPMT genotype is associated with tolerance in acute leukemia in children. The
      heterozygote individuals have low TPMT activity. Therefore the frequencies of
      hemtopoietic toxicity and hepatoxicity are high after using 6-MP. Detection of
      SNPs in the TPMT genes is useful in identifying children before administration of
      6-MP.

PMID- 14723819
TI  - [Chymothorax in a newborn infant].

PMID- 14723820
TI  - [Damage to peripheral nerves induced by Campylobacter jejuni exotoxin].
AB  - OBJECTIVE: To explore the pathogenesis of the damage to peripheral nerves induced
      by Campylobacter jejuni exotoxin (CJT). METHODS: (1) Animal models: (1) The CJT
      was extracted from PEN 19-CJ and injected perineurally and intravenously to
      Wistar rats. (2) The sera and the supernatants of peripheral blood mononuclear
      cells (PBMCs), taken from the rats immunized with the CJT, were injected
      perineurally at sciatic nerves of experimental rats and intravenously,
      respectively. (2) Histopathologic study of sciatic nerves: the animals were
      sacrificed and their sciatic nerves were examined for tease fibers, transverse
      section with toluidine blues staining and electron microscopy. (3)
      Immunohistochemistry: sections of sciatic nerves of either normal rats or human
      which were incubated with CJT and the sciatic nerves with pathological changes
      induced by CJT were obtained for observation of the binding capability of CJT
      with peripheral nerves by SABC and FITC-immunofluorescence methods, and nucleic
      acid hybridization techniques for detection of TNF-alpha mRNA expression in
      pathological sciatic nerves samples. RESULTS: (1) Remarkable peripheral
      neuropathies with axon degeneration and/or demyelination were found in the nerves
      induced by both CJT injection perineurally and intravenously. The axon
      degeneration was more obvious. Pathological changes were identified in 76.8%
      (2,763/3,600) of teasing fibers after perineural injection, but only 9.6%
      (230/2,400) of fibers were damaged in control group (P < 0.01). The peak severity
      of fiber damage was found on the 3rd day after CJT intravenous injection with the
      incidence of abnormal fibers was 19.5% (390/2,000), and abnormalities of 15.5%
      (310/2000) on the 14th day. However, no abnormal changes were demonstrated in
      control group (P < 0.01). So was in the groups injected with anti-CJT sera and
      the supernatants of PBMCs compared with control (P > 0.05). (2) Binding of CJT to
      the nerve was found dominant in the sciatic nerves taken from normal rats or
      human either incubated with CJT or in the pathological sciatic nerves induced by
      CJT to various degrees. The binding of CJT to all these nerves was determined.
      (3) After intravenous injection with CJT, no histopathologic change could be
      found in the other viscera of the rats, with the exception of remarkable
      pathological change in peripheral nerves. CONCLUSIONS: (1) CJT could remarkably
      damage the peripheral nerves in rats. Specific pathogenicity of CJT to peripheral
      nerves was well shown, because no histopathologic abnormalities could be found in
      the other viscera, such as brain, liver and kidney etc. although there was
      remarkable pathological change along the peripheral nerve in the animals. (2) No
      immunological pathogenicity of CJT could be demonstrated in the nerves of rats
      after immunization with CJT.

PMID- 14723821
TI  - [Streptococcal toxic shock syndrome in a case].

PMID- 14723822
TI  - [Protective effect and mechanism of pretreatment with curcumin on infectious
      brain edema in rats].
AB  - Curcumin is a natural compound extracted from the spice tumeric, possessing both
      anti-inflammatory antioxidant, and anti-carcinogenic effect, is a potent
      stimulator of the stress-induced expression of heat shock protein 70 kd (HSP70).
      OBJECTIVES: To study the protective effect of pretreatment with curcumin against
      infectious brain edema in rats, and investigate its mechanism by assessing the
      free radical, cytokine and HSP70 expression of the brain. METHODS: An animal
      model of infectious brain edema induced by injecting pertussis bacilli (PB)
      through carotid artery was used. SD rats were randomly divided into five groups:
      (1) Normal control group (NS group, n = 9); (2) Infectious brain edema group (PB
      group, n = 12); (3) DMSO control group (DMSO group, n = 9); (4) HS pretreatment
      group (HS group, n = 9); (5) Curcumin pretreatment group (CUR group, n = 13). The
      water content (WC), Na(+) and K(+) content in brain tissue were measured. The
      content of malondialdehyde (MDA) and super oxide dismitase (SOD) were assessed by
      chemical colorimetry. The levels of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) were detected by ELISA. The HSP70 expression was
      examined by Western blot analysis. RESULTS: (1) The WC and Na(+), MDA, TNF-alpha
      and IL-1beta were increased in PB group compared with NS group (P < 0.01); they
      were decreased in HS and CUR groups compared with PB group (P < 0.01 or P <
      0.05). (2) The content of SOD was decreased in PB group than in NS group (P <
      0.05), and was increased in HS and CUR group Compared with PB group, (P < 0.05).
      (3) Western blot analysis showed that the band density areas of HS, CUR and PB
      groups were higher than those in NS and DMSO groups, especially in CUR group (P <
      0.01). CONCLUSION: Pretreatment with curcumin showed a protective effect against
      infectious brain edema in rats. The effect might be associated with antioxidant,
      inhibition of the activity of cytokines and inducing expression of HSP70 by
      curcumin.

PMID- 14723823
TI  - [Effect of early hemofiltration on endotoxin and cytokines plasma levels of
      endotoxemic pigs].

PMID- 14723824
TI  - [Influence of hypoxia preconditioning on hypoxia-inducible factor- 1alpha in
      hypoxic-ischemic brain damage in the neonatal rat].

PMID- 14723825
TI  - [Infantile tetramine poisoning treated with sodium dimercaptosulfonate: clinical
      analysis of 54 cases].

PMID- 14723826
TI  - [Effect of hemoperfusion on prognosis in dushuqiang (tetramine) poisoning].

PMID- 14723827
TI  - [Monitoring and intervention study of 57,292 perinatal infant congenital
      malformation and death in Jiaxing City].

PMID- 14723828
TI  - [LRP gene expression and its clinical significance in childhood acute leukemia].

PMID- 14723829
TI  - [Treatment of a child with myelodysplastic syndrome by cord blood
      transplantation].

PMID- 14723830
TI  - [Obstructive sleep apnea syndrome in children].

PMID- 14723831
TI  - [A case with neonatal Kawasaki disease].

PMID- 14723832
TI  - Primary Intestinal Lymphangiectasia.
AB  - A high-protein, low-fat diet supplemented with medium chain triglycerides (MCT)
      is the simplest, most effective, and most widely prescribed treatment with the
      fewest side effects. Octreotide has been helpful in cases in which treatment with
      MCT has failed, but it is costly and requires parenteral administration.
      Antiplasmin therapy may have some role when evidence of increased fibrinolysis is
      present. Surgery is reserved for palliation of large ascites or resection of
      isolated lesions.

PMID- 14723833
TI  - Tropical Sprue.
AB  - Tropical sprue is a disease that causes progressive villus atrophy in the small
      intestine, similar to nontropical (celiac) sprue. The loss of intestinal villi
      profoundly affects intestinal absorptive function, and patients with tropical or
      nontropical sprue present with malabsorption. Whereas the etiology of celiac
      sprue has been elucidated in considerable detail, the etiology of tropical sprue
      remains obscure. The favored hypothesis is that the disease is either initiated
      or sustained by a still-undefined infection. Patients with tropical sprue
      typically present with macrocytic anemia due to malabsorption of folate and/or
      vitamin B(12). Treatment of tropical sprue with folic acid replacement was
      introduced more than 50 years ago and has become standard medical treatment.
      Vitamin B(12) replacement is usually added if there is evidence of B(12)
      deficiency or malabsorption. Treatment of tropical sprue with folate and B(12)
      cures the macrocytic anemia and the accompanying glossitis, and often results in
      increased appetite and weight gain. However, even prolonged treatment with these
      vitamins fails to restore villus atrophy, and malabsorption usually persists. The
      benefit of antibiotic treatment of tropical sprue was first documented during
      World War II, when sulfonamides were used to treat epidemics of tropical sprue in
      British and Italian troops in India. Antibiotic treatment has since become the
      standard treatment, and tetracycline has replaced sulfonamides. The recommended
      length of treatment with tetracycline is 6 months and it is given in combination
      with folate. The treatment has been shown to normalize mucosal structure in the
      small intestine and resolve malabsorption in most patients with tropical sprue.
      However, there is a substantial relapse rate in treated patients who return to,
      or remain in, endemic areas in the tropics.

PMID- 14723834
TI  - Gastrointestinal Stromal Tumors Respond to Tyrosine Kinase-targeted Therapy.
AB  - Gastrointestinal stromal tumors (GISTs) are rare tumors of the wall of the
      stomach and small bowel, and also occasionally arise in the mesentery, omentum,
      or retroperitoneum. The incidence of GIST in the United States is approximately
      500 to 750 patients per 100,000 people. GISTs often present late in their
      clinical course unless they are the cause of gastrointestinal bleeding or
      perforation. Surgical resection is the standard of care for primary GIST.
      However, there is a high risk of recurrence in the peritoneum and liver. For
      metastatic GIST, imatinib mesylate is the standard of care. Two phase III studies
      presented in 2003 in abstract form show slightly different results. In the US
      study, 400 mg/d was found to be equivalent to 800 mg/d with respect to response,
      progression-free survival, and overall survival at 12 months. In the
      European/Australasian study, the response rate was the same with either dosage,
      but progression-free survival was better with 800 mg/d compared with 400 mg/d.
      Overall survival data for the latter study were too immature for analysis as of
      May 2003. Adjuvant or neoadjuvant therapy with imatinib is the topic of at least
      three studies through the American College of Surgeons Oncology Group and
      Radiation Therapy Oncology Group and the American College of Radiology Imaging
      Network. Every effort to enroll eligible patients on these studies should be
      made. New treatments for metastatic disease under investigation include a
      tyrosine kinase inhibitor with an expanded panel of targets compared with
      imatinib (SU011248), and the addition of a mammalian target of rapamycin (mTOR)
      inhibitor and the rapamycin derivative RAD001 to imatinib. Given the finding of a
      specific molecular defect to exploit, GISTs have gone from an orphan disease to a
      proving ground for tyrosine kinase-targeted therapy.

PMID- 14723835
TI  - Small Bowel Bacterial Overgrowth: Presentation, Diagnosis, and Treatment.
AB  - Small bowel bacterial overgrowth (SBBO) syndrome is associated with excessive
      numbers of bacteria in the proximal small intestine. The pathology of this
      condition involves competition between the bacteria and the human host for
      ingested nutrients. This competition leads to intraluminal bacterial catabolism
      of nutrients, often with production of toxic metabolites and injury to the
      enterocyte. A complex array of clinical symptoms ensues, resulting in chronic
      diarrhea, steatorrhea, macrocytic anemia, weight loss, and less commonly, protein
      losing enteropathy. Therapy is targeted at correction of underlying small bowel
      abnormalities that predispose to SBBO and appropriate antibiotic therapy. The
      symptoms and signs of SBBO can be reversed with this approach.

PMID- 14723836
TI  - Management of Tracheoesophageal Fistulas in Adults.
AB  - The approach to treatment of adult patients with tracheoesophageal fistulas
      depends on whether the fistula is congenital or acquired in origin. Most adults
      have acquired tracheoesophageal fistulas, and treatment depends on whether the
      fistula is a result of a benign process or a malignancy, with the latter usually
      primary esophageal cancer. For patients with benign tracheoesophageal fistulas,
      treatment is almost always initially supportive followed by definitive surgical
      correction. In general, depending on the size and location of the tracheal aspect
      of the fistula, surgical therapy involves primary repair of the fistula and, if
      necessary, resection and reconstruction of the trachea. For patients with
      malignant tracheoesophageal fistulas, treatment depends on whether the patient is
      resectable and/or medically fit for surgical therapy. However, most patients with
      malignant trach-eoesophageal fistulas have advanced disease and can only be
      treated with palliative measures. The current standard of palliative therapy for
      patients with malignant tracheoesophageal fistulas is the endoscopic or
      radiologic placement of covered self-expanding metallic stents (SEMS), which
      allow closure of the fistula. All three types of commercially available covered
      SEMS have been used in this capacity with success. Other, less common treatment
      options for selected patients with malignant tracheoesophageal fistulas include
      chemotherapy and radiation, surgical bypass, esophageal exclusion, and fistula
      resection and repair.

PMID- 14723837
TI  - Treatment of Epiphrenic and Mid-esophageal Diverticula.
AB  - Thoracic esophageal diverticula are uncommon. They account for less than 30% of
      esophageal diverticula. The majority of patients are asymptomatic or have minimal
      symptoms. About one third of patients present with severe symptoms. Occasionally,
      pulmonary symptoms can be the sole manifestation of the disease and can be life
      threatening. Dysphagia, food regurgitation, chest pain, weight loss, and reflux
      symptoms are the most commonly encountered gastrointestinal symptoms. Malignancy
      is a rare complication of esophageal diverticula; therefore, patients should be
      educated regarding this complication. Appropriate diagnostic tests should be
      arranged promptly if alarming symptoms develop. Esophageal motor disorders are
      found in the majority of patients and need to be taken into account when planning
      therapy. Medical and endoscopic therapies have limited roles in treatment.
      Surgery is the standard of care for patients with pulmonary or incapacitating
      symptoms related to an epiphrenic diverticulum, and myotomy is the cornerstone of
      surgery. To ensure complete relief of the obstruction, the myotomy should extend
      distally at least 1.5 to 2 cm into the stomach and proximally at least to the
      neck of diverticulum. Adding a nonobstructing entireflux procedure is recommended
      to prevent the development of gastroesophageal reflux disease. Occasionally, a
      specific treatment such as a diverticulectomy or diverticulopexy needs to be
      directed to the diverticulum. Preliminary treatment results from minimally
      invasive surgery, especially laparoscopy, have been promising. In the future with
      increased experience, minimally invasive surgery may become the standard of care.

PMID- 14723838
TI  - Duodenogastric Reflux-induced (Alkaline) Esophagitis.
AB  - Duodenogastric reflux is the retrograde flow of duodenal contents into the
      stomach that then mix with acid and pepsin. These agents can reflux into the
      esophagus (ie, duodenogastroesophageal reflux ) and cause gastroesophageal reflux
      disease (GERD) and its complications, including stricture, Barrett's esophagus,
      and adenocarcinoma of the esophagus. Medical and surgical treatments of DGER can
      be difficult. Best medical treatment is proton-pump inhibitors, which decrease
      DGER by inhibiting both gastric acidity and volume, making less gastric contents
      available to reflux into the esophagus. The addition of the gamma-aminobutyric
      (GABA(B)) receptor agonist baclofen may further reduce DGER in patients not
      responding to proton-pump inhibitors. Bile acid-binding agents (aluminum
      containing antacids, cholestyramine, sucralfate, urosodeoxycholic acid) have
      physiologic rationale, but their efficacy is unproven. Prokinetic agents can
      reduce DGER and its upper gastrointestinal symptoms by promoting increased
      gastric emptying. In patients with medically refractory symptoms, a Roux-en-Y
      diversion or duodenal switch operation may be helpful.

PMID- 14723839
TI  - Helicobacter pylori and Gastroesophageal Reflux Disease.
AB  - Since the rediscovery of Helicobacter pylori two decades ago, it has become
      increasingly clear that the true relationships between this organism and diseases
      of the upper gastrointestinal tract are highly complex. H. pylori colonization is
      a strong risk factor for peptic ulceration and distal gastric cancer; however,
      gastritis has no adverse consequences for most hosts, and the prevalence of H.
      pylori is inversely related to gastroesophageal reflux disease (GERD) and its
      sequelae, which include Barrett's esophagus and esophageal adenocarcinoma. One
      clinical implication stemming from these data is that H. pylori eradication may
      not be appropriate in certain human populations due to potential beneficial
      effects conferred by persistent gastric inflammation. However, the majority of
      published intervention trials indicate that H. pylori treatment neither leads to
      the development of clinically significant de novo esophagitis nor exacerbates
      existing reflux disease. Superimposed upon these observations are reports that
      long-term acid suppression induced by proton-pump inhibitors (PPIs) in
      conjunction with H. pylori colonization may enhance the development of atrophic
      gastritis, a well-recognized histologic step in the progression to intestinal
      type gastric cancer. Therefore, current evidence-based recommendations regarding
      management of H. pylori-positive individuals with GERD include the following. H.
      pylori should not be treated with the intent to either improve reflux symptoms or
      prevent the development of reflux complications. However, if patients are to
      receive long-term acid suppressive therapy, they should be tested for H. pylori
      and treated if positive, due to the potential for PPIs to accelerate atrophy
      within H. pylori-infected mucosa. Optimal first-line regimens in this country
      consist of a PPI in combination with clarithromycin and either amoxicillin or
      metronidazole (triple therapy) for at least 7, but preferably 10, days. Because
      the most effective second-line regimens contain metronidazole, it is advisable to
      use amoxicillin instead of metronidazole as first-line therapy in order to
      optimize results should subsequent therapy be required. If first-line regimens
      fail to eliminate H. pylori, patients should receive quadruple therapy consisting
      of a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 14 days. Due
      to the availability and accuracy of noninvasive diagnostic tests for H. pylori,
      it is recommended that successful cure be confirmed after intervention.

PMID- 14723840
TI  - Pill Esophagitis.
AB  - Pill esophagitis is a preventable cause of morbidity. Simple advice on how and
      when to take medication could probably prevent most cases of the illness.
      Avoidance of implicated medications in patients with significant risk factors for
      developing pill esophagitis could prevent additional cases. When the disease
      presents despite these preventive measures, the mainstays of treatment are
      immediate discontinuation of the offending agent and supportive care. If the
      diagnosis is in question, the principle diagnostic modalities are double-contrast
      barium esophagogram and esophagogastroduodenoscopy. Medical management of
      moderate to severe cases includes sucralfate to coat, protect, and promote
      healing of ulcerated esophageal mucosa, and acid-suppressing therapy if
      gastroesophageal reflux disease is felt to have played a role in the pathogenesis
      of the illness. Rare cases may require therapeutic endoscopy or surgical
      intervention early in the disease course. Late complications include esophageal
      strictures that may require therapeutic endoscopy or bougienage.

PMID- 14723841
TI  - Molecular rearrangements within the nuclear pore complexes: a new way to regulate
      nucleocytoplasmic transport.
AB  - Until now, regulation of nucleocytoplasmic transport of macromolecules has been
      thought to occur mainly through modifications of the cargo molecules. However, in
      the December 26 issue of Cell, Makhnevych et al. describe a novel mechanism
      controlling cell cycle progression in yeast that involves subtle molecular
      rearrangements within the nuclear pore complexes.

PMID- 14723842
TI  - DNA segregation by bacterial actin homologs.
AB  - The bacterial actin homolog ParM catalyzes segregation of plasmid DNA in E. coli.
      Recent studies now suggest a model in which ParM forms actin-like filaments
      between two plasmid molecules, thereby providing the driving force for plasmid
      DNA separation.

PMID- 14723843
TI  - A genome analysis of endoreplication in the Drosophila ovary.
AB  - Gene amplification is used by follicle cells to increase the copy number of
      Drosophila chorion genes, which encode structural components of the eggshell. A
      new study by Claycomb et al. in this issue of Developmental Cell raises the
      possibility that gene amplification might also be used for the developmental
      patterning of the egg chamber and oocyte.

PMID- 14723844
TI  - Talking about a revolution: The impact of site-specific recombinases on genetic
      analyses in mice.
AB  - Site-specific recombinase systems (Cre-loxP, Flp-FRT, and phi C31-att) are
      transforming both forward and reverse genetics in mice. By enabling high-fidelity
      DNA modifications to be induced in vitro or in vivo, these systems have incited a
      wave of new biology, advancing our understanding of gene function, genetic
      relationships, development, and disease.

PMID- 14723845
TI  - Polarization of plasma membrane microviscosity during endothelial cell migration.
AB  - Cell movement is characterized by anterior-posterior polarization of multiple
      cell structures. We show here that the plasma membrane is polarized in moving
      endothelial cells (EC); in particular, plasma membrane microviscosity (PMM) is
      increased at the cell leading edge. Our studies indicate that cholesterol has an
      important role in generation of this microviscosity gradient. In vitro studies
      using synthetic lipid vesicles show that membrane microviscosity has a
      substantial and biphasic influence on actin dynamics; a small amount of
      cholesterol increases actin-mediated vesicle deformation, whereas a large amount
      completely inhibits deformation. Experiments in migrating ECs confirm the
      important role of PMM on actin dynamics. Angiogenic growth factor-stimulated
      cells exhibit substantially increased membrane microviscosity at the cell front
      but, unexpectedly, show decreased rates of actin polymerization. Our results
      suggest that increased PMM in lamellipodia may permit more productive actin
      filament and meshwork formation, resulting in enhanced rates of cell movement.

PMID- 14723846
TI  - Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling.
AB  - Despite extensive studies on the anterior-posterior (AP) axis formation of limb
      buds, mechanisms that specify digit identities along the AP axis remain obscure.
      Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3
      specify the digit identities of digits IV and III, respectively. Misexpression of
      Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV
      and digit II to digit III, respectively. Conversely, misexpression of their
      mutants VP16 Delta Tbx2 and VP16 Delta Tbx3 induced anterior transformation. In
      both cases, alterations in the expression of several markers (e.g., BMP2, Shh,
      and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated
      inhibition of interdigital BMP signaling, signaling which is pivotal in
      establishing digit identities. Hence, we conclude that Tbx3 specifies digit III,
      and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the
      interdigital BMP signaling cascade.

PMID- 14723847
TI  - Morphogenetic movements underlying eye field formation require interactions
      between the FGF and ephrinB1 signaling pathways.
AB  - The definitive retinal progenitors of the eye field are specified by
      transcription factors that both promote a retinal fate and control cell movements
      that are critical for eye field formation. However, the molecular signaling
      pathways that regulate these movements are largely undefined. We demonstrate that
      both the FGF and ephrin pathways impact eye field formation. Activating the FGF
      pathway before gastrulation represses cellular movements in the presumptive
      anterior neural plate and prevents cells from expressing a retinal fate,
      independent of mesoderm induction or anterior-posterior patterning. Inhibiting
      the FGF pathway promotes cell dispersal and significantly increases eye field
      contribution. ephrinB1 reverse signaling is required to promote cellular
      movements into the eye field, and can rescue the FGF receptor-induced repression
      of retinal fate. These results indicate that FGF modulation of ephrin signaling
      regulates the positioning of retinal progenitor cells within the definitive eye
      field.

PMID- 14723848
TI  - Drosophila cup is an eIF4E binding protein that associates with Bruno and
      regulates oskar mRNA translation in oogenesis.
AB  - Translational control is a critical process in the spatio-temporal restriction of
      protein production. In Drosophila oogenesis, translational repression of oskar
      (osk) RNA during its localization to the posterior pole of the oocyte is
      essential for embryonic patterning and germ cell formation. This repression is
      mediated by the osk 3' UTR binding protein Bruno (Bru), but the underlying
      mechanism has remained elusive. Here, we report that an ovarian protein, Cup, is
      required to repress precocious osk translation. Cup binds the 5'-cap binding
      translation initiation factor eIF4E through a sequence conserved among eIF4E
      binding proteins. A mutant Cup protein lacking this sequence fails to repress osk
      translation in vivo. Furthermore, Cup interacts with Bru in a yeast two-hybrid
      assay, and the Cup-eIF4E complex associates with Bru in an RNA-independent
      manner. These results suggest that translational repression of osk RNA is
      achieved through a 5'/3' interaction mediated by an eIF4E-Cup-Bru complex.

PMID- 14723849
TI  - The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre
      autophagosomal structure.
AB  - To survive extreme environmental conditions, and in response to certain
      developmental and pathological situations, eukaryotic organisms employ the
      catabolic process of autophagy. Structures targeted for destruction are enwrapped
      by double-membrane vesicles, then delivered into the interior of the
      lysosome/vacuole. Despite the identification of many specific components, the
      molecular mechanism that directs formation of the sequestering vesicles remains
      largely unknown. We analyzed the trafficking of Atg23 and the integral membrane
      protein Atg9 in the yeast Saccharomyces cerevisiae. These components localize
      both to the pre-autophagosomal structure (PAS) and other cytosolic punctate
      compartments. We show that Atg9 and Atg23 cycle through the PAS in a process
      governed by the Atg1-Atg13 signaling complex. Atg1 kinase activity is essential
      only for retrograde transport of Atg23, while recycling of Atg9 requires
      additional factors including Atg18 and Atg2. We postulate that Atg9 employs a
      recycling system mechanistically similar to that used at yeast early and late
      endosomes.

PMID- 14723850
TI  - The POU domain protein spg (pou2/Oct4) is essential for endoderm formation in
      cooperation with the HMG domain protein casanova.
AB  - The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm,
      and endoderm. Zebrafish endoderm differentiation starts with the activation of
      sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm
      formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack
      endodermal precursors. Cell transplantations show that spg acts in early
      endodermal precursors, and cas mRNA-injection into MZspg embryos does not restore
      endoderm development. spg and cas together are both necessary and sufficient to
      activate endoderm development, and stimulate expression of a sox17 promoter
      luciferase reporter. Endoderm and mesoderm derive from a common origin,
      mesendoderm. We propose that Spg and Cas commit mesendodermal precursors to an
      endodermal fate. The joint control of endoderm formation by spg and cas suggests
      that the endodermal germlayer may be a tissue unit with distinct genetic control,
      thus adding genetic support to the germlayer concept in metazoan development.

PMID- 14723851
TI  - All mouse ventral spinal cord patterning by hedgehog is Gli dependent and
      involves an activator function of Gli3.
AB  - An important question is how the gradient of Hedgehog is interpreted by cells at
      the level of the Gli transcription factors. The full range of Gli activity and
      its dependence on Hh have not been determined, although the Gli2 activator and
      Gli3 repressor have been implicated. Using the spinal cord as a model system, we
      demonstrate that Gli3 can transduce Hedgehog signaling as an activator. All
      expression of the Hh target gene Gli1 is dependent on both Gli2 and Gli3. Unlike
      Gli2, however, Gli3 requires endogenous Gli1 for induction of floor plate and V3
      interneurons. Strikingly, embryos lacking all Gli function develop motor neurons
      and three ventral interneuron subtypes, similar to embryos lacking Hh signaling
      and Gli3. Therefore, in the spinal cord all Hh signaling is Gli dependent.
      Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron
      development and spatial patterning of ventral spinal cord progenitors.

PMID- 14723852
TI  - Dynamics of global gene expression changes during mouse preimplantation
      development.
AB  - Understanding preimplantation development is important both for basic
      reproductive biology and for practical applications including regenerative
      medicine and livestock breeding. Global expression profiles revealed and
      characterized the distinctive patterns of maternal RNA degradation and zygotic
      gene activation, including two major transient waves of de novo transcription.
      The first wave corresponds to zygotic genome activation (ZGA); the second wave,
      named mid-preimplantation gene activation (MGA), precedes the dynamic
      morphological and functional changes from the morula to blastocyst stage. Further
      expression profiling of embryos treated with inhibitors of transcription,
      translation, and DNA replication revealed that the translation of maternal RNAs
      is required for the initiation of ZGA. We propose a cascade of gene activation
      from maternal RNA/protein sets to ZGA gene sets and thence to MGA gene sets. The
      large number of genes identified as involved in each phase is a first step toward
      analysis of the complex gene regulatory networks.

PMID- 14723853
TI  - A genome-wide study of gene activity reveals developmental signaling pathways in
      the preimplantation mouse embryo.
AB  - The preimplantation development of the mammalian embryo encompasses a series of
      critical events: the transition from oocyte to embryo, the first cell divisions,
      the establishment of cellular contacts, the first lineage differentiation-all the
      first subtle steps toward a future body plan. Here, we use microarrays to explore
      gene activity during preimplantation development. We reveal robust and dynamic
      patterns of stage-specific gene activity that fall into two major phases, one up
      to the 2-cell stage (oocyte-to-embryo transition) and one after the 4-cell stage
      (cellular differentiation). The mouse oocyte and early embryo express components
      of multiple signaling pathways including those downstream of Wnt, BMP, and Notch,
      indicating that conserved regulators of cell fate and pattern formation are
      likely to function at the earliest embryonic stages. Overall, these data provide
      a detailed temporal profile of gene expression that reveals the richness of
      signaling processes in early mammalian development.

PMID- 14723854
TI  - Gene amplification as a developmental strategy: isolation of two developmental
      amplicons in Drosophila.
AB  - Gene amplification is known to be critical for upregulating gene expression in a
      few cases, but the extent to which amplification is utilized in the development
      of diverse organisms remains unknown. By quantifying genomic DNA hybridization to
      microarrays to assay gene copy number, we identified two additional developmental
      amplicons in the follicle cells of the Drosophila ovary. Both amplicons contain
      genes which, following their amplification, are expressed in the follicle cells,
      and the expression of three of these genes becomes restricted to specialized
      follicle cells late in differentiation. Genetic analysis establishes that at
      least one of these genes, yellow-g, is critical for follicle cell function,
      because mutations in yellow-g disrupt eggshell integrity. Thus, during follicle
      cell differentiation the entire genome is overreplicated as the cells become
      polyploid, and subsequently specific genomic intervals are overreplicated to
      facilitate gene expression.

PMID- 14723856
TI  - Rehabilitation of pelvic floor muscles utilizing trunk stabilization.
AB  - The pelvic floor muscles (PFM) are part of the trunk stability mechanism. Their
      function is interdependent with other muscles of this system. They also
      contribute to continence, elimination, sexual arousal and intra-abdominal
      pressure. This paper outlines some aspects of function and dysfunction of the PFM
      complex and describes the contribution of other trunk muscles to these processes.
      Muscle pathophysiology of stress urinary incontinence (SUI) is described in
      detail. The innovative rehabilitation programme for SUI presented here utilizes
      abdominal muscle action to initiate tonic PFM activity. Abdominal muscle activity
      is then used in PFM strengthening, motor relearning for functional expiratory
      actions and finally impact training.

PMID- 14723857
TI  - Doppler studies evaluating the effect of a physical therapy screening protocol on
      vertebral artery blood flow.
AB  - General and isolated cervical positional tests are used to screen for potential
      vertebro-basilar insufficiency (VBI). There is limited research evaluating
      vertebral artery blood flow in these positions to justify the rationale of
      progressive mechanical stress occurring to the arteries. The purpose of the study
      was to determine vertebral artery blood flow in six cervical positions used in
      clinical practice. A comprehensive cervical assessment was conducted on 22 men
      and women (mean age 35) with no known vascular pathology. Vertebral artery peak
      systolic (PS), end diastolic (ED) flow rates and resistive index (RI) were
      measured using duplex colour Doppler sonography (sampling at C3-C5) in neutral,
      rotation, extension, combined rotation-extension, combined rotation-extension
      traction, deKelyn's position and a C1-C2 pre-manipulative hold. Results showed
      there was a significant decrease in PS and ED in the contra-lateral artery during
      the pre-manipulative hold, and a decrease in ED in the contra-lateral artery
      during rotation. There was no effect of age, gender or mobility restriction on
      these blood flow changes. The pre-manipulative hold had the greatest response
      with 34% of the arteries demonstrating a complete cessation of ED flow. In
      conclusion the pre-manipulative hold and rotation created the greatest mechanical
      stress to the contra-lateral vertebral artery. These two positions may be useful
      screening positions to identify individuals at risk for VBI due to inadequate
      collateral blood flow.

PMID- 14723858
TI  - Inter- and intraexaminer reliability in palpation of the "primary respiratory
      mechanism" within the "cranial concept".
AB  - Inevitable subjectivity makes interexaminer reliability of manual assessment
      procedures a special matter of concern. The cranial concept (CC), one aspect of
      osteopathy, deals with very subtle changes that have to be palpated. One of the
      main principles of the CC is the primary respiratory mechanism (PRM), which is
      hypothesized to be a palpable physiological phenomenon that occurs in rhythmic
      cycles, called flexion- and extension-phase, which are independent from cardiac
      and respiratory rates. Palpation of the PRM is one of the first steps in
      assessment within the CC. An inter- and intraexaminer reliability study design
      for repeated measures was used in this study. Forty nine healthy subjects were
      palpated simultaneously twice, once at the head and once at the pelvis. PRM
      frequency (f), the mean duration of the flexion phase and the mean ratio of
      flexion- to extension-phase were used as the main outcome measures. Inter- and
      intraexaminer reliability and correlations to the respiratory rates were analysed
      for all three parameters. Inter- as well as intraexaminer agreement could not be
      described beyond chance agreement, as the range within the 95% limits of
      agreement (e.g. for f=6.6 cycles/90 s) for all cases resembled the total range of
      values (e.g. for f=7 cycles/90 s) that were produced. A significant effect of the
      examiners' respiration was found for both examiners at the pelvis (P=0.004 for
      one examiner, P <0.0001 for the other examiner), and for one examiner only at the
      head (P=0.0017). No correlation could be found for the subjects' respiratory
      rates. In conclusion, PRM-rates could not be palpated reliably and under certain
      conditions were influenced by the examiners' respiratory rates. These results do
      not support the hypotheses behind the PRM. The role of PRM palpation for clinical
      decision making and the models explaining the PRM should therefore be rethought.

PMID- 14723859
TI  - Long-term follow-up of patients with low back pain attending for manipulative
      care: outcomes and predictors.
AB  - Psychosocial factors are known to act as obstacles to recovery from low back
      pain, but predictors of longer-term outcomes are not established. An average 4
      year follow-up of a cohort of 252 low back pain patients attending for
      manipulative care was conducted to describe the longer-term course of low back
      pain, and to identify predictors of outcomes. Clinical and psychosocial data were
      obtained at baseline. Mailed questionnaires collected self-reported outcomes
      (pain, disability, recurrence and care seeking). Among the 60% who responded, the
      statistically significant reduction in mean Roland Disability Questionnaire score
      seen at 1 year did not improve further during follow-up. At the 4-year point, 49%
      of respondents reported residual disability, and 59% reported at least 'mild'
      pain. Symptom recurrence beyond the 1-year point was reported by 78% of
      respondents, with half of them seeking further care. Recurrence and care seeking
      were related to fear avoidance beliefs and duration of presenting symptoms. The
      disability score at 4-years was statistically significantly related to baseline
      depressive symptoms and higher pain intensity. Low back pain presenting for
      manipulative care is characterized by high levels of recurrence and care seeking
      over at least 4-years for many patients. Because psychosocial factors at
      presentation exert a long-term influence, they need to be considered by manual
      therapists.

PMID- 14723860
TI  - Referencing and quotation accuracy in four manual therapy journals.
AB  - The aim of the study was to investigate the reference and quotation accuracy in
      four peer-reviewed manual therapy journals. A stratified random sample of
      original research (n=7) was collected from each of the journals spanning the
      years January 2000 to December 2001. A further random selection of 80 references
      from each journal paper sampled was then reviewed (Total N=320) for citation and
      quotation accuracy. Numbers of citations with errors were determined, then
      classified as either major or minor and categorized by bibliographic headings
      (author, title, journal, year, volume, page and irretrievable). Each quotation
      was individually assessed for accuracy and judged to be either correct or
      incorrect. A quotation was deemed correct if it accurately substantiated and
      reported the original authors assertions. One hundred and fifteen citations
      across all journals contained errors (35.9%). Some citations exhibited multiple
      major and minor errors. Bibliographically classified errors for all journals
      showed 61 author, 51 title, 6 journal, 4 year, 12 volume and 25 page errors. JMPT
      showed the lowest referencing error rate (20%) while JBWMT recorded the highest
      (58.8%). The total number of quotation errors across all journals was 69 (12.3%).
      JMPT showed the lowest quotation error rate of 6 (4.7%), MT had 12 errors (7.3%),
      JOM produced 21 errors (13.3%), while JBWMT recorded the highest error rate with
      32 (27.6%). Poor citation and quotation is a reflection on the scholarly work of
      the authors and the journal. The trend for errors in quotation is more worrying
      than citation errors as it reflects poor diligence on the part of the
      investigators.

PMID- 14723861
TI  - Measurement of abdominal muscle thickness using M-mode ultrasound imaging during
      functional activities.
AB  - Ultrasound imaging has been previously utilized in the measurement of muscle
      thickness and cross-sectional area in research studies, and advocated as a
      clinical biofeedback tool in the rehabilitation of transversus abdominis function
      following episodes of low back pain. This paper describes how the thickness of
      the abdominal muscles can be quantified with a new measurement technique using M
      mode ultrasound. The technique uses a custom-made transducer holder that
      facilitates measurement of muscle thickness changes during functional activity.
      Limitations of the technique and potential future applications are discussed. The
      M-mode ultrasound technique may provide an effective method for the non-invasive
      measurement of abdominal muscle thickness during functional activities.

PMID- 14723862
TI  - Statistics and pain-related fear measures in acute low back pain.

PMID- 14723868
TI  - Magnetic resonance evaluation of the interrelationship between articular
      cartilage and trabecular bone of the osteoarthritic knee.
AB  - OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to determine
      the relationship between articular cartilage degeneration and trabecular bone
      changes of the femur, condyles and tibia in human knees with osteoarthritis (OA).
      METHODS: Subjects were divided into three groups: without OA (OA0), mild OA (OA1)
      and severe OA (OA2). Sagittal images of the knee (0.234 x 0.234mm2, 2-mm slice
      thickness) were obtained at 1.5T and used for calculating the volume and
      thickness of the femoral and tibial cartilage. Axial images (0.195 x 0.195mm2, 1
      mm slice thickness) were used for calculating the trabecular bone structure
      parameters: apparent bone volume fraction, trabecular number, trabecular
      separation and trabecular thickness. RESULTS: Cartilage volume and thickness were
      less in patients with OA compared to normal controls (P<0.1). Articular cartilage
      thinning is associated with bone structure loss in the opposite femoral condyle
      (P<0.05). In varus OA, there were extensive correlations between medial tibia and
      medial femoral cartilage degeneration, and loss of bone structure in the lateral
      tibia and lateral condyle. Additional correlations existed between the
      compartmental differences (lateral minus medial) of cartilage thickness and bone
      structure. CONCLUSION: Degradation of articular cartilage within a compartment
      correlates with a loss of bone structure in the opposite compartment. The
      correlation between the (L-M) differences corroborates this relationship.
      Malalignment of the knee due to cartilage degeneration is associated with bone
      formation in the diseased condyle and bone resorption in the opposite
      compartment.

PMID- 14723869
TI  - X-ray detection of structural orientation in human articular cartilage.
AB  - OBJECTIVE: To determine the feasibility of detecting the structural orientation
      in cartilage with Diffraction Enhanced X-Ray Imaging. DESIGN: Human tali and
      femoral head specimens were Diffraction Enhanced X-Ray Imaged (DEI) at the SYRMEP
      beamline at Elettra at various energy levels to detect the architectural
      arrangement of collagen within cartilage. DEI utilizes a monochromatic and highly
      collimated beam, with an analyzer crystal that selectively weights out photons
      according to the angle they have been deviated with respect to the original
      direction. This provides images of very high contrast, and with the rejection of
      X-ray scatter. RESULTS: DEI allowed the visualization of articular cartilage and
      a structural orientation, resembling arcades, within. CONCLUSION: Our diffraction
      enhanced images represent the first radiographic detection of the structural
      orientation in cartilage. Our data are in line with previous studies on the
      structural organization of joint cartilage. They confirm the model of a vaulting
      system of collagen fiber bundles interrupted by proteoglycan aggregates.

PMID- 14723870
TI  - The cellular responses of articular cartilage to sharp and blunt trauma.
AB  - OBJECTIVE: To determine the response of immature articular cartilage to both
      sharp and blunt trauma in terms of cell death, cell proliferation and matrix
      synthesis. DESIGN: Blunt wounds were made with a trephine in full depth immature
      bovine articular cartilage explants which were cut in half through the center of
      the trephine wound with a sharp scalpel to produce blunt and sharp trauma on the
      same explant. Explants were maintained in culture for up to 10 days. Prior to
      fixation at days 2, 5 and 10, medium was supplemented with 10 microCi ml-1 35S
      sulphate, [3H]-proline or [3H]-thymidine for 24h to assess matrix synthesis and
      cell proliferation. Cell death was assessed using a Live/Dead label. RESULTS: In
      the case of blunt wounds, a band of cell death was observed adjacent to the
      lesion edge. Microautoradiography demonstrated little radiolabel incorporation
      and, therefore, no new matrix synthesis or cell proliferation within this region.
      In contrast, wounds made with a sharp scalpel showed restricted cell death, with
      radiolabel incorporation adjacent to the lesion edge at all time points. This
      demonstrated not only chondrocyte proliferation and new matrix synthesis at the
      wound margin, but also an up-regulation of matrix synthesis adjacent to the
      lesion edge. CONCLUSIONS: In terms of clinical relevance, the use of sharp
      precise instruments during the surgical management of cartilage defects may be
      necessary to reduce cell death and promote matrix elaboration at the lesion edge
      in order to facilitate successful integration.

PMID- 14723871
TI  - Dynamic compression of chondrocyte-seeded fibrin gels: effects on matrix
      accumulation and mechanical stiffness.
AB  - OBJECTIVE: Various strategies have been tested to direct and control matrix
      synthesis in tissue engineered cartilage, including mechanical stimulation of the
      construct both before and after implantation. This study examined the effects of
      oscillatory compression on chondrocytes in a fibrin-based tissue engineered
      cartilage. DESIGN: Chondrocyte-seeded fibrin gels were cultured under unconfined
      mechanical compression for 10 or 20 days (free-swelling, 10% static, or 10+/-4%
      at 0.1 or 1Hz). During the culture period, accumulation of nitrite, sGAG, and
      proteolytic enzymes in the culture media were monitored. Following culture, the
      mechanical stiffness and biochemical content of the gels (DNA, sGAG, and
      hydroxyproline content and GAG Delta-disaccharide composition) were assessed.
      RESULTS: Compared to free-swelling conditions, static compression had little
      effect on the mechanical stiffness or biochemical content of the gels. Compared
      to static compression, oscillatory compression produced softer gels, inhibited
      sGAG and hydroxyproline accumulation in the gels, and stimulated accumulation of
      nitrite and sGAG in the culture media. Minimal differences were observed in DNA
      content and Delta-disaccharide composition across treatment conditions.
      CONCLUSIONS: In this study, oscillatory compression inhibited formation of
      cartilage-like tissues by chondrocytes in fibrin gels. These results suggest that
      the effects of mechanical stimuli on tissue engineered cartilage may vary
      substantially between different scaffold systems.

PMID- 14723872
TI  - Chondrocyte death during murine osteoarthritis.
AB  - OBJECTIVE: To determine whether chondrocyte apoptosis occurs during the
      progression of osteoarthritis (OA) in the STR/ort mouse model of OA. METHODS:
      Serial cryostat sections were cut (10 microns) through the knee joint of young
      and old male STR/ort mice and graded for the severity of OA lesions. Age- and sex
      matched CBA mice were used as controls. Apoptotic chondrocytes were detected
      using the TUNEL assay. Ultrastructural changes were examined using electron
      microscopy (EM). Expression of biochemical markers associated with apoptosis
      (bax, bcl-2 and caspases-3, -8 & -9) was investigated using immunohistochemistry.
      RESULTS: TUNEL assays on histological sections of STR/ort knee joints showed that
      the number of TUNEL-positive chondrocytes in the tibial medial articular
      cartilage correlated with the severity of the OA damage. These cells were located
      close to the lesional area. Only very occasional TUNEL positive chondrocytes were
      detected in either morphologically normal STR/ort cartilage or in control CBA
      cartilage. Ultrastructural analysis of chondrocytes neighboring focal
      osteoarthritic lesions in STR/ort tibial cartilage revealed an abundance of
      abnormal cells exhibiting numerous morphological changes. These resembled, but in
      some cases differed, from changes reported in classical apoptosis. The changes
      include abnormal distribution of chromatin, cell shrinkage, membrane blebbing and
      deposition of cell remnants (apoptotic bodies) in the lacuna space. Despite the
      TUNEL and EM changes, immunohistochemistry failed to detect any changes in the
      ratio of bax to bcl-2 in tibial chondrocytes of STR/ort mice. Both bcl-2 and bax
      levels decreased with age in morphologically normal STR/ort and control CBA
      cartilage. None of the caspases tested for was detected in tibial chondrocytes of
      either strain. CONCLUSION: Chondrocyte cell death is correlated with the
      progression of OA in STR/ort mice and has many of the morphological
      characteristics of classical apoptosis. Absence of changes in bax to bcl-2 ratio
      in STR/ort chondrocytes indicate that the mitochondrial pathway of apoptosis is
      unlikely to be involved. Failure to detect caspases could be due to low levels of
      enzyme expression, expression within a very brief time period, or to a caspase
      independent mechanism of cell death.

PMID- 14723873
TI  - TSG-6 and calcium ions are essential for the coupling of inter-alpha-trypsin
      inhibitor to hyaluronan in human synovial fluid.
AB  - OBJECTIVE: To investigate the role of tumor necrosis factor stimulated gene 6
      (TSG-6) and metal ions in the coupling of inter-alpha-trypsin inhibitor (ITI) to
      hyaluronan in human synovial fluid. DESIGN: The concentration of ITI heavy chains
      bound to hyaluronan was determined by a two-step electrophoretic technique.
      Synovial fluid, TSG-6 depleted synovial fluid and metal chelated synovial fluid
      were tested for their ability to support the coupling of ITI heavy chains to
      hyaluronan. RESULTS: When synovial fluid was mixed with an ITI-source (serum or
      purified ITI), coupling of ITI heavy chains to hyaluronan took place. TSG-6
      immunodepleated synovial fluid lost the coupling activity, but addition of
      recombinant TSG-6 restored the activity. EDTA inhibited the coupling activity,
      but combinations of the metal-ion chelators Mg-EGTA and Ca-EGTA demonstrated,
      that Ca++ is essential for the coupling of ITI heavy chains to hyaluronan.
      CONCLUSIONS: Tumor necrosis factor stimulated gene 6 (TSG-6) and calcium ions are
      both essential for the coupling of inter-alpha-trypsin inhibitor to hyaluronan in
      human synovial fluid.

PMID- 14723874
TI  - Fibronectin fragments cause release and degradation of collagen-binding molecules
      from equine explant cultures.
AB  - OBJECTIVE: Previous experiments have shown that addition of fragmented
      fibronectin can induce cartilage chondrolysis. In this study we investigated the
      fate of the collagen- and cell-binding molecules Cartilage oligomeric matrix
      protein (COMP) and chondroadherin. DESIGN: Equine articular cartilage explants
      were stimulated with the C-terminal and the N-terminal heparin-binding fragments
      of fibronectin respectively, and the conditioned media were analysed by both
      quantitative (ELISA) and qualitative (mass spectrometry, Western blots) methods.
      RESULTS: Both COMP and chondroadherin were released in a dose-dependent manner
      upon stimulation with the Hep II (C-terminal heparin-binding) fragment of
      fibronectin. The kinetics of release for the two components differed. Moreover,
      COMP was degraded while no fragments of chondroadherin could be detected.
      Stimulation with Hep II also induced production of nitric oxide in a dose
      dependent manner. We compared effects of the Hep II fragment with that of Hep I
      (the N-terminal heparin-binding fragment of fibronectin) and found that while Hep
      I did indeed elicit release of COMP and chondroadherin, the response was less
      potent, and production of nitric oxide was negligible. The responses to both
      fragments were elicited within 24h. CONCLUSIONS: We suggest that the events
      described here may be early, critical stages in cartilage destruction preceding
      collagen destruction.

PMID- 14723875
TI  - Effects of long-term estrogen replacement therapy on articular cartilage IGFBP-2,
      IGFBP-3, collagen and proteoglycan levels in ovariectomized cynomolgus monkeys.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of long-term
      estrogen replacement therapy (ERT) on insulin-like growth factor binding protein
      (IGFBP)-2, IGFBP-3, collagen and proteoglycan levels in the articular cartilage
      of the knee joint in a well-characterized monkey model of naturally occurring
      osteoarthritis (OA). A secondary aim was to evaluate the effect of soy
      phytoestrogen treatment on these articular cartilage components. DESIGN: Monkeys
      were ovariectomized and given ERT, soy phytoestrogen treatment or no treatment
      (control) for 3 years. Ten animals were randomly selected from each of the three
      groups and the cartilage was dissected from the proximal tibia and distal femur
      of the knee. Levels of IGFBP-2, IGFBP-3, and total protein were measured in
      cartilage desorptions, and proteoglycan levels and collagen levels were measured
      in the cartilage tissue. Sections from the tibial plateau of the opposite knee
      were immunostained using antibodies directed against IGFBPs and evaluated
      subjectively. RESULTS: IGFBP-3 levels were significantly higher, and total
      protein levels were significantly lower in the cartilage desorption samples from
      the estrogen-treated animals compared to the control animals. There were no
      significant differences in IGFBP-2, collagen or proteoglycan levels between the
      estrogen-treated and control groups. Soy phytoestrogen treatment had no
      significant effect on the levels of any of the cartilage components that were
      measured. The staining patterns observed by immunohistochemistry suggested local
      production of IGFBP-2 and IGFBP-3 by articular cartilage chondrocytes.
      CONCLUSIONS: Long-term estrogen treatment results in increased IGFBP-3 levels in
      articular cartilage without a significant change in IGFBP-2, collagen or
      proteoglycan content, and IGFBP-3 appears to be synthesized by articular
      cartilage chondrocytes. Long-term soy phytoestrogen treatment did not have a
      statistically significant effect on the levels of IGFBP-2, IGFBP-3, collagen or
      proteoglycan.

PMID- 14723876
TI  - Early radiographic osteoarthritis is associated with substantial changes in
      cartilage volume and tibial bone surface area in both males and females.
AB  - OBJECTIVE: To describe the association between early radiographic osteoarthritis
      of the knee (ROA), knee cartilage volume and tibial bone surface area. METHODS:
      Cross-sectional convenience sample of 372 male and female subjects (mean age 45
      years, range 26-61). Articular cartilage volume, bone area and volume were
      determined at the patella, medial tibial and lateral tibial compartments by
      processing images acquired in the sagittal plane using T1-weighted fat saturation
      MRI. ROA was assessed with a standing semiflexed radiograph and the OARSI atlas
      for joint space narrowing and osteophytosis. Both radiographs and MRIs were
      performed in the right knee and read by different observers. RESULTS: ROA
      (predominantly grade 1) was present in 17% of subjects of which medial joint
      space narrowing was most common (14%) followed by medial osteophytes (6%). Grade
      one medial joint space narrowing was associated with substantial reductions in
      cartilage volume at both the medial and lateral tibial and patellar sites within
      the knee (adjusted mean difference 11-13%, all P<0.001) while grade one
      osteophytosis was associated with substantial increases in both lateral and
      medial tibial joint surface area (adjusted mean difference 10-16%, all P<0.001).
      In contrast, osteophytosis was not associated with a significant change in
      cartilage volume and joint space narrowing was not associated with a significant
      change in tibial bone area (all P>0.05). CONCLUSIONS: Early medial compartment
      ROA is associated with substantial reductions in cartilage volume and increases
      in bone area. These large changes, when combined with similar measurement error
      for MRI and radiographs, suggest that MRI may be superior at detecting and hence
      understanding early osteoarthritis of the knee in humans.

PMID- 14723877
TI  - Characterization of melatonin binding sites in the brain and retina of the frog
      Rana perezi.
AB  - The aim of this study was to characterize 2-[125I]iodomelatonin binding sites in
      the neural retina and central nervous system (telencephalon, diencephalon, and
      optic tectum) of the anuran amphibian Rana perezi. Saturation and kinetic studies
      and pharmacological characterization revealed the existence of a unique melatonin
      binding site that belongs to the Mel 1 receptor subtype. The affinity of this
      site is similar in all tissues studied (Kd, 10.5-12.8 pM), but the density varied
      from diencephalon and optic tectum, which exhibit the highest density, to
      telencephalon with the lowest. Neural retina showed an intermediate receptor
      density. This melatonin-binding site fulfills the requirements of a real hormone
      receptor; the binding is saturable, reversible, and inhibited by different
      melatonin agonists and antagonists. The affinity order of ligands is: 2-phenyl
      melatonin = 2-I-melatonin > 6-Cl-melatonin = melatoninz >> luzindole.
      Additionally, specific binding is decreased by non-hydrolysable GTP analogue,
      sodium, and by pretreatment of membranes with pertussis toxin. All these results
      suggest the existence of a widely distributed and pharmacologically homogeneous
      melatonin receptor of the subfamily Mel 1 in the nervous system of Rana perezi
      coupled to a Gi/o protein.

PMID- 14723878
TI  - Development and validation of a radioimmunoassay for fish insulin-like growth
      factor I (IGF-I) and the effect of aquaculture related stressors on circulating
      IGF-I levels.
AB  - This paper describes the development and validation of a commercially available
      radioimmunoassay (RIA) for the detection of fish insulin-like growth factor-I
      (IGF-I). The assay was developed using recombinant barramundi IGF-I as antigen
      and recombinant tuna IGF-I as radiolabelled tracer and standard. Assay
      sensitivity was 0.15 ng/ml, inter-assay variation was 16% (n = 9) and intra-assay
      variation was 3% (n = 10). Cross reactivity of less than 0.01% was found with
      salmon insulin, salmon IGF-II and barramundi IGF-II, less than 0.5% with human
      IGF-I and less than 1% with human IGF-II. Parallel dose-response inhibition
      curves were shown for barramundi (Lates calcarifer), coho salmon (Oncorhynchus
      kisutch), Southern Bluefin tuna (Thunnus maccoyii), tilapia (Oreochromis
      mossambicus), and seabream (Pagrus auratus) IGF-I. The assay was then used to
      measure stress related changes in different aquacultured fish species. Salt water
      acclimated Atlantic salmon smolts (Salmo salar) bathed for 2 h in fresh water
      showed significantly lower IGF-I concentrations than control smolts two days
      after the bath (53.1 compared to 32.1 ng/ml), with levels of IGF-I also lower in
      smolts exhibiting stunted growth (stunts). Capture and confinement of wild tuna
      in sea-cages resulted in a significant decrease in IGF-I levels (28 ng/ml) when
      compared to tuna captured and sampled immediately (48 ng/ml), but had recovered
      to starting levels after 3 weeks (43 ng/ml). Handling and isolation in silver
      perch (Bidyanus bidyanus) led to a gradual decline in IGF-I over a 12 h period
      (36-19 ng/ml) but showed signs of recovery by 24 h (24 ng/ml) and had recovered
      fully 72 h after treatment (40 ng/ml). A similar trial in black bream
      (Acanthopagrus butcherii) showed comparable results with IGF-I levels gradually
      decreasing (40-26 ng/ml) over 24 h, results that were mirrored by cortisol
      concentrations which increased during this time (1-26 ng/ml). In the studies
      presented here changes in IGF-I levels were not observed for at least 3 h after
      exposure to the stressor. We suggest this is due to the endocrine nature of IGF-I
      regulation and the clearance rate of IGF-I in vivo.

PMID- 14723879
TI  - Regulation of Arctic char (Salvelinus alpinus) egg shell proteins and
      vitellogenin during reproduction and in response to 17beta-estradiol and
      cortisol.
AB  - Estrogens induce both vitellogenin (Vtg) and egg shell (zona pellucida; ZP)
      protein synthesis in salmonids. However, while Vtg is strictly under estrogenic
      control, recent reports suggest that additional mechanisms are involved in ZP
      protein synthesis. During sexual maturation both estrogen and glucocorticoid
      levels increase in the circulation of female fish. As glucocorticoids have been
      shown to interfere with Vtg induction in fish we investigated whether cortisol
      (F) had similar effects on ZP regulation. In the present study we determined both
      the natural variation in Vtg and ZP during an annual reproductive cycle in female
      Arctic char (Salvelinus alpinus), and the effect of co-treatment of juvenile
      Arctic char with 17beta-estradiol (E2) and F. During sexual maturation the
      expression of Vtg and ZP correlated to plasma levels of E2 and F. Determination
      of Vtg and ZP protein levels following co-treatment with E2 and F showed that F
      antagonized E2 induction of Vtg. However, F was observed to potentiate the
      expression of ZP protein in the same fish. These results indicate that in Arctic
      char Vtg and ZP proteins are not regulated by the same mechanisms and suggest
      that ZP protein expression does not necessarily imply exposure to estrogenic
      compounds alone, and may thus not be ideally suited as a biomarker of exposure to
      estrogenic compounds.

PMID- 14723880
TI  - Identification of angiotensin I in several vertebrate species: its structural and
      functional evolution.
AB  - In order to delineate further the molecular evolution of the renin-angiotensin
      system in vertebrates, angiotensin I (ANG I) has been isolated after incubation
      of plasma and kidney extracts of emu (Dromiceus novaehollandiae), axolotl
      (Ambystoma mexicanum), and sea lamprey (Petromyzon marinus). The identified
      sequences were [Asp1, Val5, Asn9] ANG I in emu, [Asp1, Val5, His9] ANG I in
      axolotl, and [Asn1, Val5, Thr9] ANG I in sea lamprey. These results confirmed the
      previous findings that tetrapods have Asp and fishes including cyclostomes have
      Asn at the N-terminus, and that the amino acid residue at position 9 of ANG I was
      highly variable but, those at other positions were well conserved among different
      species. Since Asp and Asn are convertible during incubation, angiotensinogen
      sequences were searched in the genome and/or EST database to determine the N
      terminal amino acid residue from the gene. The screening detected 12 tetrapod (10
      mammalian, one avian, and one amphibian) and seven teleostean angiotensinogen
      sequences. Among them, all tetrapods have [Asp1] ANG except for Xenopus, and all
      teleosts have [Asn1] ANG, thereby confirming the above rule. Comparison of the
      vasopressor activity in the eel revealed that [Asn1] ANG I and II were more
      potent than [Asp1] peptides, which was opposite to the previous results in
      mammals and birds, in which [Asp1] ANG I and II were more potent. Collectively,
      the present results support the general rule that tetrapods have [Asp1] ANG and
      fishes including cyclostomes have [Asn1] ANG. However, an aquatic anuran
      (Xenopus) has [Asn1] ANG in its gene despite another aquatic urodele (axolotl)
      has [Asp1] ANG. From the functional viewpoint, homologous [Asn1] ANG was more
      potent in fish as is homologous [Asp1] ANG in tetrapods, suggesting that ANG II
      molecule has undergone co-evolution with its receptor during vertebrate
      phylogeny.

PMID- 14723881
TI  - Glucocorticoid-induced thymocyte apoptosis in wall lizard Hemidactylus
      flaviviridis.
AB  - The aim of the present study is to demonstrate the phenomenon and mechanism of GC
      induced cell death of thymocytes in wall lizard Hemidactylus flaviviridis. Lizard
      thymocytes were treated in vitro with different concentration of corticosterone
      (CS) for varying durations and the genomic DNA was analyzed both by agarose gel
      electrophoresis and flow cytometry. Corticosterone induced DNA fragmentation in a
      dose-dependent manner, as the DNA laddering was more prominent at 10(-14) M than
      at lower concentrations. However, CS could activate the programmed cell death of
      thymocytes only when incubated for 48 h and not at 3, 6, 12, or 24 h. Similar
      results were obtained following the flow cytometric analysis. The highest
      apoptotic cell death was noted at 10(-14) M concentration. CS-induced programmed
      cell death was decreased dramatically when the thymocytes were preincubated with
      RU 486 (10(-9) ng /ml) for 24 h, suggesting the classical receptor-mediated
      genomic pathway of glucocorticoid action in inducing apoptosis of thymocytes in
      wall lizard H. flaviviridis.

PMID- 14723882
TI  - Variation in vasotocin immunoreactivity in the brain of recently isolated
      populations of a death valley pupfish, Cyprinodon nevadensis.
AB  - Pupfishes in the Death Valley region of California and Nevada comprise a
      monophyletic group of populations that became isolated in remote streams and
      springs over the past 20,000 years. These aquatic habitats show considerable
      ecological diversity, and allopatric populations have evolved differences in
      morphology and behavior. Here we investigated whether the divergence of pupfish
      populations in Death Valley might be associated with changes in arginine
      vasotocin (AVT). We used immunocytochemistry to compare the expression of AVT in
      the brain of Amargosa pupfish (Cyprinodon nevadensis) from two Death Valley
      populations: (1) the Amargosa River-a highly variable desert stream containing
      the Cyprinodon nevadensis amargosae subspecies, and (2) Big Spring-a
      comparatively stable springhead and outflow inhabited by Cyprinodon nevadensis
      mionectes. These particular populations have been isolated from each other for
      only 400-4000 years. In both populations AVT-immunoreactive somata localized to
      parvocellular and magnocellular neurons in the preoptic area, with AVT
      immunoreactive fibers extending ventrolaterally to innervate the pituitary. We
      found that both parvocellular and magnocellular AVT-immunoreactive neurons were
      significantly larger in males and females from the Amargosa River population than
      in same sex pupfish from Big Spring. Our findings suggest that the divergent
      ecological conditions of these two habitats have brought about changes in AVT
      pathways in the brain.

PMID- 14723883
TI  - Jun localization in cytosolic and nuclear compartments in brain-pituitary system
      of the frog, Rana esculenta: an analysis carried out in parallel with GnRH
      molecular forms during the annual reproductive cycle.
AB  - The presence of c-jun like mRNA was assessed in the brain of the frog, Rana
      esculenta, during the annual sexual cycle. In parallel, Jun protein and GnRH
      molecular form (mammalian and chicken II also indicated as GnRH1 and GnRH2,
      respectively) activity was studied in order to establish possible relationships.
      Northern blot analysis of total RNA reveals the presence of a 2.7 kb c-jun-like
      mRNA. Western blots, carried out on cytoplasmic and nuclear protein extracts,
      show the presence of Jun immunoreactive band of 39 kDa in brain and pituitary.
      Fluctuations of c-jun-like mRNA and Jun immunoreactive protein (cytoplasmic and
      nuclear) levels in brains during the year indicate relationships among
      transcription, translation, and nuclear activity. In particular, mRNA levels
      increase gradually from September until November when Jun protein concentration
      peaks in cytosolic extracts. Conversely, the nuclear protein reaches highest
      concentration in July when the cytosolic level shows low values.
      Immunocytochemical studies confirm the presence of Jun immunoreactivity in both
      cytoplasmic and nuclear compartments of several brain areas, including those
      primarily involved in gonadotropin discharge (e.g., anterior preoptic area and
      preoptic nucleus). GnRH molecular forms and Jun are colocalized in anterior
      preoptic area and preoptic nucleus. Moreover, during the period characterized by
      GnRH release, Jun levels strongly decrease in nuclei. Finally, we show that
      treatments with a GnRH analog (buserelin, Hoechst, Frankfurt) increase Jun levels
      in brain nuclear extracts.

PMID- 14723884
TI  - The effects of recombinant bovine somatotropin (rbST) on tissue IGF-I, IGF-I
      receptor, and GH mRNA levels in rainbow trout, Oncorhynchus mykiss.
AB  - Numerous studies demonstrated that rbST increased growth rates in several fish
      species, and several species exhibit GH production in tissues other than the
      pituitary. The role of tissue GH and IGF-I in regulating fish growth is poorly
      understood. Therefore an experiment was conducted to examine the effects of rbST
      treatment on tissue GH, IGF-I, and IGF-I receptor-A (rA) expression in rainbow
      trout. Rainbow trout (550 +/- 10 g) received either intra-peritoneal injections
      of rbST (120 microg/g body weight) or vehicle on days 0 and 21, and tissue
      samples were collected on days 0, 0.5, 1, 3, 7, and 28 (n = 6/day/trt). Total RNA
      was isolated and assayed for steady-state levels of IGF-I, IGF-IrA, and GH mRNA
      using quantitative RT-PCR. Insulin-like growth factor-I mRNA levels increased in
      liver, gill, gonad, muscle, brain, and intestine in response to rbST treatment (P
      < 0.10). Liver IGF-I mRNA increased (P < 0.01) 0.5 day after treatment and
      remained elevated throughout the trial. Intestine IGF-I mRNA increased (P < 0.05)
      in treated fish from day 1 to day 3, then decreased to day 7 and increased again
      at day 28, and remained elevated above control levels throughout the trial. Gill
      IGF-I mRNA levels increased (P < 0.05) 1 day after treatment and remained
      elevated throughout the trial. Heart IGF-IrA mRNA levels decreased (P < 0.05)
      while gonad GH mRNA levels increased (P < 0.10) following rbST treatment. These
      results demonstrate that rbST treatment increased IGF-I mRNA levels in extra
      hepatic tissues, and decreased heart IGF-IrA and increased gonad GH mRNA levels.
      Because the primary source for endocrine IGF-I is liver, the increased IGF-I mRNA
      reported in extra-hepatic tissues may indicate local paracrine/autocrine actions
      for IGF-I for local physiological functions.

PMID- 14723885
TI  - Response of the somatotropic axis of juvenile coho salmon to alterations in plane
      of nutrition with an analysis of the relationships among growth rate and
      circulating IGF-I and 41 kDa IGFBP.
AB  - The effect of different feeding levels on plasma levels of insulin-like growth
      factor-I (IGF-I), 41 kDa insulin-like growth factor binding protein (41 kDa
      IGFBP), and growth hormone (GH) were assessed in post-smolt coho salmon. Fish
      were fed at either stable (1 and 2% body weight/day) or varying (1-0.5-1%, 2-0.5
      2% body weight/day) feeding rates and plasma was sampled from 10 fish/treatment
      at 2-3 week intervals over five dates from June to September, resulting in a
      total of 200 samples. Fish fed at higher rates grew faster and had higher plasma
      IGF-I and 41 kDa IGFBP levels. Plasma GH levels were variable but generally
      showed an inverse relationship to feeding rate. Both plasma IGF-I and 41 kDa
      IGFBP increased seasonally, average IGF-I levels doubled from June to September,
      regardless of feeding rate. On any one date both IGF-I and 41 kDa IGFBP were
      highly related to growth rate with regression coefficients ranging from 0.36 to
      0.68 (IGF-I) and from 0.33 to 0.70 (41 kDa IGFBP). No relationship was found
      between IGF-I:41 kDa IGFBP ratio and individual growth rate. Overall, both
      feeding rate and date were important in explaining variation in IGF-I and 41 kDa
      IGFBP levels.

PMID- 14723886
TI  - Molecular cloning and developmental expression patterns of thyroid hormone
      receptors and T3 target genes in the turbot (Scophtalmus maximus) during post
      embryonic development.
AB  - Thyroid hormones (TH) are pleiotropic factors important for many developmental
      and physiological functions in vertebrates and particularly in amphibian
      metamorphosis. Their effects are mediated by two specific receptors (TRalpha and
      TRbeta), which are ligand-dependent transcription factors, members of the nuclear
      hormone receptor superfamily. Besides their pivotal role in amphibian
      metamorphosis, TH are also critical for fish metamorphosis. As this later role of
      TH is less studied, we analyzed their action in the turbot (Scophtalmus maximus),
      a metamorphosing flat fish. We describe the isolation of sequences for the turbot
      orthologs of a number of Xenopus genes, which are induced during amphibian
      metamorphosis. Developmental expression of these genes during turbot
      metamorphosis was studied by several methods and the expression patterns of these
      genes compared with those in Xenopus and flounder. We find that the period
      between the onset and the end of eye migration (day 22 to day 30 post-hatching)
      most likely corresponds to the metamorphic climax with either high TRalpha or
      high TH levels. Our results show that in contrast to amphibians, it is TRalpha
      and not TRbeta mRNA that is up-regulated during metamorphosis. Our results
      highlight the notion that TH regulates, through a rise of TR expression, a
      genetic cascade during turbot metamorphosis. The fact that TH regulates
      metamorphosis in amphibian and teleost fishes suggests that TH-regulated
      metamorphosis is a post-embryonic process conserved in most vertebrates.

PMID- 14723887
TI  - Regulation of ecdysteroid secretion from the Y-organ by molt-inhibiting hormone
      in the American crayfish, Procambarus clarkii.
AB  - In crustaceans, molt-inhibiting hormone (MIH) has been proposed to regulate
      molting by inhibiting the secretion of ecdysteroids from the Y-organ. Thus, MIH
      titer in the hemolymph should be inversely related to ecdysteroid titers during
      the molt cycle. However, it has not been demonstrated whether the MIH titer in
      the hemolymph changes during the molt cycle. The purpose of this study was to
      determine the changes in the MIH titers in the hemolymph during the molt cycle of
      the American crayfish, Procambarus clarkii, and to discuss the role of MIH in
      regulation of molting. As predicted by the hypothesis, the hemolymph MIH titer
      was high at the intermolt stage when the hemolymph ecdysteroid titer was low, and
      the MIH titer decreased to a basal level at the early premolt stage when the
      hemolymph ecdysteroid titer began to increase slightly. At the middle premolt
      stage when the hemolymph ecdysteroid titer increased, the MIH titer was restored
      to a level as high as that during the intermolt stage. This is in contradiction
      to the hypothesis. However, the Y-organs at this stage scarcely responded to MIH
      both in vitro and in vivo. The present findings suggest that ecdysteroid
      secretion from the Y-organ may be regulated not only by changes in the hemolymph
      MIH titer, but also by changes in the responsiveness of the Y-organ to MIH.

PMID- 14723888
TI  - Maternal corticosterone is transferred to avian yolk and may alter offspring
      growth and adult phenotype.
AB  - Many environmental perturbations may elevate plasma corticosterone in laying
      birds, including disease, poor body condition, high predator density,
      anthropogenic disturbance, and/or food scarcity. When adverse conditions are not
      dire enough to dictate foregoing reproduction, maternal corticosterone in egg
      yolk may phenotypically engineer offspring so as to maximize success under the
      constraints of the local environment. We tested the hypotheses that
      corticosterone in avian egg yolk should correlate with corticosterone in maternal
      circulation at the time of laying, and that high corticosterone in yolk should
      then influence offspring development and adult phenotype. We implanted female
      Japanese quail (Coturnix coturnix japonica) with corticosterone-filled or empty
      implants and measured concentrations of corticosterone in the yolk of their eggs.
      Then we incubated the eggs and raised the chicks to test for effects on growth
      and hypothalamo-pituitary-adrenal response to capture and restraint in adult
      offspring. We found that corticosterone implants significantly increased
      corticosterone in yolk. Furthermore, chicks of corticosterone-implanted mothers
      grew more slowly than controls and showed higher activity of the hypothalamo
      adrenal axis in response to capture and restraint as adults. These results
      suggest that stress experienced by a laying bird has significant effects on
      offspring development and adult phenotype, possibly mediated by the transfer of
      maternal corticosterone to yolk.

PMID- 14723889
TI  - Gonadotropin-induced testosterone response in peripubertal male alligators.
AB  - Based on the response to three different gonadotropin challenges, we evaluated
      seasonal production of testosterone in a group of captive-raised four-year-old
      male alligators that varied in size. To stimulate gonadal steroidogenesis, we
      injected each alligator with ovine FSH (150 ng/ml plasma). Plasma testosterone
      concentrations were measured in repeated blood samples taken between 0 and 72 h
      after FSH injection. To determine if there was seasonal variation in response, we
      repeated the experiment on the same alligators three times during the breeding
      season (March, May, and July, 2000). All alligators responded to exogenous FSH by
      exhibiting increased plasma concentrations of testosterone (p < 0.0001 for all
      months). However, the degree of the response depended on body size. Thus, larger
      alligators produced more testosterone and were more affected by changes in season
      compared to smaller alligators. We have previously observed that juvenile male
      alligators display seasonal changes in plasma testosterone concentrations that
      mimic the cycle observed in adult males. Our present data suggest that seasonal
      changes in plasma testosterone appear to be associated not only with changes in
      gonadotropin release but in gonadal responsiveness as well. We propose, given
      these observations, that alligators experience an extended period of puberty,
      during which the gonads synthesize gradually increasing steroid hormone
      concentrations. These peripubertal animals are not juveniles but sub-adults
      capable of responding to the seasonal signals associated with reproductive timing
      in adults.

PMID- 14723890
TI  - Maintenance of Atlantic salmon (Salmo salar) at elevated temperature inhibits
      cytochrome P450 aromatase activity in isolated ovarian follicles.
AB  - Atlantic salmon (Salmo salar) broodstock were transferred from natural (12-16
      degrees C) to controlled temperatures of 14, 18 or 22 degrees C for 3 months
      during vitellogenesis. Fertility and survival were significantly reduced in eggs
      from broodstock held at 22 degrees C relative to 14 or 18 degrees C. Endocrine
      mechanisms were disrupted after only one month at 22 degrees C, as evidenced by
      decreased plasma vitellogenin (Vtg) and increased plasma testosterone (T) levels
      and, at later stages, decreased levels of plasma 17beta-estradiol (E2). In vitro
      incubations of isolated ovarian follicles were carried out at monthly intervals,
      with follicles exposed to human chorionic gonadotropin, N-2-0-dibutyryladenosine
      3,5-cyclic monophosphate, and the gonadal steroid precursors 17
      hydroxyprogesterone, androstenedione, and T. After one month of exposure to
      controlled temperature, T synthesis was generally enhanced in response to all
      treatments at all temperatures, but E2 synthesis was inhibited at 22 degrees C,
      suggesting temperature impairment of cytochrome P450 aromatase (P450arom)
      synthesis or activity. The effect became less marked as follicles matured
      suggesting that temperature sensitivity is stage dependent. The results of this
      study suggest that the inhibitory effects of elevated temperature on E2 and Vtg
      synthesis, and subsequent egg development found in the present and earlier
      studies, arise at least partly, from temperature modulation of P450arom.

PMID- 14723891
TI  - Identification of GYRKPPFNGSIFamide (crustacean-SIFamide) in the crayfish
      Procambarus clarkii by topological mass spectrometry analysis.
AB  - A new concept relating to the purification protocol for biological proteins and
      peptides has been designed as "topological mass spectrometry analysis," in
      combination with MALDI-TOF MS using slices of tissues, chromatographic
      purification from the extract of tissues, molecular cloning for the determination
      of the precursor structure, and capillary LC-MS/MS analysis for elucidation of
      its posttranslational modifications. In an actual application, we identified an
      alpha-amidated neuropeptide from the red swamp crayfish (Procambarus clarkii)
      brain. Initially, an MS number of around m/z 1382 was found by the direct MALDI
      TOF MS analysis with slices of the accessory lobe of the brain. After two steps
      of reversed-phase HPLC separation with brain extract, the structure of a 1381 Da
      peptide was sequenced to the GYRKPPFNGSIFamide (named crustacean-SIFamide).
      Subsequently, the cDNA has been characterized and encodes a 76 amino acid
      precursor protein that contains a signal sequence, one copy of GYRKPPFNGSIFG and
      one additional peptide. The RT-PCR analysis implied that the mRNA of the
      neuropeptide was expressed throughout the nervous system of the crayfish.
      Furthermore, immunostaining demonstrated that the neuropeptide is distributed in
      the olfactory lobe, accessory lobe, olfactory globular tract, and olfactory lobe
      cells. In addition, database searches revealed that there are homologous
      sequences of the AYRKPPFNGSIFamide in the genome library of fruitfly Drosophila
      melanogaster and AYRKPPFNGSLFamide isolated from the grey fleshfly Neobellieria
      bullata, and GYRKPPFNGSIFamide isolated from the giant tiger prawn Penaeus
      monodon. These results suggested that the neuropeptide family might be widely
      distributed in arthropods and plays a significant role in the nervous system.

PMID- 14723892
TI  - A quantitative real-time RT-PCR assay for salmon IGF-I mRNA, and its application
      in the study of GH regulation of IGF-I gene expression in primary culture of
      salmon hepatocytes.
AB  - The hormone insulin-like growth factor-I (IGF-I) regulates vertebrate growth. The
      liver produces most circulating IGF-I, under the control of pituitary growth
      hormone (GH) and nutritional status. To study the regulation of liver IGF-I
      production in salmon, we established a primary hepatocyte culture system and
      developed a TaqMan quantitative real-time RT-PCR assay for salmon IGF-I gene
      expression. A portion of the coho salmon acidic ribosomal phosphoprotein P0 (ARP)
      cDNA was sequenced for use as a reference gene. A systematic bias across the 96
      well PCR plate was discovered in an initial IGF-I assay, which was corrected when
      the assay was redesigned. IGF-I mRNA levels measured with the validated assay
      correlated well with levels measured with an RNase protection assay, and were
      highest in liver compared with other tissues. We examined the time course of
      hepatocyte IGF-I gene expression over 48 h in culture, the response to a range of
      GH concentrations in hepatocytes from fed and fasted fish, and potential effects
      of variation in IGF-I in the medium. IGF-I gene expression decreased over time in
      culture in hepatocytes in plain medium, and in cells treated with 5 nM GH with or
      without a combination of metabolic hormones (1 microM insulin, 100 nM
      triiodothyronine, and 0.1 nM dexamethasone). GH stimulated IGF-I gene expression
      at all time points. In cells treated with GH plus metabolic hormones, IGF-I gene
      expression was intermediate between the controls and GH alone. Increasing
      concentrations of GH resulted in biphasic IGF-I gene expression response curves
      in cells from fed and fasted fish, with the threshold for stimulation from 0.5 to
      2.5 nM GH, maximal response from 5 to 50 nM, and a reduced response at 500 nM.
      Medium IGF-I (5 nM) did not affect basal or GH stimulated IGF-I gene expression.
      This study shows that primary hepatocyte culture and the TaqMan IGF-I assay can
      be used to study the regulation of hepatic IGF-I gene expression in salmon, and
      provides the first evidence of a biphasic response to GH concentration in fish
      hepatocyte culture.

PMID- 14723893
TI  - Adaptation of ticks to a blood-feeding environment: evolution from a functional
      perspective.
AB  - Ticks had to adapt to an existing and complex vertebrate hemostatic system from
      being free-living scavengers. A large array of anti-hemostatic mechanisms evolved
      during this process and includes blood coagulation as well as platelet
      aggregation inhibitors. Several questions regarding tick evolution exist. What
      was the nature of the ancestral tick? When did ticks evolve blood-feeding
      capabilities? How did these capabilities evolve? Did host specificity influence
      the adaptation of ticks to a blood-feeding environment? What are the implications
      of tick evolution for future research into tick biology and vaccine development?
      We investigate these questions in the light of recent research into protein
      superfamilies from tick saliva. Our conclusions are that the main tick families
      adapted independently to a blood-feeding environment. This is supported by major
      differences observed in all processes involved with blood-feeding for hard and
      soft ticks. Gene duplication events played a major role in the evolution of novel
      protein functions involved in tick-host interactions. This occurred during the
      late Cretaceous and was stimulated by the radiation of birds and placental
      mammals, which provided numerous new niches for ticks to adapt to a new
      lifestyle. Independent adaptation of the main tick families to a blood-feeding
      environment has several implications for future tick research in terms of tick
      genome projects and vaccine development.

PMID- 14723894
TI  - A new model for proton pumping in animal cells: the role of pyrophosphate.
AB  - The H+-PPase activity was characterized in membrane fractions of ovary and eggs
      of Rhodnius prolixus. This activity is totally dependent on Mg2+, independent of
      K+ and strongly inhibited by NaF, IDP and Ca2+. The membrane proteins of eggs
      were analyzed by western blot using antibodies to the H+-PPase from Arabidopsis
      thaliana. The immunostain was associated with a single 65-kDa polypeptide. This
      polypeptide was immunolocalized in yolk granule membranes by optical and
      transmission electron microscopy. We describe the acidification of yolk granules
      in the presence of PPi and ATP. This acidification is inhibited in the presence
      of NAF, Ca2+ and antibodies against H+-PPase. These data show for the first time
      in animal cells that acidification of yolk granules involves an H+-PPase as well
      as H+-ATPase.

PMID- 14723895
TI  - Characterization of cDNAs encoding putative laccase-like multicopper oxidases and
      developmental expression in the tobacco hornworm, Manduca sexta, and the malaria
      mosquito, Anopheles gambiae.
AB  - Laccase (EC 1.10.3.2) is an enzyme with p-diphenol oxidase activity that is a
      member of a group of proteins collectively known as multicopper, or blue copper,
      oxidases. Laccase is hypothesized to play an important role in insect cuticle
      sclerotization by oxidizing catechols in the cuticle to their corresponding
      quinones, which then catalyze protein cross-linking reactions. To facilitate
      studies of the structure, function and regulation of insect laccases, we have
      cloned two cDNAs for laccases from the tobacco hornworm, Manduca sexta (MsLac1
      and 2), and one from the malaria mosquito, Anopheles gambiae (AgLac1). The MsLac1
      and 2 cDNAs encode proteins of 801 amino acids (aa) and 760 aa, respectively,
      while the AgLac1 cDNA encodes a protein of 1009 aa. All three cDNAs contain
      putative secretion signal sequences, and the 10 histidines and one cysteine that
      form the copper-binding centers, as well as a methionine in the T1 copper center.
      Novel to the insect laccases, relative to both fungal and plant laccases, is a
      longer amino-terminal sequence characterized by a unique domain consisting of
      several conserved cysteine, aromatic, and charged residues. Northern blot
      analyses identified single transcripts of approximately 3.6, 3.5, and 4.4 kb for
      MsLac1, MsLac2, and AgLac1, respectively, and also showed that AgLac1 was
      expressed in all life stages of the mosquito. RT-PCR revealed that the MsLac1
      transcript was most abundant in the midgut, Malpighian tubules, and epidermis,
      whereas the MsLac2 transcript was most abundant in the epidermis. MsLac2 showed
      strong expression in the pharate pupal and reduced expression in the early pupal
      epidermis, consistent with the laccases' presumed role in cuticle sclerotization.

PMID- 14723896
TI  - Identification of 1-lysophosphatidylethanolamine (C(16:1)) as an antimicrobial
      compound in the housefly, Musca domestica.
AB  - We observed that a methanolic whole body extract of uninfected last instar larvae
      of the housefly, Musca domestica, displayed antifungal and antibacterial
      activity. We have further purified this extract to a single active fraction using
      reversed phase high performance liquid chromatography. The pure fraction
      inhibited growth of the Gram-positive bacteria Bacillus thuringiensis and the
      yeast Saccharomyces cerevisiae, but not the Gram-negative bacteria Escherichia
      coli. The active compound was determined to have a molecular mass of 451.2 Da.
      Further analysis by nuclear magnetic resonance identified the substance as mono
      unsaturated 1-lysophosphatidylethanolamine (C(16:1)) (1-LPE). The structurally
      different and more common 2-LPE have been described as mediators of the
      antimicrobial activity of rimenophenazine antibiotic agents (Van Rensburg et al.,
      1992). Our results suggest that the isolated 1-LPE displays a higher activity in
      comparison, possibly based on structure-specific differences in activity.

PMID- 14723897
TI  - Women, work and musculoskeletal health.
AB  - Why are employed women at increased risk for upper limb musculoskeletal disorders
      and what can this tell us about the way work and family life shape health?
      Despite increases in women's labour force participation, gender differences in
      work-related health conditions have received little research attention. This
      appears be the first study to examine why employed women are much more likely
      than men to experience upper body musculoskeletal disorders. A mailed self-report
      survey gathered data from 737 Australian Public Service employees (73% women).
      The majority of respondents were clerical workers (73%). Eighty one per cent
      reported some upper body symptoms; of these, 20% reported severe and continuous
      upper body pain. Upper body musculoskeletal symptoms were more prevalent and more
      severe among women. The gender difference in symptom severity was explained by
      risk factors at work (repetitive work, poor ergonomic equipment), and at home
      (having less opportunity to relax and exercise outside of work). Parenthood
      exacerbated this gender difference, with mothers reporting the least time to
      relax or exercise. There was no suggestion that women were more vulnerable than
      men to pain, nor was there evidence of systematic confounding between perceptions
      of work conditions and reported health status. Changes in the nature of work mean
      that more and more employees, especially women, use computers for significant
      parts of their workday. The sex-segregation of women into sedentary, repetitive
      and routine work, and the persisting gender imbalance in domestic work are
      interlinking factors that explain gender differences in musculoskeletal
      disorders.

PMID- 14723898
TI  - Women, work, and well-being 1950-2000: a review and methodological critique.
AB  - In this research synthesis, we summarize 161 measures of the effects of women's
      employment on well being reported between 1950 and 2000. Variations in the
      conceptualization and measurement of employment and health outcomes and the
      difficulty in distinguishing social selection from social causation limit the
      inferences that can be drawn from the evidence. Therefore, we distinguish two
      types of studies. Longitudinal studies measuring relevant covariates at the first
      measurement occasion and statistically controlling them in multivariate analyses
      providing effect-size information are classified as Type II studies. The
      remaining studies are classified as Type I studies. The main findings were that
      (1) results from methodologically sound Type II studies confirm the cross
      sectional finding that paid employment has no adverse effects on women; (2) the
      outcome groups psychological distress, subjective health, cardiovascular risks
      and disease, and mortality do not converge completely.

PMID- 14723899
TI  - Factors associated with the use of publicly funded services by Hong Kong Chinese
      older adults.
AB  - This article analyzes cross-sectional data collected from a representative
      community sample of 2003 Chinese elderly people aged 60 or above in Hong Kong. We
      examined whether the use of publicly funded health services by older adults is
      equitable under the framework of Andersen model. A number of predisposing,
      enabling, and need factors were assessed as predictors of utilization in four
      categories of services including hospital admission, emergency room, general
      outpatient clinics, and specialist outpatient clinics. It was found that
      utilization of these four health services was consistently correlated with need
      factors. Specifically, self-rated health status and particular types of chronic
      illness were consistently and significantly related to utilization for all four
      of services in Hong Kong. On the other hand, age and family support were related
      to hospital admission whereas functional impairment was associated with the use
      of emergency room and general outpatient clinics. Findings suggest that publicly
      funded health services in Hong Kong are used equitably by elderly people.

PMID- 14723900
TI  - Recessions lower (some) mortality rates: evidence from Germany.
AB  - In his article with the provocative title "Are Recessions Good for Your Health?",
      Ruhm (J. Health Econ. 21(4) (2000) 659) has found robust and consistent evidence
      that the total mortality rate, age-specific mortality rates as well as most
      specific mortality causes are pro-cyclical. His finding that high unemployment
      rates are associated with lower mortality and vice versa stands in stark contrast
      to Brenner's earlier work, who found the opposite effect, possibly after a time
      lag. Ruhm controls for state-specific effects in a panel of US states over the
      period 1972-1991, whereas Brenner's work is based on time-series analysis.
      Extending and improving upon Ruhm's original analysis, we analyse the effect of
      state unemployment and economic growth rates on mortality in the states of
      Germany over the period 1980-2000, both in a static and a dynamic econometric
      model. Controlling for state-specific effects, we find evidence that aggregate
      mortality rates for all age groups taken together as well as most specific age
      groups are lower in recessions. The same is true for mortality from
      cardiovascular diseases, pneumonia and influenza, motor vehicle accidents and
      suicides, but not for necessarily for other specific mortality causes. In
      particular, there is never a statistically significant effect on homicides, other
      external effects and malignant neoplasms. There are also few differences apparent
      between the effect on male and female mortality. If we do not control for state
      specific effects, then we often arrive at the opposite result with higher
      unemployment being associated with higher mortality. This suggests that a failure
      to control for time-invariant state-specific effects leads to omitted variable
      bias, which would erroneously suggest that mortality rates move counter
      cyclically. Overall, we can confirm Ruhm's main finding for another country:
      recessions lower some, but not all, mortality rates in the case of Germany.

PMID- 14723901
TI  - Association of stereotypes about physicians to health care satisfaction, help
      seeking behavior, and adherence to treatment.
AB  - The present research consists of three studies examining the role of patients'
      stereotypes about health care providers in the health care decision process.
      Study 1 examined the association of stereotypes to health care satisfaction and
      help-seeking behavior among a low-income clinic sample; Study 2 examined the
      relationship of stereotypes to satisfaction and adherence to treatment among low
      income individuals living with HIV; and Study 3 examined the association of
      stereotypes to satisfaction and help-seeking among a sample of homeless
      individuals. Overall findings indicate that individuals who held more negative
      stereotypes about physicians sought care less often when sick, were less
      satisfied with the care that they did obtain, and were less likely to adhere to
      physician recommendations for treatment. Moreover, African Americans, but not
      Whites, with more positive stereotypes reported better adherence in Study 2 and
      were more satisfied with their health care in Study 3. Our findings point to the
      need to better understand the role of patients' beliefs about health care in
      predicting health care satisfaction and health behaviors.

PMID- 14723902
TI  - A question of place: medical power in rural Australia.
AB  - In Australia, like many countries, government, medicine and the community have
      maintained an interdependent and symbiotic relationship based on mutual resource
      dependency and reciprocity. The services of medicine have been indispensable to
      government and the community and in return medicine has achieved power, elitism
      and financial gain. Traditionally, doctors have controlled and directed medical
      knowledge in an absolute manner and this has been the basis of increasing power
      and dominance. There are, however, claims that medicine's power and dominance
      over the health care system is being eroded by the emergence of major social
      trends. The corporatization of medicine, manageralism and proletarianization are
      touted as factors that are increasingly countervailing medical dominance and
      power. Whilst it could be suggested that as these trends become more firmly
      established government and the community gain greater discretionary control over
      how the resources of medicine can be allocated and utilized, this article argues
      that the geographic and social dimensions of the community in which doctors
      practice must be considered. Using a qualitative descriptive approach research
      was conducted in rural Victoria, Australia. The overall aim of the study was to
      identify the issues that impact upon service delivery in rural hospitals. The
      most significant issue that emerged related to medical relationships. The results
      of this research indicate that in this rural area the power of medicine is
      strengthened and institutionalized by geographically determined resource control.
      The sustainability of rural communities is linked to the ability of the town to
      attract and retain the services of a doctor. Crucial shortages of rural doctors
      provide medicine with a mandate to dictate the way in which medical resources
      will be allocated and used by hospitals and the community. Organizations that
      control critical resources are in an extremely powerful position to control
      others. Doctors in rural Victoria maintain a position of strength and use their
      power to exert control over the state, the community and the hospital. Although
      medical power and dominance may be declining in some areas, in rural Victoria it
      remains firmly entrenched.

PMID- 14723903
TI  - Living with conflicts-ethical dilemmas and moral distress in the health care
      system.
AB  - During the last decade, the Swedish health care system has undergone fundamental
      changes. The changes have made health care more complex and ethics has
      increasingly become a required component of clinical practice. Considering this,
      it is not surprising that many health care professionals suffer from stress
      related disorders. Stress due to ethical dilemmas is usually referred to as
      "moral distress". The present article derives from Andrew Jameton's development
      of the concept of moral distress and presents the results of a study that, using
      focus group method, identifies situations of ethical dilemmas and moral distress
      among health care providers of different categories. The study includes both
      hospital clinics and pharmacies. The results show that all categories of staff
      interviewed express experiences of moral distress; prior research has mostly
      focused on moral distress experienced by nurses. Second, it was made clear that
      moral distress does not occur only as a consequence of institutional constraints
      preventing the health care giver from acting on his/her moral considerations,
      which is the traditional definition of moral distress. There are situations when
      the staff members do follow their moral decisions, but in doing so they clash
      with, e.g. legal regulations. In these cases too, moral distress occurs. Hitherto
      research on moral distress has focused on the individual health care provider and
      her subjective moral convictions. Our results show that the study of moral
      distress must focus more on the context of the ethical dilemmas. Finally, the
      conclusion of the study is that the work organization must provide better support
      resources and structures to decrease moral distress. The results point to the
      need for further education in ethics and a forum for discussing ethically
      troubling situations experienced in the daily care practice for both hospital and
      pharmacy staff.

PMID- 14723904
TI  - Prevention and genetic testing for breast cancer: variations in medical
      decisions.
AB  - The discovery linking the genes BRCA1&2 to familial breast cancer played an
      important role in the clinical practice of geneticists and physicians. The
      availability of genetic tests for BRCA gene mutations prompted cancer geneticists
      to give information about genetic risk and to assess many women with a personal
      or family history of breast or ovarian cancer to inform them of preventive
      measures. These consist mainly of breast self-examination, mammography screening,
      chemoprevention and prophylactic surgery (mastectomy, oophorectomy). This paper
      examines clinical practices related to hereditary breast cancer testing and
      introduces a number of results from a survey carried out, between 1996 and 1998,
      in three clinics located in Montreal (Quebec, Canada), Marseilles (France) and
      Manchester (Great Britain). Results show substantial differences in the way
      cancer geneticists deal with environmental risk factors, breast and ovarian
      cancer testing, and chemoprevention and prophylactic surgery. Differences across
      cities persist in the multivariate analysis, suggesting that attitudes towards
      preventive measures may be partially explained by cultural factors. Different
      dimensions of culture are discussed including the social representation of health
      and risk, the interpretation of scientific evidence and the role of innovation
      leadership.

PMID- 14723905
TI  - The 'hows', 'whos', and 'whens' of screening: gynaecologists' perspectives on
      cervical cancer screening in urban Sweden.
AB  - Population-based screening has contributed to decreased mortality in cervical
      cancer. However, the 'hows', 'whos' and 'whens' of screening still concern health
      professionals and policy makers. As part of a research project aimed at examining
      a population-based cervical cancer screening program (PCCSP) from different
      stakeholders' perspectives, the aim of this qualitative interview study was to
      elucidate the views of gynaecologists, working in both public and private
      settings, as stakeholders in the PCCSP in the county of Stockholm, Sweden.
      Results from semi structured interviews with 17 physicians indicate ambiguity in
      their descriptions of the purpose of both the PCCSP and smear testing in general,
      leading to different views about appropriate time intervals for Pap-smear
      testing. The gynaecologists also described experiencing a number of dilemmas
      related to information content and provision-both prior to screening and in
      relation to test results. In addition, the gynaecologists tended to differentiate
      morally through choice of language between women who participate in some form of
      screening and non-attendees of the PCCSP. There also appeared to be distinctions
      in how these gynaecologists conceptualised and discussed women receiving Pap
      smears, dependent on whether they were regarded as within the category of 'my
      patients' (seen by the gynaecologist in a private or public setting) or 'the
      population' (women unknown to the gynaecologist). This study indicates the
      importance of comprehensively analysing the context of professionals' work when
      attempting to understand professional attitudes. Seeming disparities in attitudes
      as well as varying practices may be explained by the simultaneous existence of
      multiple value systems, applied to different patient populations, as found in
      this study.

PMID- 14723906
TI  - Prospects of safe motherhood in Botswana: midwifery training and nurses' ability
      to complete the Botswana obstetric record.
AB  - This paper examines several key factors that determine nurses' ability to
      complete the Botswana Obstetric Record (BOR), an instrument that should help with
      early diagnosis of problems during pregnancy, labour, delivery and the
      puerperium. Using a national sample of 309 nurses working in hospitals, clinics
      and health posts under the local government authority in Botswana, the study
      found that a nurse's ability to complete the BOR was significantly related to
      midwifery training, level of basic nursing training, age group, level of income,
      job satisfaction, adequacy of equipment, attendance of refresher courses, overall
      level of in-service training, reliance on workshops and seminars, peer reliance
      and self-reliance for information on new nursing practices. Multivariate analyses
      indicated that the most competent nurse in completing the BOR was one trained as
      a midwife, working in an adequately equipped health facility, and who often
      consulted with peers as well as attended workshops and seminars. The study
      concludes that it is more important to train all nurses to become midwives than
      to upgrade enrolled nurses to become registered nurses if the plan for safe
      motherhood is to be advanced. Further research is needed to establish the
      objective competence of nurses who claim to be comfortable completing the BOR.

PMID- 14723907
TI  - Effects of illness and disability on job separation.
AB  - Effects of illness and disability on job separation result from both voluntary
      and involuntary processes. Voluntary processes range from the reasoned actions of
      workers who weigh illness and disability in their decision-making, to reactive
      stress-avoidance responses. Involuntary processes include employer discrimination
      against ill or disabled workers. Analyses of the effects of illness and
      disability that differentiate reasons for job separation can illuminate the
      processes involved. This paper reports on an evaluation of effects of illness and
      disability on job separation predicted by theories of reasoned action, stress,
      and employer discrimination against ill and disabled workers. Effects of four
      illness/disability conditions on the rate of job separation for 12 reasons are
      estimated using data from a longitudinal study of a representative sample of the
      Canadian population-the Survey of Labour and Income Dynamics (SLID). Two of the
      four effects that are statistically significant (under conservative Bayesian
      criteria for statistical significance) are consistent with the idea that workers
      weigh illness and disability as costs, and calculate the costs and benefits of
      continuing to work with an illness or disability: (1) disabling illness increases
      the hazard of leaving a job in order to engage in caregiving, and (2) work
      related disability increases the hazard of leaving a job due to poor pay. The
      other two significant effects indicate that: (3) disabling illness decreases the
      hazard of layoff, and (4) non-work disability increases the hazard of leaving one
      job to take a different job. This last effect is consistent with a stress
      interruption process. Other effects are statistically significant under
      conventional criteria for statistical significance, and most of these effects are
      also consistent with cost-benefit and stress theories. Some effects of illness
      and disability are sex and age-specific, and reasons for the specificity of these
      effects are discussed.

PMID- 14723908
TI  - Effects of urbanization, economic development, and migration of workers on
      suicide mortality in Japan.
AB  - The relationships between male or female age-adjusted suicide mortality and
      social life factors for all 47 Japanese prefectures in 1980, 1985 and 1990 were
      investigated by stepwise multiple regression analysis after classification of 20
      social life indicators by factor analysis. During this period, Japan experienced
      the second economic crisis (the so-called secondary oil crisis) in 1980-1983 and
      economic prosperity (bubble economy) in 1986-1990. In all the three years, male
      suicide mortality was significantly related inversely to the urbanization and
      economic development factor, the result of which was consistent with the data in
      our previous study for the years 1970 and 1975. Similarly, the male mortality was
      positively related to the factor of migration of workers in the three years. No
      factor significantly related to female mortality for all the three years was
      found. It is suggested that (1) urbanization was a major determinant which
      prevented male suicide mortality during the past 20 years (1970-1990) in Japan;
      (2) migration of workers became an important factor for male suicide mortality
      during these 10 years; and (3) female suicide mortality was less vulnerable to
      social life factors for these 20 years than the male mortality.

PMID- 14723909
TI  - The generational transmission of socioeconomic inequalities in child cognitive
      development and emotional health.
AB  - Socioeconomic inequalities in the health of adults have been largely attributed
      to lifestyle inequalities. The cognitive development (CD) and emotional health
      (EH) of the child provides a basis for many of the health-related behaviours
      which are observed in adulthood. There has been relatively little attention paid
      to the way CD and EH are transmitted in the foetal and childhood periods, even
      though these provide a foundation for subsequent socioeconomic inequalities in
      adult health. The Mater-University of Queensland Study of Pregnancy (MUSP) is a
      large, prospective, pre-birth cohort study which enrolled 8556 pregnant women at
      their first clinic visit over the period 1981-1983. These mothers (and their
      children) have been followed up at intervals until 14 years after the birth. The
      socioeconomic status of the child was measured using maternal age, family income,
      and marital status and the grandfathers' occupational status. Measures of child
      CD and child EH were obtained at 5 and 14 years of age. Child smoking at 14 years
      of age was also determined. Family income was related to all measures of child CD
      and EH and smoking, independently of all other indicators of the socioeconomic
      status of the child. In addition, the grandfathers' occupational status was
      independently related to child CD (at 5 and 14 years of age). Children from
      socioeconomically disadvantaged families (previous generations' socioeconomic
      status as well as current socioeconomic status) begin their lives with a poorer
      platform of health and a reduced capacity to benefit from the economic and social
      advances experienced by the rest of society.

PMID- 14723910
TI  - Effects of socioeconomic indicators on coronary risk factors, self-rated health
      and psychological well-being among urban Japanese civil servants.
AB  - In Japan, the effects of socioeconomic indicators on coronary risk factors and
      subjective well-being in an urban population have not been compared. The subjects
      of this study were 1361 civil servants (968 men and 393 women, aged 35-64 years)
      working in an urban area of Japan. Screening examinations were conducted from
      April 1997 to March 1998, and a questionnaire survey was conducted in February
      1998. The effects of two socioeconomic indicators, education level (junior high
      school, high school and university education) and employment grade (manual, low
      level nonmanual and high-level nonmanual work), on behavioral and biological
      coronary risk factors, self-rated health and affect balance were investigated
      using multivariate logistic regression analyses. Smoking was found to be
      inversely associated with level of education; compared to university graduates,
      the odds ratios for subjects who had only graduated from high school and those
      for subjects who had only graduated from junior high school were 1.96 and 2.07 in
      men and 3.44 and 5.48 in women, respectively. As for alcohol drinking and
      physical inactivity, relationships were inconsistent in terms of direction by the
      two indicators. Among biological risk factors, diabetes was inversely associated
      with education level in men. Self-rated health, however, was inversely associated
      with employment grade both in men and women, and affect balance was inversely
      associated with employment grade in men. In summary, different effects of two
      socioeconomic indicators, education and employment grade, were seen in some
      coronary risk factors and subjective well-being in an urban Japanese population.
      Our findings should contribute to the elucidation of mechanisms of the
      socioeconomic gradients of risk factors and mortality from coronary heart disease
      in Japan.

PMID- 14723911
TI  - Socioeconomic inequality of obesity in the United States: do gender, age, and
      ethnicity matter?
AB  - This study introduces the concentration index (CI) to assess socioeconomic
      inequality in the distribution of obesity among American adults aged 18-60 years
      old. The CI provides a summary measure of socioeconomic inequality, and enabled
      comparisons across gender, age, and ethnicity. Data from the National Health and
      Nutrition Examination Survey III, 1988-1994 (NHANES III) were used. The degree of
      socioeconomic inequality in obesity varied considerably across gender, age, and
      ethnic groups. Among women, we found a stronger, inverse association between
      socioeconomic status (SES) and obesity compared with men, as well as greater
      socioeconomic inequality among middle-aged adults (41-49) compared to other age
      groups. Consistent with previous studies, we found remarkable ethnic differences
      in the relationship between SES and obesity. Although the extant literature
      documented a higher prevalence of obesity among minorities than in whites, our
      results presented a lower socioeconomic inequality in obesity within minority
      groups. Our analyses suggested that gender, age, and ethnicity could be important
      factors on socioeconomic inequality in obesity.

PMID- 14723912
TI  - Inequality of water fluoridation in Southern Brazil--the inverse equity
      hypothesis revisited.
AB  - The purpose of this ecological study was to investigate the association between
      social and economic indicators at the municipal level and the presence of water
      fluoridation and time when water fluoridation was implemented in the 293
      municipalities of Santa Catarina State in Southern Brazil. Several social and
      economic indicators were obtained from official Brazilian agencies as well as
      from UNICEF. Questionnaires were sent to local authorities and to the local
      government water supply Company to obtain information about the presence or not
      of a fluoridated water supply and the year when fluoridation was implemented.
      Differences in social and economic indicators between municipalities with and
      without fluoridated water and between those that have had this service for
      different lengths of time were compared by the Mann-Whitney U test. In addition,
      multiple logistic regression analyses was performed to identify associations
      between social and economic indicators at the municipal level and presence and
      time of implementation of water fluoridation. Results indicated that larger
      populations are associated with municipalities with fluoridated water. Larger
      populations, higher child development indexes and low illiteracy rates are
      associated with a longer time since the implementation of water fluoridation. The
      finding that less developed municipalities delayed the provision of water
      fluoridation corroborates the inverse equity hypothesis.

PMID- 14723913
TI  - Risk of injury after alcohol consumption: a case-crossover study in the emergency
      department.
AB  - This paper reports a case-crossover analysis in a sample of 961 patients who
      consulted the emergency department (ED) due to an injury in Santa Clara,
      California, and in Pachuca, Mexico. In the analysis in which usual alcohol
      consumption during the last 12 months served as the control value, the estimated
      relative risk of injury in the hour after alcohol consumption, as compared with
      no alcohol consumption during that time, was 4.33 (CI, 3.55-5.27). After
      controlling for alcohol use in the 1-h period before injury, the relative risks
      for consecutive 1-h periods (2-6 h) before the injury were not significantly
      greater than one, indicating that the induction time was less than 1 h. The
      relative risk varied greatly depending on race-ethnicity and acculturation among
      the Hispanics in Santa Clara, with Mexicans in Pachuca showing the highest risk
      and the high acculturation group in Santa Clara showing the lowest risk. Violence
      related injuries were associated with higher relative risk. Relative risk also
      varied depending on the presence of alcohol dependence and usual frequency of
      drunkenness: patients with alcohol dependence and patients with high frequency of
      usual drunkenness had lower risks than patients without alcohol dependence and
      with lower self-reported episodes of drunkenness in the last year. When blood
      alcohol content at ED admission was used instead of self-reported alcohol
      consumption, similar results were obtained. These findings have important public
      health consequences. Each episode of alcohol consumption results in an increase
      in the short-term risk for an injury, especially for a violence-related injury.
      Patients with the lowest usual involvement with alcohol are subject to a higher
      elevation in their risk for an injury immediately after alcohol consumption
      compared to patients who drink more heavily.

PMID- 14723914
TI  - "Iceland Inc."?: On the ethics of commercial population genomics.
AB  - A detailed analysis of the Icelandic commercial population-wide genomics database
      project of deCODE Genetics was performed for the purpose of providing ethics
      insights into public/private efforts to develop genetic databases. This analysis
      examines the moral differences between the general case of governmental
      collection of medical data for public health purposes and the centralized
      collection planned in Iceland. Both the process of developing the database and
      its design vary in significant ways from typical government data collection and
      analysis activities. Because of these differences, the database may serve the
      interests of deCODE more than it serves the interests of the public, undermining
      the claim that presumed consent for this data collection and its proprietary use
      is ethical. We believe that there is an evolving consensus that informed consent
      of participants must be secured for population-based genetics databases and
      research. The Iceland model provides an informative counterexample that holds key
      ethics lessons for similar ventures.

PMID- 14723915
TI  - Is informed consent a solution to contractual problems? A comment on the article
      '"Iceland Inc."?: On the Ethics of Commercial Population Genomics' by Jon F.
      Merz, Glenn E. McGee, and Pamela Sankar.

PMID- 14723917
TI  - Assessing the applicability of the 1D flux theory to full-scale secondary
      settling tank design with a 2D hydrodynamic model.
AB  - The applicability of the one-dimensional idealized flux theory (1DFT) for the
      design of secondary settling tanks (SSTs) is evaluated by comparing its predicted
      maximum surface overflow (SOR) and solids loading (SLR) rates with that
      calculated with the two-dimensional computational fluid dynamics model SettlerCAD
      using as a basis 35 full-scale SST stress tests conducted on different SSTs with
      diameters from 30 to 45m and 2.25-4.1m side water depth (SWD), with and without
      Stamford baffles. From the simulations, a relatively consistent pattern appeared,
      i.e. that the 1DFT can be used for design but its predicted maximum SLR needs to
      be reduced by an appropriate flux rating, the magnitude of which depends mainly
      on SST depth and hydraulic loading rate (HLR). Simulations of the Watts et al.
      (Water Res. 30(9)(1996)2112) SST, with doubled SWDs and the Darvill new (4.1m)
      and old (2.5m) SSTs with interchanged depths, were run to confirm the sensitivity
      of the flux rating to depth and HLR. Simulations with and without a Stamford
      baffle were also performed. While the design of the internal features of the SST,
      such as baffling, has a marked influence on the effluent SS concentration while
      the SST is underloaded, these features appeared to have only a small influence on
      the flux rating, i.e. capacity, of the SST. Until more information is obtained,
      it would appear from the simulations that the flux rating of 0.80 of the 1DFT
      maximum SLR recommended by Ekama and Marais (Water Pollut. Control
      85(1)(1986)101) remains a reasonable value to apply in the design of full-scale
      SSTs-for deep SSTs (4m SWD) the flux rating could be increased to 0.85 and for
      shallow SSTs (2.5m SWD) decreased to 0.75. It is recommended that (i) while the
      apparent interrelationship between SST flux rating and depth suggests some
      optimization of the volume of the SST, this be avoided and (ii) the depth of the
      SST be designed independently of the surface area as is usually the practice and
      once selected, the appropriate flux rating applied to the 1DFT estimate of the
      surface area.

PMID- 14723918
TI  - Phosphorus in periphyton mats provides the best metric for detecting low-level P
      enrichment in an oligotrophic wetland.
AB  - Growing concern over the ecological consequence of phosphorus (P) enrichment in
      freshwater wetlands has elicited considerable debate over the concentration of
      water column P associated with eutrophication. In the oligotrophic Everglades,
      the displacement of native communities by enriched ones is widespread and has
      occurred at sites experiencing only minimal elevations in P input. To help define
      regulatory criteria for P inputs to the Everglades, we constructed an experiment
      that mimics P input to the natural system by continuously delivering P at
      concentrations elevated 5, 15 and 30 microgl(-1) above ambient to 100-m long flow
      through channels. We compared patterns of P accumulation in the water,
      periphyton, detritus and soils among the channel treatments and also along a 16
      km transect from an enriched canal that inflows to the interior of the same
      marsh. Water column TP and SRP were unrelated to input TP concentration in both
      the experiment and the marsh transect. However, concentrations of TP in
      periphyton mats were significantly elevated at all levels of experimental
      enrichment and as far as 2 km downstream from water inputs into the marsh.
      Elevated periphyton TP was associated with significant loss of periphyton
      biomass. In oligotrophic wetlands, traditional measures of water column SRP and
      TP will substantially underestimate P loading because biotically incorporated P
      is displaced from the water column to benthic surfaces. Using periphyton TP as a
      metric of P enrichment is uncomplicated and analogous to pelagic TP assessments
      in lakes where most P is sequestered in phytoplankton.

PMID- 14723919
TI  - Freshwater phytoplankton quantification by chlorophyll a: a comparative study of
      in vitro, in vivo and in situ methods.
AB  - Standard ISO method for chlorophyll a quantification (extraction into ethanol,
      spectrophotometrical quantification at 665 and 750 nm), spectrofluorometry
      (reader for 96 wells, excitation 410 nm, emission 670 nm), and a submersible
      fluorescence probe for in situ phytoplankton quantification (excitation 410, 525,
      570, 590, and 610 nm, emission 685 nm) were compared in different freshwater
      environments-reservoirs and rivers. The ISO method is accepted as a standard
      method but requires sample handling and transport to the laboratory.
      Spectrofluorometry is a sensitive method, even for natural phytoplankton
      populations. Nevertheless, it cannot be recommended for the quantification of
      cyanobacterial water blooms because colonial and filamentous species such as
      Microcystis, Anabaena, or Aphanizomenon display unacceptable variability (18
      33%). The submersible probe featured high correlation with a standard ISO method
      (r=0.97, P<0.05). This probe can provide the selective measurement of
      technologically important phytoplankton groups like cyanobacteria, diatoms, green
      algae, and cryptophytes in lake vertical profiles of up to 100 m. The limitation
      of this instrument is the possible reabsorption of the light signal, e.g. in the
      presence of humic substances, or dense algal blooms. The use of submersible
      probes for in situ phytoplankton quantification can be recommended as a sensitive
      tool for water management, especially in the case of drinking water resources.

PMID- 14723920
TI  - Bioaugmentation for nitrification at cold temperatures.
AB  - Bioaugmentation of nitrifying bacteria for short solids retention time (short
      SRT) nitrification is an attractive alternative for wastewater treatment plants
      in cold climates or for those in the process of upgrading to include
      nitrification. One possible source of ammonia for the production of nitrifying
      bacteria is the liquor generated during the dewatering of anaerobically digested
      sludges. The objectives of this study was to determine the impact of sudden
      decrease in temperature on nitrification rates and to determine if nitrification
      could be accomplished in sequencing batch reactors (SBRs) at 10 degrees C by
      seeding nitrifying bacteria acclimated to 20 degrees C. In this research, biomass
      produced during warm nitrification of dewatering liquor was seeded into cold SBRs
      at various hydraulic retention times from 43.3 to 96 h. The average decreases in
      nitrification rates were 58%, 71% and 82% for biomass cooled to 10 degrees C when
      the biomass was acclimated to 20 degrees C, 25 degrees C and 30 degrees C,
      respectively. The seeded SRTs of the cold SBRs were raised above the minimum
      solids retention time (SRT(min)) required for nitrification. Full ammonia
      nitrogen removal was achieved in cold SBRs that were operated at an apparent SRT
      less than SRT(min).

PMID- 14723921
TI  - A comparison of the carbon balances of a natural lake (L. Ortrasket) and a
      hydroelectric reservoir (L. Skinnmuddselet) in northern Sweden.
AB  - Carbon balances were calculated for the summer stratification period of 2001 for
      the hydroelectric reservoir L. Skinnmuddselet (created in 1989) and the natural
      L. Ortrasket, and estimated on annual basis for both lakes. The reservoir and the
      lake have similar chemical characteristics and are located in adjacent catchments
      in the northern part of Sweden. Our main hypothesis was that the CO(2) production
      and emissions from the reservoir, L. Skinnmuddselet, would be greater than in the
      natural L. Ortrasket, due to the decomposition of flooded vegetation and peat.
      The carbon balances showed that the total production of CO(2) per unit lake
      surface area during the summer was very similar in the natural lake and the
      reservoir (31.3 g Cm(-2) in L. Ortrasket and 25.3 g Cm(-2) in L. Skinnmuddselet).
      The sediments were the major CO(2) source in the reservoir, while most of the
      mineralization in the natural lake occurred in the water column. On annual basis
      the natural L. Ortrasket produced and emitted more CO(2) per unit of lake surface
      area than the reservoir L. Skinnmuddselet since mineralization proceeded during
      winter when L. Skinnmuddselet was emptied for electricity production. Therefore,
      the potential for CO(2) emission was not greater in the reservoir than in the
      natural lake.

PMID- 14723922
TI  - Swine waste treatment by self-heating aerobic thermophilic bioreactors.
AB  - Pig manure represents a very high-strength wastewater that is well suited for a
      self-heating aerobic thermophilic treatment. Here we report the use of 59-L
      Aerobic Thermophilic Sequencing Batch Reactors (AT-SBR) to study the treatment of
      pig manure with a HRT of 6 days. Temperatures up to 75 degrees C were reached
      without external heating by using Venturi-type aerators but these conditions were
      detrimental for the respiratory activity of the microflora. For COD removal,
      better performances were achieved when the temperature was limited to 50 degrees
      C. However, higher temperatures increased the rate of phosphorus crystallisation
      and the volatilisation of ammonia. A temperature of 50 degrees C was enough to
      eliminate faecal coliforms and Campylobacter spp., but 60 degrees C was needed
      for the efficient destruction of Clostridium perfringens. Consequently, an
      operating temperature of 60 degrees C appears to be a good compromise. Under
      these conditions, the BOD(5) decreases from 50.5 to 1.0 g L(-1), yielding a 98%
      removal.

PMID- 14723923
TI  - Reactivity of natural organic matter fractions with chlorine dioxide and ozone.
AB  - The effects of ozone and chlorine dioxide on the aquatic natural organic matter
      (NOM) were studied. The natural as well as oxidised organic matter in aerated and
      sand filtered water were fractionated using XAD, anion-exchange, and cation
      exchange resins procedure into humic acid, hydrophobic acids and neutrals, and
      hydrophilic acids, bases and neutrals. The main NOM components were hydrophobic,
      while oxidation with both ozone and chlorine dioxide increased the proportion of
      hydrophilic fractions. High-pressure size exclusion chromatography with UV-254 nm
      and UV-220 nm detection was used to determine the differences between molecular
      weight distribution of natural and oxidised organic matter fractions. The main
      purpose of this paper was to compare the reactivity of individual NOM fractions
      with oxidants in order to compare the productivity of biodegradable by-products
      after oxidation with chlorine dioxide and ozone. The quantity as well as the
      quality of by-products were analysed by means of ion and gas chromatography.

PMID- 14723924
TI  - Temporal pattern of toxicity in runoff from the Tijuana River Watershed.
AB  - Samples were collected from the Tijuana River under both dry weather (baseflow)
      conditions and during wet weather, and tested for toxicity using Ceriodaphnia
      dubia tests. Toxicity of waters in the Tijuana River was generally low under
      baseflow conditions, but increased markedly during high flow runoff events. In
      order to determine the temporal pattern of toxicity during individual rain
      events, sequential grab samples were collected using an autosampler at 5-7 h
      intervals after the start of the rain event, and tested for acute toxicity. In
      all cases, peak toxicity values (ranging from 2.8 to 5.8TU) for each storm
      occurred within the first 1-2 h of initiation of the rain event, and were
      statistically higher (using the 95% CL) for each of the pre-storm base flow
      values. However, there was no statistically significant correlation (p<0.05)
      between flow rate and toxicity when all storm data was pooled. Additionally, we
      used toxicity identification evaluation (TIE) procedures to attempt to identify
      the classes of chemicals that account for this early storm toxicity. Solid phase
      extraction was the only treatment that showed consistent and significant (P<0.05)
      removal of toxicity. These TIEs, conducted on the most toxic sample of the
      river's flow during runoff events, suggest that non-polar organics may be
      responsible for such toxicity. The temporal pattern of toxicity, both during a
      given storm event and seasonally, indicates that wash-off from the watershed by
      rainfall may deplete the supply of toxicity available for wash-off in subsequent
      events, so that a clearly consistent relationship between flow and toxicity was
      not evident.

PMID- 14723925
TI  - Metal fractionation study on bed sediments of River Yamuna, India.
AB  - The pollution of aquatic ecosystem by heavy metals has assumed serious
      proportions due to their toxicity and accumulative behavior. The toxicity and
      fate of the water borne metal is dependent on its chemical form and therefore
      quantification of the different forms of metal is more meaningful than the
      estimation of its total metal concentrations. In this study fractionation of
      metal ions on bed sediments of River Yamuna has been studied to determine the eco
      toxic potential of metal ions. The investigations suggest that copper have a
      tendency to remain associated with residual, reducible and carbonate fractions.
      The Risk Assessment Code reveal that about 30-50% of lead at most of the sites
      exist in exchangeable fraction while 30-50% of cadmium at almost all the sites is
      either exchangeable or carbonate bound and therefore comes under the high risk
      category and can easily enter the food chain. Most of the copper is in immobile
      fraction at Delhi while at other sites, a sizable portion (10-30%) is found in
      carbonate fraction thus posing medium risk for the aquatic environment.
      Fractionation pattern of zinc shows low to medium risk to aquatic environment.

PMID- 14723926
TI  - Treatment of pulp mill and oil sands industrial wastewaters by the partial spray
      freezing process.
AB  - The spray freezing process, a natural freezing technology, was used to treat pulp
      mill effluent and oil sands tailings pond water. The wastewaters froze partially
      or completely (i.e. with or without runoff generation) during the spraying
      operation. Greater than 60% impurity reduction in the spray ice was obtained when
      30% of the total volume of the sprayed water was released as runoff. Organic and
      inorganic contaminants were rejected with different efficiencies. The impurities
      were uniformly distributed within the ice columns when the spray ice was produced
      without generating any runoff. While a significant increase in impurity
      concentration was observed at the bottom of the ice formed with runoff
      production. The spray freezing process is an effective and economically feasible
      technique for wastewater treatment in cold regions. To achieve higher impurity
      removal efficiency, the wastewater should be only partially frozen during spray
      ice production.

PMID- 14723927
TI  - Removal of coliphages in secondary effluent by microfiltration-mechanisms of
      removal and impact of operating parameters.
AB  - The efficacy of a microfiltration (MF) pilot plant in removing somatic coliphages
      (referred hereafter as coliphages) present in the secondary effluent was
      evaluated during this study. The impact of operating parameters such as feed
      coliphage concentrations, permeate flux and membrane fouling on the removal of
      coliphages by the MF plant was investigated. The study showed that membrane
      fouling was beneficial for removing coliphages by MF. It was also shown that the
      removal of coliphages by MF was initially governed by adsorption on membrane
      surface or in membrane pores. As the membrane fouled, however, the removal of
      coliphages was primarily governed by direct interception on the cake layer formed
      on the surface of the membrane. Increases in feed coliphage concentrations
      resulted in the passage of larger numbers of coliphages when the MF was clean but
      had little impact on the passage of coliphages when the membrane became fouled.
      Increasing permeate flux lowered log-removal values (LRVs) for the clean membrane
      but resulted in an initial increase in LRVs for the fouled membrane followed by a
      drop in LRVs with further increases in permeate flux.

PMID- 14723928
TI  - Metal ions removal from wastewater or washing water from contaminated soil by
      ultrafiltration-complexation.
AB  - In the present paper a process for removal of ions from wastewater or from
      washing water of contaminated soil by using the weakly basic water-soluble
      polymer polyethylenimine (PEI) as chelating agent and the Cu(2+) ion as model in
      combination with an ultrafiltration process was investigated. The complexing
      agent was preliminarily tested to establish the best operative conditions of the
      process. Next, ultrafiltration tests by using five different membranes were
      realised to check membrane performance like flux and rejection. Finally, the
      possibility for recovering and recycling the polymer was tested in order to
      obtain an economically sustainable process. Obtained results showed that
      complexation conditions depends on pH: indeed, at a pH>6 PEI-Cu(2+) complexes are
      formed, while at pH<3 the decomplexation reaction takes place. Saturation
      condition is 0.333 mg Cu(2+)/mg PEI, meaning a ratio PEI/Cu(2+)=3(w/w). UF tests
      showed good results using the PAN 40 kDa membrane reaching an average copper
      concentration in the permeate of 2 mg/l and a flux of 135.4 and 156.5l/h.m(2) at
      2 and 4 bar, respectively. Metal rejection, permeate flow rate, and possibility
      to regenerating and recycling the polymer makes the polymer-assisted
      ultrafiltration process (PAUF) very interesting for metal ion removal from
      waters.

PMID- 14723929
TI  - Removal of soft deposits from the distribution system improves the drinking water
      quality.
AB  - Deterioration in drinking water quality in distribution networks represents a
      problem in drinking water distribution. These can be an increase in microbial
      numbers, an elevated concentration of iron or increased turbidity, all of which
      affect taste, odor and color in the drinking water. We studied if pipe cleaning
      would improve the drinking water quality in pipelines. Cleaning was arranged by
      flushing the pipes with compressed air and water. The numbers of bacteria and the
      concentrations of iron and turbidity in drinking water were highest at 9 p.m.,
      when the water consumption was highest. Soft deposits inside the pipeline were
      occasionally released to bulk water, increasing the concentrations of iron,
      bacteria, microbially available organic carbon and phosphorus in drinking water.
      The cleaning of the pipeline decreased the diurnal variation in drinking water
      quality. With respect to iron, only short-term positive effects were obtained.
      However, removing of the nutrient-rich soft deposits did decrease the microbial
      growth in the distribution system during summer when there were favorable warm
      temperatures for microbial growth. No Norwalk-like viruses or coliform bacteria
      were detected in the soft deposits, in contrast to the high numbers of
      heterotrophic bacteria.

PMID- 14723930
TI  - Quantification of fecal coliform inputs to aquatic systems through soil leaching.
AB  - In order to assess the fecal contamination of rivers in the Seine watershed
      through soil leaching, 78 small streams located in rural areas were sampled
      upstream from any wastewater outfall. Culturable fecal coliforms (FC) and beta-D
      glucuronidase activity (specific of Escherichia coli) were measured in the
      samples. Data showed a significant correlation between both estimates of fecal
      contamination. In the two different areas of the Seine river watershed
      investigated, most of the small streams were significantly contaminated by fecal
      bacteria. In general, the streams flowing through areas partly or fully covered
      with pastures were more contaminated than those flowing through forest and
      cultivated areas. Rainfall increased the suspended solid content of small streams
      as well as their fecal contamination, as an important fraction of FC was adsorbed
      on particles. Calculations showed that, at a large watershed scale, the input of
      FC in rivers through soil leaching was very low when compared to the input
      through the discharge of treated domestic wastewater but this could not be true
      at local scale.

PMID- 14723931
TI  - Long-term effects of operating temperature and sulphate addition on the
      methanogenic community structure of anaerobic hybrid reactors.
AB  - The diversity, population dynamics, and activity profiles of methanogens in
      anaerobic granular sludges from two anaerobic hybrid reactors treating a molasses
      wastewater both mesophilically (37 degrees C) and thermophilically (55 degrees C)
      during a 1081 day trial were determined. The influent to one of the reactors was
      supplemented with sulphate, after an acclimation period of 112 days, to determine
      the effect of competition with sulphate-reducing bacteria on the methanogenic
      community structure. Sludge samples were removed from the reactors at intervals
      throughout the operational period and examined by amplified ribosomal DNA (rDNA)
      restriction analysis (ARDRA) and partial sequencing of 16S rRNA genes. In total,
      18 operational taxonomic units (OTUs) were identified, 12 of which were
      sequenced. The methanogenic communities in both reactors changed during the
      operational period. The seed sludge and the reactor biomass sampled during
      mesophilic operation, both in the presence and absence of sulphate, was
      characterised by a predominance of Methanosaeta spp. Following temperature
      elevation, the dominant methanogenic sequences detected in the non-sulphate
      supplemented reactor were closely related to Methanocorpusculum parvum. By
      contrast, the dominant OTUs detected in the sulphate-supplemented reactor upon
      temperature increase were related to the hydrogen-utilising methanogen,
      Methanobacterium thermoautotrophicum. The observed methanogenic community
      structure in the reactors correlated with the operational performance of the
      reactors during the trial and with physiological measurements of the reactor
      biomass. Both reactors achieved chemical oxygen demand (COD) removal efficiencies
      of over 90% during mesophilic operation, with or without sulphate
      supplementation. During thermophilic operation, the presence of sulphate resulted
      in decreased reactor performance (effluent acetate concentrations of >3000 mg/l
      and biogas methane content of <25%). It was demonstrated that methanogenic
      conversion of acetate at 55 degrees C was extremely sensitive to inhibition by
      sulphide (50% inhibition at 8-17 mg/l unionised sulphide at pH 7.6-8.0), while
      the conversion of H(2)/CO(2) methanogenically was favoured. The combination of
      experiments carried out demonstrated the presence of specific methanogenic
      populations during periods of successful operational performance.

PMID- 14723932
TI  - Submerged yeast fermentation of acid cheese whey for protein production and
      pollution potential reduction.
AB  - Bench-scale batch bioreactors were used to study the effectiveness of cheese whey
      fermentation for single-cell protein production using the yeast Kluyveromyces
      fragilis in reducing the pollution potential of whey as measured by solids,
      chemical oxygen demand (COD) and nitrogenous compounds concentrations. The four
      principal phases (lag, exponential, stationary and death) encountered in the
      history of a microbial culture grown under batch conditions were clearly
      recognized in the growth, temperature and dissolved oxygen curves. The lactose
      concentration and soluble COD displayed three distinct phases corresponding to
      the lag, exponential and stationary phases of the yeast growth. The minimum
      dissolved oxygen and maximum temperature observed in this study (at an air flow
      of 3 VVM, a mixing speed of 400 rpm and an ambient temperature) were 2.49 mg/L
      and 31.6 degrees C, respectively. About 99% of lactose (90.6% of soluble COD) was
      utilized after 28 h. The total COD continued to decline due to cell death
      resulting in a reduction of 42.98%. The total nitrogen concentration remained
      unchanged while the organic nitrogen increased during the exponential phase and
      then declined during the death phase. The ash content remained unchanged while a
      substantial reduction (56%) of the volatile solids was observed. These results
      indicated that sufficient oxygen for yeast growth was present in the medium and
      no cooling system was needed for this type of fermenter under similar
      experimental conditions. Recovering the yeast biomass with ultrafiltration
      reduced the total COD by 98% of its initial value in the raw whey.

PMID- 14723933
TI  - Seasonal and diurnal variations of temperature, pH and dissolved oxygen in
      advanced integrated wastewater pond system treating tannery effluent.
AB  - Seasonal and diurnal fluctuations of pH, dissolved oxygen (DO) and temperature
      were investigated in a pilot-scale advanced integrated wastewater pond system
      (AIWPS) treating tannery effluent. The AIWPS was comprised of advanced
      facultative pond (AFP), secondary facultative pond (SFP) and maturation pond (MP)
      all arranged in series. The variations of pH, DO and temperature in the SFP and
      MP followed the diurnal cycle of sunlight intensity. Algal photosynthesis being
      dependent on sunlight radiation, its activity reached climax at early afternoons
      with DO saturation in the SFP and MP in excess of over 300% and pH in the range
      of 8.6-9.4. The SFP and MP were thermally stratified with gradients of 3-5
      degrees C/m, especially, during the time of peak photosynthesis. The thermal
      gradient in the AFP was moderated by convective internal currents set in motion
      as a result of water temperature differences between the influent wastewater and
      contents of the reactor. In conclusion, the AFP possessed remarkable ability to
      attenuate process variability with better removal efficiencies than SFP and MP.
      Hence its use as a lead treatment unit, in a train of ponds treating tannery
      wastewaters, should always be considered.

PMID- 14723934
TI  - Integrated biofilter-immersed membrane system for the treatment of humic waters.
AB  - An integrated biofilter-immersed membrane study was conducted to determine the
      effect of placing a biofilter before or after a membrane for the treatment of a
      humic type water. The parameters measured included total organic carbon (TOC),
      organic acids, and specific ultraviolet absorbance (SUVA). The difference in
      membrane fouling and microbial growth for the two configurations was also
      examined. Greater TOC and organic acid removal occurred when the biofilter was
      located ahead of the membrane. The greatest decrease in SUVA values was
      associated with the membrane. The membrane located after the biofilter fouled at
      a slower rate than the membrane ahead of the biofilter. Fouling was slower when
      turbidity was present in the synthetic feedwater. A new method is proposed for
      determining the operational cleaning frequency of membranes, using an empirical
      model.

PMID- 14723935
TI  - Evaluation of natural and enhanced PCP biodegradation at a former pesticide
      manufacturing plant.
AB  - Pentachlorophenol (PCP) has been used in the past as a pesticide, herbicide,
      antifungal agent, bactericide, and wood preservative. Thus, PCP is among the most
      ubiquitous chlorinated compounds found in groundwater contamination. A former
      pesticide manufacturing plant located in southern Taiwan has been identified as a
      PCP spill site. In this study, groundwater samples collected from the PCP site
      were analyzed to assess the occurrence of natural PCP biodegradation. Microcosm
      experiments were conducted to (1) evaluate the feasibility of biodegrading PCP by
      indigenous microbial consortia under aerobic and cometabolic conditions, and (2)
      determine the potential of enhancing PCP biodegradation using cane molasses and
      biological sludge cake as the substitute primary substrates under cometabolic
      conditions. The inocula used in this microcosm study were aquifer sediments
      collected from the PCP site and activated sludges collected from the municipal
      and industrial wastewater treatment plants. Results from this field investigation
      indicate that the natural biodegradation of PCP is occurring and causing the
      decrease in PCP concentration. Microcosm results show that the indigenous
      microorganisms can biodegrade PCP under both aerobic and aerobic cometabolism
      conditions. A PCP-degrading bacterium was isolated from the collected aquifer
      sediments and identified as Pseudomonas mendocina NSYSU via some biochemical
      tests and further conformation of DNA sequencing. In batch cultures, P. mendocina
      NSYSU used PCP as its sole source of carbon and energy. The isolated bacterium,
      P. mendocina NSYSU, was capable of completely degrading PCP as indicated by the
      increase in biomass formation with the decrease in PCP concentrations occurred in
      the carbon-free medium simultaneously. Results indicate that the in situ or on
      site aerobic bioremediation using indigenous microorganisms or inoculated
      bacteria would be a feasible technology to clean up the studied PCP-contaminated
      site. Results from this study will be useful in designing a scale-up in situ or
      on-site PCP bioremediation system (e.g., on-site bioreactor) for field
      application.

PMID- 14723936
TI  - Chlorate and nitrate reduction pathways are separately induced in the perchlorate
      respiring bacterium Dechlorosoma sp. KJ and the chlorate-respiring bacterium
      Pseudomonas sp. PDA.
AB  - The effect of nitrate on perchlorate and chlorate reduction by perchlorate
      respiring bacteria (PRB), and on chlorate reduction by chlorate-respiring
      bacteria (CRB), is not well understood, particularly with respect to the
      induction of pathways used to degrade these different chemicals. Based on kinetic
      data obtained in a series of batch tests, we determined that perchlorate
      respiratory enzymes were inducible (by chlorate or perchlorate) and separate from
      those used for denitrification by PRB strain Dechlorosoma sp. KJ. Aerobically
      grown cultures of KJ had lag times of greater than 0.3-2 days when transferred to
      a medium containing only perchlorate, chlorate, or nitrate as an electron
      acceptor. There were no lag times for transfers between identical media. Washed
      cells reduced very little nitrate (<10%) when grown only on chlorate or
      perchlorate. When grown on nitrate, they degraded little chlorate or perchlorate.
      The same lack of activity with these electron acceptors was also observed using
      cell extracts and methyl viologen as an electron carrier, indicating a lack of
      reactivity was not due to failure of the chemical to diffuse into the cell. Taken
      together, these results indicated that enzymes for perchlorate and nitrate
      reduction are separately expressed in strain KJ. The presence of small amounts of
      nitrate in contaminated groundwater may actually help to increase rates of
      perchlorate reduction once the nitrate is completely removed. When strain KJ was
      pre-grown on nitrate and perchlorate, perchlorate degradation (in the absence of
      nitrate) was more rapid compared to cells grown only on perchlorate. Pseudomonas
      sp. PDA was unable to degrade perchlorate or grow using nitrate, and the
      induction of enzymes necessary for chlorate respiration differed for strains KJ
      and PDA. While chlorate reductase and chlorite dismutase activity were induced in
      KJ by chlorate or perchlorate under anaerobic conditions, these two enzymes were
      constitutively expressed by PDA under anaerobic and aerobic conditions
      independent of the presence of chlorate. To our knowledge, this is the first
      report of constitutive expression of both chlorate reductase and chlorite
      dismutase in a bacterium.

PMID- 14723937
TI  - Performance of a sub-surface flow constructed wetland in polishing pre-treated
      wastewater-a tropical case study.
AB  - This paper reports on the performance of three units of a sub-surface horizontal
      flow constructed wetland (CW) pilot plant in polishing effluent from the upflow
      anaerobic sludge blanket (UASB) reactor plant. Studies on the use of UASB for on
      site wastewater pre-treatment were initiated in Tanzania for the first time in
      1993, while initial research works on the application of CW for polishing
      effluent from UASB, the results of which are reported in this paper began in
      1999. In this study the UASB reactor plant received and pre-treated part of the
      wastewater from the student's hostels at the University College of Lands and
      Architectural Studies in Tanzania. Out of the three units, unit B was planted
      with Phragmites mauritianus, unit C with Typha latifolia and A was used as a
      control. Both P.mauritianus and T.latifolia have been extensively researched in
      Europe and USA as suitable species of vegetation in CW. However, very limited
      studies on the suitability of these wetland plants have been reported under
      tropical climate. The studied parameters were chemical oxygen demand (COD),
      nitrate (NO(3)-N), nitrite (NO(2)-N), ammonium (NH(4)-N), faecal coliforms (FC),
      total coliforms (TC), pH, temperature and dissolved oxygen (DO). The study was
      carried out at an average hydraulic retention time of 1.93 days (1.85 in unit A,
      1.96 in unit B and 1.99 in unit C) obtained as a ratio of the volume of
      wastewater in the wetland and the volumetric flow rate of wastewater through the
      wetland unit while taking into consideration the porosity of the media. Better
      performance for the vegetated units B and C were obtained compared to the control
      unit A. Nutrients were least removed in all units (NH(4)-N 11.2%, 25.2% and 23%
      in units A, B and C, respectively, NO(3)-N 32.2%, 40.3% and 44.3% for units A, B
      and C, respectively, and NO(2)-N 23.9%, 38.5% and 23.1% for units A, B and C,
      respectively). The COD removal rate was 33.6%, 56.3% and 60.7% for units A, B and
      C, respectively. The study also indicated that pH increased from the influent to
      the effluent and that DO increase was related to the decrease of temperature. FC
      and TC removal ranged from 43% to 72%, with the least removal in unit A.

PMID- 14723938
TI  - Seawater induced release and transformation of organic and inorganic phosphorus
      from river sediments.
AB  - This paper reports an investigation of the release of organic and inorganic
      phosphorus from a riverine sediment subjected to salinity conditions typical of
      estuarine mixing. Freshwater sediment was mixed with filtered river water in a
      thermostatted reactor, and allowed to equilibrate under aerobic conditions for 3
      days. Salinity was then increased in a stepwise manner by addition of filtered
      low-nutrient seawater over a period of 4 days. A control experiment was performed
      in a second reactor by substituting ultrapure water for seawater. Using a flow
      injection analysis method for measurement of filterable reactive phosphorous
      (FRP, the so-called inorganic fraction) and filterable organic phosphorous (FOP),
      it was found that rapid releases of both FOP and FRP occurred at salinities of
      >/=10 per thousand. Over the 4-day experimental period, sediment release
      increased the filterable P concentration by approx. 50 microgL(-1), and of this,
      nearly half was initially present as FOP, which subsequently underwent rapid
      mineralisation to FRP. The observed behaviour may be explained by a combination
      of salinity induced plasmolysis of sediment bacteria and ion exchange by
      suspended sediment particles.

PMID- 14723939
TI  - Cadmium(II) and zinc(II) adsorption by the aquatic moss Fontinalis antipyretica:
      effect of temperature, pH and water hardness.
AB  - The biosorption of cadmium(II) and zinc(II) ions onto dried Fontinalis
      antipyretica, a widely spread aquatic moss, was studied under different values of
      temperature, initial pH and water hardness. The equilibrium was well described by
      Langmuir adsorption isotherms. Maximum biosorption capacity of cadmium was
      independent on temperature and averaged 28.0 mg g(-1) moss, whereas for zinc,
      capacity increased with temperature, from 11.5 mg g(-1) moss at 5 degrees C to
      14.7 mg g(-1) moss at 30 degrees C. Optimum adsorption pH value was determined as
      5.0 for both metal ions. Cadmium uptake was unaffected by the presence of calcium
      ions, but zinc sorption was improved when water hardness increased from 101.1 to
      116.3 mg CaCO(3)l(-1). Inversely, as hardness increases, the competition with
      calcium ions strongly reduces the affinity of the biosorbent for zinc.

PMID- 14723940
TI  - Modelling bacterial water quality in streams draining pastoral land.
AB  - A model has been developed to predict concentrations of the faecal bacteria
      indicator E. coli in streams draining grazed hill-country in New Zealand. The
      long-term aim of the modelling is to assess effects of land management upon
      faecal contamination and, in the short term, to provide a framework for field
      based research. A daily record of grazing livestock is used to estimate E. coli
      inputs to a catchment, and transport of bacteria to the stream network is
      simulated within surface and subsurface flows. Deposition of E. coli directly to
      streams is incorporated where cattle have access to them, and areas of permanent
      saturation ('seepage zones') are also represented. Bacteria are routed down the
      stream network and in-stream processes of deposition and entrainment are
      simulated. Die-off, both on land and in water, is simulated as a function of
      temperature and solar radiation. The model broadly reproduces observed E. coli
      concentrations in a hill-country catchment grazed by sheep and beef cattle,
      although uncertainty exists with a number of the processes represented. The model
      is sensitive to the distance over which surface runoff delivers bacteria to a
      stream and the amount of excretion direct to streams and onto seepage zones.
      Scenario analysis suggests that riparian buffer strips may improve bacterial
      water quality both by eliminating livestock defaecation in and near streams, and
      by trapping of bacteria by the riparian vegetation.

PMID- 14723941
TI  - The preparation of TiO2 nanometer photocatalyst film by a hydrothermal method and
      its sterilization performance for Giardia lamblia.
AB  - The photocatalytic property of TiO(2) is utilized to sterilize the Giardia
      lamblia in an aqueous solution in this study. The TiO(2) colloidal solution used
      for the film was prepared by the modified hydrothermal method and it was directly
      coated on a UV-lamp, which was set up using a photoreactor manufactured in our
      laboratory. The TiO(2) film was very stably attached to the UV-lamp, and it was
      transparent until 5-time coating. The size of the TiO(2) particle in the film was
      distributed around 20-30 nm and the film thickness was about 200 nm per 1-time
      coating. The G. lamblia cell was just partially damaged under UV-irradiation
      without a TiO(2) photocatalyst, but the dead cell became very small and the dead
      body finally disappeared with an increase in the intensity of UV-irradiation
      after 2 h. In addition, under the TiO(2)/UV-irradiation system, the sterilized
      (dead) rate of G. lamblia was very fast. The sterilizing power increased at lower
      pH in the initial step, but it rather increased at a higher pH in the final step.
      And the sterilization of G. lamblia was very sensitive to the temperature, and
      resulted in an increase in the sterilized rate at higher temperatures. On the
      basis of these experimental observations, it can be concluded that TiO(2)
      photocatalyst under UV-irradiation could be adopted as one of the sterilization
      modalities for the G. lamblia.

PMID- 14723942
TI  - Mobilisation of heavy metals by deicing salts in a roadside environment.
AB  - The seasonal variations of some selected heavy metals (Cd, Cu, Pb and Zn) and
      principal anions in soil solutions were monitored as a function of distance from
      the road at two field sites in Sweden. During the winter, the conductivity,
      concentrations of dissolved sodium and chloride increased dramatically due to the
      application of deicing agents (i.e. NaCl). Due to ion exchange, the pH decreased
      one unit in the soil solutions, whereas the concentrations of total organic
      carbon decreased due to coagulation and/or sorption to stationary solids. The
      heavy metal concentrations increased during the winter, but through different
      mechanisms. Cadmium concentrations in the aqueous phase increased as a response
      to ion exchange, possibly also enhanced by the formation of chloride complexes.
      Similarly, the concentrations of zinc increased, due to ion exchange, with
      calcium and protons. The mechanisms of mobilisation for copper and lead were not
      that clear probably due to association with coagulated or sorbed organic matter
      in combination with colloid dispersion.

PMID- 14723943
TI  - Effects of chlorine on the decrease of estrogenic chemicals.
AB  - The effects of chlorination on the elimination of three estrogenic chemicals such
      as 17beta-estradiol, nonylphenol and bis-phenol A were investigated using yeast
      two-hybrid assay (YTA), estrogen receptor (ER) competition assay (ER-CA), and
      high-performance liquid chromatography/mass spectrometry (LC/MS). The results of
      YTA, ER-CA and the analysis of LC/MS indicated that the estrogenic activity of
      the above-mentioned three endocrine disruptors were significantly reduced as a
      result of chlorination. The decrease in estrogenic activity paralleled a decrease
      in estrogenic chemicals under the influence of free chlorine. One common
      characteristic of estrogenic chemicals is the presence of a phenolic ring.
      Considering that a phenolic ring is likely to undergo some sort of transformation
      in an aqueous chlorination solution, the above-mentioned results may be applied
      to the rest of the estrogenic chemicals in natural waters.

PMID- 14723944
TI  - Artificial groundwater treatment: biofilm activity and organic carbon removal
      performance.
AB  - The artificial recharge of sand aquifers with raw source waters is a means both
      explored and utilised by many water utilities to meet the future potable water
      demands for increasing urban populations. The microbial ecology within these
      systems is however, poorly understood, as is the role that microbial biofilms
      play in the quality of finished water. Knowledge of the ability of biofilm
      bacteria to metabolise natural organic matter (NOM) is limited, particularly in
      respect to the degradation of normally recalcitrant hydrophilic and hydrophobic
      humic acid fractions by sessile and planktonic microbial consortia within sand
      aquifer systems. To simulate the artificial recharge of sand aquifers that were
      proposed for the Greater Stockholm Area, four separate 4 m deep sand columns were
      fed raw lake water and examined over a 45-week study period. The simulated
      aquifer system (hydraulic retention time 9-16 h) demonstrated the removal of
      total organic carbon (TOC) (10+/-5%), direct total counts (DTC) of bacteria (74+/
      11%), heterotrophic plate count (HPC) bacteria (87+/-5%) and assimilable organic
      carbon (AOC) (87+/-5%), thereby fulfilling an important barrier function, except
      for the removal of TOC. Hydrophilic humic acid fractions were more readily
      metabolised by microbiota (HPC and EUB338-positive cells) harvested from the raw
      source water (SSM-W), whilst hydrophobic humic acid fractions promoted higher
      activity by microbiota harvested from the sand matrix (SSM-S). The apparent low
      activity demonstrated by biofilm microbiota (approximately 40% and 25% of DTC
      were positive to EUB338 probing for sand matrix and slide biofilms, respectively)
      could be attributed to the highly recalcitrant nature of the organic loads,
      whilst at the same time explain the poor removal of TOC. Following nutrient
      activation (by the PAC assay) nonetheless, a 3-fold increase in the percentage of
      EUB-positive bacteria was observed on glass slides. Furthermore, the incubation
      of SSM-S with R2A increased probe-active cells from 57+/-8% to 75+/-7% of DTC and
      at the same time increased SSM-W from 38+/-8% to 50+/-10%. Whilst these results
      may imply a good potential for the biological treatment of water by shallow sand
      aquifers, further work should address the poor removal of TOC observed in this
      study.

PMID- 14723945
TI  - Experimental and modelling study on the uptake and desorption kinetics of 133Ba
      by suspended estuarine sediments from southern Spain.
AB  - Dispersion of pollutants in aquatic environments depends on their uptake by
      suspended solids. This work deals with the uptake kinetics of 133Ba (gamma
      emitter and a good analogue of 226Ra) by suspended estuarine sediments (which can
      be resuspended into the water column under certain conditions). This study
      presents a wide set of tracing experiments, including second tracing, decantation
      and desorption processes. The purpose is to characterize 133Ba uptake by
      sediments and to investigate the use and limitations of box models in order to
      describe the uptake kinetics. Water and sediment samples were collected in the
      Huelva estuary (Spain), where environmental 226Ra concentrations have been
      increased by two phosphate fertilizer industries. Samples were characterized by
      granulometric, organic carbon content, cation exchange capacity and XRF-EP
      analyses. Results revealed three-step kinetics, with characteristic times of
      minutes, hours and days. These results enabled the selection and calibration of a
      suitable box model and facilitated the testing of its use as a fully predictive
      tool.

PMID- 14723946
TI  - Clarification of municipal sewage with ferric chloride: the nature of coagulant
      species.
AB  - The nature of coagulant species formed in the system ferric chloride/municipal
      sewage was explored with Transmission Electron Microscopy coupled with Energy
      Dispersive X-ray Spectroscopy (TEM-EDXS) and Fe K-edge X-ray Absorption
      spectroscopy. Jar-test data combined with chemical analysis of supernatant
      (dissolved organic carbon, iron, and phosphorus) and Fourier-Transform-Infrared
      spectroscopy (FTIR) of freeze-dried sediment, provided a detailed description of
      sewage clarification. The results showed that the nature of coagulant species
      evolves with Fe concentration. Up to the optimum turbidity removal, mainly iron
      dimers linked with one phosphate anion are detected. At higher dosages, polymers
      of hydrolyzed Fe appear even though PO(4) still participates in the formation of
      coagulant species. TEM observation of freeze-dried sediments corroborates such an
      evolution of Fe speciation. EDXS analyses reveal that minute amounts of sulfur,
      silicon, aluminum, and calcium, are associated with the coagulant species. Even
      though the coagulant species change with Fe concentration, the destabilization
      mechanism, inferred from electrophoretic mobility of aggregates and the evolution
      of floc size under cyclic changes of stirring conditions, is equivalent with a
      charge neutralization of sewage colloids in the whole range of coagulant
      concentration.

PMID- 14723947
TI  - Bioconcentration and redeposition of polychlorinated biphenyls by zebra mussels
      (Dreissena polymorpha) in the Hudson River.
AB  - The potential impact of zebra mussel infestation on the dynamics of
      polychlorinated biphenyls (PCBs) in the Hudson River was determined by
      investigating the biodeposition and bioconcentration of PCBs, using algal food
      contaminated with 2,5,2'- and 2,4,2',4'-chlorobiphenyls (CBPs) in the laboratory.
      Approximately 46-90% of the total food was ingested depending on the supply rate.
      The highest proportion of ingested congeners was found in biodeposits (64+/-11%
      for 2,5,2'-CBP, and 52+/-6% for 2,4,2',4'-CBP), followed by tissues (17+/-3% for
      2,5,2'-CBP, and 23+/-5% for 2,4,2',4'-CBP), and the lowest in shells. The
      clearance rate decreased with increasing food concentration, but increased with
      dilution rate. On the other hand, ingestion rate (IR) increased with food
      concentration and dilution rate. IR also increased with food supply rate (food
      concentrationxdilution rate) following the same linear function whether the
      supply rate was varied through food concentration or dilution rate. Therefore,
      the dilution rate- or food concentration-dependent variation in IR was due to the
      change in the food supply rate. IR was independent of the kind of PCB congeners.
      The trend of bioaccumulation in mussel tissues from food ingestion was similar to
      that of IR; bioaccumulation increased linearly with food supply rate, whether the
      supply rate was varied through the dilution rate or the food concentration. The
      bioaccumulation of 2,4,2',4'-CBP was significantly higher than that of 2,5,2'-CBP
      (p<0.05). The bioaccumulation was linearly related to the IR or to the total
      amount of food ingested. Assimilation efficiency, PCB incorporated in the tissue
      per total ingested PCB, was higher for 2,4,2',4'-CBP than for 2,5,2'-CBP
      (p<0.05). The congener concentration in biodeposits increased with food supply
      rate. However, the concentration of 2,5,2'-CBP was significantly greater than
      that of 2,4,2',4'-CBP in a mirror image of bioaccumulation. These results
      indicate that zebra mussels may significantly alter PCB dynamics in the Hudson
      River through redeposition from the water column and through bioconcentration.

PMID- 14723948
TI  - Selective wet-air oxidation of diluted aqueous ammonia solutions over supported
      Ni catalysts.
AB  - Wet-air oxidation (WAO) of diluted aqueous ammonia solutions over Ni supported on
      Al(2)O(3) catalysts was investigated. A nitrogen selectivity of approximately 90%
      was achieved by the WAO of ammonia over the 20-wt% Ni/Al(2)O(3) catalyst at 503K,
      a reaction time of 2h and air-feed pressure of 2.0MPa without the dissolution of
      Ni during the reaction. Ni/Al(2)O(3) pretreated by calcinations in air at 1173K
      for 4h showed high stability due to the formation of a NiAl(2)O(4) phase.

PMID- 14723949
TI  - A model for predicting dissolved organic carbon distribution in a reservoir water
      using fluorescence spectroscopy.
AB  - A number of water treatment works (WTW) in the north of England (UK) have
      experienced problems in reducing the dissolved organic carbon (DOC) present in
      the water to a sufficiently low level. The problems are experienced in
      autumn/winter when the colour increases and the coagulant dose at the WTW needs
      to be increased in order to achieve sufficient colour removal. However, the DOC
      content of the water varies little throughout the year. To investigate this
      further, the water was fractionated using resin adsorption techniques into its
      hydrophobic (fulvic and humic acid fractions) and hydrophilic (acid and non-acid
      fractions) components. The fractionation process yields useful information on the
      changing concentration of each fraction but is time consuming and labour
      intensive. Here, a method of rapidly determining fraction concentration was
      developed using fluorescence spectroscopy. The model created used synchronous
      spectra of fractionated material compared against bulk water spectra and
      predicted the fraction concentrations to within 10% for a specific water. The
      model was unable to predict fraction concentrations for waters from a different
      watershed.

PMID- 14723951
TI  - Discovery, characterization and SAR of gambogic acid as a potent apoptosis
      inducer by a HTS assay.
AB  - Gambogic acid (2), a natural product isolated from the resin of Garcinia hurburyi
      tree, was discovered to be a potent apoptosis inducer using our cell- and caspase
      based high-throughput screening assays. Gambogic acid was found to have an EC(50)
      of 0.78 microM in the caspase activation assay in T47D breast cancer cells. The
      apoptosis-inducing activity of gambogic acid was further characterized by a
      nuclear fragmentation assay and flow cytometry analysis in human breast tumor
      cells T47D. Gambogic acid was found to induce apoptosis independent of cell
      cycle, which is different from paclitaxel that arrests cells in the G2/M phase.
      To understand the structure-activity relationship (SAR) of gambogic acid,
      derivatives of 2 with modifications to different function groups were prepared.
      SAR studies of gambogic acid, as measured by the caspase activation assay, showed
      that the 9,10 carbon-carbon double bond of the alpha,beta-unsaturated ketone is
      important for biological activity, while the 6-hydroxy and 30-carboxy group can
      tolerate a variety of modifications. The importance of the 9,10 carbon-carbon
      double bond was confirmed by the traditional growth inhibition assay. The high
      potency of 2 as an inducer of apoptosis, its novel mechanism of action, easy
      isolation and abundant supply, as well as the fact that it is amenable to
      chemical modification, makes gambogic acid an attractive molecule for the
      development of anticancer agents.

PMID- 14723952
TI  - Muscarinic M2 antagonists: anthranilamide derivatives with exceptional
      selectivity and in vivo activity.
AB  - Anthranilamide analogues such as 23 are potent and highly selective muscarinic M2
      antagonists that also show good oral bioavailability and in vivo activity.

PMID- 14723953
TI  - Thalidomide analogues demonstrate dual inhibition of both angiogenesis and
      prostate cancer.
AB  - The identification of agents with antiproliferative activity against endothelial
      cells has significant value for the treatment of many angiogenesis-dependent
      pathologies. Herein, we describe the discovery of a series of thalidomide
      analogues possessing inhibitory effects against both endothelial and prostate
      cancer cells. More specifically, several analogues exhibited low micromolar to
      mid-nanomolar potency in the inhibition of human microvascular endothelial cell
      (HMEC) proliferation, both in the presence and absence of vascular endothelial
      growth factor (VEGF), with the tetrafluorophthalimido class of compounds
      demonstrating the greatest potency. Additionally, all the compounds were screened
      against two different androgen independent prostate cancer cell lines (PC-3 and
      DU-145). Again, the tetrafluorophthalimido analogues exhibited the greatest
      effect with GI(50) values in the low micromolar range. Thalidomide was found to
      demonstrate selective inhibition of androgen receptor positive LNCaP prostate
      cancer cells. Furthermore, we showed that, as an example, tetrafluorophthalimido
      analogue 19 was able to completely inhibit the prostate specific antigen (PSA)
      secretion by the LNCaP cell line, while thalidomide demonstrated a 70%
      inhibition. We have also demonstrated that a correlation exists between HMEC and
      prostate cancer cell proliferation for this structural class. Altogether, our
      study suggests that these analogues may serve as promising leads for the
      development of agents that target both androgen dependent and independent
      prostate cancer and blood vessel growth.

PMID- 14723954
TI  - Structure-activity relationships of globomycin analogues as antibiotics.
AB  - Globomycin (1a), a signal peptidase II inhibitor, and its derivatives show potent
      antibacterial activity against Gram-negative bacteria. The synthesis and
      antimicrobial activity of novel globomycin analogues are reported. The hydroxyl
      group in the L-Ser residue was essential for the antimicrobial activity and the
      length of the alkyl side chain greatly influenced the activity. In addition,
      derivatives that had a modified cyclic core exhibited weak activity. One of the
      analogues showed a wider antimicrobial spectrum, effective against not only Gram
      negative but also Gram-positive bacteria.

PMID- 14723955
TI  - Metabolism of 5'alpha,8'-cycloabscisic acid, a highly potent and long-lasting
      abscisic acid analogue, in radish seedlings.
AB  - We synthesized 5'alpha,8'-cycloabscisic acid (CycloABA), a highly potent and long
      lasting abscisic acid (ABA) analogue, by a different method from that reported
      before. CycloABA fed to radish seedlings had more metabolic tolerance than ABA.
      The major metabolite of CycloABA was the glucose conjugate, which was the minor
      metabolite of ABA. The 8'-hydroxylated metabolite and its cyclized isomer, which
      were major metabolites of ABA, were not found as metabolites of CycloABA. The
      present results suggest that the highly potent and long-lasting activity of
      CycloABA is caused by resistance to ABA 8'-hydroxylase, and that CycloABA is
      partially metabolized to the glucose conjugate by ABA glucosyltransferase.

PMID- 14723956
TI  - N-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor
      antagonists: analysis of structure-activity relationships for the "C-Region".
AB  - We recently reported that N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]
      thiourea (2) was a high affinity antagonist of the vanilloid receptor with a
      binding affinity of K(i)=63 nM and an antagonism of K(i)=53.9 nM in rat VR1
      heterologously expressed in Chinese hamster ovary (CHO) cells (Mol. Pharmacol.
      2002, 62, 947-956). In an effort to further improve binding affinity and
      antagonistic potency, we have modified the C-region of the lead 4-t-butylbenzyl
      group with diverse surrogates, such as araalkyl, alkyl, 4-alkynylbenzyl, indanyl,
      3,3-diarylpropyl, 4-alkoxybenzyl, 4-substituted piperazine and piperidine. The
      lipophilic surrogates, arylalkyl and alkyl, conferred modest decreases in binding
      affinities and antagonistic potencies; the groups having heteroatoms resulted in
      dramatic decreases. Our findings indicate that 4-t-butylbenzyl is one of the most
      favorable groups for high receptor binding and potent antagonism to VR1 in this
      structural series.

PMID- 14723958
TI  - Synthesis, biological evaluation, and structural studies on N1 and C5 substituted
      cycloalkyl analogues of the pyrazole class of CB1 and CB2 ligands.
AB  - A series of N1 and C5 substituted cycloalkyl and C5 4-methylphenyl analogues of
      the N-(piperidin-1-yl)-4-methyl-1H-pyrazole-3-carboxamide class of cannabinoid
      ligands were synthesized. The analogues were evaluated for CB1 and CB2 receptor
      binding affinities and receptor subtype selectivity. The effects of pyrazole
      substitution on ligand conformation and as such receptor affinities was not
      readily apparent; therefore, the geometries of the N1 and C5 substituents
      relative to the pyrazole ring were studied using high field NMR spectroscopy and
      systematic molecular mechanics geometry searches. An analysis of the relative
      ring geometries and functional group orientations provides new insight into the
      structural requirements of the CB1 and CB2 ligand binding pocket.

PMID- 14723957
TI  - Synthesis and anti-inflammatory evaluation of 4-anilinofuro[2,3-b]quinoline and 4
      phenoxyfuro[2,3-b]quinoline derivatives. Part 3.
AB  - Mast cells, neutrophils and macrophages are important inflammatory cells that
      have been implicated in the pathogenesis of acute and chronic inflammatory
      diseases. To explore a novel anti-inflammatory agent, we have synthesized certain
      4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives and
      evaluated their anti-inflammatory activities by reaction of 3,4-dichlorofuro[2,3
      b]quinoline with appropriate Ar-NH(2) or Ar-OH. Compounds 6a and 15 were proved
      to be more potent than the reference inhibitor, mepacrine for the inhibition of
      rat peritoneal mast cell degranulation with IC(50) values of 6.5 and 16.4 microM,
      respectively. Compounds 2b, 6a, 10, and 15 also showed potent inhibitory activity
      (IC(50)=7.2-29.4 microM) for the secretion of lysosomal enzyme and beta
      glucuronidase from neutrophils. These results also indicated that oxime
      derivatives are more potent than the respective ketone precursors (6a> or =2a;
      7a> or =3), and the substituent such as Me at the oxime decreased inhibitory
      activity (6a> or =6b; 7a> or =7b). Among these derivatives, compound 6a showed
      the most potent activity with IC(50) values of 6.5-11.6 microM for the inhibition
      of mast cell degranulation and neutrophil degranulation.

PMID- 14723959
TI  - Synthesis, biological, and chiroptical activity of 3-phenyl-clavams.
AB  - The [2+2]cycloaddition of chlorosulfonyl isocyanate to simple vinyl ethers
      derived from the 2-O-sulfonylated (R) and (S) 1-phenyl-1,2-ethanediol leads to 4
      alkoxy-azetidin-2-ones with a moderate stereoselectivity. The cycloaddition to
      analogous (Z)-propenyl ethers proceeds stereospecifically with the retention of
      the olefin configuration. The intramolecular alkylation of beta-lactam nitrogen
      atom furnished all possible stereoisomers of 3-phenyl- and 6-methyl-3-phenyl
      clavams. The biological and chiroptical activity of synthesized clavams was
      investigated. The (3R,5R)-diastereomer 30 showed higher inhibition of bacterial
      enzymes than other related compounds.

PMID- 14723960
TI  - Syntheses and receptor-binding studies of derivatives of the opioid antagonist
      naltrexone.
AB  - Naltrexone (1), which is a member of the group of competitive opioid antagonists,
      shows a strong affinity for mu-receptors and its derivatives have been notable as
      novel receptor antagonists. In this paper, the preparation of several naltrexone
      derivatives is described; these were used to investigate the role of the
      oxygenated functional groups in facilitating binding to a series of the opioid
      receptors. The derivatives showed affinity for opioid mu-receptors which was
      similar to that of naltrexone, but these compounds, which had masked hydroxyl
      functional groups, displayed a moderate activity. These results suggest that
      every oxygenated functional group in naltrexone (1) plays an important role in
      binding to the opioid receptor.

PMID- 14723961
TI  - Design, synthesis and structure-affinity relationships of aryloxyanilide
      derivatives as novel peripheral benzodiazepine receptor ligands.
AB  - Since the peripheral benzodiazepine receptor (PBR) has been primarily found as a
      high-affinity binding site for diazepam in rat kidney, numerous studies of it
      have been performed. However, the physiological role and functions of PBR have
      not been fully elucidated. Currently, we presented the pharmacological profile of
      two high and selective PBR ligands, N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2
      phenoxyphenyl)acetamide (7-096, DAA1106) (PBR: IC(50)=0.28 nM) and N-(4-chloro-2
      phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (7-099, DAA1097) (PBR: IC(50)=0.92
      nM). The compounds are aryloxyanilide derivatives, and identified with known PBR
      ligands such as benzodiazepine (1, Ro5-4864), isoquinoline (2, PK11195),
      imidazopyridine (3, Alpidem), and indole (5, FGIN-1-27) derivatives. The
      aryloxyanilide derivatives, which have been derived by opening the diazepine ring
      of 1, are a novel class as PBR ligands and have exhibited high and selective
      affinity for peripheral benzodiazepine receptors (PBRs). These novel derivatives
      would be useful for exploring the functions of PBR. In this paper, the design,
      synthesis and structure-affinity relationships of aryloxyanilide derivatives are
      described.

PMID- 14723962
TI  - The alkaloids and other constituents from the root and stem of Aristolochia
      elegans.
AB  - Two new aristolactams, aristolactam E (1) and aristolactam-AIIIa-6-O-beta-D
      glucoside (2), three novel benzoyl benzyltetrahydroisoquinoline ether N-oxide
      alkaloids, aristoquinoline A (3), aristoquinoline B (4), and aristoquinoline C
      (5), and a new biphenyl ether, aristogin F (6), together with 62 known compounds
      have been isolated from the root and stem of Aristolochia elegans Mast. The
      structures of the new natural products were established on the basis of spectral
      evidence. Some of the isolated compounds were examined for their antioxidative
      and antityrosinase activities. Occurrence of the isoquinolones, biphenyl ethers,
      and benzoyl benzyltetrahydroisoquinoline ether alkaloids in the same plant
      indicated the definite possibility of these metabolites as biotransformation
      intermediates of bisbenzyltetrahydroisoquinoline alkaloids. This can be useful to
      solve the catabolic process of bisbenzyltetrahydroisoquinoline alkaloids.

PMID- 14723963
TI  - Combining NMR and molecular modelling in a drug delivery context: investigation
      of the multi-mode inclusion of a new NPY-5 antagonist bromobenzenesulfonamide
      into beta-cyclodextrin.
AB  - NMR spectroscopic and molecular modelling methods have been employed to describe
      the complexation of trans-N-4-[N'-(4
      chlorobenzoyl)hydrazinocarbonyl]cyclohexylmethyl-4-bromobenzenesulfonamide, a new
      chemotype of NPY-5 antagonist, and beta-cyclodextrin, revealing the coexistence
      of two different kinds of 1:1 complexes where conformational changes of the guest
      compound with respect to the free state are also detected.

PMID- 14723965
TI  - Interaction of isofraxidin with human serum albumin.
AB  - This study was designed to examine the interaction of isofraxidin with human
      serum albumin (HSA) under physiological conditions with drug concentrations in
      the range of 3.3 x 10(-6) mol L(-1)-3.0x10(-5) mol L(-1) and HSA concentration at
      1.5 x 10(-6) mol L(-1). Fluorescence quenching methods in combination with
      Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD)
      spectroscopy were used to determine the drug-binding mode, the binding constant
      and the protein structure changes in the presence of isofraxidin in aqueous
      solution. Spectroscopic evidence showed that the interaction results in one type
      of isofraxidin-HSA complex with binding constants of 4.1266 x 10(5) L mol(-1),
      3.8612 x 10(5) L mol(-1), 3.5063 x 10(5) L mol(-1), 3.1241 x 10(5) L mol(-1) at
      296 K, 303 K, 310 K, 318 K, respectively. The thermodynamic parameters, enthalpy
      change (DeltaH) and entropy change (DeltaS) were calculated to be -10.08 kJ mol(
      1) and 73.57 J mol(-1) K(-1) according to van't Hoff equation, which indicated
      that hydrophobic interaction played a main role in the binding of isofraxidin to
      HSA. The experiment results are nearly in accordance with the calculation results
      obtained by Silicon Graphics Ocatane2 workstation.

PMID- 14723964
TI  - Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and
      cytotoxic activities.
AB  - Derivatives based on a benzotropolone skeleton (9-26) have been prepared by the
      enzymatic coupling (horseradish peroxidase/H2O2) of selected pairs of compounds
      (1-8), one with a vic-trihydroxyphenyl moiety, and the other with an ortho
      dihydroxyphenyl structure. Some of these compounds have been found to inhibit TPA
      induced mice ear edema, nitric oxide (NO) synthesis, and arachidonic acid release
      by LPS-stimulated RAW 264.7 cells. Their cytotoxic activities against KYSE 150
      and 510 human esophageal squamous cell carcinoma and HT 29 human colon cancer
      cells were also evaluated.

PMID- 14723966
TI  - Aplysia californica mediated cyclisation of novel 3'-modified NAD+ analogues: a
      role for hydrogen bonding in the recognition of cyclic adenosine 5'-diphosphate
      ribose.
AB  - Cyclic ADP-ribose mobilizes intracellular Ca2+ in a variety of cells. To
      elucidate the nature of the interaction between the C3' substituent of cADP
      ribose and the cADPR receptor, three analogues of NAD+ modified in the adenosine
      ribase (xyloNAD+ 3'F-xyloNAD+ and 3'F-NAD+ were chemically synthesised from D
      xylose and adenine starting materials. 3'F-NAD+ was readily converted to cyclic
      3'F-ADP ribose by the action of the cyclase enzyme derived from the mollusc
      Aplysia californica. XyloNAD+ and 3'F-xyloNAD+ were cyclised only reluctantly and
      in poor yield to afford unstable cyclic products. Biological evaluation of cyclic
      3'F-ADP ribose for calcium release in sea urchin egg homogenate gave an EC(50) of
      1.5+/-0.5 microM. This high value suggests that the ability of the C3'
      substituent to donate a hydrogen bond is crucial for agonism.

PMID- 14723967
TI  - Three-dimensional quantitative structure-activity relationship analyses of
      piperidine-based CCR5 receptor antagonists.
AB  - The CCR5 chemokine receptor has recently been found to play a crucial role in the
      viral entry stage of HIV infection and has therefore become an attractive
      potential target for anti-HIV therapeutics. On the other hand, the lack of CCR5
      crystal structure data has impeded the development of structure-based CCR5
      antagonist design. In this paper, we compare two three-dimensional Quantitative
      Structure-Activity Relationship (3D-QSAR) methods: Comparative Molecular Field
      Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA)
      on a series of piperidine-based CCR5 antagonists as an alternative approach to
      investigate the interaction between CCR5 antagonists and their receptor.
      Superimposition of antagonist structures was performed using two alignment rules:
      atomic/centroid rms fit and rigid body field fit techniques. The 3D QSAR models
      were derived from a training set of 72 compounds, and were found to have
      predictive capability for a set of 19 holdout test compounds. The resulting
      contour maps produced by the best CoMFA and CoMSIA models were used to identify
      the structural features relevant to biological activity in this series of
      compounds. Further analyses of these interaction-field contour maps also showed a
      high level of internal consistency.

PMID- 14723968
TI  - Alpha-hydroxyketones as inhibitors of urease.
AB  - A variety of alpha-hydroxyketones (1-13) and alpha-diketones (14-20) were
      evaluated for their effect on the jack bean urease. Of 13 alpha-hydroxyketones (1
      13) tested, 2,2'-thenoin (10) (IC(50)=0.18 mM), furoin (9) (IC(50)=0.36 mM), 2
      hydroxy-1-phenylethanone (5) (IC(50)=0.47 mM) and acetol (1) (IC(50)=2.9 mM)
      showed potent inhibitory activity against the enzyme, comparable with hydroxyurea
      (IC(50)=0.1 mM). The inhibitory effects were completely blocked by 2
      mercaptoethanol or dithiothreitol. A nickel ion influenced the inhibitory effects
      of 5 and 9 in a dose-dependent manner, but not of 1 and 10. On the other hand,
      the corresponding alpha-diketones such as 2,2'-thenil (20), furil (19) and
      PhCOCHO (14) exhibited little or no ability to inhibit the urease. We have
      demonstrated for the first time that some alpha-hydroxyketone derivatives show
      urease inhibitory activity, possibly by binding to cysteinyl residues in the
      active site.

PMID- 14723969
TI  - Dihydropyridine neuropeptide Y Y1 receptor antagonists 2. bioisosteric urea
      replacements.
AB  - Structure-activity studies around the urea linkage in BMS-193885 (4a) identified
      the cyanoguanidine moiety as an effective urea replacement in a series of
      dihydropyridine NPY Y(1) receptor antagonists. In comparison to urea 4a (K(i)=3.3
      nM), cyanoguanidine 20 (BMS-205749) displayed similar binding potency at the Y(1)
      receptor (K(i)=5.1 nM) and full functional antagonism (K(b)=2.6 nM) in SK-N-MC
      cells. Cyanoguanidine 20 also demonstrated improved permeability properties in
      Caco-2 cells in comparison to urea 4a (43 vs 19 nm/s).

PMID- 14723970
TI  - Newly discovered tachykinins raise new questions about their peripheral roles and
      the tachykinin nomenclature.
AB  - The tachykinin family has recently been extended by the discovery of a third
      tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1,
      endokinin A and endokinin B) that have a widespread peripheral distribution and a
      tachykinin NK(1) receptor selectivity. This and the identification of other
      tachykinin-like peptides such as C14TKL-1 and virokinin raise many questions
      about the roles played by tachykinins in peripheral tissues and render terms such
      as 'neurokinins' and 'SP receptor' inappropriate.

PMID- 14723971
TI  - Pharmacological basis of 'Yang-invigoration' in Chinese medicine.
AB  - The 'Yin-Yang' theory is an ancient Chinese philosophy that underlies the
      practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost
      body function possibly through enhancing the mitochondrial oxidative processes,
      the Yin property (i.e. antioxidant potential) of these herbs can also play a role
      in safeguarding mitochondrial ATP generation. The pharmacological basis of 'Yang
      invigoration' by Chinese tonic herbs might be due primarily to the enhancement of
      mitochondrial ATP generation.

PMID- 14723972
TI  - Are all NSAIDs other than 'coxibs' really equal?

PMID- 14723973
TI  - Organellar junctions promote targeted Ca2+ signaling in smooth muscle: why two
      membranes are better than one.
AB  - Numerous cellular processes are regulated by fluctuations in the concentration of
      a single cation, Ca(2+). To accomplish this feat, cells have developed mechanisms
      that target Ca(2+) signals to specific effectors in both space, by strategically
      localizing effectors and ion-transporting molecules, and time, by encoding the
      regulation of the frequency of Ca(2+) oscillations. With an emphasis on smooth
      muscle, we have analyzed how the interaction of Ca(2+) transporters located on
      closely apposing membranes of the plasma membrane, sarcoplasmic reticulum and
      mitochondria provides the structural foundation for site-specific and time
      specific Ca(2+) signaling. These junctional membrane complexes can either control
      the concentration of Ca(2+) in the microdomain that surrounds an effector
      molecule or deliver Ca(2+) from the translocator on one membrane to a second
      translocator on the opposing membrane without significant diffusion into the bulk
      cytosol, an event we term 'linked Ca(2+) transport'.

PMID- 14723974
TI  - Targeting of ion channels to membrane microdomains: localization of KV channels
      to lipid rafts.
AB  - Voltage-gated K(+) channels are an important determinant of cellular excitability
      and key components of multiple signal transduction pathways. However, relatively
      little is known about the mechanisms of K(V) channel localization or their
      membrane partitioning. Lipid rafts are specialized membrane microdomains that are
      rich in sphingolipids and cholesterol. These rafts have been implicated in the
      organization of many membrane-associated signaling pathways and are currently the
      focus of intense interest in the scientific community. Biochemical and functional
      evidence indicate that K(V) channels, in addition to other ion channels, localize
      to lipid raft microdomains on the cell surface. Although several important
      questions regarding specific mechanisms of channel localization remain, emerging
      data indicate that protein-lipid interactions should be considered as a new
      mechanism of ion channel localization and compartmentation that might permit the
      therapeutic modulation of channel properties via alteration in membrane lipids.

PMID- 14723975
TI  - Therapeutic siRNAs.
AB  - The ability of small-interfering RNAs (siRNAs) to silence gene expression in
      somatic mammalian cells has provided researchers with a novel tool to block the
      expression of disease-causing genes, provided that their mRNA sequences are
      known. siRNAs can be delivered to cells either exogenously as synthetic agents or
      endogenously as gene-encoding siRNAs. Recent studies demonstrate the general
      application of siRNAs to silence gene expression in a range of cell types and in
      whole mammals. Beyond their value for dissecting gene functions and target
      validation, siRNAs also hold great potential as gene-specific therapeutic agents.

PMID- 14723976
TI  - From the street to the brain: neurobiology of the recreational drug gamma
      hydroxybutyric acid.
AB  - gamma-Hydroxybutyric acid (GHB) is a short-chain fatty acid that occurs naturally
      in the mammalian brain and is formed primarily from the precursor gamma
      aminobutyric acid (GABA). The properties of GHB suggest that it has a
      neuromodulatory role in the brain and has the ability to induce several
      pharmacological and behavioral effects. GHB has been used clinically as an
      anesthetic and to treat alcoholism and narcolepsy. Furthermore, GHB has emerged
      recently as a major recreational drug of abuse. GHB appears to have dual
      mechanisms of action in the brain. Biochemical data suggest that the intrinsic
      neurobiological activity of GHB might be mediated through the GHB receptor, which
      is separate and distinct from the GABA(B) receptor. However, many of the
      pharmacological and clinical effects of exogenously administered GHB, including
      the properties of addiction, tolerance, withdrawal and intoxication, are probably
      mediated via the GABA(B) receptor, where GHB might act both directly as a partial
      agonist and indirectly through GHB-derived GABA.

PMID- 14723977
TI  - Regulated ubiquitination of proteins in GPCR-initiated signaling pathways.
AB  - The transmission of information through G-protein-coupled receptor (GPCR)
      initiated signaling pathways is modulated in several ways. Although
      phosphorylation of some of the proteins that populate these pathways is a well
      known modulatory process, recent studies have shown that signaling proteins can
      also undergo regulated ubiquitination in response to GPCR activation, with
      diverse consequences. To date, three GPCRs, some of their associated proteins and
      certain downstream mediators, notably inositol (1,4,5)-trisphosphate
      [Ins(1,4,5)P(3)] receptors, have been shown to be ubiquitinated following GPCR
      activation. Regulated ubiquitination causes proteasomal degradation of
      Ins(1,4,5)P(3) receptors and appears to control GPCR endocytosis and trafficking.
      Defining the roles of ubiquitination in GPCR-mediated signaling is an important
      task because novel drugs that perturb the ubiquitin-proteasome pathway are now
      being approved as therapeutic agents.

PMID- 14723978
TI  - Current pharmacological treatments for nicotine dependence.
AB  - There are nearly 1.1 billion users of nicotine and tobacco products worldwide.
      Tobacco use through cigarette smoking is the leading preventable cause of death
      in the world and kills nearly four million people annually. However, although
      some cigarette smokers are able to quit, many are not, and standard medications
      to assist in smoking cessation (e.g. nicotine-replacement therapies and sustained
      release bupropion) are ineffective in many remaining smokers. Recent developments
      in our understanding of the neurobiology of nicotine dependence have identified
      several neurotransmitter systems that might contribute to the process of smoking
      maintenance and relapse, including dopamine, noradrenaline, 5-hydroxytryptamine,
      acetylcholine, endogenous opioids, GABA, glutamate and endocannabinoids. Several
      existing medications are being tested as treatments for nicotine dependence and
      novel investigational agents are under development as effective treatments for
      nicotine dependence in the 'hard to treat' tobacco user.

PMID- 14723979
TI  - Progress towards hormonal male contraception.
AB  - The use of androgens is an essential part of all experimental approaches to
      hormonal male contraception and involves the suppression of gonadotrophins,
      leading to inhibition of spermatogenesis. Although clinical trials have proven
      the concept of hormonal male contraception, their modalities have been
      unacceptable for practical use for several reasons. Because the efficacy of all
      self-administered androgen preparations has been disappointing, recent studies
      have focused on either androgen implants or injectable, long-acting testosterone
      esters such as testosterone undecanoate. However, in contrast to East Asian men,
      only two-thirds of Caucasian men respond to such androgen-based regimens with the
      desired azoospermia (no sperm produced), and thus additional agents are required.
      Over the past decades various combinations of androgen preparations with
      different progestins or gonadotrophin-releasing-hormone antagonists have been
      tested in clinical trials. Of these, testosterone administered in combination
      with either depot medroxyprogesterone acetate, norethisterone enanthate,
      desogestrel or etonogestrel have shown promising efficacy.

PMID- 14723980
TI  - Towards evidence to secure reproductive rights.

PMID- 14723981
TI  - The Lancet's policy on conflicts of interest--2004.

PMID- 14723982
TI  - Drug combinations for malaria: time to ACT?

PMID- 14723983
TI  - Assessing inequalities in maternal mortality.

PMID- 14723984
TI  - Enterobacter sakazakii--new foods for thought?

PMID- 14723985
TI  - Clinical value of the X chromosome in testicular germ-cell tumours.

PMID- 14723986
TI  - Vascular higher-level gait disorders--a step in the right direction?

PMID- 14723987
TI  - Artesunate combinations for treatment of malaria: meta-analysis.
AB  - BACKGROUND: Addition of artemisinin derivatives to existing drug regimens for
      malaria could reduce treatment failure and transmission potential. We assessed
      the evidence for this hypothesis from randomised controlled trials. METHODS: We
      undertook a meta-analysis of individual patients' data from 16 randomised trials
      (n=5948) that studied the effects of the addition of artesunate to standard
      treatment of Plasmodium falciparum malaria. We estimated odds ratios (OR) of
      parasitological failure at days 14 and 28 (artesunate combination compared with
      standard treatment) and calculated combined summary ORs across trials using
      standard methods. FINDINGS: For all trials combined, parasitological failure was
      lower with 3 days of artesunate at day 14 (OR 0.20, 95% CI 0.17-0.25, n=4504) and
      at day 28 (excluding new infections, 0.23, 0.19-0.28, n=2908; including re
      infections, 0.30, 0.26-0.35, n=4332). Parasite clearance was significantly faster
      (rate ratio 1.98, 95% CI 1.85-2.12, n=3517) with artesunate. In participants with
      no gametocytes at baseline, artesunate reduced gametocyte count on day 7 (OR
      0.11, 95% CI 0.09-0.15, n=2734), with larger effects at days 14 and 28. Adding
      artesunate for 1 day (six trials) was associated with fewer failures by day 14
      (0.61, 0.48-0.77, n=1980) and day 28 (adjusted to exclude new infections 0.68,
      0.53-0.89, n=1205; unadjusted including reinfections 0.77, 0.63-0.95, n=1958). In
      these trials, gametocytes were reduced by day 7 (in participants with no
      gametocytes at baseline 0.11, 0.09-0.15, n=2734). The occurrence of serious
      adverse events did not differ significantly between artesunate and placebo.
      INTERPRETATION: The addition of 3 days of artesunate to standard antimalarial
      treatments substantially reduce treatment failure, recrudescence, and gametocyte
      carriage.

PMID- 14723988
TI  - Dihydroartemisinin-piperaquine against multidrug-resistant Plasmodium falciparum
      malaria in Vietnam: randomised clinical trial.
AB  - BACKGROUND: Southeast Asia has the most resistant malaria parasites in the world,
      which severely limits treatment options. There is general acceptance that to
      combat resistance, combinations of antimalarial drugs that include an artemisinin
      derivative should be used, and, if possible, these should be formulated in a
      single tablet. METHODS: We did a pilot randomised study in a tertiary referral
      hospital in Vietnam to compare the efficacy of 3-day regimens of
      dihydroartemisinin-trimethoprim-piperaquine (DHA-TP total dose 4.8/13.6/48 mg/kg,
      respectively) with the standard antimalarial regimen in Vietnam, artesunate
      mefloquine (A3M total dose 12/25 mg/kg, respectively) in non-immune patients with
      uncomplicated Plasmodium falciparum malaria. 114 patients were randomised, 76 to
      DHA-TP and 38 to A3M. The subsequent open randomised trial at a Provincial Health
      Station compared DHA-TP, dihydroartemisinin-piperaquine, and A3M in 400 patients.
      In both studies all patients received directly observed therapy and were followed
      up for 56 days. The primary endpoint was reappearance of P falciparum malaria
      within 56 days of treatment. Analysis was by intention to treat. FINDINGS: The 56
      day cure rate in the pilot study, adjusted for reinfections identified by PCR
      genotyping, was 97.4% (74/76) in the DHA-TP group and 100% (38/38) in the A3M
      group. In the second study, cure rates were similar in the three groups; DHA-TP
      97.4% (153/157), dihydroartemisinin-piperaquine 98.7% (164/166), and A3M 98.7%
      (76/77). The DHA-TP and dihydroartemisinin-piperaquine regimens were well
      tolerated; fewer than 3% of patients had side-effects that might have been
      related to treatment, compared with 16% of A3M patients (p<0.001). No patients
      were lost to follow-up. INTERPRETATION: Dihydroartemisinin-piperaquine is an
      inexpensive, safe, highly efficacious fixed-dose antimalarial combination
      treatment that could make an important contribution to the control of multidrug
      resistant falciparum malaria.

PMID- 14723990
TI  - The familial technique for linking maternal death with poverty.
AB  - BACKGROUND: Recognition of the synergy between health and poverty is now apparent
      in the development strategies of many low-income countries, and markers are
      needed to monitor progress towards poverty-relevant goals. Maternal mortality has
      been proposed as a possible candidate but evidence is lacking on the link with
      poverty at the level of individuals. We introduce a new approach to exploring the
      relation--the familial technique. METHODS: We used data from 11 household surveys
      in ten developing countries to create percentage distributions of women according
      to their poverty-related characteristics and survival status (alive, non-maternal
      death, maternal death). These women were identified as the sisters of the adult
      female respondents in the surveys, and were assigned the same poverty status as
      their respondent sibling. FINDINGS: The analysis showed significant associations,
      across a diverse set of countries, between women's poverty status (proxied by
      educational level, source of water, and type of toilet and floor) and survival.
      These associations indicated a gradient within and across the survival
      categories. With increasing poverty, the proportion of women dying of non
      maternal causes generally increased, and the proportion dying of maternal causes
      increased consistently. Further analysis reported here for one of the countries-
      Indonesia, revealed that about 32-34% of the maternal deaths occurred among women
      from the poorest quintile of the population. The risk of maternal death in this
      country was around 3-4 times greater in the poorest than the richest group.
      INTERPRETATION: This new method makes efficient use of existing survey data to
      explore the relation between maternal mortality and poverty, and has wider
      potential for examining the poor-rich gap.

PMID- 14723991
TI  - Loss of glutamine synthetase in the human epileptogenic hippocampus: possible
      mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy.
AB  - BACKGROUND: High extracellular glutamate concentrations have been identified as a
      likely trigger of epileptic seizures in mesial temporal lobe epilepsy (MTLE), but
      the underlying mechanism remains unclear. We investigated whether a deficiency in
      glutamine synthetase, a key enzyme in catabolism of extracellular glutamate in
      the brain, could explain the perturbed glutamate homoeostasis in MTLE. METHODS:
      The anteromedial temporal lobe is the focus of the seizures in MTLE, and surgical
      resection of this structure, including the hippocampus, leads to resolution of
      seizures in many cases. By means of immunohistochemistry, western blotting, and
      functional enzyme assays, we assessed the distribution, quantity, and activity of
      glutamine synthetase in the MTLE hippocampus. FINDINGS: In western blots, the
      expression of glutamine synthetase in the hippocampus was 40% lower in MTLE than
      in non-MTLE samples (median 44 [IQR 30-58] vs 69 [56-87]% of maximum
      concentration in standard curve; p=0.043; n=8 and n=6, respectively). The enzyme
      activity was lower by 38% in MTLE vs non-MTLE (mean 0.0060 [SD 0.0031] vs 0.0097
      [0.0042] U/mg protein; p=0.045; n=6 and n=9, respectively). Loss of glutamine
      synthetase was particularly pronounced in areas of the MTLE hippocampus with
      astroglial proliferation, even though astrocytes normally have high content of
      the enzyme. Quantitative immunoblotting showed no significant change in the
      amount of EAAT2, the predominant glial glutamate transporter in the hippocampus.
      INTERPRETATION: A deficiency in glutamine synthetase in astrocytes is a possible
      molecular basis for extracellular glutamate accumulation and seizure generation
      in MTLE. Further studies are needed to define the cause, but the loss of
      glutamine synthetase may provide a new focus for therapeutic interventions in
      MTLE.

PMID- 14723992
TI  - Giant coronary aneurysms.

PMID- 14723993
TI  - Subcutaneous echinococcosis of the knee.

PMID- 14723994
TI  - Occurrence of Enterobacter sakazakii in food production environments and
      households.
AB  - Enterobacter sakazakii occasionally causes illness in premature babies and
      neonates. Contamination of infant formulae during factory production or bottle
      preparation is implicated. Advice to health-care professionals focuses on bottle
      preparation, but the effectiveness of prevention depends on the degree of
      contamination and contamination sites, which are generally unknown. To keep
      contamination to a minimum in the finished product depends on knowledge of the
      occurrence of E sakazakii. We used a refined isolation and detection method to
      investigate the presence of this micro-organism in various food factories and
      households. Environmental samples from eight of nine food factories and from five
      of 16 households contained E sakazakii. The widespread nature of this micro
      organism needs to be taken into account when designing preventive control
      measures.

PMID- 14723995
TI  - XIST unmethylated DNA fragments in male-derived plasma as a tumour marker for
      testicular cancer.
AB  - Testicular germ-cell tumours (TGCTs) are the most common malignant diseases among
      men aged 20-40 years. We developed a DNA tumour marker for TGCTs based on the
      unmethylated DNA profile of a neoplasm. The 5' end of the XIST gene is mainly
      hypomethylated in TGCTs irrespective of XIST expression. Male somatic cells,
      however, show complete methylation through the CpG sites, including the minimum
      promoter and XIST-conserved repeats. Identification of a XIST unmethylated
      fragment in male plasma might be diagnostic for TGCTs.

PMID- 14723996
TI  - Transmissible spongiform encephalopathies.
AB  - Nosologically, transmissible spongiform encephalopathies (TSE or prion diseases)
      should be grouped with other neurodegenerative disorders such as Alzheimer's and
      Parkinson's diseases, which are all caused by toxic gain of function of an
      aberrant form of a constitutively expressed protein. Failure to clear these
      proteins from the brain induces neuronal dysfunction. Transmissibility is the
      property that separates TSE from other neurodegenerative diseases, and this
      property seems to reside within the structure of the abnormal protein. The human
      phenotypic range of these encephalopathies includes Creutzfeldt-Jakob disease and
      its variant form, kuru, Gerstmann-Straussler-Scheinker syndrome, and fatal
      familial insomnia. Notwithstanding the generally low incidence of TSE and their
      limited infectiousness, major epidemics such as bovine spongiform encephalopathy
      and kuru arise in situations where intraspecies recycling of the abnormal protein
      is sustained. Moreover, evidence of chronic subclinical infection in animals
      offers insights into pathogenesis and prompts re-evaluation of the notion of
      species barriers and present infection control measures. Since case-to-case
      transmission is the only known mechanism underlying epidemics of TSE, potential
      reservoirs of infectivity in the tails of epidemics need continued vigilance.

PMID- 14723997
TI  - CCN proteins: multifunctional signalling regulators.
AB  - CONTEXT: Although little is known as yet about the processes that coordinate cell
      signalling pathways, matrix proteins are probably major players in this type of
      global control. The CCN (cyr61, ctgf, nov) proteins are an important family of
      matricellular regulatory factors involved in internal and external cell
      signalling. This family participates in angiogenesis, chondrogenesis, and
      osteogenesis, and they are probably involved in the control of cell proliferation
      and differentiation. STARTING POINT: Runping Gao and David Brigstock (Hepatol Res
      2003; 27: 214-20) recently showed that CCN2 (CTGF, connective tissue growth
      factor) is a cell-adhesion factor for hepatic stellate cells. On exposure to
      transforming growth factor beta, hepatic stellate cells produce distinct CCN2
      isoforms. Gao and Brigstock assign to CCN2 module 3 the capacity to mediate
      binding to low-density-lipoprotein receptor-related protein (LRP), which was
      previously reported to interact with CCN2 and to be involved in various types of
      signalling. They also establish that CCN2 binding to LRP is heparin dependent and
      that module 4 of CCN2 promotes LRP-independent adhesion of hepatic stellate
      cells. The differential binding of CCN2 isoforms to LRP highlights the importance
      of functional interactions between individual modules, and reinforces the concept
      that different module combinations might confer agonistic or antagonistic
      activities. WHERE NEXT? It is essential to understand how the distinct
      configuration of the various CCN isoform affects their biological activities and
      bioavailability, and to explore the mechanisms and the regulatory processes
      involved in the production of truncated CCN isoforms. A better understanding of
      the structural basis for their multifunctionality is a prerequisite to wider use
      of CCN proteins in molecular medicine.

PMID- 14723998
TI  - Reproductive health and human rights.

PMID- 14723999
TI  - The right to count.

PMID- 14724000
TI  - Reproductive health without rights in Peru.

PMID- 14724001
TI  - Sexual and reproductive health funding: donors and restrictions.

PMID- 14724002
TI  - Obstetric fistula: the international response.

PMID- 14724003
TI  - Invoking human rights to reduce maternal deaths.

PMID- 14724004
TI  - Making abortion rare and safe.

PMID- 14724005
TI  - New and underused technologies to reduce maternal mortality.

PMID- 14724006
TI  - Forced migrants--turning rights into reproductive health.

PMID- 14724007
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724008
TI  - The Nobel prize for MRI: a wonderful discovery and a sad controversy.

PMID- 14724009
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724010
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724011
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724012
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724014
TI  - Public health implications of world trade negotiations.

PMID- 14724015
TI  - Erythropoietin to treat anaemia in patients with head and neck cancer.

PMID- 14724016
TI  - Public health implications of world trade negotiations.

PMID- 14724017
TI  - Inguinal and incisional hernias.

PMID- 14724019
TI  - Tactile stimulation of insoles and balance control in elderly people.

PMID- 14724020
TI  - Inguinal and incisional hernias.

PMID- 14724021
TI  - Tactile stimulation of insoles and balance control in elderly people.

PMID- 14724023
TI  - The perils of CPOE.

PMID- 14724024
TI  - Inappropriate aggression.

PMID- 14724027
TI  - Jerome Groopman.

PMID- 14724033
TI  - Historical inevitability.

PMID- 14724034
TI  - Mahmoud F Fathalla. Interview.

PMID- 14724035
TI  - Demonstrating the dose- and time-related effects of 7-nitroindazole on picrotoxin
      induced convulsions, memory formation, brain nitric oxide synthase activity, and
      nitric oxide concentration in rats.
AB  - In this study, the dose (50, 100, 150, and 200 mg/kg)- and time (30 and 60 min)-
      related effects of 7-nitroindazole (7-NI), a neuronal specific inhibitor of
      nitric oxide synthase (NOS) were tested on picrotoxin (5 mg/kg)-induced
      convulsions and memory formation in rats. The changes produced by these doses of
      7-NI were determined on NOS activity and nitric oxide (NO) concentration in the
      brain. The effects of 7-NI were tested in animals pretreated (30 min) with L
      arginine (500 and 1000 mg/kg). 7-NI, at 50 and 100 mg/kg, did not produce
      significant changes in NOS activity and NO concentration in the brain and memory
      formation. However, the convulsant action of picrotoxin was inhibited in a dose
      dependent manner in these animals. A time-dependent decrease in the activity of
      NOS and the concentration of NO, a promotion of picrotoxin-induced convulsions,
      and an impairment of memory were found in animals treated with 150 and 200 mg/kg
      of 7-NI. The larger and not the smaller dose of L-arginine raised the
      concentration of NO, inhibited picrotoxin-induced convulsions and promoted memory
      process. Either dose of L-arginine failed to prevent 50 and 100 mg/kg of 7-NI
      from inhibiting convulsions. The effects of the larger doses of 7-NI (150 and 200
      mg/kg) were effectively prevented by the increase of NO and not the ineffective
      dose of L-arginine. These results suggest that 7-NI (50 and 100 mg/kg) decreases
      convulsions by a nonspecific mechanism and that an inhibition of NOS by the
      larger doses of it (150 and 200 mg/kg) results in proconvulsant action and memory
      impairment. The data further show that the margin between the protective and
      proconvulsant doses of 7-NI is relatively narrow. These results have been taken
      together with the earlier reports that 7-NI produces learning impairment and
      fails to increase the anticonvulsant effect of traditional antiepileptic agents
      on experimentally induced convulsions to conclude that 7-NI can never emerge as
      an anticonvulsant agent for clinical use.

PMID- 14724036
TI  - Involvement of serotoninergic mechanism in analgesia by castration and flutamide,
      a testosterone antagonist, in the rat formalin test.
AB  - Several studies have suggested that testosterone has a role in nociception.
      Recently, we have shown that castration and flutamide, a testosterone antagonist,
      induce analgesia in the late phase of formalin test, which is related to increase
      of 5-HT levels in the dorsal horn of the lumbar spinal cord. The aim of the
      present study was to investigate the effect of fluoxetine, a selective serotonin
      reuptake inhibitor, on castration and flutamide-induced analgesia in order to
      further explore the role of 5-HT systems in such analgesia. Four weeks after
      castration, there was an analgesia in the late phase of formalin test, and this
      was potentiated by acute (0.32 mg kg(-1) ip) treatment of fluoxetine.
      Furthermore, coadministration of fluoxetine (0.32 mg kg(-1) ip) and flutamide (10
      mg kg(-1) ip) produced more antinociceptive effect than those animals receiving
      fluoxetine and flutamide alone. The analgesic effect of fluoxetine (0.32 mg kg(
      1) ip) and flutamide (10 mg kg(-1) ip) was abolished by pretreatment with 5,7-DHT
      (100 microg/rat it) and naloxone (2 mg kg(-1) ip). In summary, our data suggest
      that fluoxetine and flutamide have antinociceptive effects in tonic inflammatory
      pain through functional alteration of serotonergic systems, and their effects are
      potentiated by coadministration. The possible role of opioidergic system in their
      antinociceptive effect cannot be neglected.

PMID- 14724037
TI  - Antidepressant-like effects of NMDA-receptor antagonist injected into the dorsal
      hippocampus of rats.
AB  - Exposure to uncontrollable stressors causes behavioral changes that have been
      related to depressive states in humans. Poststress intrahippocampal
      administration of amino-7-phosphonoheptanoic acid (AP-7), a glutamate NMDA
      receptor antagonist, attenuated the restraint-induced decreased exploration of an
      elevated plus maze 24 h later. The objective of the study was to test if this
      treatment would also attenuate the increased immobility seem in the forced swim
      test (FST) due to preexposition to this stressful situation. Male Wistar rats
      with cannulae aimed at the dorsal hippocampus were submitted to 15 min of forced
      swimming and tested 24 h later. They received bilateral intrahippocampal
      injections of AP-7 (10 nmol) either before or after the pretest swimming session
      or before the test. Poststress treatment increased latency to display the first
      episode of immobility and tended to reduce total immobility time. The drug was
      ineffective when given before stress or before test and in nonstressed animals.
      This suggests that glutamate NMDA receptors located in the dorsal hippocampus are
      involved in the behavioral changes observed in the FST.

PMID- 14724038
TI  - Effects of nicotine on elevated plus maze and locomotor activity in male and
      female adolescent and adult rats.
AB  - Over 4500 adolescents start smoking every day in the United States. Of these, one
      third will die prematurely from smoking-related diseases. The current experiment
      examined the effects of repeated-acute nicotine administration (saline, 0.1, 0.5,
      or 1.0 mg/kg daily) on elevated plus maze (EPM) and locomotor behaviors of 160
      adolescent and adult male and female Sprague-Dawley rats. Nicotine's effects
      depended on age and sex of animal. On the EPM, nicotine exerted anxiolytic
      effects (increased percentage of time in the open arms) in adolescent males, but
      exerted anxiogenic effects (decreased percentage of time in the open arms) in
      adolescent females and in adult males and females. For adults, peak locomotor
      activity occurred at the 0.5-mg/kg dosage, and the 1.0-mg/kg dosage reduced
      activity below the saline level on Day 1 and below the 0.5-mg/kg level on Days 1,
      3, and 5. For adolescents, peak locomotor activity occurred at the 1.0-mg/kg
      dosage and there were no activity-depressant effects. These findings suggest
      there are age differences in sensitivity to nicotine that may affect
      vulnerability to long-term tobacco use.

PMID- 14724039
TI  - Naltrexone attenuates acute cigarette smoking behavior.
AB  - This within-subjects, placebo-controlled laboratory study was designed to examine
      the effects of naltrexone on cigarette response in 44 chronic smokers (23 male,
      21 female). Each participant received either 50-mg oral naltrexone or identical
      placebo during the morning of the session after maintaining overnight abstinence.
      Subsequently, the participant was administered a smoking cue (holding lit
      cigarette) to examine craving and associated features of smoking, and instructed
      to smoke a cigarette 1 h later. This was followed by a smoking interval in which
      participants could choose to smoke up to four more cigarettes over a 2-h period.
      Subjective measures (withdrawal, craving, affect, and side effects) and smoking
      behavior were assessed throughout the session. Naltrexone significantly reduced
      the total number of choice cigarettes smoked and expired carbon monoxide levels
      (Ps<.05). Naltrexone significantly increased total side effects, especially for
      sedation (P<.01). Further, naltrexone significantly increased overall negative
      affect, and decreased positive affect 1 h after smoking the first cigarette
      (Ps<.05). However, naltrexone did not affect acute withdrawal or smoking urges.
      Despite mixed findings, women reported more overall naltrexone-induced withdrawal
      (P<.05) and side effects (P<.08) compared to men. Although the exact mechanism is
      unknown, the findings support an opioid antagonist attenuation of smoking
      behavior.

PMID- 14724040
TI  - Effects of opioid dependence and tobacco use on ventilatory response to
      progressive hypercapnia.
AB  - Respiratory depression is a serious medical risk of opioid use. Most opioid
      abusers also smoke cigarettes, perhaps further compromising breathing.
      Differences in ventilatory response to nonhypoxic hypercapnia were studied in
      healthy volunteers with limited substance use (LU), tobacco smokers (SM), and
      opioid-dependent, methadone-maintained smokers (OD). The last two groups had
      similar current cigarette use and all groups were similar in gender and body mass
      index. Because previous data suggest that SM are sensitive to hypoxia but not
      hypercapnia, it was predicted that only the OD group would exhibit decreased
      carbon dioxide (CO(2)) sensitivity. All subjects rebreathed CO(2) during three
      identical sessions (four trials per session). Fractional end-tidal (Fet) CO(2)
      levels during repeated 4-min exposures to progressive hypercapnia (6% to 10%)
      were similar across groups. Ventilatory response (breathing rate, tidal volume
      and minute volume) linearly increased with FetCO(2) concentration and did not
      differ significantly across sessions. Relative to the LU and SM groups (which did
      not significantly differ), the CO(2)-minute volume and CO(2)-breathing rate
      functions were significantly shifted rightward (decrease in intercept but not
      slope) for OD subjects. These data are consistent with the hypothesis that
      chronic opioid exposure and/or short-term methadone maintenance (but not tobacco
      or nicotine use) produces a specific decrease in CO(2) sensitivity, primarily
      through an inhibitory effect on respiratory frequency.

PMID- 14724041
TI  - Sensitivity to the effects of a kappa opioid in rats with free access to exercise
      wheels: differential effects across behavioral measures.
AB  - It is well established that chronic exercise decreases sensitivity to mu opioid
      agonists; however, it is less clear what effects it has on kappa opioids. The
      purpose of the present study was to examine sensitivity to the effects of the
      selective, kappa opioid spiradoline in rats with free access to exercise wheels.
      Rats were obtained at weaning and randomly assigned to either standard
      polycarbonate cages (sedentary) or modified cages equipped with exercise wheels
      (exercise). After approximately 7 weeks under these conditions, sensitivity to
      the effects of spiradoline on tests of antinociception, locomotor activity,
      conditioned place preference, and diuresis were examined in both groups of rats.
      Sedentary rats were more sensitive than exercising rats to the antinociceptive
      effects of spiradoline, and this effect was observed at both low and high
      nociceptive intensities. In contrast, exercising rats were more sensitive than
      sedentary rats to the diuretic effects of spiradoline, and slightly more
      sensitive to spiradoline's effects in the conditioned place preference procedure.
      No differences in sensitivity were observed to the effects of spiradoline on
      locomotor activity. Sensitivity to the antinociceptive effects of spiradoline
      nonsignificantly increased in exercising rats that were reassigned to sedentary
      housing conditions, and changes in spiradoline sensitivity were correlated with
      exercise output in individual subjects. Collectively, these data suggest that
      exercise alters sensitivity to the behavioral effects of kappa opioids, but that
      the direction and magnitude of this effect depends on the behavioral measure
      examined.

PMID- 14724042
TI  - p-Chloroamphetamine blocks physostigmine-induced memory enhancement in rats with
      unilateral nucleus basalis lesions.
AB  - The present experiment examined whether p-chloroamphetamine (PCA), a serotonergic
      releasing/depleting agent, would block the memory-enhancing effect of
      physostigmine in rats with N-methyl-D-aspartic acid (NMDA)-induced unilateral
      lesions of the nucleus basalis of Meynert (uni-nbM). Six groups of subjects with
      uni-nbM lesions in addition to an isolated sham-operated control group were
      included. Subjects were trained and tested 72 h later on a one-trial passive
      avoidance task. Thirty minutes before training, rats with uni-nbM lesions were
      injected with either 1.0 or 5.0 mg/kg PCA or saline. Immediately after training,
      approximately half the subjects in each group were injected with either saline or
      0.06 mg/kg physostigmine. Animals in the sham group received saline injections.
      Saline-injected animals with uni-nbM lesions performed poorly at test, a deficit
      that was reversed with physostigmine. Pretraining injections of PCA blocked
      physostigmine's memory-enhancing effect, although motor impairment during
      training may have contributed to decrements in test performance in animals
      injected with 5.0 mg/kg. Subjects were killed about 10 days later and their
      frontal cortices examined for choline acetyltransferase (ChAT). Results from the
      neurochemical analysis revealed that the lesion decreased ChAT levels and that
      the injection of 1.0 mg/kg PCA exaggerated this lesion-induced depletion.
      Implications for the interaction between acetylcholine and serotonin are
      discussed.

PMID- 14724043
TI  - Acceleration of onset of action in schedule-induced polydipsia: combinations of
      SSRI and 5-HT1A and 5-HT1B receptor antagonists.
AB  - Onset of action is a key unmet need in the treatment of depression. However, very
      few preclinical models in which the effects of antidepressants can be shown are
      suitable for screening for onset. In this context, previous literature suggests
      that a slow onset of action of selective serotonin reuptake inhibitors (SSRIs) is
      observed in schedule-induced polydipsia (SIP). The current investigation was
      performed to determine the latency to reduce SIP of the SSRI, fluoxetine, and of
      two treatments known to facilitate 5-HT neurotransmission to a greater extent
      than an SSRI alone. These treatments included interaction studies for
      fluoxetine+the 5-HT(1A) antagonist, WAY 100635, and for fluoxetine+the 5-HT(1B)
      partial agonist, GR 127935. Food-restricted rats were trained on a fixed interval
      schedule with drinking water freely available. Once water intake was stable, rats
      were randomly assigned to vehicle of treatment groups. Daily treatment was
      continued for 3 (interaction studies) or 18 days (fluoxetine alone study).
      Fluoxetine significantly reduced SIP after 5-6 days of treatment, with the
      maximal effect evidenced after 8 days. WAY 100635 and GR 127935 accelerated the
      onset of action of fluoxetine, with significant effects observed on treatment day
      1. These data suggest that SIP may be useful to assess the onset of action of
      serotonin enhancers.

PMID- 14724044
TI  - The influence of midazolam on active avoidance retrieval and acquisition rate in
      rats.
AB  - The purpose of the present study was to examine the influence of midazolam on the
      retrieval and acquisition rate of two-way active avoidance in rats. In the
      schedule 2 x 100 trials, the effects of midazolam (0.5-5.0 mg/kg), benzodiazepine
      binding site antagonist flumazenil (2.5-10.0 mg/kg), specific antagonist of
      GABA(A) receptor, bicuculline (0.5-4.0 mg/kg), and the blocker of GABA(A)
      receptor containing Cl(-) channels, picrotoxin (1.0-5.0 mg/kg), on the second day
      retrieval of avoidance performance were investigated, as well as the influence of
      the used blockers of GABA(A) receptor function on midazolam effects. Furthermore,
      the effect of midazolam (1.0 mg/kg) on acquisition rate in the 5 x 50 schedule,
      as well as the effects of third day treatment changing in that paradigm, was
      examined. Throughout the study, drugs were given intraperitoneally, 30 min before
      testing. Midazolam at the dose of 1.0 mg/kg facilitated avoidance retrieval,
      whereas flumazenil and bicuculline did not significantly change behavior.
      Picrotoxin (5.0 mg/kg) diminished performance. All three kinds of blockers used
      abolished facilitatory action of midazolam, confirming GABAergic mediation of the
      effect of benzodiazepine. Midazolam (1.0 mg/kg) increased acquisition rate during
      five consecutive days relative to saline, but without significant effect on the
      first day acquisition. In the case of third day changing of treatments, the
      intersection of regression rate lines was detected. Results from active avoidance
      paradigm experimentally support the findings from human studies that in certain
      circumstances, benzodiazepines, potentiating GABAergic neurotransmission, could
      produce retrieval-enhancing effects in memory tasks.

PMID- 14724045
TI  - Comparative anticonvulsant activity of N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline derivatives in rodents.
AB  - The anticonvulsant activity of competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo (F)-quinoxaline (NBQX) and noncompetitive 2,3-benzodiazepines and
      tetrahydroisoquinolines (THIQs) AMPA/kainate receptor antagonists, was tested in
      different experimental seizure models and compared with diazepam, a conventional
      antiepileptic drug acting on GABAergic neurotransmission. In particular, the
      compounds were evaluated against audiogenic and maximal electroshock seizures
      (MES) test and pentetrazol (PTZ) seizures model, and all of them showed
      protective action. In addition, NBQX, 2,3-benzodiazepines and THIQs, but not
      diazepam, were also protective against clonic and tonic seizures and lethality
      induced by kainate, AMPA and ATPA, but were ineffective against NMDA-induced
      seizures. Only 2,3-benzodiazepines and some THIQs were able to affect 4
      aminopyridine- and mercaptopropionic-acid-induced seizures. The duration of
      anticonvulsant action of 33 micromol/kg of some 2,3-benzodiazepines and THIQs was
      also investigated in DBA/2 mice, a strain genetically susceptible to audiogenic
      seizures, and it was observed that the derivative THIQ-10c, possessing an acetyl
      group at the N-2 and a chlorine atom on the C-1 phenyl ring, showed higher
      anticonvulsant activity and longer-lasting protective effects.

PMID- 14724046
TI  - Comparative study on the effects of kynurenic acid and glucosamine-kynurenic
      acid.
AB  - Kynurenic acid (KYNA) is the only known endogenous N-methyl-D-aspartate (NMDA)
      receptor inhibitor and might therefore come into consideration as a therapeutic
      agent in certain neurobiological disorders. However, its use as a neuroprotective
      compound is practically excluded because KYNA does not readily cross the blood
      brain barrier (BBB). We recently synthetized a new compound, glucosamine
      kynurenic acid (KYNA-NH-GLUC), which is presumed to cross the BBB more easily. In
      this study, the effects of KYNA and KYNA-NH-GLUC on behavior and cortical
      activity were investigated in adult rats. The results show that (1) on
      intracerebroventricular application, the behavioral changes induced by KYNA and
      by KYNA-NH-GLUC are quite similar; (2) on intravenous administration, KYNA (25
      mg/kg) has no effect on the somatosensory-evoked cortical potentials, whereas
      KYNA-NH-GLUC (25 mg/kg) causes transient but appreciable reductions in the
      amplitudes of the evoked responses within 5 min after application; and (3) the
      results of in vitro studies demonstrated that both KYNA and KYNA-NH-GLUC reduced
      the amplitudes of the field excitatory postsynaptic potentials (fEPSPs). These
      observations suggest that the two compounds have similar effects, but that KYNA
      NH-GLUC passes the BBB much more readily than does KYNA. These results imply that
      the conjugated NH-GLUC is of importance in the passage across the BBB.

PMID- 14724047
TI  - EEG power spectra and auditory P300 during free smoking and enforced smoking
      abstinence.
AB  - We investigated resting EEG and auditory P300 during free smoking and 36 h of
      enforced smoking abstinence in 12 healthy volunteers. Resting EEG was recorded on
      19 scalp leads and auditory P300 was obtained by an oddball paradigm task.
      Spectral analysis of EEG (absolute and relative power, mean frequency), latency
      and amplitude of auditory P300 were considered for statistical analysis. EEG
      changes were not significant during free smoking but were significant during
      smoking abstinence. Theta absolute power increased by +57% (P<.001), whereas
      alpha and delta absolute power increased by +26% (P<.01) and +19% (P<.01),
      respectively; theta absolute power change was delayed and prolonged. Alpha mean
      frequency reduced by -0.31 Hz (P<.001), whereas delta, theta and beta1 mean
      frequency increased by +0.13 Hz (P<.05), +0.09 Hz (P<.05) and +0.23 Hz (P<.01),
      respectively. Auditory P300 amplitude and latency were unaffected by smoking
      abstinence. Resting EEG, but not auditory P300, was sufficiently sensitive to
      detect changes during enforced smoking abstinence, and EEG bands had different
      temporal changes.

PMID- 14724048
TI  - Effects of nitric oxide on morphine self-administration in rat.
AB  - Previous studies have reported that morphine exerts its effects in part through
      the release of nitric oxide (NO). In the present study, the effects of acute and
      chronic administration of the NO precursor, L-arginine and NO synthase (NOS)
      inhibitor, L-nitro-amino-methyl-ester (L-NAME) on morphine self-administration in
      rats were investigated. The animals were initially trained to press a lever using
      food as reinforcer. Rats were surgically prepared with a chronic Silastic
      catheter implanted in the external jugular vein. Five days after surgery, they
      were trained to press a lever for drug self-administration. The present data
      indicate that L-arginine (0.05, 0.1, and 0.15 mg/kg/injection) but not L-NAME
      (0.05, 0.1, and 0.15 mg/kg/injection) induced self-administration behavior and
      increased locomotion. The response induced by L-arginine (0.1 mg/kg/injection)
      was reduced by pretreatment with L-NAME (5, 10, and 15 mg/kg ip). Both the acute
      (5, 10, and 15 mg/kg ip) and the chronic (200 mg/kg ip; twice daily for 4 days)
      administration of L-arginine reduced morphine self-administration. However, acute
      (5, 10, and 20 mg/kg ip) and chronic (50 mg/kg ip; twice daily for 4 days)
      administration of L-NAME increased morphine self-administration significantly. It
      can be concluded that NO may have a role in morphine self-administration.

PMID- 14724049
TI  - Voluntary exercise augments acute effects of CB1-receptor inverse agonist on body
      weight loss in obese and lean mice.
AB  - Cannabinoid CB1 receptor (CB1R) inverse agonists reduce appetite and body weight
      (BW) gain in various species. Exercise is thought to be a natural reward process
      and the cannabinoid system is also believed to influence reward. We tested the
      hypothesis that voluntary exercise would augment the effects of AM251, a CB1R
      inverse agonist, on food intake (FI) and BW loss in murine genetic models of
      obesity. ob/ob, agouti yellow (A(y)), and lean C57BL/6J mice were treated via
      oral gavage with vehicle or AM251 (1, 3, or 10 mg/kg) 1 h before the dark cycle.
      The suppressive effects of 3 and 10 mg/kg AM251 on overnight FI, BW gain, and
      water intake (WI) were significant in ob/ob mice. In contrast, in A(y) mice, 10
      mg/kg AM251 decreased FI and BW gain while it did not influence WI. Food
      consumption of ob/ob and A(y) mice, as evidenced by feeding frequency (FF) and
      feeding duration (FD), was reduced by AM251 for 4-6 h. AM251 at these doses had
      no impact on the appetitive behavior or BW gain of lean mice. After a 1-week wash
      out period, mice were given running wheels in their home cages. With running
      wheel exercise, lean and obese mice exhibited increased sensitivity to AM251. Low
      voluntary wheel running activity of ob/ob mice precluded detection of combined
      effects of AM251 and exercise in this genetic model of obesity. Lean and agouti
      mice given AM251 combined with exercise lost a greater amount of BW than with
      AM251 alone. Our data suggest that voluntary exercise can enhance CB1R inverse
      agonist effects on appetite and BW loss in both lean and agouti obese mice.

PMID- 14724050
TI  - Early developmental lead exposure increases sensitivity to cocaine in a self
      administration paradigm.
AB  - The purpose of this investigation was to determine if lead exposure during
      pregnancy and nursing alters cocaine sensitivity later in the adult cycle,
      although lead exposure had been discontinued following early development. Female
      rats were exposed via gavage to 0 or 16 mg/kg lead daily for 30 days prior to
      breeding with nonexposed males. The respective daily exposure regimens continued
      throughout gestation and lactation (perinatal lead exposure). Lead exposure was
      discontinued on the day of weaning (postnatal day [PND] 21). Beginning on PND 70,
      male offspring were trained to self-administer cocaine HCl intravenously.
      Examination of a range of cocaine doses (0.030, 0.060, 0.125, 0.250, and 0.500
      mg/kg/infusion) revealed that, as adults, animals exposed to lead during early
      development self-administered cocaine at significantly greater rates at a low
      dose of the drug. In addition, self-administration rates were lower among lead
      exposed animals at higher doses of cocaine. These findings were observed in metal
      exposed animals where blood and brain tissue levels had returned to the levels of
      controls. Collectively, these data suggest that early developmental lead exposure
      may increase sensitivity to cocaine later in the life cycle.

PMID- 14724051
TI  - 5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats.
AB  - Giving L-tryptophan, serotonin's circulating precursor, or a serotonin-releasing
      drug can decrease food intake and body weight. Giving 5-hydroxy-L-tryptophan (5
      HTP), serotonin's immediate intracellular precursor, has been thought to be
      ineffective in enhancing brain serotonin synthesis unless it is coadministered
      with a dopa decarboxylase inhibitor to protect 5-HTP from destruction outside the
      brain. We have examined the effect of 5-HTP on food consumption and tissue 5-HTP
      levels among rats subjected to two different hyperphagic stimuli, food
      deprivation and a standardized stress (tail pinch), and on plasma 5-HTP levels in
      humans. In rats, 5-HTP (3-200 mg/kg ip) suppressed food intake in a dose
      dependent manner in both models, but was at least eight times more effective in
      our stress-hyperphagia model. (Differences in the two procedures might have
      contributed to the observed differences in potencies.) This suppression was
      blocked by coadministration of another large neutral amino acid (LNAA), L-valine.
      Brain 5-HTP levels correlated significantly with peak plasma 5-HTP (r(2)=.69) or
      5-HTP/LNAA (r(2)=.81) levels. Additionally, among humans, oral 5-HTP (1.2-2.0
      mg/kg) produced, after 1 and 2 h, a significant increase in plasma 5-HTP (1.5- to
      2.3-fold). These observations suggest that 5-HTP may be useful in controlling the
      excessive food intake sometimes generated by stress, even if given without
      decarboxylase inhibitors or other drugs.

PMID- 14724053
TI  - Increased homocysteine levels associated with sex and stress in the learned
      helplessness model of depression.
AB  - Elevated levels of homocysteine (Hcy) have been associated with major depressive
      (MD) illness. As human females show a higher predisposition towards depression,
      this study examined how Hcy levels in rats are affected by sex and estrous cycle
      in the learned helplessness (LH) model of depression. Male and female rats in
      either estrus or diestrus were subjected to LH, with intervals of 4 days between
      the two stress tests and between tests and sacrifice, in order to accommodate the
      female estrous cycle. No differences were found in LH behavior between males and
      females at either estrous phase. Control Hcy levels were significantly lower in
      females than in males (-36%, P<.001), with no further differences between estrous
      and diestrus phases in females. Stress exposure increased plasma Hcy by
      approximately 26% in females, both in estrus and diestrus, but not in males.
      However, when behavioral responses to stress were considered, no association was
      found between increased Hcy levels and propensity to develop helpless behavior.
      Therefore, while male rats have higher basal Hcy levels than females, females
      appear to be more vulnerable than males to stress-induced elevations in Hcy,
      although this did not correlate with behavioral responses to stress. Neither was
      this vulnerability influenced by estrous phase. These results imply that both
      stress and sex should be considered as risk factors for increased plasma Hcy.

PMID- 14724052
TI  - Restoration of spontaneous exploratory behaviors with an intrathecal NMDA
      receptor antagonist or a PKC inhibitor in rats with acute pancreatitis.
AB  - The aim of this study was to determine the influence of a glutamate receptor
      antagonist or a protein kinase C (PKC) inhibitor on the central visceral
      nociceptive amplification process present in an experimental pancreatitis model.
      The acute pancreatitis model was produced by combining intraductal infusion of an
      irritative bile salt, glycodeoxycholic acid (GDOC), with intraperitoneal
      injection of a CCK analogue, caerulein, in male Sprague-Dawley rats. Exploratory
      activities were measured with an automated photobeam activity system and compared
      among different treatment groups. To confirm the inflammation, the pancreas was
      weighed and compared histologically with those taken from naive rats. Exploratory
      activity changed significantly in rats with experimental pancreatitis (i.e.,
      rearing events, rearing time, active time, distance traveled, and total activity
      all were decreased; whereas resting time was increased). The inflamed pancreatic
      tissues were edematous, with moderate to marked acinar atrophy and inflammatory
      infiltrate. Intrathecal administration (at the T7-T9 spinal levels) of an NMDA
      receptor antagonist (D-AP5, 1 microg) or a selective PKC inhibitor (GF109203X,
      0.15 microg) significantly reversed the changes in exploratory activity when
      compared with the vehicle-treated group of rats with experimental pancreatitis.
      Our results demonstrate that pancreatitis pain is the result of central pain
      processes that play a role in the amplification of responses to peripheral
      visceral input through NMDA receptor activation and PKC phosphorylation signaling
      pathways.

PMID- 14724054
TI  - Stimulus properties of the "atypical" antipsychotic zotepine in rats: comparisons
      with clozapine and quetiapine.
AB  - The stimulus properties of the "atypical" antipsychotic zotepine were assessed in
      three studies in rats. In Study 1, the ability of zotepine to generalise to
      clozapine was studied. Two groups of rats were trained to discriminate clozapine
      at 2 and 5 mg/kg. Clozapine induced full generalisation in both groups, with the
      generalisation curves shifted significantly to the left in the low dose group. In
      generalisation tests clozapine did not suppress responding. Zotepine induced dose
      related generalisation in both groups, with full generalisation in the low dose
      group and 50% maximal generalisation in the high dose group at the highest dose
      that could be tested. In contrast to clozapine, zotepine induced substantial (50%
      or more) substitution for clozapine only at doses which suppressed responding. In
      Study 2 zotepine was investigated in rats trained to discriminate quetiapine (10
      mg/kg). Quetiapine induced full generalisation and zotepine only induced 54%
      generalisation at the highest dose that could be tested. Generalisation was
      accompanied by response suppression induced by both quetiapine and zotepine. In
      Study 3 an attempt was made to train a zotepine discrimination (1 mg/kg increased
      to 2 mg/kg). Even after 150 training sessions it proved impossible to obtain
      reliable discriminative responding with zotepine. These data suggest that: (i)
      The actions of zotepine in discrimination assays are similar to, but not
      identical with, those of clozapine and quetiapine; (ii) The differences among the
      actions of clozapine, quetiapine and zotepine may be related to either the unique
      ability of zotepine to block noradrenaline (NA) uptake, or to its more marked
      affinity for D(2) receptors; (iii) The finding that zotepine only mimicked
      quetiapine up to a level of 54% was unexpected, since quetiapine and clozapine
      generalise reciprocally and zotepine generalised fully to (low dose) clozapine.
      This finding may also be related either to zotepine's ability to inhibit NA
      uptake or its relatively high D(2) affinity; (iv) Although zotepine clearly
      possesses discriminative properties, it is not possible to train it as a reliable
      stimulus, in contrast to clozapine and quetiapine. This may be due to its more
      marked D(2) receptor affinity. Collectively, these data demonstrate both
      similarities and differences between zotepine and other novel atypical
      antipsychotics in drug discrimination assays.

PMID- 14724055
TI  - Methylene blue improves brain oxidative metabolism and memory retention in rats.
AB  - Methylene blue (MB) increases mitochondrial oxygen consumption and restores
      memory retention in rats metabolically impaired by inhibition of cytochrome c
      oxidase. This study tested two related hypotheses using biochemical and
      behavioral techniques: (1) that low-level MB would enhance brain cytochrome c
      oxidation, as tested in vitro in brain homogenates and after in vivo
      administration to rats and (2) that corresponding low-dose MB would enhance
      spatial memory retention in normal rats, as tested 24 h after rats were trained
      in a baited holeboard maze for 5 days with daily MB posttraining injections. The
      biochemical in vitro studies showed an increased rate of brain cytochrome c
      oxidation with the low but not the high MB concentrations tested. The in vivo
      administration studies showed that the corresponding MB low dose (1 mg/kg)
      increased brain cytochrome c oxidation 24 h after intraperitoneal injection, but
      not after 1 or 2 h postinjection. In the behavioral studies, spatial memory
      retention in probe trials (percentage of visits to training-baited holes compared
      to total visits) was significantly better for MB-treated than saline control
      groups (66% vs. 31%). Together the findings suggest that low-dose MB enhances
      spatial memory retention in normal rats by increasing brain cytochrome c oxidase
      activity.

PMID- 14724056
TI  - Intrahippocampal administration of the alpha-keto acids accumulating in maple
      syrup urine disease provokes learning deficits in rats.
AB  - Learning disability is a common feature of patients affected by maple syrup urine
      disease (MSUD). However, the pathomechanisms underlying learning deficit in this
      disorder are poorly known. In the present study, we investigated the effect of
      acute administration of the alpha-keto acids accumulating in MSUD into the
      hippocampus on the behavior of rats in the open field and in the inhibitory
      avoidance tasks. Adult male Wistar rats received intrahippocampal injections of
      alpha-ketoisocaproic acid (KIC, 8 micromol), alpha-ketoisovaleric acid (KIV, 5
      micromol), alpha-keto-beta-methylvaleric acid (KMV, 5 micromol), or NaCl (8
      micromol) (controls) immediately after or 10 min before training. Testing session
      was performed 24 h later. Posttraining administration of the keto acids had no
      effect on learning in the open-field task. In contrast, pretraining
      administration of KIV and KMV impaired habituation in the open field. Similarly,
      pretraining administration of KIC, KIV, and KMV affected rat performance in the
      inhibitory avoidance task, suggesting disruption of acquisition. The results
      indicate that the alpha-keto acids accumulating in MSUD induce learning deficits
      in aversive and nonaversive tasks. We therefore suggest that these findings may
      be related to the psychomotor delay/mental retardation observed in MSUD, and may
      indicate the contribution of increased brain concentrations of these organic
      acids to the pathophysiology of the neurological dysfunction of MSUD patients.

PMID- 14724058
TI  - The German Center for Research on Aging at the University of Heidelberg: an
      interdisciplinary approach.
AB  - In September 1995, the German Center for Research on Aging at the University of
      Heidelberg had been founded to become a leading national center of excellence
      with a clear interdisciplinary scope of ageing research activities. So far, three
      departments have been built up successively: the Department of Social and
      Environmental Gerontology (established in 1997, chair: Prof. Hans-Werner Wahl),
      the Department of Adult Development (established in 1998, provisional chair:
      Prof. Andreas Kruse), and the Department of Epidemiology (established in 2000,
      chair: Prof. Hermann Brenner). As one of the next steps, the disciplinary
      spectrum of the Center will be complemented by setting up several junior research
      groups in molecular ageing research. Within the few years of its existence, the
      Center has set up multiple large-scale, extramurally funded cross-sectional, case
      control and longitudinal studies. These studies provide a unique common basis for
      interdisciplinary collaboration both within the Center and with the Center's
      numerous national and international research partners.

PMID- 14724059
TI  - Possible role of alteration of aldehyde's scavenger enzymes during aging.
AB  - Apoptosis in tissues is induced by different kind of signals including endogenous
      aldehydes, such as 4-hydroxy-2, 3-nonenal. The accumulation rate of aldehydes in
      the cell is affected by conditions of oxidative stress. In the cell, aldehydes
      can be metabolized by various isoforms of aldehyde dehydrogenase, aldehyde
      reductase, and glutathione-S-transferase. There is evidence suggesting that the
      catalytic properties of these enzymes change during ontogenesis, and that aging
      is accompanied by their reduced activities. These functional changes may
      contribute substantially to the alteration in the organism sensitivity to
      damaging action of stress factors during aging, to age-related modulation of the
      action of endogenous aldehydes as a signal for apoptosis, and finally, to the
      origin of diseases associated with aging. In this context, the stimulation of
      enzymes' expression, and the activation of the catalytic properties of enzymes
      responsible for catabolism of endogenous aldehydes could become a perspective
      direction in increasing the organism resistance to the action of damaging factors
      during aging.

PMID- 14724060
TI  - The contribution of reactive oxygen species to sarcopenia and muscle ageing.
AB  - Ageing is a complex process that in muscle in usually associated with a decrease
      in mass, strength, and velocity of contraction. One of the most striking effects
      of ageing on muscle is known as sarcopenia, a process that is the result of many
      cellular changes, such as a reduction in the number of motor units coupled with
      an increase in motor unit size, progressive denervation, decreased synthesis of
      myofibrillar components, atrophy due to disuse, accumulation of connective
      tissue, etc. It has been suggested that sarcopenia may be triggered by reactive
      oxygen species (ROS) that have accumulated throughout one's lifetime. ROS, which
      are generated by the addition of a single electron to the oxygen molecule, are
      formed in all tissues including muscle fibres and, especially, in the
      mitochondrial respiratory chain. Such reactive elements are usually quite harmful
      and result in oxidative stress that can damage other cellular components such as
      DNA, proteins, lipids, etc. resulting in further damage to the cells and tissues.
      As a consequence, the intra and intercellular membranes of the muscle fibers, in
      particular those of the Sarcoplasmic reticulum, may be modified and the Ca(2+)
      transport mechanism altered. During the ageing process ROS production may
      drastically increase because of an altered function of the respiratory chain and
      an insufficient functioning of the antioxidant cellular defences. How such an
      oxidative insult plays a role in the age-related decrease of muscle performance
      and mass has yet to be defined. What does have a clear role in the progression of
      sarcopenia is the significant reduction of the regenerative potential of muscle
      fibres. This reduction is due to a reduced pool of satellite cells that are
      usually recruited to replace damaged fibres and promote their regeneration.
      Exercise as a method to prevent or at least delay sarcopenia has been discussed
      in many scientific reports. While on the one hand, it seems clear that exercise
      is effective in reducing the loss of muscle mass, on the other it appears that
      physical activity increases both the mechanical damage and the accumulation of
      free radicals as a result of an increase in the aerobic metabolism of the muscles
      involved.

PMID- 14724061
TI  - Demographic heterogeneity explains age-specific patterns of genetic variance in
      mortality rates.
AB  - The genetic variance of mortality rates in Drosophila melanogaster increases with
      age early in life, but declines at intermediate ages. A simulation study was done
      in order to evaluate two competing explanations for this age-specific pattern:
      (1) demographic heterogeneity, and (2) binomial sampling effects. The pattern can
      be explained by demographic heterogeneity among and within genotypes. In
      contrast, binomial sampling variance is not sufficient to explain this age
      specific pattern of genetic variance in mortality rates. A previous publication
      that rejected the 'heterogeneity explanation' in favor of binomial sampling is
      shown to be mistaken.

PMID- 14724062
TI  - Leydig cell gene expression: effects of age and caloric restriction.
AB  - In mammals, the concentration of testosterone in blood serum typically becomes
      reduced with aging. We have shown that, in rats, this results from reduced
      testosterone production by individual Leydig cells. To gain an understanding of
      the mechanisms by which Leydig cell steroidogenic function changes with aging, we
      compared the gene expression profiles in Leydig cells isolated from young and old
      Brown Norway rats, focusing on possible changes in genes involved in, or
      associated with, steroidogenesis. We also explored the effects of caloric
      restriction, an intervention shown to delay or inhibit age-associated pathologic
      and biologic changes in a number of systems and organisms, on the expression of
      these genes. Of the total of 1176 genes arrayed on each of the five membranes per
      group that we used, about 500 (45%) were detectable in Leydig cells isolated from
      young and old rat testes, with the same genes detectable in cells from both ages.
      An ANOVA model was applied to statistically analyze the 500 detectable genes in
      the four treatment groups. The primary criterion by which interesting genes were
      selected was a P value of </=0.05. With aging, a large number of genes were seen
      with fold changes of >1.5. However, when P</=0.05 was used as the selection
      criterion, only 45 genes were seen to change significantly with age. Most, but
      not all, of these genes also had fold changes of >1.5. Among the 500 genes, 17
      were found to decrease in expression with aging, the most prominent among which
      were genes involved in steroidogenesis and stress response/free radical
      scavenging. Long-term caloric restriction had little effect on the 45 genes
      altered by age. In contrast to the effects of caloric restriction as seen in many
      other cell types and systems, the vast majority (44/45) of the Leydig cell genes
      that changed with age were not 'rescued' by this intervention.

PMID- 14724063
TI  - Changes of prolactin regulatory mechanisms in aging: 24-h rhythms of serum
      prolactin and median eminence and adenohypophysial concentration of dopamine,
      serotonin, (gamma-aminobutyric acid, taurine and somatostatin in young and aged
      rats.
AB  - Twenty-four hour rhythmicity of serum prolactin and median eminence and anterior
      pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid
      (GABA), taurine and somatostatin were examined in 2 months-old and 18-20 months
      old Wistar male rats. The concentration of prolactin was higher in aged rats,
      with peaks in both groups of rats at the early phase of the activity span. Median
      eminence DA content of young rats attained its maximum at the middle of rest span
      and decreased as prolactin levels augmented while the lowest values of
      adenohypophysial DA were observed at the time of prolactin peak. DA rhythmicity
      disappeared in aged rats. GABA content of median eminence and adenohypophysis was
      lower in aged rats, with maximal values of median eminence GABA at light-dark
      transition in young rats and at the second half of activity span in aged rats.
      Serum prolactin correlated positively with median eminence GABA in young rats and
      negatively with pituitary GABA in young and aged rats. Median eminence
      somatostatin peaked at the beginning of the activity phase (young rats) or at the
      end of the rest phase (aged rats). Prolactin levels and somatostatin content
      correlated significantly in young rats only. Median eminence and pituitary 5HT
      and taurine content did not change with age. The results indicate disruption of
      prolactin regulatory mechanisms with aging in rats.

PMID- 14724064
TI  - The effect of aging on the immunohistochemistry of apolipoprotein E in the liver.
AB  - Apolipoprotein E (apoE) is involved in hepatic disposition of chylomicron
      remnants, which is impaired in old age. Isoforms of apoE have been implicated in
      age-related diseases and possibly the aging process itself. Because the effects
      of old age on expression and distribution of apoE in the liver have not been
      reported, we studied the effect of old age on the immunohistochemistry of apoE in
      the livers of humans and the non-human primate, Papio hamadryas. Overall, old age
      was not associated with marked changes in the expression of apoE between adult
      (48+/-19 years) and old (82+/-5 years) humans. However, there was a change in the
      distribution of apoE staining. The livers of older humans displayed increased
      hepatocyte cytoplasmic staining and reduced peri-sinusoidal staining. Similar
      trends were noted in the livers from the baboons. Such findings are suggestive of
      altered apoE recycling in old age and have implications for age-related
      dyslipidaemia.

PMID- 14724065
TI  - Study of factors influencing the decreased HDL associated PON1 activity with
      aging.
AB  - Paraoxonase (PON1) is principally complexed to HDL and is responsible, at least
      in part, for its antioxidant properties. PON1 activity decreases in several
      pathologies associated with atherosclerosis. The aim of this study was to
      investigate the PON1 activity and factors influencing its activity as a function
      of age. One hundred and twenty nine healthy subjects aged between 22 and 89 years
      were recruited for the study. We found that serum PON1 activity significantly
      decreased with age (r=-0.38, p<0.0001) while its arylesterase activity as well as
      its concentration in the serum did not change significantly. HDL concentrations
      remained unchanged with age, however, Apo A1 concentration showed a slight
      negative but significant correlation with age (r=-0.19, p<0.027). Moreover, the
      total cholesterol concentration was positively and significantly correlated with
      age (r=0.40, p<0.001). Thus, our results suggest that the decrease in PON1
      activity cannot be explained by the decrease in Apo A1 concentrations with age.
      HDL from elderly subjects was more susceptible to oxidation than HDL from young
      subjects measured by higher lipid peroxidation rate. Thus, the decrease in PON1
      activity may contribute to this increased susceptibility of HDL to oxidation with
      aging. Altogether our results suggest that the decrease in PON1 activity may be
      related to the development of oxidative stress conditions with aging and the
      increased HDL susceptibility to oxidation in elderly subjects.

PMID- 14724066
TI  - Low molecular weight antioxidants released from the skin's epidermal layers: an
      age dependent phenomenon in the rat.
AB  - Skin is one of the tissues most exposed to oxidative stress both from endogenous
      and exogenous sources. Therefore, it can be speculated that skin possesses an
      extremely efficient antioxidant defense mechanism, particularly in its epidermal
      layers. The present study shows that human and rat skins possess different and
      unique reducing antioxidant profiles. These reducing antioxidants can be washed
      out into the surrounding environment. Non-invasive measurements indicated that
      skin releases low molecular weight antioxidants (LMWA) from its epidermal layers.
      Cyclic voltammetry measurements have shown that rat skin releases three major
      groups of reducing antioxidants at peak potentials of 476 and 889 and 1044 mV
      while human skin releases two major groups at peak potentials of 779 and 1068 mV.
      In rat, the overall concentrations of the LMWA secreted decreased significantly
      with age. The major components of the LMWA composing the first anodic wave in
      rats were identified as uric acid and ascorbic acid. Uric acid and other as yet
      uncharacterized LMWA, but not ascorbic acid, were released in human skin.
      Differences in the ability to release high levels of uric acid among species were
      well correlated with their metabolic rates. It is suggested that in rat the
      released LMWA may serve as a possible marker for aging of the skin.

PMID- 14724067
TI  - Aging of innate immunity: functional comparisons of NK/LAK cells obtained from
      bulk cultures of young and aged mouse spleen cells in high concentrations of
      interleukin-2.
AB  - The technique of bulk cultivation of aged mouse spleen cells in high
      concentration of IL-2 was employed to obtain NK/LAK cells in sufficient number
      and enrichment for studies on the effects of aging on their functions. The yield
      and enrichment were equivalent to that of young mouse spleen cells. The aged and
      young mouse NK/LAK cells were equivalent also in their functional competence to
      proliferate, kill target cells and produce IFNgamma; i.e. they did not display
      age-associated defects typical of freshly-isolated NK/LAK cells. In two respects,
      however, the NK/LAK cells derived from aged mouse spleen were altered: (a) in the
      efficiency of nuclear translocation of transcription factors STAT 5A and 5B, and
      (b) in the deficiency in production of mRNA transcripts representing several
      chemokines. We recommend caution in the use of bulk cultivation in IL-2 to obtain
      NK/LAK cells for studies on aging. However, it does appear from this study that
      aging may severely affect chemokine production, at least in the case of NK/LAK
      cells.

PMID- 14724068
TI  - Heat shock response by EBV-immortalized B-lymphocytes from centenarians and
      control subjects: a model to study the relevance of stress response in longevity.
AB  - 'Successful aging', i.e. the ability to attain old age in relatively good health,
      is believed to be related to the capability to cope with different environmental
      stresses. Independently of their specific differentiation, all body cells respond
      to hyperthermia and other stresses with the production of Heat Shock Proteins
      (HSPs) that play an important role in cell survival. We investigated the heat
      shock response in B-lymphoid cell lines from 44 centenarians and 23 younger
      subjects, by studying both HSP70 synthesis and cell survival after hyperthermic
      treatment. Interestingly, no significant difference could be found between the
      two age groups as far as HSP70 synthesis was concerned; moreover, cell lines from
      centenarians appeared to be less prone to heat-induced apoptosis than lines from
      younger controls. These results, which are in contrast with previous findings
      showing an age-related decrease of the HSP70 synthesis and of hyperthermic
      response, corroborate the above mentioned hypothesis that the biological success
      of centenarians is due to the preservation of the capability to cope with
      stresses. An A/C polymorphism identified in the promoter region of HSP70-1 gene
      had been previously shown to affect the probability to attain longevity in
      females. To investigate if this effect was related to any influence of this
      polymorphism on HSP70 protein synthesis the correlation between A/C polymorphism
      and protein synthesis was investigated. We found that cells from AA centenarian
      females displayed a lower synthesis of HSP70.

PMID- 14724069
TI  - Aging-related alterations in the contractile responses to acetylcholine,
      muscarinic cholinoceptors and cholinesterase activities in jejunum and colon of
      the male Fischer 344 rats.
AB  - In an attempt to examine whether the muscarinic receptor-activated intestinal
      function is altered by aging, we studied the changes in (1) contractile responses
      to acetylcholine (Ach), (2) muscarinic cholinoceptors and (3) cholinesterase
      (ChE) activities, in jejunum and colon of the young (2-3 months) and aged (24-28
      months) Fischer 344 rats. In the physiological contraction experiments of jejunum
      and colon, Ach concentration-dependently increased the force of contraction, and
      the contractile responses to Ach were not affected by aging. In addition, the
      true- and pseudo-ChE activities were not significantly changed by aging. The Ach
      induced contraction was competitively inhibited by muscarinic M3-selective
      antagonist hexahydro-sila-difenidolhydrochloride p-fluoroanalog (p-F-HHSiD),
      suggesting that the contractile responses in the rat jejunum and colon were
      mediated through M3-cholinoceptor. Age-related changes in muscarinic
      cholinoceptors of jejunum and colon were determined with the use of specific
      muscarinic radioligand [3H]-quinuclidinylbenzilate (QNB). The [3H]QNB saturation
      binding experiments revealed that the maximal binding (B(max)) was increased only
      in aged jejunum without changes in K(D) values. These results suggest that aging
      may not attenuate the Ach-induced intestinal contraction via muscarinic M3
      receptor, although the expression of muscarinic cholinoceptor is differentially
      modulated in jejunum and colon.

PMID- 14724070
TI  - Chromogranin peptides in Alzheimer's disease.
AB  - Synaptic disturbances may play a key role in the pathophysiology of Alzheimer's
      disease. To characterize differential synaptic alterations in the brains of
      Alzheimer patients, chromogranin A, chromogranin B and secretoneurin were applied
      as soluble constituents for large dense core vesicles, synaptophysin as a vesicle
      membrane marker and calbindin as a cytosolic protein. In controls, chromogranin B
      and secretogranin are largely co-contained in interneurons, whereas chromogranin
      A is mostly found in pyramidal neurons. In Alzheimer's disease, about 30% of beta
      amyloid plaques co-labelled with chromogranin A, 20% with secretoneurin and 15%
      with chromogranin B. Less than 5% of beta-amyloid plaques contained synaptophysin
      or calbindin, respectively. Semiquantitative immunohistochemistry revealed a
      significant loss for chromogranin B- and secretoneurin-like immunoreactivity in
      the dorsolateral, the entorhinal, and orbitofrontal cortex. Chromogranin A
      displayed more complex changes. It was the only chromogranin peptide to be
      expressed in glial fibrillary acidic protein containing cells. About 40% of
      chromogranin A immunopositive plaques and extracellular deposits were surrounded
      and pervaded by activated microglia. The present study demonstrates a loss of
      presynaptic proteins involved in distinct steps of exocytosis. An imbalanced
      availability of chromogranins may be responsible for impaired neurotransmission
      and a reduced functioning of dense core vesicles. Chromogranin A is likely to be
      a mediator between neuronal, glial and inflammatory mechanisms found in Alzheimer
      disease.

PMID- 14724071
TI  - Early atherogenesis in senescence-accelerated mice.
AB  - We studied atheromatous lesion formation in an animal model of accelerated
      ageing. The senescence-accelerated prone mouse (SAM-P) has a reduced life-span
      and exhibits clinical features characteristic of human ageing. Our aim was to
      establish whether these mice are more susceptible to atherosclerosis than a
      related strain, senescence-accelerated resistant mice (SAM-R), which age
      normally. We fed a Western-type diet to 14 SAM-P/8 and 14 SAM-R/1 mice for 17
      weeks, starting at 28 weeks of age, measuring their serum lipid profiles before
      and after this diet. We stained aortic root cryostat cross-sections with Oil red
      O, and assessed lipid deposition morphometrically. We used immunohistochemistry
      to detect macrophages in the aortic roots. We found that despite showing similar
      alterations in lipid profile, SAM-P/8 mice developed more prevalent and extensive
      fatty lesions than SAM-R/1 mice. Furthermore, the lipid lesions in SAM-P/8 mice
      showed a greater frequency of invasion by macrophages. We conclude that mice,
      which age at an accelerated rate, are more prone to early atherogenesis than mice
      which age normally. We suggest that this increased susceptibility may result from
      abnormalities in the oxidative status and cellular replicative capacity of these
      mice.

PMID- 14724072
TI  - Age-related changes in matrix metalloproteinase-9 regulation in cultured mouse
      aortic smooth muscle cells.
AB  - We previously reported that aortic smooth muscle cells (SMC) from aged mice have
      an age-related decline in proliferative capacity compared with those derived from
      young mice. Here we investigated matrix metalloproteinase-9 (MMP-9) regulation in
      both young and aged SMC. Zymography, immunoblot, and northern blot analysis
      showed that MMP-9 expression is significantly reduced in response to tumor
      necrosis factor-alpha stimulation with increasing in vitro age. Mutational
      analysis, gel shift assays and supershift assays demonstrated that the lower MMP
      9 expression in aged SMC is associated with lower activities of NF-kappaB and AP
      1. Since mitogen-activated protein kinase ERK1/2 induce MMP-9 expression, we
      examined whether U0126, an ERK1/2 inhibitor, influenced MMP-9 expression in aged
      SMC. Treatment with U0126 successfully inhibited MMP-9 expression in both young
      and aged SMC. Finally, to analyze the causal relationship between replicative
      senescence and MMP-9 expression, we stably overexpressed the MMP-9 gene in aged
      SMC and we showed no alteration of the proliferative capacity of the transduced
      cells. Taken together, these results suggest that down-regulation of MMP-9
      expression in SMC may play a role in vascular remodeling during in vitro aging.

PMID- 14724073
TI  - Age-related differences in metabolic adaptations following resistance training in
      women.
AB  - The purpose of this study was to determine whether aging alters changes in
      resting metabolic rate, body composition and insulin sensitivity in response to
      resistance training (RT) in women. The impact of a 6-month controlled RT program
      on fat-free mass (FFM), resting energy expenditure (REE), and glucose disposal
      was examined in 19 younger (27.8+/-3.5 yr; range 18-35) and 12 older (66.6+/-4.9
      yr, range 55-70) non-obese caucasian women. For younger women, the RT program
      increased body weight (59.1+/-6.2 to 60.8+/-6.1 kg, p<0.05) due to an increase in
      FFM (39.2+/-3.7-40.4+/-3.2 kg, p<0.05). REE increased from 1379+/-114 to 1451+/
      140 kcal day(-1), p<0.0001), and glucose disposal (from 364.1+/-91.1 to 402.1+/
      87.8 mg min(-1), p<0.05). Neither fat mass nor VO2max changed significantly. On
      the other hand, older women lost fat mass (24.0+/-4.6-23.2+/-5.4 kg, p<0.05) and
      tended to gain FFM (from 37.3+/-4.0-38.0+/-4.3 kg, +1.9%; p=0.057), whereas no
      change occurred in body weight, REE, VO(2)max or glucose disposal. Thus, younger
      women showed greater metabolic changes in body composition, REE and insulin
      sensitivity in response to RT than older women. These results suggest an age
      related alteration in metabolic changes in response to a 6-month RT program in
      previously untrained women.

PMID- 14724074
TI  - Effects of UV-A irradiation on lens morphology and optics.
AB  - Epidemiological studies have indicated that ultraviolet radiation (UVR) is one of
      the main factors leading to senile cataract formation. We investigated
      morphological changes in the eye lens caused by UVR-A. Twenty three pairs of
      lenses obtained from 23 one-year-old calves were used for this study. For each
      pair, one lens was exposed to 44 J/m(2) UVR in the 365 nm wavelength region while
      the contralateral lens was not exposed and served as a control. The lenses were
      placed in specially designed organ culture containers for pre-incubation. Lenses
      were exposed to UVR after one day in culture. After irradiation, lens optical
      quality was monitored throughout additional 15 days of the culture period and
      lenses were taken for morphological analysis by scanning electron microscopy.
      Damage to lens optical quality was evident as early as day 8 after the
      irradiation and increased with time in culture. We found irregularity of fiber
      morphology in lenses exposed to UV-A irradiation (but not in control lenses),
      similar to that reported previously for aged lenses. At the end of the culture
      period (day 16), lens fiber membranes also showed holes in fiber membranes. We
      conclude that UVR-A caused damage to cell membranes of the lens and alterations
      in lens optics, which may subsequently lead to senile cataract formation.

PMID- 14724075
TI  - Potential role of high serum leptin concentration in age-related decrease of
      fatty acid synthase gene expression in rat white adipose tissue.
AB  - Ageing in rats is associated with significant reduction of lipogenic enzymes
      genes expression and the rate of fatty acids synthesis in white adipose tissue.
      Since resistance to insulin and/or triiodothyronine is not directly related to
      reduction in lipogenic enzymes activity in white adipose tissue of old rats, we
      have proposed recently that the age-related increase in leptin gene expression
      and high serum leptin concentration could, at least partly, account for the down
      regulation of lipogenic enzymes gene expression. To test this hypothesis, in this
      paper we experimentally (by single intraperitoneal injection of recombinant
      leptin) increased plasma leptin concentration in young rats to the level observed
      in old animals, and we examined its effect on fatty acids synthase (FAS) gene
      expression in white adipose tissue. The results presented in this paper indicate
      that leptin administration to young rats, in amount that cause the increase in
      serum leptin concentration to that found in old rats, significantly decreased the
      white adipose tissue FAS gene expression. We propose, therefore, that leptin
      could play a causative role in the down-regulation of lipogenic enzyme gene
      expression observed with ageing.

PMID- 14724077
TI  - Informed consent, the parturient, and obstetric anesthesia.

PMID- 14724078
TI  - An analysis of reintubations from a quality assurance database of 152,000 cases.
AB  - STUDY OBJECTIVE: To determine if the majority of reintubations, a potentially
      preventable adverse event, were predominantly due to residual muscle relaxant
      effects, we analyzed our quality assurance database to identify the causes of
      reintubation. DESIGN: Retrospective study. SETTING: University of Michigan
      Department of Anesthesiology Quality Assurance (QA) database. MEASUREMENTS: We
      analyzed QA records from 152,939 anesthetic cases performed from 1994 to 1999 at
      our institution. Of these cases, 107,317 were performed with a general
      anesthetic. The medical record of each patient requiring reintubation was
      obtained and reviewed to determine the cause of the reintubation. RESULTS: A
      total of 191 reintubation events were identified. One hundred twelve of the 191
      (59%) reintubations were due to respiratory problems; 11 of the 191 (6%)
      reintubations were due to complications of neuromuscular blocking drug use. Other
      causes were unintentional extubation, surgical complication, endotracheal tube
      problems, and cardiac problems. One hundred five reintubations (105/191, 55%)
      occurred in the operating room and 86 (86/191, 45%) occurred in the
      postanesthesia care unit. CONCLUSION: Respiratory complications were the most
      common cause of reintubation in the perioperative period. Complications related
      to the neuromuscular blocking drugs were the fourth most common cause of
      reintubation. More reintubations occurred in the operating room than the
      postanesthesia care unit. Muscle relaxant effect and opioid effect are rare
      causes of respiratory failure in the anesthetized patient in the immediate
      postoperative period.

PMID- 14724079
TI  - Brachial plexus injury following subclavian vein catheterization: a case report.
AB  - Subclavian vein cannulation may be complicated by lesions of the peripheral
      nervous system, such as injury to the recurrent laryngeal nerve, phrenic nerve,
      and brachial plexus. We describe a case of lesion of the upper trunk of the
      brachial plexus during multiple attempts at subclavian vein catheterization. This
      type of complication, ascribed to erroneous application of procedures or
      anatomical variations, may be minimized by abstaining from multiple attempts at
      venipuncture.

PMID- 14724080
TI  - Ethical aspects of informed consent in obstetric anesthesia--new challenges and
      solutions.
AB  - Informed consent is a cornerstone and routine component of the ethical practice
      of modern medicine. Its full theoretical application to specific clinical
      situations, however, presents a number of ethical dilemmas for health care
      providers. Obstetric anesthesia, in particular, presents many unique challenges
      to the process of informed consent. In this review, the ethical background to the
      doctrine of informed consent within the context of "principlism" is explored and
      critiqued. The application of principlism to actual clinical situations, the
      limitations of principlism in the peculiarities of the patient-physician
      encounter, as well as possible alternative models of ethical discourse is
      discussed. The process of informed consent can be broken down into seven
      elements: Threshold elements or preconditions, which include 1) decision-making
      capacity or competency of the patient, 2) freedom or voluntariness in decision
      making, including absence of over-riding legal or state interests; informational
      elements, including 3) adequate disclosure of material information, 4)
      recommendation, and 5) an understanding of the above; consent elements, which
      include 6) decision by the patient in favor of a plan and 7) authorization of
      that plan. Each of these elements is discussed in turn, and their implications,
      especially for the anesthesiologist and the obstetric patient, are addressed.

PMID- 14724082
TI  - Preparation and characterization of monoclonal antibodies against S1 domain at N
      terminal residues 249 to 667 of SARS-associated coronavirus S1 protein.
AB  - OBJECTIVE: To prepare and characterize monoclonal antibodies (mAbs) against S1
      protein of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS
      CoV). METHODS: 6-His-tagged recombinant fragment at N-terminal residues 249 to
      667 of SARS-CoV S1 protein including S-protein receptor-binding domain was
      expressed in E.coli. The immunogenicity of this S1 domain was identified and used
      to immunize BALB/c mice for the production of hybridomas. The identification of
      the mAbs against this S1 domain was performed using indirect enzyme-linked
      immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA) and Western
      blotting, respectively. RESULTS: Three hybridomas producing mAbs specific to the
      S1 domain was obtained, with a relative molecular mass of 48,500. None of the 3
      mAbs were reactive with human coronaviruses 229E and OC43. Two of the mAbs were
      IgG2a isotype, and the other was IgG1. CONCLUSIONS: This is the first report of
      mAbs produced against S-protein receptor-binding domain of SARS-CoV. The 3 S1
      specific mAbs may be useful for further study of the function of the S protein
      and for diagnosis of SARS-CoV infection.

PMID- 14724083
TI  - In situ expression of thyrotropin receptor in the extraocular muscles of patients
      with thyroid-associated ophthalmopathy.
AB  - OBJECTIVE: To investigate the expression of thyrotropin receptor (TSHR) in the
      extraocular muscles (EOM) of the eyes of patients with thyroid-associated
      ophthalmopathy (TAO). METHODS: EOM specimens were obtained from 12 patients with
      severe TAO and 10 healthy subjects within 1 hour after accidental death and the
      paraffin-embedded sections were observed by streptavidin-peroxidase (SP)
      immunohistochemical methods. RESULT: The expression of TSHR was observed in the
      perimysium, cytomembrane and cytoplasm in 10 of the 12 TAO specimens, accounting
      for a TSHR expression rate of 83.3% in the EOM of TAO patients. No TSHR protein
      was found in the healthy subjects. CONCLUSION: High TSHR expression in the EOM of
      TAO patients indicates that as a common antigen between the orbit and thyroid,
      TSHR play a key role in the pathogenesis of TAO.

PMID- 14724084
TI  - [Using chamber technique for studying the permeability of dexamethasone sodium
      phosphate liposome through rabbit colon mucosa in vitro].
AB  - OBJECTIVE: To investigate the features of liposome-mediated drug permeability
      through the colon mucosa in vitro. METHODS: Dexamethasone sodium phosphate
      liposome (DSP) was prepared using orthogonal design. With in vitro Ussing chamber
      experiment, the accumulated amount of DSP permeated through rabbit colon mucosa
      into the receptor chamber and the distribution amount in the colon were
      determined at different time points during the experiment. RESULTS: Compared with
      the prepared DSP solution, DSP liposome decreased the permeated amount of DSP
      through rabbit colon mucosa. The apparent permeability coefficient (Papp, x10(
      6), cm/s1) of the DSP was 31.95+/-7.65, significantly lower than that of DSP
      solution (88.61+/-18.61). On the other hand, the distribution amount of DSP
      liposome in the colon mucosa was significantly higher than that of the DSP
      solution both at 120 and 300 min. CONCLUSIONS: DSP liposome dosage form may
      induce less toxicity with better therapeutic effect in the treatment of colitis,
      which is worthy of further exploitation.

PMID- 14724085
TI  - [Preparation of a novel targeted MR contrast agent Gd-DTPA-streptavidin and
      exploration of its reaction conditions].
AB  - OBJECTIVE: To explore the optimal reaction condition of DTPA-coupled streptavidin
      labeled with gadolinium ion. METHODS: The number streptavidin-coupled of
      gadolinium ions and maximum biotin-binding capacity of Gd-DTPA-SA complex were
      analyzed at different DTPA-to-SA molar ratios (1000, 500, 200, 100) and in buffer
      solutions of different pH values (pH 5, 6, 7, and 8, respectively). RESULTS: The
      number of streptavidin-coupled gadolinium ions increased with the pH value of the
      reaction system. When the DTPA-to-SA molar ratio was below 500, the number of
      gadolinium ions that SA-DTPA coupled increased with the DTPA-to-SA molar ratio,
      but tended to decrease when the ratio was 1,000. No significant difference in the
      maximum biotin-binding capacity of Gd-DTPA-SA complex was noted between the
      groups. CONCLUSIONS: The number of gadolinium ions that streptavidin coupled
      depends on the pH value of the reaction system and DTPA-to-SA molar ratio, but
      the maximum biotin-binding capacity of Gd-DTPA-SA complex is not affected by the
      reaction conditions.

PMID- 14724086
TI  - [Mathematical model of epidermal growth factor receptor-mediated lipid
      phosphatidylinositol(4,5)-bisphosphate hydrolyzation by phospholipase C-gamma1
      activity].
AB  - OBJECTIVE: To investigate the dynamic characteristics of lipid
      phosphatidylinositol (4,5)-bisphosphate (PIP(2)) in plasma membrane hydrolyzed by
      phospholipase C-gamma1 in epidermal growth factor receptor(EGFR)-mediated signal
      pathway. METHODS: A mathematical model based on the law of mass action was
      established with differential equations to simulate metabolizable pathway of
      PIP(2). RESULTS: Differential equations of the key product concentration during
      hydrolysis of PIP(2) were formulated, and the effects of the parameters on these
      hydrolyzed products analyzed. CONCLUSION: This mathematical model provides
      foundation for further investigation of the dynamic changes of biological
      characteristics and the relations between the key product concentrations in PIP2
      hydrolysis.

PMID- 14724087
TI  - [Conditions of contrast ultrasound that affect the proliferation of rat smooth
      muscle cells].
AB  - OBJECTIVE: To investigate the effect of an echo-contrast agent on the
      proliferation of rat smooth muscle cells under different ultrasound conditions.
      METHODS: The vascular smooth muscle cells of rats were cultured with echo
      contrast agent in 96-well plates, followed by exposure to ultrasound of different
      conditions. Trypan blue staining was performed 48 h later, and the proliferation
      of the cells observed by MTT assay. RESULTS: No cytotoxicity was found by trypan
      blue staining when the mechanical index of ultrasound was below 0.75. Compared
      with the control cells, the proliferation of the smooth muscle cells was
      decreased following the exposure as the mechanical index of ultrasound increased.
      The most obvious inhibition of cell proliferation was resulted when the
      microbubble concentration was 20% for a 60-second exposure. CONCLUSIONS: The
      inhibition of the vascular smooth muscle cell proliferation by echo-contrast
      agent destruction is correlated with the mechanical index of the ultrasound,
      concentration of the echo-contrast agent, and exposure time of ultrasound.

PMID- 14724088
TI  - [Analysis of the association between the quantity of insoluble particles in
      intravenously administered solution with adverse drug reactions].
AB  - OBJECTIVE: To investigate the possible association between adverse drug reactions
      and the quantity of insoluble particles in the intravenously administered drugs.
      METHODS: The solutions were prepared following the procedures in routine clinical
      practice, and the quantity of insoluble particles in these solutions were
      measured before and after the solutions went through the transfusion apparatus.
      RESULTS: The quantity of insoluble particles measured after the solutions passed
      through the transfusion apparatus was consistent with the standard documented in
      Chinese Pharmacopoeia. CONCLUSION: Adverse intravenous reactions occurring in our
      hospital has no association with excessive quantity of insoluble particles in the
      administered drugs.

PMID- 14724089
TI  - [In vitro study of formalin-fixed bone tissues for allogeneic bone grafting].
AB  - OBJECTIVE: To conduct an in vitro study to assess the preliminary possibility of
      using formalin-fixed, instead of fresh, human bone tissues for allografting.
      METHODS: Fresh cadaveric bone tissues were fixed by formalin for more than 6
      months and dissected into 5 mmx5 mmx5 mm pieces and 5 mmx5 mmx40 mm sticks,
      followed by chemical treatments to prepare the allograft bone materials. When
      alls treatments were completed, the bone grafts were centrifuged and their
      properties and cellular compatibility assessed in comparison with the currently
      used bone grafts clinically. RESULTS: The residual formaldehyde of the fixed
      allograft bone material was much below the controlled level and no significant
      differences were noted between the bone graft materials tested in regard to the
      chemical and mechanical properties and biocompatibility. CONCLUSION: This
      material we have prepared may meet the clinical demands for bone grafting, with
      good biocompatibility and less chance for infection by pathological agents.

PMID- 14724090
TI  - [General pharmacology of koumine parenteral solution].
AB  - OBJECTIVE: To determine the effect of koumine parenteral solution on the nervous,
      respiratory and cardiovascular systems of experimental animals. METHODS: Mouse
      spontaneous activities under the influence of the koumine injection were recorded
      with a photoelectric counter, and canine femoral artery pressure was determined
      by CYS-0.5 pressure transducer, respiratory curve described with TB-611 tension
      transducer and electrocardiogram (ECG) recorded with subcutaneous electrodes in
      the extremities after the injection. The above indices were automatically sampled
      and processed by multifunctional signal processor after being inputt to a
      computer. In this experiment, we observed the changes in the general behavior of
      the mice and their spontaneous activities within 15 min, along with the heart
      rate, maximum, minimum, and mean value of cardiac electric voltage, mean arterial
      pressure, respiratory rate and respiratory depth of the dogs before and at 10,
      20, 30, 60, 90, 120 min after koumine injection. RESULTS: Koumine injection
      significantly decreased mouse spontaneous activities in moderate and high-dose
      groups, but did not produce obvious effect on the respiratory system, mean
      arterial pressure, and maximum, minimum, and mean values of cardiac electric
      voltage in dogs. The heart rate of the dogs did not undergo obvious changes in
      response to the injection at a low dose, but median and high doses of the
      injection produced obvious effects. CONCLUSION: Koumine injection has definite
      sedative effect in mice, and does not affect the respiratory and cardiovascular
      systems of dogs with the exception of the heart rate.

PMID- 14724091
TI  - [Blocking with double- stranded RNA of the expression of Hes5 in rat bone marrow
      derived neural stem cells].
AB  - OBJECTIVE: To examine the efficiency of exogenous small double-stranded RNA
      (dsRNA) in knocking down the gene expression at the post-transcription level, and
      investigate the factors that may influence the transfection. METHOD: The bone
      marrow stromal cells of SD rat were separated and cultured in vitro, followed by
      induction of the cells to evolve into neural stem cells using special culture
      medium prepared by our laboratory. Synthetic dsRNA was then transferred into the
      cells at varied concentrations, and the results were analyzed by Western
      blotting. RESULTS: The concentrations ranging from 200 to 300 nmol/L were optimal
      for specifically blocking the expression of Hes5, whereas the suitable
      concentrations for the cell survival were between 50 and 200 nmol/L. CONCLUSION:
      dsRNA is capable of triggering RNA interference in neural stem cells, and at
      appropriate concentration, it may specifically and effectively knock down
      endogenous gene expression without sacrificing the viability of the cells.

PMID- 14724092
TI  - [Amplification and cloning of the N gene of SARS-associated coronavirus].
AB  - OBJECTIVE: To amplify and clone the N gene of severe acute respiratory syndrome
      associated coronavirus. METHOD: Using primer Premier 5.0 software, two pairs of
      nested PCR primers were designed to amplify the N gene. After purification, the
      amplified products were cloned into pMD18-T vectors, and the positive clones with
      the inserted fragments were identified by sequence analysis. RESULTS: The
      amplified products was about 1 375 bp in length, and sequence analysis
      demonstrated that the N gene fragments had been successfully inserted into pMD18
      T vectors. CONCLUSION: The successful amplification and cloning of N gene
      facilitates further investigation of the expression of the N protein and study of
      its structure and functions.

PMID- 14724093
TI  - [Effects of the lipid-lowering drugs on endothelial hyperplasia in inferior vena
      cava grafts in dogs].
AB  - OBJECTIVE: To investigate the effects of the lipid-lowering drugs in alleviating
      endothelial hyperplasia in the inferior vena cava (IVC) grafts in dogs. METHODS:
      The Dacron grafts seeded with autologous venous fragments were implanted into the
      IVC of 20 dogs, including 12 dogs receiving oral lipid-lowering drugs serving as
      the treatment group and the other 8 without medication as the control group. The
      levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-ch)
      and high-density lipoprotein cholesterol (HDL-ch) in the serum were measured
      regularly, and all the grafts harvested to measure the thickness of the
      endothelium. RESULTS: The total patency rate of the IVC were higher in the
      treatment group (75%) than in the control group (37.5%), and new endothelial
      lining was formed two weeks after the operation. Compared with the control group,
      the endothelial thickness of the grafts at the proximal (P<0.01), middle (P<0.05)
      and distal segments (P<0.05) of the IVC were all smaller in the treatment group,
      which also had lower serum LDL-ch and TC levels (both P<0.05) but with comparable
      HDL-ch levels (P>0.05). CONCLUSION: Administration of lipid-lowering drugs may
      reduce the level of serum LDL-ch and TC and the endothelial thickness of the
      grafts to improve the patency rate of the vessels.

PMID- 14724094
TI  - [Preparation of the microarray for detecting hepatitis D virus].
AB  - OBJECTIVE: To prepare the microarray for detection of hepatitis D virus (HDV).
      METHOD: Several pairs of specific PCR primers were designed according to the
      conserved region of HDV genome. The DNA microarray were prepared by blotting the
      PCR products onto the surface of glass slides with the use of robotics, and
      restriction display PCR (RD-PCR) was employed to label the samples. RESULT:
      Sequences analysis showed that the products of PCR amplification were the
      specific gene fragments of HDV. Hybridization signals on the gene chip
      demonstrated good specificity and sensitivity of the microarray for HDV
      detection. CONCLUSION: Microarray-based clinical HDV detection can be sensitive
      and effective.

PMID- 14724095
TI  - [DNA microarray for the detection of Yersinia pesits].
AB  - OBJECTIVE: To develop a DNA microarray technique for fast diagnosis of plague.
      METHODS: Restriction display polymerase chain reaction (RD-PCR) and hybridization
      with fluorescently labeled cy5 were employed for detecting the sample DNA of
      Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica.
      RESULTS: The prepared microarray is capable of distinguishing Yersinia pestis
      from Yersinia pseudotuberculosis and Yersinia enterocolitica in the same genus.
      CONCLUSION: The constructed DNA microarray is an effective diagnostic tool for
      the detection of Yersinia pestis.

PMID- 14724096
TI  - [Effects of recombinant human interleukin-10 on tumor necorsis factor-alpha
      induced adventitial fibroblast proliferation in vitro].
AB  - OBJECTIVE: To observe the effects of recombinant human interleukin-10 (rhIL-10)
      on adventitial fibroblast proliferation induced by tumor necrosis factor-alpha
      TNF-alpha in vitro. METHODS: In this controlled study, NIH/3T3 cells cultured in
      vitro were treated with TNF-alpha and recombinant human interleukin-10 (rhIL-10),
      respectively, and the cell proliferation was determined by non-radioactive
      MTS/PES assay. Cell cycle analysis was performed using flow cytometry. RESULTS:
      Compared with the control cells, TNF-alpha significantly stimulated NIH/3T3 cell
      proliferation, wherea. rhIL-10 had no such effect. With TNF-alpha stimulation,
      rhIL-10 at the dose as low as 1 ng/ml inhibited the proliferation of NIH/3T3
      cells (P<0.05). The number of cells in G(0)/G(1) phase treated with both TNF
      alpha and rhIL-10 was higher than those treated with TNF-alpha alone (P<<0.05),
      as shown by flow cytometry. CONCLUSION: rhIL-10 can significantly inhibit the
      proliferation of adventitial fibroblasts induced by TNF-alpha in vitro.

PMID- 14724097
TI  - [Neuroprotective effect of monoamine oxidase monoclonal antibody against
      vasogenic brain edema in rats].
AB  - OBJECTIVE: To observe the therapeutic effect of monoamine oxidase (MAO)
      monoclonal antibody (mAb) for vasogenic brain edema (VBE) in rats. METHODS: A
      total of 75 Wistar rats were randomized into non-edema, non-treated edema, saline
      treated edema, mannitol-treated edema and MAO mAb-treated groups. Rat models of
      VBE were established by intraperitoneal injection of phenylephrine in the latter
      4 groups. Brain water content in the gray and white matter was measured
      respectively with a moisture analyzer, and the permeability of the blood-brain
      barrier (BBB) determined by Evan's blue (EB) extravasation method. RESULTS: MAO
      mAb administration significantly reduced the brain water content in the gray and
      white matter as well as the permeability of BBB (P<0.01), Which was especially
      effective for the white matter, producing results comparable with those of the
      non-edema group (P>0.05). MAO mAb markedly alleviated brain edema, with better
      dehydrating effect on the white matter than mannitol (P<0.01), which reduced the
      water content of the brain gray and white matter undiscriminatingly and showed
      poor effect on the permeability of BBB. CONCLUSION: The pathogenesis of BBB
      permeability changes in VBE is related to the activity of monoamine oxidase, and
      MAO mAb has selective therapeutic effect on VBE, which is especially obvious on
      brain white matter.

PMID- 14724098
TI  - [Experimental study of the effect of Astragalus membranaceus against herpes
      simplex virus type 1].
AB  - OBJECTIVE: To study the inhibitory effects of Astragalus membranaceus on herpes
      simplex virus type 1(HSV-1). METHODS: In the 2BS cells infected with HSV-1, the
      antiviral effect of Astragalus membranaceus decoction was investigated by
      observing the inhibition of HSV-1-induced cytopathic effect in response to
      treatment with the decoction. RESULTS: The half inhibition concentration (IC50)
      and minimal inhibition concentration (MIC) of Astragalus membranaceus were 0.98
      and 1.95   g/ml respectively, with the therapeutic index (TI) of 128. CONCLUSION:
      Astragalus membranaceus has obvious HSV-1-inhibiting efficacy and low
      cytotoxicity.

PMID- 14724099
TI  - [Study on related factors of premature delivery and perinatal management].
AB  - OBJECTIVE: To study the etiological factors, perinatal management of premature
      delivery and the outcome of the premature infants. METHODS: The medical records
      of normal deliveries over the past 8 years in our hospital were respectively
      reviewed to analyze the difference between full-term and premature delivery cases
      in terms of maternal age, perinatal factors and manner of delivery. The states of
      birthing and outcomes of premature were reviewed. RESULTS: Preterm premature
      rupture of the membranes and in vitro fertilization-embryo transfer (IVF-ET) were
      the major causes of premature delivery, which was also related to such factors as
      placenta previa and pregnancy-induced hypertension. Premature delivery with
      unknown causes had been decreasing over these years. The maternal age and history
      of previous birth did not vary significantly between the full-term and the
      premature groups, but the later had significantly higher rates of cesarean
      section, in which 67.64% of the cases had Apgar scores <or=7. The state of the
      neonates and manner of delivery were significantly different between the two
      groups. In the premature infants, the incidences of hypoxic-anoxic
      encephalopathy, aspiration pneumonia and neonatal mortality were significantly
      higher than those in the full-term infants. CONCLUSIONS: Rigorous measures for
      preventing preterm premature rupture of the membranes and controlling transferred
      embryo numbers are crucial to prevent premature delivery. Good perinatal care and
      exact evaluation of the state of the parturient may also help reduce the
      incidence of premature delivery and improve the quality of life of the neonates.

PMID- 14724100
TI  - [Molecular genetic diagnosis and clinical analysis of spinocerebellar ataxia type
      7].
AB  - OBJECTIVE: To study the molecular genetic diagnosis and clinical characteristics
      of spinocerebellar ataxia type 7 (SCA7). METHODS: This study included 43 patients
      with autosomal dominant SCA from 36 families, 38 sporadic SCA patients, 60
      healthy individuals from the SCA families and 44 normal controls without family
      SCA history. The SCA7 (CAG)n mutations were detected by PCR, denaturing
      polyacrylamide gel electrophoresis and silver staining technique. The abnormal
      allele fragments were sequenced by ABI373 DNA sequencing machine. RESULTS: Normal
      alleles of SCA7 were found to have 9 to 19 CAG repeats. Two familial SCA and one
      sporadic patients were identified by detecting the presence of abnormal CAG
      repeat expansion in the SCA7 alleles, which was confirmed by DNA sequencing. The
      repeats of CAG were 65, 65, and 63 respectively. CONCLUSIONS: Abnormal CAG
      expansion is the pathogenic cause of SCA7. Molecular genetic analysis is
      effective for the diagnosis of SCA, prediction of presymptomatic patients and
      genetic counseling.

PMID- 14724101
TI  - [Application of ischemic preconditioning before hepatic vascular exclusion for
      resection of hepatocellular carcinoma].
AB  - OBJECTIVE: To assess the value of clinical application of ischemic
      preconditioning (IP) before hepatic vascular exclusion for resection of
      hepatocellular carcinoma (HCC) accompanied by cirrhosis and explore the possible
      mechanism underlying the protective effect of this maneuver. METHODS: Thirty-four
      consecutive patients with resectable HCC were randomized into IP group to receive
      IP with a 5-min ischemia followed by 5-min perfusion before hepatic vascular
      exclusion and the control group with simply hepatic vascular exclusion. The liver
      function, hepatic Fas mRNA expression, caspase-3 activity, apoptosis of the
      hepatocytes were compared between the two groups. RESULTS: In the IP group, the
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels on
      postoperative day 1, 3 and 7 were all significantly higher than those of the
      control group (t=6.985, P<0.01). The total bilirubin levels were also higher in
      the former group on postoperative day 3 and 7 (t=3.447, P<0.05). The IP group had
      higher albumin levels on postoperative day 1 than the control group (t=3.360,
      P<0.05). After 1 hour's reperfusion, the hepatic mRNA expression of Fas, caspase
      3 activity and apoptotic sinusoidal endothelial cells were all significantly
      higher than those of the control group (t=3.771, P<0.05). CONCLUSION: IP has a
      protective effect on liver function after hepatic resection with hepatic vascular
      exclusion in HCC patients, possibly due to the inhibition of hepatocyte apoptosis
      by down-regulating hepatic Fas mRNA expression and caspase-3 activity, and is a
      convenient technique applicable in such operations as hepatic transplants and
      hepatectomy.

PMID- 14724102
TI  - [Expression of vascular endothelial growth factor and endostatin in peritoneal
      fluid of patients with endometriosis].
AB  - OBJECTIVE: To investigate the relationship of vascular endothelial growth factor
      (VEGF) and endostatin with endometriosis. METHODS: The levels of vascular
      endothelial growth factor and endostatin were measured using ELISA in 50 women
      with endometriosis (stage I-II26 cases and stage III-IV 24 cases) in comparison
      with 42 women without endometriosis. RESULTS: The VEGF, endostatin concentrations
      and VEGF/endostatin ratio in endometriosis group were significantly higher than
      the mean value in the control group (P<0.01). The VEGF and endostatin levels in
      stages III and IV were both significantly higher than those in stages I and
      II(397+/-81 pg/ml vs 315+/-64 pg/ml, 125+/-62 ng/ml vs 66+/-40 ng/ml, P<0.01).
      However, the VEGF/endostatin ratio was lower in the advanced stages. There was no
      significant difference between follicular phase and luteal phase except that the
      VEGF level in follicular phase was higher than that in luteal phases.
      CONCLUSIONS: Both VEGF and endostatin may play a role in the regulation of
      angiogenesis of endometriosis, and the balance of angiogenic stimulators and
      inhibitors may be critical to the development of endometriosis.

PMID- 14724103
TI  - [Electron microscopic observations of alveoli development and epithelial
      differentiation in the fetal lung of the Chinese].
AB  - OBJECTIVE: To observe the development of the alveoli and the differentiation of
      the epithelium in the fetal lung of Chinese. METHODS: Chinese human lung tissues
      were obtained from 20 fetuses of 10 to 34 weeks old, and the ultrastructural
      changes of the alveolar epithelial cells were observed using both optical and
      transmission electron microscope. RESULTS: At the first 10 to 16 weeks of
      development, the lung showed a tubular structure, the epithelial cells were
      columnar and poorly differentiated. At weeks 17 to 24, the bronchioles increased
      and the epithelial cells were differentiated to approach maturity. A few lamellar
      bodies were observed in the cuboidal lining cells with the majority being type II
      alveolar cells at 25 weeks, when the primitive alveolar was formed. In this stage
      many primitive epithelial cells could be seen, which appeared primordial in form
      before evolving into type II and type I cells and perhaps served as epithelial
      stem cells or progenitor cells. From about 26 weeks, type I cells were observed
      but most of the epithelial cells were type II cells. Type I cells began to
      increase in the alveolar epithelium until 32 weeks. CONCLUSIONS: The alveolar
      type II cells and type I cells are probably both derived from the same precursor
      cells or stem cells, and no evidence has shown that type II cells may
      differentiate into type I cells during the development of the fetal lung.

PMID- 14724104
TI  - [Expression of nuclear factor-kappaBP65 in human brain glioma and human brain
      metastatic carcinoma and its significance].
AB  - OBJECTIVE: To study the immunohistochemical changes of nuclear factor-kappaBP65
      (NF-kappaBp65) in human brain glioma (HBG) and human brain metastatic carcinoma
      (HBMC) and the role of NF-kappaBP65 in the biological behavior of the tumors.
      METHODS: The protein expression of NF-kappaBP65 were examined with SABC
      immunohistochemical technique in 18 HBG, 12 HBMC and 6 normal brain tissue
      samples, and the correlation between the expression and the biological behavior
      of the tumors was analyzed. RESULTS: Normal brain tissues had only trace
      expression of NF-kappaBP65, whereas all tumor tissues examined expressed NF
      kappaBP65. The level of NF-kappaBP65 in high-grade HBG, HBMC and recurrent HBG
      tissues was considerably higher than that in low-grade HBG tissues (PLT;0.01).
      CONCLUSION: NF-kappaBP65 expression is associated with the malignant progression,
      invasion and angiogenesis of HBG and HBMC, and it may play a crucial role in the
      recurrence of HBG.

PMID- 14724105
TI  - [Electron microscopic observation of primary cultured laterally spreading tumor
      cell line].
AB  - OBJECTIVE: To observe the microscopic characteristics of laterally spreading
      tumor (LST) cell line in primary culture. METHODS: The cells isolated from a
      rectum LST specimen obtained by endoscopic mucosal resection was primary
      cultured, followed by observation with scanning and transmission electron
      microscope in comparison with the cells of adenocarcinoma and normal mucosa of
      the rectum. RESULTS: Scanning and transmission electron microscopes both revealed
      numerous microvilli covering the surface of the LST cells, and the cytoplasm
      contained large quantity of lysosomes, mitochondria and phagosomes. Obviously
      heterogeneous cell nuclei were present with abnormal nuclear fossa and huge
      nucleoli. CONCLUSION: The cultured LST cells are highly malignant.

PMID- 14724106
TI  - [Use of unfractionated heparin and a low-molecular-weight heparin following
      thrombolytic therapy for acute ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To compare the efficacy and safety of unfractionated heparin with a
      low-molecular-weight heparin (parnaparin) in the management of anticoagulation
      following thrombolytic therapy for acute ST-segment elevation myocardial
      infarction. METHODS: One hundred and eighty-six patients with acute ST-segment
      elevation myocardial infarction undergoing thrombolytic therapy were randomly
      assigned to receive either unfractionated heparin (100 U/kg x b.w. intravenous
      bolus, 1,000 U/h continuous infusion for 3 days just 12 h after thrombolysis to
      maintain the activated partial thromboplastin time at 1.5 to 2.0 times as normal,
      then subcutaneous 7500 U every 12 h for 4 days, n=90) or parnaparin (0.4 ml
      subcutaneously every 12 h for 7 days 12 h after thrombolysis, n=96) in
      conjunction with routine therapy. The patients enrolled stayed in hospital for at
      least 14 days and were followed for 45 days after admission into the hospital.
      RESULTS: The composite triple end-point (death, recurrent myocardial infarction,
      emergency revascularization assessed at 2, 7, 14, 45 days) was significantly
      reduced in patients receiving parnaparin 42.22% vs 37.08%, P=0.03 . Compared with
      unfractionated heparin group, the incidences of hemorrhage 10.00% vs 3.13%,
      P=0.06 and heparin-induced thrombocytopenia (3.33% vs 0, P=0.07) were also lower
      in parnaparin group. CONCLUSION: Parnaprin is more effective in reducing
      composite cardiac events, hemorrhage and heparin-induced thrombocytopenia at
      least in 45 days as compared with unfractionated heparin during anticoagulation
      following thrombolytic therapy for acute ST-segment elevation myocardial
      infarction.

PMID- 14724107
TI  - [Autophagic effect of Schwann cells in the regeneration of rat sciatic nerves].
AB  - OBJECTIVE: To investigate the autophagic effect of Schwann cells in the process
      of rat sciatic nerve regeneration. METHODS: Wallerian degeneration model was
      established by transecting the rat sciatic nerve. Samples from the distal stump
      were obtained 0, 0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, and 15 days respectively after
      the transaction, and ultrathin sections were prepared for examination with
      electron microscope. RESULTS: Axons started to separate from the myelin sheath at
      day 0.5 after the transection, followed by rapid vacuolar degeneration. Since day
      2, the myelin sheath folded and broke into fragments, and in the Schwann cells
      large cell membrane-bound myelin debris and many scattered small fragments could
      be seen to fuse with the lysosomes to form ACPase reaction-positive autophagic
      vacuoles. Immature cells were occasionally seen in the endoneural space,
      appearing in large amount a week later. After day 7, the number of autophagic
      vacuoles began to diminish. In the entire course of the observation, macrophages
      containing autophagic vacuoles, were spotted only occasionally. CONCLUSION: The
      degenerated myelin debris are cleared mainly through the mechanism of autophagy
      by the Schwann cells during regeneration of rat sciatic nerve. Schwann cells
      dedifferentiate into Schwann cell precursors, which then proliferate and
      differentiate to take part in the regeneration of the nerves.

PMID- 14724108
TI  - [Hepatosplenic gammadeltaT-cell lymphoma: a clinicopathological study].
AB  - OBJECTIVE: To explore the clinicopathologic features and immunophenotype of
      hepatosplenic gammadeltaT-cell lymphoma. METHODS: A case of hepatosplenic
      gammadeltaT-cell lymphoma was studied with conventional histopathological and
      immunohistochemical staining in combination of literature review. RESULTS:
      Diffuse hepatic and splenic enlargement was found in this case. Microscopically,
      the liver and spleen showed marked sinusoidal infiltration. The cells of
      hepatosplenic T-cell lymphoma were homogeneous, medium in size with pale
      cytoplasm, and the nuclear chromatin was loosely condensed with small
      inconspicuous nucleoli. The neoplastic cells were positive for CD45RO, CD3 and
      TIA-1, but negative for CD57, CD20 and CD79a. CONCLUSION: Hepatosplenic
      gammadeltaT-cell lymphoma is a rare form of peripheral T-cell lymphoma and has
      usually poor prognosis, which should be differentiated from other lymphomas or
      leukemia.

PMID- 14724109
TI  - [Exploration of the treatment for the periprosthetic femoral fractures].
AB  - OBJECTIVE AND METHODS: To investigate the clinical value of the different
      managements of periprosthetic femoral fractures (PFF). A retrospective study of
      16 cases with PFF fixed respectively with cable, plates and screws, encircling
      device and altered long stem prosthesis was undertaken. RESULTS: Clinical and
      functional results were followed-up from 4 to 14 months with an average of 6
      months. All the fractures were healed with excellent functional recoveries. Three
      of these cases scored above 90; 9 cases scored 80 to 89; 3 cases scored 70 to 79;
      and 1 case scored 63 according to the functional evaluation. The success rate of
      these treatments was 75%. CONCLUSIONS: Different types of PFF should be treated
      with different methods. Cable with stainless steel cerclage was used for fissure
      fracture from the femoral neck to lesser trochanter; a smaller type of prosthesis
      was grafted and then fixed with the cable for complete fissure fracture; longer
      prosthetic stem graft replacement accompanied by cable fixation, and locked
      nailing or encircling devices for distant part of the graft, were recommended for
      fractures happened from inferior edge of lesser trochanter to superior margin of
      narrowed segment of femoral stem. Steel plate or encircling devices fixation with
      bone graft is suitable for fractures occurred on inferior part of narrowed
      segment of femoral stem marrow.

PMID- 14724110
TI  - [Comparative anatomical study of three surgical approaches for treating complex
      posterior urethral stricture].
AB  - OBJECTIVE: To evaluate the advantages and disadvantages of 3 surgical approaches
      via superior intermedial margin of the pubis, inferior medial margin of the
      pubis, and the perineum, respectively, in the treatment of posterior urethral
      stricture. METHODS: Thirty-five adult male corpses were dissected in which the
      distances from the bulbo-membranous urethra conjunction (D), the apex of prostate
      (E), and the bladder neck (F) to the superior medial margin of the pubis (A), the
      inferior medial margin of the pubis (B) and the midpoint of linear distance
      between the two ischial tuberosities on the perineum (C) were respectively
      measured and compared. Another 20 adult male corpses were subjected to the 3
      surgical approaches as described above and the urethra was exposed to identify
      the tissues and organs with possible injuries resulted from the surgery, which
      were evaluated by scoring. RESULTS: The distances measured were as follows:
      AD=6.5+/-0.5 cm, BD=2.2+/-0.5 cm, CD =3.4+/-0.6 cm, and BD<CD<AD (P=0.05, SNK
      means); AE=6.6+/-0.5 cm, BE=3.0+/-0.5 cm, CE=4.4+/-0.7 cm, and BE<CE<AE (P=0.05,
      SNK means); AF=5.7+/-0.6 cm, BF=4.5+/-0.5 cm, CF=6.5+/-0.6 cm, and BF<AF<CF
      (P=0.05, SNK means). The angles EAD (alpha1)=(9.3+/-2.0)(degrees), EBD
      (alpha(2))=(17.4+/-3.8)(degrees), ECD (alpha(3))=(9.2+/-1.6)(degrees), showing
      marked difference between alpha(1) and alpha(2) (P<0.05, t=11.1) and between
      alpha(3) and alpha(2) (P<0.05, t=12.1), but not between alpha(1) and alpha(3)
      (P>0.05, t=0.13). The angles FAE (beta(1)) =(22.7+/-2.6)(degrees), FBE
      (beta(2))=(32.9+/-6.4)(degrees), FCE (beta(3))=(15.0+/-3.2)(degrees), and beta(2)
      beta(1) beta(3) (P=0.05, SNK means). The score for tissue and organ injuries for
      the approach of the superior medial margin of the pubis was 13, 20 for the
      approach of inferior medial margin of the pubis, and 15 for perineum approach.
      CONCLUSIONS: In terms of operative field exposure, the best operation approach is
      via the inferior pubis, followed by superior pubis approach and perineum
      approach; while in view of the injuries, superior pubis approach is better than
      the perineum and inferior pubis approaches. The inferior pubis approach should be
      the primary choice in the treatment of posterior urethral stricture.

PMID- 14724111
TI  - [Application of two parallel Kirschner wires in internal fixation for digital
      replantation: experience with 14 cases].
AB  - OBJECTIVE: To improve the method for internal fixation in digital replantation.
      METHOD: In 14 cases of finger fractures (17 fingers) admitted in our hospital
      between October, 2000 and March, 2003, intramedullary fixation was performed with
      two-parallel Kirschner wires, and the effects were compared with those of other
      internal fixations in cases treated within the same period. RESULT: All the
      digital fractures healed and none of the 10 patients followed up suffered
      nonunion or delayed healing. The average healing time of the fractures was 5
      weeks, and the joint function recovered satisfactorily. CONCLUSION: Internal
      fixation with two parallel Kirschner wires can achieve more reliable fixation to
      promote the healing of the bone fractures.

PMID- 14724112
TI  - [Detection of carbonic anhydrase IX gene expression in renal cell carcinoma with
      reverse transcription-PCR].
AB  - OBJECTIVE: To evaluate the reliability of reverse transcription (RT)-PCR in
      detecting the expression of the carbonic anhydrase IX (MN/CAIX) gene in renal
      cell carcinoma (RCC). METHODS: MN/CAIX was examined in 5 cases of renal cell
      carcinoma tissues and 5 normal renal tissues. Primers specific for MN/CAIX was
      designed and two-step RT-PCR of the extracted total RNA performed. The products
      was examined by 2% agarose electrophoresis and identified by sequence analysis.
      RESULTS: Specific bands of MN/CAIX were found in RT-PCR products of 4 case of RCC
      tissues, whereas could not be seen in normal renal tissues. CONCLUSION: RT-PCR is
      reliable for detecting the expression of MN/CAIX gene in RCC.

PMID- 14724113
TI  - [Detection of serum S100 protein and tissue polypeptide-specific antigen for
      diagnosis and treatment of breast cancer].
AB  - OBJECTIVE: To investigate the expressions of serum S100 protein and tissue
      polypeptide-specific antigen (TPS) in breast cancer and their clinical
      implications. METHODS: Using enzyme-linked immunosorbent assay, the levels of
      serum S100 protein and TPS were determined in 48 breast cancer patients as well
      as in 92 control subjects. RESULTS: The median level of serum S100 protein and
      TPS were 0.024 microg/L and 135 U/L respectively in the 48 breast cancer
      patients, among whom their positive rates were 14.6% (7/48) and 50% (24/48)
      respectively; in stage IV patients, their positive rates were 70% (7/10) and 60%
      (6/10) respectively. The levels of the serum S100 protein and TPS tended to
      increase as the disease advanced, and serum S100 protein level was significantly
      higher in patients with distal metastasis than in those with local relapse of the
      tumor. CONCLUSION: Progressively elevated levels of serum S100 protein and TPS
      signify the deterioration of breast cancer, and can be used to estimate the stage
      and state of breast cancer.

PMID- 14724114
TI  - [Long-term curative effect of ventilation tube insertion for otitis media with
      effusion in adult patients].
AB  - OBJECTIVE: To examine the long-term effect of ventilation tube insertion in
      treating patients with non-tumor adult-onset otitis media with effusion (OME).
      METHODS: During the period from 1999 to 2001, a total of 153 adult patients
      received ventilation tube insertion for OME and were followed up for 12-18 months
      postoperatively. A retrospective analysis of these cases was conducted. RESULTS:
      Out of the 153 patients, 81 had received at least one previous operation of
      ventilation tube insertion. During 12-18 months following the operation, the
      ventilation tubes were extruded in 89 patients, among whom 55 had OME recurrence.
      The recurrence of OME following ventilation tube extrusion was significantly
      correlated to the pathological changes in the nose or nasopharynx of the
      patients. CONCLUSION: The underlying pathological changes may lead to recurrence
      of adult-onset OME following extrusion of the ventilation tube, therefore, better
      long-term outcome may be expected only after identifying the underlying
      pathological changes and giving them appropriate treatment in addition to
      ventilation tube insertion.

PMID- 14724115
TI  - [Analyses of ultrasonographs of adrenal gland cysts in comparison with
      pathological findings].
AB  - OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of
      adrenal gland cysts. METHODS: Six patients with adrenal gland cysts were examined
      by two-dimensional ultrasonography and color Doppler flow imaging (CDFI), and the
      results were compared with the pathological findings. RESULTS: The diagnoses by
      ultrasonography and CDFI were consistent with the pathological findings in 5
      cases. CONCLUSION: Ultrasonography and CDFI can be an accurate diagnostic
      modality for adrenal gland cysts.

PMID- 14724116
TI  - [Analysis of the causes of hospital death in aged diabetics].
AB  - OBJECTIVE: To understand the mortality rate and main death causes of aged
      diabetics in hospital. METHODS: The clinical record of 183 aged diabetic
      patients, who were hospitalized and died between January, 1995 and December, 2002
      in our hospital, were reviewed in comparison with 293 non-diabetic aged patients
      hospitalized in the same period. RESULTS: The mortality rate of the aged
      diabetics was 13.11%, far beyond that of the non-diabetics. The main death causes
      of the diabetic patients were tumor (29.5%), cardiovascular diseases (CVD,
      25.7%), pulmonary infections (14.2%), renal dysfunction (9.8%) and cerebral
      vascular diseases (5.5%). Tumor was the main cause of death in the diabetic
      patients 60 to 80 years of age, and in those 80-90 years old, CVD accounted for
      most of the deaths, whereas most patients over 90 years old died of pulmonary
      infections. When only one of the 3 risk factors, namely hypertension,
      dyslipidemia and smoking, was present, CVD accounted for 36.8% of all deaths;
      when all the 3 factors co-existed, CVD accounted for 50% of all deaths.
      CONCLUSIONS: The mortality rate of aged diabetics is higher than that of the non
      diabetics. Tumor and CVD are the main causes of death, but the constituent ratio
      changes with age. The ratio of CVD in all death causes depends on the number of
      risk factors present, including hypertension, dyslipidemia and smoking.

PMID- 14724117
TI  - [Repair of urethral fistula resulting from correction of hypospadias: experience
      with 56 cases].
AB  - OBJECTIVE: To improve the success rate of one-stage urethral fistula repair by
      modifying the surgical procedures, suture material and application of urethral
      stent. METHODS: The clinical data of 56 cases of urethral fistula following
      correction of hypospadias were analyzed. The case group consisted of 38 cases
      with large fistula (over 3 mm in diameter) and 18 cases of small fistula (less
      than 3 mm). For the former cases, double skin flaps or pedicled skin flap from
      the scrotum were adopted for the repair; in the latter cases, transverse Y- or V
      shaped skin flaps were used. Porous silica gel cannula was adopted for the
      stents. RESULT: A success rate of one-stage repair as high as 87.50% was achieved
      in these cases, with a rate for large fistula of 86.84%. CONCLUSION: Rich blood
      supply of the flaps, application of absorbable suture and urethral stent can
      improve the success rate of fistula repair.

PMID- 14724118
TI  - [Experience with coronary artery bypass grafting and concomitant procedures in 21
      cases].
AB  - OBJECTIVE: To review our experience with coronary artery bypass grafting (CABG)
      and its concomitant procedures. METHODS: From December, 1998 to December, 2002,
      21 patients underwent CABG and their clinical data were analyzed. RESULTS:
      Nineteen patients were discharged uneventfully after the procedure. Early death
      occurred in 2 patients who received emergency operation after acute myocardial
      infarction. Among the 18 patients followed up, angina was eliminated in all but
      one patient. CONCLUSION: Although the concomitant procedures such as valve
      replacement may prolong the operation time for CABG, good clinical outcome of the
      patients can still be expected by implementation of intensive perioperative
      management and complete myocardial revascularization.

PMID- 14724119
TI  - [An easier method for generating recombinant adenovirus containing CD/TK fusion
      gene driven by vascular endothelial growth factor promoter].
AB  - OBJECTIVE: To efficiently construct the recombinant adenovirus containing CD/TK
      fusion gene driven by vascular endothelial growth factor (VEGF) promoter using
      improved homologous recombination in bacteria. METHODS: Chemical transformation,
      instead of electroporation, of the plasmid pAdEasy-1 into E.coli BJ5183 strain
      was performed to prepare BJ5183pAdEasy-1 as the competent bacterium, in which
      pAdEasy-1 and pAdtrack-VEGFP-CDglyTK were recombined. Finally, the recombinant
      adenovirus of AdVEGFP-CDglyTK was constructed by transfecting 293 cells with
      linearized adenoviral genomes of pAdEasy-VEGFP-CDglyTK. RESULTS: This new
      transformation procedure generated recombinant plasmids in a yield of 60% (6/10),
      and the adenovirus AdVEGFP-CDglyTK was harvested 7-12 d after transfection.
      CONCLUSION: The improved homologous recombination in bacteria is efficient,
      convenient and easy to be carried out.

PMID- 14724120
TI  - Fitness estimation through performance comparison of F1 hybrids with their
      parental species Oryza rufipogon and O. sativa.
AB  - BACKGROUND AND AIMS: Introgression of crop genes into populations of wild
      relatives has important implications for germplasm conservation as well as for
      the persistence of novel transgenes in wild populations. Studies of hybrid
      fitness can be used to evaluate the potential for introgression to occur
      following episodes of interspecific hybridization. METHODS: This study estimated
      relative fitness of interspecific hybrids through performance comparison of F(1)
      hybrids with their parental species, a cultivated rice (Oryza sativa) Minghui-63
      and perennial common wild rice (O. rufipogon) under the cultivation conditions.
      KEY RESULTS: Compared with their parents, the hybrids had the lowest values of
      seedling survival ability, pollen viability and seed production; intermediate
      values of seed germination, spikelet production and flag leaf areas; and the
      highest values of plant height, number of tillers and panicles. The hybrids
      performed poorly at the stage of sexual reproduction, although they had a
      slightly higher hybrid vigour at the vegetative growth stage and better tillering
      ability than their wild parent. There were no significant differences in
      composite fitness across the whole life-history between the hybrids and their
      wild parental species. CONCLUSIONS: Rice genes, including transgenes, might
      persist in wild rice populations through vegetative and sexual reproduction.
      Further studies are needed to examine whether the extent of gene flow from rice
      is sufficiently significant to influence genetic diversity in wild populations of
      O. rufipogon, a species that has become endangered in some regions of south-east
      Asia.

PMID- 14724121
TI  - Genome size variation among accessions of Arabidopsis thaliana.
AB  - BACKGROUND AND AIMS: Estimates of the amount of nuclear DNA of Arabidopsis
      thaliana, known to be among the lowest within angiosperms, vary considerably.
      This study aimed to determine genome size of a range of accessions from
      throughout the entire Eurasian range of the species. METHODS: Twenty accessions
      from all over Europe and one from Japan were examined using flow cytometry. KEY
      RESULTS: Significant differences in mean C-values were detected over a 1.1-fold
      range. Mean haploid (1C) genome size was 0.215 pg (211 Mbp) for all analysed
      accessions. Two accessions were tetraploid. CONCLUSIONS: A closer investigation
      of the DNA fractions involved in intraspecific genome size differences in this
      experimentally accessible species may provide information on the factors involved
      in stability and evolution of genome sizes.

PMID- 14724122
TI  - Drosophila dMyc is required for ovary cell growth and endoreplication.
AB  - Although the Myc oncogene has long been known to play a role in many human
      cancers, the mechanisms that mediate its effects in both normal cells and cancer
      cells are not fully understood. We have initiated a genetic analysis of the
      Drosophila homolog of the Myc oncoprotein (dMyc), which is encoded by the dm
      locus. We carried out mosaic analysis to elucidate the functions of dMyc in the
      germline and somatic cells of the ovary during oogenesis, a process that involves
      cell proliferation, differentiation and growth. Germline and somatic follicle
      cells mutant for dm exhibit a profound decrease in their ability to grow and to
      carry out endoreplication, a modified cell cycle in which DNA replication occurs
      in the absence of cell division. In contrast to its dramatic effects on growth
      and endoreplication, dMyc is dispensable for the mitotic division cycles of both
      germline and somatic components of the ovary. Surprisingly, despite their
      impaired ability to endoreplicate, dm mutant follicle cells appeared to carry out
      chorion gene amplification normally. Furthermore, in germline cysts in which the
      dm mutant cells comprised only a subset of the 16-cell cluster, we observed
      strictly cell-autonomous growth defects. However, in cases in which the entire
      germline cyst or the whole follicular epithelium was mutant for dm, the growth of
      the entire follicle, including the wild-type cells, was delayed. This observation
      indicates the existence of a signaling mechanism that acts to coordinate the
      growth rates of the germline and somatic components of the follicle. In summary,
      dMyc plays an essential role in promoting the rapid growth that must occur in
      both the germline and the surrounding follicle cells for oogenesis to proceed.

PMID- 14724123
TI  - Ectopic Myf5 or MyoD prevents the neuronal differentiation program in addition to
      inducing skeletal muscle differentiation, in the chick neural tube.
AB  - Forced expression of the bHLH myogenic factors, Myf5 and MyoD, in various
      mammalian cell lines induces the full program of myogenic differentiation.
      However, this property has not been extensively explored in vivo. We have taken
      advantage of the chick model to investigate the effect of electroporation of the
      mouse Myf5 and MyoD genes in the embryonic neural tube. We found that
      misexpression of either mouse Myf5 or MyoD in the chick neural tube leads to
      ectopic skeletal muscle differentiation, assayed by the expression of the myosin
      heavy chains in the neural tube and neural crest derivatives. We also showed that
      the endogenous neuronal differentiation program is inhibited under the influence
      of either ectopic mouse Myf5 or MyoD. We used this new system to analyse, in
      vivo, the transcriptional regulation between the myogenic factors. We found that
      MyoD and Myogenin expression can be activated by ectopic mouse Myf5 or MyoD,
      while Myf5 expression cannot be activated either by mouse MyoD or by itself. We
      also analysed the transcriptional regulation between the myogenic factors and the
      different genes involved in myogenesis, such as Mef2c, Pax3, Paraxis, Six1, Mox1,
      Mox2 and FgfR4. We established the existence of an unexpected regulatory loop
      between MyoD and FgfR4. The consequences for myogenesis are discussed.

PMID- 14724124
TI  - The Sp8 zinc-finger transcription factor is involved in allometric growth of the
      limbs in the beetle Tribolium castaneum.
AB  - Members of the Sp gene family are involved in a variety of developmental
      processes in both vertebrates and invertebrates. We identified the ortholog of
      the Drosophila Sp-1 gene in the red flour beetle Tribolium castaneum, termed T
      Sp8 because of its close phylogenetic relationship to the vertebrate Sp8 genes.
      During early embryogenesis, T-Sp8 is seen in segmental stripes. During later
      stages, TSp8 is dynamically expressed in the limb buds of the Tribolium embryo.
      At the beginning of bud formation, TSp8 is uniformly expressed in all body
      appendages. As the limbs elongate, a ring pattern develops sequentially and the
      expression profile at the end of embryogenesis correlates with the final length
      of the appendage. In limbs that do not grow out like the labrum and the labium, T
      Sp8 expression remains uniform, whereas a two-ring pattern develops in the longer
      antennae and the maxillae. In the legs that elongate even further, four rings of
      T-Sp8 expression can be seen at the end of leg development. The role of T-Sp8 for
      appendage development was tested using RNAi. Upon injection of double stranded T
      Sp8 RNA, larvae develop with dwarfed appendages. Affected T-Sp8(RNAi) legs were
      tested for the presence of medial and distal positional values using the
      expression marker genes dachshund and Distal-less, respectively. The results show
      that a dwarfed TSp8(RNAi) leg consists of proximal, medial and distal parts and
      argues against T-Sp8 being a leg gap gene. Based on the differential expression
      pattern of T-Sp8 in the appendages of the head and the thorax and the RNAi
      phenotype, we hypothesise that T-Sp8 is involved in the regulation of limb-length
      in relation to body size - a process called allometric growth.

PMID- 14724125
TI  - Moesin contributes an essential structural role in Drosophila photoreceptor
      morphogenesis.
AB  - Ezrin-Radixin-Moesin (ERM) family proteins organize heterogeneous sub-plasma
      membrane protein scaffolds that shape membranes and their physiology. In
      Drosophila oocytes and imaginal discs, epithelial organization, fundamental to
      development and physiology, is devastated by the loss of Moesin. Here, we show
      that Moesin is crucial for Drosophila photoreceptor morphogenesis. Beyond its
      requirement for retinal epithelium integrity, Moesin is essential for the proper
      assembly of the apical membrane skeleton that builds the photosensitive membrane,
      the rhabdomere. Moesin localizes to the rhabdomere base, a dynamic locus of
      cytoskeletal reorganization and membrane traffic. Downregulation of Moesin
      through RNAi or genetic loss of function profoundly disrupts the membrane
      cytoskeleton and apical membrane organization. We find normal levels and
      distribution of Moesin in photoreceptors of a Moesin mutant previously regarded
      as protein null, suggesting alternative interpretations for studies using this
      allele. Our results show an essential structural role for Moesin in photoreceptor
      morphology.

PMID- 14724126
TI  - C. elegans SUR-6/PR55 cooperates with LET-92/protein phosphatase 2A and promotes
      Raf activity independently of inhibitory Akt phosphorylation sites.
AB  - Protein phosphatase 2A (PP2A) can both positively and negatively influence the
      Ras/Raf/MEK/ERK signaling pathway, but its relevant substrates are largely
      unknown. In C. elegans, the PR55/B regulatory subunit of PP2A, which is encoded
      by sur-6, positively regulates Ras-mediated vulval induction and acts at a step
      between Ras and Raf. We show that the catalytic subunit (C) of PP2A, which is
      encoded by let-92, also positively regulates vulval induction. Therefore SUR
      6/PR55 and LET-92/PP2A-C probably act together to dephosphorylate a Ras pathway
      substrate. PP2A has been proposed to activate the Raf kinase by removing
      inhibitory phosphates from Ser259 from Raf-1 or from equivalent Akt
      phosphorylation sites in other Raf family members. However, we find that mutant
      forms of C. elegans LIN-45 RAF that lack these sites still require sur-6.
      Therefore, SUR-6 must influence Raf activity via a different mechanism. SUR-6 and
      KSR (kinase suppressor of Ras) function at a similar step in Raf activation but
      our genetic analysis suggests that KSR activity is intact in sur-6 mutants. We
      identify the kinase PAR-1 as a negative regulator of vulval induction and show
      that it acts in opposition to SUR-6 and KSR-1. In addition to their roles in Ras
      signaling, SUR-6/PR55 and LET-92/PP2A-C cooperate to control mitotic progression
      during early embryogenesis.

PMID- 14724127
TI  - Desmin myopathy.
AB  - Desmin myopathy is a recently identified disease associated with mutations in
      desmin or alphaB-crystallin. Typically, the illness presents with lower limb
      muscle weakness slowly spreading to involve truncal, neck-flexor, facial, bulbar
      and respiratory muscles. Skeletal myopathy is often combined with cardiomyopathy
      manifested by conduction blocks and arrhythmias resulting in premature sudden
      death. Sections of the affected skeletal and cardiac muscles show abnormal fibre
      areas containing amorphous eosinophilic deposits seen as granular or
      granulofilamentous material on electron microscopic examination. Immuno-staining
      for desmin is positive in each region containing abnormal structures. The
      inheritance pattern in familial desmin myopathy is autosomal dominant or
      autosomal recessive, but many cases have no family history. At least some, and
      probably most, non-familial desmin myopathy cases are associated with de novo
      desmin mutations. Age of disease onset and rate of progression may vary depending
      on the type of inheritance and location of the causative mutation. Multiple
      mutations have been identified in the desmin gene: point substitutions,
      insertion, small in-frame deletions and a larger exon-skipping deletion. The
      majority of these mutations are located in conserved alpha-helical segments of
      desmin. Many of the missense mutations result in changing the original amino acid
      into proline, which is known as a helix breaker. Studies of transfected cell
      cultures indicate that mutant desmin is assembly-incompetent and able to disrupt
      a pre-existing filamentous network in dominant-negative fashion. Disease
      associated desmin mutations in humans or transgenic mice cause accumulation of
      chimeric intracellular aggregates containing desmin and other cytoskeletal
      proteins. alphaB-crystallin serves in the muscle as a chaperone preventing desmin
      aggregation under various forms of stress. If mutated, alphaB-crystallin may
      cause a myopathy similar to those resulting from desmin mutations. Routine
      genetic testing of patients for mutations in desmin and alphaB- crystallin genes
      is now available and necessary for establishing an accurate diagnosis and
      providing appropriate genetic counselling. Better understanding of disease
      pathogenesis would stimulate research focused on developing specific treatments
      for these conditions.

PMID- 14724128
TI  - Outcome of subsequent pregnancy three years after previous operative delivery in
      the second stage of labour: cohort study.
AB  - OBJECTIVE: To evaluate the reproductive outcome and the mode of delivery in
      subsequent pregnancies after instrumental vaginal delivery in theatre or
      caesarean section at full dilatation. DESIGN: Prospective cohort study. SETTING:
      Two urban hospitals with a combined total of 10 000 deliveries a year.
      PARTICIPANTS: A cohort of 393 women with term, singleton, cephalic pregnancies
      who needed operative delivery in theatre during the second stage of labour from
      February 1999 to February 2000. Postal questionnaires were received from 283
      women (72%) at three years after the initial delivery. MAIN OUTCOME MEASURE: Mode
      of delivery in the subsequent pregnancy. RESULTS: 140 women (49%) achieved a
      further pregnancy at three years. 91/283 (32%) women wished to avoid a further
      pregnancy. Women were more likely to aim for vaginal delivery (87% (47/54) v 33%
      (18/54); adjusted odds ratio 15.55 (95% confidence interval 5.25 to 46.04)) and
      more likely to have a vaginal delivery (78% (42/54) v 31% (17/54); 9.50 (3.48 to
      25.97)) if they had had a previous instrumental vaginal delivery rather than a
      caesarean section. There was a high rate of vaginal delivery after caesarean
      section among women who attempted vaginal delivery 17/18 (94%). In both groups,
      fear of childbirth was a frequently reported reason for avoiding a further
      pregnancy (51% after instrumental vaginal delivery, 42% after caesarean section;
      1.75 (0.58 to 5.25)). CONCLUSION: Instrumental vaginal delivery offers advantages
      over caesarean section for future delivery outcomes. The psychological impact of
      operative delivery requires urgent attention.

PMID- 14724129
TI  - Randomised controlled trial and economic evaluation of a chest pain observation
      unit compared with routine care.
AB  - OBJECTIVES: To measure the effectiveness and cost effectiveness of providing care
      in a chest pain observation unit compared with routine care for patients with
      acute, undifferentiated chest pain. DESIGN: Cluster randomised controlled trial,
      with 442 days randomised to the chest pain observation unit or routine care, and
      cost effectiveness analysis from a health service costing perspective. SETTING:
      The emergency department at the Northern General Hospital, Sheffield, United
      Kingdom. PARTICIPANTS: 972 patients with acute, undifferentiated chest pain (479
      attending on days when care was delivered in the chest pain observation unit, 493
      on days of routine care) followed up until six months after initial attendance.
      MAIN OUTCOME MEASURES: The proportion of participants admitted to hospital, the
      proportion with acute coronary syndrome sent home inappropriately, major adverse
      cardiac events over six months, health utility, hospital reattendance and
      readmission, and costs per patient to the health service. RESULTS: Use of a chest
      pain observation unit reduced the proportion of patients admitted from 54% to 37%
      (difference 17%, odds ratio 0.50, 95% confidence interval 0.39 to 0.65, P <
      0.001) and the proportion discharged with acute coronary syndrome from 14% to 6%
      (8%, -7% to 23%, P = 0.264). Rates of cardiac event were unchanged. Care in the
      chest pain observation unit was associated with improved health utility during
      follow up (0.0137 quality adjusted life years gained, 95% confidence interval
      0.0030 to 0.0254, P = 0.022) and a saving of pound 78 per patient (- pound 56 to
      pound 210, P = 0.252). CONCLUSIONS: Care in a chest pain observation unit can
      improve outcomes and may reduce costs to the health service. It seems to be more
      effective and more cost effective than routine care.

PMID- 14724130
TI  - Determination of genes involved in the early process of embryonic implantation in
      rhesus monkey (Macaca mulatta) by suppression subtractive hybridization.
AB  - Embryonic implantation is a temporally and spatially restricted process that
      involves a precise cross talk between the embryo and the receptive maternal
      endometrium. Underlying the complex changes in the uterus during implantation is
      the alteration in gene expression pattern, which is not fully understood for the
      primates. In the present study, suppression subtractive hybridization (SSH) was
      performed to screen genes that were differentially expressed in the implantation
      site of the pregnant rhesus monkey, and a subtractive cDNA library was
      constructed. Furthermore, with dot blot analysis, reverse Northern blot analysis,
      and semiquantitative reverse transcription-polymerase chain reaction, 76 of 376
      clones randomly selected from the library were proven to be differentially
      expressed in the implantation site. With DNA sequencing and BLAST analysis
      against the GenBank/EMBL database, it was demonstrated that the cDNA fragments
      carried by 73 clones shared high homology with 31 human genes. Among them, 15
      positive clones represented the S100A10 gene and 10 positive ones corresponded
      with the secreted frizzled-related protein 4 gene. The other two clones shared
      homology with one human EST. There was one clone homologous to a human DNA
      sequence, which indicated that it might be a novel gene. To our knowledge, this
      is the first report to determine genes involved in the early implantation stage
      in the rhesus monkey with high throughput technology.

PMID- 14724132
TI  - Cloning and expression of gonadotropin-releasing hormone receptor in the brain
      and pituitary of the European sea bass: an in situ hybridization study.
AB  - A full-length cDNA encoding a GnRH receptor (GnRH-R) has been obtained from the
      pituitary of the European sea bass, Dicentrarchus labrax. The complete cDNA is
      1814 base pairs (bp) in length and encodes a protein of 416 amino acids. The 5'
      UTR and 3' UTR are 239 bp and 324 bp in size, respectively. The expression sites
      of this GnRH-R were studied in the brain and pituitary of sea bass by means of in
      situ hybridization. A quantitative analysis of the expression of the GnRH-R gene
      along the reproductive cycle was also performed. The GnRH-R brain expression was
      especially relevant in the ventral telencephalon and rostral preoptic area. Some
      GnRH-R messenger-expressing cells were also evident in the dorsal telencephalon,
      caudal preoptic area, ventral thalamus, and periventricular hypothalamus. A
      conspicuous and specific GnRH-R expression was detected in the pineal gland. The
      highest expression of the GnRH-R gene was observed in the proximal pars distalis
      of the pituitary. This expression was evident in all LH cells and some FSH cells
      but not in somatotrophs. In the pituitary, the quantitative analysis revealed a
      higher expression of GnRH-R gene during late vitellogenesis in comparison with
      maturation, spawning, and postspawning/resting periods. However, in the brain,
      the highest GnRH-R expression was evident at spawning or postspawning/ resting
      periods. These results suggest that the expression of this GnRH-R is regulated in
      a different manner in the brain and the pituitary of sea bass.

PMID- 14724131
TI  - Acquisition of luteolytic capacity: changes in prostaglandin F2alpha regulation
      of steroid hormone receptors and estradiol biosynthesis in pig corpora lutea.
AB  - The pig corpora lutea (CL) acquires luteolytic capacity at about Day 13 of the
      estrous cycle, after which luteolysis occurs in response to prostaglandin F2alpha
      (PGF2alpha) treatment. We postulated that differences in transcription factors
      such as the steroid hormone receptors may be responsible for the differences in
      PGF2alpha-induced gene expression after acquisition of luteolytic capacity. In
      these studies, we evaluated the effect of PGF2alpha on luteal expression of
      receptors for progesterone (nuclear and membrane progesterone receptor [PR]),
      estradiol (ERalpha and ERbeta), glucocorticoid, androgens, and two enzymes in
      estradiol synthesis (P450-17alpha and aromatase). Two experiments were conducted
      to examine the early (0.5 h, experiment I) and late (10 h, experiment II) effects
      of PGF(2alpha) on the expression of these receptors in CL with (Day 17) or
      without (Day 9) luteolytic capacity. PGF2alpha decreased ERalpha mRNA (35%) and
      increased ERbeta mRNA (558%) and protein (376%) only in Day 17 CL and not Day 9.
      The estradiol biosynthetic pathway was upregulated by PGF2alpha in Day 17 CL but
      not Day 9 CL, with a dramatic increase in aromatase mRNA and luteal estradiol
      content. Nuclear PR was not affected by PGF2alpha, but was greater (176%) in Day
      9 CL, while a putative membrane PR was greater (156%) in Day 17 than Day 9 CL.
      There were no detectable changes in glucocorticoid or androgen receptor mRNA.
      Thus, luteolytic capacity is associated with upregulation of estradiol
      biosynthesis, which in conjunction with increased ERbeta expression and altered
      PR expression may promote luteolysis in the pig CL.

PMID- 14724133
TI  - The primate embryo gene expression resource: a novel resource to facilitate rapid
      analysis of gene expression patterns in non-human primate oocytes and
      preimplantation stage embryos.
AB  - Detailed molecular studies of preimplantation stage development in a suitable
      nonhuman primate model organism have been inhibited due to the cost and scarcity
      of embryos. To circumvent these limitations, we have created a new resource for
      the research community, designated as the Primate Embryo Gene Expression Resource
      (PREGER). The PREGER sample collection currently contains over 160 informative
      samples of oocytes, obtained from various sized antral follicles, and embryos
      obtained through a variety of different protocols. The PREGER makes it possible
      to undertake quantitative gene-expression studies in rhesus monkey oocytes and
      embryos through simple and cost-effective hybridization-based methods. The PREGER
      also makes available other molecular tools to facilitate nonhuman primate
      embryology. We used PREGER here to compare the temporal expression patterns of
      five housekeeping mRNAs and three transcription factor mRNAs between mouse and
      rhesus monkey. We observed noticeable differences in temporal expression patterns
      between species for some mRNAs, but clear similarities for others. Our results
      also provide new information related to genome activation and the effects of
      embryo culture conditions on gene expression in primate embryos. These results
      provide one illustration of how the PREGER can be employed to obtain novel
      insight into primate embryogenesis.

PMID- 14724134
TI  - Expression of genes encoding chromatin regulatory factors in developing rhesus
      monkey oocytes and preimplantation stage embryos: possible roles in genome
      activation.
AB  - One of the most critical events of preimplantation development is the successful
      activation of gene transcription. Both the timing and the array of genes
      activated must be controlled. The ability to regulate gene transcription appears
      to be reduced just prior to the time of the major genome activation event, and
      changes in chromatin structure appear essential for establishing this ability.
      Major molecules that modulate chromatin structure are the linker and core
      histones, enzymes that modify histones, and a wide variety of other factors that
      associate with DNA and mediate either repressive or activating changes. Among the
      latter are chromatin accessibility complexes, SWI/SNF complexes, and the YY1
      protein and its associated factors. Detailed information about the expression and
      regulation of these factors in preimplantation stage embryos has not been
      published for any species. In order to ascertain which of these factors may
      participate in chromatin remodeling, genome activation, and DNA replication
      during early primate embryogenesis, we determined the temporal expression
      patterns of mRNA encoding these factors. Our data identify the predominant
      members of these different functional classes of factors expressed in oocytes and
      embryos, and reveal patterns of expression distinct from those patterns seen in
      somatic cells. Among each of four classes of mRNAs examined, some mRNAs were
      expressed predominantly in the oocyte, with these largely giving way to others
      expressed stage specifically in the embryo. This transition may be part of a
      global mechanism underlying the transition from maternal to embryonic control of
      development, wherein the oocyte program is silenced and an embryonic pattern of
      gene expression becomes established. Possible roles for these mRNAs in chromatin
      remodeling, genome activation, DNA replication, cell lineage determination, and
      nuclear reprogramming are discussed.

PMID- 14724135
TI  - The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b-
      containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids.
AB  - Acrosome biogenesis involves the transport and fusion of Golgi-derived
      proacrosomal vesicles along the acroplaxome, an F-actin/keratin 5-containing
      cytoskeletal plate anchored to the spermatid nucleus. A significant issue is
      whether the acroplaxome develops in acrosomeless mutant mice. Male mice with a
      Hrb null mutation are infertile and both spermatids and sperm are round-headed
      and lack an acrosome. Hrb, a protein that contains several NPF motifs (Asn-Pro
      Phe) and interacts with proteins with Eps15 homology domains, is regarded as
      critical for the docking and/or fusion of Golgi-derived proacrosomal vesicles.
      Here we report that the lack of an acrosome in Hrb mutant spermatids does not
      prevent the development of the acroplaxome. Yet the acroplaxome in the mutant
      contains F-actin but is deficient in keratin 5. We also show that the actin-based
      motor protein myosin Va and its receptor, Rab27a/b, known to be involved in
      vesicle transport, are present in the Golgi and Golgi-derived proacrosomal
      vesicles in wild-type and Hrb mutant mouse spermatids. In the Hrb mutant, myosin
      Va-bound proacrosome vesicles tether to the acroplaxome, where they flatten and
      form a flat sac, designated pseudoacrosome. As spermiogenesis advances, round
      shaped spermatid nuclei of the mutant display several nuclear protrusions,
      designated nucleopodes. Nucleopodes are consistently found at the acroplaxome-
      pseudoacrosome site. Our findings support the interpretation that the acroplaxome
      provides a focal point for myosin-Va/ Rab27a/b-driven proacrosomal vesicles to
      accumulate, coalesce, and form an acrosome in wild-type spermatids and a
      pseudoacrosome in Hrb mutant spermatids. We suggest that nucleopodes develop at a
      site where a keratin 5-deficient acroplaxome may not withstand tension forces
      operating during spermatid nuclear shaping.

PMID- 14724136
TI  - Estradiol and its membrane-impermeable conjugate (estradiol-bovine serum albumin)
      during in vitro maturation of bovine oocytes: effects on nuclear and cytoplasmic
      maturation, cytoskeleton, and embryo quality.
AB  - In various cell types, there is increasing evidence for nongenomic steroid
      effects, i.e., effects that are not mediated via the classical steroid receptors.
      However, little is known about the involvement of the nongenomic pathway of
      estradiol (E2) on mammalian oocyte in vitro maturation (IVM). The aim of this
      study was to investigate whether the effects of E2 on bovine oocyte IVM are
      mediated via a plasma membrane receptor (nongenomic). First, we investigated the
      expression of estradiol (classical) receptor alpha (ERalpha) and beta (ERbeta)
      mRNA in oocytes and cumulus cells (CC). We also studied the effects of different
      exposure times to E2 (before and after germinal vesicle breakdown, GVBD) on
      nuclear maturation. To study the possible involvement of the putative estradiol
      plasma membrane receptor on the IVM of oocytes, we used E2 conjugated with bovine
      serum albumin (E2-BSA), which cannot cross the plasma membranes. Our results
      demonstrate that oocytes expressed ERbeta mRNA, while CC expressed both ERalpha
      and ERbeta mRNA. Exposure to E2 during the first 8 h of culture (before GVBD)
      induced a block at the metaphase I stage (MI). However, the presence of E2 after
      GVBD induced an increase of oocytes with nuclear aberrations. Meiotic spindle
      organization was severely affected by E2 during IVM and multipolar spindle was
      the most frequently observed aberration. Exposure of oocytes to E2-BSA did not
      affect nuclear maturation, blastocyst formation rate, nor embryo quality. Our
      results suggest that the detrimental effects of E2 on in vitro nuclear maturation
      of bovine oocyte are not exerted via a plasma membrane receptor.

PMID- 14724137
TI  - Rosbin: a novel homeobox-like protein gene expressed exclusively in round
      spermatids.
AB  - Mammalian spermiogenesis is a complex process occurring in a highly coordinated
      fashion within the seminiferous tubules. To elucidate the molecular mechanisms
      controlling haploid germ cell differentiation, we have isolated haploid germ cell
      specific cDNA clones from a subtracted cDNA library of mouse testis. One of
      these cDNAs, Rosbin, is 3.2 kilobases (kb) long and has an open reading frame of
      2385 nucleotides encoding a putative protein of 795 amino acid residues. A
      computer-mediated homology search revealed that it contained a domain similar to
      that of homeobox genes. Northern blot analysis revealed a 3.2-kb mRNA expressed
      exclusively in male germ cells. Transcription of the Rosbin gene was not observed
      in prepubertal testis but became detectable after Day 23. By Western blot
      analysis the protein encoded by this gene had a molecular mass of 89 kDa,
      expressing specifically in the testis and localized to the nucleus of stages IV
      VIII haploid round spermatids, predominantly at stages VII-VIII of
      spermatogenesis. ROSBIN is associated with and is most likely phosphorylated by
      protein kinase A. We suggest that it plays an important role in transcriptional
      regulation in haploid germ cells.

PMID- 14724138
TI  - Critical role of insulin-like growth factor system in follicle selection and
      dominance in mares.
AB  - The role of the insulin-like growth factor (IGF) system in the deviation in
      growth rates among follicles (follicle selection) was studied in mares using an
      IGF binding protein (BP) to reduce the follicular-fluid concentrations of IGFs.
      The future dominant follicle (F1) was treated by intrafollicular injection at the
      expected beginning of deviation (F1 > or = 20 mm; Day 0). The experimental groups
      were control (no injection, n = 8), vehicle (injection of vehicle; n = 6), and BP
      (injection of 250 microg of recombinant human IGFBP-3; n = 6). A sample of
      follicular fluid was taken from F1 on Day 1 in all groups. Compared with the
      control group, IGFBP-3 reduced (P < 0.05) the follicular-fluid concentration of
      free IGF-1 by 90%; lowered (P < 0.05) the concentrations of estradiol, activin-A,
      inhibin-A, and vascular endothelial growth factor; and increased (P < 0.05) the
      concentration of androstenedione. The diameter of F1 decreased and the diameter
      of F2 increased after Day 0 in the BP group, compared with the control and
      vehicle groups. A greater (P < 0.05) increase in circulating concentrations of
      FSH between Days 0 and 1 occurred in the BP group than in the other groups and
      accounted for the increased growth of F2. Dominance and ovulation from F1
      occurred from fewer (P < 0.03) mares in the BP group (1 of 6) than from the
      control and vehicle groups combined (11 of 14); the remaining mares in the BP
      group ovulated from F2. Results indicated that the IGF system has a critical
      intrafollicular role in the differential changes in concentrations of follicular
      fluid factors between the future dominant and subordinate follicles, leading to
      the development of follicle dominance (selection) and ovulation in mares.

PMID- 14724140
TI  - Endothelin and vascular function in liver disease.
AB  - The endothelins are a group of three related peptides with two receptor subtypes,
      ET(A) and ET(B). Following the discovery of endothelin 1 as a potent
      vasoconstrictor, there has been intense interest in the role of endothelin on
      vascular function in liver disease. Speculation on the role of endothelin in the
      pathogenesis of acute renal failure, including hepatorenal syndrome, has also
      been speculated.

PMID- 14724139
TI  - Guidelines on the use of oesophageal dilatation in clinical practice.

PMID- 14724141
TI  - Cerebral venous thrombosis in acute inflammatory bowel disease.

PMID- 14724142
TI  - Are we underestimating acid reflux?

PMID- 14724143
TI  - A snapshot of colonoscopy practice in England: stimulus for improvement.

PMID- 14724144
TI  - Surveillance colonoscopy in ulcerative colitis: magnifying chromoendoscopy in the
      spotlight.

PMID- 14724145
TI  - Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar
      junction: evidence of short segment reflux.
AB  - BACKGROUND AND AIMS: Oesophageal pH is conventionally recorded from a point 5 cm
      above the lower oesophageal sphincter. However, the mucosal changes of reflux
      oesophagitis and intestinal metaplasia tend to affect the segment of oesophagus
      distal to this and close to the squamocolumnar junction. This study set out to
      investigate oesophageal acid exposure of squamous mucosa close to the
      squamocolumnar junction. METHODS: Dual channel 24 hour pH monitoring was carried
      out in 11 patients with endoscopy negative dyspepsia and no evidence of gastro
      oesophageal reflux by conventional oesophageal pH metry. Oesophageal pH was
      recorded from electrodes positioned 5 mm and 55 mm proximal to the squamocolumnar
      junction. A novel technique was developed using metal clips to secure the pH
      catheter to the oesophageal mucosa and maintain these electrode positions.
      Oesophageal manometry indicated that the distal electrode was within the high
      pressure zone of the lower oesophageal sphincter. RESULTS: We found that 24 hour
      oesophageal acid exposure (per cent time pH <4) was greater 5 mm above the
      squamocolumnar junction compared with the conventional position 5 cm more
      proximal (11.7% v 1.8%; p<0.001). The greater acid exposure at the distal versus
      the conventional site was apparent in both the upright (12.7% v 2.3%) and supine
      (10.5% v 1.3%) positions, as well as during preprandial (14.2% v 1.6%) and
      postprandial (21.8% v 2.8%) periods (p<0.001 for each). The number of reflux
      events recorded close to the squamocolumnar junction was also higher than at the
      conventional position (168 v 33; p<0.001). There was no correlation between acid
      exposure at the two sites. CONCLUSIONS: The squamous mucosa of the most distal
      oesophagus is exposed to substantial acidic reflux, even in patients without
      evidence of conventional reflux disease. This short segment reflux may explain
      the high incidence of metaplasia and neoplasia at the gastro-oesophageal
      junction.

PMID- 14724146
TI  - Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal
      reflux disease: a double blind, placebo controlled, randomised trial.
AB  - BACKGROUND: The role of Helicobacter pylori eradication in the management of
      gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H
      pylori eradication leads to worsened control of reflux disease. METHODS:
      Consecutive patients with weekly reflux symptoms were prospectively recruited for
      endoscopy and symptom evaluation. Patients were enrolled if they had H pylori
      infection and required long term acid suppressants. Eligible patients were
      randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with
      placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given
      for eight weeks for healing of oesophagitis and symptom relief. This was followed
      by a maintenance dose of 10 mg daily for up to 12 months. The primary study end
      point was the probability of treatment failure within 12 months, which was
      defined as either incomplete resolution of symptoms or oesophagitis at the
      initial treatment phase, or relapse of symptoms and oesophagitis during the
      maintenance phase. Predictors of treatment failure were determined by Cox's
      proportional hazards model. RESULTS: A total of 236 GORD patients were screened
      and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in
      the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group).
      Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was
      eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15
      patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had
      treatment failure. The 12 month probability of treatment failure was 43.2% (95%
      confidence interval (CI) 29.9-56.5%) in the HpE group and 21.1% (95% CI 9.9
      32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional
      hazards model, after adjustment for the covariates age, sex, erosive
      oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at
      baseline, H pylori eradication was the only predictor of treatment failure
      (adjusted hazard ratio 2.47 (95% CI 1.05-5.85)). CONCLUSION: H pylori eradication
      leads to more resilient GORD.

PMID- 14724147
TI  - Effect of childhood adversity on health related quality of life in patients with
      upper abdominal or chest pain.
AB  - BACKGROUND AND AIMS: This study assessed whether childhood and current
      adversities: (a) were more prevalent in patients with functional dyspepsia (FD)
      or non-cardiac chest pain (NCCP) than in patients with gastro-oesophageal reflux
      disease (GORD) or ischaemic heart disease (IHD); and (b) predicted health related
      quality of life in these disorders. PATIENTS: Cohort study of consecutive
      attenders to gastroenterology and cardiology clinics in a secondary/tertiary
      referral centre. METHODS: Patients were interviewed using the childhood
      experience of care and abuse and life events and difficulties schedules. Distress
      was assessed by questionnaire. Outcome was assessed using SF36 at the index
      clinic visit and six months later. RESULTS: A total of 133 patients were included
      (40 NCCP, 43 FD, 29 GORD, and 21 IHD) (67% response rate). The diagnostic groups
      did not differ significantly in the proportion reporting childhood adversity
      (30%), ongoing social stress (40%), lack of a close confidant (14%), or level of
      psychological distress. Reported childhood adversity was associated with poor
      outcome at the index visit (SF36 physical component score: 36.6 (SEM 1.8) v 42.3
      (SEM 1.2) for the remainder; p = 0.014). In multiple regression analysis,
      childhood adversity was a significant independent predictor for patients with
      functional disorders (NCCP and FD) but not organic disorders (GORD or IHD).
      Change in SF36 score at six months was determined by age and distress score at
      the index visit in both groups. CONCLUSION: Childhood adversity was common among
      this consecutive sample but was associated directly with poor outcome only in
      patients with functional gastrointestinal syndromes. Distress is an important
      predictor of outcome in all patients. Greatest impairment occurs when lack of
      social support accompanies reported childhood adversity.

PMID- 14724148
TI  - Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in
      Mongolian gerbils.
AB  - BACKGROUND: and aim: Although ghrelin, a novel growth hormone releasing peptide
      localised mainly in the gastric fundus, is reported not only to accelerate food
      passage and gastrointestinal motility but also to affect appetite and weight
      control, regulation of gastric ghrelin secretion under the conditions of gastric
      Helicobacter pylori infection is unknown. The present study was designed to
      investigate plasma and gastric ghrelin levels in Mongolian gerbils with H pylori
      colonisation of the gastric mucosa. METHODS: Gerbils orally inoculated with H
      pylori were examined after inoculation. To examine preproghrelin mRNA expression
      in the gastric mucosa, cDNA encoding the gerbil preproghrelin and glyceraldehyde
      3-phosphate dehydrogenase homologue was isolated and a quantitative reverse
      transcription-polymerase chain reaction system was established. RESULTS: In
      gerbils showing H pylori colonisation (H pylori group), expression of
      preproghrelin mRNA and total ghrelin levels were significantly decreased 17 and
      23 weeks later (p<0.01). Although the number of ghrelin immunoreactive cells
      decreased as the stomach weight increased, the gastric contents of total and
      active ghrelin in this group were the same as those in controls. Gastric
      myeloperoxidase activity showed a positive correlation with plasma ghrelin
      levels. On the other hand, at 17 weeks, plasma ghrelin levels were significantly
      increased in the H pylori group (p<0.05), suggesting a compensatory increase in
      secretion of the peptide at this time point. CONCLUSION: The present experimental
      study demonstrated that gastric and plasma ghrelin dynamics are altered in
      response to H pylori infection.

PMID- 14724149
TI  - Chemoprevention of gastric cancer by celecoxib in rats.
AB  - BACKGROUND: Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in
      gastric cancer and is believed to play a crucial role in gastric carcinogenesis.
      AIM: We examined the chemopreventive effect of a COX-2 inhibitor in an animal
      model of stomach carcinogenesis. METHODS: Eighty six male Wistar rats were
      divided into six different treatment groups: group A, water alone (n = 5); group
      B, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG 100 micro g/ml) (n = 16); group C,
      indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17);
      group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day)
      (n = 16). Group B-F animals were treated with 10% sodium chloride (in the initial
      six weeks) and MNNG in drinking water to induce adenocarcinoma in the stomach.
      All animals received treatment for 40 weeks, and were sacrificed after death or
      at 48 weeks. Gastric neoplasm was evaluated by histology. RESULTS: The incidences
      of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in
      group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with
      MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour
      multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume
      (2.4 v 2805 mm(3); p = 0.02). Although tumours had significantly higher COX-2
      expression than their adjacent normal tissues (p<0.02), there was no significant
      difference in COX-2 levels among tumours in the different treatment groups. The
      lowest tumour prostaglandin E(2) level was found in the indomethacin treated
      group, suggesting that the chemopreventive effect of celecoxib may be mediated by
      a COX independent pathway. CONCLUSION: While treatment with indomethacin had no
      significant effect on tumour development, treatment with celecoxib reduced
      gastric cancer incidence and growth in rats.

PMID- 14724150
TI  - Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral
      intestinal iron transport, in the sex linked anaemia mouse.
AB  - BACKGROUND: Hephaestin is a multicopper ferroxidase required for basolateral
      transport of iron from enterocytes. Sex linked anaemia (sla) mice have a defect
      in the release of iron from intestinal enterocytes into the circulation due to an
      interstitial deletion in the hephaestin gene (heph). RESULTS: We have
      demonstrated that hephaestin is primarily localised to a supranuclear compartment
      in both intestinal enterocytes and in cultured cells. In normal intestinal
      enterocytes, hephaestin was also present on the basolateral surface. In sla mice,
      hephaestin was present only in the supranuclear compartment. In contrast, the
      iron permease Ireg1 localised to the basolateral membrane in both control and sla
      mice. CONCLUSION: We suggest that mislocalisation of hephaestin likely
      contributes to the functional defect in sla intestinal epithelium.

PMID- 14724152
TI  - The role of platelet activating factor in a neonatal piglet model of necrotising
      enterocolitis.
AB  - BACKGROUND AND AIMS: Necrotising enterocolitis (NEC) is a potentially devastating
      disorder of preterm infants but its aetiology remains unclear. The aim of these
      studies was to develop a neonatal piglet model for NEC and to then use the model
      to investigate the role of platelet activating factor (PAF) in its pathogenesis.
      METHODS: Anaesthetised newborn piglets were divided into six groups: (i)
      controls, and groups subjected to (ii) hypoxia, (iii) lipopolysaccharide (LPS),
      (iv) hypoxia+LPS, (v) hypoxia+LPS and the PAF antagonist WEB 2170, and (vi) PAF.
      Arterial blood pressure (ABP), superior mesenteric artery blood flow (MBF),
      mesenteric vascular conductance (MVC), and arterial blood gases were recorded,
      and intestinal histology was evaluated. RESULTS: Exposure to LPS, hypoxia+LPS, or
      PAF all caused haemorrhagic intestinal lesions associated with varying degrees of
      intestinal injury. PAF caused a significant initial decrease in both MVC and MBF
      whereas hypoxia+LPS caused a significant late reduction in ABP and MBF with a
      trend towards a decrease in MVC. The effects of hypoxia+LPS on both haemodynamic
      changes and intestinal injury were ameliorated by WEB 2170. CONCLUSIONS:
      Administration of hypoxia and LPS or of PAF in the neonatal piglet induces
      haemodynamic changes and intestinal lesions that are consistent with NEC. These
      effects are ameliorated by prior administration of WEB 2170, indicating an
      important role for PAF in the pathogenesis of NEC.

PMID- 14724153
TI  - Nitric oxide inhibitable isoforms of adenylate cyclase mediate epithelial
      secretory dysfunction following exposure to ionising radiation.
AB  - BACKGROUND: Hyporesponsiveness of the intestinal epithelium to secretagogues
      occurs in different models of intestinal injury, including radiation enteropathy,
      and in human disease. While this impairment of barrier function has been linked
      to increased inducible nitric oxide synthase (iNOS) activity, the cellular target
      of NO in this phenomenon is not known, although recent studies suggest that some
      isoforms of adenylate cyclase are inhibited by NO. AIMS: To determine adenylate
      cyclase isoform distribution in colonic epithelial cells and, in particular, the
      physiological significance of NO inhibitable adenylate cyclase isoforms 5 and 6
      in radiation induced epithelial secretory dysfunction. METHODS: Reverse
      transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and
      immunohistochemistry were used to examine adenylate cyclase expression. The
      responsiveness of mouse colon to secretagogues 72 hours post-15 Gy gamma
      radiation or following in vitro exposure to NO donors was measured in Ussing
      chambers. Also, cAMP, cGMP, and ATP levels were measured. RESULTS: RT-PCR,
      immunocytochemistry, and immunohistochemistry showed that adenylate cyclase 5 was
      expressed in mouse colon, and isoforms 5 and 6 were expressed in human biopsies
      and intestinal epithelium. Pharmacological studies showed that these isoforms are
      functionally important in chloride secretion. NO mediated hyporesponsiveness to
      secretagogues is primarily a result of decreased adenylate cyclase activity, and
      not G(i) activation or decreased cellular ATP levels. CONCLUSIONS: NO inhibitable
      isoforms of adenylate cyclase are expressed in mouse and human secretory colonic
      epithelia, and appear to be the target of radiation induced NO to reduce the
      responsiveness to cAMP dependent secretagogues.

PMID- 14724154
TI  - Proinflammatory cytokines increase glial fibrillary acidic protein expression in
      enteric glia.
AB  - BACKGROUND: Enteric glia protect the integrity of the gut, as loss of enteric
      glial fibrillary acidic protein (GFAP) positive (+) glia leads to a haemorrhagic
      jejunoileitis. Crohn's disease (CD) and necrotising enterocolitis (NEC) show
      pathological changes in enteric glia. Therefore, factors controlling GFAP+
      enteric glia are of great interest. The aim of the present study was to
      characterise enteric glia and determine the effect of interleukin 1beta (IL
      1beta), interleukin 4 (IL-4), tumour necrosis factor alpha (TNF-alpha), and
      lipopolysaccharides (LPS) on cultured enteric glia. METHODS: Dissected rat colon
      and cultured enteric glia cells were double labelled with anti-GFAP and anti-S
      100 antibodies. For regulatory studies, enteric glia cells were treated with
      cytokines and LPS. Proliferation was assayed using bromodeoxyuridine (BrdU) and
      mitosis of enteric glia was blocked by demecolcine. RESULTS: We were able to
      distinguish GFAP negative (-) from GFAP+ glia subtypes in situ and in primary
      cultures. Incubation of cells with IL-1beta, TNF-alpha, and LPS led to a
      significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP
      expression. After incubation with IL-1beta, total intracellular GFAP of enteric
      glia cells was increased. Upregulation of GFAP+ enteric glia could also be
      observed after stimulation with IL-1beta on blocking mitosis. BrdU uptake in
      stimulated enteric glia showed no increased proliferation rate. CONCLUSIONS: Two
      different types of enteric glia based on GFAP expression exist in the gut.
      Proinflammatory cytokines and LPS cause a dramatic increase in GFAP+ enteric
      glia. This suggests that cytokines play an important role in controlling GFAP+
      enteric glia which might in turn be involved in modulating the integrity of the
      bowel during inflammation.

PMID- 14724155
TI  - Evidence for the presence of functional protease activated receptor 4 (PAR4) in
      the rat colon.
AB  - BACKGROUND AND AIMS: Protease activated receptors (PARs) have been postulated to
      play a role during intestinal inflammation. The presence and role played by
      PAR(4) in gastrointestinal functions have not been fully clarified. The aims of
      this study were: (i) to examine expression of PAR(4) in rat proximal colon; (ii)
      to determine the mechanical effects induced by PAR(4) activation in longitudinal
      muscle; and (iii) to characterise the underlying mechanisms. METHODS: PAR(4)
      expression was determined by reverse transcription-polymerase chain reaction (RT
      PCR) and immunohistochemistry. Mechanical activity was recorded as changes in
      isometric tension. RESULTS: A PCR product corresponding to the predicted size of
      the PAR(4) signal was amplified from RNA prepared from the colon of rats, showing
      the presence of PAR(4) in those tissues. Immunohistochemistry revealed that
      PAR(4) protein was expressed on epithelial surfaces and submucosa. PAR(4)
      activating peptides, GYPGKF-NH(2) and AYPGKG-NH(2), produced concentration
      dependent contractile effects on longitudinal muscle. Tetrodotoxin (TTX) or
      atropine significantly reduced the contractile responses to AYPGKG-NH(2), and
      atropine after TTX did not cause any further reduction. NK(1) receptor
      antagonist, SR140333, or NK(2) receptor antagonist, SR48968, alone or in
      combination, produced a reduction in PAR(4) induced contractile effect, and when
      coadministered with TTX abolished it. Capsaicin markedly reduced the contractions
      evoked by AYPGKG-NH(2). CONCLUSIONS: The present results suggest that PAR(4) is
      functionally expressed in rat colon and its activation induces contraction of the
      longitudinal muscle both through TTX sensitive release of acetylcholine and
      release of tachykinins, probably from sensory nerves. These actions may
      contribute to motility disturbances during intestinal trauma and inflammation.

PMID- 14724156
TI  - Molecular targets for tumour progression in gastrointestinal stromal tumours.
AB  - BACKGROUND AND AIMS: The distinction between benign and malignant
      gastrointestinal stromal tumours (GISTs) is often unclear at the clinical and
      histopathology levels. GISTs are believed to arise from the stem cells of Cajal.
      In order to define genetic biomarkers and identify target genes related to GIST
      progression, we analysed and compared benign and malignant GISTs with verified
      follow up data using cDNA expression arrays. METHODS: Eight genes were frequently
      overexpressed in malignant GISTs and their overexpression was confirmed using
      quantitative real time reverse transcription-polymerase chain reaction. These
      genes included ezrin (villin 2 (VIL2)), collagen 8 alpha 1 subunit (COL8A1),
      G2/mitotic specific cyclin B1 (CCNB1), high mobility group protein (HMG2), TSG101
      tumour susceptibility protein, CENP-F kinetochore protein, protein tyrosine
      kinase 2 (FAK), and protein kinase DYRK2. To test these genes in a clinical
      setting, we obtained diagnostic samples of 16 additional GISTs that were
      classified at diagnosis as benign, malignant, and uncertain malignant potential
      (UMP). RESULTS: There was remarkable gene overexpression in all malignant GISTs.
      Statistical analyses revealed significant correlations between overexpression of
      several gene pairs in malignant GISTs. We found the strongest correlations
      (rho>0.70) among the significant correlations (p<0.01) between CCNB1-CENP-F (rho
      = 0.87) and CCNB1-FAK (rho = 0.73). Gene expression of the UMP GISTs suggested
      two different groups. Three UMP GISTs had gene expression consistent with
      malignant tumours and their follow up data revealed that indeed these patients
      had recurrences later on. On the other hand, UMP GISTs that had low gene
      expression levels continued free of disease for several years. CONCLUSIONS: These
      results provide insight into the oncogenesis of GISTs and suggest that testing
      the expression profile of a number of genes may segregate GISTs into groups of
      different tumour behaviour.

PMID- 14724157
TI  - Randomised clinical trial of synbiotic therapy in elective surgical patients.
AB  - BACKGROUND: It is possible to manipulate the composition of the gastrointestinal
      microflora by administration of pre- and probiotics. This may help to preserve
      gut barrier function and reduce the incidence of septic morbidity. AIMS: To
      assess the effects of a combination of pre- and probiotics (synbiotic) on
      bacterial translocation, gastric colonisation, systemic inflammation, and septic
      morbidity in elective surgical patients. PATIENTS: Patients were enrolled two
      weeks prior to elective abdominal surgery. Seventy two patients were randomised
      to the synbiotic group and 65 to the placebo group. Patients were well matched
      regarding age and sex distribution, diagnoses, and POSSUM scores. METHODS:
      Patients in the synbiotic group received a two week preoperative course of
      Lactobacillus acidophilus La5, Bifidobacterium lactis Bb-12, Streptococcus
      thermophilus, and Lactobacillus bulgaricus, together with the prebiotic
      oligofructose. Patients in the placebo group received placebo capsules and
      sucrose powder. At surgery, a nasogastric aspirate, mesenteric lymph node, and
      scrapings of the terminal ileum were harvested for microbiological analysis.
      Serum was collected preoperatively and on postoperative days 1 and 7 for
      measurement of C reactive protein, interleukin 6, and antiendotoxin antibodies.
      Septic morbidity and mortality were recorded. RESULTS: There were no significant
      differences between the synbiotic and control groups in bacterial translocation
      (12.1% v 10.7%; p = 0.808, chi(2)), gastric colonisation (41% v 44%; p = 0.719),
      systemic inflammation, or septic complications (32% v 31%; p = 0.882).
      CONCLUSIONS: In this study, synbiotics had no measurable effect on gut barrier
      function in elective surgical patients. Further studies investigating the place
      of pre- and probiotics in clinical practice are required.

PMID- 14724158
TI  - Antibiotic use and the development of Crohn's disease.
AB  - BACKGROUND: Few environmental determinants of Crohn's disease are well
      established. Some observational data exist to implicate antibiotic use as a risk
      factor but these are derived from studies using questionnaires to assess reported
      antibiotic use that were susceptible to recall bias. We have therefore explored
      this relationship in prospectively gathered data. METHODS: We selected incident
      cases of Crohn's disease from the General Practice Research Database with at
      least five years of data prior to diagnosis. Controls with five years of complete
      data were randomly selected. Data were extracted on smoking, drug prescriptions,
      age, sex, and a variety of symptoms and diagnoses that might be indicative of
      occult Crohn's disease. Logistic regression was used to investigate the
      relationship between antibiotic use and Crohn's disease. RESULTS: A total of 587
      Crohn's disease cases and 1460 controls were available for analysis. We found
      that antibiotic use 2-5 years pre-diagnosis occurred in 71% of cases compared
      with 58% of controls (p<0.001), and the median number of courses was two in the
      cases and one in the controls (p<0.001). Adjusting for age, sex, smoking, and use
      of other drugs, antibiotic use had an odds ratio of 1.32 (1.05-1.65). We were
      unable to show specificity to any subgroup of antibacterials. Associations
      similar to that with antibiotics were also found with oral contraceptive,
      cardiovascular, and neurological drugs. CONCLUSIONS: We found a statistically
      significant association between Crohn's disease and prior antibiotic use. This
      cannot be explained by recall bias, but due to lack of specificity it is unclear
      whether it is causal.

PMID- 14724159
TI  - Hip fractures in patients with inflammatory bowel disease and their relationship
      to corticosteroid use: a population based cohort study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is known to be associated with
      reduced bone density but the extent to which this results in an increased risk of
      fracture and the contribution of corticosteroid therapy are unclear. We have
      conducted a large cohort study to address these issues. METHODS: We selected
      subjects within the General Practice Research Database (GPRD) with a diagnosis of
      IBD and up to five matched controls for each patient. We derived dates of
      recorded hip fractures and also information on smoking, use of corticosteroids,
      and a number of other drugs. We calculated the absolute risk of fracture and the
      relative risk as a hazard ratio corrected for available confounders by Cox
      regression. RESULTS: Seventy two hip fractures were recorded in 16 550 IBD cases
      and 223 in 82 917 controls. Cox modelling gave an unadjusted relative risk of hip
      fracture of 1.62 (95% confidence interval (CI) 1.24-2.11) for all IBD, 1.49 (1.04
      2.15) for ulcerative colitis (UC) and 2.08 (1.36-3.18) for Crohn's disease (CD).
      Multivariate modelling showed that both current and cumulative use of
      corticosteroids and use of opioid analgesics confounded this relationship. After
      adjusting for confounding, the relative risk was 1.41 (0.94-2.11) for UC and 1.68
      (1.01-2.78) for CD. CONCLUSION: The risk of hip fracture is increased
      approximately 60% in IBD patients. Corticosteroid use is a contributor to this,
      both in the long term as previously recognised and also in an acute reversible
      manner. The majority of hip fracture risk in IBD patients however cannot be
      attributed to steroid use.

PMID- 14724161
TI  - Sporadic duodenal adenoma is associated with colorectal neoplasia.
AB  - OBJECTIVE: The objective of this study was to assess the association between
      colorectal neoplasia and sporadic duodenal adenoma. METHODS: A retrospective case
      control study was conducted using the databases of two major teaching hospitals
      in Western Australia. The frequency of colorectal neoplasia in patients with
      sporadic duodenal adenomas was compared with that in a control group of patients
      presenting for endoscopies. The frequency of colorectal cancer in duodenal
      adenoma patients was also compared with the population incidence. RESULTS: Of 56
      sporadic duodenal adenoma patients, 34 (61%) had been colonoscoped. When
      comparing the findings between patients with sporadic duodenal adenoma and an
      endoscoped control group, all colorectal neoplasias were significantly more
      common in the duodenal adenoma group (56% v 33%; odds ratio (OR) 2.4 (95%
      confidence intervals (CI) 1.1-5.4)). Although finding either advanced colorectal
      adenoma or cancer was also more common in duodenal adenoma patients (38% v 19%;
      OR 2.3 (95% CI 1.0-5.2)), as was finding colorectal cancer alone (21% v 8%; OR
      3.0 (95% CI 1.0-9.1)), the results were not statistically significant. However,
      the incidence of colorectal cancer was much greater in duodenal adenoma patients
      than in the population (p<0.001). CONCLUSIONS: Sporadic duodenal adenoma has a
      clinically important association with colorectal neoplasia. Thus patients with
      duodenal adenomas should undergo colonoscopy to detect colorectal neoplasia.

PMID- 14724160
TI  - Pancolonic indigo carmine dye spraying for the detection of dysplasia in
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding
      extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies.
      Chromoendoscopy can aid detection of subtle mucosal abnormalities. We
      hypothesised that routine pancolonic indigo carmine dye spraying would improve
      the macroscopic detection of dysplasia and reduce the dependence on non-targeted
      biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive
      ulcerative colitis attending for colonoscopic surveillance underwent "back to
      back" colonoscopies. During the first examination, visible abnormalities were
      biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic
      indigo carmine (0.1%) was used during the second colonoscopic examination, and
      any additional visible abnormalities were biopsied. RESULTS: Median extubation
      times for the first and second colonoscopies were 11 and 10 minutes,
      respectively. The non-targeted biopsy protocol detected no dysplasia in 2904
      biopsies. Forty three mucosal abnormalities (20 patients) were detected during
      the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both
      were considered to be dysplasia associated lesions/masses. A total of 114
      additional abnormalities (55 patients) were detected following dye spraying, of
      which seven (five patients) were dysplastic: all were considered to be adenomas.
      There was a strong trend towards statistically increased dysplasia detection
      following dye spraying (p = 0.06, paired exact test). The targeted biopsy
      protocol detected dysplasia in significantly more patients than the non-targeted
      protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in
      2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with
      pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine
      dysplastic lesions, seven of which were only visible after indigo carmine
      application. Careful mucosal examination aided by pancolonic chromoendoscopy and
      targeted biopsies of suspicious lesions may be a more effective surveillance
      methodology than taking multiple non-targeted biopsies.

PMID- 14724162
TI  - Familial adenomatous polyposis patients without an identified APC germline
      mutation have a severe phenotype.
AB  - BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the
      dominantly inherited autosomal disease familial adenomatous polyposis (FAP).
      Germline mutations can be identified in the adenomatous polyposis coli (APC) gene
      in approximately 80% of patients. The APC protein comprises several regions and
      domains for interaction with other proteins, and specific clinical manifestations
      are associated with the mutation assignment to one of these regions or domains.
      AIMS: The phenotype in patients without an identified causative APC mutation was
      compared with the phenotype in patients with a known APC mutation and with the
      phenotypes characteristic of patients with mutations in specific APC regions and
      domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70
      different families were extracted from the Danish Polyposis register. METHODS:
      Differences in 16 clinical manifestations were analysed according to the
      patient's mutational status. Two sided independent t sample test, two sided
      chi(2) test, and odds ratios were calculated. RESULTS: Patients without
      identified APC mutations had a unique and severe phenotype, which was roughly
      described as: young age at diagnosis and subsequent death in spite of development
      of few colorectal adenomas; low risk of involvement of the upper gastrointestinal
      tract, as reflected by a low mean Spigelman stage, and a low risk of fundic gland
      polyposis. Finally, they had significantly fewer affected family members,
      although they do not themselves more often represent an isolated case.
      CONCLUSIONS: The severe phenotype should be considered when counselling FAP
      families in which attenuated FAP is excluded and in which a causative APC
      mutation has not been identified.

PMID- 14724163
TI  - Analysis of candidate modifier loci for the severity of colonic familial
      adenomatous polyposis, with evidence for the importance of the N-acetyl
      transferases.
AB  - BACKGROUND: We have recently shown that the severity of human colonic familial
      adenomatous polyposis (FAP) varies in a manner consistent with the action of
      modifier genes. These modifier genes may harbour common alleles which increase
      the risk of colorectal cancer (CRC) in the general population. Analyses have
      suggested several common polymorphisms as risk alleles for CRC. METHODS: We
      determined the association between the severity of colonic FAP (151 patients) and
      polymorphisms in MTHFR, NAT1, NAT2, GSTM, GSTT, cyclin D1, E-cadherin, and APC.
      All of these loci have been suggested as influencing the risk of CRC. Colonic FAP
      severity was quantitated as the number of polyps per colectomy specimen,
      standardised for colon size. We analysed the relationship between disease
      severity and genotype at the polymorphic site, making allowance for the position
      of the germline APC mutation. RESULTS: We identified significant associations
      between more severe disease and the absence of the NAT1*10 genotype in the whole
      group of patients. In a subset of patients with germline mutations in the so
      called "mutation cluster region", there was an association between more severe
      disease and the presence of NAT2*fast alleles. In the whole patient set, a
      relatively strong association existed between more severe disease and possession
      of both the NAT1*non-10 and NAT2*fast genotypes. There was weak evidence for an
      association between the APCT1493C allele and more severe disease in the whole
      patient group. No consistent association with disease severity was found for the
      other polymorphisms. CONCLUSION: The severity of colonic FAP may be modified by
      alleles at the NAT1 and/or NAT2 loci. The identity of any functional variation
      remains unknown as NAT1*10 appears to be non-functional and there is linkage
      disequilibrium between alleles at multiple sites within these loci which are
      adjacent on chromosome 8p22. While evidence from this study cannot be conclusive,
      our data suggest that NAT1 and NAT2 variants may explain an approximately twofold
      increase in polyp number in the FAP colon.

PMID- 14724164
TI  - A prospective study of colonoscopy practice in the UK today: are we adequately
      prepared for national colorectal cancer screening tomorrow?
AB  - AIM: To study the availability and quality of adult and paediatric colonoscopy in
      three National Health Service (NHS) regions. METHOD: A prospective four month
      study of colonoscopies in North East Thames, West Midlands, and East Anglia.
      PATIENTS: Subjects undergoing colonoscopy in 68 endoscopy units. RESULTS: A total
      of 9223 colonoscopies were studied. The mean number of colonoscopies performed
      over the four month period was 142 in district general hospitals and 213 in
      teaching hospitals. Intravenous sedation was administered in 94.6% of procedures,
      but 2.2% and 11.4% of "at risk" patients did not have continuous venous access or
      did not receive supplemental oxygen, respectively. Caecal intubation was recorded
      in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%.
      Reasons for failing to reach the caecum included patient discomfort (34.7%),
      looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was
      reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by
      diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9%
      and carcinoma in 3.8%. Only half of the patients remembered being told of
      possible adverse events prior to the procedure. Rectal bleeding requiring
      admission following colonoscopy was reported in six patients. The overall
      perforation rate was 1:769 and colonoscopy was considered a possible factor in
      six deaths occurring within 30 days of the procedure. Only 17.0% of
      colonoscopists had received supervised training for their first 100 colonoscopies
      and only 39.3% had attended a training course. CONCLUSION: There is serious under
      provision of colonoscopy service in most NHS hospitals. Endoscopy sedation
      guidelines are not always adhered to and there is a wide variation in practice
      between units. Colonoscopy is often incomplete and does not achieve the target
      90% caecal intubation rate. Serious complications of colonoscopy were comparable
      with previous studies. Training in colonoscopy is often inadequate and improved
      practice should result from better training.

PMID- 14724166
TI  - Accuracy of reporting of family history of colorectal cancer.
AB  - BACKGROUND AND AIMS: Family history is used extensively to estimate the risk of
      colorectal cancer but there is considerable potential for recall bias and
      inaccuracy. Hence we systematically assessed the accuracy of family history
      reported at interview compared with actual cancer experience in relatives.
      METHODS: Using face to face interviews, we recorded family history from 199
      colorectal cancer cases and 133 community controls, totalling 5637 first and
      second degree relatives (FDRs/SDRs). We linked computerised cancer registry data
      to interview information to determine the accuracy of family history reporting.
      RESULTS: Cases substantially underreported colorectal cancer arising both in FDRs
      (sensitivity 0.566 (95% confidence interval (CI) 0.433, 0.690); specificity 0.990
      (95% CI 0.983, 0.994)) and SDRs (sensitivity 0.271 (95% CI 0.166, 0.410);
      specificity 0.996 (95% CI 0.992, 0.998)). There was no observable difference in
      accuracy of reporting family history between case and control interviewees.
      Control subjects similarly underreported colorectal cancer in FDRs (sensitivity
      0.529 (95% CI 0.310, 0.738); specificity 0.995 (95% CI 0.989, 0.998)) and SDRs
      (sensitivity 0.333 (95% CI 0.192, 0.512); specificity 0.995 (95% CI 0.991,
      0.995)). To determine practical implications of inaccurate family history, we
      applied family history criteria before and after record linkage. Only two of five
      families reported at interview to meet surveillance criteria did so after
      validation, whereas only two of six families that actually merited surveillance
      were identified by interview. CONCLUSIONS: This study has quantified the
      inaccuracy of interview in identifying people at risk of colorectal cancer due to
      a family history. Colorectal cancer was substantially underreported and so family
      history information should be interpreted with caution. These findings have
      considerable relevance to identifying patients who merit surveillance colonoscopy
      and to epidemiological studies.

PMID- 14724165
TI  - Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of
      neoplasia in flat and depressed lesions of the colorectum: a prospective
      analysis.
AB  - BACKGROUND: High magnification chromoscopic colonoscopy (HMCC) permits the in
      vivo examination of the colorectal pit pattern, which has a high correlation with
      stereomicroscopic appearances of resected specimens. This new technology may
      provide an "optical biopsy" which can be used to aid diagnostic precision and
      guide therapeutic strategies. Conflicting data exist concerning the accuracy of
      this technique when discriminating neoplastic from non-neoplastic lesions,
      particularly when flat and depressed. AIM: To prospectively examine the efficacy
      of HMCC for the diagnosis of neoplasia in flat and depressed colorectal lesions
      using standardised morphological, pit pattern, and histopathological criteria.
      Clinical recommendations for the use of HMCC are made. METHODS: Total colonoscopy
      was performed on 1850 patients by a single endoscopist from January 2001 to July
      2003 using the C240Z magnifying colonoscope. Identified lesions were classed
      according to the Japanese Research Society guidelines, and pit pattern according
      to Kudos modified criteria. Pit pattern appearances were then compared with
      histopathology. RESULTS: A total of 1008 flat lesions were identified. The
      sensitivity and specificity of HMCC in distinguishing non-neoplastic from
      neoplastic lesions were 98% and 92%, respectively. However, when using HMCC to
      differentiate neoplastic/non-invasive from neoplastic/invasive lesions,
      sensitivity was poor (50%) with a specificity of 98%. Diagnostic accuracy was not
      influenced by size or morphological classification of lesions. CONCLUSION: HMCC
      has a high overall accuracy at discriminating neoplastic from non-neoplastic
      lesions but is not 100% accurate. HMCC is a useful diagnostic tool in vivo but
      presently is not a replacement for histology. Requirements for further education
      and training in these techniques need to be addressed.

PMID- 14724167
TI  - Management of infectious diarrhoea.

PMID- 14724169
TI  - Antagonist: Early surgical intervention in ulcerative colitis.

PMID- 14724168
TI  - Protagonist: Early surgical intervention in ulcerative colitis.

PMID- 14724170
TI  - Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal
      reflux disease.
AB  - The important issue of whether Heliobacter pylori eradication leads to increased
      reflux has been the subject of many apparently contradictory publications, but
      when we asked two leading authorities to give us their views, there turned out to
      be considerable consensus, as you can read below.

PMID- 14724171
TI  - Helicobacter pylori eradication does not exacerbate gastro-oesophageal reflux
      disease.
AB  - The reciprocal influence of Helicobacter pylori infection and gastro-oesophageal
      reflux disease (GORD), if both conditions occur concomitantly, has been an issue
      of debate for many years. The critical question is whether eradication of H
      pylori has a more beneficial, harmful, or simply no effect on the course of GORD.

PMID- 14724173
TI  - Helicobacter pylori, ghrelin, and obesity.

PMID- 14724174
TI  - Ghrelin and Helicobacter pylori.

PMID- 14724175
TI  - The generation of antibody diversity through somatic hypermutation and class
      switch recombination.

PMID- 14724176
TI  - Calorie restriction extends yeast life span by lowering the level of NADH.
AB  - Calorie restriction (CR) extends life span in a wide variety of species.
      Previously, we showed that calorie restriction increases the replicative life
      span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase.
      Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by
      regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR
      decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A
      genetic intervention that specifically decreases NADH levels increases life span,
      validating the model that NADH regulates yeast longevity in response to CR.

PMID- 14724177
TI  - NF-kappaB RelA opposes epidermal proliferation driven by TNFR1 and JNK.
AB  - NF-kappaB inhibition promotes epidermal tumorigenesis; however, whether this
      reflects an underlying role in homeostasis or a special case confined to
      neoplasia is unknown. Embryonic lethality of mice lacking NF-kappaB RelA has
      hindered efforts to address this. We therefore generated developmentally mature
      RelA(-/-) skin. RelA(-/-) epidermis displays hyperplasia without abnormal
      differentiation, inflammation, or apoptosis. Hyperproliferation is TNFR1
      dependent because Tnfr1 deletion normalized cell division. TNFR1-dependent JNK
      activation occurred in RelA(-/-) epidermis, and JNK inhibition abolished
      hyperproliferation due to RelA deficiency. Thus, RelA antagonizes TNFR1-JNK
      proliferative signals in epidermis and plays a nonredundant role in restraining
      epidermal growth.

PMID- 14724178
TI  - Progesterone and insulin stimulation of CPEB-dependent polyadenylation is
      regulated by Aurora A and glycogen synthase kinase-3.
AB  - Progesterone stimulation of Xenopus oocyte maturation requires the cytoplasmic
      polyadenylation-induced translation of mos and cyclin B mRNAs. One cis element
      that drives polyadenylation is the CPE, which is bound by the protein CPEB.
      Polyadenylation is stimulated by Aurora A (Eg2)-catalyzed CPEB serine 174
      phosphorylation, which occurs soon after oocytes are exposed to progesterone.
      Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174
      phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation.
      However, these insulin-induced events are uniquely controlled by PI3 kinase and
      PKC-zeta, which act upstream of Aurora A. The intersection of the progesterone
      and insulin signaling pathways occurs at glycogen synthase kinase 3 (GSK-3),
      which regulates the activity of Aurora A. GSK-3 and Aurora A interact in vivo,
      and overexpressed GSK-3 inhibits Aurora A-catalyzed CPEB phosphorylation. In
      vitro, GSK-3 phosphorylates Aurora A on S290/291, the result of which is an
      autophosphorylation of serine 349. GSK-3 phosphorylated Aurora A, or Aurora A
      proteins with S290/291D or S349D mutations, have reduced or no capacity to
      phosphorylate CPEB. Conversely, Aurora A proteins with S290/291A or S349A
      mutations are constitutively active. These results suggest that the progesterone
      and insulin stimulate maturation by inhibiting GSK-3, which allows Aurora A
      activation and CPEB-mediated translation.

PMID- 14724179
TI  - Loss of the anaphase-promoting complex in quiescent cells causes unscheduled
      hepatocyte proliferation.
AB  - The anaphase-promoting complex or cyclosome (APC/C) is an ubiquitin protein
      ligase that together with Cdc20 and Cdh1 targets mitotic proteins for degradation
      by the proteosome. APC-Cdc20 activity during mitosis triggers anaphase by
      destroying securin and cyclins. APC-Cdh1 promotes degradation of cyclins and
      other proteins during G(1). We show that loss of APC/C during embryogenesis is
      early lethal before embryonic day E6.5 (E6.5). To investigate the role of APC/C
      in quiescent cells, we conditionally inactivated the subunit Apc2 in mice.
      Deletion of Apc2 in quiescent hepatocytes caused re-entry into the cell cycle and
      arrest in metaphase, resulting in liver failure. Re-entry into the cell cycle
      either occurred without any proliferative stimulus or could be easily induced. We
      demonstrate that the APC has an additional function to prevent hepatocytes from
      unscheduled re-entry into the cell cycle.

PMID- 14724180
TI  - Single cGMP-activated Ca(+)-dependent Cl(-) channels in rat mesenteric artery
      smooth muscle cells.
AB  - The present study describes the single channel properties of a novel cGMP
      activated Ca(2+)-dependent Cl(-) channel in rat mesenteric artery smooth muscle
      cells. Single channel currents were recorded in cell-attached patches in the
      presence of 8 Br cGMP in response to the addition of caffeine or noradrenaline
      and in both outside-out and inside-out patches when the internal patch surface
      was bathed in cGMP and Ca(2+). The channels were permeable to Cl(-) ions with an
      anion permeability sequence of SCN(-) (1.7) > Cl(-) (1.0) > I(-) (0.6). Single
      channel mean open probability (NP(o)) was independent of voltage and the channels
      displayed three conductance levels of 15, 35 and 55 pS. cGMP was required for
      channel activation and the single channel NP(o) increased sharply with raised
      [Ca(2+)](i), maximal activation occurring at a [Ca(2+)](i) of about 100 nM. The
      relationship between NP(o) and cGMP concentration was voltage independent and
      could be fitted by the Hill equation giving a K(d) of about 3 microM and a Hill
      coefficient (n(H)) of 3. cGMP- and Ca(2+)-dependent channel currents were
      inhibited by 10 microM ZnCl(2) but niflumic acid, an inhibitor of Ca(2+)
      activated Cl(-) channels, had no effect. Inhibition of cGMP-dependent protein
      kinase activity by the cGMP-dependent protein kinase inhibitor KT5823 or
      replacement of ATP by AMP-PNP reduced NP(o), while activation of cGMP-dependent
      protein kinase by guanosine 3', 5'-cyclic monophosphate, beta-phenyl-1, N(2)
      etheno-8-bromo-sodium salt (8 Br PET cGMP) produced a significant increase in
      single channel NP(o). It is likely that these single channel currents underlie
      the noradrenaline-activated inward current important for vasomotion in these
      resistance arteries.

PMID- 14724181
TI  - Basolateral Na+-H+ exchanger-1 in rat taste receptor cells is involved in neural
      adaptation to acidic stimuli.
AB  - The role of basolateral Na(+)-H(+) exchanger isoform-1 (NHE-1) was investigated
      in neural adaptation of rat taste responses to acidic stimuli, by direct
      measurement of intracellular pH (pH(i)) in polarized taste receptor cells (TRCs)
      and by chorda tympani (CT) taste nerve recordings. In TRCs perfused with
      CO(2)/HCO(3)(-)-free solution (pH 7.4), removal of basolateral Na(+) decreased
      pH(i) reversibly and zoniporide, a specific NHE-1 blocker, inhibited the Na(+)
      induced changes in pH(i). The spontaneous rate of TRC pH(i) recovery from NH(4)Cl
      pulses was inhibited by basolateral zoniporide with a K(i) of 0.33microm.
      Exposure to basolateral ionomycin, reversibly increased TRC Ca(2+), resting
      pH(i), and the spontaneous rate of pH(i) recovery from an NH(4)Cl pulse. These
      effects of Ca(2+) on pH(i) were blocked by zoniporide. In in vivo experiments,
      topical lingual application of zoniporide increased the magnitude of the CT
      responses to acetic acid and CO(2), but not to HCl. Topical lingual application
      of ionomycin did not affect the phasic part of the CT responses to acidic
      stimuli, but decreased the tonic part by 50% of control over a period of about 1
      min. This increased adaptation in the CT response was inhibited by zoniporide.
      Topical lingual application of 8-CPT-cAMP increased the CT responses to HCl, but
      not to CO(2), and acetic acid. In the presence of cAMP, ionomycin increased
      sensory adaptation to HCl, CO(2), and acetic acid. Thus, cAMP and Ca(2+)
      independently modulate CT responses to acidic stimuli. While cAMP enhances TRC
      apical H(+) entry and CT responses to strong acid, an increase in Ca(2+)
      activates NHE-1, and increases neural adaptation to all acidic stimuli.

PMID- 14724182
TI  - Phasic negative intrathoracic pressures enhance the vascular responses to
      stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized
      dogs.
AB  - We investigated whether the reflex responses to stimulation of pulmonary arterial
      baroreceptors were altered by intrathoracic pressure changes similar to those
      encountered during normal breathing. Dogs were anaesthetized with alpha
      chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and
      its main branches as far as the first lobar arteries were vascularly isolated and
      perfused with venous blood. The chest was closed following connection to the
      perfusion circuit and pressures distending the aortic arch, carotid sinus and
      coronary artery baroreceptors were controlled. Changes in the descending aortic
      (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in
      systemic vascular resistance. Values of SPP were plotted against mean pulmonary
      arterial pressure (PAP) and sigmoid functions applied. From these curves we
      derived the threshold pressures (corresponding to 5% of the overall response of
      SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP
      (equivalent to 'set point'). Stimulus-response curves were compared between data
      obtained with intrathoracic pressure at atmospheric and with a phasic
      intrathoracic pressure ranging from atmospheric to around -10 mmHg (18 cycles
      min(-1)). Results were obtained from seven dogs and are given as means +/-S.E.M.
      Compared to the values obtained when intrathoracic pressure was at atmospheric,
      the phasic intrathoracic pressure decreased the pulmonary arterial threshold
      pressure in five dogs; average change from 28.4 +/- 5.9 to 19.3 +/- 5.9 mmHg (P >
      0.05). The inflexion pressure was significantly reduced from 37.8 +/- 4.8 to 27.4
      +/- 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently
      changed. These results have shown that a phasic intrathoracic pressure, which
      simulates respiratory oscillations, displaces the stimulus-response curve of the
      pulmonary arterial baroreceptors to lower pressures so that it lies within a
      physiological range of pressures.

PMID- 14724183
TI  - A pharmacological profile of the aldehyde receptor repertoire in rat olfactory
      epithelium.
AB  - Several lines of evidence suggest that odorants are recognized through a
      combinatorial process in the olfactory system; a single odorant is recognized by
      multiple receptors and multiple odorants are recognized by the same receptor.
      However few details of how this might actually function for any particular odour
      set or receptor family are available. Approaching the problem from the ligands
      rather than the receptors, we used the response to a common odorant, octanal, as
      the basis for defining multiple receptor profiles. Octanal and other aldehydes
      induce large EOG responses in the rodent olfactory epithelium, suggesting that
      these compounds activate a large number of odour receptors (ORs). Here, we have
      determined and compared the pharmacological profile of different octanal
      receptors using Ca(2+) imaging in isolated olfactory sensory neurones (OSNs). It
      is believed that each OSN expresses only one receptor, thus the response profile
      of each cell corresponds to the pharmacological profile of one particular
      receptor. We stimulated the cells with a panel of nine odorants, which included
      octanal, octanoic acid, octanol and cinnamaldehyde among others (all at
      30microM). Cluster analysis revealed several distinct pharmacological profiles
      for cells that were all sensitive to octanal. Some receptors had a broad
      molecular range, while others were activated only by octanal. Comparison of the
      profiles with that of the one identified octanal receptor, OR-I7, indicated
      several differences. While OR-I7 is activated by low concentrations of octanal
      and blocked by citral, other receptors were less sensitive to octanal and not
      blocked by citral. A lower estimate for the maximal number of octanal receptors
      is between 33 and 55. This large number of receptors for octanal suggests that,
      although the peripheral olfactory system is endowed with high sensitivity,
      discrimination among different compounds probably requires further central
      processing.

PMID- 14724184
TI  - The effect of mitochondrial inhibitors on membrane currents in isolated neonatal
      rat carotid body type I cells.
AB  - Inhibitors of mitochondrial energy metabolism have long been known to be potent
      stimulants of the carotid body, yet their mechanism of action remains obscure. We
      have therefore investigated the effects of rotenone, myxothiazol, antimycin A,
      cyanide (CN(-)) and oligomycin on isolated carotid body type I cells. All five
      compounds caused a rapid rise in intracellular Ca(2+), which was inhibited on
      removal of extracellular Ca(2+). Under current clamp conditions rotenone and CN(
      ) caused a rapid membrane depolarization and elevation of [Ca(2+)](i). Voltage
      clamping cells to -70 mV substantially attenuated this rise in [Ca(2+)](i).
      Rotenone, cyanide, myxothiazol and oligomycin significantly inhibited resting
      background K(+) currents. Thus rotenone, myxothiazol, cyanide and oligomycin
      mimic the effects of hypoxia in that they all inhibit background K(+) current
      leading to membrane depolarization and voltage-gated calcium entry. Hypoxia,
      however, failed to have any additional effect upon membrane currents in the
      presence of CN(-) or rotenone or the mitochondrial uncoupler p
      trifluoromethoxyphenyl hydrazone (FCCP). Thus not only do mitochondrial
      inhibitors mimic the effects of hypoxia, but they also abolish oxygen
      sensitivity. These observations suggest that there is a close link between oxygen
      sensing and mitochondrial function in type I cells. Mechanisms that could account
      for this link and the actions of mitochondrial inhibitors are discussed.

PMID- 14724185
TI  - Influence of endogenous nitric oxide on sympathetic vasoconstriction in normoxia,
      acute and chronic systemic hypoxia in the rat.
AB  - We studied the role of nitric oxide (NO) in blunting sympathetically evoked
      muscle vasoconstriction during acute and chronic systemic hypoxia. Experiments
      were performed on anaesthetized normoxic (N) and chronically hypoxic (CH) rats
      that had been acclimated to 12% O(2) for 3-4 weeks. The lumbar sympathetic chain
      was stimulated for 1 min with bursts at 20 or 40 Hz and continuously at 2 Hz. In
      N rats, acute hypoxia (breathing 8% O(2)) reduced baseline femoral vascular
      resistance (FVR) and depressed increases in FVR evoked by all three patterns of
      stimulation, but infusion of the NO donor sodium nitroprusside (SNP), so as to
      similarly reduce baseline FVR, did not affect sympathetically evoked responses.
      Blockade of NO synthase (NOS) with L-NAME increased baseline FVR and facilitated
      the sympathetically evoked increases in FVR, but when baseline FVR was restored
      by SNP infusion, these evoked responses were restored. Acute hypoxia after L-NAME
      still reduced baseline FVR and depressed evoked responses. In CH rats breathing
      12% O(2), baseline FVR was lower than in N rats breathing air, but L-NAME had
      qualitatively similar effects on baseline FVR and sympathetically evoked
      increases in FVR. SNP similarly restored baseline FVR and evoked responses.
      Inhibition of neuronal NOS or inducible NOS did not affect baselines, or evoked
      responses. We propose that in N and CH rats sympathetically evoked muscle
      vasoconstriction is modulated by tonically released NO, but not depressed by
      additional NO released on sympathetic activation. The present results suggest
      that hypoxia-induced blunting of sympathetic vasoconstriction in skeletal muscle
      is not mediated by NO.

PMID- 14724186
TI  - Regulation of Kv4.3 voltage-dependent gating kinetics by KChIP2 isoforms.
AB  - We conducted a kinetic analysis of the voltage dependence of macroscopic
      inactivation (tau(fast), tau(slow)), closed-state inactivation
      (tau(closed,inact)), recovery (tau(rec)), activation (tau(act)), and deactivation
      (tau(deact)) of Kv4.3 channels expressed alone in Xenopus oocytes and in the
      presence of the calcium-binding ancillary subunits KChIP2b and KChIP2d. We
      demonstrate that for all expression conditions, tau(rec), tau(closed,inact) and
      tau(fast) are components of closed-state inactivation transitions. The values of
      tau(closed,inact) and tau(fast) monotonically merge from -30 to -20 mV while the
      values of tau(closed,inact) and tau(rec) approach each other from -60 to -50 mV.
      These data generate classic bell-shaped time-constant-potential curves. With the
      KChIPs, these curves are distinct from that of Kv4.3 expressed alone due to
      acceleration of tau(rec) and slowing of tau(closed,inact) and tau(fast). Only at
      depolarized potentials where channels open is tau(slow) detectable suggesting
      that it represents an open-state inactivation mechanism. With increasing
      depolarization, KChIPs favour this open-state inactivation mechanism, supported
      by the observation of larger transient reopening currents upon membrane
      hyperpolarization compared to Kv4.3 expressed alone. We propose a Kv4.3 gating
      model wherein KChIP2 isoforms accelerate recovery, slow closed-state
      inactivation, and promote open-state inactivation. This model supports the
      observations that with KChIPs, closed-state inactivation transitions are
      [Ca(2+)](i)-independent, while open-state inactivation is [Ca(2+)](i)-dependent.
      The selective KChIP- and Ca(2+)-dependent modulation of Kv4.3 inactivation
      mechanisms predicted by this model provides a basis for dynamic modulation of the
      native cardiac transient outward current by intracellular Ca(2+) fluxes during
      the action potential.

PMID- 14724187
TI  - Effects of strength training on muscle lactate release and MCT1 and MCT4 content
      in healthy and type 2 diabetic humans.
AB  - Lactate is released from skeletal muscle in proportion to glucose uptake rates,
      and it leaves the cells via simple diffusion and two monocarboxylate transporter
      proteins, MCT1 and MCT4. In response to endurance training MCT1 - and possibly
      MCT4 - content in muscle increases. The MCTs have not previously been measured in
      patients with type 2 diabetes (Type 2), and the response to strength training is
      unknown. Ten Type 2 and seven healthy men (Control) strength-trained one leg (T)
      3 times a week for 6 weeks while the other leg remained untrained (UT). Each
      session lasted no more than 30 min. After strength training, muscle biopsies were
      obtained and an isoglycaemic, hyperinsulinaemic clamp, combined with arterial and
      femoral venous catheterization of both legs, was carried out. During
      hyperinsulinaemia lactate release was always increased in T versus UT legs. MCT1
      was lower (P<0.05) and MCT4 similar in Type 2 versus Control. With training, MCT1
      content always increased, while MCT4 only increased in Control. CONCLUSIONS: MCT1
      content in skeletal muscle in Type 2 is lower compared with healthy men. Strength
      training increases MCT1 content in healthy men and in Type 2, thus normalizing
      the content in Type 2.

PMID- 14724188
TI  - Voltage-activated Ca(2+) channels and their role in the endocrine function of the
      pituitary gland in newborn and adult mice.
AB  - We have prepared fresh pituitary gland slices from adult and, for the first time,
      from newborn mice to assess modulation of secretory activity via voltage
      activated Ca(2+) channels (VACCs). Currents through VACCs and membrane
      capacitance have been measured with the whole-cell patch-clamp technique.
      Melanotrophs in newborns were significantly larger than in adults. In both
      newborn and adult melanotrophs activation of VACCs triggered exocytosis. All
      pharmacologically isolated VACC types contributed equally to the secretory
      activity. However, the relative proportion of VACCs differed between newborns and
      adults. In newborn cells L-type channels dominated and, in addition, an exclusive
      expression of a toxin-resistant R-type-like current was found. The expression of
      L-type VACCs was up-regulated by the increased oestrogen levels observed in
      females, and was even more emphasized in the cells of pregnant females and
      oestrogen-treated adult male mice. We suggest a general mechanism modulating
      endocrine secretion in the presence of oestrogen and particularly higher
      sensitivity to treatments with L-type channel blockers during high oestrogen
      physiological states.

PMID- 14724189
TI  - Roles of compatible osmolytes and heat shock protein 70 in the induction of
      tolerance to stresses in porcine endothelial cells.
AB  - Studies of the responses of porcine pulmonary endothelial cells to acute
      hypertonic stress have been extended by examining the induction and underlying
      mechanisms of cell tolerance to both osmotic and heat stresses. Preliminary
      adaptation of these cells to 0.4osmol (kg H(2)O)(-1) rendered them tolerant
      either to subsequent severe osmotic stress (0.7osmol (kg H(2)O)(-1)) or to
      subsequent severe heat shock (50 min at 49 degrees C). In contrast, preliminary
      exposure of the cells to mild heat shock (44 degrees C for 30 min) induced
      tolerance only to severe heat shock, not to hyperosmotic stress. Induction of
      tolerance to heat shock by either procedure correlated with the induced
      expression of heat shock protein 70 (HSP70). Induction of tolerance to
      hyperosmotic stress, on the other hand, was associated with the cellular
      accumulation of osmolytes, such as amino acids, betaine and myo-inositol, and did
      not correlate with the induced expression of HSP70. It also required a reduction
      in the final change of osmotic pressure applied to the cells, such that maximum
      cell shrinkage would not be much more than 40%. In general, therefore, HSP70 and
      compatible osmolytes have distinct roles in cellular adaptation to these
      stresses.

PMID- 14724190
TI  - Functional and structural conservation of CBS domains from CLC chloride channels.
AB  - All eukaryotic CLC Cl(-) channel subunits possess a long cytoplasmic carboxy
      terminus that contains two so-called CBS (cystathionine beta-synthase) domains.
      These domains are found in various unrelated proteins from all phylae. The
      crystal structure of the CBS domains of inosine monophosphate dehydrogenase
      (IMPDH) is known, but it is not known whether this structure is conserved in CLC
      channels. Working primarily with ClC-1, we used deletion scanning mutagenesis,
      coimmunoprecipitation and electrophysiology to demonstrate that its CBS domains
      interact. The replacement of CBS domains of ClC-1 with the corresponding CBS
      domains from other CLC channels and even human IMPDH yielded functional channels,
      indicating a high degree of structural conservation. Based on a homology model of
      the pair of CBS domains of CLC channels, we identified some residues that, when
      mutated, affected the common gate which acts on both pores of the dimeric
      channel. Thus, we propose that the structure of CBS domains from CLC channels is
      highly conserved and that they play a functional role in the common gate.

PMID- 14724191
TI  - Rat transcobalamin: cloning and regulation of mRNA expression.
AB  - Transcobalamin (TC) has been cloned and used for studying its gene expression in
      the rat. TC mRNA is distributed widely in adult rat tissues, but at different
      levels (kidney > liver > lung > yolk sac > intestine > heart > brain > spleen >
      muscle). TC mRNA levels were 4-fold higher in the jejunum and ileum compared to
      its levels in the duodenum. During postnatal development, TC mRNA levels in the
      ileum declined 4-fold from day 4 to day 12, but increased by 5-fold between days
      12 and 24. In contrast, TC mRNA levels increased by 2.5-fold in the kidney from
      day 4 to day 12 and then declined by 2-fold by day 24. Adrenalectomy of adult
      rats resulted in a 4-fold decline in ileal levels of TC mRNA and a 50% decline in
      the ileal mucosal formation of the TC-[(57)Co] cobalamin (Cbl) complex following
      oral administration of [(57)Co]Cbl complexed to gastric intrinsic factor (IF).
      Cortisone treatment reversed these changes noted in the ileum. In contrast to
      ileum, kidney TC mRNA levels were not altered significantly in adrenalectomized
      rats before and after cortisone treatment. Taken together, this study has
      provided evidence for the regulation of TC gene expression in the rat kidney and
      intestine during their postnatal development, and cortisone selectively regulates
      ileal but not kidney TC mRNA levels.

PMID- 14724192
TI  - Calcium-induced calcium release regulates action potential generation in guinea
      pig sympathetic neurones.
AB  - Experiments were done using guinea-pig sympathetic neurones dissociated from the
      stellate ganglia to establish whether calcium-induced calcium release (CICR)
      modulated action potential (AP) generation in mammalian neurones. Using
      measurements of intracellular calcium ([Ca(2+)](i)) with the Ca(2+)-sensitive dye
      fluo-3, we demonstrated that 10 mM caffeine activated ryanodine receptors and
      caused a rise in [Ca(2+)](i) in both Ca(2+)-containing and Ca(2+)-deficient
      solutions. We also demonstrated that combined treatment with caffeine and 1
      microm thapsigargin or caffeine and 20 microm ryanodine blocked subsequent
      caffeine-induced elevations of [Ca(2+)](i). Treatment with thapsigargin,
      ryanodine or 200 microM Cd(2+) to disrupt CICR decreased the latency to AP
      generation during 400 ms depolarizing current ramps using the perforated patch
      whole cell patch clamp in current clamp mode. Treatment with 500 microM
      tetraethylammonium also decreased the latency to AP generation during
      depolarizing current ramps in control cells, but not in cells pretreated with
      thapsigargin to deplete internal Ca(2+) stores. In summary, we propose that an
      outward current, carried at least in part through BK channels, is activated by
      CICR at membrane voltages approaching the threshold for AP initiation and that
      this current opposed depolarizing current ramps applied to guinea-pig sympathetic
      stellate neurones.

PMID- 14724194
TI  - Extracellular signal-regulated kinase activation and endothelin-1 production in
      human endothelial cells exposed to vibration.
AB  - Hand-arm vibration syndrome is a vascular disease of occupational origin and a
      form of secondary Raynaud's phenomenon. Chronic exposure to hand-held vibrating
      tools may cause endothelial injury. This study investigates the biomechanical
      forces involved in the transduction of fluid vibration in the endothelium. Human
      endothelial cells were exposed to direct vibration and rapid low-volume fluid
      oscillation. Rapid low-volume fluid oscillation was used to simulate the effects
      of vibration by generating defined temporal gradients in fluid shear stress
      across an endothelial monolayer. Extracellular signal-regulated kinase (ERK1/2)
      phosphorylation and endothelin-1 (ET-1) release were monitored as specific
      biochemical markers for temporal gradients and endothelial response,
      respectively. Both vibrational methods were found to phosphorylate ERK1/2 in a
      similar pattern. At a fixed frequency of fluid oscillation where the duration of
      each pulse cycle remained constant, ERK1/2 phosphorylation increased with the
      increasing magnitude of the applied temporal gradient. However, when the
      frequency of flow oscillation was increased (thus decreasing the duration of each
      pulse cycle), ERK1/2 phosphorylation was attenuated across all temporal gradient
      flow profiles. Fluid oscillation significantly stimulated ET-1 release compared
      to steady flow, and endothelin-1 was also attenuated with the increase in
      oscillation frequency. Taken together, these results show that both the absolute
      magnitude of the temporal gradient and the frequency/duration of each pulse cycle
      play a role in the biomechanical transduction of fluid vibrational forces in
      endothelial cells. Furthermore, this study reports for the first time a link
      between the ERK1/2 signal transduction pathway and transmission of vibrational
      forces in the endothelium.

PMID- 14724193
TI  - Medullary serotonergic neurones and adjacent neurones that express neurokinin-1
      receptors are both involved in chemoreception in vivo.
AB  - Neurokinin-1 receptor (NK1R)-expressing neurones that are involved in
      chemoreception at the retrotrapezoid nucleus (Nattie & Li, 2002b) are also
      prominent at locations that contain medullary serotonergic neurones, which are
      chemosensitive in vitro. In medullary regions containing both types, we evaluated
      their role in central chemoreception by specific cell killing. We injected (2 x
      100 nl) (a) substance P-saporin (SP-SAP; 1 microm) to kill NK1R-expressing
      neurones, (b) a novel conjugate of a monoclonal antibody to the serotonin
      transporter (SERT) and saporin (anti-SERT-SAP; 1 microm) to kill serotonergic
      neurones, or (c) SP-SAP and anti-SERT-SAP together to kill both types. Controls
      received IgG-SAP injections (1 microm). There was no double-labelling of NK1R
      immunoreactive (ir) and tryptophan-hydroxylase (TPOH)-ir neurones. Cell (somatic
      profile) counts showed that NK1R-ir neurones in the SP-SAP group were reduced by
      31%; TPOH-ir neurones in the anti-SERT-SAP group by 28%; and NK1R-ir and TPOH-ir
      neurones, respectively, in the combined lesion group by 55% and 31% (P < 0.001;
      two-way ANOVA; P < 0.05, Tukey's post hoc test). The treatments had no
      significant effect on sleep/wake time, body temperature, or oxygen consumption
      but all three reduced the ventilatory response to 7% inspired CO(2) in
      wakefulness and sleep by a similar amount. SP-SAP treatment decreased the
      averaged CO(2) responses (3, 7 and 14 days after lesions) in wakefulness and
      sleep by 21% and 16%, anti-SERT-SAP decreased the responses by 15% and 18%, and
      the combined treatment decreased the responses by 12% and 12% (P < 0.001; two-way
      ANOVA; P < 0.05, Tukey's post hoc test). We conclude that separate populations of
      serotonergic and adjacent NK1R-expressing neurones in the medulla are both
      involved in central chemoreception in vivo.

PMID- 14724195
TI  - The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.
AB  - Functional and structural studies demonstrate that Cl(-) channels of the ClC
      family have a dimeric double-barrelled structure, with each monomer contributing
      an identical pore. Single protopore gating is a fast process dependent on Cl(-)
      interaction within the selectivity filter and in ClC-0 has a low temperature
      coefficient over a 10 degrees C range (Q(10)). A slow gating process closes both
      protopores simultaneously, has a high Q(10), is facilitated by extracellular
      Zn(2+) and Cd(2+) and is abolished or markedly reduced by mutation of a cysteine
      conserved in ClC-0, -1 and -2. In order to test the hypothesis that similar slow
      and fast gates exist in the widely expressed ClC-2 Cl(-) channel we have
      investigated the effects of these manoeuvres on ClC-2. We find that the time
      constants of both components of the double-exponential hyperpolarization
      dependent activation (and deactivation) processes have a high temperature
      dependence, with Q(10) values of about 4-5, suggesting important conformational
      changes of the channel. Mutating C256 (equivalent to C212 in ClC-0) to A, led to
      a significant fraction of constitutively open channels at all potentials.
      Activation time constants were not affected but deactivation was slower and
      significantly less temperature dependent in the C256A mutant. Extracellular
      Cd(2+), that inhibits wild-type (WT) channels almost fully, inhibited C256A only
      by 50%. In the WT, the time constants for opening were not affected by Cd(2+) but
      deactivation at positive potentials was accelerated by Cd(2+). This effect was
      absent in the C256A mutant. The effect of intracellular Cl(-) on channel
      activation was unchanged in the C256A mutant. Collectively our results strongly
      support the hypothesis that ClC-2 possesses a common gate and that part of the
      current increase induced by hyperpolarization represents an opening of the common
      gate. In contrast to the gating in ClC-0, the protopore gate and the common gate
      of ClC-2 do not appear to be independent.

PMID- 14724196
TI  - Transient receptor potential-like channels mediate metabotropic glutamate
      receptor EPSCs in rat dopamine neurones.
AB  - Transient receptor potential (TRP) channels form cationic channels activated by
      diverse factors including mechanical stimuli, changes in osmolarity, pH and
      temperature, as well as the exogenous irritant, capsaicin. Metabotropic glutamate
      receptors have also recently been linked to TRP channel activation in neurones of
      the substantia nigra, hippocampus and cerebellum, suggesting a novel role for
      such channels in synaptic communication via endogenous neurotransmitters. We
      tested this for dopamine neurones in rat brain slices by characterizing the
      current-voltage relationship and pharmacology of EPSCs mediated by group I
      metabotropic glutamate receptor subtype 1 (mGluR1). Slow inward currents (273 +/-
      35 pA peak amplitude, 381 +/- 25 ms latency, holding potential (V(h)) =-73 mV)
      representing evoked mGluR1 EPSCs were isolated in the presence of antagonists of
      AMPA, NMDA, GABA(A), GABA(B), muscarinic and glycine receptors. CPCCOEt (100
      microM), an mGluR1 antagonist, blocked the residual EPSC in all recordings.
      mGluR1-activated EPSCs reversed polarity near -10 mV, consistent with the
      involvement of a cationic channel. Extracellular application of the non-selective
      TRP channel blockers SKF 96365, flufenamic acid and ruthenium red caused
      reversible inhibition of mGluR1-activated EPSCs. These characteristics parallel
      those of mGluR1 activation with an agonist and indicate the involvement of a TRP
      like channel in mGluR1-mediated EPSCs.

PMID- 14724197
TI  - Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in
      neonatal rat in vitro.
AB  - The specific role of the neuromodulator substance P (SP) and its target, the
      neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory
      activity is not known. The preBotzinger complex (preBotC), an essential site for
      respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones
      that are strongly modulated by exogenously applied SP or acute pharmacological
      blockade of NK1Rs. We investigated the effects of capsaicin, which depletes
      neuropeptides (including SP) and glutamate from presynaptic terminals, on
      respiratory motor output in medullary slice preparations of neonatal rat that
      generate respiratory-related activity. Bath application of capsaicin slowed
      respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm
      could be restored by bath application of SP or glutamate transporter blockers.
      Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres
      within the preBotC. Our results suggest that depletion of SP (or other peptides)
      and/or glutamate by capsaicin causes a cessation of respiratory rhythm in
      neonatal rat slices.

PMID- 14724198
TI  - Modulation of excitatory synaptic transmission in the spinal substantia
      gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit.
AB  - Functional kainate (KA) receptors (KARs) are expressed in the spinal cord
      substantia gelatinosa (SG) region, and their activation has a capacity to
      modulate excitatory synaptic transmission at primary afferent synapses with SG
      neurones. In the present study, we have used gene-targeted mice lacking KAR GluR5
      and/or GluR6 subunits to determine the identity of the receptor subunits involved
      in the KA-induced modulation of excitatory transmission. Our findings reveal that
      KARs comprising GluR5 or GluR6 subunits can either suppress or facilitate
      glutamatergic excitatory transmission in the SG of acutely prepared adult mouse
      spinal cord slices. In the absence of synaptic inhibition mediated by GABA(A) and
      glycine receptors, a biphasic effect of kainate is characteristic with
      facilitation apparent at a low concentration (30 nM) and depression at a higher
      concentration (3 microM). In addition, GluR6-KARs, localizing pre- and
      postsynaptically, are critically involved in inhibiting transmission at both A
      delta and C fibre monosynaptic pathways, whereas presynaptic GluR5-KARs play a
      limited role in inhibiting the C fibre-activated pathway. The results obtained
      support the hypothesis that KARs are involved in bi-directional regulation of
      excitatory synaptic transmission in the spinal cord SG region, and that these
      actions may be of critical importance for nociception and the clinical treatment
      of pain.

PMID- 14724199
TI  - Post-spike distance-to-threshold trajectories of neurones in monkey motor cortex.
AB  - A recently developed method permits calculation of the post-spike distance-to
      threshold trajectory from an extracellularly recorded spontaneous spike train,
      using a transform of the interspike interval histogram. We applied this method to
      61 single neurones recorded from the primary motor cortex of an awake behaving
      monkey; 39 cells were antidromically identified as pyramidal tract neurones
      (PTNs). The cells fell into three categories. Fifty-three trajectories (37 from
      PTNs) had statistically significant peaks 10-60 ms after the preceding spike. Six
      neurones (2 PTNs) had non-peaked trajectories which rose exponentially towards
      threshold. Two cells (both unidentified) had trajectories which declined
      monotonically away from threshold with increasing post-spike latency. The peaked
      trajectories were unlikely simply to be an artefact of changing firing rate,
      which potentially can invalidate this method. Firstly, computer simulations
      confirmed that the method could accurately re-create both exponential and peaked
      trajectories, even in the presence of the same rate modulation as seen
      experimentally. Secondly, the responses of eight cells to weak single pulse
      intracortical microstimulation (20 microA) through a nearby electrode were
      measured. For each cell, including representatives of all three trajectory
      shapes, the modulation of response probability with post-spike latency was
      consistent with the trajectory computed from the spontaneous discharge. We also
      demonstrated that cells showed a peaked trajectory during periods with either
      high or low spontaneous network oscillations, so that the peaks were likely to be
      generated in part by single cell properties rather than exclusively by network
      activity. We conclude that many single neurones in motor cortex have an increased
      probability of firing a spike around 30 ms after the previous action potential.
      This could act to enhance synchronized oscillatory discharge among populations of
      cells at functionally relevant frequencies.

PMID- 14724200
TI  - Intrinsic cellular currents and the temporal precision of EPSP-action potential
      coupling in CA1 pyramidal cells.
AB  - We examined relations between cellular currents activated near firing threshold
      and the initiation of action potentials by excitatory postsynaptic potentials
      (EPSPs) in CA1 pyramidal cells in vitro. Small voltage steps elicited sequences
      of inward-outward currents at hyperpolarized potentials, but evoked largely
      inward currents at near threshold potentials. Similarly small EPSP-like waveforms
      initiated largely inward currents while larger stimuli evoked sequences of inward
      followed by outward currents. Shorter rise times of EPSP-like waveforms
      accentuated a transient component of inward currents. Voltage clamp data were
      consistent with the voltage dependence of current clamp responses to injection of
      EPSP shaped waveforms. Small events were prolonged at subthreshold potentials and
      could elicit action potentials at long latencies while responses to larger EPSP
      waveforms showed less voltage dependence and tended to induce spikes at shorter,
      less variable latencies. The precision of action potentials initiated by white
      noise depended also on stimulus amplitude. High variance stimuli induced firing
      with high precision, while the timing of spikes induced by lower variance signals
      was more variable between trials. In voltage clamp records, high variance noise
      commands induced sequences of inward followed by outward currents, while lower
      variance versions of the same commands elicited purely inward currents. These
      data suggest that larger synaptic stimuli recruit outward as well as inward
      currents. The resulting inward-outward current sequences enhance the temporal
      precision of EPSP-spike coupling. Thus, CA1 pyramidal cells initiate action
      potentials with different temporal precision, depending on stimulus properties.

PMID- 14724201
TI  - Dynamic properties of corticogeniculate excitatory transmission in the rat dorsal
      lateral geniculate nucleus in vitro.
AB  - The feedback excitation from the primary visual cortex to principal cells in the
      dorsal lateral geniculate nucleus (dLGN) is markedly enhanced with firing
      frequency. This property presumably reflects the ample short-term plasticity at
      the corticogeniculate synapse. The present study aims to explore
      corticogeniculate excitatory postsynaptic currents (EPSCs) evoked by brief trains
      of stimulation with whole-cell patch-clamp recordings in dLGN slices from DA-HAN
      rats. The EPSCs rapidly increased in amplitude with the first two or three
      impulses followed by a more gradual growth. A double exponential function with
      time constants 39 and 450 ms empirically described the growth for 5-25Hz trains.
      For lower train frequencies (down to 1Hz) a third component with time constant
      4.8 s had to be included. The different time constants are suggested to represent
      fast and slow components of facilitation and augmentation. The time constant of
      the fast component changed with the extracellular calcium ion concentration as
      expected for a facilitation mechanism involving an endogenous calcium buffer that
      is more efficiently saturated with larger calcium influx. Concerning the function
      of the corticogeniculate feedback pathway, the different components of short-term
      plasticity interacted to increase EPSC amplitudes on a linear scale to firing
      frequency in the physiological range. This property makes the corticogeniculate
      synapse well suited to function as a neuronal amplifier that enhances the
      thalamic transfer of visual information to the cortex.

PMID- 14724202
TI  - Sub- and suprathreshold receptive field properties of pyramidal neurones in
      layers 5A and 5B of rat somatosensory barrel cortex.
AB  - Layer 5 (L5) pyramidal neurones constitute a major sub- and intracortical output
      of the somatosensory cortex. This layer 5 is segregated into layers 5A and 5B
      which receive and distribute relatively independent afferent and efferent
      pathways. We performed in vivo whole-cell recordings from L5 neurones of the
      somatosensory (barrel) cortex of urethane-anaesthetized rats (aged 27-31 days).
      By delivering 6 deg single whisker deflections, whisker pad receptive fields were
      mapped for 16 L5A and 11 L5B neurones located below the layer 4 whisker-barrels.
      Average resting membrane potentials were -75.6 +/- 1.1 mV, and spontaneous action
      potential (AP) rates were 0.54 +/- 0.14 APs s(-1). Principal whisker (PW) evoked
      responses were similar in L5A and L5B neurones, with an average 5.0 +/- 0.6 mV
      postsynaptic potential (PSP) and 0.12 +/- 0.03 APs per stimulus. The layer 5A sub
      and suprathreshold receptive fields (RFs) were more confined to the principle
      whisker than those of layer 5B. The basal dendritic arbors of layer 5A and 5B
      cells were located below both layer 4 barrels and septa, and the cell bodies were
      biased towards the barrel walls. Responses in both L5A and L5B developed slowly,
      with onset latencies of 10.1 +/- 0.5 ms and peak latencies of 33.9 +/- 3.3 ms.
      Contralateral multi-whisker stimulation evoked PSPs similar in amplitude to those
      of PW deflections; whereas, ipsilateral stimulation evoked smaller and longer
      latency PSPs. We conclude that in L5 a whisker deflection is represented in two
      ways: focally by L5A pyramids and more diffusely by L5B pyramids as a result of
      combining different inputs from lemniscal and paralemniscal pathways. The
      relevant output evoked by a whisker deflection could be the ensemble activity in
      the anatomically defined cortical modules associated with a single or a few
      barrel-columns.

PMID- 14724203
TI  - Augmentation of corticogeniculate EPSCs in principal cells of the dorsal lateral
      geniculate nucleus of the rat investigated in vitro.
AB  - Augmentation is a component of short-term synaptic plasticity with a gradual
      onset and duration in seconds. To investigate this component at the
      corticogeniculate synapse, whole cell patch-clamp recordings were obtained from
      principal cells in a slice preparation of the rat dorsal lateral geniculate
      nucleus. Trains with 10 stimuli at 25 Hz evoked excitatory postsynaptic currents
      (EPSCs) that grew in amplitude, primarily from facilitation. Such trains also
      induced augmentation that decayed exponentially with a time constant tau= 4.6 +/-
      2.6 s (mean +/- standard deviation). When the trains were repeated at 1-10 s
      intervals, augmentation markedly increased the size of the first EPSCs, leaving
      late EPSCs unaffected. The magnitude of augmentation was dependent on the number
      of pulses, pulse rate and intervals between trains. Augmented EPSCs changed
      proportionally to basal EPSC amplitudes following alterations in extracellular
      calcium ion concentration. The results indicate that augmentation is determined
      by residual calcium remaining in the presynaptic terminal after repetitive
      spikes, competing with fast facilitation. We propose that augmentation serves to
      maintain a high synaptic strength in the corticogeniculate positive feedback
      system during attentive visual exploration.

PMID- 14724204
TI  - Membrane cholesterol modulates dihydropyridine receptor function in mice fetal
      skeletal muscle cells.
AB  - Caveolae and transverse (T-) tubules are membrane structures enriched in
      cholesterol and glycosphingolipids. They play an important role in receptor
      signalling and myogenesis. The T-system is also highly enriched in
      dihydropyridine receptors (DHPRs), which control excitation-contraction (E-C)
      coupling. Recent results have shown that a depletion of membrane cholesterol
      alters caveolae and T-tubules, yet detailed functional studies of DHPR expression
      are lacking. Here we studied electrophysiological and morphological effects of
      methyl-beta-cyclodextrin (MbetaCD), a cholesterol-sequestering drug, on freshly
      isolated fetal skeletal muscle cells. Exposure of fetal myofibres to 1-3 mM
      MbetaCD for 1 h at 37 degrees C led to a significant reduction in caveolae and T
      tubule areas and to a decrease in cell membrane electrical capacitance. In whole
      cell voltage-clamp experiments, the L-type Ca(2+) current amplitude was
      significantly reduced, and its voltage dependence was shifted approximately 15 mV
      towards more positive potentials. Activation and inactivation kinetics were
      slower in treated cells than in control cells and stimulation by a saturating
      concentration of Bay K 8644 was enhanced. In addition, intramembrane charge
      movement and Ca(2+) transients evoked by a depolarization were reduced without a
      shift of the midpoint, indicating a weakening of E-C coupling. In contrast, T
      type Ca(2+) current was not affected by MbetaCD treatment. Most of the L-type
      Ca(2+) conductance reduction and E-C coupling weakening could be explained by a
      decrease of the number of DHPRs due to the disruption of caveolae and T-tubules.
      However, the effects on L-type channel gating kinetics suggest that membrane
      cholesterol content modulates DHPR function. Moreover, the significant shift of
      the voltage dependence of L-type current without any change in the voltage
      dependence of charge movement and Ca(2+) transients suggests that cholesterol
      differentially regulates the two functions of the DHPR.

PMID- 14724205
TI  - Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes
      with controlled SR Ca2+ load and Ca2+ current trigger.
AB  - Cardiac Ca(2+) transients are enhanced by cAMP-dependent protein kinase (PKA).
      However, PKA-dependent modulation of ryanodine receptor (RyR) function in intact
      cells is difficult to measure, because PKA simultaneously increases Ca(2+)
      current (I(Ca)), SR Ca(2+) uptake and SR Ca(2+) loading (which independently
      increase SR Ca(2+) release). We measured I(Ca) and SR Ca(2+) release +/- 1 microm
      isoproterenol (ISO; isoprenaline) in voltage-clamped ventricular myocytes of
      rabbits and transgenic mice (expressing only non-phosphorylatable phospholamban).
      This mouse model helps control for any effect of ISO-enhanced SR uptake on
      observed release, but the two species produced essentially identical results. SR
      Ca(2+) load and I(Ca) were adjusted by conditioning. We thus evaluated PKA
      effects on SR Ca(2+) release at constant SR Ca(2+) load and I(Ca) trigger (with
      constant unitary I(Ca)). The amount of SR Ca(2+) release increased as a function
      of either I(Ca) or SR Ca(2+) load, but ISO did not alter the relationships
      (measured as gain or fractional release). This was true over a wide range of SR
      Ca(2+) load and I(Ca). However, the maximal rate of SR Ca(2+) release was
      approximately 50% faster with ISO (at most loads and I(Ca) levels). We conclude
      that the isolated effect of PKA on SR Ca(2+) release is an increase in maximal
      rate of release and faster turn-off of release (such that integrated SR Ca(2+)
      release is unchanged). The increased amount of SR Ca(2+) release normally seen
      with ISO depends primarily on increased I(Ca) trigger and SR Ca(2+) load, whereas
      faster release kinetics may be the main result of RyR phosphorylation.

PMID- 14724206
TI  - Two modes of polyamine block regulating the cardiac inward rectifier K+ current
      IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line.
AB  - The strong inward rectifier K(+) current, I(K1), shows significant outward
      current amplitude in the voltage range near the reversal potential and thereby
      causes rapid repolarization at the final phase of cardiac action potentials.
      However, the mechanism that generates the outward I(K1) is not well understood.
      We recorded currents from the inside-out patches of HEK 293T cells that express
      the strong inward rectifier K(+) channel Kir2.1 and studied the blockage of the
      currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The
      outward current-voltage (I-V) relationships of Kir2.1, obtained with 5-10 microm
      spermine or 10-100 microm spermidine, were similar to the steady-state outward I
      V relationship of I(K1), showing a peak at a level that is approximately 20 mV
      more positive than the reversal potential, with a negative slope at more positive
      voltages. The relationships exhibited a plateau or a double-hump shape with 1
      microm spermine/spermidine or 0.1 microm spermine, respectively. In the chord
      conductance-voltage relationships, there were extra conductances in the positive
      voltage range, which could not be described by the Boltzmann relations fitting
      the major part of the relationships. The extra conductances, which generated most
      of the outward currents in the presence of 5-10 microm spermine or 10-100 microm
      spermidine, were quantitatively explained by a model that considered two
      populations of Kir2.1 channels, which were blocked by polyamines in either a high
      affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis
      of the inward tail currents following test pulses indicated that the relief from
      the spermine block of Kir2.1 consisted of an exponential component and a
      virtually instantaneous component. The fractions of the two components nearly
      agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the
      model. The estimated proportion of Mode 1 channels to total channels was 0.9 with
      0.1-10 microm spermine, 0.75 with 1-100 microm spermidine, and between 0.75 and
      0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine
      with the channel at an intracellular site appeared to modify the equilibrium of
      the two conformational channel states that allow different modes of blockage. Our
      results suggest that the outward I(K1) is primarily generated by channels with
      lower affinities for polyamines. Polyamines may regulate the amplitude of the
      outward I(K1), not only by blocking the channels but also by modifying the
      proportion of channels that show different sensitivities to the polyamine block.

PMID- 14724207
TI  - Exercise and nitric oxide prevent bubble formation: a novel approach to the
      prevention of decompression sickness?
AB  - Nitrogen dissolves in the blood during dives, but comes out of solution if divers
      return to normal pressure too rapidly. Nitrogen bubbles cause a range of effects
      from skin rashes to seizures, coma and death. It is believed that these bubbles
      form from bubble precursors (gas nuclei). Recently we have shown that a single
      bout of exercise 20 h, but not 48 h, before a simulated dive prevents bubble
      formation and protects rats from severe decompression sickness (DCS) and death.
      Furthermore, we demonstrated that administration of N(omega)-nitro-l-arginine
      methyl ester, a non-selective inhibitor of NO synthase (NOS), turns a dive from
      safe to unsafe in sedentary but not exercised rats. Therefore based upon previous
      data an attractive hypothesis is that it may be possible to use either exercise
      or NO-releasing agents before a dive to inhibit bubble formation and thus protect
      against DCS. Consequently, the aims of the present study were to determine
      whether protection against bubble formation in 'diving' rats was provided by (1)
      chronic and acute administration of a NO-releasing agent and (2) exercise less
      than 20 h prior to the dive. NO given for 5 days and then 20 h prior to a dive to
      700 kPa lasting 45 min breathing air significantly reduced bubble formation and
      prevented death. The same effect was seen if NO was given only 30 min before the
      dive. Exercise 20 h before a dive suppressed bubble formation and prevented
      death, with no effect at any other time (48, 10, 5 and 0.5 h prior to the dive).
      Pre-dive activities have not been considered to influence the growth of bubbles
      and thus the risk of serious DCS. The present novel findings of a protective
      effect against bubble formation and death by appropriately timed exercise and an
      NO-releasing agent may form the basis of a new approach to preventing serious
      decompression sickness.

PMID- 14724208
TI  - Effects of cytosolic NADH/NAD(+) levels on sarcoplasmic reticulum Ca(2+) release
      in permeabilized rat ventricular myocytes.
AB  - In the heart ischaemic conditions induce metabolic changes known to have profound
      effects on Ca(2+) signalling during excitation-contraction coupling. Ischaemia
      also affects the redox state of the cell. However, the role of cytosolic redox
      couples, such as the NADH/NAD(+) redox system, for the regulation of Ca(2+)
      homeostasis has remained elusive. We studied the effects of NADH and NAD(+) on
      sarcoplasmic reticulum (SR) Ca(2+) release in permeabilized rat ventricular
      myocytes as well as on Ca(2+) uptake by SR microsomes and ryanodine receptor
      (RyR) single channel activity. Exposure of permeabilized myocytes to NADH (2 mm;
      [Ca(2+)](cyt)= 100nm) decreased the frequency and the amplitude of spontaneous
      Ca(2+) sparks by 62% and 24%, respectively. This inhibitory effect was reversed
      by NAD(+) (2 mm) and did not depend on mitochondrial function. The inhibition of
      Ca(2+) sparks by NADH was associated with a 52% decrease in SR Ca(2+) load. Some
      of the effects observed with NADH may involve the generation of superoxide anion
      (O(2)(-).) as they were attenuated to just a transient decrease of Ca(2+) spark
      frequency by superoxide dismutase (SOD). O(2)(-). generated in situ from the
      xanthine/xanthine oxidase reaction caused a slowly developing decrease of Ca(2+)
      spark frequency and SR Ca(2+) load by 44% and 32%, respectively. Furthermore, in
      studies with cardiac SR microsomes NADH slowed the rate of ATP-dependent Ca(2+)
      uptake by 39%. This effect also appeared to depend on O(2)(-). formation. Single
      channel recordings from RyRs incorporated into lipid bilayers revealed that NADH
      (2 mm) inhibited the activity of RyR channels by 84%. However, NADH inhibition of
      RyR activity was O(2)(-).-independent. In summary, an increase of the cytoplasmic
      NADH/NAD(+) ratio depresses SR Ca(2+) release in ventricular cardiomyocytes. The
      effect appears to be mediated by direct NADH inhibition of RyR channel activity
      and by indirect NADH inhibition (O(2)(-). mediated) of SR Ca(2+)-ATPase activity
      with a subsequent decrease in SR Ca(2+) content.

PMID- 14724209
TI  - betaL-betaM loop in the C-terminal domain of G protein-activated inwardly
      rectifying K(+) channels is important for G(betagamma) subunit activation.
AB  - The activity of G protein-activated inwardly rectifying K(+) channels (GIRK or
      Kir3) is important for regulating membrane excitability in neuronal, cardiac and
      endocrine cells. Although G(betagamma) subunits are known to bind the N- and C
      termini of GIRK channels, the mechanism underlying G(betagamma) activation of
      GIRK is not well understood. Here, we used chimeras and point mutants constructed
      from GIRK2 and IRK1, a G protein-insensitive inward rectifier, to determine the
      region within GIRK2 important for G(betagamma) binding and activation. An
      analysis of mutant channels expressed in Xenopus oocytes revealed two amino acid
      substitutions in the C-terminal domain of GIRK2, GIRK2(L344E) and GIRK2(G347H),
      that exhibited decreased carbachol-activated currents but significantly enhanced
      basal currents with coexpression of G(betagamma) subunits. Combining the two
      mutations (GIRK2(EH)) led to a more severe reduction in carbachol-activated and
      G(betagamma)-stimulated currents. Ethanol-activated currents were normal,
      however, suggesting that G protein-independent gating was unaffected by the
      mutations. Both GIRK2(L344E) and GIRK2(EH) also showed reduced carbachol
      activation and normal ethanol activation when expressed in HEK-293T cells. Using
      epitope-tagged channels expressed in HEK-293T cells, immunocytochemistry showed
      that G(betagamma)-impaired mutants were expressed on the plasma membrane,
      although to varying extents, and could not account completely for the reduced
      G(betagamma) activation. In vitro G(betagamma) binding assays revealed an
      approximately 60% decrease in G(betagamma) binding to the C-terminal domain of
      GIRK2(L344E) but no statistical change with GIRK2(EH) or GIRK2(G347H), though
      both mutants exhibited G(betagamma)-impaired activation. Together, these results
      suggest that L344, and to a lesser extent, G347 play an important functional role
      in G(betagamma) activation of GIRK2 channels. Based on the 1.8 A structure of
      GIRK1 cytoplasmic domains, L344 and G347 are positioned in the betaL-betaM loop,
      which is situated away from the pore and near the N-terminal domain. The results
      are discussed in terms of a model for activation in which G(betagamma) alters the
      interaction between the betaL-betaM loop and the N-terminal domain.

PMID- 14724210
TI  - Opioid receptor stimulation suppresses the adrenal medulla hypoxic response in
      sheep by actions on Ca(2+) and K(+) channels.
AB  - Before the preganglionic regulation of the adrenal medulla is established,
      hypoxia acts directly on the chromaffin cells to evoke the secretion of
      catecholamines. This direct action of hypoxia is suppressed by the gradual
      development of the preganglionic innervation and we have proposed that opioid
      peptides released from the adrenal splanchnic nerves may be responsible for this
      suppression. The effects of the specific opioid agonists DPDPE (delta-agonist), U
      62066 (kappa-agonist) and DALDA (mu-agonist) on the hypoxia-evoked response were
      investigated in both a whole-gland preparation and in isolated adrenal chromaffin
      cells using amperometry, whole-cell patch clamping and measurement of cytosolic
      [Ca(2+)]. The combined application of mu- and kappa-type agonists abolished the
      hypoxia-evoked catecholamine secretion from whole perfused adrenal gland. In
      isolated chromaffin cells, mu- and kappa-opioid agonists reduced the rise in
      [Ca(2+)](i) that results from exposure to hypoxia. Both agonists decreased the
      voltage-dependent Ca(2+) current in these cells. The mu-agonist increased the
      conductance through SK-type K(+) channels and this action offset the decrease in
      K(+) conductance produced by exposure to hypoxia. The kappa-type agonist
      decreased the conductance through an action on BK-type K(+) channels, a class of
      channels that are not involved in initiating the direct response to hypoxia.
      These data suggest that opioids, through their action on SK channels and voltage
      dependent Ca(2+) channels, may be responsible for the nerve-induced suppression
      of the hypoxic response of adrenal chromaffin cells and that these effects of
      endogenous opioids are mediated via mu- and kappa-type receptors.

PMID- 14724211
TI  - Creatine supplementation increases glucose oxidation and AMPK phosphorylation and
      reduces lactate production in L6 rat skeletal muscle cells.
AB  - Recent observations have suggested that creatine supplementation might have a
      beneficial effect on glucoregulation in skeletal muscle. However, conclusive
      studies on the direct effects of creatine on glucose uptake and metabolism are
      lacking. The objective of this study was to investigate the effects of creatine
      supplementation on basal and insulin-stimulated glucose transporter (GLUT4)
      translocation, glucose uptake, glycogen content, glycogen synthesis, lactate
      production, glucose oxidation and AMP-activated protein kinase (AMPK)
      phosphorylation in L6 rat skeletal muscle cells. Four treatment groups were
      studied: control, insulin (100 nM), creatine (0.5 mM) and creatine + insulin.
      After 48 h of creatine supplementation the creatine and phosphocreatine contents
      of L6 myoblasts increased by approximately 9.3- and approximately 5.1-fold,
      respectively, but the ATP content of the cells was not affected. Insulin
      significantly increased 2-deoxyglucose uptake ( approximately 1.9-fold), GLUT4
      translocation ( approximately 1.8-fold), the incorporation of D-[U-(14)C]glucose
      into glycogen ( approximately 2.3-fold), lactate production ( approximately 1.5
      fold) and (14)CO(2) production ( approximately 1.5-fold). Creatine neither
      altered the glycogen and GLUT4 contents of the cells nor the insulin-stimulated
      rates of 2-DG uptake, GLUT4 translocation, glycogen synthesis and glucose
      oxidation. However, creatine significantly reduced by approximately 42% the basal
      rate of lactate production and increased by approximately 40% the basal rate of
      (14)CO(2) production. This is in agreement with the approximately 35% increase in
      citrate synthase activity and also with the approximately 2-fold increase in the
      phosphorylation of both alpha-1 and alpha-2 isoforms of AMPK after creatine
      supplementation. We conclude that 48 h of creatine supplementation does not alter
      insulin-stimulated glucose uptake and glucose metabolism; however, it activates
      AMPK, shifts basal glucose metabolism towards oxidation and reduces lactate
      production in L6 rat skeletal muscle cells.

PMID- 14724212
TI  - Effect of gastric distension on cardiovascular parameters: gastrovascular reflex
      is attenuated in the elderly.
AB  - Stretching the stomach wall in young healthy subjects causes an increase in
      muscle sympathetic nerve activity and in blood pressure, the gastrovascular
      reflex. We compared healthy elderly subjects with healthy young subjects to find
      out whether the gastrovascular reflex attenuates in normal ageing and we studied
      whether there was a difference in autonomic function or gastric compliance that
      could explain this possible attenuation. Muscle sympathetic nerve activity,
      finger blood pressure and heart rate were continuously recorded during stepwise
      isobaric gastric distension using a barostat in eight healthy young (6 men and 2
      women, 27 +/- 3.2 years, mean +/-s.e.m.) and eight healthy elderly subjects (7
      men and 1 woman, 76 +/- 1.5 years). Changes in cardiac output and total
      peripheral arterial resistance were calculated from the blood pressure signal.
      The baseline mean arterial pressure and muscle sympathetic nerve activity were
      higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity
      increase during the cold pressor test was lower in the elderly group (P = 0.005).
      During stepwise gastric distension, the elderly subjects showed an attenuated
      increase in muscle sympathetic nerve activity compared to the young subjects (P <
      0.01). The older group tended to show a higher increase in mean arterial pressure
      (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P =
      0.09) The cardiac output rose slightly in both groups without significant
      difference between groups. The fundic compliance did not differ between groups.
      We conclude that stepwise gastric distension caused an increase in muscle
      sympathetic nerve activity in both groups, but the increase in the elderly was
      attenuated.

PMID- 14724213
TI  - Developmental regulation of the 5-HT7 serotonin receptor and transcription factor
      NGFI-A in the fetal guinea-pig limbic system: influence of GCs.
AB  - Fetal exposure to excess glucocorticoids (GCs) programs the developing
      hypothalamo-pituitary-adrenal (HPA) axis, and may predispose offspring to adult
      onset disease. During development, serotonin (5-HT) influences transcription of
      hippocampal GR mRNA via the 5-HT7 receptor. The effect of 5-HT on GR involves the
      transcription factor NGFI-A. Given the developmental changes which we have
      previously reported in hippocampal GR mRNA expression, we hypothesized that (1)
      there are progressive developmental changes in 5-HT7 receptor and NGFI-A mRNA
      expression in the fetal guinea-pig limbic system, and (2) repeated exposure to
      synthetic GC treatment will significantly modify developmental expression of
      these genes. 5-HT7 receptor mRNA was highly expressed in the hippocampus and
      thalamus at gestational day (gd) 40 (term approximately 70 days), and
      significantly decreased (P < 0.05) with advancing gestation. Conversely, NGFI-A
      mRNA expression in the hippocampus and frontal cortex was almost undetectable at
      gd40, but was dramatically elevated (P < 0.05; 8-fold) near term. Changes in mRNA
      were refelected by NGFI-A protein levels. These changes were significantly
      correlated to hippocampal GR expression and fetal plasma cortisol concentrations.
      Synthetic GC treatment increased NGFI-A mRNA levels in CA1 and the cingulate
      cortex, but had no effect on 5-HT7 receptor expression. In conclusion our results
      suggest that (1) limbic 5-HT7 receptor expression is not directly linked to
      maturation of hippocampal GR in late gestation; (2) the up-regulation of NGFI-A
      expression near term is driven by glucocorticoid; and (3) premature exposure to
      synthetic glucocorticoid significantly increases NGFI-A-related transcriptional
      activity in the fetal limbic system.

PMID- 14724214
TI  - Five basic muscle activation patterns account for muscle activity during human
      locomotion.
AB  - An electromyographic (EMG) activity pattern for individual muscles in the gait
      cycle exhibits a great deal of intersubject, intermuscle and context-dependent
      variability. Here we examined the issue of common underlying patterns by applying
      factor analysis to the set of EMG records obtained at different walking speeds
      and gravitational loads. To this end healthy subjects were asked to walk on a
      treadmill at speeds of 1, 2, 3 and 5 kmh(-1) as well as when 35-95% of the body
      weight was supported using a harness. We recorded from 12-16 ipsilateral leg and
      trunk muscles using both surface and intramuscular recording and determined the
      average, normalized EMG of each record for 10-15 consecutive step cycles. We
      identified five basic underlying factors or component waveforms that can account
      for about 90% of the total waveform variance across different muscles during
      normal gait. Furthermore, while activation patterns of individual muscles could
      vary dramatically with speed and gravitational load, both the limb kinematics and
      the basic EMG components displayed only limited changes. Thus, we found a
      systematic phase shift of all five factors with speed in the same direction as
      the shift in the onset of the swing phase. This tendency for the factors to be
      timed according to the lift-off event supports the idea that the origin of the
      gait cycle generation is the propulsion rather than heel strike event. The basic
      invariance of the factors with walking speed and with body weight unloading
      implies that a few oscillating circuits drive the active muscles to produce the
      locomotion kinematics. A flexible and dynamic distribution of these basic
      components to the muscles may result from various descending and proprioceptive
      signals that depend on the kinematic and kinetic demands of the movements.

PMID- 14724215
TI  - Differential cytokine response in interstitial fluid in skin and serum during
      experimental inflammation in rats.
AB  - Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are
      important mediators produced during inflammation. We hypothesized that the pro
      inflammatory cytokine response in the interstitial fluid (IF) is different from
      that in serum, and we aimed at quantifying the amount of TNF-alpha and IL-1beta
      in the IF. By centrifugation of rat skin at < 424 g pure IF is extracted. Using
      ELISA such fluid was analysed for cytokines in back and/or paw skin of
      pentobarbital-anaesthetized rats, after either induction of endotoxaemia or
      ischaemia-reperfusion (I/R) injury. During endotoxaemia, TNF-alpha increased in
      the IF from 0 in control to 640 +/- 100 pg ml(-1) (mean +/-s.e.m.) after 90 min,
      with the serum concentration being 5-10 times higher at all time points. The
      response pattern of IL-1beta after lipopolysaccharide (LPS) challenge differed
      greatly from that of TNF-alpha with a large increase in IF from 390 +/- 90 to 28
      000 +/- 1500 pg ml(-1) after 210 min, and a significantly smaller increase in
      serum (600 +/- 45 pg ml(-1)). During reperfusion of the hind paw after 2 h of
      ischaemia, there was a gradual increase of TNF-alpha in both IF of the paw skin
      and serum after 3 min of reperfusion. Both declined after 20 min. The pattern for
      IL-1beta differed, increasing significantly less in serum (25 +/- 15 pg ml(-1)
      after 20 min of reperfusion) than in the IF (1100 +/- 200 pg ml(-1)).
      Immunostaining of the inflamed tissues showed increased expression of the two
      cytokines in cells of both epidermis and dermis compared to controls. Subdermal
      injections of TNF-alpha and IL-1beta at the same concentrations found in IF after
      LPS infusion affected interstitial fluid pressure significantly. Local TNF-alpha
      production dominates after I/R injury, whereas in endotoxaemia systemic
      production predominates. For IL-1beta local production dominates in both
      conditions. Thus, there is a differential pattern of cytokine production and the
      current method allows the study of the role of cytokines in IF during different
      inflammatory reactions.

PMID- 14724216
TI  - Intracellular Ca2+ and pacemaking within the rabbit sinoatrial node:
      heterogeneity of role and control.
AB  - Recent studies have proposed that release of calcium from the sarcoplasmic
      reticulum (SR) modulates the spontaneous activity of the sinoatrial node (SAN).
      Previously we have shown that several calcium regulatory proteins are expressed
      at a lower level in the centre of the SAN compared with the periphery. Such
      differences may produce heterogeneity of intracellular calcium handling and
      pacemaker activity across the SAN. Selective isolations showed that the centre of
      the SAN is composed of smaller cells than the periphery. Measurements of
      cytosolic calcium in spontaneously beating cells showed that diastolic calcium,
      systolic calcium, the calcium transient amplitude and spontaneous rate were
      greater in larger (likely to be peripheral) cells compared with smaller (likely
      to be central) SAN cells. The SR calcium content was greater in larger cells,
      although SR recruitment was more efficient in smaller cells. The sodium-calcium
      exchanger and sarcolemmal calcium ATPase had a lower activity and the exchanger
      was responsible for a larger proportion of sarcolemmal calcium extrusion in
      smaller cells compared with larger cells. Ryanodine had a greater effect on the
      spontaneous calcium transient in larger cells compared with smaller cells, and
      slowed pacemaker activity in larger cells but not smaller cells, thus abolishing
      the difference in cycle length. This study shows heterogeneity of intracellular
      calcium regulation within the SAN and this contributes to differences in
      pacemaker activity between cells from across the SAN. The smallest central cells
      of the leading pacemaker region of the SAN do not require SR calcium for
      spontaneous activity nor does disruption of the SR alter pacemaking in these
      primary pacemaker cells.

PMID- 14724217
TI  - Methylphenidate restores ventral tegmental area dopamine neuron activity in
      prenatal ethanol-exposed rats by augmenting dopamine neurotransmission.
AB  - Altered neurotransmission in the mesolimbic dopamine (DA) system has been
      suggested to be the underlying cause of attention problems commonly observed in
      children with fetal alcohol spectrum disorder (FASD). Methylphenidate is
      effective in treating attention problems in children with FASD. However, the
      underlying mechanism is currently unknown. We have shown previously that reduced
      ventral tegmental area (VTA) DA neuron activity in prenatal ethanol-exposed
      animals can be normalized by DA agonist treatment. In the present study, we
      investigated the possibility that similar mechanism mediates the effect of
      methylphenidate using the in vivo extracellular single-unit recording technique
      in anesthetized animals. We observed that reduced VTA DA neuron activity in
      prenatal ethanol-exposed animals was normalized by methylphenidate. The effect of
      methylphenidate was mediated by increased extracellular levels of DA instead of
      norepinephrine because this effect was not altered by the coadministration of
      prazosin, an alpha(1) receptor antagonist, and was mimicked by the application of
      DA transporter blockers, nomifensine and 1-2(-[bis(4-flurophenyl)methoxy]ethyl)-4
      (3-phenyl)piperazine dihydrochloride (GBR 12909). These observations support our
      hypothesis that depolarization inactivation is the cause of prenatal ethanol
      exposure-induced reduction in VTA DA neuron activity. We speculate that
      methylphenidate normalized the activity of VTA DA neurons by increasing
      extracellular DA levels in the VTA and the activation of somatodendritic DA
      autoreceptors. As a result, the depolarization inactivation was removed by
      hyperpolarization. The normalized VTA DA neuron activity in prenatal ethanol
      exposed animals may contribute to a restoration of DA neurotransmission and the
      therapeutic effect of methylphenidate in attention problems in children with
      FASD.

PMID- 14724218
TI  - Intrinsic cytotoxicity and chemomodulatory actions of novel
      phenethylisothiocyanate sphingoid base derivatives in HL-60 human promyelocytic
      leukemia cells.
AB  - The protein kinase C (PKC) isoenzyme superfamily represents a popular target in
      pharmacological interventions designed to elicit apoptosis directly in tumor
      cells or to potentiate the lethal effects of antineoplastic agents. Numerous
      observations support the clinical utility of PKC inhibition by experimental
      sphingolipid derivatives such as safingol. The present studies document the
      cytotoxicity and chemomodulatory capacity of phenethylisothiocyanate derivatives
      of sphinganine and sphingosine (PEITC-Sa and PEITC-So) in the human myeloid
      leukemia cell line HL-60. The biological actions of these novel derivatives were
      compared directly with those of the parent compounds sphinganine and sphingosine.
      Exposure to natural and modified sphingoid bases promoted extensive apoptotic
      cell death. The PEITC-sphingoid base derivatives exhibited higher cytotoxicity
      than their natural counterparts and were also distinctly superior to the
      clinically relevant sphingoid base analog safingol. In each instance, lethality
      was shown to correlate with inhibition of conventional and novel PKC isoforms and
      downstream loss of extracellular signal-regulated kinase (ERK)1/ERK2. The
      involvement of these signaling systems in potentiating the lethal actions of 1
      (beta-D-arabinofuranosyl)cytosine (araC) was also examined with regard to the
      differential actions of PEITC-Sa and PEITC-So to that of the parent compounds as
      well as safingol. Exposure to araC alone rapidly increased PKC activity. In the
      presence of PEITC-Sa or PEITC-So, the therapeutic efficacy of araC increased
      markedly; moreover, potentiation was directly related to the loss of araC
      stimulated PKC activity. These findings demonstrate that PEITC-substituted
      sphingoid base analogs exert potent antineoplastic effects in human leukemia
      cells. We suggest that these synthetic lipids represent potentially useful agents
      in the development of conventional PKC/novel PKC-directed chemotherapeutic
      strategies.

PMID- 14724219
TI  - Pulse of nitric oxide release in response to activation of N-methyl-D-aspartate
      receptors in the rat striatum: rapid desensitization, inhibition by receptor
      antagonists, and potentiation by glycine.
AB  - Increased activity of glutamate N-methyl-d-aspartate (NMDA) receptors is the
      dominant mechanism by which nitric oxide (NO.) is generated. By using a selective
      direct-current amperometry method, we characterized real time NO* release in vivo
      in response to chemical stimulation of NMDA receptors in the rat striatum. The
      application of NMDA caused the appearance of a sharp and transient oxidation
      signal. Concentration-response studies (10-500 microM) indicated an EC(50) of 48
      microM. The NMDA-induced amperometric signal was suppressed by focal application
      of the nitric-oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME, 100
      microM) or D-(-)-2-amino-5-phosphonopentanoic acid (AP-5, 100 microM) or by
      systemic injection of dizocilpine (1 mg/kg i.p.), drugs that, when given alone,
      had no effect on baseline oxidation current. Repeated injections of NMDA at short
      intervals (approximately 80 s) resulted in a progressive reduction of the
      amperometric signal with a decay half-life of 1.36 min. Sixty min after the last
      NMDA application the amperometric response was restored to initial levels.
      Finally, the coapplication of glycine (50 or 100 microM), which, when given alone
      had no effect, potentiated the NMDA-induced response. Thus, NMDA receptor
      mediated activation of striatal NO* system shuts off quickly and undergoes rapid
      desensitization, suggesting a feedback inhibition of NMDA receptor function. To
      the extent of NO* release can represent a correlate of NMDA receptor activity,
      its amperometric detection could be useful to assess in vivo the state of
      excitatory transmission under physiological, pharmacological, or pathological
      conditions.

PMID- 14724220
TI  - Cyclohexyl-octahydro-pyrrolo[1,2-a]pyrazine-based inhibitors of human N
      myristoyltransferase-1.
AB  - N-myristoyltransferase (NMT) is an emerging therapeutic target that catalyzes the
      attachment of myristate to the N terminus of an acceptor protein. We have
      developed a medium-throughput assay for screening potential small molecule
      inhibitors of human NMT-1 consisting of recombinant enzyme, biotinylated peptide
      substrate, and [3H]myristoyl-CoA. Approximately 16,000 diverse compounds have
      been evaluated, and significant inhibition of NMT was found with 0.8% of the
      compounds. From these hits, we have identified the cyclohexyl
      octahydropyrrolo[1,2-a]pyrazine (COPP) chemotype as inhibitory toward human NMT
      1. Thirty-two compounds containing this substructure inhibited NMT-1, with IC(50)
      values ranging from 6 microM to millimolar concentrations, and a quantitative
      structure-activity relationship equation (r(2) = 0.72) was derived for the
      series. The most potent inhibitor (24, containing 9-ethyl-9H-carbazole)
      demonstrated competitive inhibition for the peptide-binding site of NMT-1 and
      noncompetitive inhibition for the myristoyl-CoA site. Computational docking
      studies using the crystal structure of the highly homologous yeast NMT confirmed
      that 24 binds with excellent complementarity to the peptide-binding site of the
      enzyme. To evaluate the ability of 24 to inhibit NMT activity in intact cells,
      monkey CV-1 cells expressing an N-myristoylated green fluorescent protein (GFP)
      fusion protein were treated with a known NMT inhibitor or with 24. Each compound
      caused the redistribution of GFP from the plasma membrane to the cytosol.
      Furthermore, 24 inhibits cancer cell proliferation at doses similar to those that
      inhibit protein myristoylation. Overall, these studies establish an efficient
      assay for screening for inhibitors of human NMT and identify a novel family of
      inhibitors that compete at the peptide-binding site and have activity in intact
      cells.

PMID- 14724221
TI  - Inhibition of oxidant-induced nuclear factor-kappaB activation and inhibitory
      kappaBalpha degradation and instability of F-actin cytoskeletal dynamics and
      barrier function by epidermal growth factor: key role of phospholipase-gamma
      isoform.
AB  - Using monolayers of intestinal (Caco-2) cells as a model for studying
      inflammatory bowel disease (IBD), we previously showed that nuclear factor-kappaB
      (NF-kappaB) activation is required for oxidant-induced disruption of cytoskeletal
      and barrier integrity. Epidermal growth factor (EGF) stabilizes the F-actin
      cytoskeleton and protects against oxidant damage, but the mechanism remains
      unclear. We hypothesized that the mechanism involves activation of phospholipase
      C-gamma (PLC-gamma), which prevents NF-kappaB activation and the consequences of
      this activation, namely, cytoskeletal and barrier disruption. We studied wild
      type and transfected cells. The latter were transfected with varying levels (1-5
      microg) of cDNA to either stably overexpress PLC-gamma or to inhibit its
      activation. Cells were pretreated with EGF before exposure to oxidant (H(2)O(2)).
      Stably overexpressing PLC-gamma (+2.0-fold) or preincubating with EGF protected
      against oxidant injury as indicated by 1) decreases in several NF-kappaB-related
      variables [NF-kappaB (p50/p65 subunit) nuclear translocation, NF-kappaB subunit
      activity, inhibitory-kappaBalpha (I-kappaBalpha) phosphorylation and
      degradation]; 2) increases in F-actin and decreases in G-actin; 3) stabilization
      of the actin cytoskeletal architecture; and 4) enhancement of barrier function.
      Overexpression induced inactivation of NF-kappaB was potentiated by EGF. PLC
      gamma was found mostly in membrane and cytoskeletal fractions (<9% in the
      cytosolic fractions), indicating its activation. Dominant negative inhibition of
      endogenous PLC-gamma (-99%) substantially prevented all measures of EGF
      protection against NF-kappaB activation. We concluded 1) EGF protects against
      oxidant-induced barrier disruption through PLC-gamma activation, which
      inactivates NF-kappaB; 2) Activation of PLC-gamma by itself is protective against
      NF-kappaB activation; 3) the ability to modulate the dynamics of NF-kappaB/I
      kappa Balpha is a novel mechanism not previously attributed to the PLC family of
      isoforms in cells; and 4) development of PLC-gamma mimetics represents a possible
      new therapeutic strategy for IBD.

PMID- 14724222
TI  - Characterization of the contractile 5-hydroxytryptamine receptor in the renal
      artery of the normotensive rat.
AB  - Our goal was to characterize the 5-hydroxytryptamine (5-HT) receptor(s) mediating
      contraction in the isolated right renal artery, testing the hypothesis that the 5
      HT(2A) receptor would be the primary and likely only 5-HT receptor involved in
      contraction. Contraction of arteries was investigated in isolated tissue baths,
      and expression of 5-HT receptors was measured using immunohistochemical and
      Western analyses. Compared with endothelium-denuded rat aorta, a tissue with an
      established 5-HT(2A) receptor, endothelium-denuded renal artery contracted to 5
      HT with a 10-fold greater potency. Surprisingly, the 5-HT(2B) receptor agonist
      alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine hydrochloride (BW723C86)
      caused a concentration-dependent contraction that was antagonized by the 5-HT(2B)
      receptor antagonist 6-methyl-1,2,3,4-tetrahydro-1-[3,4-dimethoxyphenyl) methyl-9H
      pyrido[3,4b]indole] hydrochloride (LY272015) and nonselective 5-HT(2) receptor
      antagonist 6-methyl-1-(1-methylethyl)-ergoline-8b-carboxylic acid 2-hydroxy-1
      methylpropyl ester maleate (LY53857). Correlation of -log EC(50) values with
      binding affinities (pK(i)) indicated that contraction of the renal artery
      elicited by 13 different agonists was likely consistent with activation of a 5
      HT(2A) (r = 0.928) and 5-HT(2B) (r = 0.843) receptor. 5-HT-induced contraction
      was shifted by the 5-HT(2A) receptor antagonist ketanserin (3 and 10 nM) and the
      5-HT(2B) receptor antagonist LY272015 (10 and 50 nM). Higher than expected
      concentrations of the 5-HT(2A)/5-HT(2B) receptor antagonist LY53857 were needed
      to antagonize 5-HT-induced contraction and the 5-HT(2B) receptor antagonist 2
      amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine (RS127445) was virtually
      inactive. Western and immunohistochemical analyses of the renal artery validated
      the presence of 5-HT(2A) and 5-HT(2B) receptor protein. These results suggest
      that the renal artery possesses a complex 5-HT receptor population, including
      ketanserin- and LY272015-sensitive receptors. This unique pharmacology may
      reflect differences in 5-HT receptor coupling between tissues or heterogeneity in
      the subtype(s) of 5-HT receptors expressed in the renal artery.

PMID- 14724223
TI  - 5-Hydroxytryptamine1B receptor-mediated contraction of rabbit saphenous vein and
      basilar artery: role of vascular endothelium.
AB  - This study characterizes the sumatriptan-sensitive [5-hydroxytryptamine (5
      HT)(1B/1D)] receptor in rabbit saphenous vein and basilar artery. (S)-(-)-1-[2-[4
      (4-Methoxy-phenyl)-piperazin-1-yl]-ethyl]isochroman-6-carboxylic acid methylamide
      (PNU-109291), a 5-HT(1D) subtype-selective agonist (human K(i) = 2.5 +/- 0.07
      nM), did not contract either tissue, whereas o-methoxyphenylpiperazide derivative
      4F (MPPA-4F), a 5-HT(1B) subtype-selective antagonist (human K(i) = 4.6 +/- 0.6
      nM) potently inhibited sumatriptan-induced contraction in the saphenous vein and
      basilar artery. These results suggested that sumatriptan-induced contraction was
      mediated via the 5-HT(1B) receptor in these blood vessels. 5-HT(1B) receptor
      mediated contraction was then compared in endothelium-intact and denuded vessels
      to evaluate the role of the endothelium in regulating sumatriptan-induced
      contractility in these tissues. The presence of an intact endothelium inhibited 5
      HT(1B)-induced contraction in both tissues. Endothelial denudation or nitric
      oxide synthase inhibition with N(omega) nitro-L-arginine methyl ester (L-NAME)
      (100 microM) increased the efficacy and potency of sumatriptan in the saphenous
      vein and basilar artery. Surprisingly, in endothelial-denuded vascular tissues, L
      NAME (100 microM) also significantly increased the maximal 5-HT(1B) receptor
      induced contraction in both tissues, with no effect on potency of sumatriptan.
      The effect of L-NAME after endothelial denudation may reflect the presence of a
      low density of residual endothelial cells as estimated by CD31 antibody staining
      combined with the modulating effect of nitric oxide released from nonendothelial
      cells in vascular tissue. Endothelial modulation was specific to 5-HT(1B)
      receptors because removal of the endothelium did not significantly alter
      contraction to norepinephrine, histamine, prostaglandin, or potassium chloride in
      the saphenous vein or basilar artery.

PMID- 14724224
TI  - Comparison of pulmonary/nasal CYP2F expression levels in rodents and rhesus
      macaque.
AB  - Naphthalene is a ubiquitous environmental contaminant that results in dose
      dependent and tissue-, species-, and cell-selective necrosis of murine Clara
      cells upon exposure. Naphthalene is metabolized by CYP2F to a 1,2-epoxide, the
      first and obligate step in events leading to cytotoxicity. The studies reported
      here examine the relationship between levels of transcript (mRNA) and CYP2F
      protein in the respiratory tract of rodents with tissue susceptibility to injury.
      In both mice and rats, the lung contains more CYP2F transcript than liver; levels
      in kidney were undetectable. Mice expressed 4- and 8-fold greater CYP2F
      transcript in lung and liver tissue, respectively, than rats. Quantitative
      immunoblot blot analysis of CYP2F in airway subcompartments revealed mice to have
      30- (minor daughters/terminal bronchioles), 20- (major daughter), 40- (trachea),
      and 6- (parenchyma) fold higher levels of CYP2F protein than rats. Within the
      lungs of both rodent species, the highest CYP2F expression was found in the
      distal airways. The kidney contained undetectable amounts of CYP2F; multiple
      immunoreactive bands in liver precluded quantification. The olfactory epithelium
      contains the greatest amount of cytochrome P450 protein of all tissues studied in
      the rat, consistent with the observed pattern of in vivo injury. Overall, these
      studies in rodents demonstrate a strong association between CYP2F expression
      levels and susceptibility to naphthalene-induced cytotoxicity. Of all primate
      tissues studied, only the nasal ethmoturbinates contain quantifiable amounts of
      CYP2F, roughly 10- and 20-fold less than the corresponding tissues in rats and
      mice, respectively. These results suggest that rhesus macaques may be refractory
      to naphthalene-induced pulmonary injury.

PMID- 14724225
TI  - Primaquine-induced hemolytic anemia: susceptibility of normal versus glutathione
      depleted rat erythrocytes to 5-hydroxyprimaquine.
AB  - Primaquine is an important antimalarial agent because of its activity against
      exoerythrocytic forms of Plasmodium spp. Methemoglobinemia and hemolytic anemia,
      however, are dose-limiting side effects of primaquine therapy. These hemotoxic
      effects are believed to be mediated by metabolites, although the identity of the
      toxic specie(s) and the mechanism underlying hemotoxicity have remained unclear.
      Previous studies showed that an N-hydroxylated metabolite of primaquine, 6
      methoxy-8-hydroxylaminoquinoline, was capable of mediating primaquine-induced
      hemotoxicity. The present studies were undertaken to investigate the hemolytic
      potential of 5-hydroxyprimaquine (5-HPQ), a phenolic metabolite that has been
      detected in experimental animals. 5-HPQ was synthesized, isolated by flash
      chromatography, and characterized by NMR spectroscopy and mass spectrometry. In
      vitro exposure of (51)Cr-labeled erythrocytes to 5-HPQ induced a concentration
      dependent decrease in erythrocyte survival (TC(50) of ca. 40 microM) when the
      exposed cells were returned to the circulation of isologous rats. 5-HPQ also
      induced methemoglobin formation and depletion of glutathione (GSH) when incubated
      with suspensions of rat erythrocytes. Furthermore, when red cell GSH was depleted
      (>95%) by titration with diethyl maleate to mimic GSH instability in human
      glucose-6-phosphate dehydrogenase deficiency, a 5-fold enhancement of hemolytic
      activity was observed. These data indicate that 5-HPQ also has the requisite
      properties to contribute to the hemotoxicity of primaquine. The relative
      contribution of N-hydroxy versus phenolic metabolites to the overall hemotoxicity
      of primaquine remains to be assessed.

PMID- 14724226
TI  - Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39) after
      intranasal administration.
AB  - Exendin, a member of the glucagon-like peptide-1 family, and its antagonist
      exendin(9-39) affect cognition and neuronal survival after their intranasal
      delivery. Here, we examined the uptake of radioactively labeled exendin(9-39) (I
      Ex) by the olfactory bulbs, brain (minus pineal, pituitary, and olfactory bulb),
      cerebrospinal fluid, and cervical lymph nodes (C-node) as well as levels in serum
      after intranasal or intravenous administration. We found that olfactory bulb
      uptake of I-Ex after intranasal administration was rapid, much greater than after
      i.v. administration, and was enhanced by about 60% with cyclodextrin (CD). I-Ex
      was also taken up by the remainder of the brain after intranasal administration,
      but this uptake was not enhanced by CD, nor did it exceed uptake after i.v.
      administered I-Ex. Uptake by the olfactory bulb was not dependent on Brownian
      motion but did involve active processes. Intranasal I-Ex reached the C-node by
      way of the blood. About one-sixth of the intranasal dose of I-Ex entered the
      blood. However, the vascular route accounted for little of the intranasal I-Ex
      that reached the brain and even less that reached the olfactory bulb. I-Ex after
      intranasal administration was found in the hippocampus, cerebellum, brain stem,
      and cerebrospinal fluid (CSF). Distribution patterns showed that intranasal I-Ex
      used the extraneuronal route of CSF rather than brain parenchyma to diffuse
      throughout the brain. These results show that intranasal administration is an
      effective means of delivering peptide to the brain, especially the olfactory
      bulb.

PMID- 14724227
TI  - Activation of mu-opioid receptors inhibits synaptic inputs to spinally projecting
      rostral ventromedial medulla neurons.
AB  - The rostral ventromedial medulla (RVM) is a major locus for the descending
      control of nociception and opioid analgesia. However, it is not clear how opioids
      affect synaptic inputs to RVM neurons. In this study, we determined the effect of
      mu-opioid receptor activation on excitatory and inhibitory synaptic transmission
      in spinally projecting RVM neurons. RVM neurons were retrogradely labeled with a
      fluorescent tracer injected into the dorsal horn of the spinal cord in rats.
      Whole-cell voltage-clamp recordings were performed on labeled RVM neurons in
      brain slices in vitro. The mu-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]
      enkephalin (DAMGO, 1 microM) significantly decreased the amplitude of evoked
      excitatory postsynaptic currents (EPSCs) in 52% (9 of 17) of labeled cells. DAMGO
      also significantly reduced the amplitude of evoked inhibitory postsynaptic
      currents (IPSCs) in 69% (11 of 16) of cells examined. Furthermore, DAMGO
      significantly decreased the frequency of miniature EPSCs in 55% (15 of 27) of
      cells and significantly decreased the frequency of miniature IPSCs in all 12
      cells studied. Although most EPSCs and IPSCs were mediated by glutamate and GABA,
      the nicotinic and glycine receptor antagonists attenuated EPSCs and IPSCs,
      respectively, in some labeled RVM neurons. Immunocytochemical labeling revealed
      that only 35% of recorded RVM neurons were tryptophan hydroxylase-positive, and
      15% cells had GABA immunoreactivity. Thus, this study provides important
      functional evidence that activation of mu-opioid receptors decreases the release
      of both excitatory and inhibitory neurotransmitters onto most spinally projecting
      RVM neurons.

PMID- 14724228
TI  - The effects of vesicular volume on secretion through the fusion pore in
      exocytotic release from PC12 cells.
AB  - Many spikes in amperometric records of exocytosis events initially exhibit a
      prespike feature, or foot, which represents a steady-state flux of
      neurotransmitter through a stable fusion pore spanning both the vesicle and
      plasma membranes and connecting the vesicle lumen to the extracellular fluid.
      Here, we present the first evidence indicating that vesicular volume before
      secretion is strongly correlated with the characteristics of amperometric foot
      events. L-3,4-dihydroxyphenylalanine and reserpine have been used to increase and
      decrease, respectively, the volume of single pheochromocytoma cell vesicles.
      Amperometry and transmission electron microscopy have been used to determine that
      as vesicle size is decreased the frequency with which foot events are observed
      increases, the amount and duration of neurotransmitter released in the foot
      portion of the event decreases, and vesicles release a greater percentage of
      their total contents in the foot portion of the event. This previously
      unidentified correlation provides new insight into how vesicle volume can
      modulate the activity of the exocytotic fusion pore.

PMID- 14724229
TI  - Semaphorin3D guides retinal axons along the dorsoventral axis of the tectum.
AB  - We examined the role of Sema3D, a semaphorin of previously unknown function, in
      guiding retinal ganglion cell (RGC) axons to the optic tectum in the developing
      zebrafish. Sema3D is expressed more strongly in the ventral versus dorsal tectum,
      suggesting that it may participate in guiding RGC axons along the dorsoventral
      axis of the tectum. Ubiquitous misexpression of Sema3D in transgenic zebrafish
      inhibits ventral but not dorsal RGC axon growth. In addition, ventral RGC axons
      avoid or stop at individual cells misexpressing Sema3D along their pathway.
      Sema3D ubiquitous misexpression at later stages also causes ventral RGC axon
      arbors to spread more widely along the dorsoventral axis of the tectum. Knock
      down of Sema3D with morpholino antisense causes ventral RGC axons to extend
      aberrantly into the ventral tectum. These results suggest that Sema3D in the
      ventral tectum normally acts to inhibit ventral RGCs from extending into ventral
      tectum, ensuring their correct innervation of dorsal tectum.

PMID- 14724230
TI  - Activation of cAMP signaling facilitates the morphological maturation of newborn
      neurons in adult hippocampus.
AB  - Previous studies have demonstrated that activation of the cAMP cascade, including
      the cAMP response element-binding protein (CREB), increases the proliferation and
      survival of newborn neurons in adult mouse hippocampus. In the present study, we
      determined whether the cAMP-CREB cascade also influences the morphological
      maturation of newborn neurons in the subgranular zone of the hippocampus.
      Rolipram, a selective inhibitor of the cAMP-specific phosphodiesterase type 4,
      was administered to activate the cAMP cascade, and neuronal morphology was
      determined by analysis of Golgi-impregnated neurons in the subgranular zone of
      hippocampus. Rolipram administration significantly increased the number of branch
      points and length of dendrites relative to vehicle treatment. Increased branch
      number and length were accompanied by increased levels of phosphorylated CREB,
      the active form of this transcription factor, in immature neurons. In contrast,
      the morphology of Golgi-impregnated neurons was not significantly influenced by
      rolipram treatment in inducible transgenic mice expressing a dominant-negative
      mutant of CREB in hippocampus. We also tested the influence of cAMP analogs in
      primary hippocampal cultures and found that activation of the cAMP pathway
      increased and inhibition of the cAMP cascade decreased the number of branches and
      length of processes as observed in vivo. These findings indicate that the cAMP
      CREB cascade plays an important role in the differentiation and maturation of
      newborn neurons in hippocampus.

PMID- 14724231
TI  - Sodium channels and dendritic spike initiation at excitatory synapses in globus
      pallidus neurons.
AB  - Glutamatergic inputs from the subthalamic nucleus are suspected to provide a
      prominent source of excitation to globus pallidus (GP) neurons, despite their
      scarce number and mainly distal dendritic location. In this study we address the
      issue of whether dendritic sodium channels may facilitate the effect of
      excitatory inputs in GP. First, we examined the subcellular distribution of
      sodium channels using electron microscopic observations of immunoperoxidase and
      immunogold labeling. Voltage-gated sodium channels were found throughout GP
      dendrites and furthermore exhibited a specific clustering at sites of excitatory
      synaptic inputs. To examine the possibility that these channels could mediate
      dendritic spike generation, synaptic stimulation at visualized dendritic sites
      was performed during whole-cell recordings in vitro. These recordings revealed
      dendritic spike initiation in response to small excitatory inputs even for very
      distal stimulation sites. In contrast, subthreshold responses were mostly or
      fully attenuated at the soma for stimulation sites on distal dendrites. Computer
      simulations support the hypothesis that postsynaptic clustering of sodium
      channels allows dendritic triggering of spikes in response to inputs that would
      be too small to trigger a spike given uniformly distributed dendritic sodium
      channels. These findings indicate that postsynaptic sodium channel clustering is
      an effective mechanism to mediate a novel form of synaptic amplification and
      dendritic spike initiation. The ability of small amounts of excitation to trigger
      spikes in GP dendrites supports the prominent role of subthalamic input in the
      control of GP activity.

PMID- 14724232
TI  - Small clusters of electrically coupled neurons generate synchronous rhythms in
      the thalamic reticular nucleus.
AB  - The inhibitory neurons of the thalamic reticular nucleus (TRN) contribute to the
      generation of widespread oscillations in the thalamocortical system. Some TRN
      neurons are interconnected by electrical synapses, and here we tested the
      possibility that electrical synapses mediate rhythmic synchrony in juvenile rats.
      Both the incidence and strength of electrical coupling between pairs of TRN
      neurons were a steep function of intersomatic distance, and coupling was absent
      at distances >40 microm. Presynaptic spike bursts evoked much larger electrical
      postsynaptic potentials than did single presynaptic spikes. Activation of
      metabotropic glutamate receptors (mGluRs) with a bath-applied agonist or an
      endogenous ligand released during tetanic stimulation induced robust rhythms of
      the subthreshold membrane potential, with a mean frequency of approximately 10
      Hz. In the absence of fast chemical synaptic transmission, subthreshold rhythms
      and the action potentials that they evoked were well synchronized between closely
      spaced, electrically coupled pairs; rhythms in noncoupled cells were not
      synchronized. The results suggest that electrical synapses can coordinate spindle
      frequency rhythms among small clusters of mGluR-activated TRN cells.

PMID- 14724233
TI  - Differential calcium-dependent modulation of NMDA currents in CA1 and CA3
      hippocampal pyramidal cells.
AB  - Neuronal Ca2+ influx via NMDA receptors (NMDARs) is essential for the development
      and plasticity of synapses but also triggers excitotoxic cell death when critical
      intracellular levels are exceeded. Therefore, finely equilibrated mechanisms are
      necessary to ensure that NMDAR function is maintained within a homeostatic range.
      Here we describe a pronounced difference in the modulation of NMDA currents in
      two closely related hippocampal cell types, the CA1 and the CA3 pyramidal cells
      (PCs). Manipulations that increase intracellular Ca2+ levels strongly depressed
      NMDA currents in CA3 with only minor effects in CA1 PCs. Furthermore, activation
      of G(q)-coupled metabotropic receptors potentiated NMDA currents in CA1 PCs but
      depressed them in CA3 PCs. Interestingly, the CA3 type modulation of NMDARs could
      be converted into CA1-like behavior, and vice versa, by increasing Ca2+ buffering
      in CA3 cells or decreasing Ca2+ buffering in CA1 cells, respectively. Our data
      suggest that a differential Ca2+ sensitivity of the regulatory cascades targeting
      NMDARs plays a key role in determining the direction and magnitude of NMDA
      responses in various types of neurons. These findings may have important
      implications for NMDA receptor-dependent synaptic plasticity and the differential
      sensitivity of CA1 and CA3 PCs to NMDAR-dependent ischemic cell death.

PMID- 14724234
TI  - Odorant receptor expression patterns are restored in lesion-recovered rat
      olfactory epithelium.
AB  - Lesions of the olfactory periphery provide a means for examining the
      reconstitution of a diverse and highly regulated population of sensory neurons
      and the growth, en masse, of nascent axons to the bulb. The olfactory epithelium
      and its projection onto the bulb are reconstituted after ablation by methyl
      bromide gas, and some measure of olfactory function is restored. The extent to
      which the system regenerates the full repertoire of odorant receptor-expressing
      neurons, particularly their spatially restricted distribution across the
      epithelial sheet, is unknown, however, and altered odorant receptor expression
      might contribute to the persistent distortion of odorant quality that is observed
      in the lesioned-recovered animals. To address the question of receptor expression
      in the recovered epithelium, we performed in situ hybridization with digoxigenin
      labeled riboprobes for eight odorant receptors on the olfactory epithelium from
      unilaterally methyl bromide-lesioned and control rats. The data demonstrate that
      the distribution of sensory neuron types, as identified and defined by odorant
      receptor expression, is restored to normal or nearly so by 3 months after lesion.
      Likewise, the numbers of probe-labeled neurons in the lesioned-recovered
      epithelium are nearly equivalent to the unlesioned side at this time. Finally,
      our evidence suggests that odorant receptors are distributed in multiple
      overlapping bands in the normal, unlesioned, and lesioned-recovered epithelium
      rather than in the conventionally accepted three or four zones. Thus, the primary
      sensory elements required for functional recovery of the olfactory system after
      damage are restored, and altered function implies the persistence of a more
      central failure in regeneration.

PMID- 14724235
TI  - Locking the dimeric GABA(B) G-protein-coupled receptor in its active state.
AB  - G-protein-coupled receptors (GPCRs) play a major role in cell-cell communication
      in the CNS. These proteins oscillate between various inactive and active
      conformations, the latter being stabilized by agonists. Although mutations can
      lead to constitutive activity, most of these destabilize inactive conformations,
      and none lock the receptor in an active state. Moreover, GPCRs are known to form
      dimers, but the role of each protomer in the activation process remains unclear.
      Here, we show that the heterodimeric GPCR for the main inhibitory
      neurotransmitter, the GABA(B) receptor, can be locked in its active state by
      introducing two cysteines expected to form a disulphide bridge to maintain the
      binding domain of the GABA(B1) subunit in a closed form. This constitutively
      active receptor cannot be inhibited by antagonists, but its normal functioning,
      activation by agonists, and inhibition by antagonists can be restored after
      reduction with dithiothreitol. These data show that the closed state of the
      binding domain of GABA(B1) is sufficient to turn ON this heterodimeric receptor
      and illustrate for the first time that a GPCR can be locked in an active
      conformation.

PMID- 14724236
TI  - PSD93 regulates synaptic stability at neuronal cholinergic synapses.
AB  - Neuronal cholinergic synapses play important roles in both the PNS and CNS.
      However, the mechanisms that regulate the formation, maturation, and stability of
      neuronal cholinergic synapses are poorly understood. In this study, we use the
      readily accessible mouse superior cervical ganglion (SCG) and submandibular
      ganglion (SMG) to examine the assembly of the postsynaptic complex of neuronal
      cholinergic synapses. We find that novel splicing forms of PSD93 (postsynaptic
      density 93) are expressed in SCG. By immunostaining, we show that PSD93 proteins
      precisely colocalize with neuronal nicotinic acetylcholine receptors (nAChRs) at
      synapses of the SCG and SMG. Subcellular fractionation demonstrates that PSD93 is
      enriched in the PSD fraction of SCG, and coimmunoprecipitation shows that PSD93
      and neuronal nAChRs form a complex in vivo. Furthermore, two additional
      components of the well characterized glutamatergic postsynaptic complex,
      GKAP/SAPAP (guanylate kinase domain-associated protein/synapse-associated protein
      associated protein) and Shank/ProSAP family proteins, are also present at
      neuronal cholinergic synapses. To assess the function of this protein complex at
      neuronal cholinergic synapses in vivo, we examined ganglia in mice that lack
      PSD93. We find that neuronal cholinergic synapses form properly in PSD93 null
      mice. After denervation, however, synaptic clusters of nAChRs disassemble much
      faster in mice lacking PSD93 than those in wild-type mice. These results
      demonstrate that PSD93 is a key component of the postsynaptic scaffold at
      neuronal cholinergic synapses and plays an important role in synaptic stability.
      In addition, these results suggest that the mechanism of postsynaptic scaffolding
      is conserved between neuronal cholinergic and glutamatergic synapses.

PMID- 14724237
TI  - Learning modulation of odor-induced oscillatory responses in the rat olfactory
      bulb: a correlate of odor recognition?
AB  - In the first relay of information processing, the olfactory bulb (OB), odors are
      known to generate specific spatial patterns of activity. Recently, in freely
      behaving rats, we demonstrated that learning modulated oscillatory activity in
      local field potential (LFP), in response to odors, in both beta (15-40 Hz) and
      gamma (60-90 Hz) bands. The present study further characterized this odor-induced
      oscillatory activity with emphasis on its spatiotemporal distribution over the
      olfactory bulb and on its relationship with improvement of behavioral
      performances along training. For that purpose, LFPs were simultaneously recorded
      from four locations in the OB in freely moving rats performing an olfactory
      discrimination task. Electrodes were chronically implanted near relay neurons in
      the mitral cell body layer. Time-frequency methods were used to extract signal
      characteristics (amplitude, frequency, and time course) in the two frequency
      bands. Before training, odor presentation produced, on each site, a power
      decrease in gamma oscillations and a weak but significant increase in power of
      beta oscillations (approximately 25 Hz). When the training was achieved, these
      two phenomena were amplified. Interestingly, the beta oscillatory response showed
      several significant differences between the anterodorsal and posteroventral
      regions of the OB. In addition, clear-cut beta responses occurred in the signal
      as soon as animals began to master the task. As a whole, our results point to the
      possible functional importance of beta oscillatory activity in the mammalian OB,
      particularly in the context of olfactory learning.

PMID- 14724238
TI  - Serotonin enhances the resistance reflex of the locomotor network of the crayfish
      through multiple modulatory effects that act cooperatively.
AB  - Serotonin (5HT) is an endogenous amine that modifies posture in crustacea. Here,
      we examined the mechanisms of action of 5HT on the resistance reflex in crayfish
      legs. This reflex, which counteracts movements imposed on a limb, is based on a
      negative feedback system formed by proprioceptors that sense joint angle
      movements and activate opposing motoneurons. We performed intracellular
      recordings from depressor motoneurons while repetitively stretching and releasing
      a leg joint proprioceptor in a resting in vitro preparation (i.e., a preparation
      that lacks spontaneous rhythmic activity). 5HT increased the amplitude of the
      depolarization during the release phase of the proprioceptor (corresponding to an
      upward movement of the leg) and the discharge frequency of the motoneurons. The
      5HT-induced increase in the resistance reflex is caused, to a large extent, by
      polysynaptic pathways because it was very attenuated in the presence of high
      divalent cation solution. In addition to this activation of the polysynaptic
      pathways, 5HT also has postsynaptic effects that enhance the resistance reflex.
      5HT causes a tonic depolarization, as well as an increase in the time constant
      and input resistance of motoneurons. We developed a simple mathematical model to
      describe the integrative properties of the motoneurons. The conclusion of this
      study is that the input frequency and the decay time constant of the EPSPs
      interact in such a way that small simultaneous changes in these parameters can
      cause a large effect on summation. Therefore, the conjunction of presynaptic and
      postsynaptic changes produces a strong cooperative effect on the resistance
      reflex response.

PMID- 14724239
TI  - Attenuated response to stress and novelty and hypersensitivity to seizures in 5
      HT4 receptor knock-out mice.
AB  - To study the functions of 5-HT4 receptors, a null mutation was engineered in the
      corresponding gene. 5-HT4 receptor knock-out mice displayed normal feeding and
      motor behaviors in baseline conditions but abnormal feeding and locomotor
      behavior in response to stress and novelty. Specifically, stress-induced
      hypophagia and novelty-induced exploratory activity were attenuated in the knock
      out mice. In addition, pentylenetetrazol-induced convulsive responses were
      enhanced in the knock-out mice, suggesting an increase in neuronal network
      excitability. These results provide the first example of a genetic deficit that
      disrupts the ability of stress to reduce feeding and body weight and suggest that
      5-HT4 receptors may be involved in stress-induced anorexia and seizure
      susceptibility.

PMID- 14724240
TI  - Competition between phasic and asynchronous release for recovered synaptic
      vesicles at developing hippocampal autaptic synapses.
AB  - Developing hippocampal neurons in microisland culture undergo rapid and extensive
      transmitter release-dependent depression of evoked (phasic) excitatory synaptic
      activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic
      release was attenuated by repeated stimuli, asynchronous (miniature like) release
      continued at a high rate equivalent to approximately 2.8 readily releasable pools
      (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate
      release of quanta because it was resistant to sucrose-induced depletion of the
      RRP. Asynchronous and phasic release appeared to compete for a common limited
      supply of release-ready quanta because agents that block asynchronous release,
      such as EGTA-AM, led to enhanced steady-state phasic release, whereas
      prolongation of the asynchronous release time course by LiCl delayed recovery of
      phasic release from depression. Modeling suggested that the resistance of
      asynchronous release to depression was associated with its ability to out-compete
      phasic release for recovered quanta attributable to its relatively low release
      rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca2+
      concentration ([Ca2+]i) that could function over prolonged intervals between
      successive stimuli. Although phasic release was associated with a considerably
      higher peak rate of release (0.4/msec per vesicle), the [Ca2+]i microdomains that
      trigger it are brief (1 msec), and with asynchronous release present, relatively
      few quanta can accumulate within the RRP to be available for phasic release. We
      conclude that despite depression of phasic release during train stimulation,
      transmission can be maintained at a near-maximal rate by switching to an
      asynchronous mode that takes advantage of a bulk presynaptic [Ca2+]i.

PMID- 14724241
TI  - Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the
      cerebellar cortex of alert mice.
AB  - Oscillations in neuronal populations may either be imposed by intrinsically
      oscillating pacemakers neurons or emerge from specific attributes of a
      distributed network of connected neurons. Calretinin and calbindin are two
      calcium-binding proteins involved in the shaping of intraneuronal Ca2+ fluxes.
      However, although their physiological function has been studied extensively at
      the level of a single neuron, little is known about their role at the network
      level. Here we found that null mutations of genes encoding calretinin or
      calbindin induce 160 Hz local field potential oscillations in the cerebellar
      cortex of alert mice. These oscillations reached maximum amplitude just beneath
      the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient
      in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked
      to the oscillations and synchronized along the parallel fiber axis. The
      oscillations reversibly disappeared when gap junctions or either GABA(A) or NMDA
      receptors were blocked. Cutaneous stimulation of the whisker region transiently
      suppressed the oscillations. However, the intrinsic somatic excitability of
      Purkinje cells recorded in slice preparation was not significantly altered in
      mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges
      from a network mechanism combining synchronization of Purkinje cell assemblies
      through parallel fiber excitation and the network of coupled interneurons of the
      molecular layer. These findings demonstrate that subtle genetically induced
      modifications of Ca2+ homeostasis in specific neuron types can alter the observed
      dynamics of the global network.

PMID- 14724242
TI  - Improvement and decline in tactile discrimination behavior after cortical
      plasticity induced by passive tactile coactivation.
AB  - Perceptual learning can be induced by passive tactile coactivation without
      attention or reinforcement. We used functional MRI (fMRI) and psychophysics to
      investigate in detail the specificity of this type of learning for different
      tactile discrimination tasks and the underlying cortical reorganization. We found
      that a few hours of Hebbian coactivation evoked a significant increase of primary
      (SI) and secondary (SII) somatosensory cortical areas representing the stimulated
      body parts. The amount of plastic changes was strongly correlated with
      improvement in spatial discrimination performance. However, in the same subjects,
      frequency discrimination was impaired after coactivation, indicating that even
      maladaptive processes can be induced by intense passive sensory stimulation.

PMID- 14724243
TI  - Dynamic analysis of learning in behavioral experiments.
AB  - Understanding how an animal's ability to learn relates to neural activity or is
      altered by lesions, different attentional states, pharmacological interventions,
      or genetic manipulations are central questions in neuroscience. Although learning
      is a dynamic process, current analyses do not use dynamic estimation methods,
      require many trials across many animals to establish the occurrence of learning,
      and provide no consensus as how best to identify when learning has occurred. We
      develop a state-space model paradigm to characterize learning as the probability
      of a correct response as a function of trial number (learning curve). We compute
      the learning curve and its confidence intervals using a state-space smoothing
      algorithm and define the learning trial as the first trial on which there is
      reasonable certainty (>0.95) that a subject performs better than chance for the
      balance of the experiment. For a range of simulated learning experiments, the
      smoothing algorithm estimated learning curves with smaller mean integrated
      squared error and identified the learning trials with greater reliability than
      commonly used methods. The smoothing algorithm tracked easily the rapid learning
      of a monkey during a single session of an association learning experiment and
      identified learning 2 to 4 d earlier than accepted criteria for a rat in a 47 d
      procedural learning experiment. Our state-space paradigm estimates learning
      curves for single animals, gives a precise definition of learning, and suggests a
      coherent statistical framework for the design and analysis of learning
      experiments that could reduce the number of animals and trials per animal that
      these studies require.

PMID- 14724244
TI  - Keratan sulfate proteoglycan phosphacan regulates mossy fiber outgrowth and
      regeneration.
AB  - We have examined the role of chondroitin sulfate proteoglycans (CSPGs) and
      keratan sulfate proteoglycans (KSPGs) in directing mossy fiber (MF) outgrowth and
      regeneration in rat hippocampal slice cultures. MFs normally exhibit a very
      specific innervation pattern that is restricted to the stratum lucidum (SL). In
      addition, MFs in hippocampal slice cultures will regenerate this specific
      innervation pattern after transection. CSPGs are one of the best characterized
      inhibitory axon guidance molecules in the CNS and are widely expressed in all
      areas of the hippocampus except SL. KSPGs are also widely expressed in the
      hippocampus, but their role in axon outgrowth has not been extensively studied in
      the CNS where phosphacan is the only protein that appears to contain KS-GAGs.
      Cultured hippocampal slices were treated with either chondroitin ABC lyase or
      keratanases to reduce the inhibitory axon guidance properties of CS and KS
      proteoglycans, respectively. The ability of transected MFs to regenerate their
      normal innervation pattern after digestion of CS and KS-GAGS sugars with these
      enzymes was examined. Only keratanase treatment resulted in misrouting of MFs.
      Identifying the mechanism by which keratanase produced MF misrouting is
      complicated by the presence of splice variants of the phosphacan gene that
      include the extracellular form of phosphacan and the transmembrane receptor
      protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta). Both forms of phosphacan
      are made by astrocytes, suggesting that keratanase alters MF outgrowth by
      modifying astrocyte function.

PMID- 14724245
TI  - Immunoblockage of 9-O-acetyl GD3 ganglioside arrests the in vivo migration of
      cerebellar granule neurons.
AB  - During development of the cerebellum, radial glial cells guide the migration of
      granule cell precursors from the external granular cell layer toward the internal
      granular cell layer. The cellular membranes of migrating neurons and glial fibers
      organize a specialized migration junction at the site of contact between these
      cells, and several molecules have been implicated in the control of this glial
      guided neuronal migration program. The monoclonal antibody Jones (mAb Jones)
      recognizes the ganglioside 9-O-acetyl GD3, which is expressed in migratory
      profiles in the developing and adult CNS. Recently, this ganglioside was
      suggested to play a role in neuronal migration in cerebellar cultures. In this
      report, we use antibody perturbation assays to investigate a possible role of 9-O
      acetyl GD3 in the neuronal migration program in vivo. The results show that
      chronic intracerebroventricular administration of mAb Jones arrests neuronal
      migration in the developing cerebellum of live animals. Proliferating granule
      cell precursors were labeled with 5-bromo-2'-deoxyuridine (BrdU), and their
      migratory behavior was analyzed and compared with control groups. Immunoblockage
      of 9-O-acetyl GD3 arrests 43% of the BrdU-labeled granule precursors in the
      external granular cell layer. Together with our previous results, this report
      strongly suggests that the ganglioside 9-O-acetyl GD3 plays a crucial role in the
      migration of cerebellar granule cells along radial glial fibers in the developing
      rat cerebellum.

PMID- 14724246
TI  - 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory
      response in glial cells: a possible role of AMP-activated protein kinase.
AB  - AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP
      ratio and plays a central role in the regulation of energy homeostasis and
      metabolic stress. A pharmacological activator of AMPK, 5-amino-4-imidazole
      carboxamide riboside (AICAR) inhibited lipopolysaccharide (LPS)-induced
      expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin
      1beta, and interleukin-6) and inducible nitric oxide synthase in primary rat
      astrocytes, microglia, and peritoneal macrophages. AICAR attenuates the LPS
      induced activation of nuclear factor kappaB via downregulation of IkappaB kinase
      alpha/beta activity. It also inhibits nuclear translocation of CCAAT/enhancer
      binding protein (C/EBP) transcription factor by inhibiting the expression of
      C/EBP-delta in brain glial cells. The dominant negative form of AMPKalpha2
      (D157A) and its antisense documents a possible role of AMPK in the regulation of
      the cellular proinflammatory process. AICAR also inhibited the production of
      inflammatory mediators in serum and their expression in CNS of rats injected with
      a sublethal dose of LPS by intraperitoneal injection. These observations in
      cultured cells as well as in the animal model suggest that AICAR may be of
      therapeutic value in treating inflammatory diseases.

PMID- 14724247
TI  - Long-term potentiation in an avian basal ganglia nucleus essential for vocal
      learning.
AB  - Vocal learning in songbirds provides an excellent model for sensorimotor learning
      in vertebrates, with an accessible, well-defined behavior and discrete neural
      substrate. The rich behavioral plasticity exhibited by songbirds, however,
      contrasts starkly with the scarcity of candidate cellular mechanisms. Here, we
      report for the first time on an activity-dependent form of synaptic plasticity in
      area X, a component of the song system required for song learning and song
      maintenance. In slice preparations of zebra finch area X, pairing of high
      frequency presynaptic stimulation with postsynaptic depolarization induces
      Hebbian long-term potentiation (LTP) of the glutamatergic inputs to spiny
      neurons. This form of LTP requires activation of NMDA receptors and D1-like
      dopamine receptors. In addition, LTP is observed in birds as young as 47 d after
      hatching and also in adult birds but not in younger birds, providing evidence of
      developmental regulation of the onset of synaptic plasticity. These properties
      make this form of LTP the best known candidate mechanism for reinforcement-based
      vocal learning in juveniles and song maintenance in adult birds.

PMID- 14724248
TI  - Androgens increase spine synapse density in the CA1 hippocampal subfield of
      ovariectomized female rats.
AB  - The effects of androgen on the density of spine synapses on pyramidal neurons in
      the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female
      rats. Treatment of OVX rats with testosterone propionate (TP; 500 microg/d, s.c.,
      2 d) significantly increased spine synapse density (from 0.661 +/- 0.016 spine
      synapse/microm3 in OVX rats to 1.081 +/- 0.018 spine synapse/microm3 after TP
      treatment). A smaller, but still statistically significant, increase in synapse
      density (0.955 +/- 0.029 spine synapse/microm3) was observed in OVX animals after
      treatment with the nonaromatizable androgen dihydrotestosterone (DHT; 500
      microg/d, s.c., 2 d). Administration of 1 mg of letrozole, a powerful
      nonsteroidal aromatase inhibitor, 1 hr before the steroid injections almost
      completely blocked the synaptic response to testosterone, resulting in a mean
      synapse density (0.723 +/- 0.003 spine synapse/microm3) only slightly higher than
      in OVX control rats. By contrast, the response to DHT was unaffected by letrozole
      pretreatment. These data suggest that androgen secretion during the female
      reproductive cycle may contribute to cyclical changes in hippocampal synaptic
      density. They also indicate that androgen treatment may be as effective as
      estrogen replacement in reversing the decline in hippocampal CA1 spine synapses
      that follows loss of ovarian function. Induction of hippocampal synapse formation
      by androgen is not mediated entirely via intracerebral estrogen biosynthesis,
      however, because aromatase-independent mechanisms also significantly affect CA1
      spine synapse density.

PMID- 14724249
TI  - Limited role of developmental programmed cell death pathways in Drosophila norpA
      retinal degeneration.
AB  - We examined the role of programmed cell death (PCD) pathways in retinal
      degeneration caused by a mutation in the norpA gene. norpA degeneration shows
      morphological hallmarks of programmed cell death, specifically cytoplasmic
      condensation and engulfment of the dying photoreceptor cells by neighboring
      retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors
      lacking rpr, hid, and grim show that these PCD inducers are not required for
      norpA degeneration. We showed previously that ectopic expression of either rpr or
      hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed
      by the coexpression of the baculoviral P35 caspase inhibitor. In contrast,
      expression of P35 does not suppress norpA retinal degeneration, although a small
      delay in the rate of degeneration is observed in low light-low temperature
      conditions. P35 does not alter the morphological characteristics of norpA cell
      death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a
      dominant-negative form of the Dronc caspase, even when coexpressed with P35, does
      not dramatically alter the time course of norpA degeneration. These results
      establish that the pathways responsible for PCD in development do not play a
      major role in adult retinal degeneration caused by norpA.

PMID- 14724250
TI  - Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an
      Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals
      and altered membrane excitability.
AB  - Disruptions in intracellular Ca2+ signaling are proposed to underlie the
      pathophysiology of Alzheimer's disease (AD), and it has recently been shown that
      AD-linked mutations in the presenilin 1 gene (PS1) enhance inositol triphosphate
      (IP3)-mediated Ca2+ liberation in nonexcitable cells. However, little is known of
      these actions in neurons, which are the principal locus of AD pathology. We
      therefore sought to determine how PS1 mutations affect Ca2+ signals and their
      subsequent downstream effector functions in cortical neurons. Using whole-cell
      patch-clamp recording, flash photolysis, and two-photon imaging in brain slices
      from 4-5-week-old mice, we show that IP3-evoked Ca2+ responses are more than
      threefold greater in PS1(M146V) knock-in mice relative to age-matched
      nontransgenic controls. Electrical excitability is thereby reduced via enhanced
      Ca2+ activation of K+ conductances. Action potential-evoked Ca2+ signals were
      unchanged, indicating that PS1(M146V) mutations specifically disrupt
      intracellular Ca2+ liberation rather than reduce cytosolic Ca2+ buffering or
      clearance. Moreover, IP3 receptor levels are not different in cortical
      homogenates, further suggesting that the exaggerated cytosolic Ca2+ signals may
      result from increased store filling and not from increased flux through
      additional IP3-gated channels. Even in young animals, PS1 mutations have profound
      effects on neuronal Ca2+ and electrical signaling: cumulatively, these
      disruptions may contribute to the long-term pathophysiology of AD.

PMID- 14724251
TI  - The central fragment of Reelin, generated by proteolytic processing in vivo, is
      critical to its function during cortical plate development.
AB  - Reelin is a large extracellular protein that controls cortical development. It
      binds to lipoprotein receptors very-low-density lipoprotein receptor and
      apolipoprotein-E receptor type 2, thereby inducing phosphorylation of the adapter
      Dab1. In vivo, Reelin is cleaved into three fragments, but their respective
      function is unknown. Here we show the following: (1) the central fragment is
      necessary and sufficient for receptor binding in vitro and for Dab1
      phosphorylation in neuronal cultures; (2) Reelin does not bind the protocadherin
      cadherin-related neuronal receptor (CNR1) as reported previously; (3) Reelin and
      its central fragment are equally able to rescue the reeler phenotype in a slice
      culture assay; and (4) anti-receptor antibodies can induce Dab1 phosphorylation
      but do not correct the reeler phenotype in slices. These observations show that
      the function of Reelin is critically dependent on the central fragment generated
      by processing but primarily independent of interactions with CNR1 and on the N
      terminal region. They also indicate that events acting in parallel to Dab1
      phosphorylation might be required for full activity.

PMID- 14724252
TI  - Brain-derived neurotrophic factor modulates fast synaptic inhibition by
      regulating GABA(A) receptor phosphorylation, activity, and cell-surface
      stability.
AB  - The efficacy of GABAergic synaptic inhibition is a principal factor in
      controlling neuronal activity. We demonstrate here that brain-derived
      neurotrophic factor modulates the activity of GABA(A) receptors, the main sites
      of fast synaptic inhibition in the brain, within minutes of application.
      Temporally, this comprised an early enhancement in the miniature IPSC amplitude,
      followed by a prolonged depression. This modulation was concurrent with enhanced
      PKC-mediated phosphorylation, followed by protein phosphatase 2A (PP2A)-mediated
      dephosphorylation of the GABA(A) receptor. Mechanistically, these events were
      facilitated by differential recruitment of PKC, receptor for activated C-kinase,
      and PP2A to GABA(A) receptors, depending on the phosphorylation state of the
      receptor beta3-subunit. Thus, transient formation of GABA(A) receptor signaling
      complexes has the potential to provide a basis for acute changes in receptor
      function underlying GABAergic synaptic plasticity.

PMID- 14724253
TI  - Discrimination of voiced stop consonants based on auditory nerve discharges.
AB  - Previous studies of the neural representation of speech assumed some form of
      neural code, usually discharge rate or phase locking, for the representation. In
      the present study, responses to five synthesized CVC_CV (e.g., /dad_da/)
      utterances have been examined using information-theoretic distance measures [or
      Kullback-Leibler (KL) distance] that are independent of a priori assumptions
      about the neural code. The consonants in the stimuli fall along a continuum from
      /b/ to /d/ and include both formant-frequency (F1, F2, and F3) transitions and
      onset (release) bursts. Differences in responses to pairs of stimuli, based on
      single-fiber auditory nerve responses at 70 and 50 dB sound pressure level, have
      been quantified, based on KL and KL-like distances, to show how each portion of
      the response contributes to information coding and the fidelity of the encoding.
      Distances were large at best frequencies, in which the formants differ but were
      largest for fibers encoding the high-frequency release bursts. Distances computed
      at differing time resolutions show significant information in the temporal
      pattern of spiking, beyond that encoded by rate, at time resolutions from 1-40
      msec. Single-fiber just noticeable differences (JNDs) for F2 and F3 were computed
      from the data. These results show that F2 is coded with greater fidelity than F3,
      even among fibers tuned to F3, and that JNDs are larger in the syllable final
      consonant than in the releases.

PMID- 14724254
TI  - Suppression of p75NTR does not promote regeneration of injured spinal cord in
      mice.
AB  - The neurotrophin receptor p75NTR is the coreceptor for Nogo receptor, mediating
      growth cone collapse in vitro by MAG, myelin oligodendrocyte glycoprotein (Omgp),
      and Nogo. Whether p75NTR plays any role in the failure of nerve regeneration in
      vivo is not known. Immunohistochemical data showed that p75NTR was expressed in
      only a very small subset of ascending sensory axons but not in any corticospinal
      axons in the dorsal column of either normal or injured spinal cord. Using p75NTR
      deficient mice, we showed that the depletion of the functional p75NTR did not
      promote the regeneration of the descending corticospinal tract and ascending
      sensory neurons in the spinal cord 2 weeks after spinal cord injury. Local
      administration of p75NTR-Fc fusion molecule, the dominant-negative receptor to
      block the function of neurite outgrowth inhibitors, did not improve regeneration
      of ascending sensory neurons in the injured spinal cord. Our results suggest that
      p75NTR may not be a critical molecule mediating the function of myelin-associated
      inhibitory factors in vivo.

PMID- 14724255
TI  - Magnitude of dopamine release in medial prefrontal cortex predicts accuracy of
      memory on a delayed response task.
AB  - Modulation of neural function in the prefrontal cortex (PFC) by dopamine (DA) is
      essential for higher cognitive processes related to attention, working memory,
      and planning of future behavior. The present study demonstrates that DA efflux in
      the PFC is increased in a phasic manner when a rat engages in search behavior for
      food reward on an eight arm radial maze guided by memory, independent of whether
      or not reward is obtained for making the correct choice. Furthermore, disruption
      of accurate recall of the correct pattern of arms induced by increasing the delay
      period from 30 min to 1 or 6 hr, is associated with attenuated DA efflux during
      the retrieval phase of the task. The observed increase in DA efflux in the
      absence of reward at a 30 min delay and the minimal increase during consumption
      of the same quantity of food during poor performance after an unexpected 6 hr
      delay, argue against a simple relationship between DA function in the PFC and
      reward processes. Instead, these data demonstrate a close functional relationship
      between the release of DA from terminals within the PFC and the retrieval of
      specific trial unique memories; furthermore, the magnitude of mesocortical DA
      efflux is predictive of the accuracy of this form of memory.

PMID- 14724256
TI  - Monocular enucleation induces nuclear localization of calcium/calmodulin
      dependent protein kinase IV in cortical interneurons of adult monkey area V1.
AB  - Elevation of intracellular Ca2+ levels activates calcium/calmodulin-dependent
      protein kinase (CaMK) IV, which in turn plays an important role in
      neuroprotection and neuroplasticity. The possibility that CaMKIV is similarly
      involved in neocortical tissue has not been examined previously, especially with
      regard to the plastic nature of ocular dominance features in the primary visual
      cortex (area V1). We addressed this question by way of monocular enucleation (ME)
      to disrupt sensory input and examine CaMKIV expression changes in monkey area V1.
      Immunohistochemical staining of area V1 in normal infants showed a nuclear
      presence of CaMKIV, which did not changed after ME. However, a striking set of
      layer- and time-dependent changes in nuclear CaMKIV expression was observed in
      adult area V1 after ME. A strong increase in nuclear CaMKIV levels was evident in
      cortical layers II/III and VI after 1 d of ME and in layer IVC after 5 d of ME.
      These specific laminar changes persisted after 30 d of ME and, most notably,
      showed a columnar profile in which CaMKIV expression was linked to open-eye
      columns. Real-time quantitative reverse transcription-PCR and Western blot
      analysis showed that total amounts of CaMKIV mRNA and protein remained unchanged
      after ME, suggesting that a nuclear translocation may occur from the cytoplasm.
      Finally, double-label immunohistochemical staining with a pyramidal cell marker
      (SMI-32) showed that CaMKIV was absent in this subtype, whereas coincidental
      expression with GABA, parvalbumin, and calretinin, but not calbindin, showed its
      clear presence in a subset of interneurons. We propose that CaMKIV activity
      within diverse groups of cortical interneurons may play an important role in
      adaptive plastic reorganization of adult neocortical tissue.

PMID- 14724257
TI  - Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in
      astrocytes and death of neurons through activation of NADPH oxidase.
AB  - Beta-amyloid (betaA) peptide is strongly implicated in the neurodegeneration
      underlying Alzheimer's disease, but the mechanisms of neurotoxicity remain
      controversial. This study establishes a central role for oxidative stress by the
      activation of NADPH oxidase in astrocytes as the cause of betaA-induced neuronal
      death. betaA causes a loss of mitochondrial potential in astrocytes but not in
      neurons. The mitochondrial response consists of Ca2+-dependent transient
      depolarizations superimposed on a slow collapse of potential. The slow response
      is both prevented by antioxidants and, remarkably, reversed by provision of
      glutamate and other mitochondrial substrates to complexes I and II. These
      findings suggest that the depolarization reflects oxidative damage to metabolic
      pathways upstream of mitochondrial respiration. Inhibition of NADPH oxidase by
      diphenylene iodonium or 4-hydroxy-3-methoxy-acetophenone blocks betaA-induced
      reactive oxygen species generation, prevents the mitochondrial depolarization,
      prevents betaA-induced glutathione depletion in both neurons and astrocytes, and
      protects neurons from cell death, placing the astrocyte NADPH oxidase as a
      primary target of betaA-induced neurodegeneration.

PMID- 14724258
TI  - Control of cortical neuron migration and layering: cell and non cell-autonomous
      effects of p35.
AB  - The migration, arrest, and ultimately positioning of cortical neurons require
      signaling activity from Reelin as well as from cyclin-dependent kinase 5 (Cdk5).
      Although both molecules control neuronal positioning, they achieve their effects
      by quite separate molecular pathways. Cdk5 is a serine-threonine kinase, the
      activity of which is dependent on its activating subunits p35 and p39. Mice
      deficient in Cdk5, p35, or both p35 and p39 display the hallmarks of disturbed
      cortical development, including cortical layer inversion, neuronal
      disorientation, and abnormal fiber infiltration. To distinguish between the cell-
      and non cell-autonomous functions of p35, we constructed p35+/+ <--> p35-/-
      chimeras using the lacZ gene as an independent marker for p35+/+ cells. In this
      shared developmental space, wild-type and mutant neurons behaved cell
      autonomously with respect to layering. Wild-type cells formed a properly layered
      supercortex that is mirrored by an inverted mutant cortex lying underneath.
      However, this genotype-specific behavior was confined to the pyramidal
      population, and interneurons belonging to either genotype were indiscriminately
      distributed. However, there was also non cell-autonomous rescue of mutant
      neurons, and this rescue was specific only to early-born pyramidal neurons
      belonging to layer V. Rescued neurons reached the correct layer address and
      possessed appropriate neuronal morphology, orientation, and projections. Later
      born neurons belonging to layers II and III were not rescued. These results
      demonstrate that p35 signaling can have both cell- and non cell-autonomous
      consequences, and their effects are not uniformly shared by cortical neurons born
      at different times or born at different places (projection neurons vs
      interneurons).

PMID- 14724259
TI  - Modulation of associative human motor cortical plasticity by attention.
AB  - The role of attention in generating motor memories remains controversial
      principally because it is difficult to separate the effects of attention from
      changes in kinematics of motor performance. We attempted to disentangle attention
      from performance effects by varying attention while plasticity was induced in
      human primary motor cortex by external stimulation in the absence of voluntary
      movement. A paired associative stimulation (PAS) protocol was employed consisting
      of repetitive application of single afferent electric stimuli, delivered to the
      right median nerve, paired with single-pulse transcranial magnetic stimulation
      (TMS) over the optimal site for activation of the right abductor pollicis brevis
      muscle (APB) to generate near-synchronous events in the left primary motor
      cortex. In experiment 1, the spatial location of attention was varied. PAS failed
      to induce plasticity when the subject's attention was directed to their left
      hand, away from the right target hand the cortical representation of which was
      being stimulated by PAS. In experiment 2, the grade of attention to the target
      hand was manipulated. PAS-induced plasticity was maximal when the subject viewed
      their target hand, and its magnitude was slightly reduced when the subject could
      only feel their hand. Conversely, plasticity was completely blocked when the
      subject's attention was diverted from the target hand by a competing cognitive
      task. A similar modulation by attention was observed for PAS-induced changes in
      the duration of the silent period evoked by TMS in voluntarily contracted muscle.
      Associative plasticity in the human motor cortex depends decisively on attention.

PMID- 14724260
TI  - Milk ejection burst-like electrical activity evoked in supraoptic oxytocin
      neurons in slices from lactating rats.
AB  - To examine the mechanisms underlying milk-ejection bursts of oxytocin (OT)
      neurons during suckling, both in vivo and in vitro studies were performed on
      supraoptic OT neurons from lactating rats. The bursts were first recorded
      extracellularly in anesthetized rats. Burst-related electrical parameters were
      essentially the same as previous reports except for a trend toward transient
      decreases in basal firing rates immediately preceding the burst. From putative OT
      neurons in slices with extracellular recordings, bursts that closely mimicked the
      in vivo bursts were elicited by phenylephrine, an alpha1-adrenoceptor agonist, in
      a low-Ca(2+) medium. Moreover, in whole cell patch-clamp recordings, the in vitro
      bursts were recorded from immunocytochemically identified OT neurons. After a
      transient decrease in the basal firing rate, the in vitro bursts started with a
      sudden increase in the firing rate, quickly reaching a peak level, then gradually
      decaying, and ended with a postburst inhibition. A brief depolarization of the
      membrane potential and an increase in membrane conductance appeared after the
      onset of the burst. Spikes during a burst were characterized by a significant
      increase in the duration and decrease in the amplitude around the peak rate
      firing. These bursts were significantly different from short-lasting burst firing
      of vasopressin neurons in membrane potential changes, time to reach peak firing
      rate, spike amplitude and duration during peak rate firing. Our extensive
      analysis of these results suggests that the in vitro burst is a useful model for
      further study of mechanisms underlying milk-ejection bursts of OT neurons in
      vivo.

PMID- 14724261
TI  - Auditory responses in multiple sensorimotor song system nuclei are co-modulated
      by behavioral state.
AB  - Auditory responsiveness in nucleus HVC, a high-order sensorimotor area of the
      avian song system, is modulated by changes in behavioral state. Modulation is not
      observed in the primary thalamo-recipient auditory area Field L, the indirect
      source of auditory input to HVC. In this study, we show that auditory
      responsiveness in nucleus interfacialis (NIf), the immediate auditory afferent to
      HVC, is modulated by behavioral state. While auditory responsiveness is generally
      greater in NIf during wakefulness and in HVC during sedation, simultaneous
      recordings reveal a co-variation of auditory response magnitude. This co
      variation is observed both in awake birds, where responses are spontaneously
      variable, and in sedated birds during manipulations of arousal levels. Auditory
      responses in NIf and HVC, which are selective for the bird's own song (BOS)
      during sedation, become predominantly unselective during wakefulness. This loss
      of selectivity is accompanied by a decrease in the similarity of NIf and HVC
      response patterns. To explore the role of NIf in shaping HVC auditory responses,
      we pharmacologically manipulated NIf while recording in HVC. Injection of the
      GABA(A) agonist muscimol into NIf eliminated most spontaneous activity and all
      auditory responses in the ipsilateral HVC, while injections of the GABA(A)
      antagonist bicuculline increased HVC auditory responsiveness and selectivity.
      These findings indicate that HVC is not the initial site of behavioral state
      dependent modulation in the song system. Together with the suppression of HVC
      auditory responses by muscimol in NIf, these results suggest that NIf plays an
      important role in the flow of auditory information to HVC.

PMID- 14724262
TI  - EMG responses to an unexpected load in fast movements are delayed with an
      increase in the expected movement time.
AB  - When moving an object, the motor system estimates the dynamic properties of the
      object and then controls the movement using a combination of predictive
      feedforward control and proprioceptive feedback. In this study, we examined how
      the feedforward and proprioceptive feedback processes depend on the expected
      movement task. Subjects made fast elbow flexion movements from an initial
      position to a target. The experimental protocol included movements made over a
      short and a long distance against an expected light or heavy inertial load. In
      each task in a few randomly chosen trials, a motor applied an unexpected viscous
      load that produced a velocity error, defined as the difference between the
      expected and unexpected velocities, and electromyographic (EMG) responses. The
      EMG responses appeared not earlier than 170-250 ms from the agonist EMG onset.
      Our main finding is that the onset of the EMG responses was correlated with the
      expected time of peak velocity, which increased for longer distances and larger
      loads. An analysis of the latency of the EMG responses with respect to the
      velocity error suggested that the EMG responses were due to segmental reflexes.
      We conclude that segmental reflex gains are centrally modulated with the time
      course dependent on the expected movement task. According to this view, the
      control of fast point-to-point movement is feedforward from the agonist EMG onset
      until the expected time of peak velocity after which the segmental reflex
      feedback is briefly facilitated.

PMID- 14724263
TI  - Auditory thalamus bursts in anesthetized and non-anesthetized states:
      contribution to functional properties.
AB  - Over the last 10 years, high-frequency bursts of action potentials have been the
      subject of intense researches to understand their potential role in information
      encoding. Based on recordings from auditory thalamus neurons (n = 302) collected
      during anesthesia (pentobarbital, urethan, or ketamine/xylazine), waking (W), and
      slow-wave sleep (SWS), we investigated how bursts participate to frequency
      tuning, intensity-function, response latency (and latency variability), and
      stimulus detectability. Although present in all experimental conditions, bursts
      never dominated the cells mode of discharge: the highest proportion was found
      during ketamine/xylazine anesthesia (22%), the lowest during waking (4.5%). In
      all experimental conditions, bursts preferentially occurred at or around the
      cells best frequency (BF), thus increasing the frequency selectivity. This effect
      was observed at both the intensities producing the highest and the lowest evoked
      responses. Testing the intensity-functions indicated that for most of the cells,
      there was no systematic relationship between burst proportion and responses
      strength. Under several conditions (W, SWS, and urethan), when cells exhibited
      bursts >20%, the variability of their response latency was reduced in burst mode
      compared with single-spike mode. During W, this effect was accompanied by a
      reduction of the response latency. Finally, a receiver operating characteristic
      analysis indicated no particular relation between bursts and stimulus
      detectability. Compared with single-spike mode, which is present for broader
      frequency ranges, the prominence of bursts at the BF should contribute to filter
      information reaching the targets of medial geniculate cells at both cortical and
      subcortical levels.

PMID- 14724264
TI  - Eye movements of the murine P/Q calcium channel mutant rocker, and the impact of
      aging.
AB  - Mutations in the gene encoding the ion pore of the P/Q voltage-activated calcium
      channel (CACNA1A) are predicted to alter synaptic transmission and dendritic
      excitability within cerebellar granule and Purkinje cells. Determining the
      relationships between these alterations, neuronal activity, and behavior may
      yield insight into the relationship between neuronal intrinsic properties and
      signal processing within the ocular motor system. Toward this end, we compared
      ocular motor performance in the CACNA1A mutant rocker and C57BL/6 controls.
      Average vertical eye position was abnormally elevated in the mutants, a finding
      that may be analogous to downbeat nystagmus seen in human cerebellar disorders.
      Fast phases of vestibular nystagmus were slowed by approximately 18% of control
      values. The angular vestibuloocular reflex (VOR) in darkness and light (visual
      VOR, or VVOR), assessed at 0.1-1.6 Hz, exhibited subnormal gains at the highest
      stimulus frequencies and increased phase leads at the lowest stimulus
      frequencies. Horizontal optokinetic responses to constant velocity drum rotation
      of +/-2.5-40 degrees/s exhibited minimally reduced gains. Attempts to increase
      VOR gain by concomitant optokinetic and vestibular stimulation were confounded by
      the tendency of the mice to habituate to repetitive vestibular stimulation, but
      attempts to induce coupling of vertical eye movements to horizontal vestibular
      stimulation (cross-axis adaptation) generated rapid plastic changes in controls
      and little effect in mutants. With the notable exceptions of the vertical
      elevation and optokinetic gains, the ocular motor abnormalities were stable over
      a broad range of animal age, a result compatible with the abnormalities arising
      as direct consequences of the inborn alteration in calcium channel biophysics.

PMID- 14724265
TI  - Multiple spontaneous rhythmic activity patterns generated by the embryonic mouse
      spinal cord occur within a specific developmental time window.
AB  - Spontaneous rhythmic activity is a ubiquitous phenomenon in developing neural
      networks and is assumed to play an important role in the elaboration of mature
      circuitry. Here we describe the day-by-day evolution of spontaneous activity in
      the embryonic mouse spinal cord and show that, at a specific developmental stage,
      2 distinct rhythms coexist. On embryonic days E12.5 and E13.5, we observed a
      single type of regularly recurring short spike-episodes synchronized across
      cervical, thoracic, and lumbar levels. By E14.5, in addition to this motor
      rhythm, another type of spontaneous synchronous activity appeared, characterized
      by much longer lasting episodes separated by longer time intervals. On E15.5,
      these long episodes disappeared. Short episodes were less numerous and more
      irregular except at the cervical level where a rhythm was occasionally observed.
      By E16.5, this cervical rhythm became more robust, whereas the lumbar level fell
      almost silent. Surprisingly, at E17.5, spontaneous activity resumed at caudal
      levels, now characterized by numerous erratic short episodes. A striking
      ontogenetic feature of spontaneous activity was the occurrence of long episodes
      only at E14.5. Although concomitant at all levels of the spinal cord, long
      episodes displayed different patterns along the spinal cord, with tonic firing at
      the thoracic level and rhythmic discharge with occasional sequences of left/right
      alternation at the lumbar level. Thus at E14.5, the originally synchronized
      network has started to segregate into more specialized subnetworks. In
      conclusion, this work suggests that ongoing spontaneous rhythms do not follow a
      smooth evolution during maturation, but rather undergo profound changes at very
      specific stages.

PMID- 14724266
TI  - Distribution of motor unit force in human extensor digitorum assessed by spike
      triggered averaging and intraneural microstimulation.
AB  - A peculiar aspect of the muscular organization of the human hand is that the main
      flexors and extensors of the fingers are muscles that each give rise to four
      parallel tendons that insert on all the fingers. It has been hypothesized that
      these multi-tendoned muscles are comprised of functional compartments, with each
      finger controlled by a discrete population of motor units. The purpose of this
      study was to determine the force distribution across the four fingers for motor
      units in human extensor digitorum (ED), a multi-tendoned muscle that extends the
      fingers. The force distribution was assessed by spike-triggered averaging and
      intraneural microstimulation for 233 and 18 ED units, respectively. A selectivity
      index from 0 (force equally distributed across the fingers) to 1.0 (force
      concentrated on a single finger) was used to quantify the distribution of motor
      unit force across the four digits. The mean selectivity index was high for ED
      motor units assessed with intraneural microstimulation (0.90 +/- 0.28) and was
      significantly greater than that obtained with spike-triggered averaging (0.38 +/-
      0.14). Therefore it is likely that each finger is acted on by ED through a
      discrete population of motor units and that weak synchrony between motor units in
      different compartments of ED may have contributed to the appearance of spike
      triggered average force on multiple fingers. Moreover, the high selectivity of
      motor units for individual fingers may provide the mechanical substrate needed
      for highly fractionated movements of the human hand.

PMID- 14724267
TI  - Variations in motor patterns during fictive rostral scratching in the turtle:
      knee-related deletions.
AB  - Agonist motor neurons usually alternate between activity and quiescence during
      normal rhythmic behavior; antagonist motor neurons are usually active during
      agonist motor neuron quiescence. During an antagonist deletion, a naturally
      occurring motor-pattern variation, there is no antagonist activity and no
      quiescence between successive bursts of agonist activity. Motor neuron recordings
      of normal fictive rostral scratching in the turtle displayed rhythmic alternation
      between activity and quiescence for hip flexors, knee flexors, and knee
      extensors. Knee-flexor activity occurred during knee-extensor quiescence. During
      a hip-extensor deletion, a variation of rostral scratching, rhythmic hip-flexor
      bursts occurred without intervening hip-flexor quiescence. There were 3 distinct
      patterns of knee motor activity during the cycle before or after a hip-extensor
      deletion. In most cycles, there was knee flexor-extensor rhythmic alternation. In
      some cycles, termed knee-flexor deletions, there was no knee-flexor activity and
      rhythmic knee-extensor bursts occurred without intervening knee-extensor
      quiescence. In other cycles, termed knee-extensor deletions, there was no knee
      extensor activity and rhythmic knee-flexor bursts occurred without intervening
      knee-flexor quiescence. The concept of a module refers to a population of motor
      neurons and interneurons with similar activity patterns; interneurons in a module
      coordinate agonist and antagonist motor neuron activities, either with excitation
      of agonist motor neurons and interneurons, or with inhibition of antagonist motor
      neurons and interneurons. Previous studies of hip-extensor deletions support the
      concept of a rhythmogenic hip-flexor module. The knee-related deletions described
      here support the concept of rhythmogenic knee-flexor and knee-extensor modules
      linked by reciprocal inhibition.

PMID- 14724268
TI  - The discovery of unconventional myosins: serendipity or luck?

PMID- 14724269
TI  - Localization of the serine protease-binding sites in the collagen-like domain of
      mannose-binding protein: indirect effects of naturally occurring mutations on
      protease binding and activation.
AB  - Mutations in the collagen-like domain of serum mannose-binding protein (MBP)
      interfere with the ability of the protein to initiate complement fixation through
      the MBP-associated serine proteases (MASPs). The resulting deficiency in the
      innate immune response leads to susceptibility to infections. Studies have been
      undertaken to define the region of MBP that interacts with MASPs and to determine
      how the naturally occurring mutations affect this interaction. Truncated and
      modified MBPs and synthetic peptides that represent segments of the collagen-like
      domain of MBP have been used to demonstrate that MASPs bind on the C-terminal
      side of the hinge region formed by an interruption in the Gly-X-Y repeat pattern
      of the collagen-like domain. The binding sites for MASP-2 and for MASP-1 and -3
      overlap but are not identical. The two most common naturally occurring mutations
      in MBP result in substitution of acidic amino acids for glycine residues in Gly-X
      Y triplets on the N-terminal side of the hinge. Circular dichroism analysis and
      differential scanning calorimetry demonstrate that the triple helical structure
      of the collagen-like domain is largely intact in the mutant proteins, but it is
      more easily unfolded than in wild-type MBP. Thus, the effect of the mutations is
      to destabilize the collagen-like domain, indirectly disrupting the binding sites
      for MASPs. In addition, at least one of the mutations has a further effect on the
      ability of MBP to activate MASPs.

PMID- 14724270
TI  - Identification of a new glycerol-3-phosphate acyltransferase isoenzyme, mtGPAT2,
      in mitochondria.
AB  - Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial and rate
      limiting step of glycerolipid synthesis. Two distinct GPAT isoenzymes had been
      identified in mammalian tissues, an N-ethylmaleimide (NEM)-sensitive isoform in
      the endoplasmic reticulum membrane (microsomal GPAT) and an NEM-resistant form in
      the outer mitochondrial membrane (mtGPAT). Although only mtGPAT has been cloned,
      the microsomal and mitochondrial GPAT isoforms can be distinguished, because they
      differ in acyl-CoA substrate preference, sensitivity to inhibition by
      dihydroxyacetone phosphate and polymixin B, temperature sensitivity, and ability
      to be activated by acetone. The preponderance of evidence supports a role for
      mtGPAT in synthesizing the precursors for triacylglycerol synthesis. In mtGPAT(-/
      ) mice, PCR genotyping and Northern analysis showed successful knockout of
      mtGPAT; however, we detected a novel NEM-sensitive GPAT activity in mitochondrial
      fractions and an anti-mtGPAT immunoreactive protein in liver mitochondria, but
      not in microsomes. Rigorous analysis using two-dimensional gel electrophoresis
      revealed that the anti-mtGPAT immunoreactive proteins in wild type and mtGPAT(-/
      ) liver mitochondria have different isoelectric points. These results suggested
      the presence of a second GPAT in liver mitochondria from mtGPAT(-/-) mice.
      Characterization of this GPAT activity in liver from mtGPAT null mice showed
      that, unlike the mtGPAT activity in wild type samples, activity in mtGPAT
      knockout mitochondria did not prefer palmitoyl-CoA, was sensitive to inactivation
      by NEM, was inhibited by dihydroxyacetone phosphate and polymixin B, was
      temperature-sensitive, and was not activated by acetone. We conclude that a novel
      GPAT (mtGPAT2) with antigenic epitopes similar to those of mtGPAT is detectable
      in mitochondria from the livers of mtGPAT(-/-) mice.

PMID- 14724271
TI  - Pen-2 is sequestered in the endoplasmic reticulum and subjected to ubiquitylation
      and proteasome-mediated degradation in the absence of presenilin.
AB  - The gamma-secretase complex catalyzes intramembrane proteolysis of a number of
      transmembrane proteins, including amyloid precursor protein, Notch, ErbB4, and E
      cadherin. gamma-Secretase is known to contain four major protein constituents:
      presenilin (PS), nicastrin, Aph-1, and Pen-2, all of which are integral membrane
      proteins. There is increasing evidence that the formation of the complex and the
      stability of the individual components are tightly controlled in the cell,
      assuring correct composition of functional complexes. In this report, we
      investigate the topology, localization, and mechanism for destabilization of Pen
      2 in relation to PS function. We show that PS1 regulates the subcellular
      localization of Pen-2: in the absence of PS, Pen-2 is sequestered in the
      endoplasmic reticulum (ER) and not transported to post-ER compartments, where the
      mature gamma-secretase complexes reside. PS deficiency also leads to
      destabilization of Pen-2, which is alleviated by proteasome inhibitors. In
      keeping with this, we show that Pen-2, which adopts a hairpin structure with the
      N and C termini facing the luminal space, is ubiquitylated prior to degradation
      and presumably retrotranslocated from the ER to the cytoplasm. Collectively, our
      data suggest that failure to become incorporated into the gamma-secretase complex
      leads to degradation of Pen-2 through the ER-associated degradation-proteasome
      pathway.

PMID- 14724272
TI  - Regulation of Ca2+-dependent K+ current by alphavbeta3 integrin engagement in
      vascular endothelium.
AB  - Interactions between endothelial cells and extracellular matrix proteins are
      important determinants of endothelial cell signaling. Endothelial adhesion to
      fibronectin through alpha(v)beta(3) integrins or the engagement and aggregation
      of luminal alpha(v)beta(3) receptors by vitronectin triggers Ca2+ influx.
      However, the underlying signaling mechanisms are unknown. The
      electrophysiological basis of alpha(v)beta(3) integrin-mediated changes in
      endothelial cell Ca2+ signaling was studied using whole cell patch clamp and
      microfluorimetry. The resting membrane potential of bovine pulmonary artery
      endothelial cells averaged -60 +/- 3 mV. In the absence of intracellular Ca2+
      buffering, the application of soluble vitronectin (200 microg/ml) resulted in
      activation of an outwardly rectifying K+ current at holding potentials from -50
      to +50 mV. Neither a significant shift in reversal potential (in voltage clamp
      mode) nor a change in membrane potential (in current clamp mode) occurred in
      response to vitronectin. Vitronectin-activated current was significantly
      inhibited by pretreatment with the alpha(v)beta(3) integrin antibody LM609 by
      exchanging extracellular K+ with Cs+ or by the application of iberiotoxin, a
      selective inhibitor of large-conductance, Ca2+-activated K+ channels. With
      intracellular Ca2+ buffered by EGTA in the recording pipette, vitronectin
      activated K+ current was abolished. Fura-2 microfluorimetry revealed that
      vitronectin induced a significant and sustained increase in intracellular Ca2+
      concentration, although vitronectin-induced Ca2+ current could not be detected.
      This is the first report to show that an endothelial cell ion channel is
      regulated by integrin activation, and this K+ current likely plays a crucial role
      in maintaining membrane potential and a Ca2+ driving force during engagement and
      activation of endothelial cell alpha(v)beta(3) integrin.

PMID- 14724273
TI  - Multidimensional NMR identifies the conformational shift essential for catalytic
      competence in the 60-kDa Drosophila melanogaster dUTPase trimer.
AB  - The catalytic mechanism of dUTP pyrophosphatase (dUTPase), responsible for the
      prevention of uracil incorporation into DNA, involves ordering of the flexible C
      terminus of the enzyme. This conformational shift is investigated by
      multidimensional NMR on the Drosophila enzyme. Flexible segments of the
      homotrimer give rise to sharp resonances in the (1)H-(15)N heteronuclear single
      quantum coherence (HSQC) spectra, which are clearly distinguishable from the
      background resonances of the well folded protein globule. Binding of the product
      dUMP or the analogues dUDP and alpha,beta-imino-dUTP to the enzyme induces a
      conformational change reflected in the disappearance of eight sharp resonances.
      This phenomenon is interpreted as nucleotide binding-induced ordering of some
      residues upon the folded protein globule. Three-dimensional (15)N-edited (1)H
      (15)N HSQC total correlation spectroscopy (TOCSY) and (1)H-(15)N HSQC nuclear
      Overhauser effect spectroscopy measurements allowed clear assignment of these
      eight specific resonance peaks. The residues identified correspond to the
      conserved C-terminal sequence motif, indicating that (i) this conformational
      shift is amenable to NMR studies in solution even in the large trimeric molecule
      and (ii) formation of the closed enzyme conformer in the case of the Drosophila
      enzyme does not require the complete triphosphate chain of the substrate. NMR
      titration of the enzyme with the nucleotide ligands as well as kinetic data
      indicated significant deviation from the model of independent active sites within
      the homotrimer. The results suggest allosterism in the eukaryotic dUTPase.

PMID- 14724274
TI  - Altered active site flexibility and a structural metal-binding site in eukaryotic
      dUTPase: kinetic characterization, folding, and crystallographic studies of the
      homotrimeric Drosophila enzyme.
AB  - dUTPase is responsible for preventive DNA repair via exclusion of uracil.
      Developmental regulation of the Drosophila enzyme is suggested to be involved in
      thymine-less apoptosis. Here we show that in addition to conserved dUTPase
      sequence motifs, the gene of Drosophila enzyme codes for a unique Ala-Pro-rich
      segment. Kinetic and structural analyses of the recombinant protein and a
      truncation mutant show that the Ala-Pro segment is flexible and has no regulatory
      role in vitro. The homotrimer enzyme unfolds reversibly as a trimeric entity with
      a melting temperature of 54 degrees C, 23 degrees C lower than Escherichia coli
      dUTPase. In contrast to the bacterial enzyme, Mg(2+) binding modulates
      conformation of fly dUTPase, as identified by spectroscopy and by increment in
      melting temperature. A single well folded, but inactive, homotrimeric core domain
      is generated through three distinct steps of limited trypsinolysis. In fly, but
      not in bacterial dUTPase, binding of the product dUMP induces protection against
      proteolysis at the tryptic site reflecting formation of the catalytically
      competent closed conformer. Crystallographic analysis argues for the presence of
      a stable monomer of Drosophila dUTPase in crystal phase. The significant
      differences between prototypes of eukaryotic and prokaryotic dUTPases with
      respect to conformational flexibility of the active site, substrate specificity,
      metal ion binding, and oligomerization in the crystal phase are consistent with
      alteration of the catalytic mechanism and hydropathy of subunit interfaces.

PMID- 14724275
TI  - Selective expression and functional characteristics of three mammalian hyaluronan
      synthases in oncogenic malignant transformation.
AB  - Malignant transformation of fibroblasts and epithelial cells is often accompanied
      by increased hyaluronan production and accumulation. Despite recent progress in
      the study of hyaluronan biosynthesis, the mechanisms underlying the
      transformation-induced overproduction of hyaluronan have not been elucidated.
      Here we report that activity and transcriptional levels of hyaluronan synthase
      (HAS) significantly increased after oncogenic malignant transformation of a rat
      3Y1 fibroblast cell line. Of three HAS isoforms (HAS1, HAS2, and HAS3), only HAS2
      gene expression was increased in the v-Ha-ras transformed 3Y1 cells, which show
      less malignancy. In contrast, both HAS1 and HAS2 expressions were elevated in the
      highly malignant cells transformed with v-src and/or v-fos. To assess the
      contribution of HAS expression to the oncogenic malignant transformation, we
      established stable cell transfectants expressing sense and antisense HAS genes.
      Antisense suppression of the HAS2 expression significantly decreased hyaluronan
      production in the cells transformed by the oncogenic v-Ha-ras and eventually led
      to a reduction in tumorigenicity in the rat peritoneum. The introduction of the
      HAS1 and HAS2 genes promoted the growth of subcutaneous tumors in a manner
      dependent on the levels of hyaluronan synthesis. Significant growth promotion was
      observed within a wide range of HAS1 expression. In contrast, the growth
      stimulation was only seen within a narrow range of HAS2 expression, and high
      levels of HAS2 expression even inhibited tumor growth. These results suggest that
      proper regulation of the expression of each HAS isoform is required for optimal
      malignant transformation and tumor growth.

PMID- 14724276
TI  - Peroxidase activity of cyclooxygenase-2 (COX-2) cross-links beta-amyloid (Abeta)
      and generates Abeta-COX-2 hetero-oligomers that are increased in Alzheimer's
      disease.
AB  - Oxidative stress is associated with the neuropathology of Alzheimer's disease. We
      have previously shown that human Abeta has the ability to reduce Fe(III) and
      Cu(II) and produce hydrogen peroxide coupled with these metals, which is
      correlated with toxicity against primary neuronal cells. Cyclooxygenase (COX)-2
      expression is linked to the progression and severity of pathology in AD. COX is a
      heme-containing enzyme that produces prostaglandins, and the enzyme also
      possesses peroxidase activity. Here we investigated the possibility of direct
      interaction between human Abeta and COX-2 being mediated by the peroxidase
      activity. Human Abeta formed dimers when it was reacted with COX-2 and hydrogen
      peroxide. Moreover, the peptide formed a cross-linked complex directly with COX
      2. Such cross-linking was not observed with rat Abeta, and the sole tyrosine
      residue specific for human Abeta might therefore be the site of cross-linking.
      Similar complexes of Abeta and COX-2 were detected in post-mortem brain samples
      in greater amounts in AD tissue than in age-matched controls. COX-2-mediated
      cross-linking may inhibit Abeta catabolism and possibly generate toxic
      intracellular forms of oligomeric Abeta.

PMID- 14724277
TI  - Aggregation of the Acylphosphatase from Sulfolobus solfataricus: the folded and
      partially unfolded states can both be precursors for amyloid formation.
AB  - Protein aggregation is associated with a number of human pathologies including
      Alzheimer's and Creutzfeldt-Jakob diseases and the systemic amyloidoses. In this
      study, we used the acylphosphatase from the hyperthermophilic Archaea Sulfolobus
      solfataricus (Sso AcP) to investigate the mechanism of aggregation under
      conditions in which the protein maintains a folded structure. In the presence of
      15-25% (v/v) trifluoroethanol, Sso AcP was found to form aggregates able to bind
      specific dyes such as thioflavine T, Congo red, and 1-anilino-8
      naphthalenesulfonic acid. The presence of aggregates was confirmed by circular
      dichroism and dynamic light scattering. Electron microscopy revealed the presence
      of small aggregates generally referred to as amyloid protofibrils. The monomeric
      form adopted by Sso AcP prior to aggregation under these conditions retained
      enzymatic activity; in addition, folding was remarkably faster than unfolding.
      These observations indicate that Sso AcP adopts a folded, although possibly
      distorted, conformation prior to aggregation. Most important, aggregation
      appeared to be 100-fold faster than unfolding under these conditions. Although
      aggregation of Sso AcP was faster at higher trifluoroethanol concentrations, in
      which the protein adopted a partially unfolded conformation, these findings
      suggest that the early events of amyloid fibril formation may involve an
      aggregation process consisting of the assembly of protein molecules in their
      folded state. This conclusion has a biological relevance as globular proteins
      normally spend most of their lifetime in folded structures.

PMID- 14724278
TI  - Crystal structure of imidazole glycerol-phosphate dehydratase: duplication of an
      unusual fold.
AB  - Imidazole glycerol-phosphate dehydratase (IGPD) catalyzes the sixth step of
      histidine biosynthesis. The enzyme is of fundamental biochemical interest,
      because it catalyzes removal of a non-acidic hydrogen atom in the dehydration
      reaction. It is also a potential target for development of herbicides. IGPD is a
      metalloenzyme in which transition metals induce aggregation and are required for
      catalysis. Addition of 1 equivalent of Mn(2+)/subunit is shown by analytical
      ultracentrifugation to induce the formation of 24-mers from trimeric IGPD. Two
      histidine-rich motifs may participate in metal binding and aggregation. The 2.3-A
      crystal structure of metal-free trimeric IGPD from the fungus Filobasidiella
      neoformans reveals a novel fold containing an internal repeat, apparently the
      result of gene duplication. The 95-residue alpha/beta half-domain occurs in a few
      other proteins, including the GHMP kinase superfamily (galacto-homoserine
      mevalonate-phosphomevalonate), but duplication to form a compact domain has not
      been seen elsewhere. Conserved residues cluster at two types of sites in the
      trimer, each site containing a conserved histidine-rich motif. A model is
      proposed for the intact, active 24-mer in which all highly conserved residues,
      including the histidine-rich motifs in both the N- and C-terminal halves of the
      polypeptide, cluster at a common site between trimers. This site is a candidate
      for the active site and also for metal binding leading to aggregation of trimers.
      The structure provides a basis for further studies of enzyme function and
      mechanism and for development of more potent and specific herbicides.

PMID- 14724279
TI  - Structure of a hydroxyproline (Hyp)-arabinogalactan polysaccharide from
      repetitive Ala-Hyp expressed in transgenic Nicotiana tabacum.
AB  - A synthetic gene encoding the fusion protein (Ala-Hyp)(51)-enhanced green
      fluorescent protein expressed in Nicotiana tabacum cells produced a fusion
      glycoprotein with all proline residues hydroxylated and substituted with an
      arabinogalactan polysaccharide. Alkaline hydrolysis of the fusion glycoprotein
      yielded a population of hydroxyproline (Hyp)-arabinogalactan polysaccharides
      ranging in size from 13 to 26 saccharide residues/Hyp, with a median size of 15
      17 residues. We isolated a 15-residue Hyp-arabinogalactan for structure
      determination by sugar analyses and one- and two-dimensional nuclear magnetic
      resonance techniques that provided the assignment of proton and carbon signals of
      a small polysaccharide O-linked to the hydroxyl group of Hyp. The polysaccharide
      consisted of a 1,3-linked beta-D-Galp backbone with a single 1,6-linked beta-D
      Galp "kink." The backbone had two side chains of Galp substituted at position 3
      with an arabinose di- or trisaccharide and at position 6 with glucuronic acid or
      rhamnosyl glucuronic acid. Energy-minimized space-filling molecular models showed
      hydrogen bonding within polysaccharides attached to repetitive Ala-Hyp and also
      between polysaccharides and the peptide backbone. Polysaccharides distorted the
      peptide Ramachandran angles consistent with the circular dichroic spectra of
      isolated (Ala-Hyp)(51) and its reversion to a polyproline II-like helix after
      deglycosylation. This first complete structure of a Hyp-arabinogalactan
      polysaccharide shows that computer-based molecular modeling of Hyp-rich
      glycoproteins is now feasible and supports the suggestion that small repetitive
      subunits comprise larger arabinogalactan polysaccharides.

PMID- 14724280
TI  - A novel protein activity mediates DNA binding of an ATR-ATRIP complex.
AB  - The function of the ATR (ataxia-telangiectasia mutated and Rad3-related)-ATRIP
      (ATR-interacting protein) protein kinase complex is central to the cellular
      response to replication stress and DNA damage. In order to better understand the
      function of this complex, we have studied its interaction with DNA. We find that
      both ATR and ATRIP associate with chromatin in vivo, and they exist as a large
      molecular weight complex that can bind single-stranded (ss)DNA cellulose in
      vitro. Although replication protein A (RPA) is sufficient for the recruitment of
      ATRIP to ssDNA, we show that a distinct ATR-ATRIP complex is able to bind to DNA
      with lower affinity in the absence of RPA. In this latter complex, we show that
      neither ATR nor ATRIP are able to bind DNA individually, nor do they bind DNA in
      a cooperative manner. However, the addition of HeLa nuclear extract is able to
      reconstitute the DNA binding of both ATR and ATRIP, suggesting the requirement
      for an additional protein activity. We also show that ATR is necessary for ATRIP
      to bind DNA in this low affinity mode and to form a large DNA binding complex.
      These observations suggest that there are at least two in vitro ATR-ATRIP DNA
      binding complexes, one which binds DNA with high affinity in an RPA-dependent
      manner and a second, which binds DNA with lower affinity in an RPA-independent
      manner but which requires an as of yet unidentified protein.

PMID- 14724281
TI  - The vesicular acetylcholine transporter interacts with clathrin-associated
      adaptor complexes AP-1 and AP-2.
AB  - In neuronal cells the neurotransmitter acetylcholine is transferred from the
      cytoplasm into synaptic vesicles by the vesicular acetylcholine transporter
      (VAChT). The cytoplasmic tail of VAChT has been shown to contain signals that
      direct its sorting and trafficking. The role of clathrin-associated protein
      complexes in VAChT sorting to synaptic vesicles has been examined. A fusion
      protein between the VAChT cytoplasmic tail and glutathione S-transferase was used
      to identify VAChT-clathrin-associated protein adaptor protein 1, adaptor protein
      2 and adaptor protein 180 complexes from a rat brain extract. In vivo
      coimmunoprecipitation confirmed adaptin alpha and adaptin gamma complexes, but
      adaptor protein 180 complexes were not detected by this technique. Deletion and
      site directed mutagenesis show that the VAChT cytoplasmic tail contains multiple
      trafficking signals. These include a non-classical tyrosine motif that serves as
      the signal for adaptin alpha and a dileucine motif that serves as the signal for
      adaptin gamma. A classical tyrosine motif is also involved in VAChT trafficking,
      but does not interact with any known adaptor proteins. There appear to be two
      endocytosis motifs, one involving the adaptor protein 1 binding site and the
      other involving the adaptor protein 2 binding site. These results suggest a
      complex trafficking pathway for VAChT.

PMID- 14724283
TI  - Link protein has greater affinity for versican than aggrecan.
AB  - The function of link protein in stabilizing the interaction between aggrecan and
      hyaluronan to form aggrecan aggregates, via the binding of link protein to the
      aggrecan G1 domain and hyaluronan, is well established. However, it is not known
      whether link protein can function with similar avidity with versican, another
      member of the large hyaluronan-binding proteoglycan family that also binds to
      hyaluronan via its G1 domain. To address this issue, we have compared the
      interaction of the versican and aggrecan G1 domains with link protein and
      hyaluronan using recombinant proteins expressed in insect cells and BIAcore
      analysis. The results showed that link protein could significantly improve the
      binding of both G1 domains to hyaluronan and that its interaction with VG1 is of
      a higher affinity than that with AG1. These observations suggest that link
      protein may function as a stabilizer of the interaction, not only between
      aggrecan and hyaluronan in cartilage, but also between versican and hyaluronan in
      many tissues.

PMID- 14724282
TI  - A novel human beta1,3-N-acetylgalactosaminyltransferase that synthesizes a unique
      carbohydrate structure, GalNAcbeta1-3GlcNAc.
AB  - We found, using a BLAST search, a novel human gene (GenBank trade mark accession
      number BC029564) that possesses beta3-glycosyltransferase motifs. The full-length
      open reading frame consists of 500 amino acids and encodes a typical type II
      membrane protein. This enzyme has a domain containing beta1,3-glycosyltransferase
      motifs, which are widely conserved in the beta1,3-galactosyltransferase and
      beta1,3-N-acetylglucosaminyltransferase families. The putative catalytic domain
      was expressed in human embryonic kidney 293T cells as a soluble protein. Its N
      acetylgalactosaminyltransferase activity was observed when N-acetylglucosamine
      (GlcNAc) beta1-O-benzyl was used as an acceptor substrate. The enzyme product was
      determined to have a beta1,3-linkage by NMR spectroscopic analysis, and was
      therefore named beta1,3-N-acetylgalactosaminyltransferase-II (beta3GalNAc-T2).
      The acceptor substrate specificity of beta3GalNAc-T2 was examined using various
      oligosaccharide substrates. Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-O-para
      nitrophenyl (core 2-pNP) was the best acceptor substrate for beta3GalNAc-T2,
      followed by GlcNAcbeta1-4GlcNAcbeta1-O-benzyl, and GlcNAcbeta1-6GalNAcalpha1-O
      para-nitrophenyl (core 6-pNP), among the tested oligosaccharide substrates.
      Quantitative real time PCR analysis revealed that the beta3Gal-NAc-T2 transcripts
      was restricted in its distribution mainly to the testis, adipose tissue, skeletal
      muscle, and ovary. Its putative orthologous gene, mbeta3GalNAc-T2, was also found
      in a data base of mouse expressed sequence tags. In situ hybridization analysis
      with mouse testis showed that the transcripts are expressed in germ line cells.
      beta3GalNAc-T2 efficiently transferred GalNAc to N-glycans of fetal calf fetuin,
      which was treated with neuraminidase and beta-galactosidase. However, it showed
      no activity toward any glycolipid examined. Although the GalNAcbeta1-3GlcNAcbeta1
      R structure has not been reported in humans or other mammals, we have discovered
      a novel human glycosyltransferase producing this structure on N- and O-glycans.

PMID- 14724284
TI  - Protein radical formation during lactoperoxidase-mediated oxidation of the
      suicide substrate glutathione: immunochemical detection of a lactoperoxidase
      radical-derived 5,5-dimethyl-1-pyrroline N-oxide nitrone adduct.
AB  - A novel anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that
      specifically recognizes protein radical-derived DMPO nitrone adducts has been
      developed. In this study, we employed this new approach, which combines the
      specificity of spin trapping and the sensitivity of antigen-antibody
      interactions, to investigate protein radical formation from lactoperoxidase
      (LPO). When LPO reacted with GSH in the presence of DMPO, we detected an LPO
      radical-derived DMPO nitrone adduct using enzyme-linked immunosorbent assay and
      Western blotting. The formation of this nitrone adduct depended on the
      concentrations of GSH, LPO, and DMPO as well as pH values, and GSH could not be
      replaced by H(2)O(2). The level of this nitrone adduct was decreased
      significantly by azide, catalase, ascorbate, iodide, thiocyanate, phenol, or
      nitrite. However, its formation was unaffected by chemical modification of free
      cysteine, tyrosine, and tryptophan residues on LPO. ESR spectra showed that a
      glutathiyl radical was formed from the LPO/GSH/DMPO system, but no protein
      radical adduct could be detected by ESR. Its formation was decreased by azide,
      catalase, ascorbate, iodide, or thiocyanate, whereas phenol or nitrite increased
      it. GSH caused marked changes in the spectrum of compound II of LPO, indicating
      that GSH binds to the heme of compound II, whereas phenol or nitrite prevented
      these changes and reduced compound II back to the native enzyme. GSH also dose
      dependently inhibited the peroxidase activity of LPO as determined by measuring
      2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation. Taken together,
      these results demonstrate that the GSH-dependent LPO radical formation is
      mediated by the glutathiyl radical, possibly via the reaction of the glutathiyl
      radical with the heme of compound II to form a heme-centered radical trapped by
      DMPO.

PMID- 14724285
TI  - Trypanosoma brucei plasma membrane-type Ca(2+)-ATPase 1 (TbPMC1) and 2 (TbPMC2)
      genes encode functional Ca(2+)-ATPases localized to the acidocalcisomes and
      plasma membrane, and essential for Ca(2+) homeostasis and growth.
AB  - Trypanosoma brucei adaptation and survival in its host involve integrated
      regulation of Ca(2+) pumps (Ca(2+)-ATPases), which are essential in calcium ion
      homeostasis. Here we report the cloning and sequencing of two genes (TbPMC1 and
      TbPMC2) encoding plasma membrane-type Ca(2+)-ATPases (PMCAs) of T. brucei, an
      agent of African trypanosomiasis. Indirect immunofluorescence analysis using
      antibodies against the proteins and against epitope tags introduced into each
      protein showed that TbPMC1 co-localized with the vacuolar H(+)-pyrophosphatase to
      the acidocalcisomes while TbPMC2 localized to the plasma membrane. Northern and
      Western blot analyses revealed that TbPMC1 and TbPMC2 are up-regulated during
      blood stages. TbPMC1 and TbPMC2 suppressed the Ca(2+) hypersensitivity of a
      mutant of S. cerevisiae that has a defect in vacuolar Ca(2+) accumulation. T.
      brucei Ca(2+)-ATPase genes were functionally characterized by using double
      stranded RNA interference (RNAi) methodology to produce inducible Ca(2+)-ATPase
      deficient procyclic forms. Similar results were obtained with bloodstream form
      trypomastigotes, except that the RNAi system was leaky and mRNA and protein
      levels recovered with time. The induction of dsRNA (RNAi) caused gross
      morphological alterations, and growth inhibition of procyclic forms. Induction of
      RNAi against TbPMC1 but not against TbPMC2 caused elevated levels of cytosolic
      Ca(2+) and decreased mobilization of Ca(2+) from intracellular stores following
      ionophore addition. These results establish that T. brucei PMCA-Ca(2+)-ATPases
      are essential for parasite viability and validate them as targets for drug
      development.

PMID- 14724286
TI  - Human hepatitis B virus-X protein alters mitochondrial function and physiology in
      human liver cells.
AB  - The hepatitis B virus-X protein (HBx) regulates fundamental aspects of
      mitochondrial physiology. We show that HBx down-regulates mitochondrial enzymes
      involved in electron transport in oxidative phosphorylation (complexes I, III,
      IV, and V) and sensitizes the mitochondrial membrane potential in a hepatoma cell
      line. HBx also increases the level of mitochondrial reactive oxygen species and
      lipid peroxide production. HBx does not activate apoptotic signaling, although it
      sensitizes hepatoma cells to apoptotic signaling, which is dependent on reactive
      oxygen species. Increased intrahepatic lipid peroxidation in HBx transgenic mice
      demonstrated that oxidative injury occurs as a direct result of HBx expression.
      Therefore, we conclude that mitochondrial dysfunction is a crucial
      pathophysiological factor in HBx-expressing hepatoma cells and provides an
      experimental rationale in the investigation of mitochondrial function in rapidly
      renewed tissues, as in hepatocellular carcinomas.

PMID- 14724287
TI  - Ca2+-induced rolling of tropomyosin in muscle thin filaments: the alpha- and beta
      band hypothesis revisited.
AB  - Tropomyosin is a filamentous coiled-coil protein directly involved in the
      regulation of the actomyosin interaction responsible for muscle contraction: it
      transmits the local calcium-induced conformational change in troponin to the
      helical array of myosin-binding sites on the surface of the actin filament.
      McLachlan and Stewart (McLachlan, A. D., and Stewart, M. (1976) J. Mol. Biol.
      103, 271-298) proposed that the tropomyosin coiled-coil structure can be divided
      into 14 alternating 19- to 20-residue "alpha- and beta-bands," which could act as
      alternate 7-fold sets of sites for specific binding to actin in the different
      conformational states of the regulated thin filament. Here we present the first
      direct experimental evidence in support of the alpha- and beta-band hypothesis:
      we analyze the acrylamide quenching of the fluorescence of mutant tropomyosins
      containing 5-hydroxytryptophan residues at different positions along the coiled
      coil structure under a variety of conditions (alone, complexed with actin, and
      complexed with actin and troponin with or without Ca(2+)). We show that
      fluorescent probes placed in the alpha-bands become less solvent-exposed in the
      absence of calcium, whereas those in the beta-bands become less solvent-exposed
      in the presence of calcium. A model in which the tropomyosin coiled-coil rolls
      across the actin surface in response to Ca(2+)-binding to troponin most easily
      explains these observations.

PMID- 14724288
TI  - Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced
      transformation.
AB  - The c-myc proto-oncogene encodes a ubiquitous transcription factor involved in
      the control of cell growth and differentiation and implicated in inducing
      tumorigenesis. Understanding the function of c-Myc and its role in cancer depends
      upon the identification of c-Myc target genes. Heat shock protein 90 (HSP90) is
      involved in the folding of proteins such as signal transduction molecules (Src,
      Raf1, cdk4) and steroid receptors and in enhancing the activity of telomerase and
      nitric-oxide synthase. Here we show that c-Myc directly activates HSP90A
      transcription. c-Myc-mediated induction of HSP90A transcription occurs in
      different tissues, is independent of cell proliferation, and is mediated by a c
      Myc binding site in the proximal promoter region of HSP90A gene. Overexpression
      of HSP90A in Rat1a cells induces transformation. Short interference RNA of
      HSP90A/Hsp86alpha reduces transformation activity in HeLa and RatMyc cells. These
      results indicate that by induction of HSP90A c-Myc may control the activity of
      multiple signal pathways involved in cellular transformation.

PMID- 14724289
TI  - The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of
      the secreted phosphatidylethanolamine-binding protein, possesses a new biological
      activity on cardiac physiology.
AB  - Phosphatidylethanolamine-binding protein (PEBP), alternatively named Raf-1 kinase
      inhibitor protein, is the precursor of the hippocampal cholinergic
      neurostimulating peptide (HCNP) corresponding to its natural N-terminal fragment,
      previously described to be released by hippocampal neurons. PEBP is a soluble
      cytoplasmic protein, also associated with plasma and reticulum membranes of
      numerous cell types. In the present report, using biochemistry and cell biology
      techniques, we report for the first time the presence of PEBP in bovine
      chromaffin cell, a well described secretion model. We have examined its presence
      at the subcellular level and characterized this protein on both secretory granule
      membranes and intragranular matrix. In addition, its presence in bovine
      chromaffin cell and platelet exocytotic medium, as well as in serum, was reported
      showing that it is secreted. Like many other proteins that lack signal sequence,
      PEBP may be secreted through non-classic signal secretory mechanisms, which could
      be due to interactions with granule membrane lipids and lipid rafts. By two
      dimensional liquid chromatography-tandem mass spectrometry, HCNP was detected
      among the intragranular matrix components. The observation that PEBP and HCNP
      were secreted with catecholamines into the circulation prompted us to investigate
      endocrine effects of this peptide on cardiovascular system. By using as bioassay
      an isolated and perfused frog (Rana esculenta) heart preparation, we show here
      that HCNP acts on the cardiac mechanical performance exerting a negative
      inotropism and counteracting the adrenergic stimulation of isoproterenol. All
      together, these data suggest that PEBP and HCNP might be considered as new
      endocrine factors involved in cardiac physiology.

PMID- 14724290
TI  - Pharmacological enhancement of beta-hexosaminidase activity in fibroblasts from
      adult Tay-Sachs and Sandhoff Patients.
AB  - Tay-Sachs and Sandhoff diseases are lysosomal storage disorders that result from
      an inherited deficiency of beta-hexosaminidase A (alphabeta). Whereas the acute
      forms are associated with a total absence of hexosaminidase A and early death,
      the chronic adult forms exist with activity and protein levels of approximately
      5%, and unaffected individuals have been found with only 10% of normal levels.
      Surprisingly, almost all disease-associated missense mutations do not affect the
      active site of the enzyme but, rather, inhibit its ability to obtain and/or
      retain its native fold in the endoplasmic reticulum, resulting in its retention
      and accelerated degradation. By growing adult Tay-Sachs fibroblasts in culture
      medium containing known inhibitors of hexosaminidase we have raised the residual
      protein and activity levels of intralysosomal hexosaminidase A well above the
      critical 10% of normal levels. A similar effect was observed in fibroblasts from
      an adult Sandhoff patient. We propose that these hexosaminidase inhibitors
      function as pharmacological chaperones, enhancing the stability of the native
      conformation of the enzyme, increasing the amount of hexosaminidase A capable of
      exiting the endoplasmic reticulum for transport to the lysosome. Therefore,
      pharmacological chaperones could provide a novel approach to the treatment of
      adult Tay-Sachs and possibly Sandhoff diseases.

PMID- 14724291
TI  - Nerve growth factor-dependent survival of CESS B cell line is mediated by
      increased expression and decreased degradation of MAPK phosphatase 1.
AB  - The sIgG(+) lymphoblastoid B cell line CESS spontaneously produces a high amount
      of nerve growth factor (NGF) and expresses both high affinity (p140(Trk-A)) and
      low affinity (p75(NTR)) NGF receptors. Autocrine production of NGF maintains the
      survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme
      able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and
      caspase activation. In this paper, we show that NGF induces transcriptional
      activation and synthesis of MAPK phosphatase 1 (MKP-1), a dual specificity
      phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2
      phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing
      its degradation through the proteasome pathway. Following NGF stimulation, MKP-1
      protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK
      in this compartment. Incubation of CESS cells with MKP-1-specific antisense
      oligonucleotides induces cell death, which was not prevented by exogenous NGF. By
      contrast, overexpression of native MKP-1, but not of its catalytically impaired
      form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the
      molecular mechanisms underlying the survival function of NGF in CESS B cell line
      predominantly consist in maintaining elevated levels of MKP-1 protein, which
      controls p38 MAPK activation.

PMID- 14724292
TI  - Molecular mechanisms of the effect of herpesvirus saimiri protein StpC on the
      signaling pathway leading to NF-kappaB activation.
AB  - Herpesvirus saimiri (Saimiriine herpesvirus-2) causes lethal T
      lymphoproliferative diseases in the susceptible species and transforms T
      lymphocytes to continuous growth in vitro. H. saimiri-induced transformation of T
      cells is becoming an important experimental tool of biomedical research. Two
      proteins of H. saimiri subgroup C, Tip and StpC, are essential for T cell
      transformation by this virus. It has been shown previously that StpC transforms
      fibroblasts, activates NF-kappaB, and binds to tumor necrosis factor (TNF)
      receptor-associated factor (TRAF) proteins, but the molecular mechanism of its
      action remains insufficiently understood. This study further characterized the
      effect of StpC on NF-kappaB. First, StpC activates NF-kappaB via the consensus
      pathway involving activation of I-kappaB kinase and subsequent phosphorylation
      and degradation of I-kappaB in both T lymphoid and epithelial cells. Second,
      triggering of this pathway by StpC in both T lymphoid and epithelial cells is
      dependent on the presence of functional NF-kappaB-inducing kinase (NIK). Third,
      StpC physically interacts with TRAF in epithelial cells, and the effect of StpC
      on NF-kappaB activity in these cells requires the presence of functional TRAF.
      Finally the effect of StpC is completely independent of TNF-alpha, a well
      described stimulus of NF-kappaB activity. Moreover it appears that StpC uncouples
      stimulation of NF-kappaB activity from TNF-alpha stimulation. Overall these
      results argue that the effect of StpC on NF-kappaB is similar to the effects of
      other viral proteins, "usurping" the TRAF/NIK/I-kappaB kinase pathway, and
      reinforce the notion that the role of StpC in cell transformation by H. saimiri
      may be mediated by signaling that results in NF-kappaB activation.

PMID- 14724294
TI  - Catalytic asymmetric synthesis of all-carbon quaternary stereocenters.
AB  - Only a few catalytic asymmetric C-C bond-forming reactions have been shown to be
      useful for constructing all-carbon quaternary stereocenters. This Perspective
      examines the current state of such methods.

PMID- 14724293
TI  - Calcium influx through hyperpolarization-activated cation channels (I(h)
      channels) contributes to activity-evoked neuronal secretion.
AB  - The hyperpolarization-activated cation channels (I(h)) play a distinct role in
      rhythmic activities in a variety of tissues, including neurons and cardiac cells.
      In the present study, we investigated whether Ca(2+) can permeate through the
      hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells
      and I(h) channels in dorsal root ganglion (DRG) neurons. Using combined
      measurements of whole-cell currents and fura-2 Ca(2+) imaging, we found that
      there is a Ca(2+) influx in proportion to I(h) induced by hyperpolarization in
      HEK293 cells. The I(h) channel blockers Cs(+) and ZD7288 inhibit both HCN current
      and Ca(2+) influx. Measurements of the fractional Ca(2+) current showed that it
      constitutes 0.60 +/- 0.02% of the net inward current through HCN4 at -120 mV.
      This fractional current is similar to that of the low Ca(2+)-permeable AMPA-R
      (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) channels in
      Purkinje neurons. In DRG neurons, activation of I(h) for 30 s also resulted in a
      Ca(2+) influx and an elevated action potential-induced secretion, as assayed by
      the increase in membrane capacitance. These results suggest a functional
      significance for I(h) channels in modulating neuronal secretion by permitting
      Ca(2+) influx at negative membrane potentials.

PMID- 14724295
TI  - Searching for intellectual turning points: progressive knowledge domain
      visualization.
AB  - This article introduces a previously undescribed method progressively visualizing
      the evolution of a knowledge domain's cocitation network. The method first
      derives a sequence of cocitation networks from a series of equal-length time
      interval slices. These time-registered networks are merged and visualized in a
      panoramic view in such a way that intellectually significant articles can be
      identified based on their visually salient features. The method is applied to a
      cocitation study of the superstring field in theoretical physics. The study
      focuses on the search of articles that triggered two superstring revolutions.
      Visually salient nodes in the panoramic view are identified, and the nature of
      their intellectual contributions is validated by leading scientists in the field.
      The analysis has demonstrated that a search for intellectual turning points can
      be narrowed down to visually salient nodes in the visualized network. The method
      provides a promising way to simplify otherwise cognitively demanding tasks to a
      search for landmarks, pivots, and hubs.

PMID- 14724297
TI  - "Me-too" products--friend or foe?

PMID- 14724296
TI  - Complex and dynamic redistribution of NF-kappaB signaling intermediates in
      response to T cell receptor stimulation.
AB  - The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T
      cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell
      (APC) junction in response to antigen stimulation. We demonstrate that there is a
      surprisingly complex relocalization process that brings PKC and Bcl10, two
      intermediates in TCR activation of NF-kappaB, to the cytoplasmic face of the c
      SMAC. TCR activation causes enrichment of PKC at the c-SMAC, followed by Bcl10
      relocalization to punctate cytoplasmic structures, often at sites distant from
      the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming
      enriched at the c-SMAC. TCR activation of NF-kappaB therefore involves the
      dynamic relocalization of multiple signaling intermediates, with distinct phases
      proximal to and distant from the c-SMAC.

PMID- 14724298
TI  - Bacterial infection and MALT lymphoma.

PMID- 14724299
TI  - Tapeworms and seizures--treatment and prevention.

PMID- 14724300
TI  - Influenza vaccine--outmaneuvering antigenic shift and drift.

PMID- 14724301
TI  - A polymer-based, paclitaxel-eluting stent in patients with coronary artery
      disease.
AB  - BACKGROUND: Restenosis after coronary stenting necessitates repeated percutaneous
      or surgical revascularization procedures. The delivery of paclitaxel to the site
      of vascular injury may reduce the incidence of neointimal hyperplasia and
      restenosis. METHODS: At 73 U.S. centers, we enrolled 1314 patients who were
      receiving a stent in a single, previously untreated coronary-artery stenosis
      (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective,
      randomized, double-blind study. A total of 652 patients were randomly assigned to
      receive a bare-metal stent, and 662 to receive an identical-appearing, slow
      release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was
      prespecified at nine months in 732 patients. RESULTS: In terms of base-line
      characteristics, the two groups were well matched. Diabetes mellitus was present
      in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and
      the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were
      implanted per patient. The rate of ischemia-driven target-vessel
      revascularization at nine months was reduced from 12.0 percent with the
      implantation of a bare-metal stent to 4.7 percent with the implantation of a
      paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval,
      0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0
      percent of the group that received a paclitaxel-eluting stent, as compared with
      11.3 percent of the group that received a bare-metal stent (relative risk, 0.27;
      95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic
      restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel
      eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46;
      P<0.001). The nine-month composite rates of death from cardiac causes or
      myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent
      thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group
      that received a paclitaxel-eluting stent and the group that received a bare-metal
      stent. CONCLUSIONS: As compared with bare-metal stents, the slow-release, polymer
      based, paclitaxel-eluting stent is safe and markedly reduces the rates of
      clinical and angiographic restenosis at nine months.

PMID- 14724302
TI  - A clinical trial of abciximab in elective percutaneous coronary intervention
      after pretreatment with clopidogrel.
AB  - BACKGROUND: Whether the glycoprotein IIb/IIIa inhibitor abciximab is beneficial
      in patients undergoing elective percutaneous coronary intervention after
      pretreatment with clopidogrel is unknown. METHODS: We enrolled 2159 patients with
      coronary artery disease who underwent a percutaneous coronary intervention: 1079
      patients were randomly assigned in a double-blind manner to receive abciximab and
      1080 patients to receive placebo. All patients were pretreated with a 600-mg dose
      of clopidogrel at least two hours before the procedure. The primary end point of
      the trial was the composite of death, myocardial infarction, and urgent target
      vessel revascularization within 30 days after randomization. RESULTS: The
      incidence of the primary end point was 4 percent (45 patients) in the abciximab
      group, as compared with 4 percent (43 patients) in the placebo group (relative
      risk, 1.05; 95 percent confidence interval, 0.69 to 1.59; P=0.82). Most adverse
      events were myocardial infarctions: the incidence was 4 percent (40 patients) in
      the abciximab group and 4 percent (41 patients) in the placebo group (P=0.91).
      Twelve patients (1 percent) in the abciximab group and eight patients (1 percent)
      in the placebo group had major bleeding complications (P=0.37). Profound
      thrombocytopenia occurred in 10 patients (1 percent) in the abciximab group but
      in none in the placebo group (P=0.002). CONCLUSIONS: Our data suggest that in
      patients at low-to-intermediate risk who undergo elective percutaneous coronary
      intervention after pretreatment with a high loading dose of clopidogrel,
      abciximab is associated with no clinically measurable benefit within the first 30
      days.

PMID- 14724303
TI  - Immunoproliferative small intestinal disease associated with Campylobacter
      jejuni.
AB  - BACKGROUND: Immunoproliferative small intestinal disease (also known as alpha
      chain disease) is a form of lymphoma that arises in small intestinal mucosa
      associated lymphoid tissue (MALT) and is associated with the expression of a
      monotypic truncated immunoglobulin alpha heavy chain without an associated light
      chain. Early-stage disease responds to antibiotics, suggesting a bacterial
      origin. We attempted to identify a causative agent. METHODS: We performed
      polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ
      hybridization, and immunohistochemical studies on intestinal-biopsy specimens
      from a series of patients with immunoproliferative small intestinal disease.
      RESULTS: Analysis of frozen intestinal tissue obtained from an index patient with
      immunoproliferative small intestinal disease who had a dramatic response to
      antibiotics revealed the presence of Campylobacter jejuni. A follow-up
      retrospective analysis of archival intestinal-biopsy specimens disclosed
      campylobacter species in four of six additional patients with immunoproliferative
      small intestinal disease. CONCLUSIONS: These results indicate that campylobacter
      and immunoproliferative small intestinal disease are associated and that C.
      jejuni should be added to the growing list of human pathogens responsible for
      immunoproliferative states.

PMID- 14724304
TI  - A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral
      cysticercosis.
AB  - BACKGROUND: Neurocysticercosis is the main cause of adult-onset seizures in the
      developing world. Whether therapy with antiparasitic agents results in improved
      seizure control has been questioned because of the lack of adequate, controlled
      studies. METHODS: We conducted a double-blind, placebo-controlled trial in which
      120 patients who had living cysticerci in the brain and seizures treated with
      antiepileptic drugs were randomly assigned to receive either 800 mg of
      albendazole per day and 6 mg of dexamethasone per day for 10 days (60 patients)
      or two placebos (60 patients). The patients were followed for 30 months or until
      they had been seizure-free for 6 months after the doses of the antiepileptic
      drugs had been tapered. The efficacy of treatment was measured as the decrease in
      the number of seizures after treatment. RESULTS: In the albendazole group, there
      was a 46 percent reduction in the number of seizures (95 percent confidence
      interval, -74 to 83 percent) during months 2 to 30 after treatment. This
      reduction, which was not statistically significant, was composed of a
      nonsignificant reduction of 41 percent in the number of partial seizures (95
      percent confidence interval, -124 to 84 percent) and a significant 67 percent
      reduction in the number of seizures with generalization (95 percent confidence
      interval, 20 to 86 percent). Most of the difference in the number of partial
      seizures was attributable to a few patients who had many seizures during follow
      up. The proportions of patients who had partial seizures during follow-up were
      similar in the two groups (19 of 57 in the albendazole group and 16 of 59 in the
      placebo group), but the patients in the placebo group had a greater tendency to
      have seizures with generalization (22 of 59, vs. 13 of 57 in the albendazole
      group; risk ratio, 1.63; 95 percent confidence interval, 0.91 to 2.92). More of
      the intracranial cystic lesions resolved in the albendazole group than in the
      placebo group. With the sole exception of abdominal pain, side effects did not
      differ significantly between the two groups. CONCLUSIONS: In patients with
      seizures due to viable parenchymal cysts, antiparasitic therapy decreases the
      burden of parasites and is safe and effective, at least in reducing the number of
      seizures with generalization.

PMID- 14724305
TI  - Clinical practice. Obsessive-compulsive disorder.

PMID- 14724306
TI  - Images in clinical medicine. Neurocysticercosis.

PMID- 14724307
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 2-2004. A 32-year-old man with pain and swelling of the jaw.

PMID- 14724308
TI  - Antiplatelet therapy for ischemic heart disease.

PMID- 14724309
TI  - Neurocysticercosis--is the elimination of parasites beneficial?

PMID- 14724310
TI  - Medical malpractice.

PMID- 14724311
TI  - Cross-reactivity and sulfonamide antibiotics.

PMID- 14724312
TI  - Long-term follow-up of asthma.

PMID- 14724313
TI  - Racial, ethnic, and geographic disparities in rates of knee arthroplasty.

PMID- 14724314
TI  - Autoantibodies before the clinical onset of systemic lupus erythematosus.

PMID- 14724315
TI  - Combined estrogen-progestin oral contraceptives.

PMID- 14724316
TI  - Fundus functionality and ghrelin concentrations after bariatric surgery.

PMID- 14724318
TI  - Cysticercosis in Peace Corps volunteers in Madagascar.

PMID- 14724317
TI  - Rituximab therapy for the type B syndrome of severe insulin resistance.

PMID- 14724319
TI  - Images in clinical medicine. Intussusception.

PMID- 14724321
TI  - Proteomic characterization of protein phosphatase complexes of the mammalian
      nucleus.
AB  - Our knowledge of the serine/threonine protein phosphatases of the mammalian
      nucleus is limited compared with their cytosolic counterparts. Microcystin
      Sepharose chromatography and mass spectrometry were utilized to affinity purify
      and identify protein phosphatase-associated proteins from isolated rat liver
      nuclei. Far Western analysis with labeled protein phosphatase 1 (PP1) showed that
      many more PP1 binding proteins exist in the nucleus than were previously
      demonstrated. Mass spectrometry confirmed the presence in the nucleus of the
      mammalian PP1 isoforms alpha1, alpha2, beta, and gamma1, plus the Aalpha and
      several of the B and B' subunits that are complexed to PP2A. Other proteins
      enriched on the microcystin matrix include the spliceosomal proteins known as the
      U2 snRNPs SAP145 and SAP155 and the U5 snRNPs p116 and p200, myosin heavy chain,
      and a nuclear PP1 myosin-targeting subunit related to M110. The putative RNA
      binding protein ZAP was also established as a nuclear PP1 binding protein using
      the criteria of co-purification with PP1 on microcystin-Sepharose, co
      immunoprecipation, binding PP1 in an overlay assay, and presence of a putative
      PP1 binding site (KKRVRWAD). These results further support a key role for protein
      phosphatases in several nuclear functions, including the regulation of pre-mRNA
      splicing.

PMID- 14724320
TI  - TopNet: a tool for comparing biological sub-networks, correlating protein
      properties with topological statistics.
AB  - Biological networks are a topic of great current interest, particularly with the
      publication of a number of large genome-wide interaction datasets. They are
      globally characterized by a variety of graph-theoretic statistics, such as the
      degree distribution, clustering coefficient, characteristic path length and
      diameter. Moreover, real protein networks are quite complex and can often be
      divided into many sub-networks through systematic selection of different nodes
      and edges. For instance, proteins can be sub-divided by expression level, length,
      amino-acid composition, solubility, secondary structure and function. A
      challenging research question is to compare the topologies of sub- networks,
      looking for global differences associated with different types of proteins.
      TopNet is an automated web tool designed to address this question, calculating
      and comparing topological characteristics for different sub-networks derived from
      any given protein network. It provides reasonable solutions to the calculation of
      network statistics for sub-networks embedded within a larger network and gives
      simplified views of a sub-network of interest, allowing one to navigate through
      it. After constructing TopNet, we applied it to the interaction networks and
      protein classes currently available for yeast. We were able to find a number of
      potential biological correlations. In particular, we found that soluble proteins
      had more interactions than membrane proteins. Moreover, amongst soluble proteins,
      those that were highly expressed, had many polar amino acids, and had many alpha
      helices, tended to have the most interaction partners. Interestingly, TopNet also
      turned up some systematic biases in the current yeast interaction network: on
      average, proteins with a known functional classification had many more
      interaction partners than those without. This phenomenon may reflect the
      incompleteness of the experimentally determined yeast interaction network.

PMID- 14724322
TI  - Vintage gerontology. Cell biologist Judith Campisi's lab has fermented new
      insights into cancer and the biology of aging.

PMID- 14724323
TI  - Skeleton key. Lipid-processing enzyme weakens bones.

PMID- 14724324
TI  - Beta amyloid's accomplice? Molecular hit man might help Alzheimer's protein take
      out brain's white matter.

PMID- 14724325
TI  - Glycation stimulates amyloid formation.
AB  - Amyloidosis comprises a group of systemic and localized diseases with varied
      clinical presentations. In these diseases, amyloid forms when proteins with a
      largely alpha-helical structure lose their original conformation and are
      converted into a predominantly beta-sheet form, thereby increasing their
      propensity to form highly insoluble and fibrillar aggregates. Most soluble
      amyloid precursor proteins have substantial beta-pleated sheet secondary
      structure, and extensive beta-pleated sheet structure occurs in all of the
      deposited fibrils. The aberrant deposition of proteins as cellular inclusions or
      plaques in the form of amyloid fibrils is a characteristic hallmark of all
      amyloid diseases (or amyloidoses) and of the so-called conformational diseases.
      Environmental and genetic factors are known to be involved, but the mechanism by
      which this process happens still is poorly understood. Here we report a new
      finding from the Dutch group of Gebbink and colleagues, which points to the
      posttranslational process of glycation as a key mechanism in the formation of
      amyloid. These researchers showed that glycation causes albumin, a globular
      protein with a largely alpha-helical structure, to adopt a beta-pleated sheet
      structure and the quaternary structural element known as the cross-beta
      conformation. These are features commonly shared by all amyloids. This research
      is the first to show glycation as a predisposing factor for amyloidosis.

PMID- 14724326
TI  - Review of recent guidelines for antiretroviral treatment of HIV-infected
      children.

PMID- 14724327
TI  - Antiretroviral adherence interventions: a review of current literature and
      ongoing studies.
AB  - Adherence has proven to be Achilles' heel of antiretroviral therapy. To achieve
      the nearly perfect adherence apparently necessary for optimal effects,
      individuals often require assistance. In this review, we examine antiretroviral
      therapy adherence intervention studies and reviews published through January 2003
      as well as abstracts of ongoing National Institutes of Health-funded research
      projects aimed at enhancing antiretroviral therapy adherence. The 21 published
      studies we located utilized 4 intervention strategies: cognitive-behavioral,
      behavioral, directly observed therapy, and affective. Most of these were pilot or
      feasibility studies. However, the 4 randomized controlled trials conducted with
      adequate methologic rigor suggest some promising yet preliminary effects of a
      pharmacist-led individualized intervention, a cognitive-behavioral educational
      intervention based on self-efficacy theory, and cue-dose training when combined
      with monetary reinforcement. The 39 ongoing federally funded studies offer
      superior methodologic sophistication and include some innovative strategies, such
      as the use of handheld devices, two-way pagers, and alarmed medication vials,
      along with enhancement of social and emotional support.

PMID- 14724328
TI  - Perinatal HIV: special considerations.
AB  - The percentage of AIDS cases among women--particularly women of color--in the
      United States is increasing yearly. Despite this increase, there has been a
      relatively steady decline in the number of AIDS cases occurring perinatally.
      Regardless of the reasons HIV-infected couples choose to become pregnant, studies
      indicate that providing support, such as contraceptive counseling and assisted
      reproduction techniques, can improve the health outcome in the face of HIV
      related challenges. Issues specific to antiretroviral therapy, including viral
      resistance, pregnancy outcomes, and adverse fetal effects, complicate the
      treatment of perinatal HIV. Postpartum case is yet another area that requires
      special consideration when supporting HIV-infected parents and children. The
      growing body of data on pregnancy and HIV may indicate a rising commitment to
      research of and support for the unique challenges HIV-infected families face.
      This article was adapted from an IAS-USA interactive case-based program, Cases on
      the Web, in November 2003.

PMID- 14724329
TI  - Drug resistance mutations in HIV-1.
AB  - The International AIDS Society-USA (IAS-USA) Drug Resistance Mutations Group is a
      volunteer panel of experts that meets regularly to review and interpret new data
      on HIV-1 resistance. The focus of the group is to identify mutations associated
      with clinical resistance to HIV-1. These mutations have been identified by 1 or
      more of the following criteria: (1) in vitro passage experiments or validation of
      contribution to resistance by using site-directed mutagenesis; (2) susceptibility
      testing of laboratory or clinical isolates; (3) genetic sequencing of viruses
      from patients in whom the drug is failing; (4) correlation studies between
      genotype at baseline and virologic response in patients exposed to the drug.
      Drugs that have been approved by the US Food and Drug Administration (FDA) or
      available through expanded access protocols are included.

PMID- 14724330
TI  - Early influenza in Europe and SARS escaping from high security laboratories!

PMID- 14724331
TI  - SARS: retrospective cohort study among German guests of the Hotel 'M', Hong Kong.
AB  - Hong Kong played a pivotal role in the international spread of the Severe Acute
      Respiratory Syndrome (SARS): a doctor who spent the night of 21-22 February 2003
      at Hotel 'M' was identified as the index case for four national and international
      clusters of SARS. In parallel to the international collaborative study led by WHO
      and United States, a retrospective study on the cohort of German persons staying
      at Hotel 'M' was conducted. The inclusion criteria covered a period from 21
      February to 3 March 2003 to allow the detection of cases possibly due to
      environmental contamination. In the twenty-one German guests traced as having
      stayed at Hotel "M" during this period, one case of laboratory confirmed SARS was
      found. The case history suggests that close vicinity to the index patient may
      have played a role in transmission. In line with findings of environmental
      investigations in the hotel, environmental contamination should be considered as
      a possible source of infection.

PMID- 14724332
TI  - Heterogeneous influenza activity across Europe during the winter of 2002-2003.
AB  - Influenza activity varied across Europe during the 2002-2003 season both in terms
      of the intensity of clinical activity and the circulating virus types/subtypes.
      Influenza B was generally predominant in the 'western' parts of Europe (Portugal,
      Spain, the United Kingdom and Ireland) and influenza A (H3N2) in the 'central'
      and 'eastern' areas (Germany, Italy, Denmark, Switzerland, Poland, Slovenia, the
      Slovak Republic, the Netherlands). A number of countries experienced mixed
      seasons, first experiencing activity associated with influenza B and then with
      influenza A (Belgium, France and Spain). Generally, countries where influenza B
      was predominant had low (compared to historical data) levels of intensity (a mild
      season) and longer periods of influenza activity compared to countries where
      influenza A (H3N2) was predominant. A number of countries, all where influenza A
      (H3N2) was predominant, reported high levels of intensity compared to historical
      data: the Czech Republic, Denmark, Germany and Poland. In the six countries where
      age-specific incidence rates were available, the highest rates were observed
      among those aged 0-14 years. The influenza virus strains circulating in Europe
      had a good match with the virus strains in the influenza vaccine. A small number
      of isolates (A/Fujian/411/2002 (H3N2)-like) were reported at the end of the
      season that had a reduced reactivity to anti-sera of the vaccine strain. The
      composition of the 2003-2004 influenza vaccine is the same as during the 2002
      2003 season.

PMID- 14724333
TI  - The use of near patient tests in influenza surveillance: Swiss experience and
      EISS recommendations.
AB  - Surveillance requires time for analysis and for the communication to physicians.
      In order to reduce this delay, a new surveillance system based on the use of a
      near patient test (NPT) has been evaluated. The high specificity of NPT together
      with the rapidity in obtaining the results, make these tests attractive for
      surveillance of influenza epidemic in community practice. Such surveillance has
      been used in several countries including Switzerland. Four different seasons -
      between 1999 and 2003 - of this type of surveillance experienced in Switzerland
      have been analysed. The heterogeneity in terms of intensity and type of strains
      detected during these four epidemics seasons allowed an efficient evaluation. The
      average gain of time with NPT compared to cell culture was nine days.
      Furthermore, training of participants appeared to be essential to assure the
      quality of the surveillance system. A statement on the use of NPTs for influenza
      surveillance has finally been endorsed by EISS members. Included are
      recommendations that the network should use the NPTs data, which provides
      additional information to the classical surveillance systems, as an "early
      warning" system of a change in influenza activity.

PMID- 14724334
TI  - Asian microcirculation. Proceedings of the Fifth Asian Congress for
      Microcirculation and a related meeting. February 20-22, 2003. Manila,
      Philippines. March 10-14, 2003. Bangkok, Thailand.

PMID- 14724335
TI  - Rheology of the microcirculation.
AB  - The main function of the microvasculature is the controlled exchange of materials
      with surrounding tissues. This necessitates a large vessel surface established by
      a high number of vessels with small diameters and thus an inherently high
      individual resistance to flow. The hydrodynamic resistance of a microvascular
      network with given angioarchitecture depends on the apparent viscosity of blood
      flowing in the microvessels. Apparent viscosity declines with decreasing diameter
      (the Fahraeus-Lindqvist effect) and is minimal at diameters of about 5-7
      micrometers due to the optimal alignment of red cells with the flow. In vivo, a
      number of additional phenomena influence blood rheology and network hemodynamics.
      The distribution of blood flow and red cell flux within networks is influenced by
      the mechanics of red cell motion at individual diverging bifurcations (phase
      separation effect). Furthermore, recent studies have revealed the presence of a
      thick endothelial surface layer ( approximately 0.5 micrometers) on the luminal
      surface of microvessels which is attached to the endothelial glycocalyx. This
      layer modulates flow resistance and may be relevant for a number of other
      processes such as inflammatory responses and blood coagulation. Information on
      microvascular rheology can be used to develop mathematical models of network
      hemodynamics and vascular adaptation to the local environment (angioadaptation),
      to investigate the complex interrelated mechanisms which establish and maintain
      functionally adequate microvascular networks.

PMID- 14724336
TI  - Cerebral angiogenesis induced by growth factors: intravital microscopic studies
      using models.
AB  - Pharmacological induction of angiogenesis is a new treatment of cerebrovascular
      insufficiency without surgical treatment. It is an urgent task to investigate the
      dynamic process of angiogenesis and of the microvascular perfusion of the
      cerebral neoplastic tissue in vivo. The present study is concerned with
      microcirculatory aspects of cerebral neocapillaries in vivo. A novel model of
      cerebral angiogenesis was developed by inducing cerebral neocapillaries in mice
      using growth factors such as basic fibroblast growth factor (bFGF) and platelet
      derived growth factor (PDGF). By a direct observation of the neocapillary
      microcirculation under a fluorescence videomicroscope, the neocapillary density,
      diameter and red cell velocity were measured to evaluate the development and
      remodeling of the neocapillaries with the number of days after incubation. The
      neocapillary response to topically applied acetylcholine (ACh) was examined by
      measuring changes in the diameter and red cell velocity. It was shown that PDGF
      induced neocapillaries was dilated in response to ACh on day 28 after incubation,
      while bFGF-induced neocapillaries was not. Furthermore, the neocapillary
      pericytes were observed using confocal laser microscopy, based on the
      fluorescence immunohistochemical images of the neoplastic tissue. Several
      pericytes, stained with anti-NG_2, appeared in the neocapillaries. It was
      suggested that these pericytes might be recruited in the neocapillaries to
      regulate blood flow without vascular smooth muscle.

PMID- 14724337
TI  - Microcirculation: target therapy in cardiovascular diseases - a clinical
      perspective.
AB  - Microcirculation conduit, distribution, exchange and reception vessels usually
      retain a demand-dependent vascular-tissue match as well as a nutrient friendly
      capillary-matrix tissue match. Various stimuli can initiate a vascular-capillary
      matrix-tissue mismatch. Counter-regulatory mechanisms result in hyperplasia or
      apoptosis. Microvascular disease (MVD) as a consequence or outcome of supply
      demand mismatch has clinical therapeutic and prognostic implications in the
      hypertensive syndrome and coronary artery disease (CAD) cases. Recognition of the
      role of apoptosis and MVD may initiate a paradigm shift in clinical practice.
      Digitalis and other anti-hypertensive agents have anti-apoptotic action and MVD
      blunting effects that can control LVH development to reduce congestive heart
      failure (CHF) progression.

PMID- 14724338
TI  - Regulatory mechanisms of hepatic microcirculation.
AB  - Hepatic microvasculature receives blood from two types of afferent vessels: the
      terminal portal venule (TPVn) and the terminal hepatic arteriole (THAo). The
      TPVns directly connect with the capillary bed in the liver parenchyma, which is
      referred to as sinusoids. Hepatic arterial blood pours into the hepatic sinusoids
      not only indirectly via the anastomosis between the THAo and the portal venule
      (PVn), but also directly through the THAo or the capillaries derived from the
      arterial capillary network around the bile duct. From a regulatory point of view,
      the hepatic arterial system is considered to be supplementary, but hepatic
      arterial flow is essential for supplying oxygen to sinusoidal blood flow as well
      as to the bile ducts, portal venules and nerves in the portal tract. The main
      regulators of hepatic sinusoidal blood flow are present in the portal venous
      system. By intravital and scanning electron microscopy, it is evident that a
      potent vasoconstrictor endothelin (ET)-1 causes a contraction of the SEF via the
      ET_B receptors, as well as a significant contraction of the PVn and TPVn,
      resulting in an increase in sinusoidal and pre-sinusoidal microvascular
      resistance. This phenomenon implies that the TPVn, particularly the transitional
      part to the sinusoid, would provide an essential regulatory site for hepatic
      sinusoidal blood flow as an inlet sphincter-like function. The endothelial cell
      linings along the hepatic sinusoids are characterized by the presence of a large
      number of sieve plate-like pores, 100 nm in diameter, i.e. the sinusoidal
      endothelial fenestrae (SEF). The SEF are dynamic structures, forming the racemose
      invaginations of the endothelial plasma membrane across the endothelium, and
      regulating not only the permeability of hepatic sinusoids, but also the
      sinusoidal blood flow by the Ca++ -actomyosin-mediated contraction and dilatation
      of the SEF. Our recent immunoelectron microscopic and Western blot studies have
      revealed that caveolin-1, i.e. the principal structural protein of caveolae, and
      endothelial nitric oxide synthase (eNOS) co-exist in the plasma membrane of the
      SEF, implying that the SEF may correspond to a permanent (stationary) type of
      fused and interconnected caveolae, thus contributing to the local control of
      hepatic sinusoidal blood flow by the regulation of NO synthesis.

PMID- 14724339
TI  - A hemodynamically mediated mechanism of renal disease progression in severe
      glomerulonephritides or nephrosis.
AB  - Glomerular endothelial cell (GEC) dysfunction due to oxidative stress and
      enhanced proinflammatory cytokines plays an important role in inducing
      proteinuria and procoagulant activity, namely blood hypercoagulability,
      hyperviscosity and local intravascular coagulation and altered hemorheology in
      NS. A dysfunctioning GEC releases fewer endothelium-dependent vasodilators but
      produces more vasoconstrictors. Severe intrarenal hemodynamic alteration
      associated with hemodynamic maladjustment with preferential constriction at the
      efferent arteriole has been uniquely implicated in severe GN and NS-FSGS. Such a
      constriction exerts three significant hemodynamic impacts. Proximal to the
      efferent arteriolar constriction, it induces (i) an overestimated GFR due to
      hyperfiltration and (ii) an elevated intraglomerular hydrostatic pressure. Distal
      to the efferent arteriolar constriction, it (iii) exaggeratedly reduces PTCF
      which correlates with the TIF.

PMID- 14724340
TI  - Micro-vascular medicine and proteomics.
AB  - A new technique is sweeping the world, and changing the course of human work and
      life. It is impacting upon models, methods and the development of medical
      research. In the development of this new technique, a huge quantity of
      experimental research and clinical practice has proved that many human diseases
      have a close relationship to pathological changes that take place in the
      microvascular system. It has been proven that the microvascular system is the
      target for studying disease development and the treatment of disease. Many
      studies have shown that successful pathogenesis and pathological research must be
      aimed at understanding the key proteins in cells, organs and systems, as well as
      investigating their interaction, and finding out how these proteins change under
      disease conditions. This paper reviews the current status of microvascular
      medicine and proteomics.

PMID- 14724341
TI  - Asian traditional medicine (ATM) based on in vivo microcirculation evidence.
AB  - Asian traditional medicine (ATM) (herbal medicine, acupuncture or moxibution) has
      gained some popularity among communities in Asia, but there are still few
      evidences to prove the effectiveness of such therapeutic measures. A symposium
      was held with aim at the effectiveness of Asian traditional therapies in views of
      in vivo microcirculation. This report is concerned with the symposium, including
      Asian activities for ATM.

PMID- 14724342
TI  - Angiotherapeutics from natural products: from bench to clinics?
AB  - Angiogenesis offers an enormous potentials for therapeutic intervention of many
      disorders afflicting mankind at present. With the identification of the major
      molecular players involved in the sequence of events leading to the formation of
      new blood vessels from pre-existing capillaries, inhibition or induction of the
      process may now be regulated. Bioactive compounds from natural sources may be
      used as regulatory agents. Inhibition of angiogenesis can control diseases
      characterized with excessive blood vessel growth like cancer, arthritis,
      psoriasis and diabetes retinopathy. Stimulation of angiogenesis would be
      favorable in the treatment of ischemic disorders and tissue engineering. An
      increasing number of bioactive compounds from natural sources and whose chemical
      structures have already been elucidated are reported as either potential
      inhibitors or inducers of angiogenesis. Drug development from natural products is
      a fast-emerging field that needs to be supported to provide people with more
      readily available and affordable healthcare.

PMID- 14724343
TI  - Treatment of glomerular endothelial dysfunction in steroid-resistant nephrosis
      with Ganoderma lucidum, vitamins C, E and vasodilators.
AB  - Glomerular endothelial dysfunction is believed to be responsible for the
      proteinuria and nephronal damage, namely tubulointerstitial fibrosis and
      glomerulosclerosis, observed in severe nephrosis such as focal segmental
      glomerulosclerosis. A dysfunctioning glomerular endothelium is likely to be
      induced by oxidative stress and oxidized LDL as well as altered immunocirculatory
      balance with a defective anti-inflammatory pathway. A defective release of
      vasodilator inconjunction with enhanced production of angiotensin II induces
      hemodynamic maladjustment by preferential constriction at the efferent arteriole.
      Such a hemodynamic maladjustment exerts two significant hemodynamic impacts.
      Close to the efferent constriction, it induces intraglomerular hypertension and
      glomerulosclerosis. Far from the efferent constriction, it reduces peritubular
      capillary flow, which eventually leads to tubulointerstitial fibrosis. Treatment
      with a vasodilator improves the hemodynamic maladjustment but does not completely
      suppress proteinuria. A successful suppression of proteinuria is accomplished by
      using Ganoderma lucidum and vitamins C and E. The beneficial effect of Ganoderma
      lucidum appears to be multifactorial, including the modulation of
      immunocirculatory balance, antilipid, vasodilator, antiplatelet and improved
      hemorheology. Together with vitamins C and E, this helps to neutralize oxidative
      stress and suppress the toxic effect to the glomerular endothelial function.

PMID- 14724345
TI  - Possible immunomodulatory actions of Carica papaya seed extract.
AB  - Carica papaya seed extract is currently being marketed as a nutritional
      supplement with purported ability "to rejuvenate the body condition and to
      increase energy". The product claims to improve immunity against common infection
      and body functioning. The present study was initiated to analyze the chemical
      constituents of the Carica Seed Extract and determine the potential
      immunomodulatory properties of the different bioactive fractions. These
      immunomodulatory activities of crude Carica Seed Extract and its bioactive
      fractions were examined in vitro using lymphocyte proliferation assays and
      complement-mediated hemolytic assay. Three major observations were made in this
      study: (1) the crude Carica Seed Extract and two other bioactive fractions
      significantly enhanced the phytohemagglutinin responsiveness of lymphocytes; (2)
      none of the Carica Seed Extract (at the concentrations used in this study) was
      able to protect the lymphocytes from the toxic effects of chromium; and (3) some
      of the bioactive fractions of Carica Seed Extract were able to significantly
      inhibit the classical complement-mediated hemolytic pathway. These findings
      provide evidence for immunostimulatory and anti-inflammatory actions of Carica
      Seed Extract. No single compound is likely responsible for these activities.
      Further purification, isolation and characterization of the active components are
      needed.

PMID- 14724344
TI  - The mechanism of Polydatin in shock treatment.
AB  - Polydatin is extracted from a traditional Chinese herbal medicine, Polygonum
      cuspidatum, and has a special effect in shock treatment. The aim of this study is
      to explain the cellular and molecular basis of Polydatin in shock treatment. The
      fluorescent probe techniques, patch clamp method, and cellular flow chamber were
      used to test intracellular variables of vascular smooth muscle cells (VSMC),
      myocardial cells (MC), endothelial cells (EC), and white blood cell (WBC). It was
      shown that Polydatin could inhibit ICAM-1 expression in EC stimulated by
      lipopolysaccharide (LPS), attenuate WBC-EC adhesion, increase [Ca2+]i in MC with
      enhancement of MC contraction extent, activate KATP channels of VSMC, and
      decrease pHi value and [Ca2+]i of VSMC in shock. The study suggests that
      Polydatin has multiple effects on VSMC, MC, WBC and EC, which are related to the
      enhancement of heart function and improvement of microcirculatory perfusion in
      shock.

PMID- 14724346
TI  - Effects of extract of Ginkgo biloba on spasms of the basilar artery and cerebral
      microcirculatory perfusion in rats with subarachnoid hemorrhage.
AB  - This study was aimed at investigating the effects of extract of Ginkgo biloba
      (EGb) on cerebral vasospasm and microcirculatory perfusion after subarachnoid
      hemorrhage (SAH). An endovascular piercing method was used to induce Wistar rat
      SAH models, and animals were divided into sham-operated, vehicle controls, and
      EGb-treated groups. EGb was injected intraperitoneally 30 minutes before
      operation and was repeated every 6 hours, with a single dose of 15 mg/kg bw.
      Diameters of basilar arteries before and after operation were measured.
      Microcirculatory blood perfusion of parietal lobe cortex was detected using a
      laser Doppler flow-meter probe within 24 hours. Endothelin-1 levels in both
      plasma and brain tissue were detected at different time points. The results
      showed that SAH caused an immediate drop in microcirculatory blood flow in
      vehicle controls, which persisted for 24 hours. Endothelin-1 levels in both
      plasma and brain tissue increased after SAH. EGb partly reversed spasms of the
      basilar artery and antagonized a drop in microcirculatory blood flow. EGb also
      prevented an increase in endothelin-1 both in plasma and in brain tissue. In
      conclusion, EGb, by antagonizing the overproduction of endo- thelin-1, partly
      reverses cerebral vasospasm and improves microcirculation, and thus relieves
      secondary ischemic brain injury after experimental SAH.

PMID- 14724347
TI  - Effects of Aloe vera on leukocyte adhesion and TNF-alpha and IL-6 levels in burn
      wounded rats.
AB  - The effects of Aloe vera on microcirculation and levels of TNF-alpha and IL-6
      were investigated in rats after inducing burn. Seventy-two male Wistar Furth rats
      were equally divided into four groups as follow: controls (CON), untreated burn
      wound rats (BURN), normal saline-treated burn-wound rats (BURN-NSS) and Aloe vera
      treated burn-wound rats (BURN-ALOE). The animals in each group were equally
      subdivided into three subgroups for the study on day 3, 7 and 14 post-burn.
      Dorsal skinfold chamber preparation and intravital fluorescence microscopic
      technique were performed to examine leukocyte adhesion on postcapillary venules.
      ELISA techniques were performed to examine serum TNF-alpha and IL-6 levels. It
      was found that the amount of leukocyte adhesion was significantly reduced in the
      BURN-ALOE group compared to rats in the BURN group on day 14. Levels of TNF-alpha
      and IL-6 were also decreased significantly compared to BURN at all three
      monitored time points. Aloe vera could inhibit the inflammatory process following
      burn injury, as characterized by the reduction of leukocyte adhesion, as well as
      those pro-inflammatory cytokines.

PMID- 14724348
TI  - Tonkin herbal drug: a multidisciplinary approach to development.
AB  - Ipomoea muricata (L.) Jacq, locally known as 'Tonkin', has been used for
      generations by the Dominicans in the Philippines for medicinal purposes. The
      seeds, stems and leaves are said to be effective in treating several types of
      skin ailments such as chronic and gangrenous wounds, cuts and blisters due to
      burns. Scientific investigations to rationalize the reported medicinal uses of
      the plant were carried out at University of Santo Tomas. Botanists at the
      University did the identification and studied the cultivation and propagation of
      the plant. Pharmacists and chemists worked closely together on the 'Tonkin'
      seeds. The seeds were found to have both analgesic and antiseptic properties.
      Chemists identified indolizidine alkaloids in the seeds, to which the analgesic
      properties have been attributed. Antimicrobial and antifungal compounds were also
      identified. Different formulations of the crude drug have been made, namely, an
      ointment for the treatment of skin ailments, glycerol preparation for the
      treatment of pharyngitis and an otic preparation for the treatment of otitis
      externa. Limited clinical trials of these formulations were carried out in
      collaboration with the medical doctors. The clinical trial studies were supported
      by in vitro studies carried out by microbiologists. Basic research on this plant
      material is still continuing. Efforts are now underway for the commercial
      production of the Tonkin ointment.

PMID- 14724349
TI  - The gastroprotective effect of tannins extracted from duhat (Syzygium cumini
      Skeels) bark on HCl/ethanol induced gastric mucosal injury in Sprague-Dawley
      rats.
AB  - The gastroprotective effect of quantified tannins (13.4%) from Syzygium cumini
      was determined. Gastric mucosal damage was induced in sixty eight rats by oral
      gavage administration of HCl/ethanol solution. For macroscopic and microscopic
      studies, 30 rats were divided into three groups consisting of a negative control,
      an Omeprazole group and a Tannins group. There was no significant difference in
      the number, size and surface area of macroscopic lesions between the three
      groups. Microscopic examination using Best's Ulcer Staging Index showed that
      Tannins had a very significant decrease in gastric mucosal damage with p<0.01.
      Average lymphocyte populations in the three groups showed no significant
      difference, although both the Tannins and Omeprazole group had fewer lymphocytes.
      Thirty-eight rats were studied for the amount of free radicals present after
      induction of gastric damage. A dose which consisted of 20.0 g tannins/kg rat
      weight showed significantly lower stomach free radical concentrations. These
      findings suggest that tannins extracted from S. cumini have gastroprotective and
      anti-ulcerogenic effects.

PMID- 14724350
TI  - The oxygen-binding capacity of human erythrocyte in iota-carrageenan solution and
      conventional plasma expanders.
AB  - The oxygen binding capacity of human erythrocytes in selected solutions was
      studied in vitro. Three treatment groups were used in the study: 0.08% iota
      carrageenan solution, dextran 70, and normal saline solution (NSS). The different
      treatment groups were oxygenated. The percent oxygen saturation and oxygen
      partial pressure were determined by blood gas analysis, and oxyhemoglobin
      absorbance was measured using spectrophotometry. Analysis of variance (ANOVA) and
      Tukey's HSD Test were used to analyze the data. There were significant
      differences (p<0.05) observed in the percent oxygen saturations and oxygen
      partial pressures among the three treatment groups, with NSS having the highest
      values (97.65+/-0.385% and 160.18+/-152.567 mmHg, respectively) followed by
      dextran 70 (95.38+/-1.093% and 142.68+/-73.967 mmHg, respectively) then iota
      carrageenan (89.42+/-4.327% and 94.02+/-17.912 mmHg, respectively). However,
      there were no significant differences observed in the absorbance values of
      oxyhemoglobin among the three set-ups. It was concluded that the oxygen binding
      capacity of erythrocytes in iota-carrageenan solution is significantly lower than
      that in dextran 70 and NSS.

PMID- 14724351
TI  - Genistein replacement therapy for vasodilation disorder in bilateral
      ovariectomized rats.
AB  - The objective of this study is to examine the effects of genistein on endothelial
      dysfunction in bilateral ovariectomized rats. Female Wistar rats were subjected
      to a bilateral ovariectomy (OVX rat). The animals were divided into three groups:
      sham treated with vehicle (DMSO 100 microliters/day, Shamveh), OVX treated with
      vehicle (DMSO 100 microliters/day, OVXveh), and OVX treated with genistein (0.25
      mg/kg BW/day, OVXgen). Mean arterial pressure (MAP), heart rate (HR), body weight
      (BW), uterine weight and plasma E2 were monitored at 4-week after the treatment.
      We investigated the endothelium-dependent and -independent vasorelaxation by
      using acetylcholine (Ach 10(-6) M) and sodium nitroprusside (SNP 10(-7) M),
      respectively. The experimental results indicated that the uterine weights of all
      OVX rats were significantly decreased as compared to the sham groups (OVXveh =
      0.007+/-0.004 g, OVXgen =0.003+/-0.001 g, Shamveh =0.017+/-0.001 g). MAP of
      OVXveh group was significantly increased compared to the Sham group
      (OVXveh=139.99+/-7.50 mmHg, Shamveh =118.10+/-19.33 mmHg, p<0.05). No significant
      increase in MAP was observed in OVXgen (OVXgen =123.33+/-8.61 mmHg; p<0.05). HR
      showed no significant difference among those groups. The present study of
      vasodilator responses demonstrated only the significant decrease in endothelium
      dependent, not for endothelium-independence, in OVX rats, while the treatment of
      genistein could significantly attenuate this abnormality (OVXveh =3.03+/-3.99%,
      Shamveh =45.46+/-3.59%, OVXgen =33.52+/-3.25% in % change of vessel diameter).
      The present findings suggest that genistein could be used as a therapeutic agent
      for menopausal vascular complications.

PMID- 14724352
TI  - Carrageenan plasma expander: effect on mesenteric ischemia-reperfusion injury in
      the rat.
AB  - The effect of carrageenan against ischemia-reperfusion injury was investigated.
      Rats were grouped into four, subjected to 10 min of ischemia and reperfusion in
      their mesenteric venules and 30% of their blood volume was replaced with either
      normal saline solution, dextran 70 in 5% dextrose, or iota-carrageenan solution,
      while the fourth group remained untreated. Parameters such as venule diameter,
      red blood cell velocity, leukocyte rolling and adhesion, were then observed by
      video. Findings reveal that carrageenan infusion has the tendency to attenuate
      leukocyte rolling and adhesion, increase venule diameter and regain erythrocyte
      velocity after ischemia. The data suggest that the effects of carrageenan were
      comparable to that of either of the more commercially used plasma expanders,
      dextran 70 or normal saline solution. Overall, however, these did not differ
      significantly from the untreated rats.

PMID- 14724353
TI  - Early pathophysiological changes in cerebral vessels predisposing to stroke.
AB  - We studied the early pathophysiological response of lenticulostriate arterioles
      in rats in three models of human conditions associated with stroke: (a) chronic
      angiotensin II-hypertension; (b) chronic nicotine administration; (c) oxidative
      endothelial injury. In all three models, quantitative patch clamp analysis of
      freshly isolated vascular smooth muscle cells from lenticulostriate arterioles
      and posterior cerebral arteries showed significant increases in activity of
      functional L-type calcium channels that were due to an increase in open channel
      probability, with no change in other biophysical properties or in channel
      expression. In addition, all three models showed evidence of endothelial
      dysfunction, but of a different nature in the three. With chronic angiotensin II
      hypertension, but not in the other two models, endothelial nitric oxide synthase
      (eNOS) was dysfunctional, was mislocalized away from its normal abluminal
      location, and was accumulated in peri-nuclear Golgi. By contrast, the other two
      models showed no mislocalization of eNOS, but instead showed evidence of
      oxidative stress in endothelium, with up-regulation of superoxide dismutase and
      hexose kinase. All three models showed significant up-regulation of expression of
      proliferative cell nuclear antigen (PCNA) (PCNA index, 70-80%) in arterioles in
      situ, which is associated with increased activation of the nuclear transcription
      factor, phospho-cAMP response element binding protein (phospho-CREB). In
      addition, calmodulin-dependent protein (CaM) kinase II was activated, in concert
      with the activation of L-type calcium channels. Furthermore, blockers of either L
      type calcium channels (amlodipine) or of CaM kinase II (KN-93) completely
      prevented the activation of CREB and the up-regulation of PCNA in arterioles. Our
      findings demonstrate that abnormal regulation of L-type calcium channels is
      directly responsible for abnormal proliferative responses in vascular smooth
      muscle in various forms of cerebral arteriolar injury associated with endothelial
      dysfunction.

PMID- 14724354
TI  - Microvascular disease relevance in the hypertension syndrome.
AB  - Hypertension is not an isolated problem. Co-morbidities of smoking, obesity,
      diabetes and dyslipidemia are all associated with microvascular disease (MVD)
      with abnormal PET scan and endothelial dysfunction. MVD may contribute to left
      ventricular hypertrophy (LVH) via an imbalance between hyperplasia and apoptotic
      signals. Digitalis and other anti-hypertensive agents have anti-apoptotic action
      and MVD blunting effects, respectively. Heart failure progression must then be
      based on the preservation of myocyte integrity. Indeed, altered contractility
      appears to be a consequence of rather than the cause of myocyte deterioration. LV
      systolic dysfunction improvement is already a late strategy. Furthermore, the
      efficacy of anti-hypertension therapy may be limited in restoring LV diastolic
      function. Recognition of the role of apoptosis and MVD may initiate a paradigm
      shift in clinical practice.

PMID- 14724355
TI  - A possible defensive mechanism in the basal region of gastric mucosa and the
      healing of erosions.
AB  - A possible defensive mechanism in the basal region of the gastric mucosa was
      hypothesized in the present study. In vivo microscopy was performed to observe
      the basal region after thermal injury to the back skin of rats. A donor of nitric
      oxide, 3-morpholinosydnonimine hydrochloride (SIN-1), or a serine protease
      inhibitor, camostat mesilate, was administered. Anti-vascular endothelial growth
      factor (VEGF) neutralizing antibody was administered 5 hours after thermal injury
      (anti-VEGF group). Post-capillary venules could be observed in the basal region
      of the gastric mucosa (PV-BGM). The PV-BGM was dilated 5 hours after thermal
      injury, and it was reduced by the administration of SIN-1 or pre-treatment with
      camostat mesilate. In the control group, the erosions did not reach the basal
      region of the gastric mucosa. Most of the erosions healed within 72 hours.
      Delayed healing was observed in the anti-VEGF group. In this group, exudation and
      congestion in the basal region were observed at 24 hours, and ulcer formation was
      observed at 72 hours after thermal injury. It is thus hypothesized that blood
      flow of the PV-BGM increases when superficial mucosal circulation is disturbed.
      The PV-BGM can contribute to defensive mechanisms in the basal region of gastric
      mucosa. The abnormal healing process may disturb the defensive mechanism at the
      base of the gastric mucosa, thereby resulting in ulcer formation.

PMID- 14724356
TI  - The effect of long-term supplementation of vitamin C on pulpal blood flow in
      streptozotocin-induced diabetic rats.
AB  - To examine the effect of vitamin C on blood flow in diabetic dental pulp, the
      animal model of streptozotocin (STZ)-induced diabetic rats (i.v. injection of STZ
      55 mg/kg BW) was used. Male Sprague-Dawley rats weighing 200-250 g were divided
      into 3 groups: non-diabetes (CON), diabetes (STZ), and diabetes supplemented by
      vitamin C (STZ+Vit C). Vitamin C was supplemented by drinking water (1 g/l). At
      12 weeks (wks) and 24 wks after the STZ injection, the laser Doppler flow-meter
      (Model ALF 21, USA) was used to measure pulpal blood flow (PBF) while the animals
      were anesthetized with sodium pentobarbital (50 mg/kg BW). The experimental
      results showed that at 12 and 24 wks after the STZ injection, hyperglycemia
      hypertension and loss of body weight were significantly developed.
      Simultaneously, decreased plasma vitamin C level was demonstrated significantly
      in STZ rats. The reduction of pulpal blood flow (PBF) in the lower incisors was
      observed in STZ rats at both monitored time points. Interestingly, the
      supplementation of vitamin C for 24 wks restored PBF. In conclusion, the present
      study demonstrated that long-term supplementation of vitamin C, a natural
      antioxidant, could markedly prevent the diabetic-induced reduction in PBF.

PMID- 14724357
TI  - The correlation between markers of oxidative stress and risk factors of coronary
      artery disease in Thai patients.
AB  - An imbalance between oxidative damage and antioxidative protection in association
      with the pathophysiology of atherosclerosis has been suggested. The aim of our
      study was to investigate the relationship between plasma lipids, the antioxidant
      system and oxidative damage in Thai patients with stable coronary artery disease
      (CAD). Sixty-one patients (40 males, 21 females), who were angiographically
      defined as having CAD and were clinically stable, participated in this study.
      Thirty-two healthy subjects (20 males, 12 females) served as normal controls. The
      investigation included the measurements of plasma lipid profiles and plasma total
      antioxidative status (TAS) such as plasma vitamin E erythrocyte glutathione (GSH)
      and glutathione peroxidase (GPx), as well as malondialdehyde (MDA) and total
      plasma total protein thiols (P-SH). In patients with CAD, erythrocyte GSH and GPx
      were significantly lower than those found in controls. However plasma TAS and
      vitamin E were not significantly different between groups. Patients with CAD also
      had higher MDA and lower P-SH levels than the controls, which represents the
      oxidative damage products of lipid and proteins. Multiple regression analysis
      revealed negative correlations between GSH and cholesterol, GSH and low density
      lipoprotein (LDL), vitamin E and MDA, as well as P-SH and MDA. This study
      demonstrated the status of oxidative stress in patients with stable CAD. Since
      oxidative stress is the imbalance between the total oxidants and antioxidants in
      the body, any single oxidant/antioxidant parameter may not reflect the overall
      oxidative stress system. Thus, in patients with CAD, diets with various types of
      antioxidants may be more beneficial in increasing antioxidant activity than any
      particular antioxidant supplementation.

PMID- 14724358
TI  - Cerebral endothelial dysfunction in diabetes: intravital microscopic analysis
      using streptozotocin-induced diabetic rats.
AB  - Endothelial function of cerebral microvessel in diabetes was evaluated using
      streptozotocin (STZ)-induced diabetic rats (blood glucose of >/=300 mg/dl). At 36
      weeks after STZ injection, the rats were anesthetized with sodium pentobarbital.
      The cerebral microcirculation in control and STZ groups was directly observed,
      using intravital fluorescence videomicroscopy. To evaluate the endothelial
      function in vivo, the number of leukocytes adhering to postcapillary venules were
      counted, and cerebral arteriolar responses to acetylcholine (ACh) and
      nitroglycerine (NTG) were examined. The results showed that the leukocyte
      adhesion to cerebral postcapillary venular endothelium increased significantly in
      STZ-rats, compared with control rats. The vasodilatory responses of cerebral
      arterioles (20-30 microm) to ACh decreased significantly in STZ-rats, compared
      with control rats (p<0.01), but the responses to NTG did not alter in diabetes.
      These results indicate that the impaired responses should occur on the
      endothelial cell. In conclusion, endothelial dysfunction induced in diabetes are
      characterized by impaired endothelium-dependent vasodilation and increased
      leukocyte adhesion to endothelial cells.

PMID- 14724359
TI  - The effects of nimodipine on regional cerebral blood flow, brain water and
      electrolyte contents in rats with subarachnoid hemorrhage.
AB  - Secondary cerebral ischemic injury is a major cause of mortality and disability
      from subarachnoid hemorrhage (SAH). In this study, the protective effects of
      nimodipine were investigated. Rat SAH models were divided into a sham-operated
      group, a saline-controlled, and a nimodipine-treated group by an endovascular
      piercing method. Nimodipine, 100 microg/kg BW was injected intraperitoneally 30
      minutes before operation and was repeated every 6 hours. Dynamic changes in
      cortical regional cerebral blood flow (rCBF) using a laser Doppler flow-meter
      probe, and somatosensory evoked potentials (SEP) were estimated. Brain water
      content, sodium, potassium and calcium contents at different time points were
      determined. rCBF, latency of SEP, brain water and electrolyte contents did not
      statistically change in sham-operated rats. In saline-controlled rats, rCBF
      decreased immediately after SAH, and stabilized at low levels within 24 hours.
      The latency of SEP delayed gradually after SAH. Brain water and sodium increased,
      while potassium decreased at 6 hours and 24 hours. Brain calcium content
      increased significantly from 1 hour to 24 hours after induction of SAH. Extents
      of alterations of the above parameters caused by SAH in the nimodipine-treated
      group were less than those in the saline-controlled group, statistically. In
      conclusion, nimodipine partly prevents a decrease in cerebral blood supply and
      attenuates secondary cerebral ischemic injury after SAH.

PMID- 14724360
TI  - The effect of cerebral lymphatic blockage on cortex regional cerebral blood flow
      and somatosensory evoked potential.
AB  - Disputes on the significance of cerebral lymphatic drainage pathways under
      physiological and pathophysiological conditions still exist. The purpose of this
      experiment is to investigate the influence of cerebral lymphatic blockage on
      cerebral blood flow and cortex somatosensory evoked potential. Wistar rat
      cerebral lymphatic blockage models were established by removing cervical
      lymphatic nodes after obstructing their input and output tubes. Animals were
      divided randomly into a sham-operated group and a cerebral lymphatic-blockage
      group. Regional cerebral blood flow in different regions of the cortex were
      detected using a laser-Doppler flowmeter probe, and cortex evoked potential was
      detected using an electromyogram and evoked potential instrument before the
      operation, then 1 day, 5 days and 7 days after the operation. Results showed that
      the sham operation had no obvious effect on regional cerebral blood flow and the
      latency of somatosensory evoked potential. From 1 day to 7 days after cerebral
      lymphatic obstruction, regional cerebral blood flow in different cortical regions
      decreased markedly (P<0.01). Latency of somatosensory evoked potential was
      significantly delayed on the 5th and 7th day after blockage of cerebral lymphatic
      drainage (P<0.01). We concluded that cerebral lymphatic drainage may play an
      important role in maintaining the equilibrium of the internal environment of the
      brain, and blockage of this pathway results in cerebral ischemia.

PMID- 14724361
TI  - Analysis of factors influencing the blood levels and activities of tissue-type
      plasminogen activator (t-PA).
AB  - This study aimed to correlate plasmatic tissue-type plasminogen activator (t-PA)
      levels and activity with parameters of artery blood flow and vessel walls, nail
      fold microcirculation, hemorheology, serum glucose, and lipids. Thirty healthy
      volunteers (female/male 12/18) aged 40-60 (average 46) were included in the
      study. In citrate venous blood, the following parameters were determined: carotid
      mean velocity, carotid intimal-medial-thickness (IMT), capillary circulation
      parameters, hemorheology index, serum glucose, and lipids. Analysis of data
      showed that t-PA concentration was positively and significantly correlated with
      total cholesterol, triglycerides, and serum glucose (P<0.05, P<0.05, and P<0.01),
      but t-PA activity showed no correlation with them; among the hemorheology factors
      investigated, t-PA concentration showed the strongest positive correlation with
      both whole blood viscosity and reduced blood viscosity at high and low shear rate
      separately (P<0.01), t-PA activity showed no correlation with any hemorheology
      factors; t-PA concentration showed no correlation with any investigated nail fold
      capillary parameters, whereas t-PA activity was significantly and negatively
      associated with capillary loop number (P<0.05); t-PA concentration and activity
      was not associated with values of carotid maximum intimal-medial-thickness (mIMT)
      and mean velocity or systolic, diastolic blood pressure (P>0.05). But subjects
      with mIMT 1.0 mm showed higher t-PA levels compared with those with mIMT < 1.0 mm
      (P<0.05) and decreased carotid mean velocity (P<0.01). These findings suggest
      that multiple vascular disease risk factors would influence the t-PA level; t-PA
      concentration does not parallelize with t-PA activity.

PMID- 14724362
TI  - Fluorescein angiographically evident diabetic maculopathy.
AB  - Diabetic maculopathy seen in the Philippines, specifically, the associated
      factors, the various lesions seen on fluorescein angiography, and the visual
      acuity associated with these lesions were characterized using 127 patients (254
      eyes) with diabetic retinopathy based on the fluorescein angiography done at the
      Eye Referral Center in 1993. Results showed that 116 (91.34%) patients have
      maculopathy, the majority of which is bilateral (84.25%). Age (p=0.675), sex
      (p=0.357), hypertension (p=0.742), duration of diabetes (p=0.778) and myopia
      (p=0.742) were not significantly associated with maculopathy. However, severity
      of retinopathy (p=0.001) was significantly associated with it. Fluorescein
      angiographic findings are macular staining (83.86%), perifoveal capillary dropout
      or macular ischemia (10.76%), and preretinal traction and membrane (5.38%).
      Microaneurysm (72.65%) is the most common lesion associated with macular
      staining, followed by capillary leakage (4.04%), cystoid macular edema (3.59%),
      perifoveal capillary dropout with microaneurysm (2.24%), and capillary with
      microaneurysm leakage (1.34%). Exudates are associated with microaneurysm,
      perifoveal capillary dropout or a combination of the two. Vision was found to be
      marginally statistically different between the normal and maculopathy group
      (p=0.0505). The worst vision was seen in macular ischemia and preretinal traction
      and membrane, with mean visual acuity of 0.18 and 0.25, respectively. It is
      concluded that severity of retinopathy is the only variable significantly
      associated with maculopathy in this study. Good vision does not necessarily
      indicate a normal macula. Detailed examination and fluorescein angiography should
      be carried out, regardless of duration of diabetes.

PMID- 14724363
TI  - Experimental study on the function of cardiomyocytes.
AB  - This paper aimed at investigating the properties of cultured cardiomyocytes using
      microcirculatory and molecular technology to culture cardiomyocytes from
      different parts of the neonate Wistar rat's heart and record their spontaneous
      pulsation under time-lapse video microscopy, then analyze their activity and
      inspect their survival rate and apoptotic rate under natural and nitric oxide
      conditions. The pulsation frequency in cardiomtocytes of different parts in heart
      are: 78.5+/-11.0 beats/min in the atrium, 88.4+/-6.3 beats/min in the left
      ventricle, 90.3+/-7.9 beats/min in the right ventricle and 115.3 +/-11.4
      beats/min in the cardiac apex, respectively, with an average frequency of 81.3
      beats/min. Different concentrations of nitric oxide showed no effect on the
      frequency of cardiomyocyte pulsation. The survival rates of the above
      cardiomyocytes are 96.0%, 95.0%, 95.0%, and 95.3% respectively and 95.0% for the
      whole heart. The apoptotic rates are 1.3%, 1.1%, 4.8%, and 1.8% respectively and
      5.1% for the whole heart. Different concentrations of nitric oxide had no effect
      on these results. Our study showed that cultured myocardial cells from different
      parts of the heart displayed various pulsation frequencies, and the frequency of
      the cardiac apex is the highest while the atrium is lowest. We also found that
      there is no statistically significant difference in the survival rates and
      apoptotic rates of different parts of the heart, and that nitric oxide has no
      effect on the beating frequency, survival rates or apoptotic rates of the
      cardiomyocytes in vitro.

PMID- 14724364
TI  - The mitogenic and anti-apoptotic activity of tumor conditioned medium on
      endothelium.
AB  - This study was designed to observe the effect of tumor conditioned medium (TCM)
      on the proliferation and apoptosis of human umbilical vein endothelial cells
      (HUVECs). HUVECs were exposed to TCM from breast carcinoma cell line MDA-MB-231,
      then we measured their proliferation, apoptosis and cell cycle distribution by
      MTT and flow cytometery (FCM). Following the stimulation of TCM, HUVECs showed
      higher pro-mitogenic and anti-apoptotic ability than did the negative control
      group (ECGF-free medium with 20% FBS), but a similar ability to the positive
      control group (medium with ECGF and 20% FBS). From these results, we can conclude
      that breast carcinoma cell line MDA-MB-231 could secret soluble pro-angiogenic
      factors that induce HUVEC angiogenic switching, including cell cycle progression,
      proliferation and growth. The role and character of these factors remain to be
      further studied.

PMID- 14724365
TI  - A proteomic study on cell cycle progression of endothelium exposed to tumor
      conditioned medium and the possible role of cyclin D1/E.
AB  - This study was designed to comprehensively analyze the differential expression of
      proteins from human umbilical vein endothelial cells (HUVECs) exposed to tumor
      conditioned medium (TCM) and to identify the key regulator in the cell cycle
      progression. The HUVECs were exposed to TCM from breast carcinoma cell line MDA
      MB-231, then their cell cycle distribution was measured by flow cytometer (FCM).
      The role of protein in cell cycle progression was detected via two-dimensional
      polyacrylamide gel electrophoresis (2-DE) and western blotting. Following the
      stimulation of TCM, HUVECs showed a more cells in the S phase than did the
      negative control group (ECGF-free medium with 20% FBS), but the HUVECs' level was
      similar to the positive control group (medium with 25 micrograms/ml ECGF and 20%
      FBS). Increased expression of cyclin D1/E and some changes in other related
      proteins occurred after incubation with TCM. From our results, we can conclude
      that breast carcinoma cell line MDA-MB-231 may secrete soluble pro-angiogenic
      factors that induce the HUVEC angiogenic switch, during which the expression of
      cell cycle regulator cyclin D1/E increases and related proteins play an important
      role in this process.

PMID- 14724366
TI  - L-arginine improves cerebral blood perfusion and vasomotion of microvessels
      following subarachnoid hemorrhage in rats.
AB  - The purpose of this study is to investigate the effect of L-arginine (L-Arg) on
      cerebral blood perfusion and vasomotion (perfusion motion) in microvessels
      following subarachnoid hemorrhage (SAH). Rat noncraniotomy SAH models were used
      and animals were divided into sham-operated, saline-treated, and L-Arg-treated
      groups. L-Arg was injected intraperitoneally 30 minutes before the operation and
      repeated every 6 hours, with a single dose of 0.5 g/kg bw. Dynamic changes in
      regional cerebral blood flow (CBF) and vasomotion within 24 hours were measured
      using a laser Doppler flow-meter probe. Serum nitric oxide (nitrite/nitrate) and
      plasma endothelin-1 levels were also measured at different time points within 24
      hours. Morphologic changes in neurons in the hippocampus CA1 region were
      examined. SAH gave rise to an immediate and persistent decrease in CBF in saline
      treated rats. Abnormal vasomotions with decreased frequency and amplitude were
      observed. Serum nitric oxide decreased, while plasma endothelin-1 increased
      significantly. Neurons in the hippocampus CA1 region were severely damaged. The
      above pathological alterations in the L-Arg-treated group were alleviated. It was
      concluded that L-Arg, which increases cerebral blood perfusion and improves
      vasomotions of microvessels by enhancing nitric oxide levels and decreasing
      endothelin-1 levels in blood, exerts a protective effect on secondary cerebral
      ischemic injury following experimental SAH.

PMID- 14724367
TI  - Decreased agglutinability of human erythrocytes by attachment of methoxy
      polyethylene glycol and the effect on erythrocyte oxygen-carrying ability.
AB  - In the interest of creating readily transfusable blood, we have developed a
      method of covalently bonding methoxy polyethylene gylcol (mPEG) to the
      erythrocyte membrane to mask antigens which would otherwise cause immunorejection
      in unmatched blood transfusions. Previous studies have reported the ability of
      mPEG to mask erythrocyte antigens without significantly affecting viability,
      morphology, deformability, and other membrane functions. Our spectrophotometric
      analysis of modified erythrocytes has shown that as well as its other properties,
      mPEG-coated red blood cells can still take up oxygen, while remaining
      antigenically silent.

PMID- 14724368
TI  - Is microvascular flow rate related to ghrelin, leptin and adiponectin levels?
AB  - Ghrelin, leptin and adiponectin are three hormones which are frequently
      associated with metabolism, obesity and appetite. Recently, it has been shown
      that they may possess other physiologic roles, specially in connection with the
      circulation. Ghrelin infusion increases forearm blood-flow in a dose-dependent
      manner. Leptin has been shown to be involved not only in thermogenesis but
      angiogenesis as well. Adiponectin, apart from its insulin-sensitizing action,
      appears to modulate inflammation by inhibiting monocyte adhesion to endothelial
      cells. Six monkeys, which had been classified as being in the pre-diabetic state,
      where administered a triglyceride lowering regimen. Microvascular function was
      assessed using a laser Doppler flow-meter during a temperature provocation test.
      Percent change in flow from baseline following temperature elevation, as well as
      percent change in flow/degree rise in temperature were used to evaluate
      microvascular reserve and reactivity. Using univariate analysis, it appears that
      increased perfusion is significantly correlated with adiponectin, followed by
      leptin. Flow was also positively correlated with ghrelin, but the relationship
      did not attain significance. As expected, flow was also negatively and
      significantly correlated with fibrinogen. Trends show that flow was also
      negatively correlated to circulating triglyceride levels (p=0.08). The data
      indicate that the three hormones appear to possess microvascular actions that may
      impact on their other physiologic functions.

PMID- 14724369
TI  - Maturity of pericytes in cerebral neocapillaries induced by growth factors:
      fluorescence immuno-histochemical analysis using confocal laser microscopy.
AB  - The maturity of pericytes in cerebral neocapillaries induced by two different
      growth factors: basic fibroblast growth factor (bFGF) and platelet-derived growth
      factor (PDGF), was examined using an immunohistochemical staining technique.
      Cerebral angiogenesis was induced in mice by implanting a sandwich system of
      bFGF/PDGF gel and nylon-mesh over the exposed cortex. On 28th day after
      incubation, a small volume of cerebral tissue with the nylon-mesh was isolated
      and stained using tetramethyl rhodamine isothiocyanate (TRITC)-labeled secondary
      antibody to the primary antibody against NG_2 proteoglycan and fluorescein
      isothiocyanate (FITC)-labeled Griffonia simplicifolia (GS)-lectin. Using a
      confocal laser microscopic system, we observed the cerebral neocapillaries on the
      upper surface of the nylon-mesh and evaluated the maturity of pericytes stained
      with NG_2 based on the fluorescence immunohistological images. The pericyte
      appeared rich in neocapillaries induced by PDGF. It was suggested that pericytes
      might play a key role in the regulation of blood flow in neovessels.

PMID- 14724370
TI  - Endothelial nitric oxide synthase expression in systemic and pulmonary
      circulation of streptozotocin induced diabetic rats: comparison using image
      analysis.
AB  - To compare the level of endothelial nitric oxide synthase (eNOS) expression
      produced in heart and lung vascular tissue, the protein content was determined
      using Western blot analysis with the enhancement of image processing. Heart and
      lung extracts from 12 and 24 weeks from control (CON) and streptozotocin-induced
      diabetic (DM) rats were collected for Western blot analysis. Using monoclonal
      antibody against rat eNOS protein (140 kDa), the eNOS-protein bands were detected
      with enhanced chemiluminescence (ECL; Amersham) and exposured to film (Hyperfilm
      ECL; Amersham). Images of eNOS bands on each film were then scanned and saved to
      digital files. Using Global Lab Image software, the number of pixels in each
      digital file was counted and calibrated for eNOS-protein content. For the CON and
      DM groups, the mean values of eNOS-protein contents were calculated and expressed
      as a percentage of total protein content, 5 micrograms. It was found that the
      eNOS level in DM hearts was significantly decreased, as compared to age-matched
      CON hearts. On the other hand, eNOS levels in DM lungs was increased, compared to
      CON lungs. Therefore, it may be concluded that high, not low, flow-mediated eNOS
      expression is a good measure of hyperglycemic-induced endothelial dysfunction.

PMID- 14724371
TI  - Short-term effects of an intensive lifestyle modification program on lipid
      peroxidation and antioxidant systems in patients with coronary artery disease.
AB  - The purpose of this study was to compare the short-term effects of an intensive
      lifestyle modification (ILM) program on lipid peroxidation and antioxidant
      systems in patients with coronary artery disease (CAD). Twenty-two patients in
      the control group continued to receive their conventional treatment with lipid
      lowering drugs, whereas 22 patients in the experimental group were assigned to
      intensive lifestyle modification (ILM) without taking any lipid-lowering agent.
      The ILM program comprised dietary advice on low-fat diets, high antioxidants and
      high fiber intakes, yoga exercise, stress management and smoking cessation. After
      4 months of intervention, patients in the experimental group revealed a
      statistically significant increase in plasma total antioxidants, plasma vitamin E
      and erythrocyte glutathione (GSH) compared to patients in the control group.
      There was no significant change in plasma malondialdehyde (MDA), a circulating
      product of lipid peroxidation, in either group. We concluded that the ILM program
      increased circulating antioxidants and reduced oxidative stress in patients with
      CAD.

PMID- 14724372
TI  - Alleviation of brain edema by L-arginine following experimental subarachnoid
      hemorrhage in a rat model.
AB  - Decreased levels of nitric oxide play a role in the development of cerebral
      ischemia secondary to subarachnoid hemorrhage (SAH). The protective effect of L
      arginine on brain edema following SAH was investigated in this study. Rats were
      divided randomly into a sham-operated, a SAH+saline group and a SAH+L-arginine
      group. At different time points, brain water content was determined using the wet
      and dry weight compared method. Brain sodium content, potassium content and
      calcium content were detected using an atomic absorption spectral photometer.
      Somatosensory evoked potentials (SEP) were also detected. It was found that rat
      SAH models were successfully replicated. In the SAH+saline group, brain water and
      sodium content were significantly higher at 6 h and 24 h than those in the sham
      operated group, while brain potassium content was statistically lower than that
      in the sham-operated group. Brain calcium content increased from 1 h to 24 h
      after induction of SAH. SEP latency progressively delayed. In the SAH+L-arginine
      group, increases in brain water content, sodium content and calcium content, as
      well as decreases in brain potassium content, were not as obvious as in the
      SAH+saline group. L-arginine partly prevented a delay in SEP latency. In
      conclusion, L-arginine, a substrate of nitric oxide synthesis, may relieve brain
      edema in rats with experimental SAH.

PMID- 14724373
TI  - Measurement of red cell velocity in microvessels using particle image velocimetry
      (PIV).
AB  - A new technique using particle image velocimetry (PIV) has been developed to
      evaluate the detailed velocity profiles of red cells flowing in microvessels. The
      microcirculation in rat mesentery was directly observed using high-speed
      videomicroscopy, and the images of red cells flowing in the mesenteric arterioles
      were recorded simultaneously with the arterial blood pressure. Based on the high
      speed videomicroscopic images obtained, velocity vectors in single or branched
      arterioles were evaluated to obtain velocity profiles across the cross-section of
      arterioles. It was shown that in single and straight arterioles the velocity
      profile was blunt with a pit at the central region, and its pit was marked in
      bifurcation. The present technique enables us to analyze red cell velocity
      profiles up to 0.8 microm in the spatial resolution and 1 msec in the time
      interval.

PMID- 14724374
TI  - Artificial neural network analysis of malaria severity through aggregation and
      deformability parameters of erythrocytes.
AB  - The erythrocyte aggregation and deformability of blood samples obtained from
      normal subjects and malaria patients are determined by microscopic imaging and
      laser aggregometry techniques, and optical hemorheometer, respectively. By these
      techniques several parameters are determined but four parameters, aggregate
      sedimentation velocity (ASV), effective number of cells (ENC), process completion
      time (PCT) and mean filtration time (MFT), show significant variation in malaria
      patients compared to that of healthy subjects. For malaria severity analysis
      artificial neural network (ANN), based on feedforward-error back-propagation
      algorithm in a supervisory training mode is proposed. This network is first
      trained for different number of epochs ranging from 20 to 50 by set of patterns
      and at 30 epochs training session the minimum mean square error (MSE) between
      desired and actual output is obtained. By applying the same procedure the test
      patterns belonging to normal, non-severe, severe, and highly severe malaria (NSM,
      SM and HSM) are identified. The results show that malaria with high severity is
      classified accurately (100%). The success of classification for non-severe and
      mildly-severe malaria ranges from 60% to 80%.

PMID- 14724375
TI  - Glomerular endothelial cytotoxicity and dysfunction in nephrosis with focal
      segmental glomerulosclerosis.
AB  - Glomerular endothelial cell dysfunction (GED) with defective release of
      vasodilator has been delineated in nephrosis (NS) in vivo and in vitro studies.
      In NS with focal segmental glomerulosclerosis (FSGS), an immunocirculatory
      balance may be impaired due to defective anti-inflammatory cytokine. This study
      aimed at simultaneous determination of both proinflammatory cytokine (tumor
      necrosis factor alpha) and an anti-inflammatory cytokine (interleukin-10) in NS
      with FSGS. An endothelial cell cytotoxicity (ECC) was also examined using
      nephrotic serum. It was shown that (1) the initial endothelial cell cytotoxicity
      was significantly different from the control, (2) ratio between tumor necrosis
      alpha and interleukin-10 was significantly elevated, and (3) intrarenal
      hemodynamics was changed significantly.

PMID- 14724376
TI  - Neuroprotective actions of Selegiline in inhibiting 1-methyl, 4-phenyl,
      pyridinium ion (MPP+)-induced apoptosis in SK-N-SH neurons.
AB  - We have examined mitochondrial membranes and molecular hallmarks of apoptosis in
      response to increasing concentrations of 1-Methyl, 4-phenyl, Pyridinium ion
      (MPP(+)) in SK-N-SH neurons and have evaluated the neuroprotective potential of
      Selegiline with a primary objective to explore its mechanism(s) of
      neuroprotection. MPP(+)-induced apoptosis was characterized by spherical
      appearance, suppressed neuritogenesis, phosphatidyl serine externalization,
      plasma membrane perforations, mitochondrial membrane potential (Delta Psi)
      collapse, mitochondrial aggregation, and nuclear DNA fragmentation and
      condensation. At lower concentrations, MPP(+) (10-100 microM) produced
      mitochondrial swelling and loss of cristae, and at higher concentrations (300-500
      microM), degeneration and aggregation of mitochondrial membranes in the peri
      nuclear region, which were attenuated by Selegiline (10-50 microM) pre-treatment.
      At still higher concentrations, MPP(+) (>500 microM) produced necrotic changes
      represented by mitochondrial and plasma membrane ballooning and perforations.
      Selegiline provided partial neuroprotection at higher concentrations of MPP(+).
      MPP(+)-induced increases in reactive oxygen species, lipid peroxidation,
      cytochrome-C release, necrosis factor kappa-B (NF-kappa-B) activation, 8-hydroxy,
      2 deoxy guanosine synthesis, alpha-synuclein indices, and reductions in
      glutathione, ATP, and superoxide dismutase were attenuated by Selegiline.
      Selegiline also attenuated MPP(+)-induced transcriptional activation of c-fos, c
      jun, GAPDH, and caspase-3, suggesting that it may provide neuroprotection by
      preserving mitochondrial membranes, by attenuating molecular markers of
      apoptosis, by scavenging free radicals, and by regulating immediate early genes
      involved in neurodegeneration.

PMID- 14724377
TI  - Sema3A and neuropilin-1 expression and distribution in rat white adipose tissue.
AB  - Semaphorins are cell surface and/or soluble signals that exert an inhibitory
      control on axon guidance. Sema3A, the vertebrate-secreted semaphorin, binds to
      neuropilin-1, which together with plexins constitutes the functional receptor. To
      verify whether Sema3A is produced by white adipocytes and, in that case, to
      detect its targets in white adipose tissue, we studied the cell production and
      tissue distribution of Sema3A and neuropilin-1 in rat retroperitoneal and
      epididymal adipose depots. Sema3A and neuropilin-1 were detected in these depots
      by Western blotting. The immunohistochemical results showed that Sema3A is
      produced in, and possibly secreted by, smooth muscle cells of arteries and white
      adipocytes. Accordingly, neuropilin-1 was found on perivascular and parenchymal
      nerves. Such a pattern of distribution is in line with a role for secreted Sema3A
      in the growth and plasticity of white adipose tissue nerves. Indeed, after
      fasting, when white adipocytes are believed to be overstimulated by noradrenaline
      and rearrangement of the parenchymal nerve supply may occur, adipocytic
      expression of Sema3A is reduced. Finally, the presence of neuropilin-1 in some
      white adipocytes raises the interesting possibility that Sema3A also exerts an
      autocrine-paracrine role on these cells.

PMID- 14724378
TI  - Neonatal deafening causes changes in Fos protein induced by cochlear electrical
      stimulation.
AB  - The influence of neonatal deafness on cochlear electrically evoked Fos expression
      in the auditory brainstem was examined. Newborn rats were deafened by systemic
      injection of kanamycin, 1 mg/g daily for 12 days. At 4, 5, 6 or 8 weeks of age,
      these animals received cochlear electrical stimulation with a basal monopolar
      electrode for 90 minutes. Age-matched untreated control animals received similar
      stimulation. Experimental and control animals were assessed for spiral ganglion
      cell densities and Fos immunoreactive staining in the central nucleus of the
      inferior colliculus. Spiral ganglion cell assessments showed significant
      decreases in spiral ganglion cell densities in deafened rats compared to age
      matched controls, at 5 weeks of age in lower turns and 6 and 8 weeks in all
      turns. Cochlear electrical stimulation induced Fos immunoreactive staining in the
      nucleus of auditory brain stem neurons in treatment and control groups. A
      significantly greater number of Fos immunoreactive neurons was found in the
      contralateral central nucleus of inferior colliculus in 5, 6 and 8 week old
      deafened animals compared to age-matched controls. The increases were larger with
      a longer duration of deafness. These results suggest that there are changes in
      auditory processing as a consequence of neonatal deafness.

PMID- 14724379
TI  - The three-dimensional microanatomy of Meissner corpuscles in monkey palmar skin.
AB  - The Meissner corpuscle is a rapidly-adapting mechanoreceptor in the dermal
      papillae of digital skin. For an analysis of how the sensory endings detect
      tissue deformations, an examination of their fine structure and relationships
      with dermal collagen was carried out in the Japanese monkey, Macaca fuscata,
      using a combination of three methods: SEM of cell architecture denuded by 6N
      sodium hydroxide maceration, SEM of collagen networks exposed by a mild alkaline
      corrosion, and TEM according to a conventional procedure. Observations showed the
      sensory corpuscles to be represented by a stack of discoid components consisting
      of flattened axon terminals sandwiched between Schwann cell lamellae, as reported
      previously. Each corpuscle was entirely covered by a connective tissue capsule,
      which was linked with the basal aspect of the epidermis by dermal collagen
      fibers. Margins of the discoid components of the corpuscles were serrated with
      numerous fine projections of lamellar Schwann cells, which tightly held collagen
      trabeculae on the inner aspect of the pericorpuscular capsule. Central portions
      of the discoids, on the other hand, displayed extremely smooth surfaces, which
      were covered by a thick layer of basal lamina-like matrix. The former portions of
      the discoids appear susceptible to mechanical deformations of surrounding
      tissues, while the latter may follow the tissue movements rather slowly because
      of their indirect linkage with the dermal collagen network. The resulting
      distortions of the axon endings during dynamic phases of the tissue deformations
      will be in favor of the generation of rapidly adapting receptor potentials in the
      sensory corpuscle.

PMID- 14724380
TI  - 5-HT2a receptors in rat sciatic nerves and Schwann cell cultures.
AB  - Pharmacological approaches and optical recordings have shown that Schwann cells
      of a myelinating phenotype are activated by 5-HT upon its interaction with the 5
      HT(2A) receptor (5-HT(2A)R). In order to further characterize the expression and
      distribution of this receptor in Schwann cells, we examined rat sciatic nerve and
      cultured rat Schwann cells using probes specific to 5-HT(2A)R protein mRNA. We
      also examined the endogenous sources of 5-HT in rat sciatic nerve by employing
      both histochemical stains and an antibody that specifically recognizes 5-HT. Rat
      Schwann cells of a myelinating phenotype contained both 5-HT(2A)R protein and
      mRNA. In the healthy adult rat sciatic nerve, 5-HT(2A)Rs were evenly distributed
      along the outermost portion of the Schwann cell plasma membrane and within the
      cytoplasm. The most prominent source of 5-HT was within granules of the
      endoneurial mast cells, closely juxtaposed to Schwann cells within myelinating
      sciatic nerves. These results support the hypothesis that the 5-HT receptors
      expressed by rat Schwann cells in vivo are activated by the release of 5-HT from
      neighboring mast cells.

PMID- 14724382
TI  - Microvacuolar neuronopathy: a postmortem artifact of sensory neurons.
AB  - Vacuolar changes in primary sensory neurons have been described in the context of
      disease and injury. In this work we examine microvacuolation of rat dorsal root
      ganglion (primary sensory) neurons. This change, attributed to swelling of
      mitochondria, had a direct relationship with the duration of the post mortem
      interval prior to harvesting. Similar microvacuolation, but also the presence of
      subplasmalemmal scalloping was prominent in dorsal root ganglion samples from
      patients without known peripheral disease undergoing post mortem examination.
      Both types of vacuolar change differ from "signet ring" vacuolation linked to
      neuron injury or disease. We suggest that care is required in evaluating vacuolar
      changes in primary sensory neurons. Microvacuolation is probably not a feature of
      sensory neuron disease.

PMID- 14724381
TI  - Schwann cell dynamics with respect to newly formed motor-nerve terminal branches
      on mature (Bufo marinus) muscle fibers.
AB  - A study has been made of the formation of synaptic terminals from long processes
      formed at the end of motor nerve branches of endplates in mature amphibian (Bufo
      marinus) muscle. Injection of fluorescent dyes into individual motor axons showed
      the full extent of their branches at single endplates. Synaptic vesicle clusters
      at these branches were identified with styryl dyes. Some terminal branches
      consisted of well separated varicosities, each possessing a cluster of
      functioning synaptic vesicles whilst others formed by the same axon consisted of
      closely spaced clusters of vesicles in a branch of approximately uniform
      diameter. All the varicosities gave rise to calcium transients on stimulation of
      their parent axon. Both types of branches sometimes possessed short processes (<5
      microm long) or very long thin processes (>10 microm long) which ended in a bulb
      that possessed a functional synaptic vesicle cluster. These thin processes could
      move and form a varicosity along their length in less than 30 min. Injection of a
      fluorescent dye into terminal Schwann cells (TSCs) at an endplate showed that
      they also possessed very long thin processes (>10 microm long) which could move
      over relatively short times (<30 min). Injecting fluorescent dyes into both axons
      and their associated TSCs showed that on some occasions long TSC processes were
      accompanied by a long nerve terminal process and at other times they were not. It
      is suggested that the mature motor-nerve terminal is a dynamic structure in which
      the formation of processes by TSCs guides nerve terminal sprouting.

PMID- 14724384
TI  - Axonal terminals of sensory neurons and their morphological diversity.
AB  - The application of electron microscopy to defining the fine structural
      characteristics of axon terminals and synapses was followed by a half century of
      intensive exploration of the molecular concomitants of synaptic activity. The
      summer of 2003 marks the 50th anniversary of the earliest accounts of synapses by
      Palay and Palade. Prompted by recent findings of specialization in the fine
      structure of nociceptor terminals that lack contacts remotely resembling a
      synapse, we present a survey of arrangements, contacts and axoplasmic contents of
      peripheral sensory axon terminals. The morphological principles underlying the
      variety of small, clear, spherical vesicles, mitochondrial aggregation, the
      membrane thickenings associated with sensory terminals and the organelles or
      inclusions associated with the site of transduction apparently do not conform to
      a simple parsimonious rule. It is also evident that the terminal of the central
      branch of bifurcated sensory axons differs structurally from its distal
      counterparts. This brief illustrated account addresses some important unresolved
      problems in the functional interpretation of the diverse morphological features
      exhibited in both synaptic and non-synaptic sensory axon terminals with the aim
      of identifying and emphasizing some key questions amenable to resolution with
      contemporary morphological and physiological techniques.

PMID- 14724383
TI  - STOP (stable-tubule-only-polypeptide) is preferentially associated with the
      stable domain of axonal microtubules.
AB  - Axonal microtubules consist of two distinct domains that differ in tyrosinated
      tubulin staining. One domain stains weakly for tyrosinated-tubulin, while the
      other stains strongly, and the transition between these domains is abrupt; the
      tyrosinated-tubulin-poor domain is at the minus end of the microtubule, and the
      tyrosinated-tubulin-rich domain extends from the plus end of the tyrosinated
      tubulin-poor domain to the end of the microtubule. The tyrosinated-tubulin-poor
      domain is drug- and cold-stable, whereas the tyrosinated-tubulin-rich domain is
      drug-labile, but largely cold-stable. STOP (stable-tubule-only-polypeptide) has
      potent microtubule stabilizing activity, and may contribute to the cold and drug
      stability of axonal microtubules. To evaluate this possibility, we examined STOP
      association with the different types of microtubule polymer in cultured
      sympathetic neurons. By immunofluorescence, STOP is present in the cell body and
      throughout the axon; axonal staining declines progressively in the distal portion
      of the axon, and reaches lowest levels in the growth cone. Growth cone
      microtubules, which are drug and cold labile, do not stain detectably for STOP.
      To examine individual axonal microtubules for STOP, we used a procedure that
      causes microtubules to splay out from the main axonal array so that they can be
      visualized for relatively long distances along their length. Both tyrosinated
      tubulin-rich and tyrosinated-tubulin-poor polymer stain for STOP, but STOP is
      several-fold more concentrated on tyrosinated-tubulin-poor polymer than on
      tyrosinated-tubulin-rich polymer. These results are consistent with STOP
      dependent stabilization of axonal microtubules, with the difference between cold
      stable polymer versus cold- + drug-stable polymer determined by the amount of
      STOP on the polymer.

PMID- 14724385
TI  - Distribution of mGluR1alpha and SMI 311 immunoreactive Lugaro cells in the kitten
      cerebellum.
AB  - The Lugaro cell is a feedback interneuron of the cerebellar cortex, recognizable
      by its characteristic morphology. Postnatal neuronal migration to the cortex has
      been described for several cerebellar interneurons. Since in our previous studies
      we observed Lugaro-like cells (LCs) in the white matter (WM) and internal
      granular layer (IGL) of the cerebellum of young cats, we assumed that a
      proportion of these cells migrate also postnatally to their destination. In the
      present study using and immunostaining for the metabotropic glutamate receptor
      mGluR1alpha and neurofilament protein SMI 311 the number and spatial distribution
      of LCs at different postnatal days were investigated. We found that the number
      and distribution of both mGluR1a-immunoreactive (ir) and of SMI 311-ir LCs
      changed with age in the developing cerebellar cortex of kittens: developing LCs
      express mGluR1alpha already in the newborn, while expression of SMI 311-ir in LCs
      appears only about a week later. At postnatal day 1 (P1) relatively few mGluR1-ir
      LCs were detected in the WM and at the border of WM and IGL. Later, their number
      increased sharply until P15 (6-7 fold) and decreased continuously between P15 and
      P135. SMI 311-ir LCs were not present at P1 and even at P8 only a few were
      observed in the WM or in infraganglionic positions. Their number increased
      gradually (12-14 fold) until adulthood when their number was stabilized at 8.000
      10.000/cerebellum. At the same time the number of probably ectopic SMI 311-ir LCs
      decreased with age: at P22 about one third of them was found in "ectopic"
      position, whereas in the adult cat only about 10-12% of LCs's was either in the
      WM or scattered in the whole depth of the granular layer. These results suggest
      that: (1) most LCs appear in the cerebellar cortex postnatally; and (2) postnatal
      migration and incorporation of LCs to the cortex is a much longer process than
      previously expected, occurring even after the cytoarchitectonic built-up (about
      P65-P70 in cat) of the cerebellum.

PMID- 14724386
TI  - Effects of congenital deafness in the cochlear nuclei of Shaker-2 mice: an
      ultrastructural analysis of synapse morphology in the endbulbs of Held.
AB  - It is well established that manipulation of the sensory environment can
      significantly alter central auditory system development. For example,
      congenitally deaf white cats exhibit synaptic alterations in the cochlear nucleus
      distinct from age-matched, normal hearing controls. The large, axosomatic endings
      of auditory nerve fibers, called endbulbs of Held, display reduced size and
      branching, loss of synaptic vesicles, and a hypertrophy of the associated
      postsynaptic densities on the target spherical bushy cells. Such alterations,
      however, could arise from the cat's genetic syndrome rather than from deafness.
      In order to examine further the role of hearing on synapse development, we have
      studied endbulbs of Held in the shaker-2 ( sh2 ) mouse. These mice carry a point
      mutation on chromosome 11, affecting myosin 15 and producing abnormally short
      stereocilia in hair cells of the inner ear. The homozygous mutant mice are born
      deaf and develop perpetual circling behavior, although receptor cells and primary
      neurons remain intact at least for the initial 100 days of postnatal life.
      Endbulbs of Held in 7-month old, deaf sh2 mice exhibited fewer synaptic vesicles
      in the presynaptic ending, the loss of intercellular cisternae, and a hypertrophy
      of associated postsynaptic densities. On average, postsynaptic density area for
      sh2 endbulbs was 0.23 +/- 0.19 microm(2) compared to 0.07 +/- 0.04 microm(2) ( p
      < 0.001) for age-matched, hearing littermates. These changes at the endbulb
      synapse in sh2 mice resemble those of the congenitally deaf white cat and are
      consistent with the idea that they represent a generalized response to deafness.

PMID- 14724387
TI  - Matching neural morphology to molecular expression: single cell injection
      following immunostaining.
AB  - To match a neuron's morphology with its expression of a particular protein, it is
      useful to first identify the cell by immunostaining and then inject it with
      fluorescent dye. Such targeted injection cannot be performed with a hydrophilic
      dye (such as Lucifer yellow) because the neuron, once rendered porous to
      antibodies, does not retain it. But a lipophilic dye (such as DiI) injected
      iontophoretically into the soma forms a crystal and is thereby trapped. From this
      intracellular depot dye diffuses into the cell membrane to reveal the detailed
      morphology. We have used this strategy to identify the morphology of a GABAergic
      retinal bipolar cell and several types of GABAergic amacrine cell. In addition,
      we demonstrate probable connections from a narrow-field, GABAergic amacrine cell
      to the OFF brisk-transient ganglion cell. Finally, we show that the strategy
      works in the cortical slice, showing a layer IV cell immunostained for
      parvalbumin to be a "nest basket cell".

PMID- 14724388
TI  - Morphology and monoaminergic modulation of Crustacean Hyperglycemic Hormone-like
      immunoreactive neurons in the lobster nervous system.
AB  - Neuronal somata located near branch points in the second thoracic nerve roots of
      the lobster are immunoreactive for Crustacean Hyperglycemic Hormone (CHH)-like
      peptides, a family of putative stress hormones. We have employed intracellular
      dye injection, immunostaining, and confocal imaging to observe the anatomy of
      these root neurons, which are morphologically diverse and dye coupled. Some root
      neurons contribute to neurosecretory structures at the points of exit of the root
      from the nerve cord. Other CNS-projecting root neurons send projections into the
      T5-A1 interganglionic connectives. Neurosecretory elements of the serotonin (5HT)
      and octopamine (OCT) systems, implicated in postural control and aggression,
      terminate densely in the vicinity of the second thoracic root neurons. We have
      confirmed by double immunostaining for 5HT and CHH-like peptides that the endings
      of the 5HT neurons are in close apposition to root neurons in the superficial
      regions of the root. We have also extended previous studies documenting
      electrophysiological responses of the root neurons to 5HT or OCT. Bath-applied
      5HT and OCT inhibit the spontaneous bursting activity of root neurons at
      concentrations higher than 100 nM. The root neurons desensitize to the persistent
      presence of high concentrations of 5HT, but not OCT, in the bath. Nanomolar
      concentrations of OCT, but not 5HT have an excitatory effect on the spontaneous
      bursting activity of root neurons. This region of the lobster nervous system is
      of continuing interest, as identified neurons of three neuromodulatory systems
      implicated in stress and aggression converge and interact at the level of
      identified neurons.

PMID- 14724389
TI  - Antibody-mediated CNS demyelination II. Focal spinal cord lesions induced by
      implantation of an IgM antisulfatide-secreting hybridoma.
AB  - We showed previously that spinal cord implants of hybridoma cells (O1) that
      secrete an IgM antigalactocerebroside cause focal multiple-sclerosis-like plaques
      of demyelination followed by remyelination to form "shadow plaques" (Rosenbluth
      et al., 1999). The antibody in that case was directed against a glycolipid
      present in mature oligodendrocytes and myelin but not in precursor cells. We now
      report the effects of implanting a different hybridoma (O4) that secretes IgM
      antibodies directed against sulfatide, a constituent not only of mature myelin
      and oligodendrocytes but also of late precursor cells, in order to determine
      whether this hybridoma too would generate focal demyelination and would, in
      addition, block remyelination. Our results show that focal plaques of
      demyelination indeed appear after O4 implantation, and that remyelination does
      occur, but only in cases where the hybridoma cells have degenerated, probably
      through host rejection. The occurrence of remyelination suggests that
      oligodendrocyte precursor cells are capable of migrating in rapidly from adjacent
      areas or that early precursors, not yet expressing sulfatide, remain undamaged
      within the lesions. In cases where intact hybridoma cells persist at lesion
      sites, remyelination does not occur. Failure of remyelination in this model thus
      appears to result from the continuing presence of antimyelin antibodies rather
      than from depletion of oligodendrocyte precursors.

PMID- 14724390
TI  - Porocytosis: secretion from small and medium-diameter vesicles and vesicle arrays
      without membrane fusion.
AB  - We have recently proposed a mechanism to describe secretion, a fundament process
      in all cells. That hypothesis, called porocytosis, embodies all available data,
      and encompasses both forms of secretion, i.e., vesicular and constitutive. The
      current accepted view of exocytotic secretion involves the physical fusion of
      vesicle- and plasma membranes. However, that hypothesized mechanism does not fit
      all available physiological data (Silver et al., 2001; Kriebel et al., 2001).
      Energetics of apposed lipid bilayers do not favor unfacilitated fusion. Calcium
      ion levels are elevated in microdomains at levels of 10(-4)-10(-3)M for 1 ms or
      less, with the calcium ions showing limited lateral mobility at the site of
      secretion (Llinas et al., 1992, Silver et al., 1994). We consider that calcium
      ions, whose mobility is restricted in space and time, establish "salt-bridges"
      among adjacent lipid molecules, and establishes transient pores that span the
      vesicle and plasma membrane lipid bilayers; the lifetime of that transient pore
      being completely dependent on duration of sufficient calcium ion levels.

PMID- 14724391
TI  - Ultrastructural organization of GABA-like immunoreactive profiles in the weaver
      substantia nigra.
AB  - GABA-like immunoreactivity (GABA-LI) in the substantia nigra pars compacta (SNc)
      of mutant weaver mice was investigated at the electron microscope level. Eight
      week-old homozygous mutant weaver mice, paired with wildtype littermates as
      controls, were perfused with a buffered paraformadehyde/acrolein solution.
      Sections containing the SN were immunocytochemically reacted with an antiserum to
      GABA using the peroxidase-antiperoxidase (PAP) procedure. Ultrastructural
      examination revealed that profiles of GABA-LI dendrites were decreased in number
      while profiles of labeled axonal processes were increased. In addition, there
      were an increased number of GABA-LI terminals in contact with similarly labeled
      GABA-LI dendrites. Double-labeling experiments using the antibodies to GABA and
      dopamine D(2) receptors showed that a small number of GABA-LI profiles exhibited
      D(2)-like immunoreactivity in both controls and weavers. These results suggest
      that the GABA-LI synaptic connections are altered as a result of the loss of DA
      neurons in the SNc of the weaver mice.

PMID- 14724392
TI  - Localization of the type 1 corticotropin releasing factor receptor (CRF-R1) in
      the embryonic mouse cerebellum.
AB  - Corticotropin releasing factor (CRF) is present in the adult, as well as in the
      embryonic and postnatal rodent cerebellum. Further, the distribution of the type
      1 CRF receptor has been described in adult and postnatal animals. The focus of
      the present study is to determine the distribution and cellular relationships of
      the type 1 CRF receptor (CRF-R1) during embryonic development of the cerebellum.
      Between embryonic day (E)11 and E12, CRF-R1 immunoreactive puncta are uniformly
      distributed in the ventricular zone, the site of origin of Purkinje cells,
      nuclear neurons, and GABAergic interneurons, as well as the germinal trigone, the
      birthplace of the precursors of granule cells. Between E13 and 18, the
      distribution of immunolabeled puncta decreases in both the ventricular zone and
      the germinal trigone and increases in the intermediate zone, as well as in the
      dorsal aspect of the cerebellar plate. Between E14 and 18, antibodies that label
      specific populations of cerebellar neurons were combined with the antibody for
      the receptor to determine the cellular elements that expressed CRF-R1. At E14,
      CRF-R1 immunoreactivity is co-localized in neurons immunolabeled with PAX-2, an
      antibody that is specific for GABAergic interneurons. These neurons continue to
      express CRF-R1 as they migrate dorsally toward the cerebellar surface. Between
      E16 and 18, Purkinje cells, immunolabeled with calbindin, near the dorsal surface
      of the cerebellum express CRF-R1 in their cell bodies and apical processes. CRF
      has been shown to have a depolarizing effect on adult and postnatal Purkinje
      cells. Further, CRF has been shown to contribute to excitability of hippocampal
      neurons during embryonic development by binding to CRF-R1; depolarization induced
      excitability appears to be critical for cell survival. The location of the type
      one CRF receptor and the presence of its primary ligand, CRF, in the germinal
      zones of the cerebellum and in migrating neurons suggest that this
      receptor/ligand interaction could be important in the regulation of neuronal
      survival through cellular mechanisms that lead to depolarization of embryonic
      cerebellar neurons.

PMID- 14724393
TI  - Ensheathment of the olfactory nerves in the adult rat.
AB  - The ensheathment of the olfactory nerve fibres is achieved by cooperation of two
      cell types. The olfactory ensheathing cells have a rounded outer surface enclosed
      in a continuous single basal lamina, and enclose an inner compartment from which
      overlapping processes of the same and adjacent cells enwrap interweaving
      territories of tightly apposed aligned axons. The olfactory nerve fibroblasts are
      highly flattened, dense cells generating multiple layers of very thin processes
      encircling individual or groups of olfactory ensheathing cells. This paper
      illustrates the unique ultrastructural features of this ensheathment.

PMID- 14724395
TI  - Uncertainty in medicine: still very much with us in 2004.

PMID- 14724396
TI  - Willingness to participate in cardiac trials.
AB  - The elderly, women, and minorities are all less likely to be enrolled in
      randomized clinical trials (RCTs). Whether differential patient interest in RCTs
      contributes to these disparities is unclear. The authors surveyed 660 patients
      willingness to consider two potential cardiac RCTs of medical therapy vs.
      percutaneous coronary angioplasty or coronary artery bypass surgery,
      respectively. The cohorts mean age was 67 years (43% aged >or=70 years; 35%
      women; and 28% nonwhite). Compared with younger patients, those aged >or=70 years
      were equal or more likely to consider both the percutaneous coronary angioplasty
      (46% vs. 41%) and coronary artery bypass surgery RCTs (35% vs. 31%). Race also
      had no significant impact on trial enrollment, yet women were significantly less
      likely than men to participate in either RCT. In conclusion, patient willingness
      to consider RCT participation does not explain underenrollment of elderly and
      minority patients. Women, however, were more reluctant to consider RCTs, an area
      requiring further study.

PMID- 14724397
TI  - Diastolic heart failure: a difficult problem in the elderly.
AB  - Heart failure with normal systolic function has been equated to diastolic heart
      failure (DHF). DHF appears to be quite common in the elderly, especially in
      elderly women with hypertension. Recent epidemiologic studies suggest that 30%
      50% of patients with heart failure may have DHF. Morbidity for DHF is
      considerable and comparable to that of heart failure with left ventricular
      systolic dysfunction. Both groups of patients have similar rates of recurrent
      hospitalization and cost of care. Long-term mortality also appears to be similar
      in the two groups of patients. With the aging of the population, the numbers of
      patients with DHF will continue to rise and are likely to contribute
      significantly to the burden of disease caused by heart failure. Unfortunately, as
      yet, no reliable definition has been found for DHF. Currently the diagnosis of
      DHF is often made by exclusion, and treatment is empirical and unsatisfactory
      because of the lack of large-scale, randomized, controlled trials in this area;
      however, several large and other smaller trials are currently in progress that
      will hopefully provide some answers.

PMID- 14724398
TI  - Alcohol consumption and abnormalities of brain structure and vasculature.
AB  - Research on how alcohol consumption influences the structure and blood supply of
      the brain has generally focused on two primary areas of interest: the atrophic
      effect of heavy drinking on brain structure and the effects of moderate and heavy
      drinking on the risk of stroke. Heavy alcohol consumption results in atrophy of
      gray and white matter, particularly in the frontal lobes, cerebellum, and limbic
      structures. Heavy drinking also raises the risk of ischemic and hemorrhagic
      stroke, while light drinking is associated with a lower risk of ischemic stroke.
      Recently, the author and his colleagues studied alcohol consumption and
      prevalence of subclinical abnormalities detected by magnetic resonance imaging of
      the brain among 3376 older adults enrolled in the Cardiovascular Health Study.
      They found that alcohol consumption was positively associated with measures of
      brain atrophy and inversely associated with subclinical infarcts in a dose
      dependent manner. Alcohol consumption and white matter lesions had a U-shaped
      relationship, with the lowest prevalence among those who consumed 1-6 drinks per
      week. Further research is needed to determine how these associations interact to
      influence overall brain function.

PMID- 14724399
TI  - Diastolic dysfunction in the elderly--the interstitial issue.
AB  - Diastolic dysfunction is increasingly recognized as a cause of congestive heart
      failure. Meta-analyses of earlier studies of this disorder suggest that 40%-50%
      of patients with the congestive heart failure syndrome have preserved left
      ventricular systolic function, with current estimates ranging up to 74%. Among
      patients >or=65 years of age with congestive heart failure, 55% of all subjects
      and 67% of women had normal systolic function. Histopathologic evaluation reveals
      a maladaptive remodeling of the interstitium associated with aging, resulting in
      an increase in interstitial collagen content. The interstitium normally plays a
      critical role in the generation of early diastolic suction. When there is a
      significant enough increase in myocardial collagen volume fraction, with its
      increased viscoelastic burden, this normal early diastolic suction is compromised
      and diastolic pressures increase. Left ventricular diastolic dysfunction ensues.
      Neurohumoral abnormalities associated with diastolic dysfunction include
      activation of the renin-angiotensin-aldosterone system, including increased
      elaboration of myocardial aldosterone. This excess of aldosterone appears to play
      a major role in the development of myocardial fibrosis. Recent observations in
      animal models and humans have demonstrated regression of interstitial collagen
      volume fraction in response to inhibition of the renin-angiotensin-aldosterone
      system by angiotensin-converting enzyme inhibitors and aldosterone inhibition,
      with improvement in diastolic function. Therapeutic implications of these
      observations suggest targeting the maladaptive remodeling of the interstitium via
      inhibition of the renin-angiotensin-aldosterone system.

PMID- 14724400
TI  - Atrial myxomas in the elderly: a case report and review of the literature.
AB  - Although rare, atrial myxomas constitute the most common benign cardiac tumor.
      The diagnosis of myxomas in the elderly has traditionally been considered an even
      more unusual phenomenon. Most recently, with the advent of more accurate imaging
      techniques, their incidence in the elderly has been noted to be higher than
      originally described. Atrial myxomas should be included in the differential
      diagnosis of elderly patients presenting with progressive, nonspecific
      constitutional complaints, since early diagnosis and surgical removal can lead to
      quick resolution of symptoms and avoidance of devastating complications like
      peripheral embolism and valve dysfunction.

PMID- 14724401
TI  - Ethical issues in the management of geriatric cardiac patients.

PMID- 14724402
TI  - Percutaneous interventions in the elderly: lessons from two recent trials.

PMID- 14724403
TI  - Three kinds of block.

PMID- 14724405
TI  - A scientific soap opera and winter itch.

PMID- 14724406
TI  - Eponyms in dermatology.

PMID- 14724407
TI  - Jefferson Medical College class of 2007 white coat keynote address.

PMID- 14724408
TI  - Oral lichen planus part II: therapy and malignant transformation.
AB  - Oral lichen planus lesions can cause discomfort, pain, and a burning sensation.
      Therefore, all professionals who deal with the oral cavity must be aware of all
      the therapeutic options for it. This article presents a review of the literature
      on oral lichen planus, focusing on its treatment, and also discusses the
      important and controversial potential for the evolution of oral lichen planus
      into epidermoid carcinoma.

PMID- 14724409
TI  - Maintenance therapy for acne vulgaris: the fine balance between efficacy,
      cutaneous tolerability, and adherence.
AB  - Maintenance therapy is defined as the regular use of appropriate therapeutic
      agents to ensure that acne remains in remission. Topical agents are the mainstay
      of maintenance therapy. A number of topical therapeutic options are available,
      including topical retinoids, benzoyl peroxide, and azelaic acid. The choice of
      topical agents should be based on a number of criteria: efficacy in addressing
      the subclinical microcomedo, which is the precursor lesion for both comedones and
      inflammatory lesions; tolerability, due to the need for application to a broader
      epidermal surface; and other properties that may enhance adherence. Patients may
      be more motivated to use agents that are easily integrated into their lifestyles
      and that have potential "skin-repairing" properties.

PMID- 14724410
TI  - Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in
      relation to geographic locations and in migrant populations.
AB  - Over the past two decades a worldwide increase in the incidence of skin cancer to
      near epidemic proportions has led to increased morbidity and appreciating cost.
      Well known risk factors include UV radiation, x or gamma irradiation, chemical
      carcinogens, genetic aberrations, and immunosuppression. This article reviews and
      analyzes the evidence for UV radiations role in the pathogenesis of nonmelanoma
      skin cancer (NMSC). Observations on the incidence of NMSC among migrants to
      temperate regions show an increase in both basal cell carcinoma and squamous cell
      carcinoma. There is also an increase in NMSC in areas with lower latitudes.
      Irradiation of human skin grafted to animals and animal models that develop NMSC
      lend further support to the role of UV radiation in the pathogenesis of NMSC. In
      the forthcoming Part II of this review, epidemiologic evidence will be presented
      attesting to the relationship between UV radiation and NMSC.

PMID- 14724411
TI  - RAPTIVA (efalizumab).

PMID- 14724412
TI  - Amelanotic lentigo maligna melanoma.

PMID- 14724413
TI  - Keratoacanthoma.

PMID- 14724414
TI  - A case of paracetamol-induced acute generalized exanthematous pustulosis in a
      pregnant woman localized in the neck region.

PMID- 14724415
TI  - Cutaneous hypertrophic lupus erythematosus in a patient with systemic
      involvement.

PMID- 14724416
TI  - Amoebiasis cutis.

PMID- 14724417
TI  - Traumatic transverse leukonychia.

PMID- 14724418
TI  - Salute to the icons of hypertension.

PMID- 14724419
TI  - Antihypertensive utility of perindopril in a large, general practice-based
      clinical trial.
AB  - The authors evaluated, in a community-based open-label trial, the effectiveness
      and safety of perindopril in 13,220 US hypertensive patients and studied how
      physicians adhere to hypertension treatment guidelines. Patients received
      perindopril 4 mg q.d. for 6 weeks. Based on physicians perception of blood
      pressure response, the patient was either maintained on 4 mg or the dose was
      increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean
      sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0
      mm Hg. Further dose titration resulted in a clinically significant reduction in
      blood pressure in all patients with inadequate response on 4 mg at week 6. Blood
      pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The
      subpopulation analyses demonstrated that perindopril monotherapy was effective in
      both men and women, in patients of all ethnicities, and in patients <65 and > or
      =65 years of age. Perindopril was safe and well tolerated in all hypertensive
      subgroups including high-risk patients. Physicians were more attuned to
      controlling diastolic than systolic blood pressure, and their adherence to the
      treatment guidelines was found to be not optimal.

PMID- 14724420
TI  - A statewide primary care approach to cardiovascular risk factor control in high
      risk diabetic and nondiabetic patients with hypertension.
AB  - Patients with multiple cardiovascular risk factors benefit from having them all
      controlled, but this rarely occurs. Fifty-seven primary care providers were
      enrolled in a program to monitor cardiovascular risk factor control. Data were
      obtained on 7315 hypertensives. This analysis focuses on 3460 high-risk
      hypertensives including 2199 with diabetes and 1261 with clinical cardiovascular
      disease. Blood pressures were <140/90 mm Hg and <130/80 mm Hg in only 44.3% and
      20.4% of diabetics and 49.6% and 26.6% nondiabetics, respectively, despite the
      use of an average of 2.7+/-1.8 antihypertensive medications. Among high-risk
      dyslipidemic hypertensives, the low-density lipoprotein cholesterol level was
      <100 mg/dL in only 34% of diabetic and 33% of nondiabetic patients. Among 1696
      diabetic hypertensives, the most recent glycosylated hemoglobin value averaged
      7.5%, with 46.6% less than 7%. Among 805 diabetic, dyslipidemic hypertensives,
      all three risk factors were controlled to goal in only 6.6% with higher rates in
      whites than in African Americans (14.8% vs. 1.6%, p<0.001). An angiotensin
      converting enzyme inhibitor, angiotensin receptor blocker, or both were
      prescribed in 89.9% of diabetic and 70.8% of nondiabetic patients, p<0.05.
      Primary care providers use evidence-based combination therapy in high-risk
      hypertensive patients with and without diabetes. These findings confirm the low
      rates of multiple risk factor control and highlight challenges of reaching
      evidence-based goals in primary care.

PMID- 14724421
TI  - An assessment of racial differences in clinical practices for hypertension at
      primary care sites for medically underserved patients.
AB  - Ethnic disparities in hypertension-related outcomes may relate to differences in
      medical care. This study assessed primary care sites serving low-income patients
      to determine if differences in process and treatment indicators might contribute
      to disparities in outcomes. Eight sites were enrolled with 100,000 patients,
      collectively. Trained nurses abstracted a random sample of medical records for
      diagnoses, laboratory data, medications, and demographic variables. Data were
      obtained on 1250 white and 2786 African-American adults. African Americans were
      more likely (p<0.01) to be hypertensive (44% vs. 23%) and diabetic (16% vs. 8%)
      than whites. African Americans were more likely to have serum creatinine,
      potassium, lipid, and glycosylated hemoglobin values recorded in the medical
      record than whites (p<0.01). African-American hypertensives were more likely
      (p<0.05) than white hypertensives to receive calcium channel blockers,
      angiotensin-converting enzyme inhibitors, diuretics, and combination therapy.
      Thus, there appeared to be little difference in the level of care between the two
      groups. Based on the sites examined, ethnic variations in important process and
      treatment indicators do not explain racial differences in cardiovascular and
      renal outcomes.

PMID- 14724422
TI  - Roundtable discussion: chronotherapy and its importance in the management of
      hypertension.

PMID- 14724424
TI  - Headaches and hypertension: primary or secondary?

PMID- 14724425
TI  - Hypertension treatment: contributions and comments on challenges.

PMID- 14724426
TI  - Isolated systolic hypertension in the young.

PMID- 14724427
TI  - Alloantibody and xenoantibody cross-reactivity in transplantation.
AB  - The recent availability of pigs homozygous for alpha1,3-galactosyltransferase
      gene knockout, and improved immunosuppressive regimens that prevent an elicited
      antibody response, are expected to contribute to significantly increased survival
      of pig organs transplanted into primates, bringing clinical trials of
      xenotransplantation closer. Patients highly sensitized to human leukocyte
      antigens, who may be precluded from obtaining a human donor organ, would be one
      group that might benefit from xenotransplantation. However, there have been few
      studies on whether there is cross-reactivity of anti-human leukocyte antigen
      antibodies with pig antigens. What data there are suggest that such cross
      reactivity exists and that this may be detrimental to the outcome after
      transplantation of a pig organ. Neither is it known whether sensitization after a
      pig xenograft would preclude subsequent allotransplantation, although the data
      available suggest that this will not be the case. Further investigation on allo-
      and xenoantibody cross-reactivity is required.

PMID- 14724428
TI  - Programmed death-1-programmed death-L1 interaction is essential for induction of
      regulatory cells by intratracheal delivery of alloantigen.
AB  - BACKGROUND: Programmed death (PD)-1 has been implicated in peripheral tolerance.
      The authors investigated the roles of PD-1 and its ligands, PD-L1 and PD-L2, in
      the induction of regulatory cells by intratracheal delivery of alloantigen.
      METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of C57BL/10
      (H-2b) splenocytes and administration of monoclonal antibody (mAb) specific for
      PD-1, PD-L1, or PD-L2. Seven days later, C57BL/10 hearts were transplanted into
      the pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of
      splenocytes from the pretreated CBA mice and transplantation of C57BL/10 heart.
      RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median
      survival time [MST], 7 days). Pretreatment with intratracheal delivery of
      C57BL/10 splenocytes prolonged graft survival significantly (MST, 65 days).
      Administration of control immunoglobulin (Ig) G or anti-PD-L2 mAb did not
      significantly affect the prolongation (MST, 72 and 68 days, respectively). In
      contrast, anti-PD-1 or anti-PD-L1 mAb abrogated the prolongation (MST, 18 and 17
      days, respectively). Adoptive transfer from mice pretreated with intratracheal
      delivery of alloantigen plus control IgG or anti-PD-L2 mAb prolonged survival of
      C57BL/10 grafts in secondary CBA recipients (MST, 72 and 56 days, respectively).
      However, concurrent administration of anti-PD-1 or anti-PD-L1 mAb abrogated
      prolonged survival after the adoptive transfer (MST, 14 and 20 days,
      respectively). CONCLUSIONS: PD-1-PD-L1 interaction was essential for induction of
      regulatory cells by intratracheal delivery of alloantigen.

PMID- 14724429
TI  - Adenoviral gene transfer of erythropoietin confers cytoprotection to isolated
      pancreatic islets.
AB  - BACKGROUND: The transfer of cytoprotective genes to isolated pancreatic islets
      may contribute to their enhanced survival in the transplant setting. Our
      laboratory established the expression of functional erythropoietin (EPO)
      receptors throughout pancreatic islets. Because EPO is a cytokine that promotes
      survival, we examined whether adenovirus-mediated gene transfer of EPO would
      result in cytoprotection of human pancreatic islets in culture and in the
      transplant setting. METHODS: Isolated human islets were transduced using an
      adenoviral vector coding for human EPO or green fluorescent protein. Comparison
      of cell death in culture was measured using annexin V-phycoerythrin and propidium
      iodide. Transplantation of transduced islets into diabetic nude mice was used to
      assess the effect of EPO on islet function and in vivo survival. RESULTS:
      Adenoviral delivery of EPO to pancreatic islets resulted in high-level EPO
      synthesis and secretion, which did not affect islet function in vitro or in vivo.
      Islets transduced with EPO were protected from apoptosis in culture and were at a
      functional advantage in vivo when compared with islets transduced with green
      fluorescent protein or untransduced islets. The high level of EPO had a negative
      effect on the blood chemistry of the animals that underwent transplantation.
      CONCLUSIONS: Overexpression of EPO protects islets from destruction and does not
      compromise islet function. Genetic engineering with EPO may be a viable approach
      for improving islet survival and engraftment in the transplant setting, but
      regulation of the gene's expression will be an important prerequisite to this
      strategy.

PMID- 14724430
TI  - Expression of MRP2 and MRP3 during liver regeneration after 90% partial
      hepatectomy in rats.
AB  - BACKGROUND: Small-for-size grafts often cause persistent conjugated
      hyperbilirubinemia in the recipient after adult-to-adult living donor liver
      transplantation, but the cause has not yet been clarified. In physiologic status,
      bilirubin is excreted from hepatocytes to the bile canaliculus by means of
      multidrug resistance protein (MRP) 2 and, in particular circumstances, by means
      of MRP3 to the sinusoidal space. The aim of this study was to research whether
      there is any change in bilirubin excretion pattern during liver regeneration with
      reference to expression of MRP2 and MRP3. METHODS: Sprague-Dawley rats underwent
      sham operation (n=37), 70% hepatectomy (n=38), or 90% hepatectomy (n=37). The
      degree of liver regeneration, total and direct bilirubin, protein synthesis, and
      interleukin (IL)-6 were serially assessed. Expression of MRP2 and MRP3 were
      semiquantified by Western blotting. RESULTS: The proliferating cell nuclear
      antigen labeling index indicated rapid liver regeneration after 70% and 90%
      hepatectomy. Serum levels of total and direct bilirubin increased significantly
      (P<0.05), and conjugated hyperbilirubinemia was proved only in the 90%
      hepatectomy group. Coagulation factor VII dipped but increased as early as 12 to
      24 hr postoperatively in both hepatectomy groups. Plasma IL-6 levels were
      significantly increased in the 90% hepatectomy group (P<0.05). Expression of MRP2
      was decreased and MRP3 was expressed at 36 and 72 hr postoperatively in the 90%
      hepatectomy group, whereas no change was observed in MRP expression in the 70%
      hepatectomy group. CONCLUSIONS: During liver regeneration after critical
      hepatectomy such as 90% hepatectomy, decrease of MRP2 and expression of MRP3 may
      play an important role in postoperative hyperbilirubinemia.

PMID- 14724431
TI  - Coronary oxygen persufflation for heart preservation in pigs: analyses of
      endothelium and myocytes.
AB  - BACKGROUND: Coronary oxygen persufflation (COP) has been shown to prolong heart
      preservation time up to 14 hr in a mature pig model, with excellent recovery
      after orthotopic transplantation. The aim of the present study was to assess the
      structural, metabolic, and functional myocardial and endothelial integrity after
      COP in mature pig hearts. METHODS: Cardioplegic arrest was induced by original
      crystalloid Bretschneider solution (HTK 3h, n=6), modified Bretschneider solution
      (mHTK+COP, n=6), or University of Wisconsin solution (UW+COP, n=6). Hearts were
      stored for 3 (HTK 3h) or 14 hr (mHTK+COP, UW+COP) at 0 degrees to 1 degrees C. In
      addition, COP hearts were persufflated. After heterotopic transplantation and
      reperfusion for 7 days, hearts were analyzed by light microscopy or electron
      microscopy for structural injuries. Endothelial function, cardiac enzymes,
      metabolic parameters, and myocardial water content (MWC) were determined. Six
      recipient hearts served as controls. RESULTS: Quantitative light microscopic
      analyses and semiquantitative electron microscopic analyses showed an equal
      amount of damage in all groups including HTK 3h hearts. No rejection was
      observed. Substance P induced an equal dilatation in all hearts. Serum levels of
      cardiac enzymes were similar in all groups, but energy-enriched phosphates were
      significantly reduced, and MWC was augmented in the HTK 3h hearts and in the
      UW+COP hearts, in contrast to the mHTK+COP transplants. CONCLUSIONS: The lack of
      structural defects related to the COP technique, similar endothelial function,
      and an even better metabolic state of the mHTK+COP hearts versus HTK 3h hearts
      demonstrate the efficacy of the COP technique for prolongation of myocardial
      preservation time up to 14 hr.

PMID- 14724432
TI  - Estrogen regulates insulin-like growth factor 1, platelet-derived growth factor A
      and B, and their receptors in the vascular wall.
AB  - BACKGROUND: Peptide growth factors induce vascular smooth muscle cell (SMC)
      proliferation and migration after vascular injury, leading to arterial stenosis.
      Estrogen provides vasculoprotective effects by regulating endothelial and
      vascular SMC function. METHODS: We performed aortic denudations in male Wistar
      rats. One group received 17beta-estradiol, 0.25 mg/kg per day subcutaneously, and
      the other group vehicle. Growth factor and receptor mRNA in the aorta wall was
      quantitated at 15 minutes, 3 days, and 7 days after denudation. Western blotting
      and immunohistochemistry were used to quantify and localize the protein. RESULTS:
      Aortic injury caused SMC proliferation in the intima and media, indicated by an
      increase in the number of intimal nuclei and area. Quantitative reverse
      transcriptase polymerase chain reaction and Western blotting showed concomitant
      up-regulation of insulin-like growth factor (IGF)-1, platelet-derived growth
      factor (PDGF)-B, and PDGF-receptor (R)alpha. 17beta-estradiol significantly
      inhibited SMC proliferation and intimal thickening. Similarly, estrogen
      administration completely suppressed IGF-1 mRNA (P=0.004) and protein but had no
      effect on IGF-1R. Estrogen had virtually no effect on PDGF-A mRNA or protein
      levels; however, on day 7, it inhibited PDGF-Ralpha mRNA by 74% (P=0.005) and
      protein by 67%. On day 7, it also inhibited PDGF-B mRNA expression by 36%
      (P=0.04) but had little effect on protein. PDGF-Rbeta expression was unaffected
      by estrogen. Estradiol treatment reduced immunoreactivity of IGF-1, PDGF-A, PDGF
      Ralpha, and PDGF-B in vascular lesions, whereas no changes were seen with respect
      to IGF-1R and PDGF-Rbeta. CONCLUSIONS: Our findings demonstrate that estrogen
      regulates IGF-1, PDGF-A, PDGF-B, and PDGF-Ralpha, which may be related to the
      vasculoprotective effect of estrogen, but has no effect on IGF-1R or PDGF-Rbeta.

PMID- 14724433
TI  - Donor hypertension increases graft immunogenicity and intensifies chronic changes
      in long-surviving renal allografts.
AB  - BACKGROUND: Marginal donor organs are used increasingly for transplantation. To
      define the influences of donor hypertension, we compared the behavior of kidney
      allografts from hypertensive and normotensive donors in an established rat model
      of chronic rejection. METHODS: Donor hypertension was induced by partial
      occlusion of the right renal artery with a silver clip. After 10 weeks, the left
      kidney was removed and transplanted. Normotensive animals served as controls. All
      recipients were treated with a low dose of cyclosporine for 10 days (1.5 mg/kg).
      Blood pressure and proteinuria were determined weekly four times after
      transplantation. To examine the effects of donor hypertension on late events,
      grafts (n=6/time point) were examined morphologically and by quantitative reverse
      transcriptase-polymerase chain reaction analysis at serial intervals. RESULTS:
      Recipients of kidneys from hypertensive donors developed systemic hypertension in
      contrast with normotensive controls (P<0.05). Allografts from hypertensive
      animals showed accelerated deterioration in structure and function after
      transplantation. Proteinuria became significantly elevated as early as 6 weeks
      (P<0.05) compared with controls and increased progressively thereafter (P<0.005).
      Grafts from hypertensive donors, histologically normal at the time of
      engraftment, developed significant morphologic deterioration after 12 weeks
      (P<0.01). Changes in allografts from normotensive donors remained minor. mRNA of
      proinflammatory mediators in hypertensive donor grafts (P<0.01) was up-regulated
      before transplantation and increased progressively over time (P<0.01).
      CONCLUSIONS: Donor hypertension intensifies the chronic injury associated with
      allogeneic kidney transplantation in the rat model used. This condition also
      leads to induction of recipient hypertension and may be a more important risk
      factor for chronic graft dysfunction than previously appreciated.

PMID- 14724434
TI  - The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: a
      crosscheck hypothesis.
AB  - BACKGROUND: The regulatory mechanism by which the B7 ligands (CD80 and CD86)
      direct the CD28/CD152 costimulatory pathways is unclear. This study investigated
      the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. METHODS:
      A low-responding cardiac transplant model (BALB/c-->B10.A) with possible long
      term acceptance was used. Immunocytochemical and flow cytometric analyses of the
      graft-infiltrating cells were conducted to characterize this transplant model.
      The influence of anti-CD80 and anti-CD86 treatments on the proliferation and
      interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed.
      The role of CD80 and CD86 in the induction and maintenance of the graft
      acceptance in this transplant model were also tested. RESULTS: B10.A mice could
      accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked
      the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses
      showed that CD152+ cells were predominant among the CD4+ cells infiltrating the
      100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86
      treatment significantly enhanced polyclonal proliferation and IL-2 production of
      the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance
      transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting
      undermined the established allograft tolerance. CONCLUSIONS: Both CD80 and CD86
      were essential for the induction and maintenance of the CD152-mediated allograft
      tolerance.

PMID- 14724435
TI  - The novel anti-inflammatory agent lisofylline prevents autoimmune diabetic
      recurrence after islet transplantation.
AB  - BACKGROUND: Pancreatic islet transplantation has become a promising treatment for
      type 1 diabetes. However, autoimmune reactivity destroys engrafted islets in type
      1 diabetic recipients. The authors' previous studies demonstrated that a novel
      anti-inflammatory agent, lisofylline (LSF), suppressed autoimmune reactivity and
      protected nonobese diabetic (NOD) mice from diabetes. In this study, the authors
      investigated the potential of LSF in preventing autoimmune diabetes recurrence
      after islet transplantation. METHODS: Spontaneously diabetic NOD mice received
      NOD severe combined immunodeficiency islet transplants and were treated with
      daily LSF injections at 50 mg/kg for 3 weeks. Blood glucose levels were
      monitored. Serum cytokine levels were measured at 1 and 3 weeks after
      engraftment. Nephrectomy of the islet-implanted kidney was performed in LSF
      treated recipients. Histology of islet grafts was assessed at the end of the
      study. The effect of LSF on beta-cell function was studied in vitro. RESULTS:
      Without immunosuppressants and insulin, the LSF-treated recipient mice maintained
      euglycemia significantly longer than the saline-treated recipients (mean, >65
      days in the LSF-treated group vs. 6 days in saline controls; P=0.0004). Serum
      levels of interferon-gamma were markedly reduced in LSF-treated recipients at 1
      and 3 weeks posttransplant. Diabetes recurred in the LSF-treated recipients after
      removing the islet-implanted kidneys. Immunohistochemistry showed retention of
      insulin-positive cells in the grafts of the LSF-treated recipients. LSF preserved
      beta-cell insulin secretory function in the presence of inflammatory cytokines in
      vitro. CONCLUSIONS: This study demonstrates that autoimmune diabetes recurrence
      after islet transplantation could be prevented by treatment with LSF. LSF and its
      analogues may have the potential to prevent islet autoimmune destruction in
      clinical transplantation.

PMID- 14724436
TI  - High levels of C-reactive protein after simultaneous pancreas-kidney
      transplantation predict pancreas graft-related complications and graft survival.
AB  - BACKGROUND: Although pancreas graft-related complications are frequent after
      simultaneous pancreas-kidney transplantation (SPK), there are no parameters
      predicting the risk for these complications. METHOD: A two-center retrospective
      study was performed in 97 patients who underwent SPK to investigate the peak
      serum value of c-reactive protein (CRP) during the first 72 hr after SPK in view
      of graft-related complications and graft survival. RESULTS: Mean peak CRP was
      115.6 +/- 71.5 mg/L. Mean peak CRP was higher in patients needing relaparotomy
      (n=31) (136.4 vs. 105.8 mg/L, P=0.048), especially when postoperative bleeding
      was excluded (P=0.015); in patients with graft pancreatitis (P=0.03); and in
      patients with graft loss (n=19; P<0.001) compared with patients without these
      complications. With a cut-off of peak CRP at the level of mean plus 1 SD (187.05
      mg/L), there was a significantly higher incidence of relaparotomies (P=0.01;
      bleedings excluded: P=0.003), graft pancreatitis (P=0.03), and pancreas graft
      loss (P<0.0001) in patients with high peak CRP compared with patients with low
      peak CRP. No differences were noticed with regard to rejection rate, mortality,
      and kidney graft loss. CONCLUSION: Our findings suggest that peak CRP is a
      helpful parameter in predicting pancreas graft-related complications and pancreas
      graft survival after SPK. Our results also stress the importance of early graft
      damage in pancreas transplantation.

PMID- 14724437
TI  - Ten years of international experience with liver transplantation for familial
      amyloidotic polyneuropathy: results from the Familial Amyloidotic Polyneuropathy
      World Transplant Registry.
AB  - BACKGROUND: Transthyretin (TTR) amyloidosis is a group of systemic amyloidoses
      disorders caused by an amyloidogenic TTR variant. Untreated, it slowly leads to
      severely disabling symptoms that relentlessly progress until the death of the
      patient. Because the mutant form of TTR is produced mainly in the liver,
      successful orthotopic liver transplantation (OLT) results in the elimination of
      the source of the variant TTR molecule and is presently the only known curative
      treatment. OLT in patients with familial amyloidotic polyneuropathy (FAP) was
      first performed in 1990 at the Karolinska Institute in Sweden, and because the
      results were promising other centers took up the procedure. METHODS: To gain as
      great an experience as possible regarding this treatment, the Familial
      Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) was initiated in
      1995, and this article presents the 10-year registry results. RESULTS: A total of
      54 centers in 16 countries have performed OLT for FAP, and today approximately 60
      OLTs are performed annually worldwide. During the last decade, a total of 539
      patients have undergone 579 OLTs. Patient survival is excellent (overall 5-year
      patient survival 77%) and comparable to the survival with OLT performed for other
      chronic liver disorders, but longer follow-up is needed to compare the outcome
      after OLT with the natural course of the disease. The main cause of death was
      cardiac related (39%). CONCLUSIONS: We believe that the FAPWTR has become a
      valuable tool that will help to accurately evaluate the potential risks and
      benefits of OLT in patients with FAP and promote a fruitful collaboration between
      centers engaged in this field.

PMID- 14724438
TI  - Utility of transcranial doppler ultrasonography for confirmatory diagnosis of
      brain death: two sides of the coin.
AB  - BACKGROUND: Although the clinical examination and documentation of the clinical
      signs of brain death are very uniform, there are significant differences in the
      guidelines for using technical confirmatory tests to corroborate the clinical
      signs. The current study examined the utility of transcranial Doppler
      ultrasonography (TCD) for confirmation of brain death. METHODS: After 19 patients
      were excluded from the study because of lack of bone window or because an apnea
      test could not be performed because of desaturation, 100 patients (61 patients
      with clinical brain death, and 39 control patients with Glasgow Coma Score<5)
      were included in the study. The following TCD findings were accepted as
      confirmatory of brain death when they were found bilaterally or in at least three
      different arteries for at least 3 minutes within the same examination: (1) brief
      systolic forward flow or systolic spikes and diastolic reverse flow, (2) brief
      systolic forward flow or systolic spikes and no diastolic flow, or (3) no
      demonstrable flow in a patient in whom flow had been clearly documented in a
      previous TCD examination. RESULTS: The sensitivity and specificity of the first
      TCD examination for confirmation of brain death were 70.5% and 97.4%,
      respectively. Eighteen patients with clinical brain death required repeat TCD
      examinations because of detection of forward systolo-diastolic flow or a
      diastolic to-and-fro flow pattern, which were not confirmatory for the diagnosis
      of brain death. Brain death was confirmed ultrasonographically in 12 of 18
      patients in a second examination after 12.6 +/- 8.3 hours of clinical brain
      death, in 2 patients in a third TCD examination, and in 1 patient in a fourth
      examination. Three clinically brain-dead patients had died before the diagnosis
      was confirmed by repeat TCD examinations. The sensitivity of TCD reached 100% in
      our study population after the fourth examination. CONCLUSION: The sensitivity of
      TCD is increased with repeat examinations and should be repeated in cases in
      which systolo-diastolic forward flow is demonstrated after the first TCD. TCD may
      prolong or shorten the time to declaration of brain death. The necessity of
      demonstrating cerebral circulatory arrest in patients with clinical brain death
      is debatable.

PMID- 14724439
TI  - Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation:
      relationship between viral load, EBV-specific T-cell reconstitution and rituximab
      therapy.
AB  - BACKGROUND: Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic
      hematopoietic stem-cell transplantation markedly improved with quantitative real
      time polymerase chain reaction amplification of EBV DNA and visualization of EBV
      specific CD8+ T cells with peptide-human leukocyte antigen (HLA) class I
      tetramers. We decided to combine these methods to evaluate posttransplant EBV
      reactivation and rituximab therapy. METHODS: We followed 56 patients treated with
      an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19),
      or an unrelated cord-blood transplant (n=5). EBV DNA was quantified in plasma and
      in peripheral blood mononuclear cells (PBMC). Patient CD8+ T cells were stained
      with a panel of eight tetramers. RESULTS: EBV DNA was detected in half of the
      patients, mainly in the MUD group (17/19). In 19 patients, viral DNA was detected
      only in the cellular compartment. All patients who controlled reactivation
      without rituximab and despite a viral load of greater than 500 genome equivalents
      (gEq)/150,000 PBMC mounted an EBV-specific CD8+ T-cell response in greater than
      1.4% of CD3+CD8+ T cells. Plasmatic EBV genome was found in nine patients
      preceded by a high cellular viral load. Three of these patients controlled the
      reactivation before or without the introduction of rituximab, and they all
      developed a significant and increasing EBV-specific T-cell response. Patients
      with EBV-specific T cells at the onset of reactivation controlled viral
      reactivation without rituximab. CONCLUSION: This study emphasizes the benefit of
      an early and close monitoring of EBV reactivation and CD8+-specific immune
      responses to initiate rituximab only when necessary and before the immune
      response becomes overwhelmed by the viral burden.

PMID- 14724440
TI  - Donor age affects fibrosis progression and graft survival after liver
      transplantation for hepatitis C.
AB  - BACKGROUND: The use of liver allografts from an older donor (OD) (age>50 years)
      is a widespread strategy to manage the disparity between supply and demand of
      organs for liver transplantation. This study determines the effect of OD
      allografts on fibrosis progression and graft survival after liver transplantation
      in patients with and without infection caused by hepatitis C virus (HCV).
      METHODS: All patients undergoing liver transplantation at our center from March
      1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1,
      16, and 52 weeks after transplantation and yearly thereafter. One liver
      pathologist scored all biopsy specimens for modified hepatic activity index (0
      18) and fibrosis (0-6). RESULTS: A total of 402 patients (167 with HCV and 235
      without HCV) underwent liver transplantation during the study period. Among
      patients with HCV, baseline characteristics of OD recipients were similar to
      younger donor (YD) (age<50 years) recipients. In patients with HCV, graft
      survival was shorter in OD graft recipients than in YD recipients (P<0.001). In
      patients without HCV, graft survival was independent of donor age. In patients
      with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at
      4 months and in 26% at 12 months after transplantation, compared with 8% of YD
      recipients at 4 months and 13% at 12 months (P<0.001). CONCLUSIONS: Liver
      transplantation with OD grafts is associated with rapid progression of fibrosis
      and decreased graft survival in patients with HCV, but not in patients without
      HCV. OD grafts should be considered preferentially for patients without HCV.

PMID- 14724441
TI  - Is there disparity between risk and incidence of cardiovascular disease after
      liver transplant?
AB  - BACKGROUND: Hypertension and hypercholesterolemia are recognized complications of
      liver transplantation, but whether they contribute to the development of
      cardiovascular disease is uncertain. We aimed first to determine the prevalence
      of risk factors for coronary heart disease (CHD) after liver transplantation and
      second to study the effect of liver transplantation on the predicted 10-year risk
      of developing CHD and the incidence of cardiovascular events in comparison with a
      matched local population. METHODS: Data on blood pressure, serum lipids, weight,
      diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and
      stroke were obtained retrospectively from the case notes of 181 consecutive adult
      liver transplant recipients (median follow-up 54 months). The Framingham coronary
      risk equations were used to calculate the 10-year probability of developing CHD.
      RESULTS: The prevalences of hypertension and hypercholesterolemia after
      transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD
      increased from 6.9% before transplantation to 11.5% at 1 year after
      transplantation, whereas that of a matched local population was 7%. Compared with
      a matched nontransplant population, the incidence ratios for MI and stroke were
      0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval,
      0.18-5.22), respectively. No patients died from MI or stroke. CONCLUSIONS: Liver
      transplant recipients have a high prevalence of risk factors for cardiovascular
      disease, exceeding that of the general population, and have a higher predicted
      risk of developing CHD. Despite this, there were no deaths from CHD or stroke
      during the study period.

PMID- 14724442
TI  - Predicting outcome after liver transplantation: utility of the model for end
      stage liver disease and a newly derived discrimination function.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) has been found to
      accurately predict pretransplant mortality and is a valuable system for ranking
      patients in greatest need of liver transplantation. It is unknown whether a
      higher MELD score also predicts decreased posttransplant survival. METHODS: We
      examined a cohort of patients from the United Network for Organ Sharing (UNOS)
      database for whom the critical pretransplant recipient values needed to calculate
      the MELD score were available (international normalized ratio of prothrombin
      time, total bilirubin, and creatinine). In these 2,565 patients, we analyzed
      whether the MELD score predicted graft and patient survival and length of
      posttransplant hospitalization. RESULTS: In contrast with its ability to predict
      survival in patients with chronic liver disease awaiting liver transplant, the
      MELD score was found to be poor at predicting posttransplant outcome except for
      patients with the highest 20% of MELD scores. We developed a model with four
      variables not included in MELD that had greater ability to predict 3-month
      posttransplant patient survival, with a c-statistic of 0.65, compared with 0.54
      for the pretransplant MELD score. These pretransplant variables were recipient
      age, mechanical ventilation, dialysis, and retransplantation. Recipients with any
      two of the three latter variables showed a markedly diminished posttransplant
      survival rate. CONCLUSIONS: The MELD score is a relatively poor predictor of
      posttransplant outcome. In contrast, a model based on four pretransplant
      variables (recipient age, mechanical ventilation, dialysis, and
      retransplantation) had a better ability to predict outcome. Our results support
      the use of MELD for liver allocation and indicate that statistical modeling, such
      as reported in this article, can be used to identify futile cases in which
      expected outcome is too poor to justify transplantation.

PMID- 14724443
TI  - Impact of evolving trends in recipient and donor characteristics on
      cytomegalovirus infection in liver transplant recipients.
AB  - BACKGROUND: This study determines whether the recipient and donor characteristics
      that influence the cytomegalovirus (CMV) infection rate after liver
      transplantation have changed. METHODS: The recipient and donor characteristics
      that may affect the rate of CMV infection were assessed in 232 liver transplant
      recipients at our institution during a 14-year period (1989-2003). RESULTS: Since
      1989, the age of recipients (P=0.0001) and donors (P=0.0001) has increased
      significantly. Pretransplant CMV seropositivity in recipients has decreased
      significantly (P=0.0001, 86.4% [1989-1992] to 53.7% [2000-2003]), whereas donor
      CMV seropositivity has remained unchanged (P>0.20). As a result, there has been a
      significant increase in the proportion of high-risk (CMV recipient-/donor+)
      patients (P=0.012); 10.6% of recipients from 1989 to 1992 versus 24.1% of
      recipients from 2000 to 2003 were CMV recipient-/donor+. The Child-Pugh scores of
      recipients have remained unchanged over time. However, the proportion of patients
      undergoing transplantation while being cared for in the intensive care unit has
      decreased significantly over time (P=0.0002). Despite an increase in the rate of
      CMV infection (P=0.09), the incidence of CMV disease has decreased significantly
      (P=0.0004). CONCLUSIONS: The proportion of high-risk patients (CMV recipient
      /donor+) has increased significantly over time, attributable largely to a
      declining rate of CMV seropositivity in recipients before transplantation. These
      data have implications for guiding prophylactic practices and resource use after
      liver transplantation.

PMID- 14724444
TI  - Long-term follow-up of percutaneous transhepatic balloon cholangioplasty in the
      management of biliary strictures after liver transplantation.
AB  - BACKGROUND: This study evaluated the efficacy of a protocol of initial balloon
      dilation for biliary strictures after liver transplantation. METHODS: Complete
      records from 96 patients with biliary strictures were retrospectively reviewed.
      Seventy-six patients received percutaneous transhepatic balloon cholangioplasty
      (PTBC) after initial placement of biliary drainage (percutaneous transluminal
      cholangiography [PTC]) tube. In most cases, three dilations were performed with a
      4 to 8 week interval between procedures. Follow-up ranged from 6 months to 10
      years. RESULTS: PTBC successfully treated strictures in 39 of 76 (51.3%) cases.
      Factors favoring successful PTBC included older age at transplant, shorter cold
      ischemic time, and single strictures. There were nine recurrent strictures after
      PTBC, all of which were successfully treated by nonoperative measures. The number
      of dilations performed affected both the likelihood of success and the long-term
      risk of stricture recurrence. Of the 37 PTBC failures, 14 underwent subsequent
      surgical revision. When both angiographic and surgical modalities were
      considered, treatment success was associated with first transplants, shorter cold
      ischemic time and operative time, and less intraoperative transfusion
      requirements. Factors associated with treatment failure included multiple,
      central hepatic duct, and intrahepatic strictures. PTC-tube independence was
      achieved in 51 of 76 (67%) patients using the combined approach of PTBC and
      surgery for PTBC failures. CONCLUSIONS: PTBC is an effective initial modality for
      treating posttransplant biliary strictures. Prolonged cold ischemic and operative
      times and multiple or peripheral strictures predispose to treatment failure.
      Solitary extrahepatic strictures that fail PTBC are salvageable with surgical
      revision with excellent results.

PMID- 14724445
TI  - Topical photodynamic therapy in the treatment of actinic keratoses and Bowen's
      disease in transplant recipients.
AB  - BACKGROUND: Transplant recipients (TR) have a dramatically increased risk for
      widespread epithelial neoplasms of the skin. Thus, there is a need to treat
      initial stages of these neoplasms such as actinic keratoses (AK) and Bowen's
      disease (BD) to prevent progression to invasive and potentially fatal squamous
      cell carcinoma. Topical photodynamic therapy (PDT) has been proven to be an
      effective treatment for AK and BD in immunocompetent patients, but no prospective
      trials in immunocompromised TR have been performed so far. METHODS: Twenty TR and
      20 controls with histologically confirmed AK or BD underwent either a single or
      two consecutive treatments of topical PDT in an open trial. The application of
      20% 5-aminolevulinic acid (ALA) for 5 hours was followed by illumination with 75
      J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source.
      RESULTS: The overall complete response rates in TR at 4, 12, and 48 weeks were
      0.86, 0.68, and 0.48, respectively. The cure rates in both patient groups were
      comparable at 4 weeks but were significantly lower in TR than in controls at 12
      and 48 weeks (P<0.05). Side effects included erythema, edema, and crust formation
      after illumination. Cosmetic results were excellent without scar formation or
      alterations in pigmentation. CONCLUSIONS: Topical PDT with 20% 5-ALA is an
      effective and safe treatment for AK and BD in immunosuppressed TR, with initial
      response rates comparable with those in immunocompetent patients. It is
      particularly useful in TR because of the possibility for repeated treatment of
      large lesional areas.

PMID- 14724446
TI  - Identification, cloning, and characterization of a novel rat natural killer
      receptor, RNKP30: a molecule expressed in liver allografts.
AB  - BACKGROUND: As a component of the innate immune system, natural killer (NK) cells
      may play a significant role in the early events after solid-organ
      transplantation. Activated NK cells have been shown to infiltrate allografts in
      transplant models. To better understand NK cells and the role of NK cell
      receptors in transplantation, we have cloned and begun characterizing a novel rat
      molecule, rNKp30. METHODS: RNKp30 cDNA was cloned by 5' rapid amplification of
      cDNA ends polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR from
      mononuclear cells infiltrating a rejecting liver allograft. Southern blot
      analysis was used to determine the rNKp30 gene copy number. RT-PCR and Northern
      blotting were used to examine rNKp30 RNA expression in NK cells, multiple
      tissues, and liver grafts. Immunocytochemistry, immunoprecipitation, and Western
      blot analysis with two anti-rNKp30 polyclonal antibodies, CA680 and CA1071, were
      performed. Tunicamycin and endoglycosidase treatments determined the extent of
      rNKp30 glycosylation. RESULTS: RNKp30 is homologous to human and macaque NKp30.
      It is a single copy gene with five identified single-nucleotide polymorphisms.
      RNKp30 is expressed by NK cells and is detectable as a single transcript by
      Northern blot in normal spleen, lymph node, and lung tissues. RNKp30 is a
      variably N-glycosylated cell surface molecule with a protein backbone of
      approximately 21 kDa. Elevated transcript expression of rNKp30 is detected in
      both rejected and spontaneously accepted liver allografts, but not in syngeneic
      or cyclosporine A-treated allografts. CONCLUSIONS: RNKp30 is a glycosylated
      surface NK cell receptor with limited polymorphism. This putative activation
      receptor is expressed in liver allografts and may participate in the innate
      immune response after transplantation.

PMID- 14724447
TI  - Thrombotic microangiopathy associated with combined sirolimus and tacrolimus
      immunosuppression after intestinal transplantation.
AB  - Calcineurin inhibitor-induced thrombotic microangiopathy (TMA) has been described
      in up to 14% of solid-organ transplant recipients. Sirolimus has recently been
      described in two reports in association with TMA. Sirolimus is known to
      potentiate cyclosporine-induced nephrotoxicity, but such effect has not been
      shown with tacrolimus. We report two intestinal transplant patients who developed
      TMA while on a tacrolimus and sirolimus immunosuppressive regimen. This syndrome
      appeared soon after institution of or increase in sirolimus dosage and improved
      only after this medication was discontinued.

PMID- 14724448
TI  - Retransplantation in patients with graft loss caused by polyoma virus
      nephropathy.
AB  - The characteristics and outcome in 10 patients who underwent retransplantation
      after losing their renal grafts to BK virus-associated nephropathy (BKAN) are
      described. The patients underwent retransplantation at a mean of 13.3 months
      after failure of the first graft. Nephroureterectomy of the first graft was
      performed in seven patients. Maintenance immunosuppression regimens after the
      first and second grafts were similar, consisting of a combination of a
      calcineurin inhibitor, mycophenolate mofetil, and prednisone. BKAN recurred in
      one patient 8 months after retransplantation, but stabilization of graft function
      was achieved with a decrease in immunosuppression and treatment with low-dose
      cidofovir. After a mean follow-up of 34.6 months, all patients were found to have
      good graft function with a mean creatinine of 1.5 mg/dL. From this collective
      experience from five transplant centers (although the follow-up after
      retransplantation was not extensive), it can be concluded that patients with
      graft loss caused by BKAN can safely undergo retransplantation. The risk of
      recurrence does not seem to be increased in comparison with the first graft.

PMID- 14724449
TI  - Effects of sinus surgery in patients with cystic fibrosis after lung
      transplantation: a 10-year experience.
AB  - Chronic infectious rhinosinusitis with Pseudomonas aeruginosa is common in cystic
      fibrosis and may result in allograft infection after lung transplantation. Sinus
      surgery followed by nasal care may reduce these adverse effects. Sinus surgery
      was performed in 37 patients with cystic fibrosis after transplantation.
      Bacteriology of sinus aspirates (n=771) and bronchoalveolar lavage (BAL) (n=256)
      was correlated with clinical data. Sinus surgery was successful in 54% and
      partially successful in 27% of patients. A significant correlation between
      negative sinus aspirates and negative BAL and between positive sinus aspirates
      and positive BAL (P<0.0001) was found. Successful sinus management led to a lower
      incidence of tracheobronchitis and pneumonia (P=0.009) and a trend toward a lower
      incidence of bronchiolitis obliterans syndrome (P=0.23). Sinus surgery followed
      by daily nasal douching may control posttransplant lower airway colonization and
      infection. In the long term, this concept may lead to less bronchiolitis
      obliterans syndrome by decreasing bronchiolar inflammation.

PMID- 14724450
TI  - Liver transplantation using an organ donor with HELLP syndrome.
AB  - BACKGROUND: The shortage of organs for liver transplantation has forced
      transplant centers to expand the donor pool by using donors traditionally labeled
      as marginal. One such example is liver transplantation using a donor with HELLP
      syndrome (hemolysis, elevated liver enzymes, and low platelets), a disorder of
      late pregnancy that involves the liver as one of the target organs. METHODS: Two
      patients who died from complications of HELLP syndrome were evaluated for
      attempted multi-organ procurement. Donor characteristics, gross and microscopic
      liver findings, and procurement and transplant outcomes were reviewed. RESULTS:
      One of the liver allografts was successfully transplanted; the other was not
      procured because of poor macroscopic appearance. CONCLUSION: It is possible to
      successfully transplant the liver from a donor that succumbs to HELLP syndrome,
      provided there is adequate recovery of liver function before procurement.

PMID- 14724451
TI  - Subcutaneous black fungus (phaeohyphomycosis) infection in renal transplant
      recipients:three cases.
AB  - We describe three cases of subcutaneous phaeohyphomycosis developing in the lower
      limbs of renal transplant recipients shortly after transplantation. Each case
      presented with dark-colored nodules that subsequently ulcerated. Histopathologic
      examination revealed dematiaceous fungal hyphae with a surrounding granulomatous
      reaction. The fungi were subsequently identified as Alternaria alternatum in two
      cases and Phialophora richardsiae in one case. In one case, the lesions resolved
      during a prolonged (6-month) course of itraconazole without the requirement for
      surgical excision. In the other two cases, combined medical and surgical
      treatment resulted in cure. A review of the literature on phaeohyphomycosis is
      presented.

PMID- 14724452
TI  - The development of new density gradient media for purifying human islets and
      islet-quality assessments.
AB  - Successful islet transplantation is dependent on the quality and quantity of
      islets infused. Islets are purified on density gradients, but procedures
      currently used have limited capacity for pancreatic digests, islet yield, and
      viability. We aimed to improve islet purification with a modified gradient
      medium. Biocoll was diluted in University of Wisconsin solution to create linear
      density gradients of 1.065 to 1.095 g/mL. Properties of islets purified from 22
      human pancreas digests with modified medium were compared with 15 preparations
      using standard medium. The modification increased the capacity of gradients for
      pancreatic digests from 20 to 60 mL, islet yield increased from 218,000 to
      435,318 per isolation, and viability increased from 65.4% to 92.1%. Islet
      fractions contained greater than 95% of recovered insulin. Islets showed good
      physiologic responses to secretagogues and restored normoglycemia in
      streptozotocin-induced diabetic severe combined immunodeficiency disease mice.
      The new medium enhances yield, purity, and viability of human islet preparations
      for clinical islet transplantation.

PMID- 14724453
TI  - Renal cell carcinoma of the grafted kidney: how to improve screening and graft
      tracking.
AB  - Renal cell carcinoma of transplanted kidneys is rare. We report three such cases
      among 1,250 kidney grafts that were performed or followed from 1968 to 2002. A
      strategy to diagnose these lesions is needed because of their rarity, late
      detection, and therapeutic repercussions. At the least, the strategy should
      include annual ultrasonography of the graft throughout its lifespan. Because the
      risk of tumor development in another organ from the same donor is not negligible,
      a national registry should be established to rapidly alert graft recipients with
      the same donor and other transplantation centers about the risk of graft tumors.

PMID- 14724455
TI  - A bridge between hearts: mutual organ donation by Arabs and Jews in Israel.
AB  - BACKGROUND: The availability of organ transplants depends largely on the will of
      the donor families. Given the current state of affairs in Israel, the authors
      evaluated the stance of Jews and Arabs toward mutual organ donations. METHODS:
      Between October 1997 and December 1999, there were 4.8 million Jews and 1.09
      million Arabs living in Israel. Data gathered from 22 general hospitals for this
      period yielded 373 potential organ donors and 171 families (45.8%) that consented
      to the procedure. Actual donation was obtained from 157 patients. The authors
      examined the characteristics of the potential organ donors and organ recipients
      and the reasons (religious and nonreligious) for familial consent or refusal.
      Donation made since onset of the Intifada (armed Palestinian resistance) was also
      reviewed to determine whether any changes took place. RESULTS: Consent was
      obtained from 48.9% of the Jewish families approached, 30.7% of the Muslim Arabs,
      and 66.6% of the Christian Arabs. For the whole sample, altruism was the main
      reason for consenting. The percentages of Arabs and Jews (per population) on the
      waiting list for a heart (Jews, 90%; Arabs, 10%) or liver (Jews, 78.66%; Arabs,
      21.34%) and who received a heart (Jews, 90%; Arabs, 10%) or liver (Jews, 78.36%;
      Arabs, 21.64%) were similar. There were relatively more Arab recipients of kidney
      transplants (waiting list, 11%; recipients, 18.6%) because of the higher
      percentage of children in the Arab group who were given priority. Since September
      2000 (start of the Intifada), there has been a trend toward an increasing rate of
      refusal to donate among Arabs (consent obtained in 52.9% of Jewish families
      approached vs. 27.9% of the Muslim Arabs), mainly because of fear of rejection by
      the community for cooperating with Jews. CONCLUSIONS: The rate of organ donations
      among Arabs and Jews in Israel is proportional to their representation in the
      general population. The main reason for donating organs is altruism. Apparently,
      altruism cuts across the boundaries of religion and ethnic groups, even in a
      country where conflict prevails. We trust that progress in the international
      arena will bring the current cycle of violence to an end and allow humanitarian
      values to take preference over politics.

PMID- 14724457
TI  - Increasing organ transplantation--fairly.
AB  - Ten to 30 times as many people die as a result of end-organ failure than are
      fortunate enough to undergo transplantation. To date, efforts to increase the
      donor pool or establish an alternative to transplant have failed. The authors'
      goal was to define a revision to the transplant system that can use innate human
      motivators to lead to an increase in organ donation. People are motivated more by
      self-interest than by altruism. To increase organ donation, the incentive needs
      to be aligned with self-interests. Therefore, the authors propose that the
      priority to receive a transplant should be based on prior willingness to be a
      donor: to get, you have to be willing to give. This would replace the "time on
      list" as a key variable in determining priority and waiting time. The commitment
      to the system of transplant--being a willing donor--is the fairest way to
      prioritize recipient status. Such a system will encourage more donation as people
      on the donor list start to receive transplants themselves, especially when the
      transplant takes place quickly, before risk becomes excessive.

PMID- 14724458
TI  - Incentives to promote organ donation.
AB  - The worldwide shortage of organs has led to the development of incentives to
      promote organ donation. These incentives vary widely in nature ranging from
      financial remuneration to preferential access to conditional donation. Such
      strategies to increase organ donation present a variety of ethical dilemmas
      challenging traditional concepts of justice and equity of access. In addition,
      there are legal and logistic considerations that must be discussed. The case is
      made that schemes using incentives to promote organ donation must meet the
      requirements of society for justice, equity of access, and avoidance of racial or
      other bias.

PMID- 14724459
TI  - Toward calcineurin antagonist minimization.

PMID- 14724461
TI  - Overview of anemia and blood management in critical care.

PMID- 14724462
TI  - Red blood cell physiology in critical illness.
AB  - OBJECTIVE: Reduction in red blood cell mass, as well as structural and functional
      alterations of erythrocytes, occurs in critical illness. This review discusses
      these changes in red blood cell physiology, emphasizing the pathogenesis of
      anemia in intensive care unit patients. DATA SOURCE: Studies published in
      biomedical journals. DATA SYNTHESIS AND CONCLUSION: Anemia in intensive care unit
      patients resembles the anemia of chronic disease, being characterized by
      diminished erythropoietin production relative to decreased hematocrit, altered
      iron metabolism, and impaired proliferation and differentiation of erythroid
      progenitors in the bone marrow. Inflammatory mediators play a major role in the
      development of insufficient erythropoiesis and altered iron metabolism.
      Furthermore, a proinflammatory milieu promotes structural and functional
      alterations of erythrocytes, impairing their deformability and possibly impairing
      microvascular perfusion. Collectively, these changes in red blood cell physiology
      can impair oxygen transport to tissues and, thereby, might contribute to the
      development of multiple organ failure in critical illness.

PMID- 14724463
TI  - Oxygen delivery.

PMID- 14724464
TI  - Transfusion practice in the critically ill.
AB  - BACKGROUND: Anemia in the critically ill patient population is common. This
      anemia of critical illness is a distinct clinical entity characterized by blunted
      erythropoietin production and abnormalities in iron metabolism identical to what
      is commonly referred to as the anemia of chronic disease. FINDINGS: As a result
      of this anemia, critically ill patients receive an extraordinarily large number
      of blood transfusions. Between 40% and 50% of all patients admitted to intensive
      care units receive at least one red blood cell unit, and the average is close to
      five red blood cell units during their intensive care unit stay. There is little
      evidence that "routine" transfusion of stored allogeneic red blood cells is
      beneficial for critically ill patients. Most critically ill patients can tolerate
      hemoglobin levels as low as 7 mg/dL, so a more conservative approach to red blood
      cell transfusion is warranted. CONCLUSION: Practice strategies should be directed
      toward a reduction of blood loss (phlebotomy) and a decrease in the transfusion
      threshold in critically ill patients.

PMID- 14724465
TI  - Anemia and red cell transfusion in critically ill patients.

PMID- 14724466
TI  - Risks of blood transfusion.
AB  - OBJECTIVE: To review the current status of risks of blood transfusion. DATA
      SOURCES, EXTRACTIONS, AND SYNTHESIS: English-speaking literature, literature
      search using key works, human data, and follow-up with key bibliographic
      citations. CONCLUSIONS: Substantial advances have been achieved in blood safety
      during the last 20 yrs, particularly for transfusion-transmitted viral
      infections. Currently, the most serious known risks from blood transfusion are
      administrative error (leading to ABO-incompatible blood transfusion), transfusion
      related acute lung injury, and bacterial contamination in platelet products.
      Emerging pathogens, such as West Nile virus infection emphasize the need for
      implementation of proactive strategies, such as pathogen inactivation
      technologies, as well as reactive strategies, such as nucleic acid testing, to
      ensure continued advances in blood safety.

PMID- 14724467
TI  - Effects of storage on efficacy of red cell transfusion: when is it not safe?
AB  - OBJECTIVE: To review the literature on red blood cell storage and its
      relationship to the efficacy of transfusion. RESULTS: Well-documented changes
      occur to the red blood cell product during ex vivo storage. These changes include
      a reduction in red blood cell deformability, altered red blood cell adhesiveness
      and aggregability, and a reduction in 2,3-diphosphoglycerate and ATP. Bioactive
      compounds with proinflammatory effects also accumulate in the storage medium.
      These changes reduce posttransfusion viability of red blood cells. The clinical
      effects beyond posttransfusion viability are uncertain, but a growing body of
      evidence suggests that the storage lesion may reduce tissue oxygen availability,
      have proinflammatory and immunomodulatory effects, and influence morbidity and
      mortality. There are no published randomized, control trials examining the effect
      of storage duration on morbidity and mortality. Leukoreduction improves the
      quality of stored red blood cell products and in some studies has been shown to
      reduce morbidity and mortality. CONCLUSION: Although storage duration influences
      the quality of red blood cell product, there is currently insufficient evidence
      to advocate shorter storage periods for red blood cell products.

PMID- 14724468
TI  - Hemoglobin solutions.
AB  - OBJECTIVE: To review current knowledge about cell-free hemoglobin solutions. DATA
      SOURCE: A computerized MEDLINE search was used to retrieve all studies concerning
      cell-free hemoglobin solutions from 1990 to 2003. The reference lists of all
      available review articles and primary studies were also reviewed to identify
      references not identified in the computerized search. STUDY SELECTION: All
      clinical and experimental studies involving cell-free hemoglobin solutions were
      included. DATA EXTRACTION: From the selected studies, information was obtained
      regarding the experimental model or the study population in which cell-free
      hemoglobin solutions were investigated, the type of cell-free hemoglobin solution
      used, their deleterious or beneficial effects, and their possible indications.
      DATA SYNTHESIS: In many studies, hemoglobin solutions were considered as
      efficient resuscitative agents and good alternatives to red blood cell
      transfusion, owing to their marked vasopressor effect, coupled with their
      capacity to improve the microcirculation and rapidly restore metabolic
      parameters. The main problems identified include excessive systemic
      vasoconstriction and oxidative damage. Initial enthusiasm in the development of
      hemoglobin solutions has been tempered recently by the negative results of a U.S.
      multicenter trial studying the early infusion of diaspirin cross-linked
      hemoglobin in trauma patients. Nevertheless, the properties of diaspirin cross
      linked hemoglobin (and particularly the strong vasopressor effects) cannot be
      attributed to all hemoglobin solutions, and results of new clinical studies are
      eagerly awaited to evaluate the potential benefit of such solutions in the
      management of trauma patients. CONCLUSIONS: Today, we are aware of the effects of
      the first generation of blood substitutes. Further research is ongoing into newer
      solutions. One area of interest is the development of new molecular structures to
      decrease nitric oxide binding, thus minimizing any adverse events and maximizing
      potential benefits. Nevertheless, possible adverse effects need to be carefully
      evaluated before these agents can be widely administered.

PMID- 14724469
TI  - Surgery without blood.
AB  - OBJECTIVE: The principle aim of "bloodless surgery" is to minimize blood loss and
      to reduce or eliminate exposure to allogeneic blood transfusion. The risks
      associated with blood transfusions have been well documented, and it is the goal
      of bloodless surgery centers to avoid complications and unnecessary use of blood.
      Blood transfusion is a significant adjunct to perioperative resuscitation.
      However, we aim to elucidate different approaches to minimizing blood loss and
      avoiding transfusion. DESIGN: In this document, we review the background and
      current status of bloodless surgery centers and then the different approaches to
      achieve the program goals. FINDINGS: There is no one single universal blood
      conservation strategy that is applicable to all patients and populations. Factors
      such as preexisting disease will alter the approach; however, it is the ability
      of any program to form a comprehensive strategy for blood conservation that is
      integral to the success of any such program. CONCLUSION: The success of a
      bloodless surgery program requires both teamwork and careful cooperation between
      the blood bank, pharmacy, administration, hematologists, surgeon, and
      anesthesiologist to ensure that the goals of minimizing blood loss and avoiding
      transfusion are met.

PMID- 14724470
TI  - Blood conservation in the intensive care unit.
AB  - OBJECTIVE: To describe blood conservation strategies for critically ill patients.
      DATA SOURCES: By using a predefined strategy, we searched the electronic
      databases of Medline, EMBASE, CINAHL, the Cochrane database of systematic
      reviews, Cochrane central register of controlled trials, ACP Journal Club,
      Database of abstracts of reviews and effects, and HealthSTAR for descriptions and
      evaluations of strategies of blood conservation among critically ill patients.
      DATA SUMMARY: A number of blood conservation strategies have been used to prevent
      or treat anemia among critically ill patients. These include restrictive
      diagnostic phlebotomy using small-volume or pediatric phlebotomy tubes, point-of
      care and inline bedside microanalysis, minimization of diagnostic sample waste,
      minimization of routine multiple daily phlebotomies, red blood cell salvage and
      antifibrinolytic agents for bleeding patients, consideration of removal of
      central venous and arterial catheters when no longer required for physiologic
      monitoring, threshold-based transfusion policy, and healthcare professional
      education. CONCLUSIONS: There are many strategies of blood conservation for
      critically ill patients. The effects of these strategies on phlebotomy volumes,
      hemoglobin and hematocrit levels, transfusion requirements, clinical outcomes, as
      well as intensive care unit and laboratory resources and costs should be further
      evaluated.

PMID- 14724471
TI  - "A wake up call for corporate America".

PMID- 14724472
TI  - Assessing the burden of disease among an employed population: implications for
      employer-sponsored prevention programs.
AB  - Escalating healthcare costs have led employers to identify ways to assess the
      actual burden of disease among their employees. One such measure is the use of
      disability-adjusted life-years (DALYs). DALYs were calculated for the General
      Motors (GM) population for 1994 through 1998 using data from GM's Mortality
      Registry, published life tables, and age- and sex-specific disease incidence and
      disability data from the U.S. Burden of Disease Study. Chronic diseases accounted
      for 45% (245,844 of 540,450) of total DALYs lost. Ischemic heart disease, stroke,
      lung cancer, and chronic obstructive pulmonary disease led the list for both men
      and women and accounted for 39% and 31%, respectively, of the top 10 DALYs lost.
      Disease burden among employees could be reduced through targeted interventions
      aimed at the risk factors associated with the leading causes of DALYs.

PMID- 14724473
TI  - An estimate of the U.S. Government's undercount of nonfatal occupational
      injuries.
AB  - Debate surrounds the size of the underestimate of nonfatal occupational injuries
      produced by the U.S. Bureau of Labor Statistics (BLS). We developed models that
      separated categories of injuries: BLS Annual Survey, federal government,
      agriculture, state and local government, self-employed outside agriculture, and
      all other. The models generated varying estimates depending on the assumptions
      for each category pertaining to job risks and amount of underreporting. We
      offered justification for the assumptions based on published studies as well as
      our own analyses of BLS data. The models suggested the Annual Survey missed from
      0% to 70% of the number of injuries (from private firms, excluding the self
      employed) it was designed to capture. However, when we included firms and
      governments the Annual Survey was not designed to capture, and considered
      reasonable assumptions regarding underreporting, we estimated the BLS missed
      between 33% and 69% of all injuries. We concluded that there was substantial
      undercapture in the BLS Annual Survey, some due to the excluded categories of
      government workers and the self-employed, as well as some due to underreporting.

PMID- 14724474
TI  - The association between work performance and physical activity, cardiorespiratory
      fitness, and obesity.
AB  - The purpose of this study was to test the association between lifestyle-related
      modifiable health risks (physical activity, cardiorespiratory fitness, and
      obesity) and work performance. Data were obtained from 683 workers. Dependent
      variables included number of work loss days, quantity and quality of work
      performed, overall job performance, extra effort exerted, and interpersonal
      relationships. Results indicated that higher levels of physical activity related
      to reduced decrements in quality of work performed and overall job performance;
      higher cardiorespiratory fitness related to reduced decrements in quantity of
      work performed, and a reduction in extra effort exerted to perform the work;
      obesity related to more difficulty in getting along with coworkers; severe
      obesity related to a higher number of work loss days. It is concluded that
      lifestyle-related modifiable health risk factors significantly impact employee
      work performance.

PMID- 14724475
TI  - Autonomous growth of committed hematopoietic progenitors from peripheral blood of
      workers exposed to low levels of benzene.
AB  - We investigated whether exposure to low levels of benzene (geometric mean of
      exposures = 0.28-0.41 parts per million) results in perturbations of the
      hemopoietic system found in patients with myeloproliferative diseases. Erythroid
      (BFU-E) and granulocyte-monocyte (CFU-GM) colonies from peripheral blood were
      grown in methylcellulose with and without the addition of cytokines
      (erythropoietin and granulocyte-stimulating factor). Colony growth from 17
      workers exposed to low levels of benzene was compared with 20 healthy control
      subjects. Exposed workers had significantly increased growth of autonomous BFU-E
      and unstimulated CFU-GM when compared with the control subjects. Unexposed
      smokers had increased colony growth without the addition of cytokines. Colony
      growth was not significantly different between the groups after the addition of
      cytokines. Workers exposed to low concentrations of benzene and unexposed smokers
      have increased cytokine-independent hematopoiesis.

PMID- 14724476
TI  - Effects of coexposure to noise and mixture of organic solvents on hearing in
      dockyard workers.
AB  - Questionnaire and audiometric data of 701 dockyard workers (517 noise and organic
      solvent mixture-exposed and 184 noise-only-exposed) were referred to 205 control
      subjects not exposed to either noise or solvents. The odds ratio (OR) of hearing
      loss was significantly increased by approximately 3 times in the noise-only group
      and by almost 5 times in the noise and solvent group. A moderate effect of
      solvent ototoxicity, in addition to noise, was observed on hearing threshold at a
      frequency 8 kHz. ORs for hearing loss were 1.12 for each increment of 1 year of
      age, 1.07 for every decibel of lifetime noise exposure (dB-A), and 1.004 for each
      increment of the index of lifetime exposure to solvents. The results suggest an
      additive damaging effect of coexposure to noise and organic solvents to the
      auditory organ.

PMID- 14724477
TI  - Prevention pathways: application of the critical path methodology in occupational
      health services.
AB  - Occupational health services face important changes as a result of changes in
      work environment, changing health and safety concepts, and legislation. To ensure
      good quality at a good price, it is important to control the processes in
      occupational health services. The concept of "prevention pathways" is presented
      for the management of occupational health services. The model is based on the
      critical pathway concept. The approach is illustrated by means of a case study
      performed in a Belgian occupational health service. A prevention pathway for the
      evaluation of chemical risks at the workplace was constructed. The prevention
      pathway methodology revealed inefficiencies and quality problems in the current
      practice of chemical risk assessment and biomonitoring. The case shows how
      prevention pathways can be used to pilot the members of a multidisciplinary team
      by focusing on a specific occupational risk.

PMID- 14724478
TI  - Productivity cost benefit to employers of treating migraine with rizatriptan: a
      specific worksite analysis and model.
AB  - Employers in the United States might not be aware of the productivity costs of
      migraine or the extent to which those costs can be reduced by optimal treatment.
      An economic model was developed to enable employers to estimate the productivity
      costs of migraine to their company and the savings that will accrue if those
      patients who suffer from migraine are treated with rizatriptan. Analyses were run
      for both a major financial services corporation and a representative U.S.
      company. The major financial services corporation, with 87,821 employees, is
      projected to lose 538 person-years annually, at an estimated cost of 23.8 million
      dollars. A representative U.S. company with 10,000 employees is projected to lose
      46.0 person-years of productive effort annually as a result of migraine, valued
      at approximately 1.94 million dollars. The value of the annual work loss avoided
      if migraine is treated with rizatriptan is projected at 10.3 million dollars for
      the financial services corporation and 841,000 dollars for the representative
      U.S. company. There is a substantial productivity cost burden of migraine from a
      U.S. employer perspective. These productivity costs can be reduced significantly
      by treating migraine headaches with rizatriptan.

PMID- 14724479
TI  - Historical cohort study of U.S. man-made vitreous fiber production workers IX:
      summary of 1992 mortality follow up and analysis of respiratory system cancer
      among female workers.
AB  - We report the 1946-1992 mortality experience of 4008 females employed in any of
      10 U.S. fiberglass manufacturing plants between 1945 and 1978 relative to
      external population rates. We also examine respiratory system cancer (RSC)
      mortality as a function of estimated exposure to respirable fibers (RFib),
      formaldehyde (FOR), silica, phenolics, urea, and other agents based on internal
      cohort comparisons. No statistically significantly elevated standardized
      mortality ratios were observed for all-cause mortality (930 deaths), any of the
      25 nonmalignant causes considered, all malignant neoplasms (266 deaths), or any
      of the 27 malignant causes considered. Internal cohort comparisons revealed no
      significant positive associations between RSC mortality (53 cases) and exposure
      to RFib, FOR, or any of the other agents considered, although exposure levels
      were generally low. Some demographic subgroups appear to be at relatively
      increased risk of RSC.

PMID- 14724480
TI  - Risk factors for recurrent episodes of care and work disability: case of low back
      pain.
AB  - Recurrences of injuries are common and have significant socioeconomic
      consequences; it is important to identify associated risk factors as potential
      opportunities for prevention. This study was conducted to identify risk factors
      for low back pain (LBP) recurrence and the extent that variation in recurrence
      definition impacts identified risk factors. Patients with new claims for LBP
      reported in New Hampshire to a workers' compensation provider were selected (n =
      2023) with a minimum of 3-year follow up. Alternative definitions of recurrence
      included a new episode of medical care and a new episode of lost work time (work
      disability). Risk factors better predicted disability-based than treatment-based
      recurrence. Longer durations of the initial episode of care or work disability
      were the most powerful predictors of recurrence, implying that shorter episodes
      of care and early return to work contribute to better outcomes.

PMID- 14724481
TI  - Clinicians' knowledge, attitudes, and concerns regarding bioterrorism after a
      brief educational program.
AB  - We conducted this study to determine the knowledge, attitudes, and intended
      behaviors of New York City clinicians regarding bioterrorism-related diseases
      after a brief educational program. Data on clinicians' knowledge and attitudes
      toward bioterrorism and related diseases were collected using a self-administered
      questionnaire following a 3.5-hour educational program. Participants (n = 310,
      82% response rate) reported increased confidence in recognizing symptoms of
      bioterrorism-related diseases (89%), in addressing patients' bioterrorism
      concerns (83%), and ability to treat bioterrorism victims (75%). Despite a high
      level of confidence in the efficacy of infection control precautions,
      participants' knowledge scores regarding safe work practices suggest that
      additional education is warranted. Educational programs are useful in enhancing
      the public health response to bioterrorism and its consequences.

PMID- 14724482
TI  - Cancer incidence among members of the Norwegian trade union of insulation
      workers.
AB  - Insulation work has been described as an occupation with high exposure to
      asbestos. A cohort of members of the Norwegian Trade Union of Insulation Workers
      (n = 1116), hired between 1930 and 1975, was established. During 2002, the cohort
      was linked to the Cancer Registry of Norway. The standardized incidence ratio
      (SIR) of pleural mesothelioma was 12.9 (95% confidence interval [CI] = 6.0-24.6).
      Two cases with peritoneal mesotheliomas were found (SIR, 14.8; 95% CI = 1.8
      53.4). The SIR of lung cancer was 3.0 (95% CI = 2.3-3.8). Four cases of lung
      cancer were observed among cork workers without any exposure to asbestos, but to
      cork dust and tar smoke (SIR, 5.3; 95% CI = 1.5-13.6). Our study showed a high
      risk of mesothelioma and an elevated risk of lung cancer among members of the
      Trade Union of Insulation Workers.

PMID- 14724483
TI  - Laser eustachian tuboplasty.
AB  - OBJECTIVES: Surgery on the eustachian tube for chronic eustachian tube
      dysfunction has been previously directed toward the bony isthmus and failed to
      produce lasting results. Dynamic video analysis demonstrates pathophysiology in
      the tubal cartilaginous portion. This study investigated a new endoluminal
      procedure that focused on the cartilaginous eustachian tube. STUDY DESIGN:
      Prospective surgical trial. SETTING: Tertiary care private practice and
      outpatient surgical center. PATIENTS: One hundred eight eustachian tubes with
      intractable eustachian tube dysfunction (middle ear atelectasis or effusion) in
      56 patients underwent laser eustachian tuboplasty by the first author (O. B. K.)
      since 1997. INTERVENTION: Dynamic video analyses of eustachian tube function were
      performed perioperatively. Laser eustachian tuboplasties were performed
      unilaterally or bilaterally under general anesthesia through a combined
      endoscopic nasal and transoral approach to the eustachian tube nasopharyngeal
      orifice. Carbon dioxide or 980-nm diode laser vaporization of mucosa and
      cartilage from the luminal posterior wall was accomplished until adequately
      dilation was achieved and the tube was packed. A laser myringotomy for temporary
      middle ear aeration while the eustachian tube was packed was also performed
      during surgery. MAIN OUTCOME MEASURES: There were two outcome measures: 1) the
      presence or absence of middle ear effusion or tympanic membrane atelectasis and
      2) impedance tympanometry. In addition, dynamic videos were examined to rate the
      degree of visible opening of the tubal valve and effects on mucosal edema and
      muscular movements. RESULTS: Seventy-four (68.51%) ears achieved normal middle
      ear aeration at 1 year, 70 (71.42%) at 2 years, and 60 (65.21%) at greater than
      or equal to 3 years. There were no intraoperative complications. Postoperative
      complications were limited to minimal peritubal synechia in nine (8.33%) tubes
      and epistaxis in one (0.9%) tubes. Seven (6.48%) ears failed treatment and
      required tympanostomy tubes. CONCLUSION: Laser eustachian tuboplasty is a new
      procedure that has demonstrated early promise in correcting intractable
      eustachian tube dysfunction with few complications. Further studies will be
      necessary to reproduce the results and establish the role of laser eustachian
      tuboplasty in the management of chronic intractable eustachian tube dysfunction.

PMID- 14724484
TI  - The efficacy of Burow's solution as an ear preparation for the treatment of
      chronic ear infections.
AB  - OBJECTIVE: To determine the efficacy of Burow's solution as an otologic
      preparation for the treatment of chronic ear infection. STUDY DESIGN: Two studies
      were included: 1) a prospective clinical study and 2) a laboratory study on
      antibacterial and antifungal effects. SETTING: A private otology practice and a
      laboratory study. PATIENTS: Fifty-eight patients with refractory otorrhea.
      INTERVENTION: Diagnosis by otoscopy, audiometry, and bacteriology. METHODS:
      Burow's solution was mixed in solutions with four organisms: methicillin
      resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae,
      Candida albicans, and Aspergillus. Soon after Burow's solution was mixed in the
      solutions with organisms, and 5, 10, and 20 minutes thereafter, the mixtures were
      cultured on agars. The numbers of the bacterial or fungal colonies were counted
      to evaluate the effect of Burow's solution. MAIN OUTCOME MEASURES: Changes in the
      clinical findings of the ears, the symptom of otorrhea, and side effects were
      assessed. RESULTS: Thirty-five (70%) of the 50 ears assessed were "cured" and 10
      (20%) ears assessed were "improved." No significant side effect was observed.
      Regarding the laboratory study, the four organisms disappeared within 20 minutes
      after Burow's solution was mixed. CONCLUSION: Burow's solution was considered to
      be an effective otologic preparation.

PMID- 14724485
TI  - Eustachian tube gland changes in acute otitis media.
AB  - OBJECTIVES: To investigate the histomorphologic impact of acute otitis media on
      the subepithelial glands of the eustachian tube. Previous investigations have
      shown an increase of eustachian tube goblet cell density during and up to at
      least 6 months after acute otitis media. STUDY DESIGN: Longitudinal study in an
      experimental animal model of acute otitis media caused by Streptococcus
      pneumoniae. METHODS: Bacterial middle ear challenge, after which the animals were
      killed, in groups of five rats on Days 4, 8, 16, 90, and 180. Dissection and
      preparation of the eustachian tube and adjacent structures, followed by serial
      transverse sectioning, periodic acid-Schiff/alcian blue staining, and
      qualitative/quantitative morphometric light-microscopic investigations of the
      histomorphology of the eustachian tube glands, in particular, the stainability,
      composition, volume, and number of gland acini. RESULTS: The volume of the
      eustachian tube glands progressed to peak 16 days after inoculation, followed by
      a gradual normalization. The volume was still increased 3 months after the acute
      infection but completely normalized after 6 months. The increase was primarily
      due to hypertrophy of the mucous gland components, as the serous gland component
      volume and number of gland acini was unchanged. The periodic acid-Schiff/alcian
      blue staining of the mucous gland acini changed temporarily during the acute
      infection, indicating changes in mucus glycoprotein composition, from neutral to
      acidic/sulfated. CONCLUSION: The volume of the eustachian tube glands increases
      during and up to at least 3 months after acute otitis media, primarily because of
      hypertrophy of the mucous gland components. This may compromise tubal ventilatory
      and drainage function.

PMID- 14724487
TI  - The use of demineralized bone matrix for mastoid cavity obliteration.
AB  - OBJECTIVE: To evaluate the use of demineralized bone matrix as a graft material
      for mastoid cavity obliteration in the treatment and prevention of problematic
      mastoid cavities. STUDY DESIGN: The study is a retrospective review of patients
      identified using a computerized otology database. SETTING: Tertiary care referral
      center. PATIENTS: Patients were included in this study if they underwent mastoid
      obliteration using demineralized bone matrix. INTERVENTION: Mastoid obliteration
      was performed for revision of a problematic mastoid cavity (n = 8) or primarily
      after canal wall down mastoidectomy for recurrent cholesteatoma (n = 3). MAIN
      OUTCOME MEASURES: Data were collected to evaluate the ability to achieve a dry
      ear canal. Postoperative healing time and hearing results were also assessed.
      RESULTS: A dry ear canal was achieved in all patients with a follow-up of 6 to 20
      months (average, 14.5 mo). Eight patients (73%) had a well-healed, dry ear canal
      by their first postoperative visit (9 wk). One patient required 12.5 weeks to
      heal. Two patients (18%) had more prolonged granulation at the ear canal
      incision, which resolved in 17 and 28 weeks, respectively. The average
      preoperative pure-tone average air-bone gap was 47 +/- 14.9 dB (mean +/- SD),
      compared with postoperative values of 27.6 +/- 12.8 dB (p = 0.0033; paired t
      test). This represents an average pure-tone average air-bone gap closure of 20
      dB. CONCLUSION: The use of demineralized bone matrix as a graft extender in
      mastoid obliteration allowed creation of a dry, smooth-contoured canal in all
      patients studied. A significant improvement in hearing was also obtained.
      Demineralized bone matrix is an acceptable graft alternative for mastoid
      obliteration.

PMID- 14724486
TI  - Mastoid obliteration with hydroxyapatite cement: the Ipswich experience.
AB  - OBJECTIVE: This article reports the outcomes of a series of patients who
      underwent obliteration of the mastoid cavity using hydroxyapatite cement. A
      comparison is made with a group of patients who underwent similar surgery in the
      same period using hydroxyapatite granules. STUDY DESIGN: Nonrandomized
      observational analysis. SETTING: Tertiary otology unit. PATIENTS AND
      INTERVENTIONS: All patients requiring mastoid surgery and primary obliteration or
      revision mastoid surgery and obliteration. MAIN OUTCOME MEASURES: Dry cavity with
      full epithelialization and good tolerance to swimming at 1 year postoperatively.
      RESULTS: In four of eight patients who had obliteration using hydroxyapatite
      cement, there was infection of the obliteration site, requiring revision. All of
      the patients who had obliteration with hydroxyapatite granules had dry and well
      epithelialized mastoid cavities at 1-year follow-up, with ears that tolerated
      swimming. CONCLUSION: The use of hydroxyapatite cement is not recommended in
      mastoid obliteration surgery.

PMID- 14724488
TI  - Langerhans' cell histiocytosis of the labyrinth in adults.
AB  - OBJECTIVE: To describe and analyze three unusual cases of Langerhans' cell
      histiocytosis of the temporal bone in adults. STUDY DESIGN: Retrospective case
      review. SETTING: A tertiary referral center. PATIENTS: Three adult patients with
      progressive sensorineural or mixed hearing loss, vertigo, and tinnitus as
      presenting symptoms of Langerhans' cell histiocytosis of the temporal bone.
      INTERVENTION: Patients were evaluated by means of computed tomography and
      magnetic resonance imaging. All patients underwent complete surgical excision of
      the lesion via a transmastoid approach, extended to a translabyrinthine approach
      in one case. One patient with a multifocal disease underwent excision of a
      mandibular lesion 1 year later, followed-up by chemotherapy. RESULTS: The
      Langerhans' cell histiocytosis was located adjacent to or within the area of the
      endolymphatic sac region in all cases. The middle ear was spared. Hearing
      function was preserved in the two patients who had serviceable hearing
      preoperatively. No complication occurred. CONCLUSION: Langerhans' cell
      histiocytosis of the temporal bone is centered on or adjacent to the
      endolymphatic sac. The fact that the endolymphatic sac plays an immunologic role
      in the inner ear suggests that the infiltration of the Langerhans' cell may
      derive from it.

PMID- 14724489
TI  - Round window application of D-methionine, sodium thiosulfate, brain-derived
      neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced
      ototoxicity.
AB  - HYPOTHESIS: In this study we tested the effect of local administration of D
      methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast
      growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window
      membrane. BACKGROUND: Cisplatin is an important antineoplastic agent in the
      therapy of many malignancies. Its clinical utility is limited by severe side
      effects, including ototoxicity. Recent studies have shown protection against
      cisplatin ototoxicity in animal experiments by the systemic administration of D
      methionine and sodium thiosulfate. Growth factors such as brain-derived
      neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective
      effects in in vitro studies. METHODS: Osmotic pumps (Alzet) were implanted
      unilaterally in 30 guinea pigs. Five groups of six animals received either D
      methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived
      neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally
      for 5 consecutive days. Distortion product otoacoustic emissions were recorded
      every day. The animals were killed on day 6, and their cochleae were removed and
      analyzed by transmission electron microscopy. RESULTS: Compared with control
      animals, guinea pigs treated with D-methionine showed better otoacoustic
      emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not
      evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor,
      and fibroblast growth factor-2 showed no significant protective effect.
      CONCLUSION: Local application to the round window membrane can be used as an
      effective treatment in the prevention of cisplatin toxicity. Local application
      may avoid systemic side effects and reduce the antineoplastic effects of
      cisplatin.

PMID- 14724490
TI  - The suprameatal approach: an alternative surgical approach to cochlear
      implantation.
AB  - The suprameatal approach is an alternative method for performing cochlear
      implantation developed in the Sheba Medical Center in 1999. This technique
      eliminates the need for mastoidectomy and posterior tympanotomy. The middle ear
      is entered through a retroauricular tympanotomy flap, and the electrode is
      introduced into the cochlea via a tunnel drilled in the suprameatal region
      superior to Henle's spine. The suprameatal approach is a simple and safe
      technique that does not endanger the facial nerve nor the chorda tympani. A wide
      exposure of the promontory enables exact determination of scala tympani and
      smooth introduction of the electrodes into the cochlea. This technique may also
      be used in malformed or ossified cochlea. Until now 140 patients were operated in
      our department and an additional 48 patients were operated on in the department
      of Otorhinolaryngology at the University of Vienna employing the suprameatal
      approach technique.

PMID- 14724491
TI  - Malformation of stapes in VACTERLS association: a histopathologic study and three
      dimensional reconstruction.
AB  - OBJECTIVE: To investigate the temporal bone with a malformed stapes in VACTERLS
      association. STUDY DESIGN: The study design was a case report, histopathology of
      the temporal bone, and three-dimensional reconstruction of the ossicles and
      cochlea. SETTING: The study was carried out in the Temporal Bone Bank at Charles
      University, Hradec Kralove, on a case from Temporal Bone Foundation, Boston.
      PATIENT: A 1540-g, 41-cm female neonate with VACTERLS association, histopathology
      of the temporal bone, and three-dimensional reconstruction of the middle ear
      ossicles and cochlea. RESULTS: The posterior part of the footplate was missing,
      and the posterior crura of the stapes was not connected to the footplate but
      found freely suspended in the sinus tympani. CONCLUSION: Computer-assisted three
      dimensional reconstruction was performed from histologic sections of the temporal
      bone removed from a case of VACTERLS association. The reconstruction included
      structures such as the bony labyrinth and the middle ear ossicles. The
      abnormality observed in the reconstruction included the mislocation of the stapes
      and a shortened footplate.

PMID- 14724492
TI  - Intrathecal fluorescein to localize cerebrospinal fluid leakage in bilateral
      mondini dysplasia.
AB  - Recurrent meningitis caused by bilateral Mondini dysplasia presents a difficult
      diagnostic and therapeutic dilemma. A high-resolution computed tomographic scan
      with intrathecal contrast provided a false-positive identification for the side
      of cerebrospinal fluid leak in this patient. We report the intraoperative use of
      intrathecal fluorescein with mastoid tap to identify the side of cerebrospinal
      fluid leak in a 16-month-old boy with bilateral Mondini malformations. Both ears
      had been obliterated for recurrent cerebrospinal fluid leaks, while meningitis
      occurred after unilateral cochlear implantation.

PMID- 14724493
TI  - Postflight balance control recovery in an elderly astronaut: a case report.
AB  - OBJECTIVE: To examine the sensorimotor adaptive response of a 77-year-old man
      exposed to the gravito-inertial challenges of orbital space flight. STUDY DESIGN:
      Prospective case study with retrospective comparisons. SETTING: NASA
      Neurosciences Laboratory (Johnson Space Center) and Baseline Data Collection
      Facility (Kennedy Space Center). PRIMARY PARTICIPANT: One 77-year-old male
      shuttle astronaut. INTERVENTION: Insertion into low Earth orbit was used to
      remove gravitational stimuli and thereby trigger sensorimotor adaptation to the
      microgravity environment. Graviceptor stimulation was reintroduced at landing,
      and sensorimotor readaptation to the terrestrial environment was tracked to
      completion. MAIN OUTCOME MEASURES: Computerized dynamic posturography tests were
      administered before and after orbital flight to determine the magnitude and time
      course of recovery. RESULTS: The elderly astronaut exhibited balance control
      performance decrements on landing day; however, there were no significant
      differences between his performance and that of younger astronauts tested on the
      same shuttle mission or on previous shuttle missions of similar duration.
      CONCLUSIONS: These results demonstrate that the physiological changes attributed
      to aging do not necessarily impair adaptive sensorimotor control processes.

PMID- 14724494
TI  - Functional and anatomic alterations in the gentamicin-damaged vestibular system
      in the guinea pig.
AB  - HYPOTHESIS: The purpose of this study was to investigate the expected functional
      and morphologic effect of gentamicin on the vestibular system simultaneously by
      measurement of vestibular evoked potentials and electron microscopic evaluation.
      BACKGROUND: Vestibular short-latency evoked potentials to linear acceleration
      have been shown to be a useful parameter of vestibular function. In gentamicin
      treated animals, the morphologic damage has been well documented, although this
      has seldom been quantified. METHODS: Fifteen guinea pigs were divided into three
      equal groups. Two groups received different dosages of intramuscular gentamicin
      for 3 weeks; the third group was the control group. Vestibular short-latency
      evoked potentials to linear acceleration pulses were measured. After the last
      gentamicin dose, the utricles were prepared for scanning and transmission
      electron microscopy. On scanning electron microscopy photographs, the surface
      area damage ratio of the utricles, a simple method of quantifying gross
      morphologic damage, was calculated. RESULTS: The vestibular short-latency evoked
      potential of gentamicin-treated guinea pigs showed a slow-developing, damaging,
      dose-response effect on the function of the vestibular system (p = 0.01).
      Scanning electron microscopy and transmission electron microscopy showed severe
      morphologic damage in the sensory hair cells of the utricle. The surface area
      damage ratio showed a dose-response relationship (p = 0.01). CONCLUSION:
      Functional and anatomic alterations in the gentamicin-damaged vestibular system
      in the guinea pig are related.

PMID- 14724495
TI  - Cervico-ocular reflex in normal subjects and patients with unilateral vestibular
      hypofunction.
AB  - OBJECTIVE: To determine whether the cervico-ocular reflex contributes to gaze
      stability in patients with unilateral vestibular hypofunction. STUDY DESIGN:
      Prospective study. SETTING: Tertiary referral center. PATIENTS: Patients with
      unilateral vestibular hypofunction (n = 3) before and after vestibular
      rehabilitation and healthy subjects (n = 7). INTERVENTIONS: Vestibular
      rehabilitation. MAIN OUTCOME MEASURES: We measured the cervico-ocular reflex in
      patients with unilateral vestibular hypofunction before and after vestibular
      rehabilitation and in healthy subjects. To measure the cervico-ocular reflex, we
      recorded eye movements with a scleral search coil while the trunk moved at 0.3,
      1.0, and 1.5 Hz beneath a stabilized head. To determine whether the head was
      truly stabilized, we measured head movement using a search coil. RESULTS: We
      found no evidence of cervico-ocular reflex in any of the seven healthy subjects
      or in two of the patients with unilateral vestibular hypofunction. In one patient
      with chronic unilateral vestibular hypofunction, the cervico-ocular reflex was
      present before vestibular rehabilitation only for leftward trunk rotation
      (relative head rotation toward the intact side). After 5 weeks of placebo
      exercises, there was no change in the cervico-ocular reflex. After an additional
      5 weeks that included vestibular exercises, cervico-ocular reflex gain for
      leftward trunk rotation had increased threefold. In addition, there was now
      evidence of a cervico-ocular reflex for rightward trunk rotation, potentially
      compensating for the vestibular deficit. CONCLUSION: The cervico-ocular reflex
      appears to be a highly inconsistent mechanism. The change of the cervico-ocular
      reflex in one patient after vestibular exercises suggests that the cervico-ocular
      reflex may be adaptable in some patients.

PMID- 14724496
TI  - Adam Politzer (1835-1920): his medical studies and publications in Hungarian.
AB  - OBJECTIVE: Adam Politzer was one of the most well-known otologists of the 19th
      century. Unfortunately, very little is known about his life during his years as a
      medical student and about his publications in Hungarian. The aim of this study is
      to summarize Politzer's student years between 1854 and 1859 and his 13
      publications in Hungarian. DATA SOURCES: Eleven of Politzer's 13 Hungarian
      publications were published while he was a student, and the remaining two were
      published in 1862 and 1908. These are rarely mentioned in Politzer's curriculum
      vitae. CONCLUSION: The student publications concern only general medicine and
      deal with pleural effusion, pernicious anemia and iron deficiency, lung
      emphysema, bronchitis, ischialgia, Bright disease of the kidney, hepatic cancer,
      acute yellow atrophy of the liver, cystovarium, ectopic kidney, and ejaculatio
      praecox. This broad array of diseases demonstrates once again that to be a good
      otologist, it is necessary to have an open mind concerning others parts of the
      body. Along with the different influences of his teachers, this certainly
      explains why Politzer reached such a high a level in otology. The last two
      publications in Hungarian concern otology and deal with the effect of mud ear on
      parts of hearing (1862) and acute suppurative otitis media (1908).

PMID- 14724497
TI  - Primary paraganglioma of the facial nerve canal.

PMID- 14724498
TI  - Hurler disease.

PMID- 14724499
TI  - The meaning of health for women with physical disabilities: a qualitative
      analysis.
AB  - Researchers used qualitative research methods to explore determinants of and
      barriers to the health of women with physical disabilities. Semistructured, open
      ended interviews were conducted with one focus group (n=9) and 9 individual women
      with various physical disabilities. PARTICIPANTS: (1) defined physical health as
      a correlate of functional capacity; (2) noted the importance of a positive mental
      state; (3) recognized the effect of having or lacking social support; (4)
      described the role of health behaviors in health promotion, as adapted to their
      functional limitations; and (5) described problems with their medical
      practitioners' lack of knowledge. Barriers included certain disability
      characteristics, stress, inadequate social support, societal attitudes, and lack
      of resources.

PMID- 14724500
TI  - Adverse health behaviors and chronic conditions in working-age women with
      disabilities.
AB  - This retrospective, cross-sectional, multiple cohort study of women with
      disabilities addresses two health-related areas in a nationally representative
      sample of women living in the community. Using data from the 1997-1998 National
      Health Interview Survey (NHIS), health risk behaviors and chronic conditions were
      examined for women with mild, moderate, and severe functional limitations, and
      their responses were compared to those of women who reported no limitations.
      Women with severe limitations evidenced the highest risk for heavy cigarette
      smoking. They were also more likely to meet the Body Mass Index criterion for
      obesity. Adverse health behaviors were strongly associated with the five
      potentially disabling chronic conditions that were studied.

PMID- 14724501
TI  - Evaluating a Medicaid home and community-based physical disability waiver.
AB  - State Medicaid waivers have fostered innovative health delivery systems for
      persons with special needs. Yet their overall cost effectiveness remains poorly
      understood. Changes were recently analyzed in Medicaid health services and costs
      for persons newly enrolled in the Kansas Physical Disability (PD) Waiver and
      found that ambulatory services increased, consistent with meeting enrollees'
      unmet medical needs and their access to enriched services. Home health,
      transportation, and personal care services also rose. Though not significant,
      hospital inpatient, outpatient, and long-term care services declined. This
      movement towards community-based service use in the short term reflects improved
      self-directed care and possible long-term cost savings.

PMID- 14724502
TI  - Best practices for inclusive child and adolescent out-of-school care: a review of
      the literature.
AB  - Inclusion or full participation by children with disabilities in programs and
      activities designed for typically developing children benefits children with and
      without disabilities and their families. Inclusive care programs are least
      available for school-age children and adolescents. A review of the literature
      identified best practices for effective inclusive out-of-school care, including:
      a written program philosophy; a written plan for inclusive programs; strong
      leadership; a disability awareness program for staff and children; training and
      support for staff; sufficient staff to meet program needs; a working
      communication and collaboration; an adapted setting, activities, and time
      parameters; proficient collaboration with families; and an evaluation plan.

PMID- 14724503
TI  - Perception of health status by homeless US veterans.
AB  - Perceptions of health status among 331 homeless veterans and homeless nonveterans
      were examined. Homeless veterans were significantly less apt to perceive their
      health as fair/poor (8%) compared to non-veteran homeless men (19%). Homeless
      veterans were also more likely to report having a regular source of care (57%
      versus 36%). Logistic regression analysis indicated the adjusted odds of
      fair/poor health were more than two times greater for persons reporting
      depressive symptomatology than for those without this history; veterans continue
      to remain less likely to report fair/poor health than nonveterans. High rates of
      substance abuse were observed for the entire sample. Such differences in
      perceived health result in important health access issues.

PMID- 14724504
TI  - What makes it so hard? Barriers to health promotion experienced by people with
      multiple sclerosis and polio.
AB  - Perceptions of barriers to health promotion were examined in three groups of
      individuals with disabilities: (1) those with multiple sclerosis, (2) those with
      postpolio syndrome, and (3) polio survivors without postpolio syndrome. While
      there were small statistically significant differences among the three groups,
      all rated fatigue and impairment as their most frequent problems. For all groups,
      financial and interpersonal resources contributed significantly to the prediction
      of barriers, after accounting for perceived impairment. The findings suggest that
      health professionals should explore thoroughly the nature of individuals'
      perceived barriers to staying healthy, so that they can target their health
      promoting interventions most effectively.

PMID- 14724505
TI  - Disability rites: the cultural shift following impairment.
AB  - Persons with disabilities experience barriers to health within a culture. The
      local culture assigns meanings to those with impairments and their activities. In
      order to understand the experience of disability as influenced by culture,
      anthropological models of rites of passage and liminality have been used, but
      these can be extended further. The authors posit that local cultures should be
      the context for studying disability, and thus extend on previous work by Murphy
      on the rites of passage for persons with disabilities. This article will: (1)
      review how disability has been culturally created and defined, (2) provide
      additional evidence for the argument regarding the existence of disability
      culture, and (3) extend the work on rites of passage for persons with
      disabilities. A brief discussion of how this expanded model might guide the
      understanding of disability and the understanding of barriers to health follows.

PMID- 14724511
TI  - [Contention during venous leg ulcers in the era of "evidence-based medicine"].

PMID- 14724512
TI  - [Treatment of erosive oral lichen planus with thalidomide].
AB  - INTRODUCTION: Treatment of erosive oral lichen planus is difficult and often
      requires the use of systemic corticosteroids. This severe condition may lead to
      weight loss and impairment of patients' general condition due to painful oral
      erosions. The aim of this study was to evaluate the usefulness of thalidomide in
      the treatment of severe erosive oral lichen planus. PATIENTS AND METHODS: The
      efficacy and safety of thalidomide were retrospectively evaluated in 6 patients
      with severe erosive lichen planus resistant or relapsing despite high doses of
      oral corticosteroids. Thalidomide was started at an initial dose of 50 to 100
      mg/day and was then progressively decreased to the minimal effective dose. Follow
      up evaluations were performed every two months by the same dermatologist.
      RESULTS: Complete healing of erosive lesions was observed in 4 of 6 patients
      after a mean duration of 4 months. Partial epithelialization of erosive lesions,
      disappearance of dysphagia and weight gain were observed in one patient.
      Treatment failed in the last patient. The mean dose of prednisone of the 3
      patients receiving both thalidomide and oral corticosteroids decreased from 37
      mg/day at the beginning of the study to 7 mg/day at the end of the study. Two
      patients experienced severe side effects: phlebitis and neuropathy, leading to
      thalidomide discontinuation. Oral erosions rapidly relapsed after withdrawal of
      thalidomide. DISCUSSION: Thalidomide seems to be an effective treatment of severe
      corticosteroid resistant and dependent or when systemic corticosteroids are
      contraindicated erosive oral lichen planus. Potentially serious side effects
      should restrict its use to the most severe forms of the disease.

PMID- 14724513
TI  - [Chronic urticaria, thyroiditis and autologous serum test].
AB  - INTRODUCTION: The autoimmune nature of certain forms of chronic urticaria remains
      debatable. Aim of the study. To find a correlation in terms of autoimmune pattern
      between chronic urticaria and thyroiditis using the autologous serum test and the
      search for anti-thyroid antibodies. PATIENTS AND METHODS: Study in a single
      center of 59 patients having consulted for urticaria that had progressed for more
      than six weeks and without precise etiology. An autologous serum test was
      conducted and anti-thyroid autoantibodies were searched for in the serum stored
      after the test. RESULTS: Out of 59 patients, 51 had an interpretable autologous
      serum test and 57 underwent research for anti-thyroid antibodies. Twelve patients
      out 57 (21 p.cent) exhibited one or more types of positive (n=10) or borderline
      (n=2) anti-thyroid antibodies, and eight out of 12 (66.6 p.cent) had a known
      thyroid disease before the onset of urticaria. The systematic blood test
      permitted the discovery of 4 cases of unknown anti-thyroid antibodies. The
      symptoms regressed in two of these patients without any specific treatment, one
      patient was treated with L thyroxin for hyperthyroidism without any improvement
      in the symptoms and one other patient had normal thyroid function. Among these 12
      patients, 11 underwent autologous serum tests, but only 3 of them exhibited
      clearly positive results and one was doubtful. CONCLUSIONS: Within the limits of
      this study, we found a 21 p.cent rate of patients with chronic urticaria
      exhibiting one or more anti-thyroid antibodies. The positivity of the autologous
      serum test does not appear to be related with autoimmune thyroid disorders.

PMID- 14724514
TI  - [Prospective epidemiological study on cutaneous melanomas in the Vendee area].
AB  - INTRODUCTION: The aim of this prospective study was to evaluate the incidence of
      melanoma in the Vendee area, coastal region of Eastern France, in 1997. PATIENTS
      AND METHODS: The 16 dermatologists in the Vendee area in 1997, grouped together
      in a local association, completed a sheet for each patient in whom a new melanoma
      had been diagnosed. During the same period, the hospital and private pathologists
      of the Vendee and surrounding areas reported their new cases of melanoma in
      patients residing at least six months of the year in the area. The data
      concerning the local population was supplied by the INSEE (French national
      institute of economic and statistical information) and the CPAM (French health
      authority) supplied data on the practitioners' activity. The raw and standardized
      incidence was calculated by the epidemiologist and the statistician of the local
      Vendee Cancer registry. RESULTS: One hundred fifteen new melanomas were diagnosed
      in Vendee in 1997, 97 by a dermatologist and 18 declared by a pathologist. There
      were 36 in situ and 79 invasive melanomas discovered in 68 women and 47 men (sex
      ratio: 1.46). The standardized rate of incidence according to the world model was
      of 98/100,000 for women and 7.8/100,000 for men. The frequency curve revealed two
      peaks: the first at 40-50 years of age and the second at 70-75. The mean Breslow
      index of the 79 invasive cancers was of 1.62 mm (range: 0.10-12.5 mm). The only
      statistically significant difference between the melanomas of the men and the
      women concerned the topography; there were more melanomas on the trunk in men and
      more melanomas on the lower limbs in the women. Forty-seven Dubreuilh melanomas
      were reported: 28 in situ and 19 invasive. DISCUSSION: This prospective study
      determined the incidence of melanoma in Vendee in 1997. The figures have been
      compared with those of the Vendee cancer registry, founded in April 1997, and
      with those of various published studies. The comparison was difficult because of
      the difference in study methodology. The only figures obtained in the same
      conditions are those of the cancer registry and we compared them with those of
      the Haut-Rhin, area of Eastern France: the incidence was similar for the women in
      the two areas and greater for the men in the Haut-Rhin with regard to the
      invasive melanomas. Conversely, 44 in situ melanomas were declared in the Haut
      Rhin over a 3 year period versus 37 in Vendee over a period of 1 year. The
      increase in the incidence of melanoma in Vendee in the years to come should
      permit the evaluation of the impact of the various preventive campaigns.

PMID- 14724515
TI  - [Prospective clinical study on new cutaneous melanomas in the Vendee area].
AB  - INTRODUCTION: In parallel to an epidemiological study on the new cases of
      melanoma reported in the Vendee area in 1997, private dermatologists conducted a
      clinical analysis of the characteristics of melanomas (including Dubreuilh's
      melanoma) and of the population concerned. PATIENTS AND METHODS: For each patient
      in whom a melanoma had been diagnosed, the dermatologists completed a
      standardized sheet that included the identification, phototype (comparing the
      distribution with that of the local population, studied in all the consultants
      during a randomly selected week), the personal and family history of melanoma,
      the existence of severe sunburn and exposure to artificial ultra-violet rays, the
      screening method, the time lapse before treatment, the impact of information
      campaigns, the number of nevi, atypical or not, and the characteristics of the
      tumor. The exeresis method and the histological characteristics (type, Clark's
      score and Breslow's index) were also noted. RESULTS: In 1997, the 16 local
      dermatologists diagnosed 97 melanomas in 55 women and 42 men with a mean age of
      64 years. There was no statistically significant difference between the melanomas
      of the men and those of the women, other than their localization. Photoype II was
      significantly more frequent in the population exhibiting a melanoma. Sun exposure
      was moderate or intensive for three thirds of the patients. Past history of
      severe sunburn was twofold more frequent in the patients exhibiting a melanoma on
      the trunk. The association of many nevi was noted in a little more than half of
      the patients, and with atypical nevi in 5.2 p.cent. The elements that alerted the
      patients were recorded. The time lapse before diagnosis was calculated in months
      for nodular and in years for superficial melanomas. Clark's score and Breslow's
      index are presented in a table. DISCUSSION: Our study underlines several
      interesting features: the fairly high mean age on discovery, a high rate of
      invasive melanomas, and patients less well informed than in the Ile de France
      area. These results should open the debate on the best way to educate the
      population concerned so as to reduce the incidence of this malignant tumor.

PMID- 14724516
TI  - [Non-melanoma skin cancers and human papillomavirus].
AB  - Ultraviolet radiation (UV) is considered as a key environmental risk factor of
      non-melanoma skin cancer (NMSC), but other factors such as immunological status,
      genetic predisposition and infection by human papillomavirus (HPV) may also be
      involved. Although there is overwhelming epidemiological and molecular evidence
      that indicates a direct role for specific mucosal HPV-types in anogenital
      cancers, in particular cervical cancer, the pathogenic role of HPV in the
      development of NMSC remains speculative. The association between HPV and NMSC was
      first identified in patients with epidermodysplasia verruciformis (EV) and later
      in recipients of organ transplants. All these patients develop NMSC at sun
      exposed sites. Cutaneous and mucosal HPV-DNA have been detected in about 60 to 90
      p. 100 of NMSC, but also in benign epithelial lesions, and even in normal skin.
      However and although at a lower rate (about 40 p. 100), HPV-DNA have also been
      detected in normal skin, in particular in hair follicles, and in premalignant
      lesions and in NMSC from non-EV and immunocompetent subjects. Furthermore, no
      particular HPV type predominates and the viral load in NMSC seems lower than in
      benign epithelial lesions. Although all these findings argue against a direct
      involvement of HPV in NMSC, they may suggest a "hit and run" mechanism which no
      longer requires the viral agent but the activity of HPV oncoproteins. High risk
      mucosal HPV-types encode two major oncoproteins, E6 and E7, which inactivate two
      suppressor proteins, p53 and pRb respectively, and are sufficient for host-cell
      immortalization. A polymorphism resulting in either a proline or an arginine at
      codon 72 may also be a relevant risk factor for mucosal HPV-types-associated
      NMSC. By contrast, E6 of skin HPV-types fails to interact with p53, but prevents
      infected cells from UV-induced apoptosis leading thus to the propagation of
      deleterious UV-induced mutations. Immunosuppressive activities of HPV E6 and E7
      proteins permit persistent HPV infection and the impairment of immunologic
      removal of UV-damaged cells. These results support a role for HPV infection in
      skin carcinogenesis as a co-factor in association with UV and immunosuppression.

PMID- 14724517
TI  - [Lethal neurological involvement during incontinentia pigmenti].
AB  - INTRODUCTION: We present a case of incontinentia pigmenti associated with lethal
      neurological involvement. CASE REPORT: A newborn, three day-old female child
      presented with an erythromatous vesicular eruption and epileptic seizures
      secondary to extensive necrosis of the brain tissue. She died at 13 days of age
      following a seizure. The genetic analysis concluded in a sporadic case of
      incontinentia pigmenti. DISCUSSION: Thirty-eight cases of incontinentia pigmenti,
      associated with severe brain damage have been reported in the literature. The
      neurological manifestations appear rapidly after birth in the form of epilepsy.
      The seizures can lead to severe psychomotor retardation and, in most cases,
      precede the installation of motor deficiency. The lesions observed on imaging are
      hypodensity of varying localization and which do not correspond to any
      vascularization pattern. Autopsy reveals areas of brain tissue destruction.
      Recent genetic data suggest two physiopathological hypotheses, which both rely on
      NF-Kb dysfunction. The cutaneous cells expressing muted chromosome x exhibit a
      reduced rate of free NF-kB and are more sensitive to the apoptotic signals. Like
      the cutaneous cells, the brain tissue cells expressing muted chromosome x may be
      eliminated when becoming apoptotic. Furthermore, NF-kB is one of the links of the
      transduction system of the messages received by the VEGF receptor, the
      endothelial growth factor. A perturbation of the transmission of this message
      might alter cerebral microvascularization.

PMID- 14724518
TI  - [KID syndrome: a cause of pachydermatoglyphia].
AB  - INTRODUCTION: The KID syndrome is a rare ectodermal dysplasia associating
      erythrokeratodermia, deafness and keratitis. Other disorders such as sensitivity
      to infections or hypohidrosis may be associated. Pachydermatoglyphia is
      characterized by diffuse hyperkeratosis in which the dermatoglyphe crests are
      accentuated in thickness and height. CASE REPORT: We report the case of a KID
      syndrome in a young girl, born of non-consanguine parents and without any
      familial context. The classical elements of this dysplasia were present:
      erythrokeratoderma with dryness and roughness of the whole tegument, plicatured
      pachydermia of the knees, facial erythema, grooves around the mouth,
      hypotrichosis of the lashes and eyebrows, deafness, and ophthalmologic
      involvement. Involvement of the palms was characterized by the
      pachydermatoglyphic aspect. DISCUSSION: In this case report, the palmar
      keratoderma corresponded to the original description of pachydermatoglyphia and
      we consider that the KID syndrome should be integrated as a possible etiology of
      pachydermatoglyphia.

PMID- 14724519
TI  - [Fluindione-induced acute exanthematous pustulosis with renal involvement].
AB  - INTRODUCTION: Fluindione (Previscan) is an oral anti-vitamin K anticoagulant,
      widely prescribed in France. Contrary to phenindione, which is also an
      indanedione derivative, very few cases of immunoallergic reactions have been
      described. CASE REPORT: A 68 year-old man, treated with fluindione for cardiac
      arrhythmia, presented with a pustular eruption and erythema twenty days after
      initiation of treatment. The eruption was associated with hyperthermia,
      arthralgia, neutrophilia (11,000/mm2), hepatic cytolysis and renal involvement
      including acute renal failure, hematuria and proteinuria. In view of the absence
      of any earlier case in the literature, we did not impute fluindione and the drug
      was reintroduced and led to the rapid recurrence of all the same manifestations.
      DISCUSSION: These manifestations were consistent with an immunoallergic reaction
      to fluindione (probable intrinsic imputability I3) and acute interstitial
      nephritis (probable intrinsic imputability I3). We believe this is the first case
      of acute generalized exanthematous pustulosis induced by fluindione (intrinsic
      imputability Bo). A few rare cases of fluindione-induced hypersensitivity
      reactions and acute interstitial nephritis, however, have been described.

PMID- 14724520
TI  - [Kikuchi's disease associated with cutaneous manifestations evoking Well's
      syndrome].
AB  - BACKGROUND: Wells' syndrome is a dermatological disease with polymorphous lesions
      characterized histologically by an eosinophilic infiltrate of the dermis with
      edema and flame figures. Kikuchi's disease is a benign cause of lymphadenitis
      corresponding histologically to a necrotizing histiocyting adenitis without
      neutrophils. We describe the association of a Kikuchi's disease and cutaneous
      lesions similar to Wells'syndrome. OBSERVATION: A 62-year-old man presented over
      3 years several simultaneous episodes of left axillary lymphadenitis and of
      cutaneous lesions compatible with a diagnosis of Wells'syndrome. No precipitating
      event or disease described with the Wells'syndrome was established. Concerning
      the axillary nodes, a cancer, a lymphoproliferative syndrome, a systemic lupus
      and several infectious diseases were excluded. Standard histology and
      immunochemistry of a lymph node showed signs of Kikuchi's disease. Bilateral
      anterior uveitis was incidentally detected. The three conditions improved with
      oral corticosteroids (1 mg/kg/d). DISCUSSION: The patient had Kikuchi's disease
      and a recurrent dermatosis for which the clinical and histological aspects, the
      evolution and the absence of arguments for another cause, suggest a
      Wells'syndrome. Cutaneous manifestations occur in 16 to 40 p. 100 of cases of
      Kikuchi's disease and often have characteristic histologic features not
      corresponding to Wells'syndrome. The association of the 2 diseases may be then
      incidental, despite 4 simultaneous episodes. Two viral agents, VIH and VZV have
      been associated with the two diseases but do not seem to be the cause in our
      patient. Concerning the anterior uveitis, a single case of uveitis has been
      described for each condition.

PMID- 14724521
TI  - [Perifolliculitis capitis abscedens and suffodiens].

PMID- 14724522
TI  - [Infiltrated inguinal lesion].

PMID- 14724523
TI  - [Multiple cephalic tumors].

PMID- 14724524
TI  - [Tatoo removal techniques].

PMID- 14724525
TI  - [Nodular basal cell carcinoma].

PMID- 14724526
TI  - [Keratoacanthoma].

PMID- 14724527
TI  - [A mouse with an active disease as a model for pemphigus].

PMID- 14724528
TI  - [Lichen sclerous and atrophicus of palms and wrists].

PMID- 14724529
TI  - [Ergotism, smallpox and halo-nevus at the onset of the sixteenth century].

PMID- 14724531
TI  - [L.-M. Pautrier, "Doctor Honoris causa" distinction of the Coimbra University].

PMID- 14724532
TI  - [Is microchimerism a reality in dermatology?].

PMID- 14724533
TI  - [The follow-up of anogenital warts in a specialized consultation: study of
      patients lost to follow-up].
AB  - INTRODUCTION: The treatment of condylomata acuminata relies on prolonged
      management, partly related to the need for repeated applications with regard to
      destructive therapeutic measures and the clinical supervision because of the high
      prevalence of relapses. This implies that patients are ready to consult their
      doctor at regular intervals during a relatively prolonged period of time. We
      wanted to assess the patients lost to follow-up in a population of patients
      exhibiting anogenital warts together with the factors associated with the loss to
      follow-up. PATIENTS AND METHODS: This was a prospective observational study
      conducted in France among dermatologists and gynecologists between May and
      December 2000. The physicians were free to prescribe the treatment of their
      choice. The social data of the patients and the classical characteristics of the
      condylomata acuminata were assessed. A patient was considered as lost to follow
      up when he/she no longer came in for the consultation assessing the treatment.
      The data of the patients lost to follow-up were compared to those of the other
      patients. RESULTS: Two hundred ninety-seven cases, with 57 p. 100 men, were
      included during the study period. The mean age of the patients was of 33.8 +/-
      11.4 years, with 43 p. 100 of patients aged under 30. In 40 p. 100 of cases, the
      lesions had existed for more than 3 months and were symptomatic in 30 p. 100 of
      cases. At the end of the study, 28.3 p. 100 of patients were considered as lost
      to follow-up. With multivariate analysis, the loss to follow-up appeared related
      to the patients' age (more frequent, the younger the patient; p<0.04) and not to
      the fixing of a precise appointment at the end of treatment (p<0.001). The
      asymptomatic nature of the lesions, recognized as a loss to follow-up risk factor
      in univariate analysis, was at the limit of significance in multivariate analysis
      (p=0.06). DISCUSSION: Clinicians should be particularly attentive with young and
      asymptomatic patients that they treat for condylomata acuminata, and attempt to
      reduce the rate of lost to follow-up and improve the quality of their management.

PMID- 14724534
TI  - [Non infectious skin conditions associated with diabetes mellitus: a prospective
      study of 308 cases].
AB  - INTRODUCTION: Non-infectious dermatoses during diabetes appear frequent if one
      refers to some of the studies in the literature that have attempted to assess its
      prevalence. PATIENTS AND METHODS: From November 2000 to November 2001, 308
      randomly selected, hospitalized, diabetic patients were examined. The data were
      collected prospectively and systematically in a pre-established questionnaire.
      Statistical analysis included a descriptive and univariate analysis. RESULTS:
      206/308 diabetics (67 p. 100) exhibited at least one non-infectious dermatitis,
      the most frequent of which was cutaneous xerosis (39 p. 100), diabetic dermopathy
      (24 p. 100), facial erythrosis (24 p. 100), purpural and pigmented capillaritis
      of the legs (20 p. 100), xanthochromia (12 p. 100) pseudo-scleroderma (8 p. 100)
      and acanthosis nigricans (7 p. 100). The non-infectious dermatoses were globally
      more frequent in type II diabetic patients exhibiting at least one microvascular
      complication. DISCUSSION: This study is the first French prospective work on the
      subject. We found a prevalence of non-infectious dermatoses during diabetes close
      to that of the major studies in the literature. Some of these dermatoses are
      markers of macrovascular (acanthosis nigricans, purpural and pigmented
      capillarity) or microvascular (xerosis, acanthosis nigricans, purpural and
      pigmented capillarity, Dupuytren's disease) complications for type II diabetes or
      are markers of auto-immunity (alopecia areata, vitiligo) for type I.

PMID- 14724535
TI  - [Multiple familial cutaneous leiomyoma].
AB  - INTRODUCTION: Cutaneous leiomyoma is a benign tumor, the discovery of which may
      suggest a hereditary form. We report a family in which 5 generations developed
      cutaneous and uterine leiomyomas. The originality of this report lies in the
      large number of generations developing the disease and the association with
      chronic myeloid leukemia. OBSERVATIONS: We have studied 16 members of a family
      with cutaneous and uterine leiomyomas spanning five generations. Eight members of
      the family (6 women and 2 men) presented with cutaneous leiomyomas. All 6 women
      also had uterine myomas with complications (menometrorrhagia, miscarriage,
      premature delivery and hysterectomy). Pathological association was also
      confirmed: polycythemia (1 case), papillary renal carcinoma (1 case) and chronic
      myeloid leukemia (1 case). DISCUSSION: Piloleiomyoma can develop sporadically or
      can be transmitted genetically. To our knowledge, we report the fifth case of a
      family of more than 2 generations presenting with piloleiomyoma. By studying the
      family tree, we were able to confirm the dominant autosomal nature of the mode of
      transmission found by other authors. The association of piloleiomyoma and uterine
      myoma is classified as Reed's syndrome. In such cases, the uterine myoma requires
      particularly careful monitoring since it is associated with significant risk of
      gynecological complications (menometrorrhagia, miscarriage, premature delivery
      and postpartum hemorrhage). Moreover, in our observations we describe diseases
      associated with piloleiomyoma: polycythemia (1 case), papillary renal carcinoma
      (1 case), but also the association of piloleiomyoma with chronic myeloid leukemia
      (1 case). A previous report described the same genetic deletion in uterine myoma
      as in chronic myeloid leukemia, which gives further weight to this association.

PMID- 14724536
TI  - [Cutaneous tuberculosis: anatomoclinical features and clinical course (26
      cases)].
AB  - INTRODUCTION: Despite prevention programs, tuberculosis is still progressing
      endemically in developing countries. The prevalence of cutaneous tuberculosis is
      estimated as 2.1 p. 100 and represents a rare localization among the extra
      pulmonary forms. In order to study the epidemiology, the most frequent
      anatomoclinical forms and the progressive features of cutaneous tuberculosis, we
      conducted a study in the area of Tunis over a 20-year period. PATIENTS AND
      METHODS: All cases of cutaneous tuberculosis observed between 1981 and 2000 in
      the dermatology department of the Habib Thameur hospital were included in a
      retrospective study. Diagnosis of cutaneous tuberculosis was challenging and
      required the correlation of clinical, biological and progressive features.
      RESULTS: Twenty-six patients were observed in the study. There were 12 men and 14
      women with a mean age of 30.4 years (range: 6-74) and 20 p. 100 of infantile
      cases. Of the various patterns of cutaneous tuberculosis seen, 11 (42 p. 100) had
      lupus tuberculosis, 10 (38 p. 100) had scrofuloderma, 4 (15 p. 100) had
      tuberculosis verrucosa cutis and 1 child had a perianal tubercular ulcer. The
      Mantoux test was positive in 20/24 patients. Histological tuberculoid granuloma
      was seen in 25 cases (96 p. 100) associated with caseating necrosis in 10 cases
      (38 p. 100). All patients were treated successfully with triple or quadruple anti
      tubercular drugs for 6 to 10 months. One patient exhibited a squamous cell
      carcinoma on a lupus tuberculosis scar four years later. DISCUSSION: The
      progression of cutaneous tuberculosis remains stable, ranging from 1.4 cases/year
      between 1981 and 1990 to 1.2 cases/year between 1991 and 2000. In our study,
      females were slightly more affected than men with a M/F sex ration of 0.86.
      Before 1984, scrofuloderma was the most frequent form among the cutaneous
      tuberculoses. Now the frequency of lupus tuberculosis has reached that of
      scrofuloderma, demonstrating the increase in the incidence of clinical pattern of
      cutaneous tuberculosis with strong immunity probably related to the improvement
      in health conditions and generalization of vaccination programs.

PMID- 14724537
TI  - [Molecular markers associated to prognosis of melanoma].
AB  - Melanoma prognosis is based on histological criteria such as tumor thickness
      (measured by Breslow index), level of invasion (Clarck's level), presence of
      ulceration and number of mitoses per mm2. However, these parameters do not
      provide a precise prognosis in all cases: thin melanomas may develop metastases
      and thick melanomas may remain focalized for many years. For these reasons, the
      search for other prognostic factors is still ongoing. Many molecules play a part
      in the invasiveness and metastatic dissemination of melanoma have now been
      identified. Expression of these molecules has been studied in primary melanoma
      and correlated with prognosis. An increase in the number of cells positive for
      Ki67 (detected by Mib1), cycline A, cycline D, p35, MMp-2, beta1 and beta3
      integrins, osteonectin, the presence of an intense inflammatory infiltrate and
      capillary invasion are considered as factors of poor prognosis as well as the
      decrease in p16, p27, Melan A and nm23. The significance of CD44 modifications is
      still controversial. Only a small number of these different proteins has a
      prognostic value independent of tumor thickness. These results need to be
      confirmed on larger series of patients. Additional hope is given to new
      techniques such as the analysis of the genes implied in tumor progression by
      microarray technique in such a way as to provide a molecular map of each tumor.

PMID- 14724538
TI  - [Hypomelanosis of Ito in a girl with Trisomy 13 mosaicism: a cytogenetic study].
AB  - BACKGROUND: Hypomelanosis of Ito was first described by Ito in 1952 as
      incontinentia pigmenti achromians. The consistent feature of the disease is a
      characteristic cutaneous hypopigmentation area following the lines of Blaschko,
      but the clinical manifestations are varied and hypomelanosis of Ito is regarded
      as a neurocutaneous syndrome. Hypomelanosis of Ito is sporadic but is probably a
      non-specific expression of chromosomal mosaicism; we report a case with four
      clones. CASE REPORT: We report the case of a 26 year-old woman with
      neurocutaneous hypomelanosis of Ito and Trisomy 13 mosaicism. She also exhibited
      skeletal and ophthalmologic disorders. Immunohistology revealed a PS100 and Melan
      A decrease in hypopigmented skin. Cytogenetic study of normal and hypopigmented
      skin fibroblasts showed mosaicism with four clones. DISCUSSION: This is the third
      case of Trisomy 13 mosaicism associated with hypomelanosis of Ito, although other
      anomalies on chromosome 13 have been described. Happle published "phylloid"
      pigmented cases, which are mainly associated with Trisomy 13. This is the first
      observation of four-clone mosaicism and can be explained by successive mutations
      during embryogenesis. Anomalies on chromosomes 5,6 and 21 have never been
      described. The definition of hypomelanosis of Ito is not well established and the
      disease is presently included in a group of "pigmentary dysplasia" with genetic
      mosaicism.

PMID- 14724539
TI  - [Amyloidosis complicating psoriatic arthritis].
AB  - BACKGROUND: Secondary AA amyloidosis is a classical complication of rheumatismal
      or chronic infectious diseases. Psoriasis is a rare cause of secondary
      amyloidosis with only around thirty cases reported in the literature. CASE
      REPORT: A 62 year-old man exhibited cutaneous lesions of psoriasis for six years
      complicated by articular involvement over the past year. The occurrence of an
      isolated proteinuria revealed renal and hepatic AA amyloidosis. Treatment with
      methotrexate (Methrotrexate), enalapril (Renitec) and colchicine (Colchicine) was
      initiated and led to a stabilization of the proteinuria for two years.
      DISCUSSION: In psoriatic patients, secondary amyloidosis mainly complicates the
      arthritic diseases of prolonged progression. Our case report is original in the
      rapid onset of amyloidosis after the first articular signs. The clinical
      manifestations of secondary amyloidosis are related to renal or gastrointestinal
      involvement. Prognosis is usually poor. Treatment of secondary amyloidosis is
      difficult and relies on systemic treatment. Colchicine may be helpful.

PMID- 14724540
TI  - [Trigeminal neuralgia presenting as a deep recurrent desmoplastic neurotropic
      melanoma of a lentigo maligna].
AB  - INTRODUCTION: Neurotropic melanoma is a particular anatomopathological form
      corresponding to dermal proliferation of desmoplastic cells of neuroid
      differentiation. We report a new case of neurotropic melanoma revealed by facial
      neuralgia. CASE REPORT: A 64 year-old man presented in 1996 with a lentigo
      maligna on the right cheek treated by complete excision. After 2 years of medical
      supervision, a pigmented lesion recurred leading to new surgical treatment. The
      histological examination of the total lesion showed intra-epidermal atypical
      melanocyte proliferation without dermal invasion. In 1999, right trigeminal
      neuralgia occurred without associated cutaneous change. Cranial MRI revealed an
      infiltration of the right trigeminal nerve. Endo-buccal surgery disclosed a black
      swelling of the trigeminal nerve. Histological examination and
      immunohistochemistry revealed a desmoplastic melanoma. DISCUSSION: Neurotropic
      melanoma with nerve invasion by malignant cells presenting as a trigeminal
      neuralgia is rare. Our case report underlined the depth of the neurotropic
      melanoma and the initial existence of a lentigo maligna without associated
      "neurotropic" melanoma.

PMID- 14724541
TI  - [Atrophic involution of juvenile xanthogranulomas].
AB  - INTRODUCTION: We report an unusual atrophic involution of juvenile
      xanthogranulomas. CASE REPORT: A newborn boy presented with 5 papular, nodular
      and necrotic lesions located on the upper part of the body. The diameter of the
      lesions ranged between 1 and 3 cm. Light microscopy showed an infiltrate with
      foamy and Touton cells. Langerhans' cell histiocytosis was eliminated because
      none of these cells showed reactivity for S100 protein and CD1a. At the age of 8
      years, all the lesions had spontaneously regressed leaving unusual atrophic scars
      that had the same size as the active lesions. DISCUSSION: We compared the
      clinical, histological and evolution data of our patient with 251 published
      cases. The most significant clinical feature of juvenile xanthogranuloma is the
      spontaneous involution without any trace. However, hyperpigmentation, anetoderma
      or atrophy may occur. Atrophy is not frequent and can result from 2 mechanisms.
      Inflammation of the hypodermic tissue, which becomes atrophic and atrophy that
      may also result from collagen remodeling anomalies during the scarring process.

PMID- 14724542
TI  - [Severe cutaneous drug reactions to celecoxib (Celebrex)].
AB  - INTRODUCTION: Celecoxib (Celebrex) is a Cox 2 selective non steroidal anti
      inflammatory agent. Adverse reactions reported are usually benign, such as
      maculopapular exanthema. However, recently severe toxiderma have started to
      appear. We report two patients who developed a sever celecoxib drug skin
      reaction. OBSERVATIONS: Case no 1. In a 73 year-old woman, treated with celecoxib
      for cervical arthralgia, a maculopapular exanthema five days after treatment was
      started. The exanthema, initially edematous and purpural became bullous with
      multi-visceral failure (disseminated intravascular coagulation, renal failure,
      hepatitis and pancreatic). The disease slowly regressed. Case no 2. A 72 year-old
      man, treated for cervicalgia with celecoxib, presented a pustular exanthema of
      the face and the trunk, ten days after introduction of the treatment, associated
      with an inflammatory syndrome and hepatic cytolysis. Within 8 days the disease
      had regressed. In both these patients, the celecoxib patch tests were positive.
      DISCUSSION: Until now, the side effects reported with celecoxib have been
      generally benign exanthemas. We report two cases of severe celecoxib-induced
      toxiderma: a hypersensitivity syndrome with multi-organ failure and an acute
      generalized atypical exanthematous pustulosis. These severe toxidermas have
      rarely been reported in the literature, but we now need to reassess the risks
      with these new molecules.

PMID- 14724543
TI  - [Liposomal doxorubicin and palmoplantar erythrodysesthesia].

PMID- 14724544
TI  - [Bullous eruption after influenza virus vaccination].

PMID- 14724545
TI  - [A necrotic plaque on the thigh].

PMID- 14724546
TI  - [Intertrigo resistant to treatment].

PMID- 14724547
TI  - [Sebaceous hamartoma].

PMID- 14724548
TI  - [Skin stem cells].

PMID- 14724549
TI  - [Parasitological exploration of the feces].

PMID- 14724550
TI  - [Odds ratio and relative risk].

PMID- 14724552
TI  - [Bejel].

PMID- 14724554
TI  - [Adrien Doyon (1827-1907). Creator of the Annals, but also well-known
      balneologist and European scholar].

PMID- 14724555
TI  - [A campaign supported by the International Dermatology Foundation: the pilot
      program in the fight against current skin diseases in Mali].

PMID- 14724556
TI  - Applying public health strategies to primary immunodeficiency diseases: a
      potential approach to genetic disorders.
AB  - Primary immunodeficiency (PI) diseases are a group of primarily single-gene
      disorders of the immune system. Approximately 100 separate PI diseases have been
      described, but <20 probably account for >90% of cases. Although diverse, PI
      diseases share the common feature of susceptibility to infection and result in
      substantial morbidity and shortened life spans. Most important, prompt diagnosis
      and treatment can now lead to life-saving treatment and result in marked
      improvements in the quality and length of life for persons with PI diseases. In
      November 2001, a workshop was convened by CDC in Atlanta, Georgia, to discuss
      ways to improve health outcomes among persons with PI disease. A
      multidisciplinary panel of persons knowledgeable in PI diseases and public health
      met to identify and discuss public health strategies that can be applied to PI
      diseases and possibly for other genetic disorders. A systematic assessment based
      on the established public health framework was applied to the growing group of PI
      diseases, whose diverse genetic mutations span multiple components of the immune
      system but all lead to increased incidence and severity of infections. During the
      meeting, specialists in clinical immunology, public health, genetics, pediatrics,
      health communication, and ethics from state and federal agencies, academic
      centers, professional organizations, and advocacy foundations discussed the four
      components of the public health framework as they relate to PI diseases. These
      four components include 1) public health assessment (application of traditional
      public health methods to assess the occurrence and impact of PI diseases on
      communities); 2) population-based interventions (development, implementation, and
      evaluation of screening tests administered to newborns and clinical algorithms
      for early recognition of symptomatic persons to facilitate the earliest possible
      diagnosis and treatment for PI diseases); 3) evaluation of screening and
      diagnostic tools (to ensure their quality and appropriateness for identification
      of patients with PI diseases); and 4) communication (communication with and
      information dissemination to health-care providers and the public to facilitate
      prompt and appropriate diagnosis and intervention). The working group's
      deliberations focused on challenges and opportunities, priority research
      questions, and recommendations for future action for these four components. These
      recommendations, developed by workshop participants, will be useful to medical
      and public health professionals who are evaluating methods to increase
      recognition of PI diseases and other genetic disorders.

PMID- 14724557
TI  - Medical expenditures attributable to injuries--United States, 2000.
AB  - In the United States, injuries (i.e., unintentional and intentional) are the
      leading cause of death among persons aged <35 years and the fourth leading cause
      of death among persons of all ages. Injuries create a substantial burden on
      society in terms of medical resources used for treating and rehabilitating
      injured persons, productivity losses caused by morbidity and premature mortality,
      and pain and suffering of injured persons and their caregivers. To estimate
      annual injury-attributable medical expenditures in the United States, CDC
      analyzed data on injury prevalence and costs from the 2000 Medical Expenditure
      Panel Survey (MEPS) and the National Health Accounts (NHA). This report
      summarizes the results of that analysis, which indicated that injury-attributable
      medical expenditures cost as much as 117 billion dollars in 2000, approximately
      10% of total U.S. medical expenditures. This finding underscores the need for
      innovative and effective interventions to prevent injuries.

PMID- 14724558
TI  - Declining prevalence of no known major risk factors for heart disease and stroke
      among adults--United States, 1991-2001.
AB  - Despite declines in recent years, heart disease and stroke remain the first and
      third leading causes of death in the United States, respectively. Of all U.S.
      deaths in 2001, heart disease accounted for 29.0% and stroke for 6.8%. The major
      risk factors for both conditions are high blood pressure, high cholesterol,
      diabetes, smoking, and obesity, all of which have been targeted by national
      prevention programs. In addition, the prevalence of multiple major risk factors
      has been a matter of increasing concern. However, few studies of national and
      state-level data have examined the prevalence of no known major risk factors
      among adults and how that prevalence has changed during the preceding 10 years.
      To assess changes in prevalence of no known risk factors for heart disease and
      stroke during 1991-2001, CDC analyzed data from the Behavioral Risk Factor
      Surveillance System (BRFSS). This report summarizes the results of that analysis,
      which indicate that prevalence of no known major risk factors is decreasing among
      men and women in nearly all states, racial/ethnic populations, age groups, and
      education levels. In addition, the prevalence of individual major risk factors is
      increasing. These findings underscore the potential for an increased burden of
      heart disease and stroke on the health-care system. To prevent the debilitating
      outcomes of heart disease and stroke among the aging U.S. population, increased
      prevention efforts and treatment interventions are needed.

PMID- 14724559
TI  - Preliminary assessment of the effectiveness of the 2003-04 inactivated influenza
      vaccine--Colorado, December 2003.
AB  - Influenza activity started earlier than usual in the United States this season,
      with widespread influenza activity reported in 10 states by November 22, 2003.
      The predominant influenza viruses (A/Fujian/411/2002 [H3N2]-like viruses)
      circulating this season differ antigenically from the 2003-04 influenza A (H3N2)
      vaccine strain. A retrospective cohort study was conducted among workers at a
      Colorado hospital to provide preliminary data on the effectiveness of trivalent
      inactivated influenza vaccine (TIV) against influenza-like illness (ILI). This
      report summarizes the results of that study, which indicated that TIV had no or
      low effectiveness against ILI. However, additional studies are needed to evaluate
      the effectiveness of the 2003-04 vaccine against laboratory-confirmed influenza
      and influenza-related complications, including hospitalization and death.
      Influenza vaccine continues to be recommended, particularly for persons at
      increased risk for influenza-related complications, their household contacts, and
      health-care personnel.

PMID- 14724560
TI  - Update: influenza activity--United States, January 4-10, 2004.
AB  - The number of states reporting widespread influenza activity continued to
      decrease during the reporting week of January 4-10, 2004. Health departments in
      20 states and New York City reported widespread influenza activity. A total of 24
      states reported regional activity, three states reported local activity, and
      sporadic activity was reported by two states, the District of Columbia, Guam, and
      Puerto Rico. The percentage of outpatient visits for influenza-like illness (ILI)
      continued to decrease in all surveillance regions during the week ending January
      10, with an overall national percentage of 2.8%. This percentage is above the
      national baseline of 2.5%. The percentage of specimens testing positive for
      influenza also decreased; however, the percentage of deaths attributed to
      pneumonia and influenza (P&I) continued to increase.

PMID- 14724562
TI  - Transmembrane proteases in cell growth and invasion: new contributors to
      angiogenesis?
AB  - Transmembrane proteases (TPs) are proteins anchored in the plasma membrane with
      their catalytic site exposed to the external surface of the membrane. TPs are
      widely expressed, and their dysregulated expression is associated with cancer,
      infection, inflammation, autoimmune and cardiovascular diseases, all diseases
      where angiogenesis is part of the pathology. TPs participate in extracellular
      proteolysis (degradation of extracellular matrix components, regulation of
      chemokine activity, release of membrane-anchored cytokines, cytokine receptors
      and adhesion molecules) and influence cell functions (growth, secretion of
      angiogenic molecules, motility). Recent attention has been focused on the ADAM-17
      (a disintegrin and metalloprotease)/TACE/CD156q, the MT1-MMP (membrane-type-1
      matrix metallo proteinase)/MMP-14, and the ectopeptidases aminopeptidase N
      (APN/CD13), dipeptidyl peptidase IV (DPPIV/CD26) and angiotensin-converting
      enzyme (ACE/CD143), that appear to have a critical role in angiogenesis. This
      article summarizes current knowledge on these TPs, and reviews recent
      investigations that document their participation during angiogenic-related
      events. Through their multiple roles, TPs may thereby provide critical links in
      angiogenesis.

PMID- 14724563
TI  - E6/E7 proteins of HPV type 16 and ErbB-2 cooperate to induce neoplastic
      transformation of primary normal oral epithelial cells.
AB  - Head and neck squamous cell carcinomas (HNSCC) are characterized by a marked
      propensity for local invasion and spread to cervical lymph nodes, with distant
      metastases developing in 30-40% of cases. HPV-16 is an important risk factor for
      HNSCC. How HPV enhances susceptibility to HNSCC is not fully understood, but
      seems to involve cofactors. In this study, we examined the effect of the
      cooperation between HPV-16 and the tyrosine kinase receptor ErbB-2 on E
      cadherin/catenin complex patterns and neoplastic transformation of human normal
      oral epithelial (NOE) cells. We report that overexpression of ErbB-2 or E6/E7
      alone does not affect E-cadherin/catenin complex patterns nor does it induce cell
      transformation of NOE cells. In contrast, coexpression of E6/E7 and ErbB-2
      downregulates E-cadherin and catenin expression. This is accompanied by
      cytoplasmic localization of E-cadherin, as well as nuclear translocation of
      alpha, beta, and gamma-catenins. Furthermore, we demonstrate that E6/E7 cooperate
      with overexpressed ErbB-2 to induce tumor formation in nude mice and to
      upregulate cyclin D1 and c-myc expression. Our data suggest that E6/E7 cooperate
      with ErbB-2 in head and neck carcinogenesis, at least in part, via the conversion
      of beta-catenin from a cell adhesion to a nuclear function, that is, to act as a
      potential transcriptional regulator. This conversion leads to the upregulation of
      cyclin D1, c-myc and other oncoproteins necessary for alteration of the E
      cadherin/catenin complex and cell transformation of NOE cells.

PMID- 14724564
TI  - Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires
      DNA replication and is mediated by p53 and Fas/CD95/Apo-1.
AB  - Various tumor-therapeutic drugs and environmental carcinogens alkylate DNA
      inducing O(6)-methylguanine (O(6)MeG) that provokes cell death by apoptosis. In
      rodent fibroblasts, apoptosis triggered by O(6)MeG is executed via the
      mitochondrial damage pathway. Conversion of O(6)MeG into critical downstream
      lesions requires mismatch repair (MMR). This is thought to signal apoptosis upon
      binding to O(6)MeG lesions mispaired with thymine. Alternatively, O(6)MeG lesions
      might be processed by MMR giving rise to DNA double-strand breaks (DSBs) during
      replication that finally provoke apoptosis. To test this, we examined apoptosis
      triggered by O(6)MeG in human peripheral lymphocytes in which O(6)-methylguanine
      DNA methyltransferase (MGMT) had been inactivated by O(6)-benzylguanine (O(6)BG)
      and which were not proliferating or proliferating upon CD3/CD28 stimulation.
      Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or the anticancer drug
      temozolomide induced apoptosis only in proliferating, but not resting cells. With
      exceptional high alkylation doses (>/=15 microM of MNNG), apoptosis was also
      observed in resting lymphocytes, albeit at a lower level than in proliferating
      cells. This response was not affected by O(6)BG, suggesting that replication
      independent apoptosis at high dose levels is caused by lesions other than
      O(6)MeG. O(6)MeG-triggered apoptosis in proliferating lymphocytes was preceded by
      a wave of DSBs, which coincided with p53 and Fas receptor upregulation, while Fas
      ligand, Bax and Bcl-2 expression was not altered. Treatment with anti-Fas
      neutralizing antibody attenuated MNNG-induced apoptosis in MGMT-depleted
      proliferating lymphocytes. The data suggest that O(6)MeG is converted by MMR and
      DNA replication into DSBs that trigger apoptosis by p53 stabilization and
      Fas/CD95/Apo-1 upregulation. This is supported by the finding that ionizing
      radiation, inducing DSBs on its own, provokes apoptosis in lymphocytes in a
      replication-independent way. The strict proliferation dependence of apoptosis
      triggered by O(6)MeG may explain the specific killing response of MGMT-deficient
      proliferating cells, including tumors, to O(6)MeG generating anticancer drugs and
      suggests that tumor proliferation rate, Fas responsiveness, MGMT and MMR status
      are important prognosis parameters.

PMID- 14724565
TI  - Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann
      cells.
AB  - The neurofibromatosis type 1 tumor suppressor protein neurofibromin, is a GTPase
      activating protein for H-, N-, K-, R-Ras and TC21/R-Ras2 proteins. We demonstrate
      that Schwann cells derived from Nf1-null mice have enhanced chemokinetic and
      chemotactic migration in comparison to wild-type controls. Surprisingly, this
      migratory phenotype is not inhibited by a farnesyltransferase inhibitor or
      dominant-negative (dn) (N17)H-Ras (which inhibits H-, N-, and K-Ras activation).
      We postulated that increased activity of R-Ras and/or TC21/R-Ras2, due to loss of
      Nf1, contributes to increased migration. Mouse Schwann cells (MSCs) express R-Ras
      and TC21/R-Ras2 and their specific guanine exchange factors, C3G and AND-34.
      Infection of Nf1-null MSCs with a dn(43N)R-Ras adenovirus (to inhibit both R-Ras
      and TC21/R-Ras2 activation) decreases migration by approximately 50%. Conversely,
      expression of activated (72L)TC21/R-Ras2, but not activated (38V)R-Ras, increases
      migration, suggesting a role of TC21/R-Ras2 activation in the migration of
      neurofibromin-deficient Schwann cells. TC21/R-Ras2 preferentially couples to the
      phosphatidylinositol 3-kinase (PI3-kinase) and MAP kinase pathways. Treatment
      with a PI3-kinase or MAP kinase inhibitor reduces Nf1-null Schwann cell
      migration, implicating these TC21 effectors in Schwann cell migration. These data
      reveal a key role for neurofibromin regulation of TC21/R-Ras2 in Schwann cells, a
      cell type critical to NF1 tumor pathogenesis.

PMID- 14724566
TI  - The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and
      tumorigenesis.
AB  - Mounting genetic evidence suggests that each product of the Ink4a/Arf locus,
      p16(INK4a) and p19(ARF), possesses tumor-suppressor activity (Kamijo et al.,
      1997; Krimpenfort et al., 2001; Sharpless et al., 2001a). We report the
      generation and characterization of a p19(ARF)-specific knockout allele (p19(ARF)
      /-) and direct comparison with mice and derivative cells deficient for
      p16(INK4a), both p16(INK4a) and p19(ARF), and p53. Like Ink4a/Arf-/- murine
      embryo fibroblasts (MEFs), p19(ARF)-/- MEFs were highly susceptible to oncogenic
      transformation, exhibited enhanced subcloning efficiency at low density, and
      resisted both RAS- and culture-induced growth arrest. In contrast, the biological
      profile of p16(INK4a)-/- MEFs in these assays more closely resembled that of wild
      type cells. In vivo, however, both p19(ARF)-/- and p16(INK4a)-/- animals were
      significantly more tumor prone than wild-type animals, but each less so than p53
      /- or Ink4a/Arf-/- animals, and with differing tumor spectra. These data confirm
      the predominant role of p19(ARF) over p16(INK4a) in cell culture-based assays of
      MEFs, yet also underscore the importance of the analysis of tumor suppressors
      across many cell types within the organism. The cancer-prone conditions of mice
      singly deficient for either p16(INK4a) or p19(ARF) agree with data derived from
      human cancer genetics, and reinforce the view that both gene products play
      significant and nonredundant roles in suppressing malignant transformation in
      vivo.

PMID- 14724567
TI  - Ribozyme-mediated inhibition of survivin expression increases spontaneous and
      drug-induced apoptosis and decreases the tumorigenic potential of human prostate
      cancer cells.
AB  - Survivin is a member of the inhibitor of apoptosis protein (IAP) family, which
      has been implicated in inhibition of apoptosis and control of mitotic
      progression. The finding that survivin is overexpressed in most human tumors but
      absent in normal adult tissues has led to the proposal of survivin as a promising
      therapeutic target for anticancer therapies. We decided to evaluate the effects
      of a ribozyme-based strategy for survivin inhibition in androgen-independent
      human prostate cancer cells. We constructed a Moloney-based retroviral vector
      expressing a ribozyme targeting the 3' end of the CUA(110) triplet in survivin
      mRNA, encoded as a chimeric RNA within adenoviral VA1 RNA. Polyclonal cell
      populations obtained by infection with the retroviral vector of two androgen
      independent human prostate cancer cell lines (DU145 and PC-3) were selected for
      the study. Ribozyme-expressing prostate cancer cells were characterized by a
      significant reduction of survivin expression compared to parental cells
      transduced with a control ribozyme; the cells became polyploid, underwent caspase
      9-dependent apoptosis and showed an altered pattern of gene expression, as
      detected by oligonucleotide array analysis. Survivin inhibition also increased
      the susceptibility of prostate cancer cells to cisplatin-induced apoptosis and
      prevented tumor formation when cells were xenografted in athymic nude mice. These
      findings suggest that manipulation of the antiapoptotic survivin pathway may
      provide a novel approach for the treatment of androgen-independent prostate
      cancer.

PMID- 14724568
TI  - Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in
      colorectal cancer.
AB  - Kruppel-like factor 4 (KLF4 or GKLF) is an inhibitor of the cell cycle. The gene
      encoding KLF4 is localized on chromosome 9q, previously shown to exhibit allelic
      loss in colorectal cancer (CRC). In this study, we show that the mean level of
      KLF4 mRNA in a panel of 30 CRC was 52% that of paired normal colonic tissues.
      Similarly, the levels of KLF4 mRNA and protein in a panel of six established CRC
      cell lines were significantly lower than those of an untransformed colonic
      epithelial cell line. Using highly polymorphic DNA markers that flank the KLF4
      locus, we found evidence for loss of heterozygosity (LOH) in two of eight
      surgically resected CRC specimens. In addition, LOH was observed in five of six
      CRC cell lines with one additional cell line exhibiting hemizygous deletion in
      the KLF4 gene. We also found that the 5'-untranslated region of KLF4 was
      hypermethylated in a subset of resected CRC specimens and cell lines. Lastly, the
      open-reading frame of KLF4 in two of three CRC cell lines examined contained
      several point mutations that resulted in a diminished ability to activate the
      p21(WAF1/Cip1) promoter. These findings indicate that KLF4 is a potential tumor
      suppressor gene in CRC.

PMID- 14724569
TI  - Coagulation factors VIIa and Xa inhibit apoptosis and anoikis.
AB  - The molecular mechanisms enabling cancer cells to survive loss-of-adhesion
      induced apoptosis in the early phases of metastasis remain largely obscure.
      Interestingly, the overexpression of tissue factor (TF) on tumor cells is
      associated with successful metastasis and it has now become clear that
      coagulation factor VIIa (FVIIa), the natural binding partner of TF induces signal
      transduction in TF-expressing cells. Hence, we investigated the effects of FVIIa
      TF interaction on cell survival. We observed that FVIIa, at physiologically
      relevant concentrations, inhibits cell death and caspase-3 activation induced by
      serum deprivation and loss of adhesion (lack of integrin signaling) in TF
      overexpressing cells, but not in non-TF-expressing cells. This FVIIa effect was
      not dependent on the formation of the downstream coagulation products FXa or
      thrombin and was inhibited using an active site-blocked form of FVIIa (FVIIai).
      FVIIa incubation resulted in the prolonged activation of both the
      phosphatidylinositide-3-(OH) kinase and p42/p44 MAP kinase pathways, and studies
      employing pharmacological inhibitors revealed that both the pathways are required
      for FVIIa-induced cell survival and inhibition of caspase-3 activity. Finally,
      TF:FVIIa-induced FXa generation dramatically increased cell survival. We propose
      that FVIIa-induced cell survival may explain why overexpression of TF is
      associated with successful metastasis.

PMID- 14724570
TI  - Wild-type p53 gene transfer is not detrimental to normal cells in vivo:
      implications for tumor gene therapy.
AB  - The p53 oncosuppressor is strictly maintained in an inactive form under normal
      conditions, while it is post-translationally activated by a variety of stresses,
      enacting different protective biological functions. Since one critical issue in
      cancer gene therapy is tumor specificity, we asked whether the tight p53
      regulation applies also to exogenously transferred p53. In principle, this type
      of regulation could allow p53 gene transfer in both normal and tumor cells to
      produce detrimental effects only in the latter ones. Here, we report that primary
      bone marrow cells infected with a p53 recombinant retrovirus and transplanted
      into irradiated mice reconstitute the hematopoietic system, with no detectable
      alterations in any of its compartments. Furthermore, simultaneous infection of
      leukemia and bone marrow cells depleted the neoplastic contamination, allowing
      lifelong, disease-free survival of 65% of the transplanted animals. These results
      show that exogenous p53 is controlled as tightly as the endogenous one, and opens
      the way to p53 gene therapy, without requiring tumor targeting.

PMID- 14724571
TI  - All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N
      terminal kinase in breast cancer cells.
AB  - Taxotere is a cytotoxin effective in treating breast and prostate cancer. It
      stabilizes microtubules and causes catastrophic cell cycle arrest in G2/M.
      Taxanes also initiate apoptosis by activating signal pathways, such as the jun N
      terminal kinase (JNK) pathway. Strategies aimed at potentiating cell death
      signaling may improve their efficacy while lessening the potential side effects.
      We reported that all-trans retinoic acid (ATRA) potentiated taxane-mediated cell
      death. Here we investigated whether ATRA potentiates cell death signaling through
      the JNK pathway. Activation of JNK by Taxotere 0.01, 0.1 and 1.0 microM was
      observed at 24 h in adherent cells and increased at 48 h. Taxotere 0.001 microM
      induced JNK activation started after 48 h and increased at 72 h. The timing and
      intensity of PARP cleavage was similar to that of JNK activation. JNK activation
      and PARP cleavage induced by 30 nM Taxotere at 48 h were reversed by curcumin,
      PD169316 and SP600125, JNK inhibitors in order of progressive specificity. None
      of these inhibitors had an effect on p38 or ERK phosphorylation. All three
      inhibitors reversed Taxotere-induced phosphorylation of Bcl-2. ATRA induced JNK
      activation at 24, 48 and 72 h. Incubating cells with ATRA 0.01 microM for 3 days
      prior to Taxotere treatment potentiated Taxotere-induced JNK activation 24 and 48
      h later, an effect sustained for 72 h. Cytotoxicities from 3-day ATRA 0.01 microM
      incubations were synergistic with subsequent 1-h Taxotere 0.01, 0.1 and 1.0
      microM incubations in breast cancer cell lines MCF-7 and MDA-MB-231 and in
      prostate cancer cell lines LNCaP and PC-3, and additive in breast cancer cell
      line SK-Br-3. These data demonstrate the potentiation of Taxotere-induced cell
      death by ATRA pretreatment in breast and prostate cancer cells, and support a
      mechanism through accentuated and sustained JNK activation.

PMID- 14724572
TI  - Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced
      activation of Cdc42 upstream of SAPK2/p38.
AB  - Activation of the tyrosine kinase receptor vascular endothelial growth factor
      receptor 2 (VEGFR2) by VEGF leads to the activation of stress-activated protein
      kinase (SAPK)2/p38 and then to actin polymerization and reorganization into
      stress fibers in endothelial cells. In turn, this triggers endothelial cell
      migration. Yet, nothing is known about the molecular mechanisms that couple
      VEGFR2 to SAPK2/p38. Here, we found that VEGF increased by twofold the activity
      of the small GTPase Cdc42 and that the expression of two different constitutively
      active forms of Cdc42 (Cdc42 V12 and Cdc42 L61) led to a marked increase in the
      formation of stress fibers that was sensitive to SAPK2/p38 inhibition by
      SB203580. Moreover, the expression of a dominant-negative form of Cdc42 (Cdc42
      N17) inhibited the activation of SAPK2/p38 and of its direct target MAP kinase
      activated protein kinase 2. These results indicate that Cdc42 is upstream of
      SAPK2/p38 in response to the activation of VEGFR2 by VEGF. In contrast, we found
      that neither RhoA nor Rac was involved in the SAPK2/p38-mediated actin
      reorganization induced by VEGF. Using a site-specific mutant of the major
      autophosphorylation site Y1214 on VEGFR2, we found that the mutant Y1214F
      inhibited the activation of both Cdc42 and SAPK2/p38 in response to VEGF. We
      conclude that phosphorylation of Y1214 on VEGFR2 is required to trigger the
      sequential activation of Cdc42 and SAPK2/p38 and to drive the SAPK2/p38-mediated
      actin remodeling in stress fibers in endothelial cells exposed to VEGF.

PMID- 14724573
TI  - Roscovitine sensitizes glioma cells to TRAIL-mediated apoptosis by downregulation
      of survivin and XIAP.
AB  - The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is limited in many glioma cell lines. However, treatment with
      TRAIL in combination with subtoxic doses of roscovitine, a specific inhibitor of
      Cdc2 and Cdk2, induced rapid apoptosis in TRAIL-resistant glioma cells.
      Roscovitine could sensitize Bcl-2- or Bcl-xL-overexpressing glioma cells, but not
      human astrocytes, to TRAIL-induced apoptosis, offering an attractive strategy for
      safely treating resistant gliomas. Treatment with roscovitine significantly
      inhibited Cdc2 activity, and expression of a dominant-negative Cdc2 mutant
      sensitized glioma cells to TRAIL-induced apoptosis. While the proteolytic
      processing of procaspase-3 by TRAIL was partially blocked in U87MG and T98 glioma
      cells, treatment with roscovitine recovered TRAIL-induced activation of caspases
      very efficiently in these cells. We found that treatment with roscovitine or
      expression of a dominant-negative Cdc2 mutant downregulated the protein levels of
      survivin and XIAP, two major caspase inhibitors. Overexpression of survivin or
      XIAP attenuated the apoptosis induced by roscovitine and TRAIL. Taken together,
      these results suggest that downregulation of survivin and XIAP by subtoxic doses
      of roscovitine contributes to the amplification of caspase cascades, thereby
      overcoming glioma cell resistance to TRAIL-mediated apoptosis.

PMID- 14724574
TI  - A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with
      potent.
AB  - Telomerase is a therapeutic target for cancer. Human telomerase reverse
      transcriptase (hTERT), the catalytic subunit of the telomerase, is
      transcriptionaly upregulated exclusively in about 90% of cancer cells. Previous
      studies have demonstrated that hTERT promoter can control the expression of
      exogenous genes to the telomerase-positive cancer cells, thus hTERT promoter is
      an excellent candidate for generating cancer-specific oncolytic adenovirus. In
      this study, we devised a novel oncolytic adenovirus (Ad.TERT) by replacing the
      normal E1A regulatory elements with hTERT promoter. Ad.TERT displays cancer
      specific E1A expression, virus replication and cytolysis in in vitro experiments.
      In animal experiments, intratumoral administration of Ad.TERT demonstrates potent
      antitumoral efficacy at least in two xenograft models (Bcap37 and BEL7404).
      Ad.TERT was targeted by the telomerase activity in cancer cells and has potent
      antitumoral efficacy in vivo, and since telomerase activity is a wide-ranged
      tumor marker, Ad.TERT could be a powerful therapeutic agent for a variety of
      cancers.

PMID- 14724575
TI  - CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability
      of pancreatic adenocarcinoma cells.
AB  - Anoikis is the apoptotic response induced in normal cells by inadequate or
      inappropriate adhesion to substrate. It is postulated that resistance to anoikis
      facilitates tumorigenesis and metastasis. Carcinoembryonic antigen-related cell
      adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily member
      overexpressed in a number of human cancers and implicated in anoikis resistance.
      We tested the effect of CEACAM6 gene silencing on anoikis in pancreatic
      adenocarcinoma cell lines. Anoikis was induced in PANC1, Capan2, MiaPaCa2 and
      Mia(AR) (a MiaPaCa2-derived anoikis-resistant subline) by culture in poly-2
      hydroxyethylmethacrylate-coated wells. Anoikis was quantified by YO-PRO
      1/propidium iodide staining and flow cytometry. The role of caspase activation
      was determined using fluorometric profiling and the caspase inhibitor Z-Val-Ala
      Asp-fluoromethyl ketone (Z-VAD-fmk). CEACAM6 expression was suppressed by RNA
      interference. Using a nude mouse orthotopic xenograft model, we assessed the
      effect of this treatment on in vivo metastatic ability. Anoikis resistance was
      associated with increased CEACAM6 expression. CEACAM6-specific short interfering
      ribonucleic acid (siRNA), but not control siRNA, increased susceptibility to
      caspase-mediated anoikis, an effect abrogated by Z-VAD-fmk, and decreased Akt
      phosphorylation (Ser-473) under anchorage-independent conditions. CEACAM6 gene
      silencing reversed the acquired anoikis resistance of Mia(AR) and inhibited its
      in vivo metastatic ability. CEACAM6 warrants further investigation as a novel
      therapeutic target for the treatment of pancreatic adenocarcinoma.

PMID- 14724576
TI  - Identification of a novel function of TWIST, a bHLH protein, in the development
      of acquired taxol resistance in human cancer cells.
AB  - Taxol is one of the widely used chemotherapeutic drugs against many types of
      human cancer. While it is considered as one of the most effective anticancer
      drugs, treatment failure often occurs due to development of acquired resistance.
      Therefore, it is important to understand the molecular mechanisms responsible for
      the development of drug resistance. Although it is generally believed that taxol
      induces cell death through interfering with microtubules leading to mitotic
      arrest, recent evidence has suggested that taxol-induced cell death also occurs
      through pathways independent of either microtubule or mitotic arrest. In this
      study, we report the identification of a novel role for TWIST, a basic helix-loop
      helix protein, which plays a central role in cell type determination and
      differentiation, during generation of acquired resistance to taxol in a
      nasopharyngeal carcinoma cell line, HNE1-T3, using comparative genome
      hybridization (CGH) and subsequent RT-PCR and Western blotting. We found that
      upregulation of TWIST was associated with cellular resistance to taxol but not
      other drugs with different mechanisms of action. The fact that increased TWIST
      protein levels were also associated with another microtubule-targeting anticancer
      drug, vincristine, in four types of human cancer including nasopharyngeal,
      bladder, ovarian and prostate, indicates that it may play a central role in the
      resistance to microtubule-disrupting agents. In addition, ectopic expression of
      TWIST into human cancer cells also led to increased resistance to both taxol and
      vincristine. Our results indicate a novel mechanism that leads to resistance to
      microtubule-disrupting anticancer drugs through upregulation of TWIST. Our
      evidence provides a therapeutic strategy to overcome acquired resistance through
      inactivation of TWIST expression in human cancer.

PMID- 14724577
TI  - Interaction between JCV large T-antigen and beta-catenin.
AB  - Expression of the JCV early protein T-antigen in transgenic mice leads to the
      development of cerebellar primitive neuroectodermal tumors (PNETs). In light of
      earlier reports on the association of JCV with PNETs in humans and the
      involvement of the Wnt signaling pathway in the development of cerebellar tumors,
      we investigated the interplay between T-antigen and beta-catenin, the key protein
      of the Wnt pathway. Our results demonstrate the physical interaction of T-antigen
      with beta-catenin through the central domain of T-antigen spanning residues 82
      628, and the C-terminus of beta-catenin located between amino acids 695 and 781.
      The association of T-antigen with beta-catenin elevates the level of beta-catenin
      in the cells due to increased in the stability of the protein. In the presence of
      T-antigen, beta-catenin was found in the nuclei of cells, suggesting that the
      interaction of beta-catenin with T-antigen facilitates its nuclear import. In
      cells expressing mutant T-antigen with no nuclear localization domain, beta
      catenin was found in the cytoplasm. Coexpression of T-antigen with beta-catenin
      increased the transcription of the c-myc promoter, a known downstream target of
      beta-catenin, and artificial promoter whose activity is beta-catenin dependent.
      These observations ascribe a new oncogenic pathway for T-antigen, and offer an
      alternative mechanism for the deregulation of the Wnt pathway through
      stabilization of beta-catenin upon its association with the viral oncoprotein.

PMID- 14724578
TI  - Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by
      p16(INK4a).
AB  - Through a screen aimed at identifying genes that are specifically upregulated in
      embryomic stem (ES) cells but not primitive ectoderm, we identified cyclin D3.
      This was surprising since cyclin D activity is generally believed to be inactive
      in ES cells even though retinoblastoma tumor suppressor protein (pRb) accumulates
      in a predominantly hyperphosphorylated state. Cdk6 is the major catalytic partner
      for cyclin D3 in ES cells and exhibits robust pRb kinase activity that is
      downregulated during the early stages of ES embryoid body differentiation. To
      investigate the basis underlying the insensitivity of ES cells to ectopic p16
      expression, we show that Cdk6-cyclin D3 complexes are not subject to inhibition
      by p16, similar to Cdk-viral cyclin complexes. These observations show that
      specificity exists between Cdk4/6-cyclin D complexes and their ability to be
      targeted by p16. Our data suggest that Cdk6-cyclin D3 activity in other cell
      types, including tumors, may also be refractory to p16-mediated growth inhibition
      and raises the possibility of additional specificity within the INK4 family.

PMID- 14724579
TI  - The KSHV G protein-coupled receptor signals via multiple pathways to induce
      transcription factor activation in primary effusion lymphoma cells.
AB  - Kaposi's sarcoma-associated virus (KSHV) is the causative agent of Kaposi's
      sarcoma (KS) and primary effusion lymphoma (PEL). The KSHV G protein-couple
      receptor (vGPCR) is a homologue of the human IL-8 receptor that signals
      constitutively, activates mitogen- and stress-activated kinases, and induces
      transcription via multiple transcription factors including AP-1 and NFkappaB.
      Furthermore, vGPCR causes cellular transformation in vitro and leads to KS-like
      tumors in transgenic mouse models. vGPCR has therefore become an exciting
      potential therapeutic target for KSHV-mediated disease, but its signaling
      properties need to be better understood in the context of KSHV-infected
      hematopoietic cells. We recently described a PEL cell line that expresses vGPCR
      via an inducible promoter and have shown that vGPCR has broad capabilities of
      affecting cellular and viral transcription patterns in this highly relevant cell
      type. To elucidate the predominant signaling pathways used by vGPCR in PEL cells,
      we have used reporter gene assays to measure vGPCR activity in the presence of
      various pharmacologic enzyme inhibitors and plasmid constructs. We show that
      vGPCR-induced activation of AP-1 and CREB is mediated cooperatively by a Gq-ERK
      1/2 and a Gi-PI3K-Src axis. Furthermore, unlike in other cell types, NFkappaB
      activation by vGPCR seems not to be substantially mediated by Gi or PI3K/Akt in
      PEL cells.

PMID- 14724580
TI  - Myostatin inhibits rhabdomyosarcoma cell proliferation through an Rb-independent
      pathway.
AB  - Rhabdomyosarcoma (RMS) tumors are the most common soft-tissue sarcomas in
      childhood. In this investigation, we show that myostatin, a skeletal muscle
      specific inhibitor of growth and differentiation is expressed and translated in
      the cultured RMS cell line, RD. The addition of exogenous recombinant myostatin
      inhibits the proliferation of RD cells cultured in growth media, consistent with
      the role of myostatin in normal myoblast proliferation inhibition. However,
      unlike normal myoblasts, upregulation of p21 was not observed. Rather, myostatin
      signalling resulted in the specific downregulation of both Cdk2 and its cognate
      partner, cyclin-E. The analysis of Rb reveals that there was no change in its
      phosphorylation status with myostatin treatment, consistent with D-type-cyclin
      Cdk4/6 complexes being active in the absence of p21. Moreover, the activity of Rb
      appeared to be unchanged between treated and nontreated RD cells, as determined
      by the ability of Rb to bind E2F1. The examination of NPAT, a substrate of cyclin
      E-Cdk2 involved in the transcriptional activation of replication-dependent
      histone gene expression, revealed that it undergoes a loss of phosphorylation
      with myostatin treatment. Supporting this, a downregulation in H4-histone gene
      expression was observed. These results suggest that myostatin could potentially
      be used as an inhibitor of RMS proliferation and define a previously
      uncharacterized, Rb-independent mechanism for the inhibition of muscle precursor
      cell proliferation by myostatin.

PMID- 14724581
TI  - Expression of ErbB2 enhances radiation-induced NF-kappaB activation.
AB  - Her-2/neu (ErbB2) oncogene, the second member of the epidermal growth factor
      receptor (EGFR) family, encodes a transmembrane tyrosine kinase receptor in Her-2
      positive tumors. Accumulating evidences demonstrate that signaling networks
      activated by EGFR and transcription factor NF-kappaB are associated with cell
      response to ionizing radiation (IR). The present study shows that overexpression
      of ErbB2 enhanced NF-kappaB activation induced by IR in human breast carcinoma
      MCF-7 cells transfected with ErbB2 genes (MCF-7/ErbB2). Stable transfection of
      dominant-negative mutant IkappaB (MCF-7/ErbB2/mIkappaB) or treatment with anti
      ErbB2 antibody, Herceptin, inhibited NF-kappaB activation and radiosensitized MCF
      7/ErbB2 cells. Consistent with NF-kappaB regulation, basal and IR-induced Akt, a
      kinase downstream of ErbB2, was activated in MCF-7/ErbB2 cells and inhibited by
      Herceptin. To identify specific genes affected by ErbB2-mediated NF-kappaB
      activation, a group of IR-responsive elements Cyclin B1, Cyclin D1, Bcl-2,
      Bcl/XL, BAD and BAX were evaluated. Basal levels of prosurvival elements Cyclin
      B1, Cyclin D1, Bcl-2 and Bcl/XL but not apoptotic BAD and BAX were upregulated in
      MCF-7/ErbB2 cells with striking enhancements in Bcl-2 and Bcl/XL. IR further
      induced Cyclin B1 and Cyclin D1 expression that was reduced by Herceptin. Bcl-2
      kept a high steady level after Herceptin+IR treatment and, in contrast to control
      MCF-7/Vector cells, Bcl/XL was inhibited in MCF-7/ErbB2 cells by Herceptin+IR
      treatment. However, all four prosurvival proteins were downregulated by
      inhibition of NF-kappaB in MCF-7/ErbB2/mIkappaB cells. These results thus provide
      evidence suggesting that overexpression of ErbB2 is able to enhance NF-kappaB
      response to IR, and that a specific prosurvival network downstream of NF-kappaB
      is triggered by treatments using anti-ErbB2 antibody combined with radiation.

PMID- 14724582
TI  - Rad51 overexpression promotes alternative double-strand break repair pathways and
      genome instability.
AB  - Genomic instability is characteristic of tumor cells, and a strong correlation
      exists between abnormal karyotype and tumorigenicity. Increased expression of the
      homologous recombination and DNA repair protein Rad51 has been reported in
      immortalized and tumor cells, which could alter recombination pathways to
      contribute to the chromosomal rearrangements found in these cells. We used a
      genetic system to examine the potential for multiple double-strand breaks to lead
      to genome rearrangements in the presence of increased Rad51 expression. Analysis
      of repair revealed a novel class of products consistent with crossing over,
      involving gene conversion associated with an exchange of flanking markers leading
      to chromosomal translocations. Increased Rad51 also promoted aneuploidy and
      multiple chromosomal rearrangements. These data provide a link between elevated
      Rad51 protein levels, genome instability, and tumor progression.

PMID- 14724583
TI  - Mutations of BRAF and KRAS2 in the development of Barrett's adenocarcinoma.
AB  - Activation of the Raf/MEK/ERK (MAPK) signal transduction cascade by RAS mutations
      has been found in a variety of human cancers. Mutations of BRAF provide an
      alternative route for activation of this signalling pathway. To determine the
      role of mutations in BRAF and KRAS2 in the neoplastic progression of Barrett's
      adenocarcinoma, we analysed both genes for common mutations. After
      microdissection, DNA of 19 Barrett's adenocarcinomas, 56 Barrett's
      intraepithelial neoplasias (n=29 low-grade intraepithelial neoplasia (LGIN) and
      n=27 high-grade intraepithelial neoplasia (HGIN)), 30 Barrett's mucosa without
      neoplasia and normal squamous, as well as gastric epithelium, were analysed for
      BRAF and KRAS2 mutation. Activating BRAF mutations were identified in 2/19
      Barrett's adenocarcinomas (11%) and in 1/27 HGIN (4%). KRAS2 mutations were found
      in four out of 19 (21%) Barrett's adenocarcinomas examined and in three cases of
      HGIN (11%). In LGIN as well as in normal gastric or oesophageal mucosa, neither
      BRAF nor KRAS2 mutations were detected. All lesions with KRAS2 mutations had an
      intact BRAF gene. The status of mismatch-repair proteins was neither related to
      BRAF nor KRAS2 mutations. These data indicate that RAS or BRAF mutations are
      detected in about 32% of all Barrett's adenocarcinomas. We conclude that the
      disruption of the Raf/MEK/ERK (MAPK) kinase pathway is a frequent but also early
      event in the development of Barrett's adenocarcinoma.

PMID- 14724584
TI  - The small GTP-binding protein, Rhes, regulates signal transduction from G protein
      coupled receptors.
AB  - The Ras homolog enriched in striatum, Rhes, is the product of a thyroid hormone
      regulated gene during brain development. Rhes and the dexamethasone-induced
      Dexras1 define a novel distinct subfamily of proteins within the Ras family,
      characterized by an extended variable domain in the carboxyl terminal region. We
      have carried this study because there is a complete lack of knowledge on Rhes
      signaling. We show that in PC12 cells, Rhes is targeted to the plasma membrane by
      farnesylation. We demonstrate that about 30% of the native Rhes protein is bound
      to GTP and this proportion is unaltered by typical Ras family nucleotide exchange
      factors. However, Rhes is not transforming in murine fibroblasts. We have also
      examined the role of Rhes in cell signaling. Rhes does not stimulate the ERK
      pathway. By contrast, it binds to and activates PI3K. On the other hand, we
      demonstrate that Rhes impairs the activation of the cAMP/PKA pathway by thyroid
      stimulating hormone, and by an activated beta2 adrenergic receptor by a mechanism
      that suggests uncoupling of the receptor to its cognate heterotrimeric complex.
      Overall, our results provide the initial insights into the role in signal
      transduction of this novel Ras family member.

PMID- 14724585
TI  - Both AML1 and EVI1 oncogenic components are required for the cooperation of
      AML1/MDS1/EVI1 with BCR/ABL in the induction of acute myelogenous leukemia in
      mice.
AB  - We have previously shown that BCR/ABL, a fusion protein generated by the
      t(9;22)(q34;q11) translocation found in the vast majority of chronic myelogenous
      leukemia (CML), cooperates with AML1/MDS1/EVI1 (AME), a fusion transcription
      factor generated by a t(3;21)(q26;q22) translocation identified as a secondary
      mutation in some cases of CML during the blast phase (CML-BC), in the rapid
      induction of an acute myelogenous leukemia (AML) in mice. In this study, we
      evaluated the leukemogenic potential of EVI1-, MDS1/EVI1- and AML1-related
      oncoproteins (AML1Delta, AML1/MDS1). We found that ectopic expression of either
      EVI1 or MDS1/EVI1 impaired hematopoiesis. However, neither EVI1 nor MDS1/EVI1 was
      sufficient for inducing AML in mice, although EVI1 did induce some hematologic
      neoplasia other than AML with a low efficiency. In addition, unlike AME, none of
      the EVI1- or AML1-related oncoproteins examined were capable of fully cooperating
      with BCR/ABL in the induction of AML. The results indicate that both the AML1 and
      EVI1 oncogenic components are required for the leukemogenic potential of AME and
      for the cooperation of AME and BCR/ABL in the induction of AML.

PMID- 14724586
TI  - Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function.
AB  - The neurofibromatosis 2 (NF2) tumor suppressor gene product, merlin, belongs to
      the ezrin-radixin-moesin (ERM) subgroup of the Protein 4.1 family, which links
      cell surface glycoproteins to the actin cytoskeleton. Previous studies have
      suggested that phosphorylation of merlin, similar to other ERM proteins, may
      regulate its function. To determine whether merlin phosphorylation has functional
      consequences for merlin suppression of cell growth and motility, we generated
      doxycycline-regulatable RT4 schwannoma cell lines that inducibly express full
      length merlin with mutations at two potential phosphorylation sites (amino-acid
      residues S518 and T576). Whereas a mutation at S518 that mimics constitutive
      phosphorylation (S518D) abrogates the ability of merlin to suppress cell growth
      and motility, the S518A merlin mutant, which mimics nonphosphorylated merlin,
      functions equivalently to wild-type merlin. Similar mutations involving T576, the
      analogous phosphorylation site in ERM proteins important for regulating their
      function, had no effect. In contrast to other functionally inactive missense
      merlin mutants, the regulated overexpression of S518D merlin resulted in dramatic
      changes in cell shape and the elaboration of filopodial extensions. These results
      provide the first direct demonstration that the S518D merlin mutation, which
      mimics merlin phosphorylation, impairs not only merlin growth and motility
      suppression but also leads to an acquisition of a novel phenotype previously
      ascribed to ERM proteins.

PMID- 14724587
TI  - Expression of the c-kit receptor characterizes a subset of neuroblastomas with
      favorable prognosis.
AB  - Expression of the c-kit proto-oncogene product in neuroblastomas has been
      reported, but its clinical relevance is unclear. We determined the expression of
      c-kit by immunohistochemistry in a series of 155 neuroblastomas with long-term
      follow-up. The specificity of the reaction was verified by Western blot analysis
      and quantitative RT-PCR, and exon 11 of the kit gene was screened for mutations
      by PCR and capillary electrophoresis. No mutations were detected, and
      transcription of the kit gene correlated with protein expression. c-kit
      expression was associated with lower tumor stages and a low rate of MYCN
      amplification. More importantly, it coincided with tumor differentiation
      (P<0.0001), and portended a favorable outcome with a relative risk of 0.18
      (P<0.0001). In a multivariate analysis of event-free survival, loss of c-kit
      (relative risk 4.25, P<0.0001) was an independent prognostic factor next to INSS
      stage 4 and before MYCN amplification. It is concluded that c-kit is
      transcriptionally regulated in neuroblastomas. Its expression likely identifies a
      subset of neuroblastomas with conserved capacity for differentiation, which may
      represent the embryonal variety of the disease. Assessment of c-kit may improve
      prognostic models for neuroblastoma and provide a basis for new therapy concepts.

PMID- 14724588
TI  - Inhibition of JNK reduces G2/M transit independent of p53, leading to
      endoreduplication, decreased proliferation, and apoptosis in breast cancer cells.
AB  - c-Jun N-terminal kinase (JNK) is activated by diverse cell stimuli, including
      stress, growth factors, and cytokines. Traditionally, activation of JNK by stress
      treatment is thought to induce cell death. However, our recent data indicate that
      JNK's ability to sensitize cells to apoptosis may be, in part, cell cycle
      dependent. Here, we show that the majority of both paclitaxel- and UV-induced
      apoptosis can be inhibited by the pharmacological JNK inhibitor, SP600125, in MCF
      7 cells. However, inhibition of JNK does little to reverse doxorubicin-induced
      apoptosis in MCF-7 cells or doxorubicin- and UV-mediated death in MDA MB-231
      cells. SP treatment causes G2/M arrest of three breast cancer cell lines and
      results in the endoreduplication (cellular DNA content >4N) of MCF-7 and MDA MB
      231 cells. These effects on cell cycle and apoptosis are not significantly
      altered by the inhibition of p53, indicating that JNK is functioning
      independently of p53. Lastly, inhibition of JNK using both SP and antisense
      oligonucleotides targeted to JNK1 and JNK2 reduced proliferation of all three
      breast cancer cell lines. Taken together, these results suggest that the
      activation of JNK is important for the induction of apoptosis following stresses
      that function at different cell cycle phases, and that basal JNK activity is
      necessary to promote proliferation and maintain diploidy in breast cancer cells.

PMID- 14724589
TI  - Elevated expression of PCGEM1, a prostate-specific gene with cell growth
      promoting function, is associated with high-risk prostate cancer patients.
AB  - PCGEM1 is a novel, highly prostate tissue-specific, androgen-regulated gene.
      Here, we demonstrate that PCGEM1 expression is significantly higher in prostate
      cancer (CaP) cells of African-American men than in Caucasian-American men
      (P=0.0002). Further, increased PCGEM1 expression associates with normal prostate
      epithelial cells of CaP patients with a family history of CaP (P=0.0400). PCGEM1
      overexpression in LNCaP and in NIH3T3 cells promotes cell proliferation and a
      dramatic increase in colony formation, suggesting a biological role of PCGEM1 in
      cell growth regulation. Taken together, the cell proliferation/colony formation
      promoting functions of PCGEM1 and the association of its increased expression
      with high-risk CaP patients suggest the potential roles of PCGEM1 in CaP
      onset/progression, especially in these high-risk groups.

PMID- 14724590
TI  - Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced
      proliferation and tumorigenicity of MDA-MB 435 cells.
AB  - SCC-S2/GG2-1/NDED is a recently discovered antiapoptotic molecule induced by the
      activation of the transcription factor NF-kappaB. Here we have examined a role of
      SCC-S2 in cell growth regulation in vitro and in vivo. Western blotting using an
      antipeptide antibody revealed endogenous SCC-S2 as a approximately 21 kDa
      cytosolic protein in human breast cancer cells (MDA-MB 231) and renal carcinoma
      cells (RCC-RS). The immunofluorescence detection method showed the cytosolic
      localization of FLAG-tagged human SCC-S2 in COS-1 transfectants. MDA-MB 435 human
      cancer cells stably transfected with the FLAG-tagged SCC-S2 cDNA exhibited
      increased growth rate as compared to control vector transfectants, as measured by
      the cell viability (>twofold; n=3; P<0.005) and thymidine-labeling procedures (
      approximately sixfold; n=3; P<0.0001). SCC-S2 transfectants also displayed an
      increase in cell migration in collagen I as compared to control transfectants (
      approximately twofold; n=3; P<0.005). In athymic mice, SCC-S2 transfectants
      showed significantly enhanced tumor growth as compared to control transfectants
      (mean tumor volumes, day 16: control, 56.86+/-19.82 mm(3); SCC-S2, 127.54+/-18.78
      mm(3); n=5; P<0.03). The examination of a limited number of clinical specimens
      revealed higher expression levels of SCC-S2 protein in certain human tumor
      tissues as compared to the matched normal adjacent tissues. Taken together, the
      present studies demonstrate SCC-S2 as a novel oncogenic factor in cancer cells.

PMID- 14724591
TI  - PTEN mutations are common in sporadic microsatellite stable colorectal cancer.
AB  - The tumour suppressor gene PTEN, located at chromosome sub-band 10q23.3, encodes
      a dual-specificity phosphatase that negatively regulates the phosphatidylinositol
      3'-kinase (PI3 K)/Akt-dependent cellular survival pathway. PTEN is frequently
      inactivated in many tumour types including glioblastoma, prostate and endometrial
      cancers. While initial studies reported that PTEN gene mutations were rare in
      colorectal cancer, more recent reports have shown an approximate 18% incidence of
      somatic PTEN mutations in colorectal tumours exhibiting microsatellite
      instability (MSI+). To verify the role of this gene in colorectal tumorigenesis,
      we analysed paired normal and tumour DNA from 41 unselected primary sporadic
      colorectal cancers for PTEN inactivation by mutation and/or allelic loss. We now
      report PTEN gene mutations in 19.5% (8/41) of tumours and allele loss, including
      all or part of the PTEN gene, in a further 17% (7/41) of the cases. Both PTEN
      alleles were affected in over half (9/15) of these cases showing PTEN genetic
      abnormalities. Using immunohistochemistry, we have further shown that all tumours
      harbouring PTEN alterations have either reduced or absent PTEN expression and
      this correlated strongly with later clinical stage of tumour at presentation
      (P=0.02). In contrast to previous reports, all but one of the tumours with PTEN
      gene mutations were microsatellite stable (MSI-), suggesting that PTEN is
      involved in a distinct pathway of colorectal tumorigenesis that is separate from
      the pathway of mismatch repair deficiency. This work therefore establishes the
      importance of PTEN in primary sporadic colorectal cancer.

PMID- 14724594
TI  - In praise of immigration.

PMID- 14724595
TI  - Don't fear the Robot Scientist.

PMID- 14724597
TI  - Plans resurrected to raise Venice above the encroaching sea.

PMID- 14724596
TI  - Robotic missions set to benefit as US takes aim at the Moon.

PMID- 14724598
TI  - Intelligence law draws fire over NSF security project.

PMID- 14724599
TI  - Europe warned against research council.

PMID- 14724600
TI  - Antibodies to SARS-like virus hint at repeated infections.

PMID- 14724601
TI  - India targets local HIV strain in test of AIDS vaccine.

PMID- 14724602
TI  - Neglected diseases brought in from the cold.

PMID- 14724603
TI  - National park's sale of creationist book draws geologists' ire.

PMID- 14724604
TI  - Sandpit initiative digs deep to bring disciplines together.

PMID- 14724605
TI  - Ethics accusations spark rapid reaction from NIH chief.

PMID- 14724608
TI  - As one door closes...

PMID- 14724609
TI  - Scandals stem from the low priority of peer review.

PMID- 14724610
TI  - Eastern Europe: progress stifled by the old guard.

PMID- 14724611
TI  - Eastern Europe needs a competitive atmosphere.

PMID- 14724616
TI  - Tumour suppression: putting on the brakes.

PMID- 14724617
TI  - Immunology: protein surgery.

PMID- 14724618
TI  - Condensed-matter physics: supersolid helium.

PMID- 14724619
TI  - Palaeontology: lost children of the Cambrian.

PMID- 14724621
TI  - Astronomy: star maker.

PMID- 14724622
TI  - Earth science: keeping score on the core.

PMID- 14724623
TI  - Evolutionary biology: our relative genetics.

PMID- 14724625
TI  - Archaeology: a lion found in the Egyptian tomb of Maia.
AB  - Lions are mentioned by classical scholars and in pharaonic inscriptions as being
      among the sacred animals that were bred and buried in the Nile valley. And yet no
      specimens have been found in Egypt - until the excavation of the Bubasteion
      necropolis at Saqqara. Here we describe a complete skeleton, once a mummy, of a
      male lion (Panthera leo) that was discovered there, buried among the cats'
      catacombs created during the last centuries bc and occupying the much older tomb
      of Maia, wet-nurse to the king Tutankhamun (from the New Kingdom, fourteenth
      century bc). This important find at a site that was dedicated to the feline
      goddess Bastet (also known as Bubastis) confirms the status of the lion as a
      sacred animal during the Late and Greek periods.

PMID- 14724626
TI  - Olfaction: mosquito receptor for human-sweat odorant.
AB  - Female Anopheles mosquitoes, the world's most important vector of Plasmodium
      falciparum malaria, locate their human hosts primarily through olfactory cues,
      but the molecular mechanisms that underlie this recognition are a mystery. Here
      we show that the Anopheles gambiae protein AgOr1, a female-specific member of a
      family of putative odorant receptors, responds to a component of human sweat.
      Compounds designed to activate or block receptors of this type could function as
      attractants for trapping mosquitoes or as insect repellents in helping to control
      Anopheles and other insect pests.

PMID- 14724627
TI  - Climatology (communication arising): rural land-use change and climate.
AB  - Kalnay and Cai claim that urbanization and land-use change have a major effect on
      the climate in the United States. They used surface temperatures obtained from
      NCEP/NCAR 50-year reanalyses (NNR) and their difference compared with observed
      station surface temperatures as the basis for their conclusions, on the grounds
      that the NNR did not include these anthropogenic effects. However, we note that
      the NNR also overlooked other factors, such as known changes in clouds and in
      surface moisture, which are more likely to explain Kalnay and Cai's findings.
      Although urban heat-island effects are real in cities, direct estimates of the
      effects of rural land-use change indicate a cooling rather than a warming
      influence that is due to a greater reflection of sunlight.

PMID- 14724628
TI  - Climate (communication arising): impact of land-use change on climate.
AB  - Urbanization and other changes in land use have an impact on surface-air
      temperatures. Kalnay and Cai report that the observed surface-temperature trend
      in part of the United States exceeds the trend in the NCEP/NCAR 50-year
      reanalysis (NNR) and conclude that changes in land use account for the difference
      (0.035 degrees C per decade according to their corrected values). Although land
      use change may explain some of this discrepancy, the authors do not quantify the
      impact of the many changes in observational practice that occurred during the
      analysis period. Our findings indicate that these 'non-climatic' changes have a
      systematic effect that overwhelms the reported difference in trends and therefore
      calls Kalnay and Cai's central conclusion into question.

PMID- 14724630
TI  - Substrate twinning activates the signal recognition particle and its receptor.
AB  - Signal sequences target proteins for secretion from cells or for integration into
      cell membranes. As nascent proteins emerge from the ribosome, signal sequences
      are recognized by the signal recognition particle (SRP), which subsequently
      associates with its receptor (SR). In this complex, the SRP and SR stimulate each
      other's GTPase activity, and GTP hydrolysis ensures unidirectional targeting of
      cargo through a translocation pore in the membrane. To define the mechanism of
      reciprocal activation, we determined the 1.9 A structure of the complex formed
      between these two GTPases. The two partners form a quasi-two-fold symmetrical
      heterodimer. Biochemical analysis supports the importance of the extensive
      interaction surface. Complex formation aligns the two GTP molecules in a
      symmetrical, composite active site, and the 3'OH groups are essential for
      association, reciprocal activation and catalysis. This unique circle of twinned
      interactions is severed twice on hydrolysis, leading to complex dissociation
      after cargo delivery.

PMID- 14724631
TI  - An ultra-relativistic outflow from a neutron star accreting gas from a companion.
AB  - Collimated relativistic outflows-also known as jets-are amongst the most
      energetic phenomena in the Universe. They are associated with supermassive black
      holes in distant active galactic nuclei, accreting stellar-mass black holes and
      neutron stars in binary systems and are believed to be responsible for gamma-ray
      bursts. The physics of these jets, however, remains something of a mystery in
      that their bulk velocities, compositions and energetics remain poorly determined.
      Here we report the discovery of an ultra-relativistic outflow from a neutron star
      accreting gas within a binary stellar system. The velocity of the outflow is
      comparable to the fastest-moving flows observed from active galactic nuclei, and
      its strength is modulated by the rate of accretion of material onto the neutron
      star. Shocks are energized further downstream in the flow, which are themselves
      moving at mildly relativistic bulk velocities and are the sites of the observed
      synchrotron emission from the jet. We conclude that the generation of highly
      relativistic outflows does not require properties that are unique to black holes,
      such as an event horizon.

PMID- 14724632
TI  - Probable observation of a supersolid helium phase.
AB  - When liquid (4)He is cooled below 2.176 K, it undergoes a phase transition-Bose
      Einstein condensation-and becomes a superfluid with zero viscosity. Once in such
      a state, it can flow without dissipation even through pores of atomic dimensions.
      Although it is intuitive to associate superflow only with the liquid phase, it
      has been proposed theoretically that superflow can also occur in the solid phase
      of (4)He. Owing to quantum mechanical fluctuations, delocalized vacancies and
      defects are expected to be present in crystalline solid (4)He, even in the limit
      of zero temperature. These zero-point vacancies can in principle allow the
      appearance of superfluidity in the solid. However, in spite of many attempts,
      such a 'supersolid' phase has yet to be observed in bulk solid (4)He. Here we
      report torsional oscillator measurements on solid helium confined in a porous
      medium, a configuration that is likely to be more heavily populated with
      vacancies than bulk helium. We find an abrupt drop in the rotational inertia of
      the confined solid below a certain critical temperature. The most likely
      interpretation of the inertia drop is entry into the supersolid phase. If
      confirmed, our results show that all three states of matter-gas, liquid and solid
      can undergo Bose-Einstein condensation.

PMID- 14724633
TI  - Partial order in the non-Fermi-liquid phase of MnSi.
AB  - Only a few metallic phases have been identified in pure crystalline materials.
      These include normal, ferromagnetic and antiferromagnetic metals, systems with
      spin and charge density wave order, and superconductors. Fermi-liquid theory
      provides a basis for the description of all of these phases. It has been
      suggested that non-Fermi-liquid phases of metals may exist in some heavy-fermion
      compounds and oxide materials, but the discovery of a characteristic microscopic
      signature of such phases presents a major challenge. The transition-metal
      compound MnSi above a certain pressure (p(c) = 14.6 kbar) provides what may be
      the cleanest example of an extended non-Fermi-liquid phase in a three-dimensional
      metal. The bulk properties of MnSi suggest that long-range magnetic order is
      suppressed at p(c) (refs 7-12). Here we report neutron diffraction measurements
      of MnSi, revealing that sizeable quasi-static magnetic moments survive far into
      the non-Fermi-liquid phase. These moments are organized in an unusual pattern
      with partial long-range order. Our observation supports the existence of novel
      metallic phases with partial ordering of the conduction electrons (reminiscent of
      liquid crystals), as proposed for the high-temperature superconductors and heavy
      fermion compounds.

PMID- 14724634
TI  - Observational evidence of a change in radiative forcing due to the indirect
      aerosol effect.
AB  - Anthropogenic aerosols enhance cloud reflectivity by increasing the number
      concentration of cloud droplets, leading to a cooling effect on climate known as
      the indirect aerosol effect. Observational support for this effect is based
      mainly on evidence that aerosol number concentrations are connected with droplet
      concentrations, but it has been difficult to determine the impact of these
      indirect effects on radiative forcing. Here we provide observational evidence for
      a substantial alteration of radiative fluxes due to the indirect aerosol effect.
      We examine the effect of aerosols on cloud optical properties using measurements
      of aerosol and cloud properties at two North American sites that span polluted
      and clean conditions-a continental site in Oklahoma with high aerosol
      concentrations, and an Arctic site in Alaska with low aerosol concentrations. We
      determine the cloud optical depth required to fit the observed shortwave downward
      surface radiation. We then use a cloud parcel model to simulate the cloud optical
      depth from observed aerosol properties due to the indirect aerosol effect. From
      the good agreement between the simulated indirect aerosol effect and observed
      surface radiation, we conclude that the indirect aerosol effect has a significant
      influence on radiative fluxes.

PMID- 14724635
TI  - Tungsten isotope evidence that mantle plumes contain no contribution from the
      Earth's core.
AB  - Osmium isotope ratios provide important constraints on the sources of ocean
      island basalts, but two very different models have been put forward to explain
      such data. One model interprets (187)Os-enrichments in terms of a component of
      recycled oceanic crust within the source material. The other model infers that
      interaction of the mantle with the Earth's outer core produces the isotope
      anomalies and, as a result of coupled (186)Os-(187)Os anomalies, put time
      constraints on inner-core formation. Like osmium, tungsten is a siderophile
      ('iron-loving') element that preferentially partitioned into the Earth's core
      during core formation but is also 'incompatible' during mantle melting (it
      preferentially enters the melt phase), which makes it further depleted in the
      mantle. Tungsten should therefore be a sensitive tracer of core contributions in
      the source of mantle melts. Here we present high-precision tungsten isotope data
      from the same set of Hawaiian rocks used to establish the previously interpreted
      (186)Os-(187)Os anomalies and on selected South African rocks, which have also
      been proposed to contain a core contribution. None of the samples that we have
      analysed have a negative tungsten isotope value, as predicted from the core
      contribution model. This rules out a simple core-mantle mixing scenario and
      suggests that the radiogenic osmium in ocean-island basalts can better be
      explained by the source of such basalts containing a component of recycled crust.

PMID- 14724636
TI  - Fossil embryos from the Middle and Late Cambrian period of Hunan, south China.
AB  - Comparative embryology is integral to uncovering the pattern and process of
      metazoan phylogeny, but it relies on the assumption that life histories of living
      taxa are representative of their antecedents. Fossil embryos provide a crucial
      test of this assumption and, potentially, insight into the evolution of
      development, but because discoveries so far lack phylogenetic constraint, their
      significance is moot. Here we describe a collection of embryos from the Middle
      and Late Cambrian period (500 million years ago) of Hunan, south China, that
      preserves stages of development from cleavage to the pre-hatching embryo of a
      direct-developing animal comparable to living Scalidophora (phyla Priapulida,
      Kinorhyncha, Loricifera). The latest-stage embryos show affinity to the Lower
      Cambrian embryo Markuelia, whose life-history strategy contrasts both with the
      primitive condition inferred for metazoan phyla and with many proposed hypotheses
      of affinity, all of which prescribe indirect development. Phylogenetic tests
      based on these embryological data suggest a stem Scalidophora affinity. These
      discoveries corroborate, rather than contradict, the predictions of comparative
      embryology, providing direct historical support for the view that the life
      history strategies of living taxa are representative of their stem lineages.

PMID- 14724637
TI  - Whole-lake carbon-13 additions reveal terrestrial support of aquatic food webs.
AB  - Ecosystems are supported by organic carbon from two distinct sources. Endogenous
      carbon is produced by photosynthesis within an ecosystem by autotrophic
      organisms. Exogenous carbon is produced elsewhere and transported into
      ecosystems. Consumers may use exogenous carbon with consequent influences on
      population dynamics, predator-prey relationships and ecosystem processes. For
      example, exogenous inputs provide resources that may enhance consumer abundance
      beyond levels supported by within-system primary production. Exogenous fluxes of
      organic carbon to ecosystems are often large, but this material is recalcitrant
      and difficult to assimilate, in contrast to endogenously produced organic matter,
      which is used more easily. Here we show, by the experimental manipulation of
      dissolved inorganic (13)C in two lakes, that internal primary production is
      insufficient to support the food webs of these ecosystems. Additions of
      NaH(13)CO(3) enriched the (13)C content of dissolved inorganic carbon,
      particulate organic carbon, zooplankton and fish. Dynamics of (13)C indicate that
      40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived
      from terrestrial sources, showing that there is significant subsidy of these
      ecosystems by organic carbon produced outside their boundaries.

PMID- 14724638
TI  - Bayesian integration in sensorimotor learning.
AB  - When we learn a new motor skill, such as playing an approaching tennis ball, both
      our sensors and the task possess variability. Our sensors provide imperfect
      information about the ball's velocity, so we can only estimate it. Combining
      information from multiple modalities can reduce the error in this estimate. On a
      longer time scale, not all velocities are a priori equally probable, and over the
      course of a match there will be a probability distribution of velocities.
      According to bayesian theory, an optimal estimate results from combining
      information about the distribution of velocities-the prior-with evidence from
      sensory feedback. As uncertainty increases, when playing in fog or at dusk, the
      system should increasingly rely on prior knowledge. To use a bayesian strategy,
      the brain would need to represent the prior distribution and the level of
      uncertainty in the sensory feedback. Here we control the statistical variations
      of a new sensorimotor task and manipulate the uncertainty of the sensory
      feedback. We show that subjects internally represent both the statistical
      distribution of the task and their sensory uncertainty, combining them in a
      manner consistent with a performance-optimizing bayesian process. The central
      nervous system therefore employs probabilistic models during sensorimotor
      learning.

PMID- 14724639
TI  - Functional genomic hypothesis generation and experimentation by a robot
      scientist.
AB  - The question of whether it is possible to automate the scientific process is of
      both great theoretical interest and increasing practical importance because, in
      many scientific areas, data are being generated much faster than they can be
      effectively analysed. We describe a physically implemented robotic system that
      applies techniques from artificial intelligence to carry out cycles of scientific
      experimentation. The system automatically originates hypotheses to explain
      observations, devises experiments to test these hypotheses, physically runs the
      experiments using a laboratory robot, interprets the results to falsify
      hypotheses inconsistent with the data, and then repeats the cycle. Here we apply
      the system to the determination of gene function using deletion mutants of yeast
      (Saccharomyces cerevisiae) and auxotrophic growth experiments. We built and
      tested a detailed logical model (involving genes, proteins and metabolites) of
      the aromatic amino acid synthesis pathway. In biological experiments that
      automatically reconstruct parts of this model, we show that an intelligent
      experiment selection strategy is competitive with human performance and
      significantly outperforms, with a cost decrease of 3-fold and 100-fold
      (respectively), both cheapest and random-experiment selection.

PMID- 14724640
TI  - Immune recognition of a human renal cancer antigen through post-translational
      protein splicing.
AB  - Cytotoxic T lymphocytes (CTLs) detect and destroy cells displaying class I
      molecules of the major histocompatibility complex (MHC) that present
      oligopeptides derived from aberrant self or foreign proteins. Most class I
      peptide ligands are created from proteins that are degraded by proteasomes and
      transported, by the transporter associated with antigen processing, from the
      cytosol into the endoplasmic reticulum, where peptides bind MHC class I molecules
      and are conveyed to the cell surface. C2 CTLs, cloned from human CTLs
      infiltrating a renal cell carcinoma, kill cancer cells overexpressing fibroblast
      growth factor-5 (FGF-5). Here we show that C2 cells recognize human leukocyte
      antigen-A3 MHC class I molecules presenting a nine-residue FGF-5 peptide
      generated by protein splicing. This process, previously described strictly in
      plants and unicellular organisms, entails post-translational excision of a
      polypeptide segment followed by ligation of the newly liberated carboxy-terminal
      and amino-terminal residues. The occurrence of protein splicing in vertebrates
      has important implications for the complexity of the vertebrate proteome and for
      the immune recognition of self and foreign peptides.

PMID- 14724641
TI  - Ras regulates assembly of mitogenic signalling complexes through the effector
      protein IMP.
AB  - The signal transduction cascade comprising Raf, mitogen-activated protein (MAP)
      kinase kinase (MEK) and MAP kinase is a Ras effector pathway that mediates
      diverse cellular responses to environmental cues and contributes to Ras-dependent
      oncogenic transformation. Here we report that the Ras effector protein Impedes
      Mitogenic signal Propagation (IMP) modulates sensitivity of the MAP kinase
      cascade to stimulus-dependent activation by limiting functional assembly of the
      core enzymatic components through the inactivation of KSR, a scaffold/adaptor
      protein that couples activated Raf to its substrate MEK. IMP is a Ras-responsive
      E3 ubiquitin ligase that, on activation of Ras, is modified by auto
      polyubiquitination, which releases the inhibition of Raf-MEK complex formation.
      Thus, Ras activates the MAP kinase cascade through simultaneous dual effector
      interactions: induction of Raf kinase activity and derepression of Raf-MEK
      complex formation. IMP depletion results in increased stimulus-dependent MEK
      activation without alterations in the timing or duration of the response. These
      observations suggest that IMP functions as a threshold modulator, controlling
      sensitivity of the cascade to stimulus and providing a mechanism to allow
      adaptive behaviour of the cascade in chronic or complex signalling environments.

PMID- 14724644
TI  - Starting the brain gain.

PMID- 14724645
TI  - Destressing in the geekosphere.

PMID- 14724646
TI  - Graduate journal: at the crossroads.

PMID- 14724647
TI  - Bricks & mortar: Lancaster Environment Centre.

PMID- 14724649
TI  - Glucocorticoid receptor alpha, beta and gamma expression vs in vitro
      glucocorticod resistance in childhood leukemia.
AB  - Alternative splicing of the primary glucocorticoid receptor (GR) transcript,
      resulting in glucocorticoid receptor alpha GRalpha, glucocorticoid receptor beta
      GRbeta and glucocorticoid receptor gamma GRgamma, may influence glucocorticoid
      (GC) resistance in childhood leukemia. To test this hypothesis, we determined
      GRalpha/beta protein and GRalpha/beta/gamma mRNA expression levels in 43 initial
      acute lymphoblastic leukemia (iALL), 10 initial myeloid leukemia (iAML), 11
      relapsed ALL (rALL) samples and one rAML sample. The results were correlated with
      in vitro GC resistance. GRalpha mRNA correlated with protein expression (rho=0.39
      0.56, P<0.05), but the protein to mRNA ratio was median 2.2-fold lower in rALL
      than in iALL (P<0.05). GRbeta mRNA was median 137-fold lower than GRalpha mRNA
      and correlated with GRalpha mRNA expression (rho=0.71, P<0.0001). GRbeta could
      not be detected at the protein level. GRgamma accounted for a median of 2.8%
      (range 0.95-7.4%) of all GR transcripts. GRalpha (protein and mRNA) and GRbeta
      (mRNA) expressions or GRalpha/GRbeta ratios did not correlate with in vitro GC
      resistance in iALL, but GRgamma (mRNA) did (rho=0.52, P=0.007). These results
      suggest that GRbeta is not involved in GC resistance in childhood leukemia. The
      association between GRgamma expression and in vitro GC resistance in iALL and the
      decreased protein/mRNA ratio in rALL, a subgroup resistant to GCs, warrants
      further exploration.

PMID- 14724650
TI  - Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell
      differentiation.
AB  - Lack of apoptosis has been linked to prolonged survival of malignant B cells
      expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2
      protein expressed along normal human B-cell maturation and to establish the
      frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone
      marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow
      cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell
      precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2
      expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and
      lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to
      CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with
      normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144
      patients was found to be aberrant in 66% of the cases, usually corresponding to
      bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT
      lymphoma were the only diagnostic groups constantly showing overexpression of bcl
      2. Bcl-2 overexpression was also frequently found in precursor B-acute
      lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic
      lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell
      lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma,
      Burkitt lymphoma and multiple myeloma.

PMID- 14724651
TI  - Interstitial pneumonia induced by imatinib mesylate: pathologic study
      demonstrates alveolar destruction and fibrosis with eosinophilic infiltration.

PMID- 14724652
TI  - P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic
      myelogenous leukemia cells to treatment with imatinib mesylate.
AB  - Imatinib (Glivec), STI571) is an intracellular acting drug that demonstrates high
      activity against BCR-ABL-positive chronic myelogenous leukemia (CML) or acute
      lymphoblastic leukemia (ALL). However, many patients, especially with advanced
      disease, develop drug resistance. Here, we show by a novel high-performance
      liquid chromatography-based method that intracellular levels of imatinib decrease
      in P-glycoprotein (Pgp)-positive leukemic cells. In a model of K562 cells with
      gradually increasing Pgp expression, a Pgp-dependent decline of intracellular
      imatinib levels was observed. Decreased imatinib levels were associated with a
      retained phosphorylation pattern of the Bcr-Abl target Crkl and loss of effect of
      imatinib on cellular proliferation and apoptosis. The modulation of Pgp by
      cyclosporin A (CSA) readily restored imatinib cytotoxicity in these cells.
      Finally, we provide first data showing a biological effect of Pgp modulation in
      the imatinib treatment of a patient with BCR-ABL-positive ALL. MDR1
      overexpression must therefore be considered as an important clinical mechanism in
      the diversity of resistance development to imatinib treatment.

PMID- 14724653
TI  - Upregulation of asparagine synthetase fails to avert cell cycle arrest induced by
      L-asparaginase in TEL/AML1-positive leukaemic cells.
AB  - L-Asparaginase is a standard component in chemotherapy of childhood acute
      lymphoblastic leukaemia (ALL). Leukaemic cells carrying TEL/AML1 fusion gene are
      more sensitive to treatment with L-asparaginase compared to other subtypes of
      ALL. We demonstrate in vitro the prolonged growth suppression of TEL/AML1[+]
      cells compared to TEL/AML1[-] leukaemic cells after L-asparaginase treatment
      simulating treatment protocol. Cell cycle analysis revealed TEL/AML1[+] cells to
      accumulate in G1/G0 phase (81-98%) compared to TEL/AML1[-] cells (47-60%).
      Quantitative analysis of asparagine synthetase (AsnS) expression showed the
      ability of TEL/AML1[+] cells to increase AsnS mRNA levels after L-asparaginase
      treatment to the same extent as TEL/AML1[-] leukaemic and nonleukaemic lymphoid
      cells. We hypothesise that TEL/AML1[+] cells are unable to progress into the S
      phase of cell cycle under nutrition stress caused by L-asparaginase, despite the
      ability of AsnS upregulation. Significantly higher expression of AsnS was found
      in untreated leukaemic cells from children with TEL/AML1[+] ALL (n=20) in
      comparison with the group of age-matched children with ALL bearing no known
      fusion gene (n=25; P=0.0043). Interestingly, none of the TEL/AML1[+] patients
      with high AsnS level relapsed, whereas 10/15 patients with AsnS below median
      relapsed (P=0.00028). Therefore, high AsnS levels in TEL/AML1[+] patients
      correlate with better prognosis, possibly reflecting the stretched metabolic
      demand of the lymphoblast.

PMID- 14724654
TI  - Caloric restriction and body weight independently affect longevity in Wistar
      rats.
AB  - OBJECTIVE: To evaluate the independent effects of caloric restriction (CR) and
      body weight (BW) on mortality rate (MR) and the extent to which BW may mediate
      the effect of CR on MR. DESIGN AND SUBJECTS: Data were from the Biosure Study, a
      randomized, controlled, prospective intervention study of diet regimens in 1200
      Wistar rats. Animals were followed until they died spontaneously, were euthanized
      because of illness, or reached age 30 months. STATISTICAL ANALYSIS: Cox
      regression was performed to evaluate the effects of CR and BW on MR. Bootstrap
      procedures were used to test the contribution of BW to the effect of CR on MR.
      RESULTS: CR initiated after age 13 weeks decreased the rate of subsequent
      mortality. The MR increased with higher BW in early adulthood (21 weeks) and this
      effect persisted even after adjustment for CR. After adjustment for BW in early
      adulthood, we did not find a similar relation between mortality and BW in late
      adulthood (105 weeks). Mediation analysis indicated that low BW associated with
      CR appeared to mediate some of the mortality-reducing effects of CR, but CR
      clearly had effects independent of BW. The reductions in BW appeared to account
      for approximately 11% of the effect of CR. CONCLUSION: CR and BW have independent
      effects on MR in Wistar rats. BW may mediate a small part of the CR effects on
      MR.

PMID- 14724655
TI  - Type II diabetes mellitus and impaired glucose regulation in Caucasian children
      and adolescents with obesity living in Germany.
AB  - BACKGROUND: Recent studies reported an increased prevalence of type II diabetes
      mellitus in obese children and adolescents, especially in specific ethnic
      subgroups. The aim of this study was to determine the prevalence of type II
      diabetes mellitus and impaired glucose regulation in a large group of Caucasian
      children and adolescents with obesity living in Germany. PATIENTS AND METHODS: A
      total of 520 subjects (237 boys, 283 girls) (mean age: 14.0+/-2.0 y (range 8.9
      20.4 y)) with a BMI>97th percentile, BMI-SDS: 2.7+/-0.5 (range 1.9-4.6), who were
      consecutively admitted to an in-patient obesity unit participated in the study. A
      2-h oral glucose tolerance test (1.75 mg of glucose per kilogram of body weight)
      was performed before entering a weight-loss program and capillary blood glucose
      concentrations were measured. Patients were categorized into normal glucose
      regulation, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and
      diabetes. In addition, fasting venous blood was taken to determine the
      circulating insulin, C-peptide and lipids. Insulin resistance was estimated by
      homeostatic model assessment. RESULTS: Type II diabetes was present in 1.5% (n=8)
      of the patients, two patients were admitted with already diagnosed type II
      diabetes and six patients were identified with yet unknown diabetes. IFG was
      detected in 3.7% (n=19) and IGT in 2.1% (n=11) of the patients. All together, in
      6.7% (n=35) (95% confidence interval: 4.7-9.2%) of the patients, impaired glucose
      regulation (IFG, IGT) or diabetes was identified. These patients had a higher BMI
      SDS, higher levels of fasting insulin and C-peptide and a higher insulin
      resistance index than the patients with normal glucose regulation. Risk factors
      for the occurrence of impaired glucose regulation were a BMI-SDS>2.5 as well as a
      positive parents' history for diabetes. CONCLUSIONS: This is the first report on
      the prevalence of type II diabetes in a large cohort of Caucasian children and
      adolescents with obesity living in Europe. Impaired glucose regulation and type
      II diabetes were present in a substantial proportion of the patients studied.
      Screening for diabetes in severely obese children and adolescents (BMI-SDS>2.5)
      is therefore recommended. Patients identified with impaired glucose regulation
      need specific treatment programs in order to prevent progression to diabetes.

PMID- 14724656
TI  - Genetic variation in the corticotrophin-releasing factor receptors:
      identification of single-nucleotide polymorphisms and association studies with
      obesity in UK Caucasians.
AB  - OBJECTIVE: To investigate whether genetic variation at the loci encoding the
      corticotropin-releasing factor receptors-1 and -2 (CRF-R1 and CRF-R2) contributes
      to human obesity. DESIGN: The coding region of the CRF-R1 and CRF-R2 genes was
      screened in 51 severely obese children (body mass index (BMI)>4 kg/m(2) standard
      deviations above the age-related mean) using denaturing high-performance liquid
      chromatography and direct nucleotide sequencing. Common polymorphisms that were
      identified were typed from a UK Caucasian population-based cohort by a PCR-based
      forced restriction digestion. A repeated measures analysis was used to determine
      associations between the C861T and G1047A genotypes and anthropometric and
      biochemical indices relevant to obesity. RESULTS: In subjects with extreme early
      onset obesity, four missense mutations were found, each in a single individual:
      CRF-R1 (Val161Met) and CRF-R2 (Glu220Asp, Val240Ile and Val411Met). However, none
      of these missense mutations clearly cosegregated with obesity in family studies.
      Two common single-nucleotide polymorphisms, C861T (Cys287Cys) in CRF-R1 and
      G1047A (Ser349Ser) in CRF-R2, were also detected. G1047A did not associate with
      any obesity-related phenotype. In contrast, carriers of the CRF-R1 polymorphism,
      C861T, had a significantly higher body mass index (BMI). CONCLUSION: Mutations in
      the coding sequence of the CRF-R1 and CRF-R2 genes are unlikely to be a common
      monogenic cause of early-onset obesity. In an adult UK Caucasian population, the
      CRF-R1 C861T polymorphism is associated with increased BMI.

PMID- 14724657
TI  - Muscle insulin receptor concentrations in obese patients post bariatric surgery:
      relationship to hyperinsulinemia.
AB  - OBJECTIVE: Obesity results in insulin resistance. Bariatric surgery for obese
      individuals induces weight loss, improves insulin sensitivity, and lowers insulin
      levels. We investigated the mechanisms of this improvement. DESIGN: Insulin
      receptor (IR) content, IR signaling, and adiponectin levels were measured in nine
      morbidly obese subjects before and after bariatric surgery. SUBJECTS: Seven
      female and two male, average age 44+/-2y, BMI >40 kg/m(2) and/or at least 100 lbs
      over ideal body weight, undergoing elective bariatric surgery. MEASUREMENTS:
      Before surgery BMI, fasting plasma glucose, adiponectin, and insulin levels were
      measured. A fasting muscle biopsy was obtained from the vastus lateralis for IR
      concentration and autophosphorylation activity measurements. These procedures
      were repeated 1 y after surgery. RESULTS: At 1 y after surgery, the subjects had
      lost an average of 48.3+/-5.6 kg (P<0.001), insulin sensitivity had significantly
      increased as determined by the minimal model (SI 0.72+/-0.18 vs 3.86+/-1.43,
      P<0.05), and IR content had increased two-fold in muscle (2.1+/-0.4 vs 4.3+/-0.7
      ng/mg protein, P<0.01). The increase in IR content was related to fasting insulin
      levels. In the subjects with the lowest IR function, there was also an increase
      in IR function. Plasma adiponectin increased by 40% following weight loss (7.4+/
      1.6 pre vs 10.3+/-1.3 mg/ml post, P<0.05). There was no significant change in
      muscle content of the IR inhibitor, PC-1. CONCLUSION: Increased IR content, most
      likely regulated by insulin levels, may be one contributor to the increased
      insulin sensitivity that occurs when morbidly obese patients undergo bariatric
      surgery.

PMID- 14724658
TI  - Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and
      omental adipose tissue.
AB  - OBJECTIVE: In the current study, we addressed the question if there is depot
      specific expression of cellular inhibitor of apoptosis protein-2 (cIAP2) already
      in childhood and if the relative expression changes with age in parallel with
      increasing risk of developing visceral adiposity. SUBJECTS: Paired samples of
      human omental (OM) and subcutaneous (SC) adipose tissue were obtained from 23
      patients (12 children and 11 adults). METHOD: mRNA level of cIAP2 was determined
      using reverse transcription-polymerase chain reaction (RT-PCR) and protein
      expression confirmed by Western blotting. Apoptosis indices were determined by
      terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end
      labelling (TUNEL). RESULTS: cIAP2 mRNA was 1.51-fold higher in OM compared with
      SC adipose tissue (OM>SC in 20 of 23 subjects; P<0.001). Western blots were in
      agreement with mRNA expression (OM>SC in nine of 10 subjects, P<0.01). Subgroup
      analyses showed depot difference in both children (P<0.01) and adults (P<0.05).
      Contrary to the hypothesis, depot-specific difference in mRNA expression of cIAP2
      was significantly higher in children compared with adults (P<0.05). We were
      unable to demonstrate any difference in the basal apoptosis rate between
      adipocytes from the two depots. There was no significant association between
      cIAP2 mRNA expression and BMI or sex. CONCLUSIONS: The results demonstrated for
      the first time that depot-specific difference in cIAP2 expression is consistent
      in children and adults. This suggests that the higher expression of cIAP2 in OM
      than in SC adipose tissue may be due to inherent properties of cells from the two
      depots. The more pronounced depot-specific difference in children than in adults
      may reflect a net gain in visceral adipose tissue during growth.

PMID- 14724659
TI  - Independent and opposite associations of waist and hip circumferences with
      diabetes, hypertension and dyslipidemia: the AusDiab Study.
AB  - OBJECTIVE: Fat distribution as measured by waist-to-hip ratio has been shown to
      be an important independent predictor of glucose intolerance. Few studies,
      however, have considered the contributions of the waist and hip circumferences
      independently. The aim of this study was to investigate the independent
      associations of waist and hip circumference with diabetes in a large population
      based study, and to investigate whether they also apply to other major components
      of the metabolic syndrome (hypertension and dyslipidemia). In addition, as
      previous studies were performed in older persons, we investigated whether these
      associations were present across adult age groups. METHODS: Weight, height, waist
      and hip circumferences were measured in 11 247 participants of the nationally
      representative Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. HDL
      cholesterol, triglycerides, fasting and 2-h postload glucose were determined, and
      diastolic and systolic blood pressure was measured. After exclusion of persons
      already known to have diabetes, hypertension or dyslipidemia, logistic and linear
      regression were used to study cross-sectional associations of anthropometric
      variables with newly diagnosed diabetes, hypertension and dyslipidemia, and with
      continuous metabolic measures, all separately for men (n=3818) and women
      (n=4582). Analyses were repeated in the same population stratified for age.
      RESULTS: After adjustment for age, body mass index and waist, a larger hip
      circumference was associated with a lower prevalence of undiagnosed diabetes
      (odds ratio (OR) per one s.d. increase in hip circumference 0.55 (95% CI 0.41
      0.73) in men and 0.42 (0.27-0.65) in women) and undiagnosed dyslipidemia (OR 0.58
      (0.50-0.67) in men and 0.37 (0.30-0.45) in women). Associations with undiagnosed
      hypertension were weaker (OR 0.80 (0.69-0.93) in men and 0.88 (0.70-1.11) in
      women). As expected, larger waist circumference was associated with higher
      prevalence of these conditions. Similar associations were found using continuous
      metabolic variables as outcomes in linear regression analyses. Height partly
      explained the negative associations with hip circumference. When these analyses
      were performed stratified for age, associations became weaker or disappeared in
      the oldest age groups (age > or =75 y in particular), except for HDL-cholesterol.
      CONCLUSION: We found independent and opposite associations of waist and hip
      circumference with diabetes, dyslipidemia and less strongly with hypertension in
      a large population-based survey. These results emphasize that waist and hip
      circumference are important predictors for the metabolic syndrome and should both
      be considered in epidemiological studies. The associations were consistent in all
      age groups, except in age > or =75 y. Further research should be aimed at
      verifying hypotheses explaining the 'protective' effect of larger hips.

PMID- 14724660
TI  - Effect of long-term body weight change on the incidence of hypertension in
      Japanese men and women.
AB  - OBJECTIVE: To elucidate the effect of long-term body weight changes on the
      subsequent incidence of hypertension in a large sample of community-residing
      Japanese males and females. METHODS: Subjects were 3431 men and 2409 women,
      between 30 and 69 y old, who underwent annual periodic health examinations from
      1987 (baseline year) until 1996. They were free from hypertension during the
      first 5 y from the baseline year. Body weight change index between 1987 and 1992
      was the body mass index (BMI) (weight (kg) over height (m) squared) slope.
      Multiple logistic analysis was performed to assess the effect of BMI slope on the
      incidence of hypertension during the subsequent 5 ys (1992-1996), while
      controlling for baseline age, BMI, systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and smoking habit. RESULTS: During the first 5 y, the prevalence
      of overweight males (25.0< or =BMI<30.0) significantly increased from 18.4 to
      23.5% in males and from 10.4 to 14.1% in females. In all, 11.7% of the males and
      8.9% of the females developed hypertension between 1992 and 1996. Those who
      developed hypertension had a significantly higher baseline age, BMI, SBP and DBP
      both in males and females. The baseline smoking rate among the females who
      developed hypertension was significantly lower than those who did not develop the
      hypertension. After adjustment of these covariables by the multiple logistic
      analysis, the BMI slope was positively correlated with the incidence of
      hypertension both in females and males significantly. CONCLUSIONS: Weight gain
      increased the risk of developing hypertension independent of age and blood
      pressure level among relatively lean Japanese men and women.

PMID- 14724661
TI  - BMI change and leisure time physical activity (LTPA): an 11-y follow-up study in
      apparently healthy men aged 20-69 y with normal weight at baseline.
AB  - OBJECTIVE: To study the association between self-reported leisure time physical
      activity (LTPA) at baseline and change in body mass index (BMI). DESIGN:
      Prospective observational study with a 11-y follow-up period. SETTING: A total
      population-based health survey in one county was performed in 1984-1986 (HUNT 1)
      and repeated in 1995-1997 (HUNT 2). PARTICIPANTS: In total, 21 685 men
      participated in both surveys. In the present study, we included only apparently
      healthy 20-69-y-old men participating in both surveys and who had a normal body
      weight (BMI 18.5-24.9 kg/m(2)) at baseline-leaving 8305 men for the analyses. In
      all, 6945 men answered all questions about LTPA and 6749 men had complete data in
      the multiple analyses. MEASUREMENTS AND MAIN RESULTS: At HUNT 1, the participants
      answered questions (self-reported) about the intensity, frequency and duration of
      LTPA. The association between change in BMI and LTPA was investigated in multiple
      linear regression analyses. Adjusted for smoking, education, age and BMI at
      baseline, the physical active cohort gained less weight than the inactive cohort.
      Low, moderate and high levels of LTPA showed a U-shaped effect adjusted for
      smoking, education, age and BMI at baseline. Adjusted for BMI and age at
      baseline, the high-intensity part of the physically active cohort gained less
      weight than the low-intensity group. CONCLUSION: This study has demonstrated a
      moderate BMI effect of LTPA at the population level; however, even a high level
      of LTPA did not prevent weight gain during the 11-y follow-up period.

PMID- 14724662
TI  - Binge eating disorder, weight control self-efficacy, and depression in overweight
      men and women.
AB  - OBJECTIVE: To examine binge eating, depression, weight self-efficacy, and weight
      control success among obese individuals seeking treatment in a managed care
      organization. DESIGN: Gender-stratified analyses of associations between binge
      eating, depression, weight self-efficacy, and weight change, using data from a
      randomized clinical trial that compared low-cost telephone-based, mail-based, and
      usual care interventions for weight loss. SUBJECTS: A total of 1632 overweight
      individuals (460 men, 1172 women; mean age: 50.7 y; mean body mass index: 34.2
      kg/m(2)) were recruited from a large Midwestern US managed care organization.
      MEASUREMENTS: Height and weight were measured by study personnel at baseline, and
      self-reported weight was assessed at 6 and 12 months; self-reported depression
      status, binge eating, and self-efficacy for weight control were assessed at
      baseline. RESULTS: Lifetime prevalence rates for depression and probable binge
      eating disorder were high. Weight self-efficacy was inversely related to weight
      in both men and women. For women, depression was associated with lower weight
      self-efficacy and higher body weight. Women reporting depression or lower weight
      self-efficacy at baseline had less weight loss success at 6 and 12 months.
      Depression, binge eating disorder, and weight self-efficacy were not
      significantly associated with weight loss success in men. CONCLUSION: Negative
      emotional states are highly prevalent and predict poor treatment outcomes,
      particularly for obese women. As obese women with clinical depression typically
      are excluded from intervention studies, further research on how to address the
      intersection of obesity intervention and mood management may be warranted.

PMID- 14724663
TI  - Body morphology differentially predicts coronary calcium.
AB  - OBJECTIVE: To test the hypothesis that three measures of body morphology would be
      differentially correlated with and predictive of coronary artery calcification.
      DESIGN: Cross-sectional analytic study of body mass index (BMI), central
      adiposity ('visceral fat') and total body percent fat. SUBJECTS: In a total of
      3028 healthy, free living men and women (mean age and BMI: 56.7 and 27.0,
      respectively). MEASUREMENTS: Coronary calcification and visceral fat (VF) content
      was measured using electron beam computed tomography while percent body fat (BF)
      was determined using bioimpedence. RESULTS: In men, the median coronary calcium
      score increased from 6.7 for a BMI < or =24 to 30.9 for a BMI > or =30; from 3.6
      to 46.4 between the first and fourth quartile of VF; and from 1 to 97.6 for the
      same in BF. There were no significant increases in calcium scores in women for
      any of these indices. There were also no significant age-adjusted correlations
      between BMI, BF and VF with the extent of coronary calcium in either gender. On
      multivariable logistic regression analysis, men with a BMI in the third and
      fourth quartiles had 1.64 and 2.01 times increase in risk, respectively, for the
      presence of any coronary calcium compared to those in the first quartile (P< or
      =0.01 for both) while men in the highest quartile for VF had a 63% increase in
      this same risk (P=0.04). For women, a BMI in the fourth quartile was associated
      with a 68% increase in risk for the presence of any coronary calcium (P=0.01).
      CONCLUSION: BMI is a significant predictor of coronary calcium. In men, central
      adiposity is also an independent predictor. These findings lend further support
      to weight control for coronary disease prevention.

PMID- 14724664
TI  - Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met
      variant is associated with an earlier onset of obesity.
AB  - OBJECTIVE: To test whether ghrelin variants could play a role in modulating some
      aspects of the obese phenotype during childhood. DESIGN: We screened the ghrelin
      gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range
      4-19 y) and 200 controls by using the single-strand conformation polymorphism and
      the restriction fragment length polymoprhism analysis. RESULTS: No mutations were
      detected with the exception of two previously described polymorphisms, Arg51Gln
      and Leu72Met. For both variations, allelic frequencies were similar between
      patients and controls. Interestingly, we showed that the Leu72Met polymorphism
      was associated with differences in the age at obesity onset. Patients with the
      Met72 allele became obese earlier than homozygous patients for the wild Leu72
      allele. The logrank test comparing the plots of the complement of Kaplan-Meier
      estimates between the two groups of patients was statistically significant
      (P<0.0001). CONCLUSION: It is unlikely that ghrelin variations cause the obesity
      due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems
      to play a role in anticipating the onset of obesity among children suggesting,
      therefore, that ghrelin may be involved in the pathophysiology of human
      adiposity.

PMID- 14724665
TI  - Effect of low-dose metoprolol in combination with sibutramine therapy in
      normotensive obese patients: a randomized controlled study.
AB  - OBJECTIVE: Sibutramine is an effective appetite suppresser agent, but treatment
      is often complicated with side effects, including palpitations and hypertension.
      In this study, we aimed to assess the effect of low-dose cardio-selective beta
      blocker combination with sibutramine treatment. METHODS: In total, 57 obese
      subjects were enrolled in the study and separated into two groups in order to
      receive sibutramine 10 mg/day plus placebo (group P) or sibutramine 10 mg/day
      plus metoprolol 25 mg/day (group M). Patients were evaluated in the beginning and
      at the end of the third month with anthropometric measurements, biochemical
      analysis, peripheral insulin resistance, and ambulatory 24 h blood pressure
      monitoring. Side effects were evaluated with a visual analog scale. RESULTS:
      During the study period, the drop-out rate was significantly higher in group P
      compared with group M (55 and 21%, respectively, P=0.014). Palpitations and
      headache were prominent symptoms in group P. Diastolic blood pressure (78.6+/
      11.6 and 70.6+/-4.8 mmHg, respectively, P=0.013) and mean heart rate (84.3+/-6.1
      and 75.8+/-8.4 beats/min, respectively, P=0.003) were significantly higher in
      group P compared with group M at the end of the third month. Weight loss was
      similar between the two groups (100.9+/-11.5 to 91.8+/-12.8 kg for group P,
      P<0.0001 and 97.9+/-13.2 to 88.9+/-13.8 kg for group M, P<0.0001). We did not
      find any deleterious effect of metoprolol on metabolic parameters. CONCLUSION:
      Addition of low-dose metoprolol to sibutramine therapy increased patient
      compliance to the treatment, and decreased the frequency and severity of side
      effects including hypertension and palpitations, without decreasing the drug
      efficacy or causing significant deleterious changes in metabolic parameters.

PMID- 14724666
TI  - Uncoupling proteins: gender-dependence and their relation to body weight control.
AB  - The members of the uncoupling protein family have different purported functions,
      which can be either directly or indirectly related to the control of body weight.
      In this sense, a great part of the studies carried out on this topic have been
      made using male subjects, although different works with male and female subjects
      have shown important sex-associated differences in the regulation of these
      proteins; for instance, sex differences have been shown in the cold-, diet- and
      overweight-induced expression of brown adipose tissue UCP1 and also in the
      correlation of muscle UCP3 with overweight. In these kinds of studies, models of
      obesity such as the cafeteria diet feeding and postcafeteria have been very
      useful. Moreover, sex hormones have been shown to modulate UCP1 expression in
      brown adipocytes in vitro. All of these sex-dependent differences, as well as sex
      differences in body weight gain under a hypercaloric diet, could be related to
      the different respective biological functions of male and female subjects and
      taking into account the gender effect in future studies on obesity could be of
      interest.

PMID- 14724667
TI  - Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP
      promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's
      disease.
AB  - A new adenoviral vector (Ad-GFAP-GDNF) (Ad=adenovirus, GFAP=glial fibrillary
      acidic protein, GDNF=glial cell line-derived neurotrophic factor) was constructed
      in which (i) the E1,E3/E4 regions of Ad5 were deleted and (ii) the GDNF transgene
      is driven by the GFAP promoter. We verified, in vitro, that the recombinant GDNF
      was expressed in primary cultures of astrocytes. In vivo, the Ad-GFAP-GDNF was
      injected into the striatum of rats 1 week before provoking striatal 6-OHDA
      lesion. After 1 month, the striatal GDNF levels were 37 pg/microg total protein.
      This quantity was at least 120-fold higher than in nontransduced striatum or
      after injection of the empty adenoviral vector. At 3 months after viral
      injection, GDNF expression decreased, whereas the viral DNA remained unchanged.
      Furthermore, around 70% of the dopaminergic (DA) neurons were protected from
      degeneration up to 3 months as compared to about 45% in the control groups. In
      addition, the amphetamine-induced rotational behavior was decreased. The results
      obtained in this study on DA neuron protection and rotational behavior are
      similar to those previously reported using vectors with viral promoters. In
      addition to these results, we established that a high level of GDNF was present
      in the striatum and that the period of GDNF expression was prolonged after
      injection of our adenoviral vector.

PMID- 14724668
TI  - Uptake and trafficking of DNA in keratinocytes: evidence for DNA-binding
      proteins.
AB  - The skin is an interesting organ for human gene therapy due to accessibility,
      immunologic potential and synthesis capabilities. In this study, we attempted to
      visualize and measure the uptake of naked FITC-labeled plasmid by FACS analysis
      detecting up to 15% internalization in a dose- and time-dependent manner.
      Cycloheximide treatment inhibited the uptake by >90%, suggesting a protein
      mediated uptake. The inhibition of different internalization pathways
      demonstrated that blocking macropinocytosis (by amiloride and N,N
      dimethylamylorid) reduced DNA uptake by >85%, while the inhibition of clathrin
      coated pits (by chlorpromazine) and caveolae (by nystatin/filipin III) did not
      limit the uptake. Colocalization studies using confocal laser microscopy revealed
      a time-dependent accumulation of plasmid DNA in endosomes and lysosomes. When a
      green fluorescent protein (GFP) expression vector was used, specific GFP-RNA
      became detectable by reverse transcriptase-PCR, whereas measurable amounts of
      protein could not be identified in FACS experiments. To detect the potential DNA
      receptors on the keratinocyte surface, membrane proteins were extracted and
      subjected to South-Western blotting using digoxigenin-labeled calf thymus and
      lambda-phage DNA. Two DNA-binding proteins, ezrin and moesin, known as plasma
      membrane-actin linkers, were identified by one- and two-dimensional-South-Western
      blots and matrix-assisted laser desorption and ionization-mass spectrometry.
      Ezrin and moesin are functionally associated with a number of transmembrane
      receptors such as the EGF, CD44 or ICAM-1 receptor. Taken together, naked plasmid
      DNA seems to enter human keratinocytes through different pathways, mainly by
      macropinocytosis. Two DNA-binding proteins were identified that seemed to be
      involved in binding/trafficking of internalized DNA.

PMID- 14724669
TI  - Genetically engineered Sertoli cells are able to survive allogeneic
      transplantation.
AB  - The immunoprotective nature of the testis has led to numerous investigations for
      its ability to protect cellular grafts. Sertoli cells (SCs) are at least
      partially responsible for this immunoprotective environment and survive
      allogeneic and xenogeneic transplantation. The ability of SCs to survive
      transplantation leads to the possibility that they could be engineered to deliver
      therapeutic proteins. As a model to test this hypothesis, we examined the ability
      of SCs that produce green fluorescent protein (GFP) to survive transplantation
      and continue expressing GFP. SCs were isolated from transgenic mice engineered to
      express GFP and transplanted as aggregates under the kidney capsule of severe
      combined immunodeficient (SCID) and Balb/c mice. Using this paradigm, it was
      possible to compare the survival of transgenic SCs directly in both
      immunodeficient and immunocompetent recipients. Fluorescence microscopy of the
      kidney capsule and immunohistochemistry of the grafts for GFP and GATA-4 revealed
      the presence of GFP-expressing SCs under the kidney capsule of SCID and Balb/c
      mice at both 30 and 60 days post-transplantation. In contrast, islets
      transplanted to Balb/c mice were rejected. Thus, SCs survive transplantation and
      continue to express GFP raising the possibility that SCs can be engineered using
      transgenic technology to produce proteins, such as insulin, factor VIII, or
      dopamine for the treatment of diabetes, hemophilia or Parkinson's disease,
      respectively.

PMID- 14724670
TI  - Foamy virus--adenovirus hybrid vectors.
AB  - To confer adenovirus vectors (AdV), the feature of integration into the host cell
      genome hybrid vectors were characterized in vitro, which express vectors derived
      from the prototypic foamy virus (FV) in the backbone of a high-capacity AdV. FVs
      constitute a subfamily of retroviruses with a distinct replication pathway and no
      known pathogenicity. In the absence of envelope glycoprotein, the prototypic FV
      behaves like a retrotransposon, while it behaves like an exogenous retrovirus in
      its presence. Two principle types of vectors, which either allows the
      intracellular (HC-FAD-7) or, in addition, the extracellular (HC-FAD-2) pathway
      were constructed. In both chimeras the expression of the FV vector was controlled
      by the tetracycline-regulatable system. Hybrids were produced close to 10(10)
      infectious units/ml. By Southern blotting, the functionality of the hybrid
      vectors to generate host cell genomic integrants was shown. However, the
      efficiency of HC-FAD-7 to establish stable transgene expression was rather low,
      while around 70% of cells were stably transduced in secondary round following
      primary transduction with HC-FAD-2 at an MOI of 100. Given the benign
      characteristics of high-capacity adenovirus and FV vectors, hybrids based on HC
      FAD-2 are probably suited for an in vivo application.

PMID- 14724671
TI  - Cationic corticosteroid for nonviral gene delivery.
AB  - Delivery of plasmid DNA for gene therapy often provokes an inflammatory response
      that reduces transgene expression. Cationic lipids for lipofection lack
      pharmacological activity despite the hydrophobicity of many drug candidates that
      could be exploited. We report a one-step synthesis of a water-soluble,
      dexamethasone-spermine (DS) cationic lipid that has potent gene transfer
      capability in confluent endothelial cells when used with the neutral lipid,
      dioleoylphosphatidylethanolamine (DOPE). In contrast, unconjugated mixtures of
      dexamethasone, spermine, and/or DOPE have essentially no gene transfer activity.
      DS retains partial corticosteroid character as quantified by the rapid
      translocation of glucocorticoid receptor to the nucleus and by dose-dependent
      transactivation from a glucocorticoid response element. DS has anti-inflammatory
      activity in vivo in the mouse thioglycollate model of inflammation. In a mouse
      lung model, DS:DOPE resulted in significantly less interferon-gamma production at
      Day 1 and elevated transgene expression at Days 1 and 7 postintranasal
      instillation compared to DC-Chol:DOPE (sterol:DOPE:phosphate molar ratio of
      1:1:1). Cationic pharmacophores such as DS represent a new approach to gene
      delivery and localized therapy.

PMID- 14724672
TI  - Detection of integration of plasmid DNA into host genomic DNA following
      intramuscular injection and electroporation.
AB  - Plasmid vectors have been widely used for DNA vaccines and gene therapy.
      Following intramuscular injection, the plasmid that persists is extrachromosomal
      and integration into host DNA, if it occurs at all, is negligible. However, new
      technologies for improving DNA delivery could increase the frequency of
      integration. In the present study, we tested the effect of electroporation on
      plasmid uptake and potential integration following intramuscular injection in
      mice, using a plasmid containing the mouse erythropoietin gene. Electroporation
      increased plasmid tissue levels by approximately six- to 34-fold. Using a
      quantitative gel-purification assay for integration, electroporation was found to
      markedly increase the level of plasmid associated with high-molecular-weight
      genomic DNA. To confirm integration and identify the insertion sites, we
      developed a new assay - referred to as repeat-anchored integration capture (RAIC)
      PCR - that is capable of detecting rare integration events in a complex mixture
      in vivo. Using this assay, we identified four independent integration events.
      Sequencing of the insertion sites suggested a random integration process, but
      with short segments of homology between the vector breakpoint and the insertion
      site in three of the four cases. This is the first definitive demonstration of
      integration of plasmid DNA into genomic DNA following injection in vivo.

PMID- 14724673
TI  - Hydroporation as the mechanism of hydrodynamic delivery.
AB  - We have reported that a rapid tail vein injection of a large volume of plasmid
      DNA solution into a mouse results in high level of transgene expression in the
      liver. Gene transfer efficiency of this hydrodynamics-based procedure is
      determined by the combined effect of a large volume and high injection speed.
      Here, we show that the hydrodynamic injection induces a transient irregularity of
      heart function, a sharp increase in venous pressure, an enlargement of liver
      fenestrae, and enhancement of membrane permeability of the hepatocytes. At the
      cellular level, our results suggest that hepatic delivery by the hydrodynamic
      injection is accomplished by the generation of membrane pores in the hepatocytes.

PMID- 14724674
TI  - Efficient bone formation by gene transfer of human LIM mineralization protein-3.
AB  - LIM mineralization protein (LMP) is a novel positive regulator of the osteoblast
      differentiation program. In humans, three different LMP splice variants have been
      identified: LMP-1, LMP-2, and LMP-3. Gene transfer of human LMP-1 (hLMP-1)
      induces expression of genes involved in bone formation, including certain bone
      morphogenetic proteins (BMPs), promotes bone nodule formation in vitro, ectopic
      bone formation in vivo, and is therapeutic in animal models of posterior thoracic
      and lumbar spine fusion. To examine the osteoinductive properties of the LMP-3 in
      vitro and in vivo, we have generated plasmid and adenoviral vectors expressing
      codon-optimized hLMP-3. Here we demonstrate that gene transfer of hLMP-3 induces
      expression of the bone-specific genes osteocalcin, osteopontin, and bone
      sialoprotein and induced bone mineralization in preosteoblastic and fibroblastic
      cells. We also demonstrate that hLMP-3 is able to induce bone mineralization and
      the expression of the bone-specific genes, BMP-2, OSX, RunX2, and alkaline
      phosphatase in human mesenchymal stem cells in a dose-dependent manner. Finally,
      we demonstrate that direct gene transfer of hLMP-3 into murine skeletal muscle
      results in ectopic bone formation more efficiently than BMP-2. These results
      demonstrate that hLMP-3 gene transfer can be used to promote bone formation in
      cell culture and in vivo as or more efficiently than BMP-2, thus establishing
      feasibility and efficacy of direct gene delivery of hLMP-3 to produce bone in
      vivo. These results suggest that gene transfer of hLMP-3 could be developed as a
      bone-inductive therapeutic agent for clinical applications.

PMID- 14724675
TI  - A sensitive noninvasive method for monitoring successful liver-directed gene
      transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic
      rabbits in vivo.
AB  - Noninvasive tools to quantitate transgene expression directly are a prerequisite
      for clinical gene therapy. We established a method to determine location,
      magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR)
      transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe
      hypercholesterolemic rabbits by following tissue uptake of intravenously injected
      (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake
      was calculated by normalizing the counts measured over the liver to counts
      measured over the heart that represent the circulating blood pool of the tracer
      (liver/heart (L/H) ratio). Our results indicate that the optimal time point for
      transgene imaging is 4 h after the tracer injection. Compared with control virus
      injected rabbits, animals treated with the LDLR-expressing adenovirus showed
      seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold
      higher L/H ratios on day 30. This imaging method might be a useful strategy to
      obtain reliable data on functional transgene expression in clinical gene therapy
      trials of familial hypercholesterolemia.

PMID- 14724676
TI  - Reduced toxicity of F-deficient Sendai virus vector in the mouse fetus.
AB  - Current concerns over insertional mutagenesis by retroviral vectors mitigate
      investigations into alternative, potentially persistent gene therapy vector
      systems not dependent on genomic integration, such as Sendai virus vectors
      (SeVV). Prenatal gene therapy requires efficient gene delivery to several
      tissues, which may not be achievable by somatic gene transfer to the adult.
      Initially, to test the potential and tropism of the SeVV for gene delivery to
      fetal tissues, first-generation (replication- and propagation-competent)
      recombinant SeVV, expressing beta-galactosidase was introduced into late
      gestation immunocompetent mice via the amniotic and peritoneal cavities and the
      yolk sac vessels. At 2 days, this resulted in very high levels of expression
      particularly in the airway epithelium, mesothelium and vascular endothelium,
      respectively. However, as expected, substantial vector toxicity was observed. The
      efficiency of gene transfer and the level of gene expression were then examined
      using a second-generation SeVV. The second generation was developed to be still
      capable of cytoplasmic RNA replication and therefore high-level gene expression,
      but incapable of vector spread due to lack of the gene for viral F-protein.
      Vector was introduced into the fetal amniotic and peritoneal cavities,
      intravascularly, intramuscularly and intraspinally; at 2 days, expression was
      observed in the airway epithelia, peritoneal mesothelia, unidentified cells in
      the gut wall, locally at the site of muscle injection and in the dorsal root
      ganglia, respectively. Mortality was dramatically diminished compared with the
      first-generation vector.

PMID- 14724678
TI  - Spine fusion by gene therapy.
AB  - Over 250 000 patients each year undergo a spine fusion procedure in the US. This
      constitutes 50% of all bone graft procedures. Despite best efforts, a large
      percentage of spine fusions (up to 35%) fail to form a solid bony arthrodesis.
      This is a significant clinical problem and has led to research in bone formation
      biology to augment spine fusion rates. Both recombinant and purified
      osteoinductive cytokines have been studied in pilot and pivotal studies in
      humans. At this point, recombinant human bone morphogenetic protein-2 has
      received FDA approved for lumbar interbody application with titanium cages.
      Despite these successes, limitations of directly applying osteoinductive proteins
      related to cost and carriers remain to be overcome. Gene therapy for spine fusion
      and other bone healing applications are being pursued as an alternative strategy.
      This article will review the state of the art of local gene therapy for bone
      formation and to highlight specific issues, which must be addressed when pursuing
      such a program. A critical step in using gene therapy for bone formation is
      choosing an appropriate osteoinductive gene. In choosing the gene, one must
      consider the differences in efficacy of the gene as well as the gene availability
      due to proprietary constraints. The choice of delivery vector is important.
      Factors such as the potency of the gene and the specific application intended
      play a role in this decision. Next, the effective dose, transduction time, and
      gene transfer method must be established. The choice of carrier material to form
      the scaffold for the new bone formation is another critical step that must be
      optimized for successful bone formation. Finally, a strategy for in vitro and in
      vivo testing must be developed to maximize the chances of success in human
      trials.

PMID- 14724679
TI  - Aseptic loosening.
AB  - Although total joint replacement surgery is one of the most successful clinical
      procedures performed today, bone loss around knee and hip implants (osteolysis),
      resulting in aseptic loosening of the prosthesis, remains a major problem for
      many patients. Over the last decade much has been learned about this process,
      which is caused by wear debris particles that simulate a local inflammatory
      response and osteoclastic bone resorption. Aseptic loosening cannot be prevented
      or treated by existing nonsurgical methods. Gene transfer, however, offers novel
      possibilities. Here, we review the current state of the field and the
      experimental gene therapy approaches that have been investigated toward a
      solution to aseptic loosening of prosthetic implants.

PMID- 14724680
TI  - Gene-based approaches for the repair of articular cartilage.
AB  - Gene transfer technology has opened novel treatment avenues toward the treatment
      of damaged musculoskeletal tissues, and may be particularly beneficial to
      articular cartilage. There is no natural repair mechanism to heal damaged or
      diseased cartilage. Existing pharmacologic, surgical and cell based treatments
      may offer temporary relief but are incapable of restoring damaged cartilage to
      its normal phenotype. Gene transfer provides the capability to achieve sustained,
      localized presentation of bioactive proteins or gene products to sites of tissue
      damage. A variety of cDNAs have been cloned which may be used to stimulate
      biological processes that could improve cartilage healing by (1) inducing mitosis
      and the synthesis and deposition of cartilage extracellular matrix components by
      chondrocytes, (2) induction of chondrogenesis by mesenchymal progenitor cells, or
      (3) inhibiting cellular responses to inflammatory stimuli. The challenge is to
      adapt this technology into a useful clinical treatment modality. Using different
      marker genes, the principle of gene delivery to synovium, chondrocytes and
      mesenchymal progenitor cells has been convincingly demonstrated. Following this,
      research efforts have begun to move to functional studies. This involves the
      identification of appropriate gene or gene combinations, incorporation of these
      cDNAs into appropriate vectors and delivery to specific target cells within the
      proper biological context to achieve a meaningful therapeutic response. Methods
      currently being explored range from those as simple as direct delivery of a
      vector to a cartilage defect, to synthesis of cartilaginous implants through gene
      enhanced tissue engineering. Data from recent efficacy studies provide optimism
      that gene delivery can be harnessed to guide biological processes toward both
      accelerated and improved articular cartilage repair.

PMID- 14724681
TI  - Gene therapy for degenerative disc disease.
AB  - Degenerative disc disease (DDD) is a chronic process that can become clinically
      manifest in multiple disorders such as idiopathic low back pain, disc herniation,
      radiculopathy, myelopathy, and spinal stenosis. The limited available technology
      for the treatment of these and other pathologic and disabling conditions arising
      from DDD is highly invasive (eg, surgical discectomy and fusion), manifesting a
      certain degree of complications and unsatisfactory clinical outcomes. Although
      the precise pathophysiology of DDD remains to be clearly delineated, the
      progressive decline in aggrecan, the primary proteoglycan of the nucleus
      pulposus, appears to be a final common pathway. It has been hypothesized that
      imbalance in the synthesis and catabolism of certain critical extracellular
      matrix components can be mitigated by the transfer of genes to intervertebral
      disc cells encoding factors that modulate synthesis and catabolism of these
      components. The successful in vivo transfer of therapeutic genes to target cells
      within the intervertebral disc in clinically relevant animal models of DDD is one
      example of the rapid progress that is being made towards the development of gene
      therapy approaches for the treatment of DDD. This chapter reviews the ability of
      gene therapy to alter biologic processes in the degenerated intervertebral disc
      and outlines the work needed to be done before human clinical trials can be
      contemplated.

PMID- 14724682
TI  - Gene therapy approaches for osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders that
      affect connective tissue integrity. The hallmark of OI is bone fragility,
      although other manifestations, which include osteoporosis, dentigenesis
      imperfecta, blue sclera, easy bruising, joint laxity and scoliosis, are also
      common among OI patients. The severity of OI ranges from prenatal death to mild
      osteopenia without limb deformity. Most forms of OI result from mutations in the
      genes that encode either the proalpha1or proalpha2 polypeptide chains that
      comprise type I collagen molecules, the major structural protein of bone.
      Treatment depends mainly on the severity of the disease with the primary goal to
      minimize fractures and maximize function. Current treatments include surgical
      intervention with intramedullarly stabilization and the use of prostheses.
      Pharmacological agents have also been attempted with limited success with the
      exception of recent use of bisphosphonates, which have been to shown to have some
      effect. Since OI is a genetic disease, these agents are not expected to alter the
      course of the collagen mutations. Cell and gene therapies as potential treatments
      for OI are therefore currently being actively investigated. The design of gene
      therapies for OI is however complicated by the genetic heterogeneity of the
      disease and by the factor that most of the OI mutations are dominant negative
      where the mutant allele product interferes with the function of the normal
      allele. The present review will discuss the molecular changes seen in OI, the
      current treatment options and the gene therapy approaches being investigated as
      potential future treatments for OI.

PMID- 14724683
TI  - Gene intervention in ligament and tendon: current status, challenges, future
      directions.
AB  - Ligament and tendon injuries are common clinical problems. Healing of these
      tissues occurs, but their properties do not return to normal. This predisposes to
      recurrent injuries, instability and arthritis, loss of motion and weakness. Gene
      therapy offers a novel approach to the repair of ligaments and tendons.
      Introduction of genes into ligaments and tendons using vectors has been
      successful. Marker genes and therapeutic genes have been introduced into both
      tissues with evidence of corresponding functional alterations. In addition, gene
      transfer has been used to manipulate the healing environment, opening the
      possibility of gene transfer to investigate ligament and tendon development and
      homeostasis, in addition to using this technology therapeutically. Several
      factors modulate the 'success' of gene transfer in these tissues.

PMID- 14724684
TI  - Stem cells as vehicles for orthopedic gene therapy.
AB  - Adult stem cells reside in adult tissues and serve as the source for their
      specialized cells. In response to specific factors and signals, adult stem cells
      can differentiate and give rise to functional tissue specialized cells. Adult
      mesenchymal stem cells (MSCs) have the potential to differentiate into various
      mesenchymal lineages such as muscle, bone, cartilage, fat, tendon and ligaments.
      Adult MSCs can be relatively easily isolated from different tissues such as bone
      marrow, fat and muscle. Adult MSCs are also easy to manipulate and expand in
      vitro. It is these properties of adult MSCs that have made them the focus of cell
      mediated gene therapy for skeletal tissue regeneration. Adult MSCs engineered to
      express various factors not only deliver them in vivo, but also respond to these
      factors and differentiate into skeletal specialized cells. This allows them to
      actively participate in the tissue regeneration process. In this review, we
      examine the recent achievements and developments in stem-cell-based gene therapy
      approaches and their applications to bone, cartilage, tendon and ligament tissues
      that are the current focus of orthopedic medicine.

PMID- 14724685
TI  - Osteoarthritis gene therapy.
AB  - Osteoarthritis (OA) is the Western world's leading cause of disability. It is
      incurable, costly and responds poorly to treatment. This review discusses
      strategies for treating OA by gene therapy. As OA affects a limited number of
      weight-bearing joints and has no major extra-articular manifestations, it is well
      suited to local, intra-articular gene therapy. Possible intra-articular sites of
      gene transfer include the synovium and the cartilage. Most experimental progress
      has been made with gene transfer to synovium, a tissue amenable to genetic
      modification by a variety of vectors, using both in vivo and ex vivo protocols.
      The focus so far has been upon the transfer of genes whose products enhance
      synthesis of the cartilaginous matrix, or inhibit its breakdown, although there
      is certainly room for alternative targets. It is possible to build a convincing
      case implicating interleukin-1 (IL-1) as a key mediator of cartilage loss in OA,
      and the therapeutic effects of IL-1 receptor anatagonist (IL-1Ra) gene transfer
      have been confirmed in three different experimental models of OA. As transfer of
      IL-1Ra cDNA to human arthritic joints has already been accomplished safely, we
      argue that clinical studies of intra-articular IL-1Ra gene transfer in OA are
      indicated and should be funded. Of the available vector systems, recombinant
      adeno-associated virus may provide the best combination of safety with in vivo
      delivery using current technology.

PMID- 14724686
TI  - Regional gene therapy to enhance bone repair.
AB  - Gene therapy presents a novel approach to the treatment of challenging bone loss
      problems. Recombinant, osteogenic growth factors are now available to enhance
      bone repair, particularly in those applications related to the treatment of
      fracture nonunions and the enhancement of fusion of the spine. However, there is
      concern that a single dose of an exogenous protein will not induce an adequate
      osteogenic signal in many patients, particularly in those cases where there is
      compromise of host bone and the surrounding soft tissue. Transfer of genes
      encoding osteogenic proteins has the potential to overcome the delivery problems
      associated with the use of the proteins themselves. Bone healing is an attractive
      application for gene therapy, because long-term protein production is not
      necessary for many bone repair problems. Therefore, the development of gene
      therapy strategies to treat bone repair problems promises to be easier than the
      application of gene therapy to treat chronic diseases. The purpose of this review
      is to highlight the advantages, disadvantages and clinical potential of various
      gene therapy strategies to enhance bone repair.

PMID- 14724687
TI  - MicroPET imaging of Cre-loxP-mediated conditional activation of a herpes simplex
      virus type 1 thymidine kinase reporter gene.
AB  - Site-specific recombination tools such as the Cre-loxP system are used to create
      animal models where conditional gene deletion/activation studies are required. In
      the current proof of principle study, we have demonstrated that a PET reporter
      gene (PRG), the herpes simplex virus type 1 thymidine kinase (HSV1-tk), can be
      made to remain silent and can be activated by Cre-loxP-mediated recombination in
      cell culture and in living mice. An adenovirus carrying a silent HSV1-tk was tail
      vein injected (1 x 10(9) PFU) in six transgenic mice that express Cre recombinase
      in their liver (Cre+) and in four control mice (Cre-). The liver-specific
      expression of the PRG in Cre+ mice was detected in the microPET following
      injection of the reporter probe, 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine
      ([(18)F]-FHBG). The [(18)F]-FHBG accumulation in the liver in terms of percent
      injected dose per gram of tissue was 7.72+/-1.13 for the Cre+ mice and 0.10+/
      0.02 for the Cre- mice (P<0.05) 48 h after adenoviral injection. These results
      were further validated by quantitative RT-PCR, western blotting and by in vitro
      assays for herpes simplex virus type 1 thymidine kinase enzyme activity. Thus by
      using the Cre-loxP system it is possible to modulate a PRG and noninvasively
      monitor the extent of Cre-loxP-mediated gene activation by imaging in a microPET
      scanner.

PMID- 14724688
TI  - Protective effects of IL-1Ra or vIL-10 gene transfer on a murine model of wear
      debris-induced osteolysis.
AB  - The current study evaluated the protective effects of anti-inflammatory cytokine
      gene transfer on osteolysis provoked by orthopedic biomaterial particles using a
      murine model of inflammatory bone loss. A section of bone was surgically
      implanted into an air pouch established on a syngeneic recipient mouse.
      Inflammation was provoked by introduction of ultra-high-molecular-weight
      polyethylene (UHMWPE) particles into the pouch, and retroviruses encoding for
      interleukin-1 receptor antagonist (hIL-1Ra), viral interleukin-10 (vIL-10), or
      LacZ genes were injected. Pouch fluid and tissue were harvested 7 days later for
      histological and molecular analyses. The results indicated that IL-1Ra or vIL-10
      gene transfer significantly inhibited IL-1beta and tumor necrosis factor (TNF)
      expression at both mRNA and protein levels. There were significantly lower mRNA
      expressions of calcitonin receptor and cathepsin K in RNA isolated from hIL-1Ra-
      or vIL-10-transduced pouches than LacZ-transduced and virus-free controls. Both
      anti-inflammatory cytokine gene transfers significantly reduced the mRNA
      expression of M-CSF (70-90%) and RANK (>65%) in comparison with LacZ- and virus
      free controls. Histological examination showed that hIL-1Ra or vIL-10 gene
      transfer dramatically abolished UHMWPE-induced inflammatory cellular infiltration
      and bone pit erosion compared to LacZ-transduced and virus-free controls.
      Histochemical staining revealed significantly fewer osteoclast-like cells in
      samples treated with IL-1Ra or vIL-10 gene transfer. In addition, bone collagen
      content was markedly preserved in the groups with anti-inflammatory cytokine gene
      transfers compared with the other two groups. Overall, retrovirus-mediated hIL
      1Ra or vIL-10 gene transfer effectively protected against UHMWPE-particle-induced
      bone resorption, probably due to the inhibition of IL-1/TNF-induced M-CSF
      production and the consequent osteoclast recruitment and maturation.

PMID- 14724689
TI  - Characterization of HIV-1 vectors with gammaretrovirus envelope glycoproteins
      produced from stable packaging cells.
AB  - We have recently described a novel, stable human immunodeficiency virus type 1
      (HIV-1) vector packaging system, STAR. High-titre HIV-1 vectors bearing
      gammaretrovirus envelopes (Env) are continuously produced from STAR cells. Here
      we compare the properties of such vectors, with the amphotropic murine leukaemia
      virus (MLV-A) Env, a modified gibbon ape leukaemia virus (GALV) Env and two
      modified versions of the cat endogenous retrovirus RD114 Env, produced from STAR
      cells, to transiently produced HIV-1 vectors with vesicular stomatitis virus G
      protein (VSV-G). Our results indicate that gammaretrovirus pseudotypes from STAR
      cells are relatively stable at 37 degrees C and are resistant to inactivation by
      freeze/thaw cycling or incubation with human sera. HIV-1(VSV-G) was, however,
      sensitive to freeze/thaw when harvested in serum-free media and was readily
      inactivated in human sera. Furthermore, the titre of 'gamma-retrovirus'
      pseudotypes, but not HIV-1(VSV-G), could be increased by the use of a combination
      of polybrene and spinoculation. All pseudotypes could be efficiently
      concentrated, but soluble gammaretrovirus Env could act as an inhibitor of
      infection.

PMID- 14724690
TI  - Functional and phenotypic variations in human T cells subjected to retroviral
      mediated gene transfer.
AB  - The insertion of suicide genes in donor T lymphocytes constitutes the basis of
      new approaches aiming at the treatment of the graft-versus-host disease (GVHD), a
      frequent complication in recipients of allogeneic haematopoietic grafts. In this
      study we investigated the impact that the ex vivo manipulation required for the
      retroviral transduction of T cells had on the functionality and differentiation
      of these cells. Compared to fresh T cells, samples that had been subjected to
      standard activation (1 microg/ml of both anti-CD3i and anti-CD28i MoAbs) followed
      by transduction with vectors encoding for the HSV-tk and tNGFR genes maintained
      the proliferative response to an allogeneic stimulus. These cells, however, had a
      significantly lower cytotoxic response to allogeneic cells compared to fresh
      samples. When the concentration of anti-CD3i was reduced to up to 1000-fold (1
      ng/ml), similar T-cell transductions were obtained, while the cytotoxicity of the
      ex vivo manipulated samples was significantly recovered, when assessed either at
      7 or 14 days of culture. In all instances, a similar functionality was observed
      in transduced samples not subjected to immunomagnetic cell sorting, compared to
      purified fractions enriched in NGFR(+) and NFGR(-) cells. The analysis of CD45RA
      and CCR7 markers in samples transduced under standard stimulatory conditions
      showed a differentiation of fresh CD8(+) CD45RA(+)/CCR7(+) naive cells to cells
      having a predominant central CD45RA(-)/CCR7(+) and effector CD45RA(-)/CCR7(-)
      memory phenotype. However, when samples were activated with low doses of anti
      CD3i, a significant population of naive cells became apparent. Although
      activation with high doses of anti-CD3i/anti-CD28i resulted in a similar
      phenotype in both NGFR(+) and NFGR(-) populations, the naive population observed
      in samples activated with low concentrations of anti-CD3i was almost restricted
      to the NGFR(-) population. These results show that reducing the stimulation
      mediated by anti-CD3i in protocols of T-cell retroviral gene transfer
      significantly helps to preserve the cytotoxic capacity of these cells to
      allogeneic cells, without affecting the susceptibility of these cells to the
      retroviral vector. In addition, we observed that modulating the activation of
      transduced T cells implies the generation of changes in the differentiation of
      CD8(+) cells, although we could not establish a direct relationship between the
      CD45RA/CCR7 phenotype of these cells and their cytotoxic reactivity to an
      allogeneic stimulus.

PMID- 14724691
TI  - hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian
      family that is overexpressed in B-cell lymphoid malignancies.
AB  - The family of immune associated nucleotide binding proteins (Ian) is a distinct
      family of GTP-binding proteins conserved in plants, mice, rats and humans that
      are associated with immune functions, suggesting involvement in conserved defense
      mechanisms. Recently, the rat Ian4 (rIan4) was cloned and it appears to be
      identical to the gene Iddm1/lyp responsible for severe lymphopenia and the
      development of insulin-dependent diabetes in the BB-DP rat. Here we describe the
      characterization of a new human member of the Ian family: hIan5. hIan5 is highly
      homologous to rIan4, has a predicted molecular weight of 35 kDa and contains
      distinct G motifs of GTP-binding proteins (G-1 to G-4) in the N-terminus. Human
      Ian5 is anchored to the mitochondria by the hydrophobic COOH-terminal domain.
      Human Ian5 is highly expressed in lymph node and spleen. Different blood
      fractions show high hIan5 expression in CD4- and CD8-positive T cells and
      monocytes, but not in B lymphocytes. In contrast, in B-CLL (chronic lymphocytic
      leukemia) and mantle cell lymphoma samples, hIan5 mRNA was upregulated. The
      current data underline the role of hIan5 in T-lymphocyte development and
      function, and for the first time suggest that upregulation of Ian proteins is
      associated with B-cell malignancy, possibly by inhibiting apoptosis.

PMID- 14724692
TI  - A two-stage study on multiple sclerosis susceptibility and chromosome 2q33.
AB  - We have performed a two-stage study to analyse the association of polymorphism on
      chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in
      stage-1 in 134 Finnish MS families and the observed associations were tested in
      stage-2 in 186 MS families. We did not find previously reported allelic or
      haplotype associations with CTLA4. We obtained a weak signal of two distinct
      predisposing genes, one proximal the other distal of CTLA4. The putative proximal
      gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02
      and 0.02) and the other distal gene was associated with D2S1271 in families from
      a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM
      distance and the lack of linkage disequilibrium between these loci, we conclude
      that the two association signals are independent. Our results provide preliminary
      evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.

PMID- 14724693
TI  - Effects of simvastatin on pro-inflammatory cytokines in patients with
      hypercholesterolemia.
AB  - BACKGROUND: The role of inflammation in the development of atherosclerosis and
      its complications has been recently documented. Pro-inflammatory cytokines are
      among many postulated factors. It is possible that the imbalance between
      protective cytokines and cytokines affecting endothelial function is one of the
      underlying mechanisms of myocardial ischaemia. AIM: To examine the effects of
      simvastatin on IL-2 and TNFalpha levels in patients with hypercholesterolemia.
      METHODS: The study group consisted of 64 males (age 20-65 years) with
      hypercholesterolemia. The control group was composed of 10 healthy male
      volunteers (age 25-40 years) with normal lipid profile. Total cholesterol, LDL
      cholesterol, IL-2 and TNFalpha were measured in both groups at baseline, after
      three months of dietary treatment, and after a further three months of
      simvastatin therapy. RESULTS: Simvastatin caused a significant decrease in the
      total and LDL-cholesterol levels compared both with baseline measurements
      (p=0.0001) and after dietary treatment (p=0.0001). Moreover, simvastatin
      significantly reduced the IL-2 plasma concentration (p=0.0003). There were no
      significant differences between IL-2 levels before and following dietary
      treatment. The TNFalpha serum concentration significantly decreased following the
      implementation of diet (p=0.0001). Subsequent simvastatin therapy caused further
      decrease in the TNFalpha serum concentration but this difference did not achieve
      statistical significance. CONCLUSIONS: A hypolipemic diet significantly decreases
      TNFalpha serum concentration without affecting the IL-2 level. The subsequent
      simvastatin therapy significantly reduces IL-2 but not TNFalpha when compared
      with the post-diet values.

PMID- 14724694
TI  - Increased carotid artery intima-media thickness as an indicator of the onset of
      atherosclerosis in patients with connective tissue systemic diseases.
AB  - BACKGROUND: Systemic connective tissue diseases have an autoimmunological
      background. Atherosclerosis is the main cause of ischaemic heart disease in
      patients with these disorders, particularly in young females. Atherosclerotic
      process begins in the intimal and medial layers of arterial wall. Early detection
      of these changes may have important clinical implications. AIM: To assess the
      intima-media thickness (IMT) in carotid arteries in patients with connective
      tissue disorders and to correlate IMT with the presence of antiphospholipid (aPL)
      antibodies. METHODS: The study group consisted of 74 patients (63 females, 11
      males) with documented connective tissue disease and 75 (62 females, 13 males)
      control subjects without clinical symptoms suggesting atherosclerosis. The IMT
      values, measured using ultrasonography, and aPL (IgG and IgM) antibody titre were
      assessed in all subjects. RESULTS: Mean aPL IgG and IgM values were significantly
      higher in patients than in controls (9.22 GMP/ml vs 6.59 GMP/ml, p<0.01; and
      18.59 MPL/ml vs 12.05 MPL/ml, p<0.01, respectively). Patients with connective
      tissue diseases had significantly higher IMT values than controls (0.82 mm vs
      0.57 mm, p<0.01). The IMT values positively correlated with age, presence of aPL
      antibodies, hypercholesterolemia and duration of the disease. CONCLUSIONS: The
      presence of aPL antibodies and increased IMT may indicate atherosclerosis in
      young patients with connective tissue diseases, and identify those who need more
      intensive prophylactic treatment in order to decrease the risk of atherosclerosis
      related complications and death.

PMID- 14724695
TI  - Aortic regurgitation in adults after surgical repair of tetralogy of Fallot.
AB  - BACKGROUND: Total surgical repair of tetralogy of Fallot is usually associated
      with a favourable long-term outcome. However, complications or consequences of
      the defect such as dilatation of aortic root and aortic regurgitation are present
      in some patients. AIM: To assess the prevalence of aortic regurgitation in
      relation to the timing of surgery and preceding palliative procedures as well as
      to examine its effects on left ventricular (LV) dimensions in adults after
      surgical repair of tetralogy of Fallot. METHODS: The study group consisted of 63
      patients in the mean age of 25.6+/-6.5 years who underwent surgery at the mean
      age of 7.4 years (mean 17.2 years ago). Echocardiographic assessment of the
      thickness of the inter-ventricular septum, posterior LV wall, end-diastolic LV
      diameter, left atrial dimension and aortic root diameter was performed. Aortic
      incompetence was examined using a colour Doppler method. RESULTS: Aortic
      incompetence was found in 13 (20%) patients. Only four of them had undergone a
      palliative procedure prior to the repair of the defect. Patients with aortic
      regurgitation had significantly greater aortic root dimension (p=0.001), LV
      diameter (p=0.05) and were significantly older (p=0.005) than patients without
      aortic incompetence. A significant correlation was found between aortic root
      diameter and current age (p=0.02). A significant correlation was also observed
      between LV diameter and time elapsed after surgery (p=0.001), and between left
      atrial dimension and patients' current age (p=0.02) as well as time from the
      repair of the defect (p=0.003). CONCLUSIONS: 1. Minor aortic regurgitation and LV
      dilatation are present in 20% of adults who underwent repair of tetralogy of
      Fallot. 2. Aortic regurgitation is present in those who have dilated aortic root.
      3. Aortic regurgitation is not associated with palliative surgery performed in
      the past. 4. Aortic regurgitation is more frequent in the elderly but is not
      associated with patient's age at surgery or time elapsed since repair.

PMID- 14724696
TI  - Percutaneous autologous myoblast transplantation in the treatment of post
      infarction myocardial contractility impairment--report on two cases.
AB  - Numerous animal experimental studies as well as the initial human experience have
      shown that autologous skeletal myoblast transplantation into area of post
      infarction left ventricular injury results in an increase in segmental
      contractile performance related to contraction of cells differentiated from
      transplanted myoblasts. We have previously introduced skeletal myoblast
      transplantation performed at the time of coronary artery bypass grafting.
      Currently, we report the first two cases in Poland of percutaneous autologous
      myoblast transplantation in the treatment of post-infarction heart failure. The
      procedures were performed using a catheter system enabling intra-myocardial
      injections from the lumen of cardiac veins under intravascular ultrasound
      guidance. Lack of major procedural complications and expected benefits from
      myocardial regeneration in patients with post-infarction heart failure justify
      initiation of phase one clinical trial to evaluate this method.

PMID- 14724697
TI  - Autologous bone marrow stem cell transplantation in acute myocardial infarction
      report of two cases.
AB  - The results of numerous experimental and clinical studies evaluating
      transplantation of bone marrow-derived pluripotential stem cells into the area of
      postinfarction myocardial injury, including direct myocyte precursors, are very
      encouraging. We have previously reported our clinical experience with
      transplantation of autologous skeletal myoblasts in the treatment of
      postinfarction myocardial injury. Currently, we report on two cases of
      intracoronary autologous bone marrow - derived CD34+ stem cells transplantation
      during acute phase of myocardial infarction. Lack of major procedural
      complication and expected benefits resulting from myocardial regeneration justify
      the initiation of a clinical study evaluating the use of this method in the
      treatment of patients with myocardial infarction. Our current report is only a
      method description and the two first cases presentation, indicating its
      feasibility - evaluation of the efficacy requires future investigations.

PMID- 14724698
TI  - [Renal artery aneurysm as a cause of resistant hypertension in a young female-
      case report].
AB  - A case of a 19-year-old woman suffering for 5 years from pharmacologically
      resistant hypertension, is presented. During invasive diagnostic procedures left
      renal artery aneurysm was found. Surgical resection with vessel prosthesis
      implantation was successfully performed. Examination carried-out 6 months later
      revealed good response to pharmacological treatment with normal levels of blood
      pressure.

PMID- 14724699
TI  - [Subclavian-coronary steal syndrome following CABG--a case report].
AB  - A case of 47-year-old man with occlusion of the subclavian artery occurring few
      months after CABG with the left internal mammary artery grafting is presented.
      The patient developed a subclavian-coronary steal syndrome with retrograde blood
      flow from the coronary circulation to the subclavian artery through the left
      internal mammary artery. Clinical presentation consisted of vertigo and
      recurrence of chest pain. The increasing frequency of this syndrome and the
      preoperative preventive methods such as pressure gradient measurement between the
      left and right upper limb are discussed.

PMID- 14724700
TI  - [Transcatheter closure of wide, patent ductus arteriosus in an adult patient with
      severe pulmonary hypertension-a case report].
AB  - A case of a 49-year-old female with patent ductus arteriosus complicated by
      severe pulmonary hypertension is presented. The patent ductus arteriosus was
      successfully closed by the Amplatzer duct occluder. The physical capacity
      improved from functional NYHA class III at baseline to class I one month after
      the procedure. A significant reduction of systolic blood pressure in the
      pulmonary artery and pulmonary resistance was also observed. Indications for
      transcatheter closure of the patent ductus arteriosus in patients with severe
      pulmonary hypertension are discussed.

PMID- 14724701
TI  - [The role of antioxidant vitamins C and E in cardiovascular therapy].

PMID- 14724702
TI  - [Depression as a risk factor of cardiovascular diseases].

PMID- 14724703
TI  - [The role of depression in cardiovascular disorders. Focus on ischaemic heart
      disease].

PMID- 14724711
TI  - [Pulmonary valve stenosis].

PMID- 14724712
TI  - [Electrocardiogram of the month].

PMID- 14724713
TI  - [Angiogram of the month].

PMID- 14724714
TI  - [Successful ablation of focal atrial fibrillation eliminates syncope caused by
      conduction and automaticity disturbances--reverse remodeling of SA an AV nodes
      function].

PMID- 14724717
TI  - Screening for left ventricular systolic dysfunction: the use of B-type
      natriuretic peptide.
AB  - Congestive heart failure (CHF) is a disease condition that is increasing in
      prevalence and is associated with significant morbidity and mortality. Left
      ventricular systolic dysfunction (LVSD) is a treatable precursor of CHF, but
      remains asymptomatic in about half of the individuals afflicted. This observation
      has spurred interest in screening for LVSD. Plasma B-type natriuretic peptide
      (BNP) is a widely accepted test for the diagnosis of overt CHF. In this review,
      we examine the potential role for plasma BNP as a screening tool for asymptomatic
      LVSD. The performance of any screening test depends on its accuracy, the
      prevalence of the disease condition screened for, and the availability of
      resources for follow-up of individuals in whom the disease was detected. In the
      context of community-wide screening for LVSD, a test with high specificity would
      be important so as to minimize the costs of expensive definitive follow-up tests
      (i.e. echocardiography). The prevalence of significant LVSD (ejection fraction
      20.40) is low, limiting the enthusiasm for a screening program targeting the
      general population. This is especially true for women, in whom the condition is
      rare, and the performance characteristics of plasma BNP are sub-optimal. In men,
      plasma BNP may be a useful screening test in high-risk individuals in whom there
      are no other clinical indications for echocardiography. The choice of the
      appropriate plasma BNP threshold that triggers further work-up in such high-risk
      individuals may vary according to the availability of resources, and with the
      healthcare priorities of a community.

PMID- 14724718
TI  - Beta-blocker use in patients with congestive heart failure and concomitant
      obstructive airway disease: moving from myth to evidence-based practice.
AB  - Beta-adrenergic blocking agents, or beta-blockers, are indicated in the
      management of angina pectoris, myocardial infarction, hypertension, congestive
      heart failure (CHF), cardiac arrhythmias, and thyrotoxicosis, and are given to
      reduce perioperative complications. Despite clear evidence that they reduce
      morbidity and mortality, clinicians are often hesitant to administer them for
      fear of adverse reactions. Over the past several years, many of the
      contraindications traditionally listed for betablockers have been questioned and
      disproved. Beta-blockers were contraindicated in CHF because of their intrinsic
      negative inotropic activity, but have now been shown to be beneficial, partly due
      to their ability to enhance sensitivity to sympathetic stimulation. Beta-blockers
      have also been contraindicated for patients with obstructive lung diseases, such
      as asthma and chronic obstructive pulmonary disease, due to the potential risk
      for bronchospasm. However, new evidence has shown that cardioselective beta
      blockers are safe in patients with obstructive lung diseases, and may actually be
      beneficial by enhancing sensitivity to endogenous or exogenous beta-adrenergic
      stimulation. This article will review the evidence concerning the safety of beta
      blocker use in patients with CHF and concomitant obstructive lung disease, with
      specific attention to tracking the transition from myth to evidence- based
      practice.

PMID- 14724719
TI  - Left ventricular remodeling: pathophysiology and treatment.
AB  - Left ventricular (LV) remodeling, which can result from myocardial damage or
      ventricular pressure or volume overload, has genomic, cellular, and interstitial
      components with associated changes in ventricular size, shape, wall thickness,
      and function. It is a process that is detectable and measurable clinically,
      generally progressive, and associated with adverse outcomes. However, it is
      amenable to intervention, prevention, or reversal. Following myocardial
      infarction (MI), LV remodeling is particularly likely in patients with transmural
      or anterior infarction and in those with failed reperfusion or LV failure.
      Infarct artery patency and neurohormonal blockade are key management
      considerations for prevention or reversal of LV remodeling. Combination treatment
      with angiotensin-converting enzyme inhibition and beta-blockade is of proven
      benefit following MI, improving LV remodeling and long-term outcomes.

PMID- 14724720
TI  - Management of scoliosis.
AB  - The etiology and nature of truncal deformity in idiopathic scoliosis remains
      unclear. Only 2 methods are effective to halt or correct the spinal deformity.
      The first is bracing in young patients and the second is surgical correction for
      severe curve. Bracing is feasible for children with a Cobb angle between 20
      degrees to 35 degrees, while surgical correction is the only choice if the Cobb
      angle is greater than 40 degrees. Recent surgical developments have led to good
      correction results with reduced operative scale through continuous spinal cord
      monitoring, evolution of spinal implants, and better perioperative and
      postoperative care. The newer spinal systems can produce 3-dimensional
      reconstruction of the deformity and maintain truncal balance afterwards. The
      newer implants are user-friendly and low-profile. The combined hook/screw
      application (hybrid) and the all-screw placement methods have become quite
      popular. With these methods, the correction rate is increased with reduced loss
      of correction at follow-up. Navigation systems facilitate accurate insertion of
      pedicle screws into the vertebral bodies, while video-assisted endoscopic
      instruments allow early ambulation. These methods are useful in cases of thoracic
      scoliosis. In the future, in order to minimize the operative scale and prevent
      deformity, important goals are elucidation of the real nature and the causes of
      scoliosis and restriction of the number of fusion levels by use of emerging
      technologies.

PMID- 14724721
TI  - Implications of prolonged pause in patients with chronic atrial fibrillation with
      mitral valve disease undergoing atrial compartment operation.
AB  - BACKGROUND AND PURPOSE: Prolonged pause is commonly seen in patients with atrial
      fibrillation (AF), but the electrophysiologic mechanism and clinical importance
      of this phenomenon are not clear. This study examined the incidence and clinical
      importance of prolonged pause in patients with chronic AF and mitral valve
      disease before and after AF surgery. METHODS: Holter recordings were made in 53
      mitral valve patients undergoing concomitant valve surgery and atrial compartment
      operation for chronic AF. There were 38 patients (72%) with successful AF
      conversion and 15 patients (28%) with failed AF conversion. Cardiac rhythms
      before and after operation were compared. An R-R interval > or = 2.0 sec was
      defined as prolonged pause. Serum digoxin and potassium concentration were
      determined within 24 hours of Holter monitoring. RESULTS: Before operation,
      prolonged ventricular pause was common during AF in both groups (76% for the
      successful AF conversion group and 73% for the failed AF conversion group, p >
      0.05). There were 62 +/- 77 episodes of prolonged pause in the successful AF
      conversion group and 59 +/- 44 in the failed group (p > 0.05). The longest pause
      lasted 2.47 +/- 0.26 sec in the successful AF conversion group and 2.43 +/- 0.41
      sec in the failed AF conversion group (p > 0.05), with most prolonged pauses
      occurring at night (72% in the successful and 73% in the failed AF conversion
      group, p > 0.05). After conversion to sinus rhythm, only 1 patient (3%) showed an
      episode of prolonged pause (p < 0.001). No patient exhibited atrioventricular
      (AV) block. In patients with successful AF conversion, the maximal heart rate
      decreased from 150 +/- 28 to 126 +/- 17 beats/min (p < 0.001), the minimal heart
      rate increased from 43 +/- 6 to 56 +/- 5 beats/min (p < 0.001), and ventricular
      premature beats (VPB) counts decreased from 599 +/- 935 to 223 +/- 453/24 hours
      (p < 0.05). In contrast, patients with failed AF conversion showed no significant
      changes in the incidence of prolonged pause, maximal and minimal heart rates, and
      VPB counts after operation. None of the patients received pacemaker implantation
      during a mean follow-up period of 42 +/- 11 months in the successful group and 45
      +/- 13 months in the failed AF conversion group. CONCLUSION: We conclude that
      prolonged pause is common in AF with mitral valve disease and does not indicate
      the presence of sinus or AV nodal dysfunction requiring artificial pacing.

PMID- 14724722
TI  - Effect of medical education on quality of life in adult asthma patients.
AB  - BACKGROUND AND PURPOSE: Previous studies revealed that many asthma patients did
      not understand how to manage their disease, which in turn affected their quality
      of life. This study investigated the effect of asthma education on quality of
      life in Taiwanese adults with asthma. METHODS: A before and after quasi
      experimental design was used. A total of 85 asthma patients were recruited from
      the asthma clinic of a medical center in northern Taiwan using purposive
      sampling. Among these patients, 31 were assigned to the experimental group and 54
      to the control group. The experimental group received four 1-hour sessions of
      group education, while the control group received no instruction. Data were
      collected at 2 different stages: enrollment (baseline), and at 1 month after
      enrollment. All subjects completed the Asthma Quality of Life Questionnaire and
      the Asthma General Knowledge Questionnaire for Adults. Data were analyzed using
      independent-samples t test and paired t test. RESULTS: After completing the
      asthma education sessions, the mean scores on asthma knowledge significantly
      increased from 19.65 to 23.06 (p < 0.001) in the experimental group. The mean
      scores for overall quality of life significantly increased from 5.06 to 5.42 (p <
      0.01). The mean scores in the symptom domain and the exposure to environmental
      stimuli domain also significantly increased from 5.07 to 5.46 (p < 0.01) and 4.94
      to 5.52 (p < 0.001) after education. However, the mean scores of the control
      group on the same questionnaire did not change significantly. CONCLUSION: Asthma
      education can significantly improve asthma knowledge and quality of life in adult
      asthma patients.

PMID- 14724723
TI  - Peripheral differential leukocyte counts and subsequent mortality from all
      diseases, cancers, and cardiovascular diseases in Taiwanese.
AB  - BACKGROUND AND PURPOSE: A higher total leukocyte count has been reported to
      predict all-cause mortality in men, but data are limited for this relation in
      women and for the relation between differential leukocyte counts and all-cause
      mortality in both men and women. This study was designed to analyze these
      relationships in Taiwanese. METHODS: A total of 8447 subjects were enrolled from
      participants in a physical check-up program at National Taiwan University
      Hospital from 1995 to 1997. Information on mortality was obtained from a national
      mortality databank that was updated to the end of 2001. Data were analyzed by
      Student's t test and Cox regression analysis. RESULTS: Among the 245 deaths, 88
      were due to cancer and 62 were due to cardiovascular diseases. Cox regression
      analysis revealed an inverse association between lymphocyte count and all-cause
      mortality in the study group as a whole (all subjects, p < 0.01, hazard ratio =
      0.73). This inverse association was mainly due to an inverse association between
      lymphocyte count and cancer mortality (p < 0.05, hazard ratio = 0.64), especially
      the mortality from hepatoma (p = 0.010, hazard ratio = 0.29). The latter hazard
      ratio of 0.29 indicates that, in all subjects, every decrease of 1.0 x 10(9)/L in
      lymphocyte count increased the risk of mortality from hepatoma by 3.45-fold
      during an average follow-up period of 65.5 months. There was a positive
      association between total leukocyte count and all-cause mortality in men (p <
      0.05, hazard ratio = 1.10), mainly due to both the neutrophil and monocyte counts
      having positive associations with the cardiovascular mortality (both p < 0.05,
      hazard ratio = 1.23 and 1.22, respectively). The latter hazard ratio of 1.22
      indicates that, in men, every increase of 0.1 x 10(9)/L in monocyte count
      increased the risk of cardiovascular mortality by 1.22-fold. CONCLUSIONS: In
      Taiwanese adults of both genders, a lower lymphocyte count is associated with
      cancer mortality, especially mortality from hepatoma. In Taiwanese men, higher
      neutrophil and monocyte counts are associated with cardiovascular mortality.

PMID- 14724724
TI  - Severity assessment in acute paraquat poisoning by analysis of APACHE II score.
AB  - BACKGROUND AND PURPOSE: Several methods have been proposed to predict prognosis
      in patients with paraquat poisoning, but all have their limitations. This
      retrospective study evaluated the usefulness of Acute Physiology and Chronic
      Health Evaluation (APACHE) II scores in risk stratification for patients with
      paraquat poisoning. METHODS: Data from 58 adults with a diagnosis of paraquat
      poisoning presenting to a general hospital over a 10-year period were analyzed.
      APACHE II scores were calculated at 24 hours after admission and data on related
      parameters during the first 24 hours were collected for study. RESULTS: The
      overall in-hospital mortality was 72.4% and mortality in the intensive care unit
      was 82.2%. APACHE II scores were higher in non-survivors (n = 42, 23.3 +/- 12.4)
      than in survivors (n = 16, 6.7 +/- 4.1; p < 0.001). All 26 patients (44.8%) who
      received mechanical ventilation died. Of the 32 patients who received
      hemoperfusion, 25 (78.1%) died. Plasma paraquat concentration, estimated ingested
      amount of paraquat, and APACHE II score were significantly higher in non
      survivors than in survivors (p < 0.05 for all comparisons). There were
      significant correlations between APACHE II score and the following variables:
      plasma paraquat concentration, estimated ingested amount of paraquat, and the
      peak values during the first 24 hours after admission for fraction of inspired
      oxygen, alveolar-arterial oxygen gradient, aspartate aminotransferase, alanine
      aminotransferase, blood urea nitrogen, and serum creatinine (p < 0.05 for all
      comparisons). Higher APACHE II score was associated with greater mortality. All
      patients who had an APACHE II score greater than 20 died before discharge.
      CONCLUSIONS: This study has demonstrated that the APACHE II score is positively
      correlated with plasma paraquat concentration and ingested amount of paraquat. An
      APACHE II score of 20 or higher is a good predictor of in-hospital mortality.

PMID- 14724725
TI  - Continuous lateral rotational therapy in the medical intensive care unit.
AB  - BACKGROUND AND PURPOSE: The efficacy of continuous lateral rotational therapy
      (CLRT) for mechanically ventilated patients is not well established. This study
      investigated the effect of CLRT on gas exchange and the incidence of ventilator
      associated pneumonia (VAP) in mechanically ventilated patients in a medical
      intensive care unit (ICU). METHODS: Thirty five mechanically ventilated patients
      in a medical ICU received CLRT for 5 days, while 35 control patients matched for
      age, gender, cause of respiratory failure, and admission Acute Physiology and
      Chronic Health Evaluation (APACHE) score, received routine positional change. The
      results of blood gas analysis, incidence of VAP, findings on chest radiograph,
      length of ICU stay, and sputum characteristics were recorded. RESULTS: Greater
      improvement in oxygenation index (the ratio of arterial partial pressure of
      oxygen to fraction of inspired oxygen) was noted in the patients who received
      CLRT (31 +/- 42 vs 6 +/- 76, p = 0.03). Patients who received CLRT also had lower
      VAP incidence (0 vs 5, p < 0.001), were more likely to have improvement in
      pulmonary infiltrates (17 vs 12, p = 0.04) and had shorter ICU stay (22 +/- 8
      days vs 27 +/- 12 days, p = 0.09). The ICU discharge status (dead, ventilator
      dependent, alive) was not significantly different between the 2 groups.
      CONCLUSION: Mechanically ventilated patients in the medical ICU who received CLRT
      had improved oxygenation and reduced incidence of VAP compared to controls.

PMID- 14724726
TI  - Nevoid basal cell carcinoma syndrome - clinical manifestations and mutation
      analysis of a Taiwanese family.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is a rare pleiotropic autosomal
      dominant disease predominantly characterized by the occurrence of multiple basal
      cell carcinomas, odontogenic keratocysts (OKCs) of the jaw, and other
      developmental defects. Mutations in the human patched gene (PTCH) have recently
      been detected in patients with NBCCS. We report the clinical manifestations of a
      Taiwanese family with NBCCS and mutation analysis of the PTCH gene from
      peripheral blood, OKC tissues, and cyst content. A heterozygous A-to-G transition
      at nucleotide 3169-2 within the intron 18 (3169-2 A>G) was found. The cystic
      membrane and the cystic content showed the same results. Mutation analysis can
      provide a reliable prenatal diagnosis of this syndrome in subsequent pregnancies.

PMID- 14724727
TI  - Total descending thoracic and abdominal aorta grafting in type III aortic
      dissection with aneurysm.
AB  - Single-stage complete replacement of the descending thoracic aorta and the
      abdominal aorta is a surgical challenge. A 65-year-old man developed acute
      DeBakey type IIIB aortic dissection and was treated medically. The affected aorta
      dilated progressively, reaching a maximal diameter of 7 cm 2 years later.
      Computed tomography revealed a Crawford type II thoracoabdominal aortic aneurysm
      and an additional infrarenal abdominal aortic aneurysm below the dissected aorta.
      The descending thoracic aorta and the abdominal aorta were completely replaced
      with a Hemashield graft under deep hypothermic circulatory arrest. The
      postoperative course was complicated with transient left hemiparesis and upper
      gastrointestinal bleeding which were successfully treated by transarterial
      embolization. The results of this case indicate that complete replacement of the
      descending thoracic and abdominal aorta can adequately and safely treat type III
      aortic dissection.

PMID- 14724728
TI  - Oral clodronate therapy for hypercalcemia related to extensive subcutaneous fat
      necrosis in a newborn.
AB  - Hypercalcemia is occasionally found in newborns with subcutaneous fat necrosis
      and carries potential life-threatening risk. Bisphosphonates have been recently
      introduced in the treatment of subcutaneous fat necrosis in newborns. We report a
      case of extensive subcutaneous fat necrosis in a female infant complicated with
      intractable hypercalcemia. Standard treatment for hypercalcemia was given,
      including saline hydration, a low calcium diet, furosemide, and glucocorticoid,
      but without response. Serum 1,25-dihydroxyvitamin D level was elevated at 126
      pg/mL, 25-hydroxyvitamin D level was normal, and intact parathyroid hormone was
      suppressed at < 1 pg/mL. Oral clodronate disodium, a second-generation
      bisphosphonate, was administered, and resulted in the normalization of serum
      calcium, urine N-telopeptide, urine calcium/creatinine ratio, and serum intact
      parathyroid hormone level. This case suggests that oral clodronate may be an
      effective treatment for subcutaneous fat necrosis with hypercalcemia in newborns.

PMID- 14724729
TI  - Therapeutic keratectomy for Mycobacterium abscessus keratitis after LASIK.
AB  - We report successful treatment of a case of Mycobacterium abscessus keratitis
      after laser in situ keratomileusis (LASIK) with therapeutic lamellar keratectomy.
      A 34-year-old woman developed a 2 x 2 mm feathery infiltration within the
      interface inferior to the pupil margin with mild inflammation of the conjunctiva
      in her left eye 40 days after LASIK surgery. Bacterial culture from the
      infiltrates of the interface of the stromal bed revealed Mycobacterium abscessus.
      After combination antibiotic therapy including amikacin and ciprofoxacin was
      given for 6 weeks, infiltration persisted despite the development of necrosis in
      the flap tissue. Therapeutic lamellar keratectomy combined with flap removal was
      performed. No recurrence was found 1 year after the surgery. Therapeutic lamellar
      keratectomy with flap removal can provide an effective treatment modality for the
      management of post-LASIK Mycobacterium abscessus keratitis that is unresponsive
      to medical treatment.

PMID- 14724730
TI  - Wolfram syndrome: phenotype and novel mutation in two Taiwanese siblings.
AB  - Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder.
      The responsible gene, WFS1, was identified in 1998 and over 66 mutations have
      been reported since then. We report 2 siblings in a Taiwanese family with WS.
      They had similar clinical courses, including successive development of diabetes
      mellitus, optic atrophy, diabetes insipidus, hearing impairment, and urological
      complications from age 5 to 15 years. Rapid progression of systemic and
      neurological symptoms was noted in the elder brother. Mutation analysis of the 2
      probands revealed compound heterozygotes of 1 novel and 1 previously reported
      mutation. Their parents and an asymptomatic sibling were carriers of 1 mutation.

PMID- 14724731
TI  - Successful living-related renal transplantation in a 2-year-old girl weighing
      less than 10 kilograms.
AB  - The success of renal transplantation for infants weighing less than 10 kg is very
      limited because of graft thrombosis. We report a successful living-related renal
      transplant in a 2-year-old girl weighing 9.5 kg. Chronic renal failure was
      diagnosed 1 month before the transplantation. Laparoscopic donor nephrectomy was
      performed to retrieve the left kidney of her father, a 36-year-old man weighing
      70 kg, and the recipient operation was conducted via a right retroperitoneal
      approach. The right native kidney of the recipient was removed to accommodate the
      graft kidney during the transplant surgery. The graft renal artery, renal vein,
      and ureter were anastomosed to the recipient abdominal aorta, inferior vena cava,
      and bladder, respectively. The abdominal fascial defect was closed with
      absorbable mesh grafting, and the skin was closed primarily. With intensive fluid
      therapy and monitoring after reperfusion of the graft kidney, the patient
      recovered uneventfully and was discharged with an FK506-based immunosuppressive
      regimen 2 weeks after the operation. Renal function was good, and serum
      creatinine was 0.5 mg/dL 6 months after the operation.

PMID- 14724732
TI  - Serum leptin concentration is linked to chromosomes 2 and 6 in the OLETF rat, an
      animal model of type 2 diabetes with mild obesity.
AB  - Leptin is produced by adipose tissue and acts as a feedback signal to the
      hypothalamus controlling energy homeostasis, by reducing food consumption and
      increasing energy expenditure. Because serum leptin levels are highly correlated
      with body fat mass, they can be used as an index to predict obesity-related
      diseases. However, the identity of genetic factors that influence the obesity and
      the obesity-related metabolic disorders remains largely unknown. In this study,
      we performed a whole-genome scan search, using 382 F2 intercross progeny between
      the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model for obese type
      2 diabetes in human, and F344 rat, in order to identify loci responsible for the
      regulation of leptin and other obesity-related plasma substances. We have
      identified two quantitative trait loci (QTLs) contributing to serum leptin
      levels. These two loci, designated Olep1 [Chromosome (Chr) 2] and Olep2 (Chr 6),
      were homologous to those of human genome regions containing several potential
      candidate genes for obesity. These are fatty acid-binding protein 2 (FABP2),
      FABP4, and FABP5 for Olep1, and proopiomelanocortin (POMC) and glucose regulatory
      protein (GCKR) for Olep2.

PMID- 14724733
TI  - A new mouse limb mutation identifies a Twist allele that requires interacting
      loci on chromosome 4 for its phenotypic expression.
AB  - Pluridigite ( Pdt) is a semi-dominant mutation obtained after a mutagenesis
      experiment with ethyl-nitroso-urea (ENU). The mutant exhibits abnormal skeletal
      pattern formation characterized by the formation of extra digits (polydactyly) in
      the preaxial (anterior) part of the hindlimbs. The phenotype shows incomplete
      penetrance, depending on the genetic background. In an F2 cross with C57BL/6, the
      phenotype could not be associated with a single locus. Strong linkage was
      observed with markers located on Chromosome (Chr) 12, in a 2-cM interval between
      D12Mit136 and D12Mit153. This region contains the Twist gene, and we show that
      the [Pdt] phenotype is dependent upon a new allele of Twist. We further
      identified that the whole Chr 4 is associated with the [Pdt] phenotype. The
      Pluridigite phenotype thus results from the combination of a Twist mutant allele
      and at least two additional loci.

PMID- 14724734
TI  - QTL fine-mapping with recombinant-inbred heterogeneous stocks and in vitro
      heterogeneous stocks.
AB  - We compared strategies to fine-map Quantitative Trait Loci (QTL) in mice with
      heterogeneous stocks (HS). We showed that a panel of about 100 Recombinant Inbred
      Lines (RIL) derived from an HS, and which we called an RIHS, was ideally suited
      to fine-map QTL to very high resolution, without the cost of additional
      genotyping. We also investigated a strategy based on in vitro fertilization of
      large numbers of F(1) offspring of HS males crossed with an inbred line (IVHS).
      This method required some additional genotyping but avoided the breeding delays
      and costs associated with the construction of an RI panel. We showed that QTL
      detection was higher by using RIHS than with IVHS and that it was independent of
      the number of RI lines, provided the total number of animals phenotyped was
      constant. However, fine-mapping accuracy was slightly better with IVHS. We also
      investigated the effects of varying the number of HS generations and using
      multiallelic microsatellites instead of SNPs. We found that quite modest
      generation times of 10-20 generations were optimal. Microsatellites were superior
      to SNPs only when the generation time was 30 or more and when the markers were
      widely spaced.

PMID- 14724735
TI  - Imprinted methylation profiles for proximal mouse chromosomes 11 and 7 as
      revealed by methylation-sensitive representational difference analysis.
AB  - Proximal mouse Chromosome (Chr) 11 shares regions of orthology with the candidate
      gene region for the imprinting growth disorder Silver-Russell syndrome (SRS) on
      human Chr 7p. It has previously been shown that mice with two maternal or two
      paternal copies (duplications, Dp) of proximal Chr 11 exhibit reciprocal growth
      phenotypes. Those with two paternal copies show fetal and placental overgrowth,
      while those with two maternal copies are growth retarded. The growth retardation
      observed in the latter is reminiscent of the intrauterine growth restriction
      (IUGR) observed in SRS patients with maternal uniparental disomy for Chr 7
      (mUPD7). We have carried out a methylation-sensitive representational difference
      analysis (Me-RDA) screen to look for regions of differential methylation (DMRs)
      associated with imprinted genes. For these experiments, we have used mouse
      embryos with uniparental duplications of Chrs 11 and 7 proximal to the breakpoint
      of the reciprocal translocation T(7;11)40Ad. Two previously known imprinted loci
      associated with paternal allele hypomethylation were recovered on proximal mouse
      Chr 11, U2af1-rs1 and Meg1/Grb10. These two genes map 15 cM apart, so it seems
      likely that they are within separate imprinted domains that do not contain
      additional DMRs. The known imprinted gene Peg3, located on mouse proximal Chr 7,
      was also detected in our screen. The finding that Peg3 was differentially
      methylated in embryos with uniparental inheritance of proximal Chr 7 confirms
      that Peg3 is located proximal to the breakpoint of T40Ad in G-band 7A2. Because
      GRB10 has previously been reported to be a candidate gene for SRS, we analysed 22
      patients for epimutations of the GRB10 differentially methylated region that
      could lead to the altered expression of this gene. No such mutations were found.

PMID- 14724737
TI  - Differential expression of genes related to levels of mucosal cell proliferation
      among multiple rat strains by using oligonucleotide microarrays.
AB  - Induction levels of cell proliferation, in response to gastric mucosal damage by
      N-methyl- N'-nitro- N-nitrosoguanidine (MNNG), are different among rat strains
      and correlate with susceptibility to MNNG-induced gastric carcinogenesis. Here,
      we used oligonucleotide microarrays to search for genes that show expression
      levels accordant with the extents of cell proliferation among six rat strains.
      Expression levels of 8,800 probe sets were analyzed in the pylorus of ACI, LEW,
      WKY (strains with strong cell proliferation), F344, (ACI x BUF)F1, and BUF rats
      (strains with weak cell proliferation) after 2-week MNNG treatment. No genes
      showed complete accordance, and 22 genes showed accordance with one or two
      exceptions. After confirmation by quantitative RT-PCR, four genes--cellular
      retinoic acid-binding protein II ( Crabp2), fatty acid binding protein 1 (
      Fabp1), progastricsin (pepsinogen C, Pgc), and UDP-glucuronosyltransferase 2
      family member 5 ( Ugt2b5)--were found to show good accordance with only one
      exception. Crabp2, Fabp1, and Ugt2b5 were differentially expressed between ACI
      and BUF rats both before and after MNNG treatment. Although Crabp2 had been
      identified as one of the 16 genes differentially expressed between ACI and BUF
      rats with cDNA-RDA, Fabp1 and Ugt2b5 were newly identified in this study. All
      three genes are known to be involved in retinoic acid-mediated signaling and
      could be involved in the control of differential induction of cell proliferation.

PMID- 14724736
TI  - Overlapping deletions spanning the proximal two-thirds of the mouse t complex.
AB  - Chromosome deletion complexes in model organisms serve as valuable genetic tools
      for the functional and physical annotation of complex genomes. Among their many
      roles, deletions can serve as mapping tools for simple or quantitative trait loci
      (QTLs), genetic reagents for regional mutagenesis experiments, and, in the case
      of mice, models of human contiguous gene deletion syndromes. Deletions also are
      uniquely suited for identifying regions of the genome containing
      haploinsufficient or imprinted loci. Here we describe the creation of new
      deletions at the proximal end of mouse Chromosome (Chr) 17 by using the technique
      of ES cell irradiation and the extensive molecular characterization of these and
      previously isolated deletions that, in total, cover much of the mouse t complex.
      The deletions are arranged in five overlapping complexes that collectively span
      about 25 Mbp. Furthermore, we have integrated each of the deletion complexes with
      physical data from public and private mouse genome sequences, and our own genetic
      data, to resolve some discrepancies. These deletions will be useful for
      characterizing several phenomena related to the t complex and t haplotypes,
      including transmission ratio distortion, male infertility, and the collection of
      t haplotype embryonic lethal mutations. The deletions will also be useful for
      mapping other loci of interest on proximal Chr 17, including T-associated sex
      reversal ( Tas) and head-tilt ( het). The new deletions have thus far been used
      to localize the recently identified t haplolethal ( Thl1) locus to an
      approximately 1.3-Mbp interval.

PMID- 14724738
TI  - The bovine 5' AMPK gene family: mapping and single nucleotide polymorphism
      detection.
AB  - The 5'-AMP-activated protein kinase (AMPK) family is an ancient stress response
      system whose primary function is regulation of cellular ATP. Activation of AMPK,
      which is instigated by environmental and nutritional stresses, initiates energy
      conserving measures that protect the cell by inhibition and phosphorylation of
      key enzymes in energy-consuming biochemical pathways. The seven genes that
      comprise the bovine AMPK family were mapped in cattle by using a radiation hybrid
      panel. The seven genes mapped to six different cattle chromosomes, each with a
      LOD score greater than 10.0. PRKAA1 mapped to BTA 20, PRKAA2 and PRKAB2 to BTA 3,
      PRKAB1 to BTA 17, PRKAG1 to BTA 5, PRKAG2 to BTA 4, and PRKAG3 to BTA 2. Five of
      the seven genes mapped to regions expected from human/cattle comparative maps.
      PRKAB2 and PRKAG3, however, have not been mapped in humans. We predict these
      genes to be located on HSA 1 and 2, respectively. Additionally, one synonymous
      and one non-synonymous single nucleotide polymorphism (SNP) were detected in
      PRKAG3 in Bos taurus cattle. In an effort to determine ancestral origins, various
      herds of mixed breed cattle as well as other ruminant species were characterized
      for sequence variation in this region of PRKAG3. Owing to the physiological
      importance of this gene family, we believe that its individual genes are
      candidate genes for conferring resistance to diseases in cattle.

PMID- 14724739
TI  - Secreted protein prediction system combining CJ-SPHMM, TMHMM, and PSORT.
AB  - To increase the coverage of secreted protein prediction, we describe a
      combination strategy. Instead of using a single method, we combine Hidden Markov
      Model (HMM)-based methods CJ-SPHMM and TMHMM with PSORT in secreted protein
      prediction. CJ-SPHMM is an HMM-based signal peptide prediction method, while
      TMHMM is an HMM-based transmembrane (TM) protein prediction algorithm. With CJ
      SPHMM and TMHMM, proteins with predicted signal peptide and without predicted TM
      regions are taken as putative secreted proteins. This HMM-based approach predicts
      secreted protein with Ac (Accuracy) at 0.82 and Cc (Correlation coefficient) at
      0.75, which are similar to PSORT with Ac at 0.82 and Cc at 0.76. When we further
      complement the HMM-based method, i.e., CJ-SPHMM + TMHMM with PSORT in secreted
      protein prediction, the Ac value is increased to 0.86 and the Cc value is
      increased to 0.81. Taking this combination strategy to search putative secreted
      proteins from the International Protein Index (IPI) maintained at the European
      Bioinformatics Institute (EBI), we constructed a putative human secretome with
      5235 proteins. The prediction system described here can also be applied to
      predicting secreted proteins from other vertebrate proteomes.

PMID- 14724740
TI  - Passive transport of macromolecules through Xenopus laevis nuclear envelope.
AB  - Although nuclear pore complexes (NPC) are considered to be key structures in gene
      expression, little is known about their regulatory control. In order to explore
      the regulatory mechanism of passive transport of small macromolecules we examined
      the influence of different factors on the diffusional pathway of NPCs in isolated
      Xenopus laevis oocyte nuclei. Diffusion of fluorescence-labeled 10-kD dextran was
      measured across the nuclear envelope with confocal fluorescence microscopy.
      Surprisingly, the filling state of the perinuclear Ca(2+) store had no influence
      on passive transport of 10-kD dextran. Furthermore, nuclear envelope permeability
      was independent of cytoplasmic pH (pH range 8.3-6.3). In contrast, nuclear
      swelling, induced by omission of the endogenous cytosolic macromolecules, clearly
      increased nuclear permeability. An antibody against the glycoprotein gp62,
      located at the central channel entrance, reduced macromolecule diffusion. In
      addition, nuclei from transcriptionally active, early developmental stages (stage
      II) were less permeable compared to transcriptionally inactive, late
      developmental-stage (stage VI) nuclei. In stage II nuclei, atomic force
      microscopy disclosed NPC central channels with plugs that most likely were
      ribonucleoproteins exiting the nucleus. In conclusion, the difference between
      macromolecule permeability and previous measurements of electrical resistance
      strongly indicates separate routes for macromolecules and ions across the nuclear
      envelope.

PMID- 14724741
TI  - Intracellular calcium: a prerequisite for aldosterone action.
AB  - Transport of salt and water in various tissues is under control of the
      mineralocorticoid hormone aldosterone. As a liphophilic hormone, aldosterone
      diffuses through the plasma membrane and, then, binds to cytosolic
      mineralocorticoid receptors in the target cells. After binding to nuclear pore
      complexes, the activated receptor is translocated to the nucleus where
      transcription processes are initiated. After a lag period of about 20 minutes
      hormone-specific early mRNA transcripts leave the nucleus through nuclear pores.
      Some of the steps in this cascade can be followed by electrophysiology in Xenopus
      laevis oocyte nuclei. In addition to the genomic pathway, aldosterone exerts a
      rapid pre-genomic response that involves an increase in intracellular calcium. In
      this study, we tested for the potential role of Ca(2+) in the genomic response of
      the hormone. We measured the electrical resistance across the nuclear envelope in
      response to aldosterone, in presence and absence of intracellular Ca(2+). Nuclear
      envelope electrical resistance reflects receptor binding to the nuclear pore
      complexes ("early" resistance peak, 2 minutes after aldosterone), ongoing
      transcription ("transient" resistance drop, 5-15 minutes after aldosterone) and
      mRNA export ("late" resistance peak, 20 minutes after aldosterone). Pre-injection
      of the Ca(2+) chelator EGTA eliminated all electrical responses evoked by
      aldosterone. The transient resistance drop and the late resistance peak, induced
      by the hormone, were prevented by the transcription inhibitor actinomycin D,
      coinjected with aldosterone, while the early resistance peak remained unaffected.
      We conclude that (i). the presence of intracellular Ca(2+) is a prerequisite for
      the genomic action of aldosterone. (ii). Intracellular calcium plays a role early
      in the signaling cascade, either in agonist-receptor interaction, or receptor
      transport/docking to the nuclear pore complexes.

PMID- 14724742
TI  - Endothelial cell swelling by aldosterone.
AB  - There is accumulating evidence that mineralocorticoids not only act on kidney but
      also on the cardiovascular system. We investigated the response of human
      umbilical venous endothelial cells (HUVECs) to aldosterone at a time scale of 20
      minutes in absence and presence of the aldosterone antagonist spironolactone or
      other transport inhibitors. We applied atomic force microscopy (AFM), which
      measures cell volume and volume shifts between cytosol and cell nucleus. We
      observed an immediate cell volume increase (about 10%) approximately 1 min after
      addition of aldosterone (0.1 micromol/l), approaching a maximum (about 18%) 10
      min after aldosterone treatment. Cell volume returned to normal 20 min after
      hormone exposure. Spironolactone (1 micromol/l) or amiloride (1 micromol/l)
      prevented the late aldosterone-induced volume changes but not the immediate
      change observed 1 min after hormone exposure. AFM revealed nuclear swelling 5 min
      after aldosterone addition, followed by nuclear shrinkage 15 min later. The
      Na(+)/H(+) exchange blocker cariporide (10 micromol/l) was ineffective. We
      conclude: (i). Aldosterone induces immediate (1 min) swelling independently of
      plasma membrane Na(+) channels and intracellular mineralocorticoid receptors
      followed by late mineralocorticoid receptor- and Na(+)-channel-dependent
      swelling. (ii). Intracellular macromolecule shifts cause the changes in cell
      volume. (iii). Both amiloride and spironolactone may be useful for medical
      applications to prevent aldosterone-induced vasculopathies.

PMID- 14724743
TI  - Gap-junctional hemichannels are activated by ATP depletion in human renal
      proximal tubule cells.
AB  - We present evidence suggesting that gap-junctional hemichannels (GJH) may be
      involved in acute ischemic injury of human renal proximal tubule cells (hPT
      cells). Two GJH, from neighboring cells, join to form an intercellular gap
      junction channel (GJC). Undocked GJH are permeable to hydrophilic molecules up to
      1 kDa, and their opening can significantly alter cell homeostasis. Both GJC and
      GJH formed by connexin 43 (Cx43) are activated by dephosphorylation. Hence, we
      tested whether GJH activation during ATP depletion contributes to cell damage in
      renal ischemia. We found that hPT cells in primary culture express Cx43 (RT-PCR
      and Western-blot analysis) at the plasma membrane region (immunofluorescence).
      Divalent-cation removal or pharmacological ATP depletion increased cell loading
      with the hydrophilic dye 5/6 carboxy-fluorescein (CF, 376 Da) but not with
      fluorescein-labeled dextran (>1500 Da). Endocytosis and activation of P2X
      channels were experimentally ruled out. Several GJC blockers inhibited the
      loading elicited by PKC inhibition. Double labeling (CF and propidium iodide)
      showed that both Ca(2+) removal and ATP depletion increase the percentage of
      necrotic cells. Gadolinium reduced both the loading and the degree of necrosis
      during divalent-cation removal or ATP depletion. In conclusion, GJH activation
      may play an important role in the damage of human renal proximal tubule cells
      during ATP depletion. These studies are the first to provide evidence supporting
      a role of GJH in causing injury in epithelial cells in general and in renal
      tubule cells in particular.

PMID- 14724744
TI  - Characterization of a functionally expressed stretch-activated BKca channel
      cloned from chick ventricular myocytes.
AB  - We have characterized electrophysiological and pharmacological properties of a
      stretch-activated BKca channel (SAKcaC) that was cloned from cultured chick
      ventricular myocytes (CCVM) and expressed in chinese hamster ovary cells (CHO)
      using the patch-clamp technique. Our results indicate that the cloned SAKcaC
      keeps most of the key properties of the native SAKcaC in CCVM, such as
      conductance, ion selectivity, pressure-, voltage- and Ca(2+)-dependencies.
      However, there was a slight difference between these channels in the effects of
      channel blockers, charybdotoxin (CTX) and gadolinium (Gd(3+)). The native SAKcaC
      was blocked in an all-or-none fashion characterized as the slow blockade, whereas
      the conductance of the cloned SAKcaC was gradually decreased with the blockers'
      concentration, without noticeable blocking noise. As the involvement of some
      auxiliary components was suspected in this difference, we cloned a BK beta
      subunit from CCVM and coexpressed it with the cloned SAKcaC in CHO cells to
      examine its effects on the SAKcaC. Although the pharmacological properties of the
      cloned SAKcaC turned out to be very similar to the native one by the
      coexpression, it also significantly altered the key characteristics of SAKcaC,
      such as voltage- and Ca(2+)-dependencies. Therefore we concluded that the native
      SAKca in CCVM does not interact with the corresponding endogenous beta-subunit.
      The difference in pharmacological properties between the expressed SAKcaC in CHO
      and the native one in CCVM suggests that the native SAKca in CCVM is modulated by
      unknown auxiliary components.

PMID- 14724745
TI  - Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293
      cells by acidic di-aryl-ureas.
AB  - The endogenous volume-regulated anion channel (VRAC) from HEK293 cells was
      pharmacologically characterized using the whole-cell patch-clamp technique. Under
      isotonic conditions a small (1.3 nS), Ca(2+)-independent Cl conductance was
      measured. However, swelling at 75% tonicity activated a VRAC identified as an
      outward-rectifying anion current ( P(l) > P(Cl) > P(gluconate)), which was ATP
      dependent and showed inactivation at positive potentials. Activation of this
      current followed a sigmoid time course, reaching a plateau conductance of 42.6 nS
      after 12-15 min ( t(1/2) = 7 min). The pharmacology of this VRAC was investigated
      using standard Cl(-)-channel blockers (NPPB, DIDS, and tamoxifen) as well as a
      new group (acidic di-aryl ureas) of Cl(-)-channel blockers (NS1652, NS3623,
      NS3749, and NS3728). The acidic di-aryl ureas were originally synthezised for
      inhibition of the human erythrocyte Cl(-) conductance in vivo. NS3728 was the
      most potent VRAC blocker in this series ( IC(50) = 0.40 micro M) and even more
      potent than tamoxifen (2.2 micro M). NS3728 accelerated channel inactivation at
      positive potentials. These results show that acidic di-aryl ureas constitute a
      promising starting point for the synthesis of potent inhibitors of VRAC.

PMID- 14724746
TI  - Suppression of calcium sparks in rat ventricular myocytes and direct inhibition
      of sheep cardiac RyR channels by EPA, DHA and oleic acid.
AB  - The anti-arrhythmic effects of long-chain polyunsaturated fatty acids (PUFAs) may
      be related to their ability to alter calcium handling in cardiac myocytes. We
      investigated the effect of eicosapentanoic acid (EPA) and docosahexaenoic acid
      (DHA) on calcium sparks in rat cardiac myocytes and the effects of these PUFAs
      and the monounsaturated oleic acid on cardiac calcium release channels (RyRs).
      Visualization of subcellular calcium concentrations in single rat ventricular
      myocytes showed that intensity of calcium sparks was reduced in the presence of
      EPA and DHA (15 micro M). It was also found that calcium sparks decayed more
      quickly in the presence of EPA but not DHA. Sarcoplasmic vesicles containing RyRs
      were prepared from sheep hearts and RyR activity was determined by either
      [(3)H]ryanodine binding or by single-channel recording. Bilayers were formed from
      phosphatidylethanolamine and phosphatidylcholine dissolved in either n-decane or
      n-tetradecane. EPA inhibited [(3)H]ryanodine binding to RyRs in SR vesicles with
      K(I) = 40 micro M. Poly- and mono-unsaturated free fatty acids inhibited RyR
      activity in lipid bilayers. EPA (cytosolic or luminal) inhibited RyRs with K(I)
      =32 micro M and Hill coefficient, n(1) = 3.8. Inhibition was independent of the n
      alkane solvent and whether RyRs were activated by ATP or Ca(2+). DHA and oleic
      acid also inhibited RyRs, suggesting that free fatty acids generally inhibit RyRs
      at micromolar concentrations.

PMID- 14724747
TI  - Interpretation and optimization of absorbance and fluorescence signals from
      voltage-sensitive dyes.
AB  - Voltage-sensitive dyes produce absorbance and fluorescence changes that can be
      used to image voltage. The present study develops a systematic approach to the
      optimization of these signals. A mathematical analysis assesses the dye optical
      density ( OD) that optimizes the signal-to-noise ratio in absorbance and
      fluorescence measurements. The signal-to-noise ratio is maximal for a dye OD of 2
      (natural logarithm) in absorbance and ~1 in fluorescence. The fluorescence result
      is approximate because, in contrast to absorbance, the optimal dye OD varies with
      the amount of scattering and intrinsic absorbance of the tissue. The signal-to
      noise ratio of absorbance is higher in thick preparations such as brain slices;
      fluorescence is superior in thin preparations such as cell culture. The optimal
      OD for absorbance and fluorescence, as well as the superiority of absorbance,
      were confirmed experimentally on hippocampal slices. This analysis also provided
      insight into the interpretation of signals normalized to resting light
      intensities. With both absorbance and fluorescence, the normalized signal (Delta
      I/I) varies with OD, and does not reflect the change in dye absorbance. In
      absorbance this problem is remedied by dividing Delta I/I by the dye OD to obtain
      the absorbance change. For fluorescence a correction is possible, but is more
      complicated. Because this analysis indicates that high levels of stain optimize
      the signal-to-noise, dyes were tested for pharmacological actions and
      phototoxicity. The absorbance dye RH155 was found to have pharmacological action
      at high staining levels. The fluorescent dye RH414 was phototoxic. Adverse
      effects could not be detected with the absorbance dye RH482.

PMID- 14724748
TI  - Pulses of cell Ca(2+) and the dynamics of tight junction opening and closing.
AB  - A mathematical modeling of tight junction (TJ) dynamics was elaborated in a
      previous study to better understand the dynamics of TJ opening and closing, as
      well as oscillations of TJ permeability that are observed in response to changes
      of extracellular Ca(2+) levels. In this model, TJs were assumed to be
      specifically controlled by the Ca(2+) concentration levels at the extracellular
      Ca(2+) binding sites of zonula adhaerens. Despite the fact that the model
      predicts all aspects of TJ dynamics, we cannot rule out the likelihood that
      changes of intracellular Ca(2+) concentration (Ca(2+) (cell)), which might result
      from changes ? of extracellular Ca(2+) concentration (Ca(2+) (extl)), contribute
      to the observed results. In order to address this aspect of TJ regulation, fast
      Ca(2+)-switch experiments were performed in which changes of Ca(2+) (cell) were
      induced using the Ca(2+) ionophore A23187 or thapsigargin, a specific inhibitor
      of the sarco-endoplasmic reticulum Ca(2+)-ATPase. The results indicate that the
      ionophore or thapsigargin per se do not affect basal tissue electrical
      conductance ( G), showing that the sealing of TJs is not affected by a rise in
      Ca(2+) (cell). When TJs were kept in a dynamic state, as partially open
      structures or in oscillation, conditions in which the junctions are very
      sensitive to disturbances that affect their regulation, a rise of Ca(2+) (cell)
      never led to a decline of G, indicating that a rise of Ca(2+) (cell) does not
      trigger per se TJ closure. On the contrary, always the first response to a rise
      of Ca(2+) (cell) is an increase of G that, in most cases, is a transient
      response. Despite these observations we cannot assure that a rise of Ca(2+)
      (cell) is without effect on the TJs, since an increase of Ca(2+) (cell) not only
      causes a transient increase of G but, in addition, during oscillations a rise of
      Ca(2+) (cell) induced by the Ca(2+) ionophore transiently halted the oscillatory
      pattern of TJs. The main conclusion of this study is that TJ closure that is
      observed when basolateral Ca(2+) concentration (Ca(2+) (bl)) is increased after
      TJs were opened by Ca(2+) (bl) removal cannot be ascribed to a rise of Ca(2+)
      (cell) and might be a consequence of Ca(2+) binding to extracellular Ca(2+)
      sites.

PMID- 14724749
TI  - Human adipose cells have voltage-dependent potassium currents.
AB  - The whole-cell patch-clamp method was used to study the membrane electrical
      properties of human adipocyte cells obtained by differentiating from precursors
      of human abdominal and mammary tissues. All differentiated cells exhibited
      outward currents with sigmoidal activation kinetics. The outward currents showed
      activation thresholds between -20 to -30 mV and slow inactivation. The ionic
      channels underlying the macroscopic current were highly selective for K(+). Their
      selectivity was for typical K(+) channels with relative permeabilities of
      K(+)>NH4+>Cs(+)>Na(+). No evidence of any other type of voltage-gated channel was
      found. The potassium currents ( I(KV)) were blocked reversibly by
      tetraethylammonium and barium. The IC(50) value and Hill coefficient of
      tetraethylammonium inhibition of I(KV) were 0.56 m M and 1.17 respectively. These
      results demonstrate that human adipose cells have voltage-dependent potassium
      currents.

PMID- 14724750
TI  - Soft picture of lateral heterogeneity in biomembranes.
AB  - Standard methods of characterization of electron paramagnetic resonance (EPR)
      spectra of spin-labeled biomembranes limit the resolution of lateral
      heterogeneity to only two or three domain types. This disables examination of the
      structure-function relationship in complex membranes, which might be composed of
      a larger number of different domain types. To enable exploration of this kind, a
      new approach based on analysis of EPR spectra with multi-run, hybrid evolutionary
      optimization is proposed here. From the multiple runs a quasi-continuous
      distribution of membrane spectral parameters (order parameter, proportion of
      spectral component, polarity correction factor, rotational correlation time and
      broadening constant) can be constructed and presented by a new presentation
      technique CODE (colored distribution of E PR spectral parameters). Through this
      the concept of a "soft" picture of membrane heterogeneity is introduced, in
      contrast to the standard "discrete" domain picture. The "soft" characterization
      method, established on synthetic spectra, was used to examine the lateral
      heterogeneity of liposome membranes as well as of membranes of neutrophils from
      healthy and asthmatic horses. In liposome membranes the determined number of
      domain types was the same as already established by standard procedures of EPR
      spectra line-shape interpretation. In membranes of neutrophils a quasi-continuous
      distribution of membrane domain properties was detected by the new method.

PMID- 14724751
TI  - Molecular cloning and expression of a Kv1.1-like potassium channel from the
      electric organ of Electrophorus electricus.
AB  - Electrocytes from the electric organ of Electrophorus electricus exhibited sodium
      action potentials that have been proposed to be repolarized by leak currents and
      not by outward voltage-gated potassium currents. However, patch-clamp recordings
      have suggested that electrocytes may contain a very low density of voltage-gated
      K(+) channels. We report here the cloning of a K(+) channel from an eel electric
      organ cDNA library, which, when expressed in mammalian tissue culture cells,
      displayed delayed-rectifier K(+) channel characteristics. The amino-acid sequence
      of the eel K(+) channel had the highest identity to Kv1.1 potassium channels.
      However, different important functional regions of eel Kv1.1 had higher amino
      acid identity to other Kv1 members, for example, the eel Kv1.1 S4-S5 region was
      identical to Kv1.5 and Kv1.6. Northern blot analysis indicated that eel Kv1.1
      mRNA was expressed at appreciable levels in the electric organ but it was not
      detected in eel brain, muscle, or cardiac tissue. Because electrocytes do not
      express robust outward voltage-gated potassium currents we speculate that eel
      Kv1.1 channels are chronically inhibited in the electric organ and may be
      functionally recruited by an unknown mechanism.

PMID- 14724752
TI  - Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice:
      implications for cholesterol gallstone formation.
AB  - C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been
      utilized for quantitative trait loci (QTL) analysis to identify the Lith 1 locus
      for cholelithiasis. Abcb11 encodes for the liver canalicular membrane bile salt
      export pump (BSEP), which maps to this QTL and is a candidate gene for Lith 1. We
      investigated the transmembrane transport of taurocholate in canalicular liver
      membrane vesicles isolated from these murine strains. Canalicular liver plasma
      membranes (cLPM) and RNA were isolated from C57L/J and AKR/J mice livers, and
      were utilized for Northern and Western blot analysis and functional (3)H
      taurocholate uptake studies. ATP-dependent (3)H-taurocholate uptake was
      significantly higher in AKR/J, compared to C57L/J mice. V(max) was 127 vs. 42
      pmol TC/mg/s in the murine strains, respectively, while K(m) was unchanged. In
      contrast, gene and protein expression of hepatic Abcb11 was increased three-fold
      in C57L/J, compared to AKR/J mice. Thus, Abcb11 bile salt transport activity per
      unit protein was reduced nine-fold in the C57L/J, compared to AKR/J mice. In
      contrast, canalicular membrane cholesterol:phospholipid content was also
      significantly higher in the C57L/J mice. We conclude that gallstone-susceptible
      C57L/J mice demonstrate increased gene and canalicular membrane expression of
      Abcb11, however, taurocholate transport is functionally diminished. The latter
      may be due to the increased cholesterol membrane content of the cLPM in C57L/J
      mice. These findings may be important for the pathogenesis of gallstone
      formation.

PMID- 14724754
TI  - The Ca(2+)-ATPase of the scallop sarcoplasmic reticulum is of a cold-adapted
      type.
AB  - At 0 to 20 degrees C, the Ca(2+)-ATPase activity of the scallop sarcoplasmic
      reticulum (SR) was observed to be 7-60% of the peak activity at 30 degrees C,
      while the ATPase activity of the rabbit SR was 0-7% of its peak at 55 degrees C.
      The relative rabbit ATPase activity (0.7-7.0%) at 7-20 degrees C became higher (6
      15 times) and lower (1/4-1/2), respectively, by the solubilization of the rabbit
      ATPase with a detergent, dodecyloctaethylenglycol monoether, and by the
      reconstitution of the ATPase with asolectin (soybean lecithin). No activity at 0
      degrees C remained irrespective of these treatments. The relative scallop ATPase
      activity at 0-20 degrees C was, however, scarcely affected by such solubilization
      and reconstitution. In contrast to the rabbit ATPase, the scallop ATPase seems to
      be capable of operating independently without the help of the membrane lipid at
      low temperature.

PMID- 14724753
TI  - Modulation of calcium-dependent chloride secretion by basolateral SK4-like
      channels in a human bronchial cell line.
AB  - The human bronchial cell line16HBE14o- was used as a model of airway epithelial
      cells to study the Ca(2+)-dependent Cl(-) secretion and the identity of K(Ca)
      channels involved in the generation of a favorable driving force for Cl(-) exit.
      After ionomycin application, a calcium-activated short-circuit current ( I(sc))
      developed, presenting a transient peak followed by a plateau phase. Both phases
      were inhibited to different degrees by NFA, glybenclamide and NPPB but DIDS was
      only effective on the peak phase. (86)Rb effluxes through both apical and
      basolateral membranes were stimulated by calcium, blocked by charybdotoxin,
      clotrimazole and TPA. 1-EBIO, a SK-channel opener, stimulated (86)Rb effluxes.
      Block of basolateral K(Ca) channels resulted in I(sc) inhibition but, while
      reduced, I(sc) was still observed if mucosal Cl(-) was lowered. Among SK family
      members, only SK4 and SK1 mRNAs were detected by RT-PCR. KCNQ1 mRNAs were also
      identified, but involvement of K(cAMP) channels in Cl(-) secretion was unlikely,
      since cAMP application had no effect on (86)Rb effluxes. Moreover, chromanol 293B
      or clofilium, specific inhibitors of KCNQ1 channels, had no effect on cAMP
      dependent I(sc). In conclusion, two distinct components of Cl(-) secretion were
      identified by a pharmacological approach after a Cai2+ rise. K(Ca) channels
      presenting the pharmacology of SK4 channels are present on both apical and
      basolateral membranes, but it is the basolateral SK4-like channels that play a
      major role in calcium-dependent chloride secretion in 16HBE14o- cells.

PMID- 14724755
TI  - Modulation of rabbit corneal epithelial cell proliferation by growth factor
      regulated K(+) channel activity.
AB  - We characterized the dependence of the mitogenic response by rabbit corneal
      epithelial (RCE) cells to serum containing growth factors on K(+) channel
      activation. Using both cell-attached and nystatin-perforated patch-clamp
      configurations, a K(+) channel was identified whose current-voltage relationship
      is linear with a single-channel conductance of 31 pS. Its activity was barely
      detectable following 24 h serum starvation. Exposure of starved cells to either
      10% FBS, 5 ng/ml epidermal growth factor (EGF) or 2 n M endothelin-1 (ET-1)
      continuously increased its activity within 30 min by 40%, 54% and 29%,
      respectively. EGF and ET-1 in combination had additive effects on such activity.
      Application of 100 micro M 4-aminopyridine (4-AP), a K(+) channel blocker,
      inhibited serum-stimulated K(+) channel activity by 85%. DNA synthesis was
      markedly stimulated by serum, whereas incubation with either 4-AP (200 micro M)
      or Ba(2+) (1 m M) suppressed this increase by 51% and 23%, respectively, whereas
      5 m M tetra ethyl ammonium (TEA) had no effect. Taken together, growth factor
      induced increases in proliferation are dependent on K(+) channel stimulation. As
      the increases in K(+) channel activity induced by ET-1 and EGF were additive,
      these mitogens may stimulate K(+) channel activity through different signaling
      pathways linked to their cognate receptors.

PMID- 14724756
TI  - Analysis of the properties of Bacillus thuringiensis insecticidal toxins using a
      potential-sensitive fluorescent probe.
AB  - A potential-sensitive fluorescent probe, 3,3'-dipropylthiadicarbocyanine iodide,
      was used to analyze, at pH 7.5 and 10.5, the effects of Bacillus thuringiensis
      toxins on the membrane potential generated by the efflux of K(+) ions from brush
      border membrane vesicles purified from the midgut of the tobacco hornworm,
      Manduca sexta. Fluorescence levels were strongly influenced by the pH and ionic
      strength of the media. Therefore, characterization of the effects of the toxins
      was conducted at constant pH and ionic strength. Under these conditions, the
      toxins had little effect on the fluorescence levels measured in the presence or
      absence of ionic gradients, indicating that the ionic selectivity of their pores
      is similar to that of the intact membrane. Valinomycin greatly increased the
      potential generated by the diffusion of K(+) ions although membrane permeability
      to the other ions used to maintain the ionic strength constant also influenced
      fluorescence levels. In the presence of valinomycin, active toxins (Cry1Aa,
      Cry1Ab, Cry1Ac, Cry1C and Cry1E) efficiently depolarized the membrane at pH 7.5
      and 10.5.

PMID- 14724757
TI  - Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various
      tissues in rats.
AB  - ATP-sensitive K(+) channels (K(ATP)) couple the intermediary metabolism to
      cellular excitability and play an important role in the cardio-protective effect
      of ischemic preconditioning and the activity-dependent autoregulation of cerebral
      circulation. Although previous studies using PCR and Northern blot suggest that
      the vascular isoform may consist of Kir6.1 and SUR2B, their expression and
      precise distribution in various vasculatures remain unknown. To illustrate their
      vascular expression, we performed this study using in situ hybridization
      histochemistry. Antisense riboprobes were synthesized by in vitro transcription
      and labeled with digoxigenin. Distributions of these mRNAs in the various blood
      vessels were revealed under a bright-field microscope. The expression of Kir6.1
      and SUR2B mRNAs was observed in small and intermediate arteries as well as
      arterioles in several tissues, including basilar, vertebral, mesenteric, coronary
      and renal arteries. The transcripts were found in arterial smooth muscles. Also,
      we observed Kir6.1/SUR2B expression in capillary beds. The Kir6.1 and SUR2B
      expression pattern showed clear overlap, suggesting that they may form
      heteromeric K(ATP) channels in these tissues. The Kir6.1 and SUR2B stains were
      detected in aorta and renal tubular cells although their expression level was
      extremely low. In contrast, the Kir6.1 and SUR2B mRNAs were not seen in vena
      cava, other small veins, myocardium and skeletal muscles. With their strong
      expression in small arteries and capillaries, it is very likely that the Kir6.1
      and SUR2B form the vascular isoform of K(ATP) channels in these vasculatures.

PMID- 14724758
TI  - Downregulation of the Na(+)- D-glucose cotransporter SGLT1 by protein RS1
      (RSC1A1) is dependent on dynamin and protein kinase C.
AB  - We have previously shown that the regulatory protein RS1, cloned from pig, rabbit
      and human (RSC1A1), is localized intracellularly and inhibits the transcription
      of the Na(+)- D-glucose cotransporter SGLT1 in LLC-PK(1) cells. We also reported
      that transport activities of human SGLT1 (hSGLT1) and human organic cation
      transporter hOCT2 expressed in Xenopus oocytes were decreased upon co-expression
      of human RS1 (hRS1). The present paper indicates that the glucose transporter
      GLUT1 and the peptide transporter PEPT1 are not influenced by hRS1. Voltage-clamp
      experiments in oocytes expressing hSGLT1 demonstrated that hRS1 reduced the
      maximal substrate-induced currents but did not change substrate activation,
      membrane potential dependence, Na(+) dependence or substrate selectivity of
      hSGLT1. Co-expression experiments with a dominant-negative dynamin mutant showed
      that the posttranslational inhibition of hSGLT1 by hRS1 was dependent on the
      function of dynamin. Finally, we observed that hRS1 changed the short-term effect
      of protein kinase C (PKC) on hSGLT1. Whereas the PKC activators phorbol-12
      myristate-13-acetate (PMA) and sn-1,2-dioctanoyl glycerol (DOG) increased alpha
      methyl glucose (AMG) uptake expressed by hSGLT1 alone as described earlier, PMA
      and DOG decreased AMG uptake mediated by hSGLT1 when hRS1 was co-expressed. Taken
      together, these data indicate that hRS1 modulates dynamin-dependent trafficking
      of intracellular vesicles containing hSGLT1 in Xenopus oocytes, and modulates PKC
      dependent short-term regulation of this transporter.

PMID- 14724759
TI  - Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+
      channels in rat palaeocortical neurons.
AB  - The effects of three divalent metal cations (Mn2+, Co2+, and Cu2+) on high
      voltage-activated (HVA) Ca2+ currents were studied in acutely dissociated
      pyramidal neurons of rat piriform cortex using the patch-clamp technique. Cu2+,
      Mn2+, and Co2+ blocked HVA currents conducted by Ba2+ ( IBa) with IC50 of
      approximately 920 nM, approximately 58 micro M, and approximately 65 micro M,
      respectively. Additionally, after application of non-saturating concentrations of
      the three cations, residual currents activated with substantially slower kinetics
      than control IBa. As a consequence, the current fraction abolished by the
      blocking cations typically displayed, in its early phase, an unusually fast
      decaying transient. The latter phenomenon turned out to be a subtraction
      artifact, since none of the pharmacological components (L-, N-, P/Q-, and R-type)
      that constitute the total HVA currents under study showed a similarly fast early
      decay: hence, the slow activation kinetics of residual currents was not due to
      the preferential inhibition of a fast-activating/inactivating component, but
      rather to a true slowing effect of the blocker cations. The percent IBa-amplitude
      inhibition caused by Mn2+, Co2+, and Cu2+ was voltage-independent over the whole
      potential range explored (up to +30 mV), hence the slowing of IBa activation
      kinetics was not due to a mechanism of voltage- and time-dependent relief from
      block. Moreover, Mn2+, Co2+, and Cu2+ significantly reduced I(Ba) deactivation
      speed upon repolarization, which also is not compatible with a depolarization
      dependent unblocking mechanism. The above results show that 1) Cu2+ is a
      particularly potent HVA Ca2+-channel blocker in rat palaeocortical neurons; and
      2) Mn2+, Co2+, and Cu2+, besides exerting a blocking action on HVA Ca2+-channels,
      also modify Ca2+-current activation and deactivation kinetics, most probably by
      directly interfering with channel-state transitions.

PMID- 14724760
TI  - Electrostatic influence on ion transport through the alphaHL channel.
AB  - The current-voltage relationship of a single Staphylococcus aureus alpha
      hemolysin (alphaHL) channel is nonlinear, rectifying, and depends on the bulk pH
      and the ionic strength. The data are described qualitatively by a simple one
      dimensional Nernst-Planck analysis in which the fixed charges inside and near the
      pore's entrances affect the transport of ions through the channel. The distances
      of these fixed charges from one of the channel's entrances are obtained from the
      channel's crystal structure. The model demonstrates that rectification of
      monovalent ion flow through the alphaHL channel can be related to the asymmetry
      in the location of the ionizable amino acid side chains.

PMID- 14724761
TI  - Modulation of native TREK-1 and Kv1.4 K+ channels by polyunsaturated fatty acids
      and lysophospholipids.
AB  - The modulation of TREK-1 leak and Kv1.4 voltage-gated K+ channels by fatty acids
      and lysophospholipids was studied in bovine adrenal zona fasciculata (AZF) cells.
      In whole-cell patch-clamp recordings, arachidonic acid (AA) (1-20 microM)
      dramatically and reversibly increased the activity of bTREK-1, while inhibiting
      bKv1.4 current by mechanisms that occurred with distinctly different kinetics.
      bTREK-1 was also activated by the polyunsaturated cis fatty acid linoleic acid
      but not by the trans polyunsaturated fatty acid linolelaidic acid or saturated
      fatty acids. Eicosatetraynoic acid (ETYA), which blocks formation of active AA
      metabolites, failed to inhibit AA activation of bTREK-1, indicating that AA acts
      directly. Compared to activation of bTREK-1, inhibition of bKv1.4 by AA was rapid
      and accompanied by a pronounced acceleration of inactivation kinetics. Cis
      polyunsaturated fatty acids were much more effective than trans or saturated
      fatty acids at inhibiting bKv1.4. ETYA also effectively inhibited bKv1.4, but
      less potently than AA. bTREK-1 current was markedly increased by
      lysophospholipids including lysophosphatidyl choline (LPC) and lysophosphatidyl
      inositol (LPI). At concentrations from 1-5 microM, LPC produced a rapid,
      transient increase in bTREK-1 that peaked within one minute and then rapidly
      desensitized. The transient lysophospholipid-induced increases in bTREK-1 did not
      require the presence of ATP or GTP in the pipette solution. These results
      indicate that the activity of native leak and voltage-gated K+ channels are
      directly modulated in reciprocal fashion by AA and other cis unsaturated fatty
      acids. They also show that lysophospholipids enhance bTREK-1, but with a
      strikingly different temporal pattern. The modulation of native K+ channels by
      these agents differs from their effects on the same channels expressed in
      heterologous cells, highlighting the critical importance of auxiliary subunits
      and signaling. Finally, these results reveal that AZF cells express thousands of
      bTREK-1 K+ channels that lie dormant until activated by metabolites including
      phospholipase A2 (PLA2)-generated fatty acids and lysophospholipids. These
      metabolites may alter the electrical and secretory properties of AZF cells by
      modulating bTREK-1 and bKv1.4 K+ channels.

PMID- 14724762
TI  - The kinetics of non-lamellar phase formation in DOPE-Me: relevance to biomembrane
      fusion.
AB  - The mechanism of the lamellar/inverted cubic (QII) phase transition is related to
      that of membrane fusion in lipid systems. N-Monomethylated
      dioleoylphosphatidylethanolamine (DOPE-Me) exhibits this transition and is
      commonly used to investigate the effects of exogenous substances, such as viral
      fusion peptides, on the mechanism of membrane fusion. We studied DOPE-Me phase
      behavior as a first step in evaluating the effects of membrane-spanning peptides
      on inverted phase formation and membrane fusion. These measurements show that: a)
      the onset temperatures for QII and inverted hexagonal (HII) phase formation both
      are temperature scan rate-dependent; b) longer pre-incubation times at low
      temperature and lower temperature scan rates favor formation of the QII phase;
      and c) in temperature-jump experiments between 61 and 65 degrees C, the meta
      stable HII phase forms initially, and disappears slowly while the QII phase
      develops. These observations are rationalized in the context of a mechanism for
      both the lamellar/non-lamellar phase transition and the related process of
      membrane fusion.

PMID- 14724763
TI  - Activation of apical K+ conductances by muscarinic receptor stimulation in rat
      distal colon: fast and slow components.
AB  - In the epithelium of rat distal colon the acetylcholine analogue carbachol
      induces a transient increase of short-circuit current (Isc) via stimulation of
      cellular K+ conductances. Inhibition of the turnover of inositol-1,4,5
      trisphosphate (IP3) by LiCl significantly reduced both the amplitude and the
      duration of this response. When the apical membrane was permeabilized with
      nystatin, LiCl nearly abolished the carbachol-induced activation of basolateral
      K+ conductances. In contrast, in epithelia, in which the basolateral membrane was
      bypassed by a basolateral depolarization, carbachol induced a biphasic increase
      in the K+ current across the apical membrane consisting of an early component
      carried by charybdotoxin- and tetraethylammonium-sensitive K+ channels followed
      by a sustained plateau carried by channels insensitive against these blockers.
      Only the latter was sensitive against LiCl or inhibition of protein kinases. In
      contrast, the stimulation of the early apical K+ conductance by carbachol proved
      to be resistant against inhibition of phospholipase C or protein kinases.
      However, apical dichlorobenzamil, an inhibitor of Na+/Ca2+ exchangers, or a Ca2+
      free mucosal buffer solution significantly reduced the early component of the
      carbachol-induced apical K+ current. The presence of an apically localized
      Na+/Ca2+-exchanger was proven immunohistochemically. Taken together these
      experiments reveal divergent regulatory mechanisms for the stimulation of apical
      Ca2+-dependent K+ channels in this secretory epithelium, part of them being
      activated by an inflow of Ca2+ across the apical membrane.

PMID- 14724766
TI  - Pediatric gynecology: assessment strategies and common problems.
AB  - Pediatric gynecology is an emerging subspecialty involving the collaborative
      efforts of health professionals from gynecology, pediatrics, and urology. The
      gynecologic problems encountered in the pediatric population are unique to this
      age group and involve physician skills differing from those utilized with an
      adult population. The purpose of this manuscript is to describe the normal
      anatomy and physiology of the reproductive tract and genitalia and common
      problems seen in the prepubertal female. Common anatomic variations are
      considered. Suggestions on assessment techniques for evaluation of the young
      child are discussed. Presentation of common gynecologic problems in the
      prepubertal child will include common symptoms, evaluation and testing, and
      management to enable the practicing gynecology health professional to provide
      compassionate and quality care to the young female.

PMID- 14724767
TI  - Disorders of pubertal development: precocious puberty.
AB  - Puberty is a complex developmental process culminating in sexual maturity. This
      transitional period begins in late childhood and is characterized by maturation
      of the hypothalamic-pituitary-gonadal axis, the appearance of secondary sexual
      characteristics, acceleration of growth, and, ultimately, the capacity for
      fertility. Significant endocrinologic changes accompany these developmental
      events. Disorders of pubertal development may occur at any of the steps of the
      maturational process leading to either precocious or delayed puberty. A thorough
      understanding of the normal pubertal process is important to the accurate
      diagnosis and treatment of pubertal disorders.

PMID- 14724768
TI  - Delayed puberty and amenorrhea.
AB  - The ability to diagnose and manage disorders that cause delayed puberty requires
      a thorough understanding of the physical and hormonal events of puberty. Wide
      variation exists within normal pubertal maturation, but most adolescent girls in
      the United States have begun to mature by the age of 13. Delayed puberty, a rare
      condition in girls, occurs in only approximately 2.5% of the population.
      Constitutional delay, genetic defects, or hypothalamic-pituitary disorders are
      common causes. Amenorrhea, often found as a symptom of delayed puberty, may be
      due to congenital genital tract anomalies, ovarian failure, or chronic
      anovulation with estrogen presence or with estrogen absence.

PMID- 14724769
TI  - Abnormal bleeding in adolescents.
AB  - Abnormal bleeding is a common clinical problem in adolescents, with the vast
      majority of cases resulting from anovulatory menstrual cycles. Although most
      episodes of abnormal vaginal bleeding do not cause acute medical complications,
      bleeding can be traumatic for young patients and their families. Health care
      providers with a solid knowledge of menstrual physiology and a thorough approach
      to differential diagnosis can evaluate and appropriately manage adolescents. In
      this article, we review the maturation of the hypothalamic ovarian axis, the most
      frequent etiologies of abnormal bleeding, as well as other less common causes and
      discuss diagnosis and treatment modalities.

PMID- 14724770
TI  - Mullerian anomalies.
AB  - The reproductive organs in both males and females consist of gonads, internal
      ductal structures, and external genitalia. Normal sexual differentiation is
      dependent on the genetic sex determined by the presence or absence of the Y
      chromosome at fertilization. Testes develop under the influence of the Y
      chromosome and ovaries develop when no Y chromosome is present. In the absence of
      testes and their normal hormonal products, sexual differentiation proceeds along
      the female pathway, resulting in a normal female phenotype. Anatomic gynecologic
      anomalies occur when there is failure of normal embryologic ductal development.
      These anomalies include congenital absence of the vagina as well as defects in
      lateral and vertical fusion of the Mullerian ducts. Treatment of mullerian
      anomalies begins with the correct identification of the anomaly and an
      understanding of the embryologic origin. This includes evaluation for other
      associated anomalies such as renal or skeletal abnormalities. After correct
      identification, treatment options include nonsurgical as well as surgical
      intervention. This chapter serves to review the embryology and development of the
      reproductive system and to describe common genital tract anomalies. Details of
      surgical or nonsurgical correction of these anomalies are presented.

PMID- 14724771
TI  - Contraceptive choices in medically ill adolescents.
AB  - More than 50% of all women in the United States have had sexual intercourse by 18
      years of age. Up to one half of these adolescents do not use contraception at
      first intercourse. Although chronically ill adolescents may differ slightly from
      these norms, such differences are probably minor. Prevention of adolescent
      pregnancy remains a challenge in the medical community, and this can be
      especially difficult for the chronically ill adolescent. In some cases,
      medications taken for certain chronic conditions may alter the effectiveness of
      hormonal contraception, and pregnancy in these cases may pose substantial risks
      to the mother as well as her fetus.

PMID- 14724772
TI  - Sexually transmitted diseases.
AB  - Sexually transmitted diseases (STDs) constitute a major health burden in the
      United States, causing pelvic inflammatory disease, ectopic pregnancy,
      infertility, chronic pelvic pain, genital lesions, genital neoplasms, adverse
      pregnancy outcomes, immune system dysfunction, liver disease, and even death.
      STDs disproportionately affect adolescents and young adults. Of the estimated 15
      million STDs that occur annually each year in the United States, 4 million are
      among adolescents and 6 million among young adults. The current epidemic is
      complicated by the high asymptomatic carrier state associated with most STDs and
      the inadequate protection of condoms in preventing transmission. Sexually active
      individuals, particularly adolescents, must be educated on the ramifications of
      early onset of sexual activity and the health consequences of multiple sexual
      partners.

PMID- 14724773
TI  - [Erectile dysfunction. Are interdisciplinary diagnosis and therapy necessary?].
AB  - OBJECTIVE: The last few decades have seen a marked increase in mean life
      expectancy in Central Europe. This has made elderly people and their quality of
      life a matter of ever-increasing medical concern. Besides the lack of population
      based studies in Central Europe, the identifying risk factors for the development
      of erectile dysfunction (ED) is crucial. METHODS AND MATERIAL: A newly developed
      and validated questionnaire on male erectile dysfunction was mailed to a
      representative population sample of 8000 men 30 to 80 years of age in the Cologne
      urban district. RESULTS: The response included 4489 analysable replies (56,1 %).
      The median age was 51,8 years. Prevalence of ED was estimated at about 19.2 %,
      with a steep age-related increase (2,3 - 53,4 %) Therapeutic necessity (defined
      by co-occurrence of ED and dissatisfaction with sex life), also increases with
      age. The overall number of ED sufferers seeking therapy was 6,8 %. The following
      illnesses where seen in the ED group: heart failure (14,7 %), pelvic surgery
      (18,8 %), diabetes mellitus (20,2 %), peripheral arterial circulatory disorders
      (21,5 %), herniated disc (23,2 %) and hypertension (32,0 %). Although the
      pathogenetic pathway remains unclear with a prevalence of 72 % "lower urinary
      tract symptoms" (LUTS) seems to be an age independent risk factor. In contrast,
      the prevalence of ED in healthy men was around 6,6 %. CONCLUSIONS: ED is a common
      disorder, contributing to dissatisfaction with sex life in a considerable
      proportion of men. ED is frequently associated with chronic diseases. For this
      reason adequate interdisciplinary diagnostic workup is essential, to offer
      patients individually adapted treatment.

PMID- 14724774
TI  - [The development of a toxic megacolon due to Amanita phalloides poisoning. A rare
      complication].
AB  - HISTORY: A 71-year-old previously healthy man consumed a mushroom meal containing
      Amanita phalloides, which he had confused with Agaricus campestris. Approximately
      8 hours later, typical gastrointestinal symptoms began with copious loss of
      fluids. Treatment with penicillin G was initiated followed by a continuous
      silibinin infusion before the patient was transferred to our toxicological
      department. Other than a transient tachycardia and diffuse pain on abdominal
      palpation clinical examination was without abnormal findings. INVESTIGATIONS:
      Laboratory findings showed severe hepatic damage with 100-fold increased
      transaminases, elevation of serum creatinine, hyperbilirubinemia and a serious
      disturbance of coagulation. Infection with HIV, hepatitis- and CMV as well as
      pathogenic enteric bacteria and antibiotic-associated pseudo-membranous colitis
      were excluded. 11 days after the mushroom meal x-ray of abdomen showed a 6 cm
      dilatation of the small intestine and an 8 cm dilatation of the colon. DIAGNOSIS
      AND TREATMENT: Although clinical condition and laboratory findings nearly
      fulfilled transplantation criteria, hepatic injury resolved during intensive care
      therapy. Intractable diarrhea, dilatation of the intestine on x-ray as well as
      other findings met criteria of toxic megacolon. Therapy with antibiotics and
      systemic steroids was ineffective, so the patient needed decompression by a
      catheter, which was placed by colonoscopy. 30 days after the serious amanita
      poisoning complicated by development of toxic megacolon, the patient's condition
      resolved without sequelae and he was discharged. CONCLUSIONS: In addition the
      well known complications of amanita-poisoning, such as hepatic failure,
      encephalopathy and multi-organ failure, involvement of other organs like bone
      marrow, pancreas, kidney and gastrointestinal tract (except for the initial
      cholera-like gastroenteritis) are not well documented in the literature. Uncommon
      complications like toxic megacolon require an empirical approach.

PMID- 14724775
TI  - [Vitamin B6-sensitive hereditary sideroblastic anemia].
AB  - HISTORY: A 30-year-old patient was admitted for investigation of microcytotic,
      hypochromic anemia (hemoglobin 8.3 g/dl) with splenomegaly. INVESTIGATIONS: Bone
      marrow smear showed a normocellular marrow with augmented severely dysplastic
      erythropoesis. Prussian-blue staining revealed an increased number of ring
      sideroblasts, thus myelodysplastic syndrome (refractory anemia with
      ringsideroblasts) was suspected. DIAGNOSIS AND TREATMENT: Review of former
      laboratory values and investigations of the patient's family revealed the correct
      diagnosis of x-linked sideroblastic anemia (XLSA). The patient was treated with
      oral pyridoxine. Hemoglobin levels steadily increased, so the diagnosis of
      pyridoxine-responsive sideroblastic anemia was made. Liver biopsy showed
      secondary fibrosis with beginning cirrhosis due to iron overload. Therapy with
      deferoxamine and phlebotomies was initiated. CONCLUSION: XLSA is a rare
      differential diagnosis of acquired forms of sideroblastic anemias. A high degree
      of clinical suspicion is necessary for diagnosis because morphological studies
      such as histology and cytology may not yield conclusive results. A correct
      diagnosis is especially important because of the uncomplicated therapeutic
      options.

PMID- 14724776
TI  - [Evaluation and follow-up of living kidney donors].
AB  - An increase in waiting time for a cadaveric organs and a better graft-function,
      graft- and patient-survival with kidneys from a living donors have lead to an
      increase in living-donor renal transplantation in the therapy of end-stage renal
      disease. In Germany, with the implementation of a transplantation law in 1997 and
      due to improved surgical techniques (laparoscopy) the proportion of living renal
      donors has almost tripled during the last five years. The transplantation law
      also names the potential donors, including not only genetically related but also
      emotionally related donors. Inclusion criteria for living donation are age > 18
      years, mental ability to give consent and an altruistic motivation (exclusion of
      financial benefits for the donor). If ABO blood group compatibility between donor
      and recipient is given and a cross match does not reveal immunologic obstacles a
      thorough medical and psychological examination must be performed with the
      potential donor. All risk factors for the donor beyond the actual operation must
      be excluded. Therefore all organ-systems have to be evaluated and risks for the
      donor as well as transferable pathologies and infections must be ruled out.
      International guidelines help to perform an efficient evaluation. Following organ
      donation the donor should be medically controlled as requested by law. Also,
      psychological counselling should be offered. The aim is to minimize risks for the
      single kidney and to recognize early potentially kidney damaging affections.

PMID- 14724777
TI  - [Neurocardiological acute care].

PMID- 14724778
TI  - [Passive smoking--current position of science].
AB  - Among all indoor pollutants, environmental tobacco smoke (ETS) might be the most
      important. In population-based studies 30 to 60 % of the participants reported
      regular exposure to ETS. ETS has been classified as carcinogenic by several
      national and international agencies. In 2002, a paragraph on restriction of
      smoking at the workplace has been added to the German Workplaces Ordinance.
      International meta-analyses have been published on the potential health effects
      of ETS exposure. In these studies, the pooled relative risk (RR) for lung cancer
      has been estimated between 1.1 and 1.3. The pooled risk estimate for coronary
      heart disease (CHD) was slightly higher (1.25 - 1.35). The RR in the group with
      the highest exposure might be as high as 2. An increased risk has also be shown
      consistently for respiratory symptoms, asthma, and COPD. Because of the high
      incidence of CHD the public health impact of ETS exposure on CHD might be higher
      than the impact due to additional lung cancer cases.

PMID- 14724779
TI  - [Does the size of the birth clinic have an influence on neonatal survival?
      Evaluation of "avoidable" death cases in Hessen from 1990 to 2000. Article from
      DMW 13/2003].

PMID- 14724781
TI  - [Prospective study comparing conventional and transnasal
      esophagogastroduodenoscopy for routine diagnosis].
AB  - INTRODUCTION: Transnasal gastroscopy (TNG) is the result of ongoing improvements
      in endoscopic device development. These ultrathin endoscopes are planned to
      improve patient satisfaction with the endoscopic procedure. AIM: The aim of the
      current study was to prospectively evaluate the performance and patient
      acceptance of transnasal gastroscopy. PATIENTS AND METHODS: Sixty-three
      consecutive patients (40 males, 23 females, mean age 58.5 years) referred for
      routine upper gastrointestinal endoscopy to our tertiary care referral centre
      were assigned to one of three groups: first time transnasal gastroscopy (group 1,
      TNG), first time transoral gastroscopy (group 2, TOG) and transnasal gastroscopy
      after a previous unsedated transoral gastroscopy (group 3). All examinations were
      performed without intravenous sedation. Patients answered a standardised
      questionnaire immediately following the examination. RESULTS: The three groups of
      patients did not differ in age, gender or reason for gastroscopy. Investigations
      performed using transnasal technique were significantly shorter (TNG 8.9 min and
      9.2 min vs. TOG 11.9 min, p = 0.011 and p = 0.026, respectively) than those
      performed in transoral technique. Nosebleeding, albeit not clinically
      significant, and the urge to wretch were significantly more common in the
      transnasal technique group (p > 0.001). Patient acceptance tended to score higher
      in the transnasal technique groups, however not statistically higher. A greater
      number of patients from group 3 (TNG after previous TOG) would prefer a repeat
      exam via the transnasal route. CONCLUSIONS: Transnasal gastroscopy represents a
      possible alternative to the conventional transoral technique. TNG entails less
      subjective patient discomfort, and patients experienced in both techniques prefer
      the transnasal route. Shorter examination times and lack of intravenous sedation
      result in several benefits: no sedation-related complications, shorter post
      procedure observation times, and subsequently shorter time off work for patients.

PMID- 14724780
TI  - [Patient classification and analysis of risk profiles for type 2 diabetics as the
      main focus point in practice. Results of the TEMPO study].
AB  - BACKGROUND AND OBJECTIVE: Disease management programs (DMP) e. g. for diabetes
      mellitus, should be the clinical and economic basis for a structured treatment.
      This article shows results of specialized outpatient treatment using a risk
      factor depending patient classification. PATIENTS AND METHODS: Diabetes
      associated co-morbidities, micro- and macrovascular complications, the results
      and findings of blood pressure and metabolism of glucose and lipids, as well as
      all treatment-associated costs of 5245 type 2 diabetics were collected for a
      period of 12 months, accompanied by different measures of quality control. For
      documentation in the centres, all available original data were used as local data
      sources. RESULTS: The patient classification system, on which diabetic risk
      profiles are based, covered 74.3 % of all type 2 diabetic patients. Daily direct
      costs for all treatment measures ranged between EUR 4.79 (primary prevention) and
      EUR 8.96 for patients suffering from advanced diabetic foot syndrome. Most of the
      treatment costs arose from prescriptions of pharmaceuticals, other remedies and
      aids. Specific strategies of therapy were both related to the severity of co
      morbidities and the time since manifestation of diabetes (r = 0.486; p < 0.01,
      two-sided). The share of patients receiving diet and exercise only decreased from
      22.8 % (primary prevention) to below 10 % of patients suffering from
      microvascular complications. Simultaneously, the share of patients receiving
      insulin increased up to 81.8 % of patients suffering from advanced diabetic
      retinopathy. CONCLUSION: The risk profile specific variation in the results
      clearly shows the need of a risk factor depending classification system for type
      2 diabetes, which could be useful to reform and focus the system of compensating
      payments between health insurance companies more and more on morbidity, or on
      risk profiles.

PMID- 14724782
TI  - [Thrombus attached to a Sideris septal occluder system 6 years later].
AB  - HISTORY AND CLINICAL FINDINGS: A 61-year-old man was admitted to hospital because
      of right-sided hypaesthesia. Additionally he reported a brief speech disturbance
      some weeks before. Neurological examination indicated right-sided sensomotoric
      hemiparesis and left-sided upper quadrant anopia. 6 years ago recurrent transient
      ischaemic attacks (TIA) was diagnosed caused by paradoxical embolism through a
      persistent foramen ovale (PFO). The PFO was closed with a 45 mm Sideris button
      occluder device. After this, he reported no symptoms of cerebral ischaemia and he
      did not take any antiplatelet therapy. INVESTIGATIONS: Transesophageal
      echocardiography (TEE) showed a left atrial thrombus attached to the occluder.
      Cerebral computed tomography revealed infarction in regions supplied by the right
      posterior cerebral artery and left media cerebral artery. As additional risk
      factor for thrombosis a heterozygous factor V Leiden mutation was diagnosed.
      DIAGNOSIS: Multiple cerebral infarctions caused by a thrombus attached to an
      occluder system 6 years after interventional closure of persistent foramen ovale
      in a patient with heterozygous factor V Leiden mutation. TREATMENT AND COURSE:
      The patient was anticoagulated (phenprocoumon) and the thrombus gradually
      dissolved. CONCLUSION: A thrombosis on a Sideris occluder device may cause
      cerebral infarctions even years after transcatheter closure of a PFO.

PMID- 14724783
TI  - [Bioterrorism and the lungs].

PMID- 14724784
TI  - [Pulse wave reflection. Determination, extent of influence, analysis and use
      options].

PMID- 14724785
TI  - [How does technology influence medical transactions?].

PMID- 14724786
TI  - [Long-term study of the psychological effects in clinical rehabilitation (VESPER
      Study)].

PMID- 14724787
TI  - [Long-term study of the psychological effects of clinical rehabilitation (VESPER
      Study)].

PMID- 14724790
TI  - An unusual cause of refusal to walk.

PMID- 14724791
TI  - Molecular biology of the human immunodeficiency virus: current and future targets
      for intervention.
AB  - Inhibitors of the reverse transcriptase and protease enzymes of the human
      immunodeficiency virus form the backbone of current antiretroviral therapy.
      However, other therapeutic targets have been identified in studies of
      interactions between HIV and its target cells. This review presents an overview
      of HIV replication, emphasizing recently recognized cellular and viral molecules
      that may be exploited in future pharmacological approaches to prevent and treat
      infection with HIV.

PMID- 14724792
TI  - Principles of antiretroviral treatment of children and adolescents with human
      immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV) infection requires life-long therapy to attain
      durable suppression of HIV replication and prevent or reverse HIV-related
      symptoms or immune system dysfunction. Combination therapy with 3 or more
      antiretroviral medications is currently widely recommended for treatment of
      children and adolescents with HIV infection. While potent regimens can initially
      reduce virus load to below assay quantitation limits in the majority of persons
      with HIV infection, 30% to 80% of children will have regimen failure and return
      of detectable plasma virus within 1 year. Adherence to therapy is critical to
      regimen success. Optimal treatment requires careful use of potent combinations of
      drugs, with attention to adherence, palatability, toxicity, and pharmacokinetics.
      Practitioners with experience caring for children and adolescents with HIV
      infection should be involved.

PMID- 14724793
TI  - Pharmacology considerations for antiretroviral therapy in human immunodeficiency
      virus (HIV)-infected children.
AB  - The contemporary treatment of the child infected with human immunodeficiency
      virus (HIV) unavoidably requires combination therapy with antiretroviral agents
      and may include additional drugs for the prevention and treatment of
      opportunistic infections or other disease states. The current guidelines for the
      treatment of the HIV-infected child recommend that the same principles of
      treatment for adults should apply to children. However, the pharmacokinetic and
      pharmacodynamic characteristics of many agents and regimens used in adults have
      not been defined adequately in children, and large-scale clinical trials to
      establish safety and show efficacy have not been completed. Therefore, the
      clinician will be required to use agents with incomplete knowledge about their
      pharmacologic properties. The purpose of this article is to provide an overview
      of the pediatric pharmacologic principles, a review of the pharmacologic
      characteristics of selected antiretroviral agents in children, and a prospectus
      on the design of drug dosing regimens in children.

PMID- 14724794
TI  - Advances in the prevention of vertical transmission of human immunodeficiency
      virus.
AB  - The major mode of acquisition of human immunodeficiency virus (HIV) for children
      is through mother-to-child transmission, which can occur during pregnancy or
      labor and delivery, or postnatally through breastfeeding. In resource-rich
      countries, mother-to-child HIV transmission has decreased to less than 2 percent
      after recommendations for universal prenatal HIV counseling and testing,
      antiretroviral prophylaxis and elective cesarean delivery, and avoidance of
      breastfeeding were implemented. In resource-limited settings, effective, shorter,
      and less expensive antiretroviral prophylaxis interventions also have been
      identified, but implementation has been slower, and continued transmission
      through breastfeeding remains a significant problem. This review summarizes
      recent advances made in prevention of mother-to-child transmission of HIV in the
      United States and other resource-rich countries, as well as progress in resource
      limited countries.

PMID- 14724795
TI  - No greater gift than hope.

PMID- 14724796
TI  - Dr. Jonathan Mann: champion for human rights in the fight against AIDS.
AB  - On September 2, 1998, a Swissair jetliner headed to Geneva, Switzerland, crashed
      off the coast of Canada. Among the passengers on board were Jonathan Mann and his
      wife, both highly respected and renowned researchers who were headed to a United
      Nations AIDS vaccine conference. Jonathan Mann had held many high-level positions
      at the Centers for Disease Control and Prevention (CDC) before establishing the
      World Health Organization's (WHO's) Global Programme on AIDS, which he ran from
      1986 to 1990. This article presents a brief biography of Mann, with emphasis
      placed on his contributions to the progress that has been made in treating
      children with human immunodeficiency virus (HIV) and acquired immunodeficiency
      syndrome (AIDS), as well as on his efforts to protect individuals with AIDS and
      to establish appropriate attitudes toward them when the disease was still an
      emerging and frightening one that sparked controversy and fear.

PMID- 14724799
TI  - MDR1 gene polymorphism in ulcerative colitis.

PMID- 14724805
TI  - Redefining autoimmunity.

PMID- 14724804
TI  - This month at the NIH: NIH roadmap: accelerating medical discovery to improve
      health.

PMID- 14724806
TI  - Image of the month. Esophageal foreign body.

PMID- 14724807
TI  - Survival and cause-specific mortality in ulcerative colitis: follow-up of a
      population-based cohort in Copenhagen County.
AB  - BACKGROUND & AIMS: A population-based cohort from Copenhagen County comprising
      1160 patients diagnosed with ulcerative colitis between 1962 and 1987 was
      followed-up until 1997 to describe survival and cause-specific mortality.
      METHODS: Observed vs. expected deaths were presented as standardized mortality
      ratio (SMR) with exact 95% confidence intervals (CI) calculated by using
      individually registered person-years at risk and Danish 1995 mortality rates.
      Cumulative survival curves were calculated. RESULTS: A total of 261 deaths
      occurred, not significantly different from the expected number of 249 (SMR, 1.05;
      95% CI, 0.92-1.19). The median age at death among men was 70 years (range, 6-96
      years) and among women 74 years (range, 25-96 years). Twenty-five deaths (9.6%)
      were caused by complications to ulcerative colitis, mostly infectious and
      cardiovascular postoperative complications. Patients older than 50 years of age
      at diagnosis and with extensive colitis showed an increased mortality within the
      first 2 years because of ulcerative colitis-associated causes. The mortality from
      colorectal cancer was not increased and that of cancer in general was
      significantly lower than expected: 50 vs. 71 (SMR, 0.70; 95% CI, 0.52-0.93). A
      significantly increased mortality from pulmonary embolism and pneumonia was
      found. Among women only, death from genitourinary tract diseases and suicide was
      significantly increased. CONCLUSIONS: Despite an overall normal life expectancy
      for patients with ulcerative colitis, patients >50 years of age and with
      extensive colitis at diagnosis had increased mortality within the first 2 years
      after diagnosis, owing to colitis-associated postoperative complications and
      comorbidity.

PMID- 14724808
TI  - Mortality in inflammatory bowel disease: a population-based cohort study.
AB  - BACKGROUND & AIMS: There is no consensus regarding any increase in mortality with
      inflammatory bowel disease (IBD). In general, previous studies were not
      contemporary and were unable to correct for likely confounders. We have performed
      a large cohort study to examine contemporary IBD related mortality in the United
      Kingdom. METHODS: We selected subjects within the General Practice Research
      Database with a coded diagnosis of inflammatory bowel disease and up to 5 matched
      controls for each. We derived the date of recorded deaths and information on
      smoking and a variety of medical conditions. We calculated both the absolute risk
      of death and the relative risk as a hazard ratio corrected for available
      confounders by Cox regression. RESULTS: We included 16,550 IBD cases with 1047
      deaths and 82,917 controls with 3758 deaths. The mortality rate was 17.1 per 1000
      person-years overall for IBD cases and 12.3 for controls; this difference was
      greatest in the elderly. Conversion of these figures to hazard ratios by Cox
      regression gave hazard ratios of 1.54 (1.44-1.65) for all IBD, 1.44 (1.31-1.58)
      for ulcerative colitis (UC), and 1.73 (1.54-1.96) for Crohn's disease. The
      greatest hazard ratio for UC was among the 40-59-year age group (1.79 [1.42
      2.27]) and for Crohn's disease among 20-39-year-olds (3.82 [2.17-6.75]).
      CONCLUSIONS: IBD is associated with an overall small increase in mortality rate
      greatest in relative terms in younger subjects but in absolute terms in the
      elderly.

PMID- 14724809
TI  - Doppler of the Doppler ultrasound effect.

PMID- 14724810
TI  - Inflammatory bowel disease and the risk of fracture.
AB  - BACKGROUND & AIMS: Although patients with inflammatory bowel disease (IBD) have
      reduced bone mass, there is controversy whether there is an increased risk of
      fracture. This study examines the risk of fracture and its predictors in patients
      with IBD. METHODS: In a primary care- based nested case-control study, 231,778
      fracture cases and 231,778 age- and sex-matched controls were recruited. A
      history of IBD was assessed from medical records. RESULTS: The prevalence of IBD
      was 156 and 282 per 100,000 for Crohn's disease (CD) and ulcerative colitis (UC),
      respectively. Patients with IBD had an increased risk of vertebral fracture (odds
      ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.61) and hip fracture (OR,
      1.59; 95% CI, 1.14-2.23). The risk of hip fracture was greater in patients with
      CD (OR, 1.86; 95% CI, 1.08-3.21) compared with UC (OR, 1.40; 95% CI, 0.92-2.13).
      Disease severity, assessed by the number of symptoms, predicted fracture even
      after adjusting for corticosteroid use (OR, 1.46; 95% CI, 1.04-2.04). Only 13% of
      patients with IBD who had already sustained a fracture were on any form of
      antifracture treatment. CONCLUSIONS: Patients with IBD have a higher risk of
      fracture due to both disease activity and use of oral corticosteroids. However,
      few of these patients are receiving optimal bone-sparing therapy, highlighting
      the importance of increasing awareness of osteoporosis in those managing these
      patients.

PMID- 14724811
TI  - Subclinical intestinal inflammation and sacroiliac changes in relatives of
      patients with ankylosing spondylitis.
AB  - BACKGROUND & AIMS: It has been suggested that subclinical intestinal inflammation
      plays a pathogenic role in the spondylarthropathy of ankylosing spondylitis (AS).
      We assessed the possible presence and inheritance pattern of subclinical
      intestinal inflammation in first-degree relatives of patients with AS. The
      relationship between this inflammation and the subjects' HLA-B27 genotype as well
      as computerized tomographic sacroiliac abnormalities was also assessed. METHODS:
      A total of 124 of 213 (58%) available first-degree relatives of 47 patients with
      AS in Iceland underwent investigation for intestinal inflammation (fecal
      calprotectin concentration), HLA-B27 genotyping, and computerized tomography of
      the sacroiliac joints. RESULTS: A total of 41% of the first-degree relatives had
      subclinical intestinal inflammation, whereas 15 of 17 spouses were normal.
      Variance components analyses suggest that the inheritance pattern of this
      inflammation is affected by a major additive gene. Some sacroiliac changes,
      suggestive of early AS, differed significantly between subjects with and without
      subclinical intestinal inflammation (mean diameter of subchondral cysts [2.9 vs.
      1.2 mm; P = 0.026] and blurring of joint margins [9 of 44 (20%) vs. 1 of 41 (2%);
      P = 0.02]). Intestinal inflammation and sacroiliac changes did not relate to the
      subjects' HLA-B27 status. CONCLUSIONS: Many first-degree relatives of patients
      with AS appear to have an inherited abnormality that leads to subclinical
      intestinal inflammation. The association between the presence of this
      inflammation and the sacroiliac changes suggests that it may play a pathogenic
      role in the spondylarthropathy of AS.

PMID- 14724812
TI  - Unsedated ultrathin EGD is well accepted when compared with conventional sedated
      EGD: a multicenter randomized trial.
AB  - BACKGROUND & AIMS: In the United States, upper gastrointestinal endoscopy is
      usually performed using intravenous sedation. Sedation increases the rate of both
      complications and costs of endoscopy. Unsedated esophagogastroduodenoscopy (EGD)
      using conventional 8-11-mm endoscopes is an alternative to sedated endoscopy but
      is generally perceived as unacceptable to many American patients. Unsedated EGD
      using ultrathin 5-6-mm endoscopes is better tolerated. A randomized trial
      comparing unsedated ultrathin EGD (UT-EGD) with sedated conventional EGD (C-EGD)
      in a diverse American population is needed. METHODS: In this multicenter,
      randomized, controlled trial, 80 patients scheduled to undergo elective
      outpatient EGD were randomized to unsedated UT-EGD or sedated C-EGD. The study
      was carried out at San Francisco General Hospital, San Francisco Veterans Affairs
      Medical Center, and the Liver and Digestive Health Medical Clinic, San Jose.
      RESULTS: Baseline characteristics of patients randomized to unsedated UT-EGD and
      sedated C-EGD were similar. Moreover, there were no significant differences in
      overall patient satisfaction and willingness to repeat endoscopy in the same
      manner among the 2 study groups. There was, however, a significant difference in
      median total procedure time between the 2 study groups of 1.5 hours (P < 0.0001).
      The mean (+/- SD) total procedure cost was 512.4 US dollars (+/- 100.8 US
      dollars) for sedated C-EGD and 328.6 US dollars (+/- 70.3 US dollars) for
      unsedated UT-EGD (P < 0.0001). CONCLUSIONS: Patients undergoing unsedated UT-EGD
      are as satisfied as patients undergoing sedated C-EGD and are just as willing to
      repeat an unsedated UT-EGD. Unsedated UT-EGD was also faster, less costly, and
      may allow greater accessibility to this procedure.

PMID- 14724813
TI  - Expression of LL-37 by human gastric epithelial cells as a potential host defense
      mechanism against Helicobacter pylori.
AB  - BACKGROUND & AIMS: LL-37/human cationic antimicrobial peptide 18 (hCAP18) is a
      human cathelicidin with broad-spectrum antimicrobial, lipopolysaccharide binding,
      and chemotactic activities. This study examined the role of LL-37/hCAP18 in
      gastric innate immune defense by characterizing its constitutive and regulated
      expression by human gastric mucosa and its bactericidal activity against the
      gastric pathogen Helicobacter pylori. METHODS: LL-37/hCAP18 messenger RNA
      expression in normal and H. pylori -infected gastric mucosa and gastric
      epithelial cells was determined by in situ hybridization, real-time polymerase
      chain reaction, immunostaining, and immunoblot analysis. Bactericidal activity
      was measured by using a colony-forming unit assay. RESULTS: LL-37/hCAP18
      messenger RNA and protein were expressed in a distinct distribution by surface
      epithelial cells as well as chief and parietal cells in the fundic glands of
      normal gastric mucosa. LL-37/hCAP18 was significantly increased in the epithelium
      and gastric secretions of H. pylori -infected patients, but not in individuals
      with non-H. pylori -induced gastric inflammation. Infection of cultured gastric
      epithelial cells with a wild-type but not an isogenic Delta cagE mutant strain of
      H. pylori increased LL-37/hCAP18 expression, indicating that H. pylori -induced
      regulation of LL-37/hCAP18 production required an intact type IV secretion
      system. LL-37, the C-terminal peptide of LL-37/hCAP18, alone or in synergy with
      human beta-defensin 1, was bactericidal for several H. pylori strains.
      CONCLUSIONS: These data indicate that H. pylori up-regulates production of LL
      37/hCAP18 by gastric epithelium and suggest this cathelicidin contributes to
      determining the balance between host mucosal defense and H. pylori survival
      mechanisms that govern chronic infection with this gastric pathogen.

PMID- 14724814
TI  - Impact of lymph node staging on therapy of esophageal carcinoma.
AB  - BACKGROUND & AIMS: Therapy of esophageal carcinoma is stage dependent. The role
      of EUS-guided fine-needle aspiration (EUS FNA) in this setting is unclear. The
      aims of this study were to compare the performance characteristics of CT, EUS,
      and EUS FNA for preoperative nodal staging of esophageal carcinoma and to measure
      the impact of each staging test on treatment decisions. METHODS: From December
      1999 to March 2001, all patients with esophageal carcinoma seen at the Mayo
      Clinic Rochester were prospectively evaluated with CT, EUS, and EUS FNA. The
      impact of tumor stage on final therapy was assessed. RESULTS: A total of 125
      patients with esophageal carcinoma were enrolled. EUS FNA was more sensitive (83%
      vs. 29%; P < 0.001) than CT and more accurate than CT (87% vs. 51%; P < 0.001) or
      EUS (87% vs. 74%; P = 0.012) for nodal staging. Direct surgical resection was
      contraindicated in 77% of patients evaluated due to advanced
      locoregional/metastatic disease. Tumor location, patient age, comorbidities, and
      tumor stage determined by CT, EUS, and EUS FNA were associated with treatment
      decisions (P < 0.05). EUS FNA resulting in a higher/worse stage than CT (41
      patients) was associated with a greater rate of treatments that were not direct
      surgeries compared with cases in which the stage was the same or better.
      CONCLUSIONS: EUS FNA is more accurate for nodal staging and impacts on therapy of
      patients with esophageal carcinoma. EUS FNA should be included in the
      preoperative staging algorithm of these patients.

PMID- 14724815
TI  - Meta-analysis of the relationship between cagA seropositivity and gastric cancer.
AB  - BACKGROUND & AIMS: Reports in the literature regarding the relationship of
      infection with cagA -positive strains of Helicobacter pylori to gastric cancer
      over and above H. pylori infection alone are conflicting. The aim of this study
      was to estimate the magnitude of the risk for gastric cancer associated with cagA
      seropositivity and to identify any sources of heterogeneity between studies.
      METHODS: A meta-analysis of case-control studies with age- and sex-matched
      controls, which provided raw data on the infection rates with H. pylori and cagA
      strains of H. pylori as detected by serology or polymerase chain reaction DNA,
      was performed. RESULTS: A comprehensive literature search identified 16 qualified
      studies with 2284 cases and 2770 controls. H. pylori and cagA seropositivity
      significantly increased the risk for gastric cancer by 2.28- and 2.87-fold,
      respectively. Among H. pylori -infected populations, infection with cagA 
      positive strains further increased the risk for gastric cancer by 1.64-fold (95%
      confidence interval [CI], 1.21-2.24) overall and by 2.01-fold (95% CI, 1.21-3.32)
      for noncardiac gastric cancer. Gastric cancer at the cardia is not associated
      with H. pylori infection or cagA -positive strains of H. pylori. Patient age and
      site of gastric cancer contributed to the heterogeneity between studies.
      CONCLUSIONS: Infection with cagA -positive strains of H. pylori increases the
      risk for gastric cancer over the risk associated with H. pylori infection alone.
      Searching for cagA status over H. pylori infection may confer additional benefit
      in identifying populations at greater risk for gastric cancer.

PMID- 14724816
TI  - Cancer-attributable costs of diagnosis and care for persons with screen-detected
      versus symptom-detected colorectal cancer.
AB  - BACKGROUND & AIMS: Colorectal cancer screening is effective and cost-effective,
      but little data from health plan settings are available inform decision-makers
      regarding direct economic implications of colorectal cancer screening programs.
      The purpose of this study was to compare the prediagnosis evaluation and first
      year treatment costs of persons diagnosed with colorectal cancer, stratified by
      whether the cancer was detected by screening using fecal occult blood testing or
      evaluation of symptoms. METHODS: This retrospective study analyzed persons
      diagnosed with colorectal cancer from 1993 to 1999 in Group Health Cooperative, a
      large health maintenance organization in Washington state. Total health care
      costs during 3 months before and 12 months following diagnosis were compared for
      screen-detected versus symptom-detected individuals. RESULTS: During this time,
      206 cancers were detected by screening and 717 by symptoms. In the 3 months
      before diagnosis, total costs were 7346 US dollars for persons with screen
      detected versus 10,042 US dollars for those with symptom-detected cancer (P <
      0.01). Stratified by stage, diagnosis costs were significantly lower for persons
      with stage B cancer (7282 US dollars vs. 11,682 US dollars ; P < 0.01) and
      nonsignificantly lower for other stages. A total of 53% of screen-detected cases
      were Dukes' stage A or in situ at diagnosis versus 30% of symptom-detected cases
      (P < 0.01). Overall costs were lower for the screen-detected group in the 12
      months following diagnosis (22,369 US dollars vs. 29,471 US dollars; P < 0.01).
      CONCLUSIONS: Colorectal cancer screening can substantially reduce prediagnosis
      evaluation costs. These savings are of interest to health plans and should be
      factored into cost-effectiveness evaluations of screening programs.

PMID- 14724817
TI  - Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression
      in postinfectious IBS.
AB  - BACKGROUND & AIMS: Both psychological and mucosal changes (increased
      enterochromaffin [EC] cells and T lymphocytes) have been associated with
      postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have
      been underpowered to determine the relative importance of these changes in
      predicting the development of PI-IBS. Our aim was to prospectively determine the
      relative importance of both psychological and histologic factors in the
      development of PI-IBS after Campylobacter infection. METHODS: Questionnaires
      detailing psychological and bowel symptoms were sent to 1977 patients 3 months
      after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex
      matched patient controls who were asymptomatic after infection, and 34 healthy
      volunteers underwent rectal biopsy, which was assessed for serotonin-containing
      EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS,
      predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%)
      of those infected. EC cell counts per high-power field (hpf) were higher in
      patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9;
      P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes
      per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls
      (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P
      = 0.058, respectively). Anxiety, depression, and fatigue were significantly
      increased in patients with PI-IBS compared with patient controls. Multivariate
      analysis indicated that increased EC cell counts and depression were equally
      important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each
      standard deviation increase in respective values). CONCLUSIONS: Both increased EC
      cells and depression are important independent predictors of developing PI-IBS.

PMID- 14724818
TI  - Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult
      patients for up to 11.5 years.
AB  - BACKGROUND & AIMS: Primary eosinophilic esophagitis is a chronic, increasingly
      recognized, interleukin 5-driven inflammatory disorder of the esophagus. The
      leading symptom in adults is uniform attacks of dysphagia, and the established
      histologic sign is a dense eosinophilic infiltration of the esophageal
      epithelium. Before this study, the natural course of eosinophilic esophagitis had
      not been defined and information regarding potential long-term risks was lacking.
      METHODS: This prospective case series included 30 adult patients with
      eosinophilic esophagitis (22 men and 8 women; mean age, 40.6 years) whose
      diagnosis had been made >1 year before study debut based on typical history,
      consistent endoscopic abnormalities, and infiltration of the esophageal
      epithelium with >24 eosinophils/high-power field. After a mean of 7.2 years,
      patients underwent a comprehensive follow-up examination. RESULTS: All patients
      survived the study period in good health and stable nutritional state. Dysphagia
      persisted in 29 patients, exerting a major negative effect on socioprofessional
      activities on 1 patient and a minor impact on 15. Attacks of dysphagia were more
      frequent in patients with blood eosinophilia or pronounced endoscopic
      alterations. The esophageal eosinophilic infiltration persisted in all
      symptomatic patients, but cell numbers spontaneously decreased significantly
      (78.7 vs. 40.3 cells/high-power field). The inflammatory process evoked fibrosis
      of the esophageal lamina propria but did not spread to the stomach or duodenum.
      No case evolved to a hypereosinophilic syndrome. CONCLUSIONS: Eosinophilic
      esophagitis, a primary and chronic disease restricted to the esophagus, leads to
      persistent dysphagia and structural esophageal alterations but does not impact
      the nutritional state. To date, no malignant potential has been associated with
      this disease.

PMID- 14724819
TI  - Screening for Barrett's esophagus in colonoscopy patients with and without
      heartburn.
AB  - BACKGROUND & AIMS: The population prevalence of Barrett's esophagus (BE) is
      uncertain. Our aim was to describe the prevalence of BE in a volunteer
      population. METHODS: Upper endoscopy (EGD) was performed in 961 persons with no
      prior history of EGD who were scheduled for colonoscopy. Symptom questionnaires
      were completed prior to endoscopy. Biopsy specimens were taken from the gastric
      cardia and any columnar mucosa extending > or =5 mm into the tubular esophagus
      and from the stomach for H. pylori infection in the last 812 patients. RESULTS:
      The study sample was biased toward persons undergoing colonoscopy, males, and
      persons with upper GI symptoms. The prevalence of BE was 65 of 961 (6.8%)
      patients, including 12 (1.2%) with long-segment BE (LSBE). Among 556 subjects who
      had never had heartburn, the prevalences of BE and LSBE were 5.6% and 0.36%,
      respectively. Among 384 subjects with a history of any heartburn, the prevalences
      of BE and LSBE were 8.3% and 2.6%, respectively. In a univariate analysis, LSBE
      was more common in those with any heartburn vs. those with no heartburn (P =
      0.01), but the sample size was insufficient to allow multivariate analysis of
      predictors of LSBE. In a multivariate analysis, BE was associated with increasing
      age (P = 0.02), white race (P = 0.03), and negative H. pylori status (P = 0.04).
      Overall, BE was not associated with heartburn, although heartburn was more common
      in persons with LSBE or circumferential short segments. CONCLUSIONS: LSBE is very
      uncommon in patients who have no history of heartburn. SSBE is relatively common
      in persons age > or =40 years with no prior endoscopy, irrespective of heartburn
      history.

PMID- 14724820
TI  - Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant
      enzyme in the endoplasmic reticulum.
AB  - BACKGROUND & AIMS: Congenital sucrase-isomaltase deficiency (CSID) is an
      autosomal recessive human disorder characterized by reduced activities of the
      brush border enzyme sucrase-isomaltase (SI). Here, we elucidate the pathogenesis
      of a new variant of CSID at the cellular and molecular level. METHODS: Assessment
      of the CSID phenotype was achieved by enzymatic activity measurements,
      biosynthetic labeling of intestinal biopsy specimens, immunoprecipitation of SI,
      and immunoelectronmicroscopy. The putative mutation was identified by sequencing
      of the SI cDNA isolated by RT-PCR from intestinal biopsy samples. The function of
      the mutation was verified by immunoprecipitation and confocal microscopy of
      transiently transfected cells. RESULTS: Biosynthetic labeling and immunoelectron
      microscopy reveal a predominant localization of SI in the endoplasmic reticulum
      (ER) similar to phenotype I of CSID. Unlike phenotype I, however, a partial
      conversion of SI to a complex glycosylated mature form takes place. The SI cDNA
      in this phenotype revealed 3 mutations, 2 of which, Val to Phe at residue 15 and
      Ala to Thr at residue 231, had no effect on the structure or function of SI. By
      contrast, the third mutation resulted in an exchange of leucine by proline at
      position 620 (L620P) and revealed in transfected COS cells structural features
      and subcellular localization similar to the phenotype identified in the patient's
      enterocytes. CONCLUSIONS: This is the first identification at the molecular and
      subcellular levels of a novel variant of CSID in which SI accumulates
      predominantly in the ER, and a minor proportion is further processed and
      transported to the apical membrane of enterocytes.

PMID- 14724821
TI  - An upstream polymorphism associated with lactase persistence has increased
      enhancer activity.
AB  - BACKGROUND & AIMS: Intestinal lactase activity declines during childhood in some
      humans. This phenotypic polymorphism of lactase persistence or nonpersistence
      into adult life has been shown in a recent study to be 100% associated with a T/C
      nucleotide polymorphism at position -13910 and approximately 97% with an A/G
      nucleotide polymorphism at position -22018. The aim of this study was to
      investigate the role of these nucleotide polymorphisms for lactase-phlorizin
      hydrolase (LPH) gene expression. METHODS: The -13910 and -22018 regions were
      cloned from lactase-persistent and -nonpersistent individuals, and the regions
      were analyzed for gene regulatory activity of a luciferase reporter gene by
      transfection experiments using the intestinal cell line Caco-2. Electrophoretic
      mobility shift assays (EMSAs) were used to investigate protein/DNA interactions
      with the -13910 sequence. RESULTS: We show that the -13910 region contains a
      strong enhancer. The -13910 regions from both lactase persistent (-13910T
      variant) and lactase nonpersistent (-13910C variant) have enhancer activity.
      However, the -13910T variant enhances the LPH promoter approximately 4 times more
      than the -13910C variant when analyzed in differentiated Caco-2 cells. A nuclear
      factor from both an intestinal and a nonintestinal extract binds strongly to the 
      13910T variant whereas the binding to the -13910C variant is much weaker.
      CONCLUSIONS: The discovery of a functional difference between the 2 alleles at
      position -13910 supports the notion that the molecular difference between lactase
      persistence and nonpersistence is caused by the mutation at position -13910.

PMID- 14724822
TI  - Insulin resistance is associated with chronic hepatitis C virus infection and
      fibrosis progression [corrected].
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus infection is associated with an
      increased prevalence of type 2 diabetes. We hypothesized that virus-induced
      insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C
      virus infection. METHODS: In 260 hepatitis C virus-infected subjects, we examined
      the relationship between histological findings and anthropometric and biochemical
      data, including insulin resistance determined by the homeostasis model assessment
      (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels
      between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic
      fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist
      hip ratio. RESULTS: Hepatitis C virus-infected subjects with stage 0 or 1 hepatic
      fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P < or = 0.01)
      compared with matched healthy controls. In the 250 hepatitis C virus patients
      (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation
      were univariate predictors of HOMA-IR. By multiple linear regression analysis,
      independent predictors of HOMA-IR included body mass index (P < 0.001), previous
      failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001),
      and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than
      other genotypes (which were comparable when adjusted for effects of the remaining
      independent predictors). HOMA-IR was an independent predictor for the degree of
      fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03).
      CONCLUSIONS: Hepatitis C virus may induce insulin resistance irrespective of the
      severity of liver disease, and this effect seems to be genotype specific.
      Further, our findings support the hypothesis that insulin resistance may
      contribute to fibrotic progression in chronic hepatitis C virus infection.

PMID- 14724823
TI  - Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Although considerable effort has been directed toward the
      mapping of peptide epitopes by autoantibodies, the role of nonprotein molecules
      has been less well studied. The immunodominant autoantigen in primary biliary
      cirrhosis (PBC), E2 components of pyruvate dehydrogenase complexes (PDC-E2), has
      a lipoate molecule bonded to the domain to which autoantibodies are directed.
      METHODS: We examined sera from patients with PBC (n = 105), primary sclerosing
      cholangitis (n = 70), and rheumatoid arthritis (n = 28) as well as healthy
      volunteers (n = 43) for reactivity against lipoic acid. The lipoic acid hapten
      specificity of the reactive antibodies in PBC sera was determined following
      incubation of aliquots of the sera with human serum albumin (HSA), lipoylated HSA
      (HSA-LA), PDC-E2, lipoylated PDC-E2, polyethylene glycol (PEG), lipoylated PEG,
      free lipoic acid, and synthetic molecular mimics of lipoic acid. RESULTS: Anti
      lipoic acid specific antibodies were detected in 81% (79 of 97) of
      antimitochondrial antibody (AMA)-positive patients with PBC but not in controls.
      Two previously unreported specificities in AMA-positive sera that recognize free
      lipoic acid and a carrier-conjugated form of lipoic acid were also identified.
      CONCLUSIONS: We hypothesize that conjugated form(s) of native or xenobiotic
      lipoic acid mimics contribute to the initiation and perpetuation of autoimmunity
      by at first breaking self-tolerance and participating in subsequent determinant
      spreading. The variability in the immunoreactive carrier/lipoate conjugates
      provides an experimental framework on which potential mechanisms for the
      breakdown of self-tolerance following exposure to xenobiotics can be
      investigated. The data have implications for patients taking lipoic acid as a
      dietary supplement.

PMID- 14724824
TI  - Long-term safety of lamivudine treatment in patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: Data on the long-term safety of lamivudine are limited. The
      aim of this analysis was to determine the incidence of hepatitis flares, hepatic
      decompensation, and liver-disease-related (LDR) serious adverse events (SAE)
      during long-term lamivudine treatment. METHODS: We reviewed data on 998 patients
      with HBeAg-positive compensated chronic hepatitis B who received lamivudine for
      up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year.
      RESULTS: Hepatitis flares occurred in 10% of the lamivudine-treated patients in
      year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis
      flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in
      year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated
      patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60
      LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of
      patients with a documented lamivudine-resistant mutation increased from 23% in
      year 1 to 65% in year 5. During each year of the study, patients with lamivudine
      resistant mutations experienced significantly more hepatitis flares than patients
      without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic
      decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine
      resistance remained stable during the first 4 years with mutations and increased
      afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. CONCLUSIONS: This
      study demonstrated that lamivudine treatment for up to 6 years has an excellent
      safety profile in patients with HBeAg-positive compensated liver disease, but
      patients with long-standing lamivudine-resistant mutations may experience
      worsening liver disease.

PMID- 14724825
TI  - Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma:
      systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: The aim of our study was to conduct a systematic review of
      studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non
      Hodgkin's lymphoma (B-NHL) and to perform a meta-analysis of case-control studies
      comparing this prevalence with that of a reference group. METHODS:  DATA SOURCES:
      Electronic databases and the Cochrane Controlled Trials Register. STUDY
      SELECTION: Studies evaluating prevalence of HCV infection in patients with B-NHL.
      Studies comparing HCV prevalence in B-NHL (cases) and in a reference group
      (controls) were included in the meta-analysis. DATA EXTRACTION: Author/country,
      diagnostic method (serology/PCR), control type, matching/design, and VHC
      prevalence. DATA SYNTHESIS: Prevalence of HCV infection and meta-analysis
      combining the odds ratios (OR). RESULTS: Forty-eight studies (5542 patients) were
      identified. Mean HCV infection prevalence was 13% (95% CI: 12%-14%), which was
      higher in Italy (20%) and Japan (14%). Ten studies compared HCV prevalence in B
      NHL (17%) and healthy controls (1.5%) (OR: 10.8; 95% CI: 7.4-16), results being
      homogeneous; OR increased up to 14.1 when only Italian studies were considered.
      Sixteen studies compared HCV prevalence in B-NHL (13%) and in other hematologic
      malignancies (2.9%) (OR: 4.2; 95% CI: 2.5-7), also with homogeneous results; OR
      increased up to 7.8 when subanalysis included only Italian studies. CONCLUSIONS:
      HCV prevalence in patients with B-NHL is approximately 15%, higher than that
      reported not only in general population (1.5%) but also in patients with other
      hematologic malignancies (2.9%), suggesting a role of HCV in the etiology of B
      NHL. The striking geographic variation in this association suggests that genetic
      and/or environmental factors are also involved in the pathogenesis of this
      disorder.

PMID- 14724826
TI  - Cancer risk in patients with hereditary hemochromatosis and in their first-degree
      relatives.
AB  - BACKGROUND & AIMS: Iron overload may be carcinogenic. Patients with hereditary
      hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer,
      but the reported risks for nonhepatobiliary cancers are conflicting. The risk of
      cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is
      unknown. This study aimed to better assess these risks. METHODS: We performed a
      population-based cohort study of 1847 Swedish patients with HH and 5973 of their
      first-degree relatives using nationwide, population-based health and census
      registers. We used standardized incidence ratios (SIRs) as relative risk.
      RESULTS: With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH
      were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [CI], 16
      22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% CI, 1.0
      1.4), including nonelevated risks for several gastrointestinal tract cancers. At
      10 years of follow-up, the absolute risk of liver cancer was 6% among men and
      1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first
      degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95%
      CI, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a
      modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI, 1.0
      2.4), the histopathologic spectrum of which differed from the patients.
      CONCLUSIONS: Patients (particularly men) with HH are at increased risk for
      hepatocellular cancer, although the magnitude of the risk is lower than previous
      estimates. Overall cancer risk in first-degree relatives does not seem to be
      increased.

PMID- 14724827
TI  - Early is superior to deferred preemptive lamivudine therapy for hepatitis B
      patients undergoing chemotherapy.
AB  - BACKGROUND & AIMS: Hepatitis B virus reactivation is a serious cause of morbidity
      and mortality in hepatitis B surface antigen-positive patients treated with
      chemotherapy. We compared the efficacy of early and deferred preemptive
      lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B
      virus reactivation in hepatitis B surface antigen-positive lymphoma patients
      treated with chemotherapy. METHODS: Thirty consecutive hepatitis B surface
      antigen-positive lymphoma patients undergoing intensive chemotherapy were
      randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy
      (group 1) or to have this treatment deferred until there was serological evidence
      of hepatitis B virus reactivation on the basis of serial 2-week-interval serum
      hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2).
      RESULTS: Eight (53%) patients in group 2 and none in group 1 had hepatitis B
      virus virological reactivation after chemotherapy (P = 0.002). Seven patients in
      group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1
      hepatic failure). Survival free from hepatitis due to hepatitis B virus
      reactivation in group 1 patients was significantly longer than that in group 2 (P
      = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation
      in these patients was 16 weeks (range, 4-36 weeks) after the initiation of
      chemotherapy. Three (13%) of the 23 patients treated with lamivudine had
      hepatitis B virus-related hepatitis after lamivudine withdrawal. CONCLUSIONS:
      Lamivudine should be considered preemptively before or at the initiation of
      chemotherapy for all hepatitis B surface antigen-positive lymphoma patients
      undergoing intense chemotherapy.

PMID- 14724828
TI  - A murine model of chronic inflammation-induced intestinal fibrosis down-regulated
      by antisense NF-kappa B.
AB  - BACKGROUND & AIMS: To elucidate extracellular matrix (ECM) changes underlying
      intestinal fibrosis, a frequent complication of inflammatory bowel disease, we
      developed a murine model of chronic colitis associated with intestinal fibrosis.
      METHODS: Chronic inflammation was established by weekly intrarectal
      administration of trinitrobenzene sulfonic acid (TNBS). In 2 variations of the
      model an antisense oligonucleotide for nuclear factor kappa B (NF-kappa B) p65
      was given prophylactically or therapeutically to block chronic inflammation
      associated fibrosis. Colonic inflammation and fibrosis were determined by
      histology. Total collagen level was estimated by hydroxyproline quantification.
      Colonic expression of collagens (Col1a2, Col3a2), ECM remodeling genes (matrix
      metalloproteinase [MMP]-1, -3, and tissue inhibitor of matrix metalloproteinase
      [TIMP]-1), and inflammation-modulating cytokines (tumor necrosis factor alpha
      [TNF-alpha], interferon gamma [IFN-gamma], transforming growth factor beta 1 [TGF
      beta 1], and insulin-like growth factor 1 [IGF-1]) were assessed by
      semiquantitative reverse-transcription polymerase chain reaction. Control and
      TNBS-treated colonic mesenchymal cells were characterized by morphology,
      phenotype, and functional response to TNF-alpha and IFN-gamma. RESULTS: Colons of
      TNBS-treated mice contained acute and chronic inflammatory infiltrates, increased
      collagen, fibrogenic tissue architecture, and increased expression of TNF-alpha,
      TGF-beta 1, IGF-1, Col1a2, MMP-1, and TIMP-1. Colonic mesenchymal cells from TNBS
      treated mice were also morphologically distinct from those of the control mice,
      with increased TIMP-1 expression in response to IFN-gamma treatment. Fibrosis
      persisted for 2-4 weeks after cessation of the TNBS treatment. In mice given NF
      kappa B antisense prophylactically, 67% were fibrosis-free, whereas of those
      treated after establishing chronic inflammation, 43% were free of fibrosis.
      CONCLUSIONS: Extended TNBS treatment of mice yielded chronic intestinal
      inflammation-associated fibrosis with extensive fibrogenic ECM changes that could
      be counteracted by specific blockade of NF-kappa B.

PMID- 14724830
TI  - Impaired gastric secretion and lack of trophic responses to hypergastrinemia in
      M3 muscarinic receptor knockout mice.
AB  - BACKGROUND & AIMS: The physiologic significance of the M(3) muscarinic receptor
      is unclear due to an absence of specific ligand. In the present study, M(3)
      receptor knockout (KO) mice were used to elucidate the role of M(3) receptors in
      gastric acid secretion and gastric mucosal integrity. METHODS: M(3) KO versus
      wild-type mice aged 1 month to 2 years were included. Gastric acid secretion was
      assessed by both direct intragastric pH measurement and pylorus ligation. Serum
      gastrin and gastric mucosal histamine levels were determined by radioimmunoassay
      and enzyme-linked immunosorbent assay, respectively. Morphologic analysis was
      performed by both immunohistochemistry and transmission electron microscopy.
      RESULTS: Fasted M(3) KO mice exhibited higher intragastric pH, lower acid output
      after pylorus ligation, a lower proportion of active parietal cells, and higher
      serum gastrin levels than fasted wild-type mice. Acid secretion in response to
      carbachol, histamine, gastrin 17, and 2-deoxy-D-glucose was impaired in the
      mutant mice. Although carbachol was still able to cause approximately 30% acid
      output in M(3) KO mice, the acid secretion was inhibited by pirenzepine or
      famotidine. Despite remarkable hypergastrinemia in M(3) KO mice, there were no
      trophic responses in the oxyntic mucosa with respect to the mucosal thickness,
      proliferation rate, and numbers of parietal and enterochromaffin-like cells.
      Cholecystokinin type 2 receptor antagonist YM022 was without the effect in M(3)
      KO mice. CONCLUSIONS: The present study shows that M(3) receptors are essential
      for basal acid secretion, a fully acid secretory response to histamine and
      gastrin, and the trophic responses of oxyntic mucosa to gastrin.

PMID- 14724829
TI  - Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid
      colitis in mice.
AB  - BACKGROUND & AIMS: Indoleamine 2,3-dioxygenase (IDO), an interferon gamma-induced
      intracellular enzyme, inhibits lymphocyte proliferation through tryptophan
      degradation. IDO is highly expressed in the mammalian intestine. We sought to
      determine whether IDO played a regulatory role in the T-cell helper 1 (Th1)
      mediated trinitrobenzene sulfonic acid (TNBS) model of colitis. METHODS:
      Intrarectal TNBS was given to SJL/J mice along with either placebo or a specific
      IDO inhibitor. IDO protein and mRNA expression were assessed by Western blotting
      and real-time PCR. Colonic lamina propria mononuclear cells (LPMNCs) were
      isolated, fractionated, and cultured, in the presence and absence of IFN-gamma,
      to determine the cell type(s) expressing IDO. RESULTS: IDO is expressed by
      professional antigen-presenting cells in the lamina propria. Induction of TNBS
      colitis resulted in a significant increase in IDO mRNA (P = 0.005) and protein
      expression. IDO inhibition during TNBS colitis resulted in an 80% mortality
      compared with 10% for placebo-treated animals (P = 0.0089). IDO inhibition
      resulted in a more severe colitis both histologically and morphologically (P <
      0.05) and significantly increased colonic proinflammatory cytokine expression
      compared with placebo-treated animals. CONCLUSIONS: IDO is expressed in the
      normal colon and is up-regulated in the setting of TNBS colitis. Inhibition of
      IDO during TNBS colitis resulted in increased mortality and an augmentation of
      the normal inflammatory response. These findings suggest that IDO plays an
      important role in the down-regulation of Th1 responses within the
      gastrointestinal tract.

PMID- 14724831
TI  - Colonic bacterial superantigens evoke an inflammatory response and exaggerate
      disease in mice recovering from colitis.
AB  - BACKGROUND & AIMS: There is renewed interest in commensal bacteria as triggers of
      idiopathic disease, a concept that is prominent in inflammatory bowel disease
      (IBD). Here the effect of intracolonic instillation of Staphylococcus aureus
      enterotoxin B (SEB), a model superantigen (SAgs: potent T-cell stimuli), into
      mice was examined. METHODS: Mice (Balb/c, severe combined immunodeficient [SCID],
      V beta 8(+) ovalbumin transgenic [OVA-Tg], interleukin 10 [IL-10] knockout [KO])
      received a single intrarectal (IR) dose of SAg and colonic form (histology,
      myeloperoxidase [MPO] activity) and function (ion transport) were assessed 12-72
      hours later. In subsequent studies the potential for SEB to reactivate disease in
      mice recovering from dextran sodium sulfate (DSS)-induced colitis (5 days at 4%
      [wt/vol] followed by 14 days normal water) was examined. RESULTS: SEB-treated
      Balb/c mice displayed a time- and dose-dependent colonic inflammation (increased
      MPO, histologic damage score, and macrophage number). Similar events occurred in
      response to other SAgs, namely S. aureus enterotoxin A (SEA) and Yersinia
      pseudotuberculosis mitogen. Ion transport, the driving force for water movement,
      was unaffected by SEB treatment. SCID mice developed no inflammation after IR SEB
      delivery, whereas OVA Tg mice displayed enhanced responsiveness. Although SEB
      treatment of IL-10 KO mice did elicit a response, the inflammation was transitory
      and did not hasten the spontaneous colitis seen in these mice. Finally, mice
      recovering from DSS-induced colitis showed a worsening of the disease when
      challenged with SEB; IR SEB evoked significant increases in MPO, macrophage
      infiltration, T-cell activation (i.e., CD25 expression), and perturbed epithelial
      ion transport. CONCLUSIONS: Lumen-derived bacterial SAgs can elicit a local
      inflammation and aggravate enteric inflammatory disorders in which they were not
      the causative agent.

PMID- 14724833
TI  - Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon.
AB  - BACKGROUND & AIMS: Although the hepatitis C virus (HCV) subgenomic replicon
      system has been widely used in the study of HCV, this system is available only
      for a few related genotypes. To develop a new replicon system, the genotype 2a
      clone JFH-1 was isolated from a patient with fulminant hepatitis. METHODS: A
      genotype 2a replicon was constructed by isolating the consensus sequence of JFH
      1, transfecting G418-selectable subgenomic transcripts into Huh7 cells, and
      estimating the replication efficiency. RESULTS: The colony formation efficiency
      of the JFH-1 replicon was 53,200 colonies/microg RNA, significantly higher than
      that of the genotype 1b cell-adapted replicon, at 909 colonies/microg RNA (P <
      0.05). The JFH-1 replicon RNA was transmissible to naive Huh7 cells by
      transfection of cellular RNA from cells containing the replicon. Sequencing of
      cloned replicon RNAs revealed that all but 1 had at least 1 nonsynonymous
      mutation. One of these mutations was shown to enhance the colony formation
      efficiency of the JFH-1 replicon. Furthermore, the JFH-1 replicon RNA replicated
      efficiently without G418 selection in a transient replication assay. CONCLUSIONS:
      The genotype 2a subgenomic replicon was established in Huh7 cells and replicated
      efficiently with or without G418 selection. This subgenomic replicon could
      replicate without common amino acid mutations; however, some of the mutations
      found in the clones might be important in conferring higher replication
      phenotypes. This system provides a powerful new tool for researching HCV.

PMID- 14724832
TI  - Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.
AB  - BACKGROUND & AIMS: Obesity is one of the risk factors for liver fibrosis, in
      which plasma adiponectin, an adipocytokine, levels are decreased. Hepatic
      stellate cells play central roles in liver fibrosis. When they are activated,
      they undergo transformation to myofibroblast-like cells. Adiponectin suppresses
      the proliferation and migration of vascular smooth muscle cells, whose
      characteristics are similar to those of hepatic stellate cells. Adiponectin could
      have biological significances in liver fibrosis. METHODS: The role of adiponectin
      on liver fibrosis induced by the administration of carbon tetrachloride twice a
      week for 12 weeks was tested by using adiponectin-knockout mice and an adenovirus
      mediated adiponectin-expression system. We also investigated the effect of
      adiponectin in activated hepatic stellate cells. RESULTS: When mice were
      administered carbon tetrachloride (300 microL/kg body weight) twice a week for 12
      weeks, knockout mice showed extensive liver fibrosis with an enhanced expression
      of transforming growth factor-beta 1 and connective tissue growth factor compared
      with wild-type mice (P < 0.05). Injection of adenovirus producing adiponectin
      (AdADN) before carbon tetrachloride (1000 microL/kg body weight) treatment
      prevented liver fibrosis in wild-type mice (P < 0.001). Injection of AdADN at 6
      weeks attenuated liver fibrosis even though carbon tetrachloride was given for an
      additional 6 weeks (total of 12 weeks). In cultured hepatic stellate cells,
      adiponectin suppressed platelet-derived growth factor-induced proliferation and
      migration and attenuated the effect of transforming growth factor-beta 1 on the
      gene expression of transforming growth factor-beta 1 and connective tissue growth
      factor and on nuclear translocation of Smad2. CONCLUSIONS: The findings indicate
      that adiponectin attenuates liver fibrosis and could be a novel approach in its
      prevention.

PMID- 14724834
TI  - Binge ethanol exposure increases liver injury in obese rats.
AB  - BACKGROUND & AIMS: The objective of this study was to address the hepatic effects
      of acute alcohol consumption in obesity by simulating an alcohol binge in
      genetically obese fa/fa rats compared with lean Fa/? rats. METHODS: Ethanol 4
      g/kg or saline was administered by gavage every 12 hours for 3 days. RESULTS:
      Plasma alcohol levels were similar in both groups. Binge ethanol exposure caused
      liver injury in obese fa/fa but not in lean Fa/? rats, as assessed by alanine
      aminotransferase and H&E staining. Obesity impaired the antioxidant defense
      because basal levels of glutathione, glutamate cysteine ligase modulatory
      subunit, catalase, glutathione reductase, and superoxide dismutase were lower in
      fa/fa compared with Fa/? rats; the ethanol binge further decreased these
      antioxidants in fa/fa rats and also decreased glutathione peroxidase activity.
      Nonesterified fatty acids and lipid peroxidation were increased after ethanol
      treatment in fa/fa rats. Cytochrome P450 2E1 was down-regulated in fa/fa compared
      with Fa/? rats; however, the ethanol binge increased cytochrome P450 2E1 in both
      genotypes. Adenosine triphosphate decreased and uncoupling protein 2 increased in
      fa/fa rats treated with ethanol. 3-Nitrotyrosine protein adducts were detected
      only in fa/fa rats treated with ethanol, and this was accompanied by an induction
      of inducible nitric oxide synthase. Ethanol binge increased caspase-3 and caspase
      8 activity, the expression of Fas ligand, and terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling in fa/fa rats.
      CONCLUSIONS: These data indicate that binge drinking increases apoptosis and
      liver injury in obese rats more than in lean controls and suggest that the injury
      may involve oxidative and nitrosative damage.

PMID- 14724835
TI  - Inducible nitric oxide synthase is required in alcohol-induced liver injury:
      studies with knockout mice.
AB  - BACKGROUND & AIMS: Oxidative stress contributes to early alcohol-induced liver
      injury, and superoxide (O(2)*-) production from NADPH oxidase plays a key role.
      However, the production of the free radical nitric oxide (NO*) by inducible
      nitric oxide synthase (iNOS) could also be involved. METHODS: To test this
      hypothesis, iNOS knockout (B6.129P2-Nos2 (tm1 Lau)) and wild-type mice were fed
      high-fat control or ethanol-containing diets for 4 weeks. RESULTS: Mean body
      weight gains were not significantly different between treatment groups, and
      average urine ethanol concentrations were similar in wild-type and iNOS knockout
      mice. After 4 weeks, serum alanine aminotransferase (ALT) levels were increased
      significantly about 4-fold over control values (29 +/- IU/L) by enteral ethanol
      (113 +/- 20) in wild-type mice; this effect of ethanol was significantly blunted
      in iNOS knockout mice (50 +/- 9). Similar protective effects against liver damage
      were observed if wild-type mice were treated with the iNOS inhibitor N -(3
      aminomethyl)benzyl-acetamindine (1400W). Enteral ethanol also caused severe fatty
      accumulation, mild inflammation, and necrosis in the liver in wild-type mice but
      had no effect in iNOS knockout mice. The accumulation of 4-hydroxynonenal (lipid
      peroxidation) and 3-nitrotyrosine (reactive nitrogen species formation) protein
      adducts caused by alcohol was completely blocked in iNOS knockout mice.
      CONCLUSIONS: These data strongly support the hypothesis that iNOS is required for
      the pathogenesis of early alcohol-induced hepatitis by production of nitric oxide
      derived pro-oxidants (e.g., peroxynitrite).

PMID- 14724836
TI  - Nonoxidative ethanol metabolites alter extracellular matrix protein content in
      rat pancreas.
AB  - BACKGROUND & AIMS: The mechanisms involved in ethanol-induced pancreas fibrosis
      are poorly understood. Here we show that fatty acid ethyl esters (FAEEs),
      nonoxidative ethanol metabolites, increase extracellular matrix (ECM) protein
      levels in pancreas. METHODS: Rat pancreatic acini were incubated for 1-4 hours
      with FAEEs or acetaldehyde. In another set of experiments, rats received an
      intravenous infusion of FAEEs for 6 hours. Collagens were assessed by a
      hydroxyproline assay. Laminin and fibronectin were analyzed by Western blotting.
      Gene expression of ECM proteins was measured by conventional and real-time
      reverse-transcription polymerase chain reaction (RT-PCR). Matrix
      metalloproteinase (MMP), plasmin, and urokinase-type plasminogen activator (uPA)
      activities were determined by zymography and fluorogenic assays. RESULTS: FAEEs
      increased collagen, laminin, and fibronectin levels in pancreatic acini without
      affecting messenger RNA (mRNA) expression for these proteins. Actinomycin D, a
      transcriptional inhibitor, did not block the increase in ECM proteins induced by
      FAEEs. FAEEs reduced the activity of the serine protease, plasmin, and that of
      the uPA. Consistent with these results, the serine protease inhibitor aprotinin
      reproduced the effects of FAEEs and prevented the further increase in ECM
      proteins induced by FAEEs. In vivo administration of FAEEs reduced plasmin and
      uPA activities and increased ECM protein levels in pancreas. Acetaldehyde had
      minor effects on ECM protein levels and did not affect plasmin activity.
      CONCLUSIONS: FAEEs increase ECM protein levels in pancreas. The results suggest
      that this effect is caused primarily by an inhibition in ECM degradation via
      serine proteases including the plasminogen system.

PMID- 14724837
TI  - Nausea and vomiting.

PMID- 14724838
TI  - Wilson disease.

PMID- 14724839
TI  - Presidential address. Through strategic planning the American Gastroenterological
      Society will be even stronger in the future.

PMID- 14724840
TI  - Mortality in inflammatory bowel disease: peril and promise.

PMID- 14724841
TI  - EUS FNA staging of esophageal cancer.

PMID- 14724842
TI  - Insulin resistance and tissue repair: a "fato-logical" phenomenon.

PMID- 14724843
TI  - A mouse model of intestinal fibrosis?

PMID- 14724844
TI  - Hepatitis C virus replicons finally get to second base.

PMID- 14724845
TI  - Hello, Mr. Clips--could you chip in please?

PMID- 14724846
TI  - Lactulose breath testing, bacterial overgrowth, and IBS: just a lot of hot air?

PMID- 14724848
TI  - Hirschsprung lost his nerve.

PMID- 14724849
TI  - Infliximab at 5 years--tweaking the recipe for success?

PMID- 14724850
TI  - Occult HBV infection--both hidden and mysterious.

PMID- 14724869
TI  - A prospective, randomized pilot evaluation of topical triple antibiotic versus
      mupirocin for the prevention of uncomplicated soft tissue wound infection.
AB  - Little data exists comparing the safety and efficacy of triple antibiotic
      ointment (TAO) and mupirocin for prevention of uncomplicated soft tissue wound
      infections. The purpose of this investigation was to conduct a pilot study of the
      relative safety, efficacy, and cost effectiveness of the 2 preparations. This was
      a randomized, prospective, interventional study to determine the difference in
      infection rates of uncomplicated soft tissue wounds between subjects treated with
      TAO and mupirocin ointment after standard wound care and suturing. Subjects were
      enrolled at presentation to the ED if they met the study inclusion criteria and
      were required to make one follow-up visit to the ED to determine the status of
      their wound (infected vs. not infected). A total of 99 patients were enrolled and
      assessed at the follow-up visit. The groups had similar rates of self-reported
      compliance with wound care and dressing changes. Patients in the mupirocin group
      had a greater rate of signs of infection (12% vs. 6.1%), and infection (4% vs.
      0%) compared with patients in the TAO group, although neither difference achieved
      statistical significance. There were no serious adverse effects in either group.
      This pilot study found a similar rate of wound infection and adverse events
      between TAO and mupirocin ointments. Results should be confirmed in a larger
      equivalency trial.

PMID- 14724870
TI  - Evaluation of an end-tidal portable ETCO2 colorimetric breath indicator
      (COLIBRI).
AB  - Evaluation of tube position is important after in-hospital and prehospital
      emergency intubation. Colorimetric breath indicators are devices for immediate
      control of tube positioning by showing a color change according to end-tidal CO2
      (ETCO2) concentrations. We hypothesized that colorimetric breath indicators can
      yield reliable results for confirmation of tube position. The aim of this study
      was to evaluate the effectiveness and safety of a new colorimetric breath
      indicator (Colibri, ICOR AB, Bromma, Sweden) in 147 patients during general
      anesthesia, in critically ill patients, during transport to in-hospital
      interventions, and in a study design after insertion of a second tube into the
      esophagus in long-term ventilated patients. The Colibri was attached between the
      respective airway and ventilatory tubing. Seventy-three patients were
      investigated during general anesthesia, 39 patients were observed during long
      term ventilation with an average duration of 33 hours, in 15 patients during
      transport to an intervention for up to 4 hours, and in 20 long-term ventilated
      patients at the medical intensive-care unit after insertion of a second tube
      intentionally into the esophagus with the help of a laryngoscope. The Colibri
      worked well in all groups investigated and showed no false results in the group
      with tubes inserted into the trachea and esophagus. Data suggest that the Colibri
      might serve as a valuable tool for evaluating and controlling tube position. This
      device is independent of power supply or electronic equipment, portable, small,
      and immediately ready for use.

PMID- 14724871
TI  - Low risk of infection in selected human bites treated without antibiotics.
AB  - To assess the need for antibiotics in low-risk human bite wounds, a prospective,
      double-blind, placebo-controlled study involving 127 patients presenting with low
      risk human bite wounds over 2 years to a 40,000 visit per year major academic ED
      was performed. Low-risk bites penetrated only the epidermis and did not involve
      hands, feet, skin, overlying joints, or cartilaginous structures. Exclusion
      criteria included age less than 18 years, puncture wounds, immunocompromise,
      allergy to penicillin or related compound, or bites greater than 24 hours old.
      Patients were randomly assigned to receive either a cephalexin/penicillin
      combination or placebo. One hundred twenty-five patients completed the study.
      Infection developed in 1 of 62 patients receiving placebo (1.6%, 95% confidence
      interval CI, 0-7.3%). Infection developed in 0 of 63 patients receiving the
      cephalexin/penicillin combination (0%, 95% CI, 0-4.6%). Antibiotic treatment of
      some low-risk human bite wound could be unnecessary. Infection rates appear
      similar in low-risk human bite wounds whether treated with antibiotics or
      placebo.

PMID- 14724872
TI  - The evolution of thrombolytic therapy and adjunctive antithrombotic regimens in
      acute ST-segment elevation myocardial infarction.
AB  - Acute ST-segment elevation myocardial infarction continues to be associated with
      substantial mortality rates. Despite much advancement in care, current treatments
      have also failed to eliminate the significant risk of morbidity, including
      reinfarction, reocclusion of the infarct-related artery, and thromboembolic
      stroke. The potential benefit of early thrombolytic therapy in reducing mortality
      was first established in 1986. Further benefits of conjunctive therapy with
      aspirin were demonstrated soon thereafter. This review examines the most
      significant trends in the pharmacologic therapy of ST-segment elevation
      myocardial infarction since the publication of these early studies: the
      development of fibrinolytic drugs with improved clot selectivity and improved
      pharmacokinetic profiles that simplify administration, making ED or even
      prehospital thrombolysis more practical. More recent data can be interpreted as
      showing that regimens that are simpler and easier to administer are also
      clinically superior. This article reviews pharmacologic advances and evaluates
      the evidence for their use in EDs.

PMID- 14724873
TI  - Laryngeal mask airway control versus endotracheal intubation by medical personnel
      wearing protective gear.
AB  - The purpose of this study was to evaluate the rates of successful airway control
      using endotracheal tubes (ETs) or laryngeal mask airways (LMAs) and compare them
      between anesthetists and non-anesthetists wearing full antichemical protective
      gear. Anesthetists and non-anesthetists (n = 10 per group) twice attempted
      inserting ETs and LMAs on a mannequin model of airway management in a crossover,
      prospective manner. Times to successful insertion and failure rates were
      recorded. Non-anesthetists had a slightly higher failure rate inserting ETs
      compared with anesthetists (P = not significant). Respective mean times to
      successfully inserting ETs were 38 +/- 7.1 and 26.4 +/- 7.5 seconds (P < .05).
      Both groups inserted LMAs more rapidly than ETs (P < .05) and their failure rates
      in ET use were higher. In view of the relative rapidity by which LMAs were
      inserted as compared with ETs, by fully protected caregivers, the incorporation
      of LMA in algorithms dealing with emergency airway management in a
      nonconventional mass casualty scenario deserves further evaluation.

PMID- 14724874
TI  - Unexpected cardiovascular deaths are rare with therapeutic doses of droperidol.
AB  - In December 2001, the FDA required a "black box warning" suggesting that
      unexpected cardiovascular deaths could occur at normal therapeutic doses of
      droperidol. We reviewed data from 270 MedWatch reports, including 99 reports of
      death, submitted between November 1, 1997, and January 10, 2002. We further
      reviewed primary reports of deaths and cardiovascular adverse events associated
      with < or = 10 mg of droperidol. There were 99 death reports representing 89
      patients, with a specified dose in 66 cases. Among 74 (83%) foreign fatality
      reports, 57 included a known dose (> or = 50 mg in 29 cases [49%] and < or = 2.5
      mg in only 3 cases [5%]). Of the 15 (17%) U.S. cases, 9 included a specified dose
      (< or = 2.5 mg in 5 cases and 5-10 mg in 4 cases). Cardiovascular deaths after
      therapeutic doses (< or = 2.5 mg) of droperidol are rare. Mandatory
      electrocardiographic screening appears unnecessary.

PMID- 14724875
TI  - Levalbuterol compared with racemic albuterol in the treatment of acute asthma:
      results of a pilot study.
AB  - This was a prospective, open-label, nonrandomized pilot study to evaluate
      efficacy and tolerability of levalbuterol (LEV) in acute asthma. Asthmatics
      (forced expiratory volume in 1 second [FEV1], 20-55% predicted) were sequentially
      enrolled into cohorts of 12 to 14 and received 0.63, 1.25, 2.5, 3.75, or 5.0 mg
      LEV or 2.5 or 5.0 mg racemic albuterol (RAC) every 20 minutes x 3. After the
      first dose, FEV1 changes were 56% (0.6 L) for 1.25 mg LEV and 6% (0.07 L) and 14%
      (0.21 L) for 2.5 and 5 mg RAC respectively. After three doses, FEV1 changes were
      74% (0.9 L), 39% (0.5 L), and 37% (0.6 L) for 1.25 mg, LEV 2.5 mg, RAC and 0.63
      mg LEV respectively. LEV doses greater than 1.25 mg did not further improve
      bronchodilation. Baseline plasma (S)-albuterol levels were negatively correlated
      with baseline FEV1 (R = - 0.3, P = .004) and percent change in FEV1 (R = -0.3, P
      = .006). LEV at a dose of 1.25 mg produced effective bronchodilation that was
      greater than both RAC doses. The negative correlation between (S)-albuterol
      levels and FEV1 could suggest a deleterious effect of (S)-albuterol. Larger
      comparative studies are warranted.

PMID- 14724876
TI  - New needle cricothyroidotomy setup.
AB  - We propose a simple and flexible connection setup for needle cricothyroidotomy.
      Needle cricothyroidotomy is a life-saving procedure. It is technically easy to
      perform, but it cannot provide adequate ventilation for a long period of time.
      The standard recommended ventilation equipment for needle cricothyroidotomy
      consists of a jet insuflator connected to a source of oxygen with 50 psi
      pressure. Such a setup is not always available in emergency situations.
      Alternative setups using ventilation with a bag-valve had been proposed. All of
      them are either too bulky or rigid, which increase the chance of
      cricothyroidotomy catheter dislodgment. Connection proposed by us is flexible,
      readily available, and easy to set up.

PMID- 14724877
TI  - Resuscitation of the morbidly obese patient.
AB  - Obesity is a major health care problem in the United States. The body mass index
      (BMI) is the standard measure of obesity. A BMI >25 kg/m2 is defined as
      overweight and obesity as a BMI > 30 kg/m2. Recent surveys indicate that 54% of
      adults, or roughly 97 million people, are overweight. Given the incidence of
      obesity in the general population, it is likely that EM physicians will be
      involved in the emergency care of critically ill or injured obese patients. The
      objective of this article is to present the clinical problems associated with the
      resuscitation of the critically ill or injured obese patient and their potential
      solutions.

PMID- 14724878
TI  - Inguinal hernias: room for a better understanding.
AB  - Inguinal hernias are a common problem but often present with diagnostic dilemmas,
      in part as a result of the complex anatomy of the region. A simplified analogy is
      put forward in the hope of increasing the understanding of the anatomy and some
      guidance given in an endeavor to differentiate direct and indirect hernias, with
      significance to their possible complication rates.

PMID- 14724879
TI  - Pain management in the ED.
AB  - Recent regulatory and legal scrutiny has raised concerns about the over- and
      undertreatment of pain in the hospital. This debate stems from either the overly
      aggressive approach to the management of pain with opioids or, alternatively, to
      the barriers preventing the appropriate prescribing of these medications. The
      media attention on diversion of controlled substances for illicit purposes has
      intensified this debate, highlighting the possible overuse of these medications
      in the treatment of nonmalignant pain. Because pain is a highly common presenting
      complaint in the ED, EPs are pivotal players in these controversies. Accordingly,
      they must apprise themselves of pain management skills and continue to help those
      in need of appropriate medications while thwarting inappropriate prescribing.
      This review offers a synopsis of the pitfalls associated with ED pain management
      and provides recommendations for selected conditions.

PMID- 14724880
TI  - Medical student attitudes toward life-saving clinical skills.

PMID- 14724881
TI  - EM in the 'black forest': Nagorno Karabagh.

PMID- 14724882
TI  - Acute septic sacroiliitis in an injection drug user.

PMID- 14724883
TI  - Scrubs versus professional attire: ED patients are indifferent.

PMID- 14724884
TI  - Pseudoinfarction pattern by misplacement of electrocardiographic precordial
      leads.

PMID- 14724885
TI  - Suffocation caused by large vocal cord polyps.

PMID- 14724889
TI  - Insomnia, biological clock, and the bedtime decision: an economic perspective.
AB  - While insomnia can be a symptom of numerous mental and physical illnesses, it is
      frequently diagnosed as a sleep disorder in its own right, caused mainly by
      stressful life events or by non-synchronization of individuals' biological sleep
      wake cycle with the one they choose to practice. Because of irregular work
      schedules, late-night entertainment, or rapid crossing of several time zones,
      individuals might retire to bed earlier or later than their biological bedtime,
      experiencing difficulties in falling asleep. The present paper develops a simple
      economic model of the bedtime decision, viewing the individual as a rational
      decision-maker who determines her insomnia level through consciously weighing the
      cost and benefit of deviating from her biological bedtime. The model is then used
      to examine the individual's response to stress, yielding a prediction which is
      consistent with observed behavior, although not with sleep therapists'
      recommendations. Finally, the model is applied to the case of transmeridian
      flights, explaining jet lag as a rational adjustment to a misalignment between
      the individual's slow-to-adapt internal clock and her external environment.

PMID- 14724890
TI  - Cost-effectiveness analysis based on the number-needed-to-treat: common sense or
      non-sense?
AB  - This paper explores and critically discusses some of the methodological
      limitations of using the number-needed-to-treat (NNT) in economic evaluation. We
      argue that NNT may be a straightforward measure of benefit when the effect of an
      intervention is immediate, but that serious problems arise when the effect is
      delay rather than avoidance of an adverse event. In this case, NNT is not a
      robust or accurate measure of effect, but will vary considerably and
      inconsistently over time. This weakness will naturally spill over onto any CEA
      based on NNT. A literature review demonstrated that CEAs based on NNT were all
      published within the last five years, and that all studies suffered from
      important limitations. A major weakness of using NNT is the imposed restrictions
      on the outcome measure, which can only be strictly uni-dimensional and non
      generic. Using NNT in economic evaluations is obtained at a cost in terms of both
      methodological shortcomings, and a reduced ability for such evaluations to serve
      as a useful tool in decision making processes. The use of NNT in economic
      evaluations might be better avoided. To every complicated question, there is a
      simple, straightforward, easy--and probably wrong answer (Occam's Sledgehammer).

PMID- 14724891
TI  - Cost-effectiveness analysis and health care resource allocation: decision rules
      under variable returns to scale.
AB  - We argue that health programs are administered in settings that often violate the
      frequently stated assumption of constant returns to scale in the provision of
      health services. Three types of returns to scale are identified from the general
      economic literature: returns to scale with respect to population, effectiveness,
      and quality. We show that decision rules based on incremental cost-effectiveness
      ratios or cost-benefit tests are not optimal if returns to scale are not
      constant. We derive the optimal decision rules under variable returns to scale
      using optimization techniques, and employ several examples to illustrate the
      concepts and methods.

PMID- 14724892
TI  - Responses to standard gambles: are preferences 'well constructed'?
AB  - Standard gamble (SG) is commonly used to elicit preferences in order to assess
      health related quality of life. There has been little qualitative research
      exploring how respondents answer such questions. An SG study was designed to
      elicit values for the health states associated with anti-hypertensive medication,
      stroke and cardiovascular disease. This paper describes a qualitative study that
      was carried out alongside the SG exercise in order to document the thought
      processes respondents bring to bear in formulating their responses. Data were
      generated using 'think aloud' techniques and semi-structured interviews. Values
      were generally well-constructed: responses were thoroughly considered, and
      respondents made complex trade-offs and arrived at a point of indifference.
      However, some respondents incorporated inappropriate information into their
      choices, redefining the hypothetical 'Option B' resulting in problems
      interpreting the probabilistic information. Consideration of non-health factors
      was commonplace, in particular the impact of choices on others. We discuss these
      findings in terms of the use of qualitative methods in health economics and the
      wider discourse surrounding the theoretical underpinnings of health state
      valuation.

PMID- 14724893
TI  - The effects of higher cigarette prices on tar and nicotine consumption in a
      cohort of adult smokers.
AB  - The objective of this paper is to estimate the demand for tar and nicotine in
      cigarettes as a function of cigarette prices in a cohort of cigarette 11,966
      smokers followed for 5 years. Data for the analysis come from a longitudinal
      telephone survey of 11,966 smokers who were interviewed in 1988 and 1993 as part
      of the Community Intervention Trial for Smoking Cessation (COMMIT). Separate
      models are estimated for three age groups to account for differences in levels of
      addiction and brand loyalty across age. We found that smokers respond to higher
      cigarette prices by reducing the number of cigarettes smoked per day but also by
      switching to cigarettes that are higher in tar and nicotine per cigarette.

PMID- 14724894
TI  - The value of risk-free cigarettes--do smokers underestimate the risk?
AB  - The health risk of smoking is valued using the contingent valuation method,
      applied to a Swedish sample of smokers. The respondents were asked to put a value
      on newly developed cigarettes with no associated health risks. The average
      additional willingness to pay for the new cigarettes is estimated to be between
      10 and 41 SEK per pack, where the variation is due to statistical method,
      discounting, and whether the open-ended or closed-ended question format is used.
      Using medical data on life shortening effects of smoking, the results indicate
      rather low values put on a lost life-year, compared to most existing estimates
      based on other methods. This may indicate that smokers do underestimate the
      health risk of smoking. There is also initial optimism-bias regarding people's
      own ability to quit smoking at will. However, there are remaining methodological
      questions and we found little or no sensitivity to scope.

PMID- 14724895
TI  - Increasing patient choice in primary care: the management of minor ailments.
AB  - We examine the effects of an intervention to provide easier access to pharmacists
      for patients with minor ailments. The intervention allowed pharmacists to
      prescribe and dispense medicines currently limited to general practitioners (GPs)
      without patients losing their right to free prescriptions. We show that the total
      number of GP consultations was unaffected by the intervention but that the
      proportion which were for minor ailments decreased. We also use estimate
      multinomial models of patient choices between GP and pharmacies and find that the
      main determinant is the type of minor ailment. Distance appears to have no effect
      on patient choice.

PMID- 14724896
TI  - Simulation of a Hirschman-Herfindahl index without complete market share
      information.
AB  - This paper utilizes maximum likelihood methods to simulate a Hirschman-Herfindahl
      index (HHI) for markets in which complete market share information is unavailable
      or delayed. Many jurisdictions either may be unable to administratively collect
      data or experience delays in collection that make data regarding turbulent
      markets of limited use. With the development of this method, regulatory
      authorities monitoring health-care competition or health-care firms can now use
      market surveys--in which reliable recall is often limited to the largest three or
      four firms--to produce an on-the-spot measure of market concentration.

PMID- 14724900
TI  - The expression of key cell cycle markers and presence of human papillomavirus in
      squamous cell carcinoma of the tonsil.
AB  - BACKGROUND: Chemical carcinogens induce squamous cell carcinoma (SCC) of the head
      and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human
      papillomavirus (HPV) might have an etiologic role in these cancers at particular
      sites. Few studies have compared cell cycle protein expression in HPV-positive
      and HPV-negative tumors in this region. METHODS: Fifty tonsil SCCs were analyzed
      for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16(INK4A),
      p21(CIP1/WAF1), p27(KIP1), and cyclinD1) by immunohistochemistry. RESULTS: HPV
      was present in 42%; almost all were type 16. There were statistical associations
      between HPV positivity and reduced expression of pRb and cyclinD1, overexpression
      of p16, and younger patient age. Tumor with down-regulated p27 tended to have
      down-regulated pRb and p21. CONCLUSIONS: HPV-positive tonsil SCCs have distinct
      molecular pathways. Their association with younger patient age suggests that they
      are biologically distinct from HPV-negative tumors.

PMID- 14724901
TI  - Genetic abnormalities associated with nodal metastasis in head and neck cancer.
AB  - BACKGROUND: Lymphatic metastasis represents the single most important clinical
      prognostic factor in head and neck squamous cell carcinoma (HNSCC), but
      underlying genetic mechanisms remain ill defined. Genetic differences between
      primary carcinomas and their corresponding metastases might form a key to
      understanding the metastatic phenotype. In this study we aimed to characterize
      such differences using a genome-wide screening measure. METHODS: Four human cell
      lines (MDA-686tu, MDA-686Ln, MDA-1386tu, MDA-1386Ln) derived from primary tumor
      and synchronous lymph node metastasis of two cases of metastatic HNSCC were
      subjected to comparative genomic hybridization (CGH) by differentially labeling
      DNA from tumor tissue and normal tissue with fluorescent agents. The labeled DNAs
      were simultaneously hybridized onto normal metaphase chromosomes. In addition,
      modified CGH was performed by directly hybridizing labeled primary tumor DNA
      against differentially labeled metastatic tumor DNA, allowing the direct
      detection of copy number differences in individual pairs. Image analysis for
      fluorescence intensity along the entire length of each metaphase chromosome
      allowed generation of a color ratio, which was used to detect copy number
      changes. RESULTS: In both cases, significant overlap was found between
      chromosomal aberrations present in the primary tumor and the corresponding nodal
      metastasis. However, several abnormalities differentiated primary tumors from
      their metastases. Modified CGH identified several genetic aberrations that were
      not detectable with the conventional CGH analysis. Gains at chromosomes 10p11-12
      and 11p and deletions at chromosomes 4q22-31, 9p13-24, and 14q differentiated
      nodal metastases from the corresponding primary tumors in both cases.
      CONCLUSIONS: The combination of conventional and modified CGH analyses
      facilitates the identification of DNA copy number changes that might be involved
      in the development of a metastatic phenotype. Future research should aim at the
      identification of the genes involved at the identified sites of chromosomal
      aberration.

PMID- 14724902
TI  - Sentinel lymph node biopsy in oral cavity squamous cell carcinoma without
      clinically evident metastasis.
AB  - BACKGROUND: The clinically N0 neck in patients with oral SCC is commonly treated
      by neck dissection because the existence of metastases cannot be excluded. To
      determine whether unnecessary treatment could be avoided, we evaluated the
      feasibility of sentinel lymph node (SLN) biopsy. METHODS: Fifteen previously
      untreated patients with T1 or T2 oral SCC without clinically or radiologically
      detectable metastasis were included. A blue dye and gamma probe were used to
      identify SLNs. SLNs were stained with cytokeratins. All nodes in neck dissection
      specimens were stained using H and E. RESULTS: SLNs were identified in 14
      patients by lymphoscintigraphy and in all patients when probe and dye were
      combined. Four neck dissection specimens contained four metastatic lymph nodes.
      Three of the four lymph nodes were SLN. One SLN was found to be metastatic after
      immunostaining. However, although there was one blue sentinel node in one neck, a
      metastatic non-SLN was present. CONCLUSIONS: Our results show that SLN biopsy is
      a promising tool for use in patients with oral SCC. However, further studies are
      necessary.

PMID- 14724903
TI  - Prognostic significance of p53 expression in oral squamous cell carcinoma without
      neck node metastases.
AB  - BACKGROUND: Aberrations of the p53 gene and overexpression of its protein are
      widely recognized markers of malignancy including oral squamous cell carcinomas.
      This study was performed to evaluate the relationship of immunoexpression of p53
      protein in series of 91 squamous cell carcinomas of the oral cavity with
      clinicopathologic parameters and to investigate whether p53 immunoexpression
      might influence the clinical outcome of the disease. METHODS: From a group of 287
      consecutive patients, 91 surgically treated ones were randomly selected. P53
      protein expression was investigated by means of immunohistochemistry. Clinical
      and histopathologic data were gathered, and the patient survival was analyzed.
      RESULTS: Of the oral carcinomas, 52.7% (n = 48) overexpressed p53, using a
      threshold of 10% stained cell nuclei. There was a negative correlation of p53
      immunoexpression with a histologic grade of differentiation (r = -0.236, p =.06)
      but not with clinical variables. Overall survival rate was 59% at 5 years. In
      univariate analysis, tumor size, node status, and advanced clinical stage were
      significantly associated with shortened overall survival. In patients without
      neck node metastases, p53 showed a strong correlation with survival (p =.01). In
      multivariate analysis performed only on N0 patients, tumor extension and p53
      immunoexpression were found to be the only independent prognostic parameters with
      relative risks of 1.9 and 4.3, respectively. CONCLUSIONS: A strong relationship
      was observed between p53 immunoexpression and poor prognosis in patients with
      oral squamous cell carcinomas without neck node metastases.

PMID- 14724904
TI  - Cancer of the oral cavity: a comparison between institutions in a developing and
      a developed nation.
AB  - BACKGROUND: The literature suggests that the natural history of squamous cell
      carcinoma of the oral cavity may vary and the prognosis is different in patients
      from developing and developed nations. The objective of this study was to compare
      the clinical presentation, management, and outcome of patients with oral cancer
      treated at tertiary care cancer institutions in a developing nation (Brazil-
      Centro de Tratamento e Pesquisa Hospital do Cancer A. C. Camargo [HCACC]) with
      those from a developed nation (United States- Memorial Sloan-Kettering Cancer
      Center [MSKCC]). METHODS: Between January 1990 and December 1994, 602 patients
      underwent initial treatment in the study institutions. RESULTS: Overall, patients
      from HCACC had a higher predominance of men (78.8% vs 54.6%; p <.001) and a
      higher prevalence of tobacco (88.1% vs 77.8%; p =.002) and alcohol consumption
      (80.9% vs 69.8%; p =.004). More patients at HCACC had advanced disease (stage
      III/IV; 73.4% vs 37.4%; p<.001). Even though the overall outcome was poorer in
      patients from HCACC (p <.001), after controlling for stage, there was not a
      statistically significant difference in disease-free or overall survival between
      the two institutions. Only at cancer-specific survival for early-stage disease
      (stage I/II) patients showed a difference (p =.05). Moreover, clinical stage (RR,
      3.7; 95% CI, 2.6-5.5) and definitive treatment (RR, 3.3; 95% CI, 2.4-4.6) were
      the only factors that remained as significant predictors of outcome on
      multivariate analysis. Finally, the rate of subsequent second primary cancers was
      higher in patients from HCACC (p =.03). CONCLUSIONS: Statistically significant
      differences were found in clinical presentation, tumor characteristics, and
      outcome in OC patients between the two institutions from a developing and
      developed nation. Overall outcome was poorer in HACC patients. However, after
      controlling for site, stage, and treatment, the outcome of these patients was
      similar, with the exception of a higher rate of occurrence of second primary
      cancers in patients from HACC. Given that the use of standard protocols of
      treatment offer similar outcomes, the establishment of education programs and
      screening measures for early diagnosis might be the best chance to improve
      overall outcome in OC patients in developing nations.

PMID- 14724905
TI  - Botulinum toxin type A for the treatment of chronic neck pain after neck
      dissection.
AB  - BACKGROUND: Neck dissection surgery is often followed by chronic head and neck
      pain. To date optimal treatment of this type of pain is lacking. Botulinum toxin
      type A (BTX-A) has been shown to be effective in the treatment of myofascial pain
      syndrome and headache. In a pilot study, we wanted to test the effectiveness of
      BTX-A for the treatment of chronic neck pain after neck dissection. METHODS:
      Sixteen patients with chronic neck pain after neck dissection were included in
      this prospective, open study. Eighty to 320 units of BTX-A (Dysport) were
      injected into muscular trigger points. Outcome measures included chronic pain and
      shooting pain on the basis of visual analog scales and quality of life
      improvement (EORTC QLQ-C-30; EORTC QLQ-H and N35) before and 4 weeks after
      treatment. RESULTS: Patients showed a significant reduction in chronic pain (4.5
      before to 3.3 after treatment, p =,005) and in shooting pain (6.1 before to 4.7
      after treatment, p =.005). There was a trend toward improvement in global quality
      of life (QLQ-C30, p =.097) and an increase on the functional scale "pain" (QLQ-H
      and N35, p =.071). CONCLUSIONS: BTX-A treatment of subjects with chronic neck
      pain after neck dissection resulted in a fast and significant reduction of pain.
      A significant improvement in quality of life may be expected in a longer time
      course after treatment.

PMID- 14724906
TI  - Enhancing the outcome of free latissimus dorsi muscle flap reconstruction of
      scalp defects.
AB  - BACKGROUND: Reconstruction of scalp and calvarial defects after tumor ablation
      frequently requires prosthetic cranioplasty and cutaneous coverage. Furthermore,
      patients often have advanced disease and receive perioperative radiotherapy. We
      evaluated the complications of scalp reconstruction with a free latissimus dorsi
      muscle flap in this setting. METHODS: The complications and the oncologic and
      aesthetic outcomes of six consecutive scalp reconstructions with a free
      latissimus dorsi muscle flap and skin graft in five patients with advanced cancer
      were retrospectively evaluated. Patient, tumor, defect, reconstructive, and other
      treatment characteristics were reviewed. Reconstructive and perioperative
      techniques intended to improve flap survival and aesthetic outcome and reduce
      complications in these patients. RESULTS: All patients (52-76 years old) had
      recurrent tumors (sarcoma, melanoma, or squamous cell carcinoma) and received
      postoperative radiotherapy. The mean scalp defect size was 367 cm(2), and partial
      thickness or full-thickness calvarial resection was required in all six cases. No
      vein grafts were needed. The mean follow-up period and disease-free survival time
      were 18 and 13 months, respectively. Three patients died of their disease, and
      two survived disease free. There were no flap failures or dehiscences.
      Complications consisted of donor site seroma in two patients; partial skin graft
      loss in one patient; and radiation burns to the flap, face, and ears in one
      patient. Scalp contour and aesthetic outcome were very good in all cases except
      for the one case with radiation burns. CONCLUSIONS: Good outcomes were achieved
      using a free latissimus dorsi muscle flap with a skin graft for flap
      reconstruction in elderly patients with advanced recurrent cancers who received
      perioperative radiotherapy. Several technical aspects of the reconstruction
      technique intended to enhance the functional and aesthetic outcome and/or reduce
      complications were believed to have contributed to the good results.

PMID- 14724907
TI  - Longitudinal health-related quality of life after mandibular resection for oral
      cancer: a comparison between rim and segment.
AB  - BACKGROUND: Mandibular resection for oral cancer is often necessary to achieve an
      adequate margin of tumor clearance. Segmental mandibulectomy has been associated
      with a poor health-related quality of life (HRQOL), particularly before composite
      free tissue transfer to reconstruct the defect. Little is published in the
      literature contrasting the subjective deficit of segmental compared with rim
      resection. The aim of this study was to use a validated head and neck HRQOL
      questionnaire to compare rim and segmental mandibular resection in patients
      having primary surgery for oral cancer. METHOD: There were 224 consecutive
      patients between 1995 and 1999 who were treated by primary surgery for oral
      squamous cell carcinoma. One hundred twenty-tree had no mandibular resection, 44
      had a rim resection, and 57 had a segmental resection. The University of
      Washington Quality of life questionnaire (UW-QOL) was administered before
      treatment, at 6 months, 12 months and after 18 months. RESULTS: Preoperatively,
      patients undergoing segmental resection reported significantly more pain, chewing
      problems, and a lower composite UW-QOL score. Postoperatively, the segment group
      tended to score worse at all time points, particularly in appearance, swallowing,
      recreation, and chewing; however, the difference between rim and segment was only
      seen in smaller resections without adjuvant radiotherapy. Little difference was
      seen between rim or segment for tumors < 4 cm with radiotherapy and between rim
      and segments for tumors > 4 cm. CONCLUSION: After segmental mandibulectomy and
      reconstruction using composite free tissue transfer, the UW-QOL scores were
      relatively good. The only 2 difference between rim and segments was noted in the
      small resections without radiotherapy, and some of this was reflected in
      differences at baseline.

PMID- 14724908
TI  - Polymorphisms of GSTT1 and related genes in head and neck cancer risk.
AB  - BACKGROUND: Glutathione S-transferase T1 detoxifies some environmental
      carcinogens while activating others and is deleted in 15% to 38% of humans. We
      sought to determine whether GSTT1 genotype and genotypes of several related genes
      are associated with risk of squamous cell carcinoma of the head and neck (HNSCC).
      METHODS: Somatic genotypes for GSTT1, GSTM1, GSTP1, and CYP1A1 were determined in
      283 individuals with HNSCC and 208 population-based controls. RESULTS: The OR for
      presence of GSTT1 was 1.6 (CI, 1.1-2.5, p = 0.03). HNSCC risk was not associated
      with GSTM1 null genotype, the presence of the GSTP1 Val/Val genotype, or the
      Val/Val homozygous genotype for CYP1A1. Stratified analysis revealed disparate
      ORs for women (OR, 3.0; CI, 1.5-6.3) and men (OR, 1.2; CI, 0.7-2.1) for the
      presence of GSTT1. CONCLUSIONS: In this population, the presence of GSTT1 gene
      was associated with a significant increase in the risk of HNSCC. This association
      was particularly robust in women.

PMID- 14724909
TI  - Clinical outcomes for the elderly patient receiving a tracheotomy.
AB  - BACKGROUND: Tracheotomies are routinely performed for severely ill and elderly
      patients with respiratory failure. This intervention is questioned, given the
      poor survival rate in this group. Outcomes analysis is performed after
      tracheotomy. METHODS: This is a retrospective study of 78 elderly patients, who
      received tracheotomies for respiratory failure. Pretracheotomy data (age, length
      of oral intubation, and DNR status) were collected. Outcomes analyzed during the
      same admission as the tracheotomy included death versus discharge, ventilator
      dependence, vocal function, route of feeding, decannulation, and ICU discharge
      disposition. RESULTS: The mean age was 77.6 +/- 11 years (median, 79 years) and
      patients were intubated for 16.7 +/- 9 days. Forty-two percent (n = 33) obtained
      DNR orders after tracheotomy, and 8% (n = 6) before tracheotomy. Seventy-one
      percent of patients (n = 55) had gastrostomy tubes placed. Fifty-six percent of
      patients (n = 44) died after tracheotomy; median time from tracheotomy to death
      was 31 days. After tracheotomy, 53 % (n = 41) remained at least partially
      ventilator dependent, 18 % (n = 14) regained consistent vocal function, and 13 %
      (n = 10) were decannulated. For those who died, 27 % (n = 12) died without
      leaving the ICU. CONCLUSION: These data demonstrate that a large proportion of
      elderly, severely ill patients with respiratory failure suffer poor outcomes
      after tracheotomy. More stringent criteria are necessary for performing the
      tracheotomy in this patient population.

PMID- 14724910
TI  - Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and
      radiochemotherapy. Part 2: diagnosis and management of mucositis.
AB  - BACKGROUND: Oral mucositis is a common sequel of radiotherapy, chemotherapy, and
      radiochemotherapy in patients with cancer or patients requiring hemopoietic stem
      cell transplants. Mucositis has a direct and significant impact on the duration
      of disease remission and cure rates, because it is a treatment-limiting toxicity.
      Mucositis also affects survival because of the risk of infection and has a
      significant impact on quality of life and cost of care. METHODS: This article
      reviews publications on the diagnosis and management of oral mucositis accessible
      from a MEDLINE search using as key words mucositis, radiotherapy, chemotherapy,
      hemopoietic stem cell transplant, and oral. CONCLUSIONS: Conventional care of
      patients with mucositis is currently essentially palliative, with good oral
      hygiene, narcotic analgesics, and topical palliative mouth rinses.

PMID- 14724911
TI  - Acinic cell carcinoma of the parotid gland presenting as an external auditory
      canal mass.
AB  - BACKGROUND: The fissures of Santorini have long been known as a gateway for
      disease to pass from the external auditory canal to the periparotid and neck
      spaces. Although anatomically understandable, description of disease that
      originates in the parotid gland and extends through the fissures to the external
      auditory canal is rare. This is, in fact,the first presentation of such a patient
      at our institution in a previously untreated patient. METHODS: A 43-year-old
      woman was seen with a mass in her right external auditory canal. Further
      evaluation found this to be the presenting finding of a parotid neoplasm. The
      patient also had a right marginal mandibular paresis. Biopsy of the external
      auditory canal mass provided a diagnosis of an acinic cell adenocarcinoma. She
      underwent a right lateral temporal bone resection, type III modified neck
      dissection, and radical parotidectomy with facial nerve sacrifice and rectus
      abdominus reconstruction with facial nerve grafting. RESULTS: Pathologic
      examination of the specimen revealed an acinic cell carcinoma of the right
      parotid gland with focal dedifferentiation into a high-grade adenocarcinoma.
      CONCLUSIONS: Care should be taken with auditory canal masses to remember the
      possibility that disease is extending from the parotid through the fissures of
      Santorini, and evaluation and management should proceed accordingly.

PMID- 14724912
TI  - Sinonasal neuroendocrine carcinoma in association with SIADH.
AB  - BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare malignancy of the nasal
      cavity or paranasal sinuses. The syndrome of inappropriate ADH secretion (SIADH)
      has not been previously reported in association with this cancer. METHODS: We
      report a 30-year-old woman with histologically confirmed neuroendocrine carcinoma
      who also demonstrated SIADH. After successful chemotherapy and radiotherapy
      treatment for the neoplasm, her SIADH resolved. A literature search found eight
      cases of olfactory neuroblastoma (ONB) associated with SIADH, four of which
      resolved after treatment of the malignancy. RESULTS: Treatment of the underlying
      malignancy resulted in the immediate resolution of the SIADH. CONCLUSIONS: We
      report the first case of SIADH associated with NEC, which resolved after
      treatment of the cancer. A direct cause and effect between ONB/nasal NEC and
      SIADH has been established in previous reports.

PMID- 14724913
TI  - Diagnosis and treatment of supraglottic laryngeal paraganglioma: report of a
      case.
AB  - BACKGROUND: Paragangliomas of the larynx are unusual tumors that are seen as a
      vascular submucosal mass. These usually are seen in the supraglottic larynx but
      have also been found in the subglottis. This is the only laryngeal neuroendocrine
      tumor with a female predilection. It is important that paragangliomas be
      differentiated from other neuroendocrine tumors of the larynx, including atypical
      carcinoid, because of differing treatment modalities. METHODS: We present the
      clinical, radiologic, and pathologic findings of a supraglottic laryngeal
      paraganglioma seen in a 50-year-old woman with a 6-month history of slowly
      progressive hoarseness. RESULTS: The tumor was successfully approached by means
      of a midline laryngofissure with mucosal preservation. The patient remains
      disease free 24 months after surgery. CONCLUSIONS: Preoperative CT and
      angiography are useful in making the diagnosis of paraganglioma before surgical
      intervention. Complete excision through an external mucosa-sparing approach is
      the treatment of choice. Distinguishing laryngeal paraganglioma from other
      neuroendocrine tumors can be difficult. Immunohistochemistry is an important tool
      for the correct pathologic diagnosis.

PMID- 14724914
TI  - Franz Boas, geographer, and the problem of disciplinary identity.
AB  - This paper examines Franz Boas as an aspiring professional geographer during the
      1880s: his Baffin Land research, his publications, his participation in geography
      organizations, and his struggle to attain a university appointment in geography.
      Frustrated by a seeming lack of opportunity for advancement in Germany, Boas
      explored career opportunities as a geographer in America and launched a series of
      unsuccessful but meaningful attempts to dominate the intellectual direction of
      American geography. Finally, the article reviews the circumstances surrounding
      Boas's appointment as an anthropologist at Clark University in 1889. Through
      examining Boas's own words and actions, the paper demonstrates that his
      professional identification with geography was lengthier and stronger than
      earlier accounts have suggested. It also critiques the myth of a Baffin Land
      "conversion" to anthropology, and delineates the circumstances of his shift from
      German human geography to his Americanist recasting of anthropology after 1889.

PMID- 14724915
TI  - Culture at work: Family therapy and the culture concept in post-World War II
      America.
AB  - During the 1950s and 1960s, the concept of culture had currency beyond the
      disciplinary boundaries of anthropology and sociology. This article takes up a
      clinical example of the invocation of the culture concept by examining how early
      family therapists such as Nathan Ackerman, Murray Bowen, and Don Jackson used
      culture as a category of analysis during the formative years of their new field.
      The culture concept played an integral role in the processes by which family
      therapists simultaneously defined the object of their research and treatment, the
      family, and built their new field. Their varied uses of culture also contained
      tensions and contradictions, most notably between universal and relativist views
      of family and psychopathology and between views of family therapy as a
      conservative force for maintaining the nuclear family or a progressive force for
      overcoming social inequality.

PMID- 14724917
TI  - Nomothetic science and idiographic history in twentieth-century Americanist
      anthropology.
AB  - For over a century, Americanist anthropologists have argued about whether their
      discipline is a historical one or a scientific one. Proponents of anthropology as
      history have claimed that the lineages of human cultures are made up of unique
      events that cannot be generalized into laws. If no laws can be drawn, then
      anthropology cannot be a science. Proponents of anthropology as science have
      claimed that there indeed are laws that govern humans and their behaviors and
      cultures, and these laws can be discovered. Interestingly, both sides have the
      same narrow view of what science is. The same sorts of debates over science and
      history were played out in evolutionary biology over a half-century ago, and what
      emerged was the view that that discipline and its sister discipline,
      paleontology, were both history and science--hence the term "historical
      sciences." Anthropology and its sister discipline, archaeology, have only
      recently begun to realize that they too are historical sciences.

PMID- 14724921
TI  - Technology in psychotherapy: an introduction.
AB  - All indicators suggest that technology may be an inherent part of psychotherapy
      delivery in the next decade. This article serves as an introduction to a special
      issue of Journal of Clinical Psychology: In Session devoted to technology in
      psychotherapy. Articles in this series feature self-help Internet sites, computer
      administered psychotherapy, adjunctive palmtop computer psychotherapy, virtual
      reality psychotherapy, interactive voice messaging systems, biofeedback via
      ambulatory physiological monitoring, synchronous and asynchronous online support
      groups, and use of electronic mail by psychotherapists. As illustrated by many of
      the articles in this issue, technological advances may extend psychotherapy
      beyond the therapy hour and increase psychotherapy dissemination, client
      motivation, and compliance.

PMID- 14724922
TI  - Computer-aided CBT self-help for anxiety and depressive disorders: experience of
      a London clinic and future directions.
AB  - This article describes a broad-spectrum, computer-aided self-help clinic that
      raised the throughput of anxious/depressed patients per clinician and lowered per
      patient time with a clinician without impairing effectiveness. Many sufferers
      improved by using one of four computer-aided systems of cognitive behavior
      therapy (CBT) self-help for phobia/panic, depression, obsessive-compulsive
      disorder, and general anxiety. The systems are accessible at home, two by phone
      and two by the Web. Initial brief screening by a clinician can be done by phone,
      and if patients get stuck they can obtain brief live advice from a therapist on a
      phone helpline. Such clinician-extender systems offer hope for enhancing the
      convenience and confidentiality of guided self-help, reducing the per-patient
      cost of CBT, and lessening stigma. The case examples illustrate the clinical
      process and outcomes of the computer-aided system.

PMID- 14724923
TI  - Using technical innovations in clinical practice: the Drinker's Check-Up software
      program.
AB  - Interest in assessing and treating a variety of psychological conditions with
      software programs is increasing rapidly. This article reviews a software program
      for problem drinkers entitled the Drinker's Check-Up (DCU) and illustrates its
      use with three patients. The DCU is based on the principles of brief motivational
      interventions and can be used as a stand-alone intervention by therapists without
      expertise in substance abuse or as a prelude to alcohol treatment services. It is
      the first software program to provide integrated assessment, feedback, and
      assistance with decision making for individuals experiencing problems with
      alcohol. Preliminary data from an ongoing clinical trial of the DCU as a stand
      alone intervention indicate that it is an effective intervention for a wide range
      of problem drinkers.

PMID- 14724924
TI  - Internet-based cognitive behavioral therapy for tinnitus.
AB  - Tinnitus is a common otological problem that is often resistant to surgical or
      medical interventions. In common with chronic pain, cognitive-behavioral
      treatment has been found to alleviate the distress and improve the functioning of
      tinnitus patients. Recently, a self-help treatment has been developed for use via
      the Internet. In this article, we describe the self-help program and apply it to
      a middle-aged woman with tinnitus. We report the case formulation, which was done
      in a structured interview, and the treatment interactions, which were conducted
      via e-mail. The self-help program was presented on Web pages, and weekly diaries
      were submitted to follow progress and give feedback. The treatment was successful
      with reductions of tinnitus-related annoyance and anxious and depressive mood.
      Implications for Internet administration of self-help treatment are discussed.

PMID- 14724925
TI  - Palmtop computer-assisted group therapy for social phobia.
AB  - This article describes the application of group computer-assisted therapy for
      social phobia. The computer program includes a diary function for ongoing self
      monitoring of anxiety as well as guidance on the practice of relaxation,
      cognitive restructuring, and self-control desensitization. Although the program
      was originally designed to treat individuals with generalized anxiety disorder
      (GAD), it was hypothesized that the program also would be effective for
      individuals with social phobia; therefore, it was implemented in a group of
      individuals with a primary diagnosis of GAD or social phobia. We present the case
      of a client with social phobia who received six sessions of group therapy and who
      carried the ambulatory computer throughout this treatment. Outcome data suggest
      that the treatment was highly effective for this client as well as others with a
      diagnosis of social phobia or GAD.

PMID- 14724926
TI  - Water-friendly virtual reality pain control during wound care.
AB  - Recent research suggests that entering an immersive virtual environment can serve
      as a powerful nonpharmacologic analgesic for severe burn pain. The present case
      study describes an attempt to use water-friendly virtual reality (VR) technology
      with a burn patient undergoing wound care in a hydrotherapy tub. The patient was
      a 40-year-old male with 19% total body surface area deep flame/flash burns to his
      legs, neck, back, and buttocks. The virtual reality treatment decreased the
      patient's sensory and affective pain ratings and decreased the amount of time
      spent thinking about his pain during wound care. We believe that VR analgesia
      works by drawing attention away from the wound care, leaving less attention
      available to process incoming pain signals. The water-friendly VR helmet
      dramatically increases the number of patients with severe burns that could
      potentially be treated with VR (see http://www.vrpain.com).

PMID- 14724927
TI  - Respiratory feedback for treating panic disorder.
AB  - Panic disorder patients often complain of shortness of breath or other
      respiratory complaints, which has been used as evidence for both hyperventilation
      and false suffocation alarm theories of panic. Training patients to change their
      breathing patterns is a common intervention, but breathing rarely has been
      measured objectively in assessing the patient or monitoring therapy results. We
      report a new breathing training method that makes use of respiratory biofeedback
      to teach individuals to modify four respiratory characteristics: increased
      ventilation (Respiratory Rate x Tidal Volume), breath-to-breath irregularity in
      rate and depth, and chest breathing. As illustrated by a composite case, feedback
      of respiratory rate and end-tidal pCO2 can facilitate voluntary control of
      respiration and reduce symptoms. Respiratory monitoring may provide relevant
      diagnostic, prognostic, and outcome information.

PMID- 14724928
TI  - Computer and Internet applications for psychological treatment: update for
      clinicians.
AB  - Computers and the Internet have the potential to be used to deliver psychological
      treatments. This article provides a selective review of applications involving
      little or no therapist contact, applications involving asynchronous and
      synchronous communication with providers, and applications that have been used as
      adjuncts to standard psychotherapy. Data on the efficacy of these applications
      most strongly support using the Internet to complete and submit behavioral
      assignments, to obtain social support from peers, and to receive education,
      feedback, and support from therapists in the form of e-mail or chatroom
      communications. General practice recommendations are given with an emphasis on
      ways to encourage use of the Internet as an information and communication tool as
      an adjunct to regular psychotherapy.

PMID- 14724929
TI  - Apathetic fallacy.

PMID- 14724930
TI  - [Culture of hairy roots in Pueraria phaseoloides and its puerarin production].
AB  - An efficient transformation system for genetic transformation of medicinal plant,
      Pueraria phaseoloides was developed, by using agropine-type Agrobacterium
      rhizogenes ATCC15834. Hairy roots could be obtained via callus from the cut edges
      of leaf explants of P. phaseoloides 20 days after inoculation with agrobacterium.
      35 days after infection, the percentage of rooted leaf explants was about 85%.
      Hairy roots could have an autonomous growth on solid or liquid growth regulator
      free MS medium but grew more rapidly and formed no callus during culture in
      liquid medium. The transformation of hairy roots was confirmed by PCR
      amplification of rolB and rolC genes of Ri plasmid from A. rhizogenes. To
      investigate the physiological difference between solid and liquid culture, the
      mitochondrial membrane potential in hairy roots cultured for 15 days in solid and
      liquid medium were also detected by the method of fluorescence labeling of 3,3'
      dipropylthiadicarbocyanide iodide. The results showed mitochondrial membrane
      potential of hairy roots in liquid medium was 11.8 times higher than that on
      solid medium. The content of puerarin in hairy roots reached a level of 1.190
      mg/g.dry.wt and was 2.5 times as much as that in the roots of P. phaseoloides
      seedlings and was also 1.067 times as much as that in the crude drug of several
      year-old Pueraria roots. Our experiments have laid a foundation for large-scale
      production of puerarin in P. phaseoloides hairy roots.

PMID- 14724931
TI  - [Ultracytochemical localization of calcium and ATPase activity on the 2,4-D
      induced somatic embryogenesis of Lycium barbarum L].
AB  - In order to research the function mechanism of the 2,4-D during the development
      of plant somatic embryogenesis, we studied its function mechanism and
      relationship with the space-time distributing of Ca2+ content and ATPase activity
      on somatic embryogenesis of Lycium barbarum L. The possible effects on 2,4
      dichlorophenoxyacetic acid (2,4-D) induced somatic embryogenesis and changes of
      Ca2+ and ATPase active at different development period of somatic embryogenesis.
      The result showed: The 2,4-D was a key hormone for induced embryonic state of
      Lycium barbarum L. The embryonic callus and non-embryonic callus was separately
      obtained in the medium that contains the auxin 2,4-D and lack 2,4-D. In the
      present study, we have observed the Ca2+ was more abundant in the further
      intercellular matrix and on the cell wall at the multi-cellular stage, and Ca2+
      was concentrated in the plasma membrane and vacuoles membrane during embryonic
      cell differentiate and division, to the globular embryo, more Ca2+ was seen in
      the nucleus. Afterward, it was also observed to be distributed in the thicken
      cell wall and intercellular matrix. At the same process, the variations of ATPase
      activity and Ca2+ were highly similar, ATPase activity was mainly located on the
      plasma membrane in early embryogenic cells. With further development, it was also
      observed to be distributed in endoplasm, nucleus and vacuoles, with the
      thickening of embryogenic cell wall, ATPase activity was found in the thickened
      region and the intercellular space. However, the variations of ATPase activity
      and Ca2+ have not clearly observed variety dynamics at the nonembryogenic callus,
      and with further vacuolation of nonembryogenic cell, Ca2+ content and ATPase
      activity gradually drop. It was indicated there was a closely relationship
      between the dynamics of Ca2+ and ATPase activity in somatic embryogenesis by 2,4
      D induced. And the space-time distribution of Ca2+ and ATPase activity play a key
      role on signal transmission and the regulation of relevant gene expression.

PMID- 14724932
TI  - [Inhibitory effects on hepatocarcinoma and B16 melanoma cells by N-(4
      hydrophenyl) retinamide].
AB  - In this paper, a significantly effect of N-(4-hydrophenyl) retinamide (4-HPR), a
      derivative of retinoic acid, was observed on inhibition of migration, invasion,
      cell growth, and induction of apoptosis in hepatoma cells and B16 melanoma cells.
      The number of migratory hepatoma cells reduced significantly from the control 201
      +/- 27.2 to 58 +/- 5.03 after 6-hour incubation with 4-HPR (p < 0.01, n = 4). The
      number of migratory B16 melanoma cells reduced from the control 302 +/- 30.1 to
      254 +/- 25.04 (p < 0.05, n = 4). The invasive ability of these cells was also
      suppressed by 4-HPR treatment. Cells that penetrated the artificial membrane
      matrigel decreased from 27 +/- 13.1 to 11.2 +/- 3.3 in hepatoma cells, from 67.5
      +/- 10.1 to 24.3 +/- 3.2 in B16 melanoma cells (p < 0.05, n = 3). Furthermore,
      cell growth was significantly inhibited especially in B16 melanoma cells and
      37.11 +/- 0.94% cells were induced to apoptosis after 48-hour induction by 4-HPR,
      which was significantly higher than those by retinoic acid treatment (p < 0.05).
      Although the mechanism of 4-HPR effects was not very clear, over expression of
      CST, which was inhibited by 4-HPR in our previous study, could diminish the
      apoptosis--inducing effect by 4-HPR. We believe that 4-HPR has a strong
      inhibitory effect on melanoma and hepatocarcinoma cells and might become a potent
      therapeutic agent.

PMID- 14724933
TI  - [Double-antisense ACC oxidase and ACC synthase fusion gene introduced into tomato
      by Agrobacterium-mediated transformation and analysis the ethylene production of
      transgenic plants].
AB  - The tomato fruit-specific promoter 2A11 was amplified from tomato genomic DNA
      using PCR techniques. Total RNA was isolated from ripen fruit of tomato, then ACC
      oxidase gene and ACC synthase gene were obtained using reverse-transcription
      polymerase chain reaction. The fusion encoding ACC oxidase and ACC synthase gene
      was obtained through ACC oxidase gene and ACC synthase gene ligation. The fusion
      gene was then inserted into a plant binary vector pYPX145 in an inverted
      orientation. Finally, the binary plant expression vector pOSACC was constructed
      in which the double-antisense fusion gene was controlled by fruit-specific 2A11
      promoter. By using hypocotyls and cotyledon petioles as explants, the unit of
      double-antisense fusion gene was successfully introduced into tomato
      (Lycopersicon esculentum Mill) cultivar "Hezuo 903" by Agrobacterium tumefaciens
      mediated transformation. 105 transgenic plants were obtained through 200 mg/L
      kanamycin selection and GUS assay. Two lines of DR-1 and DR-2 were obtained
      through selecting the characteristics of prolonged shelf life and agriculture.
      The transgenic plants showed the characteristics of prolonged shelf life over 50
      d. The amount of ethylene released from DR-1 and DR-2 fruits were reduced
      significantly to about 9.5% of that released by non-transformed controls.

PMID- 14724934
TI  - [Biological characterization of immortalized porcine chondrocytes by introduction
      of telomerase].
AB  - The aim of this project was to acquire a clonal immortalized porcine chondrocyte
      cell line and to determine its biological characterization. Porcine auricle
      chondrocytes were infected with a retroviral vector pBABE-hTERT followed by
      selection with 2 micrograms/ml puromycin. RT-PCR and PCR-ELISA performed on
      separated colonies showed a cell line (TL1) with high and stable ectopic
      expression of hTERT. The growth curve, HE staining, flow cytometry, and
      tumorigenicity were analyzed to define the biological characterization of the
      immortalized chondrocytes. TL1 cells showed an increase in cellular viability and
      the reduction in apoptosis. But there was no malignant transformation and tumor
      development in nude mice. The changes of chondrocyte marker expression in this
      cell line revealed that it remained unstable phenotype. So high ectopic
      expression of hTERT is able to extend the life span of chondrocytes, but it
      unable to keep their differentiated phenotype during serial monolayer culture in
      vitro.

PMID- 14724935
TI  - [Lymphatic metastasis and VEGF-C expression in ovarian epithelial tumors].
AB  - The aim of the present study was to explore the role of vascular endothelial
      growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and
      lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and
      immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian
      carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells
      were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive
      vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C
      mRNA and protein expression in ovarian epithelial carcinomas were significantly
      higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p <
      0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3
      positive vessels and MVD were significantly higher in the cases of clinical stage
      III-IV and with lymphatic metastasis than those of clinical stage I-II and
      without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3
      positive vessels and MVD was significantly higher in the VEGF-C protein positive
      tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was
      significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might
      play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in
      epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of
      metastasis in ovarian epithelial carcinomas.

PMID- 14724936
TI  - [Effects of serum from a patient with acute motor axonal neuropathy on spinal
      motor neurons cultured in vitro].
AB  - The effect of serum from a patient with acute motor axonal neuropathy (AMAN) on
      cultured motor neurons was studied. The ventral spinal ventral tissue was
      isolated from embryonic rats and digested into dissociated cell suspension for
      culture in vitro. The cultured cells were stained with SMI-32, a non
      phosphorylated neurofilment marker monoclonal antibody to identify motor neurons.
      The 6 days' cultured cells were exposed to the AMAN patient serum in a
      concentration of 25%, and to the normal human serum as the control. Positive
      PennerO:19 Campylobacter jejuni lipopolysaccharide antibody in the AMAN serum
      used in this experiment had been testified. The serum-cultured motor neurons were
      observed morphologically and also stained by Guillery Shirra and Webster method.
      With this staining, degenerated nerve fibers were brown-black and normal nerve
      fibers were brown-yellow. At the 9th h after the AMAN serum exposure, the axon
      degenerated and was stained brown-black due to increased silver-phile property.
      At the 12th h, the neuron soma began to swell and nuclear deviation with silver
      granules depositing in the cytoplasm. At last, the neurons began to die from the
      16th h of the exposure. However, the control motor neurons did not show these
      alterations in the same period of culture. The serum of AMAN patient may be toxic
      to the neurite of motor neuron and thus cause axon degeneration, then soma
      alterations and death followed. It is suggested that Campylobacter jejuni
      lipopolysaccharide antibody may play an important role in this process without
      the participation of macrophages and complements.

PMID- 14724937
TI  - [Genetic analysis of a rolled-leaf mutant in rice population of T-DNA insertion].
AB  - A rolled-leaf mutant was obtained in a T-DNA(containing bar gene and Ds element)
      insertion population, which consist of transgenic japonica rice Zhonghua 11
      mediated by Agrobacterium tumefaciens. Through self-hybridization of three
      generations, one of trait-purified mutants (R1-A2) was obtained and used as
      parent to cross with variety Zhonghua 11. The leaves of 36 F1 plants investigated
      were rolled and resistant to herbicide Basta. Among 852 F2 plants, the
      segregation ratio of rolled leaves to normal leaves(645:207) was consistent with
      3:1. All rolled-leaf plants were resistant to herbicide Basta, and all normal
      leaf plants were sensitive to herbicide Basta. These results showed that the
      trait of rolled-leaf is co-segregated with Basta resistance. The total DNA of 45
      rolled-leaf plants and 30 normal leaf plants in F2 population were amplified to
      test the presence of T-DNA by Ds primers. The results showed that the positive
      band were amplified in all rolled-leaf plants, but not in every normal leaf
      plant. In F1B1 progenies, all plants which derived from backcross parent R1-A2
      were rolled leaves; while variety Zhonghua 11 was used as backcross parent, the
      segregation ratio of rolled-leaf to normal leaf was consistent with 1:1. Taking
      these data together, it indicated that the rolled-leaf mutant was co-segregation
      with T-DNA and controlled by single dominant gene.

PMID- 14724938
TI  - [Emodin sensitizes HeLa cell to arsenic trioxide induced apoptosis via the
      reactive oxygen species-mediated signaling pathways].
AB  - Since reactive oxygen species(ROS) has been known to play an important role in
      apoptosis induced by arsenic trioxide, we attempt to elevate the cellular ROS
      level on HeLa cell by an natural anthraquinone-emodin, then to study its effect
      on apoptotic sensitivity to arsenic, and finally to investigate the mechanisms of
      the involved signaling pathway. The results showed that emodin 10 micromol/L
      could enhance arsenic induced apoptosis via generation of ROS, whereas rendered
      no detectable effect on normal fibroblast. Increased ROS promoted mitochondrial
      transmembrane potential collapse; inhibited the activation of transcription
      factors NF-kappa B. The study elucidated that emodin sensitize HeLa cells via
      generation of ROS which result in enhancement of apoptosis signaling pathway and
      inhibition of survival signaling pathway.

PMID- 14724939
TI  - [Displaying polyhistidine peptide on the cell surface of Bacillus thuringiensis
      by S-layer protein].
AB  - Cell surface layer (S-layer) is the outmost structure of bacterium cell and
      covers the intact cell. S-layer protein of Bacillus thuringiensis strain CTC (CTC
      protein) was used as carrier protein to display polyhistidine (polyHis) peptides
      on the cell surface. Series fusion protein genes were constructed by inserting
      DNA fragments encoding (6His)1, (6His)2, (6His)3, (6His)9 and (6His)15 polyHis
      peptides into CTC protein gene at the site of downstream of slh domain. With the
      help of recombinant plasmid pBMB-CSA, which contains operon csaAB needed for S
      layer protein anchoring on cell surface, fusion protein genes were expressed in
      crystal negative B. thuringiensis strain 4Q7. SDS-PAGE profiles demonstrated that
      all the fusion proteins except CTC-(6His)15 were expressed. Ni-NTA-agarose beads
      binding test showed that all recombinant strains could attach to agarose beads
      except 4Q7 (pBMB-CSA, pBMB-SH15). Cd2+ adsorption test indicated that the
      adsorption ability of all recombinant strains except 4Q7 (pBMB-CSA, pBMB-SH15)
      were higher than that of host strains. The Cd2+ adsorption quantity of the
      recombinant strain with strongest adsorption ability was twice higher than that
      of host strain.

PMID- 14724940
TI  - p38 MAPK expression pattern during early mouse embryo development.

PMID- 14724941
TI  - [Observation amyloplasts in the gravity-insensitive mutant of rice under gravity
      and microgravity conditions].
AB  - Using histochemistry and optical microscope, we examined the number and the size
      of amyloplasts in specialized tissues of gravitropically receptive organs-tissues
      such as the coleoptile and sheath of rice mutant (insensitive to gravity) and
      wide type (Oryza sativa L. subsp. japonica) (Zhonghua 11). We found there was no
      statistical difference between the mutant and wide type, both of which grew on
      earth or on the clinostat respectively. On earth, it was found that amyloplasts
      sedimented at the distal end of each cell of the special starch sheath tissues
      and re-sedimentation of amyloplasts toward the direction of gravity was almost
      completed in 5 minutes after inverting the seedlings. On the clinostat,
      amyloplasts dispersed in the starch sheath tissue. Such observations indicated
      that the mutation was not resulted from the starch-deficiency or starch-absence,
      the further research is going on.

PMID- 14724942
TI  - [Genetic instability of gene nm23H1 in colon cancer of Chinese patient].
AB  - Techniques such as DNA extraction from paraffin-embedded tissues, polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary
      silver stain, Envision immunohistochemistry and Leica-Qwin computer imaging
      techniques were used to study microsatellite instability (MSI) and loss of
      heterozygosity (LOH) of locus D17S396 at the 17th chromosome of Chinese patients
      and their influence on the expression of gene nm23H1, and to clarify the
      relationship between the genetic instability of gene nm23H1 and the development
      of colon cancer, which may provide experimental basis for clinical treatment. In
      our experiments, the frequency of MSI, LOH and nm23H1 protein reacted positive of
      30 cases of colon cancer were 26.67%, 20.00% and 53.33% respectively. In tumor
      node metastasis (TNM) staging, the positive frequency of MSI (43.75%) and nm23H1
      protein (81.25%) in stage I + II were more than those (MSI 7.14%, p < 0.05 and
      nm23H1 21.43%, p < 0.01) in stage III + IV, while the frequency of LOH (35.71%),
      which had a rising trend along with the Duke's staging increasing, was higher
      than that of LOH (6.25%, p < 0.05) in stage I + II. The positive frequency of
      nm23H1 protein in the group of tubular adenocarcinoma (60.00%) was distinctively
      higher than that in the group of mucoid adenocarcinoma (20.00%, p < 0.01),
      showing a rising trend along with the increase of the differentiation degree of
      tubular adenocarcinoma. Furthermore, the positive frequency of nm23H1 protein in
      MSI positive group was also higher than MSI negative group (p < 0.05). And there
      was no difference in nm23H1 protein expression analyzed by computer imaging
      techniques. The results of experiments indicated that both MSI and LOH controlled
      the development of sporadic colon cancer independently in different paths. LOH
      occurred mostly in the late period of sporadic colon cancer and endowed with it a
      high aggressive and poor prognosis. In contrast, MSI was an early period molecule
      marker of sporadic colon cancer. Increasing the amount of nm23H1 protein
      expression could effectively restrain colon cancer metastasis and improved
      prognosis of sporadic colon cancer patients.

PMID- 14724943
TI  - [The study of pollutant's effects on macrophages and its significance in
      biological monitoring].
AB  - This study aimed to investigate the effects of environmental pollutant sulfite
      and inorganic mercury on the peritoneal macrophages (PM phi) of mice and further
      explore the significance of macrophage as a biomarker in biological monitoring.
      PM phi were taken from the peritoneal cavity of mice and cultivated with Na2SO3
      and HgCl2 respectively in vitro, and then morphologic changes were detected under
      light microscope and electron microscope. Also the function of PM phi was
      detected in yielding nitric oxide (NO), reducing MTT and phagocytizing. After
      affected by the pollutants, marked morphologic changes of PM phi were observed,
      and NO reducing, cell vigor and phagocytizing of PM phi were obviously inhibited
      (p < 0.05 or p < 0.01). And some PM phi were necrotic caused by HgCl2 at high
      concentration(10(-4) mol/L). The results suggested that PM phi of mice was
      damaged distinctly by using Na2SO3 and HgCl2 which showed sulfite and inorganic
      mercury directly impacted on non-special defensive function of macrophages.
      Meanwhile the experiment indicated that macrophage could be used as an effective
      biomarker in biological monitoring of environmental contamination.

PMID- 14724944
TI  - [The distribution of calmodulin with midbody and its involvement in cytokinesis
      regulation].
AB  - Calmodulin (CaM) is a major cytoplasmic Ca2+ receptor and performs a multiplicity
      of functions in the cell. By using GFP-CaM fusion protein, we have studied the
      detailed dynamic redistribution of CaM during cytokinesis in HeLa cells. CaM
      associates with midbody in late cytokinesis phase. When the cells were treated
      with Ca2+/CaM inhibitor W7, the dissolving of the midbody was delayed. Moreover,
      we have found that gamma-tubulin colocalized with CaM at the midbody during
      cytokinesis. W7 treatment could affect the dissociation of gamma-tubulin from
      midbody. These results suggest that CaM may involve in the regulation of midbody
      microtubules disassembly and may thus affect the completion of cytokinesis.

PMID- 14724945
TI  - [Development of a K562 multidrug-resistant cell line and study on proteins with
      altered expression].
AB  - In an attempt to study the whole protein expression alterations of tumer cells
      after becoming multidrug-resistant, which may provide useful information on new
      drug target identification, an adriamycin-resistant variant of the human leukemia
      cell line K562 (K562/ADR) was developed in vitro by continuous exposure to
      adrimycin. MTT assay was used to determine IC50 of K562/ADR cells to adriamycin
      (ADR), cisplatin (DDP), 5-fluorouracil (5-FU) and vincristin (VCR). The total
      proteins of K562 and K562/ADR were separated by two-dimensional gel
      electrophoresis and visualized by silver staining. Proteins with significant
      expression alterations were selected and their peptide mass fingerprints (PMFs)
      were obtained by matrix-assisted laser desorption/ionization time of flying mass
      spectrometry (MALDI-TOF-MS). The PMFs were used to search NCBInr database by
      AutoMS-Fit software. The results showed that K562/ADR cell demonstrated cross
      resistance to other antineoplastic drugs. The IC50 of K562/ADR cells to ADR, DDP,
      5-FU, VDR were much higher than those of K562. The proteins differentially
      expressed in the two cell lines were identified as cell cycle-related proteins,
      zinc finger protein 165, etc. These proteins are involved in cell cycling and
      transcription regulation, whose expression alterations may contribute to the
      multidrug resistant phenotype of K562/ADR cells.

PMID- 14724946
TI  - [Relationship between floral differentiation and endogenous hormones and
      polyamines contents in cucumber cotyledonary nodes cultured in vitro].
AB  - Changes of endogenous hormones and polyamines(PAs) contents during floral
      differentiation (0-6 day) in cucumber cotyledonary nodes cultured in vitro were
      determined by using HPLC. The results showed that all four endogenous hormones
      decreased obviously within 0-2 day and increased slightly within 4-5 day after
      culture. This indicated that low levels of indole-3-acetic acid (IAA),
      gibberelline(GA3) and abscisin acid(ABA) during 0-2 day were favorable to floral
      primordia differentiation, while high level of zeatin(ZT) during 3-5 day was
      favorable to floral organ primordia differentiation. Contents of spermine(Spm),
      spermidine(Spd) and cadavarine(Cad) were decreased within 0-1 day, but increased
      within 1-4 day, and then decreased again within 4-5 day after culture. On the
      contrary, content of putrescine(Put) was increased significantly on the first day
      and then declined during 1-6 day. Changes of PAs contents indicated that high
      levels of PAs and Put were favorable to floral primordia differentiation, the
      increasing of Spm after the second day was favorable to floral organ primordia
      differentiation, and change of Cad content may be one of the characteristic
      symbols between floral and vegetative bud differentiation.

PMID- 14724947
TI  - [Histological observation on programmed cell death in wheat--leaf rust fungus
      intreactioin].
AB  - The ultrastructural features of mesophyll cell surrounding the fungus in
      different interaction between wheat and Puccinia recondita f. sp tritici were
      observed with transmission electron microscopy. In incompatible combination(cv.
      lorvin 10 x race 162), the nuclei gradually became irregular with highly
      condensed chromatin towards the nuclear envelope, while the chloroplast became
      swelling since 12 h to 24 h after inoculation(a.i.). At 48 h a.i., the
      condensation of the chromatin became more prominent and the chloroplast began to
      disintegrate. Finally, when some mitochondria started to degrade at 72 h a.i.,
      the nuclei and the chloroplast became disruption completely. During the process,
      endoplasmic reticulum and vesicles did play a vital role in the further
      degeneration of other organelles and protoplasmic components just similar to the
      lysosome acting in the animal cells. These results suggest that the
      ultrastructural feature of cell death is a form of programmed cell death (PCD).
      In compatible combination (cv. lorvin 10 x race 165), ultrastructural of
      mesophyll cell exhibited different features from incompatible combination. At 24
      h a.i., the plasmic membrane showed sunken and the chloroplast slightly exhibited
      swelling. Since 48 h to 72 h a.i., most of the swelling chloroplasts were
      observed while the other organelles still remained unaltered. At the same time,
      the hypha and haustorium mother cell in the intracellular space also could be
      observed.

PMID- 14724948
TI  - [Development of aloin cells and accumulation of anthraquinone in aloe leaf].
AB  - The development of aloin cells and its relationship with the accumulation of
      anthraquinone in aloe leaf were investigated with the methods of paraffin
      section, semi-thin section, histochemistry and fluorescent microscopy. The
      results showed: cells rounded the procambium bundle differentiated into bundle
      sheath at the initial stage of procambium bundle developing into vascular bundle.
      When the sieve tube members appeared in protophloem, there were a lay of
      procambium bundle cells reserved between the sieve tube members and bundle
      sheath. These cells began to devise, then developed into aloin cells through
      enlargement of volume and vacuolization with the differentiation of metaphloem
      and metaxylem. So the aloin cells were special phloem parenchyma cells because
      they shared the same origin with the other phloem cells. The investigation of
      histochemistry reflected that there were aloin precipitate in the central vacuole
      of aloin cells after the material was soaked in the liquid of 1% lead acetate [Pb
      (CH3COO)2]. In addition, the yellow fluorescence was observed in aloin cells when
      the section of fresh material was investigated under the fluorescent microscope
      with blue light, which suggested the aloin cells of vascular bundles were the
      mainly storage site of anthraquinone.

PMID- 14724949
TI  - [Localization of the estrogen receptor alpha and beta-subtype in the nervous
      system, Hatschek's pit and gonads of amphioxus, Branchiostoma belcheri].
AB  - Immunocytochemical localization were investigated in the nervous system, wheel
      organ, Hatschek's pit and gonads of amphioxus using polyclonal antibodies against
      estrogen receptor-alpha and beta. The results revealed that ER-alpha and beta
      protein distributed in the above regions in larvae and adult at different
      developmental stages of both sexes. A major ER-alpha were expressed within
      nucleus of nerve cells, a few expressed in the cytoplasm and process as well as
      fiber of nerve cells in the forebrain, midbrain, hindbrain and nerve tube, while
      ER-beta were detected in the cytoplasm or on the cellular membrane, a few were
      within nucleus. ER-alpha immunopositive material distributed mainly in the
      nucleus of epithelial cells in the second layer of Hatschek's pit, a few were in
      the cytoplasm of upper layer epithelial cells, while ER-beta distributed in the
      nucleus of upper layer. In gonads, ER-alpha were distributed in the cytoplasm and
      nucleolus of oogonia and oocyte of small growth stage, germinal vesivle(nucleus)
      showed immunonegative reaction. In the large growth stage, strong immunopositive
      reaction were showed in nuclear membrane and nucleolus of oocyte, and within
      nucleus of mature egg cell in the mature stage. ER-beta immunopositive material
      distributed in the cytoplasm of oogonia and early oocytes as well as egg envelope
      of mature egg cell, the germinal vesicle showed immunonegative reaction. In
      testis, both ER subtype were localized in the cytoplasm of spermatogonia, primary
      and second spermatocyte as well as Sertoli cell, and within nucleus of spermatid
      cell, while spermatozoa showed immunonegative reaction. On the other hand, the
      results of double staining revealed that ER-alpha and beta numerously coexisted
      in a same cell, and fewly expressed in different cells in above regions. It is
      found for the first time that both estrogen receptor subtype, which mediated the
      regulate role of estrogen to neuroendocrine tissues in amphioxus, distributed
      extensively in amphiuoxus. The different localization of ER-alpha and beta
      receptor in the target cells suggests that the mediating estrogen signal line and
      the mechanism of gene transcription may be different.

PMID- 14724950
TI  - [The proliferation profile in vitro and anti-tumor effects of dendritic cells co
      culturing with CIK cells].
AB  - To observe the changes of phenotype, proliferation activity and cytotoxicity of
      CIK(cytokine induced killer) cells after co-culturing with dendritic cells(DCs),
      DCs and CIK cells were generated, respectively, by cytokines induction of
      culturing PBMC of healthy blood donor. The typical DCs and DCs pulsed by A549
      lung cancer cells lysate antigen were co-cultured with CIK cells, respectively.
      Cell surface markers were analyzed by FACS method. IFN-gamma and IL-12 secreted
      by CIK cells and co-cultured cells were detected by ELISA. The cytotoxicities of
      effective cells on A549 cells and BEL-7404 cells in vitro were measured by MTT
      assays. The results showed that co-culture of DCs with CIK cells produced a new
      cell population, whose proliferation activity and cytotoxicity were much higher
      than CIK cells. The co-culture stimulated the maturation of DCs. The co-culture
      of CIK cells and A549 cells lysate antigen pulsed DC resulted in an enhanced
      killing activity to A549 cells than CIK cells and un-pulsed DC-CIK cells(p <
      0.05). In conclusion, CIK cells co-cultured with DCs are more powerful than CIK
      cells alone in anti-tumor reaction.

PMID- 14724952
TI  - [Expression of estrogen receptor beta in the hypothalamic paraventricular nucleus
      of postnatal female mice].
AB  - Previous studies have revealed that estrogen receptor beta (ER-beta) in the mouse
      hypothalamic paraventricular nucleus (PVN) may play different roles from that in
      the PVN of rat and other animal species. In the present study, the expression of
      ER-beta in the developing PVN of postnatal female mice was studied using nickel
      ammonium sulfate intensified immunocytochemical techniques, and the results
      showed that ER-beta immunopositive materials were predominantly localized in the
      magnocellular division of the PVN, only sparse positive cells were found in the
      parvocellular division and dorsal cap of the PVN. Most of the positive cells were
      strongly labeled, but some lightly labeled cells were also detected. No apparent
      positive signals were observed in the cytoplasm or the processes of the neurons.
      The highest levels of expression were found at early postnatal days (postnatal
      day 1 to 9), and then it decreased to lower levels from day 15 and thereafter.
      The above results together with other findings suggest that at early postnatal
      development, ER-beta may play important role in the regulation of the structure
      and function of PVN, such as neuroendocrine, morphological maturation, food
      intake and body weight increase of postnatal animals.

PMID- 14724951
TI  - [Molecular chaperone GRP75 reprove cells from injury caused by glucose
      deprivation].
AB  - Glucose-regulated proteins 75(grp75) is a member of hsp70 family. The expression
      of grp75 is upregulated during glucose starvation (such as ischemia). To evaluate
      grp75 function, CHL cells were cultured with glucose-free media for 20 h (A) and
      glucose-free media for 12 h + glucose-containing media for 8 h (ischemia
      reperfusion) (B). A constructed rat grp75 cDNA expression vector (pcDNA/grp75)
      was transfected into CHL cells and a cell strain that stably overexpressed grp75
      was obtained. The transfected cells and untransfected cells(control group) were
      cultured with A or B. By MTT, LDH leakage measurement and flow cytometry
      analysis, growth rate of untransfected cells in B is significantly lower than
      that in glucose-containing media for 20 h (C) (p < 0.05) and A (p < 0.05). Growth
      rate of transfected cells is apparently higher than that of control group in B (p
      < 0.01). LDH liberation percentage of untransfected cells in B is obviously
      higher than that in C(p < 0.01) and it is not different from A(p > 0.05). LDH
      liberation percentage of transfected cells is apparently lower than that of
      control group in B(p < 0.01). Apoptosis of transfected cells is obviously lower
      by flow cytometry analysis. These results provide evidence for the cytoprotective
      function of grp75 during glucose starving and ischemia reperfusion.

PMID- 14724953
TI  - Physical mapping of the 45S and 5S rDNA in Coix lacryma-jobi L.

PMID- 14724954
TI  - [Study of blue light induced DNA damage of retinal pigment epithelium(RPE) cells
      and the protection of vitamin C].
AB  - To evaluate protection of vitamin C on blue light-induced DNA damage of human
      retinal pigment epithelium (RPE) cells. The cultured RPE cells were divided into
      3 groups: Control group (no blue light exposure), blue light exposure group (blue
      light exposure for 20 minutes) and blue light exposure + vitamin C group (blue
      light exposure + 100 mumol/L vitamin C). Travigen's comet assay kit and Euclid
      comet assay software were used to assay the DNA damage levels. The DNA percentage
      in the tail of electrophoretogram in the three groups were 18.44%, 54.42% and
      32.43% respectively (p < 0.01). Tail moments were 8.2, 48.3, and 18.4
      respectively (p < 0.01). Blue light could induce DNA damage to RPE cells but
      vitamin C could protect the RPE cells from the blue light-induced DNA damage.

PMID- 14724955
TI  - [A simple and universal method for molecular sexing of birds].
AB  - It is difficult to sex monomorphic or juvenile birds only according to their
      appearance or by simple surgical techniques. However, the sex of individual bird
      has to be identified during breeding. Recently, a sex-linked gene, CHD1, has been
      discovered in non-ratite birds. Using highly conserved primers flanking the
      intron of CHD1 and PCR amplification, females are characterized by diaplaying two
      fragments(CHD1W and CHD1Z), while males only show one fragment(CHD1Z) clearly
      different in size from the female-specific CHD1W fragment. PCR-based molecular
      sexing method has been widely used due to its many merits over other techniques.
      In this work, we successfully sexed 86 bird from 9 species using this technique.
      All of these birds are listed here as the national first-grade wildlife of China
      for protection. Our results benefit greatly on breeding rare monomorphic birds
      and preventing them from distinction.

PMID- 14724956
TI  - Mental disorder, violence, and gender.
AB  - Recent studies have reported comparable rates of violence among men and women
      with mental disorder, raising important issues for clinical risk assessment. This
      study examines the relationship between gender and violence using data from the
      MacArthur Violence Risk Assessment Study. Patients in acute psychiatric wards
      were interviewed 5 times over the year following their discharge to the
      community. Results showed some differences between men and women in the violence
      committed immediately following discharge, with rates for men being higher. But
      the prevalence of violence over the 1 year was similar for female and male
      discharged patients. However, there were substantial gender differences in the
      situational context of the violence committed. Men were more likely to have been
      drinking or using street drugs, and less likely to have been adhering to
      prescribed psychotropic medication, prior to committing violence. The violence
      committed by men was more likely to result in serious injury than the violence
      committed by women, and men were more likely than women to be arrested after
      committing a violent act. Women were more likely to target family members and to
      be violent in the home.

PMID- 14724957
TI  - The impact of confidence on the accuracy of structured professional and actuarial
      violence risk judgments in a sample of forensic psychiatric patients.
AB  - Some previous research indicates that confidence affects the accuracy of
      probabilistic clinical ratings of risk for violence among civil psychiatric
      inpatients. The current study investigated the impact of confidence on actuarial
      and structured professional risk assessments, in a forensic psychiatric
      population, using community violence as the outcome criteria. Raters completed
      the HCR-20 violence risk assessment scheme for a sample of 100 forensic
      psychiatric patients. Results showed that accuracy of both actuarial judgments
      (HCR-20 total scores) and structured professional judgments (of low, moderate,
      and high risk) were substantially more accurate when raters were more confident
      about their judgments. Findings suggest that confidence of ratings should be
      studied as a potentially important mediator of structured professional and
      actuarial risk judgments.

PMID- 14724958
TI  - Is there touch in the game of Twister? The effects of innocuous touch and
      suggestive questions on children's eyewitness memory.
AB  - Preschool children (ages 48-70 months, N = 48) experienced 2 to-be-remembered
      events (i.e., the games Twister and Shapes) that included either innocuous bodily
      touch or no touch. Participants were interviewed 7 days later and asked direct
      ("Did Amy kiss you?") or suggestive "tag" questions ("Amy kissed you, didn't
      she?") equated for content. Results indicated that children who were innocuously
      touched were no more likely to falsely assent to "abuse-related" touch questions
      (e.g., "Amy touched your bottom, didn't she?") than were children who were not
      touched. However, children who were asked tag questions responded at chance
      levels, thereby making high errors of commission in response to abuse-touch
      questions relative to their no-tag counterparts who responded to "abuse
      questions" accurately 93% of the time. Children who were asked tag questions
      assented at a higher rate to general forensic questions ("Amy took your picture,
      didn't she?") than did children asked direct questions, and children assented at
      higher rates to "abuse-touch" questions than to general forensic questions.
      Results are discussed in terms of prior research on interviewing techniques and
      adult influence on children's testimony.

PMID- 14724959
TI  - Explaining capital punishment support in an abolitionist country: the case of The
      Netherlands.
AB  - A substantial minority (35%) of the Dutch population is in favor of capital
      punishment. In this paper, it is argued that in a staunchly abolitionist country
      such as The Netherlands, the existence and perseverance of such support can be
      better understood and explained by conceiving of capital punishment support in
      attitudinal terms as part of a law and order syndrome. Death penalty attitudes
      are analyzed by means of hierarchic logistic regression analysis. It is shown
      that support can be modeled quite well, partly in terms of general attitudes to
      criminal justice, partly in terms of political and sociodemographic parameters.
      Within the criminal justice attitudes complex, more support is found among those
      endorsing harsh treatment of offenders, those willing to grant far-reaching
      powers to justice authorities, those believing that the government is not
      delivering on the topic of crime fighting, and those who are concerned about the
      level of crime. Within the political context, more support is enlisted among
      people who abstain from voting and those who vote at either extreme of the
      political spectrum as opposed to central parties' supporters. In sociodemographic
      segments it is the younger and poorly educated who are the strongest supporters
      of capital punishment. It is suggested that endorsing capital punishment can be
      better understood as an expressive act, displaying dissatisfaction with judicial
      and political elites in the country.

PMID- 14724960
TI  - Murder, extramarital affairs, and the issue of probative value.
AB  - A paper previously published in Law and Human Behavior by D. Davis and W. C.
      Follette (2002) argued that certain "profiling" characteristics commonly admitted
      into court have little or no probative value. They argued that this is especially
      likely to be true when the characteristic used as evidence (e.g., having an
      extramarital affair) is rather common in the population whereas the act in
      question (e.g., a man murdering his wife) is rare. Their analysis has prompted a
      strong response by Friedman and Park and by Kaye and Koehler with a rejoinder by
      Davis and Follette (all three follow this paper in this issue of Law and Human
      Behavior). This paper describes some of the nature of this controversy.

PMID- 14724961
TI  - Sometimes what everybody thinks they know is true.
AB  - This essay responds to D. Davis and W. C. Follette (2002), who question the value
      of motive evidence in murder cases. They argue that the evidence that a husband
      had extramarital affairs, that he heavily insured his wife's life, or that he
      battered his wife is ordinarily of infinitesimal probative value. We disagree. To
      be sure, it would be foolish to predict solely on the basis of such evidence that
      a husband will murder his wife. However, when this kind of evidence is combined
      with other evidence in a realistic murder case, the evidence can be quite
      probative. We analyze cases in which it is virtually certain that the victim was
      murdered but unclear who murdered her, and in which it is uncertain whether the
      husband murdered the wife or she died by accident. We show that in each case
      motive evidence, such as a history of battering or of infidelity, can
      substantially increase the odds of the husband's guilt. We also consider the
      actual case on which Davis and Follette base their paper. We argue that testimony
      of Davis on the basis of the analysis presented in their paper was properly
      excluded, for it would have been misleading and unhelpful.

PMID- 14724962
TI  - The misquantification of probative value.
AB  - D. Davis and W. C. Follette (2002) purport to show that when "the base rate" for
      a crime is low, the probative value of "characteristics known to be strongly
      associated with the crime ... will be virtually nil." Their analysis rests on the
      choice of an arbitrary and inopposite measure of the probative value of evidence.
      When a more suitable metric is used (e.g., a likelihood ratio), it becomes clear
      that evidence they would dismiss as devoid of probative value is relevant and
      diagnostic.

PMID- 14724963
TI  - Toward an empirical approach to evidentiary ruling.
AB  - This paper responds to criticisms/misconstruals of our measure of the maximum
      probative value of evidence (D. Davis & W. C. Follette, 2002), and our
      conclusions regarding the potentially prejudicial role of "intuitive profiling"
      evidence, including motive. We argue that R. D. Friedman and R. C. Park's (2003)
      criticisms and example cases are largely based on inappropriate violation of the
      presumption of innocence. Further, we address the merits of our absolute
      difference measure of probative value versus those of the Bayesian likelihood
      ratio championed by D. H. Kaye and J. J. Koehler (2003). We recommend methods for
      presentation of measures of evidence utility that convey complexities of
      interdependence between new and existing evidence. Finally, we propose a
      "probable cause" standard for admission of potentially prejudicial evidence,
      dictating that admissibility of such evidence should be contingent upon other
      substantial evidence of guilt.

PMID- 14724964
TI  - [Achievements in the diagnosis and treatment of immune myocarditis].

PMID- 14724965
TI  - [Endovascular surgery in cardiac and vascular diseases in the 21st century].

PMID- 14724966
TI  - [The development and clinical testing of antiarrhythmia drugs of a new chemical
      class].

PMID- 14724967
TI  - [New biotechnologies in the immune diagnosis of impaired vessels in patients with
      rheumatic diseases].

PMID- 14724968
TI  - [Psychological and psychiatric approaches to the prevention and treatment of
      cardiovascular diseases].

PMID- 14724969
TI  - [The autoimmune theory of the pathogenesis of atherosclerosis and related new
      treatment ways].

PMID- 14724971
TI  - [The occupational conditions as a risk factor in the development of
      cardiovascular diseases].

PMID- 14724970
TI  - [Pharmacological regulation of emotional stress reactions].

PMID- 14724972
TI  - [Human cardiovascular system under the conditions of a space flight].

PMID- 14724973
TI  - [Possibilities of the low-intensity infrared laser therapy in atherosclerotic
      lesions of the cardiovascular system].

PMID- 14724974
TI  - [Acute respiratory diseases and the heart].

PMID- 14724975
TI  - [Cardiovascular lesions in infectious diseases].

PMID- 14724976
TI  - [Development of original Russian antiarrhythmic drugs of the 3rd class].

PMID- 14724977
TI  - [X-ray diagnosis of cardiovascular pathologies: new outlooks].

PMID- 14724978
TI  - [Neuro-resuscitation in stroke: state-of-art].

PMID- 14724979
TI  - [Cerebral mechanisms in the genesis of arterial hypertension in emotional
      stress].

PMID- 14724980
TI  - [Current possibilities of the reconstructive vascular surgery and the outlooks
      for using genetic engineering in critical ischemia of the lower extremities].

PMID- 14724981
TI  - [Cardiovascular diseases in the newborn: cardiological and surgical aspects].

PMID- 14724982
TI  - [The Resolution of the LXXV Session of the General Assembly of the Russian
      Academy of Medical Sciences].

PMID- 14724983
TI  - [The molecular and virological specificities of the epidemic of HIV infections in
      Russia and other CIS countries].

PMID- 14724984
TI  - [Ethnic genomics and hereditary fundamentals of prevalent diseases].

PMID- 14724985
TI  - [Exogenous donors of nitric oxide and inhibitors of NO-synthase (chemical
      aspects)].

PMID- 14724986
TI  - [Poverty, air pollution, rage attacks, loneliness. Surprising heart risks].

PMID- 14724987
TI  - [Anticoagulation in atrial fibrillation. Instead of costly therapy control soon a
      tablet for all?].

PMID- 14724988
TI  - [Optimistic 3-year data. Berlin surgeon develops heart valves from autologous
      patient tissue].

PMID- 14724989
TI  - [Heart failure. Can vasopressin antagonists improve the prognosis?].

PMID- 14724990
TI  - [German stem cell study in myocardial infarct patients. Bone marrow improves the
      power of myocardial contraction].

PMID- 14724991
TI  - [When drugs are not enough: electrical impulses in Parkinson disease, epilepsy
      and pain].

PMID- 14724992
TI  - [Disturbed about a "happy title picture". Freely laughing seniors--or very
      successful?].

PMID- 14724993
TI  - [Hydrogen peroxide: expensive quackery?].

PMID- 14724994
TI  - [Early detection of stomach cancer. What we should learn from the Japanese].

PMID- 14724995
TI  - [Patient after stomach resection. What and how he should eat].
AB  - Complete or partial removal of the stomach results in considerable anatomical and
      physiological changes, which, in turn lead to more or less pronounced dietary
      problems. For this reason, patients should receive comprehensive postoperative
      counseling. In the majority of cases, the major problems can be avoided or
      symptoms ameliorated. The selection of suitable foods must be discussed, as also
      the particular importance of drinking. Preprandial exercise to stimulate the
      appetite is just as important as postprandial resting to avoid diarrhea and the
      dumping syndrome. A central aspect is the distribution of the food ingested over
      six to ten small portions. Some nutrients may need to be substituted--for
      example, vitamin B12, the fat-soluble vitamins, calcium and iron. With increasing
      time after the operation, alimentation problems usually abate, but in the
      individual case may persist for years.

PMID- 14724996
TI  - [From endoscopic mucosa ressection to gastrectomy. How radical must surgery be
      for stomach cancer?].
AB  - The aim of surgical treatment is complete resection (Ro-resection) of the tumor
      in all dimensions of its growth, i.e. resection of the tumor infiltrated stomach
      including the locoregional lymph nodes. This can be achieved by stage- or
      histology adapted surgery resulting in subtotal distal and total gastrectomy as
      complementary procedures. Local excision of gastric carcinoma in curative intent
      is indicated only in mucosal carcinoma of the intestinal type. The extent of
      lymph node dissection is still under discussion; the results depend on the
      experiences of the surgeon. Several studies have shown a prognostic improvement
      after systematic (D2) lymphadenectomy in stage II/IIIA-disease or in patients
      with a low incidence of lymph node metastases. Pancreas preserving splenectomy is
      suggested in tumors of the proximal stomach or after direct infiltration of these
      organs. The Roux-en-Y procedure represents the most commonly used method of
      reconstruction after subtotal distal or total gastrectomy. The importance of the
      duodenal passage as well as of the pouch construction must be investigated in
      prospective studies in the future. This is true for the value of perioperative
      multimodal treatment options.

PMID- 14724997
TI  - [Adjuvant therapy concepts in advanced stomach carcinoma. Future treatment not
      without irradiation?].
AB  - Perforation of the wall of the stomach, or positive lymph nodes appreciably
      worsens the prognosis of resected gastric carcinoma. In such a situation, neither
      adjuvant chemotherapy [12] nor optimal lymph node resection achieves a
      significant improvement in overall survival [5-8]. In contrast, a significant
      benefit of adjuvant radiochemotherapy after curative resection of advanced
      gastric carcinoma has been demonstrated. Thus, standardized postoperative
      radiochemotherapy should be applied after standardized surgery with a D1
      resection. Optimal supportive treatment, that is, at least 1500 kcal/day,
      appropriate treatment of reflux or dumping symptoms, and supplementation for
      iron, vitamin B12 and calcium deficiency, is mandatory, if therapeutic success is
      not to be compromised [13,14].

PMID- 14724998
TI  - [Patient with stomach cancer with metastases. What is the value of
      chemotherapy?].
AB  - In comparison with supportive measures alone, chemotherapy in advanced gastric
      carcinoma is associated with a significant increase in survival and improvement
      in quality of life. The following substances are considered to be effective and
      suitable for combination therapy: 5-FU +/- folic acid, cisplatin, irinotecan,
      etoposide, taxol, and taxotere. In contrast, the effect of doxorubicin and
      epidoxorubicin is only moderate. Although "second generation" combinations, such
      as FAMTX, ELF or cisplatin/5-FU, induced higher remission rates as the "first
      generation" combinations, they failed to improve survival times to any
      appreciable extent. Currently accepted standard treatment of metastatic gastric
      carcinoma is infusional 5-FU + cisplatin or ECF. The third generation
      combinations containing taxane, irinotecan, oxaliplatin appear to be at least
      equally effective.

PMID- 14724999
TI  - [Too many osteoporosis patients are undertreated with analgesics. Chronic pain
      promotes bone loss].
AB  - The leading subjective symptom of osteoporosis is severe or intolerable back
      pain. Resulting partial or complete immobilization increases the risk of muscular
      atrophy and bone loss, and thus the risk of fractures. Pain management in
      osteoporotic patients is either not applied at all, or only inadequately. When
      pain and immobility are pronounced, primary treatment with opioids and
      individually adapted co-analgesics is called for. Initial experience with opioid
      therapy in osteoporosis reveals rapid amelioration and improved mobility. Concern
      about addiction, development of tolerance and problems on discontinuation are
      unjustified.

PMID- 14725000
TI  - [Synopsis of differential diagnoses. The painful eye].

PMID- 14725001
TI  - [Increased healing rate, fewer dressing changes. Sealing wounds with vacuum].

PMID- 14725002
TI  - [Expert round table discussion in Munich confirms it. Hexavalent vaccination
      offers comprehensive prevention].

PMID- 14725003
TI  - [Effectiveness of vaccinations. Vaccination goals are achieved].

PMID- 14725004
TI  - [Hexavalent vaccines evaluated in general practice. High compliance, good
      tolerance].

PMID- 14725005
TI  - [HDL cholesterol as protective factor. Deficiency threatens the diabetic heart].

PMID- 14725006
TI  - [Sinusitis: initially not an indication for antibiotics. 5 plants relieve the
      paranasal sinuses].

PMID- 14725007
TI  - [It impairs quality of life and work time. Migraine therapy should not be left to
      the patients!].

PMID- 14725008
TI  - [Added organ protection at little cost. Double savings with ACE inhibitors].

PMID- 14725010
TI  - The meaning of life.

PMID- 14725011
TI  - Power politics and social responsibility.

PMID- 14725009
TI  - [Pegylated alfa-2a in hepatitis B. Fewer injections with better results?].

PMID- 14725012
TI  - Patients and chronic pain.

PMID- 14725013
TI  - The history of rehabilitation in Maryland.

PMID- 14725014
TI  - Orthopaedic rehabilitation. Getting moving again.

PMID- 14725015
TI  - Acute rehabilitation.

PMID- 14725016
TI  - Spinal cord injury medicine.
AB  - Spinal cord injury/spinal cord rehabilitation provides comprehensive
      rehabilitation care to reach the patient's functional goals in an acute
      inpatient, subacute, home, and/or outpatient rehabilitation setting. Spinal cord
      injury/spinal cord medical specialists are trained specifically on the evaluation
      and management of the unique medical and surgical conditions among those
      following SCI. They are trained in the care and rehabilitation of persons with SC
      dysfunction resulting from traumatic or non-traumatic spinal cord injuries and
      work in coordination both in clinical care and research with a variety of other
      medical and surgical specialists, for the care and optimum functional recovery
      for patients with SCI. These specialists work within a comprehensive rehab team
      including nursing staff and physician extenders, therapists, psychologists,
      respiratory staff, nutritionists, case managers, social workers, and vocational
      rehabilitation counselors for patients with SCI. There are a number of resources,
      clinics, and inpatient rehabilitation units in the Maryland area that provide
      this subspecialty care.

PMID- 14725017
TI  - Rehabilitation psychology. Overview and key concepts.
AB  - Rehabilitation is based on the biopsychosocial model, which includes attention to
      medical, psychological and social aspects of illness and recovery. As part of an
      interdisciplinary rehabilitation team, mental health professionals evaluate and
      treat common emotional, cognitive, and behavioral problems. They can promote a
      patient-centered and individualized approach to care. Current psychological
      interventions in rehabilitation include cognitive, behavioral, family-based, peer
      support and positive psychology models. Cognitive remediation techniques can be
      used to improve the function of people with brain dysfunction. In partnership
      with physicians and other rehabilitation professionals, rehabilitation
      psychologists play an integral role in improving functional, psychosocial and
      health outcomes in chronic illness and disability.

PMID- 14725018
TI  - Maryland's future demand for rehabilitation.

PMID- 14725019
TI  - Rehabilitation: essential to the continuum of care.

PMID- 14725020
TI  - Ethics & medical enterprise: the consultant conundrum.

PMID- 14725022
TI  - Rehabilitation.

PMID- 14725021
TI  - Tort reform also crucial to your staff.

PMID- 14725023
TI  - [Undermanagement of patients with rheumatism. Know-how too often not utilized].

PMID- 14725024
TI  - [Interview with Prof. Dr. Herbert Kellner. Basic rheumatologic knowledge for the
      family physician (interview by Martin Bischoff)].

PMID- 14725025
TI  - [Oral vaccines--a future prospect! Hepatitis vaccination in the vegetable
      market?].

PMID- 14725026
TI  - [Refractory borreliosis--failed antibiotic treatment--what now? Reconsider the
      diagnosis!].

PMID- 14725027
TI  - [Beta blocker in heart failure. Dosage too low].

PMID- 14725028
TI  - [Aggressive management of asthma. "Wait it out" is the worst advice].

PMID- 14725029
TI  - [High rate of undetected compulsive disorders. First concealed, then not detected
      (interview by Erik Heintz)].

PMID- 14725030
TI  - [Hypertensive female patients often undertreated or treated too late. Therapy of
      hypertension needs women's initiative].
AB  - Both the cardiovascular risk profile and the incidence of arterial hypertension
      are known to show gender-specific differences. In postmenopausal women, the
      cardiovascular risk is clearly elevated. At particular risk are women with
      diabetes mellitus, overweight and hypertriglyceridemia. In numerous clinical
      studies on the treatment of arterial hypertension, however, the percentage of
      women involved is small, and not representative. Furthermore, studies on the
      confirmation of the diagnosis and treatment show that treatment of hypertension
      in female patients has often been less effective and less rigorously applied than
      in men. At the same time, it is known that the success of rigorous risk reduction
      is independent of gender.

PMID- 14725031
TI  - [Circadian rhythm of silent myocardial ischemia. Why morning is so risky for
      hypertensive patients].
AB  - The circadian pattern of numerous cardiovascular events (myocardial infarction,
      sudden cardiac death, stroke) reveals a peak in the early hours of the morning. A
      circadian rhythm peaking in the morning is also found for so-called silent
      myocardial ischaemia, which occurs in more than 20% of patients with arterial
      hypertension, and can be regularly detected in combined 24-h-ABPM/EKG
      examinations. Comparative studies have shown that hypertensives with SMI suffer
      more cardiac events than those with no SMI. It has further been demonstrated that
      an elevated blood pressure amplitude, with is considered an independent risk
      factor for cardiac events, is associated with an increased incidence of SMI in
      patients with micro- or macro-angiopathy. Accordingly, consideration should be
      given to SMI when deciding on treatment, also in hypertensives with no angina
      pectoris symptoms.

PMID- 14725032
TI  - [Atrial fibrillation as end point of hypertension. Can antihypertensive therapy
      prevent it?].
AB  - The most effective and safest option for the prevention of atrial fibrillation
      and its sequelae--cardiovascular morbidity and mortality, stroke)--is primary
      prophylaxis. Here, the management of arterial hypertension--the most common cause
      underlying atrial fibrillation--is of considerable importance. In addition to
      blood pressure reduction, substances with an action of the autonomic nervous
      system and the renin-angiotensin-aldosterone system (ACE-inhibitors, AT1
      antagonists, beta blockers) have a positive effect on the remodeling, so-called,
      of the atrial myocytes, and thus on the occurrence of atrial fibrillation with
      its associated stroke risk. For patients with elevated blood pressure, therefore,
      the therapeutic strategy should, in the individual case, give consideration to
      the possibility of exerting a positive effect on atrial fibrillation.

PMID- 14725033
TI  - [Aldosterone receptor antagonists in heart failure. Rightly brought back from
      retirement].
AB  - There is growing evidence that aldosterone plays an important role in the
      development of endorgan-damage e.g. vascular and cardiac fibrosis, remodeling and
      endothelial dysfunction. Aldosterone-antagonism has become a novel therapeutic
      principle beyond its sodium retention properties in the treatment of
      cardiovascular diseases. In patients with severe left ventricular dysfunction
      spironolactone could reduce death and hospitalisation. A new selective
      aldosterone antagonist, eplerenone, was effective in patients with left
      ventricular dysfunction after myocardial infarction added to optimal medical
      therapy.

PMID- 14725034
TI  - [Physical activity in hyperglycemia and type 2 diabetes. Effective but still
      underutilized].

PMID- 14725035
TI  - [Treatment of hypertension in a clinical trial. Depot alpha 1 blocker simplifies
      dosing].

PMID- 14725036
TI  - [Treatment of arthrosis with collagen hydrolysate. From empiricism to evidence-
      an effective therapeutic principle comes through].

PMID- 14725037
TI  - [Clinical studies with collagen hydrolysate demonstrate: joint pain improved].

PMID- 14725038
TI  - [SSRI enantiomers already effective after 8 days. The proper twist against
      depression].

PMID- 14725039
TI  - [Because hepatic encephalopathy is a frequent contributing factor. Patients with
      liver cirrhosis are poorer drivers].

PMID- 14725040
TI  - [Colitis therapy becomes more acceptable for patients. Rectal foam instead of
      enema].

PMID- 14725041
TI  - [Two drugs have a better outcome. Finasteride plus alpha blocker improves urine
      flow].

PMID- 14725042
TI  - [Therapy of hypertension. Cost conscious prevention of complications].

PMID- 14725044
TI  - [Migraine].

PMID- 14725043
TI  - [Health care too costly? Saving more than 10 million euros in 2 months!].

PMID- 14725045
TI  - [Spontaneous femoral neck fracture in idiopathic polyneuropathy. A preventable
      complication].

PMID- 14725046
TI  - [Growth on the right side of the nose].

PMID- 14725047
TI  - [49. Phobic disorder, panic or generalized anxiety? Basic principles in diagnosis
      and therapy].

PMID- 14725048
TI  - [Current diagnostics and therapy of focal liver lesions].
AB  - Increasing number of tumorous diseases, the extension of Hepatitis B and C
      infection, and growing frequency of cirrhotic patients have emphasized the
      importance of treatment of primary and secondary liver tumors. On the other hand
      the development in imaging procedures have been resulted in diagnosis of
      different focal liver lesion with unknown origin, and had to decide whether the
      patient should be treated or only observation is indicated. First the author
      gives a review about the most frequent focal liver lesions and their therapeutic
      consequence. He discusses in detail the indication, risk factors, technics,
      contraindications and complications of surgical interventions. The possibilities
      and results of ablative and minimal invasive procedures are analysed, and the
      author underlines the necessity of combined therapy. The results of different
      therapeutic modalities are presented according to literary data, and the author
      summarizes the therapeutic tactics accepted today.

PMID- 14725049
TI  - [Role of minimally invasive interventions in the treatment of complications
      caused by recidive Klatskin tumors].
AB  - BACKGROUND: The hilar cholangiocarcinoma grows slowly and gives metastases very
      rarely. The first prominent sign of this cancer is the jaundice. In spite of the
      small size of the tumour, oncologically radical resection is only feasible--owing
      to the anatomical position--in approximately 35-50% of the cases. This makes
      recidivity frequent. The recidive cancer involves the hilus of the liver,
      compresses the surrounding organs and develops different complications. METHODS:
      37 patients underwent surgical resection in the 1st Surgical Department of
      Semmelweis University in the last ten years. Complete tumour-free surgical
      margins were found in only 48.6% of the cases. The mean follow-up was 23.2 (8-47)
      months. RESULTS: 9 patients were treated for complication caused by local
      recurrence. These were mechanical jaundice (9 cases), bleeding oesophageal
      varices (2 cases), gastric outlet obstruction (2 cases), liver abscess (3 cases)
      and pain caused by the infiltration of the coeliac ganglion (3 cases). Most part
      of the complication could be solved by minimal invasive therapy (percutane
      transhepatic endoprosthesis or drainage, endoscopic sclerotherapy, ultrasound
      guided drainage, percutane blockade of the celiac ganglion). CONCLUSIONS: The
      fact that resected patients may survive several years as long as patients treated
      with endoprosthesis and irradiation only survive half a year, has brought a
      change in the way Klatskin cancer surgery is considered: resection of the tumour
      should be striven for--even by way of R1 resection. Therefore the risk of
      recurrence will increase. This is the first article in the literature, which has
      ever dealt with the complication caused by recidive cancer after resection of
      Klatskin tumour.

PMID- 14725050
TI  - [Possibilities of monitoring oxidative damage and its clinical aspects].
AB  - In their earlier work the authors reviewed some methods, which appeared to be
      suitable for monitoring the redox-status of the human organism and, therefore,
      may be applied under routine clinical laboratory circumstances. This possibility
      can lead to a new perspective to set up epidemiological studies in different
      populations in order to investigate connecting points between the manner of life,
      alimentary customs (especially consumption of antioxidants), and the risk of
      chronic or acute illnesses. In this review the authors surveyed different methods
      for the measurements of end products (lipids, proteins, nucleic acids) produced
      by cells and tissues through oxidative injury, caused by the free radicals. These
      methods have already served the work of scientists for many years, helping them
      to obtain experience about the pathomechanisms of different diseases. With the
      help of these measurements it could be possible to monitor the results of medical
      therapy or surgical treatments, or in the field of chronic illnesses e.g.
      diabetes, to predict the possible development of late complications.

PMID- 14725051
TI  - [Value of testing the abdominal leak point pressure in the differential diagnosis
      of urinary stress incontinence].
AB  - INTRODUCTION: The two main reasons of stress incontinence, according to the
      present consensus, are urethral hypermotility due to descended bladder floor and
      intrinsic sphincter deficiency. Distinction between them used to be achieved by
      determining urethral pressure profile only. In recent years a less invasive
      method, measuring the Valsalva Leak Point Pressure, has been developed for a
      differentiation. AIMS: To determine Valsalva Leak Point Pressure using a simple
      technique for differential diagnosis of stress incontinence without a complete
      urodynamic test. METHOD: A minimally invasive technique is presented. Authors
      have performed parallel measurements of leak point pressure and urethral pressure
      profile during urodynamic examination in 43 stress incontinent patients.
      Difference in the results have also been evaluated. RESULTS: A specificity of 98%
      and a sensitivity of 51% with the method was found in intrinsic sphincter
      deficiency. In cases without vaginal descent the sensitivity was 100%, while in
      patients with urethral hypermobility the sensitivity and the specificity were 91%
      and 58% respectively. CONSEQUENCES: In stress incontinent patients without
      urethral hypermotility an abdominal leak point pressure of less than 40 H2O cm
      perfectly reflects weakness of the urethral sphincter. Based on these data we
      suggest that the invasive urethral pressure profile test can be avoided in appr.
      20% of stress incontinence cases by weakness of the sphincter.

PMID- 14725052
TI  - [Development of Basedow disease after radioiodine therapy for nodular goiter].
AB  - It has been observed in the past few years, that radioiodine therapy triggers
      autoimmune thyrotoxicosis. The possible mechanism of this phenomenon is that
      protein fragments enter the circulation after thyroid cell damage induced by
      radiation. TSH-receptor autoantibodies are produced in genetically susceptible
      patients after radiotherapy. In treating nodular goiter--a non-immune thyroid
      disease--with 131I, an immunogenic disorder--Basedow-Graves' disease--may
      develop. The authors present this phenomenon in a case of a 67 year-old woman
      with a history of operation for euthyroid nodular goiter in 1977. In November
      2001, she was admitted to the hospital with local signs and symptoms of relapse
      of euthyroid nodular goiter (TSH-receptor antibodies were not detected). She was
      treated with oral doses of 320 MBq of radioiodine to reduce the thyroid volume.
      Four months after radioiodine therapy the patient had developed signs of
      thyrotoxicosis. At that time TSH-receptor antibodies were found to be positive.
      Thyreostatic therapy was administered and still being in use till today. The
      authors draw the attention to the fact that, when a hyperthyrosis develops after
      radioiodine therapy of a non-immune thyroid disease, the possibility of Graves
      Basedow disease should be raised, especially in a patient with a positive family
      history.

PMID- 14725053
TI  - [Treatment of chronic autoimmune thrombocytopenic purpura (ITP) in adults].

PMID- 14725054
TI  - [Treatment of ANCA-associated primary small-vessel vasculitis].

PMID- 14725055
TI  - Collaborative nursing practice in Alberta.

PMID- 14725058
TI  - Aim high--think big.

PMID- 14725059
TI  - Environmental scan of nursing--encountering the perfect storm.

PMID- 14725062
TI  - Do you screen patients for substance abuse?

PMID- 14725063
TI  - Troubleshooting central lines.

PMID- 14725064
TI  - Taking patient ed to the next level.

PMID- 14725065
TI  - Hormone replacement therapy.

PMID- 14725067
TI  - An endoscopic approach to GERD?

PMID- 14725066
TI  - JCAHO shifts gears.

PMID- 14725068
TI  - Staying safe when understaffed.

PMID- 14725069
TI  - [Expert work during technogenc emergency situations (Report I)].
AB  - The authors discuss the organizational principles of the work of expert
      institution and its subdivisions with reference to technogenic catastrophes
      accompanied with mass human victims. The problems of interaction of the
      representatives from different structures and departments taking part in the work
      at the place of event are considered in terms of forensic medicine. The attention
      is concentrated on the problems of expert institution readiness to work under
      conditions of extreme situations depending on the medicotactical characteristics
      of defeat focus.

PMID- 14725070
TI  - [Features of body functional profile of workers in the state fire prevention
      service].

PMID- 14725072
TI  - [Antibacterial therapy of non-severe extra-hospital pneumonia].

PMID- 14725071
TI  - [Ligation of the internal iliac artery in gunshot wounds of buttocks and pelvis].

PMID- 14725073
TI  - [In vivo flow measurement of blood loss volume in pulmonary tuberculosis patients
      in the early postoperative period].

PMID- 14725074
TI  - [Ozone therapy in the complex treatment of local complications of chronic
      tonsillitis].

PMID- 14725075
TI  - [The lithotriptor "Compact" used in urinary bladder diseases].
AB  - The stroke-wave complex "Compact" is the first home-produced lithotriptor with
      electromagnetic system of stroke-wave generation and ultrasonic diagnosis. During
      its development it was possible to achieve the optimal parameters of focused
      waves, good technical characteristics and economic indices. The clinical use of
      lithotriptor has shown its efficiency in nephrolith and ureterolith remote
      destruction in the absence of complications connected with negative influence of
      stroke waves on kidneys and surrounding organs and tissues.

PMID- 14725076
TI  - [Features of functional myocardial disorders, intracardiac and systemic
      hemodynamics in chronic diffuse liver diseases].

PMID- 14725077
TI  - [Use of low-dose digital fluorography in patients with acute infiltrative
      pulmonary processes].
AB  - Basic purpose of issue was the attempt of a rating of a role and place modern
      digital chest fluorography in complex diagnostics of lower respiratory diseases
      accompanied acute pulmonary infiltrates. We studied 232 adults who hospitalized
      with community-acquired pneumonia (CAP) to Saratov Military Medical School
      Hospital during 1999-2003. In integration of methods of research the role digital
      chest fluorography as way of primary diagnostics and conducting means of the
      analysis of technology of rendering of medical aid is emphasized. At the expense
      of use of the developed algorithm of methods of beam visualization at the control
      of a course of stationary treatment of the patients CAP it was possible to
      decrease length of stay for 2.5 day.

PMID- 14725078
TI  - [Severe acute respiratory syndrome].

PMID- 14725079
TI  - [Efficacy and intolerance of meloxicam in injection and tablet form].

PMID- 14725080
TI  - [Injuries caused by in-flight ejection].
AB  - The localization, causes and severity of 214 "ejection-associated" injuries
      occurred in 160 pilots are discussed. Spine, upper and lower extremities are
      affected most frequently. The severe injures prevail (57.8%). The main causes of
      severe injuries are the impact + Gz accelerations of ejection and the impact + Gz
      accelerations of landing.

PMID- 14725081
TI  - [Modelling of the processes controlling medical property reserves].
AB  - Basing on the study of contents of medical logistics modern system the principles
      for modelling of the processes controlling the medical property reserves in the
      troops and stores were developed. The developed methodology has allowed to define
      the optimal sizes of reserves and to establish the dependence between the troops'
      medical property provision and the efficiency of medical care and treatment
      rendered the casualties and patients.

PMID- 14725082
TI  - [Guarding the health of seamen].

PMID- 14725083
TI  - [From the history of military field surgery].

PMID- 14725084
TI  - [Sources of military phytotherapy].

PMID- 14725085
TI  - [The half-century jubilee of the military sanatorium "Divnomorskoe"].

PMID- 14725086
TI  - [Museums in military hospitals].

PMID- 14725087
TI  - Diversity and adaptation of shelters in transitional settlements for IDPs in
      Afghanistan.
AB  - The diversity of shelters used in transitional settlements for internally
      displaced persons (IDPs) in Herat, Afghanistan is described. The information is
      based on a field survey undertaken in March 2002 and highlights the adaptation
      techniques, which IDPs undertake to improve any provided shelter. Potential areas
      for improvement are indicated; for example, the possibility for using insulated,
      demountable liners to prevent cold-related deaths without sacrificing shelter
      flexibility along with the likely need for better agency coordination of the
      shelter responses they provide. The wider context in which the technical
      recommendations would be implemented must also be considered. Such issues include
      agency resources, political impediments to providing the desired option, and the
      preference of many IDPs that the best shelter would be their home.

PMID- 14725088
TI  - Integration of different data bodies for humanitarian decision support: an
      example from mine action.
AB  - Geographic information systems (GIS) are increasingly used for integrating data
      from different sources and substantive areas, including in humanitarian action.
      The challenges of integration are particularly well illustrated by humanitarian
      mine action. The informational requirements of mine action are expensive, with
      socio-economic impact surveys costing over US$1.5 million per country, and are
      feeding a continuous debate on the merits of considering more factors or 'keeping
      it simple'. National census offices could, in theory, contribute relevant data,
      but in practice surveys have rarely overcome institutional obstacles to external
      data acquisition. A positive exception occurred in Lebanon, where the landmine
      impact survey had access to agricultural census data. The challenges, costs and
      benefits of this data integration exercise are analysed in a detailed case study.
      The benefits are considerable, but so are the costs, particularly the hidden
      ones. The Lebanon experience prompts some wider reflections. In the humanitarian
      community, data integration has been fostered not only by the diffusion of GIS
      technology, but also by institutional changes such as the creation of UN-led
      Humanitarian Information Centres. There is a question whether the analytic
      capacity is in step with aggressive data acquisition. Humanitarian action may yet
      have to build the kind of strong analytic tradition that public health and
      poverty alleviation have accomplished.

PMID- 14725089
TI  - International NGOs and the role of network centrality in humanitarian aid
      operations: a case study of coordination during the 2000 Mozambique floods.
AB  - In February 2000, Mozambique suffered its worst flooding in almost 50 years: 699
      people died and hundreds of thousands were displaced. Over 49 countries and 30
      international non-governmental organisations provided humanitarian assistance.
      Coordination of disaster assistance is critical for effective humanitarian aid
      operations, but limited attention has been directed toward evaluating the system
      wide structure of inter-organisational coordination during humanitarian
      operations. Network analysis methods were used to examine the structure of inter
      organisational relations among 65 non-governmental organisations (NGOs) involved
      in the flood operations in Mozambique. Centrality scores were used to estimate
      NGO-specific potential for aid coordination and tested against NGO beneficiary
      numbers. The average number of relief- and recovery-period beneficiaries was
      significantly greater for NGOs with high relative to low centrality scores (p <
      0.05). This report addresses the significance of these findings in the context of
      the Mozambican 2000 floods and the type of data required to evaluate system-wide
      coordination.

PMID- 14725090
TI  - An exploratory comparison of disasters, riots and terrorist acts.
AB  - One question that emerged following the 11 September attacks was how to
      categorise and classify the event within existing disaster and conflict-event
      research frameworks. A decade ago, Quarantelli (1993) compared findings on the
      similarities and differences between consensus- and conflict-type events by
      illustrating a conceptual distinction between the two. In this paper, this
      discussion is expanded to include terrorist attacks by offering comparisons from
      research findings following 11 September. We provide analyses of individual,
      organisational, and community-level behaviour in crisis situations and suggest
      how 11 September is both similar to, and differs from, consensus- and conflict
      type events as they were previously considered. Applications for emergency
      management are also suggested.

PMID- 14725091
TI  - Preparedness for emergency response: guidelines for the emergency planning
      process.
AB  - Especially since the terrorist attacks of 11 September 2001, governments
      worldwide have invested considerable resources in the writing of terrorism
      emergency response plans. Particularly in the United States, the federal
      government has created new homeland security organisations and urged state and
      local governments to draw up plans. This emphasis on the written plan tends to
      draw attention away from the process of planning itself and the original
      objective of achieving community emergency preparedness. This paper reviews the
      concepts of community preparedness and emergency planning, and their
      relationships with training, exercises and the written plan. A series of 10
      planning process guidelines are presented that draw upon the preparedness
      literature for natural and technological disasters, and can be applied to any
      environmental threat.

PMID- 14725092
TI  - [Editorial on the last issue of Swiss Surgery].

PMID- 14725093
TI  - [How often do surgical residents operate in a category A non-university post
      graduate teaching hospital?].
AB  - INTRODUCTION: After introduction of the new postgraduate training program for
      general surgery the completion of the operation list still represents the most
      important step. Based on our number of operations we examined whether residents
      would carry out the requested interventions at our non-university teaching
      hospital (category A). METHOD: For eight tracer operations we retrospectively
      counted the number of cases of the non private patients from 1998-2002 and took
      account of the postgraduate education status of the operator. In this period the
      team consisted of 51 residents (71 education years), of whom 18 candidates for
      general surgery who carried out the interventions (35 education years, inclusive
      rotation in ICU, emergency room and special surgical disciplines). RESULTS:
      Regarding all tracer operations, the amount of interventions per year and
      candidate which are necessary to accomplish the goal for the first four years of
      education are reached: appendectomy 8.9, laparoscopic cholecystectomy 7.3, open
      inguinal hernia repair 9.4, varicose veins operation 12.1, open colon sigmoideum
      resection 3.2, hip and malleolar fracture 6.9, hemithyreoidectomy 5. CONCLUSION:
      Completion of the operation list as the major training goal was reached at our
      institution. Following our structured education program the demands regarding
      postgraduate education will be met also in future. Further studies however, must
      examine the impact of the new resident's work contracts dictating a reduction of
      the weekly working hours.

PMID- 14725094
TI  - [5 years ATLS (Advanced Trauma Life Support) courses in Switzerland].
AB  - Five years ATLS (Advanced Trauma Life Support) in Switzerland are analysed, the
      problems are discussed and the changes during this period are demonstrated. ATLS
      Switzerland is a part of the Swiss surgical Society, introduced by the ATLS
      International Faculty in 1998. Switzerland with 4 official languages needs a
      special structure. For this reason a decentralisation of the courses was
      necessary with the need of five regional universities where ATLS courses are
      offered. Statistics of the rising amount of courses demonstrate the enormous rush
      for ATLS courses in our country. Three courses in 1998 where followed by six
      courses in 1999, up to 18 courses in 2002. 2001 was the first year with ATLS in
      the Swiss Army. Since 1.1.2003 Paul Martin Sutter, Biel ist the new National
      Director, successor of Domenic Scharplatz, Thusis.

PMID- 14725095
TI  - [Cost analysis of acute therapy of polytrauma patients].
AB  - The rising costs of the Swiss health care system are currently a source of
      discussion. Precise facts about the treatment costs in Switzerland are not
      available. The aim of this paper is to assess the price of the acute therapy of
      multiple trauma patients at the University Hospital of Zurich. We analysed the
      exact treatment costs of 16 patients with an average Injury Severity Score (ISS)
      of 33.9. All these cases had a private or a supplementary insurance coverage,
      were foreigners or were otherwise invoiced according to the so-called hospital
      tariff (Spitalleistungskatalog/SLK). We developed a concept to measure the
      expenditure not covered by the insurance of those with a basic insurance, who
      entail the largest percent of all hospitalized patients. The average amount
      invoiced was 128,135 Swiss Francs (31,266-310,358 CHF). After subtracting the
      profit, gained on cases charged according to the SLK, the remaining deficit per
      ordinary insured was 42-65% or 33,703-138,829 CHF The range of this amount
      depends on the insurance status of the afflicted person. If hospitals are
      required to work with a balanced budget, then these losses can no longer be
      neglected. New forms of invoicing multiply trauma patients must be found in
      Switzerland.

PMID- 14725096
TI  - [Osteosynthesis of combined radius head and capitulum humeri fractures with mini
      implants].
AB  - INTRODUCTION: Combined injuries of the capitellum humeri and the radial head are
      rare. Most of them show combined osteocartilaginous lesions and collateral
      ligament lesions. Recommendations for treatment of these fatal injuries of the
      elbow are missing. TYPE OF STUDY: Five cases were investigated in an
      retrospective analysis. The same approach was used for the osteocartilaginous
      lesion of the capitellum as well as the injury of the radial head. Internal
      fixation was done with mini-titanimplants, three of them combined with resorbable
      pins. PATIENTS AND METHODS: Between 1996-1999 five patients (four men, one woman)
      with combined injury of the radial head and the capitellum were stabilized. The
      average age was 34 years (31-40 years). All fractures were stabilized by a direct
      radial approach with 1.5 mm or 2.0 mm lag screws partly with resorbable pins. All
      patients were evaluated radiologically and clinically according to the Mayo-elbow
      performance score. RESULTS: All patients were personally examined after an
      average period of 12.8 month (8-24 month) by an independent investigator. 4/5
      patients were assessed for their satisfaction. No radiological signs of avascular
      necrosis of the capitellum or arthrosis were found. Three patients showed
      periarticular calcifications. The range of motion was averagely 124 degrees
      (extension 5-30 degrees, flexion 110-145 degrees), in three of five cases a
      secondary intervention for improvement of joint mobility was necessary. The Mayo
      elbow-performance score rated for 85 points in average (range 70-100 points).
      CONCLUSION: Direct screw fixation with mini-implants, eventually combined with
      resorbable pins allows to use the same approach for anatomic reconstruction and
      fixation of the capitellum humeri and radial head. Transarticular fragment
      fixation of the capitellum allows for safe compression. Therefore early
      functional rehabilitation is possible postoperatively. Secondary interventions
      for improve joint motion were necessary in three of five cases.

PMID- 14725097
TI  - Single hemicerclage for lateral type B malleolar fracture--a novel, minimal and
      reliable osteosynthesis.
AB  - AIM OF STUDY: To investigate the short- and long-term outcome of patients with
      isolated lateral malleolar fracture type B treated with a single hemicerclage out
      of metallic wire or PDS cord. METHODS: Over an 8-year period 97 patients were
      treated with a single hemicerclage for lateral malleolar fracture type B and 89
      were amenable to a follow-up after mean 39 months, including interview, clinical
      examination and X-ray controls. RESULTS: The median operation time was 35 minutes
      (range 15-85 min). X-ray controls within the first two postoperative days
      revealed an anatomical restoration of the upper ankle joint in all but one
      patient. The complication rate was 8%: hematoma (2 patients), wound infection
      (2), Sudeck's dystrophy (2) and deep vein thrombosis (1). Full weight-bearing was
      tolerated at median 6.0 weeks (range 2-26 weeks). No secondary displacement,
      delayed union or consecutive arthrosis of the upper ankle joint was observed. All
      but one patient had restored symmetric joint mobility. Ninety-seven percent of
      patients were satisfied or very satisfied with the outcome. Following bone
      healing, hemicerclage removal was necessary in 19% of osteosyntheses with
      metallic wire and in none with PDS cord. CONCLUSION: The single hemicerclage is a
      novel, simple and reliable osteosynthesis technique for isolated lateral type B
      malleolar fractures and may be considered as an alternative to the osteosynthesis
      procedures currently in use.

PMID- 14725098
TI  - Minimally invasive repair of pectus excavatum (MIRPE)--the Basel experience.
AB  - PURPOSE: Minimally invasive repair of pectus excavatum (MIRPE) was first reported
      in 1998 by D. Nuss. This technique has gained wide acceptance during the last 4-5
      years. In the meantime, some modifications of the technique have been introduced
      by different authors. Our retrospective study reports our own experience over the
      last 36 months and modifications introduced due to a number of complications.
      METHODS: From 3/2000 to 3/2003, 22 patients underwent MIRPE. Patients median age
      was 15.5 years (10.7 to 20.3 years). Standardised preoperative evaluation
      included 3D computerised tomography (CT) scan, pulmonary function tests, cardiac
      evaluation with electrocardiogram and echocardiography, and photo documentation.
      Indications for operation included at least two of the following: Haller CT index
      > 3.2, restrictive lung disease, cardiac compression, progression of the
      deformity and severe psychological alterations. RESULTS: In 22 patients (2 girls,
      20 boys) undergoing MIRPE procedure, a single bar was used in 21 patients and two
      bars in one boy. Lateral stabilisers were fixed with non resorbable sutures on
      both sides. Overall, postoperative complications occurred in six patients
      (27.3%). In two patients (9.1%) a redo-procedure was necessary due to bar
      displacement. An additional median skin incision was performed in two patients to
      elevate the sternum. Pneumothorax or hematothorax in two patients resulted in
      routine use of a chest tube on both sides. Long-term favourable results were
      noted in all patients. CONCLUSIONS: The MIRPE procedure is an effective method
      with elegant cosmetic results. Modifications of the original method help to
      decrease the complication rate and to accelerate acquirement of expertise.

PMID- 14725099
TI  - [The value of ultrasound diagnosis in "acute appendicitis" patient admission].
AB  - The rate of unnecessary appendectomy is frequently criticized. Today, sonography
      and CT-scan are helpful tools to minimize this rate. Which value has the
      ultrasonography in the decision making today? METHODS: Retrospective analysis of
      132 patients undergoing appendectomy in respect of sonography and rate of
      histologically confirmed appendicitis from 1.1.95-31.12.98. Prospective analysis
      of 99 patients admitted for acute appendicitis in respect of pre- and posttest
      probability (after sonography) by the responsible surgeon from 1.1.99-31.12.00.
      RESULTS: Retrospective part: 122/132 patients had an acute appendicitis (92%).
      Sonography was performed in 64% of the patients. There was only one wrongly
      positive sonography. Prospective part: 76/99 patients were operated on. 70/76 had
      an acute appendicitis (92%). Sonography was performed in 87%. Six patients
      presented a histologically normal appendix: In two of them no increase of the
      probability after sonography was noted, in three of them an slight increase of
      only 20%, and in one of them a decrease of 20% even. CONCLUSION: Sonography with
      a pre- and posttest-probability is recommended in clinically doubtful cases. In
      our experience the physician performing the sonography is almost always right.
      But the diagnosis of an acute appendicitis remains a combination of clinical and
      sonographic evaluation.

PMID- 14725100
TI  - [Intestinal perforation after preoperative colonic tattooing with India ink].
AB  - Since the ability to palpate the bowel is lost in laparoscopic colon surgery
      preoperative marking of lesions is required to avoid "blind" resection.
      Endoscopic tattooing with India ink is the agent of choice because of its
      simplicity and the long-lasting stain. Only few complications have been reported
      using this technique. We present a case with localized necrosis and
      retroperitoneal perforation after endoscopic tattooing. Due to the formation of a
      local inflammatoric pseudotumor laparoscopic resection was impossible and open
      right hemicolectomy was necessary. Fever, abdominal pain and signs of local
      peritonitis after endoscopic tattooing should remind clinicians of this rare
      complication.

PMID- 14725101
TI  - Peritoneal mesothelioma after environmental asbestos exposure.
AB  - Mesothelioma are primary malignant neoplasms of the serous membranes. They
      usually involve the pleura and rarely the pericardium, the peritoneum and the
      tunica vaginalis testis. About 90% are associated with exposure to asbestos. The
      exposure is generally occupational, an environmental inhalation of asbestos and
      asbestiform fibers in areas in Turkey has been observed and presents a major
      health problem. This report of a patient from Anatolia with peritoneal
      mesothelioma after environmental exposure outlines the importance of considering
      this pathology in the differential diagnosis of a Turkish patient presenting with
      ascites.

PMID- 14725102
TI  - [Agenesis of the gallbladder].
AB  - Isolated agenesis of the gallbladder (AG) is a rare anomaly. Twenty-three percent
      of the patients are symptomatic and present with right upper abdominal pain,
      nausea and fatty food intolerance. The condition is frequently mistaken with
      excluded or sclero-atrophic gallbladder, regardless of the imaging modality used.
      Consequently, AG leads often to unnecessary and potentially dangerous surgery.
      During laparoscopy, the absence of normal anatomical structures and the
      impossibility of pulling on the gallbladder to dissect the triangle of Callot
      represent an increased risk of iatrogenic injury to biliary or portal structures.
      The aim of this study is to discuss the pitfalls of the available radiological
      exams and the management of this rare condition. We describe two cases of AG,
      with a review of the literature. A high index of suspicion is necessary when
      interpreting the radiological images. In case of doubt, a MRI-cholangiography is
      mandatory. Because of possible inherited transmission, relatives with a history
      of biliary symptoms should be investigated, even when asymptomatic.

PMID- 14725103
TI  - New York hospital looks to Six Sigma for culture change.

PMID- 14725104
TI  - Transition to production-based pay not without bumps in road.
AB  - A plan set in motion at Henry Ford Medical Group to shift from a salary--to a
      production-based pay system for physicians is helping the organization to weather
      the bruising economic climate for health care providers.

PMID- 14725105
TI  - Sensors keep patients flowing smoothly at surgery center.
AB  - The typical outpatient surgery facility is a hard place to find anything. Staff
      members make hundreds of phone calls each day to determine where patients are,
      keep updated on surgeries, and track down specialized equipment. Each time a call
      is dialed, a colleague on the other end must stop what he or she is doing to
      answer. The phones in the new 60,000-square-foot surgical suite at Providence St.
      Vincent Medical Center don't get nearly as heavy a workout because the facility's
      automatic tracking system displays the location of each patient in real time.

PMID- 14725106
TI  - Improving discharge prediction helps move patients through facility.

PMID- 14725107
TI  - Working together: I.T. and evidence-based medicine.

PMID- 14725108
TI  - Consolidation: the year that wasn't.

PMID- 14725109
TI  - Various technologies at work on the chain gang.

PMID- 14725110
TI  - Provider is patient with mobility.

PMID- 14725111
TI  - Shopping for health care online.

PMID- 14725112
TI  - Readers' perspective. "By 2010 biometric security technology will be commonly
      used to protect patient information".

PMID- 14725113
TI  - IOM urges adoption of data standards as core of revamped health care system.

PMID- 14725114
TI  - AHRO announces new technology grant opportunities.

PMID- 14725115
TI  - USP finds different medication-error patterns in seniors.

PMID- 14725116
TI  - New drugs and dosage forms.

PMID- 14725117
TI  - Economic benefits of investigational drug services at an academic institution.
AB  - PURPOSE: The drug cost avoidance and revenue associated with the provision of
      investigational drug services (IDSs) at an academic institution were studied.
      METHODS: The study protocols and dispensing data for the investigational drug
      studies conducted at the institution over two fiscal years (2000-01 and 2001-02)
      were reviewed. Revenue generated was calculated for all studies, and drug cost
      avoidance was calculated for studies in which patients were likely to have been
      treated with active drug had they not been included in the study. RESULTS: Of 139
      studies in which the IDS was involved, 107 (77%) were eligible for the cost
      avoidance analysis. The total drug cost avoidance plus revenue over the two
      fiscal years was $5,300,428. The annualized drug cost avoidance plus revenue was
      $2.6 million. Cost avoidance varied with the type of study and the disease
      category involved. CONCLUSION: An IDS accounted for substantial drug cost
      avoidance over two fiscal years.

PMID- 14725118
TI  - Improving medication safety in a neonatal intensive care unit.
AB  - PURPOSE: A revision of the medication-use process intended to reduce errors on a
      neonatal intensive care unit (NICU) is described. SUMMARY: A multidisciplinary
      team conducted a systematic review and implemented multifaceted changes to
      improve the NICU's medication-use process. These changes were made to improve
      safety and consistency and make the system more user-friendly. A distinct, unit
      specific formulary was created for the drug products used on the NICU. Rules were
      built into the order-entry computer system for these NICU formulary items to
      identify doses outside the documented range on the basis of body weight. A unit
      specific reference was developed detailing all formulary mnemonics, oral drug
      compounding and i.v. admixture procedures, and guidelines for appropriate product
      selection. Emergency medication sheets listing the calculated doses by weight for
      critical or urgent medications were developed; these sheets are provided for
      every new admission and are updated weekly. End-product-testing procedures for
      i.v. admixtures and a medication-checking process for the unit's automated
      dispensing machine were implemented. CONCLUSION: Systematic changes in the
      medication-use process designed to reduce the opportunity for errors were
      implemented on an NICU.

PMID- 14725119
TI  - Stability and compatibility of reconstituted ertapenem with commonly used i.v.
      infusion and coinfusion solutions.
AB  - PURPOSE: The stability of ertapenem sodium in various commonly used i.v. infusion
      solutions and its compatibility with coinfusion solutions was studied. METHODS:
      Ertapenem was reconstituted with sterile water for injection and then diluted
      with various commercial i.v. infusion solutions to concentrations of 10 and 20
      mg/mL. The solutions were stored in flexible polyvinyl chloride containers at 4
      and 25 degrees C and in sterile glass vials at -20 degrees C. The drug's
      stability at 4 degrees C was monitored daily for up to 10 days, at 25 degrees C
      at appropriate hourly intervals for up to 30 hours, and at -20 degrees C. The
      daily for up to 14 days. Compatibility with the coinfusion solutions was
      monitored for up to eight hours at room temperature. Stability assays were
      conducted until the ertapenem concentration decreased by 10% or the corresponding
      degradation products exceeded the approved specifications. Ertapenem
      concentrations were determined by a stability-indicating high-performance liquid
      chromatography assay. RESULTS: Ertapenem was more stable in solutions stored at 4
      degrees C versus 25 degrees C. Samples frozen at -20 degrees C showed extreme
      variability. Ertapenem 10 mg/mL was stable for a longer time than at the 20-mg/mL
      concentration. Ertapenem demonstrated the greatest stability in 0.9% and 0.225%
      sodium chloride solutions. CONCLUSION: Ertapenem sodium injection 10 and 20 mg/mL
      are relatively stable in sodium chloride injections and Ringer's solution when
      stored at 25 and 4 degrees C, but are unstable in mannitol and dextrose
      solutions. The drug can be coinfused with hetastarch, heparin sodium, and
      potassium chloride over several hours.

PMID- 14725120
TI  - Improving information flow and documentation for clinical pharmacy services.

PMID- 14725121
TI  - Changes in renal function after changes in antifungal drug therapy.

PMID- 14725122
TI  - Stability of tramadol hydrochloride--acetaminophen (Ultracet) in strawberry syrup
      and in a sugar-free vehicle.

PMID- 14725123
TI  - Medication safety manager in an academic medical center.

PMID- 14725124
TI  - Clinical information management systems: an emerging data technology for
      inpatient pharmacies.

PMID- 14725125
TI  - Examining the value of pharmacy benefit management companies.

PMID- 14725126
TI  - Tenofovir: a nucleotide analogue reverse-transcriptase inhibitor for treatment of
      HIV infection.

PMID- 14725127
TI  - Documentation of smoking status in pharmacy dispensing software.

PMID- 14725128
TI  - [Choanal atresia: therapeutic management and results in a series of 58 children].
AB  - INTRODUCTION: An error of table being slipped during the publication of this
      article in number 1 (2003), the Review republishes it in entirety for a better
      comprehension. The preceding reference must be replaced by this one: Rev Laryngol
      Otol Rhinol 2003;124,3:139-143. OBJECTIVES: To assess and compare long term
      results after surgical correction (transnasal or transpalatine approaches) of
      unilateral or bilateral choanal atresia, in children with or without associated
      anomalies. PATIENTS: During a 13-year period, 58 children were included in this
      retrospective study. Seventy-five choanas were operated on (41 unilateral and 17
      bilateral). The transpalatine approach was performed in 41 children (56 choanas)
      while the transnasal approach was performed in 17 patients (19 choanas).
      Associated anomalies were reported in 28 children and corresponded to CHARGE
      association in 13 cases. RESULTS: With a mean follow-up of 7 years, perfect
      choanal permeability was reported in 90% of children operated on through a
      transpalatine approach and in 76% of children with a transnasal approach. A
      complementary therapeutic procedure was required in 54% of transpalatine
      approaches and 46% of transnasal approaches to yield these results. Postoperative
      choanal permeability was obtained in 93% of children without an associated
      anomaly and in 77% of those with associated anomalies, such as in 88% of
      unilateral atresias and 80% of bilateral ones. CONCLUSION: Initial success rate
      after surgery is similar for all surgical procedure insofar as nearly half
      choanas required a complementary therapeutic procedure. The endonasal procedure
      using the microdebrider appears hopeful and the KTP laser is interesting in
      fibrous residual stenosis. Associated anomalies are factors which lower general
      prognosis while inducing a higher surgical failure rate.

PMID- 14725129
TI  - Paediatric endoscopic sinus surgery (PESS): review of the indications.
AB  - Functional endoscopic sinus surgery (FESS) differs in children and adults. The
      purpose of this article is to highlight the differences by focusing on the
      anatomical landmarks and diagnostic and surgical peculiarities present in
      children. We review the indications of FESS in children, partially based on our
      personal experience, in order to establish a list of relative and absolute
      indications for the procedure. We also discuss controversies such as the overuse
      of FESS for chronic sinusitis and the potential postoperative alterations of
      pneumatization. The paper includes a retrospective study of our results with
      endoscopic dacryocystorhinostomy (DCR) in 31 children and the endoscopic removal
      of 11 juvenile angiofibromas. All patients were reviewed in the out patients
      clinic. Patency of DCR was evaluated by fluorescein dye application to the
      conjunctiva, endoscopy with a 2.7 mm rigid endoscope or by means of clinical
      parameters, such as tearing or recurrent dacryocystitis. For patients operated on
      for a juvenile angiofibroma endoscopy of the nose and MRI every 6 months for the
      first two years were scheduled. Functional outcome showed good overall results in
      90.3% of DCR after primary surgery. The endoscopic approach to juvenile
      angiofibromas achieved a cure rate of 90.9% after a follow-up of at least 24
      months.

PMID- 14725131
TI  - [Intraorbital infected cyst in the adult].
AB  - Orbital dermoid cyst is a rare tumour, whose pathogenesis remains unclear. This
      is a childhood pathology. It is usually located in the lateral orbit. This tumour
      is rarely observed during adulthood, and complications are often responsible for
      the symptomatology. We present a new case with late presentation and because of
      its variety, a review of the literature.

PMID- 14725130
TI  - [Multifactorial analysis of preoperative functional symptoms in nasal polyposis
      (report of 403 patients)].
AB  - PURPOSE: Nasal polyposis is an invading disease whose evolution is dominated by
      functional symptoms. The aim of this study was to evaluate in cortico-resistant
      patients with nasal polyps the pre-operative functional symptoms in order to
      define factors that might increase them. METHODS: 403 patients were included in
      this study. All of them met the inclusion criteria of follow-up and initial
      examination. Anosmia, pain, nasal obstruction, rhinorrhea and sneezing were
      evaluated by patients themselves. Radiological data, respiratory function test
      results and histological data were matched. RESULTS: In our series, functional
      symptoms were dominated by anosmia, nasal obstruction and rhinorrhea. Pain and
      sneezing appeared to be less frequent. Analysis of co-variables allowed us to
      define factors which increased pre-operative functional symptoms. Some of them
      are well known (such as Fernand-Widal triad or stage 3 nasal polyposis), while
      others appear new or surprising. The same is true for frontal sinus involvement
      on CT-scan and glandular hyperplasia on histological study. CONCLUSION: Analysis
      of the complete clinical, radiological and histological picture has allowed us to
      emphasise the importance of certain factors on the functional symptoms of 403
      patients with polyps of the nose and sinuses, resistant to steroid treatment. The
      same is true for Widal's disease, for a higher endoscopic grading, for frontal
      sinus involvement, and for histological evidence of glandular hyperplasia.

PMID- 14725132
TI  - [Combined approach (endoscopic and external) for the treatment of sinusal
      mucoceles].
AB  - AIM OF THE STUDY: Determination of the best surgical approach in the treatment of
      mucocoeles of the sinuses according to their localization. PATIENTS AND METHODS:
      A retrospective study has been carried out including forty three cases of sinus
      mucocoeles, surgically treated from 1990 to 1997. These were in descending order,
      frontal (n = 19), maxillary (n = 10), ethmoido-frontal (n = 9), sphenoidal (n =
      3) and ethmoidal (n = 2). Surgical treatment was achieved with an exclusive
      endoscopic approach in 28 cases whereas 15 of them underwent endoscopic surgery
      associated with an external approach (also called combined technique). Short term
      complications and recurrence were recorded after a minimum of 6 years follow-up,
      according to the type of surgery performed and the topography of the mucocoele.
      RESULTS: Recurrence of mucocoeles is prevented in 95.8% of cases by an exclusive
      endoscopic treatment in ethmoido-frontal, maxillary, sphenoidal and ethmoidal
      sites. On the other hand, the recurrence rate in mucocoeles involving the frontal
      sinuses without ethmoidal involvement, was significantly higher when the
      mucocoele was operated on by an exclusively endoscopic method (25%, p < 0.001)
      rather than by a combined technique (0%). DISCUSSION AND CONCLUSION: Ethmoido
      frontal, maxillary, sphenoidal and ethmoidal mucocoeles are excellent indications
      for an exclusively endoscopic endonasal surgery. An external approach, combined
      with endoscopic surgery, is suitable in frontal mucocoeles, especially in distal
      sites and in case of recurrence.

PMID- 14725133
TI  - Cleft palate and otitis media with effusion: a review.
AB  - Otitis media with effusion is a common finding in children with cleft palate.
      However, although middle ear effusions have been reported to be almost universal
      among infants with cleft palate, less is known regarding the epidemiology,
      natural history, and outcome of middle ear disease among older children with
      cleft palate. Furthermore, considerable controversy surrounds the management of
      otitis media with effusion in these children: many authors have advocated a
      policy of early or scheduled ventilation tube insertion on account of the high
      incidence of hearing loss and speech difficulties; others have advocated a more
      conservative policy on account of the high incidence of complications from
      ventilation tubes and lack of evidence supporting a policy of early intervention.
      In the present paper, we review the epidemiology, aetiology, and natural history
      of middle ear disease in children with cleft palate. We also discuss the
      controversies involved in the management of these patients.

PMID- 14725134
TI  - Time-intensity trade of bilaterally bone-conducted sounds in normal hearing
      subjects.
AB  - OBJECTIVE AND METHODS: In an effort to examine the rules by which information of
      bilaterally applied bone-conducted signals arising from interaural time
      differences (ITD) and interaural intensity differences (IID) is combined, data
      were measured for continuous 500 Hz narrow-band noise at 60 dBHL in 30 normal
      hearing subjects using a centering method. Time-intensity trading functions were
      obtained by means of a sound image shifted towards one side by presenting an ITD,
      and shifted back to a centered sound image by varying the IID in the same ear.
      ITD values were varied from -600 to +600 microseconds at 200 microseconds steps,
      where negative values indicate delays to the right ear. RESULTS: Time-intensity
      trading functions in response to bone-conducted signals showed significantly
      lower discrimination thresholds across IIDs, when compared to a control group
      with applied air-conducted signals. These findings can be interpreted as a
      constructive interference effect related to the intimate mechanism of bilateral
      bone conduction, where interaural time differences play a major role. CONCLUSION:
      Time-intensity trade of bilaterally bone-conducted sounds in normal-hearing
      subjects is the highly sensitive. The high speed of sound through the skull may
      be the main reason for the high sensitivity of time-intensity trading.

PMID- 14725135
TI  - The use of speech therapy in the treatment of globus pharyngeus patients. A
      randomised controlled trial.
AB  - INTRODUCTION: Globus sensation is a common condition accounting for about 4% of
      new referrals to an ENT clinic. A review of current theories on the cause of
      globus sensation concludes that no single aetiology is responsible. Wareing et al
      believed that globus sensation might in part be associated with excessive
      laryngeal and pharyngeal tension. The aim of this study was to substantiate in a
      controlled prospective manner the results of a non-controlled study by the same
      authors that certain speech therapy techniques improved globus symptoms. METHODS:
      1. 36 patients with typical globus pharyngeus symptoms were randomised to
      treatment with speech therapy (Study group) and reassurance by nurse practitioner
      (Control group). The following data was collated for each patient: duration and
      type of globus symptoms (sense of a lump in the throat/throat irritation),
      severity of globus symptoms on a visual analogue scale, fibreoptic laryngoscopy,
      full blood count, barium swallow. 2. At the end of 3 months, patients in both
      groups marked on the visual analogue scale the severity of their symptoms.
      RESULTS: There was a significant improvement in the globus symptom scores in the
      speech therapy group compared to pre-intervention scores (p < 0.001, Wilcoxon
      rank test). There was also a significant improvement in globus symptoms in the
      speech therapy group compared to controls (p < 0.001, Mann-Whitney U test).
      CONCLUSION: Initial results suggest that patients with globus pharyngeus symptoms
      benefit from speech therapy.

PMID- 14725136
TI  - Dysphonia and cervical hyperostosis: a case report.
AB  - We report a case of a 77-year-old man with a 3-year-history of progressive
      dysphonia, without dysphagia. His voice sounded breathy; the pitch and the
      loudness were low. He complained of a few episodes of voice breaking. At
      laryngostroboscopy the adduction motion of the left true vocal cord was slower
      than the contralateral one. A cervical spine X-ray demonstrated a generalized
      vertebral osteophytosis and a 3-centimeter-long anterior osteophytic spur,
      originating from C6. Evaluation with barium swallow showed a dislocation of the
      inferior cervico-oesophagus to the right, with a preservation of its lumen.
      Cervical-thoracic computed tomography showed a mild pressure produced by the
      osteophyte on the thyroid cartilage and the presence of the radiological criteria
      for Forestier's disease. Therefore, the presence of dysphonia in older adults
      without any primary laryngeal cause, indicates a radiological study of the
      cervical-thoracic region, in order to discover cervical osteophytosis.

PMID- 14725137
TI  - [Spontaneous cervical emphysema: a case report].
AB  - Spontaneous cervical subcutaneous emphysema, without any aetiology found in the
      clinical history, is far less common than subcutaneous cervical emphysema
      following trauma, surgery, or infectious cervical processes. In this recent case
      report, the authors describe a young woman who developed a cervical subcutaneous
      emphysema. No responsible factor had been found. Radiological investigations
      revealed a pneumomediastinum, which is an uncommon but a serious complication of
      cervical emphysema. The CT-scan highlighted a rupture of the crico-thyroid
      membrane, from which the air had followed the fascial planes up to the neck and
      the mediastinum. The authors describe the treatment and clinical course. They put
      forward an embryological hypothesis regarding the spontaneous crico-thyroid
      membrane rupture. A congenital fragility of this area could exist which could
      explain its breach. The pathogenesis and management of spontaneous cervical
      emphysema are discussed in the light of diverses articles about this subject. The
      radiological or surgical explorations which may be used in this aetiological
      diagnosis and treatment are given.

PMID- 14725138
TI  - [Subcutaneous emphysema and pneumomediastinum after dental drilling].
AB  - Subcutaneous emphysema and pneumomediastinum is a rare complication of dental
      treatment. Our case report describes a case secondary to dental drilling with a
      high-speed air drill, and diffusion of the compressed air. Our case had the
      classical clinical features of sudden subcutaneous emphysema starting in the
      face, and subsequently extending into the neck and thorax, accompanied by severe
      pain and dyspnoea. Rapid medical treatment for this emergency avoided the
      surgical decompression.

PMID- 14725139
TI  - [The pedicled musculo-cutaneous latissimus dorsi flap].
AB  - The pedicled musculo-cutaneous latissimus dorsi flap presents many advantages and
      merits to be used more frequently in head and neck surgery because a large
      musculo-cutaneous pallet with an excellent vitality can be obtained. The flap
      reaches easily the inferior third of the face thanks to its rotation arc, leading
      to a discreet aesthetic scar. For this reason, its use is interesting especially
      for women. The aim of this article is to focus on the fundamental points of the
      technique we use and to emphasize the importance of the postoperative patient's
      arm positions to obtain a good result.

PMID- 14725140
TI  - Profile of an invaluable colleague: Lisa Goulet, nurse clinician for organ and
      tissue donation.
AB  - Lis Goulet is the Nurse Clinician for Organ and Tissue Donation at the McGill
      University Health Centre (MUHC). She was the first nurse in Quebec to be
      appointed to such a position. She is not only a pioneer in this clinical area,
      but also an inspiration to others and a guide for those who are following in her
      footsteps. As colleagues, we wish to acknowledge her many contributions which
      include the challenges she has met, the hurdles she has to overcome, and the
      inroads she has made to the Organ and Tissue Donation Program at the MUHC.

PMID- 14725141
TI  - Review of laryngospasm and noncardiogenic pulmonary edema.
AB  - Laryngospasm is an emergency situation that requires rapid identification and
      resolution of the obstructed glottis. Although there is a low incidence of
      laryngospasm, it is important to remember that any patient has the potential for
      post-extubation laryngospasm. Nurses must know about the causes, risk factors and
      treatment for this respiratory emergency. This includes the plan of care and
      possible medications administered to assist in restoring the patient's airway.
      Nurses must be able to respond quickly to avoid complications such as
      noncardiogenic pulmonary edema (NCPE) and respiratory arrest. The triggers, signs
      and symptoms, and treatment of NCPE are also reviewed. Due to the risk of
      laryngospasm recurring or NCPE presenting itself, any patient who has had
      laryngospasm needs close monitoring for two to three hours after the laryngospasm
      has resolved. It is important for nurses to review the interventions for
      laryngospasm and NCPE prior to caring for a patient with this respiratory
      emergency.

PMID- 14725142
TI  - Timing of hemodynamic pressure measurements on derived hemodynamic parameters.
AB  - The purpose of this study was to examine the difference between hemodynamic
      pressures and parameters obtained pre- compared to post-thermodilution CO
      measurements. A repeated measures within subject design was conducted with a
      cardiac surgical cohort. Three measures of hemodynamic pressures and parameters
      were determined pre- and post-CO measurements (Set 1) and repeated in 30 minutes
      (Set 2). The sequence was duplicated in four hours (Sets 3 and 4). Hemodynamic
      pressures lower pre-CO were PAS at Sets 1 and 3, and SBP, DBP, and MAP at Set 3.
      Hemodynamic parameters lower pre-CO were PVRI at Set 1 and SVRI at Set 3. These
      pre-post CO differences did not vary by greater than 10%. As the CO injectate
      volume had minimal effect, hemodynamic pressures may be obtained pre- or post-CO
      to derive hemodynamic parameters.

PMID- 14725144
TI  - Making an impact.

PMID- 14725143
TI  - Evacuation of a critical care unit.
AB  - Emergency preparedness is crucial to the frontline nurse who provides patient
      care 24 hours a day, seven days a week, especially in the wake of the September
      11 bombing of the World Trade Centre (9/11). It is the professional
      responsibility of both the organization and the nursing staff to ensure that
      knowledge about disaster procedures is adequate. Disasters do not necessarily
      occur when the majority of administrative and support staff are on duty. It is
      imperative that nurses are informed of disaster procedures and can provide
      leadership during a crisis. In this article, the author discusses a Code Red
      (fire) with Code Green potential and actual Code Green (evacuation) two days
      later, of a 20-bed critical care unit.

PMID- 14725145
TI  - Nursing--the Christmas profession.

PMID- 14725146
TI  - Differentiating the three D's: delirium, dementia, and depression.
AB  - Confusion often presents a challenge to nurses caring for older adults. Three
      common states that result in confusion are delirium, dementia, and depression.
      The three conditions are compared and contrasted in this article.

PMID- 14725147
TI  - Exploring measures of functional dependence in the older adult with cancer.
AB  - An aging population and increased incidence of cancer in older adults indicate
      the need to assess functional status within cancer treatment planning. This type
      of assessment could affect decisions about treatment options, nursing
      interventions, and community services for elders with cancer.

PMID- 14725148
TI  - Managing organ-threatening systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a chronic, usually life-long, and potentially
      fatal autoimmune musculoskeletal condition. The involvement of the heart, lungs,
      kidneys, and central nervous system, and hematologic complications increase
      morbidity and mortality. Consequently, the medical-surgical nurse must understand
      the disease process and treatment modalities when assessing and developing a plan
      of care for the patient and family.

PMID- 14725149
TI  - They're real and they're here: the new federally regulated privacy rules under
      HIPAA.
AB  - The purpose of the HIPAA Privacy Rules was to create national standards to
      protect the privacy of personal health information. As of April 14, 2003, all
      covered health care entities must comply with the newly implemented national
      standards. The importance of staying updated with the law, while particularly
      important for the patient's privacy, is just as important for the nurse to avoid
      civil punitive damages and possible criminal charges.

PMID- 14725151
TI  - Relationship between nurse caring and patient satisfaction in patients undergoing
      invasive cardiac procedures.
AB  - Cardiac patients (N = 73) undergoing interventional cardiology studies reported
      perceptions of nurse caring and patient satisfaction with care. A moderately
      strong relationship (r = 0.53, p = 0.01) between caring and satisfaction was
      found. Male and female subjects did not differ on perceptions of caring and
      patient satisfaction. Since caring is considered fundamental to the nature of
      nursing, practicing nurses must appreciate its connection to outcomes, such as
      patient satisfaction.

PMID- 14725150
TI  - Genetics of hearing loss.
AB  - Advances in genetic technology have increased the knowledge of hereditary hearing
      loss in all age groups. A basic understanding of the multiple types and causes of
      hearing loss can advance nurses' ability to provide better education and referral
      services for their patients.

PMID- 14725152
TI  - The dirty bomb: management of victims of radiological weapons.
AB  - A "dirty bomb," a conventional explosive packed with radioactive material, kills
      or injures through the initial blast and by airborne radiation and contamination.
      Adult-health nurses need an understanding of the consequences of blast injuries
      and radiation exposure, and the management of victims.

PMID- 14725153
TI  - The ABCs of DVT.

PMID- 14725154
TI  - Lantus: a new insulin.

PMID- 14725155
TI  - Healing interactions.

PMID- 14725156
TI  - Laboratory studies in the evaluation of urologic disease: Part I.
AB  - This is the first of a two-part article reviewing basic laboratory, imaging,
      endoscopic, urodynamic, and miscellaneous studies used for screening and
      diagnosis of urologic disease. Normal values, recommended collection procedures,
      and interpretation of results are also reviewed. This initial installment deals
      with laboratory tests used in urologic disease.

PMID- 14725157
TI  - Diagnostic tests and tools in the evaluation of urologic disease: Part II.
AB  - This is the second of a two-part article reviewing basic laboratory, imaging,
      endoscopic, urodynamic, and miscellaneous studies used for screening and
      diagnosis of urologic disease. Part one dealt with laboratory analysis. This
      installment deals with diagnostic tests and tools used in urologic disease.

PMID- 14725158
TI  - Promoting social continence: products and devices in the management of urinary
      incontinence.
AB  - Urinary incontinence (UI) is a prevalent problem occurring in men and women
      across the lifespan. Technologic innovations have provided individuals with
      incontinence and caregivers with an array of options for achieving social
      continence. Even when UI cannot be completely cured, it can always be managed
      with products, skin care regimens, occlusive or drainage devices and toileting
      equipment to ensure optimal skin integrity, odorless urine containment, social
      independence, comfort, and freedom of movement. Various products, devices, and
      equipment available to help incontinent individuals preserve independence and
      quality of life and manage incontinence are described.

PMID- 14725159
TI  - Pyuria detection using a dipstick applied to urine in incontinence pads.
AB  - The purpose of this study was to determine whether pressing a dipstick into a pad
      within 2 hours of urine saturation detected pyuria as effectively as immersing a
      dipstick in a urine specimen. Sensitivity, specificity, and positive and negative
      predictive values indicated that results of the pad method were as effective as
      those of direct dipstick into clean-catch urine in detecting pyuria. In the
      elderly, sensitivity of the pad method was 100%, indicating this would be an
      effective method for initial assessment of pyuria.

PMID- 14725160
TI  - Urgent urological management of the paraplegic/quadriplegic patient.
AB  - Individuals who have become paraplegic or quadriplegic as a result of trauma,
      disease, or surgery can offer a challenge to any member of the health care team
      when it comes to the treatment of medical conditions. Some urological conditions
      may precipitate an episode of autonomic dysreflexia, which is a syndrome that
      usually affects individuals with a spinal cord injury above T6. Having the
      necessary knowledge and experience to deal with this patient population can bring
      a welcomed sense of relief to patients who present to the emergency department
      with an urgent urological condition.

PMID- 14725161
TI  - Lifestyle changes to prevent BPH: heart healthy = prostate healthy.
AB  - Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions found
      in men, and increases with age. Drug, surgical, and phytotherapy tend to dominate
      the medical literature when discussing potential treatments for this condition.
      These treatments have demonstrated remarkable effectiveness for the various
      degrees of BPH. However, the potential for lifestyle changes to actually prevent
      this disease or reduce the severity of this condition when used as an adjunct to
      conventional treatment is not only intriguing but is strongly supported by past
      limited studies. More research is needed, but the time is ripe to discuss with
      patients the potential lifestyle changes that could influence risk. Obesity, a
      lack of physical activity, dyslipidemia, diabetes, hypertension, a heart
      unhealthy diet, and other factors may significantly increase the risk of BPH.
      Patients should be told that factors that increase the risk of cardiovascular
      disease seem to be associated with an increased risk of BPH or a greater severity
      of BPH.

PMID- 14725162
TI  - Update on influenza (the flu).

PMID- 14725163
TI  - The joys of aging.

PMID- 14725164
TI  - Designing clinical research studies: Part II.
AB  - The focus of this article has been to describe common sampling strategies,
      determine how to decide sample size, consider the three hallmarks of an
      intervention study, and to describe what should be included in the procedures of
      the methods section of the study. An effort was made to emphasize material
      necessary for beginning investigators who would be designing small quantitative
      clinical studies. Resources are provided for further clarification and
      amplification.

PMID- 14725165
TI  - [The passion of nursing is challenged by a greater humanism. The Second
      International Congress of French Nurses, Montpellier, 2003].

PMID- 14725166
TI  - [The post-colonial theoretical approach in cultural nursing research about
      adapting nursing care to non-Western populations].
AB  - Providing culturally competent care to non-Western populations remains a
      challenge in Western pluralist societies. Limitations related to the use of
      cultural theories to adapt nursing care have to be acknowledged. Cultural
      theories erase the impact of the larger social context on non-Western
      populations' health. Health problems arising from social inequities have to be
      addressed, if culturally adapted nursing interventions, are to be designed. To
      this end, post-colonialist theoretical approach represents a promising avenue
      since it is aimed at unmasking health problems intersecting with race, ethnicity,
      gender, and social classes. Research endeavours are directed at integrating
      marginalized knowledge in nursing theorization. As well, post-colonialism, from
      which the concept of cultural safety is derived, is a means to enhance the
      quality of care offered by nurses coming from dominant ethnic group to non
      Western populations.

PMID- 14725167
TI  - [Approach to the concept of admission, between banality and complexity].

PMID- 14725168
TI  - [Social support contribution to health and the adoption and maintenance of health
      behaviors].
AB  - Social support refers to the presence of individuals providing emotional or
      material resources. Its four components are: integration, structure, function,
      and quality. This article presents empirical and theoretical data, as well as
      criticism of studies which examine the relationship between social support,
      global health and cardiovascular health, also evaluating direct or moderating
      contributions to the adoption and maintenance of health behaviours in persons
      with cardiovascular disease. Concrete implications for nursing practice are
      reviewed.

PMID- 14725169
TI  - [Health education of mothers during the postpartum period in the maternity
      services of Geneva].

PMID- 14725170
TI  - [Knowledge, technique and the nurse...].
AB  - The relationships maintained between treatment practices and theoretical
      knowledge of nursing techniques can be clarified by an analysis of treatment in
      general. Commencing from a reassessment regarding the treatment and structure of
      the theoretical knowledge concerned, the author proposes a systematic distinction
      between knowledge and practical technique. This distinction would permit the
      establishment of two distinct research domains: fundamental research and
      practical research.

PMID- 14725171
TI  - [Palliative care network and the elderly: what autonomy do they have?].
AB  - Several Swiss institutions of a socio-sanitary region have put together a network
      with the view of assuring efficient palliative care. A research was conducted in
      partnership with four health-care establishments in order to verify if the
      concept of autonomy conceived by professionals corresponded to the patients'
      needs. Semi-directive interviews were conducted, along with questionnaires. The
      analysis showed a considerable disparity between palliative philosophy and the
      real needs of elderly patients. The aging process experienced by the people
      interviewed was synonymous with illness, loss, suffering and quality of life are
      associated with youth. The dimension of the projects and partnerships is
      difficult for them to imagine.

PMID- 14725172
TI  - The complexities of health promotion.

PMID- 14725173
TI  - Health care communication issues in multiple sclerosis: an interpretive
      description.
AB  - Communication between persons with chronic illness and their professional health
      care providers is a critical element of appropriate health care. As the field of
      health care communication evolves, it becomes apparent that aspects of the
      illness experience shared by those affected by specific diseases might be a
      source of particular insight into what constitutes effective or appropriate
      communications. This interpretive description of health care communication issues
      in multiple sclerosis was based on qualitative secondary analysis of a set of in
      depth interviews and focus groups conducted with 12 persons with longstanding MS
      experience. Analysis of their accounts illustrates an intricate interplay between
      common features within the disease trajectory and the communications that are
      perceived as helpful or unhelpful to living well with this chronic illness. From
      the analysis of these findings, the authors draw interpretations regarding what
      might be considered communication competencies for those who care for patients
      with this disease.

PMID- 14725174
TI  - "Here's what I'd do...": condom promotion strategies proposed by high-risk women
      in Anchorage, Alaska.
AB  - Women drug users are at significant risk of sexually transmitted HIV; however,
      interventions aimed at increasing condom use by this population have been
      relatively ineffective. The authors conducted a series of focus groups with 17
      current and former drug-using women to identify (a) reasons for using versus not
      using condoms, (b) intervention strategies they believed would be most effective
      at increasing condom use, and (c) previous ineffective intervention strategies.
      Risk of HIV, sexually transmitted diseases, and pregnancy was the main reason
      given for using condoms. Many factors were identified that limited condom use,
      including lack of availability, substance use, and cost. Participants
      enthusiastically endorsed condom availability and AIDS awareness interventions,
      and suggested that no intervention was a waste of money. The authors discuss the
      limitations of the suggested interventions and recommend additional research to
      evaluate the efficacy of these strategies.

PMID- 14725175
TI  - Facilitators and challenges to organizational capacity building in heart health
      promotion.
AB  - The authors describe the facilitators and challenges to a multi-sectoral
      initiative aiming at building organizational capacity for heart health promotion
      in Nova Scotia, Canada. The research process was guided by participatory action
      research. The study included 21 organizations from diverse sectors. Participant
      selection for the data collection was purposive. The authors collected data
      through organizational reflection logs and one-to-one semistructured interviews
      and used grounded theory techniques for the data analyses. Factors influencing
      organizational capacity for heart health promotion varied, depending on the
      project stage. Nonetheless, leadership, organizational readiness, congruence,
      research activities, technical supports, and partnerships were essential to
      capacity-building efforts. Approaches to organizational capacity building should
      be multi-leveled, because organizations are influenced by multiple social systems
      that are not all equally supportive of capacity.

PMID- 14725176
TI  - Surfacing the life phases of a mental health support group.
AB  - Support groups have increased rapidly in number and become a viable alternative
      to formal treatment in the United States. However, little is known regarding how
      mental health advocacy or support groups start and develop, or about challenges
      that can threaten their survival. In this 2 1/2-year ethnography, the author
      studied the culture of a developing family support program associated with a
      system of care. Several phases emerged, reflecting an organizational dynamic. The
      group dynamics and response to challenges have implications for organizers and
      parent organizations about the need for technical assistance necessary for
      survival of the group. Participant observation and immersion in the culture of
      such groups can provide a deeper understanding of the ideologies and values
      around which they organize and the kinds of tensions that members can experience
      during the group's cycle.

PMID- 14725177
TI  - Intersections of gender and age in health care: adapting autonomy and
      confidentiality for the adolescent girl.
AB  - Autonomy and confidentiality are central topics in adolescent health care, both
      pertaining to findings that nonparent adults often benefit adolescent girls'
      psychological resilience. Traditionally, autonomy captures a patient's right to
      self-determine a course of treatment, whereas confidentiality is understood as
      privacy between doctor and patient. The author proposes a revision of these
      constructs to accommodate the psychology of adolescent girls in health care
      contexts through a case study of a 17-year-old girl's hospitalization. In
      particular, the importance of voice and trust in girls' psychology calls for
      understanding autonomy as self in relationship and confidentiality as mutual
      confidence. Suggestions for practice are guided by the premise that girls' health
      care can foster psychological risk or resilience, depending on the doctor-patient
      relationship.

PMID- 14725178
TI  - Know when to hold 'em, know when to fold 'em: qualitative thinking outside the
      university.
AB  - Qualitative researchers often face a dilemma. They are asked to apply their
      knowledge to problems without adequate time or support to conduct projects that
      meet traditional academic standards of research design and methodology. Should
      qualitative researchers pitch in and get involved or keep their distance? What
      can they hope to accomplish, if anything? How do they know whether a particular
      job can be done? Traditional research training provides few guidelines to answer
      such questions. In this article, the author explores one way to think about what
      such guidelines might look like.

PMID- 14725179
TI  - Improving accuracy of transcripts in qualitative research.
AB  - Everyone who has worked with qualitative interview data has run into problems
      with transcription error, even if they do the transcribing themselves. A
      thoughtful, accurate, reliable, multilingual transcriptionist with a quick
      turnaround time is worth her or his weight in gold. In this article, the authors
      examine some transcription circumstances that seem to bring about their own
      consistent set of problems. Based on their experiences, the authors examine the
      following issues: use of voice recognition systems; notation choices; processing
      and active listening versus touch typing; transcriptionist effect; emotionally
      loaded audiotaped material; class and/or cultural differences among interviewee,
      interviewer, and transcriptionist; and some errors that arise when working in a
      second language. The authors offer suggestions for working with transcriptionists
      as part of the qualitative research team.

PMID- 14725180
TI  - Ethical dilemmas in research on Internet communities.
AB  - There has been a rapid growth in the number of articles using Internet data
      sources to illuminate health behavior. However, little has been written about the
      ethical considerations of online research, especially studies involving data from
      Internet discussion boards. Guidelines are needed to ensure ethical conduct. In
      this article, the authors examine how a youth-focused research program negotiated
      ethical practices in the creation of its comprehensive health site and online
      message board. They address three situations in which ethical predicaments arose:
      (a) enrolling research participants, (b) protecting participants from risk or
      harm, and (c) linking public and private data. Drawing on the ethical principles
      of autonomy, nonmaleficence, justice, and beneficence, the authors present
      practical guidelines for resolving ethical dilemmas in research on Internet
      communities.

PMID- 14725181
TI  - Involvement and detachment in researching sexuality: reflections on the process
      of semistructured interviewing.
AB  - In this article, the authors reflect on the utility of the concept of involvement
      detachment for researchers involved in a study of the lifeworlds of gay, lesbian,
      and bisexual young people where one of the researchers was lesbian. They focus in
      particular on the process of semistructured interviewing in qualitative research
      and the analysis of material generated by the interviews, noting that complete
      detachment from the subject of study is neither achievable nor desirable. They
      discuss the benefit of teamwork in supporting researchers and enhancing the
      integrity of the research, particularly when the subject is sensitive, the
      importance of researchers' active management of their own ideological leanings,
      and the understanding of project management as a conceptual and cognitive process
      that is fundamental to enhancing research rigor.

PMID- 14725182
TI  - Vector-borne diseases in humans and animals: activities of the Swiss Tropical
      Institute and risks for Switzerland.
AB  - The recent outbreak of anaplasmosis in a Swiss cattle herd triggered a discussion
      of the risk of vector-borne diseases in animals and humans in relation to climate
      changes and other factors. This overview presents the Swiss Tropical Institute's
      (STI) activities on vector-borne diseases (malaria, trypanosomosis, and
      leishmaniosis in humans and tick-borne diseases in livestock), describes the
      possible risks for humans and animals in Switzerland, and discusses options for
      action in the domains of public health, livestock production and companion
      animals. Switzerland is increasingly confronted with vector-borne diseases in
      humans and animals, but this is mainly due to an increase in imported cases. The
      emergence of a disease in one sector (human or veterinary medicine) may predict
      future trends in the other. A stronger intersectoral collaboration between public
      health and veterinary institutions at the federal and cantonal level is needed.

PMID- 14725183
TI  - [Current data on antibiotic resistance of the most important bovine mastitis
      pathogens in Switzerland].
AB  - 100 strains of Staphylococcus aureus (S. aureus), 100 strains of coagulase
      negative staphylococci (CNS), 100 strains of Streptococcus spp. and 100 strains
      of Escherichia coli (E. coli), isolated from bovine mastitis milk samples between
      November 2002 and April 2003, were tested for their sensitivity to various
      antibiotics by means of the agar diffusion method. The antibiotics were chosen on
      the basis of their licenses for intramammary application in Switzerland
      (www.vetpharm.unizh.ch). 91% of the S. aureus strains were sensitive to all the
      antibiotics tested. Only 9% of the strains were resistant to Penicillin G and 7%
      to Ampicillin. 53% of the CNS strains were sensitive to all the antibiotics
      tested. 31% exhibited resistance to Penicillin G, 26% to Ampicillin, 16% to
      Cloxacillin and 14% to Lincomycin. 30% of the Streptococcus spp. strains were
      sensitive to all the antibiotics tested. 4% were resistant to Penicillin G, 4% to
      Amoxicillin/clavulanic acid, 1% to Cefoperazone, 2% to Cefquinome, 35% to
      Neomycin, 22% to Gentamicin, 61% to Kanamy-cin and 11% to Lincomycin. 43% of the
      strains showed multiple resistance. 79% of the E. coli strains were sensitive to
      all the antibiotics tested. 20% exhibited resistance to Ampicillin, 9% to
      Neomycin and 10% to Kanamycin. A comparison of the own results with data of other
      authors in Switzerland shows no important changes in the resistance situation
      during the last 20 years. With the exception of two strains (Streptococcus spp.),
      all tested isolates were sensible against Cefquinome.

PMID- 14725184
TI  - [Influence of potassium on Mg- and Ca-metabolism in cows: effects and side
      effects of scientific research].
AB  - Results of scientific studies are obtained by analysing of the present knowledge
      of a current problem and a corresponding new experimental set-up. Under ideal
      conditions the data of the new study agree with the deduced working hypothesis.
      This general consideration is true for the well established correlation between K
      content and growth rates of plants. At low K concentrations (up to 3% of dry
      matter) K causes a linear increase of growth and finally a saturation. This
      positive effect of K on growth rates of plants is accompanied by some side
      effects. There is no doubt that a high intake of K is involved in the
      pathogenesis of grass tetany and of milk fever. The present publication gives
      some information about this correlation and discusses the discrepancy between the
      intention of a scientific study and possible "side effects", which cannot be
      predicted in many cases.

PMID- 14725185
TI  - [The use of avermectins in two goats with demodicosis].
AB  - This case report describes the treatment of demodicosis (Demodex caprae) in 2
      goats. The entire body surface of both goats was scattered with lens-large nodes
      from which pasty secretion emptied itself during palpation. One goat was
      administered 0.67 mg/kg Ivermectin orally once weekly for 12 weeks, the other
      goat was treated with 0.5 mg/kg Eprinomectin pour-on. The treatment led to an
      entire healing without any scar formation or depigmentations of the skin.

PMID- 14725186
TI  - [Frequency of diseases and death in hedgehogs].

PMID- 14725187
TI  - Lewis Thomas (1913-1993). The element of style.

PMID- 14725188
TI  - My romance with space.

PMID- 14725189
TI  - Malnutrition in Civil War armies.

PMID- 14725190
TI  - Re "Medical education and health care in Hong Kong".

PMID- 14725191
TI  - Eureka moments.

PMID- 14725192
TI  - Eureka moments.

PMID- 14725193
TI  - Eureka moments.

PMID- 14725194
TI  - Eureka moments.

PMID- 14725195
TI  - Eureka moments.

PMID- 14725196
TI  - Eureka moments.

PMID- 14725197
TI  - Eureka moments.

PMID- 14725198
TI  - Eureka moments.

PMID- 14725199
TI  - Eureka moments.

PMID- 14725200
TI  - Eureka moments.

PMID- 14725201
TI  - Eureka moments.

PMID- 14725202
TI  - Eureka moments.

PMID- 14725203
TI  - Eureka moments.

PMID- 14725204
TI  - [Blood substitutes--current evidence].
AB  - The aim to find an artificial substitute for human blood has failed in the past
      70 years and will most probably fail in the following future. Genomics,
      proteomics and posttranslational research have revealed that blood is our most
      complex and highly coordinated organ. Plasma substitutes can only promote a
      single function of plasma: the blood volume replacement. The even more complex
      coordination of the intraerythrocytic hemoglobin functions based on the
      allosteric structural changes induced by binding of O2, CO2 and NO can not be
      replaced safely by artificial oxygen carriers. Cell-free haemoglobin binds NO,
      which under physiological conditions coordinates O2 supply with the respiratory
      cycle and vasomotor function. The binding of NO to haemoglobin results in
      hypertonic crisis and in increase of leukocyte adherence and platelet
      aggregation. These complications may have a fatal outcome.

PMID- 14725206
TI  - [Fetal sex determination with real time PCR of fetal DNA in maternal plasma].
AB  - INTRODUCTION: Non-invasive methods using maternal plasma and serum for molecular
      genetic diagnosis become an important field of interest in prenatal genetic
      diagnosis. Free fetal DNA in maternal plasma and serum has been shown to be
      useful for fetal gender determination, and seems to offer a new possibility to
      perform non-invasive prenatal genetic diagnosis. A possible application is fetal
      sex determination for couples at risk of X-linked diseases. The aim of this study
      was to control the reliability and reproducibility of the real-time PCR
      amplification of the SRY region. MATERIALS AND METHODS: Maternal serum before
      amniocentesis, and amnionic fluid samples were obtained from 56 pregnant women
      during the 11th to 22nd weeks of gestation. Real-time PCR analysis of the SRY
      region was performed in order to determine the fetal sex. Routine karyotyping of
      cultured amnionic cells was also performed on the samples. Six cases were
      excluded. RESULTS: In 26 of 50 pregnancies were found male fetuses by cytogenetic
      analysis. Real time PCR of maternal plasma has been positive for the SRY region
      in 27 cases. In 47 cases the cytogenetic gender and the real-time PCR result was
      correlating. In one case of 46,XY karyotype the PCR reaction for SRY region was
      negative, in two cases of SRY positivity the karyotype was 46,XX. In this study
      are presented the results of fetal sex determination in maternal plasma using
      real time PCR method. CONCLUSIONS: The real time PCR detection of fetal DNA in
      maternal plasma seems to be an easy non-invasive method to determine the fetal
      sex at this gestational age. Our experience is promising in terms of the
      specificity and sensitivity of the method.

PMID- 14725205
TI  - [Secondary prevention of coronary disease--at the turn of the millennium in light
      of the Hungarian data of the EUROASPIRE I-II. Studies].
AB  - Relevant national societies attribute special importance to the secondary
      prevention of coronary patients. This is well formulated in their recommendations
      (9, 11). Actual clinical practice was studied in 1995-1996 by the EUROASPIRE I
      study. Its Hungarian data were published in 1999 (8). The scope of EUROASPIRE II
      in 1999-2000 was to study changes occurred in these 5 years. In this paper the
      authors intend to answer the question whether the clinical practice of secondary
      prevention of coronary patients showed any changes at the turn of the millennium.
      Participating centres, the criteria of patient selection and the applied methods
      were identical in the two studies. Hospital data of 516 patients below the age of
      70 were analysed. There was no difference between the two studies neither in the
      distribution according to gender and age, nor in the number of death.
      Documentation of the relevant data in the hospital records improved
      substantially: blood pressure was registered in every patient chart, lipid values
      in 91%. Information on smoking however is still missing in 1/3 of the patients,
      while on weight and height in half of them. The response rate at the follow up
      investigation on was 75%. The prevalence of obesity increased by 60%, that of
      smoking by 13% since the first investigation 5 years ago. This rate of increase
      is the largest among the 9 participating centres. The prevalence of hypertension
      decreased by 24.5% and the proportion of hypertensive patients receiving
      treatment increased by 7%. In spite of these blood pressure values over 140/90
      mmHg were found in 37% of the patients. The mean triglyceride value increased by
      53% and the prevalence of severe hypercholesterolaemia by 43%. Lipid lowering
      drugs are given to 51% of the patients in contrast to 22% 5 years earlier. In
      spite of this cholesterol values above 5.5 mmol/l were found in 42%. In respect
      of prophylactic drugs the proportion of patients receiving beta blockers
      increased from 58 to 84%. INTERPRETATION: The evaluation of complex risk of
      patients and their long-term care is still deficient. Drug treatment improved
      quantitatively but not qualitatively. This and the lack of lifestyle-improving
      medical efforts is reflected by the increase of the proportion of obese and
      smoking patients and the persistently high prevalence of hypercholesterolaemia
      and hypertension.

PMID- 14725207
TI  - [Combined therapy in pregnancy with primary antiphospholipid syndrome].
AB  - Patients with antiphospholipid syndrome have a high frequency of mid-pregnancy
      intrauterine growth retardation or fetal death. The authors report the case of a
      28 year old pregnant woman with antiphospholipid syndrome with severe obstetrical
      complications (spontaneous abortion, missed abortion) in the past history. By
      means of the administration of combined immunomudulant (intravenous
      immunoglobulin, steroid), anticoagulant and antiplatelet therapy we could prevent
      a subsequent pregnancy loss of the patient. Apropos of this case the authors give
      an overview on the monitoring of the disease and the therapeutical
      recommendations of the literature.

PMID- 14725208
TI  - [The Ljubljana classification of epithelial hyperplastic laryngeal lesions].
AB  - Epithelial hyperplastic laryngeal lesions caused by pathogenic factors injuring
      the mucosa may contain reactive and/or preneoplastic histological changes. The
      grading system devised and tested in Ljubljana comprises simple hyperplasia
      (benign spinous layer augmentation), abnormal hyperplasia (benign basal and
      parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and
      carcinoma in situ (actually malignant, but without invasion). In addition to
      making the diagnosis this classification is appropriate to evaluate the potential
      of any particular abnormality for progression into carcinoma. So it helps the
      clinician not only in planning the therapy and follow-up, but to assess the
      prognosis as well.

PMID- 14725209
TI  - [New possibilities in clinical use of angiotensin II receptor inhibitors].
AB  - The use of angiotensin-receptor blockers has already been outlined in cardiology
      and diabetology. In extending clinical indications of this drug class their
      pleiotropic actions might play a role: they are improving endothelial function,
      and their antiatherogenic effect is not related to antihypertensive action. It
      may also be important that while some antihypertensive agents are impairing
      sexual function, angiotensin-receptor blocking agents seem to improve sexual
      activity in hypertensive men. As there is alternative route for angiotensin II
      synthesis, there are patients in whom blockade of angiotensin II actions do need
      more aggressive treatment for proper therapeutic results. The discovery of
      angiotensin-receptor blocking agents made possible to produce this blockade in
      the tissues as well, and suggested combined administration of angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers for better
      clinical results. In patients with congestive heart failure data from an earlier
      pilot study (RESOLVD) suggested that combined use of these two drug classes would
      lead for a more complete blockade of the renin-angiotensin system with better
      clinical results, especially in those patients in the higher dose ranges. Recent
      results showed that using this drug combination cardiovascular mortality and
      hospitalization because of worsening heart failure could significantly be
      decreased (CHARM-Added study). More important data are expected from the ongoing
      ONTARGET program (Ongoing Telmisartan Alone and in combination with Ramipril
      Global Endpoint Trial).

PMID- 14725210
TI  - [Severe nephrotic syndrome in a young man taking anabolic steroid and creatine
      long term].
AB  - Anabolic steroids and creatine supplementation is one of the current abuse used
      by body builders. It is less known that this combination beside of many
      deleterious effects may also cause renal damage. Authors report a case of diffuse
      membranoproliferative glomerulonephritis type I in a 22-year-old man who had been
      taking continuously methandion in a large quantity and 200 grams of creatine
      daily, and was sent to the outpatient nephrologic unit with typical clinical
      signs of nephrosis syndrome. They also call attention to the role of the
      continuously consumed creatine in the renal failure.

PMID- 14725211
TI  - [Therapy of Hodgkin disease and non-Hodgkin lymphomas].

PMID- 14725212
TI  - [Contribution to the subject "Chronic pericarditis in Hodgkin disease"].

PMID- 14725213
TI  - [Cited and non-cited].

PMID- 14725214
TI  - Turning teamwork into quality care.
AB  - To promote quality in the healthcare setting, many organizations are realizing
      that they need to consider using teams to promote quality care. From establishing
      "a lean production system" to eliminating "waste"--in the form of poor customer
      service, employee dissatisfaction, and medical errors--to lowering average
      lengths of stays, two medical organizations found that taking a team approach can
      encourage good clinical care while improving bottom lines.

PMID- 14725215
TI  - [Laparoscopic surgery of the liver: state of the art].
AB  - Laparoscopic hepatic surgery has recently claimed its place among the minimally
      invasive techniques. Adequate technologies and experience both in laparoscopy and
      liver surgery are essential for its correct use. A review of the English
      literature on this subject is presented and the present state of the art
      discussed. Various topics are considered: staging, treatment of cystic lesions
      and treatment of benign and malignant primary and secondary tumours. Over the
      past five years various groups have published papers regarding case series,
      mainly concerning hepatic resection. More correct indications for the use of
      laparoscopy in liver surgery have been defined. In particular, laparoscopy is of
      great importance in the staging of primary and secondary liver cancer and in the
      treatment of cystic and benign lesions, mainly of the anterior segments. Less
      univocal are surgeons' attitudes towards the treatment of primary and secondary
      liver cancers. Laparoscopic liver surgery is gradually gaining wider and clearer
      acceptance in the treatment of hepatic lesions, while it has now virtually
      consolidated its role in the treatment of cystic lesions and in the staging of
      primary and secondary liver cancer.

PMID- 14725216
TI  - [Our experience with pharyngo-esophageal Zenker's diverticulum].
AB  - Zenker's diverticulum is the single most common diverticular event arising in the
      esophagus. Its physiopathology is universally recognized. Lack of coordination
      between the propulsive pharyngeal contractions and the release of the upper
      esophageal sphincter creates abnormally high pressure in the pharyngeal chamber,
      resulting in the collapse of the posterior wall of the hypopharynx, i.e., the
      Laimer-Killian triangle (or Killian's dehiscence). The mucosal hernia that
      develops constitutes the diverticulum, which grows in volume and above all in
      length and is compressed between two rigid structures, namely, the spine
      posteriorly and the trachea anteriorly. Swallowing progressively fills the
      diverticulum, which in turn leads to compression of the esophagus and hence to
      the characteristic symptom of "delayed dysphagia" or "dysphagia of the 3rd bite".
      These physiopathological considerations underpin the rationale for surgical
      treatment, namely upper esophageal sphincter myotomy and diverticulectomy, which
      is the standard approach used in the 44 cases presented here. A diverticulopexy
      was performed only once due to the patient's advanced age. Myotomy alone was
      performed in only one case, given the small size of the diverticulum. In two
      patients the standard procedure was carried out following emergency therapy for
      iatrogenic perforation of the diverticulum. The patient with cancer underwent
      chemo-radiotherapy after futile surgical attempts. Complications included
      transitory salivary leakage (1 case), and a transitory laryngeal nerve deficit (1
      case). Gastroesophageal reflux disease was present in two-thirds of the patients.
      A Nissen-Rossetti fundoplication was performed one year after treatment of the
      diverticulum in 5 patients. The following important aspects emerged: i) the
      incidence of neoplasia on the diverticulum; ii) the association and possible
      pathogenetic relationship with gastro-esophageal reflux disease iii) the validity
      of myotomy plus diverticulectomy as a treatment option in view of the negligible
      complications and the absence of relapse and/or persistence of dysphagia.

PMID- 14725217
TI  - Role of manometry and pH-metry in patients with symptoms and signs of
      gastroesophageal reflux disease.
AB  - To assess the correlation between esophageal manometry and 24-h pH-metry and the
      clinical, endoscopic and radiological picture, we carried out a retrospective
      analysis of the data of 175 patients in 2001-2002 with symptoms of
      gastroesophageal reflux disease and/or the established presence of esophagitis.
      The data were analyzed on the basis of the mean, standard deviation (SD) and
      percentage (%). Student's "t"-test was used to calculate statistical significance
      (P < 0.05). pH-metry was positive in 112 cases (64% R+) and negative in 63 (36% R
      ). Manometry revealed a significant sphincter hypotonia and a greater involvement
      of peristalsis in R+ patients. There was no significant relationship between
      symptoms and response to medical treatment compared to a positive pH-metry.
      Ninety-three (53%) patients presented esophagitis, while 58 (33%) had a hiatal
      hernia. Esophagitis was more frequent in R+ patients, while hiatal hernia was
      equivalent in both groups. In the diagnosis and treatment of gastroesophageal
      reflux disease, the first step is empirical medical therapy. If symptoms persist,
      esophagogastroduodenoscopy and barium radiology are performed to evaluate the
      presence of esophagitis and/or gastroesophageal reflux and any related diseases.
      Manometry and pH-metry (the gold standard for the diagnosis of gastroesophageal
      reflux disease) are therefore always performed in patients with atypical symptoms
      of patients to be subjected to surgical treatment.

PMID- 14725218
TI  - [Supra-esophageal manifestations of gastroesophageal reflux, a different
      diagnostic approach and an indication for laparoscopic Nissen fundoplication: our
      experience].
AB  - 24-hour oesophageal pH monitoring with a dual pH probe is considered to be the
      most sensitive test for diagnosing GORD-related otolaryngological manifestations.
      In this study we evaluate an initial diagnostic approach with digital
      videofluorography associated to the water siphon test and primary "ex juvantibus"
      therapy with proton pump inhibitors for patients with supra-oesophageal symptoms
      of GORD. The results of Nissen fundoplication surgical treatment are also
      assessed in some of these patients. Two hundred and thirty patients with
      suspected GORD-related supra-oesophageal symptoms were referred for
      videofluorography and the water siphon test. When hiatal hernia and/or reflux
      were found, patients were referred for medical therapy with proton pump
      inhibitors. Five patients, who had had a good or excellent response to the
      medical therapy, but had a recurrence underwent laparoscopic Nissen
      fundoplication and videofluorography 6 months after surgery. Within 6 months,
      more than 80% of patients had an excellent or good response to medical therapy.
      In patients undergoing laparoscopic Nissen fundoplication, hoarseness and chronic
      cough disappeared within 3 months and videofluorography showed good
      morphofunctional results of the surgery. In patients with GORD-related supra
      oesophageal manifestations, videofluorography plus the water siphon test is
      useful initial investigation, and laparoscopic Nissen fundoplication can be a
      valid alternative therapeutic option.

PMID- 14725219
TI  - [Liver transplantation in primary and secondary tumors of the liver. Review of
      the literature and perspectives].
AB  - Liver transplantation for malignancies still remains a controversial issue. There
      is concern for tumour recurrence, poor results and waste of organs, which in the
      sitting of organ shortage would penalize patients with non-malignant disease.
      Many centers worldwide perform liver transplantation (OLT) for hepatocellular
      (HCC) carcinoma associated with liver cirrhosis; the results in these cases are
      similar to those of patients transplanted for other indications. On the contrary
      are very few the centers that perform OLT for tumour other than HCC. This
      reflects that tumours other than HCC are less common and survival is poor
      compared to patients transplanted for non-malignant disease. Acceptable
      indications for OLT in case of tumours other than HCC are liver metastases from
      neuroendocrine tumours and epithelioid emangio-endothelioma. However should be
      kept in mind that OLT may offer the sole opportunity to cure the tumour and the
      underlying disease in some patients while providing meaningful palliation for
      others. At the present the overall experience with OLT for tumours other than HCC
      is still not significant and the results are discouraging. There is no evidence
      that OLT is beneficial for non-HCC tumours. Hopefully for the next future new
      adjuvant and neoadjuvant therapies combined with OLT would provide improved
      survival. Nevertheless, long-term survivors continue to be reported suggesting
      that OLT may be beneficial in individual selected cases with non-HCC tumour.

PMID- 14725220
TI  - [Laparoscopic surgery of the stomach: state of the art].
AB  - Over the past 10 years laparoscopy has been used for the staging of gastric
      cancer. It has also been used over the past decade for cancer resections, mainly
      stage I. In addition, it can be used for palliation in advanced stages. We have
      reviewed the main papers published in the English literature with a view to
      assessing the validity of laparoscopy in the staging of gastric cancer and in
      curative resections for cancer. Several studies published in the last 5 years
      have demonstrated the utility of laparoscopy in the staging of gastric cancer-
      mainly T3 and T4--and of cancer of the oesophagogastric junction. Laparoscopy can
      reduce the numbers of useless laparotomies performed and may be useful in
      selecting patients for neoadjuvant therapy. A number of studies have demonstrated
      the feasibility of laparoscopic gastric resections, mainly in stage I cancer. The
      advantages it affords consist above all in less postoperative pain and a quicker
      recovery. Laparoscopy, then, is useful in the staging of gastric cancer and in
      cancer of the oesophagogastric junction, mainly because it brings down the number
      of pointless laparotomies. More debatable is the issue of gastric resection for
      cancer, because of the low prevalence of early gastric cancer in Western
      countries.

PMID- 14725221
TI  - [Prognostic significance of chromosome and microsatellite instability in
      colorectal cancer].
AB  - The prediction of recurrence and the prognosis of colorectal cancer have always
      been related to the stage of the disease. Clinical pathological classifications
      are unable to predict the individual risk of recurrence and the prognosis which
      would also appear to be linked to additional factors, which have yet to be
      properly assessed, such as the genetic endowment of the tumour. In this study we
      assessed how microsatellite and chromosomal instability may help us to stratify
      two classes of risk of recurrence in patients at the same stage. From July 1996
      to June 1999 we prospectively collected data on 112 patients (59 male, 53 female)
      affected by colorectal cancer and undergoing surgery with a radical intent.
      Biopsies of normal and tumor tissue were submitted to DNA extraction and
      amplification to evaluate the presence of chromosomal instability (loss of
      heterozygosity) and microsatellite instability. Analysis of the data revealed
      that loss of heterozygosity in the long arm of chromosome 18 is associated, in
      patients with stage III colorectal cancer, with a higher risk of recurrence and
      therefore with a worse prognosis. Microsatellite instability proved to be
      associated with a better prognosis even in cases of recurrence.

PMID- 14725222
TI  - [Virtual surgical education: experience with medicine and surgery students].
AB  - The use of virtual reality simulation is currently being proposed within programs
      of postgraduate surgical education. The simple tasks that make up an operative
      procedure can be repeatedly performed until satisfactory execution is achieved,
      and the errors can be corrected by means of objective assessment. The aim of this
      study was to evaluate the applicability and the results of structured practice
      with the LapSim laparoscopic simulator used by undergraduate medical students. A
      significant reduction in operative time and errors was noted in several tasks
      (navigation, clipping, etc.). Although the transfer of technical skills to the
      operating room environment remains to be demonstrated, our research shows that
      this type of teaching is applicable to undergraduate medical students and in
      future may become a useful tool for selecting individuals for surgical residency
      programs.

PMID- 14725223
TI  - [Thyroid anaplastic tumor: our experience].
AB  - We report our experience over the past 10 years in the treatment of thyroid
      anaplastic carcinoma analysing retrospectively 21 cases of surgical treatment (7
      total thyroidectomies, 12 partial resection of the tumours and 2 biopsies). We
      consider the prognosis, which is invariably fatal, with no survival at 19 months
      and a mean survival of only 9 months, and assess the validity of a combined
      therapeutic approach (surgery + radiotherapy + chemotherapy) to increase survival
      and, above all, the patient's quality of life. The importance is stressed of
      through monitoring of risk factors consisting in concomitant or previous benign
      or malignant thyroid disease, considering total thyroidectomy to be necessary in
      principle for any variety of thyroid cancer. Lastly, we examine the survival
      trend in terms of residual disease and the presence or otherwise of remote
      metastases.

PMID- 14725225
TI  - [What is new in fasting guidelines of surgical patients? Review of the
      literature].
AB  - The concept of perioperative starvation requires an update on a more balanced
      physiological bias. The old British dictum "nil by mouth from midnight" is a
      thing of the past. We need to administer food and fluids as early as possible
      both before both before and after surgery and to avoid or reduce hospital
      infections. Resumption of bowel movements is very rapid, and the patients are fed
      and experience no thirst and thus have better compliance during their hospital
      stay. Moreover, the social cost is reduced. A short review of the rules of
      various Associations of Anaesthetists both in Europe and the US shows that today
      the starvation time is reduced, and re-feeding after surgery is implemented
      early. For clear fluids a 2-h period before surgery without ingestion of clear
      fluids is enough, whilst in most countries a 6-h period of starvation for solid
      foods is the rule, but if proper distinctions are made between the various
      nutrients given to the patients, this time could be reduced to 2-3 hours.

PMID- 14725224
TI  - [Classification and management of gynecologic acute abdomen at a secondary level
      hospital emergency department].
AB  - This study retrospectively evaluates the preoperative work-up and the
      classification and operative treatment of acute abdomen caused by gynaecological
      disorders in emergency admissions to our department. All female patients admitted
      in the emergency setting and operated on for gynaecological acute abdomen in our
      emergency department over the period from 1997 to 2002 were included in the
      study. A total of 103 patients were identified (54 undergoing emergency
      operations, 9 operated on within 72 hours, and 40 managed conservatively with
      medical therapy. The 54 emergency operations performed were 24 ovarian
      resections, 17 salpingectomies, 5 oophorectomies, 4 exploratory laparotomies, 2
      uterine polypectomies and 2 hysterectomies. The non-specific presentation of the
      disease and an inadequate preoperative work-up in these patients often led to a
      generic diagnosis at admission. This approach tends to increase the number of
      operations performed on an emergency basis, whereas a wait-and-see type of
      management should be adopted. A proper use of surgery is mandatory especially in
      those patients in whom preservation of reproductive capability has a major impact
      on outcome.

PMID- 14725226
TI  - Parotid gland tumours. Our experience and a review of the literature.
AB  - In this study the authors examine the experience of their department in treating
      parotid tumours, evaluating in particular the various surgical techniques as a
      function of the prognosis and the incidence of relapses. Between 1 January 1970
      and 31 December 2002, 336 patients with parotid tumour were observed in the
      Department of Surgical Sciences of "La Sapienza" University in Rome. Two hundred
      and thirty-nine patients with benign tumours and 65 with malignant tumours were
      analysed. As far as histological forms were concerned, the benign forms presented
      a prevalence of pleomorphic adenomas (55.2%) and of Warthin's tumours (36.4%). In
      the case of malignant tumours, the highest incidence was found for mucoepidermoid
      carcinomas (29.3%). In the case of benign neoplasms, the surgical strategy opted
      for was preneural parotidectomy performed in 148 cases (61.9%). Relapsing
      pleomorphic adenomas were observed in 11.65% of patients controlled, and
      relapsing Warthin's tumours in 8.7%. In malignant tumours, total parotidectomy
      was performed in principle, with possible enlargement modulated as a function of
      tumour stage; owing to causes related to the neoplasm, 18 patients (38.3%) died.
      In the treatment of benign parotid tumours, preneural parotidectomy is the
      preferred surgical strategy as it significantly reduces the relapse rate and,
      when performed by skilled surgeons, is characterized by a complication rate
      comparable to that of conservative surgery. In the treatment of malignant
      tumours, total parotidectomy is the basic procedure; extension of the action and
      the use of ancillary techniques are dependent on tumour stage.

PMID- 14725227
TI  - [Polypoid lesions of the gallbladder: indications for surgical treatment].
AB  - Through the study of a population of 176 patients with polypoid lesions of the
      gallbladder, our aim was to demonstrate the advantages of ultrasonography in the
      identification of those cases in which surgical intervention is indicated. From
      among our patients, specific criteria were used to select 92 patients to submit
      to cholecystectomy. These criteria were based on a thorough evaluation of the
      clinical data (patient's age, familiarity, presence of symptoms), and on careful
      examination of the ultrasonographic images (number and size of lesions, presence
      of associated cholelithiasis, state of the gallbladder wall). The histological
      results and the literature data confirmed the validity of our protocol. The risk
      factors for carcinoma are age (> 60 years), coexistence of gallstone disease, and
      the size of the lesions (> 10 mm). Therefore, when these risk factors are
      present, cholecystectomy is justified even in asymptomatic patients.

PMID- 14725228
TI  - [Complicated diverticular disease of the right colon. Diagnostic and therapeutic
      difficulties: our experience].
AB  - Right colon diverticulitis is an uncommon disease in Western countries. Often the
      disease is congenital and the clinical manifestations presenting at onset
      simulate the signs and symptoms typical of other diseases, such as acute
      appendicitis, appendicular abscess or caecal carcinoma. Since the diagnosis is
      usually intraoperative, diverticulectomy is recommended only in particular cases,
      with no complications resulting from inflammatory reactions. In the other cases,
      right hemicolectomy or segmental resection are the elective surgical treatments,
      depending on the patient's clinical condition and on the local anatomical
      situation. The authors describe 8 cases of complicated right colon
      diverticulitis, one of which with haemorrhagic complications, observed over the
      period from January 1999 to March 2003. The rareness and diagnostic and
      therapeutic difficulties of this disease are emphasised.

PMID- 14725229
TI  - [Usefulness of lateral internal sphincterotomy combined with hemorrhoidectomy by
      the Milligan-Morgan's technique: results of a prospective randomized trial].
AB  - Pain is invariably experienced after haemorrhoidectomy. Internal anal spasm is
      considered to be a major factor in the genesis of such pain. This prospective
      randomized study was designed to compare the effectiveness of two manoeuvres
      (surgical sphincterotomy and chemical sphincterotomy) in reducing post
      haemorrhoidectomy pain. Sixty patients (38 males, 22 females) with grade III and
      IV haemorrhoids were included in this study. In all cases resting anal pressure
      was reported in the range of 50-100 mm Hg. Group A patients underwent Milligan
      Morgan haemorrhoidectomy plus chemical sphincterotomy; group B patients underwent
      Milligan-Morgan haemorrhoidectomy plus internal left lateral sphincterotomy (0.8
      1 cm in length) and group C patients underwent Milligan-Morgan haemorrhoidectomy
      alone. The postoperative course was carefully evaluated and was found to be
      better in group B. None of the patients treated by surgical sphincterotomy
      developed incontinence. Two patients in group C developed anal strictures. When
      indicated, internal left lateral sphincterotomy (0.8-1 cm) is a safe procedure
      and reduces post-haemorrhoidectomy pain and stenosis.

PMID- 14725230
TI  - [Postoperative pain as complication of hernia surgical repair with mesh and
      plug].
AB  - The authors assess the incidence of locoregional chronic pain after inguinal
      hernia repair. One hundred consecutive patients, with a mean age of 65.4 years,
      suffering from primary monolateral inguinal hernia, underwent suture-less mesh
      plug hernioplasty. In all cases the inguinal nerves were identified. In the early
      postoperative period, a questionnaire was given to all patients in order to
      assess the frequency, type and intensity of postoperative locoregional pain and
      the impact of the pain on their quality of life. Sixty patients were available
      for follow-up with clinical examination and these were given the same
      questionnaire 2-4 years after hernioplasty. Pain intensity was scored by means of
      a visual-analogue scale (from 0 to 10). The incidence of locoregional pain after
      hernioplasty was 13.0% in the early postoperative period and 25.0% after a longer
      period of follow-up. None of the patients presented recurrent hernia. The
      symptomatic patients reported mild or moderate neurogenic pain. Severe pain was
      not reported. On the whole, the presence of mild-to-moderate chronic pain had no
      impact on the patients' quality of life. Our study confirms the high incidence of
      locoregional chronic pain even after sutureless mesh-plug hernioplasty, but that
      this has no serious effects on the patients' quality of life.

PMID- 14725232
TI  - Laparoscopic stoma creation.
AB  - Laparoscopic creation of an intestinal stoma may be preferable to an open
      operation. We report here our experience with faecal diversions. From April 1992
      to April 2003 we performed 55 procedures (23 end colostomies for Miles
      operations; 21 end colostomies for Hartman procedures; 9 loop colostomies and 3
      loop ileostomies). In 45 cases the procedure was completed laparoscopically. Ten
      (18%) of the cases required conversion due to bulky tumours (6 pts), obesity (2
      pts) and adhesions (2 pts). The indications for diversions were rectovaginal
      fistula (1 pt), anastomosis leakage (1 pt), unresectable rectal cancer (21),
      rectal cancer resectable by Miles operation (20 pts). The two ileostomies were
      constructed to protect colo-anal anastomoses. The average duration of surgery was
      50 minutes (range: 20-100) and 200 minutes in the case of Miles operations. The
      average postoperative hospital stay was 3 days (range: 2-5) and 7 days (range: 6
      9) after a Miles operation. The demand for analgesics was far lower than with
      traditional surgery and did not continue after postoperative day two. We had no
      intraoperative complications. There was no mortality. During the follow-up period
      all the stomas have functioned well but a prolapse occurred in one case (2.6%).
      The laparoscopic creation of intestinal stomas is safe, feasible and effective
      and can be performed with a low morbidity rate. Stoma construction is the
      simplest of all laparoscopic procedures because it requires little dissection and
      only minimal mesenteric handling. The length of the procedure is longer in
      patients who have had prior surgery, but prior surgery is not a contraindication
      and a laparotomy can be avoided in the majority of patients. Patients who are
      obstructed or have significant bowel dilation are less prone to damage with
      laparoscopic procedures. In addition to the benefits of laparoscopic techniques
      for the patients, a laparoscopic colostomy may be ideal for the surgeon as a
      basic, initial step in the performance of laparoscopic colorectal procedures.

PMID- 14725231
TI  - [Varicose vein recurrence after surgery of the sapheno-femoral junction: color
      Doppler ultrasonography study].
AB  - The aim of this study was to evaluate the accuracy and sensitivity of colour
      Doppler ultrasonography for the diagnosis of postoperative recurrent varicose
      veins in patients submitted to surgical ligation of the saphenofemoral junction
      with a view to classifying the recurrences according to the causes. We studied
      401 lower limbs in the orthostatic position with colour Doppler ultrasonography
      in 318 patients (64 M and 254 F) presenting postoperative varicose vein
      recurrence during the follow-up (12-60 months). We evaluated the type of reflux
      at the inguinal level under the Valsalva manoeuvre and divided them into 5 types.
      We observed an incomplete crossectomy (type 1) in 23.2% of the cases; an
      incontinent saphenofemoral junction, intact and in an anatomical site in 12.5%
      (type 2); a major tributary (double saphena) originating from the common femoral
      vein near to the crossectomy site in 10.2% (type 3); neovascularization in 9.7%
      (type 4) and the presence of a number of major tributaries from the veins of the
      perineal and pudendal region or from the abdominal parietal veins in 44.4% (type
      5). In all cases it was possible to note and classify the type of recurrence.
      Colour Doppler ultrasonography is an accurate, reliable tool for the diagnosis
      and classification of postoperative varicose vein recurrences in patients
      submitted to surgical obliteration of the saphenofemoral junction. It is decisive
      in the preoperative evaluation and follow-up of patients. In our experience, more
      than one half of the cases of recurrence were not due to an error of surgical
      technique.

PMID- 14725233
TI  - Synchronous colorectal and renal carcinomas. Is it a definite clinical entity?
AB  - The aim of the study was to assess the frequency of synchronous colorectal and
      renal cancers among our patients. To this end we reviewed 781 consecutive
      patients operated on for colorectal carcinoma in our institution. Three patients
      (0.4%) had diagnosis of synchronous renal-cell cancer during the work-up for
      their colorectal primary tumours. The colon and rectum are frequently affected by
      multiple malignant tumours. Second primaries are not frequently associated with
      colorectal cancer. On the other hand, renal cell carcinoma has been described as
      being associated with other synchronous malignancies in up to 27.4% of cases. A
      recent report has described a 4.8% incidence of synchronous colorectal and renal
      carcinomas, which is much higher than that previously reported in the literature
      (0.03-0.5%). We found a 0.4% incidence of simultaneous colorectal cancer and
      renal cell carcinoma. The latter was invariably asymptomatic and diagnosed during
      the work-up for the colorectal cancer. We are unable to confirm the observation
      of a higher than expected incidence of synchronous colorectal and renal
      neoplasms. Nevertheless, the surgeon should be conscious of this association,
      when considering renal lesions detected during the work-up for colorectal cancer.

PMID- 14725234
TI  - [Cystadenoma of the pancreas: 4 cases in our clinical experience].
AB  - Cystic neoplasms account for about 10% of all cystic lesions of the pancreas and
      less than 1% of all exocrine pancreatic neoplasms. The authors report 4 cases of
      pancreatic cystadenoma (3 women and 1 man; mean age 59 years; range: 41-72), 2
      serous and 2 mucinous, treated over the period from 1999 to 2002. The main
      symptoms were hypochondrial pain in two patients and diffuse abdominal pain in
      one while the fourth patient was asymptomatic. The patients were studied
      clinically by CT, echotomography and angiography. In three cases the tumours were
      located in the pancreatic body-tail, and in one case in the head. Serum amylase,
      lipase and tumour markers were all in the normal range. Only in one case was
      there an accurate preoperative diagnosis of tumour; in the other cases, a
      histological diagnosis was possible after surgical resection. Surgical treatment
      depended on tumour localisation: duodeno-cephalopancreatectomy for tumours in the
      head and distal pancreatectomy with splenectomy for tumours located in the body
      tail, Lymphadenectomy at levels I and II was performed in all cases. There was no
      postoperative mortality and only one female patient developed postoperative acute
      pancreatitis. During the follow-up CT scans showed no recurrence of the
      pancreatic tumours. In agreement with the international literature, we hold that
      all cystic tumours of the pancreas should be treated by surgical therapy, above
      all because of the major differential diagnosis problems they continue to
      present. Conservative treatment is justified only for well documented
      asymptomatic serous cystadenomas.

PMID- 14725235
TI  - [Granular cell tumors of the colon. Clinical case and review of the literature].
AB  - Abrikossoff's tumours are better known as granular cell tumours because of the
      typical microscopic aspect of their cytoplasm. They are uncommon neoplasms,
      probably of neurogenic origin, typically subepithelial and often benign. Rarely,
      they may be localised in the digestive tract, where they are mostly asymptomatic
      and tend to be discovered incidentally during endoscopic examinations indicated
      for other diseases. Histological examination with immunohistochemical staining
      usually yields the definitive diagnosis. Most authors agree as to the indication
      for endoscopic resection because of the possible, though rare, aggressive
      biological behaviour of these tumours. In the present paper we report on a case
      of granular cell tumour of the caecum, endoscopically resected and staining
      positively at the immunohistochemical search for the S100 protein.

PMID- 14725236
TI  - Pleural effusion as a complication of intrathoracic goitre.
AB  - The authors report their experience with a case of bilateral pleural effusions as
      a complication of intrathoracic goitre. They then go on to examine all the
      possible causes of this phenomenon. After discussing the anatomy of the superior
      mediastinum, they conclude that hydrothorax related to intrathoracic goitre could
      be the result of pressure of the mass on venous structures, especially on the
      superior vena cava, or on the intramediastinal lymphatic vessles, or, as in the
      case reported, on both.

PMID- 14725237
TI  - [Benign gastrojejunocolic fistula as a complication of gastric resection for
      adenocarcinoma].
AB  - Delayed gastrojejunocolic fistulas in patients previously operated for gastric
      cancer are often caused by local recurrence of the tumour. We present two cases
      of delayed gastrojejunocolic fistula without neoplastic recurrence. Both patients
      had been operated for adenocarcinoma several months earlier; a gastric Billroth 2
      resection was performed in both cases. The first patient arrived at our hospital
      for chest pain, dyspepsia, weight loss, vomiting and diarrhoea. Blood tests
      showed low levels of vitamin B, proteins and cholesterol. The second patient was
      admitted for lipothymia, hyporexia, proctorrhagia, diarrhoea and weight loss.
      Blood tests showed macrocytic anaemia and hypoproteinaemia. The radiological and
      endoscopic examinations revealed a gastrojejunocolic fistula in both cases. Since
      gastrojejunocolic fistulas are rarely resolved by conservative treatment, we
      performed a gastric resection with a histological examination to exclude tumour
      recurrence in both patients. The aetiopathogenesis of gastrojejunocolic fistulas
      is unknown. It is conceivable that some agents (such as bile) may damage a mucosa
      that has been weakened by nutritional deficiency and/or postsurgical
      microvascular damage. Early and delayed gastrojejunocolic fistulas present the
      same clinical manifestations, namely, diarrhoea, abdominal pain, weight loss and
      hypoproteinaemia.

PMID- 14725238
TI  - Spontaneous splenic haematoma in a teenager with infectious mononucleosis.
AB  - Spontaneous subcapsular splenic hematoma formation without rupture in infectious
      mononucleosis is a very unusual occurrence. Splenic rupture in infectious
      mononucleosis (Pfeiffer disease, or glandular fever) is a rare but life
      threatening complication. A conservative management is successful in those
      patients in stable condition. We describe the presentation and the clinical
      progress of a case in whom a sudden enlargement in hematoma's diameter needed a
      splenectomy to avoid the risk of blood effusion in the abdominal cavity. The
      contribution of the sonographic examination and follow-up in the diagnosis of
      infectious mononucleosis is emphasised.

PMID- 14725239
TI  - HIV/AIDS discrimination in the Asia Pacific region.

PMID- 14725240
TI  - Police abuses hinder HIV prevention in Cambodia and India.

PMID- 14725241
TI  - HIV testing: progress in Hungary, problems in Russia.
AB  - Voluntary anonymous HIV testing is about to become the norm in Hungary. Mandatory
      HIV testing, however, is widespread in Russia, contrary to the federal law on HIV
      prevention.

PMID- 14725242
TI  - El Salvador: legislature removes law allowing pre-employment HIV testing.

PMID- 14725243
TI  - South Africa: highest court orders government to provide antiretrovirals to
      prevent mother-to-child transmission.
AB  - On 5 July 2002, South African treatment activists won a significant victory when
      the Constitutional Court ordered the South African government to make the
      antiretroviral drug nevirapine available in public hospitals and clinics for the
      purposes of preventing mother-to-child transmission of HIV. The Court also ruled
      the government has a constitutional obligation to implement a program to realize
      the right of pregnant women and their newborn children to access health services
      to prevent transmission.

PMID- 14725244
TI  - Update to international guidelines on HIV/AIDS and human rights.
AB  - On 10 September 2002, the Office of the UN High Commissioner for Human Rights
      (OHCHR) and the Joint UN Programme on HIV/AIDS (UNAIDS) released a revised
      international guideline on "Access to prevention, treatment, care and support."
      The update to Guideline 6 of HIV/AIDS and Human Rights: International Guidelines
      reflects significant therapeutic, political, and legal developments in this area
      since the 12 guidelines were originally published in 1998. The new Guideline 6
      significantly expands the guidance given to governments on what international
      human rights norms require of them in relation to HIV/AIDS prevention, treatment,
      care and support.

PMID- 14725246
TI  - Olanzapine and women with borderline personality disorder.

PMID- 14725245
TI  - UN Commission on Human Rights adopts resolutions on access to medication, right
      to health.
AB  - In April 2002, the United Nations Commission on Human Rights adopted two
      resolutions that are important in the context of access to treatment. The
      Commission is the UN's leading body with respect to international human rights
      issues. It consists of 53 UN member states and meets annually. The Commission's
      resolutions can be found on the website of the Office of UN High Commissioner for
      Human Rights via www.unhchr.ch/ by clicking on "Documents of Charter-based
      bodies".

PMID- 14725247
TI  - Weighing the medical evidence. How can we lose weight? Protect our hearts?
      Control blood pressure? Docs are divided.

PMID- 14725248
TI  - Preferences, disparities, and the authenticity of patient choices.

PMID- 14725249
TI  - Characterizing preferences for health outcomes in economic evaluations.

PMID- 14725250
TI  - [Sick leave--causes, consequences, practice. A systematic literature review.
      Summary and conclusions by the SBU].

PMID- 14725251
TI  - [Effects of the water head-drop on performance of the self-forming bio-dynamic
      membrane].
AB  - To raise the water-head drop (WHD) is unbeneficial to the recovery of the self
      forming bio-dynamic membrane (SFDM). With the rising of the WHD, the stable flux
      of the SFDM gradually rised to the maximum, about 35 L.(m2.h)-1, but it had a
      trend to decline if the WHD was further raised. The duration of the stable stage
      of the SFDM declined remarkably with the WHD being increased in the recovery
      stage. The duration of the stable stage was more than 10 d when the WHD was 0.5
      cm in the recovery stage, but it was less than 5 h when the WHD was 10 cm. The
      causes of these phenomena were analyzed. It was proposed that each running cycle
      of the SFDM be started at the WHD of zero.

PMID- 14725252
TI  - Abstracts of the 24th Annual Meeting of the Society for Maternal-Fetal Medicine.
      February 2-7, 2004. New Orleans, Louisiana, USA.

PMID- 14725253
TI  - Carotid artery dynamics during head movements: a reason for concern with regard
      to carotid stenting?
AB  - PURPOSE: To evaluate carotid artery mobility patterns during head movements
      following carotid angioplasty/stenting (CAS). METHODS: In 7 patients (all men;
      mean age 69 years, range 65-76) who had undergone unilateral CAS, 3D time-of
      flight magnetic resonance angiography was performed, visualizing both carotid
      arteries in 5 different head positions (neutral, turned left and right, and bent
      forward and backward). Maximum intensity projection reconstructions were obtained
      to measure angulation at the proximal and distal stent junction. Configuration
      changes of the stented section of the carotid artery and the unstented
      contralateral artery were judged. Secondly, transverse sections at the level of
      the carotid bifurcation and at the skull base were used to calculate torsion
      shear in the common and internal carotid arteries (CCA, ICA) during left and
      right head position. Results were expressed as median (range). RESULTS: In
      neutral head position, maximal angulation at the distal stent junction was 34.3
      degrees (32.3 degrees-55.6 degrees). With the head bent forward, this angulation
      changed to 47.6 degrees (42.6 degrees-85.2 degrees, p=0.028) and when bent
      backward to 26.5 degrees (25.0 degrees-48.7 degrees, p=0.027). In all patients,
      configuration changes of the stented sections were absent. The contralateral
      unstented side showed diffuse configuration changes without specific angulation
      at one location. With the head turned left and right, the CCA on the stented side
      was subjected to 28.6 degrees (13.6 degrees-53.7 degrees) and 24.9 degrees (2.0
      degrees-50.6 degrees) of torsion shear, respectively. Torsion of the ICA was
      subsequently 18.1 degrees (12.7 degrees-40.5 degrees) and 15.2 degrees (2.9
      degrees-69.4 degrees). CONCLUSIONS: Following carotid stenting, sharp ICA
      angulation that are aggravated by forward bending of the head occur at the distal
      stent junction. The stented section of the carotid artery shows complete lack of
      flexibility despite highly flexible features of hte stents ex vivo. Both the CCA
      and ICA are subjected to considerable torsion shear with the head turned left and
      right. This shear is not accommodated by the current stent designs.

PMID- 14725254
TI  - Abstracts from the 25th International Epilepsy Congress. Lisbon, Portugal, 12-16
      October 2003.

PMID- 14725255
TI  - Advances in Marine Biology cumulative index volumes 20-44.

PMID- 14725256
TI  - [Abstracts of the 65th SIMLII National Congress. Skin and Occupation: Role of the
      Occupational Physician in the Prevention of Occupational Injuries from Biological
      Risks in the Workplace. 11-14 September 2002, Messina, Italy].

PMID- 14725257
TI  - Frequency of revaccination against smallpox.

PMID- 14725258
TI  - Asymptomatic severe acute respiratory syndrome-associated coronavirus infection.

PMID- 14725259
TI  - Hepatitis C antibodies among blood donors, Senegal, 2001.

PMID- 14725260
TI  - Prosthetic valve endocarditis due to Kytococcus schroeteri.

PMID- 14725261
TI  - When is a reservoir not a reservoir?

PMID- 14725262
TI  - Invasive Mycobacterium marinum infections.

PMID- 14725263
TI  - Rickettsialpox in Turkey.

PMID- 14725264
TI  - Human granulocytic ehrlichiosis in Estonia.

PMID- 14725265
TI  - Toxoplasma gondii and schizophrenia.
AB  - Recent epidemiologic studies indicate that infectious agents may contribute to
      some cases of schizophrenia. In animals, infections with Toxoplasma gondii can
      alter behavior and neurotransmitter function. In humans, acute infection with T.
      gondii can produce psychotic symptoms similar to those displayed by persons with
      schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in
      persons with schizophrenia and other severe psychiatric disorders and in controls
      have been reported; 18 reported a higher percentage of antibodies in the affected
      persons; in 11 studies the difference was statistically significant. Two other
      studies found that exposure to cats in childhood was a risk factor for the
      development of schizophrenia. Some medications used to treat schizophrenia
      inhibit the replication of T. gondii in cell culture. Establishing the role of T.
      gondii in the etiopathogenesis of schizophrenia might lead to new medications for
      its prevention and treatment.

PMID- 14725266
TI  - Cutaneous melioidosis and necrotizing fasciitis caused by Burkholderia
      pseudomallei.
AB  - In areas where melioidosis is endemic, stress on the healthcare system is
      substantial. Because clinical manifestations are protean, the illness is
      difficult to diagnose, and cutaneous Burkholderia pseudomallei infections can
      progress to necrotizing fasciitis. While it is and uncommon complication of
      cutaneous melioidosis, necrotizing fasciitis is potentially fatal and requires
      aggressive management, including early diagnosis, appropriate antibiotics
      selection and operative debridement.

PMID- 14725267
TI  - [Abstracts of the 12th annual meeting of the Ophthalmologists Society of Saxony
      Thuringia. 7-8 November 2003, Magdeburg].

PMID- 14725272
TI  - Abstracts of the 6th Asia Pacific Congress of Medical Virology. 7-10 December
      2003. Kuala Lumpur, Malaysia.

PMID- 14725274
TI  - Uniform requirements for manuscripts submitted to biomedical journals: writing
      and editing for biomedical publication.

PMID- 14725277
TI  - Reinforced prevention efforts for HIV.

PMID- 14725278
TI  - Drugs for HIV in South Africa.

PMID- 14725279
TI  - AIDS treatment for Kenyan workers.

PMID- 14725280
TI  - Abstracts from the 34th Annual Meeting of the American Association for Hand
      Surgery. Rancho Mirage, California, USA. January 14-17, 2004.

PMID- 14725283
TI  - Faculty of Medical Sciences 12th Annual Research Conference and Workshop on
      Ageing Well: A Life Course Perspective. November 12-14, 2003. Kingston, Jamaica.
      Abstracts.

PMID- 14725282
TI  - Abstracts of the UWI Medical Alumni Association 7th International Medical
      Conference. November 4-8, 2003, Bahamas.

PMID- 14725284
TI  - [Parkinson disease therapy: how great is the progress? Possibilities, limitations
      and future prospects?].

PMID- 14725285
TI  - Alexander the Great and West Nile virus encephalitis.
AB  - Alexander the Great died in Babylon in 323 BC. His death at age 32 followed a 2
      week febrile illness. Speculated causes of death have included poisoning;
      assassination, and a number of infectious diseases. One incident, mentioned by
      Plutarch but not considered by previous investigators, may shed light on the
      cause of Alexander's death. The incident, which occurred as he entered Babylon,
      involved a flock of ravens exhibiting unusual behavior and subsequently dying at
      his feet. The inexplicable behavior of ravens is reminiscent of avian illness and
      death weeks before the first human cases of West Nile virus infection were
      identified in the United States. We posit that Alexander may have died of West
      Nile virus encephalitis.

PMID- 14725286
TI  - [German Society of Psychiatry, Psychotherapy and Neurology 2003 Congress. Berlin,
      Germany, 19-22 November 2003. Abstracts].

PMID- 14725287
TI  - [Hans Erhard Bock. December 31, 1903 (interview)].

PMID- 14725290
TI  - To die for.

PMID- 14725294
TI  - Points to consider for aseptic processing.

PMID- 14725295
TI  - Abstracts of the 11th Annual EUPHA Meeting. Globalisation and Health in Europe:
      Harmonising Public Health Practices. Rome, Italy, 20-22 November 2003.

PMID- 14725296
TI  - Humboldt University beefs up technology transfer.

PMID- 14725297
TI  - Scripps lured to the Sunshine State.

PMID- 14725299
TI  - France critiques its incubator before refinancing.

PMID- 14725300
TI  - 21st-century emerging and reemerging infections.

PMID- 14725301
TI  - Proactive accounting: a key factor in the success of biotechnology startups.
AB  - Neglecting proper management of accounting functions can jeopardize the trust
      between a biotech company and it stakeholders.

PMID- 14725302
TI  - Abstracts of the 55th Annual Conference of the Cardiological Society of India.
      December 4-7, 2003, Kolkata, West Bengal.

PMID- 14725303
TI  - Tackling the Barriers to Participation and Performance. Abstracts of the 2003
      Australian Conference of Science and Medicine in Sport. 25-28 October 2003,
      Canberra, Australia.

PMID- 14725305
TI  - New strategies for the management of diabetes: insulin analogs and premixed
      insulin analogs.

PMID- 14725306
TI  - Influenza pandemic preparedness.

PMID- 14725307
TI  - Generalized vaccinia 2 days after smallpox revaccination.

PMID- 14725308
TI  - Salmonella enterica serovar Enteritidis, Japan.

PMID- 14725309
TI  - Tarnished adornment: The troubled history of Quebec's institut du radium.
AB  - In 1922 the Quebec government appropriated $100,000 for the purchase of radium to
      found an Institut du Radium at the University of Montreal. Opened largely through
      the initiative and drive of Dr. Joseph-Ernest Gendreau, the institut was the
      first organization devoted to radium therapy and cancer treatment in Canada. This
      paper describes the background, origins and development of the Institut with a
      focus on the medical, political, and cultural factors which led to its
      establishment. From the point of view of the Quebec government, the Institut was
      a way of showing its commitment to health care, of strengthening cultural bonds
      with France, and of demonstrating the province's emerging technological prowess.
      Radium was to be an adornment which showed off the scientific advancement of 20th
      century Quebec. Unfortunately, the Institut never achieved the scientific or
      cultural stature promised by the rhetoric. Which surrounded its opening, and this
      paper will examine the factors which led to its instability and eventual demise.
      In addition to an overwhelming clinical workload, chronic underfunding and
      geographic isolation, the Institut fell victim to medical politics. Its success
      was undermined by opposition from medical groups and competition from hospitals
      which led to the establishment of multiple radium centres in Montreal. A
      fundamental problem was confusion over whether its role should be a research
      institute, a general medical clinic, or a specialized cancer centre. Despite
      numerous financial and administrative crises and the severing of its academic
      affiliation in 1945, the Institut survived until 1967. Despite its troubled
      history, the Institut made an important contribution to Canadian medicine through
      its ground braking role in the establishment of radiotherapy and cancer
      treatment. In addition, the lessons learned from its difficulties proved useful
      to other provinces planning their own cancer programs.

PMID- 14725310
TI  - Factors influencing fluoroquinolone resistance.

PMID- 14725311
TI  - International travel and sexually transmitted disease.

PMID- 14725312
TI  - Salmonella in Denmark.

PMID- 14725313
TI  - Industry-related outbreak of human anthrax.

PMID- 14725314
TI  - In support of the pediatric health care home.

PMID- 14725315
TI  - A novel diastereoselective route to alpha-hydroxyalkyl dihydropyrans using a
      hetero Diels-Alder/allylboration sequence.

PMID- 14725316
TI  - Hospice: a historical perspective.

PMID- 14725317
TI  - What you should know about serving on community and association boards.

PMID- 14725318
TI  - Diversity your marketing.

PMID- 14725319
TI  - Status of medical mycology education.
AB  - The number of immunocompromised patients and subsequent invasive fungal
      infections continues to rise. However, the education of future medical
      mycologists to engage this growing problem is diminishing. While there are an
      increasing number of publications and grants awarded in mycology, the time and
      detail devoted to teaching medical mycology in United States medical schools are
      inadequate. Here we review the history in medical mycology education and the
      current educational opportunities. To accurately gauge contemporary teaching we
      also conducted a prospective survey of microbiology and immunology departmental
      chairpersons in United States medical schools to determine the amount and content
      of contemporary education in medical mycology.

PMID- 14725320
TI  - Phosphatase activity on the cell wall of Fonsecaea pedrosoi.
AB  - The activity of a phosphatase was characterized in intact mycelial forms of
      Fonsecaea pedrosoi, a pathogenic fungus that causes chromoblastomycosis. At pH
      5.5, this fungus hydrolyzed p-nitrophenylphosphate (p-NPP) to p-nitrophenol (p
      NP) at a rate of 12.78 +/- 0.53 nmol p-NP per h per mg hyphal dry weight. The
      values of Vmax and apparent Km for p-NPP hydrolyses were measured as 17.89 +/-
      0.92 nmol p-NP per h per mg hyphal dry weight and 1.57 +/- 0.26 mmol/l,
      respectively. This activity was inhibited at increased pH, a finding compatible
      with an acid phosphatase. The enzymatic activity was strongly inhibited by
      classical inhibitors of acid phosphatases such as sodium orthovanadate (Ki = 4.23
      micromol/l), sodium molybdate (Ki = 7.53 micromol/l) and sodium fluoride (Ki =
      126.78 micromol/l) in a dose-dependent manner. Levamizole (1 mmol/l) and sodium
      tartrate (10 mmol/l), had no effect on the enzyme activity. Cytochemical
      localization of the acid phosphatase showed electrondense cerium phosphate
      deposits on the cell wall, as visualized by transmission electron microscopy.
      Phosphatase activity in F. pedrosoi seems to be associated with parasitism, as
      sclerotic cells, which are the fungal forms mainly detected in
      chromoblastomycosis lesions, showed much higher activities than conidia and
      mycelia did. A strain of F. pedrosoi recently isolated from a human case of
      chromoblastomycosis also showed increased enzyme activity, suggesting that the
      expression of surface phosphatases may be stimulated by interaction with the
      host.

PMID- 14725321
TI  - Detection of Mala f and Mala s allergen sequences within the genus Malassezia.
AB  - Malassezia species are opportunistic yeasts that are involved in the pathogenesis
      of a number of skin diseases including atopic eczema/dermatitis syndrome.
      Previously, we cloned six allergens from Malassezia sympodialis isolate ATCC
      42132; these allergens are designated Mala s 1, and Mala s 5-Mala s 9. Three
      additional allergens, Mala f 2-Mala f 4, have been isolated from M. furfur by
      other investigators. The objective of the present study was to investigate the
      presence of these Mala sequences in seven Malassezia species. Genomic DNA
      amplification by PCR and sequencing showed that M. globosa, M. obtusa and M.
      sympodialis contain DNA sequences corresponding to all the allergens except Mala
      f 2 and Mala f 3. M. pachydermatis contains Mala s 1, Mala f 4, and Mala s 5-Mala
      s 8. M. restricta and M. slooffiae possessed Mala f 4 and Mala s 6. M. furfur was
      seen to possess Mala f 2-Mala f 4 as well as Mala s 5-Mala s 7. Our data from
      reverse-transcriptase PCR showed a more species-specific pattern of
      amplification. M. furfur evidenced expression of Mala f 2-Mala f 4. M. globosa
      and M. obtusa appeared to express only Mala s 6. M. pachydermatis expressed Mala
      f 4, Mala s 6, and Mala s 8, while M. restricta and M. slooffiae expressed Mala f
      4 and Mala s 6. M. sympodialis expressed all the allergens except Mala f 2 and
      Mala f 3. Different Malassezia species appear to contain both common and species
      specific allergen sequences.

PMID- 14725322
TI  - Epidemiology of Candida colonization in an intensive care unit of a teaching
      hospital in Kuwait.
AB  - The incidence of Candida infections in intensive care units (ICU) is increasing.
      Although most cases of candidemia are caused by commensal strains colonizing the
      patients' own body sites, recent studies have suggested that the source of
      Candida infection can also be exogenous. This study was carried out to
      prospectively investigate the frequency of Candida colonization among patients
      and health care personnel of an ICU of a teaching hospital in Kuwait. A total of
      57 patients and 45 nurses were investigated. Candida isolates were identified to
      the species level by the Vitek identification system. The typing of selected
      isolates was performed by randomly amplified polymorphic DNA (RAPD) using three
      different arbitrary primers (CARAPD1, AP3, CT5). Of the 526 samples collected
      from 57 patients, 180 (34%) yielded Candida species. These included 112 (62%) C.
      albicans, 37 (21%) C. glabrata, 15 (8%) C. parapsilosis, 11 (6%) C. tropicalis, 3
      (2%) C. krusei and 2 (1%) C. lusitaniae isolates. Thirty-seven patients (65%)
      were colonized by Candida at some point of stay in the ICU. Seven (12%) patients
      yielded more than one Candida species from the sites/specimens tested. The
      frequency of Candida isolation was highest from oropharynx, followed by rectum,
      groin, urine and trachea. Twenty-five (6%) of the 448 swabs from the nurses
      yielded Candida and included C. albicans (n = 16), C. parapsilosis (n = 4) and C.
      famata (n = 5). While all the three primers yielded varying patterns in RAPD
      analyses for each Candida species, the results obtained by AP3 were most
      discriminatory. The data showed that the colonizing Candida isolates recovered
      from various body sites of the patients, as well as the nursing staff, were
      different. However, when RAPD profiles of three blood culture isolates from
      candidemic patients were analyzed, the DNA fingerprint produced by one C.
      parapsilosis blood culture isolate was similar to C. parapsilosis recovered from
      the hands of two nurses, suggesting exogenous acquisition of infection.

PMID- 14725323
TI  - Humoral and cellular immune response to a Microsporum canis recombinant
      keratinolytic metalloprotease (r-MEP3) in experimentally infected guinea pigs.
AB  - In order to better understand the host-fungus relationship in Microsporum canis
      dermatophytosis and to identify major fungal antigens, the immune response to a
      crude exoantigen preparation and to a purified recombinant keratinolytic
      metalloprotease (r-MEP3) was evaluated in guinea pigs experimentally infected
      with M. canis. Humoral and cellular immune responses were assessed from day 0 to
      day 57 post-infection (PI), the former by enzyme-linked immunosorbent assay
      (ELISA) and the latter via a lymphocyte proliferation assay. Infected guinea pigs
      developed humoral and cellular responses to both M. canis exoantigen and r-MEP3,
      while no specific immune response to these antigens was observed in control
      animals. This is the first report on the development of both humoral and cell
      mediated immune responses to a purified keratinase in M. canis dermatophytosis.

PMID- 14725324
TI  - Interactions of human phagocytes with moulds Fusarium spp. and Verticillium
      nigrescens possessing different pathogenicity.
AB  - Fusarium spp. are emerging as important causes of invasive fungal infections.
      They tend to have decreased susceptibility to antifungal agents, making host
      defences very important. The ability of human phagocytes to cause damage to
      hyphae of Fusarium solani, F. oxysporum and Verticillium nigrescens, a mould with
      very low pathogenicity, was assessed using the 2,3-bis[2-methoxy-4-nitro-5
      sulphophenyl]2H-tetrazolium-5-carboxanilide (XTT) metabolic assay. The oxidative
      burst, evidenced as superoxide anion (O2-) production, of phagocytes in response
      to hyphae was also investigated, as well as phagocytosis of conidia by monocyte
      (MNC)-derived macrophages (MDM). Hyphal damage by polymorphonuclear leukocytes
      (PMNL) and MNC showed a linear trend increasing with effector cell:target cell
      (E:T) ratio. Although no significant differences were observed for PMNL, MNC
      induced damage to F. solani hyphae was lower than that seen with F. oxysporum
      hyphae at an E:T ratio of 20:1 and with V. nigrescens hyphae at ratios of 1:1,
      5:1 and 20:1 (P < 0.05). In contrast, levels of O2- production by phagocytes in
      response to F. oxysporum were lower than those induced in response to the other
      fungi (P < 0.01). The average number of V. nigrescens conidia ingested by MDM was
      higher than that of conidia of the other fungi (P < 0.01). Phagocytes respond to
      the test fungi differentially, with F. solani being the least susceptible to
      damage by MNC. This may correlate with the observation that, compared to the
      other fungi studied, it causes a relatively high incidence of infections in
      neutropenic patients.

PMID- 14725325
TI  - Haemolytic activities of Trichophyton species.
AB  - Dermatophytes are keratinophilic fungi able to invade the stratum corneum of the
      skin and other keratinized structures. The pathogenic interactions between host
      and fungus are poorly understood. Some enzymes, especially keratinases, have
      previously been taken into consideration as virulence factors. Haemolysins have
      not been evaluated in this regard, though they are known to play an important
      role in the host-parasite interaction in bacterial infections. We investigate the
      haemolytic activity of four Trichophyton species: T. rubrum, T. mentagrophytes
      complex, Tequinum and T. verrucosum. The strains were tested on Columbia agar
      with 5% blood from horses, cattle and sheep. They show different haemolytic
      activities. T. rubrum and T. equinum produce a zone of complete haemolysis
      followed by a small zone of incomplete haemolysis around the colony. T.
      mentagrophytes and T. verrucosum produce a zone of complete haemolysis.
      Haemolytic activity is pronounced in dermatophytes and may play an important role
      as a virulence factor.

PMID- 14725326
TI  - Ajoene and 5-fluorouracil in the topical treatment of Cladophialophora carrionii
      chromoblastomycosis in humans: a comparative open study.
AB  - Ajoene and 5-fluorouracil (5-FU) are compounds that have shown in-vitro activity
      against Cladophialophora carrionii, an important etiologic agent of
      chromoblastomycosis. An open comparative trial was conducted to assess safety and
      effectiveness of topical ajoene and 5-FU in the treatment of localized
      chromoblastomycosis. Thirty-seven patients with a clinically and mycologically
      confirmed diagnosis were randomly distributed into two groups allocated to ajoene
      (0.5% gel; n = 19) or 5-FU (1% cream; n = 18). Topical treatment was applied to
      localized lesions (< or = 2.5-cm diameter) once a day, with occlusion, for 12-16
      weeks. Complete clinical and mycological remission was achieved in 14/19 patients
      (74%) treated with ajoene and 14/18 patients (78%) treated with 5-FU. All 5-FU
      treated patients developed a post-treatment scar at the site of the lesion, while
      ajoene-treated patients showed only a slight depigmentation of the skin. The
      differences observed in cure rate between ajoene and 5-FU are not statistically
      significant. Follow-up of all patients for 4 years revealed no relapses in the
      ajoene-treated group, while one patient in the 5-FU-treated group had a relapse 6
      months after the end of therapy. This trial represents the first clinical use of
      ajoene in the control of a deep mycosis.

PMID- 14725327
TI  - Epidemiology, presentation, management and outcome of candidemia in a tertiary
      care teaching hospital in the United Arab Emirates, 1995-2001.
AB  - Sixty episodes of candidemia among hospitalized patients in the United Arab
      Emirates (0.77/1000 discharges) in 1995-2001 were identified through case
      retrieval. All patients had malignancy (65%) or serious non-malignant disease
      (35%). Candida albicans accounted for 45% of isolates. Non-C. albicans Candida
      species occurred more frequently than C. albicans in adults (67%), hematologic
      malignancy patients (58%), and cases of breakthrough candidemia (83%) and were
      prevalent overall in 2000-2001 (67-73%). C. tropicalis was identified in 15% of
      cases, C. glabrata in 5%, C. parapsilosis in 5%, C. inconspicua in 2%, C. famata
      in 2% and C. lusitaniae in 1%. Delayed diagnosis or treatment was common, as was
      Karnofsky scale < or = 40%, septic shock, and inadequate dosage or duration of
      antifungal drug therapy. Crude mortality was 50%, and mortality attributable to
      candidemia was 30%. Univariate analysis indicated patients were more likely to
      die (odds ratio for death [95% CI]) if they had been stationed in the intensive
      care unit (ICU) (4.76 [1.31-17.2]), had a Karnofsky scale < or = 40% (38.76 [4.66
      322.47]), or suffered septic shock (9.88 [2.9-33.65]). They were more likely to
      survive in cases with concomitant bacteremia (0.25 [0.07-0.91]), adequate
      antifungal dose (0.28 [0.08-0.94]), and removal of central lines (0.26 [0.07
      0.95]). The high association of bacteremia with candidemia (70% of cases) is
      unusual. The apparent survival benefit experienced by patients who had bacteremia
      (odds ratio for survival on multivariate analysis = 2.40 [0.28-20.17], P < 0.03)
      is novel.

PMID- 14725328
TI  - Fungal peritonitis caused by Bipolaris spicifera.
AB  - An episode of fungal peritonitis was produced by Bipolaris spicifera in a 3-year
      old girl with chronic renal failure secondary to uremic-hemolytic syndrome and
      who was under treatment with continuous ambulatory peritoneal dialysis (CAPD).
      Previously, an episode of purulent peritonitis caused by Pseudomonas spp. had
      been treated successfully with combined antibacterial therapy for 10 days.
      Microscopic and macroscopic examinations of the freshly collected purulent
      dialysate were negative for fungal structures and bacteria. The fungus grew from
      the dialysate plated on Sabouraud dextrose agar and was also macroscopically
      recognized as a colony attached to the inner wall of the Tenckhoff catheter.
      Specific cultures of dialysate for common bacteria and mycobacteria were
      negative. The patient was successfully treated with early catheter removal and
      empirical administration of 200 mg/day oral fluconazole for 2 weeks.
      Subsequently, a new catheter was placed and the patient continued well on CAPD.
      Post-treatment control cultures of dialysate for fungi, bacteria and mycobacteria
      were negative and the cell count returned to normal.

PMID- 14725329
TI  - Pneumocystis jirovecii dihydropteroate synthase genotypes in French patients with
      pneumocystosis: a 1998-2001 prospective study.
AB  - Dihydropteroate synthase gene (DHPS) mutations at codons 55 and 57 have been
      associated with sulfa/sulfone resistance in Pneumocystis jirovecii strains from
      patients who previously received prophylaxis. To evaluate the prevalence of these
      mutations, a portion of P. jirovecii DHPS gene was analysed using PCR combined
      with restriction fragment length polymorphism (RFLP) analysis in 92
      bronchoalveolar fluid samples collected between January 1998 and September 2001
      from French patients with pulmonary pneumocystosis (PCP). Seventy-six samples
      contained the wild-type DHPS genotype (82.6%) and 16 contained a mutant genotype
      (17.4%). Twelve out of the 16 isolates with a mutant DHPS genotype corresponded
      to patients who had never received sulfa or sulfone prophylaxis, suggesting that
      DHPS mutants may be acquired de novo. There was no significant difference in
      favourable or adverse outcome in PCP caused by the wild or mutant DHPS genotypes
      (P = 0.34).

PMID- 14725330
TI  - Simplified method for producing Paracoccidioides brasiliensis exoantigens for use
      in immunodiffusion tests.
AB  - A simplified method to produce Paracoccidioides brasiliensis exoantigens for
      immunodiffusion testing is proposed. It uses technology accessible for small
      laboratories with few resources in Latin America, where paracoccidioidomycosis is
      endemic. This procedure may replace the more complex procedure, originally
      proposed by Camargo et al. in 1988, that is currently commonly used. It is based
      on the production of exoantigen by P. brasiliensis isolate B339, a good secretor
      of the characteristic 43000-Da glycoprotein gp43.

PMID- 14725331
TI  - Use of Helicobacter pylori-specific antibodies in the evaluation of intestinal
      metaplasia and gastric dysplasia.
AB  - It is believed that Helicobacter pylori acts mainly during the initial phases of
      gastric carcinogenesis. Therefore, this study aims to assess the usefulness of H.
      pylori diagnosis in patients with chronic gastritis (CG), intestinal metaplasia
      (IM) and dysplasia--conditions that are associated with gastric cancer. A cross
      sectional study of 94 patients was performed, which involved endoscopic biopsy
      and determination of specific serum anti-H. pylori antibodies (IgA, IgG and IgM)
      by enzyme-linked immunosorbent assay (ELISA). Biopsies were taken from the
      gastric antrum and corpus, and from endoscopic lesions. Two specimens per patient
      were used for bacterial culture. H. pylori infection status, used as the gold
      standard, was based on culture results. Validity measures were determined and
      receiver operating curve (ROC) was used to determine the best cut-off for serum
      antibody levels. Histopathological evaluation (n = 160) was performed
      independently by two pathologists. Lesions consistent with CG were found in 86
      patients (91%), consistent with IM in 69 patients (73%) and with dysplasia in
      five patients (5%). In the 86 patients with CG, 38 (44%) were infected by H.
      pylori, as were 26 (38%) and one (20%) with IM and dysplasia, respectively
      (P=0.039). Area under the curve (AUC) was 0.40 (95% confidence interval [CI]:
      0.28-0.51) for IgM, 0.69 (0.58-0.80) for IgA and 0.83 (0.74-0.92) for IgG for the
      diagnosis of H. pylori infection. Best cut-off was 41 u/mL for IgG, with a
      sensitivity (95% CI) of 90% (84-96%) and a negative predictive value (NPV) of 91%
      (85-97%). For IgA the results were 22 u/mL, 74% (65-83%) and 77% (68-86%),
      respectively. Prevalence of H. pylori appeared to decrease with increasing
      severity of the gastric lesion. In conclusion, it is suggested that non-invasive
      serological evaluation of anti-H. pylori (IgG) status after eradication therapy
      for peptic ulcer disease could be extended, after proper assessment of cut-off
      values and their validation, to the follow-up of patients with CG and IM.

PMID- 14725332
TI  - Is subtyping of intestinal metaplasia in the upper gastrointestinal tract a
      worthwhile exercise? An evaluation of current mucin histochemical stains.
AB  - Intestinal metaplasia is a premalignant condition that occurs in the upper
      gastrointestinal tract and can be subdivided into three types (I, II and III).
      Previous studies suggest that type III carries the highest cancer risk. The high
      iron diamine/alcian blue (HID/AB) technique traditionally has been used to
      identify this subtype; however, the technique uses reagents that are toxic and
      potentially carcinogenic. Therefore, in this study we evaluate various
      alternative histochemical techniques. Our results indicated that the only
      suitable alternative is Gomori's aldehyde fuchsin/AB technique. The study also
      revealed that subtyping of intestinal metaplasia is a subjective procedure, open
      to varying interpretation. Consequently, we suggest that previous work linking
      cancer risk to metaplasia subtypes should be viewed with some circumspection.

PMID- 14725333
TI  - ABC chromogenic agar: a cost-effective alternative to standard enteric media for
      Salmonella spp. isolation from routine stool samples.
AB  - Salmonellosis is the second most common cause of bacterial gastroenteritis, yet
      the yield from routine stool culture is low. Commonly used selective enteric
      media have poor specificities for salmonella identification, resulting in a high
      laboratory workload. A special chromogenic medium, ABC agar, is a promising
      alternative but its cost-effectiveness has not been evaluated in diagnostic
      laboratories. A collaborative study is therefore undertaken in two district
      general hospitals laboratories. Routine stool samples (n=866) were subcultured
      onto ABC agar half plates after selective enrichment in selenite broth.
      Similarly, 246 and 620 stool samples were subcultured onto desoxycholate lactose
      sucrose (DCLS) and xylose lactose desoxycholate (XLD) whole agar plates,
      respectively. Salmonella spp. were isolated from only 14 (1.6%) of stool samples
      tested. Specificity was significantly higher for ABC (98%) than DCLS (67%) or XLD
      (78%) agars. Welcan workload units (ABC 4.8, XLD and DCLS both 7.3) and costs per
      specimen (ABC 1.26 pounds sterling, DCLS 3.81 pounds sterling and XLD 1.83 pounds
      sterling) were similarly lower with ABC agar. The results indicate that ABC
      chromogenic agar offers improvements in specificity, workload and costs over
      conventional enteric media for Salmonella spp. isolation.

PMID- 14725334
TI  - Effect of long-term irbesartan treatment on endothelium-dependent vasodilation in
      essential hypertensive patients.
AB  - Endothelial dysfunction plays a pivotal role in the development of essential
      hypertension and its complications. The purpose of this study is to assess the
      effect of antihypertensive treatment with the angiotensin receptor blocker
      irbesartan on endothelial function in a group of essential hypertensive patients.
      Thirty-two untreated hypertensives are examined at baseline and at the end of a
      six-month period of irbesartan treatment. Endothelium-dependent and -independent
      responses are determined by measuring changes in forearm blood flow (FBF) by
      strain gauge plethysmography in response to intrarterial infusions of
      acetylcholine (endothelium-dependent vasodilation [EDV]), sodium nitroprusside
      (endothelium-independent vasodilation [EIV]), with and without the addition of
      the nitric oxide (NO) synthase inhibitor L-NMMA. Plasma endothelin, plasma and
      urinary nitrates and nitrites, and cyclic GMP are measured at baseline and at the
      end of treatment. Irbesartan promoted a significant increase in EDV (from 433+/
      147% to 488+/-75%; P=0.027) and EIV (from 442+/-130% to 495+/-104%; P=0.041). L
      NMMA-induced vasoconstriction was significantly enhanced after irbesartan
      treatment (relative decrease of FBF from 33.4+/-9.5% to 39.5+/-5.6%; P=0.001).
      Plasma concentrations of endothelin fell significantly after irbesartan treatment
      (from 5.78+/-1.86 to 4.16+/-1.52 pg/mL; P=0.001). We concluded that long-term
      irbesartan treatment enhances both endothelium-dependent and -independent
      vascular vasodilation capacity. In addition to this non-specific effect,
      irbesartan restores the vasoconstriction capacity of NO synthase inhibitors,
      suggesting a direct effect on tonic NO release, and decreases endothelin
      production. These actions may play an important role in the vascular protecting
      effects of irbesartan.

PMID- 14725335
TI  - Guanosine deaminase in human serum and tissue extracts--a reappraisal of the
      products.
AB  - Of the human salvage enzymes that deaminate ribonucleosides, two--cytidine
      deaminase and adenosine deaminase--have been found particularly useful for
      diagnostic purposes. In humans, no enzymes are present that can directly
      deaminate the bases of these ribonucleosides. Indeed, the only enzyme present
      that can directly deaminate a base is guanine deaminase, and the diagnostic
      usefulness of this enzyme has been well documented. The aim of this study is to
      identify the origin of the ammonia formed when human sera and tissue extracts are
      incubated with buffered guanosine, and to clarify whether the ammonia comes from
      the deamination of guanosine by guanosine deaminase or is produced as a result of
      deamination of guanine formed as a breakdown product of guanosine by purine
      nucleoside phosphorylase (PNP). Apparent deamination of guanosine by guanosine
      deaminase in human sera and tissue extracts was found to be due to two enzymes
      acting in tandem when the products of the reaction were examined by HPLC. The
      ribose was first removed from guanosine by PNP to form guanine, which was then
      deaminated to xanthine by guanine deaminase.

PMID- 14725336
TI  - Irish strains of Neisseria meningitidis: characterisation using multilocus
      sequence typing.
AB  - A total of 56 Neisseria meningitidis strains are analysed using multilocus
      sequence typing (MLST). Twenty-nine distinct sequence types (STs) were
      identified, eight of which were new. Four known hypervirulent clones--ST-11
      (electrophoretic type [ET]-37) complex, ST-44 complex (lineage 3), ST-32 (ET-5)
      complex and ST-8 complex (cluster A4)--were identified by MLST in 35 disease
      associated and four carrier strains. Two other clones (ST-22 complex and ST-269
      complex) were identified in nine disease-associated and one carrier strain. The
      remaining strains were heterogeneous. Additional sequencing within the FumC gene
      further distinguished the ET-15 clone within the ST-11 (ET-37) clonal complex.
      This resolution of isolates into genetic clones by MLST enhances the more
      traditional techniques of serotyping and serosubtyping. The data obtained
      established that hyperendemic meningococcal disease in Ireland could be
      attributed to strains belonging to four major hypervirulent clones, all of which
      account for elevated levels of disease worldwide. The extra information provided
      by MLST will be used to study the population structure and epidemiology of N.
      meningitidis and will allow a comparison of Irish strains with those circulating
      globally.

PMID- 14725337
TI  - Antigenaemia and antibody response to Leishmania donovani stage-specific antigens
      and rk39 antigen in human immunodeficiency virus-infected patients.
AB  - In order to define the possible markers for the early diagnosis of asymptomatic
      visceral leishmaniasis in human immunodeficiency virus (HIV)-infected
      individuals, the antigenaemia and antibody response to stage-specific Leishmania
      donovani and rk39 antigens is assessed by enzyme-linked immunosorbent assay
      (ELISA) and immunoreactivity to stage-specific antigens analysed by Western blot.
      Serum samples from two out of 100 HIV-infected individuals were found positive
      for antigenaemia, antibody response to stage-specific L. donovani antigens and
      rk39 antigen, and one sample was also positive for antigenaemia and antibody
      response to L. donovani antigens, while antibody detection to rk39 antigen was
      not carried on this sample. Additionally, one sample was found positive for
      amastigote antigenaemia and antibody response to amastigote antigen, while in
      this patient promastigote antigenaemia and antibody response to promastigote L.
      donovani and rk39 antigen could not be detected. One sample was found positive
      for antigenaemia, antibody response to amastigote antigen and negative for
      antibody response to promastigote antigen, while in this patient response to rk39
      antigen was borderline. Although antibody response to rk39 antigen could be
      detected in 9/88 (10%) HIV-infected individuals, in six of these nine patients
      neither antigenaemia nor antibody response to stage-specific L. donovani antigens
      could be detected. All 10 confirmed visceral leishmaniasis and HIV-negative
      control patients had positive antigenaemia and antibody response to L. donovani
      amastigote and promastigote antigens, while all the normal healthy individuals
      were negative. The study indicated that detection of antibody response to rk39
      antigen, amastigote antigenaemia and antibody response to amastigote antigen may
      prove to be better markers than detection of promastigote antigenaemia, antibody
      response to promastigote antigen and immunoblot reactivity.

PMID- 14725338
TI  - Toxoplasma gondii from liquid nitrogen for continuous cell culture: methods to
      maximise efficient retrieval.
AB  - This study aims to increase the efficiency of continuous growth of Toxoplasma
      gondii in HeLa cells from tachyzoite stocks frozen in liquid nitrogen. Freezing
      and retrieval of tachyzoites for continuous cell culture requires more stringent
      protocols than those published for animal culture. The freezing and retrieval
      conditions are optimised so that a quality harvest (> or = 1 x 10(6)
      tachyzoites/mL, > or = 90% viability) can be produced using T. gondii recovered
      from liquid nitrogen as fast and reliably as possible. Retrieval success rate
      increased from 36% to 100%. An improved freezing procedure using chilled reagents
      and freshly harvested parasites, and adoption of an effective recovery protocol
      with retrieval of 3 x 10(7) tachyzoites into 75 cm2 flasks, change of maintenance
      media after six hours and subsequent blind passage all contributed to this
      success. The result is faster and more dependable production of T. gondii for
      diagnostic and experimental use.

PMID- 14725339
TI  - Prevalence of HLA-B27 among donors and recipients for renal and bone marrow
      transplantation in Mauritius.
AB  - In this study, the frequency of the tissue antigen HLA-B27 is studied in 494
      donors and recipients for renal and bone marrow transplantation on the multi
      ethnic island of Mauritius, the majority of the population of which is of Indian
      descent. Although results showed a prevalence rate of 4.3%, inter-racial
      variation was not observed between the major ethnic groups (P>0.05). These
      findings are comparable with the results of studies on HLA-B27 prevalence rate in
      India, and lend support to the argument that the HLA-B27 test should not be used
      on a routine basis to diagnose HLA-B27-related rheumatic disorders in Mauritius.

PMID- 14725340
TI  - HLA-B27 allele diversity in Indians: impact of ethnic origin and the caste
      system.
AB  - HLA-B27 is a serological specificity which encompasses an increasing number of
      subtypes that show varied racial/ethnic prevalence in the world. Here, data from
      5129 Indians (4500 population and caste; 629 tribal) is compiled from the
      literature. In addition, HLA-B27 subtyping of 58 positive individuals from
      Maharastra is presented. Analysis revealed an increased B27 antigen frequency
      among the north Indian groups (>5%) compared to the south Indian groups (<5%).
      HLA-B27 subtyping identified B*2704 (34.48%), B*2705 (36.2%), B*2707 (15.51%),
      B*2708 (10.34%) and B*2714 (3.44%) alleles in the population groups from
      Maharastra, but these differed in their distribution among the caste and tribal
      groups studied. The study showed that more extensive subtyping in other Indian
      caste groups will be necessary to resolve the evolutionary implications of HLA
      B27 subtypes and their relationship to disease association in the Indian context.

PMID- 14725341
TI  - Pathogen inactivation of platelet concentrates and fresh frozen plasma.
AB  - Transfusion of blood products carries the risk of pathogen transmission, despite
      careful donor selection and screening tests. This is due to viral transmission
      from window-period donations, the emergence of new pathogens such as variant
      Creutzfeldt-Jakob disease, for which routine screening tests are not yet
      available, and to bacterial contamination. Techniques have been developed to
      inactivate pathogens in both fresh frozen plasma and platelet concentrates. The
      relative benefits to the recipient, and the ease of incorporation into blood
      component processing are considered for the technologies currently available.

PMID- 14725342
TI  - Low incidence of Neisseria meningitidis serogroups B and C in lower respiratory
      tract secretions in patients with cystic fibrosis.

PMID- 14725343
TI  - Omics research and bioinformatics--joined-up thinking or anarchy?

PMID- 14725344
TI  - In silico tools for signal transduction research.
AB  - Signal transduction is a fundamental process that takes place in all living
      organisms and understanding how this event occurs at the cellular level is of
      vital importance to virtually all fields of biomedicine. There are several major
      steps involved in deciphering the signalling pathways: (a) Which molecules are
      involved in signalling? (b) Who talks to whom?, ie making sense of the molecular
      interactions in a context-dependent way. (c) Where are the signalling events
      taking place?, eg when a resting cell becomes activated. The challenge lies in
      reconstructing signalling modules and networks evoked in a particular response to
      a single input as well as correlating the signalling response to different
      cellular inputs. There is also the need for interpretation of cross-talk between
      signalling modules in response to single and multiple inputs. To follow up these
      questions there are many good databases that provide an information system on
      regulatory networks. This review aims to find some of the bioinformatics tools
      and websites available to conduct signal transduction research and to discuss the
      representation of databases available for the processes of signalling. The
      databases considered here can provide a well-structured overview on the subject
      and a basis for advanced bioinformatics analysis to interpret the function of
      genomic sequences or to analyse signalling networks within a cell. However, the
      knowledge of most signalling pathways is incomplete and for this reason the
      existing databases will provide insight, but very rarely a more complete picture.

PMID- 14725345
TI  - Signal transduction-related bioinformatics services.
AB  - Signal transduction pathways are crucial for the regulation of a very wide
      variety of cellular functions ranging, for example, from translation to
      intercellular communication, and from metabolism to apoptosis. Protein kinases
      and phosphatases, together with their binding partners, are key players in these
      cascades. They also form a substantial part of the genes in genomes and proteins
      in proteomes in all animals. Signalling can be studied in many different levels
      and ways. This has resulted in large body of publications and Internet services.
      This paper describes open-access databases and software aiming at presenting the
      kind of data available and how to perform bioinformatics analyses.

PMID- 14725346
TI  - Public services from the European Bioinformatics Institute.
AB  - The European Bioinformatics Institute (EBI) provides numerous free-of-charge,
      publicly available bioinformatics services that can be divided into the following
      categories: ftp downloads; data submissions processing and biological database
      production; access to query; analysis and retrieval systems and tools; user
      support; training and education and industry support through EBI's SME program.
      These services are all available at the website. It is imperative that EBI's data
      as well as the tools to analyse it efficiently are made available in a free and
      unambiguous way to the scientific community. An important part of the EBI's
      mission is to make this happen in a fast, reliable and efficient manner. This
      paper serves as a brief introduction to each of these services.

PMID- 14725347
TI  - In silico prediction of the structure of membrane proteins: is it feasible?
AB  - In the 'omic' era, hundreds of genomes are available for protein sequence
      analysis, and some 30 per cent of all sequences are of membrane proteins. Unlike
      globular proteins, a 3D model for membrane proteins can hardly be computed
      starting from the sequence. Why is this so? What can we really compute and with
      what reliability? These and other matters are outlined.

PMID- 14725348
TI  - GeneAnnot: interfacing GeneCards with high-throughput gene expression compendia.
AB  - The interpretation of microarray expression results often includes extensive
      efforts to identify and annotate the gene representatives immobilised on the
      arrays. In this paper we describe the usage of our automatic GeneAnnot system,
      which links between Affymetrix arrays and the rich human gene annotations
      available in GeneCards. We explain GeneCards search options and results display;
      elaborate on the presentation of expression information in GeneCards, including
      both our whole-genome GeneNote project and external expression resources;
      describe the various parameters and displays used by GeneAnnot to assess the
      annotation quality and probeset specificity; and show how to search GeneAnnot and
      GeneNote websites directly.

PMID- 14725349
TI  - Designing microarray oligonucleotide probes.

PMID- 14725350
TI  - Federating data with Information Integrator.
AB  - Information Integrator is an extension to IBM's relational database DB2, which
      uses data federation to provide benefits to molecular biology researchers through
      two unique capabilities: increased flexibility in combining data from disparate
      sources, and SQL access to non-SQL data, easing the task of automating data
      analysis.

PMID- 14725351
TI  - Micelle-associated protein in epoetin formulations: aA risk factor for
      immunogenicity?
AB  - PURPOSE: An upsurge of pure red cell aplasia (PRCA) cases associated with
      subcutaneous treatment with epoetin alpha has been reported. A formulation change
      introduced in 1998 is suspected to be the reason for the induction of antibodies
      that also neutralize the native protein. The aim of this study was to detect the
      mechanism by which the new formulation may induce these antibodies. METHODS:
      Formulations of epoetin were subjected to gel permeation chromatography with UV
      detection, and the fractions were analyzed by an immunoassay for the presence of
      epoetin. RESULTS: The chromatograms showed that Eprex/Erypo contained micelles of
      Tween 80. A minute amount of epoetin (0.008-0.033% of the total epoetin content)
      coeluted with the micelles, as evidenced by ELISA. When 0.03% (w/v) Tween 80,
      corresponding to the concentration in the formulation, was added to the elution
      medium, the percentage of epoetin eluting before the main peak was 0.68%.
      CONCLUSIONS: Eprex/Erypo contains micelle-associated epoetin, which may be a risk
      factor for the development of antibodies against epoetin.

PMID- 14725352
TI  - Effects of spermine-conjugated Bowman-Birk inhibitor (spermine-BBI) on
      carcinogenesis and cholesterol biosynthesis in mice.
AB  - PURPOSE: The goals of the studies reported here were to evaluate the effects of
      the soybean-derived protease inhibitor known as the Bowman-Birk inhibitor (BBI)
      and its spermine-conjugate (spermine-BBI) on the prevention of lung tumorigenesis
      and the reduction of heart disease parameters. METHODS: Both spermine-BBI and
      purified BBI (pBBI), at a dose of 20 mg/kg body weight, were administered as
      intraperitoneal injections to animals treated with the chemical carcinogen 3
      methylcholanthrene (MCA) to determine their effects on chemically induced lung
      tumorigenesis in A/J mice. In addition, the effects of spermine-BBI and pBBI on
      the aortic cholesterol content and the percent ester in the mice were determined.
      RESULTS: The characteristics of the animals in the various treatment groups were
      comparable in terms of behavioral phenomena, weight gain, and lack of deaths
      during the experimental period. Thus, there was no detectable toxicity in
      spermine-BBI-treated mice. Both spermine-BBI and pBBI had a significant
      suppressive effect on MCA-induced lung tumors, with spermine-BBI being more
      effective than pBBI. Spermine-BBI was considerably more effective than pBBI at
      affecting heart-disease-related parameters. The amount of esterified cholesterol
      present in the aortas of mice treated with spermine-BBI was 9% lower than that of
      the controls. Both pBBI and spermine-BBI reduced total cholesterol levels in the
      blood, with pBBI reducing the cholesterol level by 15.5% and spermine-BBI by
      33.3%. CONCLUSIONS: Spermine-BBI can prevent lung carcinogenesis without
      detectable toxic effects; therefore, it is concluded that lung targeting by the
      cationization of polypeptides can be achieved without apparent toxicity. The
      increase in retention of spermine-BBI compared to pBBI in liver tissue may make a
      difference for the heart disease parameters evaluated. Although spermine-BBI is
      capable of reducing the total cholesterol and ester levels in mice, pBBI did not
      have as great an effect on these parameters. Because the liver is the major site
      for the production of cholesterol, the localization of spermine-BBI in liver
      tissue may account for the greater effect of spermine-BBI on blood cholesterol
      levels. Spermine-BBI was administered to animals for only the first 2 months of
      the 4-month assay period before animal sacrifice, so the results suggest that the
      effects of spermine-BBI on the parameters related to heart disease are long
      lasting, as are the effects of both pBBI and spermine-BBI on lung tumorigenesis.

PMID- 14725353
TI  - Biophysical evidence for His57 as a proton-binding site in the mammalian
      intestinal transporter hPepT1.
AB  - PURPOSE: The objective of this study was to provide direct evidence of the
      relative importance of the His57 residue present in transmembrane domain 2 (TMD
      2) and the His121 residue in TMD 4 as proton-binding sites in human PepT1
      (hPepT1) by using a novel mutagenesis approach. METHODS: His57 and His121 in
      hPepT1 were each mutated to alanine, arginine, or lysine individually to obtain
      H57A-, H57R-, H57K-, H121A-, H121R-, and H121K-hPepT1. H7A-hPepT1 was used as a
      negative control. [3H]Glycylsarcosine (Gly-Sar) uptake was measured 72 h
      posttransfection using HEK293 cells individually transfected with these mutated
      proteins. Steady-state I/V curves (-150 mV to +50 mV, holding potential -70 mV)
      were obtained by measuring 5 mM Gly-Sar-induced currents in oocytes expressing H
      57R- and H57K-hPepT1. Noninjected oocytes and wild-type hPepT1 (WT-hPepT1)
      injected oocytes served as negative and positive controls, respectively. RESULTS:
      At pH 6.0, H57K-, H57R-, H121K-, and H121R-hPepT1 led to a 97%, 90%, 45%, and 75%
      decrease in [3H]Gly-Sar uptake into HEK293 cells, respectively. At pH 7.4, uptake
      in cells transfected with H57K- and H57R-hPepT1 was not significantly different
      from that at pH 6.0, whereas cells expressing H121R- and H121K-hPepT1 showed 56%
      and 65% decrease, respectively, compared to that at pH 6.0. In oocytes expressing
      H57R-hPepT1, steady-state currents induced by 5 mM Gly-Sar increased with
      increasing pH (I(max) = 300 nA at pH 8.5), suggesting the binding of protons to
      H57R. No such trend was observed in oocytes injected with H57K, H121R, and H121K
      cRNA. CONCLUSIONS: H57R-hPepT1 is able to bind protons at a relatively basic pH,
      resulting in facilitation of transport of Gly-Sar by hPepT1 at higher pH. Our
      novel approach provides direct evidence that His57 is a principal proton-binding
      site in hPepT1.

PMID- 14725354
TI  - Quantitative biopharmaceutics classification system: the central role of
      dose/solubility ratio.
AB  - PURPOSE: To develop a quantitative biopharmaceutics drug classification system
      (QBCS) based on fundamental parameters controlling rate and extent of absorption.
      METHODS: A simple absorption model that considers transit flow, dissolution, and
      permeation processes stochastically was used to illustrate the primary importance
      of dose/solubility ratio and permeability on drug absorption. Simple mean time
      considerations for dissolution, uptake, and transit were used to identify
      relationships between the extent of absorption and a drug's dissolution and
      permeability characteristics. RESULTS: The QBCS developed relies on a
      (permeability, dose/ solubility ratio) plane with cutoff points 2 x 10(-6)-10(-5)
      cm/s for the permeability and 0.5-1 (unitless) for the dose/solubility ratio
      axes. Permeability estimates, P(app) are derived from Caco-2 studies, and a
      constant intestinal volume content of 250 ml is used to express the
      dose/solubility ratio as a dimensionless quantity, q. A physiologic range of 250
      500 ml was used to account for variability in the intestinal volume. Drugs are
      classified into the four quadrants of the plane around the cutoff points
      according to their P(app), q values, establishing four drug categories. i.e., I
      (P(app) > 10(-5) cm/s, q < or = 0.5), II (P(app) > 10(-5) cm/s, q > 1), III
      (P(app) < 2 x 10(-6) cm/s. q < or = 0.5), and IV (P(app) < 2 x 10(-6) cm/s, q >
      1). A region for borderline drugs (2 x 10(-6) < P(app) < 10(-5) cm/s, 0.5 < q <
      1) was defined too. For category I, complete absorption is anticipated, whereas
      categories II and III exhibit dose/ solubility ratio-limited and permeability
      limited absorption, respectively. For category IV, both permeability and
      dose/solubility ratio are controlling drug absorption. Semiquantitative
      predictions of the extent of absorption were pointed out on the basis of mean
      time considerations for dissolution, uptake, and transit in conjunction with
      drug's dose/solubility ratio and permeability characteristics. A set of 42 drugs
      were classified into the four categories, and the predictions of intestinal drug
      absorption were in accord with the experimental observations. CONCLUSIONS: The
      QBCS provides a basis for compound classification into four explicitly defined
      drug categories using the fundamental biopharmaceutical properties, permeability,
      and dose/solubility ratio. Semiquantitative predictions for the extent of
      absorption are essentially based on these drug properties, which either determine
      or are strongly related to the in vivo kinetics of drug dissolution and
      intestinal wall permeation.

PMID- 14725355
TI  - In vitro simulation of solid-solid dehydration, rehydration, and solidification
      of trehalose dihydrate using thermal and vibrational spectroscopic techniques.
AB  - PURPOSE: The processes of dehydration, rehydration, and solidification of
      trehalose dihydrate were examined to simulate it in the drying and wetting
      states. METHODS: Techniques included differential scanning calorimetry (DSC),
      thermogravimetric analysis (TGA), and Fourier transform infrared (FT-IR)
      microspectroscopy combined with thermal analysis. Trehalose dihydrate was pressed
      on one KBr pellet (IKBr method) or sealed within two KBr pellets (2KBr method)
      for FT-IR measurement. RESULTS: On the DSC thermogram, the shoulder between 60
      degrees C and 80 degrees C represented a transitional change because no weight
      loss occurred in this area of the TGA curve. The endothermic peak at 100 degrees
      C represented dehydration of trehalose dihydrate to anhydrous trehalose; a 9.5%
      weight loss in the TGA curve occurred from 81 degrees C. The thermal-dependent FT
      IR spectra for trehalose dihydrate prepared by the IKBr method changed markedly
      with temperature in the 1800-1500 cm(-1) region during dehydration. IR peak
      intensity at 1687 cm(-1) assigned to the bending vibrational mode of solid-like
      water declined with temperature and decreased sharply at 67 degrees C. Another IR
      peak at 1640 cm(-1) associated with the bending of liquid water increased at 67
      degrees C but disappeared at 79 degrees C as a result of water evaporation. Both
      peaks for the sample prepared by the 2KBr method changed dramatically at 64
      degrees C; peak intensity at 1640 cm(-1) remained constant above 64 degrees C.
      CONCLUSIONS: A new polymorphic transition of trehalose dihydrate was first
      evidenced at 64-67 degrees C from both DSC curves and thermal-related FT-IR
      spectra. This transitional temperature reflected the thermal-dependent
      transformation from solid-like water to liquid water in the trehalose dihydrate
      structure during dehydration. During rehydration, trehalose anhydrate was
      rehydrated to the dihydrate, and liquid water in the dihydrate structure was
      again transformed to solid-like water. The polymorphic transition within this
      temperature range seems to correlate with the bioprotective effect of trehalose
      dihydrate in preserving protein stability.

PMID- 14725356
TI  - Quantitative prediction of the bitterness suppression of elemental diets by
      various flavors using a taste sensor.
AB  - PURPOSE: The purpose of the study was to develop a method for the quantitative
      prediction of the bitterness suppression of elemental diets by various flavors
      and to predict the optimum composition of such elemental diets for oral
      administration using a multichannel taste sensor. METHODS: We examined the
      effects of varying the volume of water used for dilution and of adding varying
      quantities of five flavors (pineapple, apple, milky coffee, powdered green tea,
      and banana) on the bitterness of the elemental diet, Aminoreban EN. Gustatory
      sensation tests with human volunteers (n = 9) and measurements using the
      artificial taste sensor were performed on 50 g Aminoreban EN dissolved in various
      volumes (140), 180, 220, 260, 300, 420, 660, 1140, and 2100 ml) of water, and on
      50 g Aminoreban EN dissolved in 180 ml of water with the addition of 3-9 g of
      various flavors for taste masking. RESULTS: In gustatory sensation tests, the
      relationship between the logarithmic values of the volumes of water used for
      dilution and the bitterness intensity scores awarded by the volunteers proved to
      be linear. The addition of flavors also reduced the bitterness of elemental diets
      in gustatory sensation tests; the magnitude of this effect was, in decreasing
      order, apple, pineapple, milky coffee, powdered green tea, and banana. With the
      artificial taste sensor, large changes of membrane potential in channel 1, caused
      by adsorption (CPA values, corresponding to a bitter aftertaste), were observed
      for Aminoreban EN but not for any of the flavors. There was a good correlation
      between the CPA values in channel 1 and the results of the human gustatory tests,
      indicating that the taste sensor is capable of evaluating not only the bitterness
      of Aminoreban EN itself but also the bitterness-suppressing effect of the five
      flavors, which contained many elements such as organic acids and flavor
      components, and the effect of dilution (by water) on this bitterness. Using
      regression analysis of data derived from the taste sensor and from human
      gustatory data for four representative points, we were able to predict the
      bitterness of 50 g Aminoreban EN solutions diluted with various volumes of water
      (14-300 ml), with or without the addition of a selected flavor. CONCLUSIONS: Even
      though this prediction method does not offer perfect simulation of human taste
      sensations, the artificial taste sensor may be useful for predicting the
      bitterness intensity of elemental diets containing various flavors in the absence
      of results from full gustatory sensation tests.

PMID- 14725357
TI  - Crystallization of D-mannitol in binary mixtures with NaCl: phase diagram and
      polymorphism.
AB  - PURPOSE: To study the crystallization, polymorphism, and phase behavior of D
      mannitol in binary mixtures with NaCl to better understand their interactions in
      frozen aqueous solutions. METHODS: Differential scanning calorimetry, hot-stage
      microscopy, Raman microscopy, and variable-temperature X-ray diffractometry were
      used to characterize D-mannitol-NaCl mixtures. RESULTS: NaCl and D-mannitol
      exhibited significant melt miscibility (up to 7.5% w/w or 0.20 mole fraction of
      NaCl) and a eutectic phase diagram (eutectic composition 7.5% w/w NaCl; eutectic
      temperature 150 degrees C for the alpha and beta polymorphs of D-mannitol and 139
      degrees C for the delta). The presence of NaCl did not prevent mannitol from
      crystallizing but, depending on sample size, affected the polymorph crystallized:
      below 10 mg, delta was obtained; above 100 mg, alpha was obtained. Pure mannitol
      crystallized under the same conditions first as the delta polymorph and then as
      the a polymorph, with the latter nucleating on the former. KCl showed similar
      eutectic points and melt miscibility with D-mannitol as NaCl. LiCl yielded lower
      eutectic melting points, inhibited the crystallization of D-mannitol during
      cooling, and enabled the observation of its glass transition. CONCLUSIONS:
      Despite their structural dissimilarity, significant melt miscibility exists
      between D-mannitol and NaCl. Their phase diagram has been determined and features
      polymorph-dependent eutectic points. NaCl influences the polymorphic behavior of
      mannitol, and the effect is linked to the crystallization of mannitol in two
      polymorphic stages.

PMID- 14725358
TI  - Transdermal delivery of timolol and atenolol using electroporation and
      iontophoresis in combination: a mechanistic approach.
AB  - PURPOSE: The purpose of this work was to study the effect of electroporation on
      iontophoretic transport of two beta-blockers, timolol (lipophilic) and atenolol
      (hydrophilic), and to have a better understanding of the mechanism of
      combination. METHODS: The transdermal delivery of these beta-blockers through
      human stratum corneum was studied in three-compartment diffusion cells. The
      transport of mannitol was evaluated to assess the electroosmotic flow. RESULTS:
      The iontophoretic transport of timolol was decreased by electroporation because
      the high accumulation of the lipophilic cation timolol in the stratum corneum
      resulted in a decrease of electroosmosis. In contrast, electroosmosis was not
      affected by atenolol, and the iontophoretic transport of atenolol was increased
      by electroporation. CONCLUSIONS: Using two different beta-blockers, we showed
      that lipophilicity and positive charges affect the electrotransport of drugs.
      Understanding the effect of the physicochemical properties of the drug, as well
      as the electrical parameters, is thus essential for the optimization of
      transdermal drug delivery by a combination of electroporation and iontophoresis.

PMID- 14725359
TI  - Influence of histidine on the stability and physical properties of a fully human
      antibody in aqueous and solid forms.
AB  - PURPOSE: The aim of the study was to investigate the effect of histidine on the
      stability and physical properties of a fully human anti-IL8 monoclonal antibody
      (ABX-IL8) in aqueous and solid forms. METHODS: Using a fractional factorial
      design, we tested many excipients, including histidine, sucrose, and other
      commonly used excipients, on the stability and physical properties of the
      antibody in both liquid and lyophilized forms. Antibody stability and physical
      properties were evaluated using size-exclusion high-performance liquid
      chromatography (SEC-HPLC), sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), and a viscometer. Residual moisture content was
      determined by coulometric Karl Fischer titrator. Differential scanning
      calorimetry (DSC) was used to detect the glass transition temperatures (Tg) of
      the solid cakes and melting temperatures (Tm) of the antibody in liquid
      formulations. Fourier-transform infrared (FTIR) spectroscopy was used to examine
      the overall secondary structure. RESULTS: Increasing the histidine concentration
      in the bulk solution inhibited the increases of high-molecular-weight (HMW)
      species and aggregates upon lyophilization and storage. In addition, histidine
      bulk enhanced solution stability of the antibody under freezing and thermal
      stress conditions, as evidenced by the lower levels of aggregates. Furthermore,
      histidine reduced viscosity of the antibody solution, which is desirable for the
      manufacture of the dosage form. However, high concentrations of histidine in
      liquid formulations led to coloration of the solution and high levels of
      aggregates on storage at elevated temperature (40 degrees C) after the
      formulations were exposed to stainless steel containers during bulk freezing
      thawing. CONCLUSIONS: Histidine enhanced the stability of ABX-IL8 in both aqueous
      and lyophilized forms. Histidine also improved the physical properties such as
      reducing the solution viscosity. Liquid formulations containing high
      concentrations of histidine should not be stored in stainless steel tanks at
      elevated temperatures.

PMID- 14725360
TI  - Development of a 7-day, 96-well Caco-2 permeability assay with high-throughput
      direct UV compound analysis.
AB  - PURPOSE: The aim was to replace the traditional 21-day Caco-2 permeability
      protocol by a more high-throughput assay. METHODS: Caco-2 cells were seeded at
      high density in 96-well plates in novel cell culture boxes. After 7 days, drug
      permeability studies were performed. Samples were analyzed by a new UV detection
      method. RESULTS: With increased cell seeding density. functional Caco-2
      monolayers with polarized efflux transporters were established after 7 days in 96
      well polycarbonate filter plates in standard medium. For faster feeding and to
      eliminate medium replacement in each individual well, plates were completely
      submerged in medium in novel cell culture boxes, and only medium outside the
      plate was exchanged. For high-throughput sample analysis, a novel UV-transparent
      transport buffer was established that allowed direct quantification of permeated
      drug from its UV absorption. In vitro permeability studies analyzing 22 passively
      absorbed drugs in the new model correlated well with reported human permeability
      values (r2 = 0.8725). CONCLUSIONS: The new 7-day. 96-well Caco-2 permeability
      model tight to UV analysis offers considerable time, cost, and resource savings
      compared to the traditional model. It has a potential for automation and makes it
      possible to determine the permeability of passively diffusing compounds and to
      classify them according to the BCS in a truly medium- to high-throughput mode.

PMID- 14725361
TI  - Dry powder coating of pellets with micronized Eudragit RS for extended drug
      release.
AB  - PURPOSE: To develop a novel powder coating technology for extended-release
      pellets based on the acrylic polymer, Eudragit RS. METHODS: A mixture of
      micronized Eudragit RS plus talc and a liquid feed (plasticizer plus binder
      solution) were sprayed separately onto propranolol hydrochloride-loaded pellets
      in a fluidized bed coater. The coated pellets were heat-cured under different
      conditions (40 degrees C to 60 degrees C, 2 h to 24 h). The coalescence (film
      formation) of the polymer particles was studied via the determination of the
      glass transition and the minimum polymer-softening temperatures (MST). The coated
      pellets were characterized with respect to their morphologic, release, and
      stability properties. RESULTS: The optimum plasticizer type and concentration and
      process temperatures could be identified by the determination of the MST. High
      concentrations of plasticizer (40% based on the polymer) and a thermal treatment
      were necessary to achieve complete film formation and extended drug release.
      Curing the pellets resulted in release profiles, which did not change during
      storage for 3 years. The coated pellets had a smooth, continuous surface and a
      dense film structure after curing. CONCLUSIONS: This novel coating technique
      avoids the use of organic polymer solutions or latex dispersions, has short
      processing times, and results in stable extended-release profiles.

PMID- 14725362
TI  - Radical mechanisms in the radiosterilization of metoprolol tartrate solutions.
AB  - PURPOSE: Study of the radical mechanisms in the radiosterilization of metoprolol
      tartrate aqueous solutions in order to determine the parameters governing its
      radiostability. METHODS: Pulse radiolysis with pseudo-first-order kinetics to
      measure Ihe reaction rate constants of hydrated electrons and hydroxyl radicals
      with metoprolol tartrate. Chemsimul was used to solve the decay kinetics of
      transients and to simulate the radiolysis of metoprolol tartrate solutions.
      RESULTS: Hydrated electrons react with metoprolol and the tartrate ion with rate
      constants of 6.8 x 10(7) M(-1) s(-1) and 1.7 x 10(7) M(-1) s(-1), respectively.
      Hydroxyl radicals react with metoprolol and the tartrate ion with rate constants
      of 5.2 x 10(9) M(-1) s(-1) and 5.5 x 10(8) M(-1) s(-1), respectively. The
      hydroxyl-metoprolol transients are found to scavenge the superoxide anion (5.5 x
      10(10) M(-1) s(-1)), react with oxygen (1.0 x 10(8) M(-1) s(-1)), and follow a
      biradical decay (2.0 x 10(8) M(-1) s(-1). A simplified radical mechanism is used
      to simulate the loss of potency of metoprolol tartrate aqueous solutions during
      radiosterilization. CONCLUSIONS: To decrease the loss of potency of metoprolol
      tartrate. the sterilization dose must be lowered and very high dose rates used.

PMID- 14725363
TI  - Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal
      transit and drug absorption.
AB  - PURPOSE: The aim of the study was to investigate the effect of different
      concentrations of polyethylene glycol 400 (PEG 400) on liquid transit through,
      and ranitidine absorption from, the gastrointestinal tract. METHODS: Six healthy
      male volunteers received, on four separate occasions, 150 mL water containing 150
      mg ranitidine and either 0 (control), 1,2.5, or 5 g PEG 400. The solutions were
      radiolabeled with technetium-99m to allow their gastrointestinal transit to be
      followed using a gamma camera. Urine samples were collected over a 24-h period to
      assess the amount of ranitidine excreted and hence absorbed. RESULTS: No
      significant differences in gastric emptying were noted between the four
      solutions. In contrast, the presence of 1, 2.5, and 5 g PEG 400 reduced the mean
      small intestinal transit times of the solutions by 9, 20, and 23%, respectively,
      against the control. In terms of drug absorption, the mean cumulative amount of
      ranitidine excreted was reduced by 38% in the presence of both 2.5 and 5 g PEG
      400, although it was significantly increased by 41% in the presence of 1 g PEG
      400. CONCLUSIONS: The results show that low concentrations of PEG 400 enhance the
      absorption of ranitidine possibly via modulation of intestinal permeability,
      while high concentrations have a detrimental effect on ranitidine absorption
      presumably via a reduction in the small intestinal transit time.

PMID- 14725364
TI  - In vivo evaluation of an oral salmon calcitonin-delivery system based on a
      thiolated chitosan carrier matrix.
AB  - PURPOSE: To develop and evaluate an oral delivery system for salmon calcitonin.
      METHODS: 2-Iminothiolane was covalently bound to chitosan in order to improve the
      mucoadhesive and cohesive properties of the polymer. The resulting chitosan-TBA
      conjugate (chitosan-4-thiobutylamidine conjugate) was homogenized with salmon
      calcitonin. mannitol, and a chitosan-Bowman-Birk inhibitor conjugate and a
      chitosan-elastatinal conjugate (6.75 + 0.25 + 1 + 1 + 1). Optionally 0.5% (m/m)
      reduced glutathione. used as permeation mediator, was added. Each mixture was
      compressed to 2 mg microtablets and enteric coated with a polymethacrylate.
      Biofeedback studies were performed in rats by oral administration of the delivery
      system and determination of the decrease in plasma calcium level as a function of
      time. RESULTS: Test formulations led to a significant (p < 0.005) decrease in the
      plasma calcium level of the dosed animals in comparison to control tablets being
      based on unmodified chitosan. The addition of glutathione in the tablets led to a
      further improvement in the oral bioavailability of salmon calcitonin with an
      earlier onset of action and a decrease in the calcium level of about 10% for at
      least 10 h. CONCLUSIONS: The combination of mucoadhesive thiolated chitosan,
      chitosan-enzyme-inhibitor conjugates and the permeation mediator glutathione
      seems to represent a promising strategy for the oral delivery of salmon
      calcitonin.

PMID- 14725365
TI  - Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic
      wound healing.
AB  - PURPOSE: To accelerate diabetic wound healing with TGF-beta1 gene delivery system
      using a thermosensitive hydrogel made of a triblock copolymer, PEG-PLGA-PEG.
      METHODS: Two 7 x 7 mm full thickness excisional wounds were created in parallel
      at the back of each genetically diabetic mouse. The hydrogel containing plasmid
      TGF-beta1 was administered to the wound and formed an adhesive film in situ.
      Controls were either untreated or treated with the hydrogel without DNA. We used
      a commercial wound dressing, Humatrix, either with or without DNA, to compare the
      therapeutic effect with the thermosensitive hydrogel. RESULTS: We found that
      thermosensitive hydrogel alone is slightly beneficial for reepithealization at
      early stage of healing (day 1-5), but significantly accelerated
      repithelializaion, increased cell proliferation, and organized collagen were
      observed in the wound bed treated with thermosensitive hydrogel containing
      plasmid TGF-beta1. The accelerated reepithelialization was accompanied with
      enhanced collagen synthesis and more organized extracellular matrix deposition.
      Humatrix alone or with plasmid TGF-beta1, had little effect. CONCLUSIONS:
      Thermosensitive hydrogel made of PEG-PLGA-PEG triblock copolymer provides
      excellent wound dressing activity and delivers plasmid TGF-beta1 to promote wound
      healing in a diabetic mouse model.

PMID- 14725366
TI  - Magnetic resonance imaging for the in vivo evaluation of gastric-retentive
      tablets.
AB  - PURPOSE: To develop a magnetic resonance imaging (MRI) technique for assessing in
      vivo properties of orally ingested gastric-retentive tablets under physiologic
      conditions. METHODS: Tablets with different floating characteristics (tablet A-C)
      were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet
      position and residence time in human volunteers. Optimal Fe3O4 concentration was
      determined in vitro. Intragastric release characteristic of one slow-release
      tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a
      drug model into the tablet. All volunteers underwent MRI in the sitting position.
      Tablet performance was analyzed in terms of relative position of tablet to
      intragastric meal level (with 100% at meal surface), intragastric residence time
      (min) and Gd-DOTA distribution volume (% of meal volume). RESULTS: Intragastric
      tablet floating performance and residence time of tablets (tablet A-D) as well as
      the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI.
      Tablet floating performance was different between the tablets (A, 93%(95 - 9%);
      B, 80%(80 - 68%): C, 38%(63 - 32%); p < 0.05). The intragastric distribution
      volume of Gd-DOTA was 19.9% proximally and 35.5% distally. CONCLUSIONS: The use
      of MRI allows the assessment of galenic properties of orally ingested tablets in
      humans in seated position.

PMID- 14725367
TI  - Controlled release of insulin from injectable biodegradable triblock copolymer
      depot in ZDF rats.
AB  - PURPOSE: The purpose of this study was to design sustained release system which
      provides basal insulin release over a week by one injection in diabetic animals.
      For an effective injectable formulation and controlled release of insulin, a
      water soluble biodegradable triblock copolymer of PLGA-PEG-PLGA was used.
      METHODS: For in vitro release, samples were analyzed by reversed-phase high
      performance liquid chromatography. Animal studies using ZDF rats have been
      conducted to demonstrate the bioactivity of the released insulin. Insulin
      formulation was injected subcutaneously. At designated times, the blood glucose
      levels and insulin levels of the ZDF rats were measured. RESULTS: The in vitro
      release of zinc-complexed insulin showed no initial burst and demonstrated
      constant release rate with the duration of 14 days. Constant steady state plasma
      levels of exogenous insulin were detected for nearly two weeks indicating
      constant rate of insulin release in vivo upon single subcutaneous injection.
      CONCLUSIONS: We conclude that it is feasible to achieve basal insulin levels over
      a week by a single injection of ReGel formulation. This will provide various
      advantages, including depot formation without surgery, easy sterilization,
      straightforward drug loading, simple dose adjustment, system biocompatibility
      with no inflammatory reaction, and no requirement of using organic solvents.

PMID- 14725368
TI  - Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the
      branched polyesters, DEAPA-PVAL-g-PLGA.
AB  - PURPOSE: This study describes the development of surfactant-free, biodegradable
      nanoparticle systems with varying physicochemical properties and their
      suitability for pulmonary application via nebulization. METHODS: Nanoparticle
      suspensions were formulated from the branched polyester, diethylaminopropyl amine
      poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide) (DEAPA-PVAL-g-PLGA) alone,
      as well as with increasing amounts of carboxymethyl cellulose (CMC). Particle
      size, zeta potential, turbidity, and morphology (atomic force microscopy) were
      characterized. Three formulations were chosen for further study: Cationic
      nanoparticles without CMC, cationic nanoparticles with CMC, and anionic
      nanoparticles with an excess of CMC. Nanoparticle degradation was characterized,
      as well as stability during nebulization. Nanoparticle-cell interactions were
      investigated and quantified using confocal laser scanning microscopy and
      fluorescence spectrometry. RESULTS: Nanoparticles ranged in size from 70-250 nm
      and displayed zeta potentials of +58.9 to -46.6 mV. Anionic nanoparticles showed
      the highest stability during nebulization. The degradation rate of each
      nanoparticle formulation decreased with increasing amounts of CMC. Cell
      association was highest among cationic nanoparticles (57% and 30%, respectively),
      although these were not internalized. Despite a lower rate of cell association
      (3%), anionic nanoparticles were internalized by A549 cells. CONCLUSIONS:
      Surfactant-free nanoparticles from DEAPA-PVAL-g-PLGA are versatile drug delivery
      systems; however, only the anionic formulations investigated were proven suitable
      for aerosol therapy.

PMID- 14725369
TI  - Novel polymeric micelles of amphiphilic triblock copolymer poly (p-dioxanone-co-L
      lactide)-block-poly (ethylene glycol).
AB  - PURPOSE: The objective of this study is to characterize the micelles of novel
      block copolymer of poly (p-Dioxanone-co-L-Lactide)-block-Poly (ethylene glycol)
      (PPDO/PLLA-b-PEG-) and evaluate its ability to induce gene transfection. METHODS:
      The ability of the block copolymer to self-assemble was determined by
      viscometery, dye solublization, NMR spectra and dynamic light scattering. The
      Trypan blue assay for in vitro biocompatibility of the block copolymer was
      carried out with NIH 3T3, CT-26 and MCF-7 cells, and beta-glactosidase assay was
      applied to measure the transfection efficiency of the block copolymer on MCF-7
      breast cancer cell. RESULTS: Depending on the block lengths and molecular
      weights, solubility of the polymeric samples in water was varied. Diluted aqueous
      solution properties of the copolymer were studied. 1,6-Diphenyl-1,3,5-hexatriene
      solubilization and 1H NMR spectra carried out in CDCl3 and D2O, were used to
      prove the existence of hydrophobic domains as the core of micelle. Average
      particle size of 60-165 nm with low polydispersity, and lower negative zeta
      potential of -3 to -14 mV were observed on the aqueous copolymer dispersion.
      Copolymer was found with almost no cytotoxic effect and was able to promote the
      transfection efficiency (about 3-fold) in MCF-7 cells. CONCLUSIONS: The PPDO/PLLA
      b-PEG copolymer has ability to assemble into nanoscopic structures in aqueous
      environment, which enable to enhance gene transfection.

PMID- 14725370
TI  - Generation of fine powders of recombinant human deoxyribonuclease using the
      aerosol solvent extraction system.
AB  - PURPOSE: To investigate the feasibility of using the Aerosol Solvent Extraction
      System (ASES) to produce fine powders of recombinant human deoxyribonuclease
      (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based
      solutions. METHODS: The ASES technique using high pressure carbon dioxide
      modified with ethanol or ethanol and triethylamine was used for the generation of
      rhDNase powders and protein-lactose powders from aqueous based solutions.
      Particle size, morphology, size distributions, crystallinity, and powder aerosol
      performance were measured. The biochemical integrity of the processed rhDNase was
      assessed by testing the monomer content and the degree of deamidation. RESULTS:
      RhDNase precipitated as spherical particles in the size range between 50 and 500
      nm. The primary nano-sized particles were agglomerated to micron-sized clumps of
      particles during the precipitation process. The median particle size and the fine
      particle fraction were functions of the operating temperature and the nozzle
      system used. RhDNase was substantially denatured in the ASES process using carbon
      dioxide modified with ethanol as anti-solvent. However almost complete recovery
      of the monomer was achieved using carbon dioxide modified with ethanol
      triethylamine as an anti-solvent. Lysozyme-lactose and rhDNase-lactose powders
      were also precipitated as agglomerated spheres using the ASES process. The
      powders were amorphous except for those with lactose content higher than 45%.
      CONCLUSIONS: Micron-sized particles of rhDNase suitable for inhalation delivery
      were generated from aqueous based solutions using the modified ASES technique.
      The biochemical integrity of the rhDNase powder is a function of the antisolvent
      and the operating temperature.

PMID- 14725372
TI  - Perceptions and use of dental quacks (unqualified dental practitioners) and self
      rated oral health in Trinidad.
AB  - OBJECTIVE: To investigate reasons for use of dental quacks, treatment received,
      satisfaction with treatment, perceived differences to qualified dentists, and
      relationships to sociodemographic factors and self rated oral health. METHOD: A
      14-item questionnaire including closed and open questions, was administered by
      interview to adult patients attending government health centres in Trinidad.
      RESULTS: Data were collected between November 2001 and March 2002. Two hundred
      and two people from 273 invited to participate, were interviewed (response rate
      74%). Sixty seven per cent reported visiting a dental quack. People who had used
      a quack were older, from lower socioeconomic groups and more likely to be living
      in an area where there were fewer government dental clinics. The most common
      reason for visiting a quack was toothache (74%) and extraction was the most
      common treatment received (61%). Forty three per cent of respondents were
      dissatisfied with the treatment received from a quack and 83% felt that treatment
      provided by a qualified dentist was different. Main reasons for using a quack
      were cost (53%) and availability (20%). People who had used a quack were less
      likely to rate their oral health as 'Very good' or 'Excellent'. CONCLUSION: Those
      using the services of dental quacks in Trinidad were more likely to have lower,
      self rated oral health. Affordability and availability of dental treatment were
      identified as barriers to care from qualified dentists.

PMID- 14725371
TI  - Effects of high hydrostatic pressure on several sensitive therapeutic molecules
      and a soft nanodispersed drug delivery system.
AB  - PURPOSE: According to the development in the last decade of industrial processes
      using high hydrostatic pressure (HHP) for preservation of several commercial food
      products, novel sterilization or decontamination processes for pharmaceutical
      products could be conceivable. The aim of this work is to evaluate the effects of
      HHP on the integrity of insulin and heparin solutions, suspension of monoclonal
      antibodies and Spherulites. METHODS: High performance liquid chromatography, thin
      layer chromatography, capillary electrophoresis assays, ELISA tests, laser
      granulometry and spectrophotometry analyses have been performed to compare HHP
      treated drugs (in a domain of pressure and temperature ranging respectively from
      20 up to 500 MPa and from 20 degrees C up to 37 degrees C) vs. untreated ones.
      RESULTS: No difference has been detected except for monoclonal antibodies that
      are altered above 500 MPa. CONCLUSIONS: The structure integrity of sensitive
      molecule due to the small energy involved by HHP and the development of
      industrial plants (intended for the decontamination of food products) confer to
      this technology the potential of a new method for sterilization of fragile drugs
      and an original alternative to aseptic processes and sterilizing filtration.

PMID- 14725373
TI  - Restorative service patterns in Australia: amalgam, composite resin and glass
      ionomer restorations.
AB  - AIM: To examine the provision of amalgam, composite resin and glass ionomer
      restorations, and to assess whether these main restorative services varied by
      patient, visit and oral health characteristics. DESIGN: A cross-sectional survey
      incorporating a log of service items provided on a typical day. SETTING:
      Australian private general practice. METHODS: Data on services and patients were
      collected by a mailed survey from a random sample of dentists from each
      State/Territory in Australia in 1998-99 with a response rate of 71%. MAIN OUTCOME
      MEASURES: Rates per visit of amalgam, composite resin and glass ionomer
      restorations among dentate adults who had received a restoration. RESULTS:
      Analysis showed older patients had lower amalgam rates but higher glass ionomer
      rates, composite resin rates were lower at emergency visits, capital city
      patients had higher amalgam rates but lower composite resin rates, patients with
      decayed teeth had higher amalgam and composite resin rates, and use of
      restorative materials varied by clinical problem. CONCLUSIONS: Despite widespread
      use of alternative materials, amalgam rates remained high in circumstances such
      as replacement restorations and restorations involving more than one surface.
      Other restorative materials also had specific applications. Both amalgam and
      composite resins were provided at higher rates to patients with active caries but
      composite resins were also used at higher rates for aesthetic problems. Glass
      ionomer restorations were used at higher rates for initial and one-surface
      restorations, and for conditions such as root caries and dentinal sensitivity.

PMID- 14725374
TI  - Dental amalgam and human health.
AB  - The use of dental amalgam as a restorative material has long been a contentious
      issue because of its elemental mercury component. While microleakage of mercury
      from amalgam has been conclusively confirmed over the past 30 years intensive
      research has failed to identify deleterious health outcomes. Mercury, as with
      other metals entering the body tissues, appears to be tolerated at low levels.
      Nevertheless, a contrary opinion is held by some professional and lay groups who
      advocate a zero tolerance for inhaled or ingested elemental mercury. They
      identify dental amalgam as an aetiological factor for neurological conditions
      such as chronic fatigue syndrome, multiple sclerosis and Alzheimer's disease
      resulting from chronic mercury poisoning. Epidemiological and clinical evidence
      of widespread chronic mercury toxicity associated with a body burden of amalgam
      has consistently failed to be established even in populations with a high
      prevalence of dental amalgam restorations. On current evidence, international
      consensus heavily supports the statement that amalgam does not constitute a
      health risk to patients. However, exposure to volatile free mercury in dental
      clinics should be controlled to eliminate occupational risk. This paper provides
      a general review of the current situation and issues. It offers a consensus
      viewpoint for practitioners and lay people in reaching an informed decision on
      dental amalgam restorations.

PMID- 14725375
TI  - Licensing exams in dentistry Israel 1996-2001.
AB  - AIMS AND OBJECTIVES: To describe the experiences with licensing exams in the
      years 1996-2001 for the Dentist Ordinance in Israel, an exam which it is required
      for each candidate to pass before being allowed to practice. SUBJECTS: The
      candidates in large numbers and with a wide variety of professional education
      applying to take the exam in dentistry in Israel. RESULTS: The exams are
      conducted in several languages and consist of two parts. 3,612 candidates were
      examined for Part I, out of which 1,598 passed (44%), while 3,298 candidates were
      examined for Part II, and 1,558 passed (47%). CONCLUSION: It is feasible and
      practical to conduct uniform exams for a multinational group of candidates from
      various dental educational backgrounds in several languages and in large numbers.

PMID- 14725376
TI  - Gender issues and oral health in elderly Indians.
AB  - OBJECTIVES: Gender disparity in health and diseases is increasingly being
      recognised. Therefore, it was decided to investigate gender differences in the
      elderly subjects (60+years) from a community-based study. The study was
      undertaken to evaluate the oral health status and treatment needs of urban and
      rural elderly and to study the impact of socio-demographic variables on them.
      STUDY DESIGN: An urban area in South Delhi and its adjoining four villages was
      selected. A modified WHO-Oral Health Survey proforma and Rup-Nagpal's scale were
      used to record oral health and socio-demographic data respectively. In addition,
      diet pattern (vegetarian/non-vegetarian) and body mass index (BMI) were also
      recorded. Chi square test and p values were calculated for each of the studied
      parameters. RESULTS: There were significant differences for socio-economic
      status, literacy level, marital and family status between elderly men and women
      (p<0.0001). A higher percentage of elderly women were vegetarian and overweight
      than elderly men (p<0.01). However, there were few differences found in the
      prevalence of dental caries, periodontal diseases and edentulousness between male
      and female elderly (p>0.01). The only difference found was in the evidence of
      previous dental treatment received. Elderly men had a higher percentage of filled
      teeth and denture wear compared to elderly women (p<0.01). CONCLUSIONS: Women's
      oral health is significantly influenced by social, economic and psychological
      factors.

PMID- 14725377
TI  - Influence of diagnostic adjuncts to the measurement of caries prevalence at
      different caries thresholds.
AB  - OBJECTIVES: To determine the influence of diagnostic adjuncts (dental brushing
      and drying) in dental caries diagnosis. To analyse the underestimation levels in
      epidemiological examinations when compared to traditional dental setting
      examinations. To evaluate the influence of including noncavitated (NC) carious
      lesions in the estimation of the disease. PARTICIPANTS: 51, 12-year-old children.
      INTERVENTIONS/METHODS: Four epidemiological exams performed in an outdoor setting
      and one performed in a traditional dental setting (visual-tactile method
      associated or not with diagnostic adjuncts). MAIN OUTCOME MEASURES: DMFS
      (Decayed, Missing and Filled Surfaces) index, according to the WHO criteria.
      RESULTS: When compared to exams carried out in a traditional dental setting, the
      epidemiological examinations showed no significant statistical differences for
      the DMFS score (p>0.05), presenting underestimation levels lower than 10% (except
      for the low prevalence caries group in the WHO exam). For the DMFS, previous
      dental brushing was more relevant than previous dental drying, although drying
      was the most important resource for NC diagnosis (p<0.05). CONCLUSION: The
      visual/tactile method, with or without diagnostic adjuncts, can diagnose
      cavitated lesions efficiently, but not NC lesions. However, for the low caries
      prevalence group, the implementation of dental brushing prior to an exam could be
      suggested.

PMID- 14725378
TI  - A survey of the correspondence between abrasions and tooth brushing habits in
      Erzurum, Turkey.
AB  - AIM: To determine whether there is a correlation between dental abrasions and the
      frequency and technique of tooth brushing, as well as to examine the prevalence
      of dental abrasion according to age and gender. MATERIALS AND METHODS: This study
      was carried out on 428 adults (242 female, 186 male) 20 years of age and older,
      who attended the Department of Operative Dentistry, Department of Oral Diagnosis
      and Oral Radiology Faculty of Dentistry, Ataturk University. RESULTS: The study
      revealed a statistically significant relationship between abrasive lesions and
      age groups as well as between abrasive lesions and gender. A statistically
      significant difference was determined between abrasions and tooth brushing
      frequency, while there was no statistically significant relation between
      abrasions and tooth brushing technique (p>0.05). CONCLUSION: The prevalence of
      tooth brushing abrasions increases with age, and lesions are seen more frequently
      in males than in females. Also, tooth brushing technique is not important to the
      presence of abrasions, but increased tooth brushing frequency results in an
      increase in the number of abrasions.

PMID- 14725379
TI  - The oral environment: the challenge for antimicrobials in oral care products.
AB  - For any antibacterial/ anti-plaque system from an oral care product to be
      effective, it must firstly be delivered and retained at relevant sites in the
      oral cavity and secondly, remain active within the chosen formulation to
      successfully target the biofilm cells within dental plaque. This must include
      inhibition of the growth and metabolism of relevant organisms associated with
      disease. This review will concentrate on understanding the environmental
      conditions in which such oral care products must work and summarise the activity
      within the oral cavity of the main antibacterial and anti-plaque agents in common
      oral care products, namely chlorhexidine, essential oils, metal salts and
      Triclosan. Routes to further enhance the activity of these products, together
      with the use of relatively novel formats such as confectionery products to
      provide added consumer oral health benefits will be considered.

PMID- 14725380
TI  - Anti-microbial efficacy and mode of action studies on a new zinc/ Triclosan
      formulation.
AB  - OBJECTIVE: To test in vitro the anti-plaque/ antimicrobial efficacy of a new
      toothpaste formulation containing a 2% zinc citrate/ 0.3% Triclosan anti
      microbial system compared with a 0.75% zinc citrate/ 0.3% Triclosan system and
      where appropriate, against controls of a standard fluoride paste and a 0.3%
      Triclosan/ 2% copolymer product. METHODS: The anti-metabolic activity was
      assessed using a range of assays measuring the ability of the active systems to
      inhibit bacterial glycolysis. The antibacterial/ anti-plaque activity was
      assessed in an in vitro multispecies biofilm assay. RESULTS: Both zinc
      formulations were shown to have significantly superior activity at inhibiting
      glycolysis compared with the 0.3% Triclosan/ 2% copolymer formulation and the
      standard fluoride paste, particularly in reducing the pH drop after sugar
      challenge, the new formulation having the greatest activity. Likewise, in the
      antibacterial assay, both zinc formulations were found to have significantly
      superior activity over a standard fluoride paste and the 2% zinc citrate/ 0.3%
      Triclosan formulation was shown to be significantly better than 0.75% zinc
      citrate/ 0.3% Triclosan formulation. CONCLUSION: These data provide support for
      the enhanced performance of the 2% zinc citrate/ 0.3% Triclosan formulation.

PMID- 14725381
TI  - Antimicrobial effects of a novel Triclosan/zinc citrate dentifrice against mixed
      culture oral biofilms.
AB  - AIM: To compare the antimicrobial efficacy in vitro of a new fluoride system
      containing 0.3% Triclosan and 2.0% zinc citrate with a standard fluoride
      toothpaste against bacteria commonly isolated from dental plaque. METHOD: Mature
      biofilms of fixed depth containing ten oral bacterial species were developed in a
      model system and then exposed to the formulations both in situ and ex situ.
      RESULTS: The standard fluoride toothpaste had limited activity against the Gram
      positive species following 1 and 5 minutes ex situ exposure (p = 0.004 and p =
      0.02, respectively) but none against the Gram negative species; also, no overall
      effect following repeated pulsing in situ was observed. In contrast, viable
      counts of Gram positive and Gram negative species were markedly reduced following
      ex situ exposure for 1 and 5 minutes to the new formulation (Gram positive: p =
      0.0007 and p = 0.04; Gram negative: p = 0.04 and p = 0.00001, respectively).
      Counts of Gram positive bacteria were reduced by 99.9% over a 4-day in situ
      pulsing period, while no Gram negative species were recoverable from the biofilm
      by day 4. CONCLUSION: The new toothpaste formulation had a broad spectrum of
      antimicrobial activity against biofilm consortia containing bacteria associated
      with both dental caries and periodontal diseases.

PMID- 14725382
TI  - Plaque antibacterial levels following controlled food intake and use of a
      toothpaste containing 2% zinc citrate and 0.3% Triclosan.
AB  - OBJECTIVES: To measure the levels of zinc and Triclosan present in plaque 12
      hours post-brushing and following two weeks home use of a toothpaste formulation
      containing 2% zinc citrate and 0.3% Triclosan. To measure the levels of zinc and
      Triclosan in plaque following two weeks home use of the test toothpaste
      formulation together with a further morning's brushing and a day of controlled
      food intake. METHODS: A total of 104 subjects completed the study. Plaque samples
      were taken before use of the test toothpaste and again after a specified regime
      of product use and food intake. The samples were analysed for zinc or Triclosan.
      RESULTS: Levels of zinc and Triclosan in plaque 12 hours after last brushing and
      following a 2-week home usage of product, were 149.1 microg/g and 8.6 microg/g
      respectively. Following a morning brushing and a day of controlled food intake
      zinc and Triclosan levels were 94.7 microg/g and 4.1 microg/g respectively. These
      levels of agents were found to reduce pH drop in vitro. CONCLUSIONS: Regular use
      of a toothpaste containing 2% zinc citrate and 0.3% Triclosan can lead to a build
      up of antibacterial agents in plaque that continue to work even after controlled
      food intake.

PMID- 14725383
TI  - The effect of a 2% zinc citrate, 0.3% Triclosan dentifrice on plaque acid
      production following consumption of a snackfood.
AB  - OBJECTIVES: A) To assess plaque lactate production following consumption of three
      foods (cake, chocolate/caramel bar, sweetened coffee), and B) To measure the
      effect of a fluoride dentifrice containing 2% zinc citrate and 0.3% Triclosan on
      plaque lactate and pH drop following consumption of cake. METHODS: A) 10 subjects
      completed the first study. Plaque samples taken before and at 8,15 and 30 minutes
      after eating. Samples were analysed for lactate via Capillary Electrophoresis. B)
      30 subjects completed the second study. Plaque samples were taken before and
      after cake and use of test dentifrice or no treatment control. Plaque pH and
      lactate content were assessed. RESULTS: A) Plaque lactate levels increased after
      all three foods; peak lactate levels occurred 8 minutes after eating. B) Plaque
      lactate concentrations after eating cake were 39.2mM for the control treatment
      and a significantly lower value, 23.6mM, for the test 2% zinc citrate, 0.3%
      Triclosan dentifrice. After food challenge, pH values were 5.53 for the no
      treatment group and a significantly higher value of 5.79 for the test dentifrice
      group. CONCLUSIONS: A toothpaste containing 2% zinc citrate, 0.3% Triclosan can
      significantly reduce plaque lactate generation and pH drop induced by cake,
      compared to no treatment control.

PMID- 14725384
TI  - The effect of a toothpaste containing 2% zinc citrate/0.3% Triclosan on the
      glycolysis of plaque bacteria ex vivo after food intake.
AB  - OBJECTIVE: To develop an ex vivo plaque pH method to assess the efficacy of a new
      zinc citrate/Triclosan formulation. METHODS: Study (1) focussed on method
      development. Study (2) examined the effect of a toothpaste containing 2% zinc
      citrate/0.3% Triclosan on the pH of plaque after product use and consumption of
      pizza. Study (3) investigated the effect of the same formulation and a fluoride
      toothpaste on the pH of plaque without an 'eating occasion'. The pH of plaque
      samples was measured over 10 minutes in the presence of glucose. RESULTS: The
      test product significantly reduced the amount of acid produced 30 minutes (p =
      0.0035) and 3 hours (p = 0.0018) after brushing (study (2)). In study (3) use of
      the test product significantly reduced the amount of acid produced 3 hours after
      brushing (p = 0.0023). No significant benefit was found for the fluoride
      toothpaste. CONCLUSION: An ex vivo plaque pH method has been developed which can
      detect changes in acid produced following brushing with different toothpastes. A
      toothpaste containing 2% zinc citrate/0.3% Triclosan significantly reduced the
      total acid produced for at least 3 hours after product use. Moreover it has been
      demonstrated that this effect is detectable even after eating.

PMID- 14725386
TI  - The effect of oral care feed-back devices on plaque removal and attitudes towards
      oral care.
AB  - OBJECTIVES: Two studies were carried out to investigate whether the effect of
      specific oral care feed-back devices would result in better plaque removal (Study
      1) and lead to changes in attitudes and views relating to oral health (Study 2).
      The objective of the first study was to compare the ability of a toothbrush
      system consisting of a new toothbrush plus plaque disclosing tablet (SIGNAL
      Integral) to remove supra-gingival plaque to that of a marketed toothbrush (Oral
      B Cross Action) following a single unsupervised brushing. METHODS: Study 1 had a
      cross-over design and included 21 healthy adult volunteers. Subjects refrained
      from any form of oral hygiene for 24 hours prior to each test session. Plaque
      levels (Modified Quigley-Hein Plaque index) were assessed prior to and following
      each unsupervised brushing. When the new toothbrush was used, subjects self
      disclosed their plaque with a disclosing tablet (erythrosine) immediately prior
      to brushing. At each occasion, brushing time (in sec) was also recorded. Study 2
      had a two-cell, parallel design (test and control group) and lasted for five
      days. Healthy adult volunteers were enrolled. Subjects in the test group (n = 30)
      were given a fluoride toothpaste and four saliva test strips to use at home. The
      saliva test strip is designed to change colour in the pH range of 6.5 to 10,
      allowing the user to verify the effect of brushing. The control group (n = 29)
      received no saliva test strips. Subjects completed a questionnaire after 4 days
      of product use. RESULTS: In Study 1, significantly more plaque was removed (p <
      0.05) and brushing time was increased by more than 20% when subjects used the new
      toothbrush together with the disclosing tablet compared to brushing with the
      marketed toothbrush. In Study 2, significant increases in motivation relating to
      oral hygiene were found in the test group who had been using the saliva test
      strip. CONCLUSION: The two studies have provided significant evidence that the
      provision of feed-back devices in an oral care context can lead to improved
      removal of plaque and increased motivation.

PMID- 14725385
TI  - The effect of a toothpaste containing 2% zinc citrate and 0.3% Triclosan on
      bacterial viability and plaque growth in vivo compared to a toothpaste containing
      0.3% Triclosan and 2% copolymer.
AB  - OBJECTIVE: To compare the antimicrobial efficacy and effect on plaque growth of a
      new silica-based fluoride toothpaste containing 2% zinc citrate/ 0.3% Triclosan
      with a silica-based fluoride toothpaste containing 0.3% Triclosan/2% copolymer.
      METHODS: In Study 1, plaque was collected after one week's use of each toothpaste
      and assessed for bacterial viability, live/ dead ratio and microbial membrane
      integrity. In study 2, plaque was measured immediately and 18 hours after a
      single brushing with the specified toothpastes. RESULTS: The 2% zinc citrate/0.3%
      Triclosan formulation significantly reduced the total number of viable aerobic
      and anaerobic bacteria (p = 0.0223 and p = 0.0443 respectively) compared to the
      0.3% Triclosan/2% copolymer formulation. Both toothpastes increased the bacterial
      membrane permeability significantly. However, the proportion of live bacteria for
      the 2% zinc citrate/0.3% Triclosan product was significantly reduced (p < 0.05).
      Study 2 showed significantly less plaque growth 18 hours after using the 2% zinc
      citrate/0.3% Triclosan toothpaste compared to the 0.3% Triclosan/2% copolymer
      toothpaste (p < 0.01). CONCLUSION: Regular use of a fluoride toothpaste
      containing 2% zinc citrate and 0.3% Triclosan, significantly reduced the
      viability of plaque bacteria compared to a fluoride toothpaste containing 0.3%
      Triclosan/ 2% copolymer 12 hours after brushing. In addition, a clinical plaque
      growth study confirmed that this anti-microbial efficacy leads to a significant
      reduction in plaque growth.

PMID- 14725387
TI  - Writing in the first person--time to change.

PMID- 14725388
TI  - The sound of silence--nurses' non-verbal interaction within the ward round.
AB  - This study describes nurses' non-verbal interaction in the ward round within
      intensive care. Data were collected through participant observation, fieldwork
      notes and ethnographic interview techniques from eight intensive care nurses.
      This article focuses on the themes 'Being there', 'Knowing the script', 'Knowing
      what you want from the ward round' and 'Silencing and gaze', which emerged from
      the data. A key issue highlighted in this study is that nurses need to recognize
      their contribution to patient management decisions within the ward round. Drawing
      from the data, educational and training strategies are suggested to enhance
      collaborative practice in the clinical setting of intensive care.

PMID- 14725389
TI  - An evaluation of critical care lecturer practitioners.
AB  - The aim of this study was to evaluate the educational value and impact upon staff
      of critical care lecturer practitioners. Data were collected through three staff
      focus groups (n=21) and a questionnaire completed by 70 members of trust or
      university staff. A majority of respondents felt that the lecturer practitioner
      roles had considerable effect upon adult critical care services. Six main
      categories of findings were derived from analysis and integration of both focus
      group and questionnaire data--development of knowledge; staff support; being a
      teacher; developing and maintaining the workforce; role improvement plus removal
      of the lecturer practitioner role. Many of these findings concur with the limited
      quantity of evaluative literature on the lecturer practitioner role. The authors
      produced a report recommending continued funding for existing lecturer
      practitioner posts; introduction of more lecturer practitioner posts should be
      considered, and further role evaluation should be conducted at both a local and
      national level.

PMID- 14725390
TI  - Care bundles in critical care: a practical approach to evidence-based practice.
AB  - The care bundle is a new concept in critical care, which is currently being
      promoted by the National Health Service Modernisation Agency for Critical Care.
      Care bundles originated in North America and are described best as groups of
      evidence-based practice interventions. The theory behind care bundles is that
      when several evidence-based interventions are grouped together in a single
      protocol, it will improve patient outcome. Care bundles are relatively easy to
      develop, implement and audit, and provide practitioners with a practical method
      for implementing evidence-based practice. This article describes the care bundle
      and offers practical suggestions about how to develop, implement and audit them
      in practice.

PMID- 14725391
TI  - Life review following critical illness in young men.
AB  - Surviving events that have posed a serious threat to life can result in major
      psychological problems during the recovery period. Younger patients, with years
      of life ahead of them, are at risk of depression and loss of self-esteem
      following their ordeal, despite their physical recovery. Traditional forms of
      counselling and psychotherapy following traumatic events can sometimes carry a
      stigma and be viewed as 'disease centred'. Reminiscence and life review
      therapies, used until now, with the elderly, appear to have valuable transferable
      benefits to younger survivors of critical illness. Life review and reminiscent
      interventions are holistic and person centred, techniques resonating with the
      essence of critical care nursing. Life review and reminiscence can be used
      therapeutically from an early stage to help minimize the negative psychological
      effects of being critically ill.

PMID- 14725392
TI  - Device for convenient measurement of spatially varying bidirectional reflectance.
AB  - Capturing surface appearance is a challenging task because reflectance varies as
      a function of viewing and illumination direction. In addition, most real-world
      surfaces have a textured appearance, so reflectance also varies spatially. We
      present a texture camera that can conveniently capture spatially varying
      reflectance on a surface. Unlike other bidirectional imaging devices, the design
      eliminates the need for complex mechanical apparatus to move the light source and
      the camera over a hemisphere of possible directions. To facilitate fast and
      convenient measurement, the device uses a curved mirror so that multiple views of
      the same surface point are captured simultaneously. Simple planar motions of the
      imaging components also permit change of illumination direction and region
      imaging. We present the current prototype of this device, imaging results, and an
      analysis of the important imaging properties.

PMID- 14725393
TI  - Spectral-daylight recovery by use of only a few sensors.
AB  - Linear models have already been proved accurate enough to recover spectral
      functions. We have resorted to such linear models to recover spectral daylight
      with the response of no more than a few real sensors. We performed an exhaustive
      search to obtain the best set of Gaussian sensors with a combination of optimum
      spectral position and bandwidth. We also examined to what extent the accuracy of
      daylight estimation depends on the number of sensors and their spectral
      properties. A set of 2600 daylight spectra [J. Opt. Soc. Am. A 18, 1325 (2001)]
      were used to determine the basis functions in the linear model and also to
      evaluate the accuracy of the search. The estimated spectra are compared with the
      original ones for different spectral daylight and skylight sets of data within
      the visible spectrum. Spectral similarity, colorimetric differences, and
      integrated spectral irradiance errors were all taken into account. We compare our
      best results with those obtained by using a commercial CCD, revealing the CCD's
      potential as a daylight-estimation device.

PMID- 14725394
TI  - Asymptotic behavior and inverse problem in layered scattering media.
AB  - The main challenge of noninvasive optical biopsy is to obtain an accurate value
      of the optical coefficients of an encapsulated organ (muscle, brain, etc.). The
      idea developed by us is that some interesting information could be deduced from
      the long-time behavior of the reflectance function. This asymptotic behavior is
      analyzed for layered media in the framework of the diffusion approximation. A new
      method is derived to obtain accurate values for the optical parameters of the
      deepest layers. This method is designed to work in a specific long-time regime
      that is still within the scope of standard time-of-flight experiments but far
      from being included in the mathematically defined asymptotic region. The limits
      of this method, linked to the cases where the asymptotic behavior is no longer
      governed by the deepest layer, are then discussed.

PMID- 14725395
TI  - One-dimensional inverse scattering with a Born model in a three-layered medium.
AB  - We deal with the inverse-scattering problem for a dielectric slab embedded in a
      three-layered medium starting from multifrequency scattered field data under the
      framework of the Born approximation. This allows us to state the problem as a
      linear inverse one, and the singular-value decomposition (SVD) of the relevant
      operator makes it possible to investigate and to solve it. In particular, the SVD
      tool allows an analysis of the reconstruction capabilities of the algorithm in
      terms of spatial variability of the unknowns that can be retrieved. The new
      contribution consists in an analysis of the role of the discontinuity of the
      dielectric properties between the second and the third medium. This analysis is
      performed with regard both to the class of retrievable dielectric profiles and to
      the model error deriving from the Born approximation and shows, finally, that
      this discontinuity can be troublesome.

PMID- 14725396
TI  - Factorization of products of discontinuous functions applied to Fourier-Bessel
      basis.
AB  - The factorization rules of Li [J. Opt. Soc. Am. A 13, 1870 (1996)] are
      generalized to a cylindrical geometry requiring the use of a Bessel function
      basis. A theoretical study confirms the validity of the Laurent rule when a
      product of two continuous functions or of one continuous and one discontinuous
      function is factorized. The necessity of applying the so-called inverse rule in
      factorizing a continuous product of two discontinuous functions in a truncated
      basis is demonstrated theoretically and numerically.

PMID- 14725397
TI  - Computation of quasi-discrete Hankel transforms of integer order for propagating
      optical wave fields.
AB  - The method originally proposed by Yu et al. [Opt. Lett. 23, 409 (1998)] for
      evaluating the zero-order Hankel transform is generalized to high-order Hankel
      transforms. Since the method preserves the discrete form of the Parseval theorem,
      it is particularly suitable for field propagation. A general algorithm for
      propagating an input field through axially symmetric systems using the
      generalized method is given. The advantages and the disadvantages of the method
      with respect to other typical methods are discussed.

PMID- 14725398
TI  - Polarization-sensitive speckle spectroscopy of scattering media beyond the
      diffusion limit.
AB  - A scattering-media-characterization method that uses partially coherent radiation
      and polarization discrimination of multiply scattered light is described. The
      method is based on an analysis of the dependence of speckle contrast on the
      coherence length of the probe light. Polarization discrimination of detected
      speckles makes it possible to select scattered-light components that propagate in
      the probed medium at different distances. A theoretical analysis of the
      polarization-dependent speckle contrast as influenced by the probe-light
      coherence and parameters of the probed medium is presented. Experimental results
      obtained with various nondiffuse scattering samples are presented.

PMID- 14725399
TI  - Single scattering by a small volume element.
AB  - Starting from first principles, we present a detailed analysis of the concept of
      single scattering of light by a small volume element filled with sparsely and
      randomly positioned particles. We first derive the formulas of the far-field
      single-scattering approximation, which treats the volume element as a single
      scatterer, and discuss its range of applicability, using for illustration exact T
      matrix results for randomly oriented two-sphere clusters. Our second approach is
      to treat the volume element as a small cloud of particles and apply the so-called
      first-order-scattering approximation. We demonstrate that although the two
      approaches are based on somewhat different sets of assumptions, they give
      essentially the same result for the electromagnetic response of a sufficiently
      distant polarization-sensitive detector.

PMID- 14725400
TI  - Concept of the equiphase sphere for light scattering by nonspherical dielectric
      particles.
AB  - We introduce the concept of the equiphase sphere for light scattering by
      nonspherical dielectric particles. This concept facilitates the derivation of a
      simple analytical expression for the total scattering cross section of such
      particles. We tested this concept for spheroidal particles and obtained a bound
      on the minor-to-major axis ratio for the valid application of this technique. We
      show that this technique yields results that agree well with the rigorous
      numerical solution of Maxwell's equations obtained with the finite-difference
      time-domain method. The new technique has the potential to be extended to the
      study of light scattering by arbitrarily shaped convex dielectric particles.

PMID- 14725401
TI  - Corneal asphericity after refractive surgery when the Munnerlyn formula is
      applied.
AB  - We deduce a mathematical equation for corneal asphericity after refractive
      surgery when the Munnerlyn formula is used. For this, an analytical least-squares
      procedure is used. The equation explains the discrepancies found by different
      authors when the Munnerlyn formula or its paraxial approximation is used.
      Equations for corneal asphericity deduced here may be of clinical relevance, for
      example, in studying quantitatively the role of different factors (decentration,
      type of laser, optical role of the flap, wound healing, biomechanical effects,
      technical procedures) during corneal ablation.

PMID- 14725402
TI  - Radiation characteristics of a high-emissivity cylindrical-spherical cavity with
      obscuration.
AB  - We have calculated, to first order, the apparent emissivity of the bounding
      diffuse surfaces of a high-emissivity cylindrical-spherical cavity enclosure. Our
      calculations indicate that to achieve emissivities close to a perfectly absorbing
      blackbody cavity along the bounding surfaces of the spherical enclosure, the
      radius of the sphere must be equal to or greater than a factor of 4 times the
      cylinder radius R(S) > or = 4R(C). Furthermore, to achieve emissivities
      approaching a blackbody cavity along the lower bounding surfaces of the
      cylindrical enclosure, the length of the cylinder must be a factor of 4 times
      greater than the radius of the cylinder L > or = 4R(C). In addition, we present
      the mathematical framework necessary to calculate radiant transfer within a
      cavity enclosure that contains obscuration. These results can be applied to the
      design of high-emissivity blackbody calibration cavities and to the reduction of
      stray light in terrestrial and spaceborne optical systems.

PMID- 14725403
TI  - Analysis of characteristics of bent rib waveguides.
AB  - With a perfectly matched layer boundary treatment, a semivectorial finite
      difference method is used to calculate the eigenmodes of a single-mode (SM) or
      multimode (MM) bent rib waveguide. A detailed analysis is given for the
      dependence of the bending losses (including the pure bending loss and the
      transition loss) on geometrical parameters of the bent rib waveguide such as the
      rib width, the rib height, and the bending radius. The characteristics of the
      higher-order modes are analyzed. It is shown that the bending loss of the
      fundamental mode can be reduced effectively by increasing the width and height of
      the rib. For an integrated device, undesired effects due to the higher-order
      modes of a MM bent waveguide can be removed by appropriate choice of the
      geometrical parameters. An appropriately designed MM bent waveguide is used to
      reduce effectively the bending loss of the fundamental mode, and a low-loss SM
      propagation in a MM bent waveguide is realized when the bending losses of the
      higher-order modes are large enough.

PMID- 14725404
TI  - Perfect lenses made with left-handed materials: Alice's mirror?
AB  - In a recent paper, Pendry [Phys. Rev. Lett. 86, 3966 (2000)] mentioned the
      possibility of making perfect lenses by using a slab of left-handed material with
      relative permeability and permittivity equal to -1, a property first stated by
      Veselago [Sov. Phys. Usp. 10, 509 (1968)]. Pendry gave a demonstration of the
      vital effect of the evanescent waves in this process, arguing that these waves
      are amplified inside the slab. We present first a very simple theoretical
      demonstration that a homogeneous material with both relative permittivity and
      permeability equal to -1 cannot exist, even for a unique frequency. This
      demonstration shows that the perfect lens proposed by Pendry can be interpreted
      as a means to move in real space the virtual perfect image of a point source
      given by a plane mirror. We show that, owing to evanescent waves, the concept of
      effective medium for heterogeneous materials is questionable, even when the
      wavelength of the incident light is much larger than the size of the
      heterogeneities. The effect of heterogeneities is compared with that of
      absorption. We conclude that a material able to focus the light more efficiently
      than the current devices (but not perfectly) could exist.

PMID- 14725405
TI  - Application of the Jones calculus for a modulated double-refracted light beam
      propagating in a homogeneous and nondepolarizing electro-optic uniaxial crystal.
AB  - The Jones matrix calculus is applied to an electro-optic crystal with uniaxial
      symmetry when the light beam is incident nearly normally on the crystal face. The
      approach allows one to treat refracted waves and rays that diverge in the crystal
      and are modulated by an external low-frequency field. The effect of partial
      interference of overlapping refracted beams is allowed for and calculated for the
      case of uniform intensity of the beam over its cross section. The method is
      employed to analyze optical systems containing an imprecisely cut and aligned
      electro-optic crystal plate.

PMID- 14725406
TI  - Spectral changes and spectral switches of partially coherent beams focused by an
      aperture lens.
AB  - Starting from the propagation law of partially coherent polychromatic light in
      the space-frequency domain, detailed numerical results and physical analysis are
      given to elucidate spectral changes and spectral switches at the geometrical
      focal plane of Gaussian Schell-model beams focused by an aperture lens. It is
      found that, in contrast to the aperture-induced spectral anomalies of spatially
      fully coherent polychromatic light, for partially coherent polychromatic light
      aperture diffraction plays an important role in spectral switching, but the
      truncation parameter, spectral correlation, and bandwidth all affect its spectral
      behavior.

PMID- 14725407
TI  - Measurements of radiation characteristics of fused quartz containing bubbles.
AB  - We report experimental measurement of radiation characteristics of fused quartz
      containing bubbles over the spectral region from 1.67 to 3.5 microm. The
      radiation characteristics were retrieved by an inverse method that minimizes the
      quadratic difference between the measured and the calculated spectral
      bidirectional transmittance and reflectance for different sample thicknesses. The
      theoretical spectral transmittances and reflectances were computed by solving the
      one-dimensional radiative transfer equation by the discrete-ordinates method for
      a nonemitting, homogeneous, and scattering medium. The results of the inversion
      were shown to be independent of the sample thickness for samples thicker than 3
      mm and clearly demonstrate that bubbles have an effect on the radiation
      characteristics of fused quartz.

PMID- 14725408
TI  - Palliative care for children.

PMID- 14725409
TI  - Case fatality proportions and predictive factors for mortality among children
      hospitalized with severe pneumonia in a rural developing country setting.
AB  - Few large studies have evaluated risk factors for mortality among children
      hospitalized for pneumonia and this may contribute to suboptimal case management
      efficiency. To identify useful screening criteria for mortality among children
      hospitalized for pneumonia in a developing country setting, we conducted a
      population-based hospital cohort study among children less than 2 years of age
      admitted for pneumonia during 1999-2001 at one of three major hospitals on Lombok
      Island, Indonesia. Of 4351 children admitted for pneumonia, 12 per cent died
      before discharge. Case fatality proportions were seasonal, with peaks occurring
      immediately after peaks in the proportion of cases positive for respiratory
      syncytial virus. Children with an oxygen saturation < or = 85 per cent or age
      younger than 4 months were 5.6 times more likely to die than children with none
      of these predictive factors (95 per cent CI, 4.5-7.1); 83 per cent of children
      who died had one of these two risk factors. For children < 4 months old,
      mortality increased at an oxygen saturation < 88 per cent compared with < 80 per
      cent for older children. Laboratory, physical examination, and radiological
      findings were not associated with or did not contribute substantially to
      mortality prediction. Among children hospitalized for pneumonia, age less than 4
      months and hypoxia were identified with those at high risk of death. Age
      influences cut-off levels for hypoxia.

PMID- 14725410
TI  - Immunogenicity and safety of two doses of a paediatric hepatitis A vaccine in
      thai children: comparison of three vaccination schedules.
AB  - As fewer children in Thailand are exposed to hepatitis A virus (HAV) and so do
      not have seroprotective anti-HAV antibodies, they are becoming an important
      source of HAV transmission. A flexible HAV vaccination schedule would facilitate
      incorporation of the vaccine into existing immunization programmes, and we
      compared the immunogenicity and safety of three HAV immunization schedules. An
      open, randomized, clinical trial was carried out in which healthy children were
      given a primary dose of the inactivated hepatitis A vaccine, Avaxim 80
      paediatric, with a booster dose 6, 12 or 18 months later. Anti-HAV geometric mean
      concentrations (GMC), seroconversion rates, and GMC ratios (GMCR) of the three
      schedules were compared and reactogenicity was evaluated. Seroconversion rates
      were above 98 per cent (per group) up to the booster. The three schedules were
      equivalent in terms of GMCRs, each eliciting a large booster effect. Local
      reactions were reported for fewer than 9 per cent of each group after dose one
      and less frequently after the booster dose. Injection site pain, gastrointestinal
      tract disorders and fever were the most commonly reported adverse events. No
      vaccine-related serious adverse events were reported. It was concluded that the
      hepatitis A vaccine, Avaxim 80 paediatric, is safe and immunogenic when given as
      a two-dose schedule to healthy seronegative children aged 5-10 years, with the
      second dose given at either 6, 12 or 18 months after the first.

PMID- 14725411
TI  - A randomized controlled study of the impact of dietary zinc supplementation in
      the management of children with protein-energy malnutrition in Lesotho. I:
      Mortality and morbidity.
AB  - Protein-energy malnutrition (PEM) remains one of the common causes of morbidity
      and mortality among children throughout the world. The supplementation of 10 mg
      elemental zinc, as zinc sulphate, was evaluated in the management of PEM in a
      randomized, controlled double-blind clinical trial in 300 children, aged 6-60
      months (zinc, n = 150; control, n = 150) admitted to the Queen Elizabeth II
      Hospital, Maseru, Lesotho. Supplementation and follow-up were done for 3 months
      post-discharge from the hospital. Mortality during hospitalization was
      significantly lower in the zinc supplemented group (4.7 per cent), compared with
      16.7 per cent in the control group. The prevalence of morbidity was significantly
      higher in the control group at 1, 2, and 3 month's follow-up. In the zinc
      supplemented group 58 per cent of the children were above the 80th percentile of
      expected weight-for-age 3 months after discharge, compared with 27.6 per cent in
      the control group. Dietary zinc supplementation resulted in a significant
      reduction in diarrhoeal disease, respiratory morbidity, and episodes of clinical
      anaemia, skin infections, and fever as well as vomiting in children with PEM.
      These findings suggest that interventions to improve zinc intake in their
      management may be of benefit to Basotho children in Lesotho with PEM.

PMID- 14725412
TI  - A randomized controlled study of the impact of dietary zinc supplementation in
      the management of children with protein-energy malnutrition in Lesotho. II:
      Special investigations.
AB  - Protein-energy malnutrition (PEM) remains one of the common causes of morbidity
      and mortality among children throughout the world. The supplementation of 10 mg
      elemental zinc, as zinc sulphate, was evaluated in the management of PEM in a
      randomized, controlled, double-blind clinical trial in 300 children, aged 6-60
      months (zinc, n = 150; control, n = 150) admitted to the Queen Elizabeth II
      Hospital, Maseru, Lesotho. Supplementation and follow-up were done for 3 months
      post-discharge from the hospital. Both the supplemented and the control groups
      presented with biochemically determined zinc deficiency on presentation. Despite
      supplementation the treated group only began to show evidence of biochemical
      increase in serum zinc at 60 days post-discharge from hospital. This may
      represent the period of replacement of the total body zinc. Zinc deficiency was
      more severe in those children in the control group that died after admission to
      hospital than those that survived, suggesting that low serum levels in children
      with PEM are associated with a poor prognosis. Zinc did not emerge as a
      predicator of poor prognosis in the supplemented group as very few children died
      in this group. The supplemented group also made significant gains as far as
      albumin levels were concerned, which probably reflects rehabilitation of their
      malnutrition. The associated improvement in haematological parameters has not
      been described before and may be secondary to the decreased burden of disease in
      the supplemented group. These findings suggest that not only were significant
      benefits of zinc supplementation shown for morbidity in mortality of children in
      Lesotho with PEM, but these trends were also demonstrated on biochemical
      profiles.

PMID- 14725413
TI  - Kawasaki disease in Oman--a clinical study.
AB  - A total of 39 patients were diagnosed to have Kawasaki disease by the standard
      diagnostic criteria, at The Royal Hospital, Muscat, Oman, during the period
      January 1995 to August 2002. A retrospective analysis of the case records of the
      patients with the diagnosis of Kawasaki disease was done. The results of the
      clinical features and the laboratory manifestations of the patients, who are from
      the Middle East region, are presented. The peak age at presentation was 6-30
      months, mean 29 months. Peak months of the occurrence of the disease were March
      and October. Oral lesions were found in all cases. The mean duration of hospital
      stay for these patients was 8.5 days, range 2-21 days. The total duration of
      fever ranged from 6 to 21 days, with a mean value of 9.4 days. An elevated
      erythrocytic sedimentation rate (ESR; 91.7 per cent) and a raised C-reactive
      protein (C-RP; 92.3 per cent) were the most significant laboratory findings.
      Echocardiographic abnormalities were found in 25 per cent of cases, the incidence
      of coronary artery involvement (dilatation with or without stenosis) being 12.5
      per cent. High dose intravenous immunoglobulin (2 g/kg over a 12-h period) plus
      aspirin therapy was found to be safe and effective in patients with Kawasaki
      disease.

PMID- 14725414
TI  - Our experience with fulminant hepatic failure in Turkish children: etiology and
      outcome.
AB  - Fulminant hepatic failure is a rare and devastating event during childhood. The
      etiology of liver failure is reported to change according to age and geographical
      location. We aimed to investigate, retrospectively, causes and outcome of
      fulminant hepatic failure in Turkish children. Thirty-four children with
      fulminant hepatic failure were analysed by means of etiology and outcome.
      Etiological factor, clinical presentation, encephalopathy stage and biochemical
      parameters were correlated with outcome. Acute viral hepatitis was detected in 12
      cases (35.2 per cent) and hepatitis A was the most commonly detected cause among
      cases with fulminant hepatic failure (n = 9, 26.4 per cent). Hepatitis B and non
      A-E infection were diagnosed in two (5.8 per cent) and one (2.9 per cent) cases,
      respectively. Wilson's disease was defined in four patients (12.5 per cent). Budd
      Chiari syndrome (2.9 per cent), autoimmune hepatitis (2.9 per cent) and mushroom
      poisoning (2.9 per cent) were other detected causes of fulminant hepatic failure
      in this group. No viral, metabolic, toxic or anatomic reason could be detected in
      the remaining 15 (44.1 per cent) patients and they were evaluated as cryptogenic.
      Mortality was 67.6 per cent (23 cases). Encephalopathy grade, total and indirect
      bilirubin levels were found to be significantly higher in patients who died (p =
      0.004, p = 0.03, p = 0.04). Seven patients could have been transplanted (two
      cadavaric, five living related) and the mortality of this group was 28.5 per cent
      (n = 2). It was concluded that fulminant hepatitis A virus (HAV) infection is the
      most common detectable cause of fulminant hepatic failure in Turkish children.

PMID- 14725415
TI  - Seroepidemiology of hepatitis B and delta virus infections in Bangladesh.
AB  - Hepatitis B virus (HBV) infection is one of the most prevalent public health
      problems worldwide, and causes 1 million deaths annually. In Bangladesh,
      information about prevalence of HBV infection is scarce, and there is no
      available data on HDV infection. We determined rates of HBsAg and anti-HBc
      seropositivity in asymptomatic, healthy children (n = 181) and adults (n = 354)
      presenting to referral facilities in Dhaka, Bangladesh, and tested a separate
      group of HBsAg-positive patients (n = 180) for prevalence of HDV. Testing of
      serum was also performed for signs of liver disease. Overall, seropositivity of
      HBsAg and anti-HBc in studied subjects was 3 per cent (16/534) and 21.1 per cent
      (113/534), respectively. Prevalence of HBsAg was highest in the 5- to 9-year-old
      (8.5 per cent, 7/82) and 10- to 14-year-old (5.9 per cent, 2/34) age groups.
      Unlike HBsAg, prevalence of anti-HBc was lower in children (14.9 per cent in
      those below the age of 15) than adults (24.4 per cent in those aged 20-34 years)
      (p < 0.05). Most HBsAg-positive individuals were symptomatic (n = 125, 69.4 per
      cent). A high rate (24.4 per cent, 44/180) of simultaneous infection with HDV was
      observed among HBsAg-positive subjects, with higher rates in older individuals.
      Anti-HDV seropositivity rate was similar among asymptomatic (21.8 per cent,
      12/55) and symptomatic (25.6 per cent, 32/125) HBsAg carriers. Our data suggest
      that Bangladesh is of moderate endemicity for HBV infection, and has relatively
      high rates of co-infection with HDV. Control HBV and HDV infection in Bangladesh
      may be best achieved by targeting preschool children, which could fit readily
      within the existing EPI schedule.

PMID- 14725416
TI  - Treatment of chronic hepatitis B--a paediatric perspective.

PMID- 14725417
TI  - The validity of diagnostic criteria for streptococcal pharyngitis in Integrated
      Management of Childhood Illness (IMCI) guidelines.
AB  - The WHO's Integrated Management of Childhood Illness (IMCI) programme is being
      implemented in Turkey with an additional section relating to throat problems for
      our country's adaptation. The aim of this study is to evaluate the validity of
      this additional part and suggest new combinations for the diagnosis of
      streptococcal pharyngitis to improve the guidelines. Throat swabs were obtained
      from 245 children between 0 and 17 years of age with signs and symptoms of upper
      respiratory tract infections. Considering the throat culture based diagnosis as
      the gold standard, the validity of the symptoms alone and in combinations were
      calculated. The combination in Turkey's IMCI guideline was found to be 36.9 per
      cent sensitive and 68.3 per cent specific. Sensitivities of combinations
      including at least two of the following three symptoms, namely sore throat,
      pharyngeal erythema, and pharyngeal exudates or sore throat, pharyngeal erythema,
      and fever, were 76.9 and 87.7 per cent, respectively. Specificities of the same
      combinations were 49.4 and 30.6 per cent. We concluded that new combinations with
      a higher sensitivity may be considered as a criterion for antibiotic treatment.

PMID- 14725418
TI  - Risk of seizure recurrence following a first unprovoked seizure in children.
AB  - The aim of the study was to determine seizure recurrence rate and risk factors of
      a first unprovoked seizure in children. Ninety-one children aged 2 months-15
      years who had a first unprovoked seizure were enrolled and followed-up. History
      and physical examination were undertaken. The results were displayed as a Kaplan
      Meier survival curve. Multivariate analysis was performed with Cox proportional
      hazards model. The cumulative probability of recurrence rate was 68 per cent and
      incidence density was 6.85 per 100 person-months. The cumulative risk of
      recurrence was 50 per cent at 4 months and 66 per cent at 12 months. No risk of
      seizure recurrence was found in this study.

PMID- 14725419
TI  - Intrauterine growth curves for Turkish infants born between 25 and 42 weeks of
      gestation.
AB  - Intrauterine growth curves should be specific to each population and are needed
      for the Turkish population. An analysis of birthweight, crown-heel length, and
      head circumference in newborns between 25 and 42 weeks of gestational age was
      made. A total of 2481 babies were evaluated. Mean, standard deviation, and
      percentile values were calculated for each gestational age and smoothed curves
      were obtained for each parameter. In our country, the use of these new curves is
      more appropriate than those obtained in other countries.

PMID- 14725420
TI  - Natural history of hepatitis C virus among apparently normal schoolchildren:
      follow-up after 7 years.

PMID- 14725421
TI  - Quality of dental implants.
AB  - BACKGROUND: Clinicians need quality research data to decide which dental implant
      should be selected for patient treatment. AIM(S)/OBJECTIVE(S): To present the
      scientific evidence for claims of relationship between characteristics of dental
      implants and clinical performance. STUDY DESIGN: Systematic search of promotional
      material and Internet sites to find claims of implant superiority related to
      specific characteristics of the implant, and of the dental research literature to
      find scientific support for the claims. MAIN OUTCOME MEASURES: Critical appraisal
      of the research documentation to establish the scientific external and internal
      validity as a basis for the likelihood of reported treatment outcomes as a
      function of implant characteristics. RESULTS: More than 220 implant brands have
      been identified, produced by about 80 manufacturers. The implants are made from
      different materials, undergo different surface treatments and come in different
      shapes, lengths, widths and forms. The dentist can in theory choose among more
      than 2,000 implants in a given patient treatment situation. Implants made from
      titanium and titanium alloys appear to perform well clinically in properly
      surgically prepared bone, regardless of small variations of shapes and forms.
      Various surface treatments are currently being developed to improve the capacity
      of a more rapid anchorage of the implant into bone. A substantial number of
      claims made by different manufacturers on alleged superiority due to design
      characteristics are not based on sound and long-term clinical scientific
      research. Implants are, in some parts of the world, manufactured and sold with no
      demonstration of adherence to any international standards. CONCLUSIONS: The
      scientific literature does not provide any clear directives to claims of alleged
      benefits of specific morphological characteristics of dental implants.

PMID- 14725422
TI  - Changes to legislation governing slaughter.

PMID- 14725423
TI  - Frequencies of prion protein (PrP) genotypes and distribution of ages in 15
      scrapie-affected flocks in Great Britain.
AB  - The frequencies of prion protein (PrP) genotypes were investigated in 15 scrapie
      affected flocks in Great Britain. The flocks were heterogeneous in the
      frequencies of different genotypes and alleles, and in their age distributions.
      The median flock frequency of animals with VRQ-containing genotypes was 21 per
      cent (range 2 to 82 per cent, mean 25 per cent). The VRQ-containing and other non
      ARR genotypes made up 11 to 82 per cent of a flock (median 46 per cent, mean 48
      per cent). In comparison with data from the general population the scrapie
      affected population had a lower frequency of the ARR/ARR genotype, and so of the
      ARR allele, and had a higher frequency of VRQ/non-ARR heterozygote genotypes, and
      thus of the VRQ allele.

PMID- 14725424
TI  - Helminths isolated from the digestive tract of diurnal raptors in Catalonia,
      Spain.
AB  - The prevalence of parasitic helminths in the digestive tract of 119 diurnal
      raptors (Falconiformes), which had died in a wildlife rehabilitation centre in
      Catalonia, was studied. The birds belonged to 13 species, with 100 of them (84
      per cent) being kestrels (Falco tinnunculus), buzzards (Buteo buteo),
      sparrowhawks (Accipiter nisus) and goshawks (Accipiter gentilis). Ninety-five of
      the birds (79.8 per cent) were infected with helminths. Nematodes were the most
      frequently found helminth (75.6 per cent), followed by trematodes, cestodes and
      ancanthocephalans. All the buzzards and sparrowhawks and 92 per cent of the
      goshawks were infected, but only 59 per cent of the kestrels were infected.

PMID- 14725425
TI  - Dissemination of central nervous system tissue during the slaughter of cattle in
      three Irish abattoirs.
AB  - Sponge samples were taken from the carcases, meat, personnel and surfaces
      involved in stunning, slaughter and dressing/boning activities at three
      abattoirs, and from retail beef products. The samples were examined for the
      presence of central nervous system (CNS)-specific proteins (syntaxin 1B and/or
      glial fibrillary acidic protein (GFAP), as indicators of contamination with CNS
      tissue. Syntaxin 1B and GFAP were detected in many of the sponge samples taken
      along the slaughter line and in the chill rooms of all three abattoirs; GFAP was
      also detected in one sample of longissimus muscle (striploin) taken in the boning
      hall of one of the abattoirs but not in the other two abattoirs or in retail
      meats.

PMID- 14725427
TI  - Use of an injectable, sustained-release formulation of moxidectin to prevent
      canine subcutaneous dirofilariosis.

PMID- 14725428
TI  - Delivery of a Holstein-Friesian calf with multiple skeletal abnormalities.

PMID- 14725426
TI  - Detection of porcine reproductive and respiratory syndrome virus in pigs with low
      positive or negative ELISA s/p ratios.

PMID- 14725429
TI  - In the still of the night.
AB  - With medical general practitioners soon being able to buy themselves out of the
      requirement to provide overnight cover for their patients, for how much longer
      will the veterinary profession be able to sustain its 24-hour commitment? Here,
      Professor Bob Michell argues that it is time for the profession to rethink how it
      provides out-of-hours services--and, with the RCVS about to review the situation,
      concludes that something will have to change.

PMID- 14725430
TI  - Rimadyl Palatable Tablets.

PMID- 14725431
TI  - BVA/KC Hip and Elbow Dysplasia Schemes.

PMID- 14725432
TI  - Cracked pads/corny feet in Bedlington terriers.

PMID- 14725433
TI  - Congenital necrotizing encephalopathy in lambs.

PMID- 14725434
TI  - Estimation of pKa using quantum topological molecular similarity descriptors:
      application to carboxylic acids, anilines and phenols.
AB  - The current availability of cheap computer power enables the construction of
      QSARs from modern ab initio quantum chemical data. Multivariate models for three
      classes of compounds are developed by means of the quantum topological molecular
      similarity (QTMS) tool, which incorporates descriptors originating from the
      "Atoms in Molecules" (AIM) theory. Correlations obtained outperform the Hammett
      and other traditional parameters. The advantage of QTMS over semiempirical and
      empirical descriptors is demonstrated by the following r(2)/q(2) values:
      0.920/0.891 (acids), 0.974/0.953 (anilines), and 0.952/0.884 (phenols).

PMID- 14725435
TI  - Lithium hexamethyldisilazide-mediated ketone enolization: the influence of
      hindered dialkyl ethers and isostructural dialkylamines on reaction rates and
      mechanisms.
AB  - Mechanistic studies of the enolization of 2-methylcyclohexanone mediated by
      lithium hexamethyldisilazide (LiHMDS; TMS(2)NLi) solvated by hindered dialkyl
      ethers (ROR') are described. Rate studies using in situ IR spectroscopy show that
      enolizations in the presence of i-Pr(2)O, 2,2,5,5-tetramethyltetrahydrofuran, and
      cineole proceed via dimer-based transition structures
      [(TMS(2)NLi)(2)(ROR')(ketone)]. Comparing the relative solvation energies and the
      corresponding solvent-dependent activation energies shows that the highly
      substituted ethers accelerate the enolizations by sterically destabilizing the
      reactants and stabilizing the transition structures. Comparisons of hindered
      dialkyl ethers with their isostructural dialkylamines reveal that the
      considerably higher rates elicited by the amines derive from an analogous
      relative destabilization of the reactants and relative stabilization of the
      transition structures.

PMID- 14725436
TI  - Synthesis of a non-heme template for attaching four peptides: an approach to
      artificial iron(II)-containing peroxidases.
AB  - We are developing all-synthetic model cofactor-protein complexes in order to
      define the parameters controlling non-natural cofactor activity. The long-term
      objective is to establish the theoretical and practical basis for designing novel
      enzymes. A non-heme pentadentate ligand (N4Py) is being developed as a template
      for the site-specific attachment of a designed four-helix bundle. Previously, we
      attached two unprotected peptides via CH(2)Cl handles to N4Py. In the presence of
      hydrogen peroxide, the iron(II) complex of this ligand (2a) generates an
      Fe(III)OOH intermediate (3a) that can oxidize a wide variety of organic
      compounds. Here, we describe the synthesis of 27, a N4Py derivative in which four
      three-carbon spacers have been introduced, and show that four copies of an
      unprotected, single-cysteine peptide can be coupled via a thioether linkage to
      the ligand. In addition, a divergent synthesis route to tetrabromide ligand 1b
      has also been developed, providing the opportunity to prepare alternative
      pentadentate ligands efficiently by four cross-coupling reactions on a single
      molecule. Also, two of the four bromides of 1b can be selectively addressed by
      magnesium-bromide exchange.

PMID- 14725437
TI  - Electron-transfer-induced substitution of alkylated C60 chlorides with proton
      sponge.
AB  - A series of alkylated C(60) chlorides 1,4-RC(60)Cl (1) were found to undergo
      nucleophilic substitution with 1,8-bis(dimethylamino)naphthalene (2), affording
      1,4-RC(60)Ar [3, Ar = 4,5-bis(dimethylamino)-1-naphthyl] in good yields. An
      S(RN)1 mechanism, initiated by a single-electron transfer from 2 to 1, is
      proposed on the basis of the enhanced rates compared with the rate of the S(N)1
      reaction of 1 with anisole. The involvement of free radicals in the reaction is
      supported by the formation of a small amount of dimer RC(60)-C(60)R (4) as a
      byproduct. The enhanced ability of C(60) chlorides 1 to accept an electron,
      attributable to the inductive effect of the directly attached chlorine atom, was
      demonstrated by its reduction potential and calculated LUMO energy.

PMID- 14725438
TI  - Zipper-featured delta-peptide foldamers driven by donor--acceptor interaction.
      Design, synthesis, and characterization.
AB  - Donor-acceptor interaction between electron-rich 1,5-dioxynaphthalene (DAN) and
      electron-deficient pyromellitic diimide (PDI) has been utilized to induce the
      formation of a new kind of zipper-featured delta-peptide foldamers. Seven l
      ornithine-based delta-peptides 1a-g, in which one to three DNA and PDI units are
      incorporated to the two ends of the peptide backbones, respectively, have been
      designed and prepared by the standard liquid-phase synthetic method. (1)H NMR, UV
      vis, and fluorescent quenching studies reveal that all the delta-peptides adopt
      folding conformations in nonpolar chloroform and polar DMF as a result of
      intramolecular donor-acceptor interaction between the DAN and PDI units. The
      folding states become more compact for the peptide skeletons possessing more
      donor-acceptor interacting sites. Variable-temperature UV-vis experiments
      indicate that, although the folding is a dynamic process, the folding state can
      remain even at 150 degrees C in DMF. Circular dichroism (CD) investigations
      reveal that the new generation of delta-peptides have similar folding patterns. A
      zipper-featured folding motif has been proposed for the new generation of delta
      peptide foldamers. Molecular modeling has generated two most stable folding
      states for the longest delta-peptide 1g, with an energy difference of 26.80
      kcal/mol.

PMID- 14725439
TI  - Novel chimeric scaffolds to extend the exploration of receptor space: hybrid beta
      D-glucose-benzoheterodiazepine structures for broad screening. Effect of amide
      alkylation on the course of cyclization reactions.
AB  - New molecular platforms which are hybrids of two scaffolds-namely, beta-d-glucose
      and benzodiazepine, each able to bind several proteins-were designed, synthesized
      and functionalized to serve as probes for broad biological screening. Herein, we
      describe the syntheses and chemical properties of these novel chimeric scaffolds.
      Attempted cyclization of the functionalized analogues (-)-96 and (-)-97 afforded
      the corresponding dimers (-)-98 and (-)-99, respectively, under a variety of
      reaction conditions, even at concentrations of only 0.001 N. Consideration of
      factors affecting the conformation of amide bonds and their effects on
      cyclization reactions led us to alkylate the amide bond. As expected, the
      cyclization of the N-methyl derivative (-)-110 afforded exclusively the
      unimolecular cyclization product (+)-111. These compounds are only now undergoing
      broad screening and represent therefore at present a "prospecting library."

PMID- 14725440
TI  - General and efficient insertion of carbons carrying benzotriazole.
AB  - Anions formed from the lithiation of 1-(1-benzotriazolylalkyl)benzotriazoles (1,
      6) and 1-(1-methylthioalkyl)benzotriazoles (10 and 10a) with n-BuLi underwent
      additions to cyclic and acyclic ketones giving intermediates 3a-f, 7b-f, and 11b
      d, respectively, in excellent yields. Thermal rearrangements of intermediates
      3a,b,d-f and 7b-d,f in the presence of zinc bromide provided one-carbon chain
      extended or ring-expanded alpha-benzotriazolyl ketones 4a,b,d-f and 8b-d,f in
      moderate yields with excellent regioselectivity. By contrast, intermediates 11b-d
      on treatment with zinc bromide loose a molecule of benzotriazole followed by
      intramolecular cyclization of the resulting intermediates 12b-d to provide the
      2,3- and 1,2,3-substituted indenes 13b-d in good yields.

PMID- 14725441
TI  - Efficient synthesis of polysubstituted acylguanidines and guanylureas.
AB  - (Benzotriazol-1-yl)carboximidamides were applied for the preparation of
      polysubstituted acylguanidines and guanylureas. The reaction sequence utilized
      mild conditions and gave high yields for final compounds and intermediates. The
      protocol developed allows for variation of the substituents at all positions of
      the products.

PMID- 14725442
TI  - Synthesis of chemically stabilized phosmidosine analogues and the structure-
      activity relationship of phosmidosine.
AB  - Phosmidosine is known to have potent antitumor activity and the unique property
      of stopping cell growth at the G(1) phase in the cell cycle. However, this
      natural product having N-prolylphosphoramidate and O-methyl ester linkages on the
      5'-phosphoryl residue is unstable under basic conditions and even during the
      chemical synthesis due to its inherent methyl transfer activity. To find stable
      derivatives of phosmidosine, a variety of phosmidosine analogues 1a-d replaced by
      longer alkyl groups in place of the methyl group on the phosphoramidate linkage
      were synthesized by reaction of alkyl N-(N-tritylprolyl)phosphorodiamidite
      derivatives 7a-d with an 8-oxoadenosine derivative 4 protected with acid-labile
      protecting groups. Consequently, the O-ethyl ester derivative 1b was found to be
      sufficiently stable in aqueous solution. When the prolyl group was replaced by
      other aminoacyl moieties, the reaction of N-tritylaminoacylamide derivatives 25a
      d with an appropriately protected 8-oxoadenosine 5'-(ethyl phosphoramidite)
      derivative 9 gave better results than the above coupling reaction. A
      phosphoramidothioate derivative 17 and several simple compounds such as 11, 13,
      and 15 lacking partial structures of phosmidosine were also synthesized. The
      antitumor activities of these modified analogues were extensively studied to
      clarify the structure-activity relationship of phosmidosine. As a result, the two
      diastereoisomers of longer alkyl-containing phosmidosine analogues both proved to
      have similar antitumor activities. Replacement of l-proline with other l-amino
      acids or d-proline resulted in considerable decrease of the antitumor activity.
      The non-nucleotidic materials 13 did not show any antitumor activity, but a
      simple core compound of 11 exhibited weak cytotoxicity. The phosphoramidothioate
      derivative 17 maintained essentially a similar antitumor activity, but the
      efficiency decreased slightly.

PMID- 14725443
TI  - A novel class of tunable zinc reagents (RXZnCH2Y) for efficient cyclopropanation
      of olefins.
AB  - A class of zinc reagents (RXZnCH(2)Y) generated with an appropriate organozinc is
      very effective for the cyclopropanation of olefins. The reactivity and
      selectivity of these reagents can be regulated by tuning the electronic and
      steric nature of the RX group on Zn. A reasonable level of enantioselectivity was
      obtained for the cyclopropanation of unfunctionalized olefins when a chiral
      (iodomethyl)zinc species was used, providing a valuable approach for the
      asymmetric cyclopropanation of unfunctionalized olefins.

PMID- 14725444
TI  - Facile preparation of beta-fluoro amines by the reaction of aziridines with
      potassium fluoride dihydrate in the presence of Bu4NHSO4.
AB  - Potassium fluoride combined with tetrabutylammonium bisulfate is an efficient
      reagent to convert a variety of aziridines derived from cyclic and acyclic
      alkenes to beta-fluoro amine derivatives in high yield.

PMID- 14725445
TI  - Kinetics and mechanisms of hydrolysis and aminolysis of thioxocephalosporins.
AB  - The effect of replacing the beta-lactam carbonyl oxygen in cephalosporins by
      sulfur on their reactivity has been investigated. The second-order rate constant
      for alkaline hydrolysis of the sulfur analogue is 2-fold less than that for the
      natural cephalosporin. The thioxo derivative of cephalexin, with an amino group
      in the C7 side chain, undergoes beta-lactam ring opening with intramolecular
      aminolysis by a reaction similar to that for cephalexin itself. However, the rate
      of intramolecular aminolysis for the S-analogue is 3 orders of magnitude greater
      than that for cephalexin. Furthermore, unlike cephalexin, intramolecular
      aminolysis in the S-analogue occurs up to pH 14 with no competitive hydrolysis.
      The rate of intermolecular aminolysis of natural cephalosporins is dominated by a
      second-order dependence on amine concentration, whereas that for
      thioxocephalosporins shows only a first-order term in amine. The Bronsted
      beta(nuc) for the aminolysis of thioxo-cephalosporin is +0.39, indicative of rate
      limiting formation of the tetrahedral intermediate with an early transition state
      with relatively little C-N bond formation.

PMID- 14725446
TI  - Conformational studies by dynamic NMR. 97. Structure, conformation,
      stereodynamics and enantioseparation of aryl substituted norbornanes.
AB  - The structure of a 1,7,7-triaryl norbornane (compound 3) has been determined by X
      ray diffraction and was found essentially equal to that predicted by molecular
      mechanics calculations. Restricted rotation of the aryl groups also has been
      observed by dynamic NMR spectroscopy in this compound and in a number of
      analogously substituted norbornanes. The aryl-norbornane bond rotation barriers
      were measured by line shape analysis of the (13)C NMR spectra obtained at
      temperatures lower than -100 degrees C and were found to cover the range 6.0 to
      7.9 kcal mol(-1). An exception was the rotation involving the o-anisyl group in
      compound 5, which occurs near ambient temperature since the corresponding barrier
      is much higher (14.4 kcal mol(-1)). In one case (compound 4) configurational
      enantiomers could be separated by chiral HPLC and the corresponding CD spectra
      recorded.

PMID- 14725447
TI  - Novel spirocyclic trichothecanes, spirotenuipesine A and B, isolated from
      entomopathogenic fungus, Paecilomyces tenuipes.
AB  - Entomopathogenic fungi forming fruiting bodies have been employed as tonics and
      antitussives from ancient times. Paecilomyces tenuipes, which is also called
      Isaria japonica, is a very popular entomopathogenic fungus and is often
      considered a health food in northeast Asian countries such as China, Korea, and
      Japan. We cultivated the fruiting bodies of Paecilomyces tenuipes. Among the
      large-scale cultivations, fruiting body grown in barley grain contained two novel
      spirocyclic trichothecane derivatives, spirotenuipesine A (1) and B (2), and
      known trichothecane mycotoxins. Compounds 1 and 2 showed potent activity in
      neurotrophic factor biosynthesis in glial cells. The isolation of these compounds
      indicated that P. tenuipes is a promising source for producing various
      biologically active substances including trichothecanes. It is noteworthy that
      trichothecane mycotoxins are present in Paecilomyces tenuipes, which is typically
      used in medicinal health food.

PMID- 14725448
TI  - MetAP-2 inhibitors based on the fumagillin structure. Side-chain modification and
      ring-substituted analogues.
AB  - The preparation of a series of new fumagillin-derived MetAP-2 inhibitors is
      described. The synthetic approach was designed so as to permit modification of
      the fumagillin backbone at sites inaccessible through semisynthesis or previously
      existing total syntheses. An Evans aldolization and a ring-closing metathesis
      allowed the preparation of a pivotal intermediate which could then be
      functionalized in various ways using already established or newly developed
      methodologies.

PMID- 14725449
TI  - Stereodifferentiation in the decay of triplets and biradicals involved in
      intramolecular hydrogen transfer from phenols or indoles to pi,pi aromatic
      ketones.
AB  - Laser flash photolysis studies on (R,S) and (S,S) diastereoisomers of the
      bichromophoric compounds 1-6 have been used to investigate the possible chiral
      discrimination in the quenching of triplet excited ketones, resulting in formal
      hydrogen abstraction. Deuterium isotopic effects show that triplet deactivation
      in these bichromophores is dominated by hydrogen atom transfer. A remarkable
      stereodifferentiation is found in the intramolecular quenching of the ketone
      triplets of 1-3 and 5 by the phenolic or indolic moieties, either in methanol or
      acetonitrile as solvents. This indicates the existence of specific structural
      requirements for hydrogen transfer. On the other hand, the lifetimes of the
      generated biradicals show large solvent dependence; solvation appears to slow
      their reversion to the starting ketone. The considerable stereodifferentiation
      observed for the biradical lifetimes suggests that the kinetics of biradical
      decay is faster when the approach of the two radical termini becomes easier.

PMID- 14725450
TI  - A computational investigation of the reactions of methylene, chlorocarbene, and
      dichlorocarbene with cyclopropane.
AB  - The reactions of CH(2), CHCl, and CCl(2) with cyclopropane, 1, have been examined
      computationally. In all cases the lowest energy reaction between the carbene and
      1 is predicted to be C-H insertion. In the reaction of CH(2) with 1, the
      transition state for C-C insertion leading to cyclobutane is 1.7 kcal/mol higher
      in enthalpy than the transition state for C-H insertion at the G3B3 level. A
      pathway higher in energy than C-H insertion in the reactions of CHCl and CCl(2)
      with 1 involves two-bond cleavages generating ethylene along with chloro and
      dichloroethylene, respectively.

PMID- 14725451
TI  - An efficient and highly stereocontrolled route to bulgecinine hydrochloride.
AB  - (-)-Bulgecinine is a nonproteinogenic amino acid component present in bulgecins
      A, B, and C, antibiotic glycopeptides derived from Pseudomonas acidophila and
      Pseudomonas mesoacidophila. In combination with beta-lactam antibiotics,
      bulgecins exihibit a unique synergistic antibacterial activity against various
      Gram-negative microorganisms. Utilizing d-serine as a chiral template and
      employing a highly regio- and stereoselective intramolecular amidomercuration
      oxidation protocol in the key pyrrolidine ring forming step, an efficient total
      synthetic route to enantiopure bulgecinine is reported herein.

PMID- 14725452
TI  - Ionic liquid as an efficient promoting medium for fixation of CO2: clean
      synthesis of alpha-methylene cyclic carbonates from CO2 and propargyl alcohols
      catalyzed by metal salts under mild conditions.
AB  - Reactions of propargylic alcohols with CO(2) in a [BMIm][PhSO(3)]/CuCl catalytic
      system to produce the corresponding alpha-methylene cyclic carbonates were
      conducted with high yields. Mild reaction conditions, enhanced rates, improved
      yields, and recyclable ionic liquid catalyst systems are the remarkable features
      exhibited in this process. Furthermore, the use of large amounts of tertiary
      amines as well as nitrogen-containing organic solvent as employed in previously
      studies was avoided.

PMID- 14725453
TI  - Rhodium complex-catalyzed cycloisomerization of allenenes: exo and endo
      cyclization depending on the auxiliary ligands.
AB  - In the presence of a catalytic amount of a rhodium(I) complex, allenenes undergo
      cycloisomerization reactions resulting in the selective formation of exo
      alkylidenecarbocycles and heterocycles. In the catalytic system of rhodium
      complexes with triaryl phosphites, cyclic 1,4- or 1,5-dienes are formed in good
      to excellent yields in the formal exo-cyclization mode via the metallacycle
      intermediate having an exo-alkylidene moiety. In this cycloisomerization, (E)-
      and (Z)-allenenes are transformed stereospecifically to the corresponding cyclic
      (E)- and (Z)-1,4-dienes, respectively. On the other hand, the reactions under
      carbon monoxide atmosphere exclusively afford seven-membered-ring products
      through an endo-mode cyclization. The unusual cyclization involves an allylic C-H
      activation process. The allenene bearing a silicon substituent at the olefinic
      terminus incorporates carbon monoxide to give the corresponding [2+2+1]
      cycloaddition product. This result apparently indicates that the catalysis of the
      rhodium complex is explained in terms of the oxidative cyclization of an allenene
      to furnish the key exo-alkylidene metallacycle intermediate at the first stage of
      the catalysis.

PMID- 14725454
TI  - Bicyclo[3.2.1]octane synthons from cyclopropenes: functionalization of
      cycloadducts by nucleophilic additions.
AB  - It has been known for several decades that a highly functionalized family of
      tetrahalobicyclo[3.2.1]octadienes are readily available through the cycloaddition
      of furan or cyclopentadiene with either tetrachloro- or tetrabromocyclopropene.
      However, the application of these highly functionalized building blocks in
      synthesis has remained relatively unexplored in relation to their better-known
      counterparts derived through oxyallyl cation additions. As a first step toward
      utilizing these highly versatile intermediates in synthesis, a study of the
      addition of various nucleophiles to the halogenated nucleus has been conducted.
      It has been found that these halogenated systems are amenable to a wide range of
      functionalizations in high yields and with good selectivities.

PMID- 14725455
TI  - Highly efficient aza-Baylis-Hillman reaction of N-tosylated imines with MVK,
      acrolein, and phenyl acrylate or alpha-naphthyl acrylate: Lewis base effects and
      a convenient method to synthesize alpha,beta-unsaturated beta-amino carbonyl
      compounds.
AB  - This paper describes several highly efficient aza-Baylis-Hillman reactions of N
      tosylated imines with MVK, acrolein, and phenyl acrylate or alpha-naphthyl
      acrylate in the presence of a Lewis base. In most cases, the reaction can be
      completed within 1 h using the appropriate Lewis base catalyst. An efficient
      method to synthesize beta-amino ketones, aldehydes and esters in high yields and
      short reaction time has been developed.

PMID- 14725456
TI  - Ring-opening reactions of MCPs with sulfonamides promoted by metal triflate Lewis
      acids.
AB  - The reaction of aromatic MCPs with sulfonamides catalyzed by Lewis acids affords
      the corresponding ring-opened homoallylic sulfonamides in good yields and the
      reaction of aliphatic MCPs with sulfonamides gives the corresponding pyrrolidine
      derivatives under the same conditions. Through deuterium-labeling experiments, we
      found that the reaction process is involved with the rearrangement of a
      cyclopropylcarbinyl cation and a nonclassic carbonium ion.

PMID- 14725457
TI  - Wagner-Meerwein skeletal rearrangement of 3-spiroannulated 6,8a-epoxy- and
      6,8a;7,8-diepoxyisoquinolines (3-aza-11-oxatricyclo[6.2.1.0(1,6)]undec-9-enes).
      Isolation and identification of 5-aza-2-oxatricyclo[6.2.1.0(3,9)]undec-3-enes.
AB  - The reactions of 3-acetyl-3-aza-11-oxatricyclo[6.2.1.0(1,6)]undec-9-ene and its
      9,10-epoxy derivative with bromine and Ac(2)O/BF(3).OEt(2) under different
      conditions were studied. Unusual products of Wagner-Meerwein rearrangement
      bearing the olefin fragment (5-aza-2-oxatricyclo[6.2.1.0(3,9)]undecen-3-enes)
      were isolated and characterized by X-ray analysis.

PMID- 14725458
TI  - Oxime carbapalladacycle covalently anchored to high surface area inorganic
      supports or polymers as heterogeneous green catalysts for the Suzuki reaction in
      water.
AB  - An oxime carbapalladacycle known as an extremely active homogeneous catalyst for
      the Suzuki coupling in water has been conveniently modified and anchored on high
      surface area SiO(2), MCM-41, and polystyrene-divinylbenzene and ethylenglycol
      dimethylacrylate polymers. The resulting solids were characterized by analytical
      and spectroscopic (UV-vis and IR) techniques and tested as catalysts for the
      reaction of 4-chloroacetophenone with phenylboronic acid in water, dioxane, and a
      mixture of both. Differences in activity depending on the support were
      remarkable, the palladium complex being more active for the reactions in water
      when supported on SiO(2) or MCM-41. The catalysts were truly heterogeneous (no
      leached palladium) and when anchored on SiO(2) were reused seven times without
      loosing activity. Palladium complex anchored in SiO(2) was also tested as Suzuki
      catalyst for a wide range of bromo-, chloro-, and even fluoroaromatics.

PMID- 14725459
TI  - Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An
      expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and
      bicyclo[2.2.2]octa-5,7-dien-2-ones.
AB  - The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13),
      bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a
      d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the
      first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl
      2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d
      to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were
      initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5
      diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence
      of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene
      equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the
      Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been
      carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of
      triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence
      of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired
      bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively,
      in good overall yields.

PMID- 14725460
TI  - Structure assignment, total synthesis, and evaluation of the phosphatase
      modulating activity of glucolipsin A.
AB  - The previously unknown stereostructure of glucolipsin A (1), a complex glycolipid
      endowed with glucokinase-activating properties, was unambiguously elucidated as
      (2R,2'R,3S,3'S) by comparison of its spectroscopic and analytical data with those
      of all conceivable C(2)-symmetric stereoisomers. This set of macrodiolides was
      prepared by a sequence comprising auxiliary guided aldol reactions, glycosidation
      of the resulting beta-hydroxy acid derivatives with trichloroacetimidate 7,
      followed by hydrolytic cleavage of the auxiliaries used. The hydroxy acids thus
      formed were subjected to a macrodilactonization reaction mediated by 2-chloro-1,3
      dimethylimidazolinium chloride (22) as the activating agent; this transformation
      is highly productive only in the presence of admixed potassium cations which
      likely serve as templates to preorganize two substrate molecules in a favorable
      head-to-tail arrangement. Glucolipsin and analogues were subjected to enzymatic
      assays that revealed that glycoconjugates of this type effectively inhibit the
      activity of the dual specific phosphatase Cdc25A with IC(50) values in the low
      micromolar range, while being hardly active against the tyrosine phosphatase
      PTP1B in vitro. This activity profile was compared to that of other glycolipids
      previously prepared in this laboratory, including cycloviracin B(1) (2),
      caloporoside (38), woodrosin I (39), sophorolipid lactone (40), and tricolorin G
      (41).

PMID- 14725461
TI  - Molybdenum-catalyzed stannylations as key steps in heterocyclic synthesis.
AB  - THF/carbonyl complexes of molybdenum and tungsten are suitable precursors for the
      synthesis of the corresponding monoisonitrile carbonyl complexes. Whereas
      complexes with electron-rich isonitriles are suitable for regioselective
      hydrostannations, complexes with electron-poor isonitriles are efficient
      catalysts for distannations, without reduction of aromatic halides. This allows
      for the synthesis of halogenated distannylated allyl ethers, which can be
      subjected to intramoleculare Stille couplings giving rise to heterocycles, which
      can be further modified at the remaining stannyl group.

PMID- 14725462
TI  - Preparation and characterization of new chiral nitronyl nitroxides bearing a
      stereogenic center in the imidazolyl framework.
AB  - A synthetic procedure for optically active and racemic alpha-nitronyl nitroxides
      (alpha-NNs) having a stereogenic center at the 4-position of the imidazolyl ring
      is described. This procedure consists of (1) the synthesis of a dissymmetric vic
      dinitro compound by Kornblum reaction, (2) the enantiomeric resolution of the
      racemate by a diastereomer method for obtaining the optically active sample, (3)
      the quick reduction of the optically active or racemic vic-dinitro compound to
      the bis(hydroxyamino) derivative with Al/Hg, (4) the solvent-free condensation of
      the bis(hydroxyamino) compound with an aldehyde to give the 1,3
      dihydroxyimidazolidine, and (5) the final oxidation of the alpha-NN precursor
      with aqueous NaIO(4). The absolute configuration of the optically active alpha
      NNs was assigned by correlating with the X-ray crystal structure of the (-)
      (1S,4R)-camphanic acid ester derivative of the optically active vic-dinitro
      compound. The molecular conformation of the optically active alpha-NNs was found
      to be folded both in solution and in the solid state by CD spectroscopy and
      energy minimization with the Monte Carlo method. The magnetic properties of both
      optically active and racemic alpha-NNs in solution and in the solid state were
      characterized by EPR spectroscopy and magnetic susceptibility measurement,
      respectively.

PMID- 14725463
TI  - Spectroscopic detection, reactivity, and acid-base behavior of ring
      dimethoxylated phenylethanoic acid radical cations and radical zwitterions in
      aqueous solution.
AB  - A product and time-resolved kinetic study of the one-electron oxidation of ring
      dimethoxylated phenylethanoic acids has been carried out at different pH values.
      Oxidation leads to the formation of aromatic radical cations or radical
      zwitterions depending on pH, and pK(a) values for the corresponding acid-base
      equilibria have been measured. The radical cations undergo decarboxylation with
      first-order rate constants (k(dec)) ranging from <10(2) to 5.6 x 10(4) s(-1)
      depending on radical cation stability. A significant increase in k(dec) (between
      10 and 40 times) is observed on going from the radical cations to the
      corresponding radical zwitterions. The results are discussed in terms of the ease
      of intramolecular side chain to ring electron transfer required for
      decarboxylation, in both the radical cations and radical zwitterions.

PMID- 14725464
TI  - Diastereoselective electrochemical carboxylation of chiral alpha-bromocarboxylic
      acid derivatives: an easy access to unsymmetrical alkylmalonic ester derivatives.
AB  - The diastereoselective electrochemical carboxylation of chiral N-(2
      bromoacyl)oxazolidin-2-ones has been studied. This reaction was carried out by
      cathodic reduction of the C-Br bond, in the presence of carbon dioxide, followed
      by treatment with diazomethane. The yields and the diastereomeric ratio of the
      two epimeric alkylmalonic acid derivatives are strongly affected by various
      factors: solvent-supporting electrolyte system, temperature, electrode material,
      electrolysis conditions, oxazolidinone moiety. The higher yields (88%) were
      obtained starting from N-(2-bromopropionyl)-4R-phenyloxazolidin-2-one 1a, but
      with poor diastereoselectivity (61:39). The two epimers were easily separated by
      flash chromatography. The best results were achieved using a different chiral
      auxiliary: Oppolzer's camphor sultam. Starting from 1j a good yield in
      carboxylated product was obtained (80%) with excellent diastereoselectivity
      (98:2). These chiral alkylmalonic acid derivatives are valuable building blocks
      in the synthesis of molecules with biological activity and of chiral propane-1,3
      diols derivatives.

PMID- 14725465
TI  - Synthesis and molecular recognition of pyrenophanes with polycationic or
      amphiphilic functionalities: artificial plate-shaped cavitant incorporating
      arenes and nucleotides in water.
AB  - Water-soluble pyrenophanes possessing polycationic or amphiphilic side chains
      have been developed as synthetic host molecules to investigate hydrophobic and/or
      pi-stacking interactions. By utilizing omega-acetalic alkyl side chains to retain
      solubility and versatility, water-soluble macrocyclic pyrenophanes could be
      easily obtained by Stille coupling, followed by conversion of the acetal groups
      to hydrophilic substituents. Among the pyrenophanes synthesized, hexaammonium-,
      bis(diazoniacrown)-, and tetrakis[octa(oxyethylene)]-derived ones showed enough
      solubility in pure water. The former two cationic pyrenophanes strongly
      recognized anionic arenes including nucleotides, while the latter neutral one
      associated with monopyrenyl guests regardless of their electric natures. The
      strength of recognition for nucleotides by bis(diazoniacrown)pyrenophane depended
      on the number of phosphate moieties, decreasing in the following order:
      triphosphate >> diphosphate approximately monophosphate.

PMID- 14725466
TI  - Total synthesis of macrosphelides A, B, and E: first application of ring-closing
      metathesis for macrosphelide synthesis.
AB  - A new synthetic route for macrosphelides A, B, and E based on ring-closing
      metathesis (RCM) was established. The substrates for RCM could be synthesized
      starting from commercially available chiral materials, methyl (S)-lactate and
      methyl (S)- or (R)-3-hydroxybutyrate, in good overall yields. In the
      investigation of the key RCM step, it was found that the steric factor around the
      reaction site significantly affected the reaction rate of macrocyclization. A
      detailed account regarding this synthetic study is described herein.

PMID- 14725467
TI  - Carbocations (M + H)(+) and oxidation dications (M(2+)) from benzo[a]pyrene and
      its nonalternant isomers azulenophenalenes: a theoretical (DFT, GIAO, NICS)
      study.
AB  - The arenium ions of protonation and the two-electron oxidation dications derived
      from benzo[a]pyrene (BaP) 1 and three of its nonalternant isomers namely
      azuleno[5,6,7-cd]phenalene 2 (a strong carcinogen reported to be as potent as
      BaP) azuleno[1,2,3-cd]phenalene 3 (a strong mutagen/weak carcinogen), and
      azuleno[4,5,6-cd]phenalene 4 (a weak mutagen) were studied by DFT at the B3LYP/6
      31G(d) level. The most favored sites for electrophilic attack were identified on
      the basis of relative protonation energies in the arenium ions. Computed NMR
      chemical shifts (GIAO NMR), the NPA-derived charges (and changes in charges), as
      well as NICS (and DeltaNICS) were employed to derive charge delocalization maps
      and to gauge relative aromaticity/antiaromaticity in the resulting carbocations
      and oxidation dications. Quantitative correlations between the experimental
      (superacid) (13)C data and GIAO chemical shifts, and between computed changes in
      charges and GIAO Deltadelta (13)C values were explored for benzo[a]pyrenium ion
      (1cH(+)) and its singlet oxidation dication (1(2+)) as representative cases. For
      the studied PAHs (1-4), formation of singlet dications were computed to be
      strongly favored except in 4 for which the triplet lies 5 kcal/mol lower than
      singlet. Relative carbocation stability data and the derived charge
      delocalization patterns are assessed in light of the available chemical and
      toxicological data on these compounds. The present study is the first of its kind
      to examine the carbocations and oxidation dications derived from biologically
      active nonalternant analogues of BaP for which no stable ion data are available.
      It also validates and extends the experimental data for BaP carbocation and
      oxidation dication and provides a means to gauge the success of GIAO NMR in
      predicting NMR data for PAH-arenium ions.

PMID- 14725468
TI  - Catalytic (2 + 2)-cycloaddition reactions of silyl enol ethers. A convenient and
      stereoselective method for cyclobutane ring formation.
AB  - An efficient catalytic (2 + 2)-cycloaddition reaction leading to the formation of
      cyclobutane rings has been devised. The process transforms silyl enol ethers and
      alpha,beta-unsaturated esters into polysubstituted cyclobutanes with a high
      degree of trans-stereoselectivity. Both the rate and stereoselectivity of the
      process can be controlled by the choice of the ester group and silyl
      substituents. The results of stereochemical studies show that the cycloaddition
      step in this reaction proceeds in a nonstereospecific manner and, thus, by a
      pathway involving sequential nucleophilic additions via a short-lived
      zwitterionic intermediate.

PMID- 14725469
TI  - Novel versatile synthesis of substituted tetrabenzoporphyrins.
AB  - A novel general synthetic route to tetraaryltetrabenzoporphyrins (Ar(4)TBP) with
      various peripheral functional groups is developed. The procedure includes (i)
      Barton-Zard condensation of 1-nitro- or 1-phenylsulfonylcyclohexenes with
      isocyanoacetic acid esters, (ii) condensation of the resulting 4,5,6,7
      tetrahydroisoindoles with aromatic aldehydes to give fused
      tetraaryltetracylohexenoporphyrins (Ar(4)TCHP), and (iii) aromatization of the
      metal complexes of Ar(4)TCHP's into the corresponding Ar(4)TBP's. Cu and Zn
      complexes of Ar(4)TBP's are further demetalated to give the corresponding
      Ar(4)TBP free bases. The overall yields for the sequence range from 15% to 40%,
      making the method suitable for the preparation of gram quantities of Ar(4)TBP's
      in a single run. The scope of the method, the selection of the peripheral
      substituents, the choice of the metal ions, and their influence on the yields of
      aromatization are discussed. The basic spectroscopic properties of newly
      synthesized Ar(4)TBP's and Ar(4)TCHP's are reported together with the first X-ray
      crystallographic structure of the NiAr(4)TBP complex.

PMID- 14725470
TI  - Simple synthesis of a weak nucleophilic base (4-ethyl-2,6-diisopropyl-3,5
      dimethylpyridine) evidencing a double Janus group effect.
AB  - By analogy with 2,6-di-tert-butylpyridine and its 4-methyl-substituted
      derivatives, which are nonnucleophilic bases, 4-ethyl-2,6-diisopropyl-3,5
      dimethylpyridine (4) is also such a base. The isopropyl groups (Janus-like
      groups) are forced by the neighboring methyl groups to turn their "tert-butyl
      analogue face" toward the heteroatom, thereby protecting it sterically against
      electrophilic attack. The synthesis proceeds in two stages via the corresponding
      pyrylium salt 3 that is obtained by alkene diacylation. X-ray data for 4, its
      picrate, and the hexafluorophosphate of 3 confirm that the ground-state
      conformation agrees with the Janus effect prediction. The chemical behavior of 4
      indicates that it is indeed a weak nucleophilic base, which is able to substitute
      the nonnucleophilic bases in organic syntheses. The compound 3 reacts at normal
      pressure with methylamine or ethylamine, forming N-alkylpyridinium salts. The
      cationic polymerization of isobutene in the presence of 4 was also investigated.

PMID- 14725471
TI  - Toward an artificial oxidative DNA photolyase.
AB  - The design, synthesis, structure, and binding affinity of two dioptic receptors
      for the selective molecular recognition of the cis,syn cyclobutane pyrimidine
      dimer are reported. The design is based on two 2,6-di(acetamino)pyridine
      recognition units that are covalently linked via triple bonds to an anthraquinone
      functional spacer unit. The convergent synthesis uses a modified Sonogashira
      reaction involving a zinc transmetalation as the key step. The crystal structure
      of one of the receptors reveals a supramolecular 1D polymer with strong
      interactions mediated by shape self-complementarity, pi-stacking, and hydrogen
      bonding between adjacent molecules. Hydrogen bonding between adjacent strands
      enforces a parallel orientation, which leads to a noncentrosymmetric crystal
      structure of the highly polar compound. The receptor has an association constant
      of K(a) = 1.0 x 10(3) M(-1) with the cis,syn pyrimidine dimer, whereas binding of
      the trans,syn isomer is approximately 1 order of magnitude weaker.

PMID- 14725472
TI  - An annulene-fused cyclopentadienide. A photochromic
      cyclopentadienodimethyldihydropyrene where the fused cyclopentadienide group
      resembles benzene in its effect on the dihydropyrene-metacyclophanediene valence
      isomerization.
AB  - The synthesis of the green cyclopentadiene-fused dimethyldihydropyrene 12 was
      achieved in 36% yield in 7 steps from the parent dihydropyrene 3. Reaction of 12
      with KH or LiCH(2)SiMe(3) gave the [14]annulene-fused cyclopentadienide anion
      quantitatively. In the (1)H NMR spectra, the internal methyl protons of 12 at
      delta -3.9, change dramatically on formation of anion 5, becoming deshielded to
      delta -1.82. This is caused by the reduction in diatropicity of the [14]annulene
      ring on fusion to the 6pi-cyclopentadienide ring. The anion is also a
      photochromic switch. Irradiation of the closed form 5 with visible light opens it
      to the open form 5', which reverts to the closed form 5 either with UV light or
      thermally. The switching behavior is between that of the parent 3/3' and the
      benzannelated system 4/4' and suggests that in its effect on the photoswitching,
      cyclopentadienide is behaving chemically similar to benzene.

PMID- 14725473
TI  - Remarkable rate acceleration of imidazole-promoted Baylis-Hillman reaction
      involving cyclic enones in basic water solution.
AB  - The Baylis-Hillman reaction of cyclic enones was greatly accelerated in basic
      water solution with imidazoles as catalysts, which resulted in short reaction
      time, high yields, and expanding substrate scopes. Bicarbonate solution was shown
      to be the optimal reaction medium for the reaction in this study. The apparent
      "enhanced basicity" of imidazoles accounted for the rate increase in alkaline
      solution.

PMID- 14725474
TI  - Evidence of enhanced reactivity of DAAP nucleophiles toward dephosphorylation and
      deacylation reactions in cationic gemini micellar media.
AB  - 4,4'-(Dialkylamino)pyridine (DAAP)-based compounds 1-4 catalytically cleave
      hydrophobic organophosphate and carboxylate esters in various host micellar
      aggregates at mildly alkaline pH. The role of the micellar reaction medium in
      such esterolytic reactions has been carefully examined in this work. The cationic
      gemini surfactant based micellar aggregates provide more than 1 order of
      magnitude better reaction medium for the above reactions than their conventional
      single-chain, single-charge, cationic cetyl trimethylammonium bromide (CTABr)
      micelles. The catalytic turnover behavior of DAAP nucleophiles in the presence of
      excess substrates is also retained in gemini micellar media.

PMID- 14725475
TI  - Regiocontrol in the oxidative radical fragmentation of benzilidene acetals and
      its mechanistic implications.
AB  - The NBS-mediated oxidative fragmentation of benzilidene acetals has been
      investigated with mechanistic probes 12, 14, and 18 designed to discriminate
      between the possible competitive pathways. Results indicate that fragmentation of
      the initial benzylic radical 19 does not occur spontaneously but that oxidation
      proceeds rapidly to give the benzyl bromide 20, which then fragments via a polar
      pathway. Reversed regiospecificity in the fragmentation is demonstrated for the
      first time through the incorporation of an allylic alcohol into the benzilidene
      acetal.

PMID- 14725476
TI  - Facile synthesis of 2-bromo-3-fluorobenzonitrile: an application and study of the
      halodeboronation of aryl boronic acids.
AB  - A scaleable synthesis of 2-bromo-3-fluorobenzonitrile via the NaOMe-catalyzed
      bromodeboronation of 2-cyano-6-fluorophenylboronic acid was developed. The
      generality of this transformation was demonstrated through the halodeboronation
      of a series of aryl boronic acids. Both aryl bromides and aryl chlorides were
      formed in good to excellent yields when the corresponding aryl boronic acid was
      treated with 1,3-dihalo-5,5-dimethylhydantoin and 5 mol % NaOMe.

PMID- 14725477
TI  - Bridged synthons from tetrabromocyclopropene: studies on the rearrangement of the
      primary Diels-Alder adduct with 2,5-dimethylfuran.
AB  - The reaction of tetrabromocyclopropene and furan leads directly to 8
      oxabicyclo[3.2.1]octadiene derivatives. It has been proposed that this involves
      an initial Diels-Alder reaction followed by rearrangement of the primary adduct.
      We have, for the first time, isolated a primary adduct and established through X
      ray crystallographic analysis that the adduct is the product of an exo-selective
      addition. Kinetic studies suggest the intermediacy of charged intermediates
      during the rearrangement.

PMID- 14725478
TI  - Titanocene-catalyzed regioselective carbomagnesation of alkenes and dienes.
AB  - A new method for regioselective carbomagnesation of alkenes and dienes has been
      developed by the use of a titanocene catalyst. This reaction proceeds efficiently
      at 0 degrees C in THF in the presence of Cp(2)TiCl(2) by the combined use of
      organic halides (R-X; R = alkyl, aryl and vinyl) and n-BuMgCl to afford benzyl,
      alpha-silylalkyl, or allyl Grignard reagents, which were trapped with various
      electrophiles. The present reaction involves (i) addition of carbon radicals
      toward alkenes or dienes in the carbon-carbon bond-forming step and (ii)
      transmetalation on Ti of benzyl-, alpha-silylalkyl-, or allyltitanocene with n
      BuMgCl in the carbon-magnesium bond-forming step. The scope and limitations of
      this reaction have also been examined.

PMID- 14725479
TI  - Reactions on a solid surface. A simple, economical, and efficient acylation of
      alcohols and amines over Al2O3.
AB  - Al(2)O(3) brings about a rapid acylation of a range of alcohols and amines with
      acid chlorides and acid anhydrides, respectively. Amines are easily Boc- and Cbz
      protected on reaction with Boc-anhydride and Cbz-Cl, respectively. The acylation
      of phenols is slow enough to allow chemoselective acylation of alcohols and
      amines in the presence of phenols.

PMID- 14725480
TI  - Highly effective fluorescent sensor for H2PO4(-).
AB  - A new anthracene dimer connected by two imidazolium moieties has been
      systematically designed and synthesized as a fluorescent chemosensor for
      selective binding of H(2)PO(4)(-) over other anions, which have been examined
      using fluorescence and (1)H NMR and rationalized with ab initio study.

PMID- 14725481
TI  - A novel two-carbon homologation with N-vinylacetamides and ethyl vinyl ether as
      acetaldehyde anion equivalents in the synthesis of 9H-xanthene, 9H-thioxanthene,
      and 9,10-dihydro-9-acridine carboxaldehydes.
AB  - An efficient synthesis of 9H-xanthene-9-carboxaldehyde (3a), 9H-thioxanthene-9
      carboxaldehyde (3b), and 9,10-dihydro-10-methyl-9-acridinecarboxaldehyde (3c) by
      a novel two-carbon homologation of xanthydrol (1a), thioxanthydrol (1b), and 9,10
      dihydro-10-methyl-9-acridinol (1c), respectively, using N-vinylacetamides (2a,b)
      or ethyl vinyl ether (2c) as acetaldehyde anion equivalents, is described.

PMID- 14725482
TI  - Theoretical and experimental studies on the thermal ring-opening reaction of
      cyclobutene having a stannyl substituent at the 3-position.
AB  - The ring-opening reaction of 3-(trimethylstannyl)cyclobutene gave a mixture of
      the (Z)- and (E)-1,3-dienes, whereas that of 3-tert-butylcyclobutene exclusively
      afforded the (E)-1,3-diene due to the steric influences. The contrasting
      rotational behaviors suggest that there is some effect operating with the 3
      stannylcyclobutene to stabilize the inward transition state, counteracting the
      steric influences. This contrasteric effect is ascribed to negative
      hyperconjugation. The stannyl group in the inward transition state accommodates
      electron density from the breaking sigma orbital of the cyclobutene into its low
      lying tin-carbon sigma orbital. Theoretical studies supported this
      interpretation.

PMID- 14725483
TI  - Intervention of phenonium ion in Ritter reactions.
AB  - The transformation of phenylethyl chloride to 3,4-dihydroisoquinolines is shown
      to proceed via phenonium ion. The evidence comes from a study of dideuterated
      analogue 4, and the monomethylated and dimethylated compounds 2 and 3.

PMID- 14725484
TI  - Volume efficacy and reduced influence on measures of coagulation using
      hydroxyethyl starch 130/0.4 (6%) with an optimised in vivo molecular weight in
      orthopaedic surgery : a randomised, double-blind study.
AB  - BACKGROUND AND OBJECTIVE: Different types of hydroxyethyl starch (HES) affect
      blood coagulation differently. We studied the effects of HES 130/0.4 on
      coagulation in major orthopaedic surgery in relation to the pharmacological
      parameter in vivo molecular weight. METHODS: 52 patients were randomly allocated
      to either HES 130/0.4 (6%, mean molecular weight 130 kDa, molar substitution 0.4)
      or HES 200/0.5 (6%, control) in a double-blind fashion. Colloidal volume
      requirements for intra- and postoperative haemodynamic stabilisation were
      compared. Safety analyses of this pharmacological study included a comparison of
      coagulation factor tests, in vivo molecular weight, and HES plasma
      concentrations. RESULTS: The colloidal volumes given were similar at the end of
      surgery (1602 +/- 569 for HES 130/0.4 vs 1635 +/- 567mL for HES 200/0.5), 5h
      later (1958 +/- 467 vs 1962 +/- 398mL), and up to the first postoperative day
      (2035 +/- 446 vs 2000 +/- 424mL). HES in vivo molecular weight at the end of
      surgery was 88,707 +/- 13,938 versus 158,374 +/- 33,933Da (p < 0.001) and 5h
      later was 86,663 +/- 16,126 versus 136,299 +/- 26,208Da (p < 0.001). In parallel
      to the lower in vivo molecular weight, factor VIII and von Willebrand factor
      returned to almost normal in the HES 130/0.4 group up to 5h postoperatively, but
      not in the control group (p < 0.05). Residual HES plasma concentrations after 24h
      were low in the HES 130/0.4 group (1.0 mg/mL), but higher in the control group
      (2.6 mg/mL). CONCLUSION: HES 130/0.4 and HES 200/0.5 were found to be similar
      with regard to volume efficacy. Sensitive coagulation parameters returned more
      rapidly to normal in the HES 130/0.4 group. Lower in vivo molecular weight and
      more rapid excretion of HES 130/0.4 are the likely explanations for the smaller
      influence on coagulation in this group.

PMID- 14725485
TI  - Weekly paclitaxel in elderly patients with advanced breast cancer: a dose-finding
      study.

PMID- 14725486
TI  - Clinical monitoring of tacrolimus after liver transplantation using pentamer
      formation assay and microparticle enzyme immunoassay.

PMID- 14725487
TI  - Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate,
      eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol.
AB  - Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer
      form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer
      contains two chiral centres and is being developed as an inhaled preparation for
      the treatment of respiratory disorders. Sepracor believes that arformoterol has
      the potential to be a once-daily therapy with a rapid onset of action and a
      duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England
      Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the
      purpose of preparing formulations of levosalbutamol and arformoterol. Phase II
      dose-ranging clinical studies of arformoterol as a longer-acting, complementary
      bronchodilator were completed successfully in the fourth quarter of 2000. Phase
      III trials of arformoterol began in September 2001. The indications for the drug
      appeared to be asthma and chronic obstructive pulmonary disease (COPD). However,
      an update of the pharmaceutical product information on the Sepracor website in
      September 2003 listed COPD maintenance therapy as the only indication for
      arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies
      were ongoing in 1600 patients. Sepracor estimates that its NDA submission for
      arformoterol, which is projected for the first half of 2004, will include
      approximately 3000 adult subjects. Sepracor stated in July 2003 that it had
      completed more than 100 preclinical studies and initiated or completed 15
      clinical studies for arformoterol inhalation solution for the treatment of
      bronchospasm in patients with COPD. In addition, Sepracor stated that the two
      pivotal phase III studies in 1600 patients were still progressing. In 1995,
      European patents were granted to Sepracor for the use of arformoterol in the
      treatment of asthma, and the US patent application was pending.

PMID- 14725488
TI  - CHF 3381.
AB  - CHF 3381 is an NMDA antagonist and monoamine oxidase inhibitor under development
      with Chiesi for the treatment of neuropathic pain. Preclinical studies show that
      the agent acts as a reversible and competitive inhibitor of human monoamine
      oxidases A and B. At the 1st Annual BioPartnering North America (BPN-2003) it was
      stated that CHF 3381 is being evaluated for the treatment of neuropathic pain.
      Preliminary data also suggested that CHF 3381 may have neuroprotective activity.
      In June 2003, Chiesi announced the completion of a phase I trial in France, and
      is proceeding with a proof-of-concept study in Denmark. CHF 3381 is covered by
      European patent application EP 951465 (expires on 15 July 2017), and US patent
      No. 6,114,391 (issued on 5 September 2000). Other patents are granted or pending
      in 20 countries. Chiesi also has rights to the European patent application for
      use of glycinamide derivatives (including CHF 3381) in the treatment of chronic
      pain.

PMID- 14725489
TI  - Ecraprost: AS 013, Circulase.
AB  - Ecraprost [AS 013, Circulase] is a prodrug of prostaglandin E(1) within lipid
      microspheres that is being developed in Japan by Mitsubishi Pharma Corporation
      and Asahi Glass. It was originally in development with Welfide Corporation. On 1
      October 2001, Welfide Corporation (formerly Yoshitomi) merged with Mitsubishi
      Tokyo Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a
      subsidiary of Mitsubishi Chemical. Taisho and Seikagaku Corporation had been
      involved in the development of ecraprost but discontinued their licences to do
      so. The effects of ecraprost on reperfusion injury, in preclinical studies, had
      been reported by Taisho. Ecraprost is in phase II in Japan and was in phase II in
      Europe for the treatment of peripheral arterial disease. It was also in a phase
      II study in the treatment of diabetic neuropathies. However, this is no longer an
      active indication. A phase III trial using a lipid emulsion of ecraprost
      [Circulase] is underway with Mitsubishi Pharma Corporation in the US, using
      ecraprost for the treatment of patients with severe peripheral arterial disease,
      which, because of decreased blood flow to the extremities, can lead to painful
      ulcers on the legs and feet and subsequent amputation. Alpha Therapeutic
      Corporation (a former subsidiary of Mitsubishi Pharma) was initially involved in
      trials of ecraprost in the US, but this responsibility has been taken over by the
      parent company.

PMID- 14725490
TI  - Exenatide: AC 2993, AC002993, AC2993A, exendin 4, LY2148568.
AB  - Exenatide [AC002993, AC2993A, AC 2993, LY2148568, exendin 4], a glucagon-like
      peptide-1 (GLP-1) agonist, is a synthetic exendin 4 compound under development
      with Amylin Pharmaceuticals for the treatment of type 2 diabetes. Both exendin 4
      and its analogue, exendin 3, are 39-amino acid peptides isolated from Heloderma
      horridum lizard venom that have different amino acids at positions 2 and 3,
      respectively. Exendins are able to stimulate insulin secretion in response to
      rising blood glucose levels, and modulate gastric emptying to slow the entry of
      ingested sugars into the bloodstream. Amylin Pharmaceuticals acquired exclusive
      patent rights for the two exendin compounds (exendin 3 and exendin 4) from the
      originator, Dr John Eng (Bronx, NY, US). On 20 September 2002, Amylin and Eli
      Lilly signed a collaborative agreement for the development and commercialisation
      of exenatide for type 2 diabetes. Under the terms of the agreement, Eli Lilly has
      paid Amylin a licensing fee of 80 million US dollars and bought Amylin's stock
      worth 30 million US dollars at 18.69 US dollars a share. After the initial
      payment, Eli Lilly will pay Amylin up to 85 US dollars million upon reaching
      certain milestones and also make an additional payment of up to 130 million US
      dollars upon global commercialisation of exenatide. Both companies will share the
      US development and commercialisation costs, while Eli Lilly will pick up up to
      80% of development costs and all commercialisation costs outside the US. Amylin
      and Eli Lilly will equally share profit from sales in the US, while Eli Lilly
      will get 80% of the profit outside the US and Amylin will get the rest. This
      agreement has also enabled Amylin to train its sales force to co-promote Lilly's
      human growth hormone Humatrope. Alkermes will receive research and development
      funding and milestone payments, and also a combination of royalty payments and
      manufacturing fees based on product sales. Alkermes undertakes the responsibility
      for the development of several initial formulations of the long-acting drug and
      manufacturing of the final product, while Amylin will be responsible for clinical
      trials, regulatory filings and worldwide marketing. The goal of the exenatide LAR
      programme is to develop a once-a-month injectable formulation of exenatide. In
      November 2003, Amylin announced positive results from the second of three
      pivotal, phase III studies that evaluated the effects of exenatide in combination
      with sulfonylureas in 377 randomised patients with type 2 diabetes. The design of
      the study was similar to that from the first study. The final third phase III
      study of exenatide was completed in November 2003. This study investigated the
      effects of exenatide in combination with metformin and sulfonylureas. Amylin and
      Eli Lilly announced that all of the pivotal phase III trials met the primary
      glucose control endpoint as measured by glycosylated haemoglobin. An NDA
      submission for exenatide is projected for mid-2004. A phase II, dose-ascending
      study in patients with type 2 diabetes was initiated in June 2002. This
      multicentre (US), double-blind, placebo-controlled study evaluated the safety,
      tolerability and the pharmacokinetic profile of exenatide LAR in up to 100
      patients with type 2 diabetes. A phase I study of exenatide LAR began in Europe
      in March 2001 and was completed in Q3 2001. A long-acting, sustained-release
      formulation of exenatide lowered both pre- and post-meal glucose concentration
      during a 24h period in patients with type 2 diabetes. In November 2002, analysts
      at Prudential Financial estimated that exenatide, pending approval, has the
      potential to reach sales of 477 million US dollars in 2006.

PMID- 14725491
TI  - Fozivudine: BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867.
AB  - Fozivudine [BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867] is a
      thioether lipid conjugate of zidovudine (AZT) in clinical development with
      Heidelberg Pharma Holdings for the potential treatment of HIV infection.
      Heidelberg Pharma's proprietary Linker-Cleavag-Enzyme Technology (LCE_Technology)
      is used to conjugate specific carriers to parent compounds, significantly
      improving their pharmacological, toxicological and/or clinical profile.
      LCE_Technology was originated at Boehringer Mannheim, which was acquired by, and
      integrated into, Roche. In 1999, when Heidelberg Pharma was founded, following a
      management buy-out from Roche Diagnostics GmbH, the new company acquired full
      ownership of the intellectual property and documentation related to various
      proprietary compounds, the LCE_Technology and its applications. According to
      Heidelberg Pharma's pipeline, published in August 2003, the product candidate,
      HDP 99.0002 (the company-specific code for fozivudine) will be in phase III
      development until early 2006, at which time the company hopes to file an NDA. A
      phase II study of fozivudine in 72 antiretroviral-naive patients with HIV
      infection was completed in the US and France by Roche.

PMID- 14725492
TI  - Huperzine A.
AB  - Huperzine A, an alkaloid isolated from Huperzia serrata, is a putative nootropic
      agent developed by the Chinese Academy of Sciences. Huperzine A is currently in
      phase III trials in China for the treatment of patients with Alzheimer's disease.
      The mechanism of action of huperzine A is suggested to be facilitated through the
      slow reversible inhibition of acetylcholinesterase. Marco Hi-Tech Joint Venture
      has exclusive worldwide marketing and distribution rights to huperzine A. Marco
      Hi-Tech Joint Venture is a corporation principally owned by Hi-Tech Pharmacal and
      Marco International, a global trading and finance firm formed to import huperzine
      A from China. Marco Hi-Tech Joint Venture also has rights to synthetic analogues
      of huperzine A. In July 2003, Savient Pharmaceuticals acquired the exclusive
      rights from Marco Hi-Tech to market huperzine A in Europe and the US. Clinical
      trials of huperzine A in elderly patients with age-associated memory loss are
      underway in the US, and a phase II study funded by an NCI grant is being planned.

PMID- 14725493
TI  - Insulin inhalation: NN 1998.
AB  - Aradigm Corporation has developed an inhaled form of insulin using its
      proprietary AERx drug delivery system. The system uses liquid insulin that is
      converted into an aerosol containing very small particles (1-3 micro in
      diameter), and an electronic device suitable for either the rapid transfer of
      molecules of insulin into the bloodstream or localised delivery within the lung.
      The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user
      on breathing technique to achieve the best results. Aradigm Corporation and Novo
      Nordisk have signed an agreement to jointly develop a pulmonary delivery system
      for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk
      has exclusive rights for worldwide marketing of any products resulting from the
      development programme. Aradigm Corporation will initially manufacture the product
      covered by the agreement, and in return will receive a share of the overall gross
      profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs
      incurred by Aradigm Corporation while both parties will co-fund final development
      of the AERx device. Both companies will explore the possibilities of the AERx
      platform to deliver other compounds for the regulation of blood glucose levels.
      Additionally, the agreement gives Novo Nordisk an option to develop the
      technology for delivery of agents outside the diabetes area. In April 2001,
      Aradigm Corporation received a milestone payment from Novo Nordisk related to the
      completion of certain clinical and product development stages of the AERx drug
      delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo
      Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated
      a pivotal phase III study with inhaled insulin formulation in September 2002.
      This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with
      insulin aspart. Both medications will be given three times daily before meals in
      addition to basal insulin administered once or twice daily. In 2003, the US FDA
      adopted new GMP guidelines requiring sterile production of inhalation products
      and their devices. Novo Nordisk, therefore, will need to repeat phase III studies
      following device optimisation. These studies may begin at the end of 2004 and
      will include efficacy studies for 6-12 months and safety studies for up to 2
      years (Lehman Brothers, Equity research, 7 August 2003). A phase IIb, 12-week
      clinical trial in 107 patients with type 2 diabetes was completed in the US. This
      trial was designed to compare the safety and efficacy of pulmonary insulin
      delivered via AERx iDMS, with intensified treatment with subcutaneous insulin
      administered at mealtimes. The results of the study positively compared pulmonary
      insulin with intensified subcutaneous insulin. Aradigm Corporation has a total of
      85 patents pertaining to its proprietary AERx drug delivery system. Among those
      granted patents, 18 patents cover pulmonary insulin formulation including the
      method of patient breathing technique during pulmonary delivery of insulin. This
      patent guides patients on how to breathe in certain defined ways to achieve an
      effective amount and reproducibility of blood levels of insulin.

PMID- 14725494
TI  - KMD 3213: KAD 3213, silodosin.
AB  - KMD 3213 [silodosin, KAD 3213] is an orally active alpha(1)-adrenoceptor
      antagonist under development with Kissei (Japan) for the treatment of dysuria
      associated with benign prostatic hyperplasia (BPH). Daiichi Pharmaceutical and
      Kissei are conducting phase III trials in Japan, while Kissei's US subsidiary,
      Kissei Pharma USA Inc., has completed early phase II trials with favourable
      results for the treatment of dysuria associated with benign prostatic hyperplasia
      (BPH). Kissei expects to file an NDA application in Japan in July 2004. Daiichi
      is also preparing a phase I trial in China with this compound for the treatment
      of dysuria associated with benign prostatic hyperplasia. According to Kissei's
      2003 Annual Report, they are currently preparing to license out the development
      and marketing rights for KMD 3213 in Europe and North America. In March 2002,
      Daiichi predicted that KMD 3213 has the potential to reach peak sales of
      approximately 10 billion Japanese yen.

PMID- 14725495
TI  - Motexafin gadolinium: gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex,
      GdT2B2, PCI 0120.
AB  - Motexafin gadolinium [gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex,
      GdT2B2, PCI 0120] is a radiosensitising agent developed for use in cancer
      therapy. It is cytotoxic in haematological malignancies by selectively localising
      in cancer cells that have high rates of metabolism. Motexafin gadolinium inhibits
      cellular respiration resulting in the production of reactive oxygen species and
      inducing apoptosis. It is being developed by Pharmacyclics in the US. Bulk
      motexafin gadolinium is supplied to Pharmacyclics by the US company, Celanese,
      through a manufacturing and supply agreement between the two companies. In June
      2003, at the 39th Annual Meeting of the American Society of Clinical Oncology
      (ASCO-2003), the importance of having an agent for the treatment of brain
      metastases from lung cancer was highlighted. Results of a phase III study were
      presented that showed that motexafin gadolinium treatment was associated with a
      delay in time to neurological and neurocognitive progression in lung cancer
      patients. This was an important finding, as 46.6% of lung cancer patients already
      have brain metastases at the time of initial diagnosis, compared with only 2.7%
      of breast cancer patients. Brain metastases are also often the only site of
      metastatic disease in patients with lung cancer. In December 2002, Pharmacyclics
      began a phase III trial of motexafin gadolinium in patients with brain metastases
      (brain cancer in phase table) from lung cancer in the US, Europe, Canada and
      Australia. The trial is known as the Study of neurologic progression with
      Motexafin gadolinium And Radiation Therapy (SMART) and will compare whole-brain
      irradiation with whole-brain irradiation plus motexafin gadolinium in 550
      patients. The primary efficacy endpoint is time to neurological progression and
      the secondary endpoints are survival and neurocognitive function. In January
      2003, the US FDA completed its Special Protocol Assessment (SPA) of the SMART
      trial with a positive result and by June 2003, enrollment had begun. In addition,
      phase I trials are underway in children with intrinsic pontine glioma and adults
      with head and neck, lung and pancreatic cancers. A phase II trial is also being
      conducted in the US in patients with glioblastoma multiforme. Enrollment in this
      trial has been completed and preliminary results have been reported.
      Pharmacyclics has completed enrollment and follow-up of adults in its pivotal
      phase III trial of motexafin gadolinium as a radiation sensitiser for the
      treatment of brain metastases. The trial was conducted at 35 centres in Europe,
      Canada and the US. Full results from this initial phase III trial were presented
      at the annual meeting of the American Society of Clinical Oncology (ASCO) in
      Orlando, Florida, USA, held in May 2002. Pharmacyclics also announced in October
      2002, at the 44th Annual Meeting of the American Society for Therapeutic
      Radiology and Oncology (ASTRO), that motexafin gadolinium significantly prolonged
      time to neurological progression when added to whole brain radiation therapy and
      reduced the number of deaths in patients with brain tumour. Pharmacyclics
      announced in September 2000 that it has initiated two NCI-sponsored phase I
      trials conducted under a Cooperative Research and Development Agreement (CRADA)
      between Pharmacyclics and the NCI. The first trial, conducted in patients with
      stage IIIA non-small cell lung cancer, was designed to determine the safety of
      two different dosing regimens of motexafin gadolinium during preoperative
      radiotherapy after induction chemotherapy. The second study was designed to
      examine the use of motexafin gadolinium in combination with stereotactic Gamma
      Knife radiosurgery in patients with primary glioblastoma mutiforme. Two phase I
      clinical trials have also been conducted for the treatment of newly diagnosed
      glioblastoma multiforme at the UCLA Jonsson Comprehensive Cancer Center, USA.
      These phase I studies were sponsored by the NCI and were conducted under a CRADA
      with the NCI. Pharmacyclics has also completed multicentre US phase II clinical
      trials of motexafin gadolinium fin gadolinium in patients with metastatic tumours
      of the brain who require whole brain radiotherapy. Motexafin gadolinium is in a
      phase II trial in patients with lymphomas and multiple myeloma in the US.

PMID- 14725496
TI  - Rostaporfin: PhotoPoint SnET2, Purlytin, Sn(IV) etiopurpurin, SnET2, tin ethyl
      etiopurpurin.
AB  - The photosensitiser rostaporfin [Purlytin trade mark, SnET2, tin ethyl
      etiopurpurin, Sn(IV) etiopurpurin, PhotoPoint SnET2] was developed by Miravant
      Medical Technologies (USA) for use in the company's PhotoPoint trade mark
      photodynamic therapy. The therapy relies on low power, non-thermal light produced
      by a solid-state diode laser, sourced from the device co-developing partner,
      Iredex Corporation. Mirvant is currently undergoing discussions for potential
      licensing agreements with leading ophthalmology companies for rostaporfin. In
      June 2002, Miravant and Bausch & Lomb signed a non-binding letter on intent. The
      companies are expected to jointly review phase III clinical data concerning
      rostaporfin. Following the review Bausch & Lomb may negotiate an exclusive
      worldwide license to develop and commercialise the agent for ophthalmological
      indications. Previously, in June 1995, Miravant granted Pharmacia & Upjohn (now
      Pfizer) an exclusive worldwide license for development and marketing of
      rostaporfin. However, this agreement was terminated in March 2002, at which time
      Miravant regained the rights to all assets related to rostaporfin. In April 2000,
      Monsanto merged with Pharmacia & Upjohn to form Pharmacia Corporation.
      Subsequently, on 16 April 2003, Pharmacia Corporation was acquired by, and merged
      into, Pfizer. Preclinical studies had been underway for other vision-threatening
      eye diseases, as it also has potential in the treatment of diabetic retinopathy
      and glaucoma. The US FDA had granted fast-track status to rostaporfin for the
      treatment of age-related macular degeneration in 1998.

PMID- 14725498
TI  - Predicting dental anxiety. The clinical value of anxiety questionnaires: an
      explorative study.
AB  - AIM: This was to explore the usefulness of the Dental Subscale of the Children's
      Fear Survey Schedule (CFSS-DS) and the Child Behaviour Checklist (CBCL), used
      prior to treatment, in relation to the actual behaviour displayed during
      treatment. METHODS: The study group was 26 children, referred to a special dental
      care clinic for behaviour management problems, mostly caused by dental fear.
      Questionnaires used were the parent versions of the Dental Subscale of the
      Children's Fear Survey Schedule (CFSS-DS) and the Child Behaviour Checklist
      (CBCL). Behaviour was registered on videotape and scored by independent observers
      using the modified Venham scale. Treatment consisted of a familiarization visit
      and two restorative sessions. RESULTS: There was a significant reduction in fear,
      based on pre and post treatment CFSS-DS scores, and also the child's fearful
      behaviour during the two restorative sessions appeared to be related. But no
      correlation was found between the CFSS-DS and the CBCL, nor between the CFSS-DS
      and the behaviour displayed during the treatment sessions. CONCLUSION: The
      child's anxious behaviour during actual restorative dental treatment is not so
      much related to its own anticipatory dental anxiety or the anxiety of the mother.
      Results support the role of a multifactorial model.

PMID- 14725499
TI  - Psychological aspects in paediatric dentistry: parental presence.
AB  - AIM: The scope of the present study has been the analysis of the main
      psychological approaches used during a first dental visit of a child to gain the
      necessary collaboration, focusing on the influence of parental presence during
      the visit. METHODS: The study was conducted on a group of 200 children divided
      into two sub-groups. In Group I the child was seen without the parent's presence
      and in Group II the parent was present throughout the visit. Assessment of
      behaviour was by a simple 'co-operative' or 'non-cooperative' in achieving a
      dental examination and prophylaxis. Statistical analysis was made by chi square
      and Fisher's exact test. RESULTS: In Group I (parent out) 89% of children were
      fully co-operative compared with 63% in Group II (parent present) which was
      significantly different (chi square 18.503, p<0.001). In addition 8% of children
      in Group II failed to return for any further dental care compared with 1% in
      Group I, which was also significantly different (Fisher's exact test p=0.1231).
      CONCLUSION: Parental presence affects a child's behaviour on an initial dental
      visit, which is better when the parent is excluded.

PMID- 14725500
TI  - A videotaped intervention to enhance child control and reduce anxiety of the pain
      of dental injections.
AB  - AIM: While the psychological literature shows that perceptions of
      uncontrollability contribute to anxiety and other pathologies, interventions that
      enhance perceived control have been shown to reduce anxiety. This study attempted
      to assess a brief videotape to enhance child perceived control in a dental
      setting. METHODS: 101 children aged 7-9 years completed warm-up procedures and
      viewed either: a) the experimental intervention, a 2 minutes video of a dentist
      explaining what an injection will feel like and proposing hand raising as a
      signal mechanism; or b) the control condition, a 2 minutes video of Disneyland.
      Fear of dental injections was assessed on a 10 cm visual analogue scale before
      and after the intervention. RESULTS: In the experimental group there was a
      significant fear reduction from pre- to post-intervention, while this was not the
      case in the control group. Children with higher pre-existing levels of fear
      benefited more from the intervention than children with lower levels of fear.
      CONCLUSION: The results of this pilot study suggest that intervention packages
      that impact child control have promise in lowering anxiety.

PMID- 14725501
TI  - Frequent exposure to invasive medical care in early childhood and operative
      dental treatment associated with dental apprehension of children at 9 years of
      age.
AB  - AIM: This was to study prospectively a cohort of children as to whether behaviour
      at a 3-year examination, exposure to medical care and operative dental treatment
      are associated with each other, and with the level of dental apprehension at 9
      years of age. METHODS: Data were collected at three subsequent dental
      examinations of 126 children (67 boys, 59 girls). Cooperation, general health
      condition and operative dental treatment during the preceding 3 years were
      obtained at dental examinations with 3-year intervals, i.e. at 3, 6 and 9 years
      of age. Children's dental apprehension was assessed at the age of 9 years. The
      data were analysed using an ordinal logistic regression model. RESULTS: Dental
      apprehension at 9 years of age was associated with frequent exposure to invasive
      medical care (p<0.001) and past experience of operative dental care (p<0.002),
      but not with cooperation at 3 years of age (p=0.124). CONCLUSION: Frequent
      invasive medical care in early childhood and operative dental treatment, tooth
      extractions in particular, are associated with dental apprehension at 9 years of
      age.

PMID- 14725502
TI  - An intervention program to reduce dental avoidance behaviour among adolescents: a
      pilot study.
AB  - AIM: To develop and test the methodology of an intervention to reduce avoidance
      of dental care among adolescents, and to measure the respondents' beliefs
      regarding the intervention (credibility and cognitions). METHODS: Based on a
      group comparison design a sample of 18 year olds (n=50) with dental non
      attendance behaviour was randomly selected to three experimental and one control
      group. Subjects were surveyed with one baseline questionnaire and one post
      intervention questionnaire, to evaluate their beliefs regarding the program. Two
      different instruments were tested: 1) cards representing different statements
      related to previous dental experiences, possible reasons for attending (pros) and
      not attending (cons) dental appointments, and preferences for future treatment.
      Cards were selected based on individual priority; 2) a brief, structured
      telephone interview based on Motivational Interviewing. The instruments were
      tested separately (groups I and II) and in combination (group III). Subjects in
      the control group (group IV) were given conventional health education. RESULTS:
      Subjects in the experimental groups had significantly higher credibility scores
      to the statement "How much easier do you perceive dental treatment to be for you,
      based on this program", compared with the control group (p<0.05). They had also
      more positive beliefs to the statement "I think the interviewer liked to talk to
      me" (p<0.05) than controls. CONCLUSION: A questionnaire sent to non-attending
      adolescents followed by a brief telephone call based on Motivational Interviewing
      appears to be a credible intervention for adolescents avoiding dental care.

PMID- 14725503
TI  - Reliability and validity of measures used in assessing dental anxiety in 5- to 15
      year-old Croatian children.
AB  - AIM: The aim of the study was to evaluate reliability and validity of different
      questionnaires and predict related causes, as concomitant factors in assessing
      different aspects of children's dental anxiety. STUDY DESIGN: Children were
      interviewed on dental anxiety, dispositional risk factors and satisfaction with
      the dentist after dental treatment had been accomplished. Parents were
      interviewed on dental anxiety as well. METHODS: The study population included 165
      children (91 boys) aged 5 to 15 years, referred to a university dental clinic by
      general dental practitioners because of a history of fear and uncooperative
      behaviour during previous dental visits. Children were treated by two dentists,
      both experienced in treating fearful children. STATISTICS: Statistical analysis
      was performed in Statistics for Windows, Release 5.5 and Release 7.5. Pearson's
      correlation coefficients were calculated for validity and Cronbach alpha for
      reliability of the measures. Spearman Brown prophecy formula was used for
      correction of the alpha scores. Results The children's total average CFSS-DS
      score was 27.02, with no significant difference with respect to gender. The
      highest Cronbach alpha scores regarding reliability were obtained for the S-DAI,
      the CFSS-DS and the PDAS. Pearson's correlations regarding validity presented
      significant correlations between the CMFQ, the CDAS and the S-DAI, between the
      OAS, the CDAS and the S-DAI, as well as between the OAS and the DVSS-SV.
      CONCLUSION: Previous negative medical experience had significant influence on
      children's dental anxiety, supporting Rachman's conditioning theory. Anxious
      children were more likely to show behaviour problems (aggression) and more
      introvert in expressing their judgement regarding the dentist. Both the S-DAI and
      the CFSS-DS, which were standardized in the Croatian population sample, showed
      the highest reliability in assessment of children's dental anxiety.

PMID- 14725504
TI  - A comparison of different kinds of European chocolates on human plaque pH.
AB  - AIM: To investigate the acidogenic response of plaque with various European
      chocolates of varying cocoa contents. METHODS: 14 subjects participated in the
      study. On each test day plaque pH measurements were taken at baseline and at 2,
      5, 10, 15, 20 and 30 minutes after challenge with the test chocolates or control
      foods. A plaque sample was removed from the buccal surfaces of posterior teeth
      representing all quadrants, within 30 seconds. The plaque pH was measured on an
      ISFET electrode connected to a Sentron 2001 pH system. The test chocolates were:
      Diet chocolate (DC), Plain European chocolate (PEC 70% cocoa), Plain English
      chocolate (PenC 34% cocoa), Milk English chocolate (MenC 20% cocoa), Milk
      European chocolate (MEC 30% cocoa), White chocolate (WC no cocoa), Milk chocolate
      with hazelnuts (MHC 20% cocoa). 15 g of each chocolate was consumed by the
      volunteers and 10 ml of 10% sucrose and sorbitol solutions were included as
      controls. RESULTS: The data were analysed for: minimum pH, area below baseline,
      area below "critical pH", time spent below "critical pH" and Acidogenic Potential
      Index (API). DC was found to be significantly different to sucrose and all the
      other test chocolates, and similar to sorbitol for all the parameters studied.
      The area below baseline plaque pH was also significantly smaller for PEC
      (p<0.006) and MHC (p<0.028) as compared with sucrose. The mean area below the
      "critical pH" (5.7) for PEC and MHC was lower at 0.20-/+0.34 and 0.60-/+1.40
      respectively, compared with sucrose at 1.38-/+1.03, but not statistically
      significant. The API of DC, PEC, PEnC, MEnC, MEC, WC and MHC was 0.03, 0.41,
      0.66, 0.93, 0.94, 0.88 and 0.45 respectively compared with an API of 1.00 of
      sucrose. CONCLUSION: Diet chocolate was found to have no acidogenic effect on
      dental plaque. Also, the PEC and MHC had a lower acidogenic potential compared
      with sucrose.

PMID- 14725505
TI  - Rare compound odontoma of the mandible in a 7-year-old child: case report.
AB  - BACKGROUND: A compound odontoma is a mixed tumor of odontogenic origin, in which
      both ectodermal and mesenchymal cells exhibit complete differentiation, resulting
      in the formation of tooth structures. It occurs with equal frequency in both
      sexes, and is often initially asymptomatic. CASE REPORT: A 7-year-old boy was
      recently examined in our Department for management of a compound odontoma.
      Surgical treatment was invasive because of the size of the lesion, but it was
      possible to use interceptive orthodontic treatment to restore the dental arch.

PMID- 14725506
TI  - A functional chimaeric S-layer-enhanced green fluorescent protein to follow the
      uptake of S-layer-coated liposomes into eukaryotic cells.
AB  - The chimaeric gene encoding a C-terminally truncated form of the S-layer protein
      SbpA of Bacillus sphaericus CCM 2177 and the EGFP (enhanced green fluorescent
      protein) was ligated into plasmid pET28a and cloned and expressed in Escherichia
      coli. Just 1 h after induction of expression an intense EGFP fluorescence was
      detected in the cytoplasm of the host cells. Expression at 28 degrees C instead
      of 37 degrees C resulted in clearly increased fluorescence intensity, indicating
      that the folding process of the EGFP moiety was temperature sensitive. To
      maintain the EGFP fluorescence, isolation of the fusion protein from the host
      cells had to be performed in the presence of reducing agents. SDS/PAGE analysis,
      immunoblotting and N-terminal sequencing of the isolated and purified fusion
      protein confirmed the presence of both the S-layer protein and the EGFP moiety.
      The fusion protein had maintained the ability to self-assemble in suspension and
      to recrystallize on peptidoglycan-containing sacculi or on positively charged
      liposomes, as well as to fluoresce. Comparison of fluorescence excitation and
      emission spectra of recombinant EGFP and rSbpA(31-1068)/EGFP revealed identical
      maxima at 488 and 507 nm respectively. The uptake of liposomes coated with a
      fluorescent monomolecular protein lattice of rSbpA(31-1068)/EGFP into HeLa cells
      was studied by confocal laser-scanning microscopy. The major part of the
      liposomes was internalized within 2 h of incubation and entered the HeLa cells by
      endocytosis.

PMID- 14725508
TI  - Mutation of cysteine 214 in Gi1 alpha subunit abolishes its endogenous GTPase
      activity.
AB  - The functional consequences of the mutation of a conserved Cys-214 in Galpha(i1)
      have been investigated. We reported herein that substitutions of Cys-214 of
      Galpha(i1) to either alanine or tryptophan abolished the intrinsic GTPase
      activity. Free phosphate release from [32P]GTP-bound Galpha(i1) C214A or [32P]GTP
      bound Galpha(i1) C214W was at least 30-fold lower than that of the wild-type
      Galpha(i1) in single-turnover GTPase assays. Consistently, tryptic proteolysis of
      C214A and C214W proteins showed that they were partially protected by GTP,
      further confirming that the GTPase activity in both mutant proteins was impaired.
      Expression of C214A or C214W mutants in Chinese hamster ovary K1 cells caused
      significant inhibition of forskolin-stimulated adenylate cyclase activity.
      However, the mutations did not significantly affect the GTP[S] (guanosine 5'
      [gamma-[35S]thio]triphosphate)-binding activity. Both C214A and C214W mutants
      serve as good substrates for pertussis toxin-catalysed ADP ribosylation,
      indicating that they interact well with betagamma subunits. Moreover, RGS4
      protein, a GTPase-activating protein for Galpha(i1), cannot interact with Cys-214
      mutants even in the presence of AlF4-, which induces the transition state of
      Galpha. In summary, our findings suggest that C214A or C214W are GTPase-deficient
      mutants and can functionally serve as constitutively active forms of Galpha(i1)
      in cells.

PMID- 14725509
TI  - A simple method for the production of recombinant proteins from mammalian cells.
AB  - Expression of recombinant proteins in mammalian cells is useful for obtaining
      products with normal post-translational modifications. We describe a simple and
      economical method for the production of milligram levels of proteins in murine
      fibroblasts. Retroviral or LIPOFECTAMINE (Gibco Laboratories) transduction was
      employed to generate stable murine-fibroblast producer cells. Confluent cultures
      of stable fibroblast clones were maintained for up to 1 month in 0.5% serum.
      Culture medium was collected every 2-3 days and polyhistidine-tagged proteins
      were purified by ammonium sulphate precipitation and Ni(2+)-nitrilotriacetic acid
      affinity chromatography. Highly pure, active, glycosylated recombinant proteins,
      including human beta-glucuronidase, mouse beta-glucuronidase, aminopeptidase N
      (CD13) and a single-chain antibody-enzyme fusion protein, were obtained with
      yields of 3-6 mg/l of culture medium. Fc-tagged proteins were also produced and
      purified in a single step by Protein A affinity chromatography with yields of 6
      12 mg/l. The techniques described here allow simple and economical production of
      recombinant mammalian proteins with post-translational modifications.

PMID- 14725510
TI  - Checking anaesthetic equipment and the Expert Group on Blocked Anaesthetic Tubing
      (EGBAT).

PMID- 14725507
TI  - Hormone-sensitive lipase--new roles for an old enzyme.
AB  - Although described initially as an intracellular adipocyte-specific
      triacylglycerol lipase, it is now clear that HSL (hormone-sensitive lipase) is
      expressed in multiple tissues and plays a number of roles in lipid metabolism,
      including that of a neutral cholesteryl ester hydrolase. The major isoform is a
      single polypeptide with a molecular mass of approx. 84 kDa and which comprises
      three major domains: a catalytic domain, a regulatory domain encoding several
      phosphorylation sites and an N-terminal domain involved in protein-protein and
      protein-lipid interactions. The activity of HSL is regulated acutely by several
      mechanisms, including reversible phosphorylation by a number of different protein
      kinases, translocation to different sites within the cell and interaction with a
      number of proteins, some of which may serve to direct the inhibitory products of
      HSL away from the protein. It is also apparent from work with HSL null mice that
      more than one enzyme species may be classified as a hormone-sensitive lipase. The
      possible presence of HSL in macrophages remains controversial, and the role of
      the protein in pancreatic beta-cells has yet to be fully elucidated. Altered
      expression of HSL in different cell types may be associated with a number of
      pathological states, including obesity, atherosclerosis and Type II diabetes.

PMID- 14725511
TI  - Continuous haemodynamic monitoring using transoesophageal Doppler during acute
      normovolaemic haemodilution in patients with coronary artery disease.
AB  - Transoesophageal Doppler monitoring allows non-invasive assessment of stroke
      volume. We studied haemodynamic changes during acute normovolemic haemodilution
      (ANH) in anaesthetised patients with coronary artery disease. Twenty patients
      were randomly assigned to either ANH or a control group. During ANH, a mean (SD)
      blood volume of 15.3 (3.4) ml.kg(-1) was withdrawn decreasing systemic oxygen
      delivery from 12.7 (3.3) to 9.3 (1.8) ml.kg(-1).min(-1) (p < 0.001). In the
      control group, haemodynamic data remained unchanged, whereas in the ANH group,
      stroke volume and central venous pressure increased significantly (mean = +21 ml
      [95% CI: 18-25 ml.min(-1)]; mean = +2.5 mmHg [95% CI: 2.2-2.8 mmHg],
      respectively) and heart rate decreased (mean = -6 beat.min(-1)[95% CI: 6-8
      beat.min(-1)], p < 0.05). According to the Frank-Starling relationship,
      individual changes in stroke volume compared with central venous pressure fitted
      a quadratic regression model (R2 > 0.91). A reduced viscosity associated with ANH
      resulted in improved venous return, higher cardiac preload and increased cardiac
      output. In summary, this study demonstrated that ANH to a haemoglobin value of
      8.6 g.dl(-1) was well tolerated in patients with coronary artery disease.

PMID- 14725512
TI  - The effect of pre-operative administration of midazolam on the development of
      intra-operative hypothermia.
AB  - (Midazolam is often used for premedication; it is known to promote vasodilation
      and may therefore affect redistribution of heat during surgery. We examined the
      effect of pre-operative administration of midazolam on the development of intra
      operative hypothermia. Forty-five patients were randomly allocated to one of
      three groups to receive no premedication (Group C), IM midazolam 0.04 mg.kg(-1)
      (Group M1) or 0.08 mg.kg(-1) (Group M2) 30 min prior to anaesthesia. Sedation
      levels were assessed, and then general anaesthesia was induced and maintained
      using propofol and fentanyl. During surgery, core temperature, which was similar
      for the three groups prior to induction of anaesthesia, decreased significantly
      less in the midazolam groups M1 and M2 compared to the control group C. Patients
      who were more heavily sedated prior to induction of anaesthesia, had
      significantly lower core temperatures peri-operatively than those who were less
      sedated, and core temperatures in unpremedicated patients fell to significantly
      lower levels during surgery than those who were drowsy. We conclude that pre
      operative administration of midazolam produces an effect on the development of
      peri-operative hypothermia. We found that moderate pre-operative sedation reduces
      the peri-operative heat loss, possibly by affecting core-to-peripheral heat
      distribution.

PMID- 14725513
TI  - The influence of esmolol on the dose of propofol required for induction of
      anaesthesia.
AB  - Cardiac output may be an important determinant of the induction dose of
      intravenous anaesthetic. Esmolol is known to reduce cardiac output, and we
      examined its effect on the propofol dose required for induction of anaesthesia.
      The size of the effect seen with esmolol was compared with midazolam co
      induction. Sixty patients were randomly allocated to placebo (saline), esmolol
      (1mg x kg(-1) bolus, followed by an infusion at 250 microg x kg(-1)min(-1)) or
      midazolam (0.04 mg x kg(-1)) groups. Induction of anaesthesia commenced 3 min
      following the administration of the study drug, using a Diprifusor set to achieve
      plasma propofol concentrations of 10 microg x ml(-1) at 5 min. The primary end
      point used was the propofol dose per kg at loss of response to command. The mean
      (SD) propofol dose for each group was 2.38 (0.48) mg x kg(-1) for placebo, 1.79
      (0.36) mg x kg(-1) for esmolol and 1.34 (0.35) mg x kg(-1) for midazolam (all
      means significantly different; p < 0.0005). We found that predosing with esmolol
      reduces the propofol requirements for induction of anaesthesia by 25%.

PMID- 14725514
TI  - Patient maintained sedation for colonoscopy using a target controlled infusion of
      propofol.
AB  - In this study, we evaluated safety and recovery using a patient maintained,
      target controlled infusion of propofol for sedation in 20 patients undergoing
      colonoscopy. Using a handset with a two-minute lockout interval, patients could
      make 0.2 micro g.ml(-1) increments to an initial target plasma concentration of 1
      micro g.ml(-1) up to a maximum 4.5 micro g.ml(-1). Four patients became
      oversedated but required no airway or circulatory interventions. Subjects had a
      significant reduction in mean (SD) heart rate: 78.7 (15) vs. 69.8 (13.5) (p <
      0.001) and in systolic blood pressure 121.1 (13.2) mmHg vs. 96.5 (8.6) mmHg (p <
      0.001). Choice reaction time testing 15 min after colonoscopy showed a
      significant median (IQR [range]) rise of 162 (- 16, 383.3 [-199-859]) ms (p <
      0.05). Six patients had faster reaction times postcolonoscopy. All patients
      denied unpleasant recall and were satisfied with the system. Although
      oversedation was a problem in this model, we conclude that patient maintained
      propofol sedation could be possible for colonoscopy.

PMID- 14725515
TI  - Comparison of patient-controlled epidural bolus administration of 0.1%
      ropivacaine and 0.1% levobupivacaine, both with 0.0002% fentanyl, for analgesia
      during labour.
AB  - The aim of the study was to compare the relative potencies and clinical
      characteristics of epidural ropivacaine and levobupivacaine in labour using
      patient-controlled epidural analgesia (PCEA). In a randomised double-blinded
      study, 60 ASA I or II primigravidae requesting epidural analgesia in early labour
      were allocated to receive either 0.1% ropivacaine with fentanyl 0.0002% or 0.1%
      levobupivacaine with 0.0002% fentanyl via a patient-controlled analgesia pump.
      Analgesia was established with 15 ml of study solution and maintained using 5-ml
      boluses of study solution with a 5-min lockout interval. There were no
      significant differences in onset time, duration and quality of analgesia, motor
      and sensory blockade, local anaesthetic consumption, mode of delivery, neonatal
      outcome or maternal satisfaction between the groups. We conclude that 0.1%
      ropivacaine with 0.0002% fentanyl and 0.1% levobupivacaine with 0.0002% fentanyl
      are clinically indistinguishable for labour analgesia and appear
      pharmacologically equipotent when using PCEA.

PMID- 14725516
TI  - Synacthen Depot for the treatment of postdural puncture headache.
AB  - We conducted a prospective, randomised, double-blind trial to study the effect of
      Synacthen Depot in 18 parturients with postdural puncture headache following
      deliberate or accidental dural puncture. Women were randomly allocated to receive
      either Synacthen Depot 1 mg (1 ml) or 0.9% saline 1 ml intramuscularly. Using a
      10-cm visual analogue scale, severity of headache was measured before and at
      intervals until 48 h after injection. There was no difference in the severity of
      headache or requirement for epidural blood patch. We conclude that there is no
      advantage to the use of Synacthen Depot 1 mg for the treatment of postdural
      puncture headache.

PMID- 14725518
TI  - Watson and Crick 50 years on. From double helix to pharmacogenomics.
AB  - The second half of the 20th century has seen quantum leaps in our understanding
      of molecular biology. The technological advances, which facilitated the recent
      successful completion of the Human Genome Project, have provided the tools for
      deciphering the complexity of the human condition. At present, the function of
      only 50% of genes is known. However, as understanding of the human genome
      improves, a plethora of gene targets for treating disease will be uncovered -
      leading to therapies which will be considered revolutionary. Genome related
      science has begun to impact almost every facet of medicine including anaesthesia
      and intensive care. Better understanding of interindividual differences will
      enable better prediction of illness susceptibility as well as response to
      treatment. These insights will permit therapies to be tailored to individuals or
      racial groups. At present, there is only rudimentary knowledge of factors
      controlling gene regulation, but in the future, better understanding of gene
      environment interactions and gene expression will enable pharmaceutical companies
      to develop new therapies and permit clinicians to optimise their effects, without
      recourse to current laborious testing regimens. As genomic science progresses,
      new ethical, legal, social and philosophical dilemmas will also continue to
      emerge.

PMID- 14725517
TI  - Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting
      prophylaxis: a randomised placebo-controlled patient and observer blind trial.
AB  - This randomised, placebo-controlled, patient and observer blinded trial was
      conducted to determine whether acupuncture at the acupuncture point P6 is
      effective in preventing postoperative nausea and vomiting (PONV) compared to
      placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or
      breast surgery were randomly assigned to two groups receiving either acupuncture
      (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of
      surgery and included two subgroups receiving intervention either before or after
      induction of anaesthesia. The incidence of PONV and/or antiemetic rescue
      medication within 24 h after surgery was the main outcome measure which showed no
      statistically significant difference between groups (43.7% acupuncture, 50.9%
      placebo, p = 0.27). The differences were more pronounced for patients having
      gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for
      those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The
      secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6%
      to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications
      of acupuncture before compared to after induction of anaesthesia.

PMID- 14725519
TI  - Improving anaesthetists' communication skills.
AB  - The attitude, behaviour and communication skills of specialised doctors are
      increasingly recognised as important and they have been identified as training
      requirements. We designed a programme to teach communication skills to doctors in
      a University Department of Anaesthesia and evaluated its effect on patient
      outcomes such as satisfaction and anxiety. The 20 h programme was based on
      videotaped reviews of actual pre-operative visits and role-playing. Effects on
      patient satisfaction and pre-operative anxiety were assessed using a patient
      questionnaire. In addition, all participating anaesthetists assessed the
      training. We provide evidence that the training increased patient satisfaction
      with the pre-operative anaesthetic visit. Training also decreased anxiety
      associated with specific aspects of anaesthesia and surgery, but the effect was
      rather small given the intense programme. The anaesthetists agreed that their
      interpersonal skills increased and they felt better prepared to understand
      patients' anxieties. Communication skills training can increase patient
      satisfaction and decrease specific anxieties. The authors conclude that in order
      to better demonstrate the efficacy of such a training programme, the particular
      communication skills of anaesthetists rather than indirect patient outcome
      parameters should be measured.

PMID- 14725520
TI  - Comparison of the Williams Airway Intubator and Ovassapian Fibreoptic Intubating
      Airway for fibreoptic orotracheal intubation.
AB  - A randomised study was carried out in 60 anaesthetised patients with no evidence
      of airway difficulties, to compare the Williams Airway Intubator and the
      Ovassapian Fibreoptic Intubating Airway for bronchoscopic view and ease of
      railroading a tracheal tube during fibreoptic orotracheal intubation. The
      Williams Airway Intubator provided a better view of the glottis (41 (68.3%)
      unobstructed views) than the Ovassapian Fibreoptic Intubating Airway (15 (25%)
      unobstructed views; p < 0.0001) and a shorter time was needed to complete
      bronchoscopy (median (95% CI) difference 4 s (1-7); p = 0.01). Four (6.7%)
      bronchoscopies failed using the Williams Airway Intubator compared with 26
      (43.3%) using the Ovassapian Fibreoptic Intubating Airway (p < 0.0001). Both
      airways provided similar intubating conditions when the glottis was visible.

PMID- 14725521
TI  - Latex-free reservoir bags: exchanging one potential hazard for another.
AB  - The reservoir bag on the anaesthetic breathing circuit is a safety feature that
      can protect the patient. It is highly distensible, pressures within the breathing
      circuit rarely exceeding 3.9 kPa (40 cmH2O) even when the adjustable pressure
      limiting valve is inadvertently left closed. In providing a safe latex-free
      environment in our anaesthetic rooms, the traditional latex rubber reservoir bag
      is substituted by a latex-free one. To investigate the safety features of several
      latex-free reservoir bags already in use in our hospital, we assessed the in
      circuit pressures obtained at stepped fresh gas flows using a lung simulator.
      Four out of five of the latex-free bags exceeded pressures of 4.4 kPa (45 cmH2O),
      raising the possibility that, in trying to avoid an occupational hazard, we might
      be compromising patient safety. We found that, of the five latex-free systems we
      tested, only the Intersurgical complete respiratory system provided an adequate
      safety mechanism for the patient and thus did not potentially compromise patient
      safety.

PMID- 14725522
TI  - Another look at Dumfries.
AB  - Following William Morton's demonstration of ether anaesthesia in the
      Massachusetts General Hospital in October 1846, the first major operation in the
      Old World is credited to Robert Liston at University College Hospital on 21
      December 1846. It has been suggested that a similar operation took place in
      Dumfries on 19 December 1846. The existing evidence is reviewed and new evidence
      from newspapers and hospital annual reports is presented. This evidence does not
      support the Dumfries claim.

PMID- 14725523
TI  - Kinetics of sevoflurane uptake by the brain.

PMID- 14725524
TI  - Remifentanil to reduce pain on injection of propofol.

PMID- 14725525
TI  - 'Blind' epidural blood patch for spontaneous intracranial hypotension.

PMID- 14725526
TI  - Trouble with a TOE.

PMID- 14725527
TI  - A new device for easier handling of the transoesophageal echocardiography probe.

PMID- 14725528
TI  - Temperature measurement after severe head injury.

PMID- 14725529
TI  - Air emphysema in the neck after excision of a thyroglossal cyst.

PMID- 14725530
TI  - Alpha agonists for anaphylaxis.

PMID- 14725531
TI  - Inadvertent myocardial biopsy by a trapped Seldinger wire.

PMID- 14725532
TI  - Inducing anaesthesia in the operating theatre.

PMID- 14725533
TI  - A rare side-effect of intravenous salbutamol.

PMID- 14725534
TI  - Shoulder supports, brachial plexus injury and head-down tilt.

PMID- 14725535
TI  - Ventilator-assisted nasotracheal intubation.

PMID- 14725536
TI  - Easier nasogastric tube insertion.

PMID- 14725537
TI  - Packaging of generic diclofenac (corrected from diclofeanc) suppositories.

PMID- 14725538
TI  - PCA in a patient with bilateral upper limb weakness.

PMID- 14725539
TI  - Intravenous magnesium sulphate and salbutamol for asthma.

PMID- 14725540
TI  - Anaesthesia for quinsy.

PMID- 14725541
TI  - The nasal intubation aid.

PMID- 14725542
TI  - Preparation for terrorist attacks.

PMID- 14725543
TI  - Logo for AAGBI.

PMID- 14725544
TI  - A response to 'Sudden deaths during hip hemi-arthroplasty', Parry G, Anaesthesia
      2003; 58: 922-23.

PMID- 14725545
TI  - In response to 'Difficult airway alert', Dunstan C R and Caesar H, Anaesthesia
      2003; 58: 918-19.

PMID- 14725547
TI  - A response to 'Pharmacokinetics of sevoflurane uptake into the brain and body',
      Lu C C, Tsai C S, Ho S T, Chen W Y, Wong C S, Wang J J, Hu O Yp and Lin C Y,
      Anaesthesia 2003; 58: 951-56.

PMID- 14725548
TI  - A response to 'The use of remifentanil for intubation in paediatric patients
      during sevoflurane anaesthesia guided by Bispectral Index (BIS) monitoring',
      Weber F, Fussel U, Gruber M and Hobbhahn J, Anaesthesia 2003; 58: 746-55.

PMID- 14725549
TI  - A response to 'Whose distress is it anyway? "fetal distress" and the 30-minute
      rule', Yentis S M, Anaesthesia 2003; 58: 732-34.

PMID- 14725550
TI  - A response to 'Avoiding adverse outcomes when faced with "difficulty with
      ventilation"', Bell D, Anaesthesia 2003; 58: 945-948.

PMID- 14725552
TI  - A response to 'Consent and anaesthetic risk', Jenkins K and Baker A B,
      Anaesthesia 2003; 58: 962-84.

PMID- 14725553
TI  - A response to 'Patient safety', Levison A, Anaesthesia 2003; 58: 1236, and 'Sleep
      deprivation and performance', Price S R, Anaesthesia 2003; 58: 1238-9.

PMID- 14725554
TI  - A response to 'Bougie trauma--it is still possible', Prabhu A, Pradham P, Sanaka
      R and Bilolikar A, Anaesthesia 2003; 58: 811-12.

PMID- 14725560
TI  - Recipients of the 2003 ASRI Awards.

PMID- 14725561
TI  - Shall we properly re-examine the status of allogeneic lymphocyte therapy for
      recurrent early pregnancy failure?
AB  - PROBLEM: How to evaluate immunological therapy advocated for recurrent
      spontaneous abortion and implantation failure. I was invited to comment on the
      opinion article of Chaouat (AJRI December 2003). METHODS: A critical examination
      of key beliefs and application of the principles of evidence and logic utilizing
      current data. RESULTS AND CONCLUSIONS: Although rationale has no bearing on
      efficacy of proposed treatments and is not sufficient justification for routine
      practice, insufficient attention to data concerning patient selection,
      insufficient attention to treatment methodology, and lack of full disclosure in
      some clinical trials needs to be corrected. A more systematic collection of
      follow-up data is needed.

PMID- 14725562
TI  - NF-kappaB activation at implantation window of the mouse uterus.
AB  - PROBLEM: Nuclear factor kappa B (NF-kappaB) is one candidate transcriptional
      modulator, which might regulate many kinds of molecules that play sequential
      roles at implantation in the endometrium. However, temporal and spatial
      activation of NF-kappaB at implantation window is unknown. METHODS: Activation of
      NF-kappaB in the mouse uterus was determined by electrophoretic mobility shift
      assays. Localization of p50 and p65, components of NF-kappaB, was analyzed by
      immunohistochemistry. RESULTS: NF-kappaB was activated in the proestrus and
      estrus phases in non-pregnant uterus. In the pregnant uterus, NF-kappaB was
      activated after day 1.5 post-coitum, and the activation continued during
      implantation period. The immunoreactivities of p50 and p65 were mainly localized
      in endometrial epithelium, and were weaker in endometrial stroma cells.
      CONCLUSION: NF-kappaB activity is dynamically regulated during the sexual cycle
      as well as during the implantation period in the endometrium, where the
      biochemical interaction between mother and conceptus first occurs.

PMID- 14725563
TI  - Estrogen decreases expression of chemokine receptors, and suppresses chemokine
      bioactivity in murine monocytes.
AB  - PROBLEM: We propose that the ability of estrogen exposure to increase the
      probability of a woman developing breast cancer may be related to decreased
      chemokine activity and suppression of immune surveillance in mammary tissue. The
      present study was conducted to determine whether estrogen could decrease monocyte
      bioactivity through alteration of chemokine receptor expression. METHOD OF STUDY:
      We examined the effect of estrogen and tamoxifen on the expression of the
      chemokine receptors CCR2 and CXCR3 on murine monocytes treated in culture and in
      vivo. Effects of estrogen on chemokine activation of monocytes were also
      evaluated. RESULTS: Estrogen and tamoxifen significantly decreased expression of
      CCR2 and, to a lesser extent, CXCR3 on murine monocytes. Estrogen decreased
      chemotaxis of monocytes towards MCP-1/JE. The chemokines MCP-1/JE and MIP-1alpha
      were unable to evoke increases in intracellular calcium in murine monocytes
      treated with estrogen, alone or in combination with tamoxifen. CONCLUSIONS: Our
      results show that estrogen suppresses the ability of monocytes to respond to
      certain chemokines, suggesting that estrogen exposure might decrease immune
      surveillance in tissues where the action of specific chemokines is involved.

PMID- 14725564
TI  - Tissue eosinophilia in pemphigoid gestationis: association with eotaxin and
      upregulated activation markers on transmigrated eosinophils.
AB  - PROBLEM: We studied chemotactic cytokines and activation of skin-homed
      eosinophils in pemphigoid gestationis, a rare autoimmune bullous disease of late
      pregnancy. METHOD OF STUDY: Eotaxin and interleukin (IL)-5 were analysed in
      patients' blister fluid and serum by enzyme-linked immunosorbent assay. Lesional
      tissue was investigated for eotaxin deposition by immunohistochemistry. Adhesion
      molecules and activation markers on tissue eosinophils were analysed by
      immunofluorescence staining. RESULTS: Eotaxin was elevated in serum of two
      pemphigoid gestationis patients compared with nine healthy pregnant women.
      Blister fluid contained even higher amounts of eotaxin and in addition IL-5.
      Eotaxin was mainly expressed in subepidermal tissue in close proximity to
      eosinophils that expressed high levels of adhesion molecules (CD11b, CD11c, CD18
      and CD49d) and the activation marker HLA-DR. CONCLUSIONS: High local levels of
      eotaxin and IL-5 as present in the blister fluid correspond to the high state of
      activation of the infiltrated eosinophils.

PMID- 14725565
TI  - Therapy with dendritic cells influences the spontaneous resorption rate in the
      CBA/J x DBA/2J mouse model.
AB  - PROBLEM: DBA/2J-mated CBA/J female mice are prone to a high incidence of fetal
      abortions. This fetal wastage can be dramatically reduced by immunizing the
      female mice with BALB/c, but not with DBA/2J spleen cells during early gestation.
      Nevertheless, the underlying mechanisms remain to be elucidated. Recently,
      dendritic cells (DC) have been described at the feto-maternal interface in the
      human uterus. In this work, we studied the effect of adoptive transfer of DC on
      the maintenance of pregnancy in the CBA/J x DBA/2J model. METHODS: Bone marrow
      derived DC were generated from virgin female CBA/J mice (6-8 weeks old). CBA/J
      females were inoculated with DC twice before mating. Four different experimental
      groups were included: (i) no treatment control, (ii) mice injected with culture
      medium [granulocyte-macrophage colony-stimulating factor (GM-CSF)], (iii)
      immunized with DC and (iv) immunized with paternal DBA/2J antigens lisate-pulsed
      DC, n = 5. RESULTS: The control abortion rate was 23.8%, and with GM-CSF alone
      was 17.6%. Following inoculation of syngeneic DC abortion rates were reduced to
      2.2%, but protection was short-lived. Abortion rates with DC pulsed with DBA/2J
      antigens was 5%. Serum of interleukin (IL)-6 levels were lower in the latter two
      groups up to the time of abortion. The kinetics of immunoglobulin G asymmetric
      antibodies synthesis was modified, but there was no correlation between
      asymmetric antibodies production and the lowering of abortions rates. CONCLUSION:
      Syngeneic DC prevented abortions and this was linked to a decrease in IL-6
      levels, but not with levels of asymmetric antibodies.

PMID- 14725566
TI  - Analysis of macrophage presence in murine placenta: influence of age and parity
      status.
AB  - PROBLEM: Beneficial effects of multiparity status have been previously reported
      by different authors. However, this fact has not been fully explained. Taking
      into consideration the influence of the parity status on the in vitro
      asymmetric/protective antibodies and the fact that interleukin-6 (IL-6) is
      involved in the production and immune-regulatory functions of placental
      macrophages, the aim of this work was to compare the placental IL-6 production
      and tissue macrophage presence in mice with different age and parity status.
      METHOD OF STUDY: Three groups of mice (CBA/J x CBA/J) were analyzed: primiparous
      young (PY: 3.0 +/- 0.5 months old), primiparous old (PO: 8.5 +/- 0.5 months old),
      and multiparous old (MO: 8.5 +/- 0.5 months old, with three to four previous
      pregnancies). Macrophage and IL-6 were identified in placental tissue by
      immunohistochemistry employing anti-F4/80 or anti-IL-6 antibodies. IL-6 secretion
      was analyzed in the placental culture supernatants by enzyme-linked immunosorbent
      assay. RESULTS: The results obtained indicate that, despite the level of
      macrophages observed in the PO placentae was higher than in PY ones, their
      expression in MO placentae was very much increased, appearing like a thick layer
      between decidua and trophoblast. However, no significant difference was found
      among the groups in the tissue expression of IL-6 and in IL-6 secreted in vitro.
      CONCLUSIONS: Our data indicate that parity status influences the number of local
      macrophages and might provide evidence that could explain the known beneficial
      effect of multipaternity. We suggest that the number of previous pregnancies
      favor the production of a 'protective' population of macrophages.

PMID- 14725567
TI  - Anti-proliferative effect of mycobacteria, IFN-gamma and TNF-alpha on primary
      cultures derived from endometrial stroma: possible relevance to endometriosis?
AB  - PROBLEM: To assess the effects of mycobacteria and inflammatory cytokines on
      proliferation of endometrial stromal cells. An effect on endometrial stromal cell
      proliferation in vitro may suggest a similar effect on endometriotic cells in
      vivo. METHOD OF STUDY: Primary cultures of endometrial stromal cells were grown
      from female volunteers. Proliferation of cells was assessed by cell counting and
      incorporation of tritiated thymidine after exposure to mycobacteria or
      inflammatory cytokines. RESULTS: When assessed by cell counting, stromal cell
      growth was reduced following treatment with Connaught Bacillus of Calmette and
      Guerin (BCG) and Pasteur BCG: Mycobacterium smegmatis demonstrated a cytotoxic
      effect. Addition of the cytokines interferon (IFN)-gamma or tumour necrosis
      factor (TNF)-alpha at high concentrations led to a reduction in cell growth by 24
      hr in two of three cell lines. A reduction in proliferation was also found when
      assessed by tritiated thymidine incorporation, which was statistically
      significant for Connaught BCG and M. smegmatis. CONCLUSIONS: Endometrial stromal
      cells are susceptible to the anti-proliferative effects of mycobacteria. The BCG
      and other mycobacteria are known immunomodulators in other disease conditions.
      Further work is required to assess whether these in vitro effects might translate
      into a useful therapy for endometriosis.

PMID- 14725568
TI  - Expression of IL-4, IL-8 and IL-18 messenger RNAs in maternal peripheral blood
      and relationships with the HbF-gamma chain mRNA in it.
AB  - PROBLEM: This study was designed to examine immunological changes in maternal
      peripheral blood and the relationship of these changes with the amount of fetal
      cells in the blood. METHOD OF STUDY: The expression of interleukin-4 (IL-4), IL
      8, IL-18 and fetal hemoglobin gamma chain (HbF-gamma chain) messenger RNAs
      (mRNAs) in maternal peripheral blood was measured by a quantitative reverse
      transcription-polymerase chain reaction method. RESULTS: In maternal peripheral
      blood, the expression of IL-4 mRNA was up-regulated from the second gestational
      month (GM) to delivery. The expression of IL-8 and IL-18 mRNAs was down-regulated
      from the third or fourth GM until the eighth or ninth GM, respectively, and both
      increased before the onset of labor, though IL-4 mRNA decreased. The expression
      of IL-8 and IL-18, but not IL-4, mRNAs was correlated with that of HbF-gamma
      chain mRNA. CONCLUSIONS: Immunological interactions between maternal peripheral
      immune cells and fetal cells appear to be related to the onset of labor.

PMID- 14725569
TI  - Relationship between cytokine concentrations (FGF, sICAM-1 and SCF) in serum,
      follicular fluid and ICSI outcome.
AB  - OBJECTIVE: The aim of this study was (i) to investigate the existence of
      fibroblast growth factor (FGF), soluble intracellular adhesion molecule-1 (sICAM
      1), and stem cell factor (SCF) in serum and human follicular fluid (FF) of
      intracytoplasmic sperm injection (ICSI) patients, and (ii) to determine the
      relationship between these parameters and ICSI outcome. MATERIAL AND METHOD:
      Seventy-five patients undergoing controlled ovarian hyperstimulation with human
      menopausal gonadotropin (hMG) after down-regulation with GnRHa were included in
      this study. The concentrations of FGF, SCF, and sICAM-1 were measured by using
      commercially available enzyme-linked immunosorbent assay test kits. RESULTS: The
      FGF, sICAM-1, and SCF concentrations in the serum of women who become pregnant
      (group I) were 8.5 +/- 1.5 pg/mL, 235.8 +/- 81.1 ng/mL, and 597.7 +/- 139.9
      pg/mL, and the corresponding concentrations of women who did not (group II) were
      6.4 +/- 3.6 pg/mL, 230.6 +/- 66.5 ng/mL, and 569.6 +/- 91.4 pg/mL respectively.
      No significant difference was observed between the two investigated groups with
      regard to the number of hMG ampoules administered for controlled ovarian
      hyperstimulation, estradiol concentration on the day of human chorionic
      gonadotropin (hCG) injection, number of retrieved oocytes and fertilization rate.
      CONCLUSION: The concentration of FGF, sICAM-1, and SCF did not differ
      significantly between the two groups in serum or in FF. Besides, the ICSI outcome
      was not related to their concentrations in serum or FF. Therefore, these
      parameters could not be used as a prognostic factor in ICSI program.

PMID- 14725570
TI  - Nerve growth factor and its functional receptor TrkA are up-regulated in murine
      decidual tissue of stress-triggered and substance P-mediated abortion.
AB  - PROBLEM: Stress, elicited by environmental and social conditions, is known to
      affect the homeostasis of the nervous, endocrine and immune systems. In
      pregnancy, perceived stress results in a predomination of inflammatory abortion
      associated Th1 cytokines over immunosuppressive, pregnancy-protective-associated
      Th2 cytokines, putatively via neuropeptide substance P (SP). Nerve growth factor
      (NGF), an important trophic factor for sympathetic neurons, has been implicated
      in the responsiveness of immune-competent cells through its functional receptor,
      tropomyosin receptor kinase (TrkA). Thus, the aim of the present study was to
      identify a cross-talk between distinct neurotrophic and immune mediators in
      pregnancy maintenance. METHOD OF STUDY: Using immune fluorescence, we evaluated
      decidual and placental expression of NGF and TrkA on gestation day (gd) 13.5 in
      the abortion-prone mouse model CBA/J x DBA/2J in (1) CBA/J female control mice;
      (2) CBA/J mice exposed to stress on gd 5.5; and (3) CBA/J mice injected with SP
      on gd 5.5 to mimick stress perception. RESULTS: Stress and SP injection
      significantly increased the abortion rate and up-regulated decidual NGF and TrkA
      expression compared with the control. Stress, but not SP injection down-regulated
      placental NGF, whereas no changes in placental TrkA were observed. CONCLUSION:
      Our data suggest a functional role for NGF in stress-triggered, SP-mediated
      abortion.

PMID- 14725572
TI  - Review article: uninvestigated dyspepsia and non-ulcer dyspepsia-the use of
      endoscopy and the roles of Helicobacter pylori eradication and antisecretory
      therapy.
AB  - Due to its prevalence, impact on quality-of-life and the associated significant
      health resource utilization, dyspepsia is a major healthcare concern. The
      available management strategies for uninvestigated dyspepsia include prompt
      endoscopy, the 'test-and-treat' strategy for Helicobacter pylori, and empiric
      antisecretory therapy. There is consensus that endoscopy should be reserved for
      patients with alarm features (e.g. symptom onset after 45 years of age, recurrent
      vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori
      positive individuals who fail test-and-treat, and those with an inadequate
      response to empiric antisecretory therapy. Factors influencing the decision
      between test-and-treat and empiric antisecretory therapy in uninvestigated
      dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and
      the proportion of ulcers attributable to H. pylori. For uninvestigated dyspepsia
      in patients without alarm features, test-and-treat is the preferred initial
      management method in Europe based on the relatively high prevalence of H.
      pylori/peptic ulcer disease whereas empiric antisecretory therapy is preferred in
      many parts of the United States, where the prevalence of H. pylori/peptic ulcer
      disease is relatively low. In patients with non-ulcer dyspepsia, H. pylori
      eradication and empiric antisecretory therapy result in comparable and small, but
      statistically significant, improvements in dyspepsia. Empiric antisecretory
      therapy is the preferred initial method of managing non-ulcer dyspepsia in Europe
      and the US. The test-and-treat approach would receive increased enthusiasm if H.
      pylori cure is shown to prevent development of gastric cancer in non-ulcer
      dyspepsia patients in a large Western trial.

PMID- 14725573
TI  - Review article: should NSAID/low-dose aspirin takers be tested routinely for H.
      pylori infection and treated if positive? Implications for primary risk of ulcer
      and ulcer relapse after initial healing.
AB  - Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) can each result in gastric or duodenal ulcer(s) and ulcer complications.
      Together, H. pylori infection and NSAIDs account for approximately 90% of peptic
      ulcer disease. In 2003, the results of studies suggest, and guidelines recommend,
      the careful selection of anti-inflammatory drugs - NSAIDs or selective COX-2
      inhibitors (coxibs) based upon patients gastrointestinal history and use of
      aspirin therapy. Testing for, and cure of, H. pylori infection is recommended in
      patients prior to the initiation of NSAID therapy and in those who are currently
      receiving NSAIDs and have a history of dyspepsia, peptic ulcer or ulcer
      complications. For patients who present with peptic ulcer bleeding but require
      NSAIDs long-term, H. pylori eradication therapy should be considered, followed by
      continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless
      of which kind of NSAID (nonselective NSAID /coxib) is being prescribed. Routine
      testing for, and eradication of, H. pylori infection has not been recommended for
      current takers of NSAIDs with no or low risk of complications. The management of
      patients taking low-dose aspirin is complex, but eradication of H. pylori
      infection alone in those with a past history of bleeding does not guarantee
      complete protection and therefore a proton pump inhibitor should also be given.
      The success of eradication therapy should always be confirmed, because of the
      risk of ulcer recurrence and bleeding in H. pylori-infected patients who require
      anti-inflammatory treatments.

PMID- 14725574
TI  - Review article: impact of Helicobacter pylori on society-role for a strategy of
      'search and eradicate'.
AB  - Helicobacter pylori infection is causally related to gastric cancer, a malignancy
      associated with high morbidity and poor prognosis, and to peptic ulcer disease, a
      disease with high morbidity and modest mortality. Theoretically, H. pylori
      eradication is the most practical means of preventing gastric cancer and peptic
      ulcer disease. From a public policy perspective, the current evidence is
      insufficient to assess accurately the magnitude of the benefits of a universal
      'search and treat' approach. Nonetheless, it is possible to identify high-risk
      patients for whom testing for the presence of H. pylori infection, with the
      intention-to-treat infected individuals is currently indicated. This list
      includes patients with ulcers or dyspepsia, first-degree relatives of patients
      with peptic ulcer or gastric cancer, gastric cancer patients after potentially
      curative resection of their gastric cancer, patients in whom long-term acid
      antisecretory therapy or long-term nonsteroidal anti-inflammatory drug therapy
      (including low-dose aspirin) is planned, and finally those who desire testing.
      Population screening among asymptomatic individuals with a high risk of gastric
      cancer, such as Korean- and Japanese-Americans, appears logical, but from a
      public health perspective should be done as a component of controlled
      intervention studies. There are no known H. pylori infections without risk of a
      symptomatic outcome, therefore screening represents a rational strategy for
      cancer prevention. Adoption of such a policy will require carefully balancing the
      costs of the programme with its benefits.

PMID- 14725575
TI  - Review article: epidemiology and management of gastro-oesophageal reflux in
      children.
AB  - The management of gastro-oesophageal reflux disease (GERD) continues to garner
      vast amounts of attention among physicians who care for adults. However, there is
      an increasing awareness of the fact that this disease, as well as several other
      lifelong digestive diseases (i.e. Crohn's disease) may actually have their
      origins in childhood. Paediatric gastro-oesophageal reflux (GER) is likely to
      share a similar pathophysiology to adult GER, and mounting evidence from
      published preliminary data suggests a genetic susceptibility to GERD. However,
      further studies will be necessary to confirm this hypothesis. In children, GER
      has a distinct presentation from that in adults, with the diagnostic work-up
      based upon the patient's age as well as their presenting signs and symptoms. Like
      their adult counterparts, the early detection and treatment of GER in children
      may result in a better long-term outcome, improved quality-of-life, and a
      reduction in overall healthcare burden. While the treatment of GER in infants
      tends to be conservative (i.e. positioning during feeding, smaller feedings), its
      management in older children parallels that of adults and includes lifestyle
      changes and pharmacological therapy. However, with persistent symptoms, acid
      suppression is the mainstay of GERD management in both children and adults.
      Several studies in children have verified that acid suppression with a proton
      pump inhibitor is superior to histamine-2 receptor antagonists. Among the proton
      pump inhibitors, both lansoprazole and omeprazole have been the subject of
      published adult and paediatric studies demonstrating their short and long-term
      safety, in addition to their efficacy in a variety of oesophageal and supra
      oesophageal GERD related conditions. These two proton pump inhibitors are
      manufactured as capsules containing enteric-coated granules that can be emptied
      into soft foods or liquids without compromising their pharmacological effects or
      pharmacokinetic properties. Lansoprazole is also available as a strawberry
      flavoured suspension that is acceptable to children and as an oral disintegrating
      tablet.

PMID- 14725576
TI  - Review article: approaches to endoscopic-negative reflux disease: part of the
      GERD spectrum or a unique acid-related disorder?
AB  - Endoscopic-negative reflux disease (ENRD) is the most common presentation of
      gastro-oesophageal reflux disease (GERD)-affecting up to 70% of these
      individuals. In the last three decades therapeutic studies have focused solely on
      the treatment of patients with erosive oesophagitis. However, more recent studies
      have shifted our attention to defining, understanding and treating those with
      ENRD. GERD has traditionally been approached as a spectrum with ENRD at the mild
      end and complicated GERD (i.e. patients with erosive oesophagitis, stricture and
      Barrett's oesophagus) being at the other end, suggesting that patients' disease
      may progress over time along the spectrum. Current data indicate that ENRD should
      be approached as a unique entity rather than a part of the GERD spectrum and that
      over time only a few patients with ENRD will develop GERD-related complications.
      Patients with ENRD are a heterogenous group of patients with different
      aetiologies for their heartburn symptoms, including motor events, reflux of
      acidic or nonacidic gastric contents, minute changes in intraesophageal pH (pH <
      4), mucosal hypersensitivity, and emotional or psychological abnormalities. By
      dropping the spectrum concept, which emphasizes oesophageal mucosal injury, we
      can focus our attention on the specific mechanisms that lead to symptom
      generation in each of the three unique groups of GERD (ENRD, erosive oesophagitis
      and Barrett's oesophagus) and on the specific therapeutic modalities that benefit
      each of these individual groups. Acid suppressive therapy with proton pump
      inhibitors is highly effective in healing erosions and controlling symptoms in
      those with erosive oesophagitis. In those with ENRD the resolution or control of
      heartburn with proton pump inhibitor therapy is greater than that with placebo or
      H2 receptor antagonist, but not as consistent nor as impressive as the results
      observed in studies of patients with erosive oesophagitis. By considering the
      mechanisms involved in ENRD symptom generation, future studies that include high
      dose proton pump inhibitors, promotility agents (alone or in combination with
      proton pump inhibitors), transient lower oesophageal sphincter reducers, or pain
      modulators (e.g. tricyclic antidepressant agents) may prove beneficial.

PMID- 14725577
TI  - Review article: approaches to the long-term management of adults with GERD-proton
      pump inhibitor therapy, laparoscopic fundoplication or endoscopic therapy?
AB  - The goals of gastro-oesophageal reflux disease (GERD) treatment are to control
      symptoms, heal the injured oesophageal mucosa, and prevent complications.
      Pharmacological therapy is effective in producing acute symptom relief and
      mucosal healing, as well as the long-term maintenance of remission. Proton pump
      inhibitors are the mainstay of GERD therapy. However, the need for daily
      administration, failure to provide complete symptom relief and costs of these
      agents may limit their use in some patients, prompting a consideration of
      alternative treatment strategies. Laparoscopic fundoplication may achieve symptom
      relief and healing of the oesophagitis in these individuals, but its
      invasiveness, cost and inherent surgical risks have created an interest in
      endoscopic therapies for GERD, with several emerging during the past few years.
      These interventions may either be viewed as an alternative therapy or as 'bridge'
      therapy, with patients still choosing to be treated with acid anti-secretory
      drugs or fundoplication if the endoscopic procedure fails to provide adequate
      symptom relief or if symptoms recur. Patient selection is critical for the
      success of fundoplication as well as endoscopic procedures, with ideal candidates
      being those with well-established endoscopically documented GERD, abnormal pH
      monitoring, normal oesophageal motility studies, and who have experienced at
      least partial symptom relief with proton pump inhibitor therapy. Hiatal hernia is
      not a contra-indication to fundoplication, while endoscopic intervention is best
      suited for those with a hiatal hernia of less than 3 cm in length. The long-term
      efficacy, cost-effectiveness, and impact of endoscopic procedures on extra
      oesophageal manifestations of GERD and risk for GERD-related complications has
      not been determined.

PMID- 14725578
TI  - Review article: supra-oesophageal manifestations of gastro-oesophageal reflux
      disease.
AB  - Supra-oesophageal manifestations of gastro-oesophageal reflux disease (GERD) are
      common and often under-appreciated, in part due to the absence of classic
      symptoms of heartburn and regurgitation. Patients with supra-oesophageal
      manifestations of GERD may report symptoms involving the pulmonary,
      otolaryngologic or pharyngeal systems. Endoscopy is often negative and therefore
      of limited diagnostic value in these patients, and while laryngoscopy and 24 h
      dual-channel intra-oesophageal pH-metry may have greater yields they are costly,
      invasive and time-consuming. Therefore, a trial of proton pump inhibitor therapy
      is now widely considered a first-line diagnostic test in those with suspected
      GERD-induced supra-oesophageal symptoms. The dose as well as duration of the
      proton pump inhibitor trial is dependent upon a patient's presenting symptoms.
      For example, GERD-related non-cardiac chest pain may be relieved with a short
      term (e.g. 1 week) treatment with standard doses of a proton pump inhibitor. The
      use of high-dose twice daily proton pump inhibitor therapy for an extended period
      (e.g. 2-3 months) may be required before any discernible improvement in pulmonary
      symptoms or pharyngo-laryngitis is noted. Patients who do not experience symptom
      improvement following a proton pump inhibitor trial may require further
      diagnostic evaluations including 24 h oesophageal pH studies, while on acid anti
      secretory therapy, to establish the absence of persistent acid reflux. The role
      of anti-reflux surgical or endoscopic interventions in those with supra
      oesophageal manifestations of GERD remains to be established.

PMID- 14725579
TI  - Review article: screening and surveillance of Barrett's oesophagus: what is a
      cost-effective framework?
AB  - There is a strong association between symptomatic gastro-oesophageal reflux and
      oesophageal adenocarcinoma. With this in mind, the American College of
      Gastroenterology has recently revised its practice guidelines for the screening
      of patients with chronic gastro-oesophageal reflux disease (GERD) to identify
      those at risk of oesophageal adenocarcinoma, and recommends surveillance to
      identify curable oesophageal neoplasms in patients with established Barrett's
      oesophagus. Patients with chronic GERD symptoms, particularly those aged over 50
      years, should undergo upper endoscopy. Patients found to have Barrett's
      oesophagus should be treated with acid suppression for GERD symptoms and then
      undergo regular surveillance endoscopy. Surveillance endoscopy every 3 years is
      recommended for those without dysplasia. For patients with verified low-grade
      dysplasia, yearly surveillance endoscopy is recommended. For those with focal
      high-grade dysplasia (defined as high-grade dysplastic changes involving fewer
      than five crypts), the condition may be followed with endoscopic surveillance
      performed at 3-month intervals. If there is verified, multifocal high-grade
      dysplasia, intervention (e.g. oesophagectomy) may be considered. Both
      observational and computer models suggest a benefit associated with screening and
      surveillance. Endoscopic screening and surveillance for Barrett's oesophagus
      compares favourably with mammography for the detection of breast cancer and other
      accepted medical practices.

PMID- 14725580
TI  - Review article: approaches to Barrett's oesophagus treatment-the role of proton
      pump inhibitors and other interventions.
AB  - Despite implementation of screening and surveillance strategies, a significantly
      large number of patients with Barrett's oesophagus remain undiagnosed. In those
      who are identified, the management options include acid reduction therapies with
      proton pump inhibitors or anti-reflux surgery. Endoscopic ablative therapies have
      also been attempted. In addition to having inherent procedure-related risks with
      ablative therapies, these alternatives may be limited by high rates of failure,
      need for continued acid suppressive therapy, metaplasia persistence under
      otherwise normal appearing tissue, need for procedural expertise, and continued
      risk for adenocarcinoma development. Therefore, a widely applicable
      chemoprevention strategy that cost-effectively reduces the rate of progression
      from oesophagitis to adenocarcinoma in high-risk patients and perhaps those at
      lower rates of risk is highly desirable. The AspECT trial currently underway is
      seeking to determine the effects of high- and low-dose proton pump inhibitor
      therapy with and without low-dose aspirin as Barrett's oesophagus
      chemoprevention.

PMID- 14725581
TI  - Review article: appropriate use of proton pump inhibitors with traditional
      nonsteroidal anti-inflammatory drugs and COX-2 selective inhibitors.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used
      classes of medications in the USA, annually accounting for over 100 million
      prescriptions. Gastrointestinal complications associated with NSAIDs are common,
      and result in a substantial amount of morbidity and mortality, despite the advent
      of the cyclooxygenase-2 selective inhibitors or 'coxibs'. Emerging clinical and
      economic data suggest that, depending on the baseline risk to patients, the use
      of a traditional NSAID alone or in combination with a proton pump inhibitor are
      effective and well tolerated alternatives to coxibs. The optimal therapeutic
      strategy for NSAID selection and use of co-therapy should be guided by a
      consideration of each patient's risk of having an adverse event arising from the
      NSAID. Patients at the highest risk for gastrointestinal complications with
      traditional NSAIDs are those with a history of an ulcer or ulcer complication,
      those of advanced age (greater than 65 years), and those receiving concurrent
      aspirin, anticoagulants or corticosteroid therapy. Proton pump inhibitor co
      therapy is highly effective in reducing NSAID-related dyspeptic symptoms, healing
      the injured mucosa even in those who continue to ingest NSAIDs, and preventing
      gastrointestinal complications. In addition to their selective use in patients
      who experience NSAID-related dyspepsia and other symptoms, proton pump inhibitor
      co-therapy should be considered in those at high risk (with coxib or traditional
      NSAID therapy) and is necessary in high-risk patients receiving aspirin, with or
      without NSAID therapy.

PMID- 14725582
TI  - Review article: management of peptic ulcer bleeding-the roles of proton pump
      inhibitors and Helicobacter pylori eradication.
AB  - Peptic ulcer bleeding is associated with substantial morbidity and mortality. The
      goals of management are to control any active bleeding and prevent re-bleeding
      and then to heal the ulcer and prevent its recurrence. Initial management
      strategies are guided by the patient's clinical condition and endoscopic
      findings. Thus, treatment may consist of endoscopic and medical therapy and,
      sometimes, surgery. Control of acid secretion, preferably with proton pump
      inhibitor therapy in the initial management continues to evolve; it has also been
      used as both an adjunct to endoscopic therapy and as primary treatment. These
      agents have been found to be effective in some trials in the reduction of re
      bleeding and the need for surgery, although there is no clear benefit
      demonstrated for overall mortality. Proton pump inhibitors have been administered
      either intravenously or orally in different trials. The long-term management of
      patients with peptic ulcer, after the initial bleeding episode, should include
      patient stratification based upon risk factors for ulcer recurrence (i.e.
      Helicobacter pylori infection, use of aspirin or nonsteroidal anti-inflammatory
      drugs). Elimination or modification of these risk factors reduces the risk of
      ulcer recurrence and, hence, of recurrent ulcer bleeding.

PMID- 14725583
TI  - Review article: balancing the ideal versus the practical-considerations of
      colorectal cancer prevention and screening.
AB  - Colorectal cancer is responsible for over 500 000 deaths annually world-wide.
      Death from colorectal cancer is preventable, primarily through early diagnosis of
      disease that has not metastasized. The disease itself may be prevented by the
      detection and removal of colorectal adenomas, from which more than 95% of
      colorectal cancers arise. Currently there are several screening methods for the
      disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and
      colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA
      testing. While direct and indirect evidence support the efficacy of these tests
      they differ from each other in their sensitivity, specificity, cost, and safety.
      Various professional organizations in different geographical regions of the world
      have published recommendations on which screening methods to use and when in
      patients at average- or high-risk. The challenge in reducing the incidence and
      mortality of this disease lies in increasing accessibility to and compliance with
      screening and delivery within a quality assured programme.

PMID- 14725584
TI  - Chairmen's summary: dichotomies and directions in acid-related disorders.
AB  - Presentations by international experts from old and new worlds bordering the
      Atlantic Ocean revealed surprising similarities with respect to the diagnosis and
      management of patients with upper gastrointestinal disorders. It was agreed that
      Helicobacter pylori infection continues to play a key role in gastroduodenal
      disease and has a great impact on clinical management. However, testing and
      treatment strategies vary in patients affected by functional dyspepsia and those
      receiving nonsteroidal anti-inflammatory drug (NSAID) therapy including aspirin.
      Among patients with gastro-oesophageal reflux disease (GERD), it was clear that
      we need to re-evaluate the validity of the classical concept of GERD as a
      progressive spectrum and instead focus on the pathophysiologic mechanisms
      responsible for producing the common symptom of heartburn and complications that
      occur in the three principle subsets of GERD patients: those with endoscopic
      negative reflux disease, erosive oesophagitis and Barrett's oesophagus. In
      addition, we need to be increasingly aware of the concept of extra-oesophageal
      manifestations of gastro-oesophageal reflux and the fact that GERD in adults
      often originates in childhood. In all these gastrointestinal disorders, proton
      pump inhibitor therapy has become the common thread either as a diagnostic tool
      or an effective short-term or long-term management strategy.

PMID- 14725585
TI  - Gastrointestinal disorders are among the most common disorders encountered in the
      United States and Europe.

PMID- 14725586
TI  - The clinical effects of lithium discontinuation: the debate continues.

PMID- 14725587
TI  - Psychoeducation and cognitive-behavioral therapy in bipolar disorder: an update.
AB  - OBJECTIVE: To review the available literature on psychoeducation and cognitive
      behavioral therapy (CBT) in bipolar disorder (BD) and to give an integral view of
      these therapies. METHOD: Studies were identified through Medline searches in
      English language publications between 1971 and 2003. This was supplemented by a
      hand search and the inclusion of selected descriptive articles on good clinical
      practice. RESULTS: A number of studies demonstrate that psychoeducation enhances
      adherence to treatment, and one finds that it improves outcome in BD. Other
      studies find that CBT diminishes depressive symptoms and improves quality of life
      in BD. Occasionally some adverse effects may occur with psychotherapy and,
      although they are sporadic, should not be overlooked. CONCLUSION: When combined
      with pharmacological treatment, psychoeducation helps to improve adherence.
      Training in the identification of early manic symptoms helps to improve outcomes
      and decreases the number of manic relapses in BD.

PMID- 14725588
TI  - Relapse into mania or depression following lithium discontinuation: a 7-year
      follow-up.
AB  - OBJECTIVE: We aimed to assess whether outcome followed a worse course after acute
      lithium withdrawal. METHOD: Data were acquired by review of the clinical records
      on 14 cases and 28 controls matched for age, gender and time on lithium for about
      7 years following discontinuation. RESULTS: Significant differences were found
      between cases and controls. Cases experienced more episodes of depression and
      total affective relapse. The log-rank test revealed a significantly lower
      survival probability in cases than controls (P < 0.0009). However, the increased
      risk of recurrence was largely confined to the interval immediately after lithium
      discontinuation. CONCLUSION: These results confirm that acute discontinuation of
      lithium leads to a high immediate relapse rate. Most of the excess morbidity over
      7 years appears to be attributable to the first episode following
      discontinuation. Outcome was not worsened by discontinuation.

PMID- 14725589
TI  - Prevalence of major depression and stress indicators in the Danish general
      population.
AB  - OBJECTIVE: To estimate the prevalence rate of major depression in the Danish
      general population by using the Major Depression Inventory (MDI), a validated
      self-rating scale fulfilling the symptomatic criteria in DSM-IV and ICD-10 for a
      depressive episode. METHOD: A booklet containing the MDI and a number of
      questions on psychosocial factors was sent to 2040 randomly selected Danish
      citizens. The sample was age- and gender-stratified. Mean MDI scores were
      calculated. Logistic regression analysis was used in order to produce a model for
      the influence of psychosocial factors. RESULTS: The response rate was 60%. The
      point prevalence of major depression was 3.3%. Among the tested predictors of
      depression were sociodemographic variables, alcohol and smoking habit, bodily
      pain, somatic diseases and traumatic life events. For a traumatic event in
      personal life over the past year odds ratio was 6.4 [2.7; 15.5], for
      overconsumption of alcohol odds ratio was 3.2 [1.5; 6.8]. While the gender
      difference in major depression rate was not found statistically significant, a
      significant (P < 0.05) gender difference of male to female of 1 : 2 was found
      when including minor depression. Of people identified as having a major
      depression only 13% were currently treated by a medical doctor. CONCLUSION: Major
      depression has a high prevalence in the Danish general population and seems to be
      undertreated. The gender difference was only found statistically significant when
      including minor depression, indicating that the female predominance is less
      pronounced in the more severe depression states.

PMID- 14725590
TI  - Persistent social dysfunction in anxious and depressed patients with personality
      disorder.
AB  - OBJECTIVE: To determine the long-term social function of psychiatric patients
      with anxiety and depressive disorders and to relate this to personality status
      and other factors. METHOD: A cohort of 210 patients (mean age 35 years) with
      dysthymic disorder, generalized anxiety disorder or panic disorder diagnosed
      using a structured interview (SCID) were assessed at baseline for personality
      status using the Personality Assessment Schedule (PAS) and ratings of anxiety and
      depression. Exactly 12 years later social function was assessed using the Social
      Functioning Questionnaire (SFQ) and personality reassessed with the PAS by a
      rater blind to initial personality status. Individual social function items were
      examined in those with and without personality disorders. RESULTS: Social
      function was significantly better in those with little or no baseline personality
      disturbance (P < 0.001) and the domains of close relationships, stress in
      completing tasks, use of spare time and family relationships showed the largest
      personality differences. A multiple linear regression model showed that self
      rated depression scores, single marital status and personality status were the
      main baseline variables predicting social function at 12 years. CONCLUSION:
      Although personality characteristics may change over time social dysfunction
      persists and persistent social dysfunction in mental state disorders may be a
      strong indicator of personality disturbance rather than an indicator of treatment
      resistance.

PMID- 14725591
TI  - Time patterns and seasonal mismatch in suicide.
AB  - OBJECTIVE: Physical time-givers may have a modifying effect on the time patterns
      of death from suicide. METHOD: Data on a total of 1397 suicides in Finland over a
      year were collected using the method of psychological autopsy. We linked
      versatile information on each individual to meteorological data adjusted for
      local weather conditions, and to the universal astronomic data. RESULTS: The
      number of suicides with seasonal mismatch was greater than the expected in the
      northernmost region of the country (P = 0.03). The northern location was the most
      significant predictor of such suicides (P = 0.001). They were associated with the
      changes in ambient temperature during the preceding day (P < 0.00001), the
      changes to colder preceding suicides in the spring. CONCLUSION: Our findings show
      that mismatch between the changes in ambient temperature and those in the length
      of day may precede death from suicide in some individuals.

PMID- 14725592
TI  - Suicidal behaviour in early psychosis.
AB  - OBJECTIVE: This was to determine the prevalence of suicidal behaviours prior to
      and during the first year of treatment in a comprehensive early psychosis program
      (EPP) and to identify predictors of suicidal behaviour. METHOD: In a cohort study
      of 238 subjects, patients were assessed at initial presentation to an EPP and 1
      year later. Measures included a range of demographic variables, suicide attempts,
      depression, positive and negative symptoms, social functioning and substance
      misuse. RESULTS: Although 15.1% attempted suicide prior to program entry, only
      2.9% made an attempt in the year after program entry and 0.4% completed suicide.
      No further attempts were seen in those with previous parasuicide. These rates are
      lower than other published rates for first-episode patients. CONCLUSION: It is
      possible that specifically designed first-episode programs can reduce the
      suicidal behaviour in this high-risk population. The low prevalence of attempted
      suicide makes modeling predictors difficult.

PMID- 14725593
TI  - Relationship of childhood trauma to age of first suicide attempt and number of
      attempts in substance dependent patients.
AB  - OBJECTIVE: To examine whether childhood trauma effect the age of first attempting
      suicide and the number of attempts. METHOD: One thousand twelve hundred and
      eighty substance dependent patients were interviewed about whether or not they
      had ever attempted suicide, the age of first attempt and the number of attempts.
      Patients completed the Childhood Trauma Questionnaire - 34 item version. RESULTS:
      Five hundred and thirty-eight patients (42%) had attempted suicide. Significantly
      more of the patients who had attempted suicide were female. Patients who had made
      three or more attempts had significantly higher childhood trauma scores than
      patients who had made two attempts, who had higher scores than patients who had
      made one attempt, who had higher scores than patients who had never attempted.
      Patients who first attempted suicide before the age of 20 years had significantly
      higher childhood trauma scores than patients who first attempted after 20 years
      of age. CONCLUSION: Childhood trauma may be a determinant of the age of onset of
      suicidal behavior and of the number of suicide attempts.

PMID- 14725594
TI  - Lower activities of serum peptidases predict higher depressive and anxiety levels
      following interferon-alpha-based immunotherapy in patients with hepatitis C.
AB  - OBJECTIVE: There is evidence that in patients with chronic hepatitis C,
      immunotherapy with interferon-alpha (IFN alpha) may induce depression. A lowered
      activity of peptidases, such as prolylendopeptidase (PEP) and dipeptidyl
      peptidase IV (DPP IV), occurs in depression. This study examines whether lowered
      serum PEP or DPP IV activity before starting IFN alpha-based immunotherapy
      predicts the increase in depressive symptoms during immunotherapy. METHOD: Serum
      PEP and DPP IV activities are measured in patients with hepatitis C before and 2,
      4 and 16 weeks after starting IFN alpha-based immunotherapy. The Montgomery
      Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM
      A) are completed. RESULTS: Patients with lower baseline PEP or DPP IV had
      significantly higher MADRS and HAM-A scores both at baseline and during
      immunotherapy. Patients with lower baseline DPP IV had significantly higher
      increases in the MADRS following IFN alpha treatment. CONCLUSION: Lower baseline
      PEP and DPP IV predict higher depressive and anxiety ratings during IFN alpha
      based immunotherapy.

PMID- 14725595
TI  - The effect of previous psychiatric history on the cost of care: a comparison of
      various regression models.
AB  - OBJECTIVE: Many studies conducted in Europe have reported high variance of costs
      estimated at the individual level. The objectives of the present study were to
      estimate costs of patients and to evaluate the performance of various regression
      models. METHOD: All patients who in the period 1992-1995 had at least one contact
      with the psychiatric services in South Verona were included in the study and were
      followed for 1 year after the index contact (n = 1725). Four different groups,
      classified on the basis of their previous services utilization, were analysed.
      RESULTS: First-ever patients and patients with a new episode of care after 3
      years were less costly than patients with an ongoing episode of care and patients
      having a new episode, after an interval between 3 months and 3 years. CONCLUSION:
      The regression models allow us to predict cost for a patient with a given set of
      characteristics. Great care in the interpretation of the values of the individual
      coefficients should be taken in order to have a broader understanding of the
      expenditure dynamic.

PMID- 14725596
TI  - Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP
      CIT/SPECT study.
AB  - OBJECTIVE: To investigate dopamine transporter binding in Gilles de la Tourette
      syndrome (GTS) with SPECT and [123I]FP-CIT. METHOD: Ten neuroleptic naive/free
      patients with GTS, and 10 age- and gender-matched normal volunteers were studied.
      Subjects were clinically evaluated. GTS severity and affective symptoms were
      measured and the presence of GTS-related behaviours were recorded. RESULTS: The
      GTS group showed significantly higher binding in both caudate and putamen nuclei
      than the controls. No associations were found between striatal binding ratios and
      measures of affect or GTS-related behaviours. CONCLUSION: Patients with GTS show
      higher striatal binding of FP-CIT to the striatum in comparison with age- and
      gender-matched control subjects, indicating that dopamine transporter
      abnormalities are involved in the pathophysiology of GTS. These abnormalities
      appear to be distributed across both caudate and putamen.

PMID- 14725597
TI  - Chronic but not resistant mania: a case report.
AB  - OBJECTIVE: There are many nuances of elevated mood states. At times, it becomes
      very difficult to diagnose a case of mania because of personality style of the
      patient superimposed on a cyclothymic or hyperthymic temperament. Such cases may
      become chronic if timely intervention is not received. We describe a case of
      chronic mania of 48 years of duration. METHOD: A case report. RESULTS: A 65-year
      old male was admitted with history of mania for around five decades. The illness
      commenced at prepubertal age and was continuous without any residual symptoms of
      note. During the course of illness, he got involved in many devastating socio
      politico-legal complications. He showed good response to treatment and is
      currently maintained well without medication. In this case we also described some
      psychosocial features that may have been responsible for the chronicity of the
      illness. CONCLUSION: We highlighted the need for correctly identifying chronic
      mania, early intervention and increasing treatment awareness. This case was not
      treatment resistant, suggesting that chronicity per se should not denote poor
      outcome.

PMID- 14725599
TI  - Do olfactory reference syndrome and jiko-shu-kyofu (a subtype of taijin-kyofu)
      share a common entity?
AB  - OBJECTIVE: Olfactory reference syndrome (ORS) in the Western literature is
      characterized as preoccupation with the idea that the body emits a foul odor.
      Japanese patients with a feature similar to ORS have long been recognized as jiko
      shu-kyofu, which is believed to be a culture-bound syndrome and specific to
      Japan. The aim of the study was to clarify the relationship between the two
      separate syndromes that had independently been recognized in culturally different
      settings. METHOD: The phenomenology and treatment of seven patients with jiko-shu
      kyofu were described. A feature of jiko-shu-kyofu was then compared with that of
      ORS. RESULTS: In our cases, clinical characteristics of jiko-shu-kyofu such as
      symptomatology, insight, and pharmacotherapy response were found identical to
      those of ORS except for the onset at relatively younger ages. CONCLUSION: Jiko
      shu-kyofu and ORS may share a common clinical entity, hence the former is not a
      culturally distinctive disorder.

PMID- 14725601
TI  - Behavioral management of antipsychotic-induced weight gain.

PMID- 14725603
TI  - Latency and outcome of prophylaxis in bipolar disorder: role of severity as a
      confounding variable?

PMID- 14725609
TI  - Vasoactive peptides, their receptors and drug development.
AB  - Vasoactive peptides with vasoconstrictor properties play an important role in
      many physiological and pathological conditions. The peptides act via specific
      receptors, most of them belonging to the group of seven transmembrane G-protein
      coupled receptors. These receptors have become important targets for drugs
      developed to inhibit vasoconstrictor actions. Alternatively, compounds which
      inhibit enzymes generating vasoactive peptides have also been demonstrated to
      represent valuable therapeutic tools. This review will first describe the
      properties and distribution of two very potent vasoconstrictors, angiotensin II
      and endothelin. It will further focus on their receptors and on new drugs, which
      act as antagonists for these receptors. In addition, the properties of indirectly
      acting drugs like angiotensin-converting enzyme inhibitors and--in analogy-
      endothelin-converting enzyme inhibitors will be presented.

PMID- 14725610
TI  - Effect of caffeine-containing versus decaffeinated coffee on serum clozapine
      concentrations in hospitalised patients.
AB  - Clozapine and caffeine are metabolised mainly by the cytochrome P4501A2 (CYP1A2)
      enzyme. Studies suggest that caffeine in coffee inhibits clozapine metabolism and
      increases serum clozapine concentrations. Our objective was to study whether
      coffee in the amounts usually consumed has an effect on steady-state serum
      clozapine concentrations. A randomised placebo-controlled cross-over design with
      two phases was used. Twelve hospitalised clozapine-using patients volunteered in
      the study where, after one-week run-in period, either caffeine-containing or
      decaffeinated instant coffee was available ad libitum for seven days. Serum
      concentrations of clozapine, N-desmethylclozapine, clozapine-N-oxide, caffeine,
      paraxanthine and C-reactive protein were measured after run-in period and on days
      4 and 8 of the following study phases. Two patients were excluded from the
      statistical analysis because of non-compliance based on serum caffeine and
      paraxanthine determinations. In six fully compliant patients caffeine-containing
      coffee increased the mean serum trough concentration of clozapine by 26% (non
      significant (NS), 95% CI -3% to +54%, P=0.07), N-desmethylclozapine by 6% (95% CI
      1% to 12%, P=0.03), and clozapine-N-oxide by 7% (NS, 95% CI -6% to +20%, P=0.22).
      The ratio of N-desmethylclozapine/clozapine decreased by 13% (NS, 95% CI -1% to
      +27%, P=0.06) and that of clozapine-N-oxide/clozapine by 7% (NS, 95% CI -5% to
      +17%, P=0.19). In the analysis of combined data (including day 4 data of the four
      patients compliant up to that point) serum trough concentration of clozapine was
      20% (95% CI 3% to 37% to P=0.03) higher, and that of N-desmethylclozapine 7% (95%
      CI 2% to 13%, P=0.02) higher during the caffeine phase than during the
      decaffeinated phase. We conclude that the effect of instant coffee drinking on
      serum clozapine concentrations is of minor clinical relevance in most of the
      patients, but some individuals may be more sensitive to this interaction due e.g.
      to genetic factors. The increase in serum clozapine concentration was most likely
      due to the inhibition of the CYP1A2 enzyme by caffeine.

PMID- 14725611
TI  - Mechanism of acetaminophen-induced apoptosis in cultured cells: roles of caspase
      3, DNA fragmentation factor, and the Ca2+ and Mg2+ endonuclease DNAS1L3.
AB  - We have recently shown that acetaminophen induces many of the apoptotic traits in
      hepatoma cells and lymphocytes (Boulares et al. (2002d). In an effort to further
      investigate the mechanism by which non-metabolized acetaminophen induces
      apoptosis, we have now examined the roles of caspase-3, the DNA fragmentation
      factor, and the poly(ADP-ribose) polymerase-1-regulated Ca2+ and Mg2+-dependent
      endonuclease DNAS1L3 in the induction of such death process. This was achieved
      with the use of MCF-7 cells, a caspase-3-deficient breast adenocarcinoma cell
      line, thymocytes isolated from DFF45 (the inhibitory and chaperone subunit of the
      DNA fragmentation factor subunit, DFF40) deficient mice, and HeLa cells, a
      DNAS1L3-deficient cervical carcinoma cell line. MCF-7 exhibited a marked
      resistance to acetaminophen treatment. Ectopic expression of human caspase-3
      significantly potentiated the cytotoxic effect of acetaminophen and promoted the
      release of cytochrome c into the cytosol of treated cells suggesting a direct
      role for caspase-3 in acetaminophen-induced apoptosis. Expression and cleavage of
      DFF45 were required but not sufficient for acetaminophen-induced internucleosomal
      DNA fragmentation. DFF45 gene knockout rendered thymocytes resistant against
      acetaminophen-induced generation of both large and internucleosomal DNA
      fragments. The treatment of HeLa cells with acetaminophen resulted in
      internuclesomal DNA fragmentation only after transfection of these cells with a
      plasmid encoding the DNAS1L3 gene suggesting that this endonuclease is required
      for acetaminophen-induced internucleosomal DNA fragmentation. DNAS1L3 expression
      potentiated the cytotoxic effect of acetaminophen in HeLa cells suggesting an
      active role in the death process induced by this drug. Altogether, these results
      demonstrate the specific roles of caspase-3, DNA fragmentation factor, and
      DNAS1L3 in the process of acetaminophen-induced apoptosis in cultured cells.

PMID- 14725612
TI  - The citrus-derived flavonoid naringenin exerts uterotrophic effects in female
      mice at human relevant doses.
AB  - Gavage administration of the citrus flavonoid naringenin, 3',4,5,7
      tetrahydroxyflavanon for 4 consecutive days, to immature female mice (postnatal
      day 17-20) at 4 or 100 mg/kg b.wt. significantly increased uterine weights 3 and
      4 times, respectively. Analysis of uterine oestrogen receptor alpha revealed that
      naringenin significantly increased the cytosolic concentration of oestrogen
      receptor alpha, whereas in nuclei the oestrogen receptor alpha concentration was
      significantly decreased as compared to the solvent control. This was in contrast
      to the positive control 17 beta-oestradiolacetate which acted as a true oestrogen
      by increasing the concentration of both total and nuclear oestrogen receptor
      alpha. Both naringenin and 17 beta-oestradiolacetate, however, significantly,
      induced nuclear oestrogen receptor alpha in the liver, suggesting a tissue
      specific effect of naringenin on oestrogen receptor alpha distribution. In order
      to investigate the tissue levels at which the uterotrophic effect was observed,
      the distribution of an oral dose of tritiated naringenin (4 mg/kg) was
      investigated in 3-week-old female mice. The radioactivity content (ng naringenin
      equivalents/g tissue) was found to be highest in the gastrointestinal-tract,
      followed by the kidneys and liver. Uterus and ovaries were also found to contain
      relatively high and approximately equal amounts of naringenin. The concentration
      of naringenin in uterus and ovaries was found to be ten times higher as compared
      to the mammary tissue. The urinary excretion of more than 25% of the administered
      dose, within 8 hr after dosing indicated that naringenin is absorbed extensively
      in mice. The plasma concentration of 0.5 microM found in the present study is
      similar to the peak plasma concentration of naringenin (0.6 microM) observed in
      man following ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This
      could be taken to suggests that ingestion of orange juice and other citrus fruits
      and juices may give rise to sufficiently high tissue levels of naringenin in man
      to exert a biological effect.

PMID- 14725613
TI  - Effect of endothelin antagonism on contractility, intracellular calcium
      regulation and calcium regulatory protein expression in right ventricular
      hypertrophy of the rat.
AB  - We have documented the effects of long-term endothelin receptor antagonism on
      intracellular Ca2+ regulation and Ca2+ regulatory protein expression in rat
      hearts with right ventricular hypertrophy without signs of heart failure. Rats
      were given either a single injection of monocrotaline (50 mg/kg, n=9) resulting
      in pulmonary hypertension-induced myocardial hypertrophy, or monocrotaline
      followed by daily administration of the endothelin subtype-A receptor antagonist
      2-benzo(1,3)dioxol-5-yl-3-benzyl-4-(4-methoxy-phenyl-)-4-oxobut-2-enoate-Na (PD
      155080, 50 mg/kg) over 9 weeks (n=8). Hearts from saline-injected rats served as
      controls (n=9). Monocrotaline-treated animals developed marked right-sided
      hypertrophy without fibrosis as evident from hydroxyproline measurements,
      systolic contractility was increased, fully compensating for the increased
      afterload, but diastolic function was impaired as evident from protracted
      relaxation and slowed diastolic intracellular Ca2+ handling (measured by aequorin
      bioluminescence). In hypertrophic hearts, quantitative immunoblotting analyses
      showed increased levels both of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)
      and phosphorylated phospholamban, along with decreased levels of total
      phospholamban, which is in line with strengthened right ventricular systolic
      function. PD 155080 reversed abnormalities in Ca2+ handling, although SERCA and
      phospholamban protein levels were not altered (P=not significant versus
      monocrotaline group). Thus, endothelin-A receptor antagonism attenuates right
      ventricular remodeling and improves myocardial Ca2+ handling, but has no
      discernable effect on elevated expression of SERCA and phospholamban observed in
      hypertrophic hearts. These data indicate that the hypotensive action of PD 155080
      is independent of its effects, if any, on SERCA and its regulation.

PMID- 14725614
TI  - Effects of gamma-butyrobetaine and mildronate on nitric oxide production in
      lipopolysaccharide-treated rats.
AB  - Production of nitric oxide was measured in lipopolysaccharide-treated rats (10
      mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the
      control animals, the nitric oxide level in liver of lipopolysaccharide-treated
      rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7
      to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in
      kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to
      227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and
      in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the
      antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease
      of the nitric oxide level in brain cortex and cerebellum 1 hr after drug
      administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a
      twofold decrease of the nitric oxide concentration in all studied tissues 30 min.
      after the administration. Nitric oxide reached the initial level 2 hr later.
      Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric
      oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be
      prospective drugs for the treatment of circulatory complications of sepsis.

PMID- 14725615
TI  - Valproic acid is known to cause hypospadias in man but does not reduce anogenital
      distance or causes hypospadias in rats.
AB  - The use of valproic acid during human pregnancy increases the risk of hypospadias
      in the offspring. Rats exposed in utero to valproic acid did not develop
      hypospadias and even had a slightly increased anogenital distance in males 3-4
      days after birth. A classical antiandrogenic drug, flutamide, caused hypospadias
      as well as a reduction of the anogenital distance in males. At the age of 3
      months, rats exposed in utero with either valproic acid or flutamide showed a
      reduced testicular weight and hypoplasia of tubules, which seemed not to be
      related to the antiandrogenic activity of flutamide as it did not correlate with
      the presence of hypospadias. The mechanism through which valproic acid causes
      hypospadias in man and affects testicular development in rat is unknown.
      Hypospadias caused by valproic acid in man is apparently not due to anti
      androgenic properties of the drug.

PMID- 14725616
TI  - Postsynaptic calcium contributes to reinforcement in a three-neuron network
      exhibiting associative plasticity.
AB  - We show that activation of a single serotonergic cell is sufficient to trigger
      long-term associative enhancement of synaptic input to the withdrawal interneuron
      in a simple network consisting of three interconnected identified cells in the
      nervous system of terrestrial snail Helix. 1,2-bis (2-aminophenoxy) Ethane
      N,N,N',N'-tetraacetic acid (BAPTA) injection in the postsynaptic neuron abolishes
      the pairing-specific enhancement of synaptic input. Activation of a single
      modulatory cell that we used to reinforce the synaptic input induced an increase
      of the intracellular [Ca2+] in the ipsilateral withdrawal interneuron without any
      changes of its membrane potential or input resistance. Similar changes in
      intracellular [Ca2+] were observed in the same withdrawal interneuron under bath
      application of 10(-5) m serotonin. Responses to repeated glutamate applications
      to the soma of synaptically isolated withdrawal interneurons increased after 10
      min of serotonin or thapsigargin bath application, but were absent in conditions
      of preliminary BAPTA intracellular injection, significantly decreased under
      heparin injection. Thus, activity of a single modulatory cell may mediate
      reinforcement via an increase of [Ca2+] in the postsynaptic cell in a simple
      network consisting of neurons with defined behavioural roles.

PMID- 14725617
TI  - Efficacy of doublecortin as a marker to analyse the absolute number and dendritic
      growth of newly generated neurons in the adult dentate gyrus.
AB  - Doublecortin (DCX), a microtubule-associated phosphoprotein, has been recently
      utilized as a marker of newly born neurons in the adult dentate gyrus (DG).
      Nonetheless, it is unknown whether DCX exclusively labels newly formed neurons,
      as certain granule cells with the phenotype of differentiated neurons express
      DCX. We addressed the authenticity of DCX as a marker of new neurons in the adult
      DG by quantifying cells that are positive for 5'-bromodeoxyuridine (BrdU), DCX
      and both BrdU and DCX in hippocampal tissues of adult rats treated with daily
      injections of BrdU for 12 consecutive days. We provide new evidence that neurons
      visualized with DCX immunostaining in the adult rat DG are new neurons that are
      predominantly born during the 12 days before euthanasia. This is confirmed by the
      robust expression of BrdU in 90% of DCX-positive neurons in the DG of animals
      injected with BrdU for 12 days. Furthermore, DCX expression is specific to newly
      generated healthy neurons, as virtually all DCX-positive cells express early
      neuronal antigens but lack antigens specific to glia, undifferentiated cells or
      apoptotic cells. As DCX expression is also robust in the dendrites, DCX
      immunocytochemistry of thicker sections facilitates quantification of the
      dendritic growth in newly born neurons. Thus, both absolute number and dendritic
      growth of new neurons that are generated in the adult DG over a 12-day period can
      be quantified reliably with DCX immunostaining. This could be particularly useful
      for analysing changes in dentate neurogenesis in human hippocampal tissues as a
      function of ageing or neurodegenerative diseases.

PMID- 14725618
TI  - Rearrangement of the retino-collicular projection after partial optic nerve crush
      in the adult rat.
AB  - The establishment of retino-collicular topography is a well-investigated model of
      axon pathfinding and it was believed that this topography is irreversibly fixed
      throughout life. We now report that, after partial crush of the adult rat optic
      nerve, the anterograde transport of intravitreally-injected tracers via axons of
      surviving retinal ganglion cells (RGC) in all retinal quadrants is confined to
      the rostro-medial part of the superior colliculus (SC). This indicates that the
      retino-collicular topography is rearranged after partial crush of the adult rat
      optic nerve. The reorganization starts in the injured optic nerve where surviving
      axonal fibres are demyelinized and bundled in the periphery of the optic nerve
      distal to the crush site. This is followed by a displacement of surviving axons
      to the medial part of the optic tract (OT) within 2 weeks. The infiltration of
      macrophages with the subsequent production of tumour necrosis factor-alpha at the
      lesion site is a prerequisite for the altered retino-collicular projection as
      blockade of tumour necrosis factor-alpha signalling with the neutralizing
      antibody Infliximab abolishes reorganization in the SC and lateralization of RGC
      axons in the optic nerve and OT. This suggests that optic nerve inflammation is
      necessary for a progressive bundling of surviving RGC axons, probably via
      clearance of cellular debris which, in turn, may lead to a redistribution of RGC
      axons to the medial OT and rostro-medial SC.

PMID- 14725619
TI  - Enhanced generation of intracellular Abeta42 amyloid peptide by mutation of
      presenilins PS1 and PS2.
AB  - The accumulation of amyloid beta-peptide (Abeta) in the brain is a critical
      pathological process in Alzheimer's disease (AD). Recent studies have implicated
      intracellular Abeta in neurodegeneration in AD. To investigate the generation of
      intracellular Abeta, we established human neuroblastoma SH-SY5Y cells stably
      expressing wild-type amyloid precursor protein (APP), Swedish mutant APP, APP
      plus presenilin 1 (PS1) and presenilin 2 (PS2; wild-type or familial AD
      associated mutant), and quantified intracellular Abeta40 and Abeta42 in formic
      acid extracts by sensitive Western blotting. Levels of both intracellular Abeta40
      and Abeta42 were 2-3-fold higher in cells expressing Swedish APP, compared with
      those expressing wild-type APP. Intracellular Abeta42/Abeta40 ratios were
      approximately 0.5 in these cells. These ratios were increased markedly in cells
      expressing mutant PS1 or PS2 compared with those expressing their wild-type
      counterparts, consistent with the observed changes in secreted Abeta42/Abeta40
      ratios. High total levels of intracellular Abeta were observed in cells
      expressing mutant PS2 because of a marked elevation of Abeta42.
      Immunofluorescence staining additionally revealed more intense Abeta42
      immunoreactivity in mutant PS2-expressing cells than in wild-type cells, which
      was partially colocalized with immunoreactivity for the trans-Golgi network and
      endosomes. The data collectively indicate that PS mutations promote the
      accumulation of intracellular Abeta42, which appears to be localized in multiple
      subcellular compartments.

PMID- 14725620
TI  - CNTF promotes survival of retinal ganglion cells after induction of ocular
      hypertension in rats: the possible involvement of STAT3 pathway.
AB  - We examined the neuroprotective effect of ciliary neurotrophic factor (CNTF) on
      retinal ganglion cells (RGCs) in a rat glaucoma model with increased intraocular
      pressure (IOP) and studied the CNTF-mediated activation of Janus kinase/signal
      transducer and activator of transcription (JAK-STAT) pathway. Elevated IOP was
      induced by laser photocoagulation of the episcleral and limbal veins. The
      survival of RGCs was studied using Fluoro-Gold labelled in ocular hypertensive
      eyes with or without CNTF intravitreal injection. Immunochemical staining and
      immunoblot analysis for CNTF and phosphorylated STAT3 (pSTAT3) were performed.
      There was a significant and progressive loss of RGCs in the retinas following the
      induction of elevated IOP. A single intravitreal injection of 2 microg in 2
      microL CNTF significantly protected RGCs up to 4 weeks. pSTAT3 was only
      transiently expressed in ocular hypertensive eyes. However, in eyes treated with
      CNTF, pSTAT3 was observed up to 2 weeks after the induction of elevated IOP. In
      ocular hypertensive eyes, CNTF-positive cells were found in the inner nuclear
      layer (INL), and there was a transient increase in the pSTAT3 cells in the
      ganglion cell layer and INL. Immunoblots showed that STAT3 was transiently
      phosphorylated after IOP increase, but with an injection of CNTF, pSTAT3 protein
      was observed up to 2 weeks after hypertensive glaucoma induction. Laser-induced
      chronic ocular hypertension in rats resulted in the death of RGCs and a transient
      activation of STAT3 in the retina. Intravitreal injection of CNTF showed a
      significant protection of RGCs, and the JAK-STAT signalling could be one of the
      important pathways that underlie the mechanism of CNTF neuroprotection in this
      rat glaucoma model.

PMID- 14725621
TI  - The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin
      induced toxicity by phosphorylating serine 421 of huntingtin.
AB  - Huntington's disease (HD) is caused by abnormal polyglutamine (polyQ) expansion
      in the protein huntingtin. We have previously demonstrated the importance of the
      insulin-like growth factor I (IGF-1)/Akt pathway in HD. Indeed, upon IGF-1
      activation, Akt phosphorylates polyQ-huntingtin at serine 421 and abrogates its
      toxicity. In addition, we have demonstrated that Akt is altered in the brain of
      HD patients. Here, we investigate the role of the serum- and glucocorticoid
      induced kinase (SGK) in HD. We show that SGK phosphorylates huntingtin at serine
      421 and that phosphorylation can protect striatal neurons against polyQ
      huntingtin-induced toxicity. We find that SGK levels are increased in the brain
      of HD patients. Using a cellular model of HD, we demonstrate that the SGK
      dysregulation induced by polyQ-huntingtin occurs via the p38/MAPK pathway.
      Collectively, our results strongly suggest the involvement of SGK in HD and
      further imply that IGF-1 downstream signalling is a key transduction pathway that
      regulates the toxicity of huntingtin.

PMID- 14725622
TI  - Toxicity of glutathione depletion in mesencephalic cultures: a role for
      arachidonic acid and its lipoxygenase metabolites.
AB  - The contribution of arachidonic acid (AA) release and metabolism to the toxicity
      that results from glutathione (GSH) depletion was studied in rat mesencephalic
      cultures treated with the GSH synthesis inhibitor l-buthionine sulfoximine. Our
      data show that GSH depletion is accompanied by increased release of AA, which is
      phosholipase A2 (PLA2) dependent. Exogenous AA is toxic to GSH-depleted cells.
      This toxicity is prevented by inhibition of lipoxygenase activity, suggesting
      participation of toxic byproducts of AA metabolism. Hydroxyperoxyeicosatetraenoic
      acid (HPETE), one of the primary products of AA metabolism by lipoxygenase is
      also toxic to GSH-depleted cells, whereas hydroeicosatetraenoic acid (HETE) is
      not. Cell death caused by GSH depletion is prevented by: (i) replenishment of GSH
      levels with GSH-ethyl ester; (ii) inhibition of PLA2 activity; (iii) inhibition
      of lipoxygenase activity; and (iv), treatment with ascorbic acid. These data
      suggest that the following events likely contribute to cell death when GSH levels
      become depleted. Loss of GSH results in increased release of AA, which is PLA2
      dependent. Metabolism of arachidonic acid via the lipoxygenase pathway results in
      generation of oxygen free radicals possibly produced during conversion of HPETE
      to HETE, which contribute to cellular damage and death. Our study suggests that
      limiting AA release and metabolism may provide benefit in conditions with an
      existing depletion of GSH, such as Parkinson's disease.

PMID- 14725623
TI  - Pyruvate limits zinc-induced rat oligodendrocyte progenitor cell death.
AB  - A growing body of evidence suggests that excessive Zn2+ release plays a key role
      in inducing neuronal death during central nervous system injury. However, the
      possible cytotoxicity of extracellular Zn2+ to oligodendrocyte lineage cells
      remains unknown. Employing cultures of rat oligodendrocyte progenitor cells
      (OPC), we report here that OPC are vulnerable to increased extracellular Zn2+
      levels and that pyruvate limits Zn2+-induced OPC death. Zn2+-induced
      concentration-dependent (pEC50 = -4.1 +/- 0.1) OPC death, which was insensitive
      to both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (Evans
      Blue) and l-type Ca2+ channel (nicardipine) inhibition. Neither kainate nor
      nicardipine influenced OPC 65Zn2+ accumulation, in contrast with the Zn2+
      ionophore, pyrithione. Cytotoxic extracellular Zn2+ concentrations failed to
      increase OPC reactive oxygen species production and the antioxidant reagents,
      trolox, N,N'-diphenyl-1,4-phenylenediamine and N-tert-butyl-alpha-phenylnitrone
      did not afford significant protection from Zn2+ insults. The apoptotic inducer
      staurosporine induced the appearance of known apoptotic markers [pyknotic nuclei
      and caspase-3 specific (120 kDa) alpha-fodrin cleavage fragment], events not
      reproduced with Zn2+ insults. Zn2+ insults were also insensitive to the pan
      caspase inhibitor Z-VAD-fmk. However, pyruvate afforded significant OPC
      protection from lethal Zn2+ insults. We conclude that cultured OPC are vulnerable
      to Zn2+ insults, via a nonoxidative stress and noncaspase-3-based mechanism,
      involving Zn2+ inhibition of OPC glycolysis.

PMID- 14725624
TI  - Reticular stimulation evokes suppression of CA1 synaptic responses and generation
      of theta through separate mechanisms.
AB  - The induction of hippocampal theta by reticular stimulation involves a relay to
      the hippocampus via the posterior hypothalamic-supramammillary region and then
      the medial septum. Interestingly, sensory- or behaviour-induced theta is
      accompanied by suppression of hippocampal field CA1 synaptic responses. In the
      present study, performed on anaesthetized rats, we observed that reticular
      stimulation also induced a suppression of the CA1 pyramidal cell population spike
      and the corresponding dendritic field excitatory postsynaptic potential evoked by
      field CA3 stimulation. This suppression was observed at stimulation intensity
      below the threshold for generation of CA1 theta and was maximal at stimulation
      intensities at the threshold for theta. The frequency and amplitude of theta
      waves, by contrast, increased further with increasing reticular stimulation
      voltage. Neural inactivation by microinjection of the local anaesthetic procaine
      (20% w/v, 0.1-0.2 microL) or the inhibitory ligand gamma aminobutyric acid (0.8
      m, 0.5 micro L) in the posterior hypothalamic regions, especially the ipsilateral
      medial supramammillary region, or the medial septum attenuated both the
      suppression of CA1 pyramidal cell synaptic excitability and theta generation.
      However, the effects of microinjection on suppression and theta were not always
      in parallel. Furthermore, the effect of microinjection of gamma aminobutyric acid
      on reticularly elicited suppression was observed from relatively fewer sites in
      the posterior hypothalamus as compared with that on theta activation. These
      results suggest that reticular stimulation evokes an inhibition of CA1 pyramidal
      cell excitability that (i) is mediated, at least in part, via medial
      supramammillary and septal regions, but (ii) involves a separate neural pathway
      from theta generation.

PMID- 14725625
TI  - Median raphe mediates estrogenic effects to the hippocampus in female rats.
AB  - Subcortical regions such as the medial septum-diagonal band of Broca and
      supramammillary area have been shown to mediate indirect oestrogenic effects on
      hippocampal morphology and function. Here, the role of the median raphe (MR), a
      serotonergic subcortical structure, is studied. To this end, 17beta-estradiol
      filled 30-gauge cannulae were implanted into the MR of female ovariectomized
      rats; cholesterol-filled cannulae served as controls. After seven days, using
      unbiased electron microscopic stereological calculations and semiquantitative
      analysis, the spine synapse density and surface density of glial fibrillary
      acidic protein-positive astrocyte processes, respectively, were determined in the
      stratum radiatum of the CA1 region of the hippocampus. Changes in the
      serotonergic innervation of the hippocampal CA1 region were determined by
      immunohistochemistry and subsequent morphometric analysis. In the stratum
      radiatum of the CA1 region, local estradiol application into the MR resulted in a
      47% increase in spine synapse density. Simultaneously, the density of glial
      fibrillary acidic protein-positive fibers decreased by 16%. The density of
      serotonin (5-HT) innervation of the strata lacunosum moleculare and radiatum of
      the CA1 region of the hippocampus was reduced in response to estradiol, as shown
      by a decrease in the length of fibers (27.6 and 48.3% decrease, respectively) and
      the number of large varicosities (32.5 and 38.8% decrease, respectively). These
      observations suggest a major role of the MR in mediating oestrogenic effects on
      the hippocampus and an involvement of the serotonergic system.

PMID- 14725626
TI  - Glutamatergic clock output stimulates melatonin synthesis at night.
AB  - The rhythm of melatonin synthesis in the rat pineal gland is under the control of
      the biological clock, which is located in the suprachiasmatic nucleus of the
      hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence
      of the SCN on melatonin synthesis, by using gamma-aminobutyric acid input to the
      paraventricular nucleus of the hypothalamus (PVN). Nevertheless, a recent lesion
      study suggested the presence of a stimulatory clock output in the control of the
      melatonin rhythm as well. In order to further investigate this output in acute in
      vivo conditions, we first measured the release of melatonin in the pineal gland
      before, during and after a temporary shutdown of either SCN or PVN neuronal
      activity, using multiple microdialysis. For both targets, SCN and PVN, the
      application of tetrodotoxin by reverse dialysis in the middle of the night
      decreased melatonin levels. Due to recent evidence of the existence of
      glutamatergic clock output, we then studied the effect on melatonin release of
      glutamate antagonist application within the PVN in the middle of the night.
      Blockade of the glutamatergic input to the PVN significantly decreased melatonin
      release. These results demonstrate that (i) neuronal activity of both PVN and SCN
      is necessary to stimulate melatonin synthesis during the dark period and (ii)
      glutamatergic signalling within the PVN plays an important role in melatonin
      synthesis.

PMID- 14725627
TI  - Kv1 currents mediate a gradient of principal neuron excitability across the
      tonotopic axis in the rat lateral superior olive.
AB  - Principal neurons of the lateral superior olive (LSO) detect interaural intensity
      differences by integration of excitatory projections from ipsilateral bushy cells
      and inhibitory inputs from the medial nucleus of the trapezoid body. The
      intrinsic membrane currents active around firing threshold will form an important
      component of this binaural computation. Whole cell patch recording in an in vitro
      brain slice preparation was employed to study conductances regulating action
      potential (AP) firing in principal neurons. Current-clamp recordings from
      different neurons showed two types of firing pattern on depolarization, one group
      fired only a single initial AP and had low input resistance while the second
      group fired multiple APs and had a high input resistance. Under voltage-clamp,
      single-spiking neurons showed significantly higher levels of a dendrotoxin
      sensitive, low threshold potassium current (ILT). Block of ILT by dendrotoxin-I
      allowed single-spiking cells to fire multiple APs and indicated that this current
      was mediated by Kv1 channels. Both neuronal types were morphologically similar
      and possessed similar amounts of the hyperpolarization-activated nonspecific
      cation conductance (Ih). However, single-spiking cells predominated in the
      lateral limb of the LSO (receiving low frequency sound inputs) while multiple
      firing cells dominated the medial limb. This functional gradient was mirrored by
      a medio-lateral distribution of Kv1.1 immunolabelling. We conclude that Kv1
      channels underlie the gradient of LSO principal neuron firing properties. The
      properties of single-spiking neurons would render them particularly suited to
      preserving timing information.

PMID- 14725628
TI  - The antiepileptic drug levetiracetam selectively modifies kindling-induced
      alterations in gene expression in the temporal lobe of rats.
AB  - Gene expression profiling by microarrays is a powerful tool for identification of
      genes that may encode key proteins involved in molecular mechanisms underlying
      epileptogenesis. Using the Affymetrix oligonucleotide microarray, we have
      surveyed the expression levels of more than 26,000 genes and expressed sequence
      tags (ESTs) in the amygdala-kindling model of temporal lobe epilepsy.
      Furthermore, the effect of the antiepileptic drug levetiracetam (LEV) on kindling
      induced alterations of gene expression was studied. Treatment of rats with LEV
      during kindling acquisition significantly suppressed kindling development. For
      gene expression profiling, six groups of rats were included in the present study:
      (i) and (ii) sham-operated rats treated with saline or LEV; (iii) and (iv)
      electrode-implanted but non-kindled rats treated with saline or LEV; (v) and (vi)
      kindled rats treated with saline or LEV. Treatment was terminated after 11 or 12
      daily amygdala stimulations, when all vehicle-treated rats had reached kindling
      criterion, i.e. a stage 5 seizure. Twenty-four hours later, the ipsilateral
      temporal lobe was dissected for mRNA preparation. Six temporal lobe preparations
      from each group were analysed for differential gene expression. In control (non
      kindled) rats, LEV treatment was devoid of any significant effect on gene
      expression. In saline-treated kindled rats, a large number of genes were observed
      to display mRNA expression alterations compared with non-kindled rats. LEV
      treatment induced marked effects on gene expression from kindled rats. Previously
      described epilepsy-related genes, such as neuropeptide Y (NPY), thyrotropin
      releasing hormone (TRH) and glial fibrillary acidic protein (GFAP) were confirmed
      to be up-regulated by kindling and partially normalized by LEV treatment. Real
      time quantitative polymerase chain reaction confirmed NPY, TRH and GFAP
      expression data from chip experiments. Furthermore, a number of novel genes were
      identified from the gene chip experiments. A subgroup of these genes demonstrated
      correlation between expression changes and kindled phenotype measurements. In
      summary, this study identified many genes with potentially important roles in
      epileptogenesis and highlighted several important issues in using the gene chip
      technology for the study of animal models of CNS disorders.

PMID- 14725629
TI  - Turning behaviour induced by stimulation of the 5-HT receptors in the subthalamic
      nucleus.
AB  - The basal ganglia, which receive a rich serotonergic innervation, have been
      implicated in hyperkinetic and hypokinetic disorders. Moreover, a decrease in
      subthalamic nucleus (STN) activity has been associated with motor hyperactivity.
      To address the role of subthalamic serotonergic innervation in its motor
      function, turning behaviour was studied in rats with stimulation of the
      subthalamic serotonin (5-HT) receptors by intracerebral microinjections. The
      intrasubthalamic administration of 5-HT induced dose-dependent contralateral
      turning behaviour, with a maximal effect at a dose of 2.5 microg in 0.2 microL.
      Similar results were observed with microinjections of other 5-HT receptor
      agonists: quipazine (a 5-HT2B/C/3 agonist), MK-212 (a 5-HT2B/C agonist) and m
      chlorophenylbiguanidine (a 5-HT3 agonist), while microinjections of 5-HT into the
      zona incerta or in the previously lesioned STN were ineffective. The effect of 5
      HT was blocked by coadministration of the antagonist mianserin. Stimulation of
      subthalamic 5-HT receptors in animals bearing a lesion of the nigrostriatal
      pathway did not modify the motor response, which indicates that the dopamine
      innervation of the nucleus is not involved in this effect. Kainic acid lesion of
      the substantia nigra pars reticulata (SNr) suppressed the contralateral rotations
      elicited by stimulation of 5-HT2B/C/3 subthalamic receptors. This suggests a role
      of the subthalamic-nigral pathway in the turning activity. Furthermore, the
      partial blockade of glutamatergic receptors in the SNr by the antagonist DNQX
      increased the contralateral circling elicited by stimulation of 5-HT receptors in
      the STN. We concluded that the activation of the 5-HT2B/C and 5-HT3 subthalamic
      receptors elicited contralateral turning behaviour, probably via the subthalamic
      nigral pathway.

PMID- 14725630
TI  - Activity-dependent persisting modification of polysynaptic neural circuits
      involving layer V pyramidal neurons in rat auditory cortex in vitro.
AB  - Synaptic plasticity in polysynaptic neural circuits permits modulation of the
      dynamic properties of these circuits. We investigated the properties of
      polysynaptic potentiation in pyramidal neurons in layer V of rat auditory cortex
      (AC) slices using the perforated patch clamp technique. The GABAA receptor
      inhibitor bicuculline was used to facilitate polysynaptic activity. The amplitude
      and duration of the polysynaptic activity were both gradually potentiated with
      repetitive stimulation (RS) at 12 s intervals. Potentiation was saturated within
      10 min of the onset of RS. After the cessation of RS, the polysynaptic responses
      returned to control levels within 30 min. RS-induced potentiation was confirmed
      by fluorescence imaging of slices loaded with the Ca2+ indicator rhod-2. Such
      potentiation was not induced by stimulation at 60 s intervals. The magnitude of
      the RS-induced potentiation in layer V pyramidal neurons in the AC was greater
      than that in either layer II/III pyramidal neurons in the AC or layer V pyramidal
      neurons in the visual cortex. The NMDA receptor antagonist APV (100 microm),
      inhibited RS-induced potentiation. When stimulated at 1 Hz, the potentiated
      response appeared rapidly. In the absence of bicuculline, RS consisting of five
      pulses at 30 ms intervals, repeated at 12 s intervals for 10 min, elicited
      potentiation of firing activity, suggesting that the potentiation is independent
      of bicuculline. The present study demonstrates the dynamic properties of
      polysynaptic circuits involving layer V pyramidal neurons in the AC are strongly
      affected by activity-dependent synaptic potentiation.

PMID- 14725631
TI  - Cyclin S: a new member of the cyclin family plays a role in long-term memory.
AB  - Memory is thought to be subserved by structural and functional alteration in
      synaptic connectivity. But although neuronal plasticity requires gene expression,
      the identity of the proteins involved is largely unknown. Using the chick 1-day
      old passive avoidance learning paradigm and differential display RNA
      fingerprinting, we identified 13 candidate genes which are upregulated in the
      intermediate medial hyperstriatum ventrale (IMHV), an area that has been
      correlated with the initial processing of memory formation. One of the induced
      genes is a new member of the cyclin family, with high homology to cyclin L (ania
      6a). Analysis of the expression pattern of this gene after training revealed two
      time waves of induction: the first correlated with learning and initial memory
      process in the IMHV; the second correlated with memory consolidation, first in
      the IMHV, and then in the lobus paraolefactoris. There is a correlation between
      methylanthranilate (MeA) concentrations (the malaise substrate in the passive
      avoidance training procedure), the duration of memory and the expression level of
      cyclin S. While training chicks on low concentrations of MeA causes short-term
      memory and low expression level of cyclin S, high concentration of MeA induces
      long-term memory and high expression level of cyclin S in the IMHV. The role of
      cyclins in the regulation of neuronal-plasticity-related gene expression was
      overlooked, and it might serve as a key step in long-term memory formation.

PMID- 14725632
TI  - Activation of a subpopulation of orexin/hypocretin-containing hypothalamic
      neurons by GABAA receptor-mediated inhibition of the nucleus accumbens shell, but
      not by exposure to a novel environment.
AB  - Gamma-amino butyric acid (GABA)A receptor stimulation in the nucleus accumbens
      shell produces intense hyperphagia in rats and increases Fos expression in the
      lateral hypothalamus. To explore the involvement of hypothalamic
      orexin/hypocretin- or melanin concentrating hormone-immunoreactive neurons in
      this effect, the GABAA agonist, muscimol (0, 50 ng), was infused directly into
      the nucleus accumbens shell of rats; 90 min later, their brains were collected
      and subsequently processed for immunohistochemistry. A group exposed to a novel
      environment was included to evaluate the specificity of Fos expression changes
      with regard to general arousal. Alternating sections through the hypothalamus
      were double-stained for orexin/hypocretin-Fos or melanin concentrating hormone
      Fos combinations. Intra-accumbens shell muscimol treatment significantly
      increased the percentage of orexin/hypocretin-containing neurons expressing Fos
      in the lateral, but not medial, portion of the perifornical/lateral hypothalamic
      area. Regardless of treatment condition, greater percentages of orexin/hypocretin
      containing neurons in the medial portion of the hypothalamus expressed Fos
      relative to cells located more laterally. None of the manipulations increased Fos
      expression in melanin concentrating hormone-immunoreactive neurons. Muscimol
      treatment also markedly increased Fos expression in the arcuate nucleus, which
      connects reciprocally to the lateral/perifornical hypothalamic area. Thus,
      orexin/hypocretin-containing neurons in lateral sectors of the hypothalamus,
      along with cells in the arcuate nucleus, display phasic increases in Fos
      expression after an orexigenic pharmacological manipulation of the nucleus
      accumbens shell, but to a lesser degree after the heightened arousal associated
      with exposure to a novel environment.

PMID- 14725633
TI  - Neonatal 5HT activity antagonizes the masculinizing effect of testosterone on the
      luteinizing hormone release response to gonadal steroids and on brain structures
      in rats.
AB  - Hypothalamic 5HT concentrations are transiently lower in male compared to female
      Wistar rats in the second week post partum (pp) and our previous findings have
      shown that pharmacologically potentiating 5HT activity over this period feminizes
      certain aspects of sexually differentiated behaviours in adult males and
      androgenized females. In order to investigate whether neonatal testosterone and
      5HT interact to influence physiological and morphological brain sexual
      differences, females, androgenized females and males were treated with the 5HT2
      agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days
      8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp)
      (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen
      induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI
      overcame the neonatal androgen effect in suppressing the positive feedback of
      ovarian steroids in a few males and androgenized females. (-) DOI had a
      feminizing effect on the volume of the anteroventral periventricular nucleus
      (normally smaller in males), by significantly increasing its volume in male and
      androgenized females. It also had a significant antagonistic effect on the
      testosterone-induced increase in the volume of the sexually dimorphic nucleus of
      the preoptic area in males and androgenized females. These findings support the
      view that raised 5HT activity in the second week of life antagonizes the
      masculinizing effect of neonatal testosterone.

PMID- 14725634
TI  - Modulation of feeding behaviour by blocking purinergic receptors in the rat
      nucleus accumbens: a combined microdialysis, electroencephalographic and
      behavioural study.
AB  - The nonspecific P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS), the nonspecific P1 receptor antagonist 8-(p
      sulphophenyl)-theophylline (8-SPT) and the combination of both were applied by
      retrograde microdialysis into the nucleus accumbens (NAc) before and during
      feeding of 18-h food-deprived rats. In addition to the registration of
      behavioural parameters, such as the amount and duration of food intake, the
      feeding-induced changes in dopamine (DA) concentration and the concomitant
      changes of neuronal activity in the NAc and the ventral tegmental area (VTA) were
      simultaneously determined. The perfusion with PPADS (20 microm) diminished the
      amount of food intake and the duration of feeding. Furthermore, the P2 receptor
      antagonist blocked the feeding-induced DA release and prevented the feeding
      elicited changes of the electroencephalography (EEG) power distribution which was
      characterised by an increase in the power of the 8.0-13.0-Hz frequency band in
      the NAc and the VTA. The effects of PPADS could be completely prevented by the
      concomitantly perfused adenosine receptor antagonist 8-SPT (100 microm). When
      given alone, 8-SPT increased the amount of food ingested, the duration of feeding
      and the EEG power of the higher frequency range, particularly between 19.0 and
      30.0 Hz, in both the NAc and the VTA. The feeding-elicited DA release was
      supplemented to the enhanced DA level caused by the perfusion with 8-SPT in an
      additive manner. The P2 and P1 receptor antagonists interact antagonistically in
      the modulation of feeding behaviour and the feeding-induced changes of EEG
      activity suggesting that both endogenous extracellular ATP and adenosine are
      involved in the regulation of the feeding-associated mesolimbic neuronal activity
      in a functionally antagonistic manner.

PMID- 14725635
TI  - Suppressing calcium/calmodulin-dependent protein kinase II activity in the
      ventral tegmental area enhances the acute behavioural response to cocaine but
      attenuates the initiation of cocaine-induced behavioural sensitization in rats.
AB  - In the present experiments we administered an alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) receptor antagonist (CNQX), N-methyl-D-aspartate
      (NMDA) receptor antagonist (AP-5), or l-type calcium channel blocker (diltiazem)
      directly into the ventral tegmental area (VTA) before each of four daily systemic
      cocaine injections in order to assess their influence on the initiation phase of
      behavioural sensitization. Results indicated that pretreatment with CNQX or AP-5
      impaired the initiation of cocaine-induced behavioural sensitization. Intra-VTA
      administration of diltiazem significantly increased the behavioural activation
      induced by an acute cocaine injection, but impaired the development of cocaine
      induced behavioural sensitization. Because AMPA and NMDA receptors, as well as l
      type calcium channels are calcium permeable, we also investigated the role of the
      calcium-activated second messenger calcium/calmodulin-dependent protein kinase II
      (CaM-KII). Similar to the results obtained with diltiazem, administration of the
      CaM-KII inhibitor KN-93 into the VTA enhanced the acute behavioural response to
      cocaine but prevented the augmentation of cocaine-induced behavioural
      hyperactivity following repeated injections. Consistent with this finding, the
      behavioural hyperactivity produced by cocaine was markedly enhanced among
      homozygous alpha-CaM-KII knockout mice but the initiation of behavioural
      sensitization to cocaine was attenuated relative to wild-type mice. Separate
      experiments performed in rats demonstrated an increase in total protein levels of
      CaM-KII in the VTA 24 h after the last of seven daily injections of cocaine.
      Taken together, these results indicate that blocking l-type calcium channels or
      impairing CaM-KII activity in the VTA augments the acute behavioural
      hyperactivity induced by cocaine. The present findings also suggest that
      increased calcium influx through AMPA receptors, NMDA receptors and l-type
      calcium channels on dopaminergic neurons in the VTA contributes significantly to
      the initiation of behavioural sensitization by amplifying calcium signalling
      through CaM-KII.

PMID- 14725636
TI  - Selective deficits in appetitive conditioning as a consequence of ethanol
      withdrawal.
AB  - The acquisition of a conditioned response to a cue associated with a fearful
      event has been shown to be impaired in animals that had been repeatedly withdrawn
      from ethanol, but not in animals with the same chronic ethanol treatment but only
      a single withdrawal episode [D. N. Stephens et al. (2001) Eur. J. Neurosci., 14,
      2023-2031]. Lesion studies have shown that the amygdala plays a vital role in
      this type of conditioning process. Here we investigate aspects of conditioning
      for appetitive reinforcers in operant tasks, also shown to rely on amygdala
      processing, in rats following repeated withdrawal from ethanol. Rats were
      chronically treated with either an ethanol-containing liquid diet for 24 days
      continuously (single withdrawal) or interspersed with 2 x 3-day withdrawal
      periods (repeated withdrawal), or with a control diet (control). Two weeks after
      the final withdrawal, operant training began. In tasks that are impaired by
      lesions of the basolateral amygdala, conditioned reinforcement and reinforcer
      devaluation, there was no effect of chronic ethanol treatment or withdrawal on
      acquisition or performance. However, in a task that is dependent upon functioning
      of the central nucleus of the amygdala, Pavlovian-to-instrumental transfer, the
      single and repeated withdrawal groups were significantly impaired. Therefore,
      chronic ethanol treatment and withdrawal resulted in deficits in behavioural
      tasks that are sensitive to central but not to basolateral amygdala lesions, and
      may reflect different sensitivities of these areas to ethanol.

PMID- 14725637
TI  - Disruption of self-organized actions in monkeys with progressive MPTP-induced
      parkinsonism. I. Effects of task complexity.
AB  - Parkinson's disease (PD) is characterized by motor symptoms, usually accompanied
      by cognitive deficits. The question addressed in this study is whether complexity
      of routine actions can exacerbate parkinsonian disorders that are often
      considered to be motor symptoms. To examine this question, we trained four vervet
      monkeys (Cercopithecus aethiops) to perform three multiple-choice retrieval
      tasks. In order of ascending complexity, rewards were freely available (task 1),
      covered with transparent sliding plaques (task 2), and covered with opaque
      sliding plaques cued by symbols (task 3). Thus, from task 1 to task 2 we added a
      motor difficulty--the recall of context-adapted movement; and from task 2 to task
      3 we added a cognitive difficulty: the recall of symbol-reward associations. The
      more complex the task, the longer it took to learn, but after extensive training
      the performance was stable in all tasks, with similar retrieval durations. The
      monkeys then received systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) injections (0.3-0.4 mg/kg) every 4-7 days, until the first motor symptoms
      appeared. In the course of MPTP intoxication, the behavioural performance
      declined while the motor symptoms were absent or mild--the retrieval duration
      increased, and non-initiated choices and hesitations between choices became
      frequent. Interestingly, this decline was in proportion to task complexity, and
      was particularly pronounced with the cognitive difficulty. Furthermore, freezing
      appeared only with the cognitive difficulty. We therefore suggest that everyday
      cognitive difficulties may exacerbate hypokinesia (lack of initiation, abnormal
      slowness) and executive disorders (hesitations, freezing) in the early stages of
      human PD.

PMID- 14725638
TI  - Disruption of self-organized actions in monkeys with progressive MPTP-induced
      parkinsonism: II. Effects of reward preference.
AB  - The motor and cognitive symptoms of Parkinson's disease (PD) are well documented,
      but little is known about the functionality of motivational processes mediated by
      the limbic circuits of basal ganglia. The aim of this study was to test the
      ability of motivational processes to direct and to urge behaviour, in four vervet
      monkeys (Cercopithecus aethiops) progressively intoxicated with systemic 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg every 4-7
      days). In the food preference task, the monkeys had to retrieve two types of
      directly visible food, simultaneously available in the wells of a reward board.
      At all stages of MPTP-induced parkinsonism, the monkeys continued to take their
      favourite food first. In the symbol discrimination task, the wells were covered
      with sliding plaques cued by symbols indicating the absence or presence of a
      reward, and the different types of food were blocked in separate sessions.
      Monkeys with mild or moderate parkinsonism made fewer attempts and took longer to
      retrieve non-preferred compared with preferred rewards. These results indicate
      that motivational processes are still able to direct (food preference task) and
      to urge (symbol discrimination task) behaviour in MPTP-lesioned monkeys. Such a
      functional preservation may be related to the relatively spared dopaminergic
      innervation of the limbic circuits that we found in our monkeys, in agreement
      with the literature on humans. Furthermore, the frequency of executive disorders
      (such as hesitations and freezing) appeared to be much lower with the preferred
      rewards. Thus, the preserved motivational processes may help to overcome
      executive dysfunction in the early stages of human PD.

PMID- 14725639
TI  - Properties of delay-period neuronal activity in the primate prefrontal cortex
      during memory- and sensory-guided saccade tasks.
AB  - The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term
      (or working) memory. Its cellular basis has been widely examined using the
      delayed-response paradigm in nonhuman primates. Sustained delay-period activity
      in DLPFC neurons with directional difference (i.e. directional delay-period
      activity) has been thought to represent visuospatial short-term (or working)
      memory. However, little is known about the activity of these neurons during a
      delay period when the sensory input remains. To address this issue, we examined
      neuronal activity in the DLPFC while macaque monkeys performed a memory-guided
      saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task
      required a memory-guided saccade for a remembered target location. The VGS task
      had the same temporal sequence as the MGS task, but the sensory stimulus remained
      during the delay period. We found that most of the DLPFC neurons with directional
      delay-period activity showed sustained activation during the 'delay' period in
      the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%).
      Neurons showing directional delay-period activity in the MGS task only ('M
      neurons') were only 5% of the DLPFC neurons with directional delay-period
      activity. These findings indicate that most DLPFC neurons that are active during
      the delay period are also active when the sensory stimulus remains, suggesting
      that DLPFC neurons driven by mnemonic information are also driven by sensory
      input. Such sustained representation of information should have potential utility
      in flexible cognitive controls of behaviour.

PMID- 14725640
TI  - The role of the anterior cingulate cortex in pitch variation during sad affect.
AB  - We examined neural activity, in the frontal lobes, associated with speech
      production during affective states. Using functional magnetic resonance imaging
      (fMRI), the blood oxygen level-dependent (BOLD) response to the overt reading of
      emotionally neutral sentences was measured before and after a happy or sad mood
      induction. There was no explicit demand to produce affect-congruent speech and a
      cover story was used to de-emphasize the significance of the speech task in light
      of our experimental aims. Each fMRI measurement was acquired 6 s after the onset
      of sentence presentation so that speech could be recorded while the scanner noise
      was minimal; speech parameters (e.g. pitch variation) were extracted from the
      sentences and regressed against fMRI data. In the sad group we found the
      predicted changes in affect and pitch variation. Further, the fMRI data confirmed
      our hypothesis in that the 'reading effect' (i.e. the BOLD response to reading
      minus the BOLD response to baseline stimuli) in the supracallosal anterior
      cingulate cortex covaried negatively with both pitch variation and affect. Our
      results suggest that the anterior cingulate cortex modulates paralinguistic
      features of speech during affective states, thus placing this neural structure at
      the interface between action and emotions.

PMID- 14725641
TI  - Magnetoencephalography indicates finger motor somatotopy.
AB  - The existence or non-existence of fine-scale motor somatotopy of the hand is a
      fundamental problem with regard to the functioning of the human brain. In
      contrast to seldom contradicted early twentieth century descriptions of
      activation overlap, descriptions of finger motor somatotopy faced disagreement.
      Recent blood-flow-related brain mapping data achieved with functional magnetic
      resonance imaging (fMRI) argue in favour of fine-scale somatotopy. However,
      considerable discrepancies between blood oxygen-level-dependent fMRI activations
      and intracortically recorded neuronal activity have been reported and it is
      unclear whether the blood flow results truly reflect the neuronal situation. We
      have used recent advances in magnetoencephalography to detect signals deriving
      directly from neuronal tissue. Besides replication of the overlap aspect, we
      found statistically significant evidence for the existence of a somatotopic
      aspect of human hand motor representation when comparing the fifth and first
      finger motor dipoles along the superior-inferior axis. The average location of
      the fifth finger was found to be 2.31 mm superior to the first finger.

PMID- 14725642
TI  - Superior tactile performance and learning in professional pianists: evidence for
      meta-plasticity in musicians.
AB  - Musician's brains constitute an interesting model for neuroplasticity. Imaging
      studies demonstrated that sensorimotor cortical representations are altered in
      musicians, which was assumed to arise from the development of skilled
      performance. However, the perceptual consequences of the cortical changes remain
      elusive. Here we ask whether cortical reorganization induced by professional
      musical skill training is paralleled by the evolution of other, unrelated
      perceptual abilities. We therefore studied psychophysically tactile spatial
      acuity as an indirect marker of cortical changes in professional pianists and non
      musician control subjects using a simultaneous two-point discrimination paradigm.
      We show that long-lasting piano practising resulted in lower spatial
      discrimination thresholds in comparison to non-musicians. In musicians,
      individual discrimination thresholds were linearly correlated with the daily
      training duration, indicating a direct link between tactile acuity and the degree
      of piano practising. To investigate whether the superior acuity in pianists is
      subject to further improvement, we used a Hebbian stimulation protocol of tactile
      coactivation known to improve spatial tactile acuity. Three hours of coactivation
      further reduced their discrimination thresholds. The coactivation-induced gain in
      pianists was significantly larger in comparison to control subjects and
      correlated with the years of heavy daily practising (>3 h/day), but not with the
      total years including casual playing. Our results suggest that despite already
      high-level performance in pianists, Hebbian learning was more effective in
      musicians than in controls. This implies stronger capacities for plastic
      reorganization and points to enhanced learning abilities implicating a form of
      meta-plasticity in professional pianists.

PMID- 14725643
TI  - Neuronal protein kinase C gamma-dependent proliferation and hypertrophy of spinal
      cord astrocytes following repeated in vivo administration of morphine.
AB  - Repeated administration of morphine induced a time-dependent inhibition of the
      morphine-induced antinociceptive action, indicating the development of tolerance
      to morphine. We demonstrated that mice tolerant to morphine exhibited a
      significant increase in the level of protein kinase Cgamma-like immunoreactivity
      (PKCgamma-IR) in the dorsal horn of the spinal cord. The PKCgamma-IR was
      exclusively colocalized with the neuron-specific markers neuronal nuclei (NeuN)
      and microtubule associated protein 2ab (MAP2ab). Here we found a dramatic
      increase in reactive astrocytes in the dorsal horn of the spinal cord following
      repeated treatment with morphine, as characterized by the increase and
      morphological changes in glial fibrillary acidic protein (GFAP)-positive cells.
      Furthermore, transgenic mice that express enhanced green fluorescent protein
      (EGFP) under the control of the mouse GFAP promoter displayed enhanced levels of
      EGFP expression after repeated treatment with morphine. Under these conditions,
      mice lacking the PKCgamma gene failed to show any changes in astroglial
      hypertrophy or proliferation after repeated treatment with morphine. These
      findings strongly support the idea that the sustained activation of neuronal
      PKCgamma is implicated in the increased levels of reactive astrocytes in the
      dorsal horn of the spinal cord following repeated treatment with morphine. This
      neuron-glia communication may lead to the development of tolerance to morphine
      induced antinociception.

PMID- 14725644
TI  - Stimulus locking and feature selectivity prevail in complementary frequency
      ranges of V1 local field potentials.
AB  - The local field potential (LFP) is a population measure of neuronal activity
      complementary to spike trains. Whereas the response properties of the spiking
      activity in the visual cortex have been characterized extensively, the responses
      of the LFP have not been well explored. No coherent picture exists about which
      frequency ranges exhibit feature tuning or show stimulus locked activity.
      Addressing this, we recorded LFP in the primary visual cortex of alert cats and
      calculated the tuning indices for orientation, spatial and temporal frequency.
      Furthermore, we quantified the locking of the power in different LFP frequency
      bands to the velocity profile of artificial and natural stimuli. We found that
      the LFP in alert animals is well tuned with similar specificity to orientation,
      spatial frequency and temporal frequency. Tuning to these features is most
      prominent in two frequency bands (8-23 Hz and 39-109 Hz). In two complementary
      frequency bands (23-39 Hz and above 109 Hz) the dynamics of the LFP power is
      locked tightly to the temporal structure of the stimulus. This locking is
      furthermore independent of the spatial structure of the stimulus. Together these
      four frequency bands cover the whole frequency range investigated. In contrast to
      previous studies, which often reported correlates of visual processing only in a
      limited frequency range of the LFP, the present results suggest that the entire
      frequency range of the LFP can be assigned a role in visual processing.

PMID- 14725645
TI  - Selective cholinergic denervation of the cingulate cortex impairs the acquisition
      and performance of a conditional visual discrimination in rats.
AB  - Results from excitotoxic lesion studies have implicated the cingulate cortex and
      its basal forebrain afferents in the acquisition and performance of conditional
      discrimination tasks. In the present work, we sought to clarify the role of
      specifically cholinergic projections from the vertical limb nucleus of the
      diagonal band (VDB) to the cingulate cortex in conditional visual discrimination
      (CVD) learning and performance in rats. We injected the cholinergic immunotoxin
      192 IgG-saporin into the cingulate cortex to produce selective retrograde lesions
      of the cholinergic neurons projecting from the VDB to the cingulate cortex with
      the aim of sparing afferents of non-cingulate regions that can be disrupted by
      excitotoxic or immunotoxic VDB injections and non-cholinergic VDB projections
      that can also be damaged by excitotoxic lesions. Rats sustaining selective
      cholinergic denervation in this manner were significantly impaired relative to
      sham-operated animals in the acquisition and performance of a CVD rule of the
      type 'If lights are flashing FAST, press the left lever; if SLOW, press right'.
      Asymptotic performance of the lesion group was substantially lower than for
      control rats, indicating an enduring performance deficit. This impairment was
      associated with a selective disruption on trials with the FAST flashing stimulus.
      The results confirm the involvement of cholinergic innervation of the cingulate
      cortex in CVD performance; however, the nature of the deficit suggests a role for
      cholinergic modulation in task-relevant stimulus processing rather than stimulus
      response learning per se.

PMID- 14725647
TI  - Smoking and disease.
AB  - Tobacco represents the single most preventable cause of disease and death in the
      world today. The countries of Central Europe bear a disproportionate burden of
      tobacco-related morbidity and mortality. For example, some of the highest rates
      worldwide of cigarette consumption and smoking prevalence are in the Czech
      Republic, Hungary and Romania. This chapter first describes the extent of tobacco
      use in five central European countries, the Czech Republic, Hungary, Poland,
      Romania and Slovakia and then considers mortality from tobacco related disease.
      Data from two diseases, lung cancer and oral cancer, which result almost
      exclusively from tobacco use are considered. Finally, the relationship between
      tobacco use and oral disease is discussed.

PMID- 14725648
TI  - Approaches to tobacco control: the evidence base.
AB  - Tobacco production, distribution, and use are international issues with
      significant health and economic implications. This paper provides an overview of
      the effective approaches to tobacco control including decreasing demand for
      tobacco products through taxation, consumer education, research, bans on
      advertising and promotion, warning labels, and restrictions on public smoking.
      The effectiveness of reducing the supply of tobacco products through prohibition,
      restrictions on youth access, crop substitution, trade restrictions, and control
      of smuggling, will also be discussed. Decreasing smoking, particularly among
      young people, by preventing or delaying initiation, preventing regular use, and
      increasing cessation through behavioural approaches for all ages is reviewed.
      Cessation methods including pharmacological approaches, 'quitlines', Internet
      programmes, and the targeting of specific populations are discussed. Internet
      availability of tobacco products and sustainability of current efforts are
      presented as continuing challenges to tobacco control.

PMID- 14725649
TI  - The role of the dental team in tobacco cessation.
AB  - The dental team can play an effective role in the creation of tobacco-free
      communities and individuals through participation in community and political
      action and in counselling their patients to quit. Maintaining a smoke-free
      environment is important. There are well-tried and cost effective methods for
      brief interventions in dental clinical settings, and team-work, to which both
      clinical and reception/administrative staff must contribute, is fundamental. Quit
      rates of the order of 10%, sustained over a year or more, can be achieved and
      this may be increased by prescription of nicotine replacement therapies, or of
      buproprion, to aid nicotine withdrawal. Prevention of smoking uptake, especially
      by young people, is much more difficult and has a weaker evidence base. In much
      of Central and Eastern Europe the situation is very severe because of high
      smoking rates and associated diseases and where, although governments are now
      acting with advertising bans and other legislation arising from the Framework
      Convention on Tobacco Control, the healthcare professions themselves have high
      smoking prevalences and a comparative lack of involvement in tobacco cessation
      and prevention practices. In South and South-East Asia, and in emigrant
      communities originating from these areas, the use of oral unsmoked tobacco, the
      chewing of areca nut, and various mixtures of these ingredients in the form of
      betel quids, is highly addictive and carcinogenic to the mouth, pharynx and
      oesophagus. Special and specific efforts are needed for cessation and coping
      strategies in these communities, for which there is a less well-developed
      evidence base.

PMID- 14725650
TI  - Paradigm shifts in medical and dental education: behavioural sciences and
      behavioural medicine.
AB  - Psychosomatic and behavioural medicine have a long tradition in Hungary. In this
      paper, we highlight the possibilities of teaching behavioural medicine and
      behavioural science in the medical and dental curricula, particularly in the
      field of health promotion and prevention. There are a number of possibilities for
      dentists in the fields of behavioural science in both research and health policy.
      There is a need for closer integration of teaching, research and health policy in
      both general medicine and dentistry, and both doctors and dentists must approach
      their patients in a holistic way.

PMID- 14725651
TI  - Attitudes of Hungarian healthcare professional students to tobacco and alcohol.
AB  - Tobacco represents the single most preventable cause of disease and death in the
      world today. There were an estimated 3 million deaths annually at the end of the
      20th century and it has been estimated that this will rise to more than 10
      million by 2030. A disproportionate share of the burden of mortality is already
      being borne in the Russian Federation and the countries of Eastern Europe. For
      example, some of the highest rates worldwide of cigarette consumption and smoking
      prevalence are in the Czech Republic, Hungary and Poland. Cancer is one of the
      major tobacco-related causes of disease and death and Hungary has the highest
      male incidence rates in the world for both oropharyngeal and lung cancer. A
      consequence of this is that the mortality rate of middle-aged (50-60-year-old)
      men in Hungary today is higher today than it was in the 1930s, particularly among
      the lower socioeconomic groups. Of the many different approaches to tobacco
      cessation and control, advice or intervention by healthcare professionals ranks
      high in effectiveness; a recent survey indicated that requests from healthcare
      professionals to quit ranked second in effectiveness after requests by the
      smoker's own family. If healthcare professionals are to play a role in reducing
      death and disease from tobacco related cancers it is necessary to assess the
      attitudes and behaviours among healthcare professional students. Our survey
      assesses perceptions, behaviour and consequences among university students.

PMID- 14725652
TI  - Antismoking education in Czech medical and dental faculties.
AB  - Smoking education has been included in the curricula in all the medical faculties
      of the Czech Republic, although the scope of the education varies. At each of the
      faculties, a member of the staff has been appointed as co-ordinator of smoking
      education. These coordinators promote a sharing of experience and distribution of
      teaching materials. At the majority of faculties, obligatory workshops are held
      for all students to learn about smoking and smoking treatment within the
      framework of preventive medicine. In addition, selected students undertake
      selected studies on smoking and health as part of their research. At the Medical
      Faculty of Masaryk University, Brno, smoking education is included in the
      majority of theoretical and clinical subjects and its effectiveness is repeatedly
      assessed during the 6-year course study by testing the students' knowledge and
      smoking behaviour. The evaluation provides a basis for further modification and
      improvement of the education. Currently, a fundamental transformation of dental
      education is being undertaken in all medical faculties of the Czech Republic.
      These new curricula will benefit from the curriculum of the Medical Faculty, at
      Hradec Kralove, where the changes that were made 5 years ago involve theoretical
      and practical education in the risks of smoking for oral health throughout the 5
      year stomatology courses. Postgraduate medical education involves professional 2
      day seminars for general practitioners on approaches to smoking cessation and
      smoking dependence treatment, and professional materials such as smoking
      cessation guidelines are published in medical and specialist journals.

PMID- 14725653
TI  - Smoking and tobacco control in Poland.
AB  - The study presents information on the use of tobacco and the health consequences
      over the past 20 years in Poland. During this time, Poland has been among the
      countries with the highest cigarette consumption in the world and a
      correspondingly high number of tobacco-related deaths. Data show that nowadays
      about 10 million Polish people smoke; in 1998 average annual, adult, cigarette
      consumption was over 3000. The greatest rate of smoking among men (64%) was
      recorded in 1974 and among women (33%) in 1986. Recently, there has been a
      significant decrease in the rate of smoking among men to 40%, and among women to
      23%. This favourable change has improved health indices such as infant mortality,
      life expectancy, and a lower rate of increase in male deaths from lung cancer.
      Government organizations as well as medical organizations and universities have
      become involved in prevention of smoking and tobacco control in Poland and the
      latest legislation is described.

PMID- 14725654
TI  - Tobacco control and the role of the medical community in the Slovak Republic.
AB  - The Slovak Republic (SR) is located in central Europe and has a population of
      about 5.4 million. Epidemiological data indicate that trends in smoking
      prevalence and incidence of lung cancer have not shown any tendency to decrease
      in the SR. Surveys of Martin residents and of medical students at Comenius
      University provided important data on many aspects of cigarette smoking and
      tobacco dependence and served as a basis for planning and implementing focused
      tobacco control activities at the regional and national levels. The activities
      were focused not only on the Slovak public but also the medical community. With
      assistance from international organizations, Slovak doctors are learning to take
      direct responsibility for treatment and prevention and also a public
      responsibility to influence governmental policies. As a result, tobacco control
      activities in the SR enjoy collaboration between different agencies, community
      participation and personal involvement of health professionals.

PMID- 14725655
TI  - Engineering clinician leadership and success in tobacco control: recommendations
      for policy and practice in Hungary and Central Europe.
AB  - Decades of research and advocacy to control tobacco use and related public-health
      harm have not counterbalanced the tobacco industry's successful stronghold, which
      is ever-increasing in countries with weaker anti-tobacco leadership. Current
      rates of tobacco use and harm in Hungary and other Central European countries
      mark them as some of the industry's greater successes. Following the Behavioural
      Ecological Model, a framework for behavioural and cultural change, this paper
      reviews important ways that dentists, physicians and other healthcare providers
      can counter the tobacco industry's influence on patients, communities, and the
      nation. The analysis includes policies and practices shown to be effective in
      controlling and undermining the tobacco industry, and outlines new policies and
      practices that show promise based on the behavioural change framework. The
      components of an all-encompassing tobacco-control programme are described through
      explicit recommendations for research, practice and policy that are necessary to
      establish a professional and societal culture that extinguishes the influence and
      harm of the tobacco industry in Hungary, Central Europe and developing countries
      worldwide.

PMID- 14725656
TI  - Surgical treatment of nonmelanoma skin cancer in the Medicare population.
AB  - BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common malignancy of white
      populations. Different surgical treatment options can be used to treat these
      tumors, depending on the tumor characteristics and setting. OBJECTIVE: To
      determine how frequently different specialists use the different types of
      surgical options available for the treatment of NMSC using a 1998-1999 sample of
      Medicare claims data. METHODS: Episodes of care of NMSC were identified by
      pathology claims with a diagnosis of NMSC. The surgical interventions performed
      within 7 days before the pathologic diagnosis of NMSC were then analyzed. The
      numbers of patients and the variety of surgical treatments were categorized by
      specialty to include dermatology, general surgery, and plastic surgery. RESULTS:
      Dermatologists managed 82% of the NMSC episodes. Dermatologists used a wider
      range of different treatment options than other specialists and performed 90% of
      the biopsies, 56% of the excisions, 95% of the destructions, and 100% of the Mohs
      micrographic surgeries for NMSC. CONCLUSIONS: Dermatologists identify and manage
      most of the NMSC in the United States and offer patients a broad range of
      surgical options. The use by dermatologists of office-based surgical methods not
      commonly used by other specialists may partially explain previous findings of
      better NMSC outcome by dermatologists. The low level of use of specific surgical
      options by some specialists may indicate the need for greater training/exposure
      to these methods.

PMID- 14725657
TI  - Evaluation of the efficacy of polidocanol in the form of foam compared with
      liquid form in sclerotherapy of the greater saphenous vein: initial results.
AB  - BACKGROUND: Foamed sclerosing agents have been used with enthusiasm by
      phlebologists for more than 5 decades. Any type of varicose veins can and has
      been treated with this technique. Numerous publications have stressed the
      advantages of foamed sclerosing agents on the basis of empiric and experimental
      criteria and have described various individual techniques to prepare foams. Until
      now, however, no comparative study for the treatment of large varicose veins with
      foam or liquid exists. OBJECTIVE: The purpose of this first randomized,
      prospective, multicenter trial was to study the elimination of reflux, the rate
      of recanalization, and possible side effects of foam sclerotherapy (FS) compared
      with conventional liquid sclerotherapy for the greater saphenous vein (GSV).
      METHODS: Eighty-eight patients were randomized into two groups: One group was
      treated with sclerosing foam (45 patients) and the other with sclerosing liquid
      (43 cases). Sclerotherapy was performed with direct puncture of the vessel under
      duplex guidance. The reference sclerosing agent was polidocanol in a 3% solution.
      The foam was prepared using the Double Syringe System (DSS) method. Only one
      injection of 2.0 or 2.5 mL liquid or foam was allowed, depending on the diameter
      of the GSV. Results were assessed according to the protocol. RESULTS: Follow-up
      after 3 weeks showed 84% elimination of reflux in the GSV with DSS foam versus
      40% with liquid sclerosant (P < 0.01). At 6 months, six recanalizations were
      found in the liquid group versus two in the foam group. After 1 year, no
      additional recanalization was observed with either foam or liquid. Longer term
      studies are underway. Side effects did not differ between both groups.
      CONCLUSION: The efficacy of sclerosing foam (DSS) compared with sclerosing liquid
      in therapy of the GSV is superior, a finding that had already gained empirical
      recognition but for which there has not been any clinical evidence to date.

PMID- 14725658
TI  - 532-nm Nd:YAG and 595-nm pulsed dye laser treatment of leg telangiectasia using
      ultralong pulse duration.
AB  - BACKGROUND: Telangiectatic leg veins have been treated using lasers with variable
      success. OBJECTIVE: We aimed to examine the efficacy and tolerability of a 595-nm
      pulsed dye laser (PDL) and a 532-nm Nd:YAG laser using ultralong pulse duration
      to improve leg telangiectasias with a single treatment. METHODS: Ten subjects
      with leg telangiectasias up to 1.0 mm in diameter participated in the study. The
      telangiectatic patch was divided into two approximately equal adjacent areas. The
      first area was treated with a 532-nm Nd:YAG laser at a fluence of 20 J/cm2 and a
      pulse duration of 50 ms using a contact cooling device. The second area was
      treated with a 595-nm PDL at a fluence of 25 J/cm2 and a pulse duration of 40 ms
      using cryogen spray precooling. Each area was treated once only. Photographic
      evaluation was used for an assessment of response. RESULTS: Two of 10 subjects
      had less than 25%, 3 had 25% to 50%, 2 had 50% to 75%, and 3 had more than 75%
      improvement after single treatment with a 532-nm Nd:YAG laser. Similarly, 2 of 10
      subjects had less than 25%, 2 had 25% to 50%, and 6 had 50% to 75% improvement
      with the 595-nm PDL. Hyperpigmentation occurred in one subject treated with the
      532-nm Nd:YAG laser and two subjects treated with the 595-nm PDL. No blistering,
      crusting, hypopigmentation, or scarring were observed. CONCLUSION: Both lasers
      using ultralong pulse width improved leg telangiectasias after a single treatment
      with minimal adverse reactions.

PMID- 14725659
TI  - Evaluation of superficial basal cell carcinomas after treatment with imiquimod 5%
      cream or vehicle for apoptosis and lymphocyte phenotyping.
AB  - OBJECTIVE: To characterize the immune response and the apoptotic pathways that
      result in regression of imiquimod-treated basal cell carcinomas (BCCs). METHODS:
      The trial was conducted as an open-label, matched controlled, nonrandomized
      study. Twelve patients were assigned as either active-treatment patients or
      matched control subjects. After treatment, lesions were excised and stained for
      CD20, CD3, CD4, CD56, bcl-2, bax, caspase-3, and p53. Additionally, a DNA
      fragmentation assay was performed using the terminal deoxynucleotidyltransferase
      mediated dUTP nick-end-labeling method. RESULTS: All vehicle-treated BCCs (six of
      six) had residual tumor compared with four of six imiquimod-treated BCCs. A dense
      mononuclear infiltrate surrounded all of the imiquimod-treated tumors and only
      one of six vehicle-treated BCCs. Staining for CD20, CD3, and CD4 revealed that
      the infiltrate consisted primarily of T-helper lymphocytes; however, a
      significant portion of the cells stained positively for CD56, indicating the
      presence of natural killer cells. Imiquimod-treated BCCs stained more strongly
      for caspase-3 and to a lesser degree p53 as compared with vehicle-treated BCCs.
      No differences were seen in either bax or bcl-2 staining. Minimal apoptosis was
      seen with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end
      labeling assay in either group. CONCLUSION: This study provides evidence that
      imiquimod's antitumorigenic effects are mediated via up regulation of local
      interferon-alpha levels and supports previous work, suggesting that increased
      natural killer cell activity may be an important factors explaining both
      spontaneous regression and IFN-alpha induced regression of BCC.

PMID- 14725660
TI  - Treatment of pseudofolliculitis barbae using the long-pulse Nd:YAG laser on skin
      types V and VI.
AB  - BACKGROUND: Pseudofolliculitis barbae (PFB) is a foreign body inflammatory
      condition that is caused by in-grown hairs of the face and body. An effective
      treatment to alleviate this condition without the risk of side effects has yet to
      be found. OBJECTIVE: The objective of this study was to evaluate the Lyra 1064-nm
      long-pulse ND:YAG laser in the treatment of PFB on skin types V and VI. METHODS:
      Twenty subjects (12 males and 8 females) were given two treatments approximately
      3 to 4 weeks apart and were assessed by objective papule/pustule and hair counts
      at 1, 2, and 3 months after final treatment. Laser treatments with the Lyra
      Nd:YAG laser were applied onto 2x2-cm regions on the upper and lower mandible and
      neck regions. Contralateral controls were used to assess overall effectiveness.
      Subjective evaluations were also obtained from both subjects and investigators.
      Assessments of any abnormal side effects caused by laser treatment, including
      dyspigmentation and/or scarring, were also evaluated. RESULTS: A reduction in the
      quantity of papules/pustules and hairs when compared with baseline data was
      statistically significant for treatment of PFB in the mandibular and neck regions
      at the 1-, 2-, and 3-month follow-up evaluations. Subject evaluations ranged from
      satisfied to very satisfied. Side effects included transient hyperpigmentation,
      transient hypopigmentation, mild erythema, and itching. CONCLUSIONS: The use of
      the 1064-nm long-pulse Nd:YAG laser for the treatment and management of PFB on
      skin types V and VI is both safe and effective, with positive results lasting for
      up for to 3 months after two treatments.

PMID- 14725661
TI  - A pilot study on the treatment of facial rhytids using nonablative 585-nm pulsed
      dye and 532-nm Nd:YAG lasers.
AB  - BACKGROUND: There have been reports of successfully using the pulsed dye laser
      and long-pulse Nd:YAG laser to improve skin wrinkles. OBJECTIVE: To evaluate the
      efficacy of these lasers in the treatment of moderate to severe wrinkles.
      METHODS: Seven subjects had one side of their periorbital wrinkles treated with
      pulsed dye laser (585 nm, 0.45 ms, 2.5 J/cm2, single-pass 10% overlap, three
      treatments at 6 weeks apart). The second part of the study involved using the
      long-pulse Nd:YAG laser (532 nm, 2 ms, 7.0 J/cm2 with cooling, three laser
      passes, three treatments at 6 weeks apart) to treat the contralateral wrinkles in
      five subjects. Pretreatment and posttreatment photographs were taken, and blinded
      assessors were asked to choose the better of the two unlabeled photographs.
      RESULTS: Assessors found that two of the seven subjects had a better
      posttreatment photograph in the pulsed dye laser-treated group. Three of five
      subjects had a better posttreatment photograph in the long-pulse Nd:YAG laser
      treated group. None of the subjects reported any subjective improvements.
      CONCLUSION: Neither the pulsed dye laser nor the long-pulse Nd:YAG laser at the
      previously mentioned parameters produced any improvement in moderate to severe
      facial wrinkles.

PMID- 14725662
TI  - Salicylic acid peels for the treatment of acne vulgaris in Asian patients.
AB  - BACKGROUND: Salicylic acid peels have been introduced as a useful modality in
      acne treatment. Few studies have examined its efficacy and safety, especially in
      darker skin. OBJECTIVE: To assess the efficacy and safety of salicylic acid peels
      as a treatment for acne vulgaris in Asian patients. METHODS: Thirty-five Korean
      patients with facial acne were treated with 30% salicylic acid peels biweekly for
      12 weeks. Lesion counts and Dr. Cunliffe's score were assessed by a blinded
      evaluator. Safety assessments and patient's evaluations were also recorded.
      RESULTS: Both inflammatory and noninflammatory acne lesion counts were decreased
      in proportion to the duration of treatment. Dr. Cunliffe's acne grade was
      statistically significantly decreased after treatment. The side effects were
      tolerable in most cases, and all patients were pleased with their peel results.
      Stratum corneum hydration, skin surface lipid, skin pH, and transepidermal water
      loss were unchanged from baseline levels. CONCLUSION: Salicylic acid peels are an
      effective and safe therapy for acne vulgaris in Asian patients.

PMID- 14725663
TI  - Surgical treatment of facial acne scars based on morphologic classification: a
      Brazilian experience.
AB  - BACKGROUND: Acne scar treatment remains a challenge in the medical literature. It
      is very difficult to compare the efficacy of different therapeutic approaches
      because of the lack of consensus regarding acne scar description and
      classification. OBJECTIVE: To establish a morphologic classification of acne
      scars and to assess the efficacy of different therapeutic options based on scar
      type. METHODS: During an 8-year period, 228 patients were prospectively studied.
      Their acne scars were morphologically classified and customized, staged
      rehabilitation programs were established for each patient. The assessment of
      treatment efficacy was conducted 18 months after the end of treatment and was
      based on patients' and physicians' opinions ranked on a semiquantitative basis as
      percentage of improvement from baseline. RESULTS: Among the 168 patients who
      finished the study, 26 completed three stages of the treatment plan, and 142 were
      submitted to one or two therapeutic stages, depending on lesion types. Eighty-six
      percent of the patients considered the results excellent or good compared with
      76% by the authors and 78% by three independent dermatologic surgeons.
      CONCLUSION: The classification and the staged therapeutic plan for acne scarred
      patients facilitated treatment and improved outcomes and may allow development of
      protocols by comparing results among different authors.

PMID- 14725664
TI  - Needle-guided shave excision with ultrasonographic assistance: a new technique.
AB  - BACKGROUND: A lack of control in the deep margin of shave excision is a drawback
      of this technique. OBJECTIVE: To describe a more precise shaving technique by
      sonography with the use of a fine injector needle as a depth marker. METHODS:
      After having examined the invasion levels of 40 benign skin lesions, a fine
      injector needle was intentionally threaded into the dermis horizontally just
      beneath the required shaving plane. Correct placement of the needle was ensured
      by sonographic examination after possible reinsertion trials. Large lesions
      needed several needles to be inserted. The tissue above the needles was then
      shaved off, whereas the deep dermal layer was protected. RESULTS: Histologic
      examination revealed that 77% of superficial and intermediate-thickness lesions
      were removed totally without disturbing the derma-fat junction. CONCLUSION: The
      needle-guided technique was found to be effective in the control of the deep
      margin of shave excision.

PMID- 14725665
TI  - The use of a "no-touch" technique to reduce the incidence of glove perforation
      during suture needle adjustment.

PMID- 14725666
TI  - Crusotomy: a safe, simple surgical technique to facilitate resection and
      reconstruction of poorly accessible auricular tumors.
AB  - BACKGROUND: Carcinomas of the ear are commonly referred to Mohs surgeons because
      of their tendency for subclinical spread and location in poorly accessible
      anatomic areas. A simple technique, the crusotomy, is described that improves
      access to superior conchal lesions, facilitating resection of these tumors and
      repair of their resultant defects. OBJECTIVE: To describe a surgical technique,
      the crusotomy, which facilitates the resection and repair of poorly accessible
      auricular tumors. METHODS: Five patients with superior conchal tumors are
      presented who underwent crusotomy before resection of their tumors. All patients
      had immediate reconstruction of the resultant defect with either local flaps or
      grafts and were seen in follow-up at 1-week and 1-month intervals. RESULTS:
      Excellent cosmetic results were obtained in all five patients with no
      postoperative complications. CONCLUSION: Crusotomy is a safe, rapid, and simple
      technique that facilitates the resection and repair of poorly accessible
      auricular tumors.

PMID- 14725667
TI  - Idiopathic circumscripta calcinosis cutis of the knee.
AB  - BACKGROUND: Calcinosis cutis, a disease characterized by the presence of calcium
      deposits in the skin, is classified into four types according to etiology:
      dystrophic, metastatic, iatrogenic and idiopathic. The dystrophic form is the
      most common while the idiopathic one is the rarest, but specific incidence and
      frequency data are not available in scientific literature. OBJECTIVE: Calcinosis
      cutis circumscripta is a very rare form of idiopathic calcinosis cutis arising in
      the second half of life. It typically involves the extremities and is associated
      with prior trauma and scleroderma. We dealt with a very rare form of calcinosis
      cutis circumscripta in a healthy patient, for whom surgical excision revealed to
      be an effective and successful treatment. METHODS AND MATERIALS: We present the
      case of a 46-year-old woman affected by idiopathic circumscripta calcinosis cutis
      of the left knee, successfully treated by surgical removal. DISCUSSION: Medical
      and surgical treatment are options to cure calcinosis cutis. Medical therapy is
      not very effective. Surgical excision has shown to be beneficial, as it can
      provide a symptomatic relief. However, since calcinosis cutis limits are not
      always well defined a recurrence of the lesions may occur.

PMID- 14725668
TI  - Granulomatous foreign body reaction against hyaluronic acid: report of a case
      after lip augmentation.
AB  - BACKGROUND: Hyaluronic acid (HA) (Restylane and Hylaform) is becoming more widely
      used for cosmetic procedures such as lip augmentation and treatment of facial
      skin lines, as other products, mainly bovine collagen, have proved allergenic in
      many patients. OBJECTIVE: To report a case of a 48-year-old woman who developed
      discrete nodules in the lips after HA injection for lip augmentation. The
      histologic analysis revealed the presence of a granulomatous reaction surrounding
      a blue amorphous material with the tinctorial features of HA. CONCLUSION: To our
      knowledge, this is the third case of granulomatous body reaction against this
      substance, which was allegedly inert in humans. Although rare, this reaction can
      have important aesthetic implications, and the patients should be informed about
      their risks.

PMID- 14725669
TI  - Metastatic eccrine porocarcinoma: a 5.6-year follow-up study of a patient treated
      with a combined therapeutic protocol.
AB  - BACKGROUND: Metastatic eccrine porocarcinoma (EP) is an uncommon, malignant, and
      potentially lethal neoplasm that arises from the eccrine sweat glands. OBJECTIVE:
      To present the 5.6-year follow-up study of a male patient with metastatic EP,
      highlighting the widespread cutaneous involvement and the response to the
      treatment carried out. METHODS: We describe the evolution of the tumor and the
      combined therapy carried out and review the treatments employed in previously
      reported cases, comparing them with ours. RESULTS: The patient developed multiple
      cutaneous and regional lymph node metastases 15 months after surgical excision of
      the primary tumor. He was treated with prophylactic lymphadenectomy,
      radiotherapy, and oral isotretinoin, subsequently substituted by tegafur. We have
      not found evidence of distant metastases after a 5.6-year follow-up. CONCLUSIONS:
      The optimum treatment for metastatic EP is not standardized, and the results
      obtained to date were generally poor. In this context, we consider it of interest
      to highlight the response of our patient to the therapeutic regime employed,
      which may be advantageous in future cases of this rare tumor.

PMID- 14725670
TI  - Multiple pigmented basal cell carcinomas arising in the normal-appearing skin
      after radiotherapy for carcinoma of the cervix.
AB  - BACKGROUND: The most frequent radiation-induced skin cancers are basal cell
      carcinomas (BCCs), and in many cases, they may occur subsequent to tinea capitis,
      hypertrophic tonsillitis, acne vulgaris, atopic dermatitis, and hyperthyroidosis.
      BCCs occurring after radiotherapy for carcinoma of the cervix are extremely rare.
      OBJECTIVE: To describe a case of multiple pigmented BCCs caused by radiotherapy
      for carcinoma of the cervix. RESULTS: A 76-year-old female presented with four
      tumoral lesions within a previously irradiated area. The patient had undergone
      radiation therapy for cervical cancer 38 years before. All of the lesions were
      totally excised and histopathologically diagnosed as BCCs. There was no apparent
      gross chronic radiodermatitis around the lesions, but characteristic
      histopathologic alterations of radiodermatitis were observed. No new tumors were
      observed to date. CONCLUSION: The latent period for radiation-induced skin cancer
      is generally very long; secondary skin cancers can develop very late in life.
      Patients previously treated with radiation therapy require careful follow-up for
      life.

PMID- 14725671
TI  - Full-face carbon dioxide laser resurfacing in the management of a patient with
      the nevoid basal cell carcinoma syndrome.
AB  - BACKGROUND: Multiple surgical procedures are often a source of discomfort, pain,
      and disfigurement for patients with the nevoid basal cell carcinoma syndrome
      (NBCCS). OBJECTIVE: The patient with NBCCS had approximately 45 identifiable
      basal cell carcinomas on her face. Multiple Mohs surgeries were performed to
      remove the largest tumors. A tumor-free plane was not achieved in several lesions
      despite removal of multiple tissue layers. The treatment of the remaining tumors
      presented a significant challenge. METHODS: Full-face CO2 laser resurfacing was
      performed after curettage and local laser ablation of all visible tumors.
      RESULTS: The patient healed well postoperatively. She developed six basal cell
      carcinomas on her face during the 10-month follow-up period. These were easily
      treated with Mohs surgery and imiquimod cream. CONCLUSION: CO2 laser resurfacing
      is a useful surgical modality for treatment of multiple facial basal cell
      carcinomas in the patients with NBCCS. It allows treatment of all the facial
      lesions in a single session and minimizes suffering resulting from repeated
      surgical procedures. Additionally, the layer of skin damaged by ultraviolet
      radiation is removed, allowing for easier management after resurfacing.

PMID- 14725672
TI  - Disseminated squamous cell carcinoma of the skin.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) accounts for a large proportion of
      nonmelanoma skin cancers. It may appear mainly on the skin and the mucous
      membranes; however, it may also appear on any part of the body. The tumor
      originates from atypical keratinocytes. This tumor, which can be locally
      destructive, has a metastasis rate of 5% to 10%. OBJECTIVE: To present a patient
      with disseminated primary SCC of the skin. METHODS: In this report, we present a
      unique case of disseminated SCC that is thought to be primary. As far as we know,
      the patient neither had any syndrome or a disease predisposing to SCC nor was
      exposed to toxic substances or ionized radiation. The disease progressed in a
      very short period. To our knowledge, there has not so far been a case of
      disseminated primary SCC. The patient was inoperable when he presented to our
      clinic. RESULTS: Chemotherapy was instituted in the Department of Medical
      Oncology; unfortunately, the patient died while on the therapy. CONCLUSION: An
      original case of disseminated SCC of the skin is presented.

PMID- 14725673
TI  - Glomangioma of the hip.
AB  - BACKGROUND: Glomus tumors may occur in any region of the body, but they are very
      rare in the hip. OBJECTIVE: To present the eighth reported case of a glomus tumor
      of the hip up to date. METHODS: This is a case report and a literature review.
      RESULTS: A 68-year-old man presented with severe pain and tenderness in the right
      hip, especially on palpation and in the sitting position. On physical
      examination, there was a soft palpable subcutaneous mass and severe tenderness in
      the right hip. Ultrasound revealed a hypervascular subdermal mass that was 2 cm
      in diameter. The lesion arose from the dermis and extended into the subcutaneous
      tissue. It was totally excised under local anesthesia. The histopathologic
      diagnosis was a glomangioma. The patient has been symptom free in the 2 months of
      follow-up. CONCLUSIONS: Glomus tumors should be kept in mind in the differential
      diagnosis of painful subdermal mass. Surgical excision of the lesion with a
      sufficient margin of surrounding normal tissue not only achieves the exact
      diagnosis but also results in adequate treatment. In case of the presence of
      malignant features, a wide excision is needed with a close follow-up of patient
      for regional or distant metastases.

PMID- 14725674
TI  - Appetite regulation: from the gut to the hypothalamus.

PMID- 14725676
TI  - Standard and low-dose IGF-I generation tests and spontaneous growth hormone
      secretion in children with idiopathic short stature.
AB  - OBJECTIVE: Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity
      (GHI), have been reported in some patients with idiopathic short stature (ISS).
      The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in
      subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in
      ISS by performing standard and novel low-dose IGFGTs together with determination
      of spontaneous GH secretion. PATIENTS AND METHODS: Twenty-one (17 male)
      prepubertal children with ISS, mean age 8.3 years (4.5-12.2), mean height -3.48
      SD (-5.40 to -1.79), mean peak GH to provocation with glucagon/clonidine 32.3
      mU/l (14.1-66.0) were studied. Serum IGF-I and IGFBP-3 levels were measured
      during standard (GH 0.033 mg/kg/day x 4) and low (GH 0.011 mg/kg/day x 4) dose
      IGFGTs at 0, 12, 36 and 84 h. The low-dose IGFGT was performed in seven naive GH
      deficient patients (4 male), mean age 8.5 years (range 4.1-11.1). Determination
      of spontaneous 24-h GH secretion was performed in the 21 ISS patients. RESULTS:
      Basal IGF-I and IGFBP-3 standard deviation scores (SDS) in ISS patients were 
      1.39 (-2.4-1.16) and -0.45 (-1.13-0.38), respectively, IGF-I being lower than
      IGFBP-3 (P < 0.0001). IGF-I increased in the standard IGFGT at 12 h (P < 0.005),
      36 h (P < 0.001) and 84 h (P < 0.001); maximal increment 1.54 (-0.32-3.48), and
      in the low-dose test at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.005);
      maximal increment 0.53 (0.08 to -1.23). IGFBP-3 SDS increased in the standard
      IGFGT at 36 h (P < 0.01) and 84 h (P < 0.001); maximal increment 0.72 (-0.44
      1.96), and in the low-dose test at 84 h (P < 0.005); maximal increment 0.33 (
      0.08-0.87). Five/19 patients with an IGF-I response > 2 x coefficient of
      variation (CV) of assay in the standard test failed to respond in the low-dose
      test, suggestive of mild GHI. In GH-deficient patients, IGF-I increased at each
      time point (P < 0.05) and IGFBP-3 at 36 h (P < 0.05). Mean GH secretion,
      expressed in SDS, compared with 66 normal stature controls was: basal GH -0.48 (
      0.84-0.93), height of GH peaks compared with zero -0.36 (-1.26-1.51) (both P <
      0.05), total GH secretion -0.76 (-1.22-0.42), total GH secretion above baseline 
      0.67 (-1.21-0.94) (both P < 0.01). CONCLUSIONS: In children with ISS, basal IGF-I
      and IGFBP-3 SDS values were below the mean, IGF-I showing a greater response in
      both IGFGTs. In the standard IGFGT, the IGF-I increase at 36 h was equal to that
      at 84 h. The low-dose IGFGT, in combination with the standard test, may identify
      patients with mild GHI.

PMID- 14725677
TI  - Successful treatment of childhood-onset Cushing's disease is associated with
      persistent reduction in growth hormone secretion.
AB  - OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected
      children commonly fail to achieve predicted adult height. Hypercortisolaemia
      results in reduced GH secretion and GH-deficiency may persist or demonstrate
      delayed recovery after successful treatment of CD in adults. Whether recovery of
      spontaneous GH secretion occurs following treatment of childhood CD has yet to be
      established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH
      status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had
      undergone successful treatment of CD that occurred prior to the completion of
      linear growth. Each underwent transsphenoidal hypophysectomy, resulting in
      satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six
      patients (46%) received fractionated external beam irradiation (4500 Gy). At the
      time of GH assessment, circadian dynamics of cortisol were normal in eight
      patients and five were receiving titrated glucocorticoid replacement.
      MEASUREMENTS: GH status was assessed using the peak response to a provocative
      stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia
      (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13.
      Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal
      response as > 30 mU/l. Intermediate values were taken to represent subnormal GH
      status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE)
      following successful treatment (range 9-108 months). RESULTS: Using these
      criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a
      normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those
      with multiple pituitary hormone deficiencies were most likely to have lower peak
      GH levels, but there was no clear effect of pituitary irradiation or relationship
      between duration post cure and peak GH response. CONCLUSION: GH-deficiency is
      common and may persist for many years following successful treatment of CD prior
      to completion of linear growth. External radiotherapy does not necessarily result
      in severe GH-deficiency in the short term. Assessment of GH status and
      consideration of GH treatment should be considered following treatment of CD in
      childhood and adolescence in order to maximize the opportunities to achieve a
      satisfactory final adult height. In those with subnormal GH responses, continued
      assessment is necessary to determine whether the GH axis subsequently recovers or
      if these patients develop features of the adult GH-deficiency syndrome.

PMID- 14725678
TI  - Longitudinal changes of lumbar bone mineral density (BMD) in patients with GH
      deficiency after discontinuation of treatment at final height; timing and peak
      values for lumbar BMD.
AB  - OBJECTIVE: GH treatment has an important role in the acquisition of bone mass in
      children and adolescents with GH deficiency (GHD). However, there is no
      information concerning the timing and value of peak bone mass in treated patients
      with GHD. In adolescents with GHD we longitudinally measured lumbar bone mineral
      density (BMD) after discontinuation of GH treatment at final height until they
      achieved lumbar peak BMD (pBMD). Moreover, the changes of lumbar BMD after the
      attainment of the peak were assessed for a period of 2 years. The results of
      patients were compared with those obtained in age- and sex-matched healthy
      controls. PATIENTS AND MEASUREMENTS: Lumbar BMDarea [bone mineral content (BMC)
      corrected by the vertebral surface area scanned] and lumbar BMDvolume (BMC
      corrected by vertebral volume estimated by a mathematical model), by dual energy
      X-ray absorptiometry, were assessed in 16 patients (nine males, seven females;
      aged 14.9-18.8 years) with isolated GHD and 157 healthy subjects (78 males, aged
      16.2-24.9 years; 79 females, aged 14.1-22.8 years) as controls. In patients,
      lumbar BMDarea and lumbar BMDvolume were measured at final height and
      approximately every year up to 21-24 years and 19-22 years in males and females,
      respectively; BMD values of the patients were plotted on the reference curves for
      age and sex obtained in controls. RESULTS: At final height, seven male (78%) and
      five female (71%) patients had a value for lumbar BMDarea below 2SD of normal
      mean, whereas all patients had a value of lumbar BMDvolume between 0 and -2SD of
      normal mean. In patients, lumbar pBMDarea and lumbar pBMDvolume were achieved
      approximately 1-3 years after final height. The timing of lumbar pBMDarea and
      lumbar pBMDvolume was significantly (P < 0.0001) delayed in patients in
      comparison with controls (pBMDarea: males, 19.8 +/- 0.6 years and 18.4 +/- 0.6
      years; females, 18.0 +/- 0.3 years and 16.7 +/- 0.6 years, respectively;
      pBMDvolume: males, 19.8 +/- 0.7 years and 18.6 +/- 0.6 years; females, 18.0 +/-
      0.4 years and 16.7 +/- 0.6 years, respectively). In addition, mean values for
      lumbar pBMDarea and lumbar pBMDvolume were significantly (P < 0.01 to P < 0.0001)
      reduced in patients compared with controls (pBMDarea: males, 1.129 +/- 0.055
      g/cm2 and 1.225 +/- 0.048 g/cm2; females, 1.122 +/- 0.053 g/cm2 and 1.227 +/-
      0.060 g/cm2, respectively; pBMDvolume: males, 0.326 +/- 0.010 g/cm3 and 0.352 +/-
      0.036 g/cm3; females, 0.348 +/- 0.010 g/cm3 and 0.388 +/- 0.039 g/cm3,
      respectively). In patients, mean values of lumbar BMDvolume declined
      significantly (P < 0.03 to P < 0.01) 2 years after its peak. At any rate, mean
      values of lumbar BMDarea and lumbar BMDvolume of patients one and two years after
      their peak remained significantly lower (P < 0.01 to P < 0.0001) than those of
      controls. CONCLUSIONS: The results show that treated adolescents with GHD have an
      increase of lumbar BMDarea and lumbar BMDvolume after discontinuation of GH
      treatment at final height, but they have delayed timing and reduced mean values
      of lumbar pBMDarea and lumbar pBMDvolume in comparison with controls. In
      patients, mean values of lumbar BMDvolume declined 2 years after its peak.
      Although the number of the patients was small, the results seem to indicate that
      GH has a role in the acquisition of lumbar BMD after final height in patients
      with GHD, suggesting that GH treatment should be continued up to the achievement
      of lumbar pBMD.

PMID- 14725679
TI  - Evaluation of the reproducibility of the GHRH plus GHRP-6 test of growth hormone
      reserve in adults.
AB  - BACKGROUND: The diagnosis of GH deficiency (GHD) is controversial, relying on GH
      secretion elicited by the provocative tests of GH reserve. However, the
      performance of most of the tests in use have not been evaluated rigorously. The
      repeatability of a test is a prerequisite before evaluating its diagnostic
      capability. OBJECTIVE: The combined administration of GH-releasing hormone (GHRH)
      and GH-releasing hexapeptide (GHRP-6) is an efficacious test of GH reserve in
      adults, and the target of this work was to evaluate its reproducibility. METHODS:
      Seventeen healthy subjects were challenged with GHRH plus GHRP-6 (1 micro g/kg
      i.v.). All subjects underwent four tests on different days separated by at least
      2 months. GH peaks were evaluated by several mathematical analyses of
      reproducibility. RESULTS: As a group, the subjects showed high reproducibility
      after the four tests, with GH peaks of 46.0 +/- 5.1; 48.4 +/- 6.4; 50.1 +/- 5.4
      and 52.9 +/- 5.8 micro g/l, respectively (1 micro g/l = 3 mU/l). Individually
      analysed, the reproducibility was good, and the regression analysis showed a
      correlation between tests 1 and 2 of R = 0.729, P < 0.0009, between tests 1 and 3
      of R = 0.710, P < 0.001, and between tests 1 and 4 of R = 0.683, P < 0.002. Under
      mathematical analysis, the multiple correlation coefficient analysis, analysis of
      variance (anova) with repeated measurements, repeatability index, the simplest
      coefficient of variation and the intraclass correlation coefficient (ICC) all
      unambiguously showed that the GHRH + GHRP-6 test was reproducible. Furthermore,
      the repeated tests did not alter the biochemical diagnosis of the subjects, with
      absence of false-positive values. CONCLUSIONS: The GHRH + GHRP-6 test of GH
      reserve is reproducible in adult subjects.

PMID- 14725680
TI  - Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH
      independent macronodular adrenocortical hyperplasia.
AB  - OBJECTIVE: Vasopressin (AVP) is reported to be an important factor for regulating
      cortisol secretion in patients with Cushing's syndrome due to ACTH-independent
      macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been
      several case reports of subclinical Cushing's syndrome due to AIMAH, in which the
      pathophysiological role of AVP has been unknown. The aim was to conduct an
      extensive investigation of AVP in the autonomous secretion of cortisol in
      subclinical Cushing's syndrome due to AIMAH. PATIENTS AND MEASUREMENTS: Five
      cases of AIMAH with subclinical Cushing's syndrome underwent prospective study
      including physical examination, imaging (MRI, CT and 131I-adosterol scintigraphy)
      and endocrinological evaluation that comprised basal plasma cortisol levels and
      urinary excretions of steroid metabolites, a dexamethasone suppression test and
      an AVP stimulation test. In case 1, left adrenalectomy was performed and the
      pathological diagnosis of AIMAH was established. An in vitro experiment using the
      cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and
      expression of the V1-AVP receptor, mRNA by RT-PCR. RESULTS: All five cases were
      discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT
      revealed large multinodular lesions in both adrenal glands, which showed positive
      uptake on 131I-adosterol scintigraphy. Although the basal values of plasma
      cortisol and urinary excretions of steroid metabolites were within normal limits,
      autonomous secretion of cortisol was assumed to occur because of lack of
      suppression during dexamethasone suppression. The five patients had no overt
      signs of Cushing's syndrome, and they were therefore diagnosed with subclinical
      Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol
      secretion in vivo, whereas desmopressin acetate failed to affect cortisol
      secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH
      adrenal cells, but this secretion had no relationship with cAMP production. In
      addition, over-expression of V1-AVP receptor mRNA in AIMAH tissue was determined
      by RT-PCR. CONCLUSION: Patients with subclinical Cushing's syndrome due to AIMAH
      commonly exhibit cortisol responsiveness to AVP, and this is probably mediated
      through activation of overexpressed V1-AVP receptors.

PMID- 14725681
TI  - Size at birth, the metabolic syndrome and 24-h salivary cortisol profile.
AB  - OBJECTIVE: Individual variation in hypothalamic-pituitary-adrenal axis (HPAA)
      function has been suggested to be important in linking small size at birth with
      adult cardiovascular disease and its risk factors, in particular the metabolic
      syndrome. Human studies have, however, so far only been performed in clinic
      settings, and their results have not been consistent. Our aim was to assess
      whether HPAA activity in everyday living circumstances is related to the
      metabolic syndrome and size at birth. DESIGN: Clinical birth cohort study.
      SUBJECTS: A total of 151 women born between 1924 and 1933 in Helsinki, Finland,
      with measurements at birth recorded. The subjects had previously undergone
      detailed clinical examinations including fasting cortisol measurement and 1 micro
      g ACTH1-24 and overnight 0.25 mg dexamethasone tests. MEASUREMENTS: Salivary
      cortisol concentration was measured during a normal 24-h period: at awakening, 15
      and 30 min thereafter, at 12.00 h, 17.00 h and 22.00 h and the following morning.
      In addition, the following summary variables were calculated: awakening response
      (mean of the three awakening measurements), mean of all individual measurements,
      and mean, SD and contrast (a measure of blunted diurnal variability, calculated
      as mean of morning minus mean of 1200, 1700 and 2200) of all individual z scores.
      RESULTS: Salivary cortisol awakening response was correlated with serum fasting
      (r = 0.17; P = 0.04), ACTH1-24-stimulated (r = 0.32; P < 0.0001), and
      dexamethasone-suppressed (r = 0.29; P = 0.0004) cortisol concentrations. However,
      no salivary cortisol measurement was associated with any component of the
      metabolic syndrome (waist circumference, serum triglyceride, HDL cholesterol or
      glucose concentration, or blood pressure). Moreover, no correlation was observed
      between salivary cortisol and weight, length, ponderal index, or gestational age
      at birth. CONCLUSIONS: In elderly women, cortisol concentrations in an everyday
      environment do not appear to be associated with the metabolic syndrome or size at
      birth. We propose that detecting relationships between HPAA function, prenatal
      events and adult disease might require a test involving HPAA stimulation.

PMID- 14725682
TI  - High leptin levels in women developing postpartum thyroiditis.
AB  - BACKGROUND: There is experimental evidence that leptin is required for the
      development of T helper 1 (Th1)-mediated autoimmune diseases. However, to our
      knowledge, there are no studies demonstrating such a role in human autoimmune
      thyroid disease. OBJECTIVE: In the present study we have retrospectively examined
      patients developing postpartum thyroiditis (PPT), as a model of autoimmune
      disease, for changes in serum leptin levels during the postpartum period.
      MATERIALS AND METHODS: The study group included 61 women in the first month
      postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty
      TPOAb-negative (-ve), age and body mass index (BMI)-matched, postpartum women
      were enrolled as the control group. All subjects were evaluated for BMI, serum
      leptin values, thyroid function [serum free-triiodiothyronine (FT3), free
      thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement
      activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks' postpartum. During the
      postpartum period, 32 of 61 TPOAb+ve women (52.4%) showed one or more episodes of
      thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women
      remained euthyroid throughout the study period (PPTE group). None of the control
      group developed thyroid dysfunction. RESULTS: Four weeks postpartum, TPOAb+ve
      women showed higher serum leptin values than TPOAb-ve women, despite comparable
      BMI. At this time, PPTE and PPTD patients showed no significant differences in
      leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD
      patients maintained significantly higher leptin values and leptin/BMI ratio
      compared to the healthy women. In PPTE women, however, a significant reduction in
      leptin levels and leptin/BMI ratio was seen at 12 weeks' postpartum. This
      decrease was transient and correlated negatively with the variation in C3 index
      at the same time. No significant correlation was found between serum leptin
      variations and FT4 or TSH levels. CONCLUSIONS: This study has demonstrated that
      women developing postpartum thyroiditis have higher leptin values compared to the
      healthy women. The higher levels were maintained for 6 months postpartum. This
      result would suggest an involvement of leptin in the pathogenesis of postpartum
      thyroid disease, although further studies are needed to characterize the
      reciprocal effects of leptin, immune system and thyroid hormones during the
      course of this disease.

PMID- 14725683
TI  - Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK
      ligand serum levels in healthy young women.
AB  - OBJECTIVE: Osteoprotegerin (OPG) represents a secreted cytokine which regulates
      bone mass by blocking receptor activator of nuclear factor-kappaB ligand (RANKL),
      the principal regulator of osteoclast function. In vitro, OPG production is
      upregulated by oestrogens in osteoblastic lineage cells, a mechanism that has
      been discussed as a protective paracrine mechanism of oestrogens on the skeleton.
      To define the effects of oestrogens on the RANKL/OPG system in vivo, we evaluated
      OPG and both free and total soluble RANKL (sRANKL) serum levels in healthy young
      women with or without oral contraceptives. DESIGN AND PATIENTS: Serum levels of
      OPG and sRANKL were prospectively assessed in a cohort of healthy young women
      with (n = 30) or without (n = 25) combined oestrogen-progestin-based oral
      contraceptives. MEASUREMENTS: OPG, total and free sRANKL serum levels were
      determined by enzyme-linked immunosorbent assays (ELISA). RESULTS: In women using
      oral contraceptives, OPG serum levels were significantly higher (2.71 +/- 1.42
      pmol/l) compared to nonusers (1.35 +/- 1.02 pmol/l; P = 0.0003), whereas free (P
      = 0.55) and total (P = 0.24) sRANKL serum levels did not differ between both
      groups. This resulted in an increased OPG/free sRANKL ratio (P = 0.02) in women
      on oral contraceptives. During the ovarian cycle, OPG (P = 0.22) and free sRANKL
      (P = 0.99) serum levels remained unchanged in women without oral contraceptives
      (n = 19), while total sRANKL levels were higher in the follicular than in the
      luteal phase (P = 0.02). CONCLUSIONS: Intake of oral contraceptives is associated
      with increased OPG serum levels, but not sRANKL levels, resulting in a higher
      OPG/sRANKL ratio. This may contribute to the positive effects of oral
      contraceptives on the skeleton.

PMID- 14725684
TI  - Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or
      compensated hypothyroidism with probable hemizygosity for inactivating mutations
      of the TSH receptor.
AB  - OBJECTIVE: We wished to ascertain whether mutations in the TSH receptor (TSHR)
      gene were present in two siblings with congenital hypothyroidism with no parental
      consanguinity. DESIGN: The pituitary-thyroid axis and thyroid gland morphology
      were investigated in both affected siblings and their parents. The TSHR gene was
      analysed in each subject. MEASUREMENTS: Basal thyroid function together with
      circulating thyroglobulin levels were measured in each subject. In addition, a
      TRH stimulation test was undertaken in each parent. All family members underwent
      thyroid ultrasonography. The TSHR gene was amplified from genomic DNA using the
      polymerase chain reaction and receptor mutations were identified by sequence
      analysis. RESULTS: Two siblings were diagnosed with severe congenital
      hypothyroidism (total T4 19-21 nmol/l, TSH 160-230 mU/l on neonatal screening).
      Although radioiodine scanning showed no tracer uptake and ultrasound imaging in
      both individuals failed to demonstrate thyroid tissue, suggesting complete
      athyreosis, circulating thyroglobulin levels were measurable. The thyroid status
      of the parents was discordant: in the father, baseline thyroid function (FT4 13
      pmol/l, TSH 4 mU/l), the peak TSH level after TRH stimulation (30 mU/l) were
      normal and he exhibited an appropriate rise in circulating thyroid hormones in
      response to the elevated TSH; in contrast, in the mother, baseline thyroid
      function was abnormal (FT4 10 pmol/l, TSH 15 mU/l), the TSH response to TRH was
      exaggerated (110 mU/l), with no subsequent rise in circulating thyroid hormones.
      An eutopic, slightly hypoplastic thyroid gland was visualized on ultrasonography
      in the mother and her thyroid antibody status was negative. Both children were
      compound heterozygotes for missense (alanine to threonine at codon 553, A553T)
      and premature stop (tryptophan at codon 546, W546X) mutations in the fourth
      transmembrane domain of the TSH receptor. The mother and father were heterozygous
      for W546X and A553T mutations, respectively. Each mutation is known to abolish
      the function or cellular surface expression of the TSH receptor. CONCLUSIONS:
      Inactivating mutations in the TSH receptor can be associated with severe TSH
      resistance presenting as congenital hypothyroidism with apparent athyreosis. Our
      observations also suggest that heterozygosity for an inactivating TSHR mutation
      may be associated with compensated hypothyroidism and thyroid hypoplasia.

PMID- 14725685
TI  - Hypertriglyceridaemia in Alstrom's syndrome: causes and associations in 37 cases.
AB  - OBJECTIVE: To document frequency of severe hypertriglyceridaemia in Alstrom's
      syndrome (AS) and its relationship to hepatic and renal function, glycaemia and
      insulin resistance. PATIENTS AND METHODS: Thirty-seven subjects with AS aged 5-35
      years, 51% male, were assessed at multidisciplinary clinics in Canada, UK and
      Italy. Diagnostic criteria were: severe cone/rod dystrophy leading to severe
      visual impairment in early childhood, sensorineural deafness, moderate overall
      obesity and normal intelligence. Three patients were treated with thyroxine for
      primary hypothyroidism and one female patient for secondary amenorrhoea with 20
      micro g ethinyloestradial combined oral contraceptive. Two male patients were
      receiving monthly intramuscular testosterone enanthate for secondary
      hypogonadism. Fasting bloods were taken for serum insulin, serum glucose, serum
      triglycerides, hepatic and renal function and glycosylated Hb. Triglyceride
      levels > 8 mmol/l and fasting serum insulin levels > 16 microunits/ml were
      considered to represent severe hypertriglyceridaemia and severe insulin
      resistance, respectively. All subjects with (23) hypertriglyceridaemia also had
      high insulin resistance, as measured by HOMA modelling. However, there was no
      significant correlation between log tyriglyceride and log serum insulin or HOMA
      in the whole group (P = 0.2 and 0.14, respectively). There was no clear
      relationship between serum triglyceride levels and age, body mass index (BMI),
      hepatic or renal impairment or glycaemia. CONCLUSION: The first overview of serum
      triglyceride levels in a significant number of reported cases of Alstrom Syndrome
      shows an overlap between severe hypertriglyceridaemia and severe hyperinsulinism,
      but not a direct correlation between the two nor with insulin resistance measured
      by HOMA. Triglyceride levels were not related to glycaemia, hepatic or renal
      dysfunction.

PMID- 14725686
TI  - Oestrogen receptor alpha genotype, and interactions between vitamin D receptor
      and transforming growth factor-beta1 genotypes are associated with quantitative
      calcaneal ultrasound in postmenopausal women.
AB  - OBJECTIVE: Quantitative ultrasound (QUS) of bone is a new radiation-free, low
      cost method that measures both bone mass and quality. We investigated
      associations between QUS parameters and polymorphisms of vitamin D receptor
      (VDR), oestrogen receptor alpha (ERalpha) and transforming growth factor-beta1
      (TGF-beta1) genes in postmenopausal women residing in a community. DESIGN: QUS
      and anthropometric characteristics were measured in postmenopausal women, and
      compared with regard to the VDR, ERalpha and TGF-beta1 genotypes. PATIENTS: Among
      the 552 women who participated in the population-based Chung-Up osteoporosis
      prevalence study, 206 postmenopausal women, aged 60-69 years, were included.
      MEASUREMENTS: Broadband ultrasound attenuation (BUA) and speed of sound (SOS)
      were measured at the left calcaneus using QUS measurement of bone, and a
      stiffness index (SI) was calculated. We determined the BsmI and FokI
      polymorphisms of VDR gene and the XbaI and PvuII polymorphisms of ERalpha gene
      using the polymerase chain reaction-restriction fragment length polymorphism
      method, and Tau29 --> C polymorphism of TGF-beta1 gene using an allele-specific
      polymerase chain reaction assay. RESULTS: The XbaI polymorphism of ERalpha gene
      was significantly associated with SI (T-score) and BUA (P = 0.040 and P = 0.024,
      respectively). There were no significant differences in any QUS parameters among
      the genotypes of VDR and TGF-beta1. However, significant genetic interactions
      between the VDR and TGF-beta1 genotypes, were noted (P = 0.017 for SI and P =
      0.028 for BUA between the BsmI and Tau29 --> C polymorphisms; P = 0.038 for SI
      and P = 0.035 for BUA between the FokI and T29 --> C polymorphisms). The combined
      genotypes between the BsmI and T29 --> C polymorphisms or between the FokI and
      T29 --> C polymorphisms, were significantly associated with the QUS parameters.
      CONCLUSIONS: This study indicates that the XbaI polymorphism of ERalpha gene may
      influence the Quantitative ultrasound parameters in postmenopausal women, and
      suggests the need for further investigations about the interactions between the
      VDR and TGF-beta1 genes.

PMID- 14725687
TI  - Effect of flutamide and metformin administered alone or in combination in dieting
      obese women with polycystic ovary syndrome.
AB  - BACKGROUND: Hyperandrogenism, hyperinsulinaemia and obesity play a key and
      coordinating roles in the pathogenesis of polycystic ovary syndrome (PCOS),
      contributing in different ways to the clinical expression of the syndrome. Weight
      loss is beneficial, but the additional administration of insulin-lowering drugs,
      such as metformin, and antiandrogens may produce further benefits, due to their
      different spectrum of action. The effects of long-term metformin and flutamide,
      an antiandrogen drug, added alone or in combination with a low-calorie diet, on
      body weight and fat distribution, androgens, metabolic parameters and clinical
      status in obese women with PCOS were investigated. METHODS: Forty obese women
      with PCOS were enrolled in the study. After a 1-month diet, according to single
      blind design, the patients were allocated to treatment with placebo, metformin
      (850 mg/orally, twice daily), flutamide (250 mg/orally, twice daily) or metformin
      (850 mg/orally, twice daily) + flutamide (250 mg/orally, twice daily) for the
      following 6 months, while continuing hypocaloric dieting. At baseline and at the
      end of the study, sex hormone, SHBG, lipid, insulin and insulin sensitivity
      determinations were evaluated. At the same time, clinical parameters such as
      anthropometry, total (TAT), visceral (VAT) and subcutaneous (SAT) adipose tissue,
      hirsutism and menses were also measured. RESULTS: We found that, in obese PCOS
      women, following a hypocaloric diet the addition of metformin, flutamide or the
      combined metformin + flutamide treatment had some specific additional favourable
      effects with respect to the low-calorie diet alone. In particular, flutamide
      treatment seemed to add a significant effect in decreasing visceral fat,
      androstenedione, DHEA-S, total and low density lipoprotein (LDL) cholesterol and
      in improving hirsutism. Conversely, metformin had significant benefits on the
      menstrual status. The two drugs showed an additive effect in reducing
      testosterone concentrations and a synergistic effect in increasing high density
      lipoprotein (HDL) cholesterol and SHBG levels. Improvement of insulin sensitivity
      and hyperinsulinaemia appeared to depend on hypocaloric diet, without any further
      significant effect of the pharmacological treatments, either alone or in
      combination. CONCLUSIONS: We conclude that, in obese PCOS women, following a
      hypocaloric diet the addition of metformin, flutamide or the combined metformin +
      flutamide treatment appears to have a more favourable outcome on body fat
      distribution, androgens, lipids, hirsutism and menses. However, our data
      emphasize the dominant role of hypocaloric dieting in improving insulin
      resistance and hyperinsulinaemia. Therefore, this study provides a rationale for
      specifically targeting different therapeutical options for PCOS according to the
      required outcomes.

PMID- 14725688
TI  - Predictors of intellectual outcome in a cohort of Brazilian children with
      congenital hypothyroidism.
AB  - OBJECTIVE: To identify predictors of intellectual development in a cohort of
      children with permanent primary congenital hypothyroidism. DESIGN: Cohort study
      with intellectual development as the outcome. PATIENTS AND MEASUREMENTS: Thirty
      one consecutive newborns with permanent primary congenital hypothyroidism
      diagnosed by a screening programme were recruited from the outpatient clinic of a
      district hospital and underwent psychometric evaluation with the Wechsler
      Intelligence Scales after a minimum follow-up of 4 years. RESULTS: Eight of the
      31 patients (25.8%) presented impaired intellectual development (full-scale
      intellectual quotient < 85), and one of them presented mental deficiency (full
      scale intellectual quotient </= 69). The following were associated with worse
      prognosis: initial serum T4 levels </= 32.18 nmol/l, treatment beginning after 30
      days of age, fewer than seven clinic visits during the first year of life, living
      in rural areas, nonintellectual parental occupation and little parental
      schooling. In a multiple regression analysis, only maternal schooling (B = 0.401;
      beta coefficient = 13.053, P = 0.063), number of clinic visits during the first
      year of life (B = 0.382; beta coefficient = 4.145, P = 0.047) and initial serum
      T4 (B = 0.287; beta coefficient = 1.336, P = 0.089) remained significantly
      associated with full-scale intelligence quotient scores. CONCLUSION: Maternal
      schooling, number of visits during the first year of life and baseline T4 levels
      were the main predictors of cognitive outcome in this cohort of patients.

PMID- 14725689
TI  - Adiponectin, hepatocellular dysfunction and insulin sensitivity.
AB  - OBJECTIVE: Insulin resistance plays a major aetiological role in the development
      of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and
      also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin
      resistance and liver damage, we wished to study whether low circulating
      adiponectin would be associated with higher serum concentrations of liver enzymes
      in healthy subjects. DESIGN: Cross-sectional, population-based study dealing with
      diabetes prevalence in northern Spain. PATIENTS: Two hundred and fifty-seven
      apparently healthy Caucasian subjects consecutively enrolled in the study.
      MEASUREMENTS: Adiponectin serum levels were measured by enzyme-linked
      immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and
      insulin resistance by the homeostasis model of assessment (HOMA value). RESULTS:
      Adiponectin levels were negatively correlated with alanine aminotransferase (ALT)
      and gamma-glutamyltranspeptidase (GGT), before and after adjustment for sex, age,
      body mass index (BMI) and insulin resistance (ALT; r = -0.32, P < 0.001;
      adjusted: r = -0.13, P = 0.033; GGT; r = -0.31, P < 0.001; adjusted: r = -0.16, P
      = 0.011). Additionally, adiponectin correlated with alkaline phosphate (ALKP)
      only after adjusting for the same confounding variables (r =-0.10, P = 0.098;
      adjusted: r = -0.14, P = 0.031). A general linear model, adjusting for age, sex
      and BMI, was constructed to predict the decrease in circulating adiponectin for
      each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value
      above the median, serum adiponectin decreased by -0.97 mg/l (95% CI -1.46 to 
      0.48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin
      resistance, predicted serum concentrations of both ALT and GGT, explaining 19%
      and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or
      insulin resistance, explained 20% of ALKP variance. CONCLUSIONS: Adiponectin
      levels are associated in healthy humans with plasma concentrations of various
      liver function tests. The contributions of adiponectin to maintaining liver
      integrity through the regulation of both insulin sensitivity and/or the
      inflammatory response merit further studies.

PMID- 14725690
TI  - Evaluation of bone mineral density of the peripheral skeleton in pre- and
      postmenopausal women with newly diagnosed endogenous Cushing's syndrome.
AB  - OBJECTIVE: Cushing's syndrome (CS) is a well recognized cause of bone loss.
      Although many previous studies have shown decreased bone mineral density (BMD) in
      the lumbar spina and proximal femur of patients with endogenous CS, so far, the
      data estimating BMD in their peripheral skeleton are sparse. The aim of the
      present study was to evaluate BMD in the forearm and heel of women with newly
      diagnosed CS and to investigate its possible correlation with serum osteocalcin
      (BGP) and 24-hour urinary free cortisol levels (UFC). PATIENTS AND METHODS: BMD
      in the forearm (distal and ultradistal area) of 29 (13 premenopausal and 16
      postmenopausal) women with newly diagnosed CS (18 with pituitary adenoma, 10 with
      adrenal tumor and 1 with ectopic) was measured by dual x-ray absorptiometry
      (DEXA) and was compared with BMD of 29 age, body mass index (BMI)- and oestrogen
      status matched healthy controls. Furthermore, in 18 (9 premenopausal and 9
      postmenopausal) of the above patients (14 with pituitary adenoma, 5 with adrenal
      tumor and 1 with ectopic) broadband ultrasound attenuation (BUA) by quantitative
      ultrasound (QUS) of the heel was estimated and 18 age-, BMI- and oestrogen status
      matched healthy women served as controls. In all the patients serum BGP and UFC
      were measured at the time of diagnosis of CS. RESULTS: Compared to their matched
      controls, BMD in the forearm and BUA values in the heel did not differ in the
      premenopausal women with CS, while in the postmenopausal group BMD in the forearm
      was decreased (P < 0.05) but not BUA. Apart from a weak negative correlation
      between serum BGP and BMD in the ultradistal site of the forearm in premenopausal
      women (P = 0.05), serum BGP and UFC did not show significant correlation with BMD
      or BUA. CONCLUSIONS: BMD in the forearm is reduced only in postmenopausal women
      with newly diagnosed endogenous CS, while BUA in the heel is unaffected in both
      pre- and postmenopausal patients. Moreover, serum BGP and UFC do not seem to be
      relevant markers for assessing bone loss in the peripheral skeleton at the time
      of diagnosis of hypercortisolemia.

PMID- 14725691
TI  - Cushing's syndrome as a manifestation of hypothyroidism.

PMID- 14725692
TI  - The prevalence of diabetes mellitus in the parents of women with Turner's
      syndrome.

PMID- 14725693
TI  - Developing a CLEAR vision.

PMID- 14725694
TI  - Sentinel lymph node biopsy for thyroid cancer: why bother?

PMID- 14725695
TI  - Crossroads for surgery in Australia and New Zealand.

PMID- 14725696
TI  - Background and perioperative risk factors for prolonged hospital stay after
      resection of colorectal cancer.
AB  - BACKGROUND: The aim of this study was to identify independent background and
      perioperative risk factors for prolonged postoperative hospital stay among
      patients having a resection for colorectal cancer. METHODS: Data from 1095
      consecutive resections performed by specialist colorectal surgeons between 1995
      and 2001 were examined by multiple least squares regression. Each putative risk
      factor was coded 0 if absent and 1 if present and postoperative stay was measured
      in days, so that the unstandardized partial regression coefficients (B) represent
      days of additional stay if the factor was present. Confidence intervals are at
      the 95% level. RESULTS: Of 35 factors examined, the following 11 had a
      significant independent association with postoperative stay: urgent operation (B
      = 4.2, CI 2.2-6.2); preoperative stay>5 days (B = 4.2, CI 2.7-5.7); perioperative
      transfusion (B = 3.1, CI 2.2-4.2); adjacent organ or structure involved (B = 3.0,
      CI 1.2-4.9); stoma constructed (B = 2.6, CI 1.8-3.5); peripheral vascular disease
      (B = 2.3, CI 0.4-4.1); age > or =75 years (B = 2.2, CI 1.2-3.1); respiratory
      disease (B = 1.7, CI 0.5-2.8); American Society of Anesthetists' (ASA)
      classification>Class 2 (B = 1.5, CI 0.4-2.5); splenic flexure mobilized (B = 1.4,
      CI 0.5-2.3); private hospital (B = 1.4, CI 0.3-2.5). CONCLUSIONS: Together these
      factors accounted for only a fifth of the variability in length of stay and few,
      except possibly ASA, were susceptible of interventions that might reduce stay.
      Postoperative morbidity, which is largely unpredictable, remains the major cause
      of prolonged hospital stay.

PMID- 14725697
TI  - Sentinel lymph node dissection in papillary thyroid carcinoma.
AB  - BACKGROUND: Occult lymph node (LN) metastasis is common in papillary thyroid
      carcinoma. Sentinel lymph node (SLN) biopsy has been proven to be successful and
      accurate to predict the nodal status in melanoma and breast cancer. We
      investigate the use of SLN in papillary thyroid carcinoma. METHODS: Patients of
      previously untreated papillary thyroid carcinoma, diagnosed preoperatively by
      fine-needle cytology without any palpable cervical LN are prospectively studied.
      Blue dye injection was utilized for the SLN biopsy followed by central
      compartment lymphadenectomy. The histopathological results of the SLN and
      lymphadenectomy specimens were compared. RESULTS: Fifteen consecutive patients
      underwent surgery including SLN biopsy for papillary thyroid carcinoma. Occult
      nodal metastases were identified in 10 patients (67%). The other five cases had
      no nodal metastasis. SLN were found in 10 cases. One, two and three SLN were
      present in three, three and four patients, respectively. SLN were located in the
      central compartment in eight cases. The SLN were found in the lateral compartment
      in one case. In the remaining one case, the SLN were found in both the central
      and lateral compartments. Of the group with found SLN, false negative occurred in
      one case. The overall accuracy of the SLN in predicting the nodal status was 90%.
      The sensitivity, specificity, positive predictive value and negative predictive
      value were 88%, 100%, 100% and 67%, respectively. No complications were directly
      related to SLN biopsy. CONCLUSION: Occult nodal spread is frequently encountered
      in papillary thyroid carcinoma. SLN biopsy is safe and feasible in papillary
      thyroid cancer, however further studies are necessary to improve the diagnostic
      accuracy prior to routine clinical use.

PMID- 14725698
TI  - Suturing efficiency during hiatal repair for laparoscopic fundoplication.
AB  - BACKGROUND: An increasingly important part of general surgical training is the
      development of skills in advanced laparoscopic surgery. However, this aspect of
      laparoscopy is not always well taught, and there is scope for improving both
      training and the assessment of performance. Recently, the improved affordability
      and accessibility of digital video technology and supporting computer systems has
      enabled critical analysis of operative techniques in laparoscopic surgery to be
      carried out inexpensively. The aim of the present project was to develop a method
      for the objective analysis of a laparoscopic suturing task in the real clinical
      environment, so that surgeon-in-training performance could be objectively
      evaluated. METHODS: Eight videos of laparoscopic fundoplication procedures were
      used and the process of posterior hiatal repair was specifically analysed. The
      procedures were carried out by three operators, each with a different level of
      advanced laparoscopic experience. Two blinded assessors independently analysed
      the videos in 5-s intervals at two separate sittings. Analysis concentrated on
      the types of movements as well as their efficiency in progressing the task.
      RESULTS: The total time taken for the posterior hiatal repair varied between 165
      and 350 s (mean 240), and the mean number of actions was 42 (range 25-55). The
      mean percentage of efficiency (actions deemed 'very efficient' and 'efficient'vs
      actions deemed fair or inefficient) was 44% overall. More experienced surgeons
      took less time to complete the hiatal repair and had a higher percentage of
      efficiency of actions than inexperienced surgeons. Inefficient or unnecessary
      movements could be identified; these were less common for the more experienced
      surgeons. CONCLUSION: Video deconstruction enabled critical analysis of hiatal
      suturing in advanced laparoscopic surgery, highlighting inefficient actions. This
      offers a method for objectively assessing technique using readily available
      equipment. The method could be used to provide constructive feedback to surgical
      trainees.

PMID- 14725699
TI  - Damage control laparotomy in the Australian military.
AB  - Damage control laparotomy (DCL) is a physiological approach to the management of
      selected critically injured patients where the surgical technique is directed at
      minimising the metabolic insult, rather than restoring anatomic integrity. DCL
      consists of an abbreviated initial laparotomy that is limited to control of
      haemorrhage and contamination, intra-abdominal packing, and temporary closure.
      Secondary resuscitation continues in the intensive care unit for 24-48 h until
      normal physiology has been restored. The subsequent reoperation involves removal
      of the packing with definitive repair and closure. Using this approach 50% of
      civilian patients who would previously have died undergoing a definitive trauma
      laparotomy will survive. Doctrinal change in Australia has yet to enshrine a
      strong focus on restoration of key physiological variables as a major objective
      in treatment of all wartime casualties. Yet the philosophy of damage control is
      uniquely suited to the Australian military environment. However, transition of
      DCL to the military setting has to take account of operational constraints. The
      most important unresolved issue is how to provide adequate postoperative
      intensive care. An evacuation capability incorporating critical care transport
      teams needs to be present, as the patient must reach definitive care within 48 h.

PMID- 14725700
TI  - Anatomy of the pudendal nerve and its terminal branches: a cadaver study.
AB  - BACKGROUND: This study documents the anatomy of the pudendal nerve, which has a
      major role in maintaining faecal continence. Unexpected faecal incontinence can
      develop following perineal surgery even when the anal sphincters are not damaged.
      In addition, injury to the pudendal nerve might be encountered during pelvic
      procedures such as a sacrospinous colpopexy. METHODS: An anatomical study on 28
      cadavers was conducted to examine the course of the pudendal nerve and its
      branches in the perineum. RESULTS: In five of the 28 cadavers dissected (four
      male, one female), a nerve plexus was found within the ischiorectal fossa in
      close proximity to the anal sphincters. The plexus received contributions from
      interconnecting branches of the inferior rectal and perineal nerves to innervate
      the external anal sphincter. In 11 of the 28 cadavers (five female, six male) an
      additional nerve arose from the medial aspect of the pudendal nerve at the level
      of the sacrotuberous and sacrospinous ligaments. This nerve continued distally
      and gave several branches to the perineum and the levator ani muscle. CONCLUSION:
      A sound knowledge of the anatomical variations of the pudendal nerve and its
      branches is essential for all surgeons operating in the perineal region.

PMID- 14725701
TI  - Somatosensory evoked potentials predict neurolysis outcome in meralgia
      paraesthetica.
AB  - BACKGROUND: The role of somatosensory evoked potentials (SEP) in predicting the
      outcome of nerve entrapment syndrome following surgical release has not been
      fully verified. METHODS: All patients included in our study had preoperative SEP
      recordings and had undergone neurolysis for treatment of meralgia paraesthetica
      by our senior author (KNC) between 1996 and 2000. The outcome of surgery was
      assessed 6 weeks after the procedure; follow up was continued at 3 month
      intervals if symptoms persisted. Telephone interviews were conducted to assess
      long-term results. Univariate and multivariate logistic regression analyses were
      used to establish the predictive value of side-to-side N1 and P1 latency
      differences in obtaining complete relief of symptoms following surgery. RESULTS:
      Twenty-four patients who had preoperative SEP recordings and had undergone
      neurolysis for meralgia paraesthetica were followed for 4.0 +/- 1.5 (SD) years. A
      prolonged side-to-side N1 latency difference (DeltaN1) was found to be
      significantly associated with complete relief of symptoms at about 6 weeks
      postoperatively, after adjustment for age, sex and duration of symptoms (OR,
      1.75; CI, 1.03-2.96). Logistic regression identified a critical cut-off value of
      8 ms (OR, 27.2; CI, 1.4-547.0). This association disappeared with longer follow
      up. CONCLUSION: Somatosensory evoked potentials provide significant data for
      prediction of good surgical outcome for meralgia paraesthetica. Re-evaluation of
      the diagnosis, adequate trial of conservative treatments and special attention to
      anomalous branches are recommended for patients with low preoperative DeltaN1
      values.

PMID- 14725702
TI  - Determination of amputation level in ischaemic lower limbs.
AB  - BACKGROUND: A properly performed amputation can not only be lifesaving for the
      patient, but may often be a better therapeutic alternative than an ill-conceived,
      futile attempt at a vascular reconstruction doomed to fail for lack of adequate
      recipient vessels. Currently there are no consistent criteria that can be applied
      before surgery. The purpose of the present investigation was to find a reliable
      method of determining the best amputation level in an ischaemic lower extremity.
      METHODS: In the present study the author has tried to devise a 'score' for distal
      run-off vessel patency as shown by the preoperative angiogram to determine the
      most appropriate amputation level. The author has reviewed the level of
      amputation on ischaemic lower extremities in the vascular surgery unit of the
      Austin and Repatriation Medical Centre (ARMC) over the last 5 years. Two hundred
      and two patients have undergone 232 lower extremity amputations at ARMC. RESULTS:
      The author used chi2 corrected testing and found a good correlation between the
      score and the level of amputation. The lower the score, the higher the level of
      amputations (chi2 = 289.23, P < 0.005). The author could predict that with a
      score of <12 a patient would probably need an above-knee amputation; for a score
      from 12 to 19, a below-knee amputation; for a score of 20-25 a forefoot
      amputation would be sufficient and for a score of>25 a toe amputation would be
      all that was required. CONCLUSION: The use of a scoring system dependent on the
      preoperative angiogram to assess the run-off vessel situation provides a
      practicable and direct way to help predict the level of amputation in an
      ischaemic lower extremity. However, it is not totally reliable and should be used
      as one of the factors to be considered when an amputation is required.

PMID- 14725703
TI  - Deep venous valve reconstruction for non-healing leg ulcers: techniques and
      results.
AB  - BACKGROUND: The purpose of the present paper was to report clinical and imaging
      results of a 5 year experience of deep venous valve surgery with evaluation of
      end-points at 2 year follow up for the management of non-healing venous leg
      ulcers in 137 patients. METHODS: Between October 1994 and November 1999, 137
      patients (169 limbs) underwent deep vein reconstructions for non-healing venous
      leg ulcers of clinical, etiological, anatomical, pathological classification
      (CEAP) C6 class, as a 'last resort' treatment. End-points of the study were post
      valve reconstruction, freedom from leg ulceration, vein valve patency and
      competency at 2 years. Primary refluxive disease was present in 96 patients (118
      limbs). External valvuloplasty was performed in 12 limbs (19 valves) and internal
      valvuloplasty was performed in 90 limbs (144 valves). External supports were used
      in 16 limbs (16 valves). Multilevel (2-3) reconstructions were performed in 37
      limbs. Forty-one patients had secondary valvular defects involving 51 limbs.
      Axillary-femoral vein or saphenofemoral vein valve transplant was performed for
      29 patients (35 limbs) and three patients (three limbs), respectively,
      saphenofemoral venous transposition was performed in three patients (four limbs),
      and femoral/popliteal vein ligation was carried out in six patients (nine limbs).
      RESULTS: Two year results of external valvuloplasty showed ulcer healing in 50%
      of limbs with maintenance of competency at only 31% of valve stations. Internal
      valvuloplasty was the most durable valve repair procedure with 2 year leg ulcer
      healing rates of 67% and valve station competency of 79%. For secondary
      incompetence, valve transplants had a significant deterioration in valve patency
      and competence at 2 years: 58% and 47%, respectively, with 55.3% leg ulcer
      healing. It was also noted that single-level repairs or single valve transplants
      had lower ulcer healing rates than multilevel repairs or valve transplants with
      multiple valve stations. CONCLUSION: In a 2 year follow up, valvular
      reconstruction for refluxive disease is effective in healing venous ulcers that
      defy conservative management and superficial/perforator venous surgery.
      Furthermore, these procedures appear more promising for primary than for
      secondary incompetence. Multilevel or multivalve reconstructions yield superior
      results to single-level repairs in medium-term follow up.

PMID- 14725704
TI  - Is capitonnage unnecessary in the surgery of intact pulmonary hydatic cyst?
AB  - BACKGROUND: Hydatid disease, a parasitosis, is still an important health problem
      in Turkey. Surgery is the choice of treatment for pulmonary hydatid cyst. In this
      study, cystotomy and capitonnage were compared to cystotomy. METHODS: Fifty-nine
      patients with 70 pulmonary intact hydatid cysts were surgically treated between
      1993 and 1999. There were 11 females and 48 males (range 4-58 years). Cystotomy
      and closure of bronchial openings were performed in all patients. The patients
      were divided into two groups. In Group A (n = 32 patients, n = 38 cysts), the
      cavity was closed (capitonnage), and in Group B (n = 27 patients, n = 32 cysts)
      capitonnage was not performed. The patients treated by other surgical methods
      (pericystectomy, lobectomy, and others) were not included in this study. RESULTS:
      Prolonged air leak (> 5 days) was found in one patient in Group A, and in four
      patients in Group B. Atelectasis developed in one patient in Group A, and in
      three patients in Group B. Additionally, in Group B pseudocystic appearance
      occurred in two patients and empyema in one patient. The duration of
      hospitalization was 9.8 +/- 2.1 days for Group A, and 12.4 +/- 3.2 days for Group
      B. There was a significant difference between the groups for hospital time (p <
      0.01). There was no mortality in either group. CONCLUSION: This study shows that
      capitonnage is a procedure that should not be easily abandoned, despite the
      current contrary opinions, because of its low complication rate.

PMID- 14725705
TI  - Case for postoperative surveillance following colorectal cancer resection.
AB  - Over 4 years have elapsed since the first National Health and Medical Research
      Council (NHMRC) guidelines were published for the management of patients after
      potentially curative resection of colorectal cancer. New information has now been
      published indicating that more intensive follow up than was originally
      recommended might provide a survival benefit for patients. This new information
      should be considered when formulating new NHMRC guidelines. In particular, meta
      analyses of published individual trials have suggested a survival advantage that
      was not evident in the individual studies. There have been significant
      developments in chemotherapy with new individual agents and use of agents in
      combination that have proved far more effective than previous protocols. The
      therapeutic effect of these developments is the downstaging of some patients with
      metastatic disease, which was previously unresectable, to undergo resection.
      Furthermore, there is now some evidence that palliation of patients with advanced
      disease is more effective if commenced before the development of symptoms and
      this needs to be considered in the assessment of the benefits of follow up. There
      have been limited studies of cost-effectiveness, but international analyses
      suggest that the costs associated with more intensive follow-up regimes are
      within the accepted cost parameters associated with the management of many other
      conditions.

PMID- 14725706
TI  - Gene therapy in orthopaedic surgery: the current status.
AB  - The first successful gene therapy trial was reported in 1991. Since then,
      successful gene transfer in cultured cells and small animals has been reported by
      many studies, with achievement of at least transitory high levels of exogenous
      gene expression. Over 400 clinical protocols for gene therapy have been approved,
      involving over 4000 patients. However, publication of the results of these gene
      therapy trials has been limited, with only 80 published reports as of 2002. The
      majority of clinical gene therapy trials reported so far have been phase I or
      phase II trials, which are concerned mainly with safety issues and have focused
      on the treatment of malignancies and other potentially fatal conditions. The
      death of a patient in 1999 from systemic administration of an adenoviral vector
      and recent reports of leukaemia in two patients in a clinical gene therapy trial
      have led to a further re-evaluation of the safety of gene therapy and the role
      for gene therapy in clinical practice. This review outlines the current status of
      gene therapy as it relates to orthopaedic diseases and highlights the areas where
      progress is still to be made.

PMID- 14725707
TI  - Management of colorectal cancer patients in Australia: the National Colorectal
      Cancer Care Survey.
AB  - BACKGROUND: The National Colorectal Cancer Care Survey was undertaken to
      determine the management patterns for individuals newly diagnosed with colorectal
      cancer in Australia. METHODS: Between 1 February and 30 April 2000, all new cases
      of colorectal cancer registered at each Cancer Registry within Australia were
      entered into the survey. This generated a questionnaire that was sent to the
      treating surgeons. Chi-squared and logistic regression analyses were used to
      determine levels of statistical significance for the various comparisons of
      interest. RESULTS: Of 2383 surgical questionnaires generated, 2015 (85%) were
      completed. A total of 1911 patients (95% of those who responded to the
      questionnaire) had an operation. Of the 86 guidelines for the management of
      colorectal cancer published by the National Health and Medical Research Council,
      the survey allowed for comparison between 18 of these, which covered a spectrum
      of surgical management. Thromboembolic prophylaxis was given to 1843 patients
      (96.4%) undergoing surgery. Prophylactic antibiotics were commonly used, but
      there appear to be issues regarding the best regimen to use. Curative resections
      were carried out in 1563 patients (81.8%), with anterior resections being the
      most commonly performed procedure. Adjuvant therapy was regularly used, but not
      all eligible patients were offered such treatment. CONCLUSION: With the
      considerable resources required to develop clinical practice guidelines, studies
      like this are essential to monitor the impact of the guidelines. To ensure that
      the guidelines are in line with current evidence, regular reviews of the
      guideline recommendations are required.

PMID- 14725708
TI  - Aortic aneurysm repair with a functioning renal transplant: therapeutic options.
AB  - BACKGROUND: Aortic aneurysm repair in the presence of a functioning renal
      transplant carries significant risks of renal ischaemia. We describe the
      management of patients undergoing this treatment by using a temporary, externally
      sited axillofemoral bypass and discuss other treatment options. METHODS: Three
      patients underwent a temporary, externally sited axillary artery to common
      femoral artery bypass. The aneurysm was then dissected via a transperitoneal
      incision. When the aneurysm was clamped, the axillofemoral graft was opened
      allowing retrograde perfusion to the renal transplant. RESULTS: All three
      patients made a good recovery without postoperative deterioration of renal
      function. CONCLUSION: Numerous methods of protecting the transplanted kidney have
      been described, including expeditious surgery with no renal protection or some
      form of temporary shunt to perfuse the donor iliac artery. Temporary insertion of
      an axillofemoral bypass adds 45-60 min of extra operating time if two surgeons
      are present. However, this technique should completely avoid transplant ischaemia
      and is an excellent technique for dealing with abdominal aneurysms in patients
      with functioning transplants.

PMID- 14725709
TI  - Intracorporeal ribbon gauze in laparoscopic surgery.
AB  - Good haemostasis optimizes laparoscopic visibility and performance. The use of
      suction reduces pneumoperitoneum and collapses the operative space, and the
      resulting fall in intra-abdominal pressure can increase the rate of bleeding.
      Therefore, other methods of improving laparoscopic visibility need to be
      investigated. In the present report we describe the effectiveness of a 20-40-cm
      length of 3-inch ribbon dressing gauze when introduced into the peritoneal cavity
      via a 10-12 mm laparoscopic port. Current results indicate that intracorporeal
      ribbon gauze can be used successfully during laparoscopic procedures as a suction
      filter, to assist haemostasis, to facilitate dissection and to provide atraumatic
      organ retraction.

PMID- 14725710
TI  - Being CLEAR: evaluation of a module to teach critical appraisal to surgeons.
AB  - The CLEAR (critical literature evaluation and research) module was developed to
      meet an identified need in both trainees and Fellows for the basic tools to allow
      them to plan research projects and evaluate research papers. This paper describes
      briefly the way in which the module was developed and presents results of
      participant evaluation of the mature product, which indicate a high level of
      satisfaction.

PMID- 14725711
TI  - Herbert Moran Memorial Lecture. World War I: the genesis of craniomaxillofacial
      surgery?
AB  - Herbert Moran enlisted in the Royal Army Medical Corps early in World War I. His
      autobiography captures the impact of contemporary experience of wartime gunshot
      wounds, seen in vast numbers and with little understanding of the requirements of
      wartime surgery. Wounds of the face and brain were numerous, especially in trench
      fighting. In France, Germany, Britain and elsewhere, surgeons and dentists
      collaborated to repair mutilated faces and special centres were set up to
      facilitate this. The innovative New Zealand surgeon Harold Gillies developed his
      famous reconstructive techniques in the Queen's Hospital at Sidcup, with the help
      of dental surgeons, anaesthetists and medical artists. The treatment of brain
      wounds was controversial. Many surgeons, especially on the German side, advocated
      minimal primary operative surgery and delayed closure. Others advocated early
      exploration and immediate closure; among the first to do so was the Austro
      Hungarian otologist Robert Barany. In 1918, the pioneer American neurosurgeon
      Harvey Cushing published well-documented proof of the desirability of definitive
      operative management done as soon as possible. Few World War I surgeons developed
      their knowledge of plastic surgery, neurosurgery and oral surgery in post-war
      practice. An exception was Henry Newland, who went on to pioneer the development
      of these specialties in Australasia. After World War II, the French plastic
      surgeon Paul Tessier created the multidisciplinary subspecialty of
      craniomaxillofacial surgery, with the help of his neurosurgical colleague Gerard
      Guiot, and applied this approach to the correction of facial deformities. It has
      become evident that the new subspecialty requires appropriate training programs.

PMID- 14725712
TI  - Training surgeon scientists.

PMID- 14725713
TI  - Use of extracorporeal shockwave lithotripsy to treat a pancreatic duct calculus.

PMID- 14725714
TI  - Necrotizing fasciitis of the face and orbit following complications with a tooth
      abscess.

PMID- 14725715
TI  - Lipid phosphate phosphatases dimerise, but this interaction is not required for
      in vivo activity.
AB  - BACKGROUND: Lipid phosphate phosphatases (LPPs) are integral membrane proteins
      believed to dephosphorylate bioactive lipid messengers, so modifying or
      attenuating their activities. Wunen, a Drosophila LPP homologue, has been shown
      to play a pivotal role in primordial germ cell (PGC) migration and survival
      during embryogenesis. It has been hypothesised that LPPs may form oligomeric
      complexes, and may even function as hexamers. We were interested in exploring
      this possibility, to confirm whether LPPs can oligomerise, and if they do,
      whether oligomerisation is required for either in vitro or in vivo activity.
      RESULTS: We present evidence that Wunen dimerises, that these associations
      require the last thirty-five C-terminal amino-acids and depend upon the presence
      of an intact catalytic site. Expression of a truncated, monomeric form of Wunen
      in Drosophila embryos results in perturbation of germ cell migration and germ
      cell loss, as observed for full-length Wunen. We also observed that murine LPP-1
      and human LPP-3 can also form associations, but do not form interactions with
      Wunen or each other. Furthermore, Wunen does not form dimers with its closely
      related counterpart Wunen-2. Finally we discovered that addition of a trimeric
      myc tag to the C-terminus of Wunen does not prevent dimerisation or in vitro
      activity, but does prevent activity in vivo. CONCLUSION: LPPs do form complexes,
      but these do not seem to be specifically required for activity either in vitro or
      in vivo. Since neither dimerisation nor the C-terminus seem to be involved in
      substrate recognition, they may instead confer structural or functional stability
      through dimerisation. The results indicate that the associations we see are
      highly specific and occur only between monomers of the same protein.

PMID- 14725716
TI  - Moderate beer consumption does not change early or mature atherosclerosis in
      mice.
AB  - BACKGROUND: Although the consumption of wine in particular has been associated
      with a lower risk of atherothrombotic cardiovascular disease, systematic reviews
      differ as to the relative protective effect of beer, wine and spirits. Two
      previous studies showed that red wine reduces fatty streak formation (early
      atherosclerosis) but not mature atherosclerosis in apolipoprotein (apo) E
      deficient (apoE-/-) mice. AIM OF THE STUDY: To determine whether a moderate beer
      intake would affect early and mature atherosclerotic lesion formation using
      control C57BL/6 and apoE-/- mice, respectively, as models. METHODS: Control
      C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild
      beer, dark beer or ethanol-free beer. The level of beer was designed to
      approximate the alcohol intake currently believed to be beneficial in reducing
      human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks,
      and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice
      were euthanized and atherosclerotic lesions quantified. Plasma lipid
      concentrations were also measured. RESULTS: The amount of atherosclerosis and
      average number of lesions in the proximal aortic region did not differ among
      groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively) and apoE-/-
      mice (p = 0.19 and p = 0.59, respectively). No consistent differences were
      observed in plasma lipid and lipoprotein concentrations among water, ethanol and
      beer groups. CONCLUSIONS: Moderate beer consumption does not change the
      development of early or mature atherosclerosis in mice. Our findings do not
      support the hypothesis of an anti-atherogenic effect of beer. Other potential
      protective actions of moderate beer consumption such as plaque stabilization, a
      reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic
      propensity to thrombosis, remain to be studied.

PMID- 14725717
TI  - Development and validation of a new global well-being outcomes rating scale for
      integrative medicine research.
AB  - BACKGROUND: Researchers are finding limitations of currently available disease
      focused questionnaire tools for outcome studies in complementary and alternative
      medicine/integrative medicine (CAM/IM). METHODS: Three substudies investigated
      the new one-item visual analogue Arizona Integrative Outcomes Scale (AIOS), which
      assesses self-rated global sense of spiritual, social, mental, emotional, and
      physical well-being over the past 24 hours and the past month. The first study
      tested the scale's ability to discriminate unhealthy individuals (n = 50) from
      healthy individuals (n = 50) in a rehabilitation outpatient clinic sample. The
      second study examined the concurrent validity of the AIOS by comparing ratings of
      global well-being to degree of psychological distress as measured by the Brief
      Symptom Inventory (BSI) in undergraduate college students (N = 458). The third
      study evaluated the relationships between the AIOS and positively- and negatively
      valenced tools (Positive and Negative Affect Scale and the Positive States of
      Mind Scale) in a different sample of undergraduate students (N = 62). RESULTS:
      Substudy (i) Rehabilitation patients scored significantly lower than the healthy
      controls on both forms of the AIOS and a current global health rating. The AIOS
      24-hours correlated moderately and significantly with global health (patients r =
      0.50; controls r = 0.45). AIOS 1-month correlations with global health were
      stronger within the controls (patients r = 0.36; controls r = 0.50). Controls (r
      = 0.64) had a higher correlation between the AIOS 24-hour and 1-month forms than
      did the patients (r = 0.33), which is consistent with the presumptive improvement
      in the patients' condition over the previous 30 days in rehabilitation. Substudy
      (ii) In undergraduate students, AIOS scores were inversely related to distress
      ratings, as measured by the global severity index on the BSI (rAIOS24h = -0.42,
      rAIOS1month = -0.40). Substudy (iii) AIOS scores were significantly correlated
      with positive affect (rAIOS24h = 0.56, rAIOS1month = 0.57) and positive states of
      mind (rAIOS24h = 0.42, rAIOS1month = 0.45), and inversely correlated with
      negative affect (rAIOS24h = -0.41, rAIOS1month = -0.59). CONCLUSIONS: The AIOS is
      able to distinguish relatively sicker from relatively healthier individuals; and
      correlates in expected directions with a measure of distress and indicators of
      positive and negative affect and positive states of mind. The AIOS offers a tool
      for CAM/IM research that extends beyond a disease emphasis.

PMID- 14725720
TI  - Local anesthetic resistance in a pregnant patient with lumbosacral plexopathy.
AB  - BACKGROUND: We report a case of a patient with apparent resistance to local
      anesthetics. While similar cases of failure of regional anesthetics are often
      attributed to technical failure, the overall clinical presentation and history of
      this patient suggests a true resistance to local anesthetics. CASE PRESENTATION:
      This patient presented for elective cesarean section and the decision for
      regional anesthesia was made. While attempting to place an epidural, the patient
      failed to achieve adequate skin analgesia despite multiple attempts at local
      infiltration. When a spinal was ultimately placed, sensory or motor blockade was
      not obtained despite no evidence of technical problems with technique. Further
      questioning revealed multiple prior episodes of local anesthetic failure in this
      patient. CONCLUSIONS: While the failure rate of spinal anesthesia has been shown
      range from 4-13% and is often attributed to technical failure, elements of this
      particular case suggest a true resistance to local anesthetics.

PMID- 14725718
TI  - Iron: a target for the management of Kaposi's sarcoma?
AB  - BACKGROUND: Kaposi's sarcoma (KS) is a mesenchymal tumour associated with human
      herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection
      is far higher than the prevalence of KS, suggesting that viral infection per se
      is not sufficient for the development of malignancy and that one or more
      additional cofactors are required. DISCUSSION: Epidemiological data suggest that
      iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a
      well-known carcinogen and may favour KS growth through several pathways. Based on
      the apoptotic and antiproliferative effect of iron chelation on KS cells, it is
      suggested that iron withdrawal strategies could be developed for the management
      of KS. Studies using potent iron chelators in suitable KS animal models are
      critical to evaluate whether iron deprivation may be a useful anti-KS strategy.
      SUMMARY: It is suggested that iron may be one of non-viral co-factors involved of
      KS pathogenesis and that iron withdrawal strategies might interfere with tumour
      growth in patients with KS.

PMID- 14725719
TI  - Peak plasma interleukin-6 and other peripheral markers of inflammation in the
      first week of ischaemic stroke correlate with brain infarct volume, stroke
      severity and long-term outcome.
AB  - BACKGROUND: Cerebral ischaemia initiates an inflammatory response in the brain
      and periphery. We assessed the relationship between peak values of plasma
      interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of
      stroke severity and outcome. METHODS: Thirty-seven patients with ischaemic stroke
      were prospectively recruited. Plasma IL-6, and other markers of peripheral
      inflammation, were measured at pre-determined timepoints in the first week after
      stroke onset. Primary analyses were the association between peak plasma IL-6
      concentration with both modified Rankin score (mRS) at 3 months and computed
      tomography (CT) brain infarct volume. RESULTS: Peak plasma IL-6 concentration
      correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and
      mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12
      months or stroke severity. Strong associations were also noted between either
      peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC)
      count, and all outcome measures. CONCLUSIONS: These data provide evidence that
      the magnitude of the peripheral inflammatory response is related to the severity
      of acute ischaemic stroke, and clinical outcome.

PMID- 14725721
TI  - Age- and region-dependent alterations in the GABAergic innervation in the brain
      of rats treated with amphetamine.
AB  - Mechanisms underlying the pathogenesis of psychotic disorders were explored by
      monitoring the expression of GABAergic neurons in an animal model. Male rats of
      postnatal days 21 and 60 were intraperitoneally injected with amphetamine (Amph),
      5 mgkg, or saline three times daily for 6 d. After 1-d or 14-d withdrawal from
      Amph, they were challenged on day 8 (W1d) or on day 21 (W14d) with a single same
      dosage and then perfused. Immunostaining on the brain sections using an anti
      glutamic acid decarboxylase (GAD67) antiserum revealed that the Amph treatment
      increased the densities of the GAD67-immunoreactive boutons by approx. 36 to 79%
      above controls in the layers of motor and somatosensory cortices of the W1d
      juvenile, whereas for those of W14d, the densities resembled controls. For the
      Amph-treated adults of both W1d and W14d, the GAD67 immunoreactivity increased 56
      133% in these layers. In the striatum, the GAD67 densities responded to Amph in a
      similar manner to the neocortices. However, for the nucleus accumbens, the GAD67
      terminals were up-regulated by 22-64% in all Amph-injected rats of both ages. In
      the hippocampal CA1CA3 region of the Amph-administered juvenile, increases of 24
      27% of GAD67 terminals occurred for W1d and W14d animals. By contrast, however,
      in the W1d Amph-injected adult, there were increases of 42-48% in CA1-CA3, at
      W14d the GAD67 boutons resembled controls or were reduced. An age-dependent
      correlation was implicated between behavioural and immunostaining observations.
      The data support the view that inhibitory regulation is involved in neuronal
      responses to chronic psychostimulant administration and reflect differential
      neuronal plasticity among the developing and adult brain regions.

PMID- 14725722
TI  - Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone
      (DHEA) and DHEA-sulphate (DHEA-S) levels.
AB  - Lithium (Li) is an established effective treatment for bipolar disorder. However,
      the molecular mechanism of its action is still unknown. Dehydroepiandrosterone
      (DHEA) and its sulphate ester (DHEA-S) are adrenal hormones also synthesized de
      novo in the brain as neurosteroids. Recent studies have suggested that DHEA has
      mood-elevating properties and may demonstrate antidepressant effects. 3(2)
      Phosphoadenosine 5-phosphate (PAP) phosphatase is a novel Li-inhibitable enzyme
      involved in sulphation processes. In the present study we examined the impact of
      10 d Li treatment on serum and brain DHEA and DHEA-S levels in rats. Our results
      show that Li administration lowered frontal cortex and hippocampus DHEA and DHEA
      S levels, in line with our hypothesis assuming that Lis inhibition of PAP
      phosphatase leads to elevated PAP levels resulting in inhibition of sulphation
      and reduction in brain DHEA-S levels. Future studies should address the
      involvement of neurosteroids in the mechanism of Lis mood stabilization.

PMID- 14725723
TI  - Irinotecan in small-cell lung cancer: current data.
AB  - Irinotecan, a new topoisomerase I inhibitor, has significant activity in the
      treatment of untreated and previously treated patients with small-cell lung
      cancer (SCLC). In combination with cisplatin, a Japanese randomized trial showed
      a statistically significant survival advantage over cisplatin/etoposide in
      chemotherapy- naive patients with extensive-stage disease. This represents the
      first major advance in the treatment of extensive-stage SCLC in 20 years.
      Randomized trials in the United States are underway to confirm these impressive
      results. Meanwhile, trials incorporating irinotecan and cisplatin into treatment
      regimens for limited-stage disease are being conducted. Furthermore, irinotecan
      containing regimens with other agents such as carboplatin, etoposide, and
      paclitaxel in first- or second-line therapies for SCLC are being evaluated.
      Preliminary results are encouraging. This article will highlight the exciting
      results achieved with irinotecan in SCLC and discuss its promising future in this
      disease.

PMID- 14725724
TI  - Irinotecan: future directions in small-cell lung cancer.
AB  - Small-cell lung cancer (SCLC) accounts for approximately 20%-25% of all cases of
      lung cancer and has an especially poor prognosis, resulting in about 25% of all
      lung cancer deaths. About two thirds of patients with SCLC will present with more
      advanced and less treatment-sensitive extensive disease (ED). Five-year survival
      is negligible for patients with ED. Combination chemotherapy is the most
      effective treatment modality for SCLC. For patients with ED SCLC, chemotherapy
      can increase median survival from about 1.5 months to 7-11 months, with 2-year
      survival uncommon. Several new agents, including carboplatin, ifosfamide, and the
      taxanes, have been shown to be active against SCLC but have not resulted in
      improvement in overall survival. Among the most active to date has been the
      topoisomerase I inhibitor, irinotecan. A recent phase III study of the
      combination of irinotecan/cisplatin indicates improved survival over cisplatin/
      etoposide. Survival results indicate that overall survival with
      irinotecan/cisplatin was significantly better than the standard treatment arm
      (12.8 months vs. 9.4 months, P = 0.0021, unadjusted one-sided log-rank test).
      These results represent a major advance and, if confirmed, may establish this
      regimen as the new standard of care for ED SCLC. These future directions will
      include the confirmation of the Japanese phase III trial in ED SCLC, evaluating
      the role of irinotecan in limited-stage disease, new doublet and triplet
      combinations containing irinotecan, and evaluation of irinotecan combinations
      with the newer molecularly targeted agents (ie, SU5416).

PMID- 14725725
TI  - Irinotecan and platinums in the treatment of non small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer death in the United States and in the
      world. In the United States, lung cancer ranks first in cancer deaths for both
      men and women. The 5-year survival rate is only 15%, but this has improved
      considerably from the 5% rate in the early 1960s. For many years, the standard
      therapy for patients with advanced, stage IIIB and IV non small-cell lung cancer
      (NSCLC) was best supportive care, which consisted of palliative radiotherapy,
      pain management, and other symptom management. The median survival for these
      patients was only 4 months, and more than 85% died in the first year after
      diagnosis. Cisplatin was the first drug that was shown to prolong the survival of
      patients with advanced lung cancer. Meta-analyses of randomized trials showed
      that cisplatin reduced the hazard rate of death by 26%, increased median survival
      from 4 to 6 months, and increased 1-year survival from 15% to 25%. Cisplatin
      based therapy also relieved symptoms in the majority of patients and improved the
      quality of life as assessed by patients themselves. Still, further advances are
      desperately needed, as three fourths of the cisplatin-treated patients die within
      a year of diagnosis. Topoisomerase I inhibitors are a new class of
      chemotherapeutic agents introduced into lung cancer therapy during the 1990s.
      Irinotecan (CPT-11) was shown to be active in patients with both small-cell and
      non small-cell lung cancers. The activity of irinotecan in advanced NSCLC made it
      logical to combine irinotecan with the two platinums, cisplatin and carboplatin.
      The combination of irinotecan with cisplatin produced response rates of about 40%
      in phase II trials conducted in previously un-treated patients with advanced
      NSCLC. The median survival in these studies ranged from 6-8 months, and the 1
      year survival rates ranged from 40%-60%. Because carboplatin is more convenient
      and better tolerated than cisplatin, a number of more recent phase II trials have
      evaluated the combination of irinotecan and carboplatin in patients with advanced
      NSCLC. These trials produced results similar to those achieved with
      irinotecan/cisplatin and with other two-drug combinations such as
      paclitaxel/carboplatin and gemcitabine/ cisplatin. The excellent activity of the
      two-drug combination or irinotecan and a platinum led to trials of three-drug
      combinations, such as irinotecan/carboplatin/paclitaxel. Preliminary results from
      these studies showed excellent survival, although the toxicity required some
      dosage reductions. Randomized trials will be necessary to determine whether such
      three-drug combinations will be preferred over standard two-drug combinations.

PMID- 14725726
TI  - Irinotecan and taxane combinations for non small-cell lung cancer.
AB  - Based on nonoverlapping toxicity profiles and at least additive cytotoxicity in
      preclinical models, chemo-therapy regimens have been developed that feature the
      combination of irinotecan and a taxane drug. In the first study, the optimal
      doses of paclitaxel and irinotecan were 75 mg/m2 and 50 mg/m2, respectively, when
      chemotherapy was administered weekly for 4 consecutive weeks, followed by a 2
      week rest. The dose-limit-ing toxicity for this regimen was neutropenia, and the
      most prominent nonhematologic toxicities were mild diarrhea and fatigue.
      Pharmacokinetic studies failed to demonstrate any sequence-dependent interaction
      be-tween these agents on the metabolism of irinotecan or its major metabolite.
      This regimen has been modified, with chemotherapy given on day 1 and day 8 every
      3 weeks, and is being tested further in previously un-treated advanced non small
      cell lung cancer (NSCLC). In a second trial, irinotecan was combined with
      docetaxel on a weekly schedule. When chemotherapy was given weekly for 4 weeks,
      followed by a 2-week rest, the recommended doses of docetaxel and irinotecan were
      35 mg/m2 and 50 mg/m2, respectively. Low-grade gastrointestinal toxicity and
      asthenia were the dose-limiting toxicities. The treatment schedule was modified,
      with chemotherapy given on days 1 and 8 of a 21-day cycle, and patients are
      currently being treated with docetaxel 35 mg/m2 and irinotecan 65 mg/m2. Among
      the 10 evaluable patients with NSCLC in this second study, there was one partial
      response lasting 24 weeks and four patients with stable disease, including one
      patient who had progressive disease on a prior paclitaxel-containing regimen. The
      combinations of irinotecan and a taxane on a weekly schedule are active and well
      tolerated and deserve further evaluation in the treatment of NSCLC.

PMID- 14725727
TI  - Irinotecan (CPT-11) in triplet combinations in patients with advanced non small
      cell lung cancer: a review and report of a phase I/II trial.
AB  - The objectives of this phase I/II trial were to determine the maximum tolerated
      dose, toxicities, and the dose suitable for phase II/III trials of irinotecan
      (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non
      small-cell lung cancer (NSCLC). Seventy-three patients with stage IIIB/IV NSCLC
      were enrolled in this multicenter, phase I/II study. The initial regimen was
      paclitaxel 225 mg/m2 over 3 hours, followed by carboplatin at an area under the
      curve (AUC) of 6 over 30 minutes on day 1 and CPT-11 starting at 40 mg/m2 over 90
      minutes on days 1 and 8, every 3 weeks. Dose-limiting toxicity occurred in three
      of the original seven patients. The regimen was amended with doses reduced to
      paclitaxel 175 mg/m2 over 3 hours, carboplatin AUC = 5, and CPT-11 at 40 mg/m2,
      all on day 1 every 3 weeks. Dose escalation of CPT-11 proceeded to 80 mg/m2 and
      125 mg/m2 before dose-limiting toxicities were experienced. Subsequent patients
      received an intermediate CPT-11 dose of 100 mg/m2. Doses suitable for phase II
      study were determined to be paclitaxel 175 mg/m2 over 3 hours, carboplatin AUC =
      5, and CPT-11 100 mg/m2. The pri-mary first-cycle dose-limiting toxicities were
      neutropenia and diarrhea. The most common grade 3/4 toxicity observed during all
      cycles was neutropenia. On the phase I portion of the study, objective tumor
      response was observed in 39% (12 of 31, 95% confidence interval: 22%-58%). The
      median time to tumor progression was 6.8 months, median survival was 11.0 months,
      and 1-year survival probability was 0.46. These data were confirmed in the phase
      II portion with a 30% objective response rate, median time to progression of 5.6
      months, median survival of 12.5 months, and a 1-year survival probability of
      0.50. In conclusion, CPT-11 100 mg/m2, paclitaxel 175 mg/m2, and carboplatin AUC
      = 5 given every 3 weeks can be safely administered in patients with advanced
      NSCLC. Neutropenia and diarrhea are the dose-limiting toxicities. The combination
      shows appreciable activity, and survival data are favorable, warranting further
      study of this regimen. A review of other irinotecan-containing triplet
      combinations is presented.

PMID- 14725728
TI  - Topoisomerase I inhibitors in the combined modality therapy of lung cancer.
AB  - Locally advanced non small-cell lung cancer (NSCLC) represents 30%-40% of all
      pulmonary malignancies. Despite the fact that the disease is confined to the
      chest, most patients will eventually succumb to their dis-ease. Therefore, the
      management of NSCLC is undergoing rapid evolution with hope of improving overall
      survival. The arrival of a new generation of chemotherapeutic agents, including
      the taxanes, gemcitabine, and topoisomerase inhibitors such as irinotecan and
      topotecan, offers the hope of real advances against this malignancy. Irinotecan
      and topotecan are camptothecin derivatives that are felt to exert their cytotoxic
      effects by targeting topoisomerase I. It is believed that topoisomerase I
      inhibitors stabilize a DNA-topoisomerase I cleavable complex, and interactions
      between this complex and the replication machinery may lead to cell death. There
      is a significant volume of in vitro and in vivo data demonstrating that these
      topoisomerase I inhibitors also act as radiosensitizers. Early clinical data with
      topotecan suggests that it is a more active agent in small-cell lung cancer than
      it is in NSCLC despite a common mechanism of action with irinotecan. With the
      increasing data that exist on the improved outcome with concurrent chemoradiation
      treatment for malignancies including lung cancer and head and neck cancers, there
      is an impetus to pursue the addition of other drugs that can radiosensitize
      tumors and further improve local control. Irinotecan is undergoing early clinical
      trials in the combined modality setting in several different disease sites. This
      paper will review the in vitro and in vivo data on the ability of irinotecan and
      topotecan to render tumors more susceptible to ionizing radiation. It will then
      focus on the experience with both drugs and thoracic radiation in the treatment
      of NSCLC, in which irinotecan has yielded acceptable toxicity results and
      response rates in excess of 60% in early trials. It is hoped that newer treatment
      strategies, such as the combination of radiation and topoisomerase I inhibitors
      in lung cancer, will have a significant impact on cure rates in the future.

PMID- 14725729
TI  - Chemotherapy regimens in advanced non small-cell lung cancer: recent randomized
      trials.
AB  - The four chemotherapy regimens evaluated in Eastern Cooperative Oncology Group
      study 1594 (paclitaxel/ cisplatin, gemcitabine/cisplatin, docetaxel/cisplatin,
      and paclitaxel/carboplatin) are effective treatment options for the therapy of
      advanced non small-cell lung cancer (NSCLC). Only numerical differences have been
      noted in overall survival with these regimens, probably due to the fact that
      total therapy received by these patients was the same. There was an improved
      median time to progression with the gemcitabine/ cisplatin doublet. Choice of a
      chemotherapy regimen in practice is being based on the tolerability and side
      effect profile of these doublets. In the foreseeable future, we will see the use
      of selective and individualized therapy in addition to chemotherapy in the
      management of advanced NSCLC.

PMID- 14725730
TI  - Gemcitabine and carboplatin in advanced non small-cell lung cancer: a review.
AB  - Both gemcitabine and carboplatin have demonstrated activity in advanced non small
      cell lung cancer. The combination of gemcitabine and cisplatin has demonstrated
      equivalent or superior efficacy to other commonly used agents and two-drug
      combinations, and a recent Eastern Cooperative Oncology Group trial suggested
      that this regimen may have a slight advantage over other regimens in time to
      progression. The substitution of carboplatin for cisplatin offers the opportunity
      for a more well-tolerated regimen, and the combination of gemcitabine with
      carboplatin has now been studied in various clinical phase I and II trials. The
      administration of gemcitabine on a day-1-and-8 regimen with carboplatin appears
      to have a more favorable toxicity profile, especially with regard to platelet
      toxicity. Therefore, a number of ongoing trials, both phase II and phase III, are
      investigating the activity of this combination in locally advanced and metastatic
      non small-cell lung cancer. These trials will help define the role of this active
      and well-tolerated new regimen and, ultimately, its ability to be incorporated
      into multimodality therapy as well as with the new biologic agents for the
      treatment of non small-cell lung cancer.

PMID- 14725731
TI  - Gemcitabine and taxane combinations in non small-cell lung cancer.
AB  - Gemcitabine, docetaxel, and paclitaxel are among the most active agents available
      for the treatment of non small-cell lung cancer (NSCLC). Each has been shown to
      produce objective responses in approximately 20%-25% of previously untreated
      patients with advanced or metastatic NSCLC and to improve survival and quality of
      life when compared to best supportive care. In randomized clinical trials, these
      drugs have produced response rates and survival outcomes equal to older platinum
      based regimens and, when combined with a platinum compound, have produced the
      best results achieved to date in this disease. Because of their effectiveness and
      moderate toxicity profiles, investigators have studied novel combinations of
      these new agents. Multiple phase II clinical trials have explored a variety of
      doses and schedules of gemcitabine combined with docetaxel or paclitaxel.
      Randomized clinical trials have shown that gemcitabine 1000-1100 mg/m2
      administered on days 1 and 8 every 3 weeks combined with either docetaxel 100
      mg/m2 on day 8 or paclitaxel 200 mg/m2 on day 1 can produce response rates and
      survival outcomes at least equivalent to the newer platinum-based taxane
      regimens. More recently, several investigators have explored weekly
      administration of either docetaxel or paclitaxel with gemcitabine. Preliminary
      results are encouraging and suggest that these novel gemcitabine/taxane regimens
      could provide an alternative to standard platinum-based regimens.

PMID- 14725732
TI  - Combinations of three chemotherapeutic agents and two chemotherapeutic agents
      plus a targeted biologic agent in the treatment of advanced non small-cell lung
      cancer.
AB  - Lung cancer is the most common cause of cancer death in the world. In the United
      States, more than 28% of all cancer deaths are from lung cancer. In the past
      decade, a number of new drugs were introduced into the treatment of lung cancer
      including taxanes, gemcitabine, vinorelbine, and irinotecan. Combinations of one
      of these drugs with cisplatin, with carboplatin, or with one another were shown
      to be superior to best supportive care, to single-agent cisplatin, and in some
      instances, to a podophyllotoxin and cisplatin. Comparisons of the various two
      drug combinations showed that they are equivalent in efficacy although there are
      differences in convenience, cost, and toxicity. Many of these two-drug
      combinations are less toxic than older combinations, which allowed for the
      development of three-drug combinations that could be given in full dose and with
      acceptable toxicity. Phase II trials of several three-drug combinations including
      carboplatin/paclitaxel/gemcitabine and cisplatin/vinorelbine/gemcitabine showed
      response rates and survival rates that were somewhat higher than anticipated with
      a two-drug combination. These data led to three randomized trials of a doublet
      combination versus a triplet combination. Each of these trials showed a higher
      response rate and higher toxicity rates with the triplet combination. The
      toxicity rates were still acceptable with the triplet combinations. The survival
      was also superior in the triplet arms of each of the randomized trials.
      Unfortunately, the sample size in each of these studies was small and the
      survival differences are not statistically significant. Therefore, additional
      larger randomized trials are sorely needed. During the past decade, new
      molecularly targeted agents were introduced into the treatment of lung cancer and
      completed phase I and II trials. Objective responses were noted with many of
      these new agents. Several combinations of doublet chemotherapy with a new
      targeted agent have completed phase II trials with encouraging results. Some of
      these new triplets are now in phase III randomized trials.

PMID- 14725733
TI  - Future randomized trials for non small-cell lung cancer.
AB  - Combination chemotherapy is the standard of care for management of previously
      untreated, good performance status patients with advanced non small-cell lung
      cancer. Most of the regimens in use worldwide are platinum-based doublets. Recent
      data from the Eastern Cooperative Oncology Group suggest that multiple different
      platinum-based regimens produce similar response rates and overall survival when
      used as first-line treatment. In upcoming randomized trials designed to explore
      possible improvements in therapy, three different strategies are being evaluated.
      One involves head-to-head comparisons of new, often non-platinum-based doublet
      combinations with standard platinum-based, two-drug regimens. A second emphasizes
      the possible benefits of combinations using three cytotoxic agents compared to a
      two-drug standard. The third is focused on adding a new molecular targeting
      agent, such as an anti growth factor, growth factor receptor antibody, or an
      intracellular signal transduction inhibitor, to a standard combination of two
      cytotoxic drugs. This paper reviews some of the randomized phase III trials
      exemplifying each of these approaches to therapy for patients with advanced non
      small-cell lung cancer.

PMID- 14725734
TI  - Gemcitabine plus radiation therapy in the treatment of locally advanced non small
      cell lung cancer.
AB  - For stage III non small-cell lung cancer, there is a need for better systemic, as
      well as locoregional, control of the tumor. In an attempt to enhance this
      locoregional control, systemic chemotherapy has been given currently with
      radiation therapy. Gemcitabine, a novel deoxycytidine analogue, has been shown to
      be a potent radiosensitizer. This review focuses on the studies using gemcitabine
      concurrently with radiation therapy in the treatment of locally advanced non
      small-cell lung cancer.

PMID- 14725735
TI  - Single-agent docetaxel (Taxotere) in the treatment of advanced non small-cell
      lung cancer: clinical concepts and commentary.
AB  - Chemotherapy in recurrent or metastatic non small-cell lung cancer (NSCLC) has
      been shown to im-prove quality of life, and to provide a modest prolongation of
      survival. Docetaxel is a semisynthetic taxane that is an active agent for the
      treatment of NSCLC, both in previously untreated patients as well as those who
      have relapsed or progressed following cisplatin-based chemotherapy. After
      encouraging results in phase II studies, randomized trials have shown that
      treatment with single-agent docetaxel is superior to best supportive care for
      advanced NSCLC in both untreated and previously treated patients. This article
      will review the published data on the use of single-agent docetaxel in the
      treatment of advanced NSCLC.

PMID- 14725736
TI  - Docetaxel in combination with platinum compounds for non small-cell lung cancer.
AB  - Assessing the combination of docetaxel with cisplatin or carboplatin was based on
      their activity as single agents, their nonoverlapping toxicity profiles, and
      their lack of cross-resistance. Phase I studies of docetaxel in combination with
      cisplatin established that 75 mg/m2 of each agent could be administered with
      reasonable safety and appeared to be active in non small-cell lung cancer
      (NSCLC). We evaluated the docetaxel/cisplatin combination in patients with
      advanced NSCLC. The response rate was 32%, and the median survival was 11.5
      months. Efficacy was comparable to that observed in the Australian and French
      trials with the same combination. This is now being evaluated further in two
      large randomized trials for patients with advanced NSCLC and has been
      incorporated into the combined modality programs for early-stage disease.
      Carboplatin, devoid of the nephrotoxicity and neurotoxicity associated with the
      parent cis-platin, was then combined with docetaxel. The recommended dose of
      docetaxel for further evaluation in combination with carboplatin (AUC=6
      mg/mL.min) was 90 mg/m2 with filgrastim support and 80 mg/m2 without filgrastim
      support. Our phase II trial of the combination of docetaxel and carboplatin in
      advanced NSCLC demonstrated an overall response rate of 36%; median survival was
      13.9 months, and 1-year survival was 52%. Comparable activity has been seen by
      other investigators, and the regimen is being evaluated in two randomized trials.
      The combination of docetaxel with either of the two platinum agents has
      reasonable activity in NSCLC, though the carboplatin/docetaxel doublet appears to
      have a better therapeutic index.

PMID- 14725737
TI  - Docetaxel and gemcitabine: a nonplatinum combination for non small-cell lung
      cancer.
AB  - The 1990s have introduced a number of novel chemotherapeutic agents with activity
      in non small-cell lung carcinoma. Docetaxel and gemcitabine appear to be two of
      the most active new agents. Their use in non small-cell lung carcinoma has been
      associated with improvements in survival, palliation of symptoms, and maintenance
      of quality of life when compared to best supportive care. Options for treatment
      of non small-cell lung carcinoma after platinum have been limited. These newer
      agents have substantial activity in this subset of patients. This review focuses
      on the current data using the combination of docetaxel and gemcitabine in the
      fight against non small-cell lung carcinoma.

PMID- 14725738
TI  - Docetaxel and gemcitabine combinations in chemotherapy-pretreated non small-cell
      lung cancer.
AB  - Both docetaxel and gemcitabine are active against chemotherapy-pretreated non
      small-cell lung cancer (NSCLC). We previously demonstrated that weekly
      gemcitabine can be safely combined with monthly docetaxel with promising
      antineoplastic activity. In a recently completed phase II trial, 38 NSCLC
      patients failing upfront chemotherapy were treated with gemcitabine 800 mg/m2 on
      days 1, 8, and 15 and docetaxel 100 mg/m2 on day 1 every 4 weeks. The intent-to
      treat response rate was 33% (95% CI: 19%-55%), with one complete and 11 confirmed
      partial responses. Responses were seen at all disease sites and in 31% of
      patients refractory to front-line chemotherapy. The median time to disease
      progression for the responders was 8 months, and two have remained progression
      free for longer than a year. Hematological toxicities included grade 4
      neutropenia in half of patients, febrile neutropenia in 10%, and grade 3-4
      thrombocytopenia in 25%. The most prominent nonhematological toxicity was
      asthenia. We conclude that this doublet is active and safe, producing durable
      responses at all disease sites and in patients with platinum-refractory NSCLC.

PMID- 14725739
TI  - Trials of vinorelbine and docetaxel in the treatment of advanced non small-cell
      lung cancer.
AB  - Docetaxel was chosen for study in the combination chemotherapy of advanced non
      small-cell lung cancer on the basis of its reproducible high single-agent
      activity, novel mechanism of action, and relative lack of neurotoxicity.
      Preclinical and clinical data suggested schedule-dependent synergism with
      vinorelbine. Trials of docetaxel and vinorelbine have explored a variety of
      schedules. One approach has been to give docetaxel on day 1 of a 3-week cycle
      with vinorelbine on day 0 or days 1 and 5. Febrile neutropenia and non
      neutropenic infections have been dose limiting, and low-dose intensity (8-13
      mg/m2/week) of vinorelbine has been achieved. Our phase I study showed that
      docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 every 2 weeks could be safely given
      with prophylactic filgrastim. In the ensuing phase II trial, we observed a 51%
      confirmed response rate in 35 patients (95% confidence interval [CI]: 34-68).
      With a median follow-up of 12 months, the predicted median and 1-year survivals
      are 14 months and 60%, respectively. Use of prophylactic filgrastim and the every
      2-week schedule of administration allowed for single-agent dose intensity of both
      drugs to be given. Febrile neutropenia occurred in five patients and 5/384
      cycles. Cumulative toxicities of excessive lacrimation, fatigue, and onycholysis
      were observed. More recently, a weekly schedule of administration for both drugs
      has been studied. Docetaxel and vinorelbine appear highly active together when
      given on an every-2-week schedule with prophylactic filgrastim, and the
      combination may offer one alter-native to cisplatin-based therapy. However,
      confirmatory phase II and III studies are needed. Certain cumulative toxicities
      (onycholysis, lacrimation) may limit the duration of therapy. Application of this
      regimen for a shorter period, such as in induction or postoperative settings, may
      provide optimal benefit while minimizing toxicity.

PMID- 14725740
TI  - A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy
      for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center
      Affiliate Network (VCCAN) Trial.
AB  - Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical
      studies, probably due to its role as a cell cycle synchronizer for the G2/M
      radiosensitive phase of the cell cycle. We conducted a phase I trial to determine
      the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel
      with concurrent thoracic radiation therapy (TRT) to patients with unresectable
      stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into
      this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion,
      repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were
      escalated in 10 mg/m2 increments in successive cohorts of three new patients, if
      tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or
      hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG)
      toxicity criteria. TRT was administered to the primary tumor and regional lymph
      nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level
      (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was
      expanded to five patients. At the second level (30 mg/m2/week), two out of six
      patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two
      out of four patients developed grade 3 esophagitis and one patient developed
      grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation
      therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary
      toxicity. Other toxicities encountered included skin reaction, nausea and
      vomiting, as well as diarrhea. Additionally, there were no treatment-related
      mortalities or late-occurring toxicities. Esophagitis was the principal DLT of
      concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The
      MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This
      study is still open to accrual with weekly docetaxel and TRT in locally advanced
      NSCLC patients.

PMID- 14725742
TI  - 35th annual ASCO meeting Atlanta, GA.

PMID- 14725747
TI  - Treatment strategies for metastatic non small-cell lung cancer.
AB  - This review article provides evidence to support the use of chemotherapy for non
      small-cell lung cancer (NSCLC). Chemotherapy plays an important role in the
      management of advanced NSCLC. Chemotherapy offers symptom palliation, modest but
      real survival benefits and improves quality of life. The survival benefits
      achieved with newer drug regimens offer chemotherapy as a strategy for the
      treatment of NSCLC patients with good performance, no medical or psychological
      contraindications.

PMID- 14725748
TI  - Positron emission tomography imaging in lung cancer.
AB  - Over the past several years, positron emission tomography (PET) has become a
      clinically useful, noninvasive study which complements conventional imaging
      (chest radiographs, computed tomography [CT], and magnetic resonance imaging
      [MRI]) in the evaluation of patients with lung cancer. PET imaging of lung cancer
      is typically performed with the radiopharmaceutical 18F-2-deoxy-D-glucose (FDG),
      a d-glucose analog. Increased glucose metabolism by malignant cells results in
      increased uptake and accumulation of FDG, which serves as the basis for tumor
      detection. This review will focus on the current applications of FDG-PET in lung
      cancer patients including evaluation of focal pulmonary abnormalities, staging
      lung cancer, determining tumor recurrence, and in assessing prognosis.

PMID- 14725750
TI  - Cancer treatment involving oncolytic viruses.
AB  - Viruses capable of inducing lysis of malignant cells through their replication
      process are known as "oncolytic" viruses. Clinical trials in oncology have been
      performed with oncolytic viruses for nearly fifty years. Both systemic and
      intratumoral routes of administration have been explored. Toxicity has generally
      been limited to injection site pain, transient fever, and tumor necrosis.
      Responses with early crude materials were usually short in duration; however,
      recent trials with gene-attenuated viruses suggest a more prolonged duration of
      responses.

PMID- 14725752
TI  - Prognostic markers in resected stage I and II non small-cell lung cancer: an
      analysis of 260 patients with 5 year follow-up.
AB  - We performed a retrospective analysis of potential prognostic markers in 260
      patients with surgically resected stage I and II non small-cell lung cancer
      (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and
      Wilcoxon tests were employed to analyze the effect of patient characteristics on
      survival and disease-free survival (DFS). In the univariate analysis, the
      following were significant predictors of shorter overall survival: N-stage (N1 vs
      N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence)
      (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs
      negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative)
      (p<0.03). The following were significant predictors of shorter DFS: N-stage
      (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression
      (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression
      (p=0.03). Analysis of survival difference for histologic subtype, degree of
      differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and
      immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E
      cadherin and neuroendocrine markers did not reach statistical significance. In
      multivariate analysis, the following predicted for shorter overall survival: N
      stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for
      DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T
      stage (p=0.05). Of all the clinical-pathological, proliferative, and biological
      markers studied, only a few carried independent prognostic significance.

PMID- 14725754
TI  - Carcinoembryonic antigen peptide-pulsed dendritic cells in patients with
      metastatic cancer.

PMID- 14725755
TI  - Carboplatin and gemcitabine chemotherapy for malignant pleural mesothelioma: a
      phase II study of the GSTPV.
AB  - This study describes the therapeutic effect of carboplatin and gemcitabine in
      combination for malignant pleural mesothelioma (MPM). Twenty patients (14 males
      and 6 females) with a median age of 53 years entered the study. These patients
      had histologically proven MPM with no previous chemo- and/or radiotherapy and
      malignancies. A total of 91 cycles of treatment were administered to 20 patients
      with a median of 4 cycles per patient. A partial response was observed in 4 out
      of 20 patients (20%, 95% confidence interval: 6-43%). No complete responses were
      observed. Only 5 patients (25%) had progressive disease. The response duration
      ranged form 4+ and 21 months.

PMID- 14725756
TI  - Spanning the length scales of biomolecular simulation.

PMID- 14725757
TI  - Induced fit, drug design, and dUTPase.

PMID- 14725758
TI  - FnIII domains: predicting mechanical stability.

PMID- 14725759
TI  - A new catalytic dyad regulates anchoring of molecules to the Gram-positive cell
      wall by sortases.

PMID- 14725760
TI  - Studying topoisomerases in the fourth dimension.

PMID- 14725761
TI  - A closed binding pocket and global destabilization modify the binding properties
      of an alternatively spliced form of the second PDZ domain of PTP-BL.
AB  - PTP-BL is a large phosphatase that is implicated in cellular processes as diverse
      as cytokinesis, actin-cytoskeletal rearrangement, and apoptosis. Five PDZ domains
      mediate its cellular role by binding to the C termini of target proteins, forming
      multiprotein complexes. The second PDZ domain (PDZ2) binds to the C termini of
      the tumor suppressor protein APC and the LIM domain-containing protein RIL;
      however, in one splice variant, PDZ2as, a 5 residue insertion abrogates this
      binding. The insert causes distinct structural and dynamical changes in the
      alternatively spliced PDZ2: enlarging the L1 loop between beta2 and beta3, both
      lengthening and changing the orientation of the alpha2 helix, giving the base of
      the binding pocket less flexibility to accommodate ligands, and destabilizing the
      entire domain. These changes render the binding pocket incapable of binding C
      termini, possibly having implications in the functional role of PTP-BL.

PMID- 14725762
TI  - Tuning the mechanical stability of fibronectin type III modules through sequence
      variations.
AB  - Cells can switch the functional states of extracellular matrix proteins by
      stretching them while exerting mechanical force. Using steered molecular
      dynamics, we investigated how the mechanical stability of FnIII modules from the
      cell adhesion protein fibronectin is affected by natural variations in their
      amino acid sequences. Despite remarkably similar tertiary structures, FnIII
      modules share low sequence homology. Conversely, the sequence homology for the
      same FnIII module across multiple species is notably higher, suggesting that
      sequence variability is functionally significant. Our studies find that the
      mechanical stability of FnIII modules can be tuned through substitutions of just
      a few key amino acids by altering access of water molecules to hydrogen bonds
      that break early in the unfolding pathway. Furthermore, the FnIII hierarchy of
      mechanical unfolding can be changed by environmental conditions, such as pH for
      FnIII10, or by forming complexes with other molecules, such as heparin binding to
      FnIII13.

PMID- 14725763
TI  - Remote phosphate contacts trigger assembly of the active site of DNA
      topoisomerase IB.
AB  - Vaccinia topoisomerase IB forms a covalent DNA-(3'-phosphotyrosyl)-enzyme
      intermediate at its target site 5'-CCCTTp downward arrow in duplex DNA. The
      contributions of backbone electrostatics and individual phosphate oxygens to the
      transesterification reaction were probed by introducing 22 single Rp and Sp
      methylphosphonate diastereomers at 11 positions flanking the cleavage site.
      Methyl groups at eight positions (four on the scissile strand and four on the
      nonscissile strand) inhibited the rate of single-turnover cleavage by factors of
      50-50,000. Stereospecific interference was observed at several phosphates,
      thereby distinguishing simple electrostatic contributions from putative specific
      polar contacts to either the pro-Sp or pro-Rp oxygens. The functionally relevant
      phosphate oxygens are located on the minor groove face of the helix on which the
      scissile phosphodiester resides. Our findings, combined with available crystal
      structures of vaccinia and human topoisomerase IB, show how specific phosphate
      contacts remote from where chemistry occurs are critical for assembly of the
      active site.

PMID- 14725764
TI  - The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP
      binding fold.
AB  - dUTPase is an essential enzyme involved with nucleotide metabolism and
      replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in
      its native conformation and as a complex with dUDP. These reveal a novel protein
      fold that displays no structural similarities to previously described dUTPases.
      The molecular unit is a dimer with two active sites. Nucleotide binding promotes
      extensive structural rearrangements, secondary structure remodeling, and rigid
      body displacements of 20 A or more, which effectively bury the substrate within
      the enzyme core for the purpose of hydrolysis. The molecular complex is a trapped
      enzyme-substrate arrangement which clearly demonstrates structure-induced
      specificity and catalytic potential. This enzyme is a novel dUTPase and therefore
      a potential drug target in the treatment of Chagas' disease.

PMID- 14725765
TI  - Structural basis of diverse substrate recognition by the enzyme PMM/PGM from P.
      aeruginosa.
AB  - Enzyme-substrate complexes of phosphomannomutase/phosphoglucomutase (PMM/PGM)
      reveal the structural basis of the enzyme's ability to use four different
      substrates in catalysis. High-resolution structures with glucose 1-phosphate,
      glucose 6-phosphate, mannose 1-phosphate, and mannose 6-phosphate show that the
      position of the phosphate group of each substrate is held constant by a conserved
      network of hydrogen bonds. This produces two distinct, and mutually exclusive,
      binding orientations for the sugar rings of the 1-phospho and 6-phospho sugars.
      Specific binding of both orientations is accomplished by key contacts with the O3
      and O4 hydroxyls of the sugar, which must occupy equatorial positions. Dual
      recognition of glucose and mannose phosphosugars uses a combination of specific
      protein contacts and nonspecific solvent contacts. The ability of PMM/PGM to
      accommodate these four diverse substrates in a single active site is consistent
      with its highly reversible phosphoryl transfer reaction and allows it to function
      in multiple biosynthetic pathways in P. aeruginosa.

PMID- 14725766
TI  - Molecular basis of proton blockage in aquaporins.
AB  - Water transport channels in membrane proteins of the aquaporin superfamily are
      impermeable to ions, including H+ and OH-. We examine the molecular basis for the
      blockage of proton translocation through the single-file water chain in the pore
      of a bacterial aquaporin, GlpF. We compute the reversible thermodynamic work for
      the two complementary steps of the Grotthuss "hop-and-turn" relay mechanism:
      consecutive transfers of H+ along the hydrogen-bonded chain (hop) and
      conformational reorganization of the chain (turn). In the absence of H+, the
      strong preference for the bipolar orientation of water around the two Asn-Pro-Ala
      (NPA) motifs lining the pore over both unidirectional polarization states of the
      chain precludes the reorganization of the hydrogen-bonded network. Inversely,
      translocation of an excess proton in either direction is opposed by a free-energy
      barrier centered at the NPA region. Both hop and turn steps of proton
      translocation are opposed by the electrostatic field of the channel.

PMID- 14725767
TI  - Crystal structure of human thymidine phosphorylase in complex with a small
      molecule inhibitor.
AB  - Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial
      cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it
      is linked to poor prognosis. HTP expression is utilized for certain
      chemotherapeutic strategies and is also thought to play a role in tumor
      angiogenesis. We determined the structure of HTP bound to the small molecule
      inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI).
      The inhibitor appears to mimic the substrate transition state, which may help
      explain the potency of this inhibitor and the catalytic mechanism of pyrimidine
      nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the
      HTP structure as a template for structure-based drug design by predicting binding
      affinities for TPI and other known HTP inhibitors using in silico docking
      techniques. This work provides the first structural insight into the binding mode
      of any inhibitor to this important drug target and forms the basis for designing
      novel inhibitors for use in anticancer therapy.

PMID- 14725768
TI  - Solution structure of the cyclotide palicourein: implications for the development
      of a pharmaceutical framework.
AB  - The cyclotides are a family of disulfide-rich proteins from plants. They have the
      characteristic structural features of a circular protein backbone and a knotted
      arrangement of disulfide bonds. Structural and biochemical studies of the
      cyclotides suggest that their unique physiological stability can be loaned to
      bioactive peptide fragments for pharmaceutical and agricultural development. In
      particular, the cyclotides incorporate a number of solvent-exposed loops that are
      potentially suitable for epitope grafting applications. Here, we determine the
      structure of the largest known cyclotide, palicourein, which has an atypical size
      and composition within one of the surface-exposed loops. The structural data show
      that an increase in size of a palicourein loop does not perturb the core fold, to
      which the thermodynamic and chemical stability has been attributed. The cyclotide
      core fold, thus, can in principle be used as a framework for the development of
      useful pharmaceutical and agricultural bioactivities.

PMID- 14725769
TI  - Architecture of NarGH reveals a structural classification of Mo-bisMGD enzymes.
AB  - The structure of the catalytic and electron-transfer subunits (NarGH) of the
      integral membrane protein, respiratory nitrate reductase (Nar) has been
      determined to 2.0 A resolution revealing the molecular architecture of this Mo
      bisMGD (molybdopterin-guanine-dinucleotide) containing enzyme which includes a
      previously undetected FeS cluster. Nar, together with the related enzyme formate
      dehydrogenase (Fdh-N), is a key enzyme in the generation of proton motive force
      across the membrane in Escherichia coli nitrate respiration. A comparative study
      revealed that Nar and Fdh-N employ different approaches for acquiring substrate,
      reflecting different catalytic mechanisms. Nar uses a very narrow and nonpolar
      substrate-conducting cavity with a nonspecific substrate binding site, whereas
      Fdh-N accommodates a wider, positively charged substrate-conducting cavity with a
      more specific substrate binding site. The Nar structure also demonstrates the
      first example of an Asp side chain acting as a Mo ligand providing a structural
      basis for the classification of Mo-bisMGD enzymes.

PMID- 14725770
TI  - The structure of sortase B, a cysteine transpeptidase that tethers surface
      protein to the Staphylococcus aureus cell wall.
AB  - Many surface proteins of Gram-positive bacteria, which play important roles
      during the pathogenesis of human infections, are anchored to the cell wall
      envelope by a mechanism requiring sortases. Sortase B, a cysteine transpeptidase
      from Staphylococcus aureus, cleaves the C-terminal sorting signal of IsdC at the
      NPQTN motif and tethers the polypeptide to the pentaglycine cell wall cross
      bridge. During catalysis, the active site cysteine of sortase and the cleaved
      substrate form an acyl intermediate, which is then resolved by the amino group of
      pentaglycine cross-bridges. We report here the crystal structures of SrtBDeltaN30
      in complex with two active site inhibitors, MTSET and E64, and with the cell wall
      substrate analog tripleglycine. These structures reveal, for the first time, the
      active site disposition and the unique Cys-Arg catalytic machinery of the
      cysteine transpeptidase, and they also provide useful information for the future
      design of anti-infective agents against sortases.

PMID- 14725771
TI  - Analyzing protein-DNA recognition mechanisms.
AB  - We present a computational algorithm that can be used to analyze the generic
      mechanisms involved in protein-DNA recognition. Our approach is based on energy
      calculations for the full set of base sequences that can be threaded onto the DNA
      within a protein-DNA complex. It is able to reproduce experimental consensus
      binding sequences for a variety of DNA binding proteins and also correlates well
      with the order of measured binding free energies. These results suggest that the
      crystal structure of a protein-DNA complex can be used to identify all potential
      binding sequences. By analyzing the energy contributions that lead to base
      sequence selectivity, it is possible to quantify the concept of direct versus
      indirect recognition and to identify a new concept describing whether the protein
      DNA interaction and DNA deformation terms select optimal binding sites by acting
      in accord or in disaccord.

PMID- 14725772
TI  - Structural basis for cooperative DNA binding by CAP and lac repressor.
AB  - Catabolite gene activator protein (CAP) and lac repressor (LR) are celebrated
      transcription-regulating proteins that bind to DNA cooperatively forming a
      ternary complex with the promoter loop. Here we present a multiscale model of the
      ternary complex derived from crystal structures of the proteins and a continuous
      structure of the DNA loop built using the theory of elasticity. We predict that
      the loop is underwound in the binary complex with the LR, whereas in the ternary
      complex with the LR and CAP, the loop is overwound and extended due to an
      upstream relocation of a DNA binding hand of LR. The computed relocation distance
      matches the experimental observations and the energy balance of the system
      explains the cooperativity effect. Using the multiscale approach, we build an all
      atom model of the ternary complex that suggests a series of further experimental
      investigations.

PMID- 14725773
TI  - Structural and functional characterization of pi bulges and other short
      intrahelical deformations.
AB  - We data-mined the Protein Data Bank for short intrahelical deformations,
      including pi bulges. These are defined as a contiguous stretch of intrahelical
      residues deviating from the standard alpha-helical i-->i-4 hydrogen bonding
      pattern, bilaterally flanked by at least one alpha-helical turn resulting in a
      helix kink of less than 40 degrees. We find that such motifs exist in 4.7% of a
      PDB subset filtered by quality metrics (resolution <2.5 A, R-factor <0.25,
      sequence identity <35%). These are typically characterized by at least one i-->i
      5 main chain hydrogen bond, with energetically favorable main chain dihedral
      angles, followed by a variable number of main chain carbonyl groups that do not
      accept intrahelical main chain hydrogen bonds. Their stabilization commonly
      occurs via hydrogen bonding to water molecules or polar groups. Numerous
      deformations are implicated in basic yet vital functional roles, commonly as
      ligand binding site contributors.

PMID- 14725774
TI  - Crystal and solution structures of a superantigen from Yersinia
      pseudotuberculosis reveal a jelly-roll fold.
AB  - Superantigens are a class of microbial proteins with the ability to excessively
      activate T cells by binding to the T cell receptor. The staphylococcal and
      streptococcal superantigens are closely related in structure and possess an N
      terminal domain that resembles an OB fold and a C-terminal domain similar to a
      beta-grasp fold. Yersinia pseudotuberculosis produces superantigens, YPMa, YPMb,
      and YPMc, which have no significant amino acid similarity to other proteins. We
      have determined the crystal and solution structures of YPMa, which show that the
      protein has a jelly-roll fold. The closest structural neighbors to YPMa are viral
      capsid proteins and members of the tumor necrosis factor superfamily. In the
      crystal structure, YPMa packs as a trimer, another feature shared with viral
      capsid proteins and TNF superfamily proteins. However, in solution YPMa behaves
      as a monomer, and any functional relevance of the trimer observed in the crystals
      is yet to be established.

PMID- 14725775
TI  - Origins of protein stability revealed by comparing crystal structures of TATA
      binding proteins.
AB  - The crystal structure of TATA binding protein (TBP) from a mesothermophilic
      archaeon, Sulfolobus acidocaldarius, has been determined at a resolution of 2.0 A
      with an R factor of 20.9%. By comparing this structure with the structures of
      TBPs from a hyperthermophilic archaeon and mesophilic eukaryotes, as well as by
      comparing amino acid sequences of TBPs from archaea, covering a wide range of
      optimum growth temperatures, two significant determinants of the stability of TBP
      have been identified: increasing the interior hydrophobicity by interaction
      between three residues, Val, Leu, and Ile, with further differentiation of the
      surface, and increasing its hydrophilicity and raising the cost of unfolding.
      These findings suggest directions along which the stability of TBP can be
      engineered.

PMID- 14725776
TI  - Prison health care: a review of the literature.
AB  - The prison population is increasing and the health problems of prisoners are
      considerable. Prison is designed with punishment, correction and rehabilitation
      to the community in mind and these goals may conflict with the aims of health
      care. A literature review showed that the main issues in prison health care are
      mental health, substance abuse and communicable diseases. Women prisoners and
      older prisoners have needs which are distinct from other prisoners. Health
      promotion and the health of the community outside prisons are desirable aims of
      prison health care. The delivery of effective health care to prisoners is
      dependent upon partnership between health and prison services and telemedicine is
      one possible mode of delivery.

PMID- 14725777
TI  - Comparison of pressure ulcer grading scales: a study of clinical utility and
      inter-rater reliability.
AB  - Pressure ulcer grading scales are subjective measures of pressure damage. This
      study measured inter-observer agreement of the Stirling scale (1-digit and 2
      digit versions) and the European Pressure Ulcer Advisory Panel Scale, using
      Cohen's kappa and percentage agreement. Clinical utility was also assessed.
      Thirty-five observations were made by two Registered Nurses on 30 adult in
      patients. The levels of agreement obtained were better than those reported
      previously and this may be related to the methodology used. The 2-digit Stirling
      scale gave the best level of chance corrected agreement (kappa=0.457) and was the
      scale preferred by raters. The 1-digit Stirling scale performed least favourably.
      Qualitative data identified problems with scale construction relating to
      visualisation of the base of the wound, discolouration of the skin, abrasions and
      shallow ulcers. Whilst refinements in scale construction may improve rater
      reliability, there is a need to develop objective measures of pressure induced
      tissue damage.

PMID- 14725778
TI  - Developing a grounded theory approach: a comparison of Glaser and Strauss.
AB  - Novice qualitative researchers are often unsure regarding the analysis of their
      data and, where grounded theory is chosen, they may be uncertain regarding the
      differences that now exist between the approaches of Glaser and Strauss, who
      together first described the method. These two approaches are compared in
      relation to roots and divergences, role of induction, deduction and verification,
      ways in which data are coded and the format of generated theory. Personal
      experience of developing as a ground theorist is used to illustrate some of the
      key differences. A conclusion is drawn that, rather than debate relative merits
      of the two approaches, suggests that novice researchers need to select the method
      that best suits their cognitive style and develop analytic skills through doing
      research.

PMID- 14725779
TI  - The language of spirituality: an emerging taxonomy.
AB  - BACKGROUND: This paper explores the relationships that exist between the language
      used to describe spirituality within nursing and the appropriateness of
      constructing a universal definition acceptable to all individuals. 'Spirituality'
      is a term that is increasingly used in nursing but there may be problems about
      exactly what the term means and how it is interpreted and understood by both
      nurses and patients. AIM: The aim of the paper is to explore some of the commonly
      cited definitions to establish if the concept of spirituality could be termed
      'universal'. METHOD: This paper presents a discussion, based upon a literature
      review, of the nursing and health care databases, combined with manual searches.
      The review demonstrates how the term spirituality is being constructed within
      nursing suggesting that there are numerous definitions each with several layers
      of meaning. FINDINGS: From the review the authors have developed 'a spiritual
      taxonomy' that may explain and accommodate the different layers of meaning found
      within nursing and health care definitions. At the extreme left there is a
      spirituality based on religious and theist ideals, while at the extreme right
      there is a spirituality based upon secular, humanistic, existential elements. A
      middle way is explained containing elements from both the left and right but not
      as fundamental or radical. CONCLUSION: The authors argue that because there are
      so many definitions with different layers of meanings, spirituality can imply
      different things depending upon an individual's personal interpretation or
      worldview. The results of the review suggest nursing is constructing a 'blanket'
      definition of spirituality, which has a broad, almost inexhaustible set of
      defining characteristics. If this approach continues then there is a danger that
      the word may become so broad in meaning that it loses any real significance.

PMID- 14725780
TI  - How effective are health education programmes--resistance, reactance, rationality
      and risk? Recommendations for effective practice.
AB  - Behavioural-change-related health education programmes represent a mainstay of
      health care activity. Where adopted, however, the theoretical and practical
      constructs and constraints are not always considered. The failure of many health
      education programmes to achieve their intended life-style-related behavioural
      change outcomes is often directly related to the complexity of the task itself.
      Changing a client's health behaviour is notoriously difficult and requires
      concerted and systematic activities to ensure any measure of success. This
      article draws upon existing literature to develop a critical theoretical and
      practical perspective for health education practice in nursing. It aims to
      explore the underpinning theoretical considerations for undertaking behavioural
      change health education programmes. This article also proposes specific
      recommendations for nurse's current and future health education practice, as a
      means for facilitating a more structured approach to health education programme
      planning and evaluation.

PMID- 14725781
TI  - Personal characteristics, health status, physical activity, and quality of life
      in cardiac rehabilitation participants.
AB  - The purpose of this study was to examine the relationships between personal
      factors, health status, and adherence to physical activity behavior, and quality
      of life in cardiac rehabilitation participants. The record of 146 subjects, who
      met inclusion criteria were obtained from the University Cardiac Rehabilitation
      Database. Change scores in physical activity were used as a proxy for adherence.
      Participants who were categorized as not working, female gender, and at high-risk
      health status had lower means and lower improvement scores from repeated measures
      analysis of variance. This study found that some personal factors and health
      status are significant factors influencing the participant's adherence to
      physical activity recommendations and quality of life in this cardiac
      rehabilitation program.

PMID- 14725782
TI  - Nurses' attitudes toward pain treatment with opioids: a survey in a Belgian
      university hospital.
AB  - AIM: To investigate nurses' attitudes toward pain treatment with opioids in a
      Belgian university hospital. METHOD: A cross-sectional, descriptive study design
      was used. The randomised sample included 350 nurses working in the University
      Hospital Leuven, Belgium. Non-response was 10.9%. Nurses' attitudes were explored
      by a structured questionnaire. The score on the opioid attitude scale (OAS)
      varied between 9 and 45. RESULTS: Despite a neutral to positive score on the OAS
      (mean=69.4%), nurses had clearly negative attitudes towards the use of opioids
      during a diagnostic phase and the risk of possible addiction. These negative
      attitudes can hinder adequate pain treatment.

PMID- 14725783
TI  - Evaluation of computer-assisted multimedia instruction in intravenous injection.
AB  - The purpose of this study was to develop a computer-assisted multimedia training
      course for intravenous injection and evaluate its effect on the knowledge and
      self-perceived performance of intravenous injection for novice nurses. Eighty-one
      novice nurses randomly assigned to the experimental group and control group
      participated a designed training procedure and took pretest and posttests. The
      test results were analyzed using statistical methods. From the study it could be
      concluded that the training course had a significant effect on the intravenous
      injection's knowledge. Besides, a high rate of satisfaction for the multimedia
      program showed the self-developed program was successful.

PMID- 14725784
TI  - Validity of pressure ulcer risk assessment scales; Cubbin and Jackson, Braden,
      and Douglas scale.
AB  - This study was to compare the validity of three pressure ulcer risk tools: Cubbin
      and Jackson, Braden, and Douglas scales. Data were collected three times per week
      from 48 to 72 h after admission based on the three pressure ulcer risk assessment
      scales and skin assessment tool developed by the Panel for the Prediction and
      Prevention of Pressure Ulcers (1994) from 112 intensive care unit (ICU) patients
      in a educational hospital Ulsan, Korea during December 11, 2000 to February 10,
      2001. When a patient developed a pressure ulcer at the time of assessment, the
      patient was classified into 'pressure ulcer group', and when patients did not
      have a pressure ulcer until they died, moved to other wards or were discharged
      from the hospital, they were classified into 'not pressure ulcer group'. Four
      indices of validity and area under the curves (AUC) of receiver operating
      characteristic (ROC) were calculated. Based on the cut-off point presented by the
      developer, sensitivity, specificity, positive predictive value, negative
      predictive value were as follows: Cubbin and Jackson scale: 89%, 61%, 51%, 92%,
      respectively, Braden scale: 97%, 26%, 37%, 95%, respectively, and Douglas scale:
      100%, 18%, 34%, 100%, respectively. AUCs of ROC curve were 0.826 for Cubbin and
      Jackson, 0.707 for Braden, and 0.791 for Douglas. Overall, the Cubbin and Jackson
      scale showed the best validity among scales tested and we recommended it for this
      ICU.

PMID- 14725785
TI  - Coping with chronic renal failure in Hong Kong.
AB  - The purpose of the study was to investigate the coping behaviours of Chinese
      patients with chronic renal failure. The study, based on Lazarus and Folkman
      (Stress, Appraisal and Coping, Springer, New York, 1984) model of coping, was
      conducted to identify the process by which 11 chronic renal failure patients cope
      with their disease. The identified themes are coping with fluctuating feelings
      and concerns, motivation to cope, interdependent relationships between patients
      and their family members and modes of coping strategies. The significance of the
      results indicates that coping is the consequence not only of situational demands
      but also of life goals. Meaning in life is an important motivator in the coping
      process. Besides problem-focused coping and emotion-focused coping, another
      important element is relationship-focused coping. The interdependent influences
      of families on patients and patients on families are also important factors. The
      role of family and cultural factors is discussed as it affects how patients with
      chronic renal failure cope with their illness.

PMID- 14725786
TI  - Achieving change in the NHS: a study to explore the feasibility of a home-based
      cancer chemotherapy service.
AB  - A major focus of current health policy in the United Kingdom is the development
      of services that meet the public's expectations. To achieve this there is a need
      to evaluate current provision to ensure that the best use is made of finite
      resources. The study reported here adopted an interview approach to examine an
      existing outpatient chemotherapy service, and to consider the feasibility of
      introducing a home based model. Following a review of literature on this topic
      data were obtained from in-depth interviews with patients and professionals
      regarding the present service. These were then combined with an analysis of
      service contracts and financial estimates. The poor quality of much of the cost
      related information limited the conclusions which could be drawn, and emphasised
      the need for access to more accessible and robust financial information upon
      which to base change. The study also illustrated the benefits of feasibility
      studies; especially when cost-effectiveness and patient satisfaction are the
      driving forces behind proposed changes to clinical services.

PMID- 14725787
TI  - ScFv-mediated in vivo targeting of DAF to erythrocytes inhibits lysis by
      complement.
AB  - Antibodies or antibody fragments represent a powerful class of targeting moieties
      to specifically attach proteins to the surface of a given cell or tissue. Since
      the presence of constant antibody domains in these targeted fusion proteins may
      have certain disadvantages, we report here the reduction of the targeting epitope
      to the variable regions of an Ab by the generation of a single chain antibody
      fragment (scFv). As an effector molecule, we attached the human complement
      regulatory protein (CRP) decay-accelerating factor (DAF) at its amino-terminus
      with a scFv specific for TER-119, a red blood cell (RBC) restricted surface
      antigen of the mouse. This heterologous system enabled us to study (a) the
      applicability of a scFv as a targeting domain, (b) the functionality of the
      effector molecule with respect to regulation of the complement cascade in vitro,
      and (c) the in vivo biodistribution characteristics of a scFv-DAF fusion protein
      attached to a clinically relevant target cell type. RBCs from C57BL/6 mice loaded
      in vitro or in vivo with this fusion protein were significantly protected against
      lysis by human complement. After intravenous injection, a homogeneous population
      of in vivo tagged RBCs was maintained throughout a 6-day follow-up. This result
      and in vitro mixing experiments indicated that there was an equilibration of the
      fusion protein between tagged and non-tagged RBCs. Thus, scFv-mediated targeting
      of proteins to a selected cell or tissue surface has promise as a means to
      supplement absent or defective plasma membrane constituents. This approach should
      therefore be applicable for diseases caused by a membrane protein deficiency such
      as paroxysmal nocturnal hemoglobinuria (PNH).

PMID- 14725788
TI  - Differential substrate and inhibitor profiles for human MASP-1 and MASP-2.
AB  - The mannan-binding lectin (MBL)-associated serine proteases (MASPs) circulate in
      serum complexed with mannan-binding lectin, a recognition molecule of the
      complement system. MASP-2 cleaves the complement components C4 and C2 to form the
      C3 convertase C4b2a. A definitive natural substrate for MASP-1 has not yet been
      described. We investigated the substrate specifities of MASP-1 and MASP-2 using
      cleavage of fluorescent amide substrates by recombinant and serum-derived MASPs.
      Recombinant MASP-1 cleaved Phe-Gly-Arg-aminomethylcoumarin (AMC) most rapidly at
      a rate of 16.8 nmol min(-1) microg(-1) rMASP-1. Recombinant MASP-2 barely cleaved
      any of 14 substrates used. This provides means of measuring MASP-1 activity in
      the absence of a known natural substrate. An assay for MBL-bound MASP-1 was
      established using the substrate Val-Pro-Arg-AMC. Assay of MBL-bound MASP-2 was
      done by cleavage of a natural protein substrate, C4. The condition of the serum
      used for the assays is important; simulated aging showed decreased detectable
      MASP-1 and MASP-2 activity. The inhibitors Z-D-Phe-Pro-methoxy
      propylboroglycinepinanediol ester (boroMpg), anti-thrombin III in the presence
      and absence of heparin, hirudin and C1 inhibitor were tested against the MASPs.
      C1 inhibitor inhibits both enzymes, but the protease-serpin complex is unusually
      unstable at alkaline pH. The thrombin inhibitor boroMpg inhibited MASP-1 but not
      MASP-2 while hirudin did not inhibit either protease. Anti-thrombin III alone was
      not inhibitory, but in the presence of heparin inhibited both MASP-1 and MASP-2.
      The ancient origin of MASP-1 and its thrombin-like activity suggests its
      involvement in a coagulation-based defense mechanism in the early evolution of
      innate immunity.

PMID- 14725789
TI  - Characterization of TCR-induced phosphorylation of PKCtheta in primary murine
      lymphocytes.
AB  - Protein kinase C theta (PKCtheta) is a member of the "novel" PKC subfamily which
      plays a critical role in T-cell activation. Following T-cell stimulation,
      PKCtheta translocates to the center of the immunological synapse where it co
      localizes with the T-cell receptor (TCR). PKCtheta is required for the activation
      of the transcription factors nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1), which regulate the production of interleukin-2 (IL-2), a
      necessary step for the deployment of T-cell effector functions. By using primary
      murine T lymphocytes we have investigated regulatory phosphorylation events on
      PKCtheta which may impinge on its activity or its interaction with other
      signaling mediators. Here, we describe a TCR stimulation-induced Ser/Thr
      phosphorylation event on PKCtheta that takes place simultaneously with its
      recruitment to cellular membranes and which can be detected as an electrophoretic
      mobility shift. By analyzing Ser and Thr point mutants, we find that
      phosphorylation of Ser-695 in the hydrophobic motif is one, but not the only
      residue involved in the mobility shift. Interestingly, Ser-695 appears to be
      required to trigger further phosphorylation events at adjacent Thr-692 and Thr
      703 residues, which also participate in the mobility shift. We show that
      phosphorylation at these residues is not due to auto-phosphorylation, but
      requires instead Src family kinase and phosphatidylinositol 3-kinase (PI3K)
      activities. We further show that activation-induced phosphorylation of PKCtheta
      correlates with its function but not with its kinase activity, suggesting that
      phosphorylation of PKCtheta plays a role in its interaction with upstream or
      downstream effectors.

PMID- 14725790
TI  - Stabilization of peptide guinea pig myelin basic protein 72-85 by N-terminal
      acetylation-implications for immunological studies.
AB  - Peptide gpMBP72-85, containing amino acids 72-85 of guinea pig myelin basic
      protein is commonly used to induce experimental autoimmune encephalomyelitis in
      Lewis rats. The N-terminal glutamine in this peptide can cyclize to pyroglutamic
      acid, leading to loss of the first MHC anchor for binding to MHC class II.
      Acetylation of the peptide N-terminus prevents pyroglutamic acid formation and
      ensures a constant quality. An increased MHC binding affinity after N-terminal
      acetylation was observed. This modification also enhanced T cell proliferation of
      a gpMBP reactive T cell clone. The encephalitogenicity of peptide gpMBP72-85 was
      unaffected by acetylation. It is concluded that acetylation improves the chemical
      stability of gpMBP72-85, and is not detrimental but rather favorable for its
      biochemical and immunological, in vitro, and in vivo behavior.

PMID- 14725791
TI  - HIV-1 induces complement factor C3 synthesis in astrocytes and neurons by
      modulation of promoter activity.
AB  - Virus-induced complement expression and activation in the brain is hypothesized
      to contribute to the process of neurodegeneration in AIDS-associated neurological
      disorders. Previous experiments have shown that the human immunodeficiency virus
      (HIV) upregulates the low basal production of complement factor C3 in astrocytes
      and neurons. Since inhibition of complement synthesis and activation in the brain
      may represent a putative therapeutic goal to prevent virus-induced damage, we
      analysed the mechanism of the HIV-induced modulation of C3 expression. Detailed
      studies using different C3 promoter constructs revealed that HIV activates the
      synthesis of C3 by stimulation of the promoter. This HIV-induced promoter
      activation could be measured both in different astrocytic cell lines and in
      neurons. Deletion constructs of the C3 promoter defined the IL-6/IL-1beta
      responsive element within the promoter region as a central element for the
      responsiveness of the C3 promoter towards the influence of HIV. A binding site
      for the transcription factor C/EBPdelta was identified as important regulatory
      domain within the IL-6/IL-1beta responsive element, since a point mutation which
      eliminates the binding capacity of C/EBPdelta to this site also abolishes the
      induction by HIV-1. Similarly, the viral proteins Nef and gp41 which had also
      been shown to stimulate the synthesis of C3, exert their effect via the IL-6/IL
      1beta responsive element with binding of the transcription factor C/EBPdelta
      representing the critical step. Our experiments clearly define the mechanism for
      the induction of complement factors in the HIV-infected brain and reveal a
      decisive role of the regulator protein C/EBPdelta for the HIV-induced increase in
      C3 expression.

PMID- 14725792
TI  - Structural analysis of the epitopes on erbB2 interacted with inhibitory or non
      inhibitory monoclonal antibodies.
AB  - erbB2 oncogene encodes a growth factor receptor. The overexpression of erbB2 was
      correlated with more aggressive tumors and a poorer prognosis. Some antibodies
      directed to this molecule have an antitumor effect in vivo, but some antibodies
      do not. In an attempt to understand the molecular basis of the anti-erbB2
      antibody interaction with erbB2 ectodomain (ECD), we analyzed binding epitopes on
      erbB2 for inhibitory and non-inhibitory antibodies, Herceptin and HF by computer
      guided protein engineering and site-directed mutagenesis. Two different
      interaction domains were identified by molecular docking, computer graphics and
      distance geometry method and confirmed through studies on a series of mutants of
      erbB2 ECD. Non-inhibitory antibody HF only recognized N-terminal portion of erbB2
      ECD, but inhibitory antibody Herceptin bound to C-terminal portion of it
      exclusively. The region interacted with inhibitory antibody Herceptin can be an
      important target for anticancer therapies.

PMID- 14725793
TI  - Molecular profile of the T cell receptors of regulatory and effector CD4+ T cells
      recognizing overlapping determinants on glutamic acid decarboxylase (524-543).
AB  - Glutamic acid decarboxylase (GAD65) is one of the autoantigens that initiates
      pathogenic T cell responses against insulin-secreting pancreatic beta cells in
      Type 1 diabetes (T1D). Previously it was shown that spontaneously arising
      pathogenic T cell responses in the NOD mouse model are confined to GAD530-543
      (p530). However, regulatory T cell subpopulations, which can prevent diabetes,
      can also be generated, for example, by immunization with GAD524-538 (p524) or
      GAD524-543. Interestingly, two functionally distinct subpopulations of T cells
      which recognize overlapping determinants of GAD524-543, p524 and p530, utilize
      distinct TCR Vbeta families, Vbeta4 for pathogenic, and Vbeta12 for regulatory T
      cells. We characterized T cell receptors (TCRs) from each subpopulation of T
      cells and visualized p524-specific TCR/p524/I-A(g7) and p530-specific TCR/p530/I
      A(g7) complexes via molecular modeling to help us understand, at a molecular
      level, the in vivo expansion of p524- or p530-specific T cells in the NOD model
      of T1D. The absolute restriction in Vbeta usage but not Valpha usage and
      conserved CDR3beta lengths for both T cell subpopulations demonstrates that the
      beta chains are main contributors in shaping both p524/I-A(g7) and p530/I-A(g7)
      restricted TCRs. However, only Vbeta4+ T cells but not Vbeta12+ T cells contain a
      common motif (DWG) in CDR3beta and may involve all of CDR1beta, CDR2beta, and
      CDR3beta in the recognition of the C-terminus of p530. These observations imply
      that the spontaneously arising p530-restricted TCRs may be selected under
      stringent structural frameworks to bind p530/I-A(g7) with high affinity. Thus,
      the pathogenic p530-specific T cells may arise from a small pool of autoreactive
      T cells upon breaking tolerance.

PMID- 14725794
TI  - Network for auditory intrinsic alertness: a PET study.
AB  - Intrinsic alertness designates the internal (cognitive) control of wakefulness
      and arousal; typical tasks to assess optimal levels of intrinsic alertness are
      simple reaction time (RT) measurements without preceding warning stimuli. Until
      now, cerebral networks subserving alertness after visual and somatosensory
      stimulation have been reported. Studies concerning other intensity aspects of
      alertness like sustained attention and vigilance, on the other hand, have been
      performed in the auditory modality, too. In a 15O-butanol PET-activation study in
      10 right-handed young healthy male volunteers an intrinsic alertness network was
      studied for the auditory modality. In contrast with a sensorimotor control
      condition we found an extended predominantly right-hemisphere network similar to
      those reported for other sensory modalities including frontal, cingular, inferior
      parietal, temporal and thalamic structures, when subjects waited for and rapidly
      responded to a 1000 Hz tone signal by pressing a response key with the right-hand
      thumb. There were, however, some differences in the topography of the frontal,
      temporal and thalamic activations between auditory and visual stimulation which
      are discussed with respect to similar results for auditory vigilance and auditory
      selective attention tasks reported in the literature.

PMID- 14725795
TI  - Saccade dysmetria in Williams-Beuren syndrome.
AB  - Numerous studies have described the poor visuo-spatial processing capacities of
      subjects with Williams-Beuren syndrome (WBS), a genetically based developmental
      disorder. Since visual perception and eye movements are closely related we
      hypothesized that the poor visuo-spatial processing capacities of subjects with
      WBS might be related to a poor saccadic control. Thereto, we recorded horizontal
      and vertical saccadic eye movements to targets using infrared video-oculography
      in 27 subjects with WBS and eight healthy controls. In the WBS group saccadic
      gains were highly variable, both between and within individual subjects, and they
      often needed more than one correction saccade to reach the target. Ten (out of a
      subgroup of 22) WBS subjects showed a large number of hypometric and/or
      hypermetric saccades, and, also a left-right asymmetry in saccadic gains was
      observed in WBS. We conclude that the observed impairments in saccadic control
      are likely to affect the proper processing of visuo-spatial information.

PMID- 14725796
TI  - Visual inspection time in Parkinson's disease: deficits in early stages of
      cognitive processing.
AB  - Inspection time (IT) is a simple information processing paradigm dependent on a
      participant's ability to identify physical properties of a stimulus presented for
      a specified time interval. In contrast with reaction time (RT) studies, the
      dependent variable of interest in IT is not related to the motoric speed with
      which the individual is able to respond, but rather the minimum presentation time
      necessary for participants to reliably identify physical properties of the
      stimulus. It is well documented that individuals with Parkinson's disease (PD)
      experience significant impairment on tests of simple RT, but it is unclear
      whether such deficits can be interpreted as 'pure' slowness of information
      processing, or a delay in the selection and output of a motor response. In the
      first experiment described here, a sample of 'optimally medicated' PD patients
      was compared with an age-matched control group, on an IT task. Results of this
      experiment suggested that individuals with PD required significantly longer
      stimulus presentation times than healthy participants. The second experiment
      compared a sample of PD patients (tested both "ON" and "OFF" their typical
      dopaminergic medications), with an age-matched control group, on the same test of
      IT. Results again indicated a significant IT deficit in participants with PD, and
      suggested that these deficits do not significantly resolve with levodopa
      treatment. Overall, the results of these two experiments suggest that information
      processing deficits associated with PD are distinct from motor impairment. These
      findings are further discussed in terms of existing neurochemical models of
      information processing ability.

PMID- 14725797
TI  - The semantic organisation of proper nouns: the case of people and brand names.
AB  - We describe the performance of a patient (AZ) with a semantic refractory access
      disorder on a series of experiments probing comprehension of two broad proper
      noun categories, namely person names and brand names. By inducing and
      manipulating the semantic relatedness effects which are commonly observed in
      semantic refractory access patients, we demonstrate that famous person knowledge
      is primarily organised by occupation, whilst knowledge of brands is organised by
      product type. For instance, we show that AZ has significantly greater difficulty
      identifying a famous person from among distractor personalities who have the same
      occupation (e.g. composers: Beethoven, Mozart, Handel, and Bach) than those who
      have different occupations (e.g. Beethoven, Picasso, Shakespeare, and Jefferson).
      We also show that such semantic relatedness effects do not occur when stimuli are
      grouped by another variable such as nationality. We argue that these semantic
      distance effects reflect the greater build-up of refractoriness among concepts
      which are supported by shared neural circuitry. In psychological space, it seems
      natural that these individuals should be classified in this way. The strength of
      our findings lie in the fact that this organisation of psychological space is
      mirrored by neural organisation. Thus, we report a previously undocumented degree
      of fine-grain organisation within conceptual knowledge of these classes of proper
      nouns. We also interpret our data as providing the strongest empirical support to
      date for the semantic module of cognitive models of person recognition.

PMID- 14725798
TI  - Evidence for perceptual deficits in associative visual (prosop)agnosia: a single
      case study.
AB  - Associative visual agnosia is classically defined as normal visual perception
      stripped of its meaning [Archiv fur Psychiatrie und Nervenkrankheiten 21 (1890)
      22/English translation: Cognitive Neuropsychol. 5 (1988) 155]: these patients
      cannot access to their stored visual memories to categorize the objects
      nonetheless perceived correctly. However, according to an influential theory of
      visual agnosia [Farah, Visual Agnosia: Disorders of Object Recognition and What
      They Tell Us about Normal Vision, MIT Press, Cambridge, MA, 1990], visual
      associative agnosics necessarily present perceptual deficits that are the cause
      of their impairment at object recognition Here we report a detailed investigation
      of a patient with bilateral occipito-temporal lesions strongly impaired at object
      and face recognition. NS presents normal drawing copy, and normal performance at
      object and face matching tasks as used in classical neuropsychological tests.
      However, when tested with several computer tasks using carefully controlled
      visual stimuli and taking both his accuracy rate and response times into account,
      NS was found to have abnormal performances at high-level visual processing of
      objects and faces. Albeit presenting a different pattern of deficits than
      previously described in integrative agnosic patients such as HJA and LH, his
      deficits were characterized by an inability to integrate individual parts into a
      whole percept, as suggested by his failure at processing structurally impossible
      three-dimensional (3D) objects, an absence of face inversion effects and an
      advantage at detecting and matching single parts. Taken together, these
      observations question the idea of separate visual representations for object/face
      perception and object/face knowledge derived from investigations of visual
      associative (prosop)agnosia, and they raise some methodological issues in the
      analysis of single-case studies of (prosop)agnosic patients.

PMID- 14725799
TI  - A method for studying the evolution of naming error types in the recovery of
      acute aphasia: a single-patient and single-stimulus approach.
AB  - In this study, we present a method for analysing the evolution of picture naming
      errors in the follow-up of single patients affected by acute aphasia. In
      particular, we have based our analysis on the presence of response type
      inconsistency, as patients often fail to give the same type of response to the
      same stimulus at a task repetition attempted after a short time. Due to the
      uncertain definition of the type of response associated to a given stimulus for
      each stage of the clinical course, the investigation of the factors underlying
      the transition between different types of response is a serious methodological
      challenge. The solution presented here is based on a multiple presentation of the
      same naming battery at different stages of the clinical course, on the estimation
      of the probability associated with each response type at each stage, and on the
      estimation of the transition probability between different response types from
      one clinical stage to another. The basic idea was to use the set of probabilities
      referred to above as single stimuli weights in the study of linear models; these
      permit to compare different types of responses and different types of
      transitions. We present the application of this method to the study of a single
      case, a woman affected by fluent aphasia examined twice in the first 2 weeks
      following stroke. Besides discussing empirical findings, we comment on the
      usefulness of this method for wider fields of inquiry.

PMID- 14725800
TI  - Effect of intention and visual fixation disengagement on prosaccades in
      Parkinson's disease patients.
AB  - In a previous study, we postulated a divergence in reflexive versus voluntary
      saccade behavior in Parkinson's disease (PD) patients and hypothesized a fronto
      striatal dysfunction. The voluntary saccade tasks included antisaccades (AS) and
      remembered saccades (RemS). However, multiple cognitive processes are involved in
      AS and RemS and the procedures lack a visual target. The present study had two
      main objectives. Firstly, we wanted to extend our previous findings of disturbed
      AS and RemS to other intentional (endogenous, "voluntary") saccades but now with
      a visible target. Therefore, an intentional prosaccade (IpS) task was used.
      Secondly, we investigated whether there is a different saccade behavior in PD
      patients and controls in conditions where the central fixation stimulus is
      extinguished shortly before the onset of the peripheral target (the so called gap
      condition) to assess the role of disengagement of visual fixation. With respect
      to the first objective, the present study found a clear dissociation between the
      performances of PD patients on reflexive saccade (RS) versus IpS tasks. Patients
      did not differ from controls in latency or error rate of RS. However, in the IpS
      task, latency was longer and error rate was higher in PD patients. Thus, the
      present study provides evidence that PD patients are deficient in intentional
      saccade tasks independent from the fact whether a target is visible or not. As to
      the second objective, saccades of PD patients did show a shorter latency in the
      gap than in the no gap condition. This suggests that the gap effect is not
      dominantly dependent on nigro-collicular neuronal circuits that are affected in
      PD. In the patients, the gap effect was reliable in the RS task, but not in the
      IpS condition. These discordant gap findings might suggest modulation of selected
      neuronal circuits involved in early sensorimotor processing. The present findings
      do not to support the hypothesis that impaired saccade behavior in PD patients is
      merely dependent on the presence or the absence of visual fixation and suggests a
      higher order psychomotor dysfunction, presumably of intentional nature. The
      dorsolateral prefrontal cortex might correspond to the premotor cognitive
      dysfunction site. However, an additional involvement of the frontal eye field can
      not be excluded from the present study.

PMID- 14725801
TI  - Patient Schn: has Goldstein and Gelb's case withstood the test of time?
AB  - The current manuscript takes a critical look at the case of Goldstein and Gelb's
      patient, Schn, reported to be the first well-defined example of apperceptive
      visual agnosia. While doubts have been cast on the validity of the original
      investigations, we propose that perhaps the case of Schn should be reclassified
      as an example of integrative agnosia. Be that as it may, what is not in doubt is
      that the case of Schn has had a lasting impact on the development of
      neuropsychological theorem.

PMID- 14725802
TI  - A category-specific advantage for numbers in verbal short-term memory: evidence
      from semantic dementia.
AB  - This study explored possible reasons for the striking difference between digit
      span and word span in patients with semantic dementia. Immediate serial recall
      (ISR) of number and non-number words was examined in four patients. For every
      case, the recall of single-digit numbers was normal whereas the recall of non
      number words was impaired relative to controls. This difference extended to multi
      digit numbers, and remained even when frequency, imageability, word length, set
      size and size of semantic category were matched for the numbers and words. The
      advantage for number words also applied to the patients' reading performance.
      Previous studies have suggested that semantic memory plays a critical role in
      verbal short-term memory (STM) and reading: patients with semantic dementia show
      superior recall and reading of words that are still relatively well known
      compared to previously known but now semantically degraded words. Additional
      assessments suggested that this semantic locus was the basis of the patients'
      category-specific advantage for numbers. Comprehension was considerably better
      for number than non-number words. Number knowledge may be relatively preserved in
      semantic dementia because the cortical atrophy underlying the condition typically
      spares the areas of the parietal lobes thought to be crucial in numerical
      cognition but involves the inferolateral temporal-lobes known to support general
      conceptual knowledge.

PMID- 14725803
TI  - How 'generalized' is the 'slowed processing' in SLI? The case of visuospatial
      attentional orienting.
AB  - The study was designed to assess the speed and efficiency of visuospatial
      attentional orienting and the speed of visual processing and motor response in
      school-age children diagnosed with specific language impairment (SLI). Fifteen
      participants with SLI (7-15 years old) and their gender- and age-matched normally
      developing peers performed two formats of a simple visual discrimination task,
      one requiring the use of attentional orienting for accurate performance, and the
      other not requiring shifts of attention. The SLI group was characterized by (a)
      slower visual processing, and (b) slower motor response, but (c) similar
      attentional orienting speed, relative to the control group. The results are
      discussed in relation to the 'generalized slowing hypothesis' in SLI and the
      neural underpinning of visuospatial attentional orienting and SLI.

PMID- 14725804
TI  - Recall and recognition in mild hypoxia: using covariance structural modeling to
      test competing theories of explicit memory.
AB  - To test theories of explicit memory in amnesia, we examined the effect of hypoxia
      on memory performance in a group of 56 survivors of sudden cardiac arrest.
      Structural equation modeling revealed that a single-factor explanation of recall
      and recognition was insufficient to account for performance, thus contradicting
      single-process models of explicit memory. A dual-process model of recall in which
      two processes (e.g., declarative memory and controlled search) contribute to
      recall performance, whereas only one process (e.g., declarative memory) underlies
      recognition performance, also failed to explain the results adequately. In
      contrast, a dual-process model of recognition provided an acceptable account of
      the data. In this model, two processes--recollection and familiarity--underlie
      recognition memory, whereas only the recollection process contributes to free
      recall. The best-fitting model was one in which hypoxia and aging led to deficits
      in recollection, but left familiarity unaffected. Moreover, a controlled search
      process was correlated with recollection, but was not associated with familiarity
      or the severity of hypoxia. The results support models of explicit memory in
      which recollection depends on the hippocampus and frontal lobes, whereas
      familiarity-based recognition relies on other brain regions.

PMID- 14725805
TI  - Cerebral lateralization in schizophrenia and dyslexia: neuromagnetic responses to
      auditory stimuli.
AB  - Many studies have shown altered hemispheric asymmetry-particularly in perisylvian
      regions-in schizophrenia patients as well as in individuals with dyslexia. Here
      we explore the similarity of these findings comparing the localization of the
      magnetic auditory N100m to the German syllable [ba:] in schizophrenia patients,
      dyslexic adults, and healthy control subjects. Control subjects showed the
      typical finding of more anterior sources in the right than in the left
      perisylvian region. In contrast, both schizophrenia patients and dyslexic
      subjects displayed a symmetrical N100m source configuration. While in people with
      dyslexia the alteration appears to originate in the right hemisphere, left
      hemispheric deviations might contribute to reduced asymmetry in schizophrenia
      patients. Our results indicate that an absence of lateralized auditory responses
      in the temporal lobes may reflect a common deviance present in dyslexia and
      schizophrenia. The nonspecific finding of reduced cerebral laterality may be
      accounted for by population-specific differences in the functional organization
      of perisylvian sites.

PMID- 14725806
TI  - Hemodynamic differences in the activation of the prefrontal cortex: attention vs.
      higher cognitive processing.
AB  - Both simple attention tasks (e.g. letter cancellation) and most tasks of higher
      cognitive processing (e.g. word generation) are known to activate the
      dorsolateral prefrontal cortex (PFC). While attention and higher cognitive
      processing differ phenomenologically, with attention tasks requiring great
      subjective effort despite their simplicity, possible physiological differences in
      the activation of the PFC between the two types of cognitive processing have
      remained uninvestigated. Hemodynamic changes in the PFC during activation due to
      tasks of attention and those of higher cognitive processing were examined using
      near-infrared spectroscopy in 10 Japanese and 10 American healthy adults. In
      tasks of higher cognitive processing, which included both verbal and non-verbal
      tasks, the concentration of oxygenated hemoglobin ([HbO2]) increased, and that of
      deoxygenated hemoglobin ([HbR]) decreased, with an increase in the tissue
      hemoglobin saturation (THS). In tasks of attention, which consisted of the letter
      cancellation and continuous performance test, both [HbO2] and [HbR] increased,
      with no significant changes in the THS observed. The distinctive patterns of
      hemodynamic changes were not affected by the factors of task difficulty or
      language. The change in [HbR] may be a physiological marker of the prefrontal
      lobe activation that discriminates between attention and higher cognitive
      processing. The increase in [HbR] suggests increased oxygen consumption of the
      PFC during tasks of attention, which might be related to the disproportionately
      great subjective effort associated with sustained attention. The physiological
      alteration in hemodynamic patterns according to changes in cognition needs to be
      examined in subjects with prefrontal lobe dysfunction, such as schizophrenia and
      mood disorder.

PMID- 14725807
TI  - Growth stimulation of mandibular condyles and femoral heads of newborn rats by
      IGF-I.
AB  - Primary and secondary cartilage differ in embryonic origin and are generally
      considered to have a different mode of growth. However, few experimental studies
      exist that directly compare the two types of cartilage and their growth
      regulation. The regulation of cartilage growth is a complex mechanism involving
      growth factors like insulin-like growth factor-I (IGF-I). The purpose of this
      study was to compare the growth of mandibular condyles of 4-day-old rats with
      that of femoral heads in vitro and to analyze the effects of IGF-I. Explants were
      cultured for up to 2 weeks with 0, 5, and 25 ng/ml IGF-1. Both, 5 and 25 ng/ml
      IGF-I significantly stimulated growth of the mandibular condyles while only 25
      ng/ml IGF-I stimulated growth of the femoral heads. IGF-I increased
      glycosaminoglycan synthesis of both condylar and femoral cartilage. However, only
      the DNA synthesis of the mandibular condyles was significantly increased by IGF-I
      while that of the femoral heads was not affected. It is concluded that IGF-I
      stimulates growth of both secondary condylar cartilage and primary femoral
      cartilage. The mandibular condyle appears to be more sensitive to IGF-I than the
      femoral head, which may partly be due to the different developmental stage.

PMID- 14725808
TI  - Human minor and major gland saliva proteins and ability to mediate Actinomyces
      naeslundii adherence.
AB  - Bacteria-binding components and the ability to mediate bacterial adhesion to the
      tooth surface have been thoroughly studied in major salivary gland secretions.
      Our knowledge on the bacteria binding activity in minor gland saliva is, however,
      limited. In this study, proteins were examined in parallel in minor (palatal,
      buccal and labial) and major (parotid and submandibular/sublingual) salivary
      gland secretions in one subject using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) and immunoblotting. The adherence of early colonizing
      Actinomyces naeslundii to pellicles formed from the secretions on hydroxyapatite
      beads was also examined. Amylase, IgA, proline-rich proteins and the high
      molecular-weight glycoproteins, agglutinins, were detected in all saliva tested.
      Carbohydrate-reactive antibodies recognized the low-molecular weight mucin, MUC 7
      in submandibular/sublingual saliva only. A. naeslundii strain 12104 adhered to
      all pellicles and especially to the buccal gland saliva pellicles. Strain LY7
      adhered in highest numbers to the submandibular/sublingual saliva pellicles. It
      also bound in considerable numbers to parotid and palatal saliva pellicles but
      not to the ones formed from buccal and labial gland saliva. Our findings indicate
      that several bacteria-binding components are secreted in both minor and major
      gland saliva. The adherence-promoting ability of the various gland secretions
      differs, however.

PMID- 14725809
TI  - Neural regulation of submandibular gland blood flow in the streptozotocin
      diabetic rat: evidence for impaired endothelium-dependent vasodilatation.
AB  - Functional changes in vascular tone and reactivity arise early in diabetes, and
      endothelial dysfunction plays a central role in the development of these
      microvascular abnormalities. Blood flow in the rat submandibular gland is mainly
      under neural regulation, which is mediated in part via endothelium-dependent
      mechanisms. Given the role of the endothelium in regulating blood flow and the
      deleterious effects of diabetes on endothelial cell function, we hypothesised
      that diabetes would significantly impair neural regulation of submandibular gland
      vascular perfusion. Three weeks after the induction of streptozotocin diabetes
      continuous 2 Hz sympathetic stimulation resulted in a similar degree of
      vasoconstriction (as measured by a decrease in perfusion) in both diabetic (-31+/
      17%) and control rats (-22+/-7%). However, the magnitude and the duration of the
      after-dilatation were significantly less in diabetic animals. The same number of
      impulses delivered at 20 Hz in bursts (1s in every 10s) also resulted in
      vasoconstriction with each burst, but unlike the effects of burst stimulation in
      control rats the initial vasoconstriction was not converted to a net
      vasodilatation between bursts. Parasympathetic stimulation (2, 5 and 10 Hz)
      caused a marked vasodilatation in both control and diabetic rats, but the initial
      responses were delayed in diabetic animals, the maintained phases were smaller in
      magnitude (P<0.02) and it took longer to return to resting levels. In conclusion,
      submandibular gland vascular responses are altered in streptozotocin-induced
      diabetic rats. Vasoconstrictor responses evoked by sympathetic impulses were
      unaffected, but vasodilatory responses, particularly those associated with
      endothelium-dependent mechanisms, were significantly reduced.

PMID- 14725810
TI  - Comparison of single and multiple sieve methods for the determination of
      masticatory performance.
AB  - In the majority of studies on masticatory performance, the degree of food
      breakdown has been determined by sieving the food with one or more sieves. The
      aim of the present study was to compare the results obtained with a single and a
      multiple sieve method, as these methods have never been compared. We analysed the
      chewed food of 176 dentate subjects with a single and a multiple sieve method.
      Furthermore, we quantified the influence of age, gender, and dental status on the
      masticatory performance in order to compare the sensitivity of both methods. We
      observed a significant influence of the number of occlusal units on the
      masticatory performance for both methods. The single sieve method is less
      reliable than the multiple sieve method if the sieve diameter is not close enough
      to the median particle size of the chewed food. Therefore, we recommend the
      multiple sieve method.

PMID- 14725811
TI  - Demineralization in enamel and hydroxyapatite aggregates at increasing ionic
      strengths.
AB  - Subsurface demineralization of dental enamel is a curious feature of both in vivo
      and in vitro lesion formation. Numerous explanations have been proposed to
      explain this. One general hypothesis is that subsurface demineralization in
      enamel and synthetic hydroxyapatite (HAP) aggregates may result from the
      phenomenon of coupled diffusion between the inward transport of acid and the
      outward transport of dissolution products. The aim of this study was to test the
      validity of this explanation. Inert electrolyte was added to demineralizing
      solutions in order to reduce electrostatic coupling between the diffusive flows
      that occur during lesion formation. Scanning microradiography (SMR) was used to
      examine surface layer formation, and to measure the rate of mineral loss at
      increasing ionic strengths. It was found that surface layer formation was
      significantly reduced as the concentration of inert electrolyte was increased.
      Further, the rate of mineral loss from the developing lesion increased as the
      concentration of inert electrolyte (and therefore the ionic strength) in the
      demineralizing solution increased. It is concluded that electrostatic coupling
      between counter diffusing acid and dissolution products during lesion formation
      can significantly influence the mineral concentration within the surface layer.

PMID- 14725812
TI  - The effect of partial damage to the enamel-related periodontium combined with
      root resection on eruption of the rat incisor eruption.
AB  - Previous work has indicated that the enamel-related periodontium (ERP) has a role
      in the eruptive process of the rat lower incisor. By combining partial damage of
      this tissue with resection of the odontogenic organ, we examined the effect of
      the damage on subsequent incisor eruption. The connective tissue of the enamel
      related periodontium was regenerated in less than 2 weeks, showing morphology
      close to normal. The injured part of the enamel organ was neither regenerated nor
      repaired, and a cement-like tissue, continuous with the true acellular cement,
      was formed on the denuded enamel. Before tooth exfoliation, the operated teeth
      erupted at a slower rate compared with root-resected and sham-operated incisors,
      probably because of the absence of a substantial part of the enamel organ due to
      surgical damage. As with the coronal dental follicle and the enamel organ in rat
      molars, the enamel-related periodontium and the enamel organ of rat incisors may
      have some control on their eruptive process.

PMID- 14725813
TI  - The mesiodistal crown diameters of primary dentition in Indonesian Javanese
      children.
AB  - Dentition analysis of primary teeth is necessary for recognising and correcting
      occlusal problems in every stage of dental development to enable normal adult
      occlusion. To do this, normative data of mesiodistal tooth crown diameters from
      the same ethnic population are needed. The aims of this study were to gather
      normative data of mesiodistal crown diameters of primary dentition in Indonesian
      Javanese children and to compare this normative data with published data of other
      ethnic populations. Dental casts of 160 males and 137 females with acceptable
      occlusion, aged 3.25-6.58 years, were taken in Yogyakarta, Indonesia. Mesiodistal
      diameter was measured as the distance between the anatomic contact points using
      calipers with accuracy to within 0.05 mm. Each measurement was taken twice on
      different occasions. The results indicated that the magnitude of asymmetry
      between right and left teeth was larger in distal teeth within a tooth field,
      larger in males than females, and larger in mandibular than maxillary teeth. The
      stability of mesiodistal tooth crown diameters was less in males than in females,
      and was most prominent in the mandibular central incisor. Sexual dimorphisms were
      found in, the lateral incisor and first molar in the maxilla, and the canine,
      first and second molars in the mandible. Compared with other ethnic populations,
      Indonesian Javanese falls between Hong Kong Chinese and Australian Aboriginal.

PMID- 14725814
TI  - Pharmacological properties of serotonin receptor subtypes mediating contraction
      of bovine inferior alveolar arteries.
AB  - OBJECTIVE: To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes
      mediating contraction of the inferior alveolar artery. Additionally, to determine
      the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase
      and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT.
      METHODS: Contractile responses to 5-HT were examined in vitro using ring segments
      of bovine inferior alveolar arteries. Affinity constants (K(B)'s) of subtype
      selective 5-HT receptor antagonists were determined to characterise the 5-HT
      receptor-subtypes causing contraction of inferior alveolar arteries. RESULTS: In
      100 nM ketanserin or 30 nM spiperone, 5-HT caused a biphasic contraction best-fit
      by a two-site curve model, where one site was antagonist-sensitive and the other
      site antagonist-insensitive. 5-HT(2A) receptor-subtype selective antagonists,
      ketanserin and spiperone, blocked 5-HT induced contraction with K(B)'s of 1.0 and
      0.16 nM, respectively. RS102221 (5-HT(2C) selective) and (S)-WAY100135 (5-HT(1A)
      selective) blocked 5-HT stimulated contraction with low affinities (K(B)'s=100 nM
      and 330 nM, respectively). GR55562, a 5-HT(1) receptor subtype antagonist with a
      reported affinity of 500 nM at the 5-HT(1D) receptor subtype, blocked 5-HT
      induced contraction with a K(B) of 470 nM. Cylooxygenase inhibition with 50
      microM ibuprofen caused a 44% increase in maximal contraction to 5-HT; whereas,
      nitric oxide inhibition with N(G)-nitro-L-arginine, endothelium removal or
      inhibition of 5-HT uptake and monoamine oxidase with imipramine and iproniazid,
      respectively, did not affect 5-HT contraction. CONCLUSIONS: Both 5-HT(2A) and 5
      HT(1D/1B) receptor subtypes mediate 5-HT induced contraction of the bovine
      inferior alveolar artery. 5-HT stimulated contraction of the inferior alveolar
      artery is modulated by a vasodilator prostaglandin.

PMID- 14725815
TI  - Dental discolouration after thermal treatment.
AB  - Enamel and dentin discolouration have extrinsic and intrinsic origins. Possible
      causes include pigmented food or drink, caries, clinical chemical treatments,
      trauma and, high temperature. In the oral cavity, dental hard tissues can be
      heated when irradiated with high-intensity lasers. This paper, reports initial
      results on the discolouration of enamel and dentin induced by thermal treatment.
      The samples used in this work were bovine incisor teeth. Enamel and dentin
      discolouration were verified using microscopy and transmission spectroscopy.
      Thermal treatment was carried out at temperatures of 140 and 200 degrees C. The
      natural transparent aspect of the enamel became opaque after thermal treatment,
      it whitened following treatment at 140 degrees C, and turned completely opaque
      after treatment at 200 degrees C. With the same thermal treatment, dentin became
      light brown after treatment, at 140 degrees C, and the brown pattern was more
      evident after treatment at 200 degrees C. Although there is no conclusive
      evidence, non-enzymatic browning, collagen denaturation or oxidation of some
      chemical component of the dentin, may be intensified or produced by the thermal
      treatment. In enamel, water loss and the consequent increase in light scattering
      explain the observed opacity.

PMID- 14725816
TI  - Effect of phosphophoryn on rhBMP-2-induced bone formation.
AB  - In the present study, dentin phosphophoryn (DPP) derived from fresh bovine dentin
      was evaluated as a co-factor for recombinant human bone morphogenetic protein-2
      (rhBMP-2) in rhBMP-2-induced bone formation in rats. A 5 microg amount of
      Escherichia coli-derived rhBMP-2 variant was combined with DPP cross-linked to
      type I collagen (2.4 microg DPP/360 microg collagen), acting as carrier. Next,
      rhBMP-2/DPP/collagen composites were implanted by onlay-grafting beneath the
      cranial periosteum in 4-week-old Wistar rats. Rats were sacrificed at 2 and 3
      weeks after implantation. Throughout the experimental period, rhBMP
      2/DPP/collagen composite induced more bone formation than the rhBMP-2/collagen
      composite. Moreover, the degradation rate of rhBMP-2/DPP/collagen composite in
      rat was faster than that of rhBMP-2/collagen composite. Neither DPP/collagen
      composite nor collagen alone conducted bone formation even at 3 weeks
      postimplantation. These results indicate that the bone-inducing activity of rhBMP
      2 is enhanced by DPP as a co-factor of rhBMP-2 in vivo.

PMID- 14725819
TI  - Augmentation: understanding a key feature of RLS.

PMID- 14725820
TI  - Trazodone as a hypnotic in major depression.

PMID- 14725821
TI  - Augmentation and tolerance with long-term pramipexole treatment of restless legs
      syndrome (RLS).
AB  - BACKGROUND: Dopaminergic agents have become first-line treatments for restless
      legs syndrome (RLS). The most common serious complications of L-Dopa treatment of
      RLS are "augmentation", in which RLS symptoms appear earlier during the day, and
      tolerance, in which medication effectiveness wanes over time. The aims of this
      study were to assess rates of augmentation and tolerance, and their
      interrelationship, with pramipexole treatment of RLS. PATIENTS AND METHODS:
      Retrospective assessment of all patients (N=59) treated for RLS with pramipexole
      for at least 6 months (mean duration=21.2+/-11.4 months) by the senior author.
      Pramipexole dosing and clinical follow-up were performed in a standardized
      fashion. L-Dopa was discontinued and other medications for RLS were tapered as
      tolerated. Rates of augmentation (need for earlier administration of the same
      dose of pramipexole) and tolerance (need for an increase in pramipexole dose)
      were determined. RESULTS: Augmentation developed in 32% (19/59), and tolerance
      occurred in 46% (27/59), of patients. These two complications were statistically
      related (P<0.05). The only clinical predictors of these complications were
      previous augmentation or tolerance to L-Dopa. CONCLUSIONS: Augmentation and
      tolerance are more common with extended pramipexole treatment of RLS than has
      been previously reported in preliminary studies. However, these complications are
      generally manageable by earlier dosing or small dose increases of this agent, and
      only rarely require medication discontinuation.

PMID- 14725822
TI  - The effects of trazodone on sleep in patients treated with stimulant
      antidepressants.
AB  - BACKGROUND AND PURPOSE: To evaluate the effects of trazodone on subjective and
      objective measures of sleep in depressed insomnia patients treated with selective
      serotonin reuptake inhibitors (SSRIs). SSRIs can exacerbate or cause new insomnia
      while alleviating other symptoms of depression. Trazodone has been reported to be
      an effective hypnotic for patients with antidepressant-associated insomnia.
      PATIENTS AND METHODS: Twelve female patients were given either 100 mg trazodone
      or placebo for 7 days in a double-blind crossover design with a 7-day washout
      period. Polysomnographic recordings were repeated on the 3rd, 9th and 17th, 23rd
      nights after treatment with trazodone or placebo. Sleep was assessed by
      Pittsburgh sleep quality index (PSQI) at the beginning and end of the study.
      Psychological evaluation was done by Hamilton depression rating scale (HDRS).
      RESULTS: Trazodone significantly increased total sleep time, percentage of stages
      3+4, sleep efficiency index, sleep continuity index and decreased percentage of
      stage 1, number of awakenings, stage shifts compared to the baseline. This
      improvement was also obtained after 7 days of treatment. The PSQI score was
      reduced to 5+/-1.6 at the end of the study. HDRS was reduced to 11.5+/-4.5 with
      trazodone and to 12.2+/-3 with placebo. CONCLUSION: Trazodone is effective in the
      treatment of antidepressant-associated insomnia.

PMID- 14725823
TI  - Sleep disorders in multiple system atrophy: a correlative video-polysomnographic
      study.
AB  - OBJECTIVE: The reciprocal relation between breathing, heart and motor system
      abnormalities during sleep was studied in multiple system atrophy (MSA) by means
      of video-polysomnographic recordings (VPSG). PATIENTS AND METHODS: Nineteen
      consecutive MSA patients underwent VPSG with scoring for sleep, respiratory
      abnormalities, heart (HR) and breathing (BR) rates, and abnormal motor
      activities. A comparative analysis was performed versus 10 patients with
      obstructive sleep apnoea syndrome (OSAS). RESULTS: All MSA patients displayed
      snoring, 42% stridor, and 37% OSAS. Mean sleep SaO(2) was 92.7%, and lowest
      SaO(2) 86%. Patients with stridor had a significant increase in BR from Wake to
      NREM and REM sleep, and higher HR during sleep. Respiratory muscles and tibialis
      anterior EMG tonic activity was frequently found, more often in patients with
      stridor. All patients had REM sleep behaviour disorders (RBD) and 88% periodic
      limb movements during sleep (PLMS). No OSAS patient had RBD or respiratory
      muscles and tibialis anterior tonic activity. CONCLUSIONS: MSA patients,
      especially those with associated stridor, commonly display impaired breathing and
      abnormal control of respiratory and limb muscles during sleep. Breathing and
      motor abnormalities are often concomitant in the same patient, indicating a
      diffuse impairment of sleep homeostatic integration that should be included
      within the diagnostic features of MSA.

PMID- 14725824
TI  - Prevalence of excessive daytime sleepiness and associated factors in a Brazilian
      community: the Bambui study.
AB  - BACKGROUND AND PURPOSE: Population-based studies of excessive daytime sleepiness
      (EDS) among adults residing in communities in developing countries are scarce.
      The objectives of the present study were to determine the prevalence of EDS in a
      Brazilian town with 15,000 inhabitants (Bambui, MG), and the socio-demographic
      characteristics associated with it. PATIENTS AND METHODS: In this study, 87.3% of
      1221 randomly selected individuals aged 18+ participated. EDS was defined as the
      presence of sleepiness during the previous month, occurring three or more times
      per week, with consequent impairment of daily activities. RESULTS: EDS was
      reported by 16.8% of the participants. There was no association with age groups
      (P=0.978). Higher prevalence of EDS was seen for women than for men in the
      following age groups: 18-29, 45-59 and 60+. After adjustment for gender, only
      family income was associated with EDS. Complaints of insomnia and the use of
      medicine to improve sleep during the previous month were more frequent among
      individuals with EDS than among those without it. Among those with EDS, 46.3% had
      been symptomatic for more than 1 year; 25 (2.34%) reported use of medication at
      some time in their lives to improve EDS. CONCLUSION: Social differences
      (represented by a lower family income) were an observed factor in the
      distribution of EDS, as were gender and insomnia. The high prevalence of EDS
      indicates that it is an important health problem, even in a small community of a
      developing country.

PMID- 14725825
TI  - Factors associated with a delay in the diagnosis of narcolepsy.
AB  - BACKGROUND: There can be a long interval from the onset of symptoms before a
      diagnosis of narcolepsy is made. There are no multivariate analyses reported in
      the literature of factors that may contribute to this delay. The aims of this
      study were to describe the delay in diagnosis of people with narcolepsy living in
      the UK and to identify associated factors. METHODS: The study comprised a postal
      survey of 500 members of the Narcolepsy Association UK, which included questions
      regarding age of onset of symptoms, year of diagnosis and subject demographics.
      Cox's proportional hazards regression was performed. RESULTS: A total of 313
      questionnaires were returned of which 219 had been completed sufficiently for
      analysis. The interval between symptom onset and diagnosis ranged from within 1
      to 61 years with a median of 10.5 years. Multivariate analysis showed that the
      presence of cataplexy as one of the initial symptoms and a more recent year of
      symptom onset were the only factors associated with time to diagnosis.
      CONCLUSIONS: We have confirmed that the diagnosis of narcolepsy can be delayed
      for many years particularly when cataplexy is absent initially. The delay in
      diagnosis in the UK appears to be decreasing, probably through greater doctor and
      patient awareness of the clinical manifestations of narcolepsy.

PMID- 14725826
TI  - Pregnancy, sleep disordered breathing and treatment with nasal continuous
      positive airway pressure.
AB  - OBJECTIVE: To investigate the tolerance, compliance and problems associated with
      usage of nasal continuous positive airway pressure (CPAP) by pregnant women with
      sleep disordered breathing (SDB). PATIENTS AND METHOD: Twelve pregnant women
      diagnosed with SDB received polysomnography (PSG) at entry, CPAP titration,
      repeat PSG at 6 months gestation (GA) and home monitoring of cardio-respiratory
      variables at 8 months GA. Compliance was verified by the pressure at the mask.
      Results from the Epworth sleepiness scale, fatigue scale and visual analogue
      scales (VAS) for sleepiness, fatigue, and snoring were compared over time.
      RESULTS: All of the subjects had full term pregnancies and healthy infants.
      Nightly compliance was at least 4 h initially and 6.5 h at 6 months GA. Nasal
      CPAP significantly improved all scales compared to entry. VAS scores remained
      lower at 6 months GA compared to entry. Re-adjustment of CPAP pressure was needed
      in six subjects at 6 months GA. CONCLUSION: Nasal CPAP is a safe and effective
      treatment of SDB during pregnancy.

PMID- 14725827
TI  - Associations between chemical odor intolerance and sleep disturbances in
      community-living adults.
AB  - OBJECTIVE: To investigate associations between sleep disturbances and chemical
      odor intolerance (COI), which is the subjective report of feeling ill from common
      odors, such as carpet glue or pesticides. METHODS: This cross-sectional study
      consisted of government employees and their family members (n=140; 61% women,
      mean age=46.3 years) derived from a stratified cluster population living in Pima
      County, Tucson, AZ. Subjects completed a standard survey that included sleep
      symptoms, a validated measure of COI, and two questions regarding anxiety and
      depression. Odds ratios (OR) with 95% confidence intervals (CI) were computed to
      test the association between COI and sleep symptoms. Stratification according to
      the Mantel-Haenszel method and logistic regression models were used to test for
      confounding and/or effect modification. RESULTS: After adjusting for age and
      gender, subjects with COI were significantly more likely to report difficulty
      staying asleep (OR=3.06; CI=1.17-8.03), insufficient sleep (OR=3.93; CI=1.43
      10.79), and nightmares (OR=3.17; CI=1.14-8.81) compared to persons without COI.
      Associations between COI, sleep maintenance problems and insufficient sleep were
      still significant after adjusting for gender and depression; however, the
      association between COI and nightmares became borderline. CONCLUSIONS: Compared
      to the non-COI, persons with COI are more likely to report sleep maintenance
      insomnia and insufficient sleep independent of self-reported depression.
      Nightmares appear to be related more to depression than to COI.

PMID- 14725828
TI  - Annual review of patients with sleep apnea/hypopnea syndrome--a pragmatic
      randomised trial of nurse home visit versus consultant clinic review.
AB  - BACKGROUND: This pragmatic randomised, controlled trial investigated annual
      review of patients with sleep apnea/hypopnea syndrome (SAHS). Clinical outcomes
      and costs were compared for consultant clinic review versus specialist nurse home
      visit. METHOD: One hundred and seventy-four patients were randomised to annual
      review by consultant clinic appointment or by specialist nurse home visit. SAHS
      symptoms, Epworth score, hospital anxiety and depression scale (HADS), Short Form
      36 (SF-36) and hours of use of constant positive airway pressure (CPAP) were
      measured before and 3 months after review. The costs and patient preference for
      review were determined. RESULTS: After review, both groups significantly
      increased CPAP use (mean (SD) increase: nurse, 0.66 (1.71) h; consultant, 0.45
      (1.69) h) and reduced symptom scores (nurse, -2 (7); consultant, -3 (9)),
      compared to baseline. There were no differences between groups in these
      improvements, or in HADS or SF-36 scores. Average duration of a nurse home visit,
      excluding travel time, was 26 (6) min. Total NHS cost per visit was 52.26 UK
      pounds (49.85) ($83.62 (79.76)), of which 6.57 UK pounds (1.43) ($10.51 (2.29))
      reflected time spent with the patient and the remainder was travel cost. Average
      duration of consultant review was 10 (6) min, total NHS cost 6.21 UK pounds
      (3.99) ($9.94 (6.38)). However, the cost to the patient of attending the clinic
      was 23.63 UK pounds (23.21) ($37.81 (37.13)). Patient preference for review was
      nurse 16%, consultant 19%, and no preference 65%. CONCLUSION: Following annual
      review, use of CPAP increased and symptoms improved. Outcomes were similar for
      consultant and nurse led review. Home visits were expensive for the healthcare
      provider, whereas clinic attendance incurred substantial costs to the patient.
      The majority of patients would accept nurse review for their sleep apnea
      management.

PMID- 14725829
TI  - Studio Morfeo: insomnia in primary care, a survey conducted on the Italian
      population.
AB  - BACKGROUND AND PURPOSE: To carry out an observational epidemiological survey
      (Studio Morfeo), to determine: (1) the frequency of insomnia in a large Italian
      population presenting directly to the general physician (GP); (2) the impact of
      insomnia on the quality of life, on the use of health-care resources and on co
      morbidity. PATIENTS AND METHODS: The study was accomplished by GPs, trained by
      sleep specialists accredited by the Italian Association of Sleep Medicine. Only
      patients spontaneously presenting to their GP for medical problems were surveyed.
      Each GP was asked to enroll at least five patients across a routine week of
      medical activity including both morning and afternoon clinics. The first patient
      of each weekday was recruited after obtaining written consent. According to the
      responses to the sleep-related questions, patients were classified into three
      categories: (1) no insomnia, (2) level 1 insomnia with absence of day-time
      dysfunction and (3) level 2 insomnia with presence of day-time dysfunction.
      RESULTS: A total of 3284 patients were enrolled by 738 GPs in this Italian
      survey. Insomnia was reported by 64% of all interviewed patients, with 20%
      classified as level 1 and 44% as level 2. Logistic analysis indicated that
      depression (odds ratio, 2.70), involvement of >1 organ systems (odds ratio,
      1.24), female gender (odds ratio, 1.19), unemployment (odds ratio, 1.18), low
      education (odds ratio, 1.18) and increasing age (odds ratio, 1.02) were the major
      risk factors for insomnia. CONCLUSIONS: Our findings indicate that insomnia is a
      frequent disturbance in the Italian primary care population, is associated with
      high risk of co-morbid conditions, and results in increased use of health-care
      resources.

PMID- 14725830
TI  - Subclinical rhythmic electrographic discharge of adults (SREDA) in REM sleep.
AB  - We describe the first reported case of subclinical rhythmic electrographic
      discharge of adults (SREDA) during rapid eye movement (REM) sleep. This 48-year
      old man, with a history of witnessed apneic spells, was sent for a baseline
      polysomnogram. Besides demonstrating obstructive sleep apnea, his study showed
      the occurrence of paroxysmal delta waves evolving into a theta frequency during
      REM sleep. A repeat polysomnogram with 16-channel electroencephalography
      confirmed SREDA in the bilateral temporal/parietal regions during REM sleep. This
      uncommon paroxysmal electrographic pattern should not be mistaken for seizure
      activity and is now recognized to occur in all stages of sleep, including REM.

PMID- 14725833
TI  - Iron status and periodic limb movements of sleep in children: a causal
      relationship?

PMID- 14725834
TI  - Hypocretine system deficiency in Parkinson's disease.

PMID- 14725835
TI  - Association between polymorphism within the promoter region of the serotonin
      transporter gene and treatment response in depression-further evidence but still
      controversial issues.

PMID- 14725836
TI  - Sleep and sleep disorders in Don Quixote.
AB  - In Don Quijote de la Mancha, Miguel de Cervantes presents Don Quixote as an
      amazing character of the 17th century who suffers from delusions and illusions,
      believing himself to be a medieval knight errant. Besides this neuropsychiatric
      condition, Cervantes included masterful descriptions of several sleep disorders
      such as insomnia, sleep deprivation, disruptive loud snoring and rapid eye
      movement sleep behaviour disorder. In addition, he described the occurrence of
      physiological, vivid dreams and habitual, post-prandial sleepiness--the siesta.
      Cervantes' concept of sleep as a passive state where all cerebral activities are
      almost absent is in conflict with his description of abnormal behaviours during
      sleep and vivid, fantastic dreams. His concept of sleep was shared by his
      contemporary, Shakespeare, and could have been influenced by the reading of the
      classical Spanish book of psychiatry Examen de Ingenios (1575).

PMID- 14725840
TI  - The neuropsychology of epilepsy: what are the factors involved?

PMID- 14725841
TI  - Behavioral aspects of pediatric epilepsy syndromes.
AB  - Apart from control of the seizures, two of the most important factors in
      determining how well a child with epilepsy progresses toward independence are
      cognition and behavior. The diagnosis of the correct epilepsy syndrome often
      provides information with regard to probability of good seizure control and
      intellectual outcome. However, relatively little has been published on the
      behavioral aspects of the various epilepsy syndromes. In West syndrome there is
      emerging evidence that early effective treatment might improve outcome in terms
      of both cognition and behavior. The work on this syndrome in children with
      tuberous sclerosis has demonstrated an association between temporal lobe tubers
      and autism. In Dravet syndrome, a variety of psychiatric disorders have been
      reported, including hyperactivity and autistic features. This is another epilepsy
      syndrome that tends to be resistant to treatment, implying that the prognosis has
      to be guarded. The behavioral problems reported with Lennox-Gastaut syndrome also
      include autistic features, as well as generally sluggish behavior. It is very
      likely that these characteristics largely reflect the effect of ongoing seizure
      activity. Autistic features, aggression, and hyperkinesis have been described
      with Landau-Kleffner syndrome. The behavior may improve dramatically with
      appropriate medical treatment or after multiple subpial transection. Although the
      syndrome of benign partial seizures with centrotemporal or rolandic spikes is
      said to have a very good prognosis, it is becoming increasingly evident that
      behavioral problems such as concentration difficulties, tempers, hyperactivity,
      and impulsivity might occur. Juvenile myoclonic epilepsy has been associated with
      very variable behavioral traits, sometimes with immature personality features and
      poor social adjustment suggesting frontal lobe dysfunction. Because many of the
      reports of behavioral disturbance associated with epilepsy syndromes are
      anecdotal and do not include validated measures of behavior it would be unwise to
      draw firm conclusions from them at this stage. Carefully conducted prospective
      studies, paying particular attention to any behavioral improvements that occur
      with successful treatment of the epilepsy, are required.

PMID- 14725842
TI  - Neuropsychological aspects of type of epilepsy and etiological factors in adults.
AB  - Whether certain types of epilepsies and etiologies are related to profiles of
      cognitive impairment is of interest for diagnostics and treatment. The dichotomy
      between generalized and focal epilepsies (mesial temporal lobe, frontal lobe,
      parietal, and occipital lobe epilepsies) is considered. Then the most frequent
      etiologies are discussed. We conclude that specific associations between
      neuropsychological deficits and type of epilepsy and etiology are rather
      exceptions. However, knowledge of the type of epilepsy and pathology provides
      eminent information to evaluate the nature of deficits, to estimate chances of
      functional recovery, to provide rehabilitation recommendations, and to support
      decisions about treatment options.

PMID- 14725843
TI  - Neuropsychological effects of seizures.
AB  - The neuropsychological effects of seizures, including an accumulation of single
      attacks, on mental abilities are explored through a selective review of the
      world's literature. Each paper included in this review was longitudinal in
      nature, and in each case, formal psychological testing was accomplished both at
      the beginning and at the end of the study. Of the 22 investigations meeting all
      requirements for inclusion, 9 focused on children and 13 on adolescents and
      adults. Some difficulties were encountered in that the types and numbers of
      seizures occurring during the studies were rarely included. Except in three
      studies where there were very few seizures of any kind, it appears justifiable to
      assume that the patients in all other studies had active seizure disorders.
      Assuming this to be true, in 12 of the remaining 20 papers, a relationship was
      found between seizures and changes in mental abilities, in 5 cases the results
      were mixed or uncertain, and in 3 cases the available evidence was against such a
      relationship. Mild but definite relationships between seizures and mental decline
      are supported by this literature review, but these relationships require much
      more study, particularly with a clearer understanding of the types and
      frequencies of seizures experienced. Suggestions for future research are offered.

PMID- 14725844
TI  - Effects of epileptiform EEG discharges on cognitive function: is the concept of
      "transient cognitive impairment" still valid?
AB  - In this article we review the existing evidence on the cognitive impact of
      interictal epileptiform EEG discharges. Such cognitive impairment occurs
      exclusively in direct relation to episodes of epileptiform EEG discharges and
      must be distinguished from (post) ictal seizure effects and from the nonperiodic
      long-term "stable" interictal effects caused by the clinical syndrome or the
      underlying etiology. Especially in patients with short nonconvulsive seizures,
      characterized often by difficult-to-detect symptoms, the ictal or postictal
      effects may be overlooked and the resulting cognitive effects may be erroneously
      related to the epileptiform EEG discharges. The existing epidemiological data
      show that the prevalence of cognitive impairment during epileptiform EEG
      discharges is low. In one study 2.2% of the patients referred to a specialized
      epilepsy center for EEG recording showed a definite relationship between
      epileptiform EEG discharges and cognitive impairments ("transient cognitive
      impairment"). Several studies have sought to analyze to what extent cognitive
      impairment can be attributed to epileptiform EEG discharges among the other
      epilepsy factors (such as the effect of the clinical syndrome). These studies
      show that epileptiform EEG discharges have an additional and independent effect,
      but this effect is mild and limited to transient mechanistic cognitive processes
      (alertness, mental speed). This finding concurs with clinical studies that also
      reported only mild effects. In only exceptional cases are epileptiform EEG
      discharges the dominant factor explaining cognitive impairment. In addition, some
      studies have indicated that such mild effects may accumulate over time (when
      frequent epileptiform EEG discharges persist over years) and consequently result
      in effects on stable aspects of cognitive function such as educational
      achievement and intelligence. Hence, the clinical relevance is that early
      detection of cognitive effects of epileptiform EEG discharges and subsequent
      treatment may prevent a definite impact on cognitive and educational development.
      The disruptive effects of epileptiform EEG discharges on long-term potentiation,
      as established in animal experiments, may be one of the neurophysiological
      mechanisms underlying this accumulation. In conclusion the concept of "transient
      cognitive impairment" is still valid, but refinement of methodology has shown
      that a large proportion of presumed transient cognitive impairment can be
      attributed to subtle seizures, while interictal epileptic activity accounts for a
      much smaller part of the cognitive effects than previously thought. In particular
      cryptogenic partial epilepsies are associated with the risk of cognitive
      impairment. We hope that increased clinical awareness of this need for early
      detection will stimulate longitudinal and prospective research that eventually
      also will provide an answer to the questions of when and how epileptiform
      discharges that are not part of a seizure need to be treated.

PMID- 14725845
TI  - Do seizures cause irreversible cognitive damage? Evidence from animal studies.
AB  - Data from experimental models provide evidence that both prolonged and brief
      seizures can cause irreversible impairment in spatial and emotional learning and
      memory. Factors related to the severity of the behavioral impairments include
      genetic background, age at the time of the epileptogenic insult, extent of brain
      lesion, location of seizure focus, seizure duration, seizure number, brain
      reserve, and environmental and social living conditions. Further, as in humans,
      the interval between the last seizure and behavioral testing as well as treatment
      with antiepileptic drugs can affect the test results.

PMID- 14725846
TI  - Neuropsychological aspects of epilepsy surgery.
AB  - Neuropsychological evaluation of a patient's cognitive capabilities before and
      after epilepsy surgery is essential in elective epilepsy surgery. On the one
      hand, neuropsychology provides accessory information regarding the localization
      and lateralization of epilepsy-associated cognitive impairment; on the other
      hand, it is a useful tool for quality and outcome control of epilepsy surgery
      which helps to make surgery more effective and safe. Evaluation of the adequacy
      of the brain tissues to be resected and of the patient's mental reserve
      capacities allows for a prediction of the postoperative cognitive development.
      Successful surgery can stop mental decline due to chronic epilepsy and it can
      reverse this negative trend by release of functions and capacities that were
      secondarily affected before surgery. However, surgery bears the risk of
      additional impairments which, in interaction with normal or even pathological
      processes of mental aging, may accelerate cognitive decline at an older age. From
      a neuropsychological point of view, early recognition of pharmacoresistance is
      important along with early and complete seizure control with maximal sparing of
      functional tissues.

PMID- 14725847
TI  - Vagus nerve stimulation: mood and cognitive effects.
AB  - Many antiepileptic medications modulate affective and cognitive functions. In
      keeping with these observations, a growing body of literature suggests that vagus
      nerve stimulation (VNS) may have similar effects. This review evaluates the
      published evidence for VNS-associated changes in mood and cognition in patients
      with neuropsychiatric disorders.

PMID- 14725848
TI  - Cognitive side effects of antiepileptic drugs.
AB  - Antiepileptic drugs produce global changes in the excitation levels in the
      central nervous system and often lead to cognitive and behavioral deficits. These
      deficits vary and must be considered independently in every patient. A number of
      consistent risk factors have been established. Polypharmacy and high blood levels
      of an antiepileptic drug (AED) increase the risk of cognitive side effects.
      Different effects have been demonstrated for some AEDs, but comparative data are
      incomplete across all of them. Other factors such as patient age and
      type/frequency of seizures may also be important contributors to the patient's
      cognitive state. AEDs can have positive or negative effects on mood, providing
      another consideration in choosing the course of treatment.

PMID- 14725849
TI  - Mood effects of antiepileptic drugs.
AB  - This article reviews our knowledge about a specific subgroup of chronic CNS
      related side effects of antiepileptic drugs (AED) treatment, i.e., the effects of
      AEDs on mood. In line with a recent hypothesis, using the experience of AED
      treatment in psychiatry, we examined whether mood effects are related to the
      known anticonvulsant mechanisms of action of the AEDs. Specifically we examined
      whether AEDs, acting through potentiation of GABAergic neurotransmitter release,
      have "sedating" effects on mood, whereas AEDs that act through the reduction of
      excitatory glutamate neurotransmitter release have "activating" effects on mood.
      The results of this review yield evidence that there are relationships between
      the known anticonvulsant mechanisms of action of the AEDs and mood effects. Mood
      effects occur especially when the drugs have a sustained effect on neuronal
      mechanisms, in particular when the inhibitory or excitatory neurotransmitter
      release is altered. Drugs with "use-dependent" impact on sodium or calcium
      channels probably have a more transient impact and do not lead to interictal
      stable mood effects. Drugs with multiple mechanisms of action seem to combine a
      favorable efficacy profile with an increased risk of severe mood problems. The
      quality of the evidence, however, is not conclusive and there are many
      paradoxical results. One reason for this lack of "fit" may be the use in this
      review of a simplified classification, based only on the predominant mechanism of
      action to classify a drug. Only a limited number of AEDs (ethosuximide,
      tiagabine) are characterized by a single anticonvulsant mechanism of action.
      Probably more detailed coupling of mechanisms of action (e.g., inspecting the
      type and route of impact on GABA release) and mood effects may give less
      confusing results. The use of magnetic resonance imaging techniques such as
      spectroscopy may provide interesting results.

PMID- 14725850
TI  - The dos and don'ts of neuropsychological assessment in epilepsy.
AB  - Neuropsychologists have a significant role in the assessment, treatment, and
      rehabilitation of people with epilepsy. This includes providing an assessment of
      an individual's cognitive strengths and weaknesses with respect to being a
      candidate for the surgery program, detailing intellectual and memory impairments
      as part of a rehabilitation service, and documenting specific antiepileptic drug
      effects as part of routine clinical management. Each of these specific roles
      requires careful consideration with respect to the potential pitfalls they can
      present to the neuropsychologist. In this article, we have attempted to identify
      the most obvious "dos and don'ts" in the neuropsychological assessment of people
      with epilepsy. These range from issues relating to the reliance of measures, to
      the failure to document patients' backgrounds, to the importance of considering
      the psychometric tests that we use. We have attempted to emphasize the importance
      or value of a well-conducted neuropsychological assessment to the management of
      the person with epilepsy.

PMID- 14725851
TI  - Lessons for neuropsychology from functional MRI in patients with epilepsy.
AB  - This contribution aims to review the major findings of pre- and postsurgical
      functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy
      from a neuropsychological perspective. We compared the contribution of fMRI with
      the intracarotid amytal procedure (IAP) with respect to functional mapping of
      language and memory in patients with therapy-resistant epilepsy. We conclude that
      using comprehensive language paradigms, fMRI has been able (1) to provide
      estimates of the degree of language lateralization including the degree of
      involvement of the nondominant hemisphere, (2) to provide information on the
      location of its activated network during expressive and receptive language, and
      (3) to help delineate eloquent language regions in the vicinity of the surgical
      target, thus preventing postoperative complications. The contribution of the
      frequently observed nondominant hemisphere activation to language should be
      explored and its clinical relevance determined. Evidence from fMRI studies is
      accumulating that reorganization of cognitive and motor function favors the
      activation of contralateral homotopic areas, although this process is far from
      understood. The exact functional contribution of atypical areas of activation
      should be investigated critically. In the presurgical evaluation process,
      detailed and reliable localization of language and memory functions of the
      individual patient is mandatory and should be the ultimate goal in the
      development of comprehensive clinical fMRI protocols.

PMID- 14725852
TI  - Antioxidant defense system in the apple snail eggs, the role of ovorubin.
AB  - A novel role of ovorubin as a protection system against oxidative damage in eggs
      from Pomacea canaliculata was investigated. Carotenoid composition, and their
      antioxidant capacity, as well as the carotenoid-apoprotein interaction, were
      studied for this lipoglycocarotenoprotein. Carotenoid extracts from ovorubin were
      analysed by TLC and spectrophotometry. The major carotenoid was astaxanthin in
      its free (40%), monoester (24%), and diester (35%) forms, mainly esterified with
      16:0 fatty acid. The antioxidant capacity of ovorubin carotenoids was studied by
      the inhibition of microsomal oxidation in a non-enzymatic system, showing strong
      protection against oxidative damage (IC50=3.9 nmol/mg protein). The carotenoid
      apoprotein interaction was studied by spectrophotometry and electrophoresis using
      reconstituted ovorubin. Astaxanthin does not seem to affect the structural
      characteristics of ovorubin, however the carotenoid-protein association
      significantly protected astaxanthin against oxidation. Ovorubin therefore,
      besides its role in providing energy and structural precursors during
      embryogenesis, would be an antioxidant carrier, protecting at the same time this
      pigment from oxidation in the perivitellin fluid environment of the egg.

PMID- 14725853
TI  - Subsite specificities of granzyme M: a study of inhibitors and newly synthesized
      thiobenzyl ester substrates.
AB  - Granzyme M is a member of a family of granule serine proteases that participate
      in target cell death initiated by cytotoxic lymphocytes. The enzyme is almost
      exclusively expressed in NK cell types. Granzyme M cleaves at the carboxy side of
      amino acids with long, hydrophobic side chains like Met, Leu, and Nle. To further
      study the substrate specificity of the enzyme, a series of peptide thiobenzyl
      esters was synthesized. The hydrolysis of the substrates with murine and human
      recombinant forms of granzyme M was observed. The results show that the enzyme
      has a strong preference for Pro at the P2 position and Ala, Ser, or Asp at the P3
      position. These results suggest that the protein residues of the S2 and S3
      subsites form important binding interactions that aid in the selection of
      specific natural substrates for granzyme M. A series of inhibitors was also
      tested with granzyme M. None of the inhibitors were effective inactivators of
      granzyme M, including the general serine protease inhibitor, 3,4
      dichloroisocoumarin, which is usually a potent inactivator of serine proteases.
      This suggests that inhibition of granzyme M may be difficult. Also reported for
      the first time is the method utilized to isolate granzyme M used in this and
      previous publications. The observations in this paper will be valuable in
      development of new potent inhibitors for granzyme M as well as assist in
      determining the biological function of the enzyme.

PMID- 14725854
TI  - Functional characterization of four allelic variants of human cytochrome P450
      1A2.
AB  - Human cytochrome P450 1A2 catalyzes important reactions in xenobiotic metabolism,
      including the N-hydroxylation of carcinogenic aromatic amines. In 2001, Chevalier
      et al. reported four new P450 1A2 sequence variants in the human population. We
      have now expressed these variants in Escherichia coli and measured protein
      expression (optical spectroscopy of holoenzyme and immunoblotting) and
      bioactivation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and MeIQ (2-amino
      2,4-dimethylimidazo[4,5-f]quinoline) in the lacZ reversion mutagenicity test.
      Enzyme kinetic analyses were performed for N-hydroxylation of five heterocyclic
      amine substrates and for O-deethylation of phenacetin. The most drastic effect
      was that of the R431W substitution: no holoenzyme was detectable. This residue is
      located in the "meander" peptide region and earlier site-directed mutagenesis
      studies demonstrated that it is critical for maintenance of protein tertiary
      structure. The other three variants had subtly different catalytic activities
      compared to the wild-type enzyme.

PMID- 14725855
TI  - Identification of variable amino acids in the SRS1 region of CYP6B1 modulating
      furanocoumarin metabolism.
AB  - The homology model of Papilio polyxenes CYP6B1 places Ile115, one of two variable
      amino acids, in the SRS1 of various CYP6B subfamily proteins in close proximity
      to the heme and Ala113, another variable amino acid, in a more distal position.
      We have constructed mutant CYP6B1 proteins altered at either of these positions
      and homology models of each based on multiple alignments with crystallized P450
      proteins. The homology models suggest the existence of significant structural
      diversity in the hydrogen bond network surrounding the heme as a result of single
      point mutations in SRS1. Mutagenesis of Ile115 or Ala113 to other residues
      present in the insect CYP6B subfamily indicates that these amino acids control
      the spin state of the heme and, as a result, the catalytic activity of this
      monooxygenase. In particular, the I115L mutation significantly increases the spin
      state of the heme coordinately with 2- to 4-fold increases in its turnover of
      linear furanocoumarins. Other A113V, A113L, A113Q, and A113E mutations display
      more variation in their effects but, in each case, strong correlations exist
      between furanocoumarin turnover and heme spin state. These data demonstrate that
      variable amino acids in SRS1 of the insect CYP6B subfamily exert dramatic effects
      on the range of furanocoumarins metabolized, even when they occur in positions
      potentially distal from the substrate. These effects are possibly mediated
      through rearrangement of the local hydrogen bond network.

PMID- 14725856
TI  - Aryl hydrocarbon receptor-mediated posttranscriptional regulation of IL-1beta.
AB  - TCDD stimulated IL-1beta gene expression in differentiating human keratinocyte
      cell lines in a time- and dose-dependent manner. Increases in prointerleukin
      1beta (pIL-1beta) protein and IL-1beta steady state mRNA levels were observed in
      both SCC-12F and HaCaT cells following TCDD treatment. When pretreated with alpha
      naphthoflavone, an AhR antagonist, TCDD-mediated increases in IL-1beta gene
      expression were attenuated, demonstrating for the first time that the
      environmental toxin, TCDD, can stimulate cytokine (IL-1beta) gene expression in
      an AhR-dependent manner. Nuclear run-on experiments were performed in SCC-12
      cells to determine if the AhR-dependent increases in IL-1beta expression were due
      to transcriptional activation of the IL-1beta gene. Results showed high
      constitutive levels of IL-1beta transcriptional activity, however, TCDD
      treatment, which stimulated IL-1beta steady state mRNA levels, failed to
      potentiate IL-1beta transcription. Taken together, these results demonstrate that
      AhR-mediated IL-1beta regulation is occurring posttranscriptionally.

PMID- 14725857
TI  - Heteromeric geranyl diphosphate synthase from mint: construction of a functional
      fusion protein and inhibition by bisphosphonate substrate analogs.
AB  - Geranyl diphosphate synthase catalyzes the condensation of dimethylallyl
      diphosphate (C(5)) with isopentenyl diphosphate (C(5)) to produce geranyl
      diphosphate (C(10)), the essential precursor of monoterpenes. The enzyme from
      peppermint and spearmint (Menthaxpiperita and Mentha spicata, respectively)
      functions as a heterodimer or heterotetramer consisting of a 40kDa subunit and
      33kDa subunit. The DNAs encoding each subunit were joined with different sized
      linkers and in both possible orders, and expressed in Escherichia coli to yield
      the corresponding fused protein. The properties of the recombinant fused version,
      in which the small subunit was followed by the large subunit with a 10 amino acid
      linker, resembled those of the native heteromeric enzyme in kinetics, product
      chain-length specificity, and architecture, and this form thus provided a
      suitable single gene transcript for biotechnological purposes. Bisphosphonate
      substrate analogs of the type that inhibit farnesyl diphosphate synthase (C(15))
      and geranylgeranyl diphosphate synthase (C(20)) also inhibited the fused geranyl
      diphosphate synthase, apparently by interacting at both the allylic and
      homoallylic co-substrate binding sites. The results of inhibition studies, along
      with the previously established role of the small subunit and related mutagenesis
      experiments, suggest that geranyl diphosphate synthase employs a different
      mechanism for chain-length determination than do other short-chain
      prenyltransferases.

PMID- 14725858
TI  - Osmotic response in Lactobacillus casei ATCC 393: biochemical and biophysical
      characteristics of membrane.
AB  - The biochemical and biophysical properties of the membrane and some general
      characteristics of the response of Lactobacillus casei ATCC 393 (reclassified
      Lactobacillus zeae) to hyperosmotic conditions were studied. Under hypertonic
      conditions, the hydrophobicity and the bile salt sensitivity of the cultures were
      increased. The glycolipid AcylH3DG is only present in membranes of NaCl
      containing medium, whereas, H4DG undergoes a significant increment and H2DG a
      significant decrease. The fluidity of both the purified membranes and the total
      lipid vesicles, as determined with the fluorescent probe DPH, did not change in
      conditions of high salinity. This was coincident with changes in the fatty acid
      (FA) composition where an increase in the saturated/unsaturated FA ratio was
      compensated by a rise in the fluidifying 11,12-methyleneoctadecanoic FA (cyc
      19:0). Under osmotic stress conditions, Laurdan and acridine orange in total
      lipid vesicles showed increased lateral lipid packing and proton permeability,
      respectively.

PMID- 14725859
TI  - Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives:
      cloning and characterization of a C4H from a psoralen producing plant-Ruta
      graveolens-exhibiting low sensitivity to psoralen inactivation.
AB  - Cinnamate 4-hydroxylase (C4H, EC 1.14.13.11) complete cDNA was cloned from the
      leaves of Ruta graveolens, a psoralen producing plant. The recombinant enzyme
      (classified CYP73A32) was expressed in Saccharomyces cerevisiae. Mechanism-based
      inactivation was investigated using various psoralen derivatives. Only psoralen
      and 8-methoxypsoralen were found to inactivate C4H. The inactivation was
      dependent on the presence of NADPH, time of pre-incubation, and inhibitor
      concentration. Inactivation stoichiometry was 0.9 (+/-0.2) for CYP73A1 and 1.1
      (+/-0.2) for CYP73A32. SDS-PAGE analysis demonstrated that [3H]psoralen was
      irreversibly bound to the C4H apoprotein. K(i) and k(inact) for psoralen and 8
      methoxypsoralen inactivation on the two C4H revealed a lower sensitivity for
      CYP73A32 compared to CYP73A1. Inactivation kinetics were also determined for
      CYP73A10, a C4H from another furocoumarin-producing plant, Petroselinum crispum.
      This enzyme was found to behave like CYP73A32, with a weak sensitivity to
      psoralen and 8-MOP inactivation. Cinnamic acid hydroxylation is a key step in the
      biosynthesis of phenylpropanoid compounds, psoralen derivatives included. Our
      results suggest a possible evolution of R. graveolens and P. crispum C4H that
      might tolerate substantial levels of psoralen derivatives in the cytoplasmic
      compartment without a depletive effect on C4H and the general phenylpropanoid
      metabolism.

PMID- 14725860
TI  - The rat enhancer of split- and hairy-related protein-2 gene: hepatic expression,
      genomic structure, and promoter analysis.
AB  - The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is a basic helix
      loop-helix transcription factor. The hepatic expression of SHARP-2 mRNA was
      investigated under various conditions. The level was decreased in the
      regenerating rat liver and malignant hepatoma cells. In contrast, the expression
      of SHARP-2 mRNA was induced in rat livers by feeding a high-carbohydrate diet. To
      analyze the molecular mechanism involved in the regulation of the rat SHARP-2
      gene expression, the gene was cloned. It was approximately 6-kb in length and
      consists of five exons and four introns. To investigate the transcriptional
      regulatory region of this gene, SHARP-2/firefly luciferase reporter plasmids were
      transfected into hepatoma cells. A functional analysis of 5(')-deletion
      constructs revealed that two E box sequences between -160 and -144 are mainly
      responsible for promoter activity. Although upstream stimulatory factors (USFs)
      bound to the element in vitro, USF2 failed to stimulate promoter activity from
      the element using the co-transfection experiment. Therefore, other E box-binding
      transcription factors differing from USF proteins or USF-associated proteins are
      necessary for transcriptional stimulation of the rat SHARP-2 gene.

PMID- 14725861
TI  - Anthocyanidin reductases from Medicago truncatula and Arabidopsis thaliana.
AB  - Anthocyanidin reductase (ANR), encoded by the BANYULS gene, is a newly discovered
      enzyme of the flavonoid pathway involved in the biosynthesis of condensed
      tannins. ANR functions immediately downstream of anthocyanidin synthase to
      convert anthocyanidins into the corresponding 2,3-cis-flavan-3-ols. We report the
      biochemical properties of ANRs from the model legume Medicago truncatula (MtANR)
      and the model crucifer Arabidopsis thaliana (AtANR). Both enzymes have high
      temperature optima. MtANR uses both NADPH and NADH as reductant with slight
      preference for NADPH over NADH. In contrast, AtANR only uses NADPH and exhibits
      positive cooperativity for the co-substrate. MtANR shows preference for potential
      anthocyanidin substrates in the order cyanidin>pelargonidin>delphinidin, with
      typical Michaelis-Menten kinetics for each substrate. In contrast, AtANR exhibits
      the reverse preference, with substrate inhibition at high concentrations of
      cyanidin and pelargonidin. (+)-Catechin and (+/-)-dihydroquercetin inhibit AtANR
      but not MtANR, whereas quercetin inhibits both enzymes. Possible catalytic
      reaction sequences for ANRs are discussed.

PMID- 14725862
TI  - Achacin induces cell death in HeLa cells through two different mechanisms.
AB  - Achacin, which belongs to the L-amino acid oxidase group, oxidizes free amino
      acids and produces hydrogen peroxide in cell culture systems. Morphological
      changes in cells incubated with achacin were similar to those of cells incubated
      with H(2)O(2). In both cases, the end result was cell death. To examine the
      mechanism of achacin-associated cytotoxicity, the H(2)O(2) scavenger catalase was
      added to culture media. Features typical of apoptosis, including morphological
      changes, DNA fragmentation, and PARP cleavage, were observed when cells were
      incubated with achacin in the presence of catalase. Moreover, apoptosis was
      inhibited by Z-VAD-fmk, a broad-spectrum caspase inhibitor. Herein, we present
      evidence that two pathways are involved in achacin-induced cell death. One is
      direct generation of H(2)O(2) through the L-amino acid oxidase activity of
      achacin. The other is the caspase-mediated apoptotic pathway that is induced by
      depletion of L-amino acids by achacin.

PMID- 14725863
TI  - Characterization of botryococcene synthase enzyme activity, a squalene synthase
      like activity from the green microalga Botryococcus braunii, Race B.
AB  - The extracellular matrix of the alga Botryococcus braunii, Race B, consists
      mainly of botryococcenes, which have potential as a hydrocarbon fuel.
      Botryococcenes are structurally similar to squalene raising the possibility of a
      common enzyme for the biosynthesis of both. While B. braunii squalene synthase
      (SS) enzyme activity has been documented, botryococcene synthase (BS) enzyme
      activity has not been. In the current study, an assay for BS activity has been
      developed and used to show that many of the assay conditions for BS enzyme
      activity are similar to those of SS. However, SS enzyme activity is stimulated by
      Tween 80 while BS enzyme activity is inhibited. Moreover, BS enzyme activity was
      correlated with the accumulation of botryococcenes during a B. braunii culture
      growth cycle, which was distinctly different from the profile of SS enzyme
      activity. While the current results indicate a conservation of enzymological
      features amongst the BS and SS enzymes, raising the possibility of one enzyme
      capable of catalyzing both activities, they are also consistent with these two
      activities arising from separate and distinct enzymes.

PMID- 14725864
TI  - Anxiety and substance use disorders: introduction to the special series.
AB  - The interplay between anxiety pathology and substance use disorders is
      increasingly recognized in empirical and clinical work. The present article
      serves as a general introduction to the special series highlighting the
      relationship between a number of anxiety conditions and a variety of substance
      use disorders. In this overview, we first discuss the importance of better
      understanding the association between anxiety and substance use and abuse
      followed by a brief review of each study and their major findings. This set of
      studies has implications for our understanding of the nature of these conditions
      as well as their treatment. We hope that this body of work will inspire future
      research in this important area.

PMID- 14725865
TI  - Smoking behaviors across anxiety disorders.
AB  - The purpose of this study was to test the theory put forth by Zvolensky et al.
      [Clin. Psychol. Sci. Pract. 10 (2003) 29] that smoking is specifically associated
      with panic disorder (PD) and not more generally associated with other anxiety
      disorders. Smoking behaviors were examined across three anxiety disorders: panic
      disorder with or without agoraphobia, social phobia (SP), and obsessive
      compulsive disorder (OCD). A greater proportion of the PD group (40.4%) reported
      smoking compared to the SP (20%) and OCD (22.4%) groups. Those in the PD group
      were also more likely than those in the other groups to report being a heavy
      smoker (greater than 10 cigarettes daily). No significant interaction between
      diagnosis and smoking status was found for any of the symptom measures. However,
      participants who smoked had significantly higher scores than nonsmokers on a
      number of scales, including measures of depression, general anxiety, and
      distress. Differences in anxiety sensitivity between smokers and nonsmokers
      approached significance. These findings provide support for Zvolensky et al.'s
      [Clin. Psychol. Sci. Pract. 10 (2003) 29] theoretical conceptualization and
      suggest a specific link between smoking and panic disorder. Further investigation
      is warranted to determine the causal direction of this association.

PMID- 14725866
TI  - Emotional responding to biological challenge as a function of panic disorder and
      smoking.
AB  - The present investigation evaluated anxious and fearful responding to bodily
      sensations as a function of panic disorder (PD) and smoking status. Participants
      completed a voluntary hyperventilation procedure that elicits panic-relevant
      bodily sensations. Psychophysiological data were collected throughout the study
      procedures. Assessments of anxiety and bodily distress were conducted pre
      challenge baseline, post-hyperventilation, and during a recovery period following
      the challenge. Results indicated that smokers with PD reported greater levels of
      anxiety and bodily distress than smokers without PD and than nonsmokers with PD
      at the post-challenge assessment and recovery period. No differences in autonomic
      responding were evident during the challenge or in the recovery phase. In terms
      of rate of recovery, the linear decrease in anxiety, but not bodily distress, was
      significantly more steep for nonsmokers with PD than for smokers with PD. These
      findings are discussed in relation to better understanding the potential role
      that smoking may play in terms of anxious and fearful responding to bodily
      sensations.

PMID- 14725867
TI  - Social anxiety and alcohol use: evaluation of the moderating and mediating
      effects of alcohol expectancies.
AB  - Previous work suggests that social anxiety is inconsistently related to alcohol
      use. To further explore this relationship, alcohol outcome expectancies were
      evaluated as potential moderator and mediators in a large sample (N=284) of
      college undergraduates. The expectancy variables included positive and negative
      alcohol outcome expectancies as well as expectancies specific to social
      facilitation. Consistent with a self-presentation model of shyness, social
      anxiety was related to decreased drinking. Interestingly, social anxiety was
      associated with increased positive as well as increased negative expectancies.
      There was not support for moderator or mediator effects. Consistent with prior
      work, social facilitation expectancies appear to operate as a suppressor variable
      in the relationship between social anxiety and alcohol use.

PMID- 14725868
TI  - The relations of PTSD symptoms to alcohol use and coping drinking in volunteers
      who responded to the Swissair Flight 111 airline disaster.
AB  - We investigated the effects of the 1998 Swissair Flight 111 (SA 111) disaster on
      a variety of indices of alcohol use among volunteer responders. We
      retrospectively administered standardized questionnaires and a semi-structured
      interview to 13 volunteer disaster workers recruited from the community.
      According to the interview, 54% of the volunteers were exposed to human remains.
      According to Modified Post-Traumatic Stress Disorder (PTSD) Symptoms Scale
      responses, 46% met DSM-IV criteria for PTSD. Frequency and severity of PTSD
      symptoms, but not human remains exposure, per se, were positively correlated with
      coping-motivated drinking (but not social or mood enhancement drinking) and with
      alcohol use to forget. The re-experiencing and hyper-arousal PTSD symptom
      dimensions showed the strongest and most consistent correlations with the alcohol
      use indices. We discuss ways in which the information gleaned from this sample
      can be used to improve disaster response planning to minimize the probability of
      maladaptive coping drinking among volunteers.

PMID- 14725870
TI  - Marine pollution of a more ruthless kind.

PMID- 14725869
TI  - Internal cue exposure and the treatment of substance use disorders: lessons from
      the treatment of panic disorder.
AB  - Despite early recognition of the importance of internal cues (craving sensations
      and emotional states) for relapse in substance use disorders, relatively little
      attention has been devoted to exposure-based treatments targeting these cues.
      Drawing upon research on the conceptualization and treatment of panic disorder,
      we discuss the application of internal (largely emotional) cue exposure for
      substance use disorders. Our model for this discussion was based on the role of
      exposure to feared sensations of anxiety in the treatment of panic disorder and
      benzodiazepine (BZ) discontinuation. Shared research strategies between panic
      disorder and substance use--studies of biological provocation and anxiety
      sensitivity--were discussed, as were gender differences in drug-use motives. In
      accordance with research on anxiety sensitivity, provocation effects, and the
      treatment of benzodiazepine withdrawal, we discussed the potential value of
      internal cue-exposure strategies for individuals who use substances as a way to
      cope with negative affect.

PMID- 14725871
TI  - Seed supply for coastal brackishwater shrimp farming: environmental impacts and
      sustainability.
AB  - Globally, shrimp farming has been a significant agro-based economic activity
      since the early 1970s. Because it offered a huge immediate economic return,
      shrimp farming showed a booming expansion and soon became a multimillion dollar
      industry. However, it has been under extreme criticism because of its devastating
      ecological and socio-economic impacts. Because seed is the primary input, the
      impact from farming has started from the source of seed supply, so that not only
      are natural stocks of shrimp seeds now overexploited worldwide but seed
      collection activities also significantly reduce stocks of other living resources.
      Although hatcheries were developed as potential alternative and have replaced the
      natural seed source to a great extent, large-scale hatchery productions provide a
      potential source of coastal pollution. However, this area is still poorly
      studied. The present paper provides a review of the environmental impacts of the
      wild shrimp seed fishery as well as the possibility of environmental degradation
      from artificial shrimp seed production in hatcheries.

PMID- 14725872
TI  - Drill cutting accumulations in the Northern and Central North Sea: a review of
      environmental interactions and chemical fate.
AB  - The exploration and production of North Sea oil and gas reserves has resulted in
      the accumulation of large quantities of drill cuttings on the seabed surrounding
      drill sites. This complex mixture of man-made and natural substances contains
      higher concentrations of certain metals (Ba, Cr, Cu, Ni, Pb, and Zn) and
      hydrocarbons than are observed in background sediments. With decommissioning of
      older platforms underway, an evaluation of the environmental interactions and
      chemical fate of the drill cuttings accumulations is required. This review
      concentrates on contaminants within drill cutting accumulations in the Northern
      and Central North Sea (56 degrees N-62 degrees N). Present literature reviewed
      reveals that hydrocarbons within the cuttings piles remain relatively unchanged
      with time. A considerable proportion of the associated contaminants are likely to
      remain within the cuttings pile unless they are disturbed which will then
      increase exchanges of porewater and solids back to the seabed surface resulting
      in pathways of exposure for organisms.

PMID- 14725873
TI  - The Caspian Sea: a microcosm for environmental science and international
      cooperation.

PMID- 14725874
TI  - Organochlorinated compounds in Caspian Sea sediments.
AB  - Several organochlorinated contaminants, including numerous pesticides, were
      determined in coastal sediments from the Caspian Sea. The most important
      contaminants were p,p'-DDT (up to 7400 pg g(-1)) and its breakdown products, p,p'
      DDD (up to 3400 pg g(-1)) and p,p'-DDE (up to 1300 pg g(-1)). Although the
      contamination was most severe in Azerbaijan, the sediment concentrations and
      percentage distribution of the three DDT-related compounds indicated that such
      contamination constitutes a contemporary and ubiquitous problem in the Caspian
      Sea. Lindane represented the second most significant contaminant, particularly in
      the Russian Federation, with concentrations up to 609 pg g(-1). The
      concentrations of HCB and other chlorinated pesticides (cis- and trans-chlordane,
      methoxychlor, heptachlor, heptachlor epoxide, aldrin, endrin, and endosulfans)
      were lower and not generally of concern, but the pesticides did demonstrate
      markedly different distributions reflecting differing agricultural usage in the
      region. The concentrations of Sigma PCBs were also quite low and ranged from 0.03
      to 6.4 ng g(-1), with the highest amounts in the Russian Federation and
      Azerbaijan.

PMID- 14725875
TI  - Aliphatic and aromatic hydrocarbons in coastal Caspian Sea sediments.
AB  - This investigation represents the first extensive study of the spatial
      distribution and sources of aliphatic (n-alkanes and unresolved complex mixture
      of fossil hydrocarbons) and polycyclic aromatic hydrocarbons (PAHs) in coastal
      sediments from the Caspian Sea. PAH concentrations, n-alkanes and biomarker
      profiles all suggested that there was limited petrogenic contamination in the
      shallow North Caspian Sea sediments, which are coarse with a low total organic
      carbon content. In contrast, moderate to high petrogenic contamination was found
      in the South Caspian Sea, in particular in the offshore oil fields near Baku,
      Azerbaijan. Contaminant patterns indicated that the PAHs were mainly from fossil
      sources, with higher contributions of pyrolytic only near industrialized and
      urban areas. A high contribution of perylene, a geochemically derived PAH, to the
      total PAHs was found in the west and south at sites influenced by the Kura, Safid
      Rud, Terek, Sulak and Samur Rivers.

PMID- 14725876
TI  - An assessment of metal contamination in coastal sediments of the Caspian Sea.
AB  - An assessment of marine pollution due to metals was made in the Caspian Sea based
      on coastal sediment collected in Azerbaijan, Iran, Kazakhstan, Russia and
      Turkmenistan. Despite the high carbonate content, the distribution of most metals
      was largely controlled by terrigenous inputs. Several metals (As, Cr, Ni)
      exhibited concentrations that exceed sediment quality guidelines. Such metals
      have a high natural background but anthropogenic activities, notably mining, may
      further enhance concentrations. This would explain hot spots for Cu and Zn in
      Azerbaijan and Iran, and Cr at the mouth of the Ural River in Kazakhstan.
      Contamination by Hg was observed to the south of Baku Bay, Azerbaijan. Some
      anomalously high concentrations of Ba in the central Caspian are probably from
      offshore drilling operations, but the elevated U concentrations (up to 11.1
      microg g(-1)) may be natural in origin. Several metals (Ag, Cd, Pb) have
      relatively low levels that pose no environmental concerns.

PMID- 14725877
TI  - Dissolved and particulate fluxes of copper through the Morlaix river estuary
      (Brittany, France): mass balance in a small estuary with strong agricultural
      catchment.
AB  - Dissolved and particulate copper were measured over an annual cycle (12 surveys
      between February 1998 and January 1999) in the Morlaix Estuary (Brittany,
      France). These variations were investigated in both the water column and the
      benthic compartment in order to calculate fluxes of copper within estuary. In the
      water column, dissolved and particulate copper concentrations ranged from 0.6 to
      19.0 nM and from 0.03 to 2.3 micromol g(-1), respectively. In the benthic
      compartment, copper concentrations in superficial sediment varied from 0.04 to
      0.32 micromol g(-1) and from 7.6 to 80.5 nM in the pore waters. The results show
      that copper contents in the water column reached levels commonly observed in
      estuaries affected by heavy industrial activities. Agricultural activities,
      extensively developed on the drainage basin, may be responsible for the copper
      excess. Mass balance of copper indicates that the metal accumulated within the
      estuary with a rate ranging from 97 to 119 kg yr(-1).

PMID- 14725878
TI  - Major and trace elements in sediments of the Campeche Sound, southeast Gulf of
      Mexico.

PMID- 14725879
TI  - Foraminifers as indicators of marine pollution: a culture experiment with
      Rosalina leei.
AB  - In order to develop a viable foraminiferal proxy for heavy metal pollutants,
      juvenile specimens of Rosalina leei were subjected to different mercury
      concentrations (0-180 ng/l). Initially considerable growth was observed in
      specimens kept in saline water having a mercury concentration up to 100 ng/l. But
      with the gradual increase in concentration of mercury the growth rate started
      decreasing. Total growth achieved was significantly lower in case of specimens
      kept at relatively higher mercury concentrations then those maintained in normal
      saline water. The most significant result of this experiment was the addition of
      abnormal chambers in the specimens kept at higher mercury concentration. Later
      the specimens kept at highest concentration (180 ng/l) were subjected to
      progressively increasing concentration of mercury to see the further effects and
      it was found that the specimens were still living at as high a mercury
      concentration as 260 ng/l although there was no growth.

PMID- 14725880
TI  - Polycyclic aromatic hydrocarbons and changes in the trophic structure of
      polychaete assemblages in sediments of Todos os Santos Bay, Northeastern, Brazil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and the trophic structure of polychaete
      assemblages were studied in sediments at 28 stations in Todos os Santos Bay.
      Total PAH concentrations varied from 8 to 4163 ng g(-1) dry weight. The indexes
      used for the determination of PAH origin suggested both pyrolytic and petrogenic
      sources. A total of 397 individuals of polychaetes was recorded which were
      classified in three trophic groups. The PCA ordination resulted in the formation
      of three groups of stations, Group I characterised by sandy sediments, low
      organic content, low total PAH concentration and percentage of potentially
      harmful PAH was dominated by subsurface deposit-feeders. The other two groups
      (IIa and IIb), showed similar percentages of silt and clay, however, Group IIb
      formed by those stations with high total organic carbon, total nitrogen, sulphur
      contents, high total PAH concentration and percentage of potentially harmful PAH
      was dominated by carnivores. Trophic changes could be explained by the level of
      exposure to PAH effects relative to differences in the life style and feeding
      strategies between deposit-feeders and carnivores.

PMID- 14725881
TI  - Comparison of the lethal effect of CO2 and acidification on red sea bream (Pagrus
      major) during the early developmental stages.
AB  - To compare the acute toxicity of CO(2)- and HCl-acidified seawater, eggs and
      larvae of a marine fish, Pagrus major, were exposed to seawater equilibrated with
      CO(2)-enriched gas mixtures (CO(2)=5% or 10%, O(2)=20.95% balanced with N(2)) or
      seawater acidified with 1 N HCl at two pH levels (pH 6.2 (=5% CO(2)) and 5.9
      (=10% CO(2))) for 6 h (eggs) or 24 h (larvae). Mortalities of eggs were 85.8%
      (CO(2)) and 3.6% (HCl) at pH 6.2, and 97.4% (CO(2)) and 0.9% (HCl) at pH 5.9,
      while those of larvae were 61.2% (CO(2)) and 1.6% (HCl) at pH 6.2, and 100%
      (CO(2)) and 5.0% (HCl) at pH 5.9. Thus, previous research on the effects of
      acidified seawater on marine organisms, as a substitute for CO(2), has largely
      underestimated the toxic effects of CO(2).

PMID- 14725882
TI  - Persistent halogenated compounds in black guillemots (Cepphus grylle) from
      Greenland--levels, compound patterns and spatial trends.
AB  - Twenty-seven black guillemot eggs and 39 livers were analysed for polychlorinated
      biphenyls (PCBs), chlorinated pesticides including chlordane-related compounds
      and toxaphene, and polybrominated diphenylethers (PBDEs). The samples were
      collected at Qeqertarsuaq (Godhavn, West Greenland) and Ittoqqortoormiit
      (Scoresbysund, East Greenland). The concentrations of halogenated organic
      compounds in samples from East Greenland were somewhat higher than the
      corresponding concentrations from West Greenland. Differences in compound
      patterns were found between West and East Greenland, with higher percentages of
      the heavier PCB molecules, p,p(')-DDE and alpha-HCH in the samples from
      Ittoqqortoormiit. Similarly, different levels and different compositions were
      observed for eggs and livers. The eggs had generally higher concentrations of all
      compounds as well as higher percentages of CHB-50, CHB-62 and alpha-HCH than
      liver samples from the same area. Dividing the liver samples into age groups
      revealed increasing concentrations with age.

PMID- 14725883
TI  - The Eurobulker oil spill: mid-term changes of some ecosystem indicators.
AB  - The sinking of the tanker Eurobulker in Southern Evoikos gulf (Aegean Sea,
      Greece) in September 2000 resulted in a spill of 700 tons of crude oil. The
      environmental impact of the spill was studied by the National Centre for Marine
      Research. The hydrocarbon concentrations in water, sediment and coastal benthic
      organisms were measured and the response of the benthic communities to the
      disturbance caused by the oil spill was studied along the direction to the coast
      and over three sampling seasons. The most severe and direct effects were
      evidenced on the muddy benthic communities of the accident site and the stations
      in the close vicinity sampled shortly after the spill. The effects included
      reduction of the species richness and community diversity, but the communities
      reached full recovery 8 months later. The impact of the spill was more indirect
      and delayed in the coastal stations, where as the hydrocarbon measurements
      indicated, the pollutants were transported later and induced their effects on the
      benthic communities 6 months after the accident.

PMID- 14725884
TI  - Impacts of beach closures on perceptions of swimming-related health risk in
      Orange County, California.
AB  - Following a major beach closure due to bacterial contamination, a survey of
      beachgoers was conducted in Huntington Beach, California in 1999 to assess
      perceived health risk from swimming. Responses were compared to those of
      beachgoers at the unaffected Laguna Main Beach. No significant differences were
      found in risk perception. Respondents were aware of the closures (83%), yet the
      majority (83%) felt the water was safe for swimming. Proximity of residence to
      the beach was strongly associated with closure awareness (Spearman's rho=0.427,
      p<0.0001). Although 83% of respondents felt that water quality was important in
      deciding to go to the beach, only 25% of respondents who did not plan to swim
      cited pollution or contamination as a reason not to swim. Most respondents (70%)
      trusted local health agency officials' decisions about when to open/close
      beaches. Surveyed beach visitors were likely to bathe (84%) and were not highly
      concerned with swimming-related health risks.

PMID- 14725885
TI  - Nitrogen loading to Pleasant Bay, Cape Cod: application of models and stable
      isotopes to detect incipient nutrient enrichment of estuaries.
AB  - To test and refine methods to detect nutrient enrichment and resulting
      eutrophication, we applied the Waquoit Bay nitrogen loading model (NLM) and
      Estuarine loading model (ELM) to estuaries of Pleasant Bay that receive
      increasing but low N loads (25-199 kg N ha(-1) yr(-1)) from land. Contributions
      of wastewater to these estuaries increased from 7% to 63% as N loads increased,
      and modeled estimates of dissolved inorganic nitrogen in the water were within
      approximately 27% of measured values. N isotopic signatures in suspended and
      benthic organic matter and in tissue of quahogs increased as wastewater
      contributions to N loads increased, with clams approximately 4 per thousand
      heavier than organic matter, indicating that even at these low N loads, N from
      land-derived sources moved detectably up the food web. These results extend the
      application of NLM and ELM to detect incipient levels of N enrichment and
      demonstrate that these models can be used in conjunction with isotope
      measurements as the basis for food web analyses in a system exposed to relatively
      lower N loads than previously studied.

PMID- 14725886
TI  - Sediment quality in the Guadalquivir estuary: lethal effects associated with the
      Aznalcollar mining spill.
AB  - Monitoring from 1998 to 2001 has assessed the impact of the Aznalcollar mining
      spill on the sediment quality in the Guadalquivir estuary. Chemical analysis has
      been completed with biological effects measured in different organisms. The
      toxicity of sediments obtained from dilutions of toxic mud and from environmental
      stations affected by the accidental spill was tested using the amphipod Ampelisca
      brevicornis and the clam Scrobicularia plana. The results obtained show that
      amphipods are more sensitive to the accidental spill than the clams. A dilution
      of clean sediment by more than 1.8% of toxic mud produced 100% mortality of
      amphipods. In GR2 station is detected toxicity to amphipods but not to clams. The
      rest of the environmental stations show no toxicity. Toxicity to amphipods in GR2
      station decreased along time (from 50% to 60% of mortality in 1998 to 10 to 15%
      in 2001) and it can be associated with a recovery of the areas impacted by the
      accidental spill.

PMID- 14725887
TI  - Sediment quality in the Guadalquivir estuary: sublethal effects associated with
      the Aznalcollar mining spill.
AB  - As a complementary assessment of the impact of the Aznalcollar mining spill on
      the Guadalquivir estuary two different sediment toxicity tests using fish (Solea
      senegalensis) and clams (Scrobicularia plana) were performed. The
      histopathological alterations by recording lesions at 15 and 30 days in fish to
      the gills, liver, gut and kidney and at 14 days in clams to the gills and gut
      were used to determine the adverse effects associated with the contaminants bound
      to sediments. The lesions measured at different tissues in both organisms show
      that the enrichment of heavy metals from the mining spill stressed some areas in
      the ecosystem of the estuary. The comparison of these effects with those lethal
      effects detected in the same samples using a multivariate analysis approach
      permits to identify the adverse effects associated with the accidental spill on
      the estuary. The incidence of the impact, located in specific areas of the
      estuary show an acute effect related to the spill.

PMID- 14725888
TI  - Persistent organic pollutants in rough-toothed dolphins (Steno bredanensis)
      sampled during an unusual mass stranding event.

PMID- 14725889
TI  - Trace element residues in tissues of green turtles (Chelonia mydas) from South
      China waters.

PMID- 14725890
TI  - Effects of chlorpyrifos on the endogenous rhythm of the Manila clam, Ruditapes
      philippinarum (Bivalvia: Veneridae).

PMID- 14725891
TI  - Limited effectiveness of marine protected areas: imposex in Hexaplex trunculus
      (Gastropoda, Muricidae) populations from Italian marine reserves.

PMID- 14725892
TI  - Phosphorus-rich waters at Glovers Reef, Belize?

PMID- 14725894
TI  - The changing of the guard.

PMID- 14725895
TI  - Chronic myeloid leukemia-still a few questions.
AB  - The study of chronic myeloid leukemia has yielded many insights, especially after
      the discovery of the Ph chromosome, into the pathogenesis of leukemia and other
      forms of malignant disease. Most recently, knowledge of the central function of
      the BCR-ABL fusion gene led to the development of a small molecule, imatinib,
      that has proved remarkably effective at reducing the number of leukemia cells in
      individual CML patients and promises to prolong life substantially in comparison
      with earlier treatments. However, many questions relating to this exciting new
      agent remain unanswered, for example, how exactly it works, how patients develop
      resistance and what can be done to prevent or delay its onset, and whether any
      patient can really be "cured" by its use.

PMID- 14725896
TI  - SCL: from the origin of hematopoiesis to stem cells and leukemia.
AB  - In the hematopoietic system, lineage commitment and differentiation is controlled
      by the combinatorial action of transcription factors from diverse families. SCL
      is a basic helix-loop-helix transcription factor that is an essential regulator
      at several levels in the hematopoietic hierarchy and whose inappropriate
      regulation frequently contributes to the development of pediatric T-cell acute
      lymphoblastic leukemia. This review discusses advances that have shed important
      light on the functions played by SCL during normal hematopoiesis and
      leukemogenesis and have revealed an unexpected robustness of hematopoietic stem
      cell function. Molecular studies have unraveled a mechanism through which gene
      expression is tightly controlled, as SCL functions within multifactorial
      complexes that exhibit an all-or-none switch-like behavior in transcription
      activation, arguing for a quantal process that depends on the concurrent
      occupation of target loci by all members of the complex. Finally, variations in
      composition of SCL-containing complexes may ensure flexibility and specificity in
      the regulation of lineage-specific programs of gene expression, thus providing
      the molecular basis through which SCL exerts its essential functions at several
      branch points of the hematopoietic hierarchy.

PMID- 14725897
TI  - Perspective: stem cells react! Cell lineages as complex adaptive systems.
AB  - It may be argued that adult stem cell processes or, more precisely, the cell
      lineages that arise from them, represent complex reactive or adaptive systems.
      Approaching hematopoietic and other stem cell lineages from this perspective has
      direct bearing on current debates regarding the plasticity of these lineage
      systems as well as on interpretation and modeling of clinical data regarding many
      diseases.

PMID- 14725898
TI  - Nonablative allogeneic stem cell transplantation for chronic lymphocytic
      leukemia: impact of rituximab on immunomodulation and survival.
AB  - OBJECTIVE: To investigate the graft-vs-leukemia effect of allogeneic stem cell
      transplantation after a nonablative conditioning regimen as treatment for
      patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Patients were
      eligible to treatment if they were refractory or recurred after a prior response
      to fludarabine. Seventeen patients were treated. All patients received a
      preparative regimen of fludarabine (30 mg/m(2) daily for 3 days) and intravenous
      cyclophosphamide (750 mg/m(2) daily for 3 days). Ten patients received rituximab
      in addition to chemotherapy. The median time from diagnosis to transplant was 67
      months. Nine of 17 patients had refractory disease. RESULTS: All patients had
      engraftment of donor cells. Eleven (65%) did not require platelet transfusions.
      Ten patients with persistent disease underwent immunomanipulation to augment GVL
      effects including immunosuppression withdrawal and donor lymphocyte infusion with
      or without rituximab treatment. Seven of these 10 patients had a complete
      response and 2 had a partial response; 8 of these 9 responders had received
      rituximab with their immunomanipulation process. The final response was complete
      remission in 12 and partial remission in 4 patients for an overall response rate
      of 94%. Overall survival was 100% for patients who received the combined chemo
      rituximab conditioning regimen, vs 14% for those who received chemotherapy alone
      (p=0.03). CONCLUSION: Our results indicate that a pronounced GVL effect occurs
      after nonmyeloablative allogeneic hematopoietic transplantation for advanced CLL.
      This activity might be facilitated by rituximab. Prospective controlled trials
      are needed to define the role of nonablative allogeneic hematopoietic
      transplantation for treatment of this disease.

PMID- 14725900
TI  - All-trans retinoic acid directly up-regulates thrombopoietin transcription in
      human bone marrow stromal cells.
AB  - OBJECTIVE: All-trans retinoic acid (ATRA) has been used as the first-line therapy
      for patients with acute promyelocytic leukemia (APL). We previously reported that
      ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis
      during ATRA therapy for APL. In this study, we investigated the mechanism of
      transcriptional regulation of TPO gene by ATRA using human bone marrow stromal
      cells. PATIENTS AND METHODS: Real time reverse transcriptase polymerase chain
      reaction and Western blotting were performed to quantify TPO mRNA and protein
      levels in cells from the human bone marrow stromal cell line KM101. Luciferase
      based reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin
      immunoprecipitation (ChIP) assay were performed to identify a retinoic acid
      responsive element in the promoter region of TPO gene (TPO-RARE). RESULTS: TPO
      mRNA expression was up-regulated by approximately 2.9 times 8 hours after
      stimulation with 10(-6) M ATRA in KM101 cells. In contrast, ATRA did not alter
      TPO mRNA expression in cells from the human hepatoma cell line HepG2. Protein
      level of KM101 cells also was increased with 10(-6) M ATRA for 48 hours in KM101
      cells. We found the synthesized RARalpha protein bound to [gamma-32P]-labeled TPO
      RARE probe and its binding was competed by adding 200x amount of cold TPO-RARE
      probe by EMSA. In addition, [gamma-32P]-labeled TPO-RARE probe bound to KM101
      nuclear protein extract was supershifted by anti-RARalpha antibody and modified
      by treatment with ATRA. The relative luciferase activity of TPO gene was
      increased by 2.2x and the histone H4 was acetylated through TPO-RARE after ATRA
      stimulation in KM101 cells by ChIP assay. CONCLUSION: These data support the
      direct up-regulation of TPO transcription by ATRA stimulation in human bone
      marrow stromal cells and propose one of the mechanisms of thrombocytosis during
      ATRA therapy for APL.

PMID- 14725899
TI  - Opposing effects of PI3 kinase pathway activation on human myeloid and erythroid
      progenitor cell proliferation and differentiation in vitro.
AB  - OBJECTIVE: To investigate 1) the effects of lineage-specific cytokines (G-CSF and
      EPO) combined with ligands for different classes of cytokine receptors (common
      beta chain, gp130, and tyrosine kinase) on proliferation by human myeloid and
      erythroid progenitor cells; and 2) the signal transduction pathways associated
      with combinatorial cytokine actions. PATIENTS AND METHODS: CFU-GM and BFU-E were
      cloned in vitro. Secondary colony formation by replated CFU-GM and subcolony
      formation by BFU-E provided measures of progenitor cell proliferation. Studies
      were performed in the presence of cytokine combinations with and without signal
      transduction inhibitors. RESULTS: Proliferation by CFU-GM and BFU-E was enhanced
      synergistically when common beta chain receptor cytokines (IL-3 or GM-CSF) were
      combined with G-CSF or EPO, but not with gp130 receptor cytokines (LIF or IL-6)
      or tyrosine kinase receptor cytokines (SCF, HGF, Flt-3 ligand, or PDGF). Delayed
      addition studies with G-CSF+IL-3 and EPO+IL-3 demonstrated that synergy required
      the presence of both cytokines from the initiation of the culture. The Jak2
      specific inhibitor, AG490, abrogated the effect of combining IL-3 with EPO but
      had no effect on the enhanced CFU-GM proliferation stimulated by IL-3+G-CSF. The
      PI3 kinase inhibitors LY294002 and wortmannin substituted for G-CSF in
      combination with IL-3 since proliferation in the presence of
      LY294002/wortmannin+IL-3 was enhanced to the same extent as in the presence of G
      CSF+IL-3. In contrast, LY294002 and wortmannin inhibited proliferation in the
      presence of EPO and in the presence of EPO+IL-3. CONCLUSION: 1) IL-3 may activate
      different signal transduction pathways when combined with G-CSF and when combined
      with EPO; 2) different signal transducing intermediates regulate erythroid and
      myeloid progenitor cell proliferation; and 3) inhibition of the PI3 kinase
      pathway suppresses myeloid progenitor cell differentiation and thereby increases
      proliferation.

PMID- 14725901
TI  - Interleukin-4 elicits apoptosis of developing mast cells via a Stat6-dependent
      mitochondrial pathway.
AB  - OBJECTIVE: The aim of this study was to assess the effects of interleukin-4 and
      signal transducer and activator of transcription (Stat)-6 on IL-3+SCF-induced
      mast cell development. PATIENTS AND METHODS: Unseparated mouse bone marrow cells
      were cultured in IL-3+SCF, giving rise to mast cells and monocytes/macrophages.
      The addition of IL-4, the use of Stat6-deficient bone marrow cells, and
      expression of a constitutively active Stat6 mutant were employed to assess the
      effects of IL-4 and Stat6 on cell viability, proliferation, and differentiation.
      Bax-deficient and bcl-2 transgenic bone marrow cells were used to assess the
      importance of the mitochondria in IL-4-mediated effects. RESULTS: IL-4 elicited
      apoptosis and limited the cell cycle progression of developing bone marrow cells,
      without affecting cell differentiation. Apoptosis required that IL-4 be present
      during the first 8 days of the 21-day culture period. Cell death correlated with
      loss of mitochondrial membrane potential. Accordingly, IL-4-mediated apoptosis
      was inhibited by Bax deletion or bcl-2 overexpression. Lastly, Stat6 activation
      was both necessary and sufficient to inhibit cell survival. CONCLUSION: IL-4
      exerts potent apoptotic effects on developing mast cells and monocyte/macrophages
      through mitochondrial damage and Stat6 activation.

PMID- 14725902
TI  - Genetic analysis of progenitor cell mobilization by granulocyte colony
      stimulating factor: verification and mechanisms for loci on murine chromosomes 2
      and 11.
AB  - OBJECTIVE: It is notable that there is significant inter-individual variability
      in humans and inter-strain variability in mice in the ability to mobilize
      hematopoietic stem and progenitor cells, suggesting that there is genetic
      regulation of mobilization. In the murine system, loci on chromosomes 2 and 11
      have been linked to an inter-strain variation in granulocyte colonystimulating
      factor (G-CSF)-induced stem cell mobilization proficiency. The aim of this study
      was to verify this linkage and to gain insight into the function of these loci.
      METHODS: Animals congenic for the loci on chromosomes 2 and 11 were generated by
      a speed-congenic approach and the function of the loci were further analyzed in
      doubly congenic animals and with a competitive transplantation/mobilization
      protocol. RESULTS: The analysis of congenic animals verified that both loci are
      linked to mobilization proficiency. Analysis of mobilization in doubly congenic
      animals suggested that both loci act in the same regulatory pathway. Mobilization
      experiments conducted with mice that had previously been competitively
      repopulated with congenic and parental-strain BM revealed that the locus on
      chromosome 11 operates via a progenitor cell-intrinsic mechanism. CONCLUSION: We
      confirmed linkage of loci on chromosomes 2 and 11 to G-CSF-induced mobilization
      and thus validated their role as regulators of hematopoietic progenitor cell
      mobilization in mice. These findings will be useful for further studies directed
      at identifying genes that regulate mobilization proficiency.

PMID- 14725903
TI  - Mobilization of primitive and committed hematopoietic progenitors in nonhuman
      primates treated with defibrotide and recombinant human granulocyte colony
      stimulating factor.
AB  - OBJECTIVE: The aim of this study was to evaluate the capacity of defibrotide in
      enhancing cytokine-induced hematopoietic mobilization in rhesus monkeys.
      MATERIALS AND METHODS: Animals received recombinant human granulocyte colony
      stimulating factor (rhG-CSF, 100 microg/kg/day SC for 5 days) and, after a 4- to
      6-week washout period, were remobilized with defibrotide (15 mg/kg/hour
      continuous intravenous for 5 days) plus rhG-CSF. Hematopoietic mobilization was
      evaluated by complete blood counts, differential counts, as well as frequency and
      absolute numbers of colony-forming cells (CFCs), high-proliferative potential
      CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). RESULTS:
      Compared to baseline values, rhG-CSF increased circulating CFCs, HPP-CFCs, and
      LTC-ICs by 158-, 125-, and 67-fold, respectively; the same figures for
      defibrotide/rhG-CSF were 299-, 1452-, and 295-fold, respectively. Defibrotide/rhG
      CSF treatment compared to rhG-CSF alone increased CFCs, HPP-CFCs, and LTC-ICs by
      1.4- (35,089 vs 25,825, p< or =0.02), 6- (4358 vs 748, p< or =0.02), and 5-fold
      (884 vs 168, p< or =0.04), respectively. We then evaluated the effects of a 2-day
      defibrotide treatment associated with a 5-day rhG-CSF treatment. Compared to rhG
      CSF, defibrotide/rhG-CSF increased the mobilization of CFCs, HPP-CFCs, and LTC
      ICs by 2- (31,128 vs 15,527, p< or =0.05), 8- (5361 vs 660, p< or =0.01), and 8
      fold (954 vs 119, p< or =0.01), respectively. CONCLUSION: Our data demonstrate
      that in nonhuman primates: 1) defibrotide enhances rhG-CSF-elicited mobilization
      of primitive and committed progenitors; and 2) a 2-day defibrotide injection is
      as effective as a 5-day injection.

PMID- 14725904
TI  - Treosulfan-induced apoptosis in acute myeloid leukemia cells is accompanied by
      translocation of protein kinase C delta and enhanced by bryostatin-1.
AB  - OBJECTIVE: Acute myeloid leukemia (AML) still is fatal in the majority of
      patients. Therefore, we evaluated the antileukemic effect of the alkylating agent
      treosulfan in AML. MATERIALS AND METHODS: Chemosensitivity tests were performed
      in AML cell lines and primary cells from patients. Because protein kinase C (PKC)
      is known to play an integral role in the regulation of diverse cellular functions
      such as apoptosis, several PKC modulators were evaluated in conjunction with
      treosulfan. RESULTS: U937, THP-1, HL-60, TUR cells, and primary AML cells
      obtained from five consecutive patients displayed dose-dependent sensitivity to
      treosulfan. The LC(90) was approximately 100 microM, which is several fold below
      clinically achievable plasma levels. Cell death was associated with cellular
      events indicating apoptosis such as breakdown of the mitochondrial transmembrane
      potential, proteolytic activation of caspase-3, or appearance of a sub-G(1) DNA
      peak. Synergistic antileukemic effects were observed in all cell lines and
      patient samples tested using the PKC activators bryostatin-1 and 12-O
      tetradecanoylphorbol-13-acetate (TPA), whereas the PKC inhibitor GF109203X
      substantially reduced apoptosis. Furthermore, long-term preincubation with
      bryostatin-1 or TPA, both of which are known to down-regulate PKC protein levels,
      likewise inhibited treosulfan-induced apoptosis. Immunoblots revealed membrane
      translocation of PKC-delta, indicating activation of this enzyme upon treosulfan
      exposure. CONCLUSION: Our data provide evidence for a strong antileukemic effect
      of treosulfan in both cell lines and AML blasts from patients at concentrations
      below the plasma levels described at standard dose levels. Furthermore, the
      proapoptotic effect of treosulfan is mediated at least in part by activation of
      PKC isoforms and can be augmented by coincubation with bryostatin-1.

PMID- 14725905
TI  - New model of transient strain-dependent autoimmune thrombocytopenia in mice
      immunized with rat platelets.
AB  - OBJECTIVE: The aim of this study was to develop a new experimental model of
      antiplatelet autoimmune disease in the mouse. MATERIALS AND METHODS: Mice were
      immunized with rat platelets. Anti-mouse platelet autoantibody responses were
      analyzed by enzyme-linked immunosorbent assay, Western blots, and flow cytometry.
      RESULTS: Immunization of CBA/Ht mice with rat platelets was followed by a
      transient thrombocytopenia. Platelets were opsonized by autoantibodies that
      recognized both rat and mouse normal platelets and (then) destroyed by
      phagocytosis. Absorption experiments indicated that these autoantibodies reacted
      with epitope(s) shared by rat and mouse platelets. In contrast, BALB/C mice
      similarly immunized with rat platelets did not develop thrombocytopenia. The
      ability of BALB/C mice to produce anti-rat platelet antibodies and to eliminate
      antibody-coated platelets was comparable with that of CBA/Ht animals. However,
      the specificity of the antibody response elicited in these two mouse strains
      differed markedly, with a 145- to 155-kDa mouse platelet antigen corresponding to
      platelet glycoprotein Ib recognized in CBA/Ht, but not in BALB/C, animals.
      CONCLUSION: This immunization protocol may serve as a model of antiplatelet
      autoimmune response, especially of posttransfusion purpura.

PMID- 14725906
TI  - Induction of cytomegalovirus-specific CD4+ cytotoxic T lymphocytes from
      seropositive or negative healthy subjects or stem cell transplant recipients.
AB  - OBJECTIVE: We generated cytomegalovirus (CMV)-specific cytotoxic T lymphocytes
      (CTL) in vitro using dendritic cells (DC) pulsed with crude CMV antigens (Ag).
      PATIENTS AND METHODS: Mononuclear cells from healthy CMV-seropositive or
      seronegative volunteers and from stem cell transplant (SCT) recipients were
      cultured with CD14(+) monocyte-derived DC prepulsed with CMV Ag and then matured
      in vitro with lipopolysaccharide and tumor necrosis factor-alpha. After
      proliferation, cells were checked for phenotype (CD4/CD8), while killing activity
      was measured by 51Cr-release assay. RESULTS: CD4(+) T cells, the main
      proliferating cells from both seropositive and seronegative individuals, killed
      autologous Ag-pulsed DC but not vehicle-pulsed autologous DC or CMV-pulsed
      allogeneic DC. Similar CTL induction was accomplished from SCT recipients.
      Significant killing of autologous CMV-infected fibroblasts required 16-hour
      incubation as opposed to the standard 4-hour incubation, which was prevented by
      either a perforin inhibitor or anti-Fas ligand monoclonal antibody. CTL enhanced
      surface HLA-DR expression of CMV-infected fibroblasts, and their activity was
      neutralized by anti-HLA-DR monoclonal antibody. CONCLUSION: CMV-specific CD4(+)
      CTL were inducible with or without antiviral humoral immunity, even from
      immunosuppressed SCT recipients. These CTL showed perforin- and Fas/Fas ligand
      mediated cytotoxicity after long-term (16-hour) contact with CMV-infected
      targets.

PMID- 14725907
TI  - Analysis of transcription factors in thymic and CD34+ progenitor-derived
      plasmacytoid and myeloid dendritic cells: evidence for distinct expression
      profiles.
AB  - OBJECTIVE: The expression of mRNA for pre-Talpha is specific for human
      plasmacytoid dendritic cells (PDC), a population ontogenically close to T cells.
      The latter need Gata-3 transcription factor to develop. PU1 and RelB are two
      transcription factors involved in the development of murine myeloid DC (MDC). To
      determine the lineage origin of human thymic DC, the expression of these genes
      was investigated. MATERIALS AND METHODS: Fresh thymic DC, CD34(+)CD1a(-)
      progenitors, and progenitor-derived DC populations were sorted, analyzed, and
      compared to blood DC. RESULTS: Three DC populations were found in the thymus. 1)
      CD123(-/lo)HLA-DR(hi) DC expressing PU1 and RelB; 2) CD123(hi)HLA-DR(+) DC
      expressing only pre-Talpha, the expression of which was similar to that of MDC
      and PDC from peripheral blood; and 3) a new mature CD123(hi)HLA-DR(hi) PDC
      population with pre-Talpha, PU1 and RelB mRNAs. In culture, most CD34(+)CD1a(-)
      progenitors remained CD1a(-)CD123(-); had a T and natural killer cell
      differentiation potential; and expressed Gata-3 mRNA contrary to DC precursors. A
      few cells (10%) became CD1a(+)CD123(+) expressing pre-Talpha, PU1, and RelB mRNAs
      and were able to differentiate into typical Langerhans cells with transforming
      growth factor-beta. Coculture of thymic progenitors on a murine cell line
      generated CD123(hi)CD1a(-) cells with typical PDC morphology, expressing pre
      Talpha but not PU1 and RelB transcripts. Activated PDC acquired myeloid antigens,
      and up-regulated PU1 and RelB mRNAs while down-regulating pre-Talpha mRNA
      expression. CONCLUSION: Both DC maturation pathways may arise from distinct
      precursors but are interconnected. DC differentiation seems to occur from Gata-3(
      ) precursors upstream of T and natural killer precursors.

PMID- 14725908
TI  - Coexistence of phosphotyrosine-dependent and -independent interactions between
      Cbl and Bcr-Abl.
AB  - Cbl is one of the major tyrosine-phosphorylated proteins in Bcr-Abl-expressing
      cells. A direct association between the SH2 domain of Bcr-Abl and tyrosine
      phosphorylated Cbl has been demonstrated. The purpose of this study was to
      determine if and how unphosphorylated Cbl and Bcr-Abl may associate. Interactions
      between Cbl and Bcr-Abl were investigated in yeast two- and three-hybrid systems,
      gel overlay assays, and immunoprecipitates from mammalian cells expressing wild
      type and the Y177F mutant of Bcr-Abl. No direct interaction between Bcr-Abl and
      unphosphorylated Cbl was observed. Bcr-Abl did, however, associate with Grb2, an
      adaptor protein that binds tyrosine 177 of Bcr-Abl. Additionally, Grb2 interacted
      with Cbl. In a yeast three-hybrid assay, Grb2 mediated an interaction between Cbl
      and Bcr-Abl that was dependent on a functional Grb2 binding site. This
      interaction was confirmed in vitro using purified proteins. In cells expressing
      Bcr-Abl with a mutation in the Grb2 binding site, binding of Cbl to Bcr-Abl was
      significantly reduced, but Cbl tyrosine phosphorylation was maintained. Imatinib
      treatment of these cells further reduced but did not abrogate Cbl binding,
      reflecting residual kinase activity. Multiple phosphotyrosine-dependent and 
      independent interactions stabilize the interaction between Cbl and Abl. Grb2 or
      another, yet unidentified, protein may mediate an initial interaction between Cbl
      and Bcr-Abl that is independent of Cbl tyrosine phosphorylation. Following this
      initial interaction, Cbl can then become tyrosine phosphorylated and interact
      with the SH2 domain of Bcr-Abl, further stabilizing the complex.

PMID- 14725909
TI  - Granulocyte colony-stimulating factor generates epigenetic and genetic
      alterations in lymphocytes of normal volunteer donors of stem cells.
AB  - OBJECTIVE: Because the effect of granulocyte colony-stimulating factor (G-CSF),
      which is widely used for allogeneic stem cell transplantation, on DNA function
      and stability has not yet been unequivocally elucidated, the aim of this study
      was to determine whether G-CSF leads to epigenetic and/or genetic modifications.
      MATERIALS AND METHODS: Molecular cytogenetic techniques based on fluorescence in
      situ hybridization technology were used. RESULTS: Lymphocytes of G-CSF mobilized
      donors displayed epigenetic (altered replication timing of alleles) and genetic
      (aneuploidy) alterations similar to those observed in lymphocytes of cancer
      patients. Specifically, in the donors' lymphocytes, biallelically expressed genes
      (TP53 and AML1) and a repetitive noncoding DNA sequence associated with
      chromosome segregation (CEN17) showed loss of synchrony in allelic replication
      timing (allele-specific replication). Each displayed a highly asynchronous
      pattern of allelic replication similar to that characterizing monoallelic
      expressed genes. This non-locus-specific epigenetic phenomenon, which also
      affects DNA sequences associated with chromosome segregation, was accompanied by
      aneuploidy. Although the loss of replication synchrony in the lymphocytes of G
      CSF mobilized donors was a transient epigenetic modification, aneuploidy remained
      unchanged. The G-CSF effect also was observed after G-CSF administration in
      vitro. 5-Azacytidine, a DNA methylation blocking agent, inhibited G-CSF in vitro
      induction of allele-specific replication. CONCLUSION: G-CSF, probably via changes
      in DNA methylation capacity, leads to cancer-characteristic DNA modifications in
      lymphocytes of normal mobilized donors.

PMID- 14725910
TI  - [Re-irradiation after salvage mastectomy for local recurrence after a
      conservative treatment: a retrospective analysis of twenty patients (Nancy: 1988
      2001)].
AB  - PURPOSE: To retrospectively assess the efficacy of post-mastectomy re-irradiation
      for local relapse of breast cancer. PATIENTS AND METHODS: Twenty patients,
      initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions
      over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage
      mastectomy and re-irradiation (either electron or photon beams). Mean age was 53
      years (31-71). Reasons for re-irradiation were that the local relapses were
      inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple
      (3 pts) or because the surgical margins (either muscle or skin) were involved (3
      pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33
      days. Mean follow-up was 48 months (5-97). RESULTS: Fifteen patients remained
      free of a second local recurrence and 10 were still alive, without metastasis.
      Neither the dose of re-irradiation nor the irradiated surfaces were prognostic
      factors of local control (P = 0.877 and P = 0.424). Five patients developed
      radiation-induced pneumonitis without functional respiratory impairment. The
      incidence of pneumonitis seemed to be related to the biological dose of re
      irradiation (P = 0.037). Other late complications occurred such as pigmentation
      changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis
      (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The
      increase in biological equivalent dose was highly statistically linked with the
      occurrence of disabling pain (P = 0.0123). CONCLUSION: Parietal re-irradiation
      achieves good and lasting local control with an acceptable rate of acute
      complications but with a risk of disabling late sequelae such as severe pain.

PMID- 14725911
TI  - Cancer of the larynx in females.
AB  - PURPOSE: The aim of this paper is to present results of analysis of 102 females
      with laryngeal cancer. MATERIALS AND METHODS: Between 1974 and 1995, 102 female
      patients with cancer of larynx were treated at Radiotherapy Department of
      Oncology Centre in Krakow. Twenty-six of them had positive familial oncological
      history. The treatment method depended on stage of disease. Primary radical
      irradiation was performed in 66 patients, 29 patients received postoperative
      radiotherapy after surgery (total or partial laryngectomy), seven patients
      received induction chemotherapy followed by laryngectomy with postoperative
      radiotherapy or radical irradiation. The median dose applied with radiotherapy
      was 60 Gy, and dose per fraction was 2 Gy. RESULTS: The actuarial 5-year rates
      were as follows: 88.9% for overall survival, 84.2% for disease-free survival, and
      85.4% for local control. Only tumour stage and nodal involvement were found to be
      significant factor for all three endpoints. We found that younger patients had
      more supraglottic primary localisation, and these patients frequently were non
      smoker. CONCLUSIONS: The tumour stage and nodal involvement were found to be
      significant prognostic factors in analysed group of female treated with laryngeal
      cancer.

PMID- 14725914
TI  - [European Core Curriculum for Radiotherapy technologists].

PMID- 14725912
TI  - [Radiotherapy in stage I testicular seminoma: retrospective study and review of
      literature].
AB  - INTRODUCTION: Seminoma accounts for about 40% of germ cell tumours of the
      testicle. In this retrospective analysis, we review literature concerning
      management of stage I seminoma. MATERIALS AND METHODS: Between March 1987 and
      April 2001, 65 patients with stage I pure testicular seminoma received adjuvant
      radiotherapy with a 25 MV linear accelerator. RESULTS: Median age was 33 years.
      Testicular tumour has been found on the right testis in 39 patients and on the
      left one in 24 patients. Patients have been treated using an anterior-posterior
      parallel pair and have received 20-25 Gy in 10-14 fractions. The target volume
      consisted of paraaortic, and paraaortic + homolateral iliac lymph nodes in 17 and
      46 patients, respectively. Acute toxicity was mainly digestive, 38% of patients
      presenting nausea and vomiting. Median follow-up time was 37 months. All patients
      are alive in complete remission. DISCUSSION: Because of good radio-sensitivity of
      seminoma, radiotherapy is regarded as standard adjuvant treatment (5 years
      relapse rate: 3-5%). Acute toxicity is dominated by moderate gastro-intestinal
      side effects. Secondary neoplasia represents one of the worst possible long-term
      complications of therapy. Waiting for ongoing randomised trials, the modern
      literature for seminoma reflects a trend toward lower radiation doses (20-25 Gy)
      and smaller treatment volumes (paraaortic field). Adjuvant chemotherapy with two
      courses of carboplatin, might be equivalent to radiotherapy but must be
      investigated in randomised trials. A surveillance policy is one of the other
      management options less recommended.

PMID- 14725917
TI  - New NMR strategies for brain investigation.

PMID- 14725919
TI  - Thresholding in correlation analyses of magnetic resonance functional
      neuroimaging.
AB  - The definition of objective and effective thresholds in MRI of human brain
      function is a crucial step in the analysis of paradigm-related activations. This
      paper introduces a user-independent and robust procedure that calculates
      statistical parametric maps based on correlation coefficients. Thresholds are
      introduced as p values and defined with respect to the physiologic noise
      distribution of the individual maps. Experimental examples from the human visual
      and motor system rely on dynamic acquisitions of gradient-echo echo-planar images
      (2.0 T, TR = 2,000 ms, 96 x 128 matrix) with blood oxygenation level-dependent
      contrast. The results demonstrate the disadvantages of thresholding with fixed
      correlation coefficients. In contrast, taking the individual noise into account
      allows for a derivation of p values and a reliable identification of highly
      significant activation centers. An adequate delineation of the spatial extent of
      activation may be achieved by adding directly neighboring pixels provided their
      correlation coefficients comply with a second lower p value threshold.

PMID- 14725918
TI  - Magnetization transfer MRI of mouse brain reveals areas of high neural density.
AB  - Extending applications of magnetization transfer contrast (MTC) in magnetic
      resonance imaging (MRI) of the human central nervous system, this work
      quantitatively describes MTC of the murine brain. As a novel finding,
      complementing T(1)- and T(2)-weighted MRI, MTC allows for the distinction of
      densely packed gray matter from normal gray and white matter. Examples include
      the Purkinje cell layer and the granular cell layer in the mouse cerebellum as
      well as the delineation of the CA3 subfield of the hippocampus relative to
      surrounding hippocampal gray matter and white matter tracts such as the
      hippocampal fimbria. Using a kainate lesion model, the CA3 hyperintensities in
      MTC and T(1)-weighted MRI are assigned to the densely packed somata of pyramidal
      cells.

PMID- 14725920
TI  - In vivo mapping of functional domains and axonal connectivity in cat visual
      cortex using magnetic resonance imaging.
AB  - Noninvasive cognitive neuroimaging studies based on functional magnetic resonance
      imaging (fMRI) are of ever-increasing importance for basic and clinical
      neurosciences. The explanatory power of fMRI could be greatly expanded, however,
      if the pattern of the neuronal circuitry underlying functional activation could
      be made visible in an equally noninvasive manner. In this study, blood
      oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI)
      were performed in the same cat visual cortex, and the foci of fMRI activation
      utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus
      providing the map of the axonal circuitry underlying visual information
      processing. The methods developed in this study will lay the foundation for in
      vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain
      development.

PMID- 14725921
TI  - Simultaneous acquisition of multiple orders of intermolecular multiple-quantum
      coherence images.
AB  - Recent studies have demonstrated the ability to detect images based on
      intermolecular multiple-quantum coherences (iMQCs) that correspond to flipping of
      two or more separated spins simultaneously, as opposed to conventional magnetic
      resonance where only one spin is flipped at a time. Until now, iMQC imaging has
      only acquired one coherence signal per pulse sequence. Here we report a new
      sequence that successfully detects five orders of coherence (2, 1, 0, -1, and -2
      quantum coherence images) in one pulse sequence, with each signal having its full
      intensity. The simultaneous acquisition highlights substantial contrast
      differences between conventional and iMQC images, and between the different types
      of iMQC images.

PMID- 14725922
TI  - Intermolecular double quantum coherences (iDQc) and diffusion-weighted imaging
      (DWI) imaging of the human brain at 1.5 T.
AB  - To study the sensitivity of intermolecular double quantum coherences (iDQc)
      imaging contrast to brain microstructure and brain anisotropy, we investigated
      the iDQC contrast between differently structured areas of the brain according to
      the strength and the direction of the applied correlation gradient. Thus
      diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) maps have
      been obtained. This procedure, which consists of analyzing both iDQc and DWI
      images at different gradient strength and gradient direction, could be a
      promising tool for clinical brain investigations performed with higher than 1.5 T
      magnetic fields.

PMID- 14725923
TI  - EEG quality during simultaneous functional MRI of interictal epileptiform
      discharges.
AB  - This article concerns the evaluation of the quality of interictal epileptiform
      EEG discharges recorded throughout simultaneous echo planar imaging (EPI). BOLD
      (blood oxygen level dependent) functional MRI (fMRI) images were acquired
      continuously on a patient with intractable epilepsy. EEG was sampled
      simultaneously, during and after imaging, with removal of pulse and imaging
      artifacts by subtraction of channel-specific running averages. Contiguous EEG
      epochs recorded with and without fMRI (fMRI+ve vs. fMRI-ve) were next randomized
      and presented to two blinded observers. Epileptiform discharges were identified
      retrospectively, and comparison was made in terms of the number of identified
      events, their amplitude, and spatiotemporal distribution. A spectral analysis was
      also performed on the EEG. In the randomized comparison of EEG segments, 80
      (fMRI+ve) vs. 69 (fMRI-ve) discharges were noted with good interobserver
      agreement (69%). There were no significant differences in amplitude or spatio
      temporal distribution. Comparison of the events detected and measured by two
      expert observers demonstrated that the Interictal Epileptiform Discharge (IED)
      characteristics were indistinguishable with and without scanning. We review
      briefly the existing literature on EEG recording quality for combined EEG/fMRI.

PMID- 14725924
TI  - Mapping of spikes, slow waves, and motor tasks in a patient with malformation of
      cortical development using simultaneous EEG and fMRI.
AB  - We report on the simultaneous and continuous acquisition of EEG and functional
      MRI data in a patient with a left hemiparesis and focal epilepsy secondary to
      malformation of cortical development in the right hemisphere. EEG-triggered fMRI
      localization was previously demonstrated in this patient. In the experiments
      reported here, 322 spikes maximum at electrode C4 and 126 focal slow waves were
      identified offline. A hierarchy of models was explored in order to assess the
      relative contributions of each type of EEG event. Modeling the BOLD response to
      C4 spikes alone showed an area of activation within the large malformation,
      adjacent to the area of infolding cortex. However, also modeling slow-waves gave
      rise to a broader and stronger activation, suggesting that the generators
      overlap. Motor mapping of the right hand showed activation in the left
      sensorimotor cortex; left-hand tapping led to a more diffuse area of activation,
      displaced superiorly into the superior frontal gyrus, and a small area of
      activation within the lesion. In conclusion, continuous EEG-fMRI is useful to
      compare the functional mapping of epileptiform activity and eloquent cortices in
      individual patients.

PMID- 14725925
TI  - Real-time MR artifacts filtering during continuous EEG/fMRI acquisition.
AB  - The purpose of this study was the development of a real-time filtering procedure
      of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI
      acquisition. The development of a combined EEG and fMRI technique has increased
      in the past few years. Preliminary "spike-triggered" applications have been
      possible because in this method, EEG knowledge was only necessary to identify a
      trigger signal to start a delayed fMRI acquisition. In this way, the two methods
      were used together but in an interleaved manner. In real simultaneous
      applications, like event-related fMRI study, artifacts induced by MRI events on
      EEG traces represent a substantial obstacle for a right analysis. Up until now,
      the methods proposed to solve this problem are mainly based on procedures to
      remove post-processing artifacts without the possibility to control
      electrophysiological behavior of the patient during fMRI scan. Moreover, these
      methods are not characterized by a strong "prior knowledge" of the artifact,
      which is an imperative condition to avoid any loss of information on the
      physiological signals recovered after filtering. In this work, we present a new
      method to perform simultaneous EEG/fMRI study with real-time artifacts filtering
      characterized by a procedure based on a preliminary analytical study of EPI
      sequence parameters-related EEG-artifact shapes. Standard EEG equipment was
      modified in order to work properly during ultra-fast MRI acquisitions. Changes
      included: high-performance acquisition device; electrodes/cap/wires/cables
      materials and geometric design; shielding box for EEG signal receiver; optical
      fiber link; and software. The effects of the RF pulse and time-varying magnetic
      fields were minimized by using a correct head cap wires-locked environment
      montage and then removed during EEG/fMRI acquisition with a subtraction algorithm
      that takes in account the most significant EPI sequence parameters. The on-line
      method also allows a further post-processing utilization.

PMID- 14725926
TI  - Functional MRI using intravascular contrast agents: detrending of the relative
      cerebrovascular (rCBV) time course.
AB  - In pharmacological fMRI experiments in animal models, blood pool contrast agents
      may be used to map cerebral blood volume change as a surrogate for neural
      activation. When the background signal drift due to contrast agent washout is non
      negligible over the duration of the signal changes of interest, time-course
      detrending is essential for accurate interpretation of the experiment. Detrending
      approaches based on estimation of the background signal from a baseline period of
      the time course prior to pharmacological (or functional) challenge were evaluated
      with the aim of identifying a robust method of estimating the contrast agent
      washout contribution to the background signal drift. For fMRI studies in the rat,
      it was found that a constrained fit of a mono-exponential washout model was more
      accurate than a constant background approximation and unconstrained fits for
      experiments investigating the functional response to rapid pharmacological
      challenges such as cocaine and amphetamine. Moreover, the constrained fitting
      approach allows shorter baseline periods than unconstrained extrapolation,
      reducing the required duration of the experiment.

PMID- 14725927
TI  - Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy.
AB  - The aim of our work was to evaluate the feasibility of in vivo single-voxel
      quantitative proton MR spectroscopy in order to identify possible alterations in
      the main metabolite concentrations due to some metabolic dysfunctions in the
      cerebellum of patients suffering from a particular form of migraine called "with
      aura." Measurements of metabolite levels in the cerebellum disclosed reduced
      choline values (normalized both to N-acetyl-aspartate and creatine) in the
      patient group with respect to the age-matched control group. Our interest in this
      pathology is motivated by the fact that there are no available specific
      biochemical markers for migraine characterization, and the current diagnostic
      only takes advantage of the medical history and the clinical examination.

PMID- 14725928
TI  - BOLD signal sign and transient vessels volume variation.
AB  - The purpose of this work was to investigate the relation between BOLD signal sign
      and transient vessels volume variation induced by apnea. This stimulus consisting
      of breath holding after inspiration is able to induce a light slowing down in
      venous blood flow like in a sort of Valsalva maneuver. We observed diffuse
      negative BOLD responding areas at cortical level and a stronger negative response
      in correspondence of the main sinuses. These phenomena seem to be unrelated to a
      specific neural activity, appearing to be expressions of a mechanical variation
      in the hemodynamics. Our study suggests that particular care must be considered
      in the interpretation of fMRI findings, especially when patients with vascular
      related cerebral diseases are involved.

PMID- 14725929
TI  - fMRI of the auditory system: understanding the neural basis of auditory gestalt.
AB  - Functional magnetic resonance imaging (fMRI) has rapidly become the most widely
      used imaging method for studying brain functions in humans. This is a result of
      its extreme flexibility of use and of the astonishingly detailed spatial and
      temporal information it provides. Nevertheless, until very recently, the study of
      the auditory system has progressed at a considerably slower pace compared to
      other functional systems. Several factors have limited fMRI research in the
      auditory field, including some intrinsic features of auditory functional anatomy
      and some peculiar interactions between fMRI technique and audition. A well known
      difficulty arises from the high intensity acoustic noise produced by gradient
      switching in echo-planar imaging (EPI), as well as in other fMRI sequences more
      similar to conventional MR sequences. The acoustic noise interacts in an
      unpredictable way with the experimental stimuli both from a perceptual point of
      view and in the evoked hemodynamics. To overcome this problem, different
      approaches have been proposed recently that generally require careful tailoring
      of the experimental design and the fMRI methodology to the specific requirements
      posed by the auditory research. The novel methodological approaches can make the
      fMRI exploration of auditory processing much easier and more reliable, and thus
      may permit filling the gap with other fields of neuroscience research. As a
      result, some fundamental neural underpinnings of audition are being clarified,
      and the way sound stimuli are integrated in the auditory gestalt are beginning to
      be understood.

PMID- 14725930
TI  - The prospects for high resolution optical brain imaging: the magnetic resonance
      perspective.
AB  - Various analogs of NMR and MRI are now technically possible in optics;
      specifically, high-resolution laser-pulse shaping and complex pulse sequence
      generation with well-defined phase shifts has been demonstrated. Here we
      summarize this technology and discuss the potential for these methods to enhance
      optical functional imaging, competing with (and surpassing?) what is possible by
      functional MRI.

PMID- 14725931
TI  - Applications of laser-polarized 129Xe to biomolecular assays.
AB  - The chemical shift sensitivity and significant signal enhancement afforded by
      laser-polarized 129Xe have motivated the application of 129Xe NMR to biological
      imaging and spectroscopy. Recent research done by our group has used laser
      polarized 129Xe in biomolecular assays that detect ligand-binding events and
      distinguish protein conformations. The successful application of unfunctionalized
      and functionalized 129Xe NMR to in vitro biomolecular assays suggests the
      potential future use of a functionalized xenon biosensor for in vivo imaging.

PMID- 14725932
TI  - Quantitative NumART2* mapping in functional MRI studies at 1.5 T.
AB  - Quantitative mapping of the effective transverse relaxation time, T2* and proton
      density was performed in a motor activation functional MRI (fMRI) study using
      multi-echo, echo planar imaging (EPI) and NumART2* (Numerical Algorithm for Real
      time T2*). Comparisons between NumART2* and conventional single echo EPI with an
      echo time of 64 ms were performed for five healthy participants examined twice.
      Simulations were also performed to address specific issues associated with the
      two techniques, such as echo time-dependent signal variation. While the single
      echo contrast varied with the baseline T2* value, relative changes in T2*
      remained unaffected. Statistical analysis of the T2* maps yielded fMRI activation
      patterns with an improved statistical detection relative to conventional EPI but
      with less activated voxels, suggesting that NumART2* has superior spatial
      specificity. Two effects, inflow and dephasing, that may explain this finding
      were investigated. Particularly, a statistically significant increase in proton
      density was found in a brain area that was detected as activated by conventional
      EPI but not by NumART2* while no such changes were observed in brain areas that
      showed stimulus correlated signal changes on T2* maps.

PMID- 14725933
TI  - Investigating directed cortical interactions in time-resolved fMRI data using
      vector autoregressive modeling and Granger causality mapping.
AB  - We present a framework aimed to reveal directed interactions of activated brain
      areas using time-resolved fMRI and vector autoregressive (VAR) modeling in the
      context of Granger causality. After describing the underlying mathematical
      concepts, we present simulations helping to characterize the conditions under
      which VAR modeling and Granger causality can reveal directed interactions from
      fluctuations in BOLD-like signal time courses. We apply the proposed approach to
      a dynamic sensorimotor mapping paradigm. In an event-related fMRI experiment,
      subjects performed a visuomotor mapping task for which the mapping of two stimuli
      ("faces" vs "houses") to two responses ("left" or "right") alternated
      periodically between the two possible mappings. Besides expected activity in
      sensory and motor areas, a fronto-parietal network was found to be active during
      presentation of a cue indicating a change in the stimulus-response (S-R) mapping.
      The observed network includes the superior parietal lobule and premotor areas.
      These areas might be involved in setting up and maintaining stimulus-response
      associations. The Granger causality analysis revealed a directed influence
      exerted by the left lateral prefrontal cortex and premotor areas on the left
      posterior parietal cortex.

PMID- 14725934
TI  - Ultrahigh field magnetic resonance imaging and spectroscopy.

PMID- 14725935
TI  - The physiology and metabolism of neuronal activation: in vivo studies by NMR and
      other methods.
AB  - In this article, a review is made of the current knowledge concerning the
      physiology and metabolism of neuronal activity, as provided by the application of
      NMR approaches in vivo. The evidence furnished by other functional spectroscopic
      and imaging techniques, such as PET and optical methods, are also discussed. In
      spite of considerable amounts of studies presented in the literature, several
      controversies concerning the mechanisms underlying brain function still remain,
      mainly due to the difficult assessment of the single vascular and metabolic
      dynamics which generally influence the functional signals. In this framework,
      methodological and technical improvements are required to provide new and
      reliable experimental elements, which can support or eventually modify the
      current models of activation.

PMID- 14725936
TI  - In vivo 1H NMR spectroscopy of individual human brain metabolites at moderate
      field strengths.
AB  - This article reviews spectral editing techniques for in vivo 1H NMR spectroscopy
      of human brain tissue at moderate field strengths of 1.5-3 Tesla. Various aspects
      of 1H NMR spectroscopy are discussed with regard to in vivo applications. The
      parameter set [delta, J, n] (delta being the relative chemical shift, J the
      scalar coupling constant and n the number of coupled spins) is used to
      characterize the spin systems under investigation and to classify the editing
      techniques that are used in in vivo 1H NMR spectroscopy.

PMID- 14725937
TI  - Reference methods for the measurement of free thyroid hormones in blood:
      evaluation of potential reference methods for free thyroxine.
AB  - In this paper, a review of the literature on the methods for the detection of
      FT(4) is provided. Furthermore, an overview of the most important uncertainties
      and interferences of the potential reference methods for determination of free
      thyroxine (free triiodothyronine) are also presented. Especially, the separation
      step-dialysis, or ultrafiltration-implies important technical and theoretical
      uncertainties and interferences as to the methods.Furthermore, a short review of
      methods based on isotope dilution/mass spectrometry (ID/MS) to quantify thyroxine
      is provided. There has so far been no attempt to quantify the free fraction of
      thyroxine by ID/MS, probably due to lack of sensitivity, but if quantification of
      the free fraction of thyroxine can be done with ID/MS, then this step seems the
      least compromised step only including minor uncertainties in comparison to the
      separation step.

PMID- 14725938
TI  - Relationship between plasma Cystatin C and creatinine in chronic renal diseases
      and Tx-transplant patients.
AB  - OBJECTIVES: Glomerular filtration rate (GFR) is the best overall index of renal
      function in health and disease. Recently, Cystatin C (Cyst C), a low molecular
      weight protein freely filtered through the glomerulus, and almost completely
      reabsorbed and catabolized by tubular cells, has been proposed as a new and very
      sensitive serum marker of change in GFR. This study investigated the relationship
      between Cyst C and creatinine (CR) in renal disease patients. METHODS: Serum Cyst
      C was determined by particle-enhanced immunoturbidimetry using the Cyst C PET
      kit. The results could be obtained within 1 h. Cuvettes were washed before the
      Cyst C assay as recommended. Serum CR, BUN and albumin were determined by auto
      analyzer. RESULTS: A strong correlation was observed between Cyst C and CR (P =
      0.001, r = 0.764 and P = 0.0001, r = 0.888, respectively) in prehemodialysis (pre
      HD) and kidney transplantation (Tx-kidney), whereas there was a weak correlation
      in continuous ambulatory peritoneal dialysis (CAPD) (P = 0.05, r = 0.535).
      CONCLUSION: These findings suggest that serum Cyst C may be considered as a
      sensitive predictive parameter for reduced GFR. It is of value for the laboratory
      diagnosis of chronic renal failure and should be preferentially used for CR
      clearance.

PMID- 14725939
TI  - Association of a salivary acetylcholinesterase with Alzheimer's disease and
      response to cholinesterase inhibitors.
AB  - OBJECTIVES: A decrease in cholinergic activity is a key event in the biochemistry
      of Alzheimer's disease (AD). The aim of the study was to investigate the
      expression levels of markers of cholinergic function in saliva, which is a
      readily accessible body fluid that can be obtained from subjects with minimal
      distress. DESIGN AND METHODS: Salivary samples were obtained from people with
      NINCDS-ARDRA "probable" Alzheimer's disease and age- and sex-matched controls.
      Salivary acetylcholinesterase enzyme (AChE) activity was determined
      colorometrically. RESULTS: Robust AChE catalytic activity was detected in the
      saliva samples that was stable for up to 6 h at room temperature following the
      provision of the salivary sample. The activity of the enzyme was significantly
      lower in people with AD than in age-matched controls. In addition, there were
      significant differences in activity between those who responded to
      acetylcholinesterase inhibitor (AChE-I) therapy and those who did not.
      CONCLUSIONS: Salivary enzyme activity may therefore prove to be a useful marker
      of central cholinergic activity.

PMID- 14725940
TI  - Differences in urinary albumin detected by four immunoassays and high-performance
      liquid chromatography.
AB  - OBJECTIVES: To compare the analysis of urinary albumin from diabetic patients by
      four conventional immunoassays including radioimmunoassay (RIA),
      immunonephelometry (IN), and two different methods of immunoturbidimetry (IT), as
      well as by high-performance liquid chromatography (HPLC). DESIGN AND METHODS:
      Urines were collected over a 24-h period and stored at -20 degrees C until assay.
      Urinary albumin concentration was determined by an in-house RIA, by IN using a
      Beckman Array Analyser with reagents from Beckman Diagnostics (Sydney,
      Australia), by IT using a Dade-Behring Turbitimer with reagents from Dade-Behring
      (Marburg, Germany), by IT using a Dade-Behring Dimension R x L Chemistry Analyser
      with reagents from DiaSorin (Stillwater, OK, USA), and by HPLC using a Zorbax Bio
      series preparative GF-250 column. Regression lines were calculated using a least
      squares method to determine the correlation between the assays studied. Bland
      Altman bias plots including limits of agreement were also calculated. RESULTS:
      The correlation coefficients calculated were high (>0.85) indicating a strong
      linear relationship between all assays studied. The slopes calculated for the
      comparisons demonstrate that each assay can vary from one another (up to
      threefold) and have a slope significantly different from an ideal slope of 1 (P <
      0.001). These results were confirmed by Bland-Altman bias plots and calculation
      of the limits of agreement that were all large. CONCLUSIONS: At this time, there
      is no global standard by which urinary albumin assays may be standardized. This
      study suggests the need for such standards.

PMID- 14725941
TI  - A novel automated method to measure total antioxidant response against potent
      free radical reactions.
AB  - OBJECTIVES: Oxidative damage of biomolecules occurs as a result of potent free
      radical reactions. In this study, a novel, colorimetric and fully automated
      method for measuring total antioxidant response (TAR) against potent free radical
      reactions is described. DESIGN AND METHODS: Potent free radical reactions were
      initiated with the production of hydroxyl radical (OH(*)) via Fenton reaction,
      and the rate of the reactions was monitored by following the absorbance of
      colored dianisidyl radicals. Ortho-dianisidine (10 mM) and ferrous ammonium
      sulfate (45 microM) were dissolved in KCl/HCl solution (75 mM, pH 1.8). This
      mixture was named as Reagent 1 and hydrogen peroxide solution (7.5 mM) as Reagent
      2. The OH(*), produced by mixing of R1 and R2, oxidized o-dianisidine molecules
      into dianisidyl radicals, leading to a bright yellow-brown color development
      within seconds. Antioxidants, present in the sample, suppressed the color
      formation to a degree that is proportional to their concentrations. The method
      was applied to an automated analyzer and analytical performance characteristics
      of the assay were determined. RESULTS: Vitamin C and Trolox, reduced glutathione,
      bilirubin, uric acid and (+/-)-catechin solutions suppressed the color formation
      depending on their concentrations. Serum TAR against potent free radical
      reactions was lower in patients with chronic renal failure (1.13 +/- 0.21 mmol
      Trolox equiv./l) and was higher in the individuals with neonatal icterus (2.82 +/
      1.18 mmol Trolox equiv./l) than in healthy subjects (1.54 +/- 0.15 mmol Trolox
      equiv./l). CONCLUSIONS: The easy, inexpensive and fully automated method
      described can be used to measure TAR of samples against potent free radical
      reactions.

PMID- 14725942
TI  - Kinetic studies of the interaction between antitumor antibiotics and DNA using
      quartz crystal microbalance.
AB  - OBJECTIVE: Kinetic studies of the interaction process between antitumor
      antibiotics, Mitomycin C (MMC) and Bleomycin (BLM), and DNA were performed with a
      novel analytical method, piezoelectric quartz crystal (PQC) impedance analysis.
      DESIGN AND METHODS: DNA was directly immobilized on the Au-electrode surface of a
      piezoelectric quartz crystal by adsorption. The DNA-modified piezoelectric sensor
      was in contact with Mitomycin C and Bleomycin solution, respectively. RESULTS:
      The experimental results demonstrated that antitumor antibiotics concentration
      had an effect on the interaction. A pseudo-first-order kinetic model for the
      interaction between antitumor antibiotics and DNA was derived to describe the
      process. All fitted results were well in agreement with the corresponding
      experimental results. The kinetic parameters, the interaction rate constants
      (k(MMC) and k(BLM)), were determined by fitting experimental data to the model.
      At 37 +/- 0.5 degrees C, the k(MMC) and k(BLM) values obtained were 4.56 (+/
      0.02) x 10(-3) and 9.11 (+/-0.02) mM(-1) s(-1), respectively. CONCLUSION:
      Piezoelectric quartz crystal impedance (PQCI) analysis is a very powerful method
      to study the kinetic process of antitumor drugs and DNA interaction.

PMID- 14725943
TI  - Population-based differences in frequency of the transcobalamin II Pro259Arg
      polymorphism.
AB  - OBJECTIVE: A common polymorphism of the transcobalamin II (TC-II) gene,
      Pro250Arg, has been implicated as a possible genetic factor in population-based
      differences in vitamin B(12) metabolism. Our objective was to determine whether
      the prevalence of TC-II Pro259Arg polymorphism differs significantly between
      Caucasian, Asian and African-American groups. METHODS: Genomic DNA was available
      on 187 Caucasians and 43 Asians from the Toronto area, and 51 African-Americans
      from Northeastern United States. A mutagenically separated PCR method was
      employed to genotype these groups for the TC-II Pro259Arg polymorphism (776C-
      >G). RESULTS: The frequency of the Arg 259 allele varied significantly among the
      three groups studied (0.439 in Caucasian, 0.558 in Asian and 0.363 in African; P
      = 0.022). The Asian group had a significantly higher frequency of the Arg 259
      allele compared to the Caucasian (P = 0.030) and the African-American group (P =
      0.006). The frequency of the Arg 259 allele in the Caucasian and African-American
      groups was not significantly different (P = 0.103). CONCLUSION: Population-based
      differences in TC-II Pro259Arg frequency are significant and could be a
      contributor to ethnic variation in susceptibility to vitamin B(12) deficiency, a
      common and persistent problem.

PMID- 14725944
TI  - S100B content and SOD activity in amniotic fluid of pregnancies with Down
      syndrome.
AB  - OBJECTIVES: We measured S100B levels and superoxide dismutase (SOD) activity
      retrospectively in amniotic fluid samples from pregnancies with normal and Down
      syndrome (DS) fetuses. DESIGN AND METHODS: Samples from 26 normal and 71 Down
      syndrome fetuses were studied. S100B protein levels were determined using LIA-mat
      Sangtec kit, and SOD activity was measured with the RANSOD kit. RESULTS: We
      observed significantly higher levels of S100B in the Down group (median of 1.24
      microg/l) than in the control group (median 0.69 microg/l). S100B concentration
      in DS samples increased from the 13th to the 18th week of gestation and was
      positively correlated with gestational age. The amniotic fluid SOD activity in
      the DS group (16.60 U/mg/prot) was significantly higher than in the normal one
      (10.78 U/mg/prot). CONCLUSIONS: This study indicates that S100B and SOD in
      amniotic fluid could be used as additional parameters for prenatal screening of
      trissomy 21 and that S100B values are associated with the gestational age.

PMID- 14725945
TI  - Effect of Agkistroden blomhoffi (mamushi) on the proliferation of human
      fibroblasts.
AB  - OBJECTIVES: The purpose of this study is to investigate the effect of Agkistroden
      blomhoffi (mamushi) aqueous extract on human patellar tendon cells in vitro, to
      pharmacologically explain the natural medicine's healing effect on tendon, bone
      and muscle injuries. DESIGN AND METHODS: Human patellar tendon fibroblasts (HPTF)
      were incubated in media containing different concentrations of mamushi aqueous
      extract. Cell proliferation was studied by microscopic observations and total
      protein, actin, collagen I, and cyclooxygenase-2 (Cox 2) expressions. RESULTS:
      Mamushi aqueous extract enhanced HPTF proliferation when its concentration was
      lower than 333 microg/ml. Cells cultured in manushi-containing medium showed
      developed intercellular structure and increased protein production. However,
      mamushi extract higher than 500 microg/ml oppressed cell growth. At 667
      microg/ml, mamushi induced Cox 2 production, a sign of cytotoxicity. CONCLUSION:
      A. blomhoffi aqueous extract was found to directly stimulate the proliferation
      and protein production, particularly collagen I synthesis, of HPTF in a dose
      dependent manner.

PMID- 14725946
TI  - Decreased adrenomedullin and total nitrite levels in breast milk of preeclamptic
      women.
AB  - OBJECTIVE: To observe the adrenomedullin (AM) and total nitrite levels in the
      milk of preeclamptic and normal pregnant women. DESIGN AND METHODS: Fifteen women
      with preeclampsia and 15 normal pregnant women were included in the study. Total
      nitrite was quantitated by Griess reaction, while AM was measured by HPLC.
      RESULTS: The levels of AM and total nitrite in colostrum and 30th-day breast milk
      were decreased in preeclamptics. Total nitrite levels (micromol/l) were 56.09 +/-
      11.18 vs. 82.20 +/- 12.01, P < 0.05, in colostrum of preeclamptics and controls,
      respectively. The level of total nitrite was 37.75 +/- 12.10 vs. 53.28 +/- 10.25,
      P < 0.05, in 30th-day milk of same patients. AM levels (pg/ml) were 11.18 +/-
      1.11 vs. 16.59 +/- 1.24, P < 0.0001, in colostrum of preeclamptics and controls,
      respectively. In 30th-day milk of same patients, AM levels were 8.41 +/- 1.39 vs.
      12.18 +/- 1.48, P < 0.005, respectively. CONCLUSION: This report shows for the
      first time that human milk has decreased levels of AM and total nitrite in
      preeclampsia.

PMID- 14725947
TI  - Distribution of plasma total homocysteine concentrations in the healthy Iranians.
AB  - OBJECTIVE: The distribution of plasma total homocysteine concentrations in a
      population of South West of Iran Shiraz is described to test for differences in
      homocysteine concentrations among gender and age groups and those levels reported
      in other populations. DESIGN AND METHODS: Two hundred one healthy males and 201
      healthy females aged >15 years from Shiraz, Iran, were randomly selected. Plasma
      total homocysteine concentrations were measured using high-performance liquid
      chromatography. RESULTS: The mean plasma homocysteine level was significantly
      higher in men (geometric mean, 7.3 micromol/l) than in women (geometric mean, 6.3
      micromol/l, P < 0.001). The geometric mean levels for ages 15-25, 26-36, 37-47,
      and 48-58, 59-69, and 70-80 years, were 5.9, 5.4, 5.2, 6.7, 7.3, and 7.6
      micromol/l in women and 7.5, 8.7, 5.9, 5.9,7.2, and 9.1 micromol/l in men,
      respectively. CONCLUSIONS: The homocysteine distribution in a representative
      sample of people of southwest of Iran indicates age and gender differences, as is
      found in other populations.

PMID- 14725948
TI  - Measurement of inaccuracy and imprecision of HCG methods using dilutions of the
      WHO 4th IS-HCG standard and a pregnant patient's serum.
AB  - INTRODUCTION: Differences in human chorionic gonadotropin (hCG) results obtained
      by seven different methods were documented by analyzing dilutions of the WHO 4th
      International Standard (IS) and a pregnant patient's serum. MATERIALS AND
      METHODS: Biases of +30.9 to -37.5% and +36.8 to -36.1% from the target
      concentration were found for the WHO 4th IS and patient sample dilutions,
      respectively. RESULTS: Imprecision was calculated from replicate measurements of
      hCG on the different sample dilutions. Imprecision ranged from 1.0% to 18.9% and
      1.1% to 5.3% for the WHO 4th IS and patient sample dilutions, respectively. Using
      a maximum allowable error of 12.5% for hCG measurements, we found that two
      instruments were so biased that their hCG measurements could not be interchanged
      with hCG values produced by any of the other systems. DISCUSSION: It is ideal to
      use only one hCG methodology for the serial monitoring of hCG; otherwise, hCG
      methods should be carefully chosen to minimize inter-method bias.

PMID- 14725949
TI  - Polyelectrolyte-stabilized glucose biosensor based on woodceramics as electrode.
AB  - OBJECTIVE: Different biosensors for early diagnosis of diabetes have been
      discussed increasingly. We demonstrate the applicability of a glucose biosensor
      for rapid and quantitative determination of glucose in experimental sample
      solutions. DESIGN AND METHODS: Polyethylenimine (PEI)-stabilized glucose oxidase
      (GOD) was used for the construction of stable glucose biosensor utilizing a
      simple manufacture procedure. The stabilized glucose oxidase was immobilized by
      physical adsorption into activated porous and conductive carbonaceous material
      woodceramics that served as the immobilization matrix and the electrochemical
      transducer. The optimum parameters for the construction of the biosensor and the
      influences of pH and temperature on the biosensor response were explored.
      RESULTS: Optimum results were obtained using soaking solutions of 2300 U/ml GOD,
      10 mg/ml mediator toluidine blue O (TBO), and 2.0%, w/v PEI. The sensitivity of
      the resulting biosensor for glucose was 1.22 microA/mM, with a linear response in
      the concentration range of 0.5-7 mM. The sensor-to-sensor reproducibility was
      good, the relative standard deviation (R.S.D.) being less than 8.0%. The storage
      and operational stabilities of the glucose biosensor were good. CONCLUSIONS: The
      glucose biosensor provides reproducible and quantitative information on glucose
      within minutes and is applicable for the detection of glucose in experimental
      samples.

PMID- 14725950
TI  - Dose related risk of motor vehicle crashes after cannabis use.
AB  - The role of Delta(9)-tetrahydrocannabinol (THC) in driver impairment and motor
      vehicle crashes has traditionally been established in experimental and
      epidemiological studies. Experimental studies have repeatedly shown that THC
      impairs cognition, psychomotor function and actual driving performance in a dose
      related manner. The degree of performance impairment observed in experimental
      studies after doses up to 300 microg/kg THC were equivalent to the impairing
      effect of an alcohol dose producing a blood alcohol concentration (BAC) >/=0.05
      g/dl, the legal limit for driving under the influence in most European countries.
      Higher doses of THC, i.e. >300 microg/kg THC have not been systematically studied
      but can be predicted to produce even larger impairment. Detrimental effects of
      THC were more prominent in certain driving tasks than others. Highly automated
      behaviors, such as road tracking control, were more affected by THC as compared
      to more complex driving tasks requiring conscious control. Epidemiological
      findings on the role of THC in vehicle crashes have sometimes contrasted findings
      from experimental research. Case-control studies generally confirmed experimental
      data, but culpability surveys showed little evidence that crashed drivers who
      only used cannabis are more likely to cause accidents than drug free drivers.
      However, most culpability surveys have established cannabis use among crashed
      drivers by determining the presence of an inactive metabolite of THC in blood or
      urine that can be detected for days after smoking and can only be taken as
      evidence for past use of cannabis. Surveys that established recent use of
      cannabis by directly measuring THC in blood showed that THC positives,
      particularly at higher doses, are about three to seven times more likely to be
      responsible for their crash as compared to drivers that had not used drugs or
      alcohol. Together these epidemiological data suggests that recent use of cannabis
      may increase crash risk, whereas past use of cannabis does not. Experimental and
      epidemiological research provided similar findings concerning the combined use of
      THC and alcohol in traffic. Combined use of THC and alcohol produced severe
      impairment of cognitive, psychomotor, and actual driving performance in
      experimental studies and sharply increased the crash risk in epidemiological
      analyses.

PMID- 14725951
TI  - Neurobehavior disinhibition in childhood predisposes boys to substance use
      disorder by young adulthood: direct and mediated etiologic pathways.
AB  - OBJECTIVE: The development of substance use disorder (SUD) was prospectively
      investigated in 66 boys having fathers with SUD and 104 boys having fathers with
      no adult Axis I or II psychiatric disorder. Evaluations were conducted to
      determine the context in which neurobehavior disinhibition in relation to
      parental SUD, parental neglect of the child and child's social maladjustment
      culminated in a DSM-III-R diagnosis of SUD. METHODS: A neurobehavior
      disinhibition latent trait was derived using indicators of behavior undercontrol,
      affect dysregulation and executive cognitive functioning in the boys when they
      were 10-12 and again at 16 years of age. These latter characteristics have been
      frequently observed in individuals who have a prefrontal cortex disturbance. The
      data were analyzed to determine whether the score on the neurobehavior
      disinhibition construct mediates the association between father's and mother's
      SUD and son's SUD. RESULTS: SUD in the mother and father predicted neurobehavior
      disinhibition in the son. The neurobehavior disinhibition score in the sons
      predicted SUD between ages 10-12 and 19. Neurobehavior disinhibition, in
      conjunction with social maladjustment and drug use frequency, mediated the
      association between paternal and maternal SUD and son's SUD. Neurobehavior
      disinhibition was unrelated to neglect of the child by either the father or
      mother; however, paternal but not maternal neglect at age 10-12 predicted SUD at
      age 19. CONCLUSIONS: The association of neurobehavior disinhibition in childhood
      and SUD by young adulthood suggests that a prefrontal cortex dysfunction
      contributes to SUD liability. The results extend previous findings demonstrating
      that neurobehavior disinhibition is an important component of the liability to
      SUD.

PMID- 14725952
TI  - Characterizing the subjective, psychomotor, and physiological effects of oral
      propoxyphene in non-drug-abusing volunteers.
AB  - BACKGROUND: The subjective, psychomotor, and physiological effects of a widely
      prescribed prescription opioid, propoxyphene, have not been studied in a
      population of non-drug-abusing people. The drug also has potential for abuse and
      it was of interest in the present study to determine if the drug had any abuse
      liability-related subjective effects in this population. METHODS: Eighteen
      volunteers participated in a crossover, randomized, double-blind study in which
      they received, all p.o., placebo; 50 mg propoxyphene napsylate; 100 mg
      propoxyphene napsylate; 200 mg propoxyphene napsylate; 40 mg morphine sulfate;
      and 2 mg lorazepam. Measures were assessed before and for 300 min after drug
      administration. RESULTS: Both morphine and lorazepam produced subjective effects.
      There were no statistically significant subjective effects obtained with any dose
      of propoxyphene in the group as a whole, but approximately 30-50% of the subjects
      did appear to experience subjective effects from the drug. Drug liking was not
      consistently observed in this subset. Propoxyphene, unlike lorazepam, did not
      impair psychomotor or cognitive performance. Both propoxyphene and morphine
      produced miosis. CONCLUSIONS: There was a lack of statistically significant
      subjective effects of propoxyphene in the group as a whole, including a
      propoxyphene dose that was twice as high as the typical clinically-prescribed
      dose of 100 mg. However, there were some subjects who did report effects,
      consistent with the notion that patients differ in their sensitivity to opioid
      effects.

PMID- 14725953
TI  - Comparison of self-report versus agency records of service utilization in a
      community sample of individuals with alcohol use disorders.
AB  - Health services research has become an important area for evaluating the cost
      effectiveness of interventions. When used in treatment outcome research, the
      accuracy of self-report data is essential. The reliability and validity of self
      report service utilization among alcohol and drug addicted individuals is
      questionable and largely unexplored. This study assessed the accuracy of self
      report utilization of services compared to service record abstraction in a sample
      of treatment seeking individuals with alcohol use disorders. The results of the
      comparative analysis found that the level of agreement for some services,
      particularly medical, psychiatric and substance abuse inpatient admissions, and
      social service involvement was good. There was less agreement in emergency room
      visits and arrests. Factors related to discrepancies between self-report and
      records were explored.

PMID- 14725954
TI  - Developmentally inspired drug prevention: middle school outcomes in a school
      based randomized prevention trial.
AB  - Prior investigations have linked behavioral competencies in primary school to a
      reduced risk of later drug involvement. In this randomized prevention trial, we
      sought to quantify the potential early impact of two developmentally inspired
      universal preventive interventions on the risk of early-onset alcohol, inhalant,
      tobacco, and illegal drug use through early adolescence. Participants were
      recruited as they entered first grade within nine schools of an urban public
      school system. Approximately, 80% of the sample was followed from first to eighth
      grades. Two theory-based preventive interventions, (1) a family-school
      partnership (FSP) intervention and (2) a classroom-centered (CC) intervention,
      were developed to improve early risk behaviors in primary school. Generalized
      estimating equations (GEE) multivariate response profile regressions were used to
      estimate the relative profiles of drug involvement for intervention youths versus
      controls, i.e. youth in the standard educational setting. Relative to control
      youths, intervention youths were less likely to use tobacco, with modestly
      stronger evidence of protection associated with the CC intervention (RR=0.5;
      P=0.008) as compared to protection associated with the FSP intervention (RR=0.6;
      P=0.042). Intervention status was not associated with risk of starting alcohol,
      inhalants, or marijuana use, but assignment to the CC intervention was associated
      with reduced risk of starting to use other illegal drugs by early adolescence,
      i.e. heroin, crack, and cocaine powder (RR=0.32, P=0.042). This study adds new
      evidence on intervention-associated reduced risk of starting illegal drug use. In
      the context of 'gateway' models, the null evidence on marijuana is intriguing and
      merits attention in future investigations.

PMID- 14725955
TI  - Inconsistent condom use among HIV-infected patients with alcohol problems.
AB  - BACKGROUND: Unsafe sexual behavior is common among persons with negative or
      unknown HIV status and it is augmented by alcohol use in some populations. We
      examined the association between alcohol consumption level (abstinent, moderate,
      at-risk) and inconsistent condom use in a cohort of HIV-infected individuals with
      a history of alcohol problems. METHODS: Subjects (n=345) had up to seven
      structured interviews over 36 months. Identical questions on alcohol consumption
      and inconsistent condom use were asked at each interview. We used generalized
      estimating equations (GEE) multivariate logistic regression for repeated
      measurements analysis. We adjusted for potential confounding factors and explored
      possible interactions. RESULTS: At baseline, 132 (38%) participants reported
      inconsistent condom use. We detected a significant (P=0.0002) interaction between
      alcohol consumption and injection drug use (IDU) variables. Among active
      injection drug users, at-risk drinking was associated with inconsistent condom
      use, adjusted odds ratio (OR; 95% confidence interval) 4.3 (1.5, 12.2). Among
      those who did not inject drugs, at-risk drinking and inconsistent condom use were
      not associated, 0.7 (0.4, 1.3). Inconsistent condom use was more common among
      women, those believing condoms to be 'a hassle', and persons living with a
      partner. CONCLUSION: In HIV-infected drug-injecting individuals, excessive use of
      alcohol is associated with unsafe sexual practices.

PMID- 14725956
TI  - An association between smoking habits and blood pressure in normotensive Japanese
      men: a 5-year follow-up study.
AB  - BACKGROUND: There are few studies on the effects of smoking on blood pressure
      (BP) that consider confounding factors such as age, obesity, lifestyle and blood
      chemistry. As such, we conducted a 5-year follow-up study to clarify the effects
      of smoking habits on blood pressure in normotensive Japanese men. METHODS: The
      subjects were 2107 normotensive male steelworkers aged 40-54 years. They were
      classified using three indices: smoking habits in 1990, changes in smoking
      habits, and changes in amount of smoking. The associations between these indices
      and changes in blood pressure were evaluated using analysis of covariance
      (ANCOVA). As analyses, BMI, salt intake, physical activity, drinking habit, and
      results of blood chemistry in 1990 and their changes, age and blood pressure in
      1990 were used as covariates. RESULTS: The cumulative incidence of hypertension
      in smokers was lower than in non- and ex-smokers. The adjusted mean of change in
      blood pressure of smokers was significantly lower than in non- and ex-smokers. No
      significant difference between non-smokers and ex-smokers, or among groups of
      smokers who varied their amount of smoking was observed. CONCLUSION: Chronic
      smoking reduces changes in blood pressure and 5-year cumulative incidence of
      hypertension. However, no significant dose-dependent effect of smoking on changes
      in blood pressure was observed.

PMID- 14725957
TI  - Personality profile and drug of choice; a multivariate analysis using Cloninger's
      TCI on heroin addicts, alcoholics, and a random population group.
AB  - As personality may predispose, precipitate or perpetuate substance abuse and/or
      dependence, and as it is considered to remain stable across the years in a given
      subject, potential links with the drug of choice may help screen future patients
      before drug consumption. The present study compared three groups: 42 patients
      with heroin dependence (mean age: 31.2; standard deviation (SD): 5.5; 10
      females), 37 patients with alcohol dependence (mean age 44.2; SD: 9.1; 9 females)
      and 83 subjects from a random population sample (mean age: 38.8; SD: 6.9; 20
      females). Personality was measured by Cloninger's Temperament and Character
      Inventory (TCI). Pillai's MANCOVA with age as a covariate and gender as a
      cofactor was highly significant. Univariate ANOVA analyses using TCI dimensions
      as dependent variable showed most variables to vary in parallel for the two
      patient groups in comparison with controls. Post-hoc tests showed heroin patients
      to score higher in Novelty-Seeking and Self-Directedness than alcohol patients.
      Sub-dimensions Exploratory Excitability, Fear of the Uncertain, Responsibility,
      Congruent Second Nature and Transpersonal Identification were also significantly
      different in the two patient samples. Logistic regression showed Exploratory
      Excitability to segregate up to 76% of heroin patients from alcohol patients. In
      conclusion, personality profiles were linked to some preferential choice of drug
      and personality screening might be tested in preventive strategies.

PMID- 14725958
TI  - Neurological and cognitive impairment associated with leaded gasoline
      encephalopathy.
AB  - BACKGROUND: A toxic encephalopathy (or 'lead encephalopathy') may arise from
      leaded gasoline abuse that is characterised by tremor, hallucinations, nystagmus,
      ataxia, seizures and death. This syndrome requires emergency and intensive
      hospital treatment. METHODS: We compared neurological and cognitive function
      between chronic gasoline abusers with (n=15) and without (n=15) a history of
      leaded gasoline encephalopathy, and with controls who had never abused gasoline
      (n=15). RESULTS: Both groups of chronic gasoline abusers had abused gasoline for
      the same length of time and compared to controls, showed equivalently elevated
      blood lead levels and cognitive abnormalities in the areas of visuo-spatial
      attention, recognition memory and paired associate learning. However, where
      gasoline abusers with no history of leaded gasoline encephalopathy showed only
      mild movement abnormalities, gasoline abusers with a history of leaded gasoline
      encephalopathy showed severe neurological impairment that manifest as higher
      rates of gait ataxia, abnormal rapid finger tapping, finger to nose movements,
      dysdiadochokinesia and heel to knee movements, increased deep tendon reflexes and
      presence of a palmomental reflex. CONCLUSIONS: While neurological and cognitive
      functions are disrupted by chronic gasoline abuse, leaded gasoline encephalopathy
      is associated with additional and long-lasting damage to cortical and cerebellar
      functions.

PMID- 14725959
TI  - Adapting the Illicit Drug Reporting System (IDRS) to examine the feasibility of
      monitoring trends in the markets for 'party drugs'.
AB  - Since 1996, the Illicit Drug Reporting System (IDRS), Australia's strategic early
      warning system for illicit drug trends, has monitored annual trends in the
      markets for the four main illicit drug classes, cannabis, methamphetamine,
      cocaine and heroin. In 2000, a 2-year trial was implemented to examine the
      feasibility of using similar methodology to monitor trends in the markets for
      'party drugs'. A triangulation of three data sources was sought: (1) quantitative
      interviews with a 'sentinel' population of drug users; (2) qualitative interviews
      with key informants (KIs), or those who have contact with drug users through
      their work; (3) extant indicator data sources such as the purity of illicit drugs
      seized by law enforcement agencies. The results suggested that the feasibility of
      collecting detailed, reliable and valid data about party drug markets is a direct
      function of the size of those markets. The trial demonstrated that the system
      would allow the successful monitoring of markets for party drugs that are
      relatively widely used, such as ecstasy, but would be less sensitive in
      monitoring markets for party drugs that are used by small proportions of the
      total population, such as gamma-hydroxy-butyrate (GHB) and ketamine.
      Methodological issues encountered during the conduct of this trial are discussed,
      including defining the appropriate sentinel population of drug users, identifying
      relevant key informants, and the relative absence of extant indicator data
      sources that could inform our understanding of party drug markets.

PMID- 14725960
TI  - Prescription opioid abuse in patients presenting for methadone maintenance
      treatment.
AB  - To characterize prescription opioid dependent patients in a methadone maintenance
      treatment (MMT) program, a detailed retrospective chart review of new admissions
      (1997-1999, n=178, mean age=34.5+/-0.7 years, 65% male) was conducted. At
      admission most patients (83%) had been using prescription opioids (+/-heroin).
      Four groups were identified: 24% had used prescription opioids only; 24% used
      prescription opioids initially and heroin later; 35% used heroin first and
      prescription opioids subsequently; and 17% had used heroin only (this group was
      significantly younger: mean age 26+/-1 years, P=0.0001). Subjects reported
      regular use of prescription opioids at higher than therapeutic dosages. For
      example, in the 'prescription opioid only' group the reported mean (+/-S.E.)
      number of codeine or oxycodone-containing tablets consumed daily was 23 (+/-6)
      tablets and 21 (+/-3) tablets, respectively. There were no significant
      differences found amongst the groups in measures of social stability. Those
      dependent on prescription opioids alone were less likely to use illicit non
      opioid drugs or to be associated with injection drug use. Those that used
      prescription opioids only or initially were more likely to have ongoing pain
      problems and to be involved in psychiatric treatment. Further research is
      required to better elucidate the complex relationships between pain, mental
      health and addiction in order to develop optimal prevention and treatment
      strategies for prescription opioid dependence.

PMID- 14725961
TI  - Smoking cessation efforts among substance abusing adolescents.
AB  - Available research demonstrates that substance abusing youth are heavy cigarette
      smokers for whom the behavior persists into adulthood. As such this population
      represents an important target for intervention. In order to inform treatment
      design, the present paper described cessation efforts, including motives and
      methods for quitting, in a sample of cigarette smoking adolescents who received
      inpatient or outpatient treatment for substance abuse. The 183 participants were
      on average 16.2 years old, 45% were females, and 72% were white. Consistent with
      studies of community and high risk youth samples, the majority of participants
      had previously attempted cessation, yet reported little success in maintaining
      abstinence. Health emerged as a frequently endorsed motive for cessation and
      stopping abruptly (cold turkey) was the most commonly reported strategy for
      quitting.

PMID- 14725962
TI  - Comparison between the influence of shocks and endotoxemia on the activation of
      brain cells that contain nitric oxide.
AB  - We sought to identify the brain circuitry that underlies the stimulatory role of
      nitric oxide (NO) role on the hypothalamic-pituitary-adrenal (HPA) axis.
      Specifically, we determined whether electrofootshocks (60 min) or the intravenous
      administration of lipopolysaccharide (LPS, 100 microg/kg)-activated
      neurocircuitries that express either neuronal NO synthase (nNOS), a constitutive
      enzyme responsible for NO formation, or L-citrulline, an amino acid that is
      produced in equimolar amounts with NO. Shocks significantly increased the number
      of cells showing Fos immunoreactivity (ir) in the paraventricular nucleus (PVN)
      of the hypothalamus, the lateral hypothalamus (LH), amygdaloid complex (AD) and
      thalamus (TH), and to a lesser extent, in the hippocampus (HP), caudate putamen
      (CP) and frontal cortex (FC). However, shocks did not alter the number of nNOS
      positive cells nor increased citrulline signals in these brain regions. LPS
      significantly upregulated the number of cells with fos-like ir in the PVN, LH,
      AD, TH, HP, CP and FC, but only increased the number of cells positive for
      citrulline in the PVN, 87% of which co-expressed Fos. Thus, while shocks did not
      alter nNOS gene expression or citrulline levels in the brain regions studied, LPS
      significantly increased the number of PVN cells expressing citrulline without
      concomitant changes in other brain areas. Endotoxemia also upregulated
      significantly more PVN cells that co-expressed Fos and nNOS, compared to shocks.
      As NO stimulates the PVN circuitries that participate in shocks- and LPS-induced
      ACTH release, the lack of changes in nNOS or citrulline levels due to shocks
      suggests that, in this model, constitutively formed NO may modulate HPA axis
      activity in the absence of changes in its synthesis.

PMID- 14725963
TI  - Electro-acupuncture preconditioning abrogates the elevation of c-Fos and c-Jun
      expression in neonatal hypoxic-ischemic rat brains induced by glibenclamide, an
      ATP-sensitive potassium channel blocker.
AB  - This study aimed to clarify the neuroprotective mechanism of electro-acupuncture
      (EA) preconditioning on hypoxic-ischemic brain injury (HIBI). Using Western blot,
      the expression of c-fos protein (c-Fos) and c-jun protein (c-Jun) induced by
      glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker was examined
      from cerebral cortical and hippocampal samples in neonatal hypoxic-ischemic rats,
      with or without EA preconditioning. EA was performed on Hegu (LI4), a well-known
      acupoint commonly used in Oriental medicine for the treatment of neuronal injury
      resulting from hypoxia-ischemia (HI). Preconditioned rats were treated with
      either diazoxide, a K(ATP) channel opener, glibenclamide, or sterile saline
      injected into the left lateral ventricle (i.c.v.), with or without EA
      administration before HI insult. Interestingly, low c-Fos and c-Jun expressions
      were found both in diazoxide and EA groups, 24 h after HI. Furthermore,
      significant differences in relative optical density (ROD) were found between
      glibenclamide and HI control groups (P< or =0.05), as well as between the group
      administered glibenclamide after EA and the HI control group (P< or =0.05).
      However, the level of c-Fos and c-Jun expression in the group administered
      glibenclamide after EA was significantly lower than in the glibenclamide group
      (P< or =0.05). The present findings indicate that the effectiveness of EA
      preconditioning against HIBI may be mediated via the opening of K(ATP) channels.

PMID- 14725964
TI  - Morphine- and cocaine-induced c-Fos levels in Lewis and Fischer rat strains.
AB  - Lewis (LEW) and Fischer 344 (F344) rat strains have been reported to differ in
      their sensitivity to the rewarding and aversive effects of both cocaine and
      morphine. Specifically, LEW rats self-administer morphine and cocaine to a
      greater extent than F344 rats, while LEW (compared to F344) rats are more
      sensitive to the aversive effects of cocaine but less sensitive to the aversive
      effects of morphine. Consistent with assessments of the rewarding effects of
      morphine and cocaine in these two strains, LEW rats have lower basal, and
      generally higher drug-induced, activity in brain regions associated with reward.
      Although the brain areas that mediate the aversive effects of drugs are becoming
      better defined, no studies have compared the activation of these areas by
      aversion-inducing drugs in the LEW and F344 strains. As such, the relationship
      between the ability of drugs to activate these aversion-associated brain areas
      and to induce a conditioned taste aversion (CTA) in these strains is unknown. To
      explore this relationship, LEW and F344 rats were injected with saline or doses
      of morphine or cocaine (32 mg/kg for both drugs) that have been shown to generate
      differential taste aversion learning in these strains. All animals were
      subsequently tested for c-Fos expression in areas of the brain associated with
      aversion learning (the lateral and medial parabrachial nucleus, intermediate and
      caudal nucleus tractus solitarius and area postrema), reward (the shell of the
      nucleus accumbens) and locomotion (the core of the nucleus accumbens and the
      caudate putamen). The present results indicated that patterns of morphine- and
      cocaine-induced c-Fos within CTA-associated, but not reward- or locomotor
      associated, brain regions paralleled the differential behavioral sensitivities of
      LEW and F344 rats to these drugs within CTA learning. Analyses with other drugs
      that do and do not induce aversions differentially would further assess the role
      of these brain areas in aversion learning, in general, and in strain-dependent
      differences, in particular.

PMID- 14725965
TI  - Association between inflammation and nigral neuronal damage following striatal
      excitotoxic lesion.
AB  - We examined the expression of TNF-alpha within the substantia nigra pars
      reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and
      studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal
      damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum
      of male Wistar rats. After survival of 1, 3 or 10 days, the animals were
      sacrificed and immunohistochemical staining with an antibody against TNF-alpha
      was performed. From day 1 to day 10 after striatal QA injection TNF-alpha
      positive cells were observed within ipsilateral substantia nigra which were
      neither present on the contralateral side nor in sham-operated controls. Double
      labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan
      or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that
      TNF-alpha positive cells are neurons. For the pharmacological approach, three
      groups of QA rats were treated intraperitoneally with either solvent (n=5), the
      NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor
      rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and
      continued with daily applications for 14 days. The amount of striatal damage did
      not differ between the three groups. The number of intact neurons within the
      ipsilateral substantia nigra of the solvent treated group was reduced by
      approximately 30% compared to the contralateral side. Both MK 801 and rolipram
      ameliorated this secondary damage and reduced the number of TNF-alpha positive
      cells. The observed association between expression of TNF-alpha and secondary
      neuronal damage within the substantia nigra induced by intrastriatal QA
      application might hint towards an involvement of this cytokine in transneuronal
      degeneration.

PMID- 14725966
TI  - Different types of barosensory synaptic inputs to rostral ventrolateral medulla
      neurons of the rat.
AB  - Neurons situated in the rostral ventrolateral medulla (RVLM) with descending
      axons to the spinal cord and that are modulated by different baroreceptor inputs
      are considered the main central generators of vasomotor activity. In the urethane
      anesthetized, curarized rat, we recorded intracellular potentials from 14 neurons
      located in the RVLM and investigated their barosensory properties by analysis of
      the relation between neuronal membrane potential (MP), including spike
      potentials, and high-pressure barosensory activity, which was indicated by
      arterial blood pressure (BLPR). Time-domain (cross-correlations or triggered
      averaging) and frequency-domain (autospectra and coherences) analysis showed that
      7 of 14 neurons had cardiac-cycle-correlated rhythms. EXCITATORY CARDIAC-CYCLE
      RELATED MODULATION: One type of barosensitive neuron, with strong cardiac-related
      activity, was antidromically activated from the spinal cord and received
      inhibitory inputs from aortic nerve stimulation. These neurons had strong pulse
      modulated activity consisting of EPSPs and spike potentials locked to the cardiac
      cycle and occurring at the end of diastole. INHIBITORY CARDIAC-CYCLE-RELATED
      MODULATION: Another type of barosensitive neuron showed hyperpolarizations locked
      to the cardiac cycle that started during late diastole and ended during the
      systolic period, but which had little relation to spike firing. The
      hyperpolarizations might be due to either IPSPs or disfacilitation. RESPIRATORY
      AND CARDIAC MODULATION: Some neurons also showed modulation of synaptic
      potentials and/or spike firing locked to the oscillation produced by ventilator
      pressure. It is suggested that the different types of cardiac- and respiratory
      related rhythm reflect different functional roles of neurons in baroreceptor
      regulation of vasomotor activity.

PMID- 14725967
TI  - Neural plasticity is impaired in cold-exposed hippocampal slices from senescent
      but not from age-matched presenescent F344 rats.
AB  - Near the end of their natural life, many mammals enter a terminal state
      identifiable by a rapid loss of body weight resulting from hypophagia. This study
      extends characterization of this senescent state by comparing viability of
      metabolic mechanisms supporting neural plasticity in hippocampal slices from 24
      to 30 month old senescent and age-matched presenescent (body-weight stable) F344
      male rats. Half of the slices from each rat were incubated at 22-23 degrees C,
      and half were immersed in cool incubation medium (12-15 degrees C) immediately
      after slicing and allowed to passively warm to room temperature over
      approximately 50 min to impose a cold stressor on recovery mechanisms. Following
      incubation, CA1 pyramidal cell population spike (PS) amplitudes were measured
      before and after tetanus. In slices incubated at 22-23 degrees C, the 221.0+/
      24.2 % increase in PS amplitude following tetanus in seven slices from five
      senescent rats was not significantly different from the 202.5+/-23.8% increase in
      six slices from five age-matched presenescent rats. In contrast, in cold-exposed
      slices, the 133.8+/-13.1% increase in PS amplitude following tetanus in 14 slices
      from 10 senescent rats was significantly smaller (p<0.05) than the 184.7+/-10.2%
      increase in 13 slices from seven age-matched presenescent rats. This smaller PS
      enhancement in senescent rats cannot be attributed to weight loss because robust
      potentiation was induced in cold-exposed slices from five food-restricted
      presenescent rats having a weight loss comparable to their senescent
      counterparts. Thus, the blunted enhancement observed in cold-exposed slices
      appears to be a characteristic of senescence.

PMID- 14725968
TI  - Activation of long-term synaptic plasticity causes suppression of epileptiform
      activity in rat hippocampal slices.
AB  - Electrical stimulation of cerebral targets for the treatment of epilepsy is an
      area under active investigation. Recent studies have shown that chronic
      stimulation of the subthalamic nucleus, fornix, or hippocampus may be effective
      in attenuating seizure frequency in animal models and in patients with
      intractable epilepsy. However, many questions exist, such as what are the
      specific electrical parameters, target sites, and mechanisms, etc., which should
      be investigated in animal studies before considering the routine use of chronic
      stimulation in epileptic patients. It is also important to understand what
      happens to neural activity during repetitive pulse stimulation as well as after
      stimulation. To this end, we hypothesized: (1) activation of synaptic plasticity
      suppresses epileptiform activity and (2) low frequency stimulation is an
      effective stimulation protocol for reducing seizure intensity and frequency. We
      used rat hippocampal brain slices to study how electrical stimulation affects
      spontaneous and evoked epileptiform activity. Further, we compared low (1 Hz)
      versus high (100 Hz) frequency stimulation in the same preparation. We found that
      orthodromic stimulation of the Schaffer collaterals for 10 min reduces the
      amplitude of normal responses and diminishes epileptiform activity. The onset of
      suppression by 1 Hz stimulation was gradual, but persistent, whereas the onset of
      suppression by 100 Hz was rapid; however, the effects of 100 Hz stimulation were
      transient. Finally, the NMDA antagonist, AP5 reversed the antiepileptic effects
      achieved by 1 Hz stimulation. Collectively, these data suggest that using
      different stimulation parameters prolonged electrical stimulation in the
      hippocampus may be effective in reducing seizure frequency in patients with
      epilepsy and that suppression by low frequency stimulation may be mediated by
      long-term depression (LTD).

PMID- 14725969
TI  - Lead stimulates ERK1/2 and p38MAPK phosphorylation in the hippocampus of immature
      rats.
AB  - Lead (Pb(2+)) is widely recognized as a neurotoxicant whose mechanisms of action
      are not completely established. We have previously demonstrated that Pb(2+) can
      activate the p38(MAPK) pathway and increase the phosphorylation of Hsp27 in
      bovine adrenal chromaffin cells and human SH SY5Y cells over a short incubation
      period (1 h). In the present work we analyzed the effects of Pb(2+) administered
      in vivo on the level and the phosphorylation state of ERK1/2 and p38(MAPK) in the
      hippocampus of immature rats. Rats were treated with lead acetate (2, 8 or 12
      mg/kg, i.p.) or saline (control) over the 8th to 12th postnatal days, and
      hippocampal slices were prepared on the 14th day. The Pb(2+) level in the lead
      treated animals increased 2.5-6-fold in the blood (3.0-6.0 microg/dl) and 2.0-3.0
      fold in the forebrain (78-103 ng/g wet weight), compared to control (saline). The
      phosphorylation of both ERK1/2 and p38(MAPK) was significantly increased by prior
      exposure to Pb(2+) in vivo. In in vitro experiments, hippocampal slices from 14
      day-old rats were exposed to Pb(2+) (1-10 microM) for 1 and 3 h. There were no
      changes in the phosphorylation state of ERK and p38(MAPK) for 1-h incubation,
      whereas a significant increase of ERK1/2 and p38(MAPK) phosphorylation by Pb(2+)
      (5 microM) was observed for the 3-h incubation. Cell viability measured using MTT
      was not modified in any of the conditions tested. These results indicate that the
      phosphorylation of hippocampal ERK1/2 and p38(MAPK) is stimulated by lead in a
      period of rapid brain development, an effect that may underlie, at least in part,
      the neurotoxicty elicited by this metal.

PMID- 14725970
TI  - Effects of amyloid-beta on cholinergic and acetylcholinesterase-positive cells in
      cultured basal forebrain neurons of embryonic rat brain.
AB  - The neurotoxic effects of amyloid-beta(1-42) and amyloid-beta(25-35) (A beta) on
      cholinergic and acetylcholinesterase-positive neurons were investigated in
      primary cultures derived from embryonic 18-day-old rat basal forebrain. After
      various time intervals, the cultures were treated with 1, 5, 10 or 20 microM A
      beta for different time periods. The cholinergic neurons and their axon terminals
      were revealed by vesicular acetylcholine transporter immunohistochemistry and the
      cholinoceptive cells by acetylcholinesterase histochemical staining. To assess
      the toxic effects of these A beta peptides on the cholinergic neurons, image
      analysis was applied for quantitative determination of the numbers of axon
      varicosities/terminals and cells. The results demonstrate that, following
      treatment with 1 or 5 microM A beta for 5, 10, 30, 60 or 120 min, no changes in
      vesicular acetylcholine transporter immunohistochemical staining were observed.
      However, after treatment for 30 min with 10 or 20 microM A beta, the number of
      stained axon varicosities was reduced, and treatment for 2 h they had
      disappeared. In contrast, vesicular acetylcholine transporter-positivity could be
      seen in some of the neuronal perikarya even after 3 days after treatment. The
      acetylcholinesterase staining was homogeneously distributed in the control
      neurons. After A beta treatment, the histochemical reaction end-product was
      detected in some of the neuronal perikarya or in the dendritic processes near to
      the soma. It is concluded that the neurotoxic effects of A beta appear more
      rapidly in the cholinergic axon terminals than in the cholinergic and
      acetylcholinesterase-positive neuronal perikarya.

PMID- 14725971
TI  - 5-Aza-2'-deoxycytidine stimulates inducible nitric oxide synthase induction in C6
      astrocytoma cells.
AB  - The influence of a nucleoside analog 5-aza-2'-deoxycytidine (5-AzadC) on
      inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) production in
      various rat cell types was investigated. In C6 astrocytoma cell line and primary
      astrocytes, 5-AzadC enhanced proinflammatory cytokine (IFN-gamma, TNF-alpha, IL
      1)-triggered NO synthesis in a time- and dose-dependent manner. In contrast, 5
      AzadC did not potentiate NO production in IFN-gamma-stimulated macrophages,
      fibroblasts, or endothelial cells. Blockade of transcription or translation in C6
      cells abolished the observed effect, suggesting the iNOS gene expression, rather
      than its catalytic activity, as a target for the drug action. Accordingly, 5
      AzadC upregulated IFN-gamma-induced expression of iNOS mRNA in C6 astrocytes. The
      effect of 5-AzadC on astrocyte NO release was blocked by the inhibitor of p44/42
      mitogen activated protein kinase-dependent signaling. Finally, the observed
      stimulatory effect of 5-AzadC on iNOS expression was apparently independent of
      DNA demethylation, as DNA digestion with methylation-sensitive restriction enzyme
      HpaII showed that 5-AzadC failed to demethylate cellular DNA in conditions used
      for iNOS induction.

PMID- 14725972
TI  - The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan
      inhibit trigeminovascular input to the nucleus tractus solitarius in the cat.
AB  - Migraine pain arises in the trigeminovascular system and is often associated with
      nausea and sometimes with vomiting. In this study, an in vivo cat model of
      trigeminovascular stimulation was used to determine first whether there is a
      functional connection between the trigeminovascular system and the nucleus
      tractus solitarius (NTS), which is involved in regulating vomiting, and second
      whether anti-migraine drugs have any effect on such a connection. Chloralose
      anaesthetised cats (n=16) were prepared for single neuron recording. The superior
      sagittal sinus (SSS) was isolated and stimulated electrically. The brainstem near
      the obex was exposed and a metal microelectrode equipped with six glass barrels
      for microiontophoresis was placed in the NTS. Recordings were made from 44 NTS
      neurons which responded to SSS stimulation with A-delta latencies. Iontophoretic
      ejection (50 nA) of eletriptan or naratriptan suppressed the response in 75%
      (15/20) and 78% (11/14) of cells and caused an average suppression of cell firing
      of 42+/-5% (n=20) and 54+/-8% (n=14), respectively. This suppression could be
      antagonized by the concurrent ejection (20-50 nA) of the 5-HT(1B/1D) receptor
      antagonist GR127935. We conclude that activation of the trigeminovascular system
      excites cells in the NTS that can be inhibited by eletriptan and naratriptan
      through activation of 5-HT(1B/1D) receptors. It is possible that in patients
      having a migraine attack trigeminovascular activation triggers nausea and
      vomiting, and that the alleviation of these symptoms by anti-migraine compounds
      may be via an action at 5-HT(1B/1D) receptors in the NTS.

PMID- 14725973
TI  - The blood supply of the cat's visual cortex and its postnatal development.
AB  - We examined the blood supply of the cat's visual cortex using alkaline
      phosphatase histochemistry to demonstrate the capillary endothelial cells. In the
      adult, layer 4 is marked by a band that is of obviously greater density, extends
      throughout areas 17 and 18, and ends abruptly at the 18/19 border. We quantified
      blood vessel density in area 17, observing a 23% greater density in layer 4 than
      in supragranular and infragranular layers. This difference reflects a laminar
      difference in metabolic rate. In three animals studied using the metabolic marker
      2-deoxyglucose, layer 4 was 25% denser than the other layers. The band of greater
      density in layer 4 is not present in newborn kittens, but becomes apparent at
      about 5 weeks of age. Early in development, the endothelial cells form filopodia
      as the capillaries grow and branch. The density of blood vessels decreases
      slightly during the first week of postnatal life, but increases between 1 and 6
      weeks of age, so that by 6 weeks, the blood supply of the visual cortex resembles
      that seen in the adult. This pattern resembles that of cortical metabolism seen
      with 2-deoxyglucose [J. Cereb. Blood Flow Metab. 11 (1991) 35], but the increase
      in vascular density precedes that in glucose metabolism.

PMID- 14725974
TI  - Evaluation of estrous cycle stage and gender on behavioral outcome after
      experimental traumatic brain injury.
AB  - Female sex hormones are acutely neuroprotective in experimental models of
      traumatic brain injury (TBI). Because hormonal profiles are known to vary with
      estrous cycle stage, the purpose of this study was to evaluate how pre-injury
      estrous stage affects motor and cognitive performance after experimental TBI. We
      also sought to compare post-injury behavioral performance in males vs. females.
      Under anesthesia, male (n=18) and female (n=35) Sprague-Dawley rats underwent
      either controlled cortical impact (CCI) injury (2.7 mm; 4 m/s) or sham
      operations. Females were grouped according to estrous stage (proestrous or non
      proestrous) at the time of surgery. Motor function was assessed pre-injury and
      for the first 5 days after surgery using beam balance and walking tasks. Spatial
      memory was assessed beginning 14 days post-injury utilizing the Morris water maze
      (MWM) task. No significant differences were found on any task between injured
      females regardless of estrous cycle stage. Females performed significantly better
      than males on both motor tasks, but gender did not influence MWM performance.
      Mixed effects multivariate analysis corroborated these results by showing that
      pre-injury serum hormone levels had little affect on behavioral performance. The
      results suggest that the presence of endogenous circulating hormones, rather than
      hormonal status at time of injury, may confer early neuroprotection in females
      after TBI. The impact of early neuroprotection on later behavioral outcome and
      the anatomic structural specificity of hormonal neuroprotection require further
      study.

PMID- 14725976
TI  - The co-expression of P2X3 receptor with VR1 and VRL-1 in the rat trigeminal
      ganglion.
AB  - The co-expression of P2X3 receptor with the vanilloid receptor subtype I (VR1)
      and vanilloid receptor 1-like receptor (VRL-1) was examined in the rat trigeminal
      ganglion (TG) by a double immunofluorescence method. P2X3 receptor-immunoreactive
      (ir) neurons were predominantly small to medium-sized (range=93.8-1844.4
      microm(2), mean+/-S.D.=503.8+/-286.5 microm(2)); 35% and 9% of P2X3 receptor-ir
      TG neurons were immunoreactive for VR1 and VRL-1, respectively. Small and medium
      sized P2X3 receptor-ir neurons contained VR1-immunoreactivity (ir), whereas
      medium-sized and large P2X3 receptor-ir neurons showed VRL-1-ir. The retrograde
      tracing and immunohistochemical methods revealed that 30% of the TG neurons
      retrogradely labeled from the facial skin and tooth pulp exhibited P2X3 receptor
      ir. The co-expression of P2X3 receptor and VR1 was detected in 16% of cutaneous
      TG neurons and 6% of tooth pulp neurons. On the other hand, the co-expression of
      P2X3 receptor and VRL-1 was common in tooth pulp neurons (23%) and rare in
      cutaneous TG neurons (8%). In the tooth pulp, 95% of P2X3 receptor-ir TG neurons
      contained VRL-1-ir. The present study indicates that P2X3 receptor-ir TG neurons,
      which co-express VR-ir, are abundant in the facial skin. The tooth pulp is
      probably innervated by TG neurons, which contain both P2X3-and VRL-1-ir.

PMID- 14725975
TI  - Comparison of mice deficient in the high- or low-affinity neurotensin receptors,
      Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception.
AB  - Neurotensin (NT) is a neuropeptide that induces a wide range of biological
      activities including hypothermia and analgesia. Such effects are mediated by the
      NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in
      specific NT functions remains unknown. To address nociceptive function in vivo,
      we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition,
      histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse
      brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA
      was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral
      ventral medulla (RVM). The mutant and control mice were subjected to the
      examination of thermal nociception, and in the hot plate test, a significant
      alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1
      deficient or wild-type control mice. Latencies of tail flick and hind paw licking
      of the mutant mice were not affected compared to control mice. These results
      suggest that Ntsr2 has an important role in thermal nociception compared to
      Ntsr1, and that these mutant mice may represent a useful tool for the development
      of analgesic drugs.

PMID- 14725977
TI  - Alleviation of ischemic neuronal damage by postischemic loading with histidine in
      the rat striatum.
AB  - Inflammatory reactions play an important role in ischemia-reperfusion injury in
      the brain. Since histamine H(2) action suppresses inflammatory reactions, effects
      of postischemic loading with histidine, a precursor of histamine, were examined.
      Focal cerebral ischemia for 15 min was provoked by transient occlusion of the
      right middle cerebral artery in rats, and delayed neuronal death were evaluated
      in striatal neurons after 7 days. Histidine was administered four times,
      immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p.,
      each time). To examine the role of histaminergic action on changes in histologic
      outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and
      ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine
      treated rats. Transient ischemia for 15 min provoked severe neuronal damage in
      the saline-injected control group, and the number of striatal neurons decreased
      to 21% of that on the contralateral side. Administration of histidine alleviated
      ischemic neuronal damage, and the number of preserved neurons was 76% of that on
      the contralateral side. Simultaneous administration of mepyramine with histidine
      did not affect the histologic outcome. However, administration of ranitidine
      abolished the alleviation by histidine. These findings indicate that the
      elevation of histamine H(2) receptor stimulation by massive administration of
      histidine suppresses reperfusion injury in the brain.

PMID- 14725978
TI  - Assessing candidate children for cochlear implantation with the Nottingham
      Children's Implant Profile (NChIP): the first 200 children.
AB  - BACKGROUND/OBJECTIVE: Nottingham Children's Implant Profile (NChIP) is a profile
      designed to assess candidate children for cochlear implantation. It includes the
      demographic details of the children (chronological age and duration of deafness),
      medical and radiological conditions, the outcomes of audiological assessments,
      language and speech abilities, multiple handicaps or disabilities, family
      structure and support, educational environment, the availability of support
      services, expectations of the family and deaf child, cognitive abilities, and
      learning style. The aim of the present study is to present the NChIP data
      obtained on the first 200 children implanted in the same cochlear implant
      programme and evaluate NChIP's use in the selection phase of cochlear
      implantation. PATIENTS: The study assessed 200 profoundly deaf children. Fifty
      six children (28%) were deafened by meningitis, 132 (66%) were born deaf, and 12
      (6%) were deafened from other causes (head injury, viral infection, progressive
      deafness). RESULTS: Chronological age at the time of assessment (before
      implantation) was the most common factor of major concern (9% of the children
      studied) and the pre-implant language and speech abilities of the children was
      the most common factor of mild to moderate concern, affecting 63% of the
      children. The second most common factor of mild to moderate concern was duration
      of deafness (37%) and the third was the learning style of the children (33%).
      Availability of support services was the least factor of concern as 179 children
      (90%) did not have any problems in this area. CONCLUSIONS: Earlier identification
      of deafness (by universal neonatal hearing screening programs) may reduce age at
      implantation and duration of deafness as areas of concern in the future. However,
      the pre-implant language and speech abilities of the candidate children, the gap
      between chronological and language age, and the learning style of children are
      now emerging as key areas of research in the field. NChIP was found to be a very
      useful casework tool in the initial evaluation of the deaf children promoting and
      enhancing interdisciplinary teamwork across the different professionals. NChIP
      was also used as part of the decision-making process by the cochlear implant
      programme professionals and as a counselling tool for the parents. Finally, NChIP
      has helped to identify those children and families who need additional support.
      In the case of recently established paediatric cochlear implant programmes it
      would be a 'neutral' yet sensitive way of promoting good interdisciplinary
      collaboration and also peer support within team discussions when selecting
      children for cochlear implantation.

PMID- 14725979
TI  - Predicting speech perception outcomes following cochlear implantation using
      Nottingham children's implant profile (NChIP).
AB  - BACKGROUND/OBJECTIVE: Nottingham children's implant profile (NChIP) is a
      systematic framework to assess deaf children before implantation taking into
      account not only the well-known factors (age, duration of deafness) but also
      family and support services, expectations, children's cognitive abilities and
      learning style. The aim of the present paper is to assess the predictive value of
      the NChIP in the long-term outcomes of implanted children. PATIENTS: This
      prospective and longitudinal study involved 51 profoundly deaf children,
      implanted within the same paediatric cochlear implant programme. All children
      were pre-lingually deaf with age at onset of deafness <2 years and age at
      implantation <6 years. Three and 4 years following implantation all children were
      assessed using two measures of speech perception. No child was lost to follow-up
      and no child was excluded from the study for any reason. RESULTS: The most
      constant predictor of the outcomes was children's learning style explaining upto
      29% of the variance. Other significant predictors of the outcome were shorter
      duration of deafness, young age at implantation and family structure/support.
      CONCLUSIONS: Intrinsic factors in children and how well they communicate with
      their environment are of paramount importance to the outcome following
      implantation. The predictive value of NChIP has been demonstrated and the most
      important predictors of the outcome were children's learning style, short
      duration of deafness, young age at implantation, and family structure/support.

PMID- 14725980
TI  - Paediatric small cavity mastoid surgery: second look tympanotomy.
AB  - OBJECTIVE: Following surgery for retraction pocket/cholesteatoma there is risk of
      residual disease, after canal wall up surgery a second look tympanotomy is
      routinely recommended. After canal wall down (CWDM) surgery this is not routine.
      In certain situations the senior author recommends second look tympanotomy. This
      report examines the outcome of this management paradigm applied to small cavity
      mastoid surgery for children. METHOD: A retrospective review of small cavity
      mastoid surgery for children with cholesteatoma or discharging retraction pocket
      disease. The primary procedure and surgical findings at second look tympanotomy
      are reported as well as the pre- and 1 year post-operative air and bone
      conduction thresholds and air-bone gap averaged across frequencies 0.5, 1, 2 and
      4kHz and the mean pre- and post-operative bone conduction threshold at 4kHz. A
      Student t-test was used to compare hearing results. RESULTS: Forty five were
      children reviewed at 1 year. Twelve (27%) were recommended second look
      tympanotomy, of which 10 had surgery; all were free of residual disease. At
      second look two children had ossiculoplasty performed, four had adhesions
      divided. Six children had formed a myringostapediopexy after their first surgery.
      The mean pre-op bone conduction threshold was 6.3dB for those having single stage
      surgery and 5.6dB for those having a second look and the post-operative
      thresholds were 7.8 and 10.2dB, respectively. The mean preoperative air
      conduction threshold was 32.6dB for single stage surgery and 31.1dB for staged
      surgery and at 1 year 29.2 and 40.8dB. This was a significant difference. After
      second look, the air conduction threshold was 34.5dB, and not significantly
      different from those who had single stage surgery. The mean pre-treatment 4kHz
      bone conduction threshold was 6.3 and 5.6dB for single stage surgery and second
      look tympanotomy and after surgery, respectively, 9.8 and 14.5dB. These changes
      are not statistically significant. CONCLUSION: The small cavity mastoidectomy
      approach allows meticulous removal of disease from the middle ear and for certain
      indications second look tympanotomy is recommended. Planned second look
      tympanotomy has demonstrated excellent early disease control as well as allowing
      timely management of any pathology affecting the middle ear sound transformation
      mechanism.

PMID- 14725981
TI  - Parents and their cochlear implanted child: questionnaire development to assess
      parental views and experiences.
AB  - OBJECTIVES: To test the reliability of a validated closed-format questionnaire
      assessing parental views following cochlear implantation of their child. DESIGN:
      Parents were surveyed using a closed-format questionnaire developed in earlier
      work. The same parents were surveyed 1 month later and responses compared. Test
      retest reliability was thereby assessed. SETTING: Tertiary referral Pediatric
      Cochlear Implant Centre in the UK. SUBJECTS AND METHODS: The parents of 20
      children who had been born deaf or were deafened by age 3 years and who had been
      implanted for at least 2 years were drawn at random from patient lists. Parents
      were surveyed using a closed-format questionnaire whose validity had been
      previously assessed and re-surveyed 1 month later. Responses over time were
      compared. RESULTS: For the majority of items in the questionnaire, the
      replication of the item would lead to the same response on at least 95% of
      occasions. The text of the closed-format questionnaire is reproduced in full.
      CONCLUSION: This validated closed-format questionnaire appears to be unique in
      respect of cochlear implantation, being based explicitly on issues thought
      important by the parents. The high test-retest reliability indicates that it is
      capable of eliciting parental views in a meaningful manner. This information that
      is not currently available by other means can then be used as part of an overall
      assessment of outcomes, to inform efforts aimed at quality improvement as well as
      demonstrating accountability to purchasers and policymakers. Moreover, a wider
      use of this instrument can result in valid comparisons of outcomes among
      different cochlear implant centres.

PMID- 14725982
TI  - Surgical management of pediatric ranula.
AB  - OBJECTIVE: Many surgical techniques have been described in the literature and
      their recurrence rates have been compared. Few studies have compared the results
      of the most popular techniques such as excision and marsupialization in pediatric
      population. METHODS: Sixteen children were operated for ranula. Total excision
      with sublingual gland was performed on 10 patients while marsupialization was
      performed on 6 patients. These patients were followed up at least 3 years. Their
      charts were investigated retrospectively. RESULTS: The age range was between 17
      days and 16 years old. The mean age was 9 years. There were 12 females and 4
      males. One patient (6.25%) had recurrence after excision and marsupialization was
      performed on this patient. The recurrence rates for marsupialization and excision
      were 0 and 10%, respectively. Ranulas were ruptured during surgery in 11 cases
      (68.75%) while a defect on the floor of the mouth had occurred in 1 patient. Only
      one of the cases among ruptured cases (9%) had reoccurred. The most common
      complication was rupture of the ranula in 11 patients (68.75%) followed by a
      defect on the floor of the mouth in one case. CONCLUSION: Rupture of the cyst
      during surgery does not increase the risk of recurrence. Besides marsupialization
      or excision do not make any difference in terms of success of surgery.

PMID- 14725983
TI  - Voluntary progress toward universal newborn hearing screening.
AB  - OBJECTIVES: This study assessed the prevalence of newborn hearing screening in
      Wisconsin between 1997 and 2001, and examined factors leading to establishment of
      programs and influencing the outcomes of universal newborn hearing screening
      (UNHS). The primary goal was to identify characteristics that might be important
      for states, provinces or countries that have not yet implemented UNHS programs
      and to examine some unique components of the Wisconsin UNHS program, that may
      provide direction to areas both with and without programs. METHODS: The study
      consisted of two cross-sectional surveys administered at two separate time points
      (2000 and 2001). Additional data was provided by the Wisconsin Sound Beginnings
      Early Detection and Hearing Intervention database. RESULTS: Between 1997 and
      2001, the number of Wisconsin birthing hospitals with UNHS programs increased
      from two to 92 of a total of 103 and the percent of all Wisconsin newborns
      screened for hearing loss before 1-month of age increased from 10 to 90%. In
      2001, 2.6% of screened newborns had an abnormal test requiring further audiologic
      evaluation, with a higher rate of referral in programs relying only on
      otoacoustic emission testing versus automatic auditory brainstem testing. As
      programs were being established, hospitals with greater number of deliveries more
      readily developed UNHS programs and hospitals with more deliveries were also
      significantly more likely to screen a greater percentage of delivered children
      once their programs were established. The Wisconsin Sound Beginnings program
      established a screening program for home birth infants in 2002 with a current
      screen rate of 79% for those midwives participating in this program. CONCLUSIONS:
      A vast majority of Wisconsin hospitals have voluntarily implemented UNHS
      programs. By 2001, greater than 90% of all Wisconsin newborns were screened
      through a UNHS program. With education, financial support and a statewide network
      dedicated to UNHS it is possible to establish programs even for infants born in a
      setting that should be considered high-risk to miss hearing screening, such as
      home births and hospitals that perform relatively few numbers of deliveries per
      year. UNHS programs need to develop coordinated systems for linking these
      programs to audiologic diagnostic services and early intervention programs.

PMID- 14725984
TI  - Auditory neuropathy/auditory dys-synchrony in school children with hearing loss:
      frequency of occurrence.
AB  - OBJECTIVE: The frequency of occurrence of a recently identified hearing disorder,
      auditory neuropathy/auditory dys-synchrony (AN/AD), was investigated in children
      with hearing impairment in Hong Kong. METHODS: In this study, 56 students, aged 7
      18 years, attending primary divisions in schools for the hearing impaired were
      screened using otoacoustic emission procedures. RESULTS: One student in the study
      group was found to have intact outer hair cell function. A detailed diagnostic
      assessment of this case strongly suggested AN/AD was involved. Combining the
      study results with those of a previously conducted survey in Hong Kong, the
      frequency of occurrence of AN/AD in children attending schools for the hearing
      impaired was estimated to be 2.44% (3 out of 123 children screened). Estimates of
      the frequency of occurrence of AN/AD in various other educational settings in
      Hong Kong were also derived. CONCLUSIONS: The study indicates that AN/AD is not
      an extremely rare disorder. Educational audiologists and other health care
      professionals need to be actively involved in the identification and management
      of AN/AD. Research should be directed at technological innovations that may help
      to overcome the limitations of present screening procedures, in order to more
      accurately identify the disorder.

PMID- 14725985
TI  - Community-based newborn hearing screening program in Taiwan.
AB  - OBJECTIVE: Congenital bilateral hearing impairment occurs in approximately 1 in
      every 1000 live births. Universal newborn hearing screening (UNHS) programs are
      the most effective method for early diagnosis. Previously, newborn hearing
      screenings in Taiwan were often hospital-based. Our study is a community-based
      program designed to test the feasibility of performing neonatal hearing screening
      with a pay-for-test model, and to evaluate its acceptability to parents. METHODS:
      From March 2000 to December 2002, two hospitals and four obstetric clinics in
      Tainan city participated in this study. The subjects were healthy newborns whose
      parents agreed to pay for otoacoustic emissions (OAE) hearing screening. They
      were tested in the newborn nursery before discharge. The protocol used an initial
      transient evoked otoacoustic emissions screening followed by a diagnostic
      auditory brainstem response (ABR) test. RESULTS: A total of 10,008 healthy
      neonates were recruited, and 5938 newborns (59.3%) were tested. Prior to hospital
      discharge, 5403 of the newborns (91.0%) had passed the transient evoked
      otoacoustic emissions test. Referral for further testing was made in 9.0% of
      cases (535/5938). There were 140 babies lost to 1-month follow up. Only 395
      infants (73.8%) of the infants that failed their first otoacoustic emissions
      tests underwent a second session at the outpatient clinic, and 91 babies failed.
      They were referred for further auditory brainstem response testing. Ultimately,
      nine babies were diagnosed with sensorineural hearing loss (SNHL). CONCLUSIONS:
      There are difficulties in performing universal newborn hearing screening within
      Taiwan's health insurance system. This study was performed with the cooperation
      of hospitals and obstetric clinics, and was undertaken with a pay-for-screening
      model. Our program, with a pay-for-test model, of newborn hearing screening is
      feasible and was well regarded by parents in Tainan city. It could be run without
      the government's financial support.

PMID- 14725986
TI  - The effect of the season on otitis media with effusion resolution rates in the
      New York Metropolitan area.
AB  - OBJECTIVE: To study the relationship between season and resolution rates of
      otitis media with effusion (OME) in the New York Metropolitan area, in order to
      provide objective data useful to the practicing otolaryngologist in determining
      if seasonal factors should be considered in OME management decisions. METHODS:
      This was a prospective study of children referred to a tertiary medical center.
      Children with OME (confirmed by pneumatoscopy and tympanometry) were followed by
      an otologist at an academic medical center over a 3 years period. They returned
      approximately every 6 weeks until the end points of resolution of the effusions
      or ventilating tube placement. Each period between visits is termed an
      "interval." RESULTS: 127 patients with 231 effusions were followed for a total of
      354 intervals. Effusions at intervals beginning in autumn were least likely to
      resolve by the next visit (24.29%) while intervals ending in the summer had the
      greatest rate of resolution (44.32%). Analyzed by month, the lowest rates of
      resolution were seen in intervals beginning in September, November, February, and
      March (16.67, 21.05, 20.51, and 19.15%, respectively). Intervals beginning in May
      had the greatest chance of resolution (51.72%). There was a positive correlation
      between resolution rates and average daily temperatures as reported by month.
      CONCLUSIONS: The season and month of the year are relevant factors in the
      clinical course of OME in the New York Metropolitan area. Based on the observed
      rates of resolution, one could reasonably consider taking a more conservative
      approach to OME management in May through August, and a more aggressive approach
      in the fall and winter months.

PMID- 14725987
TI  - Eustachian tube function and tympanic membrane findings after chronic secretory
      otitis media.
AB  - OBJECTIVE: The etiology of secretory otitis media (SOM) is multifactorial. The
      main factors discussed are infection and tubal dysfunction. This study aimed to
      detect poor tubal function and tympanic membrane pathology in young adults after
      extremely long-standing SOM. METHODS: Thirty-four patients, 16-25 years old, with
      previous chronic SOM persisting at least 6 years (mean 11.2 years, range 6.2-18.6
      years), were retrospectively examined at a mean of 18 years after their first
      myringotomy or tube insertion and comparison was made with 15 controls. The
      medical records were scrutinized, otomicroscopic examination was performed and
      the Eustachian tube function was studied in a mini pressure chamber. RESULTS: The
      mean age at SOM onset was 2.4 years (range 0.5-8.4 years) and the mean period
      from the last myringotomy or when the last tube had disappeared to follow-up was
      6.7 years (range 1.3-12.8 years). Tympanic membrane pathology was found in 76% of
      the ears of SOM patients and in none (0%) of controls (P<0.001). The youngest
      patients had more atrophy than the older patients (P<0.05) and more
      myringosclerosis was observed in patients with shorter interval between SOM
      ending and examination. The patients were found to have significantly poorer
      active tubal function; i.e. higher inability to equilibrate negative or negative
      and positive middle ear pressure, compared with controls (P<0.001). The majority
      of the patients (74%) still experienced some kind of discomfort in their ears at
      the time of examination. CONCLUSIONS: Still in adulthood patients with chronic
      SOM during childhood exhibit dysfunction of the tube and tympanic membrane
      pathology to a high extent.

PMID- 14725988
TI  - Presence of human herpesviruses in young children with acute otitis media.
AB  - Some herpesviruses have been detected in middle ear fluid (MEF) of patients with
      acute otitis media (AOM), but their role in middle ear disease is unknown. We
      examined 73 middle ear fluid samples from 73 children with acute otitis media for
      the presence of four major herpesviral DNA, respiratory viral genomes, and
      bacterial DNA by multiplex polymerase chain reaction (PCR). Herpesviruses were
      detected in 16 specimens (22%), with 18 viral infections were identified overall.
      Respiratory viruses were detected in 35 specimens (48%), 39 viral infections
      overall. Bacterial DNA was detected in 51 specimens (70%), 60 bacterial
      infections overall. Clinical outcome was compared in patients with and without
      herpesvirus DNA, respiratory viral genomes, or bacterial DNA. Progression to
      otitis media with effusion (OME) was more common when herpesviral DNA was
      present. Presence of herpesvirus DNA may reflect an immunocompromised state that
      may make it difficult to eliminate bacteria from the middle ear after infection.

PMID- 14725989
TI  - Extensive tongue hemangiopericytoma in a child: modified combined modality of
      treatment to preserve well functioning tongue.
AB  - Hemangiopericytoma is a rare vascular tumor, usually occurring in adults. The
      tumor is believed to originate from pericytes, the contractile cells surrounding
      capillaries. It has predilection for the musculoskeletal system. Clinically, the
      tumor occurs at any age, with highest incidence between the third and sixth
      decades and without any sex predilection. Head and neck hemangiopericytoma
      incidence in all age groups ranges from 9.4 to 28%. In children, head and neck
      hemangiopericytoma is as frequent as 35%, with the highest frequency (46%) found
      in infants. We report a case of hemangiopericytoma of the tongue in a 6-year-old
      child resembling to the infantile/congenital type, which was treated by a
      combination of surgery, chemotherapy, and brachytherapy. This approach has
      resulted in a normal functioning tongue for the past 5 years.

PMID- 14725990
TI  - A sinonasal primary Ewing's sarcoma.
AB  - Nasal fractures are a common complaint familiar to all otolaryngologists.
      Sinonasal primary Ewing's sarcomas are extremely rare. The case of a 9-year-old
      boy is presented whose nasal fracture and subsequent lateral nasal wall hematoma
      revealed an underlying Ewing's sarcoma. There are several unusual features in the
      history and clinical course of this patient. Following biopsies,
      immunohistochemistry proved essential in distinguishing a Ewing's sarcoma from
      other small cell tumours. It is important that a seemingly common condition can
      be the first presentation of a less common, more sinister pathology.

PMID- 14725991
TI  - Ossifying fibromyxoid tumor of the ethmoid sinus in a newborn: report of a case
      and literature review.
AB  - Ossifying fibromyxoid tumor (OFT) of soft parts is a benign soft tissue tumor
      commonly located in the extremities. In this paper, a 3-week-old boy presented
      with left nasal mass at birth. He was found to have an OFT involving the ethmoid
      sinus. To the best of our knowledge, this is the first reported case of OFT in a
      newborn with involvement of the sinuses. This rare tumor should alert Pediatric
      Otolaryngologists to include it in the differential diagnosis of pediatric soft
      tissue tumors in sinuses.

PMID- 14725992
TI  - The successful management of congenital laryngeal web with endoscopic lysis and
      topical mitomycin-C.
AB  - Laryngeal web is a rare congenital anomaly. The primary goals of management for
      congenital laryngeal web are to provide a patent airway and to achieve a good
      voice quality. However, vocal cords have a tendency for fibrosis and granulation
      tissue formation after surgical interventions. Traditionally, the treatment of
      choice for laryngeal web is laryngofissure and placement of a stent or keel. This
      report presents the successful management of a congenital laryngeal web in a 10
      month-old boy with endoscopic lysis and topical mitomycin-C application.

PMID- 14725993
TI  - Hyperparathyroid crisis in a pediatric patient.
AB  - Primary hyperparathyroidism is rarely found in the pediatric population. Delays
      in diagnosis due to vague symptoms can lead to severe disease manifestations such
      as osteitis fibrosa cystica. We report a rare case of primary hyperparathyroidism
      in a 13-year-old girl who presented with a pathological femur fracture and
      numerous brown tumors.

PMID- 14725994
TI  - Wolfram syndrome.
AB  - The Wolfram syndrome is a rare dysmorphogenetic disease of autosomic recessive
      hereditary nature. The pathogenesis of the disease is still not well known. It is
      characterised by the presence of diabetes insipidus, diabetes mellitus, optic
      atrophy and deafness. Other anomalies, such as renal outflow tracts and multiple
      neurological disorders may develop later. In our case report the diabetes
      mellitus appeared at the age of 4; the hearing loss and renal disturbances at the
      age of 11; the optic atrophy at the age of 16. No signs of ataxia, diabetes
      insipidus and neurologic anomalies were found. The diagnosis of Wolfram syndrome
      is not always easy in the first stages of the disease. The suspect may come from
      the presence of a juvenile diabetes mellitus asssociated with optic atrophy. For
      the diagnosis a valid clue can be given from the results of some clinical tests
      such as the positivity of the visual evoked potentials and the retinogram reliefs
      and the exclusion of the autoimmune origin of the diabetes mellitus. Other signs
      such as the progressive sensorineural hearing loss, the presence of nystagmus and
      of urodynamic disturbances and renal complications makes the diagnosis of this
      syndrome easier.

PMID- 14725995
TI  - Feeding difficulties in a neonate with primary cricopharyngeal achalasia treated
      by cricopharyngeal myotomy.
AB  - Primary cricopharyngeal achalasia resulting from failure of relaxation of the
      cricopharyngeus muscle is a rare but significant cause of dysphagia in newborns.
      Symptoms may be nonspecific. Although surgical management with cricopharyngeal
      myotomy has been employed successfully for the treatment of this disorder,
      swallowing difficulties may persist postoperatively, probably due to association
      with other esophageal abnormalities. Alternative methods of feeding may be
      required to ensure adequate nutrient intake. We report the case of a full-term, 2
      day-old neonate with this rare clinical condition, treated by myotomy, in whom
      swallowing difficulties persisted for several weeks after surgery. Satisfactory
      nutrition was maintained postoperatively with the support of a nasogastric
      feeding tube until improvement in feeding intolerance. Complete symptomatic
      relief was attained at the age of 5 months.

PMID- 14725997
TI  - Solid-liquid phase behavior of binary fatty acid mixtures. 1. Oleic acid/stearic
      acid and oleic acid/behenic acid mixtures.
AB  - Solid-liquid phase behavior of binary fatty acid mixtures was investigated by
      means of differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (FT-IR) for the mixture composed of oleic acid (OA) and stearic acid
      (SA) and that composed of OA and behenic acid (BA). The DSC results provided a
      monotectic type T-X phase diagram for these mixtures, from which it was suggested
      that the two fatty acid species are completely immiscible in a solid phase
      regardless of the two polymorphs of OA, i.e., alpha-form or gamma-form. The solid
      phase immiscibility was confirmed by the FT-IR observation that the spectra
      obtained for the mixtures correspond to the superposition of the two spectra for
      respective components. Thermodynamic analysis of liquidus line demonstrated that
      OA and SA form an ideal mixture in a liquid phase, whereas the mixing of OA and
      BA in a liquid phase is slightly non-ideal.

PMID- 14725996
TI  - Effect of phytosterols and phytostanols on the solubilization of cholesterol by
      dietary mixed micelles: an in vitro study.
AB  - The effect of a plant sterol, beta-sitosterol (SI), and a plant stanol,
      sitostanol (SS), on the solubilization of cholesterol (CH) by model dietary mixed
      micelles was examined under in vitro conditions with the use of gas
      chromatography, isothermal titration calorimetry, NMR spectroscopy and cryogenic
      transmission electron microscopy techniques. Free SI and SS were shown to reduce
      the concentration of CH in dietary mixed micelles via a dynamic competition
      mechanism. CH, SI and SS affect the microstructure of lipid vesicles and
      influence the process of amphiphilic self-assembly of nutrients in the gut with
      the formation of dietary mixed micelles in a similar manner. Therefore,
      substitution of CH by phytosterols and phytostanols in the diet does not lead to
      the notable changes in the mechanism of dietary mixed micelle formation and does
      not affect the process of the intestinal transport of nutrients and drugs via the
      micellar diffusion mechanism. Our experimental findings demonstrate that the
      introduction of plant sterols and plant stanols into the diet is clearly
      beneficial for the reduction of the intestinal uptake of cholesterol. Due to the
      limited capacity of dietary mixed micelles to embody hydrophobic sterol/stanol
      molecules, the micellar concentration of cholesterol is reduced and hence, its
      transport towards the intestinal brush border membrane decreases.

PMID- 14725998
TI  - The kinetics and mechanism of the formation of crystalline phase of
      dipalmitoylphosphatidylethanolamine dispersed in aqueous dimethyl sulfoxide
      solutions.
AB  - The phase transition kinetics and mechanism of formation of a lamellar
      crystalline phase of dipalmitoylphosphatidylethanolamine (DPPE) dispersed in
      different concentrations of aqueous dimethyl sulfoxide (DMSO) during cooling have
      been examined by differential scanning calorimetry and synchrotron X-ray
      diffraction techniques. In dispersions containing mole fractions of DMSO
      (x<0.22), the phase transition sequence of the phospholipid is from lamellar
      liquid-crystal phase to lamellar-gel phase. Increasing the mole fraction of DMSO
      to 0.22<x<0.50 induced the formation of a lamellar crystal phase from the gel
      phase. The proportion of gel phase converted to the lamellar crystal phase
      increased with DMSO concentration. Dispersion of phospholipid in aqueous DMSO
      solutions when x>0.5 resulted in a direct transition from liquid-crystal phase to
      lamellar crystal phase with no detectable intermediate gel phase. A temperature
      versus DMSO concentration phase diagram was constructed based on calorimetric
      data with phase assignments made using synchrotron X-ray diffraction
      measurements. The non-isothermal formation kinetics of the lamellar crystal
      phase, which is expressed as the half time of the transformation process, was
      found to depend on DMSO concentration. The inducement of lamellar crystal phase
      in DPPE by DMSO is discussed in terms of the dehydration effect of DMSO and
      competitive molecular interactions between DMSO, water, and the phospholipid.

PMID- 14725999
TI  - Solid-liquid phase behavior of binary fatty acid mixtures. 2. Mixtures of oleic
      acid with lauric acid, myristic acid, and palmitic acid.
AB  - Solid-liquid phase behavior was investigated for binary fatty acid mixtures
      composed of oleic acid (OA; cis-9-octadecenoic acid) and saturated fatty acids,
      lauric acid (LA; dodecanoic acid), myristic acid (MA; tetradecanoic acid), and
      palmitic acid (PA; hexadecanoic acid), by means of differential scanning
      calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). When the
      mixture was heated immediately after the solidification from the melt, the heat
      effect due to the gamma-to-alpha transformation of OA varied depending on the
      composition of the mixture. However, the mixture subjected to an annealing at the
      temperature slightly below the melting temperature provided the transformation at
      constant temperature which corresponds to the gamma-to-alpha transformation
      temperature of pure OA. This suggests that a solid phase formed by cooling of the
      melt of the mixture is not in an equilibrium state, but it relaxes to a stable
      solid during the annealing process. The T-X phase diagrams of these mixtures
      constructed from the DSC measurements demonstrate that the two fatty acid species
      are completely immiscible in a solid phase regardless of the type of polymorphs
      of OA, alpha- or gamma-form. According to a thermodynamic analysis of liquidus
      line basing on the regular solution model for the melt, the non-ideality of
      mixing tends to increase with the decrease in the acyl chain length of the
      saturated fatty acid, although the mixing is rather close to ideal.

PMID- 14726000
TI  - Insights on the interaction of met-enkephalin with negatively charged membranes-
      an infrared and solid-state NMR spectroscopic study.
AB  - Enkephalins are pentapeptides found in the human nervous system, where they are
      involved in the relief of pain. The interaction of these neuropeptides with the
      nerve cell membranes would be a key-step in the receptor binding. We have used
      both Fourier-transform infrared and solid-state NMR spectroscopies to shed light
      on the interactions responsible for the association of enkephalins with
      negatively charged membranes. More specifically, we have investigated the
      interaction of methionine-enkephalin (Menk) with DMPG and DMPS vesicles. Our
      results suggest that Menk interacts electrostatically with both model membranes
      via its terminal NH3+ group. However, the peptide induced the formation of
      elongated DMPG vesicles in the magnetic field. On the other hand, the association
      of Menk with DMPS bilayers was concentration-dependent and disrupted the membrane
      at high peptide concentrations. The different effect of methionine-enkephalin
      with the two types of anionic membranes is most likely related to the different
      fluidity of these systems.

PMID- 14726001
TI  - Photoinduced interaction of riboflavin dye with different reducing agents in
      aqueous and liposome media.
AB  - The photoelectrochemical and spectral studies of riboflavin have been carried out
      in aqueous and phosphatidylcholine (PC) liposome media in presence of different
      reducing agents such as I-, Br-, Cl-, Fe2+, Fe(CN)6(4-) and Cu+. The results from
      both the studies support the photoinduced electron transfer from the reducing
      agent to the excited riboflavin dye. Moreover, a good correlation between
      photovoltages/Stern-Volmer quenching constants versus reduction potentials of the
      reducing agents also confirms the above electron transfer in the photoexcited
      state. An alternative method has been developed to determine the Stern-Volmer
      quenching constant.

PMID- 14726002
TI  - Effects of lysophosphatidic acid on melanogenesis.
AB  - In this study, we investigated the effects of lysophosphatidic acid (LPA) on
      melanogenesis in Mel-Ab cells. We found that LPA significantly attenuates melanin
      synthesis, and reduces the activity of tyrosinase, the rate-limiting melanogenic
      enzyme. Interestingly, LPA was also found to induce the activation of a 90 kDa
      ribosomal S6 kinase (RSK-1), which is known to phosphorylate microphthalmia
      associated transcription factor (MITF) at serine 409. Though it has been
      previously reported that the phosphorylation of MITF is followed by the
      degradation of MITF, we found that LPA significantly inhibited MITF promoter
      activity, and that this reduced MITF and tyrosinase protein production. Our
      results indicate that LPA contributes to reduced melanin synthesis via the down
      regulation of MITF.

PMID- 14726003
TI  - Strategies and performance in hospitals.
AB  - Today, more than ever in the past, the variables within the health care
      environment (demand, costs, system deregulation) are undergoing such rapid change
      that hospital administrators are finding it necessary to develop and implement
      competitive strategies in order to survive in the increasingly competitive
      hospital environment. The primary aim of this paper is to answer the following
      question: Is it possible to transfer strategic management research from other
      sectors into the hospital industry? The first objective was to identify
      strategies in hospital management. A questionnaire was designed and sent to
      hospital CEOs and the data extracted were used to construct the variables needed
      to identify strategies and perform the subsequent analyses. The second aim was to
      try to identify groups of organizations using similar strategies and, finally,
      analyse the impact of these on hospital performance.

PMID- 14726004
TI  - The policy analysis of 'values talk': lessons from Canadian health reform.
AB  - Despite widespread recognition of the importance of values, decision makers and
      stakeholders in health policy appear to disagree fundamentally over what 'values'
      essentially are. Hidden dissent about the nature of values can confuse policy
      deliberations. This study investigates empirically the following two questions:
      (1) what sorts of entities do Canadian health reformers typically call 'values'?
      and; (2) how do Canadian health reformers use the idea of values in health reform
      rhetoric? We conducted a qualitative, interpretive analysis of 36 Canadian health
      reform documents published during the period 1990-1999. The values raised in
      Canadian health reform rhetoric vary widely not only in topic (e.g. health
      states, health services, equity, economic viability, etc.) but also in substance
      (e.g. physical entities, goals, principles, attitudes, etc.). We review the
      diversity of concepts underlying 'values talk' in health policy, and discuss
      implications for policy analysis and future research.

PMID- 14726005
TI  - County level responses to the introduction of DRG rates for "extended choice"
      hospital patients in Denmark.
AB  - Choice of hospitals is being discussed in a number of European health systems.
      The Danish case provides interesting lessons because patients' free choice has
      been in effect since 1993. This paper explores the responses at the supply side
      after the introduction of DRG rates for extended choice patients in the Danish
      hospital system in 2000. The main question is whether the introduction of DRG
      rates and the resulting changes in incentives have affected county management of
      health care. How has the county-based governance system, which traditionally has
      emphasised budget control, co-operation and equity, reacted to the introduction
      of DRG rates and stronger incentives for "extended choice patients"?

PMID- 14726006
TI  - Petro-state constraints on health policy: guidelines for workable reform in
      Venezuela.
AB  - This article reviews the performance of the Venezuelan health care sector and
      suggests guidelines for workable health policy under difficult conditions. Two
      special circumstances constrain policy options. First, Venezuelans share a
      traditional value, solidarity, which includes a strong desire for equity. Reforms
      must comply with this norm to succeed. Second, foreign sales of state-controlled
      oil constitute the bulk of the government budget and the gross domestic product
      (GDP). Petroleum market fluctuations expose the country to extreme economic
      cycles. In response, policy making and stakeholders adopt a rentier attitude,
      focusing on preserving or enlarging entitlements to government oil monies. The
      side effects of this largesse include poor productivity, a weak private sector, a
      widespread sense of entitlement without accountability, and a crippled state
      which controls most of the available resources yet is unable to effectively tax,
      regulate, steer the economy, or pursue long-term policies. The health care sector
      shares these problems. As a result, Venezuela's health systems are fragmented,
      poorly coordinated, excessively centralized, inequitable, and ineffective.
      Policies to improve public health and public and private medical care must take
      into account these constraints.

PMID- 14726007
TI  - The impact of ageing on hospital care and long-term care--the example of Germany.
AB  - BACKGROUND: In the next few decades the population in all EU-countries will age
      rapidly. This could have a major impact on the health care sector. This study
      analyses the effect of population ageing on utilisation in two key sectors of the
      health care system, namely hospital care and long-term care in Germany, up to
      2020 with an outlook to 2050. METHODS: Two population scenarios, one with
      constant, one with increasing life expectancy, were combined with constant age
      and gender specific utilisation rates of hospital and long-term care. In the case
      of hospital care two projection methods were used: Method A differentiates
      between age-groups, gender and main diagnosis. Method B differentiates between
      age-groups, survivors and decedents. RESULTS: Population ageing was found to
      cause a moderate increase in hospital days, but was associated with substantial
      changes in the disease and age structure. In the case of increasing life
      expectancy, method B lead to a lower growth in hospital days than method A. The
      number of persons receiving long-term care will increase strongly, associated
      with a shift to more severe disability and institutional care. Changes in the
      composition of private households and the increasing labour participation of
      women will lead to additional demand for professional caregivers at home and in
      institutions. CONCLUSIONS: Changes in the number and disease structure of
      hospital days due to population ageing will require reorganisation and
      restructuring of hospital departments. In the case of long-term care a high
      increase in professional home care and institutional care will be required.
      Health policy has to take into account these developments in order to adequately
      deal with future demand for these services.

PMID- 14726008
TI  - Co-payments in the Austrian social health insurance system. Analysing patient
      behaviour and patients' views on the effects of co-payments.
AB  - Austrian health politicians constantly claim that patients have to be the focus
      of interest when providing health care services. However, due to increasing
      demand, scarce resources and insufficient guidance for health care provision at
      the national level, Austrian patients have been confronted with a variety of
      health care reforms during recent years. These reforms include the introduction
      of additional, mainly lump sum co-payments and the increase of existing (lump
      sum) co-payments. Using a sample of 378 socially-insured patients, the aim of
      this study is to analyse patients' attitudes towards co-payments, their views on
      the effects of co-payments on health care demand and their actual behaviour in
      response to co-payments. The study is descriptive rather than hypothesis testing
      due to the limited data. The results of this survey indicate that co-payments
      have no major guiding effect on health care demand. This is confirmed by what the
      patients indicate as regards their actual behaviour.

PMID- 14726009
TI  - Patient care seeking barriers and tuberculosis programme reform: a qualitative
      study.
AB  - The patient's perspective, including his/her socio-economic and cultural
      environment, is an important consideration for tuberculosis control programmes.
      Through semi-structured interviews, this qualitative research studies the
      barriers to successful care seeking faced by 202 adult patients with pulmonary
      tuberculosis in urban Zambia. Three common, interdependent themes explain patient
      barriers to successful care seeking: (1) number of health care encounters and
      duration of illness prior to diagnosis; (2) existing financial constraints and
      additional unrecognized patient costs; and (3) travel distances. On average,
      patients have 6.7 health care encounters prior to being diagnosed with
      tuberculosis. Within a resource-poor setting, patients face financial constraints
      and unrecognized costs associated with their illness. Specifically, travel
      distances and related transportation costs create a significant burden on
      patients. In addition, 'special food' expenditures add to their financial
      constraints. The implications of these patient barriers from this study are then
      discussed in the context of three tuberculosis programme reforms occurring in sub
      Saharan Africa: (1) decentralization of tuberculosis services; (2) integration of
      tuberculosis and other services; and (3) evaluation of diagnostic techniques. The
      patient's perspective and related care seeking barriers should be considered in
      reviewing existing tuberculosis programmes and policy, evaluating potential
      programme reform and assessing new tuberculosis interventions.

PMID- 14726010
TI  - Prescription of technical aids by general practitioners in the Netherlands.
AB  - This study focused on the allocation of technical aids, in particular which
      technical aids general practitioners (GPs) prescribe for what patients. Data was
      collected by 64 Dutch GPs participating in a nationwide representative sentinel
      practice network. The GPs gathered information on type of technical aid
      prescribed, patient characteristics, and diagnosis (coded according to the
      International Classification of Primary Care (ICPC)). The most frequently
      prescribed technical aids include incontinence supplies, anti-oedema stockings,
      and rollators. The number of prescribed technical aids increased strongly with
      the age of the patients and almost all technical aids were prescribed more often
      for women than for men. Most technical aids were prescribed based on the
      initiative of the patients. The GPs made a wide range of diagnoses in the
      prescription of technical aids. Diagnoses involving the musculoskeletal system,
      the circulatory system, and the urinary system were the most frequently made.
      Implications of these findings for policy and further research are discussed.

PMID- 14726011
TI  - DNA repair pathways and associated human diseases.

PMID- 14726012
TI  - Four decades of DNA repair: from early insights to current perspectives.
AB  - A brief history of the evolution of the DNA repair field over the past four
      decades is presented, as documented through the Proceedings from a selected
      series of five scientific meetings, beginning with the 1965 Radiation
      Microbiology Conference, held at the University of Chicago with only 40
      participants, and extending through the 1988 UCLA Symposium on "Mechanisms and
      Consequences of DNA Damage Processing", convened in Taos, New Mexico, with over
      400 participants. The published proceedings and recorded discussions from these
      early conferences contain notable insights, of which many have turned out to be
      remarkably clairvoyant while others must be reevaluated in light of recent
      discoveries and developments in the field.

PMID- 14726013
TI  - The base excision repair: mechanisms and its relevance for cancer susceptibility.
AB  - Base damage or loss occurs at high frequency in the cells (almost 10(4) bases are
      damaged and hydrolysed per cell per day). DNA repair is fundamental to maintain
      genomic integrity. Base excision repair (BER) is the main mechanism by which
      cells correct various types of damaged DNA bases generated either by endogenous
      or exogenous factors. The widely accepted model for BER mechanism involves five
      sequential reactions: (i) base removal; (ii) incision of the resulting abasic
      site; (iii) processing of the generated termini at the strand break; (iv) DNA
      synthesis, and (v) ligation. In this review, we will briefly summarise the
      biochemistry of each BER step and will concentrate on the biological relevance of
      BER as inferred from in vitro and in vivo studies. This information will be the
      basis for speculation on the potential role of malfunction of BER in human
      pathology.

PMID- 14726014
TI  - Transcription-coupled repair of 8-oxoguanine in human cells and its deficiency in
      some DNA repair diseases.
AB  - 8-Oxoguanine (8-oxoG) is a major oxidized base found in DNA due to endogenous or
      exogenous pro-oxidant agents. In the absence of repair, this lesion has a high
      mutation potency giving rise mainly to G:C to A:T transversions. 8-oxoG can be
      removed by the classical base excision repair pathway but can also be eliminated
      by a transcription-coupled repair (TCR) process that needs the wild type
      activities of CSB, XPG, XPB, XPD, BRCA1, BRCA2 and MSH2 proteins. The lack of TCR
      of oxidative lesions may lead to dramatic hereditary diseases like Cockayne
      syndrome. Accumulation of unrepaired oxidized bases in brain cells may explain
      the progressive neurological deterioration found in some DNA repair-deficient
      patients.

PMID- 14726015
TI  - The eukaryotic nucleotide excision repair pathway.
AB  - Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair,
      recognizing and dealing with a variety of helix-distorting lesions, such as the
      UV-induced photoproducts cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4
      pyrimidone photoproducts (6-4 PPs). In this review, we describe the main protein
      players and the different sequential steps of the eukaryotic NER mechanism in
      human cells, from lesion recognition to damage removal and DNA synthesis. Studies
      on the dynamics of protein access to the damaged site, and the kinetics of lesion
      removal contribute to the knowledge of how the cells respond to genetic insult.
      DNA lesions as well as NER factors themselves are also implicated in changes in
      cell metabolism, influencing cell cycle progression or arrest, apoptosis and
      genetic instability. These changes are related to increased mutagenesis and
      carcinogenesis. Finally, the recent collection of genomic data allows one to
      recognize the high conservation and the evolution of eukaryotic NER. The
      distribution of NER orthologues in different organisms, from archaea to the
      metazoa, displays challenging observations. Some of NER proteins are widespread
      in nature, probably representing ancient DNA repair proteins, which are
      candidates to participate in a primitive NER mechanism.

PMID- 14726016
TI  - DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and
      trichothiodystrophy.
AB  - Xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD)
      are genetic disorders with very different clinical features, but all associated
      with defects in nucleotide excision repair. Defects in the XPA or XPC genes
      confer sensitivity to UV carcinogenesis in both humans and mice, but only XPA(-/
      ) mice have increased acute responses to UV exposure, whereas XPC(-/-) mice are
      normal in this respect. Both XPE and XPF proteins have functions separate from
      their role in NER, but the exact nature of these functions has not yet been
      established. The CSA and CSB genes responsible for CS are both components of
      complexes associated with RNA polymerase II and their role is thought to be in
      assisting polII in dealing with transcription blocks. XPB and XPD proteins are
      components of transcription factor TFIIH, which is involved in both basal and
      activated transcription. XPB is part of the core of TFIIH and has a central role
      in transcription, whereas XPD connects the core to the CAK subcomplex, and can
      tolerate many different mutations. Subtle differences in the effects of these
      different mutations on the many activities of TFIIH and on its stability
      determine the clinical outcomes, which can be XP, TTD, XP with CS, XP with TTD or
      COFS. Features of single and double mutant mice indicate that the neurological
      and ageing features associated with these disorders result from the defects in
      NER in association with the transcriptional deficiencies. Skin tumours in XP
      patients have mutations characteristic of UV-induction in the ras, p53 and ptch
      genes, showing that sunlight-induced mutations in these genes are important in
      carcinogenesis in XP patients.

PMID- 14726017
TI  - The XPG story.
AB  - I provide a personal account of the discovery, cloning and functional analyses of
      the human XPG gene. Mutations in this gene can give rise to the group G form of
      xeroderma pigmentosum (XP) and, in some cases, to severe early onset Cockayne
      syndrome (CS). The XPG protein has well established catalytic and structural
      roles in nucleotide excision repair (NER) and it acts as a cofactor for a DNA
      glycosylase that removes oxidised pyrimidines from DNA. XPG may also be involved
      in transcription-coupled repair of this kind of damage, in transcription by RNA
      polymerase II, and perhaps in other processes too. Our current knowledge of this
      important protein is largely based on some excellent, highly focussed science.
      But good luck, serendipity and scientific scandal have also made major
      contributions to this unfinished story.

PMID- 14726018
TI  - Xeroderma pigmentosum variant and error-prone DNA polymerases.
AB  - Replicative DNA synthesis is a faithful event which requires undamaged DNA and
      high fidelity DNA polymerases. If unrepaired damage remains in the template DNA
      during replication, specialised low fidelity DNA polymerases synthesises DNA past
      lesions (translesion synthesis, TLS). Current evidence suggests that the
      polymerase switch from replicative to translesion polymerases might be mediated
      by post-translational modifications involving ubiquitination processes. One of
      these TLS polymerases, polymerase eta carries out TLS past UV photoproducts and
      is deficient in the variant form of xeroderma pigmentosum (XP-V). The dramatic
      proneness to skin cancer of XP-V individuals highlights the importance of this
      DNA polymerase in cancer avoidance. The UV hypermutability of XP-V cells suggests
      that, in the absence of a functional poleta, UV-induced lesions are bypassed by
      inaccurate DNA polymerase(s) which remain to be identified.

PMID- 14726019
TI  - Repairing DNA damage in chromatin.
AB  - Understanding how DNA repair processes occur in vivo when access to DNA is
      hindered by chromatin structural organisation is a current challenge. In general
      terms, the following sequence of events has to be considered within a chromatin
      environment: (i) finding a lesion (ii) repairing this lesion, and (iii) full
      restoration of a functional chromatin locus. In this review, basic principles
      concerning nucleosome dynamics, both intrinsic properties and those dependent on
      accessory factors, will be used to discuss the issue of lesion accessibility to
      damage-detecting proteins within chromatin. In addition, opportunities for damage
      detection due to chromatin alterations directly linked with transcription and
      replication processes will be considered. After damage detection, additional
      processes to enhance accessibility within chromatin may be needed to accommodate
      downstream repair factors or to allow DNA synthesis, resulting in interdependency
      between repair and accessibility mechanisms in chromatin. Finally, we will
      comment on the way in which chromatin assembly factors can participate in the
      maintenance of chromatin structures during DNA repair.

PMID- 14726020
TI  - Human mismatch repair, drug-induced DNA damage, and secondary cancer.
AB  - DNA mismatch repair (MMR) is an important replication error avoidance mechanism
      that prevents mutation. The association of defective MMR with familial and
      sporadic gastrointestinal and endometrial cancer has been acknowledged for some
      years. More recently, it has become apparent that MMR defects are common in acute
      myeloid leukaemia/myelodysplastic syndrome (AML/MDS) that follows successful
      chemotherapy for a primary malignancy. Therapy-related haematological
      malignancies are often associated with treatment with alkylating agents. Their
      frequency is increasing and they now account for at least 10% of all AML cases.
      There is also evidence for an association between MMR deficient AML/MDS and
      immunosuppressive treatment with thiopurine drugs. Here we review how MMR
      interacts with alkylating agent and thiopurine-induced DNA damage and suggest
      possible ways in which MMR defects may arise in therapy-related AML/MDS.

PMID- 14726021
TI  - Repair of DNA double strand breaks by non-homologous end joining.
AB  - DNA double strand breaks (DSB) are the most serious form of DNA damage. If not
      repaired they can lead to cell death. If misrepaired DSBs contribute to
      chromosomal aberrations and genomic instability. Non-homologous end joining
      (NHEJ) is one of two major pathways for the repair of DSBs in human cells.
      Proteins known to be required for NHEJ include the DNA-dependent protein kinase
      (DNA-PK), XRCC4, DNA ligase IV, and Artemis. This review discusses how these and
      other accessory proteins may function in the repair of DSBs produced by ionizing
      radiation (IR) and by V(D)J recombination.

PMID- 14726022
TI  - The Fanconi anemia pathway and the DNA interstrand cross-links repair.
AB  - Fanconi anemia (FA) is a genetic cancer-predisposition syndrome characterized by
      bone marrow failure and cellular and chromosomal hypersensitivity to DNA cross
      linking agents. Seven FA genes have been isolated and their products associate to
      form a pathway that interacts functionally or physically with several DNA-damage
      response proteins involved in cell cycle checkpoints and/or DNA repair. These
      proteins include BLM, ATM, BRCA1, XPF and the MRE11/RAD50/NBS1 complex. In spite
      of several recent striking progresses in the biochemistry and the molecular
      biology of the disorder, the precise function(s) of the FA proteins remain(s)
      poorly determined. However, several recent data indicate that the FA pathway
      could be involved in the coordination of both cell cycle checkpoints and DNA
      repair.

PMID- 14726023
TI  - Human diseases deficient in RecQ helicases.
AB  - RecQ helicases are conserved from bacteria to man. Mutations in three of the
      human RecQ family members give rise to genetic disorders characterized by genomic
      instability and a predisposition to cancer. RecQ helicases are therefore
      caretakers of the genome, and although they do not directly regulate
      tumorigenesis, they influence stability and the rate of accumulation of genetic
      alterations, which in turn, result in tumorigenesis. Maintenance of genome
      stability by RecQ helicases likely involves their participation in DNA
      replication, recombination, and repair pathways.

PMID- 14726025
TI  - A gift from anonymous.

PMID- 14726026
TI  - Implementing the ACGME general competencies in a cardiothoracic surgery residency
      program using 360-degree feedback.
AB  - BACKGROUND: Methods to assess the six competency categories outlined by the
      Accreditation Council on Graduate Medical Education are essential to allow
      residency programs to develop reproducible evaluations of their educational
      curriculum. Current tools to evaluate competencies are insufficient to perform
      these tasks, particularly in subspecialty disciplines. The key objective of this
      initiative was to develop and implement an evaluative tool that would provide
      data to residents and program leadership regarding their performance and to
      provide the training program with a reliable way to assess this component of the
      program. METHODS: Utilizing a highly customized survey tool with a group of
      cardiothoracic residents, we implemented a 360-degree performance assessment
      process based on the six Accreditation Council on Graduate Medical Education
      competency areas. The full spectrum of associations in a resident's sphere of
      interaction were surveyed (ie, supervisors, peers, direct reports, nurses, and
      administrative personnel). Each resident received a comprehensive report that
      included detailed documentation of the self-evaluation and the average rating of
      others by category. Each resident also received a transcript of the responses to
      the open-ended questions and summary of the data highlighting areas of
      excellence, areas for improvement, and suggested goals and recommendations. The
      program director received copies of all of these as well as a chart documenting
      the average scores on each item for the whole cohort. RESULTS: Each resident met
      with the 360-degree feedback specialist and the program director to develop and
      commit to an action plan based on the feedback. The feedback process was repeated
      approximately 8 months later. CONCLUSIONS: The 360-degree feedback results
      provided valuable information for the residents. It also provided our program
      with a reproducible, quantifiable tool to assess these competencies. Combined
      with other instruments, the 360-degree feedback was found to be a particularly
      valuable instrument.

PMID- 14726027
TI  - Routine mechanical ventricular assist following the Norwood procedure--improved
      neurologic outcome and excellent hospital survival.
AB  - BACKGROUND: Although excellent survival following the Norwood procedure for
      palliation of hypoplastic left heart syndrome (HLHS) is being achieved by some,
      most centers, especially the ones with small surgical volume and limited
      experience, continue to struggle with initial results. Survivors often showed
      evidence of significant neurologic injury. The early postoperative care is labor
      intensive as attempts are made to balance the systemic and pulmonary circulation
      for these infants. We report our experience with routine use of mechanical
      circulatory assist to support the increased cardiac output requirements present
      following Norwood procedure. METHODS: Eighteen consecutive infants undergoing
      Norwood operation for HLHS (Oregon Health & Science University [OHSU] 13;
      University of Louisville [UL] 5) were placed on a ventricular assist device (VAD)
      immediately following modified ultrafiltration in the operating room using the
      cardiopulmonary bypass (CPB) cannulas that were in the right atrium and the
      neoaorta. VAD flows were maintained at approximately 200 mL x kg(-1) x min(-1)
      and the patients were transported to the intensive care unit (ICU). Patients
      operated at OHSU also received neurodevelopmental testing before their Glenn
      procedure, approximately 4 to 6 months following their Norwood operation.
      RESULTS: All patients were stable on VAD support and no attempt was made to
      balance the systemic and pulmonary circulation. The ventilator was manipulated to
      achieve systemic Pa0(2) between 30 and 45 mm Hg and PaC0(2) between 35 and 45 mm
      Hg. Evidence of hypoperfusion (increasing lactates) was managed by increasing the
      VAD flow. Lactates normalized [< 2 mmol/L]) by 1.8 +/- 1.1 days following
      surgery. Average time of VAD support was 3.1 +/- 1.0 (range, 2 to 5 days) and
      average time until chest closure was 3.4 +/- 1.5 (range, 2 to 8 days). There were
      two cases of postoperative bleeding (11.1%) requiring reexploration and one case
      of mediastinitis (5.5%) in a patient who has now gone on to successful Glenn.
      Sixteen of the eighteen patients survived (hospital survival mean 89% with a 95%
      confidence interval of 63.9% to 98.1%; 12/13 OHSU [92.3%]; 4/5 UL [80%]).
      Neurodevelopmental testing using the Mullen Scales of Early Learning and the
      Vineland Adaptive Behavior Scale were normal for all infants tested. CONCLUSIONS:
      Routine postoperative use of VAD can support the increased cardiac output demands
      of infants following Norwood operation and results in a stable postoperative
      convalescence that does not require aggressive ventilator or inotrope
      manipulation. Although not a panacea, this strategy can simplify postoperative
      management, lead to excellent hospital survival, and possibly augment cerebral
      oxygen delivery, resulting in improved neurologic outcomes for this challenging
      group of patients.

PMID- 14726028
TI  - Management of univentricular heart with systemic ventricular outflow obstruction
      by pulmonary artery banding and Damus-Kaye-Stansel operation.
AB  - BACKGROUND: Some patients with univentricular hearts who are candidates for
      Fontan operation may develop ventricular outflow tract obstruction after
      pulmonary artery banding (PAB) or Fontan. However, the indication for Damus-Kaye
      Stansel (DKS) operation for these patients has not been clear. To clarify the
      indication, the changes in the diameter of ventricular outflow tract and the
      feasibility of DKS operation before or with Fontan were investigated. METHODS:
      Among the patients with univentricular heart who underwent PAB, 21 patients had
      probable ventricular outflow obstruction with an aorta arising from the
      morphologic right ventricle. Diameter of ventricular outflow tract was measured
      before and after PAB, Glenn, and Fontan operations with or without DKS, and
      indexed by normal value (%VOT). RESULTS: Six patients died after PAB. In the
      surviving 15 patients, %VOT decreased significantly from 103% (median, range 75%
      153%) to 75% (range 52%-153%) after PAB. Four with very small %VOT (52% to 63%)
      after PAB needed DKS with bidirectional Glenn or central shunt operation, and 5
      with moderately small %VOT (67% to 109%) after PAB needed DKS concomitantly with
      Fontan. A patient with %VOT of 117% before Fontan required DKS after Fontan. A
      patient with %VOT of 153% underwent Fontan without DKS and obstruction did not
      develop after Fontan. The remaining 4 patients were under consideration for Glenn
      or Fontan operation. CONCLUSIONS: The diameter of the ventricular outflow tract
      decreased after PAB and Fontan operations. DKS operations might be indicated
      before Fontan if the indexed diameter of ventricular outflow tract after PAB was
      below 70% and concomitantly with Fontan if it was below 120%.

PMID- 14726029
TI  - Successful early surgical recruitment of the congenitally disconnected pulmonary
      artery.
AB  - BACKGROUND: Our purpose was to document our experience with early recruitment of
      congenitally disconnected pulmonary arteries and to assess subsequent pulmonary
      artery growth and function. METHODS: Patients born in the 10-year period from
      1989 to 1999 with a disconnected pulmonary artery diagnosed in infancy and
      treated in our unit were studied. To be included patients had nonconfluent
      pulmonary arteries with one or both completely disconnected from the main
      pulmonary artery. This series did not include patients with acquired stenosis
      causing occlusion of a pulmonary artery. Echocardiography, cardiac
      catheterization, MRI, lung perfusion scans, and intraoperative assessment were
      used to gauge pulmonary artery growth and function. RESULTS: Seven patients with
      a disconnected pulmonary artery associated with intracardiac conotruncal
      congenital cardiac disease underwent successful early surgical recruitment of the
      affected pulmonary artery at 3 months of age or younger. Median follow-up from
      date of first operation was 4.2 years (range, 1.6 to 13.4). All 7 patients had
      postrecruitment lung perfusion scans showing a mean of 44% (range, 27% to 78%) of
      total pulmonary flow through the affected lung. Significant growth in the
      diameter of the recruited native pulmonary artery was demonstrated in all
      patients. There were no deaths reported in our series to date. CONCLUSIONS: The
      rare possibility of a congenitally disconnected pulmonary artery needs to be
      considered in all patients with a conotruncal cardiac anomaly. To facilitate
      surgical correction, ensure subsequent growth of the pulmonary artery, and
      optimize associated lung development, early diagnosis and surgical recruitment is
      recommended.

PMID- 14726030
TI  - The fibrous matrix of ventricular myocardium in hypoplastic left heart syndrome:
      a quantitative and qualitative analysis.
AB  - BACKGROUND: Controversy exists as to whether the right ventricle will be able to
      cope as the sole pumping chamber following a univentricular repair of hypoplastic
      left heart syndrome. The significance of the collagenous matrix on ventricular
      function has been studied extensively yet there is little information available
      on its quantity and quality in hypoplastic left heart syndrome. METHODS: We
      selected 23 specimens with hypoplastic left heart syndrome for anatomical study.
      Using a combination of morphometric analysis and scanning electron microscopy we
      analyzed the quantity and quality of the collagenous matrix. We compared the
      results with 16 age-matched controls. RESULTS: Hearts with hypoplastic left heart
      syndrome have significantly less collagen matrix than normal. The right ventricle
      has more collagen than the left and there is significant transmural variation.
      There was no difference in the ratio of the two main collagen subtypes or in the
      quality of the matrix. CONCLUSIONS: We believe this difference in fibrous matrix
      to be an inherent abnormality intrinsic to the malformation affecting not only
      the hypoplastic left but also the "normal" right ventricle. This in turn may have
      significant implications for the expected long-term outcome of reconstructive
      surgery.

PMID- 14726031
TI  - Results of arterial switch operation for primary total correction of the Taussig
      Bing anomaly.
AB  - BACKGROUND: This study evaluates the results of the arterial switch operation for
      early total repair of double-outlet right ventricle with subpulmonary ventricular
      septal defect (the Taussig-Bing heart). METHODS: From 1986 through April 2003, 27
      patients with Taussig-Bing anomaly underwent arterial switch operation. Twenty
      patients were neonates (n = 11) or infants younger than 3 months (n = 9).
      Obstruction of aortic arch (n = 19) or subaortic right ventricular outflow tract
      obstruction (n = 20) and unusual coronary artery patterns (n = 19) were common.
      Total correction as a single procedure was performed in 21 patients. Events are
      depicted by Kaplan-Meier curves. RESULTS: There was 1 patient hospital death at 2
      months after repair. One patient died late that was not cardiac related. Survival
      was 92% +/- 6% at 8 months and remained constant thereafter. Four patients
      underwent reoperation (1 for residual aortic arch obstruction and 3 for
      subvalvular and valvular pulmonary stenosis). Freedom from reoperation decreased
      to stabilize at 83% +/- 8% after 2 years. The risk to have right ventricular
      outflow tract obstruction develop was 33% +/- 10% at 1 year, increasing slowly
      and leveling out at 57% +/- 12% at year 5 and thereafter. Statistical analysis
      revealed no significant risk factor for death or need for reoperation.
      CONCLUSIONS: The Taussig-Bing anomaly should be corrected in the neonatal period
      or in early infancy by arterial switch operation, closure of the ventricular
      septal defect, and simultaneous correction of associated cardiovascular anomalies
      as a one-stage procedure. Right ventricular outflow tract obstruction often
      complicates the postoperative course and is the main cause for reintervention.

PMID- 14726033
TI  - High systemic vascular resistance and sudden cardiovascular collapse in
      recovering Norwood patients.
AB  - BACKGROUND: Sudden death, remote from surgery, in patients with hypoplastic left
      heart syndrome (HLHS) after Norwood palliation is an important problem. The
      episodic nature of this syndrome has made its cause(s) difficult to ascertain.
      Observations made in hospitalized Norwood patients may afford insight into the
      pathophysiology of sudden death among these patients. METHODS: We conducted a
      retrospective chart review. RESULTS: Five patients with HLHS experiencing
      unremarkable recoveries from Norwood palliation, still hospitalized but extubated
      (only 1 in intensive care), had unexpected, acute decompensation 8 to 15 days
      postoperatively. All had acutely decreased peripheral perfusion; severe metabolic
      acidosis (mean HCO(3) = 9 mEq/L, range 6 to 11 mEq/L; mean arterial lactate = 16
      mmol/L, range 10 to 20 mmol/L, normal less than 2 mmol/L); relatively high
      arterial pO(2), especially considering their low systemic perfusion (mean = 57 mm
      Hg, range 50 to 66 mm Hg on fraction of inspired oxygen (FiO(2)) less than 0.3 in
      4 of 5 patients); and relatively high systolic blood pressure (mean systolic
      blood pressure = 91 mm Hg, range 78 to 116 mm Hg). During the preceding 24 hours,
      all had had systolic blood pressures of more than 85 mm Hg at multiple times. All
      were resuscitated with mechanical ventilation and administration of HCO(3) and
      intravenous inotropic agents or vasodilators (1 also required extracorporeal
      membrane oxygenation), with rapid resolution of their acidosis. After
      decompensating, all were treated with oral antihypertensive agents; 1 had an
      early hemi-Fontan. All survived to discharge. CONCLUSIONS: Increased systemic
      vascular resistance may be especially pernicious in Norwood patients-even remote
      from operation-as the condition increases myocardial work and O(2) consumption
      while diminishing systemic perfusion. Chronic and acutely increased systemic
      vascular resistance may account for some cases of sudden unexpected death in
      Norwood patients.

PMID- 14726034
TI  - Echocardiographic analysis of ventricular geometry and function during repair of
      congenital septal defects.
AB  - BACKGROUND: This study investigated changes in left ventricular (LV) geometry and
      systolic function after corrective surgery for atrial (ASD) and ventricular
      septal defects (VSD). METHODS: Transesophageal LV short-axis echocardiograms were
      recorded before and after operative repair of ASD (n = 11) and VSD (n = 7).
      Preload was measured using LV end-diastolic area indexed for body surface area.
      Measurements of septal-freewall (D1) and anterior-posterior (D2) endocardial
      diameters were used to assess LV symmetry from D1/D2. Systolic indices included
      stroke area, area ejection fraction, and fractional shortening. RESULTS: Preload,
      stroke area, area ejection fraction, and fractional shortening of D1 increased
      after ASD repair but decreased after VSD repair (p < 0.05). End-diastolic
      symmetry increased after ASD closure and decreased after VSD closure (p < 0.05).
      Increases in stroke area and ejection fraction after ASD correction primarily
      reflected increased shortening of D1. A positive correlation was found overall
      between percent change in end-diastolic area (EDA) and percent change in area
      ejection fraction (r(2) = 0.80, p < 0.0001, n = 18). CONCLUSIONS: Preload was the
      primary determinant of changes in LV function in this series of ASD and VSD
      repairs. Intraoperative changes in position of the interventricular septum
      affected systolic and diastolic LV symmetry and septal free wall shortening.
      Additional studies are needed to define changes in afterload and contractility as
      well as diastolic compliance and systolic mechanics.

PMID- 14726035
TI  - Predictors of mortality at initiation of peritoneal dialysis in children after
      cardiac surgery.
AB  - BACKGROUND: The development of renal dysfunction in the postoperative course of
      cardiac surgery is still associated with high mortality in pediatric patients. In
      particular for small infants peritoneal dialysis offers a secure and useful
      treatment option. The aim of the present study was to investigate if routinely
      used laboratory and clinical variables could help predict mortality at initiation
      of peritoneal dialysis. METHODS: We performed a retrospective chart analysis of
      pediatric intensive care unit patients with renal dysfunction who were treated
      with peritoneal dialysis after cardiac surgery between 1993 and 2001 and analyzed
      variables obtained 3 hours or less before starting peritoneal dialysis. RESULTS:
      Results are documented as means and standard errors. A total of 1141 children
      underwent a cardiac operation on cardiopulmonary bypass. Sixty-two children
      (5.4%) were treated with peritoneal dialysis. Mortality was 40.3% (37 survivors,
      25 nonsurvivors). The pH in survivors was 7.35 (0.01); in nonsurvivors it was
      7.23 (0.03; p = 0.0037). Base excess in survivors was -1.37 mmol/L (0.61); in
      nonsurvivors it was -7.17 mmol/L (1.49; p = 0.0026). Lactate in survivors was 4.5
      mmol/L (0.60); in nonsurvivors it was 10.5 mmol/L (1.78; p = 0.0089). Positive
      inspiratory pressure in survivors was 24.6 cm H(2)O (0.78); in nonsurvivors it
      was 28.9 cm H(2)O (1.08; p = 0.0274). Tidal volume per kilogram bodyweight in
      survivors was 11.0 mL/kg (0.48); in nonsurvivors it was 8.7 mL/kg (0.50; p =
      0.0493). CONCLUSIONS: We conclude from our data that the consideration of pH,
      base excess, lactate, positive inspiratory pressure, and tidal volume per
      kilogram bodyweight help predict mortality at initiation of peritoneal dialysis.
      We were able to observe significant differences between survivors and
      nonsurvivors using these variables.

PMID- 14726036
TI  - Early postoperative body temperature and developmental outcome after open heart
      surgery in infants.
AB  - BACKGROUND: Experimental data have suggested that early postoperative temperature
      management after cerebral ischemia may alter neurologic outcome. We explored
      whether minor deviations in early postoperative body temperature after infant
      heart surgery affects developmental outcome. METHODS: In a study of infants
      undergoing repair of congenital heart disease, 95% of whom had a period of deep
      hypothermic circulatory arrest, postoperative temperature data were collected
      following cardiac surgery. Subjects were infants who had been enrolled in one of
      two prospective randomized single-center trials. Development was tested at age
      one year (the Bayley Scales of Infant Development) and at four years (Wechsler
      Preschool and Primary Scale of Intelligence, including Full Scale IQ, a Verbal
      IQ, and a Performance IQ). RESULTS: Perioperative temperature data were reviewed
      in 329 patients, of whom 244 (74%) were evaluated at age one year and 156 (48%)
      were evaluated at four years. The temperature profile was recorded during the
      rewarming phase and for 36 hours postoperatively on the Intensive Care Unit.
      There were no significant associations between postoperative temperature and any
      of the neurodevelopmental tests at age one or four years. A further analysis
      assessing the percentage of time over specific temperature cutoff points of 37.5
      degrees C, 38 degrees C, 38.5 degrees C, and 39 degrees C, revealed no
      significant effect. CONCLUSIONS: Neurodevelopmental outcome at one and four years
      after repair of complex congenital heart disease was not significantly affected
      by the early postoperative body temperature profile of the infant when a
      management strategy aiming for normothermia is employed.

PMID- 14726038
TI  - Cerebral autoregulation after hypothermic circulatory arrest in operations on the
      aortic arch.
AB  - BACKGROUND: The purpose of this study was to determine whether patients who
      undergo thoracic aorta repairs with the aid of hypothermic circulatory arrest
      experience impairments in cerebral autoregulation, and to ascertain the influence
      of three different techniques of cerebral protection on autoregulatory function.
      METHODS: Sixty-seven patients undergoing elective aortic arch procedures with
      hypothermic circulatory arrest were tested for cerebral dynamic autoregulation
      using continuous transcranial Doppler velocity and blood pressure recordings.
      Twenty-three patients were treated using hypothermic circulatory arrest without
      adjuncts (group 1), 25 using antegrade cerebral perfusion (group 2), and 19 using
      retrograde cerebral perfusion (group 3). RESULTS: There were no hospital deaths.
      Two major strokes occurred in this series; 9 patients experienced temporary
      neurologic dysfunction: in all these patients severe impairment of cerebral
      autoregulation was observed. Cerebral autoregulation in the immediate
      postoperative period was preserved only in patients treated with antegrade
      cerebral perfusion. Severe impairments were observed in the other two groups in
      which the degree of autoregulatory response was inversely correlated to the
      duration of the cerebral protection time during hypothermic circulatory arrest.
      Postoperative improvement of autoregulatory function was observed in the majority
      of patients. Our data suggest the exposure to brain damage in the presence of
      autoregulation impairment, thus indicating that postoperative hypotensive phases
      may further contribute to neurologic impairment. CONCLUSIONS: The status of
      cerebral autoregulation in the postoperative period after hypothermic circulatory
      arrest procedures is profoundly altered. The degree of impairment is influenced
      by the cerebral protection technique. This study indicates the beneficial role of
      antegrade perfusion during hypothermic circulatory arrest for the preservation of
      this function and suggests that postoperative cerebral autoregulation impairment
      can be regarded as an expression of central nervous system injury.

PMID- 14726040
TI  - Stent-graft repair of penetrating atherosclerotic ulcers in the descending
      thoracic aorta: mid-term results.
AB  - BACKGROUND: Localized aortic pathoanatomic abnormalities are good targets for
      endovascular stent-grafting but only short-term results have been reported. Our
      objective was to determine the effectiveness of endovascular stent-graft
      treatment of patients with descending thoracic atherosclerotic penetrating
      atherosclerotic ulcers (PAU) and to identify risk factors for treatment failure.
      METHODS: Between 1993 and 2000 endovascular repair of PAU with first-generation
      (custom-fabricated) and second-generation (commercial) stent-grafts was performed
      in 26 patients (mean age, 70 years), 6 (23%) of whom had rupture. Fourteen
      patients (54%) were not candidates for open surgical repair. Follow-up was 100%
      complete (average, 51 months; maximum, 114 months). Outcome variables considered
      in the multivariable analysis included death and treatment failure (composite end
      point comprising early death, endoleak, stent-graft mechanical fault, late aortic
      event, reintervention, and aortic-related or sudden death). RESULTS: Three
      patients (12% +/- 7% [+/-70% confidence limits]) died within 30 days and 2 had an
      early type I endoleak. Primary success rate was 92%. Actuarial survival estimates
      at 1, 3, and 5 years were 85% +/- 8%, 76% +/- 8% and 70% +/- 10% respectively and
      actuarial freedom from treatment failure was 81% +/- 8%, 71% +/- 9% and 65% +/-
      10%. Multivariable analyses identified previous cerebrovascular accident (hazard
      ratio [HR] 17.1, p = 0.02) and female sex (HR 7.4, p = 0.08) as independent risk
      factors for death. For treatment failure the predictors were increasing aortic
      diameter (HR 1.1 [per mm above the mean value], p = 0.01) and female sex (HR 5.5,
      p = 0.09). CONCLUSIONS: Endovascular stent-graft repair is effective but not
      curative treatment for selected, high surgical risk, elderly patients with a
      descending aortic PAU over the medium term. Assiduous serial follow-up imaging
      after stent-grafting is mandatory to detect late complications especially in
      those with a large aorta.

PMID- 14726041
TI  - Cox/Maze III operation versus radiofrequency ablation for the surgical treatment
      of atrial fibrillation: a comparative study.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of
      radiofrequency (RF) ablation in the treatment of atrial fibrillation, by
      comparatively analyzing the outcomes of the patients who underwent RF ablation
      with those of patients who underwent Cox/Maze III surgery. METHODS: Between April
      1995 and June 2002, 70 patients underwent surgery for atrial fibrillation and
      open-heart surgery at the Department of Cardiovascular Surgery of the University
      of Bologna: 30 patients underwent the surgical Cox/Maze III procedure (group 1),
      and 40 patients underwent the RF ablation according to the Maze III configuration
      at least on the left atrium (group 2). There were 14 males and 56 females, with a
      mean age of 61.5 +/- 12.5 years (range 22 to 80 years old). RESULTS: Groups 1 and
      2 did not differ in terms of baseline characteristics. The perioperative
      mortality rate was not significantly different between the two groups (6.6% in
      group 1 vs 7.5% in group 2). The overall cumulative rates of sinus rhythm were
      68.9% in group 1 and 88.5% in group 2 (not statistically significant). Biatrial
      contraction was assessed by transthoracic echocardiography in 70.4% of the
      patients in group 1 and 76.5% of the patients in group 2 (p = 0.65). CONCLUSIONS:
      The RF ablation procedure offers as good results as the Cox/Maze III operation,
      allowing recovery of the sinus rhythm and atrial function in the great majority
      of patients with atrial fibrillation who underwent open heart surgery; it is a
      safe and effective means of curing atrial fibrillation with negligible technical
      and time requirements.

PMID- 14726042
TI  - Patencies of 2127 arterial to coronary conduits over 15 years.
AB  - BACKGROUND: Use of arterial grafts in coronary surgery is based on the excellent
      patency of the left internal thoracic artery (LITA) and an expectation that other
      arterial grafts-right internal thoracic artery (RITA) and radial artery (RA)-will
      give similar patencies, superior to saphenous vein. We examined patencies of
      arterial grafts in a practice with extensive use for more than 15 years. METHODS:
      Consecutive postoperative angiograms of 2,127 arterial/coronary conduits were
      evaluated. Angiograms were performed for cardiac symptoms. Assessment was by two
      observers. String signs were considered as occlusions. RESULTS: There were 2127
      arterial conduits. Overall patencies were as follows: LITA, 96.4% (1296 of 1345);
      RITA, 88.3% (534 of 605); aortocoronary RA, 89.3% (158 of 177). The LITA patency
      to the left anterior descending artery was 97.1% (1131 of 1165); to the obtuse
      marginal artery it was 91.7% (165 of 180; p 0.01). The RITA pedicled graft
      patency was 86% (275 of 321) compared with free RITA, 91% (259 of 284; p = not
      significant). For RITA there was a hierarchy of patency for coronary territory
      grafted (left anterior descending artery best, right coronary/posterior
      descending artery worst) and for degree of coronary stenosis: if stenosis was
      less than 60%, patency was 65% (47 of 72); if stenosis was more than 60%, patency
      was 90.9% (485 of 533; p = 0.0001). Similarly for the radial artery there was
      higher patency with greater coronary stenosis. The LITA patency at 5 years was
      98%, at 10 years it was 95%, and at 15 years it was 88%. The RITA patency at 5
      years was 96%, at 10 years it was 81%, and at 15 years it was 65%. The radial
      artery patency at 1 year was 96% and at 4 years it was 89%. For 3,714 vein grafts
      also studied overall patency was 61% (2266 of 3214) with patencies of 95% at 5
      years, 71% at 10 years, and 32% at 15 years. CONCLUSIONS: Excellent long-term
      patencies of arterial grafts are noted, superior to those of vein grafts.
      Patencies were influenced by conduit, by distribution, and by coronary artery
      stenosis.

PMID- 14726043
TI  - Reduced strokes in the elderly: the benefits of untouched aorta off-pump coronary
      surgery.
AB  - BACKGROUND: Avoiding aortic manipulation during off-pump coronary artery bypass
      (OPCAB) reduces the risk for atheroembolic complications and may, thus, benefit
      elderly patients who are prone to atherosclerotic aortic involvement. METHODS:
      During a period of 18 months (2000-2002), 160 consecutive OPCAB patients older
      than 75 years were evaluated. One hundred and three patients undergoing clampless
      OPCAB were compared to 57 patients in whom side clamps were applied. Clampless
      revascularization was achieved by in situ or T-graft arterial configurations.
      RESULTS: Mean age was older (79.3 years vs 78.2, p = 0.049) and the prevalence
      (43% vs 7%, p < 0.0001) and severity of aortic disease was higher in the
      clampless group. The main conduits used were bilateral skeletonized internal
      thoracic artery (47%) and radial arteries (42%). More grafts were performed in
      the side-clamp group (2.5 +/- 0.5 vs 2.3 +/- 0.6, p = 0.023), however,
      revascularization of the postero-lateral territory was comparable. While early
      mortality (2.9% vs 7%, p = >or=0.05), perioperative myocardial infarction (3% vs
      5%, p = >or=0.05), and sternal infections (none) were similar, the incidence of
      major neurological complications (0% vs 5.3%, p = 0.044) and the combined outcome
      of stroke or mortality (3% vs 12%, p = 0.035) were lower in the clampless group.
      Multivariate analysis identified side clamping as a predictor for the occurrence
      of stroke or mortality (OR, 6.28, CL 1.39-28.4, p = 0.017), increasing this risk
      by sixfold. CONCLUSIONS: Clampless OPCAB is associated with reproducible
      neurological benefit. Improved neurological outcome may be conferred irrespective
      of the method of aortic screening in patients 75 years or older. The use of
      arterial conduits for this purpose is feasible despite the patients' advanced
      years.

PMID- 14726044
TI  - Effect of moderate pressure distention on the human saphenous vein vasomotor
      function.
AB  - BACKGROUND: Manual pressure distension, which is commonly applied to the human
      saphenous vein graft for coronary artery bypass, is believed to have detrimental
      consequences for the graft patency. The vasomotor function of the vein after
      distention during surgical preparation for grafting and after distention in
      laboratory conditions at pressure of 50 to 600 mm Hg was studied. The effect of a
      combination of vasodilative agents to prevent vasospasm was also tested. METHODS:
      The contractile and dilatory responses of distended and undistended human
      saphenous veins and those after drug treatment were examined in organ baths under
      isometric conditions. RESULTS: Distention at the pressure range 100 to 300 mm Hg
      resulted in an increased contractile response of the saphenous vein to both alpha
      adrenergic activation with 50 micromol/L phenylephrine (153.73% +/- 15.69%) and
      depolarization with 80 mmol/L K(+) (141.03% +/- 15.13%) in comparison with the
      undistended vein and did not impair the relaxation. In contrast manual distention
      during surgical preparation abolished the contractile response and impaired the
      relaxation. The application of a combination of vasodilative drugs (alpha
      adrenergic antagonist phenoxybenzamine, 10 micromol/L, Rho-kinase inhibitor HA
      1077, 50 micromol/L, and calcium blocker nicardipine, 1 micromol/L) eliminated
      the contractile response of the vein to phenylephrine and 80 mmol/L K(+). This
      effect was sustained more than 20 hours after the washout of the drugs.
      CONCLUSIONS: The distention of the human saphenous vein at moderate pressure
      combined with the application of the effective combination of vasodilative drugs
      before grafting into the arterial circulation could be a beneficial alternative
      to the current practice of uncontrolled pressure distension.

PMID- 14726046
TI  - Duplex ultrasonography predicts safety of radial artery harvest in the presence
      of an abnormal Allen test.
AB  - BACKGROUND: The Allen test is commonly used to assess collateral hand circulation
      before radial artery harvest for coronary artery bypass grafting. However there
      is no consensus as to whether an abnormal Allen test is an absolute or relative
      contraindication to radial artery harvesting. We assessed the safety of
      harvesting the radial artery using arterial duplex ultrasonography in patients
      with an abnormal Allen test. METHODS: Two hundred and eighty-seven consecutive
      patients scheduled for total arterial coronary revascularisation underwent
      preoperative Allen tests over a 34-month period. Patients with an abnormal Allen
      test underwent duplex ultrasonography preoperatively to assess the adequacy of
      the ulnar collateral supply and the suitability of the radial artery for
      harvesting. RESULTS: Two hundred and forty-four patients (85%) had a normal left
      Allen test and proceeded directly to radial artery harvest. Forty-three patients
      (15%) with an abnormal left Allen test underwent duplex ultrasonography scans and
      of those, 5 patients had an abnormal scan. These patients underwent scanning of
      the contralateral forearm. Three patients had a normal right forearm arterial
      duplex scan and the right radial artery was harvested. The mean diameter of the
      radial and ulnar arteries was not significantly different between the patients
      with normal and abnormal duplex ultrasonograms. There were no ischemic hand
      complications in this series. CONCLUSIONS: The Allen test is a quick, easy, and
      reliable screening test before radial artery harvesting in the majority of
      patients. Duplex ultrasonography predicts safe radial artery harvest in the
      majority of patients with an abnormal Allen test.

PMID- 14726047
TI  - Skeletonization versus pedicle preparation of the radial artery with and without
      the ultrasonic scalpel.
AB  - BACKGROUND: The radial artery (RA) is increasingly used for myocardial
      revascularization because of its presumed advantageous long-term patency rates.
      The vessel can be harvested as a pedicle or skeletonized. The aim of this study
      was to compare the skeletonization technique with pedicle preparation using
      either an ultrasonic scalpel or scissors. METHODS: Forty consecutive patients
      with coronary artery disease undergoing complete arterial revascularization were
      included in the study. In 20 patients the RAs were prepared using scissors and
      clips (group 1: skeletonization; group 2: pedicle). In another 20 patients the
      arteries harvested were prepared using an ultrasonic scalpel (group 3:
      skeletonization; group 4: pedicle). The RA was treated with papaverine to prevent
      spasm of the vessel during and after harvesting. Tissue specimens of each RA were
      taken to analyze endothelial morphology by scanning electron microscopy. After
      implantation of the RA, graft perfusion was measured with a flow probe. RESULTS:
      Harvesting the RA as a skeletonized vessel took more time as compared with
      pedicle preparation (group 1 vs group 2: 37.1 +/- 3.5 minutes vs 24.4 +/- 3.9
      minutes; p < 0.001 and group 3 vs group 4: 31.1 +/- 3.5 minutes vs 25.6 +/- 3.7
      minutes; p < 0.01). The number of hemostatic titanium clips was similarly higher
      in group 1 as opposed to group 2 (58.7 +/- 7.1 vs 38.7 +/- 7.1; p < 0.01).
      However, there was no difference between groups 3 and 4 (p = 0.086). The length
      of the RA after skeletonization with scissors and clips was 20.8 +/- 1.5 cm in
      contrast with 19.1 +/- 0.9 cm (p < 0.01) after dissection as a pedicle. In the
      groups using the ultrasonic scalpel, there was no difference in graft length (p =
      0.062). Mean blood flow through the graft after establishing the proximal
      anastomosis was similar among all groups (groups 1, 2, 3, and 4: 50 +/- 20.1
      mL/min, 53.8 +/- 24.3 mL/min, 56.3 +/- 25.1 mL/min, and 51.8 +/- 23 mL/min,
      respectively). Scanning electron microscopy demonstrated endothelial damage in
      all patients in groups 1, 2, and 3 and in 7 patients of group 4. Most endothelial
      lesions were minor except in group 3 in which 1 of 5 endothelial lesions were
      severe. Statistically significant differences was found between groups 1 and 2,
      and 3 and 4 with respect to the degree of endothelial damage (p < 0.01).
      CONCLUSIONS: Skeletonization using scissors and clips is more time consuming and
      technically more difficult, but yield significantly longer grafts.
      Skeletonization with an ultrasonic scalpel did not result in additional length
      and was more frequently associated with severe endothelial damage. Pedicle
      preparation using scissors or an ultrasonic scalpel is much simpler and faster,
      and does not jeopardize endothelial integrity.

PMID- 14726048
TI  - Nitric oxide and prostacyclin in ultrasonic vasodilatation of the canine internal
      mammary artery.
AB  - BACKGROUND: Investigators recently demonstrated increased free blood flow from
      radial artery free grafts harvested using ultrasonic technology. We investigated
      the mechanism underlying this phenomenon. METHODS: Canine internal mammary artery
      segments (with and without intact endothelium) were precontracted with
      norepinephrine and sonicated 3 seconds in organ chambers with ultrasonic
      coagulating shears (Harmonic Scalpel; Ethicon Endo-Surgery, Cincinnati, OH)
      functioning at level 2. Vessel tension was continuously measured to examine
      vasoactivity in response to sonication alone (control) or with N(u)-Nitro-l
      arginine (l-NNA) and indomethacin added to the chamber medium individually or in
      combination. Tissue heating, acoustic pressure, and endothelial damage as
      detected by scanning electron micrography were also assessed. RESULTS: In vitro
      sonication with the Harmonic Scalpel induced predominately endothelium-dependent
      internal mammary artery vasorelaxation but a small endothelium-independent
      contribution was also observed. Early vasorelaxation (1 minute after stimulus)
      was maximally inhibited by l-NNA alone and in combination with indomethacin.
      Relaxation during this period was insignificantly affected by indomethacin alone.
      Only the combination of l-NNA and indomethacin maximally inhibited late
      vasorelaxation (5 minutes after stimulus), whereas inhibitory effects of l-NNA
      diminished during this time period. Indomethacin inhibited relaxation
      substantially during this phase, although significantly less than did l-NNA
      alone. The Harmonic Scalpel minimally heated the tissue surface (0.3 +/- 0.03
      degrees C) and did not disrupt endothelial cell integrity while operating at 50
      mW/cm(2) intensity (acoustic pressure 40 kPa). CONCLUSIONS: Sonication induces
      vasorelaxation almost completely by time-dependent endothelial nitric oxide and
      prostacyclin release, which appears unrelated to tissue heating or endothelial
      architectural disruption.

PMID- 14726049
TI  - Clinical experience with an implantable, intracardiac, continuous flow
      circulatory support device: physiologic implications and their relationship to
      patient selection.
AB  - BACKGROUND: We have been investigating continuous-flow circulatory support
      devices for 20 years. Unlike pulsatile assist devices, continuous-flow pumps have
      a simplified pumping mechanism and they do not require compliance chambers or
      valves. In the 1980s, clinical experience with the Hemopump proved a high-speed,
      intravascular, continuous-flow pump could safely augment the circulation.
      Subsequently, a decade of animal experiments with a larger, longer-term
      continuous-flow pump (the Jarvik 2000) confirmed the safety and efficacy of
      intraventricular placement, leading to its clinical application. METHODS: We
      analyzed the physiologic and anatomic effect of using the Jarvik 2000 pump for
      cardiac support in 23 patients in whom the device was applied as a bridge to
      transplant under the protocol approved by the Food and Drug Administration
      Investigational Device Exemption. The device was used as a bridge to
      transplantation in 20 patients and as destination therapy in 3 patients. RESULTS:
      In the bridge-to-transplant group, 14 patients underwent transplantation, 5 died
      during the circulatory support period and 1 is in an ongoing study. The support
      period lasted an average of 90 days. For the survivors, the follow-up period has
      averaged 16 months. Within the first 48 postoperative hours, the average cardiac
      index increased by 65% (from 1.77 +/- 0.24 to 2.92 +/- 0.60 L. min(-1). m(-2), p
      = 0.00000002), the systemic vascular resistance decreased by 42% (from 1604 +/-
      427 to 930 +/- 330 dynes/sec per cm(2), p = 0.00001), and the pulmonary capillary
      wedge pressure (PCWP) decreased by 41.8% (from 23 +/- 5.1 to 13.4 +/- 6.6 mm Hg,
      p = 0.00009). Similar results were seen for the patients undergoing destination
      therapy. Cardiac index increased 89.5% (from 1.9 +/- 0.1 to 3.6 +/- 0.6, p =
      0.046) and PCWP decreased by 52.2% (from 23 +/- 10 to 11 +/- 2, p = 0.22). In
      that group, 1 patient died unexpectedly from an accident 382 days after device
      implantation. The 2 survivors remain in New York Heart Association (NYHA)
      functional class I at 700 to 952 days after implantation. CONCLUSIONS: The Jarvik
      2000 can offer effective long-term support for patients with chronic heart
      failure and NYHA class IV status. However, the new physiology produced by
      continuous offloading of the heart throughout the cardiac cycle has introduced
      unique clinical problems. The understanding of the problems generated by this
      biotechnological interface is essential for obtaining optimal clinical outcomes.

PMID- 14726050
TI  - Left ventricular pressure and volume unloading during pulsatile versus
      nonpulsatile left ventricular assist device support.
AB  - BACKGROUND: Nonpulsatile axial or centrifugal pumps are the latest generation of
      left ventricular assist devices (LVAD). Whether left ventricular (LV) unloading
      and outcome in these devices is similar to pulsatile LVADs during long-term
      support has not been investigated. We compared LV unloading and mortality between
      different types of LVAD support (pulsatile versus nonpulsatile). METHODS: In 31
      patients undergoing long-term LVAD implantation (nonpulsatile = 10, pulsatile =
      21) preoperative and postoperative echocardiographic and hemodynamic assessment
      with right heart catheterization had been obtained. RESULTS: All patients had
      similar echocardiographic, hemodynamic, and clinical heart failure
      characteristics at baseline. The degree of LV pressure unloading was the same in
      both device types, caused by similar reduction of mean pulmonary pressure (18.6
      +/- 5.1 versus 18.3 +/- 7.5 mm Hg) and pulmonary capillary wedge pressure (8.9 +/
      4.4 versus 8.0 +/- 7.0 mm Hg). Left ventricular volume unloading was pronounced
      with a pulsatile device owing to a statistically significant higher pump output
      (5.1 +/- 1.0 L/min) in comparison with nonpulsatile LVADs (3.6 +/- 0.9 L/min, p <
      0.001). Echocardiographic-determined end-systolic indicators confirm this
      augmentation in pulsatile LVADs. Etiology or the time interval of hemodynamic
      reassessment had no impact in left ventricular pressure unloading, but LV volume
      unloading decreased between day 60 and 120 in patients with nonpulsatile LVADs.
      The preoperative and postoperative transplant mortality was comparable in both
      groups. CONCLUSIONS: Left ventricular pressure unloading is similar in patients
      with nonpulsatile as compared with pulsatile implantable long-term assist
      devices. Left ventricular volume unloading is pronounced in pulsatile LVADs.

PMID- 14726052
TI  - Five-year results of 219 consecutive patients treated with extracorporeal
      membrane oxygenation for refractory postoperative cardiogenic shock.
AB  - BACKGROUND: Postcardiotomy cardiogenic shock occurs in approximately 1% of
      patients. We prospectively evaluated the early and long-term outcome as well as
      predictors of survival when using temporary extracorporeal membrane oxygenation
      (ECMO) support. METHODS: During 5 years 219 of 18150 patients (1.2%) undergoing
      cardiac surgery (coronary artery bypass grafting, n = 119; aortic valve
      replacement, n = 24; coronary artery bypass grafting and aortic valve
      replacement, n = 21; coronary artery bypass grafting and mitral valve
      replacement, n = 11; other procedures, n = 44) required temporary postoperative
      ECMO support. The ECMO implantation was performed through the femoral vessels or
      through the right atrium and ascending aorta. Additional intraaortic balloon
      counterpulsation was employed in 144 patients to improve coronary blood flow.
      RESULTS: Mean duration of ECMO support was 2.8 +/- 2.2 days. One hundred thirty
      four patients (60%) were successfully weaned from ECMO. Of these, 52 patients
      (24%) were discharged from the hospital after 29.9 +/- 24 days. The main cause of
      death was myocardial failure. Five-year follow-up is 96% complete; 37 patients
      (74%) were alive with reasonable exercise capacity. CONCLUSIONS: Extracorporeal
      membrane oxygenation is an acceptable technique for short-term treatment of
      refractory postoperative low cardiac output. It can save the lives of a group of
      very high risk patients.

PMID- 14726054
TI  - Hemodynamic unloading of the failing left ventricle using an arterial-to-arterial
      extracorporeal flow circuit.
AB  - We tested the hypothesis that creation of a constant-flow extracorporeal circuit
      between the proximal and distal aorta will unload the failing left ventricle.
      Studies were performed in 14 heart failure dogs produced by intracoronary
      microembolizations. An extracorporeal circuit incorporating a diagonal pump was
      placed between a femoral and a carotid artery, with flow directed to the carotid.
      Hemodynamic measurements were made with the pump delivering 0.25 L/min through
      the circuit for 4 hours (active group). Measurements obtained from 8 sham
      operated heart failure dogs were used for comparison (control group). Heart rate,
      peak left ventricular systolic pressure, left ventricular end-diastolic pressure,
      end-diastolic volume, end-systolic volume, and ejection fraction were measured at
      baseline and at 30, 60, 120, and 240 minutes. There were no differences in any of
      the hemodynamic values during the 4 hours of follow-up in the control group. In
      the active group, there was no effect on heart rate or peak systolic pressure,
      but reductions between baseline and 240 minutes were observed in left ventricular
      end-diastolic pressure (15 +/- 1 vs 6 +/- 1 mm Hg, p < 0.05), end-diastolic
      volume (61 +/- 3 vs 50 +/- 3 mL, p < 0.05), and end-systolic volume (44 +/- 2 vs
      32 +/- 2 mL, p < 0.05), and an increase in ejection fraction (28 +/- 2 vs 37% +/-
      2%, p < 0.05). Acute use of this artery-to-artery extracorporeal system
      effectively unloads the failing left ventricle. The potential benefits of this
      approach on long-term myocardial recovery in heart failure require further
      investigation.

PMID- 14726055
TI  - Plasma brain natriuretic peptide reflects left ventricular function during
      percutaneous cardiopulmonary support.
AB  - BACKGROUND: Plasma levels of brain natriuretic peptide (BNP), a cardiac hormone
      secreted predominantly from the ventricle, are elevated in patients with
      myocardial infarction, hypertension, and dilated cardiomyopathy. In this study,
      we assessed the usefulness of measuring BNP to evaluate left ventricular function
      in patients with severe heart failure receiving mechanical circulatory support.
      METHODS: Plasma BNP and creatine kinase (CK)-MB levels were measured serially in
      8 consecutive patients with cardiogenic shock who received percutaneous
      cardiopulmonary support (PCPS) at Osaka Police Hospital from August 1999 to March
      2000. Coronary artery bypass grafting or percutaneous transluminal coronary
      angioplasty was also performed in 5 patients during PCPS; in addition, 1 patient
      underwent insertion of a left ventricular venting catheter and implantation of a
      left ventricular assist system after PCPS. RESULTS: Five patients were weaned
      from PCPS, and 3 died. In survivors, plasma BNP and CK-MB levels correlated
      positively and significantly (r = 0.968, p = 0.03). After PCPS was initiated,
      plasma BNP levels gradually decreased in survivors, but not in patients who died
      (p = 0.003). CONCLUSIONS: These results suggest that plasma BNP levels accurately
      reflect myocardial damage in patients undergoing PCPS. A decrease in BNP might
      appear to indicate improved left ventricular function and predict successful
      weaning from mechanical support.

PMID- 14726057
TI  - Surgery for aortic root aneurysm in children: a 21-year experience in 50
      patients.
AB  - BACKGROUND: Ascending aortic aneurysms are unusual in children and have received
      little attention to develop guidelines for management. This study reviewed our
      experience with 50 children who have undergone aortic root replacement for
      ascending aortic aneurysm. METHODS: A retrospective clinical review was conducted
      using hospital charts and office records. Patients or their physicians were
      contacted for follow-up and recent echocardiograms were obtained and reviewed.
      RESULTS: There was no operative or hospital mortality. Twenty-six children had
      aortic root replacement with a composite graft, 10 patients had replacement with
      a homograft aortic root, and 14 patients had a David II valve-sparing procedure.
      Factors related to late morbidity and mortality were analyzed. Long-term results
      were excellent in the 26 children receiving a composite graft. Twenty-three of
      these children were New York Heart Association class I (19) or II (4) at study
      closure. There were 3 late deaths (11, 16, and 17 years postoperative). Seven of
      10 children receiving a homograft aortic root are long-term survivors and all 14
      children having a valve-sparing procedure are alive. Generally, late results with
      the David II remodeling procedure have been good although 3 patients developed
      late aortic insufficiency and two required valve replacement. CONCLUSIONS: Aortic
      root replacement in children with aneurysms has low operative risk and good long
      term results. Composite grafts in particular carry a low risk of endocarditis,
      thromboembolism, and hemorrhagic events. Homografts are suitable for small
      patients but lack durability. Late results with the David II remodeling valve
      sparing procedure in children have been compromised by late root dilatation.

PMID- 14726058
TI  - The congenitally bicuspid aortic valve: how does it function? Why does it fail?
AB  - BACKGROUND: The study was intended to investigate the reason why congenitally
      bicuspid valves (CBAVs), which may function hemodynamically and clinically well,
      have a high early failure rate. METHODS: Observations were made on cryopreserved,
      then thawed human aortic roots containing CBAVs. Valvular function was studied in
      the left heart simulator using conventional and 500-frames/second cinematography,
      intravascular ultrasound, by preparation of silicone molds, and by computerized
      digital modeling. RESULTS: The function of the clinically "normal" CBAVs is
      characterized by (a). excessive folding and creasing, which (unlike in the
      trileaflet valve) persist throughout the cardiac cycle; (b). extended areas of
      leaflet contact; (c). significant morphologic stenosis; and (d). asymmetrical
      flow patterns and turbulence. CONCLUSIONS: The above features subject the CBAV to
      abnormally high stresses and may lead to early thickening and eventually
      calcification and stenosis. The abnormal flow patterns also predilect for
      dilatation and dissection of the ascending aorta.

PMID- 14726059
TI  - Viability and histologic structure of porcine valves after cryopreservation.
AB  - BACKGROUND: Increased awareness of the limitations of current cardiac valve
      substitutes has generated a renewed interest in the use of allograft valves. The
      effects of currently used preservation techniques on the viability of the valve
      leaflets and the longevity of the implantation however remain controversial. The
      objective of this study is to analyze the influence of ischemic time,
      sterilization methods with or without fungicides, and storage procedures on the
      viability of the valve leaflets and on the histologic structure of the arterial
      wall, valve leaflet, and myocardium. METHODS: The tissue sources were hearts from
      40 pigs with 1 hour of warm ischemic time. The aortic and pulmonary valves were
      dissected after 2 or 24 hours of cold ischemic time. They were stored in
      antibiotic solution for 20 hours at 4 degrees C with or without an antifungal
      agent. The samples were cryopreserved using a programmed temperature decrease
      method. After 1 week of storage in a liquid nitrogen tank, either in a gas or a
      liquid phase, the cardiac valves were slowly thawed and examined. RESULTS:
      Pulmonary valves showed greater viability than aortic valves. Decreased cellular
      viability was observed independent of cold ischemic time, treatment with
      amphotericin B, or the storage method used. Treatment with or without
      amphotericin B had no influence on cellular viability. Conversely it was observed
      that there was greater cellular viability among those valves stored in a liquid
      phase. As far as the histologic structure of the valve is concerned we did not
      observe any influence either in the treatment with amphotericin B or the storage
      method used although it was observed that reduction of the cold ischemic time
      minimized histologic injury. CONCLUSIONS: Optimization of preservation methods
      may decrease the negative effects of cryopreservation on cell viability and
      histologic structure of the valve.

PMID- 14726060
TI  - Hemolysis after mitral valve repair: mechanisms and treatment.
AB  - BACKGROUND: The objectives of this study were to determine the mechanisms of
      hemolysis after mitral valve repair and to determine outcomes after surgical
      treatment (mitral replacement or re-repair). METHODS: Between 1981 and 2002, 32
      patients (mean age, 58 years) presented with hemolytic anemia after mitral valve
      repair for degenerative, rheumatic, or ischemic mitral regurgitation (MR). Three
      types of annuloplasty were used at the initial mitral valve repair: Cosgrove
      Edwards, Carpentier-Edwards, and bovine pericardial (Perigard). The diagnosis and
      the mechanisms of hemolysis were investigated with laboratory testing and
      echocardiography. RESULTS: Median interval from initial mitral valve surgery to
      diagnosis of hemolysis was 3 months (range, 1 week to 4 years). At presentation,
      mean hematocrit was 27.5% +/- 4.9% and 22 patients (69%) required transfusion.
      Echocardiographic findings varied. Twenty-four patients (77%) had grade 3 or 4
      MR. Mitral regurgitant jet types included fragmentation (11 patients, 34%),
      acceleration (10, 31%), slow deceleration (5, 16%), collision (4, 13%), and free
      jet (2, 6%). Mitral valve replacement was performed in 28 patients, mitral valve
      re-repair in 3, and 1 patient did not undergo reoperation. At reoperation the
      mitral valve repair was physically intact in 25 of 31 patients (81%). There were
      2 hospital deaths in patients having reoperation (6%). Actuarial survival was 95%
      at 1 year and 85% at 5 years. In 1 patient recurrent mechanical hemolysis
      developed caused by a perivalvular leak after mitral valve replacement.
      CONCLUSIONS: Hemolysis is a mode of failure of mitral valve repair. Patients with
      hemolysis generally present within 3 months of mitral valve repair. Although
      echocardiographic features varied, most patients had high-grade MR and
      regurgitant jets that fragmented or accelerated. Mitral valve replacement yields
      favorable outcomes for patients with hemolysis after mitral valve repair.

PMID- 14726061
TI  - Preclinical assessment of a trileaflet mechanical valve in the mitral position in
      a calf model.
AB  - BACKGROUND: The bileaflet valve is currently the mechanical replacement valve of
      choice. Though durable, it does not closely mimic native valve hemodynamics and
      remains potentially thrombogenic. METHODS: Prototype trileaflet valves (T1 and
      T2) were implanted in the mitral position in calves. Group I calves received
      either a T1 valve (n = 12) or a control bileaflet valve (n = 5); Group II, either
      a T2 valve (n = 7) or a control bileaflet valve (n = 5). Valve function,
      perivalvular leakage, and transvalvular pressure gradients were evaluated. Also,
      long-term prototype leaflet wear was evaluated in vivo in one Group I calf (502
      days) and two Group II calves (385 and 366 days). Calves were euthanized and
      necropsied at study termination, and major organs weighed and examined. RESULTS:
      Valve function was excellent and hematologic parameters remained normal in all
      calves that survived to study termination. Mean peak transvalvular pressure
      gradients were 10 +/- 7 mm Hg for T1 valves, 6 +/- 3 mm Hg for T2 valves, and 12
      +/- 4 mm Hg for bileaflet control valves. Clinically insignificant valvular
      regurgitation was observed in both prototypes. Explanted valves showed no
      thrombus-impaired leaflet motion, except in two T1-fitted calves and one T2
      fitted calf. Major organs showed no evidence of clinically significant
      thromboembolic events. There were no other significant differences between the
      results of experimental and control groups. CONCLUSIONS: Prototype trileaflet
      valves performed safely and effectively in the mitral position in calves, even
      without long-term anticoagulation. This warrants their evaluation as an
      equivalent alternative to bileaflet valves.

PMID- 14726062
TI  - Biomechanical comparison of median sternotomy closures.
AB  - BACKGROUND: Poor healing of median sternotomy can significantly increase
      morbidity, mortality, and hospital costs. Effective union requires reliable
      sternal fixation. Although wire has proven the most reliable and widely used
      sternotomy closure material, no experimental studies have compared a large
      variety of wiring techniques in a human model. We developed an easily
      reproducible experimental model using cadaveric human sterna and compared several
      wiring methods to assess closure strength and stability. METHODS: Fifty-three
      fresh adult human cadaveric sternal plates with adjacent ribs were fixed with
      specially designed spiked stainless steel clamps and attached to a texture
      analyzer. Single peristernal and transsternal, alternating single peristernal and
      transsternal, figure-eight peristernal, figure-eight pericostal, and Robicsek
      closures using no. 5 stainless steel wires were tested. We evaluated bone
      density, stiffness, and displacement using perpendicular, repetitive variable
      force loads of 800 Newtons cycling at a rate of 0.5 mm/s. RESULTS: There were no
      significant differences in age, sex, or bone density in outcome measures of the
      sternal groups. No clamp failures or clamp damage to the specimens occurred. The
      single peristernal and alternating peristernal and transsternal closures proved
      superior in strength and stability (p < 0.001). The figure-eight peristernal,
      then the single transsternal, then the Robicsek were next stablest groups in
      decreasing order. The figure-eight pericostal closure had the highest failure
      rate (p < 0.001). CONCLUSIONS: This novel model of sternotomy closure testing was
      reliable, inexpensive, and easily reproducible. The mechanical stability of
      peristernal and alternating peristernal and transsternal wires was significantly
      greater than that of the other tested methods. Pericostal figure-eight closures
      were not sufficiently stable to be considered a reliable method of primary
      sternotomy repair.

PMID- 14726063
TI  - A modified parasternal wire technique for prevention and treatment of sternal
      dehiscence.
AB  - BACKGROUND: Sternal dehiscence with or without mediastinitis is a devastating
      complication of median sternotomy. Various techniques of sternotomy closure
      including 'figure of eight' wire sutures, nylon bands, and custom-made titanium-H
      plates have been described. We have devised and tested a new method of sternal
      closure to prevent sternal wound complications in patients at high risk of
      sternal dehiscence. METHODS: 1336 patients underwent sternotomy for various
      cardiac operations from January 1996 to January 2002. Patients were divided into
      two groups. Group I consisted of 560 patients who did not have any high risk
      factors for sternal dehiscence and received a standard six wire closure. Group II
      comprised of patients at high risk of sternal dehiscence and were divided
      randomly into subgroup II A (n = 390), which included patients who had
      conventional sternal closure. While in subgroup II B (n = 386) patients had a
      modified parasternal wire closure according to the finalized protocol. RESULTS:
      Sternal instability was noticed in 1/560 and none had sternal dehiscence in group
      I, but 16/390 patients had sternal instability and 3/390 had sternal dehiscence
      in subgroup II A, whereas only one patient in high risk subgroup II B developed
      sternal dehiscence with mediastinitis and required a pectoral flap advancement
      for sternal closure. CONCLUSIONS: Use of modified parasternal wire closure in
      patients with a high risk of sternal dehiscence is a safe, effective, technically
      easily reproducible, as well as economical, method of preventing and treating
      sternal dehiscence.

PMID- 14726064
TI  - Markers for endothelial activation during open heart surgery.
AB  - BACKGROUND: Reliable markers for endothelial activation are needed when studying
      biocompatibility of cardiopulmonary bypass. METHODS: Blood samples from 21
      patients undergoing combined valve and coronary artery bypass surgery were
      collected before anesthesia (T1), after re-transfusion of blood from the heart
      lung machine (T2), and on the first postoperative morning (T3). Concentrations of
      soluble markers were determined using sandwich enzyme-linked immunoadsorbent
      assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also used to stimulate
      human umbilical vein endothelial cells (HUVEC) in culture for 6 hours, in which
      activation was measured using cell enzyme immunoassay for mICAM-1 and mVCAM-1.
      RESULTS: The concentrations of sICAM-1 and sVCAM-1 increased during both
      measurement intervals (p < 0.05). The sICAM-1 T1 was 311.0 ng/mL (range, 271.0 to
      350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range, 322.0 to 422.0 ng/mL), and
      the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4 ng/mL; the sVCAM-1 T1 was
      607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1 T2 was 755.3 ng/mL (range,
      660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0 ng/mL (946.0 to 1406.0
      ng/mL); whereas the sE-selectin increased from T1 to T3 (p < 0.01). Both the
      mICAM-1 (p < 0.002) and the mVCAM-1 (p < 0.005) increased on the human umbilical
      vein endothelial cells in culture after stimulation with the patient sera. The
      amounts of soluble markers in vivo were not correlated with the degree of
      endothelial activation in vitro, but were correlated with various operative
      variables including age, medication, and time of aortic cross-clamping.
      CONCLUSIONS: Endothelial cells were activated during cardiopulmonary bypass. The
      soluble adhesion molecules sICAM-1, sVCAM-1, and sE-selectin displayed different
      kinetics, rendering it difficult to determine a simple expression for the degree
      of endothelial cell activation. Clinically, sVCAM-1 seemed to be the best-suited
      marker for endothelial cell activation, because it was only associated with
      aortic cross-clamping and heparin and protamine doses, and it also showed the
      largest numerical changes.

PMID- 14726065
TI  - Sonoclot analysis in cardiac surgery in dialysis-dependent patients.
AB  - BACKGROUND: Dialysis-dependent patients have multiple disorders of hemostasis;
      however, there are no reports of viscoelastic changes during cardiac surgery in
      such patients. METHODS: Hemostasis in dialysis-dependent patients during cardiac
      operations was evaluated. Thirty patients who underwent cardiopulmonary bypass
      (CPB) were studied: 6 with chronic renal failure undergoing dialysis (HD group),
      and 24 without hemodialysis. Blood samples were obtained at four points: before
      sternotomy, 30 and 90 minutes after the start of CPB, and after protamine
      administration. RESULTS: Activated clotting time (ACT) measured with Sonoclot
      analyzer was significantly correlated with ACT measured traditionally (r = 0.92;
      p < 0.001; y = 36.1 + 0.95x). Values for ACT measured with Sonoclot analyzer as
      well as traditional ACT increased significantly during CPB. Values for ACT
      measured with Sonoclot analyzer in the HD group were significantly longer than
      those in the control group. Before CPB, both ACT measured with Sonoclot analyzer
      and traditional ACT in the HD group were significantly longer than those in the
      control group; however, there were no significant differences in ACT measured
      with Sonoclot analyzer between the groups after CPB. Clot rates and peak signal
      values were significantly decreased during CPB in both groups, and returned to
      preoperative values after protamine administration. There were no significant
      differences in clot rate and peak signal values between the two groups. There
      were no differences between the two groups in changes of time to peak. Platelet
      counts in the HD group were significantly higher (p < 0.05) than those in the
      control group. There were no differences in platelet counts after CPB between the
      two groups. Antithrombin III levels decreased below 50% during and after CPB.
      Antithrombin III in the HD group was significantly lower (p < 0.01) than those in
      the control group. A significant time-group interaction was observed in
      antithrombin III levels. CONCLUSIONS: Sonoclot signatures in HD patients showed
      no significant differences in viscoelastic changes compared with non-HD patients.

PMID- 14726066
TI  - Diazoxide provides protection to human myocardium in vitro that is concentration
      dependent.
AB  - BACKGROUND: Diazoxide has been shown to confer significant myocardial protection
      in many experiments. This study was designed to assess its influence on the
      structural injury and functional recovery of human myocardium subjected to
      hypoxia/reoxygenation in vitro. METHODS: The isolated electrically driven human
      right atrial trabeculae, obtained during cardiac surgery, were studied. The
      tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being
      obtained by replacing oxygen with argon. The influence of diazoxide on atrial
      contractility was studied first. Next, the two trabeculae from one atrial
      appendage were studied simultaneously, adding diazoxide to the tissue bath 10
      minutes before hypoxia in one, with another serving as a control. We tested 10(
      4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30,
      60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60
      minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(
      4) mol/L norepinephrine. Apart from continuous recording of the contraction
      force, we measured the troponin I release into the tissue bath after ischemia and
      reoxygenation. RESULTS: Diazoxide exerted a negative inotropic effect in human
      atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied
      resulted in better functional recovery of atrial trabeculae subjected to 30
      minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration
      provided significant protection as assessed by contractility. After 120 minutes
      of reoxygenation, only diazoxide-treated muscle was viable enough to respond to
      norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release
      during hypoxia and reoxygenation. CONCLUSIONS: This study shows that diazoxide
      provides significant concentration-dependent protection against
      hypoxia/reoxygenation injury to human myocardium in vitro.

PMID- 14726067
TI  - Atrial natriuretic peptide protects against ischemia-reperfusion injury in the
      isolated rat heart.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP), a stimulator of particulate
      guanylate cyclase, has been found to protect against reoxygenation-induced
      hypercontracture in isolated cardiomyocytes by increasing cyclic guanosine
      monophosphate synthesis. The purpose of this study was to investigate the
      cardioprotective effects of ANP against ischemia-reperfusion injury in isolated
      rat hearts. METHODS: Twenty-four hearts were perfused with ANP at 0.01, 0.1, and
      1 micromol/L or without ANP (n = 6 each) in normoxic conditions. Because 0.1
      micromol/L ANP induced a threefold increase in cyclic guanosine monophosphate
      release into the coronary effluent without any effect on cardiac function, we
      used the 0.1 micromol/L ANP dose for ischemia-reperfusion studies. Eighteen
      hearts were subjected to 15 minutes of normothermic global ischemia followed by
      15 minutes of reperfusion. The hearts were divided into three groups (n = 6
      each). RESULTS: In group 1, ANP was added before ischemia. In group 2, ANP was
      added to the reperfusate. Hearts were untreated in the control group. In group 1,
      the postischemic recovery of cardiac output, coronary flow, and cyclic guanosine
      monophosphate release was similar to the control group. In group 2, the recovery
      of cardiac output was significantly better than the control group (82.1% +/- 9.8%
      vs 61.8% +/- 6.8%, respectively, p < 0.01) with a similar trend to recovery of
      coronary flow (90.7% +/- 8.5% vs 79.3% +/- 11.8%, respectively). The improved
      cardiac function was closely related to a significant increase in postischemic
      cyclic guanosine monophosphate release. CONCLUSIONS: Administration of ANP at the
      time of reperfusion protects the myocardium from ischemia-reperfusion injury. The
      concentrations of administration must not only increase the release of cyclic
      guanosine monophosphate release, but also lack negative inotropic effects.

PMID- 14726068
TI  - Effects of sildenafil analogue UK 343-664 on a porcine model of acute pulmonary
      hypertension.
AB  - BACKGROUND: Sildenafil (Pfizer Pharmaceuticals, Sandwich, Kent, UK) has been
      associated with pulmonary vasorelaxation. A more potent Sildenafil analogue (UK
      343-664 [Pfizer Pharmaceuticals]) has been developed, but its effects in vivo
      have not been studied. This study evaluated the effects of UK 343-664 (Pfizer)
      during acute pulmonary hypertension. METHODS: Fourteen adult swine were
      anesthetized with 1 minimum alveolar concentration isoflurane and were
      mechanically ventilated with an FIO(2) of 50%. End tidal CO(2) was maintained
      between 32 and 36 mm Hg. Micromanometer tipped catheters were placed in the
      ascending aorta, pulmonary artery, and right ventricle. Pulmonary flow was
      measured with a perivascular probe using transit time ultrasound. RESULTS:
      Pulmonary hypertension was induced with a continuous infusion of the thromboxane
      analogue U46619. Animals were randomized into two groups. Group 1 (n = 9)
      received 500 microg of UK 343-664 (Pfizer) intravenously for more than 2 minutes.
      Group 2 (n = 5) served as the control group. Data were recorded continuously for
      60 minutes. Statistical analyses were performed with the analysis of variance and
      t tests. A p less than 0.05 was considered significant.Pulmonary hypertension was
      achieved in all animals. The administration of UK 343-664 (Pfizer) was associated
      with a significant decrease in pulmonary artery pressure (30.3%; p < 0.05) and
      pulmonary vascular resistance (42%; p < 0.05) with mild systemic vasodilatation.
      These effects were partially maintained at 30 minutes (a 17.3% and 39% decrease,
      respectively; p < 0.05). CONCLUSIONS: The administration of UK 343-664 (Pfizer)
      was associated with predominant pulmonary vasodilatation without systemic
      hypotension. This may represent a significant advance in the treatment of acute
      pulmonary hypertension. Potential clinical implications for this new
      phosphodiesterase enzyme type V (PDEV) inhibitor merit further study.

PMID- 14726069
TI  - An experimental study of surgical ultrasonic angioplasty: its effect on
      atherosclerosis and normal arteries.
AB  - BACKGROUND: We have developed a new hand-held probe for surgically open
      ultrasonic angioplasty. Two experimental studies were conducted to determine the
      optimal power range for carrying out ultrasonic angioplasty. METHODS: The probe
      measured 2.5 mm in diameter and 5 cm in length. The amplitude was 210 microm at
      100% power. One of the studies was designed to determine the power range that is
      effective for removal of atherosclerotic lesions. Human cadaveric arteries were
      used in the study. The other study was designed to investigate the long-term
      adverse effect on normal arteries. Canine arteries were used in this study.
      RESULTS: In the study using cadaveric arteries, the amplitude ranging from 90 to
      110 microm was effective for soft atheroma, the range from 110 to 130 microm was
      effective for mild arteriosclerosis, and 150 microm was effective for calcified
      lesions. The other study of the long-term effect on canine normal arteries
      indicated that each incidence of stenosis and occlusion was 0% at amplitude
      ranging from 90 to 110 microm, 13% at 130 microm, and 25% at 150 microm.
      CONCLUSIONS: The surgically open ultrasonic angioplasty with a new hand-held
      probe was effective for various kinds of atherosclerotic lesions, whereas the
      angioplasty at high amplitude had a problem with the long-term effect on normal
      arteries.

PMID- 14726070
TI  - The prognostic role of c-kit protein expression in resected large cell
      neuroendocrine carcinoma of the lung.
AB  - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade
      neuroendocrine tumor of the lung that shares some clinicopathologic and molecular
      features with small cell lung carcinoma (SCLC). Optimal treatment has not yet
      been standardized and significant prognostic factors are lacking. Because c-kit
      protein overexpression has been recently reported as a negative prognostic factor
      in SCLC we investigated its expression and prognostic value in a series of LCNEC.
      METHODS: Resected LCNEC fulfilling the morphologic criteria of the 1999 World
      Health Organization classification of lung tumors and showing neuroendocrine
      differentiation by appropriate immunohistochemical markers were retrospectively
      reviewed. Immunostaining for c-kit protein expression was performed using the
      polyclonal antibody CD117. Clinical and pathologic characteristic were reported
      and analyzed and a survival study was performed. RESULTS: Thirty-three patients
      underwent radical resection. Thirty-one were male (94%) and 32 were smokers
      (97%). Ten (30.3%), 11 (33.3%), 5 (15.2%), and 7 (21.2%) were at stage IA, IB,
      IIB, and IIIA respectively. Overall 1-, 3-, and 5-year survival rates were
      respectively 79%, 58%, and 51%. Survival analysis showed no differences for any
      of the clinicopathological features except for CD117 immunostaining: 1-year and 3
      year survival rates were respectively 91% and 82% for CD117-negative LCNEC, and
      72% and 44% for CD117-positive ones (p = 0.046). Positivity of CD117 was
      significantly related to recurrence rate: 60% versus 23% for CD117 positive and
      negative LCNEC respectively (p = 0.037). CONCLUSIONS: Radical resection of large
      cell neuroendocrine carcinoma achieves poor outcomes. The c-kit protein is
      frequently expressed in this neoplasia and its expression represents a negative
      prognostic factor. This immunohistochemical marker may represent the basic
      rationale to select LCNEC for novel targeted therapy.

PMID- 14726072
TI  - Positron emission tomography scanning poorly predicts response to preoperative
      chemotherapy in non-small cell lung cancer.
AB  - BACKGROUND: The ability to accurately predict pathologic response to preoperative
      chemotherapy may have a significant impact on the treatment strategy for non
      small cell lung cancer (NSCLC). The purpose of this study was to examine the
      accuracy of positron emission tomography (PET) scanning in predicting the
      pathologic response to preoperative chemotherapy in the primary tumor and
      draining lymph nodes. METHODS: A total of 25 patients were enrolled in two
      separate phase II trials investigating induction chemotherapy for NSCLC. All
      patients underwent pre-treatment and post-treatment PET scans followed by
      surgical resection. A significant PET scan response was defined as a reduction in
      the standard uptake value by 50% or more. We defined a major pathologic response
      as either no disease or microscopic disease only in the primary tumor. The
      percentage change in standard uptake value was then calculated and correlated
      with pathologic response in the primary tumor. In addition, the presence or
      absence of nodal metastases as determined by the postchemotherapy PET scan was
      compared with final pathologic nodal stage. RESULTS: The positive and negative
      predictive values for PET detection of major pathologic response in the primary
      tumor were 43% and 100%, respectively. Positron emission tomography did not
      accurately predict nodal status in 52% of patients. The positive and negative
      predictive values of PET to detect node-positive disease were 73% and 64%,
      respectively. For N2 disease the positive predictive value of PET scans was less
      than 20%. CONCLUSIONS: Positron emission tomography scanning does not reliably
      predict pathologic response to preoperative chemotherapy in NSCLC in either the
      primary tumor or the draining lymph nodes.

PMID- 14726074
TI  - Respiratory function changes after chemotherapy: an additional risk for
      postoperative respiratory complications?
AB  - BACKGROUND: Patients receiving chemotherapy for lung cancer usually modify their
      lung function during treatment with increases in forced expiratory volume in 1
      second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion
      for carbon monoxide (DLCO). This prospective study was designed to evaluate
      functional changes in forced expiratory volume in 1 second, forced vital
      capacity, and DLCO after three courses of induction chemotherapy with cisplatinum
      and gemcitabine in stage IIIa lung cancer patients and to assess their impact on
      respiratory complications after lung resection. METHODS: From March 1998 to
      January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had
      surgical resection after neoadjuvant treatment. Pre-chemotherapy and
      postchemotherapy results of standard respiratory function tests and DLCO were
      compared in patients with and without postoperative respiratory complications.
      RESULTS: All 30 patients completed the chemotherapy protocol without respiratory
      complications. Significant improvements (p < 0.05) were recorded after
      chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm
      Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced
      vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was
      significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as
      well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One
      patient died after surgery and 4 patients (13.3%) experienced postoperative
      respiratory complications. Compared with patients without complications, these 4
      patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%;
      p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03).
      Impact of change in DLCO on postoperative respiratory complications was not
      confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS: In
      lung cancer patients, forced expiratory volume in 1 second and forced vital
      capacity assessed after neoadjuvant chemotherapy are not reliable indicators of
      the likelihood of respiratory complications after surgery. The risk of
      respiratory complication may be directly linked to loss of DLCO/Va. Lung
      diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably
      the most sensitive risk indicator of respiratory complications after surgery. We
      recommend that DLCO studies be performed before and after chemotherapy in lung
      cancer patients undergoing induction therapy.

PMID- 14726076
TI  - Stair climbing test as a predictor of cardiopulmonary complications after
      pulmonary lobectomy in the elderly.
AB  - BACKGROUND: The objective of this study was to assess the role of a symptom
      limited stair climbing test in predicting postoperative cardiopulmonary
      complications in elderly candidates for lung resection. METHODS: A consecutive
      series of 109 patients more than 70 years of age who underwent pulmonary
      lobectomy for lung carcinoma from January 2000 through May 2003 formed the
      prospective database of this study. All patients in the analysis performed a
      preoperative symptom-limited stair climbing test. Univariate and multivariate
      analyses were performed to identify predictors of postoperative cardiopulmonary
      complications. RESULTS: At univariate analysis, the patients with complications
      had a lower forced expiratory capacity percentage of predicted (p = 0.048),
      predicted postoperative forced expiratory volume in 1 second percentage of
      predicted (p = 0.049), climbed a lower height at preoperative stair climbing test
      (p = 0.0004), and presented a greater proportion of cardiac comorbiditiy with
      respect to the patients without complications (p = 0.02). After logistic
      regression analysis, significant predictors of postoperative complications
      resulted in the presence of a concomitant cardiac disease (p = 0.04) and a low
      height climbed preoperatively (p = 0.0015). CONCLUSIONS: A symptom-limited stair
      climbing test was a safe and simple instrument capable of predicting
      cardiopulmonary complications in the elderly after lung resection.

PMID- 14726077
TI  - Pulmonary resection in octogenarians with stage I nonsmall cell lung cancer: a 22
      year experience.
AB  - BACKGROUND: Recent reports indicate that age is not a contraindication to
      pulmonary resection for octogenarians with nonsmall cell lung cancer (NSCLC), but
      other data are lacking. The purpose of this study was to determine outcomes in
      these patients, particularly short- and long-term survival with stage I disease.
      METHODS: A retrospective cohort of 68 octogenarians with NSCLC who underwent
      curative resection from 1980 to 2002 was followed-up for outcomes. RESULTS:
      Median age was 82 years old (range, 80-87 years old) consisting of 44 males
      (65%), with a mean follow-up of 32 months (range, 1-178 months). Operations
      included: 47 lobectomies (69%), 11 wedge resections (16%), 5 segmentectomies
      (8%), 4 bilobectomies (6%), and 1 pneumonectomy (1%). There were 31
      adenocarcinomas (46%), 18 squamous carcinomas (26%), 12 bronchioalveolar
      carcinomas (18%), 4 large cell carcinomas (6%), and 3 miscellaneous malignant
      neoplasms (4%). Median hospital stay was 7 days (range, 3-53 days). Thirty-day
      mortality was 8.8% (n = 6) with 83% developing cardiopulmonary complications.
      Overall actuarial survival at 1, 3, and 5 years was 73%, 51%, and 34%,
      respectively. Of 41 patients (60%) with stage I disease, 23 were T1 lesions. Five
      year survival was significantly different between stages Ia and Ib patients (61%
      and 10%, respectively, p = 0.001). Patients in more advanced stages had a 5-year
      survival of 3/27 (11%). Multivariate analysis identified advanced tumor stage,
      lower ASA physical status, and low FEV(1) as factors associated with poorer long
      term survival. CONCLUSIONS: The 5-year survival, particularly in patients with
      stage Ia tumors with favorable ASA and FEV(1), supports the notion that health
      status and tumor stage outweigh chronologic age in determining surgical
      candidates.

PMID- 14726078
TI  - Selective lobar collapse for video-assisted thoracic surgery.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) is conventionally performed
      under single-lung ventilation. A small proportion of patients are often excluded
      from undergoing VATS because of their inability to tolerate single-lung
      ventilation. We describe a simple technique of selective lobar lung collapse that
      may help to recruit additional, selected patients for VATS. METHODS: We use a
      standard suction catheter placed under bronchoscopic guidance to the target lobar
      bronchus through a single-lumen endotracheal tube. The catheter is left open to
      air, or suction can be applied to facilitate lobar collapse. The remaining lobe
      of the same lung can be ventilated throughout surgery. Surgery is performed using
      standard VATS techniques. RESULTS: Using this technique we have successfully
      performed VATS on 63 chest sides in 35 patients. The procedures performed
      included thoracodorsal sympathectomies (n = 28), mechanical pleurodesis
      procedures (n = 3), mediastinal and pleural biopsies (n = 2), and lung wedge
      resections (n = 2). We encountered no mortality or morbidity in all cases.
      CONCLUSIONS: This technique is simple and safe and requires no expensive
      disposable devices. Although not essential for most patients undergoing VATS, it
      deserves to be in the armamentarium of the thoracic surgeon. Further studies will
      be required to better define its application in clinical practice.

PMID- 14726080
TI  - Intermittent infusion of 0.25% bupivacaine through an intrapleural catheter for
      post-thoracotomy pain relief.
AB  - BACKGROUND: The present study was designed to evaluate the effectiveness of
      intrapleural 0.25% bupivacaine delivered by intermittent infusions for post
      thoracotomy pain relief. METHODS: Forty patients undergoing elective lobectomy
      were randomly, but equally, placed into two groups. An intrapleural catheter was
      inserted under direct vision during surgery. Group I received intrapleural 40 mL
      of 0.25% bupivacaine, group II was administered 40 mL of saline solution as a
      control group. Diclofenac sodium was administered as an additional analgesic, if
      required. Postoperative pain was evaluated using a visual analog scale (VAS), and
      Prince Henry pain scale. Arterial oxygen saturation, heart rate, and systemic
      arterial pressures were monitored. All observations were recorded 5, 10, 15, 20,
      25, and 30 minutes after the injection, and thereafter at hourly intervals
      through the postoperative 24 hours. RESULTS: The mean analgesia times were 5
      hours and 2 hours in group I and group II, respectively. Therefore, bupivacaine
      administrations were repeated every 6 hours in group I, and saline with
      additional analgesic were administered every 4 hours in group II. The heart rate
      and arterial pressures did not show a significant difference. While the
      additional analgesic requirement was 180 +/- 10 mg/d in group II, there was no
      need for additional analgesic administration in the group I patients. Arterial
      oxygen was significantly higher in group I than in group II. Arterial carbon
      dioxide tension of group II was significantly higher than that of group I. While
      the postoperative atelectasis and pneumonia developed in four patients and one,
      respectively, in group II, no such complication was observed in group I.
      CONCLUSIONS: The easy placement of an intrapleural catheter and better pain
      relief observed in the present study suggest that intermittent pleural infusion
      of 0.25% bupivacaine has proven to be a safe and effective method for relief of
      post-thoracotomy pain.

PMID- 14726081
TI  - The Nuss procedure for pectus excavatum: evolution of techniques and early
      results on 322 patients.
AB  - BACKGROUND: The Nuss procedure is a minimally invasive technique using a
      retrosternal bar to repair pectus excavatum. Although its technical simplicity
      and cosmetic advantages are remarkable, early applications have been limited to
      children with symmetrical pectus excavatum. We report a large single-institution
      experience including technical modifications to correct asymmetric configurations
      and extend the procedure to adult patients. METHODS: We retrospectively reviewed
      322 consecutive patients who underwent repair of pectus excavatum by the Nuss
      technique and its modifications between August 1999 and June 2002. Of the
      patients 251 (78%) were children and 71 (22%) were adults. Precise morphologic
      characterization of the pectus allowed appropriate shaping of the bar to achieve
      a symmetric repair. RESULTS: Of the 322, 185 (57%) had symmetric and 137 (43%)
      had asymmetric pectus excavatum. Within the asymmetric group 71 were eccentric,
      47 were unbalanced, and 19 were combined. Modifications to the shape of the bar
      including asymmetric and seagull bars were developed to deal with these types of
      asymmetry. A double bar or compound bar technique was used in most of the adults.
      Multipoint wire fixations to ribs were utilized to prevent bar rotation.
      Postoperative complications included pneumothorax (n = 24, 7.5%) and bar
      displacement (n = 11, 3.4%). The bar was removed in 42 patients 2 years after the
      initial procedure. CONCLUSIONS: Precise morphologic classification has led to
      modifications of the Nuss technique that facilitate correction of virtually all
      varieties of pectus excavatum including patients with asymmetric varieties and
      adults.

PMID- 14726082
TI  - The use of a lateral stabilizer increases the incidence of wound trouble
      following the Nuss procedure.
AB  - BACKGROUND: A lateral stabilizer has been used to prevent bar displacement during
      the Nuss procedure for pectus excavatum repair in pediatric patients. We
      experienced wound troubles in patients who had a stabilizer placed within them.
      The aim of this study was to examine the effect of a lateral stabilizer and other
      clinical factors on wound troubles after the Nuss procedure. METHODS: 53 patients
      with pectus excavatum underwent repair by the Nuss procedure. Preoperative
      clinical data, operative data, and postoperative complications were examined in
      all patients. RESULTS: A lateral stabilizer was placed in 29 of the 53 patients.
      Short-term results were excellent in 42 patients (79.2%). Postoperative
      complications involved pneumothorax requiring drainage in two patients,
      atelectasis in one patient, pleural effusion in three patients, deterioration of
      scoliosis in one patient, erythema in one patient, persistent pain in two
      patients, bar displacement in four patients, and local wound complications
      (Seroma with dermatitis due to pressure damage) in five patients. All seromas
      with dermatitis due to pressure damage were initially aseptic around lateral
      stabilizers and became infected in four patients after resection of the seroma or
      spontaneous perforation. Removal of both the pectus bar and lateral stabilizer
      was performed in two of those four patients and the lateral stabilizer was
      removed in the other two patients to prevent catastrophic infection such as
      empyema or mediastinitis. The use of a lateral stabilizer increases the incidence
      of wound trouble (p = 0.041). CONCLUSIONS: Although the Nuss procedure has
      evolved into an effective method for pectus excavatum repair, the use of a
      lateral stabilizer increases the incidence of wound difficulties.

PMID- 14726083
TI  - Use of Monogen for pediatric postoperative chylothorax.
AB  - BACKGROUND: Postoperative chylothorax is a potentially serious complication of
      pediatric cardiac surgery. The purpose of this study was to report the use of
      Monogen enteral formula for the management of pediatric postoperative
      chylothorax. METHODS: A retrospective, single-institution 2-year study of all
      patients with a diagnosis of postoperative chylothorax was conducted. Chylothorax
      was diagnosed in 25 patients after a total of 535 cardiac operations in children
      younger than 10 years, for an incidence of 4.7%. Eighteen patients had been given
      Monogen, an enteral low long-chain triglyceride formula, as initial treatment.
      Six had been given total parenteral nutrition. The following variables were
      related to outcome and response to Monogen: age, sex, weight, underlying
      condition, type of surgery, interval between surgery and chylothorax diagnosis,
      duration and daily volume of chyle leak, central venous pressure, residual
      lesions, and weight loss. RESULTS: Enteral feeding with Monogen was successful
      for 14 of 18 patients with a response to treatment evident by the end of the
      third day. No variables predicted which patients would respond to Monogen. Body
      weight was maintained or increased in 14 of the 17 surviving patients taking
      Monogen. A return to normal diet at 4 +/- 1 weeks from the day of pleural drain
      removal did not result in recurrent chylothorax. CONCLUSIONS: A trial of Monogen
      is recommended as initial treatment for postoperative chylothorax unless enteral
      feeding is contraindicated.

PMID- 14726084
TI  - Descending necrotizing mediastinitis: a minimally invasive approach using video
      assisted thoracoscopic surgery.
AB  - BACKGROUND: Descending necrotizing mediastinitis is a rare but serious disease.
      Aggressive surgical approaches have been emphasized rather than simple medical
      treatment. METHODS: Four patients with descending necrotizing mediastinitis were
      treated surgically in our institution between January 2001 and August 2002. Three
      had peritonsilar abscesses and one had an odontogenic abscess. Operative
      procedures included drainage and debridement through a Chamberlain incision and
      neck incision using video-assisted thoracic surgery. RESULTS: The mean duration
      from symptoms to operation was 5.3 days (range, 3 to 7) and mean hospital stay
      was 28.8 days (range, 14 to 47). There was no perioperative mortality.
      Postoperative complications were found in three patents: two with localized
      pleural effusion and one with a hydropneumothorax. CONCLUSIONS: Video-assisted
      thoracic surgery is feasible and effective as a less invasive method for the
      surgical management of patients with descending necrotizing mediastinitis,
      especially when applied early.

PMID- 14726085
TI  - Transfemoral control of ruptured aortic pseudoaneurysm at aortic root
      reoperation.
AB  - Median sternotomy in the setting of aortic pseudoaneurysm and/or rupture is
      hazardous, requiring technical modifications to prevent exsanguination. Free
      aortic disruption, particularly when accompanied by aortic regurgitation,
      presents a particularly challenging situation. The critical issue is to protect
      the brain and heart while obtaining control of the aorta. We report management of
      such a case using transfemoral balloon aortic occlusion.

PMID- 14726086
TI  - Thrombosis of aortic valve homograft associated with lupus anticoagulant
      antibodies.
AB  - One of the main advantages of an aortic valve homograft in comparison with a
      mechanical prosthesis is the low incidence of thromboembolism without
      anticoagulation. Development of an obstructive thrombosis is virtually unknown.
      We report the case of a patient who twice was seen with hemodynamically
      significant thrombosis of an aortic valve homograft. The diagnosis was suspected
      on the basis of a subacute increase in the transvalvular gradient and was
      confirmed by transesophageal echocardiography. Lupus anticoagulant antibodies
      were detected. Oral anticoagulation proved to be effective in relieving the
      obstruction, but recurrence after discontinuation of acenocoumeral suggests that
      treatment should be long term, if not lifelong. To our knowledge, this
      complication of primary antiphospholipid syndrome is the first reported case of
      thrombotic obstruction of an aortic valve homograft.

PMID- 14726087
TI  - Left main stem patch plasty and aortic root homograft in Takayasu's disease.
AB  - Takayasu's arteritis (TA) is a chronic large vessel vasculitis, first described
      in 1908 by the Japanese ophthalmologist Takayasu, affecting more frequently young
      women. The typical lesions represented by aneurysmatic dilatation or
      obliteration, and narrowing of the arterial lumen may pose technical difficulties
      as well as demanding decision making for treatment. Since Jarvell first described
      aortic regurgitation in TA in 1954, unresolved problems still remain for aortic
      valve replacement, particularly because of the young age of these patients. We
      report the case of a 28-year-old woman, with a known history of TA, referred to
      our department.

PMID- 14726088
TI  - Iatrogenic iliac artery rupture and type a dissection after endovascular repair
      of type B aortic dissection.
AB  - We report a case of two iatrogenic complications after endovascular repair of a
      type B aortic dissection treated for abdominal aortic branch ischemia. A rupture
      of the common iliac artery occurred first during the procedure. A type A
      dissection occurred 12 days later. The proximal part of the aortic endovascular
      graft had created a tear in the aortic wall resulting in a retrograde type A
      dissection. Although aortic endovascular grafting is apparently associated with
      less morbidity and mortality, potentially lethal complications, both acute and
      delayed, may arise.

PMID- 14726089
TI  - Composite aortoplasty for recurrent coarctation after neonatal repair in Williams
      syndrome.
AB  - Supravalvar aortic stenosis is the most frequent operation required for Williams
      syndrome; however, coarctation repair is more common in patients requiring
      surgery in the first few months of life. We report on a child with Williams
      syndrome in whom extensive reoperation was required 5 months after neonatal
      aortic coarctation repair. A composite left subclavian artery flap and allograft
      patch aortoplasty of the aortic arch and descending aorta was performed through a
      left thoracotomy using cardiopulmonary bypass and circulatory arrest. Detailed
      anatomic evaluation of the aortic arch and descending aorta is recommended before
      initial coarctation repair in neonates with Williams syndrome.

PMID- 14726090
TI  - Coronary artery obstruction due to membranous ridge of the right sinus valsalva
      associated with Tetralogy of Fallot: syncope mimics anoxic spell.
AB  - We report an infant with Tetralogy of Fallot who had suffered from repetitive
      attacks of syncope without obvious cyanosis. Careful observation by means of
      echocardiography and angiography revealed that the attacks resulted from acute
      coronary artery obstruction due to membranous ridge covering the sinus Valsalva.
      Surgical resection of the abnormal ridge and repair of Tetralogy of Fallot
      successfully improved the patient's symptoms. Syncope in children should be
      extensively investigated to exclude obstruction of the coronary arteries.

PMID- 14726091
TI  - Hemothorax due to extramedullary erythropoietic masses.
AB  - We describe a 27-year-old male patient suffering from beta-thalassemia intermedia
      who presented with a nontraumatic spontaneous hemothorax due to extramedullary
      hemopoietic foci. In reviewing the literature, four similar reports were found.
      The details of this unusual entity are discussed.

PMID- 14726092
TI  - Empyema resulting from a true colopleural fistula complicating a perforated
      sigmoid diverticulum.
AB  - Empyemas developing after traumatic rupture of intraabdominal organs have been
      previously reported. We report a case of a true nontraumatic colopleural fistula
      following surgery for spontaneous rupture of a sigmoid diverticulum. The
      diagnosis was suspected by the presence of an air-containing tract seen in a
      computerized tomogram of chest and abdomen and was established with a contrast
      study. The empyema cavity was initially drained, followed by a laparotomy and
      fistulectomy with primary large bowel anastomosis and loop ileostomy. Although
      rare, colopleural fistulas present a diagnostic challenge and delayed management
      can lead to increased morbidity.

PMID- 14726093
TI  - Closure of bronchopleural fistulas using albumin-glutaraldehyde tissue adhesive.
AB  - Bronchopleural fistulas are a life-threatening complication of pulmonary
      resection. A 21-year-old woman developed a large bronchopleural fistula after
      undergoing a pneumonectomy for carcinoid tumor. Despite bronchial stump revision
      and omental coverage, the fistula recurred. The second patient is a 42-year-old
      woman with a history of multiple thoracotomies who developed a bronchopleural
      fistula following aortic root replacement. Using either rigid bronchoscopy or
      thoracoscopy, these fistulas were evaluated and sealed with an albumin
      glutaraldehyde tissue adhesive that may have improved strength and
      biocompatibility compared with other tissue sealants. This approach may be an
      effective alternative in the treatment of bronchopleural fistulas.

PMID- 14726094
TI  - Closure of an iatrogenic tracheo-esophageal fistula with bronchoscopic gluing in
      a mechanically ventilated adult patient.
AB  - Management of acquired nonmalignant tracheo-esophageal fistula (TEF) in
      mechanically ventilated patients is controversial. Surgical correction is often
      contraindicated because the high operative risk and spontaneous closure is
      unlikely due to the positive pressure ventilation. We present a case of
      successful closure of an iatrogenic TEF in a mechanically ventilated patient with
      bronchoscopic application of fibrin glue. The technique may be proposed in high
      risk patients as either an alternative to surgery or as a first-line attempt
      before surgical correction.

PMID- 14726095
TI  - Solitary eosinophilic granuloma of sternum.
AB  - Primary bone tumors of the chest wall are uncommon, although a wide variety of
      both benign and malignant tumors arise within the chest wall. Among those tumors,
      sternal tumors are rare and usually malignant. We report an extremely rare case
      of eosinophilic granuloma developed in the sternum in a 30-year-old woman. She
      presented anterior chest pain and somewhat tender mass over the sternum. Chest
      roentgenogram, computed tomography scanning of the thorax, and total body bone
      scintigraphy revealed an isolated lytic lesion in the corpus sterni. A tru-cut
      biopsy of the mass exhibited the typical histologic appearance of eosinophilic
      granuloma. The solitary lesion was removed completely surgically. This rare
      condition should be kept in mind in differential diagnosis of sternal lesions.

PMID- 14726096
TI  - Primary chondromatous osteosarcoma of the pulmonary artery.
AB  - Primary pulmonary sarcoma is an extremely rare malignancy, pulmonary osteogenic
      sarcoma is even more rare and has a poor prognosis. We present a report of a 58
      year-old woman with primary pulmonary osteosarcoma occupying the right main
      pulmonary artery and extending to the main pulmonary artery. Right pneumonectomy
      was performed with total right main pulmonary artery resection under
      cardiopulmonary bypass. Microscopic examination demonstrated that tumor cells
      contained mainly chondromatous components and were atypical cells that became
      osteoid. There is no sign of recurrence 24 months postoperatively. The present
      case is the only case yet reported with even an intermediate-term survival
      without recurrence.

PMID- 14726097
TI  - Surgical management of leiomyosarcoma of the mediastinum.
AB  - Leiomyosarcoma of the mediastinum is sufficiently rare; therefore therapeutic
      approaches are not well defined. Current therapy primarily rests with the
      thoracic surgeon. We report a single case of a large leiomyosarcoma of the
      mediastinum invading the heart and right lung. Our diagnostic and therapeutic
      approach to this patient is presented and the pertinent literature is reviewed.
      We conclude that little advancement has been made with regard to adjuvant
      therapies for leiomyosarcoma of the mediastinum, and the only opportunity for
      cure remains with full surgical extirpation.

PMID- 14726098
TI  - Life-threatening hemoptysis in a child: the only symptom.
AB  - An 8-year-old girl was evaluated for hemoptysis, 50 mL/day, which lasted for 3
      days. Computed thoracic tomography detected a mass lesion in the right lower
      lobe. During rigid bronchoscopic examination, exanguinating hemoptysis occurred,
      and a Fogarty balloon catheter was placed in the right intermediate bronchus.
      Thoracotomy revealed a 2 x 2-cm mass in the right lower lobe. Common basal
      segmentectomy was performed. Pathological frozen-section analysis confirmed the
      diagnosis of perforated hydatid cyst.

PMID- 14726100
TI  - Double-patch technique for postinfarction ventricular septal perforation.
AB  - A modified infarct-exclusion technique for postinfarction ventricular septal
      perforation is presented. The perforation is closed directly by a small patch
      next to the conventional patch, and biological glue is applied between the
      patches to induce stable polymerization. The patch stuck to the infarcted septum,
      and no residual shunt was observed in any patient because the wide adhesion
      prevents excessive pressure on the suture line. Seven of 9 patients in whom this
      method was used had good results. This technique appears suited for repair of
      ventricular septal perforations, especially those with extensive fresh
      infarction.

PMID- 14726099
TI  - Application of ET-Kyoto solution in clinical lung transplantation.
AB  - We have developed a new organ preservation solution called extracellular-type
      trehalose-containing Kyoto (ET-Kyoto) solution. ET-Kyoto solution has been
      applied in clinical lung transplantation. The patient was a 49-year-old woman
      with diffuse panbronchiolitis. She underwent bilateral lobar lung transplantation
      from living donors. Each lobe was flushed with ET-Kyoto solution. After
      reperfusion, PaO(2) with inhalation of 100% oxygen was more than 500 Torr.
      Posttransplantation course was uneventful. Despite the relatively short ischemic
      time of this case report, ET-Kyoto solution may be feasible and safely applied in
      clinical lung transplantation.

PMID- 14726101
TI  - Visualization of intramuscular left anterior descending coronary arteries during
      off-pump bypass surgery.
AB  - In off-pump coronary artery bypass surgery, an appropriate method for
      intraoperative evaluation of grafts and vessels has been awaited. We report the
      usefulness of a 15-MHz linear transducer for this purpose. A 15-MHz linear
      transducer with a SONOS 5500 (Philips Medical Systems, Best, Netherlands) was
      applied epicardially in off-pump coronary artery bypass surgery patients.
      Vascular anatomy was easily discerned when the transducer was applied in an
      appropriate way. In 6 patients, intramuscular coronary arteries were easily
      detected, and in all of these patients, anastomoses were successful. The shapes
      of the anastomoses were very clearly shown, and the flow and its phase in the
      bypass graft or coronary artery were measured with synchronization of
      electrocardiograms in all patients. The total left internal thoracic artery
      (LITA) flow (28.4 +/- 6.8 mL/s) and the pattern of the flow was dominantly
      diastolic in all patients. The 15-MHz linear transducer system (Philips) is very
      useful for detecting intramuscular left anterior descending coronary arteries and
      may become one of the standard tools for intraoperative evaluation in off-pump
      coronary artery bypass surgery.

PMID- 14726102
TI  - Implantation of MicroMed DeBakey VAD through left thoracotomy after previous
      median sternotomy operations.
AB  - A left lateral thoracotomy was used for implantation of the continuous-flow
      MicroMed DeBakey left ventricular assist device in 12 patients with previous
      heart operations through a median sternotomy. This approach avoids reopening the
      chest through a median sternotomy and reduces the risk of bleeding and subsequent
      complications.

PMID- 14726103
TI  - Protection of right pneumonectomy bronchial sutures with a pedicled thymus flap.
AB  - A pedicled flap obtained by mobilizing the right lobe of the thymus was used to
      protect bronchial sutures in 29 consecutive patients undergoing a right
      pneumonectomy and in 4 additional patients. Fourteen patients had received
      preoperative chemotherapy with or without radiotherapy. The flap procedure was,
      in general, easy to do, required an average time of 20.4 minutes, and did not
      cause added operative morbidity. Postoperative magnetic resonance imaging,
      performed in 21 of the 29 patients who had pneumonectomy, showed a viable flap in
      every instance. One bronchopleural fistula occurred in a pneumonectomy patient
      after induction chemotherapy plus radiotherapy in a patient in the pneumonectomy
      group in whom adult respiratory distress syndrome developed postoperatively and
      who required prolonged mechanical ventilation.

PMID- 14726104
TI  - Drug immunosuppression therapy for adult heart transplantation. Part 1: immune
      response to allograft and mechanism of action of immunosuppressants.
AB  - In the early days of transplantation, immunosuppression therapy was rather broad
      and nonspecific, mainly using high-dose corticosteroids and azathioprine.
      Thereafter we progressively narrowed the target of immunosuppressive strategy
      starting with polyclonal antibodies. The introduction of cyclosporine, OKT3, and
      tacrolimus further narrowed the target on the T-cell pathways. More recently
      mycophenolate mofetil progressively took the place of azathioprine with its
      higher lymphocyte specificity and sirolimus and interleukin-2 receptor antibodies
      were introduced. In this field in constant movement the aim is to find a drug or
      a regimen that provides optimal immunosuppression therapy with minimal side
      effects, in other words to find the right balance between overimmunosuppression
      and underimmunosuppression therapy. This review is divided into two parts. The
      first part will provide a basic understanding of the immunologic response to
      allograft and explain how conventional and recently introduced immunosuppressive
      agents work. The second part will describe the clinical application of
      immunosuppressive drugs to provide practical information for those in charge of
      heart transplant recipients.

PMID- 14726105
TI  - Drug immunosuppression therapy for adult heart transplantation. Part 2: clinical
      applications and results.
AB  - This review describes the clinical application of classical immunosuppressive
      drugs as well as that of more recent drugs. All current immunosuppressive drugs
      target T-cell activation, and cytokine production and clonal expansion, or both.
      Immunosuppressive protocols can be broadly divided into induction therapy,
      maintenance immunosuppression, and treatment of acute rejection episodes.

PMID- 14726106
TI  - Changing dogmas: history of development in treatment modalities of traumatic
      pneumothorax, hemothorax, and posttraumatic empyema thoracis.
AB  - Development of treatment modalities for chest wounds and traumatic empyema
      thoracis is reviewed in the light of war experience. Mortality from thoracic
      injury was more than 50% before World War I and was about 25% during World War I.
      It came down to 10% in World War II and was about 5% during the Korean War. It
      improved further during the Vietnam War, until it ranged at 2% to 4%, where no
      further improvement could be imagined. Thoracic surgery was born in the field
      hospitals of World War I. Established drainage methods and standardized
      anesthesia made thoracotomy a standard procedure in World War II. As experience
      increased in chest trauma, surgical aggression diminished. Drainage ruled primary
      chest trauma treatment algorithms during the Vietnam War and coexisted with the
      full arsenal of cardiothoracic surgery when it was needed. Optimization of
      thoracic surgical aggression includes a case-tailored approach when major chest
      surgery with or without interventions on the central cardiovascular system is
      needed. This is where we are now, provided a proper logistic, Medevac system
      exists. If we let the past fade away, the danger of committing the mistakes of
      our predecessors increases without having their excuses. Our present is only the
      past of the future.

PMID- 14726107
TI  - Use of internal mammary artery graft in dialysis patients with upper extremity
      arteriovenous fistula.

PMID- 14726109
TI  - Off-pump coronary artery bypass grafting using arterial grafts exclusively:
      aiming for an absolute "no-touch" aortic technique.

PMID- 14726111
TI  - Maze procedure.

PMID- 14726113
TI  - Oncosis rather than apoptosis?

PMID- 14726116
TI  - Pharmacokinetic evaluation of an azithromycin controlled release dosage form in
      healthy human volunteers: a single dose study.
AB  - Azithromycin (AZI) follows a two-compartment model pharmacokinetically. The
      purpose of this study was to evaluate the in vivo performance of a controlled
      release (CR) formulation of AZI, which would eliminate the risk of high peak
      plasma concentrations obtained within 2-3 h after peroral administration of
      immediate release (IR) products. The study was conducted in twelve healthy male
      human volunteers to compare an experimental NIPER product (CR tablets) with Vicon
      (IR tablets) at the same dose level as a single-dose, randomized, one-period, two
      treatment, and parallel-study. Concentrations of AZI in serum samples were
      assessed using the validated HPLC method. From the serum concentration-time
      profiles various pharmacokinetic parameters (AUC(0-96), AUC(0-inf), C(max) and
      T(max)) were calculated for both products. Results showed that the high peak
      concentration obtained by administration of a conventional IR formulation were
      eliminated with the CR product. A mean dosage form index (DI) of 1.17 with
      fluctuations of 7.57% was obtained with the CR product at steady state level,
      indicating reduced fluctuations at the steady state serum concentrations.
      Elimination of the pronounced peak as well as fluctuations reduced or minimized
      AZI adverse effects associated with the IR product.

PMID- 14726117
TI  - Analysis of formulation effects in the dissolution of ibuprofen pellets.
AB  - In this work the effects of citric acid and of two common fillers, lactose
      (soluble) and tricalcium phosphate (insoluble) are examined on the release
      profiles from pellets, using ibuprofen as a model drug with pH-dependent
      solubility. Also studied is the dependence of these profiles on the specific
      surface area, bulk density, apparent density, porosity and porosity parameters
      (pore size distribution, total pore surface area, mean pore diameter and pore
      shape), as determined by mercury intrusion porosimetry. Pellets with high
      porosity and total pore surface area but small median pore diameter (tricalcium
      phosphate pellets-IPM) are found to produce similar dissolution results to those
      of low porosity and low total pore surface area, but having a high median pore
      diameter (lactose pellets-ILM), irrespective of the solubility of excipients.
      Addition of citric acid causes a delay in the initial dissolution for both
      formulations. During dissolution, however, citric acid reduces the median pore
      diameter of lactose-based pellets. In contrast, in tricalcium phosphate/citric
      acid pellets (CIPM), this parameter increases considerably during dissolution,
      when compared to the IPM formulation. These findings may justify the contrasting
      dissolution behaviors of CIPM and CILM (lactose/citric acid) pellets, after their
      common behavior in the initial stages, and show that porosity and its related
      parameters, along with physical properties of excipients such as solubility,
      density and specific surface area, are helpful to predict pellet behavior in drug
      release profiles.

PMID- 14726118
TI  - New screening method for the determination of stability of pharmaceuticals.
AB  - A rapid method for obtaining the parameters describing the lengths of oxidation
      induction periods from non-isothermal differential scanning calorimetry
      measurements, based on the dependence of onset temperature of the oxidation peak
      on heating rate, is presented. The method has been applied for screening the
      stability of a set of three pharmaceuticals. The order of stabilities of the
      compounds obtained by the method coincides with the order determined by classical
      stability tests.

PMID- 14726119
TI  - Evaluation of new rosin derivatives for pharmaceutical coating.
AB  - Rosin and Rosin-based polymers have diversified drug delivery applications
      achieving sustained/controlled release profiles. In this manuscript, two new
      Rosin derivatives were synthesized and evaluated for physicochemical properties,
      molecular weight, polydispersity and glass transition temperature. Plasticizer
      free films prepared by solvent evaporation were tested for surface morphology,
      water vapour transmission and mechanical properties (tensile strength, percent
      elongation and modulus of elasticity). The films showed low tensile strength and
      high percent elongation values achieving smooth and uniform surface. The
      derivatives were further characterized for film coating by evaluating the release
      of a model drug (diclofenac sodium) from pellets coated with the rosin
      derivatives as retarding membrane. Drug release was sustained up to 10 h due to
      10% (w/w) coat built up with the new rosin derivatives. Increase in coat-built-up
      further facilitated sustained release from coated forms. Film coating could be
      achieved without agglomeration of the pellets within a reasonable operating time.
      The present study proposes novel film forming materials with potential use in
      sustained drug delivery.

PMID- 14726120
TI  - Pluronic gels for nasal delivery of Vitamin B12. Part I: preformulation study.
AB  - Thermoreversible nasal gels of Vitamin B(12) using pluronic PF 127 were aimed to
      improve absorption and patient compliance. In the present research work, effects
      of Vitamin B(12) and gel additives, viz. PF concentration, osmolarity,
      polyethylene glycol (PEG 15000) on thermodynamic properties of phase transitions
      at gelation (T(1)) and gel melting (T(2)) is reported. Aqueous PF 127 gels
      prepared by cold method containing pluronic (20-24%, w/w), vitamin, sorbitol,
      PEG, and benzalkonium chloride. T(1) decreases and T(2) increases with vitamin
      and PF concentration. Gelation range narrows with sorbitol and PEG. Suppression
      of T(2) is significantly higher than T(1) with both the additives. The linearity
      was observed only for semilogarithmic plot of PF concentration and 1/T(2) for
      sorbitol and PEG, which reveals significant interaction of both at gel melting.
      Enthalpy of both transitions remains unchanged with vitamin indicating no
      interaction with polymer. Benzalkonium chloride decreased gelation onset
      temperature. Thermodynamic properties of PF 127 gels are significantly altered
      with polymer concentration and water-soluble formulation additives.

PMID- 14726121
TI  - Electron beam irradiation: a novel technology for the development of transdermal
      system of isosorbide dinitrate.
AB  - The development of a transdermal delivery system for isosorbide dinitrate (ISDN)
      using electron beam irradiation was studied. The solid state stability of the
      drug to irradiation was assessed. The drug was dissolved in 2-ethylhexylacrylate
      (EHA)-acrylic acid (AA) system and this solution was directly irradiated on a
      backing membrane (Scotchpak1006) at different doses to get transdermal patches.
      The developed systems were evaluated for residual monomer content, equilibrium
      weight swelling ratios (EWSR), differential scanning calorimetry (DSC), weight
      uniformity, thickness uniformity, drug content and content uniformity, peel
      strength, in vitro release, skin permeation kinetics and skin irritation
      potential. The developed system possessed excellent adhesive properties. Increase
      in the irradiation doses did not have a significant effect on the peel strength
      values. The systems exhibited promising skin permeation kinetics and no skin
      irritating potential, both of which are important properties for transdermal drug
      delivery. The ISDN-EHA-AA system developed at an irradiation dose of 50 kGy
      showed a higher skin permeation profile as compared to an internationally
      marketed transdermal matrix system of ISDN.

PMID- 14726122
TI  - In vitro release of Tacrolimus from Tacrolimus ointment and its speculated
      mechanism.
AB  - The in vitro release profiles and the bleeding phenomenon of Tacrolimus and
      propylene carbonate (PC) as a dispersing solvent for Tacrolimus drug substance in
      Tacrolimus ointment were investigated when changing concentrations of Tacrolimus
      and PC in the ointment were used, respectively. The bleeding test result
      indicated that Tacrolimus was in equilibrium between inside and outside of PC
      droplets in intact ointment base. A cumulative release amount of Tacrolimus from
      ointment, plotted against the square root of time, showed a straight line
      initially with a slope of q1 followed to change a slope to be q2 at a certain
      time, where the relation of these slopes being q1<q2. The q1 values increased
      with the concentration of Tacrolimus but decreased with PC concentration in
      Tacrolimus ointment. And the q2 values increased with Tacrolimus concentration
      but were independent of PC concentration. These profiles indicated that there
      were two phases for Tacrolimus release from ointment, namely, first phase was
      related with the period during PC release and the second phase was related with
      the state of ointment after PC release. When the PC release was applied to the
      Higuchi's release equation, the above slope q1 was found to be correlated to the
      parameter of A/phi(0), where A was a parameter of release rate of PC and phi(0)
      was an initial volume fraction of PC droplets. It should be indicated that more
      rapid release rate of PC rather than that of Tacrolimus resulted in the
      generation of amorphous phase of Tacrolimus outside of remaining PC droplets.
      During PC release, the slope q1 could be influenced by the thermodynamic activity
      of Tacrolimus dissolved in PC droplets. After PC release, it would be reasonable
      to speculate that the amorphous cluster of Tacrolimus with a constant
      thermodynamic activity would give constant q2 values regardless of PC contents in
      Tacrolimus ointment.

PMID- 14726123
TI  - MIN6 cells-enclosing aminopropyl-silicate membrane templated by alginate gels
      differences in guluronic acid content.
AB  - Mouse insulinoma (MIN6) cells were encapsulated into aminopropyl-silicate
      membrane deposited on calcium alginate gel beads via the sol-gel synthesis. Two
      alginates with different guluronic acid (G) contents, high and intermediate, but
      with the same molecular weights were used. Viability of the cells in the membrane
      templated by the alginate with an intermediate content of guluronic acid
      (intermediate-G) was approximately 10% higher than those in the membrane
      templated by the alginate with a high content of guluronic acid immediately after
      encapsulation. Growth of cells in vitro was hindered in case of encapsulation in
      the aminopropyl-silicate membrane deposited on the high-G alginate gel. The MIN6
      cells in the microcapsule made from high-G alginate needed a longer period to
      establish a normoglycemic in recipients than those in the microcapsule made from
      intermediate-G alginate despite the same number of viable cells implantation.
      Recipients of the microcapsule with the core made from the intermediate-G
      alginate maintained their blood glucose values less than 300 mg/dl for a longer
      period.

PMID- 14726124
TI  - Comparative study between the interaction of dephosphorylated amifostine (WR
      1065) and amoxicilline with pBR322 in absence and presence of cisplatin by AFM.
AB  - The effect of the amoxicilline as a possible cisplatin-action protector on pBR322
      DNA has been visually studied by atomic force microscopy in comparison with the
      modifications caused by the controversed cisplatin protector amifostine.
      Incubation of amoxicilline with the plasmid DNA showed aggregation and compaction
      of DNA. Cisplatin incubated in the same conditions with DNA produced kinks and
      super-coiling of the circular form. In the case of previous treatment of DNA with
      amoxicilline, the characteristic effect of cisplatin is only partially observed.
      The amoxicilline seemed to control the action of cisplatin on DNA. The initial
      effect of dephosphorylated amifostine (WR-1065) when this protector was incubated
      with the plasmid was also the formation of aggregates and the compaction of DNA.
      However, addition of cisplatin successively after 1 and 2 h showed the
      characteristic modification caused by cisplatin but only in a decreasing
      percentage of molecules of DNA. Both molecules, amoxicilline and WR-1065 seem to
      control the strong direct action of cisplatin on DNA. This effect can justify the
      role as protecting agent of amifostine on side effects caused by cisplatin and
      can open new possibilities to other agents like amoxicilline.

PMID- 14726125
TI  - In vivo study of different ointments for drug delivery into oral mucosa by EPR
      oximetry.
AB  - The aim of the present study was to determine the rate of transport and long-term
      effect of a drug applied to the oral mucosa in different ointments. Three
      ointments with bioadhesive properties: Orabase, Carbopol 935P, and polymethyl
      methacrylate (PMM) and the ointment Miglyol without such properties were used.
      Benzyl nicotinate (BN) was used as an active ingredient that causes hyperemia.
      The kinetics of drug action was measured by electron paramagnetic resonance (EPR)
      oximetry in vivo using the paramagnetic probe (Lithium phthalocyanine) implanted
      beneath the epithelium of the buccal mucosa in rats. EPR spectra line-width was
      proportional to local changes of partial pressure of oxygen (pO(2)) in tissue and
      was monitored for 90 min after the application of ointments mixed with BN. The
      greatest increase in pO(2) and the highest efficiency of drug action was observed
      after the application of 2% BN in PMM (P<0.01). Additionally in PMM the drug
      effect increased linearly with BN concentration up to 3%, at higher
      concentrations (3.5 and 4% BN) no further effect was observed. The results
      demonstrated that the greatest and the longest effect caused by a hyperemic drug
      in PMM. By increasing the concentration of the drug in PMM higher pO(2) in the
      oral mucosa can be established but only until the saturation is reached.

PMID- 14726126
TI  - Development and characterization of a novel liposome-based formulation of SN-38.
AB  - SN-38, 7-ethyl-10-hydroxycamptothecin, is the active metabolite of Irinotecan
      (CPT-11), a topoisomerase I inhibitor commercially available as Camptosar. SN-38
      is approximately 200-2000-fold more cytotoxic than CPT-11. Despite its promising
      anticancer potential, SN-38 thus far has not been used as an anticancer drug due
      to its poor solubility in any pharmaceutically acceptable solvents. In addition,
      SN-38 has low affinity to lipid membranes; it tends to precipitate in aqueous
      phase resulting in a very low drug-to-liposome entrapment. SN-38 also reversibly
      converts to an inactive open lactone ring structure at physiological pH. We have
      developed a novel, liposome-based SN-38 formulation (LE-SN-38). The formulation
      contains liposomes of uniform size distribution (<200nm), and it is easy-to-use.
      Drug entrapment efficiency of the formulation is >95%. Long-term stability
      studies indicate that the lyophilized LE-SN-38 is physically and chemically
      stable for at least 6 months at 2-8 degrees C. In preclinical studies, LE-SN38
      has shown promising results in terms of increased cytotoxicity against various
      tumor cell lines and better therapeutic efficacy towards xenograft mouse models
      compared to CPT-11.

PMID- 14726127
TI  - Intestinal absorption of penclomedine from lipid vehicles in the conscious rat:
      contribution of emulsification versus digestibility.
AB  - While the inclusion of highly lipophilic compounds in self-emulsifying drug
      delivery systems (SEDDS) is often reported to result in strongly enhanced oral
      absorption, it is still controversial whether further lipolysis of the dispersed
      lipidic material is required for final transfer to the enterocyte membranes. In
      order to assess the relative roles of lipid vehicle dispersion and vehicle
      digestibility in the oral absorption of penclomedine (Pcm), a series of
      formulations of Pcm in medium chain triglyceride (MCT)/tocophersolan (TPGS) was
      developed having three sizes (160 nm, 720 nm, and mm-sized ('crude' oil)); with
      or without the inclusion of tetrahydrolipstatin (THL), a known lipase-inhibitor.
      Oral absorption of Pcm was studied after administration of small volumes of these
      formulations in the conscious rat. Kinetic evaluation was performed using
      population analysis. Formulations with particle size 160 nm had the highest
      relative bioavailability (set at F=1), whereas administration in particle size
      720 nm had slightly lower bioavailability (F=0.79). Co-inclusion of THL yielded
      similar bioavailability for these two SEDDS. 'Crude' oil formulations had F=0.62
      (without THL) and 0.25 (with THL). The data in the current investigation
      emphasize the prominent role of increased vehicle dispersion relative to
      digestibility in the absorption of Pcm from MCT-TPGS in submicron emulsions. Only
      with Pcm administered as undispersed MCT, absorption was more dependent on the
      action of lipase as bioavailability was inhibited two-fold by the co
      incorporation of THL.

PMID- 14726128
TI  - Deformable liposomes for dermal administration of methotrexate.
AB  - Deformable liposomes were prepared to investigate the effectiveness of dermal
      administration of methotrexate (MTX). The phospholipids used to prepare the
      liposomes were soybean lecithin (PC) or hydrogenated lecithin (HPC) and
      dipotassium glycyrrhizinate (KG) as surfactant. The lipid/KG ratio (w/w) was 2:1
      and 4:1. Liposomes size, entrapment efficiency and MTX release through dialysis
      membrane were determined and the interaction between MTX and liposomes was
      investigated using differential scanning calorimetry. The MTX amount permeated
      through pig skin were three- to four-fold higher using liposomes containing KG
      compared to those from water solution or normal liposomes. No significant
      differences were observed between PC-KG liposomes and HPC-KG liposomes. At the
      end of the skin permeation assay using deformable liposomes, up to 50% of the
      administered dose was found in the skin. This capability depends on the self
      regulating carrier deformability. These results suggest that liposomes containing
      KG may be of value for the topical administration of MTX in the treatment of
      psoriasis.

PMID- 14726129
TI  - Electroporation-mediated delivery of molecules to model intestinal epithelia.
AB  - This study was conducted to determine if electroporation can deliver membrane
      impermeant molecules intracellularly to intact, physiologically competent
      monolayers that mimic the intestinal epithelium. In addition, the long-term
      effects of electroporation on these monolayers were studied to determine the
      kinetics with which monolayers recover barrier function. Caco-2 and T84 cells
      were electroporated as monolayers using calcein and fluorescein-labeled bovine
      serum albumin as marker molecules for measuring delivery into cells. Confocal
      microscopy and flow cytometry were used, respectively, to visualize and quantify
      uptake of these molecules. Transepithelial resistance was used as a measure of
      physiologic barrier function. We found that intracellular uptake of calcein and
      bovine serum albumin occurred uniformly throughout both types of model epithelia
      and increased as a function of voltage, pulse length, and pulse number. There was
      no significant difference in uptake resulting from single and multiple pulses of
      the same total exposure time. We also observed that monolayers exposed to
      electroporation that induced uptake of up to 10(6) molecules/cell were able to
      recover normal barrier function within one day. These findings suggest that
      electroporation may be useful for intracellular delivery into monolayers to study
      epithelial biology and, possibly, for drug delivery to intestinal epithelium.

PMID- 14726130
TI  - Flow and injection characteristics of pharmaceutical parenteral formulations
      using a micro-capillary rheometer.
AB  - A micro-capillary rheometer consisted of a fine needle with an internal diameter
      of 347 microm attached to a 1 ml removable-needle syringe within an Instron
      device that operated in compression mode to provide various crosshead speeds
      ranging from 150 to 950 mm min(-1) covering typical clinical injection rates, and
      that determined the resulting force on the plunger. The crosshead speed and the
      resulting force were used to calculate the shear rate and the shear stress
      respectively. These were used in standard capillary flow expressions together
      with an independent measurement of the wall frictional force and allowed the
      viscosity of parenteral Newtonian solutions and non-Newtonian suspensions to be
      measured quantitatively and their rheological behaviour in needles of clinical
      dimensions to be established. Commercial pharmaceutical parenteral formulations
      consisting of three oil-based solutions and three aqueous suspensions were chosen
      for this study. The net injection forces were also obtained and it was shown that
      both the oil-based solutions and the aqueous suspensions covered similar ranges.
      The viscosities for the parenteral solutions were determined from the slope of
      the linear regression (R(2)>0.97) between shear stress and shear rate and ranged
      between 0.029 and 0.060 Pas. For the aqueous suspensions examined, viscosities
      decreased from low shear rate to high shear rate, following a power-law model and
      indicating a pseudo plastic behaviour. Standardisation of the micro-capillary
      rheometer with Newtonian silicone oils calibrated with a Rheometrics Fluids
      Spectrometer showed viscosity values consistent between the rotational flow
      measurements and capillary flow measurements which were within 5% and showed very
      high degrees of reproducibility between replicate samples. This degree of
      reproducibility allowed differences in the contribution of the wall frictional
      force to the required plunger force for both the oil-based and aqueous parenteral
      formulations to be determined reliably. The wall frictional force values for all
      formulations were similar (0.6-1.6 N) but the frictional forces of aqueous
      systems were found to decline significantly with plunger speed. The micro
      capillary rheometer has been used to evaluate the impact of concentration changes
      due to sedimentation on the injectability of one of the aqueous suspensions,
      where it was shown that not only the viscosity increased but the shear thinning
      behaviour ceased at higher shear rates. The micro-capillary rheometer which was
      able to operate in clinical shear rate ranges has been shown to detect
      deteriorations in the injectable rheology of suspensions, which in the case here
      was due to pre-injection sedimentation.

PMID- 14726131
TI  - The physicochemical characteristics and bioavailability of indomethacin from beta
      cyclodextrin, hydroxyethyl-beta-cyclodextrin, and hydroxypropyl-beta-cyclodextrin
      complexes.
AB  - In an effort to improve the bioavailability of the insoluble drug indomethacin,
      three complexes were prepared with indomethacin and the soluble complexing agents
      beta-, hydroxyethyl-beta-, and hydroxypropyl-beta-cyclodextrin. The indomethacin
      content was similar among the complexes (P</=0.05). To confirm complex formation,
      each complex was characterized by ultraviolet, infrared, nuclear-magnetic
      resonance, powder X-ray diffraction, and differential-scanning calorimetry
      techniques. Powder diffraction studies show the beta-cyclodextrin complex was
      polycrystalline, and the hydroxyethyl- and hydroxypropyl-beta-cyclodextrin
      complexes were amorphous. Phase-solubility analysis confirmed the formation of
      complexes and suggested the three complexes were bound similarly. Solubility
      studies show complexation increased indomethacin solubility, and the hydroxyethyl
      and hydroxypropyl-beta-cyclodextrin complexes were more soluble than the beta
      cyclodextrin complex in 0.1 N hydrochloric acid and distilled water. Dosage forms
      were prepared by encapsulating the complexes without the addition of excipients.
      Dissolution studies show the encapsulated beta- and hydroxyethyl-beta
      cyclodextrin complexes had superior dissolution when compared to the
      hydroxypropyl-beta-cyclodextrin and Indocin (50 mg) capsules. Bioavailability
      studies were performed by administering the indomethacin complex or Indocin
      capsules to male-albino, New Zealand rabbits. Indomethacin plasma-time
      concentration data fit best to a compartment-independent model for all capsule
      formulations. Bioavailability comparisons by ANOVA show no significant difference
      (P</=0.10) in the peak-plasma time and peak concentration among the capsule
      formulations. The area-under-the-curve for the beta-cyclodextrin complex capsules
      was found to be significantly higher (P</=0.10) than all other capsule
      formulations. In conclusion, the bioavailabilty of indomethacin was improved by
      complexation with only beta-cyclodextrin. No correlations were found among the
      bioavailability, solubility, and dissolution results.

PMID- 14726132
TI  - Theophylline particle design using chitosan by the spray drying.
AB  - Solid dispersions of theophylline with chitosan as a carrier were prepared using
      a spray-drying method. Chitosan dissolved in an acid solution forms a gel, but it
      does not dissolve in an alkaline solution. Therefore, drugs which form composite
      particles with chitosan would gradually be released in an acid solution, and are
      expected to have considerably sustained release in an alkaline solution. In this
      study, we aimed to apply this ability to sustained release pharmaceutics. In this
      study, we used theophylline as a model drug and chitosan as a carrier. Mixtures
      of chitosan and the drug in prescribed ratios were dissolved in an acid solution.
      The physicochemical properties of the solid dispersions obtained were
      investigated by powder X-ray diffraction, differential scanning calorimetry, and
      dissolution rate analyses, with a view to clarify the effect of crystallinity on
      the dissolution rate. Furthermore, the interaction between the drug and the
      carrier was investigated by FT-IR analysis. The powder X-ray diffraction
      intensity of the drug in the spray-dried samples decreased with an increase in
      chitosan contents, which also caused changes from crystalline to amorphous forms.
      These results indicated that the system formed a solid dispersion. The
      dissolution profiles of the drug from the physical mixtures and solid dispersions
      were almost the same at pH 1.2. However, at pH 6.8, the release from the solid
      dispersions was sustained more than that from the physical mixtures. The FT-IR
      spectroscopy for the theophylline solid dispersions suggested that the carbonyl
      group of theophylline and the amino group of chitosan formed a hydrogen bond.
      Mass median aerodynamic diameter (MMAD) was measured by using a cascade impactor
      to evaluate the possibility of solid dispersions as dry powder inhalations. The
      MMAD of the spray-dried theophylline-chitosan systems were 4.5-5.0 microm. The
      results suggested that the spray-drying method is usefull to produce dry powders
      for inhalation.

PMID- 14726133
TI  - Synergism in gene delivery by small PEIs and three different nonviral vectors.
AB  - We have reported earlier that a combination of low-molecular weight
      polyethylenimines (PEIs) with the cationic liposome, Dosper, results in a
      synergistic increase in the transfection efficiency. Now we have investigated
      whether this synergism is a general mechanism seen with other transfection
      reagents as well. Therefore, we have combined the low-molecular weight PEIs (MW
      700 and 2000) with Dotap (a monocationic liposome), Lipofectamine (a combination
      of neutral and polycationic liposome), and Superfect (a dendrimer). The highest
      synergism was achieved with Lipofectamine and PEIs in the SMC cells, or with
      Dotap and PEIs in the C6 cells. Superfect did not induce any synergism. The
      combinations did not cause any changes in DNA condensing ability measured with
      ethidium bromide exclusions. The proton pump inhibitor, bafilomycin A1, had
      similar effects in both cell lines. Interestingly, the combination of Dosper (a
      positive control) and PEI caused the most effective transfection synergism in the
      presence of serum, although Lipofectamine, with or without PEIs, was a very
      potent reagent demonstrating the best transfection efficiency in the absence of
      serum. It is suggested that the PEI/Dosper-mediated synergism in the transfection
      efficiency may be a general mechanism for liposomal transfection reagents,
      although the effects can vary depending on cell lines.

PMID- 14726134
TI  - The characterization of novel polymeric paste formulations for intratumoral
      delivery.
AB  - The objective of this work was to characterize a polymeric paste formulation of
      the anticancer drug paclitaxel that was injectable through a narrow gauge needle
      at room temperature and set to a solid implant in vivo for the intratumoral
      treatment of localized cancer. Pastes were manufactured from a triblock copolymer
      composed of poly(D,L-lactide-co-caprolactone)-block-polyethylene glycol-block
      poly(D,L-lactide-co-caprolactone) (PLC-PEG-PLC) or triblock blended with a low
      molecular weight polymer methoxypolyethylene glycol (MePEG). Characterization of
      pastes was performed using differential scanning calorimetry (DSC), gel
      permeation chromatography (GPC) and drug release studies. Paste integrity in
      water was measured by determining the degree of fragmentation under initial
      agitation. MePEG was found to be miscible with the triblock polymer and
      paclitaxel dissolved in various blends of these polymers up to 15% drug loading.
      Pastes composed of 40:60 triblock:MePEG blends and 10% paclitaxel were found to
      inject through a 23-gauge needle and set to a solid pellet in phosphate-buffered
      saline at 37 degrees C. Such pellets released paclitaxel in a controlled manner
      over 7 weeks. Pastes composed of 40:60 triblock:MePEG blends containing 10%
      paclitaxel are proposed as suitable injectable formulations of the drug for
      intratumoral therapy.

PMID- 14726135
TI  - Poly(dimethylsiloxane) coatings for controlled drug release--polymer
      modifications.
AB  - Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were
      studied for their ability to be applied onto tablet cores in a spray-coating
      process and to control drug release in zero-order fashion. Modifications of the
      crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the
      trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture
      of the two were undertaken. Addition of methylpolysiloxane-copolymers were
      studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000
      (PEG) were the channeling agents applied. The effects on dispersion properties
      were characterized by particle size distribution and viscosity. Mechanical
      properties of resulting free films were studied to determine applicability in a
      pan-coating process. Release of hydrochlorothiazide (marker drug) was studied
      from tablets coated in a lab-size conventional coating pan. All dispersions were
      found suitable for a spray-coating process. Preparation of free films showed that
      copolymer addition was not possible due to great decline in mechanical
      properties. Tablets coated with formulations containing PEG were most suitable to
      control drug release, at only 5% coating weight. Constant release rates could be
      achieved for formulations with up to 25% PEG; higher amounts resulted in a non
      linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h
      could be achieved.

PMID- 14726136
TI  - Pharmacokinetic parameter prediction from drug structure using artificial neural
      networks.
AB  - Simple methods for determining the human pharmacokinetics of known and unknown
      drug-like compounds is a much sought-after goal in the pharmaceutical industry.
      The current study made use of artificial neural networks (ANNs) for the
      prediction of clearances, fraction bound to plasma proteins, and volume of
      distribution of a series of structurally diverse compounds. A number of
      theoretical descriptors were generated from the drug structures and both
      automated and manual pruning were used to derive optimal subsets of descriptors
      for quantitative structure-pharmacokinetic relationship models. Models were
      trained on one set of compounds and validated with another. Absolute predicted
      ability was evaluated using a further independent test set of compounds.
      Correlations for test compounds ranged from 0.855 to 0.992. Predicted values
      agreed closely with experimental values for total clearance, renal clearance, and
      volume of distribution, while predictions for protein binding were encouraging.
      The combination of descriptor generation, ANNs, and the speed and success of this
      technique compared with conventional methods shows strong potential for use in
      pharmaceutical product development.

PMID- 14726137
TI  - Feasibility studies of utilizing disk intrinsic dissolution rate to classify
      drugs.
AB  - The purpose of this report was to investigate the feasibility of using disk
      intrinsic dissolution rate (DIDR) to determine solubility class membership. We
      employed a VanKel dissolution apparatus fitted with a Wood's intrinsic
      dissolution die. To test the robustness of the method, variations of DIDR with
      compression force, dissolution volume, distance of the drug disk from the bottom
      of the dissolution vessel, and drug disk rotation speed were studied using
      furosemide and metoprolol in pH 4.5 acetate buffer as a model system. The DIDRs
      of six low solubility and nine high solubility model drugs were then determined
      at pH 1.2, 4.5, and 6.8 and compared to their BCS solubility class membership. It
      was found that the compression force, dissolution medium volume, and die position
      had no significant effect on DIDR for the system studied. The proposed
      compression force, dissolution volume, die position, and rotation speed are 2000
      psi, 900 ml, 0.5 in., and 100 rpm, respectively. The test results obtained from
      15 model BCS drugs show a good relationship between the DIDR and BCS solubility
      classification with 0.1 mg/min/cm(2) as a class boundary unless the dose is
      either extremely low or high where discrepancies may exist between the solubility
      and DIDR methods. Therefore, more scientific research and debates are needed
      before considered for regulatory purpose.

PMID- 14726138
TI  - Pseudo-ternary phase diagrams of aqueous mixtures of Quil A, cholesterol and
      phospholipid prepared by the lipid-film hydration method.
AB  - Pseudo-ternary phase diagrams of the polar lipids Quil A, cholesterol (Chol) and
      phosphatidylcholine (PC) in aqueous mixtures prepared by the lipid film hydration
      method (where dried lipid film of phospholipids and cholesterol are hydrated by
      an aqueous solution of Quil A) were investigated in terms of the types of
      particulate structures formed therein. Negative staining transmission electron
      microscopy and polarized light microscopy were used to characterize the colloidal
      and coarse dispersed particles present in the systems. Pseudo-ternary phase
      diagrams were established for lipid mixtures hydrated in water and in Tris buffer
      (pH 7.4). The effect of equilibration time was also studied with respect to
      systems hydrated in water where the samples were stored for 2 months at 4 degrees
      C. Depending on the mass ratio of Quil A, Chol and PC in the systems, various
      colloidal particles including ISCOM matrices, liposomes, ring-like micelles and
      worm-like micelles were observed. Other colloidal particles were also observed as
      minor structures in the presence of these predominant colloids including helices,
      layered structures and lamellae (hexagonal pattern of ring-like micelles). In
      terms of the conditions which appeared to promote the formation of ISCOM
      matrices, the area of the phase diagrams associated with systems containing these
      structures increased in the order: hydrated in water/short equilibration
      period<hydrated in buffer/short equilibration period<hydrated in water/prolonged
      equilibration period. ISCOM matrices appeared to form over time from samples,
      which initially contained a high concentration of ring-like micelles suggesting
      that these colloidal structures may be precursors to ISCOM matrix formation.
      Helices were also frequently found in samples containing ISCOM matrices as a
      minor colloidal structure. Equilibration time and presence of buffer salts also
      promoted the formation of liposomes in systems not containing Quil A. These
      parameters however, did not appear to significantly affect the occurrence and
      predominance of other structures present in the pseudo-binary systems containing
      Quil A. Pseudo-ternary phase diagrams of PC, Chol and Quil A are important to
      identify combinations which will produce different colloidal structures,
      particularly ISCOM matrices, by the method of lipid film hydration. Colloidal
      structures comprising these three components are readily prepared by hydration of
      dried lipid films and may have application in vaccine delivery where the
      functionality of ISCOMs has clearly been demonstrated.

PMID- 14726139
TI  - Transdermal iontophoresis of 5-fluorouracil combined with electroporation and
      laser treatment.
AB  - The influence of iontophoresis and other physical enhancement methods such as
      electroporation and erbium:yttrium-aluminum-garnet (YAG) laser on the skin
      permeation of 5-fluorouracil (5-FU) was examined. Iontophoresis increased the in
      vitro transdermal transport of both the anionic and non-ionic forms of 5-FU. A
      combination of electroporation pretreatment and subsequent iontophoresis resulted
      in a higher permeation of 5-FU than either technique alone. It appeared that
      electroporation treatment exerted a disruptive influence on the stratum corneum
      (SC). The SC layers in the skin were partly ablated by the laser, resulting in a
      great enhancement effect on the skin permeation of 5-FU. Application of
      iontophoresis further increased the drug permeation across laser-pretreated skin.
      The laser was consistently the most potent technique to enhance 5-FU delivery
      among the physical enhancement methods examined in this study.

PMID- 14726140
TI  - Effect of different ratios of high and low molecular weight PLGA blend on the
      characteristics of pentamidine microcapsules.
AB  - Two different PLGA samples (Resomer 502 and Resomer 506), either alone or in
      combinations, were used to prepare microcapsules. Microcapsules were prepared
      using a double emulsion solvent evaporation technique. The efficiency of
      encapsulation increased significantly when a mixture of 1 part Resomer 506 and 7
      parts Resomer 502 was used to prepare the microcapsules. The efficiency of
      encapsulation of this batch was 23.7%, whereas the efficiency of encapsulations
      was only 13.9 and 9.8%, respectively, when the microcapsules were prepared with
      100% Resomer 502 or 100% Resomer 506. In contrast, irrespective of the relative
      ratio of Resomer 502/Resomer 506, the median particle size of the microcapsules
      showed similar distribution pattern with the median size lies between 49 and
      83microm. The glass transition temperature (T(g)) decreased significantly (44.6
      25.5 degrees C) as the amount of Resomer 502 was increased in the formulation.
      The presence of Resomer 502 at lower concentration, along with Resomer 506,
      initially reduced the "burst effect." However, incorporation of a higher amount
      of Resomer 502 increased the "burst effect." Drug release from these
      microcapsules continued over 80 days. In conclusion, efficiency of encapsulation
      increased significantly when Resomer 506 was mixed with Resomer 502 at a ratio of
      1:7. Blending of Resomer 502 with Resomer 506 reduced the glass transition
      temperature, which resulted in higher amount of drug release throughout the
      dissolution study.

PMID- 14726141
TI  - The effect of agitated drying on the morphology of L-threonine (needle-like)
      crystals.
AB  - Experiments have been carried out to study the behavior of L-threonine (needle
      like) crystals during agitated drying. For an L-threonine/water system the
      morphology of the crystals was monitored using light microscopy and image
      analysis. Analysis of the transient behavior of the crystal size and shape
      distribution showed that attrition and agglomeration took place simultaneously
      during the process. The variation of the operating conditions (temperature,
      agitation and vacuum) revealed that attrition dominated the drying process when
      the drying rate was low and/or the shear rate was high. For high drying rates and
      low shear rates, agglomeration became dominant. This study suggests that crystal
      redissolution had no significant impact on crystal morphology. It was also found
      that due to their needle-like shape, large L-threonine crystals were very
      sensitive to attrition. When attrition controlled the drying process, most of the
      particle size reduction took place below a critical moisture content of 4%. When
      agglomeration controlled the drying process, most of the crystal size enlargement
      occurred below a moisture content of 6%.

PMID- 14726142
TI  - Stability and transdermal absorption of topical amphotericin B liposome
      formulations.
AB  - The aim os this study was to characterize the stability and transdermal
      absorption of amphotericin B (AMB: 0.05 mg/mg lipid) in hydrogenated soya
      phosphatidylcholine/cholesterol/charged lipid [dicetyl phosphate (-) or
      stearylamine (+)] liposomes at molar ratios of 1:1:0, 7:2:0, 7:2:1(-) and
      7:2:1(+). The AmB contents in liposomes were determined by HPLC with UV detection
      at 382 nm. Stabilities of AmB in liposome formulations were compared with those
      in solution and powder forms, during storage at 4, 30 and 45 degrees C for 90
      days. Absorption studies of AmB across the rat skin were conducted, using
      vertical Franz diffusion cells at 37 degrees C for 24 h. The slowest degradation
      was observed in the positive liposome (7:2:1(+)AmB), with shelf life of
      approximately 1 year (30 degrees C). In comparison, the shelf lives of AmB in
      solution and powder were 4 and 14 days, respectively. AmB in positive liposomes
      seemed to demonstrate the highest flux in stratum corneum (58 ng/cm(2)/h), while
      the highest flux in viable epidermis (23 ng/cm(2)/h) was observed in negative
      liposomes. AmB entrapped in charged liposomes showed sustained skin absorption.
      The positively charged liposome might be the best formulation for AmB, due to its
      higher stability than other formulations.

PMID- 14726143
TI  - Isotropic medium chain mono-diglyceride/oil/water formulations for solubilization
      of lipophilic and hydrophilic drugs.
AB  - The aim of the study was to investigate isotropic mono- and diglyceride
      (MCMDG)/oil/water systems as vehicles for combinations of hydrophilic and
      lipophilic drugs. For two-component systems, MCMDG was mixed with various masses
      of water. For MCMDG/oily vehicles/water systems, mixtures were prepared by mixing
      oil and MCMDG prior to the addition of the appropriate masses of water. The
      isotropic region was examined by visual inspection and confirmed using polarized
      light microscopy. Viscosities of the systems were determined. Solubilities of
      hydrophilic (levamisole HCl) and lipopohilic (abamectin) drugs were determined in
      the isotropic formulations by HPLC analysis. The isotropic regions in the two
      component and three-component systems had water contents of up to 18% at 25
      degrees C. The isotropic formulations exhibited Newtonion flow. The viscosity of
      formulations having the same percentage of water increased with increasing ratio
      of MCMDG to oil in three-component systems. The solubilities of the levamisole
      HCl and abamectin were higher in the isotropic MCMDG/sesame oil/water
      formulations than in equivalent MCMDG/water formulations. In some formulations,
      the solubility of levamisole HCl was higher in the absence of abamectin than in
      combination with abamectin. Isotropic MCMDG/oil/water systems were obtained
      without the use of co-surfactants. Increasing water content in the system did not
      proportionally increase the solubility of hydrophilic drug. Solubilization of
      hydrophilic drug was affected by lipophilic drug in the presence or absence of SO
      and lipophilic drug solubility was affected by hydrophilic drug in the absence of
      SO. These systems are suitable vehicles to deliver both hydrophilic and
      lipophilic drugs and could be of interest for pharmaceutical formulations.

PMID- 14726144
TI  - Alternative sugars as potential carriers for dry powder inhalations.
AB  - Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a
      carrier in the drug powder blends. However, lactose cannot be used for compounds
      that interact with the reducing sugar function of the lactose, such as
      formoterol, budesonide or peptides and proteins. In this study, alternative
      carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore
      been evaluated for their potential use in DPI formulations. Raw materials were
      characterised physico-chemically and blends with the model drug substance
      budesonide were tested with respect to the aerosolization behaviour of the
      powders. It was found out that similarly to the problems known for lactose
      monohydrate, such as supplier variability, variability between different
      qualities of one supplier, the same difficulties apply to the alternative
      carriers investigated. Different sources and qualities of mannitol led to
      significant differences in the fine particle fraction (FPF), varying from 15 to
      50% for two different qualities of mannitol. Similar observations were made for
      the other carrier materials studied. Also, the influence of conditioning the raw
      material at different relative humidity was found to have substantial influence
      on the performance of drug/carrier blends which is characterised by a strong
      decrease in the FPF. In summary, mannitol showed potential as a drug carrier to
      be used in DPIs whereas the more hygroscopic sugars only showed poor
      dispersibility.

PMID- 14726146
TI  - An assessment of relative transcriptional availability from nonviral vectors.
AB  - To design better delivery systems that enhance transfection efficiency of
      nonviral vectors, we need to improve our understanding of the mechanisms
      governing both the amounts of plasmid delivered to the nucleus and gene
      expression. What is needed is a measure of transcriptional availability (TA): the
      average level of gene expression per plasmid delivered to the nucleus over the
      course of an experiment. We describe a method to measure TA and demonstrate its
      application. The chloramphenicol acetyltransferase reporter gene was transfected
      into NIH/3T3 cells using either cationic liposomes (TFL-3; O,O'-ditetradecanoyl-N
      (alpha-trimethylammonioacetyl) diethanolamine chloride (DC-6-14),
      dioleoylphosphatidylethanolamine (DOPE) and cholesterol, molar ratio 1/0.75/0.75)
      or cationic polymer (PEI; polyethylenimine). The time courses of both nuclear
      delivery of plasmids and reporter gene expression were measured for 4 h
      thereafter. For the conditions used, time courses of gene expression and plasmid
      nuclear delivery for the two vectors were different. To understand the origins of
      those differences, we applied a simple pharmacokinetic model, used the data to
      estimate the values of the model parameters, and interpret differences in
      estimated parameter values. The rate constant of delivery of plasmids into the
      nucleus for the TFL-3 vector was twice that of the PEI vector, whereas rate
      constant of elimination of plasmids in the nucleus for the PEI vector was four
      times that for the TFL-3 vector. The gene expression rate constant for the TFL-3
      vector was estimated to be seven times larger than that of the PEI vector for the
      conditions used. The pharmacokinetically determined average exposure of a nucleus
      to plasmid was about 17 times larger for the TFL-3 vector, relative to the PEI
      vector. That greater exposure resulted in increased relative gene expression.
      Overall, the TA from the TFL-3 vector was about 13 times greater than from the
      PEI vector. The experimental design combined with the adoption of pharmacokinetic
      concepts and principles provide a method to measure TA along with detailed
      insights into the mechanisms governing gene delivery and expression.

PMID- 14726145
TI  - Gamma scintigraphic evaluation of film-coated tablets intended for colonic or
      biphasic release.
AB  - The gastrointestinal transit and in vivo drug release behaviour of a film-coated
      tablet formulation was investigated in five healthy human subjects using the
      technique of gamma scintigraphy. The film coating system consisted of a mixture
      of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a
      coat weight gain of 9%. The estimated mean values of the gastric emptying time
      (62+/-17 min), small intestinal transit time (219+/-53 min), ileocaecal junction
      lag time (79+/-30 min) and the colon arrival time (345+/-33 min), were similar to
      published values for the transit of similar sized tablets in humans. The amount
      of radioactive tracer released from the labelled tablets was minimal when the
      tablets were in the stomach and the small intestine. There was increased release
      of radioactivity when the tablets were in the colon due to increased degradation
      of the film coatings by pectinolytic enzymes resident in the colon. The
      pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.

PMID- 14726148
TI  - Characterization of a zebrafish estrogen-sulfating cytosolic sulfotransferase:
      inhibitory effects and mechanism of action of phytoestrogens.
AB  - Cytosolic sulfotransferases (STs) are generally thought to be involved in
      detoxification of xenobiotics, as well as homeostasis of endogenous compounds
      such as thyroid/steroid hormones and catecholamine hormones/neurotransmitters. We
      report here the identification and characterization of a zebrafish estrogen
      sulfating cytosolic ST. The zebrafish ST was bacterially expressed, purified, and
      examined for enzymatic activities using a variety of endogenous compounds as
      substrates. Results showed that the enzyme displayed much higher activities
      toward two endogenous estrogens, estrone (E(1)) and 17beta-estradiol (E(2)), in
      comparison with thyroid hormones, 3,3',5-triiodothyronine (T(3)) and thyroxine
      (T(4)), dopamine, dihydroxyphenylalanine (Dopa), and dehydroepiandrosterone
      (DHEA). The kinetic parameters, K(m), and V(max), with estrogens and thyroid
      hormones as substrates were determined. The calculated V(max)/K(m) for E(1),
      E(2), T(3), and T(4) were, respectively, 31.6, 16.7, 1.5, and 0.8 nmol min(-1)
      mg(-1) microM(-1), indicating clearly the estrogens being preferred physiological
      substrates for the enzyme. The inhibitory effects of isoflavone phytoestrogens on
      the sulfation of E(2) by this zebrafish ST were examined. The IC(50) determined
      for quercetin, genistein, and daidzein were 0.7, 2.5, and 8 microM, respectively.
      Kinetic analyses revealed that the mechanism underlying the inhibition by these
      isoflavones to be of the competitive type.

PMID- 14726149
TI  - Effects of colchicine on liver functions of cirrhotic rats: beneficial effects
      result from stellate cell inactivation and inhibition of TGF beta1 expression.
AB  - Liver cirrhosis (LC) is a chronic disease with high mortality rate and its
      pathophysiology includes hepatic parenchymal cell destruction, connective tissue
      formation, and nodular regeneration. Colchicine has been used in liver diseases
      as an anti-inflammatory and anti-fibrotic drug. However, there is controversy
      over the beneficial effects of colchicine in LC treatment. In the present study,
      we injected rats with multiple doses of dimethylnitrosamine for 4 weeks and used
      rats with severe LC to determine whether colchicine treatment improved liver
      functions and resolved cirrhotic nodules. Colchicine (30-150microg/kg per day,
      i.p., for 4 weeks) failed to significantly increase the survival rate of LC rats.
      Animals were subjected to blood biochemical, liver histopathological and
      immunochemical analyses. The plasma albumin level, decreased in cirrhotic rats,
      was restored by colchicine treatment along with reduction of ascites. Colchicine
      decreased the accumulated extracellular matrix and the multiple fibrotic nodules
      formed in cirrhotic liver, and eliminated alpha-smooth muscle actin (alpha-SMA)
      positive cells. In activated stellate cells, colchicine inhibited alpha-SMA and
      transforming growth factor-beta1 (TGFbeta1) expression. The results of the
      present study showed that colchicine resolves cirrhotic nodules and accumulated
      fibers in the liver of LC rats, but failed to significantly improve the survival
      rate of LC animals, and that the beneficial effects of colchicine in cirrhotic
      animals result from stellate cell inactivation and inhibition of TGFbeta1
      expression.

PMID- 14726150
TI  - Detailed analytical subcellular fractionation of non-pregnant porcine corpus
      luteum reveals peroxisomes of normal size and significant UDP
      glucuronosyltransferase activity in the high-speed supernatant.
AB  - A detailed subfractionation of the non-pregnant porcine corpus luteum (CL) was
      performed employing differential centrifugation. Marker enzyme assays (i.e.,
      lactate dehydrogenase for the cytosol, NADPH-cytochrome P450 reductase for the
      endoplasmatic reticulum, catalase (CAT) for peroxisomes, glutamate dehydrogenase
      for the mitochondrial matrix and acid phosphatase for lysosomes) in all
      subfractions obtained exhibited a pattern of distribution similar to that
      observed with rat liver. These subfractions should be useful in connection with
      many types of future studies. In disagreement with previous biochemical and
      morphological studies, peroxisomes (identified on the basis of catalase activity
      and by Western blotting of catalase and of the major peroxisomal membrane protein
      (PMP-70)) sedimented together with mitochondria (i.e., at 5000 x g(av) for 10
      min) and not in the post-mitochondrial fraction prepared at 30,000 x g(av) for 20
      min by Peterson and Stevensson. No other classical peroxisomal enzymes were
      detectable in the porcine ovary, raising questions concerning the function of
      peroxisomes in this organ. Furthermore, UDP-glucuronosyltransferase (UGT),
      generally considered to be an integral membrane protein anchored in the
      endoplasmatic reticulum, was recovered in both the cytosolic (i.e., the
      supernatant after centrifugation at 50,000 x g(av) for 1h) and the microsomal
      fraction of the porcine corpus luteum, even upon further centrifugation of the
      former. In contrast, UGT sediments exclusively in the microsomal fraction upon
      subfractionation of the liver and ovary from rat.

PMID- 14726152
TI  - Naproxen affects Ca(2+) fluxes in mitochondria, microsomes and plasma membrane
      vesicles.
AB  - There is substantial evidence that nonsteroidal anti-inflammatory drugs (NSAIDs)
      affect cellular processes regulated by Ca(2+) ions, including the metabolic
      responses of the liver to Ca(2+)-dependent hormones. The aim of the present study
      was to determine whether the effects of naproxen are mediated by a direct action
      on cellular Ca(2+) fluxes. The effects of naproxen on 45Ca(2+) fluxes in
      mitochondria, microsomes and inside-out plasma membrane vesicles were examined.
      Naproxen strongly impaired the mitochondrial capacity to retain 45Ca(2+) and
      inhibited also ATP-dependent 45Ca(2+) uptake by microsomes. Naproxen did not
      modify 45Ca(2+) uptake by inside-out plasma membrane vesicles, but it inhibited
      the hexokinase/glucose-induced Ca(2+) efflux from preloaded vesicles. Additional
      assays performed in isolated mitochondria revealed that naproxen causes
      mitochondrial uncoupling and swelling in the presence of Ca(2+) ions. These
      effects were prevented by EGTA, ruthenium red and cyclosporin A, indicating that
      naproxen acts synergistically with Ca(2+) ions by promoting the mitochondrial
      permeability transition. The experimental results suggest that naproxen may
      impair the metabolic responses to Ca(2+)-dependent hormones acting by at least
      two mechanisms: (1) by interfering with the supply of external Ca(2+) through a
      direct action on the plasma membrane Ca(2+) influx, and (2) by affecting the
      refilling of the agonist-sensitive internal stores, including endoplasmic
      reticulum and mitochondria.

PMID- 14726151
TI  - Sanguinarine is a potent inhibitor of oxidative burst in DMSO-differentiated HL
      60 cells by a non-redox mechanism.
AB  - Sanguinarine (SA), a member of the benzo[c]phenanthridine isoquinoline alkaloids,
      has been shown to possess antimicrobial, anti-inflammatory, and antioxidant
      properties. We examined the effects of SA on oxidative burst in DMSO
      differentiated HL-60 cells, an excellent model for studying oxidative burst. SA
      inhibited both N-formyl-Met-Leu-Phe (fMLP) and phorbol 12-myristate 13-acetate
      (PMA)-induced oxidative burst with half-maximal concentration for inhibition
      (IC(50)) of 1.5 and 1.8 microM, respectively. Despite suggestions of SA
      antioxidant activity this inhibition cannot be ascribed to radical scavenging
      property of SA because the IC(50) for superoxide dismutase-like activity in a non
      cellular system was 60 microM. TROLOX, a water-soluble vitamin E analog, had
      IC(50) of 3 microM in the same system. Moreover, cyclic voltammetry measurements
      show that SA is not an easily oxidizable species, with a peak anodic potential at
      700 mV, as compared to TROLOX with peak anodic potential at 200 mV. On the other
      hand, TROLOX, when used in cell suspension, was much poorer inhibitor of
      oxidative burst than SA. When testing direct effect of SA on NADPH oxidase in the
      post-granular fraction of disrupted cells, the IC(50) was found to be 8.3 microM.
      It is higher than that observed in whole cells, however, the shift may be
      ascribed to SDS effect on SA activity. We conclude the SA inhibition of oxidative
      burst is not caused by SA redox activity but most likely is a result of SA
      affecting the activity of NADPH oxidase directly and in part by preventing the
      formation of NADPH oxidase protein complex.

PMID- 14726153
TI  - Stress-mediated modulation of B(alpha)P-induced hepatic CYP1A1: role of
      catecholamines.
AB  - The present study investigated the involvement of catecholamines in stress
      mediated alterations in CYP1A1 induction by benzo(alpha)pyrene (B(alpha)P) in
      Wistar rats. This was achieved by measuring EROD activity and CYP1A1 mRNA levels
      in liver tissue from rats exposed to restraint stress and B(alpha)P coupled with
      pharmacological modulation of peripheral and central catecholamine levels and
      different adrenoceptors. In a state of reserpine-induced central and peripheral
      catecholamine depletion, stress strongly suppressed EROD induction. Peripheral
      catecholamines do not appear to play a critical role in the stress-mediated
      modulation of EROD inducibility by B(alpha)P. Stress did not alter EROD
      inducibility by B(alpha)P when peripheral catecholamines were either depleted by
      guanethidine or supplemented by peripheral adrenaline administration. On the
      other hand, central noradrenergic systems appear to have a role in the stress
      mediated changes in B(alpha)P-induced EROD activity and Cyp1A1 gene expression.
      Stimulation or blockade of noradrenaline release with atipamezole and
      dexmedetomidine, respectively, significantly modified the up-regulating effect of
      stress. Alpha1 adrenoceptors also appear to participate in the effect of stress
      on EROD inducibility. Alpha1-blockade with prazosin potentiated the up-regulating
      effect of stress, possibly preventing the down-regulating effect of
      noradrenaline. Beta adrenoceptors also seem to be involved directly or indirectly
      in the stress-mediated modulation of Cyp1A1, as propranolol (beta-antagonist)
      blocked the down-regulating effect of stress on B(alpha)P-induced Cyp1A1 gene
      expression. Plasma corticosterone alterations after stress were not related to
      alterations in the B(alpha)P-induced EROD activity and Cyp1A1 gene expression. In
      conclusion, stress appears to interfere in the regulation of B(alpha)P-induced
      hepatic CYP1A1 in an unpredictable manner and via signalling pathways not always
      directly related to catecholamines. In particular, whenever drug treatment
      disrupts noradrenergic neurotransmission, other stress-stimulated factors appear
      to modify the induction of CYP1A1. In summary, regulation of induction of hepatic
      CYP1A1 during stress appears to involve various components of the stress system,
      including central and peripheral catecholamines, which interact in a complex
      manner, yet to be elucidated.

PMID- 14726154
TI  - A sesquiterpene lactone, costunolide, interacts with microtubule protein and
      inhibits the growth of MCF-7 cells.
AB  - Costunolide is an active sesquiterpene lactone of medicinal herbs with anti
      inflammatory and potential anti-cancer activity. Nevertheless, the
      pharmacological pathways of costunolide have not yet been fully elucidated. In
      this study we showed that costunolide exerts a dose-dependent antiproliferative
      activity in the human breast cancer MCF-7 cells. In addition, light microscopy
      observations indicated that costunolide affected nuclear organization and
      reorganized microtubule architecture. The antiproliferative and antimicrotubular
      effects of costunolide were not influenced by paclitaxel, well-known microtubule
      stabilizing anticancer agent. The microtubule-interacting activity of costunolide
      was confirmed by in vitro studies on purified microtubular protein. In fact,
      costunolide demonstrated polymerizing ability, by inducing the formation of well
      organized microtubule polymers. Our data suggest an interaction of costunolide
      with microtubules, which may represent a new intracellular target for this drug.

PMID- 14726155
TI  - Cigarette smoke extract increases S-adenosylmethionine and cystathionine in human
      lung epithelial-like (A549) cells.
AB  - The effect of cigarette smoke extract (CSE) on S-adenosylmethionine (SAM), S
      adenosylhomocysteine (SAH), and sulfur amino acid metabolism was examined in
      human lung epithelial-like (A549) cells exposed to various CSE concentrations
      (2.5-100%) for 24 or 48 h. Intracellular SAM and SAM/SAH ratio were elevated
      after exposure to CSE for 48 h. Cell SAH content decreased, but the effect was
      not consistent. Cellular cystathionine, cysteine, and methionine levels were
      increased after CSE exposure for 48h. Sub-acute exposure to CSE induced increases
      in cellular SAM and SAM/SAH ratio. The transsulfuration pathway was likely
      activated by CSE since cystathionine increased, potentially contributing to the
      increased total intracellular GSH content.

PMID- 14726156
TI  - Studies on the DT-diaphorase-catalysed reaction employing quinones as substrates:
      evidence for a covalent modification of DT-diaphorase by tetrachloro-p
      benzoquinone.
AB  - In this study, the kinetic parameters, V(max) and K(m), of rat liver DT
      diaphorase were determined for a series of p-benzoquinones, with methyl, methoxy,
      cyano, hydroxy and halo substituents. The results show that there is no
      correlation between the experimentally determined rates of p-benzoquinone
      reduction by DT-diaphorase and the calculated chemical reactivity of the examined
      substrates as expressed by the energy of the lowest unoccupied molecular orbital,
      E(LUMO). However, a reasonable correlation was found between the natural
      logarithm of V(max)/K(m) and the partition coefficient of the p-benzoquinones
      (r=0.81). Furthermore, tetrachloro-p-benzoquinone, one of the tested quinones is
      shown to be an inhibitor of rat DT-diaphorase. The presence of bovine serum
      albumin (BSA) in the incubation mixture protects DT-diaphorase against the
      inactivation by tetrachloro-p-benzoquinone, probably by interacting with the
      quinone. Maldi-Tof analysis of the incubation mixture of the purified DT
      diaphorase and tetrachloro-p-benzoquinone showed that every subunit of the enzyme
      shifted about +414 amu, whereas the dimer shifted about +849 amu relative to
      control values. This indicates a covalent modification of the rat liver DT
      diaphorase by tetrachloro-p-benzoquinone.

PMID- 14726157
TI  - Poliomyelitis-eradication initiative's wider lessons.

PMID- 14726158
TI  - Childhood stunting: measuring and stemming the staggering costs of inadequate
      water and sanitation.

PMID- 14726159
TI  - Air pollution, oxidative stress, and allergic response.

PMID- 14726160
TI  - Coagulation, inflammation, and pregnancy complications.

PMID- 14726161
TI  - The Surgeon General's report on smoking and health 40 years later: still
      wandering in the desert.

PMID- 14726162
TI  - Molecular epidemiology of the novel coronavirus that causes severe acute
      respiratory syndrome.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly emerged disease
      caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003,
      affecting over 30 countries. We have used molecular epidemiology to define the
      patterns of spread of the virus in Hong Kong and beyond. METHODS: The case
      definition of SARS was based on that recommended by WHO. We genetically sequenced
      the gene for the S1 unit of the viral spike protein of viruses from patients with
      SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We
      undertook phylogenetic comparisons with 27 other sequences available from public
      databases (Genbank). FINDINGS: Most of the Hong Kong viruses (139/142), including
      those from a large outbreak in an apartment block, clustered closely together
      with the isolate from a single index case (HKU-33) who came from Guangdong to
      Hong Kong in late February. Three other isolates were genetically distinct from
      HKU-33 in Hong Kong during February, but none of these contributed substantially
      to the subsequent local outbreak. Viruses identified in Guangdong and Beijing
      were genetically more diverse. INTERPRETATION: The molecular epidemiological
      evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as
      the viruses from Canada, Vietnam, and Singapore, are genetically closely linked.
      Three viruses found in Hong Kong in February were phylogenetically distinct from
      the major cluster, which suggests that several introductions of the virus had
      occurred, but that only one was associated with the subsequent outbreak in Hong
      Kong, which in turn spread globally.

PMID- 14726163
TI  - ZAP-70 expression and prognosis in chronic lymphocytic leukaemia.
AB  - BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease; many
      patients never need treatment, whereas some have poor outcomes. New treatments,
      which can induce complete remissions, allow patients with poor outlook to be
      treated while they are still asymptomatic. Whether or not the IgVH gene is
      mutated is the best predictor of clinical outcome, but this assay is unsuited to
      the routine laboratory. The gene coding for ZAP-70, a tyrosine kinase protein
      normally expressed in T and NK cells, has been shown by gene-expression profiling
      to be differentially expressed between patients with mutated and unmutated IgVH
      genes. We assessed whether ZAP-70 could be used as a prognostic marker in CLL.
      METHODS: We developed a flow cytometry assay for ZAP-70 protein expression and
      investigated its concordance with ZAP-70 mRNA expression, IgVH gene mutational
      status, and clinical outcome in 167 patients with CLL. FINDINGS: We showed high
      concordance between ZAP-70 protein expression and IgVH gene mutations. 108
      patients (65%) had mutated IgVH genes and were ZAP-70 negative; 46 (28%) had
      unmutated IgVH genes and were ZAP-70 positive. Findings were discordant in 13
      patients: six (4%) had mutated IgVH genes but were ZAP-70 positive, and seven
      (4%) had unmutated IgVH genes and were ZAP-70 negative. Expression of mRNA showed
      97% concordance with ZAP-70 protein. Median survival was 24.4 years (95% CI 15.1
      33.8) in ZAP-70 negative patients and 9.3 years (7.0-11.5) in those who were ZAP
      70 positive (hazard ratio 5.5, 2.8-.8). INTERPRETATION: ZAP-70 protein, which can
      be measured by flow cytometry in the general laboratory, is a reliable prognostic
      marker in CLL, equivalent to that of IgVH gene mutational status.

PMID- 14726164
TI  - Effect of water and sanitation on childhood health in a poor Peruvian peri-urban
      community.
AB  - BACKGROUND: Inadequate water and sanitation adversely affect the health of
      children in developing countries. We aimed to assess the effects of water and
      sanitation on childhood health in a birth cohort of Peruvian children. METHODS:
      We followed up children once a day for diarrhoea and once a month for
      anthropometry, and obtained data for household water and sanitation at baseline.
      FINDINGS: At 24 months of age, children with the worst conditions for water
      source, water storage, and sanitation were 1.0 cm (95% CI 0.1-0.8) shorter and
      had 54% (-1 to 240) more diarrhoeal episodes than did those with the best
      conditions. Children from households with small storage containers had 28% (1-63)
      more diarrhoeal episodes than did children from households with large containers.
      Lack of adequate sewage disposal explained a height deficit of 0.9 cm (0.2-1.7)
      at 24 months of age. Better water source alone did not accomplish full health
      benefits. In 24-month-old children from households with a water connection, those
      in households without adequate sewage disposal and with small storage containers
      were 1.8 cm (0.1-3.6) shorter than children in households with sewage and with
      large storage containers. INTERPRETATION: Our findings show that nutritional
      status is a useful endpoint for water and sanitation interventions and
      underscores the need to improve sanitation in developing countries. Improved and
      more reliable water sources should discourage water storage at risk of becoming
      contaminated, decrease diarrhoeal incidence, and improve linear growth in
      children.

PMID- 14726165
TI  - Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement
      of allergic responses: randomised, placebo-controlled crossover study.
AB  - BACKGROUND: Particulate pollution is associated with the occurrence of asthma and
      allergy. The model pollutant, diesel exhaust particles, can participate with
      allergens in starting and exacerbating allergic airway diseases in part by
      production of reactive oxygen species. Glutathione-S-transferases (GSTs) can
      metabolise reactive oxygen species and detoxify xenobiotics present in diesel
      exhaust particles. We tested the hypothesis that null genotypes for GSTM1 and
      GSTT1, and GSTP1 codon 105 variants (I105 and V105) are key regulators of the
      adjuvant effects of diesel exhaust particles on allergic responses. METHODS:
      Patients sensitive to the ragweed allergen were challenged intranasally with
      allergen alone and with allergen plus diesel exhaust particles in a randomised
      order at separate visits. Nasal allergen-specific IgE, histamine, interleukin 4,
      and interferon gamma concentrations were measured before and 24 h after
      challenge. FINDINGS: Individuals with GSTM1 null or the GSTP1 I105 wildtype
      genotypes showed enhanced nasal allergic responses in the presence of diesel
      exhaust particles. Compared with patients with a functional GSTM1 genotype, GSTM1
      null patients had a significantly larger increase in IgE (median 102.5 U/mL
      [range 1.0-510.5] vs 45.5 U/mL [1.5-60.6], p=0.03) and histamine (14.0 nmol/L [
      0.2-24.7] vs 7.4 nmol/L [1.2-12.3], p=0.02) after diesel exhaust particles plus
      allergen challenge. The I105 GSTP1 genotype was associated with an increase in
      IgE (120.3 U/mL [6.7-510.5] vs 27.7 U/mL [-1.5-60.6], p=0.03) and histamine (13.8
      nmol/L [3.1-24.7] vs 5.2 nmol/L [-0.2-19.6], p=0.01) after challenge with diesel
      exhaust particles and allergens. The diesel exhaust particles enhancement was
      largest in patients with both the GSTM1 null and GSTP1 I/I genotypes.
      INTERPRETATION: GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust
      particles on allergic inflammation.

PMID- 14726166
TI  - A prisoner with acute renal failure.

PMID- 14726167
TI  - Persistence of impaired pancreatic beta-cell function in children treated for
      acute lymphoblastic leukaemia.
AB  - Treatment for acute lymphoblastic leukaemia can induce alterations of glucose
      metabolism, but long-term follow-up data on this topic are still absent. We aimed
      to study glucose metabolism by intravenous and oral glucose tolerance testing in
      32 children affected by acute lymphoblastic leukaemia and who were off-therapy
      for at least 1 year. 22 (69%) children presented with impaired first-phase
      insulin response, which in nine children was associated with impaired glucose
      tolerance and in one child with overt diabetes. Fasting insulin (4.65 mU/L, 95%
      CI 1.1-8.1; p=0.008), insulinogenic index (0.46; 0.02-0.98; p=0.03), and
      homoeostatic model assessment beta-cell function (80.1, 7.2-153; p=0.02) were
      reduced in the children with impaired insulin response. Chemotherapy for acute
      lymphoblastic leukaemia is associated with beta-cell function damage, which
      persists even after therapy has been stopped.

PMID- 14726168
TI  - Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor
      of miscarriage.
AB  - Macrophage inhibitory cytokine 1 (MIC 1) is thought to have immunomodulatory
      actions favouring fetal viability. We measured serum concentrations of MIC 1 in
      asymptomatic women at 6-13 weeks' gestation who subsequently miscarried or who
      had already miscarried. MIC 1 concentrations in the miscarriage cohort (n=100),
      were a third of those who had ongoing pregnancies (n=197). Multiples of the
      median for miscarriage was 0.32 (95% CI 0.23-0.32) versus 1.00 (0.93-1.06) for
      ongoing pregnancies; p<0.0001. Concentrations were just as low 3 weeks before
      diagnosis as on the day of diagnosis. That MIC 1 serum concentrations seem to be
      low weeks before miscarriage suggests possible predictive and causative roles, as
      well as therapeutic potential.

PMID- 14726169
TI  - Infective endocarditis.
AB  - Despite improvements in health care, the incidence of infective endocarditis has
      not decreased over the past decades. This apparent paradox is explained by a
      progressive evolution in risk factors; while classic predisposing conditions such
      as rheumatic heart disease have been all but eradicated, new risk factors for
      infective endocarditis have emerged. These include intravenous drug use,
      sclerotic valve disease in elderly patients, use of prosthetic valves, and
      nosocomial disease. Newly identified pathogens, which are difficult to cultivate-
      eg, Bartonella spp and Tropheryma whipplei--are present in selected individuals,
      and resistant organisms are challenging conventional antimicrobial therapy.
      Keeping up with these changes depends on a comprehensive approach, allying
      understanding of the pathogenesis of disease with the development of new drugs
      for infective endocarditis. Infection by staphylococci and streptococci is being
      dissected at the molecular level. New ideas for antimicrobial agents are being
      developed. These novel insights should help redefine preventive and therapeutic
      strategies against infective endocarditis.

PMID- 14726170
TI  - Malaria vaccine developments.
AB  - Large gains in the reduction of malaria mortality in the early 20th century were
      lost in subsequent decades. Malaria now kills 2-3 million people yearly.
      Implementation of malaria control technologies such as insecticide-treated
      bednets and chemotherapy could reduce mortality substantially, but an effective
      malaria vaccine is also needed. Advances in vaccine technology and immunology are
      being used to develop malaria subunit vaccines. Novel approaches that might yield
      effective vaccines for other diseases are being evaluated first in malaria. We
      describe progress in malaria vaccine development in the past 5 years: reasons for
      cautious optimism, the type of vaccine that might realistically be expected, and
      how the process could be hastened. Although exact predictions are not possible,
      if sufficient funding were mobilised, a deployable, effective malaria vaccine is
      a realistic medium-term to long-term goal.

PMID- 14726171
TI  - Appropriate body-mass index for Asian populations and its implications for policy
      and intervention strategies.
AB  - A WHO expert consultation addressed the debate about interpretation of
      recommended body-mass index (BMI) cut-off points for determining overweight and
      obesity in Asian populations, and considered whether population-specific cut-off
      points for BMI are necessary. They reviewed scientific evidence that suggests
      that Asian populations have different associations between BMI, percentage of
      body fat, and health risks than do European populations. The consultation
      concluded that the proportion of Asian people with a high risk of type 2 diabetes
      and cardiovascular disease is substantial at BMIs lower than the existing WHO cut
      off point for overweight (> or =25 kg/m2). However, available data do not
      necessarily indicate a clear BMI cut-off point for all Asians for overweight or
      obesity. The cut-off point for observed risk varies from 22 kg/m2 to 25 kg/m2 in
      different Asian populations; for high risk it varies from 26 kg/m2 to 31 kg/m2.
      No attempt was made, therefore, to redefine cut-off points for each population
      separately. The consultation also agreed that the WHO BMI cut-off points should
      be retained as international classifications. The consultation identified further
      potential public health action points (23.0, 27.5, 32.5, and 37.5 kg/m2) along
      the continuum of BMI, and proposed methods by which countries could make
      decisions about the definitions of increased risk for their population.

PMID- 14726172
TI  - The Y-Y paradox.

PMID- 14726173
TI  - Dried blood spot technology for CD4+ T-cell counting.

PMID- 14726174
TI  - Dried blood spot technology for CD4+ T-cell counting.

PMID- 14726176
TI  - Spreading the word, but not too thinly.

PMID- 14726177
TI  - Neutralising antibodies against interferon beta in multiple sclerosis.

PMID- 14726178
TI  - Practical strategies to combat biopiracy.

PMID- 14726179
TI  - Neutralising antibodies against interferon beta in multiple sclerosis.

PMID- 14726180
TI  - Neutralising antibodies against interferon beta in multiple sclerosis.

PMID- 14726182
TI  - Health of thalidomide victims and their progeny.

PMID- 14726183
TI  - Marketing ALLHAT.

PMID- 14726184
TI  - Artificial neural networks in predicting outcome of gastrointestinal haemorrhage.

PMID- 14726185
TI  - Artificial neural networks in predicting outcome of gastrointestinal haemorrhage.

PMID- 14726187
TI  - Doctor performance and public accountability.

PMID- 14726188
TI  - International register of trial acronyms.

PMID- 14726189
TI  - Expiry-date tampering.

PMID- 14726190
TI  - Expiry-date tampering.

PMID- 14726191
TI  - Where now for problem based learning?

PMID- 14726197
TI  - Support.

PMID- 14726198
TI  - The gender gap.

PMID- 14726199
TI  - Antimicrobial peptides from ranid frogs: taxonomic and phylogenetic markers and a
      potential source of new therapeutic agents.
AB  - Granular glands in the skins of frogs of the genus Rana, a widely distributed
      group with over 250 species, synthesize and secrete a remarkably diverse array of
      peptides with antimicrobial activity that are believed to have arisen as a result
      of multiple gene duplication events. Almost without exception, these components
      are hydrophobic, cationic and form an amphipathic alpha-helix in a membrane
      mimetic solvent. The peptides can be grouped into families on the basis of
      structural similarity. To date, brevinin-1, esculentin-1, esculentin-2, and
      temporin peptides have been found in ranid frogs of both Eurasian and North
      American origin; ranalexin, ranatuerin-1, ranatuerin-2 and palustrin peptides
      only in N. American frogs; and brevinin-2, tigerinin, japonicin, nigrocin and
      melittin-related peptides only in Eurasian frogs. It is generally assumed that
      this structurally diversity serves to protect the organism against a wide range
      of pathogens but convincing evidence in support of this hypothesis is still
      required. The possibility that "antimicrobial peptides" fulfill additional or
      alternative biological functions should not be rejected. The molecular
      heterogeneity of the peptide families, particularly brevinin-1, brevinin-2 and
      ranatuerin-2, may be exploited for the purposes of unequivocal identification of
      specimens and for an understanding of phylogenetic interrelationships between
      species. The broad-spectrum antibacterial and antifungal activities of certain
      peptides, for example esculentin-1, ranalexin-1 and ranatuerin, together with
      their relatively low hemolytic activity, make them candidates for development
      into therapeutically useful anti-infective agents.

PMID- 14726201
TI  - L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently
      binding to the essential 135Cys of the enzyme.
AB  - Aspartate-beta-semialdehyde dehydrogenase (ASADH) from Escherichia coli is
      inhibited by L- and D-cystine, and by other cystine derivatives. Enzyme
      inhibition is quantitatively reversed by addition of dithiothreitol (DTT),
      dithioerythrytol, beta-mercaptoethanol, di-mercaptopropanol or glutathione to the
      cystine-inactivated enzyme. Cystine labeling of the enzyme is a pH dependent
      process and is optimal at pH values ranging from 7.0 to 7.5. Both the cysteine
      incorporation profile and the inactivation curve of the enzyme as a function of
      pH suggest that a group(s) with pK(a) of 8.5 could be involved in cystine
      binding. Stoichiometry of the inactivation reaction indicates that one cysteine
      residue from the enzyme subunit is reactive against cystine, as found by direct
      incorporation of radioactive cystine into the enzyme and by free-thiol titration
      of the enzyme with 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) before and after the
      cystine treatment. One mole of cysteine is released from each mol of cystine
      after reaction with the enzyme. ASA, NADP and NADPH did not prevent cystine
      inhibition. The [35S]cysteine-labelled enzyme can be visualized after
      electrophoresis in polyacrylamide gels and further detection by autoradiography.
      After pepsin treatment of the [35S]cysteine-inactivated enzyme, a main
      radioactive peptide was isolated by HPLC. The amino acid sequence of this peptide
      was determined as FVGGN(Cys)(2)TVSL, thus demonstrating that the essential 135Cys
      is the amino acid residue modified by the treatment with cystine.

PMID- 14726200
TI  - Effects of ligand binding and conformational switching on intracellular stability
      of human thymidylate synthase.
AB  - Thymidylate synthase (TS) is the target in colon cancer therapeutic protocols
      utilizing such drugs as 5-fluorouracil and raltitrexed. The effectiveness of
      these treatments is hampered by emerging drug resistance, usually related to
      increased levels of TS. Human TS (hTS) is unique among thymidylate synthases from
      all species examined as its loop 181-197 can assume two main conformations
      related by rotation of 180 degrees. In one conformation, "active", the catalytic
      Cys-195 is positioned in the active site; in the other conformation, "inactive",
      it is at the subunit interface. Also, in the active conformation, region 107-128
      has one well-defined conformation while in the inactive conformation this region
      assumes multiple conformations and is disordered in crystals. The native protein
      exists in apparent equilibrium between the two conformational states, while the
      enzyme liganded with TS inhibitors assumes the active conformation. The native
      protein has been reported to bind to several mRNAs, including its own mRNA, but
      upon ligation, RNA binding activity is lost. Ligation of TS by inhibitors also
      stabilizes it to turnover. Since currently used TS-directed drugs stabilize the
      active conformation and slow down the enzyme degradation, it is postulated that
      inhibitors of hTS stabilizing the inactive conformation of hTS should cause a
      down-regulation in enzyme levels as well as inactivate the enzyme.

PMID- 14726202
TI  - Crystal structure of adenine phosphoribosyltransferase from Leishmania
      tarentolae: potential implications for APRT catalytic mechanism.
AB  - The three-dimensional structure of Leishmania tarentolae adenine
      phosphoribosyltransferase (APRT) in complex with adenosine-5-monophosphate (AMP)
      and a phosphate ion has been solved. Refinement against X-ray diffraction data
      extending to 2.2-A resolution led to a final crystallographic R factor of 18.3%.
      Structural comparisons amongst this APRT enzyme and other 'type I' PRTases whose
      structures have been determined reveal several important features of the PRTases
      catalytic mechanism. Based on structural superpositions and molecular interaction
      potential calculations, it was possible to suggest that the PRPP is the first
      substrate to bind, while the AMP is the last product to leave the active site, in
      accordance to recent kinetic studies performed with the Leishmania donovani APRT.

PMID- 14726203
TI  - Ostrich (Struthio camelus) eggshell matrix contains two different C-type lectin
      like proteins. Isolation, amino acid sequence, and posttranslational
      modifications.
AB  - In contrast to chicken and goose, the ostrich calcified eggshell layer matrix
      contained two different C-type lectin-like proteins as major components. These
      proteins, named struthiocalcin-1 (SCA-1) and struthiocalcin-2 (SCA-2), were
      isolated and their amino acid sequence was determined. SCA-1 clearly was the
      ortholog of goose eggshell ansocalcin. Its amino acid sequence had the same
      length as that of ansocalcin (132 aa) and showed 65% sequence identity with the
      goose eggshell protein compared to 41% with chicken eggshell ovocleidin-17.
      Furthermore, as ansocalcin and unlike ovocleidin-17, it contained an additional,
      seventh, cysteine that was, however, located close to the C-terminus of SCA-1 and
      not in the N-terminal third of the sequence as in ansocalcin. SCA-2 showed
      features of both ansocalcin and chicken eggshell ovocleidin-17 (OC-17). Its
      sequence was 46% identical to that of ansocalcin and 36% identical to OC-17. It
      contained the same stretches of negatively charged amino acids conserved in
      ansocalcin and SCA-1, which are absent in OC-17. On the other hand, its length of
      142 amino acids was identical to that of OC-17 and it contained only the usual
      set of six cysteines conserved in most C-type lectin-like proteins. The presence
      of three phosphorylated serines located at exactly the same region of the
      sequence as the two phosphoserines of OC-17 further stressed the similarity
      between SCA-2 and OC-17.

PMID- 14726204
TI  - Simultaneous analysis of esterase and transferase activities in cytosol proteins
      from the bovine retina by using microscale non-denaturing two-dimensional
      electrophoresis.
AB  - Esterase and transferase activities were analyzed simultaneously after cytosol
      proteins in the bovine retina were separated by microscale non-denaturing two
      dimensional electrophoresis (2-DE). Esterase activity was specifically inhibited
      by an esterase inhibitor, 9-amino-1,2,3,4-tetra hydroacridine (tacrine), and
      transferase activity was specifically inhibited by a glutathione S-transferase
      (GST) inhibitor, 2-phenyl-1,2-benziso selenazol-3(2H)-one (ebselen). Both
      esterase and transferase were precipitated when ammonium sulfate was added to the
      cytosol up to 50% saturation (50% AS fraction), and were detected in the 50% AS
      fraction by using the 2-DE. After the cytosol proteins in the 50% AS fraction
      were separated by using non-denaturing 2-DE, polypeptides of the separated
      proteins were identified by peptide mass fingerprinting and post-source decay
      analysis by using MALDI-MS, or by immunoreactivity by using a specific antibody.
      The spots of esterase and transferase activities in the 2-DE pattern were
      identified as phosphodiesterase and GST, respectively. This simultaneous analysis
      of enzyme activities can be applied to screen-specific or non-specific medicines
      which affect enzyme activities.

PMID- 14726205
TI  - Cold-active esterase from Psychrobacter sp. Ant300: gene cloning,
      characterization, and the effects of Gly-->Pro substitution near the active site
      on its catalytic activity and stability.
AB  - The gene encoding an esterase (PsyEst) of Psychrobacter sp. Ant300, a
      psychrophilic bacterium isolated from Antarctic soil, was cloned, sequenced, and
      expressed in Escherichia coli. PsyEst, which is a member of hormone-sensitive
      lipase (HSL) group of the lipase/esterase family, is a cold-active, themolabile
      enzyme with high catalytic activity at low temperatures (5-25 degrees C), low
      activation energy (e.g., 4.6 kcal/mol for hydrolysis of p-nitrophenyl butyrate),
      and a t(1/2) value of 16 min for thermal inactivation during incubation at 40
      degrees C and pH 7.9. A three-dimensional structural model of PsyEst predicted
      that Gly(244) was located in the loop near the active site of PsyEst and that
      substitution of this amino-acid residue by proline should potentially rigidify
      the active-site environment of the enzyme. Thus, we introduced the Gly(244)-->Pro
      substitution into the enzyme. Stability studies showed that the t(1/2) value for
      thermal inactivation of the mutant during incubation at 40 degrees C and pH 7.9
      was 11.6 h, which was significantly greater than that of the wild-type enzyme.
      The k(cat)/K(m) value of the mutant was lower for all substrates examined than
      the value of the wild type. Moreover, this amino-acid substitution caused a shift
      of the acyl-chain length specificity of the enzyme toward higher preference for
      short-chain fatty acid esters. All of these observations could be explained in
      terms of a decrease in active-site flexibility brought about by the mutation and
      were consistent with the hypothesis that cold activity and thermolability arise
      from local flexibility around the active site of the enzyme.

PMID- 14726206
TI  - Lattice stabilization and enhanced diffraction in human p38 alpha crystals by
      protein engineering.
AB  - Mitogen-activated protein (MAP) kinase p38 alpha is activated in response to
      environmental stress and cytokines, and plays a significant role in inflammatory
      responses. For these reasons, it is an important target for the treatment of a
      wide range of inflammatory and autoimmune diseases. The crystals of p38 alpha
      that we obtained by published procedures were usually small, quite mosaic, and
      difficult to reproduce and thus posed a difficulty for the intensive high
      resolution studies required for a structure-guided drug discovery approach. Based
      on crystallographic and biochemical evidences, we prepared a single point
      mutation of a surface cysteine (C162S) and found that it prevents aggregation and
      improves the homogeneity and stability of the enzyme. This mutation also
      facilitates the crystallization process and increases the diffracting power of
      p38 alpha crystals. Surprisingly, we found that the mutation induces a change in
      the conformation of a nearby surface loop resulting in stronger lattice
      interactions, consistent with the improved crystal quality. The mutant protein,
      because of its improved stability and strengthened lattice interactions, thus
      provides a significantly improved reagent for use in structure-based drug design
      for this important disease target.

PMID- 14726207
TI  - A mutant phospholipase D with enhanced thermostability from Streptomyces sp.
AB  - To investigate the contribution of amino acid residues to the thermostability of
      phospholipase D (PLD), a chimeric form of two Streptomyces PLDs (thermolabile
      K1PLD and thermostable TH-2PLD) was constructed. K/T/KPLD, in which residues 329
      441 of K1PLD were recombined with the homologous region of TH-2PLD, showed a
      thermostability midway between those of K1PLD and TH-2PLD. By comparing the
      primary structures of Streptomyces PLDs, the seven candidates of thermostability
      related amino acid residues of K1PLD were identified. The K1E346DPLD mutant, in
      which Glu346 of K1PLD was substituted with Asp by site-directed mutagenesis,
      exhibited enhanced thermostability, which was almost the same as that of TH-2PLD.

PMID- 14726208
TI  - ATPase activity of non-ribosomal peptide synthetases.
AB  - Adenylation domains of non-ribosomal peptide synthetases (NRPS) catalyse the
      formation of aminoacyl adenylates, and in addition synthesize mono- and
      dinucleoside polyphosphates. Here, we show that NRPS systems furthermore contain
      an ATPase activity in the range of up to 2 P(i)/min. The hydrolysis rate by apo
      tyrocidine synthetase 1 (apo-TY1) is enhanced in the presence of non-cognate
      amino acid substrates, correlating well with their structural features and the
      diminishing adenylation efficiency. A comparative analysis of the functional
      relevance of an analogous sequence motif in P-type ATPases and adenylate kinases
      (AK) allowed a putative assignment of the invariant aspartate residue from the
      TGDLA(V)R(K) core sequence in NRPS as the Mg(2+) binding site. Less pronounced
      variations in ATPase activity are observed in domains with relaxed amino acid
      specificity of gramicidin S synthetase 2 (GS2) and delta-(L-aminoadipyl)-L
      cysteinyl-D-valine synthetase (ACVS), known to produce a set of substitutional
      variants of the respective peptide product. These results disclose new
      perspectives about the mode of substrate selection by NRPS.

PMID- 14726209
TI  - Domain exchange between isoforms of ferredoxin-NADP+ reductase produces a
      functional enzyme.
AB  - Two isoforms of ferredoxin-NADP(+) reductase (FNR) exist in higher plants, the
      leaf (or photosynthetic) and the root (or non-photosynthetic) isoform, which have
      48% amino acid sequence identity and display specific structural and functional
      features. With the aim to gain further insight into the structure-function
      relationship of this enzyme, we designed two novel chimeric flavoenzymes by
      swapping the structural domains between the leaf and the root isoforms.
      Characterization of the chimeras would allow dissection of the contribution of
      the individual domains to catalysis. The chimera obtained by grafting together
      the FAD-binding domain of the root-isoform and the NADP-binding domain of the
      leaf-isoform was inactive when expressed in Escherichia coli. On the other hand,
      the chimera assembled in the opposite way (leaf FAD-binding domain and root NADP
      binding domain) was functional and was produced in the bacterial host to a level
      threefold higher than that of the parent enzymes. The protein was purified and
      found to be as stable as the natural isoforms. Limited proteolysis excluded the
      presence in the chimera of misfolded regions. The affinity of the chimera for
      ferredoxin I (Fd I) was similar to that of the leaf isoform, although
      interprotein electron-transfer was partially impaired. As occurs with the root
      isoform, the chimera bound NADP(+) with high affinity, while spectroscopic
      evidence suggested that the conformation adopted by the nicotinamide moiety bound
      to the chimera was similar to that observed in the leaf enzyme. Interestingly,
      the chimera, by combining favorable features from both parent isoforms, acquired
      a catalytic efficiency (k(cat)/K(m)), as an NADPH-dependent diaphorase, higher
      than those of both the root ( approximately 2-fold) and the leaf enzyme (
      approximately 5-fold). Thus, molecular breeding between isozymes has improved the
      catalytic properties of FNR.

PMID- 14726210
TI  - Structure of the D142N mutant of the family 18 chitinase ChiB from Serratia
      marcescens and its complex with allosamidin.
AB  - Catalysis by ChiB, a family 18 chitinase from Serratia marcescens, involves a
      conformational change of Asp142 which is part of a characteristic
      D(140)XD(142)XE(144) sequence motif. In the free enzyme Asp142 points towards
      Asp140, whereas it rotates towards the catalytic acid, Glu144, upon ligand
      binding. Mutation of Asp142 to Asn reduced k(cat) and affinity for allosamidin, a
      competitive inhibitor. The X-ray structure of the D142N mutant showed that Asn142
      points towards Glu144 in the absence of a ligand. The active site also showed
      other structural adjustments (Tyr10, Ser93) that had previously been observed in
      the wild-type enzyme upon substrate binding. The X-ray structure of a complex of
      D142N with allosamidin, a pseudotrisaccharide competitive inhibitor, was
      essentially identical to that of the wild-type enzyme in complex with the same
      compound. Thus, the reduced allosamidin affinity in the mutant is not caused by
      structural changes but solely by the loss of electrostatic interactions with
      Asp142. The importance of electrostatics was further confirmed by the pH
      dependence of catalysis and allosamidin inhibition. The pH-dependent apparent
      affinities for allosamidin were not correlated with k(cat), indicating that it is
      probably better to view the inhibitor as a mimic of the oxazolinium ion reaction
      intermediate than as a transition state analogue.

PMID- 14726211
TI  - Structural features of the initiator of replication protein RepB encoded by the
      promiscuous plasmid pMV158.
AB  - The promiscuous rolling circle (RC)-replicating plasmid pMV158 encodes the 210
      amino-acid initiator of replication protein, RepB. The protein relaxes
      supercoiled cognate DNA in a topoisomeraseI-like manner. A new vector and
      procedure for overproduction, scaling-up, and purification of the protein has
      been developed. RepB purified as a hexamer in solution, as shown by analytical
      ultracentrifugation assays. Circular dichroism (CD) of RepB indicated that the
      protein has an estimated content of around 33% alpha-helices and 20% beta
      strands. Characterisation of temperature-induced transitions of the protein
      showed an irreversible change in the spectra when the temperature was raised
      above 35 degrees C, indicating that the protein undergoes a conformational change
      that could account for the relatively high optimal temperature of the RepB
      mediated cleavage.

PMID- 14726212
TI  - A pattern of protein expression in peripheral blood mononuclear cells
      distinguishes rheumatoid arthritis patients from healthy individuals.
AB  - We compared the expression levels of proteins in peripheral blood mononuclear
      cells (PBMCs) of healthy control individuals to those of patients diagnosed with
      rheumatoid arthritis (RA) using a proteomics approach. Using two-dimensional
      electrophoresis we identified 18 proteins that were 2-fold or more highly
      expressed in patients than in controls, and 11 proteins that were 2-fold or more
      highly expressed in controls than in patients. Some of these differentially
      expressed proteins, identified by MALDI-TOF spectrometry, have previously been
      shown to play a potential role in the pathogenesis of RA. Hierarchical cluster
      analyses of the data segregated the samples into two groups, one which contained
      only controls and the other which contained only patients, and was used to
      compare the expression pattern of these 29 proteins in individual samples with
      the median expression pattern determined in the healthy control and in the RA
      patient groups. This analyses was able to predict whether a sample was derived
      from a rheumatoid arthritis patient or from a healthy individual, suggesting that
      a comparison of such protein expression patterns may be of diagnostic value.

PMID- 14726213
TI  - Distributed subunit interactions in CheA contribute to dimer stability: a
      sedimentation equilibrium study.
AB  - The structural domains of the Escherichia coli CheA protein resemble 'beads on a
      string', since the N-terminal phosphate-accepting (P) domain is joined to the
      CheY/CheB-binding (B) domain through a flexible linker, and the B domain is in
      turn joined to the C-terminal dimerization/catalytic/regulatory domains by a
      second intervening linker. Dimerization occurs primarily via interactions between
      two dimerization domains, which is required for CheA trans-autophosphorylation.
      In this study, sedimentation equilibrium was used to demonstrate significant
      subunit interactions at secondary sites in the two naturally occurring (full
      length and short) forms of CheA (CheA(1-654) or CheA(L), and CheA(98-654) or
      CheA(S)) by contrasting the dimerization of CheA(L) and CheA(S) to CheA(T), an
      engineered form that lacked the P domain entirely. The estimated dimer
      dissociation constant (K(1,2)) for CheA(T) (3.1 microM) was weaker than K(1,2)
      for CheA(L) (0.49 microM), which was attributed to the P domain-catalytic domain
      interactions that were present in CheA(L) but not CheA(T). In contrast, CheA(S)
      dimerization was unexpectedly stronger (K(1,2) approximately 20 nM), which arose
      through interactions between two P domain remnants in the CheA(S) dimer. This
      conclusion was supported by the results of sedimentation equilibrium experiments
      conducted with P domains and P domain remnants expressed in the absence of the
      dimerization/catalytic/regulatory domains. The P domain remnant had a measurable
      tendency to self-associate; the full-length P domain did not. Hydrophobic forces
      probably drive this interaction, since hydrophobic amino acids buried in the
      intact P domain are solvent-exposed in CheA(S). Also, the nascent N-terminus of
      CheA(S) bound to the phosphatase (CheZ) more effectively, a conclusion based on
      the demonstrably greater ability of the P domain remnant to co-sediment CheZ,
      compared to the intact P domain.

PMID- 14726214
TI  - NO-1886 inhibits size of adipocytes, suppresses plasma levels of tumor necrosis
      factor-alpha and free fatty acids, improves glucose metabolism in high-fat/high
      sucrose-fed miniature pigs.
AB  - The synthetic compound NO-1886 is a lipoprotein lipase activator that has been
      proven to be highly effective in lowering plasma triglycerides and elevating high
      density lipoprotein cholesterol. Recently, we found that NO-1886 also had a
      plasma glucose-reducing action in high-fat/high-sucrose diet-induced diabetic
      rabbits. In the current study, we investigated the effects of NO-1886 on the
      morphology of adipocytes, plasma levels of tumor necrosis factor-alpha (TNF
      alpha) and free fatty acids (FFA) in miniature pigs fed a high-fat/high-sucrose
      diet. Our results showed that feeding a high-fat/high-sucrose diet to miniature
      pigs increased the size of adipocytes, and the plasma levels of TNF-alpha, FFA,
      and glucose. This diet also induced insulin resistance and impaired the acute
      insulin response to glucose loading. Supplementing 1% NO-1886 to the high
      fat/high-sucrose diet inhibited adipocyte enlargement, and suppressed plasma
      levels of TNF-alpha, FFA, and glucose. The decrease in plasma TNF-alpha and FFA
      was simultaneous with the decrease in plasma glucose. We also found an increased
      whole body glucose clearance and an increased acute insulin response to
      intravenous glucose loading by NO-1886 supplementation. These data suggest that
      NO-1886 improves the glucose metabolism in high-fat/high-sucrose diet-induced
      diabetic minipigs by decreasing fat deposit, and suppressing plasma TNF-alpha and
      FFA levels. Therefore, NO-1886 is potentially beneficial for the treatment of
      insulin-resistant syndrome.

PMID- 14726215
TI  - Role of potassium channels in the nitric oxide-independent vasodilator response
      to acetylcholine.
AB  - Stimulation of vascular endothelial muscarinic receptors by acetylcholine (ACh)
      leads to the formation of an endothelium-derived relaxing factor (EDRF), which is
      generally accepted to be nitric oxide (NO). Recent evidence, however, suggests
      that NO may be only one of several EDRFs mediating the vasodilator response to
      ACh. Since this NO-independent vasodilator response to ACh has been hypothesized
      to be dependent upon K(+) channel activation, the current study was undertaken to
      investigate the role of K(+) channels in mediating the hindlimb vasodilator
      responses to ACh in vivo. Additionally, since variations in vascular tone can
      complicate the analysis of responses, the level of vascular tone was maintained
      at a similar level throughout the study so that responses could be compared
      directly. The results of the present study demonstrate that the vasodilator
      response to ACh possesses a significant component that is independent of NO
      production. The K(Ca) channel blockers charybdotoxin and apamin, but not K(+)-ATP
      channel blocker U37883A or the COX antagonist meclofenamate, attenuated the NO
      independent component of the vasodilator response to ACh. This suggests that
      K(Ca) channels, but not K(+)-ATP channels or COX products, are involved in
      mediating the L-NAME resistant response to ACh. Further, the inhibition of the
      ACh vasodilator response by the K(+)-ATP opener BRL55834 suggests that the
      response is dependent upon membrane hyperpolarization. These data suggest that
      the mechanism mediating ACh responses in the hindlimb vascular bed of the rat are
      complex and may involve several signaling pathways.

PMID- 14726216
TI  - Nipradilol inhibits atmospheric pressure-induced cell proliferation in human
      aortic smooth muscle cells.
AB  - Hypertension is a major risk factor for atherosclerosis and the genesis of
      cardiovascular and cerebrovascular diseases. Therefore, the protection of
      atherosclerosis progression is one of the purpose of an anti-hypertensive
      treatment in vascular system. Nitric oxide (NO)-releasing drugs have been
      reported to have an inhibitory effect on shear stress-induced extracellular
      signal-regulated kinase (ERK) activation in endothelial cells. For further
      understanding of the effects of these drugs, the present study focused on the
      effects on intracellular signal transduction and cell proliferation in cultured
      human aortic smooth muscle cells (HASMC) under high atmospheric pressure. Three
      hours of 160-mmHg atmospheric pressure resulted in an approximately 380% increase
      in cell proliferation compared to non-pressurized controls. Nipradilol (3,4
      dihydro-8-(2-hydroxy-3-isopropylaminoproxy)-3-nitroxy-2H-1-benzopyran) (10(-6)M)
      demonstrated approximately 40% reduction in cell proliferation compared to that
      shown by pressurized HASMC as a vehicle control. Three hours of 160-mmHg
      atmospheric pressure resulted in a 25% increase in the amount of activated ERKs.
      Nipradilol (10(-6)M) demonstrated approximately a 26% reduction in the amount of
      activated ERKs. NO(x) concentration under the presence of nipradilol (10microM)
      with HASMC resulted in a 7.2microM of NO production and was 2.4-fold more than
      that from no dug control (3.0microM). An administration of L-NAME (10(-4)M)
      supplemented with Nipradilol (10(-6)M) did not show any significant effect on
      cell proliferation. From these observations, we concluded that nipradilol has an
      anti-proliferative effect on HASMC under high atmospheric pressure. Nipradilol
      may act as a nitric oxide inducer from HASMC and suspected to work as a
      supplement to mitigate the impaired endothelial cell function caused by
      hypertension.

PMID- 14726217
TI  - The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric
      oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice
      stimulated by lipopolysaccharide (LPS).
AB  - Morbidity and mortality rates are very high in obstructive jaundice when it is
      associated with sepsis and multiple organ failure. Nitric oxide (NO) formation
      and increased expression of inducible nitric oxide synthase (iNOS) also take
      place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial
      effect by demonstrating anti-inflammatory activity such as inhibits cytokine
      expression/release, inhibiting the adhesion molecule expression and inhibiting
      nuclear factor kappa B (NFkappaB). The aim of this study was to investigate the
      effects of NAC on liver and renal tissue iNOS, and liver tissue lipid
      peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We
      randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group
      C: OJ+NAC; group D: OJ+LPS (Escherichia coli LPS serotype L-2630, 100mg, Sigma)
      group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously
      100mg/kg. LPS was injected intraperitoneally and then at the tenth day we
      sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase
      decreased in groups B-D when compared to group A. After the administration of NAC
      (groups C-E), liver MDA levels decreased, tissue ATPase levels increased as
      compared to other groups. The liver and renal tissue iNOS expression was
      increased in groups B, D, and F. After the administration of NAC (groups C-E) the
      liver and renal tissue iNOS expression were decreased. Our results indicated that
      NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression
      via lipid peroxidation in liver and renal tissue; if it was administrated before
      LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if
      there was established endotoxemia in OJ.

PMID- 14726218
TI  - Antinociceptive and anti-inflammatory properties of the hydroalcoholic extract of
      stems from Equisetum arvense L. in mice.
AB  - In this study, antinociceptive and anti-inflammatory effects of hydroalcoholic
      extract of stem from Equisetum arvense in mice were evaluated. The extract (10,
      25, 50 and 100mgkg(-1), i.p.), reduced the writhing induced by acetic acid in 49,
      57, 93 and 98%, respectively. In the formalin test, 50 and 100mgkg(-1) (i.p.)
      extract, reduced in 80 and 95% the licking activity in the first phase, but in
      the second phase only the latter dose diminished the licking time (35%). In both
      phases, naloxone failed to revert the analgesic effect of the extract. In the hot
      plate test, the extract at 100 and 200mgkg(-1) does not change the latency to
      licking or jumping. In the carrageenan-induced paw oedema, the extract at 50mgkg(
      1), reduced the paw oedema 2h (25%) and 4h (30%) after carrageenan
      administration. The dose of 100mgkg(-1) caused reduction of the paw oedema (29%)
      only 4h after carrageenan administration. These results indicate that this
      extract exhibits an antinociceptive effect in chemical models of nociception
      which is not related to the opioid system, as well as anti-inflammatory
      properties.

PMID- 14726219
TI  - Anti-inflammatory effects of fructose-1,6-bisphosphate on carrageenan-induced
      pleurisy in rat.
AB  - In the present study, we evaluated the effect of fructose-1,6-bisphosphate (FBP),
      a high energy intermediate metabolite of glycolysis, in an acute model of lung
      injury. Injection of carrageenan into the pleural cavity of rats elicited an
      acute inflammation response characterized by a fluid accumulation in the pleural
      cavity which contained a large number of polymorphonuclear neutrophils. FBP
      (500mg/kg) attenuated the inflammation parameters: exudate volume, total
      leukocytes and the number of polymorphonuclear leukocytes, but the protein
      concentration in the exudate was not significantly affected by treatment with
      FBP. The precise site and mechanism of the anti-inflammatory effect was not
      addressed, considering the diverse pharmacological actions of FBP. This drug has
      anti-inflammatory actions suggesting that it may represent a novel strategy for
      the modulation of inflammatory response.

PMID- 14726220
TI  - Effect of vitamins C and E on cognitive function in mouse.
AB  - The aim of this study was to verify the role of Vitamins C and E on the cognitive
      function of young and aged mice. First and second groups of young animals (aged 3
      months) received either Vitamin E (250mg/kg per day) or Vitamin C (300mg/kg per
      day) for 60 days. Third group was treated with the combination of Vitamin E
      (250mg/kg per day) and Vitamin C (300mg/kg per day) for 60 days. The control
      group received only vehicle. The aged animal group (aged 15 months) were treated
      as the young group. Passive avoidance method was used for the assessment of
      cognitive function in both young and aged animals. The results indicated a
      significant improvement in the cognitive function of aged mice while there were
      no significant changes in young animals.

PMID- 14726221
TI  - (-)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine
      induced dopamine release or potassium-induced noradrenaline release, from rat
      brain synaptosomes.
AB  - The effect of (-)-deprenyl (selegiline), a therapeutic agent for Parkinson's
      disease, on the tyramine-induced release of catecholamine from rat brain
      synaptosomes was studied using a superfusion system. Tyramine (10(-7) to 10(-5)M)
      enhanced the release of [3H]noradrenaline (NA) and [3H]dopamine (DA) from
      forebrain and striatal synaptosomes in a dose-dependent manner. (-)-Deprenyl
      (5x10(-5)M) had no effect on spontaneous catecholamine release, suggesting that
      it has no tyramine-like catecholamine releasing effect. Pretreatment with (-)- or
      (+)-deprenyl (5x10(-5)M) significantly prevented the tyramine (10(-6)M)-induced
      NA release, but not DA release. The inhibitory action of (-)-deprenyl was not
      observed on potassium (15mM)-induced NA release. (-)-Desmethyldeprenyl (5x10(
      5)M), a metabolite of (-)-deprenyl, and a monoamine oxidase-A (MAO-A) inhibitor,
      clorgyline (5x10(-5)M), failed to block the tyramine-induced NA and DA release.
      Although (+)-deprenyl, a potent DA uptake inhibitor, did not inhibit tyramine
      induced DA release, a catecholamine uptake inhibitor nomifensine (5x10(-5)M) did.
      In summary, (-)-deprenyl at a dose inhibiting tyramine-induced NA release did not
      have any effect on tyramine-induced DA release or potassium-induced NA release.

PMID- 14726222
TI  - Retrospective analysis of adverse drug reactions induced by gemcitabine treatment
      in patients with non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the
      world. Traditional chemotherapy for advanced NSCLC is often considered
      excessively toxic. Recent clinical trials documented that gemcitabine may
      represent a good therapeutical option in patients with NSCLC. Aim of our research
      was to retrospectively evaluate the adverse effects induced by gemcitabine in
      patients with NSCLC from 1 January 1997 to 31 December 2002, in clinical records
      of Oncology Divisions of "S. Giovanni di Dio" Hospital of Crotone, "Ospedali
      Riuniti" Hospital of Reggio Calabria, Hospital of Paola, and in Pneumological
      Oncology Division of "Mariano Santo" Hospital of Cosenza, Italy. Clinical records
      of patients treated with gemcitabine (1000mgm(-2) on days 1 and 8) were reviewed
      and following data were obtained: sex and age of the patients, histologic
      diagnosis and disease stage, World Health Organisation (WHO) performance status
      and toxic effects induced by gemcitabine. We reported that 71.6% of NSCLC
      patients (age range 48-77 years; 135 males, 27 females; performance status 0=53,
      1=109) were eligible for our study. Side effect of gemcitabine involved
      gastrointestinal system (nausea, vomiting and diarrhoea) and only in the last
      cycles (VIII-XI) emopoiethic system (leukopenia, neutropenia, thrombocytopenia
      and anemia). Grade IV vomiting occurred in three patients, thrombocytopenia in
      two. Grade III leukopenia was observed in three patients. Other toxicities were
      mild. None of the patients died during chemotherapy. In conclusion, these data
      showed that gemcitabine present a very good tolerability in patients with NSCLC.
      Therefore, it could be considered as a new therapeutic agents to use as first
      line therapy for this disease.

PMID- 14726223
TI  - Inhibitory effect of polypeptide from Chlamys farreri on ultraviolet A-induced
      oxidative damage on human skin fibroblasts in vitro.
AB  - We have previously reported that polypeptide from Chlamys farreri (PCF) inhibits
      the oxidative damage of ultraviolet A (UVA) on HeLa cells in vitro [Acta Pharm.
      Sin. 23 (2002) 961]. To further elucidate a possible role for PCF on UVA-damaged
      normal human cells, we established the oxidative damage models of normal human
      dermal fibroblasts (NHDF) exposed to UVA to study the protective effect of PCF on
      human dermal fibroblasts in vitro. In this study, 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cell
      viability. The intracellular superoxide dismutase (SOD), glutathione peroxidase
      (GSH-px), catalase (CAT), xanthine oxidase (XOD), malondialdehyde (MDA), reactive
      oxygen species (ROS), total antioxidative capacity (T-AOC), and anti-superoxide
      anion capacity (A-ASC) were measured. The effect of PCF on UVA-induced apoptosis
      were investigated by Annexin V-FITC assay. Intracellular calcium was determined
      with the calcium-sensitive fluorochrome Fluo-3, and mitochondrial transmembrane
      potential with rhodamine 123. Comet assay was employed to detect the UVA-induced
      DNA damage. The ultrastructure of cell was observed under transmission electron
      microscope. The results indicated that PCF could greatly enhance the viability of
      NHDF and markedly promote SOD, GSH-px, T-AOC, and A-ASC, while the amounts of MDA
      and ROS, the activity of XOD were decreased. PCF could inhibit UVA-induced
      apoptosis and DNA damage in NHDF. The concentration of cellular free calcium was
      decreased and the mitochondrial transmembrane potential was increased by PCF. In
      ultrastructure of NHDF, PCF could greatly decrease UVA-induced damage, especially
      membrane. Our results suggest that the supplementation of PCF appears to reduce
      the UVA-induced normal human dermal fibroblasts damage efficiently. It may be
      involved in the PCF's abilities of scavenging oxygen free radical, inhibiting
      lipid peroxidation, increasing antioxidative enzymes, decreasing intracellular
      calcium and protection of membrane structure in NHDF irradiated by UVA.

PMID- 14726224
TI  - Pharmacokinetics and a simulation model of colforsin daropate, new forskolin
      derivative inotropic vasodilator, in patients undergoing coronary artery bypass
      grafting.
AB  - Colforsin daropate, a water-soluble forskolin derivative, is an adenyl cyclase
      activator with positive inotropic and vasodilatory effects that are useful in the
      treatment of ventricular dysfunction. We investigated the pharmacokinetics of
      colforsin daropate in cardiac surgery patients and performed simulations to
      determine the dosage necessary to maintain an effective plasma concentration
      following cardiopulmonary bypass. In six patients undergoing coronary artery
      bypass graft, colforsin daropate (0.01mgkg(-1)) was administered immediately
      after separation from cardiopulmonary bypass. Arterial blood was sampled over the
      next 16h and plasma concentrations of colforsin daropate and its initial active
      metabolite were determined by gas-chromatography. Extended nonlinear least
      squares regression was used to fit a three-compartment model to each patient's
      data. Distribution half-life (t(1/2alpha)) was 3.9+/-1.1min, metabolic half-life
      (t(1/2beta)) was 1.9+/-0.7h, and elimination half-life (t(1/2gamma)) was 95.3+/
      15.2h. Central-compartment volume was 591.0+/-42.8mlkg(-1), volume distribution
      was 2689.2+/-450.6mlkg(-1), and elimination clearance was 27.7+/-14.7mlkg(-1)min(
      1). In the pharmacokinetic simulation model, 0.5, 0.75, and 1.0microgkg(-1)min(
      1) continuous infusion of colforsin daropate produce effective concentration (5
      10ngml(-1)) within 30, 20, and 10min, respectively following administration. An
      initial active metabolite of decreased rapidly to less than 1.0ngml(-1) within
      the first 10min.A colforsin daropate infusion of 0.7-1.0microgkg(-1)min(-1) for
      10-20min followed by 0.5microgkg(-1)min(-1) continuous infusion is recommended to
      produce an effective concentration (5-10ngml(-1)) within 10-20min and to maintain
      a therapeutic concentration throughout the administration period after
      cardiopulmonary bypass.

PMID- 14726225
TI  - The degree of predictivity in pilot studies on six subjects in bioequivalence
      trials.
AB  - This study, based on computer simulations, analysed the degree of predictivity of
      pilot trials on six subjects, with the idea of a further pivotal trial on 18 or
      more volunteers aimed at assessing bioequivalence. Volunteers enrolled in 10
      pivotal bioequivalence trials were considered. For every trial, a thousand
      bootstrap samples were generated to simulate trials with six subjects, while
      keeping a balanced design for sequence, period and formulation. Then a standard
      ANOVA for crossover trials, with 90% confidence intervals for the ratios, was
      done on C(max) and AUC for each simulated trial. The number of subjects needed to
      achieve bioequivalence was based on the residual error of the ANOVA. When this
      number was smaller or equal in the case of bioequivalence, or larger in the case
      of insufficient evidence to conclude on bioequivalence, to the number of the
      subjects enrolled in the original trial, the subgroup was considered predictive.
      Otherwise it was considered non-predictive.The average predictivity index,
      calculated by dividing the number of predictive findings by the total number of
      subgroups, in our case 1000, and multiplying the result by 100, was 71.1% for
      C(max) and 82.9% for AUC. Results of the simulations suggest that pilot trials on
      six volunteers can be useful for predicting the pool size of volunteers in
      bioequivalence trials, and for in vivo-in vitro correlation studies in
      pharmaceutical development strategy.

PMID- 14726226
TI  - Effect of water extract of Turkish propolis on tuberculosis infection in guinea
      pigs.
AB  - Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to
      investigate the effect of water extract of propolis (WEP). After subcutaneous
      inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid
      (n=5) or saline (n=6) as placebo and were sacrificed 30 days later. Formation of
      necrosis was less prominent in the group treated with WEP, but was not
      statistically significant (P>0.05). The granuloma formation in the same group was
      more prominent than the placebo and isoniazid groups; however, this finding
      failed to reach statistical significance by the Kruskal-Wallis test (P>0.05).
      These findings suggest that Turkish WEP may have a limited effect on the
      development of tuberculosis infection in this guinea-pig model.

PMID- 14726227
TI  - Urinary transforming growth factor-beta 1 in various types of nephropathy.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent multifunctional
      polypeptide that is involved in normal renal function and in the development of
      glomerular sclerosis. It is also an important mediator of the immune and anti
      inflammatory responses. The purpose of this study was to examine whether the
      measurement of urinary TGF-beta1 excretion in patients with different types of
      renal diseases and in newly diagnosed type 1 diabetes mellitus represents a non
      invasive tool to evaluate disease activity and to monitor response to therapy. We
      studied the urinary excretion of TGF-beta1 in 57 nephropathic patients divided in
      different groups according to the underlying disease: 15 had mesangial
      glomerulonephritis (IgAGN), 9 membranous glomerulonephritis (MGN), 7 rapidly
      progressive glomerulonephritis (RPGN), 8 systemic lupus erythematosus (SLE), 9
      interstitial nephritis (IN), 9 chronic renal failure (CRF). TGF-beta1 was also
      measured in 38 patients with type 1 (insulin-dependent) diabetes mellitus (12
      with newly diagnosed diabetes, 26 long-standing diabetes) and 31 healthy
      controls. Total urinary TGF-beta1 concentration was assayed by enzyme-linked
      immunoassay (ELISA), and expressed as a ratio to urinary creatinine
      concentration. The urinary TGF-beta1 levels were compared with the findings of
      biopsy and clinical parameters. Urinary TGF-beta1 excretion was significantly
      increased in all groups except MGN, IN and CRF. In non-diabetic patients, urinary
      TGF-beta1 levels correlated with crescent formation, floccular adhesion and
      mesangial proliferation, but not with the degree of tubulo-interstitial fibrosis.
      Urinary TGF-beta1 levels did not correlate with indices of renal function (serum
      creatinine, glomerular filtration rate (GFR), albumin excretion rate [AER]).
      Among diabetic patients, HbA(1C) significantly correlated with TGF-beta1 urinary
      excretion. Urinary TGF-beta1 levels may represent a valid indicator of acute
      glomerular flogosis associated with mesangial proliferation in
      glomerulonephrities. In newly diagnosed diabetic patients, hyperglycaemia seems
      to represent the principal factor leading to TGF-beta1 overproduction. Follow-up
      studies of urinary TGF-beta1 levels measured during optimal glycaemic control are
      necessary to clarify the relationship between hyperglycaemia and TGF-beta1
      excretion.

PMID- 14726228
TI  - High growing ability of Vibrio vulnificus biotype 1 is essential for production
      of a toxic metalloprotease causing systemic diseases in humans.
AB  - Vibrio vulnificus biotype 1, a causative agent of fatal septicemia or wound
      infection in humans, is known to produce a toxic metalloprotease as an important
      virulence determinant. V. vulnificus biotype 2 (serovar E), a primary eel
      pathogen, was found to elaborate an extracellular metalloprotease that was
      indistinguishable from that of biotype 1. The potential of V. vulnificus biotype
      1 for production of the metalloprotease was compared with biotype 2 and other
      human non-pathogenic Vibrio species (Vibrio anguillarum and Vibrio
      proteolyticus). When cultivated at 25 degrees C in tryptone-yeast extract broth
      supplemented with 0.9% NaCl, all bacteria multiplied sufficiently and secreted
      significant amounts of the metalloprotease. However, at 37 degrees C with 0.9%
      NaCl, V. anguillarum neither grew nor produced the metalloprotease. In human
      serum, only V. vulnificus biotype 1 revealed a steady multiplication accompanied
      with production of the extracellular metalloprotease. This prominent ability of
      biotype 1 in growth and protease production may contribute to cause serious
      systemic diseases in humans.

PMID- 14726229
TI  - Patterns of adherence to HEp-2 cells and actin polymerisation by toxigenic
      Corynebacterium diphtheriae strains.
AB  - Corynebacterium diphtheriae strains displayed different degrees of attachment to
      HEp-2 cell monolayers with two distinct adherence patterns, termed localised (LA)
      and diffuse (DA). The LA phenotype predominated over the DA phenotype. The non
      sucrose fermenting strains expressing DA pattern adhered mostly with high index
      values (> or =10bact/cell). Low adhesion index (<10bact/cell) was mainly observed
      among sucrose fermenting strains. The fluorescein isothiocyanate (FITC)-labelled
      phalloidin assay (fluorescent-actin staining test) showed positive results for
      microorganisms of both LA and DA phenotypes. The FITC-labelled C. diphtheriae non
      fimbrial surface proteins 67-72p interacted directly with HEp-2 cell membranes.
      Therefore, toxigenic C. diphtheriae exhibited LA and DA adherence patterns and
      ability to induce actin polymerisation. The experimental evidences also pointed
      to 67-72p as putative adhesins of C. diphtheriae to HEp-2 cells.

PMID- 14726230
TI  - Molecular-genetic peculiarities of classical biotype Vibrio cholerae, the
      etiological agent of the last outbreak Asiatic cholera in Russia.
AB  - Molecular-genetic properties of classical biotype Vibrio cholerae strains that
      caused the Asiatic cholera outbreak in 1942 in Russia have been investigated for
      the first time. Being characterized by high-level production of cholera toxin and
      toxin-coregulated adhesion pili both of which are the major virulence factors,
      all the strains studied, in contrast to the typical cholera pathogens, were
      autographic requiring purine and/or amino acids added to the minimal medium for
      their growth. Moreover, these strains containing the structural gene hapA, as
      shown by the polymerase chain reaction, produced no soluble
      hemagglutinin/protease, which enables the vibrios to get disseminated in the
      environment. The peculiarities of the natural V. cholerae strains elucidated in
      the work are likely to be responsible for the unusual infectious and epidemic
      processes observed during that cholera outbreak.

PMID- 14726231
TI  - Regional differences in the early mucosal immune response induced by primary
      inoculation of mice with respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the most important cause of respiratory
      tract infection in infants. Little is known about the characteristics of critical
      immunologic inductive sites within respiratory-associated lymphoid tissues (RALT)
      upon RSV infection. We examined the kinetics and characteristics of early mucosal
      RSV-specific immune responses after primary inoculation of mice. We found that
      the initial production of virus-specific antibodies was restricted to the
      organized lymphoid tissues of RALT, such as nasal-associated lymphoid tissue
      (NALT), cervical and bronchial lymph nodes (CLN and BLN). In addition, virus
      specific IgM was produced by B cells resident in CLN and BLN, but not NALT, of
      mice. Finally, we observed regional differences in the pattern of RSV-specific
      antibodies produced by RALT; B cells within NALT and CLN produced equivalent
      quantities of virus-specific IgG2a and IgG2b. However, an IgG2a response
      predominated in BLN. Together these data demonstrate regional differences in the
      early mucosal immune response to RSV. Further understanding of these differences
      may assist the development of RSV vaccines.

PMID- 14726232
TI  - Changes in Salmonella enterica serovar Oranienburg viability caused by NaCl
      induced osmotic stress is related to DNA relaxation by the H-NS protein during
      host infection.
AB  - The NaCl sensitivity of Salmonella enterica serovar Oranienburg strains depends
      on their origin. We found previously that food- and patient-origin isolates in an
      outbreak were, respectively, NaCl-resistant and NaCl-sensitive, and the NaCl
      resistant strain of food-origin isolates became NaCl-sensitive after passage of
      the strain through mice [FEMS Microbiol. Lett. 212 (2002) 87]. Here, we report
      that this phenotypic difference is mainly dependent on topological changes
      regulated by H-NS, a bacterial histone-like nucleoid protein that binds non
      specifically to DNA. That is, this phenotypic difference was caused by changes in
      DNA topology during infection of the host. Based on these findings, we propose
      this mechanism has a key role in promoting the survival of Salmonella under
      osmotic stress.

PMID- 14726233
TI  - Requirement of hydD, hydE, hypC and hypE genes for hydrogenase activity in
      Helicobacter pylori.
AB  - Helicobacter pylori possesses a membrane-bound, nickel containing, hydrogen
      uptake hydrogenase enzyme; its synthesis requires structural as well as accessory
      proteins, the latter needed for the complete maturation of the enzyme. Our lab
      previously characterized mutants in the accessory hyp genes, hypA, hypB, hypD and
      hypF that were all severely affected for hydrogenase activity, and in some cases
      (hypA and hypB mutants) also affected for urease activity. This finding prompted
      us to disrupt the two remaining unstudied hyp genes of H. pylori, hypC and hypE,
      in order to see if the same pleiotropic effect would be observed. In both mutants
      hydrogenase activity was abolished but urease activity remained unaffected.
      Addition of 5 microM nickel into the growth medium partially restored the
      hydrogenase activity in the hypE mutant and to a lesser extent in the hypC
      mutant. In addition, we also disrupted the genes HP0634 (referred as hydD in the
      H. pylori 26695 genome database) and HP0635 (whose function was unknown, referred
      to here as hydE) to address their possible roles in the hydrogenase
      synthesis/maturation process. In both cases, hydrogenase activities were
      abolished and addition of nickel could not restore the activity, suggesting that
      these proteins are involved in the hydrogenase synthesis process rather than in
      nickel mobilization/insertion steps.

PMID- 14726234
TI  - Pharmacological inhibition of Mannheimia haemolytica lipopolysaccharide and
      leukotoxin-induced cytokine expression in bovine alveolar macrophages.
AB  - The inflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1
      beta (IL-1beta), and interleukin-8 (IL-8) are believed to contribute to the
      pathogenesis of lung injury in bovine pneumonic mannheimiosis (BPM) caused by
      Mannheimia (Pasteurella) haemolytica. Inflammatory cytokines may, therefore,
      represent therapeutic targets to be modulated for the purpose of treating or
      preventing this important disease of cattle. The purpose of this study was to
      evaluate the ability of six pharmacological agents to suppress the expression of
      TNFalpha, IL-1beta, and IL-8 genes and proteins in bovine alveolar macrophages
      (AM) exposed to M. haemolytica lipopolysaccharide (LPS) and leukotoxin (LktA) in
      vitro. The compounds tested included dexamethasone (DEX), tetrahydropapaveroline
      (THP), pentoxifylline (PTX), rolipram (ROL), SB203580 (SB), and thalidomide
      (THL). Cytokine expression was induced by the addition of purified M. haemolytica
      LPS and LktA to AM cell cultures following pretreatment with inhibitor compounds.
      Secretion of TNFalpha, IL-1beta, and IL-8 proteins into the cell culture
      supernatant was measured using enzyme-linked immunosorbent assays, and steady
      state accumulation of cytokine-specific mRNA was measured by northern blot
      analysis. Dose-dependent inhibition of cytokine secretion occurred in response to
      pretreatment of AM with DEX (TNFalpha, IL-1beta, IL-8), THP (TNFalpha, IL-1beta,
      IL-8), PTX (TNFalpha, IL-1beta, IL-8), ROL (TNFalpha, IL-1beta), and SB
      (TNFalpha, IL-8). Significant dose-dependent inhibition of cytokine mRNA
      expression occurred in response to pretreatment with DEX (TNFalpha, IL-1beta, IL
      8), THP (TNFalpha, IL-1beta, IL-8), and PTX (TNFalpha). DEX was the most
      effective inhibitor by far; pretreatment with this compound yielded greater than
      95% inhibition of cytokine gene and protein expression over a broad range of
      concentrations. These findings demonstrate that DEX, THP, PTX, ROL, and SB are
      capable of suppressing inflammatory cytokine secretion by bovine AM in vitro. If
      pulmonary cytokine secretion may be similarly inhibited in vivo, anti-cytokine
      therapy may represent a novel strategy for the management of BPM.

PMID- 14726235
TI  - Studies on the cytotoxic effects of Propionibacterium acnes strains isolated from
      cornea.
AB  - Eukaryotic tissue culture appears to be a suitable model for measuring the
      bacterial cytotoxic effect. Propionibacterium acnes strains were isolated from
      corneal tissue removed by keratoplastic surgery from patients with corneal
      dystrophy or bullous keratopathy. The cytotoxic effect of the filtrates of 10 P.
      acnes strains were studied by means of measuring the decrease of the
      mitochondrial dehydrogenase activities of viable epithelial (HeLa) and
      fibroblastic (BHK-21) cell cultures. A time and concentration dependent,
      reversible cytotoxic effect was detected in both tissue types. The results also
      showed that strains of P. acnes are capable of surviving anaerobic conditions for
      as long as 8 months and suggest that production cytotoxic effects during the long
      persistence it may harm human tissue.

PMID- 14726238
TI  - Plant waxy bloom on peas affects infection of pea aphids by Pandora neoaphidis.
AB  - This study examined the effects of the surface wax bloom of pea plants, Pisum
      sativum, on infection of pea aphids, Acyrthosiphon pisum, by the fungal pathogen
      Pandora neoaphidis. In prior field surveys, a higher proportion of P. neoaphidis
      killed pea aphids (cadavers) had been observed on a pea line with reduced wax
      bloom, as compared with a sister line with normal surface wax bloom. Laboratory
      bioassays were conducted in order to examine the mechanisms. After plants of each
      line infested with aphids were exposed to similar densities of conidia, the rate
      of accumulation of cadavers on the reduced wax line was significantly greater
      than on the normal wax bloom line; at the end of the experiment (13d), the
      proportion of aphid cadavers on the reduced wax line was approximately four times
      that on the normal wax bloom line. When plants were exposed to conidia first and
      then infested with aphids, the rate of accumulation of cadavers was slightly but
      significantly greater on the reduced wax line, and infection at the end of the
      experiment (16d) did not differ between the lines. When aphids were exposed first
      and then released onto the plants, no differences in the proportion of aphid
      cadavers were observed between the pea lines. Greater infection of pea aphid on
      reduced wax peas appears to depend upon plants being exposed to inoculum while
      aphids are settled in typical feeding positions on the plant. Additional
      experiments demonstrated increased adhesion and germination by P. neoaphidis
      conidia to leaf surfaces of the reduced wax line as compared with normal wax
      line, and this could help explain the higher infection rate by P. neoaphidis on
      the reduced wax line. In bioassays using surface waxes extracted from the two
      lines, there was no effect of wax source on germination of P. neoaphidis conidia.

PMID- 14726239
TI  - Establishment of the new genus Paranosema based on the ultrastructure and
      molecular phylogeny of the type species Paranosema grylli Gen. Nov., Comb. Nov.
      (Sokolova, Selezniov, Dolgikh, Issi 1994), from the cricket Gryllus bimaculatus
      Deg.
AB  - The ultrastructure of the microsporidian parasite Nosema grylli, which
      parasitizes primarily fat body cells and haemocytes of the cricket Gryllus
      bimaculatus (Orthoptera, Gryllidae) is described. All observed stages (meront,
      meront/sporont transitional stage ("second meront"), sporont, sporoblast, and
      spore) are found in direct contact with the host cell cytoplasm. Nuclei are
      diplokaryotic during almost all stages of the life cycle, but a brief stage with
      one nucleus containing an abundance of electron-dense material is observed during
      a "second merogony." Sporogony is disporous. Mature spores are ovocylindrical in
      shape and measure 4.5+/-0.16micromx2.2+/-0.07 microm (n=10) on fresh smears and
      3.3+/-0.06 micromx1.4+/-0.07 microm (n=10) on ultrathin sections. Spores contain
      15-18 coils of an isofilar polar filament arranged in one or two layers.
      Comparative phylogenetic analysis using rDNA shows N. grylli to be closely
      related to another orthopteran microsporidian, Nosema locustae, and to Nosema
      whitei from the confused flour beetle, Tribolium confusum. Antonospora scoticae,
      a parasite of the communal bee Andrena scotica, is a sister taxon to these three
      Nosema species. The sequence divergence and morphological traits clearly separate
      this group of "Nosema" parasites from the "true" Nosema clade containing Nosema
      bombycis. We therefore propose to change the generic name of N. grylli and its
      close relative N. locustae to Paranosema n. comb. We leave N. whitei in former
      status until more data on fine morphology of the species are obtained.

PMID- 14726240
TI  - A comparative study of white spot syndrome virus infection in shrimp from India
      and Korea.

PMID- 14726241
TI  - Classification of Homarus americanus hemocytes and the use of differential
      hemocyte counts in lobsters infected with Aerococcus viridans var. homari
      (Gaffkemia).
AB  - Hemocytes of the American lobster (Homarus americanus H. Milne Edwards) were
      classified after examination of Wright-Giemsa stained cytocentrifuge preparations
      by brightfield light microscopy. Eleven hemocyte types were identified using
      morphologic criteria. The classification system was then used to monitor changes
      in the differential hemocyte count (DHC) of lobsters infected with the Gram
      positive coccus Aerococcus viridans var. homari, etiologic agent of gaffkemia.
      The appearance of less mature hemocytes in the DHCs of lobsters in the late
      stages of infection was similar to the 'left shift' of vertebrate inflammation.
      Results from this study suggest that DHCs can be used to assess and characterize
      inflammation in H. americanus and possibly other crustaceans.

PMID- 14726242
TI  - Ultrastructural characteristics and small subunit ribosomal DNA sequence of
      Vairimorpha cheracis sp. nov., (Microspora: Burenellidae), a parasite of the
      Australian yabby, Cherax destructor (Decapoda: Parastacidae).
AB  - This is the first record of a species of Vairimorpha infecting a crustacean host.
      Vairimorpha cheracis sp. nov. was found in a highland population of the
      Australian freshwater crayfish, Cherax destructor. The majority of spores and
      earlier developmental stages of V. cheracis sp. nov. were found within striated
      muscle cells of the thorax, abdomen, and appendages of the crayfish. Only
      octosporoblastic sporogony within sporophorous vesicles (SPVs) was observed.
      Diplokaryotic sporonts separated into two uninucleate daughter cells, each of
      which gave rise to four sporoblasts in a rosette-shaped plasmodium, so that eight
      uninucleate spores were produced within the persistent ovoid SPV. Ultrastructural
      features of stages in the octosporoblastic sequence were similar to those
      described for Vairimorpha necatrix, the type species. Mature spores were pyriform
      in shape and averaged 3.4x1.9 microm in dimensions. The anterior polaroplast was
      lamellar in structure, and the posterior polaroplast vesicular. The polar
      filament was coiled 10-12 times, lateral to the posterior vacuole. The small
      subunit ribosomal DNA (SSU rDNA) of V. cheracis sp. nov. was sequenced and
      compared with other microsporidia. V. cheracis sp. nov. showed over 97% sequence
      identity with Vairimorpha imperfecta and five species of Nosema, and only 86%
      sequence identity with V. necatrix. The need for a taxonomic revision of the
      Nosema/Vairimorpha group of species is discussed.

PMID- 14726243
TI  - Cell line-specific accumulation of the baculovirus non-hr origin of DNA
      replication in infected insect cells.
AB  - Successive viral passage of Spodoptera exigua multicapsid nucleopolyhedrovirus
      (SeMNPV) in the S. exigua cell line Se301 leads to the rapid accumulation of the
      non-hr origin of DNA replication (ori) as large concatemers. Passage of SeMNPV in
      two other S. exigua cell lines, SeUCR1 and SeIZD2109, did not show the
      accumulation of such concatemers. When introduced into SeUCR1 and SeIZD2109
      cells, the non-hr ori concatemers generated in Se301 cells were maintained but
      did not increase. This suggests that the non-hr ori confers a strong selective
      advantage in Se301 cells, but not or to a lesser extent in the other cell lines.
      The cell line-specific accumulation of non-hr ori concatemers might be due to a
      higher intrinsic recombination frequency in Se301 cells and may reflect tissue
      related differences involving some host cell factor(s). Since non-hr ori
      concatemers in Se301 cells were more abundant in intracellular than in
      extracellular viral DNA preparations, episomal replication and the requirement of
      a minimal DNA size for packaging into nucleocapsids is hypothesized.

PMID- 14726244
TI  - Food consumption by Chilo partellus (Lepidoptera: Pyralidae) larvae infected with
      Beauveria bassiana and Metarhizium anisopliae and effects of feeding natural
      versus artificial diets on mortality and mycosis.
AB  - Second and third instar Chilo partellus larvae were infected with Beauveria
      bassiana and Metarhizium anisopliae (both at 1x10(8)conidia/ml) and daily
      consumption of maize leaves was measured. Infection by the fungi was associated
      with reduced mean daily food consumption. Reduction in food consumption became
      evident 3-4 days after treatment with the fungi for second instar larvae and 4-5
      days for third instar larvae. Four conidial concentrations, 1x10(5), 1x10(6),
      1x10(7), and 1x10(8)conidia/ml, were tested against second instar larvae. Food
      consumption dropped by 70-85% when the second instar larvae were treated with the
      fungi at 1x10(8)conidia/ml. Reduction in food consumption by C. partellus larvae
      infected with B. bassiana and M. anisopliae may offset the slow speed of kill of
      the fungi. The effect of artificial versus natural diets on mortality and mycoses
      of second instar larvae treated with the fungi at 1x10(8)conidia/ml was
      determined. Larvae provided with artificial diet suffered little mortality and
      mycoses than larvae provided with maize leaves. The LT(50) was longer for larvae
      provided with artificial diet.

PMID- 14726245
TI  - Microorganisms in the gut of beetles: evidence from molecular cloning.
AB  - We have regularly cultured yeasts from the gut of certain beetles in our ongoing
      research. In this study cloned PCR products amplified from the gut contents of
      certain mushroom-feeding and wood-ingesting beetles in four families (Erotylidae,
      Tenebrionidae, Ciidae, and Passalidae) were sequenced and compared with culture
      results. Cultural techniques detected some yeasts present in the gut of the
      beetles, including a Pichia stipitis-like yeast associated with wood-ingesting
      passalid beetles. Clone sequences similar to several ascomycete yeasts and
      Malassezia restricta, a fastidious basidiomycetous yeast requiring special growth
      media, however, were not detected by culturing. Unexpectedly, phylogenetic
      analysis of additional clone sequences discovered from passalid beetles showed
      similarity to members of the Parabasalia, protists known from other wood
      ingesting insects, termites, and wood roaches. Examination of all gut regions of
      living passalids, however, failed to reveal parabasalids, and it is possible that
      they were parasites in the gut tissue present in low numbers.

PMID- 14726246
TI  - Virus-like particles associated with large foci of heavy hemocytic infiltration
      in cockles Cerastoderma edule from Galicia (NW Spain).

PMID- 14726247
TI  - A simple and rapid procedure to obtain aseptic larvae of the Colorado potato
      beetle, Leptinotarsa decemlineata, for molecular investigations.

PMID- 14726248
TI  - Critical care outreach--the story so far.

PMID- 14726249
TI  - A double concern: Danish grandfathers' experiences when a small grandchild is
      critically ill.
AB  - This paper addresses grandfathers' lived experiences when a new-born or small
      grandchild is critically ill. Grandfathers are marginal in nursing research in
      spite of the fact that intensive care nursing has broadened its perspective from
      being patient-centred to include family-oriented care. A convenience sample of
      seven grandfathers was interviewed once. Using Van Manen's phenomenological
      methodology, the essence of the phenomenon was found to be "a double concern".
      Main themes in this essential theme were: "Being a father and a grandfather" and
      "being in the midst of life and death". Six sub-themes expanded and clarified the
      meaning of these themes. Overall the grandfathers experienced worry and loving
      concern for parents and grandchildren. In life-threatening situations
      grandfathers were scared and felt helpless; they were prepared to console and
      comfort; they always hoped for the best; and they felt like being in the inner
      circle if the health personnel included them when informing about the infant.
      Information and presence generally were of importance for the wellbeing of
      grandfathers. The findings constitute a systematic and thematic description of
      Danish grandfathers' experiences and therefore add to a family-oriented body of
      knowledge for intensive care nursing.

PMID- 14726250
TI  - The needs of significant others within intensive care--the perspectives of
      Swedish nurses and physicians.
AB  - The aim of this study was to describe and compare the views of registered nurses
      (RNs, n=292), enrolled nurses (ENs, n=232) and physicians (PHs, n=79) working in
      intensive care units (ICUs) on the needs of the patients' significant others. The
      questionnaire used was the Critical Care Family Needs Inventory (CCFNI). Data
      were analysed using descriptive and inferential statistics. Four factors were
      revealed: (I) the need to meet professionals who are sensitive when informing and
      listening to significant others, (II) the need to take care of themselves, (III)
      the need to know what is going on, and (IV) the need for continuity as well as
      information about the hospital staffing structure. RNs and ENs scored higher than
      the PHs on factors I-III. On the fourth factor, ENs and PHs scored higher than
      the RNs. The professionals from surgical ICUs scored higher on the third factor
      than the professionals from medical ICUs. In conclusion, to increase the
      understanding of the complexity of the intensive care milieu there is a need for
      further research to illuminate the view of both the healthcare professionals' and
      the critically ill patients' significant others on their interactions with one
      another, for the purpose of increasing collaboration.

PMID- 14726251
TI  - The presence of family during brain stem death testing.
AB  - Prior to 1959, cardiac and respiratory cessation was universally and
      unambiguously accepted as confirming the death of a person [M. Morioka, J. Clin.
      Nurs. 10 (2001) 132; Reconsidering brain death: a lesson from Japan's fifteen
      years of experience, 2001, http://proquest.umi.com/pqdweb]. However, with the
      rapid pace of modern technology and resuscitation techniques, the boundaries
      between life and death have become blurred [J. Bothamley, Organ donation: brain
      stem death, 2000, http://proquest.umi.com/pqdweb; Re-examining death: against a
      higher brain criterion, 1999, http://proquest.umi.com/pqdweb]. As a result, a
      redefinition of death, "brain death" has emerged [M. Brazier, Medicine, Patients
      and the Law, New ed., Penquin Books, London, 1992]. Most families faced with the
      brain stem death of a relative find the concept difficult to understand and have
      trouble in accepting that their relative is actually dead. In Part One of this
      two part series, the needs of families who are facing the brain stem death of a
      family member will be examined and explanations offered as to why families find
      the concept difficult to grasp. In addition, it will also advocate that family
      members are given the choice to be or not to be present during brain stem death
      testing. It is suggested that the presence of family members during brain stem
      death testing not only helps families to accept this concept of death but also
      promotes the grieving process. In Part Two, the barriers that inhibit family
      involvement and presence will be explored and methods for involving family
      proposed.

PMID- 14726252
TI  - Lifelong learning--the key to competence in the intensive care unit?
AB  - With continual advances in technology and changes in medical and nursing practice
      there is a need to continue professional development whilst working within the
      Intensive Care environment. This paper aims to consider why and how nurses
      working within the Intensive Care environment learn knowledge and skills. To
      explore nurses' experiences, a qualitative approach using a semi-structured
      questionnaire comprising open questions was used. The questionnaires were then
      analysed using line by line coding. The findings revealed that intensive care
      nurses learn knowledge and skills continually through a lifelong learning process
      in order to become a competent practitioner. Three themes were identified within
      this process: learning, opportunity, and outcome, all being affected by three
      factors: internal, external and patient-related. It is suggested that in order to
      organise and support effective learning, there needs to be an awareness of all of
      these factors and to be able to overcome the negative aspects to enhance the
      learning experience for all. The ultimate outcome of learning for the intensive
      care nurses was to practice competently in order to deliver high quality patient
      care.

PMID- 14726253
TI  - Clinical guidelines and care protocols.
AB  - Clinical guidelines and care protocols are intended to provide information, based
      on an appraisal of the current best evidence of clinical and cost-effectiveness,
      regarding therapeutic interventions for given conditions. With the establishment
      of the National Collaborating Centre for Nursing as a part of National Institute
      for Clinical Excellence (NICE), it is anticipated that an increasing number of
      clinical guidelines that focus on aspects of nursing care will be developed at a
      national level. The Department of Health also aims to introduce nationally agreed
      multidisciplinary care protocols which will dictate how certain conditions are to
      be managed. These developments have the potential to enhance healthcare provision
      and nursing practice. However, they also introduce potential dilemmas for nurses.
      This paper discusses some of the issues involved in the development and
      implementation of clinical guidelines and care protocols in intensive care
      nursing.

PMID- 14726254
TI  - Update on statins.

PMID- 14726256
TI  - Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin
      resistance.
AB  - Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one
      of the major signals that relay the status of fat stores to the hypothalamus and
      plays a significant role in energy homeostasis. Understanding the mechanisms of
      leptin signaling in the hypothalamus during normal and pathological conditions,
      such as obesity, has been the subject of intensive research during the last
      decade. It is now established that leptin action in the hypothalamus in
      regulation of food intake and body weight is mediated by a neural circuitry
      comprising of orexigenic and anorectic signals, including NPY, MCH, galanin,
      orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3
      pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role
      in leptin signaling in the hypothalamus. It is now established that central
      leptin resistance contributes to the development of diet-induced obesity and
      ageing associated obesity. Central leptin resistance also occurs due to
      hyperleptinimia produced by exogenous leptin infusion. A defective nutritional
      regulation of leptin receptor gene expression and reduced STAT3 signaling may be
      involved in the development of leptin resistance in DIO. However, leptin
      resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3
      pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway,
      defects in other leptin signaling pathways may be involved in leptin resistance.
      We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of
      the mechanisms behind the development of central leptin resistance seen in
      obesity.

PMID- 14726257
TI  - G-protein coupled receptor oligomerization in neuroendocrine pathways.
AB  - Protein-protein interactions are fundamental processes for many biological
      systems including those involving the superfamily of G-protein coupled receptors
      (GPCRs). A growing body of biochemical and functional evidence supports the
      existence of GPCR-GPCR homo- and hetero-oligomers. In particular, hetero
      oligomers can display pharmacological and functional properties distinct from
      those of the homodimer or oligomer thus adding another level of complexity to how
      GPCRs are activated, signal and traffick in the cell. Dimerization may also play
      a role in influencing the activity of agonists and antagonists. We are only
      beginning to unravel how and why such complexes are formed, the functional
      implications of which will have an enormous impact on GPCR biology. Future
      research that studies GPCRs as dimeric or oligomeric complexes will enhance not
      only our understanding of GPCRs in cellular function but will also be critical
      for novel drug design and improved treatment of the vast array of GPCR-related
      conditions.

PMID- 14726258
TI  - The biology of gonadotropin hormone-releasing hormone: role in the control of
      tumor growth and progression in humans.
AB  - It is now well known that different forms of GnRH coexist in the same vertebrate
      species. In humans, two forms of GnRH have been identified so far. The first form
      corresponds to the hypophysiotropic decapeptide, and is now called GnRH-I. The
      second form has been initially identified in the chicken brain, and it is
      referred to as GnRH-II. GnRH-I binds to and activates specific receptors,
      belonging to the 7 transmembrane (7TM) domain superfamily, present on pituitary
      gonadotropes. These receptors (type I GnRH receptors) are coupled to the
      Gq/11/PLC intracellular signalling pathway. A receptor specific for GnRH-II (type
      II GnRH receptor) has been identified in non-mammalian vertebrates as well as in
      primates, but not yet in humans. In the last 10-15 years experimental evidence
      has been accumulated indicating that GnRH-I is expressed, together with its
      receptors, in tumors of the reproductive tract (prostate, breast, ovary, and
      endometrium). In these hormone-related tumors, activation of type I GnRH
      receptors consistently decreases cell proliferation, mainly by interfering with
      the mitogenic activity of stimulatory growth factors (e.g., EGF, IGF). Recent
      data seem to suggest that GnRH-I might also reduce the migratory and invasive
      capacity of cancer cells, possibly by affecting the expression and/or activity of
      cell adhesion molecules and of enzymes involved in the remodelling of the
      extracellular matrix. These observations point to GnRH-I as an autocrine negative
      regulatory factor on tumor growth progression and metastatization. Extensive
      research has been performed to clarify the molecular mechanisms underlying the
      peculiar antitumor activity of GnRH-I. Type I GnRH receptors in hormone-related
      tumors correspond to those present at the pituitary level in terms of cDNA
      nucleotide sequence and protein molecular weight, but do not share the same
      pharmacological profile in terms of binding affinity for the different synthetic
      GnRH-I analogs. Moreover, the classical intracellular signalling pathway
      mediating the stimulatory activity of the decapeptide on gonadotropin synthesis
      and secretion is not involved in its inhibitory activity on hormone-related tumor
      growth. In these tumors, type I GnRH receptors are coupled to the Gi-cAMP, rather
      than the Gq/11-PLC, signal transduction pathway. Recently, we have reported that
      GnRH-I and type I GnRH receptors are expressed also in tumors not related to the
      reproductive system, such as melanoma. Also in melanoma cells, GnRH-I behaves as
      a negative regulator of tumor growth and progression. Interestingly, the
      biochemical and pharmacological profiles of type I GnRH receptors in melanoma
      seem to correspond to those of the receptors at pituitary level. The data so far
      reported on the expression and on the possible functions of GnRH-II in humans are
      still scanty. The decapeptide has been identified, together with a 'putative'
      type II GnRH receptor, both in the central nervous system and in peripheral
      structures, such as tissues of the reproductive tract (both normal and tumoral).
      The specific biological functions of GnRH-II in humans are presently under
      investigation.

PMID- 14726259
TI  - MAM 2004. Molecular Approaches to Malaria. 1-5 February, Lorne, Australia.
      Abstracts.

PMID- 14726265
TI  - The debate about the antipsychotics.

PMID- 14726266
TI  - Hate crimes against gay males: an overview.
AB  - As the United States has become more multicultural and diverse, there has been an
      increase in violence motivated by hate. Hate crimes against gay males are the
      most prevalent of the hate crimes based on sexual orientation. Hate crimes have
      their roots in normative, individual, and societal attitudes and ideologies that
      lead to intimidation, bullying, teasing, physical assault, rape, and murder. This
      paper provides an overview of the issues specific to hate crime assaults against
      gay males. Mental health nurses may find this knowledge useful in developing
      further nursing inquiry, education, and clinical practice related to hate crime
      and violence prevention.

PMID- 14726267
TI  - Uxoricide: a phenomenological study of adult survivors.
AB  - The effect on children of the murder of a parent by the other parent, uxoricide,
      is immediate and devastating. Usually in a single act, the child loses both
      parents, one to death and the other to the criminal justice system. This is a
      report on a qualitative study, with a sample of seven adults, designed to explore
      the experiences of these children as they grow to adulthood. The major themes
      developed in the data analysis include (1) a surprising lack of anger regarding
      the perpetrator, (2) intimate abuse in later personal relationships, and (3) a
      beginning description of paths to recovery.

PMID- 14726268
TI  - Age and problem behaviors among adolescent multi-ethnic females.
AB  - Depression, alcohol use, and suicidal behaviors are common among adolescents.
      However, little is known if these problem behaviors differ among ethnically
      diverse females across the adolescent years. Using the National Longitudinal
      Study of Adolescent Health database, we conducted regression analyses to compare
      these problem behaviors in three age cohorts across five ethnic groups of
      adolescent females. The random sample (N = 3,297, aged 12-19 years) included
      Latinas, African-, Asian-, Native-, and Euro-American females. There are
      differences in these problem behaviors between some age cohorts across ethnic
      groups. Significance and implications of the results to mental health nursing
      research and practice are described.

PMID- 14726269
TI  - The inspiration of hope in bereavement counseling.
AB  - While most healthcare workers would agree that hope is necessary for healthy
      living, the current understanding of hope and hoping is incomplete. This article
      reports on a study that attempted to answer the question: Do bereavement
      counselors inspire hope in their clients, and if so, how? The study used a
      modified grounded theory method and collected data, by means of interviews, from
      a total sample of 12 participants, comprising bereavement counselors and ex
      clients who had received bereavement counseling. The data were coded and analysed
      using the constant comparative method, which produced an emerging, integrated,
      substantive grounded theory of hope inspiration for this client group. This
      theory includes a core variable: the implicit projection of hope and hopefulness;
      and three subcore variables: forging the connection and the relationship;
      facilitating a cathartic release; and experiencing a good (healthy) ending. The
      theory indicates that this hope inspiration appears to be a subtle, unobtrusive
      process that was bound up with the necessary and sufficient human qualities in
      the counselor and the projection of these into the environment (and client).

PMID- 14726270
TI  - Violent encounters in psychiatric care: a phenomenological study of embodied
      caring knowledge.
AB  - This article focuses on encounters that become violent, a problem in health care
      that has been the issue of many debates but is still not fully understood.
      Violent encounters refer to events where the patient expresses an aggressive and
      hostile attitude toward the caregiver. This study is part of a bigger project
      that aims to elucidate violent encounters from the caregivers' as well as the
      patients' perspectives. The purpose of this particular study was to describe the
      essence of violent encounters from the caregivers' perspective. Guided by a
      phenomenological method, data were analyzed within a reflective lifeworld
      approach. The essence of a violent encounter between caregivers and patients, as
      experienced by the caregivers, is a critical moment characterized by a tension
      between presence and distance, a moment where everything is happening at the same
      time. There are important meaning differences in relation to the violent
      encounter being viewed as positive rather than negative, based on the caregivers'
      ability to be present and their capacity in these trying situations to manage
      their fear. The findings also make explicit the particular knowledge that is
      needed for the caregiver to manage the threat of violence in a creative way.

PMID- 14726272
TI  - Cyclamate intake and cyclohexylamine excretion are not related to male fertility
      in humans.
AB  - Cyclamate and its metabolite cyclohexylamine affect male fertility in high dose
      animal studies, but this affect has not been investigated in epidemiological
      studies. This paper reports the first epidemiological study designed to
      investigate the possibility of a relationship between cyclamate and
      cyclohexylamine and male fertility in humans, in which 405 cases of clinically
      defined infertility in men and 379 controls were surveyed. Semen evaluation,
      urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were
      compared between cases and controls. No evidence was found of a significant
      association between cyclamate intake and male infertility; neither high cyclamate
      nor high cyclohexylamine excretion were associated with elevated risk. The lack
      of association remained after adjusting by age, area of residence, education,
      total energy intake and other variables. No significant correlations were
      observed between cyclamate intake, metabolism or excretion, and sperm count and
      motility. The results demonstrate no effect of cyclamate or cyclohexylamine on
      male fertility at the present levels of cyclamate consumption.

PMID- 14726273
TI  - Acrylamide in Asian foods in Hong Kong.
AB  - About 400 food samples, mainly Asian foods available in Hong Kong, were tested
      for acrylamide by an LC-MS/MS method using [1, 2, 3-(13)C(3)]-acrylamide as
      surrogate. The acrylamide levels in the more commonly consumed food items in the
      food groups such as rice and rice products, noodles, bakery and batter-based
      products, were generally less than 60 microg kg(-1). Higher levels were found in
      the food groups such as biscuit-related products and crisps. The highest levels
      were detected in potato crisps (1500-1700 microg kg(-1)). Lower levels were found
      in rye flour-based crisps (440 microg kg(-1)), followed by corn-based (65 to 230
      microg kg(-1)) and wheat flour-based crisps (61-200 microg kg(-1)), and then rice
      flour-based crisps (15-42 microg kg(-1)). The acrylamide formation during deep
      frying of a wheat flour-based product, Chinese fried fritter, was studied. Deep
      frying at 170 degrees C resulted in gentle but steady rise in acrylamide content.
      A steep rise for frying at 210 degrees C was recorded. The moisture content of
      the product decreased with frying time, but the fat content increased. It is
      proposed that the reaction for the formation of acrylamide was initiated on the
      surface and then penetrated into the interior of the food matrix by heat transfer
      via radiation/conduction and diffusion of hot oil.

PMID- 14726274
TI  - Survey of total mercury and methylmercury levels in edible fish from the Adriatic
      Sea.
AB  - Total mercury and methylmercury concentrations were measured in the muscle tissue
      of different fish species from the Adriatic Sea to ascertain whether the
      concentrations exceeded the maximum level fixed by the European Commission. Large
      species-dependent variability was observed. The highest total mercury mean
      concentrations were in benthic (0.20-0.76 microg g(-1) wet wt) and demersal fish
      (0.22-0.73 microg g(-1) wet wt), while pelagic species showed the lowest levels
      (0.09-0.23 microg g(-1) wet wt). In 15% of frost fish, in 42% of skate and in 30%
      of angler fish samples total mercury concentrations exceeded the maximum level
      fixed by the European Commission (Hg = 1 microg g(-1) wet wt); for the species
      for which the maximum level was set to 0.5 microg g(-1) wet wt, concentrations
      exceeding the prescribed legal limit were observed in 6.4% of bokkem, in 6.6% of
      pandora, in 20% of megrin, in 12.5% of four-spotted megrim, in 16% of striped
      mullet, in 5.0% of forkbeard and in 5.3% of picarel samples. In all the different
      species, mercury was present almost completely in the methylated form, with mean
      percentages between 70 and 100%. Weekly intake was estimated and compared with
      the provisional tolerable weekly intake recommended by the FAO/WHO Expert
      Committee on Food Additives. A high exposure was associated with the consumption
      of only skates, frost fish and angler fish, thought the consumption of the other
      species, such as, megrim, four spotted megrim, red fish striped mullet and
      forkbeard, resulted in a weekly intake slightly below the established provisional
      tolerable weekly intake.

PMID- 14726276
TI  - Incidence of microflora and of ochratoxin A in green coffee beans (Coffea
      arabica).
AB  - Coffee is produced in tropical countries around the Equator where climatic
      conditions are favourable for fungal development and mycotoxin production;
      however, mycotoxins do not only occur in the tropical countries. The aim was to
      evaluate the mycoflora and possible incidence of ochratoxin A (OTA) in 60 samples
      of green coffee beans from Brazil. The mycological evaluation was carried out
      using a conventional method and the OTA was determined using sequential phenyl
      silane and immunoaffinity column cleanup followed by HPLC. The detection limit
      was 0.2 microg kg(-1). Practically all samples (91.7%) were contaminated with
      moulds. The dominant fungal genus was Aspergillus, including A. niger (83.3%), A.
      ochraceus (53.3%) and A. flavus (25.0%). The occurrence and the levels of the
      genus Cladosporium (16.6%) and Penicillium (10.0%) were substantially lower than
      Aspergilli. Twenty samples (33.3%) of 60 were contaminated with the toxin at
      levels ranging from 0.2 to 7.3microg kg(-1). The average concentration was 2.38
      microg kg(-1). All positive samples showed OTA levels below the limit suggested
      by the European Union (8 microg kg(-1)).

PMID- 14726275
TI  - Mycological survey for potential aflatoxin and ochratoxin producers and their
      toxicological properties in harvested Brazilian black pepper.
AB  - A mycological survey was carried out on 115 samples of whole dried black pepper
      seeds, from two main production regions of Brazil (Para and Espirito Santo). A
      high incidence of contamination was verified in both regions when 99.1% of the
      samples showed filamentous fungi contamination. A total of 497 species of nine
      different genera were isolated (Aspergillus, Eurotium, Rhizopus, Penicillium,
      Curvularia, Cladosporium, Absidia, Emericella and Paecilomyces). The genus
      Aspergillus was the predominant (53.5%) followed by species from the Eurotium
      genus (24.5%). Eurotium chevalieri (16.4%) was the most predominant species
      followed by A. flavus (14.6%) present on 55 samples of black pepper (47.8%)
      analysed. Twenty-five samples (21.7%) were contaminated with aflatoxigenic
      strains of A. flavus and A. parasiticus. In relation to the types of aflatoxins
      produced by mycotoxigenic strains, it was observed that 25 strains (44.6%) of 56
      isolated of A. flavus produced aflatoxins. From 12 samples, A. ochraceus species
      were isolated in low frequency (3.5%). Two strains of A. ochraceus from 16
      isolated were producers of ochratoxin A. With respect to the aflatoxins and
      ochratoxin A natural contamination, none of the samples presented detectable
      levels of these mycotoxins using thin-layer chromatographic analysis.

PMID- 14726277
TI  - Effects of heating procedures on deoxynivalenol, nivalenol and zearalenone levels
      in naturally contaminated barley and wheat.
AB  - The influence of heating temperature and time on deoxynivalenol (DON), nivalenol
      (NIV) and zearalenone (ZEA) contents in naturally co-contaminated barley and
      wheat was investigated intending to establish the basis for a decontamination
      model of Fusarium mycotoxins in cereals. The standard toxins and whole barley
      powder samples were heated in a convection oven at 140, 160, 180, 200, or 220
      degrees C, and kernel subsamples (200 g each) were roasted in an experimental
      rotary gas-fired roaster at 150, 180 or 220 degrees C. All treatments resulted in
      a time-temperature-dependent decomposition of the toxins; the logarithm of the
      toxin remaining % presented a linear relationship with heating time. The lines
      equations were used to estimate the half (H) and decimal (D) decomposition times
      (time required to destroy 50 or 90% of the toxin, respectively). DON and NIV H
      and D decomposition times were similar and 50% shorter for heated standards than
      for whole barley powder. ZEA standard values were considerably longer, while
      whole barley powder values were comparable with those of DON and NIV. At 220
      degrees C, D decomposition times of DON, NIV and ZEA heated standards were 11, 10
      and 85 min, respectively, while the values obtained in whole barley powder were
      the same for the three toxins (25 min). The determination of H and D
      decomposition values constitutes a basis to understand the heating stability
      nature of each toxin.

PMID- 14726278
TI  - Zearalenone in maize: stability testing and matrix characterisation of a
      certified reference material.
AB  - Within the certification process of a reference material for the determination of
      the mycotoxin zearalenone (ZON) in maize, short- and long-time stability tests of
      naturally contaminated maize have been performed. The short-term stability of ZON
      in the maize was evaluated under four different conditions (4, 25, 40 and 70
      degrees C) in preliminary studies. Four storage times of 0, 1, 2 and 4 weeks were
      investigated using HPLC. The long-term stability study was conducted with
      measurements after 0, 3, 6, 12, 24 and 36 months under three storage conditions
      (4, 25 and 40 degrees C) in preliminary studies using HPLC. Stability data gained
      under two different conditions (4 and 25 degrees C) with five storage times of 0,
      1, 6, 12 and 18 months were further evaluated for the contaminated maize in the
      certification process. Before the certification, the maize matrix had been
      characterized with respect to dry residue, ash content, fat content, protein
      content, ergosterol content and total dietary fibre, and the efficiency of gamma
      irradiation on the fungal flora was investigated. The stability of the maize
      matrix was evaluated by monitoring UV absorption and ergosterol content under
      four different storage conditions (4, 25, 35 and 70 degrees C) with five storage
      times of 0, 1, 6, 12 and 24 months. Other possibly occurring mycotoxins
      (deoxynivalenol, nivalenol, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol,
      fusarenon X and moniliformin) have been quantified. On the basis of the stability
      measurements, which showed no significant trends for both short- and long-term
      stabilities, it can be recommended to store the samples at temperatures < 4
      degrees C and ship the samples at ambient temperatures.

PMID- 14726279
TI  - Fate of ochratoxin A in the processing of whole wheat grains during milling and
      bread production.
AB  - Batches of whole wheat contaminated with ochratoxin A were produced by
      inoculation with Penicillium verrucosum under controlled conditions in the
      laboratory. The fate of ochratoxin was followed through initial cleaning,
      abrasive scouring of the outer grain coat, milling into wholemeal wheat or into
      10 milled fractions. Bread was baked from both wholemeal flour and straight-run
      white flour. Concentrations of ochratoxin A in the cleanings, scourings, and the
      bran and offal fractions were increased, but reduced in the white flour. Scouring
      removed up to 44% of the ochratoxin A present, but only a small further loss
      occurred in the bread-making process. An overall reduction of about 75% could be
      achieved in white bread using a combination of cleaning scouring and removal of
      the bran and offal fractions. Maximum overall reduction in producing wholemeal
      bread was about 40%. The reduction in ochratoxin A that can be achieved must be
      considered in relation to economic constraints concerning the disposal of wasted
      grain. Appropriate strategies for the use or disposal of potentially highly
      contaminated cleanings, scourings, bran or offal must be established.

PMID- 14726280
TI  - Determination of benzo(a)pyrene by GC/MS/MS in retail olive oil samples available
      in Qatar.
AB  - A survey was carried out for the presence of benzo(a)pyrene (B(a)P) in olive oils
      following reports that some batches of Spanish olive-pomace oil and its products
      contained high levels of B(a)P. Three types of olive oils (1) virgin olive oil,
      (2) refined olive oil and (3) olive-pomace oil, originating from France, Greece,
      Italy, the Lebanon, Spain, Tunisia and Turkey, and available on Qatar market,
      were analysed for B(a)P. Determination was carried out by extraction from a
      cyclohexane solution with N,N-dimethylformamide: water (9:1), back extraction
      with cyclohexane, followed by clean-up on a silica gel column and quantification
      by GC/MS/MS. The recovery and limit of quantitation of B(a)P in olive oils by
      this method were estimated as 88% and 0.5 microg kg(-1), respectively. B(a)P was
      detected in amounts below the permitted level of 2 microg kg(-1) in all 31 virgin
      olive oil samples and in 13 refined olive oil samples. However, all seven samples
      of Spanish olive-pomace oil produced and packed in Spain and three samples of
      olive-pomace oil produced in Spain, but packed in Saudi Arabia, were found to be
      contaminated with B(a)P, the level ranging from 3.1 to 70.8 microg kg(-1). In two
      samples of olive-pomace oil originating from Greece, B(a)P was not detected.

PMID- 14726281
TI  - Aldehyde contamination of mineral water stored in PET bottles.
AB  - Aldehyde contaminations that might accompany production of mineral water stored
      in PET bottles were investigated. One of the production lines of carbonated
      mineral water in Poland was monitored and PET bottles commonly used for mineral
      water storage were evaluated. Formaldehyde and acetaldehyde were the most
      important carbonyls identified in series of bottled water samples, but also
      propanal, nonanal and glyoxal were found in water samples from the production
      line. Aldehydes are present everywhere in the environment and can be determined
      even in pure water at low microg l(-1) levels. It was observed that the
      concentration of acetaldehyde in water stored in PET bottles depended mainly on
      the concentration of acetaldehyde in PET material and could reach more than 200
      microg l(-1). The temperature, time of storage and concentration of carbon
      dioxide gas contribute to the migration of aldehydes from bottle walls to mineral
      water. Higher pressure of the carbonated waters and not CO(2) itself or lower pH
      of waters seems responsible for higher concentration of acetaldehyde.

PMID- 14726282
TI  - Migration of 2-butoxyethyl acetate from polycarbonate infant feeding bottles.
AB  - An enforcement campaign was carried out to assess the migration of 2-butoxyethyl
      acetate (2-BEA) from polycarbonate infant feeding bottles intended for repeated
      use. Migration was measured by three successive migration tests into two of the
      European Union official food simulants: distilled water and 3% acetic acid
      testing at 40 degrees C for 10 days. The Danish Veterinary and Food
      Administration (DVFA) has assessed that a migration above 0.33 mg for 2-BEA and a
      group of eight related substances kg(-1) foodstuff from plastics articles used
      exclusively for infants is unacceptable. Migration of 2-BEA was found from eight
      of 12 bottles. However, migration above the target value of 0.33 mg kg(-1) was
      not observed in the third decisive test from any of the 12 different brands of
      polycarbonate feeding bottles. A migration of between 0.05 and 0.26 mg kg(-1)
      from seven of 12 bottles was measured to 3% acetic acid in the third test,
      whereas no migration to distilled water was observed in the third test. The
      average recovery of 2-BEA after the 10-day exposure at the target value of 0.33
      mg kg(-1) was 77% into distilled water and 36% into 3% acetic acid. The limited
      recovery was understandable as 2-BEA was partly hydrolysed in the aqueous food
      simulants and 2-butoxyethanol, a hydrolysis product and one of the related
      substances was identified. Quantification was carried out using gas
      chromatography after liquid/liquid extraction of the food simulant.

PMID- 14726283
TI  - Acute predictors of real-world outcomes following traumatic brain injury: a
      prospective study.
AB  - PRIMARY OBJECTIVE: To determine whether the recovery of acute attention and
      memory improves the prediction of real-world outcomes over that provided by
      standard demographic and injury-severity measures. RESEARCH DESIGN: Participants
      were recruited consecutively at the time of injury and followed prospectively at
      1 (time 1, or T1) and 4 years (time 2, or T2). METHODS AND PROCEDURES: Measures
      of attention and memory and the Galveston Orientation and Amnesia Test (GOAT)
      were administered to 94 participants daily from the time of injury until the
      criterion was met. Sixty-three per cent returned at T1 and 53% returned at T2.
      Outcomes were psychosocial distress, return to work and/or school, and quality of
      life. MAIN OUTCOMES AND RESULTS: Recovery of attention, memory and orientation
      did not significantly improve prediction of outcomes at T1, but did so at T2. At
      T2, recovery of free recall of three words over 24 h was a more sensitive
      predictor of psychosocial distress and return to productivity than the GOAT.
      CONCLUSIONS: Free recall of three words may be a useful acute clinical test to
      enhance prediction of long-term outcomes.

PMID- 14726284
TI  - Parental coping following childhood acquired brain injury.
AB  - PRIMARY OBJECTIVE: To examine parental coping following an acquired brain injury
      of their child, the relationship between maternal and paternal coping, and the
      extent to which social support and family environment affect parental coping.
      RESEARCH DESIGN: A cross-sectional design was used. METHODS AND PROCEDURES:
      Parents (n = 30) of children with acquired brain injury provided relevant
      demographic data and completed questionnaires investigating coping, social
      support and perceptions of family environment. MAIN OUTCOMES AND RESULTS:
      Perception-focused coping strategies were used most often by parents. Mothers had
      a more extensive repertoire than fathers, and the relationship between maternal
      and paternal coping appeared to be complementary. Relationships were found
      between emotion-focused coping and instrumental support (r = 0.39) and perception
      focused coping and family cohesion (r = 0.37). CONCLUSIONS: Recognizing parental
      coping styles, enhancing the development of positive strategies, and underscoring
      the importance of social support and the family environment will assist parents
      to cope positively with their child's acquired brain injury.

PMID- 14726285
TI  - Attentional control and slowness of information processing after severe traumatic
      brain injury.
AB  - Attention is a basic cognitive function and a prerequisite for other cognitive
      processes and is frequently impaired after traumatic brain injury. In the present
      study, 29 severe traumatic brain injury patients and 30 control subjects
      completed a battery of three neuropsychological tests of attention (WCST, TMT,
      Stroop). The aim was to clarify the attentional mechanisms underlying tests
      performance and to explore the types of attentional impairment after severe
      traumatic brain injury. Significant differences were found between the control
      and clinical groups in almost all measures. However, some of these differences
      disappeared when the speed of information processing was controlled using
      covariance analysis. In addition, a factor analysis revealed a four-factor
      solution explaining 89.6% of the variance in the data, i.e. cognitive
      flexibility, speed of processing, interference and working memory. This result
      supports the view of at least four different subprocesses of attentional control
      underlie test performance and allows one to differentiate between high- and low
      level processes. The implications for neuropsychological assessment and
      rehabilitation are discussed.

PMID- 14726286
TI  - Language and memory profiles of adolescents with traumatic brain injury.
AB  - The performance of adolescents who suffered a traumatic brain injury in
      childhood, on language comprehension tasks with varying working memory demands,
      was examined. It was hypothesized that adolescents with a traumatic brain injury
      would perform more poorly than their non-injured peers, particularly on those
      tasks with high working memory demands. A case study design allowed for both
      group and intra-participant comparisons. A battery of language comprehension and
      working memory tasks was administered to six adolescents aged 12-16 years. Their
      performance was compared with six individually age-matched peers with typical
      development and to the normative data of the standardized tests. Intra
      participant performance was examined by comparing results across language tasks
      that varied in working memory demands. Analysis revealed that individuals with
      traumatic brain injury performed poorly compared with their age-matched peers.
      However, the pattern of listening comprehension impairment differed across
      individuals and marked variability within the comprehension profiles for some
      individuals with traumatic brain injury was evident. Language comprehension tasks
      with high working memory demands generally posed the most difficulty for
      individuals with traumatic brain injury.

PMID- 14726287
TI  - Do somatosensory evoked potentials in traumatic brain injury patients indicate
      brainstem generators for frontally recorded N18, P20 and cervical N13?
AB  - PRIMARY OBJECTIVE: To examine the generator of frontal somatosensory evoked
      potentials by studying patients with traumatic brain injury in the chronic phase.
      RESEARCH DESIGN: A prospective, non-comparative case series. METHODS AND
      PROCEDURES: Median nerve somatosensory evoked potentials were performed in 26
      survivors of severe traumatic brain injury, which had taken place at a mean of 7
      months before. Potentials of short latency somatosensory evoked potentials were
      recorded simultaneously over the frontal and parietal scalp. MAIN OUTCOMES AND
      RESULTS: Frontally recorded latencies N18, P20 and N13 recorded from C2
      correlated highly significantly with the duration of coma (p<0.01), a history of
      raised intracranial pressure (p<0.05) and with each other (p<0.01) in traumatic
      brain injury patients. CONCLUSIONS: These findings indicate that frontally
      recorded N18, P20 and N13 recorded from C2 are generated in part in the
      brainstem, which becomes damaged by increased intracranial pressure due to
      secondary injury in severe traumatic brain injury.

PMID- 14726288
TI  - Sexually intrusive behaviour following brain injury: approaches to assessment and
      rehabilitation.
AB  - Sexually intrusive behaviour, which may range from inappropriate commentary to
      rape, is often observed following a traumatic brain injury. It may represent
      novel behaviour patterns or an exacerbation of pre-injury personality traits,
      attitudes, and tendencies. Sexually intrusive behaviour poses a risk to staff and
      residents of residential facilities and to the community at large, and the
      development of a sound assessment and treatment plan for sexually intrusive
      behaviour is therefore very important. A comprehensive evaluation is best served
      by drawing on the fields of neuropsychology, forensic psychology, and cognitive
      rehabilitation. The paper discusses the types of brain damage that commonly lead
      to sexually intrusive behaviour, provides guidance for its assessment, and
      presents a three-stage treatment model. The importance of a multidisciplinary
      approach to both assessment and treatment is emphasized. Finally, a case example
      is provided to illustrate the problem and the possibilities for successful
      management.

PMID- 14726289
TI  - Post-traumatic bilateral facial palsy: a case report and literature review.
AB  - Bilateral facial paralysis due to basilar skull fracture involving the temporal
      bone is rare and, unlike unilateral facial palsy, it can be difficult to
      recognize because of a lack of facial asymmetry. Thorough clinical history and
      physical exam, high-resolution CT scan and electrodiagnostic tests can help to
      make the diagnosis of bilateral facial nerve palsy and early detection,
      evaluation and intervention may be important for optimal functional recovery. A
      16-year-old male sustained closed head injury after motor vehicle collision. The
      initial head CT scan showed bilateral temporal bone fractures. On admission to
      the neurotrauma intensive care unit, his Glasgow Coma Score was 9T. On post
      injury day 4, the patient was noted to have incomplete closure of both eyes and 3
      days later he had difficulty with bilateral facial muscle movement during a
      feeding trial. Electrodiagnostic testing confirmed the diagnosis of bilateral
      facial nerve injury without evidence of significant distal axonal degeneration. A
      high-resolution CT scan showed bilateral temporal bone fractures without
      involvement of the fallopian canals. There was no surgical intervention based on
      the high-resolution CT scan and the delayed onset of facial palsy. A short course
      of prednisone was administered. By 10 months, the patient showed nearly complete
      recovery of his bilateral facial nerve function. Early detection, evaluation and
      intervention are important for optimal functional recovery after facial nerve
      injury. When the temporal bone is fractured, high suspicion for facial nerve
      injury, either unilateral or bilateral, is warranted.

PMID- 14726290
TI  - Diagnostic ambiguities in a case of post-traumatic narcolepsy with cataplexy.
AB  - Narcolepsy arising from trauma can present particular problems of differential
      diagnosis. In this case study presentation the patient suffered a head trauma,
      without unconsciousness, and began to experience unusual episodic behaviours.
      Symptom presentation differed from the typical clinical manifestations of
      idiopathic narcolepsy leading to an 8-year search for a definitive diagnosis. Key
      relevant aspects that led to diagnostic ambiguities were the order of symptom
      development, negative for the antigen HLA DR2, significance of the Multiple Sleep
      Latency Test (MSLT) mean sleep latency versus number of sleep onset rapid eye
      movement periods, the somewhat atypical features of cataplexy, the coexistence of
      sleep apnoea, and the mildness of the original head injury. It is argued that
      cases of post-traumatic narcolepsy should be considered in the context of their
      clinical development over time and that practitioners should be aware that this
      form of narcolepsy can differ from the typical clinical history of idiopathic
      narcolepsy.

PMID- 14726294
TI  - Proceedings of the Facial and Aesthetics Conference and Exhibition. Royal College
      of Physicians, London, 14th-15th June, 2003.

PMID- 14726295
TI  - Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats.
AB  - 5-Lipoxygenase (5-LO) and its downstream leukotriene products have been
      implicated in the development of pulmonary hypertension. In this study, we
      examined the effects of 5-LO overexpression in rat lungs on pulmonary
      hypertension using a recombinant adenovirus expressing 5-LO (Ad5-LO).
      Transthoracic echocardiography and right heart catheterization data showed that 5
      LO overexpression in the lung did not cause pulmonary hypertension in normal
      rats; however, it markedly accelerated the progression of pulmonary hypertension
      in rats treated with monocrotaline (MCT). An increase in pulmonary artery
      pressure occurred earlier in the rats treated with MCT + Ad5-LO (7-10 days)
      compared with those treated with control vector, MCT + adenovirus expressing
      green fluorescent protein (AdGFP), or MCT alone (15-18 days). The weight ratio of
      the right ventricle to left ventricle plus septum was higher in the MCT + Ad5-LO
      group than that of the MCT + AdGFP or MCT group (0.45 +/- 0.08 vs. 0.35 +/- 0.03
      or 0.33 +/- 0.06). Lung tissue histological sections from MCT + Ad5-LO rats
      exhibited more severe inflammatory cell infiltration and pulmonary vascular
      muscularization than those from MCT + AdGFP- or MCT-treated rats. Administration
      of 5-LO inhibitors, zileuton or MK-886, to either MCT- or MCT + Ad5-LO-treated
      rats prevented the development of pulmonary hypertension. These data suggest that
      5-LO plays a critical role in the progression of pulmonary hypertension in rats
      and that the detrimental effect of 5-LO is manifest only in the setting of
      pulmonary vascular endothelial cell dysfunction.

PMID- 14726297
TI  - Physical training and heart rate and blood pressure variability: a 5-yr
      randomized trial.
AB  - We studied the effect of regular physical activity on cardiac and vascular
      autonomic modulation during a 5-yr controlled randomized training intervention in
      a representative sample of older Finnish men. Heart rate variability (HRV) and
      blood pressure variability (BPV) are markers of cardiac and vascular health,
      reflecting cardiac and vascular autonomic modulation. One hundred and forty
      randomly selected 53- to 63-yr-old men were randomized into two identical groups:
      an intervention (EX) group and a reference (CO) group, of which 89 men remained
      until the final analysis (EX: n = 47; CO: n = 42). The EX group trained for 30-60
      min three to five times a week with an intensity of 40-60% of maximal oxygen
      consumption. The mean weekly energy expenditure of the training program for the 5
      yr training period was 3.80 MJ, and 71% of the EX group exceeded the mean. The EX
      group had a significantly (P < 0.01) higher oxygen consumption at ventilatory
      aerobic threshold (VO2VT) than the CO group at the 5-yr time point. VO2VT had a
      tendency to increase in the EX group and decrease in the CO group (interaction P
      < 0.001) from the baseline to the 5-yr time point. Peak performance did not
      change. Low-frequency power of R-R interval variability decreased in the EX group
      (P < 0.01, by 6%) from the baseline to the 5-yr time point. BPV did not change.
      In conclusion, low-intensity regular exercise training did not prevent HRV from
      decreasing or change BPV in 5 yr in older Finnish men.

PMID- 14726296
TI  - Inhibition of PKC phosphorylation of cTnI improves cardiac performance in vivo.
AB  - Protein kinase C (PKC) modulates cardiomyocyte function by phosphorylation of
      intracellular targets including myofilament proteins. Data generated from studies
      on in vitro heart preparations indicate that PKC phosphorylation of troponin I
      (TnI), primarily via PKC-epsilon, may slow the rates of cardiac contraction and
      relaxation (+dP/dt and -dP/dt). To explore this issue in vivo, we employed
      transgenic mice [mutant TnI (mTnI) mice] in which the major PKC phosphorylation
      sites on cardiac TnI were mutated by alanine substitutions for Ser(43) and
      Ser(45) and studied in situ hemodynamics at baseline and increased inotropy.
      Hearts from mTnI mice exhibited increased contractility, as shown by a 30%
      greater +dP/dt and 18% greater -dP/dt than FVB hearts, and had a negligible
      response to isoproterenol compared with FVB mice, in which +dP/dt increased by
      33% and -dP/dt increased by 26%. Treatment with phenylephrine and propranolol
      gave a similar result; FVB mouse hearts demonstrated a 20% increase in developed
      pressure, whereas mTnI mice showed no response. Back phosphorylation of TnI from
      mTnI hearts demonstrated that the mutation of the PKC sites was associated with
      an enhanced PKA-dependent phosphorylation independent of a change in basal cAMP
      levels. Our results demonstrate the important role that PKC-dependent
      phosphorylation of TnI has on the modulation of cardiac function under basal as
      well as augmented states and indicate interdependence of the phosphorylation
      sites of TnI in hearts beating in situ.

PMID- 14726298
TI  - Virtual electrode theory explains pacing threshold increase caused by cardiac
      tissue damage.
AB  - The virtual electrode polarization (VEP) effect is believed to play a key role in
      electrical stimulation of heart muscle. However, under certain conditions,
      including clinically, its existence and importance remain unknown. We
      investigated the influence of acute tissue damage produced by continuous pacing
      with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min)
      on stimulus-generated VEPs and pacing thresholds. A fluorescent optical mapping
      technique was used to obtain stimulus-induced transmembrane potential
      distribution around a pacing electrode applied to the ventricular surface of a
      Langendorff-perfused rabbit heart (n = 5). Maps and pacing thresholds were
      recorded before and after tissue damage. Spatial extents of electroporation and
      cell uncoupling were assessed by propidium iodide (n = 2) and connexin43 (n = 3)
      antibody staining, respectively. On the basis of these data, passive and active
      three-dimensional bidomain models were built to determine VEP patterns and
      thresholds for different-sized areas of the damaged region. Electrophysiological
      results showed that acute tissue damage led to disappearance of the VEP with an
      associated significant increase in pacing thresholds. Damage was expressed in
      electroporation and cell uncoupling within an approximately 1.0-mm-diameter area
      around the tip of the electrode. According to computer simulations, cell
      uncoupling, rather than electroporation, might be the direct cause of VEP
      elimination and threshold increase, which was nonlinearly dependent on the size
      of the damaged region. Fiber rotation with depth did not substantially affect the
      numerical results. The study explains failure to stimulate damaged tissue within
      the concepts of the VEP theory.

PMID- 14726299
TI  - Dobutamine-tagged MRI for inotropic reserve assessment in severe CAD:
      relationship with PET findings.
AB  - The impact of blood flow reductions on the intramyocardial inotropic reserve has
      not yet been established in coronary artery disease (CAD). We therefore evaluated
      in severe CAD the relationship between positron emission tomography (PET)
      patterns of perfusion and glucose uptake and the corresponding tagged magnetic
      resonance imaging (tagged MRI) values of midmyocardial strains under low-dose
      dobutamine. Eighteen patients underwent tagged MRI (at rest, with dobutamine) and
      H2(15)O/18F-fluorodeoxyglucose PET. Regional midmyocardial circumferential
      shortening (Ecc) and PET patterns (normal, match viable, mismatch viable, and
      infarcted) were assessed in three tagged MRI/PET short-axis slices. Regional Ecc
      at rest correlated with both perfusion (r = 0.49) and glucose uptake (r = 0.58).
      The presence of the inotropic reserve was similar in normal, match viable, and
      infarcted (approximately 40% of regions vs. 52% in mismatch viable, P < 0.05),
      but the extent of the increase after dobutamine was lower in infarcted regions (P
      = 0.06). Within each PET pattern, regions were grouped according to their Ecc
      values at rest into three categories (high, intermediate, and low contractile
      performance). In mismatch viable (hibernation), the inotropic reserve was similar
      among the three categories, but in the other PET patterns the presence and extent
      of the inotropic reserve was higher in those regions with lowest Ecc (without
      significant differences in perfusion). In severe CAD, the presence of the
      inotropic reserve assessed by midmyocardial changes under dobutamine does not
      relate to resting perfusion. At a similar level of perfusion, the presence of the
      inotropic reserve is inversely related to contractile performance at rest, but
      our results suggest that it may not be true for hibernating myocardium.

PMID- 14726300
TI  - Infarction alters both the distribution and noradrenergic properties of cardiac
      sympathetic neurons.
AB  - Regional changes occur in the sympathetic innervation of the heart after
      myocardial infarction (MI), including loss of norepinephrine (NE) uptake and
      depletion of neuronal NE. This apparent denervation is accompanied by increased
      cardiac NE spillover. One potential explanation for these apparently
      contradictory findings is that the sympathetic neurons innervating the heart are
      exposed to environmental stimuli that alter neuronal function. To understand the
      changes that occur in the innervation of the heart after MI, immunohistochemical,
      biochemical, and molecular analyses were carried out in the heart and stellate
      ganglia of control and MI rats. Immunohistochemistry with panneuronal markers
      revealed extensive denervation in the left ventricle (LV) below the infarct, but
      sympathetic nerve fibers were retained in the base of the heart. Western blot
      analysis revealed that tyrosine hydroxylase (TH) expression (normalized to a
      panneuronal marker) was increased significantly in the base of the heart and in
      the stellate ganglia but decreased in the LV below the MI. NE transporter (NET)
      binding sites, normalized to total protein, were unchanged, except in the LV,
      where [3H]nisoxetine binding was decreased. TH mRNA was increased significantly
      in the left and right stellate ganglia after MI, while NET mRNA was not. In the
      base of the heart, increased TH coupled with no change in NET may explain the
      increase in extracellular NE observed after MI. Coupled with substantial
      denervation in the LV, these changes likely contribute to the onset of cardiac
      arrhythmias.

PMID- 14726301
TI  - Glutathione S-transferase overexpression protects against anthracycline-induced
      H9C2 cell death.
AB  - Anthracyclines (AC) are antitumor antibiotics with significant activity against
      solid and hematologic malignancies. One problem preventing more widespread use
      has been the development of cardiac toxicity. Experimental evidence supports
      oxidant stress as an important trigger and/or mediator of AC-induced
      cardiotoxicity (ACT). Therefore, reducing oxidant stress should be protective
      against ACT. To determine whether antioxidant protein overexpression can reduce
      ACT, we developed a cell culture model system using the H9C2 cardiac cell line
      exhibiting controlled overexpression of the alpha(4)-isoform of glutathione-S
      transferase (GST). Treatment with the AC doxorubicin (DOX) produced both oncosis,
      manifested by an increase in the number of cells staining positive for Trypan
      blue, and apoptosis, indicated by the presence of positive terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In
      both cases, the loss of cell viability was preceded by an AC-induced increase in
      fluorescence with carboxy-2',7'-dichlorofluorescein diacetate, demonstrating the
      presence of high levels of reactive oxygen species (ROS). The DOX-induced
      increase in ROS was reduced to control levels by maximal GST overexpression.
      Coincident with this elimination of oxidative stress, there was a reduction in
      both Trypan blue and TUNEL-positive cells, indicating that GST overexpression
      reduced both ROS and cell death in this model system. We conclude that GST
      overexpression may be an important part of a protective strategy against ACT and
      that this model system will aid in defining steps in the pathway(s) leading to AC
      induced cell death that can be therapeutically manipulated.

PMID- 14726302
TI  - Acute effects of testosterone on intracellular Ca2+ kinetics in rat coronary
      endothelial cells are exerted via aromatization to estrogens.
AB  - The objective of this work was to evaluate the effects of testosterone (T) and
      17beta-estradiol (E(2)) on coronary microvascular endothelial cells (CMECs) of
      male and female rats. To analyze the short-term effects of such sex steroid
      hormones on intracellular Ca(2+) concentration ([Ca(2+)](i)) kinetics, we used
      the chelating agent fura-2 acetoxymethyl ester. We also explored the possibility
      of testosterone aromatization by using selective inhibitors of the aromatase
      enzyme cytochrome P-450 aromatase (P450(arom)), aminoglutethimide (4 microM), and
      4-hydroxyandrostenedione (4 microM). The presence of P450(arom) was investigated
      by immunocytochemical and immunoblot assays using peptide-generated polyclonal
      antibodies raised against a 20-amino acid synthetic fragment of rat P450(arom)
      and by in situ hybridization to locate the aromatase mRNA in such cells. The
      activity of P450(arom) was demonstrated by the stereospecific loss of the tritium
      atom of [1beta-(3)H]androstenedione. Our results indicate that both T and E(2)
      induced a rapid increase in [Ca(2+)](i). The fact that the effects of E(2) and T
      were carried out within milliseconds suggests that they were exerted at the
      membrane level and not through intracellular receptors. The possibility of
      involvement of PLC-beta in these effects is suggested because U-73122 (a PLC
      inhibitor) blocked the effects of both T and E(2). Immunocytochemical assays
      indicated the expression of androgenic and estrogenic receptors in these cells.
      The effects of T were blocked by the selective aromatase inhibitors. We also
      demonstrated membrane association of P450(arom), expression of the ovary-specific
      mRNA after in situ hybridization, and E(2) formation resulting from a significant
      activity of P450(arom) in CMECs. There were no gender-based differences.

PMID- 14726303
TI  - Systemic responses to prolonged hemorrhagic hypotension.
AB  - Studies are needed to provide a rigorous examination of the relevance of
      monitored variables during prolonged hemorrhagic hypotension (HH). This study was
      designed to investigate the parameters that describe biochemical and O2 transport
      patterns in animals subjected to HH. Systemic parameters that could differentiate
      survivors from nonsurvivors were identified. An aortic flow probe was implanted
      in rats (n = 21) for continuous measurement of cardiac output. Experiments were
      performed 6-9 days after surgery. Rats were bled to a mean arterial pressure of
      40 mmHg and kept at that level using Ringer-lactate solution. Arterial and venous
      blood pressures, gases, acid-base status, glucose, lactate, electrolytes,
      hemoglobin, O2 saturation, heart and respiratory rates, total peripheral
      resistance, and O2 delivery and consumption were measured before hemorrhage, soon
      after 40 mmHg was reached, and 0.5, 1, 2, 3, and 4 h later. Fifty-three percent
      of rats survived > or =3 h (survivors); others were considered nonsurvivors.
      Nonsurvivors showed a significantly greater degree of metabolic acidosis than
      survivors. Arterial PO2, respiratory rate, O2 saturation, O2 content, glucose,
      and pH were significantly higher in survivors. The rate of Ringer-lactate
      infusion, arterial K+, and PCO2 were lower in survivors. Arterial K+ and
      respiratory rate were the only parameters significantly different between
      survivors and nonsurvivors at all time points during HH. Arterial levels of K+
      showed the clearest distinction between survivors and nonsurvivors and may
      explain the sudden death experienced by animals during HH. The data suggest that
      early respiratory and metabolic compensations are essential for survival of
      prolonged HH.

PMID- 14726304
TI  - Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI
      tagging: early onset and late peak of shortening in lateral wall.
AB  - Mechanical asynchrony is an important parameter in predicting the response to
      cardiac resynchronization therapy, but detailed knowledge of cardiac contraction
      timing in healthy persons is scarce. In this work, timing of cardiac contraction
      was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI
      myocardial tagging and strain analysis. Both the onset time of circumferential
      shortening (T(onset)) in early systole and the time of peak circumferential
      shortening (T(peak)) at end systole were determined. The onset of shortening
      width (time needed for 20-90% of the left ventricle to start shortening) was
      small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with
      earliest onset in the lateral wall and latest onset in the septum (P = 0.001).
      Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an
      opposite spatial pattern, with peak shortening occurring earlier in the septum
      than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than
      aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments,
      mainly in the lateral and basal segments. Shortening in these segments continued
      58 +/- 14 ms after aortic valve closure, during which circumferential shortening
      increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction
      in normal subjects may serve as a reference in detecting mechanical asynchrony
      due to intraventricular conduction defects or ischemia.

PMID- 14726305
TI  - Onset of pulsatile pressure causes transiently increased filtration through
      artery wall.
AB  - Convective fluid motion through artery walls aids in the transvascular transport
      of macromolecules. Although many measurements of convective filtration have been
      reported, they were all obtained under constant transmural pressure. However,
      arterial pressure in vivo is pulsatile. Therefore, experiments were designed to
      compare filtration under steady and pulsatile pressure conditions. Rabbit carotid
      arteries were cannulated and excised from male New Zealand White rabbits
      anesthetized with pentobarbitol sodium (30 mg/kg i.v. administered). Hydraulic
      conductance was measured in cannulated excised rabbit carotid arteries at steady
      pressure. Next, pulsatile pressure trains were applied within the same vessels,
      and, simultaneously, arterial distension was monitored using Optical coherence
      tomography (OCT). For each pulse train, the volume of fluid lost through
      filtration was measured (subtracting volume change due to residual distension)
      and compared with that predicted from steady pressure measurements. At 60- and 80
      mmHg baseline pressures, the experimental filtration volumes were significantly
      increased compared with those predicted for steady pressure (P < 0.05). OCT
      demonstrated that the excess fluid volume loss was significantly greater than the
      volume that would be lost through residual distension (P < 0.05). After 30 s, the
      magnitude of the excess of fluid loss was reduced. These results suggest that
      sudden onset of pulsatile pressure may cause changes in arterial interstitial
      hydration.

PMID- 14726306
TI  - Functional characterization and expression of PBR in rat gastric mucosa:
      stimulation of chloride secretion by PBR ligands.
AB  - Previous studies have demonstrated that gastric mucosa contained high levels of
      the polypeptide diazepam binding inhibitor, the endogenous ligand of the
      peripheral-type benzodiazepine receptor (PBR). However, the expression and
      function of this receptor protein in these tissues have not been investigated.
      Immunohistochemistry identified an intense PBR immunoreactivity in the mucous and
      parietal cells of rat gastric fundus and in the mucous cells of antrum.
      Immunoelectron microscopy revealed the mitochondrial localization of PBR in these
      cells. Binding of isoquinoline PK 11195 and benzodiazepine Ro5-4864 to gastric
      membranes showed that fundus had more PBR-binding sites than antrum, displaying
      higher affinity for PK 11195 than Ro5-4864. In a Ussing chamber, PK 11195 and Ro5
      4864 increased short-circuit current (I(sc)) in fundic and antral mucosa in a
      concentration-dependent manner in the presence of GABA(A) and central
      benzodiazepine receptor (CBR) blockers. This increase in I(sc) was abolished
      after external Cl(-) substitution and was sensitive to chloride channels or
      transporter inhibitors. PK 11195-induced chloride secretion was also 1) sensitive
      to verapamil and extracellular calcium depletion, 2) blocked by thapsigargin and
      intracellular calcium depletion, and 3) abolished by the mitochondrial pore
      transition complex inhibitor cyclosporine A. PK 11195 had no direct effect on
      H(+) secretion, indicating that it stimulates a component of Cl(-) secretion
      independent of acid secretion in fundic mucosa. These data demonstrate that
      mucous and parietal cells of the gastric mucosa express mitochondrial PBR
      functionally coupled to Ca(2+)-dependent Cl(-) secretion, possibly involved in
      the gastric mucosa protection.

PMID- 14726307
TI  - Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-kappa B
      signal transduction and IL-8 gene expression in colonic epithelial cells.
AB  - Several effects of bile acids (BAs) on colonic epithelial cells (CECs) have been
      described, including induction of proliferation and apoptosis. Some of these
      effects are mediated through activation of the NF-kappa B transcriptional system.
      In this study, we investigated the molecular mechanisms underlying the BA-induced
      gene expression in CECs. The human CEC line HT-29 and primary human CECs were
      treated with dilutions of salts of deoxycholic acid (DCA) and taurodeoxycholic
      acid (TDCA). NF-kappa B binding activity was analyzed with EMSA, RelA
      translocation with immunofluorescence, and I kappa B alpha- and RelA
      phosphorylation with Western blot analysis. IL-8 mRNA and protein expression were
      assessed by quantitative PCR and ELISA. Functional impact of NF-kappa B
      activation was determined by blocking the proteasome activity with MG132 or by
      preventing IKK activity with a dominant-negative IKK beta delivered by adenoviral
      dominant-negative (dn) IKK beta (Ad5dnIKK beta). DCA and TDCA induced IL-8
      expression in a dose- and time-dependent manner. It is interesting that DCA but
      not TDCA induced I kappa B alpha-phosphorylation, RelA translocation, and NF
      kappa B binding activity. Accordingly, the proteasome inhibitor MG132 blocked DCA
      but not TDCA-induced IL-8 gene expression. In contrast, TDCA-induced IL-8 gene
      expression correlated with enhanced RelA phosphorylation, which was blocked by
      Ad5dnIKK beta. Our data suggest that DCA-induced signal transduction mainly
      utilized the I kappa B degradation and RelA nuclear translocation pathway,
      whereas TDCA primarily induced IL-8 gene expression through RelA phosphorylation.
      These differences may have implications for the understanding of the
      pathophysiology of inflammation and carcinogenesis in the gut.

PMID- 14726308
TI  - Thermosensitive transient receptor potential channels in vagal afferent neurons
      of the mouse.
AB  - A number of transient receptor potential (TRP) channels has recently been shown
      to mediate cutaneous thermosensitivity. Sensitivity to warm and cool stimuli has
      been demonstrated in both human and animal gastrointestinal tract; however, the
      molecular mechanisms that underlie this have not been determined. Vagal afferent
      neurons with cell bodies in the nodose ganglion are known to mediate
      nonnociceptive sensation from the upper gut. In this study, isolated cultured
      nodose ganglion from the mouse neurons showed changes in cytoplasmic-free Ca(2+)
      concentrations over a range of temperatures, as well as to icilin (a TRPM8 and
      TRPN1 agonist) and capsaicin (a TRPV1 agonist). RT-PCR was used to show the
      presence of six temperature-sensitive TRP channel transcripts (TRPV1-4, TRPN1,
      and TRPM8) in whole nodose ganglia. In addition, RT-PCR of single nodose cell
      bodies, which had been retrogradely labeled from the upper gut, detected
      transcripts for TRPV1, TRPV2, TRPV4, TRPN1, and TRPM8 in a proportion of cells.
      Immunohistochemical labeling detected TRPV1 and TRPV2 proteins in nodose ganglia.
      The presence of TRP channel transcripts and proteins was also detected in cells
      within several regions of the gastrointestinal tract. Our results reveal that TRP
      channels are present in subsets of vagal afferent neurons that project to the
      stomach and may confer temperature sensitivity on these cells.

PMID- 14726309
TI  - Direct association and translocation of PKC-alpha with calponin.
AB  - Calponin has been implicated in the regulation of smooth muscle contraction
      through its interaction with F-actin and inhibition of the actin-activated
      MgATPase activity of phosphorylated myosin. Calponin has also been shown to
      interact with PKC. We have studied the interaction of calponin with PKC-alpha and
      with the low molecular weight heat-shock protein (HSP)27 in contraction of
      colonic smooth muscle cells. Particulate fractions from isolated smooth muscle
      cells were immunoprecipitated with antibodies to calponin and Western blot
      analyzed with antibodies to HSP27 and to PKC-alpha. Acetylcholine induced a
      sustained increase in the immunocomplexing of calponin with HSP27 and of calponin
      with PKC-alpha in the particulate fraction, indicating an association of the
      translocated proteins in the membrane. To examine whether the observed
      interaction in vivo is due to a direct interaction of calponin with PKC-alpha, a
      cDNA of 1.3 kb of human calponin gene was PCR amplified. PCR product encoding 622
      nt of calponin cDNA (nt 351-972 corresponding to amino acids 92-229) was
      expressed as fusion glutathione S-transferase (GST) protein in the vector pGEX
      KT. We have studied the direct association of GST-calponin fusion protein with
      recombinant PKC-alpha in vitro. Western blot analysis of the fractions collected
      after elution with reduced glutathione buffer (pH 8.0) show a coelution of GST
      calponin with PKC-alpha, indicating a direct association of GST-calponin with PKC
      alpha. These data suggest that there is a direct association of translocated
      calponin and PKC-alpha in the membrane and a role for the complex calponin-PKC
      alpha-HSP27, in contraction of colonic smooth muscle cells.

PMID- 14726310
TI  - Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant
      rats.
AB  - Using a gastrostomy-fed (GF) rat infant "pup-in-a-cup" model, the effects of
      protein deprivation and supplemental glutamine (Gln) and glutamate (Glu) were
      examined to test the hypothesis that Gln decreases the proinflammatory response
      induced by LPS in the developing infant rat small intestine. Four groups of 6- to
      7-day-old pups were fed a rat milk substitute (RMS), one providing 100% and three
      providing 25% of normal protein intake for another 6 days. Two of the 25% protein
      fed groups received supplemental Gln or Glu. GF and LPS treatment blunted body
      growth and intestinal villus height and increased intestinal cytokine-induced
      neutrophil chemoattractant (CINC) mRNA in the protein-deprived, non-Gln-treated
      group compared with mother-fed pups (P < 0.05). Gln blunted intestinal CINC mRNA
      (P < 0.05), but Glu did not. Intestinal CINC peptide in the LPS-treated pups
      provided 100 and 25% protein was elevated approximately 13-fold compared with the
      mother-reared pups (P < 0.001). Gln and Glu decreased intestinal CINC peptide by
      73 and 80%, respectively. GF, LPS-treated pups also had a higher level of plasma
      CINC peptide (P < 0.05). Gln but not Glu decreased plasma CINC peptide (P <
      0.05). An approximate sixfold elevation of intestinal MPO activity in the GF, LPS
      treated rats was decreased by Gln and Glu by 92% (P < 0.001) and 54% (P < 0.05),
      respectively. Intestinal and plasma TNF-alpha were increased in GF, LPS-treated
      pups (P < 0.01), and Gln and Glu both blunted this increase (P < 0.05) in the
      intestine but not in the plasma. The results indicate that Gln decreases the LPS
      induced inflammatory response in infant rat intestine under different conditions
      of protein intake.

PMID- 14726313
TI  - Health tsars.

PMID- 14726315
TI  - A revised classification of headache disorders.

PMID- 14726314
TI  - Recipients of blood or blood products "at vCJD risk".

PMID- 14726316
TI  - Long term cognitive dysfunction in older people after non-cardiac surgery.

PMID- 14726317
TI  - Ethics review roulette: what can we learn?

PMID- 14726318
TI  - WHO confirms avian flu outbreak in Hanoi.

PMID- 14726320
TI  - Risk of cancer from mobile phones is unclear.

PMID- 14726321
TI  - Inadequate regulations undermine India's health care.

PMID- 14726322
TI  - London hospital to face High Court for allegedly refusing to resuscitate disabled
      girl.

PMID- 14726333
TI  - WHO queries culling of civet cats.

PMID- 14726334
TI  - Report calls for universal health cover for all US citizens.

PMID- 14726335
TI  - WHO to revamp statistics to include sudden infant death syndrome.

PMID- 14726337
TI  - Zimbabwe s public sector doctors temporarily return to work.

PMID- 14726338
TI  - Arkansas plans to reward healthy employees.

PMID- 14726339
TI  - Urologists cleared of manslaughter now face GMC.

PMID- 14726340
TI  - University fee changes may deter poor students from studying medicine.

PMID- 14726341
TI  - Comparison of requirements of research ethics committees in 11 European countries
      for a non-invasive interventional study.

PMID- 14726342
TI  - Sex ratios in healthcare occupations: population based study.

PMID- 14726343
TI  - Gender gap in undergraduate experience and performance in obstetrics and
      gynaecology: analysis of clinical experience logs.

PMID- 14726344
TI  - Presentation on websites of possible benefits and harms from screening for breast
      cancer: cross sectional study.
AB  - OBJECTIVE: To investigate whether information on mammographic screening presented
      on websites by interest groups is balanced, is independent of source of funding,
      and reflects recent findings. DESIGN: Cross sectional study using a checklist
      with 17 information items. SETTING: 27 websites in Scandinavian and English
      speaking countries. RESULTS: The 13 sites from advocacy groups and the 11 from
      governmental institutions all recommended mammographic screening, whereas the
      three from consumer organisations questioned screening (P = 0.0007). All the
      advocacy groups accepted industry funding, apparently without restrictions. In
      contrast the three consumer organisations acknowledged the risk of bias related
      to industry funding, and two of them did not accept such funding at all. Advocacy
      groups and governmental organisations favoured information items that shed
      positive light on screening. The major harms of screening, overdiagnosis and
      overtreatment, were mentioned by only four of these groups, but by all three
      sites from consumer organisations (P = 0.02). In addition, the chosen information
      was often misleading or erroneous. The selection of information items for
      websites did not reflect recent findings, apart from the consumer sites, which
      were much more balanced and comprehensive than other sites (median of 9
      information items v 3 items, P = 0.03). CONCLUSIONS: The information material
      provided by professional advocacy groups and governmental organisations is
      information poor and severely biased in favour of screening. Few websites live up
      to accepted standards for informed consent such as those stated in the General
      Medical Council's guidelines.

PMID- 14726345
TI  - Surgical quality: review of Californian measures.

PMID- 14726346
TI  - Not everything that counts can be counted; not everything that can be counted
      counts.

PMID- 14726347
TI  - Severe life threatening malaria in endemic areas.

PMID- 14726348
TI  - Treating severe and complicated malaria.

PMID- 14726349
TI  - Glaucoma--2: treatment.

PMID- 14726350
TI  - Public involvement in health care.

PMID- 14726351
TI  - Using industrial processes to improve patient care.

PMID- 14726352
TI  - Death of the teaching autopsy: advances in technology have not reduced the value
      of the autopsy.

PMID- 14726353
TI  - Death of the teaching autopsy: autopsy findings are important to all clinicians,
      including general practitioners.

PMID- 14726354
TI  - Death of the teaching autopsy: hospital and coroners' postmortem examinations are
      different, not least in payment.

PMID- 14726355
TI  - Death of the teaching autopsy: autopsy is a success story in Cuba.

PMID- 14726356
TI  - Death of the teaching autopsy: histopathologists should not obtain consent for
      autopsy.

PMID- 14726357
TI  - Death of the teaching autopsy: in Hong Kong teaching autopsies have been
      championed in public mortuaries.

PMID- 14726359
TI  - Timing of simvastatin treatment: results are not strong enough to change
      practice.

PMID- 14726360
TI  - Timing of simvastatin treatment: trial is not reported according to CONSORT
      guidelines.

PMID- 14726361
TI  - Timing of simvastatin treatment: results are not what really matters.

PMID- 14726362
TI  - Timing of drug treatment is crucial.

PMID- 14726363
TI  - Timing of simvastatin treatment: no matter the time of day, does UK policy
      reflect the evidence?

PMID- 14726364
TI  - Resuscitation in pregnancy article omitted several points.

PMID- 14726365
TI  - Timing of simvastatin treatment: what about the shift workers?

PMID- 14726366
TI  - Parents key to reducing overweight in children: political pressure is needed.

PMID- 14726368
TI  - Parents key to reducing overweight in children: marketing targets children.

PMID- 14726369
TI  - Outbreak of severe acute respiratory syndrome in a tertiary hospital in
      Singapore, linked to an index patient with atypical presentation: epidemiological
      study.
AB  - OBJECTIVE: To describe an outbreak of severe acute respiratory syndrome (SARS) in
      a tertiary hospital in Singapore, linked to an index patient with atypical
      presentation, and the lessons learnt from it. DESIGN: Descriptive study. SETTING:
      A tertiary hospital in Singapore. PARTICIPANTS: Patients, healthcare workers, and
      visitors who contracted SARS in Singapore General Hospital. MAIN OUTCOME
      MEASURES: Probable SARS as defined by the World Health Organization. RESULTS: The
      index patient presented with gastrointestinal bleeding, initially without changes
      to his chest radiograph. Altogether 24 healthcare workers, 15 patients, and 12
      family members and visitors were infected. The incubation period ranged from
      three to eight days. Only 13 patients were isolated on their dates of onset.
      CONCLUSIONS: Atypical presentation of SARS infection must be taken into
      consideration when managing patients with a history of contact with SARS
      patients. The main gap in the containment strategy in this outbreak was the
      failure to identify the index patient as someone who had been discharged from a
      ward in another hospital that managed probable SARS cases. Strict infection
      control measures, a good surveillance system, early introduction of isolation
      procedures, and vigilant healthcare professionals are essential for controlling
      outbreaks.

PMID- 14726370
TI  - Randomised equivalence trial comparing three month and six month follow up of
      patients with hypertension by family practitioners.
AB  - OBJECTIVE: To compare blood pressure control, satisfaction, and adherence to drug
      treatment in patients with treated hypertension followed up by their family
      physicians either every three months or every six months for three years. DESIGN:
      Randomised equivalence clinical trial. Settings 50 family practices in south
      eastern Ontario, Canada. PARTICIPANTS: 609 patients aged 30-74 years with
      essential hypertension receiving drug treatment whose hypertension had been
      controlled for at least three months before entry into the study. RESULTS: 302
      patients were randomly assigned to follow up every three months and 307 to follow
      up every six months. Baseline variables in the two groups were similar. As
      expected, patients in the six month group had significantly fewer visits, but
      patients in both groups visited their doctor more frequently than their assigned
      interval. Mean blood pressure was similar in the groups, as was control of
      hypertension. Patient satisfaction and adherence to treatment were similar in the
      groups. About 20% of patients in each group had blood pressures that were out of
      control during the study. CONCLUSIONS: Follow up of patients with treated
      essential hypertension every six months is equivalent to follow up every three
      months. Patient satisfaction and adherence to treatment are the same for these
      follow up intervals. As about 20% of patients' hypertension was out of control at
      any time during the study in both groups, the frequency of follow up may not the
      most important factor in the control of patients' hypertension by family
      practitioners.

PMID- 14726371
TI  - Elevated telomerase activity and minimal telomere loss in cord blood long-term
      cultures with extensive stem cell replication.
AB  - Telomerase activity, telomere length, stem/progenitor cell production, and
      function of CD34+ cells from cord blood (CB), bone marrow, and mobilized
      peripheral blood were evaluated in long-term cultures. CB cells were cultured
      either on OP-9 stromal cells transduced with an adenovector expressing
      thrombopoietin (TPO) or stimulated by a cytokine cocktail in the absence of
      stroma, with, in one method, CD34+ cells reisolated at monthly intervals for
      passage. Continuous expansion of stem cells as measured by in vitro cobblestone
      area and secondary colony-forming assays was noted for 18 to 20 weeks and by
      severe combined immunodeficiency (SCID)-repopulating cells (SRCs), capable of
      repopulating and serially passage in nonobese diabetic/SCID mice, for 16 weeks.
      Despite this extensive proliferation, telomere length initially increased and
      only at late stages of culture was evidence of telomere shortening noted. This
      telomere stabilization correlated with maintenance of high levels of telomerase
      activity in the CD34+ cell population for prolonged periods of culture. Cytokine
      stimulated cultures of adult CD34+ cells showed CD34+ and SRC expansion (6-fold)
      for only 3 to 4 weeks with telomere shortening and low levels of telomerase.
      There is clearly a clinical value for a system that provides extensive stem cell
      expansion without concomitant telomere erosion.

PMID- 14726372
TI  - T-cell protein tyrosine phosphatase deletion results in progressive systemic
      inflammatory disease.
AB  - The deregulation of the immune response is a critical component in inflammatory
      disease. Recent in vitro data show that T-cell protein tyrosine phosphatase (TC
      PTP) is a negative regulator of cytokine signaling. Furthermore, tc-ptp(-/-) mice
      display immune defects and die within 5 weeks of birth. We report here that tc
      ptp(-/-) mice develop progressive systemic inflammatory disease as shown by
      chronic myocarditis, gastritis, nephritis, and sialadenitis as well as elevated
      serum interferon-gamma. The widespread mononuclear cellular infiltrates correlate
      with exaggerated interferon-gamma, tumor necrosis factor-alpha, interleukin-12,
      and nitric oxide production in vivo. Macrophages grown from tc-ptp(-/-) mice are
      inherently hypersensitive to lipopolysaccharide, which can also be detected in
      vivo as an increased susceptibility to endotoxic shock. These results identify T
      cell protein tyrosine phosphatase as a key modulator of inflammatory signals and
      macrophage function.

PMID- 14726373
TI  - Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for
      abnormal vascular function and thrombosis propensity.
AB  - Women with systemic lupus erythematosus (SLE) are at risk for premature
      atherothrombosis independent of Framingham risk factors. We investigated whether
      endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes
      to circulating tissue factor (TF) levels in this disease. Brachial artery flow
      mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in
      women with SLE, healthy control subjects, and subjects with coronary artery
      disease (CAD) (n = 43/group). Quantification of circulating apoptotic ECs was
      performed by flow cytometry (CD146(+) cells that stained for Annexin V
      [CD146(AnnV+)]) and immunofluorescent microscopy. Plasma TF was measured by
      enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD
      subjects, patients with SLE had higher numbers of circulating CD146(AnnV+) cells
      (10 +/- 3, 18 +/- 5, and 89 +/- 32 cells/mL, respectively, mean +/- SEM; P <.01).
      Increased CD146(AnnV+) cells correlated strongly with abnormal vascular function
      (P =.037). After adjusting for known predictors of endothelial function,
      CD146(AnnV+) was the only variable that predicted FMD (beta = -4.5, P <.001).
      Increased CD146(AnnV+) was strongly associated with elevated levels of
      circulating TF (r =.46, P =.002). Circulating apoptotic ECs are elevated in young
      women with SLE and strongly correlate with markedly abnormal vascular function
      and elevated TF levels. Heightened endothelial apoptosis may represent an
      important mechanism for development of atherothrombosis in SLE.

PMID- 14726374
TI  - SCL is required for normal function of short-term repopulating hematopoietic stem
      cells.
AB  - The stem cell leukemia (SCL) gene is essential for the development of
      hematopoietic stem cells in the embryo. Here, we used a conditional gene
      targeting approach to examine the function of SCL in adult hematopoietic stem
      cells (HSCs). Flow cytometry of bone marrow from SCL-deleted mice demonstrated a
      4-fold increase in number of Lin(neg) c-kit(+) Sca-1(+) cells. Despite this
      increase in the number of phenotypic HSCs, competitive repopulation assays
      demonstrated a severe multilineage defect in repopulation capacity by SCL-deleted
      bone marrow cells. SCL-heterozygous cells also showed a mild repopulation defect,
      thus suggesting haploinsufficiency of SCL. The transplantation defect of SCL
      deleted cells was observed within 4 weeks of transplantation, indicating a defect
      in a multipotent progenitor or short-term repopulating HSCs. Although the defect
      persisted in secondary transplants, it remained relatively stable, suggesting
      that SCL was not required for self-renewal of the HSCs. Generation of SCL-deleted
      cells within SCL-wild-type mice rescued the early repopulating defect. Together,
      our results suggest that SCL is required for the normal function of short-term
      repopulating HSCs.

PMID- 14726375
TI  - Granulocyte transmigration through the endothelium is regulated by the oxidase
      activity of vascular adhesion protein-1 (VAP-1).
AB  - Polymorphonuclear leukocytes (PMNs) migrate from the blood into areas of
      inflammation by binding to the endothelial cells of blood vessels via adhesion
      molecules. Vascular adhesion protein-1 (VAP-1) is one of the molecules mediating
      leukocyte-endothelial cell interactions. It is also an endothelial cell-surface
      enzyme (amine oxidase) that produces reactive oxygen species during the catalytic
      reaction. To study the role of the enzymatic activity of VAP-1 in PMN
      extravasation, we used an enzymatically inactive VAP-1 mutant, specific amine
      oxidase inhibitors (including a novel small molecule compound), and anti-VAP-1
      antibodies in several flow-dependent models. The enzyme inhibitors diminished PMN
      rolling on and transmigration through human endothelial cells under conditions of
      laminar shear stress in vitro. Notably, the enzyme inactivating point mutation
      abolished the capacity of VAP-1 to mediate transmigration. Moreover, the new VAP
      1 inhibitor effectively prevented the extravasation of PMNs in an animal model of
      inflammation. These data show that the oxidase activity of VAP-1 controls PMN
      exit from the blood during the relatively poorly understood transmigration step.

PMID- 14726376
TI  - Induction and maintenance therapy with intermittent interleukin-2 in HIV-1
      infection.
AB  - Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy
      can lead to substantial CD4 cell increases in many HIV-infected patients have
      generally been of limited duration. We studied 77 patients participating in
      active longitudinal studies of subcutaneous IL-2 therapy at our center in order
      to determine the long-term feasibility of this approach. Following initial
      induction, patients in each trial were eligible to receive intermittent 5-day
      cycles of subcutaneous IL-2 treatment at individualized doses and frequencies
      capable of maintaining CD4 counts at postinduction levels. The mean duration of
      study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline
      CD4 cell count and CD4 percent values of 0.521 x 10(9)/L (521 cells/microL) and
      27% have risen to 1.005 x 10(9)/L (1005 cells/microL) and 38%, respectively, at
      90 months. The mean number of subcutaneous IL-2 cycles required to achieve and
      maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean
      interval of cycling required to maintain these elevations is 39 months (median,
      35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is
      capable of maintaining CD4 cell increases for an extended period using a
      remarkably low frequency of intermittent cycling. These observations may
      contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term
      treatment strategy.

PMID- 14726377
TI  - Proteomics techniques and their application to hematology.
AB  - The recent sequencing of a number of genomes has raised the level of
      opportunities for studies on proteins. This area of research has been described
      with the all-embracing term, proteomics. In proteomics, the use of mass
      spectrometric techniques enables genomic databases to be used to establish the
      identity of proteins with relatively little data, compared to the era before
      genome sequencing. The use of related analytical techniques also offers the
      opportunity to gain information on regulation, via posttranslational
      modification, and potential new diagnostic and prognostic indicators. Relative
      quantification of proteins and peptides in cellular and extracellular material
      remains a challenge for proteomics and mass spectrometry. This review presents an
      analysis of the present and future impact of these proteomic technologies with
      emphasis on relative quantification for hematologic research giving an appraisal
      of their potential benefits.

PMID- 14726378
TI  - SAP mediates specific cytotoxic T-cell functions in X-linked lymphoproliferative
      disease.
AB  - Cytotoxic T cells (CTLs) and natural killer cells play a major role in the immune
      response to Epstein-Barr virus (EBV) infection. In X-linked lymphoproliferative
      (XLP) disease, a severe immunodeficiency, immunodysregulatory phenomena are
      observed following EBV infection, suggesting that defects exist in these effector
      populations. The gene defective in XLP is SAP (signaling lymphocytic activation
      molecule [SLAM]-associated protein), an adaptor protein that mediates signals
      through SLAM and other immunoglobulin superfamily receptors including 2B4. We
      generated EBV-specific T-cell lines from controls and XLP patients and examined
      CTL function in response to different stimuli. We show that XLP patients can
      generate EBV-T-cell lines that are phenotypically similar to those from controls.
      XLP patient EBV-T-cell lines showed a significant decrease in interferon-gamma
      (IFN-gamma) production in response to 2B4 and autologous EBV-transformed
      lymphoblastoid cell line (LCL) stimulation but not in response to SLAM.
      Furthermore, XLP EBV-T-cell lines demonstrated markedly decreased cytotoxic
      activity against autologous LCLs. By retroviral gene transfer of the SAP gene
      into XLP EBV-T-cell lines, we show reconstitution of IFN-gamma production and of
      cytotoxic activity confirming SAP-dependent defects. These studies demonstrate
      that in XLP the lack of SAP affects specific signaling pathways resulting in
      severe disruption of CTL function.

PMID- 14726379
TI  - Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of
      hematopoietic cell lines and primary megakaryocytic progenitors.
AB  - In this study we demonstrate that thrombopoietin (TPO)-stimulated Src family
      kinases (SFKs) inhibit cellular proliferation and megakaryocyte differentiation.
      Using the Src kinase inhibitors pyrolopyrimidine 1 and 2 (PP1, PP2), we show that
      TPO-dependent proliferation of BaF3/Mpl cells was enhanced at concentrations that
      are specific for SFKs. Similarly, proliferation is increased after introducing a
      dominant-negative form of Lyn into BaF3/Mpl cells. Murine marrow cells from Lyn
      deficient mice or wild-type mice cultured in the presence of the Src inhibitor,
      PP1, yielded a greater number of mature megakaryocytes and increased nuclear
      ploidy. Truncation and targeted mutation of the Mpl cytoplasmic domain indicate
      that Y112 is critical for Lyn activation. Examining the molecular mechanism for
      this antiproliferative effect, we determined that SFK inhibitors did not affect
      tyrosine phosphorylation of Janus kinase 2 (JAK2), Shc, signal transducer and
      activator of transcription (STAT)5, or STAT3. In contrast, pretreatment of cells
      with PP2 increased Erk1/2 (mitogen-activated protein kinase [MAPK])
      phosphorylation and in vitro kinase activity, particularly after prolonged TPO
      stimulation. Taken together, our results show that Mpl stimulation results in the
      activation of Lyn kinase, which appears to limit the proliferative response
      through a signaling cascade that regulates MAPK activity. These data suggest that
      SFKs modify the rate of TPO-induced proliferation and are likely to affect cell
      cycle regulation during megakaryocytopoiesis.

PMID- 14726380
TI  - Bioengineering of coagulation factor VIII for improved secretion.
AB  - Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood
      coagulation. Quantitative or qualitative deficiencies of FVIII result in the
      inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure
      A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude
      less efficient compared with other proteins of similar size compromising
      recombinant FVIII production and gene therapy strategies. FVIII expression is
      limited by unstable mRNA, interaction with endoplasmic reticulum (ER) chaperones,
      and a requirement for facilitated ER to Golgi transport through interaction with
      the mannose-binding lectin LMAN1. Bioengineering strategies can overcome each of
      these limitations. B-domain-deleted (BDD)-FVIII yields higher mRNA levels, and
      targeted point mutations within the A1 domain reduce interaction with the ER
      chaperone immunoglobulin-binding protein. In order to increase ER to Golgi
      transport we engineered several asparagine-linked oligosaccharides within a short
      B-domain spacer within BDD-FVIII. A bioengineered FVIII incorporating all of
      these elements was secreted 15- to 25-fold more efficiently than full-length
      FVIII both in vitro and in vivo. FVIII bioengineered for improved secretion will
      significantly increase potential for success in gene therapy strategies for
      hemophilia A as well as improve recombinant FVIII production in cell culture
      manufacturing or transgenic animals.

PMID- 14726382
TI  - X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism
      of NEMO reveals a critical role for NEMO in human T-cell development and/or
      survival.
AB  - X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID) is an X-linked
      recessive disease caused by a mutation in the nuclear factor-kappaB (NF-kappaB)
      essential modulator (NEMO). Here we report an XL-EDA-ID patient with atypical
      features of very few naive-phenotype T cells and defective mitogen-induced
      proliferation of peripheral blood mononuclear cells (PBMCs). The patient's NEMO
      defect was diagnosed by flow cytometric analysis of intracellular NEMO staining.
      Specific cell lineages (monocytes and neutrophils) expressed reduced levels of
      NEMO, but 2 populations of T, B, and NK cells were detected with normal and
      reduced expression of NEMO. Genomic analysis revealed that duplication of a 4.4
      kb sequence ranging from intron 3 to exon 6 caused the reduced expression of
      NEMO. Polymorphism analysis showed that the patient's B- and T-cell lines with
      reduced and normal expression of NEMO had the same X chromosome, indicating that
      the somatic mosaicism was not due to fetomaternal transfusion but was most likely
      due to postzygotic reversion. This XLEDA-ID case adds to our understanding of
      NEMO biology, indicating that NEMO is critical for T-cell development and/or
      survival in humans as well as in mice.

PMID- 14726383
TI  - Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other
      receptors.
AB  - Platelet adhesion to von Willebrand factor (VWF) activates alpha IIb beta 3, a
      prerequisite for thrombus formation. However, it is unclear whether the primary
      VWF receptor, glycoprotein (GP) Ib-IX-V, mediates alpha IIb beta 3 activation
      directly or through other signaling proteins physically associated with it (eg,
      FcR gamma-chain), possibly with the contribution of other agonist receptors and
      of VWF signaling through alpha IIb beta 3. To resolve this question, human and GP
      Ibalpha transgenic mouse platelets were plated on dimeric VWF A1 domain (dA1VWF),
      which engages only GP Ib-IX-V, in the presence of inhibitors of other agonist
      receptors. Platelet adhesion to dA1VWF induced Src kinase-dependent tyrosine
      phosphorylation of the FcR gamma-chain and the adapter molecule, ADAP, and
      triggered intracellular Ca(2+) oscillations and alpha IIb beta 3 activation.
      Inhibition of Ca(2+) oscillations with BAPTA-AM prevented alpha IIb beta 3
      activation but not tyrosine phosphorylation. Pharmacologic inhibition of protein
      kinase C (PKC) or phosphatidylinositol 3-kinase (PI 3-kinase) prevented alpha IIb
      beta 3 activation but not Ca(2+) oscillations. Inhibition of Src with 2 distinct
      compounds blocked all responses downstream of GP Ib-IX-V under static or flow
      conditions. However, dA1VWF-induced responses were reduced only slightly in GP
      Ibalpha transgenic platelets lacking FcR gamma-chain. These data establish that
      GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential
      actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC.

PMID- 14726384
TI  - TEL-AML1 promotes development of specific hematopoietic lineages consistent with
      preleukemic activity.
AB  - The t(12;21)(p13;q22) translocation is the most common chromosomal abnormality
      yet identified in any pediatric leukemia and gives rise to the TEL-AML1 fusion
      product. To investigate the effects of TEL-AML1 on hematopoiesis, fetal liver
      hematopoietic progenitor cells (HPCs) were transduced with retroviral vectors
      expressing this fusion protein. We show that TEL-AML1 dramatically alters
      differentiation of HPCs in vitro, preferentially promoting B-lymphocyte
      development, enhancing self-renewal of B-cell precursors, and leading to the
      establishment of long-term growth factor-dependent pre-B-cell lines. However, it
      had no effect on myeloid development in vitro. Further experiments were performed
      to determine whether TEL-AML1 also demonstrates lineage-specific activity in
      vivo. TEL-AML1-expressing HPCs displayed a competitive advantage in
      reconstituting both B-cell and myeloid lineages in vivo but had no effect on
      reconstitution of the T-cell lineage. Despite promoting these alterations in
      hematopoiesis, TEL-AML1 did not induce leukemia in transplanted mice. Our study
      provides a unique insight into the role of TEL-AML1 in leukemia predisposition
      and a potential model to study the mechanism of leukemogenesis associated with
      this fusion.

PMID- 14726385
TI  - Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53
      mutations and deletions.
AB  - The presence of p53 mutation or deletion predicts for poor response to
      conventional therapy in chronic lymphocytic leukemia (CLL). We sought to
      determine whether the humanized anti-CD52 antibody alemtuzumab was effective in
      this patient group. Thirty-six patients with fludarabine-refractory CLL were
      treated with alemtuzumab, 15 (42%) of whom had p53 mutations or deletions.
      Clinical responses in patients with p53 mutations, deletions, or both were noted
      in 6 (40%) of 15 versus 4 (19%) of 21 of patients without. The median response
      duration for this subset of patients was 8 months (range, 3-17 months). These
      data suggest that alemtuzumab may be an effective therapy for patients with CLL
      with p53 mutations or deletions.

PMID- 14726386
TI  - Transplantation tolerance induced by intranasal administration of HY peptides.
AB  - Induction of antigen-specific tolerance to transplantation antigens is desirable
      to control host-versus-graft and graft-versus-host reactions. Following molecular
      identification of a set of minor histocompatibility (H) antigens, we have used
      selected HY peptide epitopes for this purpose. Intranasal administration of
      individual major histocompatibility complex (MHC) class II-restricted HY peptides
      induces indefinite survival of syngeneic male skin grafts and allows engraftment
      of male bone marrow. Tolerance involves linked suppression to additional HY
      epitopes on test grafts. Long-term tolerance also requires suppression of
      emerging thymic emigrants. It does not involve deletion. HY peptide-specific
      CD4(+) and CD8(+) T cells expand on re-exposure to male antigen; these expansions
      are smaller in tolerant than control mice and fewer HY-specific cells from
      tolerant females secrete interferon gamma and interleukin 10 (IL-10).
      Significantly, CD4(+) cells from peptide-pretreated females fail to make IL-2
      responses to cognate peptide, limiting expansion of the HY-specific CD8(+)
      populations that can cause graft rejection. Consistent with this, tolerance
      induction by HY peptide is abrogated by coadministration of lipopolysaccharide.
      IL-10 does not appear to be critically involved because tolerance is inducible in
      IL-10-deficient mice. Adoptive transfer of tolerance into naive neonatal
      recipients by splenocytes from long-term tolerant donors provides evidence for
      involvement of regulatory cells.

PMID- 14726388
TI  - Hematopoiesis is severely altered in mice with an induced osteoblast deficiency.
AB  - We previously reported a transgenic mouse model expressing herpesvirus thymidine
      kinase (TK) gene under the control of a 2.3-kilobase fragment of the rat collagen
      alpha1 type I promoter (Col2.3 Delta TK). This construct confers lineage-specific
      expression in developing osteoblasts, allowing the conditional ablation of
      osteoblast lineage after treatment with ganciclovir (GCV). After GCV treatment
      these mice have profound alterations on bone formation leading to a progressive
      bone loss. In addition, treated animals also lose bone marrow cellularity. In
      this report we characterized hematopoietic parameters in GCV-treated Col2.3 Delta
      TK mice, and we show that after treatment transgenic animals lose lymphoid,
      erythroid, and myeloid progenitors in the bone marrow, followed by decreases in
      the number of hematopoietic stem cells (HSCs). Together with the decrease in bone
      marrow hematopoiesis, active extramedullary hematopoiesis was observed in the
      spleen and liver, as measured by an increase in peripheral HSCs and active
      primary in vitro hematopoiesis. After withdrawal of GCV, osteoblasts reappeared
      in the bone compartment together with a recovery of medullary and decrease in
      extramedullary hematopoiesis. These observations directly demonstrate the role of
      osteoblasts in hematopoiesis and provide a model to study the interactions
      between the mesenchymal and hematopoietic compartments in the marrow.

PMID- 14726387
TI  - Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical
      activity in patients with relapsed or refractory acute myeloid leukemia.
AB  - Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in
      approximately 30% of patients with de novo acute myeloid leukemia (AML) and are
      associated with lower cure rates from standard chemotherapy-based treatment.
      Targeting the mutation by inhibiting the tyrosine kinase activity of FLT3 is
      cytotoxic to cell lines and primary AML cells harboring FLT3 mutations.
      Successful FLT3 inhibition can also improve survival in mouse models of FLT3
      activated leukemia. CEP-701 is an orally available, novel, receptor tyrosine
      kinase inhibitor that selectively inhibits FLT3 autophosphorylation. We undertook
      a phase 1/2 trial to determine the in vivo hematologic effects of single-agent
      CEP-701 as salvage treatment for patients with refractory, relapsed, or poor-risk
      AML expressing FLT3-activating mutations. Fourteen heavily pretreated AML
      patients were treated with CEP-701 at an initial dose of 60 mg orally twice
      daily. CEP-701-related toxicities were minimal. Five patients had clinical
      evidence of biologic activity and measurable clinical response, including
      significant reductions in bone marrow and peripheral blood blasts. Laboratory
      data confirmed that clinical responses correlated with sustained FLT3 inhibition
      to CEP-701. Our results show that FLT3 inhibition is associated with clinical
      activity in AML patients harboring FLT3-activating mutations and indicate that
      CEP-701 holds promise as a novel, molecularly targeted therapy for this disease.

PMID- 14726389
TI  - Maturation of dendritic cells abrogates C1q production in vivo and in vitro.
AB  - Dendritic cells (DCs) and complement are essential components of the innate
      immune system. Immature DCs (immDCs) and mature DCs (mDCs) can migrate to
      lymphoid areas inducing, respectively, tolerance and immune responses. Primary
      deficiency of complement component C1q (C1q) leads to autoimmunity, suggesting a
      role in the maintenance of tolerance. In the present study, we investigated the
      production of C1q by immDCs, mDCs, and macrophages. We demonstrated that monocyte
      derived and CD34(+)-derived interstitial DCs are a rich source of C1q. C1q
      produced by immDCs is functionally active in complement activation and binding to
      apoptotic cells. The production of C1q is completely down-regulated upon DC
      maturation in vitro. Moreover, we found that DC differentiation in the presence
      of interferon-alpha (IFN-alpha) accelerated DC maturation and strongly impaired
      overall C1q production. Finally, we demonstrated the presence, in significant
      numbers, of DC-SIGN(+)/C1q(+) cells in T-cell areas of tonsils, next to DC
      LAMP(+) mDCs lacking C1q. We conclude from these results that immDC, a cell with
      tolerogenic properties, is a rich source of active C1q in vitro and in vivo,
      which is down-regulated on maturation. Therefore, immDCs may be considered an
      additional source of C1q in humans.

PMID- 14726390
TI  - Cytosolic phospholipase A2 type IVA is present in human red cells.
AB  - Phospholipase A(2) type IVA (IVAPLA(2)) is a cytosolic enzyme that on activation
      selectively releases arachidonic acid (AA) from cell membrane phospholipids. Both
      AA and lysophospholipid, products of the enzymic reaction, can function as signal
      transducers in cellular interactions. The enzyme is present in most cells,
      including polymorphs, eosinophils, and platelets. This study used affinity
      purification to extract IVAPLA(2) from red cell lysate prepared from leukocyte-
      and platelet-depleted human blood to overcome the masking effect of hemoglobin on
      Western blot detection. We show that IVAPLA(2) is present in red cells as a 90
      kDa protein.

PMID- 14726391
TI  - Dysregulated NK receptor expression in patients with lymphoproliferative disease
      of granular lymphocytes.
AB  - The natural killer (NK) type of lymphoproliferative disease of granular
      lymphocytes (LDGL) is associated with the expansion of CD3(-), CD16(+), and/or
      CD56(+) lymphocytes. We have examined the repertoire of NK receptors expressed on
      these cells and delineated the functional activity. We found skewed NK receptor
      expression on patient NK cells. Reactivity to a single anti-killer cell
      immunoglobulin-like receptor (anti-KIR) antibody was noted in 7 of 13 patients.
      LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA. In contrast, CD94
      and its inhibitory heterodimerization partner NKG2A were homogeneously expressed
      at high levels on these NK cells. Interestingly, these patients expressed a large
      number of activating KIR receptors by genotype analysis. Semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) demonstrated that lower than
      normal levels of RNA of the inhibitory KIR was present in some patients in
      contrast to normal NK cells. Consistent with a high level of activating
      receptors, we found the NK-LDGL cells have potent cytolytic function in both
      direct and redirected cytotoxicity assays. These results demonstrate that
      patients with NK-LDGL have an increased activating-to-inhibitory KIR ratio. This
      altered ratio might induce inappropriate lysis or cytokine production and impact
      the disease pathogenesis.

PMID- 14726392
TI  - WASp deficiency in mice results in failure to form osteoclast sealing zones and
      defects in bone resorption.
AB  - No defects related to deficiency of the Wiskott-Aldrich Syndrome protein (WASp)
      have been described in osteoclasts. Here we show that there are significant
      morphologic and functional abnormalities. WASp-null cells spread over a much
      larger surface area and are highly polykaryotic. In their migratory phase, normal
      cells assemble clusters of podosomes behind their leading edges, whereas during
      the bone resorptive phase multiple podosomes are densely aggregated in well
      defined actin rings forming the sealing zone. In comparison, WASp-null
      osteoclasts in either phase are markedly depleted of podosomes. On bone surfaces,
      this results in a failure to form actin rings at sealing zones. Complementation
      of WASp-null osteoclasts with an enhanced green fluorescent protein (eGFP)-WASp
      fusion protein restores normal cytoarchitecture. These structural disturbances
      translate into abnormal patterns of bone resorption both in vitro on bone slices
      and in vivo. Although physiologic steady-state levels of bone resorption are
      maintained, a major impairment is observed when WASp-null animals are exposed to
      a resorptive challenge. Our results provide clear evidence that WASp is a
      critical component of podosomes in osteoclasts and indicate a nonredundant role
      for WASp in the dynamic organization of these actin structures during bone
      resorption.

PMID- 14726393
TI  - Internal and external autocrine VEGF/KDR loops regulate survival of subsets of
      acute leukemia through distinct signaling pathways.
AB  - Besides being expressed on endothelial cells, vascular endothelial growth factor
      receptors (VEGFRs) are also functional on subsets of leukemias, resulting in
      autocrine loops that sustain leukemia migration and proliferation. While recent
      evidence suggests that VEGF supports hematopoietic stem cell survival via an
      internal loop, the molecular mechanisms whereby autocrine stimulation of VEGFR-2
      (KDR) promotes leukemia growth are not well understood. Here we show on acute
      myeloid primary leukemias and cell lines that VEGF/KDR autocrine loops operate
      both internally and externally. First, we demonstrate that KDR is constitutively
      phosphorylated and located at the nucleus of VEGF-producing leukemias. Treatment
      with anti-VEGF antibody, which acts externally, blocked KDR nuclear translocation
      and inhibited nuclear factor kappa B (NF-kappaB; p65 and c-rel) activation. In
      contrast, a KDR-specific intracellular inhibitor failed to block KDR nuclear
      translocation, but inhibited the constitutive activation of mitogen activated
      protein kinase (MAPK)/Erk and the phosphatidylinositol 3-kinase/AKT pathways.
      Notably, treatment with the anti-VEGF antibody alone had little effect on cell
      survival, while the internal inhibitor induced leukemia apoptosis, and the 2
      drugs produced synergistic effects, together and with chemotherapy, reducing cell
      survival to a larger extent than either agent alone. Our results demonstrate that
      internal and external VEGF/KDR autocrine loops regulate leukemia survival via
      different mechanisms, and suggest that blocking both may have therapeutic
      potential.

PMID- 14726394
TI  - Stem cell leukemia protein directs hematopoietic stem cell fate.
AB  - Stem cell leukemia (SCL) protein has been shown to be an essential transcription
      factor during hematopoietic development in the embryo. In adult hematopoiesis,
      however, the role for SCL has remained largely unknown, whereas it is expressed
      in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC
      transplantation and an in vitro HSC differentiation assay using retrovirally
      transduced HSCs with wild-type (WT) and dominant-negative (DN) SCL. The
      transplantation experiments showed that SCL does not affect the long-term
      repopulating capacity of HSCs but that WT SCL and DN SCL increase the short-term
      contribution of the transduced HSCs in myeloid and lymphoid lineages,
      respectively. An in vitro single-cell assay using a fetal thymus organ culture
      system further demonstrated that WT SCL facilitates HSCs to differentiate into
      the myeloid lineage but that DN SCL facilitates HSCs to differentiate into the
      lymphoid lineage. We conclude that the up-regulation or down-regulation of SCL
      directs HSCs toward myeloid or lymphoid lineage, respectively, although SCL does
      not affect their long-term repopulating capacity.

PMID- 14726395
TI  - Efficacy and safety of imatinib in adult patients with c-kit-positive acute
      myeloid leukemia.
AB  - This phase 2 pilot study was conducted to determine the efficacy and safety of
      imatinib mesylate in patients with c-kit-positive acute myeloid leukemia (AML)
      refractory to or not eligible for chemotherapy. Twenty-one patients were enrolled
      and received imatinib 600 mg orally once daily. Five responses were seen
      primarily in patients, starting with relatively low blast counts in bone marrow
      (BM) and peripheral blood (PB): 2 patients who were considered refractory on
      chemotherapy on the basis of persistence of blasts in PB and BM met the criteria
      for complete hematologic remission, 1 patient had no evidence of leukemia, and 2
      patients achieved a minor response. Treatment with imatinib demonstrated a good
      safety profile and was well tolerated. Western blot analysis and
      immunohistochemistry demonstrated c-Kit activation in primary AML cells. Further,
      imatinib treatment of primary AML cells inhibited c-Kit tyrosine-phosphorylation.
      Genomic DNA-sequencing of c-KIT showed no mutations in exons 2, 8, 10, 11, 12,
      and 17. Although some of the responses derived from relatively small reductions
      in leukemic blasts and may be attributable, in part, to prior chemotherapy, these
      cases suggest that imatinib has interesting clinical activity in a subset of
      patients with c-kit-positive AML. Further clinical trials are warranted to
      explore the clinical potential of imatinib in AML and to identify the underlying
      molecular mechanism.

PMID- 14726396
TI  - Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells.
AB  - Notch receptors expressed on hematopoietic stem cells interact with their ligands
      on bone marrow stromal cells and thereby control cell fate decisions and
      survival. We recently demonstrated that Notch signaling is involved in
      proliferation and survival of B cell-derived tumor cells of classic Hodgkin
      disease and described a novel mechanism for the oncogenic capacity of Notch. In
      this study we investigated whether Notch signaling is involved in the tight
      interactions between neoplastic plasma cells and their bone marrow
      microenvironment, which are essential for tumor cell growth in multiple myeloma
      (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are
      highly expressed in cultured and primary MM cells, whereas nonneoplastic
      counterparts show low to undetectable levels of Notch. Functional data indicate
      that ligand-induced Notch signaling is a growth factor for MM cells and suggest
      that these interactions contribute to myelomagenesis in vivo.

PMID- 14726397
TI  - Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+
      cells in poor mobilizers.
AB  - The activity of recombinant human growth hormone (rhGH) in enhancing CD34(+) cell
      mobilization elicited by chemotherapy plus recombinant human granulocyte colony
      stimulating factor (rhG-CSF) was evaluated in 16 hard-to-mobilize patients, that
      is, those achieving a peak of circulating CD34+ cells 10/microL or less, or a
      collection of CD34(+) cells equal to or less than 2 x 10(6)/kg. Patients who had
      failed a first mobilization attempt with chemotherapy plus rhG-CSF (5
      microg/kg/d) were remobilized with chemotherapy plus rhG-CSF and rhGH (100
      microg/kg/d). As compared with rhG-CSF, the combined rhGH/rhG-CSF treatment
      induced significantly higher (P < or =.05) median peak values for CD34(+)
      cells/microL (7 versus 29), colony-forming cells (CFCs)/mL (2154 versus 28,510),
      and long-term culture-initiating cells (LTC-ICs)/mL (25 versus 511). Following
      rhG-CSF and rhGH/rhG-CSF, the median yields of CD34(+) cells per leukapheresis
      were 1.1 x 10(6)/kg and 2.3 x 10(6)/kg (P < or =.008), respectively; the median
      total collections of CD34(+) cells were 1.1 x 10(6)/kg and 6 x 10(6)/kg (P < or
      =.008), respectively. No specific side effect could be ascribed to rhGH, except a
      transient hyperglycemia occurring in 2 patients. Reinfusion of rhGH/rhG-CSF
      mobilized cells following myeloablative therapy resulted in prompt hematopoietic
      recovery. In conclusion, our data demonstrate that in poor mobilizers addition of
      rhGH to rhG-CSF allows the patients to efficiently mobilize and collect CD34(+)
      cells with maintained functional properties.

PMID- 14726398
TI  - Congenital disorder of oxygen sensing: association of the homozygous Chuvash
      polycythemia VHL mutation with thrombosis and vascular abnormalities but not
      tumors.
AB  - Adaptation to hypoxia is critical for survival and regulates multiple processes,
      including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia
      sensing disorder characterized by homozygous mutation (598C>T) of von Hippel
      Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to
      the Chuvash population of Russia, this mutation occurs worldwide and originates
      from a single ancient event. That VHL 598C>T homozygosity causes elevated
      normoxic levels of the transcription factor hypoxia inducible factor-1alpha (HIF
      1alpha), serum erythropoietin and hemoglobin is known, but the disease phenotype
      has not been documented in a controlled manner. In this matched cohort study, VHL
      598C>T homozygosity was associated with vertebral hemangiomas, varicose veins,
      lower blood pressures, and elevated serum vascular endothelial growth factor
      (VEGF) concentrations (P <.0005), as well as premature mortality related to
      cerebral vascular events and peripheral thrombosis. Spinocerebellar
      hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical
      VHL syndrome were not found, suggesting that overexpression of HIF-1alpha and
      VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted serum
      erythropoietin concentrations were approximately 10-fold higher in VHL 598C>T
      homozygotes than in controls, erythropoietin response to hypoxia was identical.
      Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis,
      vascular abnormalities, and intact hypoxic regulation despite increased basal
      expression of hypoxia-regulated genes.

PMID- 14726399
TI  - Nicked beta2-glycoprotein I: a marker of cerebral infarct and a novel role in the
      negative feedback pathway of extrinsic fibrinolysis.
AB  - BEta(2)-glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in
      domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This
      cleavage may occur in vivo and elevated plasma levels of nicked beta(2)-GPI were
      detected in patients with massive plasmin generation and fibrinolysis turnover.
      In this study, we report higher prevalence of elevated ratio of nicked beta(2)
      GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy
      subjects with lacunar infarct (27%) when compared to healthy subjects with normal
      findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI
      might have a physiologic role beyond that of its parent molecule in patients with
      thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a
      negative feedback regulator has not been yet documented. We demonstrate that
      nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M,
      presumably mediated by the interaction between the fifth domain of nicked beta(2)
      GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2)-GPI also
      suppressed plasmin generation up to 70% in the presence of tissue plasminogen
      activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties.
      These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic
      fibrinolysis via a negative feedback pathway loop.

PMID- 14726400
TI  - Bcl-2 protein expression is the strongest independent prognostic factor of
      survival in primary cutaneous large B-cell lymphomas.
AB  - Bcl-2 protein expression has been associated with poor prognosis in patients with
      noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell
      lymphomas, the location on the leg, the round-cell morphology defined as the
      predominance of centroblasts and immunoblasts over large centrocytes, and
      multiple skin lesions were identified as adverse prognostic factors. The
      prognostic value of bcl-2 protein expression has not been studied in large series
      of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected
      by the French Study Group on Cutaneous Lymphomas. The prognostic value of age,
      sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase
      (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied.
      The overall 5-year specific survival rate was 65%. In univariate analysis,
      advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round
      cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly
      related to death from lymphoma. In multivariate analysis, bcl-2 expression (P
      =.0003), multiple skin lesions (P =.004), and age remained independent prognostic
      factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative
      patients were 41% and 89%, respectively (P <.0001). A new prognostic
      classification of primary cutaneous B-cell lymphoma should be based primarily on
      bcl-2 protein expression rather than the location of skin lesions.

PMID- 14726401
TI  - Reversal of bone marrow angiogenesis in chronic myeloid leukemia following
      imatinib mesylate (STI571) therapy.
AB  - The effect of imatinib mesylate (imatinib) therapy on angiogenesis and
      myelofibrosis was investigated and compared with interferon (IFN) and hydroxyurea
      (HU) in 98 patients with newly diagnosed Philadelphia chromosome-positive/BCR
      ABL(+) (Ph(+)/BCR-ABL(+)) chronic myeloid leukemia in first chronic phase and no
      other pretreatment. By means of immunostaining (CD34) and morphometry, a
      relationship between microvessel frequency and fiber density was detectable in
      initial bone marrow (BM) biopsies and sequential examinations after at least 8
      months of therapy. First-line monotherapy with imatinib induced a significant
      reduction (normalization in comparison with controls) of microvessels and
      reticulin fibers. In most patients, decrease in BM vascularity was associated
      with a complete cytogenetic response. A significant anti-angiogenic effect was
      also observed after HU treatment, contrasting with IFN administration or
      combination regimens (IFN plus HU). In conclusion, our data support the anti
      angiogenic capacity of imatinib by normalization of vascularity. In contrast,
      hematologic response following IFN treatment is independent from BM angiogenesis.

PMID- 14726403
TI  - Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression
      and activity in KSHV-infected endothelial cells.
AB  - Kaposi sarcoma (KS) is the most common AIDS-associated malignancy and is
      characterized by angiogenesis and the presence of spindle cells. Kaposi sarcoma
      associated herpesvirus (KSHV) is consistently associated with all clinical forms
      of KS, and in vitro infection of dermal microvascular endothelial cells (DMVECs)
      with KSHV recapitulates many of the features of KS, including transformation,
      spindle cell proliferation, and angiogenesis. To study the molecular mechanisms
      of KSHV pathogenesis, we compared the protein expression profiles of KSHV
      infected and uninfected DMVECs. This comparison revealed that heme oxygenase-1
      (HO-1), the inducible enzyme responsible for the rate-limiting step in heme
      catabolism, was up-regulated in infected endothelial cells. Recent evidence
      suggests that the products of heme catabolism have important roles in endothelial
      cell biology, including apoptosis and angiogenesis. Here we show that HO-1 mRNA
      and protein are up-regulated in KSHV-infected cultures. Comparison of oral and
      cutaneous AIDS-KS tissues with normal tissues revealed that HO-1 mRNA and protein
      were also up-regulated in vivo. Increased HO-1 enzymatic activity in vitro
      enhanced proliferation of KSHV-infected DMVECs in the presence of free heme.
      Treatment with the HO-1 inhibitor chromium mesoporphyrin IX abolished heme
      induced proliferation. These data suggest that HO-1 is a potential therapeutic
      target for KS that warrants further study.

PMID- 14726402
TI  - Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization
      of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in
      patients with advanced multiple myeloma.
AB  - Patients with multiple myeloma (MM) with mutated RAS are less likely to respond
      to chemotherapy and have a shortened survival. Therefore, targeting RAS
      farnesylation may be a novel approach to treatment of MM. We evaluated the
      activity and tolerability of the farnesyltransferase (FTase) inhibitor tipifarnib
      (Zarnestra) in a phase 2 trial as well as its ability to inhibit protein
      farnesylation and oncogenic pathways in patients with relapsed MM. Forty-three
      patients (median age, 62 years [range, 33-82 years]) with a median of 4 (range, 1
      6) chemotherapy regimens entered the study. Tipifarnib, 300 mg orally twice
      daily, was administered for 3 weeks every 4 weeks. The most common toxicity was
      fatigue occurring in 66% of patients. Other toxicities included diarrhea, nausea,
      neuropathy, anemia, and thrombocytopenia. Sixty-four percent of the patients had
      disease stabilization. Treatment with tipifarnib suppressed FTase (but not
      geranylgeranyltransferase I) in bone marrow and peripheral blood mononuclear
      cells and also inhibited the farnesylation of HDJ-2 in unfractionated mononuclear
      cells and purified myeloma cells. Inhibition of farnesylation did not correlate
      with disease stabilization. Finally, tipifarnib decreased the levels of
      phosphorylated Akt and STAT3 (signal transducer and activator of transcription 3)
      but not Erk1/2 (extracellular signal regulated kinase 1 and 2) in bone marrow
      cells. We conclude that tipifarnib is tolerable, can induce disease
      stabilization, and can inhibit farnesylation and oncogenic/tumor survival
      pathways.

PMID- 14726404
TI  - IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF
      related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic
      activity on leukemic cells.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF superfamily exerting cytotoxic activities toward tumor cells. Herein,
      we demonstrate that therapeutic concentrations of interferon alpha (IFNalpha)
      stimulate the expression of high levels of TRAIL mRNA and the release of elevated
      amounts of a soluble bioactive form of TRAIL (sTRAIL) in both human neutrophils
      and monocytes. Supernatants harvested from IFNalpha-treated neutrophils/monocytes
      elicited, on TRAIL-sensitive leukemic cell lines, proapoptotic activities that
      were significantly reduced by either a combination of TRAIL-R1/Fc and TRAIL-R2/Fc
      chimeras or neutralizing anti-TRAIL, anti-TRAIL-R1, and anti-TRAIL-R2 antibodies,
      suggesting that they were mediated by released sTRAIL acting on both TRAIL
      receptors. Since diseases such as chronic myeloid leukemia (CML) and melanoma are
      effectively treated with IFNalpha,we also demonstrate that CML neutrophils and
      peripheral blood mononuclear cells (PBMCs) cultured with IFNalpha at therapeutic
      concentrations retain the capacity of releasing sTRAIL, suggesting that CML
      leukocytes, in vivo, might represent an important source of sTRAIL. In this
      regard, we show that sTRAIL serum levels as well as leukocyte-associated TRAIL
      significantly increase in melanoma patients following IFNalpha administration.
      Collectively, these findings indicate that sTRAIL released by IFNalpha-activated
      neutrophils and monocytes contributes not only to the immunoregulatory actions
      but also to the therapeutic activities of IFNalpha.

PMID- 14726405
TI  - Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation:
      donor type matters.
AB  - Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and
      marrow transplantation. Previous analyses of risk factors for this complication
      were performed in heterogeneous populations, with dissimilar diagnosis and
      conditioning regimens. We postulated that HC is more prevalent in matched
      unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in
      matched related donor (MRD) transplantations. We performed a retrospective study
      on 105 acute lymphocytic leukemia patients treated with 12 Gy total body
      irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15;
      mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients
      receiving MRD transplants, 30% of recipients of mismatched related, and 40% of
      MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of
      MRD versus MUD). The excessive rate of HC among MUD and UCB patients became
      evident after the first 30 days after transplantation. Recipients younger than 26
      years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This
      donor type and age effect was independent of platelet engraftment, development of
      graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte
      globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell
      source. We concluded that HC is more prevalent in MUD and UCB transplantations.

PMID- 14726406
TI  - Donor treatment with pegylated G-CSF augments the generation of IL-10-producing
      regulatory T cells and promotes transplantation tolerance.
AB  - We investigated whether the protection from graft-versus-host disease (GVHD)
      afforded by donor treatment with granulocyte colony-stimulating factor (G-CSF)
      could be enhanced by dose escalation. Donor treatment with human G-CSF prevented
      GVHD in the B6 --> B6D2F1 murine model in a dose-dependent fashion, and murine G
      CSF provided equivalent protection from GVHD at 10-fold lower doses. Donor
      pretreatment with a single dose of pegylated G-CSF (peg-G-CSF) prevented GVHD to
      a significantly greater extent than standard G-CSF (survival, 75% versus 11%, P
      <.001). Donor T cells from peg-G-CSF-treated donors failed to proliferate to
      alloantigen and inhibited the responses of control T cells in an interleukin 10
      (IL-10)-dependent fashion in vitro. T cells from peg-G-CSF-treated IL-10(-/-)
      donors induced lethal GVHD; T cells from peg-G-CSF-treated wild-type (wt) donors
      promoted long-term survival. Whereas T cells from peg-G-CSF wt donors were able
      to regulate GVHD induced by T cells from control-treated donors, T cells from G
      CSF-treated wt donors and peg-G-CSF-treated IL-10(-/-) donors did not prevent
      mortality. Thus, peg-G-CSF is markedly superior to standard G-CSF for the
      prevention of GVHD following allogeneic stem cell transplantation (SCT), due to
      the generation of IL-10-producing regulatory T cells. These data support
      prospective clinical trials of peg-G-CSF-mobilized allogeneic blood SCT.

PMID- 14726407
TI  - Adult bone marrow-derived stem cells use R-cadherin to target sites of
      neovascularization in the developing retina.
AB  - Adult bone marrow contains a population of hematopoietic stem cells (HSCs) that
      can give rise to cells capable of targeting sites of neovascularization in the
      peripheral or retinal vasculature. However, relatively little is known about the
      mechanism of targeting of these cells to sites of neovascularization. We have
      analyzed subpopulations of HSCs for the expression of a variety of cell surface
      adhesion molecules and found that R-cadherin, a calcium-dependent cell-cell
      adhesion molecule important for normal retinal endothelial cell guidance, was
      preferentially expressed by functionally targeting HSCs. Preincubation of HSCs
      with function-blocking anti-R-cadherin antibodies or novel R-cadherin-specific
      peptide antagonists effectively prevented targeting of bone marrow-derived cells
      to the developing retinal vasculature in vivo. Whereas control-injected HSCs
      targeted to all 3 normal developing retinal vascular layers, blocking R-cadherin
      mediated adhesion resulted in mistargeting of the HSCs to the normally avascular
      outer retina. Our results suggest that vascular targeting of bone marrow-derived
      HSCs is dependent on mechanisms similar to those used by endogenous retinal
      vascular endothelial cells. Thus, R-cadherin antagonists may be useful in the
      treatment of neovascular diseases in which circulating HSCs contribute to
      abnormal angiogenesis.

PMID- 14726408
TI  - Risk of myocardial infarction and stroke in smokers is related to plasma levels
      of inflammation-sensitive proteins.
AB  - BACKGROUND: The extent to which differences in cardiovascular risk between
      smokers with similar daily tobacco consumption may be related to plasma levels of
      inflammation-sensitive proteins (ISP) and whether these proteins are associated
      with levels of carboxyhemoglobin (COHb%) have not been clarified. METHODS AND
      RESULTS: In a population-based cohort of 1489 never smokers, 1685 former smokers,
      and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid
      (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and
      ceruloplasmin were measured. COHb% levels were available for 2098 of them.
      Incidence of myocardial infarction, stroke, and death were monitored over 18.7+/
      4.7 years. The proportion with high ISP levels (ie, > or =2 ISP in the top
      quartile) increased progressively with daily tobacco consumption (P<0.01) and
      COHb% (P<0.01). In all smoking categories, the incidence of stroke, cardiac
      events, and death was related to ISP. In heavy smokers, high ISP levels were
      associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to
      2.03) for cardiac events and death, respectively. Corresponding figures for
      moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49),
      respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively.
      CONCLUSIONS: ISP levels are related to COHb% in smokers. High levels are
      associated with an increased cardiovascular risk.

PMID- 14726409
TI  - Angiopoietin 2 induces cell cycle arrest in endothelial cells: a possible
      mechanism involved in advanced plaque neovascularization.
AB  - OBJECTIVE: To characterize the molecules and the mechanisms regulating the
      neoangiogenetic process in advanced atherosclerotic plaques. METHODS AND RESULTS:
      Western blot and immunofluorescence analysis of atherosclerotic specimens
      demonstrated that unlike neovessels from early lesions that expressed vascular
      endothelial growth factor (VEGF) and angiopoietin1 (Angio1), vessels from
      advanced lesions expressed VEGF and angiopoietin 2 (Angio2). Moreover, only few
      neovessels from advanced lesions showed a positive immunostaining for
      proliferating cell nuclear antigen. Angio1-elicited and Angio2-elicited
      intracellular events in endothelial cells (EC) demonstrated that while Angio1
      triggered Erk1/Erk2 mitogen activated protein kinases (MAPK) and Akt activation,
      Angio2 (50 ng/mL) induced STAT5 activation and p21waf expression and increased
      the fraction of cells in G1. Both Angio2-mediated events were abrogated by
      expressing a dominant negative STAT5 construct (DeltaSTAT5). Consistent with the
      expression of Angio2 in neovessels of advanced lesions a transcriptionally active
      STAT5 was detected. Moreover, co-immunoprecipitation experiments revealed the
      presence of a STAT5/Tie2 molecular complex in neointima vessels from advanced,
      but not from early, lesions. CONCLUSIONS: In advanced lesions, the activation of
      the Tie2-mediated STAT5 signaling pathway may negatively regulate vessel growth.

PMID- 14726410
TI  - Graft-extrinsic cells predominate in vein graft arterialization.
AB  - OBJECTIVE: Vein graft disease involves neointimal smooth muscle cells, the
      origins of which are unclear. This study sought to characterize and quantitate
      vein graft infiltration by cells extrinsic to the graft in a mouse model of vein
      graft disease. METHODS AND RESULTS: Inferior vena cava-to-carotid artery
      interposition grafting between C57Bl/6 and congenic beta-galactosidase-expressing
      ROSA26 mice was performed. Vein grafts were harvested 6 weeks postoperatively and
      stained with X-gal. More than 60% of neointimal cells derived from the recipient,
      and 50% of these cells expressed smooth muscle alpha-actin. The distribution of
      donor and recipient-derived cells within this vein graft wall layer was
      distinctly focal, consistent with focal infiltration and expansion of progenitor
      cells. When bone marrow transplantation with congenic green fluorescent protein
      (GFP)-expressing cells was used in vein graft recipients 1 month before surgery,
      abundant GFP-expressing cells appeared in the media, but not the neointima, of
      mature grafts. Endothelial cells in mature grafts derived from graft-intrinsic
      and graft-extrinsic sources and were, in part, of bone marrow origin.
      CONCLUSIONS: Cells extrinsic to the graft, including bone marrow-derived cells,
      predominate during vein graft remodeling.

PMID- 14726411
TI  - Molecular mechanism for changes in proteoglycan binding on compositional changes
      of the core and the surface of low-density lipoprotein-containing human
      apolipoprotein B100.
AB  - OBJECTIVE: The aim of this study was to investigate the molecular mechanism for
      changes in proteoglycan binding and LDL receptor affinity on two compositional
      changes in LDL that have been associated with atherosclerosis: cholesterol
      enrichment of the core and modification by secretory group IIA phospholipase A2
      (sPLA2) of the surface. METHODS AND RESULTS: Transgenic mice expressing
      recombinant apolipoprotein (apo) B and sPLA2 were generated. Recombinant LDL were
      isolated and tested for their proteoglycan and LDL receptor-binding activity. The
      results show site A (residues 3148-3158) in apoB100 becomes functional in sPLA2
      modified LDL and that site A acts cooperatively with site B (residues 3359-3369),
      the primary proteoglycan-binding site in native LDL, in the binding of sPLA2
      modified LDL to proteoglycans. Our results also show that cholesterol enrichment
      of LDL is associated with increased affinity for proteoglycans and for the LDL
      receptor. This mechanism is likely mediated by a conformational change of site B
      and is independent of site A in apoB100. CONCLUSIONS: Site A in apoB100 becomes
      functional in sPLA2-modified LDL and acts cooperatively with site B resulting in
      increased proteoglycan-binding activity. The increased binding for proteoglycans
      of cholesterol-enriched LDL is solely dependent on site B.

PMID- 14726412
TI  - Regulation of endopeptidases EC3.4.24.15 and EC3.4.24.16 in vascular endothelial
      cells by cyclic strain: role of Gi protein signaling.
AB  - OBJECTIVE: Endopeptidase EC3.4.24.15 (EP24.15)- and EC3.4.24.16 (EP24.16)
      specific peptide hydrolysis plays an important role in endothelium-mediated
      vasoregulation. Given the significant influence of hemodynamic forces on vascular
      homeostasis and pathology, we postulated that these related peptidases may be
      mechanosensitive. The objective of this study, therefore, was to investigate the
      putative role of cyclic strain in regulating the expression and enzymatic
      activity of EP24.15 and EP24.16 in bovine aortic endothelial cells (BAECs).
      METHODS AND RESULTS: BAECs were cultured under conditions of defined cyclic
      strain (0% to 10% stretch, 60 cycles/min, 0 to 24 hours). Strain significantly
      increased EP24.15 and EP24.16 soluble activity in a force- and time-dependent
      manner, with elevations of 2.3+/-0.4- and 1.9+/-0.3-fold for EP24.15 and EP24.16,
      respectively, after 24 hours at 10% strain. Pharmacological agents and dominant
      negative G protein mutants used to selectively disrupt Gi(alpha)- and Gbetagamma
      mediated signaling pathways attenuated strain-dependent (24 hours, 5%) increases
      for both enzymes. Differences in the inhibitory profile for both enzymes were
      also noted, with EP24.15 displaying greater sensitivity to Gi(alpha2/3)
      inhibition and EP24.16 exhibiting greater sensitivity to Gi(alpha1/2) and
      Gbetagamma inhibition. Cyclic strain also increased levels of secreted EP24.15
      and EP24.16 activity by 2.6+/-0.02- and 3.6+/-0.2-fold, respectively, in addition
      to mRNA levels for both enzymes (EP24.15 +42%, EP24.16 +56%). CONCLUSIONS: Our
      findings suggest that cyclic strain putatively regulates both the mRNA expression
      and enzymatic function of EP24.15 and EP24.16 in BAECs via alternate Gi protein
      signaling pathways.

PMID- 14726414
TI  - Clinical significance of small dense low-density lipoprotein cholesterol levels
      determined by the simple precipitation method.
AB  - OBJECTIVE: Recently, we established a simple method for the quantification of
      small dense LDL cholesterol (C) using heparin-magnesium precipitation. The small
      dense LDL-C level was identical to cholesterol in the denser LDL fraction with a
      density of 1.044 to 1.063 g/mL. The aim of this study was to examine clinical
      significance of this precipitation method for small dense LDL-C. METHODS AND
      RESULTS: Small dense LDL-C was measured by a direct homogenous LDL-C assay in the
      supernatant that remained after heparin-magnesium precipitation with density
      <1.044 lipoproteins. In 313 normolipidemic subjects, the mean value of small
      dense LDL-C was 31+/-13 mg/dL. In 462 healthy subjects, small dense LDL-C levels
      were positively correlated with serum triglyceride and LDL-C and were inversely
      correlated with high-density lipoprotein cholesterol (HDL-C). Combined
      hyperlipidemia showed the highest small dense LDL-C level among the various types
      of hyperlipidemia. Patients with type 2 diabetes had an increased small dense LDL
      C level (55+/-17). Patients with coronary heart disease also had increased small
      dense LDL-C levels (53+/-30) irrespective of the presence of diabetes, whereas
      their LDL-C levels were comparable to those of normolipidemic controls (111+/-31
      versus 104+/-22). CONCLUSIONS: These results suggest that measurement of small
      dense LDL-C by the present precipitation method is useful to evaluate atherogenic
      risk and may be applicable to routine clinical examination.

PMID- 14726413
TI  - Verapamil increases the apolipoprotein-mediated release of cellular cholesterol
      by induction of ABCA1 expression via Liver X receptor-independent mechanism.
AB  - OBJECTIVE: Release of cellular cholesterol and phospholipid mediated by helical
      apolipoprotein and ATP-binding cassette transporter (ABC) A1 is a major source of
      plasma HDL. We investigated the effect of calcium channel blockers on this
      reaction. METHODS AND RESULTS: Expression of ABCA1, apoA-I-mediated cellular
      lipid release, and HDL production were enhanced in cAMP analogue-treated RAW264
      cells by verapamil, and similar effects were also observed with other calcium
      channel blockers. The verapamil treatment resulted in rapid increase in ABCA1
      protein and its mRNA, but not the ABCG1 mRNA, another target gene product of the
      nuclear receptor liver X receptor (LXR). By using the cells transfected with a
      mouse ABCA1 promoter-luciferase construct (-1238 to +57bp), verapamil was shown
      to enhance the transcriptional activity. However, it did not increase
      transcription of LXR response element-driven luciferase vector. CONCLUSIONS: The
      data demonstrated that verapamil increases ABCA1 expression through LXR
      independent mechanism and thereby increases apoA-I-mediated cellular lipid
      release and production of HDL.

PMID- 14726415
TI  - Human evidence that the cystatin C gene is implicated in focal progression of
      coronary artery disease.
AB  - OBJECTIVE: Overexpression of elastolytic cysteine and aspartic proteases, known
      as cathepsins, is implicated in atherogenesis. The potential significance of
      imbalance in expression between cathepsins and their inhibitor cystatin C in
      cardiovascular disease has been highlighted by the demonstration of cystatin C
      deficiency in human atherosclerosis and abdominal aortic aneurysms. METHODS AND
      RESULTS: We identified and characterized physiologically relevant polymorphisms
      in the promoter region of the cystatin C gene that influence cystatin C
      production and used these polymorphisms as a tool to examine the significance of
      cystatin C in coronary atherosclerosis in vivo in humans. Seven polymorphisms,
      all in strong-linkage disequilibrium, were identified in the cystatin C gene, of
      which 2 promoter polymorphisms (-82G/C and -78T/G) were functional in vitro in
      electromobility shift and transient transfection assays. Genotyping of 1105
      individuals (237 survivors of a first myocardial infarction before age 60 and 2
      independent groups comprising a total of 868 healthy individuals) revealed that
      the plasma cystatin C concentration was significantly lower in carriers of the
      mutant haplotype. Furthermore, the mutant haplotype was associated with a higher
      average number of stenoses per coronary artery segment in unselected
      postinfarction patients (N=237) undergoing routine coronary angiography.
      CONCLUSIONS: These results provide human evidence for an important role of
      cystatin C in coronary artery disease.

PMID- 14726417
TI  - Telomere shortening in human coronary artery diseases.
AB  - BACKGROUND: Increased cell turnover in response to injury is considered to be
      important in the development of atherosclerotic plaques. Telomere shortening has
      been shown to be associated with cell turnover. We assessed the telomere length
      of human coronary endothelial cells to clarify whether there is a relationship
      between telomere shortening and coronary artery disease (CAD). METHODS AND
      RESULTS: Coronary endothelial cells were obtained from 11 patients with CAD who
      underwent autopsy and 22 patients without CAD who underwent autopsy by scraping
      off the luminal surface of coronary arteries. DNA extracted from the endothelial
      cells were blotted and hybridized with telomere-specific oligonucleotide
      ([TTAGGG]4). The hybridization signal intensity, which represented telomeric DNA
      content, was standardized with centromeric DNA content (T/C ratio) to estimate
      telomere length. The T/C ratios were significantly smaller (P<0.0001) in CAD
      patients than in age-matched non-CAD patients (CAD patients, 0.462+/-0.135; non
      CAD patients, 1.002+/-0.212). In 6 individual CAD patients, the T/C ratio at the
      atherosclerotic lesion was significantly smaller (P<0.05) than that at the non
      atherosclerotic portion. CONCLUSIONS: These findings suggest that focal
      replicative senescence and telomere shortening of endothelial cells may play a
      critical role in coronary atherogenesis and CAD.

PMID- 14726416
TI  - Constitutive expression and involvement of cyclooxygenase-2 in human
      megakaryocytopoiesis.
AB  - OBJECTIVE: Cyclooxygenase-1 (COX-1), but not COX-2, is expressed in human
      platelets, and thromboxane A2 (TXA2) produced via COX-1 induces platelet
      aggregation. The objectives of this study were to investigate the expression of
      COX-1 and COX-2 during platelet differentiation and to determine whether these
      enzymes are involved in the differentiation. METHODS AND RESULTS: CD34+
      progenitor cells isolated from human cord blood were cultured with thrombopoietin
      and c-kit ligand. The cells differentiated into megakaryocytes (CD34-/CD41+)
      after 8 days of culture and into platelets (CD41+/prodium iodide-) after 14 days
      of culture. The CD34+cells expressed a trace of COX-1 gene and no COX-2 gene. On
      day 5, COX-2 gene expression was observed and continued throughout the remainder
      of the culture. COX-1 gene expression increased after 8 days of culture. The
      treatment of this liquid culture with indomethacin, a dual inhibitor of COX-1 and
      COX-2, and NS-398, a COX-2-specific inhibitor, suppressed megakaryocyte
      differentiation. In contrast, at a dose of 10(-7) M, mofezolac, which is a highly
      selective inhibitor of COX-1, did not affect differentiation. NS-398-induced
      suppression of megakaryocyte differentiation was partly abrogated by stable
      analogues of TXA2. CONCLUSIONS: We report here that COX-2 and COX-1 are
      constitutively expressed in megakaryocytes, and TXA2 produced by COX-2 plays an
      important role in megakaryocytopoiesis.

PMID- 14726418
TI  - Genetic relationships of Aglaonema species and cultivars inferred from AFLP
      markers.
AB  - BACKGROUND AND AIMS: Aglaonema is an important ornamental foliage plant genus,
      but genetic relationships among its species and cultivars have not been reported.
      This study analysed genetic relatedness of 54 cultivars derived from nine species
      using amplified fragment length polymorphism (AFLP) markers. METHODS: Initially,
      48 EcoRI + 2/MseI + 3 primer set combinations were screened, from which six
      primer sets that showed clear scoreable and highly polymorphic fragments were
      selected and used for AFLP reactions. AFLP fragments were scored and entered into
      a binary data matrix as discrete variables. Jaccard's coefficient of similarity
      was calculated for all pair-wise comparisons among the 54 cultivars, and a
      dendrogram was constructed by the unweighted pair-group method using the
      arithmetic average (UPGMA). KEY RESULTS: The number of AFLP fragments generated
      per primer set ranged from 59 to 112 with fragment sizes varying from 50 to 565
      bp. A total of 449 AFLP fragments was detected, of which 314 were polymorphic (70
      %). All cultivars were clearly differentiated by their AFLP fingerprints. The 54
      cultivars were divided into seven clusters; cultivars within each cluster
      generally share similar morphological characteristics. Cluster I contains 35
      cultivars, most of them are interspecific hybrids developed mainly from A.
      commutatum, A. crispum or A. nitidum. However, Jaccard's similarity coefficients
      among these hybrids are 0.84 or higher, suggesting that these popular hybrid
      cultivars are genetically much closer than previously thought. This genetic
      similarity may imply that A. nitidum and A. crispum are likely progenitors of A.
      commutatum. CONCLUSIONS: Results of this study demonstrate the efficiency and
      ease of using AFLP markers for investigating genetic relationships of ornamental
      foliage plants, a group usually propagated vegetatively. The AFLP markers
      developed will help future Aglaonema cultivar identification, germplasm
      conservation and new cultivar development.

PMID- 14726419
TI  - Root border cells take up and release glucose-C.
AB  - BACKGROUND AND AIMS: Border cells are released from the root tips of many plant
      species, and can remain viable in the rhizosphere for 1 week. Whether border
      cells are capable of controlled glucose exchange with their environment was
      investigated. METHODS: Border cells were removed from Zea mays L. root tips, and
      immersed in (14)C-labelled D-glucose. In one experiment, the hexose transport
      inhibitor, phlorizin, was used to investigate active glucose uptake from a range
      of glucose concentrations. In another experiment, glucose efflux from border
      cells was monitored over time. KEY RESULTS: Glucose uptake by the border cells
      increased with increasing glucose concentration from 0.2 to 20 mm. At 0.2 mm
      glucose, uptake was mainly active, as evidenced by the approx. 60 % inhibition
      with phlorizin. At 2 and 20 mm glucose, however, uptake was mainly via diffusion,
      as phlorizin inhibition was negligible. Glucose efflux increased with time for
      live border cells in both 2 and 20 mm glucose. There was no clear efflux/time
      pattern for heat-killed border cells. CONCLUSIONS: Border cells actively take up
      glucose, and also release it. Under our experimental conditions, glucose uptake
      and efflux were of similar order of magnitude. In the rhizosphere net glucose
      exchange will almost certainly depend on local soil conditions.

PMID- 14726420
TI  - Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment
      to the airway.
AB  - We reasoned that a prospective assessment of glucocorticoid withdrawal in
      subjects with asthma would provide insight into the basis for flares of the
      disease. We therefore enrolled 25 subjects with moderate persistent asthma and
      treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day)
      followed by a withdrawal period that lasted until peak expiratory airflow
      decreased by 25% and FEV(1) by 15% or 6 weeks elapsed. After glucocorticoid
      withdrawal, 13 of 25 subjects reached the target, whereas 12 subjects did not.
      The number of eosinophils in bronchial biopsies was increased by glucocorticoid
      withdrawal in both groups, but increases in airway T cells were found in only
      those with exacerbation. T-cell accumulation was a reflection of similar
      increases in both CD4(+) and CD8(+) T cells and was accompanied by increased
      expression of chemokine CCL5 (regulated upon activation, normal T cell expressed
      and secreted) in the airway epithelium without activation of the transcription
      factor nuclear factor-kappaB. The pattern of glucocorticoid-sensitive
      inflammation during an asthma exacerbation is more reminiscent of an antiviral
      response than an eosinophil-predominant response to allergen and implies an
      independent role for airway T cells in mediating asthma flares and in determining
      glucocorticoid efficacy in the treatment of this disease.

PMID- 14726421
TI  - A prospective, controlled trial of a protocol-based strategy to discontinue
      mechanical ventilation.
AB  - Weaning protocols can improve outcomes, but their efficacy may vary with patient
      and staff characteristics. In this prospective, controlled trial, we compared
      protocol-based weaning to usual, physician-directed weaning in a closed medical
      intensive care unit (ICU) with high physician staffing levels and structured,
      system-based rounds. Adult patients requiring mechanical ventilation for more
      than 24 hours were assigned to usual care (UC) or protocol weaning based on their
      hospital identification number. Patients assigned to UC (n=145) were managed at
      their physicians' discretion. Patients assigned to protocol (n=154) underwent
      daily screening and a spontaneous breathing trial by respiratory and nursing
      staff without physician intervention. There were no significant baseline
      differences in patient characteristics between groups. The proportion of patients
      (protocol vs. UC) who successfully discontinued mechanical ventilation (74.7% vs.
      75.2%, p=0.92), duration of mechanical ventilation (median [interquartile range]:
      60.4 hours [28.6-167.0 hours] vs. 68.0 hours [27.1-169.3 hours], p=0.61), ICU
      (25.3% vs. 28.3%) and hospital mortality (36.4% vs. 33.1%), ICU length of stay
      (115 vs. 146 hours), and rates of reinstituting mechanical ventilation (10.3% vs.
      9.0%) was similar. We conclude that protocol-directed weaning may be unnecessary
      in a closed ICU with generous physician staffing and structured rounds.

PMID- 14726422
TI  - Improvement of alveolar glutathione and lung function but not oxidative state in
      cystic fibrosis.
AB  - Chronic neutrophilic inflammation leads to oxidative damage, which may play an
      important role in the pathogenesis of cystic fibrosis lung disease.
      Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in
      patients with cystic fibrosis. Here we evaluated the effects of glutathione
      aerosol on lower airway glutathione levels, lung function, and oxidative status.
      Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari
      LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an
      AKITA inhalation device (Inamed, Gauting, Germany) was determined in six
      patients. In 17 additional patients bronchoalveolar lavage fluid was assessed
      before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg
      of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose.
      Glutathione concentration in lavage 1 hour postinhalation was increased three- to
      fourfold and was still almost doubled 12 hours postinhalation. FEV(1) transiently
      dropped after inhalation but increased compared with pretreatment values after 14
      days (p < 0.001). This improvement was not related to the lavage content of
      oxidized proteins and lipids, which did not change with treatment. These results
      show that, using a new inhalation device with high efficacy, glutathione
      treatment of the lower airways is feasible. Reversion of markers of oxidative
      injury may need longer treatment, higher doses, or different types of
      antioxidants.

PMID- 14726424
TI  - Relationship between renal sympathetic nerve activity and renal blood flow during
      natural behavior in rats.
AB  - The purpose of the present study was to determine the relationship between renal
      sympathetic nerve activity (RSNA) and renal blood flow (RBF) during normal daily
      activity in conscious, chronically instrumented Wistar rats (n = 8). The animal's
      behavior was classified as rapid eye movement (REM) sleep, non-REM (NREM) sleep,
      quiet awake, moving, and grooming states. On average RSNA was lowest during REM
      sleep, which was decreased by 39.0 +/- 3.2% (P < 0.05) relative to NREM sleep,
      and rose linearly with an increase in activity level in the order of quiet awake
      (by 10.9 +/- 1.8%, P < 0.05), moving (by 29.4 +/- 2.9%, P < 0.05), and grooming
      (by 65.3 +/- 3.9%, P < 0.05) relative to NREM sleep. By contrast, RBF was highest
      during REM sleep, which was increased by 4.8 +/- 0.7% (P < 0.05) relative to NREM
      sleep and decreased significantly (P < 0.05) by 5.5 +/- 0.6 and 6.6 +/- 0.5%
      during moving and grooming states, respectively, relative to NREM sleep. There
      was a significant (P < 0.05) inverse linear relationship between the percent
      changes in RSNA and RBF and between those in RSNA and renal vascular conductance.
      Furthermore, renal denervation (n = 8) abolished the changes in RBF induced by
      different natural behavioral activities. These results suggest that the changes
      in RSNA induced by natural behavioral activities had a significant influence on
      RBF.

PMID- 14726423
TI  - Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell
      size or gene expression.
AB  - Bronchial hyperresponsiveness in mild to moderate asthma may result from airway
      smooth muscle cell proliferation or acquisition of a hypercontractile phenotype.
      Because these cells have not been well characterized in mild to moderate asthma,
      we examined the morphometric and gene expression characteristics of smooth muscle
      cells in this subgroup of patients with asthma. Using bronchial biopsies from 14
      subjects with mild to moderate asthma and 15 control subjects, we quantified
      smooth muscle cell morphology by stereology and the expression of a panel of
      genes related to a hypercontractile phenotype of airway smooth muscle, using
      laser microdissection and two-step real-time polymerase chain reaction. We found
      that airway smooth muscle cell size was similar in both groups, but cell number
      was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of
      smooth muscle in the submucosa was increased 50-83% (p < 0.005). Gene expression
      profiling in smooth muscle cells showed no difference in the expression of genes
      encoding phenotypic markers in cells from healthy subjects and subjects with
      asthma (all p > 0.1). We conclude that airway smooth muscle proliferation is a
      pathologic characteristic of subjects with mild to moderate asthma. However,
      smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene
      expression changes of a hypercontractile phenotype observed in vitro.

PMID- 14726425
TI  - Dissociation of hypothalamic noradrenergic activity and sympathoadrenal responses
      to recurrent hypoglycemia.
AB  - This study evaluated whether attenuation of sympathoadrenal responses to
      recurrent hypoglycemia is mediated by diminished noradrenergic activity in the
      hypothalamus. Male Sprague-Dawley rats received either once daily insulin (1.0
      units/kg) injections or an equal administration of saline for 3 days. Both groups
      received an administration of insulin on the fourth day, during which blood
      glucose and plasma catecholamines were determined, and extracellular
      norepinephrine (NE) in the ventromedial hypothalamus (VMH) or paraventricular
      hypothalamic nucleus (PVN) was monitored with microdialysis. The peak response of
      plasma epinephrine to insulin-induced hypoglycemia (nadir approximately 3.2
      mmol/l) was significantly reduced during the fourth hypoglycemic episode (774 +/-
      134 pg/ml) compared with the first episode (2,561 +/- 410 pg/ml, P < 0.001).
      Baseline levels of extracellular NE were elevated approximately 25% (P = 0.07) in
      the VMH and approximately 46% (P = 0.03) in the PVN after multiple hypoglycemic
      episodes. There was no difference in noradrenergic activity during the first or
      fourth hypoglycemic episode in either brain area. The reduced sympathoadrenal
      output after recurrent hypoglycemia is likely postsynaptic from hypothalamic NE
      release or is mediated via a collateral pathway.

PMID- 14726426
TI  - Fatigue and recovery of dynamic and steady-state performance in frog skeletal
      muscle.
AB  - Muscle fatigue reflects alterations of both activation and cross-bridge function,
      which will have markedly different affects on steady-state vs. dynamic
      performance. Such differences offer insight into the specific origins of fatigue,
      its mechanical manifestation, and its consequences for animal movement. These
      were inferred using dynamic contractions (twitches and cyclic work as might occur
      during locomotion) and steady-state performance with maximal, sustained
      activation (tetani, stiffness, and isokinetic force) during fatigue and then
      recovery of frog (Rana pipiens) anterior tibialis muscle. Stiffness remained
      unaltered during early fatigue of force and then declined only 25% as force
      dropped 50%, suggesting a decline with fatigue in first the force-generating
      ability and then the number of cross bridges. The relationship between stiffness
      and force was different during fatigue and recovery; thus the number of cross
      bridges and force per cross bridge are not intimately linked. Twitch duration
      increased with fatigue and then recovered, with trajectories that were remarkably
      similar to and linear with changes in tetanic force, perhaps belying a common
      mechanism. Twitch force increased and then returned to resting levels during
      fatigue, reflecting a slowing of activation kinetics and a decline in cross
      bridge number and force. Net cyclic work fatigued to the degree of becoming
      negative when tetanic force had declined only 15%. Steady-state isokinetic force
      (i.e., shortening work) declined by 75%, while cyclic shortening work declined
      only 30%. Slowed activation kinetics were again responsible, augmenting cyclic
      shortening work but greatly augmenting lengthening work (reducing net work).
      Steady-state measures can thus seriously mislead regarding muscle performance in
      an animal during fatigue.

PMID- 14726427
TI  - Biotelemetry transmitter implantation in rodents: impact on growth and circadian
      rhythms.
AB  - The implantation of a biotelemetry transmitter for core body temperature (T(c))
      and motor activity (MA) measurements is hypothesized to have effects on growth
      and circadian rhythmicity depending on animal body-to-transmitter (B:T) size
      ratio. This study examined the impact of transmitter implantation (TM) on body
      weight, food intake (FI), water intake (WI), and circadian T(c) and MA rhythms in
      mice (23.8 +/- 0.04 g) and rats (311.5 +/- 5.1 g) receiving no treatment (NT),
      anesthesia, laparotomy (LAP), and TM. The B:T size ratio was 6:1 and 84:1 for
      mice and rats, respectively. In mice, body weight required 14 days to recover to
      presurgical levels and never attained the level of the other groups. FI recovered
      in 3 days, whereas WI never reached presurgical levels. Rat body weight did not
      decrease below presurgical levels. FI and WI recovered to presurgical levels in
      rats by day 2 postsurgery. Anesthesia decreased mouse body weight for 1 wk, but
      was without effect in rats. LAP significantly decreased body weight for 5 days in
      mice and 1 day in rats, showing a significant effect of the surgical procedure in
      the absence of TM in both species. Circadian T(c) and MA rhythms were evident
      within the first week in both species, indicating dissociation between circadian
      rhythmicity and recovery of growth variables. Cosinor analysis showed a TM effect
      on T(c) min, T(c) max, mesor, amplitude, and period of mice, whereas only the
      amplitude of the rhythm was affected in rats. These data indicate that a large
      B:T size ratio is associated with minimization of the adverse effects of surgical
      implantation. We recommend that B:T size ratio, recovery of presurgical body
      weight, and display of a robust circadian T(c) and MA rhythm be established
      before collection of biotelemetry data collection under an experimental paradigm.

PMID- 14726428
TI  - NMDA receptor blockade attenuates CCK-induced reduction of real feeding but not
      sham feeding.
AB  - Systemic injection of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate
      (NMDA) receptor ion channels, increases meal size and delays satiation. We
      examined whether MK-801 increases food intake by directly interfering with
      actions of cholecystokinin (CCK). Prior administration of MK-801 (100 microg/kg
      ip) reversed the inhibitory effects of CCK-8 (2 and 4 microg/kg ip) on real
      feeding of both liquid and solid foods. MK-801 alone did not alter 30-min sham
      intake of 15% sucrose compared with intake after saline. Furthermore, while CCK-8
      (2 or 4 microg/kg ip) reduced sham intake, this reduction was not attenuated by
      MK-801 pretreatment. To ascertain whether MK-801 attenuation of CCK-induced
      reduction of real feeding was associated with attenuated inhibition of gastric
      emptying, we tested the effect of MK-801 pretreatment on CCK-induced inhibition
      of gastric emptying of 5-ml saline loads. Ten-minute gastric emptying was
      accelerated after MK-801 (3.9 +/- 0.2 ml) compared with saline vehicle (2.72 +/-
      0.2 ml). CCK-8 (0.5 microg/kg ip) reduced 10-min emptying to 1.36 +/- 0.3 ml.
      Pretreatment with MK-801 did not significantly attenuate CCK-8-induced reduction
      of gastric emptying (0.9 +/- 0.4 ml). This series of experiments demonstrates
      that blockade of NMDA ion channels reverses inhibition of real feeding by CCK.
      However, neither inhibition of sham feeding nor inhibition of gastric emptying by
      CCK is attenuated by MK-801. Therefore, increased food intake after NMDA receptor
      blockade is not caused by a direct interference with CCK-induced satiation.
      Rather, increased real feeding, either in the presence or absence of CCK, depends
      on blockade of NMDA receptor participation in other post-oral feedback signals
      such as gastric sensation or gastric tone.

PMID- 14726429
TI  - ANG II-induced excitation of paraventricular nucleus magnocellular neurons: a
      role for glutamate interneurons.
AB  - The hypothalamic paraventricular nucleus (PVN) plays a critical role in
      cardiovascular and neuroendocrine regulation. ANG II (ANG) acts throughout the
      periphery in the maintenance of fluid-electrolyte homeostasis and has also been
      demonstrated to act as a neurotransmitter in PVN exerting considerable influence
      on neuronal excitability in this nucleus. The mechanisms underlying the ANG
      mediated excitation of PVN magnocellular neurons have yet to be determined. We
      have used whole cell patch-clamp techniques in hypothalamic slices to examine the
      effects of ANG on magnocellular neurons. Application of ANG resulted in a
      depolarization of magnocellular neurons, a response that was abolished in TTX,
      suggesting an indirect mechanism of action. Interestingly, ANG also increased the
      frequency of excitatory postsynaptic potentials/currents in magnocellular
      neurons, an effect that was abolished after application of the glutamate
      antagonist kynurenic acid. ANG was without effect on the amplitude of excitatory
      postsynaptic currents, suggesting a presynaptic action on an excitatory
      interneuron within PVN. The ANG-induced depolarization was shown to be sensitive
      to kynurenic acid, revealing the requisite role of glutamate in mediating the ANG
      induced excitation of magnocellular neurons. These observations indicate that the
      ANGergic excitation of magnocellular PVN neurons are dependent on an increase in
      glutamatergic input and thus highlight the importance of a glutamate interneuron
      in mediating the effects of this neurotransmitter.

PMID- 14726430
TI  - Phenotypical evidence for a gender difference in cardiac norepinephrine
      transporter function.
AB  - Norepinephrine transporter (NET) function has a central role in the regulation of
      synaptic norepinephrine concentrations. Clinical observations in orthostatic
      intolerance patients suggest a gender difference in NET function. We compared the
      cardiovascular response to selective NET inhibition with reboxetine between 12
      healthy men and 12 age-matched women. Finger blood pressure, brachial blood
      pressure, and heart rate were measured. The subjects underwent cardiovascular
      autonomic reflex testing and a graded head-up tilt test. In a separate study, we
      applied incremental concentrations of tyramine and isoproterenol through
      subcutaneous microdialysis catheters in eight men and in eight women. NET
      inhibition elicited a threefold greater increase in supine blood pressure in men
      than women (P < 0.05). The pressor response was driven by an increased cardiac
      output. The orthostatic heart rate increase during NET inhibition was greater in
      men than women (56 +/- 5 beats/min in men, 42 +/- 4 beats/min in women, P <
      0.001). In contrast, NET inhibition resulted in a similar suppression in the cold
      pressor and handgrip response, low-frequency blood pressure oscillations, and
      venous norepinephrine in the supine position. Men and women were similarly
      sensitive to the lipolytic effect of isoproterenol and tyramine. We conclude that
      NET inhibition results in more pronounced changes in cardiac regulation in men
      than women. Our observations suggest that the NET contribution to cardiac
      norepinephrine turnover may be decreased in women. The gender difference in NET
      function may not be expressed in tissues that are less NET dependent than the
      heart.

PMID- 14726431
TI  - Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired
      respiratory tract infection: a review of the continuing development of an
      innovative antimicrobial agent.
AB  - Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has
      been available for clinical use in a wide range of indications for over 20 years
      and is now used primarily in the treatment of community-acquired respiratory
      tract infections. Amoxicillin/clavulanate was developed to provide a potent broad
      spectrum of antibacterial activity, coverage of beta-lactamase-producing
      pathogens and a favourable pharmacokinetic/pharmacodynamic (PK/PD) profile. These
      factors have contributed to the high bacteriological and clinical efficacy of
      amoxicillin/clavulanate in respiratory tract infection over more than 20 years.
      This is against a background of increasing prevalence of antimicrobial
      resistance, notably the continued spread of beta-lactamase-mediated resistance in
      Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and
      quinolone resistance in Streptococcus pneumoniae. The low propensity of
      amoxicillin/clavulanate to select resistance mutations as well as a favourable
      PK/PD profile predictive of high bacteriological efficacy may account for the
      longevity of this combination in clinical use. However, in certain defined
      geographical areas, the emergence of S. pneumoniae strains with elevated
      penicillin MICs has been observed. In order to meet the need to treat drug
      resistant S. pneumoniae, two new high-dose amoxicillin/clavulanate formulations
      have been developed. A pharmacokinetically enhanced tablet dosage form of
      amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR in the
      USA), has been developed for use in adult respiratory tract infection due to drug
      resistant pathogens, such as S. pneumoniae with reduced susceptibility to
      penicillin, as well as beta-lactamase-producing H. influenzae and M. catarrhalis.
      Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600)
      is for paediatric use in persistent or recurrent acute otitis media where there
      are risk factors for the involvement of beta-lactamase-producing strains or S.
      pneumoniae with reduced penicillin susceptibility. In addition to high efficacy,
      amoxicillin/clavulanate has a well known safety and tolerance profile of the two
      new high-dose formulations are not significantly different from those of
      conventional formulations. Amoxicillin/clavulanate is included in guidelines and
      recommendations for the treatment of bacterial sinusitis, acute otitis media,
      community-acquired pneumonia and acute exacerbations of chronic bronchitis.
      Amoxicillin/clavulanate continues to be an important agent in the treatment of
      community-acquired respiratory tract infections, both now and in the future.

PMID- 14726434
TI  - Human chorionic gonadotropin-dependent regulation of 17beta-hydroxysteroid
      dehydrogenase type 4 in preovulatory follicles and its potential role in
      follicular luteinization.
AB  - 17Beta-hydroxysteroid dehydrogenase type 4 (17betaHSD4) has a unique multidomain
      structure, with one domain involved in 17beta-estradiol inactivation. The
      objective of the study was to investigate the regulation of 17betaHSD4 during
      human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine
      17betaHSD4 cDNA was cloned and was shown to encode a 735-amino acid protein that
      is highly conserved (81-87% identity) compared with other mammalian orthologs. RT
      PCR/Southern blot analyses were performed to study the regulation of 17betaHSD4
      transcripts in equine preovulatory follicles isolated between 0-39 h after hCG
      treatment. Results showed the presence of basal 17betaHSD4 mRNA expression before
      hCG treatment, but an increase was observed in follicles obtained 24 h after hCG
      (P < 0.05). Analyses of isolated preparations of granulosa and theca interna
      cells identified basal mRNA expression in both layers, but granulosa cells
      appeared as the predominant site of follicular 17betaHSD4 mRNA induction. A
      specific polyclonal antibody was raised against a fragment of the equine protein
      and used to study regulation of the 17betaHSD4 protein. Immunoblots showed an
      increase in full-length 17betaHSD4 protein in follicles 24 h after hCG (P <
      0.05), in keeping with mRNA results. Immunohistochemical data confirmed the
      induction of the enzyme in follicular cells after hCG treatment. Collectively,
      these results demonstrate that the gonadotropin-dependent induction of follicular
      luteinization is accompanied by an increase in 17betaHSD4 expression. Considering
      the estrogen-inactivating function of 17betaHSD4, its regulated expression in
      luteinizing preovulatory follicles appears as a potential complementary mechanism
      to reduce circulating levels of 17beta-estradiol after the LH surge.

PMID- 14726435
TI  - A novel immortalized human endometrial stromal cell line with normal
      progestational response.
AB  - Obtaining primary human endometrial stromal cells (HESCs) for in vitro studies is
      limited by the scarcity of adequate human material and the inability to passage
      these cells in culture for long periods. Immortalization of these cells would
      greatly facilitate studies; however, the process of immortalization often results
      in abnormal karyotypes and aberrant functional characteristics. To meet this
      need, we have introduced telomerase into cultured HESCs to prevent the normal
      shortening of telomeres observed in adult somatic cells during mitosis. We have
      now developed and analyzed a newly immortalized HESC line that contains no clonal
      chromosomal structural or numerical abnormalities. In addition, when compared
      with the primary unpassaged parent cells, the new cell line displayed similar
      biochemical endpoints after treatment with ovarian steroids. Classical
      decidualization response to estradiol plus medroxyprogesterone acetate were seen
      in both morphologically, and progestin was seen to induce or regulate the
      expression of IGF binding protein-1, fibronectin, prolactin, tissue factor,
      plasminogen activator inhibitor-1, and Fas/Fas ligand. In summary, an
      immortalized HESC line has been developed that is karyotypically,
      morphologically, and phenotypically similar to the primary parent cells, and it
      is a powerful and consistent resource for in vitro work.

PMID- 14726436
TI  - Photoperiodic regulation of type 2 deiodinase gene in Djungarian hamster:
      possible homologies between avian and mammalian photoperiodic regulation of
      reproduction.
AB  - The molecular mechanisms responsible for seasonal time measurement have yet to be
      fully described. Recently, we used differential analysis to identify that the
      type 2 iodothyronine deiodinase (Dio2) gene is responsible for the photoperiodic
      response of gonads in Japanese quail. It was found that expression of Dio2 in the
      mediobasal hypothalamus is induced by light and that T(3) content in the
      mediobasal hypothalamus increased under long day conditions. In addition, we
      showed that intracerebroventricular infusion of T(3) mimics photoperiodically
      induced testicular growth. Because it is well known that thyroid hormone is also
      essential for the maintenance of the seasonal reproductive changes in a number of
      mammals, we examined expression of Dio2 in Djungarian hamsters and found
      expression in the ependymal cell layer lining the infralateral walls of the third
      ventricle and the cell-clear zone overlying the tuberoinfundibular sulcus. Signal
      intensity was high under long days and weak under short days. Although light
      pulse did not affect Dio2 expression, melatonin injections decreased Dio2
      expression under long days. These results indicate that Dio2 may be involved in
      the regulation of seasonal reproduction in mammals in the same way as observed in
      birds.

PMID- 14726437
TI  - Estrogen deficiency accelerates murine autoimmune arthritis associated with
      receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenesis.
AB  - The aims of this study were to evaluate the in vivo effects of estrogen
      deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the
      possible relationship between immune dysregulation and receptor activator of
      nuclear factor-kappaB ligand (RANKL)-mediated osteoclastogenesis. Experimental
      studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated
      MRL/lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in
      younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely
      recovered by pharmacological levels of estrogen administration. A significant
      elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II
      collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent
      estrogen administration. A high proportion of CD4(+) T cells bearing RANKL was
      found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin
      mRNA was detected in the synovium. An increase in both osteoclast formation and
      bone resorption pits was found. These results indicate that estrogen deficiency
      may play a crucial role in acceleration of autoimmune arthritis associated with
      RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis.

PMID- 14726438
TI  - Tissue-specific regulation of growth hormone (GH) receptor and insulin-like
      growth factor-I gene expression in the pituitary and liver of GH-deficient
      (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH
      antagonist.
AB  - GH has diverse biological actions that are mediated by binding to a specific,
      high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific
      and a requirement for cellular responsiveness to GH. IGF-I is produced in
      multiple tissues and regulated in part by GH through GHR. In this study, we
      evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the
      levels with those derived from liver of bovine GH transgenic, GH antagonist
      transgenic, lit/lit mice, and their respective controls using real-time RT-PCR.
      In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH
      action in all three animal models, and there was a strong correlation between GHR
      and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA
      in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I
      expression in GH antagonist transgenic or lit/lit mice was similar to that
      observed in control animals. There were no differences of GHR mRNA levels in
      pituitary gland of any groups we examined. There was also no correlation between
      GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we
      found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each
      other in chronic GH excess or deficient state, and that regulation and
      correlation between local GHR and IGF-I mRNA levels induced by GH is different
      between liver and pituitary gland.

PMID- 14726439
TI  - Long-term treatment of lasofoxifene preserves bone mass and bone strength and
      does not adversely affect the uterus in ovariectomized rats.
AB  - The purpose of this study was to determine the long-term effects of lasofoxifene,
      a new selective estrogen receptor modulator, on bone mass, bone strength, and
      reproductive tissues in ovariectomized (OVX) rats. Sprague Dawley female rats at
      3.5 months of age were OVX and treated orally with lasofoxifene (60, 150, or 300
      microg/kg x d) for 52 wk. The urinary deoxypyridinoline/creatinine ratio was
      significantly lower in all lasofoxifene-treated OVX rats compared with OVX
      controls at wk 26. Peripheral quantitative computerized tomography analysis of
      proximal tibial metaphysis showed that the significant loss in trabecular content
      and density induced by OVX was significantly prevented by lasofoxifene treatment.
      Proximal tibial and lumber vertebral trabecular bone histomorphometric analysis
      showed that all doses of lasofoxifene significantly reduced OVX-induced bone loss
      by decreasing bone resorption and bone turnover. The ultimate strength, energy,
      and toughness of the fourth lumbar vertebral body in OVX rats treated with all
      doses of lasofoxifene were significantly higher compared with those in OVX
      controls, and did not differ significantly from those in sham controls. Uterine
      weight in OVX rats treated with lasofoxifene was slightly, but significantly,
      higher when compared with that in OVX controls, but was still much less than that
      in sham controls. No abnormal finding associated with lasofoxifene was observed
      with uterine histology examination. In summary, long-term treatment with
      lasofoxifene preserves bone mass and bone strength and does not adversely affect
      the uterus in OVX rats. These data suggest that lasofoxifene is an effective
      antiosteoporosis agent, and its efficacy and safety can be maintained over an
      extended period of time.

PMID- 14726440
TI  - Characterization of vasoconstrictor responses in small bovine adrenal cortical
      arteries in vitro.
AB  - The adrenal gland is highly vascularized with tightly regulated blood flow that
      is closely correlated with steroidogenesis. Mechanisms involved in the regulation
      of adrenal blood flow and vascular tone are largely unknown. The present study
      characterizes the contractile responses of isolated small cortical arteries from
      bovine adrenal glands. In endothelium-intact arteries, K(+), the thromboxane
      mimetic U46619, 5-hydroxytryptamine (5-HT), and endothelin-1 (ET-1) induced
      concentration-dependent contractions, whereas phenylephrine, norepinephrine, and
      ACTH were without effect. The EC(50)s for K(+), U46619, 5-HT, and ET-1 were 45 +/
      3 mm, 150 +/- 24 nm, 370 +/- 38 nm, and 2.8 +/- 0.8 nm, respectively.
      Contractions induced by U46619, 5-HT, and ET-1 were blocked by the thromboxane
      receptor antagonist SQ 29,548, the 5-HT(2A) receptor antagonist ketanserin, and
      the ET(A) receptor antagonist BQ 123, respectively. Removal of the endothelium
      caused a marked leftward shift of concentration responses to high K(+), U46619, 5
      HT, and ET-1, and revealed contractile responses to phenylephrine and
      norepinephrine. In U46619-preconstricted arteries, BQ 123 converted ET-1-induced
      contractions to relaxations (maximal relaxation of 57 +/- 8%), which were
      subsequently blocked by the ET(B) receptor antagonist BQ 788. The ET(B)-mediated
      relaxations were endothelium dependent and inhibited by the nitric oxide synthase
      inhibitor N-nitro-l-arginine, the cytochrome P450 inhibitor SKF 525A, and high
      extracellular K(+), but not by the cyclooxygenase inhibitor indomethacin. These
      results demonstrate that small adrenal cortical arteries are highly responsive to
      various vasoconstrictor agents. The forceful contractile responses of these
      arterioles are consistent with their potential role in the regulation of adrenal
      blood flow.

PMID- 14726441
TI  - An Intrinsic gamma-aminobutyric acid (GABA)ergic system in the adrenal cortex:
      findings from human and rat adrenal glands and the NCI-H295R cell line.
AB  - gamma-Aminobutyric acid (GABA), a major neurotransmitter in the central nervous
      system, also acts as a paracrine or autocrine signaling molecule in endocrine
      tissues such as the pancreatic islets, adenohypophysis, and testis. In the
      present study, we describe local GABA production and functional GABA(B) receptors
      in the adrenal cortex, possibly forming an auto- or paracrine GABAergic system.
      Using immunohistochemistry and RT-PCR, we localized the GABA-synthesizing enzyme
      glutamate decarboxylase 67 and the vesicular GABA transporter in steroid
      producing cells of the human and rat adrenal cortex. Immunocytochemistry, Western
      blots, and RT-PCR experiments demonstrated the presence of glutamate
      decarboxylase 67 in the human adrenocortical cell line NCI-H295R. Measurements of
      glutamate decarboxylase activity confirmed that, in these cells and in rat
      adrenals, glutamate is decarboxylated to form GABA. In addition, we found
      expression of the GABA(B(1a)), GABA(B(1e)), and GABA(B(2)) subunits of the
      heterodimeric GABA(B) receptor in NCI-H295R cells as shown by RT-PCR. GABA(B(1a))
      and its truncated splice variant GABA(B(1e)) were also found in human and rat
      adrenal glands. Immunostaining for the GABA(B(2)) subunit revealed its presence
      in the human and rat adrenal cortex and in NCI-H295R cells. The GABA(B) receptors
      we identified were functional because the GABA(B) agonist baclofen inhibited T
      type Ca(2+) currents in whole-cell patch clamp experiments on NCI-H295R cells.
      This effect was blocked by pertussis toxin. Furthermore, the alpha(2)-, alpha(3)
      , beta(2)-, beta(3)- gamma(2)-, and epsilon-subunits of the GABA(A) receptor were
      detected in this cell line by RT-PCR. Hence, we conclude that GABA is synthesized
      and stored by steroid-producing cells of the adrenal cortex and may influence
      these cells in a paracrine or autocrine manner.

PMID- 14726442
TI  - Gonadotropins enhance caspase-3 and -7 activity and apoptosis in the theca
      interstitial cells of rat preovulatory follicles in culture.
AB  - Apoptosis causes the elimination of ovarian germ cells and the atretic
      degeneration of ovarian follicles. Here we have used cultured rat preovulatory
      follicles to examine the regulation of effector caspase-3 and -7 in follicles
      undergoing apoptosis in the presence or absence of gonadotropins or IGF-I.
      Culturing follicles in the presence or absence of serum resulted in the induction
      of apoptosis of granulosa cells (GC), which was accompanied by effector caspase
      activation. Surprisingly, the addition of the survival factors LH or FSH, but not
      IGF-I, further increased caspase-3 and -7 activity. Immunohistochemistry studies
      of the LH- and FSH-treated follicles indicated that cleaved caspase-3 was
      predominantly localized to the peripheral theca-interstitial cells (TIC). Western
      blot analysis and caspase-3 and -7 activity assays of the separated follicular
      compartments confirmed that both LH and FSH treatments significantly enhance
      caspase-3 and -7 activity in TIC. The elevation in caspase-3 and -7 activity in
      TIC was accompanied by an increase in apoptosis. Interestingly, LH and FSH also
      induced an increase in caspase-3 and -7 activity in GC; however, this increase
      was accompanied by a decrease in apoptosis. Finally, we demonstrate that in
      freshly isolated preovulatory follicles and in antral follicles in intact
      ovaries, the expression level of procaspase-3 is significantly higher in TIC than
      in GC. Thus, LH and FSH have a dual effect on the cultured rat preovulatory
      follicle: an antiapoptotic effect on GC and a proapoptotic effect on TIC.

PMID- 14726443
TI  - Estrogen Induces Neuropeptide Y (NPY) Y1 receptor gene expression and
      responsiveness to NPY in gonadotrope-enriched pituitary cell cultures.
AB  - We showed previously that neuropeptide Y1 receptor (Y1R) expression is increased
      in the hypothalamus on proestrus afternoon and that this up-regulation of Y1R
      mRNA may permit neuropeptide Y (NPY) to facilitate release of the preovulatory
      GnRH surge. Because NPY also modulates LH release directly, we examined steroid
      regulation of Y1R expression in the female rat anterior pituitary. Treatment of
      female rats with estrogen in vivo decreased the levels of Y1R mRNA in the whole
      pituitary gland. In lactotrope/somatotrope-enriched pituitary cells separated by
      unit gravity sedimentation, 17beta-estradiol (E(2)) treatment likewise suppressed
      Y1R expression. In contrast, E(2) elevated Y1R mRNA in gonadotrope-enriched cell
      populations, indicating that estrogen regulates Y1R mRNA expression differently
      in gonadotropes vs. other pituitary cell types. After exposure to E(2), NPY
      augmented GnRH-induced LH release from gonadotrope-enriched cells in a manner
      requiring Y1R activation. Without steroid exposure, this augmentation
      disappeared, and with progesterone alone, NPY reduced GnRH-induced LH release. In
      addition, NPY inhibited prolactin secretion from primary pituitary cells in a
      steroid-free environment, but not in the presence of estrogen. These findings
      demonstrate that E(2) can directly up-regulate gonadotrope responsiveness to NPY
      and suggest that this action is mediated at least in part by E(2)'s ability to
      stimulate Y1R gene expression in gonadotropes. Our observations are consistent
      with the idea that this regulatory mechanism represents a component of E(2)'s
      positive feedback actions in pituitary gonadotropes. The biological importance of
      E(2)'s opposite effects on Y1R expression in other pituitary cell types remains
      to be determined.

PMID- 14726444
TI  - Comparison of the release of adipokines by adipose tissue, adipose tissue matrix,
      and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese
      humans.
AB  - The purpose of this study was to examine the source of adipokines released by the
      visceral and sc adipose tissues of obese humans. Human adipose tissue incubated
      in primary culture for 48 h released more prostaglandin E(2), IL-8, and IL-6 than
      adiponectin, whereas the release of plasminogen activator inhibitor 1 and
      hepatocyte growth factor was less than that of adiponectin but greater than that
      of leptin. IL-10 and TNFalpha were released in amounts less than those of leptin,
      whereas vascular endothelial growth factor and IL1-beta were released in much
      lower amounts. The accumulation of adipokines was also examined in the three
      fractions (adipose tissue matrix, isolated stromovascular cells, and adipocytes)
      obtained by collagenase digestion of adipose tissue. Over 90% of the adipokine
      release by adipose tissue, except for adiponectin and leptin, could be attributed
      to nonfat cells. Visceral adipose tissue released greater amounts of vascular
      endothelial growth factor, IL-6, and plasminogen activator inhibitor 1 compared
      with abdominal sc tissue. The greatly enhanced total release of TNFalpha, IL-8,
      and IL-10 by adipose tissue from individuals with a body mass index of 45
      compared with 32 was due to nonfat cells. Furthermore, most of the adipokine
      release by the nonfat cells of adipose tissue was due to cells retained in the
      tissue matrix after collagenase digestion.

PMID- 14726445
TI  - Constitutive expression of CYP1A1 in bovine cumulus oocyte-complexes in vitro:
      mechanisms and biological implications.
AB  - The arylhydrocarbon receptor (AhR) is known to mediate toxic responses to dioxin
      (2,3,7,8-tetrachlorodibenzo-p- dioxin) and related compounds and has been
      extensively characterized from a toxicological viewpoint. However, it has
      recently been reported that the AhR may have a central role in ovarian
      physiology. To investigate the role of AhR during oocyte maturation, we analyzed
      the expression of AhR, its nuclear partner AhR nuclear translocator, and the
      major target gene CYP1A1, in bovine cumulus-oocyte complexes (COCs) by
      semiquantitative RT-PCR and Western blot. Coexpression of AhR and AhR nuclear
      translocator was observed in both oocytes and surrounding cumulus cells before
      and after in vitro maturation (IVM). Furthermore, after IVM, both cell types
      showed a clear up-regulation of AhR mRNA compared with the expression at 0 h.
      Constitutive expression of CYP1A1 mRNA was observed in immature oocytes at the
      background level, whereas no expression was observed in the surrounding cumulus
      cells. Interestingly, a significant increase in CYP1A1 expression level was
      observed in both oocytes and cumulus cells after IVM. To further investigate the
      role of AhR in CYP1A1 up-regulation and oocyte maturation, COCs were treated
      throughout IVM with the AhR antagonists, alpha-naphthoflavone and resveratrol.
      Both antagonists decreased the level of CYP1A1 in COCs compared with controls.
      Furthermore, CYP1A1 down-regulation was accompanied by a reduced ability of
      oocytes to complete in vitro maturation until metaphase II stage. These results
      suggest that CYP1A1 induction in COCs is necessary for correct proceeding of in
      vitro oocyte maturation in bovine and suggest a physiological role of AhR during
      resumption of meiosis.

PMID- 14726446
TI  - Both thyroid hormone receptor (TR)beta 1 and TR beta 2 isoforms contribute to the
      regulation of hypothalamic thyrotropin-releasing hormone.
AB  - Thyroid hormones (TH) are essential regulators of vertebrate development and
      metabolism. Central mechanisms governing their production have evolved, with the
      beta-TH receptor (TRbeta) playing a key regulatory role in the negative feedback
      effects of circulating TH levels on production of hypothalamic TRH and
      hypophyseal TSH. Both TRbeta-isoforms (TRbeta1 and TRbeta2) are expressed in the
      hypothalamus and pituitary. However, their respective roles in TH-dependent
      transcriptional regulation of TRH are undefined. We confirmed the preferential
      role of TRbeta vs. TRalpha isoforms in TRH regulation in wild-type mice in vivo
      by using the TRbeta preferential agonist GC-1. We next determined the effects of
      tissue-specific rescue of TRbeta1 and TRbeta2 isoforms by somatic gene transfer
      in hypothalami of TRbeta null (TRbeta(-/-)) mice. TH-dependent TRH
      transcriptional repression was impaired in TRbeta(-/-) mice, but was restored by
      cotransfection of either TRbeta1 or TRbeta2 into the hypothalamus. TRbeta1, but
      not TRbeta2, displayed a role in ligand-independent activation. In situ
      hybridization was used to examine endogenous TRH expression in the
      paraventricular nucleus of the hypothalamus of TRbeta(-/-) or TRalpha null
      (TRalpha(o/o)) mice under different thyroid states. In contrast to published data
      on TRbeta2(-/-) mice, we found that both ligand-independent TRH activation and
      ligand-dependent TRH repression were severely impaired in TRbeta(-/-) mice. This
      study thus provides functional in vivo data showing that both TRbeta1 and TRbeta2
      isoforms have specific roles in regulating TRH transcription.

PMID- 14726447
TI  - Annexin II is a thiazolidinedione-responsive gene involved in insulin-induced
      glucose transporter isoform 4 translocation in 3T3-L1 adipocytes.
AB  - The target genes of peroxisomal proliferator-activated receptor-gamma ligands
      that lead to insulin sensitization are not fully understood. In this study, we
      have found that the thiazolidinedione, troglitazone, increases expression of
      annexin II at both the mRNA and protein levels, raising the possibility that
      annexin II plays a role in insulin-stimulated glucose transporter isoform 4
      (GLUT4) translocation and glucose transport. To assess this, we microinjected
      annexin II antibody or annexin II small interfering RNA into 3T3-L1 adipocytes
      and found that insulin-stimulated GLUT4 translocation was inhibited by 54 and
      60%, respectively. Furthermore, microinjection of annexin II antibody inhibited
      constitutively active Galphaq (Q209L-Galphaq)-induced but not osmotic shock
      induced GLUT4 translocation. When cells were cotransfected with wild-type annexin
      II, along with an enhanced green fluorescent protein-cmyc-GLUT4 construct, and
      the percentage of cells expressing cmyc-GLUT4 at the cell surface was measured by
      immunofluorescence microscopy, there was a marked increase in the ability of
      insulin to stimulate recruitment of cmyc-GLUT4 protein to the cell surface. In
      summary, our results show that annexin II is a newly described thiazolidinedione
      response gene involved in insulin-induced GLUT4 translocation in 3T3-L1
      adipocytes.

PMID- 14726448
TI  - Identification of a functional peroxisome proliferator-activated receptor
      responsive element within the murine perilipin gene.
AB  - Perilipin, a family of phosphoproteins located around lipid droplets in
      adipocytes, is essential for enlargement of lipid droplets and lipolytic reaction
      by hormone-sensitive lipase. Thiazolidinediones, peroxisome proliferator
      activated receptor (PPAR) gamma agonists, have been shown to increase perilipin
      expression in fully differentiated adipocytes. However, the precise mechanism of
      transcriptional regulation of murine perilipin gene heretofore remains unclear.
      We determined the transcription start site of murine perilipin gene by RNA ligase
      mediated rapid amplification of the cDNA ends method. We generated luciferase
      reporter gene constructs containing various lengths of the 5'-flanking region of
      the murine perilipin gene and assayed promoter/enhancer activities using
      differentiated 3T3-L1 adipocytes. We identified a functional PPAR-responsive
      element (PPRE) in the murine perilipin promoter, and this was confirmed by gel
      EMSAs using nuclear extracts from differentiated 3T3-L1 adipocytes. Furthermore,
      point mutations of the identified functional PPRE markedly reduced both the
      reporter gene activity in differentiated 3T3-L1 adipocytes and
      PPARgamma/thiazolidinedione-induced transactivation in NIH-3T3 fibroblasts. Real
      time RT-PCR revealed that thiazolidinedione up-regulates endogenous perilipin
      mRNA levels. We propose that PPARgamma plays a significant role in the
      transcriptional regulation of murine perilipin gene via the PPRE in its promoter.

PMID- 14726449
TI  - Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH)
      independently of luteinizing hormone activity: evidence from genetic models of
      isolated FSH action.
AB  - Defining the gonadal effects of FSH distinct from those of LH remains difficult.
      We have characterized and compared the level of Sertoli and germ cell development
      in three mouse models recently created to isolate FSH activity from LH effects.
      Two models used LH-deficient hypogonadal (hpg) mice to selectively study either
      pituitary-independent transgenic (tg) FSH or ligand-independent activated tg FSH
      receptor (FSHR(+)) expression, and the third model used LH receptor (LHR)
      deficient mice to isolate and examine endogenous mouse FSH effects. Stereological
      evaluation revealed tg-FSH or tg-FSHR(+) activity significantly increased total
      Sertoli cell numbers per testis in both hpg models relative to control hpg
      testes. Furthermore, tg-FSH dose-dependently restored hpg Sertoli cells to wild
      type (wt) (non-hpg) levels, and LHR-/- testes also exhibited wt Sertoli numbers.
      Spermatogonial proliferation and meiotic development were enhanced by tg-FSHR(+)
      or tg-FSH. Despite producing normal Sertoli numbers, isolated tg-FSH activity
      only increased total spermatogonia and spermatocyte populations to 57 and 44% of
      wt, which was comparable to spermatogonia and spermatocyte numbers observed in
      LHR-null testes (45 and 34% of wt). Selective FSH activity initiated round
      spermatid formation in all three models. However, elongated spermatid formation
      was detected in tg-FSH and tg-FSHR(+) hpg testes but not in LHR-/- testes, which
      may reflect even lower intratesticular testosterone levels in LHR-null compared
      with hpg testes. FSH increased round and elongated spermatid numbers in hpg
      testes to 16 and 6% of wt without altering intratesticular testosterone levels,
      but failed to produce spermatozoa demonstrating the inability of FSH to complete
      spermatogenesis. These findings revealed that full Sertoli cell proliferation can
      be accomplished by FSH activity without LH requirement, and although postnatal
      mitotic and meiotic germ cell development can be promoted by FSH alone, LH
      mediated effects remain a critical determinant for initiating the full complement
      of germ cells and final stages of postmeiotic development.

PMID- 14726450
TI  - A novel missense mutation in the mouse growth hormone gene causes semidominant
      dwarfism, hyperghrelinemia, and obesity.
AB  - The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that
      carries an a-->g missense mutation in exon 5 of the GH gene, which translates to
      a D167G amino acid exchange in the mature protein. Mice carrying the mutation are
      characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence
      (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice
      displaying a less pronounced phenotype. All genotypes are viable and fertile, and
      the mode of inheritance is in accordance with a semidominant Mendelian trait.
      Adult SMA1 mice accumulate excessive amounts of sc and visceral fat in the
      presence of elevated plasma ghrelin levels, possibly reflecting altered energy
      partitioning. Our results suggest impaired storage and/or secretion of pituitary
      GH in mutants, resulting in reduced pituitary GH and reduced GH-stimulated IGF-1
      expression. Generation and identification of the SMA1 mouse exemplifies the power
      of the combination of random mouse mutagenesis with a highly detailed phenotype
      analysis as a successful strategy for the detection and analysis of novel gene
      function relationships.

PMID- 14726451
TI  - Reproductive abnormalities in human insulin-like growth factor-binding protein-1
      transgenic male mice.
AB  - Adult transgenic mice overexpressing human insulin-like growth factor-binding
      protein-1 in the liver present reproductive abnormalities in both sexes. In the
      present work, we have investigated the mechanisms responsible for limiting
      breeding capacity in these transgenic male mice. Homozygous adult transgenic male
      mice (3-6 months old) exhibited irregular copulatory behavior and a reduction of
      the number of pregnancies per female as well as of litter size per pregnancy.
      Genital tract weight, more specifically epididymal and seminal vesicle weights,
      were reduced by 45% in homozygous transgenic vs. nontransgenic mice. Homozygous
      transgenic mice exhibited a 30% reduction of the length of seminiferous tubules
      (P = 0.007), a 30% decrease in daily sperm production per testis (P = 0.019), and
      a 50% decrease in the number of spermatozoa in testis (P = 0.037), associated
      with morphological abnormalities of the sperm heads leading to an approximately
      50% reduction of fertilized two-cell eggs (P = 0.002) and of implanted embryos on
      d 5.5 after mating (P = 0.004). The round spermatids also appeared altered in
      their morphology. In addition, Leydig cells in homozygous transgenic mice
      exhibited an altered appearance, with a 1.8-fold increase in lipid droplets in
      their cytoplasm (P < 0.001). Moreover, the concentration of 3beta-hydroxysteroid
      dehydrogenase was 66% lower in testis from transgenics compared with those from
      normal mice (P = 0.01), leading to a tendency toward lower plasma testosterone
      levels (P = 0.1). Interestingly, LH concentrations were increased by 40% in
      transgenic pituitary extracts (P = 0.02), and basal LH secretion by pituitary
      explants in vitro was increased by 60% in homozygous transgenic vs. normal mice
      (P = 0.04), suggesting an alteration of LH pulsatile secretion in vivo. In
      conclusion, these data suggest that the breeding impairment of human insulin-like
      growth factor-binding protein-1 transgenic males is due at least in part to an
      alteration of the process of spermatogenesis, leading to a diminution of sperm
      production and of its quality. Minor impairment of steroidogenesis may also
      contribute to the reduced reproductive capacity of these animals. Our
      observations are consistent with the idea that normal spermatogenesis and perhaps
      also steroidogenesis are dependent on the actions of sufficient concentrations of
      unbound IGF-I.

PMID- 14726452
TI  - Regulation of Fgf10 gene expression in the prostate: identification of
      transforming growth factor-beta1 and promoter elements.
AB  - Fibroblast growth factor 10 (FGF10) is a mesenchymal paracrine-acting factor that
      plays a key role in the organogenesis of the prostate, and Fgf10 transcripts
      exhibit a highly restricted expression pattern within prostatic mesenchyme. To
      study the regulation of Fgf10 we have used organ rudiments grown in vitro as well
      as a primary stromal cell system derived from the ventral mesenchymal pad (VMP),
      a condensed area of mesenchyme known to induce prostatic organogenesis.
      Characterization of VMP cells (VMPCs) showed that they retained expression of AR
      as well as transcripts for FGF10 and TGFbeta1, -2, and -3. We propose that VMPCs
      are a good model of specialized mesenchyme involved in prostatic organogenesis
      and are distinct from general urogenital sinus mesenchyme/stroma. Treatment of
      VMPCs with TGFbeta1 resulted in a rapid and transient decrease in Fgf10
      transcript levels, which were reduced 9-fold at 3 h. TGFbeta1 also inhibited
      Fgf10 expression in VMP organ rudiments grown in vitro. To further analyze Fgf10
      regulation, 6 kb of mouse genomic sequence 5' to the translation start site was
      characterized by promoter analysis. Deletion analysis of the Fgf10 promoter in
      VMPCs identified a region of the promoter that mediated a significant proportion
      of promoter activity as well as mediating promoter down-regulation by TGFbeta1.
      This element was located between nucleotides -182 and -172 and contained a
      consensus Sp1 binding site. Taken together, our data suggest that TGFbeta1 is a
      regulator of Fgf10 expression in prostatic mesenchyme and that a proximal element
      within the Fgf10 promoter plays an important role in its regulation and
      expression.

PMID- 14726453
TI  - Neonatal herpes simplex infection.
AB  - Tremendous advances have occurred over the past 30 years in the diagnosis and
      management of neonatal herpes simplex virus (HSV) disease. Mortality in patients
      with disseminated disease has decreased from 85 to 29%, and that in patients with
      central nervous system (CNS) disease has decreased from 50 to 4%. Morbidity has
      been improved more modestly: the proportion of patients with disseminated disease
      who are developing normally at 1 year has increased from 50 to 83%. While the
      proportion of patients with neurologic morbidity following CNS disease has
      remained essentially unchanged over the past three decades, the total number of
      patients who are developing normally following HSV CNS disease has increased due
      to the improved survival. Although additional therapeutic advances in the future
      are possible, more immediate methods for further improvements in outcome for
      patients with this potentially devastating disease lie in an enhanced awareness
      of neonatal HSV infection and disease. A thorough understanding of the biology
      and natural history of HSV in the gravid woman and the neonate provides the basis
      for such an index of suspicion and is provided in this article.

PMID- 14726455
TI  - Infection control in cystic fibrosis.
AB  - Over the past 20 years there has been a greater interest in infection control in
      cystic fibrosis (CF) as patient-to-patient transmission of pathogens has been
      increasingly demonstrated in this unique patient population. The CF Foundation
      sponsored a consensus conference to craft recommendations for infection control
      practices for CF care providers. This review provides a summary of the literature
      addressing infection control in CF. Burkholderia cepacia complex, Pseudomonas
      aeruginosa, and Staphylococcus aureus have all been shown to spread between
      patients with CF. Standard precautions, transmission-based precautions including
      contact and droplet precautions, appropriate hand hygiene for health care
      workers, patients, and their families, and care of respiratory tract equipment to
      prevent the transmission of infectious agents serve as the foundations of
      infection control and prevent the acquisition of potential pathogens by patients
      with CF. The respiratory secretions of all CF patients potentially harbor
      clinically and epidemiologically important microorganisms, even if they have not
      yet been detected in cultures from the respiratory tract. CF patients should be
      educated to contain their secretions and maintain a distance of >3 ft from other
      CF patients to avoid the transmission of potential pathogens, even if culture
      results are unavailable or negative. To prevent the acquisition of pathogens from
      respiratory therapy equipment used in health care settings as well as in the
      home, such equipment should be cleaned and disinfected. It will be critical to
      measure the dissemination, implementation, and potential impact of these
      guidelines to monitor changes in practice and reduction in infections.

PMID- 14726456
TI  - Cryptosporidium taxonomy: recent advances and implications for public health.
AB  - There has been an explosion of descriptions of new species of Cryptosporidium
      during the last two decades. This has been accompanied by confusion regarding the
      criteria for species designation, largely because of the lack of distinct
      morphologic differences and strict host specificity among Cryptosporidium spp. A
      review of the biologic species concept, the International Code of Zoological
      Nomenclature (ICZN), and current practices for Cryptosporidium species
      designation calls for the establishment of guidelines for naming Cryptosporidium
      species. All reports of new Cryptosporidium species should include at least four
      basic components: oocyst morphology, natural host specificity, genetic
      characterizations, and compliance with the ICZN. Altogether, 13 Cryptosporidium
      spp. are currently recognized: C. muris, C. andersoni, C. parvum, C. hominis, C.
      wrairi, C. felis, and C. cannis in mammals; C. baileyi, C. meleagridis, and C.
      galli in birds; C. serpentis and C. saurophilum in reptiles; and C. molnari in
      fish. With the establishment of a framework for naming Cryptosporidium species
      and the availability of new taxonomic tools, there should be less confusion
      associated with the taxonomy of the genus Cryptosporidium. The clarification of
      Cryptosporidium taxonomy is also useful for understanding the biology of
      Cryptosporidium spp., assessing the public health significance of Cryptosporidium
      spp. in animals and the environment, characterizing transmission dynamics, and
      tracking infection and contamination sources.

PMID- 14726457
TI  - Health impacts of environmental mycobacteria.
AB  - Environmental mycobacteria are emerging pathogens causing opportunistic
      infections in humans and animals. The health impacts of human-mycobacterial
      interactions are complex and likely much broader than currently recognized.
      Environmental mycobacteria preferentially survive chlorination in municipal
      water, using it as a vector to infect humans. Widespread chlorination of water
      has likely selected more resistant environmental mycobacteria species and
      potentially explains the shift from M. scrofulaceum to M. avium as a cause of
      cervical lymphadenitis in children. Thus, human activities have affected
      mycobacterial ecology. While the slow growth and hydrophobicity of environmental
      mycobacteria appear to be disadvantages, the unique cell wall architecture also
      grants high biocide and antibiotic resistance, while hydrophobicity facilitates
      nutrient acquisition, biofilm formation, and spread by aerosolization. The
      remarkable stress tolerance of environmental mycobacteria is the major reason
      they are human pathogens. Environmental mycobacteria invade protozoans,
      exhibiting parasitic and symbiotic relationships. The molecular mechanisms of
      mycobacterial intracellular pathogenesis in animals likely evolved from similar
      mechanisms facilitating survival in protozoans. In addition to outright
      infection, environmental mycobacteria may also play a role in chronic bowl
      diseases, allergies, immunity to other pulmonary infections, and the efficacy of
      bacillus Calmette-Guerin vaccination.

PMID- 14726454
TI  - Pathogenicity islands in bacterial pathogenesis.
AB  - In this review, we focus on a group of mobile genetic elements designated
      pathogenicity islands (PAI). These elements play a pivotal role in the virulence
      of bacterial pathogens of humans and are also essential for virulence in
      pathogens of animals and plants. Characteristic molecular features of PAI of
      important human pathogens and their role in pathogenesis are described. The
      availability of a large number of genome sequences of pathogenic bacteria and
      their benign relatives currently offers a unique opportunity for the
      identification of novel pathogen-specific genomic islands. However, this
      knowledge has to be complemented by improved model systems for the analysis of
      virulence functions of bacterial pathogens. PAI apparently have been acquired
      during the speciation of pathogens from their nonpathogenic or environmental
      ancestors. The acquisition of PAI not only is an ancient evolutionary event that
      led to the appearance of bacterial pathogens on a timescale of millions of years
      but also may represent a mechanism that contributes to the appearance of new
      pathogens within a human life span. The acquisition of knowledge about PAI, their
      structure, their mobility, and the pathogenicity factors they encode not only is
      helpful in gaining a better understanding of bacterial evolution and interactions
      of pathogens with eukaryotic host cells but also may have important practical
      implications such as providing delivery systems for vaccination, tools for cell
      biology, and tools for the development of new strategies for therapy of bacterial
      infections.

PMID- 14726458
TI  - Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis
      of increasing concern.
AB  - Echinococcosis in humans is a zoonotic infection caused by larval stages
      (metacestodes) of cestode species of the genus Echinococcus. Cystic
      echinococcosis (CE) is caused by Echinococcus granulosus, alveolar echinococcosis
      (AE) is caused by E. multilocularis, and polycystic forms are caused by either E.
      vogeli or E. oligarthrus. In untreated cases, AE has a high mortality rate.
      Although control is essentially feasible, CE remains a considerable health
      problem in many regions of the northern and southern hemispheres. AE is
      restricted to the northern hemisphere regions of North America and Eurasia.
      Recent studies have shown that E. multilocularis, the causative agent of AE, is
      more widely distributed than previously thought. There are also some hints of an
      increasing significance of polycystic forms of the disease, which are restricted
      to Central and South America. Various aspects of human echinococcosis are
      discussed in this review, including data on the infectivity of genetic variants
      of E. granulosus to humans, the increasing invasion of cities in Europe and Japan
      by red foxes, the main definitive hosts of E. multilocularis, and the first
      demonstration of urban cycles of the parasite. Examples of emergence or
      reemergence of CE are presented, and the question of potential spreading of E.
      multilocularis is critically assessed. Furthermore, information is presented on
      new and improved tools for diagnosing the infection in final hosts (dogs, foxes,
      and cats) by coproantigen or DNA detection and the application of molecular
      techniques to epidemiological studies. In the clinical field, the available
      methods for diagnosing human CE and AE are described and the treatment options
      are summarized. The development of new chemotherapeutic options for all forms of
      human echinococcosis remains an urgent requirement. A new option for the control
      of E. granulosus in the intermediate host population (mainly sheep and cattle) is
      vaccination. Attempts are made to reduce the prevalence of E. multilocualaris in
      fox populations by regular baiting with an anthelmintic (praziquantel). Recent
      data have shown that this control option may be used in restricted areas, for
      example in cities, with the aim of reducing the infection risk for humans.

PMID- 14726459
TI  - Global change and human vulnerability to vector-borne diseases.
AB  - Global change includes climate change and climate variability, land use, water
      storage and irrigation, human population growth and urbanization, trade and
      travel, and chemical pollution. Impacts on vector-borne diseases, including
      malaria, dengue fever, infections by other arboviruses, schistosomiasis,
      trypanosomiasis, onchocerciasis, and leishmaniasis are reviewed. While climate
      change is global in nature and poses unknown future risks to humans and natural
      ecosystems, other local changes are occurring more rapidly on a global scale and
      are having significant effects on vector-borne diseases. History is invaluable as
      a pointer to future risks, but direct extrapolation is no longer possible because
      the climate is changing. Researchers are therefore embracing computer simulation
      models and global change scenarios to explore the risks. Credible ranking of the
      extent to which different vector-borne diseases will be affected awaits a
      rigorous analysis. Adaptation to the changes is threatened by the ongoing loss of
      drugs and pesticides due to the selection of resistant strains of pathogens and
      vectors. The vulnerability of communities to the changes in impacts depends on
      their adaptive capacity, which requires both appropriate technology and
      responsive public health systems. The availability of resources in turn depends
      on social stability, economic wealth, and priority allocation of resources to
      public health.

PMID- 14726461
TI  - Strongyloides stercoralis in the Immunocompromised Population.
AB  - Strongyloides stercoralis is an intestinal nematode of humans that infects tens
      of millions of people worldwide. S. stercoralis is unique among intestinal
      nematodes in its ability to complete its life cycle within the host through an
      asexual autoinfective cycle, allowing the infection to persist in the host
      indefinitely. Under some conditions associated with immunocompromise, this
      autoinfective cycle can become amplified into a potentially fatal hyperinfection
      syndrome, characterized by increased numbers of infective filariform larvae in
      stool and sputum and clinical manifestations of the increased parasite burden and
      migration, such as gastrointestinal bleeding and respiratory distress. S.
      stercoralis hyperinfection is often accompanied by sepsis or meningitis with
      enteric organisms. Glucocorticoid treatment and human T-lymphotropic virus type 1
      infection are the two conditions most specifically associated with triggering
      hyperinfection, but cases have been reported in association with hematologic
      malignancy, malnutrition, and AIDS. Anthelmintic agents such as ivermectin have
      been used successfully in treating the hyperinfection syndrome as well as for
      primary and secondary prevention of hyperinfection in patients whose exposure
      history and underlying condition put them at increased risk.

PMID- 14726462
TI  - Staphylococcus aureus capsular polysaccharides.
AB  - Serotype 5 and 8 capsular polysaccharides predominate among clinical isolates of
      Staphylococcus aureus. The results of experiments in animal models of infection
      have revealed that staphylococcal capsules are important in the pathogenesis of
      S. aureus infections. The capsule enhances staphylococcal virulence by impeding
      phagocytosis, resulting in bacterial persistence in the bloodstream of infected
      hosts. S. aureus capsules also promote abscess formation in rats. Although the
      capsule has been shown to modulate S. aureus adherence to endothelial surfaces in
      vitro, animal studies suggest that it also promotes bacterial colonization and
      persistence on mucosal surfaces. S. aureus capsular antigens are surface
      associated, limited in antigenic specificity, and highly conserved among clinical
      isolates. With the emergence of vancomycin-resistant S. aureus in the United
      States in 2002, new strategies are needed to combat staphylococcal infections.
      Purified serotype 5 and 8 capsular polysaccharides offer promise as target
      antigens for a vaccine to prevent staphylococcal infections, although the
      inclusion of other antigens is likely to be essential in the development of an
      effective S. aureus vaccine. The genetics and mechanisms of capsule biosynthesis
      are complex, and much work remains to enhance our understanding of capsule
      biosynthesis and its regulation.

PMID- 14726464
TI  - Urgent clinical need for accurate and precise bilirubin measurements in the
      United States to prevent kernicterus.

PMID- 14726465
TI  - Measurement of plasma free metanephrine and normetanephrine by liquid
      chromatography-tandem mass spectrometry for diagnosis of pheochromocytoma.
AB  - BACKGROUND: Quantification of plasma free metanephrines is usually accomplished
      by HPLC with electrochemical detection, but sample preparation is labor-intensive
      and time-consuming, run times are long, and interfering substances sometimes
      obscure the relevant peaks. The aim of this study was to develop a sensitive and
      specific LC-MS/MS method for plasma free metanephrines. METHODS: After solid
      phase extraction, chromatographic separation of normetanephrine (NMN) and
      metanephrine (MN) was accomplished by use of a cyano analytical column. NMN, MN,
      d(3)-NMN, and d(3)-MN positive ions were detected in the multiple-reaction
      monitoring mode using the specific transitions m/z 166-->134, 180-->148, 169-
      >137, and 183-->151, respectively, with an atmospheric pressure chemical
      ionization source. RESULTS: Multiple calibration curves exhibited consistent
      linearity and reproducibility. Interassay imprecision values (CV; n = 20) for NMN
      at 0.64, 1.9, and 2.7 nmol/L were 6.6%, 7.8%, and 13%, respectively. Interassay
      CV for MN at 0.60, 1.2, and 2.1 nmol/L (n = 20) were 9.2%, 6.8%, and 9.8%,
      respectively. The mean recoveries of NMN and MN relative to the internal standard
      were 100% and 96%, respectively. The assays were linear between 0.20 and 10.0
      nmol/L. Deming regression of HPLC and LC-MS/MS results yielded slopes of 0.93
      (95% confidence interval, 0.89-0.98) and 0.89 (0.85-0.93) and y-intercepts of 
      0.16 and 0.03 nmol/L for NMN (n = 132) and MN (n = 92), respectively.
      CONCLUSIONS: This novel LC-MS/MS approach provides a precise, rapid, and specific
      alternative method to HPLC for the quantification of the low nanomolar
      concentrations of free metanephrines in plasma.

PMID- 14726466
TI  - Evaluation of oligonucleotide arrays for sequencing of the p53 gene in DNA from
      formalin-fixed, paraffin-embedded breast cancer specimens.
AB  - BACKGROUND: Routine tissue processing has generated banks of paraffin-embedded
      tissue that could be used in retrospective cohort studies to study the molecular
      changes that occur during cancer development. The purpose of this study was to
      determine whether a p53 microarray could be used to sequence the p53 gene in DNA
      extracted from formalin-fixed, paraffin-embedded (FFPE) tissues. METHODS: DNA was
      extracted from 70 FFPE breast cancer tissue specimens. p53 was sequenced with an
      oligonucleotide microarray (p53 GeneChip; Affymetrix), and the results were
      compared with the results obtained from direct sequencing. RESULTS: DNA was
      extracted from 62 of 70 cases. We identified 26 mutations in 24 of the 62 cases
      by the p53 GeneChip. No polymorphisms were detected, and exon 4 could not be
      evaluated in 20 cases. There were 43 genetic alterations detected by direct
      sequencing in 35 of the 62 cases. These consisted of 26 polymorphisms and 17
      mutations in exons or splice sites. Fifteen mutations were identified by both
      methods. Direct sequencing detected significantly more gene alterations (43 of
      54) in DNA extracted from FFPE tissue than the p53 GeneChip (26 of 54; P =
      0.018). However, if the changes in exon 4 were eliminated from this comparison,
      the p53 GeneChip detected 26 of 27 mutations compared with direct sequencing,
      which identified 16 of 27 mutations. (P = 0.016). CONCLUSIONS: A combination of
      oligonucleotide microarray and direct sequencing may be necessary to accurately
      identify p53 gene alterations in FFPE breast cancer. The p53 GeneChip cannot be
      used to detect exon 4 polymorphisms (codon 72) in FFPE breast cancer tissue.

PMID- 14726467
TI  - High preoperative CA 15-3 concentrations predict adverse outcome in node-negative
      and node-positive breast cancer: study of 600 patients with histologically
      confirmed breast cancer.
AB  - BACKGROUND: CA 15-3 is the most widely used serum marker in breast cancer.
      Currently, its main uses are in the surveillance of patients with diagnosed
      disease and monitoring the treatment of patients with advanced disease. METHODS:
      Preoperative CA 15-3 concentrations were measured prospectively in 600 patients
      with histologically confirmed breast cancer. Marker concentrations were related
      to patient outcome by both univariate and multivariate analysis. RESULTS: After a
      median follow-up of 6.27 years, patients with high preoperative concentrations of
      CA 15-3 (>30 units/L) had a significantly shorter overall survival pattern than
      those with low concentrations. As a prognostic factor, CA 15-3 was independent of
      tumor size, axillary node status, and patient age. As well as being prognostic in
      the total population of patients, CA 15-3 also predicted outcome in different
      subgroups of patients, including those with both node-negative and node-positive
      disease, those who were both estrogen receptor (ER)-negative and ER-positive, and
      those younger and older that 50 years of age. CA 15-3 was also predictive of
      outcome irrespective of the type of adjuvant therapy administered, i.e., whether
      adjuvant hormone therapy, adjuvant chemotherapy, or radiotherapy was
      administered. CONCLUSION: Assay of CA 15-3 is a relatively inexpensive,
      convenient, and noninvasive method for evaluating prognosis in newly diagnosed
      breast cancer patients.

PMID- 14726463
TI  - History, dynamics, and public health importance of malaria parasite resistance.
AB  - Despite considerable efforts, malaria is still one of the most devastating
      infectious diseases in the tropics. The rapid spread of antimalarial drug
      resistance currently compounds this grim picture. In this paper, we review the
      history of antimalarial drug resistance and the methods for monitoring it and
      assess the current magnitude and burden of parasite resistance to two commonly
      used drugs: chloroquine and sulfadoxine-pyrimethamine. Furthermore, we review the
      factors involved in the emergence and spread of drug resistance and highlight its
      public health importance. Finally, we discuss ways of dealing with such a problem
      by using combination therapy and suggest some of the research themes needing
      urgent answers.

PMID- 14726468
TI  - In vitro contamination of hair by marijuana smoke.
AB  - BACKGROUND: The deposition of cannabinoids on/into hair from environmental smoke
      can be considered as a potential source of drug findings in hair. We studied
      external uptake of cannabinoids from marijuana smoke, investigating possible
      influencing factors on drug uptake and the efficiency of decontamination
      procedures. METHODS: Strands of a natural hair sample were moistened with water,
      greased with sebum or sebum/sweat, or bleached or permed. Treated and untreated
      samples were exposed to marijuana smoke for 60 min. Aliquots of each hair strand
      were either kept unwashed or were washed with methanol, dichloromethane, or 5 g/L
      dodecyl sulfate in water. Cannabinoid concentrations in unwashed and washed hair
      samples, as well as in air samples collected from the exposure chamber and in the
      marijuana sample being combusted, were quantified by gas chromatography-mass
      spectrometry or gas chromatography. RESULTS: Cannabinoids were deposited on the
      hair fibers from marijuana smoke. Cannabinoid concentrations were dependent on
      air concentration and hair pretreatment. Uptake was less in untreated than in
      pretreated hair. Concentrations were increased in damp hair, but were even higher
      in greased hair. There was no significant difference in concentration between
      bleached and permed strands. External contaminants were completely removed by
      washing with methanol and dichloromethane in untreated hair only. Washing with
      dodecyl sulfate in water was insufficient in all cases. CONCLUSIONS: Exposures of
      hair to marijuana smoke yields detectable cannabinoids depending on
      concentrations in the air, hair care habits, and cosmetic treatment.
      Environmental marijuana smoke exposure may produce false-positive or falsely
      increased test results in hair.

PMID- 14726460
TI  - Theiler's virus infection: a model for multiple sclerosis.
AB  - Both genetic background and environmental factors, very probably viruses, appear
      to play a role in the etiology of multiple sclerosis (MS). Lessons from viral
      experimental models suggest that many different viruses may trigger inflammatory
      demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in
      susceptible strains of mice early acute disease resembling encephalomyelitis
      followed by late chronic demyelinating disease, which is one of the best, if not
      the best, animal model for MS. During early acute disease the virus replicates in
      gray matter of the central nervous system but is eliminated to very low titers 2
      weeks postinfection. Late chronic demyelinating disease becomes clinically
      apparent approximately 2 weeks later and is characterized by extensive
      demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord
      atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is
      not clear whether it is due to molecular mimicry or epitope spreading. Cytokines,
      nitric oxide/reactive nitrogen species, and costimulatory molecules are involved
      in the pathogenesis of both diseases. Close similarities between Theiler's virus
      induced demyelinating disease in mice and MS in humans, include the following:
      major histocompatibility complex-dependent susceptibility; substantial
      similarities in neuropathology, including axonal damage and remyelination; and
      paucity of T-cell apoptosis in demyelinating disease. Both diseases are
      immunologically mediated. These common features emphasize the close similarities
      of Theiler's virus-induced demyelinating disease in mice and MS in humans.

PMID- 14726469
TI  - Properties of the reverse transcription reaction in mRNA quantification.
AB  - BACKGROUND: In most measurements of gene expression, mRNA is first reverse
      transcribed into cDNA. We studied the reverse transcription reaction and its
      consequences for quantitative measurements of gene expression. METHODS: We used
      SYBR green I-based quantitative real-time PCR (QPCR) to measure the properties of
      reverse transcription reaction for the beta-tubulin, glyceraldehyde-3-phosphate
      dehydrogenase, Glut2, CaV1D, and insulin II genes, using random hexamers,
      oligo(dT), and gene-specific reverse transcription primers. RESULTS: Experimental
      variation in reverse transcription-QPCR (RT-QPCR) was mainly attributable to the
      reverse transcription step. Reverse transcription efficiency depended on priming
      strategy, and the dependence was different for the five genes studied. Reverse
      transcription yields also depended on total RNA concentration. CONCLUSIONS: RT
      QPCR gene expression measurements are comparable only when the same priming
      strategy and reaction conditions are used in all experiments and the samples
      contain the same total amount of RNA. Experimental accuracy is improved by
      running samples in (at least) duplicate starting with the reverse transcription
      reaction.

PMID- 14726471
TI  - Mass spectrometric phenotyping of Val34Leu polymorphism of blood coagulation
      factor XIII by differential peptide display.
AB  - BACKGROUND: The Val34Leu mutation in the activation peptide of factor XIII
      (FXIIIA) correlates with a lower incidence of myocardial infarction and ischemic
      stroke but an increased risk for hemorrhagic stroke. We describe mass
      spectrometric detection of the activation peptide variants in human serum.
      METHODS: We used differential peptide display (DPD) to compare comprehensive
      peptide maps from pairs of serum samples from healthy volunteers. Peptides were
      separated by liquid chromatography, and fractions were subjected to mass
      spectrometry. Mass spectra of all fractions were combined, giving a peptide map
      representing a two-dimensional display of peptide masses. After comparison of
      peptide mass maps, peptides that differentiated FXIIIA phenotypes were identified
      by mass spectrometry. RESULTS: Val34Leu polymorphisms of the activation peptide
      of FXIIIA were identified in 20 serum samples from 10 volunteers by DPD, and
      their sequences were confirmed by nanoelectrospray-ionization quadrupole time-of
      flight mass spectrometry. Analysis of three (V34V, V34L, and L34L) phenotypes was
      confirmed by allele-specific genotypic analysis in all (n = 10) volunteers.
      CONCLUSION: DPD provides a simple and easy-to-use phenotype assay with advantages
      over PCR-based assays in being faster and directly analyzing the compound of
      interest.

PMID- 14726470
TI  - Differential gene expression of Eph receptors and ephrins in benign human tissues
      and cancers.
AB  - BACKGROUND: Eph receptors and their ligands, the ephrins, represent a large class
      of cell-cell communication molecules with well-defined developmental functions.
      Their role in healthy adult tissues and in human disease is still largely
      unknown, although diverse roles in carcinogenesis have been postulated. METHODS:
      We established a set of fluorescent PCR probes and primers for the definition of
      individual gene expression profiles of 12 different Eph receptors and 8 ephrins
      in 13 different healthy tissues. The mRNA expression profiles were studied in
      human lung, colorectal, kidney, liver, and brain cancers. RESULTS: The family of
      Eph receptors/ephrins was widely expressed in adult tissues with organ-site
      specific patterns: EphB6 was highest in the thymus, compatible with an
      involvement in T-cell maturation. Brain and testis shared a unique pattern with
      EphA6, EphA8, and EphB1 being the most prominent. EphA7 had a high abundance in
      the kidney vasculature. Ephrin-A3 was up-regulated 26-fold in lung cancer, and
      EphB2 was up-regulated 9-fold in hepatocellular carcinoma. EphA8 was down
      regulated in colon cancer, and EphA1/EphA8 was down-regulated in glioblastomas.
      CONCLUSION: Eph/Ephrin genes are widely expressed in all adult organs with
      certain organ-site-specific patterns. Because their function in adult tissues
      remains unknown, further analysis of their role in disease may disclose new
      insights beyond their well-defined meaning in development.

PMID- 14726472
TI  - Association of serum carotenoids and tocopherols with gamma-glutamyltransferase:
      the Cardiovascular Risk Development in Young Adults (CARDIA) Study.
AB  - BACKGROUND: Our previous studies suggest that serum gamma-glutamyltransferase
      (GGT) activity may be related to oxidative stress, supporting findings of
      experimental studies. To further examine the role of GGT in relation to oxidative
      stress, we investigated the association between serum carotenoids and
      tocopherols, which have antioxidant properties, and serum GGT. METHODS: Study
      participants were 3128 black and white men and women 17-35 years of age in 1985
      1986. Serum carotenoids and tocopherols were measured at years 0 and 7, and serum
      GGT was measured at years 0 and 10. RESULTS: Circulating concentrations of alpha
      carotene, beta-carotene, and beta-cryptoxanthin inversely predicted the serum GGT
      concentration measured 10 years later in a dose-response manner (P for trend
      <0.01). Year 0 zeaxanthin/lutein was weakly inversely associated with year 10 GGT
      (P for trend = 0.08), and year 0 lycopene was unrelated to year 10 GGT. Adjusted
      geometric means of serum GGT at year 10 according to quintile of the sum of four
      carotenoids at year 0 (alpha-carotene, beta-carotene, beta-cryptoxanthin, and
      zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01).
      Year 0 alpha-tocopherol was also a significant inverse predictor of year 10 serum
      GGT concentration (P for trend = 0.03), whereas gamma-tocopherol showed an
      inconsistent or possibly U-shaped association. However, year 0 serum GGT did not
      predict serum antioxidants measured 7 years later. CONCLUSION: Our present
      findings support the contention that serum GGT concentration is a marker related
      with oxidative stress.

PMID- 14726473
TI  - Association of coronary heart disease with pre-beta-HDL concentrations in
      Japanese men.
AB  - BACKGROUND: In individuals heterozygous for ABCA1 transporter mutations,
      defective reverse cholesterol transport (RCT) causes low HDL-cholesterol and
      premature coronary heart disease (CHD). However, the extent to which impaired RCT
      underlies premature CHD in others with low HDL-cholesterol is not known. The
      primary acceptors of cell cholesterol are a minor subclass of lipid-poor pre-beta
      HDLs. These are generated during remodeling of alpha-HDLs, which account for
      almost all HDL-cholesterol. We studied the strength of the association of CHD
      with pre-beta-HDL concentrations in Japanese men. METHODS: Blood was collected
      from 42 men with clinical CHD and 44 healthy controls 40-70 years of age. Pre
      beta-HDL was assayed by crossed immunoelectrophoresis. RESULTS: Cases had lower
      HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-beta-HDL (-55%;
      all P <0.001) concentrations; lower pre-beta-HDL:alpha-HDL ratios (-45%; P
      <0.001); and higher plasma triglycerides (20%; P <0.03) than the controls. On
      stepwise logistic regression, CHD was associated most strongly with pre-beta-HDL
      concentrations. On ROC analysis, pre-beta-HDL concentration discriminated between
      cases and controls better than any other lipoprotein measurement. When plasma was
      incubated for 16 h at 37 degrees C, mean (SD) pre-beta-HDL increased by 47 (36)%
      in controls, but was unchanged in cases (group difference, P <0.001).
      CONCLUSIONS: Our results suggest that inefficient RCT, secondary to a low pre
      beta-HDL concentration and production rate in plasma, contributes to premature
      CHD in Japanese men with low HDL-cholesterol.

PMID- 14726474
TI  - B-type natriuretic peptide exerts broad functional opposition to transforming
      growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast
      conversion, proliferation, and inflammation.
AB  - The natriuretic peptides, including human B-type natriuretic peptide (BNP), have
      been implicated in the regulation of cardiac remodeling. Because transforming
      growth factor-beta (TGF-beta) is associated with profibrotic processes in heart
      failure, we tested whether BNP could inhibit TGF-beta-induced effects on primary
      human cardiac fibroblasts. BNP inhibited TGF-beta-induced cell proliferation as
      well as the production of collagen 1 and fibronectin proteins as measured by
      Western blot analysis. cDNA microarray analysis was performed on RNA from cardiac
      fibroblasts incubated in the presence or absence of TGF-beta and BNP for 24 and
      48 hours. TGF-beta, but not BNP, treatment resulted in a significant change in
      the RNA profile. BNP treatment resulted in a remarkable reduction in TGF-beta
      effects; 88% and 85% of all TGF-beta-regulated mRNAs were affected at 24 and 48
      hours, respectively. BNP opposed TGF-beta-regulated genes related to fibrosis
      (collagen 1, fibronectin, CTGF, PAI-1, and TIMP3), myofibroblast conversion
      (alpha-smooth muscle actin 2 and nonmuscle myosin heavy chain), proliferation
      (PDGFA, IGF1, FGF18, and IGFBP10), and inflammation (COX2, IL6, TNFalpha-induced
      protein 6, and TNF superfamily, member 4). Lastly, BNP stimulated the
      extracellular signal-related kinase pathway via cyclic guanosine monophosphate
      dependent protein kinase signaling, and two mitogen-activated protein kinase
      kinase inhibitors, U0126 and PD98059, reversed BNP inhibition of TGF-beta-induced
      collagen-1 expression. These findings demonstrate that BNP has a direct effect on
      cardiac fibroblasts to inhibit fibrotic responses via extracellular signal
      related kinase signaling, suggesting that BNP functions as an antifibrotic factor
      in the heart to prevent cardiac remodeling in pathological conditions.

PMID- 14726475
TI  - Cardiac-specific induction of the transcriptional coactivator peroxisome
      proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial
      biogenesis and reversible cardiomyopathy in a developmental stage-dependent
      manner.
AB  - Recent evidence has identified the peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) as a regulator of cardiac energy metabolism
      and mitochondrial biogenesis. We describe the development of a transgenic system
      that permits inducible, cardiac-specific overexpression of PGC-1alpha. Expression
      of the PGC-1alpha transgene in this system (tet-on PGC-1alpha) is cardiac
      specific in the presence of doxycycline (dox) and is not leaky in the absence of
      dox. Overexpression of PGC-1alpha in tet-on PGC-1alpha mice during the neonatal
      stages leads to a dramatic increase in cardiac mitochondrial number and size
      coincident with upregulation of gene markers associated with mitochondrial
      biogenesis. In contrast, overexpression of PGC-1alpha in the hearts of adult mice
      leads to a modest increase in mitochondrial number, derangements of mitochondrial
      ultrastructure, and development of cardiomyopathy. The cardiomyopathy in adult
      tet-on PGC-1alpha mice is characterized by an increase in ventricular mass and
      chamber dilatation. Surprisingly, removal of dox and cessation of PGC-1alpha
      overexpression in adult mice results in complete reversal of cardiac dysfunction
      within 4 weeks. These results indicate that PGC-1alpha drives mitochondrial
      biogenesis in a developmental stage-dependent manner permissive during the
      neonatal period. This unique murine model should prove useful for the study of
      the molecular regulatory programs governing mitochondrial biogenesis and
      characterization of the relationship between mitochondrial dysfunction and
      cardiomyopathy and as a general model of inducible, reversible cardiomyopathy.

PMID- 14726476
TI  - Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth
      factor-1 overexpression.
AB  - To determine whether cellular aging leads to a cardiomyopathy and heart failure,
      markers of cellular senescence, cell death, telomerase activity, telomere
      integrity, and cell regeneration were measured in myocytes of aging wild-type
      mice (WT). These parameters were similarly studied in insulin-like growth factor
      1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival
      and may delay cellular aging. Importantly, the consequences of aging on cardiac
      stem cell (CSC) growth and senescence were evaluated. Gene products implicated in
      growth arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were
      detected in myocytes of young WT mice, and their expression increased with age.
      IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity
      decreased in aging WT myocytes but increased in TG, paralleling the changes in
      Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in
      telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs
      increased with age in WT impairing the growth and turnover of cells in the heart.
      DNA damage and myocyte death exceeded cell formation in old WT, leading to a
      decreased number of myocytes and heart failure. This did not occur in TG in which
      CSC-mediated myocyte regeneration compensated for the extent of cell death
      preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and
      telomerase delaying cellular aging and death. The differential response of TG
      mice to chronological age may result from preservation of functional CSCs
      undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes
      conditions the development of an aging myopathy.

PMID- 14726477
TI  - Frequency- and afterload-dependent cardiac modulation in vivo by troponin I with
      constitutively active protein kinase A phosphorylation sites.
AB  - Acute beta-adrenergic stimulation enhances cardiac contractility, accelerates
      muscle relaxation, and amplifies the inotropic and lusitropic response to
      increased stimulation frequency. These effects are modulated by phosphorylation
      of calcium handling and myofilament proteins such as troponin I (TnI) by protein
      kinase A (PKA). To more directly delineate the role of TnI PKA phosphorylation,
      transgenic mice were generated that overexpress cardiac TnI in which the serine
      residues normally targeted by PKA are mutated to aspartic acid to mimic
      constitutive phosphorylation (TnIDD22,23). Native cardiac TnI was near completely
      replaced in one transgenic line as assessed by in vitro phosphorylation, and this
      led to reduced calcium sensitivity of myofibrillar MgATPase, as expected.
      TnIDD22,23 mice had mildly enhanced basal systolic and diastolic function, and
      displayed marked augmentation of frequency-dependent inotropy and relaxation,
      with a peak frequency response 2-fold greater in mutants than controls (P<0.005).
      Increasing afterload prolonged relaxation more in nontransgenic than TnIDD22,23
      (P<0.02), whereas contractile responses to afterload were similar between these
      strains. Isoproterenol treatment eliminated the differential force-frequency and
      afterload response between TnIDD22,23 and controls. In contrast to in vivo
      studies, isolated isometric trabeculae from nontransgenic and TnIDD22,23 mice had
      similar basal, isoproterenol-, and frequency-stimulated function, suggesting that
      muscle shortening may be important to TnI PKA effects. These results support a
      novel role for cardiac TnI PKA phosphorylation in the rate-dependent enhancement
      of systolic and diastolic function in vivo and afterload sensitivity of
      relaxation. These results have implications for cardiac failure in which force
      frequency modulation is blunted and afterload relaxation sensitivity increased in
      association with diminished PKA TnI phosphorylation.

PMID- 14726478
TI  - The pathology of experience.

PMID- 14726482
TI  - Stereoselective excision of thymine glycol from oxidatively damaged DNA.
AB  - DNA damage created by reactive oxygen species includes the prototypic oxidized
      pyrimidine, thymine glycol (Tg), which exists in oxidatively damaged DNA as two
      diastereoisomeric pairs. In Escherichia coli, Saccharomyces cerevesiae and mice,
      Tg is preferentially excised by endonuclease III (Endo III) and endonuclease VIII
      (Endo VIII), yNTG1 and yNTG2, and mNTH and mNEIL1, respectively. We have explored
      the ability of these DNA glycosylases to discriminate between Tg stereoisomers.
      Oligonucleotides containing a single, chromatographically pure (5S,6R) or (5R,6S)
      stereoisomer of Tg were prepared by oxidation with osmium tetroxide. Steady-state
      kinetic analyses of the excision process revealed that Endo III, Endo VIII,
      yNTG1, mNTH and mNEIL1, but not yNTG2, excise Tg isomers from DNA in a
      stereoselective manner, as reflected in the parameter of catalytic efficiency
      (kcat/Km). When DNA glycosylases occur as complementary pairs, failure of one or
      both enzymes to excise their cognate Tg stereoisomer from oxidatively damaged DNA
      could have deleterious consequences for the cell.

PMID- 14726483
TI  - Nuclear antisense effects in cyclophilin A pre-mRNA splicing by oligonucleotides:
      a comparison of tricyclo-DNA with LNA.
AB  - The nuclear antisense properties of a series of tricyclo (tc)-DNA oligonucleotide
      9-15mers, targeted against the 3' and 5' splice sites of exon 4 of cyclophilin A
      (CyPA) pre-mRNA, were evaluated in HeLa cells and compared with those of
      corresponding LNA-oligonucleotides. While the 9mers showed no significant
      antisense effect, the 11-15mers induced exon 4 skipping and exon 3+4 double
      skipping to about an equal extent upon lipofectamine mediated transfection in a
      sequence- and dose-dependent manner, as revealed by a RT-PCR assay. The antisense
      efficacy of the tc-oligonucleotides was found to be superior to that of the LNA
      oligonucleotides in all cases by a factor of at least 4-5. A tc-oligonucleotide
      15mer completely abolished CyPA mRNA production at 0.2 microM concentration. The
      antisense effect was confirmed by western blot analysis which revealed a
      reduction in CyPA protein to 13% of its normal level. Fluorescence microscopic
      investigations with a fluorescein labeled tc-15mer revealed a strong propensity
      for homogeneous nuclear localization of this backbone type after lipofectamine
      mediated transfection, while the corresponding lna 15mer showed a less clear
      cellular distribution pattern. Transfection without lipid carrier showed no
      significant internalization of both tc- and LNA- oligonucleotides. The obtained
      results confirm the power of tc-DNA for nuclear antisense applications. Moreover,
      CyPA may become an interesting therapeutic target due to its important role in
      the early steps of the viral replication of HIV-1.

PMID- 14726484
TI  - Triplex-forming oligonucleotide target sequences in the human genome.
AB  - The existence of sequences in the human genome which can be a target for triplex
      formation, and accordingly are candidates for anti-gene therapies, has been
      studied by using bioinformatics tools. It was found that the population of
      triplex-forming oligonucleotide target sequences (TTS) is much more abundant than
      that expected from simple random models. The population of TTS is large in all
      the genome, without major differences between chromosomes. A wide analysis along
      annotated regions of the genome allows us to demonstrate that the largest
      relative concentration of TTS is found in regulatory regions, especially in
      promoter zones, which suggests a tremendous potentiality for triplex strategy in
      the control of gene expression. The dependence of the stability and selectivity
      of the triplexes on the length of the TTS is also analysed using knowledge-based
      rules.

PMID- 14726486
TI  - Tpit-independent function of NeuroD1(BETA2) in pituitary corticotroph
      differentiation.
AB  - NeuroD1(BETA2) and Tpit are cell-specific activators of pituitary
      proopiomelanocortin (POMC) gene transcription. Expression of both factors
      slightly precedes that of POMC at embryonic d 12.5 of mouse pituitary
      development. We now report that NeuroD1(BETA2) is required for early corticotroph
      differentiation. In agreement with the transcriptional synergism observed between
      Tpit and basic helix-loop-helix dimers containing NeuroD1(BETA2), POMC expression
      is delayed in NeuroD1-deficient mice. However, this differentiation defect does
      not reflect a change of corticotroph commitment as revealed by Tpit expression.
      The delay of corticotroph terminal differentiation is transient and coincides
      with the developmental window of NeuroD1 expression in corticotrophs. In contrast
      to their requirement in other NeuroD1-expressing cells, the neurogenin genes do
      not appear to be necessary for corticotroph differentiation. Taken together with
      a similar requirement of Tpit for corticotroph differentiation but not for
      commitment, the present data indicate that the POMC promoter is a point of
      convergence for independent corticotroph differentiating signals.

PMID- 14726487
TI  - Distinct components of Janus kinase/signal transducer and activator of
      transcription signaling pathway mediate the regulation of systemic and tissue
      localized renin-angiotensin system.
AB  - In an attempt to demonstrate the linkage between the Janus kinase (Jak)/signal
      transducer and activator of transcription (STAT) signaling and the activity of
      the systemic or local renin-angiotensin system in vivo, we produced transgenic
      mice harboring angiotensinogen (ANG) promoter containing the wild-type or mutant
      STAT target site (St-domain) fused to the luciferase reporter. The ANG-promoter
      driven luciferase expression was dependent upon phosphorylation of Jak2, as
      administration of tyrphostin AG490, a potent inhibitor of Jak2, down-regulated
      the ANG promoter activity and abolished the stimulated endogenous ANG mRNA level
      in the liver. Administration of angiotensin II peptide to the mice resulted in
      prominent expression of luciferase in the liver and heart of animals containing
      wild type St-domain, but not in transgenes with mutant St-domain. Angiotensin II
      induced signaling caused activation of STAT proteins in the liver (systemic), the
      pattern of which was distinct from that in the heart (local). The inducible
      expression of ANG promoter appears to be mediated by physical association of p300
      with STAT 5B in liver and STAT 3 and STAT 5A in heart. Taken together, these
      results point to the differences in signaling mechanisms in the circulating and
      localized renin-angiotensin system and identify at least two molecular steps, the
      tyrosyl phosphorylation of Jak2 and the STAT/St-domain interaction, as pivotal in
      the regulation of ANG gene transcription.

PMID- 14726488
TI  - Temporal and spatial changes in transcription factor binding and histone
      modifications at the steroidogenic acute regulatory protein (stAR) locus
      associated with stAR transcription.
AB  - We investigated the binding of transcription factors and histone modifications
      associated with expression of the steroidogenic acute regulatory protein (StAR)
      gene in cultured MA-10 Leydig cells and in granulosa cells isolated from mouse
      periovulatory follicles before and after in vivo human chorionic gonadotropin
      administration. Quantitative chromatin immunoprecipitation assays were employed
      to prove association of specific transcription factors (GATA-4, steroidogenic
      factor 1/adrenal-4 binding protein, CCAAT/enhancer-binding protein beta, cAMP
      response element binding protein/cAMP response element modulator) and a
      coactivator (cAMP response element binding protein-binding protein) with the
      promoter, to define patterns of binding to test hypotheses regarding interactions
      among these factors, and to correlate changes in histone modification at the StAR
      locus with transcription. Although each of the transcription factors bound to the
      StAR proximal promoter, we observed cell-specific binding patterns for individual
      factors. From these findings we infer that associations among some of the factors
      can be more complex than can be explained by simple models of stable protein
      protein interactions. Histone modifications were also found to exhibit cell
      specific, temporal and spatial differences across the StAR locus. In MA-10 cells,
      these modifications included increased acetylation of histone H3, increased
      dimethylation of lysine 4 on histone H3 in exonic/intronic sequences (a
      modification that marks transcriptionally permissive chromatin), and reduced
      dimethylation of lysine 9 on histone H3 (a modification linked with gene
      silencing). In mouse granulosa cells, we observed no change in histone H3 or H4
      acetylation, but a rapid loss of the dimethyl K9 histone H3 mark. Our findings
      demonstrate that increased StAR transcription can occur in the context of
      different patterns of transcription factor binding and histone modification.

PMID- 14726489
TI  - Effect of cellular environment on the selective activation of the vitamin D
      receptor by 1alpha,25-dihydroxyvitamin D3 and its analog 1alpha-fluoro-16-ene-20
      epi-23-ene-26,27-bishomo-25-hydroxyvitamin D3 (Ro-26-9228).
AB  - The vitamin D analog, 1alpha-fluoro-16-ene-20-epi-23-ene-26,27-bishomo-25
      hydroxyvitamin D(3) (Ro-26-9228) is tissue selective, with a gene regulation
      preference for bone over duodenum in vivo. In the human osteoblast-like cells,
      hFOB, the vitamin D receptor (VDR)-mediated transcriptional potencies of Ro-26
      9228 and 1,25-dihydroxyvitamin D(3) (1,25D(3)) were similar, but in the
      intestinal cells, Caco-2, transcriptional potency of Ro-26-9228 was 10-50 times
      lower. We hypothesized that transcriptional activation of the VDR by Ro-26-9228
      in the two cell types is regulated differently, and compared VDR extracted from
      hFOB or Caco-2 cells for their abilities to interact with a p160 coactivator
      [glucocorticoid receptor-interacting protein (GRIP)] and with retinoid X receptor
      (RXR) by pull-down assays. 1,25D(3) had similar potencies to induce interactions
      of VDR from the two cell types with these partners of transcription. In contrast,
      Ro-26-9228 induced interaction of osteoblastic VDR with RXR and GRIP but did not
      induce these interactions with VDR from Caco-2 cells. Further studies revealed
      that in hFOB cells the unoccupied VDR was cytoplasmic and proteasome sensitive,
      and that ligand treatment caused a rapid accumulation of the VDR in the
      chromatin. Both cytoplasmic and chromatin-associated ligand-bound VDR from hFOB
      cells had the abilities to interact with GRIP. In contrast, in Caco-2 cells,
      unoccupied VDR was localized in both the cytoplasm (70%) and the chromatin (30%).
      In Caco-2 cells, the cytoplasmic VDR was proteasome resistant, and neither
      1,25D(3) nor Ro-26-9228 induced its binding to GRIP. Only a small fraction of the
      chromatin-associated VDR was proteasome sensitive, and this fraction was
      distinguishable by a faster electrophoretic mobility. 1,25D(3) induced an
      accumulation of the proteasome-sensitive VDR in the chromatin of Caco-2 cells and
      binding to GRIP. Ro-26-9228 failed to induce accumulation of the proteasome
      sensitive VDR in the chromatin or binding to GRIP, but a coincubation of Caco-2
      cells with the analog and a proteasome inhibitor restored these abilities. These
      results suggest that Ro-26-9228 has poor ability to promote the accumulation of a
      proteasome-sensitive, transcriptionally active VDR isoform in Caco-2 cells,
      whereas it does not have this limitation in hFOB cells.

PMID- 14726490
TI  - Differential requirement for steroidogenic factor-1 gene dosage in adrenal
      development versus endocrine function.
AB  - The importance of steroidogenic factor-1 (SF-1) gene dosage in endocrine function
      is evidenced by phenotypes associated with the heterozygous state in mice and
      humans. Here we examined mechanisms underlying SF-1 haploinsufficiency and found
      a striking reduction (12-fold) in SF-1 heterozygous (+/-) adrenocortical size at
      embryonic day (E) 12. Loss of one SF-1 allele led to a selective decrease in
      adrenal precursors within the adrenogonadal primordium at E10.0, without
      affecting the number of gonadal precursors, as marked by GATA-4. Beginning at
      E13.5, increased cell proliferation in SF-1 +/- adrenals allows these organs to
      approach but not attain a normal size. Remarkably, neural crest-derived
      adrenomedullary precursors migrated normally in SF-1 +/- and null embryos.
      However, later in development, medullary growth was compromised in both
      genotypes. Despite the small adrenal size in SF-1heterozygotes, an unexpected
      elevation in steroidogenic capacity per cell was observed in primary adult
      adrenocortical SF-1 +/- cells compared with wild-type cells. Elevated cellular
      steroid output is consistent with the up-regulation of some SF-1 target genes in
      SF-1 +/- adrenals and may partially be due to an observed increase in nerve
      growth factor-induced-B. Our findings underscore the need for full SF-1 gene
      dosage early in adrenal development, but not in the adult adrenal, where
      compensatory mechanisms restore near normal function.

PMID- 14726491
TI  - Trans-activation of mutant follicle-stimulating hormone receptors selectively
      generates only one of two hormone signals.
AB  - Previously, we reported that a liganded LH receptor (LHR) is capable of
      activating itself (cis-activation) and other nonliganded LHRs to induce cAMP
      (trans-activation). Trans-activation of the LHR raises two crucial questions. Is
      trans-activation unique to LHR or common to other G protein-coupled receptors?
      Does trans-activation stimulate phospholipase Cbeta as it does adenylyl cyclase?
      To address these questions, two types of novel FSH receptors (FSHRs) were
      constructed, one defective in hormone binding and the other defective in signal
      generation. The FSHR, a G protein-coupled receptor, comprises two major domains,
      the N-terminal extracellular exodomain that binds the hormone and the membrane
      associated endodomain that generates the hormone signals. For signal defective
      receptors, the exodomain was attached to glycosyl phosphatidylinositol (ExoGPI)
      or the transmembrane domain of CD8 immune receptor (ExoCD). ExoGPI and ExoCD can
      trans-activate another nonliganded FSH. Surprisingly, the trans-activation
      generates a signal to activate either adenylyl cyclase or phospholipase Cbeta,
      but not both. These results indicate that trans-activation in these mutant
      receptors is selective and limited in signal generation, thus providing new
      approaches to investigating the generation of different hormone signals and a
      novel means to selectively generate a particular hormone signal. Our data also
      suggest that the FSHR's exodomain could not trans-activate LHR.

PMID- 14726492
TI  - Accurate qualitative and quantitative proteomic analysis of clinical
      hepatocellular carcinoma using laser capture microdissection coupled with isotope
      coded affinity tag and two-dimensional liquid chromatography mass spectrometry.
AB  - Laser capture microdissection (LCM) is a powerful tool that enables the isolation
      of specific cell types from tissue sections, overcoming the problem of tissue
      heterogeneity and contamination. This study combined the LCM with isotope-coded
      affinity tag (ICAT) technology and two-dimensional liquid chromatography to
      investigate the qualitative and quantitative proteomes of hepatocellular
      carcinoma (HCC). The effects of three different histochemical stains on tissue
      sections have been compared, and toluidine blue stain was proved as the most
      suitable stain for LCM followed by proteomic analysis. The solubilized proteins
      from microdissected HCC and non-HCC hepatocytes were qualitatively and
      quantitatively analyzed with two-dimensional liquid chromatography tandem mass
      spectrometry (2D-LC-MS/MS) alone or coupled with cleavable ICAT labeling
      technology. A total of 644 proteins were qualitative identified, and 261 proteins
      were unambiguously quantitated. These results show that the clinical proteomic
      method using LCM coupled with ICAT and 2D-LC-MS/MS can carry out not only large
      scale but also accurate qualitative and quantitative analysis.

PMID- 14726493
TI  - Isotope-coded affinity tag approach to identify and quantify oxidant-sensitive
      protein thiols.
AB  - An approach is described for identifying and quantifying oxidant-sensitive
      protein thiols using a cysteine-specific, acid-cleavable isotope-coded affinity
      tag (ICAT) reagent (Applied Biosystems, Foster City, CA). The approach is based
      on the fact that only free cysteine thiols are susceptible to labeling by the
      iodoacetamide-based ICAT reagent, and that mass spectrometry can be used to
      quantitate the relative labeling of free thiols. To validate our approach,
      creatine kinase with four cysteine residues, one of which is oxidant-sensitive,
      was chosen as an experimental model. ICAT-labeled peptides derived from creatine
      kinase were used to evaluate the relative abundance of the free thiols in samples
      subjected (or not) to treatment with hydrogen peroxide. As predicted, hydrogen
      peroxide decreased the relative abundance of the unmodified oxidant-sensitive
      thiol residue of cysteine-283 in creatine kinase, providing proof of principle
      that an ICAT-based quantitative mass spectrometry approach can be used to
      identify and quantify oxidation of cysteine thiols. This approach opens an avenue
      for proteomics studies of the redox state of protein thiols.

PMID- 14726494
TI  - Regulation of TLR signaling and inflammation by SOCS family proteins.
AB  - Immune and inflammatory systems are controlled by multiple cytokines, including
      interleukins and interferons. These cytokines exert their biological functions
      through Janus tyrosine kinases and signal transducer and activator of
      transcription factors. The cytokine-inducible Src homology 2 protein (CIS) and
      suppressors of cytokine signaling (SOCS) are a family of intracellular proteins,
      several of which have emerged as key physiological regulators of cytokine
      responses, including those that regulate the inflammatory systems. In this short
      review, we focused on the molecular mechanism of the action of CIS/SOCS family
      proteins and their roles in Toll-like receptor signal regulation and inflammatory
      diseases.

PMID- 14726495
TI  - The mast cell: an antenna of the microenvironment that directs the immune
      response.
AB  - Mast cells (MCs) have long been considered as critical effector cells during
      immunoglobulin (Ig)E-mediated allergic disease and immune response to parasites.
      Recent studies, however, suggest that this understanding of MC function is
      incomplete and does not consider the complex roles that MCs play in adaptive and
      innate immunity. The added function gives an innovative vision of regulation of
      immune responses and the development of autoimmune diseases. It had been assumed
      that the aggregation of Fc epsilon receptor I with IgE and specific antigen is
      the main stimulus able to induce the MC activation, degranulation, release, and
      generation of mediators of the allergic reaction. However, MCs exhibit an array
      of molecules involved in cell-cell and cell-extracellular matrix adhesion,
      mediating delivery of costimulatory signals that empower those cells with an
      ability to react to multiple nonspecific and specific stimuli. Their tissue
      distribution and their capability to release many cytokines after stimulation
      indicate MCs as potential regulatory linkers between innate and acquired
      immunity. In this review, we will summarize some findings on the roles of MCs in
      innate and acquired immunity, on the molecular mechanism and signaling pathways,
      and on selective signals that induce discrete MC response and its ability to
      polarize adaptive-immune response.

PMID- 14726496
TI  - Receptor tyrosine kinases and the regulation of macrophage activation.

PMID- 14726497
TI  - PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan
      by macrophages.
AB  - Pentraxin 3 (PTX3) is a tumor necrosis factor and interleukin-1beta-stimulated
      gene that encodes a long PTX with proinflammatory activity. Here, we show that
      peritoneal macrophages derived from PTX3 transgenic (Tg) mice express higher
      levels of PTX3 mRNA than macrophages from wild-type (WT) mice, at basal level as
      well as upon stimulation with zymosan (Zy). Macrophages from Tg mice also showed
      improved opsonin-independent phagocytosis of Zy particles and the yeast form of
      the fungus Paracoccidioides brasiliensis. In the case of P. brasiliensis, an
      enhanced microbicidal activity accompanied by higher production of nitric oxide
      was also observed in macrophages from Tg mice. Using fluorescein-activated cell
      sorter analysis and reverse transcriptase-polymerase chain reaction, we
      demonstrated that basal level of Toll-like receptor-6 and Zy-induced dectin-1
      expression was slightly but consistently higher in macrophages from Tg mice than
      in macrophages from WT mice. Recombinant (r)PTX3 protein binds to Zy particles as
      well as to yeast cells of P. brasiliensis and addition of rPTX3, to a culture of
      WT-derived macrophages containing Zy leads to an increase in the phagocytic
      index, which parallels that of Tg-derived macrophages, demonstrating the opsonin
      like activity of PTX3. It is important that blockade of dectin-1 receptor
      inhibited the phagocytosis of Zy particles by WT and PTX3 Tg macrophages,
      pointing out the relevant role of dectin-1 as the main receptor involved in Zy
      uptake. Our results provide evidence for a role of PTX3 as an important component
      of the innate-immune response and as part of the host mechanisms that control
      fungal recognition and phagocytosis.

PMID- 14726498
TI  - Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide
      gene.
AB  - Transgenic mice expressing an inducible suicide gene, which allows systemic and
      reversible elimination of macrophages, were developed. A macrophage-specific c
      fms promoter was used to express enhanced green fluorescent protein and a drug
      inducible suicide gene that leads to Fas-mediated apoptosis in resting and
      cycling cells of the macrophage lineage. Transgenic mice were fertile, of normal
      weight, and showed no abnormal phenotype before drug exposure. The transgene was
      expressed constitutively in macrophages and dendritic cells (DC) but not
      significantly in T cells or B cells. Induction of the suicide gene led to
      depletion of 70-95% of macrophages and DC in nearly all tissues examined.
      Depletion reduced the ability to clear bacteria from the blood and led to
      increased bacterial growth in the liver. Depleted mice displayed several
      abnormalities, including splenomegaly, lymphadenopathy, thymic atrophy,
      extramedullary hematopoiesis, and development of peritoneal adhesions. This new,
      transgenic line will be useful in investigating the role of macrophages and DC.

PMID- 14726499
TI  - Leukocyte fluid shear response in the presence of glucocorticoid.
AB  - Leukocytes respond to physiological fluid shear stress ( approximately 1.5
      dyn/cm(2)) by cytoplasmic reorganization. The cytoplasm is also influenced,
      however, by glucocorticoids. In this study, we explore how glucocorticoids may
      affect the leukocyte fluid shear response. Normal leukocytes, exposed to fluid
      shear in vitro during active migration, retract pseudopods accompanied by
      modestly decreasing intracellular calcium ions. In contrast, dexamethasone (DX)
      treated leukocytes project pseudopods after shear exposure with a significant
      rise in intracellular calcium ions, an effect that can be blocked by voltage
      dependent calcium channel blockers. Although a cyclic adenine monophosphate
      analog blocks calcium influx and pseudopod projection by DX, inhibition of A
      kinase induces reversal of the shear response, as seen with DX treatment. DX also
      reverses the leukocyte shear response in vivo in the rat circulation. Leukocytes
      that adhere to the endothelium in postcapillary venules of control rats return
      into the circulation only after pseudopod retraction, and in DX-treated rats,
      adherent leukocytes return into the circulation still with projecting pseudopods.
      The fraction of circulating leukocytes with pseudopods in DX-treated rats is
      higher than in controls. Thus, the reversal of leukocyte shear response by
      glucocorticoids may contribute to an enhanced incidence of circulating leukocytes
      with pseudopods, a process that affects the kinetics of these cells in the
      microcirculation.

PMID- 14726500
TI  - Controlling the Toll road to dendritic cell polarization.
AB  - The activation of dendritic cells (DC) via Toll-like receptors (TLRs) plays a
      decisive role in shaping the outcome of primary immune responses. Following TLR
      engagement by microbial products, DC migrate from peripheral tissues to lymphoid
      organs and up-regulate major histocompatibility complex and costimulatory
      molecules, acquiring the unique capacity to prime pathogen-specific, naive T
      cells. In addition, DC determine the character of the ensuing immune response by
      secreting cytokines that drive the development of T cells into T helper cell type
      1 (Th1), Th2, or T regulatory effector cells. Three major factors influence the
      pattern of cytokines released by DC and accordingly, the Th balance: the lineage
      to which DC belong; the maturation stimulus; and inflammatory mediators present
      at the site of infection. A major focus of this review is the capacity of DC to
      integrate these factors and elicit distinct classes of immune responses.

PMID- 14726501
TI  - Apoptosis of human primary B lymphocytes is inhibited by N-acetyl-L-cysteine.
AB  - Thiols are important molecules to control apoptosis. This study examined the
      effect of N-acetyl-L-cysteine (NAC) on in vitro spontaneous apoptosis of human
      tonsillar B lymphocytes (TBL). Results show that NAC inhibits TBL apoptosis and
      maintains their survival in vitro. The antiapoptotic action of NAC is
      progressively reduced when its addition to culture is delayed, is reversible, and
      is not blocked by cycloheximide. The antiapoptotic activity of NAC is associated
      with its ability to inhibit caspase-3 and -7 proteolytic processing, DNA
      fragmentation factor 45 cleavage, and DNA fragmentation. Furthermore, NAC
      inhibits BID cleavage and cytochrome c release from mitochondria and increases
      the expression of Bcl-2 and Bcl(XL) survival proteins. However, it has no effect
      on caspase-9 cleavage and increases that of caspase-8 and poly(adenosine 5'
      diphosphate-ribose)polymerase. We conclude that NAC-induced inhibition of TBL
      apoptosis is associated with inhibition of caspase-3 and -7 processing and is
      accompanied by changes in several regulatory components of the apoptotic process.
      These results pose the question of whether microenvironment thiols may in part
      contribute to in vivo B cell survival.

PMID- 14726502
TI  - TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying
      the human tumor necrosis factor alpha gene: a phase I study in patients with
      solid tumors.
AB  - PURPOSE: TNFerade is a replication deficient adenovector that expresses human
      tumor necrosis factor alpha under control of the radiation-inducible Egr-1
      promoter. The goals of this study were to determine the safety and toxicity of
      TNFerade in combination with radiation therapy. PATIENTS AND METHODS: TNFerade
      was administered by intratumoral administration, weekly for 6 weeks with
      concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 x 10(7)
      particle units [pu] to 4 x 10(11) pu) in patients with solid tumors being treated
      with radiation. RESULTS: Thirty-six patients were assessable for toxicity and 30
      for tumor response. Most frequent TNFerade-related toxicities were fever (22%),
      injection site pain (19%), and chills (19%). No dose-limiting toxicities were
      observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response
      (five complete responses, nine partial responses, and seven minimal responses).
      In four of five patients with synchronous lesions, a differential response
      between lesions treated with TNFerade + radiation compared with radiation only
      was observed. CONCLUSION: This is the first human study with TNFerade and
      radiation. The integrated treatment was well tolerated in patients with
      predominantly prior treatment-refractory solid tumors. Controlled prospective
      clinical trials have been initiated to more fully define the therapeutic
      contribution of TNFerade.

PMID- 14726503
TI  - Mortality after cure of testicular seminoma.
AB  - PURPOSE: To determine the incidence of potentially treatment-related mortality in
      long-term survivors of testicular seminoma treated by orchiectomy and radiation
      therapy (XRT). PATIENTS AND METHODS: From all 477 men with stage I or II
      testicular seminoma treated at The University of Texas M.D. Anderson Cancer
      Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999,
      453 never sustained relapse of their disease. Long-term survival for these 453
      men was evaluated with the person-years method to determine the standardized
      mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac
      deaths, and cancer deaths using standard US data for males. RESULTS: After a
      median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival
      rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the
      entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not
      excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77);
      but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac
      specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly
      elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91
      (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years
      of follow-up (P <.01). An increased mortality was evident in patients treated
      with and without mediastinal XRT. CONCLUSION: Long-term survivors of seminoma
      treated with post-orchiectomy XRT are at significant excess risk of death as a
      result of cardiac disease or second cancer. Management strategies that minimize
      these risks but maintain the excellent hitherto observed cure rates need to be
      actively pursued.

PMID- 14726504
TI  - CEBPA mutations in younger adults with acute myeloid leukemia and normal
      cytogenetics: prognostic relevance and analysis of cooperating mutations.
AB  - PURPOSE: To assess the prognostic relevance of mutations in the CEBPA gene
      encoding CCAAT/enhancer binding protein alpha (C/EBP alpha) in a large
      prospective series of younger adults with acute myeloid leukemia (AML) and normal
      cytogenetics. PATIENTS AND METHODS: The entire CEBPA coding region was sequenced
      in diagnostic samples from 236 AML patients 16 to 60 years of age with normal
      cytogenetics who were uniformly treated on two consecutive protocols of the AML
      Study Group Ulm, and CEBPA mutation status was correlated with clinical outcome.
      RESULTS: CEBPA mutations were detected in 36 (15%) of 236 patients. Twenty-one
      (9%) of 236 patients had mutations predicted to result in loss of C/EBP alpha
      function. Remission duration and overall survival (OS) were significantly longer
      for the 36 patients with CEBPA mutations (P =.01 and P =.05, respectively). On
      multivariate analysis, wild-type CEBPA was an independent prognostic marker
      affecting remission duration (hazard ratio, 2.85; P =.01) and OS (hazard ratio,
      1.87; P =.04). Analysis of cooperating mutations (both types of activating FLT3
      mutations and MLL partial tandem duplications) showed that FLT3 mutations had no
      significant prognostic influence in patients with CEBPA mutations. Furthermore,
      there was no significant overlap between the subgroup of patients with CEBPA
      mutation with predicted loss of C/EBP alpha function and patients with FLT3 or
      MLL mutations, suggesting that CEBPA loss-of-function mutations define a distinct
      biologic subclass of AML with normal cytogenetics. CONCLUSION: Mutant CEBPA
      predicts favorable prognosis and may improve risk stratification in AML patients
      with normal cytogenetics.

PMID- 14726505
TI  - Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a
      toxicity with therapeutic implications.
AB  - PURPOSE: Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is
      often used in melanoma patients, but phase III data show that it is no more
      effective than standard dacarbazine. Extended TMZ dosing regimens may be superior
      by delivering the drug continuously at a higher dose over time. Using an extended
      dosing schedule, we noted a high incidence of lymphopenia and occasional
      opportunistic infections (OIs). Here we report our retrospective experience in
      the first 97 patients. MATERIALS AND METHODS: TMZ was administered at 75
      mg/m(2)/d orally for 6 weeks every 8 weeks, although nine patients were treated
      continuously without a break. Seventeen patients were treated with TMZ alone; 73
      patients received TMZ with thalidomide; seven patients received TMZ with low-dose
      interferon alfa. RESULTS: Median duration of TMZ treatment was 113 days; 29%
      received > or = 24 weeks of therapy. Lymphopenia was seen in 60% of patients
      (absolute lymphocyte count < 800/microL) with a median of 101 days to
      lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia.
      Lymphopenia was not more common in patients treated concomitantly with
      thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced
      by TMZ affected the CD4(+) compartment preferentially. There were two documented
      OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections
      indicative of T-cell dysfunction in another 21 patients. CONCLUSION: TMZ at this
      dose and schedule results in CD4(+) lymphopenia in a majority of patients that
      can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for
      patients who develop sustained lymphopenia on TMZ.

PMID- 14726506
TI  - Temozolomide for melanoma: new toxicities and new opportunities.

PMID- 14726507
TI  - TNFerade to the rescue? Guidelines for evaluating phase I cancer gene transfer
      trials.

PMID- 14726508
TI  - Loss of C/EBP alpha and favorable prognosis of acute myeloid leukemias: a
      biological paradox.

PMID- 14726509
TI  - Radiotherapy in stage I seminoma of the testis.

PMID- 14726510
TI  - Ontogeny of proteolytic immunity: IgM serine proteases.
AB  - We report the chemical activity of immunoglobulin micro and kappa/lambda subunits
      expressed on the surface of B cells and in secreted IgM antibodies (Abs) found in
      the preimmune repertoire. Most of the nucleophilic reactivity of B cells measured
      by formation of covalent adducts of a hapten amidino phosphonate diester was
      attributed to micro and kappa/lambda subunits of the B cell receptor. Secreted
      IgM Abs displayed superior nucleophilic reactivity than IgG Abs. IgM Abs
      catalyzed the cleavage of model peptide substrates at rates up to 344-fold
      greater than IgG Abs. Catalytic activities were observed in polyclonal IgM Abs
      from immunologically naive mice and humans without immunological disease, as well
      as monoclonal IgM Abs to unrelated antigens. Comparison of several IgM Abs
      indicated divergent activity levels and substrate preferences, with the common
      requirement of a basic residue flanking the cleavage site. Fab fragments of a
      monoclonal IgM Ab expressed catalytic activity, confirming the V domain location
      of the catalytic site. The catalytic reaction was inhibited by the covalently
      reactive hapten probe and diisopropylfluorophosphate, suggesting a serine
      protease-like mechanism. These observations indicate the existence of serine
      protease-like BCRs and secreted IgM Abs as innate immunity components with
      potential roles in B cell development and Ab effector functions.

PMID- 14726511
TI  - Bloodstream form-specific up-regulation of silent vsg expression sites and
      procyclin in Trypanosoma brucei after inhibition of DNA synthesis or DNA damage.
AB  - The African trypanosome Trypanosoma brucei transcribes the active variant surface
      glycoprotein (VSG) gene from one of about 20 VSG expression sites (ESs). In order
      to study ES control, we made reporter lines with a green fluorescent protein gene
      inserted behind the promoter of different ESs. We attempted to disrupt the
      silencing machinery, and we used fluorescence-activated cell sorter analysis for
      the rapid and sensitive detection of ES up-regulation. We find that a range of
      treatments that either block nuclear DNA synthesis, like aphidicolin, or modify
      DNA-like cisplatin and 1-methyl-3-nitro-1-nitrosoguanidine results in up
      regulation of silent ESs. Aphidicolin treatment was the most effective, with
      almost 80% of the cells expressing green fluorescent protein from a silent ES.
      All of these treatments blocked the cells in S phase. In contrast, a range of
      toxic chemicals had little or no effect on expression. These included berenil and
      pentamidine, which selectively cleave the mitochondrial kinetoplast DNA, the
      metabolic inhibitors suramin and difluoromethylornithine, and the mitotic
      inhibitor rhizoxin. Up-regulation also affected other RNA polymerase I (pol I)
      transcription units, as procyclin genes were also up-regulated after cells were
      treated with either aphidicolin or DNA-modifying agents. Strikingly, this up
      regulation of silent pol I transcription units was bloodstream form-specific and
      was not observed in insect form T. brucei. We postulate that the redistribution
      of a limiting bloodstream form-specific factor involved in both silencing and DNA
      repair results in the derepression of normally silenced pol I transcription units
      after DNA damage.

PMID- 14726512
TI  - Organization and function of the small Tim complexes acting along the import
      pathway of metabolite carriers into mammalian mitochondria.
AB  - Tim9, Tim10a, and Tim10b are members of the family of small Tim proteins located
      in the intermembrane space of mammalian mitochondria. In yeast, members of this
      family act along the TIM22 import pathway during import of metabolite carriers
      and other integral inner membrane proteins. Here, we show that the human small
      proteins form two distinct hetero-oligomeric complexes. A 70-kDa complex that
      contains Tim9 and Tim10a and a Tim9-10a-10b that is part of a higher molecular
      weight assembly of 450 kDa. This distribution among two complexes suggests Tim10b
      to be the functional homologue of yeast Tim12. Both human complexes are tightly
      associated with the inner membrane and, compared with yeast, soluble 70-kDa
      complexes appear to be completely absent in the intermembrane space. Thus, the
      function of soluble 70-kDa complexes as trans-site receptors for incoming carrier
      proteins is not conserved from lower to higher eukaryotes. During import, the
      small Tim complexes directly interact with human adenine nucleotide translocator
      (ANT) in transit in a metal-dependent manner. For insertion of carrier
      preproteins into the inner membrane, the human small Tim proteins directly
      interact with human Tim22, the putative insertion pore of the TIM22 translocase.
      However, in contrast to yeast, only a small fraction of Tim9-Tim10a-Tim10b
      complex is in a stable association with Tim22. We conclude that different
      mechanisms and specific requirements for import and insertion of mammalian
      carrier preproteins have evolved in higher eukaryotes.

PMID- 14726513
TI  - Interfacial enzymology of parvovirus phospholipases A2.
AB  - The capsid of parvoviruses proteins were recently shown to contain secreted
      phospholipase A(2) (sPLA(2))-like activity that is required during host cell
      entry. Parvoviral PLA(2) domains have little sequence identity with sPLA(2)s and
      lack disulfide bonds. In the present study, after bacterial expression and
      purification, the biochemical characterizations of these first PLA(2)s identified
      in viruses have been investigated, and a comparison has been made with other
      known PLA(2)s. The specific activities of three viral PLA(2)s differed by 3
      orders of magnitude, with porcine parvovirus PLA(2) displaying a specific
      activity similar to that of the most active sPLA(2)s (e.g. human group IIA) and
      the human AAV2 and B19 parvoviral enzymes displaying approximately 10(3) lower
      specific activities (similar to human sPLA(2) groups IIE and XIIA). These
      differences were not caused by weaker Ca(2+) or interfacial binding. The specific
      activities of the viral PLA(2)s on zwitterionic or anionic phospholipid vesicles
      were comparable. The viral PLA(2)s did not display a preference for unsaturated
      versus saturated sn-2 fatty acyl chains and hydrolyzed all major classes of
      glycero-phospholipids except phosphatidylinositol. Incubation of mammalian cells
      with porcine parvovirus PLA(2) led to the release of arachidonic acid into the
      culture medium. Interestingly, among nine previously known sPLA(2) inhibitors,
      only a subset showed inhibition of the viral PLA(2)s and with weak potency,
      indicating that the active sites of these new enzymes are structurally distinct
      from those of sPLA(2)s. Based on these distinct enzymatic and structural
      properties, we propose to classify the parvovirus PLA(2)s within the PLA(2)
      superfamily as group XIII enzymes.

PMID- 14726514
TI  - AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors: AGS3
      blocks the sensitization of adenylyl cyclase following prolonged stimulation of a
      Galpha(i)-coupled receptor by influencing processing of Galpha(i).
AB  - AGS3-LONG and AGS3-SHORT contain G-protein regulatory motifs that interact with
      and stabilize the GDP-bound conformation of Galpha(i) > Galpha(o). AGS3 and
      related proteins may influence signal strength or duration as well as the
      adaptation of the signaling system associated with sustained stimulation. To
      address these issues, we determined the effect of AGS3 on the integration of
      stimulatory (Galpha(s)-mediated vasoactive intestinal peptide receptor) and
      inhibitory (Galpha(i)-mediated alpha(2)-adrenergic receptor (alpha(2)-AR))
      signals to adenylyl cyclase in Chinese hamster ovary cells. AGS3-SHORT and AGS3
      LONG did not alter the VIP-induced increase in cAMP or the inhibitory effect of
      alpha(2)-AR activation. System adaptation was addressed by determining the
      influence of AGS3 on the sensitization of adenylyl cyclase that occurs following
      prolonged activation of a Galpha(i)-coupled receptor. Incubation of cells with
      the alpha(2)-AR agonist UK14304 (1 microm) for 18 h resulted in a approximately
      1.8-fold increase in the vasoactive intestinal peptide-induced activation of
      adenylyl cyclase, and this was associated with a decrease in membrane-associated
      Galpha(i3). Both effects were blocked by AGS3-SHORT. AGS3-SHORT also decreased
      the rate of Galpha(i3) decay. A mutant AGS3-SHORT incapable of binding G-protein
      was inactive. These data suggest that AGS3 and perhaps other G-protein regulatory
      motif-containing proteins increase the stability of Galpha(i) in the membrane,
      which influences the adaptation of the cell to prolonged activation of Galpha(i)
      coupled receptors.

PMID- 14726515
TI  - Tandem orientation of duplicated xanthine dehydrogenase genes from Arabidopsis
      thaliana: differential gene expression and enzyme activities.
AB  - Xanthine dehydrogenase from the plant Arabidopsis thaliana was analyzed on
      molecular and biochemical levels. Whereas most other organisms appear to own only
      one gene for xanthine dehydrogenase A. thaliana possesses two genes in tandem
      orientation spaced by 704 base pairs. The cDNAs as well as the proteins AtXDH1
      and AtXDH2 share an overall identity of 93% and show high homologies to xanthine
      dehydrogenases from other organisms. Whereas AtXDH2 mRNA is expressed
      constitutively, alterations of AtXDH1 transcript levels were observed at various
      stresses like drought, salinity, cold, and natural senescence, but also after
      abscisic acid treatment. Transcript alteration did not mandatorily result in
      changes of xanthine dehydrogenase activities. Whereas salt treatment had no
      effect on xanthine dehydrogenase activities, cold stress caused a decrease, but
      desiccation and senescence caused a strong increase of activities in leaves.
      Because AtXDH1 presumably is the more important isoenzyme in A. thaliana it was
      expressed in Pichia pastoris, purified, and used for biochemical studies. AtXDH1
      protein is a homodimer of about 300 kDa consisting of identical subunits of 150
      kDa. Like xanthine dehydrogenases from other organisms AtXDH1 uses hypoxanthine
      and xanthine as main substrates and is strongly inhibited by allopurinol. AtXDH1
      could be activated by the purified molybdenum cofactor sulfurase ABA3 that
      converts inactive desulfo-into active sulfoenzymes. Finally it was found that
      AtXDH1 is a strict dehydrogenase and not an oxidase, but is able to produce
      superoxide radicals indicating that besides purine catabolism it might also be
      involved in response to various stresses that require reactive oxygen species.

PMID- 14726516
TI  - The Arabidopsis copper transporter COPT1 functions in root elongation and pollen
      development.
AB  - Copper plays a dual role in aerobic organisms, as both an essential and a
      potentially toxic element. To ensure copper availability while avoiding its toxic
      effects, organisms have developed complex homeostatic networks to control copper
      uptake, distribution, and utilization. In eukaryotes, including yeasts and
      mammals, high affinity copper uptake is mediated by the Ctr family of copper
      transporters. This work is the first report on the physiological function of
      copper transport in Arabidopsis thaliana. We have studied the expression pattern
      of COPT1 in transgenic plants expressing a reporter gene under the control of the
      COPT1 promoter. The reporter gene is highly expressed in embryos, trichomes,
      stomata, pollen, and root tips. The involvement of COPT1 in copper acquisition
      was investigated in CaMV35S::COPT1 antisense transgenic plants. Consistent with a
      decrease in COPT1 expression and the associated copper deprivation, these plants
      exhibit increased mRNA levels of genes that are down-regulated by copper,
      decreased rates of (64)Cu uptake by seedlings and reduced steady state levels of
      copper as measured by atomic absorption spectroscopy in mature leaves.
      Interestingly, COPT1 antisense plants also display dramatically increased root
      length, which is completely and specifically reversed by copper addition, and an
      increased sensitivity to growth inhibition by the copper-specific chelator
      bathocuproine disulfonic acid. Furthermore, COPT1 antisense plants exhibit pollen
      development defects that are specifically reversed by copper. Taken together,
      these studies reveal striking plant growth and development roles for copper
      acquisition by high affinity copper transporters.

PMID- 14726517
TI  - Sp2 DNA binding activity and trans-activation are negatively regulated in
      mammalian cells.
AB  - Previous studies have indicated that Sp2 binds poorly to GC-rich sequences bound
      by Sp1 and Sp3, and further functional analyses of Sp2 have been limited. To
      study Sp2-mediated transcription, we employed a PCR-based protocol to determine
      the Sp2 consensus DNA-binding sequence (5'-GGGCGGGAC-3') and performed kinetic
      experiments to show that Sp2 binds this consensus sequence with high affinity
      (225 pm) in vitro. To determine the functional consequence of Sp2 interaction
      with this sequence in vivo, we transformed well characterized Sp-binding sites
      within the dihydrofolate reductase (DHFR) promoter to consensus Sp2-binding
      sites. Incorporation of Sp2-binding sites within the DHFR promoter increased Sp2
      mediated trans-activation in transient co-transfection experiments but also
      revealed Sp2 to be a relatively weak trans-activator with little or no capacity
      for additive or synergistic trans-activation. Using chimeric molecules prepared
      with portions of Sp1 and Sp2 and the human prostate-specific antigen promoter, we
      show that Sp2 DNA binding activity and trans-activation are negatively regulated
      in mammalian cells. Taken together, our data indicate that Sp2 is functionally
      distinct relative to other Sp family members and suggest that Sp2 may play a
      unique role in cell physiology.

PMID- 14726518
TI  - Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated
      pacemaker channels: molecular coupling between the S4-S5 and C-linkers.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels have a
      transmembrane topology that is highly similar to voltage-gated K(+) channels, yet
      HCN channels open in response to membrane hyperpolarization instead of
      depolarization. The structural basis for the "inverted" voltage dependence of HCN
      gating and how voltage sensing by the S1-S4 domains is coupled to the opening of
      the intracellular gate formed by the S6 domain are unknown. Coupling could arise
      from interaction between specific residues or entire transmembrane domains. We
      previously reported that the mutation of specific residues in the S4-S5 linker of
      HCN2 (i.e. Tyr-331 and Arg-339) prevented normal channel closure presumably by
      disruption of a crucial interaction with the activation gate. Here we
      hypothesized that the C-linker, a carboxyl terminus segment that connects S6 to
      the cyclic nucleotide binding domain, interacts with specific residues of the S4
      S5 linker to mediate coupling. The recently solved structure of the C-linker of
      HCN2 indicates that an alpha-helix (the A'-helix) is located near the end of each
      S6 domain, the presumed location of the activation gate. Ala-scanning mutagenesis
      of the end of S6 and the A'-helix identified five residues that were important
      for normal gating as mutations disrupted channel closure. However, partial
      deletion of the C-linker indicated that the presence of only two of these
      residues was required for normal coupling. Further mutation analyses suggested
      that a specific electrostatic interaction between Arg-339 of the S4-S5 linker and
      Asp-443 of the C-linker stabilizes the closed state and thus participates in the
      coupling of voltage sensing and activation gating in HCN channels.

PMID- 14726519
TI  - High density lipoprotein uptake by scavenger receptor SR-BII.
AB  - Scavenger receptor class B, type I (SR-BI) mediates selective uptake of high
      density lipoprotein (HDL) lipids. It is unclear whether this process occurs at
      the cell membrane or via endocytosis. Our group previously identified an
      alternative mRNA splicing variant of SR-BI, named SR-BII, with an entirely
      different, yet highly conserved cytoplasmic C terminus. In this study we aimed to
      compare HDL uptake by both isoforms. Whereas SR-BI was mainly ( approximately
      70%) localized on the surface of transfected Chinese hamster ovary cells, as
      determined by biotinylation, HDL binding at 4 degrees C, and studies of enhanced
      green fluorescent protein-tagged SR-BI/II fusion proteins, the majority of SR-BII
      ( approximately 80-90%) was expressed intracellularly. The cellular distribution
      of SR-BI was not affected by deletion of the C terminus, which suggests that the
      distinct C terminus of SR-BII is responsible for its intracellular expression.
      Pulse-chase experiments showed that SR-BII rapidly internalized HDL protein,
      whereas in the case of SR-BI most HDL protein remained surface bound. Like its
      ligand, SR-BII was more rapidly endocytosed compared with SR-BI. Despite more
      rapid HDL uptake by SR-BII than SR-BI, selective cholesteryl ether uptake was
      significantly lower. Relative to their levels of expression at the cell surface,
      however, both isoforms mediated selective uptake with similar efficiency. HDL
      protein that was internalized by SR-BII largely co-localized with transferrin in
      the endosomal recycling compartment. Within the endosomal recycling compartment
      of SR-BII cells, there was extensive co-localization of internalized HDL lipid
      and protein. These results do not support a model that selective lipid uptake by
      SR-BI requires receptor/ligand recycling within the cell. We conclude that SR-BII
      may influence cellular cholesterol trafficking and homeostasis in a manner that
      is distinct from SR-BI.

PMID- 14726520
TI  - Crystal structures of QacR-diamidine complexes reveal additional multidrug
      binding modes and a novel mechanism of drug charge neutralization.
AB  - The Staphylococcus aureus multidrug-binding protein QacR represses transcription
      of the plasmid-encoded membrane protein QacA, a multidrug efflux transporter.
      QacR is induced by multiple structurally dissimilar monovalent and bivalent
      cationic lipophilic compounds, many of which are effluxed from the cell by QacA
      via the proton motive force. The multidrug-binding pocket of QacR has been shown
      to be quite extensive and features several glutamates and multiple aromatic
      residues. To date, the structure of only one QacR-bivalent cationic drug complex
      (that of QacR bound to dequalinium) has been determined, and how other longer or
      shorter bivalent cationic compounds bind is unknown. Here we report the crystal
      structures of QacR bound to two cytotoxic bivalent diamidines, pentamidine and
      hexamidine. These compounds are structurally similar, differing by only one
      methylene carbon in the alkyl chain linker. However, this small difference
      results in very dissimilar binding modes. Similar to dequalinium, hexamidine
      spans the multidrug-binding pocket, and its positively charged benzamidine groups
      are neutralized by residues Glu-57 and Glu-120. Pentamidine binds QacR in a novel
      fashion whereby one of its benzamidine groups interacts with residue Glu-63, and
      the other is neutralized by carbonyl and side chain oxygen atoms. Thus, these
      structures demonstrate that a formal negative charge is not a prerequisite for
      binding positively charged drugs and underscore the versatility of the QacR and,
      likely, all multidrug-binding pockets.

PMID- 14726521
TI  - Androgens negatively regulate forkhead transcription factor FKHR (FOXO1) through
      a proteolytic mechanism in prostate cancer cells.
AB  - The ability of androgens to inhibit apoptosis in both normal and malignant
      prostatic cells has been well documented. However, the underlying mechanisms are
      understood poorly. Here we demonstrated that forkhead transcription factor FKHR
      (FOXO1)-induced death of LNCaP cells was blocked by a synthetic androgen R1881.
      Androgen treatment also resulted in a reduction in transcriptional activity of
      FKHR in these cells. Moreover, treatment of LNCaP cells with R1881 led to a
      decrease in the intact FKHR protein (70 kDa) and an increase in a faster
      migrating protein band (60 kDa). Androgen-enhanced appearance of the 60-kDa
      protein was diminished specifically by lysosomal acidic cysteine protease
      inhibitors. Mass spectrometry analyses of the purified FLAG-tagged 70- and 60-kDa
      proteins demonstrated that the 60-kDa species is a FKHR protein product that
      lacks about 120 amino acid residues of the C-terminal end. Mutagenesis of the
      basic amino acid Arg(537) in the protease cleavage region, as suggested by mass
      spectrometry, abrogated both the androgen-induced accumulation of the 60-kDa
      product and decrease in cell death induced by FKHR, suggesting that the residue
      Arg(537) is a potential protease cleavage site. Finally, ectopic expression of
      the first 537 amino acids of FKHR produced an inhibitory effect on
      transcriptional activity of the intact protein. Together, these results suggest
      that androgens induce increased activity of an acidic cysteine protease, which in
      turn cleaves FKHR. This provides a mechanism by which androgens protect prostate
      cancer cells from the killing effect of FKHR.

PMID- 14726522
TI  - Distinct isoprenoid origins of cis- and trans-zeatin biosyntheses in Arabidopsis.
AB  - Plants produce the common isoprenoid precursors isopentenyl diphosphate and
      dimethylallyl diphosphate (DMAPP) through the methylerythritol phosphate (MEP)
      pathway in plastids and the mevalonate (MVA) pathway in the cytosol. To assess
      which pathways contribute DMAPP for cytokinin biosynthesis, metabolites from each
      isoprenoid pathway were selectively labeled with (13)C in Arabidopsis seedlings.
      Efficient (13)C labeling was achieved by blocking the endogenous pathway
      genetically or chemically during the feed of a (13)C labeled precursor specific
      to the MEP or MVA pathways. Liquid chromatography-mass spectrometry analysis
      demonstrated that the prenyl group of trans-zeatin (tZ) and isopentenyladenine is
      mainly produced through the MEP pathway. In comparison, a large fraction of the
      prenyl group of cis-zeatin (cZ) derivatives was provided by the MVA pathway. When
      expressed as fusion proteins with green fluorescent protein in Arabidopsis cells,
      four adenosine phosphate-isopentenyltransferases (AtIPT1, AtIPT3, AtIPT5, and
      AtIPT8) were found in plastids, in agreement with the idea that the MEP pathway
      primarily provides DMAPP to tZ and isopentenyladenine. On the other hand, AtIPT2,
      a tRNA isopentenyltransferase, was detected in the cytosol. Because the
      prenylated adenine moiety of tRNA is usually of the cZ type, the formation of cZ
      in Arabidopsis seedlings might involve the transfer of DMAPP from the MVA pathway
      to tRNA. Distinct origins of large proportions of DMAPP for tZ and cZ
      biosynthesis suggest that plants are able to separately modulate the level of
      these cytokinin species.

PMID- 14726523
TI  - Protons activate the delta-subunit of the epithelial Na+ channel in humans.
AB  - The amiloride-sensitive epithelial Na(+) channel (ENaC) controls Na(+) transport
      into cells and across epithelia. So far, four homologous subunits of mammalian
      ENaC have been isolated and are denoted as alpha, beta, gamma, and delta.
      ENaCdelta can associate with beta and gamma subunits and generate a constitutive
      current that is 2 orders of magnitude larger than that of homomeric ENaCdelta.
      However, the distribution pattern of ENaCdelta is not consistent with that of the
      beta and gamma subunits. ENaCdelta is expressed mainly in the brain in contrast
      to beta and gamma subunits, which are expressed in non-neuronal tissues. To
      explain this discrepancy, we searched for novel functional properties of
      homomeric ENaCdelta and investigated the detailed tissue distribution in humans.
      When human ENaCdelta was expressed in Xenopus oocytes and Chinese hamster ovary
      cells, a reduction of extracellular pH activated this channel (half-maximal pH
      for an activation of 5.0), and the acid-induced current was abolished by
      amiloride. The most striking finding was that the desensitization of the acid
      evoked current was much slower (by approximately 10% 120 s later), dissociating
      from the kinetics of acid-sensing ion channels in the degenerin/epithelial Na(+)
      channel family, which were rapidly desensitized during acidification. RNA dot
      blot analyses showed that ENaCdelta mRNA was widely distributed throughout the
      brain and was also expressed in the heart, kidney, and pancreas in humans.
      Northern blotting confirmed that ENaCdelta was expressed in the cerebellum and
      the hippocampus. In conclusion, human ENaCdelta activity is regulated by protons,
      indicating that it may contribute to the pH sensation and/or pH regulation in the
      human brain.

PMID- 14726524
TI  - Trypsin IV, a novel agonist of protease-activated receptors 2 and 4.
AB  - Certain serine proteases signal to cells by cleaving protease-activated receptors
      (PARs) and thereby regulate hemostasis, inflammation, pain and healing. However,
      in many tissues the proteases that activate PARs are unknown. Although pancreatic
      trypsin may be a physiological agonist of PAR(2) and PAR(4) in the small
      intestine and pancreas, these receptors are expressed by cells not normally
      exposed pancreatic trypsin. We investigated whether extrapancreatic forms of
      trypsin are PAR agonists. Epithelial cells lines from prostate, colon, and airway
      and human colonic mucosa expressed mRNA encoding PAR(2), trypsinogen IV, and
      enteropeptidase, which activates the zymogen. Immunoreactive trypsinogen IV was
      detected in vesicles in these cells. Trypsinogen IV was cloned from PC-3 cells
      and expressed in CHO cells, where it was also localized to cytoplasmic vesicles.
      We expressed trypsinogen IV with an N-terminal Igkappa signal peptide to direct
      constitutive secretion and allow enzymatic characterization. Treatment of
      conditioned medium with enteropeptidase reduced the apparent molecular mass of
      trypsinogen IV from 36 to 30 kDa and generated enzymatic activity, consistent
      with formation of trypsin IV. In contrast to pancreatic trypsin, trypsin IV was
      completely resistant to inhibition by polypeptide inhibitors. Exposure of cell
      lines expressing PAR(2) and PAR(4) to trypsin IV increased [Ca(2+)](i) and
      strongly desensitized cells to PAR agonists, whereas there were no responses in
      cells lacking these receptors. Thus, trypsin IV is a potential agonist of PAR(2)
      and PAR(4) in epithelial tissues where its resistance to endogenous trypsin
      inhibitors may permit prolonged signaling.

PMID- 14726525
TI  - Induction of G1 arrest and apoptosis in human jurkat T cells by
      pentagalloylglucose through inhibiting proteasome activity and elevating p27Kip1,
      p21Cip1/WAF1, and Bax proteins.
AB  - Pentagalloylglucose, which is found in many medicinal plants, can arrest the cell
      cycle at G(1) phase through down-regulation of cyclin-dependent kinases 2 and 4
      and up-regulation of the cyclin-dependent kinase inhibitors p27(Kip1) and
      p21(Cip1/WAF1) in human breast cancer cells. Pentagalloylglucose also induces
      apoptosis in human leukemic cells. However, the mechanisms by which
      pentagalloylglucose induces these effects is unclear. We now show that
      pentagalloylglucose inhibits the activities of purified 20 and 26 S proteasomes
      in vitro, the 26 S proteasome in Jurkat T cell lysates, and chymotrypsin-like
      activity of the 26 S proteasome in intact Jurkat T cells. The turnover of
      p27(Kip1) and p21(Cip1/WAF1), which is necessary for cell cycle progression
      mediated by proteasome degradation, was disrupted by treatment of human Jurkat T
      cells with pentagalloylglucose. This was shown by cycloheximide treatment and in
      vivo pulse-chase labeling experiments, and this effect correlated with the arrest
      of proliferation of Jurkat T cells at G(1). Inhibition of the proteasome by
      pentagalloylglucose and by the proteasome inhibitor MG132 caused accumulation of
      ubiquitin-tagged proteins in Jurkat T cells. The addition of pentagalloylglucose
      to Jurkat T cells enhanced the stability of the proteasome substrate Bax and
      increased cytochrome c release and apoptosis. Our findings suggest a mechanism
      for the effect of pentagalloylglucose on the cell cycle in human leukemic cells:
      that pentagalloylglucose down-regulates proteasome-mediated pathways because it
      is a proteasome inhibitor.

PMID- 14726526
TI  - Engineering a three-cysteine, one-histidine ligand environment into a new
      hyperthermophilic archaeal Rieske-type [2Fe-2S] ferredoxin from Sulfolobus
      solfataricus.
AB  - We heterologously overproduced a hyperthermostable archaeal low potential (E(m) =
      -62 mV) Rieske-type ferredoxin (ARF) from Sulfolobus solfataricus strain P-1 and
      its variants in Escherichia coli to examine the influence of ligand substitutions
      on the properties of the [2Fe-2S] cluster. While two cysteine ligand residues
      (Cys(42) and Cys(61)) are essential for the cluster assembly and/or stability,
      the contributions of the two histidine ligands to the cluster assembly in the
      archaeal Rieske-type ferredoxin appear to be inequivalent as indicated by much
      higher stability of the His(64) --> Cys variant (H64C) than the His(44) --> Cys
      variant (H44C). The x-ray absorption and resonance Raman spectra of the H64C
      variant firmly established the formation of a novel, oxidized [2Fe-2S] cluster
      with one histidine and three cysteine ligands in the archaeal Rieske-type protein
      moiety. Comparative resonance Raman features of the wild-type, natural abundance
      and uniformly (15)N-labeled ARF and its H64C variant showed significant mixing of
      the Fe-S and Fe-N stretching characters for an oxidized biological [2Fe-2S]
      cluster with partial histidine ligation.

PMID- 14726527
TI  - In vivo studies of translational repression mediated by the granulocyte
      macrophage colony-stimulating factor AU-rich element.
AB  - The AU-rich element (ARE) controls the turnover of many unstable mRNAs and their
      translation. The granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE is
      known to be a destabilizing element, but its role in translation remains unclear.
      Here we studied in vivo the role of the GM-CSF ARE on the mRNA and protein
      expressions of an enhanced green fluorescent protein reporter gene. The GM-CSF
      ARE had a repressor effect on translation independently of its effect on mRNA
      levels. In the context of an internal ribosome entry site, the GM-CSF ARE still
      repressed translation but was no longer functional as a destabilizing element.
      Gel retardation assays showed that poly(A)-binding protein is displaced from the
      poly(A) tail when the ARE is present in the 3'-untranslated region. These data
      suggest that the GM-CSF ARE controls translation and mRNA decay by interfering
      with poly(A)-binding protein-mediated mRNA circularization.

PMID- 14726528
TI  - Identification of residues that determine the absence of a Ca(2+)/myristoyl
      switch in neuronal calcium sensor-1.
AB  - The neuronal calcium sensor (NCS) family of Ca(2+)-binding proteins regulates a
      number of different processes in neurons and photoreceptor cells. The first of
      these proteins to be characterized, recoverin, was shown to exhibit a
      Ca(2+)/myristoyl switch whereby its N-terminal myristoyl group is sequestered in
      the Ca(2+)-free form and is exposed on Ca(2+) binding to allow the protein to
      become membrane-associated. It has subsequently been shown that certain other
      family members also exhibit this mechanism in living cells. In contrast, NCS-1
      does not show the Ca(2+)/myristoyl switch and is membrane-associated even at low
      Ca(2+) concentrations. We have used sequence comparison combined with information
      from structural analyses to attempt to identify candidate residues within the NCS
      proteins that determine whether or not the Ca(2+)/myristoyl switch operates in
      cells and have tested their functional significance by mutagenesis. The results
      show that NCS-1 possesses residues within its N terminus that lock the myristoyl
      group in an exposed conformation. In addition, other structural aspects within
      the C-terminal domains are required to allow the switch to operate. We have
      determined a key role for residues within the motif EELTRK in NCS-1 in keeping
      the myristoyl group exposed and allowing the protein to be constitutively
      membrane-associated.

PMID- 14726529
TI  - PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor
      1alpha from pVHL-independent degradation.
AB  - Hypoxia inducible factor 1 (HIF-1), a heterodimeric transcription factor composed
      of HIF-1alpha and HIF-1beta subunits, serves as a key regulator of metabolic
      adaptation to hypoxia. The amount of HIF-1alpha protein is regulated either by
      attenuating von Hippel-Lindau protein (pVHL)-dependent ubiquitination and
      subsequent 26 S proteasomal degradation or by enhancing cap-dependent mRNA
      translation, presumably involving a phosphatidyinositol 3-kinase (PI3K)/Akt
      regulated pathway. In addition, it became apparent that Hsp90 protects HIF-1alpha
      from oxygen-independent degradation. Here we present evidence that PI3K/Akt is
      required for heat shock proteins to stabilize HIF-1alpha. In pVHL-deficient renal
      cell carcinoma cells, PI3K inhibition by LY294002 and wortmannin or transfection
      of either a dominant negative PI3K or a kinase-dead Akt mutant substantially
      lowered constitutively expressed HIF-1alpha without altering HIF-1alpha mRNA.
      Inhibitors of mitogen-activated protein kinase kinase (MAPKK) such as PD98059 or
      the p38 MAPK inhibitor SB203580 showed no interference. Considering that PI3K
      inhibitors down-regulated heat shock protein 90 (Hsp90) as well as Hsp70
      expression and moreover attenuated heat- or hypoxia-induced Hsp70 as well as
      hypoxia-induced Hsp90 up-regulation we conclude that PI3K inhibition promoted
      degradation of HIF-1alpha indirectly by reducing steady state concentrations of
      Hsp90 and/or Hsp70. HIF-1alpha co-immunoprecipitated with Hsp90/Hsp70 and direct
      binding of Hsp70 to the oxygen-dependent degradation domain (ODD) of HIF-1alpha
      was proven by a pull-down assay and a peptide array. PI3K-mediated degradation of
      HIF-1alpha was confirmed in HEK 293 cells under hypoxia, suggesting that heat
      shock proteins constitute an integral component for HIF-1alpha accumulation. We
      conclude that PI3K/Akt contributes to HIF-1alpha stabilization by provoking
      expression of heat shock proteins.

PMID- 14726530
TI  - Real-time analysis of ternary complex on particles: direct evidence for partial
      agonism at the agonist-receptor-G protein complex assembly step of signal
      transduction.
AB  - We developed a novel and generalized approach to investigate G protein-coupled
      receptor molecular assemblies. We solubilized a fusion protein consisting of the
      beta(2)-adrenergic receptor and green fluorescent protein (GFP) for bead-based
      flow cytometric analysis. beta(2)-Adrenergic receptor GFP bound to
      dihydroalprenolol-conjugated beads, providing a K(d) for the fusion protein and,
      in competition with beta(2)-adrenergic receptor ligands, K(d) values for agonists
      and antagonists. Beads displaying chelated nickel bound purified hexahistidine
      tagged G protein heterotrimers and, subsequently, the binary complex of agonist
      with beta(2)-adrenergic receptor GFP. The dose-response curves of ternary complex
      formation revealed maximal assembly for ligands previously classified as full
      agonists and reduced assembly for ligands previously classified as partial
      agonists. Guanosine 5'-3-O-(thio)triphosphate-induced dissociation rates of the
      ternary complex were the same for full and partial agonists. Soluble G protein,
      competing with ternary complexes on beads provided an affinity estimate of
      agonist-receptor complexes to G protein. When performed simultaneously, the two
      assemblies discriminated between agonist, antagonist or inactive molecule in a
      manner appropriate for high throughput, small volume drug discovery. The
      assemblies can be further generalized to other G protein coupled receptor protein
      protein interactions.

PMID- 14726531
TI  - Translational regulation of terminal oligopyrimidine mRNAs induced by serum and
      amino acids involves distinct signaling events.
AB  - Various mitogenic or growth inhibitory stimuli induce a rapid change in the
      association of terminal oligopyrimidine (TOP) mRNAs with polysomes. It is
      generally believed that such translational control hinges on the mammalian target
      of rapamycin (mTOR)-S6 kinase pathway. Amino acid availability affects the
      translation of TOP mRNAs, although the signaling pathway involved in this
      regulation is less well characterized. To investigate both serum- and amino acid
      dependent control of TOP mRNA translation and the signaling pathways involved,
      HeLa cells were subjected to serum and/or amino acid deprivation and stimulation.
      Our results indicate the following. 1). Serum and amino acid deprivation had
      additive effects on TOP mRNA translation. 2). The serum content of the medium
      specifically affected TOP mRNA translation, whereas amino acid availability
      affected both TOP and non-TOP mRNAs. 3). Serum signaling to TOP mRNAs involved
      only a rapamycin-sensitive pathway, whereas amino acid signaling depended on both
      rapamycin-sensitive and rapamycin-insensitive but wortmannin-sensitive events.
      4). Eukaryotic initiation factor-2alpha phosphorylation increased during amino
      acid deprivation, but not following serum deprivation. Interestingly, rapamycin
      treatment suggests a novel connection between the mTOR pathway and eukaryotic
      initiation factor-2alpha phosphorylation in mammalian cells, which may not,
      however, be involved in TOP mRNA translational regulation.

PMID- 14726532
TI  - An extensive requirement for transcription factor IID-specific TAF-1 in
      Caenorhabditis elegans embryonic transcription.
AB  - The general transcription factor TFIID sets the mRNA start site and consists of
      TATA-binding protein and associated factors (TAF(II)s), some of which are also
      present in SPT-ADA-GCN5 (SAGA)-related complexes. In yeast, results of multiple
      studies indicate that TFIID-specific TAF(II)s are not required for the
      transcription of most genes, implying that intact TFIID may have a surprisingly
      specialized role in transcription. Relatively little is known about how TAF(II)s
      contribute to metazoan transcription in vivo, especially at developmental and
      tissue-specific genes. Previously, we investigated functions of four shared
      TFIID/SAGA TAF(II)s in Caenorhabditis elegans. Whereas TAF-4 was required for
      essentially all embryonic transcription, TAF-5, TAF-9, and TAF-10 were
      dispensable at multiple developmental and other metazoan-specific promoters. Here
      we show evidence that in C. elegans embryos transcription of most genes requires
      TFIID-specific TAF-1. TAF-1 is not as universally required as TAF-4, but it is
      essential for a greater proportion of transcription than TAF-5, -9, or -10 and is
      important for transcription of many developmental and other metazoan-specific
      genes. TAF-2, which binds core promoters with TAF-1, appears to be required for a
      similarly substantial proportion of transcription. C. elegans TAF-1 overlaps
      functionally with the coactivator p300/CBP (CBP-1), and at some genes it is
      required along with the TBP-like protein TLF(TRF2). We conclude that during C.
      elegans embryogenesis TAF-1 and TFIID have broad roles in transcription and
      development and that TFIID and TLF may act together at certain promoters. Our
      findings imply that in metazoans TFIID may be of widespread importance for
      transcription and for expression of tissue-specific genes.

PMID- 14726533
TI  - Observation of an intact noncovalent homotrimer of detergent-solubilized rat
      microsomal glutathione transferase-1 by electrospray mass spectrometry.
AB  - Microsomal glutathione transferase-1 (MGST1) is a membrane-bound enzyme involved
      in the detoxification of xenobiotics and the protection of cells against
      oxidative stress. The proposed active form of the enzyme is a noncovalently
      associated homotrimer that binds one substrate glutathione molecule/trimer. In
      this study, this complex has been directly observed by electrospray mass
      spectrometry analysis of active rat liver MGST1 reconstituted in a minimum amount
      of detergent. The measured mass of the homotrimer is 53 kDa, allowing for the
      mass of three MGST molecules in complex with one glutathione molecule. Collision
      induced dissociation of the trimer complex resulted in the formation of monomer
      and homodimer ion species. Two distinct species of homodimer were observed, one
      unliganded and one identified as a homodimer.glutathione complex. Activation of
      the enzyme by N-ethylmaleimide through modification of Cys(49) (Svensson, R.,
      Rinaldi, R., Swedmark, S., and Morgenstern, R. (2000) Biochemistry 39, 15144
      15149) was monitored by the observation of an appropriate increase in mass in
      both the denatured monomeric and native trimeric forms of MGST1. Together, the
      data correspond well with the proposed functional organization of MGST1. These
      results also represent the first example of direct electrospray mass spectrometry
      analysis of a detergent-solubilized multimeric membrane protein complex in its
      native state.

PMID- 14726534
TI  - Quorum sensing in Staphylococci is regulated via phosphorylation of three
      conserved histidine residues.
AB  - Staphylococcus aureus cause infections by producing toxins, a process regulated
      by cell-cell communication (quorum sensing) through the histidine-phosphorylation
      of the target of RNAIII-activating protein (TRAP). We show here that TRAP is
      highly conserved in staphylococci and contains three completely conserved
      histidine residues (His-66, His-79, His-154) that are phosphorylated and
      essential for its activity. This was tested by constructing a TRAP(-) strain with
      each of the conserved histidine residues changed to alanine by site-directed
      mutagenesis. All mutants were tested for pathogenesis in vitro (expression of
      RNAIII and hemolytic activity) and in vivo (murine cellulitis model). Results
      show that RNAIII is not expressed in the TRAP(-) strain, that it is non
      hemolytic, and that it does not cause disease in vivo. These pathogenic
      phenotypes could be rescued in the strain containing the recovered traP,
      confirming the importance of TRAP in S. aureus pathogenesis. The phosphorylation
      of TRAP mutated in any of the conserved histidine residues was significantly
      reduced, and mutants defective in any one of these residues were non-pathogenic
      in vitro or in vivo, whereas those mutated in a non-conserved histidine residue
      (His-124) were as pathogenic as the wild type. These results confirm the
      importance of the three conserved histidine residues in TRAP activity. The
      phosphorylation pattern, structure, and gene organization of TRAP deviates from
      signaling molecules known to date, suggesting that TRAP belongs to a novel class
      of signal transducers.

PMID- 14726535
TI  - In vivo substrate specificity of periplasmic disulfide oxidoreductases.
AB  - In Escherichia coli, a family of periplasmic disulfide oxidoreductases catalyzes
      correct disulfide bond formation in periplasmic and secreted proteins. Despite
      the importance of native disulfide bonds in the folding and function of many
      proteins, a systematic investigation of the in vivo substrates of E. coli
      periplasmic disulfide oxidoreductases, including the well characterized oxidase
      DsbA, has not yet been performed. We combined a modified osmotic shock
      periplasmic extract and two-dimensional gel electrophoresis to identify
      substrates of the periplasmic oxidoreductases DsbA, DsbC, and DsbG. We found 10
      cysteine-containing periplasmic proteins that are substrates of the disulfide
      oxidase DsbA, including PhoA and FlgI, previously established DsbA substrates.
      This technique did not detect any in vivo substrates of DsbG, but did identify
      two substrates of DsbC, RNase I and MepA. We confirmed that RNase I is a
      substrate of DsbC both in vivo and in vitro. This is the first time that DsbC has
      been shown to affect the in vivo function of a native E. coli protein, and the
      results strongly suggest that DsbC acts as a disulfide isomerase in vivo. We also
      demonstrate that DsbC, but not DsbG, is critical for the in vivo activity of
      RNase I, indicating that DsbC and DsbG do not function identically in vivo. The
      absence of substrates for DsbG suggests either that the in vivo substrate
      specificity of DsbG is more limited than that of DsbC or that DsbG is not active
      under the growth conditions tested. Our work represents one of the first times
      the in vivo substrate specificity of a folding catalyst system has been
      systematically investigated. Because our methodology is based on the simple
      assumption that the absence of a folding catalyst should cause its substrates to
      be present at decreased steady-state levels, this technique should be useful in
      analyzing the substrate specificity of any folding catalyst or chaperone for
      which mutations are available.

PMID- 14726536
TI  - RhoA/ROCK signaling suppresses hypertrophic chondrocyte differentiation.
AB  - Coordinated proliferation and differentiation of growth plate chondrocytes is
      required for normal growth and development of the endochondral skeleton, but
      little is known about the intracellular signal transduction pathways regulating
      these processes. We have investigated the roles of the GTPase RhoA and its
      effector kinases ROCK1/2 in hypertrophic chondrocyte differentiation. RhoA,
      ROCK1, and ROCK2 are expressed throughout chondrogenic differentiation. RhoA
      overexpression in chondrogenic ATDC5 cells results in increased proliferation and
      a marked delay of hypertrophic differentiation, as shown by decreased induction
      of alkaline phosphatase activity, mineralization, and expression of the
      hypertrophic markers collagen X, bone sialoprotein, and matrix metalloproteinase
      13. These effects are accompanied by activation of cyclin D1 transcription and
      repression of the collagen X promoter by RhoA. In contrast, inhibition of
      Rho/ROCK signaling by the pharmacological inhibitor Y27632 inhibits chondrocyte
      proliferation and accelerates hypertrophic differentiation. Dominant-negative
      RhoA also inhibits induction of the cyclin D1 promoter by parathyroid hormone
      related peptide. Finally, Y27632 treatment partially rescues the effects of RhoA
      overexpression. In summary, we identify the RhoA/ROCK signaling pathway as a
      novel and important regulator of chondrocyte proliferation and differentiation.

PMID- 14726537
TI  - The Haemophilus influenzae Hia autotransporter contains an unusually short
      trimeric translocator domain.
AB  - Gram-negative bacterial autotransporter proteins are a growing group of virulence
      factors that are characterized by their ability to cross the outer membrane
      without the help of accessory proteins. A conserved C-terminal beta-domain is
      critical for targeting of autotransporters to the outer membrane and for
      translocation of the N-terminal "passenger" domain to the bacterial surface. We
      have demonstrated previously that the Haemophilus influenzae Hia adhesin belongs
      to the autotransporter family, with translocator activity residing in the C
      terminal 319 residues. To gain further insight into the mechanism of
      autotransporter protein translocation, we performed a structure-function analysis
      on Hia. In initial experiments, we generated a series of in-frame deletions and a
      set of chimeric proteins containing varying regions of the Hia C terminus fused
      to a heterologous passenger domain and discovered that the final 76 residues of
      Hia are both necessary and sufficient for translocation. Analysis by flow
      cytometry revealed that the region N-terminal to this shortened translocator
      domain is surface localized, further suggesting that this region is not involved
      in beta-barrel formation or in translocation of the passenger domain. Western
      analysis demonstrated that the translocation-competent regions of the C terminus
      migrated at masses consistent with trimers, suggesting that the Hia C terminus
      oligomerizes. Furthermore, fusion proteins containing a heterologous passenger
      domain demonstrated that similarly small C-terminal regions of Yersinia sp. YadA
      and Neisseria meningitidis NhhA are translocation-competent. These data provide
      experimental support for a unique subclass of autotransporters characterized by a
      short trimeric translocator domain.

PMID- 14726539
TI  - NMR analysis shows that a b-type variant of Hydrogenobacter thermophilus
      cytochrome c552 retains its native structure.
AB  - Conversion of Hydrogenobacter thermophilus cytochrome c(552) into a b-type
      cytochrome by mutagenesis of both heme-binding cysteines to alanines
      significantly reduces the stability of the protein (Tomlinson, E. J., and
      Ferguson, S. J. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 5156-5160). To
      understand the effects of this change on the structure and dynamics of the
      protein, hetero-nuclear (15)N-edited NMR techniques have been used to
      characterize this b-type variant. The backbone (15)N, (1)H(N), and (1)H(alpha),
      and (1)H(beta) resonances of the protein have been assigned. Analysis of
      (3)J(HN)alpha coupling constants, nuclear Overhauser enhancement intensities, and
      chemical shift index data demonstrates that the four alpha-helices present in the
      wild-type protein are retained in the b-type variant. Comparison of the chemical
      shifts for the b-type and wild-type proteins indicates that the tertiary
      structures of the two proteins are closely similar. Some subtle differences are,
      however, observed for residues in the N-terminal region and in the vicinity of
      the heme-binding pocket. Hydrogen exchange studies show that there are 25
      backbone amide protons that exchange very slowly in the b-type variant and
      confirm that the fluctuations within the b-type protein are of a similar extent
      to those in the wild-type protein. These data demonstrate the notable retention
      of the native secondary structure and tertiary fold despite the absence of
      covalent linkages between the heme group and the protein.

PMID- 14726538
TI  - Intestinal tumor progression is associated with altered function of KLF5.
AB  - Kruppel-like transcription factors have been linked to cell growth regulation and
      tumorigenesis in a number of systems. In the intestinal epithelium, expression of
      KLF5 (IKLF/BTEB2) is limited to proliferating crypt cells, indicating a growth
      promoting role. Consistent with this role, we demonstrate that expression of KLF5
      in non-transformed intestinal epithelial cells (ileal IEC-18 and Immorto-Min
      Colon Epithelial (IMCE) cells) enhances colony formation, cyclin D1
      transcription, and cell growth. However, in contrast to these effects in non
      transformed cells, KLF5 reduced colony number, failed to enhance cyclin D1
      transcription, and was negatively correlated with cell growth in colon cancer
      cell lines. The relationship between tumor progression and KLF5 was further
      investigated using Ras-mediated transformation of IEC-18 and IMCE cells as
      syngeneic models. Ras-transformation recapitulated differences in the effects of
      KLF5 on cell growth and cyclin D1 transcription, providing a direct link between
      intestinal tumor progression and altered function of KLF5. Ras-transformation
      also markedly down-regulated KLF5; further analysis indicated that reduced
      expression of KLF5 mRNA and destabilization of KLF5 protein occur in intestinal
      tumors. Reduced levels of KLF5 mRNA were also detected in APC(min) mouse and
      human familial adenomatous polyposis adenomas compared with normal crypt
      epithelium, indicating that down-regulation of KLF5 is an early event in
      intestinal tumorigenesis in vivo. Collectively, these data indicate that
      intestinal tumor progression is associated with a change in the growth-related
      functions of KLF5 and that intestinal tumors down-regulate KLF5 expression by
      multiple mechanisms.

PMID- 14726540
TI  - Both thrombotic and nonthrombotic cardiovascular and cerebrovascular side effects
      of nonsteroidal anti-inflammatory drugs should be considered.

PMID- 14726541
TI  - Association between high serum ferritin levels and carotid atherosclerosis in the
      study of health in Pomerania (SHIP).
AB  - BACKGROUND AND PURPOSE: Several studies have provided evidence for a relationship
      between body iron load and cardiovascular disease. We analyzed the association of
      serum ferritin levels with carotid atherosclerosis. METHODS: We assessed intima
      media thickness and plaque prevalence in the carotid arteries by high-resolution
      ultrasound among 2443 participants (1200 women; age, 45 to 79 years) in the Study
      of Health in Pomerania (SHIP), a population-based study in northeast Germany.
      RESULTS: In multivariate analysis, serum ferritin levels were not independently
      associated with carotid intima-media thickness among women or men. In contrast,
      the relationship between serum ferritin levels and carotid plaque prevalence was
      significant among men (odds ratio per 1-SD increase of serum ferritin levels,
      1.33; 95% confidence interval, 1.08 to 1.44) yet not among women (odds ratio,
      1.29; 95% confidence interval, 0.98 to 1.75). However, both men and women showed
      a dose-response relation between serum ferritin levels and carotid
      atherosclerosis in which higher serum ferritin levels were associated with
      greater odds ratios for carotid plaque prevalence. Additionally, there was an
      interaction of serum ferritin levels with low-density lipoprotein (LDL)
      cholesterol (P=0.039) among men in which the association of serum ferritin levels
      with carotid plaque prevalence became stronger with increasing LDL cholesterol
      levels. CONCLUSIONS: Our study identified a relationship between serum ferritin
      levels and carotid atherosclerosis that was potentiated by LDL cholesterol. This
      relationship adds support to the hypothesis of a link between iron and
      cardiovascular disease.

PMID- 14726542
TI  - Prospective evaluation of the alcohol dehydrogenase gamma1/gamma2 gene
      polymorphism and risk of stroke.
AB  - BACKGROUND AND PURPOSE: Genetic polymorphism of the alcohol dehydrogenase type 3
      gene (ADH1C) has recently been associated with reduced risk of myocardial
      infarction. However, data on risk of stroke are not available. METHODS: We
      examined the possible association between the ADH1C gamma1/gamma2 polymorphism
      and risk of stroke in a prospective, nested case-control sample from the
      Physicians' Health Study of 14 916 apparently healthy men who were followed over
      a 12-year period. A total of 320 incident stroke cases and 550 age- and smoking
      matched controls were genotyped. RESULTS: All observed genotype frequencies were
      in Hardy-Weinberg equilibrium. The allele and genotype distributions of the
      polymorphism tested were similar between cases and controls, such that the
      relative risk of stroke was 1.04 for ADH1C gamma1/gamma2 (95% CI=0.85 to 1.28;
      P=0.65) assuming an additive mode of inheritance. Contrary to prior findings for
      myocardial infarction, no evidence of association was observed to suggest an
      effect modification of ADH1C genotypes with the level of alcohol consumption on
      the risk of stroke. Similar findings were observed in subgroup analysis
      restricted to ischemic events. CONCLUSIONS: In this large, prospective study, we
      found little evidence that the ADH1C gamma1/gamma2 polymorphism is associated
      with risk of future stroke. These data raise the possibility of important
      pathologic differences in ischemia between the coronary and cerebral
      circulations.

PMID- 14726543
TI  - Ischemic stunning of the brain: early recanalization without immediate clinical
      improvement in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Early arterial recanalization (ER) with intravenous
      tissue plasminogen activator (tPA) can lead to dramatic clinical recovery,
      whereas some patients do not experience immediate clinical improvement. METHODS:
      Consecutive patients received tPA 0.9 mg/kg IV within 3 hours after symptom
      onset. All had M1 or M2 middle cerebral artery occlusions on pretreatment
      transcranial Doppler. Patients were continuously monitored for 2 hours after
      bolus. ER was defined as the Thrombolysis in Brain Ischemia intracranial flow
      increase by >or=1 grade. Stroke severity (National Institutes of Health Stroke
      Scale [NIHSS]) and recovery (modified Rankin Scale) were assessed independently
      of transcranial Doppler. RESULTS: One hundred twenty patients (mean age, 68+/-15
      years; 63 women; median NIHSS, 17; range, 5 to 29; 90% with >or=10 points)
      received tPA at a median of 120 minutes, 50% within the first 2 hours. ER was
      observed in 73 patients (32 complete, 41 partial). No immediate clinical changes
      (n=23) or worsening (by 1 to 6 points on NIHSS, n=4) was observed in 37% of ERs
      (nonresponders). Complete ER was found in 8 of these 27 patients. At 24 hours, 22
      of 27 patients (82%) had persisting deficits of NIHSS >or=10 points, yet 37% of
      these nonresponders (10 of 27) still achieved good outcome (modified Rankin
      score, 0 to 2) at 3 months. Among nonresponders with good outcome, 100% had
      detectable residual flow signals, and 70% had compensatory flow diversion on
      prebolus transcranial Doppler compared with 65% and 29% of nonresponders with
      poor outcome (P<0.05). Compared with responders (n=46), nonresponders had similar
      prebolus median NIHSS of 16 to 17 points, bolus times of 120 to 132 minutes,
      median speed of thrombolysis (30 minutes), and ER times of 190 to 193 minutes
      after onset. Reocclusion occurred in 3 of 4 patients with clinical worsening, 30%
      of other nonresponders, and 22% of responders. Symptomatic hemorrhage rate was 4%
      in both groups. At 3 months, mortality was 33% in nonresponders compared with 9%
      in responders (P=0.001). CONCLUSIONS: After successful arterial ER with tPA
      therapy, lack of early clinical changes or worsening is relatively common (37%)
      and appears to be independent of time to tPA bolus or reperfusion. However, with
      tPA alone, at least one third of these nonresponders still achieved good outcomes
      at 3 months, suggesting the possibility of a "stunned brain" syndrome with
      delayed recovery. Several different mechanisms may potentially account for this
      phenomenon.

PMID- 14726544
TI  - Coactivation of GABA(A) and GABA(B) receptor results in neuroprotection during in
      vitro ischemia.
AB  - BACKGROUND AND PURPOSE: The possible neuroprotective effect of endogenous gamma
      aminobutyric acid (GABA) on the irreversible electrophysiological changes induced
      by in vitro ischemia on striatal neurons was investigated. In particular, the aim
      of the study was the characterization of the neuroprotective action of 2
      antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA
      transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA
      transaminase. METHODS: Extracellular field potential recordings were obtained
      from rat corticostriatal slice preparations. In vitro ischemia was delivered by
      switching to an artificial cerebrospinal fluid solution in which glucose was
      omitted and oxygen was replaced with N(2). RESULTS: An irreversible loss of the
      field potentials recorded from striatal neurons was observed after 10 minutes of
      ischemia in control solution. Conversely, tiagabine and vigabatrin partially
      prevented the ischemia-induced field potential loss. Surprisingly, both GABA(A)
      and GABA(B) receptor antagonists blocked these effects. Accordingly,
      neuroprotection could be obtained only when GABA(A) and GABA(B) receptor agonists
      were coapplied, but not when a single agonist was given in isolation.
      CONCLUSIONS: Antiepileptic drugs targeting GABAergic transmission can exert
      neuroprotective effects against ischemia by increasing endogenous GABA levels and
      via the activation of both GABA(A) and GABA(B) receptors.

PMID- 14726545
TI  - Synergistic effect of apolipoprotein E polymorphisms and cigarette smoking on
      risk of ischemic stroke in young adults.
AB  - BACKGROUND AND PURPOSE: The effect of apolipoprotein E (APOE) polymorphisms on
      stroke risk may be influenced by the coexistence of modifiable predisposing
      conditions. We explored the interactions of APOE genotypes and conventional risk
      factors in a case-control study of young adults with cerebral infarct. METHODS:
      We analyzed 124 consecutive patients (age, 34.7+/-7.3 years) and 147 age- and sex
      matched controls. APOE genotypes were determined by restriction fragment-length
      polymorphism analysis. RESULTS: The prevalence of the epsilon4 allele and
      epsilon34 genotype was slightly higher in cases than in controls (0.125 versus
      0.071 and 0.242 versus 0.136, respectively). Carriers of the epsilon34 genotype
      and epsilon4 allele were associated with an increased risk of stroke on
      multivariate analysis compared with the epsilon33 genotype and non-epsilon4
      carriers, respectively (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.10
      to 4.76; and OR, 2.27; 95% CI, 1.13 to 4.56). ORs for stroke were 2.99 (95% CI,
      1.64 to 5.45), 2.69 (95% CI, 1.25 to 5.77), and 5.39 (95% CI, 1.59 to 18.30) for
      smokers with the epsilon33 genotype, nonsmokers with the epsilon34 genotype, and
      smokers with the epsilon34 genotype, respectively, compared with nonsmokers with
      the epsilon33 genotype. Similar results were obtained when epsilon4 carriers and
      non-epsilon4 carriers were compared in the same interaction model. No significant
      interaction between APOE and hypertension was found. CONCLUSIONS: In young
      adults, the APOE epsilon4 allele and cigarette smoking act synergistically,
      increasing an individual's propensity to have a cerebral ischemic event. This
      finding may help in determining an individual's predisposition to stroke and more
      targeted preventive interventions.

PMID- 14726546
TI  - Long-term outcome of acute spinal cord ischemia syndrome.
AB  - BACKGROUND AND PURPOSE: Current knowledge of long-term outcome in patients with
      acute spinal cord ischemia syndrome (ASCIS) is based on few studies with small
      sample sizes and <2 years' follow-up. Therefore, we analyzed clinical features
      and outcome of all types of ASCIS to define predictors of recovery. METHODS: From
      January 1990 through October 2002, 57 patients with ASCIS were admitted to our
      center. Follow-up data were available for 54. Neurological syndrome and initial
      degree of impairment were defined according to American Spinal Injury Association
      (ASIA)/International Medical Society of Paraplegia criteria. Functional outcome
      was assessed by walking ability and bladder control. RESULTS: Mean age was 59.4
      years; 29 were women; and mean follow-up was 4.5 years. The origin was
      atherosclerosis in 33.3%, aortic pathology in 15.8%, degenerative spine disease
      in 15.8%, cardiac embolism in 3.5%, systemic hypotension in 1.8%, epidural
      anesthesia in 1.8%, and cryptogenic in 28%. The initial motor deficit was severe
      in 30% (ASIA grades A and B), moderate in 28% (ASIA C), and mild in 42% (ASIA D).
      At follow-up, 41% had regained full walking ability, 30% were able to walk with
      aids, 20% were wheelchair bound, and 9% had died. Severe initial impairment (ASIA
      A and B) and female sex were independent predictors of unfavorable outcome
      (P=0.012 and P=0.043). CONCLUSIONS: Considering a broad spectrum of clinical
      presentations and origins, the outcome in our study was more favorable than in
      previous studies reporting on ASCIS subgroups with more severe initial deficits.

PMID- 14726547
TI  - Wall shear stress is associated with intima-media thickness and carotid
      atherosclerosis in subjects at low coronary heart disease risk.
AB  - BACKGROUND AND PURPOSE: Systemic and local coronary heart disease (CHD) risk
      factors participate in atherogenesis. The role of wall shear stress, a major
      local risk factor, remains to be elucidated. METHODS: Two hundred thirty-four
      subjects were carefully characterized for the presence of hypertension,
      hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking and were
      divided into low- and high-risk groups. They underwent echo-Doppler examination
      of the carotid arteries. Atherosclerotic plaques and stenoses were detected,
      intima-media thickness (IMT) was measured, and wall shear stress was calculated.
      RESULTS: One hundred eight subjects were classified as low-risk individuals. The
      prevalence of carotid atherosclerosis in this group was 18.5%. Wall shear stress
      was 24.23+/-7.21 dyne/cm(2) in individuals without atherosclerosis and 16.89+/
      5.48 in those with atherosclerosis (P<0.000). In multiple regression analyses,
      wall shear stress, body mass index, and HDL cholesterol were inversely associated
      and total cholesterol was directly associated with the presence of
      atherosclerosis; only wall shear stress was associated with IMT. In the high-risk
      group the prevalence of atherosclerosis was 45.2%. Wall shear stress was 20.44+/
      6.82 dyne/cm(2) in subjects without atherosclerosis and 17.84+/-6.88 dyne/cm(2)
      in those with atherosclerosis (P=0.037). Age was the only variable associated
      with both carotid atherosclerosis and IMT. CONCLUSIONS: In subjects traditionally
      considered at low CHD risk, intima-media thickening and carotid atherosclerosis
      are significantly associated with low wall shear stress. In contrast, in subjects
      at high CHD risk, the contribution of wall shear stress seems to be masked, and
      age becomes the only factor significantly associated with both carotid
      atherosclerosis and IMT.

PMID- 14726548
TI  - Mild neurological symptoms despite middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: Only a small percentage of stroke patients are treated
      with thrombolytic therapy. We sought to determine whether vessel occlusion in
      mild strokes represented a new target population for interventional therapy.
      METHODS: We imaged 106 acute stroke patients with MRI. Patients were identified
      with evidence of middle cerebral artery (MCA) occlusion and mild or no stroke
      signs (National Institutes of Health Stroke Scale [NIHSS] <or=3). They were
      compared with patients with signs of stroke, NIHSS >3, and MCA occlusion.
      RESULTS: We identified 5 patients with absent flow on MRA in the MCA and mild or
      no stroke signs (NIHSS <or=3). All 5 were functionally independent at 3 months.
      CONCLUSIONS: Caution should be exercised in considering thrombolytic therapy in
      these patients. Quantification of perfusion imaging is required to identify "at
      risk" mild stroke populations.

PMID- 14726549
TI  - Agreement between patient and proxy assessments of health-related quality of life
      after stroke using the EQ-5D and Health Utilities Index.
AB  - BACKGROUND AND PURPOSE: Proxy informants can provide information on patients who
      are limited in ability to self-assess health-related quality of life (HRQL) after
      stroke. One alternative is to exclude assessments of such patients and attenuate
      generalizability. The purpose of this study was to examine patient-proxy
      agreement on the domains and summary scores of the EQ-5D and Health Utilities
      Index Mark 3 (HUI3) after stroke. METHODS: An observational longitudinal cohort
      of 124 patients hospitalized after ischemic stroke and their family caregivers
      completed the HRQL measures at baseline and were followed up for 6 months.
      Patient and proxy agreement was assessed by use of weighted kappa or the
      intraclass correlation coefficient (ICC). RESULTS: At baseline, the more
      observable domains of HRQL demonstrated greater agreement than the more
      subjective components. Cross-sectional point estimates of agreement were
      generally acceptable (ICC >0.70) for the EQ-5D Index and HUI3 summary scores when
      assessed >or=1 month after baseline. Agreement between change scores was
      generally poor to fair (ICC <0.60), but systematic bias was not observed for the
      indirect preference-based summary scores between baseline and 6 months.
      CONCLUSIONS: Results suggest that proxy assessments obtained 6 months after
      stroke are more reliable than those obtained within 2 to 3 weeks after stroke.
      Although proxy-assessed change scores for indirect preference-based summary
      scores of the EQ-5D and HUI3 provided suboptimal agreement with patient
      assessment, limited systematic bias may support their consideration as
      alternatives to missing data or statistical imputation. Further research into the
      validity and reliability of proxy assessments is suggested.

PMID- 14726550
TI  - Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidant-induced
      neuronal death.
AB  - BACKGROUND AND PURPOSE: Studies using animal models of stroke have shown that
      human serum albumin (HSA) significantly ameliorates cerebral ischemic injury
      after both transient and permanent ischemia, even when administered after the
      onset of ischemia or reperfusion. The mechanism of this effect remains uncertain,
      and prior studies suggest both indirect hemodynamic and direct cytoprotective
      effects. HSA is a potent antioxidant, in part because of its strong copper
      binding capacity. Here we examined the effect of HSA on oxidant-induced neuronal
      death in a cortical cell culture system. METHODS: Murine cortical cultures were
      exposed to oxidative stress generated by hydrogen peroxide and by a mixture of
      copper plus ascorbic acid. We examined the ability of HSA and a tetrapeptide
      occupying its N-terminus (DAHK) to prevent neuronal death after these challenges.
      RESULTS: H(2)O(2) and CuCl(2)/ascorbic acid were used at concentrations that, in
      the absence of HSA, killed >90% of the neurons. HSA provided complete protection
      at a concentration of 37.5 micromol/L and 50% protection at 3.75 micromol/L. The
      copper-binding tetrapeptide DAHK had nearly identical potency and efficacy. HSA
      and DAHK were also equally effective in preventing neuronal death induced by
      CuCl(2)/ascorbic acid. CONCLUSIONS: HSA has potent antioxidant properties,
      probably due to binding of copper and other transition metals. HSA extravasation
      into ischemic brain may provide neuroprotection by limiting metal-catalyzed
      oxidant stress. The tetrapeptide DAHK may be an effective, small-molecular-weight
      alternative to HSA as a therapeutic agent for stroke.

PMID- 14726551
TI  - Mild postischemic hypothermia prolongs the time window for gene therapy by
      inhibiting cytochrome C release.
AB  - BACKGROUND AND PURPOSE: We showed previously that Bcl-2 overexpression with the
      use of herpes simplex viral (HSV) vectors improved striatal neuron survival when
      delivered 1.5 hours after stroke but not when delivered 5 hours after stroke
      onset. Here we determine whether hypothermia prolongs the therapeutic window for
      gene therapy. METHODS: Rats were subjected to focal ischemia for 1 hour.
      Hypothermia (33 degrees C) was induced 2 hours after insult and maintained for 3
      hours. Five hours after ischemia onset, HSV vectors expressing Bcl-2 plus beta
      gal or beta-gal alone were injected into each striatum. Rats were killed 2 days
      later. RESULTS: Striatal neuron survival of Bcl-2-treated, hypothermic animals
      was improved 2- to 3-fold over control-treated, hypothermic animals and Bcl-2
      treated, normothermic animals. Neuron survival among normothermic, Bcl-2-treated
      animals was not different from control normothermics or control hypothermics.
      Double immunostaining of cytochrome c and beta-gal demonstrated that Bcl-2 plus
      hypothermia significantly reduced cytochrome c release. CONCLUSIONS: Postischemic
      mild hypothermia extended the time window for gene therapy neuroprotection using
      Bcl-2 and reduced cytochrome c release.

PMID- 14726552
TI  - Editorial comment--persisting dilemma: to treat or not to treat blood pressure in
      acute ischemic stroke.

PMID- 14726553
TI  - Blood pressure decrease during the acute phase of ischemic stroke is associated
      with brain injury and poor stroke outcome.
AB  - BACKGROUND AND PURPOSE: Studies on the relation between blood pressure (BP) and
      stroke outcome have shown contradictory results. We explored the association of
      systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological
      deterioration, infarct volume, neurological outcome, and mortality at 3 months.
      METHODS: We included 304 patients with acute ischemic stroke. SBP and DBP on
      admission and on the first day were the average values of all readings obtained
      in the emergency department and during a 24-hour period after patient allocation
      in the stroke unit. RESULTS: A U-shaped effect was observed: for every 10 mm Hg
      <or=180 mm Hg of SBP, the risk of early neurological deterioration, poor outcome,
      and mortality increased by 6%, 25%, and 7%, respectively, whereas for every 10 mm
      Hg >180 mm Hg, the risk of early neurological deterioration increased by 40% and
      the risk of poor outcome increased by 23%, with no effect on mortality. Mean
      infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg <or=180 and >180 mm
      Hg. A similar pattern was found in patients with DBP <or=100 or >100 mm Hg. These
      effects disappeared after adjustment for the use of antihypertensive drugs and BP
      drop >20 mm Hg within the first day, with the latter being the more important
      prognostic factor of poor outcome. CONCLUSIONS: High and low SBP and DBP, as well
      as a relevant drop in BP, are associated with poor prognosis in patients with
      ischemic stroke.

PMID- 14726554
TI  - Thalamic lesions in vascular dementia: low sensitivity of fluid-attenuated
      inversion recovery (FLAIR) imaging.
AB  - BACKGROUND AND PURPOSE: The criteria of the National Institute of Neurological
      Disorders and Stroke (NINDS)-Association Internationale pour la Recherche et
      l'Enseignement en Neurosciences (AIREN) include thalamic lesions for the
      diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain
      aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2
      weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity
      of these sequences to depict thalamic lesions. METHODS: We performed a blinded
      review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part
      of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This
      sample was drawn from a large multicenter trial on VaD and was expected to have a
      high prevalence of thalamic lesions. In a side-by-side review, including T1
      weighted images as well, lesions were classified according to presumed underlying
      pathology. RESULTS: The total number of thalamic lesions was 214. Two hundred
      eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR
      (chi(2)=5.1; P<0.05). Although the mean size of lesions detected on T2-WI and not
      on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected
      on both sequences (6.7 mm) (P<0.001), 5 of the 29 lesions >10 mm on T2-WI were
      not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic
      lesions and 30 (60%) of the 50 probable microbleeds. CONCLUSIONS: FLAIR should
      not be used as the only T2-weighted sequence to detect thalamic lesions in
      patients suspected of having VaD.

PMID- 14726555
TI  - Educational level and stroke mortality: a comparison of 10 European populations
      during the 1990s.
AB  - BACKGROUND AND PURPOSE: Variations between countries in occupational differences
      in stroke mortality were observed among men during the 1980s. This study
      estimates the magnitude of differences in stroke mortality by educational level
      among men and women aged >or=30 years in 10 European populations during the
      1990s. METHODS: Longitudinal data from mortality registries were obtained for 10
      European populations, namely Finland, Norway, Denmark, England/Wales, Belgium,
      Switzerland, Austria, Turin (Italy), Barcelona (Spain), and Madrid (Spain). Rate
      ratios (RRs) were calculated to assess the association between educational level
      and stroke mortality. The life table method was used to estimate the impact of
      stroke mortality on educational differences in life expectancy. RESULTS:
      Differences in stroke mortality according to educational level were of a similar
      magnitude in most populations. However, larger educational differences were
      observed in Austria. Overall, educational differences in stroke mortality were of
      similar size among men (RR, 1.27; 95% CI, 1.24 to 1.30) and women (RR, 1.29; 95%
      CI, 1.27 to 1.32). Educational differences in stroke mortality persisted at all
      ages in all populations, although they generally decreased with age. Eliminating
      these differences would on average reduce educational differences in life
      expectancy by 7% among men and 14% among women. CONCLUSIONS: Educational
      differences in stroke mortality were observed across Europe during the 1990s.
      Risk factors such as hypertension and smoking may explain part of these
      differences in several countries. Other factors, such as socioeconomic
      differences in healthcare utilization and childhood socioeconomic conditions, may
      have contributed to educational differences in stroke mortality across Europe.

PMID- 14726556
TI  - Framingham stroke risk profile and lowered cognitive performance.
AB  - BACKGROUND AND PURPOSE: The primary objective of this work was to describe the
      relationships between 10-year risk for stroke and multiple measures of cognitive
      performance for a large community-based sample of individuals who were free of
      clinical stroke and dementia at the time of risk assessment. METHODS:
      Participants were 1011 men and 1164 women from the Framingham Offspring Study.
      The Framingham Stroke Risk Profile was used to assess 10-year risk of stroke.
      Using a cross-sectional design, we assessed 10-year risk of stroke, the predictor
      variable, and cognitive performance, the outcome variable, at examination 7 of
      the Framingham Offspring Study. Multivariable linear regression models were used
      to relate 10-year risk of stroke to cognitive tests measuring multiple domains of
      cognitive functioning. RESULTS: With statistical adjustment for age, education,
      sex, and other correlates of both stroke and cognitive ability, an inverse
      association between increments in 10-year risk of stroke and cognitive
      performance level was observed for tests indexing visual-spatial memory,
      attention, organization, scanning, and abstract reasoning. CONCLUSIONS: In stroke
      and dementia-free individuals, higher 10-year risk for stroke is associated with
      performance decrements in multiple cognitive domains.

PMID- 14726557
TI  - Taxonomy: impediment or expedient?

PMID- 14726559
TI  - Vision for NASA. President Bush reaches for the moon.

PMID- 14726558
TI  - Infectious diseases. Viral DNA match spurs China's civet roundup.

PMID- 14726561
TI  - Math and science education. 2005 Bush budget pulls NSF schools funding.

PMID- 14726560
TI  - California. Stem cell research could be ballot issue.

PMID- 14726562
TI  - Ocean science. Panel to prepare plan for underwater network.

PMID- 14726563
TI  - India. Book triggers attack on research institute.

PMID- 14726564
TI  - Earth science. Panel urges shakeup of NOAA research.

PMID- 14726565
TI  - Epidemiology. Ebola outbreaks may have had independent sources.

PMID- 14726566
TI  - Australia. Hall found guilty of lesser misconduct.

PMID- 14726567
TI  - Large facilities. NSF told to open process for picking new projects.

PMID- 14726568
TI  - Physics. CESR launches last campaign.

PMID- 14726569
TI  - Careers. Joining a trend, scientists increasingly say 'call my agent'.

PMID- 14726571
TI  - American Geophysical Union meeting. An ill-mannered San Andreas?

PMID- 14726570
TI  - American Geophysical Union meeting. An early start for greenhouse warming?

PMID- 14726572
TI  - American Geophysical Union meeting. Vicissitudes of ancient climate.

PMID- 14726573
TI  - Crisis for biodiversity collections.

PMID- 14726574
TI  - Synchrotron-Cerenkov radiation.

PMID- 14726575
TI  - Open access to science and culture.

PMID- 14726576
TI  - Public health. A sound rationale needed for phase III HIV-1 vaccine trials.

PMID- 14726577
TI  - Neuroscience. Action, illusion, and perception.

PMID- 14726578
TI  - Psychology. Is language the key to human intelligence?

PMID- 14726579
TI  - Structural biology. Surprising news from the PCC.

PMID- 14726580
TI  - Astronomy. Unraveling brown dwarf origins.

PMID- 14726581
TI  - Astronomy. Brown dwarfs--faint at heart, rich in chemistry.

PMID- 14726582
TI  - Molecular biology. Breaking the silence.

PMID- 14726583
TI  - Unifying the epidemiological and evolutionary dynamics of pathogens.
AB  - A key priority for infectious disease research is to clarify how pathogen genetic
      variation, modulated by host immunity, transmission bottlenecks, and epidemic
      dynamics, determines the wide variety of pathogen phylogenies observed at scales
      that range from individual host to population. We call the melding of
      immunodynamics, epidemiology, and evolutionary biology required to achieve this
      synthesis pathogen "phylodynamics." We introduce a phylodynamic framework for the
      dissection of dynamic forces that determine the diversity of epidemiological and
      phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of
      this model is the Evolutionary Infectivity Profile, which captures the
      relationship between immune selection and pathogen transmission.

PMID- 14726584
TI  - Gene therapy insertional mutagenesis insights.

PMID- 14726585
TI  - Self-assembly of mesoscopic metal-polymer amphiphiles.
AB  - The assembly properties of two- and three-component rod-like building blocks
      consisting of gold and polymer block domains have been investigated. These
      structures behave like mesoscopic amphiphiles and form a series of single-layer
      superstructures consisting of bundles, tubes, and sheets depending upon the
      compositional periodicity. Unlike molecular systems, the template used to
      initially synthesize them plays a critical role in the assembly process by
      prealigning them in a manner that facilitates their assembly by optimizing the
      correct collisional orientation upon dissolution of the template. Tubular
      structures with tailorable diameters can be assembled in a predictable manner on
      the basis of an estimate of the hybrid rod packing parameters.

PMID- 14726586
TI  - Inferences on flow at the base of Earth's mantle based on seismic anisotropy.
AB  - We applied global waveform tomography to model radial anisotropy in the whole
      mantle. We found that in the last few hundred kilometers near the core-mantle
      boundary, horizontally polarized S-wave velocities (VSH) are, on average, faster
      (by approximately 1%) than vertically polarized S-wave velocities (VSV),
      suggesting a large-scale predominance of horizontal shear. This confirms that the
      D" region at the base of the mantle is also a mechanical boundary layer for
      mantle convection. A notable exception to this average signature can be found at
      the base of the two broad low-velocity regions under the Pacific Ocean and under
      Africa, often referred to as "superplumes," where the anisotropic pattern
      indicates the onset of vertical flow.

PMID- 14726587
TI  - Siberian peatlands a net carbon sink and global methane source since the early
      Holocene.
AB  - Interpolar methane gradient (IPG) data from ice cores suggest the "switching on"
      of a major Northern Hemisphere methane source in the early Holocene. Extensive
      data from Russia's West Siberian Lowland show (i) explosive, widespread peatland
      establishment between 11.5 and 9 thousand years ago, predating comparable
      development in North America and synchronous with increased atmospheric methane
      concentrations and IPGs, (ii) larger carbon stocks than previously thought (70.2
      Petagrams, up to approximately 26% of all terrestrial carbon accumulated since
      the Last Glacial Maximum), and (iii) little evidence for catastrophic oxidation,
      suggesting the region represents a long-term carbon dioxide sink and global
      methane source since the early Holocene.

PMID- 14726588
TI  - Community assembly through adaptive radiation in Hawaiian spiders.
AB  - Communities arising through adaptive radiation are generally regarded as unique,
      with speciation and adaptation being quite different from immigration and
      ecological assortment. Here, I use the chronological arrangement of the Hawaiian
      Islands to visualize snapshots of evolutionary history and stages of community
      assembly. Analysis of an adaptive radiation of habitat-associated, polychromatic
      spiders shows that (i) species assembly is not random; (ii) within any community,
      similar sets of ecomorphs arise through both dispersal and evolution; and (iii)
      species assembly is dynamic with maximum species numbers in communities of
      intermediate age. The similar patterns of species accumulation through
      evolutionary and ecological processes suggest universal principles underlie
      community assembly.

PMID- 14726589
TI  - Guar seed beta-mannan synthase is a member of the cellulose synthase super gene
      family.
AB  - Genes for the enzymes that make plant cell wall hemicellulosic polysaccharides
      remain to be identified. We report here the isolation of a complementary DNA
      (cDNA) clone encoding one such enzyme, mannan synthase (ManS), that makes the
      beta-1, 4-mannan backbone of galactomannan, a hemicellulosic storage
      polysaccharide in guar seed endosperm walls. The soybean somatic embryos
      expressing ManS cDNA contained high levels of ManS activities that localized to
      Golgi. Phylogenetically, ManS is closest to group A of the cellulose synthase
      like (Csl) sequences from Arabidopsis and rice. Our results provide the
      biochemical proof for the involvement of the Csl genes in beta-glycan formation
      in plants.

PMID- 14726590
TI  - A new strategy for the synthesis of glycoproteins.
AB  - Posttranslational modifications of proteins regulate many biological processes,
      including metabolism, signal transduction, and gene expression. The synthetic
      challenges associated with generating homogeneous populations of selectively
      modified proteins, however, have hindered detailed studies of the effects of
      these modifications on protein structure and function. Here, we report an
      approach to the cotranslational synthesis of selectively glycosylated proteins in
      which the modified amino acid is genetically encoded. We show that myoglobin
      containing beta-N-acetylglucosamine (GlcNAc)-serine at a defined position can be
      expressed in Escherichia coli in good yield and with high fidelity. The beta
      GlcNAc moiety can be recognized by a saccharide-binding protein, or subsequently
      modified with a galactosyltransferase to build more complex carbohydrates. This
      approach should be generally applicable to other posttranslational modifications
      such as protein phosphorylation, acetylation, and methylation.

PMID- 14726591
TI  - Heterodimeric GTPase core of the SRP targeting complex.
AB  - Two structurally homologous guanosine triphosphatase (GTPase) domains interact
      directly during signal recognition particle (SRP)-mediated cotranslational
      targeting of proteins to the membrane. The 2.05 angstrom structure of a complex
      of the NG GTPase domains of Ffh and FtsY reveals a remarkably symmetric
      heterodimer sequestering a composite active site that contains two bound
      nucleotides. The structure explains the coordinate activation of the two GTPases.
      Conformational changes coupled to formation of their extensive interface may
      function allosterically to signal formation of the targeting complex to the
      signal-sequence binding site and the translocon. We propose that the complex
      represents a molecular "latch" and that its disengagement is regulated by
      completion of assembly of the GTPase active site.

PMID- 14726592
TI  - Computational constraints on syntactic processing in a nonhuman primate.
AB  - The capacity to generate a limitless range of meaningful expressions from a
      finite set of elements differentiates human language from other animal
      communication systems. Rule systems capable of generating an infinite set of
      outputs ("grammars") vary in generative power. The weakest possess only local
      organizational principles, with regularities limited to neighboring units. We
      used a familiarization/discrimination paradigm to demonstrate that monkeys can
      spontaneously master such grammars. However, human language entails more
      sophisticated grammars, incorporating hierarchical structure. Monkeys tested with
      the same methods, syllables, and sequence lengths were unable to master a grammar
      at this higher, "phrase structure grammar" level.

PMID- 14726593
TI  - Differential representation of perception and action in the frontal cortex.
AB  - A motor illusion was created to separate human subjects' perception of arm
      movement from their actual movement during figure drawing. Trajectories
      constructed from cortical activity recorded in monkeys performing the same task
      showed that the actual movement was represented in the primary motor cortex,
      whereas the visualized, presumably perceived, trajectories were found in the
      ventral premotor cortex. Perception and action representations can be
      differentially recognized in the brain and may be contained in separate
      structures.

PMID- 14726594
TI  - Multiple Ebola virus transmission events and rapid decline of central African
      wildlife.
AB  - Several human and animal Ebola outbreaks have occurred over the past 4 years in
      Gabon and the Republic of Congo. The human outbreaks consisted of multiple
      simultaneous epidemics caused by different viral strains, and each epidemic
      resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass.
      These animal populations declined markedly during human Ebola outbreaks,
      apparently as a result of Ebola infection. Recovered carcasses were infected by a
      variety of Ebola strains, suggesting that Ebola outbreaks in great apes result
      from multiple virus introductions from the natural host. Surveillance of animal
      mortality may help to predict and prevent human Ebola outbreaks.

PMID- 14726595
TI  - Satellite measurements reveal persistent small-scale features in ocean winds.
AB  - Four-year averages of 25-kilometer-resolution measurements of near-surface wind
      speed and direction over the global ocean from the QuikSCAT satellite radar
      scatterometer reveal the existence of surprisingly persistent small-scale
      features in the dynamically and thermodynamically important curl and divergence
      of the wind stress. Air-sea interaction over sea surface temperature fronts
      throughout the world ocean is evident in both the curl and divergence fields, as
      are the influences of islands and coastal mountains. Ocean currents such as the
      Gulf Stream generate distinctive patterns in the curl field. These previously
      unresolved features have important implications for oceanographic and air-sea
      interaction research.

PMID- 14726596
TI  - EGF-like growth factors as mediators of LH action in the ovulatory follicle.
AB  - Before ovulation in mammals, a cascade of events resembling an inflammatory
      and/or tissue remodeling process is triggered by luteinizing hormone (LH) in the
      ovarian follicle. Many LH effects, however, are thought to be indirect because of
      the restricted expression of its receptor. Here, we demonstrate that LH
      stimulation induces the transient and sequential expression of the epidermal
      growth factor (EGF) family members amphiregulin, epiregulin, and beta-cellulin.
      Incubation of follicles with these growth factors recapitulates the morphological
      and biochemical events triggered by LH, including cumulus expansion and oocyte
      maturation. Thus, these EGF-related growth factors are paracrine mediators that
      propagate the LH signal throughout the follicle.

PMID- 14726597
TI  - Functional dissection of the interactions of stonin 2 with the adaptor complex AP
      2 and synaptotagmin.
AB  - Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis.
      This process involves the coordinated assembly of clathrin and adaptor proteins
      and the concomitant selection of cargo proteins. Here, we demonstrate that the
      endocytotic protein stonin 2 localizes to axonal vesicle clusters through its
      micro-homology domain. Interaction of this domain with synaptotagmin I is
      sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of
      stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin
      adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable
      of binding to the alpha-adaptin ear domain and to micro2. Mutation of the
      tyrosine motif-binding pocket of micro2 abolishes recognition of the WVxF
      peptide, suggesting that association with stonin 2 renders AP-2 incompetent to
      sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may
      function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.

PMID- 14726598
TI  - Nutritional genomics.
AB  - The integration of genomics into nutritional sciences has illuminated the
      complexity of genome responses to nutritional exposures while offering
      opportunities to increase the effectiveness of nutritional interventions, both
      clinical and population based. Nutrients elicit multiple physiological responses
      that affect genome stability, imprinting, expression, and viability. These
      effects confer both health benefits and risks, some of which may not become
      apparent until later in life. Nutritional genomics challenges us to understand
      the reciprocal and complex interactions among the human genome and dietary
      components in normal physiology and pathophysiology. Understanding these
      interactions will refine current definitions of benefit and risk and lead to the
      establishment of dietary recommendations that have a high predictive value,
      minimize the risk of unintended consequences, and account for the modifying
      effects of human genetic variation. Furthermore, nutritional genomics will enable
      the design of effective dietary regimens for the prevention and management of
      complex chronic disease. This review focuses on new perspectives that have been
      presented to the nutritional sciences by the advent of genomics, and new
      challenges that demand attention because of their potential impact on, and
      immediate translation into, current public health nutrition recommendations and
      interventions.

PMID- 14726599
TI  - Nutritional genomics: the next frontier in the postgenomic era.
AB  - The interface between the nutritional environment and cellular/genetic processes
      is being referred to as "nutrigenomics." Nutrigenomics seeks to provide a
      molecular genetic understanding for how common dietary chemicals (i.e.,
      nutrition) affect health by altering the expression and/or structure of an
      individual's genetic makeup. The fundamental concepts of the field are that the
      progression from a healthy phenotype to a chronic disease phenotype must occur by
      changes in gene expression or by differences in activities of proteins and
      enzymes and that dietary chemicals directly or indirectly regulate the expression
      of genomic information. We present a conceptual basis and specific examples for
      this new branch of genomic research that focuses on the tenets of nutritional
      genomics: 1) common dietary chemicals act on the human genome, either directly or
      indirectly, to alter gene expression or structure; 2) under certain circumstances
      and in some individuals, diet can be a serious risk factor for a number of
      diseases; 3) some diet-regulated genes (and their normal, common variants) are
      likely to play a role in the onset, incidence, progression, and/or severity of
      chronic diseases; 4) the degree to which diet influences the balance between
      healthy and disease states may depend on an individual's genetic makeup; and 5)
      dietary intervention based on knowledge of nutritional requirement, nutritional
      status, and genotype (i.e., "individualized nutrition") can be used to prevent,
      mitigate, or cure chronic disease.

PMID- 14726600
TI  - Understanding renal and cardiovascular function through physiological genomics.

PMID- 14726601
TI  - Making sense of an alphabet soup: the use of a new bioinformatics tool for
      identification of novel gene islands. Focus on "identification of genomic islands
      in the genome of Bacillus cereus by comparative analysis with Bacillus
      anthracis".

PMID- 14726602
TI  - From SNPs to function: the effect of sequence variation on gene expression. Focus
      on "a survey of genetic and epigenetic variation affecting human gene
      expression".

PMID- 14726603
TI  - Developmental changes in the fetal pig transcriptome.
AB  - Growth and development of pig fetuses is dependent on the coordinated expression
      of multiple genes. Between 21 and 45 days of gestation, fetuses experience
      increasing growth rates that can result in uterine crowding and increased
      mortality. We used differential display reverse transcription-PCR (DDRT-PCR) to
      identify differentially expressed genes in pig fetuses at 21, 35, and 45 days of
      gestation. Pig cDNAs were identified with homologies to CD3 gamma-subunit,
      collagen type XIV alpha1, complement component C6, craniofacial developmental
      protein 1, crystallin-gammaE, DNA binding protein B, epsilon-globin, formin
      binding protein 2, ribosomal protein L23, small acidic protein, secreted frizzled
      related protein 2, titin, vitamin D binding protein, and two hypothetical protein
      products. Two novel expressed sequence tags (ESTs) were also identified.
      Expression patterns were confirmed for eight genes, and spatiotemporal expression
      of three genes was evaluated. We identified novel transcriptome changes in fetal
      pigs during a period of rapid growth. These changes involved genes with a
      spectrum of proposed functions, including musculoskeletal growth, immune system
      function, and cellular regulation. This information can ultimately be used to
      enhance production efficiency through improved pig growth and survival.

PMID- 14726604
TI  - Nitric oxide and superoxide in inflammation and immune regulation.
AB  - Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects
      on inflammation and play a key role in the regulation of immune responses. They
      affect virtually every step of the development of inflammation. Low
      concentrations of nitric oxide produced by constitutive and neuronal nitric oxide
      synthases inhibit adhesion molecule expression, cytokine and chemokine synthesis
      and leukocyte adhesion and transmigration. Large amounts of NO, generated
      primarily by iNOS can be toxic and pro-inflammatory. Actions of nitric oxide are
      however not dependent primarily on the enzymatic source, but rather on the
      cellular context, NO concentration (dependent on the distance from NO source) and
      initial priming of immune cells. These observations may explain difficulties in
      determining the exact role of NO in Th1 and Th2 lymphocyte balance in normal
      immune responses and in allergic disease. Similarly superoxide anion produced by
      NAD(P)H oxidases present in all cell types participating in inflammation
      (leukocytes, endothelial and other vascular cells etc) may lead to toxic effects,
      when produced at high levels during oxidative burst, but may also modulate
      inflammation in a far more discrete way, when continuously produced at low levels
      by NOXs (non-phagocytic oxidases). The effects of both nitric oxide and
      superoxide in immune regulation are exerted through multiple mechanisms, which
      include interaction with cell signalling systems like cGMP, cAMP, G-protein,
      JAK/STAT or MAPK dependent signal transduction pathways. They may also lead to
      modification of transcription factors activity and in this way modulate the
      expression of multiple other mediators of inflammation. Moreover genetic
      polymorphisms exist within genes encoding enzymes producing both NO and
      superoxide. The potential role of these polymorphisms in inflammation and
      susceptibility to infection is discussed. Along with studies showing increasing
      role of NO and free radicals in mediating inflammatory responses drugs which
      interfere with these systems are being introduced in the treatment of
      inflammation. These include statins, angiotensin receptor blockers, NAD(P)H
      oxidase inhibitors, NO-aspirin and others. In conclusion in this mini-review we
      discuss the mechanisms of nitric oxide and superoxide dependent modulation of
      inflammatory reactions in experimental animals and humans. We also discuss
      potential roles of nitric oxide as a mediator of allergic inflammation.

PMID- 14726605
TI  - Regulation of expression of stromyelysin-1 by proinflammatory cytokines in mouse
      brain astrocytes.
AB  - Stromelysin-1 belongs to matrix metalloproteinases responsible for proteolytic
      degradation of extracellular matrix in many tissues during various diseases,
      especially those involving inflammation. We studied the induced expression of
      stromelysin-1 in primary cultures of mouse brain astrocytes stimulated with
      various cytokines and cellular growth factors. Interleukin-1-beta (IL-1beta),
      tumor necrosis factor alpha (TNFalpha) and a mixture of IL-1, TNF and epidermal
      growth factor (EGF) significantly increased the level of stromelysin-1 mRNA in
      mouse astrocytes while interferon-gamma (IFN-gamma) inhibited this response or
      was without effect. This accumulation of specific mRNA was preceded by activation
      of two examined transcription factors: NFkappaB and AP-1. However, experiments
      with known inhibitors of activation of these transcription factors: pyrrolidine
      dithiocarbamate (PDTC), parthenolide and curcumin, indicate that NFkappaB and AP
      1 cannot be solely responsible for the cytokine induced expression of stromelysin
      1 gene in mouse astrocytes.

PMID- 14726606
TI  - Atrial natriuretic peptide ameliorates hypoxic pulmonary vasoconstriction without
      influencing systemic circulation.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is encountered during ascent to high
      altitude. Atrial natriuretic peptide (ANP) could be an option to treat HPV
      because of its natriuretic, diuretic, and vasodilatory properties. Data on
      effects of ANP on pulmonary and systemic circulation during HVP are conflicting,
      partly owing to anesthesia, surgical stress or uncontrolled dietary conditions.
      Therefore, ten conscious, chronically tracheotomized dogs were studied under
      standardized dietary conditions. The dogs were trained to breathe spontaneously
      at a ventilator circuit. PROTOCOL: 30min of normoxia [inspiratory oxygen fraction
      (F(i)O(2))=0.21] were followed by 30min of hypoxia without ANP infusion (Hypoxia
      I, F(i)O(2)=0.1). While maintaining hypoxia an intravenous infusion of atrial
      natriuretic peptide was started with 50ng x kg body wt(-1) x min(-1) for 30min
      (Hypoxia+ANP1=low dose), followed by 1000ng x kg body wt(-1) x min(-1) for 30min
      (Hypoxia+ANP2=high dose). Thereafter, ANP infusion was stopped and hypoxia
      maintained for a final 30min (Hypoxia II). Compared to normoxia, mean pulmonary
      arterial pressure (MPAP) (16+/-0.7 vs. 26+/-1.3mmHg) and pulmonary vascular
      resistance (PVR) (448+/-28 vs. 764+/-89dyn x s(-1) x cm(-5)) increased during
      Hypoxia I and decreased during Hypoxia+ANP 1 (MPAP 20+/-1mmHg, PVR 542+/-55dyn x
      s(-1) x cm(-5)) (P<0.05). The higher dose of ANP did not further decrease MPAP or
      PVR, but started to have a tendency to decrease mean arterial pressure and
      cardiac output. We conclude that low dose ANP is able to reduce HPV without
      affecting systemic circulation during acute hypoxia.

PMID- 14726607
TI  - Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not
      mediated by endothelial alpha2 adrenoceptors.
AB  - Functional role of endothelial alpha(2)-adrenoceptor in coronary circulation
      remains unclear. Clonidine, an agonist of alpha(2)-adrenoceptors, was reported to
      induce coronary vasodilatation via stimulation of endothelial alpha(2)
      adrenoceptors or coronary vasoconstriction involving vascular smooth muscle
      alpha(2)-adrenoceptors. Moreover, H(2) receptor-dependent responses to clonidine
      were described. Here, we reassess the contribution of endothelial alpha(2)
      adrenoceptor and H(2) receptors to coronary flow and contractility responses
      induced by clonidine in the isolated guinea pig heart. We found that clonidine
      (10(-9) - 10(-6) M) produced concentration-dependent coronary vasoconstriction
      without a significant change in contractility. This response was inhibited by the
      alpha(1)/alpha(2)-adrenoceptor antagonist - phentolamine (10(-5) M) and the
      selective alpha(2)-adrenoceptor antagonist yohimbine (10(-6) M), but it was not
      changed by the selective alpha(1)-adrenoceptor antagonist prazosin (10(-6) M). In
      the presence of nitric oxide synthase inhibitor, L-NAME (10(-4) M) the clonidine
      induced vasoconstriction was potentiated. Clonidine at high concentrations of 10(
      5) - 3 x 10(-5) M produced coronary vasodilatation, and an increase in myocardial
      contractility. These responses were abolished by a selective H(2)-receptor
      antagonist, ranitidine (10(-5) M), but not by phentolamine (10(-5) M). We
      conclude that in the isolated guinea pig heart, clonidine-induced
      vasoconstriction is mediated by activation of smooth muscle alpha(2)
      adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by
      activation of vascular H(2) histaminergic receptors. Accordingly, endothelial
      alpha(2)-adrenoceptors does not seem to play a major role in coronary flow
      response induced by clonidine.

PMID- 14726608
TI  - Vitamin A deficiency alters the bioelectric parameters and RNA content of rat
      gastric mucosa in vitro.
AB  - The present study was aimed to investigate the mechanisms by which vitamin A
      plays a role in maintaining the efficiency of gastric mucosal barrier.
      Particularly, we measured electrical parameters and the RNA/DNA ratio of gastric
      mucosa isolated in vitro from the stomach of rats in which vitamin A-deficiency
      was induced by means of a vitamin A-free diet and then abolished by means of a
      massive vitamin A supplementation. Pair-fed vitamin A-nondepleted rats and normal
      rats fed ad libitum on a standard diet served as controls. Vitamin A status was
      assayed for each group of rats by measuring the hepatic content of vitamin A. We
      found that in gastric mucosa vitamin A-deficiency induced: 1) a decrease in both
      transmucosal potential difference and short-circuit current; 2) an increase in
      transmucosal electrical resistance; 3) a decrease in RNA content resulting in a
      decreased RNA/DNA ratio. Abolishment of vitamin A-deficiency restored both
      electrical parameters and RNA content of rat gastric mucosa. Our results stress
      the role of vitamin A in maintaining the efficiency of the gastric mucosal
      barrier. Vitamin A seems to act by stabilizing gastric electrical parameters and
      by controlling the protein synthesis/turnover in the surface gastric mucosal
      cells.

PMID- 14726609
TI  - Lipidomic processes in homeostatic and LPS-modified cell renewal cycle. Role of
      phosphatidylinositol 3-kinase pathway in biomembrane synthesis and restitution of
      apical epithelial membrane.
AB  - BACKGROUND: Nuclear transcriptome initiates specific proteome that facilitates
      metabolic events culminating in restitution of cell components and reproduction
      of the discrete cellular function, but the magnitude of various genes induction
      and following proteomic, lipidomic, and glycomic processes provide distinctness
      to the final product and its function. In homeostasis, the challenged cell
      responds to stimuli in defined and predictable mode but in the disease such as
      ulcerative erosions the ablation of cell survival signals and cell apoptosis is
      enhanced. Therefore, to uncover the discreteness and dissimilarity of the
      pathological processes induced by elicobacter pylori (H. pylori)
      lipopolysaccharide (LPS), not only measurement of the genomic events is crucial,
      but a complete cycle of events reproducing the cell specific proteins, lipids,
      and cell-specific environment created in situ require thorough investigation.
      METHODS: An impact of H. pylori LPS-induced processes on posttranslational
      lipidomic activity in endoplasmic reticulum (ER), Golgi and apical membrane was
      evaluated in the in vitro paradigm assembled with components of the rat gastric
      mucosal epithelial cells. RESULTS: In ER, the signals commanding synthesis of
      biomembrane in the presence of control, the LPS-derived or LPS-admixed cytosol
      was identical. The assembled vesicles contained the same amount of apoprotein and
      had the same lipid composition. Their biomembrane contained the same amount of
      sphingolipids in form of ceramide, which is determining factor of the ER
      transport vesicle completion. The transport of apoprotein in ER vesicles to Golgi
      was also not changed. In Golgi, LPS-derived cytosol affected two distinct and
      concurrent with assembly of Golgi transport vesicles processes. The LPS-derived
      cytosol affected formation of Golgi transport vesicles destined to apical
      membrane and the incorporation (fusion) of Golgi vesicles with apical epithelial
      membrane. The LPS-derived cytosol decreased the production of Golgi vesicles by
      15% and their fusion with the apical epithelial membrane by 83%. In contrast with
      wortmannin, the LPS-derived cytosol had no impact on Golgi transport vesicles
      association with the epithelial membrane. CONCLUSIONS: We concluded that LPS
      interferes with MAPK-dependent activation of cytosolic PLA(2) since MAPKs
      immunoprecipitate added to the LPS-cytosol restored activation of cytosolic
      PLA(2)-specific fusion of the Golgi transport vesicles with apical mucosal cell
      membrane. On the other hand, wortmannin that inhibited the association of Golgi
      transport vesicles with apical membrane, interferes with cytosolic activity that
      controls association of PI3K-containing Golgi vesicles with the apical membrane.
      Together, our studies present evidence that allow to conclude that LPS affects
      MAPK-specific phosphorylation and PLA(2)-assisted membranes' fusion, whereas
      wortmannin affects association of PI3K- and PI3P-containing Golgi-derived
      transport vesicles with the membrane. In the final outcome, both actions result
      in a diminished or inhibited restitution of apical membrane.

PMID- 14726610
TI  - Influence of the stimulation of central chemoreceptors on the gastric mucosal
      blood flow in artificially ventilated and spontaneously breathing rats.
AB  - Respiratory failure coincides frequently with the occurrence of gastric
      ulceration. In advanced respiratory insufficiency hypoxemia is often accompanied
      by hypercapnia, which is the stimulus for central chemoreceptors as well as for
      carotid body chemoreceptors. The purpose of the work was to investigate the
      reflex effect of stimulation of central chemoreceptors on gastric mucosal blood
      flow (GMBF) in the rat. Central chemoreceptors were stimulated by a gas mixture
      composed of 10% carbon dioxide, 50% oxide and 40% nitrogen. In artificially
      ventilated and spontaneously breathing animals, the stimulation of central
      chemoreceptors caused a significant increase in gastric mucosal vascular
      resistance, accompanied by a marked decline in blood flow. We hypothesize that in
      patients with respiratory insufficiency accompanied by hypercapnia, the reflex
      impairment of GMBF may contribute to gastric ulceration.

PMID- 14726611
TI  - Ghrelin attenuates the development of acute pancreatitis in rat.
AB  - BACKGROUND: Ghrelin, a circulating growth hormone-releasing peptide isolated from
      human and rat stomach, stimulates growth hormone secretion, food intake and
      exhibits gastroprotective properties. Ghrelin is predominantly produced by a
      population of endocrine cells in the gastric mucosa, but its presence in bowel,
      pancreas, pituitary and hypothalamus has been reported. In human fetal pancreas,
      ghrelin is expressed in a prominent endocrine cell population. In adult
      pancreatic islets the population of these cell is reduced. The aim of present
      study was to investigate the influence of ghrelin administration on the
      development of acute pancreatitis. METHODS: Acute pancreatitis was induced in rat
      by caerulein injection. Ghrelin was administrated twice (30 min prior to the
      first caerulein or saline injection and 3 h later) at the doses: 2, 10 or 20
      nmol/kg. Immediately after cessation of caerulein or saline injections the
      following parameters were measured: pancreatic blood flow, plasma lipase
      activity, plasma interleukin-1beta (IL-1beta) and interleukin 10 (IL-10)
      concentration, pancreatic DNA synthesis, and morphological signs of pancreatitis.
      RESULTS: Administration of ghrelin without induction of pancreatitis did not
      affect significantly any parameter tested. Caerulein led to the development of
      acute edematous pancreatitis. Treatment with ghrelin at the dose 2 nmol/kg,
      during induction of pancreatitis, was without effect on pancreatic histology or
      biochemical and functional parameters. Treatment with ghrelin at the dose 10 and
      20 nmol/kg attenuated the development of pancreatitis and the effects of both
      doses were similar. Administration of ghrelin (10 or 20 nmol/kg) reduced
      inflammatory infiltration of pancreatic tissue and vacuolization of acinar cells.
      Also, plasma lipase activity and plasma IL-1beta concentration were reduced, and
      caerulein-induced fall in pancreatic DNA synthesis was reversed. Administration
      of ghrelin at the dose 10 and 20 nmol/kg was without effect on caerulein-induced
      pancreatic edema and pancreatitis-related fall in pancreatic blood flow.
      CONCLUSIONS: (1) Administration of ghrelin attenuates pancreatic damage in
      caerulein-induced pancreatitis; (2) Protective effect of ghrelin administration
      seems Background: Ghrelin, a circulating growth hormone-releasing peptide
      isolated from human and rat stomach, stimulates growth hormone secretion, food
      intake and exhibits gastroprotective properties. Ghrelin is predominantly
      produced by a population of endocrine cells in the gastric mucosa, but its
      presence in bowel, pancreas, pituitary and hypothalamus has been reported. In
      human fetal pancreas, ghrelin is expressed in a prominent endocrine cell
      population. In adult pancreatic islets the population of these cell is reduced.
      The aim of present study was to investigate the influence of ghrelin
      administration on the development of acute pancreatitis. Methods: Acute
      pancreatitis was induced in rat by caerulein injection. Ghrelin was administrated
      twice (30 min prior to the first caerulein or saline injection and 3 h later) at
      the doses: 2, 10 or 20 nmol/kg. Immediately after cessation of caerulein or
      saline injections the following parameters were measured: pancreatic blood flow,
      plasma lipase activity, plasma interleukin-1beta (IL-1beta) and interleukin 10
      (IL-10) concentration, pancreatic DNA synthesis, and morphological signs of
      pancreatitis. Results: Administration of ghrelin without induction of
      pancreatitis did not affect significantly any parameter tested. Caerulein led to
      the development of acute edematous pancreatitis. Treatment with ghrelin at the
      dose 2 nmol/kg, during induction of pancreatitis, was without effect on
      pancreatic histology or biochemical and functional parameters. Treatment with
      ghrelin at the dose 10 and 20 nmol/kg attenuated the development of pancreatitis
      and the effects of both doses were similar. Administration of ghrelin (10 or 20
      nmol/kg) reduced inflammatory infiltration of pancreatic tissue and vacuolization
      of acinar cells. Also, plasma lipase activity and plasma IL-1beta conc;
      concentration were reduced, and caerulein-induced fall in pancreatic DNA
      synthesis was reversed. Administration of ghrelin at the dose 10 and 20 nmol/kg
      was without effect on caerulein-induced pancreatic edema and pancreatitis-related
      fall in pancreatic blood flow. Conclusions: (1) Administration of ghrelin
      attenuates pancreatic damage in caerulein-induced pancreatitis; (2) Protective
      effect of ghrelin administration seems to be related the inhibition in
      inflammatory process and the reduction in liberation of pro-inflammatory IL
      1beta.

PMID- 14726612
TI  - IGF-1 stimulates production of interleukin-10 and inhibits development of
      caerulein-induced pancreatitis.
AB  - BACKGROUND/AIM: Insulin-like growth factor-1 (IGF-1) and other growth factors
      overexpression was reported in acute pancreatitis. Previous studies have shown
      the protective effect of epidermal growth factor (EGF), Hepatocyte Growth Factor
      (HGF) and Fibroblast Growth Factor (FGF) in the course of experimental acute
      pancreatitis. The aim of our studies was to determine the effect of IGF-1
      administration on the development of caerulein-induced pancreatitis. METHODS:
      Acute pancreatitis was induced by infusion of caerulein (10 micro/kg/h) for 5 h.
      IGF-1 was administrated twice at the doses: 2, 10, 50, or 100 micro/kg s.c.
      RESULTS: Administration of IGF-1 without induction of pancreatitis increased
      plasma interleukin-10 (IL-10). Infusion of caerulein led to development of acute
      edematous pancreatitis. Histological examination showed pancreatic edema,
      leukocyte infiltration and vacuolization of acinar cells. Also, acute
      pancreatitis led to an increase in plasma lipase and interleukin 1beta (IL-1beta)
      level, whereas pancreatic DNA synthesis and pancreatic blood flow were decreased.
      Treatment with IGF-1, during induction of pancreatitis, increased plasma IL-10
      and attenuated the pancreatic damage, what was manifested by histological
      improvement of pancreatic integrity, the partial reversion of the drop in
      pancreatic DNA synthesis and pancreatic blood flow, and the reduction in
      pancreatitis-evoked increase in plasma amylase, lipase and IL-1beta level.
      Protective effect of IGF-1 administration was dose-dependent. Similar strong
      protective effect was observed after IGF-1 at the dose 2 x 50 and 2 x 100
      microg/kg. CONCLUSIONS: (1) Administration of IGF-1 attenuates pancreatic damage
      in caerulein-induced pancreatitis; (2) This effect is related, at least in part,
      to the increase in IL-10 production, the reduction in liberation of IL-1beta and
      the improvement of pancreatic blood flow.

PMID- 14726614
TI  - Effects of vagal neuromodulation and vagotomy on control of food intake and body
      weight in rats.
AB  - Food induced neurohumoral signals are conduced to data processing brain centers
      mainly as vagal afferent discharge resulting in food intake regulation. The aim
      of this study was to evaluate effects of vagal nerve neuromodulation in control
      of food intake with fed-pattern microchip (MC) pacing. Experiments were performed
      on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of
      both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of
      both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was
      combined with right side abdominal vagotomy. Body weight and total food intake
      decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV),
      38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation
      on final body weight and food intake was significantly more effective than only
      single nerve MC pacing however most effective was stimulation with 0,1Hz combined
      with right vagotomy. We conclude that vagal stimulation reduce food intake and
      body weight by increasing vagal afferent signals. Our results suggest that
      information in vagal afferents can be modulated resulting in changes of feeding
      behaviour and body weight.

PMID- 14726613
TI  - Role of leptin in the control of postprandial pancreatic enzyme secretion.
AB  - Leptin released by adipocytes has been implicated in the control of food intake
      but recent detection of specific leptin receptors in the pancreas suggests that
      this peptide may also play some role in the modulation of pancreatic function.
      This study was undertaken to examine the effect of exogenous leptin on pancreatic
      enzyme secretion in vitro using isolated pancreatic acini, or in vivo in
      conscious rats with chronic pancreatic fistulae. Leptin plasma level was measured
      by radioimmunoassay following leptin administration to the animals.
      Intraperitoneal (i.p.) administration of leptin (0.1, 1, 5, 10, 20 or 50
      microg/kg), failed to affect significantly basal secretion of pancreatic protein,
      but markedly reduced that stimulated by feeding. The strongest inhibition has
      been observed at dose of 10 microg/kg of leptin. Under basal conditions plasma
      leptin level averaged about 0.15 +/- 0.04 ng/ml and was increased by feeding up
      to 1.8 +/- 0.4 ng/ml. Administration of leptin dose-dependently augmented this
      plasma leptin level, reaching about 0.65 +/- 0.04 ng/ml at dose of 10 microg/kg
      of leptin. This dose of leptin completely abolished increase of pancreatic
      protein output produced by ordinary feeding, sham feeding or by diversion of
      pancreatic juice to the exterior. Leptin (10(-10)-10(-7) M) also dose-dependently
      attenuated caerulein-induced amylase release from isolated pancreatic acini,
      whereas basal enzyme secretion was unaffected. We conclude that leptin could take
      a part in the inhibition of postprandial pancreatic secretion and this effect
      could be related, at least in part, to the direct action of this peptide on
      pancreatic acini.

PMID- 14726615
TI  - Short, 12 mer fluorescently labeled methylphosphonated oligonucleotides to
      visualize beta-actin MRNA in vivo.
AB  - A pair of fluorescently labeled antisense ( complementary to beta-actin mRNA) or
      control methylphosphonated DNA 12-mers were introduced into live cells. After
      fixation their distribution throughout the cell was compared to the localization
      pattern for the pair of control oligos.The distribution of the two sets of oligos
      differed in that there was a distinct pool of antisense probes that were detected
      at elevated levels in the leading edge of fibroblast and cortical underlining.
      The resulting fluorescence patterns of antisense probes colocalized and were
      analogous to labeling pattern already described and produced by in situ
      hybridization. The length of each of the probe destabilized binding to mismatched
      sequences at physiological temperature, while the overall length of the pair gave
      a unique, highly sequence specific recognition of a target sequence.
      Simultaneous, in vivo application of multiple probes let include internal
      controls into the experimental setup, in order to distinguish different
      distributions of antisense and control probes in the same specimen.

PMID- 14726616
TI  - Centrally administered galanin modifies vasopressin and oxytocin release from the
      hypothalamo-neurohypophysial system of euhydrated and dehydrated rats.
AB  - Galanin (Gal) as a neuropeptide with widespread distribution in the central
      nervous system may be involved in the mechanisms of vasopressin (AVP) and
      oxytocin (OT) release from the hypothalamo-neurohypophysial system. Vasopressin
      and oxytocin content in the hypothalamus and neurohypophysis as well as plasma
      level of both neurohormones were studied after galanin treatment in euhydrated
      and dehydrated rats. In not dehydrated rats intracerebroventricular (i.c.v.)
      injections of Gal did not affect the hypothalamic and neurohypophysial OT
      content, however, distinctly increased plasma OT concentration. In the same
      animals Gal diminished the hypothalamic AVP content but was without the effect on
      neurohypophysial AVP storage; plasma AVP level then raised. Galanin, administered
      i.c.v. to rats deprived of water, distinctly inhibited AVP and OT release from
      the hypothalamo-neurohypophysial system. Simultaneously, plasma AVP and OT level
      was significantly diminished after Gal treatment in dehydrated rats. These
      results suggest that modulatory effect of galanin on vasopressin and oxytocin
      release depends on the actual state of water metabolism. Gal acts as an
      inhibitory neuromodulator of AVP and OT secretion under conditions of the
      dehydration but stimulates this process in the state of equilibrated water
      metabolism.

PMID- 14726617
TI  - Influence of cyclooxygenase inhibitors on the central histaminergic stimulations
      of hypothalamic - pituitary - adrenal axis.
AB  - Brain histamine participates in central regulation of the hypothalamic-pituitary
      adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of
      different neurotransmitters involved in activation of HPA axis. In the present
      experiment we investigated whether endogenous prostaglandins are involved in the
      stimulation of ACTH and corticosterone secretion by histaminergic systems in the
      rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative
      (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50
      microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non
      anesthetized rats considerably increased ACTH and corticosterone secretion 1h
      after administration. A non-selective cyclooxygenase inhibitor indomethacin (2
      mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more
      potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1
      and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2)
      were given 15 min before histamine and histamine receptor agonists. One hour
      after the last injection trunk blood from decapitated rats was collected for
      hormones determination. The histamine-induced ACTH and corticosterone secretion
      was significantly diminished by piroxicam and was not markedly altered by
      indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and
      corticosterone secretion was significantly prevented by indomethacin and was not
      affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH
      and corticosterone secretion was not markedly influenced by any cyclooxygenase
      blocker applied in the present experiment. These results indicate that the
      histamine H(1)-receptor transmitted central stimulation of the HPA axis is
      considerably mediated by prostaglandins generated by consititutive
      cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not
      significantly depend on endogenous prostaglandins mediation.

PMID- 14726618
TI  - Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice.
AB  - Several studies have reported the anxiolytic-like effects of various nitric oxide
      synthase inhibitors in distinct animal models. However, in the context of
      anxiety, the possible involvement of cyclic GMP, believed to be one of the main
      targets of NO, remains obscure. Cyclic GMP is degraded by the specific
      phosphodiesterases in the brain. Therefore, we studied the effect of the
      selective phosphodiesterase type 5 inhibitor sildenafil in the mouse elevated
      plus-maze test of anxiety and in the open field test of locomotion. We found that
      sildenafil (0.05-10 mg/kg i.p.) alone did not affect the behavior of animals in
      the plus-maze or open field tests, but the anxiogenic beta-carboline DMCM given
      in a subconvulsive dose (2 mg/kg i.p.) decreased the time spent on open arms in
      the elevated plus-maze. Treatment with the NO precursor L-arginine (200 mg/kg
      i.p.) did not modify the behavior of animals in the plus-maze, however, when
      sildenafil (1 mg/kg i.p.) was administered in combination with L-arginine (200
      mg/kg i.p.), both the time spent on the open arms and the percentage of open arm
      visits were significantly decreased. We conclude that augmentation of the NO-cGMP
      cascade induces anxiogenic-like effect in mice.

PMID- 14726619
TI  - Relationships of serum leptin levels with biochemical markers of bone turnover
      and with growth factors in normal weight and overweight children.
AB  - OBJECTIVE: To examine the hypothesis of an influence of leptin on growth factors
      and on biochemical markers of bone turnover of prepubertal overweight children.
      DESIGN AND METHODS: 395 prepubertal children, 6-13 years of age, were selected
      and the relationships between circulating serum levels of leptin and insulin-like
      growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and
      some biochemical markers of bone turnover (osteocalcin, OC; carboxyterminal
      propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I
      collagen, ICTP) were analyzed. The subjects were subdivided into normal weight
      (NW, n = 163) and weight excess (WE, n = 232) subjects. RESULTS AND CONCLUSIONS:
      Significant differences between the two groups were found for leptin (p < 0.01),
      IGF-I (p < 0.01) and IGFBP-3 (p < 0.01), with higher values in WEs, and for OC (p
      < 0.01) with higher values in NWs. A significant reduction of leptin (p < 0.01)
      and IGFBP-3 (p < 0.01) serum values and an increase of those of OC (p < 0.01) and
      PICP (p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in
      weight excess during a weight-excess reduction program. No variations were
      observed in 26 non-responsive subjects. In a multivariate analysis in which
      leptin, corrected by BMI and sex, was the independent variable, a significant
      negative correlation was found with PICP (beta = -0.235, p < 0.01), IGF-I (beta =
      -0.180, p < 0.01) and height velocity (beta = -0.155, p < 0.01). There was no
      correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional
      status and leptin levels are involved in the regulation of growth factors and
      biochemical markers of bone formation.

PMID- 14726620
TI  - Altered distribution of the debrisoquine oxidative phenotypes in children with
      type 1 diabetes mellitus.
AB  - OBJECTIVE: The recently observed increase in the incidence of type 1 diabetes
      mellitus (Type 1 DM) suggests a major role of environmental factors in the
      etiopathogenesis of the disease. The individual variation in cytochrome
      P(450)IID6 may influence the individual susceptibility to environmentally linked
      diseases. We aimed to evaluate the prevalence of cytochrome P(450)IID6 phenotypes
      in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n =
      100). METHODS: Debrisoquine was administered orally and debrisoquine
      hydroxylation phenotype was determined as a metabolic ratio of urinary recovered
      debrisoquine and 4-hydroxydebrisoquine. RESULTS: Eight of the 100 healthy
      subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome
      P(450)IID6 poor metabolizer phenotype (metabolic ratio > or =12.6). CONCLUSION:
      Cytochrome P(450)IID6's activity may play a role in the development of Type 1 DM.

PMID- 14726621
TI  - Can optimal primary cytoreduction be predicted in advanced stage epithelial
      ovarian cancer? Role of preoperative serum CA-125 level.
AB  - The aim of this study was to determine the ability of preoperative serum CA-125
      levels to predict optimal cytoreduction in patients with stage III epithelial
      ovarian cancer. A retrospective review was made of the records of 40 patients
      with FIGO stage III ovarian carcinoma who underwent primary cytoreductive
      surgery. A receiver operating characteristic (ROC) curve was used to determine
      the most useful CA-125 level in predicting optimal versus suboptimal tumour
      cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual
      disease <or=1 cm). A preoperative serum CA-125 level of 500 U/ml was found to be
      the value with the most predictive power. Optimal cytoreduction was obtained in
      16 of the 21 cases (76%) with a CA-125 <500 U/ml compared to only 6 of the 19
      cases (32%) with a CA-125 >500 U/ml. At this threshold, preoperative serum CA-125
      level was able to predict optimal versus suboptimal cytoreduction with a
      sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and
      negative predictive value of 76%. In the management of patients with advanced
      epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict
      optimal primary cytoreduction and to identify candidates for alternative
      approaches other than traditional primary cytoreductive surgery, such as
      neoadjuvant chemotherapy.

PMID- 14726622
TI  - Reduction of brain and sense organs in the fossil insular bovid Myotragus.
AB  - Our study of the fossil rupicaprine bovid Myotragus [Bate, 1909] from the
      Mediterranean island Majorca (Spain) provides evidence that this animal underwent
      significant changes (reduction) in the relative size of brain and sense organs
      after geographic isolation at the end of the Messinian Salinity Crisis (Miocene
      Pliocene boundary, 5.2 Mya). The changes in the central nervous system of
      Myotragus parallel the pattern reported for domesticated animals, in which
      decrease in relative brain size is accompanied by a decrease in the relative size
      of their sense organs. We interpret the important size reduction of brain and
      sense organs in Myotragus as an adaptive strategy for more efficient energy use
      under the special environmental conditions of the insular ecosystem,
      characterized by absence of predation and limitation of trophic resources.

PMID- 14726623
TI  - Social status interacts with badge size and neuroendocrine physiology to
      influence sexual behavior in male house sparrows (Passer domesticus).
AB  - Reproduction results from a complex interplay among multiple factors including
      social stimuli, hormones, the brain, and an individual's physical
      characteristics. Male house sparrows (Passer domesticus) possess a bib of black
      feathers, or badge, that is associated with behaviors important for reproduction
      including courtship behaviors, copulation, and aggression. Such behaviors are
      controlled by testosterone activity within the central nervous system and are
      strongly influenced by social status and female behavior. To understand how
      multiple factors interact to coordinate reproductive activity we explored
      relationships among social status, badge size, gonad volume, and the volumes of
      brain regions involved in male courtship and dominance (HVC, robust nucleus of
      the archistriatum, and the medial preoptic nucleus). A trend toward a U-shaped
      relationship was observed between dominance status and badge size, with the most
      dominant and most subordinate males possessing the largest badges. Male vocal
      expression, copulation, and aggression were positively related to dominance
      status, but not badge size. In contrast, the volumes of HVC, the medial preoptic
      nucleus and the gonads related positively to badge size, but not dominance.
      Females preferentially approached large-badged males regardless of dominance
      status, but this interest translated into copulation for dominant rather than
      subordinate males, a finding possibly related to the observation that dominant
      males vocalized at higher rates than subordinates. Subordinate males that had
      large badges, attracted female interest, and possessed the neuroendocrine
      potential to perform courtship behaviors might have been prevented from doing so
      through social interactions with dominant males within the flock.

PMID- 14726624
TI  - Oxytocin and vasopressin immunoreactivity within the forebrain and limbic-related
      areas in the mustached bat, Pteronotus parnellii.
AB  - The nonapeptides, oxytocin and arginine vasopressin, play an important role in
      mammalian social and reproductive behavior. Using immunocytochemical procedures,
      we identified oxytocin-immunoreactive neurons in the frontal and auditory
      cortices, limbic areas such as the medial septal nucleus, horizontal limb of the
      diagonal band and the amygdala. Only arginine vasopressin neurons were present in
      the bed nucleus of the stria terminalis. In limbic-related areas, the
      hypothalamic paraventricular and supraoptic nuclei and the nucleus centralis
      contained both oxytocin and arginine vasopressin neurons. The medial preoptic
      area showed a positive reaction for several arginine vasopressin fibers, but not
      oxytocin fibers, except in one female bat sacrificed during the breeding season.
      Arginine vasopressin fibers were observed in another limbic-related area, the
      periaqueductal gray. Furthermore, oxytocin was predominantly localized within
      sensory (e.g., auditory) and frontal cortex and limbic areas, whereas arginine
      vasopressin was restricted largely to known audiovocal regions of the
      periaqueductal gray. Classical neurosecretory nuclei in the hypothalamus contain
      both peptides. Oxytocin-immunoreactive neurons were also found in other
      structures such as the olfactory bulb, olfactory tubercle, primary and secondary
      motor cortex, fronto-parietal cortex, piriform cortex and the nucleus of the
      internal capsule. Both oxytocin and arginine vasopressin immunoreactivity was
      present in the suprachiasmatic nucleus, median eminence, neural lobe of the
      hypophysis and the pineal gland. Together with previous studies, the presence of
      these peptides within auditory areas of the cortex (sensory and frontal), and
      limbic as well as limbic-related regions provides anatomical evidence supporting
      their proposed role in social vocal behaviors and probably in auditory
      processing.

PMID- 14726625
TI  - Bigger brains or bigger nuclei? Regulating the size of auditory structures in
      birds.
AB  - Increases in the size of the neuronal structures that mediate specific behaviors
      are believed to be related to enhanced computational performance. It is not
      clear, however, what developmental and evolutionary mechanisms mediate these
      changes, nor whether an increase in the size of a given neuronal population is a
      general mechanism to achieve enhanced computational ability. We addressed the
      issue of size by analyzing the variation in the relative number of cells of
      auditory structures in auditory specialists and generalists. We show that bird
      species with different auditory specializations exhibit variation in the relative
      size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist,
      the hindbrain auditory nuclei involved in the computation of sound location show
      hyperplasia. This hyperplasia was also found in songbirds, but not in non
      auditory specialists. The hyperplasia of auditory nuclei was also not seen in
      birds with large body weight suggesting that the total number of cells is
      selected for in auditory specialists. In barn owls, differences observed in the
      relative size of the auditory nuclei might be attributed to modifications in
      neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory
      computation accompanies auditory specialization in different orders of birds.

PMID- 14726626
TI  - Efficacy of prednisolone and mizoribine therapy for diffuse IgA nephropathy.
AB  - OBJECTIVE: There have been only a few studies concerning oral prednisolone and
      mizoribine therapy for diffuse IgA nephritis (IgAN). We evaluated the efficacy of
      prednisolone and mizoribine therapy for diffuse IgAN. METHODS: We enrolled 34
      patients who had been diagnosed as having diffuse IgAN with severe proteinuria
      during the period from 1992 to 1999. Following diagnostic renal biopsy, the
      patients were treated with prednisolone, mizoribine, warfarin and dilazep
      dihydrochloride. The clinical features, laboratory data and pathological findings
      between pre- and post-therapy were investigated. RESULTS: The mean urinary
      protein excretion after 6 months of treatment had decreased significantly
      compared to pre-therapy. The incidence of hematuria in post-therapy was lower
      than that of pre-therapy. The grading index decreased significantly from 4.8 +/-
      2.1 at the first biopsy to 2.3 +/- 1.7 at the second biopsy (p < 0.001) and the
      staging index decreased significantly from 4.1 +/- 1.9 at the first biopsy to 2.7
      +/- 2.4 at the second biopsy (p < 0.05). Macrophage infiltration and alpha-smooth
      muscle actin-positive cells in the glomerulus and interstitial region decreased
      significantly in post-therapy compared with pre-therapy. At the most recent
      follow-up, none of the 34 patients had renal insufficiency. CONCLUSIONS: Our
      study suggested that prednisolone and mizoribine therapy is effective for those
      patients with the risk of progression of IgAN.

PMID- 14726627
TI  - Oxidative stress - a link between endothelial injury, coagulation activation, and
      atherosclerosis in haemodialysis patients.
AB  - BACKGROUND/AIM: Recently emerging evidence suggests that oxidative stress (SOX)
      may participate in atherogenesis. The aim of the present study was to establish
      whether enhanced SOX, involving endothelial injury, activation of coagulation,
      and inflammatory reaction, could be implicated in atherosclerotic diseases in
      haemodialysis (HD) patients. METHODS: Markers of SOX, endothelial injury,
      coagulation, and cytokines, were measured in the plasma of HD patients with and
      without cardiovascular disease (CVD), and of healthy controls by ELISA methods.
      Remodeling of the carotid arteries was assessed by measuring the intima-media
      thickness (IMT) as a surrogate of atherosclerotic disease in all groups. RESULTS:
      Markers of SOX, endothelial injury, and extrinsic coagulation pathway activation
      and IMT values were significantly elevated in HD patients, especially in those
      with CVD when compared with the control group. The von Willebrand factor antigen
      (vWF:Ag) levels were more increased in the patients with CVD than in those
      without. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte
      chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were
      significantly higher only in the HD group with CVD when compared with the
      controls. The IMT was strongly and directly correlated with Cu/Zn superoxide
      dismutase. Both IMT and Cu/Zn superoxide dismutase were positively correlated
      with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor,
      prothrombin fragment F1 + 2, monocte chemo-attractant protein 1, macrophage
      inflammatory protein 1 beta, and tumour necrosis factor alpha levels.
      Multivariate analysis identified vWF:Ag as the only independent variable
      significantly associated with an increased IMT. CONCLUSIONS: The present study
      suggests that enhanced SOX, involved pro-atherogenic cytokine and chemokines
      levels, endothelial injury, and coagulation activation may constitute a pathway
      for accelerated atherosclerosis in HD patients. The significant, independent
      association between IMT and vWF:Ag should be assessed in future studies to
      determine whether vWF:Ag elevation is causative or a by-product of the increased
      IMT.

PMID- 14726628
TI  - Rate-limiting steps in the development of atherosclerosis: the response-to-influx
      theory.
AB  - A large number of processes are involved in the pathogenesis of atherosclerosis
      but it is unclear which of them play a rate-limiting role. One way of resolving
      this problem is to investigate the highly non-uniform distribution of disease
      within the arterial system; critical steps in lesion development should be
      revealed by identifying arterial properties that differ between susceptible and
      protected sites. Although the localisation of atherosclerotic lesions has been
      investigated intensively over much of the 20th century, this review argues that
      the factor determining the distribution of human disease has only recently been
      identified. Recognition that the distribution changes with age has, for the first
      time, allowed it to be explained by variation in transport properties of the
      arterial wall; hitherto, this view could only be applied to experimental
      atherosclerosis in animals. The newly discovered transport variations which
      appear to play a critical role in the development of adult disease have
      underlying mechanisms that differ from those elucidated for the transport
      variations relevant to experimental atherosclerosis: they depend on endogenous NO
      synthesis and on blood flow. Manipulation of transport properties might have
      therapeutic potential.

PMID- 14726629
TI  - Changes in vascular distensibility during angiotensin-converting enzyme
      inhibition involve bradykinin type 2 receptors.
AB  - Changes in arterial stiffness and structure occur during cardiovascular diseases
      and can be modified by angiotensin-converting enzyme (ACE) inhibitors. In the
      present study we investigated the role of membrane-bound ACE (t-ACE) in the
      regulation of arterial structure and mechanics. Large and small arteries of t-ACE
      /- mice were isolated to determine the passive pressure-diameter relationship. We
      observed that t-ACE-/- mice exhibit a reduced arterial distensibility compared to
      t-ACE+/+ mice. This reduced arterial distensibility was also observed after 9
      weeks of captopril treatment (80 mg/kg/ day). We hypothesized that bradykinin
      type 2 receptor (BK(2)) stimulation might be involved in the regulation of
      arterial stiffness. t-ACE-/- and t-ACE+/+ mice were treated with Hoe 140 (1
      mg/kg/day) for 14 days. After Hoe 140 treatment, both the structural and
      mechanical changes observed in the t-ACE-/- carotid artery were abolished.
      Although Hoe 140 administration increased blood pressure in both groups by
      approximately 10 mm Hg, the pressure difference between the two groups did not
      change. Thus, t-ACE is involved in the regulation of arterial distensibility. The
      changes observed in t-ACE-/- mice are not caused by an altered fetal development.
      Moreover, it is likely that the regulation of arterial distensibility by ACE
      involves stimulation of the BK(2) receptor.

PMID- 14726630
TI  - ICAM-3 activation modulates cell-cell contacts of human bone marrow endothelial
      cells.
AB  - The Ig-like cell adhesion molecule ICAM-3 is mainly expressed on human leukocytes
      and is involved in cell-cell interactions. Its expression on endothelium is
      observed during disorders such as Crohn's disease and in solid tumors. We found
      low but detectable expression of ICAM-3 on VE-cadherin-expressing cells from
      primary human bone marrow aspirates, i.e. endothelial cells, and on primary human
      endothelial cells from cord blood. Also, immortalized human umbilical cord
      endothelial cells and human bone marrow endothelial cells showed ICAM-3
      expression. However, its function on human endothelium is not known.
      Surprisingly, activation of endothelial ICAM-3 by crosslinking with specific
      antibodies resulted in a drop in the electrical resistance of bone marrow
      endothelial monolayers. In line with this, immunocytochemical analysis showed a
      loss of endothelial cell-cell contacts after ICAM-3 crosslinking in HBMEC.
      Detailed biochemical analysis showed an association of moesin and in a later
      stage ezrin with ICAM-3 upon crosslinking in HBMEC. Moreover, ICAM-3 crosslinking
      induced the production of reactive oxygen species (ROS), which are known to be
      involved in the control of endothelial cell-cell contacts. In conclusion, we
      showed that ICAM-3 is expressed on human bone marrow endothelial cells and
      controls endothelial integrity via ROS-dependent signaling.

PMID- 14726631
TI  - Insulin-stimulated myocardial glucose uptake and the relation to perfusion and
      the nitric oxide system.
AB  - In skeletal muscle, insulin increases glucose uptake through endothelium-derived
      nitric oxide (EDNO)-dependent vasodilation. Insulin also enhances myocardial
      glucose uptake, but it is unknown whether vasodilation participates in the
      underlying mechanism. We studied whether insulin-stimulated myocardial glucose
      uptake (MGU) is associated with perfusion changes and whether MGU is EDNO
      dependent. Myocardial perfusion (MBF) and MGU were measured three times with
      positron emission tomography in 8 healthy volunteers (56 +/- 6 years): (1).
      During a hyperinsulinemic euglycemic clamp (clamp), (2). during clamp and
      blockage of the nitric oxide synthesis by L-NMMA and (3). during clamp and nitric
      oxide stimulation with nitroglycerin. We measured MBF at rest before and during
      clamp utilizing (13)N-ammonia and (18)F-fluoro-deoxy-glucose as perfusion and
      glucose tracers, respectively. Hemodynamics were affected neither by insulin nor
      by L-NMMA. Nitroglycerin reduced rate-pressure product. Insulin did not affect
      MBF. L-NMMA reduced MBF (0.60 +/- 0.15 vs. 0.66 +/- 0.14 ml/g/min; p < 0.05),
      while MGU was unchanged. Nitroglycerin did not alter MBF, while MGU was reduced
      (0.44 +/- 0.11 vs. 0.52 +/- 0.13 micromol/g/min; p = 0.05). Insulin-stimulated
      MGU does not rely on a simultaneous increment of MBF. Myocardial glucose uptake
      can be stimulated even when MBF decreases, suggesting that autoregulation of MGU
      is preserved despite uncoupling of vascular autoregulation.

PMID- 14726632
TI  - Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced
      dermatitis by local action in NC/Nga mice.
AB  - BACKGROUND: FK506 ointment (tacrolimus ointment, protopic) is a new drug
      therapeutically effective for patients with atopic dermatitis (AD). However, the
      mechanism of action of FK506 ointment on AD is not fully understood. METHODS: We
      examined the effect of FK506 ointment on mite antigen-induced dermatitis in
      NC/Nga mice. Clinical symptoms and ear thickness were recorded, and
      histopathological studies and in vitro analyses were performed. RESULTS: Topical
      application of FK506 ointment (0.03-0.3%) suppressed the development of
      dermatitis. In the lesional skin, both interleukin (IL)-4 and interferon (IFN)
      gamma were detected, even though the IL-4+/IFN-gamma- T helper 2 (Th2) population
      was predominant in the regional lymph nodes (LNs). Topical application of FK506
      treatment reduced the elevated level of both IL-4 and IFN-gamma in the skin, but
      did not decrease the expansion of the Th2 population in the LNs. CONCLUSIONS:
      Topical application of FK506 ointment suppresses dermatitis by inhibiting the
      activation of inflammatory cells locally, without systemic immune suppression, in
      this AD model.

PMID- 14726633
TI  - Secondary lymphoid tissue chemokine (CCL21) is upregulated in allergic contact
      dermatitis.
AB  - Chemokines are important players in the development of allergic contact
      dermatitis (ACD). The participation of secondary lymphoid tissue chemokine
      (CCL21) is essential in the induction of the disease due to its expression in
      lymphatic vessels and in secondary lymphoid organs. Since there is no information
      about its participation during the effector phase of ACD, we studied this
      chemokine in patients already diagnosed with ACD, who were challenged with the
      relevant positive and negative (control) antigens. All patients showed a specific
      antigen-induced immune response characterized by early expression of inflammatory
      markers in blood endothelial cells followed by dermal accumulation of mononuclear
      cells with an important increase in infiltration of CXCR3+ but not of CCR7+
      cells. In situ hybridization and immunohistochemistry showed low levels of CCL21
      in lymphatic vessels at 2 h, whereas they were significantly increased at 10 and
      48 h in all positive patch tests. In contrast, very low expression of this
      chemokine was observed in skin biopsies from the control site at 48 h. In
      addition, Langerin+ cells, which were present in dermis from positive patch tests
      at 2 h, were diminished in number at 10 and 48 h, but a significant number of
      those cells was still present in dermal areas of the control site at 48 h. We
      demonstrate for the first time that CCL21, a constitutively expressed chemokine,
      is strongly upregulated in human lymphatic vessels during a Th1/Tc1 allergic
      inflammatory response. This can provide the signal required for CCR7+ cells to
      leave the skin through CCL21-positive lymphatic vessels.

PMID- 14726634
TI  - B lymphocyte selection and survival in systemic lupus.
AB  - B lymphocytes are an essential element in the body's immune system. Engagement of
      the B cell receptor is responsible for initiating the signaling events that can
      activate, inactivate or physically eliminate B cells, depending on the magnitude
      and duration of the signal. Control of B cell signaling occurs through both
      positive and negative regulation, as well as through the actions of molecular
      scaffolds that contribute to the formation of signaling complexes. Inactivation
      of genes encoding signaling molecules was shown to result in clinical
      manifestations reminiscent of systemic autoimmunity in experimental animals.
      Aberrant expression of some signaling molecules was also observed in patients
      with systemic autoimmune diseases. Understanding the mechanisms that subvert B
      cell receptor transduction pathways is likely to aid in the development of
      therapeutic agents to treat autoimmune diseases.

PMID- 14726635
TI  - Do mouse models of allergic asthma mimic clinical disease?
AB  - Experimental mouse models of allergic asthma established almost 10 years ago
      offered new opportunities to study disease pathogenesis and to develop new
      therapeutics. These models focused on the factors governing the allergic immune
      response, on modeling clinical behavior of allergic asthma, and led to insights
      into pulmonary pathophysiology. Although mouse models rarely completely reproduce
      all the features of human disease, after sensitization and respiratory tract
      challenges with antigen, wild-type mice develop a clinical syndrome that closely
      resembles allergic asthma, characterized by eosinophilic lung inflammation,
      airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and
      eventually, airway remodeling. There are, however, differences between mouse and
      human physiology that threaten to limit the value of mouse models. Three examples
      of such differences relate to both clinical manifestations of disease and
      underlying pathogenesis. First, in contrast to patients who have increased
      methacholine-induced AHR even when they are symptom-free, mice exhibit only
      transient methacholine-induced AHR following allergen exposure. Second, chronic
      allergen exposure in patients leads to chronic allergic asthma, whereas repeated
      exposures in sensitized mice causes suppression of disease. Third, IgE and mast
      cells, in humans, mediate early- and late-phase allergic responses, though both
      are unnecessary for the generation of allergic asthma in mice. Taken together,
      these observations suggest that mouse models of allergic asthma are not exact
      replicas of human disease and thus, question the validity of these models.
      However, observations from mouse models of allergic asthma support many existing
      paradigms, although some novel discoveries in mice have yet to be verified in
      patients. This review presents an overview of the clinical aspects of disease in
      mouse models of allergic asthma emphasizing (1). the factors influencing the
      pathophysiological responses during the initiation and perpetuation of disease,
      (2). the utility of mouse models for studying clinical manifestations of disease,
      and (3). the applicability of mouse models for testing new treatments for
      allergic asthma.

PMID- 14726636
TI  - Targeted molecular imaging.
AB  - Molecular imaging aims to visualize the cellular and molecular processes
      occurring in living tissues, and for the imaging of specific molecules in vivo,
      the development of reporter probes and dedicated imaging equipment is most
      important. Reporter genes can be used to monitor the delivery and magnitude of
      therapeutic gene transfer, and the time variation involved. Imaging technologies
      such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are
      able to non-invasively detect, measure, and report the simultaneous expression of
      multiple meaningful genes. It is believed that recent advances in reporter
      probes, imaging technologies and gene transfer strategies will enhance the
      effectiveness of gene therapy trials.

PMID- 14726637
TI  - Automated lung nodule detection at low-dose CT: preliminary experience.
AB  - OBJECTIVE: To determine the usefulness of a computer-aided diagnosis (CAD) system
      for the automated detection of lung nodules at low-dose CT. MATERIALS AND
      METHODS: A CAD system developed for detecting lung nodules was used to process
      the data provided by 50 consecutive low-dose CT scans. The results of an initial
      report, a second look review by two chest radiologists, and those obtained by the
      CAD system were compared, and by reviewing all of these, a gold standard was
      established. RESULTS: By applying the gold standard, a total of 52 nodules were
      identified (26 with a diameter < or = 5 mm; 26 with a diameter >5 mm). Compared
      to an initial report, four additional nodules were detected by the CAD system.
      Three of these, identified only at CAD, formed part of the data used to derive
      the gold standard. For the detection of nodules >5 mm in diameter, sensitivity
      was 77% for the initial report, 88% for the second look review, and 65% for the
      CAD system. There were 8.0+/-5.2 false-positive CAD results per CT study.
      CONCLUSION: These preliminary results indicate that a CAD system may improve the
      detection of pulmonary nodules at low-dose CT.

PMID- 14726638
TI  - Stereotactic core-needle biopsy of non-mass calcifications: outcome and accuracy
      at long-term follow-up.
AB  - OBJECTIVE: To determine, by means of long-term follow-up evaluation, the outcome
      and accuracy of stereotactic core-needle biopsy (SCNB) of non-mass calcifications
      observed at mammography, and to analyze the factors contributing to false
      negative findings. MATERIALS AND METHODS: Using a 14-gauge needle, SCNB was
      performed in cases involving 271 non-mass calcified lesions observed at
      mammography in 267 patients aged 23 72 (mean, 47) years. We compared the SCNB
      results with those of long-term follow-up which included surgery, mammography
      performed for at least six months, and reference to Korean Cancer Registry
      listings. We investigated the retrieval rate for calcifications observed at
      specimen mammography and histologic evaluation, and determined the incidence rate
      of cancer, sensitivity, and the underestimation rate for SCNB. False-negative
      cases were evaluated in terms of their mammographic findings, the effect of the
      operators' experience, and the retrieval rate for calcifications. RESULTS: For
      specimen mammography and histologic evaluation of SCNB, the retrieval rate for
      calcifications was, respectively, 84% and 77%. At SCNB, 54 of 271 lesions (19.9%)
      were malignant [carcinoma in situ, 45/54 (83%)], 16 were borderline, and 201 were
      benign. SCNB showed that the incidence of cancer was 5.0% (6/120) in the benign
      mammographic category and 31.8% (48/151) in the malignant category. The findings
      revealed by immediate surgery and by longterm follow-up showed, respectively,
      that the sensitivity of SCNB was 90% and 82%. For borderline lesions, the
      underestimation rate was 10%. For false-negative cases, which were more frequent
      among the first ten cases we studied (p = 0.01), the most frequent mammographic
      finding was clustered amorphous calcifications. For true-negative and false
      negative cases, the retrieval rate for calcifications was similar at specimen
      mammography (83% and 67%, respectively; p = 0.14) and histologic evaluation (79%
      and 75%, respectively; p = 0.47). CONCLUSION: In this study group, most diagnosed
      cancers were in-situ lesions, and long-term follow-up showed that the sensitivity
      of SCNB was 82%. False-negative findings were frequent during the operators'
      learning period.

PMID- 14726640
TI  - Correlation of patient weight and cross-sectional dimensions with subjective
      image quality at standard dose abdominal CT.
AB  - OBJECTIVE: We evaluated the association between patients' weight and abdominal
      cross-sectional dimensions and CT image quality. MATERIALS AND METHODS: We
      prospectively evaluated 39 cancer patients aged more than 65 years with
      multislice CT scan of abdomen. All patients underwent equilibrium phase contrast
      enhanced abdominal CT with 4 slices (from top of the right kidney) obtained at
      standard tube current (240-280 mA). All other scanning parameters were held
      constant. Patients' weight was measured just prior to the study. Cross-sectional
      abdominal dimensions such as circumference, area, average anterior abdominal wall
      fat thickness and, anteroposterior and transverse diameters were measured in all
      patients. Two subspecialty radiologists reviewed randomized images for overall
      image quality of abdominal structures using 5- point scale. Non-parametric
      correlation analysis was performed to determine the association of image quality
      with patients' weight and cross-sectional abdominal dimensions. RESULTS: A
      statistically significant negative linear correlation of 0.46, 0.47, 0.47, 0.58,
      0.56, 0.54, and 0.56 between patient weight, anterior abdominal fat thickness,
      anteroposterior and transverse diameter, circumference, cross-sectional area and
      image quality at standard scanning parameters was found (p<0.01). CONCLUSION:
      There is a significant association between image quality, patients' weight and
      cross-sectional abdominal dimensions. Maximum transverse diameter of the abdomen
      has the strongest association with subjective image quality.

PMID- 14726639
TI  - Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic
      US using a microbubble contrast agent.
AB  - OBJECTIVE: To analyze the contrast-enhancement patterns obtained at pulse
      inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine
      tumor vascularity and the acoustic emission effect. MATERIALS AND METHODS: We
      reviewed pulse-inversion images in 90 consecutive patients with focal hepatic
      lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and
      hemangioma (n=17). Vascular and delayed phase images were obtained immediately
      and five minutes following the injection of a microbubble contrast agent. Tumoral
      vascularity at vascular phase imaging and the acoustic emission effect at delayed
      phase imaging were each classified as one of four patterns. RESULTS: Vascular
      phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of
      metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed
      phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic,
      decreased enhancement in 93% of metastases; and hypoechoic and reversed
      echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement
      patterns were associated with a specificity of 91% or greater, and 92% or
      greater, respectively, and with positive predictive values of 71% or greater, and
      85% or greater, respectively. CONCLUSION: Contrast-enhancement patterns depicting
      tumoral vascularity and the acoustic emission effect at PIHI can help
      differentiate focal hepatic lesions.

PMID- 14726641
TI  - Ablation of symptomatic cysts using absolute ethanol in 11 patients with
      autosomal-dominant polycystic kidney disease.
AB  - OBJECTIVE: To evaluate the effects of cyst ablation with absolute ethanol in
      autosomal-dominant polycystic kidney disease (ADPKD) patients with symptomatic
      cysts. MATERIALS AND METHODS: Using absolute ethanol, cyst ablation was performed
      in 11 patients with documented ADPKD who suffered cyst pain refractory to medical
      treatment. An ethanol solution was instilled into the largest symptomatic cysts
      through a catheter. We assessed the therapeutic efficacy of the procedure by
      tracking subjective pain relief during a 3 to 24-month follow-up period after
      ablation. RESULTS: At follow-up, we found that the duration of subjective pain
      relief was 12 to 24 months in seven patients, 4 to 11 months in one, and less
      than 3 months in three. CONCLUSION: Selective ablation of a symptomatic cyst may
      be a valid option in managing chronic pain caused by one or a few large cysts in
      ADPKD patients.

PMID- 14726642
TI  - Prenatal sonographic diagnosis of focal musculoskeletal anomalies.
AB  - Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or
      be accompanied by numerous other conditions such as genetic disorders, karyotype
      abnormalities, central nervous system anomalies and other skeletal anomalies.
      Isolated focal musculoskeletal anomaly does, however, also occur; its early
      prenatal diagnosis is important in deciding prenatal care, and also helps in
      counseling parents about the postnatal effects of numerous possible associated
      anomalies. We have encountered 50 cases involving focal musculoskeletal
      anomalies, including focal limb dysplasia [radial ray abnormality (n=3),
      mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly
      (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of
      the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1),
      curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine
      [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five
      [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2)] were confirmed by
      postnatal physical evaluation, two (focal spine anomalies) were diagnosed after
      postnatal radiologic examination, and the remaining 43 were proven at autopsy.
      For each condition, we describe the prenatal sonographic findings, and include a
      brief review.

PMID- 14726643
TI  - Primary calcified T-cell lymphoma of the urinary bladder: a case report.
AB  - Primary malignant lymphoma of the urinary bladder is extremely rare, and to our
      knowledge, no case described in the radiologic literature has been accompanied by
      calcification. We report a case in which the condition was associated with
      calcification, and describe the pelvic CT and MR imaging findings.

PMID- 14726644
TI  - Carcinosarcoma of the renal pelvis and urinary bladder: a case report.
AB  - Carcinosarcomas are rare biphasic malignant neoplasms with an epithelial and a
      spindle cell component. We present a 62-year-old man with a history of noticeably
      abdominal distension, proved by surgery to be caused by carcinosarcoma of the
      renal pelvis and urinary bladder, occupying the entire left abdominal flank. We
      also illustrate the appearance of this rare entity on sonography and computed
      tomography.

PMID- 14726645
TI  - Prenatal sonographic and MR imaging findings of extensive fetal lymphangioma: a
      case report.
AB  - We report the imaging findings in a case of fetal lymphangioma involving the
      retroperitoneum and right lower extremity, and diagnosed by ultrasonography and
      magnetic resonance (MR) imaging at 26 weeks of gestation. Prenatal ultrasonograms
      and T2-weighted single-shot fast spin-echo MR images clearly revealed an
      extensive, multilocular cystic mass with internal hemorrhage in the
      retroperitoneum extending to the lower extremity.

PMID- 14726646
TI  - Arsenic trioxide and paclitaxel induce apoptosis by different mechanisms.
AB  - Arsenic trioxide (ATO) and paclitaxel (TAXOL) are effective in the treatment of
      various types of cancers. Both drugs induce G2/M arrest. We have previously shown
      that ATO is a potent inducer of apoptosis in myeloma cells expressing mutant p53
      engaging both the intrinsic and extrinsic apoptotic pathways. Here we compared
      the effect of ATO and TAXOL on myeloma cells expressing mutant p53 and varying
      levels of Bcl-2. ATO rapidly induced Apo2/TRAIL, activation of caspase 8,
      cleavage of BID, depolarization of mitochondrial membrane (MM) and release of AIF
      from mitochondria in a Bcl-2 independent fashion. Apoptosis was associated with
      early formation of ring-like perinuclear condensed chromatin colocalized with
      AIF. In contrast, paclitaxel-induced apoptosis MM depolarization, cytochrome C
      release and activation of caspase 9 were all blocked by Bcl-2. Apoptosis was
      associated with a random chromatin condensation and nuclear fragmentation with no
      early involvement of AIF.

PMID- 14726647
TI  - Human diploid fibroblasts are refractory to oncogene-mediated transformation.
AB  - It has long been known that human cells are more refractory than rodent cells
      against oncogenic transformation in vitro. Recent success to make normal human
      cells susceptible to oncogene-mediated transformation by the ectopic expression
      of the telomerase catalytic subunit (hTERT) introduces the possibility that the
      difference in the regulation of telomerase expression can explain the different
      susceptibility to transformation between human and rodent cells. In a recent
      study, however, we demonstrated that normal human fibroblasts are still more
      resistant than normal rodent fibroblasts to oncogenic transformation even with
      the ectopic expression of hTERT. Our results clearly indicate that a difference
      in telomere biology can not fully account for the species difference in
      transformability, and that normal human cells have still undefined intrinsic
      mechanisms rendering them resistant to oncogenic transformation.

PMID- 14726648
TI  - Receptor tyrosine kinase signaling and primordial germ cell development.
AB  - Primordial germ cells (PGCs) give rise to sperms and eggs. Their development is
      crucial to species propagation and has to be precisely controlled. Studies in
      several model organisms have identified many genes involved in the specification
      and guided migration of PGCs. However, the mechanisms governing the behaviors of
      these unique cells remain to be investigated. Interestingly, PGCs share certain
      cellular properties with metastasizing cancer cells including proliferation,
      invasion of other tissues, survival and migration. Recently we have shown that in
      Drosophila the receptor tyrosine kinase Torso activates both STAT and Ras during
      the early phase of PGC development. In later stages, activation of both STAT and
      Ras, likely by other molecules, is required continuously for PGC migration. The
      requirement for RTK suggests molecular conservation between flies and mice in PGC
      development and also suggests that germ cells and cancer cells share certain
      intracellular signaling strategies.

PMID- 14726649
TI  - Mitotic functions of the Ran GTPase network: the importance of being in the right
      place at the right time.
AB  - The Ran GTPase has important roles in nucleocytoplasmic transport, cell cycle
      progression, nuclear organization and nuclear envelope (NE) assembly. In this
      review, we discuss emerging evidence that implicate the Ran GTPase system in
      mitotic control in mammalian cells. Recent work indicates that members of the Ran
      network control two fundamental aspects of the mammalian mitotic apparatus: (i)
      centrosome and spindle pole function, and (ii) kinetochore function. It is also
      emerging that, after NE breakdown, specific Ran network components assemble in
      local combinations at crucial sites of the mitotic apparatus. In the light of
      these findings, the original notion that nucleotide-bound forms of the Ran GTPase
      are distributed along a unique "gradient" in mitotic cells should be re-examined.
      Available data also suggest that the Ran system is deregulated in certain
      cellular contexts: this may represent a favoring condition for the onset and
      propagation of mitotic errors that can predispose cells to become genetically
      unstable and facilitate neoplastic growth.

PMID- 14726650
TI  - A non-adaptationist perspective on evolution of genomic complexity or the
      continued dethroning of man.
AB  - A new, non-adaptationist theory of evolution of genomic complexity was recently
      proposed by Lynch and Conery. This concept holds that increase in complexity seen
      in eukaryotic genomes is a 'syndrome' caused by increase in genome entropy, which
      is inevitably triggered by reduction of population size. Here, I discuss the
      definitions of genomic entropy and complexity and the evidence supporting the
      entropic theory of genome complexity evolution, including new observations on
      concordant gain and loss of genes and introns in eukaryotic genomes. I further
      consider the far-reaching biological and philosophical implications of this
      theory.

PMID- 14726651
TI  - BRCA2-RAD51-DSS1 interplay examined from a microbial perspective.
AB  - The tumor suppressor BRCA2 plays an essential role in the repair of double-strand
      DNA breaks by regulating the action of the RAD51 recombinase. The activity of
      BRCA2 is in turn governed by DSS1, a small acidic protein that appears to
      function as a necessary cofactor. A model fungal system that reproduces the BRCA2
      RAD51 interaction offers the opportunity to understand the mechanism of DSS1
      activation at the molecular level.

PMID- 14726652
TI  - Genetic dissection of mammalian Cdc7 kinase: cell cycle and developmental roles.
AB  - Cdc7, originally discovered by Hartwell as a budding yeast mutant that arrests
      immediately before the onset of S phase, is conserved through evolution and plays
      essential roles in initiation of mitotic DNA replication. Inducible inactivation
      of Cdc7 in mouse embryonic stem cells leads to rapid cessation of DNA synthesis
      and the subsequent activation of checkpoint responses, resulting in p53
      activation and eventually p53-mediated apoptosis. This indicates a requirement of
      Cdc7 kinase for ongoing replication of mammalian genomes, and loss of Cdc7 kinase
      presumably generates arrested replication fork signals. Cdc7-/- mice or embryonic
      fibroblast cells (MEFs) expressing a low level of transgene-encoded Cdc7 protein
      are viable but exhibit reduced body size with impaired germ cell development and
      decreased cell proliferation. Interestingly, these phenotypes are largely
      corrected by the presence of an additional copy of the transgene, resulting in
      increased level of Cdc7 expression. This indicates the requirement of a critical
      level of Cdc7 for normal cell proliferation and development of specific organs.
      These results from mammals will be discussed in conjunction with the pleiotropic
      effects of Cdc7 mutation observed in yeasts.

PMID- 14726653
TI  - Differential effects of selective COX-2 inhibitors on cell cycle regulation and
      proliferation of glioblastoma cell lines.
AB  - It is well established that traditional NSAIDs, which inhibit cyclooxygenase
      (COX) 1 and COX-2, have the potential to reduce the risk of colorectal cancer.
      New generation COX inhibitors have been developed that selectively inhibit COX-2,
      which might cause less side effects while still retaining their therapeutic
      potential. As patients with brain tumors, such as glioblastoma, exhibit a very
      poor prognosis, we began to explore whether COX inhibitors could be useful for
      the treatment of this type of tumor. We found that celecoxib inhibited the
      proliferation of various glioblastoma cell lines in vitro much more potently than
      traditional NSAIDs. In addition, although several different selective COX-2
      inhibitors potently reduced PGE2 levels in these cells, none of them exerted anti
      proliferative effects that were comparable to celecoxib. The addition of external
      PGE2 to celecoxib-treated cells did not restore proliferation, indicating that
      growth inhibition by celecoxib was not mediated via the blockage of PGE2
      production. In an effort to determine the underlying molecular processes that
      might mediate celecoxib's potent anti-proliferative effects, we found a loss of
      the activity of cyclin-dependent kinases, the essential regulators of cell
      proliferation, which was due to the transcriptional downregulation of cyclin A
      and cyclin B expression. Taken together, our results show that celecoxib exerts
      COX-2-independent anti-proliferative effects on glioblastoma cell growth, which
      are more potent than those of other selective COX-2 inhibitors or traditional
      NSAIDs, and which are mediated via the transcriptional inhibition of two
      essential components of the cell cycle machinery, cyclin A and cyclin B.

PMID- 14726654
TI  - Progress in the development of nucleic acid therapeutics for cancer.
AB  - Many cancers are characterized by abnormal gene expression. Silencing these
      aberrantly expressed genes could therefore have therapeutic utility and by virtue
      of specific targeting, prove less toxic than conventional cancer therapies. A
      number of strategies for inhibiting gene expression have been developed. Some,
      such as triple helix forming, or decoy transcription factor binding,
      oligodeoxynucleotides seek to disrupt gene expression at the level of
      transcription. Others, such as antisense oligonucleotides (ODN) and short
      interfering RNA (siRNA) molecules attempt to disrupt expression at the level of
      mRNA translation. In this review, we provide an overview of gene silencing agents
      and their development for use as cancer therapeutics. We will focus on mRNA
      targeting methodologies and discuss issues core to the clinical success of these
      molecules including cellular delivery, and successful targeting. The potential
      utility of nucleic acid based therapeutics in the clinic will also be addressed.

PMID- 14726655
TI  - Methylation status of RB1 promoter in Indian retinoblastoma patients.
AB  - Retinoblastoma can arise due to mutational inactivation or methylation of RB1
      gene promoter. A 600-bp CpG island consisting of the essential promoter is
      present at the 5' end of RB1 gene. Hypermethylation of the CpG island within the
      RB1 promoter region has been described in unilateral retinoblastoma. In vitro and
      in vivo studies have suggested that methylation of the RB1 promoter dramatically
      reduces gene activity. In the present study methylation status of the CpG island
      within the promoter region of RB1 gene has been evaluated by methylation specific
      polymerase chain reaction to define the molecular mechanism responsible for
      retinoblastoma in Indian patients. One unilateral and two bilateral nonhereditary
      patients had methylation of the RB1 promoter region in which 6.6% of our patients
      had complete methylation of the RB1 promoter region. This study shows methylation
      of RB1 promoter is not a major mechanism for retinoblastoma patients in India.
      Methylation analysis is used in genetic counseling of the family.

PMID- 14726656
TI  - Overexpression of E2F-1 in lung and liver metastases of human colon cancer is
      associated with gene amplification.
AB  - We have shown previously that metastatic tumors of human colorectal cancer in
      lung as compared to liver have high levels of thymidylate synthase (TS) mRNA
      expression that correlated with high levels of E2F-1 mRNA expression. We now
      report that Comparative Genomic Hybridization (CGH) and DNA PCR analyses of lung
      and liver metastases of human colon cancer show frequent gains in the region of
      chromosome 20q and have an increase in gene copy number of E2F-1. In as much as
      TS is transcriptionally regulated by E2F-1, these results provide an explanation
      for the high levels of TS mRNA noted in some tumor samples.

PMID- 14726657
TI  - Maintaining youth in Drosophila neural progenitors.
AB  - An important question is how dividing stem cells maintain competence to generate
      multiple cell types, whereas most other cells become progressively restricted
      during development. The molecular basis for progenitor competence--or how
      competence is progressively restricted--has remained mysterious. Recent work has
      shown that Drosophila neuroblasts and mammalian neural progenitors are more
      similar than previously appreciated, and provide an excellent model system for
      using Drosophila genetics to unravel the molecular nature of progenitor
      competence and how it becomes progressively restricted during development.

PMID- 14726658
TI  - Perp-etrating p53-dependent apoptosis.
AB  - The induction of apoptosis is a fundamental mechanism by which the p53
      transcriptional activator protein suppresses tumor development. Recently, the
      roles of several p53 target genes in mediating the p53 apoptotic response have
      been queried through loss-of-function analysis with knockout mouse models. These
      studies have demonstrated that the p53 targets Noxa, Puma, and Perp play cell
      type-specific roles in p53-mediated apoptosis. Perp, a tetraspan protein
      localizing to the plasma membrane, rather than to mitochondria, is a novel type
      of p53 effector that may stimulate apoptosis through a different mechanism from
      the BH3-containing proteins Noxa, Puma, and Bax.

PMID- 14726659
TI  - Telomerase is frequently activated in tumors with microsatellite instability.
AB  - Telomeres are specialized structures at the ends of eukaryotic chromosomes that
      are required for the complete replication and stability of naturally occurring
      chromosome ends. Telomere stabilization is critical for the unlimited cellular
      proliferation that is necessary for tumor formation. While most tumors achieve
      telomere stabilization through activation of telomerase, a subset of tumors
      utilize a recombination-based mechanism termed Alternative Lengthening of
      Telomeres (ALT) to maintain chromosome termini. Tumors utilizing ALT for telomere
      preservation will likely be refractory to treatment with telomerase inhibitors.
      Furthermore, tumors carrying mutations that predispose a cell to utilize ALT may
      activate this pathway when challenged by telomerase inhibition. Mutation of the
      mismatch repair (MMR) pathway enhances telomerase independent survival in yeast,
      with the survivors using recombination-based pathways for telomere maintenance.
      One possibility is that mutation of the MMR pathways alleviates suppression of
      recombination, thereby abrogating the need for telomerase activation. If true,
      one might predict an increased frequency of tumors harboring MMR mutation to use
      ALT for telomere maintenance. Here we characterized tumors with and without MMR
      mutation for the presence of telomerase activity versus ALT. We found similarly
      frequent activation of telomerase in tumors with and without MMR mutation,
      suggesting that human tumors with MMR mutation may respond favorably to treatment
      with telomerase inhibitors.

PMID- 14726660
TI  - Activating mutations in STAT3 and STAT5 differentially affect cellular
      proliferation and apoptotic resistance in multiple myeloma cells.
AB  - Multiple Myeloma (MM) is a progressive malignancy with poor prognosis, commonly
      treated by the use of the glucocorticoid Dexamethasone. Myeloma cells resist
      Dexamethasone induced apoptosis when exposed to IL-6 or IGF-1, both of which are
      known to activate several signaling cascades. For the first time, we show the
      actual contribution of downstream mediators, i.e., activated STAT factors,
      independent of the contribution of their upstream signaling pathways, on the
      proliferation and Dexamethasone rescue effects of IL-6 and IGF-1 in Multiple
      Myeloma. Retroviral transduction of cytokine dependent myeloma cells with
      activated STAT transcription factor constructs overcomes the cells dependence on
      cytokines for growth, allowing proliferation even in very low serum levels.
      However, the rescue of these previously cytokine dependent cells with activated
      STATs does not result in an increase in resistance to Dexamethasone induced
      apoptosis. Despite the presence of activated STAT3 and STAT5a, apoptosis is
      induced upon exposure to micromolar levels of Dexamethasone, and IL-6 or IGF-1 is
      still required to rescue the cells. The ability of these factors to block
      apoptosis is abrogated by the addition of PI-3 Kinase specific inhibitors, but
      not inhibitors that target the MAP Kinase pathway. However, ectopic expression of
      activated STAT3 results in partial rescue from apoptosis of cells treated with
      FAS ligand. Our data suggests that mechanisms of resistance to induced apoptosis
      and cellular proliferation are separate and distinct in cytokine dependent
      myeloma cells.

PMID- 14726661
TI  - A phase II study of topotecan and cyclophosphamide with G-CSF in patients with
      advanced small cell lung cancer.
AB  - PURPOSE: We conducted a multicenter phase II study to evaluate the efficacy and
      safety of the combination of topotecan and cyclophosphamide for patients with
      advanced small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients were
      eligible if they had newly diagnosed extensive stage SCLC or if they had SCLC
      that progressed more than three months after completion of the first chemotherapy
      regimen. Patients were treated every 21 days with cyclophosphamide 600 mg/m2 IV
      on day 1 and topotecan 1.0 mg/m2 on days 1 to 5. Filgrastim was administered for
      10 days starting on day 6. Patients were evaluated for objective tumor response,
      time to tumor progression, overall survival and toxicity. RESULTS: Forty-two
      eligible patients were treated. Seventeen patients (40.5%) had an objective
      response including 4 (9.5%) complete remissions (CR). Fifteen patients (35.7%)
      had stable disease. There are 2 patients known to be alive at the time of this
      report: one with stable disease at 26 months and another with a CR at 37 months.
      The median number of cycles completed was 6 (range 1-12). The major toxicities
      were grades 3 and 4 neutropenia (73.8%), grades 3 and 4 anemia (35.7%) and grades
      3 and 4 thrombocytopenia (50%). Five patients died during the first cycle of
      chemotherapy. The median time to progression was 3 months (range 5 days-36
      months) (CI: 51-135 days) and the median overall survival was 9 months (5 days-37
      months) (CI: 210-330 days). The two-year survival rate was 21%. CONCLUSIONS: The
      combination of topotecan and cyclophosphamide is highly active in small cell lung
      cancer. Myelosuppression is the major toxicity and is rapidly reversible in most
      patients. The incidence of treatment-related mortality was comparable to some
      other intensive chemotherapy regimens. This incidence is unacceptably high and
      indicates better selection criteria are needed in order to exclude patients at
      excessive risk of morbidity.

PMID- 14726662
TI  - Development and cancer: lessons learned in the pancreas.
AB  - Cancer progression and organ development are similar phenomena. Both involve
      rapid bursts of proliferation, angiogenesis, tissue remodeling, and cell
      migration. Therefore, it is not surprising that both processes utilize similar
      signaling machinery. In fact, many recent studies have suggested that cancer is a
      disease triggered by the erroneous re-activation of signaling pathways that are
      typically downregulated after the completion of embryonic development. This link
      between embryonic development and cancer is particularly exciting because it
      suggests that we might be able to exploit the knowledge gained in studies of
      Developmental Biology to obtain novel insights into tumor biology. Our evolving
      understanding of pancreatic adenocarcinoma is an excellent example of this
      relationship between development and cancer. Here we discuss recent studies have
      indicated important roles for two major developmental signaling pathways in
      pancreatic cancer: Notch and Hedgehog (Hh).

PMID- 14726663
TI  - The Tyr-kinase inhibitor AG879, that blocks the ETK-PAK1 interaction, suppresses
      the RAS-induced PAK1 activation and malignant transformation.
AB  - AG 879 has been widely used as a Tyr kinase inhibitor specific for ErbB2 and FLK
      1, a VEGF receptor. The IC(50) for both ErbB2 and FLK-1 is around 1 microM. AG
      879, in combination of PP1 (an inhibitor specific for Src kinase family),
      suppresses almost completely the growth of RAS-induced sarcomas in nude mice. In
      this paper we demonstrate that AG 879 even at 10 nM blocks the specific
      interaction between the Tyr-kinase ETK and PAK1 (a CDC42/ Rac-dependent Ser/Thr
      kinase) in cell culture. This interaction is essential for both the RAS-induced
      PAK1 activation and transformation of NIH 3T3 fibroblasts. However, AG 879 at 10
      nM does not inhibit either the purified ETK or PAK1 directly in vitro, suggesting
      that this drug blocks the ETK-PAK1 pathway by targeting a highly sensitive kinase
      upstream of ETK. Although the Tyr-kinases Src and FAK are known to activate ETK
      directly, Src is insensitive to AG 879, and FAK is inhibited by 100 nM AG 879,
      but not by 10 nM AG879. The structure-function relationship analysis of AG 879
      derivatives has revealed that both thio and tert-butyl groups of AG 879, but not
      (thio) amide group, are essential for its biological function (blocking the ETK
      PAK1 pathway), suggesting that through the (thio) amide group, AG 879 can be
      covalently linked to agarose beads to form a bioactive affinity ligand useful for
      identifying the primary target of this drug.

PMID- 14726664
TI  - Defective control of mitotic and post-mitotic checkpoints in poly(ADP-ribose)
      polymerase-1(-/-) fibroblasts after mitotic spindle disruption.
AB  - Poly(ADP-ribose) polymerase-1 (PARP), a DNA damage-responsive nuclear enzyme
      present in higher eukaryotes, is well-known for its roles in protecting the
      genome after DNA damage. However, even without exogenous DNA damage, PARP may
      play a role in stabilizing the genome because cells or mice deficient in PARP
      exhibit various signs of genomic instability, such as tetraploidy, aneuploidy,
      chromosomal abnormalities and susceptibility to spontaneous carcinogenesis.
      Normally, cell cycle checkpoints ensure elimination of cells with genomic
      abnormalities. Therefore, we examined efficiency of mitotic and post-mitotic
      checkpoints in PARP-/- and PARP+/+ mouse embryonic fibroblasts treated with
      mitotic spindle disrupting agent colcemid. PARP+/+ cells, like most mammalian
      cells, eventually escaped from spindle disruption-induced mitotic checkpoint
      arrest by 60 h. In contrast, PARP-/- cells rapidly escaped from mitotic arrest
      within 24 h by downregulation of cyclin B1/CDK-1 kinase activity. After escaping
      from mitotic arrest; both the PARP genotypes arrive in G1 tetraploid state, where
      they face post-mitotic checkpoints which either induce apoptosis or prevent DNA
      endoreduplication. While all the G1 tetraploid PARP+/+ cells were eliminated by
      apoptosis, the majority of the G1 tetraploid PARP-/- cells became polyploid by
      resisting apoptosis and carrying out DNA endoreduplication. Introduction of PARP
      in PARP-/- fibroblasts partially increased the stringency of mitotic checkpoint
      arrest and fully restored susceptibility to G1 tetraploidy checkpoint-induced
      apoptosis; and thus prevented formation of polyploid cells. Our results suggest
      that PARP may serve as a guardian angel of the genome even without exogenous DNA
      damage through its role in mitotic and post-mitotic G1 tetraploidy checkpoints.

PMID- 14726665
TI  - Genome organization in three dimensions: thinking outside the line.
AB  - Gene organization on nuclear chromosomes is usually depicted as a linear array,
      but at least some regions of the genome are localized to specific subnuclear
      positions in interphase nuclei. Studies in yeast have found that centromeres and
      telomeres are found around the nuclear periphery, and that tRNA genes are
      gathered at the nucleolus, along with the ribosomal RNA gene cluster. These 325
      loci alone impose significant constraints on the three dimensional organization
      of chromosomes in the nucleus, and there is mounting experimental evidence that
      transcription by RNA polymerase II is strongly affected by proximity to these
      regions. Given these observations, one consideration in understanding nuclear
      gene regulation might be the degree to which spatial positioning affects at least
      a subset of gene families.

PMID- 14726666
TI  - A novel anti-vascular therapy for cancer.

PMID- 14726667
TI  - Effects of a selective cyclooxygenase-2 inhibitor on cancer cells in vitro.
AB  - The cyclooxygenase (COX) family of enzymes has been implicated in cell
      proliferation and angiogenesis in many tumors, including colon cancer. Indeed,
      cyclooxygenase-2 (COX-2) inhibitors recently have been approved for use for
      prophylaxis in individuals with familial adenomatous polyposis. We now report on
      the effects of a selective COX-2 inhibitor, celecoxib, on cell proliferation,
      matrix metalloproteinase (MMP) concentration, angiogenesis using an in vitro
      assay, and apoptosis in several human cancer cell lines. We demonstrate that
      celecoxib modestly reduces proliferation in some cell lines and does not affect
      MMP concentrations. However, celecoxib significantly decreases microtubule
      formation in stimulated human umbilical vein endothelial cells (HUVECs) exposed
      to cancer cell supernatants, an in vitro angiogenesis model, when compared to
      controls incubated with supernatants from untreated cells. Celecoxib does not
      consistently induce apoptosis in these cell lines, as determined by DNA laddering
      in agarose gels and by a caspase assay. Thus, it appears that COX-2 inhibitors
      have beneficial effects in reducing malignant cell behavior in vitro and warrant
      further study to elucidate their mechanisms of action and to examine their
      mechanisms of action in this role and their utility in vivo in a variety of
      animal and human tumors.

PMID- 14726669
TI  - Getting back on track, or what to do when apoptosis is de-railed: recoupling
      oncogenes to the apoptotic machinery.
AB  - Programmed cell death or apoptosis is of fundamental importance to cancer as it
      both limits tumorigenesis and is also triggered by many cancer chemotherapeutics.
      Many oncogenes that deregulate the cell cycle also trigger apoptosis, so
      eliminating cells that are proliferating inappropriately. To acquire a complete
      neoplastic phenotype, cancer cells often acquire mutations that compromise the
      apoptotic process, allowing these cells to escape both normal growth constraints
      but to also become resistant to many anti-cancer drugs and leading to the
      emergence of drug-resistant malignancies. Thus discovering how oncogenes are
      coupled to apoptosis and how these links are compromised in cancer is central to
      both understanding cancer progression and developing new therapies to counter
      chemo-resistant cancers. This review will consider how oncogenes activate
      apoptosis and how this response is subverted in cancer cells with a focus on the
      proposed therapeutic strategies that exploit these changes.

PMID- 14726670
TI  - Cell cycle regulation in hematopoietic stem/progenitor cells.
AB  - Hematopoietic stem cells (HSCs) are characterized by pluripotentiality and a
      capacity for self-renewal. In order to both maintain a supply of mature blood
      cells and not to exhaust HSCs throughout the lifespan of the organism, most HSCs
      remain quiescent and only a limited number enter the cell cycle. In HSCs, the
      cell cycle is crucially regulated by external factors such as cytokines and
      interactions with stromal cells and the extracellular matrix (ECM) in the bone
      marrow (BM) microenvironment. In addition, intrinsic transcription factors
      expressed in HSCs, including c-Myb, GATA-2, HOX family proteins, and Bmi-1, also
      control their growth through their effect on gene transcription. In terms of the
      particular roles in regulation of the cell-cycle, p21WAF1 (p21) and p27KIP1 (p27)
      were shown to maintain the quiescence of HSCs and of progenitor cells,
      respectively, thereby governing their available pool sizes. Also, p16INK4A (p16)
      and p15INK4B (p15) are thought to act as tumor suppressors, since their
      inactivation and/or deletion are observable in various types of hematologic
      malignancies. These results make evident that appropriate cell cycle control,
      particularly at the early stage of stem/progenitor cells, is required for
      maintaining normal hematopoiesis.

PMID- 14726671
TI  - Genetic systems for the diagnosis and treatment of human disease.

PMID- 14726672
TI  - Fibronectin alters cell survival and intracellular signaling of confluent A549
      cultures after irradiation.
AB  - Cell-cell and cell-extracellular matrix contacts influence cellular sensitivity
      to ionizing radiation. To further define the influence of these interactions on
      tumor cell survival and cell cycle progression after irradiation without or in
      combination with the phorbol ester phorbol-12-myristate-13-acetate (PMA), the
      radiation response of p53 wild-type A549 lung cancer cells grown on polystyrene,
      fibronectin (FN) or BSA was examined. Confluently growing and log-phase A549 cell
      cultures irradiated on FN showed significantly greater survival compared to cells
      irradiated on polystyrene or BSA. There was a significantly greater elevation of
      G(2)/M cells in FN cultures after irradiation compared to other culture
      conditions. PMA reduced radiation survival on all three substrata and under both
      log-phase and confluent culture conditions, but had no effect on the elevation of
      G(2)/M cells in FN cultures. Induction of Chk1 phosphorylation by irradiation was
      only seen in FN cultures. Chk2 and Cdk1 phosphorylation and Cdc25C expression
      also differed between FN and polystyrene cultures. Induction of p53 and p21 by
      irradiation was modulated but not inhibited by PMA, as were changes in cyclin D1
      and pRb. Changes in protein expression and phosphorylation of these cell cycle
      regulatory proteins coincided tightly with accumulation of cells in G(2)/M after
      irradiation. These findings clearly demonstrate the influence of both
      intercellular and cell-substratum interactions on the radiation response without
      or in combination with PMA and differentiate between the cell survival and cell
      cycle effects of FN attachment.

PMID- 14726673
TI  - Apoptosis and calcium: new roles for cytochrome c and inositol 1,4,5
      trisphosphate.
AB  - Mounting evidence suggests that calcium released from internal stores plays a
      critical role in the progression of apoptosis. The primary calcium release
      channel on endoplasmic reticulum membranes is the inositol 1,4,5-trisphosphate
      receptor (IP3R). Deletion of the gene for IP3R results in defects in apoptosis in
      response to multiple stimuli. Conversely, augmented IP3R levels are associated
      with increased cell death. A mechanistic basis for altered IP3R function during
      apoptosis was revealed with the discovery that cytochrome c binds to IP3R early
      in apoptosis. This interaction blocks the calcium-dependent inhibition of IP3R
      function, resulting in increased calcium release from internal stores. The
      resultant cytoplasmic and mitochondrial calcium overload culminates in cell-wide
      cytochrome c release and maximal caspase activation. These findings highlight the
      importance of intracellular calcium stores in apoptosis, and the multi-functional
      role of cytochrome c released from mitochondria in cell death.

PMID- 14726674
TI  - Inhibition of cell survival and invasive potential of colorectal carcinoma cells
      by the tyrosine kinase inhibitor STI571.
AB  - Inhibiting tyrosine kinases has recently emerged as a therapeutic modality in
      several forms of neoplasia. The tyrosine kinase inhibitor STI571 (IMATINIB
      MESYLATE; GLEEVEC; GLIVEC) is a case in point as it has shown promise in the
      treatment of malignancies expressing the BCR/ABL fusion protein. In addition to
      BCR/ABL, STI571 inhibits the tyrosine kinase moieties of several cell surface
      receptors including the platelet-derived growth factor (PDGF) receptors and c
      Kit. Previous work demonstrated that c-Kit activation supports migration,
      invasion and, survival of certain colorectal carcinoma cells including DLD-1.
      Here we describe that blocking c-Kit with STI571 inhibits these malignant traits
      not only in DLD-1 cells but also in two early passage colorectal carcinoma cell
      strains. Specifically, STI571 inhibited anchorage-independent colony formation
      and cell scattering in semi-solid medium. Furthermore, it enhanced apoptosis
      susceptibility and abrogated invasion of DLD-1 cells through Matrigel. In
      addition, STI571 treatment affected the balance of the Bcl-2 family of apoptosis
      regulators on favor of a pro-apoptotic phenotype. Specifically, STI571 treatment
      of DLD-1 cells was associated with lower levels of Bcl-2 expression accompanied
      by de novo expression of Bcl-xS. Finally, STI571 acted as a chemosensitizing
      agent in DLD-1 cells when used in combination with 5-fluorouracil.

PMID- 14726675
TI  - p21(WAF1/CIP1) mediates the growth response to TGF-beta in human epithelial
      cells.
AB  - We investigated the mechanism by which cancers evade the growth inhibitory
      effects of TGF-beta. Using two p21-/- somatically deleted human epithelial cell
      lines, we find that TGF-beta serves as a growth stimulator rather than a growth
      suppressor to cells lacking p21. In addition, TGF-beta stimulated p21-/- cells
      exhibited a mesenchymal phenotype, demonstrated by an upregulation of vimentin
      and decreased expression of E-cadherin. Analysis of primary human breast cancers
      by immunohistochemical labeling confirmed a correlation between p21 loss and
      positive vimentin expression. These data provide a molecular mechanism explaining
      how nongastrointestinal cancers can escape the anti-proliferative effects of this
      cytokine and simultaneously use this pathway for growth advantage.

PMID- 14726676
TI  - Evaluation of microsatellite instability, hMLH1 expression and hMLH1 promoter
      hypermethylation in defining the MSI phenotype of colorectal cancer.
AB  - INTRODUCTION: About 15% of all colorectal cancers (CRCs) demonstrate high levels
      of microsatellite instability (MSI-H) and are currently best identified by
      molecular analysis of microsatellite markers. Most sporadic CRCs with MSI-H are
      known to be associated with the methylation of the hMLH1 promoter. Promoter
      methylation coincided with lack of hMLH1 expression. We aimed to investigate the
      association between MSI status, hMLH1 protein expression and methylation status
      of the hMLH1 promoter, and to determine the usefulness of each method in defining
      the MSI phenotype in sporadic CRCs. MATERIALS AND METHODS: CRCs from 173 patients
      from the Cancer and Leukemia Group B (CALGB) were assessed for their MSI status.
      An additional cohort of 18 MSI-H tumors from the University of California San
      Diego (UCSD) was included in the analysis of the MSI-H subgroup. MSI testing was
      performed by PCR using five standard MSI markers. hMLH1 promoter analysis was
      investigated by methylation specific PCR (MSP), and expression of the MMR genes
      hMLH1 and hMSH2 was examined by immunohistochemistry (IHC). RESULTS: Of the 173
      CALGB tumors, 111 (64%) were MSS, 35 (20%) were MSI-L and 27 (16%) MSI-H,
      respectively. Data on hMLH1 protein expression, hMSH2 protein expression and
      hMLH1 methylation are available on 128, 173 and 81 of these tumors, respectively.
      Presence of hMLH1 and hMSH2 protein expression was significantly associated with
      MSI status. Four of 45 (8.9%) MSI-H tumors and 0 of 146 (0%) MSS/MSI-L tumors did
      not express hMSH2 (p = 0.0028). hMLH1 protein expression was present in 107 of
      108 (99%) MSS and MSI-L tumors versus 11 of 20 (55%) MSI-H tumors (p < 0.0001).
      Of 61 MSS and MSI-L cancers studied for methylation, 11 (18%) were methylated at
      the hMLH1 promoter whereas 14 of 20 (70%) MSI-H cancers were methylated (p =
      0.0001). In 27 MSI-H tumors studied for hMLH1 protein expression and methylation,
      93% of tumors with loss of expression (93%) were also methylated while 42% (5/12)
      with positive immunostaining for hMLH1 were methylated at the hMLH1 promoter (p =
      0.009). CONCLUSIONS: Promoter methylation and hMLH1 expression are significantly
      associated with the MSI-H phenotype in CRC. Promoter methylation analysis
      provides a useful means to screen for MSI-H tumors. Our data further suggests
      that hMLH1 promoter methylation analysis alone cannot replace MSI testing, as a
      significant number of MSI-H tumors could be potentially overseen by such an
      approach. We suggest that phenotypic evaluation of CRC is performed most reliably
      with MSI testing, although expression analysis and investigation of the promoter
      methylation status may complement the screening process.

PMID- 14726677
TI  - Leukemic transformation.
AB  - Leukemia results from the uncontrolled accumulation of primitive, poorly
      differentiated blood cells, and is a consequence of the accumulation of mutations
      in hematopoietic precursor cells. These mutations include point mutations (single
      base pair insertions, deletions, or substitutions), gross chromosomal
      rearrangements such as deletions, insertions, amplifications, and translocations,
      and epigenetic changes. It seems likely that mutations affecting at least two
      pathways are required for the development of leukemia. One of these pathways
      regulates cell accumulation; the second regulates hematopoietic differentiation.
      Molecularly targeted therapy, which interrupts functions of the leukemogenic
      proteins generated by mutations, has been developed and shown to be effective for
      several forms of malignancy. Therefore, it is our hope and belief that a clearer
      understanding of the mechanism(s) that underlie leukemic transformation will lead
      to effective new therapies for this dreaded disease.

PMID- 14726678
TI  - Cdc20 in S-phase: the Banquo at replication's banquet.
AB  - The Anaphase Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase that
      covalently attaches ubiquitins onto proteins to target them for proteolysis by
      the 26S proteasome. During mitosis, the APC/C is instrumental in allowing the
      cell to enter and exit from mitosis. The APC/C accomplishes this by using
      different specificity factors to recognize, interact with, and ubiquitylate key
      proteins that block cell cycle progression. The specificity factors, Cdc20p and
      Cdh1p, are not always associated with the APC/C and indeed they have the ability
      to interact with substrates in isolation. The molecular events that take place in
      order for Cdc20p and Cdh1p to couple substrates and APC/C are currently being
      resolved. Meanwhile, evidence has emerged suggesting that at least one of the
      specificity factors, Cdc20p, might be capable of functioning independently of the
      APC/C.

PMID- 14726679
TI  - Coupling apoptosis resistance to the cellular stress response: the IAP-Hsp90
      connection in cancer.
AB  - Understanding how tumor cells manage to survive and proliferate in ever-changing
      and often harmful microenvironments is a daunting challenge in tumor biology, and
      a major cause of treatment failure in the oncology clinic. Recent data have now
      demonstrated a direct link between the molecular chaperone Hsp90 and survivin, a
      dual regulator of cell proliferation and cell death over-expressed in virtually
      every human tumor. While the survivin-Hsp90 association may help tumor cells
      elevate their anti-apoptotic threshold and promote their proliferation, it may
      also provide new opportunities for rational cancer therapy.

PMID- 14726680
TI  - Histone, H1.2: another housekeeping protein that kills.
AB  - Histone H1.2, a housekeeping protein that binds nucleosomal linkers, has recently
      been identified as an apoptogenic factor released from the nucleus to the cytosol
      in response to double strand DNA breaks. In the cytosol, it promotes the
      activation of proapoptotic Bcl-2 family proteins, mitochondrial cytochrome c
      release, and ultimately, cell death.

PMID- 14726681
TI  - The ARF-B23 connection: implications for growth control and cancer treatment.
AB  - The tumor suppressor ARF induces a p53-dependent and -independent cell cycle
      arrest. Unlike nucleoplasmic localized MDM2 and p53, ARF localizes in the
      nucleolus. The role of ARF in the nucleolus and the molecular target and
      mechanism of ARF's p53-independent function remain both controversial and a
      fertile field of research. Recent study has identified the nucleolar protein B23
      as a target of ARF for implementing its growth inhibitory function. The ability
      of ARF to block cell cycle progression through the MDM2-p53 pathway and to
      suppress ribosomal biogenesis through B23 suggest a role for ARF in coordinating
      inhibitions of growth and proliferation.

PMID- 14726682
TI  - Mammalian cell cycles without cyclin E-CDK2.
AB  - The family of mammalian E-type cyclins is composed of two proteins, termed cyclin
      E1 and E2. These two cyclins are widely expressed in proliferating cells. E
      cyclins bind and activate cyclin dependent kinase CDK2. Cyclin E-CDK2 complexes
      were believed to play critical function in driving cell cycle progression of
      normal, nontransformed cells and of cancer cells. Several recent reports
      challenge this notion.

PMID- 14726683
TI  - Methylation and regulation of expression of different retinoic acid receptor beta
      isoforms in human colon cancer.
AB  - Tumor suppressor genes can become inactivated in cancer via hypermethylation of
      their promoter. The retinoic acid receptor beta (RARbeta) gene is expressed from
      two distinct promoters, both of which have CpG islands. RARbeta1 is expressed
      primarily during embryogenesis, whereas RARbeta2 is expressed in adult tissues
      and hypermethylated in a number of cancer cells. We used combined bisulfite
      restriction analysis to evaluate their methylation in colorectal mucosa and
      tumors. Methylation of RARbeta1 was detected, with a mean of 2% in normal colon
      tissues in young subjects (< 32 years), and 16% in older subjects (> 75 years) (P
      < 0.001). Using paired normal/tumor tissue samples, we found higher mean
      methylation rate in tumors than in adjacent normal tissue (mean, 46% versus 16%;
      P < 0.001) and hypermethylation of RARbeta1 in all eight cell lines examined. By
      RT-PCR, RARbeta1 was not expressed in normal adult colon tissues and its
      expression could not be efficiently activated in most cell lines by the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR). RARbeta2
      methylation was also observed in normal colon tissues and was lower in young
      individuals than in older ones (mean, 11% versus 23%; P < 0.05). Among paired
      samples, RARbeta2 methylation was higher in tumor tissue than in normal tissue in
      14 cases, vice versa in 7 cases, and equal in 6 cases. All eight cell lines were
      hypermethylated and did not express RARbeta2, but RARbeta2 expression could be
      reactivated easily by 5-Aza-CdR. We suggest that the embryonic RARbeta1 isoform
      is readily hypermethylated in aging colon mucosa and all colorectal cancers
      because of its lack of expression in normal tissues. The adult RARbeta2 isoform
      also shows age-related methylation in normal tissues but more variable
      methylation in colorectal cancer, perhaps because its expression offers continued
      protection against methylation or its silencing does not provide a selective
      advantage in the early stages of the disease.

PMID- 14726684
TI  - Pharmacodynamic behavior of liposomal antisense oligonucleotides targeting Her
      2/neu and vascular endothelial growth factor in an ascitic MDA435/LCC6 human
      breast cancer model.
AB  - The nature of anti-cancer therapeutics is currently undergoing a paradigm change,
      with biologic agents slowly being introduced into the therapeutic armory,
      displacing or complimenting the traditionally used cytotoxic agents. These new
      agents include monoclonal antibodies, recombinant DNA, antisense oligonucleotides
      (ASO) and others. To assess the new therapeutics, new predictive models are
      required. Utilizing the MDA435/LCC6 human breast cancer xenograft model, the
      pharmacokinetic behavior of antisense oligonucleotides targeted against vascular
      endothelial growth factor and HER-2/neu was assessed. For pharmacodynamic
      analysis, ASO in buffer or encapsulated in a liposomal formulation were injected
      intravenously or intraperitoneally into MDA435/LCC6 ascites tumor-bearing mice.
      Plasma antisense elimination, tissue distribution, total peritoneal antisense and
      peritoneal cell associated antisense levels were determined. Liposomal
      encapsulation led to significant decreases in the plasma elimination rate, as
      evidenced by an approximate 10-fold increase in mean AUC over 24 hours, as well
      as enhanced peritoneal cell delivery in mice bearing ascites tumors. Tissue
      distribution studies of both free and liposome encapsulated ASO indicated that
      ASO distribution was dictated primarily by the liposomal carrier when
      administered in liposomal form.

PMID- 14726685
TI  - Knockdown of Chk1, Wee1 and Myt1 by RNA interference abrogates G2 checkpoint and
      induces apoptosis.
AB  - Mammalian cells undergo cell cycle arrest in response to DNA damage due to the
      existence of multiple checkpoint response mechanisms. One such checkpoint pathway
      operating at the G(1) phase is frequently lost in cancer cells due to mutation of
      the p53 tumor suppressor gene. However, cancer cells often arrest at the G(2)
      phase upon DNA damage, due to activation of another checkpoint pathway that
      prevents the activation Cdc2 kinase. The kinases, Chk1, Wee1, and Myt1 are key
      regulators of this G(2) checkpoint, which act directly or indirectly to inhibit
      Cdc2 activity. Here we show that RNA interference (RNAi)-mediated downregulation
      of Wee1 kinase abrogated an Adriamycin trade mark -induced G(2) checkpoint in
      human cervical carcinoma Hela cells that are defective in G(1) checkpoint
      response. Wee1 downregulation sensitized HeLa cells to Adriamycin trade mark 
      induced apoptosis. Downregulation of Chk1 kinase in Hela cells also caused a
      significant amount of cell death in dependent of DNA damage. In contrast, Myt1
      downregulation also abrogated Adriamycin trade mark -induced G(2) arrest but did
      not cause substantial apoptosis. Reduction in Wee1, Chk1, or Myt1 levels did not
      sensitize normal human mammary epithelial cells (HMEC) cells to Adriamycin trade
      mark -induced apoptosis unlike the situation in Hela cells. Our study reveals
      distinct roles for Chk1, Wee1, and Myt1 in G(2) checkpoint regulation. The data
      reported here support the attractiveness of Wee1 and Chk1 is as molecular targets
      for abrogating the G(2) DNA damage checkpoint arrest, a situation that may
      selectively sensitize p53-deficient tumor cells to radiation or chemotherapy
      treatment.

PMID- 14726686
TI  - Cytochrome c: a crosslink between the mitochondria and the endoplasmic reticulum
      in calcium-dependent apoptosis.
AB  - Early and pivotal events in apoptosis are now known to occur in the mitochondria
      and the endoplasmic reticulum, and release of cytochrome c from the mitochondria
      and calcium from the endoplasmic recticulum into the cytosol are considered to be
      requisites for apoptosis in response to different stimuli. In the December 2003
      issue of Nature Cell Biology, Boehning et al. report that early in apoptosis
      mitochondrial cyctochrome c translocates to the endoplasmic reticulum where it
      specifically binds inositol (1,4,5) triphosphate receptors, leading to sustained
      calcium release. The released calcium then triggers a mass exodus of cytochrome c
      from all mitochondria in the cells, thus amplifying the apoptotic signal.

PMID- 14726687
TI  - APC activators caught by their tails?
AB  - The complexity of the Anaphase-Promoting Complex (APC), the major ubiquitin
      ligase in mitotic control, has been puzzling investigators ever since its
      discovery. Recent biochemical and genetic studies have now provided insights not
      only into the architecture of the complex, but also into how activators are
      recruited to the APC. In this article, we discuss the implications of these
      findings on our current understanding of APC activation.

PMID- 14726688
TI  - Expression of inducible Bcl-X(S) in myeloid leukemia: compensatory upregulation
      of Bcl-X(L) and Bcl-2 prevents apoptosis and chemosensitization.
AB  - Programmed cell death and survival are controlled by complex pathways, with the
      anti-apoptotic proteins Bcl-2 and Bcl-X(L) and the pro-apoptotic proteins Bax and
      Bcl-X(S) being major regulators. Variations in the expression of Bcl-X(S) have
      been observed in leukemic cells from acute myeloid leukemia (AML) patients and
      correlated with clinical outcome, but the impact of Bcl-X(S) on molecular
      pathophysiological mechanisms and the potential role of Bcl-X(S) as a therapeutic
      target in AML are not yet defined. In order to analyze the functional relevance
      of Bcl-X(S) in AML, Bcl-X(S) was moderately (2-3 fold) overexpressed in the AML
      cell lines HL-60 and MO7e by transfection with a tetracycline-regulatable Bcl
      X(S) expression system. Increased Bcl-X(S) did not change the rate of spontaneous
      apoptosis, chemosensitivity to ara-C, or cell cycle kinetics. Further analysis of
      this unexpected result revealed a compensatory transcriptional upregulation of
      endogenous anti-apoptotic Bcl-X(L) in MO7e and HL-60, and Bcl-2 in HL-60 cells
      resulting in increased protein levels. Bax levels were unchanged. Bcl-X(L) and
      Bcl-2 were found to heterodimerize with Bcl-X(S), thereby providing a possible
      explanation for the abrogation of its pro-apoptotic function. These results
      suggest the existence of a regulatory mechanism aimed to protect leukemic cells
      from pro-apoptotic stimuli.

PMID- 14726689
TI  - Neosis: a novel type of cell division in cancer.
AB  - Using computerized video time-lapse microscopy, we studied early cellular events
      during carcinogen-induced transformation of C3H10T1/2 cells.
      Multinucleate/polyploid giant cells (MN/PGs) formed due to DNA damage are thought
      to die via mitotic catastrophe. Before they die, some MN/PGs undergo a novel type
      of cell division, termed neosis, characterized by karyokinesis via nuclear
      budding followed by asymmetric, intracellular cytokinesis, producing several
      small mononuclear cells, termed the Raju cells, with extended mitotic life span
      (MLS). Mitotic derivatives of Raju cells give rise to transformed cell lines,
      inherit genomic instability, display a phenotype and transcriptome different from
      the neosis mother cell, and anchorage-independent growth. Neosis of MN/PGs also
      precedes spontaneous transformation of p53-/- mouse cells. Rodent neotic clones,
      and primary and metastatic human tumor cells undergo spontaneous or induced
      secondary/tertiary neosis. Neosis seems to extend the MLS of cells under
      conditions of genetic duress not favoring mitosis. It precedes tumorigenesis,
      occurs several times during tumor progression, yielding tumor-initiating Raju
      cells and introducing tumor cell heterogeneity subject to natural selection
      during tumor progression. Events during neosis, and its relevance to origin of
      established cell lines, multistep carcinogenesis, cancer stem cells, and
      therapeutic advantages of anti-neotic agents (neosicides) are discussed.

PMID- 14726690
TI  - Retinoic acid receptor beta and colon cancer.

PMID- 14726691
TI  - Upregulation of mRNA in MAPK signaling: transcriptional activation or mRNA
      stabilization?
AB  - Mitogen-activated protein kinases (MAPKs), found in all eukaryotes, are signal
      transducing enzymes that play a central role in a variety of biological
      processes. MAPK phosphatase has dual catalytic activity toward phosphotyrosine-
      and phosphothreonine-containing proteins, and is known to inactivate ERKs and
      JNKs/SAPKs, thus playing a crucial role in MAPK regulation. Although MAPK
      phosphatase has been implicated in a feedback loop that inactivates MAPKs after
      stimulation by mitogens and during the cellular response to stress, signaling
      pathways leading to MAPK phosphatase gene expression have not been fully
      elucidated. Recently, we have shown that a novel RNA-binding protein Rnc1 plays a
      crucial role in negative feedback regulation of MAPK signaling by stabilizing the
      mRNA of a MAPK phosphatase at the post-transcriptional level. One important
      aspect of our findings is that the increase in mRNA levels involves not only the
      transcriptional upregulation, but also the post-transcriptional gene regulation,
      especially the regulation of mRNA stability. Our discovery highlights a potential
      role and an emerging view of RNA-binding protein as a regulator of cell signaling
      and as a future target of drug discovery.

PMID- 14726692
TI  - Inhibition of cdk1 by alsterpaullone and thioflavopiridol correlates with
      increased transit time from mid G2 through prophase.
AB  - Current models suggest that cyclin B1/cdk1 regulates the G2 to M transition and
      that its activity is maximal during the period from prophase to metaphase in
      mammalian cells. Although data are lacking, the idea that cyclin B1/cdk1
      regulates the transit time from prophase to metaphase is reasonable. Development
      of small molecule inhibitors of cyclin dependent kinases (cdk's) as cancer
      therapeutics presents an opportunity to evaluate the effects of inhibiting cdk's
      in asynchronous cell populations. Analysis of cdk1 inhibitors is complicated by
      their ability to inhibit other cdk's in vitro at higher concentrations. In this
      study we measured the effects of two cdk1 inhibitors on S, G2, and M transit for
      Hela cells and correlated these effects on cyclin B1/cdk1 and cyclin A/cdk2
      activities. Dose responses demonstrate that low concentrations of both compounds
      inhibited the activity of cdk1 but not cdk2 in HeLa cells. The partial loss of
      cdk1 activity at low doses induced a prophase accumulation during a 3 h period
      and an increased transit time through mitosis. In addition, both inhibitors
      lengthened the G2 transit time with progressively greater effect on mid and late
      G2. High doses of both inhibitors increased the S phase time, which correlated
      with the inhibition of cdk2 activity. These results suggest that cdk1-cyclin
      activity is rate limiting for cell cycle progression during a period from mid G2
      through prophase.

PMID- 14726693
TI  - Emerging pathogenic role for cyclin dependent kinases in neurodegeneration.
AB  - While the requirement of CDKs in cell cycle control is well established, the
      participation of CDK family members in other important biological processes are
      now beginning to be uncovered. Paramount in these newly defined roles is the
      surprising involvement of CDKs in neuronal development and death. These
      discoveries are somewhat of a paradox considering the terminally differentiated
      state of neurons. This brief perspective will focus on the role of CDKs in
      neuronal death and neurodegeneration. In this regard, we will primarily explore
      two (of potentially many) ways by which CDKs may enable neuronal death. The first
      involves the effects of ectopic activation of cell cycle related CDKs in a
      terminal post mitotic environment. The second explores how cdk5, a neuron
      specific cdk required for normal neuronal function, can be usurped to signal
      death.

PMID- 14726694
TI  - SAGE identification and fluorescence imaging analysis of genes and transcripts in
      melanomas and precursor lesions.
AB  - Melanomas of sporadic and familial origin develop in a stepwise fashion in
      approximately 40-80% of all cases; yet, the genetic events governing the
      progression from nevocytic precursor lesions to early and advanced-stage
      melanomas remain largely unknown. In the present study, we provide an analysis of
      genes that were identified in four recently generated primary and metastatic
      melanoma Serial Analysis of Gene Expression (SAGE) libraries. In addition to SAGE
      tags corresponding to transcripts with unknown function, or to unidentified
      transcripts, known genes were identified that hitherto have not been shown to be
      expressed or have a function in early and advanced-stage melanomas and/or
      melanoma precursor lesions. Conducting fluorescence imaging analysis with cyanine
      dye-conjugated antibodies and oligonucleotides, we established the expression
      pattern of ATM, HEI10, PKD1, KAI11, IL-10R, and hypothetical protein FLJ11151 in
      nevus and melanoma specimens.

PMID- 14726695
TI  - Overexpression of ZNRD1 promotes multidrug-resistant phenotype of gastric cancer
      cells through upregulation of P-glycoprotein.
AB  - ZNRD1, a new zinc ribbon gene, has been previously identified as an upregulated
      gene in a multidrug-resistant gastric cancer cell line SGC7901/VCR comparing to
      its parental cell SGC7901 by subtractive hybridization and RT-PCR. The antisense
      nucleic acid for ZNRD1 could enhance adriamycin accumulation in SGC7901/VCR cells
      and sensitize SGC7901/VCR cells to vincristine. The present study aims to explore
      the role of ZNRD1 in multidrug resistance in gastric cancer cells. Upregulation
      of ZNRD1 protein in SGC7901/VCR cells was confirmed by Western blot and
      immunocytochmical staining. ZNRD1 was genetically overexpressed in SGC7901 cells
      by gene transfection. It was found that overexpression of ZNRD1 could sensitize
      SGC7901 cells to P-glycoprotein (P-gp)-related anticancer drugs (vincristine,
      adriamycin, etoposide) but not to P-gp-nonrelated drugs (5-fluorouracil and
      cisplatin), which was accompanied with significantly decreased adriamycin
      accumulation and retention and increased adriamycin releasing in SGC7901 cells.
      Verapamil, an inhibitor for P-gp, could reverse the effects of ZNRD1 on drug
      sensitivity and drug accumulation in SGC7901 cells to a great extent. Western
      blot and Northern blot revealed that overexpression of ZNRD1 could upregulate P
      gp at both protein and mRNA levels. Together, these results suggest that
      overexpression of ZNRD1 could promote multidrug-resistant phenotype of gastric
      cancer cells through upregulation of P-gp.

PMID- 14726696
TI  - An Arf(GFP/GFP) reporter mouse reveals that the Arf tumor suppressor monitors
      latent oncogenic signals in vivo.
AB  - Understanding how the Arf tumor suppressor is activated in response to abnormally
      elevated mitogenic signaling thresholds is a particularly vexing problem. Studies
      of a knock-in mouse strain in which sequences encoding green fluorescent protein
      were substituted for those encoding p19Arf argue that the Arf gene responds to
      latent oncogenic signals in vivo to eliminate incipient cancer cells.

PMID- 14726697
TI  - Synergy between PI3K/Akt and Raf/MEK/ERK pathways in IGF-1R mediated cell cycle
      progression and prevention of apoptosis in hematopoietic cells.
AB  - The insulin like growth factor-1 (IGF-1) receptor (R) induced PI3K/Akt signal
      transduction cascade has critical roles in prevention of apoptosis and regulation
      of cell cycle progression. Here, we discuss the effects of IGF-1R-mediated signal
      transduction on hematopoietic cells which normally require interleukin-3 (IL-3)
      for growth and prevention of apoptosis. Cytokine-dependent FDC-P1 hematopoietic
      cells were conditionally transformed to grow in response to overexpression of IGF
      1R in the presence of IGF-1. When these cells were deprived of IL-3 or IGF-1 for
      24 hrs, they exited the cell cycle, activated caspase 3 and underwent apoptosis.
      The effects of inhibitors which targeted the PI3K/Akt and Raf/MEK/ERK pathways
      were determined. When the cells were cultured with IGF-1 and either PI3K or MEK
      inhibitors, cell cycle progression and DNA synthesis were inhibited and caspase 3
      activity and apoptosis were induced. Coinhibition of both pathways synergized to
      prevent cell cycle progression, inhibit DNA synthesis and induce apoptosis. These
      inhibitors had more apoptotic inducing effects when the cells were grown in
      response to IGF-1 than IL-3, indicating that IL-3 can induce additional anti
      apoptotic pathways. These results demonstrate that the PI3K/Akt and Raf/MEK/ERK
      pathways are intimately involved in IGF-1R-mediated cell cycle progression and
      prevention of apoptosis in hematopoietic cells.

PMID- 14726698
TI  - Analysis of the kar3 meiotic arrest in Saccharomyces cerevisiae.
AB  - The motor protein Kar3p and its associated protein Cik1p are essential for
      passage through meiosis I. In the absence of either protein, meiotic cells arrest
      in prophase I. Experiments were performed to determine whether the arrest was
      caused by a structural inability to proceed through meiosis, or by a regulatory
      mechanism. The data demonstrate that the meiotic arrest is not structural; kar3
      and cik1 mutants are able to form normal looking bipolar spindles and divide
      their DNA into two masses in spo11 mutant backgrounds. To identify the regulatory
      system necessary for the kar3/cik1 meiotic arrest, we tested whether the arrest
      could be bypassed by eliminating the pachytene checkpoint or the spindle
      checkpoint. The arrest is not solely dependent upon the pachytene checkpoint that
      monitors recombination and aspects of chromosome synapsis. Elimination of the
      spindle checkpoint failed to allow kar3 mutants to undergo meiosis I nuclear
      division, but phenotypes of the kar3/spindle checkpoint double mutants suggest
      that the kar3 meiotic arrest may be mediated by the spindle checkpoint.

PMID- 14726699
TI  - Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU
      family transcription factor.
AB  - The Brn-3b POU family transcription factor has previously been shown to be over
      expressed in human breast cancer and to enhance the growth rate and anchorage
      independent growth of human breast cancer cells, acting at least in part by
      inhibiting the expression of the BRCA-1 anti-oncogene. Here we have used gene
      arrays to identify several other targets for Brn-3b in human breast cancer cells,
      including cyclin-dependent kinase 4 (CDK4). In particular, we show that levels of
      CDK4 mRNA and protein correlate with the levels of Brn-3b in breast cancer cell
      lines manipulated to express different levels of Brn-3b and in human breast
      cancer biopsies and that Brn-3b can activate the CDK4 promoter. The effect of Brn
      3b on the growth regulatory CDK4 protein provides a further mechanism by which
      Brn-3b can regulate breast cancer cell growth and indicates that it can do this
      by activating as well as repressing specific target genes.

PMID- 14726700
TI  - The genetics of FANCC and FANCG in familial pancreatic cancer.
AB  - Patients with Fanconi anemia (FA) display a wide variety of defects including
      bone marrow failure and a high risk of developing cancer. Multiple Fanconi genes
      exist whose proteins form a complex that along with BRCA1 is important for the
      translocalization of FANCD2 to nuclear foci. With BRCA2 and RAD51, this complex
      is thought to have a role in the repair of DNA double strand breaks. The genetic
      basis of another form of Fanconi anemia--FANCD1, was recently identified as the
      result of biallelic inactivating mutations of the BRCA2 gene. Since carriers of
      germline BRCA2 gene mutations have an increased risk of developing pancreatic
      cancer, the FA pathway has been investigated as a tumor suppressor pathway in
      pancreatic cancer. Recently van der Heijden et al. identified FANCC and FANCG
      gene mutations in patients with young-onset pancreatic cancer. Here, we
      determined the role of germline FA gene mutations in kindred in which several
      family members had pancreatic cancer. Sequence analysis of 38 individuals with
      familial pancreatic cancer enrolled in the National Familial Pancreatic Tumor
      Registry (NFPTR) revealed previously identified polymorphisms within two exons
      and one intron of FANCC, and in three introns of FANCG. In addition, an
      unaffected relative from one family contained an exonic polymorphism within the
      FANCC gene. These and published data suggest the possibility that although
      germline and somatic mutations in FANCC and FANCG may contribute to the
      occurrence of pancreatic cancers, the pancreatic cancers that arise do so in an
      apparent sporadic fashion rather than with a phenotype of familial pancreatic
      cancer. FANCC and FANCG mutations may have low penetrance for the pancreatic
      cancer phenotype.

PMID- 14726701
TI  - Extracellular matrix composition modulates cell cycle checkpoint control: a new
      twist to radiation sensitivity.

PMID- 14726702
TI  - Novel therapeutic strategies in prostate cancer.
AB  - Prostate cancer is the most common noncutaneous cancer in American men and the
      second most common cause of death. It is estimated that in 2003, 220,900 new
      cases will be diagnosed and 28,900 men will die from the disease.1 Hormonal
      therapy via surgical or chemical castration is the mainstay of treatment for
      metastatic prostate cancer. While this is quite effective initially, with time
      patients become refractory to this treatment and may require additional therapy.
      There have been a substantial number of novel agents that have been developed in
      the last 10 years that show promise in the treatment of patients with prostate
      cancer, when used alone or when combined with current approaches (Table 1).

PMID- 14726704
TI  - Suppression of epithelial cell transformation and induction of actin dependent
      differentiation by dominant negative Rac1, but not Ras, Rho or Cdc42.
AB  - Major cancer therapeutic approaches are based on inhibition of the ras-signaling
      pathway, with special emphasis on the MAPK arm. Transformation progression from
      benign to malignant can be effected by the expression of Rho GTPases, also ras
      effectors. To ascertain whether their inhibition, could suppress progression,
      dominant negative (DN) GTPases were transfected into malignantly transformed
      epithelial cells. N17rac gave rise to cells that, though viable, were severely
      depressed in their growth rate and saturation density, due to increased
      apoptosis. This was in contrast to cells expressing WTrac1 or the other DN
      GTPases, which did not exhibit altered growth kinetics. WTrac1 and N17rac
      transfectants were no longer able to grow in soft agar, unlike the other DN
      GTPase transfectants, which retained their ability to grow in soft agar. Thus,
      not only progression, but transformation per se was suppressed by DNrac1. V12rac1
      alters the expression and localization of the actin regulating proteins vinculin
      and VASP, which results in the loss of stable F-actin structures and actin-based
      differentiation characteristics. In the presence of N17rac1, VASP was
      downregulated and vinculin and F-actin colocalization restored. Consequently, F
      actin structures and their dependent adhesive interactions were reestablished.
      Thus, rac1 and its effectors may also serve as important targets for cancer
      therapeutics.

PMID- 14726703
TI  - Identification of novel survivin-derived CTL epitopes.
AB  - The identification of tumor antigens, which are essential for the survival of
      tumor cells is a new avenue to prevent antigen loss variants emerging due to
      immunoselection, particularly during immune therapy. In the search for such
      immunogenic tumor antigens, we recently identified spontaneous cytotoxic
      lymphocyte (CTL) responses against the inhibitor of apoptosis protein survivin.
      Thus, we identified two HLA-A2-restricted, survivin-derived CTL epitopes, which
      both were targets for spontaneous CTL responses in melanoma, breast cancer, and
      CLL. Here, we extend these data and describe the characterization of novel HLA-A1
      , HLA-A2-, HLA-A3-, and HLA-A11-restricted survivin epitopes on the basis of
      spontaneous CTL responses in cancer patients. These epitopes significantly
      increase the number of patients eligible for immunotherapy based on survivin
      derived peptides. Additionally, the collective targeting of several restriction
      elements is likely to decrease the risk of immune escape by HLA-allele loss.

PMID- 14726705
TI  - Rac transformation: the actin connection.

PMID- 14726707
TI  - Glioma growth inhibition by selective COX-2 inhibitors via cyclooxygenase
      independent pathways: implications for therapy.

PMID- 14726706
TI  - Cell cycle control: a complex issue.
AB  - Do p27Kip1 and p21Cip1 function as activators or inhibitors of D cyclin-cdk4
      activity? Attempts to answer this question, and thus to understand how cdk4--a
      key cell cycle regulator--becomes active, have produced conflicting data. In this
      perspective, we summarize the results of studies addressing the effects of
      p27Kip1 and p21Cip1 on the assembly and activation of D cyclin-cdk4 complexes.
      Emphasis is placed on our experimental findings that support a model of cell
      cycle control in which p27Kip1 and p21Cip1 stabilize D cyclin-cdk4 complexes but
      inhibit D cyclin-cdk4 activity.

PMID- 14726708
TI  - Executing cell senescence.
AB  - Senescence is a permanent form of cell cycle arrest that limits the proliferation
      of damaged cells and may contribute to tumor suppression and aging. We recently
      demonstrated that some senescent cell types undergo dramatic changes in chromatin
      organization that are dependent on the retinoblastoma protein and are associated
      with the stable repression of some E2F target genes. Here we show how these
      changes might contribute to the stability of the senescent state.

PMID- 14726709
TI  - Linear model of colon cancer initiation.
AB  - Cancer results if regulatory mechanisms of cell birth and death are disrupted.
      Colorectal tumorigenesis is initiated by somatic or inherited mutations in the
      APC tumor suppressor gene pathway. Several additional genetic hits in other tumor
      suppressor genes and oncogenes drive the progression from polyps to malignant,
      invasive cancer. The majority of colorectal cancers present chromosomal
      instability, CIN, which is caused by mutations in genes that are required to
      maintain chromosomal stability. A major question in cancer genetics is whether
      CIN is an early event and thus a driving force of tumor progression. We present a
      new mathematical model of colon cancer initiation assuming a linear flow from
      stem cells to differentiated cells to apoptosis. We study the consequences of
      mutations in different cell types and calculate the conditions for CIN to precede
      APC inactivation. We find that early emergence of CIN is very likely in
      colorectal tumorigenesis.

PMID- 14726710
TI  - Inhibition of G1 to S cell cycle progression by BCCIP beta.
AB  - The BCCIP alpha protein was identified as a BRCA2 and CDKN1A (p21, or
      p21(Waf1/Cip1)) Interacting Protein. It binds to a highly conserved domain
      proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK
      inhibitor p21. Previous reports showed that BCCIP alpha enhances the inhibitory
      activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain
      tumor cells. Here we show that a second isoform, BCCIP beta, also binds to p21
      and inhibits cell growth. The growth inhibition by BCCIP beta can be partially
      abrogated in p21 deficient cells. Overexpression of BCCIP beta delays the G1 to S
      progression and results in an elevated p21 expression. These data suggest BCCIP
      beta as a new regulator for the G1-S cell cycle progression and cell growth
      control.

PMID- 14726711
TI  - Erk2 signaling and early embryo stem cell self-renewal.
AB  - Differentiation of the mammalian blastocyst generates two distinct cell lineages:
      the trophectoderm, which contributes to the trophoblast layers of the placenta,
      and the inner cell mass, which forms the embryo. We and others recently
      demonstrated that the MAP kinase ERK2 is essential for trophoblast development.
      Erk2 mutant embryos fail to form extra-embryonic ectoderm and the ectoplacental
      cone, suggesting a role for ERK2 activation in the proliferation of trophoblast
      stem (TS) cells. Previous studies have documented that ERK1/2 activity is
      dispensable for proliferation of embryonic stem (ES) cells and rather interferes
      with self-renewal. Thus, signaling by the ERK1/2 MAP kinase pathway appears to be
      critical for the regulation of self-renewal and propagation of early embryo stem
      cell populations.

PMID- 14726712
TI  - Expression analysis of genes identified by molecular profiling of VGP melanomas
      and MGP melanoma-positive lymph nodes.
AB  - Microarray profiling is a powerful approach to establish gene expression patterns
      for different histopathological stages of a malignancy, and at the same time, to
      identify individual genes that may have important functions in the early and/or
      advanced stages of a neoplasm. To identify genes that hitherto have not been
      shown to be expressed or play a role in advanced-stage melanomas, we conducted
      microarray analyses with RNAs from primary melanoma and melanoma-positive lymph
      node specimens. Using RT-PCR, quantitative, real-time RT-PCR, and fluorochrome
      oligonucleotide-based optical imaging, we established the level and pattern of
      expression of five of the identified known genes [Suppression of Tumorigenicity
      13 (ST13), Cystatin 8 (CST-8), Dyskeratosis Congentia 1 (DKC1), Neuroendocrine
      Secretory Protein 55 (NESP55), Niemann-Pick Disease, type C2 (NP-C2)], and a gene
      with unknown function (16.7 kD Hypothetical Protein) in benign and atypical
      nevocytic lesions, advanced-stage melanomas, and melanoma-positive lymph nodes.

PMID- 14726713
TI  - HIF-1: an oxygen and metal responsive transcription factor.
AB  - Normal development and function of metazoan organisms depend on oxygen
      availability. The level of oxygen can be sensed by individual cells, which
      respond to reduced oxygenation (hypoxia) largely through activation of hypoxia
      inducible factor-1 (HIF-1). At the organism level the response to hypoxia
      involves an increase in red blood cell production. Within tissues, HIF activation
      increases the blood supply and blood vessel growth. At the individual cell level
      it is manifested as an increase in anaerobic metabolism in order to sustain basic
      cellular functions. Iron is central to the oxygen sensing mechanism, and
      sensitivity to other metals, namely cobalt and nickel, is a distinctive feature
      of the HIF system; in fact, this is often used as an initial way of implicating
      HIF-1 in a biological response. Historically, the fact that nickel or cobalt
      mimicked hypoxia provided an important clue as to the nature of the oxygen
      sensing mechanism. It also raises the possibility that nickel or cobalt exposure
      may have important toxic and pathological effects mediated by HIF activation.
      Here we review the implications of the metal sensitivity of the HIF-1 system, and
      examine the hypothesis that HIF-1 activation may play an important role in metal
      induced carcinogenesis.

PMID- 14726714
TI  - Recent advances in cell biology, diagnosis, and therapy of gastrointestinal
      stromal tumor (GIST).
AB  - The understanding of mesenchymal neoplasms of the gastrointestinal tract has
      evolved dramatically over the last two decades since gastrointestinal stromal
      tumor (GIST) was described as the most common stromal tumor arising anywhere from
      the esophagus to the ano-rectum. Although morphologically similar to other benign
      and malignant smooth muscle and neural stromal neoplasms, GIST constitutes a
      distinct group of rare gastrointestinal tract tumors that originate from the
      interstitial cells of Cajal, regulators of gut peristalsis that normally express
      CD117, which is the product of the c-KIT proto-oncogene that encodes a tyrosine
      kinase receptor that regulates cellular proliferation in GISTs. Virtually all
      GISTs occur from mutations of the c-KIT oncogene and exhibit consistent
      expression of c-KIT (CD117), which is considered the most specific criterion for
      a diagnosis of GIST. Gastrointestinal stromal tumors vary in their behavior and
      several features have to be considered to assess their malignant potential. The
      advent of sophisticated imaging techniques for the evaluation and sampling of
      stromal tumors of the gastrointestinal tract has resulted in improved detection
      of GISTs. The identification of a novel tumor-specific target in c-KIT resulted
      in the development of a tyrosine kinase-inhibitor (imatinib mesylate) that
      provides an encouraging option for treating GISTs. This article reviews recent
      advances in the understanding of the cell biology, diagnosis, and therapy of
      GISTS.

PMID- 14726715
TI  - Paroxetine and the FDA.

PMID- 14726716
TI  - Lamotrigine and informed consent.

PMID- 14726717
TI  - Web-based teacher SKAMPs.

PMID- 14726718
TI  - ADHD in Omani schoolgirls.

PMID- 14726719
TI  - Psychiatric aspects of child and adolescent obesity: a review of the past 10
      years.
AB  - OBJECTIVE: To review the past 10 years of published research on psychiatric
      aspects of child and adolescent obesity and highlight information mental health
      professionals need for preventing obesity in youths and diagnosing and treating
      it. METHOD: Researchers performed computerized and manual searches of the
      literature and summarized the most relevant articles. RESULTS: The growing
      epidemic of child and adolescent obesity deserves attention for its immediate
      mental health and long-term medical complications. Mental health professionals
      working with obese youths should be aware of recent advances in neuroscience,
      genetics, and etiologies associated with obesity. Those who assess and treat
      obese youth should view obesity as a chronic disease. Currently, no approved
      pharmacological or surgical approaches exist to treat childhood obesity.
      CONCLUSIONS: Health care providers should focus on modest weight-loss goals that
      correlate with significant health benefits. The most effective treatments include
      substantial parental involvement. Mental health professionals should help obese
      children build self-esteem to help them lead full lives regardless of weight.

PMID- 14726720
TI  - Commentary on "psychiatric aspects of child and adolescent obesity: a review of
      the past 10 years".

PMID- 14726721
TI  - Heart rate level and antisocial behavior in children and adolescents: a meta
      analysis.
AB  - OBJECTIVE: To assess whether antisocial children are characterized by low heart
      rate. METHOD: A meta-analysis was conducted on 45 independent effect sizes of the
      resting heart rate-antisocial behavior relationship obtained from 40 studies
      meeting inclusion and exclusion criteria. Studies were conducted between 1971 to
      2002 using a total of 5,868 children. A secondary meta-analysis was also
      conducted on heart rate during a stressor. RESULTS: Significant overall effect
      sizes were found for both resting heart rate (d = -0.44, p <.0001) and heart
      during a stressor (d = -0.76, p <.0001). Gender, age, method of recording, use of
      psychiatric control group, recruitment source, concurrent versus prospective
      nature of testing, and source of behavioral rating all failed to moderate this
      relationship. CONCLUSIONS: Low resting heart rate appears to be the best
      replicated biological correlate to date of antisocial behavior in children and
      adolescents. Several theoretical interpretations of this relationship are
      outlined that should be examined in future studies.

PMID- 14726722
TI  - Errorless academic compliance training: improving generalized cooperation with
      parental requests in children with autism.
AB  - OBJECTIVE: Children with autism often demonstrate distress and oppositionality
      when exposed to requests to complete academic or household tasks. Errorless
      academic compliance training is a success-focused, noncoercive intervention for
      improving child cooperation with such activities. In the present study, the
      authors evaluated treatment and generalization effects of this intervention on
      four children diagnosed with autism. METHOD: In a multiple baseline across
      subjects design, parents delivered a range of academic and nonacademic requests
      to their children to determine the probability of compliance for each request. A
      hierarchy of academic requests ranging from those yielding high compliance (level
      1) to those yielding low compliance (level 4) was then developed. Treatment began
      with the concentrated delivery of level 1 requests, with praise and reward for
      compliant responses. Over several weeks, children were gradually introduced to
      requests from subsequent probability levels with continued reward for compliance.
      RESULTS: High compliance levels were demonstrated throughout and following
      treatment. Evidence of generalization to untrained academic requests and
      nonacademic requests emerged. Treatment gains were maintained up to 6 months
      after treatment. CONCLUSIONS: Errorless academic compliance training appears to
      be an effective intervention for enhancing generalized compliance in children
      with autism.

PMID- 14726723
TI  - Specifying PDD-NOS: a comparison of PDD-NOS, Asperger syndrome, and autism.
AB  - OBJECTIVE: To describe the clinical characteristics of children given a diagnosis
      of pervasive developmental disorder-not otherwise specified (PDD-NOS) by expert
      clinicians and to compare these to the clinical characteristics of children given
      a diagnosis of autism and Asperger syndrome (AS). METHOD: Two hundred sixteen
      children with autism, 33 with AS, and 21 with PDD-NOS were compared on measures
      of level of functioning (communication, daily living and social skills, IQ, and
      age of acquisition of language) and on various symptoms of autism (impaired
      communication and reciprocal social interaction and a preference for repetitive
      and stereotyped activities). RESULTS: In terms of level of functioning measures,
      the PDD-NOS children had scores that were between those of the children with
      autism and those of the children with AS. In contrast, the PDD-NOS group had
      fewer autistic symptoms, especially repetitive stereotyped behaviors, than both
      the autism and AS groups (chi2 = 11.06, p =.004). Children with PDD-NOS could be
      placed into one of three subgroups: a high-functioning group (24%) who resembled
      AS but had transient language delay or mild cognitive impairment; a subgroup
      resembling autism (24%) but who had late age of onset or too severe cognitive
      delays or were too young to potentially meet the full diagnostic criteria for
      autism; and a group (52%) not fulfilling the criteria for autism because of fewer
      stereotyped and repetitive behaviors. CONCLUSIONS: With some revision to current
      diagnostic criteria, a more homogenous atypical group with significant
      impairments in social-communication but fewer repetitive behaviors can be
      differentiated from the more nonspecific PDD-NOS group. This differentiation may
      lead to better reliability in diagnosis and to further progress in studies of
      etiology.

PMID- 14726724
TI  - Commentary: categorical versus spectrum approaches to classification in pervasive
      developmental disorders.

PMID- 14726725
TI  - Multisystemic therapy effects on attempted suicide by youths presenting
      psychiatric emergencies.
AB  - OBJECTIVE: To evaluate the efficacy of multisystemic therapy (MST) in reducing
      attempted suicide among predominantly African American youths referred for
      emergency psychiatric hospitalization. METHOD: Youths presenting psychiatric
      emergencies were randomly assigned to MST or hospitalization. Indices of
      attempted suicide, suicidal ideation, depressive affect, and parental control
      were assessed before treatment, at 4 months after recruitment, and at the 1-year
      posttreatment follow-up. RESULTS: Based on youth report, MST was significantly
      more effective than emergency hospitalization at decreasing rates of attempted
      suicide at 1-year follow-up; also, the rate of symptom reduction over time was
      greater for youths receiving MST. Also, treatment differences in patterns of
      change in attempted suicide (caregiver report) varied as a function of ethnicity,
      gender, and age. Moreover, treatment effects were found for caregiver-rated
      parental control but not for youth depressive affect, hopelessness, or suicidal
      ideation. CONCLUSIONS: Results generally support MST's effectiveness at reducing
      attempted suicide in psychiatrically disturbed youngsters, whereas the effects of
      hospitalization varied based on informant and youth demographic characteristics.

PMID- 14726726
TI  - Differential effects of methylphenidate on attentional functions in children with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine the effects of methylphenidate on different attentional
      functions and behavior in children with attention-deficit/hyperactivity disorder
      (ADHD). METHOD: A total of 60 ADHD children aged between 8 and 12 years completed
      a randomized, double-blind, placebo-controlled, within-subject crossover trial
      with two doses of methylphenidate (0.25 and 0.5 mg/kg body weight) and placebo. A
      comprehensive neuropsychological test battery was applied, including tests of
      alertness and sustained, focused, and divided attention as well as two executive
      tests, the stop-signal paradigm and a visual set-shifting task. RESULTS: A linear
      improvement was identified for both medication conditions in the alertness and
      focused and sustained attention task, but no significant improvement was found
      for divided attention. Quadratic trends were found for both executive tasks.
      Responders defined by behavior ratings did not differ from nonresponders.
      CONCLUSIONS: Results indicate that attentional functions are influenced
      differentially by methylphenidate: intensity-dimension functions are best
      influenced by higher doses, executive functions by moderate doses, and
      selectivity-dimension functions by variable doses. In addition, divergent results
      from behavior rating scales and from attentional paradigms emphasize that
      clinicians have to decide what constitutes an appropriate clinical response. A
      more comprehensive assessment of attention may help to find an individually
      optimal dose for the treatment of attentional dysfunctions.

PMID- 14726727
TI  - Bupropion SR in adolescents with comorbid ADHD and nicotine dependence: a pilot
      study.
AB  - OBJECTIVE: Bupropion SR has been shown to be effective for the treatment of
      nicotine dependence in adults. This open-label pilot study was designed to
      examine the feasibility and preliminary tolerability of bupropion SR in
      adolescents with nicotine dependence. METHOD: Sixteen adolescents aged 12 to 19
      years were enrolled in the study. Eleven of the 16 participants also had comorbid
      attention-deficit/hyperactivity disorder (ADHD). Participants were titrated over
      1 week to bupropion SR 150 mg b.i.d. and maintained at this dosage for 6 weeks.
      Participants also received two brief smoking cessation counseling sessions.
      RESULTS: Nine participants received at least 4 weeks of medication. There was a
      significant decrease in the average number of cigarettes smoked (p <.00) and
      carbon monoxide levels (p =.04) over the course of treatment. Intent-to-treat
      analysis showed that 31.25% of the adolescents were completely abstinent (5/16)
      after 4 weeks of taking bupropion SR. Participants' weight did not change
      significantly during the study (p =.55). There was a no significant change in
      ADHD symptoms during the study (p =.1). CONCLUSIONS: Bupropion SR along with
      brief counseling may be safe and potentially efficacious for adolescents with
      nicotine dependence with and without ADHD. Smoking cessation trials in
      adolescents need to focus on strategies to increase retention for optimal effect.

PMID- 14726728
TI  - Tic reduction with risperidone versus pimozide in a randomized, double-blind,
      crossover trial.
AB  - OBJECTIVE: To compare the tic suppression, electrocardiogram (ECG) changes,
      weight gain, and side effect profiles of pimozide versus risperidone in children
      and adolescents with tic disorders. METHOD: This was a randomized, double-blind,
      crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17
      years with Tourette's or chronic motor tic disorder were randomized to 4 weeks of
      treatment with pimozide or risperidone, followed by the alternate treatment after
      a 2-week placebo washout. The primary efficacy outcome measure was change in tic
      severity assessed by the Yale Global Tic Severity Scale (YGTSS). ECG results,
      weight gain, and side effects were also compared. RESULTS: Compared to pimozide
      treatment, risperidone treatment was associated with significantly lower tic
      severity scores (YGTSS: baseline 43.3 +/- 17.5, pimozide 34.2 +/- 14.2,
      risperidone 25.2 +/- 13.6; p =.05). Weight gain during the 4-week treatment
      periods was greater for risperidone (mean 1.9 kg) than pimozide (1.0 kg). No
      patient suffered a serious adverse event, but 6 of 19 subjects failed to complete
      the protocol. Neither medication was associated with ECG changes. CONCLUSIONS: In
      this study, risperidone appeared superior to pimozide for tic suppression but was
      associated with greater weight gain.

PMID- 14726729
TI  - Elevated thyrotropin in bipolar youths prescribed both lithium and divalproex
      sodium.
AB  - OBJECTIVE: To examine the effect of combined lithium and divalproex sodium on
      thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar
      disorders and to identify risk factors for lithium-induced hypothyroidism.
      METHOD: Bipolar youths aged 5 to 17 years participating in an open-label clinical
      trial received treatment with lithium and divalproex sodium for up to 20 weeks.
      TSH levels were measured at baseline and at the end of the study. Subjects were
      divided into two groups for analysis: group 1 had TSH levels of less than 10.0
      mU/L at the end of the study and group 2 had TSH levels of 10.0 mU/L or more at
      end of the study. RESULTS: Twenty of the 82 subjects (24.4%) showed TSH
      elevations of at least 10 mU/L within an average exposure of less than 3 months.
      The mean baseline TSH level for group 2 was significantly higher than for group 1
      (2.97 [SD = 1.48] versus 2.05 [SD = 0.89], p <.05). Mean lithium levels at the
      end of the study were 1.00 mEq/L for group 2 compared to 0.76 mEq/L for group 1
      (t = -2.41, p =.019). CONCLUSIONS: Lithium is associated with significant rates
      of thyrotropin elevation in bipolar youths. Factors associated with elevation in
      TSH in lithium-treated subjects include a higher baseline TSH level and a higher
      lithium level. Close monitoring of thyroid function in children and adolescents
      taking lithium is recommended.

PMID- 14726730
TI  - Quality of life in children with psychiatric disorders: self-, parent, and
      clinician report.
AB  - OBJECTIVE: To study the relationship between child psychiatric disorders and
      quality of life (QoL). METHOD: In a sample of 310 children (ages 6-18 years)
      referred for psychiatric problems, children, parents, and clinicians reported on
      psychopathology and subjective and objective QoL indicators. RESULTS: Six
      diagnostic categories were distinguished: attention-deficit and disruptive
      behavior disorders, anxiety disorders, pervasive developmental disorders, mood
      disorders, other disorders, and no diagnosis. In overall QoL, no differences were
      found between the diagnostic categories, except in clinician's ratings, who rated
      children with pervasive developmental disorder as having a poorer QoL than
      children with other diagnoses. In each diagnostic category specific QoL
      subdomains were affected: for children with attention-deficit and disruptive
      behavior disorder, school functioning and social functioning; for children with
      anxiety disorder, emotional functioning; for children with pervasive
      developmental disorder, social functioning; and for children with mood disorder,
      emotional functioning. CONCLUSIONS: Across multiple raters, the distinguished
      child psychiatric disorders had a different impact on QoL. Knowledge about
      domains of QoL that are affected in specific child psychiatric disorders can help
      clinicians to focus on particular QoL domains during the diagnostic process and
      to define adequate treatment goals.

PMID- 14726731
TI  - Adolescent OxyContin Abuse.

PMID- 14726732
TI  - Creative expression workshops for immigrant and refugee children.

PMID- 14726733
TI  - Combination of surgery and intralesional verapamil injection in the treatment of
      the keloid.
AB  - Keloid scars are one of the most challenging problems for physicians and
      surgeons. These scars have been treated in many ways, with varying success.
      Verapamil is a widely used calcium channel antagonist, and it has been shown that
      calcium channel blockers inhibit the synthesis/secretion of extracellular matrix
      molecules, including collagen, glycosaminoglycans, and fibronectin, and increase
      collagenase. In this study, we performed total keloid excision in combination
      with reconstruction with W-plasty or skin grafting and injection of verapamil
      hydrochloride into the lesions of 21 patients with keloids. Patients were
      followed for minimum of 2 years, and the treatment outcome was evaluated based on
      the cosmetic appearances, symptomatic improvements, and the results of
      microscopic examinations. Also, patient satisfaction was scored with a visual
      analog scale. Two years after the operations, two patients had keloid in lesser
      diameter than the original lesions, two patients had lesions that were
      hypertrophic scars in appearance, and four patients had pruritus. One patient had
      keloid on the donor site. The rate of patient satisfaction was 6.4 on a scale of
      1 to 10. We reviewed the treatment of keloid in this study and obtained one of
      the lower rates of complication in the literature. We believe that surgical
      excision with W-plasty or skin grafting and intralesional verapamil injection may
      be a good alternative in the treatment of keloid.

PMID- 14726734
TI  - Burn pain and anxiety: the use of music relaxation during rehabilitation.
AB  - Pain and anxiety are well-documented problems during the rehabilitation of
      patients with burns. This study examined the effect of music on anxiety and pain
      during range of motion. Eleven subjects with partial-thickness or deeper burns
      were randomly assigned to a control group (without music intervention) or
      experimental group (with music intervention). Vital signs, pain, and anxiety were
      recorded before and after treatments. There was no difference in pretest and
      posttest anxiety across the groups; however, there was a difference in anxiety
      between the groups. Conversely, there was a difference in pretest and posttest
      pain across the groups but no difference in pain between the groups. Results
      showed no significant reduction in anxiety and pain during therapy with music
      relaxation. Limitations included nonhomogenous groups, small sample size,
      potentially unrepresentative sample, variation in exercise protocol, and small
      musical selection. Further research is recommended.

PMID- 14726735
TI  - The 2003 ABA presidential address: 9/11...this is not a drill!

PMID- 14726736
TI  - Visible vs hidden scars and their relation to body esteem.
AB  - This study examined the relationship among burn scarring, severity and
      visibility, and body esteem. Previous work addressing this question has relied on
      case studies and small samples. We mailed a survey to 2500 members of a national
      burn survivor support group. Survivors were asked to complete and return the
      mailed survey or complete the survey on line at our Web site. Three hundred sixty
      one survivors completed all questionnaires in the survey relevant to this study,
      which included measures of burn characteristics, social stigmatization, social
      support, depression, and body esteem. The sample characteristics were as follows:
      52% were women, the mean age was 44.1 years, the mean age burned was 26 years,
      88% were European American, 5% were African American, 4% were multiracial, 3%
      were other, the average TBSA was 48%, and the mean educational level was high
      school graduate. We measured scar visibility by asking survivors to rate "how
      often are your burn scars visible to others" on a six-point scale. We also asked
      them to rate the presence or absence of scars on 15 body parts, total TBSA, and
      number of surgeries. The correlation between visible scarring and different
      aspects of body esteem, that is, self-satisfaction with appearance (-.19) and
      perception of others reaction to your appearance (-.27), was statistically
      significant but low. Visible scarring was unrelated to self-satisfaction with
      weight (.01). Visible scarring had a low but significant correlation with
      perceived stigmatization (.23) and was not correlated with depression (0.01).
      Other measures of scarring also had low correlations with social and emotional
      outcome variables. Because scar severity and visibility are hypothesized to be
      particularly relevant to body esteem, we performed a multiple regression
      predicting body esteem. We entered the variables in three blocks: burn
      characteristics, demographic characteristics, and social and emotional
      characteristics. Burn characteristics accounted for less than 20% of the
      variance. R square for the final equation equaled.62, with social adjustment and
      depression accounting for the largest portion of the variance. In this sample,
      burn scar visibility and severity did not have a strong relationship with social
      and emotional adjustment variables. More effort must be placed into developing
      psychosocial interventions that help survivors accept scars, reduce depression,
      and build a strong loving support system.

PMID- 14726737
TI  - The 2003 Carl A Moyer Award: real-time metabolic monitors, ischemia-reperfusion,
      titration endpoints, and ultraprecise burn resuscitation.
AB  - Real-time metabolic monitoring of varied vascular beds provides the raw data
      necessary to conduct ultraprecise burn shock resuscitation based on second-by
      second assessment of regional tissue perfusion. It also illustrates shortcomings
      of current clinical practices. Arterial base deficit was continuously monitored
      during 11 clinical resuscitations of patients suffering burn shock using a
      Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three
      Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of
      the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8
      ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported
      laser Doppler images of actual burn wound capillary perfusion. With current
      clinical therapy, continuous monitoring of arterial base deficit revealed
      repetitive cycles of resolution/worsening/resolution during burn shock
      resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic
      circulation differed depending on the rate of fluid resuscitation (P <.01 between
      sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound
      pCO2 values correlated well with laser Doppler determination of actual capillary
      perfusion (rho = -.48, P <.01). The following conclusions were reached: 1).
      Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current
      clinical therapy as demonstrated by numerous "false starts" in the resolution of
      arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and
      splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid
      administration; and 3). burn wound and splanchnic pCO2 are highly correlated with
      direct measurement of burn wound capillary perfusion by laser Doppler imager.
      Either technique can serve as a resuscitation endpoint for real-time feedback
      controlled ultraprecise resuscitation.

PMID- 14726738
TI  - The 2003 Everett Idris Evans memorial lecture: every cloud has a silver lining.

PMID- 14726739
TI  - Digital photography: enhancing communication between burn therapists and nurses.
AB  - Burn rehabilitation therapists rely on nursing staff to follow through with the
      positioning and splinting programs. To communicate more effectively, a
      communication tool that consisted of digital photos and written instructions was
      created. Microsoft Word and Nikon View software were used to design the
      communication tool. The purpose of the study was to assess the perceived
      effectiveness of a communication tool between burn therapists and burn nurses for
      splinting and positioning. Thirty-two surveys were distributed to burn nursing
      staff to assess their perception of the communication tool (digital photographs
      with written instructions) compared with previous methods of instructions
      (without digital photographs). Seventy-three percent of nurses felt the
      communication tool with verbal instructions were the best methods of
      communicating splinting and positioning needs. All respondents felt that the
      rehabilitation staff should continue to use the communication tool.

PMID- 14726740
TI  - Self-reported quality of life after electrical and thermal injury.
AB  - Electrical injury patients (EI) often require more procedures and longer hospital
      stays than their thermal injury counterparts. We hypothesized that postinjury
      quality of life might be better in thermal injury patients (TIs) than in EI. Each
      EI recorded in our institution's TRACS trade mark /ABA registry between 1995 and
      2000 was matched with a TI for age and TBSA involvement. We compared SF-36 scores
      of EI and TIs to evaluate quality of life. Age and TBSA injury were similar
      between groups. SF-36 results demonstrated no significant differences in self
      reported quality of life indices. Return to full-time employment did not differ
      significantly between groups. EI and TIs do not differ significantly in quality
      of life after their burn injuries. Self-evaluated function for EI and TIs is
      comparable. Quality of life in both EI and TIs are above population means on many
      dimensions.

PMID- 14726741
TI  - Contact palm burns in toddlers from glass enclosed fireplaces.
AB  - We have seen an alarming increase in the incidence of pediatric palm burns
      associated with gas fireplaces. The increasing popularity of these units places
      more children at risk. Medical records of patients under the age of 5 years who
      sustained hand burns from contact with the glass enclosure of gas fireplaces from
      1996 through 2002 were reviewed. Thirty-nine patients were identified, with a
      mean age of 12.8 months. A 15-fold increase in incidence was observed. Thirty
      three patients suffered superficial second-degree burns that were treated
      conservatively. Twenty-one percent of children developed significant wound
      complications requiring intensive therapy including extension splinting or
      surgery. Pediatric burns resulting from palmar contact with the glass enclosures
      of gas fireplaces have emerged as an avoidable new danger within the home.
      Although most of these injuries heal with conservative treatment alone, many
      require surgery or other intensive management to regain acceptable function.

PMID- 14726742
TI  - Blood transfusion in burns: what do we do?
AB  - Over 11 million units of blood are transfused yearly in the United States.
      Although blood transfusion is common in burns, data are lacking on appropriate
      transfusion thresholds. The purpose of the study was to identify current burn
      center physician blood transfusion practices. A 30-question survey of blood
      transfusion practices was developed and sent to burn center directors. The survey
      assessed demographics, burn experience, and blood transfusion thresholds.
      Physicians were asked to list factors affecting their blood transfusion
      thresholds and then to give their blood transfusion threshold for patients based
      on age and percent burn. The final section presents three case scenarios with
      alterations in one physiological parameter to assess the effect on transfusion
      thresholds. A total of 55 of the 180 surveys (31%) were returned. Mean number of
      burn beds was 15.7 +/- 1.4, with 264 +/- 25 burn admissions per year. The
      respondents had been in burn care for 15.9 +/- 1.4 years. Their mean hemoglobin
      transfusion threshold was 8.12 +/- 1.7 g/dl. The most frequent reasons for
      transfusion were ongoing blood loss (22%), anemia (20%), hypoxia (13%), and
      cardiac disease (12%). Inhalation injury influenced the decision to transfuse
      blood in 34%. The hemoglobin level below which respondents would transfuse blood
      increased with increasing TBSA burn, history of cardiac disease, acute
      respiratory distress syndrome, and age. Blood transfusion thresholds in burns
      vary based on burn percentage, age, and presence of cardiac disease. To date, no
      standard of care exists for blood transfusions in burns. Future prospective
      studies are needed to determine the appropriate use of blood in burns.

PMID- 14726743
TI  - Procalcitonin in pediatric burn patients: an early indicator of sepsis?
AB  - To determine whether changes in procalcitonin (PCT) could be used to predict the
      onset of sepsis, daily PCT levels were monitored in 20 burned children. Analysis
      indicated a PCT rise of 5 ng/ml or greater as the best indication of sepsis. We
      compared the surgeons' determination of sepsis, which was based on changes in
      platelet count, C-reactive protein (CRP), and other clinical manifestations, with
      the prediction of sepsis from PCT. There were 26 septic episodes and 36 nonseptic
      episodes in the 20 patients. PCT results were classified as to true positives,
      false positives, true negatives, and false negatives. As an indicator of sepsis,
      the PCT assay had a sensitivity of 42%, a specificity of 67%, and an efficiency
      of 57%. Even when the assay correctly identified sepsis, the determination was
      made an average of 0.8 days after the surgeon had already made the diagnosis
      based on CRP and/or platelet count. We conclude that PCT is not as effective as
      CRP and/or platelet count in the early detection of sepsis in burned children.

PMID- 14726744
TI  - Toxic epidermal necrolysis: does immunoglobulin make a difference?
AB  - Experimental evidence implicates Fas ligand-mediated keratinocyte apoptosis as an
      underlying mechanism of toxic epidermal necrolysis syndrome (TEN). In vitro
      studies indicate a potential role for immunoglobulin (Ig) therapy in blocking Fas
      ligand signaling, thus reducing the severity of TEN. Anecdotal reports have
      described successful treatment of TEN patients with Ig; however, no study to date
      has analyzed outcome data in a large series of patients treated with Ig using
      institutional controls. The SCORTEN severity-of-illness score ranks severity and
      predicts prognosis in TEN patients using age, heart rate, TBSA slough, history of
      malignancy, and admission blood urea nitrogen, serum bicarbonate, and glucose
      levels. A retrospective chart review was performed that included all patients
      treated for TEN at our burn center since 1997. Ig therapy was instituted for all
      patients with biopsy-proven TEN beginning in January 2000. Twenty-one TEN
      patients were treated before Ig (no-Ig group), and 24 patients have been treated
      with Ig. SCORTEN data were collected, as well as length of stay (LOS) and status
      upon discharge. Each patient was given a SCORTEN of 0 to 6, with 1 point each for
      age greater than 40, TBSA slough greater than 10%, history of malignancy,
      admission BUN greater than 28 mg/dl, HCO3 less than 20 mg/dl, and glucose greater
      then 252 mg/dl. Outcome was compared between patients treated with Ig and without
      Ig. Overall mortality for patients treated before Ig was 28.6% (6/21), and with
      Ig, mortality was 41.7%% (10/24). There was no significant difference in age or
      TBSA slough. The average SCORTEN between the groups was equivalent (2.2 in no-Ig
      group vs 2.7 in Ig group, P = 0.3), and no group of patients with any SCORTEN
      score showed a significant benefit from Ig therapy. Overall LOS as well as LOS
      for survivors was longer in the Ig group. This series represents the largest
      single-institution analysis of TEN patient outcome after institution of Ig
      therapy. Our data do not show a significant improvement in mortality for TEN
      patients treated with Ig at any level of severity and may indicate a potential
      detriment in using Ig. Ig should not be given to TEN patients outside of a
      clinical trial. A multicenter, prospective, double-blinded randomized trial is
      necessary and urgently indicated to determine whether Ig therapy is beneficial or
      harmful in the care of TEN patients.

PMID- 14726745
TI  - Aquacel Ag in the management of partial-thickness burns: results of a clinical
      trial.
AB  - Aquacel Hydrofiber is a moisture retentive topical dressing that has been
      demonstrated to be safe and efficacious for the management of partial-thickness
      burns, showing parity for most dressing related aspects to cadaver skin for this
      indication. Recently, 1.2% w/w silver has been added to the Aquacel Hydrofiber,
      to create Aquacel Ag. This new material releases silver within the dressing for
      up to two weeks, and it is this duration that differentiates it from other
      sustained release silver delivery products indicated for burn management. The
      dressing was tested in a phase II noncomparative trial in superficial, mid
      dermal, and mixed partial-thickness burns. Percentage and speed of
      reepithelialization were satisfactory and appear to be similar at least to
      results noted with silver sulfadiazine, although, no direct comparisons were
      performed in this study. Pain reduction between baseline and postburn day number
      three and five was statistically significant. Conformability, general ease of use
      and other functional dressing properties were rated very positively. Overall,
      Aquacel Ag combines several properties known to be beneficial for the management
      of partial-thickness burns and is a very good choice for superficial and mid
      thickness burn injuries.

PMID- 14726746
TI  - Psychological problems reported by young adults who were burned as children.
AB  - This study assessed long-term psychosocial sequelae of young adult pediatric burn
      survivors. Subjects were 101 young adults (43 females and 58 males) between the
      ages of 18 and 28 years who were at least 2 years (average, 14 years) postburn at
      least 30% TBSA (mean = 54 +/- 20%). Educational status was 25% high school
      dropouts, 28% high school graduation only, 32% some college, and 5% completed
      college. Seventy-seven percent either worked or attended school; 28% had had a
      long-term partner. When assessed by Achenbach's Young Adult Self-Report (YASR)
      scale and compared with its published reference group, the males reported
      differences only in the somatic complaints, but the females endorsed
      significantly more externalizing and total problems, specifically withdrawn
      behaviors, somatic complaints, thought problems, aggressive behavior, and
      delinquent behavior. Despite these problems suffered by some female pediatric
      burn survivors, the overall outcome revealed that most pediatric burn survivors
      are making the transition into adulthood with minimal unexpected difficulty.

PMID- 14726747
TI  - Burn injury in patients with early-onset neurological impairments: 2002 ABA
      paper.
AB  - Many patients suffer from sensorimotor deficits that may contribute to burn
      injury. This retrospective study examines burn injuries in the subgroup of
      patients that suffer from the early onset neurological impairments of mental
      retardation, cerebral palsy, spina bifida, autism, and attention deficit
      hyperactivity disorder. Fifty-one patients who suffered from the above-mentioned
      early-onset neurological impairments were admitted to our burn center during a 4
      year period. The average TBSA burned was 8.9% yet resulted in prolonged
      hospitalizations. This study describes our burn center's experience in treating
      patients admitted with early-onset neurological impairments.

PMID- 14726748
TI  - Insulin-like growth factor-I blocks dexamethasone-induced protein degradation in
      cultured myotubes by inhibiting multiple proteolytic pathways: 2002 ABA paper.
AB  - In previous studies, insulin-like growth factor-I (IGF-I) inhibited
      glucocorticoid-induced muscle protein breakdown, but the intracellular mechanisms
      of this effect of IGF-I are not well understood. The purpose of the present study
      was to test the hypothesis that IGF-I inhibits multiple proteolytic pathways in
      dexamethasone-treated cultured L6 myotubes. Myotubes were treated with 1 microM
      dexamethasone for 6 hours in the absence or presence of 0.1 microg/ml of IGF-I.
      Protein degradation was determined by measuring the release of trichloroacetic
      acid-soluble radioactivity from proteins prelabeled with 3H-tyrosine. The
      contribution of lysosomal, proteasomal-dependent, and calpain-dependent
      proteolysis to the inhibitory effect of IGF-I on protein degradation was assessed
      by using inhibitors of the individual proteolytic pathways (methylamine, beta
      lactone, and E64, respectively). In addition, the influence of IGF-I on cathepsin
      B, proteasome, and calpain activities was determined. Treatment of L6 myotubes
      with dexamethasone resulted in an approximately 20% increase in protein
      degradation. This effect of dexamethasone was completely blocked by IGF-I. When
      the different protease inhibitors were used, results showed that IGF-I inhibited
      lysosomal, proteasomal-dependent, and calpain-dependent proteolysis by 70, 44,
      and 41%, respectively. Additionally, IGF-I blocked the dexamethasone-induced
      increase in cathepsin B, proteasome, and calpain activities. The present results
      suggest that IGF-I inhibits glucocorticoid-induced muscle proteolysis by blocking
      multiple proteolytic pathways.

PMID- 14726750
TI  - Burns as a complication of the use of diathermy.
AB  - Surgical diathermy is an invaluable aid in modern surgery, and most contemporary
      diathermy machines are considered safe. The literature has proven to be very
      sparse in terms of reference to complications, although prolonged courses of
      treatment are required in individual cases. We report a case of burns that
      occurred during a saphenous vein coronary bypass graft caused by the inadequate
      use of the electrosurgical materials. Care should be taken in the use of these
      resources to avoid complications of this kind.

PMID- 14726751
TI  - The circle of safety: a campfire burn prevention campaign expanding nationwide.
AB  - Camping is a popular family activity, especially during the spring and summer
      months. Campfires are a common activity among campers. They offer a source of
      recreation but also pose a risk for severe burns. The rising number of children
      with campfire burns seen at our institution triggered a quest for a campaign for
      the prevention of these injuries. A chart review was performed to study the
      characteristics and the circumstances of burn injuries of all children treated
      for campfire-related injuries over a 4-year period between 1997 and 2001. Thirty
      two children sustained campfire-related burn injuries, with 88% being under the
      age of 7. The children had either fallen into the campfire or walked into
      simmering coals. All accidents would have been prevented if the children had kept
      a safe distance from the campfire. Normal growth charts were used to determine
      the average height of 7-year-old children as being 48 inches. A campaign was
      started to encourage families to keep a safe distance of 4 feet from their
      campfires by drawing a "circle of safety" with a stick on the ground 4 feet away
      from the fire.

PMID- 14726753
TI  - Management of postburn recalcitrant knee ulcers in pediatric patients.
AB  - The sequelae of severe lower-extremity burn injuries in children include
      ulcerations and unstable scars of the anterior knee. Although the weight-bearing
      and ambulatory demands on this joint predispose the ulcers to chronicity,
      recalcitrance to treatment in the absence of systemic factors may be indicative
      of the presence of less-than-optimal local factors mitigating against healing. In
      our experience, excessive skin tightness around the knee joint has played a key
      role in this respect. This retrospective study on 10 patients with 16
      recalcitrant knee ulcers demonstrated the inadequacy of the traditional treatment
      approach of ulcer excision and grafting. However, incisional release of tight
      skin above the knee joint and resurfacing the defect with split-thickness skin
      graft (mean size, 118.26 +/- 35.32 cm2) eliminated excessive tension and allowed
      the ulcers to heal spontaneously and permanently. We found this approach useful
      in select patients, and we are favorably disposed to additional releasing
      incision and grafting if the need arises in the growing child.

PMID- 14726754
TI  - Effective hand function assessment after burn injuries.
AB  - This study compared two methods of hand function assessment, the Michigan Hand
      Outcomes Questionnaire (MHQ) and the Test d'Evaluation des Membres Superieurs des
      Personnes Agees (TEMPA) in 20 patients discharged from a regional adult burn
      center (1995-1999). Spearman's rank correlation coefficient analysis was used to
      compare the MHQ and TEMPA scores, with P <.05 considered significant. The MHQ
      revealed that 68% of patients reported hand function deterioration, mainly with
      the nondominant hand (65%). Activities of daily living (76%) and work (59%) were
      the most affected. According to the MHQ, patient satisfaction correlated with
      work performance (r =.66, P =.002), aesthetics (r =.64, P =.003), pain (r =.59, P
      =.008), and activities of daily living (r =.54, P =.017). The MHQ indicated more
      hand function deterioration than the TEMPA. There was a significant correlation
      between the MHQ and TEMPA total scores (r =.68, P =.001). This study supports
      using the MHQ to determine which patients would benefit from the more resource
      consuming TEMPA.

PMID- 14726756
TI  - Shedding the layers: exploring the impact of the burn camp experience on
      adolescent campers' body image.
AB  - The purpose of this qualitative study was to explore the impact of the burn camp
      experience, as it relates to body image, on participating burn-injured
      adolescents. Focus groups were conducted with 52 burn-injured adolescents at
      three burn camps in geographically diverse regions of the United States. Data
      revealed that burn camp is a place where these adolescents feel a sense of
      belonging and acceptance, a place where they don't have to hide their bodies, and
      a place where they can learn to integrate their scars into their overall body
      image in a positive way. Implications of this study include highlighting the
      contributions that burn camps may provide in helping burn-injured adolescents
      learn to cope with the devastating disfigurements that often accompany their
      injuries.

PMID- 14726757
TI  - Regulatory T cells finally get the attention they deserve.

PMID- 14726758
TI  - Proceedings of the Third Beaune Seminar in Transplant Research. May 15-16, 2003.
      Hotel-Dieu Beaune, France.

PMID- 14726759
TI  - Regulatory (suppressor) T cells in peripheral allograft tolerance and graft
      versus-host reaction.
AB  - Among the mechanisms capable of inducing peripheral tolerance, regulatory
      (suppressor) T cells (Treg) probably play a key role in the control of both
      reactivity to self-antigens and alloimmune response. Augmentation or manipulation
      of Treg could improve organ allograft survival or control graft-versus-host
      disease, thus resulting in operational tolerance. The role of this
      immunomanipulation as one method of inducing tolerance has yet to be clearly
      defined.

PMID- 14726760
TI  - Regulatory T cells: potential in organ transplantation.
AB  - Active regulation or suppression of donor reactive cells is emerging as a key
      mechanism for inducing and maintaining unresponsiveness to donor alloantigens.
      Accumulating evidence suggests that a balance between immunoregulation and
      deletion of donor alloantigen reactive T cells can provide effective control of
      immune responsiveness after organ or cell transplantation. In many settings,
      immunoregulatory activity is enriched in CD4+ T cells that express high levels of
      CD25, and common mechanisms appear to be responsible for the activity of
      regulatory T cells in both transplantation and the control of reactivity to self
      antigens.

PMID- 14726761
TI  - Suppression of graft-versus-host disease by naturally occurring regulatory T
      cells.
AB  - Studies of graft-versus-host disease after allogeneic bone marrow transplantation
      have shown that there are subsets of freshly isolated donor T cells that induce
      the disease and subsets that suppress the disease. The balance of subsets in the
      graft determines disease severity. The authors' work on the nature of the
      regulatory-suppressor T cells and their mechanisms of action is summarized in
      this article.

PMID- 14726762
TI  - Specialization in tolerance: innate CD(4+)CD(25+) versus acquired TR1 and TH3
      regulatory T cells.
AB  - The regulation of immune responses to self-antigens is a complex process that
      involves maintaining self-tolerance while retaining the capacity to mount robust
      immune responses against invading microorganisms. Over the past few years, many
      new insights into this process have been gained, leading to the reemergence of
      the idea that regulatory T cells (Treg) are key players in immune regulation.
      These insights have raised fundamental questions concerning the definition of a
      Treg and what exactly constitutes T-cell-mediated suppression, identification of
      the signals and the cellular environment that promote the development and
      differentiation of these cells, and which signals maintain the homeostasis of the
      immune system. Thus far, the different models where Treg have been characterized
      cannot fully account for CD(4+)CD(25+) T cells. In this article, the authors
      propose the coexistence of two specialized types of CD(4+) Treg-innate and
      acquired-that differ in terms of their development, specificity, mechanisms, and
      sites of action.

PMID- 14726763
TI  - The role of cytokines (and not only) in inducing and expanding T regulatory type
      1 cells.
AB  - T regulatory (Tr) type 1 cells are one of the most studied of CD4+ Tr cell
      subsets. They are distinct from other T-cell subsets in their cytokine production
      profile and in their ability to suppress immune responses both in vitro and in
      vivo. Human and murine Tr1 cells share many properties, but signals regarding
      their in vitro induction are different. Although culture of murine naive CD4+
      cells in the presence of high doses of interleukin (IL)-10 is sufficient for Tr1
      induction, human naive CD4+ T cells can give rise to Tr1 cells when cultured with
      IL-10 and interferon-alpha. Tr1 cells can also be induced in vivo, although the
      mere administration of IL-10 is not sufficient to generate Tr1 cells in a context
      of murine allogenic transplant. IL-10 needs to be combined with immunosuppressive
      compounds, which are permissive for tolerance induction, to generate or expand
      Tr1 cells in vivo and mediate antigen-specific tolerance. Whether this combined
      treatment can also be used in humans is still an open question.

PMID- 14726764
TI  - The cytotoxic potential of regulatory T cells: what has been learned from gene
      knockout model systems?
AB  - The mechanisms of T-cell regulation are difficult to elucidate because of their
      complexity and the numerous subcategories of cell populations. There are two
      fundamental approaches to address this conundrum. First, it is possible to use a
      purified cell population and submit these cells to various assays. The second
      approach is to manipulate a target molecule and determine what effect this has on
      T-cell homeostasis in vitro and in vivo. This molecular strategy may help
      characterize multiple regulatory populations that use the same pathway for
      controlling T-cell function. Through a concerted two-pronged effort, the authors'
      laboratory and others have attempted to decipher different molecular pathways for
      regulatory cell function. Several gene knockout mouse models display a phenotype
      of profound lack of homeostasis in which T cells accumulate, presumably because
      of a defect in regulation. Dependent on the molecule disrupted, the immune cell
      subset being examined may no longer be appropriately regulated. Accordingly, the
      phenotype of exogenously added "putative" regulatory cells can then be examined
      by assessing their ability to control this aberrant accumulation. By using co
      transplantation techniques, much information can be postulated regarding
      potential regulatory cell phenotype and function. Model systems with target gene
      manipulations involving Fas ligand, Fas, perforin, interleukin-2, and cytotoxic T
      lymphocyte-associated antigen-4 exist and in all cases appear to disrupt critical
      cytotoxic regulatory cell function.

PMID- 14726765
TI  - Human CD(4+)CD(25+) regulatory T cells and infectious tolerance.
AB  - Control of autoaggressive T cells by regulatory T cells (Treg) is essential to
      ensuring peripheral tolerance. Several subsets of CD(4+) T cells with suppressive
      properties have been described, including induced T helper (Th) type 3 and T
      regulatory (Tr) type 1 cells and naturally occurring CD(4+)CD(25+) Treg.
      CD(4+)CD(25+) Treg suppress the response of conventional T cells in a cell
      contact-dependent manner, whereas Th3 and Tr1 cells produce immunosuppressive
      cytokines. Two subsets of human CD(4+)CD(25+) Treg, characterized by expression
      of the integrins alpha4beta7 or alpha4beta1, are able to convey suppressive
      capacity to conventional CD(4+) T cells, thereby generating Th suppressor cells
      (Th(sup)). One outstanding feature is the generation of Th(sup) with distinct
      properties. alpha4beta7 Treg induce Tr1-like interleukin (IL)-10-producing
      Th(sup), whereas alpha4beta1 Treg induce Th3-like Th(sup), which produce
      transforming growth factor (TGF)-beta. Thus, our findings reconcile contradictory
      results clearly demonstrating that suppression is contact dependent in vitro but
      mediated by soluble factors (IL-10 and TGF-beta) in vivo.

PMID- 14726766
TI  - Pretransplant blood transfusions revisited: a role for CD(4+) regulatory T cells?
AB  - Pretransplant blood transfusions have been shown to improve organ allograft
      survival. However, the immunologic mechanism leading to this beneficial effect of
      blood transfusions is still unknown. The observation that transfusions sharing at
      least one HLA-DR antigen (human leukocyte antigen) with the recipient are more
      effective than HLA-mismatched transfusions has led to the hypothesis that CD(4+)
      regulatory T cells are induced that recognize allopeptides of the blood
      transfusion donor in the context of the self-HLA-DR molecule on the donor cells.
      In vitro studies showed that CD(4+) T cells recognizing an allopeptide in the
      context of self-HLA-DR are indeed able to decrease the alloimmune response of
      autologous T cells by affecting the activated T cells directly or indirectly by
      their modulatory effect on dendritic cells. The first studies in a patient with a
      well-functioning kidney graft after receiving an HLA-DR-matched pretransplant
      blood transfusion showed that the low organ donor-specific cytotoxic T-lymphocyte
      response after transplantation was indeed attributable to the activity of
      regulatory CD(4+) T cells.

PMID- 14726767
TI  - Ultraviolet light-induced regulatory (suppressor) T cells: an approach for
      promoting induction of operational allograft tolerance?
AB  - Ultraviolet (UV) light is known to induce skin cancers by causing DNA gene
      mutations and inducing immunosuppression. Taking advantage of these
      immunosuppressive capacities, UV light has been used, with different modalities,
      as an immunosuppressive therapy in a variety of diseases including allograft
      rejection and graft-versus-host disease. Phototherapy includes UVB irradiation,
      UVA irradiation, oral psoralen (+)UVA irradiation (PUVA), photodynamic therapy,
      and extracorporeal photopheresis, which consists of infusion of UVA-irradiated
      autologous leukocytes collected by apheresis and incubated with 8
      methoxypsoralen. According to numerous experimental models and human data, there
      is increasing evidence that UVB irradiation and extracorporeal photopheresis can
      induce regulatory T cells and anticlonotypic activity. These therapies induce
      apoptosis of activated T cells or of extracorporally treated mononuclear cells,
      and up-regulate the expression of costimulary molecules and adhesion molecules on
      antigen presenting cells. UVB- or UVA-induced apoptotic cells could secrete
      immune suppressive cytokines (interleukin (IL)-4, IL-10). The processing and
      presentation of apoptotic T cell antigens from clones of pathogenic T cells by
      activated antigen presenting cells might explain the induction of systemic
      anticlonotypic activity by photopheresis. This induction of cell-mediated
      suppressive activity opens up future prospects with the aim of expanding
      regulatory T cells and/or anticlonotypic activity, especially by photopheresis in
      organ and cell transplantation.

PMID- 14726769
TI  - Potential role of major histocompatibility complex class II peptides in
      regulatory tolerance to vascularized grafts.
AB  - The inactivation of persisting T lymphocytes reactive to self- and non-self
      antigens is a major arm of operational immune tolerance in mammals. Silencing of
      such T cells proceeds mostly by means of suppression, a process that is mediated
      by regulatory T-cell subsets and especially by CD4(+)CD(25high) regulatory T
      cells (Treg). Although Treg activation and ensuing suppressive activity appear to
      be major histocompatibility complex class II dependent, the fine specificity of
      Treg T-cell receptors has not yet been elucidated. Recent data from the author's
      laboratory on a class II gene therapy induction of tolerance to allogeneic kidney
      grafts suggest that class II peptides are involved as generic signals for Treg
      activation. A brief compilation of results that would support this hypothesis is
      discussed in the present article.

PMID- 14726768
TI  - Ex vivo selection of recipient-type alloantigen-specific CD4(+)CD25(+)
      immunoregulatory T cells for the control of graft-versus-host disease after
      allogeneic hematopoietic stem-cell transplantation.
AB  - Allogeneic hematopoietic stem-cell transplantation (HSCT) is the treatment of
      choice for many malignant and nonmalignant hematologic disorders. Donor T cells
      present in the hematopoietic stem-cell transplant improve engraftment and immune
      reconstitution and contribute to the graft-versus-leukemia effect, but are also
      responsible for the life-threatening graft-versus-host disease (GVHD).
      CD4(+)CD25(+) immunoregulatory T cells, which play a pivotal role in preventing
      organ-specific diseases, can also modulate GVHD if administered in equal numbers
      of T cells at the time of grafting. In this article, the authors describe a
      procedure of ex vivo selection and expansion of regulatory T cells specific for
      recipient-type alloantigens. These expanded regulatory T cells controlled GVHD.
      Their therapeutic use in HSCT should allow specific suppression of the activation
      of donor alloreactive T cells involved in GVHD while preserving the beneficial
      effects of other T cells.

PMID- 14726770
TI  - Immune regulation and transplantation: an exciting challenge.

PMID- 14726771
TI  - The pain experience of children with leukemia during the first year after
      diagnosis.
AB  - BACKGROUND: Children with cancer experience pain related to the disease process,
      the treatment, and the associated procedures. For children with leukemia, the
      pain experienced after diagnosis has received scant attention. OBJECTIVE: To
      examine the pain experience, management strategies, and outcomes during the first
      year after the diagnosis of acute leukemia. METHODS: A longitudinal descriptive
      approach was used to collect data at seven data points from 95 English- and
      Spanish-speaking children, ages 4 to 17 years, receiving care in one of three
      southern California hospitals, and from their English- and Spanish-speaking
      parents. Age-appropriate instruments were used to examine the variables of pain
      intensity, location, pattern over time, and quality, as well as strategies for
      managing pain, perceived effectiveness of management strategies, and functional
      status. RESULTS: All the children reported pain over the course of the year. Pain
      intensity scores incorporated the full range of possible responses. For the
      children 4 to 7 years old, the highest and lowest mean scores, respectively, were
      2 and 1.6 (scale, 0-4). For the children 8 to 17 years old, the highest and
      lowest mean scores, respectively, were 50.1 and 39.5 (scale, 0-100). The most
      common location of pain was the legs (26.5%) in all seven interviews. Other
      frequently noted sites were the abdomen (16.6%), head/neck (16.6%), and back
      (14.2%). The words used most frequently by the older English- and Spanish
      speaking children to describe pain were "uncomfortable" (incomodo) and "annoying"
      (molesto). According to the interviews, the most frequently used strategy for
      pain management was stressor modification (e.g., medication, sleep, hot/cold, and
      massage). The most common coping strategies according to a Likert scale rating
      were "watch TV" (n = 426), "lie down" (n = 421), "wish for it to go away" (n =
      417), and "tell my mother or father" (n = 416). The pain intensity scores after
      pain management were significantly lower for the younger children in three of the
      seven interviews and for the older children in all seven interviews. For both the
      younger and older children, functional status (i.e., the ability to engage in
      routine activities) was above the median score at the seven interviews.
      CONCLUSIONS: Children with leukemia experience pain throughout the first year of
      treatment. In this study, the pain was responsive to the management strategies
      used by the parents and children.

PMID- 14726772
TI  - Critical thinking, perceived health status, and participation in health
      behaviors.
AB  - BACKGROUND: Critical thinking has been proposed as crucial for processing
      conflicting information when people make decisions about participation in health
      behaviors. The critical thinking of individuals about participation in health
      behaviors may depend on their perceived health status. OBJECTIVES: To examine the
      relations between critical thinking and participation in three categories of
      health behaviors, and to determine whether these relations are moderated by
      perceived health status. METHODS: A cross-sectional, correlational design was
      used to study a sample of 112 community-dwelling adults who resided in a large,
      urban Midwest community. The participants were women and men 18 to 90 years of
      age (mean, 55 +/- 20.47 years) who completed self-report, written questionnaires
      including the Test of Everyday Reasoning and the Health Practices Instrument.
      RESULTS: According to hierarchical multiple regression analyses, the relation
      between critical thinking and health promotion behaviors and the relation between
      critical thinking and secondary prevention behaviors were moderated by perceived
      health status, whereas the relation between critical thinking and health
      protection behaviors was not. CONCLUSIONS: The relation between critical thinking
      and participation in health behaviors depends on perceived health status and
      category of health behaviors. Researchers can explore the role of other variables
      (e.g., functional status and perceived susceptibility to disease) to explain why
      perceived health status moderates the relations between critical thinking and
      participation in various types of health behaviors differently.

PMID- 14726773
TI  - The Chinese version of the PSS:PICU.
AB  - BACKGROUND: Before an established research instrument is adopted for use in a
      cultural context different from that where it was developed, its validity and
      reliability must be reassessed so that it is applicable to and congruent with the
      culture of the population under study. OBJECTIVES: To translate the Parental
      Stressor Scale: Pediatric Intensive Care Unit (PSS:PICU) into Chinese, and to
      evaluate the psychometric properties of the Chinese version. METHODS: A
      prospective study investigated 81 parents of 75 children admitted to a PICU in
      two hospitals. Parents completed the Chinese versions of the PSS:PICU and the
      state anxiety scale of the Spielberger State-Trait Anxiety Inventory. RESULTS:
      Factor analysis and item-subscale correlations supported the conceptual
      dimensions of the original instrument. The internal consistency of the Chinese
      version was high. Most of the subscales were moderately correlated with each
      other and strongly correlated with the total score. The convergent validity with
      the state anxiety scale in the Chinese version of the Spielberger State-Trait
      Anxiety Inventory was reflected by a weak correlation for the overall scale and
      for the subscales. CONCLUSIONS: Although some satisfactory psychometric
      properties of the translated instrument were found in this study, they should be
      used as a reference for studies with larger samples. The current form is not
      ready for wide dissemination until more concrete research evidence is available.

PMID- 14726774
TI  - Birth trauma: in the eye of the beholder.
AB  - BACKGROUND: The reported prevalence of posttraumatic stress disorder after
      childbirth ranges from 1.5% to 6%. OBJECTIVE: To describe the meaning of women's
      birth trauma experiences. METHODS: Descriptive phenomenology was the qualitative
      research design used to investigate mothers' experiences of traumatic births.
      Women were recruited through the Internet, primarily through Trauma and Birth
      Stress (TABS), a charitable trust located in New Zealand. The purposive sample
      consisted of 40 mothers: 23 in New Zealand, 8 in the United States, 6 in
      Australia, and 3 in the United Kingdom. Each woman was asked to describe the
      experience of her traumatic birth and to send it over the Internet to the
      researcher. Colaizzi's method was used to analyze the 40 mothers' stories.
      RESULTS: Four themes emerged that described the essence of women's experiences of
      birth trauma: To care for me: Was that too much too ask? To communicate with me:
      Why was this neglected? To provide safe care: You betrayed my trust and I felt
      powerless, and The end justifies the means: At whose expense? At what price?
      CONCLUSIONS: Birth trauma lies in the eye of the beholder. Mothers perceived that
      their traumatic births often were viewed as routine by clinicians.

PMID- 14726775
TI  - Health behaviors as mediators for the effect of partner abuse on infant birth
      weight.
AB  - BACKGROUND: Intimate partner abuse of pregnant women has been linked to the
      delivery of low-birth-weight infants. Also, abused pregnant women have reported a
      greater prevalence of substance abuse, poor nutrition, and demographic risk
      factors for poor birth outcomes. These factors may play a role in the reported
      relation between intimate partner violence and birth weight. OBJECTIVES: To
      explore the role of substance abuse (smoking, alcohol, and drug use) and weight
      gain of less than 15 pounds during pregnancy as potential mediators of the
      relation between recent partner abuse and infant birth weight, and to investigate
      the role of demographic risk factors as potential moderators for the impact of
      abuse on birth weight. METHODS: Data were extracted on abuse screening results,
      demographics, birth outcomes, and a range of medical and obstetric risks and
      complications from the medical records of 1969 women who had been screened by
      clinicians for domestic abuse during pregnancy. Hypotheses were tested using
      multiple regression analysis. RESULTS: Recent physical or psychological abuse had
      a small but significant effect on birth weight in this sample. Smoking and low
      weight gain were weak but significant mediators of the relation between recent
      abuse and infant birth weight. Single marital status was the strongest
      demographic predictor of decreased birth weight. No moderator effects were found.
      CONCLUSIONS: Although prospective studies are warranted, nursing care to reduce
      smoking and promote adequate weight gain in all women along with support for
      women's efforts to seek safety from abuse may help to improve birth outcomes and
      promote maternal well-being.

PMID- 14726776
TI  - Presurgical risk factors for late extubation in Medicare recipients after cardiac
      surgery.
AB  - BACKGROUND: Medicare recipients, particularly those 80 years of age and older,
      are increasingly undergoing coronary artery bypass grafting surgery (CABGS).
      There is an association between older age and need for prolonged mechanical
      ventilation (MV); however, it is unclear what other presurgical characteristics
      may contribute to prolonged time on the ventilator in older adults. OBJECTIVE: To
      develop and validate a probability model for prolonged MV utilizing selected
      presurgical patient characteristics. METHOD: A retrospective, nonexperimental
      design was utilized to study 548 Medicare recipients (65 years of age or older)
      undergoing CABGS during 1998. Data were obtained from an existing coronary artery
      surgery clinical database. RESULTS Based on extubation time, the sample was
      comprised of two groups (Group 1, N = 205; MV <or= 5 hours. Group 2, N = 343; MV
      > 5 hours). Using logistic regression modeling, predictors of late extubation
      included: (a). age of 80 years or older (odds ratio [OR] 2.99, p =.003), (b).
      female sex (OR = 1.76, p =.011), (c). hypertension (OR = 1.60, p =.018), (d).
      urgent or emergent preoperative clinical status (OR = 3.04, p =.002), and (e).
      prior CABGS (OR = 2.14, p =.009). The predictive model provided moderate
      discrimination of time to extubation group (concordance statistic = 0.656).
      CONCLUSIONS: Older age, urgent or emergent preoperative clinical status, and
      prior CABGS are risk factors for prolonged MV, which have been consistently
      identified in combined adult and older adult samples. Female sex and hypertension
      have not been well supported in earlier studies as risk factors for prolonged MV.
      The exploratory model provides a preliminary indication of factors placing
      Medicare recipients at risk for late extubation, but requires further development
      and testing for use by nurses in clinical practice.

PMID- 14726777
TI  - Effects of booster interventions on factory workers' use of hearing protection.
AB  - BACKGROUND: The provision of reinforcements or boosters to interventions is seen
      as a logical approach to enhancing or maintaining desired behavior. Empirical
      studies, however, have not confirmed the effectiveness of boosters nor assessed
      the optimum number of boosters or the timing for their delivery. OBJECTIVES: This
      randomized controlled trial contrasted the effect of four booster conditions (a).
      30 days; (b). 90 days; (c). 30 and at 90 days; and (d). no boosters of the
      intervention to increase the use of hearing protection devices (HPDs). METHODS: A
      total of 1325 factory workers completed a computerized questionnaire and were
      randomly assigned to one of three computer-based (tailored, nontailored predictor
      based, or control) multimedia interventions designed to increase the use of
      hearing protection devices. After the intervention, colorful boosters specific to
      the type of training received were mailed to workers' homes. Posttest measures of
      use were administered at the time of their next annual audiogram 6 to 18 months
      after the intervention. RESULTS Repeated measures of analysis of variance (ANOVA)
      showed a significant main effect for the booster (after 30 days) in the group
      that received tailored training (F[3442] = 2.722; p =.04). However, in the
      assessment of the interaction between time (pretest and posttest) and boosters
      (four groups), the ANOVA did not find significant differences in hearing
      protection device use for any of the training groups. To assess for significant
      differences between groups, post hoc comparisons were conducted at the pretest
      and posttest for the total sample and for the subsample of workers who reported
      using hearing protection devices less than 100% of the time needed. Sheffe
      contrasts by intervention group, gender, ethnicity, and hearing ability found no
      significant changes in the mean use of hearing protection devices for the booster
      groups. CONCLUSIONS: Although the provision of boosters represented a
      considerable commitment of resources, their use was not effective in this study.
      However, it would be premature to eliminate boosters of interventions. Further
      study is needed to explore the effects of different booster types for increasing
      the use of hearing protection devices, and to assess carefully the effects of
      boosters on other health behaviors in studies with controlled designs.

PMID- 14726778
TI  - SPSS and SAS programming for the testing of mediation models.
AB  - BACKGROUND: Mediation modeling can explain the nature of the relation among three
      or more variables. In addition, it can be used to show how a variable mediates
      the relation between levels of intervention and outcome. The Sobel test,
      developed in 1990, provides a statistical method for determining the influence of
      a mediator on an intervention or outcome. Although interactive Web-based and
      stand-alone methods exist for computing the Sobel test, SPSS and SAS programs
      that automatically run the required regression analyses and computations increase
      the accessibility of mediation modeling to nursing researchers. OBJECTIVES: To
      illustrate the utility of the Sobel test and to make this programming available
      to the Nursing Research audience in both SAS and SPSS. METHODS: The history,
      logic, and technical aspects of mediation testing are introduced. The syntax
      files sobel.sps and sobel.sas, created to automate the computation of the
      regression analysis and test statistic, are available from the corresponding
      author. RESULTS: The reported programming allows the user to complete mediation
      testing with the user's own data in a single-step fashion. A technical manual
      included with the programming provides instruction on program use and
      interpretation of the output. CONCLUSION: Mediation modeling is a useful tool for
      describing the relation between three or more variables. Programming and manuals
      for using this model are made available.

PMID- 14726779
TI  - Intervention fidelity.
AB  - BACKGROUND: Although an assumption of consistency in intervention delivery is key
      to the conclusion that the findings are valid, attention to both interventionist
      adherence and competence has not become a standard in nursing intervention
      research. OBJECTIVES: The purpose of this article is to describe the technology
      model of intervention fidelity as it applies to psychosocial interventions, and
      to propose its application in nursing intervention research as a way to support
      accurate conclusions about validity. METHODS: The features and methods of the
      Technology Model of intervention fidelity were reviewed. The review included
      development of a manual, training and supervision of interventionists,
      measurement of intervention fidelity, and inclusion of intervention fidelity as
      an independent variable in the analysis. RESULTS: The Technology Model and the
      associated methodologies that have been used to monitor psychosocial intervention
      fidelity in psychiatry can be adapted and applied by nursing. Monitoring costs
      can be managed through use of a general system that can be applied across
      programmatic or related studies. CONCLUSIONS: Application of the Technology Model
      of intervention fidelity could advance the maturation of nursing intervention
      research and evidence-based clinical practice.

PMID- 14726780
TI  - To transform or not transform skewed data for psychometric analysis: that is the
      question!
AB  - BACKGROUND: Although data transformation is generally recommended, its benefits
      of have not been widely studied. This report reviews evidence regarding the costs
      and benefits of transforming skewed data with respect to two statistics commonly
      used in psychometric analyses: the Cronbach alpha and the Pearson product-moment
      correlation. METHODS: Data describing 758 immigrants from the former Soviet Union
      who completed a Russian language version of the Symptom Checklist-90-Revised (SCL
      90-R) were used to demonstrate the effects of transformation. More than half
      (55%) of the SCL-90-R items had a problematic skew. The Cronbach alpha and the
      Pearson product-moment correlation were calculated for original item responses as
      well as for square root and log transformations of these responses. Sample size
      (full, 30%, 20%), transformation type (square root or log transformation), and
      transformation method (sum items first and then transform, transform items first
      and then sum) were manipulated to evaluate the relevance of these factors to
      transformation. RESULTS: Regardless of sample size, neither the Cronbach alpha
      nor the Pearson product-moment correlation showed a difference between original
      and transformed data, with one exception. When items were transformed first
      before being summed in the calculation of the Pearson product-moment correlation,
      inconsistently higher (+.05) or slightly lower values (-.01) were observed
      relative to those created with the nontransformed data across the different
      sample sizes. CONCLUSIONS: These findings suggest that data transformation is not
      always needed or advisable when the Cronbach alpha or Pearson product-moment
      correlation is calculated for instruments with skewed item responses.

PMID- 14726781
TI  - Is single-payer national health insurance the answer?

PMID- 14726782
TI  - Practice and politics.

PMID- 14726783
TI  - Yes to your November editorial!

PMID- 14726784
TI  - Abnormal pap anxiety.

PMID- 14726785
TI  - Celiac sprue article appreciated.

PMID- 14726786
TI  - Type 2 diabetes: treat to target.
AB  - Traditionally, practitioners have reserved insulin therapy for patients with type
      2 diabetes until diet, exercise, and treatment with oral agents have failed to
      maintain glycemic control. Increasing evidence, however, supports advancing
      insulin therapy earlier in treating diabetes, not only to normalize glycemic
      control and emulate normal physiologic insulin secretion, but also to delay or
      prevent disease-associated comorbidity.

PMID- 14726787
TI  - Sixteenth annual legislative update: how each state stands on legislative issues
      affecting advanced nursing practice.

PMID- 14726789
TI  - Collecting data from practitioners: advice to researchers.

PMID- 14726790
TI  - Dear Florence: tips and strategies for faculty.

PMID- 14726791
TI  - Planning for a new baby: a creative approach to learning.

PMID- 14726792
TI  - Teaching strategies used with success in the multicultural classroom.

PMID- 14726793
TI  - Technology in nursing education: five axioms.

PMID- 14726794
TI  - Strategies to promote success on the NCLEX-RN for students with English as a
      second language.
AB  - Faced with an increasingly diverse population and a shortage of nurses, US
      schools of nursing need to educate nurses from diverse backgrounds. These
      students may use English as a second language (ESL), leading to challenges that
      can place them at risk for not passing the NCLEX-RN. The authors present several
      challenges for ESL students preparing for the NCLEX-RN and successful strategies
      to coach them. These preparation issues and strategies may also help foreign
      educated nurses prepare for the NCLEX-RN.

PMID- 14726795
TI  - Reflective journaling: developing an online journal for distance education.
AB  - Reflective journal writing can be a useful heuristic tool to foster critical
      thinking skills and develop reflective clinical practice in nursing. When
      combined with a distance education delivery format, the online journal helps to
      leverage the strengths of reflective learning with educational technology as well
      as provide a seamless record of learning outcomes across the curriculum. The
      authors discuss the incorporation of an online reflective journal into a distance
      education clinical course and provide guidelines for educators considering a
      similar approach.

PMID- 14726796
TI  - Enhancing clinical practice and education with high-fidelity human patient
      simulators.
AB  - Research shows that students exhibit increased autonomy and self-confidence when
      delivering patient care after practicing first with high-fidelity human patient
      simulators (HPS). Practicing clinical skills on a high-fidelity HPS allows
      students to learn in a highly adaptable, safe educational environment that
      fosters autonomy, independence, and the development of sound analytical skills.
      The author discusses the use of patient simulators in nursing education, a
      definition of a high-fidelity HPS, and their value to clinical practice and
      education. A cost-effective example of how to acquire a high-fidelity HPS without
      going over budget is provided.

PMID- 14726797
TI  - Community partnerships for an LPN to BSN career mobility project.
AB  - Based on a 6-year, learn and earn curriculum, the authors report on a year-old
      project that assists licensed practical nurses (LPNs) to obtain a baccalaureate
      degree in nursing (BSN). Partnerships with 4 area healthcare agencies employing
      LPNs were developed to support students with full or partial tuition
      reimbursement and work schedules to accommodate classes. Key university staff in
      the offices of admissions, financial aid, adult programs and services, and
      nursing advisement are assigned to this student group to provide individualized
      assistance. The authors discuss unique components of the project including
      regularly scheduled role transition seminars, faculty mentors, BSN and nurse
      practitioner clinical mentors, and clinical experiences in nurse-managed clinics.

PMID- 14726798
TI  - Media as a teaching tool in psychiatric nursing education.
AB  - The authors describe a course in psychiatric nursing where media in the form of
      literature, film, and music were used as teaching strategies. The purpose was to
      enhance students' sensitivity to the personal experiences of psychiatric patients
      while also broadening students' understanding of mental illness and the
      institutions developed to treat it. Students' critical reading, thinking, and
      analytic skills were cultivated, along with introspection and self-reflection.

PMID- 14726799
TI  - Management curriculum redesign: integrating customer expectations for new
      leaders.
AB  - Tumultuous and dynamic changes in the healthcare environment have resulted in
      unprecedented stresses and challenges for both nursing education and nursing
      practice. It is essential that nursing education curricula reflect the rapidly
      changing technologies and dramatically expanding knowledge and changes in the
      practice environment and incorporate theory, science, professional standards, and
      consumer/service input. The authors describe a redesigned undergraduate
      management curriculum.

PMID- 14726800
TI  - The clinical impact of multiresistant gram-positive microorganisms in long-term
      care facilities.

PMID- 14726801
TI  - A case report of hyponatremia with citalopram use.

PMID- 14726802
TI  - Incidence of venous thromboembolism in megestrol acetate users.

PMID- 14726803
TI  - Donepezil in advanced dementia, or delirium?

PMID- 14726804
TI  - Attention deficit/hyperactivity disorder (ADHD): complex phenotype, simple
      genotype?
AB  - Complex genetic traits refer to those phenotypes not fitting patterns of
      Mendelian segregation and/or assortment but exhibiting a preferential familial
      clustering that cannot be explained by cultural or environmental causes.
      Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurodevelopmental disorder of childhood and probably the most controversial.
      ADHD has been considered a complex genetic trait based upon the absence of a
      clear-cut boundary between affected and unaffected status. Furthermore, its high
      comorbidity with other disorders strongly suggests complex epistatic or
      pleiotropic effects acting in common with the environmental influences. This
      implies that the same gene or genes is or are associated with different and
      concurrently occurring phenotypes. In this study, we will review clinical and
      epidemiological aspects related to the ADHD phenotype, which are considered
      either as categorical or continuous traits. We also will discuss genetic models
      underlying the complexity of this behavioral phenotype and the probable role of
      epistatic interactions between major genes contributing to the ADHD phenotype.

PMID- 14726805
TI  - Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3,
      RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review.
AB  - Severe combined immunodeficiency (SCID) is an inherited immune disorder
      characterized by T-cell lymphopenia (TCLP), a profound lack of cellular (T-cell)
      and humoral (B-cell) immunity and, in some cases, decreased NK-cell number and
      function. Affected children develop severe bacterial and viral infections within
      the first 6 months of life and die before 1 year of age without treatment.
      Mutations in any of eight known genes: IL2RG, ARTEMIS, RAG1, RAG2, ADA, CD45,
      JAK3, and IL7R cause SCID. Mutations in unidentified genes may also cause SCID.
      Population-based genotype and allelic frequencies of these gene defects have not
      been measured. Some minimal estimates of SCID prevalence are presented.
      Currently, hematopoietic stem cell transplants are the standard treatment. In
      clinical trials, gene therapy has been used to reconstitute immune function in
      patients with IL2RG and ADA defects. The availability of effective therapies,
      plus the short asymptomatic period after birth, (when stem-cell transplantation
      is most effective), make SCID a potentially good candidate for newborn screening.
      Dried blood spots are currently collected from all infants at birth for newborn
      metabolic screening. Tests for TCLP on dried blood spots could be developed as a
      screen for SCID. Because SCID may be unrecognized, with infant deaths from
      infection attributed to other causes, newborn screening is the only way to
      ascertain true birth prevalence. Validated tests and pilot population studies are
      necessary to determine newborn screening's potential for identifying infants with
      SCID.

PMID- 14726806
TI  - Biopterin responsive phenylalanine hydroxylase deficiency.
AB  - PURPOSE: Phenylketonuria (PKU) is an autosomal recessive disorder caused by
      mutations in the phenylalanine hydroxylase (PAH) gene. There have been more than
      400 mutations identified in the PAH gene leading to variable degrees of
      deficiency in PAH activity, and consequently a wide spectrum of clinical
      severity. A pilot study was undertaken to examine the response to 6-R-l-erythro
      5,6,7,8-tetrahydrobiopterin (BH4) in patients with atypical and classical PKU.
      METHODS: PAH gene mutation analysis was performed using denaturing gradient gel
      electrophoresis and gene sequencing. Patients with classical, atypical, or mild
      PKU were orally given BH4 10 mg/kg. Blood phenylalanine and tyrosine levels were
      determined using tandem MS/MS at 0 hours, 4 hours, 8 hours, and 24 hours
      intervals. RESULTS: Thirty-six patients were given a single oral dose of 10 mg/kg
      of BH4. Twenty one patients (58.33%) responded with a decrease in blood
      phenylalanine level. Of the patients that responded, 12 were classical, 7
      atypical, and 2 mild. The mean decline in blood phenylalanine at 24 hours was >
      30% of baseline. There were 15 patients who did not respond to the BH4 challenge,
      14 of those had classical and one had atypical PKU. Mapping the mutations that
      responded to BH4 on the PAH enzyme showed that mutations were in the catalytic,
      regulatory, oligomerization, and BH4 binding domains. Five patients responding to
      BH4 had mutations not previously identified. CONCLUSION: The data presented
      suggest higher than anticipated number of PKU mutations respond to BH4, and such
      mutations are on all the domains of PAH.

PMID- 14726807
TI  - Genetic determinants of osteoporosis susceptibility in a female Ashkenazi Jewish
      population.
AB  - PURPOSE: To determine the heritability of low bone mineral density (BMD) at the
      hip in Ashkenazi Jewish families. METHODS: BMD at hip was accessed by dual x-ray
      absorptiometry (DEXA) in 166 female subjects from 61 families. Variance component
      analysis was used to estimate genetic contributions. RESULTS: We observed
      significant genetic contributions to age-adjusted BMD at the femoral neck as
      measured by heritability 0.67 (P < 0.0001). CONCLUSION: There is significant
      genetic determination in decreased BMD at the femoral neck in an Ashkenazi Jewish
      female population. These results warrant further gene mapping studies in this
      population to identify osteoporosis susceptibility loci.

PMID- 14726808
TI  - An epidemiologic assessment of genomic profiling for measuring susceptibility to
      common diseases and targeting interventions.
AB  - PURPOSE: The current clinical value of genomic profiling (testing for genotypes
      at multiple loci) for assessing susceptibility to common diseases and targeting
      behavioral and medical interventions is questionable. As common diseases result
      from many gene-environment interactions, epidemiologic studies should be used to
      examine the value of genomic profiling in terms of clinical validity (future
      disease positive and negative predictive value stratified by exposure), clinical
      utility (targeted interventions to reduce disease risk among persons with the
      profile) and public health utility (comparing reduction of disease burden in the
      population based on genomic profiling to population-wide interventions). METHODS:
      We investigate these parameters for a hypothetical common disease (5% lifetime
      risk), for which 3 genetic variants at different loci and one environmental
      exposure are risk factors. RESULTS: We show that even for modest effects of each
      variant alone (risk ratios from 1.5-3.0) and modest interactions between the
      exposure and the genes, the disease predictive value for people with 2 or more
      variants (especially 3) can be quite high (50-100%) in the presence of a
      modifiable exposure. Individual risks can then be reduced by targeted exposure
      intervention among persons with the genotype. However, the predictive value for
      multiple genotypes is much lower for rarer diseases (< 1 per 1000). Also, with
      increasing number of genes in a profile, the population impact of disease
      reduction for targeted intervention based on genotype will be smaller, especially
      for rare genotypes, weak associations, and weak interactions. CONCLUSION: To
      assess the value of genomic profiling, well-designed epidemiologic studies are
      needed to quantify disease risks, in addition to costs, benefits, and risks for
      testing and interventions.

PMID- 14726809
TI  - A set of commercially available fluorescent in-situ hybridization probes
      efficiently detects cytogenetic abnormalities in patients with chronic
      lymphocytic leukemia.
AB  - PURPOSE: To investigate a simplified panel of fluorescent in-situ hybridization
      (FISH) probes for evaluation of patients with chronic lymphocytic leukemia (CLL)
      and to correlate results from this technique with known prognostic factors.
      METHODS: We retrospectively reviewed the FISH and conventional cytogenetic
      results, and clinical and laboratory data of 44 patients with CLL. RESULTS: FISH
      was more sensitive than conventional cytogenetics in detecting genomic
      aberrations (75% vs. 16%, P < 0.0001). Trisomy 12 was significantly correlated
      with the cell surface marker of CD38 expression (P = 0.0017). CONCLUSION: This
      FISH panel reliably detects prognostically important genomic abnormalities in CLL
      and is suitable for widespread use.

PMID- 14726810
TI  - Single umbilical artery: what does it mean for the fetus? A case-control analysis
      of pathologically ascertained cases.
AB  - PURPOSE: To ascertain the frequency of chromosomal and other anomalies in fetuses
      with single umbilical artery. METHODS: Placentas with single umbilical artery
      were identified from hospital pathology laboratory records. For each identified
      case, the next consecutive placenta with two umbilical arteries served as a
      control. Pathology records, maternal histories, and prenatal ultrasounds when
      available were reviewed for congenital anomalies, pregnancy complications, and
      maternal characteristics. When indicated, placental specimens, amniocytes, or
      neonatal bloods were karyotyped. RESULTS: Single umbilical artery existed in 2.0%
      (97/4846) of pathological specimens. Fetuses with single umbilical artery had
      significantly more chromosomal (10.3% vs. 1.0%) and other congenital anomalies
      (27% vs. 8%). CONCLUSIONS: The high incidence of major chromosomal and congenital
      anomalies justifies detailed fetal ultrasonography, echocardiography, and
      amniocentesis for karyotype when single umbilical artery is discovered during
      routine ultrasound.

PMID- 14726811
TI  - Direct-to-consumer genetic testing: access and marketing.

PMID- 14726812
TI  - ACMG statement on direct-to-consumer genetic testing.

PMID- 14726813
TI  - Technical standards and guidelines for Huntington disease testing.
AB  - One mission of the ACMG Laboratory Quality Assurance (QA) Committee is to develop
      standards and guidelines for clinical genetics laboratories, including
      cytogenetics, biochemical, and molecular genetics specialties. This document was
      developed under the auspices of the Molecular Subcommittee of the Laboratory QA
      Committee by the Huntington Disease (HD) Working Group. These guidelines are not
      to be interpreted as restrictive or the only approach but to provide a helpful
      guide. Certainly, appropriately trained and credentialed laboratory directors
      have flexibility to utilize various testing platforms and design testing
      strategies with considerable latitude. We felt that it was essential to include
      technique-specific guidelines of several current technologies commonly used in
      laboratories providing HD testing, because the technologies discussed are
      available commercially and are widely utilized. We take the view that these
      technologies may change, and thus this document may change with future review.

PMID- 14726814
TI  - Revised sections F7.5 (quantitative amino acid analysis) and F7.6 (qualitative
      amino acid analysis): American College of Medical Genetics Standards and
      Guidelines for Clinical Genetics Laboratories, 2003.
AB  - Determination of plasma amino acid levels has become a key piece of information
      in the diagnosis and clinical management of a group of metabolic genetic
      disorders. Appropriate laboratory methodologies have been published for amino
      acid analysis, yet there is a need for direction for the laboratory in performing
      this testing. The following guidelines were generated by a working group of the
      American College of Medical Genetics Laboratory Quality Assurance Committee.
      Based upon a body of knowledge and professional experience, these guidelines and
      standards are to be the benchmark for performance of amino acid analysis for
      clinical interpretation.

PMID- 14726815
TI  - No evidence for heterozygote advantage at MTHFR in patients with lumbosacral
      myelomeningocele or their relatives.

PMID- 14726816
TI  - Spitzoid tumors: a matter of perspective?

PMID- 14726817
TI  - Differential diagnosis of cutaneous infiltrates of B lymphocytes with follicular
      growth pattern.
AB  - The differential diagnosis of cutaneous B-cell infiltrates with follicular
      pattern of growth is one of the most vexing problems in dermatopathology. In this
      study we focused on histopathologic, immunophenotypic, and molecular differential
      diagnostic criteria between Borrelia burgdorferi (Bb)-associated lymphocytoma
      cutis (LC), primary cutaneous follicle center cell lymphoma (FCCL), and primary
      cutaneous marginal zone lymphoma (MZL) with reactive germinal centers (GCs). A
      total of 47 patients were included in the study, including 12 cases of LC (M:F =
      2:1; mean age: 38.0; median: 31; range: 9-75), 29 cases of FCCL (M:F = 1.2:1;
      mean age: 57.5; median: 57; range: 24-97), and 6 cases of MZL (M:F = 1:1; mean
      age: 63.8; median: 67.5; range: 38-86). In all cases complete phenotypic data
      were available. In addition, the IgH gene rearrangement and the t(14;18) were
      analyzed using the polymerase chain reaction technique (PCR) in 41 (FCCL = 27, LC
      = 10, MZL = 4) and 18 cases (FCCL = 15, LC = 2, MZL = 1), respectively. Histology
      revealed in all cases of FCCL one or more atypical feature of the follicles
      including the lack of or a reduced mantle zone, lack of polarization, tendency to
      confluence, and absence of tingible body macrophages. In most cases of Bb
      associated LC, the GCs were devoid of mantle zone, lacked polarization, and
      revealed tendency to confluence as well, but all cases showed the presence of
      several tingible body macrophages. In MZL, follicles showed typical features of
      reactive GCs. Immunohistology revealed a reduced proliferative activity of
      neoplastic follicles as detected by MIB-1 antibody in 23 of 29 cases of FCCL
      (79.3%), but only in 1 case of LC (8.3%). Proliferation of the GCs was normal in
      all cases of MZL. Positivity for CD10 and/or Bcl-6 was found in small clusters
      outside the follicles in 19 cases of FCCL (65.5%), and in 3 cases of LC (25%),
      but in no case of MZL. The intensity of CD10 staining on follicular cells on
      average was stronger in cases of FCCL, but overlapping features could be
      observed. Finally, staining for Bcl-2 protein was consistently negative on GC
      cells in cases of LC and MZL, and was positive on a variable proportion of the
      cells in 8 cases of FCCL (28.6%). Molecular analyses showed no evidence of the
      t(14;18) in all cases tested. Analysis of the IgH gene rearrangement revealed a
      monoclonal pattern in 1 of 10 cases of LC (10%), 14 of 27 cases of FCCL (51.9%),
      and 2 of 4 cases of MZL (50%) tested. In summary, Bb-associated LC and FCCL show
      sometimes overlapping histopathologic, immunohistochemical, and molecular
      features, whereas follicles in MZL show clear-cut aspects of reactive GCs.
      Absence of tingible body macrophages within follicles, reduced proliferation of
      the follicles as detected by immunohistology, presence of positivity for Bcl-2
      protein within follicular cells, and monoclonality by PCR are the main criteria
      suggestive of malignancy. Diagnosis of cutaneous infiltrates of B lymphocytes
      with follicular growth pattern should be achieved by integration of clinical data
      with histopathologic, immunohistochemical, and molecular features of the lesions.

PMID- 14726818
TI  - Cutaneous epithelioid angiomatous nodule: a distinct lesion in the morphologic
      spectrum of epithelioid vascular tumors.
AB  - Cutaneous epithelioid vascular proliferations comprise a morphologic spectrum
      ranging from benign, reactive to frankly malignant conditions. We present a group
      of morphologically distinct epithelioid vascular lesions in the skin that defy
      classification according to current criteria. Clinically, the lesions presented
      as single (14/15) or multiple (1/15) small (< 1.5 cm, median = 0.5 cm)
      erythematous to bluish nodules or papules of short duration (weeks to months)
      without gender predilection (M:F = 1:1). Age distribution ranged from 15 to 79
      years (median: 37). Lesions were predominantly located on the trunk (8/15) but
      also involved the extremities (5/15), face (1/15), and nasal mucosa (1/15). No
      patient was immunocompromised. Treatment was simple surgical excision.
      Histologically, the lesions were located superficially in dermis (or submucosa)
      and consisted of a circumscribed, unilobular, mainly solid proliferation of large
      polygonal epithelioid endothelial cells with vesicular nuclei and conspicuous
      nucleoli. Cytoplasm was abundant and contained frequent intracytoplasmic
      vacuoles. Nuclear atypia was absent. Mitotic figures (up to 5/10HPF) were
      observed in 8 lesions. Formation of endothelial-lined channels was a focal but
      constant feature. Also noted were adjacent dilated dermal vessels (8/15),
      hemosiderin deposition (6/15), and mild fibrosis (9/15). The lesion was
      accompanied by a chronic inflammatory infiltrate with a lymphoplasmacytic
      component (14/15), most pronounced at the periphery of the lesion, and varying
      numbers of eosinophils scattered throughout the lesion (12/15). Eosinophils were
      conspicuous in only 4 cases. Epidermal hyperplasia was present in 11 cases. By
      immunohistochemistry, lesional cells stained positively for at least one
      endothelial marker. Clinical follow-up (median = 30 months) showed no recurrence
      or metastases. Epithelioid angiomatous nodule is a benign, likely reactive
      cutaneous lesion in the clinical and morphologic spectrum of epithelioid vascular
      proliferations. It differs from conventional epithelioid hemangioma both in its
      clinical presentation with predominant involvement of trunk and extremities as
      well as its histologic features, which more closely resemble epithelioid
      angiosarcoma.

PMID- 14726819
TI  - P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell
      carcinoma.
AB  - The histologic boundary between actinic keratosis, Bowen disease, and invasive
      squamous cell carcinoma is not clear in many cases. We determined nuclear
      expression of p27 (a protein associated with cellular quiescence) and Ki-67 (a
      marker of proliferation) immunohistochemically in actinic keratosis, Bowen
      disease, and squamous cell carcinoma to see if differential patterns of
      expression for p27 exist and how these might correlate with Ki-67 expression. We
      determined a labeling index for p27-stained nuclei and assessed the pattern of Ki
      67 expression. The student's t test was used to evaluate the p27 labeling index.
      The p27 labeling index was decreased in invasive aggregates of squamous cell
      carcinoma (76.9+/- 1.1%) when compared with those of normal epidermis (97.2+/-
      2.4%), actinic keratosis (95.3 +/- 1.4%), and Bowen disease (98.0+/- 0.5%). Ki-67
      was expressed in a scattered to confluent linear pattern in the basal/parabasal
      cell layer of normal epidermis and actinic keratosis. Keratinocytes in squamous
      cell carcinoma exhibited Ki-67 in the peripheral layers of the neoplasm and
      frequently within the tumor aggregates. Ki-67 was observed in nuclei throughout
      the full thickness of the epidermis in Bowen disease. The staining pattern of Ki
      67 in Bowen disease separated this entity from others under study. The
      combination pattern of p27 and Ki-67 staining can be used to support
      differentiation of actinic keratosis, Bowen disease, and squamous cell carcinoma.

PMID- 14726820
TI  - Absence of intercellular adhesion molecule 1 expression in varicella zoster virus
      infected keratinocytes during herpes zoster: another immune evasion strategy?
AB  - Downregulation of major histocompatibility complex (MHC) class I, MHC-II, and
      intercellular adhesion molecule 1 (ICAM-1) expression in infected cell lines
      allows some viruses to escape host immunity. In skin lesions of varicella zoster
      virus (VZV), MHC-II transcripts were demonstrated in keratinocytes around
      vesicles, but not in VZV-infected cells. Whether other immunoevasive mechanisms
      are present during herpes zoster (HZ) is not yet elucidated. The aim of the study
      was to disclose the temporal immunohistochemical expression of immune escape
      mechanisms during HZ. Sequential skin biopsies were performed in 5 HZ patients.
      VZV IE63, CD1a, CD3, CD4, CD8, CD56, CD68, L1, HLA-DR, HLA-ABC, interleukin (IL)
      6, IL-10, interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha),
      and ICAM-1 expressions were assessed on frozen sections using
      immunohistochemistry. Controls consisted of normal skin, herpes simplex virus
      (HSV) skin infections, and other distinct bullous skin diseases. HLA-DR and ICAM
      1 expressions were not observed in VZV- and HSV-infected keratinocytes,
      contrasting with their upregulation in the surrounding epidermis and inside
      nonviral blisters. However, HLA-ABC expressions were not inhibited in VZV
      infected keratinocytes. Furthermore, the CD4/CD8 ratio remained unmodified during
      the infection evolution, and this ratio was variable among patients. Increased
      IFNgamma, TNFalpha, and IL-6 expressions were present, but IL-10 expression only
      increased in later stages. In contrast to in vitro MHC-I and MHC-II
      downregulation, VZV infection is related to MHC-II but not MHC-I expression on
      infected keratinocytes. The absence of ICAM-1 expression on infected
      keratinocytes may reduce their antigen presentation capacities to LFA-1 ligand
      bearing T cells. This may represent another VZV-associated immune escape
      mechanism. Increased IFNgamma, TNFalpha, and IL-6 expressions suggest a TH1
      profile.

PMID- 14726821
TI  - Alopecia mucinosa is mycosis fungoides.
AB  - Confusion abounds regarding the terms "follicular mucinosis" and "alopecia
      mucinosa," not only concerning definition and essential character, but of
      relationships between themselves on one hand and between themselves and mycosis
      fungoides on the other. We address here those issues in methodical fashion, first
      in historical perspective by review, scrupulously and critically, of what has
      been said in the many articles devoted to the subject; we next tell how the terms
      "alopecia mucinosa" and "follicular mucinosis" came to be and how they are
      employed currently; we then set forth our own observations pertinent to clinical,
      histopathologic, and biologic aspects of the condition called, conventionally,
      "alopecia mucinosa," those observations based on our own findings in sections of
      tissue cut from 54 biopsy specimens taken from 45 patients, all of them having
      been signed out previously as "follicular mucinosis;" we proceed to forge clinico
      pathologic correlation of lesions in 14 of those 45 patients, utilizing
      assessments, by examination grossly and microscopically, of attributes in the
      very same lesion. Last, we propose a concept, and a terminology that derives from
      it, that synthesizes all that is known now about "alopecia mucinosa" and
      "follicular mucinosis," in particular the relationship of "alopecia mucinosa" to
      mycosis fungoides, including "follicular," "syringotropic," and erythrodermic
      manifestations of it. In short, we affirm that so-called alopecia mucinosa is but
      one of many morphologic manifestations of mycosis fungoides.

PMID- 14726822
TI  - Ichthyosis and keratotic follicular plugs containing dystrophic calcification in
      newborns: distinctive histopathologic features of x-linked dominant
      chondrodysplasia punctata (Conradi-Hunermann-Happle syndrome).
AB  - Prior to the recent characterization of the enzymatic defect and identification
      of the involved gene, the histopathology of X-linked dominant chondrodysplasia
      punctata (Conradi-Hunermann-Happle syndrome or CDPX2) has been described under
      various names including calcinosis universalis, chondrodystrophia calcificans
      congenita, Conradi disease, and Conradi-Hunermann syndrome. We present two
      newborns with characteristic ichthyosiform erythroderma noted at birth.
      Radiographs demonstrated chondrodysplasia punctata in one patient. Although the x
      ray performed at birth was negative in the other patient, sterol analyses of the
      keratotic scales were diagnostic for CDPX2. Skin biopsies from both patients
      showed thick laminated orthokeratosis and prominent keratotic follicular plugs
      containing dystrophic calcification. We also retrospectively examined 20 cases of
      various types of ichthyosis seen over a 23-year period at our institution.
      Intracorneal calcium deposition was not seen in any of these cases. As
      demonstrated by our cases and review of the literature, dystrophic calcification
      in the keratotic plug is a distinctive histopathologic feature of Conradi
      Hunermann-Happle syndrome in newborns and is not seen in other known forms of
      ichthyoses.

PMID- 14726823
TI  - Sarcoidal-type allergic contact granuloma: a rare complication of ear piercing.
AB  - As body piercing is increasingly en vogue, complications are on the rise as well.
      Biopsies of such lesions can impose special problems to the reviewing
      dermatopathologist. We present two patients who developed papulonodular lesions
      at the sites of ear piercings. Unexpectedly, the findings included prominent
      sarcoidal granuloma formation with confluent areas of fibrinoid necrosis. An
      infectious etiology was excluded. However, patch testing revealed contact allergy
      to palladium, platinum, and nickel. Interestingly, histopathologic examination of
      the patch test sites also demonstrated granuloma formation. These findings
      suggest that the lesions represent allergic contact granulomas. When confronted
      with this special type of tissue reaction in skin biopsies of piercing sites, the
      reviewing dermatopathologist should consider the possibility of an allergic
      reaction. Careful history and thorough diagnostic procedures, including biopsy of
      the patch test site can establish the diagnosis of contact allergic granuloma.

PMID- 14726824
TI  - Epstein-Barr virus-induced transformation of cutaneous plasmacytoma into CD30+
      diffuse large B-cell lymphoma.
AB  - A unique, previously unreported case of transformation of cutaneous plasmacytoma
      into CD30+ large B-cell lymphoma is described. Both neoplastic components were
      immunophenotypically distinct. The plasma cells were CD20-, CD30-, CD43+, CD45+,
      lambda +; the blasts were CD20+, CD30+, CD43-, and CD45-. The large B-cell
      lymphoma has gradually become a predominant component of the neoplastic nodules.
      While plasma cells and blasts were both positive for Epstein-Barr virus-encoded
      nuclear RNAs (EBER-1), the EBV-latent membrane antigen 1 (EBV-LMP1) was expressed
      only in the minority of the blasts and not in the plasma cells. The neoplastic
      process has remained confined to the skin for more than six years since its
      development.

PMID- 14726825
TI  - Cystic basal cell carcinoma or hidrocytoma? The use of an excisional biopsy in a
      histopathologically challenging case.
AB  - Basal cell carcinoma (BCC) has many histologic variants. These variants may show
      differentiation toward benign and malignant tumors of cutaneous appendages,
      especially hair follicles. Herein we describe a lesion that was clinically
      thought to be a BCC, but a superficial biopsy showed histologic features
      suggestive of an apocrine hidrocystoma. Because of some cytologic atypia,
      complete excision was recommended. The excision specimen revealed a cystic BCC.
      The importance of examining the entire neoplasm before reaching a final
      pathologic diagnosis is emphasized.

PMID- 14726826
TI  - Dermatophyte-related granular parakeratosis.
AB  - A patient presented with a two-month history of an annular eruption on her back.
      Biopsies of this process revealed dermatophytosis and concurrent granular
      parakeratosis. This patient's eruption resolved completely with antifungal
      therapy suggesting that the fungal organisms caused the granular parakeratosis.

PMID- 14726827
TI  - Intraneural dendritic cell neurofibroma with pseudorosettes.
AB  - Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a recently proposed
      variant of neurofibroma. However, its peripheral nerve sheath origin has
      subsequently been questioned, and it has been suggested that the neoplasm could
      represent a hitherto undescribed variant of melanocytic nevus with neural
      differentiation. Here we report a case of DCNWPR that arose almost exclusively
      within the confinement of the perineurium in the skin. This observation gives
      further evidence that this entity is a peripheral nerve sheath tumor and is
      unrelated to melanocytic neoplasms.

PMID- 14726828
TI  - The sign-out method you employ matters: one diagnosis is not always enough as
      illustrative.

PMID- 14726829
TI  - Homonymous epidermotropism.

PMID- 14726830
TI  - Immunohistochemistry in epidermolysis bullosa diagnosis.

PMID- 14726831
TI  - Pigmented atypical fibroxanthoma, a dermatofibroma variant?

PMID- 14726833
TI  - [Entrapment of the long head of the biceps: the "hourglass biceps". Another cause
      of pain and locking of the shoulder].
AB  - PURPOSE OF THE STUDY: We describe a mechanical condition affecting the long head
      of the biceps tendon (LHBT) causing potentially unrecognized entrapment within
      the joint and subsequent pain and locking. This is caused by a hypertrophic intra
      articular portion of the tendon that is unable to slide into the bicipital groove
      during elevation of the arm. MATERIALS AND METHODS: Twenty one patients were
      identified, during open (14 cases) or arthroscopic (7 cases) surgery, with a so
      called "hourglass biceps" i.e., hypertrophic intraarticular portion of the LHBT
      and incarceration of the tendon during elevation. All cases occurred in
      conjunction with a rotator cuff rupture except one who had a partial deep tear.
      All patients were treated by excision of the biceps, after tenodesis or bipolar
      tenotomy, and appropriate treatment of the concomitant lesions. RESULTS: All
      patients presented with anterior shoulder pain and loss of passive elevation
      averaging 10-20 degrees. A dynamic intraoperative test involving forward
      elevation with the elbow extended demonstrated entrapment of the tendon within
      the joint in each case. This test creates a characteristic "buckling" of the
      tendon and "squeezing" of the tendon between the humeral head and the glenoid
      ("hourglass test"). Excision of the tendon allowed immediate restoration of
      complete elevation. Mean Constant score increased from 38 points to 76 points
      postoperatively. DISCUSSION: The "hourglass biceps" is caused by a hypertrophic
      intraarticular portion of the tendon that is unable to slide into the bicipital
      groove during elevation of the arm. Loss of 10-20 degrees of passive elevation,
      bicipital groove tenderness, and radiographic findings of a hypertrophied tendon
      can aid in diagnosis. The "hourglass biceps" should not be misdiagnosed for a
      frozen shoulder. Definitive diagnosis is made at surgery with the "hourglass
      test": incarceration and squeezing of the tendon within the joint during forward
      elevation of the arm with the elbow extended. Simple tenotomy cannot resolve this
      mechanical block. Either tenotomy with excision of the intraarticular portion of
      the LHBT or tenodesis must be performed. The "Hourglass" biceps is an addition to
      the familiar pathologies of the long head of the biceps tendon (tenosynovitis,
      prerupture, rupture, instability), and should be considered in any case of
      chronic anterior shoulder pain associated with a loss of shoulder elevation.

PMID- 14726834
TI  - [Clinical and computed tomography results of 106 Latarjet-Patte procedures at
      mean 7.5 year follow-up].
AB  - PURPOSE OF THE STUDY: We reviewed, at a mean follow-up of 7.5 years, overall
      functional outcome, bony architecture of the humerus predisposing to anterior
      instability, and treatment failure after 106 Latarjet-Patte procedures performed
      in 102 patients (mean age 34 years). MATERIAL AND METHODS: The reproducibility of
      computed tomographic findings was validated prior to analysis. There were 5 men
      for 1 woman in this series. The initial injury, occurring at the age of 22 years
      on the average, was caused by trauma in 87% of the patients and generally
      involved the dominant upper limb. Ninety-seven patients practiced sports
      activities, a high risk sport for 48%. Clinical outcome was assessed with the
      Duplay score. Standard x-rays were also obtained, with bilateral computed
      tomography in 80 patients. RESULTS: The osteosynthesis screw had to be removed in
      6% of the cases due to posterior pain. The Latarjet-Patte procedure yielded 76.4%
      excellent or good results according to the Duplay scoring system. Sixty percent
      of the competition-level athletes like amateur athletes resumed their former
      sports activities at the same level. Seventy-percent of the patients were pain
      free. At last follow-up, complaints of pain, generally minor pain, were related
      to age of onset of instability, preoperative pain, and presence of joint
      degeneration. Loss of rotation was less than 11 degrees (mean). There was one
      case of recurrence subsequent to secondary trauma and 13.2% of the patients
      experienced residual apprehension. This lack of perfect stability was not related
      to a technical error but rather to a functional section of the head cartilage
      which remained in an overly anterior position because of a Malgaigne notch
      extending to the surface. Grade 2 or 3 joint degeneration was observed in 15% of
      the patients. It was related to duration of follow-up, patient age, mode of
      instability, and overlap of the bone block. Standard x-rays underestimated the
      incidence and degree of joint degeneration since the computed tomographic
      analysis revealed 17.5% of joint space narrowing (overall or posterior). Single
      cortex screwing led to nonunion, observed in 7% of the cases. Advanced osteolysis
      led to pain with altered overall function. DISCUSSION: Operated patients appear
      to have a constitutional morphology predisposing to anterior instability due to
      more marked bicipital lateralization than seen in controls. The differences
      concerning humeral version are less pronounced. There was a difference in
      version, independently of the presence of a notch, between the unstable and the
      healthy side. Conversely, in comparison with controls, a more anterior sector of
      the head cartilage (secondary anteversion) was only seen in patients with a
      notch. CONCLUSION: We consider that preoperative measurement of humeral
      retroversion and lateralization of the bicipital gutter can be helpful in
      establishing a precise therapeutic indication. Rather than searching for a
      constitutionally anomalous retroversion, we advocate searching for a more
      anterior functional section of the head cartilage (aggravated anteversion) caused
      by the presence of a Malgaigne notch on the unstable side (retroversion< or =0
      degrees ). When this anomaly is present, we prefer associating a derotation
      retroversing osteotomy of the humerus with the classical technique. This should
      avoid persistent residual apprehension.

PMID- 14726835
TI  - [Effect of anterior and posterior capsule release on elbow joint stability: an
      experimental study].
AB  - PURPOSE OF THE STUDY: The effect of the articular capsule on elbow stability is
      not well documented. Releasing the capsule might modify results of elbow
      arthrolysis, especially if it would lead to postoperative instability. The goal
      of the present study was to address the question in a cadaveric study. MATERIAL
      AND METHODS: Ten fresh cadaver elbows were studied. Anterior and posterior
      capsulectomy was performed. Lateral and medial collateral ligaments were
      preserved. Initially, the same operator tested the elbow joints manually in
      flexion-extension, valgus-varus, and pronosupination. The same joints were then
      tested with an experimental machine. RESULTS: Under these experimental
      conditions, no articular laxity was noticed in the coronal or sagittal planes
      after anterior and posterior isolated capsular release when the elbow joint was
      exposed to axial rotation, compression, or traction forces. Elbow laxity was
      observed only when lateral or medial ligaments were released. DISCUSSION:
      Anterior and posterior capsulectomy during elbow joint arthrolysis does not
      produce joint instability when the lateral and medial ligaments are preserved.

PMID- 14726836
TI  - [Long-term assessment of arthroscopic meniscus repair].
AB  - PURPOSE OF THE STUDY: A prospective study was set up to evaluate meniscal
      suturing using an inside-out technique. MATERIALS AND METHODS: Of an initial
      group of 20 patients who underwent closed meniscus repair between 1985 and 1988
      using an inside-out technique, 13 were studied. All patients were subjected to a
      clinical examination and an magnetic resonance imaging (MRI) investigation. The
      findings were compared with those of their previous follow-up examination (1994).
      The Hospital for Special Surgery (HSS) knee rating system was used. The study
      included 7 men and 6 women, ranging in age from 29 years to 50 years (mean age:
      35 years 6 months). The mean follow-up was 13 years 2 months (11 years 11 months
      15 years 4 months). Six left and 7 right knees were involved. Seven patients also
      had an anterior cruciate ligament (ACL) injury of which one was repaired 6 years
      after meniscal repair. RESULTS: All patients obtained an HSS score of more than
      75%. In all patients the site of the previous suture was still visible on MRI
      mainly by small metal artefacts in the meniscus. Patients with an unrepaired ACL
      lesion had an early onset of arthrosis and cartilage degeneration. CONCLUSION:
      Meniscal suturing gives good clinical long-term results. Magnetic resonance
      imaging, however, showed signs of mucoid degeneration or scar tissue in 46% of
      the patients.

PMID- 14726837
TI  - [Xenograft-related complications after filling valgus open wedge tibial osteotomy
      defects].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to assess clinical tolerance
      and radiological and histological changes observed after using a safe bovine
      xenograft (Lubboc) to fill open wedge defects after tibial osteotomy for
      valgisation in patients with medial femoro-tibial degeneration. MATERIAL AND
      METHODS: Thirty-one valgus open wedge tibial osteotomies were filled with a
      xenograft (Lubboc) and fixed with an epiphyseal plate in 16 women and 13 men,
      mean age 55 years two months. All patients had medial femorotibial degeneration
      with genu varum. Mean varus deviation was 6 degrees. RESULTS: At two years six
      months follow-up, five patients had developed a local complication: three cases
      of non-infected discharge and two infections. Among the other 26 cases, the
      radiographic evolution of the xenograft was similar to that described for
      autologous grafts but for seven cases, a lucent line persisted, isolating the
      graft. A biopsy was obtained in fifteen patients during the material removal
      procedure. Cell infiltration was absent in nine grafts. DISCUSSION: In light of
      the large number of local complications and the unpredictable nature of the
      radiological and histological outcome xenografting should be discontinued.

PMID- 14726838
TI  - [Prevention of venous thromboembolism after major orthopedic surgery: update and
      contribution of a specific synthetic inhibitor of factor Xa].
AB  - Despite widespread use of antithrombotic agents, major orthopedic surgery (total
      hip arthroplasty, major knee surgery, fracture of the femoral neck) still raises
      a high risk of deep vein thrombosis and pulmonary embolism. Proper understanding
      of thromboprophylaxis in orthopedic surgery requires good knowledge of the
      mechanisms of coagulation and the point of action of different antithrombotic
      agents. Sodium fondaparinux is the first synthetic inhibitor selective for factor
      Xa. It is composed of five saccharide units obtained by chemical synthesis, thus
      eliminating the risk of contamination by a pathogenic agent of animal origin and
      batch variability. Clinical trials using sodium fondaparinux for the prevention
      of venous thromboembolism after major orthopedic surgery have demonstrated its
      superiority over low-molecular-weight heparin without increased risk of
      clinically pertinent bleeding if the first injection is given at the proper time.
      We present the main results of clinical trials.

PMID- 14726839
TI  - [Sacroiliac fixation: a new technique after pelvic trauma].
AB  - We propose a new technique for sacroiliac fixation for the treatment of pelvic
      fracture with vertical and horizontal instability (Tile class C). This fixation
      technique allows control of vertical displacement while allowing, if needed, a
      certain degree of movement in the horizontal plane to facilitate reduction of
      anterior lesions. The technique involves insertion of two sacral screws, one in
      S1 and one in S2, and two iliac screws. The iliac screws are inserted in the
      posterior iliac crest through two sacroiliac connectors placed on a rod linking
      the two sacral screws. Vertical displacement is controlled by blocking the screw
      heads on the connecting rod. If needed, a certain degree of horizontal mobility
      of the half pelvis can be allowed by loosening the connectors on the rods. This
      technique was used for 4 patients. Anatomic reduction was achieved and no
      secondary movement of the osteosynthesis material nor secondary displacement were
      observed. The quality of the fixation allowed rapid weight bearing in the
      standing position and early walking without crutches. This type of fixation can
      only be used for type C12 fractures in the Tile classification.

PMID- 14726840
TI  - [Rare cause of acute carpal tunnel syndrome: acute metacarpal osteomyelitis].
AB  - Acute carpal tunnel syndrome resulting from acute metacarpal osteomyelitis is an
      exceptional etiopathogenic entity. A 6-year-old boy developed an acute carpal
      tunnel syndrome on the left four days after trauma. The carpal tunnel was opened
      in an emergency setting and exploration revealed a pale median nerve with
      infiltration of neighboring tissue. After release, pus issued from the depth of
      the tunnel. A posterior approach disclosed the collection and a total loss of the
      4th metacarpal periosteum, leading to the diagnosis of acute osteomyelitis. Edema
      and pain regressed rapidly with antibiotic therapy. A pathologic fracture of the
      4th metacarpal discovered three months later was treated conservatively. At 10
      months, the child has a very good functional result despite persistence of a
      short 4th metacarpal after healing. There was no motor or sensitive neurological
      deficit and thumb opposition was complete. We have been unable to find any other
      report of acute metacarpal osteomyelitis leading to acute carpal tunnel syndrome.
      Emergency treatment is crucial. Opening the annular ligament is the only way to
      achieve complete nerve recovery.

PMID- 14726841
TI  - [Neglected spontaneous bilateral rupture of the patellar tendon: a case report].
AB  - A patient taking corticosteroids for rheumatoid arthritis experienced a
      spontaneous bilateral rupture of the patellar tendon. Initially neglected, the
      rupture was repaired surgically by tendinoplasty using the semitendinous tendon
      for the right knee and inversion of the quadriceps tendon for the left.
      Functional results were similar. On the right knee, the wire cerclage loosened
      leading to posterior sagittal displacement of the patella, pointing out the
      difficulties encountered when repairing neglected rupture of the patellar tendon.
      Due to the small number of cases and difficulties in assessing the techniques
      proposed, no large-scale series has been reported in the literature.

PMID- 14726842
TI  - [Congenital absence of a cervical spine pedicle: misdiagnosis in a context of
      trauma].
AB  - Absence of a cervical spine pedicle is an exceptional congenital anomaly with a
      characteristic radiographic triad: i) absence of pedicle producing a pseudo
      enlargement of the homolateral foramen, ii) dysplastic aspect with posterior
      displacement of the homolateral facets and lamina, and iii) defect or absence of
      the homolateral transverse process. It is particularly important to recognize
      this radiographic picture in order to avoid misdiagnosis, e.g. unilateral
      fracture-displacement of the facet joints in a context of acute trauma, as
      occurred in our case, or pathological enlargement of the foramen (neurofibroma)
      without trauma. We describe the radiographic presentation of this congenital
      anomaly, stressing the importance of a homolateral oblique view and the
      usefulness of computed tomography for correct diagnosis.

PMID- 14726843
TI  - [Talectomy in adults].

PMID- 14726844
TI  - [Montgomery thyroplasty implant under local anesthesia for unilateral laryngeal
      paralysis].
AB  - OBJECTIVES: Based on an inception cohort of 63 patients with unilateral vocal
      fold paralysis consecutively treated with thyroplasty and Montgomery's implant
      under local anesthesia during the years 1997-2002, we recorded i) morbidity and
      mortality, ii) evolution of dysphonia and swallowing impairment and iii) a
      prospective analysis of selected speech and voice parameters in an attempt to
      determine their evolution during the first 12 postoperative months and to search
      for potential statistical relationships with the following variables (age,
      gender, side of the paralysis, etiology of the paralysis, time between onset of
      paralysis and thyroplasty, position of the paralyzed true vocal fold, nerve
      involved, associated pneumonectomy, prior intracordal injection of autologous fat
      and surgeon). RESULTS: The overall complication rate was 8%. Minor complications
      occurred in 6.5% of the patients and included 4 cases of laryngeal edema
      successfully treated with oral steroids. Major complications occurred in 1.5% of
      the patients. Intralaryngeal hematoma requiring temporary tracheotomy was the
      major complication. Swallowing was improved in 93.5% of the patients. Immediate
      improvement of speech and voice was noted in all. Secondary degradation of speech
      and voice occurred in one patient. At revision thyroplasty lateral displacement
      of the implant was noted and successfully repositioned. At one month post
      operatively, the values of maximum phonation time, speech rate, group phrasing
      standard deviation of the fundamental frequency, jitter and shimmer were
      statistically improved while the fundamental frequency did not vary
      significantly. At 12 months post-operatively the noise to harmonic ratio was
      improved while the other parameters remained stable. No significant statistical
      relationship was found between the post-operative speech and voice parameters and
      the variables under analysis. CONCLUSION: Based on the current series and a
      review of the medical literature, thyroplasty with Montgomery's implant under
      local anesthesia appears to be an easy, effective and safe procedure that might
      be used in all patients with unilateral laryngeal nerve paralysis.

PMID- 14726846
TI  - [Comparison of laryngoscopy and CT-scan results before partial laryngectomy].
AB  - OBJECTIVES: Careful assessment of tumor extension is required before partial
      laryngectomy in order to ensure optimal carcinological safety. Laryngoscopy and
      CT-scan constitute the explorations of reference. We investigated the value of
      these two examinations and their association for the evaluation of glottic and
      supraglottic tumors. METHOD: We compared laryngoscopy and CT findings with those
      of the pathologic examination of the surgical specimen in a retrospective study
      of 57 patients. RESULTS: The results were presented by T-staging, then as a
      function of the laryngeal floor of the tumor and the anatomic localization. The
      laryngoscopy findings were most contributive for small tumors. Large spaces are
      better examined with the scanner. CONCLUSION: This study showed that the
      performance of laryngoscopy and CT-scan for the assessment of glottic and
      supraglottic tumors can be improved by a better knowledge of the limitations of
      each type of explorations for this type of assessment. CT-scan currently provides
      a better topographic assessment of the tumor than endoscopy; even higher
      performance can be expected with the advent of technological advances.

PMID- 14726845
TI  - [Nonrecurrent inferior laryngeal nerve: review of 13 cases].
AB  - OBJECTIVE: This study reviews a rare and poorly understood anatomic anomaly of
      the thyroid region: non-recurrence of the inferior laryngeal nerve. METHOD: We
      describe thirteen cases of non-recurrence of the laryngeal nerve observed during
      2128 surgical procedures on the thyroid gland. RESULTS: The malformation was
      right-sided in all thirteen patients (11 women, 2 men) and occurred at a
      frequency of 0.4% of all of the nerves explored. Only two complications were
      noted in this series of 13 cases: one case of temporary paresis and one case of
      irreversible vocal cord paralysis. CONCLUSION: A rare although not exceptional
      occurrence, non-recurrence of the inferior laryngeal nerve is an anomaly that
      Head and Neck surgeons should be familiar with so as to avoid nerve damage that
      can result in irreversible vocal cord paralysis.

PMID- 14726847
TI  - [Nasal polyposis: quantification of the eosinophil and granulocyte infiltrates.
      Anatomo-clinical correlations].
AB  - OBJECTIVE: Prospective study designed to count the number of granulocytic cells
      and eosinophils in nasal polyp tissue removed during ethmoidectomy and to look
      for anatomical correlations. METHODS: Bilateral ethmoidectomy with a
      postoperative local steroid treatment was performed in 40 patients with nasal
      polyposis. Immunolabeling of the operative specimen using common leukocyte
      antigen (CD 45) and granulocytes associated antigen (CD 15) and quantification of
      the granulocyte infiltrate by image and manual counting of eosinophils with the
      mean of micro-reticule, were performed. The results were compared to those of 10
      healthy subjects. An endoscopy of the postoperative cavities was performed one
      year after surgery to assess the local results. RESULTS: The granulocyte and
      eosinophil infiltrates were significantly more important in the operated patients
      compared to the healthy population (p<10(- 4)). A "moderate" granulocytic
      infiltration (G -) was found in 11 patients out of 40 (27.5%). Among them, 9
      patients showed less than 30% eosinophils (mean 16.2% +/- 2%). "Severe"
      granulocytic infiltrate (G +) was found in 29 patients out of 40 (72.5%). Among
      them, 25 patients showed more than 30% eosinophils (mean 48.8% +/- 2%). Most of
      the patients with G + type infiltrate suffered from asthma or Widal disease. One
      year after surgery, 17 out of 29 G + patients had no nasal polyposis recurrence,
      12 out of 29 G + patients had a recurrence. However, 12 out of 15 patients with
      recurrent polyposis had G + type infiltrate. CONCLUSIONS: Granulocyte and
      eosinophil infiltration cannot be considered as a prognostic factor for
      recurrence at the time of surgery. A severe granulocyte and eosinophil
      infiltration is a typical feature of nasal polyposis, particularly in patients
      with asthma and/or in the aspirin triad.

PMID- 14726848
TI  - [Nystagmus and vibratory test: evidence for mechanism. Material conditions and
      methods in the fast detection of unilateral vestibular lesions].
AB  - OBJECTIVE: The aim of the present study was to examine the characteristics of
      vibratory nystagmus (VN), optimise the topography and the frequency of the
      stimulus, determine the origin of the VN and analyze its clinical implications.
      MATERIAL AND METHOD: Fifty-two severe unilateral vestibular lesions (SUVL) (post
      surgical vestibular areflexy) were studied. The vibratory nystagmus was measured
      by 2D and 3D videonystagmography (Synapsis, France). The stimulus was applied
      with a 3S vibrator at the vertex, both mastoids, and posterior cervical muscles,
      at frequencies ranging from 20 to 150 Hz. For topographic optimization,
      stimulation was given with S vibrator (Synapsis, France) at 100 Hz. The
      interferences between the vibratory test (VT) and the caloric test (CT) were
      studied on the normal ear (in 11 subjects). The same study was carried out with
      the optokinetic test. RESULTS: The VT revealed a defective nystagmus at all
      frequencies of stimulation. Optimal response was obtained in a band frequency of
      80-120 Hz. Stimulations at 100 Hz showed optimal responses for mastoid topography
      (responses in 96% of the cases). Stimulation at the posterior cervical muscles
      and at the vertex indicated respectively a response in 90% and 60% of the cases.
      The efficiency of the mastoid stimulation was not correlated with the side of
      stimulation (p=0.9). The interference between the VT and caloric test (CT) with
      cold water (30 degrees C and 20 degrees C) exhibited the inversion of the caloric
      nystagmus during the vibrator stimulation. The resulting nystagmus was
      respectively an algebraic subtraction or addition between the pre-existing
      caloric nystagmus and the value of the vibratory nystagmus obtained before the
      caloric test. Adaptation of the VN was moderate. The interference between the VT
      and the optokinetic test resulted in a subtraction or addition effect, according
      to the side of the lesion and the direction of the optokinetic stimulus.
      CONCLUSION: The VT is an efficient stimulation in mastoid topography. The
      vestibular contribution is bilateral by bony conduction of the vibration, it
      explores frequencies ranging from 30 to 120 Hz, with a maximum of response at 100
      Hz. The VT interacts with the caloric test and the optokinetic test. The
      stimulation is very strong, and is able to inverse the caloric nystagmus at cold
      water stimulation (20 degrees C) In labyrinthine-defective subjects, the VN is
      always defective at all frequencies, whatever the topographic location of the
      stimulus, and the position of the head.

PMID- 14726849
TI  - [Ethmoid adenocarcinoma: a series of 17 cases].
AB  - INTRODUCTION: Ethmoid adenocarcinoma are and represent rare, 2.5 to 3% of head
      and neck cancers. The 5-year survival is around 50% for all stages. We present a
      series of 17 patients treated in our institution. OBJECTIVES: Expose the
      treatment of these patients and evaluate the results. METHODS: A retrospective
      study of 17 consecutive patients, treated between 1992 and 1999 for an ethmoid
      adenocarcinoma (15 T4 and 2 T2) and evaluated in 2002, with a mean follow-up of
      5.8 years. RESULTS: In May 2002, 4 (23.53%) patients were alive and disease-free,
      3 (17.65%) were alive with recurrence and 10 (58.82%) was died. The 5-year
      survival with Kaplan Meyer method is 41%. CONCLUSION: This series demonstrates
      the contribution of a combined approach for T3 and T4 tumors. The bifrontal
      approach induced an important morbidity in our series and should be replaced by
      the nasofrontal approach. Most teams agree that postoperative radiotherapy is
      necessary but the appropriateness of chemotherapy is still discussed. Some
      authors are of the opinion that it has no action on adenocarcinoma and others
      that it improves survival. It seems to have been efficient in our T4 patients.

PMID- 14726850
TI  - [Parotid haemangioma: MR imaging findings in 3 cases].
AB  - OBJECTIVE: Parotid gland hemangioma is uncommon in infancy and childhood and even
      rarer in adulthood. The clinical presentation, supported by imaging findings
      provides the diagnosis. The aim of this work is to discuss the different clinical
      and radiological aspects of this lesion with a special emphasis on MRI findings.
      METHODS: Three patients with unilateral hemangioma are presented. Radiological
      investigations including ultrasound and magnetic resonance imaging (1 Tesla) were
      performed. RESULTS: Sonographic studies showed a lobulated mass with intermediate
      echogenicity, enlarging most or all of the visualized parotid gland. Correlative
      MR images in all cases showed a well-defined mass with an intermediate signal on
      T1-weighted images. On T2-weighted images, all masses appeared bright,
      heterogeneous with low signals within the masses consistent with flow voids
      representing blood vessels. Phleboliths were present in one case. CONCLUSION: MRI
      is the investigation of choice allowing an accurate diagnosis and avoiding
      invasive procedures including biopsy.

PMID- 14726851
TI  - [Rosai-Dorfman disease with orbital and rhinopharyngeal localizations. A case
      report].
AB  - OBJECTIVES: We present a case report of Rosai-Dorfman disease with multiple
      extranodal involvement and favorable outcome after steroid therapy. MATERIAL AND
      METHODS: Rosai-Dorfman disease was diagnosed in a 17-year-old man with orbital,
      lacrymal, and rhinopharyngeal localizations. Histopathologic examination of
      lymphadenopathy biopsy revealed the diagnostic of Rosai-Dorfman disease. We
      present the histological findings leading to diagnosis and radiological data.
      RESULTS: Conservative treatment with oral steroids resulted in the resolution of
      cervical lymphadenopathy and extranodal lesions. The patient was free of problems
      nine mouths after discontinuation of his treatment, demonstrating its efficacy
      and safety. CONCLUSION: Rosai-Dorfman disease is a benign disorder and steroid
      treatment must be initiated in cases with significant cosmetic deformity.

PMID- 14726852
TI  - LASIK and its alternatives: an update.

PMID- 14726853
TI  - Zolmitriptan (Zomig) nasal spray for migraine.

PMID- 14726854
TI  - Tissue and tumor mosaicism of the myotonin protein kinase gene trinucleotide
      repeat in a patient with multiple basal cell carcinomas associated with myotonic
      dystrophy.
AB  - We describe the third case (to our knowledge) of multiple basal cell carcinoma
      associated with myotonic dystrophy and carry out a genetic study of the tumor
      comparing it with healthy skin. We consider that our results show that this
      association might be not a purely random phenomenon and that the particular
      genetic characteristics of this disorder might have a role in the pathogenesis of
      the tumor.

PMID- 14726855
TI  - Granulomatous slack skin without evidence of a clonal T-cell proliferation.
AB  - Granulomatous slack skin is a rare cutaneous disorder with less than 50 cases
      presented in the English-language literature. The disease is characterized by
      circumscribed erythematous lax skin accentuated most commonly in the axillary and
      inguinal areas. A strong association with a preceding or evolving diagnosis of
      mycosis fungoides or Hodgkin's disease has been reported. Previous reports
      describe the entity as a lymphoproliferative disease in the same spectrum as
      mycosis fungoides and Hodgkin's disease with a monoclonal T-cell population. Our
      case, without an evident beta-T-cell receptor rearrangement, suggests that not
      all cases of granulomatous slack skin are a result of an indolent lymphoma.
      Granulomatous slack skin probably represents a spectrum of diseases that can
      eventuate into a lymphoproliferative process.

PMID- 14726856
TI  - Cutaneous true histiocytic malignancy: true histiocytic lymphoma.
AB  - True histiocytic malignancies (THM) are controversial disorders that are being re
      evaluated with modern cellular and molecular biology techniques. True histiocytic
      lymphoma (THL) is a low-incidence, poor-prognosis THM. It mainly affects the
      skin, gastrointestinal tract, and bone tissues. Occasionally, skin lesions are
      the presenting clinical features. A patient with initially cutaneous THL is
      described. This and other reported cases confirm that THM are a nosologic entity
      by themselves.

PMID- 14726857
TI  - Multiple accessory tragi as a clue to the diagnosis of the oculo-auriculo
      vertebral (Goldenhar) syndrome.
AB  - We present a newborn with multiple features of the oculo-auriculo-vertebral
      spectrum (OAVS), or Goldenhar's syndrome. Although not reported previously,
      aplasia cutis congenita might be within the spectrum of anomalies seen in the
      syndrome. Of particular importance to the dermatologist is the finding of
      multiple accessory tragi in a linear distribution from the preauricular skin,
      along the mandible, to the lateral neck, which might be a clue to the diagnosis
      of OAVS. This syndrome is associated with additional systemic anomalies that can
      often be found by simple screening techniques.

PMID- 14726858
TI  - Subcutaneous and cerebral cysticercosis.
AB  - Cysticercosis is a human infestation, which is considered the most common cause
      of seizures worldwide. The subcutaneous lesions can help in the diagnosis of
      neurocysticercosis. We describe a case of a 45-year-old patient with multiple
      cutaneous nodules first seen 2 years ago that were increasing in number, and
      normal neurologic and fundoscopic examination. Neurologic symptoms started 3
      months before hospital admission as a mild headache and muscular weakness. The
      imaging examinations showed a massive central nervous system involvement.
      Physicians must be aware of the importance of subcutaneous nodule examination for
      the diagnosis of neurocysticercosis.

PMID- 14726859
TI  - Subcutaneous panniculitic T-cell lymphoma in children: response to combination
      therapy with cyclosporine and chemotherapy.
AB  - We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules
      and fever. Extensive evaluation, including several biopsy specimens, led to a
      diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in
      children. Both patients were treated with oral cyclosporine in an effort to
      suppress the cytokine release from T-cells that has been thought to induce the
      hemophagocytic syndrome. The patients responded dramatically to cyclosporine
      treatment with defervescence of the fever and reduction in number and size of the
      subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved
      complete remission in the first patient. This report suggests the value of
      cyclosporine as a first-line agent coupled with chemotherapy in the treatment of
      patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic
      review of 8 described pediatric cases of subcutaneous panniculitic T-cell
      lymphoma is also presented.

PMID- 14726860
TI  - Neonate with a fibrosarcoma and consumptive coagulopathy.
AB  - We report a case of a neonate with a congenital tumor on the left palm. The
      patient had a grapefruit-sized tumor and coagulopathy at birth and was presumed
      to have a hemangioendothelioma with associated Kasabach-Merritt phenomenon. When
      the tumor failed to respond to systemic steroids, a biopsy specimen was taken,
      revealing a fibrosarcoma. We describe this case to highlight the importance of
      including rare tumors, such as fibrosarcomas, in the clinical differential when
      evaluating a congenital tumor with associated coagulopathy. We discuss subtle
      differences in clinical presentations that might aid in differentiating vascular
      tumors from fibrosarcomas.

PMID- 14726861
TI  - Furuncular myiasis caused by Dermatobia hominis, the human botfly.
AB  - Myiasis is a common travel-associated dermatosis. Travelers to many parts of
      Central and South America are susceptible to infestation by Dermatobia hominis.
      Despite the common name of human botfly, D hominis infests a broad range of
      mammals and is a severe pest to economically important farm animals in endemic
      regions. The adult female does not lay the eggs on the host. Instead, the adult
      female infests hosts indirectly by using blood-feeding arthropods to serve as
      phoretic vectors to transport the eggs. We present a patient who acquired
      Dermatobia when bitten by a day-active mosquito during a visit to Guatemala. He
      had a locally painful, firm furuncular lesion with a central pore that drained
      serosanguineous exudates. The patient applied an occlusive ointment and recovered
      the larva after it emerged. In this report we discuss the life cycle of D
      hominis, the differential diagnosis, and therapeutic approaches.

PMID- 14726862
TI  - Isomorphic response after saphenectomy in a patient with granuloma annulare.
AB  - Physical trauma has been reported as an etiologic factor of granuloma annulare,
      resembling a Koebner phenomenon. Moreover, granuloma annulare frequently arises
      at the same location of a previously healed, unrelated skin disease, mainly
      herpetic infection. These data seem to suggest that granuloma annulare might be a
      peculiar pattern of skin reaction to different stimuli, either physical or
      biologic, in predisposed subjects. In the case reported herein, the onset of a
      typical lesion of granuloma annulare at the site of saphenectomy might be
      explained as the result of an aberrant wound healing process, with release, by
      keratinocytes and/or Langerhans cells, of lymphocyte-derived chemotactic
      cytokines, capable of promoting the development of the granulomatous lesion.

PMID- 14726863
TI  - CHILD syndrome avant la lettre.
AB  - The CHILD syndrome is an acronymic designation for congenital hemidysplasia with
      ichthyosiform nevus and limb defects. This X-linked dominant, male-lethal trait
      is caused by mutations in the gene NSDHL that is localized at Xq28 and involved
      in cholesterol metabolism. The CHILD nevus that constitutes a hallmark of this
      multisystem birth defect usually shows a striking lateralization pattern. Until
      now, a report of Zellweger and Uehlinger from 1948 was believed to represent the
      first published case of CHILD syndrome. However, we have now found an earlier
      report published in 1903 by Otto Sachs. An 8-year-old girl had a "xanthoma-like
      nevus" involving the right axillary region and a congenital muscular weakness of
      the right upper arm. Sachs described the clinical and histopathological features
      of CHILD nevus comprehensively, including the characteristic changes of
      verruciform xanthoma that can be taken within the group of epidermal nevi as a
      pathognomonic feature of CHILD nevus. This report is the earliest description of
      CHILD syndrome known so far. Moreover, Sachs presented in this article a
      comprehensive description of verruciform xanthoma, thus anticipating Shafer's
      "first report" of this histopathological phenomenon (1971) by almost 70 years.

PMID- 14726864
TI  - Fatal granulomatous amebic encephalitis caused by Balamuthia mandrillaris
      presenting as a skin lesion.
AB  - Granulomatous amebic encephalitis is an uncommon central nervous system (CNS)
      infection, usually caused by Acanthamoeba spp., which generally occurs in
      immunocompromised individuals. Balamuthia mandrillaris is a recently described
      free-living ameba that occasionally causes fatal CNS disease. The infection might
      start from a minor, slowly progressive, skin ulceration that can be present for
      weeks to months before neurologic changes occur. The clinical and histologic
      presentation is easily confused with many other diseases. Accurate diagnosis
      requires an awareness of this unusual presentation of amebiasis and
      identification of the amebic trophozoites in tissue and culture. Special stains
      are helpful, but immunofluorescence assays or electron microscopy is required to
      identify the organism as B mandrillaris. We present a fatal case of granulomatous
      amebic encephalitis that began as a cutaneous infection in an immunocompetent
      host.

PMID- 14726865
TI  - The chilblain-like eruption as a diagnostic clue to the blast crisis of chronic
      myelocytic leukemia.
AB  - A 70-year-old Japanese man visited our clinic with the chief complaint of
      chilblain-like eruptions on the toes of both feet. His toes were bluish,
      erythematous, and swollen. Neither oral administration of vitamin E for 2 weeks
      nor wearing insulated socks improved the clinical manifestations. Peripheral
      blood examination revealed the presence of a large number of monocytic atypical
      cells and myeloblasts, anemia, and thrombocytopenia. In the bone marrow,
      monocytic cells were elevated, and myelocytic atypical cells were observed.
      Chromosomal analysis demonstrated Philadelphia chromosome. We diagnosed him as
      having a blast crisis of chronic myelocytic leukemia (CML). A biopsy specimen of
      the skin from the chilblain-like eruption showed infiltration of large, atypical,
      mononuclear cells; most of them were positive for CD68, and some of them were
      positive for CD14. Therefore, we concluded that the chilblain-like eruptions on
      his toes were specific skin lesions of a blast crisis in CML.

PMID- 14726866
TI  - Incontinentia pigmenti with painful subungual tumors: a two-generation study.
AB  - We report 2 cases of painful subungual dyskeratotic tumors occurring in a mother
      and daughter with incontinentia pigmenti (IP) as a late manifestation of the
      disease. Both patients had a history of similar lesions appearing over a period
      of years on the digits of both the hands and feet. Biopsy specimens of the
      current lesions were examined and compared with the previous material available
      on both patients. The current tumors and the earlier lesions (the latter of which
      had originally been given diagnoses that included squamous cell carcinoma,
      keratoacanthoma, and verruca vulgaris) showed similar histopathologic features
      that were consistent with the late (verrucous) stage of IP. To our knowledge,
      this is the first reported case of numerous subungual tumors in IP involving more
      than 1 generation in the same family; the first report of subungual tumors in IP
      to include a 16-year follow-up; and the first report of a probable recurrence of
      subungual tumors in IP at the same site of a previously surgically removed tumor.

PMID- 14726867
TI  - Progressive multilayered banded skin in Winchester syndrome.
AB  - Winchester syndrome is a rare genetic disorder, one of the inherited osteolysis
      disorders which are a group of diseases characterized by destruction and
      resorption of affected bones with consequent skeletal deformities and functional
      impairment. The syndrome is characterized by dissolution of carpal and tarsal
      bones with generalized osteoporosis, progressive joint contractures, short
      stature, peripheral corneal opacities, and coarse facial features, though there
      is variability within the clinical features. Phenotypic heterogeneity of
      cutaneous features are also reported to date of diffusely thickened leathery
      skin, hypertrichosis, patches of hyperpigmented, hypertrichotic leathery skin in
      annular or linear distribution, widespread acne, subcutaneous nodules, and
      gingival hypertrophy. We describe widespread progressive multilayered symmetrical
      restrictive banding of the skin developing in a woman with Winchester syndrome
      during her mid-twenties.

PMID- 14726868
TI  - Juvenile spring eruption: clinicopathologic features and phototesting results in
      4 cases.
AB  - Juvenile spring eruption is a distinct photodermatosis characterized by the
      development of papules and vesicles on light-exposed areas of the ears usually in
      the early springtime. It primarily affects boys and young men, and has a tendency
      to occur in the form of small epidemics. We report a similar outbreak in separate
      groups of soldiers who were performing military exercises during cold and sunny
      weather of a midwinter season. The clinicopathologic features and phototesting
      results are described in 4 of these cases. All patients showed normal erythemal
      responses to monochromator phototesting with UV and visible wave bands.
      Photoprovative testing with repeated daily exposures of the ears to a broadband
      UVA source provoked diffuse erythema and itching in 1 case, whereas similar
      photoprovocation of a nonaffected area, ie, the flexor surface of the forearm, in
      2 patients did not yield a skin reaction. Although the cause of juvenile spring
      eruption is not known, our observations further strengthen the hypothesis that
      the disorder is a localized variant of polymorphous light eruption.

PMID- 14726869
TI  - Infantile systemic hyalinosis.
AB  - Infantile systemic hyaloinosis is a rare, progressive, and fatal disease that is
      inherited in an autosomal recessive fashion. We describe 2 patients in whom
      thickened skin; small nodules of the perianal region, face, and neck; joint
      contractures; growth failure; diarrhea; and frequent infections developed within
      the first few weeks of life. Both patients died before 2 years of age.

PMID- 14726870
TI  - Laser surgery: an approach to the pediatric patient.
AB  - Revolutionary advances in laser research and technology have led to expanded
      dermatologic laser applications. With the wide range of lasers now available, a
      large spectrum of skin conditions in the pediatric population can be successfully
      treated or, in some cases, completely eradicated. Laser treatment of the
      pediatric population poses a unique challenge for the clinician on a variety of
      levels. Physically, the composition of many vascular and pigmented lesions
      changes as children age making them more resistant to laser therapy. Thus, in
      many cases, treating lesions at an early age has resulted in clearing in fewer
      sessions and with decreased complications. Mechanically, lasers and laser
      settings used for the treatment of adult lesions may have to be adjusted for the
      smaller vessels and the unpredictable nature of scarring with children's skin.
      For vascular lesions, the pulsed dye laser is considered the laser of choice for
      its efficacy and low-risk profile, whereas the Q-switched, pigment-specific
      lasers are ideal for most childhood pigmented lesions, allowing for single
      pigment cell destruction. Other conditions such as acne and acne scars,
      psoriasis, keloids, warts and hypertrichosis that traditionally have been treated
      with a variety of modalities are now being managed safely with laser surgery.
      Other issues specific to the pediatric population include the determination of
      suitable anesthesia, the provision of size-appropriate safety equipment, and the
      assessment and management of patient and parent anxiety. The use of lasers
      specifically designed for structural differences in pediatric lesions and the
      recognition of emotional issues surrounding a young patient during laser surgery
      are critical components of successful treatment. LEARNING OBJECTIVE: At the
      conclusion of this learning activity, participants should be familiar with the
      mechanism of laser technology, current trends in the use of lasers for skin
      lesions in the pediatric population, and the issues specific to treating a
      patient with laser surgery.

PMID- 14726872
TI  - Nail disorders in hemodialysis patients and renal transplant recipients: a case
      control study.
AB  - BACKGROUND: There is one published case-control study of nail disorders in
      hemodialysis patients. The nail changes that occur in renal transplant recipients
      have not been investigated specifically. OBJECTIVE: The aim of this study was to
      determine prevalence rates of nail disorders in hemodialysis patients and renal
      transplant recipients, and to investigate whether these nail pathologies are
      related to hemodialysis and renal transplantation. METHODS: One hundred and
      eighty-two hemodialysis patients and 205 renal transplant recipients were
      screened for the presence of nail disorders. The findings in these groups were
      compared with findings in 143 healthy individuals. RESULTS: One hundred and
      twenty-seven patients (69.8%) in the hemodialysis group and 116 patients (56.6%)
      in the renal transplant recipients had at least one type of nail pathology.
      Absence of lunula, splinter hemorrhage, and half-and-half nails were
      significantly more common in the hemodialysis patients than in the renal
      transplant recipients. Leukonychia was significantly more frequent in the renal
      transplant recipients than in the hemodialysis patients and controls. CONCLUSION:
      Hemodialysis patients and renal transplant recipients have higher rates of nail
      disease than the healthy population. Renal transplantation may reduce the
      frequencies of splinter hemorrhage and half-and-half nails. Interestingly,
      leukonychia increases significantly after renal transplantation.

PMID- 14726871
TI  - Acitretin treatment in (pre)malignant skin disorders of renal transplant
      recipients: Histologic and immunohistochemical effects.
AB  - BACKGROUND: The incidence of (pre)malignant skin lesions after renal
      transplantation is high. Acitretin treatment appears to decrease the number of
      new squamous cell carcinomas and ameliorates the aspect and reduces the number of
      actinic keratoses. However, no histologic and immunohistochemical studies have
      been performed to further substantiate these observations. METHODS: In 33 renal
      transplant recipients, biopsies were taken before and after 3 months of treatment
      with acitretin in doses up to 0.4 mg/kg/day. Histologic and immunohistochemical
      parameters for dysplasia, epidermal thickness, proliferation, differentiation,
      apoptosis, and dermal inflammation were analyzed. RESULTS: Following acitretin
      treatment, a significant reduction in epidermal thickness (P =.002) and a
      significant increase in normal differentiation parameter K10 (P =.02) was
      observed. Epidermal proliferation did not change, nor did apoptosis,
      inflammation, keratinocytic epidermal neoplasia score, or transglutaminase
      staining. At baseline, in 8 actinic keratoses, a single cell expression pattern
      of K13 and/or K19 was found. This was associated with high levels of parameters
      indicative of high-risk lesions (P <.05). After acitretin treatment, an increase
      in K13 (P =.006) and K19 (P =.05) was found, together with a change in expression
      towards a focal or band-like staining pattern. CONCLUSION: Acitretin improves the
      aspect of actinic keratoses via alteration of keratinization, resulting in
      peeling of the stratum corneum. No significant change in proliferation was found,
      which may explain the rapid recurrence of actinic keratoses seen after cessation
      of acitretin treatment.

PMID- 14726873
TI  - Osteoarticular complications of erysipelas.
AB  - BACKGROUND: Rare osteoarticular complications occurring after erysipelas have
      been reported. We describe 9 patients in whom various osteoarticular
      complications developed during erysipelas. OBJECTIVE: We sought to analyze
      osteoarticular complications during erysipelas, paying special attention to
      clinical, bacteriologic, and radiologic data. METHODS: Data were retrospectively
      recorded from the files of patients seen in 3 dermatologic centers between 1998
      and 2000. They included laboratory tests, bacteriologic cultures, radiologic
      investigations, and treatment modalities and outcome of both erysipelas and
      osteoarticular complications. RESULTS: We observed 9 patients (7 men and 2 women;
      mean age 49.6 years) who first presented with typical erysipelas of the lower
      limb and then osteoarticular complications developed during the course of their
      disease, always localized to a joint contiguous to the erysipelas plaque. These
      complications included: relatively benign complications, ie, bursitis (n = 5) or
      algodystrophy (n = 1), occurring after erysipelas with favorable course; and more
      severe complications, ie, osteitis (n = 1), arthritis (n = 1), and septic
      tendinitis (n = 1), occurring after erysipelas characterized by local cutaneous
      complications (abscess, necrosis). CONCLUSIONS: Osteoarticular complications of
      erysipelas can be divided into the 2 groups of nonseptic complications (mainly
      bursitis), which are characterized by a favorable outcome, and septic
      complications (osteitis, arthritis, tendinitis), which require specific, often
      prolonged treatment and, sometimes, operation. Their diagnosis is on the basis of
      clinical and radiologic findings rather than joint aspirations, which are usually
      not possible through infected skin tissue.

PMID- 14726874
TI  - Calcinosis of the cutis and subcutis: an unusual nonimmunologic adverse reaction
      to subcutaneous injections of low-molecular-weight calcium-containing heparins.
AB  - BACKGROUND: Local side effects at the injection sites of low-molecular-weight
      heparins are rare and can be of immunologic or nonimmunologic origin. Calcinosis
      cutis is a rare disorder and occurs in various circumstances. In patients with
      chronic renal failure the risk of pathologic calcifications is raised due to
      elevated calcium-phosphorus products. OBJECTIVE: Five patients suffering from
      renal failure developed remarkable cutaneous and subcutaneous nodules or plaques
      following subcutaneous nadroparin-calcium injections. Our aim was to evaluate the
      morphology and precipitation factors of these calcifications and to discuss
      immunological and nonimmunological differential diagnoses. METHODS: Histological
      examination, spectroscopic analysis, ultrasonography, allergy testing and
      reexposition testing including non-calcium heparins were performed. RESULTS:
      Histology using the van Kossa staining technique revealed calcinosis of the
      dermis and subcutis. Ultrasonography showed focal subcutaneous calcifications. In
      all patients the calcium-phosphorus products were elevated. CONCLUSION:
      Clinicians should be aware that patients with renal failure and elevated calcium
      phosphorus products may be at risk of developing calcinosis cutis at calcium
      containing heparin injection sites. As a consequence, we propose the use of non
      calcium heparins in these patients.

PMID- 14726875
TI  - Photoallergic contact dermatitis from ketoprofen induced by drug-contaminated
      personal objects.
AB  - BACKGROUND: Photoallergic contact dermatitis from ketoprofen has been recognized
      since the mid-1980s. Skin reactions have been reported to continue weeks after
      discontinuation of ketoprofen. One reason for this could be residual ketoprofen
      in the skin, which has been shown in a skin biopsy specimen. OBJECTIVE: We sought
      to report on 3 cases of photoallergic contact dermatitis from ketoprofen in
      topical anti-inflammatory gels and on relapses of dermatitis appearing after use
      of ketoprofen-contaminated objects. METHODS: We patch and photopatch tested, with
      standard series, the anti-inflammatory gel, ketoprofen, and its ingredients in
      serial dilutions and extracts of personal objects. We performed chemical
      investigations of personal objects with thin-layer chromatography, high-pressure
      liquid chromatography, and gas chromatography-mass spectrometry. RESULTS:
      Photoallergy was demonstrated to ketoprofen, which was detected in personal
      objects. CONCLUSION: Relapses of photoallergic contact dermatitis in patients
      photoallergic to ketoprofen can be induced by ketoprofen-contaminated objects
      such as bandages and slippers.

PMID- 14726876
TI  - Reflectance confocal microscopy may differentiate acute allergic and irritant
      contact dermatitis in vivo.
AB  - BACKGROUND: Acute irritant contact dermatitis (ICD) and allergic contact
      dermatitis (ACD) may be difficult to distinguish by clinical or histologic
      assessment. Reflectance confocal microscopy (RCM) enables real-time, high
      resolution skin imaging in vivo. OBJECTIVE: We sought to image, characterize, and
      distinguish acute ACD and ICD in vivo. METHODS: Volunteers with ACD were patch
      tested with an allergen and the irritant, sodium lauryl sulfate. RCM imaging and
      transepidermal water loss measurements were performed at 24 and 72 hours. Biopsy
      specimens were correlated with RCM images. RESULTS: Spongiosis, epidermal
      inflammatory cell infiltrate, and vesicle formation were observed in ACD and ICD.
      Compared with ACD, ICD showed greater disruption of the stratum corneum, and more
      parakeratosis. There was a significantly greater increase in transepidermal water
      loss for ICD compared with ACD. CONCLUSION: RCM is a promising tool for dynamic,
      noninvasive assessment and may help to differentiate acute ACD and sodium lauryl
      sulfate-induced ICD.

PMID- 14726877
TI  - Modulation of linear nail growth to treat diseases of the nail.
AB  - Diseases affecting the nail can cause significant distress and interfere with an
      individual's self-esteem, personal relationships, and professional life. Often,
      hand and foot function is adversely affected. Certain diseases are characterized
      by accelerated nail growth while others show a decrease. In this review, drugs
      known to influence the growth rate of nails are examined, highlighting their
      potential use as adjunctive therapy in the treatment of nail disease. This
      approach, described recently in the context of the yellow nail syndrome,(1) may
      be extended to other common disorders such as nail psoriasis, brittle nails, and
      onychomycosis.

PMID- 14726879
TI  - Treatment of psoriatic arthritis with granulocyte and monocyte adsorption
      apheresis.
AB  - Granulocyte and monocyte adsorption apheresis (GCAP) is a new extracorporeal
      apheresis treatment modality that removes pathogenic granulocytes. Recently, we
      found that GCAP is useful for treating pyoderma gangrenosum and pustular
      psoriasis. We thought that this treatment may also be effective for treating
      other disorders attributable to activated granulocytes and studied the efficacy
      of GCAP in 4 patients with psoriatic arthritis. Treatment with GCAP resulted in
      remarkable clearing of joint pain, suggesting that GCAP is valuable for treating
      arthritis as well as skin disorders. We present a detailed description of these
      patients and this novel therapy.

PMID- 14726878
TI  - Treatment of cutaneous sarcoidosis with thalidomide.
AB  - BACKGROUND: Although systemic corticosteroids are effective against cutaneous
      sarcoidosis, alternative therapies are needed. OBJECTIVE: We sought to assess the
      efficacy and tolerance of thalidomide for cutaneous sarcoidosis. METHODS: We
      performed a retrospective evaluation of thalidomide (100-200 mg/d) in 12
      consecutive patients with cutaneous sarcoidosis treated in a university hospital
      between 2000 and 2002. RESULTS: Cutaneous lesions regressed within 1 to 5 months,
      with an average time of 2 to 3 months for 10 patients. In all, 4 patients
      achieved complete responses, 6 had partial responses, and 2 had no regression.
      Nasopharyngeal, pulmonary neurologic, and hepatic symptoms were also attenuated.
      Thalidomide was well tolerated. The main adverse effect was deep vein thrombosis
      in 1 patient. CONCLUSION: Thalidomide efficacy and tolerance in patients with
      cutaneous sarcoidosis merits further evaluation in a controlled trial.

PMID- 14726880
TI  - Lack of difference in the rates of hypopigmentation with 90-microsecond pulsed
      and longer dwell time carbon-dioxide laser resurfacing.
AB  - BACKGROUND: Hypopigmentation is an adverse outcome associated with carbon-dioxide
      (CO(2)) laser resurfacing. A 90-microsecond pulse produces a more favorable
      postoperative course of healing, erythema, and pain compared with a 900
      microsecond dwell time. The rate of hypopigmentation after 90-microsecond pulsed
      CO(2) resurfacing may also be reduced. To date, there have been no comprehensive
      reports on the effect of varying pulse duration on the occurrence of
      hypopigmentation. OBJECTIVE: We sought to investigate the relationship between
      pulse duration and the occurrence of hypopigmentation after CO(2) laser
      resurfacing. METHODS: We conducted a retrospective review of 447 consecutive
      patients who were treated with a 90-microsecond pulsed CO(2) laser (n = 229) or a
      continuous wave CO(2) laser with a modifiable dwell time (100-950 microseconds, n
      = 218). Follow-up ranged from 8 to 61 months (median: 27). RESULTS: A series of 4
      threshold dwell times (range: 90-950 microseconds) were used to divide patients
      into 2 treatment groups (above and below) at each threshold. The rates of
      hypopigmentation between groups were similar (range: 6.37%-9.09%) and serial chi
      square testing revealed no statistical differences between groups for each dwell
      time tested (P < 1.0). CONCLUSION: No significant relationship between pulse
      duration and the occurrence of hypopigmentation was observed.

PMID- 14726881
TI  - Interstitial heparan sulfate in granulomatous inflammatory skin diseases.
AB  - BACKGROUND: Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the
      outside of cell membranes. Under ordinary circumstances, it is not present in the
      interstitium, but under certain circumstances, mainly in the setting of
      inflammation and tissue repair, HS can be shed from the cell surface into the
      interstitium in a regulated fashion. Under these circumstances, interstitial HS
      seems to have an immunomodulatory function because of its binding of many
      cytokines. However, it is not known which cell types present at an inflammatory
      site are responsible for this shedding. OBJECTIVE: We have investigated the
      presence of interstitial HS by immunohistochemistry in various inflammatory skin
      diseases characterized by different compositions of the inflammatory infiltrate.
      RESULTS: Strong interstitial HS immunoreactivity was present only in diseases
      with a predominantly histiocytic infiltrate but not in diseases with a
      predominantly lymphocytic or neutrophilic infiltrate. CONCLUSIONS: This indicates
      that histiocytes have a direct or indirect role in the HS shedding process. In
      the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was
      spatially associated with the fibrotic ring at the periphery of the granulomas,
      but not with the center harboring the histiocytes. This suggests that histiocytes
      can stimulate fibroblasts to shed HS into the interstitium.

PMID- 14726882
TI  - The nail and hair in forensic science.
AB  - Drugs, chemicals, and biological substances accumulate and are stored in hair and
      nails where they can be detected and measured. Advantages of analyzing hair and
      nail samples also include their easy and non-invasive collection, the small
      sample size required for analysis, and their easy storage at room temperature. We
      report 3 examples of heavy metal poisoning diagnosed because of the hair or nail
      symptoms. Drugs and toxins that can be detected in hair and nails are reviewed
      and the application of hair/nail analysis in general and in forensic medicine is
      discussed.

PMID- 14726883
TI  - Domestic violence in the outpatient setting.
AB  - Domestic abuse is a serious problem that may present directly or indirectly in
      the clinical setting. The astute physician may have the opportunity to directly
      intervene in this national dilemma. We present a patient who indirectly sought
      help through the medical setting, review the physician's responsibilities, and
      offer guidelines for management.

PMID- 14726884
TI  - Temperature regulates bacterial protein production: possible role in rosacea.
AB  - Facial skin temperature is higher for patients with rosacea. Papules and pustules
      might arise because bacteria behave differently at these warmer temperatures. We
      sought to: (1) compare bacteria from facial skin of patients with rosacea with
      that of control subjects; and (2) grow these bacteria at 30 degrees C and 37
      degrees C to compare growth curves and secreted proteins. Bacteria isolated from
      pustules/skin surfaces of patients with rosacea and skin surfaces of control
      subjects were identified and cultured at 37 degrees C and 30 degrees C. Secreted
      proteins were separated by electrophoresis. We found that Staphylococcus
      epidermidis isolated from patients with rosacea was consistently beta-hemolytic,
      whereas that from control subjects were nonhemolytic. Bacteria from patients with
      rosacea grew at the same rate and to the same stationary phase whether cultured
      at 37 degrees C or 30 degrees C. Isolates from patients with rosacea secreted
      more proteins, and generally more of each protein at 37 degrees C compared with
      30 degrees C. In conclusion, bacteria isolated from patients with rosacea secrete
      different proteins and different amounts of protein at different temperatures.

PMID- 14726885
TI  - Surgical pearl: the use of towel clamps to reapproximate wound edges under
      tension.

PMID- 14726886
TI  - Surgical pearl: the single-use, surgical curette blade.

PMID- 14726887
TI  - Community-acquired methicillin-resistant Staphylococcus aureus skin infection: an
      emerging clinical problem.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus skin infections at
      an outpatient university health center were evaluated. In all, 41 cultures were
      performed in 36 of 853 patients. Of the 19 patients with S aureus infection,
      methicillin resistance occurred in 10 (53%) and generally manifested as abscesses
      or cellulitis. Therefore, methicillin resistance should be considered, even in
      the community setting, and appropriate cultures performed.

PMID- 14726888
TI  - Neutrophilic panniculitis.
AB  - Neutrophilic (lobular) panniculitis (NP) is a very rare condition that belongs to
      the group of neutrophilic dermatoses. We report the case of a patient with NP and
      review the relevant literature. NP appears as a subcutaneous nodular eruption.
      Histology shows a lobular neutrophilic infiltrate. NP must be differentiated from
      other types of panniculitis, and also from the subcutaneous septal involvement
      that may occur in some cases of Sweet's syndrome and from erythema nodosum. NP is
      significantly associated with myelodysplasia. It is highly sensitive to oral
      steroid therapy.

PMID- 14726889
TI  - Intravenous immunoglobulin prophylaxis for recurrent Stevens-Johnson syndrome.
AB  - Human intravenous immunoglobulin has been described as a treatment for patients
      with Stevens-Johnson syndrome and toxic epidermal necrolysis. We describe the
      prophylactic use of intravenous immunoglobulin to prevent Stevens-Johnson
      syndrome in a woman undergoing cardiac catheterization with a previous history of
      four episodes of Stevens-Johnson after receiving intravenous contrast dye.

PMID- 14726890
TI  - Idiopathic splinter hemorrhages.
AB  - Splinter hemorrhages are non-blanchable usually distal reddish-brown linear
      hemorrhages beneath the nails. Among a variety of etiologic factors reported,
      trauma is the most common cause. A 26-year-old Hispanic female presented with
      asymptomatic, extensive fingernail hemorrhages of two months duration. There was
      no history of physical trauma to the nails. Treatment with a topical antifungal
      medication for one month produced no improvement. The past medical history was
      noncontributory. Extensive laboratory testing revealed no underlying systemic
      disease. Three months after the initial presentation, 6 of 10 fingernails showed
      signs of resolution without treatment. We conclude that idiopathic atraumatic
      subungual splinter hemorrhages can occur in healthy individuals. Spontaneous
      resolution occurred in our patient.

PMID- 14726891
TI  - Vulvar melanoma: diffuse melanosis and metastasis to the placenta.
AB  - Mucocutaneous melanoma, including vulvar melanoma, is rare and has a worse
      prognosis and higher recurrence rate than traditional cutaneous melanoma. Diffuse
      cutaneous melanosis is another rare clinical presentation of metastatic melanoma.
      It is essential for dermatologists to be alerted to rare presentations of
      melanoma, to facilitate early detection. We present the first case to our
      knowledge of metastatic vulvar melanoma with diffuse cutaneous melanosis in a
      pregnant young woman. Despite the occurrence of placental metastasis, a healthy,
      unaffected baby was born. This case exemplifies the aggressiveness of vulvar
      melanoma. The genitalia should be included in routine total body skin
      examinations. Pregnant women with generalized melanosis may be at increased risk
      for placental metastasis of melanoma. Pregnancy does not alter the incidence or
      prognosis of melanoma; however, patients with a poor prognosis or high recurrence
      risk should be informed of potential pregnancy complications associated with
      melanoma recurrence or metastasis.

PMID- 14726892
TI  - Rapid publication for selected JAAD articles.

PMID- 14726893
TI  - Methotrexate and psoriasis in the era of new biologic agents.

PMID- 14726894
TI  - Cyclosporine-induced folliculodystrophy.
AB  - We describe a 34-year-old kidney transplant patient who developed a distinct
      cutaneous side-effect to cyclosporine manifested as an infiltrated appearance to
      the skin with abundant flesh-colored, follicular papules predominantly affecting
      the ears, nose, and surrounding areas of the face, but also the trunk and
      extremities. The clinical and histologic findings in this case closely match
      those presented in 2 previous case reports, in which immunosuppressive doses of
      cyclosporine appeared to be causative. We present a detailed report of the
      clinical and histologic findings that are unique to these 3 cases and we
      introduce a theory, based on the recent in vitro studies involving cyclosporine,
      to help explain the pathogenic events induced by cyclosporine in these patients.
      We propose the term "cyclosporine induced folliculodystrophy" or CIF as an
      appropriate name for this distinct clinicohistopathologic entity. Finally, we set
      forth 3 clinical and 4 histopathologic criteria upon which the diagnosis of CIF
      can be made.

PMID- 14726895
TI  - Infectious eccrine hidradenitis caused by Nocardia.
AB  - Neutrophilic eccrine hidradenitis is a nonspecific clinical reaction pattern
      classified as a neutrophilic dermatosis that typically occurs in the setting of
      chemotherapy for hematologic malignant disease. Neutrophilic eccrine hidradenitis
      more rarely has been reported in association with infectious agents, including
      Serratia, Enterobacter, Staphylococcus, and HIV. We describe the first case of
      infectious eccrine hidradenitis occurring in a patient with cutaneous Nocardia
      infection.

PMID- 14726896
TI  - Viral-associated trichodysplasia in patients who are immunocompromised.
AB  - Viral-associated trichodysplasia of immunosuppression is a newly described
      clinicopathologic entity found in patients who are undergoing drug-induced
      immunosuppression to prevent organ transplant rejection. Patients have numerous
      erythematous papules concentrated in the central portion of the face and variable
      degrees of hair loss, most severely affecting facial hair. Histologic findings of
      facial papules are highly distinctive and unique, and suggest that the entire
      machinery of the follicular bulb is devoted to the manufacture of inner root
      sheath-type keratin. Electron microscopy reveals intranuclear viral particles,
      but precise viral identification has not yet been achieved.

PMID- 14726897
TI  - Posttraumatic ectopic nail.

PMID- 14726898
TI  - Persistent hair loss 60 months after a single treatment with a 3-millisecond
      alexandrite (755 nm) laser.

PMID- 14726899
TI  - Topical tacrolimus treatment for cicatricial pemphigoid.

PMID- 14726900
TI  - High-dose injection of botulinum toxin to treat focal hyperhidrosis: what's wrong
      with the concept?

PMID- 14726901
TI  - Mucosal staining after using topical tacrolimus to treat erosive oral lichen
      planus.

PMID- 14726902
TI  - Evidence-based medicine and the treatment of hyperhidrosis.

PMID- 14726904
TI  - Antimicrobial treatment guidelines for acute bacterial rhinosinusitis.

PMID- 14726905
TI  - A mathematical therapeutic outcomes model for sinusitis.
AB  - The therapeutic outcomes model (TOM) provides a logical and consistent manner in
      which bacteriologic and clinical efficacy can be predicted and calculated. It not
      only allows antibiotics to be ranked in efficacy, it gives precise estimates of
      the magnitude of differences in efficacy, which is typically lacking in older
      antimicrobial guidelines. The TOM identifies the major variables that need to be
      considered in accurately estimating outcome and places those variables into the
      appropriate relationships and formulas so that outcomes will be automatically
      calculated. In the case of rhinosinusitis, the major variables are (1) likelihood
      of spontaneously resolving nonbacterial cause, (2) likelihood of nonresolving
      nonbacterial cause, (3) prevalence of subcauses (eg, different species of
      bacteria), (4) the spontaneous resolution rates of each subcause, (5) the
      antibacterial efficacy of the treatment (eg, antibiotic) against each of the
      subcauses, and (6) the compliance rate of the treatment recommended. Minor
      variables, such as prior antibiotic use, patient age, or bacterial vaccination
      status, affect the efficacy of a given agent by modifying the value of one or
      more of the major variables. The TOM is a superior mechanism for ranking and
      evaluating relative antibiotic efficacy than previous methodologies.

PMID- 14726906
TI  - Techniques of intranasal steroid use.
AB  - OBJECTIVE: The effectiveness of topical intranasal steroids (INS) sprays for the
      treatment of allergic and nonallergic rhinitis may be limited by lack of
      instruction in the optimal spray technique. To determine whether the technique
      used affects the efficacy and safety of the product, this review of evidence had
      the goal of identifying and establishing a preferred method of applying INS
      sprays. STUDY DESIGN: A MEDLINE search of pertinent literature on 7 INS and 1
      intranasal antihistamine spray preparations conducted with the use of appropriate
      search terms, yielded an initial 121 articles, 29 of which were identified as
      appropriate for review and grading for quality of evidence. RESULTS: The analysis
      provided no definitive evidence regarding how best to instruct patients to use
      INS or antihistamine spray devices. CONCLUSIONS: On the basis of a lack of clear
      evidence regarding instructions to maximize efficacy and safety of these drugs,
      the panel recommended a 7-step standard technique.

PMID- 14726907
TI  - Endoscopic management of retained airgun projectiles in the paranasal sinuses.
AB  - OBJECTIVES/HYPOTHESIS: This article presents 3 cases to illustrate the
      appropriate management of airgun injuries with retained projectiles in the
      paranasal sinuses. The indications, techniques, and potential complications of
      removal of these foreign bodies from the paranasal sinuses are discussed. STUDY
      DESIGN: We conducted a case series consisting of 3 patients and a review of the
      literature. METHODS: Three consecutive patients who sustained airgun injuries to
      the face with retained bullets in the paranasal sinuses are presented.
      Projectiles were present in the maxillary, ethmoid, and sphenoid sinuses. The
      literature pertaining to this subject is reviewed. RESULTS: All retained
      projectiles were removed endoscopically without complications. Stereotactic
      guidance was used in 2 cases. CONCLUSIONS: Airgun injuries to the paranasal
      sinuses are relatively uncommon. Projectiles can safely be removed using
      endoscopic techniques in selected cases. When possible, foreign bodies in the
      paranasal sinuses should be removed to prevent long-term sequelae.

PMID- 14726908
TI  - Cost-utility analysis for endoscopic sinus surgery.
AB  - OBJECTIVE: To undertake cost-utility analysis for endoscopic sinus surgery (ESS)
      in order to analyze the cost-effectiveness of different chronic sinusitis
      severity groups. METHODS: One hundred ninety-two patients with chronic sinusitis
      were evaluated with a Chronic Sinusitis Survey (CSS) before and 1-year after ESS.
      Direct health care cost data during the first year after operation were
      retrieved. The utility gain is defined as change in the CSS total score. The cost
      utility ratio was defined as cost per utility gain. Patients are stratified by
      disease severity using the Harvard Staging System. RESULTS: The average total
      direct cost attributable to ESS is 40,829 NT dollars in the first postoperative
      year and the average cost-utility ratio is 2194.42 NT dollars. The high cost
      utility ratio of 3246.45 NT dollars for pansinusitis cases is due to the higher
      cost and limited utility gain. CONCLUSIONS: Treating mild and moderate chronic
      sinusitis are most cost-effective because of their favorable utility gain and
      relatively reasonable cost. However, there is no proportional linear relationship
      between disease severity and cost-utility ratio.

PMID- 14726909
TI  - Endoscopic dacryocystorhinostomy: modified technique.
AB  - BACKGROUND: Dacryocystorhinostomy (DCR) is a surgical technique that has been
      increasingly used by otolaryngologists in recent years due to the improved
      endonasal approach with endoscopes. Although it was first described in 1893 by
      Caldwell, it has been performed by ophthalmologists. OBJECTIVES: Even though
      permeability results are similar in long-term follow-up, we present some
      modifications that in our opinion contribute to the improvement of the results
      and the simplification of the surgical technique: mucosal flap design that helps
      to improve the postoperative mucosal recovery, careful dissection of the bony
      suture between the frontal process of the maxillary bone and the lacrimal bone,
      and osteotomy using a Smith-Kerrison forceps. STUDY DESIGN AND SETTING: Two
      groups are compared. In the first group (96 DCRs), patients underwent chisel
      osteotomies without a mucosal flap of the lacrimal duct, and in the second group
      (40 DCRs), the modified technique was applied. RESULTS: Final permeability
      results are similar (92.7% versus 87.5%). No major complications were found, and
      the most common minor complication was postoperative eyelid hematoma in cases
      where orbital fat was exposed (5 cases versus 7 cases). CONCLUSIONS: There are no
      differences in final results, but the modified technique is easier to perform,
      improves postoperative mucosal recovery, is more functional and less aggressive,
      and improves the cost-benefit ratio.

PMID- 14726911
TI  - Acoustic pharyngometry patterns of snoring and obstructive sleep apnea patients.
AB  - OBJECTIVE: Anatomic narrowing of the pharyngeal airway increases the relative
      negative pressure generated during inspiration, thus affecting the dynamic
      behavior of the upper airway. The aim of this work was to measure pharyngeal area
      in snoring patients with and without obstructive sleep apnea (OSA), as
      categorized by polysomnography and by acoustic pharyngometry, and to analyze the
      different curve patterns obtained from patients of both groups. METHODS: We
      examined 50 snorers who were divided into 2 groups matched for age, gender, and
      body mass index. RESULTS: Mean Apnea Index (AI) in nonapneic snorers (group 1)
      was 4, and mean pharyngeal area was 2.41 cm(2). In snoring patients with OSA
      (group 2), mean AI was 25.9 with a mean pharyngeal area of 1.589 cm(2) (P <
      0.001). In both groups, the dependent variable (AI) can be predicted from a
      linear relation with the independent variable (pharyngeal area) with normality
      and constant variance tests passed. In group 1, the resulting curve can be 1 of 2
      types depending on the relative area of the pharyngeal segment to the
      velopharyngeal area. In group 2, the curve pattern can be categorized into 3
      patterns depending on the possible pathology of pharyngeal obstruction.
      CONCLUSION: The acoustic reflection technique is reproducible, noninvasive, and
      free from potential side effects. The good correlation between AI and pharyngeal
      area adds to the potential of acoustic pharyngometry. Careful study of the
      pharyngeal cross-sectional area and curve topography may give a good idea about
      the site of upper airway obstruction.

PMID- 14726910
TI  - Injection snoreplasty: investigation of alternative sclerotherapy agents.
AB  - OBJECTIVE: Palatal sclerotherapy with sodium tetradecyl sulfate ("injection
      snoreplasty") was recently introduced as a safe and effective treatment for
      primary snoring. However, multiple other sclerotherapy agents also have excellent
      safety records and documented efficacy in the head and neck. Widely available and
      inexpensive agents were evaluated as potential palatal sclerosing agents for the
      treatment of snoring. STUDY DESIGN AND SETTING: A described canine palatal
      flutter model was used to evaluate the palatal stiffening efficacy of ethanol,
      doxycycline, and hypertonic saline in comparison to 3% sodium tetradecyl sulfate
      (STS) and a negative control (normal saline). Based on the animal study results,
      a human pilot study with ethanol was performed with subjective and objective
      data. RESULTS: Ethanol was found to be equally effective as 3% STS in the canine
      model. Doxycycline was effective but less so, and hypertonic saline was
      comparatively ineffective. Palatal injection in human patients with 50% ethanol
      was found to produce equivalent subjective and objective snoring efficacy and
      equivalent pain and recovery time compared with 3% STS. However, there was a
      higher rate of transient palatal fistula with ethanol. CONCLUSIONS AND
      SIGNIFICANCE: Injection snoreplasty with 50% ethanol is equally efficacious
      compared with 3% STS. There could be a higher fistula rate with the use of
      ethanol, although this complication has been self-limited and transient in every
      case.

PMID- 14726912
TI  - Radiofrequency soft palate procedure in snoring: influence of energy delivered.
AB  - OBJECTIVE: We conducted a retrospective study to evaluate the influence of amount
      of energy delivered during radiofrequency procedure for soft palate reduction in
      snoring, to improve the cure rate. METHODS: Consecutive patients with chronic
      disruptive snoring presenting to our department were successively treated in an
      outpatient procedure. A visual analog scale was used to assess the severity of
      snoring by the bed partner and the pain by the patient, before treatment and
      after each treatment session. The soft palate was divided into 3 treatment sites:
      middle, lateral right, and lateral left. Any mucosal injury of the soft palate
      was classified as a complication. RESULTS: Forty-3 patients were classified into
      2 groups according to energy assignment. The total amount of energy delivered was
      1250 J in group 1 (n = 15) and 1500 J in group 2 (n = 28). Energy was
      predominantly distributed in the middle of the soft palate in group 1 (550 J) and
      group 2 (800 J). After each treatment session, the 1500-J delivery of
      radiofrequency energy (total per session) led to a better snoring grading
      reduction in comparison with the 1250-J delivery with a significant difference
      after 2 treatment sessions (P < 0.05). The mean pain score and the incidence rate
      of complications per treatment were not statistically different in comparing both
      groups. CONCLUSION: Better snoring scores can be expected by increasing
      radiofrequency energy applied to the soft palate. Further randomized long-term
      investigations are required to confirm that the cure rate can be improved when
      increasing energy with a suitable distribution and good clinical tolerance.

PMID- 14726913
TI  - The role of the Genial Bone Advancement Trephine system in conjunction with
      uvulopalatopharyngoplasty in the multilevel management of obstructive sleep
      apnea.
AB  - OBJECTIVES: The successful surgical management of obstructive sleep apnea (OSA)
      requires surgical procedures that address both retropalatal and retrolingual
      airway obstruction. The Genial Bone Advancement Trephine (GBAT) system is a new,
      1-step system that allows for isolation and advancement of the genioglossus
      muscle via a guided trephine system. The purpose of this project was to describe
      our experience using the GBAT system to perform genioglossus advancement (GGA) in
      conjunction with uvulopalatopharyngoplasty (UPPP) in the surgical management of
      OSA. STUDY DESIGN: Retrospective analysis of 35 consecutive patients undergoing
      GGA using the GBAT system in conjunction with UPPP for the management of OSA
      during a 3-year period (1999 to 2002). RESULTS: Twenty-four patients had complete
      preoperative and postoperative polysomnographic data. A 70% reduction in the
      Respiratory Disturbance Index (RDI) and Apnea Index (AI) in the preoperative
      versus postoperative PSG (RDI, 52.9 +/- 17.1 versus 15.9 +/- 7.5; AI, 20.1 +/-
      6.7 versus 6.1 +/- 4.5; P < or = 0.0001). The lowest oxygen desaturation
      increased from 80% to 88% (P = 0.0002), and the posterior airway increased from
      7.9 to 12.6 mm (P < 0.0001). With a surgical cure defined as a greater than 50%
      reduction in the RDI and a final postoperative RDI of less than 20 events per
      hour, the true surgical cure rate was 67% (16 of 24 patients). CONCLUSIONS: The
      GBAT system performed in conjunction with UPPP can produce significant reductions
      in RDI and AI while improving the oxygen desaturation and enlarging the posterior
      airway space. The effective cure rates using the GBAT system are in agreement
      with previous reports in the literature using various GGA techniques. The GBAT
      may have some advantages in terms of simplicity and safety.

PMID- 14726914
TI  - The risk of aspiration of pureed food as determined by flexible endoscopic
      evaluation of swallowing with sensory testing.
AB  - OBJECTIVE: This study evaluates the risk of aspiration of pureed foods in
      patients with dysphagia with increasing sensory deficits of the hypopharynx with
      intact versus impaired pharyngeal muscular tone (pharyngeal squeeze). STUDY
      DESIGN: Two hundred four dysphagic patients underwent flexible endoscopic
      evaluation of swallowing with sensory testing and were prospectively divided into
      3 groups, with normal, moderate, and severe sensory deficits. Each group was
      divided into those with normal and those with impaired pharyngeal squeeze.
      Subjects were given pureed food boluses and were evaluated for aspiration.
      RESULTS: There was a significant difference in the incidence of aspiration of
      pureed foods for normal and moderate sensory loss when comparing normal and
      impaired pharyngeal squeeze (P < 0.001, Fisher exact test). There was no
      significant difference in the severe sensory loss group. In both the normal and
      impaired pharyngeal squeeze groups, there was no significant difference in
      aspiration as the sensory deficit increases. CONCLUSIONS: Patients with impaired
      pharyngeal squeeze at different levels of sensory deficits are at significantly
      greater risk for aspiration of pureed foods compared with those with normal
      squeeze. However, as sensory deficits increased, the patients did not show a
      significant increase in aspiration. The aspiration of pureed foods may depend
      more on muscle tone of the hypopharynx than on sensation. Dysphagic patients who
      are given a pureed diet to prevent aspiration may still be at risk for
      aspiration. This may be easily predicted by the use of flexible endoscopic
      evaluation of swallowing with sensory testing in conjunction with evaluation of
      pharyngeal muscle tone.

PMID- 14726915
TI  - Carbon dioxide laser salvage surgery after radiotherapy failure in T1 and T2
      glottic carcinoma.
AB  - OBJECTIVES: Recurrent glottic carcinoma after radiotherapy (RT) may be managed by
      open neck or endoscopic surgery. The impact of endoscopic treatment with CO(2)
      laser for recurrent glottic carcinoma after RT is reported. METHODS: We present
      the oncologic and vocal outcomes of a retrospective study based on a series of 16
      patients with rT1 and rT2 glottic carcinoma who were endoscopically managed
      between February 1995 and December 1999 after RT failure. All patients were males
      with a mean age of 68.7 years (range, 50 to 87 years). Before RT, the lesions had
      been staged as T1 N0 in 11 patients and T2 N0 in 5, and after RT as rT1 N0 in 12
      and rT2 N0 in 4. According to the European Laryngological Society classification,
      a total of 9 transmuscular, 3 total, and 4 extended cordectomies were performed.
      Mean follow-up was 45 months (range, 9 to 79 months). RESULTS: Endoscopic salvage
      surgery was successful in 14 patients. One of them developed a second recurrence
      and was definitively cured with an additional endoscopic procedure. Two of the 16
      patients had recurrent disease after salvage laser surgery and died due to
      progression of disease. Ultimate local control with laser alone at 3 years was
      87.1%, according to the Kaplan-Meier method. Laryngeal preservation was obtained
      in all survivors after endoscopic rescue surgery. Voice analysis showed a clear
      correlation between the amount of vocal cord tissue resected and decrease of the
      vocal outcome. CONCLUSIONS: The present series indicates that selected
      recurrences after primary RT for T1 and T2 glottic carcinoma are eligible for
      endoscopic salvage surgery with oncologic results comparable to those with open
      neck procedures but with a lower complication rate and a favorable functional
      outcome.

PMID- 14726916
TI  - Localization and level of expression of beta-catenin in human laryngeal squamous
      cell carcinoma.
AB  - OBJECTIVE: We studied the participation of beta-catenin in the histologic
      differentiation of laryngeal squamous cell carcinomas. STUDY DESIGN AND SETTING:
      At the National Institute of Respiratory Diseases, a tertiary referral center,
      localization and level of expression of beta-catenin were compared between normal
      epithelium (15 cases) and primary tumors in different degrees of differentiation
      (38 cases), using an immunohistochemical procedure. RESULTS: Cell membrane
      staining of beta-catenin was observed in normal epithelium and in well and
      moderately differentiated carcinomas. Cytoplasmic redistribution was observed in
      poorly differentiated carcinomas. Loss of beta-catenin correlated with tumor
      dedifferentiation. CONCLUSION: Reduction of cell membrane beta-catenin expression
      correlated with tumor dedifferentiation. SIGNIFICANCE: Loss of beta-catenin may
      lead to diminishing the strength of the intercellular adhesion system, thereby
      promoting the invasive phenotype of the squamous cell carcinoma of the larynx.

PMID- 14726917
TI  - CD40 monoclonal antibody activation of antigen-presenting cells improves
      therapeutic efficacy of tumor-specific T cells.
AB  - OBJECTIVE: The goal of this study was to determine whether CD40 ligation of
      antigen presenting cells (APCs) enhances the anti-tumor effector function of
      tumor draining lymph node (TDLN) T lymphocytes in an adoptive immunotherapy
      model. STUDY DESIGN: MCA 205 TDLNs were culture activated both in the presence
      and absence of a stimulatory anti-CD40 monoclonal antibody (mAb) and effector
      cell phenotype, cytokine secretion in vitro and therapeutic efficacy in vivo were
      compared. RESULTS: Anti-CD40 mAb induced upregulation of APC cell surface
      activation markers that promoted generation of T cells that demonstrated an
      increase in tumor-specific IFN-gamma secretion and a statistically significant
      reduction in the number of pulmonary tumors (p< 0.01) after adoptive transfer.
      CONCLUSION: CD40 ligation of APCs in vitro results in the generation of T cells
      with enhanced effector function against established pulmonary tumors in vivo.
      SIGNIFICANCE: These findings have direct implications in the development of
      effective T cell-based immunotherapy of malignant conditions in human beings.

PMID- 14726918
TI  - The fate of the tumor remnant after less-than-complete acoustic neuroma
      resection.
AB  - OBJECTIVES: We sought to determine the recurrence rate after near-total and
      subtotal resection of acoustic neuroma. STUDY DESIGN, SETTING, AND PATIENTS: We
      conducted a retrospective chart review of a total of 79 patients: 50 with near
      total resections (remnant < or =25 mm(2) and < or =2 mm thick) and 29 with
      subtotal resections (any larger remnant). Surgical approach included 5 middle
      fossa, 17 retrosigmoid, and 57 translabyrinthine. MAIN OUTCOME MEASURES:
      Recurrence was defined as documented tumor growth by serial imaging or the
      recommendation for further treatment after a single scan. No recurrence was
      defined as no visible tumor on imaging for a minimum follow-up time of 3 years or
      tumor remnants that remained unchanged on serial scans (mean, 5-year follow-up).
      RESULTS: Fifty-two patients were included in the study group. Recurrences were
      seen in 1 (3%) of 33 patients who had a near-total resection compared with 6
      (32%) of 19 patients who had a subtotal resection. After adjustment for follow-up
      time and large tumor size, the odds ratio for recurrence was 12 times larger for
      subtotal than for near-total resections (P = 0.033). All recurrences were seen
      following the translabyrinthine approach in the mid-cerebellopontine angle. None
      were encountered in the internal auditory canal. The mean time interval from
      surgery to the detection of a recurrence was 3 years (range, 1 to 5 years).
      CONCLUSIONS: The recurrence rate when performing a near-total resection is low
      but is substantially higher with a subtotal resection. Recurrences can be
      detected within the first 5 postoperative years. We recommend near-total
      resection in any patient if needed to preserve neural integrity. Subtotal
      resection is best avoided whenever possible; however, adjunctive treatment with
      stereotactic radiotherapy may be considered.

PMID- 14726919
TI  - Cellular changes of Reissner's membrane in Meniere's disease: human temporal bone
      study.
AB  - OBJECTIVE: To study the cellular characteristics of Reissner's membrane (RM) in
      temporal bones (TBs) from patients with endolymphatic hydrops with symptoms of
      Meniere's disease (EH/+MD) and TBs with endolymphatic hydrops without symptoms of
      Meniere's disease (EH/-MD) in an effort to understand the role of endolymphatic
      hydrops in MD symptoms. STUDY DESIGN: Comparative study of human TB
      histopathology. METHODS AND MATERIALS: Epithelial and mesothelial cellularity of
      RM from control TBs, TBs from patients with EH/+MD, and TBs from patients with
      EH/-MD were compared. The cellularity of epithelial and mesothelial cell nuclei
      (defined as number of cells/100 microm width of RM) were counted along the width
      of RM. The width of RM was measured from the vestibular crest of the spiral
      ligament to the limbus spiralis. RESULTS: The cellular densities of epithelial
      cells in the basal and middle turns of RM were significantly higher in the EH/+MD
      and EH/-MD groups compared with "controls." There was no difference in epithelial
      cellularity between EH/+MD and EH/-MD. There was a decrease in the number of
      mesothelial cells of RM in the basal turn in EH/+MD and EH/-MD groups
      (statistically significant only in EH/+MD group) when compared with controls. The
      number of mesothelial cells of RM in the middle turn in EH/+MD and EH/-MD groups
      were significantly decreased compared with normals. DISCUSSION: Similar findings
      in cellularity of RM in temporal bones with EH/+MD and EH/-MD suggest that
      pathophysiologic mechanisms other than hydrops may be responsible for symptoms in
      Meniere's disease.

PMID- 14726920
TI  - Total ossiculoplasty with footplate removal.
AB  - OBJECTIVE: We reviewed the results and management of cases in which total
      ossiculoplasty requires footplate removal. STUDY DESIGN AND SETTING: We conducted
      a retrospective review of 10 patients who underwent total ossiculoplasty with
      footplate removal between 1999 and 2002. These 10 patients represented 5.4% of
      those undergoing stapedectomy (n = 91) and ossiculoplasty (n = 93) during these
      years at a tertiary otologic referral center. RESULTS: A total of 10 patients
      were evaluated, with a mean 17-month follow-up. Closure of air-bone gap (ABG) to
      within 20 dB was achieved in 6 of 10 patients (60%). Mean postoperative ABG was
      21.7 dB (500 to 4000 Hz) with an average 4-frequency pure tone improvement of
      20.7 dB. Operative findings included extensive tympanosclerosis, partial
      obstruction of oval window by facial nerve, and changes from prior surgery. There
      were no patients with postoperative sensorineural hearing loss. CONCLUSIONS: The
      need to open the footplate in cases of total ossiculoplasty is uncommon. This may
      be accomplished with good improvement in hearing with minimal risk.

PMID- 14726922
TI  - Safety review of benzalkonium chloride used as a preservative in intranasal
      solutions: an overview of conflicting data and opinions.
AB  - BACKGROUND: For most multiuse aqueous nasal, ophthalmic, and otic products,
      benzalkonium chloride (BKC) is the preservative of choice. The American College
      of Toxicology has concluded that BKC can be safely used as an antimicrobial agent
      at concentrations up to 0.1%. BKC has been in clinical use since 1935 and is
      contained in a wide variety of prescription and over-the-counter products.
      However, over the past several years there have been conflicting reports of
      damage to human nasal epithelia and/or exacerbation of rhinitis medicamentosa
      associated with intranasal products containing BKC. OBJECTIVE: We sought to
      review the published literature and determine whether there is sufficient,
      clinically significant data that would confirm that intranasal products
      containing BKC are likely to damage human nasal epithelia or exacerbate rhinitis
      medicamentosa. METHODS: A literature search was conducted for in vivo and in
      vitro studies that evaluated the effects of BKC on human nasal epithelia.
      RESULTS: A total of 18 studies (14 in vivo, 4 in vitro) were identified that
      evaluated short- and long-term exposure of concentrations of BKC in
      concentrations ranging from 0.00045% to 0.1%. Eight studies, including a 6-month
      and 1-year long-term treatment study, demonstrated no toxic effects associated
      with BKC, indicating that BKC was neither harmful to nasal tissue nor prone to
      exacerbate rhinitis medicamentosa. Furthermore, of the 10 studies that concluded
      that BKC resulted in degenerative changes in human nasal epithelia (eg, ciliary
      beat frequency, ciliary morphology, mucociliary clearance, epithelial thinning
      and/or destruction) or that BKC exacerbates rhinitis medicamentosa, only 2 (it
      was 2 according to the Results section) of these studies were supported by
      statistically significant differences between BKC and placebo or active control
      groups were compared. It is important to note that in both of these studies, the
      protocol incorporated the use or oxymetazoline in some or all of the subjects.
      Oxymetazoline is associated with rhinitis medicamentosa. CONCLUSION: Intranasal
      products containing the preservative BKC appear to be safe and well tolerated for
      both long- and short-term clinical use.

PMID- 14726921
TI  - Nasopharyngeal granulomatous inflammation and tuberculosis complicating
      undifferentiated carcinoma.
AB  - OBJECTIVE: Four cases of nasopharyngeal granulomatous inflammation after
      radiotherapy for undifferentiated carcinoma were analyzed for tuberculosis, and
      the histologic features were compared. STUDY DESIGN AND SETTING: We conducted a
      retrospective study with analysis of tuberculosis by Ziehl Neelsen staining and
      polymerase chain reaction analysis for Mycobacterium tuberculosis DNA on
      histologic materials. RESULTS: Three patients had previous nasopharyngeal
      undifferentiated carcinoma, one had previous metastatic undifferentiated
      carcinoma to cervical lymph nodes, and all patients received similar radiotherapy
      regimen. The light microscopic features were similar with epithelioid histiocytes
      and granulomas with Langhan's giant cells. In 3 cases, acid-fast bacilli were
      identified by Ziehl Neelsen stain, and 1 was negative. The results of 2 cases
      were confirmed by polymerase chain reaction analysis for Myocbacterium
      tuberculosis DNA. CONCLUSION: Granulomatous reaction after radiotherapy of
      nasopharyngeal undifferentiated carcinoma can be caused by tuberculosis.
      SIGNIFICANCE: Diligent search for organisms in postirradiation granulomatous
      inflammation is warranted to avoid missing an occult tuberculosis infection.

PMID- 14726923
TI  - Inverting papilloma of the base of tongue with malignant transformation.

PMID- 14726924
TI  - Deglutition syncope.

PMID- 14726925
TI  - Microcystic adnexal carcinoma of the external ear canal.

PMID- 14726926
TI  - Rheumatoid nodules of the antihelix: a case report.

PMID- 14726927
TI  - TILLING--a high-throughput harvest for functional genomics.

PMID- 14726929
TI  - Parents of multiples and decision-making.

PMID- 14726930
TI  - Views of bereaved multiple-birth parents on life support decisions, the dying
      process, and discussions surrounding death.
AB  - OBJECTIVE: This study assessed the experiences of bereaved parents of multiples
      with resuscitation and life-support discussions, the death process, and
      conversations with health-care professionals about death. STUDY DESIGN: In all,
      71 bereaved parents of multiples recruited from Internet support groups completed
      a narrative e-mail survey assessing many facets of bereavement. Numeric data were
      analyzed using simple quantitative analysis, with a grounded theory approach used
      for qualitative data. RESULTS: Most decisions were collaborative, with occasional
      directive comments. Some decisions were made during crises. Occasionally, parents
      initiated life-support discussions. Multidisciplinary meetings occurred with 30%,
      but were desired by more parents. A total of 18% of parents encountered criticism
      of choices. Most parents attended resuscitation, and found meaning in holding
      their dying children. Many desire privacy, availability of symptom management,
      and family or clergy involvement. Photographs of multiples together are valued.
      Parents offered many suggestions for compassionate death notification, which most
      felt should occur in person if parents are not present for the death. Respondents
      valued clear, prompt discussion of the cause of death, and clinician availability
      for later review of clinical events or decisions. CONCLUSIONS: Multiple-birth
      parents' choices resemble those of singleton parents at the end of an infant's
      life.

PMID- 14726931
TI  - Effect of administering recombinant erythropoietin to women with postpartum
      anemia: a meta-analysis.
AB  - OBJECTIVES: Recombinant erythropoietin (rEpo) has been administered to women with
      postpartum anemia in an attempt to accelerate their increase in hemoglobin
      concentration and reduce postpartum transfusions. However, it is not clear
      whether such an approach can be supported by evidence and should be generally
      recommended. STUDY DESIGN AND METHODS: Medical and scientific literature from
      January 1990 to December 2002 was searched and studies that reported the
      administration of rEpo to women with postpartum anemia were evaluated. RESULTS:
      Eight evaluated studies reported an aggregate of 480 women; 300 rEpo recipients
      and 180 controls. Significant diversity in design was observed in rEpo dose,
      route of rEpo administration, iron supplementation, and baseline hemoglobin. No
      significant safety concerns were reported. In all five studies where it was
      reported, 4 to 7 days after beginning treatment, greater increases in hemoglobin
      concentration were observed among the rEpo recipients than among the controls.
      However, heterogeneity of results (Q-test statistic, p<0.01) indicated that it
      was not appropriate to apply summary statistics. The effect of rEpo on postpartum
      transfusion rate was not measurable by summary statistics because of the limited
      number of transfusions given (no transfusions among the 300 rEpo recipients vs
      two transfusions among the 180 controls). CONCLUSION: Administration of rEpo to
      women with postpartum anemia appears to be safe, and is associated with a trend
      toward a faster increase in hemoglobin concentration. However, its efficacy in
      terms of diminishing postpartum transfusions is unproven.

PMID- 14726932
TI  - Postnatal lactate as an early predictor of short-term outcome after intrapartum
      asphyxia.
AB  - OBJECTIVES: To compare the predictive value of pH, base deficit and lactate for
      the occurrence of moderate-to-severe hypoxic ischaemic encephalopathy (HIE) and
      systemic complications of asphyxia in term infants with intrapartum asphyxia.
      STUDY DESIGN: We retrospectively reviewed the records of 61 full-term neonates (>
      or =37 weeks gestation) suspected of having suffered from a significant degree of
      intrapartum asphyxia from a period of January 1997 to December 2001. The clinical
      signs of HIE, if any, were categorized using Sarnat and Sarnat classification as
      mild (stage 1), moderate (stage 2) or severe (stage 3). Base deficit, pH and
      plasma lactate levels were measured from indwelling arterial catheters within 1
      hour after birth and thereafter alongwith every blood gas measurement. The
      results were correlated with the subsequent presence or absence of moderate-to
      severe HIE by computing receiver operating characteristic curves. RESULTS: The
      initial lactate levels were significantly higher (p=0.001) in neonates with
      moderate-to-severe HIE (mean+/-SD=11.09+/-4.6) as compared to those with mild or
      no HIE (mean+/-SD=7.1+/-4.7). Also, the lactate levels took longer to normalize
      in these babies. A plasma lactate concentration >7.5+/-mmol/l was associated with
      moderate-or-severe HIE with a sensitivity of 94% and specificity of 67%. The
      sensitivity and negative predictive value of lactate was greater than that of the
      pH or base deficit. CONCLUSIONS: The highest recorded lactate level in the first
      hour of life and serial measurements of lactate are important predictors of
      moderate-to-severe HIE.

PMID- 14726933
TI  - Decreased bone ultrasound velocity in large-for-gestational-age infants.
AB  - BACKGROUND: Bone speed of sound is a measure of bone breakability. There are few
      reports on bone mineral content in large for gestational age infants; most of
      them in infants of diabetic mothers. There are no data on bone speed of sound in
      large for gestational age infants of nondiabetic mothers. OBJECTIVE: To test the
      hypothesis that large for gestational age infants of nondiabetic mothers have
      lower bone speed of sound than appropriate for gestational age infants.
      DESIGN/METHODS: Bone speed of sound was measured within the first 96 hours of
      life at the right tibial midshaft in 25 singleton large for gestational age
      infants of non diabetic mothers and compared to appropriate for gestational age
      controls. RESULTS: Bone speed of sound measured in large for gestational age
      infants of nondiabetic mothers was lower than in controls. CONCLUSIONS: Large for
      gestational age infants of nondiabetic mothers have lower bone speed of sound
      than controls.

PMID- 14726934
TI  - Effect of beginning recombinant erythropoietin treatment within the first week of
      life, among very-low-birth-weight neonates, on "early" and "late" erythrocyte
      transfusions: a meta-analysis.
AB  - OBJECTIVES: Erythrocyte transfusions to neonates can be categorized as "early" if
      given during the first 3 weeks of life and "late" if given thereafter. We used a
      meta-analysis to determine whether recombinant erythropoietin (rEpo)
      administration to very-low-birth-weight (VLBW, <1500 g) neonates, beginning in
      the first week of life, reduces either "early" or "late" transfusions. STUDY
      DESIGN AND METHODS: Studies that used a randomized, placebo-controlled, double
      masked design were deemed acceptable. We identified 12 acceptable, relevant,
      clinical trials. Additional data not provided in the publications were obtained
      from two of the authors. RESULTS: The acceptable studies involved an aggregate of
      561 rEpo and 529 placebo recipients. If rEpo was begun in the first week of life,
      the summary odds ratio (OR) for receiving any transfusion ("early" or "late") was
      0.52, 95% confidence interval (CI): 0.34 to 0.79 (p=0.001). The OR for receiving
      an "early" transfusion was 0.54 (95% CI: 0.25 to 1.15; p=0.055), and the OR for
      receiving a "late" transfusion was 0.56 (95% CI: 0.37 to 0.83; p=0.036).
      Heterogeneity among studies was too great to estimate the effect of rEpo on the
      number of transfusions received or the volume of blood transfused (p<0.001 for
      the Q-test statistic). Subgroup analysis suggested that when rEpo is begun in the
      first week of life, neonates 1000 to 1500 g and >29 weeks are more likely to
      completely avoid transfusion than are extremely low-birth-weight (ELBW, <1000 g)
      neonates. No dose-response relationship was apparent between rEpo dose or iron
      dose and transfusion. No difference was apparent depending on whether the rEpo
      was given subcutaneously vs intravenously. CONCLUSION: If rEpo is begun in the
      first week of life, a moderate reduction can be expected (p=0.001) in the
      proportion of VLBW neonates transfused. Reduction is less significant in "early"
      transfusion (p=0.055) than in "late" transfusion (p=0.036). Such treatment is not
      likely to eliminate transfusions among ELBW neonates completely.

PMID- 14726935
TI  - Association of glutathione-S-transferase-P1 (GST-P1) polymorphisms with
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: Reactive oxygen species (ROS) contribute to oxidative lung injury. The
      glutathione-S-transferases (GST) family and microsomal epoxide hydrolase (mEPHx)
      enzymes detoxify ROS, and genetic polymorphisms alter this detoxification. We
      hypothesized that polymorphisms encoding for less efficient enzymes were
      associated with bronchopulmonary dysphasia (BPD). STUDY DESIGN: We determined
      allelic distribution of these polymorphisms in a pilot study of 35 BPD cases and
      98 controls. chi2 and regression analysis were performed. RESULTS: GST P1
      val105ile distribution differed between the groups, with the more efficient
      val/val allele predominantly in controls (p< or =0.05). When controlling for race
      and sex, BPD cases were less likely to be homozygotes for the val/val isoform (OR
      0.21, CI: 0.045-0.95, p=0.04) and more likely to possess the less efficient ile
      isoform (OR 4.5, CI: 1.0-20.7, p=0.05). CONCLUSIONS: This pilot study suggests
      that BPD is associated with the presence of the GST-P1 105ile allele. Future
      prospective studies are warranted.

PMID- 14726936
TI  - Controversy surrounding the use of home oxygen for premature infants with
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: To determine the criteria used in the current practice of neonatology
      for the initiation of home oxygen therapy in premature infants with
      bronchopulmonary dysplasia and to compare these criteria with the available
      literature regarding the use of home oxygen therapy. STUDY DESIGN: Participants
      in the December 2000 meeting of the Vermont Oxford Network were surveyed
      regarding their current use of home oxygen therapy for infants with
      bronchopulmonary dysplasia. RESULTS: Surveys were returned by 181 out of 297
      participants. Pulse oximetry saturation (SpO2) thresholds for the initiation of
      home oxygen therapy varied widely from <84% to <98%. The most common threshold
      was <90% chosen by only 43% of the respondents. Additionally, 22% of the
      respondents did not initiate therapy until the oxygen saturation in room air was
      below 88%. Once on oxygen therapy, the target SpO2 also varied widely from >84%
      to >98%, with only 27% of respondents aiming for an SpO2 of >94%. CONCLUSIONS:
      There is a clear lack of consensus among neonatologists regarding the initiation
      of home oxygen therapy for bronchopulmonary dysplasia. Furthermore, the criteria
      used for home oxygen therapy varies widely with the majority of neonatologists
      surveyed using oxygen saturation levels not supported by the literature. We
      speculate that a significant underutilization of home oxygen therapy exists for
      infants with bronchopulmonary dysplasia.

PMID- 14726937
TI  - Dystrophic epidermolysis bullosa.

PMID- 14726938
TI  - Umbilical cord stricture in a 21-week fetus.

PMID- 14726939
TI  - Imaging casebook. Asplenia syndrome with congenital microgastria and malrotation.

PMID- 14726940
TI  - Meconium periorchitis.

PMID- 14726941
TI  - Angiotensin II receptor antagonist in pregnancy.

PMID- 14726942
TI  - A pilot study using scripted ventilation conditions to identify key factors
      affecting indoor pollutant concentration and air exchange rate in a residence.
AB  - A pilot study was conducted using an occupied, single-family test house in
      Columbus, OH, to determine whether a script-based protocol could be used to
      obtain data useful in identifying the key factors affecting air-exchange rate
      (AER) and the relationship between indoor and outdoor concentrations of selected
      traffic-related air pollutants. The test script called for hourly changes to
      elements of the test house considered likely to influence air flow and AER,
      including the position (open or closed) of each window and door and the operation
      (on/off) of the furnace, air conditioner, and ceiling fans. The script was
      implemented over a 3-day period (January 30-February 1, 2002) during which
      technicians collected hourly-average data for AER, indoor, and outdoor air
      concentrations for six pollutants (benzene, formaldehyde (HCHO), polycyclic
      aromatic hydrocarbons (PAH), carbon monoxide (CO), nitric oxide (NO), and
      nitrogen oxides (NO(x))), and selected meteorological variables. Consistent with
      expectations, AER tended to increase with the number of open exterior windows and
      doors. The 39 AER values measured during the study when all exterior doors and
      windows were closed varied from 0.36 to 2.29 h(-1) with a geometric mean (GM) of
      0.77 h(-1) and a geometric standard deviation (GSD) of 1.435. The 27 AER values
      measured when at least one exterior door or window was opened varied from 0.50 to
      15.8 h(-1) with a GM of 1.98 h(-1) and a GSD of 1.902. AER was also affected by
      temperature and wind speed, most noticeably when exterior windows and doors were
      closed. Results of a series of stepwise linear regression analyses suggest that
      (1) outdoor pollutant concentration and (2) indoor pollutant concentration during
      the preceding hour were the "variables of choice" for predicting indoor pollutant
      concentration in the test house under the conditions of this study. Depending on
      the pollutant and ventilation conditions, one or more of the following variables
      produced a small, but significant increase in the explained variance (R(2)-value)
      of the regression equations: AER, number and location of apertures, wind speed,
      air-conditioning operation, indoor temperature, outdoor temperature, and relative
      humidity. The indoor concentrations of CO, PAH, NO, and NO(x) were highly
      correlated with the corresponding outdoor concentrations. The indoor benzene
      concentrations showed only moderate correlation with outdoor benzene levels,
      possibly due to a weak indoor source. Indoor formaldehyde concentrations always
      exceeded outdoor levels, and the correlation between indoor and outdoor
      concentrations was not statistically significant, indicating the presence of a
      strong indoor source.

PMID- 14726943
TI  - Developing meaningful cohorts for human exposure models.
AB  - This paper summarizes numerous statistical analyses focused on the US
      Environmental Protection Agency's Consolidated Human Activity Database (CHAD),
      used by many exposure modelers as the basis for data on what people do and where
      they spend their time. In doing so, modelers tend to divide the total population
      being analyzed into "cohorts", to reduce extraneous interindividual variability
      by focusing on people with common characteristics. Age and gender are typically
      used as the primary cohort-defining attributes, but more complex exposure models
      also use weather, day-of-the-week, and employment attributes for this purpose. We
      analyzed all of these attributes and others to determine if statistically
      significant differences exist among them to warrant their being used to define
      distinct cohort groups. We focused our attention mostly on the relationship
      between cohort attributes and the time spent outdoors, indoors, and in motor
      vehicles. Our results indicate that besides age and gender, other important
      attributes for defining cohorts are the physical activity level of individuals,
      weather factors such as daily maximum temperature in combination with months of
      the year, and combined weekday/weekend with employment status. Less important are
      precipitation and ethnic data. While statistically significant, the collective
      set of attributes does not explain a large amount of variance in outdoor, indoor,
      or in-vehicle locational decisions. Based on other research, parameters such as
      lifestyle and life stages that are absent from CHAD might have reduced the amount
      of unexplained variance. At this time, we recommend that exposure modelers use
      age and gender as "first-order" attributes to define cohorts followed by physical
      activity level, daily maximum temperature or other suitable weather parameters,
      and day type possibly beyond a simple weekday/weekend classification.

PMID- 14726944
TI  - Air concentrations of VOCs in portable and traditional classrooms: results of a
      pilot study in Los Angeles County.
AB  - Recent state and federal public school class-size reduction initiatives,
      increased elementary and pre-K enrollment driven by population growth and
      immigration, and limited resources for capital projects, modernization, and
      maintenance at aging schools have increased the prevalence of prefabricated,
      portable classrooms (portables). At present, approximately one of three
      California students are taught in portables, whose use is especially prevalent in
      more populated counties such as Los Angeles, home to the nation's second largest
      school district. Limited data existed on chemical compound air concentrations,
      and thus exposures, inside American public schools. Measurements have been
      limited, usually performed in complaint schools, and varied in sampling protocols
      and analysis methods. To address a school environment and children's health issue
      of present concern, an assessment of public school portables was conducted in Los
      Angeles County. Seven schools in two school districts were recruited, from which
      20 classrooms--13 portables, seven in main buildings--were randomly selected. We
      report indoor air concentrations of 21 target toxic and odorous volatile organic
      compounds (VOCs), including formaldehyde and acetaldehyde, measured with passive
      samplers (DNSH PAKS and 3M OVM 3500) in the cooling and heating seasons between
      June 2000 and June 2001. None of the measured indoor air formaldehyde
      concentrations exceeded the existing California Air Resources Board guideline (50
      ppb, or 60 microg/m(3)). The main sources of aldehydes in classrooms, especially
      portables, were likely interior finish materials and furnishings made of
      particleboard without lamination. Indoor air VOC concentrations were generally
      low in this pilot study. The four most prevalent VOCs measured were toluene, m-/p
      xylene, alpha-pinene, and delta-limonene; likely indoor sources were personal,
      teaching, and cleaning products. Future schools research should attempt larger
      samples over larger geographical areas.

PMID- 14726945
TI  - Contribution of locally grown foods in cumulative exposure assessments.
AB  - Both laboratory and field studies confirm the importance of vegetation for
      scavenging semivolatile organic chemicals (SVOCs) from the atmosphere and a
      number of exposure studies have found that the dietary pathway is often a
      significant contributor to cumulative exposure for these chemicals. However,
      little information exists on the atmospheric source-to-dietary intake linkage for
      SVOCs. Because of higher SVOC emissions to urban regions, this linkage is
      particularly important for foods that are grown, distributed and consumed in or
      near urban regions. The food pathway can also contribute to dietary exposure for
      populations that are remote from a pollutant source if the pollutants can migrate
      to agricultural regions and subsequently to the agricultural commodities
      distributed to that population. We use available data, the characteristic travel
      distance, and the CalTOX multimedia model framework to assess the contribution of
      local sources of food to cumulative SVOC intake. Based on published concentration
      data for foods, our exposure calculations indicate that the potential intake
      through ingestion can be up to 1000 times that of inhalation for certain
      persistent SVOCs. We use the population-based intake fraction (iF) to determine
      how SVOC intake can vary among food commodities and exposure pathways, and to
      determine the contribution of airborne emitted SVOCs to the diet in the Northern
      Hemisphere. We focus on three representative multimedia SVOCs-benzo(a)pyrene,
      fluoranthene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. The approach presented
      here provides a useful framework and starting point for source-to-intake
      assessments for the ambient air-to-dietary exposure pathway.

PMID- 14726946
TI  - Comparison of pesticide levels in carpet dust and self-reported pest treatment
      practices in four US sites.
AB  - Epidemiologic studies have used both questionnaires and carpet dust sampling to
      assess residential exposure to pesticides. The consistency of the information
      provided by these two approaches has not been explored. In a population-based
      case-control study of non-Hodgkin's lymphoma, carpet dust samples were collected
      from the homes of 513 control subjects in Detroit, Iowa, Los Angeles, and
      Seattle. The samples were taken from used vacuum cleaner bags and analyzed for 30
      pesticides. Interviewers queried subjects about the types of pests treated in
      their home using a detailed questionnaire accompanied by visual aids. Geographic
      variations in pesticide levels were generally consistent with geographic
      differences in pest treatment practices. Los Angeles residents reported the most
      treatment for crawling insects, fleas/ticks, and termites, and Los Angeles dust
      samples had the highest levels of propoxur, chlorpyrifos, diazinon, permethrin,
      and chlordane. Iowa had the most treatment for lawn/garden weeds, and also the
      highest levels of 2,4-dichlorophenoxyacetic acid and dicamba. Although Seattle
      had the highest proportion of subjects treating for lawn/garden insects, the
      lawn/garden insecticides were higher in other sites. Multivariate linear
      regression revealed several significant associations between the type of pest
      treated and dust levels of specific pesticides. The strongest associations were
      between termite treatment and chlordane, and flea/tick treatment and permethrin.
      Most of the significant associations were consistent with known uses of the
      pesticides; few expected associations were absent. The consistency between the
      questionnaire data and pesticide residues measured in dust lends credibility to
      both methods for assessing residential exposure to pesticides. The combined
      techniques appear promising for epidemiologic studies. Interviewing is the only
      way to assess pesticide exposures before current carpets were in place. Dust
      sampling provides an objective measure of specific compounds to which a person
      may have been exposed through personal use of a pesticide or by drift-in or track
      in from outside, and avoids recall bias.

PMID- 14726947
TI  - Identification of responsible volatile chemicals that induce hypersensitive
      reactions to multiple chemical sensitivity patients.
AB  - Multiple chemical sensitivity (MCS) has become a serious problem as a result of
      airtight techniques in modern construction. The mechanism of the MCS, however,
      has not been clarified. Responsible chemicals and their exposure levels for
      patient's hypersensitive reactions need to be identified. We measured the
      exposure of 15 MCS patients to both carbonyl compounds and volatile organic
      compounds (VOCs) that may induce hypersensitive reactions. The exposures of those
      not suffering from MCS (non-MCS individuals) were also measured at the same time.
      To characterize the chemicals responsible for MCS symptoms, we applied a new
      sampling strategy for the measurement of carbonyls and VOCs using active and
      passive sampling methods. The results of our study clearly demonstrated that the
      chemicals responsible for such hypersensitive reactions varied from patient to
      patient. Moreover, the concentrations during hypersensitive symptoms, which were
      apparent in some of the MCS patients, were far below both the WHO and the
      Japanese indoor guidelines. The average exposure levels of MCS patients within a
      7-day period were lower than those of paired non-MCS individuals except for a few
      patients who were exposed to chemicals in their work places. This result
      indicates that the MCS patients try to keep away from exposures to the chemical
      compounds that cause some symptoms.

PMID- 14726948
TI  - Variability of environmental exposures to volatile organic compounds.
AB  - Although studies of occupational exposure to volatile organic compounds (VOCs)
      often partition variability across groups, and between and within persons, those
      of environmental exposure to VOCs have not involved such partitioning. Using data
      from the Environmental Protection Agency's total exposure assessment methodology
      (TEAM) studies, we partitioned exposure variability across cities, and between
      and within persons for nine VOCs. The estimated variance components decreased in
      the order: within-person > between-person > across city. Despite their smaller
      magnitudes, estimates of between-person and across-city variance components were
      sufficiently large to provide reasonable contrast for informative epidemiology
      studies of most VOCs. Estimates of between-person variance components for
      environmental VOCs were similar to those published for occupational VOCs (groups
      defined by job and factory). However, estimates of within-person variance
      components were much greater for environmental VOCs, probably due to the greater
      diversity of locations (including the workplace) visited by the general public
      over time. For benzene and perchloroethylene, we used a simple model to calculate
      numbers of personal measurements required to relate the exposure level to health
      outcome statistically. About 10 times more personal measurements would be
      required to investigate perchloroethylene exposure as compared to benzene
      exposure; this disparity reflects the greater within-subject variability of
      perchloroethylene data compared to benzene data. We conclude that variability
      should be partitioned for environmental VOC exposures in much the same manner as
      for occupational exposures. There should be sufficient variability in the levels
      of most VOCs across cities and between subjects to provide reasonable contrast
      for informative epidemiology studies, as we illustrate for exposures to benzene.
      Yet, epidemiologists should be wary of investigating environmental VOCs without
      preliminary data with which to estimate the variance structure of exposure
      variables.

PMID- 14726950
TI  - Conditional gene knock-down by CRE-dependent short interfering RNAs.
AB  - Short interfering RNAs (siRNAs) are short (21-23 nt) double-stranded RNAs that
      direct the sequence-specific degradation of corresponding mRNAs, resulting in
      suppression of gene activity. siRNAs are powerful tools for gene functional
      analysis in mammals. Chemically synthesized siRNAs permit transient gene
      repression but preclude inhibition of stable gene products as well as long-term
      phenotypic analyses. Permanent gene suppression can be achieved by transcribing
      siRNAs as stem-loop precursors from Pol III promoters. This approach, however,
      has a major limitation: inhibition cannot be controlled in a time- or tissue
      specific manner. Thus, the approach cannot be applied to genes essential for cell
      survival or cell proliferation. To overcome these limitations, we have designed a
      CRE-lox-based strategy that allows one to repress gene activity in a time
      dependent manner in cells, and in a time- or tissue-dependent manner in animals.
      Our approach promises to improve dramatically the procedures for functional
      genetics in mammals.

PMID- 14726951
TI  - Yeast N-glycanase distinguishes between native and non-native glycoproteins.
AB  - N-glycanase from Saccharomyces cerevisiae (Png1) preferentially removes N-glycans
      from misfolded proteins. The ability of Png1 to distinguish between folded and
      misfolded glycoproteins is reminiscent of substrate recognition by UDP-glucose
      glycoprotein glucosyl transferase, an enzyme that possesses this trait. The only
      known in vivo substrates of Png1 are aberrant glycoproteins that originate in the
      endoplasmic reticulum, and arrive in the cytoplasm for proteasomal degradation.
      The substrate specificity of Png1 is admirably suited for this task.

PMID- 14726952
TI  - In vivo analysis of the overlapping functions of DnaK and trigger factor.
AB  - Trigger factor (TF) is a ribosome-bound protein that combines catalysis of
      peptidyl-prolyl isomerization and chaperone-like activities in Escherichia coli.
      TF was shown to cooperate with the DnaK (Hsp70) chaperone machinery in the
      folding of newly synthesized proteins, and the double deletion of the
      corresponding genes (tig and dnaK) exhibited synthetic lethality. We used a
      detailed genetic approach to characterize various aspects of this functional
      cooperation in vivo. Surprisingly, we showed that under specific growth
      conditions, one can delete both dnaK and tig, indicating that bacterial survival
      can be maintained in the absence of these two major cytosolic chaperones. The
      strain lacking both DnaK and TF exhibits a very narrow temperature range of
      growth and a high level of aggregated proteins when compared to either of the
      single mutants. We found that, in the absence of DnaK, both the N-terminal
      ribosome-binding domain and the C-terminal domain of unknown function are
      essential for TF chaperone activity. In contrast, the central PPIase domain is
      dispensable. Taken together, our data indicate that under certain conditions,
      folding of newly synthesized proteins in E. coli is not totally dependent on an
      interaction with either TF and/or DnaK, and suggest that additional chaperones
      may be involved in this essential process.

PMID- 14726953
TI  - Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory
      protein 2 dominates iron homeostasis.
AB  - The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin,
      transferrin receptor and other target genes to control the expression of iron
      metabolism proteins at the post-transcriptional level. Here we compare the
      effects of genetic ablation of IRP1 to IRP2 in mice. IRP1-/- mice misregulate
      iron metabolism only in the kidney and brown fat, two tissues in which the
      endogenous expression level of IRP1 greatly exceeds that of IRP2, whereas IRP2-/-
      mice misregulate the expression of target proteins in all tissues. Surprisingly,
      the RNA-binding activity of IRP1 does not increase in animals on a low-iron diet
      that is sufficient to activate IRP2. In animal tissues, most of the bifunctional
      IRP1 is in the form of cytosolic aconitase rather than an RNA-binding protein.
      Our findings indicate that the small RNA-binding fraction of IRP1, which is
      insensitive to cellular iron status, contributes to basal mammalian iron
      homeostasis, whereas IRP2 is sensitive to iron status and can compensate for the
      loss of IRP1 by increasing its binding activity. Thus, IRP2 dominates post
      transcriptional regulation of iron metabolism in mammals.

PMID- 14726954
TI  - Sin mutations alter inherent nucleosome mobility.
AB  - Previous studies have identified sin mutations that alleviate the requirement for
      the yeast SWI/SNF chromatin remodelling complex, which include point changes in
      the yeast genes encoding core histones. Here we characterise the biochemical
      properties of nucleosomes bearing these mutations. We find that sin mutant
      nucleosomes have a high inherent thermal mobility. As the SWI/SNF complex can
      alter nucleosome positioning, the higher mobility of sin mutant nucleosomes
      provides a means by which sin mutations may substitute for SWI/SNF function. The
      location of sin mutations also provides a new opportunity for insights into the
      mechanism for nucleosome mobilisation. We find that both mutations altering
      histone DNA contacts at the nucleosome dyad and mutations in the dimer-tetramer
      interface influence nucleosome mobility. Furthermore, incorporation of H2A.Z into
      nucleosomes, which also alters dimer-tetramer interactions, affects nucleosome
      mobility. Thus, variation of histone sequence or subtype provides a means by
      which eukaryotes may regulate access to chromatin through alterations to
      nucleosome mobility.

PMID- 14726955
TI  - Physical and functional interactions between nucleotide excision repair and DNA
      damage checkpoint.
AB  - The mechanisms used by checkpoints to identify DNA lesions are poorly understood
      and may involve the function of repair proteins. Looking for mutants specifically
      defective in activating the checkpoint following UV lesions, but proficient in
      the response to methyl methane sulfonate and double-strand breaks, we isolated
      cdu1-1, which is allelic to RAD14, the homolog of human XPA, involved in lesion
      recognition during nucleotide excision repair (NER). Rad14 was also isolated as a
      partner of the Ddc1 checkpoint protein in a two-hybrid screening, and physical
      interaction was proven by co-immunoprecipitation. We show that lesion recognition
      is not sufficient for checkpoint activation, but processing, carried out by
      repair factors, is required for recruiting checkpoint proteins to damaged DNA.
      Mutations affecting the core NER machinery abolish G1 and G2 checkpoint responses
      to UV, preventing activation of the Mec1 kinase and its binding to chromosomes.
      Conversely, elimination of transcription-coupled or global genome repair alone
      does not affect checkpoints, suggesting a possible interpretation for the
      heterogeneity in cancer susceptibility observed in different NER syndrome
      patients.

PMID- 14726956
TI  - Competition of CUGBP1 and calreticulin for the regulation of p21 translation
      determines cell fate.
AB  - Induction of p21 in senescent human fibroblasts plays a key role in the
      inactivation of cyclin-dependent kinases and the resulting irreversible growth
      arrest in the early stages of cell senescence. We found that RNA-binding proteins
      are critical regulators of p21 during senescence. Two RNA-binding proteins,
      CUGBP1 and calreticulin (CRT), interact with the same nucleotide sequences within
      the 5' region of p21 mRNA, but have opposite effects on the translation of p21
      mRNA. CUGBP1 increases translation of p21 mRNA, whereas CRT blocks translation of
      p21 via stabilization of a stem-loop structure within the 5' region of the p21
      mRNA. CUGBP1 and CRT compete for binding to p21 mRNA and thereby the regulation
      of p21 translation. In senescent fibroblasts, CUGBP1 displaces CRT from the p21
      mRNA and releases CRT-dependent repression of p21 translation leading to growth
      arrest and development of a senescent phenotype. These data present evidence that
      competition between RNA-binding proteins for the regulation of p21 translation
      determines cell fate.

PMID- 14726958
TI  - Conditionally replicative adenovirus driven by the human telomerase promoter
      provides broad-spectrum antitumor activity without liver toxicity.
AB  - The human telomerase reverse transcriptase (hTERT) promoter is known to
      selectively drive transgene expression in many human cancer cells expressing
      hTERT, the catalytic component of the telomerase ribonucleoprotein complex. We
      have created a conditionally replicative adenovirus where the viral E1A gene,
      which is required for viral replication, is under the control of the hTERT
      promoter (AdhTERTp-E1A). In vitro studies with AdhTERTp-E1A virus on a variety of
      normal and tumor cell lines have shown that viral genome replication and
      productive infection is primarily restricted to telomerase-positive tumor cells.
      Lytic replication was not observed in normal primary fibroblast and epithelial
      cell lines tested. In vivo administration of the virus into nude mice bearing
      human liver or prostate tumor xenografts produced significant tumor reduction
      and, in some cases, resulted in complete tumor regression. AdhTERTp-E1A virus did
      not actively express E1A in normal mouse liver, in contrast to a control
      oncolytic vector in which the CMV promoter (AdCMVp-E1A) was driving the E1A gene.
      In addition, AdhTERTp-E1A virus produced no apparent toxicity to the liver in
      systemically injected mice. The hTERT promoter-driven oncolytic virus also
      produced significantly less toxicity to freshly cultured human hepatocytes. These
      studies demonstrate that an oncolytic virus driven by the telomerase promoter can
      be used to effectively kill a wide variety of cancer cell types and has the
      potential to treat primary and metastatic cancer of diverse origins.

PMID- 14726957
TI  - The Arabidopsis homologue of Xrcc3 plays an essential role in meiosis.
AB  - The eukaryotic RecA homologue Rad51 is a key factor in homologous recombination
      and recombinational repair. Rad51-like proteins have been identified from yeast
      (Rad55, Rad57 and Dmc1) to vertebrates (Rad51B, Rad51C, Rad51D, Xrcc2, Xrcc3 and
      Dmc1). These Rad51-like proteins are all members of the genetic recombination and
      DNA damage repair pathways. The sequenced genome of Arabidopsis thaliana encodes
      putative homologues of all six vertebrate Rad51-like proteins. We have identified
      and characterized an Arabidopsis mutant defective for one of these, AtXRCC3, the
      homologue of XRCC3. atxrcc3 plants are sterile, while they have normal vegetative
      development. Cytological observation shows that the atxrcc3 mutation does not
      affect homologous chromosome synapsis, but leads to chromosome fragmentation
      after pachytene, thus disrupting both male and female gametogenesis. This study
      shows an essential role for AtXrcc3 in meiosis in plants and possibly in other
      higher eukaryotes. Furthermore, atxrcc3 cells and plants are hypersensitive to
      DNA-damaging treatments, supporting the involvement of this Arabidopsis Rad51
      like protein in recombinational repair.

PMID- 14726959
TI  - Chemokine gene modification of human dendritic cell-based tumor vaccines using a
      recombinant adenoviral vector.
AB  - Previous animal studies conducted in our laboratory have shown that tumor antigen
      pulsed dendritic cells (TP-DC) can mediate antitumor effects in vivo. However,
      durable and complete regression of established tumors has been difficult to
      achieve through the administration of TP-DC alone. To better augment immune
      priming to tumors in vivo, we have hypothesized that it is necessary to achieve
      an increased number of host-derived, naive T cells at the site of TP-DC vaccine
      injections. To accomplish this goal, we have embarked on a series of studies that
      utilize defined chemokines. One of these molecules, secondary lymphoid tissue
      chemokine (SLC), has been shown to be uniquely chemoattractant for naive T cells
      and dendritic cells. We propose that gene modification of DC-based tumor vaccines
      to produce human SLC will enhance T-cell recruitment and immune priming to tumor
      associated antigens, and thereby translate into improved antitumor vaccine
      efficacy in vivo. Utilizing an E1-, E3-deleted adenoviral vector containing the
      gene for human SLC, we have been able to transduce human DC to produce
      biologically active human SLC that chemoattracts human T cells in vitro. SLC
      production by transduced DC was markedly enhanced upon DC maturation.
      Additionally, these SLC-secreting DC were found to be viable to a large extent
      despite the cytopathic effect inherent in adenoviral gene transfer and, most
      importantly, functional as determined by their ability to prime autologous T
      cells to a known melanoma-associated antigen, MART-1. Based on these encouraging
      results, we plan to initiate Phase I clinical studies utilizing DC-SLC to treat
      patients with advanced solid tumors.

PMID- 14726960
TI  - Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with
      dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35
      fiber.
AB  - Delivery of the full-length tumor antigen might be more successful in
      immunotherapy than single peptides and has the advantage that patients no longer
      need to be selected for their HLA type. In this study, we tested the in vitro
      induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with
      an adenovirus (Ad) type 5 vector containing the fiber shaft and knob of human
      serotype Ad35 (Ad5F35 vector). Our data show induction of CD8(+) T cells specific
      for the known HLA-A(*)0201-binding CAMEL/NY-ESO-ORF2(1-11) epitope by DC infected
      with Ad5F35-CAMEL, but not by DC pulsed with the recombinant CAMEL protein. In
      one healthy donor, even CD8(+) T cells specific for a new HLA-B7-binding CAMEL/NY
      ESO-ORF2(46-54) epitope were raised. In conclusion, the in vitro induction of
      CAMEL/NY-ESO-ORF2-specific CD8(+) T cells in healthy donors by DC infected with
      Ad5F35-CAMEL strongly supports further investigation of the Ad5F35 vector as a
      vehicle for gene transfer into DC for the generation of tumor antigen-specific
      CD8(+) T cell responses in vivo.

PMID- 14726962
TI  - Granzyme B-mediated apoptosis--the elephant and the blind men?

PMID- 14726961
TI  - A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for
      epithelial cell death.
AB  - Oxidative stress releases intracellular calcium, which plays a pathogenic role in
      mammalian cell death. Here we report a search for the source of oxidative calcium
      in HeLa cells based on confocal epifluorescence microscopy. H(2)O(2) caused a
      rapid increase in cytosolic calcium, which was followed by mitochondrial Ca(2+)
      loading. Combined mitochondrial uncoupling with full depletion of thapsigargin
      sensitive stores abrogated inositol 1,4,5-trisphosphate-mediated calcium release
      but failed to inhibit H(2)O(2)-induced calcium release, observation that was
      confirmed in MDCK cells. Prevention of peroxide-induced acidification with a pH
      clamp was also ineffective, discarding a role for endosomal/lysosomal Ca(2+)/H(+)
      exchange. Lysosomal integrity was not affected by H(2)O(2). Mature human
      erythrocytes also reacted to peroxide by releasing intracellular calcium, thus
      directly demonstrating the cytosolic source. Glutathione depletion markedly
      sensitized cells to H(2)O(2), an effect opposite to that achieved by DTT. Iron
      chelation was ineffective. In summary, our results show the existence of a
      previously unrecognized sulfhydryl-sensitive source of pathogenic calcium in the
      cytosol of mammalian cells.

PMID- 14726963
TI  - Pathophysiological functions of CD30+ CD4+ T cells in rheumatoid arthritis.
AB  - High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid
      of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T
      cells in the pathogenesis. We investigated the induction of CD30 and its
      functions in CD4+T cells from patients with established RA (disease duration >_2
      years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST)
      of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab)
      and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB
      CD4+ T cells of healthy controls (HC). Immunohistochemical analysis showed that
      only a small proportion of lymphocytes expressed CD30 in the ST (-1%). RA PB CD4+
      T cells, after recovery from 6-day stimulation with anti-CD3 Ab and anti-CD28 Ab,
      showed in intracellular cytokine staining that CD30+ T cells could produce more
      interleukin-4 (IL-4) but less interferon-gamma. In the culture of RA PB CD4+ T
      Cells with anti-CD3 Ab and anti-CD28 Ab, blocking anti-CD30 Ab similarly
      inhibited the cell proliferation and activation of nuclear factor-kappaB on day 4
      in RA and HC, but inhibited the apoptotic cell death on day 6 only in RA. These
      results indicate that despite high-level expression of sCD30, the anti
      inflammatory activity of IL-4-producing CD30+ CD4+ T cells may be limited in the
      ST due to a poor induction of surface CD30 and a susceptibility to CD30-mediated
      cell death.

PMID- 14726964
TI  - CD56-positive cells with or without synaptophysin expression are recognized in
      the pancreatic duct epithelium: a study with adult and fetal tissues and
      specimens from chronic pancreatitis.
AB  - We observed the distribution of CD56+ epithelial cells in the pancreatic duct
      system using 25 fetal, one infantile, 3 normal adult, 4 diabetic, and 8
      chronically inflamed pancreatic tissue samples. In the early stage of gestation
      (12 to 17 weeks), CD56+ cells were commonly seen in the immature tubular
      structures. They were often continuous to pancreatic islets, and their
      distribution was similar to that of synaptophysin (Syn)+ cells, suggesting that
      they are precursors of islet neogenesis. Their number decreased in proportion to
      gestational age. Instead, from 24 weeks of gestation, luminal cell clusters that
      were common in interlobular ducts revealed CD56+. These cell clusters were
      unrelated to islet neogenesis and Syn expression. Similar CD56+ luminal cell
      clusters were also observed in cases of chronic pancreatitis, whereas they were
      scarce in normal adult and diabetic tissues. CD56+ cells were also occasionally
      seen in intralobular ducts, intercalated ducts, and centroacinar cells in cases
      of chronic pancreatitis. We conclude that there are two types of CD56+ epithelial
      cells in the pancreatic duct system: CD56+ endocrine cells are numerous during
      the early stage of gestation, when islet neogenesis appears, while CD56+ luminal
      cells may represent developmental and regenerative changes of pancreatic ducts.

PMID- 14726965
TI  - Effects of pulsing procedure of interleukin-12 in combination with interleukin-2
      on the activation of peripheral blood lymphocytes derived from patients with
      hepatocellular carcinoma.
AB  - In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell
      activity decreases significantly, and the reduced activity may be associated with
      the progression of HCC. In this study we evaluated the effects of pulsing with
      interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral
      blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC
      patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the
      presence of IL-2 and/or IL-12. After 24 h of incubation, the levels of interferon
      (IFN)-gamma and tumor necrosis factor (TNF)-alpha presented in the supernatants
      were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-gamma and
      TNF-alpha production of PBL pulsed by a combination of IL-2 and IL-12 was
      significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone.
      The mRNA encoding perforin, granzyme B, as well as IFN-gamma and TNF-alpha, were
      markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The
      pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of
      IFN-gamma and TNF-alpha, and the expression of perforin and granzyme B mRNA in
      PBL obtained from HCC patients, as well as in those obtained from normal
      subjects. These results indicate that adoptive immunotherapy based on PBL pulsed
      with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for
      HCC treatment.

PMID- 14726966
TI  - Anterior urethral recurrence of superficial bladder cancer: its clinical
      significance.
AB  - The aim of this study was to reveal the clinical features of anterior urethral
      recurrence in patients with superficial bladder cancer, and to determine the
      appropriate treatment. Three hundred and three patients with superficial bladder
      cancer, who were newly diagnosed and initially treated conservatively in our
      hospital between 1965 and 1990, were followed for at least 5 years and their
      clinical outcomes were analyzed. Clinical factors, including anterior urethral
      recurrence, were evaluated statistically regarding tumor progression. Eight
      patients (2.6%) had anterior urethral recurrence following superficial bladder
      cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had
      tumor recurrence. In a multivariate analysis using a logistic model, anterior
      urethral recurrence was the most important factor, followed by histological
      grade. Four of 5 patients who were treated for anterior urethral recurrent tumors
      by transurethral resection showed progression and died of the cancer within one
      year. Two of the remaining three patients who underwent radical cysto
      urethrectomy at the time of anterior urethral recurrence survived. Anterior
      urethral recurrence following superficial bladder cancer is a predictor for rapid
      subsequent malignant progression. Once there is anterior urethral recurrence,
      radical intensive therapy, including radical cysto-urethrectomy, should be
      carried out immediately.

PMID- 14726967
TI  - Ocular anterior segment pathologies and tear film changes in patients with
      psoriasis vulgaris.
AB  - Ocular manifestations in patients with psoriasis vulgaris have been investigated
      in only a small number of studies. Our purpose was to identify tear film function
      and ocular pathologies associated with psoriasis vulgaris in patients who had
      received neither oral retinoids nor phototherapy. We examined 62 eyes of 31
      patients with psoriasis and 60 eyes of 30 age-and-sex matched healthy volunteers.
      In addition to complete ocular and dermatological examination, tear film function
      (i.e., tear secretion and tear film stability) were assessed by the Schirmer-I
      test, as well as by tear film break-up time. None of the controls had any ocular
      abnormalities, whereas 67.74% of patients with psoriasis had various anterior
      segment pathologies (P<0.00009). The most prevalent finding was chronic
      blepharoconjunctivitis (64.5%), as the only pathology (n=9) or in association
      with other findings, including nonspecific corneal opacities (n=4), cataract
      (n=3), both corneal opacities and cataract (n=2), and corneal pigment dispersion
      (n=2). The Schirmer-I test results revealed comparable mean values in the patient
      group (9.8+-4.2 mm) and in the controls (11.2+-3.7 mm; P=0.078). However, mean
      tear film break-up time was significantly shorter in the patients (7.2+-2.5 sec)
      than in the healthy persons (11.7+-3.1 sec; P=0.001). In agreement with some
      previous reports, our findings clearly demonstrated that early ocular involvement
      occurs in patients with psoriasis vulgaris, irrespective of the history of
      previous therapeutic modalities (e.g., retinoid therapy and phototherapy). Thus,
      the present findings are suggestive of the contributory role of primary etiologic
      factors of psoriasis in the pathogenesis of ocular changes in patients with
      psoriasis vulgaris.

PMID- 14726968
TI  - A new mutation of LKB1 gene in a Japanese patient with Peutz-Jeghers syndrome.
AB  - Germline mutations of the LKB1 gene are associated with Peutz-Jeghers syndrome
      (PJS), which is characterized by mucocutaneous pigmentation and gastrointestinal
      hamartoma with an increased risk of cancer development. In this study, we have
      employed polymerase chain reaction and DNA sequencing analysis to characterize
      the LKB1 gene in a 25-year-old Japanese PJS patient. Direct sequence analyses
      revealed a novel single base deletion at nucleotide 844 in exon 6 (844delC) in
      one LKB1 allele, resulting in a frame shift and in the introduction of a
      premature termination codon in this mutated allele.

PMID- 14726969
TI  - Aspects of immune nonspecific and CD19+ cell changes in alcoholic liver disease
      with or without chronic hepatitis C virus infection.
AB  - BACKGROUND AND AIM: The incidence of hepatitis C infection is high in alcoholics.
      The aim of our study was to evaluate the immune nonspecific cell and the humoral
      mediated disorders in alcoholic liver disease (ALD) associated or not with
      chronic hepatitis C. MATERIAL AND METHODS: We selected 20 heavy drinkers (intake 
      over 80g ethanol/day for more than 10 years) with (8 patients) and without (12
      patients) chronic viral C hepatitis. Besides the diagnostic tests including liver
      biopsy, hemoleucogram (leukocyte formula), serum iron level, protein
      electrophoresis were performed in all patients, as well as cryoglobulins,
      rheumatoid factor (RF), immunoglobulins, antinuclear autoantibodies and
      circulating immune complexes. The circulating B cells with positive CD19 markers
      (LyB CD19+) were evaluated by flow cytometry. RESULTS: All patients had
      reversible neutropenia and thrombocytopenia. The values of LyB CD19+ were low in
      all patients. All patients had similar IgG levels. The RF, cryoglobulins and
      autoantibodies were absent in the group of patients with ALD and HCV infection.
      CONCLUSION: The values of LyB are low in ALD with or without HCV infection. The
      markers of autoimmunity (RF) or of B cell proliferation (cryoglobulins) were
      absent in patients with ALD and HCV infection. Although HCV is a lymphotrophic
      virus, the presence of HCV had no permissive effect on the proliferation of LyB
      in ALD, probably due to the depressive effect of chronic alcohol intake on LyB.

PMID- 14726970
TI  - Intravenous midazolam sedation in pediatric diagnostic upper digestive endoscopy.
      A prospective study in a general hospital.
AB  - The positive role of benzodiazepines (Midazolam) in conscious sedation in
      pediatric patients is widely known. However, problems concerning the role of
      sedation in diagnostic upper endoscopy are a matter for debate as little is known
      about dosage and timing. We prospectively evaluated the efficacy, safety and
      optimal intravenous sedation dosage of midazolam in 257 consecutive patients,
      aged 2 months to 18 years old, who underwent upper endoscopy of the
      gastrointestinal tract. The initial midazolam dosage was 0.2 mg/kg Bw (Body
      weight) i.v. for 1 minute and, if necessary, another 0.1 mg/kg Bw was
      administered 5 minutes later. If sedation was sufficient, the procedure would be
      started 4-5 minutes later; if not, another 0.1 - 0.2 mg/kg Bw would be
      administered. All procedures were performed by a pediatrician together with a
      gastroenterologist. No serious complications occurred in any of the procedures.
      Oxygen saturation (OS) was maintained at over 90%, if necessary with blowby
      oxygen. Flumazenil was administered to 7 children (OS < 90%). Endoscopy could not
      be completed in 1 child. All endoscopies were completed within 10 minutes. No
      unexpected hospital admissions were necessary. The mean midazolam dosage was 0.4
      mg/kg Bw in patients up to 6 years, for the over 6 years-olds the mean dosage was
      decreased to 0,2 mg/kg Bw. Particular attention was paid to the importance of
      informing patients before the procedure. Endoscopic diagnostic procedures can be
      performed safely and effectively in children with intravenous sedation in a well
      equipped pediatric endoscopy unit.

PMID- 14726971
TI  - Color Doppler transabdominal ultrasonography for the assessment of the patients
      with inflammatory bowel disease during treatment.
AB  - Color and power Doppler ultrasound are useful methods for the assessment of
      patients with gastrointestinal diseases. The aim of our study was to assess color
      Doppler and power Doppler ultrasound, during the evolution of patients with
      ulcerative colitis and Crohn's disease treated with salazopyrin. We included in
      the study 10 patients with inflammatory bowel diseases diagnosed by colonoscopy
      with multiple biopsies. All the patients underwent color and power Doppler
      ultrasound using Jeffrey criteria for the evaluation of intestinal vasculature.
      Biological examinations included: erythrocyte sedimentation rate, serum C
      reactive protein, blood cell count, fibrinogenemia, protein electrophoresis and
      immunoelectrophoresis. The results of our study indicated a diminished blood flow
      at the level of the affected intestinal segments after one month of salazopyrin
      treatment. Color and power Doppler ultrasound might thus represent a useful
      method for monitoring the response in inflammatory bowel disease treatment.

PMID- 14726972
TI  - Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients
      with ulcerative colitis: the old and new evidence.
AB  - BACKGROUND: The purpose of the study was to assess whether folic acid
      supplementation and long term therapy with sulfasalazine can reduce the risk of
      colorectal cancer (CRC) development in longstanding extensive ulcerative colitis.
      MATERIAL AND METHODS: A meta-analysis was performed including the last 10 years
      published and Medline indexed studies on this subject. RESULTS: 3 studies have
      been included concerning the protective effect of folate supplementation in
      development of CRC. The association of these two factors is significant (effect
      size r =0.124, p = 0.025). The fail-safe number of studies with an opposite
      result should be 4 to revert the significance. 4 studies regarding
      sulfasalazine's protective effect in longstanding extensive ulcerative colitis
      have also been evaluated. A similar significance has been obtained, r = 0.148, p
      = 0.0007 and a fail-safe number of studies equal to 7. The homogeneity of these
      studies is validated by standard tests. CONCLUSIONS: Both sulfasalazine therapy
      and folate supplementation have a protective effect in colorectal cancer
      development in a population of patients with longstanding ulcerative colitis.
      Randomized controlled trials are needed to explore these hypotheses.

PMID- 14726973
TI  - Anal fistulotomy with radiofrequency: a better option to a conventional
      procedure.
AB  - BACKGROUND: Even after the availability of many different surgical options, most
      surgeons still prefer the classical lay open technique (fistulotomy) as the gold
      standard for the treatment of anal fistula. This study analyzes the procedure and
      outcome of radiofrequency fistulotomy over the conventional scalpel method.
      MATERIAL AND METHODS: Fifty patients with low fistula in ano were analyzed in a
      prospective study. They were randomized into conventional and radiofrequency
      fistulotomy groups. Parameters measured included time taken for the procedure,
      amount of blood loss, postoperative pain, period taken for return to work and
      recurrence rate. The patients were followed over a period of 30 months. RESULTS:
      The average time for complete wound healing was 49 days. The patients took a mean
      period of 7 days to return to their routine. In 7 patients the wounds took more
      than 80 days to heal and were labeled as delay in wound healing. Two patients
      developed a recurrence. The comparative study between conventional and
      radiofrequency fistulotomy showed that procedure time was shorter (p= 0.001);
      intra operative bleeding was much less (p=0.0004), return to work was earlier (p=
      0.029) and wound-healing time was shorter (p=0.0017) in radiofrequency procedure.
      CONCLUSION: In terms of parameters set for the study, the radiofrequency
      technique was found to have significant advantages over conventional fistulotomy
      procedure with regard to operation time, blood loss, return to normal activity
      and healing of the wounds.

PMID- 14726974
TI  - Helicobacter pylori colonization in dental plaque and gastric infection.
AB  - BACKGROUND: With regard to the presence of Helicobacter pylori (H.pylori ) in
      dental plaque and its association with gastric infection, data from the
      literature are controversial. The aim of this study was to determine the
      prevalence of H.pylori in dental plaque of dyspeptic patients who underwent upper
      gastrointestinal endoscopy and to investigate its relationship to gastric
      infection. METHODS: In a cross sectional study, over one year ( February 2002
      February 2003) samples were taken with separate sterile curretes from tooth
      surfaces of molars, premolars and incisors of 180 consecutive dyspeptic patients
      referred to the Endoscopy Department of Emmam Khomeini Hospital. Dental plaque
      samples were subjected to the rapid urease test, Giemsa staining, PCR test and
      culture for identification of H.pylori. During endoscopy, six biopsies were taken
      from the gastric antrum and corpus and histological examination, Giemsa
      stainings, Rapid Urease test and culture were performed. Patients were defined as
      infected when both rapid urease test and Giemsa stain, or when cultures were
      positive for H.pylori. Information concerning oral hygiene protocol were
      recorded. For data analysis, the chi square test was used and P < 0.05 was
      defined statistically significant. RESULTS: Our data proved the presence of H.
      pylori in dental plaque of infected and uninfected patients. There was no
      significant association between H. pylori colonization in dental plaque and
      gastric infection. In this study, oral hygiene (the frequency of dental visits
      and teeth cleaning) did not have a significant influence on the presence of H.
      pylori in dental plaque. CONCLUSION: Dental plaque is the reservoir of H.pylori
      with no relationship to gastric infection.

PMID- 14726975
TI  - Cirrhosis and bacterial infections.
AB  - Half of cirrhosis patients die within two years after diagnosis, in most cases
      from cirrhosis related causes; most frequently variceal bleeding closely followed
      by infections. There seems to exist associations between infection and other
      complications such as malnutrition, hepatic encephalopathy and variceal bleeding.
      Cirrhosis patients have an acquired immune deficiency because of dyshomeostasis
      and malnutrition. All host defence systems are compromised, e.g. the acute phase
      response, and macrophage, neutrocyte, and lymphocyte functions. Simultaneously,
      there is increased microbiotic invasion, due to increased nosocomial exposure,
      intestinal translocation, aspiration, skin lesions, and trauma. Compared to the
      background population, the mortality of infections is more than 20 times
      increased in cirrhosis. The incidence of peritonitis, bacteremia, urinary tract
      infection, pneumonia, meningitis, tuberculosis, liver abscess is increased more
      than tenfold, and the mortality of each episode 3-10 times higher. The systemic
      response and accompanying classical symptoms are usually weakened. When positive
      isolates can be obtained the flora tends to be of an opportunistic nature.
      Infection should be suspected in any cirrhotic patient with an unexpected
      deterioration of clinical course. Treatment should be started on suspicion and
      with large dose broad-spectrum antibiotics (avoiding aminoglycosides). Antibiotic
      prophylaxis is efficacious at variceal bleeding, recurrent peritonitis, and at
      very low protein ascites, but otherwise is associated with risk of infection with
      multi-resistant strains.

PMID- 14726976
TI  - An unusual etiology of viral hepatitis in three renal transplant recipients with
      normal graft function.
AB  - Liver impairment in renal transplant recipients is not a common complication and
      is associated, in most cases, with viral infections (HBV, HCV, HVD, HGV) or drug
      hepatotoxicity (Cyclosporin, Azathioprine, statins). Cytomegalovirus (CMV)
      infection is common, with 50 to 80% of the adult population being seropositive
      for CMV antibodies. In immunocompetent individuals, primary infection is usually
      asymptomatic or associated with minor illness. CMV remains latent after primary
      infection. In immunocompromised patients, as in renal transplant recipients or
      transplant recipients of other solid organ or bone marrow, the virus can cause
      serious disease. This could be the result of newly acquired infection or
      reactivation of the latent virus. One of the organs involved in CMV disease is
      the liver. The subjects of this report are renal transplant recipients with liver
      impairment due to CMV induced acute hepatitis.

PMID- 14726977
TI  - Portal biliopathy--a lesser known complication of portal hypertension. Case
      report and review of the literature.
AB  - Portal biliopathy is a newly introduced term, describing the changes observed in
      the biliary ducts of portal hypertension patients. We present here the case of a
      patient diagnosed with portal vein thrombosis secondary to a chronic
      pancreatitis; the abnormalities in the bile ducts were observed during the
      endoscopic retrograde cholangiopancreatography. We also review the existing
      information on this subject in the literature.

PMID- 14726978
TI  - Hydrothorax without ascites in liver cirrhosis.
AB  - Pleural effusion in patients with liver cirrhosis and intractable ascites is well
      known, but hepatic hydrothorax in the absence of ascites is a rare complication.
      We present the case of a 43-year old male, with a medical history of liver
      cirrhosis due to hepatitis C virus, who was admitted to the Pneumology Clinic for
      dyspnoea, worsening of general status and chronic asthenia. The pleural effusion,
      revealed on physical and laboratory examinations, persisted despite the therapy
      with diuretics and the frequent thoracocentesis. The thoracostomy followed by
      pleurodesis also failed. The pecularity of this case was the presence of
      refractory hydrothorax in the absence of ascites.

PMID- 14726979
TI  - Multi-detector row spiral CT (MDCT) in bowel related non-traumatic abdominal
      emergencies.
AB  - The management of the patients with acute abdomen syndrome requires an accurate
      and rapid diagnostic. Spiral CT is the investigation of choice in these cases
      because it is rapid, cost-effective and provides a global perspective of
      abdominal structures. Also, helical CT offers the possibility to obtain thinner
      contiguous images and to perform coronal or sagittal reconstruction, as well as
      the possibility to make the acquisitions during the different vascular phases.

PMID- 14726980
TI  - The prevalence of coeliac disease.

PMID- 14726983
TI  - Acute epiglottitis: MRI.
AB  - We report the MRI findings in an adult with epiglottitis. There was thickening of
      the epiglottis and left aryepiglottic fold. Management of this life-threatening
      condition requires imaging only when the diagnosis is uncertain or when an
      abscess or other complication is suspected.

PMID- 14726982
TI  - MR perfusion imaging in proliferative angiopathy.
AB  - Seizures, which may be the main expression of cerebral arteriovenous
      malformations (CAVM) can be difficult to control medically. Our goal was to use
      perfusion-weighted imaging (PWI) in correlation with clinical data to detect
      abnormal areas of the cerebrum related to a particular type of CAVM
      (proliferative angiopathy) and to study the pathophysiology. We use PWI, with a
      bolus injection of contrast medium, to investigate seven patients with
      proliferative angiopathy and fits producing language disturbance. Perfusion
      parameters were calculated using the first-pass moment theory. Five patients had
      perimalformative and/or contralateral abnormal areas with relative hyperperfusion
      (cerebral blood volume +20.7+/-16.2%, blood flow 92.5+/-68.8 ml/min/100 g). Areas
      of hypoperfusion and venous congestion were detected in two patients. One patient
      who underwent MRI after a severe focal deficit had no significant haemodynamic
      abnormality.

PMID- 14726984
TI  - Reversal of restricted diffusion in cerebral venous thrombosis: case report.
AB  - We report a patient with extensive cerebral venous thrombosis who showed complete
      reversal of restricted diffusion on MRI, accompanied by excellent clinical
      recovery. The implications of these findings in relation to interpretation of
      diffusion changes in cerebral venous thrombosis are discussed, and differences
      with arterial stroke are highlighted.

PMID- 14726985
TI  - Brain abscesses after Serratia marcescens infection on a neonatal intensive care
      unit: differences on serial imaging.
AB  - Serratia are known to be a possible cause of severe cerebral infections in
      neonates. We describe imaging of three premature infants infected with Serratia
      marcescens. Born in the 31( st), 25( th) and 28( th) weeks of gestation, they
      presented with signs of septicaemia on postnatal days 9, 24 and 32. Initial
      sonography showed cysts in the first child, two areas with anechoic centre and
      echogenic rim in the second, and several echogenic areas in the third. Lesions
      were seen on CT, of low density in two cases and minimally increased density in
      the third. MRI in the first patient showed cysts with incomplete contrast
      enhancement of the lesions, while patient 2 showed five ring-enhancing fluid
      containing lesions with thick walls. In the third patient two abscesses with
      contrast enhancement and several high-signal spots were seen. We discuss the
      pathophysiology of the lesions and the impact of the various imaging methods.

PMID- 14726987
TI  - Distractor modulation of saccade trajectories: spatial separation and symmetry
      effects.
AB  - The trajectories of saccadic eye movements can be modulated by the presence of a
      competing visual distractor. In the present study the trajectories of vertical
      saccades curved away from a single visual distractor presented in one visual
      field, but tended to be straight when two distractors were presented at mirror
      symmetric locations in both visual fields. The spatial nature of the mirror
      distractor effect was examined by presenting a second distractor at mirror and
      non-mirror locations. Saccade trajectories also tended to be straight with both
      mirror and non-mirror symmetrical distractors. The relationship between the
      distractor location and saccade curvature was examined in a third experiment by
      manipulating the distractor-to-target spatial separation. Although there was a
      tendency for greater curvature when the distractor was presented in the same
      hemifield as the target there was no clear relationship between curvature and
      distractor location. The results show that the distractor modulation of saccade
      trajectory is not highly spatially specific and that it can be balanced by a
      second bilateral distractor in the opposite visual field. The results are
      interpreted in terms of a model in which the initial saccade direction and
      curvature back towards the saccade goal are controlled by separate processes.
      Initial saccade direction is modulated by the inhibition of distractor locations
      within a 'motor map' specifying saccade direction. Curvature back towards the
      saccade goal may be attributed to a feedback system, with a separate
      representation of the visual target location, that enables an on-line correction
      of the saccade during mid-flight.

PMID- 14726986
TI  - Effect of CYP2D6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma
      concentrations during steady-state conditions.
AB  - OBJECTIVES: CYP2D6 drug-metabolising enzyme has been shown to be involved in
      fluoxetine metabolism in vitro and in vivo. CYP2C9 has also been shown to
      influence the metabolism of fluoxetine in vitro; however, this relationship has
      not been studied in humans. The aim of the present study was to evaluate the
      influence of CYP2D6 and CYP2C9 genotypes on the plasma concentration of
      fluoxetine and norfluoxetine in psychiatric patients during steady-state
      conditions. METHODS: White European psychiatric patients ( n=64) receiving
      antidepressant monotherapy with fluoxetine were studied. CYP2D6 and CYP2C9
      genotypes were determined by polymerase chain reaction-specific methods. The
      plasma concentrations of fluoxetine and its metabolite, norfluoxetine, were
      measured by high-performance liquid chromatography. RESULTS: The dose-corrected
      plasma concentrations of fluoxetine were related ( P<0.01, r=-0.36) to CYP2D6
      genotypes (number of active genes). The fluoxetine/norfluoxetine ratio also
      correlated ( P<0.01, r=-0.39) with the number of active CYP2D6 genes. Among
      patients with two CYP2D6 active genes, the dose-corrected plasma concentrations
      of fluoxetine and active moiety (fluoxetine plus norfluoxetine) were
      significantly ( P<0.05) higher in the CYP2C9*1/*2 and CYP2C9*1/*3 genotype groups
      than in CYP2C9*1/*1. However, dose-corrected (C/D) plasma concentrations of
      fluoxetine, active moiety and fluoxetine/norfluoxetine ratios were not highly
      different in the individuals with two mutated alleles as compared with those
      heterozygous for *2 or *3. CONCLUSION: The present results show that CYP2D6 and
      potentially CYP2C9 genotypes seem to influence fluoxetine plasma concentration
      during steady-state conditions in patients.

PMID- 14726988
TI  - Direction specific error patterns during continuous tracking of the subjective
      visual vertical.
AB  - The aim of this study was to characterize the error pattern of continuously
      tracking the perceived earth-vertical during roll rotations from upright to right
      or left ear-down and from right or left ear-down to upright. We compared the
      tracking responses of two paradigms, which either continuously activated the
      otoliths organs alone (constant velocity tilt) or both the otolith organs and the
      semicircular canals (constant acceleration tilt). The tracking responses of the
      subjective visual vertical showed characteristic differences depending on
      starting position and tilt direction relative to gravity. The error patterns in
      the constant-velocity and constant-acceleration tilt paradigm were reversed.
      Estimations during tracking, when otolith information was continuously changing,
      were more precise compared to estimations following fast tilts to fixed roll tilt
      positions. We conclude that the central processing underlying these perceptual
      tracking responses requires, besides the otolith input, information from the
      vertical semicircular canals.

PMID- 14726989
TI  - Eye position and memory saccade related responses in substantia nigra pars
      reticulata.
AB  - The substantia nigra pars reticulata (SNr), a major output nucleus of the basal
      ganglia, has been implicated anatomically, pharmacologically and physiologically
      in the generation of saccadic eye movements. However, the unique contribution of
      the SNr to saccade generation remains elusive. We studied the activity of SNr
      neurons while rhesus monkeys made saccades from different initial orbital
      positions, to determine what effects, if any, eye position had on SNr neuronal
      activity. We found that there was no effect of eye position on SNr neuronal
      responses. We also examined the responses of SNr neurons during memory-guided
      saccades to determine whether SNr discharges were affected by whether the target
      of the upcoming saccade was visible. We found that there was no change in
      response properties during memory saccade trials as compared to otherwise
      identical visually guided trials. SNr neurons appear to carry no information
      about either eye position or whether a movement is guided by a visible or
      remembered target. These results suggest that nigral signals are encoded in the
      same coordinate frame as those in the SC and FEF, but that unlike neuronal
      responses in these areas, SNr activity is not influenced by whether the saccade
      target remains visible until the movement is executed.

PMID- 14726991
TI  - [N-methyl-11C]Mirtazapine for positron emission tomography neuroimaging of
      antidepressant actions in humans.
AB  - RATIONALE: Many actions of antidepressant drugs cannot yet be studied using
      positron emission tomography (PET) neuroimaging due to lack of suitable
      radioligands. We believe that mirtazapine, radiolabeled with C-11, might be
      suitable for PET neuroimaging of alpha2-adrenoceptors in selected regions of the
      living human brain. OBJECTIVE: To determine the regional central biodistribution
      and pharmacokinetics of [N-methyl-11C]mirtazapine in humans. METHODS: Five
      healthy volunteers received an intravenous injection of [N-methyl-11C]mirtazapine
      for evaluating its metabolism, biodistribution and pharmacokinetics. RESULTS: [N
      methyl-11C]Mirtazapine entered the brain readily, with initial clearance from
      blood to tissue (K1) ranging from 0.31 ml/ml/min in amygdala to 0.54 ml/ml/min in
      thalamus. The rate of metabolism of [N-methyl-11C]mirtazapine in the bloodstream
      was relatively slow, with 20-40% of [11C]-derived radioactivity still present as
      parent compound at 60 min post-injection. The clearance of [N-methyl
      11C]mirtazapine from the tissue compartment (k2') ranged from a low of 0.03 min(
      1) in amygdala to a high of 0.06-0.07 min(-1) in thalamus and cerebellum. The
      volume of distribution (Ve') of [N-methyl-11C]mirtazapine was markedly greater in
      hippocampus and amygdala (11.3-12.0) than in cerebellum (6.7), with intermediate
      levels in the thalamus (9.4). CONCLUSIONS: [N-methyl-11C]Mirtazapine has suitable
      properties for PET neuroimaging. We envision [N-methyl-11C]mirtazapine as a
      molecular probe for PET imaging of antidepressant actions at sites such as alpha2
      adrenoceptors in the living human brain.

PMID- 14726992
TI  - Effects of persistent cocaine self-administration on amygdala-dependent and
      dorsal striatum-dependent learning in rats.
AB  - RATIONALE: The influence of persistent cocaine self-administration on learning
      and memory has never been evaluated. OBJECTIVES: Our objective was to isolate the
      effects of contingently administered cocaine from those of its general
      pharmacological or non-contingent actions on multiple memory system functioning.
      METHODS: A triad design was used to yoke passive cocaine and saline
      administration to the behavior of rats who were actively self-administering
      cocaine. Following 4 weeks of cocaine or saline exposure in 2-h sessions, six
      triads were tested in the amygdala-dependent conditioned cue preference task and
      dorsal striatum-dependent win-stay task in an eight-arm radial maze environment.
      Drug or saline sessions continued throughout task testing. RESULTS: Throughout
      task testing, rats actively and passively exposed to cocaine sustained a total
      daily intake of approximately 15 mg/kg. During the conditioned cue preference
      task, saline-exposed rats showed robust conditioned preference for a Froot Loops
      paired cue. Rats actively and passively exposed to cocaine showed no evidence of
      conditioning despite normal exploration in the maze during preference testing.
      For the win-stay task, no significant differences were found among the three
      groups in terms of the number of sessions to acquire the task or task accuracy at
      criterion. Rats actively or passively exposed to cocaine, however, completed
      sessions more quickly than saline-exposed rats at criterion. CONCLUSION: These
      findings suggest that contingent and non-contingent cocaine administration
      similarly disrupt stimulus-reward functions of the amygdala, but do not disrupt
      stimulus-response functions of the dorsal striatum. This dissociation may relate
      to differences in the rate by which dopamine is cleared from these tissues
      following cocaine exposure or possibly to cocaine-induced devaluation of natural
      rewards, which influences stimulus-reward learning, but not stimulus-response
      learning.

PMID- 14726994
TI  - Effects of acute and chronic clozapine on D-amphetamine-induced disruption of
      auditory gating in the rat.
AB  - RATIONALE: Auditory gating deficits observed in patients with schizophrenia have
      been modeled in animals administered the indirect-acting monoaminergic agonist, D
      amphetamine (AMPH). The atypical antipsychotic drug clozapine (CLOZ) reverses the
      disruption of auditory gating in schizophrenic patients. However, its effects on
      psychostimulant-induced deficits in animals have yet to be assessed. OBJECTIVES:
      In the present series of experiments, an auditory evoked potential paradigm was
      used to: (a) confirm the ability of AMPH to alter auditory gating in the
      anesthetized rat, (b) specify the nature of the accompanying change(s) in evoked
      potential waveforms and (c) determine the effects of CLOZ administration on AMPH
      induced alterations in auditory gating. METHODS: We compared the effects of acute
      (5 mg/kg, i.p.) and chronic (28 days, 0.5 mg/ml in drinking water) CLOZ on AMPH
      induced (1.8 mg/kg, i.p.) alterations in evoked potentials recorded in the
      hippocampus of anesthetized rats during presentation of a pair of identical
      tones. Gating was assessed by comparing the amplitude of conditioning and test
      responses in CLOZ and AMPH-treated rats. RESULTS: The ratio of test to
      conditioning response amplitude (T/C ratio) was not altered by vehicle or CLOZ
      alone. However, T/C ratio was significantly increased following AMPH due to
      suppression of the conditioning response. Acute but not chronic CLOZ attenuated
      but did not prevent the increase in T/C ratio. CONCLUSIONS: Qualitative
      differences between the idiopathic gating deficits observed in schizophrenic
      patients and AMPH-induced increases in T/C ratio in animals limit this models
      utility as a means of evaluating the ability of atypical antipsychotic drugs to
      restore normal sensory gating.

PMID- 14726993
TI  - Effect of the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the
      acute locomotor stimulant properties of cocaine, D-amphetamine, and the dopamine
      reuptake inhibitor GBR12909 in mice.
AB  - RATIONALE: Recent evidence suggests that, in addition to ascending monoaminergic
      systems, glutamate systems also play a role in psychostimulant-induced locomotor
      activity. The present study was conducted to examine the effects of the selective
      type-5 metabotropic glutamate receptor (mGluR5) antagonist 6-methyl-2
      (phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant effects of
      cocaine, D-amphetamine, and the dopamine reuptake inhibitor GBR12909. METHODS:
      Male DBA/2J mice were treated with saline or MPEP (1, 5, 20 or 30 mg/kg i.p.) 10
      min prior to the administration of cocaine (15 mg/kg or 30 mg/kg i.p.), D
      amphetamine (3 mg/kg or 5 mg/kg i.p.) or GBR12909 (10 mg/kg or 20 mg/kg i.p.).
      Locomotor activity was then monitored in an open-field environment for 30 min.
      The effects of MPEP alone (1, 5, 20 and 30 mg/kg i.p.) on locomotor activity were
      also examined. RESULTS: MPEP dose dependently inhibited the acute locomotor
      stimulant effects of cocaine, D-amphetamine, and the 10-mg/kg dose of GBR12909.
      However, MPEP had no effect on the locomotor stimulant effects of the higher (20
      mg/kg) dose of GBR12909. When tested alone, MPEP increased locomotor activity at
      doses of 5 mg/kg and 20 mg/kg. CONCLUSIONS: Our data suggest that mGluR5
      receptors not only mediate spontaneous locomotor activity in DBA/2J mice but also
      the acute locomotor stimulant effects of cocaine, D-amphetamine and lower doses
      of GBR12909. However, the fact that MPEP did not attenuate the locomotor
      stimulant effects of the high (20 mg/kg) dose of GBR12909 suggests complex
      interactions between metabotropic glutamate receptors, dopamine transporters and
      possibly other monoamines in the regulation of psychostimulant-induced locomotor
      activity.

PMID- 14726996
TI  - Effect of ambient temperature and a prior neurotoxic dose of 3,4
      methylenedioxymethamphetamine (MDMA) on the hyperthermic response of rats to a
      single or repeated ('binge' ingestion) low dose of MDMA.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) administration to
      rats produces acute hyperthermia and long-term neurotoxic damage to 5
      hydroxytryptamine (serotonin, 5-HT) neurones. OBJECTIVE: We wished to examine
      MDMA-induced hyperthermia in rats housed at normal (19 degrees C) and high (30
      degrees C) room temperatures and investigate the effect of a prior neurotoxic
      lesion. METHODS: Rectal temperature was measured after administration of single
      or repeated doses of MDMA to rats housed at 19 degrees C and 30 degrees C.
      RESULTS: MDMA (5 mg/kg i.p.) produced a sustained hyperthermic response in rats
      housed at 30 degrees C, but not in rats housed at 19 degrees C. A prior (5 weeks
      earlier) neurotoxic dose of MDMA (12.5 mg/kg i.p.) resulted in MDMA (5 mg/kg)
      producing a greater hyperthermic response in rats housed at 30 degrees C than in
      non-pre-treated animals. Repeated MDMA administration (binge dosing; 2, 4 or 6
      mg/kg x3) produced dose-dependent hyperthermia in rats housed at 19 degrees C,
      with MDMA (2 mg/kg x3) having little effect. However, this dose produced
      significant hyperthermia (> or =2 degrees C above control values)in rats housed
      at 30 degrees C following the third dose. A prior neurotoxic dose of MDMA
      resulted in MDMA (2 mg/kg x3) producing marked hyperthermia (>1 degrees C) after
      the first dose and severe hyperthermia (> or =2 degrees C) after the third dose.
      CONCLUSIONS: MDMA administration to rats housed at 30 degrees C produces a more
      severe hyperthermic response than that seen in rats housed at 19 degrees C. A
      prior neurotoxic dose enhances the response further in animals housed at 30
      degrees C. Binge dosing produces a higher final peak response than a similar non
      divided dose. This effect is more marked in animals housed at high room
      temperature. These data may have implications for recreational users of MDMA in
      hot environments, particularly those who may have damaged serotoninergic neurones
      because of prior heavy or frequent use of the drug.

PMID- 14726995
TI  - Effects of acute and chronic buspirone on impulsive choice and efflux of 5-HT and
      dopamine in hippocampus, nucleus accumbens and prefrontal cortex.
AB  - RATIONALE: Reduced central serotonin (5-HT) activity has been associated with
      impulsive choice behaviour, but there is no consensus about the precise nature of
      these effects. Behavioural and neurochemical effects of 5-HT(1A) agonists such as
      buspirone depend critically on the dose and the duration of treatment. We thus
      undertook a parametric study of the effects of acute and chronic buspirone on the
      performance on a test of delayed gratification, as well as on the efflux of
      serotonin and dopamine (DA) in cortical and subcortical regions in rats.
      OBJECTIVES: Three experiments examined (i) the effects of acute buspirone on
      impulsive choice and how such effects were modified by prior chronic exposure to
      buspirone; (ii) the effects of chronic buspirone on impulsive choice; (iii) the
      effects on impulsive choice of a selective 5-HT(1A) antagonist, WAY-100635 tested
      alone and in combination with buspirone; (iv) the effects of chronic and acute
      buspirone on 5-HT and DA efflux in anaesthetised rats. METHODS: In experiment 1,
      rats previously trained on the delayed gratification task were tested with acute
      buspirone (0.5, 1 and 2 mg/kg). The same rats were then treated with chronic
      buspirone (1 mg/kg/day) over the next 65 days, and the effects of acute buspirone
      (1 mg/kg) re-determined at 20, 45 and 65 days of chronic treatment. In experiment
      2, two groups of rats trained on the delayed gratification task were treated
      either with saline or buspirone (1 mg/kg/day) continually for 65 days before
      being tested with acute buspirone (1 mg/kg), WAY-100635 (0.08 mg/kg), or a
      combination of the two drugs. In experiment 3, rats received the same regimen of
      buspirone dosing as in experiment 2, before receiving in-vivo microdialysis for 5
      HT and DA in the ventral hippocampus, nucleus accumbens and medial prefrontal
      cortex. RESULTS: Acute buspirone dose dependently increased the choice for the
      small, immediate reinforcer (impulsive choice) but the effects of 1 mg/kg were
      reversed on chronic administration of buspirone. This increased choice of the
      large, delayed reinforcer, which was not accompanied by any changes in baseline
      (non-drugged) performance, was blocked by the 5-HT(1A) receptor antagonist WAY
      100635. The chronic buspirone regimen did not alter buspirone-evoked reductions
      in 5-HT efflux in hippocampus but did lead to a differential effect of acute
      buspirone in medial prefrontal cortex, with the chronic buspirone and saline
      groups exhibiting decreases and increases in efflux, respectively. There were no
      systematic changes in DA efflux under any condition. CONCLUSIONS: These findings
      show that the effects of acute buspirone on impulsive choice are reversed
      following chronic treatment and are mediated by 5-HT(1A) receptors, and suggest,
      in addition, that the behavioural effects may involve changes in 5-HT functioning
      in medial prefrontal cortex.

PMID- 14726997
TI  - Mood disorders and serotonin transporter density in ecstasy users--the influence
      of long-term abstention, dose, and gender.
AB  - RATIONALE: Neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA,
      "ecstasy") on the serotonin (5-HT) system have been described in animals and
      humans, but little is known about long-term effects of ecstasy use on mood.
      OBJECTIVES: To investigate short-term and long-term effects of ecstasy use on
      mood and its association with 5-HT neurotoxicity, dose, and gender in humans.
      METHODS: Fifteen moderate ecstasy users, 23 heavy ecstasy users, 16 former heavy
      ecstasy users and 15 drug-using, but ecstasy-naive controls were included. Mood
      was assessed using the Composite International Diagnostic Interview (CIDI) and
      the Beck Depression Inventory (BDI). Outcomes were correlated with 5-HT
      transporter (SERT) density, assessed with [123I]beta-CIT single photon emission
      computed tomography (SPECT). RESULTS: The prevalence of mood disorders assessed
      by CIDI did not differ between all groups. The overall test for differences in
      BDI scores between groups was near significance (P=0.056), with BDI scores higher
      in former heavy ecstasy users than in ecstasy-naive controls (P=0.045). BDI
      scores were correlated with the total number of ecstasy tablets used (r=0.310;
      P=0.021). No associations between CIDI or BDI outcomes and SERT density or gender
      were observed. CONCLUSIONS: These results suggest that ecstasy use is not
      associated with clinical depression (CIDI). However, the number of ecstasy
      tablets taken lifetime was associated with higher BDI scores for depressive mood,
      and this relationship seemed to persist after ecstasy use had stopped. We did not
      find that depressed mood in ecstasy users was associated with decrease in SERT
      density. Prospective studies are needed to establish the causal relationship
      between ecstasy use and depressed mood.

PMID- 14726998
TI  - Selective processing of food words during insulin-induced hypoglycemia in healthy
      humans.
AB  - RATIONALE: Hypoglycemia leads to undernutrition of the brain. Favoring selective
      processing of food stimuli would be an adaptive cognitive strategy. However,
      hypoglycemia is known to impair several aspects of cognitive function, and it is
      unknown whether selective cognitive processing of food stimuli occurs during
      insulin-induced hypoglycemia. METHODS: In a single-blind repeated measures
      design, healthy young adults (n=12, six female, mean age 28 years; mean body mass
      index 22.5 kg/m(2)) performed a standard Stroop word-color test, as well as a
      variant with food words designed to detect selective processing of food cues. Two
      sessions were scheduled with a 4-week interval. In each session, a
      hyperinsulinemic clamp method produced a normoglycemic (plasma glucose: 4.7
      mmol/l) period, followed on 1 day by a hypoglycemic (2.7 mmol/l) testing period,
      and on the other day a second normoglycemic testing period (counterbalanced
      order). RESULTS: Color naming verbal reaction time (RT) increased during
      hypoglycemia (P<0.0001). The extent of the Stroop cognitive interference was
      independent of plasma glucose level. The key finding is that RT for food words
      increased more than for non-food control words (P<0.004), and this effect was not
      predicted by hunger ratings. CONCLUSIONS: Our data provide new evidence that
      during hypoglycemia, attention is directed selectively to food-relevant stimuli.
      The results are discussed in terms of adaptation.

PMID- 14726999
TI  - Lack of startle modulation by smoking cues in smokers.
AB  - RATIONALE: The startle reflex methodology has been used to study the effects of
      nicotine in humans and the motivational effects of smoking cues in smokers.
      However, no other studies investigate startle modulation by smoking cues in
      smokers compared to non-smokers. In the other studies, smoking deprivation was
      manipulated in smokers or smokers were not compared directly to non-smokers.
      OBJECTIVE: The goal of this study was to examine the temporal course of
      information processing following the presentation of a smoking-related cue using
      the startle probe methodology in smokers compared to non-smokers. METHODS: Thirty
      four smokers were selected on the basis of nicotinic dependence according to the
      DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral
      pictures and smoking related pictures displayed on a computer screen. Acoustic
      startle stimuli were delivered at various times after picture onset (60, 120 or
      5000 ms) to examine inhibition by lead stimulus and the affective modulation of
      startle. RESULTS: The magnitude of startle reflex inhibition increased in smokers
      compared to non-smokers, at 60 and 120 ms. In all, there was no PicturexGroup
      interaction effect. CONCLUSION: We showed that smoking cues have no impact on the
      startle reflex of either group, even if, in line with previous results, prepulse
      inhibition was higher in smokers than non-smokers. These results suggest that
      smoking cues have no effect on the positive reinforcement of nicotine
      consumption, and that cognitive factors play a primary role in the development
      and maintenance of tobacco dependence.

PMID- 14727000
TI  - Influence of fluoxetine on positive and negative affect in a clinic-based smoking
      cessation trial.
AB  - RATIONALE: Fluoxetine improves affect in clinical syndromes such as depression
      and premenstrual dysphoric disorder. Little is known about fluoxetine's influence
      on mood changes after quitting smoking, which often resemble sub-clinical
      depression. OBJECTIVES: The present study, a re-analysis of previously published
      data (Niaura et al. 2002), examined fluoxetine's effect on changes in negative
      and positive affect following quitting smoking. METHODS: Adult smokers (n=175)
      without clinically significant depression were randomized on a double-blind basis
      to receive fluoxetine hydrochloride (30 or 60 mg daily) or placebo for 10 weeks
      in combination with cognitive-behavioral therapy (CBT) for smoking cessation. We
      postulated that fluoxetine would beneficially influence post-cessation changes in
      positive and negative affect. RESULTS: Mood change across treatment was analyzed
      using mixed linear modeling controlling for initial level of nicotine dependence,
      plasma fluoxetine metabolites, and change in cotinine (a nicotine metabolite) at
      each visit. Relative to placebo, those on 60 mg fluoxetine experienced an
      elevation in positive affect that increased across time [t(526)=2.50, P=0.01],
      and a reduction in negative affect that returned to baseline across time
      [t(524)=2.26, P=0.02]. There were no differences between 30 mg and placebo on
      changes in positive or negative affect. CONCLUSIONS: Results indicate that 60 mg
      of fluoxetine improves both positive and negative mood states after quitting
      smoking and that diminished positive affect may be an overlooked affective
      response to smoking cessation.

PMID- 14727001
TI  - Repeated nicotine exposure enhances responding with conditioned reinforcement.
AB  - RATIONALE: Stimuli associated with a reinforcer (e.g., an addictive drug) can
      acquire conditioned reinforcing effects. Clinical observations indicate that
      smoking depends strongly upon conditioned reinforcement (i.e., cues support
      smoking behavior); however, little is known about the effects of repeated
      nicotine exposure on these processes. OBJECTIVE: This study investigated the
      consequences of prior repeated nicotine exposure on responding with conditioned
      reinforcement and on the potentiation of conditioned reinforcement by intra-NAc
      amphetamine infusion. METHODS: Rats received repeated saline or nicotine
      injections (0.35 mg/kg; 15 days) and were, following 3 days of withdrawal,
      trained to associate a tone + light stimulus with water reinforcement for 10
      days. Animals were subsequently tested on acquisition of a new instrumental
      response with conditioned reinforcement (i.e., 14 days after the final nicotine
      injection). In additional experiments, animals received an infusion of
      amphetamine (10 microg per side) prior to the conditioned reinforcement test.
      RESULTS: Prior repeated nicotine exposure produced a behaviorally specific
      enhancement of responding with conditioned reinforcement. Furthermore, repeated
      nicotine pretreatment also augmented the potentiation of conditioned
      reinforcement by intra-NAc amphetamine. CONCLUSIONS: These findings demonstrate
      that prior repeated nicotine exposure augments the control over behavior by a
      conditioned reinforcer. Such long-lasting alterations in incentive motivational
      processes produced by repeated nicotine exposure may depend on drug-induced
      neuroadaptations in dopamine-regulated signaling within limbic-striatal brain
      regions that could underly persistent and compulsive aspects of addiction.

PMID- 14727002
TI  - Effects of kappa-opioid receptor ligands on intracranial self-stimulation in
      rats.
AB  - RATIONALE: Elevations in cAMP response element binding protein (CREB) function
      within the mesolimbic system of rats reduce cocaine reward in place conditioning
      studies and increase immobility in the forced swim test. Each of these behavioral
      adaptations can be interpreted as a depressive-like effect (i.e., anhedonia,
      despair) that may reflect reduced activity of brain reward systems. Furthermore,
      each effect appears due to increases in CREB-mediated expression of dynorphin,
      since each is attenuated by intracranial injections of the kappa-opioid receptor
      antagonist norBNI. OBJECTIVES: Intracranial self-stimulation (ICSS) studies were
      conducted in rats to determine whether administration of a kappa-agonist would
      have depressive-like effects on brain stimulation reward, and whether
      pretreatment with a kappa-antagonist would attenuate any such effects. Conditions
      that have depressive effects in people (e.g., drug withdrawal) increase the
      threshold amounts of stimulation required to sustain ICSS in rats. METHODS:
      Sprague-Dawley rats with lateral hypothalamic stimulating electrodes were tested
      in a "curve-shift" variant of the ICSS procedure after systemic administration of
      the kappa-agonist U-69593 alone, the novel kappa-antagonist 5'
      acetamidinoethylnaltrindole (ANTI) alone, or co-administration of both drugs.
      RESULTS: U-69593 dose dependently increased ICSS thresholds, suggesting that
      activation of kappa-receptors reduced the rewarding impact of the brain
      stimulation. ANTI had no effects on its own, but it attenuated increases in ICSS
      thresholds caused by the agonist. CONCLUSIONS: These data provide further
      evidence that stimulation of brain kappa-receptors may trigger certain depressive
      like signs, and that kappa antagonists may have efficacy as antidepressants
      without having reward-related actions of their own.

PMID- 14727003
TI  - AR-R 17779 improves social recognition in rats by activation of nicotinic alpha7
      receptors.
AB  - RATIONALE: Nicotine and agonists at alpha(4)beta(2) and alpha(7) nicotinic
      acetylcholine receptors (nAChRs) improve learning and memory. The alpha(7)-nAChR
      subtype is of special interest, since it appears to play no role in the abuse
      liability of nicotine. OBJECTIVES AND METHODS: To further investigate the role of
      the alpha(7)-nAChR in learning and memory, the effects of the specific alpha(7)
      nAChR agonist AR-R17779 on cognition were measured in the rat social recognition
      test (SRT) and the effect of the alpha(7)-nAChR antagonist methyllycaconitine
      (MLA) was studied. The SRT and a scopolamine-induced deficit version were
      validated with the acetylcholinesterase inhibitor metrifonate. Social memory was
      measured by the ability of an adult rat to recognize a juvenile rat after a
      delay. The difference in social interaction time (SIT) was measured between two
      encounters. The difference in SIT is expressed as percent reduction in social
      interaction time (%RSIT). RESULTS: Metrifonate (10 and 30 mg/kg PO) increased
      %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed
      the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR
      R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing
      a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and
      1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg
      SC) in unimpaired animals were reversed by MLA (10 micro g ICV), which induced a
      decrease of %RSI at a 15-min retention interval when given alone. CONCLUSIONS: AR
      R17779 increased social recognition memory by activation of alpha(7)-nAChRs,
      suggesting that alpha(7)-nAChR agonists possess cognitive-enhancing properties.

PMID- 14727004
TI  - Ketamine impairs response inhibition and is positively reinforcing in healthy
      volunteers: a dose-response study.
AB  - RATIONALE: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that
      has medical indications but is also used as a recreational drug. Previous
      research has found persisting cognitive and psychotogenic effects of ketamine in
      chronic abusers of this drug 3 days after an acute dose. OBJECTIVE: The present
      study aimed to investigate the effects of ketamine on two processes related to
      drug abuse, response inhibition and reinforcement, and to examine whether an
      acute dose of ketamine produced residual cognitive effects in healthy volunteers.
      METHODS: Fifty-four healthy volunteers were given an 80-min infusion of one of
      two doses (0.4, 0.8 mg kg(-1)) of ketamine or placebo. Subjects completed a
      battery of tests at three time points: pre-infusion, during the infusion and 3
      days later at follow-up. The battery consisted of tests of episodic and semantic
      memory, schizophrenic-like and dissociative symptoms, response inhibition and
      measures of subjective effects, including mood, bodily symptoms and enjoyment of
      and desire for the drug. RESULTS: Ketamine acutely impaired response inhibition
      and had related biphasic effects on the subjective reinforcing effects of the
      drug. Ketamine also acutely impaired episodic but not semantic memory and
      increased schizophrenic-like and dissociative symptoms. No residual cognitive
      effects were observed 3 days following an acute dose. CONCLUSIONS: The lack of
      residual effects in healthy volunteers on day 3 indicates that impairments found
      on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be
      related to its capacity both to reinforce and to decrease response inhibition.

PMID- 14727005
TI  - Airway hyperresponsiveness to bradykinin induced by allergen challenge in
      actively sensitised Brown Norway rats.
AB  - The mechanism(s) of bradykinin-induced bronchoconstriction was investigated in
      the Brown Norway (BN) rat model of allergic asthma. Bronchoconstrictor responses
      to i.v. bradykinin in BN rats were maximally augmented 24 h following challenge
      with allergen and declined at later time points. Histological evaluation of the
      inflammatory status of the lungs after ovalbumin (OA) challenge showed a marked
      inflammatory response, which was maximal at 24 h and declined thereafter.
      However, pretreatment with budesonide did not inhibit the augmented
      bronchoconstrictor response to bradykinin 24 h after allergen challenge. The
      selective B1 receptor agonist, Lys-[desArg9]-BK had no bronchoconstrictor
      effects, whereas the selective B2 receptor antagonist, HOE 140, abolished the
      response to bradykinin in OA-challenged animals. The augmented response to
      bradykinin was not affected by methysergide, indomethacin, disodium cromoglycate,
      iralukast, the 5-lipoxygenase inhibitor, CGS8515, or the NK2 receptor antagonist,
      SR48968. It was, however, partially inhibited by atropine both in saline- and OA
      challenged animals. Pretreatment with captopril and thiorphan markedly
      potentiated responses to bradykinin both in saline- and OA-challenged animals.
      Thus, augmentation of the bronchoconstrictor response to bradykinin occurs in
      actively sensitised BN rats 24 h after challenge with OA and is associated with
      marked pulmonary inflammation. The response is entirely B2 receptor mediated and
      approximately 50% of the response is cholinergic. However, mast cell activation,
      the products of the cyclooxygenase or 5-lipoxygenase pathways and tachykinins are
      not involved. Peptidase inhibition mimics the effect of allergen challenge on the
      bronchoconstrictor response to bradykinin and it remains possible that the
      mechanism of the augmented response to bradykinin following allergen challenge
      involves downregulation of peptidase activity as a consequence of the
      inflammatory response.

PMID- 14727006
TI  - Involvement of alpha1 and beta-adrenoceptors in adrenaline stimulation of the
      glucagon-secreting mouse alpha-cell.
AB  - Stimulation of glucagon release and inhibition of insulin secretion from the
      islets of Langerhans are important for the blood-glucose-elevating effect of
      adrenaline. The mechanisms by which adrenaline accomplishes these actions may
      involve direct effects and indirect ones mediated by altered release of other
      islet hormones. In the present study we investigated how adrenaline affects the
      cytoplasmic Ca2+ concentration, which controls glucagon secretion from the
      pancreatic alpha-cell. The studies were performed on isolated mouse alpha-cells,
      which were identified by immunocytochemistry. The adrenaline effects consisted of
      initial mobilisation of intracellular Ca2+, accompanied by voltage-dependent
      influx of the ion. Part of the effect could be attributed to beta-adrenoceptor
      activation, as it was mimicked by the rise in cAMP and inhibited by the
      antagonist propranolol as well as the protein kinase A inhibitor adenosine 3',5'
      cyclic monophosphorothioate Rp-isomer. alpha1-Adrenoceptors were also involved,
      since the antagonists phentolamine and prazosin completely abolished the effects
      of adrenaline. Experiments with clonidine and yohimbine gave little evidence of a
      role of alpha2-adrenoceptors. The results indicate that alpha1- and beta
      adrenoceptors on the alpha-cells mediate adrenaline-stimulated glucagon
      secretion. The complete inhibition of the adrenaline response after blocking
      alpha1-adrenoceptors indicates an interaction with the beta-adrenergic pathway.

PMID- 14727008
TI  - Chorismate mutase of Thermus thermophilus is a monofunctional AroH class enzyme
      inhibited by tyrosine.
AB  - aroG, encoding the monofunctional chorismate mutase (TtCM) of the thermophilic
      gram-negative bacterium Thermus thermophilus, was cloned and its gene product
      characterized. TtCM was purified to homogeneity on an SDS polyacrylamide gel as a
      His-fusion protein with a deduced molecular mass of 15.8 kDa. The enzyme belongs
      to the rare group of AroH-type chorismate mutases which are mainly found in gram
      positive bacteria of the Bacillus/ Clostridia group and have recently also been
      described for gram-negative organisms. The native molecular mass is consistent
      with a pseudo-alpha/beta barrel enzyme that is organized as a trimer. Comparison
      of the enzyme's structure with that of its mesophilic counterpart from Bacillus
      revealed an increase in hydrophilicity on the protein's surface, greater
      hydrophobicity in cavities within the protein, and greater restriction of
      conformational freedom, features that contribute to the thermal stability of this
      chorismate mutase. The kinetic data show Michaelis-Menten substrate saturation
      with a Km of 290 microM, and a kcat/ Km value of 180 s(-1) mM(-1). TtCM was
      inhibited by tyrosine with a Ki =34 microM, possibly in a competitive manner.

PMID- 14727007
TI  - Agmatine (decarboxylated arginine), a modulator of liver cell homeostasis and
      proliferation.
AB  - Agmatine interferes with polyamine metabolism and cell growth in cell culture.
      When absorbed from the gastrointestinal tract, it is accumulated in the liver.
      Based on these facts, the aim of the present study was to investigate the effects
      of agmatine on the proliferation of rat and human hepatoma cells and on
      regeneration of rat liver after partial two-thirds hepatectomy. In cultured cells
      of the rat and human hepatoma cell lines McRH7777 and HepG2 respectively,
      agmatine reduced ATP and protein contents (50% inhibition in the range of 169-569
      microM) which were determined as estimates for the cell number. This
      antiproliferative action was not due to an effect on ornithine decarboxylase
      antizyme, since its intracellular concentration was not significantly changed by
      agmatine. In addition, agmatine metabolism by diamine oxidase seems not to be
      involved in the inhibition of cell growth and proliferation because the diamine
      oxidase inhibitor aminoguanidine did not alter agmatine's antiproliferative
      action. After two-thirds hepatectomy, daily administration of 250 mg and 500 mg
      agmatine to rats for 6 days by gavage reduced the weight gain of the remnant
      liver on day 7 by 19.5+/-0.9% and 22.3+/-1.5% respectively. The decrease in
      regeneration correlated with a pronounced accumulation of agmatine in the liver.
      Hence, the present data provide evidence of an involvement of agmatine in liver
      cell growth.

PMID- 14727009
TI  - Awareness of osteoporosis among physicians in China.
AB  - Epidemiological studies have projected a vast increase in osteoporotic fractures
      in Asia, with the majority occurring in China. Awareness of osteoporosis among
      medical professionals and the pattern of management in Asia have not been
      explored. A total of 504 doctors in Hong Kong, China with their self-reported
      practice likely to receive clients with or at risk of osteoporosis were invited
      to complete a postal questionnaire on the diagnosis and management of their
      osteoporotic patients. In all, 204 questionnaires were returned, with a response
      rate of 41%. Only 76% of the respondents reported treating osteoporosis patients
      in their practice. Ninety-one percent believed that osteoporosis was under
      diagnosed. The asymptomatic nature of the disease (66%), inaccessibility (45%)
      and high cost (54%) of the diagnostic tools were considered major reasons for
      under-diagnosis. DXA was employed for diagnosis by only 53% of the doctors.
      Peripheral machines such as ultrasound and quantitative computed tomography were
      used by 35% of the responders as the only diagnostic tool, especially among
      clinic-based doctors (clinic-based physicians 47%, hospital-based physicians 17%;
      P<0.001). Thirty-three percent of the surveyed doctors were unaware of published
      guidelines for bone mineral density (BMD) measurements. Concerning treatment
      goals, 82% considered prevention of future fractures and 66% believed improvement
      in the quality of life of patients as critical or highly important, whereas only
      about half of the doctors thought that increase in BMD was important. On the
      other hand, 60% of the doctors considered the cost of therapy a critical or
      highly important element in the management of osteoporosis. This study showed
      that physicians in Hong Kong were aware of osteoporosis, though the disease was
      still under-diagnosed due to inaccessibility and high cost of the diagnostic
      tools and therapeutic agents. These findings stress the importance of expanding
      efforts to increase knowledge and awareness among health care providers and also
      provide future directions for developing strategies for managing osteoporosis in
      developing Asian regions.

PMID- 14727010
TI  - Restoration of euthyroidism accelerates bone turnover in patients with
      subclinical hypothyroidism: a randomized controlled trial.
AB  - This study evaluated the effect of physiological l-thyroxine (L-T4) treatment on
      bone metabolism in patients with subclinical hypothyroidism. Sixty-six women with
      subclinical hypothyroidism (TSH 11.7 +/- 0.8 mIU/l) were randomly assigned to
      receive L-T4 or placebo for 48 weeks. Sixty-one of 66 patients completed the
      study. Individual L-T4 replacement (mean dosage 85.5 +/- 4.3 microg/day) was
      performed targeting euthyroid thyroid-stimulating hormone (TSH) levels. The
      primary outcome measure was 24- and 48-week change in markers of bone formation
      (total and bone alkaline phosphatase [ALP, bone ALP], osteocalcin [OC]) and
      resorption (pyridinoline [PYD] and deoxypyridinoline [DPD], C-terminal cross
      linking telopeptide type I [CTX]). Secondary outcomes were 48-week changes in
      bone mineral density (BMD) of the lumbar spine and hip, measured by dual-energy X
      ray absorptiometry. Compared with placebo, l-thyroxine ( n=31) resulted in
      significant activation of bone turnover. Overall, a significant treatment effect
      was observed for DPD (between-group difference 16.0%; 95%CI, 10.9 to 21.1), CTX
      (29.9%; 95%CI, 23.3 to 36.5), and bone ALP (13.2%; 95%CI, 6.6 to 19.7) after 24
      weeks. At the end of the study, lumbar BMD in the both treatment groups differed
      by 1.3% (95%CI, -2.9 to 0.5) with lower levels in l-thyroxine treated women.
      Significant difference in BMD between groups was also observed at the trochanter.
      We conclude that physiological l-thyroxine treatment accelerates bone turnover
      reflecting early activation of bone remodeling units in the initial replacement
      of subclinical hypothyroidism. The observed bone loss could be interpreted as an
      adaptive mechanism on decreased bone turnover in preexistent hypothyroidism, and
      not as l-thyroxine-induced clinically important bone loss. However, long-term
      studies are needed to confirm this assumption.

PMID- 14727011
TI  - Histomorphometric evaluation of daily and intermittent oral ibandronate in women
      with postmenopausal osteoporosis: results from the BONE study.
AB  - The bisphosphonate ibandronate, administered either daily or intermittently with
      an extended between-dose interval of >2 months, has been shown to reduce
      significantly the incidence of vertebral fractures, to increase bone mineral
      density and to reduce levels of biochemical markers of bone turnover in a phase
      III randomized study in women with postmenopausal osteoporosis (PMO). Bone
      histomorphometry was performed on a subgroup of women participating in this study
      in order to assess bone quality and architecture. The patients were randomized to
      receive one of the following: placebo, continuous oral daily ibandronate (2.5
      mg/day) or intermittent oral ibandronate (20 mg every other day for 12 doses
      every 3 months). Out of the overall study population of 2,946 patients, 110 were
      randomly assigned to undergo transiliac bone biopsy at either month 22 or month
      34 of treatment. The primary safety endpoint was osteoid thickness in trabecular
      bone, which was measured to exclude treatment-induced bone mineralization
      defects. Secondary safety endpoints assessed bone volume, bone turnover and micro
      architecture. The primary efficacy endpoint was bone mineralizing surface. In all
      bone biopsy cores, newly formed trabecular bone retained its structure without
      any signs of woven bone. Marrow fibrosis and signs of cellular toxicity were not
      observed. Quantitative assessment demonstrated no impairment in mineralization of
      bone matrix: osteoid thickness tended to be similar or slightly lower in the
      ibandronate groups versus the placebo group. All secondary safety variables and
      the bone efficacy parameter were consistent with the production of normal
      quality, newly formed bone and a modest reduction in bone turnover with both
      ibandronate regimens relative to placebo. Long-term treatment with oral
      ibandronate, even when administered with an extended between-dose interval of >2
      months, produces normal-quality, newly formed bone in women with PMO.

PMID- 14727012
TI  - Calcaneal ultrasound predicts early postmenopausal fractures as well as axial
      BMD. A prospective study of 422 women.
AB  - Low calcaneal ultrasound measurement (quantitative ultrasound, QUS) has been
      shown to predict fractures in elderly women. However, only a few studies have
      examined its ability to predict perimenopausal and early postmenopausal
      fractures. We conducted a prospective population-based cohort study to assess the
      capability of QUS as compared to axial BMD measurement to predict early
      postmenopausal fractures at that age. Four hundred and twenty-two women (mean age
      59.6, range 53.7-65.3) from the Kuopio Osteoporosis Risk Factor and Prevention
      Study (OSTPRE) were randomly chosen to undergo a calcaneal ultrasound
      measurement. In all, 9.4% of these women were premenopausal at the time of
      measurement. Thirty-two follow-up fractures were reported during the mean follow
      up of 2.6 years (SD 0.7). These were validated with patient record perusal.
      Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index
      (SI) were significantly lower among women with than without fracture ( P-values
      0.028, 0.001 and 0.001, respectively). Mean T-score adapted from SI was -1.5 (95%
      CI -1.7 to -1.2) for fracture group and -1.0 (95% CI -1.1 to -0.9) for the non
      fracture group. All QUS measurements predicted fractures even after adjusting for
      age, weight, height, previous fracture history, femoral neck BMD and use of
      hormone replacement therapy according to Cox regression. The adjusted hazard
      ratios (HR, 95% confidence interval) of a follow-up fracture for a 1 SD decrease
      were 1.80 (1.27-2.56), 1.72 (1.21-2.45) and 1.43 (1.01-2.03) for SOS, SI and BUA,
      respectively. Similarly, the adjusted HR for a 1 SD decrease of spinal BMD was
      1.27 (0.85-1.94) and for that of femoral neck BMD 1.14 (0.78-1.70). In receiver
      operator analyses, the area under the curve (AUC) was greatest for QUS
      measurements: SOS (AUC=0.68), stiffness (AUC=0.67), BUA (AUC=0.62) and least for
      lumbar BMD (AUC=0.56), while and femoral neck BMD (AUC=0.59). The difference
      between AUCs was statistically significant between SI and lumbar BMD ( P=0.02,
      Duncan's P=0.07). We conclude that low calcaneal QUS predicts early
      postmenopausal fractures as well as or even better than axial BMD.

PMID- 14727013
TI  - Relationship between body composition and bone mineral density in healthy young
      and premenopausal Chinese women.
AB  - This study investigated the relative contribution of fat mass and lean mass to
      bone mineral density (BMD) in young and premenopausal healthy Chinese women. The
      study was performed in 282 young and premenopausal healthy women with regular
      menstrual cycles. The BMD at lumbar spine (L2-L4), total hip and total body,
      together with fat mass and lean mass were assessed by dual-energy X-ray
      absorptiometry (DXA); body height, weight, waist and hip circumference were also
      measured, and body mass index (BMI) and waist-hip ratio were calculated. Fat mass
      was a major determinant for BMI, BMI and lean mass were positively related to L2
      L4, total hip and total body bone density ( P<0.001 for all), lean mass was the
      only independent factor contributing to BMD at L2-L4 (standardized coefficient
      beta=0.282, P<0.001), total hip (beta=0.336, P<0.001) and total body (beta=0.361,
      P<0.001) in multiple stepwise regression analysis. The correlation between BMI
      and BMD was improved after adjustment for fat mass, while decreased or even lost
      when lean mass was adjusted. These data suggested that in the Chinese population,
      lean mass is an important factor determining BMD in young and premenopausal
      women.

PMID- 14727014
TI  - Evidence for an association of methylene tetrahydrofolate reductase polymorphism
      C677T and an increased risk of fractures: results from a population-based Danish
      twin study.
AB  - Osteoporotic fractures are some of the major causes of morbidity and health care
      expenditure among the elderly. Identifying subjects at risk could be of major
      importance since several preventive treatments are now available. A large genetic
      component in the development of osteoporosis has been established. Previous
      studies concerning association of the common point mutation C677T in
      methylentetrahydrofolate reductase (MTHFR) and osteoporosis have revealed
      contradictory results. The aim of this study was to test the association between
      the MTHFR polymorphism, homocysteine, and fractures in a population-based sample
      of Danish twins aged 73+. In total, 689 subjects, with a mean age of 78 years,
      participated. Genotype and data of fractures are available from 687 subjects--144
      with a previously diagnosed fracture. The genotype distribution is as follows:
      CC, CT, and TT genotypes, 317 (46.1%), 298 (43.3%), and 73 (10.6%), respectively.
      Using the proportional odds-ratio model adjusted for age, gender, and body mass
      Index, the odds-ratio of fracture was 1.5 per number of T alleles--meaning that
      fracture risk is 1.5 times higher in the CT group compared with the CC group and
      again 1.5 times higher in the TT group compared with the CT group. Homocysteine,
      smoking, and self-reported hormone use provided no significant contribution to
      fracture risk. Using biometrical modelling, the heritability of the liability to
      fractures was found to be approximately 0.10, when the effect of the MTHFR locus
      was included, and 0.07 when it was omitted. But both confidence intervals include
      zero and the estimates are therefore not significant. In conclusion, we here
      provide evidence for a significant impact of the MTHFR genotype on the occurrence
      of fractures in an elderly Danish population.

PMID- 14727015
TI  - Prediction of mortality in an Indian intensive care unit. Comparison between
      APACHE II and artificial neural networks.
AB  - OBJECTIVE: To compare hospital outcome prediction using an artificial neural
      network model, built on an Indian data set, with the APACHE II (Acute Physiology
      and Chronic Health Evaluation II) logistic regression model. DESIGN: Analysis of
      a database containing prospectively collected data. SETTING: Medical-neurological
      ICU of a university hospital in Mumbai, India. SUBJECTS: Two thousand sixty-two
      consecutive admissions between 1996 and 1998. INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: The 22 variables used to obtain day-1 APACHE II score and risk of
      death were recorded. Data from 1,962 patients were used to train the neural
      network using a back-propagation algorithm. Data from the remaining 1,000
      patients were used for testing this model and comparing it with APACHE II. There
      were 337 deaths in these 1,000 patients; APACHE II predicted 246 deaths while the
      neural network predicted 336 deaths. Calibration, assessed by the Hosmer-Lemeshow
      statistic, was better with the neural network (H=22.4) than with APACHE II
      (H=123.5) and so was discrimination (area under receiver operating characteristic
      curve =0.87 versus 0.77, p=0.002). Analysis of information gain due to each of
      the 22 variables revealed that the neural network could predict outcome using
      only 15 variables. A new model using these 15 variables predicted 335 deaths, had
      calibration (H=27.7) and discrimination (area under receiver operating
      characteristic curve =0.88) which was comparable to the 22-variable model
      (p=0.87) and superior to the APACHE II equation (p<0.001). CONCLUSION: Artificial
      neural networks, trained on Indian patient data, used fewer variables and yet
      outperformed the APACHE II system in predicting hospital outcome.

PMID- 14727016
TI  - Blood polymorphonuclear leukocyte migration as a predictive marker for infections
      in severe trauma: comparison with various inflammation parameters.
AB  - OBJECTIVE: To assess in patients with multiple trauma the relevance of the
      following as predictive markers for infections: the inflammation parameters white
      blood count, body temperature, blood polymorphonuclear leukocyte (PMN) migration;
      blood levels of C-reactive protein, PMN elastase, procalcitonin, neopterin,
      interleukin 6, interleukin 8, malondialdehyde, total antioxidative status; the
      stress parameters cortisol and lactate. DESIGN: Prospective observational cohort
      study. SETTING: Intensive Care Unit of a university surgical department.
      PATIENTS: Twenty-six patients with multiple trauma of differing severity.
      MEASUREMENTS AND RESULTS: Trauma severity was estimated by the ISS. PMN migration
      upon F-Met-Leu-Phe stimulation was determined in fresh whole blood in a ready-for
      use, one-way membrane filter assay and evaluated by automated image analysis. The
      other parameters were measured with commercially available tests. During
      hospitalization, nine patients developed infections, and 17 patients were free of
      infection. PMN migration below a critical minimum preceded infections in eight of
      the infected, but occurred in only three of the non-infected patients
      (positive/negative predictive values 0.72/0.93; sensitivity/specificity
      0.88/0.82; likelihood ratio 5.0). Fever (> or =38.0 degrees C) had predictive
      values of 0.83/0.80 and a high likelihood ratio of 9.4, but a low
      sensitivity/specificity of 0.55/0.94. The other parameters were without
      significance. Procalcitonin, elastase, C-reactive protein, neopterin and lactate
      correlated positively with the injury severity score. CONCLUSION: PMN migration
      proved to be a highly sensitive predictive marker for infections. The whole-blood
      PMN migration test may facilitate early aggressive antimicrobial therapy.

PMID- 14727017
TI  - Transport of critically ill children in a resource-limited setting: alternatives
      to a specialized retrieval team.

PMID- 14727018
TI  - The effect of back-up rate during non-invasive ventilation in young patients with
      cystic fibrosis.
AB  - OBJECTIVE: The aim of the study was to evaluate the effect of the back-up rate on
      respiratory effort during non-invasive mechanical ventilation. DESIGN: An in
      vitro study evaluated the inspiratory trigger in seven domiciliary ventilators.
      Then, a prospective, randomized, crossover trial compared the effect on
      respiratory effort of three different back-up rates during pressure support (PS)
      and assist-control/volume-targeted (AC/VT) ventilation. SETTING: A research unit
      and a tertiary referral pediatric center. PATIENTS: Ten patients with cystic
      fibrosis (CF). INTERVENTIONS: During the in vivo study, the back-up rate was
      progressively increased to the maximum that patients could tolerate (Fmax) and
      respiratory effort, as judged by pressure/time product of the diaphragm
      (PTPdi/min), was compared between the two ventilatory modes. RESULTS: Differences
      were observed between trigger pressure, trigger time delay, trigger pressure/time
      product and the slope between flow and pressure in the seven ventilators. PS and
      AC/VT ventilation were associated with a decrease in respiratory effort
      (PTPdi/min was 518+/-172, 271+/-119 and 291+/-138 cmH(2)O. s(-1). min(-1), for
      spontaneous breathing, PS and AC/VT ventilation, respectively, p=0.05). During
      the two modes, increasing the back-up rate to Fmax resulted in a greater
      reduction in PTPdi/min (p=0.001), which was more pronounced during AC/VT
      ventilation, due to the automatic adjustment of the inspiratory/expiratory time
      ratio. CONCLUSIONS: Increasing the back-up rate during PS and AC/VT ventilation
      decreases respiratory effort in young patients with CF, but this effect was more
      marked with AC/VT ventilation.

PMID- 14727019
TI  - Validation of C1-esterase inhibitor therapy in severe capillary leak syndrome by
      monitoring of extravascular lung water.

PMID- 14727020
TI  - New European directive on clinical trials: implications for traumatic head injury
      research.

PMID- 14727021
TI  - Renal impairment in cardiac surgery patients receiving hydroxyethyl starch.

PMID- 14727022
TI  - Comments on elevated cardiac troponin in patients with COPD.

PMID- 14727023
TI  - Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and
      receptor involvement in cultured islet beta cells.
AB  - AIMS/HYPOTHESIS: It is thought that enterovirus infections cause beta-cell damage
      and contribute to the development of Type 1 diabetes by replicating in the
      pancreatic islets. We sought evidence for this through autopsy studies and by
      investigating known enterovirus receptors in cultured human islets. METHODS:
      Autopsy pancreases from 12 newborn infants who died of fulminant coxsackievirus
      infections and from 65 Type 1 diabetic patients were studied for presence of
      enteroviral ribonucleic acid by in situ hybridisation. Forty non-diabetic control
      pancreases were included in the study. The expression and role of receptor
      candidates in cultured human islets were investigated with receptor-specific
      antibodies using immunocytochemistry and functional assays. RESULTS: Enterovirus
      positive islet cells were found in some of both autopsy specimen collections, but
      not in control pancreases. No infected cells were seen in exocrine tissue. The
      cell surface molecules, poliovirus receptor and integrin alphavbeta3, which act
      as enterovirus receptors in established cell lines, were expressed in beta cells.
      Antibodies to poliovirus receptor, human coxsackievirus and adenovirus receptor
      and integrin alphavbeta3 protected islets and beta cells from adverse effects of
      poliovirus, coxsackie B viruses, and several of the arginine-glycine-aspartic
      acid motifs containing enteroviruses and human parechovirus 1 respectively. No
      evidence was found for expression of the decay-accelerating factor which acts as
      a receptor for several islet-cell-replicating echoviruses in established cell
      lines. CONCLUSIONS/INTERPRETATION: The results show a definite islet-cell tropism
      of enteroviruses in the human pancreas. Some enteroviruses seem to use previously
      identified cell surface molecules as receptors in beta cells, whereas the
      identity of receptors used by other enteroviruses remains unknown.

PMID- 14727024
TI  - ACE-inhibition is superior to endothelin A receptor blockade in preventing
      abnormal capillary supply and fibrosis of the heart in experimental diabetes.
AB  - AIMS/HYPOTHESIS: There is little information whether cardiac capillary supply is
      deranged in diabetes. Hyperglycaemia is a potent stimulus for endothelin-1 (ET-1)
      production. We therefore hypothesised that increased ET-1 production in
      Streptozotocin-induced Type 1 diabetes causes abnormalities of cardiac
      capillaries and the aorta. To this end we compared the effects of an ET receptor
      A blocker (ETA-RB) with that of an ACE-inhibitor (ACE-i) or their combination in
      rats with Streptozotocin (STZ) diabetes. METHODS: Sprague Dawley rats were
      injected with 65 mg STZ i.v. and subsequently developed diabetes. Rats were left
      untreated or received daily either the ACE-i Trandolapril, the ETA-RB Darusentan
      or a combination of both. After 6 months the experiment was terminated and the
      heart and the aorta were investigated using quantitative morphological
      techniques. RESULTS: ACE-i but not ETA-RB lowered blood pressure in STZ Type 1
      diabetic rats. Capillary length density was lower in untreated STZ diabetic rats
      (2932+/-128 mm/mm3) compared to non-diabetic control rats (3410+/-252 mm/mm3).
      Treatment with ACE-i (3568+/-431 mm/mm3), but not with ETA-RB (2893+/-192
      mm/mm3), prevented the decrease in capillary supply. Volume density of the
      myocardial interstitium was higher in untreated STZ diabetic rats (0.86+/-0.04%)
      compared to non-diabetic control rats (0.36+/-0.06%). In all three intervention
      groups the values were lower (ACE-i: 0.53+/-0.05%, ETA-RB: 0.7+/-0.08% and
      combination: 0.69+/-0.1). CONCLUSION/INTERPRETATION: Our study identifies a
      capillary defect of the heart in STZ diabetes, i.e. decreased capillary supply.
      This abnormality was reversed by ACE-i, but not by ETA-R blockade. A similar
      trend, although not complete normalisation, was seen in cardiac fibrosis.

PMID- 14727025
TI  - Acarbose for prevention of diabetes, hypertension and cardiovascular events? A
      critical analysis of the STOP-NIDDM data.
AB  - INTRODUCTION: Cardiovascular morbidity and mortality is a major and still
      unresolved threat to patients with reduced glucose tolerance and Type 2 diabetes
      mellitus. In epidemiological studies, in non-diabetic subjects, post-prandial
      glycaemia is positively associated with the risk of diabetes, hypertension and
      cardiovascular events. If this epidemiological association is causal, Acarbose,
      which reduces post-prandial blood glucose concentrations, should result in a
      decrease in the risk of these events. The STOP-NIDDM trial investigated whether
      Acarbose reduces the risk of diabetes, hypertension and cardiovascular events.
      Consequently, the validity of the results of this trial is of major importance
      for future treatment in non-diabetic and diabetic patients. METHODS: We searched
      various databases and the Internet for publications of the design and the results
      of the STOP-NIDDM trial. A systematic review of these publications was done with
      respect to information about potential sources of bias and contradictory
      information in the articles. RESULTS: We found several serious flaws in the STOP
      NIDDM study, especially selection bias, inadequate blinding, bias in data
      analysis and reporting, and potential sponsoring bias. CONCLUSIONS: The validity
      of the results of the STOP-NIDDM trial is seriously flawed. The clinical benefit
      of Acarbose and of the reduction of post-prandial glycaemia is unproven.

PMID- 14727026
TI  - Detection and verification of quantitative trait loci for resistance to
      Dothistroma needle blight in Pinus radiata.
AB  - Six related radiata pine ( Pinus radiata) full-sib families were used to detect
      and independently verify quantitative trait loci (QTLs) for resistance to
      Dothistroma needle blight, caused by Dothistroma septospora. The detection
      families had from 26 to 30 individuals each, and had either a common maternal
      (31053) or paternal (31032) parent; one family (cross 4) consisted of progeny
      from both parents, 31053 x 31032. Approximately 200 additional progeny from cross
      4 were clonally replicated and planted at two sites, with at least five to seven
      ramets of each individual per site. Marker segregation data were collected from a
      total of 250 RFLP and microsatellite markers, and single factor ANOVAs were
      conducted separately for each family and marker. A number of putative
      associations were observed, some across more than one family. Permutation tests
      were used to confirm expected probabilities of multiple associations based on
      chance alone. Seven markers representing at least four QTLs for resistance to
      Dothistroma were identified as being significant in more than one family; one of
      these was significant at P<0.05 in three families and highly significant at
      P<0.01 in a fourth. Further confirmation was obtained by testing those markers
      that were significant in more than one of the detection families (or highly
      significant in cross 4) in the clonally replicated progeny from cross 4. Four QTL
      positions were verified in the clonal populations, with a total percent variation
      accounted for of 12.5.

PMID- 14727027
TI  - Genetic diversity within Pisum sativum using protein- and PCR-based markers.
AB  - A collection of 148 Pisum accessions, mostly from Western Europe, and including
      both primitive germplasm and cultivated types, was structured using 121 protein-
      and PCR-based markers. This molecular marker-based classification allowed us to
      trace back major lineages of pea breeding in Western Europe over the last
      decades, and to follow the main breeding objectives: increase of seed weight,
      introduction of the afila foliage type and white flowers, and improvement of
      frost tolerance for winter-sown peas. The classification was largely consistent
      with the available pedigree data, and clearly resolved the different main
      varietal types according to their end-uses (fodder, food and feed peas) from
      exotic types and wild forms. Fodder types were further separated into two sub
      groups. Feed peas, corresponding to either spring-sown or winter-sown types, were
      also separated, with two apparently different gene pools for winter-sown peas.
      The garden pea group was the most difficult to structure, probably due to a
      continuum in breeding of feed peas from garden types. The classification also
      stressed the paradox between the narrowness of the genetic basis of recent
      cultivars and the very large diversity available within P. sativum. A sub
      collection of 43 accessions representing 96% of the whole allelic variability is
      proposed as a starting point for the construction of a core collection.

PMID- 14727028
TI  - Microdissection and molecular manipulation of single chromosomes in woody fruit
      trees with small chromosomes using pomelo (Citrus grandis) as a model. I.
      Construction of single chromosomal DNA libraries.
AB  - Construction of single chromosomal DNA libraries by means of chromosome
      microdissection and microcloning will be useful for genomic research, especially
      for those species that have not been extensively studied genetically. Application
      of the technology of microdissection and microcloning to woody fruit plants has
      not been reported hitherto, largely due to the generally small sizes of metaphase
      chromosomes and the difficulty of chromosome preparation. The present study was
      performed to establish a method for single chromosome microdissection and
      microcloning in woody fruit species using pomelo as a model. The standard
      karyotype of a pomelo cultivar ( Citrus grandis cv. Guanxi) was established based
      on 20 prometaphase photomicrographs. According to the standard karyotype,
      chromosome 1 was identified and isolated with fine glass microneedles controlled
      by a micromanipulator. DNA fragments ranging from 0.3 kb to 2 kb were acquired
      from the isolated single chromosome 1 via two rounds of PCR mediated by Sau3A
      linker adaptors and then cloned into T-easy vectors to generate a DNA library of
      chromosome 1. Approximately 30,000 recombinant clones were obtained. Evaluation
      based on 108 randomly selected clones showed that the sizes of the cloned inserts
      varied from 0.5 kb to 1.5 kb with an average of 860 bp. Our research suggests
      that microdissection and microcloning of single small chromosomes in woody plants
      is feasible.

PMID- 14727029
TI  - Characterization of a dwarf gene in Brassica rapa, including the identification
      of a candidate gene.
AB  - Dwarf genes have been valuable for improving harvestable yield of several crop
      plants and may be useful in oilseed Brassica. We evaluated a dwarf gene, dwf2,
      from Brassica rapa in order to determine its phenotypic effects and genetic
      characteristics. The dwf2 mutant was insensitive to exogenous GA(3) for both
      plant height and flowering time, suggesting that it is not a mutation in the
      gibberellin biosynthesis pathway. The dwarf phenotype was controlled by a
      semidominant allele at a single locus. Near-isogenic lines that were homozygous
      or heterozygous for dwf2 had 47.4% or 30.0% reduction in plant height,
      respectively, compared to the tall wild-type line, and the reduction was due to
      reduced internode length and number of nodes. The dwf2 homozygous and
      heterozygous lines had the same or significantly higher numbers of primary
      branches than the wild-type line, but did not differ in flowering time. The DWF2
      gene was mapped to the bottom of linkage group R6, in a region having homology to
      the top of Arabidopsis thaliana chromosome 2. The map position of DWF2 in
      comparison to markers in A. thaliana suggests it is a homolog of RGA ( repressor
      of ga1-3), which is a homolog of the wheat "Green Revolution" gene. This dwarf
      gene could be used to gain more insight on the gibberellin pathway and to reduce
      lodging problems in hybrid oilseed Brassica cultivars.

PMID- 14727030
TI  - Chromosomal location of genes for novel glutenin subunits and gliadins in wild
      emmer wheat (Triticum turgidum L. var. dicoccoides).
AB  - The glutenin and gliadin proteins of wild emmer wheat, Triticum turgidum L. var.
      dicoccoides, have potential for improvement of durum wheat ( T. turgidum L. var.
      durum) quality. The objective of this study was to determine the chromosomes
      controlling the high molecular weight (HMW) glutenin subunits and gliadin
      proteins present in three T. turgidum var. dicoccoides accessions (Israel-A, PI
      481521, and PI-478742), which were used as chromosome donors in Langdon durum- T.
      turgidum var. dicoccoides (LDN-DIC) chromosome substitution lines. The three T.
      turgidum var. dicoccoides accessions, their respective LDN-DIC substitution
      lines, and a number of controls with known HMW glutenin subunits were analyzed by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), urea/SDS
      PAGE, and acid polyacrylamide gel electrophoresis (A-PAGE). The results revealed
      that all three T. turgidum var. dicoccoides accessions possess Glu-A1 alleles
      that are the same as or similar to those reported previously. However, each T.
      turgidum var. dicoccoides accession had a unique Glu-B1 allele. PI-478742 had an
      unusual 1Bx subunit, which had mobility slightly slower than the 1Ax subunit in
      12% SDS-PAGE gels. The subunits controlled by chromosome 1B of PI-481521 were
      slightly faster in mobility than the subunits of the Glu-B1n allele, and the 1By
      subunit was identified as band 8. The 1B subunits of Israel-A had similar
      mobility to subunits 14 and 16. The new Glu-B1 alleles were designated as Glu
      B1be in Israel-A, Glu-B1bf in PI-481521, and Glu-B1bg in PI-478742. Results from
      A-PAGE revealed that PI-481521, PI-478742, and Israel-A had eight, 12, and nine
      unique gliadin bands, respectively, that were assigned to specific chromosomes.
      The identified glutenin subunits and gliadin proteins in the LDN-DIC substitution
      lines provide the basis for evaluating their effects on end-use quality, and they
      are also useful biochemical markers for identifying specific chromosomes or
      chromosome segments of T. turgidum var. dicoccoides.

PMID- 14727031
TI  - Characterisation and marker development for low molecular weight glutenin genes
      from Glu-A3 alleles of bread wheat (Triticum aestivum. L).
AB  - PCR was used to amplify low-molecular-weight (LMW) glutenin genes from the Glu-A3
      loci of hexaploid wheat cultivars containing different Glu-A3 alleles. The
      complete coding sequence of one LMW glutenin gene was obtained for each of the
      seven alleles Glu-A3a to Glu-A3g. Chromosome assignment of PCR products using
      Chinese Spring nulli-tetrasomic lines confirmed the amplified products were from
      chromosome 1A. All sequences were classified as LMW-i-type genes based on the
      presence of an N-terminal isoleucine residue and eight cysteine residues located
      within the C-terminal domain of the predicted, mature amino acid sequence. All
      genes contained a single uninterrupted open reading frame, including the sequence
      from the Glu-A3e allele, for which no protein product has been identified.
      Comparison of LMW glutenin gene sequences obtained from different alleles showed
      a wide range of sequence identity between the genes, with between 1 and 37 single
      nucleotide polymorphisms and between one and five insertion/deletion events
      between genes from different alleles. Allele-specific PCR markers were designed
      based on the DNA polymorphisms identified between the LMW glutenin genes, and
      these markers were validated against a panel of cultivars containing different
      Glu-A3 alleles. This collection of markers represents a valuable resource for use
      in marker-assisted breeding to select for specific alleles of this important
      quality-determining locus in bread wheat.

PMID- 14727032
TI  - Monophyletic origin of naked barley inferred from molecular analyses of a marker
      closely linked to the naked caryopsis gene (nud).
AB  - To elucidate the origin of naked barley, molecular variation of the marker sKT7
      tightly linked to the nud locus was examined. A total of 259 (53 wild, 106 hulled
      domesticated, and 100 naked domesticated) barley accessions were studied.
      Restriction analysis of the sKT7 PCR-amplified product revealed the alleles I,
      II, III, and IV. All four alleles were found in wild barley, but allele IV was
      found only in a single accession from southwestern Iran. Hulled domesticated
      accessions showed alleles I, II, or III, but all naked domesticated accessions
      had allele IV. The distribution of allele IV in wild barley and its pervasive
      presence in naked domesticated lines support the conclusion that naked barley has
      a monophyletic origin, probably in southwestern Iran. The available results
      suggest two scenarios for the origin of naked barley: either directly from a wild
      barley with allele IV or from a hulled domesticated line with allele IV that
      later became extinct. Naked domesticated accessions from different regions of the
      world have extremely homogeneous DNA sequences at the sKT7 locus, supporting the
      monophyletic origin of naked barley. For allele IV, four haplotypes (IVb to IVe)
      were found in 30 naked accessions: IVb was predominant (66.7%) and widely
      distributed, while the other three haplotypes, differing by only one nucleotide
      at different positions relative to IVb, showed a localized distribution. The
      geographical distribution of the haplotypes of sKT7 allele IV suggests migration
      routes of naked domesticated barley in central and eastern Asia.

PMID- 14727033
TI  - Microdissection and molecular manipulation of single chromosomes in woody fruit
      trees with small chromosomes using pomelo (Citrus grandis) as a model. II.
      Cloning of resistance gene analogs from single chromosomes.
AB  - Amplification of resistance gene analogs (RGAs) is both a useful method for
      acquiring DNA markers closely linked to disease resistance (R) genes and a
      potential approach for the rapid cloning of R genes in plants. However, the
      screening of target sequences from among the numerous amplified RGAs can be very
      laborious. The amplification of RGAs from specific chromosomes could greatly
      reduce the number of RGAs to be screened and, consequently, speed up the
      identification of target RGAs. We have developed two methods for amplifying RGAs
      from single chromosomes. Method 1 uses products of Sau3A linker adaptor-mediated
      PCR (LAM-PCR) from a single chromosome as the templates for RGA amplification,
      while Method 2 directly uses a single chromosomal DNA molecule as the template.
      Using a pair of degenerate primers designed on the basis of the conserved
      nucleotide-binding-site motifs in many R genes, RGAs were successfully amplified
      from single chromosomes of pomelo using both these methods. Sequencing and
      cluster analysis of RGA clones obtained from single chromosomes revealed the
      number, type and organization of R-gene clusters on the chromosomes. We suggest
      that Method 1 is suitable for analyzing chromosomes that are unidentifiable under
      a microscope, while Method 2 is more appropriate when chromosomes can be clearly
      identified.

PMID- 14727034
TI  - Multicolor FISH mapping of the dioecious model plant, Silene latifolia.
AB  - Silene latifolia is a key plant model in the study of sex determination and sex
      chromosome evolution. Current studies have been based on genetic mapping of the
      sequences linked to sex chromosomes with analysis of their characters and
      relative positions on the X and Y chromosomes. Until recently, very few DNA
      sequences have been physically mapped to the sex chromosomes of S. latifolia. We
      have carried out multicolor fluorescent in situ hybridization (FISH) analysis of
      S. latifolia chromosomes based on the presence and intensity of FISH signals on
      individual chromosomes. We have generated new markers by constructing and
      screening a sample bacterial artificial chromosome (BAC) library for appropriate
      FISH probes. Five newly isolated BAC clones yielded discrete signals on the
      chromosomes: two were specific for one autosome pair and three hybridized
      preferentially to the sex chromosomes. We present the FISH hybridization patterns
      of these five BAC inserts together with previously described repetitive sequences
      (X-43.1, 25S rDNA and 5S rDNA) and use them to analyze the S. latifolia
      karyotype. The autosomes of S. latifolia are difficult to distinguish based on
      their relative arm lengths. Using one BAC insert and the three repetitive
      sequences, we have constructed a standard FISH karyotype that can be used to
      distinguish all autosome pairs. We also analyze the hybridization patterns of
      these sequences on the sex chromosomes and discuss the utility of the karyotype
      mapping strategy presented to study sex chromosome evolution and Y chromosome
      degeneration.

PMID- 14727035
TI  - [Diagnostics at the wrist].
AB  - Injuries of the wrist are difficult to diagnose because of the complex and narrow
      anatomic structures. Based on precise clinical examination, X-rays, CT, and MRI
      are valuable additional tools that can be used. If a fracture is suspected a CT
      scan is preferable. In the case of a suspected soft tissue or ligamentous injury
      and non-vital fragments or necrosis MRI is suitable. Other diagnostic tools are
      presently of minor importance for the wrist. Technical innovations allow better
      visualization and classification of lesions. However, exact knowledge of the
      tools is important.

PMID- 14727036
TI  - [Proximal row carpectomy: a motion-preserving procedure in the treatment of
      advanced carpal collapse].
AB  - Proximal row carpectomy (PRC) is a motion-sparing procedure for the treatment of
      advanced carpal collapse. The goal of the operation is the creation of a new
      joint between the capitate and the radius. The purpose of this retrospective
      study was the evaluation of the functional outcome after PRC. The evaluation
      included range of motion, grip strength, and pain reduction. The DASH
      questionnaire was used to estimate restrictions of the activities of daily living
      (ADL). Results were ranked with the Mayo and Krimmer wrist scores. Thirty-three
      patients with a mean age of 41.2 years were evaluated after 36 months.
      Flexion/extension was 70 degrees and radial and ulnar deviation was 33 degrees.
      The grip strength was 54% of the unaffected side. The results of Mayo and Krimmer
      wrist scores were 66 and 69 points. The mean DASH score was 27.8. Eighty-seven
      percent of the patients reported that pain was better than preoperatively.
      Resection of the proximal carpal row is technically an easy surgical procedure.
      It preserves good functional range of motion and provides good pain relief, but
      low grip strength.

PMID- 14727037
TI  - [Patellectomy after trauma: is there a correlation between the timing and the
      clinical outcome].
AB  - AIM OF THE STUDY: Is there a correlation between the timing of patellectomy after
      trauma in crush injuries and the clinical outcome? METHODS: Retrospective
      analysis of 21 patients who had undergone patellectomy after trauma. RESULTS: In
      12 patients (57.1%) a primary patellectomy was performed within 4 weeks after the
      fracture; in the remaining 9 (42.9%) patients the procedure was performed after
      an average of 21 months (range 2-72). Nineteen patients could be followed up
      after 9.3 years (range 3-18). In 10 of these, patellectomy had been performed
      primarily. The HSS Knee Score was 68.4 points (range 39-83) on average for all
      patients. For patients with a primary patellectomy the score was 71 points (range
      54-83), while for patients in whom the patellectomy was performed secondarily the
      score was 63.8 points (range 39-77). The evaluated ROM was 113.6 degrees for all
      patients; in the primary group ROM was 122.5 degrees (range 65-145 degrees ), and
      in the secondary group it was 103 degrees (range 85-145 degrees ). The difference
      was not statistically significant for either parameter. CONCLUSION: Primary
      reconstruction of the patella is recommended in multifragmentary fractures; if
      the outcome is poor, however, patellectomy should be considered early.

PMID- 14727038
TI  - [Prevention of thromboembolism in trauma surgery by dose adjustment of low
      molecular weight heparin depending on levels of TAT and D-dimer].
AB  - Deep vein thrombosis (DVT) is reported in up to 40% of trauma patients. The
      individual risk is nearly unpredictable. A daily single dose of a low molecular
      weight heparin (LMWH) was administered as prophylaxis to 518 trauma patients who
      were examined preoperatively and up to 10 days postoperatively in a prospective
      study. They were divided into two groups: group I comprised surgery of the hip
      and femur as well as total knee replacement and group II knee and lower leg
      surgery. Thrombin-antithrombin complex and D-dimer were analyzed. A second daily
      dose of LMWH was added if D-dimer exceeded the cutoff. If ultrasound was
      suspicious for DVT venography was added. Deep vein thrombosis was seen in five
      cases (group I=4, group II=1), without pulmonary embolism. TAT and D-dimer were
      significantly higher in group I than in group II ( p<0.005). One hundred
      patients, 79 of them belonging to group I, were treated with a second dose of
      LMWH. The daily cutoff had the highest sensitivity and specificity for day 4. Due
      to individual monitoring of coagulation markers, the risk for thromboembolism
      compared to actual data in the literature seems to be reduced.

PMID- 14727039
TI  - [Traumatic atlanto-axial rotatory fixation with lateral mass fracture of the
      axis].
AB  - Traumatic atlanto-axial rotatory fixation (AARF) is a relatively uncommon injury,
      especially in association with fractures of the axis. The rotatory dislocation
      and fixation is normally caused by intercalated facet joints of axis and atlas. A
      traumatic AARF in a 21 year old female is presented with special emphasis on the
      diagnostic and therapeutic approaches. This high velocity injury was caused by a
      traffic accident. The trauma service which was initially involved made the
      correct diagnosis and tried to reduce the dislocation by skull traction during
      analgesia and sedation, but without success. For further treatment, the patient
      was referred to a level one trauma center. After completing the diagnostic
      imaging with MRI and CT for exact delineation of the fracture site and
      determination of ligament damage, a halo fixation for skull traction was
      installed. This second attempt was also unsuccessful. Only a closed reduction
      under general anesthesia with muscle relaxation led to a neutral alignment and
      congruent joint contact between C1 and C2. Due to the stable fracture site and
      the intact ligaments, a conservative treatment with a stable collar splint was
      performed.

PMID- 14727040
TI  - [Total knee replacement for primary treatment of intra-articular tibial head
      fractures in elderly patients].
AB  - Intra-articular fractures of the tibial head pose a huge challenge for the
      surgeon. An increase of these fractures, especially in the elderly, has been
      observed in recent years. The cause of injury in the elderly is in most cases a
      slight trauma. The mechanism of dislocation plays only a subordinated role. These
      are serious injuries of the bone, which are accompanied by soft tissue lesions.
      Furthermore, there are some factors, which could have a negative effect on the
      treatment, such as osteoporosis, diseases of the vascular system, osteoarthrosis,
      limited coordination, and insufficient autologous cancellous bone. Every surgeon
      is aware of secondary, clinically relevant deficits after operative treatment of
      the tibial head in the elderly. We treated two elderly patients with different
      additional findings by total knee replacement.

PMID- 14727041
TI  - [Spontaneous patellar tendon rupture in a patient with Ehlers-Danlos syndrome].
AB  - The operative treatment of patellar tendon ruptures in patients with Ehlers
      Danlos syndrome is complicated by the reduced mechanical properties of the
      tissue. These make it necessary to use, in addition to an end-to-end suture of
      the debrided tendon stumps and temporary stabilization by a McLaughlin cerclage,
      an additional augmentation, for example a Trevira band.

PMID- 14727042
TI  - [Ossiculum terminale (Bergmann). Differential diagnosis of an odontoid fracture
      of the Anderson I type].
AB  - We describe a case of the rare entity of a persistent ossicle on the top of the
      odontoid process. In a short review of the literature, we show developmental
      abnormalities of the odontoid process and its etiologies. The terminal ossicle
      (Bergmann) plays an important role in the differential diagnosis of a fracture of
      the odontoid process type I in adults using the classification of Anderson and
      D'Alonzo. If fracture and instability is excluded by plain radiographs, computed
      tomography and/or MRI, there is no need for additional therapy.

PMID- 14727043
TI  - [Meta-analysis. A meaningful tool for evidence-based (intensive) medicine].

PMID- 14727044
TI  - [Endotoxins. Pathogenetic meaning of sepsis].

PMID- 14727045
TI  - [Surgical concepts for treatment of severe sepsis].

PMID- 14727046
TI  - [Early goal-directed therapy in sepsis. Old wine in new skins?].

PMID- 14727047
TI  - [Intensive insulin therapy in sepsis. Improvement of survival chances?].

PMID- 14727049
TI  - [Activated protein C. Inevitable in sepsis?].

PMID- 14727048
TI  - [Cortisone substitution in sepsis. Is less more?].

PMID- 14727050
TI  - [Continuous dialysis and hemofiltration. More than a kidney replacement method?].

PMID- 14727051
TI  - Direct organogenesis of Mandevilla illustris (Vell) Woodson and effects of its
      aqueous extract on the enzymatic and toxic activities of Crotalus durissus
      terrificus snake venom.
AB  - In order to produce explants of Mandevilla illustris (Vell) Woodson for the
      "Cerrado in vitro", the Germplasm Bank of UNAERP, we carried out a
      micropropagation protocol using MS or MS/3 medium supplemented with different
      concentrations of 6-benzyladeninepurine (BA), Zeatin or 2-isopentenyladenine for
      nodal segment growth, and alpha-naphthaleneacetic acid, indole-3-butyric acid
      (IBA) or 1,4 dithiothreitol for rooting. For nodal segments, all the cytokinins
      tested yielded similar results. However, 2.22 micro M BA is more economical to
      use. MS/3 medium supplemented with 0.49 micro M IBA was the most appropriate
      medium for rooting, resulting in 29% rooted explants. The crude aqueous extract
      from the subterranean system (SS) of M. illustris was assayed for its inhibitory
      action on the enzymatic activity of Crotalus durissus terrificus snake venom,
      isolated basic phospholipase A2 (CB) and crotoxin. It totally inhibited the
      phospholipase activity of crude Cdt venom and CB toxin and inhibited the
      phospholipase activity of crotoxin by 49%. The toxic action of both the crude
      venom and crotoxin was partially inhibited-there was a prolonged survival time
      and a 40.0% decrease in lethality.

PMID- 14727052
TI  - Penicillin derivatives induce chemical structure-dependent root development, and
      application for plant transformation.
AB  - We investigated five penicillin derivatives that are popularly used for
      transformation experiments with Agrobacterium rhizogenes-penicillin G,
      carbenicillin, ampicillin, amoxicillin and cephalexin-for their effects on the
      growth and morphology of Beta vulgaris, Capsicum annuum and Glehnia littoralis
      roots. Attention was given to the relationship between their chemical structures
      and functions. Ampicillin was found to stimulate root elongation but inhibit root
      branching, whereas carbenicillin inhibited root elongation but promoted root
      branching. Root cultures were also exposed to hydrolyzed products of these
      antibiotics-i.e. phenylmalonic acid (PM), phenylglycine and 6-aminopenicillanic
      acid (6-APA): PM inhibited root elongation the most, while root elongation was
      supported best by 6-APA. These results indicate that both the side chains and the
      major component of penicillin derivatives affect root development and that the
      nature of the side chains is responsible for the responses. Ampicillin but not
      carbenicillin was used in subsequent experiments described herein to eliminate
      bacteria and to support root growth of transformants of the recalcitrant plants.

PMID- 14727053
TI  - Pearl millet transformation system using the positive selectable marker gene
      phosphomannose isomerase.
AB  - Fertile transgenic pearl millet plants expressing a phosphomannose isomerase
      (PMI) transgene under control of the maize ubiquitin constitutive promoter were
      obtained using the transformation system described here. Proliferating immature
      zygotic embryos were used as target tissue for bombardment using a particle
      inflow gun. Different culture and selection strategies were assessed in order to
      obtain an optimised mannose selection protocol. Stable integration of the manA
      gene into the genome of pearl millet was confirmed by PCR and Southern blot
      analysis. Stable integration of the manA transgene into the genome of pearl
      millet was demonstrated in T1 and T2 progeny of two independent transformation
      events with no more than four to ten copies of the transgene. Similar to results
      obtained from previous studies with maize and wheat, the manA gene was shown to
      be a superior selectable marker gene for improving transformation efficiencies
      when compared to antibiotic or herbicide selectable marker genes.

PMID- 14727054
TI  - The German Short Musculoskeletal Function Assessment questionnaire: reliability,
      validity, responsiveness, and comparison with the Short Form 36 and Constant
      score--a prospective evaluation of patients undergoing repair for rotator cuff
      tear.
AB  - In a prospective clinical trial, first the German Short Musculoskeletal Function
      Assessment questionnaire (SMFA-D) was tested for reliability, validity, and
      responsiveness in 23 patients with rotator cuff tears, and secondly the Short
      Form (SF)-36, and the Constant score were evaluated comparatively in 45 patients
      with rotator cuff tear undergoing open repair. Retest reliability was excellent
      for the functional index of the SMFA-D and satisfactory for the bother index. The
      SMFA-D showed good validity and responsiveness. All three instruments
      demonstrated significantly the positive effect of rotator cuff repair at 12-month
      follow-up. Using comparable scales, effect sizes were bigger with the SMFA-D than
      with the SF-36 and as big as the Constant score. Significant correlations of the
      SMFA-D indices with the SF-36 scales and the Constant score could be shown
      preoperatively. At 12-month follow-up, all correlations between SMFA-D indices,
      SF-36 scales, and Constant score function scales were still significant. We
      recommend use of the SMFA-D to assess changes in functional status concerning
      patients with rotator cuff tear undergoing open repair.

PMID- 14727055
TI  - Sensorineural hearing loss in a patient with ankylosing spondylitis.

PMID- 14727056
TI  - Calcium and vitamin D supplementation failed to improve bone mineral density in
      Indo-Asians suffering from hypovitaminosis D and secondary hyperparathyroidism.
AB  - BACKGROUND: The association of low bone mineral density (BMD) in Asians with
      hypovitaminosis D (HD) and when complicated with secondary hyperparathyroidism
      (HD-SHPT) has been shown previously. OBJECTIVE: Our aim was to study the
      effectiveness of calcium and vitamin D therapy in Indo-Asians with HD and HD
      SHPT. METHODS: One hundred forty-three patients attending our rheumatology
      clinic, including 97 (68%) with HD aged 48.9+/-11.6 years (86% female) and 46
      (32%) with HD-SHPT aged 55.9+/-12.6 years (85% female), were recruited. Baseline
      investigations included routine biochemistry and 25-hydroxy vitamin D [25(OH)D],
      and parathyroid hormone (PTH) assays. Bone mineral densities (BMDs) of femoral
      neck, lumbar spine (LS), and distal radius (DR) were measured by dual energy X
      ray absorptiometry. Patients were commenced on 1.0-1.25 g of calcium plus 400 IU
      of vitamin D. Blood tests were repeated at 6 and 12 months. Thirty-six patients
      with t scores of <-1 had their BMDs remeasured at 2 years. Unpaired t- and Mann
      Whitney U tests were used in statistics. Results were considered significant at
      P< or =0.05. RESULTS: Femur t and z scores failed to improve in either group. The
      reduction in LS t scores but not z scores was significant in both groups.
      Significant reductions in DR t and z scores occurred in the HD group only.
      Calcium and 25(OH)D increased significantly in both groups. Alkaline phosphatase
      and PTH were suppressed significantly only in HD-SHPT. CONCLUSION: The failure of
      BMD to improve could be due to lack of compliance with medication between years 1
      and 2, when most patients were under the supervision of primary care. To overcome
      this, we recommend continuance of blood monitoring at least once a year.

PMID- 14727057
TI  - MEFV mutations in familial Mediterranean fever: association of M694V homozygosity
      with arthritis.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive recurrent
      polyserositis with a higher prevalence in some ethnic groups, including Turks.
      Mutations in the FMF gene (MEFV) were found associated with FMF. The aim of this
      study was to analyze MEFV gene mutations in FMF patients to gain insight into the
      mutation phenotype correlation. OBJECTIVES: We analyzed the most frequent
      mutations (M680I, M694V, V726A, and E148Q) in a group of young male Turkish FMF
      patients using an amplification refractory mutation system and a commercial kit.
      RESULTS: M694V mutation was detected in 80% of the patients. After making a
      strict diagnostic discrimination between arthralgia and arthritis, arthritis was
      present in 71% of homozygous and 29.4% of heterozygous patients for M694V
      mutation. Other mutations were not found to correlate with specific symptoms or
      findings. CONCLUSION: The homozygosity of M694V mutation in the MEFV gene is
      associated with arthritis in FMF patients.

PMID- 14727059
TI  - Disruption of the Aspergillus fumigatus argB gene using a novel in vitro
      transposon-based mutagenesis approach.
AB  - We disrupted the Aspergillus fumigatus argB gene, encoding ornithine
      transcarbamylase, using a novel in vitro transposon-based mutagenesis approach.
      This approach utilizes a modified transposon containing the Neurospora crassa
      pyr4 gene, which is randomly inserted in vitro into a target sequence of
      interest. Clones in which the gene of interest has been disrupted are identified
      by PCR and used to transform a pyrG-deficient strain of A. fumigatus. Using this
      approach, we obtained arginine auxotrophs of A. fumigatus. Full characterization
      of the argB insertion was performed by Southern blot analysis. These strains can
      be supplemented by addition of arginine into the culture medium and can be fully
      rescued to arginine prototrophy by transformation with the intact A. fumigatus
      argB gene.

PMID- 14727058
TI  - Analysis of a nonribosomal peptide synthetase gene from Alternaria brassicae and
      flanking genomic sequences.
AB  - Very little information is currently available concerning the pathogenic
      determinants produced by Alternaria brassicae, the causal agent of the blackspot
      disease of crucifers. We screened a genomic library of this fungus and identified
      a nonribosomal peptide synthetase (NRPS) gene named AbrePsy1. The complete coding
      sequence is 22 kbp long and encodes a large protein (792 kDa) showing typical
      NRPS modular organization. Structural analysis of AbrePsy1 revealed four complete
      elongation modules, two of which have epimerization domains. In the vicinity of
      AbrePsy1, a second gene (named AbreAtr1), which encodes an ATP-binding cassette
      transporter was identified. Increased expression of AbrePsy1 and AbreAtr1 was
      observed during host-plant infection. However, while physically linked, these two
      genes are probably not functionally clustered, as their expression patterns
      differed.

PMID- 14727060
TI  - A fission yeast strain expressing human CDC25A phosphatase: a tool for
      selectivity studies of pharmacological inhibitors of CDC25.
AB  - Fission yeast is a simple eukaryotic model organism in which many aspects of cell
      cycle control can be explored. We examined by homologous recombination whether
      the human CDC25A phosphatase could substitute for the function of the fission
      yeast Cdc25. We first show: (a). that CDC25A efficiently replaces the endogenous
      Cdc25 mitotic inducer for vegetative growth and (b). that CDC25A is able to
      partially restore a functional checkpoint in response to both ionising and UV
      irradiation, but not a DNA replication checkpoint. We then describe a simple
      assay in which we demonstrate that growth of the humanised CDC25A strain is
      strongly repressed in a CDC25-dependent manner by BN2003, a potent chemical
      inhibitor of CDC25 belonging to the benzothiazoledione family. The ease of
      manipulation of fission yeast humanised CDC25 cells and the simplicity of the
      above assay offer a powerful tool with which to investigate the specificity of
      pharmacological inhibitors of CDC25.

PMID- 14727062
TI  - Damage control laparotomy for generalized necrotizing enterocolitis.
AB  - Macroscopic generalized necrotizing enterocolitis (G-NEC) is associated with a
      very high mortality in neonates. In some instances, however, multiple bowel
      segments are necrotic, with most of the remaining small bowel damaged but viable.
      In these selected patients morbidity can be reduced and survival increased with
      an aggressive and early surgical approach. We have termed this approach damage
      control laparotomy (DCL). Over a 5(1/2)-year period, all neonates with G-NEC with
      adequate length of viable small bowel were subjected to DCL. The procedure is
      characterized by a resuscitative period of a few hours followed by laparotomy and
      resection of dead/perforated bowel. The bowel ends are either anastomosed or
      tied, and the bowel is returned to the abdomen to allow full tissue demarcation.
      Re-look laparotomy is performed 3-4 days later, at which time any new necrotic
      bowel is excised and re-joined, to achieve small bowel continuity. In this
      prospective study, 104 neonates with G-NEC underwent operation; 27 neonates (26%)
      were considered to have an adequate potential length of viable bowel and were
      selected for DCL. Nineteen neonates survived in the follow-up period. Early
      mortality was due to sepsis syndrome in 6 patients, and late mortality in 2
      neonates was secondary to the short bowel syndrome. The DCL procedure is another
      step toward improving survival in surgical G-NEC; this technique avoids proximal
      stomas and their complications, and at the same time it preserves the best
      possible bowel length.

PMID- 14727063
TI  - Total thyroidectomy (TT) for management of benign thyroid disease.

PMID- 14727064
TI  - Barrett's esophagus: histopathologic definitions and diagnostic criteria.
AB  - Adenocarcinoma of the distal esophagus is rising more rapidly in incidence than
      any other visceral malignancy in the Western world. It is well established that
      most, if not all, of these tumors develop in Barrett's esophagus via the
      metaplasia-dysplasia-carcinoma sequence and could theoretically be detected at an
      early stage, but despite this, the majority of these tumors are still detected
      late in their course. This highlights the fact that the goal of effective
      surveillance for patients at risk for developing an adenocarcinoma of the distal
      esophagus is still far off. In addition, adenocarcinomas of the esophagogastric
      junction and gastric cardia are also rising in incidence, but their
      carcinogenesis and their relation to Barrett's esophagus are still being defined,
      as are the meaning and significance of the relatively new entities "short-segment
      Barrett's" and "ultra-short-segment Barrett's". This review attempts to clarify
      the main histopathologic issues concerned with the definition of Barrett's
      esophagus, its distinction from intestinal metaplasia of the gastric cardia, as
      well as the criteria for the histologic diagnosis of dysplasia and carcinoma in
      Barrett's esophagus.

PMID- 14727065
TI  - Rectus abdominis muscle flap for high-output duodenal fistula: novel technique.
AB  - Duodenal fistula after closure of peptic ulcer perforation, though rare, is
      difficult to manage and carries a high mortality. The high mortality is
      associated with the poor nutritional status of the patient, high output from the
      fistula, and late development of peritonitis and septicemia. The various
      techniques described in the literature for the closure of the postsurgical
      external duodenal fistulas range from conservative management with total
      parenteral nutrition (TPN), serosal patch repair, and Roux-en- Y procedures to
      radical surgery like Billroth II gastrectomy. Total parenteral nutrition achieves
      spontaneous closure in 70% to 80% of cases, but it is very expensive and requires
      prolonged hospitalization. In addition, some surgical procedures have yielded
      poor results in our setting, so we sought a new modality of treatment. We
      describe a novel technique for repair of postsurgical external fistula of the
      duodenum with a rectus abdominis muscle flap. The rectus abdominis muscle is
      detached from its superior attachment and mobilized from the rectus sheath. The
      flap, based on the deep inferior epigastric artery, is raised and sutured to the
      duodenal fistula with thick silk sutures. We treated six patients with post
      surgical duodenal fistulas with this technique between 1995 and 2002. The leak
      was completely sealed in all patients. One patient died of septicemia. We
      recommend this technique for the management of postsurgical external duodenal
      fistula as an alternative to other surgical techniques.

PMID- 14727073
TI  - Resolving conflict and building cooperation in the National Estuary program.
AB  - Since its beginning in 1987, researchers and policymakers have touted the US
      Environmental Protection Agency National Estuary program (NEP) as one of the
      leading examples of collaborative institutions designed to resolve conflict and
      build cooperation at the watershed level. Using the NEP as an example, I
      summarize the advantages and disadvantages of collaborative institutions. Using
      data gathered from focused surveys of policy elites in 22 estuaries, I estimate
      statistical models that show the NEP does a better job of resolving conflict and
      building project-level cooperation than similar estuaries without the NEP. I also
      describe the activities of the NEP mentioned by respondents as contributing to
      this outcome.

PMID- 14727080
TI  - Functional and esthetic rhinoplasty.
AB  - Rhinoplasty is performed to improve the appearance of the nose. However,
      conventional procedures may result in impairment of nasal breathing. The purpose
      of this article is to describe a "functional and esthetic" rhinoplasty technique
      designed to avoid adverse effects on ventilation by preserving the structure of
      the nasal vault. The main indication for this technique is treatment of cyphotic
      or tension nose. Since this procedure does not correct nasal obstruction due to
      septo-turbinal abnormalities and narrow nasal fossa, turbinoplasty must be
      performed concurrently if necessary. Our series of >1000 cases over a 15-year
      period demonstrates that this conservative rhinoplasty technique prevents most
      functional complications associated with conventional procedures and often
      improves ventilation. Immediate and long-term cosmetic outcome is excellent with
      a natural-looking appearance and fewer tip revisions.

PMID- 14727081
TI  - Surgical correction of retracted nostril rim with auricular composite grafts and
      anchoring suspention.
AB  - Among concerned nasal appearances, a deformity with supero-lateral displacement
      of the nostril rim, called retracted nostril rim or elevated nostril rim is
      commonly seen and is considered one of the most difficult types of cases to treat
      aesthetically. A new surgical method for treating retracted nostril rim was
      performed in 10 patients, using the combination of auricular composite graft,
      internal fixation with a retainer, and external continuing suspension with
      anchoring sutures. The procedure was successful in maintaining the grafted
      cartilage in the ideal position and in avoiding recurrence of retraction or
      elevation of the constructed alar rim. The presented method merits consideration
      as a standard operative approach for correction of retracted nostril rim.

PMID- 14727083
TI  - Selective instrumentation, reduction and repair in low-grade isthmic
      spondylolisthesis.
AB  - We treated 32 patients with low-grade (<30%) isthmic spondylolisthesis at L5-S1
      with selective instrumentation, reduction of the slip, resection of the
      pseudoarthrosis adding autologous bone grafting and decompressing the root canal.
      The ages ranged from 18 to 54 years. After a mean of 3.4 (1-7) years, we found
      good radiological and clinical results in 27 patients. Five patients lost
      correction, of whom three were asymptomatic whereas two required fusion of L5-S1.
      We think this technique is a useful surgical option for select patients.

PMID- 14727084
TI  - Identification of tumor antigens as potential target antigens for immunotherapy
      by serological expression cloning.
AB  - The presence of tumor infiltrating T cells has been shown to be associated with a
      favorable prognosis in different tumor types. Several strategies have been
      developed to identify relevant tumor antigens which can be used for active
      immunotherapy strategies. The SEREX technique (serological analysis of cDNA
      expression libraries) identifies tumor antigens based on a spontaneous humoral
      immune response in cancer patients. This technique is not limited to tumor types
      that can be grown in cell culture or depends on established T cell clones
      recognizing the autologous tumor. Several steps of analysis are mandatory to
      evaluate SEREX-defined antigens before they become new target antigens for active
      immunotherapy: expression analysis; serological analysis with sera from tumor
      patients and normal individuals; identification of potential peptide epitopes for
      CD8 T cells and evaluation in T cell assays. This article summarizes our approach
      of antigen identification and evaluation giving the example of the recently
      cloned breast cancer antigen NY-BR-1.

PMID- 14727085
TI  - Exosome-based immunotherapy.
AB  - Exosomes are small membrane vesicles originating from late endosomes and secreted
      by hematopoietic and epithelial cells in culture. Exosome proteic and lipid
      composition is unique and might shed some light into exosome biogenesis and
      function. Exosomes secreted from professional antigen-presenting cells (i.e., B
      lymphocytes and dendritic cells) are enriched in MHC class I and II complexes,
      costimulatory molecules, and hsp70-90 chaperones, and have therefore been more
      extensively studied for their immunomodulatory capacities in vitro and in vivo.
      This review will present the main biological features pertaining to tumor or DC
      derived exosomes, will emphasize their immunostimulatory function, and will
      discuss their implementation in cancer immunotherapy.

PMID- 14727086
TI  - Rhabdomyosarcomas are potential target of MAGE-specific immunotherapies.
AB  - The search for alternative strategies of therapy remains a major issue for most
      neoplastic diseases. The expression of several tumor antigens makes human
      rhabdomyosarcomas, which are the most frequent form of soft tissue tumor in
      children, a good candidate for tumor-specific immunotherapy. To assess the
      feasibility of this approach, we evaluated the ability of rhabdomyosarcoma cell
      lines to process and present the MAGE-A tumor antigens to effectors of the immune
      system. To this end, we investigated recognition of MAGE-A-positive
      rhabdomyosarcoma cells by HLA-B*3701-restricted T cells specific for a MAGE-A
      derived peptide. Low level of HLA expression impaired recognition of the tumor
      cells. Therefore, to obtain HLA expression avoiding the use of IFN-gamma and TNF
      alpha, which could affect the proteasome activity, a rhabdomyosarcoma line was
      transduced by a retroviral vector encoding the HLA-B*3701 allele. Recognition of
      the infected cells was then observed also in the absence of IFN-gamma and TNF
      alpha treatment, thus demonstrating that rhabdomyosarcoma cells were indeed able
      to naturally process and present the MAGE-A antigens. These results demonstrate
      that rhabdomyosarcoma cells expressing MAGE-A can be targets of tumor-specific
      effectors, suggesting the feasibility of clinical protocols of specific
      immunotherapy also for the treatment of rhabdomyosarcoma.

PMID- 14727087
TI  - Down-regulation of HLA class II and costimulatory CD86/B7-2 on circulating
      monocytes from melanoma patients.
AB  - Antigen-presenting cells are crucial for the induction of an antigen-specific
      antitumoral immune response. Deteriorations in the expression pattern of cell
      surface molecules important for the presentation of antigens might therefore be
      indicative of an impaired immune response status in cancer patients. In the
      present study we investigated the expression of MHC class I and class II
      molecules, of the costimulatory molecules CD80/B7-1 and CD86/B7-2, of the
      adhesion molecule CD11c, and of the marker of activation CD71 on CD14+ peripheral
      blood monocytes (PBMs) from 144 melanoma patients in different stages of disease
      and 43 healthy controls, by flow cytometric analysis. We found a decreased
      expression of HLA-DR (p<0.0005), HLA-DQ (p=0.006), HLA-DP (p<0.0005), and CD86/B7
      2 (p=0.001) on PBMs from melanoma patients compared with healthy controls,
      whereas no significant difference could be detected in the expression of HLA
      class I antigens and CD80/B7-1. This down-regulated expression was associated
      with disease progression. In contrast, CD71 expression was stage-dependently
      increased on PBMs from melanoma patients compared with healthy controls
      (p=0.024). No correlation was found between the PBM surface expression pattern
      and age, gender, tumor load, and current mode of therapy of the patients. The
      observed down-regulation of HLA class II and CD86/B7-2 on melanoma patients' PBMs
      might reflect an ineffective antigen-presenting function contributing to an
      impaired antigen-specific immune response in these patients.

PMID- 14727088
TI  - Biodegradation of alachlor by soil streptomycetes.
AB  - Streptomycetes resistant to the herbicide alachlor [2-chloro-2',6'-diethyl- N
      (methoxymethyl) acetanilide] were used in degradation assays to characterize the
      products of alachlor biodegradation. Of six strains tested, Streptomyces sp.
      LS166, LS177, and LS182 were able to grow at an alachlor concentration of 144 mg
      l(-1) and degraded approximately 60-75% of the alachlor in 14 days, as evaluated
      by high performance liquid chromatography. The alachlor biodegradation products
      were identified by gas chromatography-mass spectrometry based on mass spectral
      data and fragmentation patterns. All compounds detected in these assays were
      similar for all streptomycetes strains tested, and involved dechlorination with
      subsequent N-dealkylation and cyclization of the remaining N-substituent with one
      of the ethyl groups to produce indole and quinoline derivatives. The enzymatic
      pathway used by Streptomyces sp. LS182 did not generate DEA (2',6'
      diethylaniline), a carcinogenic derivative of alachlor reported in other studies.
      Given the high degradation rates observed here, the Streptomyces strains tested
      may be useful in the degradation/detoxification processes of alachlor.

PMID- 14727089
TI  - Gene expression in Escherichia coli biofilms.
AB  - DNA microarrays were used to study the gene expression profile of Escherichia
      coli JM109 and K12 biofilms. Both glass wool in shake flasks and mild steel 1010
      plates in continuous reactors were used to create the biofilms. For the biofilms
      grown on glass wool, 22 genes were induced significantly (p< or =0.05) compared
      to suspension cells, including several genes for the stress response ( hslS,
      hslT, hha, and soxS), type I fimbriae ( fimG), metabolism ( metK), and 11 genes
      of unknown function ( ybaJ, ychM, yefM, ygfA, b1060, b1112, b2377, b3022, b1373,
      b1601, and b0836). The DNA microarray results were corroborated with RNA dot
      blotting. For the biofilm grown on mild steel plates, the DNA microarray data
      showed that, at a specific growth rate of 0.05/h, the mature biofilm after 5 days
      in the continuous reactors did not exhibit differential gene expression compared
      to suspension cells although genes were induced at 0.03/h. The present study
      suggests that biofilm gene expression is strongly associated with environmental
      conditions and that stress genes are involved in E. coli JM109 biofilm formation.

PMID- 14727090
TI  - Liquid culture mass production of biocontrol nematodes, Heterorhabditis
      bacteriophora (Nematoda: Rhabditida): improved timing of dauer juvenile
      inoculation.
AB  - Heterorhabditis bacteriophora is used in biological control of soil-borne insect
      pests in horticulture and turf. Mass production is carried out in monoxenic
      liquid cultures pre-incubated with the symbiont of the nematodes, the bacterium
      Photorhabdus luminescens, before nematode dauer juveniles (DJ) are inoculated. As
      a response to bacterial food signals, the DJ recover from the developmentally
      arrested dauer stage, grow to adults and produce DJ offspring. Variable DJ
      recovery after inoculation into cultures of P. luminescens often causes process
      failure due to low numbers of adult nematodes in the medium. In order to enhance
      DJ recovery, improve nematode population management and increase yields, the
      optimal timing for DJ inoculation was sought. The process parameter pH and
      respiration quotient (RQ) were recorded in order to test whether changes can be
      used to identify the best moment for DJ inoculation. When DJ were inoculated
      during the lag and early logarithmic growth phases of P. luminescens cultures, DJ
      recovery was low and almost no nematode reproduction was obtained. High
      populations of P. luminescens phase variants were recorded. Recovery and yields
      increased when DJ were inoculated during the latter log phase during which the RQ
      dropped to values <0.8 and the pH reached a maximum. The highest DJ recovery and
      yields were observed in cultures that were inoculated during the late stationary
      growth phase. This period started with the increase of the pH after its distinct
      minimum at pH <8.0. Thus optimal timing for DJ inoculation can be defined through
      monitoring of the pH in the P. luminescens culture.

PMID- 14727091
TI  - Inhibition of matrix metalloproteinase-2 activity by siderophores of Pseudomonas
      species.
AB  - To obtain a novel matrix metalloproteinase (MMP) inhibitor produced by bacteria,
      we have focused on the chelating activity of siderophores. Several siderophore
      producing bacteria were isolated from soil using chrome azurol S agar plates and
      then the effect of siderophores on MMP-2 activity was assayed by gelatin
      zymography. The results showed that partially purified siderophores from ten
      isolated strains inhibited MMP-2 activity. Among these strains, two were non
      fluorescent and eight were fluorescent Pseudomonas species. From these eight
      strains, pyoverdine-type siderophores were detected. The Zn(2+)-chelating
      activity of these siderophores correlated with the inhibition of MMP-2 activity.
      Therefore, it is considered that siderophores such as pyoverdines inhibit MMP-2
      activity by chelating Zn(2+) on the active site of MMP-2.

PMID- 14727092
TI  - CYP175A1 from Thermus thermophilus HB27, the first beta-carotene hydroxylase of
      the P450 superfamily.
AB  - The biological function of thermostable P450 monooxygenase CYP175A1 from Thermus
      thermophilus HB27 was studied by functional complementation in Escherichia coli.
      The gene product of CYP175A1 added hydroxyl groups to both beta rings of beta
      carotene to form zeaxanthin (beta,beta-carotene-3,3'-diol) in E. coli, which
      produces beta-carotene due to the Erwinia uredovora carotenoid biosynthesis
      genes. In addition, spectroscopic methods revealed that E. coli carrying CYP175A1
      and the cDNA of the Haematococcus pluvialis carotene ketolase was able to
      synthesise hydroxyechinenone. The predicted amino acid sequence of the enzyme
      from T. thermophilus does not show substantial similarity with other known beta
      carotene hydroxylases, but 41% with the cytochrome P450 monooxygenase from
      Bacillus megaterium (CYP102A1, P450 BM3). It is concluded that CYP175 A1
      represents a new type of beta-carotene hydroxylase of the P450 superfamily.

PMID- 14727093
TI  - Molecular and physiological characterisation of a 3-phytase from soil bacterium
      Klebsiella sp. ASR1.
AB  - Klebsiella sp. strain ASR1 isolated from an Indonesian rice field is able to
      hydrolyse myo-inositol hexakis phosphate (phytate). The phytase protein was
      purified and characterised as a 42 kDa protein accepting phytate, NADP and sugar
      phosphates as substrates. The corresponding gene (phyK) was cloned from
      chromosomal DNA using a combined approach of protein and genome analysis, and
      expressed in Escherichia coli. The recombinant enzyme was identified as a 3
      phytase yielding myo-inositol monophosphate, Ins(2)P, as the final product of
      enzymatic phytate hydrolysis. Based on its amino acid sequence, PhyK appears to
      be a member of a hitherto unknown subfamily of histidine acid phytate-degrading
      enzymes with the active site RHGXRXP and HD sequence motifs, and is different
      from other general phosphatases and phytases. Due to its ability to degrade
      sodium phytate to the mono phosphate ester, the phyK gene product is an
      interesting candidate for industrial and agricultural applications to make
      phytate phosphorous available for plant and animal nutrition.

PMID- 14727094
TI  - Steady-state and transient-state performance of a biotrickling filter treating
      chlorobenzene-containing waste gas.
AB  - Biotrickling filter (BTF) technology was applied for the treatment of waste gas
      containing a mixture of chlorobenzene and 1,2-dichlorobenzene. An adapted
      microbial community was immobilised on a structured packing material. The
      strategy followed was to reach high removal efficiencies at initially low mass
      loading rates followed by an increase of the latter. This procedure was
      successful and resulted in a short start-up period of only 2 weeks. A 3-month
      operation under steady-state conditions showed good performance, with >95%
      removal efficiency at a mass loading rate of 1,800 g m(-3) day(-1). Dimensionless
      concentration profiles showed that the chlorobenzenes were simultaneously
      degraded. Low dissolved organic carbon of 15 mg l(-1) and stoichiometric chloride
      concentrations in the trickling liquid indicated complete mineralisation of the
      pollutant. Transient-state experiments with five times higher mass loading rates
      caused a decrease in the removal efficiency that recovered rapidly once the mass
      loading rate returned to its original steady-state level. A progressive increase
      of the mass loading rate in a long-term performance experiment showed that the
      removal efficiency could be kept stable between 95 and 99% at loads of up to
      5,200 g m(-3) day(-1) over several days. Above this mass loading rate, the
      elimination capacity did not increase any further. These results demonstrated
      that with a well-adapted inoculum and optimal operation parameters, a BTF system
      with excellent performance and stability that efficiently removes a mixture of
      chlorobenzene vapours from air can be obtained.

PMID- 14727095
TI  - Effect of pH on Lactobacillus fermentum growth, raffinose removal, alpha
      galactosidase activity and fermentation products.
AB  - In this study, the behaviour of Lactobacillus fermentum CRL 722 and CRL 251 were
      evaluated under different pH conditions (pH 6.0, 5.5, 5.0, 4.5) and without pH
      control. Growth was similar under all conditions assayed except at pH 4.5. These
      microorganisms were able to eliminate raffinose, a nondigestible alpha
      oligosaccharide (NDO) found in soy products, showing a consumption rate of 0.25 g
      l(-1) h(-1) (pH 6.0-5.0). The removal of raffinose was due to the high alpha
      galactosidase (alpha-gal) activities of these lactic acid bacteria, which was
      highest at pH 5.5 (5.0 U/ml). The yield of organic acids produced during
      raffinose consumption was also highest at this pH. The results of this study will
      allow selection of the optimum growth conditions of L. fermentum with elevated
      levels of alpha-gal to be used in the reduction of NDO in soy products when used
      as starter cultures.

PMID- 14727096
TI  - Biosynthesis of deoxyaminosugars in antibiotic-producing bacteria.
AB  - Deoxyaminosugars comprise an important class of deoxysugars synthesized by a
      variety of different microorganisms; they can be structural components of
      lipopolysaccharides, extracellular polysaccharides, and secondary metabolites
      such as antibiotics. Genes involved in the biosynthesis of the deoxyaminosugars
      are often clustered and are located in the vicinity of other genes required for
      the synthesis of the final compound. Most of the gene clusters for aminosugar
      biosynthesis have common features, as they contain genes encoding dehydratases,
      isomerases, aminotransferases, methyltransferases, and glycosyltransferases. In
      the present mini-review, the proposed biosynthetic pathways for deoxyaminosugar
      components of both macrolide and non-macrolide antibiotics are highlighted. The
      possibilities for genetic manipulations of the deoxyaminosugar biosynthetic
      pathways aimed at production of novel secondary metabolites are discussed.

PMID- 14727097
TI  - Analysis of genomic and expressed major histocompatibility class Ia and class II
      genes in a hexaploid Lake Tana African 'large' barb individual (Barbus
      intermedius).
AB  - Expression of too many co-dominant major histocompatibility complex (MHC) alleles
      is thought to be detrimental to proper functioning of the immune system.
      Polyploidy of the genome will increase the number of expressed MHC genes unless
      they are prone to a silencing mechanism. In polyploid Xenopus species, the number
      of MHC class I and II genes has been physically reduced, as it does not increase
      with higher ploidy genomes. In the zebrafish some class II B loci have been
      silenced, as only two genomically bona fide loci, DAA/DAB and DEA/DEB, have been
      described. Earlier studies indicated a reduction in the number of genomic and
      expressed class II MHC genes in a hexaploid African 'large' barb. This prompted
      us to study the number of MHC genes present in the genome of an African 'large'
      barb individual (Barbus intermedius) in relation to those expressed, adopting the
      following strategy. Full-length cDNA sequences were generated from mRNA and
      compared with partial genomic class Ia and II sequences generated by PCR using
      the same primer set. In addition, we performed Southern hybridizations to obtain
      a verification of the number of class I and II B genes. Our study revealed three
      beta2-microglobulin, five class Ia, four class II A, and four class II B genes at
      the genomic level, which were shown to be expressed in the hexaploid barb
      individual. The class Ia and class II data indicate that the ploidy status does
      not correlate with the presence and expression of these MHC genes.

PMID- 14727098
TI  - Role of ligand-gated ion channels in the swimming behaviour of Xenopus tadpoles:
      experimental data and modelling experiments.
AB  - The swimming behaviour of lower vertebrates has been used as a model to study the
      function of simple neuronal circuits. Good examples are the lamprey and the
      Xenopus tadpole. In these two cases, glutamate-activated NMDA receptors are
      involved, and the relative importance of the NMDA and non-NMDA receptors as well
      as the involvement of other ion channels has been studied using a combination of
      electrophysiological recordings and modelling experiments, but little attention
      had been paid to their evolution during development. In the present experiments,
      which have been performed on Xenopus embryos from stages 31 to 42, we have probed
      the relative importance of the two categories of receptors using selective
      blockers [respectively dl-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX)]. The sensitivity of the swimming behaviour to
      APV was found to increase during development and that to CNQX to decrease.
      Furthermore, it has been observed that the spike activity recorded from the
      ventral roots is more complex in late embryonic stages that in early embryos.
      These modifications are associated with changes of the neuronal circuit, some of
      which correspond to a lengthening of the axon and an increased complexity of the
      dendritic tree of the motoneurons. We have incorporated these modifications in a
      simplified model of the central pattern generator built with Neuron software. The
      results indicate that at least part of the observed changes can be associated
      with changes in the length of the dendrites and axons.

PMID- 14727099
TI  - Risk factors for neo-aortic root enlargement and aortic regurgitation following
      arterial switch operation.
AB  - The objectives of this study were to evaluate changes in dimension of the neo
      aortic annulus, aortic root, and aortic anastomosis following arterial switch
      operation (ASO) and to identify risk factors for developing abnormal neo-aortic
      root enlargement and aortic regurgitation (AR). Prior studies report development
      of neo-aortic root dilatation and AR in a small subset of patients after ASO.
      Predisposing factors for neo-aortic root dilatation and development of
      moderate/severe AR are poorly understood. We performed a retrospective review of
      all patients with d-transposition of the great arteries (d-TGA) or double-outlet
      right ventricle with subpulmonary ventricular septal defect (VSD) who underwent
      ASO from May 1986 to January 2001. Serial echocardiograms were reviewed to
      measure neo-aortic annulus, root, and anastomosis diameter (z scores) and to
      determine progression of AR. Potential risk factors were assessed for developing
      neo-aortic root enlargement and AR. There were 119 patients (44 female and 75
      male): 73 patients had simple d-TGA, 36 had d-TGA with ventricular septal defect,
      and 10 had a Taussig-Bing heart. The median duration of follow-up was 65 months
      (range, 12-180). The median neo-aortic root (z = 0.55+/-2.2; p < 0.01) and aortic
      annulus dimensions (z = 1.57+/-1.75; p < 0.01) were significantly increased over
      the study period. Aortic anastomosis diameter correlated with growth of the
      ascending aorta (z = 0.55+/-1.24). Development of severe neo-aortic root
      enlargement was associated with prior pulmonary artery (PA) banding (p < 0.01),
      the presence of a VSD (p = 0.03), and Taussig-Bing anatomy (p < 0.01) but was
      independent of coronary arterial anatomy, coronary arterial transfer technique,
      or associated lesions (p > 0.05). At latest follow-up, there was no or trivial AR
      in 88 patients, mild AR in 29 patients, and moderate to severe AR in 3 patients.
      Risk factors for developing mild or worse AR included severe or rapid neo-aortic
      root dilatation (p < 0.01). Only 3 patients required surgical intervention for
      AR. Despite the significant prevalence of neo-aortic root enlargement at
      intermediate follow-up after ASO, there is a low incidence of significant AR.
      Prior PA banding, the presence of VSD, and Taussig-Bing anatomy are risk factors
      for severe root enlargement. Surgical intervention for AR was rare (2%), however,
      serial surveillance of such patients is vital to monitor for neo-aortic root
      enlargement and potential aortic valve dysfunction.

PMID- 14727100
TI  - Association of clinical characteristics of unexplained syncope with the outcome
      of head-up tilt tests in children.
AB  - The aim of this study was to clarify the association of clinical characteristics
      of unexplained syncope with the outcome of the head-up tilt test (HUT) in
      children. A total of 47 patients with unexplained syncope were classified into
      two groups according to their outcomes of HUT: the positive response group and
      the negative response group. We reviewed their clinical data as well as the
      results of HUT and analyzed them with logistic regression method. The results
      showed that the incidence of positive responses to HUT was higher in girls than
      in boys (8/22 vs 10/7, p < 0.05). Compared with fainted children younger than 12
      years of age, 12- to 16-year-old adolescents with unexplained syncope had a high
      positive outcome of HUT (30 vs 72.9%, p < 0.05). Compared with fainted children
      with negative response of HUT, children with positive response to HUT often had
      syncope in special circumstances (e.g., prolonged standing, anxiety and fright,
      and morning exercise), and they often had prodrome, such as pallor,
      lightheadedness, and nausea (28/30 vs 8/17, p < 0.05). However, the number and
      duration of syncopal spells did not relate to the positive responses to HUT. The
      logistic regression analysis showed that three factors significantly influenced
      the outcome of HUT: predisposing factors of syncope, prodrome of syncope, and age
      (p < 0.05; OR = 32.9434, 17.7281, and 2.7842, respectively). Hence, if pubertal
      girls with unexplained syncope had clear predisposing factors and prodromes, they
      were likely to have positive responses to HUT, and they were likely to be
      clinically considered as having vasovagal syncope.

PMID- 14727101
TI  - Heart rate variability in children with Fontan circulation.
AB  - Heart rate variability (HRV) can be used to study cardiovascular autonomic
      control. This study examines HRV in children with Fontan circulation and its
      change over time. Thirty-four children in two groups were examined. Group A
      consisted of 10 patients who had undergone total cavopulmonary connection. Group
      B consisted of 24 healthy children/adolescents matched for gender, height, and
      weight. To analyze HRV parameters, all examinations included echocardiography and
      24-hour ambulatory electrocardiogram. Comparing all patients and controls, there
      were no significant differences in HRV parameters. Analyzing subgroups of
      patients younger than 10 years old, two of the HRV parameters were significantly
      different compared to controls. For the group of patients older than 10 years,
      eight of the HRV parameters were significantly reduced. Most significant
      differences were found regarding low-frequency range (p < 0.008) and high
      frequency range p < 0.008. This study confirms the finding of earlier studies
      that patients with Fontan circulation have a reduced HRV, and our findings
      indicate that there is a progressive reduction of HRV over time.

PMID- 14727104
TI  - Prevention of shock wave-induced renal oxidative stress by melatonin: an
      experimental study.
AB  - Our aim was to evaluate the effects of the potent endogenous free radical
      scavenger melatonin on extracorporeal-shock-wave lithotripsy (ESWL) induced renal
      impairment. The study was performed using 30 rabbits which were divided into two
      groups. Both groups were exposed to 3,000 shock waves at 18 Kv. The animals in
      the first group were treated with melatonin for 8 days. Controls and melatonin
      treated rabbits were killed a week after ESWL. MDA, uric acid and white cell
      counts were used as markers of oxidative stress. The mean levels of uric acid and
      white cell counts were significantly lower in the melatonin treated group than in
      the controls. The mean level of MDA was also significantly lower in the melatonin
      treated group compared to the controls. Our results show that melatonin may
      exhibit a protective effect on free radical mediated oxidative damage induced by
      ESWL in rabbit kidney.

PMID- 14727105
TI  - Hematopoietic stem cell transplantation: more than just hematopoietic?
AB  - A wealth of evidence has surfaced in the last three years to challenge age-old
      notions of stem cell compartments in mammalian adult tissues. It was only
      recently realised that large cellular infusions in clinical practice might
      contain stem cells with flexible fate potential. This review discusses the
      current status of the occurence of epithelial chimerism after hematopoietic cell
      transplantation and presents existing data on detection methodology,
      characteristics, underlying mechanisms, physiological implications and clinical
      significance.

PMID- 14727106
TI  - Lack of neuroprotection by an ACTH (4-9) analogue. A randomized trial in patients
      treated with vincristine for Hodgkin's or non-Hodgkin's lymphoma.
AB  - PURPOSE: This randomized, double-blind, placebo-controlled study evaluates the
      effect of the corticotropin (4-9) analogue Org 2766 on the neuropathy-free
      interval in patients receiving vincristine (VCR) containing chemotherapy for
      Hodgkin's or non-Hodgkin's lymphoma. PATIENTS AND METHODS: In a longitudinal
      design, 150 patients were evaluated by interview, neurological examination, and
      neurophysiological techniques. Patients with an expected cumulative VCR dose of
      at least 8 mg received a single dose of Org 2766 or placebo before and after each
      intravenous VCR injection and 3-4 weeks after cessation of VCR. The final patient
      assessment was performed 1 month after discontinuation of study medication. The
      neuropathy-free interval as the major end point of this study was defined as the
      first occurrence of bilateral paresthesias and expressed as the administered
      cumulative VCR dose. This bi-center study represents the largest cohort of
      patients monitored for the effect of an ACTH-analogue on VCR neurotoxicity.
      RESULTS: A total of 147 patients were included in the final analysis. No
      significant differences were observed between the placebo and actively treated
      group for the major and secondary endpoints. CONCLUSION: Contrary to a single
      previous pilot study in patients receiving VCR-based chemotherapy, in our study
      the ACTH (4-9) analogue Org 2766 did not provide protection from VCR-induced
      neuropathy.

PMID- 14727107
TI  - Keratin immunohistochemistry in renal cell carcinoma subtypes and renal
      oncocytomas: a systematic analysis of 233 tumors.
AB  - Keratin immunohistochemistry represents a widely applied differential diagnostic
      tool in surgical pathology. To investigate the value of keratin subtyping for the
      diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we
      performed a detailed immunohistochemical study, applying 22 different monoclonal
      keratin antibodies on a large series of 233 renal tumors [125 conventional, 22
      chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66
      oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7,
      8, 18, and 19 was present in all tumor entities, albeit in varying quantities.
      With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct
      perinuclear and punctate dot-like pattern, which was not observed in renal cancer
      specimens. The only tumors showing immunoreactivity for keratin 20 were two type
      2 papillary cancers. All other monospecific keratin antibodies yielded
      consistently negative results. Overall, in contrast to some recent publications,
      keratin subtyping generally appeared to be of additional value only for the
      differentiation of renal epithelial tumors. Hence, with respect to differential
      diagnostic value, Hale's colloidal iron stain and vimentin immunostaining are
      still the most useful tools in renal tumor pathology.

PMID- 14727108
TI  - An enhancer-trap LacZ transgene reveals a distinct expression pattern of Kinesin
      family 26B in mouse embryos.
AB  - The enhancer-trap system is a useful tool to uncover genes that exhibit a unique
      tissue-specific expression. Here, we established a transgenic mouse line in which
      the reporter gene LacZ was specifically expressed in the developing limbs and
      face in the embryo. To identify the endogenous genes that are controlled by the
      limb- and face-specific enhancers, we pinpointed the integration site of the
      transgene, and analyzed the expression pattern of the genes that were located
      near the integration site. We found that the gene encoding KIF26B, a member of
      the kinesin superfamily, was preferentially expressed in the limb buds, face, and
      somite derivatives. Moreover, while a 7.5-kb mRNA was the major Kif26B transcript
      in the embryo, it was absent in many adult tissues. These results imply that
      KIF26B may play a role in embryogenesis, specifically in the development of
      limbs, face, and somites.

PMID- 14727109
TI  - A Dickkopf- 3-related gene is expressed in differentiating nematocytes in the
      basal metazoan Hydra.
AB  - In vertebrate development the Dickkopf protein family carries out multiple
      functions and is represented by at least four different genes with distinct
      biological activities. In invertebrates such as Drosophila and Caenorhabditis,
      Dickkopf genes have so far not been identified. Here we describe the
      identification and characterization of a Dickkopf gene with a deduced amino acid
      sequence closely related to that of chicken Dkk-3 in the basal metazoan Hydra.
      HyDkk-3 appears to be the only Dickkopf gene in Hydra. The gene is expressed in
      the gastric region in nematocytes at a late differentiation stage. In silico
      searches of EST and genome databases indicated the absence of Dkk genes from the
      protostomes Drosophila and Caenorhabditis, whereas within the deuterostomes, a
      Dkk-3 gene could be identified in the genome of the urochordate Ciona
      intestinalis. The results indicate that at an early stage of evolution of
      multicellularity Dickkopf proteins have already played important roles as
      developmental signals. They also suggest that vertebrate Dkk-1, 2 and 4 may have
      originated from a common ancestor gene of Dkk-3.

PMID- 14727111
TI  - Characterization of the genes for two soybean aspartic proteinases and analysis
      of their different tissue-dependent expression.
AB  - We isolated and characterized two cDNAs for aspartic proteinases (APs; EC 3.4.23)
      in soybean [Glycine max (L.) Merr.]. The encoded enzymes, soyAP1 and soyAP2,
      share 55% amino acid sequence identity. Northern analysis demonstrated that
      soyAP1 is expressed specifically in seeds, especially in dry seeds, while the
      expression of soyAP2 takes place in various tissues such as roots, stems, leaves
      and flowers, but not in dry seeds. SoyAP1 is highly expressed even at an early
      stage of germination, with a subsequent decrease in expression intensity. In
      contrast, the soyAP2 mRNA level increases 48 h after imbibition. To elucidate the
      physiological functions of soyAPs, we investigated the localization of soyAP
      expression in seeds germinating for 48 h at 25 degrees C. SoyAP1 shows cell-type
      specific expression in sieve tube cells of the hypocotyl. At the root tip, soyAP1
      is expressed in immature tracheary elements and sieve tube cells, and its
      expression pattern changes with distance from the tip; strong signals observed
      throughout phloem converge gradually to sieve tube cells, whereas those observed
      in tracheary elements disappear while the elements are still immature. On the
      other hand, soyAP2 signals were detected broadly in the boundary region between
      the cortex and the central cylinder. These results suggest that soyAP1 and soyAP2
      are functionally different from each other.

PMID- 14727112
TI  - Biochemical and immunological characterization of pea nuclear intermediate
      filament proteins.
AB  - In immunoblot assays, at least three putative nuclear intermediate filament (NIF)
      proteins were detected in nuclear envelope-matrix (NEM) and lamin (L1) fractions
      of nuclei from plumules of dark-grown pea (Pisum sativum L.) seedlings. These NIF
      proteins had apparent molecular masses of ca. 65, 60, and 54 kDa (also referred
      to as p65, p60, and p54), and appeared as multiple isoelectric forms, with pIs
      ranging from ca. 4.8 to 6.0. Polyclonal and monoclonal antibodies were raised to
      the 65-kDa NIF protein bands excised from gels after electrophoresis. These anti
      pea antibodies were specifically cross-reactive with the pea nuclear p65, p60,
      and p54 proteins and also with chicken lamins. Sequence alignment of peptide
      fragments obtained from the 65- and 60-kDa pea NIF proteins showed similarity
      with animal intermediate filament proteins such as lamins and keratins and with
      certain plant proteins predicted to have long coiled-coil domains. These pea NIF
      proteins were further purified and enriched from the NEM fraction using methods
      similar to those used for isolating animal lamins. When negatively stained and
      viewed by transmission electron microscopy, the filaments in the pea lamin (L1)
      fraction appeared to be 6-12 nm in diameter. As assayed by immunofluorescence
      cytochemistry using a confocal laser-scanning microscope, fixed pea plumule cells
      displayed uniform as opposed to peripheral nuclear staining by several of the
      antibody preparations, both polyclonal and monoclonal. This report describes the
      biochemical and immunological properties of these pea NIF proteins.

PMID- 14727113
TI  - Light differentially regulates the expression of two members of the auxin-induced
      1-aminocyclopropane-1-carboxylate synthase gene family in mung bean (Vigna
      radiata L.) seedlings.
AB  - Auxin induces the expression of the two ethylene-biosynthetic genes VR-ACS6 and
      VR-ACS7 in etiolated mung bean hypocotyls. However, while it also enhances VR
      ACS6 expression in light-grown tissues, it does not up-regulate VR-ACS7
      expression in these tissues. Here we show that transfer of 3-day-old etiolated
      seedlings into light quickly reduced the auxin-induced expression of both genes.
      However, while auxin-induced VR-ACS6 expression recovered after 24 h of light, VR
      ACS7 transcription continued to reduce and was almost completely absent at 36 h.
      Thus, light differentially modulates the expression of the auxin-inducible VR-ACS
      genes. In hormone-treated etiolated seedlings, VR-ACS7 was primarily induced in
      the rapidly elongating zones of hypocotyl and epicotyl tissues, while auxin
      induced VR-ACS6 mRNA was evenly distributed throughout the whole seedling. VR
      ACS7 promoter-driven beta-glucuronidase (GUS) activity in auxin-treated etiolated
      transgenic Arabidopsis seedlings was observed in the highly elongating zones of
      the hypocotyl. During de-etiolation, the GUS activity gradually declined to
      become confined to the uppermost region of hypocotyls. In situ mRNA localization
      studies showed that in etiolated mung bean hypocotyls, the auxin-dependent VR
      ACS7 transcript was predominantly present in the epidermis, which is the driving
      site for auxin-mediated elongation. Thus, it appears that the modulation by light
      of auxin-induced VR-ACS7 expression may correlate closely with the elongation
      growth response in early seedling development.

PMID- 14727114
TI  - Induced automaticity in isolated rat atrial cells by incorporation of a stretch
      activated conductance.
AB  - Stretch of the atrium and sympathetic activity have been implicated as substrates
      for atrial fibrillation. We investigate how a model of stretch in combination
      with sympathetic stimulation can induce automaticity in atrial cells. We adapted
      our coupling clamp circuit so that a model ionic current that represents stretch
      activated channels (SACs) was injected into an isolated rat atrial cell in real
      time. This current was calculated as ISAC= GSAC (Vm-ESAC), where GSAC and ESAC
      are the conductance and reversal potential of SACs and Vm is the cell's membrane
      potential. Repetitive automaticity was induced by a sufficiently large GSAC and
      this critical value of GSAC was decreased by exposure to isoproterenol. The
      critical value of GSAC decreased from 0.63+/-0.05 nS (mean+/-SE) in control to
      0.40+/-0.07 nS in isoproterenol (P<0.05). Additionally, after exposure to
      isoproterenol, automaticity continued after GSAC was no longer applied and was
      accompanied by delayed after-depolarizations. In three cells, repetitive
      automaticity could not be induced at any value of GSAC. Exposure to 10 nM
      isoproterenol converted these cells to cells with repetitive automaticity in
      response to GSAC. We conclude that automaticity can be induced in isolated rat
      atrial cells by application of a model of SACs. Exposure to isoproterenol
      enhances this effect.

PMID- 14727115
TI  - Epidermal growth factor receptor is activated by hyposmolarity and is an early
      signal modulating osmolyte efflux pathways in Swiss 3T3 fibroblasts.
AB  - Exposure of cultured Swiss 3T3 fibroblasts to 35% hyposmotic solution activated
      epidermal growth factor receptor (EGFR) phosphorylation to a greater extent than
      the ligand, EGF. Concanavalin A (Con A) and wheat-germ agglutinin (WGA) had the
      same effect. EGFR phosphorylation seems to be involved in the transduction
      signalling for hyposmotically induced taurine release, as suggested by the
      latter's reduction when EGFR phosphorylation was blocked by 50 microM AG213 or
      AG112 and, conversely, its potentiation by EGF (200 ng/ml). The relationship
      between hyposmotically induced taurine efflux and reduced osmolarity showed
      saturable kinetics, following a sigmoidal function. EGF shifted the relationship
      to the left, implying an increase in sensitivity to hyposmolarity. EGF increased
      taurine efflux only marginally under isosmotic conditions. EGF and agglutinins
      also potentiated the hyposmotically induced release of 86Rb but, in contrast to
      taurine, the efflux was unaffected by EGFR inhibition. EGF and agglutinins
      markedly increased 86Rb release under isosmotic conditions. The EGF-evoked
      isosmotic 86Rb release, together with the hyposmotic efflux, accounted fully for
      the observed potentiation by EGF, raising the possibility of an overlapping of
      these two effects, rather than a true potentiation. A link between EGFR,
      phosphatidylinositide-3-kinase (PI3K) and hyposmotically induced taurine (but not
      86Rb) release is suggested by the increase in PI3K activity elicited by
      hyposmolarity, which was fully prevented by EGFR inhibition, and by a marked
      reduction of hyposmotically induced taurine (but not 86Rb) release, by
      wortmannin. The present findings, together with results showing EGF activation of
      osmosensitive Cl- fluxes implicate EGFR as an important modulator of osmolyte
      efflux pathways.

PMID- 14727116
TI  - Hypotonic cell swelling stimulates permeability to cAMP in a rat colonic cell
      line.
AB  - This study characterized the membrane permeability to cAMP in a cell line derived
      from the rat colon (CC531(mdr+)) by comparison of fluxes of 3H-cAMP, 3H-8-bromo
      cAMP, 3H-taurine, 3H-adenosine and 3H-5'AMP under various experimental conditions
      including cell membrane depolarization and hypotonic cell swelling. Cell volume
      was modified by changing the osmolality and composition of the extracellular
      medium. Incubation in iso- and hypotonic KCl media induced graded increases in
      cell volume and stable activation of volume-sensitive channels that was reflected
      in an increased efflux of 3H-taurine. Incubation in hypotonic KCl solution also
      enhanced the efflux of 3H-8-Br-cAMP (a non-hydrolysable analogue of cAMP). Both
      the efflux of 3H-taurine and of 3H-8-Br-cAMP were inhibited by 5-nitro-2-(3
      phenylpropylamino)benzoate (NPPB, 100 microM) suggesting the involvement of
      volume-sensitive anion channels. To gain further insight into the route mediating
      cAMP permeability, the uptakes of 3H-cAMP, 3H-8-Br-cAMP and 3H-taurine were
      determined over short (5-min) periods. Uptakes of these substrates demonstrated
      close similarities: comparable increases were observed that correlated with the
      increases in cell volume in iso- and hypoosmotic KCl media; they were inhibited
      strongly by NPPB (100 microM) and metabolic inhibitors (deoxyglucose, 20 mM
      together with the mitochondrial uncoupler carbonylcyanide p
      (trifluoromethoxy)phenylhydrazone, FCCP, 10 microM) while barely reduced by
      dipyridamole (100 microM) and they were not affected by adenosine (1 mM). In
      contrast, the uptakes of 3H-adenosine and 3H-5'AMP had strikingly different
      properties; they were insensitive to cell swelling; barely inhibited by NPPB (100
      microM) and metabolic inhibitors (deoxyglucose and FCCP) while strongly reduced
      by dipyridamole (100 micro M). Unlike the uptakes of 3H-cAMP, 3H-8-Br-cAMP and 3H
      taurine, the uptakes of 3H-adenosine and 3H-5'AMP were reduced in Na(+)-free
      media, suggesting the presence in this cell line of two different adenosine
      carriers, one sodium-dependent and one sodium-independent. Taken together the
      present data show that in this rat colonic cell line, cAMP permeability is
      increased by cell swelling in hypotonic KCl medium and inhibited by NPPB and
      metabolic inhibitors. The similarity of these characteristics to those of taurine
      permeability suggests the involvement of a volume-sensitive anion pathway.

PMID- 14727117
TI  - Functional properties of skinned rabbit skeletal and cardiac muscle preparations
      containing alpha-cardiac myosin heavy chain.
AB  - Contractile properties of skinned muscle fibres from the masseter muscle and
      strips of heart atrium muscle from rabbits, both containing the alpha-cardiac
      myosin heavy chain isoform (alpha-cardiac MHC), were investigated and compared
      with those of other skeletal muscle fibre types. The stretch-induced delayed
      force increase (stretch activation) was investigated on maximally Ca(2+)
      activated skinned preparations as an index of the kinetic properties of the
      myosin heads of various MHC isoforms. Skeletal muscle fibres containing
      exclusively alpha-cardiac MHC (type alpha) and muscle strips of heart atrium
      showed specific kinetics of stretch activation intermediate between those of
      types IIA and I fibres. In agreement with available data the unloaded shortening
      velocity V(u) of type alpha fibres was also intermediate between that of types
      IIA and I fibres. Compared with skeletal muscle type alpha fibres, muscle strips
      of heart atrium exhibited significantly (P<0.001) faster kinetics of both stretch
      activation and V(u). We conclude that type alpha fibres have characteristic
      kinetic properties that fill the gap between the fast type II and the slow type I
      fibres, and the following order of velocity can be established:
      IIB>IID(X)>IIA>alpha>I.

PMID- 14727118
TI  - Activation kinetics of the slow afterhyperpolarization in hippocampal CA1
      neurons.
AB  - The activation of the slow afterhyperpolarization (sAHP) in CA1 neurons was
      studied using whole-cell recordings in the presence of inhibitors of the fast and
      medium-duration AHPs. The amplitude of the slow afterhyperpolarization current
      (IsAHP) increased as a function of duration and magnitude of the depolarizing
      voltage pulse reflecting graded increases in Ca(2+) influx through voltage
      dependent Ca(2+) channels. Therefore, the time constant for activation, tau(max),
      determined from a family of IsAHPs as a function of pulse duration, was voltage
      dependent decreasing several-fold within the range of -20 to 20 mV and was
      dependent on extracellular [Ca(2+)]. The IsAHP displayed a pronounced rising
      phase that was well fit by a single exponential with a time constant, tau(rise),
      that was invariant of pulse duration, voltage, IsAHP amplitude, or external
      [Ca(2+)] and was significantly slower than the tau(max). In current clamp, the
      magnitude of the sAHP increased with the number of evoked action potentials, yet
      tau(rise) of the sAHP was invariant of action potential number and was similar to
      the tau(rise) of the IsAHP recorded in voltage-clamp. The results suggest that
      there are two components to the development of the IsAHP, a rapid, voltage- and
      Ca(2+)-dependent step, the magnitude and rate of which reflects the voltage
      dependence of the Ca(2+) channels, that triggers a second rate-limiting, voltage
      independent process that dictates the slow IsAHP rise kinetics.

PMID- 14727119
TI  - New aspects and approaches in pre-operative planning of hip reconstruction: a
      computer simulation.
AB  - BACKGROUND: All computer-aided surgery technologies assume that the surgeon knows
      the best position for the implant components. However, there is indirect evidence
      that simple anatomical information may not be sufficient for the surgeon to
      decide size and position of the implant in a repeatable manner. METHOD: In the
      present study we estimated the variability in choosing the size and position of
      the components of a cementless total hip replacement (THR), using template-on
      radiograph as well as computed tomography (CT)-based computer-aided planning. In
      addition, using a computer model, we assessed the sensitivity to such variability
      of implant fitting, location of the joint centre, skeletal range of motion, and
      resting length of major hip muscles. Using templates, surgeons selected the size
      with variability up to 2.5 mm for the stem and up to 4 mm for the socket. A
      similar variability was also observed when the CT-based planning program was
      used. RESULTS: No major differences were found between surgeons. The standard
      deviation over repeated planning sessions of the selected position for each
      component, using the CT-based planning software, was found to be 3.9 mm and 8.9
      degrees . CONCLUSION: On the basis of the computer simulation, this variability
      did not affect the selected biomechanical parameters in a drastic way, although
      some differences were observed, especially in the lever arm of the hip muscles.

PMID- 14727120
TI  - Effect of the resection of the sciatic nerve on the Th1/Th2 balance in the
      synovia of the ankle joint of adjuvant arthritic rats.
AB  - Inflamed synovia of the ankle joint after 2-4 weeks of adjuvant injection
      receives dense sensory innervation. To study the role of sensory nerves on the
      local inflammation, the relative expression of T helper 1 and 2 lymphocyte (Th1
      and Th2) markers was investigated on both axotomized adjuvant arthritic (AA)
      rats, whose sciatic nerves were resected before adjuvant injection, and on sham
      operated ones. Immunohistochemical expressions of CXC chemokine receptor 3
      (CXCR3) and CC chemokine receptor 4 (CCR4) were examined and compared with those
      of Th1 cytokine (interferon-gamma, IFN-gamma), Th2 cytokine (interleukin-4, IL
      4), and anti-T cell antibody (W3/25). Double-positive cells for IFN-gamma/CXCR3
      and for IL-4/CCR4 were greater than 90% and greater than 95%, respectively. The
      reciprocal combinations, IL-4/CXCR3 and IFN-gamma/CCR4, however, yielded less
      than 10% and less than 5% of double-positive cells. CXCR3 and CCR4 thus appear to
      be available as markers for Th1/Th2 subsets in the synovia of AA rats. Using
      these markers, it became clear that the percentage of Th1 cells to total Th cells
      was higher than that of Th2 cells in axotomized AA rats at weeks 2-4, whereas in
      sham-operated AA rats, the percentage of Th1 cells to total Th cells was higher
      than that of Th2 cells at week 2 and the latter exceeded the former at week 4.
      Our observations strongly suggested the presence of the anti-inflammatory action
      of sensory nerves in rats with adjuvant arthritis.

PMID- 14727121
TI  - Negligent homicide by traumatic asphyxia.
AB  - We presented an unusual case of negligent homicide by thorax compression, which
      is the expanded concept of traumatic asphyxia. A 58-year-old man was restrained
      in the prone position by six prison officers. They were ordered by their
      superiors to continue restraining him for about 15 min and the victim died. At
      the forensic autopsy, typical findings of thorax compression with intramuscular
      hemorrhages on the back and multiple fractures of the ribs were observed. No
      evidence of neck compression/smothering or other fatal issues likely to occur by
      chest compression was found. The reconstruction of the scene corresponded exactly
      with the localization of the injuries found in the victim. This is the first case
      of death by pure thorax compression without other fatal factors during
      intentional restraint, in which the force causing the chest compression was
      distinctly determined by the autopsy and reconstruction.

PMID- 14727122
TI  - Evaluation of the Reid index in infants and cases of SIDS.
AB  - The Reid index is an instrument for the evaluation of chronic bronchitis. The
      thickness of the mucosa and of its gland layer are measured and the relationship
      is expressed as a gland/wall ratio. Specimens were obtained from 124 autopsies
      from the German National Study on SIDS (GeSID). The cases were divided into three
      groups: group 1 typical SIDS ( n=47), group 2 SIDS with signs of mild
      inflammation of the respiratory tract ( n=50) and group 3 unnatural death
      controls ( n=23). The Reid index was measured in sections from the trachea,
      bifurcation/main bronchi and bronchioli (staining HE and PAS). The Reid index was
      remarkably constant throughout the different levels of the respiratory tract
      (standard deviation range 0.06-0.10). A comparison of the three groups did not
      show statistically significant differences. Group 1: mean Reid index trachea
      0.37, bifurcation/main bronchi 0.38, bronchioli 0.39. Group 2: mean Reid index
      trachea 0.40, bifurcation/main bronchi 0.38, bronchioli 0.38. Group 3: mean Reid
      index trachea 0.39, bifurcation/main bronchi 0.38, bronchioli 0.41. It can be
      concluded that the dimensions of bronchial glands do not vary in cases of SIDS as
      compared to controls. This demonstrates that the Reid index has no significance
      in the vast majority of SIDS cases and that acute inflammation commonly does not
      produce an elevated Reid index. In addition, the Reid index was confirmed to be a
      valid instrument to study the respiratory tract including the trachea due to its
      stability and it was found that the Reid index is age-dependent: compared to
      adults, the ratios in infants were higher.

PMID- 14727123
TI  - Objective evaluation of the quality of substitution voices.
AB  - This paper describes our first attempts to develop a method for the objective
      assessment of quality in substitution voices. The objective analysis deals with
      acoustic parameters characterising short voice and speech samples like a sequence
      of isolated vowels, a sequence of VCV and CVCVCV syllables, a short sentence,
      etc. A database of 113 registrations from 68 patients (53 total laryngectomy
      patients with tracheo-esophageal speech, 14 total laryngectomy patients with
      esophageal speech and 5 patients with partial frontolateral laryngectomy) and 6
      registrations from healthy control persons was collected. Each registration
      consisted of seven speech utterances and was subjected to an acoustic analysis as
      well as to a perceptual evaluation, the latter involving eight parameters like
      "overall impression", "tonicity", etc. Since the goal of our work is to find out
      the best acoustical measurement for supporting perception and making it precise,
      it seemed logical to strive for a perceptually based acoustic analysis. We
      therefore performed the analysis by means of a peripheral auditory model with a
      built-in fundamental frequency (pitch) extractor. From the frame-level outputs (a
      frame is 10 ms) of the analyser, global objective parameters, such as (1) the
      percentage of voiced frames, (2) the average voicing evidence, (3) the voicing
      length distribution and (4) the fundamental frequency jitter, were computed for
      the different speech utterances. So as to reduce the parameter variability
      arising from the nature of the speech utterances (e.g., the presence of pauses in
      the signal, errors caused by the pitch extractor, etc.), the objective parameters
      were computed using non-standard averaging schemes involving energy weighting and
      frame selection. A statistical analysis of the objective parameters confirms that
      the quality of tracheo-esophageal speech is superior to that of esophageal
      speech, but inferior to that of normal speech and speech with the preservation of
      one vocal fold. Correlations between the objective parameters and the perceptual
      parameters are moderate.

PMID- 14727124
TI  - Preoperative diagnostic values of fine-needle cytology and MRI in parotid gland
      tumors.
AB  - The aim of this retrospective study was to assess and compare the diagnostic
      value of fine-needle cytology and MRI for the prediction of malignancy in parotid
      tumors. During an 11-year period, 148 patients underwent preoperative fine-needle
      aspiration cytology in our institution. Eighty-seven patients underwent a
      preoperative MRI study, and 54 had both MRI and cytology. The study compares
      results of cytology and MRI with histological reports. The sensitivity,
      specificity and accuracy for detecting malignant lesions were 87, 94 and 93%
      respectively for MRI, 81, 95 and 92% respectively for cytology and 100, 88 and
      91% respectively for both studies combined. Fine-needle cytology provided better
      information than MRI concerning precise histological diagnoses. Conversely, the
      proportion of non-diagnostic smears reached 10%. Fine-needle cytology and MRI are
      simple, well-tolerated diagnostic means with an impact on the management of
      salivary gland tumors. The associated anatomic information obtained by MRI
      imaging makes it the test of first choice in an optimal medical environment.

PMID- 14727125
TI  - Base of the tongue metastatic cancer from hepatocellular carcinoma: a case
      report.
AB  - Although hepatocellular carcinoma (HCC) is a common malignancy in Taiwan,
      metastasis to the head and neck area is extremely rare. In this report, we
      document a case of HCC metastasis to the base of the tongue. The patient involved
      had been treated for HCC with chemoembolization and radiotherapy 3 years prior to
      being diagnosed with tongue base metastasis. Symptoms of the metastasis included
      frequent oozing from the tongue base tumor. The patient died 3 months after a
      palliative resection of the tongue. To our knowledge, this is the first clinical
      presentation of HCC metastasis to the tongue base documented in the English
      language. We also believe that this particular case is important because we
      predict that the advancement in HCC treatment modalities will allow enough
      survival time in patients to cause occult extrahepatic metastatic lesion to
      develop into a field of clinical significance.

PMID- 14727126
TI  - Differences in recurrent COL7A1 mutations in dystrophic epidermolysis bullosa:
      ethnic-specific and worldwide recurrent mutations.
AB  - Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the gene
      encoding type VII collagen (COL7A1). Although most COL7A1 mutations are unique to
      individual families, small numbers of mutations are recurrent. The recurrent
      mutations R578X, 7786delG, and R2814X seem to be exclusive to a specific ethnic
      group, the British population. The mutations 5818delC, 6573+1G-->C, and E2857X
      are present only in individuals of Japanese ethnic origin. On the other hand, the
      mutations 425A-->G and G2043R have been found in several different ethnic groups.
      The purpose of this study was to clarify whether these recurrent mutations are
      also found in patients of other ethnic groups with DEB, mainly Asian patients. We
      demonstrated the absence of the recurrent mutations R578X, 7786delG, and R2814X
      in 42 non-British patients with DEB and detected the mutations 425A-->G in a
      French patient and G2043R in Japanese and Chinese patients with DEB. The
      mutations 5818delC, 6573+1G-->C, and E2857X were detected in 11 Japanese patients
      (13 alleles) with DEB. Our results confirm that R578X, 7786delG, and R2814X
      mutations are specifically limited to British patients, and the mutations
      5818delC, 6573+1G-->C, and E2857X are frequent in Japanese patients. On the other
      hand, the mutations 425A-->G and G2043R can be found in different ethnic groups.
      In conclusion, our results further support the notion that recurrent mutations
      can be classified into two types, ethnic-specific mutation and worldwide
      mutation.

PMID- 14727127
TI  - Difference in metallic wear distribution released from commercially pure titanium
      compared with stainless steel plates.
AB  - INTRODUCTION: Stainless steel and commercially pure titanium are widely used
      materials in orthopedic implants. However, it is still being controversially
      discussed whether there are significant differences in tissue reaction and
      metallic release, which should result in a recommendation for preferred use in
      clinical practice. MATERIALS AND METHODS: A comparative study was performed using
      14 stainless steel and 8 commercially pure titanium plates retrieved after a 12
      month implantation period. To avoid contamination of the tissue with the elements
      under investigation, surgical instruments made of zirconium dioxide were used.
      The tissue samples were analyzed histologically and by inductively coupled plasma
      atomic emission spectrometry (ICP-AES) for accumulation of the metals Fe, Cr, Mo,
      Ni, and Ti in the local tissues. Implant corrosion was determined by the use of
      scanning electron microscopy (SEM). RESULTS: With grades 2 or higher in 9
      implants, steel plates revealed a higher extent of corrosion in the SEM compared
      with titanium, where only one implant showed corrosion grade 2. Metal uptake of
      all measured ions (Fe, Cr, Mo, Ni) was significantly increased after stainless
      steel implantation, whereas titanium revealed only high concentrations for Ti.
      For the two implant materials, a different distribution of the accumulated metals
      was found by histological examination. Whereas specimens after steel implantation
      revealed a diffuse siderosis of connective tissue cells, those after titanium
      exhibited occasionally a focal siderosis due to implantation-associated bleeding.
      Neither titanium- nor stainless steel-loaded tissues revealed any signs of
      foreign-body reaction. CONCLUSION: We conclude from the increased release of
      toxic, allergic, and potentially carcinogenic ions adjacent to stainless steel
      that commercially pure Ti should be treated as the preferred material for
      osteosyntheses if a removal of the implant is not intended. However, neither
      material provoked a foreign-body reaction in the local tissues, thus cpTi cannot
      be recommend as the 'golden standard' for osteosynthesis material in general.

PMID- 14727128
TI  - Regulation of semaphorin 3A expression in neurons of the rat spinal cord and
      cerebral cortex after transection injury.
AB  - Semaphorin 3A (Sema3A) is a secreted repulsive axon guidance protein. It appears
      to play important roles in axon fasciculation, branching, neuronal migration, and
      tissue differentiation during embryonic development. In adults, Sema3A is
      expressed in spinal motoneurons and in some neurons in the brain. Here, we
      demonstrate changes in Sema3A expression in the spinal cord after complete
      transection and in the brain after spinal cord hemisection at the Th8 level in
      laboratory rats. Semi-quantitative reverse transcriptase-PCR analysis showed that
      the expression of Sema3A mRNA, which was present in the normal spinal cord,
      rapidly decreased after transection, reaching its lowest level 1 day after
      injury. Thereafter, Sema3A expression levels recovered and reached four-fifths of
      the normal level at 28 days. Double staining by in situ hybridization and
      fluorescence immunohistochemistry showed that Sema3A was expressed in NeuN
      positive neurons, but not in glia in the spinal cord. Sema3A expression was up
      regulated in the contralateral cerebral cortex and in the ipsilateral spinal
      trigeminal nucleus 1-3 days after spinal cord hemisection. It is likely that the
      up-regulation occurred in neurons whose descending fibers were transected. These
      results suggest that Sema3A is regulated differently in spinal motoneurons and
      brain neurons following axonal injury.

PMID- 14727129
TI  - The calcineurin signal transduction pathway is essential for successful muscle
      regeneration in mdx dystrophic mice.
AB  - Although mdx mice share the same genetic defect and lack dystrophin expression as
      in Duchenne muscular dystrophy (DMD), their limb muscles have a high regenerative
      capacity that ensures a more benign phenotype and essentially normal function.
      The cellular pathways responsible for this enhanced regenerative capacity are
      unknown. We tested the hypothesis that the calcineurin signal transduction
      pathway is essential for the successful regeneration following severe
      degeneration observed in the limb muscles of young mdx mice (2-4 weeks old) and
      that inhibition of this pathway using cyclosporine A (CsA) would exacerbate the
      dystrophic pathology. Eighteen-day-old mdx and C57BL/10 mice were treated with
      CsA for 16 days. CsA administration severely disrupted muscle regeneration in mdx
      mice, but had minimal effect in C57BL/10 mice. Muscles from CsA-treated mdx mice
      had fewer centrally nucleated fibers and extensive collagen, connective tissue,
      and mononuclear cell infiltration than muscles from vehicle-treated littermates.
      The deleterious effects of CsA on muscle morphology were accompanied by a 30-35%
      decrease in maximal force producing capacity. Taken together, these observations
      indicate that the calcineurin signal transduction pathway is a significant
      determinant of successful skeletal muscle regeneration in young mdx mice. Up
      regulating this pathway may have clinical significance for DMD.

PMID- 14727130
TI  - Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro.
AB  - BACKGROUND AND AIMS: Pancreatic stellate cells (PSCs) play a key role in the
      development of pancreatic fibrosis. The molecular mechanisms underlying their
      activation in response to profibrogenic mediators, however, are largely unknown.
      Extending previous studies on the transcriptional regulation of PSC activation,
      we have now focused on the involvement of activator protein (AP)-1. MATERIALS AND
      METHODS: Using cultured rat PSCs, phenotypic transition of PSCs towards activated
      myofibroblasts was monitored by an immunoblot analysis of alpha-smooth muscle
      actin (alpha-SMA) expression. Transcription factor activation profiles were
      studied by electrophoretic mobility shift assays. DNA synthesis in PSCs was
      assessed through the quantification of 5-bromo-2'-deoxyuridine incorporation.
      RESULTS: Activated AP-1 complexes were detectable already before high levels of
      alpha-SMA were expressed. Maximal DNA binding activity of AP-1, as well as of NF
      kappaB, was observed early in the course of PSC culture, while the strongest
      activation of STAT3 was observed much later. A detailed analysis of AP-1 complex
      composition revealed that phenotypic transition of PSCs towards myofibroblasts
      was accompanied by an increase of the JunD content relative to the one of JunB.
      Studies on the role of JunB and JunD in PSC activation indicated an inhibition of
      platelet-derived growth factor-induced DNA synthesis by antisense
      oligonucleotides to JunB but not JunD. CONCLUSIONS: The results of this study
      implicate AP-1 in PSC activation and suggest distinct roles of individual Jun
      proteins in the regulation of PSC function. In further studies, it should be
      analyzed whether signaling pathways involved in PSC activation might be suitable
      targets for antifibrotic therapies.

PMID- 14727132
TI  - Routine urine microscopy and culture in paediatric surgical outpatients: is it
      necessary?
AB  - Midstream urine culture has been the gold standard for diagnosing a urinary tract
      infection. But sample collection in children can be time-consuming and
      frustrating. In our department, a urine sample is routinely collected by the
      nursing staff prior to the outpatient consultation. We therefore reviewed our
      practice with respect to correlation with symptoms, change in management
      occurring as a result of the culture, and financial implications. Case notes of
      109 children attending paediatric nephrourology clinics over a three-month period
      were retrospectively reviewed. Data collected included underlying diagnosis,
      symptomatology, urine culture results at current and previous outpatient visits,
      and change in management that occurred as a direct result of the culture. A pure
      growth of >10(5 )colony-forming units/ml was considered to be a positive result.
      Of 783 urine samples, only 23 were positive in 15 patients, nine of which
      required change in management. All of these nine patients were symptomatic at or
      just preceding the clinic visit. None of the remaining patients in the group had
      symptoms of a urinary tract infection at the time of the outpatient visit. Change
      in management therefore occurred in 8.3% of patients, all symptomatic, based on
      the results of 1.1% of urine samples. At a cost of pound 3.00 per sample during
      working hours, the cost of processing 783 samples was pound 2349.00. We conclude
      that urine samples from paediatric surgical outpatients should not be sent
      routinely unless the patients are symptomatic or a change in management is
      anticipated. Other techniques to screen for urine samples needing culture may be
      considered.

PMID- 14727133
TI  - Auditory sensitivity and frequency selectivity in greater spear-nosed bats
      suggest specializations for acoustic communication.
AB  - We investigated the relationship between auditory sensitivity, frequency
      selectivity, and the vocal repertoire of greater spear-nosed bats ( Phyllostomus
      hastatus). P. hastatus commonly emit three types of vocalizations: group-specific
      foraging calls that range from 6 to 11 kHz, low amplitude echolocation calls that
      sweep from 80 to 40 kHz, and infant isolation calls from 15 to 100 kHz. To
      determine if hearing in P. hastatus is differentially sensitive or selective to
      frequencies in these calls, we determined absolute thresholds and masked
      thresholds using an operant conditioning procedure. Both absolute and masked
      thresholds were lowest at 15 kHz, which corresponds with the peak energy of
      isolation calls. Auditory and masked thresholds were higher at sound frequencies
      used for group-specific foraging calls and echolocation calls. Isolation calls
      meet the requirements of individual signatures and facilitate parent-offspring
      recognition. Many bat species produce isolation calls with peak energy between 10
      and 25 kHz, which corresponds with the frequency region of highest sensitivity in
      those species for which audiogram data are available. These findings suggest that
      selection for accurate offspring recognition exerts a strong influence on the
      sensory system of P. hastatus and likely on other species of group-living bats.

PMID- 14727131
TI  - Medical approaches and future options in chronic active ulcerative colitis.
AB  - BACKGROUND: Immunosuppressive therapy employing purine analogues is the
      therapeutic mainstay in patients with chronic active ulcerative colitis. However,
      despite therapeutic optimization according to thiopurine-methyltransferase
      activity or red blood cell 6-thioguanine levels, a substantial proportion of
      patients does not tolerate azathioprine or 6-mercaptopurine or relapses during
      this treatment. In the latter multiple therapeutic regimens comprising 6
      thioguanine, cyclosporin or tacrolimus, methotrexate, cyclophosphamide,
      infliximab, interferons, heparin, leukocyte apheresis, and various other regimens
      might be considered aiming at long-term remission. Many of these treatment forms
      have only been evaluated in small mostly uncontrolled trials. OBJECTIVE: In this
      review existing treatment modalities and future options for patients with chronic
      active ulcerative colitis will be discussed focusing on immunomodulating
      approaches.

PMID- 14727134
TI  - Sensing the effect of body load in legs: responses of tibial campaniform sensilla
      to forces applied to the thorax in freely standing cockroaches.
AB  - Sense organs in the legs that detect body weight are an important component in
      the regulation of posture and locomotion. We tested the abilities of tibial
      campaniform sensilla, receptors that can monitor forces in the cockroach leg, to
      encode variations in body load in freely standing animals. Small magnets were
      attached to the thorax and currents were applied to a coil below the substrate.
      Sensory and motor activities were monitored neurographically. The tibial sensilla
      could show vigorous discharges to changing forces when animals stood upon their
      legs and actively supported the body weight. Firing of individual afferents
      depended upon the orientation of the receptor's cuticular cap: proximal sensilla
      (oriented perpendicular to the leg axis) discharged to force increases while
      distal receptors (parallel to the leg) fired to decreasing forces. Proximal
      sensillum discharges were prolonged and could encode the level of load when
      increases were sustained. Firing of the trochanteral extensor motoneuron was also
      strongly modulated by changing load. In some postures, sensillum discharges
      paralleled changes in motor frequency consistent with a known interjoint reflex.
      These findings demonstrate that tibial campaniform sensilla can monitor the
      effects of body weight upon the legs and may aid in generating support of body
      load.

PMID- 14727135
TI  - Walking on a 'peg leg': extensor muscle activities and sensory feedback after
      distal leg denervation in cockroaches.
AB  - Previous studies in insects demonstrated that leg coordination changes following
      complete ablation of distal limb segments. However, normal coordination was
      restored when small 'peg leg' prostheses were attached to leg stumps to permit
      substrate contact. We have adapted this paradigm to preserve appropriate leg mass
      and inertia by severing all nerves and muscle tendons in the femur of the
      cockroach hind leg and converting the animal's own limb into a peg leg.
      Recordings of muscle activities and leg movements before and after denervation
      showed that: (1) the 'peg leg' is actively used in walking and regular bursts
      occur in motoneurons to leg extensor muscles; (2) driving of motoneuron activity
      is sufficient to produce 'fictive' bursting in a muscle whose tendon (apodeme) is
      cut in the ablation; and (3) similar motoneuron activities are found in walking
      on an oiled glass surface, when the effects of body weight and mechanical
      coupling are minimized. When distal segments were completely severed in these
      preparations, leg use and muscle bursting were disrupted but could be restored if
      the stumps were pressed against the substrate. These results support the
      hypothesis that feedback from receptors in proximal leg segments indicating
      forces allows for active leg use in walking.

PMID- 14727136
TI  - Prospective predictors of urinary continence after anatomical radical retropubic
      prostatectomy: a multivariate analysis.
AB  - The aim of this work was to evaluate variables that predict time to pad-free
      urinary continence after anatomical radical prostatectomy (ARP). Sixty
      consecutive prostate cancer patients who underwent ARP by one surgeon were
      studied. Pad-free urinary continence was prospectively determined by patient
      interviews and confirmed on physical examination and by the urinary domain of the
      Extended Prostate Inventory Composite (EPIC) Health Related Quality of Life
      questionnaire. A time-dependent Cox multivariate regression analysis was
      performed to determine which variables significantly correlated with time to pad
      free urinary continence. Increasing prostate size (cc), increasing prostate
      urethral length (cm) and surgical technique (wide excision of the neuro-vascular
      bundle) correlated with a significantly (P<0.05) prolonged time to achieve pad
      free urinary continence. In conclusion, prostate size and surgical technique were
      the most useful variables in predicting time to pad-free urinary continence after
      ARP.

PMID- 14727137
TI  - Functional annotation of mouse mutations in embryonic stem cells by use of
      expression profiling.
AB  - Expression profiling offers a potential high-throughput phenotype screen for
      mutant mouse embryonic stem (ES) cells. We have assessed the ability of
      expression arrays to distinguish among heterozygous mutant ES cell lines and to
      accurately reflect the normal function of the mutated genes. Two ES cell lines
      hemizygous for overlapping regions of mouse Chromosome (Chr) 5 differed
      substantially from the wildtype parental line and from each other. Expression
      differences included frequent downregulation of hemizygous genes and downstream
      effects on genes mapping to other chromosomes. Some genes were affected similarly
      in each deletion line, consistent with the overlap of the deletions. To determine
      whether such downstream effects reveal pathways impacted by a mutation, we
      examined ES cell lines heterozygous for mutations in either of two well
      characterized genes. A heterozygous mutation in the gene encoding the cell cycle
      regulator, cyclin D kinase 4 ( Cdk4), affected expression of many genes involved
      in cell growth and proliferation. A heterozygous mutation in the ATP binding
      cassette transporter family A, member 1 ( Abca1) gene, altered genes associated
      with lipid homeostasis, the cytoskeleton, and vesicle trafficking. Heterozygous
      Abca1 mutation had similar effects in liver, indicating that ES cell expression
      profile reflects changes in fundamental processes relevant to mutant gene
      function in multiple cell types.

PMID- 14727138
TI  - Dissection of multigenic obesity traits in congenic mouse strains.
AB  - Previous quantitative trait locus mapping (QTL) identified multigenic obesity
      (MOB) loci on mouse Chromosome (Chr) 2 that influence the interrelated phenotypes
      of obesity, insulin resistance, and dyslipidemia. To better localize and
      characterize the MOB locus, three congenic mouse strains were created.
      Overlapping genomic intervals from the lean CAST/Ei (CAST) strain were
      introgressed onto an obesity-susceptible C57BL/6 (BL6) background to create
      proximal (15 Mb-73 Mb), middle (63 Mb-165 Mb), and distal (83 Mb-182 Mb) congenic
      strains. The congenic strains showed differences in obesity, insulin, and lipid
      traits consistent with the original QTL analysis for the locus. Importantly,
      characterization of the MOB congenics localized the effects of genes that
      underlie obesity-related traits to an introgressed interval (73-83 Mb) unique to
      the middle MOB congenic. Conversely, significant differences between the lipid
      and insulin profiles of the middle and distal MOB congenics implicated the
      presence of at least two genes that underlie these traits. When fed an
      atherogenic diet, several traits associated with metabolic syndrome were observed
      in the distal MOB congenic, while alterations in plasma lipoproteins were
      observed in the middle MOB congenic strain.

PMID- 14727139
TI  - Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic
      hedgehog ( Shh).
AB  - Polarized expression of the Sonic hedgehog ( Shh) gene in the posterior
      mesenchyme is essential for pattern formation in the appendages of higher
      vertebrates, from teleost fins to tetrapod limb buds. We report on a sequence in
      intron 5 of the Lmbr1 gene, which resides approximately 1 Mb from the Shh coding
      region in the mouse genome and is highly conserved among teleost fishes and
      throughout the tetrapod lineage. Positional cloning revealed that two mouse
      mutations, Hx and M100081, characterized by mirror-image digit duplication and
      ectopic anterior Shh expression, have base substitutions in this sequence.
      Absence of the conserved sequence in limbless reptiles and amphibians and a cis-
      trans test using the Hx and Shh KO alleles suggest that the sequence is a cis
      acting regulator that controls the polarized expression of Shh.

PMID- 14727140
TI  - A novel Kruppel-Associated Box identified in a panel of mammalian zinc finger
      proteins.
AB  - Kruppel-related zinc finger proteins probably constitute the largest individual
      family of transcription factors in mammals. These proteins often carry a potent
      repressor domain called the Kruppel Associated Box (KRAB), which is known to
      effectively repress transcription through interaction with transcriptional
      intermediary factor 1beta (TIF1beta). Here we report the isolation and
      characterization of a novel human KRAB A zinc finger protein, HZF12. The gene
      encoding HZF12 is located on Chromosome (Chr) 19p13.11-p12, and a 4.4-kb
      transcript from this gene is expressed in a variety of adult and fetal tissues.
      Two additional, larger transcripts are expressed in testis only. Interestingly,
      the KRAB A domain of HZF12 is followed by a 21-amino acid domain, encoded by a
      separate exon. This domain, which we designate KRAB C, was also identified in
      more than 25 additional human, mouse, and rat KRAB zinc finger proteins. On the
      basis of results from a previous study, we conclude that this novel KRAB domain
      strengthens the interaction with TIF1beta, thereby improving the ability of these
      KRAB zinc finger proteins to recruit TIF1beta to specific sites.

PMID- 14727142
TI  - Comparative mapping of rat Iddm4 to segments on HSA7 and MMU6.
AB  - Iddm4 is one of several susceptibility genes that have been identified in the BB
      rat model of type 1 diabetes. The BB rat allele of this gene confers dominant
      predisposition to diabetes induction by immune perturbation in both the diabetes
      prone and the diabetes-resistant substrains, whereas the Wistar Furth (WF) allele
      confers resistance. We have positioned the gene in a 2.8-cM region on rat
      Chromosome (Chr) 4, proximal to Lyp/Ian4l1. We have produced a radiation hybrid
      map of the Iddm4-region that includes a number of rat genes with their mouse and
      human orthologs. We present a comparative map of the rat Iddm4 region in rat,
      human, and mouse, assigning the gene to a 6.3-Mb segment between PTN and ZYX at
      7q32 in the human genome, and to a 5.7-Mb segment between Ptn and Zyx in the
      mouse genome.

PMID- 14727141
TI  - Protocadherin X ( PCDHX) and Y ( PCDHY) genes; multiple mRNA isoforms encoding
      variant signal peptides and cytoplasmic domains.
AB  - The gene-poor, hominid-specific Yp11.2/Xq21.3 X-Y homology block encodes two
      members of the protocadherin group of cell surface molecules, PCDHX and PCDHY.
      These two genes, mainly expressed in brain, were known to be composed of at least
      six exons sharing 98.1% DNA identity. The genomic structure of PCDHX/ Y has been
      reanalyzed in detail, uncovering the existence of at least 11 more exons spanning
      more than 700 kb. Many of these exons located at the 5' and 3' ends of PCDHX/ Y
      undergo differential and alternative splicing. Seven of the exons have been found
      to use alternative splice sites. Most of these variants are expressed within the
      brain, although some isoforms exhibit a more ubiquitous distribution pattern.
      PCDHX/ Y transcription appears to be driven from two alternative promoters
      located usptream of exon 1 and exon 4.1. Assuming that the splicing events at the
      5' and 3' ends of these genes are independent of one another, potentially up to
      360 different mRNAs could be produced. The main impact on protein function is
      predicted to be in the efficiency of translation, post-translational processing
      within the cell, and structure of the cytoplasmic domain that may influence any
      role the genes have in signaling.

PMID- 14727143
TI  - A form of albinism in cattle is caused by a tyrosinase frameshift mutation.
AB  - We used PCR amplification of cDNA prepared from skin biopsies to determine the
      full-length protein-coding sequence of tyrosinase ( TYR) in cattle of several
      coat colors. An insertion of a cytosine was detected in an albino Braunvieh calf,
      which resulted in a frameshift which caused a premature stop codon at residue
      316. This insertion was found in the homozygous state in this calf and the
      genomic DNA of two related albino calves. All six parents of these calves were
      heterozygous for this insertion. However, an albino Holstein calf did not have
      this insertion, nor was any other mutation detected in the partial TYR sequence
      obtained from the genomic DNA available. Diagnostic genotyping tests were
      developed to detect this mutation in Braunvieh cattle.

PMID- 14727146
TI  - Screening for early lung cancer with low-dose spiral computed tomography: results
      of annual follow-up examinations in asymptomatic smokers.
AB  - The aim of this study was analysis of incidence results in a prospective one-arm
      feasibility study of lung cancer screening with low-radiation-dose spiral
      computed tomography in heavy smokers. Eight hundred seventeen smokers (> or =40
      years, > or =20 pack years of smoking history) underwent baseline low-dose CT.
      Biopsy was recommended in nodules >10 mm with CT morphology suggesting
      malignancy. In all other lesions follow-up with low-dose CT was recommended.
      Annual repeat CT was offered to all study participants. Six hundred sixty-eight
      (81.8%) of the 817 subjects underwent annual repeat CT with a total of 1735
      follow-up years. Follow-up of non-calcified nodules present at baseline CT
      demonstrated growth in 11 of 792 subjects. Biopsy was performed in 8 of 11
      growing nodules 7 of which represented lung cancer. Of 174 new nodules, 3
      represented lung cancer. The 10 screen-detected lung cancers were all non-small
      cell cancer (6 stage IA, 1 stage IB, 1 stage IIIA, 2 stage IV). Five symptom
      diagnosed cancers (2 small cell lung cancer: 1 limited disease, 1 extensive
      disease, 3 central/endobronchial non-small cell lung cancer, 2 stage IIIA, 1
      stage IIIB) were diagnosed because of symptoms in the 12-month interval between
      two annual CT scans. Incidence of lung cancer was lower than prevalence, screen
      detected cancers were smaller, and stage I was found in 70% (7 of 10) of screen
      detected tumors. Only 27% (4 of 15) of invasive procedures was performed for
      benign lesions; however, 33% (5 of 15) of all cancers diagnosed in the population
      were symptom-diagnosed cancers (3 central NSCLC, all stage III, 2 SCLC)
      demonstrating the limitations of CT screening.

PMID- 14727147
TI  - Carnocin KZ213 produced by Carnobacterium piscicola 213 is adsorbed onto cells
      during growth. Its biosynthesis is regulated by temperature, pH and medium
      composition.
AB  - Carnocin KZ213 is an antilisterial bacteriocin produced by Carnobacterium
      piscicola 213. The effects of pH and temperature were studied during batch
      fermentation in MRS* medium (modified MRS without ammonium citrate or sodium
      acetate). The optimal pH for growth is between 6 and 7. The maximum bacteriocin
      productivity in the supernatant occurs at pH 7. Operating at controlled pH
      increases the volumetric activity of the free bacteriocin by 8- to 16-fold,
      compared with uncontrolled pH. No bacteriocin production is observed below pH
      6.5. Temperature has a dramatic effect on carnocin KZ213 production. Growth is
      optimal at 25 degrees C and 30 degrees C, although no bacteriocin production is
      detected at 30 degrees C. Also, bacteriocin production is observed at 25 degrees
      C in MRS*, but not in complex APT broth, where growth is optimal. The presence of
      glucose as a carbon and/or energy source is important for carnocin KZ213
      synthesis. Hence, bacteriocin synthesis is regulated by temperature, carbon
      source and medium composition. Quantification studies of bacteriocin adsorbed
      onto producer cells show that the majority of the carnocin KZ213 secreted is
      adsorbed onto the producer cells during growth. Only 15% of the total bacteriocin
      produced is detected in the cell-free supernatant at the end of growth.

PMID- 14727148
TI  - Construction and analysis of a BAC library in the grass Brachypodium sylvaticum:
      its use as a tool to bridge the gap between rice and wheat in elucidating gene
      content.
AB  - A BAC library of 30,228 clones with an average insert size of 102 kb was
      constructed in the grass Brachypodium sylvaticum. Brachypodium has a simple
      genome, similar in size and repetitive DNA content to that of rice, and is more
      closely related than rice both to the major temperate cereals wheat and barley,
      and to the forage grasses. The library represents 6.6 genome equivalents,
      implying a 99.9% probability of recovering any specific sequence. The library was
      arrayed onto two high-density colony filters, which were screened with
      heterologous DNA probes from rice chromosome nine and from syntenous regions of
      wheat, barley, maize and oat. The construction of Brachypodium BAC contigs
      revealed that synteny between rice, wheat and Brachypodium was largely maintained
      over several regions of rice chromosome nine. This suggests that Brachypodium
      will be a useful tool in the elucidation of gene content in agronomically
      important cereal crops, complementing rice as a "grass genome model".

PMID- 14727150
TI  - Empiric oral monotherapy for hospitalized patients with community-acquired
      pneumonia: an idea whose time has come.

PMID- 14727149
TI  - Full-course oral levofloxacin for treatment of hospitalized patients with
      community-acquired pneumonia.
AB  - Most guidelines for the management of hospitalized patients with community
      acquired pneumonia (CAP) recommend commencing therapy with intravenous
      antibiotics, primarily because of concern about absorption of oral antibiotics in
      acutely ill patients. However, patients who respond are rapidly switched to oral
      therapy, which has been shown to reduce costs and to shorten the length of stay.
      The aim of the present study was to determine whether a full course of oral
      antibiotics is as efficacious and as safe as intravenous-to-oral sequential
      antibiotic therapy for the treatment of hospitalized, non-ICU patients with CAP.
      In an open-labelled, controlled study, 129 hospitalized patients with CAP were
      randomly assigned in a 2:1 ratio to receive either a full course of oral
      levofloxacin (500 mg q12 h) or an intravenous-to-oral sequential therapy
      consisting of intravenous ceftriaxone (2 g q24 h) with or without clarithromycin
      (500 mg q12 h) followed by an oral antibiotic (a beta-lactam agent in the
      majority of patients). The primary study endpoint was the resolution of CAP;
      secondary endpoints included length of stay and overall mortality. CAP resolved
      in 72 of 79 (91.1%) patients in the levofloxacin group and in 34 of 37 (91.9%)
      patients in the intravenous-to-oral sequential therapy group (difference, -0.8%,
      95%CI, -11.6-10.0). Median length of stay was 8 days (range, 2-74 days) in the
      levofloxacin group and 10 days (range, 3-29 days) in the intravenous-to-oral
      sequential therapy group ( P=0.28). Day 30 mortality rates were 1.3% (1 of 79)
      and 8.1% (3 of 37), respectively (difference, -6.8%, 95%CI, -16.0-2.3). Full
      course oral levofloxacin is as efficacious and as safe as standard intravenous-to
      oral sequential antibiotic therapy for the treatment of hospitalized patients
      with CAP.

PMID- 14727151
TI  - Severe myelitis following infection with Campylobacter enteritis.

PMID- 14727152
TI  - Analysis of sequence variability of the bovine prion protein gene (PRNP) in
      German cattle breeds.
AB  - Different alleles of the prion protein gene (PRNP) of human and sheep are known
      to be associated with varying susceptibilities to transmissible spongiform
      encephalopathies. However, no polymorphisms in the bovine PRNP gene with an
      effect on susceptibility to prion diseases have been identified to date. In this
      study we investigated such polymorphisms in German cattle; 48 healthy animals
      from six different German cattle breeds and 43 cattle with bovine spongiform
      encephalopathy (BSE) were analyzed. In contrast to previous studies, all three
      exons as well as the promoter region of the PRNP gene were investigated. Sequence
      variants in the bovine PRNP gene could have an impact on the amino acid sequence
      or the expression level of the prion protein and thus on susceptibility to BSE.
      We identified a total of 60 polymorphisms in the PRNP gene of German cattle. Of
      these 60 polymorphisms, 36 were newly identified, whereas 24 of these
      polymorphisms had been described previously. We did not detect any novel
      polymorphisms affecting the amino acid sequence of the prion protein. However, we
      identified a 23-bp insertion/deletion polymorphism in the putative PRNP promoter
      region that shows a significant association with BSE susceptibility in our
      animals.

PMID- 14727153
TI  - Catalog of 162 single nucleotide polymorphisms (SNPs) in a 4.7-kb region of the
      HLA-DP loci in southern Chinese ethnic groups.
AB  - HLA class-II proteins are cell-surface molecules that present antigens to T
      cells, and their expressional regulation is crucial to the immune reaction.
      Sequence variation at the regulatory region can directly affect the gene
      expression level. We cloned and sequenced a 4.7-kb region containing the
      regulatory region, exon1, and partial intron1 of both HLA-DPA1 and DPB1 genes in
      25 variable sequences from southern Chinese ethnic groups and got a high-density
      map of 162 single nucleotide polymorphisms (SNPs): seven in 5'-flanking regions,
      four in 5'-untranslated regions, and four in the coding regions. By comparing
      these data with SNPs in dbSNP database in the NCBI, 145 SNPs (89.5%) were novel.
      In addition, eight genetic variations of insertion-deletion polymorphisms
      (INDELs) were discovered within the 4.7-kb region. These high-resolution maps can
      be used as resources of markers for association studies of complex diseases,
      assessment of individuals' predisposition to diseases, and tailoring of
      therapies, as well as research markers for population genetics and evolution.

PMID- 14727154
TI  - LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for
      bone mineral density.
AB  - Osteoporosis is a multifactorial trait with low bone mineral density (BMD). We
      report results of an association study between BMD and nine candidate genes (
      TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a
      case-control study of osteoporosis. Samples for the former association study
      included 481 general Japanese women. Among the nine candidate genes examined,
      only LRP5 showed a significant association with BMD. We identified a strong
      linkage disequilibrium (LD) block within LRP5. Of five LPR5 single nucleotide
      polymorphisms (SNPs) that are located in the LD block, three gave relatively
      significant results: Women with the C/C genotype at the c.2220C>T SNP site had
      higher adjusted BMD (AdjBMD) value compared to those with C/T and T/T (p=0.022);
      and likewise, G/G at IVS17-30G>A and C/C women at c.3989C>T showed higher AdjBMD
      than those with G/A or A/A (p=0.039) and with C/T or T/T ( p=0.053),
      respectively. The case-control study in another series of samples consisting of
      126 osteoporotic patients and 131 normal controls also gave a significant
      difference in allele frequency at c.2220C>T (kappa2=6.737, p=0.009). These
      results suggest that LRP5 is a BMD determinant and also contributes to a risk of
      osteoporosis.

PMID- 14727155
TI  - High heritability of bone size at the hip and spine in Chinese.
AB  - Bone size, an independent determinant of bone strength, is an important risk
      factor for osteoporotic fracture. In the present study, we investigated the
      magnitude of the genetic determination of bone size at the spine and hip and
      their genetic covariation (if any) in a population of Chinese residing in
      Shanghai City of P.R. China. The subjects were 50 healthy full-sib pairs of
      females, 188 mother-daughter pairs, and 128 husband-wife pairs selected from 401
      nuclear families. Bone size (centimeters squared) was measured at the spine and
      hip by dual-energy X-ray absorptiometry (DEXA). The narrow-sense heritabilities
      h2 (SE) of bone size at the spine and hip were 0.63 (0.14) and 0.45 (0.14)
      respectively when estimated by full-sib pairs, and 0.60 (0.07) and 0.69 (0.07)
      respectively when estimated by mother-daughter pairs. Marginally significant
      genetic correlation was observed between the spine and hip bone size. The
      significantly and moderately high h2 values for bone size demonstrated in this
      study warrant a subsequent genetic study to search for the genes or genomic
      regions underlying the phenotype in Chinese.

PMID- 14727156
TI  - Genetic variants in PCSK9 affect the cholesterol level in Japanese.
AB  - Mutations in the proprotein convertase subtilisin/kexin 9 ( PCSK9) gene have been
      reported in affected members of two families with autosomal dominant
      hypercholesterolemia. To investigate the effects of common variants in PCSK9 on
      the cholesterol level, we conducted an association study using a large cohort
      representing the general population in Japan (n=1,793). Direct sequencing in all
      of the exonic regions identified 21 polymorphisms. After consideration of linkage
      disequilibrium among these polymorphisms, we selected and genotyped nine
      polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V
      polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T,
      P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(
      161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in
      subjects with miocardial infarction (MI) (n=649) were not different from those in
      the control population. These results provide the first evidence that common
      variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and
      LDL-C levels in the general population in Japan.

PMID- 14727158
TI  - Predictors of cardiac morbidity and mortality in patients undergoing endovascular
      repair of the thoracic aorta.
AB  - The aim of this study was to determine predictors of cardiac morbidity and
      mortality in patients undergoing endovascular repair of the thoracic aorta. This
      was a retrospective cohort study that took place in a University-affiliated
      county hospital. Preoperative and intraoperative variables were collected from a
      consecutive series of patients who underwent repair of the thoracic aorta at our
      institution between 1998 and 2003. Perioperative complications and mortality were
      identified for each patient. Fifty-nine patients underwent endovascular repair of
      the thoracic aorta. The endografts were successfully deployed in 58 (98%)
      patients. Nine (15%) died perioperatively, 4 (7%) from cardiac causes. There were
      12 (20%) perioperative cardiac events. A history of myocardial infarction (MI)
      was the only preoperative risk factor that was predictive of a cardiac event (p =
      0.001). The cardiac event rate was 29% for patients who did not receive
      perioperative beta-blockade vs. 8% in patients who did (p = 0.04). Intraoperative
      predictors of MI were estimated blood loss (2480 cc vs. 680 cc, p = 0.01),
      intravenous (i.v.) fluids (2955 cc vs. 2010 cc, p =0.02), and length of operation
      (269 min vs. 178 min, p = 0.02). From these results we concluded that mortality
      associated with endovascular repair of thoracic aorta remains significant.
      Patients with a history of MI had a higher perioperative cardiac event rate.
      Intraoperative predictors of perioperative cardiac events included blood loss,
      i.v. fluid requirement, and length of operation. Perioperative beta-blockade is
      important in endovascular thoracic surgery as a protection against postoperative
      cardiac events.

PMID- 14727159
TI  - Acute aortic dissection presenting as rupture of the femoral artery.
AB  - A 44-year-old male with Marfan's disease presented acutely with severe chest and
      left groin pain. A pulsatile mass was present in the left groin and the left leg
      was pale and pulseless. CT imaging demonstrated the presence of a distal thoracic
      aortic dissection (AD) involving the left iliofemoral segment with extravasation
      of contrast into the left groin. The patient was treated with an urgent femoral
      femoral bypass, which repaired the femoral artery and restored perfusion to the
      left lower extremity. Whereas rupture of the aorta into the chest or pericardium
      is common, femoral artery rupture complicating AD has not been previously
      reported. This case illustrates the need for peripheral branch intervention when
      compromised by the dissection process including isolated iliofemoral segments,
      which are typically benign. Given frank femoral artery rupture, urgent surgical
      repair was required and resulted in a satisfactory outcome.

PMID- 14727160
TI  - Duodenocaval fistula: a late complication of retroperitoneal irradiation and vena
      cava replacement.
AB  - Duodenocaval fistula (DCF), an unusual pathology, is associated with a 40%
      mortality rate in the 36 patients previously reported. Although migrating or
      ingested foreign bodies, trauma, and peptic ulcer disease are often described
      etiologies, 11 patients have been described who developed DCF after resection of
      retroperitoneal tumors, 9 of whom also had postoperative radiotherapy. We report
      two patients who developed DCF after resection of retroperitoneal tumors followed
      by radiation therapy. The first patient, a 56-year-old female, presented with
      upper gastrointestinal hemorrhage requiring transfusion caused by a
      duodenoprosthetic caval fistula 7 years after successful resection of a
      retroperitoneal leiomyosarcoma and replacement of the inferior vena cava followed
      by radiation and chemotherapy. The second patient, a 37-year-old male who had
      previously undergone resection of a retroperitoneal sarcoma followed by external
      radiotherapy, developed massive upper and lower gastrointestinal bleeding
      secondary to a duodenocaval fistula. The etiology, diagnosis, and treatment of
      DCF are analyzed with an emphasis on DCF following resection and irradiation of
      retroperitoneal tumors. In most patients, "spontaneous" DCF have occurred as a
      late complication of high-dose radiation for carcinoma of the right kidney or
      retroperitoneal structures.

PMID- 14727161
TI  - Early experience with radiofrequency ablation of the greater saphenous vein.
AB  - Radiofrequency ablation of the greater saphenous vein (GSV) has been proposed as
      an alternative to conventional ligation and stripping in the treatment of
      varicose veins. We have reviewed our initial experience with this new technology
      in 28 procedures on 24 patients. Preoperative duplex scans confirmed venous
      valvular incompetence of the GSV in all patients. Intraoperative ultrasound was
      used to measure the depth of the GSV, to precisely place the radiofrequency
      catheter adjacent to the saphenofemoral junction, and to confirm the results of
      the ablative procedure. Occlusion of the GSV was seen on 96% of completion scans
      and in all patients within 1 week of the procedure. Duplex scans were available
      for 21 limbs at 3 months and for 3 at 1 year. Persistent occlusion was documented
      in all cases. No patient had paresthesias or thermal skin injury. Two patients
      had transient superficial thrombophlebitis around the knee in a treated segment
      of the GSV. One patient was found to have extension of an asymptomatic,
      nonocclusive thrombus into the common femoral vein on a routine scan 3 days after
      surgery. Postoperative patient questionnaires showed that 96% of respondents were
      very satisfied with the procedure. Radiofrequency ablation of the GSV appears to
      be a safe alternative to conventional stripping and ligation. Subjective
      assessment by the surgeons suggests an earlier return to work and active
      lifestyle compared to traditional extirpative techniques. Longer follow-up is
      required to establish the durability of the procedure.

PMID- 14727162
TI  - Superiority of autogenous arteriovenous hemodialysis access: maintenance of
      function with fewer secondary interventions.
AB  - The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF
      K/DOQI) guidelines have advocated autogenous arteriovenous fistulae as a primary
      procedure for hemodialysis access. This study compared the clinical outcomes
      between autogenous and prosthetic arteriovenous hemodialysis accesses,
      determining factors contributing to primary and secondary patency and function.
      Associated risk factors and number of interventions required to maintain
      secondary patency in each cohort were also assessed. A vascular database review
      of consecutive hemodialysis access procedures performed during a 36-month period
      (January 1999 to December 2001) at an academic institution was conducted. Life
      table and log-rank analyses were used to analyze patency rates. Univariate and
      multivariate analysis was used to analyze risk factor influence on patency and
      function. A total of 231 upper extremity arteriovenous access procedures were
      performed in 209 patients during this period. One hundred autogenous accesses
      were created in 100 patients, 68 being forearm Brescia-Cimino arteriovenous
      fistulae. A total of 131 prosthetic accesses (ePTFE) grafts were also placed
      during this period in 109 patients. The demographic profiles of both cohorts were
      similar. Primary patency at 1 and 2 years was 56% (CI 45-76%) and 39% (CI 28
      50%), respectively, in the autogenous group, and 36% (CI 26-45%) and 9% (CI 3
      14%), respectively, in the prosthetic group. Differences in secondary patency at
      1 year and 2 years were not significant (64% [CI 54-74%] and 53% [CI 42-65%] in
      the autogenous group vs. 65% [CI 55-73%] and 46% [CI 36-55%] in the prosthetic
      group). Secondary interventions were required in 87% of the prosthetic cohort
      (average 0.92 procedures/patient/year) and 57% of the autogenous cohort (average
      0.53 procedures/patient/year). Multivariate analysis of associated risk factors
      demonstrated no significant effects on either primary or secondary patency in
      both groups. Autogenous accesses have superior primary patency and maintain equal
      secondary patency with significantly fewer interventions. These data strongly
      support the NKF K/DOQI guidelines recommending creation of autogenous access
      whenever possible. These outcomes can provide significant health-care cost
      benefits when using an algorithm favoring primary creation of autogenous access
      for hemodialysis.

PMID- 14727163
TI  - Endovascular abdominal aortic aneurysm repair using the AneuRx stent graft:
      impact of excluding accessory renal arteries.
AB  - The aim of this study was to evaluate clinical sequelae of accessory renal artery
      exclusion during endo-AAA repair. Medical records and pre- and postoperative CT
      scans were reviewed from 114 AAA patients treated with the AneuRx stent graft
      between 1996-2001. Thirty-seven accessory renal arteries were identified in
      32/114 patients (28%) with 19/32 patients having infrarenally located accessory
      renal arteries. In group I (11 patients), the stent graft excluded 11 accessory
      renal arteries. In group II (8 patients), eight accessory renal arteries were not
      excluded. Average infrarenal neck length was 24.9 mm in group I vs. 30.7 mm in
      group II (p = 0.07). The average length of device seal was similar in both groups
      (19.4 vs. 18.5 mm, p = 0.67). There were no perioperative deaths, significant
      postoperative hypertension, rise in serum creatinine, or postoperative renal
      infarctions in either group. Three of eight patients (38%) in the non-excluded
      group developed type I proximal endoleaks whereas none in the excluded patient
      group did (p = 0.06). Accessory renal arteries may be safely excluded during
      endovascular AAA repair and may result in a more secure proximal device fixation.

PMID- 14727164
TI  - Essential techniques for intraoperative composite endograft (CEG) formation in
      the treatment of abdominal aortic aneurysm.
AB  - The development of an ideal aortic stent graft continues to progress. New devices
      and techniques are expanding the use of endovascular repair in the treatment of
      abdominal aortic aneurysms (AAA). We present data with intraoperative composite
      endograft (CEG) techniques evaluating immediate and short-term compatibility of
      components and patients outcome. Twenty-five of 66 patients (38%) received
      intraoperative CEGs for AAA treatment. A total of 50 components were used to
      treat type I endoleaks, prevent graft limb kinking or treat associated iliac
      aneurysm. Nine of the components were used to manage type I proximal endoleaks.
      Forty-one components were used at the iliac limb for distal type I endoleak,
      hostile iliac anatomy, or graft limb support or to treat an associated iliac
      aneurysm. Two patients were left with a type I endoleaks at the iliac attachment
      site on completion of graft placement. With a mean follow-up of 11 months. Two of
      25 patients had a type II endoleak at 6 months. One patient had type I endoleak
      at 1 year follow-up. CEGs are essential to treat endoleaks with a high technical
      success rate and expand the indications for treating infrarenal AAA. The
      component's short-term compatibility makes this method of stent graft placement
      safe.

PMID- 14727165
TI  - External beam ionizing radiation for inhibition of myointimal hyperplasia after
      dilatation and anastomoses: experimental models and results.
AB  - In recent years there has been intensive research on the use of ionizing
      radiation for inhibition of intimal hyperplasia (IH). Results have clearly
      established that beta ionizing radiation delivered from an endoluminal source
      after angioplasty inhibits intimal restenosis. This effect has been confirmed by
      recent multicenter clinical trials in patients undergoing coronary dilatation.
      The purpose of this study was to determine if gamma radiation therapy delivered
      superficially from an external source also reduced smooth muscle cell
      proliferation in two animals models-the first involving experimentally induced
      restenosis and the second involving anastomosis between a prosthesis and artery.
      Ultimately we hope to develop a therapeutic application for patients undergoing
      peripheral anastomoses, especially in the lower extremities. Two different animal
      models were used in this two-stage study. The first-stage rabbit model (model 1)
      involved balloon injury of the aorta to validate the dose effect of external beam
      irradiation. The second-stage porcine model (model 2) involved aortic bypass
      followed by external beam irradiation of the distal anastomosis site. In model 1
      a total of 56 rabbits were studied. They were divided into five groups including
      one control group in which external radiation was not applied after balloon
      injury and four test groups in which external radiation was applied in a single
      fraction on day 0 at four different doses: 10 grays, 15 grays, 20 grays, and 25
      grays. In model 2, a total of 24 pigs underwent aortic bypass with a 6-mm PTFE
      graft followed by irradiation of the distal end-to-side anastomosis at a dose of
      20 grays on day 0. In both models specimens were harvested after 6 weeks and
      studied histologically after staining with HES and orcein, histomorphometrically
      by measuring intimal hyperplasia, and immunohistochemically using actin and
      factor VIII/von Willebrand factor (F VIII/vWF). The zones of study on the
      anastomosis were separated into base of the artery to the tip and heel of the
      anastomosis and the edge of the arteriotomy. Measurements were compared using the
      Mann Whitney test. In the first-stage model designed to study IH in rabbits, mean
      intimal and medial thickness values and the intima-to-media ratio showed no
      difference between the control group and the groups irradiated at doses of 10
      grays and 15 grays (p = 0.111, p = 0.405, and p = 0.14); (p = 0.301, p = 0.206,
      and p = 0.199). Conversely, there was a significant difference between the
      control group and the groups irradiated at 20 grays and 25 grays (p < 0.0001, p =
      0.107 and p = 0.008; p = 0.008, p = 0.155, and p = 0.008). Histological
      examination demonstrated extensive changes in the wall with high-grade fibrosis
      after application of ionizing radiation. In the second-stage swine model,
      irradiation significantly inhibited development of IH at the level of anastomosis
      both at the base of the artery (p < 0.01) (tip 0.06 vs. 0.27 mm and heel 0.04 vs.
      0.36) and at the level of the arteriotomy at the suture site (p < 0.001) (0.13
      vs. 0.86 mm). Immunochemical analysis of the thickened zones showed a positive
      reaction of endothelial cells to smooth muscle actin and F VII/vWF. Like
      irradiation applied using an endoluminal source, superficial gamma ionizing
      radiation from an external source inhibits IH. Analysis of the dose effect showed
      that the overall dose must be between 15 and 20 grays. External radiation also
      reduces overall IH at the anastomosis between a prosthesis and artery. Although
      these experimental data are promising, further study will probably be necessary
      before attempting to undertake clinical trials using external beam radiation
      therapy for patients undergoing peripheral anastomoses.

PMID- 14727166
TI  - Characterization of the heme-histidine cross-link in cyanobacterial hemoglobins
      from Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7002.
AB  - The recombinant product of the hemoglobin gene of the cyanobacterium
      Synechocystis sp. PCC 6803 forms spontaneously a covalent bond linking one of the
      heme vinyl groups to a histidine located in the C-terminal helix (His117, or
      H16). The present report describes the (1)H, (15)N, and (13)C NMR spectroscopy
      experiments demonstrating that the recombinant hemoglobin from the cyanobacterium
      Synechococcus sp. PCC 7002, a protein sharing 59% identity with Synechocystis
      hemoglobin, undergoes the same facile heme adduct formation. The observation that
      the extraordinary linkage is not unique to Synechocystis hemoglobin suggests that
      it constitutes a noteworthy feature of hemoglobin in non-N(2)-fixing
      cyanobacteria, along with the previously documented bis-histidine coordination of
      the heme iron. A qualitative analysis of the hyperfine chemical shifts of the
      ferric proteins indicated that the cross-link had modest repercussions on axial
      histidine ligation and heme electronic structure. In Synechocystis hemoglobin,
      the unreacted His117 imidazole had a normal p K(a) whereas the protonation of the
      modified residue took place at lower pH. Optical experiments revealed that the
      cross-link stabilized the protein with respect to thermal and acid denaturation.
      Replacement of His117 with an alanine yielded a species inert to adduct
      formation, but inspection of the heme chemical shifts and ligand binding
      properties of the variant identified position 117 as important in seating the
      cofactor in its site and modifying the dynamic properties of the protein. A role
      for bis-histidine coordination and covalent adduct formation in heme retention is
      proposed.

PMID- 14727168
TI  - Defoliation effects on the community structure of arbuscular mycorrhizal fungi
      based on 18S rDNA sequences.
AB  - The effects of defoliation on arbuscular mycorrhizal (AM) associations in the
      field were investigated in terms of the community structure of AM fungi
      colonizing roots of grassland plants; the carbohydrate balance of the host plants
      was also determined. We focused on two plant species dominating Japanese native
      grasslands: the grazing-intolerant species Miscanthus sinensis and the grazing
      tolerant species Zoysia japonica. Community structures of AM fungi were
      determined from 18S rRNA gene sequences. The dominant fungal group in both plant
      species was the Glomus clade, which was classified into several phylogenetic
      groups based on genetic distances and topology. In Miscanthus roots, the Glomus
      Ab, Glomus-Ac, and Glomus-Ad groups were detected almost equally. In Zoysia
      roots, the Glomus-Ab group was dominant. Defoliation effects on the community
      structure of AM fungi differed between the plant species. In Miscanthus roots,
      the percentage of root length colonized (%RLC) by the Glomus-Ac and Glomus-Ad
      groups was significantly reduced by defoliation treatment. On the other hand, AM
      fungal group composition in Zoysia roots was unaffected by defoliation except on
      the last sampling date. Decreased %RLC by Glomus-Ac and Glomus-Ad coincided with
      decreased non-structural carbohydrate (NSC) levels in host plants; also,
      significant positive correlations were found between the %RLC and some NSC
      levels. On the other hand, the %RLC by Glomus-Ab in both plant species was
      unaffected by the NSC level. These results suggest that AM fungal groups have
      different carbohydrate requirements from host plants.

PMID- 14727167
TI  - On the role of the axial ligand in heme proteins: a theoretical study.
AB  - We present a systematic investigation of how the axial ligand in heme proteins
      influences the geometry, electronic structure, and spin states of the active
      site, and the energies of the reaction cycles. Using the density functional B3LYP
      method and medium-sized basis sets, we have compared models with His, His+Asp,
      Cys, Tyr, and Tyr+Arg as found in myoglobin and hemoglobin, peroxidases,
      cytochrome P450, and heme catalases, respectively. We have studied 12 reactants
      and intermediates of the reaction cycles of these enzymes, including complexes
      with H(2)O, OH(-), O(2-), CH(3)OH, O(2), H(2)O(2), and HO(2)(-) in various formal
      oxidation states of the iron ion (II to V). The results show that His gives ~0.6
      V higher reduction potentials than the other ligands. In particular, it is harder
      to reduce and protonate the O(2) complex with His than with the other ligands, in
      accordance with the O(2) carrier function of globins and the oxidative chemistry
      of the other proteins. For most properties, the trend Cys<Tyr<Tyr+Arg<His+Asp<His
      is found, reflecting the donor capacity of the various ligands. Thus, it is
      easier to reduce compound I with a His+Asp ligand than with a Cys ligand, in
      accordance with the one-electron chemistry of peroxidases and the hydroxylation
      reactions of cytochromes P450. However, the Tyr complexes have an unusually low
      affinity for all neutral ligands, giving them a slightly enhanced driving force
      in the oxidation of H(2)O(2) by compound I.

PMID- 14727169
TI  - Prophylactic treatment of known ifosfamide-induced encephalopathy for
      chemotherapy with high-dose ifosfamide?
AB  - We report about a case of advanced Ewing sarcoma in a 30-year-old woman. Initial
      treatment was started according to the Euro-Ewing 99 protocol. During the initial
      therapy, an ifosfamide-induced encephalopathy occurred as status epilepticus.
      Because of cerebral toxicity, the following chemotherapies went without
      ifosfamide. During final radiotherapy multiple lung metastasis were diagnosed.
      After two cycles of chemotherapy with cyclophosphamide and topotecan (no
      response), left thoracotomy, and palliative pneumectomy, the patient was
      transferred to our ward for further treatment. Undergoing two cycles of
      chemotherapy with ifosfamide 4 g/m(2) intravenously for 3 consecutive days
      followed by high-dose chemotherapy (HDCT) according to the ICE-regimen
      (ifosfamide 2 g/m(2), carboplatin 200 mg/m(2), and etoposide 2 x 100 mg/m(2)
      intravenously for 6 consecutive days), and peripheral blood stem cell
      transplantation (PBSCT), complete remission was achieved. Under preventive
      therapy with methylene blue, thiamin, and glucose 5% infusions, no encephalopathy
      occurred.

PMID- 14727170
TI  - Implantable venous port-related infections in cancer patients.
AB  - OBJECTIVES: To evaluate the characteristics of implantable venous port-related
      infections in patients with malignancies. PATIENTS AND METHODS: This was a 6-year
      study in which all the records of cancer patients who were diagnosed with port
      related infections were retrospectively analyzed. RESULTS: The analysis included
      36 episodes of port-related infections. The median period from port implantation
      to the episode of port-related infection was 164 days (21 to 1650 days). Of the
      36 episodes, 15 (42%) were polymicrobial infections, and 21 (58%) were gram
      negative pathogens. If only the port-related bacteremia was taken into
      consideration, gram-negative bacilli and gram-positive cocci accounted for 39 and
      7 pathogens of the total 53 isolated microorganisms (74% and 13%, respectively).
      Stenotrophomonas maltophilia and Acinetobacter baumanii were the predominant
      causal microorganisms. All except two infectious catheters were removed. No
      infection-related mortality developed. CONCLUSIONS: Gram-negative bacilli,
      especially the glucose-non-fermenting pathogens, tend to be the major
      microorganisms that account for port-related infections, and the infections run a
      benign course, even those developed in septicemia.

PMID- 14727171
TI  - Persisting differences in truth telling throughout the world.

PMID- 14727172
TI  - Plant genetic differences influence herbivore community structure: evidence from
      a hybrid willow system.
AB  - To determine the influence of plant genetic variation on community structure of
      insect herbivores, we examined the abundances of 14 herbivore species among six
      genetic classes of willow: Salix eriocephala, S. sericea, their F(1) and F(2)
      interspecific hybrids, and backcross hybrids to each parental species. We placed
      1-year-old plants, grown from seeds generated from controlled crosses, in a
      common garden. During the growing season, we censused gall-inducing flies and
      sawflies, leaf-mining insects, and leaf-folding Lepidoptera to determine the
      community structure of herbivorous insects on the six genetic classes. Our
      results provided convincing evidence that the community structure of insect
      herbivores in this hybrid willow system was shaped by genetic differences among
      the parental species and the hybrid genetic classes. Using MANOVA, we detected
      significant differences among genetic classes for both absolute and relative
      abundance of herbivores. Using canonical discriminant analysis, we found that
      centroid locations describing community structure of the insect herbivores
      differed for each genetic class. Moreover, the centroids for the four hybrid
      classes were located well outside of the range between the centroids for the
      parental species, suggesting that more than additive genetic effects of the two
      parental species influenced community formation on hybrid classes. Line-cross
      analysis suggested that plant genetic factors responsible for structuring the
      herbivore community involved epistatic effects, as well as additive and dominance
      effects. We discuss the ramifications of these results in regard to the structure
      of insect herbivore communities on plants and the implications of our findings
      for the evolution of interspecific interactions.

PMID- 14727173
TI  - Production, standing biomass and natural abundance of 15N and 13C in
      ectomycorrhizal mycelia collected at different soil depths in two forest types.
AB  - Nutrient uptake by forest trees is dependent on ectomycorrhizal (EM) mycelia that
      grow out into the soil from the mycorrhizal root tips. We estimated the
      production of EM mycelia in root free samples of pure spruce and mixed spruce-oak
      stands in southern Sweden as mycelia grown into sand-filled mesh bags placed at
      three different soil depths (0-10, 10-20 and 20-30 cm). The mesh bags were
      collected after 12 months and we found that 590+/-70 kg ha(-1) year(-1) of pure
      mycelia was produced in spruce stands and 420+/-160 kg ha(-1) year(-1) in mixed
      stands. The production of EM mycelia in the mesh bags decreased with soil depth
      in both stand types but tended to be more concentrated in the top soil in the
      mixed stands compared to the spruce stands. The fungal biomass was also
      determined in soil samples taken from different depths by using phospholipid
      fatty acids as markers for fungal biomass. Subsamples were incubated at 20
      degrees C for 5 months and the amount of fungal biomass that degraded during the
      incubation period was used as an estimate of EM fungal biomass. The EM biomass in
      the soil profile decreased with soil depth and did not differ significantly
      between the two stand types. The total EM biomass in the pure spruce stands was
      estimated to be 4.8+/-0.9 x 10(3) kg ha(-1) and in the mixed stands 5.8+/-1.1 x
      10(3) kg ha(-1) down to 70 cm depth. The biomass and production estimates of EM
      mycelia suggest a very long turnover time or that necromass has been included in
      the biomass estimates. The amount of N present in EM mycelia was estimated to be
      121 kg N ha(-1) in spruce stands and 187 kg N ha(-1) in mixed stands. The
      delta13C value for mycelia in mesh bags was not influenced by soil depth,
      indicating that the fungi obtained all their carbon from the tree roots. The
      delta13C values in mycelia collected from mixed stands were intermediate to
      values from pure spruce and pure oak stands suggesting that the EM mycelia
      received carbon from both spruce and oak trees in the mixed stands. The delta15N
      value for the EM mycelia and the surrounding soil increased with soil depth
      suggesting that they obtained their entire N from the surrounding soil.

PMID- 14727174
TI  - Is prey predation risk influenced more by increasing predator density or predator
      species richness in stream enclosures?
AB  - The direct lethal impacts and the indirect effects predators have on prey
      characteristics, such as behavior, have fitness consequences for the prey.
      Whether the level of predation risk that prey face in the presence of multiple
      predator species can be predicted from a null model that sums the risk from each
      predator species in isolation is unclear. In field enclosures, we tested whether
      the predation risk experienced by Stenonema mayfly larvae from a dragonfly larva
      ( Boyeria vinosa) and a hellgrammite ( Corydalus cornutus) together matched the
      predictions of the multiplicative risk model. We then compared whether any
      deviations from the model's predictions were larger in the presence of two
      predator species than in the presence of an equivalent density of individuals
      from either predator species alone, to determine if unique effects arise for the
      prey in the presence of multiple predator species. We also determined if prey
      moved preferentially into predator-free refuge spaces or decreased their movement
      in the presence of predators. Stenonema's risk of predation was reduced compared
      to the model's prediction, but no unique multiple predator species effects were
      present because this risk reduction was comparable in magnitude to the level
      exhibited in the presence of each predator species alone. The prey did not move
      into predator-free refuge spaces in the presence of predators in the field
      enclosures. Thus, these predators appear to interfere interspecifically and
      intraspecifically, which may facilitate the coexistence of the predators and the
      prey.

PMID- 14727175
TI  - Cytoskeletal filaments and associated proteins during restricted trophoblast
      invasion in bovine placentomes: light and transmission electron microscopy and RT
      PCR.
AB  - Trophoblast cell migration is unusual in epitheliochorial placentae but occurs in
      placentomes of cows as "restricted" trophoblast invasion of binucleated
      trophoblast giant cells (TGC). Migration may be induced by integrin binding to
      the extracellular matrix initiating two pathways: (1) conformational changes of
      the actin cytoskeleton induced by an accumulation of its associated proteins and
      (2) integrin-dependent phosphorylation of various protein kinases. In cow
      placentomes, actin, its associated proteins (alpha-actinin, vinculin) and a key
      protein kinase of the signal transduction cascade (phosphorylated mitogen
      activated protein kinase, pMAPK) were localized by immunogold-silver enhancement
      and immunoperoxidase staining at the light- and transmission electron
      microscopical levels. Findings were confirmed by amplification of specific mRNA
      transcripts by reverse transcriptase/polymerase chain reaction. Actin and alpha
      actinin were co-localized apically in mononuclear trophoblast cells, along the
      cytoplasmic membrane of TGC and apically in maternal crypt cells. The actin and
      alpha-actinin immunoreaction occurred as a band of electron-dense particles
      beneath the cytoplasmic membrane. Vinculin labelling was membrane-associated in
      TGC and in fetal and maternal endothelial cells. MAPK was observed as nuclear
      clusters in both kinds of trophoblast cells and was less dense in single uterine
      epithelial cells. Most MAPK immunoreactivity was detected in the nuclei of the
      trophoblast epithelium but was also sometimes membrane-associated in the
      cytoplasm. Thus, actin, alpha-actinin, MAPK and vinculin may be involved in the
      regulation of TGC migration. "Restricted" trophoblast invasion could serve as a
      model for invasive processes.

PMID- 14727176
TI  - Time course of angiogenesis in solid pineal autografts.
AB  - Angiogenesis and reperfusion of blood vessels were analysed qualitatively, at the
      light- and electron-microscopical levels, in solid pineal autografts placed
      intracerebrally in adult rats (post-transplantation survival times: 1, 3, 7, 10,
      14 and 28 days). Reperfusion of blood vessels was studied in sections from
      immersion-fixed brains incubated to demonstrate the endogenous peroxidase
      activity of erythrocytes within the lumen of blood vessels. The possible presence
      of the blood-brain barrier (BBB) within the grafts was also investigated by
      injecting native horseradish peroxidase (HRP) intravenously into the rats.
      Angiogenesis, the morphological and functional properties of blood vessels
      vascularizing the grafts and the survival of pineal tissue were analysed
      ultrastructurally following transplantation. Revascularization of pineal
      autografts placed into the adult host central nervous system occurred very
      slowly, requiring 7-10 days to establish anastomoses between graft and host blood
      vessels. During this process, signs of angiogenesis in pineal and cerebral
      capillaries were evident, suggesting that both contributed to graft
      revascularization. Morphological and functional studies with HRP revealed that,
      following transplantation, blood vessels at the graft-host interface or within
      pineal autografts maintained their morphological and functional properties: they
      were fenestrated and did not present a BBB to blood-borne peroxidase. Thus, after
      grafting, the presence or absence of the BBB is graft-determined. Revascularized
      pineal tissue showed good survival and pinealocytes revealed structural features
      of active secretory cells.

PMID- 14727177
TI  - Localization and expression of the glutamate transporter, excitatory amino acid
      transporter 4, within astrocytes of the rat retina.
AB  - Mechanisms for the removal of glutamate are vital for maintaining normal function
      of the retina. Five excitatory amino acid transporters have been characterized to
      date from neuronal tissue, all of which are expressed within the retina except
      excitatory amino acid transporter 4 (EAAT4). In this study we examined the
      expression and localization of the glutamate transporter EAAT4 in the rat retina
      using RT-PCR and immunocytochemistry. RT-PCR using rat EAAT4 specific primers
      revealed a prominent 296-bp product in the retina, cortex and cerebellum. The
      identity of the EAAT4 fragment was confirmed by DNA sequencing. We examined the
      tissue expression levels of EAAT4 in cortex, retina and cerebellum using real
      time PCR. The highest expression level was found in the cerebellum. Expression in
      the cortex was approximately 3.1% that of the cerebellum and the retina was found
      to have approximately 0.8% the total cerebellar EAAT4 content. In order to
      examine the specific cell types within the retina that express EAAT4, we
      performed immunocytochemistry using a rat EAAT4 specific antiserum. Cellular
      processes within the nerve fibre layer of the retina were intensely labelled for
      EAAT4. Double labelling EAAT4 with glial fibrillary acidic protein (GFAP)
      revealed extensive colocalization indicating that EAAT4 is localized within
      astrocytes within the retina. Double labelling of EAAT4 and the glutamate
      transporter EAAT1 (GLAST) revealed extensive colocalization suggesting that
      astrocytes in the retina express at least two types of glutamate transporters.
      These results suggest that astrocytes within the retina are well placed to
      provide mechanisms for glutamate removal as well as controlling cellular
      excitability.

PMID- 14727179
TI  - A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah
      pedigree.
AB  - Familial hypercholesterolemia results from mutations in the low-density
      lipoprotein (LDL) receptor or apolipoprotein B genes. We have previously reported
      the identification of a Utah autosomal-dominant hypercholesterolemia pedigree
      (kindred 1173) that did not show linkage to either of these loci (Hunt et al.
      2000). Expansion of the pedigree and increased marker density within the region
      of interest have resulted in a multipoint LOD score of 9.6 and enabled us to
      decrease the size of the linked region to approximately 7.5 Mbp. In addition, we
      were able to identify additional families sharing the same microsatellite
      haplotype. While all haplotype carriers in kindred 1173 (K1173) are affected, the
      haplotype carriers within the newly identified families are unaffected,
      suggesting that the causal mutation in K1173 had occurred after divergence of
      these pedigrees from a common ancestor. Mutation screening of genes in the region
      identified a single nucleotide variant (G-->T) present on the K1173 haplotype
      that was not present on the same haplotype in the other kindreds. This variant
      results in a D374Y missense change in the gene PCSK9.

PMID- 14727180
TI  - Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in
      Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.
AB  - The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation
      causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases
      (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To
      investigate the genetic history of this mutation in the AJ population, a
      conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144
      D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ
      individuals (15 homozygotes and 40 heterozygotes for the TSD mutation),
      suggesting the occurrence of a common founder. When two methods were used for
      analysis of linkage disequilibrium (LD) between flanking polymorphic markers and
      the disease locus and for the study of the decay of LD over time, the estimated
      age of the insertion was found to be 40+/-12 generations (95% confidence
      interval: 30-50 generations), so that the most recent common ancestor of the
      mutation-bearing chromosomes would date to the 8th-9th century. This corresponds
      with the demographic expansion of AJs in central Europe, following the founding
      of the Ashkenaz settlement in the early Middle Ages. The results are consistent
      with the geographic distribution of the main TSD mutation, 1278insTATC being more
      common in central Europe, and with the coalescent times of mutations causing two
      other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence
      of a determinant positive selection (heterozygote advantage) over the mutation is
      provided by a comparison between the estimated age of 1278insTATC and the
      probability of the current AJ frequency of the mutant allele as a function of its
      age, calculated by use of a branching-process model. Therefore, the founder
      effect in a rapidly expanding population arising from a bottleneck provides a
      robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in
      AJ individuals.

PMID- 14727181
TI  - Genetics of parkin-linked disease.
AB  - Research into Parkinson's disease (PD), once considered the archetypical non
      genetic neurodegenerative disorder, has been revolutionized by the identification
      of a number of genes, mutations of which underlie various familial forms of the
      disease. Whereas such mutations appear to exist in a relatively small number of
      individuals from a few families, the study of the function of these genes
      promises to reveal the fundamental disease pathogenesis, not only of familial
      forms of the disease, but also of the much more common sporadic PD. The
      observation that mutations in the second identified PD locus (parkin) are common
      in juvenile- and early-onset PD and increasing evidence supporting a direct role
      for parkin in late-onset disease make this gene a particularly compelling
      candidate for intensified investigation. The determination of the frequency and
      effect of parkin mutations in various subsets of PD will be crucial for
      understanding the way in which parkin is related to neurodegenerative mechanisms,
      and whether these subsets might be effectively identified and treated. In
      addition, many aspects of parkin-linked disease, originally thought to be well
      defined, have now been obscured both by genetic studies that preclude a simple
      model of disease transmission and by clinical and pathological studies that
      demonstrate broad variability in cases with parkin mutations. Future studies that
      address the issues in question should have a far-reaching impact in downstream
      biochemical studies and our understanding of parkin's role in PD.

PMID- 14727182
TI  - Structure and expression of 12-oxophytodienoate reductase (subgroup I) genes in
      pea, and characterization of the oxidoreductase activities of their recombinant
      products.
AB  - Recently, we observed that expression of a pea gene (S64) encoding an
      oxophytodienoic acid reductase (OPR) was induced by a suppressor of pea defense
      responses, secreted by the pea pathogen Mycosphaerella pinodes. Because it is
      known that OPRs are usually encoded by families of homologous genes, we screened
      for genomic and cDNA clones encoding members of this putative OPR family in pea.
      We isolated five members of the OPR gene family from a pea genomic DNA library,
      and amplified six cDNA clones, including S64, by RT-PCR (reverse transcriptase
      PCR). Sequencing analysis revealed that S64 corresponds to PsOPR2, and the amino
      acid sequences of the predicted products of the six OPR-like genes shared more
      than 80% identity with each other. Based on their sequence similarity, all these
      OPR-like genes code for OPRs of subgroup I, i.e., enzymes which are not required
      for jasmonic acid biosynthesis. However, the genes varied in their exon/intron
      organization and in their promoter sequences. To investigate the expression of
      each individual OPR-like gene, RT-PCR was performed using gene-specific primers.
      The results indicated that the OPR-like gene most strongly induced by the
      inoculation of pea plants with a compatible pathogen and by treatment with the
      suppressor from M. pinodes was PsOPR2. Furthermore, the ability of the six
      recombinant OPR-like proteins to reduce a model substrate, 2-cyclohexen-1-one (2
      CyHE), was investigated. The results indicated that PsOPR1, 4 and 6 display
      robust activity, and PsOPR2 has a most remarkable ability to reduce 2-CyHE,
      whereas PsOPR3 has little and PsOPR5 does not reduce this compound. Thus, the six
      OPR-like proteins can be classified into four types. Interestingly, the gene
      structures, expression profiles, and enzymatic activities used to classify each
      member of the pea OPR-like gene family are clearly correlated, indicating that
      each member of this OPR-like family has a distinct function.

PMID- 14727183
TI  - Differential expression of an S-adenosyl-L-methionine decarboxylase gene involved
      in polyamine biosynthesis under low temperature stress in japonica and indica
      rice genotypes.
AB  - We have investigated the regulation of the rice (Oryza sativa) gene OsSAMDC,
      which encodes an S-adenosyl-L-methionine decarboxylase (SAMDC) involved in
      polyamine biosynthesis. Clones representing genes differentially expressed at 5
      degrees C and 20 degrees C were isolated from a cDNA library prepared from the
      chilling-tolerant japonica-type cultivar Yukihikari. The full-length OsSAMDC cDNA
      consists of 1560 bp, with the longest ORF encoding a polypeptide of 398 amino
      acids. Southern analysis indicated that there are two types of gene for SAMDC in
      the Yukihikari genome. Analysis of the expression of OsSAMDC by Northern
      hybridization revealed relatively high levels of mRNA in the leaves, nodes and
      internodes. We also analyzed the response of OsSAMDC to various abiotic stress
      treatments and plant hormones. Upon exposure to cold stress (5 degrees C) the
      level of OsSAMDC transcripts in the cold-resistant Yukihikari genotype continued
      to increase for up to 72 h. In contrast, there was no change in OsSAMDC
      transcription in the susceptible indica cultivar TKM9 under the same conditions.
      Ethephon induced the accumulation of OsSAMDC transcripts to similar extents in
      both genotypes. Examination of polyamine levels in the cold-resistant Yukihikari
      genotype revealed that spermidine levels were elevated during the course of cold
      treatment. These results suggest that the induction of the OsSAMDC gene in
      response to cold may be used as a molecular marker for the ability of rice
      seedlings to withstand exposure to low temperatures.

PMID- 14727184
TI  - The fertility restorer genes X and T alter the transcripts of a novel
      mitochondrial gene implicated in CMS1 in chives (Allium schoenoprasum L.).
AB  - A chimeric mitochondrial gene configuration, mainly derived from sequences
      associated with the essential genes atp9 and atp6, was isolated from the
      sterility-inducing cytoplasm of the CMS1 system in chives (Allium schoenoprasum
      L.). This sequence is not found in four other cytoplasm types from chives;
      however, two copies are present in the mitochondrial DNA of CMS1-inducing
      cytoplasm, whose 5'-sequences are homologous to those of the atp9 gene. We
      provide evidence to show that one of the two CMS1-specific copies is actively
      transcribed, and two transcripts which terminate at the same position but differ
      in their 5'initiation sites were localized using the RACE technique. These
      transcripts of 942 and 961 nt, respectively, were confirmed to be the major
      products of this gene in CMS1 plants by Northern hybridization. However, smaller
      transcripts were found to accumulate in plants in which fertility had been
      restored. Restoration of fertility was induced either by the gene X, or the gene
      T at high temperatures. In (S1) X. genotypes a transcript with an estimated size
      of 440 nt was detected in all tissues examined. An additional hybridization
      signal with an estimated size of approximately 850 nt is expressed in temperature
      sensitive plants [(S1) xxT.], and the intensity of a minor 350-nt transcript is
      enhanced. These latter alterations, conditioned by the gene T, occur
      independently of the growth temperature, but are limited to the flowers; they
      were not observed in leaves. The CMS1 transcripts are edited at seven positions
      and contain an ORF with a maximum coding capacity of 780 nt (containing the start
      codon derived from the atp9 gene in-frame). Use of the third in-frame start codon
      would result in the synthesis of a protein of a size very close to that of a
      previously described CMS1-specific protein, which has an apparent molecular
      weight of 18 kDa. The coding sequence that begins at this third in-frame start
      codon is also present in the sterility-inducing cytoplasms (S) and (T) in the
      onion, and absent in (N) cytoplasm.

PMID- 14727185
TI  - The use of CpG as an adjuvant to Toxoplasma gondii vaccination.
AB  - Unmethylated CpG dinucleotides have been found to stimulate general immune
      responses in mammals. CpG motifs have further been shown to be potent adjuvants
      when used in conjunction with vaccines for viral and bacterial organisms. It was
      necessary to determine whether these CpG motifs will also enhance immune
      responses in parasitic diseases. We therefore decided to test the effect of CpG
      adjuventation on immunization with a temperature-sensitive mutant (ts4) strain of
      Toxoplasma gondii. Mice were divided into groups receiving either ts4 only, CpG
      only, ts4 with CpG, or untreated controls. Mice were challenged with a lethal
      dose of T. gondii (RH strain) tachyzoites 28 days after vaccination. There were
      significant differences observed between the ts4-only group and the other three
      groups with regards to antibody isotype and survival, with the former group
      surviving lethal challenge. CpG adjuventation appeared to not enhance survival.

PMID- 14727186
TI  - Polymerase chain reaction for detection of patent infections of Echinococcus
      granulosus ("sheep strain") in naturally infected dogs.
AB  - Polymerase chain reaction (PCR) for the identification of eggs of the tapeworm
      Echinococcus granulosus ("sheep strain") was evaluated with primers derived from
      mitochondrial sequences. Specificity of these primers was confirmed by
      investigating DNA of other strains of E. granulosus and of 14 helminth species
      which inhabit the intestines of dogs. This PCR assay was used to investigate 131
      purged dogs from Kazakhstan. Eighteen dogs harboured Echinococcus worms, ten of
      them in mixed infections with Taenia spp. Coproantigen detection was positive in
      15 and taeniid eggs could be recovered from 13 of these specimens. Eight of the
      egg-containing samples were positive in the PCR for E. granulosus and four in a
      Echinococcus multilocularis -specific PCR revealing one mixed infection. Egg
      containing faeces from two dogs harbouring both Taenia spp. and Echinococcus spp.
      were negative in both PCRs. The combination of egg isolation and PCR will also be
      of value in epidemiological studies when investigating environmental samples.

PMID- 14727187
TI  - Molecular characterization of Enterocytozoon bieneusi in cattle indicates that
      only some isolates have zoonotic potential.
AB  - In this study, 338 fecal samples were analyzed for Enterocytozoon bieneusi from
      cattle farms in Florida, Maryland, Michigan, New York, North Carolina,
      Pennsylvania, Virginia, and Portugal. The internal transcribed spacer region (392
      bp) of the rRNA gene of E. bieneusi was amplified using a nested PCR protocol.
      Thirty-two E. bieneusi-PCR positive samples were sequenced. A high degree of
      genetic polymorphism, represented by five distinct genotypes (BEB1-BEB5), was
      found among the E. bieneusi isolates from cattle. Most of the isolates formed a
      distinct cluster consisting of only the four cattle genotypes, but six isolates
      of a genotype clustered together with E. bieneusi genotypes from humans and other
      domestic animals. Therefore, only some E. bieneusi isolates from cattle may be of
      public health importance.

PMID- 14727188
TI  - Molecular profiles of Trypanosoma brucei, T. evansi and T. equiperdum stocks
      revealed by the random amplified polymorphic DNA method.
AB  - A total of 20 random primers (10-mers) were used to amplify RAPD markers from the
      genomic DNA of four Trypanosoma brucei stocks from East and West Africa, four T.
      evansi stocks from Africa, Asia and South America and one T. equiperdum stock
      from Asia. Between 65 and 88 reproducible fragments ranging from 0.25 to 2.15 kb
      were generated from these stocks depending on the stock/primer combination. The
      similarity coefficient (SC) among the stocks of T. brucei from Kenya, Nigeria,
      Tanzania and Zambia ranged from 62.9% to 74.0% (average: 67.6%). The SC among the
      stocks of T. evansi from Kenya, China and Brazil was 76.4%-95.5% (average:
      86.4%), while the SC between T. evansi stock from China and Brazil was 95.5%. For
      T. evansi and T. equiperdum, the SC among the stocks ranged from 81.2% to 94.4%
      (average: 87.6%). As for the SC among the stocks of T. brucei and T. evansi, it
      was found to be from 54.7% to 80.3% (average: 68.0%) and the SC among stocks of
      T. brucei and T. equiperdum was from 59.4% to 76.9% (average: 68.1%). Our results
      indicate that the stocks of T. evansi from China and from Brazil are more closely
      related to the stock of T. equiperdum from China than to the stocks of T. evansi
      isolated from Kenya and to the stocks of T. brucei. In addition, our results
      further support the hypothesis that T. evansi stocks from China and Brazil could
      have arisen from a single lineage. The possible evolution of T. evansi and T.
      equiperdum is also discussed.

PMID- 14727189
TI  - A novel Cryptosporidium parvum antigen, CP2, preferentially associates with
      membranous structures.
AB  - The present study addresses the cloning and characterization of a Cryptosporidium
      parvum antigen, CP2. Sequencing of cDNA and genomic clones revealed a novel gene
      capable of coding a message of 2,136 nucleotides flanked by 28 and 140
      nucleotides of the 5'- and 3'-noncoding regions, respectively. The deduced amino
      acid sequence suggests that CP2 is a secreted and/or membrane protein.
      Immunofluorescence microscopy detected CP2 enrichment in sporozoites that
      subsequently appeared to encase type I meronts in infected HCT-8 cells.
      Immunogold electron microscopy revealed that CP2 consistently localized to
      membranous structures throughout development. In addition, progression from
      macrogametocyte to sporulated oocyst revealed CP2 initially at the periphery of
      amylopectin-like granules, in the cytoplasm and discrete vesicles, the
      parasitophorous vacuole, on the surface of sporozoites, and finally on the
      parasitophorous vacuole membrane (PVM). The observed expression pattern suggests
      that CP2 may be involved in the invasion process and/or PVM integrity.

PMID- 14727191
TI  - [Towards early detection of schizophrenia in outpatient care].

PMID- 14727190
TI  - NADH-ubiquinone oxidoreductase activity in the kinetoplasts of the plant
      trypanosomatid Phytomonas serpens.
AB  - NADH-ubiquinone oxidoreductase activity is present in mitochondrial lysates of
      Phytomonas serpens. Rotenone at 2-10 microM inhibited the activity 50-75%,
      indicating that it belongs to respiratory complex I. The activity was also
      inhibited 50-60% in the presence of 10-30 nM atovaquone suggesting that
      inhibition of complex I represents a likely mechanism of the known
      antileishmanial activity of this drug. The complex was partially purified by
      chromatography on DEAE-Sepharose CL-6B and gel-filtration on Sepharose CL-2B. The
      NADH:ubiquinone oxidoreductase activity in this preparation was completely
      inactivated by 20 nM atovaquone. The partially purified complex was present in a
      low amount and its subunits could not be discerned by staining with Coomassie.
      However, one of its components, a homologue of the 39 kDa subunit of the bovine
      complex I, was identified immunochemically in the original lysate and in the
      partially purified material.

PMID- 14727192
TI  - [Liaison psychiatry in the prison of Rottenburg (Germany)].
AB  - The aim of this study was to get an idea of the need of psychiatric therapy in a
      prison. We report on the period May 2000 to January 2002. 60 medical files with
      the sociodemographic variables and the psychiatric diagnosis were evaluated. 45 %
      of the examined prisoners had a diagnosis of drug- or alcohol dependency and 31.3
      % had a diagnosis of a schizophrenia. In 26.7 % the therapy was successful and
      the prisoners improved. This results show a great need of psychiatric therapy in
      a prison. Also in a prison improvements in the course of psychic disturbances are
      possible.

PMID- 14727193
TI  - [Ethnic minorities and aggressive behaviour in psychiatric in-patients: an
      investigation using a "Matched-Pair" design].
AB  - In a group of 105 mentally ill immigrants we investigated the intensity and the
      frequency of aggressive behaviour at the time of admission with the help of two
      standardized instruments: the "Social Dysfunction and Aggression Scale" (SDAS)
      and the "Modified Overt Aggression Scale" (MOAS). As many as possible collateral
      informants were contacted to gather all information available for the
      aggressiveness rating. The immigrant group was compared to a matched group of
      German patients. 416 German patients had to be investigated until 105 of them
      fulfilled the matching criteria. The matching variables were: age, gender,
      diagnosis (ICD-10), severity of mental illness (CGI) and social status. The
      physicians who carried out the matching process and who carried out the
      aggression-rating were "blind" to the aim of the investigation. We found out that
      there was no significant difference between immigrants and German patients when
      the sum-scores of the SDAS and the MOAS are compared (N = 210). When SDAS single
      variables were compared German patients had a higher severity and frequency of
      "physical violence towards other persons". We interpreted this finding as an
      increased level of disinhibition which may be correlated to a higher acceptance
      of aggressive behaviour in German culture compared to normative beliefs of
      Mediterranean immigrants.

PMID- 14727194
TI  - [A Qualitative Follow-Up Assessment two Years after Inpatient Crisis
      Intervention].
AB  - OBJECTIVE: 34 patients (50 % adjustment disorder) were investigated at admission,
      at discharge and 2 years after participating in a 2-week crisis intervention
      program. METHOD: Measures included SCL-90R, BDI and the Giessen-Test at all time
      points and a semi-structured interview at follow-up. RESULTS: Patients still
      suffered from residual symptoms at follow-up. Patients with a partner conflict
      were readmitted to inpatient care more often. Focussing the patient's perceived
      predominant problem during crisis intervention had a favourite follow-up outcome.
      CONCLUSIONS: Therapists should ensure repetitively that the predominant
      psychosocial problem according to the patient's view stays the focus of a crisis
      intervention. Individual assessment, especially regarding the preferred treatment
      modality during crisis intervention, may help to plan post intervention
      treatment.

PMID- 14727195
TI  - [Comparative studies on in-patients following suicide attempts].
AB  - In the course of the survey a total of 311 patients were examined, who had been
      admitted for treatment to the clinic for Psychiatry, Psychotherapy and Neurology
      of the Vogtland-Klinikum Plauen GmbH, following suicide attempts in the years
      1960, 1970, 1980, 1990 and 1995. Simultaneously, a survey of successful suicide
      attempts in the city of Plauen was carried out. The main point of interest was
      the motivation for the suicide attempts and the personal situation of the persons
      involved, most especially the influence of the social changes after 1990, towards
      their suicidal behaviour. As expected, the number of patients in full-time
      employment in 1995 was noticeably lower than in the preceding years, despite the
      fact that unemployment was not more often given as a reason for suicide attempts.
      In all the periods examined, conflicts within partnership structures played an
      outstanding role amongst the reasons for attempted suicides. An increase in
      attempted suicides due to endogenous depression was observed only in 1990.

PMID- 14727196
TI  - [Voluntariness and coercion in patients with schizophrenia].
AB  - OBJECTIVE: Associations between voluntariness of treatment, success of treatment,
      and number of hospital admissions should be examined. PATIENTS: 88 consecutive
      admissions with ICD-10 F2 disorders were assessed using the PANSS and the GAF at
      admission and discharge. Voluntariness was assessed regarding admission, hospital
      stay, medication, time of discharge, and treatment continuation in four degrees
      for each category. RESULTS: Voluntariness increased significantly with the number
      of hospital admissions in women. Outcome measures (PANSS and GAF differences
      admission/discharge and the respective differences divided by number of inpatient
      days) were not significantly related to any aspect of voluntariness.
      Voluntariness was negatively associated with PANSS-scores at admission, but not
      at discharge. Aggressive behaviour and coercive measures were observed more
      frequently in patients with aspects of involuntariness. CONCLUSION: The short
      term success of treatment in acute schizophrenic episodes seems not to be
      affected by measures of compulsive treatment. There is some evidence that
      experiences with former inpatient treatment increase the degree of voluntariness
      in women.

PMID- 14727197
TI  - [Compulsory admission of mentally ill patients in European union member States].
AB  - AIMS: A standardised and systematic analysis of commitment laws in the EU-Member
      States is still missing. This study aimed at gathering, describing and analysing
      information on the differences or similarities of legal frameworks for
      involuntary placement and treatment of mentally ill patients across the European
      Union Member States. METHOD: Information was gathered by means of a detailed
      questionnaire filled in by experts from all EU Member States. Legal criteria for
      compulsory admission, details of the assessment and decision process of
      compulsory admission and epidemiological data are outlined. RESULTS: Although
      common patterns among Member States can be identified upon comparison of crucial
      legislative or procedural details, these patterns are far from being consistent
      across all analysed items or approaches. With regard to compulsory admission
      quotas no significant influence of legal commitment criteria and the involvement
      of judicial authorities could be found but Member States with an obligatory
      inclusion of a legal representative during the commitment procedure showed
      significantly lower compulsory admission quotas. CONCLUSION: Results of this
      study show the strong necessity for further research in this field. Common
      international health reporting standards as annually updated involuntary
      placement rates detailed for regular and emergency cases seem to be essential.

PMID- 14727198
TI  - [Notes concerning the uncritical handling of the diagnosis "Kleptomania"].
AB  - The diagnosis kleptomania is based on diagnostic criteria which describe a
      particular distinctive behaviour. Both the DSM-IV and the WHO-ICD10 neglect the
      different etiologic possibilities. The high co-morbidity of kleptomania with
      other mental disorders is another problem. The assessment of legal responsibility
      should not only focus on the analysis of the stealing act, but has to consider
      potential associated psychopathology. It appears insufficient to describe complex
      organic disorders (for example a dementia) with the term kleptomania. However,
      the forensic relevance of kleptomania, which seems to be very rare, is a result
      of symptom progression, decreasing satisfaction and feelings of shame or
      distress.

PMID- 14727199
TI  - Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991
      2000.
AB  - Candida species are among the most common bloodstream pathogens in the United
      States, where the emergence of azole-resistant Candida glabrata and Candida
      krusei are major concerns. Recent comprehensive longitudinal data from Europe are
      lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17
      university and university-affiliated hospitals representing 79% of all tertiary
      care hospital beds in Switzerland. The number of transplantations and bloodstream
      infections increased significantly (P<.001). A total of 1137 episodes of
      candidemia were observed: Candida species ranked seventh among etiologic agents
      (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a
      10-year period. C. albicans remained the predominant Candida species recovered
      (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the
      incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei
      remained rare (2%). Fluconazole consumption increased significantly (P<.001).
      Despite increasing high-risk activities, the incidence of candidemia remained
      unchanged, and no shift to resistant species occurred.

PMID- 14727200
TI  - Intrathecal baclofen for the treatment of tetanus.
AB  - Tetanus remains a serious problem in public health, particularly in developing
      countries, despite efficient prevention programs. A retrospective study was
      conducted at an infectious diseases intensive care unit during 1998-2003
      involving patients admitted with grade III tetanus. The aim of the study was to
      evaluate the efficacy and safety of intrathecal baclofen for the treatment of
      tetanus. Lumbar puncture was performed, and a subarachnoid catheter was inserted
      for drug administration. An intrathecal bolus of baclofen was followed by a
      continuous infusion of 20 microg/h, until a maximum daily dose of 2 mg was
      provided. Twenty-two patients were treated overall. Control of the symptoms was
      achieved in all patients but one. Seven patients had colonization of the
      catheter, and 1 patient developed meningitis. All patients except one recovered.
      In our study, this means of treatment was efficacious and well tolerated.

PMID- 14727201
TI  - Multidrug-resistant Escherichia coli clonal groups causing community-acquired
      pyelonephritis.
AB  - From October 1999 through January 2000, an Escherichia coli clonal group
      (designated "CgA") was isolated from the urine of nearly one-half of all women
      with urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole (TMP
      SMZ)-resistant E. coli in a California community. This study describes the
      prevalence of pyelonephritis caused by CgA in the same community. E. coli
      isolates were characterized by enterobacterial repetitive intergenic consensus
      (ERIC2) polymerase chain reaction (PCR), serogrouping, and pulsed-field gel
      electrophoresis. Fourteen (11%) of 130 women with UTIs received a diagnosis of
      pyelonephritis. CgA was associated with 4 (57%) of the 7 pyelonephritis cases
      caused by TMP-SMZ-resistant E. coli and was associated with none of the cases
      caused by TMP-SMZ-susceptible E. coli (P<.02). Six (86%) of these TMP-SMZ
      resistant E. coli isolates belonged to 2 distinct ERIC2 PCR-defined clonal
      groups, whereas all of the TMP-SMZ-susceptible E. coli strains had unique
      fingerprints (P<.001). The prevalence of antimicrobial-resistant pyelonephritis
      in a community may be affected by a limited number of E. coli clonal groups.

PMID- 14727202
TI  - Blastoschizomyces capitatus infection in patients with leukemia: report of 26
      cases.
AB  - Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25
      patients at 7 tertiary care hematology units in Spain over a 10-year period. Most
      patients (92%) had acute leukemia and developed infection during a period of
      severe and prolonged neutropenia. Two patients had esophagitis, and the rest had
      invasive infection. Fungemia (20 cases) was a common finding, with frequent
      visceral dissemination. The 30-day mortality associated with this infection was
      52%, compared with 57% among patients with systemic infection. In a univariate
      analysis, the following 3 variables had a positive impact on 30-day survival:
      removal of the central venous catheter within 5 days after the onset of infection
      (P=.02), a good performance status (P=.003), and receipt of systemic prophylactic
      or empirical antifungal therapy before infection onset (P=.006). Outcome for
      neutropenic patients with B. capitatus infection is still poor. Rapid removal of
      the central venous catheter and novel antifungal therapies are recommended for
      treatment of this rare infection.

PMID- 14727203
TI  - Depressed natural killer cell cytotoxicity against Plasmodium falciparum-infected
      erythrocytes during first pregnancies.
AB  - We measured natural killer (NK) cell cytotoxicity and cortisol and prolactin
      concentrations in peripheral venous blood samples obtained from pregnant Gabonese
      women at the time of delivery. The NK cell-mediated cytotoxicity against
      Plasmodium falciparum-infected erythrocytes in vitro was lower in samples
      obtained from primiparous women than in samples obtained from multiparous women;
      cortisol concentrations were significantly higher in primiparous women than in
      multiparous women, and prolactin concentrations were significantly lower. The
      highest cortisol concentrations were found in the plasma of P. falciparum
      infected primiparous women. A positive correlation was found between cortisol
      concentration and parasite load; an inverse correlation was found between the
      magnitude of the NK cell cytolytic effect and cortisol production. A positive
      correlation was found between this effect and prolactin production. Thus,
      depressed NK cell cytotoxicity against P. falciparum-infected erythrocytes is
      correlated with high cortisol concentrations and may contribute to increased
      susceptibility to malaria during pregnancy.

PMID- 14727204
TI  - Long-term antibiotic cost savings from a comprehensive intervention program in a
      medical department of a university-affiliated teaching hospital.
AB  - We tested a low-cost, multifaceted intervention program comprising formulary
      restriction measures, continued comprehensive education, and guidelines to
      improve in-hospital use of antibiotics and related costs. In a short-term
      analysis, total antibiotic consumption per patient admitted, which was expressed
      as defined daily doses (DDD), decreased by 36% (P < .001), and intravenous DDDs
      decreased by 46% (P < .01). Overall expenditures for antibiotic treatment
      decreased by 53% (100 US dollars per patient admitted). The 2 main cost-lowering
      factors were a reduction in prescription of antibiotics (35% fewer treatments; P
      < .0001) and more diligent use of 5 broad-spectrum antibiotics (23% vs. 10% of
      treatments; P = .001). Quality of care was not compromised. A pharmacy-based,
      prospective, long-term surveillance of DDDs and costs over 4 years showed an
      ongoing effect. This comprehensive intervention program, which aimed to reduce
      antibiotic consumption and costs, was highly successful and had long-lasting
      effects.

PMID- 14727205
TI  - Predicting bacteremia at the bedside.
AB  - Our aim was to develop a clinical prediction rule for detection of bacteremia in
      a cohort of patients observed prospectively at a reference center in Medellin,
      Colombia. The significant predictors of bacteremia were an age of >or=30 years
      (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.19-3.60), a heart rate of
      >or=90 beats/min (OR, 1.90; 95% CI, 1.13-3.17), a temperature of >or=37.8 degrees
      C (OR, 2.42; 95% CI, 1.41-4.14), a leukocyte count of >or=12,000 cells/microL
      (OR, 2.40; 95% CI, 1.41-4.10), use of a central venous catheter (OR, 1.89; 95%
      CI, 1.02-3.50), and a length of hospitalization of >or=10 days (OR, 2.02; 95% CI,
      1.25-3.24). The Hosmer-Lemeshow test revealed a goodness-of-fit of 2.99 (P=.981),
      and the area under the receiver operating characteristics curve was 0.7186.
      Simple variables obtained from the clinical history of patients are associated
      with bloodstream infection in a reproducible fashion and should be instrumental
      for prioritizing the requests for blood cultures by clinicians.

PMID- 14727206
TI  - Short-course rifampin and pyrazinamide compared with isoniazid for latent
      tuberculosis infection: a cost-effectiveness analysis based on a multicenter
      clinical trial.
AB  - Two months of treatment with rifampin-pyrazinamide (RZ) and 9 months of treatment
      with isoniazid are both recommended for treatment of latent tuberculosis
      infection in adults without human immunodeficiency virus infection, but the
      relative cost-effectiveness of these 2 treatments is unknown. We used a Markov
      model to conduct a cost-effectiveness analysis to assess the impact on life
      expectancy and costs based on the results of a recent clinical trial that
      compared the rates of adverse events and completion of the 2 treatment regimens.
      Compared with no treatment, both regimens increased life expectancy by 1.2 years,
      but RZ cost 273 dollars more per patient. Sensitivity analyses showed that,
      assuming equal efficacy between the 2 regimens, there was no threshold completion
      rate for RZ at which the 2 treatments would be of equal net cost. Under most
      circumstances, treatment of latent tuberculosis infection with isoniazid is cost
      saving than treatment with RZ.

PMID- 14727207
TI  - Epidemiology of hepatitis B infection among expatriates in Nigeria.
AB  - Adult expatriates in countries where hepatitis B virus (HBV) is highly endemic
      have an increased risk of HBV infection, but little is known about risks to their
      children or about patterns of spread. The epidemiology of HBV infection was
      studied among 124 unvaccinated Dutch missionaries and family members who lived in
      a rural area of Nigeria. Antibodies to hepatitis B core antigen were found in 5
      (9.8%) of 51 adults (incidence rate, 1.7 per 1000 person-months at risk [PMAR])
      and 9 (12.3%) of 73 children (incidence rate, 2.8 per 1000 PMAR). Vertical
      transmission of HBV was a likely source of infection in 1 child and was a
      possible source of infection in 2 others. The prevalence of HBV infection showed
      strong family clustering (P<.0001), was associated with a history of temporary
      adoption of Nigerian children (P=.004), and increased with both the number of
      adoptive children (P=.009) and the total time that these children had stayed in
      the family (P=.036). Horizontal transmission from adoptive Nigerian children
      probably played an important role in the spread of HBV infection in this
      expatriate community.

PMID- 14727208
TI  - Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus
      lipid formulations.
AB  - In Bihar, India, where visceral leishmaniasis is hyperendemic, amphotericin B
      deoxycholate is now first-line parenteral treatment. To test the efficacy of
      amphotericin B deoxycholate versus that of its lipid formulations, Indian
      patients were randomized to receive treatment with amphotericin B deoxycholate (1
      mg/kg on alternate days for 30 days; n=51), liposomal amphotericin B (2 mg/kg per
      day for 5 days; n=51), or amphotericin B lipid complex (2 mg/kg per day for 5
      days; n=51). Infusion-associated reactions were frequent and persistent in
      subjects treated with amphotericin B deoxycholate. The illness of 3 patients
      failed to respond to treatment, and 5 patients experienced relapse. Final cure
      rates were similar. Estimated total treatment costs for a 25-kg patient-417
      dollars for amphotericin B deoxycholate, 872 dollars for liposomal amphotericin
      B, and 947 dollars for amphotericin B lipid complex-differed as a result of drug
      cost. Substantial reductions (approximately 60%) in the price of liposomal
      amphotericin B and amphotericin B lipid complex would make treatment costs
      comparable to that of amphotericin B deoxycholate, permitting administration of
      short-course regimens in India.

PMID- 14727209
TI  - Reducing intracranial pressure may increase survival among patients with
      bacterial meningitis.
AB  - We reported findings concerning continuous intracranial pressure (ICP) and
      cerebral perfusion pressure (CPP) measurements and mortality in patients with
      severe bacterial meningitis treated on the basis of an ICP-targeted approach.
      Eighteen patients with severe bacterial meningitis were admitted for
      neurointensive care at Umea University Hospital (Umea, Sweden). In 15 patients,
      ICP was measured continuously through an ICP measuring device. During care, all
      patients but one developed intracranial hypertension with an ICP of >or=15 mm Hg
      (14 [93%] of 15 patients). Ten (67%) of 15 patients survived and were discharged,
      and 5 patients (33%) died. Mean ICP was significantly higher and CPP was markedly
      decreased in nonsurvivors, compared with survivors. Among the survivors, ICP was
      gradually reduced. Treatment of patients with severe bacterial meningitis should
      include neurointensive care and continuous ICP measurement. Increased ICP may be
      reduced by using the ICP-targeted therapy that closely resembles the "Lund
      concept."

PMID- 14727210
TI  - Evaluation of a rapid quantitative diagnostic test for adenovirus type 4.
AB  - Acute respiratory disease (ARD) due to adenoviruses is a reemerging disease in
      military recruits. It is a challenge for clinicians to accurately diagnose this
      disease and to appropriately treat affected individuals. This study investigated
      the utility of a quantitative, rapid-cycle, real-time fluorogenic polymerase
      chain reaction (PCR) technique for detecting adenovirus type 4 (Ad4) in a
      clinical setting. Throat swab specimens and clinical data were collected from US
      Army basic trainees hospitalized with ARD at Fort Jackson, South Carolina. A
      total of 140 throat swab specimens were collected from 83 subjects. Rapid PCR
      results (obtained in <2 h) had a sensitivity of 100% and a specificity of 100%,
      compared with viral culture. There was no difference, qualitative or
      quantitative, between frozen and fresh samples for PCR detection of Ad4.
      Individuals with test results positive for Ad4 were hospitalized longer than were
      individuals with negative test results. Higher virus loads at hospital admission
      corresponded to longer lengths of stay for Ad4-positive subjects.

PMID- 14727211
TI  - Optimizing the care of minority patients with HIV/AIDS.
AB  - Persons belonging to racial/ethnic minorities are disproportionately affected by
      human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency
      syndrome (AIDS) in the United States, with higher numbers of infected individuals
      and higher HIV/AIDS-related death rates. Despite its substantial medical toll
      among minorities, HIV/AIDS has had a complex sociocultural legacy in many
      minority communities in the United States, especially in the African American
      community, which can present a challenge for patients and medical care providers.
      Many studies have found that minorities receiving care for HIV/AIDS are less
      likely to be satisfied with their HIV care and less likely to receive highly
      active antiretroviral therapy (HAART) than are other patients. The root causes of
      these disparities in care have not yet been well delineated. However, clinicians
      can optimize the care they provide for minority patients by using a cultural
      competence framework, enhancing patient-provider communication, diversifying
      their clinical staff, proactively enhancing receipt of HAART, and being attentive
      to issues related to adherence to HAART.

PMID- 14727212
TI  - GB virus type C coinfection in HIV-infected African mothers and their infants,
      KwaZulu Natal, South Africa.
AB  - GB virus type C (GBV-C) infection was studied in a convenience sample of 75
      antiretroviral (ART)-naive African mothers with human immunodeficiency virus
      infection and their infants. GBV-C RNA was extracted from serum and amplified by
      reverse-transcriptase polymerase chain reaction. Twenty-seven (36%) of these 75
      HIV-infected women tested positive for GBV-C RNA. To study transmission dynamics,
      we chose a random subsample of 20 of these women and their infants. In this
      cohort, there was evidence of postnatal transmission of GBV-C; however, it was
      not possible to demonstrate evidence of in utero or intrapartum transmission. In
      this pilot observational study, transmission of HIV from mother-to-infant occurs
      independently of the GBV-C infection status of the mother. The immunological
      indices measured tend to suggest an association with protection and or delayed
      progression of HIV disease in GBV-C-infected mothers.

PMID- 14727213
TI  - GB virus type C: a virus in search of a disease or a role in HIV therapy?

PMID- 14727214
TI  - CD38 expression in CD8+ T cells predicts virological failure in HIV type 1
      infected children receiving antiretroviral therapy.
AB  - An observational study of children vertically infected with human
      immunodeficiency virus type 1 (HIV-1) was performed to determine the role of CD38
      expression in CD8(+) T cells as prognostic marker of virological failure in
      children receiving HAART. We studied 42 children who were receiving
      antiretroviral therapy and who had an undetectable virus load (uVL), and we found
      a negative correlation between CD38 expression in CD8(+) T cells and the duration
      of uVL. We selected 17 HIV-1-infected children with CD38 values close to the
      baseline level (i.e., the first uVL achieved), and we distributed the children
      into 2 groups on the basis of median CD38 value in CD8(+) T cells. Children with
      CD38 values in CD8(+) T cells that were higher than the median had a higher
      incidence and relative risk of virological failure than did those with values
      lower than the median. In conclusion, we demonstrate for the first time that
      CD8(+)CD38(+) T cell count is a good prognostic marker of therapeutic failure in
      HIV-1-infected children.

PMID- 14727215
TI  - Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral
      therapy.
AB  - To analyze the impact of highly active antiretroviral therapy (HAART) on the
      characteristics and outcome of sarcoidosis in patients infected with human
      immunodeficiency virus (HIV), we identified HIV-infected patients in whom
      sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of
      the pneumology departments of 12 hospitals in the Paris region (France).
      Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving
      HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of
      sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the
      mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several
      months after HAART introduction, when the CD4 cell count had increased and the
      plasma HIV load had decreased. Clinical and radiological characteristics,
      laboratory values for bronchoalveolar lavage fluid samples, and outcome after a
      long follow-up were similar for the patients receiving HAART and for HIV
      uninfected patients.

PMID- 14727216
TI  - Pharmacokinetic interaction between rifampin and the combination of indinavir and
      low-dose ritonavir in HIV-infected patients.
AB  - Rifampin is an important drug in the treatment of tuberculosis, but
      administration of rifampin in combination with protease inhibitors is complicated
      because of drug-drug interactions. A prospective, controlled, multiple-dose study
      involving 6 HIV-infected patients receiving a combination of indinavir (800 mg)
      and ritonavir (100 mg) twice a day was performed to evaluate whether the inducing
      effect of rifampin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4
      could be overcome by the inhibitory effect of ritonavir. Pharmacokinetic
      evaluations of steady-state concentrations of indinavir and ritonavir were
      performed before and after administration of rifampin (300 mg every day for 4
      days). An 87% reduction (from 837 to 112 ng/mL) in median indinavir and a 94%
      reduction (from 431 to 27 ng/mL) in median ritonavir concentrations were seen 12
      h after the last dose of rifampin was administered (P=.031). These results
      strongly indicate that the administration of rifampin with a combination of
      indinavir (800 mg) and ritonavir (100 mg) could lead to subtherapeutic
      concentrations of indinavir.

PMID- 14727217
TI  - Analyzing sleep abnormalities in HIV-infected patients treated with Efavirenz.
AB  - Ambulatory electroencephalogram monitoring was performed for 18 HIV-infected
      subjects treated with efavirenz with and without insomnia and for 13 healthy
      control subjects. All patients receiving efavirenz had longer sleep latencies and
      shorter duration of deep sleep, although poor sleepers also showed reduced sleep
      efficiency and shorter duration of rapid eye movement sleep. Efavirenz plasma
      levels were higher in patients with insomnia and/or reduced sleep efficiency.

PMID- 14727218
TI  - Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response
      to salvage therapy.
AB  - Among 470 patients with acquired immune deficiency syndrome and/or human
      immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance
      testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M
      mutation. The Q151M mutation was associated with younger age, lower CD4(+)
      lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens.
      By contrast, the Q151M mutation was inversely associated with lamivudine
      administration. A full reversion of the Q151M mutation was observed in 5 of 5
      patients who underwent treatment interruption after GRT. The reversion was
      followed by a response to salvage therapy in 4 (80%) of 5 patients.

PMID- 14727219
TI  - Syringe distribution to injection drug users for prevention of HIV infection:
      opinions and practices of health care providers in New York City.
AB  - The Expanded Syringe Access Demonstration Program (ESAP), which was intended to
      increase access to syringes for injection drug users (IDUs), went into effect in
      New York State on 1 January 2001. ESAP allowed prescription-authorized health
      care providers to register to distribute syringes without a prescription. In
      spring 2002, we conducted a random postal survey of 1100 providers in New York
      City to evaluate involvement in ESAP and willingness to furnish IDUs with
      syringes. Among 363 nurse practitioners, physicians, and physician assistants
      responding, 16.9% knew about ESAP, and 2.0% believed they were registered; 50.5%
      would consider distributing syringes to patients who were IDUs. Most of those
      unwilling to distribute syringes were concerned about legal and moral issues.
      More respondents agreed that providers should prescribe syringes than distribute
      syringes (41.1% vs. 22.7%; P<.0001). These results suggest that many providers
      are willing to furnish IDUs with syringes but are unaware of the current law.

PMID- 14727220
TI  - A 63-year-old man with skin eruptions.

PMID- 14727221
TI  - Short-term treatment of actinomycosis: two cases and a review.
AB  - Recommendations for prolonged penicillin treatment of actinomycosis date from the
      early antibiotic era, when patients often presented with neglected, advanced
      disease and received interrupted therapy at suboptimal dosages. This report
      describes cases of esophageal and of cervicofacial actinomycosis treated
      successfully with short-term antibiotic therapy and reviews the literature. Many
      patients are cured with <6 months of antibiotic therapy. If short-term antibiotic
      treatment is attempted, the clinical and radiological response should be closely
      monitored. Cervicofacial actinomycosis is especially responsive to brief courses
      of antibiotic treatment.

PMID- 14727222
TI  - Clinical features associated with bacteremia due to heterogeneous vancomycin
      intermediate Staphylococcus aureus.
AB  - We assessed all episodes of methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia at our hospital during a 12-month period (n=53) and compared those due
      to heterogeneous vancomycin-intermediate S. aureus (hVISA; n = 5, 9.4%) with
      those due to vancomycin-susceptible MRSA (n=48). Patients with hVISA bacteremia
      were more likely to have high bacterial load infections (P=.001), vancomycin
      treatment failure (persistent fever and bacteremia for >7 days after the start of
      therapy; P<.001), and initially low serum vancomycin levels (P=.006). These
      clinical markers of hVISA bacteremia may help focus diagnostic efforts and
      treatment.

PMID- 14727223
TI  - Nutritionally variant streptococcal infections at a University Hospital in
      Taiwan: disease emergence and high prevalence of beta-lactam and macrolide
      resistance.
AB  - From January 1993 to December 2002, 28 patients with nutritionally variant
      streptococci (NVS) infections were treated at a university hospital in Taiwan.
      Twelve (43%) of these patients had various underlying malignancies, and 7 (25%)
      had underlying valvular heart diseases. Nine patients (32%) had infective
      endocarditis, and 9 (32%) had primary bacteremia. The deaths of 7 patients (25%)
      were directly related to NVS infection. Among the 28 isolates recovered from
      these patients, 50% were not susceptible to penicillin, 33% were not susceptible
      to cefotaxime, and 93% were not susceptible to azithromycin.

PMID- 14727224
TI  - Lack of vaccinia viremia after smallpox vaccination.
AB  - Although the transmission of certain viral infections (human immunodeficiency
      virus, hepatitis B and C viruses, and West Nile virus) through donated blood
      products is well described, the risk of transmitting vaccinia virus after
      smallpox vaccination is unknown. Blood samples from patients receiving the
      smallpox vaccine were obtained before vaccination; then from one-half of the
      study group on alternate days for each of the first 10 days after vaccination;
      then from all patients on days 14 and 21 after vaccination. Samples were analyzed
      by culture, polymerase chain reaction, and antigen detection
      (electrochemiluminescence) assay for the presence of vaccinia virus. Two hundred
      and twenty samples from 28 volunteers were processed by all 3 laboratory
      detection methods and all were negative for the presence of vaccinia virus
      (confidence interval, 0%-12.3%). Viremia with vaccinia virus after smallpox
      vaccination appears to be an uncommon occurrence.

PMID- 14727225
TI  - Propionibacterium propionicus infection in chronic granulomatous disease.

PMID- 14727226
TI  - How much evidence do we have to recommend oral doxycycline for empirical
      treatment of community-acquired pneumonia?

PMID- 14727227
TI  - Utility of eosinophil count as predictor of bacteremia.

PMID- 14727228
TI  - Pyomyositis and cutaneous abscesses due to Mycobacterium avium: an immune
      reconstitution manifestation in a patient with AIDS.

PMID- 14727229
TI  - Therapy for severe histoplasmosis: what's best?

PMID- 14727230
TI  - Case study: posaconazole treatment of disseminated phaeohyphomycosis due to
      Exophiala spinifera.
AB  - A 41-year-old woman with no known immunosuppression experienced a 12-year period
      of a relapsing phaeohyphomycosis. Despite administration of multiple courses of
      therapy with standard antifungals, sustained clinical remission was not achieved.
      A partial response was seen initially with the combination of itraconazole and
      flucytosine therapy, but the patient did not respond to subsequent treatment.
      During the patient's pregnancy, the mycosis became disseminated, with
      lymphadenopathy and fever, and was considered life threatening. Despite receipt
      of parenteral amphotericin B therapy, the patient did not show a clinical
      response. After premature delivery by cesarean section, treatment with oral
      posaconazole suspension (800 mg/day) was started. The patient's condition
      improved within 1 week after initiating treatment; therapy was continued for 13
      months. During posaconazole treatment, the patient showed a complete clinical
      response, with negative results of fungal cultures.

PMID- 14727231
TI  - Mycoplasma endocarditis: two case reports and a review.
AB  - We describe 2 patients with endocarditis for whom blood cultures and cardiac
      valve cultures were repeatedly sterile. Broad-range eubacterial polymerase chain
      reaction (PCR) amplification performed on cardiac valve specimens from these 2
      patients detected DNA of Mycoplasma hominis, for one patient, and of Ureaplasma
      parvum, for the other patient. Three other cases of infective endocarditis caused
      by mycoplasmas were identified in the literature. It is important to rule out a
      diagnosis of mycoplasma endocarditis because the evolution of the disease may be
      fatal and it requires an adequate and specific antibiotic therapy.

PMID- 14727232
TI  - Microangiopathic anemia without thrombocytopenia and kidney disease in a child
      with diarrhea caused by Shiga toxin-producing Escherichia coli.
AB  - A child with a history of diarrhea presented with transient anemia,
      reticolucytosis, and red blood cell fragmentation. Blood pressure and levels of
      blood platelets, creatinine, and urea were normal, as were results of urinalysis.
      Escherichia coli harboring genes for Shiga toxin were detected in stool
      specimens. It is concluded that extraintestinal diseases caused by Shiga toxin
      producing bacteria sometimes present without any renal involvement.

PMID- 14727234
TI  - Proceedings of the 3rd International Cytoprotection Investigators' Congress. May
      15-18, 2003, Nevis, West Indies.

PMID- 14727235
TI  - Amifostine reduces radiochemotherapy-induced toxicities in patients with locally
      advanced non-small cell lung cancer.
AB  - Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small
      cell lung cancer, but can be limited by acute and late toxicities (esophagitis,
      pneumonitis, and myelosuppression). This trial investigated whether pretreatment
      with amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), a
      radioprotector, could reduce the incidence of RCT-induced acute and late
      toxicities. Between October 1997 and August 1999, 73 patients with previously
      untreated stage IIIa-IIIb non-small cell lung cancer were randomized to treatment
      with RCT alone or RCT plus amifostine (300 mg/m(2) daily intravenous infusion).
      Chemotherapy consisted of either paclitaxel (60 mg/m(2)) or carboplatin (area
      under the concentration-curve of 2) once weekly during a 5- to 6-week course of
      conventional radiotherapy given as 2 Gy daily fraction, 5 days a week to a total
      dose of 55 to 60 Gy. Esophagitis and acute lung toxicity were evaluated during
      treatment; late lung toxicity was assessed at 3 and 6 months after RCT and was
      graded from 0 to 4 according to the Radiation Therapy Oncology Group/European
      Organization for the Research and Treatment of Cancer criteria. Esophageal
      endoscopy was performed the fourth week during RCT and 1 month after the end of
      RCT. Endoscopic findings of radiation esophagitis were scored from 0 to 3. There
      was no significant difference between treatment arms in baseline patient
      characteristics. A total of 68 patients were evaluable for toxicity and efficacy
      (RCT group, n = 32; RCT plus amifostine, n = 36). The incidence of grade >or= 3
      esophagitis during RCT was significantly lower for patients receiving amifostine
      than for those receiving RCT alone (38.9% v 84.4%; P <.001). The incidence of
      grade >or= 3 acute pulmonary toxicity was also significantly reduced in
      amifostine-treated patients (19.4% v 56.3%; P =.002). At 3 months following RCT,
      patients treated with amifostine had a significantly lower incidence of
      pneumonitis than those who received RCT alone (P =.009). Endoscopic grade >or= 2
      esophagitis was observed in eight of 15 patients in the RCT group and in three of
      18 patients in the RCT plus amifostine group (P =.061). No significant
      differences in response rates were noted between patients receiving RCT with or
      without amifostine (P =.498). Amifostine is effective in reducing the incidence
      of both acute and late toxicities associated with RCT in patients with locally
      advanced non-small cell lung cancer without compromising antitumor efficacy.

PMID- 14727236
TI  - Radioprotective effect of amifostine in radiation pneumonitis.
AB  - Amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) is a member of a
      sulfhydryl-containing class of compounds that protects normal tissue and organs
      against ionizing radiation damage by scavenging radiation-induced radicals. The
      goal of this study was to assess the preclinical and clinical data on the
      protective effect of amifostine in normal organs and tissue. The current
      literature was reviewed and assessed for progress in the pathogenesis of
      radiation-induced pulmonary injury. Preclinical and clinical data on the
      protective effect of amifostine in radiation-induced lung and esophageal injuries
      were also critically assessed. Significant progress has been made in
      understanding the pathogenesis of radiation pneumonitis. Preclinical studies have
      shown strong evidence of the protective effect of amifostine in radiation-induced
      toxicities in rodents and monkeys. However, available clinical data are not
      conclusive in showing the protective effect of amifostine in radiation
      pneumonitis and esophagitis. Amifostine has been well tolerated with a low
      incidence of toxicities, which included nausea and vomiting (3% to 5%) and
      transient hypotension during intravenous infusion (7%). Preclinical data are
      promising for amifostine in protecting thoracic organs from radiation-induced
      toxicities. Studies measuring the magnitude of gain in tumor control and survival
      as a result of the enhanced protective effect of amifostine on normal tissue over
      that of tumor tissue are lacking. Such data would help in designing new
      approaches to maximize outcome. Additional well-designed phase III studies are
      necessary to confirm the clinical benefit of amifostine in minimizing radiation-
      and chemoradiation-related toxicities in patients with lung cancer.

PMID- 14727237
TI  - Amifostine: is there evidence of tumor protection?
AB  - A large body of experimental evidence suggests that amifostine (Ethyol, WR-2721;
      MedImmune, Inc, Gaithersburg, MD) is a selective cytoprotector of normal tissues.
      Nevertheless, several experimental studies, most of which were conducted in the
      early 1980s, suggest that amifostine may protect tumor tissues, although to a
      much lower degree than its protective effect on normal tissues. Based on a
      critical literature review, we conclude that any experimental evidence suggesting
      tumor protection is weak. The effects of anesthesia and hypotension on normal and
      tumor tissue oxygenation status of animals, the consequences of such events on
      amifostine activity, and the impact of this complex situation on host immunity
      and radiotherapy efficacy in the experimental setting do not reliably simulate
      the clinical setting. Analyses of radiobiologic and histologic results of the
      Canine Sarcoma Study show that, if any conclusion is to be made, amifostine
      protected normal tissues and preserved (or even enhanced) the antitumor activity
      of radiotherapy. The Ormaplatin Study clearly showed a 10-fold decreased
      concentration of platinum in tumor compared with normal tissues, and does not
      therefore support evidence of lack of amifostine selectivity. Finally, not one
      clinical study suggests tumor protection with amifostine. On the contrary, the
      majority of clinical data strongly suggest that patients who receive amifostine
      with radiotherapy and/or chemotherapy do better than controls. Rather than
      organizing large-scale, randomized clinical trials to exclude tumor protection by
      amifostine, it seems more useful to design trials that would measure amifostine
      benefits in terms of improved quality of life, tumor control, and survival rates
      in patients being treated with standard or novel chemotherapy/radiotherapy
      regimens.

PMID- 14727238
TI  - Effects of dose and schedule on the efficacy of ethyol: preclinical studies.
AB  - The chemo- and radioprotectant drug amifostine (Ethyol; MedImmune, Inc,
      Gaithersburg, MD) is approved for intravenous (IV) administration; however, the
      subcutaneous (SC) route is being explored as a practical alternative. We have
      previously reported equivalence between IV and SC administration using a rat
      model of radioprotection and active metabolite (WR-1065) tissue pharmacokinetics.
      To examine the more clinically relevant fractionated and hyperfractionated
      radiation schedules and the effects of variations in the time of amifostine
      administration, we expanded these studies to include radioprotection and
      pharmacokinetic studies of WR-1065 using multiple dosing. To measure
      radioprotection using a fractionated radioprotection model, rats were given
      amifostine over a 1-week period at various doses (25 mg/kg, 50 mg/kg, 100 mg/kg;
      or 162.5 mg/m(2), 325 mg/m(2), 650 mg/m(2), respectively) IV or SC daily 30
      minutes before exposure to 7.5 Gy/dose. Rats were fully protected from mucositis
      at the highest amifostine dose, with protection diminishing as the amifostine was
      decreased. Equivalent protection was observed whether the drug was given IV or
      SC. When the number of days of amifostine administration was reduced, protection
      was diminished. Amifostine also protected against radiation delivered using a 1
      week hyperfractionated schedule (4.5 Gy/exposure twice daily), with optimal
      protection occurring when the drug was administered bid 30 minutes before each
      exposure (50 mg/kg) or every day before the morning exposure (100 mg/kg). The
      need for daily dosing to achieve optimal radioprotection was consistent with the
      tissue pharmacokinetics of the active metabolite. We found that WR-1065 did not
      accumulate in tissues or in SC-implanted tumors when amifostine was administered
      daily for 3 weeks. In addition, tissue and tumor levels of WR-1065 declined to
      baseline 24 hours after each amifostine dose. In a monkey pharmacokinetic model,
      plasma levels of WR-1065 (characterized by a pronounced spike of WR-1065
      immediately after IV administration that was absent when the drug was given SC)
      were similar to those of humans; however, levels of WR-1065 in the tissues were
      higher 30 minutes following SC administration and were equivalent 60 minutes
      following IV or SC administration. These results suggest that maximum tissue
      levels and protection occur when amifostine is given 30 to 60 minutes before
      radiation exposure, that treatment breaks reduce the radioprotection by
      amifostine, and that protection from hyperfractionated radiation is dependent on
      amifostine dose and schedule.

PMID- 14727239
TI  - Rationale for integrating high-dose rate intraoperative radiation (HDR-IORT) and
      postoperative external beam radiation with subcutaneous amifostine for the
      management of stage III/IV head and neck cancer.
AB  - Locoregional recurrence remains a major obstacle to achieving cure of locally
      advanced head and neck cancers despite maximal resection and postoperative
      external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40%
      of high-risk resected head and neck cancer patients after standard postoperative
      EBRT. In an effort to overcome this problem, a number of strategies have been
      designed to enhance the effectiveness of radiation including concurrent
      postoperative chemoradiation, accelerated radiation schedules, incorporation of
      targeted biologic therapies, and improved radiation delivery techniques such as
      intensity modulated radiation and high-dose rate (HDR) intraoperative radiation
      therapy. Intraoperative radiation therapy (IORT) represents an important approach
      to improve outcome in head and neck cancer patients treated with definitive
      surgery. High-dose rate IORT is defined as the delivery of a single, large dose
      of radiation at the time of surgery when the tumor bed is exposed. In conjunction
      with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery
      of a large dose of radiation while the tumor bed is precisely defined, minimizing
      the risk of a geographic miss; (2) potential for subsequent dose reduction of
      EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because
      mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the
      most common long-term quality-of-life complaint, a reduction of the EBRT dose may
      provide an important benefit in reducing toxicity, especially when combined with
      the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg,
      MD). The purpose of this article is to review the rationale for integrating HDR
      IORT with a reduced dose of postoperative EBRT combined with amifostine to
      improve locoregional control and quality of life outcomes in advanced-stage
      resected head and neck cancer patients.

PMID- 14727240
TI  - Feasibility of amifostine administration in conjunction with high-dose rate
      brachytherapy.
AB  - This ongoing study was initiated to determine the feasibility of administering
      amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) with monomodal
      high-dose rate (mHDR) brachytherapy and to assess the tolerability and side
      effects of this combination. To date, 18 patients suitable for prostate implant
      brachytherapy (<or=T2aN0; prostate-specific antigen <or= 10 ng/mL; Gleason score
      <or= 6) have been treated with mHDR brachytherapy, receiving four 9-Gy fractions
      administered twice daily for 2 days. Amifostine (500 mg) is administered
      subcutaneously on the day before implant and 30 to 60 minutes before the first
      and third mHDR treatments. All 18 patients have received amifostine and
      brachytherapy as planned. Nausea was manageable with oral prochlorperazine in the
      pretreatment phase and our standard antiemesis protocol (intravenous
      promethazine, with granisetron if needed) during the implant; hypotension and
      asthenia were not problematic. During the 2-week post-treatment phase, grade 1
      cystitis occurred in eight of 18 patients; grades 1 and 2 proctitis occurred in
      six of 18 and five of 18 patients, respectively. Six patients developed urinary
      obstruction symptoms. Preliminary results support the feasibility and
      tolerability of subcutaneous amifostine in conjunction with mHDR brachytherapy.
      Total accrual goal is 50 patients to assess long-term efficacy. Additional
      studies of HDR with amifostine are planned for patients with recurrent prostate
      and gynecologic cancer.

PMID- 14727241
TI  - Amifostine and external beam radiation therapy and/or high-dose rate
      brachytherapy in the treatment of localized prostate carcinoma: preliminary
      results of a phase II trial.
AB  - Local control of carcinoma of the prostate, when treated with radiation therapy,
      is dose related. It is well documented that higher radiation doses can produce
      definitive improvement but not without an increased risk of developing
      gastrointestinal and/or genitourinary toxicities. Radioprotective agents, such as
      amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), have been proven
      to reduce radiotherapy-induced toxicities to normal tissue in patients with head
      and neck, thoracic, and pelvic tumors. Based on this information, and in an
      effort to determine the effectiveness of radioprotective agents in patients with
      prostate cancer, our institution developed a protocol involving use of amifostine
      in patients with prostate cancer treated with external beam radiation to a total
      dose of 45 Gy and/or high-dose rate brachytherapy. High-dose rate doses are 6 Gy
      times three fractions for combined therapy and 9.3 Gy times four fractions for
      the monotherapy group. To date, 13 patients have been treated, with preliminary
      results indicating an acceptably low incidence of gastrointestinal and
      genitourinary toxicities, including no acute blood pressure changes or skin
      reactions. However, there have been three cases of severe cardiopulmonary events,
      which are discussed in detail.

PMID- 14727242
TI  - Clinical trial of endorectal amifostine for radioprotection in patients with
      prostate cancer: rationale and early results.
AB  - Tolerance of the normal rectal mucosa to radiation injury limits the dose that
      can be safely delivered to the prostate gland with definitive external beam
      radiation therapy. The radioprotective agent amifostine (Ethyol; MedImmune, Inc,
      Gaithersburg, MD) is approved for intravenous use. Laboratory studies indicate
      that rectal administration results in preferential accumulation of amifostine in
      the rectal mucosa, and in clinical studies, neither free parent compound nor free
      active metabolite has been detected in the systemic circulation. This trial
      evaluates the rates of early and late rectal toxicities in patients with prostate
      cancer receiving definitive or adjuvant three-dimensional conformal external beam
      radiation therapy and concurrent daily endorectal applications of amifostine.
      Endpoints include Radiation Therapy Oncology Group acute and late toxicity
      gradings, Expanded Prostate Cancer Index Composite self-assessment
      questionnaires, and proctoscopic examinations with scoring of mucosal damage
      measured before, during, and after treatment. Eleven patients have been enrolled
      to date; 10 have completed radiotherapy and three have been followed-up to 6
      months. Two patients received 66 Gy to the prostatic bed post-prostatectomy; five
      patients received 74 Gy and three received 76 Gy to the prostate gland. In all
      patients, daily fractionation was 2 Gy, and 1 g of amifostine (50 mg/mL in 20 mL
      reconstituted saline) was administered endorectally 40 minutes before radiation
      delivery. Daily endorectal administration was well tolerated. To date, six
      patients have experienced grade 2 (Radiation Therapy Oncology Group) acute
      toxicities, all but one because of frequent bowel movements relieved by
      loperamide. The initial trial will proceed until 18 patients are accrued, at
      which time an interval evaluation of both early and late toxicity endpoints will
      be conducted.

PMID- 14727244
TI  - Aggressive multimodality therapy for patients with locally advanced esophageal
      cancer: is there a role for amifostine?
AB  - Most patients with locally advanced esophageal cancer die from their disease,
      despite complete surgical extirpation of tumor or institution of aggressive,
      multimodality treatment. Nevertheless, a favorable trend emerging in the
      management of such patients is that "more therapy is better." This review
      describes several studies indicating that aggressive, combined-modality therapy
      provides a survival advantage for patients with locally advanced esophageal
      cancer. An ongoing North Central Cancer Treatment Group trial further capitalizes
      on the concept of "more is better," and tests subcutaneous amifostine (Ethyol, WR
      2721; MedImmune, Inc, Gaithersburg, MD) to balance the need for aggressive
      therapy with the need to mitigate associated toxicity.

PMID- 14727243
TI  - Cytoprotection/radioprotection with amifostine: potential role in cervical cancer
      and early findings in the Radiation Therapy Oncology Group C-0116 trial.
AB  - Concurrent cisplatin-based chemoradiation therapy is now considered the standard
      treatment for locally advanced cervical carcinoma. Available data also suggest
      that combined-modality therapy improves outcome compared with radiation therapy
      alone in disease with positive para-aortic lymph nodes. However, radiation
      therapy alone is associated with significant toxicity in cervical cancer, and
      toxicity is increased with chemoradiation therapy. The
      cytoprotectant/radioprotectant agent amifostine (Ethyol; MedImmune, Inc,
      Gaithersburg, MD) has been found to reduce toxicities associated with cisplatin,
      radiation, and combined modality approaches in the treatment of several tumor
      types. The limited available data on the use of amifostine in patients with
      cervical or pelvic cancers indicate a benefit in reducing chemoradiation
      toxicity, although cisplatin regimens used in the early investigations in
      cervical cancer are no longer considered optimal. In the Radiation Therapy
      Oncology Group C-0116 phase I/II trial, patients with cervical cancer with
      positive para-aortic or high common iliac nodes are to receive extended-field
      radiation and intracavitary brachytherapy plus weekly cisplatin in the first part
      of the study; in the second part of the trial, patients are also to receive
      amifostine. The trial should provide important information on the potential for
      adjunctive amifostine use in chemoradiation therapy for cervical cancer.

PMID- 14727245
TI  - The effect of oral mucositis on morbidity and mortality in bone marrow
      transplant.
AB  - Oral mucosal ulceration is a frequent complication in bone marrow
      transplantation, resulting from epithelial injury caused by cytotoxic
      chemotherapy and radiation conditioning, as well as from pre-existing infection.
      Oral mucositis causes pain, interferes with patient nutrition, and can lead to
      systemic infection and other complications that increase patient morbidity and
      mortality; this complication also markedly increases the expense of bone marrow
      transplantation. A variety of interventions have been assessed for preventing
      oral mucositis or reducing the severity of mucositis and its sequelae. These
      include meticulous pretransplantation and ongoing mouth care, calcium phosphate
      solution, near-infrared light and lower-energy laser treatment, interleukin-11,
      sucralfate, oral glutamine, granulocyte-macrophage colony-stimulating factor
      rinse, tretinoin, and keratinocyte growth factor; particularly promising results
      have been observed with use of the cytoprotectant/radioprotectant agent
      amifostine. Reduction in the severity and duration of oral mucositis and its
      sequelae in patients undergoing bone marrow transplantation can have a
      substantial impact on morbidity and mortality and cost of care. Further
      systematic evaluation of approaches to prevention and management of oral
      mucositis is necessary to define optimal strategies in the transplantation
      setting.

PMID- 14727246
TI  - Phase II randomized study of concomitant chemoradiation using weekly
      carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients
      with newly diagnosed locally advanced squamous cell carcinoma of the head and
      neck.
AB  - The treatment of head and neck cancer continues to evolve. The recent use of
      aggressive chemoradiotherapy protocols has resulted in significant morbidity
      involving mucositis, dysphagia, and a higher rate of feeding tube dependency. We
      have initiated a randomized phase II study with concomitant chemoradiotherapy
      with or without subcutaneous amifostine (Ethyol, WR-2721; MedImmune, Inc,
      Gaithersburg, MD). This article presents a detailed background, rationale, and
      endpoints for this study and discusses future directions in the treatment of head
      and neck cancer.

PMID- 14727247
TI  - Docetaxel with concurrent radiotherapy in head and neck cancer.
AB  - Recent studies in the treatment of head and neck cancer suggest that combined
      chemoradiation is superior to radiation alone with regard to local-regional
      control. Agents that have shown activity as radiosensitizers include platinum
      agents and taxanes. Docetaxel is a semisynthetic taxane that affects polymerized
      tubulin both to promote microtubule formation and to inhibit its disassembly. As
      a single agent, docetaxel shows significant antitumor activity in head and neck
      cancer in the neoadjuvant setting. Docetaxel also exhibits potent
      radiosensitizing capability. Because docetaxel is a phase-specific agent,
      frequent administration of docetaxel offers the potential for enhancement of
      radiosensitization. Current trials are exploring the optimal dose and schedule of
      administration of docetaxel with concurrent radiotherapy in patients with head
      and neck cancer.

PMID- 14727248
TI  - Ongoing prospective multicenter safety study of the cytoprotectant amifostine
      given subcutaneously: overview of trial design.
AB  - The study is a prospective, open-label, multicenter safety study designed to
      identify treatment-related side effects of amifostine (Ethyol, WR-2721;
      MedImmune, Inc, Gaithersburg, MD) administered as a subcutaneous injection for
      the prevention of radiation-induced toxicities. More than 100 patients (68 males,
      33 females; median age, 64 years) received 500 mg of amifostine by subcutaneous
      injection before daily radiation therapy. Four types of targeted adverse events
      were examined as to their occurrence and possible relationship with amifostine.
      These adverse events included nausea/vomiting, local skin reactions, skin rashes,
      and hypotension.

PMID- 14727249
TI  - Pilot study of subcutaneous amifostine in patients undergoing postoperative
      intensity modulated radiation therapy for head and neck cancer: preliminary data.
AB  - The major salivary glands produce about 90% of salivary secretions; the minor
      salivary glands produce the remainder. Standard conventional radiation therapy
      for advanced oropharyngeal tumors typically involves administering high radiation
      dose to the major salivary glands bilaterally. In most cases, this causes a
      marked reduction in oral saliva output. Xerostomia is the most prevalent late
      side effect of radiation for head and neck malignancies and is cited by patients
      as the major cause of decreased quality of life. The degree of xerostomia has
      been reported to depend on the radiation dose and salivary gland volume
      irradiated. Several studies show dose volume response relationships in the
      salivary glands, suggesting the possibility of significant improvement in saliva
      production post radiation as well as quality of life if radiation techniques can
      spare the salivary glands. In recent years, conformal radiation techniques have
      evolved, which may allow radiation of tumor targets in the head and neck area
      while sparing substantial portions of salivary glands. It has been shown that in
      using these techniques, adequate irradiation of the targets while sparing major
      salivary glands is feasible. Early clinical experience showed substantial sparing
      of salivary flow following radiation and suggested an improvement of tumor
      control and of xerostomia over that achieved with standard radiation techniques.
      We hypothesize that the addition of a radioprotector may further improve salivary
      function over that obtained with intensity modulated radiation therapy alone. To
      test this hypothesis, we initiated a pilot clinical trial whose principal
      objective is to compare measurements of unstimulated and stimulated salivary flow
      rates 6 months after intensity modulated radiation therapy plus amifostine
      (Ethyol; MedImmune, Inc, Gaithersburg, MD) (study patients) with those obtained
      in historical controls treated with intensity modulated radiation therapy alone.

PMID- 14727250
TI  - Toxicity profile of intensity-modulated radiation therapy for head and neck
      carcinoma and potential role of amifostine.
AB  - Organ function preservation in patients with head and neck cancer can be achieved
      by intensity-modulated radiation therapy (IMRT). Much of the work on the physics
      of IMRT has been done for currently available IMRT systems. However, clinical
      data remain scarce. Before IMRT is accepted as a standard of care, more
      comprehensive clinical data on the outcomes of IMRT are needed to substantiate
      its superiority and advantages over conventional modes of radiotherapy.
      Concomitant chemoradiation and altered fractionation schemes improve local
      regional control, but at the cost of increased toxicity. This article presents a
      3-year update of the toxicity profile and therapeutic outcomes of 126 patients
      with head and neck carcinoma treated with IMRT. An ongoing trial of concomitant
      chemotherapy and IMRT with subcutaneous amifostine (Ethyol, WR-2721; MedImmune,
      Inc, Gaithersburg, MD) for organ function preservation is also discussed.

PMID- 14727253
TI  - Thrombotic thrombocytopenic purpura: advances in pathophysiology, diagnosis, and
      treatment--introduction.

PMID- 14727254
TI  - von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe, occlusive, microvascular
      "thrombotic microangiopathy" characterized by systemic platelet aggregation,
      organ ischemia, profound thrombocytopenia, and erythrocyte fragmentation. Failure
      to degrade "unusually large" (UL) von Willebrand factor (VWF) multimers as they
      are secreted from endothelial cells probably causes most cases of familial TTP,
      acquired idiopathic TTP, thienopyridine-related TTP, and pregnancy-associated
      TTP. The emphasis in this review is the pathophysiology of familial and acquired
      idiopathic TTP. In each of these entities, there is a severe defect in the
      function of a plasma enzyme, VWF-cleaving metalloprotease (ADAMTS-13), that
      normally cleaves hyper-reactive ULVWF multimers into smaller and less adhesive
      VWF forms. In familial TTP, mutations in the ADAMTS13 gene cause absent or
      severely reduced plasma VWF-cleaving metalloprotease activity. Acquired
      idiopathic TTP, in contrast, is the result in many patients of the production of
      autoantibodies that inhibit the function of ADAMTS-13. Established, evolving, and
      some of the unresolved issues in TTP pathophysiology will be summarized.

PMID- 14727255
TI  - Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells.
AB  - When histamine-stimulated endothelial cells are perfused with platelets in
      buffer, the platelets form long beads-on-a-string structures on the surface of
      the cells. The strands connecting the platelets are composed of ultralarge
      multimers of von Willebrand factor (ULVWF) and can be rapidly cleaved when
      perfused with normal plasma or purified ADAMTS-13 metalloprotease, but not with
      plasma from patients with either congenital or acquired thrombotic
      thrombocytopenic purpura (TTP). These ULVWF strings anchor to the surface of the
      endothelial cell at least partly through P-selectin, as their formation is
      prevented by either soluble P-selectin or P-selectin antibodies. They are also
      able to support the attachment of beads coated with ADAMTS-13. The
      metalloprotease binds to both the A1 and A3 domains of VWF, the latter with
      higher affinity. This attachment docks the enzyme close to its substrate site
      within the A2 domain. We propose that attachment of newly released ULVWF to the
      endothelial cell surface facilitates its cleavage by ADAMTS-13 by allowing
      tensile force to be applied to the A2 domain, thereby exposing the ADAMTS-13
      cleavage site.

PMID- 14727256
TI  - Expression and characterization of recombinant human ADAMTS-13.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe disease associated with
      unusually large, hemostatically hyperactive von Willebrand factor (VWF) and
      severe deficiency in ADAMTS-13, the protease responsible for the proteolytic
      degradation of VWF in plasma. ADAMTS-13 prevents inappropriate microvascular
      platelet aggregation by cleaving VWF between Tyr1605 and Met1606 thereby
      producing dimers of 176 kd and 140 kd and smaller multimers. Identification of
      the ADAMTS13 gene and cloning of the corresponding cDNA allowed for the
      application of recombinant techniques, such as genetic engineering of ADAMTS13
      cDNA, cell culture expression, and in vitro activity studies to analyze the
      functional relationship between ADAMTS-13 and the pathophysiology of ADAMTS-13
      deficiency. In vitro expression and characterization of recombinant ADAMTS-13
      (rADAMTS-13) clearly established that ADAMTS-13 is deficient in congenital TTP
      and inhibited in acquired TTP. Recent studies have contributed greatly to our
      current understanding of the molecular mechanism leading to congenital and
      acquired TTP. Apart from being a useful tool, availability of rADAMTS-13 raised
      the prospect of developing a recombinant substitution therapy to improve TTP
      treatment and allowing present diagnostic assays to be simplified. Here we report
      on recent advances in cell culture expression and functional characterization of
      human rADAMTS-13.

PMID- 14727257
TI  - Genetic defects leading to hereditary thrombotic thrombocytopenic purpura.
AB  - In patients with thrombotic thrombocytopenic purpura (TTP), unusually large
      multimers of von Willebrand factor (VWF) circulate in the plasma. This is caused
      by a functional deficiency of VWF-cleaving protease, ADAMTS-13. Although TTP
      usually occurs as an acquired form due to autoantibodies against ADAMTS-13, the
      condition may be inherited in an autosomal recessive fashion. Thus far, genomic
      DNA from 23 patients with hereditary TTP and their families has been analyzed and
      33 causative mutations identified in the ADAMTS13 gene: 19 missense, five
      nonsense, five frameshift, and four splice mutations. Common missense
      polymorphisms have been also found, one of which significantly reduces ADAMTS-13
      activity. No cases have been found without mutations in the ADAMTS13 gene,
      suggesting that genetic defects in ADAMTS13 are the dominant cause of hereditary
      TTP. Further analysis may reveal the genetic background associated with acquired
      TTP and other thrombotic diseases.

PMID- 14727258
TI  - Assays of ADAMTS-13 activity.
AB  - Various assays for determination of ADAMTS-13 activity in plasma have been
      developed, all comprising two steps. The first step consists of proteolyzing a
      substrate by ADAMTS-13. Substrates were either exogenous von Willebrand factor
      (VWF) (purified from human plasma concentrates or recombinant VWF [rVWF]),
      purified VWF fragments, or endogenous VWF (from the tested plasma sample). All
      assays required a step in which substrate unfolding is performed using either
      urea or guanidine. Test plasmas were used at various dilutions and ADAMTS-13 was
      activated in most cases by divalent cations. The second step consists of
      quantifying the digestion products or the residual VWF remaining after
      proteolysis. Cleavage of VWF was thus estimated using electrophoresis (generation
      of proteolytic fragments or decrease of the size of multimers), functional
      methods (decrease of the collagen binding activity or of ristocetin cofactor
      activity), or immunological methods (enzyme-linked immunosorbent assay [ELISA] or
      immunoradiometric assay (IRMA) using selected monoclonal antibodies to VWF).
      Since 1998, all of these assays have been used to demonstrate the relevance of a
      deficient ADAMTS-13 activity in thrombotic thrombocytopenic purpura (TTP).
      However, improvements are required, as these methods remain cumbersome, time
      consuming, and too remote from physiology to be routinely helpful for rapid
      laboratory diagnosis.

PMID- 14727259
TI  - Plasma therapy in thrombotic thrombocytopenic purpura: review of the literature
      and the Bern experience in a subgroup of patients with severe acquired ADAMTS-13
      deficiency.
AB  - Based on clinical studies daily plasma exchange (PE) has become the first-choice
      therapy for thrombotic thrombocytopenic purpura (TTP) since 1991. Recent findings
      may explain its effectiveness, which particularly may include supply of ADAMTS-13
      and removal of anti-ADAMTS-13 autoantibodies and unusually large von Willebrand
      factor (VWF) multimers. The most preferable PE regimens as well as replacement
      fluids are discussed and treatment-related adverse reactions are summarized.
      Proposals for a potential reduction of their frequency and for improvement of
      treatment efficiency are given. These suggestions are partially based on the
      experience of our institution in adult patients with severe ADAMTS-13 deficiency
      (<5% activity), and include (1) continuous calcium-gluconate infusion during PE
      in order to reduce citrate-related adverse reactions; (2) the evaluation of
      solvent/detergent-treated (S/D) plasma as replacement fluid in order to reduce
      adverse events due to fresh frozen plasma (FFP); (3) the evaluation of
      immunoadsorption in order to increase procedural efficiency in autoantibody
      removal; and (4) the substitution of ADAMTS-13 by means of recombinant drug
      instead of plasma.

PMID- 14727260
TI  - The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP
      HUS) Registry: a community perspective of patients with clinically diagnosed TTP
      HUS.
AB  - The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP
      HUS) Registry enrolls all consecutive patients for whom plasma exchange treatment
      is requested for clinically diagnosed TTP-HUS within a defined geographic region.
      During 14.5 years, from January 1, 1989 until June 30, 2003, 301 patients have
      been enrolled; follow-up is complete on 300 patients. Clinical categories have
      been designated based on associated conditions and potential etiologies;
      presenting features and clinical outcomes have been defined to allow comparisons
      between groups. ADAMTS-13 activity was measured on 142 (88%) of 161 consecutive
      patients enrolled from 1995 to 2001. Only 13% of all patients, and 33% of
      patients with idiopathic TTP-HUS, had severe ADAMTS-13 deficiency (<5% activity).
      The presenting features and clinical outcomes of patients with severe ADAMTS-13
      deficiency were heterogeneous and not distinct from patients without severe
      ADAMTS-13 deficiency. These data suggest that severe ADAMTS-13 deficiency does
      not detect all patients who may be appropriately diagnosed with TTP-HUS and who
      may respond to plasma exchange treatment. Prospective data from consecutive
      patients are essential to translate new observations on pathogenesis into
      improved patient care.

PMID- 14727261
TI  - The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome.
AB  - A total of 290 Japanese patients with thrombotic thrombocytopenic purpura
      hemolytic uremic syndrome (TTP-HUS) were analyzed with respect to ADAMTS-13
      activity and its inhibitor. Twenty-one patients (17 families) had Upshaw-Schulman
      syndrome, and 12 patients (six families) had familial HUS of undetermined
      etiology. The number of patients with acquired HUS and TTP was 44 and 213,
      respectively. In acquired TTP, patients with severe deficiency of ADAMTS-13
      activity secondary to the presence of an inhibitor were high responders to plasma
      exchange, but others were low responders to plasma exchange. The former patients
      were associated with "idiopathic" TTP, drugs, and pregnancy, and the latter
      patients with malignancy and stem cell transplantation. Patients with autoimmune
      disease-associated TTP fit into both groups.

PMID- 14727262
TI  - von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the
      diagnosis of thrombotic microangiopathies: the Swiss experience.
AB  - Severe deficiency of von Willebrand factor (VWF)-cleaving protease (ADAMTS-13)
      activity (<5% of normal) is a specific finding for acute idiopathic thrombotic
      thrombocytopenic purpura (TTP), a disorder that presents as thrombocytopenia,
      microangiopathic hemolytic anemia, and often organ dysfunction such as
      neurological disturbances or renal failure, and fever. Between January 2001 and
      July 2003, ADAMTS-13 activity was determined in plasma samples of 396 consecutive
      patients referred to our laboratory for diagnostic purposes. Plasma samples with
      ADAMTS-13 activity less than 5% were in addition tested for the presence of
      inhibitory antibodies. Patients were assigned to 10 predefined clinical
      categories according to information provided by the referring clinician:
      thrombotic microangiopathy (TMA) not further specified; neoplasia- or
      chemotherapy-associated TMA; TMA following hematopoietic stem cell
      transplantation; TMA with additional/alternative disorder; idiopathic TTP;
      hemolytic-uremic syndrome (HUS) not specified; HUS with diarrhea prodrome
      (D+HUS); atypical HUS; other hematological disorder; and no clinical information
      available. Severe ADAMTS-13 deficiency was found in 69 (17%) patients, including
      42 with acquired idiopathic TTP, either at initial presentation or at relapse, 14
      with confirmed or suspected hereditary TTP, 10 with TMA not further specified,
      two with neoplasia- or chemotherapy-associated TMA, and one in continued clinical
      remission 3.4 years after splenectomy for plasma-refractory TTP. Forty-three
      (62%) patients with ADAMTS-13 activity less than 5% displayed inhibitory
      antibodies. Severe ADAMTS-13 deficiency was found in 60% of patients diagnosed
      with acute idiopathic TTP, but in none of 130 patients diagnosed with HUS or in
      any of the 14 patients with hematopoietic stem cell transplantation-associated
      TMA. Thus, plasma ADAMTS-13 activity less than 5% does not identify all patients
      clinically diagnosed with TTP, and severe ADAMTS-13 deficiency is not invariably
      associated with clinical manifestations of microvascular platelet clumping.

PMID- 14727263
TI  - Severe ADAMTS-13 deficiency in childhood.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic disorder
      with high morbidity and significant mortality. The primary form of TTP is caused
      by severe deficiency, acquired or hereditary, of the von Willebrand factor
      cleaving protease (VWF-CP), ADAMTS-13. Because TTP occurs less frequently in
      children, general pediatricians are not well informed about the spectrum of
      clinical symptoms and altered laboratory values, increasing the risk of
      nondiagnosis and possible fatal outcome. If renal involvement is present, the
      condition can easily be misdiagnosed as hemolytic-uremic syndrome (HUS). We
      present a case series of children with severe VWF-CP deficiency with emphasis on
      the clinical heterogeneity responsible for misdiagnosis and inappropriate
      treatment. The inherited form may involve onset of symptoms ranging from isolated
      thrombocytopenia to the full clinical picture characteristic of classical TTP.
      The most common assumed diagnoses of oligosymptomatic forms are immune
      thrombocytopenia (ITP) and Evans syndrome, respectively. Accordingly, this
      article is directed towards pediatricians on neonatal and intensive care units,
      as well as their colleagues specializing in nephrology, hematology, and
      neurology.

PMID- 14727269
TI  - Continuous perineural infusions at home: narrowing the focus.

PMID- 14727270
TI  - Restricting spinal block to the operative side: why not?

PMID- 14727271
TI  - Exploring the subdural space.

PMID- 14727272
TI  - Interscalene perineural ropivacaine infusion:a comparison of two dosing regimens
      for postoperative analgesia.
AB  - BACKGROUND AND OBJECTIVS: A continuous interscalene nerve block with a perineural
      infusion of ropivacaine 0.2% at 8 mL/h has been shown to provide potent analgesia
      following moderately painful shoulder surgery. However, this high basal rate
      limits infusion duration for ambulatory patients who must carry the local
      anesthetic reservoir. We undertook this investigation to determine if the basal
      rate of an interscalene perineural ropivacaine infusion could be decreased by 50%
      with a concurrent 200% increase in patient-controlled bolus dose without
      compromising infusion benefits in ambulatory patients undergoing moderately
      painful orthopedic shoulder surgery. METHODS: Preoperatively, patients (n = 24)
      received an interscalene perineural catheter and nerve block. Intraoperatively,
      patients received a standardized general anesthetic. Postoperatively, patients
      were discharged home with a portable infusion pump delivering ropivacaine 0.2%
      (500 mL reservoir) with a basal rate of 8 mL/h and a 2 mL patient-controlled
      bolus available each hour ("8/2" group, n = 12) or a 4 mL/h basal rate and 6 mL
      bolus dose ("4/6" group, n = 12), delivered in a randomized, double-blinded
      manner. RESULTS: Patients in the 4/6 group had higher baseline pain scores only
      on postoperative day (POD) 2 (P =.011). However, these patients also experienced
      an increase in breakthrough pain incidence (5.8 boluses/d v 3.2, P =.035) and
      intensity ("worst" pain = 8/10 v 4/10, P <.05), sleep disturbances (2.0 v 0.0, P
      <.001), and a decrease in analgesia satisfaction (8 v 10, P =.003). Patients in
      the 8/2 group exhausted their local anesthetic reservoirs after a median of 61
      hours, while the 4/6 group had a median of 131 mL remaining at infusion
      discontinuation after a median of 75 hours (P <.001). CONCLUSIONS: Following
      moderately painful ambulatory shoulder surgery, decreasing an interscalene
      perineural ropivacaine 0.2% basal rate from 8 to 4 mL/h provides similar baseline
      analgesia and lengthens infusion duration, but compromises other infusion
      benefits.

PMID- 14727273
TI  - A low-dose bupivacaine: a comparison of hyperbaric and hypobaric solutions for
      unilateral spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: The injection of small doses of local anesthetic
      solutions through pencil-point directional needles and maintaining the lateral
      decubitus position for 15 to 30 minutes after the injection have been suggested
      to facilitate the unilateral distribution of spinal anesthesia. We evaluated the
      effects of hypobaric and hyperbaric bupivacaine in attempting to achieve
      unilateral spinal anesthesia for patients undergoing lower limb orthopedic
      surgery. METHODS: Fifty patients were randomly allocated into 2 groups to receive
      either 1.5 mL hyperbaric bupivacaine 0.5% (7.5 mg; n = 25) or 4.2 mL hypobaric
      bupivacaine 0.18% (7.5 mg; n = 25). Drugs were administered at the L3-4
      interspace with the patient in the lateral position. Patients remained in this
      position for 15 minutes before turning supine for the operation. Spinal block was
      assessed by pinprick and modified Bromage scale on both sides. RESULTS:
      Unilateral spinal block was observed in 20 patients in the hyperbaric group (80%)
      and in 19 patients in the hypobaric group (76%) while in the lateral position.
      However, 15 minutes after patients were turned supine, unilateral spinal
      anesthesia decreased to 68% of cases in the hyperbaric group and 24% of cases in
      the hypobaric group (P <.05). The motor block was more intense during the first 5
      and 10 minutes (P <.05), but at the end of operation there was no difference
      between the groups. The hemodynamic changes were similar between the groups.
      CONCLUSION: As a result, unilateral spinal anesthesia with hyperbaric and
      hypobaric bupivacaine provided a rapid motor and sensory recovery and good
      hemodynamic stability, but more unilateral spinal block was achieved in patients
      in the hyperbaric group when compared with patients in the hypobaric group.

PMID- 14727274
TI  - A comparison of lateral popliteal versus lateral midfemoral sciatic nerve
      blockade using ropivacaine 0.5%.
AB  - BACKGROUND AND OBJECTIVES: The midfemoral approach to the sciatic nerve (MF) is a
      new technique that has been used for postoperative analgesia after knee surgery.
      The aim of the present study was to compare efficacy, performance time, and
      patient acceptance of the midfemoral approach to that of the lateral approach at
      the level of the popliteal fossa (popliteal block [PB]). METHODS: Sixty-three
      patients were enrolled in this prospective, randomized study. Thirty-two patients
      received a lateral sciatic nerve block (group PB) and 31 patients a midfemoral
      block (group MF). Ropivacaine 0.5% (30 mL) was used in both groups. RESULTS: The
      quality of nerve blockade was comparable in both groups. Onset of sensory block
      for peroneal and tibial nerves was significantly shorter in group MF than in
      group PB, 5 (1-20) minutes and 5 (1-20) minutes versus 10 (1-40) minutes and 10
      (1-45) minutes, respectively. Onset of motor block in both territories was also
      shorter in group MF compared with PB, 6 (2-35) minutes and 5 (2-55) minutes
      versus 15 (2-60) minutes and 15 (2-60) minutes, respectively (P <.05). There was
      no difference in duration of sensory and motor blockade, 16 (7-32) hours versus
      16 (6-43) hours and 16 (8-32) hours versus 16 (6-25) hours. There was no
      significant difference between both groups with respect to difficulty of nerve
      block performance. Patient discomfort during needle puncture was also similar.
      CONCLUSIONS: The midfemoral approach to the sciatic nerve for ankle and foot
      surgery resulted in a reliable anesthetic, comparable to that of the lateral
      popliteal approach. This technique is simple, safe, and provides postoperative
      analgesia as effective as that obtained with the lateral approach.

PMID- 14727275
TI  - Efficacy of three doses of ketamine with bupivacaine for caudal analgesia in
      pediatric inguinal herniotomy.
AB  - BACKGROUND AND OBJECTIVES: Ketamine administered systemically is a potent
      analgesic at subanesthetic plasma concentrations. Addition of ketamine to
      bupivacaine for caudal epidural block significantly prolongs the duration of
      postoperative analgesia. The purpose of this prospective, randomized double-blind
      study is to identify the optimal dose of ketamine that produces the maximum
      duration of caudal analgesia with minimal adverse effects as an adjuvant to
      bupivacaine for caudal epidural block. METHODS: Sixty children, aged 6 months to
      10 years, undergoing inguinal herniotomy were allocated randomly to receive 1 of
      3 solutions for caudal epidural block. Group 1 received 0.75 mL/kg of bupivacaine
      0.25% with preservative-free ketamine 0.25 mg/kg, group 2 received 0.75 mL/kg of
      bupivacaine 0.25% with ketamine 0.5 mg/kg, and group 3 received 0.75 mL/kg of
      bupivacaine 0.25% with ketamine 1 mg/kg. Postoperative pain was assessed using
      the All India Institute of Medical Sciences pain discomfort scale. Rescue
      analgesia in the form of pethidine 1 mg/kg intramuscularly was administered when
      this score exceeded 4. RESULTS: The mean duration of caudal analgesia was 8.8
      hours in group 1 compared with 22.1 hours in group 2 (P <.001) and 25.2 hours in
      group 3 (P <.001). Supplemental analgesia requirements with pethidine were
      significantly less in group 2 (4 subjects) and group 3 (no subject) when compared
      with group 1 (18 subjects). There were no differences between the groups in the
      incidence of motor blockade, urinary retention, emesis, or sedation. Group 3 had
      a significantly higher incidence of behavioral side effects such as odd behavior,
      agitation, or restlessness than groups 1 and 2. CONCLUSIONS: The optimal dose of
      ketamine in our study was 0.5 mg/kg added to 0.75 mL/kg bupivacaine 0.25% for
      caudal epidural block without an increase in side effects.

PMID- 14727276
TI  - Thigh rotation and the anterior approach to the sciatic nerve: a magnetic
      resonance imaging study.
AB  - BACKGROUND AND OBJECTIVES: The anterior approach to the sciatic nerve block may
      be associated with a high failure rate because the nerve lies posterior to the
      lesser trochanter of the femur at the level of needle insertion. However,
      previous work using cadavers demonstrated that internal rotation of the leg
      renders the nerve more accessible to the anterior approach. METHODS: Ten
      volunteers consented to undergo magnetic resonance imaging. Markers were placed
      on the surface where a needle would have been inserted for an anterior approach
      to the sciatic nerve. Three scans were then performed: the first with both legs
      in the neutral position, the second with maximal bilateral internal rotation at
      the hip, and the third with maximal bilateral external rotation at the hip.
      RESULTS: Examination of the scans by a consultant radiologist showed that, as the
      thigh is rotated, the number of scans showing an unobstructed needle passage from
      the skin marker to the sciatic nerve rate increased from 5% in external rotation
      to 85% in internal rotation. The number of times the needle path passed through
      femoral neurovascular bundle also fell from 55% in external rotation to 15% in
      internal rotation. CONCLUSIONS: The results confirm that, as the thigh is moved
      from an externally to an internally rotated position, the sciatic nerve becomes
      more accessible by the anterior approach at the level of the lesser trochanter,
      and the risk of femoral artery or nerve puncture is reduced but not eliminated.

PMID- 14727277
TI  - The neurobiology of infant pain: development of excitatory and inhibitory
      neurotransmission in the spinal dorsal horn.

PMID- 14727278
TI  - Accidental subdural injection during attempted lumbar epidural block may present
      as a failed or inadequate block: radiographic evidence.
AB  - BACKGROUND AND OBJECTIVES: Until now, case reports after accidental subdural
      injection during attempted epidural block have usually described extensive
      neuraxial blocks with a delayed onset, after low doses of local anesthetic, with
      a characteristic radiographic appearance on contrast injection. Our radiographic
      investigation of atypical "epidural" blocks has revealed that subdural injection
      may go unrecognized clinically and may be a cause of inadequate blocks. The
      mechanism is explored. CASE REPORTS: A radiographic study of 35 cases of atypical
      or inadequate blocks for cesarean delivery has unexpectedly revealed four
      instances of subdural contrast injection. On imaging, only localized posterior
      spread of subdural contrast was detected in these 4 cases, unlike the more
      widespread distribution previously reported after extensive neuraxial blocks.
      Recent findings on the ultrastructure of the subdural space are reviewed and
      related to the new clinical findings, which include inadequate blocks and pain
      developing on postoperative reinjections. CONCLUSIONS: Accidental subdural
      injection may now be added to the list of causes of failed or inadequate
      "epidural" block. Clinicians should be aware of the diagnosis of a possible
      subdural injection, if a poor quality block with restricted spread and slow onset
      is associated with pain on postoperative reinjection of the catheter.

PMID- 14727279
TI  - Anesthesia and analgesia for colon surgery.

PMID- 14727280
TI  - Regional anesthesia in a very low-birth-weight neonate for a neurosurgical
      procedure.
AB  - BACKGROUND AND OBJECTIVES: Peripheral nerve blocks can be successfully utilized
      in infants for neurosurgical procedures. Our objective was utilizing a series of
      peripheral nerve blocks for a neurosurgical procedure in a very low-birth-weight
      neonate. CASE REPORT: We report the use of supraorbital, great auricular, and
      greater occipital nerve block in a very low-birth-weight neonate (700 g) who was
      scheduled for a neurosurgical procedure. DISCUSSION: We were able to successfully
      utilize peripheral nerve blocks and were able to blunt physiologic responses to
      surgical stress without compromising hemodynamic stability using high-dose
      opioids.

PMID- 14727281
TI  - Misplacement of a psoas compartment catheter in the subarachnoid space.
AB  - BACKGROUND AND OBJECTIVES: This case report describes an unusual cause of
      misplacement of an indwelling catheter in the subarachnoid space after primary
      psoas compartment block in a patient undergoing total knee arthroplasty. CASE
      REPORT: A 67-year-old woman presenting for total knee joint replacement received
      a combination of continuous psoas compartment block and sciatic nerve block.
      Neurostimulation and additional ultrasound guidance were used for identification
      of the lumbar plexus. After elicitation of a quadriceps motor response, a
      negative aspiration test, and an uneventful test dose, 20 mL ropivacaine 0.375%
      and 20 mL mepivacaine 1% were injected. Despite difficult ultrasound conditions
      because of intestinal air, local anesthetic spread was observed paravertebrally
      at the medial border of the psoas muscle as usual. A catheter was then advanced 7
      cm through the insulated directional puncture needle. An additional sciatic nerve
      block was performed by using Labat's approach. Ten minutes after injection
      unilateral sensory block was noted and surgery was started. After uneventful
      surgery, bilateral sensory block to the T4 level and complete motor block in both
      lower limbs was detected. A second aspiration test was negative, and an epidural
      block was suspected. For verification of the catheter tip location, a computed
      tomography scan with contrast dye was performed revealing catheter placement in
      the subarachnoid space. The catheter was removed and showed a kink about 7 cm
      from the tip. After regression of the neuraxial block, lumbar plexus block
      persisted for another 2 hours. CONCLUSION: An additional test dose via the
      catheter is recommended if the indwelling catheter is inserted after injection of
      the local anesthetics through the puncture needle. If epidural anesthesia occurs,
      an x-ray of the catheter is advisable because negative aspiration via catheter
      does not rule out subarachnoid catheter location.

PMID- 14727282
TI  - Lower lobe collapse during continuous interscalene brachial plexus local
      anesthesia at home.
AB  - OBJECTIVES: We report a case of pulmonary left lower lobe collapse following an
      interscalene local anesthetic infusion administered at home. This case highlights
      the need for patient education and postoperative communication. CASE REPORT:
      report A 52-year-old male patient presented for a rotator cuff repair. He was a
      chronic tobacco abuser with a history of occasional chest pain of unexplained
      cause. An interscalene catheter was placed preoperatively and surgery was
      performed under a combination of an interscalene block and a general anesthetic.
      An infusion of 0.2% ropivacaine was started via the interscalene catheter
      postoperatively and continued at home following his discharge from the hospital
      on the third postoperative day. Within 24 hours of discharge, he was readmitted
      to the hospital after complaining of chest pain and dyspnea. The patient was seen
      in the emergency department by nonanesthesiologists who were not familiar with
      the potential for interscalene blocks to cause diaphragmatic paresis.
      CONCLUSIONS: Good communication must be maintained with the patient at all times.
      Doctors from other specialties may be unaware of the potential complications of
      an interscalene block.

PMID- 14727283
TI  - Paresthesia: what causes this sensory phenomenon?

PMID- 14727285
TI  - Infectious complications.

PMID- 14727286
TI  - Barbiturate hyperalgesia revisited.

PMID- 14727287
TI  - A new approach to the supraclavicular block.

PMID- 14727288
TI  - Fluoroscopy in the operating room as an aid to determine catheter tip position
      for continuous peripheral nerve blocks.

PMID- 14727289
TI  - Has the silver bullet been found?

PMID- 14727292
TI  - Clarifying the use of lidoderm patch to treat pain associated with postherpetic
      neuralgia.

PMID- 14727293
TI  - Suprascapular nerve block: an alternative method of placing a catheter for
      continuous nerve block.

PMID- 14727299
TI  - Watermarking on 3D mesh based on spherical wavelet transform.
AB  - In this paper we propose a robust watermarking algorithm for 3D mesh. The
      algorithm is based on spherical wavelet transform. Our basic idea is to decompose
      the original mesh into a series of details at different scales by using spherical
      wavelet transform; the watermark is then embedded into the different levels of
      details. The embedding process includes: global sphere parameterization,
      spherical uniform sampling, spherical wavelet forward transform, embedding
      watermark, spherical wavelet inverse transform, and at last resampling the mesh
      watermarked to recover the topological connectivity of the original model.
      Experiments showed that our algorithm can improve the capacity of the watermark
      and the robustness of watermarking against attacks.

PMID- 14727300
TI  - Intersections of two offset parametric surfaces based on topology analysis.
AB  - Conventional methods for solving intersections between two offset parametric
      surfaces often include iteratively using computationally expensive SSI
      (surface/surface intersections) algorithm. In addition, these methods ignore the
      relations between the intersection curves of parametric surfaces with different
      offset distances. The algorithm presented in this paper, makes full use of the
      topological relations between different intersection loops and calculates
      intersection loops with the help of previously calculated intersection loops. It
      first pre-processes two parametric surfaces to obtain the characteristic points,
      called topology transition points (TTPs), which can help in the subsequent
      finding of the topologies of the intersection curves. Then these points are
      categorized into several distinct groups, and we can determine the calculation
      strategy for searching initial points by analyzing the properties of these TTPs
      on the surfaces. Hence, all intersection curves can be marched from initial
      points by the tracing algorithm. The proposed algorithm could calculate
      intersection curves robustly and effectively, and has been tested to be capable
      of overcoming the degenerate conditions such as loop and singularities leaking
      that occur frequently in conventional algorithms.

PMID- 14727302
TI  - Decentralized impulsive control for a class of uncertain interconnected systems.
AB  - A great deal of stabilization criteria has been obtained from study of
      stabilizing interconnected systems. The results obtained are usually based on
      continuous systems by state feedback. In this paper, decentralized impulsive
      control is presented to stabilize a class of uncertain interconnected systems
      based on Lyapunov theory. The system under consideration involves parameter
      uncertainties and unknown nonlinear interactions among subsystems. Some new
      criteria of stabilization under impulsive control are established. Two numerical
      examples are offered to prove the effectiveness and practicality of the proposed
      method.

PMID- 14727301
TI  - A new photonic bandgap cover for a patch antenna with a photonic bandgap
      substrate.
AB  - A new photonic bandgap (PBG) cover for a patch antenna with a photonic bandgap
      substrate is introduced. The plane wave expansion method and the FDTD method were
      used to calculate such an antenna system. Numerical results for the input return
      loss, radiation pattern, surface wave, and the directivity of the antennas are
      presented. A comparison between the conventional patch antenna and the new PBG
      antenna is given. It is shown that the new PBG cover is very efficient for
      improving the radiation directivity. The physical reasons for the improvement are
      also given.

PMID- 14727303
TI  - Study on the comprehensive combustion kinetics of MSW.
AB  - The combustion behavior of typical components of MSW was examined with a thermal
      gravimetric analyzer (TGA). The experiments were done over the temperature range
      of room temperature to 1000 degrees C at a heating rate of 10 degrees C/min and
      in an oxidizing atmosphere. The results indicated that the entire weight loss
      process of each typical component of MSW consists of one to three distinct
      combustion stages. The combustion of typical components of MSW could be modeled
      by one to three independent reactions. The corresponding parameters of typical
      components of MSW such as activation energy, pre-exponential factor, and reaction
      order were determined. The calculated results using the comprehensive kinetic
      model composed of one to three independent and consecutive reactions, agreed well
      with experimental results.

PMID- 14727304
TI  - Investigation on wind energy-compressed air power system.
AB  - Wind energy is a pollution free and renewable resource widely distributed over
      China. Aimed at protecting the environment and enlarging application of wind
      energy, a new approach to application of wind energy by using compressed air
      power to some extent instead of electricity put forward. This includes:
      explaining the working principles and characteristics of the wind energy
      compressed air power system; discussing the compatibility of wind energy and
      compressor capacity; presenting the theoretical model and computational
      simulation of the system. The obtained compressor capacity vs wind power
      relationship in certain wind velocity range can be helpful in the designing of
      the wind power-compressed air system. Results of investigations on the
      application of high-pressure compressed air for pressure reduction led to
      conclusion that pressure reduction with expander is better than the throttle
      regulator in energy saving.

PMID- 14727305
TI  - Hybrid event based control architecture for tele-robotic systems controlled
      through Internet.
AB  - A new hybrid event based control architecture for tele-robotic systems controlled
      through the Internet is proposed in this paper. Different from the traditional
      event based control method, the new framework does not require every part of the
      system to be strictly event synchronized. Instead, it allows time referenced
      control components to be integrated into this framework, which makes it more
      convenient to develop Internet based control systems. Since there are two
      reference variables, time and event, in this architecture, how to coordinate
      these components with different references to keep the stability of the whole
      system is discussed in detail in this paper. To verify this new idea, an
      experiment was conducted to control the end effector of a PUMA robot tracking a
      continuous state trajectory given on-line by the remote operator. Experimental
      results confirmed the stability of such systems being controlled through the
      Internet in real-time.

PMID- 14727306
TI  - Geotechnical research on Jiangnan Tu-Dun tomb historical remains in China.
AB  - Geotechnical research on historical remains can provide new data and distinctive
      viewpoint for research on soil mechanics. Two Jiangnan Tu-Dun tombs historical
      remains were investigated by means of in situ and laboratory geotechnical tests.
      In the present paper the geotechnical properties of these man-made earthworks,
      especially ageing effect on consolidation and direct shear, and compaction
      properties of earth fill are discussed.

PMID- 14727307
TI  - Dynamic properties of composite cemented clay.
AB  - In this work, the dynamic properties of composite cemented clay under a wide
      range of strains were studied considering the effect of different mixing ratio
      and the change of confining pressures through dynamic triaxial test. A simple and
      practical method to estimate the dynamic elastic modulus and damping ratio is
      proposed in this paper and a related empirical normalized formula is also
      presented. The results provide useful guidelines for preliminary estimation of
      cement requirements to improve the dynamic properties of clays.

PMID- 14727308
TI  - Semi-active control of a cable-stayed bridge under multiple-support excitations.
AB  - This paper presents a semi-active strategy for seismic protection of a benchmark
      cable-stayed bridge with consideration of multiple-support excitations. In this
      control strategy, Magnetorheological (MR) dampers are proposed as control
      devices, a LQG-clipped-optimal control algorithm is employed. An active control
      strategy, shown in previous researches to perform well at controlling the
      benchmark bridge when uniform earthquake motion was assumed, is also used in this
      study to control this benchmark bridge with consideration of multiple-support
      excitations. The performance of active control system is compared to that of the
      presented semi-active control strategy. Because the MR fluid damper is a
      controllable energy- dissipation device that cannot add mechanical energy to the
      structural system, the proposed control strategy is fail-safe in that bounded
      input, bounded-output stability of the controlled structure is guaranteed. The
      numerical results demonstrated that the performance of the presented control
      design is nearly the same as that of the active control system; and that the MR
      dampers can effectively be used to control seismically excited cable-stayed
      bridges with multiple-support excitations.

PMID- 14727309
TI  - Investigation of newly developed added damping and stiffness device with low
      yield strength steel.
AB  - Energy dissipators, isolated-resistant and specific structural forms for
      earthquake resistance are popular topics in the research to improve shock
      resistance. In this work, experimental methods were used to investigate the
      property of low yield strength steel. Carbon content in LYS material is lower
      than that in other steels; the ultimate stress is three times the yield stress.
      The ultimate elongation rate is about 62% and the ductility is 2-3 times that of
      A36 steel. In order to overcome some defects of ordinary use metallic dampers,
      the mechanical characteristic of low yield strength steel is used to develop
      added damping and stiffness for rhombic steel plate absorber. Test of the energy
      dissipation behavior for this newly developed device indicated that LYS could
      stably dissipate or absorb the input energy of earthquake. Then, the analytical
      model for the hysteretic behavior of this new device is proposed. Comparison of
      experimental data and numerical simulation results showed that this analytical
      model is suitable for simulating the hysteretic energy behavior of this new
      device.

PMID- 14727310
TI  - Extreme value distributions of mixing two sequences with the same MDA.
AB  - Suppose [(i), i>or=1] and [Y(i), i>or=1] are two independent sequences with
      distribution functions F(X)(x) and F(Y)(x), respectively. Z(i,n) is the
      combination of X(i) and Y(i) with a probability p(n) for each i with 1<or=i<or=n.
      The extreme value distribution G(Z)(x) of this particular triangular array of the
      i.i.d. random variables Z(1,n), Z(2,n), ..., Z(n,n) is discussed. We found a new
      form of the extreme value distributions i) Phi(alpha(1))(A)(x)Phi(alpha(2))(x)
      and ii) Psi(alpha(1))(A)(x)Psi(alpha(2))(x) (alpha(1)<alpha(2)), which are not
      max-stable. It occurs if F(X) and F(Y) belong to the same MDA(Phi) or MDA(Psi).

PMID- 14727311
TI  - PH-spline approximation for Bezier curve and rendering offset.
AB  - In this paper, a G(1), C(1), C(2) PH-spline is employed as an approximation for a
      given Bezier curve within error bound and further renders offset which can be
      regarded as an approximate offset to the Bezier curve. The errors between PH
      spline and the Bezier curve, the offset to PH-spline and the offset to the given
      Bezier curve are also estimated. A new algorithm for constructing offset to the
      Bezier curve is proposed.

PMID- 14727312
TI  - Random quadralinear forms and schur product on tensors.
AB  - In this work, we made progress on the problem that [ symbol: see text] is a
      Banach algebra under schur product. Our results extend Tonge's results. We also
      obtained estimates for the norm of the random quadralinear form A:l(r)(M) x
      l(p)(N) x l(q)(K) x l(s)(H)-->C, defined by: A(e(i), e(j), e(k), e(s))=a(ijks),
      where the (a(ijks))'s are uniformly bounded, independent, mean zero random
      variables. We proved that under some conditions [ symbol: see text] is not a
      Banach algebra under schur product.

PMID- 14727313
TI  - Existence of solutions and positive solutions to a fourth-order two-point BVP
      with second derivative.
AB  - Several existence theorems were established for a nonlinear fourth-order two
      point boundary value problem with second derivative by using Leray-Schauder fixed
      point theorem, equivalent norm and technique on system of integral equations. The
      main conditions of our results are local. In other words, the existence of the
      solution can be determined by considering the "height" of the nonlinear term on a
      bounded set. This class of problems usually describes the equilibrium state of an
      elastic beam which is simply supported at both ends.

PMID- 14727314
TI  - A novel model for extending international co-operation in science and education.
AB  - In September 1994 the University of Twente, the Netherlands, and Zhejiang
      University, China, decided to cooperate in the field of science, education and
      management. After several visits of delegations from both sides it was considered
      worthwhile to explore further opportunities for mutual cooperation. The directors
      of international cooperation on each side jointly commissioned a project to
      investigate the potential in a systematic way and to establish further contacts
      where appropriate. This paper reports on the results of the research cum matching
      project. To reveal promising matches between multiple departments of both
      academic institutions a matching model for universities was designed. The study
      was carried out along two parallel lines. In the research line the theoretical
      framework was developed into a model for international university co-operation.
      Moreover, an analysis was carried out on internal, external and cultural aspects
      resulting in a set of thirty four influencing factors. In the matching line a
      total of seventy interviews were held in order to identify promising matches
      between units at both universities. This line resulted in eleven promising
      matches for further co-operation. The novel model appeared useful in analyzing
      the variety of factors and in developing matches between both universities. In
      the further implementation of the model the issues of "level of co-operation" and
      "top-down versus bottom-up" need to be addressed in more detail.

PMID- 14727315
TI  - Full time adult credential students' instructional preferences at California
      State University, Long Beach: pedagogy orandragogy?
AB  - This study investigated the instructional preferences of full time adult
      credential students after they took a live course called Principles of Adult
      Education at California State University, Long Beach (CSULB) in the fall semester
      of 2002. These full time adult credential students had been working on their
      adult teaching credentials to meet the competencies specified by the California
      Commission on Teacher Credentialing. The course introduced students to Andragogy
      developed by Malcolm Knowles out of the andragogical model developed by Lindeman
      (1926). The study used Principles of Adult Learning Scales (PALS), advanced by
      Gary Conti in 1983 to measure instructional preferences. Data were collected from
      30 (100% of 30) full time adult credential students enrolled in a live course to
      determine their instructional preferences of helping adults learn. The results of
      the study showed in most cases these adult learning professionals taught adult
      students andragogically; in some cases they taught adult students pedagogically.

PMID- 14727316
TI  - Severe intoxication after phenytoin infusion: a preventable pharmacogenetic
      adverse reaction.

PMID- 14727322
TI  - EFIS 2003. Abstracts of the 15th European Immunology Congress. June 8-12, 2003,
      Greece.

PMID- 14727323
TI  - Special anniversary issue: 25 Years of the Western Journal of Nursing Research.

PMID- 14727325
TI  - Lights, camera, action: GHA unveils civil justice reform advocacy video.

PMID- 14727326
TI  - Leadership GHA: transforming and shaping tomorrow's health care leaders.

PMID- 14727327
TI  - Plagiarism in the net age.

PMID- 14727328
TI  - Frequency of cryptosporidium in childhood diarrhoea--importance of modified acid
      fast technique.
AB  - BACKGROUND: One of the important causes of childhood diarrhoea is
      cryptosporidium, a parasitic pathogen which is usually overlooked. This study was
      therefore designed to show the importance of modified acid fast stain in the
      diagnosis of cryptosporidium in childhood diarrhoea. METHODS: Stool samples from
      300 children with prolonged diarrhoea were examined by modified acid fast
      staining a long with wet mounts in saline and iodine. RESULTS: Out of 300 samples
      five (1.7%) were diagnosed as positive for cryptosporidium. CONCLUSION: Results
      indicate that Cryptosporidiosis exists as a cause of diarrhoeal illness in our
      society. It was also noted that modified acid fast staining of stool samples is
      an important, non-invasive and useful diagnostic technique in identification of
      cryptosporidium.

PMID- 14727330
TI  - Frequency of diabetics in asteroid hyalosis patients.
AB  - BACKGROUND: A steroid hyalosis is a benign condition characterized by small white
      or yellow-white spherical opacities throughout the vitreous. The aetiology of
      this disorder is not clearly understood. Association of asteroid hyalosis with
      diabetes mellitus has been a debatable issue in ophthalmology. This study was
      carried out to determine the relationship between asteroid hyalosis and diabetes.
      METHODS: The study was carried out in the Department of Ophthalmology, Military
      Hospital, Rawalpindi. Cases were picked up during routine eye examination that
      showed evidence of asteroid hyalosis. All patients of diabetes scheduled for
      routine follow-ups were also checked for active signs of diabetes. Fasting and
      two-hour postprandial blood glucose were checked and the frequency of diabetes
      mellitus in patients with asteroid hyalosis was determined. RESULTS: Ninety-six
      cases of asteroid hyalosis were included. The median age of presentation was
      55.68 years (range 40-71). It was bilateral in thirty-six cases. Twenty-eight
      cases were positive for diabetes. CONCLUSION: The association between asteroid
      hyalosis and diabetes appears to be significant. Patients found to be having the
      findings of asteroid hyalosis should be screened for diabetes.

PMID- 14727329
TI  - Fatness, lipids, insulin sensitivity, and life style of children from high and
      low risk families.
AB  - BACKGROUND: Children show variation in certain diabetes related risk factors
      according to the family history. Early detection of high risk groups could
      prevent or delay the onset of diabetes. Insulin level and fatness of Pakistani
      children has never been compared according to family history. This study was
      designed to observe the differences in insulin sensitivity, lipids and fatness in
      children from high and low risk families. METHODS: Two groups of 8-10 year old
      school children were assessed for the differences in insulin sensitivity, lipids,
      fatness, food and activity habits. The first group had no family history for
      diabetes (low risk group, n = 40) in any first or second degree relative. The
      second group had positive family history of diabetes (high risk group n = 40)
      Data were collected through questionnaire sent to parents and children's
      interview. Blood test and anthropometric assessments were done at the schools by
      a physician. RESULTS: The two groups of children had similar level of insulin
      sensitivity. Children having positive family history for diabetes had markedly
      higher mean values for BMI, and arm fat % as compared to the controls. Though the
      low risk group had markedly higher level of total lipids and triglycerides the
      high risk group had markedly lower HDL and significantly higher LDL (p = 0.008)
      and HDL-LDL (p = 0.009) ratio than the low risk group. There was no significant
      difference in food and activity habits of the two groups. CONCLUSION: Marked
      variations in lipid profile of children from high and low risk families are
      evident at an early age. Presence of these differences in the absence of
      differences in food and activity habits and insulin sensitivity suggests that
      variation in lipid storage and metabolism could precede the appearance of reduced
      insulin sensitivity in children from high-risk families. Measures to control
      excessive fat deposition in childhood could be an initial step towards the
      prevention of diabetes and heart disease in adult life.

PMID- 14727331
TI  - Effects of maternal smoking on placental morphology.
AB  - BACKGROUND: Maternal smoking is one of leading causes of premature labour and low
      birth weight babies. Nicotine and carbon monoxide both induce degenerative
      changes as well as premature aging of placenta. Degenerative changes induce
      increased amount of collagen in chorionic villi and increased thickness of
      subtrophoblastic basement membrane. Premature aging is indicated by increased
      number of syncytial buds and higher percentage of apoptosis in smoker's
      placentae. Premature aging and degenerative changes may reduce the functional
      component of placenta and lead to abnormal outcome of pregnancy. This study was
      designed to determine the effects of maternal smoking on placental morphology.
      METHODS: Total 40 full term placentae, 20 from normal and 20 from smoker mothers
      were studied histologically. Full thickness pieces of each placenta from standard
      area were taken for paraffin embedment. Four micron thick sections were cut on
      rotary microtome and stained with haematoxylin and Eosin, Malloryis trichrome and
      hexamine silver for syncytial buds, Apoptotic cells, chorionic villous collagen
      and Subtrophoblastic basement membrane. RESULTS: This study demonstrates that
      there is extensive aging and degenerative changes in smoker's placentae. The
      aging process is shown by increased syncytial buds per unit area and high
      percentage of apoptosis. Degenerative changes are indicated by increased amount
      of collagen in chorionic villi and increased thickness of subtrophoblastic
      basement membrane. CONCLUSION: Extensive premature aging and degenerative changes
      in smoker's placentae decrease the functional component of an organ, reducing its
      nutritive and excretory functions. This may be the cause of low birth weight
      babies in smokers. Extensive loss of trophoblasts by apoptosis and syncytial buds
      may lead to hormonal imbalance and premature labour in smokers.

PMID- 14727332
TI  - Risk factors for gall bladder cancer in Karachi.
AB  - BACKGROUND: Frequency of gallbladder cancer in Karachi has been reported to be 8%
      and that from other parts of Pakistan varies between 6-7%. This is very high as
      compared with the Western studies. With this in mind a case control study was
      designed to identity risk factors responsible for gallbladder cancer. METHODS:
      This case control study included 107 histologically proven cases of gall bladder
      cancer from Jinnah Postgraduate Medical Center, Civil Hospital and two private
      hospitals of Karachi. Age and sex matched controls were of two types. Those with
      and without cholelithiasis screened sonographically. Demographic, socio-economic
      factors, life-style, dietary habits and dietary intake were recorded on a
      proforma. The cases and controls were compared for various factors using odds
      Ratio. RESULTS: Among 107 cancer cases 27 were males and 80 females (M:F = 1:3).
      Mean age of males was 59 years (range 35-82 years) and females 53 years (range 31
      70 years). One hundred and five (98%) had associated choleliathiasis. Important
      risk factors appeared to be gallstones, high parity, young age at first delivery,
      low fiber and Vitamin A intake (p < 0.01), high fat intake (p < 0.01), prolonged
      fasting hours/habit of missing dinner (OR:6.8), using repeatedly boiled or
      improperly stored ghee or oil (OR:2.6). CONCLUSIONS: According to this case
      control study major risk factors for gall bladder cancer were gallstones, dietary
      malpractices and poorly balanced diet. Poorly stored/processed food acts as a
      promoter in the presence of gall stones and may favour cancer development.

PMID- 14727333
TI  - Determinants and pattern of postpartum psychological disorders in Hazara division
      of Pakistan.
AB  - BACKGROUND: The risk of psychological disorders in women increases during the
      postpartum period. The major forms of these disorders are post partum psychoses
      and post partal depression. This study was designed to evaluate the presentation
      and sociodemographic characteristics of postpartal psychological disorders at
      Hazara division of Pakistan. METHODS: This study was carried out over a period of
      three years at three major cities of Hazara, Pakistan. One psychiatry clinic in
      each of these cities was selected and record of all the psychiatric patients was
      kept. All the patients presenting with post partal disorders were included in the
      study. A proforma was used to collect information about a wide variety of
      sociodemographic variables and presentation of disease. Frequencies were
      calculated for different variables. RESULTS: 8.66% (1248) out of 14,400 patients
      of psychiatric disorders presented with post partal disorders. 60% out of these
      1248 had post partal psychoses while the rest had post partal depression. The
      majority of our patients with post partal depression were young (20-31 years),
      illiterate (80%), having past history of psychoses/depression (70%), house wives
      (95%), from rural areas (65%), highly religious (60%), poor (90%), with husband
      away for job etc. (70%), primipara (80%) and with a live baby born (70%). A
      number of stressors were identified in 65% of subjects. CONCLUSIONS: There is a
      predictable set of risk factors for post partal psychological disorders in the
      population of Hazara. Proper identification of these risk factors during
      antenatal period with collaboration of obstetrician and psychiatrist can reduce
      the morbidity associated with this group of disorders.

PMID- 14727334
TI  - Effect of menopause on serum HDL-cholesterol level.
AB  - BACKGROUND: There is a marked difference in the risk of coronary heart disease
      between men and women of reproductive age but this gap closes with advancing age.
      It seems likely that some factors of reproductive physiology are responsible for
      this. The present study was designed to evaluate the difference in HDL
      Cholesterol level in premenopausal and postmenopausal women in relation with
      change of estradiol level. METHODS: Fifty premenopausal and 50 postmenopausal
      women were included in the study. Estradiol was estimated by radioimmuoassay
      while HDL-C was estimated by Kit method. RESULTS: There was a significant (p <
      0.01) decrease in the HDL-C level of the postmenopausal women (46.72 +/- 1.009)
      as compared with premenopausal women (63.68 +/- 1.78). CONCLUSION: HDL-C is an
      independent risk factor for coronary heart disease. This study favours the view
      that decrease in estradiol level and associated decrease in HDL-C seen in
      postmenopausal women may be responsible for the increased risk of coronary heart
      disease after menopause.

PMID- 14727335
TI  - Management of comminuted fractures of the olecranon by tension band wiring.
AB  - BACKGROUND: Open reduction and rigid internal fixation has become the generally
      accepted method of treatment for displaced fractures of the olecranon in order to
      allow early mobilisation and to prevent contracture of the elbow. Comminuted
      fractures of olecranon are unstable, therefore, bone graft and tension band
      wiring are supposed to give good stability. Here we give an account of our
      experience with this procedure. METHODS: We treated ten patients with comminuted
      fractures of the olecranon by multiple tension-band wiring and a graft from the
      iliac crest between 1999 and 2002 at Ayub Teaching Hospital, Abbottabad. After
      initial immobilization strengthening and endurance exercises were started. The
      patients were followed up for stability, muscle strength, active range of flexion
      and extension at elbow and rotation of forearm. RESULTS: The time to union of the
      fractures was 3 to 7 months. No patient reported difficulties with activities of
      daily living or symptoms of instability of the elbow. The median flexion was up
      to 135 degrees (125 degrees to 145 degrees) with a median flexion contracture of
      15 degrees (range 10 degrees to 30 degrees). The median pronation was 70 degrees
      (60 degrees to 80 degrees) and median supination 79 degrees (70 degrees to 90
      degrees). Only three patients had mild pain and loss of strength. Five patients
      had excellent and 5 good results with a median Broberg and Morrey index score of
      94.5 points (84 to 100). CONCLUSION: Our results are in accordance with those
      reported from other centres and the technique is thought to be a practical
      alternative to plate fixation of olecranon fractures with extreme comminution.

PMID- 14727336
TI  - Presentations of Meckel's diverticulum at Khyber Teaching Hospital Peshawar.
AB  - BACKGROUND: This study was conducted with an objective to observe various
      presentations of Meckel's Diverticulum in our setting and compare it with other
      national and international studies. METHODS: It was a retrospective analysis of
      hospital record carried out at the department of paediatric surgery Khyber
      Teaching Hospital, Peshawar. A total of 63 patients meeting the inclusion
      criteria were included in the study who had presented to our unit with signs and
      symptoms of Meckel's Diverticulum and who were diagnosed either by investigations
      or at surgery. All the patients were explored and resection and anastomosis
      performed. We did not do H. Pylori culture. Patients with bleeding per rectum
      were investigated by Meckel's scan. Analysis of the results was done by SPSS
      version 10. RESULTS: Majority of our patients presented with obstruction (82.5%)
      in contrast to the Western studies (around 40%) while only 4.7% presented with
      bleeding per rectum again in contrast to the Western countries (38.56%).
      CONCLUSION: There appears to be a geographical and/or racial difference in the
      presentation of Meckel's diverticulum.

PMID- 14727337
TI  - Utilization of services of homeopathic practitioners among patients in Karachi,
      Pakistan.
AB  - BACKGROUND: The practice of homeopathy is becoming very popular. There is a need
      to study and understand as to why this is happening and to raise debate on the
      issue. METHODS: The study was conducted on patients, visiting the Family Practice
      Centre, The Aga Khan University, Karachi. A questionnaire was used to collect
      information on the demographic profile, and the utilization of the services of
      homeopathic practitioners. The ethical requirements for conducting the study were
      met. RESULTS: Three hundred and eighty-seven patients were surveyed. The study
      population included more women then men, with average age of 32.6 years. The
      majority was married, well educated, in private and government service, students
      or housewives. A substantial 36.4% of the respondents had used the services of
      Homeopathic practitioners for various ailments. The five main ailments for
      consulting them were skin diseases, influenza, headache, gastro-intestinal and
      musculo-skeletal problems. The main reason for consulting Homeopathic
      practitioners was the 'recommendation of others'. The reasons for not consulting
      them were the 'lack of belief in them', 'allopaths were considered more
      effective', 'Homeopathic practitioners were considered unscientific', and 'were
      not considered a treatment option'. Among those who had consulted Homeopathic
      practitioners in the past, a substantial 67% of them were willing to consult them
      again in future. CONCLUSION: We have found a substantial utilization of services
      of Homeopathic practitioners among patients seeking allopathic treatment. Further
      studies are strongly recommended to study the need, utilization and organization
      of services offered by Homeopathic practitioners and the reasons for their
      popularity.

PMID- 14727338
TI  - Indications of caesarean section in a district head quarter hospital for women.
AB  - BACKGROUND: Rates and indications of Caesarean Section (CS) are the subject of
      controversies. The safety of elective Caesarean Section in the developed world
      has given rise to another controversy. Now the women in the developed world are
      requesting elective caesarean section by choice as a mode of delivery in the
      absence of any specific indication. The indications of CS performed in a district
      hospital were studied. METHODS: The study is descriptive in type. It was carried
      out in District Headquarter Hospital for Women, D.I. Khan in 2002. The data was
      collected from the history sheets and labour room registers. RESULTS: During one
      year period, 209 CS were performed. The rate of CS was 11.86%. Emergency CS were
      82.38%, elective CS were 17.14%, 18.1% were booked and 81.9% were un-booked.
      Antepartum haemorrhage contributed to 23.92%, obstructed labour to 18.09%,
      failure of progress to 13.3%, previous CS to 11.9% and cephalopelvic
      disproportion to 11.9% of the indications. Miscellaneous conditions contributed
      to 7.14% of the cases. In the majority of cases more then one factors had
      operated. CONCLUSION: The study showed that all CS performed had specific
      indications. Caesarean Section was accepted as the last resort for delivery.

PMID- 14727339
TI  - Evaluation and management of diabetic foot according to Wagner's classification.
      A study of 100 cases.
AB  - BACKGROUND: Wagner's classification is the most widely utilized grading system
      for lesions of the diabetic foot. The aim of the study was to evaluate and manage
      the different lesions of diabetic foot according to Wagner classification. This
      will help to describe the lesions we treat study and compare outcomes and also
      identify measures to decrease morbidity and mortality due to diabetic foot
      disease. METHODS: The study was conducted in surgical "c" unit of Khyber Teaching
      Hospital, Peshawar from July 2002 to June 2003. 100 patients with diabetic foot
      disease were included in the study. Detailed history, clinical findings and
      investigations were recorded. Lesions were graded according to wagner
      classification and appropriate medical and surgical treatment carried out.
      RESULTS: Diabetic foot disease formed 1.04% of total admissions and 0.23% of OPD
      patients. 62 (62%) were males and 38 were females. Common age group was 40-60
      years, 6 patients had grade 0, 14 grade 1, 25 with grade 2, 30 with grade 4 and 4
      with grade 5 lesions. 17 patients were managed conservatively with antibiotics
      alone, 33 had incision drainage and debridement while 48 needed amputation of
      different types. Staphylococcus aureus was the commonest organism isolated.
      CONCLUSION: Majority of the diabetic foot lesions were in grade 2 to 5. Lesser
      grade lesions responded well to conservative treatment with antibiotics and
      surgical debridement while those with higher grades needed amputations. Effective
      glycemic control, timely hospital admissions, approximate surgical/medical
      treatment along with patient education in foot care can decrease morbidity and
      mortality due to diabetic foot disease.

PMID- 14727340
TI  - A comparison of sealing capabilities of amalgum, GIC and zinc oxide eugenol
      cement when used as retro grade filling materials (in vitro study).
AB  - BACKGROUND: The objective of this study was to compare sealing capabilities of
      different filling materials when used as retrograde filling materials following
      apiceotomy (to check their sealing abilities as retro filling). In this study
      apical seal obtained following reverse retrograde root filling with amalgam, was
      compared with those obtained with, Glassinomer (GIC) and Zinc oxide eugonal
      (ZnO2E) cement. METHODS: The root canals of 50 extracted single rooted upper
      anterior human teeth were used in this study. The root canals were instrumented
      and obturated with laterally condensed, gutta-percha and zinc oxide sealer. Each
      tooth was a pically resected at 90 degrees to its long axis and the root surface
      isolated with two coats of nail polish. Teeth were divided into 4 groups, the 1st
      group received amalgam retrograde filling, the 2nd and 3rd group was retro filled
      with GIC and ZnO2E cement respectively and the 4th control group received no
      retrograde root filling. All these teeth were suspended in 1% methylene blue dye
      at room temperature for 72 hours, the roots were sectioned and dye penetration
      measured by using (stereomicroscope) microscope. The sealing abilities of these
      materials were determined by their ability to inhibit dye penetration. RESULTS:
      The result of this study has shown that GIC is just as effective as amalgam but
      ZnO2E cement showed poor sealing abilities. CONCLUSION: GIC is just as effective
      as Amalgam as a retro-sealer and on some instance, better then it, but a long
      term in vivo study is required to prove it.

PMID- 14727341
TI  - Detecting the apical constriction in curved mandibular molar roots--preflared
      versus nonflared canals.
AB  - BACKGROUND: Achieving and maintaining correct working length is critical to
      success in endodontic therapy. This involves placing the file in to the canal to
      feel the apical constriction, preparing the canal upto that extent and then
      filling the entire canal upto the apical constriction with gutta percha points.
      Detection of the apical constriction is affected if the coronal part of the canal
      is narrow or obstructed due to dentine deposition. This usually happens in curved
      canals and gives the operator a false feeling of the apical constriction. The aim
      of this study was to compare the effect on tactile detection of apical
      constriction in mandibular molars with curved roots, between the preflared and
      non-flared root canals. METHODS: This study was carried out at Armed Forces
      Institute of Dentistry, Rawalpindi, Pakistan, from February to April 2002.
      Seventy patients coming for the endodontic treatment of their mandibular first
      molars were selected. The study included only mandibular molars with curved
      mesial canals. The total no of patients were divided equally into the preflared
      and non-flared groups. In both groups a No. 15 K file was used to detect or feel
      the apical constriction but in the preflared group the coronal portion of the
      canal was flared/prepared using Hedstrom files (No. 25-55) and Gates Glidden
      Drills No. 02 to No. 05 before inserting the No. 15 file. The tooth was
      radiographed at this moment and the distance between the tip of the file and the
      radiographic apex was measured. The location of the tip was classified as: a)
      Within 1 mm of the radiographic apex, b) Under extended, more than 1 mm of
      radiographic apex, and c) Over extended, beyond the radiographic apex. RESULTS:
      In the non-flared group 31.4% belonged to group 'a', 40% to group 'b', and 28.57%
      to group 'c'. In the flared group 80% belonged to group 'a', 5.7% to group 'b',
      and 14.28% to group 'c'. CONCLUSIONS: Results of this study suggest that
      preflaring greatly improves the tactile sense to feel the apical constriction in
      curved canals.

PMID- 14727342
TI  - Evaluation of the Ochsenbein-Luebke flap technique in periapical surgery at
      Punjab Dental Hospital Lahore Pakistan.
AB  - BACKGROUND: There have been no direct studies comparing the Trapezoidal flap with
      the Ochsenbein-Luebke flap in endodontic surgery. The present study is aimed to
      provide an insight into the relative performances of these two procedures.
      METHODS: This comparative study, carried out at Punjab Dental Hospital Lahore
      Pakistan from May to October 1998, involved 120 patients (60 in each group).
      Evaluation of technique(s) involved assessment of intra-operative technical
      considerations as well as postoperative morbidity, healing and cosmetic results.
      RESULTS: It was found that O-L flap is easy to reflect, has good visibility, less
      bleeding duration and is easy to handle during surgery. Stitches are less time
      consuming, there is less tearing, better cosmetic result and no recession of
      gingiva. However more studies should be done to evaluate the procedure in larger
      number of patients.

PMID- 14727343
TI  - Hepatitis B seropositivity among chronic liver disease patients in Hazara
      division Pakistan.
AB  - BACKGROUND: Hepatitis B virus infection is one of the major health problems in
      the developing countries including Pakistan. The present study was conducted to
      document the frequency of Hepatitis B seropositivity in patients with chronic
      liver disease in the Hazara Division. METHODS: Serum samples were collected form
      893 patients suffering from chronic liver disease (CLD) from all parts of the
      Hazara Division during period July 2000 to July 2002. Hepatitis HBsAg was
      detected by the immunochromatographic method. RESULTS: A total of 271 (30.35%)
      tested positive for HBsAg including 199 males (73.43%) and 72 females (26.56%).
      CONCLUSION: There is a high frequency of HBV seropositive individuals of both
      sexes among patients referred for chronic liver disease. These frequencies
      obtained for Hazara Division compare well with figures from other parts of
      Pakistan as well as developing countries.

PMID- 14727344
TI  - Transfusion associated graft versus host disease.
AB  - Transfusion associated graft versus host disease (TA-GVHD) results from
      engraftment of viable donor T-lymphocytes in recipient that can not recognize or
      destroy them. It is seen in immunocompromised patients and pre-mature neonates.
      It can also occur in immunocompetent individuals receiving blood from first
      degree relatives. It has emerged as single most common cause of death resulting
      from transfusion. Patients with B-cell malignancies appear to be especially at
      risk. TA-GVHD is associated with 80-90% mortality. Death most commonly occurs due
      to infection or haemorrhage secondary to pancytopenia. It is therefore important
      to prevent its occurrence. Prevention can be achieved either by complete removal
      of T-lymphocytes from donors blood or by abolishing their proliferating
      potentials. Available methods of leuko-depletion are not effective in preventing
      TA-GVHD. Only effective way is to inactivate T-lymhocytes. This can be achieved
      by irradiating blood product with gamma or X-ray irradiation. The concerns about
      malignant transformation of cells or reactivation of intracellular viruses have
      not been proved so far. Newer technologies for T-cell inactivation, which are not
      based on irradiation, are currently under trial.

PMID- 14727345
TI  - Syndromic and non-syndromic deafness, molecular aspects of Pendred syndrome and
      its reported mutations.
AB  - Deafness means partial or complete hearing impairment and is one of the most
      prevalent sensory defects in humans. It can be due to genetic or environmental
      causes or a combination of both and may be Syndromic (associated with additional
      clinical features) or nonsyndromic (no other recognizable abnormal associated
      phenotype). The overall impact of hearing impairment is greatly influenced by the
      severity of hearing defect and by the age of onset. If defect is severe and
      presents in early childhood, it has dramatic effect on speech acquisition and
      thereby cognitive and psychosocial development. The mutations shown in the paper
      results in the conformational changes of protein and influence the phenotype of
      the affected individuals. For recessive cases of deafness it is possible to
      reduce the incidence of deafness by carrier screening in the families with
      multiple affected individuals and genetic counselling. Pendred Syndrome can be
      characterized by the triad composed of familial goitre, abnormal perchlorate
      discharge and congenital deafness.

PMID- 14727346
TI  - [Tissue engineering used in andrology].
AB  - Trauma, tumor, disease and congenital abnormalities may lead to genital organ
      damage or function failure, and consequently the requirement of its
      reconstruction. Tissue engineering follows the principles of cell
      transplantation, materials science and engineering toward the development of
      biological substitutes that would restore and maintain normal function. These new
      techniques have been recently introduced into the field of andrology. Based on
      the latest advances, the present paper afferds a general prospect of the future
      direction of the development of tissue engineering in andrology.

PMID- 14727347
TI  - [Expression and significance of GFR alpha 1 gene in the recovery spermatogenesis
      of mice].
AB  - OBJECTIVE: To discuss the expression and significance of glial cell-derived
      neurotrophic factor (GDFN) receptor alpha 1 gene (GFR alpha 1) in the recovery
      spermatogenesis of mice. METHODS: Adult Kunming mice were injected
      intraperitoneally with 2 doses of busulfan (10 mg/kg) 24 days apart so as to
      establish the recovery spermatogenesis model. Testes were harvested 1 w, 2 w, 3
      w, 4 w, 6 w, 8 w and 10 w after the second injection, and normal testes were used
      as control. The recovery spermatogenesis was observed by light and electron
      microscopy, and the GFR alpha 1 mRNA was measured by semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and in situ hybridization.
      RESULTS: The expression of GFR alpha 1 mRNA increased significantly at 1 w and
      reached its peak at 2 w after the second injection [(104.72 +/- 24.4)% vs normal
      control, P < 0.01]; its expression reduced significantly at 3 w and reached its
      valley at 4 w [(20.77 +/- 4.25)% vs normal control, P < 0.01], and then increased
      gradually and restored to the normal level at 10 w. GFR alpha 1 mRNA was mainly
      expressed by undifferentiated spermatogonia. CONCLUSIONS: In the course of
      recovery spermatogenesis, the expression of GFR alpha 1 plays a key role in
      turning the spermatogonial stem cell reactivity to GDNF, which promotes self
      renewal at a high level, or results in differentiation at a low level.

PMID- 14727348
TI  - [Experimental research on spontaneous benign prostatic hyperplasia in old dogs].
AB  - OBJECTIVES: To investigate the pathoanatomize histological and biochemical
      characteristics of benign prostatic hyperplasia (BPH) by use of old dogs with
      spontaneous BPH as animal models. METHODS: Old dogs aged 6 to 13 years were
      recruited after anus check, B-ultrasonic examination by recta spy and measurement
      under surgical exploration. Ten dogs with notable prostatic hyperplasia were used
      as models, and 6 with non-hyperplasia prostate as control. Serum testosterone
      (T), estrogen (E2), ACP and prostatic specific antigen (PSA) were analyzed, and
      prostates were checked histologically. RESULTS: Prostate volume of the BPH group
      was significantly bigger than those of the control group, (14.7 +/- 2.3) and
      (13.8 +/- 1.9) cm3 vs (8.4 +/- 1.0) and (8.4 +/- 1.9) cm3, P < 0.01. Serum T
      [(14.3 +/- 2.9) vs (16.4 +/- 4.0) nmol/L] and E2 [(137.6 +/- 70.8) vs (164.4 +/-
      82.0) pmol/L] were not different between the two groups (P > 0.05). ACP of the
      BPH group was higher than that of the control group [(6.63 +/- 2.76) vs (4.92 +/-
      2.19) U/L], but the difference was not statistically significant (P > 0.05).
      There was significant difference between the BPH group and the control group in
      PSA level [(5.6 +/- 0.78) vs (3.1 +/- 0.54) microgram/L, P < 0.01]. The tissue
      slides of the BPH prostates showed hyperplasia with raised height of epithelium,
      and many long and offsetting mammillae in the gland cavity due to epithelium
      hyperplasia. CONCLUSION: Old dogs with spontaneous BPH are useful animal models
      for the etiological and pharmacological researches of human BPH.

PMID- 14727349
TI  - [A study of aspermia-related genes by genchips and analysis of the RAP1A gene].
AB  - OBJECTIVE: To study the differential gene expression profiles between the normal
      and aspermia human testes by genechips. METHODS: Probes were prepared from mRNA
      extracted from both normal and aspermia testes and employed on Biostar H-40s
      genechips to detect the differential gene expression profiles. A distinctly up
      regulated gene RAP1A was analyzed by bibliogrphic retrieval. RESULTS: Six hundred
      and twenty-three differential expressed genes were found, among which the
      distinctly up-regulated gene RAP1A was closely related to human sperm regulation.
      CONCLUSIONS: Screening the differential gene expression profiles between the
      normal and aspermia human testes by genechips can be used in the study of
      aspermia-related genes.

PMID- 14727350
TI  - [Experience of treating Peyronie's disease by plaque thinning with carbide burs
      and improved Nesbit technique].
AB  - OBJECTIVE: To investigate the efficacy of plaque thinning with carbide burs and
      improved Nesbit technique in the treatment of Peyronie's disease. METHODS: Follow
      up studies were made on 11 patients with Peyronie's disease treated by plaque
      thinning with carbide burs and the improved Nesbit technique. RESULTS:
      Satisfactory results were achieved in all the cases. Nine cases without ED could
      now complete sexual intercourse. Of the 8 cases with penile curvature, only 2
      failed to be completely corrected. And of the 5 cases with erectile pain, only 2
      still had slight intermittent pain during erection. However, neither the
      incompletely corrected curvature nor the slight intermittent pain affected the
      patients' sexual life. CONCLUSIONS: Plaque thinning with carbide burs and
      improved Nesbit technique for the treatment of Peyronie's disease have many
      advantages, such as easy manipulation, good short-term results, few
      complications, and rare recurrence, while its long-term results are not yet
      clear.

PMID- 14727351
TI  - [Treatment of long-segment urethral stricture by free internal prepuce lamina
      patch urethroplasty].
AB  - OBJECTIVE: To investigate the effect of free internal prepuce lamina patch
      urethroplasty on long-segment urethral stricture. METHODS: Eight patients of long
      segment urethral stricture underwent resection of atresia posterior urethra
      and/or incision of stricture anterior urethra, free internal prepuce lamina patch
      as of corresponding length and width were taken for the reconstruction of the
      urethra, and mean while multi-hole silica ge tract was placed in the urethra.
      RESULTS: Miction was easy and fluent in 7 cases, and unobstructed in 1 case after
      two urethral soundings. CONCLUSION: Free internal prepuce lamina patch
      urethroplasty was a good method for treating long-segment urethral stricture.

PMID- 14727352
TI  - [Protein and mRNA expression of nitric oxide synthase isoforms I and III in rat
      penile spongium tissues].
AB  - OBJECTIVE: To investigate protein and mRNA expression of nitric oxide synthase
      (NOS) isoforms I and III in rat penile tissues. METHODS: Penile tissues from male
      SD rats were investigated. The protein expression of NOS I and III in rat penis
      was confirmed by immunoprecipitation and Western blot. Gene expression of both
      NOS I and III was identified by reverse transcription-polymerase chain reaction.
      RESULTS: The mRNA and protein products of NOS I and III are both expressed in
      normal rat penile spongium tissues. But, NOS III mRNA and protein products are
      more highly expressed than those of NOS. CONCLUSIONS: These findings support the
      possibility that penile erection is regulated by different NOS isoforms in rat
      penile tissues.

PMID- 14727353
TI  - [Effect of trial transfer on embryo transfer techniques].
AB  - OBJECTIVE: To evaluate the effect of trial transfer on embryo transfer. METHODS:
      Embryo transfer guided by ultrasound was performed in 114 cycles. And trial
      transfer was accomplished in 101 of them prior to embryo transfer. The clinical
      pregnancy rate and embryo implantation rate were compared between the group with
      trial transfer and the group without, and also among the sub-groups formed
      according to the difference between the trial transfer position and the actual
      embryo depth. RESULTS: There was no statistically significant difference in the
      clinical pregnancy rate and embryo implantation rate between the group with trial
      transfer and that without trial transfer(59.41% vs 61.54%, 35.81% vs 31.43%, P >
      0.05), nor was there between the two subgroups of the group with trial transfer
      (61.54% vs 58.67%, 40.79% vs 34.09%, P > 0.05). CONCLUSION: As far as modern
      embryo transfer techniques are concerned, trial transfer can not provide accurate
      guidance for the depth of embryo transfer.

PMID- 14727354
TI  - [Seminal plasma angiotensin II detection and its clinical implication].
AB  - OBJECTIVE: To investigate the variation of seminal plasma angiotension II (Ang
      II) in infertile men and its clinical implication. METHODS: Ang II values in
      paired blood plasma and seminal plasma from 43 infertile men(13 azoospermia, 8
      asthenozoopermia, 17 asthenozoospermia and 5 cases with normal semen parameters)
      and 10 normal controls were obtained by SPE-HPLC-RIA. All semen samples with
      spermatozoa were analyzed by CASA for sperm count, motility and other parameters.
      Acrosome reaction rate (AR) was assessed by triple-stain. RESULTS: The mean
      concentration of seminal plasma Ang II was 4 times as high as that of blood
      plasma in all patients and controls (P < 0.01), but there was no correlation
      between them. The seminal plasma Ang II of azoospermic patients was higher than
      that of other infertile men and controls(P < 0.05), but no difference was found
      between the latter two groups. There was no correlation between seminal plasma
      Ang II values and other traditional parameters of sperm together with AR.
      CONCLUSIONS: Seminal plasma Ang II may be secreted locally in male reproductive
      tract. In addition to testis and epididymis, prostate and/or seminal vesicle may
      also be the source of it. The reason why seminal plasma Ang II of azoospermic
      patients is higher than that of others remains unknown. Further study is required
      to clarify the exact role of seminal plasma Ang II in the mechanisms of male
      fertility regulation.

PMID- 14727355
TI  - [Investigation on the sperm quality of 549 college students in Chengdu area].
AB  - OBJECTIVE: To evaluate the sperm quality of college students in Chengdu area.
      METHODS: A computer assisted sperm analysis (CASA) was made of the sperm
      concentration, grade A sperm, grade B sperm, sperm viability rate and movement
      parameters (VCL, VAP, VSL, LIN, STR) of 549 volunteers from 14 colleges in
      Chengdu area. The volunteers were divided into normal and abnormal groups
      according to the criteria (sperm concentration > or = 20 x 10(6)/ml, grade A and
      B sperm > or = 50% or grade A sperm > or = 25%). The results were compared with
      the data reported in China. RESULTS: Among the 549 volunteers, the sperm
      concentration was (50.90 +/- 27.31) x 10(6)/ml, grade A and B sperm was (42.21 +/
      15.38)%, grade A sperm was (29.48 +/- 13.71)%, and the sperm viability rate was
      (56.40 +/- 14.77)%. The volunteers with normal sperm accounted for 62.84%
      (345/549) in contrast with abnormal (37.16%, 204/549). Among the 204 volunteers
      with abnormal sperms, there were 187 (90.67%) with abnormal motility, 39 (19.21%)
      with abnormal concentration, 22 (10.78%) with both abnormal concentration and
      abnormal motility. There were no volunteers without sperm. Among the 345
      volunteers with normal sperm, the VCL, VAP and VSL were above 25 microns/s, and
      the VCL, VAP, VSL, LIN and STR were significantly higher than those of the
      abnormal group (P < 0.01). Moreover, the sperm concentration and the sperm
      viability rate in 549 volunteers, including 345 volunteers with normal sperm,
      were lower than the data reported in China. CONCLUSIONS: Due attention should be
      paid to the sperm quality of the college students in Chengdu area, whose sperm
      concentration and sperm viability rate have a tendency to decrease.

PMID- 14727356
TI  - [Analysis of mood factors in prostatitis and Molida therapy].
AB  - OBJECTIVES: To analyze the mood factors in prostatitis and evaluate the effects
      of Molida psychological therapy. METHODS: Two hundred and thirty-six chronic
      prostatitis patients were divided according to the course of disease into above 6
      months group (n = 31) and below 6 months group(n = 205) as well as into sexual
      disease group(n = 25) and non-sexual disease group(n = 211). An investigation was
      made by self-rating method on the basis of the National Institutes of Health
      Chronic Prostatitis Symptom Index(NIH-CPSI) and Symptom Checklist 90 (SCL-90) and
      56 cases were rated again after Molida therapy. RESULTS: 1. The scores of SCL-90
      in 236 prostatitis patients were significantly higher than normal(P < 0.01). The
      factor scores of SCL-90 showed one-item positive in 107 patients (45.2%), of whom
      27 (25.2%) had depressive disorder and 80(74.77%) had anxiety (23 with
      significant compulsion). Thirty-eight cases(16.1%) were two items positive. 2.
      The scores of SCL-90 were significantly higher in the > 6 months group of history
      and the sexual disease group than in the control group (P < 0.01). 3. The scores
      of NIH-CPSI showed a positive correlation with those of SCL-90 and both scores in
      43/56 cases were significantly decreased after psychological treatment (P <
      0.01). CONCLUSIONS: The mood factor plays an important role in aggravating
      symptoms in chronic prostatis patients and causes difficulty for management.
      Molida may significantly improve the mood and symptoms of the chronic prostatitis
      patient.

PMID- 14727357
TI  - [Effects of different dosages of cyclosporine A on the semen parameters of renal
      transplant patients].
AB  - OBJECTIVES: To evaluate the effects of different dosages of cyclosporine A (CsA)
      on the main semen parameters and sperm morphology of the patients after renal
      transplantation. METHODS: The semen of 18 patients after renal transplantation
      treated with different dosages of CsA was analyzed and the semen parameters and
      sperm morphology were compared with those of 12 normal volunteers. RESULTS: There
      was not significant difference between the main parameters of the patients
      treated with 1.5-3.0 mg.Kg-1.d-1 of CsA and 3.1-5.5 mg.Kg-1.d-1 of CsA and those
      of the volunteers (P > 0.05), but the rate of normal sperm morphology was
      significantly different between the two groups(P < 0.05). CONCLUSIONS: Different
      therapeutic dosages of CsA did not have any effect on most of the semen
      parameters of the patients after renal transplantation, but did affect the sperm
      morphology.

PMID- 14727358
TI  - [The localization and potential function of androgen receptor mRNA in rat
      submaxillary].
AB  - OBJECTIVES: To study the distribution and potential function of androgen receptor
      (AR) mRNA and AR in rat submaxillary. METHODS: In situ hybridization using
      digoxigenin-labled oligonucleotide probes, cell culture and radio-immunoassay
      were performed to localize the AR and detect the concentration of epidermal
      growth factor (EGF) in culturing supernant. RESULTS: AR mRNA hybridization
      signals were detected in glandular epithelial cells of serous acinus and
      epithelial cells in all gland ducts. The signals distributed in cytoplasma of all
      positive cells with negative nuclei; Administration of testosterone can
      significantly increase the level of EGF (P < 0.05). CONCLUSIONS: The rat
      submaxillary not only is a target organ of androgen but also can product AR by
      itself. When androgen combined with androgen receptor and can submaxillary
      function can be infected and can result in the elevation of the level of EGF
      secreted.

PMID- 14727359
TI  - [Protective effect of nitric oxide synthase inhibitor (L-NAME) on germ cell
      apoptosis in experimentally cryptorchid rats].
AB  - OBJECTIVE: To explore the protective effect of nitric oxide synthase inhibitor (L
      NAME) on the germ cell apoptosis in the rat cryptorchid. METHODS: Immature rats
      (22 day-old Sprague Dawley) were subjected to unilateral cryptorchid. Thirty rats
      were divided into three groups: sham operation group (testes still in the scrotum
      after operation); operation group; operation + L-NAME group(given L-NAME 10 mg/kg
      after operation, dip). Seven days after operation germ cell apoptosis was
      detected by terminal-deoxynucleotidyl transferase mediated-dUTP nick end
      labeling(TUNEL). Biochemical parameters (NO, NOS) were evaluated with
      spectrophotometric determination. RESULTS: At the 7th day after the operation,
      compared with the control, the number of apoptotic germ cells in the cryptorchid
      testis was increased significantly, but the testis weight was decreased
      predominantly(P < 0.01). The levels of NO and NOS in the cryptorchid were
      significantly higher than the control. CONCLUSIONS: The levels of NO and NOS
      might be involved in the germ cell apoptosis in the cryptorchid; L-NAME could
      protect the germ cell from apoptosis in experimentally cryptorchid rats by
      reducing the activity of NOS and reducing the level of NO in the testis.

PMID- 14727360
TI  - [Cloning and sequence analysis of Chlamydia trachomatis heat shock protein 10].
AB  - OBJECTIVE: To obtain Chlamydia trachomatis heat shock protein (cHSP) 10 gene from
      clinical secretion samples. METHODS: cHSP10 gene was amplified from 20 cases of
      clinical secretion samples with positive gold-labelling by specific primers of
      cHSP10 and identified by sequence analysis. RESULTS: cHSP10 full-length gene was
      amplified from 1 of 20 cases of clinical secretion samples with positive gold
      labelling. cHSP10 gene encoding 102 amino acids contains 306 bp, which nuclotide
      at position 194 changes from T to A, leading to the change of corresponding amino
      acid. CONCLUSIONS: cHSP10 gene may be cloned from clinical secretion samples with
      positive gold-labelling, which make it possible to further construct expression
      plasmid of recombinant cHSP10.

PMID- 14727361
TI  - [Distribution and resistance trends of pathogens from urinary tract infections
      and impact on management].
AB  - OBJECTIVE: To assess the bacterial profile and pattern of antibiotic resistance
      of urinary tract infections (UTIs) pathogens and to determine its clinical impact
      on management. METHODS: Midstream urine samples were submitted for culture from
      1998 to 2002, and 798 isolates were obtained for antimicrobial susceptibility
      testing including amikacin (AMK), ampicillin (AMP), cefzolin (CFZ), cefuroxime
      (CXM), ceftriaxone (CRO), ceftaxime (CTX), ceftazidime (CAZ), nalidixoc acid
      (NAL), ciprofloxacin (CIP), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin
      (NIT) for Gram-negative bacteria and oxcillin (OXA), ampicillin (AMP), cefzolin
      (CFZ), ciprofloxacin (CIP), gentamicin (Gen), vancomycin (VAN),
      trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NIT) for Gram-positive
      cocci. beta-lactamases and ESBLs were tested when needed. RESULTS:
      Enterobacteriaceae was the most frequently isolated pathogen. Among all the
      isolates, Escherichia coli accounted for 66.0%, followed by Enterococcus (6.5%),
      Klebsiella spp. (6.0%), Staphylococcus (5.4%). High resistance rates to CIP
      (56.0%), SXT (67.0%) and AMP (78.9%) were observed among the E. coli. CIP
      resistant E. coli strains are being isolated with increasing frequency. From 1998
      to 2002 the incidence of CIP-resistant increased steadily from 46.6% to 59.4%. A
      higher resistance rate to NAL was apparent. In contrast, NIT displayed a
      resistance rate of 8.9%, and AMK 4.9%. The ESBLs positive rate was 12.9% among
      the E. coli and 33.3% among the Klebsiella spp. respectively. A high resistance
      rate to CIP was also observed among the Staphylococcus (38.1%), Enterococcus
      (61.5%) and Streptococcus (85.0%), and the beta-lactamases positive rate was
      95.2% among the Staphylococcus, but a lower resistance rate to NIT among
      Staphylococcus (2.4%) and Enterococcus (11.5%). CONCLUSIONS: Resistance rates
      among common uropathogens continue to evolve and appear to be increasing to many
      commonly used agents especially to quinolones. Continued surveillance of
      resistance rates among uropathogens is needed to ensure appropriate
      recommendations for the treatment of the infections. Currently, the most
      appropriate agent for the empirical management of UTIs seems to be
      nitrofurantoin.

PMID- 14727362
TI  - [Molecular mechanism implicated in the initiation of capacitation].
AB  - The physiological changes that occur to sperm during the residence in the female
      tract are collectively referred to as "capacitation". The mechanism of action by
      which these compounds promote capacitation is poorly understood at the molecular
      level. However, some molecular events significant to the initiation of
      capacitation have been identified, such as the correlation of capacitation with
      cholesterol efflux from the sperm plasma membrane, increased membrane fluidity,
      modulations in intracellular ion concentrations, hyperpolarization of the sperm
      plasma membrane and increased protein tyrosine phosphorylation. This review
      discusses recent progress in elucidation mechanisms which regulate sperm
      capacitation.

PMID- 14727364
TI  - [The effect of calcium channel blocker on human sperm].
AB  - Calcium ion exists extensively in cells as the second messenger, and calcium
      channel blocker (CCB) is widely used to treat cardiac, skeletal muscular
      diseases. With the advances in the investigation of human sperm calcium channel,
      CCB has been proved to affect not only the shape, activation and acrosome
      reaction, but also the function of human sperm, which may afford a new approach
      to male contraception.

PMID- 14727363
TI  - [Role of sulfogalactosylglycerolipid and sulfolipidimmobilizing protein 1 in
      sperm-egg plasma membrane interaction].
AB  - Sperm-egg plasma membrane interaction is one of the important steps of mammalian
      fertilization. Many sperm and egg surface proteins are reported to be involved in
      sperm-zona pellucida interaction. Sulfogalactosylglycerolipid(SGG) is the major
      sulfoglycolipid in the germ cells of mammalian and lower vertebrates, mainly in
      the sperm head. It is a differentiation marker in spermatogenesis restricted to
      the zygotene and early pachytene spermatocytes. Sulfolipidimmobilizing protein 1
      (SLIP1) is the major sulfoglycolipid of mammalian germ cells and eggs, with the
      same localization as SGG in the sperm. SLIP1 binds specificity to SGG, both
      playing a vital role in sperm-egg interaction. This article is aimed at reviewing
      the localization of SGG and SLIP1 in the germ cell surface and their role and
      related mechanism in gamete formation.

PMID- 14727365
TI  - [Progress in researches on drugs for prostate cancer].
AB  - In the recent years, researches on drugs for prostate cancer have received more
      attention than ever before. This article reviews the mechanism and efficacy of
      such prostate cancer drugs as bicalutamide, medroxyprogesterone acetate,
      megestrol acetate, flutamide and so on, as well as the clinical data and clinical
      uses of calcitriol analogue EB1089, SR233377, etc.

PMID- 14727366
TI  - [Chinese traditional medicine yi kang ling to treat immunity infertility caused
      by anti-sperm antibody: the experimental research II].
AB  - OBJECTIVE: To observe the effects of Chinese traditional medicine Yi Kang Ling
      (YKL) on immunity infertility caused by anti-sperm antibodies (AsAb). METHODS:
      With the AsAb infertile rabbit as the experimental model, seventy-five pairs of
      New zealand rabbits were divided into three group including YKL treatment group
      (sub-divided into mini-, midi- and maxi-dosage groups), prednisone treatment
      group and non-treatment group. Rabbits of the YKL treatment sub-groups were
      further divided into M+F- (male positive, female negative), M-F+, (male negative,
      female positive) and M+F+ (male positive, female positive) pairs according to
      their initial AsAb detection results. The control group consisted of five pairs
      of normal rabbits. When the expected AsAb reversing ratio was achieved, the
      rabbits were matted and observed for the number of the pregnant and the weight of
      the newborn. RESULTS: Statistics showed that in M+F- pairs both the midi-dosage
      of YKL and prednisone treatment groups had fertility, in the mini- and maxi
      dosage of YKL treatment groups, 20% of the female rabbits failed to be pregnant,
      while in the non-treatment group, 60% female rabbits remained sterile. The
      sterile ratios of the M-F+ pairs in the mini-, midi- and maxi-dosage of YKL and
      prednisone treatment groups were 0, 20%, 25% and 25%, respectively, while the
      sterile ratio in the non-treatment M-F+ group was 40%. In M+F+ groups, the
      sterile ratios of the three YKL sub-groups, prednisone treatment and non
      treatment groups were 20%, 20% and 60% respectively. In the control group the
      sterile ratio was 20%. The weight of the newborn rabbits were around 50 grams
      with no visible malformation. CONCLUSIONS: YKL can effectively reverse the AsAb
      positive results, and restore the fertility of female rabbits. Mini-dosage of YKL
      for 45 days produced the best results and maxi-dosage of YKL had no negative
      effects on the weight of the newborn rabbit.

PMID- 14727367
TI  - [Clinical trials of antiphlogistic agent series in treating chronic nonbacterial
      prostatitis].
AB  - OBJECTIVE: To investigate the curative effect of antiphlogistic agent series on
      treating chronic nonbacterial prostatitis (CNP). METHODS: One hundred and sixty
      patients were randomized into 4 groups for an 8-week clinical observation: group
      A (oral antiphlogistic medicinal granules only), group B (oral antiphlogistic
      medicinal granules + retention enema), group C (oral antiphlogistic medicinal
      granules + rectal), and group D (antiphlogistic medicinal granules + rectally +
      hip bath). Single blind trials were employed. RESULTS: The curative rates of the
      4 groups were 37.5%, 57.5%, 52.5% and 82.5% respectively, while the total
      efficacy rates were 42.5%, 82.5%, 77.5% and 92.5% respectively. Compared with
      groups A, B and C, the curative rate of group D was significantly higher (P <
      0.05). The difference in efficacy rates was slight between groups B and D (P <
      0.05), but significant between groups A and C (P < 0.05). CONCLUSIONS: Combined
      treatment therapy can improve the effect of CNP treatment and clear away heat and
      toxic material. The antiphlogistic agent series, with the effect of motivating
      blood circulation and removing blood stasis, turned out to be an effective
      traditional Chinese medicine in treating CNP.

PMID- 14727368
TI  - [Significance of synaptic connectivity reduction for pathogenesis, clinical
      picture and course of schizophrenia].
AB  - Synaptic connectivity disorders are significant in the pathogenesis of
      schizophrenia. Myelinization and abnormal function of oligodendroglia are the
      most important factors damaging synaptic connectivity. The main phase of the
      pathogenetic process leading to schizophrenia is the loss of synaptic
      connectivity below critical level, dependent on primary synaptic density (caused
      by genetic and perinatal factors), and on elimInation of synaptic connection
      during late adolescence and early adulthood. Various clinical pictures and
      courses of schizophrenia are related to various levels of synaptic density
      reduction. New imaging techniques (MRI, MTI, DTI) found many abnormalities in
      white matter--in myelin and oligodendroglia in schizophrenics. Actually, we don't
      know, whether these abnormalities are primary (caused by genetic factors) or
      secondary (caused by other factors, fox example by glutamatergic excitotoxicity
      of oligodendroglia).

PMID- 14727369
TI  - [Lipid abnormalities in schizophrenia--current knowledge].
AB  - Preclinical and clinical data suggest that lipid abnormalities are involved in
      the pathogenesis of schizophrenia. The arguments in favour of this theory come
      from assessments of reduced tissue levels of essential fatty acids, altered
      phospholipases A2 enzyme activity and genetic studies on polymorphisms of their
      genes, increased brain levels of apolipoproteins D and L, increased turn-over of
      brain phospholipids in phosphorus-31 magnetic resonance spectroscopy, evaluation
      of the niacin flush test as a possible diagnostic marker and promising results of
      treatment trials using supplementation with eicosapentaenoic acid preparations,
      although some inconsistencies need further examination.

PMID- 14727370
TI  - [Clinical and neuropsychological correlates of proton magnetic resonance
      spectroscopy detected metabolites in brains of first-episode and schizophrenic
      patients].
AB  - OBJECTIVE: This study examined 1H MRS detected metabolite levels (in left
      frontal, temporal lobes and thalamus) and clinical and cognitive features of
      patients with first-episode and chronic schizophrenia. METHOD: We studied 31
      first-episode patients (group 1) and 17 chronic patients (group 2) with ICD-10
      diagnosis of schizophrenia (and 13 healthy subjects). Patients were also assessed
      by the means of PANSS, CGI, Calgary scales and WCST, TMT, Stroop tests. RESULTS:
      We did not observe statistically significant differences in metabolite levels
      between group 1 and 2. We observed only a trend toward higher Cho level in
      temporal lobe in group 2 and lower NAA level in group 1. When comparing with the
      control group we observed a significantly higher Cho level in the frontal lobe
      (group 1,2) (p < 0.05). We observed a trend toward lower NAA levels in the
      frontal lobe (group 1,2), and lower NAA level in the temporal lobe (group 1).
      Patients with chronic schizophrenia performed significantly worse in WCST, TMT
      and Stroop tests (p < 0.05). CONCLUSION: These results suggest, that
      abnormalities in metabolite levels in frontal and temporal lobes are present at
      the onset of disease and don't progress over time. The cognitive dysfunction is
      more prominent in chronic patients.

PMID- 14727371
TI  - [Distribution of latencies of visual evoked potentials in a sample of
      schizophrenic patients].
AB  - AIM: The aim of the study is an analysis of distribution of visual evoked
      potentials (VEP) latencies in the group of schizophrenic and healthy subjects.
      METHOD: A study was carried out on a group of 30 patients (8 males and 22
      females) with a DSM-III-R diagnosis of schizophrenia (disorganised schizophrenia-
      5, paranoid schizophrenia--12, residual schizophrenia--6, and undifferentiated
      schizophrenia--6). During the study 20 patients were given neuroleptics, 10
      patients did not receive treatment. A control consisted of 50 healthy persons (25
      males and 25 females). A stimulation of a chessboard pattern reversal (0.5 Hz,
      30', 50 cd/m2) was applied. Evoked potentials were measured between top of a head
      (Cz) and occipital leads O1 and O2. RESULTS: Schizophrenic patients have
      frequently prolonged N2 latency, and shortened P300 latency. Three groups of
      patients have been distinguished, based on a pattern of latencies: (1) patients
      with prolonged latencies of all the waves (half of the patients), (2) patients
      with prolonged N2 latency, and shortened P300 latency (one fourth of the
      patients), and (3) patients with latencies similar to control (one fourth of the
      patients).

PMID- 14727372
TI  - [Evaluation of the emotional blunting and its prognostic importance during
      neuroleptic treatment of schizophrenia].
AB  - Emotional blunting is one of the basic negative symptoms in schizophrenia. This
      symptom, historically recognised as a static symptom in this disease, is not
      surrendering of treatment. Results of some new studies suggest, that the symptom
      of emotional blunting usually changes in the course of illness and during medical
      treatment. Thus, it is of prognostic significance. AIM: The aim of study is an
      assessment of the intensity of negative symptoms in patients with schizophrenia.
      METHOD: In the study, patients of both sexes treated in the Institute of
      Psychiatry and Neurology in Warsaw were examined. Seventy patients with
      schizophrenia were examined five times: before, during and after 8-week
      pharmacological treatment. The clinical status of patients was assessed by means
      of RSEB (which estimates presence and severity of emotional blunting); PANSS
      (which estimates all psychopathological symptoms); and CGI (general clinical
      condition of patients). RESULTS: The statistical analysis showed a high level of
      emotional blunting in the investigated group. Also, there is a statistical
      significant correlation between the emotional blunting and the general patients'
      condition; decrease of emotional blunting during pharmacological treatment
      improves the results of CGI. Severity of emotional blunting before treatment is a
      predictive factor of its severity after treatment. There were no significant
      associations between the emotional blunting and other analysed factors: age,
      gender, number of hospitalizations, duration of illness, dose of drugs, global
      result of PANSS and severity of depressive symptoms.

PMID- 14727373
TI  - [Semantic satiation and language disorders in schizophrenia].
AB  - The term semantic satiation refers to the subjective experience of loss of
      meaning of a word as a result of prolonged repetition of that word. Satiation is
      a general property of neural activity: it reflects a spreading of activation in
      semantic networks and some type of inhibitory process. The aim of this paper is
      to present the hypothesis about the influence of the semantic satiation upon the
      language disorders in schizophrenia. This article contains a review of semantic
      satiation experiments in healthy participants, it also deals with the semantic
      priming paradigm, which was usually used to investigate this effect. The author
      presents a theoretical hypothesis about the connection between semantic satiation
      and language disorders. This hypothesis is based on a review of semantic priming
      experiments in schizophrenia, which provides the evidence that for schizophrenic
      patients the priming effect is larger than for healthy individuals. This
      hyperpriming effect suggests that schizophrenic patients are more susceptible to
      semantic satiation than healthy individuals, which may be a likely cause of a few
      of schizophrenia--related language disorders. Satiation may prove to be a useful
      tool for exploring the thought and language disorders in schizophrenia. Some
      empirical investigations should be made to verify the hypothesis which is
      described in this paper.

PMID- 14727374
TI  - [Quality of life of schizophrenic patients and their caregivers--comparison].
AB  - AIM: The aim of the research was to analyse the subjective quality of life of
      schizophrenic patients and their caretakers. METHOD: The quality of life was
      measured by the Polish adaptation of Mercier and Tempier's scale. We examined 50
      patients and their relatives. RESULTS: The patients' quality of life was compared
      to the quality of life of their relatives. They evaluate the quality of life
      similarly. The differences between the patients and their caretakers concern the
      evaluations of social relations. Only several demographic characteristics
      influenced quality of life. CONCLUSIONS: The similarity of quality of life is
      based on taking similar criterions of evaluation. The satisfaction from life was
      decreased for patients and their carers. It can be connected with the impact of
      schizophrenia on the family.

PMID- 14727375
TI  - [Characteristics of psychiatric day hospitals in Poland--results of a
      questionnaire survey].
AB  - AIM: The survey was aimed at describing the characteristics and therapeutic means
      offered and the organizational structure of Polish day hospitals for adults as
      well the as characteristics of patients treated there. It was part of a wider
      international project carried out within a 5 EC Framework Program and focused on
      evaluation of costs and effectiveness of day hospital treatment when set against
      conventional stationary treatment in different European health care systems.
      METHOD: Data concerning the year 2000 were gathered using a self-designed
      questionnaire sent to respondents by post. The response ratio reached 65.2%.
      RESULTS: Based on the cluster analysis, three main types of day hospitals were
      recognized: 1. day hospitals focused on rehabilitation of chronic mental
      disturbances, improvement of social functioning and support, 2. day hospitals
      being alternative to stationary inpatient treatment, 3. day hospitals intended to
      continue out-patient treatment and psychotherapy. The number of treatment places,
      working hours and work-days in a week in polled institutions was constant. Most
      frequent reasons for not admitting a patient to a day hospital were: intensive
      suicidal tendencies and acute psychotic decompensation. The most numerous
      diagnostic groups of patients treated there were schizophrenia (32.2%) and
      affective disorder (17.4%). Only 18.6% of day hospitals employed a qualified
      psychotherapist, and 32.6% had a social worker. On the average, one treatment
      place was offered to 5 patients during a year. CONCLUSIONS: The profile of
      patients admitted to Polish day hospitals for adults is not arbitrarily defined
      with respect to diagnosis and severity of disorder. However, it is possible to
      distinguish day hospitals, which have their preferences: more to rehabilitate or
      more to treat patients. In the last 16 years there was a threefold increase of
      the number of patients treated in day hospitals due to affective disturbances.

PMID- 14727376
TI  - [Pathways to psychiatric care. I. Zabkowice epidemiological catchment area].
AB  - AIM: The aim of this study was to characterise pathways to psychiatric care in
      the Zabkowice epidemiological catchment area. METHOD: In the period of two months
      between 1st February 2001 and 31st March 2001 all patients age 15 and over who
      applied to the Psychiatric Service in the Zabkowice catchment area, were assessed
      by psychiatrists for their eligibility to enter the study. Those who had
      fulfilled the entry criteria were interviewed using a Polish version of WHO's
      encounter form (EF) by the mental health professionals during their initial
      interview. RESULTS: A total of 123 patients were seen. 43% of the patients in our
      sample contacted their general practitioner first compared with 20% of those who
      first saw hospital doctors & medical specialists and 24% who came direct.
      CONCLUSIONS: The study reveals that the median interval while receiving care was
      14 weeks which is much longer than in all the European centres in previous
      studies (< 5 weeks). We didn't find any coincidence between the total interval
      since the onset of symptoms to arrival at the Psychiatric Service and the
      duration of the patients' journey.

PMID- 14727377
TI  - [Pathways to psychiatric care. II. "Psie Pole" epidemiological catchment area].
AB  - AIM: The aim of this research was to draw a pathway diagram for people with
      mental disorders in Psie Pole epidemiological catchment area, which significantly
      differs from Zabkowice epidemiological catchment area because of urbanisation and
      social status of citizens. Then to compare data characterising both pathways
      diagrams. METHOD: In the period of two months between 1st February 2001 and 31st
      March 2001 all patients age 15 and over who applied to the Psychiatric Service in
      the "Psie Pole" epidemiological catchment area, were assessed by psychiatrists
      for their eligibility to enter the study. Those who had fulfilled the entry
      criteria were interviewed using a Polish version of WHO's encounter form (EF) by
      the mental health professionals during their initial interview. Data from both
      catchment areas were compared. RESULTS: In the "Psie Pole" and "Zabkowice"
      catchments areas the main pattern of pathways to psychiatric care was similar.
      There were significant differences in the symptoms presented, diagnoses and
      intervals between both epidemiological catchment areas. CONCLUSIONS: The
      urban/semi urban and social status differences didn't influence the pathways to
      psychiatric care in "Psie Pole" and "Zabkowice" catchment areas.

PMID- 14727378
TI  - [Telepsychiatry--psychiatric advice on the Internet].
AB  - Telepsychiatry is a medical service with a use of contemporary communication
      technologies. Internet and electronic mail are included. AIM: The aim of the
      study was to examine the use of electronic mail in psychiatric advices. METHOD:
      Anonymous electronic mail (327) sent to the author from June 2001 to May 2002
      were selected. They were then processed according to the following criteria:
      patient age and gender, person who was a subject of consultation, reason and
      subject of a consultation and prevailing symptoms of a disease. Data frequencies
      were obtained. RESULTS: 75% of patients referred their own psychiatric problem.
      The most frequent reasons of consultation were: a cry for help (44%), question
      about a disease (27%), consultation of a diagnosis (16%) or a therapy (13%). The
      biggest groups of symptoms related to fear (38%), disturbances of mood (18%),
      schizophrenic symptoms (13.5%) and sexual dysfunctions (10.5%). CONCLUSIONS:
      Psychiatrists on the Internet may expect an increase of electronic mail
      applicability in psychiatric advising. There is a need of medical, legal and
      ethical regulations of by-Internet doctor-patient relationship. Electronic mail
      may be treated as a source of knowledge on psychopathological symptoms and
      epidemiology of mental disturbances amongst the internet users.

PMID- 14727379
TI  - [Experimental studies in Polish psychiatric journals].
AB  - AIM: Scientific studies in psychiatry from a methodological point of view could
      be divided into correlational and experimental. Experimental studies are based on
      active selection of independent and dependent variables, attributing values of
      the independent variable to persons under study and measuring values of dependent
      variables. An example of the experimental study is a comparison of two
      therapeutic methods. Experiments are feeble to selection, informational and
      confounding bias. METHOD: This review comprises experimental papers published in
      journals: "Psychiatria Polska", "Postepy Psychiatrii i Neurologii",
      "Farmakoterapia w Psychiatrii i Neurologii", "Rocznik Psychogeriatryczny",
      "Wiadomosci Psychiatryczne" oraz "Alkoholizm i Narkomania" from January 1998 to
      December 2002. RESULTS: 11 experimental publications, 6 randomised, 2 probably
      randomised and 3 case-control studies were found. The smallest study included 14
      persons, the largest 180 persons. The number of experimental groups varied from 2
      to 4. 9 studies evaluated features of specific methods of therapy and
      rehabilitation, among them 6 evaluated efficacy of medications. 2 studies
      evaluated relations between psychopathological and physiological variables.
      Experiments were based on groups of patients with a diagnosis of schizophrenia
      (3), alcohol and drug dependence (2), depression (3), insomnia (1), bronchial
      asthma (1), and hypertension (1). CONCLUSION: The review showed that experimental
      studies do not form a main-stream in Polish psychiatric journals.

PMID- 14727380
TI  - [Yellow fever in Venezuela].
AB  - In Venezuela the yellow fever has been presented in three wild focuses: San
      Camilo in the Tachira State, South of the Lake in the Zulia and Guayana. The last
      human case registered of urban yellow fever happened in 1918 in the city of Coro,
      Falcon State. Nevertheless, according to the epidemic registration of the
      Ministry of Health and Social Development corresponding to the epidemiological
      week no. 38 of the year 2003, 318 cases of wild yellow fever had been
      investigated (173 of the Zulia and 145 of Tachira), of which were confirmed 31,
      with a mortality of 58.0%. Previous to the appearance of this outbreak, it was
      notified an epizooty in monkeys with high mortality in November of 2002 in the
      Jesus Maria Semprum municipality of the Zulia State, persisting until September
      of 2003, extended to the Tachira State. Possible reasons of the reemergency of
      this illness are analyzed based on the high mobilization of displaced population,
      remote areas and of difficult access, high concentration of indigenous population
      (Bari, Yuepa, Wayuu) and border conflict.

PMID- 14727381
TI  - [Analysis of Bsm I polymorphism of the vitamin D receptor (VDR) gene in
      Venezuelan female patients living in the state of Zulia with osteoporosis].
AB  - Among genes implied on the osteoporosis genetics, the most studied gene worldwide
      is the receptor gene of D vitamin (VDR), through the characterization of Bsm I
      polymorphism. The main objective of this research was to analyze the Bsm I
      polymorphism of the VDR gene in a sample of 133 postmenopausal women distributed
      in three groups: 54 with osteoporosis, 24 with osteopenia and 55 normal controls
      for the disease. 28 of the women with osteoporosis presented the BB genotype,
      which is related in other countries to bone mineral density decrease, 20 had the
      Bb genotype, and 6 the bb genotype. Of the control group only 11 women presented
      the BB genotype, 36 showed the heterozygote genotype and 8 the bb genotype. The
      frequencies of the B and b alleles in the analyzed population were 0.6 and 0.4
      respectively. The BB genotype was found in 52% of the group with osteoporosis,
      and in 20% of the control group, these findings are statistically significant,
      which suggest an association between the BB genotype and osteoporosis.

PMID- 14727382
TI  - [Association of HLA class I and leukemia in mestizo patients of the state of
      Zulia, Venezuela].
AB  - The Human Leukocyte Allele (HLA) Class I (A, B, C) and Acute Lymphoid Leukemia
      and Myeloid Leukemia association, was determined by polymerase chain reaction-
      sequence specific primers (PCR-SSP) in 60 patients and 30 healthy controls. The
      results were reported as allelic frequencies and haplotype. The Chi-square
      corrected, Fisher's Test, Relative risk and etiologic fraction were calculated. A
      significant positive association was showed between HLA-B*39 (RR = 16.184; p =
      0.0237) and HLA C*03 (RR = 5.0; p = 0.0127) alleles and Mycloid Leukaemia.
      Positive associations between haplotypes 2 loci: HLA-A*02-C*03 (RR = 6.0; p =
      0.0153), A*24-C*03 (RR = 16.184; p = 0.0237), B*40-C*03 (RR = 10.706; p = 0.0021)
      and haplotype 3 loci: HLA-A*02-B*40-C*03 (RR = 8.11; p = 0.0102) and Myeloid
      Leukemia were found. No association was evident in Acute Lymphoid Leukemia. No
      negative association with Leukemias were observed.

PMID- 14727383
TI  - [Amino acid changes following intraperitoneal administration of Tityus zulianus
      scorpion venom in mice. Study with subcutaneous microdialysis and capillary
      electrophoresis].
AB  - Scorpion human envenoming is a public health hazard in the southwest of
      Venezuela. Tityus zulianus is one of the scorpion species whose venom causes lung
      edema and cardiac failure in children. These occasionally deadly manifestations
      have been attributed to a massive sympathetic discharge. The intraperitoneal
      administration of T. zulianus venom (20 micrograms/g mouse) to anesthetized mice
      during subcutaneous microdialysis caused increased secretions, dyspnea, seizures
      and death between 30 min to 2 h. Seven amino acids were analyzed by capillary
      electrophoresis with laser induced fluorescence detection (CE-LIFD) in the
      collected samples before and after the venom administration. We found an increase
      of arginine (39%), phenylalanine (40%) and glutamate (94%), with no changes in
      valine, serine and aspartate, changes were significant when the injection of
      venom and vehicle were compared and before vs after venom injection. Further
      investigation is needed to know if the observed changes could be related to the
      molecular mechanisms of the venom or some of its components and therefore with
      the envenoming symptoms. To our knowledge, this is the first report with
      subcutaneous microdialysis and CE-LIFD coupling in scorpion envenomation studies
      in vivo, in mice.

PMID- 14727384
TI  - [Study of immune response in Warao children from communities with high
      tuberculosis prevalence].
AB  - The present study was carried out in a Warao childhood population with extremely
      high tuberculosis (TB) rate of 3190/100,000 in 0-15 years old children. One
      hundred seven serum and saliva samples were tested, 32 from patients with active
      TB (27 positive and 5 negative for the tuberculin skin test, TST) and 75
      apparently healthy contact children (45 positive and 30 negative for the TST).
      The innate, immunoglobulin and cellular responses were studied. The results
      showed that both, patients and controls, had a high percentage of children with
      increased levels of complement C3 and C4 components. A high percentage of
      children with increased total serum IgA and IgG (13.8% and 79.3% respectively)
      was observed in children with TB in comparison to control children (0% and
      69.2%). A high percentage of control children had increased levels of IgM and
      sIgA (69.2% and 56.16%, respectively) in comparison to patients (48.3% and
      31.25%). Both groups showed children with increased levels of IgE. The results
      concerning to the cellular immune response to PPD and the BCG vaccination status
      showed that there was a correlation between an increase in PPD reactivity and
      age. The PPD reactivity in children less than 7 years old was similar and also
      independent of the BCG vaccination status. A significant number of children
      without or with scars (46.8% and 27.6%, respectively) showed induration values of
      0 mm to tuberculin skin test. The Candida reactivity showed a high percentage of
      children (80%) with anergy status. In conclusion, an increase in the levels of
      complement components C3 and C4 and hypergammaglobulinemia was observed in Warao
      children, and these results were independent from PPD reactivity and BCG
      vaccination. The isotype results showed that the decrease in sIgA could be and
      active disease marker, while the increase in IgM levels could represent a marker
      of recent disease.

PMID- 14727385
TI  - [Changes in cervical cytology and immune response against Chlamydia trachomatis
      in sexual workers].
AB  - There are controversies about the relationship between Chlamydia trachomatis (C.
      trachomatis) infections and development of cervical carcinoma. The objective of
      this investigation was to evaluate the relation between the presence of IgG
      against C. trachomatis in serum and IgA in cervical mucus with the prevalence of
      abnormalities in the Papanicolaou smears. One hundred sixty-six sexual workers
      were evaluated. They were checked up for sexual transmitted diseases (STD) at the
      "Unidad Sanitaria de Los Teques, Edo. Miranda". Sexual workers were interviewed
      and had a gynecological evaluation. Cervical mucus and peripheral blood samples
      were obtained to determine antibodies IgA and IgG against C. trachomatis.
      Cervical samples were taken to be evaluated by Papanicolaou staining. The
      association among the different variables was statistically evaluated (Chi
      squared and Kendal Tau). The prevalence of antibodies isotype IgA against C.
      trachomatis in cervical mucus was 45.2% and IgG in serum was 69.3%. Papanicolaou
      smear showed that 38% of women had normal or low inflammation grade, 35.5%
      moderate inflammation, 25.3% severe inflammation and 1.2% presented Low Grade
      Squamous Intraepithelial Lesion (LGSIL). There was no statistical correlation
      among presence of antibodies against C. trachomatis, presence of cervicitis and
      Papanicoloau smears. In conclusion we could not observe any relationships between
      immune response against C. trachomatis, cervicitis and Papanicolaou smears
      abnormalities. However, it is important to consider that other infections, that
      could be present simultaneously, could interfere in the interpretation of the
      results.

PMID- 14727386
TI  - [Chromosome anomalies in Venezuelan patients with multiple myeloma].
AB  - The cytogenetic study is an important prognostic factor in Multiple Myeloma (MM).
      The chromosomal analysis has demonstrated to be essential for the genetic advise
      in relation to the diagnosis, prognosis and might suggest precociously, the most
      appropriate treatment for the majority of hematological malignancies. The
      objective of this investigation was to identify the chromosomal abnormalities in
      samples of bone marrow (BM) from patients with diagnosis of MM. The chromosomal
      studies were carried out in BM cultures, following the technique described by
      Yunis. Without exception the analysis was carried out previous to any treatment
      with cytostatics. Twenty two samples of BM were received for chromosomal studies
      in the Unit of Medical Genetics of the University of the Zulia (UGM-LUZ). In 19
      out of 22 samples (86%) appropriate material was obtained by cytogenetic
      analysis; 6 (32%) showed normal karyotype and 13 (68%) presented numeric and
      structural chromosomal abnormalities. Eight (62%) of the chromosomal anomalies
      detected were numerics, three cases (38%) with hyperdiploidy involving
      chromosomes 3, 5, 7, 15, 17, 18, 19 and four cases (50%) with hypodiploidy
      involving the chromosomes 8, 16, 17, 18, X and Y. Triploidy was found in one case
      (12%). Structural abnormalities were present in 4 cases (31%) such as deletions
      5p11, 11p14, 14q32, 17p11 and 1 case (7%) presented structural and numeric
      anomalies. This study shows that the majority of patients with multiple myeloma
      have several chromosomal abnormalities with some differences from other reports.

PMID- 14727387
TI  - The role of parasites in acute appendicitis of pediatric patients.
AB  - There is little evidence regarding the relationship between parasites and acute
      appendicitis. In order to determine such a relationship, if any, 830 appendectomy
      specimens were studied. Age, sex, pathological findings and the presence and type
      of parasites and the type of parasite were analyzed. Parasites were present in 62
      cases (7.46%). Ascaris lumbricoides and Trichuris trichiura were the most
      frequently encountered parasites. These were observed, alone or in combination,
      in 45 cases (72.5%). Appendix perforation, peritonitis, necrosis and flegmonous
      appearance, were more frequent in the cases of acute appendicitis without
      parasitic infestation (p < 0.05). There were no differences between the cases
      with or without parasitic infestation (p > 0.05) In cases of peritonitis. The low
      incidence of parasites among the appendectomy specimens and the failure to
      demonstrate its relationship with all events derived of appendicitis, do not
      support the hypothesis that parasites are a major cause of appendicitis in
      pediatric patients.

PMID- 14727388
TI  - A tribute to Lloyd Kolbe.

PMID- 14727389
TI  - Elementary school secretaries' experiences and perceptions of administering
      prescription medication.
AB  - This study assessed elementary school secretaries' (n = 385) experiences and
      perceptions with student prescription medication. Sixty-nine percent (n = 246)
      reported dispensing student medication, and this group represents the focus of
      this study. One in four secretaries reported not receiving any training regarding
      administration of student medication. Of those who were trained, 28% received
      training of less than one hour, and 24% received training of one to two hours
      duration. Secretaries generally disliked the responsibility of dispensing
      medication to students, but felt prepared to do so. Most (63%) administered
      student medication five days per week. The most commonly administered categories
      included attention deficit/hyperactivity medication (92%), asthma medication
      (87%), and antibiotics (68%). Most (85%) reported they had made no medication
      errors during the past year.

PMID- 14727390
TI  - A sport-based intervention for preventing alcohol use and promoting physical
      activity among adolescents.
AB  - This study tested the potential of a novel intervention addressing alcohol
      prevention within the context of a sport program. Study participants were
      randomly assigned to one of three groups, with one group receiving the sport
      consultation (Sport), a second the sport consultation plus an alcohol
      consultation (Sport Plus), and a third a sport consultation, alcohol
      consultation, and mailed parent print materials (Sport Plus Parent). Researchers
      recruited 465 eighth graders from three schools in the northeast Florida region
      to participate in the study. The Youth Alcohol and Health Survey was used to
      collect data on alcohol and drug consumption, alcohol use risk and protective
      factors, and exercise habits at baseline and three-month post-intervention.
      Significant time effects (p's < .05) were found on three of six alcohol measures,
      both exercise measures, and four risk/protective factors, with all but one risk
      factor showing improvements over time. Time by assignment by current drinking
      status (yes/no) interaction effects (p's < .05) were found on alcohol initiation,
      length of alcohol use, quantity, heavy use, moderate physical activity, and four
      risk/protective factors, with preintervention drinking adolescents exposed to the
      Sport intervention showing the greatest improvements on all but two measures.
      Findings suggest that a brief sport-based screen and consultation tailored to
      adolescents' health habits, with and without parent materials, may potentially
      reduce alcohol use while increasing exercise frequency.

PMID- 14727391
TI  - Physicians as educators in adolescent sexuality education.

PMID- 14727392
TI  - I am a Shining Star!

PMID- 14727393
TI  - A community collaborative partnership for the Chicago Public Schools.

PMID- 14727394
TI  - Clinical information systems. End-users: four benefits: countless.
AB  - Clinical information systems aren't limited to documentation in acute care
      hospitals. Four end-users of EDIS, bar coding, oncology and patient tracking IT
      share insights on the benefits and challenges of stretching CIS to its limits.

PMID- 14727395
TI  - Surgical information systems. The technology-enhanced surgery department.
AB  - Renowned Texas cancer center uses perioperative software to boost its billing and
      revenue collection, and to make real-time patient information an enterprise
      capability.

PMID- 14727396
TI  - Enterprise resource planning: case history. Optimizing the supply chain.
AB  - A common materials management platform standardizes products, improves payment
      controls and enhances decision support for a Minnesota IDN.

PMID- 14727397
TI  - Physician practice management. Sustainable solutions for practice profitability.
AB  - Too often, IT solutions for group practices generate, at best, a quick fix.
      Forward-thinking group practice managers will evaluate technology for its
      capacity to enhance long-term profitability.

PMID- 14727398
TI  - Managed care. The health plan of tomorrow.
AB  - The increased role of consumers, along with increased healthcare costs, will
      compel health plans to use technology so everyone in the equation comes out a
      winner.

PMID- 14727399
TI  - Decision support. From opaque to crystal clear.
AB  - National health plan arms its members with sophisticated decision support tools
      to help them compare and contrast hospital performance for surgeries and
      treatment of serious medical conditions.

PMID- 14727400
TI  - Disease management. Technology-driven outcomes.
AB  - Information technology will play a significant role in identifying those
      interventions that generate best outcomes.

PMID- 14727401
TI  - What works: wireless. Cutting the cord.
AB  - Caregivers at a California community hospital improve their bedside efficiency by
      embracing switch to mobile, wireless devices.

PMID- 14727402
TI  - Widening the reach of evidence-based medicine.

PMID- 14727403
TI  - [Is Danish Christmas holiday compatible with healthy life style?].

PMID- 14727404
TI  - [Chocolate--divine food, junkfood or a narcotic?].

PMID- 14727405
TI  - [The Santa's syndrome and other risks connected to Christmas holidays].

PMID- 14727406
TI  - [Rather fat and fit than thin and boring].

PMID- 14727407
TI  - [Alcohol and waiting time to pregnancy].

PMID- 14727408
TI  - [Surgery and nutrition].

PMID- 14727409
TI  - [Nutrition, disease and agricultural politics].

PMID- 14727410
TI  - [A randomized comparison of a course in gourmet cookery versus behavior
      modification in the treatment of severe obesity].

PMID- 14727411
TI  - [Neutral and malodorous flatulence in obesity].

PMID- 14727412
TI  - [How to write a diet-book--100 percent guarantee it will become a fat notebook].

PMID- 14727414
TI  - [Criteria for Plavix (clopidogrel) administration].

PMID- 14727413
TI  - [Closer to the certain knowledge about nature--closer to Steno].

PMID- 14727415
TI  - [Late compensation for a recalled drug].

PMID- 14727416
TI  - [Objective counseling concerning drugs and drug research].

PMID- 14727417
TI  - [Prenatal diagnosis].

PMID- 14727418
TI  - [The so-called competent patient?].

PMID- 14727419
TI  - [Success and happiness Mrs/Mr chief physician].

PMID- 14727420
TI  - [Mediventure--the medical adventure of a lifetime].

PMID- 14727421
TI  - [Benefit of bilateral cochlear implantation on congenital prelingually deafened
      Chinese-speaking children].
AB  - OBJECTIVE: To evaluate the benefit of bilateral cochlear implants (BCIs) in
      prelingually deafened children on hearing rehabilitation as well as on speech and
      language development. METHOD: Two cases of congenital profound deaf children, who
      received unilateral cochlear implantation (CI, MEDEL C40+) on the age of 2 and
      7.5, respectively, were performed secondary CI in the contralateral ear on their
      age of 5 and 9.5, respectively. One year after the secondary CI, the cochlear
      implant aided hearing threshold and speech discrimination rate were tested for
      both ears separately and together. The pronounce/speech distinct rate of the BCIs
      users were evaluated by their parents, surgeon and audiologist. RESULT: In
      comparison to unilateral aided ear, the mean hearing threshold at the frequency
      250-4,000 Hz of the 2 cases with BCIs decreased by 13 dB and 11 dB, respectively.
      The speech discrimination rate of the BCIs users increased by 9% and 10%,
      respectively. The speech recognition in noise was improved. And their
      pronounce/speech distinct was improved. CONCLUSION: BCIs can provide a
      significant benefit in hearing, speech understanding, language development and
      pronounce/speech rehabilitation for prelingually deafened children.

PMID- 14727422
TI  - [Quantified research of measuring postural balance by posturography using
      inclinometer technique].
AB  - OBJECTIVE: To gain the normal values of posturography using inclinometer
      technique in people, to gain the normal values of posturography using
      inclinometer technique in people. METHOD: The messages of postural average sway
      angular velocity (omega) obtained by posturography using inclinometer technique
      in four various conditions were measured in 167 normal subjects who were grouped
      by age. RESULT: The normal omega values show that there is no correlation between
      postural balance with gender, but postural balance is related with age. The
      postural stability is at its best at the age of 20 to 60 years. The direction of
      postural sway has a large inter-individual variability, but no significant
      inclined direction is found. CONCLUSION: The results of individual tests should
      be compared with match-aged normative data in order to determine abnormal
      postural balance function. We measured many subjects and grouped by ages in
      detail. Therefore, the result can be taken as normative data of the measuring
      system. The omega value of standing on global-ottomed platform with eye closed
      could distinguish abnormal balance function of vestibo-spinal system accurately.

PMID- 14727423
TI  - [HRCT imaging characterized of congenital abnormalities of the inner ear in 45
      cases].
AB  - OBJECTIVE: To explore the high resolution CT (HRCT) image characterized of
      congenital abnormalities of the inner ear(CAIE), and its value in the diagnosis
      and treatment of CAIE. METHOD: The clinic data and axial HRCT scans of CAIE in 45
      cases were analyzed. RESULT: In 45 CAIE patients, most of them were frequently
      associated with slowly progressive sensorineural hearing loss in childhood, 15
      ears were fluctuating hearing loss. Seventeen ears were unilateral semicircular
      canal paralysis. HRCT showed that Michel type 3 cases(4 ears), Mondini type 25
      cases(39 ears). Large vestibular aqueduct malformation not associated with
      anomalies of inner ears 13 cases(23 ears), anomalies of internal auditory canal 4
      cases (5 ears). Thirteen ears were associated with outer and middle ear
      malformation. CONCLUSION: HRCT image has the important value in the diagnosis and
      treatment of CAIE, especially for the excerpt of indication of cochlear
      implantation.

PMID- 14727424
TI  - [The investigation of operative treatment of Meniere's disease].
AB  - OBJECTIVE: To investigate the clinical effect of the operations in the treatment
      of Meniere's disease. METHOD: Twenty-one patients with Meniere's disease were
      treated by the operation of decompression of the endolymphatic sac. Nine patients
      were treated by vestibular neurectomy via retrosigmoid sinus approach. The follow
      up time was between 3 and 6 years. RESULT: In 21 patients by the operation of
      decompression of the endolymphatic sac, vertigo was completely controlled in 11
      cases, substantially controlled in 4, limitedly controlled in 4 and not
      controlled in 2. In 9 patients underwent vestibular neurectomy via retrosigmoid
      sinus approach, vertigo was completely controlled. CONCLUSION: Endolymphatic sac
      surgery is the first way in the operative treatments of Meniere's disease. The
      operation of vestibular neurectomy should be adopted only in the patients who
      have failed after the operation of endolymphatic sac surgery or have lost the
      working ability substantially.

PMID- 14727425
TI  - [Distortion product otoacoustic emission test of cochlear deafness].
AB  - OBJECTIVE: To evaluate the performance of the distortion product otoacoustic
      emissions (DPOAE) test of cochlear deafness by measuring the sensitivity,
      specificity and predictive efficiency of the test. METHOD: With DPOAE examination
      data obtained from normal hearing (86 ears) and cochlear deafness (98 ears), the
      evaluation was performed by comparing the outcomes of the DPOAE level test at
      each of several frequencies (1-6 kHz) with those of the pure-tone audiogram. The
      sensitivity and specificity were combined to form receiver operating
      characteristics(ROC) curves. The area under an ROC curve was calculated to
      represent a useful overall measure of a test's performance independent of the
      particular choice of a criterion value of a test variable separating the normal
      from abnormal. RESULT: The area under an ROC curve at 1, 2, 3, 4, 6 kHz
      frequencies was 0.677, 0.777, 0.818, 0.890, 0.873, respectively. CONCLUSION: The
      DPOAE can form a useful frequency-specific objective test of cochlear deafness.

PMID- 14727426
TI  - [The application of mastoid obliteration with homograft tooth in open method
      tympanoplasty].
AB  - OBJECTIVE: To investigate the effect of open method tympanoplasty with mastoid
      obliteration with homograft tooth and reconstruction of the attic wall. METHOD:
      Fifty-two cases with cholesteatoma or skeletal ulcer otitis media were performed
      the open method tympanoplasty with mastoid obliteration with homograft tooth and
      reconstruction of the attic wall after radical mastoidectomy. RESULT: External
      auditory canals of 48 patients were normal in appearance. The transplanted
      membrane in 46 ears was survived. The dry-ears rate was 92.31% and the average
      time waited till dry-ears was 17.56 +/- 4.16 days. The air-conducting hearing
      levels of average language frequency have been enhanced over 15 dB HL in 41 ears.
      An air-bone gap of less than 20 dB HL was achieved in 31 ears. CONCLUSION: The
      open method tympanoplasty with mastoid obliteration with homograft tooth and
      reconstruction of the attic wall can recovery the anatomic structure and
      physiological function of external auditory canal and middle ear better. The long
      term effect on improving hearing was significant.

PMID- 14727427
TI  - [A longitudinal study of electrode impedance in nucleus 24M cochlear implant
      users].
AB  - OBJECTIVE: The primary goal of this study was to examine changes that may occur
      in electrode impedance over time in cochlear implant users. Secondary goal was to
      determine the timetable of mapping for patients who were cooperative quite well
      in psychophysical test. METHOD: Sixteen patients implanted with Nucleus CI24M
      participated in this study. The impedance of electrode was measured intra
      operatively, at initial stimulation, and at each mapping visits. Statistical
      analysis was conducted to assess how the changes occurring over time. RESULT:
      There was a significant increase in electrode impedance from the intra-operative
      test to initial stimulation, and a significant decrease in impedance from initial
      stimulation to the following visit. The impedance values remained stable for
      approximately 2-4 months after initial stimulation. CONCLUSION: The results
      suggest that electrode-tissue interface gradually tend to remain stable. If a
      patient cooperates quite well in psychophysics test, the psychophysical levels
      for the map should be stable after 2 to 4-month mapping.

PMID- 14727428
TI  - [Giant cell tumor of temporal bone: a report of 7 cases].
AB  - OBJECTIVE: To investigate the clinical course, auxiliary examinations, histologic
      feature, diagnosis, differential diagnosis and treatment of giant cell tumor of
      temporal bone (GCTTB). METHOD: Seven cases of GCTTB, which arose in temporal
      bone, were collected from 1990 to 2002 and analyzed clinicopathologically.
      RESULT: Seven cases with the GCTTB are reported, including 3 females, 4 males.
      The age of 7 patients between 9 to 53 years. Five tumors located in right side
      temporal bone, two in left side temporal bone. One patients was pathological I
      grade, two I-II grade, and four II grade. The clinical course were different
      according to the position of the tumors: including tinnitus 6 cases, tinnitus
      with hear loss 5 cases(2 cases with anakus of trouble side ear), vertigo 1 case,
      facial paralysis with hear loss 1 case. Radical resections were performed in five
      cases and subtotal resections in two (recurrence, one year after operation, II
      grade pathologically). Postoperative Radiotherapy was conducted in three cases.
      CONCLUSION: Diagnosis of GCTTB is based on typical histologic features and
      imagine as well as clinical information. Complete surgical resection is believed
      to be the most suitable treatment for GCTTB and postoperative radiotherapy may be
      effective.

PMID- 14727430
TI  - [Clinical analysis of 20 cases of carcinoma of the middle ear].
AB  - OBJECTIVE: In order to deeply realized the cancer of middle ear, a retrospective
      analysis of 20 cases was done. METHOD: The combined treatment (operation plus
      radiation) were adopted for all of them. The surgical procedures included sleeve
      resection for 14 cases, temporal bone resection for 3 cases, subtotal temporal
      bone resection for 3 cases. There patients with cervical metastases were treated
      by postoperative radiotherapy. RESULT: The survival rates for three years, five
      years, ten years were 50.0% (11/20), 45.0% (9/20) and 30.1% (6/20), respectively.
      CONCLUSION: Patients of cancer middle ear located mastoid process who were
      treated by sleeve resection or temporal bone resection were suitable for
      radiation therapy and clearing the cancer and reducing infection. If the can cer
      exceeded mastoid process, patients must undergo subtotal temporal bone resection.
      However, there were dysfunction included hearing, vestibular and facial nerve.

PMID- 14727429
TI  - [The supplement therapy of microwave after endoscopic maxillary sinus surgery].
AB  - OBJECTIVE: To observe therapeutic effect of microwave eliminating the remnant
      lesion located at walls of maxillary sinus after endoscopic maxillary sinus
      surgery and the effect of postoperative. METHOD: Twenty-six cases (37 sites) were
      treated with microwave coagulating through enlarged ostium completely by means of
      70 degrees endoscopy-guided. RESULT: The remnant lesion located at walls of
      maxillary sinus of 23 cases (33 sites) were eliminated without any complication
      and the effective eliminating rate was 89.2% (33/37). The infected local
      secretion of maxillary sinus of 17 cases (22 sites) were disappeared. CONCLUSION:
      The therapy of microwave by means of nasal endoscopy-guided can get rid of the
      lesion which is located at walls of the maxillary sinus to avoid the trauma
      caused by Caldwell-Luc operation, etc. It can improve the effect of the
      endoscopic sinus surgery.

PMID- 14727431
TI  - [Bilateral total deafness due to mumps and the outcome of cochlear implantation].
AB  - OBJECTIVE: Bilateral deafness due to mumps is rare. Here report three cases of
      bilateral total deafness due to mumps and their outcome of cochlear implantation.
      METHOD: Three cases of bilateral total deafness due to mumps were reviewed.
      RESULT: All patients had sudden bilateral total deafness in 3 to 7 days after
      mumps. 2 had vestibular symptoms. Cochlear implantation has been successful in
      all 3 patients. Three month after the initial mapping, Case 2 who has been
      wearing bilateral hearing aids and received one-year language training has the
      best outcome of hearing and speech than the other two. Case 1 who has been
      wearing one-side hearing aid and received language training of 6 months has the
      better outcome than case 3 who has never worn hearing aid and never received
      language training. CONCLUSION: Hearing loss caused by Mumps is often sudden in
      onset, conservative therapy have no help. Hearing aid and language training are
      very important to the outcome of speech perception and speech production after
      cochlear implantation.

PMID- 14727432
TI  - [Expression of inducible nitric oxide synthase in allergic fungal
      rhinosinusitis].
AB  - OBJECTIVE: To investigate the expression of inducible nitric oxide synthase(iNOS)
      in the mucus involved in allergic fungal rhinosinusitis(AFRS) and chronic
      sinusitis(CRS). METHOD: The iNOS expression was examined using
      immunohistochemistry in cases of AFRS as well as CRS. RESULT: The expression rate
      of iNOS in AFRS was significantly higher than in CRS. CONCLUSION: The increased
      expression of iNOS may involve in AFRS pathogenesis. Statistical difference
      between AFRS and CRS groups may indicate two groups may be distinct diseases
      entity.

PMID- 14727433
TI  - [Determination of platelet activating factor in middle ear effusion of patients
      with secretory oitits media].
AB  - OBJECTIVE: To study the role of platelet activating factor (PAF) in the
      pathogenesis of secretory otitis media (SOM). METHOD: The content of PAF in blood
      plasma and middle ear effusion(MEE) were measured in 56(68years) patients with
      secretory otitis media and in 40 normal subjects respectively by RP-HPLC. RESULT:
      The concentration of PAF in MEE was remarkably higher than those in blood plasma
      (P < 0.01). The concentration of PAF in blood plasma in the SOM group was higher
      than those in the normal control group(P < 0.05). The concentration of PAF of MEE
      in the mucous fluid group was higher than those in the serous fluid group(P <
      0.01). CONCLUSION: PAF might be an important mediator in MEE of SOM, it might be
      closely related to the persistence of SOM, and might play an important role in
      the pathogenesis of SOM.

PMID- 14727434
TI  - [Factors that affect the improvement of olfactory function after endoscopic sinus
      surgery in patients suffering from chronic sinusitis and/or nasal polyps].
AB  - OBJECTIVE: To investigate the factors related to the improvement of olfaction
      after endoscopic sinus surgery (ESS) in chronic sinusitis and/or nasal polyps
      patients. METHOD: Fourteen patients suffering from chronic sinusitis and/or nasal
      polyps were accompanied with olfactory dysfunction. At 6 months after the ESS,
      measurement of olfaction showed that 27 patients' olfaction had improved. The
      effective rate is 61.36%. Using a logistic regression model, we analyzed the
      factors such as gender, disease stage, disease site, allergy, duration of
      olfactory dysfunction and follow-up. RESULT: Contrary to gender, disease site and
      duration of olfactory dysfunction, disease stage, allergy and follow-up had a
      significant effect on the improvement of olfaction. CONCLUSION: In order to
      improve the olfaction of the patients with chronic sinusitis and/or nasal polyps,
      it is important to treat positively with allergic rhinitis on a basis of the ESS.
      Follow-up should be emphasized further.

PMID- 14727435
TI  - [The expression and clinical implication of inducible nitric oxide synthase mRNA
      in laryngeal carcinoma and hypopharyngeal carcinoma].
AB  - OBJECTIVE: To study the expression of inducible nitric oxide synthase(iNOS) mRNA
      in laryngeal carcinoma and hypopharyngeal carcinoma and its clinical
      significance. METHOD: The tissue samples (laryngeal carcinoma, 40; hypopharyngeal
      carcinoma, 12; adjacent tissue, 50; laryngeal papilloma, 10; amyloidosis of
      larynx, 2; and normal laryngeal mucosa, 7) were examined by reverse transcription
      polymerase chain reaction(RT-PCR). RESULT: 1. The target gene of iNOS were
      detected in 41 of 52 tumor tissues, 10 of 50 adjacent tissues, 5 of 12 benign
      tumor tissues and 0 of 7 normal tissues. The difference was significant (P <
      0.0001, P < 0.005, P < 0.0001); 2. No significant difference was found among the
      expression of iNOSmRNA in different primary locations, there was significant
      statistical difference between the early clinical stages (T1-T2) and the advanced
      stages (T3-T4); 3. The poorly differentiated tumor cell showed a higher iNOSmRNA
      expression than that in moderate differentiated tumor cell (P < 0.05) and the
      iNOSmRNA expression in the lymph node metastasis group was higher than the non
      metastasis group (P < 0.05). CONCLUSION: It suggests that iNOS gene expression
      occurs in human laryngeal carcinoma and hypopharyngeal carcinoma, it might
      involve in the development of head and neck neoplasms in gene level by generating
      NO.

PMID- 14727436
TI  - [The different levels of prednisolone in perilymph after local and systemic
      treatment].
AB  - OBJECTIVE: The present study was to analysis the pharmacokinetics of prednisolone
      21-hydrogensuccinate in the perilymph after local and systemic application.
      METHOD: On the local application, 5% prednisolone-21-hydrogensuccinate was
      directly applied into the round window niche under the microscopy. On the
      systemic application, the drug (60 mg/kg) was used intraperitoneal. Perilymphatic
      samples were obtained after variable periods of application. Levels of
      prednisolone-21-hydrogensuccinate in perilymph were measured by using HPLC.
      RESULT: The highest level of the drug was on (952.3 +/- 382.7) mg/L after 180
      min. And remained on (18.72 +/- 16.97) mg/L after 960 min in the local
      application groups. In the systemic application group, the highest level of the
      drug was on(14.71 +/- 7.05) mg/L after 150 min. CONCLUSION: The results
      demonstrate that high levels and long time remain of prednisolone-21
      hydrogensuccinate in perilymph are achievable by a single dose local application
      into the round window niche.

PMID- 14727437
TI  - [Experimental study on olfactory evoked potential in rabbits].
AB  - OBJECTIVE: To observe olfactory evoked potential(OEPs) produced by electrical
      stimulation of the olfactory mucosa and to find out an objective way to appraise
      olfactory function. METHOD: A bipolar stimulus electrode was placed on the
      olfactory mucosa of adult health rabbits via anterior naris. Olfactory evoked
      potential was recorded at headtop after being given a 0.5-4.0 mA current to the
      mucosa. And we also investigated the effect of stimulus parameters and stimulus
      location to the wave form of OEPs. RESULT: Triphasic negative-positive-negative
      evoked potentials were recorded from the surface of the frontal head close to
      olfactory bulb. Latent period of three waves respectively was N(1)20.6 ms,
      P(1)33.5 ms, N(2)58.3 ms. CONCLUSION: In general, the OEPs were composed of
      triphasic negative-positive-negative complexes. The waveforms were stable and
      could be repeated well. Each parameter was useful for estimating the olfactory
      function.

PMID- 14727438
TI  - The maelstrom of civil commitment in Ontario: using examinations conducted during
      periods of unlawful detention to form the basis of subsequent involuntary
      detention under Ontario's Mental Health Act.

PMID- 14727439
TI  - Liquidation of a pharmacy's prescription drug inventory.

PMID- 14727440
TI  - [A paradigmatic glance on nursing care -- a walk to complex care].
AB  - The text addresses the Cartesian paradigms (modern) and the complexity paradigm
      (post-modern of Edgar Morin) aiming to deepen reflection on the theme and
      understanding to improve nursing. To this end, the authors discuss the model of
      care of methodical nursing in the Cartesian paradigm defining it as producer of
      an authoritarian, fragmented and linear care. They point the need to rethink that
      model because it restricts the autonomy of the people/patient moving in the
      direction of complex care that provides for customers/actors' participation in
      their health care planning.

PMID- 14727441
TI  - [Political-academic discourse and integration of handicapped people: from
      appearances to the senses].
AB  - Our aim was to analyze law no. 3.298/99 and course plans in undergraduate nursing
      programs in order to confirm the inclusion of the item for participation of
      nurses in the Handicapped People (HP) integration process. We read the plans of
      courses from four universities; identified the courses in common and distributed
      them according to the level of health care. The proposals of the law are
      universal, equal, and democratic; the plans of courses analyzed adopt most of the
      actions recommended by the Ministry of Health in order to prevent deficiencies.
      Nevertheless, academic practice exercises prevention/treatment of diseases,
      silencing concern over the insertion of nurse in the HP integration process.

PMID- 14727442
TI  - [Nursing care in the anesthesia recovery period: review of the literature].
AB  - The present study was undertaken after it was observed that patients submitted to
      surgical procedures arrived in recovery room with incomplete records, thus
      complicating continuing nursing care. The goal of the present study is to analyze
      bibliographic data from 1990 to 2002 on recovery room nursing care. The data was
      obtained from LILACS (Latin America Literature about Health Science), PERIENF
      (Nursing School Library of the University of Sao Paulo) and BDENF (Library of
      Federal University of Minas Gerais). The key words were nursing care, recovery
      room and immediate post-operative period. Only 16 articles were found, indicating
      a shortage of literature on this topic. The recovery room period is an important
      period of hospitalization and the data are essential for continuous care.

PMID- 14727443
TI  - [In search of the best evidence].
AB  - Evidence-based practice is an approach involving the definition of a problem, the
      search for and critical evaluation of available evidence, the implementation of
      evidence in practice and the evaluation of the results obtained. In order to
      implement this approach in nursing, nurses must know how to obtain, interpret and
      integrate evidence stemming from research in the care rendered to patients and
      their relatives. Based on the literature, this article presents theoretical
      considerations concerning the hierarchy of evidence and where to search for the
      best evidence.

PMID- 14727444
TI  - [Electronic medical prescription at a university hospital: writing failures and
      users' opinions].
AB  - This study analyzed the writing failure of the computerized physician order entry
      system and its advantages and disadvantages according to users. At a university
      hospital 1,351 physician orders were analyzed and 84 nursing and medical
      professionals were interviewed. The results showed that 17.7% of the orders
      presented measures, medication had been suspended in 16.8%, in 28.2% there was
      dubious or misleading information and in 25% medication had been prescribed
      manually. The professionals indicated advantages such as: ease of data reading
      and the quickness with which the order is entered and released, among others.
      They also reported disadvantages such as the repetition of orders from previous
      days without a review and incorrectly typed information. Therefore, it is
      concluded that, despite representing an important strategy for error reduction,
      this system must be overhauled and professionals must be trained to use it.

PMID- 14727445
TI  - [Surgical suture threads and the operating room nurse: forecasting and provision
      criteria according to the nature of hospital institutions].
AB  - The study has identified and described criteria adopted by the nurses in
      selecting and calculating quantities of surgical sutures to supply the Surgical
      Center, according to the public or private nature of the surgical centers. The
      data were collected using structured questionnaires in 74 hospitals within the
      municipality of Sao Paulo. The majority of hospitals are medium in size and
      privately owned with a general Operation Room and up to 500 surgical procedures
      performed per month. The procedures, the type and the variety of surgical sutures
      are related to the nature of hospital management. However, there are no criteria
      to select surgical sutures and their distribution in the operation rooms. The
      nurses participate on the procedures for purchasing, distribution and use of the
      surgical sutures.

PMID- 14727446
TI  - [The interpretative and biographical method for understanding experiences and
      expressions of pregnant women attending a health service].
AB  - This objective of this study based on pictorial ethnography is to understand the
      experience of women in their contact with the health system during pregnancy. The
      data were presented by narrative and their analysis was done based on the
      Interpretative and Biographical Method. From the interviews eight cultural
      categories were taken, from which emerged three cultural themes: "Classification
      of life experiences," "Advancement of the birth process" and "Taking pictures of
      significant events." The findings allowed for a comprehensive vision of the
      participants' cultural knowledge related to their interaction with the health
      system, as well as their expectations of the puerperal gravid cycle.

PMID- 14727447
TI  - [Symbolic meanings of patients with chronic diseases].
AB  - The investigation presents three cultural universes of those suffering from
      arterial hypertension, diabetes and arthrosis, describing the different
      dimensions and interpreting their meaning. The ethnographic method was utilized,
      using the ethnographic interview and participant observation and for the
      interpretation, the symbolic interactionism and other authors. Convergences in
      the dimensions arise in which the three diseases are perceived: the loss of well
      being and social support, fear of disability and death. perception of the family
      and accepting the chronicity, interest in alternative medicine. The informants of
      this study perceive nursing care with ambiguity.

PMID- 14727448
TI  - [Use of phytotherapy in children up to 5 years of age in a central and peripheral
      area of the city of Sao Paulo].
AB  - This research evaluated the use of phytotherapy in children who attend a Health
      Center in an urban area and a Health Center in the suburbs of Sao Paulo city.
      This is an exploratory and descriptive study with 120 mothers who attend two
      Health Centers (60 mothers in the urban area and another 60 in the suburbs),
      during December 2001. After receiving approval from the Ethics Committee, the
      mothers were individually interviewed and it was confirmed that 79 (66%) of them
      frequently used chamomile, fennel and peppermint for the intestinal cramps, flu
      symptoms and to calm their children down. Directions on how and what to use was
      provided mainly by parents and grandparents (57%) and no great differences could
      be found in the use of herbs in the two areas of Sao Paulo.

PMID- 14727449
TI  - [Mental disorders: challenges for the family].
AB  - Using a qualitative methodology (open interviews, story-drawing and thematic
      analysis), we identify and analyze 4 categories (temporal mismatching, guilt,
      conflict and loss) found in the discourse of mothers (and one sister) of
      psychiatric patients receiving treatment at the Center for Psycho-Social Care
      (NAPS) in Ribeirao Preto, SP, Brazil, and also evaluate the importance of such
      categories with a view to understanding the dynamical relationships among mental
      health services, patients and their families.

PMID- 14727450
TI  - [Undergraduate nursing education as an option for nursing technicians and
      assistants].
AB  - The aim of this study was to understand the reasons that lead both nursing
      technicians and assistants to enter undergraduate nursing programs. This study
      was carried out in a teaching hospital in the city of Sao Paulo, under a
      qualitative research perspective, and the methodologies adopted were the Thematic
      Oral History and the Thematic Categorical Analysis. There were eleven
      participants: three nursing technicians and eight nursing assistants.

PMID- 14727451
TI  - [Expected and unexpected absence of the nursing team of a university hospital at
      the university of Sao Paulo, Brazil].
AB  - The objective of this exploratory-descriptive study was to identify expected and
      unexpected absences of the nursing team at the inpatient units of the University
      Hospital at the University of Sao Paulo. Data regarding unexpected absences of
      the nursing staff employees of these inpatient units were assessed on a monthly
      basis for the year 2000. The percentage of the expected absences regarding
      remunerated weekly time off, holidays and vacations corresponded to 19%, 3:9% and
      8.9%, respectively. The survey of percentage of unexpected absences showed a
      variation among indices found in each unit, thus indicating the possibility of an
      excess workload in some inpatient units.

PMID- 14727452
TI  - IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from
      Behcet's disease.
AB  - OBJECTIVE: IL-18 expression and functional activity has been identified in
      several autoimmune and infectious diseases. To clarify the potential role of IL
      18 during pulmonary Behcet's disease (BD), we have explored the capacity of IL-18
      to induce the expression of IFN-gamma. METHODS: We studied bronchoalveolar lavage
      (BAL) from 12 patients with BD, 10 patients with silicosis as the control disease
      and 10 BAL from healthy subjects. BAL fluid, and BAL fluid cell cultures were
      investigated for IL-18 estimation by ELISA. Analysis of IL-18 and IFN-gamma gene
      expression was carried out before and after LPS stimulation. RESULTS: BD patients
      had significantly elevated levels of IL-18 in BAL fluid compared with control
      disease and healthy subjects. Induction of IFN-gamma and IL-18 were observed from
      BD-BAL fluid cells both spontaneously and after LPS stimulation, at higher levels
      compared to silicosis patients and healthy subjects (HC). Spontaneously only BD
      BAL cells expressed IL-18 mRNA and IFN-gamma mRNA. Forty-eight hours after LPS
      stimulation IL-18 mRNA and IFN-gamma mRNA were observed in BD, silicosis and HC
      cells. Recombinant IL-18 induced IFN-gamma production in BD- BAL fluid cells.
      CONCLUSION: Administration of IL-18 induced greater IFN-gamma production in BD
      BAL fluid cells, than in normal BAL fluid cells. Our data indicate that IL-18 up
      regulation is a feature of BD and suggest that IL-18 and IFN-gamma may contribute
      to the local inflammatory response in BD.

PMID- 14727453
TI  - Tumour necrosis factor-alpha gene promoter region -308 and -376 G-->A
      polymorphisms in Behcet's disease.
AB  - OBJECTIVE: Contribution of HLA-B51 to the genetic susceptibility for Behcet's
      disease is well documented and recent studies suggest involvement of other genes.
      Tumour necrosis factor (TNF) genes are located in the vicinity of the HLA-B
      locus. Polymorphisms in the promoter region of TNF-alpha gene has been found to
      be associated with altered TNF secretion, and it may have a prominent role in the
      increased inflammatory responses of Behcet's disease. METHODS: The study group
      consisted of 99 Behcet's disease patients and 96 healthy matched controls. All
      patients fulfilled the International Study Group criteria for Behcet's disease.
      The TNF-alpha -308 and -376 promoter alleles were assigned by the digestion of
      each amplified PCR product with NcoI and TasI enzymes, respectively. RESULTS: No
      significant difference was observed in the distribution of TNF-alpha promoter
      region polymorphisms between patients with Behcet's disease and controls. There
      was no association between the presence of uncommon -308A and -376A alleles and
      the manifestations or severity of Behcet's disease either. The TNF-alpha -308A
      allele and HLA-B*50 was found to be associated in this series of Turkish patients
      and controls. CONCLUSION: The role of TNF-alpha promoter region -308 and -376
      polymorphisms in the pathogenesis of Behcet's disease is not supported by this
      data. The overexpression of TNF-alpha in Behcet's disease may be caused by other
      polymorphisms in the TNF gene or by post-transcriptional mechanisms.

PMID- 14727454
TI  - Onset signs, clinical course, prognosis, treatment and outcome of adult patients
      with Adamantiades-Behcet's disease in Greece.
AB  - OBJECTIVES: To examine the onset signs, clinical course, prognosis, treatment and
      outcome of Adamantiades-Behcet's disease in adult Greek patients during a 10-year
      follow-up period, and to compare the results with those of other series reported.
      METHODS: The studied population consisted of 82 adult patients (54 male and 28
      female) of Greek origin. Patients filled out a standard questionnaire and were
      followed up regularly. The findings during the follow-up of these patients were
      compared with those of other series. RESULTS: The most frequent onset sign was
      oral aphthae, both in our patients and in those of other published series. Eye
      involvement, joint involvement, genital ulcers and skin lesions followed in
      frequency. During a 10-year follow-up differences were observed between men and
      women, with arthritis being more frequent in females compared to males and with
      an overall more severe course in males. Eye involvement occurred earlier than
      neurological and vascular manifestations. A few differences were found in the
      clinical parameters in comparison to previously reported ethnic series. HLA-B51
      positive patients presented an odds ratio of 9.5, the activity index was 5.17 +/-
      2.56 and the mean severity score 5.96 +/- 2.32. Early treatment led to
      improvement of the disease. CONCLUSION: The pattern of Adamantiades-Behcet's
      disease in adult Greek patients provides major similarities when compared to
      patterns in various other national groups.

PMID- 14727455
TI  - Anti-endothelial cell antibodies in Behcet's disease.
AB  - OBJECTIVE: Circulating antibodies that bind to human endothelial cells cultured
      in vitro have been detected in a variety of diseases, including Behcet's disease.
      In this disorder the reported prevalence of AECA has varied widely. One likely
      source of variability is the ELISA assay itself, in which differing conditions
      and reagents have been used in different reports. METHODS: We have re-examined
      the frequency of AECA in 132 Turkish Behcet's patients and 50 healthy Turkish
      controls, comparing several different methods of preparing the target endothelial
      cells. Human umbilical vein endothelial cells (HUVEC) were used either: 1) fresh
      and non-treated, 2) fixed, or 3) TNF alpha-stimulated. All stages of the
      procedures were performed at room temperature. RESULTS: In Behcet's patients,
      using fresh, non-treated HUVEC, 17 of 130 (13.1%) and 9 of 132 (6.8%) sera were
      positive for IgG- and IgM-AECA, respectively. However, among 50 normal controls,
      2 (4.0%) had IgG-positive and 4 (8.0%) had IgM-positive ELISAs under the same
      conditions. The difference in the frequency of positives between patients and
      controls was not statistically significant. Fixed HUVEC and TNF alpha-treated
      HUVEC gave similar results as well. When group means were examined, only the mean
      for IgG-AECA determined with TNF alpha-stimulated HUVEC reached statistical
      significance. CONCLUSION: The discrepancy between our data and earlier reports in
      the literature probably reflects the methodological differences alluded to, and
      highlights the difficulties in interpreting ELISA assays for AECA.

PMID- 14727456
TI  - The prevalence of atopy and atopic diseases in Behcet's disease.
AB  - OBJECTIVE: The prevalence of Th-2 cell-mediated diseases, such as atopic
      diseases, has been noted to be low in Th-1 cell-mediated diseases. This study was
      undertaken to assess the prevalence of atopy and atopic diseases in Behcet's
      disease (BD), a Th-1 cell-mediated disease, and to investigate the clinical
      association between the atopy and the development of severe manifestations in BD.
      METHODS: We examined 70 consecutive BD patients and 113 controls without BD or
      other inflammatory rheumatic diseases. The cumulative history of severe
      manifestations in BD patients was investigated during the disease course. A skin
      prick test was performed in all the subjects, and atopy was defined as present
      when the size of one or more allergen-induced wheals was equal to or larger than
      that caused by histamine. Atopic diseases were defined as present when there were
      relevant responses for atopic diseases on the questionnaires in the subjects with
      atopy. In addition, serum IgE levels and peripheral blood eosinophil counts were
      measured. RESULTS: The prevalence of atopy and atopic diseases was significantly
      lower in BD patients than in controls. Other atopy parameters, such as serum IgE
      levels and peripheral blood eosinophil counts, were also significantly lower in
      BD patients when compared with controls. However, atopy, serum IgE levels, and
      peripheral blood eosinophil counts did not differ significantly between BD
      patients with and without severe manifestations. CONCLUSION: The prevalence of Th
      2 cell-mediated conditions, such as atopy and atopic diseases, appeared to be
      lower in BD, a Th-1 cell-mediated disease. In addition, a Th-1 and Th-2 balance
      may not influence the development of severe manifestations in BD.

PMID- 14727457
TI  - MEFV mutations are increased in Behcet's disease (BD) and are associated with
      vascular involvement.
AB  - OBJECTIVE: A high prevalence of Behcet's disease (BD) among familial
      Mediterranean fever (FMF) patients has been described recently and a weak
      association of BD and certain MEFV gene mutations, originally linked to FMF, has
      been reported in an ethnically mixed population from France. We further
      investigated the presence of MEFV mutations in BD patients from Turkey, a country
      with a high prevalence of both disorders. METHODS: The frequencies of three FMF
      related MEFV mutations (M694V, M680I and V726A) were investigated in BD patients
      (n = 57) by molecular genetic studies using a polymerase chain reaction with the
      ARMS method. All patients fulfilled the International Study Group Criteria for
      the diagnosis of BD and patients with FMF-like symptoms or a chronic inflammatory
      disease were excluded. RESULTS: Fifteen BD patients were found to carry one
      single MEFV mutation (26%), compared to 9.1% in the control group (p = 0.003, OR:
      3.5, 95% CI: 1.6-7.6). Among 20 BD patients with vascular involvement, 11 (55%)
      had MEFV mutations compared to 4 patients (11%) in the non-vascular group (p =
      0.001, OR: 10, 95% CI: 2.5-39.3). M694V was the dominant mutation in our study
      group (11 out of 15 patients with mutated alleles). Six out of 7 female patients
      with vascular involvement carried MEFV mutations in contrast to 5 out of 13 male
      patients (85.7% versus 38.4%, p = 0.07, OR: 0.1, 95% CI: 0.009-1.14). No
      association with other clinical manifestations was observed. CONCLUSION: MEFV
      mutations, originally linked to FMF, may act as a genetic susceptibility factor
      for other inflammatory disorders such as vascular BD.

PMID- 14727458
TI  - Colchicine-induced leukopenia in a patient with familial Mediterranean fever: the
      cause and a possible approach.
AB  - A young patient with familial Mediterranean fever (FMF) developed leukopenia each
      time she took colchicine. However, when she discontinued the drug the white cell
      and the platelets counts increased but she experienced FMF attacks. Later it was
      found that the patient also had concomitant cytomegalovirus (CMV) infection. This
      complex situation posed several diagnostic and therapeutic issues concerning the
      real cause for the leukopenia and the possible approach to take in such
      conditions. We propose that when an essential drug (such as colchicine for FMF)
      causes leukopenia, one should look for concurrent CMV or another viral infection.
      If there is no such infection, it is suggested that the mechanism leading to
      leukopenia be clarified. In the case of bone marrow suppression, colchicine
      should be continued with injections of G-CSF, whereas if the bone marrow is
      hypercellular it is suggested to use steroids and colchicine concomitantly.

PMID- 14727459
TI  - Benign cystic mesothelioma: a rare cause of ascites in a case with familial
      Mediterranean fever.
AB  - Benign cystic mesothelioma (BCM) is a rare neoplasm of the peritoneum, consisting
      of solitary or multiple cysts arising from mesothelial cells. Here we report a
      patient with a previous diagnosis of familial Mediterranean fever (FMF)
      presenting with abdominal distension and ascites which were found to be due to
      BCM. The co-existence of these two entities has not been reported previously.
      Ascites as the presenting feature of BMC is also a rare observation.

PMID- 14727460
TI  - The role of heat shock proteins in Behcet's disease.
AB  - Heat shock proteins (HSP) are highly conserved molecules with scavenger activity
      that are involved in the correct folding of newly synthesized proteins. Increased
      T and B cell activity against 60/65 kD HSP is observed in different ethnic
      populations in Behcet's disease (BD) with both alpha beta and gamma delta T cell
      responses. Although the specificity of these responses is not clear, animal
      models of uveitis treated with either subcutaneous and oral HSP-derived peptides
      suggest a significant role of HSPs in the immunopathogenesis of BD. Recent
      developments in the innate immune system with the description of toll-like
      receptors (TLR) and HSP60 as a ligand for TLR-2 and TLR-4 suggest also the role
      of HSP60 as an endogenous "danger" signal to the immune system with rapid
      inflammatory cytokine release and the enhancement of adaptive Th1-type responses.
      Activation of both innate and adaptive responses with HSPs also fit well into the
      clinical spectrum of BD with both early, limited responses (recurrent ulcers,
      pathergy, etc.) and chronic lesions (posterior uveitis, thrombosis, neuro-BD,
      etc.).

PMID- 14727461
TI  - Familial Mediterranean fever in 2003. Pathogenesis and management.

PMID- 14727462
TI  - Familial Mediterranean fever: is low mortality from tuberculosis a specific
      advantage for MEFV mutations carriers? Mortality from tuberculosis among Muslims,
      Jewish, French, Italian and Maltese patients in Tunis (Tunisia) in the first half
      of the 20th century.

PMID- 14727463
TI  - Multichamber masses and constrictive pericarditis in Behcet's disease.

PMID- 14727464
TI  - Behcet's disease developing in longstanding rheumatoid arthritis.

PMID- 14727465
TI  - Intra-articular anti-tumor necrosis factor alpha antibody in recalcitrant
      arthritis of Behcet's disease.

PMID- 14727466
TI  - Moving ahead in rehabilitation nursing.

PMID- 14727467
TI  - Dealing with aphasia: three simple rules.

PMID- 14727468
TI  - How do you manage the aggressive behavior of cognitively impaired patients?

PMID- 14727469
TI  - Keys to coding the IRF PAI: impairment groups, etiologic diagnosis, comorbid
      conditions and complications.

PMID- 14727470
TI  - Assessing and addressing inappropriate sexual behavior in brain-injured clients.
AB  - Inappropriate sexual comments and behaviors from clients with brain injuries can
      be frustrating, awkward, and time consuming for the nurses who are caring for
      them. Understanding the meaning of these comments and behaviors, as well as
      receiving direction concerning ways to handle the situation can help nurses
      overcome their frustration and improve the quality of nursing care. This article
      examines potential underlying causes of inappropriate sexual behavior, explains
      the behaviors from client, family, staff, and organizational perspectives, and
      begins to look at ways to respectfully and sensitively address the behaviors
      using a model and framework developed by the Sexual Health Service (SHS) at
      Vancouver Hospital and Health Sciences Centre (VHHSC), in British Columbia,
      Canada.

PMID- 14727471
TI  - Families dealing with stroke desire information about self-care needs.
AB  - As hospital lengths of stay have decreased, healthcare professionals have less
      opportunity to fully educate stroke patients and their families regarding self
      care before the patient is discharged home. Consequently, families often need
      continuing education provided to them in outpatient settings. The purpose of this
      study was to identify the self-care needs about which people dealing with stroke
      most frequently want information. Twenty-four people responded to a survey that
      listed 48 self-care needs structured within Orem's universal self-care requisites
      (USCRs). The top five self-care needs about which information was desired were:
      preventing falls; maintaining adequate nutrition; staying active; managing
      stress; and dealing with emotional and mood changes. These needs correlated with
      several of Orem's USCRs. By keeping these needs in mind, healthcare professionals
      can develop better educational materials and provide more pertinent information
      to stroke patients and their families during homecare or office visits, support
      group meetings, or via the Internet.

PMID- 14727472
TI  - Factors influencing referral of cardiac patients for cardiac rehabilitation.
AB  - This study asked the question: Are there differences in the characteristics and
      referral rates of men and women who are referred for cardiac rehabilitation? The
      sample consisted of 203 men (n = 148) and women (n = 55) who were hospitalized
      with at least one cardiac diagnosis and were eligible for Phase II cardiac
      rehabilitation. Hospital records were reviewed to obtain information on gender,
      age, ethnicity, insurance coverage, marital status, employment status, proximity
      to rehabilitation services, transportation availability, concurrent disease
      processes, domestic responsibilities, documentation of referral for cardiac
      rehabilitation, and the attending physician. A survey sent to the patients
      approximately 3 weeks after their discharge from the hospital also addressed
      these variables. Logistic regression analysis indicated only one predictor of
      referral: the gender of the physician. Male physicians were more likely to refer
      patients for cardiac rehabilitation. This finding must be viewed with caution
      because of the small number of female patients and female physicians included in
      the study. The current literature reflects conflicting findings about the
      proposed relationships; therefore, they merit further investigation.

PMID- 14727473
TI  - Perceptions of autonomy in poststroke elderly clients.
AB  - Stroke is one of the leading causes of adult disability. Four million Americans
      are living with the effects of stroke, with one third having mild impairment and
      two-thirds experiencing moderate to severe impairment. The residual effects of
      stroke may include alterations in physiological functioning, cognition, and
      emotional and psychological changes. One of the more treatable psychological
      complications is depression, which has been correlated with impairments to social
      functioning, functional ability, and self-care efficacy. However, most
      researchers still sense that something else may be contributing to poststroke
      depression. One such factor may be an elderly person's perceived impaired ability
      to make choices on his or her own behalf. Thus, the purpose of this research was
      to determine if this perception is related to poststroke depression. We used a
      nonexperimental design with a convenience sample of 20 elderly stroke survivors.
      Each person completed the Beck's Depression Inventory (BDI) and Hertz's Perceived
      Enactment of Autonomy Scale (PEA), to see if there is a relation between these
      two phenomena. Pearson product moment correlation r was utilized evidencing a
      statistically significant, inverse relationship (r = -.79, p < .001) between
      depression scores and the scores obtained on Hertz's PEA scale.

PMID- 14727474
TI  - [Echinococcus granulosus (cystic echinococcosis)].

PMID- 14727475
TI  - [Is the Swiss population gaining body weight? Body mass index in insurance
      applications between 1950 and 1990].
AB  - In this study 4435 insurance applications to the Swiss Life insurance company
      ("Rentenanstalt") by individuals aged 20-39 years from the time period 1950-1990
      were evaluated. Each application contained the self-reported body weight, height,
      and other informations such as martial status or city of residence. For each
      individual the body mass index (BMI) was computed and the prevalence of
      overweight and obesity for each year was calculated using standard definitions.
      This is the first study which tries to determine the prevalence rates of
      overweight and obesity in Switzerland over time. The absolute body weight (kg)
      increased continuously from 1950 to the year 2000. The most pronounced increase
      was seen in individuals (aged 20-29 years) above the 90th percentile of body
      weight and BMI, i.e. already overweight and/or obese individuals showed the
      largest increase in body weight. In men (aged 20-29 years) the prevalence of
      overweight increased between 1980 and 1990 by more than 10% to a prevalence rate
      of 25%. In women (aged 20-29 years) the prevalence of overweight increased
      continuously from 1960 onward and reached a rate of 10.5% in 1990. In the age
      group of the 30-39 years old individuals no change in the prevalence rates was
      observed. These data suggest that there is a trend for an increased prevalence of
      overweight in Switzerland. Since the study sample was not representative for the
      Swiss population the results have to be interpreted with caution only.
      Nevertheless the results are in agreement with the trends in other countries and
      it can be assumed that similar developments do occur also in Switzerland.

PMID- 14727476
TI  - [Topical treatment of blunt-impact soft tissue injuries].
AB  - Studies have shown that topical NSAIDs, e.g. diclofenac, easily penetrate the
      skin barrier to exert local therapeutic activity. In contrast to oral
      administration, plasma levels after application of topical formulations are by
      several magnitudes lower thus explaining the lack of systemic side effects. We
      discuss the clinical relevance of patches containing an NSAID by demonstrating
      the efficacy and safety of a newly developed diclofenac patch in the topical
      treatment of blunt impact soft tissue injuries in a randomised, placebo
      controlled, double blind, multicentre study. The results showed that the
      diclofenac patch was significantly more effective than placebo (p < 0.0001) with
      a significantly faster pain relief. The diclofenac patch was well tolerated. It
      might be used in indications with similar pathomechanisms.

PMID- 14727477
TI  - [Eosinophilia in a family from Bosnia].
AB  - We describe reference to a family from Bosnia that the diagnosis of
      Trichinellosis can be difficult despite notice of travel-history and eosinophilia
      but lack of further epidemiological datas and due to the rarity of this zoonosis.
      Clinical pattern of trichinellosis are fever, headache, myalgia, periorbital
      oedema, less frequently diarrhea and abdominal pain. Dreaded complications are
      myocarditis and encephalitis. High eosinophilia and increased creatine
      phosphocinase activity are the most frequently observed laboratory features. The
      detection of specific circulating antibodies or the parasitological examination
      of a muscle biopsy will confirm the diagnosis. The medical treatment includes
      albendazol and steroid.

PMID- 14727478
TI  - [Severe hemolytic anemia for the first time in a 42-year-old patient. Homozygote
      G-6-PD deficiency in a woman].

PMID- 14727479
TI  - [Essential osteolysis].

PMID- 14727480
TI  - [Clinical manifestations in acute Lyme diseases].
AB  - Analyzing the clinical observations of 1343 patients, made in the Kama river
      region in 1991 to 2002, could establish a number of characteristic syndromes of
      the acute period of Ixodes tick-borne borreliotosis (ITBB). The early period of
      the diseases manifested itself as two forms: erythematous in 1041 (77.5%)
      patients and erythema-free in 302 (22.5%). The erythematous form was
      characterized by the occurrence of the major clinical marker--erythema migrans at
      the site of tick suction. In Russia, the clinical features of the acute phase of
      borreliotosis were marked by the early (at weeks 2-3 of the disease) affliction
      of different organs (the liver) and systems (the nervous, cardiovascular, and
      locomotor ones). The leading clinical types of the erythema-free ITBB were
      neurological, arthromyalgic, influenza-like, cardiovascular, hepatitis, regional
      lymphadenitis, and mixed. The diagnosis of ITBB is established on the basis of a
      characteristic epidemiological history, clinical manifestations by taking into
      account the most common types of its early period and the data of a serological
      survey by the proposed algorithm.

PMID- 14727481
TI  - [Epidemiology of co-existing opisthorchiasis with Ixodes tick-borne infections on
      Tiumen region].

PMID- 14727482
TI  - [Toxocariasis: spread and impact on reproductive health].
AB  - To study the prevalence of toxocariasis and its impact on the reproductive health
      of inhabitants in the Saratov Region, enzyme immunoassay was used to examine 1404
      patients, including 210 children, 912 females, and 282 males. Toxocariasis was
      shown to be a risk factor of male (oligoasthenozoospermia) and female
      (tuboperitoneal) infertility. The high incidence of toxocariasis in females with
      reproductive dysfunction (recurrent abortion) and an aggravated obstetric history
      complicated by chronic renal diseases is indicative of the existence of the
      urogenital form of toxocariasis. Toxocariasis greatly increases a risk of giving
      birth to a baby with clinical manifestations of intrauterine infection (IUI),
      promotes homeostatic disorder and the formation of long-term pathology in babies
      with IUI. At the same time, there was a significant relationship of abnormal
      cardiotocograms to toxocariasis and to the presence of Trichomonas, Mycoplasma,
      Chlamydia, and Cytomegalovirus.

PMID- 14727483
TI  - [Methodological assurance of natural and drinking water parasitic control].
AB  - The paper shows it necessary to exercise control over the quality of natural,
      waste, and portable water in terms of parasitological indices. The standard
      techniques of sampling and sanitary and parasitological studies of water, which
      allow water quality control to be effectively exercised in accordance with the
      current sanitary regulations, are considered.

PMID- 14727484
TI  - [Infection of coastal catching fishes with a nematode of Anisakis simplex (Rud.,
      1809), L. in the Primor'e region].
AB  - The paper presents data on the infection of fishes from the Gulf of Peter the
      Great with an A. simplex nematode. A total of 308 fishes of 19 species were
      examined for parasites. Of them 5 species were found to be free from nematodes.
      The highest infection rates were noted in fishes of the species Oncorhynchus
      keta, Hexagrammos octogrammus, and Theragra chalcogramma. Differences in the
      infection rates of fishes of the gulf were explained by the specific features of
      their vital activity and by the saturation of the environment with an invasive
      agent. Based on the infection of secondary intermediate hosts with the nematoda,
      it may be suggested that there are the populations of fishes whose
      representatives accomplish their life cycle under the conditions of the internal
      waters of the gulf. The infection rate of these fishes with the parasite is low.
      The altered situation--an increase in the invasion rate--was associated with the
      seasonal migration of fishes of these species from the open marine spaces to the
      cost of the Gulf of Peter the Great. The opposite values of the infection rates
      of deep-sea (herrings) and bottom-dwelling (bases, greenlings) fishes make it
      possible to assume that bottom-dwelling invertebrates function as the first
      intermediate hosts in the life cycle of the nematode.

PMID- 14727486
TI  - [A response of the biota to climatic warming on Europe].
AB  - Data on the impact of climatic warming on a number of phenomena in the life of
      plants, animals, biocenoses, and parasitic systems of transmissible diseases are
      presented. Emphasis is laid on the ambiguity of responses shown by species to the
      same exposures, which makes any forecasting of the consequences of climatic
      warming very difficult, frequently unrealistic and hence it is necessary to
      arrange an epizootological monitoring of malaria and other transmissible
      diseases.

PMID- 14727485
TI  - [Anti-trichuriasis activity of the agents G-1730 and G-1732].

PMID- 14727487
TI  - [Influence of climatic changes on the spread of malaria in the Russian
      Federation].
AB  - The climatic temperature conditions of the atmospheric surface layer in the given
      point of geographic space are considered in this paper to be favourable for human
      malaria if the number of years whose temperature conditions allow the causative
      agent to complete sporogony in the vector if only once is at least 90%. In
      another case, the conditions are considered to be unfavourable. This model
      criterion determines the potential region of the disease. The diagrammatic maps
      depicting such potential regions, as well as their changes in the period of 1966
      1995 as compared to the period of 1936-1965, are given in this paper for tertian
      (P. vivax) and tropical (P. falciparum) malaria. The threshold empirical
      relationship of sporogony success to the variations of the mean diurnal
      temperature in a specific year and the series of diurnal data of meteorological
      observations made for many years at 223 weather stations situated on the
      territory of the former USSR. An analysis shows that there has been a slight
      increase in the regions in Asian Russia for 30 years while there has been a just
      more noticeable reduction in them in European Russia. By and large the changes in
      the regions may be regarded as just moderate.

PMID- 14727488
TI  - [The state of the art of studies of natural and focal infections in the
      Ul'ianovsk region and its frontier areas in the middle Volga region].

PMID- 14727489
TI  - [Intestinal parasitic cenoses in children from closed children institutions and
      prophylactic measures].

PMID- 14727491
TI  - [The epidemiological situation due to parasitic diseases in Zhitomir region].

PMID- 14727490
TI  - [Prevalence if giardiasis in Volgograd city population].
AB  - Analyzing many year's data on the prevalence of giardiasis among Volgograd
      dwellers indicated that the five-year infectivity index did not substantially
      change and it was 6.3 +/- 0.4%. The rate of Giardia lamblia isolation was higher
      in healthy individuals in the high-loaded environmental topodemic regions of the
      city than in those in the good ones. Over 50% of all the cases of giardiasis were
      recorded among 7-15-year-old children, the proportion of preschool children was
      much less (31.9%). The rate of giardiasis detection in children who went to
      children's preschool facilities was twice higher than that in the unorganized
      population. The focality index was 6.8%, which is indicative of the low
      contagiousness of the disease.

PMID- 14727492
TI  - [Hymenolepiasis preventing measures in the population of Ivanovo-Frankovsk].
AB  - The authors review of researches into the influence of socioeconomic factors of
      development of the town (migration, urbanization, etc.) on the formation or
      reduction of hymenolepidosis foci. Emphasis is laid on various influences of the
      above factors on the distribution of hymenolepidiasis. The importance of
      helminthic control is well underlined. Annual medical examination of the whole
      population is considered to be the main prophylactic measure introduced into
      computer educational programs. The problems to be immediately solved by health
      administrators are outlined.

PMID- 14727494
TI  - Holistic nursing and spiritual healing.

PMID- 14727493
TI  - [Dirofilariasis (D. repens) in the Russian Federation and some of the
      Commonwealth of Independent States countries: situation and trends].

PMID- 14727495
TI  - Echinacea fails to show efficacy in treating colds in a pediatric population.

PMID- 14727496
TI  - Coenzyme Q-10 and cardiovascular health.

PMID- 14727497
TI  - Experience and attitudes towards CAM--a survey of internal and psychosomatic
      patients in a German university hospital.
AB  - Complementary and alternative medicine (CAM) is popular in Germany. In a
      consecutive survey the experiences with CAM and the need for a CAM consultation
      among inpatients of the departments of cardiology (CL), gastroenterology (GE),
      oncology (OL) and psychosomatics (PS) of the University Hospital Freiburg (FUH)
      were questionned. Exclusion criteria were inability to understand the questions
      or a Karnofsky Index < 30%. Four hundred thirty-five patients were included.
      Three hundred and fifty patients, 100 each in the departments of CL, GE and OL,
      and 50 in PS answered the questionnaires. Eighty-five patients (20%) refused.
      Among the 350 patients 26% had previously visited a CAM physician and 19% had
      visited a CAM therapist (Heilpraktiker). Information about CAM was obtained
      mainly by television, radio and family members. Frequently used therapies for the
      current disease were physical training (21%), diet (19%), massage (19%),
      vitamins/trace elements (19%), herbs (13%), acupuncture (10%) and homeopathy
      (7%). The highest frequency of CAM use had PS patients, followed by GE, OL and CL
      patients. High effectivity (> or = 70%) for the current disease, rated on a scale
      of 4 degrees, had for CL patients physical exercise and massage, for GE patients
      herbal treatment and for OL patients diet. Physical exercise, diet, massage and
      herbal treatment generally had better ratings than homeopathy, acupuncture and
      vitamins. 65% would welcome a CAM center and 53% asked for a consultation about
      CAM at FUH. OL and GE patients had the strongest (58%), PS patients a lower (52%)
      and patients with cardiovascular diseases the lowest (43%) interest in a CAM
      consultation. Twenty-five percent believed, that CAM can help to cope better with
      their disease. Predictors for a positive attitude towards CAM were young age,
      aversion to chemical medications (Spearman correlation r = 0.22), desire to
      participate in therapeutic decisions (r = 0.29), motivation to change, if
      recommended, the life style (r = 0.31) and desire for a holistic treatment (r =
      0.37).

PMID- 14727498
TI  - Transcutaneous electrical acustimulation can reduce visceral perception in
      patients with the irritable bowel syndrome: a pilot study.
AB  - OBJECTIVES: Acupuncture has been used as a therapy for various gastrointestinal
      disorders, including irritable bowel syndrome (IBS). However, there is scant
      information on the effect of acupuncture on gut physiology. The purpose of this
      study was to evaluate the effect of transcutaneous electrical acustimulation
      (TEAS) on rectal tone, compliance and perception in IBS patients. METHODS: Seven
      patients with diarrhea-predominant IBS were studied during control, sham
      stimulation and acupoints (ST36 and P6) stimulation periods. Rectal tone,
      compliance and perception to rectal balloon distension were assessed with a
      barostat apparatus. RESULTS: Acustimulation at ST36 and P6, but not sham
      stimulation, significantly increased the threshold of rectal sensation of gas,
      desire to defecate and pain, as compared to control period. However, rectal tone
      and compliance were not significantly affected during TEAS. CONCLUSIONS: TEAS, at
      the above acupoints, can reduce rectal sensitivity in IBS patients. The effect is
      not modulated by changes in rectal biomechanics.

PMID- 14727499
TI  - Ayurveda for diabetes mellitus: a review of the biomedical literature.
AB  - Diabetes mellitus is a condition that is extremely serious from both clinical and
      public health standpoints. The traditional healthcare system of India, Ayurveda,
      offers a balanced and holistic multi-modality approach to treating this disorder.
      Many Ayurvedic modalities have been subjected to empirical scientific evaluation,
      but most such research has been done in India, receiving little attention in
      North America. This paper offers a review of the English language literature
      related to Ayurveda and diabetes care, encompassing herbs, diet, yoga, and
      meditation as modalities that are accessible and acceptable to Western clinicians
      and patients. There is a considerable amount of data from both animal and human
      trials suggesting efficacy of Ayurvedic interventions in managing diabetes.
      However, the reported human trials generally fall short of contemporary
      methodological standards. More research is needed in the area of Ayurvedic
      treatment of diabetes, assessing both whole practice and individual modalities.

PMID- 14727500
TI  - Complementary and alternative medicine use by women after completion of
      allopathic treatment for breast cancer.
AB  - CONTEXT: A growing number of women are being diagnosed and successfully treated
      for breast cancer. Therefore, many women are living with a history of breast
      cancer. The use of complementary and alternative therapies within this patient
      population has increased. OBJECTIVE: To determine post breast cancer treatment
      health behaviors with regard to use of complementary and alternative therapies.
      DESIGN: Survey participants were asked about their use of 15 complementary and
      alternative medicine (CAM) therapies. In order to determine the relative
      importance of the hypothesized predictor variables, standard logistic regression
      was performed with CAM use as the dependent variable. PARTICIPANTS: 551 women who
      had been diagnosed with breast cancer and were post treatment. INTERVENTION:
      Telephone Survey. RESULTS: Telephone interviews were conducted with 551 females
      in the Portland, Oregon, metropolitan area who had been diagnosed with breast
      cancer an average of 3.5 years earlier. Two-thirds (66%) of the women used at
      least one CAM therapy during the previous 12 months, and the majority of them
      perceived that their CAM use was without the recommendation of their doctor.
      Relaxation/meditation, herbs, spiritual healing, and megavitamins were used most
      often. Significant predictors of CAM use included younger age, higher education,
      and private insurance. The majority of the CAM therapies were perceived by their
      users to be at least "moderately important" in remaining free of cancer. The
      reasons given for using CAM were to enhance overall quality of life, to feel more
      in control, to strengthen the immune system, and to reduce stress. CONCLUSIONS:
      Two-thirds of women in this study followed conventional treatment for breast
      cancer with one or more CAM therapies, which, they believed, could prevent cancer
      recurrence and/or improve their quality of life. CAM use did not reflect negative
      attitudes towards conventional medical care, but rather an orientation to self
      care in the optimization of their health and well being.

PMID- 14727502
TI  - Edward Tick, PhD: On Asklepios, dream healing, and talking with the dead.
      Interview by Bonnie Horrigan.

PMID- 14727503
TI  - Poison or medicine? A note from the forest.

PMID- 14727501
TI  - The variability of TCM pattern diagnosis and herbal prescription on rheumatoid
      arthritis patients.
AB  - CONTEXT: The consistency of diagnosis made among Traditional Chinese Medicine
      (TCM) practitioners and the relationship between TCM diagnosis and Chinese herbal
      prescription have not been adequately examined. OBJECTIVE: To investigate the
      degree of consistency with which TCM diagnoses and herbal prescriptions can be
      made by practitioners examining rheumatoid arthritis (RA) patients. To survey TCM
      diagnostic patterns and to examine the correlation between herbal prescriptions
      and these diagnoses for a sample of RA patients. DESIGN: A prospective survey.
      SETTING: General Clinical Research Center, University of Maryland Hospital
      System, Baltimore, MD. PATIENTS: Rheumatoid arthritis patients. PRACTITIONERS:
      Licensed acupuncturists with a minimum of 5 years licensure and education in
      Chinese herbs. METHODS: Three TCM practitioners examined the same 39 RA patients
      separately, following the traditional "Four Diagnostic Methods." Patients filled
      out a questionnaire to serve as the data for the "Inquiry" component. They then
      underwent a physical examination, including the tongue and pulse, conducted by
      each of the practitioners. Based upon the examination results, each practitioner
      provided both a TCM diagnosis and a herbal prescription. These
      diagnoses/prescriptions were then examined with respect to the rate of agreement
      among the 3 practitioners. RESULTS: The average agreement with respect to the TCM
      diagnoses among the 3 pairs of TCM practitioners was 28.2% (25.6 to 33.3% with
      kappas ranging from 0.23 to 0.30). The degree to which the herbal prescriptions
      agreed with textbook recommended practice of each TCM diagnosis was 93.2% (range
      = 87.2 to 100%). CONCLUSION: The total agreement on TCM diagnosis on RA patients
      among 3 TCM practitioners was low. When less stringent, but theoretically
      justifiable, criteria were employed, greater consensus was obtained among the 3
      practitioners. The correspondence between the TCM diagnosis and the herbal
      formula prescribed for that diagnosis was high, although there was little
      agreement among the 3 practitioners with respect to the herbal formulas
      prescribed for individual patients.

PMID- 14727504
TI  - The philanthropic collaborative for integrative medicine: partnering for health
      and healing.

PMID- 14727505
TI  - Successful treatment of post traumatic stress disorder and chronic pain with
      paraspinal square wave stimulation.
AB  - OBJECTIVE: To determine if Paraspinal Square Wave Stimulation (PSWS) is effective
      in treating Post Traumatic Stress Disorder (PTSD) and or Chronic Pain. METHOD:
      PSWS is applied to the paraspinal area from the craniocervical junction to the
      lower sacrum. RESULTS: Patient achieved dramatic relief from PTSD, unequaled by
      any previous pharmacologic or psychotherapies. The chronic pain is almost
      completely disappeared, unlike any previous therapies. CONCLUSION: PSWS is the
      treatment of choice for this patient with PTSD and Chronic Pain. This patient
      appears to have completely recovered from PTSD, unlike any other study reported
      so far.

PMID- 14727507
TI  - [Therapeutic gene clusters as drug action mechanisms].
AB  - Pharmacogenomics is defined to identify the therapeutic gene clusters which are
      involved in determining the responsiveness and to distinguish responders and non
      responders to a given drug. Genome sequencing, transcriptome, proteome and
      metabolome analysis are of particular significance in pharmacogenomics.
      Sequencing is used to locate polymorphisms, and monitoring of functional gene
      expression can provide clue about the genomic response to disease and treatment.
      The transcriptome analysis can be done by methods of random cDNA sequencing, mRNA
      display(fluorescent differential display et al.) and differential
      hybridization(cDNA microarray, oligomicrochip et al.). We used
      transcriptome/proteome/metabolome analysis to identify therapeutic target genes
      by studying change of gene expression in animal models and human model cells of
      various diseases and found novel drug target candidates through this
      pharmacogenomic strategy. The present study describes combined transcriptome and
      metabolome analysis for therapeutic target validation in hypoxia-induced vascular
      remodeling. The pharmacogenomic analysis and pharmainformatics has the potential
      for strategy to define novel therapeutic gene clusters in various diseases and
      holds the promise that drugs might be tailor-maid for individuals and adapted to
      each person's own genetic makeup. These techniques provided an excellent strategy
      for screening and validation of targets.

PMID- 14727506
TI  - [Altered behavioral response to centrally acting drugs in mice lacking PACAP].
AB  - Mice lacking PACAP (PACAP-KO) exhibits altered psychomotor behaviors, including
      impaired habituation to a novel environment and perseverative jumping, with a
      slightly reduced levels of the serotonin metabolite, 5-HIAA, in the brain. We
      have recently demonstrated that PACAP-KO exhibits abnormalities in sensorimotor
      gating as measured by prepulse inhibition (PPI) of the acoustic startle. In the
      present study, behavioral responses to centrally acting drugs (amphetamine,
      haloperidol, risperidone, fluoxetine, and 8-OH-DPAT) were examined in PACAP-KO.
      Surprisingly, a psychostimulant amphetamine effectively normalized the deficit in
      PPI as well as hyperactivity and jumping behavior. These results implied
      phenotypic and pharmacological similarity between PACAP-KO and attention deficit
      hyperactivity disorder (ADHD). Although a potent dopamine D2-like receptor
      antagonist, haloperidol, ameliorated the hyperactivity and jumping behavior, it
      had no effect on the deficit in PPI. In contrast, a prototype of serotonin
      dopamine antagonist (SDA), risperidone, effectively normalized the deficit in PPI
      as well as hyperactivity, and jumping behavior. A selective serotonin reuptake
      inhibitor (SSRI), fluoxetine, also suppressed the hyperactivity and jumping
      behavior. A 5-HT1A receptor agonist, 8-OH-DPAT, significantly lowered rectal
      temperature in wild-type mice, while it had only a small effect in PACAP-KO.
      These results suggest the involvement of dopaminergic and serotonergic
      dysfunction in phenotypic changes observed in PACAP-KO.

PMID- 14727508
TI  - [Adrenergic receptor signaling and regulation].
AB  - At the beginning, beta-arrestin is believed to regulate desensitization of G
      protein-coupled receptors. However, it becomes apparent that beta-arrestin is
      involved in not only regulation but also signal transduction by identification of
      many proteins interacting with beta-arrestin. So far, the model of regulation and
      signaling of G protein-coupled receptor is built on beta 2-adrenergic receptor.
      However, this model does not apply to all G protein-coupled receptors. The
      differential regulation and signaling between beta 1- and beta 2-adrenergic
      receptors is presented.

PMID- 14727509
TI  - [Molecular pharmacology of sarpogrelate].
AB  - Sarpogrelate, a 5-HT2A antagonist, is used clinically as a therapeutic agent for
      ischemic blood vessels. Thus, the present study was designed to evaluate the
      selectivity to 5-HT2 subtypes, to assess the pharmacological effect using porcine
      coronary arteries and to demonstrate the identification of the binding sites
      using molecular modeling. Sarpogrelate was higher selectivity to 5-HT2A than
      those of ketanserin, ritanserin or cyproheptadine and these results were
      supported by the computer modeling.

PMID- 14727510
TI  - [Functional expression of machineries for glutamate signaling in bone].
AB  - RT-PCR analysis revealed expression of mRNAs for particular GluRs, Glu
      transporters and vesicular Glu transporter in primary cultures of rat calvarial
      osteoblasts under premature to mature states. Sustained exposure to the NMDA
      receptor antagonist MK-801 significantly prevented increases in alkaline
      phosphatase activity, Ca2+ accumulation and DNA binding activity of CBFA1 in a
      concentration dependent manner in osteoblasts cultured for 7 to 28 DIV, without
      significantly affecting cell survivability. The agonist for group III mGluR L-AP4
      significantly inhibited the accumulation of cAMP induced by parathyroid hormone
      in osteoblasts, which occurred in a manner sensitive to prevention by the group
      III antagonist CPPG. AMPA significantly increased the release of endogenous Glu
      from osteoblasts in the presence of the inhibitor of AMPA receptor
      desensitization cyclothiazide. The release evoked by AMPA was significantly
      prevented by the addition of an AMPA receptor antagonist as well as the removal
      of Ca2+ ions. [3H]Glu uptake was also seen in a temperature- and sodium-dependent
      manner in cultured osteoblasts. These results suggest that Glu may at least in
      part play a role in mechanisms associated with cellular proliferation and/or
      differentiation through particular GluR and Glu transporters functionally
      expressed in rat calvarial osteoblasts.

PMID- 14727511
TI  - [Modulation of excitability in midbrain dopaminergic neurons and skeletal muscles
      by neuronal nicotinic receptors: perspectives from knockout mice].
AB  - Neuronal nicotinic receptors (nAChRs) are widely expressed in the central and
      peripheral nervous systems, and also found in several non-neuronal tissues,
      including skeletal muscles. Since neuronal nAChRs possess a high Ca2+
      permeability, we investigated the mechanisms of intracellular Ca2+ mobilization
      through nAChR in midbrain dopaminergic neurons and skeletal muscles, using alpha
      7-/- or beta 2-/- mice. RT-PCR study showed the existence of alpha 7 mRNA in
      denervated muscles of wild-type mice. Choline (alpha 7 agonist) elicited a muscle
      depolarization, but this component was abolished in alpha 7-/- mice. These
      suggest that alpha 7-nAChR up-regulated in denervated muscle may contribute to
      regeneration of the damaged neuromuscular synapse. Moreover, fura-2-imaging
      analyses in midbrain slices demonstrated that nicotine-elicited Ca2+ mobilization
      was diminished in beta 2-/- mice. The Ca2+ mobilization was markedly inhibited by
      dantrolene. Therefore, the Ca2+ influx due to beta 2-nAChR activation appears to
      be amplified by the recruitment of intracellular Ca2+ stores. To regulate unusual
      nAChR functions in neurological diseases, the search for new and selective
      ligands has continuously increased. We examined the effects of frog alkaloids on
      nAChRs expressed in Xenopus oocytes, and found that indolizidines 235B'
      selectively blocked alpha 4 beta 2-nAChR. Thus, the approach based on natural
      products can still provide a great advantage for producing novel therapeutics.

PMID- 14727512
TI  - [Signal transduction and development of drug for brain ischemic insult].
AB  - The author reported that sodium orthovanadate rescues cells from delayed neuronal
      death in gerbil hippocampus after transient forebrain ischemia though
      phosphatidylinositol 3 kinase/Akt pathway. We here demonstrated that the
      activation of FKHR, a Forkhead transcription factor and a substrate for Akt,
      precedes the delayed neuronal death in CA1 regions after transient forebrain
      ischemia. The phosphorylation of FKHR at serine-256 in the CA1 region decreased
      immediately after reperfusion. The dephosphorylation of FKHR was correlated with
      the decreased Akt activity. Intracerebroventricular injection of orthovanadate 30
      min before ischemia inhibited dephosphorylation of FKHR after reperfusion, and
      block delayed neuronal death in the CA1 regions. Two days after reperfusion,
      expression of Fas ligand increased in the CA1 region and the orthovanadate
      injection inhibited this increased expression. Furthermore, sublethal ischemia
      gradually and persistently stimulated the phosphorylation of Akt-Ser-473 in the
      CA1 region after reperfusion. The preceded sublethal ischemia prevented the
      delayed neuronal death induced by the lethal ischemic conditions.
      Intracerebroventricular injection of wortmannin before preconditioning blocked
      both the increased in Akt-Ser-473 phosphorylation and the neuroprotective action
      of preconditioning. These results suggested that the inactivation of Akt results
      in the activation of FKHR and, in turn, relates to the expression of Fas ligand
      in the hippocampal CA1 region after transient forebrain ischemia. The prevention
      of Akt inactivation by treatment with orthovanadate is a potential therapeutic
      strategy for neuroprotection in brain ischemic insult. Thus PI3-kinase/Akt
      pathway and its downstream molecules are potential targets for drug development
      in the brain ischemic insult.

PMID- 14727513
TI  - [Probing of the target molecules of Rho-kinase and its function in neuronal
      cells].
AB  - Genome project terminated and post-genome project started, one of which aim is to
      understand the function and its regulation mechanism(s) of the molecules in
      living cells. Protein phosphorylation is one of the most common reactions
      responsive to extracellular stimulants. It is well understood about the
      involvement of Rho/Rho-kinase and Cdc42/p21-activated kinase (PAK) in the
      functions of muscle and non-muscle cells, but in neuronal cells little or poorly
      is understood. This is due to poor evidences about the target molecules of Rho
      kinase and PAK and its functions in neuronal cells. We have revealed using a
      phosphorylation site-specific antibody that PAK targets synapsin Ia at Ser603 in
      vitro and in neuronal cells in culture, which is recognized as CaMKII site. This
      is reasonable, because the 600RQAS603 around Ser603 is also consensus motif for
      the phosphorylation of PAK and Rho-kinase besides CaMKII. Like this, we have
      tried to define the target molecules of Rho-kinase in neuronal cells. In this
      symposium, I would present that both Rho-kinase and PAK target MARCKS at Ser159
      in vitro and in neuronal cells stimulated with LPA and bradykinin, respectively.
      Moreover, we would address the role of phosphorylation of MARCKS at Ser159 in
      neuronal functions.

PMID- 14727514
TI  - [Functional differentiation of neural stem cells into endothelial cells].
AB  - Neural stem cells (NSCs) were isolated from mouse embryonic day 12.5 (E12.5)
      cortex and cultured by neurosphere formation in serum-free medium in the presence
      of 20 ng/ml basic fibroblast growth factor (bFGF). To examine whether NSCs give
      rise to endothelial cells, differentiation was induced by the addition of 10%
      fetal bovine serum (FBS) after bFGF withdrawal. Most of the differentiated cells
      displayed a cobblestone-like morphology. Immunological analyses and RT-PCR
      indicated that NSCs expressed endothelial cell-specific marker proteins such as
      PECAM-1, VE-cadherin, and Flk-1, and these expressions were up-regulated during
      differentiation. When the differentiated cells were inoculated in collagen gels
      with 10% FBS and bFGF and incubated for 5 days, vessel-like tube structures
      consisting of PECAM-1- or VE-cadherin-immunoreactive cells were formed in the
      gels. These results suggested that NSCs give rise to endothelial cells in vitro,
      which have the ability to form vascular tubes.

PMID- 14727515
TI  - [Functional analysis of SIR2].
AB  - The yeast silent information regulator 2 (Sir2) is an NAD-dependent histone
      deacetylase and silences transcription at the mating type loci, telomeres and the
      ribosomal DNA. Over-expression of Sir2 extends the life span of yeast and C.
      elegans, while Sir2 knockout shortened yeast life span to about 50%. Mammalian
      cells also express several Sir2 homologues. However, most of physiological
      functions of Sir2 homologues seem to be unknown. We found that Sir2 alpha (SIRT1)
      was highly expressed during embryogenesis. In the adult mouse brain, ependymal
      cells and some cells of subventricular zone expressed Sir2 alpha. To identify
      proliferating neural cells in the adult brain, BrdU was administered in the
      drinking water for 2 weeks. BrdU-positive and nestin-positive cells expressed
      Sir2 alpha. Furthermore, neurosphere cultured from E14 mouse striatum expressed
      Sir2 alpha. The expression of Sir2 alpha in neurosphere disappeared after
      differentiation. Nicotinamide, splitomicin and sirtinol, potent inhibitors of
      Sir2 alpha, inhibited the growth of neurosphere. FACS analysis showed that
      sirtinol did not increase sub-G1 population of cells. Differentiation of
      neurosphere into neuron and oligodendrocyte was inhibited by the addition of
      nicotinamide, splitomicin or sirtinol in the differentiation medium. These
      results suggest that Sir2 alpha has a pivotal role in the proliferation and
      differentiation of neural stem cells.

PMID- 14727516
TI  - [Mechanical stress and cerebrovascular response--resemblance to cerebral
      vasospasm after subarachnoid hemorrhage].
AB  - The autoregulatory mechanism, including myogenic response, so-called "Bayliss
      effect", is well developed in the brain circulatory area, where also, cerebral
      vasospasm is often encountered after subarachnoid hemorrhage. In the cerebral
      artery smooth muscle, protein kinases, such as Rho-associated kinase, tyrosine
      kinase, and protein kinase C, are activated in response to mechanical stresses,
      including stretch, pressure and flow. All of these kinases are also activated in
      due course of time after development of the vasospasm. Myogenic response is a
      kind of reception and subsequent reaction to mechanical stress, whereas cerebral
      vasospasm is primarily caused by oxyhemoglobin, i.e., oxidative stress. Thus both
      myogenic and vasospastic episodes imply a common stress-responding mechanism. It
      seems possible that various kinases activated by mechanical stress act as not
      only a physiological signaling but also a proatherogenic/remodeling one. The
      stiffness of vasospastic artery was enormously increased in particular in the
      late phase of vasospasm, indicating the augmented process of pathologic
      remodeling. Therefore, "Bayliss effect" in modern sense and cerebral vasospasm
      can be argued in terms of a stress-reaction of cerebral artery.

PMID- 14727517
TI  - [Molecular mechanisms for cAMP-independent activation of MaxiK channel: G protein
      direct channel regulation and contribution to the tuning of vascular smooth
      muscle tone].
AB  - MaxiK channel, the large conductance Ca(2+)-sensitive K+ channel, is expressed
      abundantly in vascular smooth muscles and plays a key role in the tuning of their
      excitability and contractility. The present study was carried out to elucidate
      the contribution of MaxiK channel to prostacyclin receptor (IP receptor)-mediated
      vascular relaxation with a special reference to the role of cAMP. An IP agonist,
      beraprost, induced a strong relaxation in de-endothelialized guinea pig thoracic
      aorta, which was almost abolished by a MaxiK channel selective blocker,
      iberiotoxin (IbTx). Beraprost produced a 30-fold rise in tissue cAMP contents. In
      addition, beraprost-induced relaxation potentiated in the presence of Ro-20-1724
      (a selective inhibitor of cAMP-specific phosphodiesterase) was completely
      counteracted by IbTx. However, beraprost-induced relaxation was not affected by
      SQ22,536, an adenylyl cyclase inhibitor, which abolished this IP agonist-induced
      elevation of cAMP contents. SQ22,536-insensitive relaxant component was
      significantly inhibited by IbTx. Cholera toxin, a Gs activator, qualitatively
      mimicked the effects of beraprost. Furthermore, MaxiK channel currents in aortic
      myocytes were increased by beraprost in a GTP-dependent manner. These results
      indicate that both cAMP-dependent and -independent pathways contribute to MaxiK
      channel-mediated vascular relaxation following IP receptor stimulation. Direct
      regulation by Gs seems to partly account for MaxiK channel-mediated, cAMP
      independent mechanism.

PMID- 14727518
TI  - [Possible involvement of IGF-1 receptor and IGF-binding protein in insulin
      induced enhancement of noradrenaline response in diabetic rat aorta].
AB  - The aim of the present study was to investigate the link between the changes in
      vascular responsiveness associated with hyperinsulinemia in established STZ
      induced diabetes and the growth factors signal system. We have shown that in rats
      with established diabetes, high-insulin treatment can enhances NA-induced
      contractility. This enhancement probably results from an upregulation of the
      expression of the mRNA for the alpha 1B- or alpha 1D-adrenergic receptor that is
      secondary to the hyperinsulinemia. The above effects may be made possible as a
      result of the increase in IGF-1 receptors and the decreased IGFBPs expressions
      that occur in the aorta in long-term insulin deficiency. In contrast, those
      insulin treatments can normalise the impaired endothelium-dependent relaxation,
      probably by inducing an overexpression of eNOS and VEGF. Furthermore, the
      expression of the IGF-1 receptor was higher in the aorta in insulin-treated
      diabetic than in untreated diabetes. This presumably increased the expression of
      VEGF mRNA, and the increased VEGF presumably upregulated eNOS, thereby resulting
      in an amelioration in the endothelial dysfunction otherwise seen in diabetic
      rats. The downside is that such a perturbation of the activity in the IGF-1
      system in diabetes could be a key event in the progress of arteriosclerosis and
      hypertension in syndromes involving hyperinsulinemia.

PMID- 14727519
TI  - [Changes in the contractility of the NIH3T3 fibroblast induced by the over
      expression of CPI-17].
AB  - The role of protein kinase C (PKC) in the regulation of contraction has been
      controversial. Recently, CPI-17, a PKC-potentiated inhibitor protein of PP1, has
      been cloned and shown to be specifically expressed in SMC. In this study, we over
      expressed CPI-17 and its mutants in NIH3T3 cells, which do not express CPI-17,
      and examined its effect on the contractile property. For the measurement of
      tension, NIH3T3 cells were collected by trypsinization, mixed with type I
      collagen and made into a ring preparation (reconstituted ring: RR). The isometric
      tension developments were measured using this RR and a force transducer. The
      application of phorbol dibutyrate (PDBu; 0.3 microM) to RR transfected by CPI-17
      induced a contraction that reached 2-3 times greater that the 10% FBS-induced
      contraction, while PDBu relaxed the RR transfected with vector alone (control) or
      CPI-17 mutants (T38A and T38E). The PDBu-induced contraction of the CPI-17
      transfected RR could be inhibited by 3 microM GF109203X (PKC inhibitor) but not
      by 3 microM Y27632 (rho kinase inhibitor). The application of PDBu during
      contraction induced by 1 microM bradykinin induced further contraction in CPI-17
      transfected RR, while it induced a complete relaxation in control RR. These
      results indicated that CPI-17 is a molecular switch that reverses the PKC
      mediated effect on contraction. The limited expression of CPI-17 to SMC may
      explain the previous observation that the effects of PKC stimulation were quite
      different in SMC from those of other cell types.

PMID- 14727520
TI  - [Mechanism of the intestinal dysmotility in the inflammatory bowel diseases:
      possible involvement of muscularis resident macrophages].
AB  - We evaluated the changes in interstitial cells of Cajal (ICCs) and myenteric
      nerve system in relation to the activity and number of muscularis resident
      macrophage at a level of myenteric nerve plexus in the Crohn's disease model
      treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the TNBS-treated rat
      colon, ICCs network and also myenteric nerve system were damaged or disappeared
      in the inflamed region. The number of ED2-immunoreactive resident macrophage
      significantly increased where the ICCs or myenteric nerve systems changed.
      Although resident macrophage appeared morphologically ramified in control
      intestine, TNBS-treatment changed it to round shape, possibly an indication of
      functionally activated state. In fact, the round shape of macrophage expressed
      marked MHC class II comparing ramified macrophage in control intestine.
      Physiological study indicated that the motility index, the amplitude and
      frequency of spontaneous contractions were significantly decreased in the TNBS
      induced colitis intestine. Moreover, the index of peristalsis observed in whole
      proximal colon tissue was inhibited by the treatment with TNBS. Electron
      microscopic analysis indicated that the contour of the myenteric ganglia became
      irregular in TNBS-treated rat colon, and numerous macrophages were observed
      around the ganglia. Similar results were obtained in the Hirschsprung's disease
      colitis model rats. In conclusion, the inhibition of spontaneous contractions and
      peristalsis in circular smooth muscle from TNBS-induced colitis rat colon may be
      attributable to the impairment of ICCs and myenteric nerve systems. Because of an
      indication of the macrophage activation and the close correlation between the
      degeneration and macrophage accumulation, it is suggested that the macrophages
      are involved in the degenerative pathology of intestinal motility.

PMID- 14727521
TI  - [Analysis of airway hyperresponsiveness using in vitro contraction model].
AB  - We have established an in vitro model of airway hyperresponsiveness, using bovine
      tracheal smooth muscle cells (BTSMC)-embedded collagen gel lattice. When the gel
      was pretreated with lysophosphatidic acid (LPA), which activates small G-protein
      RhoA, ATP- and high K+ solution-induced gel contraction was significantly
      augmented. This was not due to the modulation of Ca(2+)-mobilizing properties,
      since ATP- and high K(+)-induced Ca2+ transients were not different significantly
      between control and LPA-treated BTSMC. Y-27632, an inhibitor of Rho-kinase,
      suppressed the LPA-induced augmentation of gel contraction, whereas it did not
      inhibit the contraction of control gels. Theophylline (> or = 1 microM) reversed
      the LPA-induced augmentation of gel contraction, whereas it inhibited control gel
      contraction only with a very high concentration (100 microM) Theophylline
      suppressed the LPA-induced membrane translocation of RhoA, indicating that it
      prevented airway hyperresponsiveness by inhibiting RhoA. We conclude from these
      results that theophylline inhibits LPA-induced, RhoA/Rho-kinase-mediated
      hyperresponsiveness of tracheal smooth muscle cells.

PMID- 14727522
TI  - [beta-adrenoceptor subtypes involved in relaxations of guinea-pig
      gastrointestinal smooth muscles: distribution and signaling pathway of beta 3
      adrenoceptors].
AB  - The distribution and signaling pathway of beta 3-adrenoceptors involved in
      relaxations were examined in guinea-pig gastrointestinal smooth muscles. In
      esophagus, beta 1-adrenoceptors participate in isoprenaline-induced relaxations.
      However, both beta 2- and beta 3-adrenoceptors contribute to the relaxations in
      taenia caecum. In gastric fundus, duodenum, and ileum, beta 3-adrenoceptors were
      responsible for the relaxant responses. These results suggest that functional
      beta 3-adrenoceptors are present in four smooth muscles except esophagus. This
      was strongly supported by molecular analyses with RT-PCR, showing the expression
      of beta 3-adrenoceptor mRNA in the four tissues. beta 3-Adrenoceptor-mediated
      relaxations were unaffected by both an adenylyl cyclase inhibitor, SQ-22,536 (100
      microM), and a PKA inhibitor, H-89 (10 microM), in guinea-pig gastric fundus
      smooth muscle. Furthermore, in the presence of SQ-22,536 (100 microM), the
      stimulation of beta 3-adrenoceptors elicited relaxations without an elevation of
      cAMP, indicating the involvement of cAMP-independent mechanism(s). beta 3
      Adrenoceptor-mediated, cAMP-independent relaxations were significantly diminished
      by a Kv channel blocker, 4-aminopyridine (3 mM). These results indicate that beta
      3-adrenoceptors play a primary role in relaxations of guinea-pig gastrointestinal
      smooth muscles and 4-aminopyridine-sensitive Kv channels participate in cAMP
      independent smooth muscle relaxations in response to the activation of beta 3
      adrenoceptors.

PMID- 14727523
TI  - [Activation of smooth muscle myosin by the non-kinase role of myosin light chain
      kinase].
AB  - Myosin light chain kinase (MLCK) is a regulatory protein for smooth muscle
      contraction, which acts by phosphorylating 20-kDa myosin light chain (MLLC20) to
      activate the myosin ATPase activity. Although this mode of action is well
      established, there are numberous reports of smooth muscle contraction that is not
      associated with MLC20 phosphorylation. The kinase activity for the
      phosphorylation is localized at the central part of MLCK, which is also furnished
      with actin-binding activity at its N terminal and myosin-binding activity at its
      C terminal. I will overview as to how such multifunctional properties of MLCK
      modify the actin-myosin interaction and presents our observations that the
      phosphorylation is not obligatory in induction of smooth muscle contraction and
      migration.

PMID- 14727524
TI  - [Reserpine-induced supersensitivity and alpha 1-adrenoceptor subtypes].
AB  - Supersensitivity is one of classical and pharmacological phenomena, and may be
      caused by a variety of procedures, including surgical and chemical denervation
      and chronic treatment with antagonists. We examined reserpine-induced chemical
      denervation supersensitivity with special reference to arterial alpha 1
      adrenoceptor (alpha 1-AR) subtypes. Chronic treatment with reserpine for 2 weeks
      produced supersensitivity in the contractile response to phenylephrine of
      isolated rat tail artery, resulting a leftward shift of concentration-response
      curve (10 fold shift at EC50 value). This supersensitivity in reserpine-treated
      artery was selectively inhibited by BMY7378 (alpha 1D-AR selective antagonist)
      but not by KMD-3213 (alpha 1A-AR selective antagonist). On the other hand, the
      response to phenylephrine in reserpine-untreated artery was inhibited by KMD-3213
      but not by BMY7378. Tissue segment binding study with 3H-prazosin revealed that
      high affinity binding sites for BMY7378 were detected with a proportion of 32% in
      reserpine-treated tail artery but absent in untreated artery, although total
      density of alpha 1-ARs was not changed by reserpine-treatment. The present
      results strongly suggest that reserpine-induced supersensitivity of rat tail
      artery is caused by a selective induction of alpha 1D-AR subtype.

PMID- 14727525
TI  - [Functional difference of prokinetics depending on subtypes and localization of
      receptor in alimentary tract].
AB  - Interaction of function and localization of receptors, especially the 5
      hydroxytryptamine4 (5-HT4) receptor was examined in relation to the motility of
      gastrointestinal tract. The responses mediated by stimulation of 5-HT4 receptor
      appear to differ with different localization of receptor. The 5-HT4 receptor
      mediated acceleration of acetylcholine (ACh) release in the preparations isolated
      from gastric antrum and corpus, but not fundus, of guinea pig corresponded to the
      presence of 5-HT4 receptor in the myenteric plexus. The 5-HT4 receptor-mediated
      response was predominant in the 5-HT-induced acceleration of motility associated
      with ACh release in the intestine of the whole body of dogs, and the 5-HT4
      receptor was localized on the myenteric plexus of dog intestine. Local
      administration of GABA into intestinal marginal artery reduced the motility
      associated with ACh release in the intestine of whole body of dogs, and thus
      response via the inhibitory GABAB receptor was more predominant than that via
      excitatory GABAA receptor. The GABAB receptor is the first G protein-coupled
      receptor discovered to form heterodimers, consisted of GABAB1 and GABAB2. There
      are isoforms of GABAB1, from GABAB1(a) to GABAB1(g), and therefore the function
      and localization of the GABAB receptor may vary with the different isoforms of
      GABAB1.

PMID- 14727526
TI  - [Regulation of the drug-sensitivity of anion channels via phosphorylation].
AB  - Chloride channels in mammalian cell membranes play an important role in cell
      homeostasis. The Cl- channels that have been identified as molecular entities are
      CFTR, CLC, CLCA, etc. We focused on two types of these channels and investigated
      their modulatory mechanism. (i) Endothelin-activated oscillatory Cl- currents in
      the smooth muscle cells of the microvasculature have been shown to be
      attributable to Ca2+ released from intracellular stores. These currents were
      inhibited by protein kinase (PK) A activation by agents such as forskolin and
      prostacyclin. Since overexpressed CLCA Cl- channels newly cloned from rats were
      directly suppressed by forskolin Ca(2+)-activated Cl- channels are likely to be
      modulated by PKA-mediated phosphorylation in an inhibitory manner. (ii) A CFTR
      isoform is known to be expressed in myocardial cells and to participate in the
      regulation of cell excitability. In Xenopus oocytes expressing the isoform, the
      Cl- current was found to be activated by PKA-mediated phosphorylation. In
      experiments using inhibitors of phosphorylation and dephosphorylation, the PKA
      mediated effect was shown to be regulated by the phosphorylated states modulated
      by PKC endogenously. These results suggest that the Cl- channel activity may be
      influenced by the basal phosphorylated states modulated by different types of
      kinases in addition to the main regulatory pathway.

PMID- 14727527
TI  - [Role of PGI2 in ectopic bone formation of spinal ligaments].
AB  - Ossification of the posterior longitudinal ligament (OPLL) is characterized by
      ectopic bone formation in the spinal ligaments. It has been suggested some role
      of mechanical stress in the progression of OPLL. Differential display RT-PCR was
      carried out to identify the genes participating in OPLL. A cDNA fragment
      corresponding to PGI2 synthase was highly expressed in OPLL cells compared to non
      OPLL cells. To examine the effect of mechanical stress on the PGI2 synthase
      expression, cells were subjected to cyclic stretch and PGI2 synthase expression
      was assessed by quantitative RT-PCR. Cyclic stretch induced a time-dependent
      increase in PGI2 synthase in OPLL cells but not in non-OPLL cells. The increase
      in PGI2 synthase was diminished by SQ22536, a potent adenylate cyclase inhibitor.
      Cyclic stretch also induced PGI2 production. Beraprost and dibutyryl cAMP
      increased the mRNA expression of alkaline phosphatase (ALP) as a marker for
      osteogenic differentiation in OPLL cells, whereas no change was observed in non
      OPLL cells. Beraprost- and stretch-induced increases in ALP expressions were
      inhibited by SQ22536. These data suggest that PGI2 synthase activated by
      mechanical stress plays a key role in the progression of OPLL, at least in part
      through the osteogenic differentiation in spinal ligament cells via the PGI2/cAMP
      system.

PMID- 14727528
TI  - [New target for the inhibitors of gastric acid secretion. Inhibition of myosin
      and actin activities via the apical membrane of parietal cells in dogs].
AB  - This report aims to highlight drugs that are able to inhibit parietal cells from
      the luminal side, resulting in suppressed gastric acid secretion. Histamine 2HCl
      was i.v. given continuously to obtain a submaximal stimulation of gastric acid
      secretion. Wortmannin and ME 3407 (a myosin light chain kinase inhibitor) and
      cytocharasin D (actin polymerizing inhibitor) were locally applied to denervated
      gastric pouches prepared in dogs for 5 to 30 min. Each drug, administered 0.5 hr
      before or 1 hr after histamine infusion was commenced, significantly inhibited
      stimulated-gastric acid secretion in a time-dependent manner. The antisecretory
      effect persisted for more than 24 hrs in the case of Wortmannin and 9 hr in the
      case of ME 3407 at a dosage 1 and 3 mg/pouch for 30 min, respectively. ME 2407,
      however, had no antisecretory effect when i.v. administered after histamine
      infusion, or orally administered before histamine infusion. Such results strongly
      suggest that the apical membrane of parietal cells possesses a ME 4307,
      Wortmannin and cytocharasin D sensitive portion similar to the basolateral
      membrane that usually mediates gastric acid secretion. The apical membrane
      represents an intriguing target for developing new antisecretory drugs, as well
      as for elucidating the functional features of parietal cells.

PMID- 14727529
TI  - [A potential of positron emission tomography in the drug development of non
      sedative antihistamines].
AB  - Histamine H1 receptor antagonists, or antihistamines, are very effective for
      treatment of various allergic disorders such as seasonal rhinitis and urticaria.
      Sometimes antihistamines induce sedative CNS side effects that might result in
      dangerous traffic accidents. That is why a lack of sedation is important for
      development of new antihistamines. It is clear that all antihistamines have a
      potential to produce subjective (sleepiness, fatigue etc.) and objective sedation
      (impaired performance), dependent on the histaminergic mechanisms involved in the
      control of arousal. We have proposed the usefulness of H1 receptor occupancy
      measurement with Positron Emission Tomography (PET) using 11C-doxepin as a
      tracer. The PET measurement is currently included as one of the three major
      factors defined by the international Consensus Group on New Generation
      Antihistamines (CONGA) for evaluation of antihistamines: 1) incidence of
      subjective sleepiness, 2) objective and psychomotor functions, and 3) PET
      measurement of H1 receptor occupancy. Merit of PET measurement is that we can
      directly calculate the receptor occupancy for each separate drug while the former
      two should be discussed based on the difference between placebo and active
      placebo. PET will be used more actively in the development of various new drugs
      in future.

PMID- 14727530
TI  - [Candidate genes or compounds for therapeutic tools against methamphetamine
      and/or morphine-induced dependence].
AB  - Drug dependence is one of most severe problems in all over the world, however,
      the mechanisms and related-genes have not been completely revealed. Here we would
      like to introduce tumor necrosis factor-alpha (TNF-alpha). Repeated treatment
      with methamphetamine induced an increase in TNF-alpha mRNA in the some brain
      regions. Exogenous TNF-alpha blocked the methamphetamine rewarding. TNF-alpha
      plays a neuroprotective role in methamphetamine drug dependence. These results
      suggest that TNF-alpha is one of key proteins. TNF-alpha itself might not be
      therapeutic tools, since it has immunological actions in physical conditions.
      Therefore, next, we found a stimulator, Leu-Ile, which enhances TNF-alpha
      synthesis in cultured neurons. Leu-Ile protected blocked the methamphetamine
      induced rewarding effects. These results suggest that a stimulator of TNF-alpha
      synthesis may be one of therapeutic tools against drug dependence.

PMID- 14727531
TI  - [Thymidine phosphorylase inhibits apoptosis induced by anticancer agents].
AB  - An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine
      phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and
      confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a
      degradation product of thymidine generated by TP enzymatic activity, partially
      prevented hypoxia-induced apoptosis. TP was expressed at higher levels in tumor
      tissuses compared to the adjacent non-neoplastic tissues in a variety of human
      carcinomas. High expression of TP is associated with an unfavorable prognosis. To
      investigate the effect of TP on cisplatin-induced apoptosis, human leukemia
      Jurkat cells were transfected wild-type or mutant (L148R) TP cDNA. TP inhibits a
      number of steps in the cisplatin-induced apoptotic pathway, activation of caspase
      3, 9 and mitochondrial cytochrome c release. These findings suggest a mechanism
      by which TP confers the resistance to apoptosis by cisplatin. Moreover, mutant TP
      that has no enzymatic activity also suppressed cisplatin-induced apoptosis. These
      findings indicate that TP has cytoprotective functions against cytotoxic agents
      which are independent of its enzymatic activity.

PMID- 14727532
TI  - [Neuropathology of polyglutamine diseases].

PMID- 14727533
TI  - [Higher brain dysfunction after traumatic brain injury: its characteristics and
      pitfalls in diagnosis].

PMID- 14727534
TI  - [Vascular endothelial growth factor expression in the rat dural arteriovenous
      fistula model].
AB  - Although various mechanisms of the development of dural arteriovenous fistula
      (DAVF) have been proposed, the pathogenesis of these lesions are still unclear.
      Recent experimental evidence suggested a role of angiogenic growth factors in the
      genesis of vascular malformations of the central nervous system. To further
      investigate the pathogenesis of DAVF, we examined the expression of the
      angiogenic growth factor, vascular endothelial growth factor (VEGF), in rat DAVF
      model. MATERIAL AND METHODS: Male Wistar rats (weighting 280 to 300 g, n = 40)
      were used. Each rat was mounted on a stereotaxic frame under general anesthesia.
      DAVF model (Spetzler et al.) was made by common carotid artery-external jugular
      vein anastomosis, bipolar coagulation of the vein draining the transverse sinus,
      and superior sagittal sinus thrombosis (SSS). SSS was thrombosed by a hemostatic
      agent through 16-gauge needle. Venous hypertension was induced in 30 rats, which
      were divided into two experimental groups; (1) immunohistological study group (n
      = 15) and (2) angiography group (n = 15). Immunohistological analysis was
      performed by VEGF antibody 1 week after, and angiography was done 90 days after
      the surgery. Developing of angiographical DAVF was observed with the magnifying X
      ray camera. Each 5 rats served as sham-operated controls, which received a
      similar surgery without induction of venous hypertension. RESULTS: VEGF
      expression and DAVF were not observed in sham group. In immunohistological study
      group, VEGF expression in the endothelium and the connective tissues of the dura
      mater in the five rats (33%) and in the neurons in the eleven rats (73%) of the
      cerebral cortex and the basal ganglia were identified. In angiography group, DAVF
      formed in 6 among 15 rats (40%). CONCLUSION: The findings of this study provide
      the first experimental evidence that angiogenic growth factors VEGF may
      participate in the genesis of DAVF. These results suggest a novel strategy for
      the management and prevention of DAVF and related disorders.

PMID- 14727535
TI  - [Clinical significance of natriuretic peptides in patients with aneurysmal
      subarachnoid hemorrhage].
AB  - Hyponatremia and hypovolemia following aneurysmal subarachnoid hemorrhage (SAH)
      might be speculated by exaggerated secretion of natriuretic peptides and resulted
      ischemic sequela caused by cerebral vasospasm. We measured serum concentration of
      natriuretic peptides and investigated their influence on post-SAH hyponatremia.
      Among 49 patients of SAH, their plasma concentration of the natriuretic peptides
      (atrial natriuretic peptide: ANP and brain natriuretic peptide: BNP) were
      measured at the day of ictus and 7th day of SAH. The correlation between
      concentration of natriuretic peptides and location of aneurysm, severity of SAH,
      incidence of hyponatremia and symptomatic vasospasm were elucidated. The plasma
      concentration of ANP did not alter on admission and 7th day post SAH, whereas
      that of BNP increased in the patients with moribund SAH and those with ruptured A
      com aneurysm. The initial increase of BNP following SAH could be attributed to
      direct damage of SAH on the hypothalamus. Hyponatremia and symptomatic vasospasm
      tended to occur in the patients who had persistent increase of plasma BNP
      concentration during one week post SAH. Therapeutic intervention to maintain
      normonatremia by fluid-management decreased occurrence of symptomatic vasospasm,
      even though patients with increased plasma BNP concentration. It might be
      concluded that increased secretion of BNP following SAH is caused by direct
      effect to the hypothalamus and prolonged hyper secretion of BNP resulted
      hyponatremia, hypovolemia and exaggerated symptomatic vasospasm.

PMID- 14727536
TI  - [A case of Guillain-Barre syndrome starting from severe upper back pain].
AB  - Examination of a 58-year-old woman who had developed severe upper back pain
      showed left peripheral type of facial nerve palsy, sensory disturbance of limbs
      and body trunk (Th7-9), cerebellar ataxia and generalized hyporeflexia. Upper
      back pain increased at night and was resistant to NSAIDs, antianxiety agents,
      opioids, and corticosteroids. Concentrations of serum CK and cerebrospinal fluid
      total protein were elevated. Electromyography (EMG) of perivertebral muscles (Th7
      10) showed reduced recruitment and polyphasic potential. Several days later, our
      patient developed weakness of limbs and respiratory failure, and required
      mechanical ventilation. From these findings, we diagnosed her as having Guillain
      Barre syndrome (GBS) and began treatment with intravenous immunoglobulin therapy.
      All symptoms including upper back pain improved gradually, and she had recovered
      almost completely by the 40th hospitalization day. Pain, especially lower back
      and leg pain, have attracted attention as common symptoms in GBS. However, only
      one GBS patient with initial severe upper back pain has been reported. Although
      the precise mechanism of pain in GBS remains unclear, EMG findings lead us to
      surmise our patient's pain originated from the nerve roots. Limb and back pain
      should therefore be taken into account for the diagnosis and treatment of GBS
      patients.

PMID- 14727537
TI  - [Spontaneous remission of acromegaly after meningitis: a case report].
AB  - There have been several reports describing the cases of acromegaly, which show
      reduction in size of tumor in due to pituitary apoplexy or lymphocytic
      hypophysitis. We have encountered a patient of acromegaly, who developed
      panhypopituitarism after suffering from meningitis and showed the reduction of
      tumor in size. The results of imaging examination suggested the presence of
      pituitary apoplexy and lymphocytic hypophysitis. The patient was a 27-year-old
      woman, who visited a local physician with complains of headache and fever. After
      performing lumbar puncture, she was diagnosed as viral meningitis, and
      conservative therapy was initiated. The results of biochemical test of blood
      revealed hyponatremia. Because facial appearance of the patient was similar to
      that of acromegaly, endocrine dysfunction was suspected. The result of pituitary
      hormone tests showed high levels of growth hormone (GH) and somatomedin C (IGF-1)
      and low levels of the other hormones. At the same time, sign of diabetes
      insipidus was noted, and the patient was referred to our hospital. In the
      examination at the admission, GH and IGF-1 showed the trends to decrease, and the
      reduction in size of tumor was also detected. From the results of imaging
      examination, pituitary apoplexy and lymphocytic hypophysitis were suspected.
      Operation was performed, and pathological examination revealed inflammation of
      pituitary adenoma.

PMID- 14727538
TI  - [Two cases of generalized tetanus presenting with dysphagia as an initial
      symptom].
AB  - We describe two patients with generalized tetanus, a 60-year-old man and a 76
      year-old woman, presenting with dysphagia as an initial symptom of the disease.
      Eighty percent of patients with generalized tetanus manifest dysphagia on
      admission to a hospital. However, dysphagia is rare as an initial symptom. Both
      our patients had dysphagia as their initial symptom, followed by neck stiffness
      and trismus. We made a diagnosis of generalized tetanus based on these
      neurological findings in the absence of an apparent episode of trauma. After the
      administration of tetanus immunoglobulin on admission, they recovered without
      exhibiting generalized convulsion, autonomic storm, or any other serious
      complications. The vaccination of tetanus toxoid cannot maintain sufficient
      antibody titers more than ten years. Therefore, elderly people are considered
      susceptible to tetanus. We suggest that tetanus should be considered in the
      differential diagnosis of dysphagia particularly in elderly patients. We also
      suggest that treatment of tetanus should be initiated immediately, because
      tetanus still has a high mortality rate at present.

PMID- 14727539
TI  - [Angiographic features of anoxic encephalopathy in the acute phase: a case
      report].
AB  - We present an angiographic feature of anoxic encephalopathy in the acute phase. A
      68-year-old woman suddenly presented with deep coma. Examinations of her blood
      and electrocardiography did not reveal the origin of consciousness disturbance,
      and computed tomographic (CT) scans demonstrated no significant findings. We
      immediately performed cerebral angiography because we suspected brain stem
      infarction. A 3-vessel study (bilateral carotid and left vertebral angiography)
      revealed remarkable delays in cerebral circulation time or arteriovenous
      circulation time, although it did not show occlusion of cerebral vessels. The
      follow-up brain magnetic resonance (MR) images revealed anoxic encephalopathy,
      which might be derived from transient cardiac arrest. The patient has been in a
      vegetative state for one year. Although many reports have described CT scans and
      MR images of anoxic encephalopathy in the acute or subacute phases, there have
      been no reports about the angiographic features. We found remarkable delays in
      cerebral circulation time in the acute phase of anoxic encephalopathy, which was
      considered to be caused by cytotoxic edema from severe hypoxia or ischemia.

PMID- 14727540
TI  - [Usefulness of carotid duplex ultrasonography in a patient with moyamoya
      disease].
AB  - The patient is a 35-year-old man who had a medical history of epilepsy in
      childhood. He came to our hospital because of transient disturbance of
      consciousness and left hemiplegia just after evacuation. At first, we thought
      that he had epilepsy with Todd's palsy. But we had to do a differential diagnosis
      for a transient ischemic attack such as paradoxical embolism, because his
      symptoms occurred just after evacuation. An electroencephalogram and brain
      computerized tomography were immediately performed, but no abnormality was
      detected. Hematologic studies were normal, and no deep vein thrombosis was
      detected in the veins of the lower extremities by duplex ultrasonography Doppler.
      But carotid duplex ultrasonography showed an increase in end-diastolic flow
      velocity and a decrease in vascular resistance in both external carotid arteries.
      These findings indicated that there was arteriovenous malformation such as
      moyamoya disease. Brain magnetic resonance imaging showed spotty high signal
      lesions in the subcortical areas on a fluid-attenuated inversion-recovery(FLAIR)
      image, and the middle cerebral artery was not visualized on magnetic resonance
      angiography (MRA). Cerebral angiography demonstrated moyamoya vessels in the
      brain and collateral circulation from the external carotid artery. Therefore, we
      diagnosed him as having moyamoya disease. Duplex ultrasonography of the common
      and, internal carotid, and vertebral arteries is a widely-used technique.
      Recently, cerebral angiography, MRA and transcranial Doppler have been applied to
      detect intracranial vascular malformation. But these results suggested that
      moyamoya disease could be detected by means of carotid duplex ultrasonography.
      Finally, we considered that carotid duplex ultrasonography was not only a
      noninvasive screening method but also a useful for the diagnosis of moyamoya
      disease.

PMID- 14727541
TI  - [A case of traumatic sinus pericranii communicating to superior sagittal sinus
      demonstrated by MRI with Gd-DTPA administration].

PMID- 14727542
TI  - [Proton magnetic resonance spectroscopy of cavernous sinus hemangioma:
      possibility for differentiated diagnosis from meningioma].

PMID- 14727543
TI  - [An autopsy case with sequela of encephalopathy and fibromuscular dysplasia of
      the renal artery].

PMID- 14727544
TI  - [Clinical aspect of diffuse alveolar hemorrhage syndrome].
AB  - Thirteen cases of diffuse alveolar hemorrhage (DAH) were encountered in our
      Hospital between January 1996 and October 2001. Eight patients were men and five
      were women, their mean age being 59.5 +/- 19.2 years (range, 18-88 years). Three
      patients had systemic lupus erythematosus (SLE), three (23%) had polyarteritis
      nodosa (including microscopic PN), one (7.7%) had allergic granulomatous angitis,
      one (7.7%) had Goodpasture syndrome, one (7.7%) had MPO-ANCA-associated
      vasculitis, one (7.7%) had Behcet's disease, one (7.7%) had chronic heart failure
      caused by mitral stenosis, one (7.7%) had chronic renal failure (etiology
      unknown), and the last had no particular disorder. Nine episodes (69%) had
      occurred as complications of primary diseases, four (31%) as the first symptoms
      of underlying diseases. Prognosis was poor in the former cases but in the latter,
      the prognosis was relatively favorable.

PMID- 14727545
TI  - [Clinical usefulness of serum pyridinoline cross-linked carboxyterminal
      telopeptide of type I collagen (ICTP) for diagnosis of bone metastasis in
      patients with primary lung cancer].
AB  - Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP)
      is a metabolite of type I collagen representing more than 90% of organic
      substances in bone and expected to be one of the markers reflecting bone
      resorption. We measured ICTP to evaluate its clinical usefulness for diagnosis of
      bone metastasis from primary lung cancer by comparing serum alkaline phosphatase
      (ALP), a bone formation marker, which was simultaneously measured. In addition,
      using the receiver operating characteristic (ROC) curve, we calculated the cut
      off value of ICTP from which the diagnostic accuracy serves as best. The subjects
      were 87 patients with primary lung cancer including 21 patients with bone
      metastasis. ICTP was significantly higher in patients with bone metastasis than
      in the group without bone metastasis. On the other hand, in the serum ALP there
      was no significant difference between the two group. The result suggested that
      measurement of serum ICTP is worthwhile as a diagnosis method of bone metastasis
      from lung cancer. The calculated cut-off value was 6.4 ng/ml, higher than the 4.5
      ng/ml indicated by the appending document which was from patients with lung,
      breast and prostate cancer. It is possible that the reason for the style of bone
      metastasis from lung cancer is mainly a osteolytic process.

PMID- 14727546
TI  - [Effect of lung volume reduction surgery (LVRS) on nutritional status in patients
      with COPD].
AB  - The beneficial effects of lung volume reduction surgery (LVRS) on patients with
      severe chronic obstructive pulmonary disease (COPD) on pulmonary function and
      exercise performance has been established. However, the impact on nutritional
      status and prognosis has not been demonstrated. In the present study, we
      investigated the changes in nutritional status in COPD patients undergoing
      bilateral thoracoscopic LVRS and also analyzed the relationship between
      nutritional status and postoperative complications and prognosis. After LVRS,
      body weight, fat-free mass (FFM) and caloric intake were significantly increased.
      Increase in FFM correlated significantly with improvement in exercise
      performance. In underweight patients before LVRS, the incidence of post-operative
      complications was significantly higher than in normal-weight patients, and a
      patient who was moderately-to-severely underweight (% ideal body weight < 80%)
      had a significantly poor prognosis. These findings suggest that improvement of
      nutritional status after LVRS contributes to improvement in exercise performance,
      and that preoperative nutritional status has a significant impact on
      postoperative morbidity and mortality. From our data, we concluded that
      preoperative nutritional assessment is an important part of the preoperative
      evaluation of LVRS, and that LVRS provides nutritional benefits for underweight
      patients with severe COPD.

PMID- 14727547
TI  - [Clinical features of Q fever pneumonia].
AB  - We report four cases of Q fever pneumonia diagnosed using PanBio Coxilla burnetii
      ELISA. The patients, a 21-year-old woman, a 53-year-old man, a 74-year-old man
      and a 87-year-old man, were among 284 with community-acquired pneumonia who were
      treated as inpatients from March 2001 till March 2003. The frequency of Q fever
      pneumonia in community-acquired pneumonia was 1.4%. The 21-year-old woman was a
      typical case of Q fever pneumonia, since her clinical features showed 1. the
      breeding of cats, 2. development from a fever and non-productive caught in March,
      3. multiple soft consolidations in the chest radiograph, 4. normal WBC count, 5.
      cure by administration of clarithromycin. The pneumonias of the other 3 cases
      were considered to be mixed infections, with bacteria such as Streptococcus
      pneumoniae and Haemophilus influenzae. Their clinical features were 1. elderly
      male patients with underlying diseases, 2. development from fever and cough with
      purulent sputum in winter, 3. coarse crackle on auscultation, 4. consolidation
      with pleural effusion in chest radiograph, 5. leukocytosis, elevation of BUN,
      hyponatremia, 6. a few cases with unfavorable prognoses despite medication with
      carbapenem and minocycline. These findings suggested that two types of pneumonia
      exist; one with the usual features of atypical pneumonia, and the other
      presenting the clinical features of bacterial pneumonia of the elderly due to a
      mixed infection including C. burnetti.

PMID- 14727548
TI  - [A case of pulmonary cryptococcosis with multiple nodular shadows under treatment
      of bronchiolitis obliterans with organizing pneumonia (BOOP)].
AB  - A 66 year-old man was introduced to our hospital because of multiple infiltrative
      pulmonary shadows on February, 2001. We diagnosed bronchiolitis obliterans with
      organizing pneumonia (BOOP) from the clinical and bronchoalveolar lavage fluid
      (BALF) findings, and initiated oral steroid therapy. Since the abnormal chest
      shadows disappeared, the dose of steroid was decreased and maintained at 10
      mg/day. In August 2001, multiple infiltrative shadows returned, and we therefore
      increased the steroid dose to 30 mg/day. The expanding infiltrative shadows were
      then joined by new multiple nodular shadows. The bronchioalveolar lavage fluid
      revealed small bodies of cryptococcus species. A positive result for anti
      cryptococcus antigen was also obtained from the serum. We then diagnosed
      pulmonary cryptococcosis without meningitis. Therapy was started with anti
      mycotic agents including amphotericin-B, flucytosine and fluconazole, which
      proved successful. This case of opportunistic cryptococcus infection in an
      immunocompromized patient, which responded to anti-mycotic therapy, is reported.

PMID- 14727549
TI  - [A case of loxoprofen sodium-induced bronchiolitis obliterans organizing
      pneumonia (BOOP)].
AB  - A 78-year-old man was referred to our department because of an abnormal shadow on
      the chest radiograph and liver dysfunction after lung resection for lung cancer.
      Following the operation, loxoprofen sodium was administered to control his chest
      pain. A chest radiograph on admission showed airspace consolidation in the right
      lower lung field. In addition, leukocytosis and elevation of CRP were observed.
      Although piperacillin sodium was given to him, airspace consolidation on a chest
      radiograph was increased. A bronchoalveolar lavage fluid study showed that total
      cell counts and proportion of lymphocytes were increased, and the CD4/CD8 ratio
      was 1.77. A transbronchial lung biopsy specimen revealed organizing pneumonia
      with Masson bodies. Furthermore, a lymphocyte stimulation test for loxoprofen
      sodium was positive. From the clinical course, laboratory data and pathologic
      findings, we considered this case to be loxoprofen sodium-induced BOOP.
      Withdrawal of loxoprofen sodium and treatment with corticosteroid resulted in
      marked improvement of the clinical findings. Although a rare occurrence, it is
      important to recognize that BOOP can be caused by loxoprofen sodium.

PMID- 14727550
TI  - [A case of small-cell lung cancer during treatment for active pulmonary
      tuberculosis after surgery for non-small-cell lung cancer].
AB  - A 76-year-old man taking anti-tuberculous drugs for active pulmonary tuberculosis
      was admitted to our hospital requiring further examination of a pulmonary mass in
      the left upper lobe. He had had right lower lobectomy and partial middle
      lobectomy for non-small-cell lung cancer two years before admission.
      Retrospectively, the left upper lobe mass had been gradually growing for about 2
      months. We performed a transbronchial lung biopsy of the pulmonary mass, and
      diagnosed small-cell lung cancer. This report describes a rare case of small-cell
      lung cancer appearing during treatment for active pulmonary tuberculosis after
      non-small-cell lung cancer surgery.

PMID- 14727551
TI  - [A case of acute hypersensitivity pneumonitis caused by contact with budgerigars
      (bird-breeder's lung)].
AB  - A 58-year-old woman was admitted to our hospital for repeated episodes of dry
      cough, low-grade fever, and gradual development of dyspnea on exertion. Chest
      computed tomography showed diffuse ground-glass opacities in both lung fields.
      Bronchoalveolar lavage fluid (BALF) showed an increased number of lymphocytes,
      and transbronchial lung biopsy revealed alveolitis and epithelioid cell
      granuloma. The acute onset and the patient's living environment suggested summer
      type hypersensitivity pneumonitis. However, anti-Trichosporon antibody was
      negative and a definitive diagnosis could not be made. The patient's condition
      improved with corticosteroid treatment and, after discharge from the hospital,
      she moved to a new home. The following year, however, her symptoms returned, and
      she was readmitted to our hospital. Recurrence of the disease despite the change
      in environment ruled out summer-type hypersensitivity pneumonitis. Given the
      patient's history of budgerigar breeding five years earlier, bird breeder's lung
      was suspected. Anti-bird excreta antibody found in the patient's serum and BALF,
      along with a positive lymphocyte stimulation test against pigeon serum, strongly
      suggested an acute onset of bird breeder's lung. We report a rare case of acute
      bird breeder's lung with radiologic findings of ground-glass opacities, a one
      year disease-free period and an acute relapse.

PMID- 14727552
TI  - [A case report of intralobar sequestration with a Mycobacterium tuberculosis
      infection limited to the sequestrated lung].
AB  - A 22-year-old woman was referred to our hospital suffering from repeated
      exacerbation of infiltrates confined to the medial portion of the right lower
      lung lobe, suggestive of pulmonary sequestration. Angiography revealed an
      anomalous vessel originating from the left side of the descending aorta, flowing
      behind it into the right lower lobe, the blood being returned to the pulmonary
      veins. A resection of the right lower lobe was conducted via thoracotomy.
      However, since there was no clear normal lung-pleura interface, this was
      classified as Pryce II type intralobar sequestration. Epithelioid granulomas with
      associated caseation necrosis confined to the sequestrated lung were confirmed by
      a polymerase chain reaction as Mycobacterium tuberculosis. Following oral
      antituberculosis drug administration, the patient recovered uneventfully.
      Superimposition of tuberculosis confined to a sequestrated lung portion is
      extremely rare. The presence of the aberrant artery led us to conclude that the
      intralobar sequestration must have been congenital.

PMID- 14727553
TI  - [A case of malignant lymphoma associated with diffuse pulmonary involvement
      successfully treated with rituximab].
AB  - A 66-year-old man was admitted to our hospital with a chief complaint of fever.
      Histopathological examination of the inguinal lymph nodes revealed follicular B
      cell non-Hodgkin's lymphoma (NHL). In spite of 9 cycles of chemotherapy
      (CHOP/COP), progression of the disease was seen. Fever and dyspnea developed. The
      chest radiograph revealed diffuse pulmonary infiltrates. Transbronchial biopsy
      revealed pulmonary involvement of diffuse B-cell lymphoma. The tumor cells showed
      positive staining for CD20. Salvage chemotherapy (ESHAP, EPOCH) was not
      effective. We decided to perform mono-immunotherapy with the monoclonal CD20
      antibody rituximab. One month later, the patient was in almost complete remission
      without adverse events. It is suggested that rituximab may be effective for
      refractory NHL with pulmonary involvement.

PMID- 14727554
TI  - [A case of pleural effusion associated with allergic bronchopulmonary
      aspergillosis during a relapse of the disease].
AB  - A 61-year-old man with history of bronchial asthma since childhood was admitted
      to our hospital for examination of eosinophilia and of lung infiltration seen in
      the chest radiograph. Allergic bronchopulmonary aspergillosis (ABPA) was
      diagnosed on the basis of the following findings: elevated serum IgE level,
      positive immediate skin reaction to Aspergillus antigen, the presence of
      precipitating antibodies against Aspergillus antigen, and central bronchiectasis.
      Oral prednisolone administration (30 mg daily) was started. During the course of
      reducing the prednisolone dose by up to 5 mg per day, pleural effusion appeared
      in the right lung. It was speculated that this eosinophilic exudative effusion
      was associated with a relapse of ABPA. After treatment with the dose of
      prednisolone increased to 20 mg per day and with oral itraconazole, the pleural
      effusion disappeared. We report a rare case of pleural effusion associated with
      ABPB on relapse.

PMID- 14727555
TI  - [A case of catamenial pneumothorax due to diaphragmatic endometriosis confirmed
      by video-assisted thoracoscopic surgery].
AB  - We describe a case of catamenial pneumothorax caused by diaphragmatic
      endometriosis and histologically confirmed thoracoscopically. The patient was a
      33-year-old woman who had had recurrent right chest pain starting on the day
      preceding each menstruation since she was 26 years of age. In June 2001, at the
      age of 33, she felt right chest pain and developed dyspnea, and so came to our
      hospital. Chest radiography showed bilateral pneumothorax. Timely thoracoscopy
      revealed the characteristic appearances of catamenial pneumothorax such as a
      blueberry spot on the central tendon of the right diaphragm and a purplish-red
      locus in the right apex. Histopathological examination further confirmed the
      presence of endometrial tissue on the diaphragm as well as in the lesion of the
      right lung. Despite resection of the endometrial tissues from the right
      hemidiaphragm and the lung under thoracoscopy, right pneumothorax recurred after
      one month. Since then, the patient's condition has been well controlled by
      therapy with gonadotropin releasing hormone, with no recurrence of catamenial
      pneumothorax.

PMID- 14727556
TI  - [Pancreatic metastasis from lung cancer: report of an autopsy case].
AB  - A 69 year-old man with abnormal lung shadows in the right lung field was admitted
      to our hospital. A chest computed tomography (CT) scan showed a lung tumor with
      hilar and mediastinal lymph node swelling. A CT scan of the abdomen demonstrated
      a solitary pancreatic head tumor with a diameter of 3 cm. Pathological
      examination of a transbronchial biopsy specimen revealed squamous cell carcinoma
      (SCC) of the lung. Since obstructive jaundice had progressed rapidly, the patient
      received endoscopic nasobiliary drainage (ENBD) and stent-drainage therapy prior
      to chemotherapy using gemcitabine. However, he died 4 months later of respiratory
      failure and systemic candidiasis associated with progression of the cancer. An
      autopsy was performed, and microscopic and immunohistochemical examination
      revealed that the pancreatic tumor was a metastasis from lung cancer. To our
      knowledge, obstructive jaundice due to pancreatic metastasis from lung SCC,
      especially that preceding the advent of a clinical manifestation of primary lung
      cancer, has rarely been reported.

PMID- 14727557
TI  - [A case of primary pulmonary MALT lymphoma as a nodular shadow on CT scan, and
      relapsed with diffuse micronodular shadows after surgical resection at 7 years
      ago].
AB  - A 76-year-old man without symptoms was admitted to our hospital for investigation
      of an abnormal chest shadow in 1994. His chest radiograph showed a nodular shadow
      in the lingual lobe. Segmentectomy was performed and the histological diagnosis
      was MALT (mucosa-associated lymphoid tissue) lymphoma. In June 2001, there were
      no abnormal shadows on the chest radiograph or in 10 mm slice CT. However, high
      resolution CT with 2-mm slice thickness revealed diffuse micronodular shadows in
      both lungs. A relapse of MALT lymphoma was diagnosed by immunohistochemical
      analysis of tissue specimens obtained by transbronchial lung biopsy. It was
      observed that the patterns of radiological findings in primary pulmonary MALT
      lymphoma cases may differ between the initial state and a relapse.

PMID- 14727558
TI  - [Primary new daily persistent headache (NDPH): clinical characteristics of forty
      three cases in Japan].
AB  - Although the primary chronic daily headache is subdivided into chronic migraine,
      chronic tension-type headache, hemicrania continua, and new daily persistent
      headache (NDPH), the characteristics of NDPH have not been well studied in Japan.
      The purpose of this study is to investigate the clinical characteristics of the
      primary NDPH. Twenty-one men and twenty-two women with primary NDPH, aged 14 to
      73 years were diagnosed at Toyonaka Municipal Hospital from November 1997 to
      April 2003. Age of the onset ranged from 13 to 73 years (mean, 34.8). The onset
      of headache occurred in relation to a stressful life event in 16%, a systemic
      infection in 12% and an extracranial surgery in 7%. Any precipitating events
      could not be identified in approximately two-third of patients (65%). Quality of
      the headache was described as dull and/or pressure-like sensation in 91%,
      throbbing and/or pulsating sensation in 28%. NDPH needs further study, because it
      appears to be one of the most refractory headaches.

PMID- 14727559
TI  - [Two distinct types of neuropathy associated with Sjogren's syndrome developed in
      one patient. The importance of the selection of an appropriate therapeutic
      regimen].
AB  - A 62-year-old woman was admitted to our hospital because of muscle weakness and
      sensory disturbance in extremities. She showed weakness, muscle atrophy and
      sensory abnormality in four limbs with patchy distribution, suggesting
      involvement of multiple peripheral nerve trunks. Serum titers of anti-SS-A, SS-B,
      and antinuclear antibody were elevated. Sural nerve biopsy showed recanalization
      and lymphocytic infiltration in the epineural small vessels, suggesting the
      presence of vasculitis. She was diagnosed as having vasculitic neuropathy
      complicated with Sjogren's syndrome. Methylprednisolone pulse therapy followed by
      oral prednisolone was started and these symptoms gradually improved in one month.
      At age 63, she felt dysesthesia in the right lower limb and this sensory
      abnormality spreaded to upper limbs. Two years later, she was admitted again due
      to clumsiness of hands and gait disturbance. Neurological examination showed
      decreased vibration and position sense of lower limbs and limb ataxia in addition
      to dysesthesia. Electrophysiological studies demonstrated significant decrease in
      amplitude of sensory nerve action potentials and delayed somatosensory evoked
      potentials after N13, indicating impairment of dorsal root ganglions. She was
      treated with intravenous immunoglobulin (400 mg/kg, total 15 g/day) for 5 days.
      One week later, sensory ataxia was improved. It has been known that Sjogren's
      syndrome is often complicate with various types of neuropathies including
      vasculitic neuropathy and sensory neuropathy. Our patient developed these two
      different types of neuropathies which were dramatically improved after two
      different therapeutic regimens; indicating the importance to select a suitable
      treatment regimen in accordance with the mechanism of neuropathy associated with
      Sjogren's syndrome.

PMID- 14727560
TI  - [A case of thymoma-associated myasthenia gravis with antibodies against
      interferon-alpha--a clinico-immunological follow up of the symptoms and its
      titer].
AB  - A 73-year-old woman developed myasthenia gravis (MG) with thymoma. She had a very
      high level of serum antibodies against interferon-alfa (IFN-alpha). We observed
      the changes to her clinical symptoms and titer of the antibody during therapeutic
      course. Although she underwent thymectomy, intravenous methylprednisolone
      therapy, and oral tacrolimus administration, MG symptoms of the patient were not
      significantly improved and the antibody titer remained at a high level. IFN-alpha
      is a potent immunomodulating cytokine that regulates MHC class II expression on
      antigen presenting cells and activities of NK cells, B cells, and
      helper/suppressor T cells. This case suggests that IFN-alpha related
      immunological perturbation participates in the pathogenesis of thymoma-associated
      myasthenia gravis.

PMID- 14727561
TI  - [Ataxic Guillain-Barre syndrome with delayed facial diplegia].
AB  - We described a patient with ataxic Guillain-Barre syndrome who subsequently
      developed facial diplegia. A 38-year-old man developed ataxia, distal limb
      paresthesias, mild dysphagia, urinary retention and orthostatic hypotension a
      week after an episode of laryngitis. He had high titers of serum anti-GQ1b, anti
      GD1b, anti-GM1b, anti-GT1a, and anti-GD1a IgG antibodies during the acute phase.
      Although the initial symptoms markedly improved by intravenous immunoglobulin
      therapy, asymmetric facial diplegia subsequently occurred and remained longer
      than ataxia. Similar course of facial nerve palsy has been reported in patients
      with Fisher syndrome. Common pathophysiological mechanism may function in the
      development of delayed facial diplegia in Fisher syndrome and ataxic Guillain
      Barre syndrome.

PMID- 14727562
TI  - [A case of subacute combined degeneration with normal serum vitamin B12 level].
AB  - A 40-year-old woman was admitted to our hospital because of pancytopenia with
      megaloblastic anemia. Two months later she complained of rapidly progressive gait
      disturbance and numbness in the distal part of limbs. She also told that her hair
      had turned totally gray in the third decade. Neurologically, mental state,
      cranial nerves and cerebellar functions were normal. Superficial sensations were
      impaired below the lower thoracic level and deep sensations were completely lost
      in the lower limbs. Moderate weakness was found in the lower limbs,
      symmetrically. Deep tendon reflexes were diminished in the upper limbs and absent
      in the lower limbs. Babinski's reflex was positive bilaterally. MR images of the
      spinal cord showed hyperintensity in the posterior column below the thoracic
      cord. Although the serum level of vitamin B12 was within normal range, serum
      homocysteine level was elevated markedly. Under the diagnosis of subacute
      combined degeneration (SCD) due to possible vitamin B12 deficiency, the treatment
      with intravenous injections of 500 micrograms/day of mecobalamin was undertaken.
      Muscle strength and sensory impairment improved progressively and she became able
      to walk with a cane. The coloration of her gray hair was also noted. After
      treatment, pancytopenia and megaloblastic anemia also markedly improved. Vitamin
      B12 became high in serum concentration and the serum level of homocysteine became
      normal. These clinical and laboratory findings support the diagnosis of SCD with
      normal serum level of vitamin B12 in our case, suggesting that the level of
      vitamin B12 in serum does not always correlate with that in tissue and,
      therefore, SCD should not be excluded just only by the reason of normal serum
      vitamin B12 level.

PMID- 14727563
TI  - [Dropped head plus syndrome; a case report].
AB  - We reported a patient with so-called "dropped head plus syndrome", a non
      progressive myopathy characterized by striking neck extensor weakness followed by
      progressive limb weakness which is well controlled by azathioprine. This 74-year
      old man complained of neck and shoulder fatigue followed by progressive neck
      extensor weakness over 7 months. On physical examination, neck extensor strength
      was 4/5 on the MMT scale, but the remainder of the neurological examination and
      blood tests were normal. Needle EMG showed myopathic changes in the right
      trapezius and biceps brachialis muscles. Without any treatment, he developed
      weakness of upper and lower limb muscles about 8 months later, and Gowers' sign
      was positive. Blood test and needle EMG was unchanged. Muscle biopsy of the left
      trapezius, deltoid and supraspinatus muscles disclosed nonspecific myopathic
      changes consisting of variation in fiber size with disorganized intermyofibrillar
      networks in all the fibers, and there were rimmed vacuoles in some fibers of the
      deltoid muscle. There was no change on corticosteroids, but there was a dramatic
      improvement with azathioprine and his muscle symptoms disappeared. We, therefore,
      made the diagnosis of "dropped head plus syndrome". This appears to be the first
      such case in Japan.

PMID- 14727564
TI  - [Preferential distal muscle involvement in case of oculopharyngeal muscular
      dystrophy with (GCG) 13 expansion].
AB  - We reported a 52-year-old woman with oculopharyngeal muscular dystrophy (OPMD)
      harboring expanded (GCG) 13 mutation of the poly (A) binding protein 2 gene. She
      presented not only ptosis and dysphagia but distal dominant muscle atrophy in
      four extremities. CT demonstrated distal muscle atrophy with marked fat
      replacement in the biceps femoris, semitendinosus, membraneous, soleus, and
      gastrocnemius muscles. Although OPMD is considered to be a muscle disease, this
      patient showed even neurogenic features in the electrophysiological and
      pathological findings. Although previous reports indicate that OPMD is
      genetically homogeneous disease, some cases with OPMD may show some atypical
      features associated with neurogenic involvement.

PMID- 14727565
TI  - [A case of mitochondrial myopathy with external ophthalmoplegia and ataxic
      neuropathy].
AB  - We report a 70-year-old woman with bilateral optic atrophy, external
      ophthalmoplegia, bilateral blepharoptosis, and sensory ataxic neuropathy. She had
      a visual disturbance since childhood. She had dysarthria and gait disturbance at
      28 years old. She had bilateral blepharoptosis, marked gait disturbance and
      dysphagia at 50. On neurological examination, external ophthalmoplegia, bilateral
      blepharoptosis, mild weakness and muscular atrophy of promixal muscles,
      hyporeflexia, positive Romberg sign, glove and stocking type sensory disturbance
      including hypesthesia, hypalgesia, and bathyhypesthesia were found. She did not
      show pigmented retinopathy, cognitive dysfunctions, hearing loss, cerebellar
      ataxia, Hoffman reflex nor Babinski sign. She did not show increased lactic acid
      nor pyruvic acid in the cerebrospinal fluid but mild increase of pyruvic acid
      (1.0 mg/dl) in her serum. The conduction velocity and amplitude of CMAP of tibial
      nerve was 37.4 m/sec and 2.9 mV, respectively. The SNAP of ulner and sural nerve
      were not evoked. Brain MRI showed no pathological findings. Muscle biopsy from
      the biceps muscle showed many ragged-red fibers (5.3%) and some fibers with
      decreased or absent COX activity. Sural nerve biopsy showed a marked loss of
      large myelinated fibers with thin myelinated fibers, and onion-bulb formation.
      The clinical findings of our patient is similar to that of SANDO (the triad of
      sensory ataxic neuropathy, dysarthria, and ophthalmoparesis), however, large
      mtDNA deletion reported by Fadic in patients with SANDO was not found in our
      patient. It might be possible that her mtDNA deletion is small or point mutation
      is existed.

PMID- 14727566
TI  - [A case of very-long-chain acyl-CoA dehydrogenase deficiency with adolescent
      onset being diagnosed by immunostain of biopsy muscle].
AB  - We report a case of myopathic form of very-long-chain acyl-CoA dehydrogenase
      (VLCAD) deficiency with adolescent onset which presented with recurrent
      rhabdomyolysis and was diagnosed by immunostain of biopsy muscle. She was an 18
      year-old woman who showed recurrent episodes of rhabdomyolysis after exercise
      since the age of 15. The diagnosis was made by the immunostain using anti-VLCAD
      antibody and the measurement of acyl-CoA dehydrogenase activity for the biopsy
      muscle. Her elder sister had also showed recurrent episodes of rhabdomyolysis at
      least two times. The analysis of genomic DNA on blood samples of the patient and
      her sister was performed and the same mutations were identified. Hence, these
      sister were revealed to have VLCAD deficiency. We should keep in mind this
      disorder for those presenting with recurrent rhabdomyolysis. In addition, as far
      as we know, this is the first report that a correct diagnosis was obtained by
      immunostain. Immunostain is probably a useful diagnostic procedure to identify an
      uncommon myopathy.

PMID- 14727567
TI  - [A case of solitary and unilateral trochlear nerve palsy due to a blunt head
      impact].
AB  - A case of solitary and unilateral trochlear nerve palsy following a minor, blunt
      head impact is reported. A 72-year-old man fell down backwards from the top of a
      staircase having 13 steps and hit his right parietal head and shoulder. Routine
      neurological examination revealed no remarkable findings, however, the subject
      complained of double vision when he focused downwards. The computed tomography
      four hours after the initial impact showed a localized small high-density lesion
      on the left quadrigminal cistern. The magnetic resonance imaging also indicated
      subarachnoid bleeding expressed by the low-intensity area in T2 weighted images
      in the same place. There was no evidence of any contusion within the midbrain.
      Hess chart test clearly showed solitary left superior oblique muscle palsy. The
      manner of the injury was thought to be quite typical, since he had hit his right
      parietal area up-side-down when falling, that is, the accelerated force acted as
      an impact against the firm floor. This impact caused the midbrain concussion
      against the cerebellar tentorial notch resulting in a localized subarachnoid
      hemorrhage which caused the unilateral trochlear nerve palsy.

PMID- 14727568
TI  - [Permanent values of clinical practice].

PMID- 14727569
TI  - [Radiologic evaluation of idiopathic congenital clubfoot and its clinical
      correlation in Codivilla's surgical technique].
AB  - Thirty-seven patients (52 idiopathic clubfeet) were treated with Codivilla's
      technique between 1971 and 1985. Radiological measurements and clinical
      evaluation before and after surgery were performed; a correlation was carried out
      between these evaluations and personal satisfaction. The results were rated as
      follows: poor in 4 feet (7.7%), fair in 18 feet (34.6%), good in 24 feet (46.2%)
      and excellent in 6 feet (11.5%) with a total percentage of satisfactory results
      amounting to 57.7%. Our conclusion is that when the indications are properly
      established, Codivilla's technique is a good procedure to correct clubfoot.

PMID- 14727570
TI  - [Thoracic metastasis of breast carcinoma. Current status].
AB  - Breast cancer is a common pathology. It is clinically considered as a localized
      or regionally developing illness at the time of diagnosis, but the appearance of
      metastases is a frequent complication. Patients are commonly referred with local
      or regional recurrence of the disease. Invasive metastatic disease found in the
      chest can be differentiated according to area as follows: pulmonary parenchyma
      (nodes and/or carcinomatosis lymphangitis), pleural cavity (pleural effusion
      and/or tumor), pericardial effusion and the thoracic wall. The appearance of
      pulmonary parenchymal metastases secondary to breast cancer can be further
      categorized into three types, neoplastic lymphangitis, multiple and single
      pulmonary nodes. Pleural effusion is the commonest thoracic affection in patients
      with this pathology. It is accepted that 46% of patients with disseminating
      breast cancers will develop pleural metastases where the presentation is
      pericardial effusion, and possible cardiac tamponade. Finally, metastatic disease
      may be found localized to within the thoracic wall. Breast cancer can produce
      diverse problems in the thoracic wall, and local recurrence is most frequent at
      the mastectomy site.

PMID- 14727571
TI  - [Von Willebrand factor as an intermediate between hemostasis and angiogenesis of
      tumor origin].
AB  - Cancer patients often show an imbalance condition between coagulation system and
      fibrinolysis which causes a prothrombotic state. Different molecular factors like
      von Willebrand factor (vWf), presenting higher plasmatic rates in these patients,
      play an important role in this situation. During active angiogenesis taking place
      in tumor growth, the vascular endothelial growth factor (VEGF) and the fibroblast
      growth factor (FGF-2) contribute to the proliferation and differentiation of
      endothelial tissue, the main vWf producer, promoting increased rates of vWf in
      the serum of neoplastic patients. Recently vWf's contribution to tumor cells and
      platelet adhesion has been described. In this process, the discovery of platelet,
      endothelial and tumor cell membrane integrins and their implication in cellular
      adhesion has represented a major step in demonstrating how blood clotting and
      platelet aggregation are mediated by tumor cell and platelet linkage. Migration
      properties acquired by tumor cells as a result of this binding have been also
      pointed out. Clinical trials show higher rates of plasmatic vWf in cancer
      patients the more advanced clinical and radiological stage they present
      (metastasic versus localized). Moreover, higher pre-surgical serum vWf rates in
      patients can be used to predict poorer survival after resection surgery. vWf high
      molecular weight multimers have been also related to a cleavage protease
      deficiency in the serum of the oncologic population. The promising results of
      antiaggregation/anticoagulation therapies in these patients permit us to envisage
      new therapeutic targets.

PMID- 14727572
TI  - [Toll type receptors: molecular bases of the relationship between innate and
      adaptation responses of the immune system].
AB  - Microbes have on their surface molecular patterns that are common among a broad
      range of pathogens. These patterns are recognized by a wide variety of cellular
      receptors, the most important of which are a family of transmembrane proteins
      termed "Toll-like receptors" (TLR). TLRs are pattern-recognition receptors that
      have key roles in detecting pathogens and initiating inflammatory responses. The
      receptor of Gram negative bacterial LPS, TLR4, is the best characterized member
      of the TLR family. So far, ten mammalian toll-like receptors (TLR1-TLR10) have
      been identified. Recent studies revealed that the TLR signaling pathway is a
      critical mediator of sepsis. An understanding of TLRs and their signaling pathway
      will reveal a therapeutic target in sepsis and other immune mediated diseases.

PMID- 14727573
TI  - [Human pluripotent stems cells I].
AB  - In the last few years, the great progress of certain fields, such as molecular
      biology and development, has allowed a detailed knowledge of mechanisms
      implicated in cellular programing. This has permitted a rapid and unexpected
      advance in therapeutic cellular strategies. Thus, it has been possible to
      discover mechanisms involved in cellular differentiation and therefore has opened
      possibilities for human cellular manipulation and function replacement of damaged
      cells. Embryonic stem cells, have been obtained from the embryoblast. A lot of
      types of cellular lineages that include neurons, glial cells, pancreatic islets
      cells, hepatic cells, osteoblast and adipocytes, have been derived from mouse
      embryonic stem cells. In the same way, cellular lineages have been obtained by
      nuclear transference techniques capable of generating embryonic clones. Some
      scientist intend to evade by this approach, the bioethic reproval for human
      cloning, emphasizing that this is a "therapeutic cloning". In the present work,
      we propose to analyze mechanisms that permit stem cells to be pluripotential and
      discuss the ethical use of embryos as a source for stem cells with therapeutic
      potential.

PMID- 14727574
TI  - [Multiple pulmonary metastasis and exacerbation of dyspnea].

PMID- 14727575
TI  - [Beyond autonomy].

PMID- 14727577
TI  - Quick response to food poisoning.

PMID- 14727576
TI  - [Tiotropium].

PMID- 14727578
TI  - More help, less harm with effective steroid use.

PMID- 14727579
TI  - Angina: a red flag for heart disease.

PMID- 14727580
TI  - The ultimate gift: making an organ donation.

PMID- 14727581
TI  - What should I do about protein in my urine?

PMID- 14727582
TI  - How can I prevent mild heartburn?

PMID- 14727583
TI  - Newest insulin delivery options.

PMID- 14727584
TI  - Levelheaded answers to light-headedness.

PMID- 14727585
TI  - Clarifying the causes of blurry vision.

PMID- 14727586
TI  - Solutions for declining bladder control.

PMID- 14727588
TI  - Is genetically modified food safe?

PMID- 14727587
TI  - What is the difference between oxygen supplementation and mechanical ventilation?

PMID- 14727589
TI  - Avoiding "economy class syndrome".

PMID- 14727590
TI  - Should you be screened for ovarian cancer?

PMID- 14727592
TI  - Clearing up confusion about prostatitis.

PMID- 14727591
TI  - Your stroke survival action plan.

PMID- 14727593
TI  - How can I gain back the weight I recently lost for no apparent reason, and what
      might have caused me to lose weight in the first place?

PMID- 14727594
TI  - What is pulmonary hypertension and how should it be treated?

PMID- 14727595
TI  - And you think saturated is bad...

PMID- 14727596
TI  - Are you taking the right heart disease drugs?

PMID- 14727597
TI  - No bones about it: preventing fractures.

PMID- 14727598
TI  - A prescription for reducing stress in stressful times.

PMID- 14727600
TI  - Cutting your diabetes risk in half.

PMID- 14727599
TI  - How can I reduce the swelling in my arm, which started after I had a mastectomy?

PMID- 14727601
TI  - Standard NSAIDs vs. COX-2 inhibitors.

PMID- 14727602
TI  - Working through traumatic events.

PMID- 14727603
TI  - The best diet for cancer survivors.

PMID- 14727604
TI  - When and how should high triglycerides be treated?

PMID- 14727605
TI  - [Advances in the study on medicinal herbs of Urtica L].

PMID- 14727606
TI  - [Not Available].

PMID- 14727608
TI  - [Not Available].

PMID- 14727607
TI  - [Post graduate studies in child health--a new teaching proposal].

PMID- 14727610
TI  - [Therapeutic abortion].

PMID- 14727609
TI  - [Not Available].

PMID- 14727611
TI  - Patient's death from vCJD may be linked to blood transfusion. Committee to
      discuss need for further precautions to prevent possible vCJD transmission
      through blood.

PMID- 14727612
TI  - Publishers face backlash over rising subscription costs. High prices have led
      some US institutions to cancel subscriptions to, or even boycott, scientific
      journals.

PMID- 14727613
TI  - Tobacco company defends safety of curing process.

PMID- 14727614
TI  - Chilean TV channels in court over AIDS ads.

PMID- 14727615
TI  - Increased funding for health could help prevent conflict.

PMID- 14727616
TI  - Argentine murder leads to crackdown on doctors.

PMID- 14727617
TI  - [Not Available].

PMID- 14727618
TI  - [Not Available].

PMID- 14727619
TI  - China promises to dash hopes of tobacco industry giants. By signing up to WHO's
      tobacco treaty, China pledges to tighten controls on cigarette industry.

PMID- 14727620
TI  - [Not Available].

PMID- 14727621
TI  - [Infant mortality in Brazil].

PMID- 14727622
TI  - [Title of the specialist in pediatric 1996].

PMID- 14727623
TI  - [Not Available].

PMID- 14727624
TI  - Trauma-induced perforating folliculitis.

PMID- 14727625
TI  - Bifurcated, modular syntheses of chiral annulet triazacyclononanes.
AB  - Three chiral 2,6-disubstituted tri-N-methyl azamacrocycles have been prepared by
      modular methods. These macrocycles were accessed from three chiral 1,4,7
      triazaheptanes intermediates that were prepared by two independent routes. The
      first of these routes involved the benzylamine opening of chiral tosyl aziridines
      followed by debenzylation but was problematic on solubility grounds. A second,
      more effective, route was developed which avoided debenzylation by using ammonia
      in the nucleophilic opening of chiral tosyl aziridines.

PMID- 14727626
TI  - Where is the site that ATP7B transports copper within hepatocytes?

PMID- 14727627
TI  - Can proton pump inhibitors be blamed for the rising incidence of esophageal
      cancer?

PMID- 14727628
TI  - Biomimetic total synthesis of forbesione and desoxymorellin utilizing a tandem
      Claisen/Diels--Alder/Claisen rearrangement.
AB  - A concise synthesis of forbesione (1) and desoxymorellin (3) is presented.
      Central to the strategy is a biomimetic Claisen/Diels-Alder/Claisen reaction
      cascade that proceeds in a regioselective manner and produces the desired
      scaffold exclusively. The observed regioselectivity and product distribution of
      the Claisen/Diels-Alder/Claisen reaction are attributed to the electronic effects
      of the xanthone oxygen (O10), the C9 carbonyl group and the nature of the C1
      functionality.

PMID- 14727629
TI  - Colorectal cancer incidence differs within ethnic Chinese.

PMID- 14727630
TI  - NSAIDS and esophageal cancer.

PMID- 14727631
TI  - Syntheses of selectively fluorinated cyclodecenones: the first deployment of the
      neutral oxy-Cope rearrangement in organofluorine chemistry.
AB  - Metallated haloalkenes were used to open epoxides in moderate to good yield. The
      homoallylic alcohols obtained underwent Swern oxidation to afford three
      gamma,gamma-difluorinated beta,gamma-enones, which reacted with either
      vinyllithium,2-lithio-2H-dihydropyran or another metallated haloalkene to afford
      substituted trans-1,2-divinylcyclohexanols of different degrees of stability.
      These intermediates underwent neutral thermal oxy-Cope rearrangements when heated
      in xylene in Ace tubes. The first-formed enols ketonised without loss of HF to
      afford a range of cyclodecenones in moderate to good yield; X-ray crystallography
      was used extensively for product characterisation. All substrates rearranged more
      rapidly than a cis/trans mixture of 1,2-divinylcyclohexanols.

PMID- 14727632
TI  - The lack of HER-2/neu oncogene amplification in colorectal malignancies.

PMID- 14727633
TI  - Pressure control of enantiodifferentiating photoisomerization of cyclooctenes
      sensitized by chiral benzenepolycarboxylates. The origin of discontinuous
      pressure dependence of the optical yield.
AB  - Pressure effects on enantiodifferentiating geometrical photoisomerizations of (Z)
      cyclooctene and (Z,Z)-cycloocta-1,5-diene sensitized by chiral benzene-1,2,4,5
      tetracarboxylate were investigated over a pressure range of 0.1-750 MPa.
      Enantiomeric excesses (ee's) of the (E)- and (E.Z)-isomers obtained displayed
      discontinuous pressure dependencies, affording distinctly different differential
      activation volumes (delta delta V++) for each range, indicating alteration of the
      enantiodifferentiation mechanism. The switching of delta delta V++ occurred at
      essentially the same pressures of 200 and 400 MPa, which are shared by all the
      chiral sensitizers, irrespective of the chiral auxiliary employed. Circular
      dichroism spectral examinations at pressures of up to 400 MPa also revealed that
      the chiral sensitizers undergo discontinuous conformational changes at 200 MPa,
      which most likely lead to switching of the enantiodifferentiating sensitization
      mechanism in the exciplex intermediate.

PMID- 14727634
TI  - Clinical relevance of hepatitis B virus genotypes Ba and Bj in Taiwan.

PMID- 14727635
TI  - No-Aspirin (NCX 4016).

PMID- 14727637
TI  - Lack of association between the C3435T MDR1 gene polymorphism and inflammatory
      bowel disease in two independent Northern European populations.

PMID- 14727636
TI  - Photolysis of regioisomeric diazides of 1,2-diphenylacetylenes studies by matrix
      isolation spectroscopy and DFT calculations.
AB  - A series of diazides of 1,2-diphenylacetylenes was photolyzed in matrices at low
      temperature and transient photoproducts were characterized by using IR, UV/vis
      methods combined with ESR studies. Theoretical calculations were also used to
      understand the experimental findings. The introduction of phenylethynyl groups on
      phenyl azides has little effect on the photochemical pathway. Thus, upon
      photoexcitation, (phenylethynyl)phenyl azides afforded the corresponding triplet
      nitrene, which is in photoequilibrium with the corresponding
      azacycloheptatetraene. In marked contrast, azidophenylethynyl groups exhibited a
      dramatic effect not only on the photochemical pathway of phenyl azides but also
      on the electronic and molecular structure of the photoproducts. The patterns of
      the effect depended upon the relative position of azide groups in the
      diphenylacetylene unit. Whenever two azide groups were situated in a conjugating
      position with respect to each other, as in p,p'-, o,o'-, and p,o'-bis(azides),
      the azides always resulted in the formation of a quinoidal diimine diradical in
      which unpaired electrons were extensively delocalizedin the pi-conjugation. The
      situation changed rather dramatically when azide groups were introduced in the
      meta position. Thus, the formation of azacycloheptatetraene was noted in the
      photolysis of the m.m'-isomer. ESR studies indicated the generation of a quintet
      state that was shown to be a thermally populated state with a very small energy
      gap of ca. 100 cal mol(-1). The m,p'-isomer was shown to be an excellent
      precursor for the high-spin quintet dinitrene. The IR spectra of the photoproduct
      showed no bands ascribable to azacycloheptatetraene. The observed spectra were in
      good agreement with that calculated for the quintet state. Strong EPR signals
      assignable to the quintet state were observed, along with rather weak signals due
      to mononitrenes. Moreover, the quintet bis(nitrene) was rather photostable under
      these conditions.

PMID- 14727638
TI  - Synthesis, structural determination and dynamic behavior of 2-chloro-4,6
      bis(pyrazolylamino)-1,3,5-triazines.
AB  - A series of 2-chloro-4,6-bis(pyrazolylamino)-1,3,5-triazines with applications in
      crystal engineering have been prepared. At low temperature, the presence of two
      or three isomers has been detected and these assigned to 4,6-diamino-1,3,5
      triazine structures on the basis of comparison with model compounds. 2D-Exchange
      spectroscopy studies in various solvents and at different temperatures have been
      used to determine the equilibrium constants and the activation free energies of
      the restricted rotation about the amino-triazine bond. A plot of the activation
      free energy versus temperature showed a good linear correlation and confirmed
      that the same process is present in all of the compounds under investigation.
      Comparison with model compounds also confirmed both the occurrence of the
      restricted rotation and the 4,6-diamino-1,3,5-triazine tautomerism for triazines
      1-4 in solution. The structure of compound 1 has been determined in the solid
      state by X-ray crystallography and consists ofa 4,6-diamino- 1,3,5-triazine
      structure stabilized by intra and intermolecular hydrogen bonds.

PMID- 14727639
TI  - Gastrin-induced hyperproliferation in Barrett's esophagus.

PMID- 14727640
TI  - Is intrahepatic cholestasis of pregnancy an MDR3-related disease?

PMID- 14727641
TI  - 3,3-Diethyl-and 3,3-dibenzyl-1,2-diferrocenylcyclopropenes.
AB  - Reactions of 2,3-diferrocenylcyclopropenone 1 with ethyl- and benzylmagnesium
      chlorides afford 3,3-diethyl-and 3,3-dibenzyl- 1,2-diferrocenylcyclopropenes 2
      and 3, respectively, and products of nucleophilic opening of the three-membered
      ring resulting from the addition of RMgCl to the carbonyl group, viz., saturated
      ketones(4,5-diferrocenylheptan-3-ones 4a,b and 3,4-diferrocenyl-1,5
      diphenylpentan-2-ones 5a,b as ca. 3: 1 mixtures of two diastereomers) and other
      products. The spatial structures of compounds 2 and 4a were established by X-ray
      diffraction analysis of single crystals. Protonation of the cyclopropenes 2 and 3
      with tetrafluoroboric acid at -40 degrees C yields the corresponding 3,3-dialkyl
      1 ,2-diferrocenylcyclopropylium tetrafluoroborates. Transformation of the latter
      into diferrocenylallylic cations upon increasing the temperature to 20 degrees C
      and their eprotonation under the action of N,N-dimethylaniline were studied.
      Electrochemical investigation of 1 and 2 shows that in both complexes the
      cyclopropene spacer allows electronic communication between the two outer
      ferrocenyl groups, this being notably greater for 2 than for 1.

PMID- 14727642
TI  - Synthesis of light-harvesting dendrimers focally anchored with crown ethers or
      terpyridine ligands.
AB  - Crown ethers and terpyridine ligands have been successfully attached to the focal
      point of light harvesting phenylacetylene monodendrons through Pd-catalyzed
      coupling reactions. The structures of these functional monodendrons were
      characterized by 1H and 13C NMR spectroscopy, mass spectrometry and elemental
      analysis. Such binding-ligand anchored dendrons exhibit broad absorption, large
      molar extenction coefficients and high fluoresence quantum yields. Coordination
      of crown ethers with alkali ions results in a significant increase in absorption
      strength in the UV range, but little alteration in either intensity or position
      of fluorescence emission. Coordination of terpyridine ligands with Ru2+, however,
      does efficiently quench the fluorescence from the dendrons,albeit only the
      smallest dendron exhibits efficient binding.

PMID- 14727643
TI  - "The great debate" 1: Smoking, lung cancer, and cancer epidemiology.
AB  - During the first decades of the 20th century the lung cancer death rate increased
      sharply in developed countries, including Canada. An association with cigarette
      smoking was suspected. Between 1950 and 1960 many epidemiological studies
      confirmed this association. The validity of these studies was attacked fiercely
      by some renowned statistics. The resulting debate sharpened the methodological
      and analytical rigour of epidemiological studies. Epidemiology became an
      indispensable tool in cancer prevention.

PMID- 14727644
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14727645
TI  - "No place like home": Gender, family, and the politics of home care in post-world
      war II Ontario.
AB  - Since the early 1990s home care increasingly has emerged as a favoured policy
      response to the growing costs which an aging population poses for our health care
      system. This paper explores the early history of home care for the elderly in
      Ontario during the first three decades after World War II. It demonstrates that
      policy debates over the merits of home versus institutional care for the elderly,
      and community-based over hospital-based approaches to home care are not recent
      phenomenon but have been on going since the 1940s within the public health and
      social services sector. The paper examines why home care failed for so long to
      develop beyond the margins of Ontario's highly institutionalized health care
      system. It also explores how earlier visions of community-based home care,
      designed to help the elderly age in place, increasingly were obscured by an
      exclusive preoccupation with home care's "cost effectiveness" as an alternative
      to hospital or residential care, a rationale which discounted home care's costs
      to unpaid and principally female care givers. The paper concludes that the
      Ontario health ministry's systematic devaluing of caregiving and home maker
      skills, the fear of undermining the family's willingness to provide care, as well
      as the failure to develop effective mechanisms for integrated regional health
      care planning, also impeded the progress of home care's development before the
      1980s.

PMID- 14727646
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14727647
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14727649
TI  - [Not Available].

PMID- 14727648
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14727651
TI  - [Not Available].

PMID- 14727650
TI  - Models and microbiology: Pasteur and the body.
AB  - Louis Pasteur developed a model of the body as a culture vessel in the late 1870s
      as an explanation of both natural and acquired immunity, and other investigators
      quickly applied the model in the explanation of other microbiological phenomena,
      principally the tissue tropism seen in the normal and the pathological flora.
      This paper will argue that although Pasteur quickly abandoned the model, it
      persisted as an explanation of tissue tropism for nearly 70 years, structuring
      the interpretation of data by and guiding the research of a diverse group of
      microbiological researchers.

PMID- 14727656
TI  - Space life sciences: structure and dynamics of the global space radiation field
      at aircraft altitudes.

PMID- 14727655
TI  - Duodenal duplication cysts.

PMID- 14727657
TI  - Overview of atmospheric ionizing radiation (AIR) research: SST-present.
AB  - The Supersonic Transport (SST) program, proposed in 1961, first raised concern
      for the exposure of pregnant occupants by solar energetic particles (SEP), and
      neutrons were suspected to have a main role in particle propagation deep into the
      atmosphere. An eight-year flight program confirmed the role of SEP as a
      significant hazard and of the neutrons as contributing over half of the galactic
      cosmic ray exposures, with the largest contribution from neutrons above 10 MeV.
      The FAA Advisory Committee on the Radiobiological Aspects of the SST provided
      operational requirements. The more recent lowering of ICRP-recommended exposure
      limits (1990) with the classification of aircrew as "radiation workers" renewed
      interest in GCR background exposures at commercial flight altitudes and
      stimulated epidemiological studies in Europe, Japan, Canada and the USA. The
      proposed development of a High Speed Civil Transport (HSCT) required validation
      of the role of high-energy neutrons, and this resulted in ER-2 flights at solar
      minimum (June 1997) and studies on effects of aircraft materials on interior
      exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted
      in legislation for health compensation in year 2000 and recent European aircrew
      epidemiological studies of health outcomes bring renewed interest in aircraft
      radiation exposures. As improved radiation models become available, it is
      imperative that a corresponding epidemiological program of US aircrew be
      implemented.

PMID- 14727658
TI  - A new dynamical atmospheric ionizing radiation (AIR) model for epidemiological
      studies.
AB  - A new Atmospheric Ionizing Radiation (AIR) model is currently being developed for
      use in radiation dose evaluation in epidemiological studies targeted to
      atmospheric flight personnel such as civilian airlines crewmembers. The model
      will allow computing values for biologically relevant parameters, e.g. dose
      equivalent and effective dose, for individual flights from 1945. Each flight is
      described by its actual three dimensional flight profile, i.e. geographic
      coordinates and altitudes varying with time. Solar modulated primary particles
      are filtered with a new analytical fully angular dependent geomagnetic cut off
      rigidity model, as a function of latitude, longitude, arrival direction, altitude
      and time. The particle transport results have been obtained with a technique
      based on the three-dimensional Monte Carlo transport code FLUKA, with a special
      procedure to deal with HZE particles. Particle fluxes are transformed into dose
      related quantities and then integrated all along the flight path to obtain the
      overall flight dose. Preliminary validations of the particle transport technique
      using data from the AIR Project ER-2 flight campaign of measurements are
      encouraging. Future efforts will deal with modeling of the effects of the
      aircraft structure as well as inclusion of solar particle events.

PMID- 14727659
TI  - Preliminary validation of computational procedures for a new atmospheric ionizing
      radiation (AIR) model.
AB  - A new computational procedure to determine particle fluxes in the Earth's
      atmosphere is presented. The primary cosmic ray spectrum has been modeled through
      an analysis of simultaneous proton and helium measurements made on high altitude
      balloon flights and spacecraft. An improved global fit to the data was achieved
      through applying a unique technique utilizing the Fokker-Plank equation with a
      non-linear rigidity-dependent diffusion coefficient. The propagation of primary
      particles through the Earth's atmosphere is calculated with a three-dimensional
      Monte Carlo transport program called FLUKA. Primary protons and helium nuclei
      (alphas) are generated within the rigidity range of 0.5 GV-20 TV uniform in cos2
      theta. For a given location, primaries above the effective cutoff rigidity are
      transported through the atmosphere. Alpha particles are initially transported
      with a separate package called HEAVY to simulate fragmentation. This package
      interfaces with FLUKA to provide interaction starting points for each nucleon
      originating from a helium nucleus. Results from this calculation are presented
      and compared to measurements.

PMID- 14727660
TI  - Recent results form measurements of the energy spectrum of cosmic-ray induced
      neutrons aboard an ER-2 airplane and on the ground.
AB  - Crews of future high-altitude commercial aircraft may be significantly exposed to
      atmospheric cosmic radiation from galactic cosmic rays (GCR). To help determine
      such exposures, the Atmospheric Ionizing Radiation Project, an international
      collaboration of 15 laboratories, made simultaneous radiation measurements with
      14 instruments on a NASA ER-2 high-altitude aircraft. The primary instrument was
      a sensitive extended-energy multisphere neutron spectrometer, which was also used
      to make measurements on the ground. Its detector responses were calculated for
      neutrons and charged hadrons at energies up to 100 GeV using the radiation
      transport code MCNPX. We have now recalculated the detector responses including
      the effects of the airplane structure. We are also using new FLUKA calculations
      of GCR-induced hadron spectra in the atmosphere to correct for spectrometer
      counts produced by charged hadrons. Neutron spectra are unfolded from the
      corrected measured count rates using the MAXED code. Results for the measured
      cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and
      neutron dose equivalent and effective dose rates, and their dependence on
      altitude and geomagnetic cutoff generally agree well with results from recent
      calculations of GCR-induced neutron spectra.

PMID- 14727661
TI  - Radiation measurements aboard NASA ER-2 high altitude aircraft with the Liulin-4J
      portable spectrometer.
AB  - The risks to aircrew health posed by prolonged exposure to low levels of ionizing
      radiation at aircraft altitudes have recently received renewed attention. Civil
      and military aircraft currently on the drawing board are expected to operate at
      higher altitudes (>12 km) and fly longer ranges than do existing aircraft,
      thereby exposing their crews to higher levels of ionizing radiation, for longer
      periods of time. We are currently carrying out dosimetric measurements of the
      ionizing radiation environment at approximately 20 km altitude using portable Si
      detectors aboard NASA's two ER-2 high altitude research aircraft. The
      instruments, Liulin-4J, have been extensively calibrated at several particle
      accelerators. With these instruments, we can measure not only absorbed dose, but
      also variation of the absorbed dose as a function of time. We report radiation
      dose measurements as function of time, altitude, and latitude for several ER-2
      missions.

PMID- 14727662
TI  - Cosmic ray measurements at aircraft altitudes and comparison with predictions of
      computer codes.
AB  - Extensive measurements of dose exposure of aircrew have been carried out in
      recent years using passive detectors on subsonic and supersonic air routes by
      DIAS (Dublin Institute for Advanced Studies). Studies were based on measurement
      of LET spectra using nuclear recoils produced in CR-39 nuclear track detectors by
      high energy neutrons and protons. The detectors were calibrated using energetic
      heavy ions. Data obtained were compared with the predictions of the EPCARD and
      CARI-6 codes. Good agreement has been found between the experimental and
      theoretical values.

PMID- 14727663
TI  - Long-term monitoring of the onboard aircraft exposure level with a Si-diode based
      spectrometer.
AB  - The radiation fields onboard aircraft are complex (EURADOS, 1996), and several
      methods are used to characterise them for radiation protection. We have tested a
      spectrometer based on Si-diode at different sources and accelerator facilities.
      The energy deposited in the diode is analysed to estimate the contribution of
      different radiations to dosimetry quantities. The spectrum of energy deposition
      events onboard aircraft is similar to that registered in the CERN high-energy
      reference field. We used this similarity to determine the correction factors to
      appreciate radiation protection quantities from the results of onboard
      measurements. During 2001-2002, the spectrometer was used to acquire measurements
      onboard commercial aircraft during five long-term exposures. All necessary flight
      parameters were acquired; thus permitting calculations of the onboard effective
      dose and/or ambient dose equivalent by means of both the CARI 6 and the EPCARD
      codes and comparison with the results of the measurements. It was found that the
      apparent ambient dose equivalent values from measured data are in reasonable
      agreement with the results of calculations. Quantitative analysis of this
      agreement as a function of flight parameters (geomagnetic position, solar
      activity variations, etc.) is presented. During one flight, an important solar
      event (GLE 60 on 15 April 2001) was recorded by the spectrometer. In some other
      cases the measurements during a Forbush decreases were acquired. These extremes
      were well registered by the equipment and the data obtained are analyzed.

PMID- 14727664
TI  - Assessing exposure to cosmic radiation on board aircraft.
AB  - The assessment of exposure to cosmic radiation on board aircraft is one of the
      preoccupations of organizations responsible for radiation protection. The cosmic
      radiation particle flux increases with altitude and latitude and depends on the
      solar activity. The radiation exposure has been estimated on several airlines
      using transatlantic, Siberian and transequatorial routes on board subsonic and
      supersonic aircraft, to illustrate the effect of these parameters. Measurements
      have been obtained with a tissue equivalent proportional counter using the
      microdosimetric technique. Data have been collected at maximum solar activity in
      1991-92 and at minimum in 1996-98. The lowest mean dose rate measured was 3
      microSv/h during a Paris-Buenos Aires flight in 1991; the highest was 6.6
      microSv/h during a Paris-Tokyo flight using a Siberian route and 9.7 microSv/h on
      Concorde in 1996-97. The mean quality factor is around 1.8. The corresponding
      annual effective dose, based on 700 hours of flight for subsonic aircraft and 300
      hours for Concorde, can be estimated between 2 mSv for least-exposed routes and 5
      mSv for more exposed routes.

PMID- 14727665
TI  - Analysis of the Cyclotron Facility calibration and aircraft dosimetry results
      from the LIULIN-3M instrument.
AB  - The LIULIN-3M instrument is a further development of the LIULIN dosimeter
      radiometer, used on the MIR spacestation during the 1988-1994 time period. The
      LIULIN-3M is designed for continuous monitoring of the radiation environment
      during the BION-12 satellite flight in 1999. A semiconductor detector with 1 mm
      thickness and cm2 area is contained in the instrument. Pulse high analysis
      technique is used to determine the energy losses in the detector. The final data
      from the instrument are the flux and the dose rate for the exposure time and 256
      channels of absorbed dose spectra based on the assumption that the particle flux
      is normal to the detector. The LIULIN-3M instrument was calibrated by proton
      fluxes with different energies at the Indiana University Cyclotron Facility in
      June 1997 and had been used for radiation measurements during commercial aircraft
      flights. The calibration procedure and some flight results are presented in this
      paper.

PMID- 14727666
TI  - The atmospheric radiation response to solar-particle-events.
AB  - High-energy solar particles, produced in association with solar flares and
      coronal mass ejections, occasionally bombard the earth's atmosphere. resulting in
      radiation intensities additional to the background cosmic radiation. Access of
      these particles to the earth's vicinity during times of geomagnetic disturbances
      are not adequately described by using static geomagnetic field models. These
      solar fluxes are also often distributed non uniformly in space, so that fluxes
      measured by satellites obtained at great distances from the earth and which
      sample large volumes of space around the earth cannot be used to predict fluxes
      locally at the earth's surface. We present here a method which uses the ground
      level neutron monitor counting rates as adjoint sources of the flux in the
      atmosphere immediately above them to obtain solar-particle effective dose rates
      as a function of position over the earth's surface. We have applied this approach
      to the large September 29-30, 1989 ground-level event (designated GLE 42) to
      obtain the magnitude and distribution of the solar-particle effective dose rate
      from an atypically large event. The results of these calculations clearly show
      the effect of the softer particle spectra associated with solar particle events,
      as compared with galactic cosmic rays, results in a greater sensitivity to the
      geomagnetic field, and, unlike cosmic rays, the near-absence of a "knee" near 60
      degrees geomagnetic latitude.

PMID- 14727667
TI  - Calculations and observations of solar particle enhancements to the radiation
      environment at aircraft altitudes.
AB  - Solar particle events can give greatly enhanced radiation at aircraft altitudes,
      but are both difficult to predict and to calculate retrospectively. This enhanced
      radiation can give significant dose to aircrew and greatly increase the rate of
      single event effects in avionics. Validation of calculations is required but only
      very few events have been measured in flight. The CREAM detector on Concorde
      detected the event of 29 September 1989 and also four periods of enhancement
      during the events of 19-24 October 1989. Instantaneous rates were enhanced by up
      to a factor ten compared with quiet-time cosmic rays, while flight-averages were
      enhanced by up to a factor six. Calculations are described for increases in
      radiation at aircraft altitudes using solar particle spectra in conjunction with
      Monte Carlo radiation transport codes. In order to obtain solar particle spectra
      with sufficient accuracy over the required energy range it is necessary to
      combine space data with measurements from a wide range of geomagnetically
      dispersed, ground-level neutron monitors. Such spectra have been obtained for 29
      September 1989 and 24 October 1989 and these are used to calculate enhancements
      that are compared with the data from CREAM on Concorde. The effect of cut-off
      rigidity suppression by geomagnetic activity is shown to be significant. For the
      largest event on record on 23 February 1956, there are no space data but there
      are data from a number of ground-level cosmic-ray detectors. Predictions for all
      events show very steep dependencies on both latitude and altitude. At high
      latitude and altitude (17 km) calculated increases with respect to cosmic rays
      are a factor 70 and 500 respectively for 29 September 1989 and 23 February 1956.
      The levels of radiation for high latitude, subsonic routes are calculated, using
      London to Los Angeles as an example, and can exceed 1 mSv, which is significantly
      higher than for Concorde routes from Europe to New York. The sensitivity of the
      calculations to spectral fitting, geomagnetic activity and other assumptions
      demonstrates the requirement for widespread carriage of radiation monitors on
      aircraft.

PMID- 14727668
TI  - The limitations of using vertical cutoff rigidities determined from the IGRF
      magnetic field models for computing aircraft radiation dose.
AB  - Vertical cutoff rigidities derived from the International Geomagnetic Reference
      Fields (IGRF) are normally used to compute the radiation dose at a specific
      location and to organize the radiation dose measurements acquired at aircraft
      altitudes. This paper presents some of the usually ignored limits on the accuracy
      of the vertical cutoff rigidity models and describes some of the computational
      artifacts present in these models. It is noted that recent aircraft surveys of
      the radiation dose experienced along specific flight paths is sufficiently
      precise that the secular variation of the geomagnetic field is observable.

PMID- 14727669
TI  - The space-developed dynamic vertical cutoff rigidity model and its applicability
      to aircraft radiation dose.
AB  - We have developed a dynamic geomagnetic vertical cutoff rigidity model that
      predicts the energetic charged particle transmission through the magnetosphere.
      Initially developed for space applications, we demonstrate the applicability of
      this library of cutoff rigidity models for computing aircraft radiation dose. The
      world grids of vertical cutoff rigidities were obtained by particle trajectory
      tracing in a magnetospheric model. This reference set of world grids of vertical
      cutoff rigidities calculated for satellite altitudes covers all magnetic activity
      levels from super quiet to extremely disturbed (i.e., Kp indices ranging from 0
      to 9+) for every three hours in universal time. We utilize the McIlwain "L"
      parameter as the basis of the interpolation technique to reduce these initial
      satellite altitude vertical cutoff rigidities to cutoff rigidity values at
      aircraft altitudes.

PMID- 14727670
TI  - The local time dependence of the anisotropic solar cosmic ray flux.
AB  - The distribution of the solar cosmic radiation flux over the earth is not
      uniform, but the result of complex phenomena involving the interplanetary
      magnetic field, the geomagnetic field and latitude and longitude of locations on
      the earth. The latitude effect relates to the geomagnetic shield; the longitude
      effect relates to local time. For anisotropic solar cosmic ray events the maximum
      particle flux is always along the interplanetary magnetic field direction,
      sometimes called the Archimedean spiral path from the sun to the earth. During
      anisotropic solar cosmic ray event, the locations on the earth viewing "sunward"
      into the interplanetary magnetic field direction will observe the largest flux
      (when adjustments are made for the magnetic latitude effect). To relate this
      phenomena to aircraft routes, for anisotropic solar cosmic ray events that occur
      during "normal quiescent" conditions, the maximum solar cosmic ray flux (and
      corresponding solar particle radiation dose) will be observed in the dawn
      quadrant, ideally at about 06 hours local time.

PMID- 14727671
TI  - Commentary. Relationships between serum lipids and subsequent mortality in an
      insured population.

PMID- 14727672
TI  - An introduction to the politics of science: culture, race, ethnicity, and the
      Supplement to the Surgeon General's Report on Mental Health.

PMID- 14727673
TI  - Commentary: message from the 16th U.S. Surgeon General.

PMID- 14727674
TI  - Commentary: making culture count in mental health reports from the Surgeon
      General.

PMID- 14727675
TI  - Commentary. The measure of a people can be found in their willingness to consider
      refinements.

PMID- 14727676
TI  - Extending the boundaries, bridging the gaps: crafting Mental Health: Culture,
      Race, and Ethnicity, a Supplement to the Surgeon General's Report on Mental
      Health.
AB  - The August 2001 issuance of Mental Health: Culture, Race, and Ethnicity--A
      Supplement to Mental Health: A Report of the Surgeon General, represents a
      landmark in the dialogue--political and scientific--regarding health disparities
      in the United States. This paper offers a critical appraisal of the process and
      structure of generating these reports, paying particular attention to issues that
      marked serious epistemological tensions among the participants. These issues
      revolved around the relative emphasis placed on (1) mental illness and mental
      health; (2) risk, etiology, and treatment versus prevention and promotion; (3)
      large-scale, population-based surveys and randomized clinical trials as the
      standard bearers of scientific evidence; (4) variation related to gender, social
      class, and culture; (5) ethnicity and culture as dispositional variables or
      individual glosses as opposed to dynamic, collective phenomena; and (6) the
      historical forces that shaped the contemporary context for much of this
      discussion. It describes the sometimes subtle, other times stark differences in
      assumptions and experience that sprang from disciplinary orientations,
      investigative methods, institutional affiliations, and personal histories and
      agendas.

PMID- 14727677
TI  - Challenges to consensus in preparing the Supplement to the Surgeon General's
      Report on Mental Health.
AB  - Preparing the Supplement to the Surgeon General's Report on Mental Health proved
      controversial because the assignment, by its nature, challenged several forms of
      consensus that typically remain unexamined. They included disciplinary
      assumptions about theory and methods, sociopolitical assumptions about the
      relevance of history to contemporary circumstances of ethnic minority groups in
      America, the rigor and usefulness of cultural formulation, and whether the burden
      of proof rested with those who took for granted that sociocultural differences
      exist in theories of behavior, or those who took for granted the existence of
      universals. Preparation of the Supplement illustrates the uncertainty and tension
      that arise when unexamined boundaries and perspectives lose their capacity to
      serve as guides to scientific judgment and discourse.

PMID- 14727678
TI  - Reflections on the Surgeon General's Report on Mental Health, Culture, Race, and
      Ethnicity.
AB  - The main goal of this paper is to evaluate the Supplement to the Surgeon
      General's Report on Mental Health, with an eye toward informing future efforts to
      prevent and treat mental illness among racial and ethnic minorities. I first
      briefly discuss the historical background of the Supplement. I then present its
      strengths, which include the authority and visibility of the Office of the
      Surgeon General, the organization of the report by racial/ethnic group, the
      examination of the social and historical context of each of the racial/ethnic
      groups, and the emphasis on science. Last, I identify three major tensions within
      the Supplement, focusing on groups versus cultural processes, situating culture
      within individuals or social worlds, and examining differences between minority
      groups and whites versus examining conceptually informed processes. The
      Supplement makes a significant contribution to advancing our understanding of the
      mental health of racial and ethnic minority groups. The actions that follow (or
      don't follow), however, will determine the import of this document.

PMID- 14727679
TI  - What to do with race? Changing notions of race in the social sciences.
AB  - The Supplement to the Surgeon General's Report on Mental Health documents that
      race, ethnicity, and culture are linked to the use of mental health services and
      the receipt of quality mental health care. The Supplement provides an elaborate
      discussion on how culture affects mental health care without a corresponding
      level of discourse on race. How race is handled in the Supplement suggests that
      it is still a sensitive topic and one that is difficult to address in a public
      report. This sensitivity parallels the difficulties that the social sciences have
      had in investigating issues of race. In this paper, we highlight some
      perspectives that have influenced the way race has been studied in the past and
      how these views reflect the general political climates of the eras that produced
      them.

PMID- 14727680
TI  - The mental health of ethnic minority groups: challenges posed by the Supplement
      to the Surgeon General's Report on Mental Health.
AB  - In contrast to the conclusions reached by the Supplement to the Surgeon General's
      report on mental health, there is evidence that the various ethnic minority
      groups may exhibit significant differences in the prevalence of mental disorder.
      These differences cannot be fully explained by disparities or inequities in
      mental health services. African Americans appear to have relatively low
      prevalence rates despite a history of prejudice, discrimination, and the
      resulting stress. Ethnic differences are also revealed by findings that
      acculturation is negatively related to mental health for Mexican Americans and
      positively related to mental health for Asian Americans. Implications of these
      findings are discussed.

PMID- 14727681
TI  - Including ethnic minorities in mental health intervention research: a practical
      approach to a long-standing problem.
AB  - This paper examines a controversy that arose while developing a supplement to
      Mental Health: A Report of the Surgeon General that was focused on ethnic
      minority mental health. The controversy involved whether and how to make
      recommendations about ethnic minorities seeking mental health care. We found that
      few studies provided information on outcomes of mental health care for ethnic
      minorities. In this paper, we discuss outcomes of mental health care for ethnic
      minorities and how to proceed in developing an evidence base for understanding
      mental health care and minorities. We conclude that entering representative
      (based on population) numbers of ethnic minorities in efficacy trials is unlikely
      to produce useful information on outcomes of care because the numbers will be too
      small to produce reliable findings. We also conclude that while conducting
      randomized efficacy trials for all mental health interventions for each ethnic
      group would be impractical, innovative and theoretically informed studies that
      focus on specific cultural groups are needed to advance the knowledge base. We
      call for theory-driven research focused on mental health disparities that has the
      potential for understanding disparities and improving outcomes for ethnic
      minority populations.

PMID- 14727682
TI  - The quality of mental health care for African Americans.
AB  - In response to the Surgeon General's request for more research on racial
      disparities in mental health care, especially research that includes high-need
      populations (e.g., the homeless, incarcerated, children in foster care, and
      substance abusers), we examined racial disparities in the provision of mental
      health counseling, psychotherapy, and pharmacotherapy in hospital outpatient
      settings using nationally representative data from the 1997 National Hospital
      Ambulatory Medical Care Survey (NHAMCS). After controlling for diagnosis and
      other factors, we found that African Americans were less likely than whites to
      receive mental health counseling and psychotherapy, but more likely than whites
      to receive pharmacotherapy. We also found that substance abuse clinics were more
      likely than primary care and specialty mental health clinics to provide mental
      health counseling and psychotherapy. However, specialty mental health clinics
      were the only clinics to provide pharmacotherapy. Future research should examine
      racial disparities in a variety of settings, controlling for diagnosis as well as
      other factors.

PMID- 14727683
TI  - Addendum: a brief commentary on the making of the Supplement to the Surgeon
      General's Report on Mental Health.

PMID- 14727684
TI  - Helicobacter pylori and gastric diseases.
AB  - Helicobacter pylori (H. pylori) infection is a pathogenic agent of gastric
      diseases, but their mechanisms are unclear. Effects of ammonia, tumor necrosis
      factor (TNF), and anti-Lewis autoantibodies induced after H. pylori infection on
      the development of gastric diseases were investigated. Ammonia disturbed the
      collagen metabolism in the ulcer base. Soluble TNF receptors regulate the action
      of TNF. The involvement of anti-Lewis autoantibodies in the development of peptic
      ulcer might be unlikely. Moreover, H. pylori-specific IgA in gastric juice and
      TNFalpha gene polymorphism in persons infected with H. pylori were studied.
      According to H. pylori-specific IgA titer in gastric juice, persons were divided
      into two histologically and endoscopically different states of disease. TNFA -857
      single nucleotide polymorphism (SNP) may be associated with rugal hyperplastic
      gastritis and gastric carcinomas without severe atrophy. However, complete
      elucidation of pathogenic mechanisms of H. pylori-induced gastric diseases
      requires further research.

PMID- 14727685
TI  - Transgenic rat models of vasopressin overexpression.
AB  - Vasopressin has an important role in water metabolism and its impairment induces
      some clinical disorders such as diabetes insipidus or syndrome of inappropriate
      antidiuresis (SIAD). SIAD is caused by the overproduction of vasopressin which
      induces diluting hyponatremia. The accurate diagnosis and appropriate therapy
      have not settled up to date because its pathophysiology is very complicated. It
      is meaningful to develop a rat model of SIAD in which human vasopressin gene is
      overexpressed in order to analyze pathophysiological changes. Several models
      transgenic for vasopressin including us had been generated. The transgenic rats
      provide a useful model to investigate various pathophysiological changes
      resulting from the oversecretion of vasopressin. Some interesting results based
      on these animal models are reviewed.

PMID- 14727686
TI  - Small-for-size graft in liver transplantation.
AB  - Controversies on small-for-size (SFS) graft in liver transplantation have evolved
      in parallel with the history of living donor liver transplantation for adults. It
      is true that the liver regenerates rapidly within a limited threshold. But
      'normal' liver weight itself is variable and the influences of variable liver
      graft and extrahepatic factors are not negligible in pathological condition.
      Clinical features of 'SFS syndrome' are neither specific nor inevitable in low
      weight liver and many other factors than actual graft weight contribute to their
      occurrence. Among them, early elevation of portal venous pressure highly probably
      plays a key role. In the clinical trials of surgical modification and local
      pharmacological manipulation targeting portal hemodynamics and tissue congestion,
      it may be the time to discard an excessive fear for SFS grafts and to minimize
      unnecessary withdrawal from the opportunity of transplantation.

PMID- 14727687
TI  - Persistent Helicobacter pylori infection and genetic polymorphisms of the host.
AB  - Helicobacter pylori (HP) infection elevates the risk of gastric diseases
      including peptic ulcer and gastric cancer. The infection induces inflammatory
      cytokines, which could work both for and against lifetime infection in the human
      stomach. Genetic polymorphisms of the cytokines and other related ligands,
      receptors, and enzymes may influence persistent HP infection. This paper
      summarizes studies done on the associations between anti-HP antibody
      seropositivity and polymorphism genotypes. To date, the associations with the
      polymorphisms of fucosyl transferase 2 (FUT2 or secretor gene), FUT3 (Lewis
      gene), interleukin 1A (IL-1A), IL-1B, IL-1RN, IL-8, IL-10, myeloperoxidase (MPO),
      and tumor necrosis factor A (TNF-A) and TNF-B have been reported. Polymorphisms
      of other related genes, CD14, CXC chemokine receptor 2 (CXCR2), IL-1RI, nuclear
      factor KB2 (NF-KB2), and Toll-like receptor 4 (TLR4), have the potential to
      influence persistent infection. Unpublished results from our datasets are
      reported here for all these polymorphisms except TLR4. Gene-environment
      interactions between these genotypes and smoking are reviewed. An effect on OR
      due to the involvement of unexposed subjects is demonstrated to elucidate a
      disadvantage in the studies done in areas where the majority of the population is
      not exposed to HP.

PMID- 14727688
TI  - Radiation therapy for metastatic brain tumors from lung cancer--a review to
      devise individualized treatment plans.
AB  - We retrospectively analyzed patients with brain metastasis from lung cancer to
      evaluate treatment modalities for metastatic brain tumors and to devise criteria
      for individualized treatment plans. Between October, 1986 and December, 1994, 90
      patients were selected for this study. The majority (67.8%) received whole-brain
      radiotherapy (WBRT) alone. WBRT following surgical removal was carried out on 14
      patients (15.5%). The median dose of radiation therapy was 43.3 Gy for WBRT. The
      results were as follows: (1) PS (1 and 2 vs. 3 and 4), which showed a significant
      difference (p < 0.0001) in survival by both univariate analysis and multivariate
      analysis, (2) brain metastasis alone or concurrent metastases to other sites (p =
      0.0001) by univariate analysis, (3) the primary lesion controlled or uncontrolled
      (p = 0.0006) by univariate analysis, (4) solitary brain metastasis or multiple
      brain metastases (p = 0.0145) by univariate analysis. Patients were classified
      into 3 groups, A (PS1, 2, the primary lesion controlled, no distant metastasis
      and solitary brain metastasis), B (others except for groups A and C), and C (PS
      3,4) based on 4 significant factors. The 1-year survival rates and median
      survival times were, respectively 75% and 1,767 days in Group A, 40.6% and 313
      days in Group B, and 7.8% and 121 days in Group C (p < 0.0001). Although the
      possibility of individualized treatment was suggested, based on 4 factors
      associated with the patient's condition and disease progression before treatment
      for brain metastasis, further evaluation by randomized clinical trials is needed.

PMID- 14727689
TI  - Cell death of human oral squamous cell carcinoma cell line induced by herpes
      simplex virus thymidine kinase gene and ganciclovir.
AB  - Suicide gene therapy combining herpes simplex virus thymidine kinase gene (HSVtk)
      and ganciclovir (GCV) is one strategy for the treatment of head and neck squamous
      cell carcinoma (HNSCC). The purpose of this study is to determine the mechanism
      of cell death that occurs in suicide gene therapy using HSVtk and GCV and to
      assess the safety of that therapy. The human oral squamous cell carcinoma cell
      line SAS was treated with adenovirus vector containing HSVtk gene (AdHSVtk) and
      GCV in vitro. Morphological changes including chromatin condensation, cell
      shrinkage, blebbing of cell membrane, and ballooning formations were observed.
      Changes in the localization of phospholipids in the cell membrane were also
      observed. The results of flow cytometry showed a maximum of about 65% of cells in
      the early phase of apoptosis. In addition, DNA fragmentation was investigated
      using the TUNEL method in vivo. Nude mice (BALB/c AJD(-nu-), aged 4 weeks) were
      implanted with SAS and treated with AdHSVtk and GCV. Tumor sections were then
      observed. The treatment group was confirmed to have DNA fragmentation-positive
      cells. These results suggest that suicide gene therapy using AdHSVtk and GCV led
      to apoptosis of the oral squamous cell carcinoma cell line.

PMID- 14727690
TI  - Cultural identity and mental health.

PMID- 14727691
TI  - Inception rates of deliberate self-harm among adolescents in West London.
AB  - BACKGROUND: Studies have suggested that inception rates of deliberate self-harm
      among different ethnic group adolescents are broadly similar. AIMS: We set out to
      study the rates of adolescent self-harm over a calendar year in Ealing--part of
      West London. METHODS: All cases of deliberate self-harm presenting to the A&E
      department and paediatrics were identified and socio-cultural factors studied.
      Ethnicity was obtained using self-ascription. RESULTS: A total of 76 cases were
      identified over one year. Using the at risk population as denominator, no
      differences in inception rates were noted according to ethnicity. Overdoses were
      the commonest method used for deliberate self-harm. CONCLUSIONS: The similarities
      between the Asian and white adolescents suggest that some common aetiological
      factors may be at play. The risk factors may be related to gender rather than
      ethnicity in this age group.

PMID- 14727692
TI  - A welfare benefits outreach project to users of community mental health services.
AB  - BACKGROUND: Many psychiatric service users are entitled to welfare benefits, but
      work from the UK and the USA suggests many are either unaware of their
      entitlements or find the benefits system difficult to access. AIMS: This study
      has four aims: 1) to assess the extent to which people using a range of community
      mental health services receive the welfare benefits to which they are entitled;
      2) to calculate the impact on income of receiving help from specialist benefits
      advisors; 3) to ascertain sociodemographic risk factors for under-claiming; and
      4) to identify reasons for under-claiming related to the claims system itself, in
      order to make recommendations for routine practice. METHODS: This report makes
      use of data collected during a welfare benefit uptake project by Mind in Croydon
      staff (MF-G, RO, RP). Benefit assessments were offered to a total of 153 people
      attending any Croydon resource centre (run by the Health Service) other than the
      pilot site, or day centre (run by Social Services) for people with mental health
      problems. All those who were identified as under-claiming were offered help
      pursuing claims through to conclusion. We used quantitative methods to address
      the first three aims; qualitative methods in the form of case studies were used
      to address the fourth. RESULTS: One-third (34%) of people seen were getting their
      correct entitlement and two-thirds (66%) were under-claiming. All those found to
      be under-claiming who accepted all the help offered (87 out of 99 underclaimants)
      did gain additional benefits as a result, of a mean annual amount of pound 3079
      each. Under-claiming was more frequent in those under 65 years of age, but having
      had previous advice or having a care manager did not protect against under
      claiming. A number of reasons for under-claiming were identified. CONCLUSIONS:
      For a large and possibly increasing proportion of people using community mental
      health services, the current benefits system necessitates frequent advice and
      help by expert advisers to avoid poverty due to underclaiming. The adverse
      effects on quality of life and mental health may be significant, as are the
      economic implications of correcting this level of under-claiming.

PMID- 14727693
TI  - War, exile, moral knowledge and the limits of psychiatric understanding: a
      clinical case study of a Bosnian refugee in London.
AB  - BACKGROUND: This paper describes a Bosnian refugee, a survivor of war and ethnic
      cleansing, during a 3-year follow-up in a psychiatry clinic. DISCUSSION: This
      case throws light on the tension between medicotherapeutic and sociomoral ways of
      understanding the effects of such experiences, and of the limitations of morally
      and politically neutral psychiatric categories and technologies. Suffering always
      invokes questions of values: in this case the clinical picture represented a
      moral protest at what had been done with such impunity, and a refusal to
      accommodate to a world which now seemed unintelligible. The clinical picture also
      embodied the collective outrage, and sense of unfinished business, which many
      back in Bosnia itself were carrying in the wake of the 1995 Dayton peace accords
      which effectively legitimised the lines of ethnic cleansing. CONCLUSIONS: DSM or
      ICD diagnoses of depressive disorder or post-traumatic stress disorder turned out
      to lack validity and explanatory power. Claims that victims of war and atrocity
      typically have an unmet need for mental health services are overstated. Recovery
      from the effects of war may depend on reestablishing a sense of intelligibility,
      a task that must primarily go on in social space rather than mental space.

PMID- 14727695
TI  - A comparison of lay-beliefs about autism and obsessive-compulsive disorder.
AB  - The purpose of the two studies was to compare lay beliefs regarding the aetiology
      and treatment of autism (study 1) and obsessive-compulsive disorder (OCD) (study
      2). It was hypothesised that beliefs about autism would be based primarily on a
      biomedical theory while beliefs regarding OCD primarily on psychological notions
      of cause and cure. Parents' interviews were conducted in study 1 and revealed
      that, as hypothesised, parents hold predominantly biomedical views about autism.
      Participants (n = 92) completed both questionnaires that involved rating a range
      of theories of aetiology and treatment approaches for each disorder. Statistical
      analysis confirmed that lay beliefs about autism were primarily biomedical and
      beliefs about OCD were primarily psychological. Multiple regression analyses
      indicated that a range of individual difference factors (religiousness, interest
      in mental illness, age and knowledge of autism) predicted beliefs about the
      importance of some of the five factors derived from factor analysis of belief
      statements. The relevance of investigating lay beliefs of aetiology and treatment
      of psychiatric disorders for clinical practice is also highlighted.

PMID- 14727694
TI  - Measuring community mental health in developing societies: evaluation of a
      checklist format in Nepal.
AB  - BACKGROUND: There is growing recognition of the importance of mental health
      problems in developing countries. In large part, however, we have very limited
      epidemiological data at national and/or community levels about the prevalence of
      mental illnesses. AIMS: The purpose of this paper is to describe the reliability
      and validity characteristics of an assessment tool that may be useful for
      conducting community-level surveys (particularly in rural communities of
      developing countries) to obtain prevalence rates of mental illnesses. METHODS: We
      used a sample of adults residing in a rural village in Nepal to assess disorders
      with a modified version of the DSM-III-R Checklist. We evaluated construct
      validity, scale reliability, convergent validity and discriminant validity.
      RESULTS: There is strong evidence for the construct validity of generalized
      anxiety and depression in our sample. By contrast, the symptoms associated with
      mania and schizophrenia were not empirically distinct. Convergent validity is
      acceptable. As a test of validity characteristics, the pattern of
      sociodemographic correlations suggests that the specific social origins of
      disorder in Nepal will require further investigation. CONCLUSION: The first step
      in obtaining high quality information on the distribution of mental illness in
      developing countries is to establish some reliable and valid indicators of
      disorder. The checklist format for assessing disorder appears to meet this
      objective and offers the possibility that community-level prevalence studies can
      be reasonably conducted.

PMID- 14727696
TI  - Use of qualitative research methods in general medicine and psychiatry:
      publication trends in medical journals 1990-2000.

PMID- 14727697
TI  - Prosthetic prescription in the Netherlands: an observational study.
AB  - Prosthetic prescription for lower limb amputees and the methodology used are
      primarily based on empirical knowledge. Clinical expertise plays an important
      role that can lead to an adequate prescription; however, a clear evidence based
      motivation for the choices made cannot be given. This can lead to local
      prescription variations with regard to overuse or underuse of prosthetic care and
      a lack of transparency for consumers and health insurance companies. Hence a
      clinical guideline may lead to a more consistent and efficient clinical practice
      and thus more uniformly high quality care. The purpose of this study was to get
      insight into potential similarities in prescription criteria in clinical practice
      in the Netherlands. Secondly, the authors were interested to know if prosthetic
      prescription was primarily based on the level of activity or intended use of the
      prosthesis. As part of the development of a consensus-based clinical guideline a
      multi-centred, cross-sectional study was carried out in order to observe the
      prosthetic prescription for a group of lower limb amputees. Therefore
      prescription data were collected from 151 amputees with trans-femoral amputation,
      knee disarticulation or trans-tibial amputation. Results of the multiple logistic
      regression show no relationship between the activity level and any of the
      variables included in the equation such as the hospital or medical doctor in
      Physical and Rehabilitation Medicine (MD in P&RM), prosthetic components, age of
      the amputee or reason of amputation. The criteria used are merely based on the
      clinical expertise and local experience whereas the actual prescriptions differ
      from location to location. In conclusion the development of a clinical guideline
      for prosthetic prescription in lower limb amputation is recommended. The
      information gained from this observational study will be used in a clinical
      guideline procedure for prosthetic prescription in the Netherlands.

PMID- 14727698
TI  - Lower limb proximal amputation for a tumour: a retrospective study of 12
      patients.
AB  - OBJECTIVE: To analyse survival, prosthetic fitting and functional status after
      trans-femoral amputation or hip disarticulation for a primitive tumour. METHODS:
      Retrospective study of all patients admitted since 1985. RESULTS: Mean age at
      amputation was 55. Causes of amputation were osteosarcoma in 50%. Eight (8)
      patients had initial conservative surgery. Local recurrence was never observed.
      Nine (9) developed metastasis and required further hospitalisation. Fifty percent
      (50%) of patients died. Inpatient rehabilitation started 14 days after amputation
      (7-27), and was of a mean duration of 32 days. Prosthetic fitting was performed
      13 days after admission (7 days when a liner was used). Further improvement of
      the prosthesis was performed in 10 patients. Among the patients who died, 5 had
      gone home, 4 were wearing their prosthesis all day long and 2 walked indoors with
      no additional support at discharge. Three (3) patients lived less than 2 months
      at home. Among the patients who did survive, all went home, 5 were wearing their
      prosthesis all day long and 2 walked indoors without aid at discharge. Two (2)
      patients practised sport and 4 drove. All the patients who were active have gone
      back to work. CONCLUSIONS: Gain due to prosthesis provision is undebatable. Good
      functional results can be obtained with adapted materials. Initial problems due
      to the synchronisation of treatments are resolved with multidisciplinary care.
      All patients should have a rapid and short hospitalisation in a rehabilitation
      unit and receive a first, simple prosthesis that can be further adapted.

PMID- 14727699
TI  - Mobility outcome following unilateral lower limb amputation.
AB  - This study investigated mobility outcome following unilateral trans-tibial or
      trans-femoral amputation. It was an observational study at the sub-regional
      amputee rehabilitation centre in Sheffield, UK. All unilateral trans-tibial or
      transfemoral amputees referred during the study period were included. The Harold
      Wood Stanmore mobility grade was recorded approximately one year following
      initial assessment at the centre. Of the 357 amputees referred, complete outcome
      data was available for 281 (78.7%). The mean age was 68 years (range 16-95),
      70.1% were male, and the aetiology of the amputation was vascular or diabetic in
      87.5% of cases. Trans-tibial amputations accounted for 50.5% and trans-femoral
      49.5%. Almost all trans-tibial and trans-femoral amputees aged 50 and under
      achieved functional household and community mobility. Approximately 50% of the
      trans-tibial amputees aged over 50 years gained independent community mobility
      and around 60% household mobility. There was a significant worsening of community
      mobility rates with increasing age but for household mobility the differences did
      not reach statistical significance. Fewer than 25% of trans-femoral amputees aged
      over 50 achieved community mobility and around 50% achieved household mobility.
      There was a statistically significant deterioration in both community and
      household mobility levels with increasing age. This study concludes that mobility
      rates one year after prosthetic provision for unilateral trans-tibial and trans
      femoral amputees worsen with increasing age at amputation and a higher level of
      amputation.

PMID- 14727700
TI  - Development and measurement properties of the Orthotics and Prosthetics Users'
      Survey (OPUS): a comprehensive set of clinical outcome instruments.
AB  - The need to measure and evaluate orthotics and prosthetics (O&P) practice has
      received growing recognition in the past several years. Reliable and valid self
      report instruments are needed that can help facilities evaluate patient outcomes.
      The objective of this project was to develop a set of self-report instruments
      that assess functional status, quality of life, and satisfaction with devices and
      services that can be used in an orthotics and prosthetics clinic. Selecting items
      from a variety of existing instruments, the authors developed and revised four
      instruments that differentiate patients with varying levels of lower limb
      function, quality of life, and satisfaction with devices and services. Evidence
      of construct validity is provided by hierarchies of item difficulty that are
      consistent with clinical experience. For example, with the lower limb function
      instrument, running one block was much more difficult than walking indoors. The
      instruments demonstrate adequate internal consistency (0.88 for lower limb
      function, 0.88 for quality of life, 0.74 for service satisfaction, 0.78 for
      device satisfaction). The next steps in their research programme are to evaluate
      sensitivity and construct validity. The Orthotics and Prosthetics Users' Survey
      (OPUS) is a promising self-report instrument which may, with further development,
      allow orthotic and prosthetic practitioners to evaluate the quality and
      effectiveness of their services as required by accreditation standards such as
      those of the American Board for Certification in Orthotics and Prosthetics that
      mandate quality assessment.

PMID- 14727701
TI  - Measurement of the consistency of patellar-tendon-bearing cast rectification.
AB  - The quality of fit of a trans-tibial patellar-tendon-bearing (PTB) socket may be
      influenced by consistency in casting, rectification or alignment. This paper
      quantifies, for the first time, the variations in the rectified casts between two
      experienced prosthetists and the variation between the rectified casts of each
      individual prosthetist. Prosthetists A and B observed the hand casting of a
      typical trans-tibial amputee. Each prosthetist was supplied with 5 previously
      measured duplicated plaster models. The two prosthetists rectified the supplied
      plaster models based on their own interpretation of basic rectification
      guidelines. Both prosthetists operated in isolation. The re-measured rectified
      plaster model data was compared with the unrectified data. The extent of
      rectification at each of 1800 locations per plaster model was calculated. In
      zones of major rectification, the mean difference between prosthetists was
      quantified as 2mm and the standard deviation (SD) about that mean was +/- 1mm for
      each prosthetist. The co-ordinates of the apex of the fibular head for the 10
      modified casts indicated that the maximum variation was in the axial direction
      with a SD of 4.3mm for prosthetist A and a SD of 2.8mm for prosthetist B. The
      lengths of the 5 plaster models rectified by prosthetist A indicated a SD of
      0.2mm whereas the lengths of the 5 plaster models rectified by prosthetist B
      indicated a SD of 2.9mm.

PMID- 14727702
TI  - Dynamic balance training during standing in people with trans-tibial amputation:
      a pilot study.
AB  - Falls and fear of falling are significant problems arising from impaired
      balancing abilities that affect people with lower limb amputation during
      unassisted transfer manoeuvres and ambulation. It is important to develop and
      evaluate efficient therapeutic interventions aimed at improving balancing and
      coordination skills. A group of 14 persons after trans-tibial amputation, fitted
      with trans-tibial prostheses, were included in a balance-training programme,
      consisting of approximately 20 minutes of balance training per day for five
      consecutive days on BalanceReTrainer--a novel balance-training, fall-safe
      mechanical apparatus. Before and after the training period three outcome measures
      were taken: duration of standing only on the prosthetic leg, timed up and go test
      and 10m walk. Each measurement was repeated five times and the mean value was
      used in the subsequent calculation of mean values and standard deviations for the
      group. Before training the group was able to stand on the prosthetic leg for 2.98
      +/- 2.75s, they needed 6.15 +/- 1.9s for accomplishing timed up and go test and
      they needed 5.51 +/- 1.5s to cover the distance of 10m. After the treatment
      period the values were 4.3 + 4.5s, 5.4 +/- 1.5s and 4.5 +/- 0.9s, respectively.
      The results indicate improved performance in all three measured tasks, thereby
      indicating that the applied treatment programme improves balancing and ambulation
      abilities in people after trans-tibial amputation.

PMID- 14727703
TI  - Early trans-tibial oedema control using polymer gel socks.
AB  - The aim of this investigation was to determine if early trans-tibial oedema
      control, by polymer gel socks prior to the fitting of a shrinker, could enhance
      trans-tibial stump volume reduction. Sixteen (16) adults, following unilateral
      trans-tibial amputation, were randomly allocated into 2 groups and baseline
      volume measurements taken of their stumps. The control group followed the normal
      removable rigid dressing programme, while the experimental group wore a polymer
      gel sock in conjunction with the removable rigid dressing. When wound healing
      permitted fitting of a shrinker, use of the polymer sock was discontinued and a
      stump volume measurement was taken. The shrinker was worn for a minimum of 2 days
      before casting for a prosthesis and a final stump volume measurement taken.
      Volumes were measured by water filling casts taken of the stump and calculated as
      a percentage of the baseline volume and the rate of volume reduction calculated.
      Two t-tests for unequal variance (2-tail, alpha=0.05) were used to compare the
      rate of percentage volume reduction between the groups, for the trial period of
      baseline to shrinker fitting and baseline to casting. A statistical difference
      was observed for the period of baseline to shrinker exceeding the 95% confidence
      limit (p<0.05). No significant difference was detected for the overall period of
      baseline to cast. It was concluded that early oedema control by polymer gel sock
      could enhance stump volume reduction, prior to a shrinker. It was also found that
      no volume advantage was carried over to the time of casting for a prosthesis.

PMID- 14727704
TI  - Pelvic motion in trans-femoral amputees in the frontal and transverse plane
      before and after special gait re-education.
AB  - Using a special gait re-education programme, combining methods in physiotherapy
      with a psychological therapeutic approach to integrate the prosthesis with normal
      movements and to increase body awareness, the authors studied unilateral trans
      femoral amputees aged 16-60 years with trauma or tumour as causes. In their
      service area they found 16 such current prosthetic users with at least 2 years of
      prosthetic experience and 9 who could complete the programme. Gait was measured
      before and after treatment and at 6 months follow-up with a three-dimensional
      motion analysis system and was compared to a reference group of 18 healthy
      volunteers of similar age. Results showed normalised gait speed and increased
      symmetry in step length after treatment, but reduced symmetry in pelvic motion.
      The reference group had a pelvic rotation of + 4 degrees both in the frontal and
      transverse planes. In the frontal plane, pelvic obliquity increased after
      treatment to a similar amplitude to the reference group, but with a different
      timing. Pelvic internal rotation on the amputated side increased to about 8
      degrees in the beginning of stance. The amputated and the intact side before
      treatment were more symmetrical than afterwards and also when compared with the
      reference group. In spite of this, gait appeared to be more symmetrical, probably
      due to more efficient pelvic motion and more symmetrical upper-body movements.
      This was probably an effect of increased work with the intact side to compensate
      for the lack of power on the amputated side. These results remained at follow-up.

PMID- 14727705
TI  - Dokuz Eylul University (DEU) orthosis: an orthotic method of preventing ankle
      equinus during tibial lengthening.
AB  - An orthosis developed in Dokuz Eylul University (DEU) at the School of Physical
      Therapy and Rehabilitation, Department of Orthotics and Prostheticsis is
      described. It is applied as a non-invasive device attached to the distal ring of
      the Ilizarov external fixator to keep the ankle joint in a neutral position and
      prevent ankle equinus during tibial lengthening with Ilizarov technique. This
      minimises additional invasive techniques such as heel cord release and
      prophylactic pinning of the heel and the foot, and manipulation under
      anaesthesia. It may also be detached by the physiotherapist or patient when
      physical therapy is needed during the lengthening procedure.

PMID- 14727706
TI  - Critical review on non-operative management of adolescent idiopathic scoliosis.
AB  - There are a number of different non-operative interventions which aim to control
      moderate adolescent idiopathic scoliosis (AIS) from progression. Clinicians may
      find difficulties in the selection of appropriate interventions for AIS. A
      comprehensive literature review was carried out to study all contemporary non
      operative interventions, it was noted that rigid spinal orthoses apparently give
      more curve control; however, it would compromise the patient's quality of life
      via those inevitable factors--physical constraint, poor acceptance and
      psychological disturbance. There is a trend to develop more effective, acceptable
      and user-friendly interventions. Under such an aspiration, the theories and
      clinical evidence of different interventions should be developed along the
      clinical pathway of early intervention with reliable indicators/predictors,
      patient's active participation, dynamic control mechanism, holistic psychological
      and psychosocial considerations, and effective and long-lasting outcome.

PMID- 14727707
TI  - Coordinated single unlocking mechanism for a double joint mechanism in a trans
      femoral prosthesis for an amputee with a short stump.
AB  - A double joint design with sequential unlocking mechanism is described. This
      mechanism enables the patients to sit upon regular chairs without the fear of
      prosthetic displacement.

PMID- 14727708
TI  - Determinants of health status and the influence of primary health care services
      in Latin America, 1990-98.
AB  - Primary health care (PHC) services have been advocated as a means by which less
      developed countries may improve the health of their populations even in the face
      of poverty, low levels of literacy, poor nutrition and other factors that
      negatively influence health status. Using aggregated data from the World Bank and
      UNICEF this study examined which factors, both within the health care system and
      outside of it, are associated with under-5 mortality rates in 22 countries of
      Latin America and the Caribbean during the 1990s. In a multivariate analysis
      using generalized estimating equations for repeated measures, five factors were
      found to be independent predictors of lower under-5 mortality rates (U5MRs).
      These were vaccination levels, female literacy, the use of oral rehydration
      therapy, access to safe water and GNP per capita. When the magnitude of these
      associations were assessed, higher levels of GNP per capita was found to be very
      weakly associated with lower U5MRs, compared with female literacy and vaccination
      rates. These findings suggest that government policies which focus only on
      promoting economic growth, while not making important investments in PHC
      services, female education and access to safe water are unlikely to see large
      improvements in health status.

PMID- 14727709
TI  - Analysing the primacy of distance in the utilization of health services in the
      Ahafo-Ano South district, Ghana.
AB  - Although the distance factor has been identified as key in the utilization of
      health services in rural areas of developing countries, it has been analysed
      without recourse to related factors of travel time and transport cost. Also, the
      influence of distance on vulnerable groups in utilization has not been an object
      of survey by researchers. This paper addresses the impact of distance on
      utilization, and how distance compares with travel time and transport cost that
      are related to it in the utilization of health services in the Ahafo-Ano South
      (rural) district in Ghana. The study, a cross-sectional survey, also identifies
      the position of distance among other important factors of utilization. A sample
      of 400, drawn through systematic random technique, was used for the survey. Data
      were analysed using the regression model and some graphic techniques. The main
      instruments used in data collection were formal (face-by-face) interview and a
      questionnaire. The survey finds that distance is the most important factor that
      influences the utilization of health services in the Ahafo-Ano South district.
      Other key factors are income, service cost and education. The effect of travel
      time on utilization reflects that of distance and utilization. Recommendations to
      reduce distance coverage, improve formal education and reduce poverty have been
      made.

PMID- 14727710
TI  - Health policy and its implementation in small island developing states in the
      British West Indies.
AB  - Health policy and its implementation in small island developing states (SIDS) is
      a neglected area of study, and, seemingly, of little interest. The existing
      literature is generally characterized by descriptions of failure or incompetence,
      with little attempt to understand the nature and workings of the policy process
      in these small, yet complex, societies. The research undertaken in this article
      was carried out over 6 years in Anguilla (pop. 9000) and the British Virgin
      Islands (pop. 20 000), two British Overseas Territories in the North East
      Caribbean. The purpose of the research was to determine to what extent policy
      theory and the tools of policy analysis could be used to explain the nature and
      the outcomes of the health policy and implementation process. In trying to
      analyse and understand the policy process in these small islands it was necessary
      to understand their socio-politic character. In addition, the development of a
      model of the public policy and public administration system in the English
      speaking Caribbean was an essential part of this process. It was found that the
      conduct and outcome of the policy and implementation process in these islands
      varied significantly. It is postulated that the variations are anchored in the
      nature of the local context, the working practices and ideologies of politicians,
      senior public servants and the local policy elite.

PMID- 14727711
TI  - Working in a decentralized system: a threat to health workers' respect and
      survival in Uganda.
AB  - This article contributes to the sparse empirical material on the position of
      health workers within health sector reform. Using qualitative data gathered in
      1999, it shows how staff at rural health units in Tororo and Busia Districts
      experienced the reforms during the first 5 years of decentralization in Uganda.
      The analysis builds on a framework proposed by Franco et al. to examine the
      relation between health sector reform and health worker motivation. However, it
      diverges from their objective description of the factors determining motivation,
      giving more emphasis to the subjective perspective of the health workers. The
      categorical distinction between organizational and cultural/community factors was
      less relevant for them as actors. Two themes cross-cut their lives inside and
      outside the health facilities: professional identity, which entailed recognition
      by both the organization and members of the community; and 'survival strategies',
      which were necessitated by the desire to maintain a status and lifestyle
      befitting a professional. Reform weakened workers' positions as professionals and
      hindered facility-based 'survival strategies' that helped them get by on poor
      salaries. With an overall fall in remuneration, they were more motivated than
      ever to establish supplementary sources of income outside the formal government
      health care system.

PMID- 14727713
TI  - PITTCON 2004.

PMID- 14727712
TI  - The importance of quality, access and price to health care consumers in Bulgaria:
      a self-explicated approach.
AB  - One approach to the problem of low patient satisfaction in Bulgaria is to
      identify attributes of health care services that the consumers value most and to
      focus on their improvement. Based on data from a household survey, this paper
      examines the importance that health care consumers attach to quality, access and
      price. The survey was conducted in 2000 among the population of the region of
      Varna (the third largest city in Bulgaria). The elicitation of attribute
      importance was based on a self-explicated method. To analyse the data, an ordered
      logit regression was performed. The analysis shows that clinical quality is the
      most valued characteristic by Bulgarian health care consumers compared with
      social quality, access and price. Given the poor quality of health care provision
      in Bulgaria, the allocation of revenues to its improvement appears to be
      essential in order to raise patient satisfaction and to enhance social
      efficiency.

PMID- 14727714
TI  - Fourier transform infrared microscopic imaging: effects of estrogen and estrogen
      deficiency on fracture healing in rat femurs.
AB  - Infrared spectroscopic imaging with 6-10 microm spatial resolution was used to
      characterize the changes in fracture callus mineral content, carbonate content,
      mineral crystallinity, and collagen maturity in femurs of 3-month-old
      ovariectomized rats treated with estrogen (estrogen sufficiency) or vehicle
      (estrogen deficiency). Comparisons were also made in these animals to cortical
      bone at a distance from the callus. Analyses at 4, 8, and 12 weeks post fracture
      demonstrated that healing was accelerated in the estrogen-sufficient animals as
      demonstrated by increasing mineral content and collagen maturity and decreasing
      carbonate incorporation.

PMID- 14727715
TI  - Surface plasmon spectral fingerprinting of adsorbed magnesium phthalocyanine by
      angle and wavelength modulation.
AB  - A novel instrumental method for angle and wavelength modulated surface plasmon
      resonance (SPR) spectroscopy is applied to the problem of spectral selectivity in
      SPR experiments. For transparent analytes, SPR reflectivity data are reduced to a
      two-dimensional (2D) spectrum of resonance wavelength versus incident angle,
      lambdaSPR(theta). This spectrum encodes the refractive index (RI) dispersion of
      the analyte and illustrates the increased SPR spectral shift per unit RI change
      at longer wavelengths (lower angle). For the absorbing analyte magnesium
      phthalocyanine (MgPc), the 2D data reduction method is complicated by the way the
      SPR and MgPc-based spectral peaks mix. Fresnel reflectivity models support
      experimental observations of spectral branching and qualitative fingerprints in
      the form of branched spectra, and difference reflectivity deltaR(lambda, theta)
      contour plots are presented.

PMID- 14727716
TI  - Silver-coated zeolite crystal films as surface-enhanced Raman scattering
      substrates.
AB  - Silver-coated zeolite A and zeolite NaX crystal films prepared by vacuum
      deposition were investigated as surface-enhanced Raman scattering (SERS)
      substrates. The substrates were active for the enhancement of Raman scattering
      from uranyl ions. A detection limit of 10(-5) M for uranyl was obtained using
      silver-coated zeolite A films. One advantage of these zeolite-based substrates is
      that the negatively charged microporous framework provides the selectivity for
      adsorption based on static electric charges. The SERS effects of positively
      charged uranyl ions and neutrally charged benzoic acid were compared. For the
      zeolite A substrate, there was a 100-times-greater sensitivity.

PMID- 14727717
TI  - Novel method for preparing controllable and stable silver particle films for
      surface-enhanced Raman scattering spectroscopy.
AB  - A new surface-enhanced Raman scattering (SERS) active substrate has been
      developed based on our previous study. Small silver nanoparticles on a quartz
      slide can be enlarged by using a mixture of commercially available reagents
      called Silver Enhancer and Initiator. The optical properties and characteristics
      of the new substrate have been investigated by ultraviolet-visible (UV-Vis)
      spectroscopy and atomic force microscopy (AFM). The results indicate that the
      small silver nanoparticles grow and some silver aggregates emerge on the quartz
      slide after the slide is immersed into the Silver Enhancer and Initiator Mixture
      (SEIM). The average diameter of the silver nanoparticles on the substrate becomes
      approximately double after the immersion into SEIM for 20 s. 1,4-bis[2-(4
      pyridyl)ethenyl]-benzene (BPENB) was used as a Raman probe to evaluate the
      enhancement ability of the new silver substrate. It has been found that the SERS
      intensity can be increased about 10 times by using the substrate treated by SEIM
      compared with that without being treated by SEIM. Interestingly enough, the SERS
      enhancement increases with time. This may be due to the reorganization of silver
      nanoparticles on the quartz surface. The new substrate can remain active for more
      than 90 days. The adsorption mode of BPENB on the new substrate and the
      dependence of the BPENB configurations on the concentration of BPENB in methanol
      solution have also been investigated by SERS or UV-Vis spectroscopy. The SERS
      spectra of a self-assembled monolayer (SAM) BPENB film adsorbed on a silver
      substrate treated by SEIM show that BPENB molecules are chemically absorbed
      through the Ag-N bond. Consequently, a nearly perpendicular orientation of BPENB
      on the silver surface is proposed. The SERS spectra of BPENB SAMs on the new
      substrates fabricated from methanol solutions with different concentrations are
      compared. The concentration dependence of the SERS spectra reveals that the BPENB
      molecules are adsorbed on the silver film as monomers when the film is prepared
      from the solution with a lower concentration (<4 x 10(-6) M) and as aggregates
      when it is prepared from the solution with a higher concentration (>1 x 10(-5)
      M).

PMID- 14727718
TI  - Surface-enhanced Raman spectroscopy as a tool for probing specific biochemical
      components in bacteria.
AB  - Treatment of bacteria with silver yields intense and highly specific surface
      enhanced Raman spectroscopy (SERS) spectra from various cellular chemical
      components located in the vicinity of the silver colloids. In particular, we
      demonstrate an extreme sensitivity to flavin components associated with the cell
      envelope and to their state of oxidation. Different spectra, possibly associated
      with DNA, carboxylates, and perhaps phosphates, are obtained from the soluble
      interior fraction of the cell.

PMID- 14727719
TI  - Real-time in situ Raman analysis of microwave-assisted organic reactions.
AB  - Integration of a Raman probe into a commercially available microwave synthesizer
      has demonstrated unprecedented utility in understanding chemical processes within
      the rapidly emerging field of microwave-assisted organic synthesis. The real-time
      spectral feedback afforded by this system has facilitated analysis of reaction
      mechanisms, reactive intermediates, and reaction kinetics via optical sampling
      through the sidewall of the sealed reaction vial within the microwave chamber.
      The feasibility, attributes, and limitations of the system are illustrated using
      amine coupling and Knoevenagel coupling example reactions. In addition to the
      reported analyses, this system provided the safety of remote sensing, adequate
      sensitivity, ease of alignment, and optimized "depth of field" for analysis of
      solutions with solids content.

PMID- 14727720
TI  - Spectra and concentration profiles throughout the reaction of curing epoxy resins
      from near-infrared spectroscopy and multivariate curve resolution methods.
AB  - When applied to near-infrared (NIR) data, multivariate curve resolution methods,
      in particular alternating least squares (ALS), make it possible to calculate the
      concentration profiles and the spectra of all species involved in the reaction of
      curing epoxy resins. In this paper, the model reaction between phenyl glicidyl
      ether and aniline (2:1) was studied at 95 degrees C. A NIR spectrum was recorded
      every five minutes throughout the eight-hour reaction process. The data display
      rank deficiency. This problem was overcome by supplying additional information to
      the system in the form of known spectra of some reactants. The recovered spectra
      and concentration profiles satisfactorily reproduced the experimental data. In
      this way, 99.99% of the variance associated with the experimental matrix was
      reproduced. A value of 0.87% was obtained for lack of fit while the similarity
      coefficient r between the spectra recovered and the spectra corresponding to the
      three pure species involved in the reaction were PGE (r = 0.994), aniline (r =
      0.994), and tertiary amine (r = 0.999). The maximum and minimum limits associated
      with the ALS solutions were calculated, which made it possible to limit to a
      considerable extent the ambiguity that is characteristic of these curve
      resolution methods.

PMID- 14727721
TI  - Multiway calibration for creatinine determination in human serum using the Jaffe
      reaction.
AB  - Second-order calibration and multivariate spectroscopic-kinetic measurements in
      the visible region are proposed to improve the Jaffe method for creatinine assay.
      Analyses performed on synthetic mixtures containing bilirubin, glucose, and
      albumin confirm that second-order calibration is useful for creatinine
      determination in human serum. Quantitative determinations of creatinine with the
      parallel factor analysis (PARAFAC) and direct trilinear decomposition (TLD)
      methods were compared. It is shown that both methods can be used for creatinine
      determination in human serum, with an SEP (standard error of prediction) of 2.22
      and coefficient of variability of 6.14% for PARAFAC, and an SEP of 2.38 and
      coefficient of variability of 6.57% for TLD [corrected].

PMID- 14727722
TI  - Effects of CaCl2 and MgCl2 on Fourier transform infrared spectra of lung cancer
      cells.
AB  - The cations Ca2+ and Mg2+ are two important factors in the growth and maintenance
      of living cells. The addition of Ca2+ to living cells can cause a change in the
      three-dimensional (3D) structure of calcium binding proteins. Therefore, we
      decided to study whether the addition of CaCl2 and MgCl2 to three in vitro
      growing lung cancer cell lines could cause changes that could be measured by
      Fourier Transform Infrared Spectroscopy. The addition of CaCl2 or MgCl2 to lung
      cancer cells caused an increase in absorbance of the trough at 1410 cm(-1). This
      translated into an inversion of the 1410/1395 cm(-1) ratio following the addition
      of CaCl2 or MgCl2 for all three lung cancer cell lines. Also, the amide I peak
      shifted from around 1631 cm(-1) to lower wavenumbers when CaCl2 or MgCl2 was
      added to cancer cells. Furthermore, the addition of these two substances caused a
      shift of the peak between 3290 and 3395 cm(-1). Finally, while the addition of
      CaCl2 to lung cancer cells was associated with an increased cell death, this was
      not the case following the addition of MgCl2. This would confirm that the changes
      seen in the spectra of all three cell lines are due to metabolic and ionic shifts
      rather than cell death.

PMID- 14727723
TI  - Analysis of 1H/2H exchange kinetics using model infrared spectra.
AB  - This paper investigates the different approaches that best retrieve band shape
      parameters and kinetic time constants from series of protein Fourier transform
      infrared (FT-IR) spectra recorded in the course of 1H/2H exchange. In this first
      approach, synthetic spectra were used. It is shown that 1H/2H exchange kinetic
      measurements can help resolve spectral features otherwise hidden because of the
      overlap of various spectral contributions. We evaluated the efficiency of Fourier
      self-deconvolution, synchronous/asynchronous correlation, difference
      spectroscopy, principal component analysis, inverse Laplace transform, and
      determination of the underlying spectra by global analysis assuming first-order
      kinetics with either known or unknown time constants. It is demonstrated that
      some strategies allow the extraction of both the time dependence and the spectral
      shape of the underlying contributions.

PMID- 14727724
TI  - Two multivariate strategies applied to three-way kinetic spectrophotometric data
      for the determination of mixtures of the pesticides carbaryl and chlorpyrifos.
AB  - Two pesticides, carbaryl and chlorpyrifos, have been simultaneously determined
      using second-order kinetic spectrophotometric measurements upon alkaline
      oxidative degradation. In spite of the complexity of the system and of the
      serious spectral overlap among the reagents and products, calibration and
      prediction is possible thanks to the power of second-order multivariate
      techniques. Strategies such as parallel factor analysis (PARAFAC) and
      multivariate curve resolution coupled to alternating least-squares (MCR-ALS) have
      been employed, which adequately exploit the second-order advantage. They allow
      for a correct determination of the analytes both in synthetic binary samples and
      in a commercial formulation, in this latter case even in the presence of
      unmodeled interferents. Multi-way partial least-squares (n-PLS) produced good
      results only on synthetic binary mixtures but could not be applied to a
      commercial sample because it contained an uncalibrated component.

PMID- 14727726
TI  - Broadband light profile microscopy: a rapid and direct method for thin film depth
      imaging.
AB  - Light profile microscopy (LPM) is a recently developed technique of optical
      inspection that is used to record micrometer scale images of thin film cross
      sections on a direct basis. This technique uses a novel right-angle imaging
      geometry that shows outstanding contrast for subtle interface structures and
      morphologies that are invisible to conventional methods of inspection. When laser
      sources are used for sample illumination, image contrast is provided by
      luminescence and elastic and/or inelastic scatter. When a white-light excitation
      source is used for LPM, primary contrast is obtained from elastic scatter, while
      secondary contrast results from refraction, secondary transmission, and secondary
      reflection from material phases. We term this mode of inspection broadband light
      profile microscopy (BB-LPM). It is implemented with a compact, easily aligned
      apparatus and minimal sample preparation, and it shows outstanding interface
      contrast similar to laser LPM. In this work we demonstrate BB-LPM as a method for
      direct imaging of the layers structures of a variety of thin film samples of
      industrial and manufacturing interest.

PMID- 14727725
TI  - Utilizing three-dimensional fluorescence's red-shift cascade effect to monitor
      mycobacterium PRY-1 degradation of aged petroleum.
AB  - Samples of Mycobacterium PRY-1 inoculated motor oil are subjected to three
      dimensional fluorescence spectroscopy to document the shifting of
      excitation/emission maxima as the solutions undergo serial dilutions. Effects
      such as self-quenching of individual polycyclic aromatic hydrocarbons (PAHs) and
      energy transfer between PAHs combine to produce large red-shifts in the resulting
      fluorescence emission spectra. This process is repeated over a series of weeks
      and is compared to preceding spectra to gauge the microbial degradation of the
      petroleum. Results show a two-fold, or 75%, PAH contaminant degradation by
      Mycobacterium PRY-1 over a 140-day growth period.

PMID- 14727728
TI  - Continuous monitoring of alkali metals in gas flows using direct-current plasma
      excited atomic spectroscopy.
AB  - A measuring instrument employing direct current (dc) plasma excited atomic line
      spectroscopy was developed for continuous measurement of alkali in combustion
      flue gases. Alkali compounds are dissociated by mixing sampled flue gas with a
      nitrogen plasma jet generated with a non-transferred dc plasma torch. The
      instrument can be used in two operating modes. The molar fraction is determined
      either by measuring the transmittance of the gas jet or by monitoring the
      emission. A tungsten halogen lamp and scanning monochromator are used for the
      measurement of the optical signals. Measurement of sodium and potassium has been
      demonstrated. The detection limits of the instrument are 50-70 ppb in the
      absorption mode. The detection limits are 2-3 ppb at 0.1 MPa pressure and 0.1-0.2
      ppb at 1.0 MPa in the emission mode. The instrument is designed to withstand
      corrosive, particle laden, and pressurized flue gases at temperatures up to 1373
      K.

PMID- 14727727
TI  - Determination of phosphorous and sulfur in environmental samples by
      electrothermal vaporization inductively coupled plasma atomic emission
      spectrometry.
AB  - From the viewpoint of selective introduction of the analyte from its solvent and
      matrices, electrothermal vaporization (ETV) is useful for the sample introduction
      into the inductively coupled plasma (ICP). By using a tungsten boat furnace (TBF)
      vaporizer system, the loss of analyte phosphorus, which normally occurs during
      the drying and ashing stages, is suppressed. The phosphate ion is reacted with
      the tungsten supplied from the surface of the TBF to form stable tungsten
      phosphate species. Regarding the determination of sulfur, additional chemical
      modifiers such as copper(II), lead(II), etc., are necessary to retain the analyte
      on the TBF. The furnace-fusion (FF) method or wet-digestion technique on the TBF
      is applied to unify the chemical forms of the analytes. Various oxidative and
      reductive inorganic compounds as well as organic compounds of phosphorus and
      sulfur show the same sensitivities after the FF digestion with hydrogen peroxide.
      The detection limits are 1.5 ng and 0.12 ng for phosphorous and sulfur,
      respectively. The repeatabilities in terms of the relative standard deviations of
      10 replicate measurements of phosphorus and sulfur are 4.2% and 2.0%,
      respectively. Finally, the established method is applied to the determination of
      several environmental waters.

PMID- 14727729
TI  - Influence of the laser pulse duration on spectrochemical analysis of solids by
      laser-induced plasma spectroscopy.
AB  - Quantitative analysis of aluminum and copper alloys by means of laser-induced
      plasma spectroscopy (LIPS) has been investigated for three representative laser
      pulse durations (80 fs, 2 ps, and 270 ps). The experiments were carried out in
      air at atmospheric pressure with a constant energy density of 20 J/cm2. Because
      the decay rate of the spectral emission depends on the laser pulse duration, the
      optimum detection requires an optimization of the temporal gating acquisition
      parameters. LIPS calibration (sensitivity and nonlinearity) and the limit of
      detection (LOD) are discussed in detail. While the LOD of minor elements embedded
      in alloy samples obtained by sub-picosecond or sub-nanosecond laser pulses are
      both time and element dependent, provided an appropriate temporal window is
      chosen, the optimum LODs (several parts per million (ppm)) prove to be
      independent of the laser pulse duration. Finally, it is found that for elements
      such as those detected here, gated LIPS spectra using picosecond or sub
      picosecond laser pulses provide much better LOD values than non-gated spectra.

PMID- 14727730
TI  - Integrated gas analyzer for complete monitoring of turbine engine test cells.
AB  - Fourier transform infrared (FT-IR) spectroscopy is proving to be reliable and
      economical for the quantification of many gas-phase species during testing and
      development of gas turbine engines in ground-based facilities such as sea-level
      test cells and altitude test cells. FT-IR measurement applications include engine
      generated exhaust gases, facility air provided as input to engines, and ambient
      air in and around test cells. Potentially, the traditionally used assembly of
      many gas-specific single gas analyzers will be eliminated. However, the quest for
      a single instrument capable of complete gas-phase monitoring at turbine engine
      test cells has previously suffered since the FT-IR method cannot measure infrared
      inactive oxygen molecules, a key operational gas to both air-breathing propulsion
      systems and test cell personnel. To further the quest, the FT-IR sensor used for
      the measurements presented in this article was modified by integration of a
      miniature, solid-state electrochemical oxygen sensor. Embedded in the FT-IR unit
      at a location near the long-effective-optical-path-length gas sampling cell, the
      amperometric oxygen sensor provides simultaneous, complementary information to
      the wealth of spectroscopic data provided by the FT-IR method.

PMID- 14727731
TI  - Reference sample method reduces the error caused by variable cryosection
      thickness in Fourier transform infrared imaging.
AB  - Fourier transform infrared imaging (FT-IRI) is a novel technique for
      characterization of the biochemical composition of biological tissues, e.g.,
      articular cartilage. The use of cryosections is preferred in FT-IRI.
      Unfortunately, significant variation in section thickness often impairs the
      suitability of cryosections for quantitative FT-IRI analysis. The present study
      introduces an inexpensive reference sample method for quantitative analysis. In
      this technique, specimen absorption is normalized with that of nitrocellulose
      membrane embedded and cryosectioned with the sample. Mean variation of the
      infrared absorption in cartilage specimens was 11.5%, 12.1%, and 20.6% for 5
      microm, 10 microm, and 14 microm thick sections, respectively, without
      normalization. Normalization reduced the variation to 5.2%, 4.0%, and 4.6% for
      the same sections, respectively. The normalization method enables usage of
      cryosections for quantitative work and significantly reduces the cost and time
      needed for FT-IRI analysis.

PMID- 14727732
TI  - The human relevance of information on carcinogenic modes of action: overview.
AB  - Risk assessment policies and practice place increasing reliance on mode of action
      (MOA) data to inform conclusions about the human relevance of animal tumors. In
      June 2001, the Risk Science Institute of the International Life Sciences
      Institute formed a workgroup to study this issue. The workgroup divided into two
      subgroups, one developing and testing a "framework" for MOA relevance analysis
      and the other conducting an in-depth analysis of peroxisome proliferation
      activated receptor (PPAR)alpha activation as the MOA for some animal carcinogens.
      This special issue of Critical Reviews in Toxicology presents the scientific
      reports emerging from this activity. These reports serve several purposes. For
      risk assessors in and out of government, they offer a new human relevance
      framework (HRF) that complements and extends existing guidance from other
      organizations. Regarding the specific MOA for peroxisome proliferating chemicals,
      these reports offer a state-of-the-science review of this important MOA and its
      role in tumorigenesis in three different tissues (liver, testis, and pancreas).
      The case studies in these reports present models for using MOA information to
      evaluate the hazard potential for humans. The cases also illustrate the
      substantial impact of a complete human relevance analysis, as distinct from an
      animal MOA analysis alone, on the nature and scope of risk assessment.

PMID- 14727733
TI  - A framework for human relevance analysis of information on carcinogenic modes of
      action.
AB  - The human relevance framework (HRF) outlines a four-part process, beginning with
      data on the mode of action (MOA) in laboratory animals, for evaluating the human
      relevance of animal tumors. Drawing on U.S. EPA and IPCS proposals for animal MOA
      analysis, the HRF expands those analyses to include a systematic evaluation of
      comparability, or lack of comparability, between the postulated animal MOA and
      related information from human data sources. The HRF evolved through a series of
      case studies representing several different MOAs. HRF analyses produced divergent
      outcomes, some leading to complete risk assessment and others discontinuing the
      process, according to the data available from animal and human sources. Two case
      examples call for complete risk assessments. One is the default: When data are
      insufficient to confidently postulate a MOA for test animals, the animal tumor
      data are presumed to be relevant for risk assessment and a complete risk
      assessment is necessary. The other is the product of a data-based finding that
      the animal MOA is relevant to humans. For the specific MOA and endpoint
      combinations studied for this article, full risk assessments are necessary for
      potentially relevant MOAs involving cytotoxicity and cell proliferation in
      animals and humans (Case Study 6, chloroform) and formation of urinary-tract
      calculi (Case Study 7, melamine). In other circumstances, when data-based
      findings for the chemical and endpoint combination studied indicate that the
      tumor-related animal MOA is unlikely to have a human counterpart, there is little
      reason to continue the risk assessment for that combination. Similarly, when
      qualitative considerations identify MOAs specific to the test species or
      quantitative considerations indicate that the animal MOA is unlikely to occur in
      humans, such hazard findings are generally conclusive and further risk assessment
      is not necessary for the endpoint-MOA combination under study. Case examples
      include a tumor-related protein specific to test animals (Case Study 3, d
      limonene), the tumor consequences of hormone suppression typical of laboratory
      animals but not humans (Case Study 4, atrazine), and chemical-related enhanced
      hormone clearance rates in animals relative to humans (Case Study 5,
      phenobarbital). The human relevance analysis is highly specific for the chemical
      MOA-tissue-endpoint combination under analysis in any particular case: different
      tissues, different endpoints, or alternative MOAs for a given chemical may result
      in different human relevance findings. By providing a systematic approach to
      using MOA data, the HRF offers a new tool for the scientific community's overall
      effort to enhance the predictive power, reliability and transparency of cancer
      risk assessment.

PMID- 14727734
TI  - PPARalpha agonist-induced rodent tumors: modes of action and human relevance.
AB  - Widely varied chemicals--including certain herbicides, plasticizers, drugs, and
      natural products--induce peroxisome proliferation in rodent liver and other
      tissues. This phenomenon is characterized by increases in the volume density and
      fatty acid oxidation of these organelles, which contain hydrogen peroxide and
      fatty acid oxidation systems important in lipid metabolism. Research showing that
      some peroxisome proliferating chemicals are nongenotoxic animal carcinogens
      stimulated interest in developing mode of action (MOA) information to understand
      and explain the human relevance of animal tumors associated with these chemicals.
      Studies have demonstrated that a nuclear hormone receptor implicated in energy
      homeostasis, designated peroxisome proliferator-activated receptor alpha
      (PPARalpha), is an obligatory factor in peroxisome proliferation in rodent
      hepatocytes. This report provides an in-depth analysis of the state of the
      science on several topics critical to evaluating the relationship between the MOA
      for PPARalpha agonists and the human relevance of related animal tumors. Topics
      include a review of existing tumor bioassay data, data from animal and human
      sources relating to the MOA for PPARalpha agonists in several different tissues,
      and case studies on the potential human relevance of the animal MOA data. The
      summary of existing bioassay data discloses substantial species differences in
      response to peroxisome proliferators in vivo, with rodents more responsive than
      primates. Among the rat and mouse strains tested, both males and females develop
      tumors in response to exposure to a wide range of chemicals including DEHP and
      other phthalates, chlorinated paraffins, chlorinated solvents such as
      trichloroethylene and perchloroethylene, and certain pesticides and hypolipidemic
      pharmaceuticals. MOA data from three different rodent tissues--rat and mouse
      liver, rat pancreas, and rat testis--lead to several different postulated MOAs,
      some beginning with PPARalpha activation as a causal first step. For example,
      studies in rodent liver identified seven "key events," including three "causal
      events"--activation of PPARalpha, perturbation of cell proliferation and
      apoptosis, and selective clonal expansion--and a series of associative events
      involving peroxisome proliferation, hepatocyte oxidative stress, and Kupffer-cell
      mediated events. Similar in-depth analysis for rat Leydig-cell tumors (LCTs)
      posits one MOA that begins with PPARalpha activation in the liver, but two
      possible pathways, one secondary to liver induction and the other direct
      inhibition of testicular testosterone biosynthesis. For this tumor, both proposed
      pathways involve changes in the metabolism and quantity of related hormones and
      hormone precursors. Key events in the postulated MOA for the third tumor type,
      pancreatic acinar-cell tumors (PACTs) in rats, also begin with PPARalpha
      activation in the liver, followed by changes in bile synthesis and composition.
      Using the new human relevance framework (HRF) (see companion article), case
      studies involving PPARalpha-related tumors in each of these three tissues
      produced a range of outcomes, depending partly on the quality and quantity of MOA
      data available from laboratory animals and related information from human data
      sources.

PMID- 14727735
TI  - Alternative oxidase reduces the sensitivity of Mycosphaerella graminicola to QOI
      fungicides.
AB  - Forty-six (1.5%) of nearly 3000 isolates of Mycosphaerella graminicola assayed in
      vitro were resistant to the QOI fungicide azoxystrobin, but on sub-culturing only
      ten remained resistant. Cross-resistance extended to other QOIs, but varied
      between different isolates. In planta the resistant isolates were not well
      controlled, especially at lower azoxystrobin dose rates. Propyl gallate, an
      inhibitor of alternative oxidase, potentiated the activity of azoxystrobin in
      vitro so that resistance was no longer observed. The growth of resistant strains
      in the presence of azoxystrobin led to alternative oxidase activation. This
      increased flexibility in respiration allows resistant strains to survive in the
      presence of a QOI fungicide. Under these conditions, selection for target-site
      mutations can occur. Using QOIs preventatively reduces the risk of resistance
      since the alternative oxidase cannot by itself generate all the energy needed for
      germination and early infection.

PMID- 14727736
TI  - Use of PRZM-3 to validate a laboratory to field degradation conceptual model.
AB  - The test substance, boscalid, was applied at two field sites, but, depending on
      how kinetic calculations were performed, the time required for 50% of the initial
      compound concentration to dissipate (half-life) ranged from 27 to 200 days.
      Laboratory aerobic soil studies indicated that the DT50 for the compound was
      about 108 days, and since compound dissipation rates are typically shorter in the
      field than those observed in the laboratory, confidence in the field half-life
      calculations was questioned. Researchers have asked whether exposure models might
      be useful for relating laboratory to field behavior, especially when results are
      difficult to reconcile between the two systems. In order to determine how
      realistic field dissipation-time kinetic calculations were, a 60-day DT50 (some
      masked data), 150-day DT50 and a 196-day rate constant (t1/2) kinetic result were
      entered into the Pesticide Root Zone Model (PRZM-3) for a California site. A 27
      day DT50, and a 200 day t1/2 kinetic result were also entered into the model for
      a Florida site. Results indicate that using the shortest DT50 solution in PRZM-3
      provided the best fit to actual field data. Results from this study suggest that
      PRZM-3 can be used successfully to address uncertainty between a laboratory
      conceptual understanding of a compound's behavior and the actual behavior
      observed in the field.

PMID- 14727737
TI  - Herbicide safety relative to common targets in plants and mammals.
AB  - Most modern herbicides have low mammalian toxicity. One of the reasons for this
      safety is that the target site for the herbicides is not often present in
      mammals. There are approximately 20 mechanisms of action that have been
      elucidated for herbicides. Of these, some do share common target sites with
      mammals. The mechanisms include formation of free radicals, protoporphyrinogen
      oxidase (PROTOX), glutamine synthetase (GS) and 4-hydroxyphenylpyruvate
      dioxygenase (HPPD). PROTOX, HPPD and GS inhibitors have been shown to inhibit
      these enzymes in both plants and mammals and there are measurable effects in
      mammalian systems. However, the consequences of inhibiting a common target site
      in plants can be quite different than in animals. What may be a lethal event in
      plants, eg inhibition of HPPD, can have a beneficial effect in mammals, eg
      treatment for tyrosinemia type I. These chemicals also have low mammalian
      toxicity due to rapid metabolism and/or excretion of the herbicide from mammalian
      systems.

PMID- 14727738
TI  - The discovery of pyridalyl: a novel insecticidal agent for controlling
      lepidopterous pests.
AB  - Synthesis of analogues of two compounds with known insecticidal activity, both of
      which contain a 3,3-dichloro-2-propenyloxy group, produced 2-(trifluoromethyl)-4
      phenoxyphenyl 3,3-dichloro-2-propenyl ether, which had weak activity against
      lepidopterous larvae. Structural modifications around this lead compound led to
      the development of pyridalyl [Pleo, S-1812; 2,6-dichloro-4-(3,3
      dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether], which
      belongs to a new class of insecticides. Pyridalyl gives very good control of
      various lepidopterous and thysanopterous pests on cotton and vegetables, without
      phytotoxicity. It controls populations of Heliothis virescens F and Plutella
      xylostella (L) which are resistant to various currently used insecticides. It
      also produces unique insecticidal symptoms, so it may have a different mode of
      action from other existing insecticides. Pyridalyl is also less harmful than
      existing insecticides to various beneficial arthropods, so it should provide an
      important tool in IPM and insecticidal management programmes for the control of
      lepidopterous and thysanopterous pests. The first market introduction is expected
      in Japan and some Asian countries in the years between 2004 and 2005.

PMID- 14727739
TI  - Multiple origins for black-grass (Alopecurus myosuroides Huds) target-site-based
      resistance to herbicides inhibiting acetyl-CoA carboxylase.
AB  - We have investigated the process of evolution of target-site-based resistance to
      herbicides inhibiting acetyl-CoA carboxylase (ACCase) in nine French populations
      of black-grass (Alopecurus myosuroides Huds). To date, two different ACCase
      resistant alleles are known. One contains an isoleucine-to-leucine substitution
      at position 1781, the second contains an isoleucine-to-asparagine substitution at
      position 2041. Using phylogenetic analysis of ACCase sequences, we showed that
      1781Leu ACCase alleles evolved from four independent origins in the nine black
      grass populations studied, while 2041Asn ACCase alleles evolved from six
      independent origins. No geographical structure of black-grass populations was
      revealed. This implies that these populations, although geographically distant,
      are, or have until recently been, connected by gene flows. Comparison of
      biological data obtained from herbicide sensitivity bioassay and molecular data
      showed that distinct resistance mechanisms often exist in a single black-grass
      population. Accumulation of different resistance mechanisms in a single plant was
      also demonstrated. We conclude that large-scale evolution of resistance to
      herbicides in black-grass is a complex phenomenon, resulting from the independent
      selection of various resistance mechanisms in local black-grass populations
      undergoing contrasted herbicide and agronomical selection pressures, and
      connected by gene flows whose parameters remain to be determined.

PMID- 14727740
TI  - Distribution and persistence of emamectin benzoate at efficacious concentrations
      in pine tissues after injection of a liquid formulation.
AB  - In an earlier paper the authors reported the creation of a novel emamectin
      benzoate 40 g litre(-1) liquid formulation (Shot Wan Liquid Formulation). The
      injection of this formulation exerted a preventative effect against the pine wilt
      disease caused by the pine wood nematode, Bursaphelenchus xylophilus (Steiner &
      Buhrer) Nickle, and this effect lasted for at least 3 years. The present study
      was carried out to show experimentally that the marked effect of this formulation
      was due to the presence and persistence in pine tissues of sufficient amounts of
      emamectin benzoate to inhibit nematode propagation. A cleanup procedure prior to
      quantitative analysis of emamectin benzoate by fluorescence HPLC was devised. The
      presence of the compound in concentrations sufficient to inhibit nematode
      propagation in the shoots of current growth and its persistence for 3 years
      explained the marked preventative effect. Non-distribution of emamectin benzoate
      in some parts of the lower trunk suggested that the formulation should be
      injected at several points for large trees in order to distribute the compound
      uniformly to lower branches.

PMID- 14727741
TI  - Biotransformation of atrazine in transgenic tobacco cell culture expressing human
      P450.
AB  - Plant cell cultures in which the appropriate P450 cDNA is introduced are expected
      to metabolise certain pesticides in large quantities. Two species of human P450
      (CYP1A1 and CYP1A2) were introduced into tobacco cells (Nicotiana tabacum L) by
      Agrobacterium-mediated transformation. The transgenic plant cell cultures were
      selected by combination of kanamycin-resistance, 7-ethoxycoumarin O-de-ethylase
      activity, PCR and Western blot analysis. For metabolism studies, 14C-labelled
      atrazine was used as a model substance. The metabolites de-ethylatrazine and de
      isopropylatrazine were found in the control culture as well as in the transgenic
      culture, whereas the non-phytotoxic metabolite de-ethyl-de-isopropylatrazine was
      found only in the transgenic cell cultures. The results showed that both foreign
      enzymes CYP1A1 and CYP1A2 catalyse N-dealkylation of atrazine. However, CYP1A2
      exhibited a higher conversion rate than CYP1A1. In a time-course study the enzyme
      CYP1A2 catalysed predominantly N-de-ethylation followed by de-isopropylation. The
      extent of metabolism was considerably higher than in non-transformed cell
      cultures. The transgenic cell cultures can therefore be suitable tools for the
      production of large quantities of primary oxidised pesticide metabolites.

PMID- 14727742
TI  - Chiral response of Oryzeae and Paniceae plants in alpha-methylbenzyl-3-p-tolyl
      urea agar medium.
AB  - The results presented here support the hypothesis that plants of the tribe
      Oryzeae respond enantioselectively and homogeneously to optically active 1-alpha
      methylbenzyl-3-p-tolylurea (MBTU) in root growth inhibition, in contrast to
      Echinochloa species. The Oryzeae plants tested in this study belong to different
      genera (Oryza, Leersia, Chikusichloa and Zizania), to different species (O
      sativa, O glaberrima, O alta, O coarctata, O latifolia, O minuta, O rufipogon),
      to various ecospecies of Oryza (japonica, indica, japonica x indica, javanica)
      and to different levels of evolution [cultivated rice (O sativa and O glaberrima)
      and ancestral wild rice species]. In spite of their different phylogenic status
      and diverse sensitivity, the root growth of all members of the genus Oryza was
      inhibited more by R-MBTU than by S-MBTU. Zizania palustris, Z latifolia, Leersia
      oryzoides and Chikusichloa aquatica belonging to the tribe Oryzeae exhibited
      similar chiral recognition to the Oryza plants, suggesting that Oryzeae have a
      common chiral recognition mechanism in their response to optically active MBTUs.
      In contrast, Echinochloa plants (E crus-galli (L) Beauv var crus-galli and E
      colonum (L) Link), belonging into subfamily Panicoideae tribe Paniceae, responded
      in a different way, where their root growth was more sensitive to S-MBTU than to
      the antipodal R-MBTU. A reverse chiral response between the tribe Oryzeae and the
      genus Echinochloa was clearly indicated in this study. This diverse response may
      be relevant to Gramineae classification.

PMID- 14727743
TI  - Characterization of the bound residues of the fungicide cyprodinil formed in
      plant cell suspension cultures of wheat.
AB  - The non-extractable residues of the fungicide cyprodinil formed in heterotrophic
      cell suspension cultures of wheat were studied by application of [2-pyrimidyl
      14C] or [2-pyrimidyl-13C]cyprodinil. The main objective was to examine whether
      solid-state and liquid 13C NMR spectroscopy can be used to examine plant bound
      residues of pesticides. For 14C experiments, wheat suspensions grown on glucose
      as carbon source were treated with 10 mg litre(-1) of 14C-cyprodinil. After
      incubation for 12 days, 20% of applied 14C was detected as non-extractable
      residues. The cell debris were treated with 0.1 M HCl (reflux), 1.0 M HCl
      (reflux), buffer, or 2 M NaOH (50 degrees C); Bjorkman lignin and acidolysis
      lignin fractions were also prepared from the debris. Radioactivity liberated and
      solubilized by these procedures was examined by thin-layer chromatography and
      high-performance liquid chromatography. The results showed that cyprodinil and
      primary metabolites contributed to the fungicide's bound residues. Most of the
      residues (12% of applied 14C) remained associated with polar or
      polymeric/oligomeric endogenous cell materials in a stable manner. For the study
      with 13C-cyprodinil, wheat suspensions were cultivated on 13C-depleted glucose
      for four growth cycles, resulting in maximum 13C depletion of the natural cell
      components to about 0.10%. During the fourth cycle, 13C-labelled cyprodinil was
      applied, and cells were incubated (12 days). Cell debris was prepared and
      examined by solid-state 13C NMR spectroscopy. Debris was then treated as
      described above in the 14C experiment. Solubilized fractions were analyzed by
      liquid 13C NMR spectroscopy. However, none of the 13C NMR spectra recorded gave
      utilizable or unambiguous results, and all exhibited large inconsistencies,
      especially concerning the data from the conventional 14C experiment.

PMID- 14727744
TI  - Fate of the insecticide lambda-cyhalothrin in ditch enclosures differing in
      vegetation density.
AB  - Use of the insecticide lambda-cyhalothrin in agriculture may result in the
      contamination of water bodies, for example by spray drift. Therefore, the
      possible exposure of aquatic organisms to this insecticide needs to be evaluated.
      The exposure of the organisms may be reduced by the strong sorption of the
      insecticide to organic materials and its susceptibility to hydrolysis at the high
      pH values in the natural range. In experiments done in May and August, formulated
      lambda-cyhalothrin was mixed with the water body of enclosures in experimental
      ditches containing a bottom layer and macrophytes (at different densities) or
      phytoplankton. Concentrations of lambda-cyhalothrin in the water body and in the
      sediment layer, and contents in the plant compartment, were measured by gas
      liquid chromatography at various times up to 1 week after application. Various
      water quality parameters were also measured. Concentrations of lambda-cyhalothrin
      decreased rapidly in the water column: 1 day after application, 24-40% of the
      dose remained in the water, and by 3 days it had declined to 1.8-6.5%. At the
      highest plant density, lambda-cyhalothrin residue in the plant compartment
      reached a maximum of 50% of the dose after 1 day; at intermediate and low plant
      densities, this maximum was only 3-11% of the dose (after 1-2 days). The
      percentage of the insecticide in the ditch sediment was 12% or less of the dose
      and tended to be lower at higher plant densities. Alkaline hydrolysis in the
      water near the surface of macrophytes and phytoplankton is considered to be the
      main dissipation process for lambda-cyhalothrin.

PMID- 14727745
TI  - Cross-resistance pattern and alternative herbicides for Cyperus difformis
      resistant to sulfonylurea herbicides in Korea.
AB  - A Cyperus difformis L accession from Chonnam province, Korea was tested for
      resistance to the sulfonylurea herbicide, imazosulfuron. The accession was
      confirmed to be resistant (R) and was cross-resistant to other sulfonylurea
      herbicides, bensulfuron-methyl, cyclosulfamuron and pyrazosulfuron-ethyl, the
      pyrimidinyl thiobenzoate herbicide, bispyribac-sodium, and the imidazolinone
      herbicide imazapyr, but not to imazaquin. Multiple resistance was tested using
      twelve herbicides with target sites other than acetolactate synthase (ALS). The R
      biotype could be controlled by other herbicides with different modes of action
      such as butachlor, carfentrazone-ethyl, clomeprop, dithiopyr, esprocarb,
      mefenacet, oxadiazon, pretilachlor, pyrazolate and thiobencarb, applied to soil
      at recommended rates. Several sulfonylurea herbicide-based mixtures can control
      both the R and S biotypes of C difformis, except sulfonylurea plus dimepiperate,
      molinate or pyriftalid, and pyrazolate plus butachlor. Although mixtures of
      sulfonylurea herbicides might be more effective, they should be avoided and used
      only in special cases. In terms of in vitro ALS activity, the R biotype was 1139
      , 3583-, 1482-, 416-, 5- and 9-fold more resistant to bensulfuron-methyl,
      cyclosulfamuron, imazosulfuron, pyrazosulfuron-ethyl, bispyribac-sodium and
      imazapyr, respectively, than the S biotype. The in vivo ALS activity of the R
      biotype was also less affected by the sulfonylurea herbicides, imazosulfuron and
      pyrazosulfuron-ethyl, than the S biotype. Results of in vitro and in vivo ALS
      assays indicated that the resistance mechanism of C difformis to ALS inhibitor
      herbicides was primarily due to an alteration in the target enzyme, ALS.
      Greenhouse experiments showed delayed flowering and reduced seed production of
      the R biotype, which could possibly result in reduced fitness. This unusual
      observation needs to be confirmed in field situations.

PMID- 14727746
TI  - Persistence and residual activity of an organophosphate, pirimiphos-methyl, and
      three IGRs, hexaflumuron, teflubenzuron and pyriproxyfen, against the cowpea
      weevil, Callosobruchus maculatus (Coleoptera: Bruchidae).
AB  - Three insect growth regulators (IGR), the chitin synthesis inhibitors (CSI)
      teflubenzuron and hexaflumuron and the juvenile hormone mimic (JHM) pyriproxyfen,
      as well as the organophosphate (OP) pirimiphos-methyl, were evaluated for their
      activity against the cowpea weevil, Callosobruchus maculatus (F), in cowpea seeds
      stored for up to 8 months post-treatment. The initial activity data showed that,
      based on LC50 level, teflubenzuron had strong ovicidal activity (LC50 = 0.056 mg
      kg(-1)) followed by pirimiphos-methyl (1.82 mg kg(-1)) and pyriproxyfen (91.9 mg
      kg(-1)). The residual activity data showed that none of the IGRs tested had
      strong activity when applied at 200 mg kg(-1) in reducing the oviposition rates
      of C maculatus at various storage intervals up to 8 months post-treatment.
      However, teflubenzuron reduced adult emergence (F1 progeny), achieving control
      ranging from 96.2% at 1 month to 94.3% at 8 months. Hexaflumuron showed a similar
      trend in its residual activity, ranging between 93.8% control at 1 month to 88.2%
      control at 8 months post-treatment. However, pyriproxyfen was more active than
      the CSIs tested and caused complete suppression (100% control) of adult emergence
      at all storage intervals. Unlike the IGRs tested, pirimiphos-methyl applied at 25
      mg kg(-1) was more effective in reducing oviposition rates of C maculatus up to 8
      months post-treatment. A strong reduction of adult emergence was also observed at
      various bimonthly intervals (98.6% control at 1 month to 91.6% control at 8
      months post-treatment). The persistence of hexaflumuron and pirimiphos-methyl in
      cowpea seeds was also studied over a period of 8 months. The loss of hexaflumuron
      residue in treated cowpeas (200 mg kg(-1)) was very slow during the first month
      post-treatment (4.43%). At the end of 8 months, the residue level had declined
      significantly to 46.4% of the initial applied rate. The loss of pirimiphos-methyl
      residue in treated cowpeas (25 mg kg(-1)) was relatively high during the first
      month post-treatment (36.7%) and increased to 81.6% after 8 months.

PMID- 14727747
TI  - Intensity modulated radiation therapy using laser-accelerated protons: a Monte
      Carlo dosimetric study.
AB  - In this paper we present Monte Carlo studies of intensity modulated radiation
      therapy using laser-accelerated proton beams. Laser-accelerated protons coming
      out of a solid high-density target have broad energy and angular spectra leading
      to dose distributions that cannot be directly used for therapeutic applications.
      Through the introduction of a spectrometer-like particle selection system that
      delivers small pencil beams of protons with desired energy spectra it is feasible
      to use laser-accelerated protons for intensity modulated radiotherapy. The method
      presented in this paper is a three-dimensional modulation in which the proton
      energy spectrum and intensity of each individual beamlet are modulated to yield a
      homogeneous dose in both the longitudinal and lateral directions. As an
      evaluation of the efficacy of this method, it has been applied to two prostate
      cases using a variety of beam arrangements. We have performed a comparison study
      between intensity modulated photon plans and those for laser-accelerated protons.
      For identical beam arrangements and the same optimization parameters, proton
      plans exhibit superior coverage of the target and sparing of neighbouring
      critical structures. Dose-volume histogram analysis of the resulting dose
      distributions shows up to 50% reduction of dose to the critical structures. As
      the number of fields is decreased, the proton modality exhibits a better
      preservation of the optimization requirements on the target and critical
      structures. It is shown that for a two-beam arrangement (parallel-opposed) it is
      possible to achieve both superior target coverage with 5% dose inhomogeneity
      within the target and excellent sparing of surrounding tissue.

PMID- 14727748
TI  - A simulation model for analysing brain structure deformations.
AB  - Recent developments of medical software applications--from the simulation to the
      planning of surgical operations--have revealed the need for modelling human
      tissues and organs, not only from a geometric point of view but also from a
      physical one, i.e. soft tissues, rigid body, viscoelasticity, etc. This has given
      rise to the term 'deformable objects', which refers to objects with a morphology,
      a physical and a mechanical behaviour of their own and that reflects their
      natural properties. In this paper, we propose a model, based upon physical laws,
      suitable for the realistic manipulation of geometric reconstructions of
      volumetric data taken from MR and CT scans. In particular, a physically based
      model of the brain is presented that is able to simulate the evolution of
      different nature pathological intra-cranial phenomena such as haemorrhages,
      neoplasm, haematoma, etc and to describe the consequences that are caused by
      their volume expansions and the influences they have on the anatomical and neuro
      functional structures of the brain.

PMID- 14727749
TI  - A methodology for generating normal and pathological brain perfusion SPECT images
      for evaluation of MRI/SPECT fusion methods: application in epilepsy.
AB  - Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in
      particular pathological datasets is difficult, due to the frequent lack of
      relevant ground truth. We propose a methodology to generate MRI and SPECT
      datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate
      the method when dealing with ictal SPECT. The method consists in generating
      normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1
      weighted MRI using realistic Monte Carlo simulations that closely reproduce the
      response of a SPECT imaging system. Anatomical input data for the SPECT
      simulations are obtained from this 3D T1-weighted MRI, while functional input
      data result from an inter-individual analysis of anatomically standardized SPECT
      data. The method makes it possible to control the 'brain perfusion' function by
      proposing a theoretical model of brain perfusion from measurements performed on
      real SPECT images. Our method provides an absolute gold standard for assessing
      MRI/SPECT registration method accuracy since, by construction, the SPECT data are
      perfectly registered with the MRI data. The proposed methodology has been applied
      to create a theoretical model of normal brain perfusion and ictal brain perfusion
      characteristic of mesial temporal lobe epilepsy. To approach realistic and
      unbiased perfusion models, real SPECT data were corrected for uniform
      attenuation, scatter and partial volume effect. An anatomic standardization was
      used to account for anatomic variability between subjects. Realistic simulations
      of normal and ictal SPECT deduced from these perfusion models are presented. The
      comparison of real and simulated SPECT images showed relative differences in
      regional activity concentration of less than 20% in most anatomical structures,
      for both normal and ictal data, suggesting realistic models of perfusion
      distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients
      measured on simulated data were found within the range of asymmetry coefficients
      measured on corresponding real data. The features of the proposed approach are
      compared with those of other methods previously described to obtain datasets
      appropriate for the assessment of fusion methods.

PMID- 14727750
TI  - Development and validation of a BEAMnrc component module for accurate Monte Carlo
      modelling of the Varian dynamic Millennium multileaf collimator.
AB  - A new component module (CM), designated DYNVMLC, was developed to fully model the
      geometry of the Varian Millennium 120 leaf collimator using the BEAMnrc Monte
      Carlo code. The model includes details such as the leaf driving screw hole,
      support railing groove and leaf tips. Further modifications also allow sampling
      of leaf sequence files to simulate the movement of the multileaf collimator (MLC)
      leaves during an intensity modulated radiation therapy (IMRT) delivery. As an
      initial validation of the code, the individual leaf geometries were visualized by
      tracing particles through the component module and recording their position each
      time a leaf boundary was crossed. A model of the Varian CL21EX linear accelerator
      6 MV photon beam incorporating the new CM was built with the BEAMnrc user code.
      The leaf material density and abutting leaf air gap were chosen to match
      simulated leaf leakage profiles with film measurements in a solid water phantom.
      Simulated depth dose and off-axis profiles for a variety of MLC defined static
      fields agreed to within 2% with ion chamber and diode measurements in a water
      phantom. Simulated dose distributions for IMRT intensity patterns delivered using
      both static and dynamic techniques were found to agree with film measurements to
      within 4%. A comparison of interleaf leakage profiles for the new CM and an
      equivalent leaf model using the existing VARMLC CM demonstrated that the
      simplified geometry of VARMLC is not able to accurately predict the details of
      the MLC leakage for the 120 leaf collimator.

PMID- 14727751
TI  - Optimization of beam orientations and beam weights for conformal radiotherapy
      using mixed integer programming.
AB  - An algorithm for optimizing beam orientations and beam weights for conformal
      radiotherapy has been developed. The algorithm models the optimization of beam
      orientations and beam weights as a problem of mixed integer linear programming
      (MILP), and optimizes the beam orientations and beam weights simultaneously. The
      application process of the algorithm has four steps: (a) prepare a pool of beam
      orientation candidates with the consideration of avoiding any patient-gantry
      collision and avoiding direct irradiation of organs at risk with quite low
      tolerances (e.g., eyes). (b) Represent each beam orientation candidate with a
      binary variable, and each beam weight with a continuous variable. (c) Set up an
      optimization problem according to dose prescriptions and the maximum allowed
      number of beam orientations. (d) Solve the optimization problem with a ready-to
      use MILP solver. After optimization, the candidates with unity binary variables
      remain in the final beam configuration. The performance of the algorithm was
      tested with clinical cases. Compared with standard treatment plans, the beam
      orientation-optimized plans had better dose distributions in terms of target
      coverage and avoidance of critical structures. The optimization processes took
      less than 1 h on a PC with a Pentium IV 2.4 GHz processor.

PMID- 14727752
TI  - Treatment planning for prostate brachytherapy using region of interest adjoint
      functions and a greedy heuristic.
AB  - We have developed an efficient treatment-planning algorithm for prostate implants
      that is based on region of interest (ROI) adjoint functions and a greedy
      heuristic. For this work, we define the adjoint function for an ROI as the
      sensitivity of the average dose in the ROI to a unit-strength brachytherapy
      source at any seed position. The greedy heuristic uses a ratio of target and
      critical structure adjoint functions to rank seed positions according to their
      ability to irradiate the target ROI while sparing critical structure ROIs. This
      ratio is computed once for each seed position prior to the optimization process.
      Optimization is performed by a greedy heuristic that selects seed positions
      according to their ratio values. With this method, clinically acceptable
      treatment plans are obtained in less than 2 s. For comparison, a branch-and-bound
      method to solve a mixed integer-programming model took more than 50 min to arrive
      at a feasible solution. Both methods achieved good treatment plans, but the
      speedup provided by the greedy heuristic was a factor of approximately 1500. This
      attribute makes this algorithm suitable for intra-operative real-time treatment
      planning.

PMID- 14727753
TI  - The wall correction factor for a spherical ionization chamber used in
      brachytherapy source calibration.
AB  - The effect of wall chamber attenuation and scattering is one of the most
      important corrections that must be determined when the linear interpolation
      method between two calibration factors of an ionization chamber is used. For
      spherical ionization chambers the corresponding correction factors A(w) have to
      be determined by a non-linear trend of the response as a function of the wall
      thickness. The Monte Carlo and experimental data here reported show that the A(w)
      factors obtained for an Exradin A4 chamber, used in the brachytherapy source
      calibration, in terms of reference air kerma rate, are up to 1.2% greater than
      the values obtained by the linear extrapolation method for the studied beam
      qualities. Using the Aw factors derived from Monte Carlo calculations, the
      accuracy of the calibration factor N(K,Ir) for the Exradin A4, obtained by the
      interpolation between two calibration factors, improves about 0.6%. The
      discrepancy between the new calculated factor and that obtained using the
      complete calibration curve of the ion-chamber and the 192Ir spectrum is only
      0.1%.

PMID- 14727754
TI  - The use of a Leksell-BRW adapter for linac radiosurgery as an adjunct to Gamma
      Knife treatment.
AB  - We have investigated the use of an adapter that permits the use of a Leksell
      coordinate frame with a linear accelerator stereotactic radiosurgery system based
      on the Brown-Robert-Wells (BRW) design. This device is useful when lesions that
      are planned for treatment on a Leksell Gamma Knife system are found to be
      inaccessible to the Gamma Knife. We have found that with this device objects
      within a head phantom can be targeted by the linear accelerator within an
      accuracy of approximately 1 mm.

PMID- 14727755
TI  - Dosimetry of ultrasoft x-rays (1.5 keV Al(Kalpha)) using radiochromatic films and
      colour scanners.
AB  - This work explores the possibility of measuring the absorbed dose of ultrasoft x
      rays (USX, 1.5 keV Al(Kalpha)) with GAFCHROMIC HD-810 radiochromatic dosimetry
      films (HD-810 films) and colour scanners. HD-810 films were exposed to USX, soft
      x-rays (14.8 keV) and gamma-rays (60Co) for various times. The response of HD-810
      films to absorbed doses of gamma-rays in water was calibrated with Fricke
      dosimetry and used for the calibration of USX. The optical density of the HD-810
      films was quantified with an HP ScanJet 6100C scanner and Corel Picture Paint 7.
      The choice of the reading channel and colour adjustment settings were optimized
      to either improve sensitivity or expand the measurable dose range. The response
      of the HD-810 films to the absorbed dose in water decreased by 50% when the
      effective photon energy decreased from 1.25 MeV to 14.8 keV. The ratio of the
      mass energy absorption coefficient of the active layer of HD-810 films to that of
      water was found to play a major role in this decrease. The mean absorbed doses of
      the active layer of the HD-810 films exposed to USX were derived. The calculation
      of the initial photon fluence rate and the mean absorbed doses of USX to
      biological samples such as plasmid DNA is discussed. This study suggests that
      radiochromatic dosimetry films are promising secondary dosimeters for measuring
      the absorbed dose of USX.

PMID- 14727756
TI  - Theoretical analysis of the heat convection coefficient in large vessels and the
      significance for thermal ablative therapies.
AB  - Ablative therapies such as radio-frequency (RF) ablation are increasingly used
      for treatment of tumours in liver and other organs. Often large vessels limit the
      extent of the thermal lesion, and cancer cells close to the vessel survive
      resulting in local tumour recurrence. Accurate estimates of the heat convection
      coefficient h for large vessels will help improve ablation techniques, and are
      required for estimation of thermal lesion dimensions in simulations. Previous
      estimates of h did not consider that only part of the vessel is heated, and
      assumed uniform temperature distribution at the vessel wall. An analytical
      relationship between the heat convection coefficient, blood velocity and
      temperature is formulated. The heat convection coefficient evaluated will assist
      both simulations and design of proper protocols for in vivo measurements. The
      mathematical model developed in this work describes the exchange of heat between
      a solid surface and a moving fluid and it is based on energy and motion equations
      for Navier-Stokes fluids. A particular case of a laminar blood flow in the portal
      vein is studied when a portion of its surface is heated. The results show that
      heating a larger portion of the vessels reduces convective heat loss, which may
      result in more effective ablation strategies.

PMID- 14727757
TI  - Measurement of fluorophore concentrations and fluorescence quantum yield in
      tissue-simulating phantoms using three diffusion models of steady-state spatially
      resolved fluorescence.
AB  - Steady-state diffusion theory models of fluorescence in tissue have been
      investigated for recovering fluorophore concentrations and fluorescence quantum
      yield. Spatially resolved fluorescence, excitation and emission reflectance Carlo
      simulations, and measured using a multi-fibre probe on tissue-simulating phantoms
      containing either aluminium phthalocyanine tetrasulfonate (AlPcS4), Photofrin
      meso-tetra-(4-sulfonatophenyl)-porphine dihydrochloride The accuracy of the
      fluorophore concentration and fluorescence quantum yield recovered by three
      different models of spatially resolved fluorescence were compared. The models
      were based on: (a) weighted difference of the excitation and emission
      reflectance, (b) fluorescence due to a point excitation source or (c)
      fluorescence due to a pencil beam excitation source. When literature values for
      the fluorescence quantum yield were used for each of the fluorophores, the
      fluorophore absorption coefficient (and hence concentration) at the excitation
      wavelength (mu(a,x,f)) was recovered with a root-mean-square accuracy of 11.4%
      using the point source model of fluorescence and 8.0% using the more complicated
      pencil beam excitation model. The accuracy was calculated over a broad range of
      optical properties and fluorophore concentrations. The weighted difference of
      reflectance model performed poorly, with a root-mean-square error in
      concentration of about 50%. Monte Carlo simulations suggest that there are some
      situations where the weighted difference of reflectance is as accurate as the
      other two models, although this was not confirmed experimentally. Estimates of
      the fluorescence quantum yield in multiple scattering media were also made by
      determining mu(a,x,f) independently from the fitted absorption spectrum and
      applying the various diffusion theory models. The fluorescence quantum yields for
      AlPcS4 and TPPS4 were calculated to be 0.59 +/- 0.03 and 0.121 +/- 0.001
      respectively using the point source model, and 0.63 +/- 0.03 and 0.129 +/- 0.002
      using the pencil beam excitation model. These results are consistent with
      published values.

PMID- 14727758
TI  - Simulation of a plane wavefront propagating in cardiac tissue using a cellular
      automata model.
AB  - We present a detailed description of a cellular automata model for the
      propagation of action potential in a planar cardiac tissue, which is very fast
      and easy to use. The model incorporates anisotropy in the electrical conductivity
      and a spatial variation of the refractory time. The transmembrane potential
      distribution is directly derived from the cell states, and the intracellular and
      extracellular potential distributions are calculated for the particular case of a
      plane wavefront. Once the potential distributions are known, the associated
      current densities are calculated by Ohm's law, and the magnetic field is
      determined at a plane parallel to the cardiac tissue by applying the law of Biot
      and Savart. The results obtained for propagation speed and for magnetic field
      amplitude with the cellular automata model are compared with values predicted by
      the bidomain formulation, for various angles between wavefront propagation and
      fibre direction, characterizing excellent agreement between the models.

PMID- 14727759
TI  - Determination of complex refractive index of polystyrene microspheres from 370 to
      1610 nm.
AB  - We introduce an inverse method for determining simultaneously the real and
      imaginary refractive indices of microspheres based on integrating sphere
      measurements of diffuse reflectance and transmittance, and Monte Carlo modelling
      in conjunction with the Mie theory. The results for polystyrene microspheres
      suspended in water are presented.

PMID- 14727760
TI  - A flat-panel detector based micro-CT system: performance evaluation for small
      animal imaging.
AB  - A dedicated small-animal x-ray micro computed tomography (micro-CT) system has
      been developed to screen laboratory small animals such as mice and rats. The
      micro-CT system consists of an indirect-detection flat-panel x-ray detector with
      a field-of-view of 120 x 120 mm2, a microfocus x-ray source, a rotational subject
      holder and a parallel data processing system. The flat-panel detector is based on
      a matrix-addressed photodiode array fabricated by a CMOS (complementary metal
      oxide semiconductor) process coupled to a CsI:T1 (thallium-doped caesium iodide)
      scintillator as an x-ray-to-light converter. Principal imaging performances of
      the micro-CT system have been evaluated in terms of image uniformity, voxel noise
      and spatial resolution. It has been found that the image non-uniformity mainly
      comes from the structural non-uniform sensitivity pattern of the flat-panel
      detector and the voxel noise is about 48 CT numbers at the voxel size of 100 x
      100 x 200 microm3 and the air kerma of 286 mGy. When the magnification ratio is
      2, the spatial resolution of the micro-CT system is about 14 1p/mm (line pairs
      per millimetre) that is almost determined by the flat-panel detector showing
      about 7 1p/mm resolving power. Through low-contrast phantom imaging studies, the
      minimum resolvable contrast has been found to be less than 36 CT numbers at the
      air kerma of 95 mGy. Some laboratory rat imaging results are presented.

PMID- 14727761
TI  - Analysis of diffusion tensor magnetic resonance imaging data using principal
      component analysis.
AB  - An analysis method for diffusion tensor (DT) magnetic resonance imaging data is
      described, which, contrary to the standard method (multivariate fitting), does
      not require a specific functional model for diffusion-weighted (DW) signals. The
      method uses principal component analysis (PCA) under the assumption of a single
      fibre per pixel. PCA and the standard method were compared using simulations and
      human brain data. The two methods were equivalent in determining fibre
      orientation. PCA-derived fractional anisotropy and DT relative anisotropy had
      similar signal-to-noise ratio (SNR) and dependence on fibre shape. PCA-derived
      mean diffusivity had similar SNR to the respective DT scalar, and it depended on
      fibre anisotropy. Appropriate scaling of the PCA measures resulted in very good
      agreement between PCA and DT maps. In conclusion, the assumption of a specific
      functional model for DW signals is not necessary for characterization of
      anisotropic diffusion in a single fibre.

PMID- 14727762
TI  - Modification of functional properties of egg-white proteins.
AB  - Egg-white proteins are extensively utilised as food ingredients due to their
      unique functional properties. Several attempts have been made in order to improve
      the functional properties of egg-white proteins and to identify the optimal
      formulations for unique food products. Experimental data proves that controlled
      denaturation of egg-white proteins can have a beneficial impact on various
      functional applications in the food industry such as emulsifying ability, heat
      stability, and gelation. This review describes the effect of heat-induced
      denaturation on protein structure and functionality. Studies on the impact of
      Maillard reaction, which aim to elucidate the structure-function relationship of
      egg-white proteins, are presented. A novel approach which could be the basis for
      the development of new methods aiming to improve the functional properties of egg
      white proteins is also discussed.

PMID- 14727763
TI  - Incidence of aflatoxin B1 in the Egyptian cured meat basterma and control by
      gamma-irradiation.
AB  - In the present studies trials have been carried out to investigate the occurrence
      of aflatoxin B1 in the Egyptian cured meat basterma and to control such
      contamination by gamma-rays. Basterma was prepared from fresh salted meat coated
      with spice paste and stored at room temperature. The total mould counts of
      basterma samples varied from 10(3) to 10(6) cfu/g in summer months and from 10(2)
      to 10(5) cfu/g in winter months. Aspergillus, Penicillium, Mucor, Rhizopus,
      Fusarium and Cladosporium were the most common fungal genera isolated from
      basterma samples and its components. Basterma samples contained total aflatoxins
      at levels from 2.8 to 47 microg x kg(-1). Aflatoxins were determined in the spice
      paste at levels from 9.6 to 120 microg x kg(-1) and in pepper (285.6 microg x kg(
      1)), garlic (224.4 microg x kg(-1)), fenugreek (194.2 microg x kg(-1)), coriander
      (16 and capsicum (42.4 microg x kg(-1)). At an irradiation dose level of 3 kGy,
      only one sample each of pepper, fenugreek, and spice paste were contaminated with
      aflatoxins and all basterma samples and its components were free from aflatoxins
      at an irradiation dose level of 5 kGy.

PMID- 14727764
TI  - Effect of paracasein degradation on sensory properties of Gouda cheese.
AB  - The relation between the sensory quality of Gouda cheese and the extent of
      paracasein degradation, i. e., the content of soluble N, peptide N, amino acid N
      and amine N, was studied. The above-mentioned parameters of paracasein
      degradation differently determined the sensory properties of Gouda cheese. The
      flavour of cheese after 6-week ripening depended to the largest extent on the
      content of amine N and soluble N. The effect of the content of peptide N on
      cheese flavour was smaller but statistically significant. Also the smell of Gouda
      cheese was to the largest extent correlated to the content of amine N. A
      dependence between smell and the content of peptide N was found only in the
      cheeses after 4-week ripening. None of the sensory quality parameters of the
      examined cheeses depended on the content of amino acid N.

PMID- 14727765
TI  - Effect of calcium ions on the solubility of muscular collagen and tenderness of
      beef meat.
AB  - The aim of the present study was to determine the effect of aqueous solutions of
      calcium chloride and calcium lactate on the solubility of beef collagen in raw
      and cooked meat. The content of total collagen, water- and acetic acid-soluble
      collagen and insoluble collagen was determined in beef samples. Shearing force
      was measured after heat treatment. It was found that calcium ions had no
      significant effect on the solubility of muscular collagen. An improvement in beef
      tenderness (27%-34%) caused by calcium ions did not result from breaking of the
      native structure of muscular collagen.

PMID- 14727766
TI  - Changes in chemical composition during development of grass pea (Lathyrus sativus
      L.) seeds.
AB  - The level of chemical components was determined in seeds of grass pea (Lathyrus
      sativus L.), cv. Krab, harvested at a dry matter content between 25.9 and 49.6
      g/100 g of the raw material, and divided into five degrees of maturity. The
      results presented suggest that, in general, with an increasing maturity of seeds,
      the level of the following components increased if related to fresh matter:
      starch, dietary fibre, acids, total and protein nitrogen, total amino acids and
      sulphur amino acids, ash and its alkalinity, magnesium, calcium, total phosphorus
      and phytic phosphorus, and thiamine. The following components were reduced:
      vitamin C, riboflavin, carotenoids, beta-carotene, and chlorophylls. No such
      regularity could be found with respect to the accumulation of sugars, essential
      amino acids, and iron. By expressing the results in dry matter, increases were
      noted in starch, protein nitrogen, and thiamine. The content of sugars, total
      nitrogen, total amino acids, essential and sulphur amino acids, ash and its
      alkalinity, magnesium, phosphorus, vitamin C, riboflavin, carotenoids, beta
      carotene, and chlorophylls were reduced while that of dietary fibre, iron,
      calcium, and phytic phosphorus varied.

PMID- 14727767
TI  - Effect of the volatile constituents isolated from Thymus albicans, Th.
      mastichina, Th. carnosus and Thymbra capitata in sunflower oil.
AB  - The composition of essential oils isolated from Thymus albicans and Thymbra
      capitata collected in Algarve (Portugal), Th. mastichina collected in Algarve and
      Estremadura (Portugal) and Th. carnosus also collected in Algarve, during the
      flowering phase, was analysed by gas chromatography (GC) and GC coupled to mass
      spectrometry (GC-MS). The antioxidant capacity of the oils as well as some of
      their main components was determined by periodic evaluation of the peroxide
      values in sunflower oils stored at 60 degrees C. These peroxide values were
      compared to that of butylated hydroxytoluene (BHT) and control (without adding
      antioxidants) under the same experimental conditions. The oils of Th. albicans
      and Th. mastichina, collected in Algarve, were dominated by 1,8-cineole (68% and
      45%, respectively), whereas linalool (52%) was the main component from the oils
      isolated from Th. mastichina collected in Estremadura. Carvacrol (68%) was the
      major component present in the oils of Thymbra capitata while borneol (18%),
      terpinen-4-ol (11%) and camphene (9%) were the major ones in the essential oil of
      Th. carnosus. The essential oils as well as some of their main components showed
      higher antioxidant capacity than that of the synthetic antioxidant BHT. At the
      end of the experiment (57 days), BHT showed a percentage of inhibition of 20%,
      while that of the essential oils ranged from 46% for Th. carnosus, to 59% for Th.
      mastichina collected in Estremadura.

PMID- 14727768
TI  - Fluorometric determination of chemically available lysine: adaptation, validation
      and application to different milk products.
AB  - A spectrophotometric method based on the reaction between available lysine and
      ortho-phthaldialdehyde (OPA) was adapted and validated for fluorometric
      determination of the chemically available lysine contents in milk matrices (UHT
      and conventional in-bottle sterilized cow milk, milk-based infant formulas and
      infant formula ingredients). The values of the analytical parameters show its
      usefulness as a routine method (linearity, r = 0.9992; detection limit, 0.0066
      mg/mL assay; accuracy, 99-108%; precision, intra-day 2.1-5.9% and inter-day 3.5
      10.2%). No statistically significant differences (p < 0.05) were found between
      the values obtained with the adapted method and those obtained applying the 1
      fluoro-2,4-dinitrobenzene (FDNB) (Carpenter) technique. The OPA method was used
      to measure the chemically available lysine contents in UHT and sterilized milk
      marketed in Spain, to study the evolution of chemically available lysine during
      the shelf-life of UHT milks, and finally the quality of name- and store-brand UHT
      milks was also compared. No statistically significant differences (p < 0.05) were
      found between either the available lysine contents of the same type of UHT or
      sterilized milk or between store- and name-brand UHT milks. Statistically
      significant differences (p < 0.05) were found between the chemically available
      lysine contents in UHT and sterilized milk. Losses of chemically available lysine
      ranging from 2.7 to 29% were obtained during the shelf-life of UHT milk.

PMID- 14727769
TI  - In vitro influence of spices and spice-active principles on digestive enzymes of
      rat pancreas and small intestine.
AB  - In vitro influence of 14 individual spices (curcumin, capsaicin, piperine,
      garlic, onion, ginger, mint, coriander, cumin, ajowan, fennel, fenugreek,
      mustard, and asafoetida) on the activities of digestive enzymes of rat pancreas
      and small intestine was examined by including them in the reaction mixture at two
      different concentrations. A majority of spices enhanced the activity of
      pancreatic lipase and amylase when they are directly in contact with the enzyme.
      It is inferred that this positive influence on the activity of enzymes may have a
      supplementary role in the overall digestive stimulant action of spices, besides
      causing an enhancement of the titres of digestive enzymes in pancreatic tissue.

PMID- 14727770
TI  - Quality of cold-pressed edible rapeseed oil in Germany.
AB  - Forty-eight cold-pressed edible rapeseed oils obtained from small- and medium
      sized decentralized plants located all over Germany were characterized by
      different chemical parameters for their composition and by descriptive sensory
      evaluation. Between the different oils great differences could be noticed for
      each parameter. The results evidenced that additionally to the features given in
      the Guidelines for edible fats and oils of the German Food Codex, especially the
      sensory evaluation, the oxidation stability (Rancimat), content and the
      composition of tocopherols, the content of trans-fatty acids and the content of
      steradienes were crucial parameters to guarantee a high-quality product for the
      consumer.

PMID- 14727771
TI  - An update on the processing of high-protein rice products.
AB  - The component of protein in rice, at 7-9% by weight, is relatively low, but the
      total amount of rice protein potentially available is significant because the
      production of rice worldwide, at 380 million tons annually, is huge. Rice
      proteins are recognized as nutritional, hypoallergenic, and healthy for human
      consumption, and rice protein products have been in demand in recent years.
      However, because of difficulties in the processing, rice protein products,
      particularly high-protein content ones, have not been readily available. Two of
      the main sources of rice protein, rice bran and, to a lesser extent, broken rice
      kernels, have been under-used and under-priced. This report provides an update on
      the processing of these sources for rice proteins. Methods of protein processing
      are highlighted including the traditional alkaline extraction, enzyme-assisted
      extraction, and the novel uses of physical treatment prior to water extraction.
      Also discussed are effects of processing on the functional and nutritional
      properties of rice protein.

PMID- 14727772
TI  - Fractionation, solubility and functional properties of wheat bran proteins as
      influenced by pH and/or salt concentration.
AB  - The content, fractionation, solubility and functional properties of wheat bran
      proteins as well as the effects of pH and/or NaCl concentration on some of these
      functional properties were investigated. The protein content of the bran was
      found to be 16.80%. Albumin and glutelin are the major fractions of wheat bran
      proteins. The minimal protein solubility was observed at pH 5.5, the maximum at
      pH 11.5. The emulsifying capacity, activity and emulsion stability as well as
      foaming capacity and foam stability were greatly affected by pH and salt
      concentrations. Lower values were observed at acidic pH and high salt
      concentration. The least gelation concentration of wheat bran proteins was found
      to be 16% when the proteins were dissolved in 1.0 M NaCl. The total protein was
      highly viscous and dispersable with water-holding capacity of 4.20 mL H2O/g
      protein, oil-holding capacity of 1.70 mL oil/g protein and bulk density of 0.29
      g/mL while dispensability was found to be 77.30%.

PMID- 14727773
TI  - Determination of glutathione peroxidase activity in human milk.
AB  - An analytical method for determining glutathione peroxidase (GPx) (EC 1.11.1.9)
      activity in whole blood has been adapted to human milk samples. The values
      obtained for precision (relative standard deviation: 8.4%), linearity and
      accuracy (recovery: 90.4%) indicate the adequacy of the method for the mentioned
      purpose. The method was applied to 11 human milk samples obtained in the range
      from 6 to 135 days post partum. The resulting GPx activities (83.3 +/- 23.6 U/L)
      did not correlate to the selenium content of the samples, though a reciprocal
      correlation was found between the duration of lactation and milk GPx activity.

PMID- 14727774
TI  - 2,2-diphenyl-1-picrylhydrazyl (DPPH*) test demonstrates antiradical activity of
      Dorstenia psilurus and Dorstenia ciliata plant extracts.
AB  - Plants of the Dorstenia genus, used in traditional medicine and as food
      ingredient in Africa, are rich in polyphenolic compounds which can be involved in
      prevention of disease and food spoilage through their antioxidant activity. The
      antiradical activities of extracts of Dorstenia psilurus. D. ciliata and a
      phenolic compound (6-prenylapigenin) from D. ciliata were evaluated with the 2,2
      diphenyl-1-picrylhydrazyl (DPPH*) test. D. psilurus chloroform and D. ciliata
      ethyl acetate extracts were shown to exhibit antiradical activities, with slow
      kinetic action. The efficient concentrations at different kinetic times "EC50,t"
      for the D. ciliata extract: 699, 479, 311 and 251 g/kg after 30, 60, 120 and 180
      min, respectively, were always much lower than for the D. psilurus extract: 2341,
      2312, 1672 and 1281 g/kg at the same times. The antiradical activity of 6
      prenylapigenin was weak compared to the extracts. These results suggest the
      antioxidant activities of Dorstenia extracts and might help to understand their
      traditional use. We propose "EC50, t", calculated on the curves obtained with
      DPPH test, as a parameter to screen and compare antiradical activities of plant
      extracts with slow kinetic behaviour.

PMID- 14727775
TI  - Bioaccessibility of calcium, iron and zinc from three legume samples.
AB  - Legumes can be a source of mineral elements but also of antinutritional factors
      which can affect their absorption. An in vitro method including gastrointestinal
      digestion was used to estimate mineral bioavailability. Soluble (bioaccessible)
      and insoluble calcium, iron and zinc from white beans, chickpeas and lentils were
      determined after gastrointestinal digestion. The influence of the original sample
      weight on the soluble mineral fraction was also estimated. The results obtained
      show that white beans are the legumes with the highest bioaccessible calcium and
      iron contents. Lentils have a high iron content but its bioaccessibility is much
      lower than that of iron from white beans and chickpeas. An increase in sample
      weight increases the amount of bioaccessible element available for intake, but
      the increase is not always proportional.

PMID- 14727776
TI  - Changes in phenolic compounds, colour and antioxidant activity in industrial red
      myrtle liqueurs during storage.
AB  - The results of a study on the evolution of phenolic compounds, colour and
      antioxidant activity in two industrial red myrtle liqueurs during storage in
      bottles under different bottle headspace (constant or increasing) and exposure to
      light are reported. In the year of the study, the phenolic compounds showed
      considerable changes even in the liqueurs stored with constant headspace. The
      anthocyanins in particular, both free and combined, tended to decrease. As
      expected, the same phenomena were observed in an accelerated form in the product
      stored in bottles with increasing headspace. The colour, evaluated according to
      the classic spectrophotometric parameters of intensity and hue, showed marked
      variability, especially in samples in which headspace was progressively
      increased. The two liqueurs showed antioxidant capacity values, expressed as mM
      of Trolox, comparable to those of red wine. They significantly decreased during
      storage in the bottles with increasing headspace, while values remained almost
      constant in the others.

PMID- 14727777
TI  - Measuring quality in modern managed care.

PMID- 14727778
TI  - Special issues, special sections--special consideration?

PMID- 14727779
TI  - Was breast conserving surgery underutilized for early stage breast cancer?
      Instrumental variables evidence for stage II patients from Iowa.
AB  - OBJECTIVE: To estimate the average survival effects of breast conserving surgery
      plus irradiation relative to mastectomy for marginal stage II breast cancer
      patients in Iowa from 1989-1994. DATA SOURCES/DATA SETTING: Secondary linked Iowa
      SEER Cancer Registry--Iowa Hospital Association discharge abstract data for women
      in Iowa with stage II breast cancer from 1989-1994. STUDY DESIGN: Observational
      instrumental variables (IV) analysis. DATA COLLECTION/EXTRACTION METHODS: Women
      with stage II breast cancer from the Iowa SEER Cancer Registry 1989-1994 who
      received all of their inpatient care in Iowa were linked with their respective
      hospital discharge abstracts. PRINCIPAL FINDINGS: Breast conserving surgery plus
      irradiation decreased survival relative to mastectomy for marginal stage II
      breast cancer patients in Iowa during the early 1990s. In this study marginal
      patients were those whose surgery choices were affected by differences in area
      treatment rates and access to radiation facilities. CONCLUSIONS: If marginal
      patients are representative of patients whose treatment choices would be affected
      by changes in treatment rates, an increase in the breast conserving surgery plus
      irradiation rate for stage II early stage breast cancer patients would have
      decreased survival in Iowa during the early 1990s. Further research with newer
      data and broader samples is needed to make more current and specific assessments.

PMID- 14727780
TI  - Competition, payers, and hospital quality.
AB  - OBJECTIVE: To estimate the effects of competition for both Medicare and HMO
      patients on the quality decisions of hospitals in Southern California. DATA
      SOURCE: Secondary discharge data from the Office of Statewide Health Planning and
      Development for the State of California for the period 1989-1993. STUDY DESIGN:
      Outcome variables are the risk-adjusted hospital mortality rates for pneumonia
      (estimated by the authors) and acute myocardial infarction (AMI) (reported by the
      state of California). Measures of competition are constructed for each hospital
      and payer type. The competition measures are formulated to mitigate the
      possibility of endogeneity bias. The relationships between risk-adjusted
      mortality and the different competition measures are estimated using ordinary
      least squares. PRINCIPAL FINDINGS: The study finds that an increase in the degree
      of competition for health maintenance organization (HMO) patients is associated
      with a decrease in risk-adjusted hospital mortality rates. Conversely, an
      increase in competition for Medicare enrollees is associated with an increase in
      risk-adjusted mortality rates for hospitals. CONCLUSIONS: In conjunction with
      previous research, the estimates indicate that increasing competition for HMO
      patients appears to reduce prices and save lives and hence appears to improve
      welfare. However, increases in competition for Medicare appear to reduce quality
      and may reduce welfare. Increasing competition has little net effect on hospital
      quality in our sample.

PMID- 14727781
TI  - Does aggressive care following acute myocardial infarction reduce mortality?
      Analysis with instrumental variables to compare effectiveness in Canadian and
      United States patient populations.
AB  - BACKGROUND: Previous U.S. studies suggest that the incremental ("marginal") use
      of the aggressive approach to care for acute myocardial infarction (AMI) in
      patients differing only in their distance to hospitals offering aggressive care
      may be associated with small mortality benefits. We hypothesized that the
      marginal benefits should be larger in Canada, as the country is operating on a
      lower margin because the approach to care is more conservative overall. METHODS:
      This retrospective study used administrative data of hospital admissions and
      health services for all patients admitted for a first AMI in Quebec in 1988 (n =
      8,674). We used differential distances to hospitals offering aggressive care as
      instrumental variables when measuring mortality up to four years after AMI.
      RESULTS: Of the 4,422 subjects who were > or = 65 years old, 11 percent received
      cardiac catheterization within 90 days after admission. In a previous study that
      applied similar methodology to the 1987 U.S. Medicare population, 23 percent of
      subjects received catheterization within 90 days. As in the U.S. study, we found
      that subjects living closer to hospitals offering aggressive care were more
      likely to receive aggressive care than subjects living further away (26 percent
      versus 19 percent received cardiac catheterization within 90 days; 95 percent CI:
      5 percent to 9 percent). Unlike the U.S. study, we found no differences in
      mortality across the "close" versus "far" differential distance groups
      (unadjusted differences at one year: 1 percent; 95 percent CI: -1 percent to 3
      percent). This absence of association held in elderly (> or = 65 years) and
      younger age groups. Adjusted results also showed no differences between subjects
      receiving aggressive versus conservative care (at one year: 4 percent; 95 percent
      CI: -11 percent to 20 percent). CONCLUSIONS: Contrary to our hypothesis, but
      consistent with results from numerous randomized trials and observational
      studies, we cannot confirm that, on the margin, the aggressive approach to post
      AMI care is associated with mortality benefits in Canada.

PMID- 14727782
TI  - Mental health services use among school-aged children with disabilities: the role
      of sociodemographics, functional limitations, family burdens, and care
      coordination.
AB  - OBJECTIVE: To examine the use of mental health services and correlates of
      receiving services among community-dwelling children with disabilities, ages 6 to
      17 years. STUDY DESIGN: Data are from the 1994 and 1995 National Health Interview
      Survey Disability Supplements (NHIS-D), conducted by the National Center for
      Health Statistics. The study sample is 4,939 children with disabilities,
      representing an estimated eight million children with disabilities nationwide.
      Parents of children under 16 years of age reported (17-year-olds self-reported)
      on health, emotional and behavioral problems, mental health services use, and
      who, if anyone, coordinated the child's health care. PRINCIPAL FINDINGS: Among
      disabled children with poor psychosocial adjustment (11.5 percent), only 11.8
      percent received mental health services in the past year. Multivariate logistic
      regression analysis showed service use was associated with poor psychosocial
      adjustment; communication, social, and learning-related functional impairments;
      public health insurance; and financial family burdens. Younger and black disabled
      children were less likely to receive mental health services. The odds of service
      use were greater with the involvement of a health professional in coordinating
      care, in contrast to no one or family only. Moreover, children with disabilities
      were more likely to use outpatient mental health services if their care was
      jointly coordinated by a family member and a health professional, compared to a
      health professional working alone. In contrast to inpatient and outpatient care,
      race and family burden were not associated with the likelihood of mental health
      counseling in special education school settings. CONCLUSIONS: Findings indicate
      that only two in five disabled children with poor psychosocial adjustment receive
      mental health services. Differences by age, race, and insurance coverage suggest
      that inequalities to access exist. However, the school setting may be one in
      which some barriers to mental health services for disabled children are reduced.
      The study also shows that the involvement of health professionals in care
      coordination is associated with greater access to mental health care for disabled
      children. These findings underscore the importance of engaging both health care
      professionals and the family in the care process.

PMID- 14727783
TI  - The impact of the prospective payment system for skilled nursing facilities on
      therapy service provision: a transaction cost approach.
AB  - OBJECTIVE: To examine skilled nursing facilities (SNFs) "make-or-buy" decisions
      with respect to rehabilitation therapy service provision in the 1990s, both
      before and after implementation of Medicare's Prospective Payment System (PPS)
      for SNFs. DATA SOURCES: Longitudinal On-line Survey Certification and Reporting
      (OSCAR) data (1992-2001) on a sample of 10,241 freestanding urban SNFs. STUDY
      DESIGN: We estimated a longitudinal multinomial logistic regression model derived
      from transaction cost economic theory to predict the probability of the outcome
      in each of four service provision categories (all employed staff, all contract,
      mixed, and no services provided). PRINCIPAL FINDINGS: Transaction frequency,
      uncertainty, and complexity result in greater control over therapy services
      through employment as opposed to outside contracting. For-profit status and chain
      affiliation were associated with greater control over therapy services. Following
      PPS, nursing homes acted to limit transaction costs by either exiting the
      rehabilitation market or exerting greater control over therapy services by
      managing rehabilitation services in-house. CONCLUSIONS: The financial incentives
      associated with changes in reimbursement methodology have implications that
      extend beyond the boundaries of the health care industry segment directly
      affected. Unintended quality and access consequences need to be carefully
      monitored by the Medicare program.

PMID- 14727785
TI  - Psychometric properties of the Consumer Assessment of Health Plans Study (CAHPS)
      2.0 adult core survey.
AB  - OBJECTIVE: To estimate the reliability and validity of survey measures used to
      evaluate health plans and providers from the consumer's perspective. DATA
      SOURCES: Members (166,074) of 306 U.S. health plans obtained from the National
      CAHPS Benchmarking Database 2.0, a voluntary effort in which sponsors of CAHPS
      surveys contribute data to a common repository. STUDY DESIGN: Members of
      privately insured health plans serving public and private employers across the
      United States were surveyed by mail and telephone. Interitem correlations and
      correlations of items with the composite scores were estimated. Plan-level and
      internal consistency reliability are estimated. Multivariate associations of
      composite measures with global ratings are also examined to assess construct
      validity. Confirmatory factor analysis is used to examine the factor structure of
      the measure. FINDINGS: Plan-level reliability of all CAHPS 2.0 reporting
      composites is high with the given sample sizes. Fewer than 170 responses per plan
      would achieve plan-level reliability of .70 for the five composites. Two of the
      composites display high internal consistency (Cronbach's alpha > or = .75), while
      responses to items in the other three composites were not as internally
      consistent (Cronbach's alpha from .58 to .62). A five-factor model representing
      the CAHPS 2.0 composites fits the data better than alternative two- and three
      factor models. CONCLUSION: Two of the five CAHPS 2.0 reporting composites have
      high internal consistency and plan-level reliability. The other three summary
      measures were reliable at the plan level and approach acceptable levels of
      internal consistency. Some of the items that form the CAHPS 2.0 adult core
      survey, such as the measure of waiting times in the doctor's office, could be
      improved. The five-dimension model of consumer assessments best fits the data
      among the privately insured; therefore, consumer reports using CAHPS surveys
      should provide feedback using five composites.

PMID- 14727784
TI  - Measuring hospital quality: can medicare data substitute for all-payer data?
AB  - OBJECTIVES: To assess whether adverse outcomes in Medicare patients can be used
      as a surrogate for measures from all patients in quality-of-care research using
      administrative datasets. DATA SOURCES: Patient discharge abstracts from state
      data systems for 799 hospitals in 11 states. National MedPAR discharge data for
      Medicare patients from 3,357 hospitals. State hospital staffing surveys or
      financial reports. American Hospital Association Annual Survey. STUDY DESIGN: We
      calculate rates for 10 adverse patient outcomes, examine the correlation between
      all-patient and Medicare rates, and conduct negative binomial regressions of
      counts of adverse outcomes on expected counts, hospital nurse staffing, and other
      variables to compare results using all-patient and Medicare patient data. DATA
      COLLECTION/EXTRACTION: Coding rules were established for eight adverse outcomes
      applicable to medical and surgical patients plus two outcomes applicable only to
      surgical patients. The presence of these outcomes was coded for 3 samples: all
      patients in the 11-state sample, Medicare patients in the 11-state sample, and
      Medicare patients in the national Medicare MedPAR sample. Logistic regression
      models were used to construct estimates of expected counts of the outcomes for
      each hospital. Variables for teaching, metropolitan status, and bed size were
      obtained from the AHA Annual Survey. PRINCIPAL FINDINGS: For medical patients,
      Medicare rates were consistently higher than all-patient rates, but the two were
      highly correlated. Results from regression analysis were consistent across the 11
      state all-patient, 11-state Medicare, and national Medicare samples. For surgery
      patients, Medicare rates were generally higher than all-patient rates, but
      correlations of Medicare and all-patient rates were lower, and regression results
      less consistent. CONCLUSIONS: Analyses of quality of care for medical patients
      using Medicare-only and all-patient data are likely to have similar findings.
      Measures applied to surgery patients must be used with more caution, as those
      tested only in Medicare patients may not provide results comparable to those from
      all-patient samples or across different samples of Medicare patients.

PMID- 14727786
TI  - Measuring the quality of diabetes care using administrative data: is there bias?
AB  - OBJECTIVES: Health care organizations often measure processes of care using only
      administrative data. We assessed whether measuring processes of diabetes care
      using administrative data without medical record data is likely to underdetect
      compliance with accepted standards for certain groups of patients. DATA
      SOURCES/STUDY SETTING: Assessment of quality indicators during 1998 using
      administrative and medical records data for a cohort of 1,335 diabetic patients
      enrolled in three Minnesota health plans. STUDY DESIGN: Cross-sectional
      retrospective study assessing hemoglobin A1c testing, LDL cholesterol testing,
      and retinopathy screening from the two data sources. Analyses examined whether
      patient or clinic characteristics were associated with underdetection of quality
      indicators when administrative data were not supplemented with medical record
      data. DATA COLLECTION/EXTRACTION METHODS: The health plans provided
      administrative data, and trained abstractors collected medical records data.
      PRINCIPAL FINDINGS: Quality indicators that would be identified if administrative
      data were supplemented with medical records data are often not identified using
      administrative data alone. In adjusted analyses, older patients were more likely
      to have hemoglobin A1c testing underdetected in administrative data (compared to
      patients <45 years, OR 2.95, 95 percent CI 1.09 to 7.96 for patients 65 to 74
      years, and OR 4.20, 95 percent CI 1.81 to 9.77 for patients 75 years and older).
      Black patients were more likely than white patients to have retinopathy screening
      underdetected using administrative data (2.57, 95 percent CI 1.16 to 5.70).
      Patients in different health plans also differed in the likelihood of having
      quality indicators underdetected. CONCLUSIONS: Diabetes quality indicators may be
      underdetected more frequently for elderly and black patients and the physicians,
      clinics, and plans who care for such patients when quality measurement is based
      on administrative data alone. This suggests that providers who care for such
      patients may be disproportionately affected by public release of such data or by
      its use in determining the magnitude of financial incentives.

PMID- 14727787
TI  - How robust are health plan quality indicators to data loss? A Monte Carlo
      simulation study of pediatric asthma treatment.
AB  - OBJECTIVES: (1) To test the robustness of a health plan quality indicator (QI)
      for persistent asthma to various forms of data loss and (2) to assess the
      implications of the findings for other health plan quality measures. DATA
      SOURCES/STUDY SETTINGS: Maryland Medicaid fee-for-service (FFS) claims. Children
      with asthma (n = 5,804) were selected from Medicaid enrollment records and
      medical and pharmacy FFS claims filed between June 1996 and December 1997. STUDY
      DESIGN: A variant of a HEDIS measure for treatment of persistent asthma (the
      percent of asthma patients filling two or more rescue medications who also filled
      a controller medication) was selected to test the robustness of proportion-based
      QIs to loss of data. Data loss was simulated through a series of Monte Carlo
      experiments. DATA COLLECTION/EXTRACTION METHODS: Merged FFS medical and
      prescription claims. PRINCIPAL FINDINGS: The asthma QI measure was highly robust
      to systematic and random data loss. The measure declined by less than 2 percent
      in the presence of up to a 35 percent data loss. Redundancy in the numerator of
      the QI significantly increased the robustness of the measure to data loss.
      CONCLUSIONS: A HEDIS-related QI measure for persistent asthma is robust to data
      loss. The findings suggest that other proportion-based quality indicators,
      particularly those in which plan members have multiple opportunities to meet the
      numerator criterion, are likely to reflect true levels of health plan quality in
      the face of incomplete data capture.

PMID- 14727788
TI  - Variability in asthma care and services for low-income populations among practice
      sites in managed Medicaid systems.
AB  - OBJECTIVE: To characterize and describe variability in processes of asthma care
      and services tailored for low-income populations in practice sites participating
      in Medicaid managed care (MMC). STUDY SETTING: Eighty-five practice sites
      affiliated with five not-for-profit organizations participating in managed
      Medicaid (three group-model health maintenance organizations [HMOs] and two
      Medicaid managed care organizations [MCOs]). STUDY DESIGN/DATA COLLECTION: We
      conducted a mail survey of managed care practice site informants using a
      conceptual model that included chronic illness care and services targeting low
      income populations. The survey asked how frequently a number of processes related
      to asthma care occurred at the practice sites (on a scale from "never" to
      "always"). We report mean and standard deviations of item scores and rankings
      relative to other items. We used within-MCO intraclass correlations to assess how
      consistent responses were among practice sites in the same MCO. PRINCIPAL
      FINDINGS: Processes of care related to asthma varied gready in how often practice
      sites reported doing them, with information systems and self-management support
      services ranking lowest. There was also significant variation in the availability
      of services targeting low-income populations, specifically relating to cultural
      diversity, communication, and enrollee empowerment. Very little of the site-to
      site variation was attributable to the MCO. CONCLUSIONS: Our conceptual framework
      provides a means of assessing the provision of chronic illness care for
      vulnerable populations. There is room for improvement in provision of chronic
      asthma care for children in managed Medicaid, particularly in the areas of self
      management support and information systems. The lack of consistency within MCOs
      on many processes of care suggests that care may be driven more at the practice
      site level than the MCO level, which has implications for quality improvement
      efforts.

PMID- 14727789
TI  - Methodological challenges associated with patient responses to follow-up
      longitudinal surveys regarding quality of care.
AB  - OBJECTIVE: To illustrate, using empirical data, methodological challenges
      associated with patient responses to longitudinal surveys regarding the quality
      of process of care and health status, including overall response rate,
      differential response rate, and stability of responses with time. DATA
      SOURCES/STUDY SETTING: Primary patient self-report data were collected from
      30,308 patients in 1996 and 13,438 patients in 1998 as part of a two-year
      longitudinal study of quality of care and health status of patients receiving
      care delivered by 63 physician organizations (physician groups) across three West
      Coast states. STUDY DESIGN: We analyzed longitudinal, observational data
      collected by Pacific Business Group on Health (PBGH) from patients aged 18-70
      using a four-page survey in 1996 and a similar survey in 1998 to assess health
      status, satisfaction, use of services, and self-reported process of care. A
      subset of patients with self-reported chronic disease in the 1996 study received
      an enriched survey in 1998 to more fully detail processes of care for patients
      with chronic disease. DATA COLLECTION/EXTRACTION METHODS: We measured response
      rate overall and separately for patients with chronic disease. Logistic
      regression was used to assess the impact of 1996 predictors on response to the
      follow-up 1998 survey. We compared process of care scores without and with
      nonresponse weights. Additionally, we measured stability of patient responses
      over time using percent agreement and kappa statistics, and examined rates of
      gender inconsistencies reported across the 1996 and 1998 surveys. PRINCIPAL
      FINDINGS: In 1998, response rates were 54 percent overall and 63 percent for
      patients with chronic disease. Patient demographics, health status, use of
      services, and satisfaction with care in 1996 were all significant predictors of
      response in 1998, highlighting the importance of analytic strategies (i.e.,
      application of nonresponse weights) to minimize bias in estimates of care and
      outcomes associated with longitudinal quality of care and health outcome
      analyses. Process of care scores weighted for nonresponse differed from
      unweighted scores (p<.001). Stability of responses across time was moderate, but
      varied by survey item from fair to excellent. CONCLUSIONS: Longitudinal analyses
      involving the collection of data from the same patients at two points in time
      provide opportunities for analysis of relationships between process and outcomes
      of care that cannot occur with cross-sectional data. We present empirical results
      documenting the scope of the problems and discuss options for responding to these
      challenges. With increasing emphasis in the United States on quality reporting
      and use of financial incentives for quality in the health care market, it is
      important to identify and address methodological challenges that potentially
      threaten the validity of quality-of-care assessments.

PMID- 14727790
TI  - Managed care organizational characteristics and health care use among children
      with special health care needs.
AB  - OBJECTIVE: To examine the relationship between features of managed care
      organizations (MCOs) and health care use patterns by children. DATA SOURCES:
      Telephone survey data from 2,223 parents of children with special health care
      needs, MCO-administrator interview data, and health care claims data. STUDY
      DESIGN: Cross-sectional survey data from families about the number of
      consequences of their children's conditions and from MCO administrators about
      their plans' organizational features were used. Indices reflecting the MCO
      characteristics were developed using data reduction techniques. Hierarchical
      models were developed to examine the relationship between child sociodemographic
      and health characteristics and the MCO indices labeled: Pediatrician Focused (PF)
      Index, Specialist Focused (SF) Index, and Fee for Service (FFS) Index, and
      outpatient use rates and charges, inpatient admissions, emergency room (ER)
      visits, and specialty consultations. DATA COLLECTION/EXTRACTION METHODS: The
      telephone and MCO-administrator survey data were linked to the enrollment and
      claims files. PRINCIPAL FINDINGS: The child's age, gender, and condition
      consequences were consistent predictor variables related to health care use and
      charges. The PF Index was associated with decreased outpatient use rates and
      charges and decreased inpatient admissions. The SF Index was associated with
      increased ER visits and decreased specialty consultations, while the FFS Index
      was associated with increased outpatient use rates and charges. CONCLUSION: After
      controlling for sociodemographic and health characteristics, the PF, SF, and FFS
      indices were significantly associated with children's health care use patterns.

PMID- 14727791
TI  - Sampling patients within physician practices and health plans: multistage cluster
      samples in health services research.
AB  - OBJECTIVE: To better inform study design decisions when sampling patients within
      health plans and physician practices with multiple analysis goals. STUDY SETTING:
      Chronic eye care patients within six health plans across the United States. STUDY
      DESIGN: We developed a simulation-based approach for designing multistage
      samples. We created a range of candidate designs, evaluated them with respect to
      multiple sampling goals, investigated their tradeoffs, and identified the design
      that is the best compromise among all goals. This approach recognizes that most
      data collection efforts have multiple competing goals. DATA COLLECTION: We
      constructed a sample frame from all diabetic patients in six health plans with
      evidence of chronic eye disease (glaucoma and retinopathy). PRINCIPAL FINDINGS:
      Simulations of different study designs can uncover efficiency gains as well as
      inform potential tradeoffs among study goals. Simulations enable us to quantify
      these efficiency gains and to draw tradeoff curves. CONCLUSIONS: When designing a
      complex multistage sample it is desirable to explore the tradeoffs between
      competing sampling goals via simulation. Simulations enable us to investigate a
      larger number of candidate designs and are therefore likely to identify more
      efficient designs.

PMID- 14727792
TI  - Guest editors' introduction: in pursuit of the social determinants of health: the
      evolution of health services research.

PMID- 14727794
TI  - Racial segregation and longevity among African Americans: an individual-level
      analysis.
AB  - OBJECTIVE: To test the relationship between racial segregation and mortality
      using a multidimensional questionnaire-based measure of exposure to segregation.
      DATA SOURCES: Data for this analysis come from the National Survey of Black
      Americans (NSBA), a national multistage probability sample of 2,107 African
      Americans (aged 18-101). The NSBA was conducted as a household survey. The NSBA
      was matched with the National Death Index (NDI). STUDY DESIGN: Prospective cohort
      study, where Cox regression analysis was used to examine the effect of baseline
      variables on time to death over a 13-year period. PRINCIPAL FINDINGS: Respondents
      who were exposed to racial segregation were significantly less likely to survive
      the study period after controls for age, health status, and other predictors of
      mortality. CONCLUSION: The results support previous studies linking segregation
      with health outcomes.

PMID- 14727793
TI  - Measuring contextual characteristics for community health.
AB  - OBJECTIVE: To conceptualize and measure community contextual influences on
      population health and health disparities. DATA SOURCES: We use traditional and
      nontraditional secondary sources of data comprising a comprehensive array of
      community characteristics. STUDY DESIGN: Using a consultative process, we
      identify 12 overarching dimensions of contextual characteristics that may affect
      community health, as well as specific subcomponents relating to each dimension.
      DATA COLLECTION: An extensive geocoded library of data indicators relating to
      each dimension and subcomponent for metropolitan areas in the United States is
      assembled. PRINCIPAL FINDINGS: We describe the development of community
      contextual health profiles, present the rationale supporting each of the profile
      dimensions, and provide examples of relevant data sources. CONCLUSIONS: Our
      conceptual framework for community contextual characteristics, including a
      specified set of dimensions and components, can provide practical ways to monitor
      health-related aspects of the economic, social, and physical environments in
      which people live. We suggest several guiding principles useful for understanding
      how aspects of contextual characteristics can affect health and health
      disparities.

PMID- 14727795
TI  - The association between multiple domains of discrimination and self-assessed
      health: a multilevel analysis of Latinos and blacks in four low-income New York
      City neighborhoods.
AB  - OBJECTIVE: This study examines the association between discrimination due to race
      and other attributes (e.g., sex, age) and self-assessed mental and physical
      health among Latinos and blacks. DATA SOURCE: Latino and black adult participants
      (n = 873) identified by random digit dialing were interviewed by telephone in
      four low-income neighborhoods in New York City: the South Bronx, East Harlem,
      Central Harlem, and Bedford-Stuyvesant. STUDY DESIGN: In this cross-sectional
      study, generalized estimating equations were used to fit multilevel multivariable
      models to test the association between discrimination and poor mental and
      physical health while controlling for socioeconomic status, access to health
      care, social support, smoking, and the racial and ethnic composition of each
      neighborhood. PRINCIPAL FINDINGS: Discrimination due to race and discrimination
      due to other attributes were associated with poor self-assessed mental but not
      physical health in separate multivariable models. Persons who experienced
      multiple domains of discrimination had a greater probability of reporting poor
      mental health than persons who experienced no discrimination. CONCLUSIONS:
      Discrimination due to race and other attributes was a significant correlate of
      mental health among Latinos and blacks independent of other accepted determinants
      of health.

PMID- 14727796
TI  - Distributional issues in the analysis of preventable hospitalizations.
AB  - OBJECTIVE: To describe patterns in ambulatory care sensitive (ACS) admissions at
      the zip code level based on zip code demographic and other characteristics. These
      patterns include trends over time, persistence within zip codes over time, and
      variation between and within socioeconomic strata. DATA SOURCES: New York State
      hospital discharge data 1990-1998, U.S. census data 1990, and New York State
      birth records 1990. STUDY DESIGN: Age- and sex-adjusted rates and volumes of ACS
      admissions are calculated at the zip code level. Descriptive statistics are
      analyzed cross-sectionally and over time. Kernel density functions are estimated
      across income strata. Ordinary and quantile regression techniques are used to
      determine the impact of socioeconomic variables on average and extreme values of
      the distribution of ACS admission rates. PRINCIPAL FINDINGS: Ambulatory care
      sensitive admissions rates declined during the study period but in conjunction
      with a greater decline in overall admission rates. Thus, as a percentage of total
      admissions, they actually rose by 4 percent. Ambulatory care sensitive admissions
      are geographically concentrated and rates are highly persistent within zip codes
      over time. Even on a log scale ACS admissions are typically greater and exhibit
      more variability among low-income zip codes. Other variables positively
      associated with ACS admissions are total population, births to unwed mothers (a
      proxy for family structure), black population, Hispanic population, and the
      number of non-ACS admissions. Births to immigrant mothers (a proxy for immigrant
      population) are negatively associated with ACS admissions. CONCLUSIONS: The
      concentration and persistence of ACS admissions point to a chronic,
      geographically limited deficiency of primary ambulatory care in the most
      underserved neighborhoods. Much of the difference in preventable hospitalization
      levels between high- and low-income areas is driven by very high volumes in the
      low-income areas unrelated to population density. New York data suggest that most
      costs from preventable hospitalizations could be saved by focusing on targeted
      neighborhoods. Socioeconomic and area utilization variables play a role in both
      average and extreme values of the rate of preventable hospitalizations at the zip
      code level. Since variables that affect the average volume of preventable
      hospitalizations can change the distribution of that volume, analysis based on
      averages alone may be inadequate. The findings on area demographics and non-ACS
      admissions point to the need to better understand social and cultural issues as
      well as local admitting practice patterns to encourage appropriate and efficient
      use of the health care delivery system.

PMID- 14727797
TI  - On the importance of age-adjustment methods in ecological studies of social
      determinants of mortality.
AB  - OBJECTIVE: To illustrate the potential sensitivity of ecological associations
      between mortality and certain socioeconomic factors to different methods of age
      adjustment. DATA SOURCES: Secondary analysis employing state-level data from
      several publicly available sources. Crude and age-adjusted mortality rates for
      1990 are obtained from the U.S. Centers for Disease Control. The Gini coefficient
      for family income and percent of persons below the federal poverty line are from
      the U.S. Bureau of Labor Statistics. Putnam's (2000) Social Capital Index was
      downloaded from http://www.bowlingalone.com; the Social Mistrust Index was
      calculated from responses to the General Social Survey, following the method
      described in Kawachi et al. (1997). All other covariates are obtained from the
      U.S. Census Bureau. STUDY DESIGN: We use least squares regression to estimate the
      effect of several state-level socioeconomic factors on mortality rates. We
      examine whether these statistical associations are sensitive to the use of
      alternative methods of accounting for the different age composition of state
      populations. Following several previous studies, we present results for the case
      when only mortality rates are age-adjusted. We contrast these results with those
      obtained from regressions of crude mortality on age variables. PRINCIPAL
      FINDINGS: Different age-adjustment methods can cause a change in the sign or
      statistical significance of the association between mortality and various
      socioeconomic factors. When age variables are included as regressors, we find no
      significant association between mortality and either income inequality, minority
      racial concentration, or social capital. CONCLUSIONS: Ecological associations
      between certain socioeconomic factors and mortality may be extremely sensitive to
      different age-adjustment methods.

PMID- 14727798
TI  - Nonlinearity in demographic and behavioral determinants of morbidity.
AB  - OBJECTIVE: To examine nonlinearity of determinants of morbidity in the United
      States DATA SOURCES: A secondary analysis of data on individuals with dietary
      data from the Cancer Epidemiology Supplement and National Health Interview Survey
      (NHIS) 1987, a cross-sectional, stratified random sample of the U.S. population
      (n = 22,080). STUDY DESIGN: A statistical exploration using additive multiple
      regression models. METHODS: A Morbidity Index (0-30 points), derived from 1987
      National Health Interview Survey data, combines number of conditions,
      hospitalizations, sick days, doctor visits, and degree of disability. Behavioral
      (health habits) variables were added to multivariate models containing
      demographic terms, with Morbidity Index and Self-assessed Health outcomes (n =
      17,612). Tables and graphs compare models of morbidity with self-assessed health
      models, with and without behavioral terms. Graphs illustrate curvilinear
      relationships. PRINCIPAL FINDINGS: Morbidity and health are associated
      nonlinearly with age, race, education, and income, as well as alcohol, diet
      change, vitamin supplement use, body mass index (BMI), marital status/living
      arrangement, and smoking. Diet change and supplement use, education, income,
      race/ethnicity, and age relate differently to self-assessed health status than to
      morbidity. Morbidity is strongly associated with income up to about dollars
      15,000 above poverty. Additional income predicts no further reduction in
      morbidity. Better health is strongly related to both higher income and education.
      After controlling for income, black race does not predict morbidity, but remains
      associated with lower self-assessed health. CONCLUSIONS: Good health habits, as
      captured in these models, are associated with a 10-20-year delay in onset and
      progression of morbidity.

PMID- 14727799
TI  - Socioeconomic gradients and low birth-weight: empirical and policy
      considerations.
AB  - OBJECTIVE: To examine whether socioeconomic status (SES) gradients emerge in
      health outcomes as early as birth and to examine the magnitude, potential
      sources, and explanations of any observed SES gradients. DATA SOURCES: The
      National Maternal and Infant Health Survey conducted in 1988. STUDY DESIGN: A
      multinomial logistic regression of trichotomized birth-weight categories was
      conducted for normal birth-weight (2,500-5,500 grams), low birth-weight (LBWT; <
      2,500 grams), and heavy birth-weight (> 5,500 grams). Key variables included
      income, education, occupational grade, state-level income inequality, and length
      of participation in Women-Infants-Children (WIC) for pregnant mothers. PRINCIPAL
      FINDINGS: A socioeconomic gradient for low birth-weight was discovered for an
      adjusted household income measure, net of all covariates in the unrestricted
      models. A gross effect of maternal education was explained by maternal smoking
      behaviors, while no effect of occupational grade was observed, net of household
      income. There were no significant state-level income inequality effects (Gini
      coefficient) for any of the models. In addition, participation in WIC was
      discovered to substantially flatten income gradients for short-term participants
      and virtually eliminate an income gradient among long-term participants.
      CONCLUSIONS: Although a materialist explanation for early-life SES gradients
      seems the most plausible (vis-a-vis psychosocial and occupational explanations),
      more research is needed to discover potential interventions. In addition, the
      notion of a monotonic gradient in which income is salutary across the full range
      of the distribution is challenged by these data such that income may cease to be
      beneficial after a given threshold. Finally, the success of WIC participation in
      flattening SES gradients argues for either: (a) the experimental efficacy of WIC,
      or (b) the biasing selection characteristics of WIC participants; either
      conclusion suggests that interventions or characteristics of participants
      deserves further study as a potential remedy for socioeconomic disparities in
      early-life health outcomes such as LBWT.

PMID- 14727800
TI  - Social determinants of tooth loss.
AB  - OBJECTIVES: To quantify racial and socioeconomic status (SES) disparities in oral
      health, as measured by tooth loss, and to determine the role of dental care use
      and other factors in explaining disparities. DATA SOURCES/STUDY SETTING: The
      Florida Dental Care Study, comprising African Americans (AAs) and non-Hispanic
      whites 45 years old or older who had at least one tooth. STUDY DESIGN: We used a
      prospective cohort design. Relevant population characteristics were grouped by
      predisposing, enabling, and need variables. The key outcome was tooth loss, a
      leading measure of a population's oral health, looked at before and after
      entering the dental care system. Tooth-specific data were used to increase
      inferential power by relating the loss of individual teeth to the disease level
      on those teeth. DATA COLLECTION METHODS: In-person interviews and clinical
      examinations were done at baseline, 24, and 48 months, with telephone interviews
      every 6 months. PRINCIPAL FINDINGS: African Americans and persons of lower SES
      reported more new dental symptoms, but were less likely to obtain dental care.
      When they did receive care, they were more likely to experience tooth loss and
      less likely to report that dentists had discussed alternative treatments with
      them. At the first stage of analysis, differences in disease severity and new
      symptoms explained tooth loss disparities. Racial and SES differences in
      attitudes toward tooth loss and dental care were not contributory. Because almost
      all tooth loss occurs by means of dental extraction, the total effects of race
      and SES on tooth loss were artificially minimized unless disparities in dental
      care use were taken into account. CONCLUSIONS: Race and SES are strong
      determinants of tooth loss. African Americans and lower SES persons had fewer
      teeth at baseline and still lost more teeth after baseline. Tooth-specific case
      mix adjustment appears, statistically, to explain social disparity variation in
      tooth loss. However, when social disparities in dental care use are taken into
      account, social disparities in tooth loss that are not directly due to clinical
      circumstance become evident. This is because AAs and lower SES persons are more
      likely to receive a dental extraction once they enter the dental care system,
      given the same disease extent and severity. This phenomenon underscores the
      importance of understanding how disparities in health care use, dental insurance
      coverage, and service receipt contribute to disparities in health. Absent such
      understanding, the total effects of race and SES on health can be underestimated.

PMID- 14727801
TI  - County-level income inequality and depression among older Americans.
AB  - OBJECTIVES: To examine (1) whether county-level income inequality is associated
      with depression among Americans aged 70 and older, taking into consideration
      county-level mean household income and individual-level socioeconomic status
      (SES), demographic characteristics, and physical health, and (2) whether income
      inequality effects are stronger among people with lower SES and physical health.
      DATA SOURCES: The individual-level data from the first wave of the Assets and
      Health Dynamics among the Oldest Old survey (1993-1994) were linked with the
      county-level income inequality and mean household income data from the 1990
      Census. STUDY DESIGN: Multilevel analysis was conducted to examine the
      association between income inequality (the Gini coefficient) and depression.
      PRINCIPAL FINDINGS: Income inequality was significantly associated with
      depression among older Americans. Those living in counties with higher income
      inequality were more depressed, independent of their demographic characteristics,
      SES, and physical health. The association was stronger among those with more
      illnesses. CONCLUSIONS: While previous empirical research on income inequality
      and physical health is equivocal, evidence for income inequality effects on
      mental health seems to be strong.

PMID- 14727802
TI  - Racial differences in the receipt of bowel surveillance following potentially
      curative colorectal cancer surgery.
AB  - OBJECTIVE: To investigate racial differences in posttreatment bowel surveillance
      after colorectal cancer surgery in a large population of Medicare patients. DATA
      SOURCES: We used a large population-based dataset: Surveillance, Epidemiology,
      and End Results (SEER) linked to Medicare data. STUDY DESIGN: This is a
      retrospective cohort study. We analyzed data from 44,768 non-Hispanic white,
      2,921 black, and 4,416 patients from other racial/ethnic groups, aged 65 and
      older at diagnosis, who had a diagnosis of local or regional colorectal cancer
      between 1986 and 1996, and were followed through December 31, 1998. Cox
      Proportional Hazards models were used to investigate the relation of race and
      receipt of posttreatment bowel surveillance. DATA COLLECTION: Sociodemographic,
      hospital, and clinical characteristics were collected at the time of diagnosis
      for all members of the cohort. Surgery and bowel surveillance with colonoscopy,
      sigmoidoscopy, and barium enema were obtained from Medicare claims using ICD-9-CM
      and CPT-4 codes. PRINCIPAL FINDINGS: The chance of surveillance within 18 months
      of surgery was 57 percent, 48 percent, and 45 percent for non-Hispanic whites,
      blacks, and others, respectively. After adjusting for sociodemographic, hospital,
      and clinical characteristics, blacks were 25 percent less likely than whites to
      receive surveillance if diagnosed between 1991 and 1996 (RR = 0.75, 95 percent CI
      = 0.70-0.81). CONCLUSIONS: Elderly blacks were less likely than non-Hispanic
      whites to receive posttreatment bowel surveillance and this result was not
      explained by measured racial differences in sociodemographic, hospital, and
      clinical characteristics. More research is needed to explore the influences of
      patient- and provider-level factors on racial differences in posttreatment bowel
      surveillance.

PMID- 14727803
TI  - Tackling health inequalities in the United Kingdom: the progress and pitfalls of
      policy.
AB  - GOAL: Assess the progress and pitfalls of current United Kingdom (U.K.) policies
      to reduce health inequalities. OBJECTIVES: (1) Describe the context enabling
      health inequalities to get onto the policy agenda in the United Kingdom. (2)
      Categorize and assess selected current U.K. policies that may affect health
      inequalities. (3) Apply the "policy windows" model to understand the issues faced
      in formulating and implementing such policies. (4) Examine the emerging policy
      challenges in the U.K. and elsewhere. DATA SOURCES: Official documents, secondary
      analyses, and interviews with policymakers. STUDY DESIGN: Qualitative, policy
      analysis. DATA COLLECTION: 2001-2002. The methods were divided into two stages.
      The first identified policies which were connected with individual inquiry
      recommendations. The second involved case-studies of three policies areas which
      were thought to be crucial in tackling health inequalities. Both stages involved
      interviews with policymakers and documentary analysis. PRINCIPAL FINDINGS: (1)
      The current U.K. government stated a commitment to reducing health inequalities.
      (2) The government has begun to implement policies that address the wider
      determinants. (3) Some progress is evident but many indicators remain stubborn.
      (4) Difficulties remain in terms of coordinating policies across government and
      measuring progress. (5) The "policy windows" model explains the limited extent of
      progress and highlights current and possible future pitfalls. (6) The U.K.'s
      experience has lessons for other governments involved in tackling health
      inequalities. CONCLUSIONS: Health inequalities are on the agenda of U.K.
      government policy and steps have been made to address them. There are some signs
      of progress but much remains to be done including overcoming some of the perverse
      incentives at the national level, improving joint working, ensuring appropriate
      measures of performance/progress, and improving monitoring arrangements. A
      conceptual policy model aids understanding and points to ways of sustaining and
      extending the recent progress and overcoming pitfalls.

PMID- 14727804
TI  - What new knowledge would help policymakers better balance investments for optimal
      health outcomes?
AB  - OBJECTIVE: Review the limitations in cross-sectoral health outcomes research and
      suggest a future research agenda. DATA SOURCES, STUDY DESIGN, DATA COLLECTION:
      Literature review and workshop discussion. PRINCIPAL FINDINGS: The research
      evidence that would aid public and private policy makers in answering the
      question the title poses is quite limited. CONCLUSIONS: Much more evidence from
      diverse disciplines is needed, and key areas are suggested. Criteria for progress
      by 2010 are proposed.

PMID- 14727805
TI  - Promises to keep (Part 1).

PMID- 14727806
TI  - Zoonoses of occupational health importance in contemporary laboratory animal
      research.
AB  - In contemporary laboratory animal facilities, workplace exposure to zoonotic
      pathogens, agents transmitted to humans from vertebrate animals or their tissues,
      is an occupational hazard. The primary (e.g., macaques, pigs, dogs, rabbits,
      mice, and rats) and secondary species (e.g., sheep, goats, cats, ferrets, and
      pigeons) of animals commonly used in biomedical research, as classified by the
      American College of Laboratory Animal Medicine, are established or potential
      hosts for a large number of zoonotic agents. Diseases included in this review are
      principally those wherein a risk to biomedical facility personnel has been
      documented by published reports of human cases in laboratory animal research
      settings, or under reasonably similar circumstances. Diseases are listed
      alphabetically, and each section includes information about clinical disease,
      transmission, occurrence, and prevention in animal reservoir species and humans.
      Our goal is to provide a resource for veterinarians, health-care professionals,
      technical staff, and administrators that will assist in the design and on-going
      evaluation of institutional occupational health and safety programs.

PMID- 14727807
TI  - Detection of early secretory antigenic target-6 antibody for diagnosis of
      tuberculosis in non-human primates.
AB  - Tuberculosis is one of the most economically devastating, zoonotic infections of
      captive non-human primates. The limitations of the tuberculin skin test, which is
      currently used to diagnose tuberculosis in living non-human primates, make it
      necessary to find new, simple, and economical diagnostic methods. We describe use
      of an enzyme-linked immunoassay to detect IgG antibodies against early secretory
      antigenic target (ESAT)-6, a small protein secreted by virulent tubercle bacilli,
      in paired (pre- and post-outbreak) sera from 57 non-human primates involved in an
      outbreak of Mycobacterium bovis infection in a research colony. Of 25 animals
      with tuberculosis lesions at necropsy, 22 (88%) had high serum levels of the ESAT
      6 antibody. The ESAT-6 antibody was found in 16% (5/32) of post-outbreak sera
      from animals in which tuberculosis could not be confirmed at necropsy. The strong
      association between the ESAT-6 antibody and tuberculosis in non-human primates
      documented in this study, together with the robustness of the serologic assay,
      make the ESAT-6 ELISA a valuable tool for diagnosis of tuberculosis in captive
      non-human primates.

PMID- 14727808
TI  - Dietary phytoestrogens accelerate the time of vaginal opening in immature CD-1
      mice.
AB  - The purpose of the study reported here was to determine the effects of dietary
      phytoestrogens on the time of vaginal opening (VO) in immature CD-1 mice, and to
      correlate it with phytoestrogen and total metabolizable energy (ME) contents of
      the diet in an effort to determine the most appropriate diets(s) for comparing or
      evaluating the estrogenic or antiestrogenic activity of endocrine disruptor
      compounds (EDC). Mice were weaned at postnatal day (PND) 15 and fed the test
      diets from PND 15 to 30. Vaginal opening was recorded from PND 20 to 30. The
      phytoestrogen content of the diet was highly predictive (P < 0.0001) of the
      proportion of mice with VO at PND 24. Total ME content also was significantly (P
      < 0.01) correlated with time of VO, although this variable was somewhat less
      predictive than was phytoestrogen content. Time of VO in mice was significantly
      (P < 0.05) accelerated in mice fed diets high in phytoestrogens, compared with
      those containing low phytoestrogen content. It was concluded that: dietary
      daidzein and genistein can significantly (P < 0.01) accelerate the time of VO in
      CD-1 mice; the advancement in time of VO is more highly correlated with daidzein
      and genistein contents of the diets than with total ME content; advancement in
      the time of VO is a sensitive end point for evaluating the estrogenic activity of
      EDCs, and should be part of the standard protocol for evaluating EDCs.
      Phytoestrogen-free diet(s) containing the same amount of ME should be used in
      bioassays that compare the time of VO, or increases in uterine weight as end
      points for evaluating the estrogenic activity of an EDC.

PMID- 14727809
TI  - Effect of animal bedding on rat liver endosome acidification.
AB  - Animal beddings, such as pine products, and environmental factors are known to
      induce liver drug-metabolizing cytochrome P450 enzymes. We observed that a change
      to pine-based rat bedding altered baseline and cAMP-stimulated rates of
      acidification in rat liver endosomes, apparently by decreasing ATP-dependent
      proton transport in the presence and absence of chloride. Although cAMP altered
      phosphorylation of protein kinase B and extracellular signal-regulated kinases 1
      and 2 (ERK 1,2) and p38 mitogen-activated protein kinases, changes in housing
      conditions did not affect baseline or cAMP-stimulated values of these or other
      selected signaling molecules. We conclude that compounds in rat bedding may alter
      not only drug metabolism, but also aspects of endocytosis.

PMID- 14727810
TI  - Mouse model of Sanfilippo syndrome type B: relation of phenotypic features to
      background strain.
AB  - Sanfilippo syndrome type B or mucopolysaccharidosis type III B (MPS IIIB) is a
      lysosomal storage disorder that is inherited in autosomal recessive manner. It is
      characterized by systemic heparan sulfate accumulation in lysosomes due to
      deficiency of the enzyme alpha-N-acetylglucosaminidase (Naglu). Devastating
      clinical abnormalities with severe central nervous system involvement and somatic
      disease lead to premature death. A mouse model of Sanfilippo syndrome type B was
      created by targeted disruption of the gene encoding Naglu, providing a powerful
      tool for understanding pathogenesis and developing novel therapeutic strategies.
      However, the JAX GEMM Strain B6.129S6-Naglutm1Efn mouse, although showing
      biochemical similarities to humans with Sanfilippo syndrome, exhibits aging and
      behavioral differences. We observed idiosyncrasies, such as skeletal dysmorphism,
      hydrocephalus, ocular abnormalities, organomegaly, growth retardation, and
      anomalies of the integument, in our breeding colony of Naglu mutant mice and
      determined that several of them were at least partially related to the background
      strain C57BL/6. These background strain abnormalities, therefore, potentially
      mimic or overlap signs of the induced syndrome in our mice. Our observations may
      prove useful in studies of Naglu mutant mice. The necessity for distinguishing
      background anomalies from signs of the modeled disease is apparent.

PMID- 14727811
TI  - Analysis of beta-catenin, Ki-ras, and microsatellite stability in azoxymethane
      induced colon tumors of BDIX/Orl Ico rats.
AB  - The aim of the study reported here was to investigate whether the azoxymethane
      (AOM)-induced colon cancer rat model mimics the human situation with regard to
      microsatellite stability, changes in expression of beta-catenin, and/or changes
      in the sequence of the proto-oncogene Ki-ras. Colon cancer was induced by
      administration of four weekly doses of AOM (15 mg/kg of body weight per week)
      separated by a one-week break between the second and third injections. As the
      histopathologic characteristics of this model resemble those of the human
      counterpart, further characterization of the genetic changes was undertaken. The
      animals were euthanized 28 to 29 weeks after the first AOM injection, and tumor
      specimens were taken for histologic and DNA analyses. Since microsatellite
      variation was found in only a few (< 2%) specimens, the model can be considered
      as having stable microsatellites. This result is in accordance with those of
      similar studies in other rat models and with most human colorectal cancers.
      Immunohistochemical analyses of beta-catenin did not reveal loss of gene
      activity, nor did the sequencing of Ki-ras reveal mutations. These results are in
      contrast to most findings in comparable rat studies. The deviations may be due to
      differences in exposure to the carcinogen or difference in strain and/or age. The
      lack of beta-catenin and Ki-ras alterations in this colon cancer model is unlike
      human sporadic colorectal cancers where these genetic changes are common
      findings.

PMID- 14727812
TI  - Cryopreservation of spermatozoa from closed colonies, and inbred, spontaneous
      mutant, and transgenic strains of rats.
AB  - We attempted to cryopreserve spermatozoa from closed colonies (Jcl:SD and
      Jcl:Wistar), and inbred (BN/Crj, F3441 DuCrj, LEW/Crj, Long-Evans and WKY/NCrj),
      mutant (Zitter [WTC.ZI-zi] and Tremor [TRM]), transgenic (human A-transferase
      [A], and green fluorescent protein [GFP]) strains of rats. Rat epididymal
      spermatozoa suspended in cryopreservation solution (23% egg yolk, 8% lactose
      monohydrate, and 0.7% Equex Stm, pH 7.4, adjusted with 10% Tris [hydroxymethy]
      aminomethane) were frozen and stored at -196 degrees C. After thawing at 37
      degrees C, the spermatozoa were instilled into the tip of each uterine horn of
      the recipients. A total of five recipient females for each strain were
      inseminated with cryopreserved spermatozoa, and normal live offspring of all
      strains (Jcl:SD: 11, Jcl:Wistar: 13, BN/Crj: 9, F344/DuCrj: 28, LEW/Crj: 4, Long
      Evans: 6, WKY/NCrj: 8, TRM: 24, WTC.ZI-zi: 27, A: 30 and GFP: 20) were obtained.

PMID- 14727813
TI  - Fine mapping of the circling (cir) gene on the distal portion of mouse chromosome
      9.
AB  - Circling mice manifest profound deafness, head-tossing, and bi-directional
      circling behavior, which they inherit in autosomal recessive manner. Histologic
      examination of the inner ear reveals abnormalities of the region around the organ
      of Corti, spiral ganglion neurons, and outer hair cells. A genetic linkage map
      was constructed for an intraspecific backcross between cir and C57BL/6J mice. The
      cir gene was mapped to a region between D9Mit116/D9Mit15 and D9Mit38 on mouse
      chromosome (Chr) 9. Estimated distances between cir and D9Mit116, and between cir
      and D9Mit38 were 0.70 +/- 0.40 and 0.23 +/- 0.23 cM, respectively. Order of the
      markers was defined as follows: centromere - D9Mit182 - D9Mit51/D9Mit79/D9Mit310 
      D9Mit212/D184 - D9Mit116/D9Mit15 - cir - D9Mit38 - D9Mit20 - D9Mit243 - D9Mit16 
      D9Mit55/D9Mit125 - D9Mit281. On the basis of genetic mapping, we constructed a
      yeast artificial chromosome (YAC) contig across the cir region. The cir gene is
      located between the lactotransferrin (ltf) and microtubule-associated protein
      (map4) genes. The distal portion of mouse Chr 9 encompassing the cir region is
      homologous with human chromosome 3p21, which contains the Deafness, form B:
      Autosomal Recessive Deafness (DFNB6) locus. Therefore, the circling mouse is a
      potential animal model for DFNB6 deafness in humans.

PMID- 14727814
TI  - Magnetic resonance imaging and immunoblot analyses in rats with experimentally
      induced cerebral alveolar echinococcosis.
AB  - The early stage of experimentally induced secondary cerebral alveolar
      echinococcosis (AE) in rats was investigated by use of magnetic resonance imaging
      (MRI) and immunoblot (western blot) analyses. Thirty-six female Wistar rats (6 to
      8 weeks old) were injected intracranially with a 10% homogenate of echinococcal
      larval tissues in which the concentrations of microvesicles and protoscolices
      were estimated to be 3.8 and 1.5 x 10(4)/ml, respectively. To observe the fine
      structure of the rat brain, MRI was performed under a high magnetic field of 7.05
      T. Histologic examination also was performed. The T2-weighted MR images revealed
      a hyperintense region in the cerebral cortex at two weeks after injection of the
      homogenate. At three weeks after injection, this region was found to have cysts
      on the basis of results of histologic examination. Signal-void regions
      corresponding to hyperplasia and the subsequent calcification of the cuticle
      layer at six and 13 weeks after injection, respectively, were observed in T2
      weighted and proton density MR images. On the other hand, at nine weeks after
      injection, AE was discernible by use of western blot analysis of sera with
      antibodies of two epitopes (Em18 and Em16) of E. multilocularis. Using this
      secondary cerebral AE animal model, it was concluded that the MRI method was
      suitable for early detection of secondary cerebral AE.

PMID- 14727815
TI  - Studies of heart disease and failure in aged female squirrel monkeys (Saimiri
      sp.).
AB  - Lesions consistent with heart failure were found in 23 of 88 adult squirrel
      monkeys that died between 1995 and 1999 at the Squirrel Monkey Breeding and
      Research Resource (SMBRR). This provided a rationale for a study surveying aged
      animals in the SMBRR for normal cardiac characteristics, using echocardiography
      (ECHO) and electro-cardiogram. In the pilot study, ECHO and electrocardiography
      were performed on 59 healthy female squirrel monkeys aged 10 years or older and
      39 five-year-old monkeys. Parameters were heart rate, P-wave duration and
      amplitude, and PR, QRS, and QT intervals (electrocardiography), and ejection
      fraction. Two animals with cardiomyopathy were identified and received similar
      testing. Advanced-study animals had the same measurements, plus left ventricular
      internal diameter-systole (LVIDs) and -diastole (LVIDd), left atrial diameter
      diastole (LADd) and aortic root diameter-diastole (AoRDd) by use of ECHO.
      Significant differences were found between groups in LADd, and P-wave and QRS
      interval durations. In a clinical context, these differences were not considered
      to be substantial. Normal aged female squirrel monkeys had significant increases
      in heart dimension and longer P- and QRS-wave durations than did monkeys of a
      five-year-old control group, although the increases were not considered
      clinically relevant. This study documents myocardial dynamics in healthy saimiri
      and those with cardiomyopathy.

PMID- 14727816
TI  - Clinical and microbiologic characterization of hemorrhagic pneumonia due to
      extraintestinal pathogenic Escherichia coli in four young dogs.
AB  - Over a 21-month period, three Beagle dogs and one mixed-breed dog at our facility
      developed fatal pneumonia. The four dogs, all purpose bred, came from three
      vendors and had received the standard canine vaccines prior to shipment. In each
      instance, the affected dog had been shipped to our facility within the past 10
      days. Three cases presented as a peracute clinical syndrome, and all had gross
      and microscopic findings consistent with hemorrhagic pneumonia. Escherichia coli
      was isolated from the lungs of all four dogs. Results of testing of lung tissue
      for canine parainfluenza virus and canine adenovirus were negative. Escherichia
      coli was also isolated from blood of three of the four dogs. Serotyping of the E.
      coli isolates indicated that two were serotype 06 and two were 04. Isolates from
      all four dogs were positive for the virulence factors alpha hemolysin and
      cytotoxic necrotizing factor 1 and for the adhesin factor class-III papG allele.
      These traits place the isolates in the class of extraintestinal pathogenic E.
      coli, which is being increasingly implicated as a cause of extraintestinal
      infections in animals and humans and may represent a zoonotic risk to humans
      working with research dogs.

PMID- 14727817
TI  - Causes of benign asymptomatic pneumoperitoneum.

PMID- 14727818
TI  - Redefining appropriate use of antibiotics.

PMID- 14727819
TI  - Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

PMID- 14727820
TI  - Hepatitis B.
AB  - Hepatitis B causes significant morbidity and mortality worldwide. More than 400
      million persons, including 1.25 million Americans, have chronic hepatitis B. In
      the United States, chronic hepatitis B virus infection is responsible for about
      5,000 annual deaths from cirrhosis and hepatocellular carcinoma. Hepatitis B
      virus is found in body fluids and secretions; in developed countries, the virus
      is most commonly transmitted sexually or via intravenous drug use. Occupational
      exposure and perinatal transmission do occur but are rare in the United States.
      Effective vaccines for hepatitis B virus have been available since 1982; infant
      and childhood vaccination programs introduced in the 1990s have resulted in a
      marked decrease in new infections. Risk factors for progression to chronic
      infection include age at the time of infection and impaired immunity. From 15 to
      30 percent of patients with acute hepatitis B infection progress to chronic
      infection. Medical therapies for chronic hepatitis B include interferon alfa-2b,
      lamivudine, and the nucleotide analog adefovir dipivoxil.

PMID- 14727821
TI  - Information from your family doctor. Hepatitis B infection.

PMID- 14727822
TI  - Pityriasis rosea.
AB  - Pityriasis rosea is a common, acute exanthem of uncertain etiology. Viral and
      bacterial causes have been sought, but convincing answers have not yet been
      found. Pityriasis rosea typically affects children and young adults. It is
      characterized by an initial herald patch, followed by the development of a
      diffuse papulosquamous rash. The herald patch often is misdiagnosed as eczema.
      Pityriasis rosea is difficult to identify until the appearance of characteristic
      smaller secondary lesions that follow Langer's lines (cleavage lines). Several
      medications can cause a rash similar to pityriasis rosea, and several diseases,
      including secondary syphilis, are included in the differential diagnosis. One
      small controlled trial reported faster clearing of the exanthem with the use of
      erythromycin, but the mechanism of effect is unknown. Resolution of the rash may
      be hastened by ultraviolet light therapy but not without the risk of
      hyperpigmentation. Topical or systemic steroids and antihistamines often are used
      to relieve itching.

PMID- 14727823
TI  - Information from your family doctor. Pityriasis rosea.

PMID- 14727825
TI  - Information from your family doctor. Birth control using a diaphragm.

PMID- 14727824
TI  - Diaphragm fitting.
AB  - When used with a spermicide, the diaphragm can be a more effective barrier
      contraceptive than the male condom. The diaphragm allows female-controlled
      contraception. It also provides moderate protection against sexually transmitted
      diseases and is less expensive than some contraceptive methods (e.g., oral
      contraceptive pills). However, diaphragm use is associated with more frequent
      urinary tract infections. Contraindications to use of a diaphragm include known
      hypersensitivity to latex (unless the wide seal rim diaphragm is used) or a
      history of toxic shock syndrome. A diaphragm is fitted properly if the posterior
      rim rests comfortably in the posterior fornix, the anterior rim rests snugly
      behind the pubic bone, and the cervix can be felt through the dome of the device.
      The diaphragm should not be left in the vagina for longer than 24 hours. When the
      diaphragm is the chosen method of contraception, patient education is key to
      compliance and effectiveness. An extended visit with the physician or a nurse may
      be required for a woman to learn proper insertion, removal, and care of the
      diaphragm.

PMID- 14727826
TI  - Information from your family doctor. Using your diaphragm.

PMID- 14727827
TI  - Vertebral compression fractures in the elderly.
AB  - Compression fracture of the vertebral body is common, especially in older adults.
      Vertebral compression fractures usually are caused by osteoporosis, and range
      from mild to severe. More severe fractures can cause significant pain, leading to
      inability to perform activities of daily living, and life-threatening decline in
      the elderly patient who already has decreased reserves. While the diagnosis can
      be suspected from history and physical examination, plain roentgenography, as
      well as occasional computed tomography or magnetic resonance imaging, are often
      helpful in accurate diagnosis and prognosis. Traditional conservative treatment
      includes bed rest, pain control, and physical therapy. Interventional procedures
      such as vertebroplasty can be considered in those patients who do not respond to
      initial treatment. Family physicians can help patients prevent compression
      fractures by diagnosing and treating predisposing factors, identifying high-risk
      patients, and educating patients and the public about measures to prevent falls.

PMID- 14727828
TI  - Diagnostic approach to tinnitus.
AB  - Tinnitus is a common disorder with many possible causes. Most cases of tinnitus
      are subjective, but occasionally the tinnitus can be heard by an examiner.
      Otologic problems, especially hearing loss, are the most common causes of
      subjective tinnitus. Common causes of conductive hearing loss include external
      ear infection, cerumen impaction, and middle ear effusion. Sensorineural hearing
      loss may be caused by exposure to excessive loud noise, presbycusis, ototoxic
      medications, or Meniere's disease. Unilateral hearing loss plus tinnitus should
      increase suspicion for acoustic neuroma. Subjective tinnitus also may be caused
      by neurologic, metabolic, or psychogenic disorders. Objective tinnitus usually is
      caused by vascular abnormalities of the carotid artery or jugular venous systems.
      Initial evaluation of tinnitus should include a thorough history, head and neck
      examination, and audiometric testing to identify an underlying etiology.
      Unilateral or pulsatile tinnitus may be caused by more serious pathology and
      typically merits specialized audiometric testing and radiologic studies. In
      patients who are discomforted by tinnitus and have no remediable cause, auditory
      masking may provide some relief.

PMID- 14727829
TI  - Information from your family doctor. Tinnitus.

PMID- 14727830
TI  - Thromboembolism.

PMID- 14727831
TI  - Screening for osteoporosis in postmenopausal women.

PMID- 14727832
TI  - Cutaneous manifestation of a systemic disease.

PMID- 14727833
TI  - Information from your family doctor. Painful urination.

PMID- 14727834
TI  - Information from your family doctor. Urinary reflux.

PMID- 14727835
TI  - Information from your family doctor. Urinary tract infections in children.

PMID- 14727836
TI  - Information from your family doctor. Urinary tract infections during pregnancy.

PMID- 14727837
TI  - Information from your family doctor. Urinary tract infections in adults.

PMID- 14727838
TI  - Recommended Childhood and Adolescent Immunization Schedule, United States,
      January to June, 2004 and update on childhood immunizations.

PMID- 14727839
TI  - Should doctors call in sick?

PMID- 14727840
TI  - Kinetics of pramlintide degradation in aqueous solution as a function of
      temperature and pH.
AB  - The stability of the 37-amino acid peptide pramlintide, in aqueous solution, was
      studied as a function of pH and temperature. Samples of pramlintide formulated as
      a parenteral product were exposed to elevated temperatures and to realistic
      storage conditions for as long as 30 months. Pramlintide degradation was
      monitored by three high-performance liquid chromatography (HPLC) methods: a
      reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method for
      percentage purity determination by area normalization, plus a second RP-HPLC
      method for potency determination versus external standards. The pH-rate profile
      for pramlintide shows increasing degradation rate constants with increasing pH
      over the range pH = 3.5 to 5.0. The Arrhenius expression for pramlintide
      degradation at pH = 4.0 over the temperature range 5 degrees C to 50 degrees C is
      ln(k(0))= 37.39-21.900/RT, where k(0) is the zero-order rate constant (in %/mo)
      for pramlintide degradation. The pramlintide parenteral product formulated at pH
      = 4.0 is extremely stable, with percentage purity and percentage potency loss of
      only approximately 2% over 30 months at 5 degrees C. The formulated pramlintide
      drug product has acceptable shelf life for long-term storage at 5 degrees C and
      up to a 30-day patient use when stored at ambient temperature.

PMID- 14727841
TI  - Pramlintide injection drug product robustness studies.
AB  - The article examines the effects of temperature excursions and actual dose
      withdrawal on the quality of pramlintide injection, a multidose liquid parenteral
      formulation. Studies were designed to demonstrate product robustness under
      conditions that may occur during patient use. Pramlintide %Purity was determined
      by two high-performance liquid chromatography (HPLC) methods, a reversed-phase
      (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method. A second RP-HPLC method
      was used to determine pramlintide potency and the concentration of the m-cresol
      preservative. Antimicrobial preservative effectiveness testing was per USP and
      European Pharmacopeia (Ph. Eur.). Short-term stability studies were undertaken to
      probe the effects of the following conditions: 5 degrees C to 40 degrees C and 5
      degrees C to -20 degrees C temperature cycling over 10 days; once daily or four
      times daily dose withdrawal over 12 or 42 days; and combined 30 degrees C storage
      and four-times daily dose withdrawal over 42 days. In all cases, pramlintide
      %Purity and potency values remained essentially unchanged or unchanged relative
      to controls. Similarly, product appearance, and m-cresol concentration and
      preservative effectiveness were not significantly affected by the stress
      conditions used in the 5 studies. Pramlintide injection drug product is extremely
      robust to challenging stress conditions that may occur during patient use of this
      multidose product for chronic administration.

PMID- 14727842
TI  - Influence of formulation and process parameters on pellet production by powder
      layering technique.
AB  - The goal of the present study was to evaluate the influence of the formulation
      and operating conditions on pellet preparation by pan technique. To this end, a
      new pelletization process, typified by the application of powdered drug on sugar
      based cores using the GS coating system was studied. Inert cores were
      intermittently treated with micronized drug powder and adhesive solution. This
      treatment led to the formation of multiple layers of drug particles around an
      inert core resulting in the production of pellets that can further be coated by
      different polymers to obtain modified release formulations. Different procedures
      have been used to evaluate a series of important parameters such as initial core
      weight; speed of powder application; speed, type, and position of the atomizers;
      atomization degree; temperature; and air cap. Good yield of drug layering was
      obtained by adjusting the quantity of both the drug powder to apply and the
      binder solution. Pellets obtained following the optimal operating conditions
      (defined in a pre-formulation study) were film coated with the acrylic polymer
      Eudragit L30D in order to produce a model formulation consisting of enteric
      polymer-coated pellets containing ibuprofen. During its preparation, the
      formulation showed no degradation of the drug; moreover, a low percentage of
      residual humidity was obtained, indicating that this system is very efficient for
      the production of highly stable formulations. This study showed the good
      performance of the GS automated pan-coating system in obtaining enteric coated
      pellets prepared by powder layering technique using aqueous solutions.

PMID- 14727843
TI  - Next generation fluidized bed granulator automation.
AB  - A system for fluidized bed granulator automation with in-line multichannel near
      infrared (NIR) moisture measurement and a unique air flow rate measurement design
      was assembled, and the information gained was investigated. The multivariate
      process data collected was analyzed using principal component analysis (PCA). The
      test materials (theophylline and microcrystalline cellulose) were granulated and
      the calibration behavior of the multichannel NIR set-up was evaluated against
      full Fourier Transform (FT) NIR spectra. Accurate and reliable process air flow
      rate measurement proved critical in controlling the granulation process. The
      process data describing the state of the process was projected in two dimensions,
      and the information from various trend charts was outlined simultaneously. The
      absorbence of test material at correction wavelengths (NIR region) and the nature
      of material-water interactions affected the detected in-line NIR water signal.
      This resulted in different calibration models for the test materials. Development
      of process analytical methods together with new data visualization algorithms
      creates new tools for in-process control of the fluidized bed granulation.

PMID- 14727844
TI  - Quantitative analysis of thymosin alpha1 in human serum by LC-MS/MS.
AB  - A high performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)
      method was developed to measure the thymosin alpha 1 (Talpha1) concentration in
      human serum. Ta1 in human serum was determined by solid phase extraction and
      reverse phase LC-MS/MS. The high-performance liquid chromatography (HPLC) system
      interfaced with the MS/MS system with a Turbo Ion spray interface. Positive ion
      detection and multiple reaction monitoring (MRM) mode were used for this human
      serum quantitation. Eight different concentration standards were used to
      establish the detection range. Six quality control (QC) and 2 matrix blanks were
      checked by calibration curves performed on the same day. The lower quantitation
      limit was 0.5 ng/mL Talpha1 in human serum. Calibration curves were established
      between 0.5 to 100 ng/mL by weighted linear regression. The correlation
      coefficients for different days were 0.9955 or greater. Quantitation of Talpha1
      by the LC-MS/MS method is fast, accurate, and precise.

PMID- 14727845
TI  - Circular dichroism simulation shows a site-II-to-site-I displacement of human
      serum albumin-bound diclofenac by ibuprofen.
AB  - PURPOSE: The purpose of this study was to confirm the hypothesis that a site-II
      to-site-I displacement takes place when some nonsteroidal anti-inflammatory drugs
      are displaced by another drug from their high-affinity binding site to a site of
      lower affinity on human serum albumin (HSA). METHODS: Diclofenac, sodium salt,
      was used as a representative example because of its prominent reversal of the
      Cotton effect. Effects of site-specific drugs on the free fraction of diclofenac
      were determined by equilibrium dialysis, and effects on induced circular
      dichroism (CD) of diclofenac bound to HSA were studied by CD and CD simulation
      techniques. RESULTS: Ibuprofen, a site-II-specific drug, altered the CD spectrum
      of the diclofenac-HSA complex at a molar ratio of 0.5 : 1 to that obtained at a
      higher ratio (5:1) without ibuprofen. The induced CD spectrum obtained in the
      presence of ibuprofen was very similar to one that assumed that all diclofenac
      displaced from its high-affinity binding site (site II) became rebound to a lower
      affinity site (site I). The rebinding could be influenced by a free energy
      linkage between the two sites which would make site I (or parts thereof) more
      suitable for diclofenac binding. CONCLUSION: We have confirmed the existence of a
      site II-to-site I displacement, which is very striking and pharmacologically
      important, because the concentration of unbound drug being displaced is much
      lower than expected for a competitive mechanism.

PMID- 14727846
TI  - Effect of gramicidin on percutaneous permeation of a model drug.
AB  - This study investigated the enhancement effect of gramicidin, a cationic
      ionophore, on percutaneous absorption of a model drug, benzoic acid (BA), through
      rat abdominal skin. The mechanisms by which gramicidin increased skin
      permeability to BA were also investigated. Degree of hydration measured by the
      Karl Fisher method, the concentration gradient measured by cryostat analysis, and
      lipid concentration measured by the Fiske-Subbarow method were evaluated and
      compared. The results showed that BA permeation profiles through rat abdominal
      skin followed dose- and volume-dependent patterns. The pretreatment of gramicidin
      increased the permeation rate of BA through rat abdominal skin compared with the
      untreated control (18.89 vs. 10.86 microg/cm2/hour). Change in skin permeation
      rate of BA after gramicidin pretreatment was closely correlated with the
      remaining skin water content. There were no significant differences in the
      amounts of phospholipid phosphorous between gramicidin pretreated and untreated
      skin. The enhancing effect of gramicidin on percutaneous absorption of a model
      drug is mainly attributed to increasing the diffusivity in the hydration domain
      of the skin and rearranging the lipid bilayer in the stratum corneum.

PMID- 14727847
TI  - Scale-up effects on dissolution and bioavailability of propranolol hydrochloride
      and metoprolol tartrate tablet formulations.
AB  - This study evaluated the effects of batch size on the in vitro dissolution and
      the in vivo bioavailability of immediate release formulations of propranolol
      hydrochloride and metoprolol tartrate. The formulations were manufactured as
      small and large batches (6 kg and 60 kg for propranolol; 14 kg and 66 kg for
      metoprolol), and dissolution was performed using USP Apparatus I at 100 rpm and
      pH 1.2. Two panels of 14 subjects each were randomly assigned to receive the
      small and large batches of either propranolol or metoprolol in an open,
      randomized single-dose study. Blood samples were collected over a 24-hour
      (propranolol) or 18-hour (metoprolol) period and analyzed by validated methods.
      As determined by the f2 metric (similarity factor), the dissolution of the small
      and large batches of propranolol and metoprolol was similar. The mean Cmax and
      AUC(inf) for the small batch of propranolol were 79.0 microg/L and 536
      microg/L/hr, and for the large batch they were 83.5 microg/L and 575 microg/L/hr.
      Cmax and AUC(inf) for the small batch of metoprolol were found to be 95.5
      microg/L and 507 microg/L/hr and for the large batch, 95.1 microg/L and 495
      microg/L/hr. The 90% confidence intervals for the small and large batches were
      within the 80% to 120% range for lnCmax, and lnAUC(inf) for both the propranolol
      and metoprolol formulations. These results suggest that the scale-up process does
      not significantly affect the bioavailability of highly soluble, highly permeable
      drugs and in vitro dissolution tests may be useful in predicting in vivo
      behavior.

PMID- 14727848
TI  - Factorial analysis of the influence of dissolution medium on drug release from
      carrageenan-diltiazem complexes.
AB  - This research studied the influence of buffer composition, pH, and ionic strength
      on the release of diltiazem hydrochloride from a complex of the drug with lambda
      carrageenan. Two viscosity grades of carrageenan were also compared. A factorial
      analysis was used to evaluate the influence of individual variables and their
      interactions. Both the complex solubility, measured as the drug concentration in
      equilibrium with the solid complex, and the drug release rate from constant
      surface area were considered. The increase of ionic strength significantly
      increased complex solubility in all the buffer systems. A significant effect of
      polymer grade on complex solubility was evidenced only in phosphate buffer with a
      pH of 6.8, indicating lower solubility of the complex when higher polymer
      molecular weight was involved. In most cases, drug release rate decreased when
      high polymer grade was involved in the complex. Ionic strength did not always
      have a significant effect on drug release rate and was quantitatively less
      important than for solubility. Ionic strength especially affected the drug
      release profiles. At higher ionic strength drug release was no longer constant,
      but decreased with time, probably because of lower polymer solubility.

PMID- 14727849
TI  - Effect of several factors on the mechanical properties of pressure-sensitive
      adhesives used in transdermal therapeutic systems.
AB  - The effects of coating thickness, type of adhesive, and type and concentration of
      enhancer on the mechanical properties of two acrylic pressure-sensitive adhesives
      (PSAs) were investigated using a 2(4) factorial design and an optimization
      technique. Sixteen formulations containing 0% or 10% of either caprylic acid or
      methyl laurate in two different PSAs, namely Duro-Tak 87-2196 and Duro-Tak 87
      2097, were prepared. The adhesive properties of these laminates were evaluated by
      applying the 90 degrees Dynamic Adhesive Strength Peel Test (90 degrees DASPT)
      and 1800 Release Liner Peel Test (180 degrees RLPT). Coating thickness,
      concentration of enhancer, and type of adhesive did affect the 90 degrees DASPT.
      For the 180 degrees RLPT, the most significant factors were coating thickness and
      concentration of enhancer, with a strong interaction observed between the two.
      Coating thickness and concentration of enhancer were also used to create
      mathematical models that correlated these factors with the mechanical properties
      of the PSAs. For this purpose, the optimization technique 3(2) was applied. It
      was found that the correlation of the above factors can be adequately described
      with polynomial equations, which can be used for predicting the mechanical
      properties of the laminates containing the above PSAs and methyl laurate (0%
      10%).

PMID- 14727850
TI  - Sustained activity and release of leuprolide acetate from an in situ forming
      polymeric implant.
AB  - The primary objective of this study was to evaluate the effect of drug loading on
      the release of leuprolide acetate from an injectable polymeric implant, formed in
      situ, and efficacy of the released drug in suppressing serum testosterone levels
      in dogs for at least 90 days. An additional objective was to compare the optimum
      implant formulation with a commercial microsphere product. Evaluated implant
      formulations contained 45% w/w 75/25 poly (DL-lactide-co-glycolide) polymer
      having an intrinsic viscosity of 0.20 dL/g, dissolved in N-methyl-2-pyrrolidone.
      Irradiated polymer solution was mixed with leuprolide at different drug loads
      (3%, 4.5%, and 6% w/w) prior to subcutaneous administration to dogs. Dog serum
      was analyzed for testosterone (RIA) and leuprolide (LC/MS/MS) levels and
      comparisons within the three implant formulation groups were made. Varying the
      drug load did not significantly affect the release of leuprolide or efficacy of
      the implant formulation. Thus, the 6% w/w formulation with the smaller injection
      volume was selected for comparison with the commercial LUPRON Depot product,
      which was administered intramuscularly at a similar dosage. These comparisons of
      serum testosterone and leuprolide levels showed no significant difference in the
      pharmacologic efficacy even though drug levels were different at a number of
      points. This was mainly due to associated high standard deviations. Based on
      these studies, the 6% w/w leuprolide implant formulation was considered to be a
      suitable candidate for further development. Additional benefits of this system
      include its simple manufacturing and lower costs.

PMID- 14727851
TI  - Liposome-based formulations for the antibiotic nonapeptide Leucinostatin A:
      Fourier transform infrared spectroscopy characterization and in vivo toxicologic
      study.
AB  - Leucinostatin-A is a nonapeptide isolated from Paecilomyces marquandii,
      Paecilomyces lilacinus A257, and Acremonium sp., exerting remarkable phytotoxic,
      antibacterial (especially against Gram-positive) and antimycotic activities. With
      the aim to find alternative formulation for in vivo administration, a number of
      Leucinostatin-A-loaded liposomal formulations have been prepared and
      characterized. Both large unilamellar vesicles and multilamellar vesicles
      consisting of synthetic and natural lipids were evaluated. In addition, to
      determine the nature of peptide-membrane interactions and the stability of
      liposomes loaded with Leucinostatin-A, a Fourier Transform Infrared Spectroscopy
      study was performed. The results suggest that the mode of interaction of the
      peptide is dependent on its concentration, on bilayer fluidity, and on liposome
      type. Finally, the LD50 of both free and liposome-delivered Leucinostatin-A was
      determined in mice. These results suggest that the incorporation of Leucinostatin
      A into liposomes may result in decreased Leucinostatin-A toxicity, as the
      intraperitoneal administration of Leucinostatin-A-loaded liposomes reduced the
      LD50 of Leucinostatin-A 15-fold.

PMID- 14727852
TI  - The stabilization and release of hirudin from liposomes or lipid-assemblies
      coated with hydrophobically modified dextran.
AB  - Hirudin is a 65-amino acid peptide and the most potent and specific known
      inhibitor of thrombin (K(i) = 0.2 pM). The short elimination half-life of hirudin
      from the body (1 hour) necessitates the use of a sustained and controlled
      delivery system. A proliposome method was used to entrap hirudin in liposomes
      coated with palmitoyl dextran-coated liposomes and lipid-assemblies. In vitro
      release studies of hirudin were performed using the lipid systems enclosed in
      dialysis membranes or deposited in the pores of a vascular graft. The activity of
      hirudin and released hirudin was measured using a thrombin chromogenic substrate
      assay. Entrapment efficiencies of hirudin in lipid-assemblies approached 100%,
      however, the release of hirudin from these systems was rapid with 90% released in
      17 hours. Entrapment efficiencies of hirudin in coated-liposomes ranged from 5%
      to 55% and were dependent on several variables. Palmitoyl dextran- coated
      liposomes showed a burst of 30% hirudin released in 5 hours with an additional
      10% to 35% released over the next 600 hours. In all samples, 30-40% of the
      hirudin remained associated with the lipid-systems even after 600 hours. The
      released hirudin retained only 33% of its ability to inhibit thrombin when
      released from uncoated liposomes. However, hirudin retained 95% of its thrombin
      inhibitory activity when released from palmitoyl dextran-coated liposomes. Coated
      liposomes were found to stabilize hirudin and result in greater retention of
      hirudin's ability to inhibit thrombin's enzymatic activity, although the
      mechanism is not yet understood.

PMID- 14727853
TI  - A novel in vitro release technique for peptide containing biodegradable
      microspheres.
AB  - The purpose of this study was to develop and evaluate a dialysis in vitro release
      technique for peptide-containing poly(d, l-lactide-co-glycolide) (PLGA)
      microspheres (ms) that would correlate with in vivo data. Using a luteinizing
      hormone- releasing hormone analogue (LHRH), Orntide acetate, solubility and
      stability were determined in 0.1 M phosphate buffer (PB), pH 7.4, and in 0.1 M
      acetate buffer (AB), pH 4.0, with high-performance liquid chromotography (HPLC),
      and peptide permeability through a dialysis membrane (molecular weight cut-off
      300,000) was determined. Orntide ms were prepared by a dispersion/solvent
      extraction/evaporation method and characterized for drug content (HPLC), particle
      size distribution (laser diffraction method), and surface morphology (scanning
      electron microscopy). In vitro release was studied in PB using a conventional
      extraction method and with a new dialysis method in AB. Gravimetric analyses of
      polymer mass loss and matrix hydration, and peptide adsorption to blank PLGA ms
      (50:50, M(w) 28 022) were carried out in PB and AB upon incubation at 37 degrees
      C. Serum Orntide and testosterone levels in rats after administration of Orntide
      ms were determined by radioimmunoassay. Orntide acetate solubility was influenced
      by pH; approximately 2.3 mg/mL dissolved in PB and > 18 mg/mL in AB. Stability
      was pH- and temperature-dependent. The peptide was very stable at pH 4.0, 4
      degrees C, but degraded rapidly at pH 7.4, 37 degrees C. Peptide permeability
      through the dialysis membrane was accelerated by agitation and >95% equilibrium
      was reached within 48 hours. The overall release rate was higher with the
      dialysis method. Mass loss of the Orntide ms was faster in AB (50% loss in 3
      weeks; 95% in 35 days) than in PB (65% in 35 days). In contrast, hydration after
      35 days was 4-fold higher in PB. The nonspecific adsorption to blank ms was
      greater in PB (128 microg Orntide/10 mg PLGA) compared with AB (< 5 microg
      Orntide/ 10 mg PLGA). Administration of 30-day Orntide PLGA ms to rats resulted
      in an initial serum Orntide level of 21 ng/mL after 6 hours and a Cmax of 87
      ng/mL after 6 days. Testosterone levels were suppressed immediately after ms
      administration (3 mg Orntide /Kg) from 5.2 ng/mL to 0.3 ng/mL (after 24 hours)
      and remained suppressed for 38 days. Orntide acetate solubility and degradation
      kinetics were markedly influenced by pH of the buffer systems and mass loss;
      matrix hydration, as well as the nonspecific adsorption to blank ms, was pH
      dependent. The in vitro release profile obtained with the dialysis method in AB
      correlated well with the in vivo data, thereby providing a more reliable
      prediction of in vivo performance.

PMID- 14727854
TI  - Dynamic changes in size distribution of emulsion droplets during ethyl acetate
      based microencapsulation process.
AB  - This study investigated the dynamic effect of the emulsification process on
      emulsion droplet size in manufacturing microspheres using ethyl acetate as an
      organic solvent. A dispersed phase consisting of poly(lactide-co-glycolide) and
      ethyl acetate was emulsified in a poly(vinyl alcohol) aqueous solution for a
      predetermined time ranging from 2 to 9, 16, 23, 30, 40, 50, or 60 minutes. Ethyl
      acetate was then quickly extracted to transform emulsion droplets into solidified
      microspheres, and their size distribution was determined. This experimental
      design allowed quantification of the size distribution of emulsion droplets over
      the course of emulsification. When emulsification time was extended from 2 to 60
      minutes, the emulsion droplets decreased in size from 98.1 to 50.3 microm and
      their surface area increased from 0.07 to 0.29 m2/g. Overall, prolonging
      emulsification time up to 60 minutes resulted in the progressive evolution of
      smaller emulsion droplets (1-60 microm) and the simultaneous disappearance of
      larger ones (> 81 microm). Increases in the total number of microspheres and
      their surface area were caused mainly by continuous fragmentation of emulsion
      droplets before ethyl acetate extraction. The increase in the smaller microsphere
      population might also be due in part to shrinkage of microspheres. These results
      show that the onset of ethyl acetate extraction influenced the kinetics of the
      breakup and formation of emulsion droplets, thereby affecting to a great extent
      the size distribution of microspheres.

PMID- 14727855
TI  - Orthogonal HPLC methods for quantitating related substances and degradation
      products of pramlintide.
AB  - Pramlintide is a 37-amino acid peptide that is being evaluated as a drug
      candidate for treating people with type 1 and insulin-using type 2 diabetes. Two
      high-performance liquid chromatography (HPLC) methods were developed for
      quantitating related substance impurities in pramlintide drug substance as well
      as degradation products of pramlintide formulated for parenteral administration.
      The methods differ with respect to separation mode and therefore provide
      orthogonal information concerning related substances and degradation products.
      One method uses a reverse phase (RP) separation mode, and the other involves a
      strong cation exchange (SCX) separation. Method performance testing showed that
      the RP- and SCX-HPLC methods both afford a high degree of selectivity, accuracy,
      precision, and sensitivity. The limit of quantitation for determining spiked
      authentic samples of degradation products was shown to be approximately 0.1%
      (relative to intact pramlintide) for both methods. Relative retention times for
      known pramlintide degradation products were determined for both the RP- and SCX
      HPLC methods, demonstrating the selectivities of the 2 methods as well as the
      orthogonality of the information. The methods were also shown to be
      diastereospecific with respect to separating pramlintide from authentic samples
      of D-isomers at Ala5, Ala8, Ala5-Ala8, and Leu12. The methods did not resolve
      pramlintide, however, from diastereomers with D-isomers near the C- and N
      termini, namely Lys1,Cys2, and Tyr37.

PMID- 14727857
TI  - In vivo and in vitro characterization of novel microparticulates based on
      hyaluronan and chitosan hydroglutamate.
AB  - This study examined the application of previously characterized microparticles
      composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel
      microparticles consisting of both polymers (HA/CH) to improve the nasal delivery
      of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA,
      CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively,
      compared with the control intranasal solution of gentamicin, indicating that all
      test microparticles were retained for longer periods on the nasal mucosa of the
      rabbits as supported by previous in vitro dissolution as well as frog palate
      mucoadhesion studies, thereby improving drug absorption. The higher
      bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration
      enhancing effects of CH may also be partially responsible for the improvement. A
      model was developed, based on a glass impinger device, to deliver dry powder
      formulations reproducibly onto the surface of cultured cell monolayers. In vitro
      permeability and fluorescence microscopy studies on the tight junctions of the
      16HBE14o- cell lines further confirmed the ability of CH-based formulations to
      enhance penetration. Furthermore, the in vitro absorption profile from cell
      culture studies was consistent with those determined from in vivo studies. The
      complementary effect from the mucoadhesive nature of HA coupled with the
      penetration-enhancing effects of CH makes the novel HA/CH formulation a promising
      nasal delivery system.

PMID- 14727858
TI  - Process analysis of fluidized bed granulation.
AB  - This study assesses the fluidized bed granulation process for the optimization of
      a model formulation using in-line near-infrared (NIR) spectroscopy for moisture
      determination. The granulation process was analyzed using an automated granulator
      and optimization of the verapamil hydrochloride formulation was performed using a
      mixture design. The NIR setup with a fixed wavelength detector was applied for
      moisture measurement. Information from other process measurements, temperature
      difference between process inlet air and granules (T(diff)), and water content of
      process air (AH), was also analyzed. The application of in-line NIR provided
      information related to the amount of water throughout the whole granulation
      process. This information combined with trend charts of T(diff) and AH enabled
      the analysis of the different process phases. By this means, we can obtain in
      line documentation from all the steps of the processing. The choice of the
      excipient affected the nature of the solid-water interactions; this resulted in
      varying process times. NIR moisture measurement combined with temperature and
      humidity measurements provides a tool for the control of water during fluid bed
      granulation.

PMID- 14727859
TI  - Preparation, characterization, and in vivo evaluation of salmon calcitonin
      microspheres.
AB  - PURPOSE: This study was done to prepare, characterize, and evaluate salmon
      calcitonin (sCT) microspheres (ms) in vivo using a low molecular weight,
      hydrophilic 50:50 poly (D,L-lactide-co-glycolide) polymer (PLGA). METHODS: sCT ms
      were prepared by a dispersion/solvent extraction/evaporation process and
      characterized for drug content, particle size, surface morphology, and structural
      integrity of encapsulated peptide. Peptide stability and binding to the polymer
      was studied in 0.1 M phosphate buffer (PB), pH 7.4, and 0.1 M acetate buffer
      (AB), pH 4.0. Serum sCT levels were monitored for 2 weeks after subcutaneous
      injection of sCT ms to rats. RESULTS: sCT ms were essentially free of discernible
      surface pores with a particle size distribution in the range of 16 to 89 mm and
      mean particle size of 51 and 53 mm for 2 batches. Fourier Transform Matrix
      assisted Laser Desorption mass spectrometry of the extracted peptide showed that
      the encapsulation process did not alter its chemical structure. The peptide was
      substantially more stable in AB than in PB. Peptide binding to the polymer was
      dependent on pH and was markedly higher in PB than in AB. In vivo study proved
      that elevated serum sCT levels could be sustained for at least 10 days after
      administration of sCT ms to rats at a dose of 1.0 mg/kg. CONCLUSIONS: It was
      demonstrated that sCT could be incorporated into polymeric ms prepared from a low
      molecular weight, hydrophilic PLGA using a dispersion technique without altering
      molecular structure. A 2-week formulation was prepared at a dose of 1.0 mg/kg.

PMID- 14727860
TI  - Stability of a second-generation cephalosporin veterinary mastitis formulation
      after electron beam irradiation.
AB  - This study focused on the chemical stability of the cephalosporin (6R, 7R)-7-(1
      pentafluorophenoxyacetamido)-3-[2-(5-methyl-1,3,4-thiodiazolyl)thiomethyl]
      Delta(3)-cephem-4-carboxylic acid, sodium salt (cephem 1) formulation after
      electron beam (e-beam) irradiation. The cephem 1 concentrations of samples
      irradiated at 5, 10, and 15 kilograys for glass vials and low-density
      polyethylene (LDPE) cannula syringes were not statistically different from the
      concentrations of the nonirradiated control samples. Samples from each
      irradiation dose stored in controlled-temperature chambers at 5 degrees C and 30
      degrees C for 24 months did not show any concentration changes within statistical
      limits compared with the nontreated samples. Samples from each irradiation dose
      stored at 40 degrees C for 12 months also did not show any concentration changes
      within statistical limits compared with the nontreated samples. The percentage of
      related substances increased slightly with the increase in e-beam irradiation
      level and storage temperature, but this increase was within the proposed label
      claim of 90% to 110% (45-55 mg/g). In conclusion, e-beam sterilization did not
      affect the chemical stability of cephem 1 intramammary formulation in LDPE
      cannula syringes, suggesting that e-beam irradiation may be a feasible method for
      terminal sterilization of this cephem 1 formulation.

PMID- 14727861
TI  - Influence of ibuprofen as a solid-state plasticizer in Eudragit RS 30 D on the
      physicochemical properties of coated beads.
AB  - The purpose of this study was to investigate the physicochemical properties of
      nonpareil beads coated with Eudragit RS 30 D containing ibuprofen as a
      multifunctional agent. The influence of the concentration of ibuprofen in the
      film coating and the effect of the coating level on drug release from coated
      beads was determined in pH 7.2 phosphate buffer solution. The influence of
      storage time at 23 degrees C and 60 degrees C on the release of ibuprofen from
      coated beads was also investigated. The thermal properties of the films were
      determined using a differential scanning calorimeter. Scanning electron
      microscopy was employed to image the surface morphology of the coated beads.
      Infrared spectroscopy was used to study the interaction of Eudragit RS 30 D and
      ibuprofen. Results from the dissolution studies demonstrated that increasing the
      amount of ibuprofen in the polymeric film reduced the rate of drug release,
      mainly because of a more complete coalescence of the polymeric particles of the
      latex dispersion. The glass transition temperature (Tg) of Eudragit RS 30 D films
      decreased and the surface of the coated beads became smoother as the
      concentration of ibuprofen was increased. Hydrogen bonding between the polymer
      and ibuprofen was demonstrated by Fourier transform infrared spectroscopy. No
      significant differences were found in drug dissolution between the coated beads
      stored at 23 degrees C for 12 months and those stored at 60 degrees C for 12
      hours. The results of this study demonstrated that the ibuprofen plasticized the
      Eudragit RS 30 D. Furthermore, the dissolution rate of ibuprofen can be
      controlled and changes in the drug release rate can be minimized by using the
      drug-induced plasticization technique with this polymer.

PMID- 14727862
TI  - Liposomal budesonide for dry powder inhaler: preparation and stabilization.
AB  - The purpose of the study was to prepare stable liposomally entrapped budesonide
      (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg
      phosphatidyl choline and cholesterol were prepared by lipid film hydration
      technique and sonicated to have the desired size (< 5 micro m). A rapid method
      was used for separation of free drug by centrifugation at a lower centrifugal
      force (G value). Liposomal dispersion was subjected to lyophilization after
      blending BUD with cryoprotectant in varying bulk and mass ratios, and percent
      drug remaining entrapped after lyophilization was optimized. Comparative drug
      retention studies on storage of DPI formulations were carried out in accordance
      with International Conference on Harmonization guidelines. Critical relative
      humidity of the formulations was determined and reported as one of the
      manufacturing controls. Sucrose was found to be the most effective cryoprotectant
      when present on both sides of the lamellae of liposomes in a bulk strength of 500
      mM and mass ratio of lipid:sugar; 1:10. Blending of sorbolac before
      lyophilization showed better retention of encapsulated drug (95.59%). The
      respirable fraction of the product (20.69 +/- 1.50%) was comparable with that of
      the control (26.49 +/- 1.52%), suggesting that the liposomal BUD can be
      successfully delivered throughout the broncho-pulmonary tree. The findings
      demonstrate that liposome of BUD can be prepared with a high entrapment value,
      stabilized by lyophilization, and delivered as an aerosolized DPI. The stability
      studies of lyophilized product suggests a shelf-life of one year when stored
      under refrigeration (2 degrees C-8 degrees C).

PMID- 14727863
TI  - Extrusion/spheronization of pectin-based formulations. I. Screening of important
      factors.
AB  - This study investigated the possibility of producing pectin-based pellets by
      extrusion/spheronization. The study also identified factors influencing the
      process and the characteristics of the resulting product. Three types of pectin
      with different degrees of amid and methoxyl substitution were studied in
      combination with different granulation liquids (water, calcium chloride, citric
      acid, and ethanol) and/or microcrystalline cellulose. Pellets were prepared in a
      power-consumption-controlled, twin-screw extruder; then they were spheronized and
      dried. The products were characterized by image analysis, sieving analysis, and
      disintegration and dissolution tests. The results were evaluated by multivariate
      analysis. Different additives, either in the granulation liquid or in the powder
      mixture, influenced the ability of the extruded mass to form pellets (the
      processability) with this technique. However, the various pectin types responded
      to modifications to a different extent. Short, nearly spherical pellets are
      obtained with granulation liquids, such as ethanol, that reduce the swelling
      ability of pectin. Pellets produced with ethanol are, however, mechanically weak
      and tend to disintegrate. Pectin molecules with a high degree of free carboxylic
      acid groups seem to be more sensitive to changes in the granulation liquid.
      Addition of microcrystalline cellulose as an extrusion aid generally resulted in
      improvements in shape and size. It was demonstrated that the processability of
      pectin as well as the characteristics of the products can be influenced in
      different ways during the process (eg, adding substances to the granulation
      liquid or to the powder mixture).

PMID- 14727864
TI  - Extrusion/spheronization of pectin-based formulations. II. Effect of additive
      concentration in the granulation liquid.
AB  - PURPOSE: The aim of this study was to improve the formation of spherical pectin
      pellets by investigating the effect of additive concentration in the granulation
      liquid on the shape and size of the products as well as by identifying an optimal
      additive concentration. METHODS: High-methoxylated, low-methoxylated, and
      amidated low-methoxylated pectin types were evaluated in combination with
      different concentrations of methanol, ethanol, citric acid, lactic acid, and
      calcium chloride. Pellets were prepared in a power-consumption-controlled twin
      screw extruder, then spheronized and dried. The moisture content of the extrudate
      was determined, and the final products were characterized by image analysis and
      sieving analysis. A cloud point test was employed for the identification of an
      optimal additive concentration. RESULTS: The concentration of additive in the
      granulation liquid affected the moisture content of the extrudate and the shape,
      size, and mechanical stability of the pectin pellets. Improvements in the pellet
      characteristics are dependent on the pectin type employed. The 2 low-methoxylated
      pectins were more sensitive to concentration changes than was the high
      methoxylated type. Above a certain threshold concentration, the quality of the
      pellets are improved. This additive concentration differs according to type of
      pectin and type of additive. CONCLUSION: It was demonstrated that there is a
      concentration-dependent interaction between pectin and substances added to the
      granulation liquid that can be utilized to improve the formation of spherical
      pectin pellets.

PMID- 14727865
TI  - An examination of the moisture sorption characteristics of commercial magnesium
      stearate.
AB  - The objective of this study was to characterize the moisture sorption of
      magnesium stearate and the morphological changes, if any, resulting from moisture
      sorption. Six samples of commercial magnesium stearate USP were examined.
      Moisture sorption isotherms were obtained at 25 degrees C and 5% to 98% relative
      humidity (RH) using a moisture balance. Changes in crystal form resulting from
      moisture sorption were determined by x-ray diffraction. There were differences in
      the shape of the isotherm, reversibility of moisture uptake, and shape of the
      hysteresis loop in the isotherms of crystalline and amorphous magnesium
      stearates. The isotherm of crystalline magnesium stearate was almost parallel to
      the pressure axis until an RH of ~80% was reached, when there was desorption of
      practically all of the adsorbed water. The isotherm of the amorphous sample was
      characterized by continuous uptake of water over the entire range of RH. Exposure
      of amorphous magnesium stearate to RH greater than 70% resulted in the formation
      of the trihydrate. The trihydrate was converted into the anhydrous form when
      heated to a temperature of 100 degrees C to 105 degrees C. The trihydrate could
      be generated by exposing the anhydrate to RH higher than 70%.

PMID- 14727866
TI  - Synthesis and characterization of methacrylic derivatives of 5-amino salicylic
      acid with pH-sensitive swelling properties.
AB  - The purpose of this study is to develop novel colon-specific drug delivery
      systems with pH-sensitive swelling and drug release properties. Methacrylic-type
      polymeric prodrugs with different content levels of 5-amino salicylic acid (5
      ASA) were synthesized by free radical copolymerization of metacrylic acid (MAA),
      polyethylene glycol monomethacrylate (PEGMA), and a methacrylic derivative of 5
      ASA (methacryloyloxyethyl 5-amino salicylate [MOES]). The copolymers were
      characterized, and the drug content of the copolymers was determined. The effect
      of copolymer composition on the swelling behavior and hydrolytic degradation was
      studied in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid
      (SIF, pH 7.2). The swelling and hydrolytic behavior of the copolymers was
      dependent on the content of MAA groups and caused a decrease in gel swelling in
      SGF or an increase in gel swelling in SIF. Drug release studies showed that
      increasing content of MAA in the copolymer enhances the hydrolysis in SIF but has
      no effect in SGF. The results suggest that hydrogen-bonded complexes are formed
      between MAA and PEG pendant groups and that these pH-sensitive systems could be
      useful for preparation of a controlled-release formulation of 5-ASA.

PMID- 14727867
TI  - Effect of additives on the release of a model protein from PLGA microspheres.
AB  - The purpose of this study was to investigate the effect of 2 additives,
      poly(ethylene glycol) (PEG) 1000 and 1,2,3-tridecanoyl glycerol (tricaprin), on
      the physico-chemical characteristics and in vitro release of a model protein,
      bovine serum albumin (BSA), form poly(D,L-lactic-co-glycolic acid) (PLGA)
      microspheres. BSA-loaded microspheres were prepared by the double emulsion
      solvent evaporation method. Additives were incorporated into microspheres to
      modify the release of protein. The addition of PEG 1000 and tricaprin changed the
      surface characteristics of microspheres from smooth and nonporous to porous and
      dimpled, respectively. The in vitro release profiles showed that the additives
      significantly (P < 0.05) increased the early-stage release of BSA from
      microspheres.

PMID- 14727868
TI  - Clinical assessment of the combination therapy with liposomal gels of tretinoin
      and benzoyl peroxide in acne.

PMID- 14727869
TI  - Long-term release of clodronate from biodegradable microspheres.
AB  - This paper describes the formulation of a biodegradable microparticulate drug
      delivery system containing clodronate, a bisphosphonate intended for the
      treatment of bone diseases. Microspheres were prepared with several poly(D,L
      lactide-co-glycolide) (PLGA) copolymers of various molecular weights and molar
      compositions and 1 poly(D,L-lactide) (PDLLA) homopolymer by a water-in-oil-in
      water (w/o/w) double emulsion solvent evaporation procedure. Critical process
      parameters and formulation variables (ie, addition of stabilizing agents) were
      evaluated for their effect on drug encapsulation efficiency and clodronate
      release rate from microparticles. Well-formed clodronate-loaded microspheres were
      obtained for all polymers by selecting suitable process parameters (inner
      water/oil volume ratio 1:16, temperature-raising rate in the solvent evaporation
      step 1 degree C/min, 2% wt/vol NaCl in the external aqueous phase). Good yields
      were obtained in all batches of clodronate microspheres (above 60%); drug
      encapsulation efficiencies ranged between 49% and 75% depending on the polymer
      used. Clodronate release from all copolymer microspheres was completed in about
      48 hours, while those from PDLLA microspheres required about 20 days. The change
      of microsphere composition by adding a surfactant such as Span 20 or a viscosing
      agent such as carboxymethylcellulose extended the long-term release up to 3
      months. Clodronate was successfully entrapped in PLGA and PDLLA microspheres, and
      drug release could be modulated from 48 hours up to 3 months by suitable
      selection of polymer, composition, additives, and manufacturing conditions.

PMID- 14727870
TI  - A novel method for analyzing thick tablets by near infrared spectroscopy.
AB  - A near-infrared (NIR) spectroscopic method to determine content uniformity of a
      large, thick tablet using an approach that could facilitate future validations
      has been developed. A CT ibuprofen 800-mg tablet weighs about 1150 mg and is
      about 18.6 mm wide and 7.6 mm thick. The FT NIR spectrometer was optimized for
      transmission spectra of the tablets by moving it to the sample compartment and
      placing it immediately behind the tablet. In spite of this dedicated setup, the
      transmission spectra obtained were very poor, indicating that the NIR radiation
      was not reaching the detector. The spectra of the tablet improved with use of a
      simple preparation in which a flat-face die applies pressure of 20 000 psi to the
      tablet; this reduced the thickness of the tablet from 7.6 mm to 3.6 mm. A
      calibration model was developed for tablets with drug content ranging from 70% to
      130% of label. The calibration model was tested using a validation set of tablets
      with a drug content of 752, 800, and 848 mg. The results obtained were within
      1.5% of the known drug content of the validation set tablets. Even with the
      sample preparation, the content uniformity results of 10 tablets could be
      determined using this method in less than 1 hour. The approach described in this
      article could also be used to validate NIR content uniformity methods for other
      formulations.

PMID- 14727871
TI  - Low-temperature micronization of a peptide drug in fluid propellant: case study
      cetrorelix.
AB  - Aim of this study was to elaborate an efficient method for the micronization of
      the decapeptide cetrorelix (a GnRH-antagonist), in order to obtain a
      microsuspension as basis for other pharmaceutical preparations, such as e.g.
      inhalation aerosols. A modified pearl-mill coupled with a cryostat was used for
      the micronization of cetrorelix in fluid propellant and operated under different
      conditions. The obtained cetrorelix suspensions were analyzed for particle size
      distribution, purity of cetrorelix, and for metal contamination through abrasion
      from parts of the mill. The method allowed an effective micronization of
      cetrorelix. The mean particle size of the initial cetrorelix lyophilizate bulk
      ware was reduced from 52.5 microm (Volume Mean Diameter, VMD) down to 14.9, 6.1
      and 3.1 microm, respectively, respectively. The HPLC analysis of all cetrorelix
      suspensions after micronization did not show signs of decomposition as compared
      to the initial product. The elementary analysis of the suspensions performed by
      inductively coupled plasma mass spectrometry revealed a negligible amount of
      contaminants in the suspension (Zr = max. 0.6 ppm; Fe, Cr, Ni, Ba, below limit of
      quantification, i.e. < 0.14 ppm). The only appreciable contaminant, Aluminum (Al
      = 1.1 ppm), was derived from the mechanical capping of aluminum canisters prior
      to analysis. The Zr determination in the suspension of 0.6 ppm, is still
      considered to be negligible as compared to the legally tolerated limit of air
      contamination. By low-temperature micronization in fluid propellant, fine drug
      suspensions of cetrorelix for pMDIs can be directly manufactured in one-step
      procedure without destruction of the peptide structure and without appreciable
      product contamination.

PMID- 14727872
TI  - Evaluation of an acetic acid ester of monoglyceride as a suppository base with
      unique properties.
AB  - The objective of this investigation was to evaluate an acetic acid ester of
      monoglycerides made from edible, fully hydrogenated palm oil (AC-70) as a
      suppository base and compare it with a commercially available semisynthetic base
      (Suppocire AI). Benzocaine and miconazole were used as model drugs. Suppositories
      were prepared by the fusion method. The drug loads in the suppositories were kept
      at 2% to 5% (wt/wt). In vitro release of drug from the suppositories into
      Sorensen's phosphate buffer (pH 7.4) was studied using a US Pharmacopeia
      dissolution apparatus 1 and a spectrophotometer. The melting behavior of the
      bases and the physical state of the drug in the suppositories were studied using
      a differential scanning calorimeter (DSC). Powder x-ray diffractometry was used
      to study any possible polymorphic changes in the AC-70 base during formulation
      and storage. In vitro release studies revealed that the release of benzocaine
      from the AC-70 suppository was substantially slower than that of the commercial
      AI base. At a 2.5% (wt/wt) benzocaine load, the release of drug from the AC-70
      suppositories was found to be linear. This slow and linear release was attributed
      to the physical property of the base, which forms liquid crystalline phases in
      the aqueous dissolution medium. The lyotropic liquid crystalline phase has the
      ability to incorporate drug into its structure and can control the release
      kinetics of the drug from such a system. The apparent pH of the release medium
      (water) was decreased by 1 to 1.5 pH units when the AC-70 base was used. The DSC
      studies revealed that the melting range of the AC-70 base is 36 degrees C to 38
      degrees C, which is ideal for suppository formulations. The results of these
      studies support the possibility of using this new base for slow-release
      suppository formulations. This base may be of particular interest for a drug that
      requires an acidic environment to maintain its activity.

PMID- 14727873
TI  - Pharmaceutical development and manufacturing of a parenteral formulation of a
      novel antitumor agent, VNP40101M.
AB  - The objective of this study was to develop and manufacture a stable parenteral
      formulation for Phase I clinical trials of VNP40101M (1,2-Bis(methylsulfonyl)-1
      (2-chloroethyl)-2-[(2-methylamino)carbonyl] hydrazine), a novel antitumor agent.
      The solubility and stability of the drug was determined. Solubility studies
      suggested that VNP40101M exhibited poor aqueous solubility but showed appreciable
      solubility in nonaqueous solvents. The aqueous solubility of the drug could not
      be increased by adjusting the pH. At a pH above 7, base-catalyzed decomposition
      of VNP40101M occurred. The low octanol-water partition coefficient of 0.75
      suggested poor solubility in lipophilic solvents. Based on these preformulation
      observations, a parenteral formulation containing 10 mg/mL of VNP40101M was
      prepared in a solvent system consisting of 30% ethyl alcohol and 70% polyethylene
      glycol-300 (PEG-300). To minimize base-catalyzed hydrolytic degradation, citric
      acid at 0.6% concentration was included to acidify the formulation. Rubber
      closures, filter membranes, and liquid transfer tubing were selected on the basis
      of compatibility studies and absence of loss of drug due to adsorption of these
      components. The formulation was subjected to accelerated stability studies and
      dilution studies with large volume parenteral (LVP) solutions, normal saline, and
      5% dextrose injection (D5W). The results of the dilution study indicated that the
      formulation could be diluted in these solutions up to 2 mg/mL for 8 hours without
      drug precipitation and degradation. Accelerated stability studies suggested that
      the product should be kept at 2 degrees C to 8 degrees C for long-term storage.
      The developed formulation was successfully scaled up and manufactured for use in
      clinical trials.

PMID- 14727874
TI  - Improved function of rat islets upon co-microencapsulation with Sertoli's cells
      in alginate/poly-L-ornithine.
AB  - The purpose of this study was to assess whether Sertoli's cells would improve
      functional performance of homologous pancreatic islets within microcapsules.
      Purified rat Sertoli's cells were co-enveloped with islets in microcapsules that
      had been fabricated with alginic acid and poly-L-ornithine. Confocal laser
      microscopy was used to determine any mitogenic effects of Sertoli's cells on
      islets beta-cells. Insulin secretion from islets, with or without Sertoli's
      cells, was examined, and grafts of Sertoli's cells with islets in microcapsules
      into diabetic mice were carried out. Co-incubation of Sertoli's cells with islets
      resulted in a significant increase in the islet beta-cell mitotic rate, which was
      coupled with significantly higher insulin release under glucose stimulation, as
      compared to controls. Grafts of co-microencapsulated Sertoli's cells with islets
      resulted in prolongation of the achieved normoglycemia in the animals receiving
      Sertoli's cells with islets as compared to controls that received islets only.
      Sertoli's cells do promote mitogenic activities upon in vitro co-incubation with
      islets, whose in vitro functional and in vivo post-transplant consequences were
      evident. Sertoli's cells could, therefore, be co-microencapsulated with islets
      for transplantation in diabetic recipients.

PMID- 14727876
TI  - Porous bone morphogenetic protein-2 microspheres: polymer binding and in vitro
      release.
AB  - This research compared the binding and release of recombinant human bone
      morphogenetic protein 2 (rhBMP-2) with a series of hydrophobic and hydrophilic
      poly-lactide-co-glycolide (PLGA) copolymers. Porous microspheres were produced
      via a double emulsion process. Binding and incorporation of protein were achieved
      by soaking microspheres in buffered protein solutions, filtering, and comparing
      protein concentration remaining to nonmicrosphere-containing samples. Protein
      release was determined by soaking bound microspheres in a physiological buffer
      and measuring protein concentration (by reversed-phase high-performance liquid
      chromatography) in solution over time. Normalized for specific surface area and
      paired by polymer molecular weight, microspheres made from hydrophilic 50:50 or
      75:25 PLGA bound significantly more protein than microspheres made from the
      corresponding hydrophobic PLGA. Increased binding capacity correlated with higher
      polymer acid values. With certain polymers, rhBMP-2 adsorption was decreased or
      inhibited at high protein concentration, but protein loading could be enhanced by
      increasing the protein solution:PLGA (volume:mass) ratio or by repetitive
      soaking. Microspheres of various PLGAs released unbound protein in 3 days,
      whereas the subsequent bound protein release corresponded to mass loss. RhBMP-2
      binding to PLGA was controlled by the acid value, protein concentration, and
      adsorption technique. The protein released in 2 phases; the first occurred over 3
      days regardless of PLGA used and emanated from unbound, incorporated protein,
      while the second was controlled by mass loss and therefore was dependent on the
      polymer molecular weight. Overall, control of rhBMP-2 delivery is achievable by
      selection of PLGA microsphere carriers.

PMID- 14727875
TI  - In vitro and in vivo evaluations of biodegradable implants for hormone
      replacement therapy: effect of system design and PK-PD relationship.
AB  - This investigation evaluated the feasibility of using subdermally implantable
      devices fabricated by nonconventional 3-dimensional printing technology for
      controlled delivery of ethinyl estradiol (EE2). In vitro release kinetics of EE2
      and in vivo pharmacokinetics/pharmacodynamics in ovariectomized New Zealand White
      rabbits were carried out to study 3 implant prototypes: implant I (single-channel
      EE2 distribution in polycaprolactone polymer core), implant II (homogeneous EE2
      distribution in polycaprolactone polymer matrix), and implant III (concentration
      gradient EE2 distribution in polycaprolactone and poly(dl-lactide-co-glycolide)
      (50:50 matrix). EE2 was found to be released from all the implants in a nonlinear
      pattern with an order of implant III > implant II > implant I. The
      noncompartmental pharmacokinetic analysis of plasma EE2 profiles in rabbits
      indicated a significant difference (p < .05) in Cmax, tmax, and mean residence
      time between implant I and implants II and III, but no difference in the area
      under the plasma concentration time curves calculated by trapezoidal rule (AUC)
      among the implants. For pharmacodynamic studies, endogenous follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) levels were observed to be suppressed
      following implantation of all implants, which demonstrated that a therapeutically
      effective dose of EE2 had been delivered. Furthermore, the noncompartmental
      analysis of plasma FSH and LH profiles in rabbits showed a significant difference
      (p < .05) in AUC and the mean residence time between implant III and implants I
      and II. A good in vivo/in vitro relationship was observed between daily amounts
      of EE2 released and plasma profiles of EE2 for all implants. This relationship
      suggests that plasma profiles of EE2 could be predicted from in vitro measurement
      of daily amount of EE2 released. Therefore, performing in vitro drug release
      studies may aid in the development of an EE2 implant with the desired in vivo
      release rate.

PMID- 14727877
TI  - Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.
AB  - The hypothesis of this research was that implants of poly(lactide-co-glycolide)
      (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and
      distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce
      more new bone than would matrix implants of non-protein-loaded microspheres or
      matrix implants of only CMC. To test this hypothesis it was necessary to fashion
      microsphere-loaded CMC implants that were simple to insert, fit precisely into a
      defect, and would not elicit swelling. Microspheres were produced via a water-in
      oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them
      in a buffered solution of the protein at a concentration of 5.4 mg protein per
      gram of PLGA. Following recovery of the loaded microspheres by lyophilization,
      matrices for implantation were prepared by lyophilizing a suspension of the
      microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices
      were made with 2% CMC and with 2% CMC containing blank microspheres. A full
      thickness calvarial defect model in New Zealand white rabbits was used to assess
      bone growth. Implants fit the defect well, allowing for direct application. Six
      weeks postsurgery, defects were collected and processed for undecalcified
      histology. In vitro, 60% of the loaded rhBMP-2 released from devices or
      microspheres in 5 to 7 days, with the unembedded microspheres releasing faster
      than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced
      bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little
      effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres
      in CMC was an effective implantable protein-delivery system for use in bone
      repair.

PMID- 14727878
TI  - In vitro assessment of alkylglycosides as permeability enhancers.
AB  - series of alkylglycosides has been evaluated on human cell lines to determine its
      ability to open cellular tight junctions. Alkylglycosides were applied to cell
      monolayers; the resulting change in resistance was determined by transepithelial
      electrical resistance measurements. Change in resistance across cell monolayers
      is an indication of tight junction activation, whereas subsequent increase in
      resistance signifies monolayer recovery. Of the 13 alkylglycosides tested, 4
      caused irreversible solubilization of cell membranes, 5 allowed a partial
      recovery of the monolayer after a relatively rapid reduction in resistance, and 4
      induced a decrease in resistance with more complete cell recovery.
      Alkylglycosides allowing extensive cell recovery after removal may indicate tight
      junctions' activity dominance over membrane fluidity. Repeated application of
      alkylglycosides for 6 hours lowered resistance across cells, which returned to
      near-normal values after a recovery period of 48 hours. A model dye was
      transported across the cell monolayer only in the presence of an alkylglycoside,
      although recovery of cells was incomplete. Activity of the alkylglycosides was
      unrelated to either the carbon chain length or to the carbohydrate moiety. A
      direct correlation was established between the concentration of applied
      alkylglycoside and reduction in resistance over a constant time period.
      Dodecylmaltoside and octylglucoside were found to be optimal in decreasing
      resistance at low concentrations and allowing significant recovery of cells.
      Therefore these 2 alkylglycosides may be useful in facilitating drug transport
      across biological membranes.

PMID- 14727879
TI  - Freeze-drying of microparticulates in a vibro-separator.

PMID- 14727880
TI  - GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion.
AB  - In a systematic effort to develop a dual-function intravaginal spermicide as well
      as a drug delivery vehicle against sexually transmitted pathogens, a submicron
      particle size (30-80 nm), lipophilic and spermicidal gel-microemulsion (viz GM
      144) containing the pharmaceutical excipients propylene glycol, Captex 300,
      Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was
      formulated. GM-144 completely immobilized sperm in human or rabbit semen in less
      than 30 seconds. Therefore, the in vivo contraceptive potency of intravaginally
      applied GM-144 was compared in the standard rabbit model to those of the
      detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four
      ovulated New Zealand White rabbits in subgroups of 28 were artificially
      inseminated with and without intravaginal administration of GM-144 or 2% N-9
      (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed
      remarkable contraceptive activity in the rigorous rabbit model. When compared
      with control, intravaginal administration of GM-144 and Gynol II resulted in 75%
      and 70.8% inhibition of fertility (P <.0001 versus control, Fisher's exact test),
      respectively. Thus, GM-144 as a vaginal contraceptive was as effective as the
      commercially available N-9 gel. In the rabbit vaginal irritation test, none of
      the 6 rabbits given daily intravaginal application of spermicidal GM-144 for 10
      days developed epithelial ulceration, edema, leukocyte influx, or vascular
      congestion characteristic of inflammation (total score = 5). Therefore, GM-144
      has the potential to become a clinically useful safe vaginal contraceptive and a
      vehicle for formulating lipophilic drugs used in reducing the risk of
      heterosexual transmission of sexually transmitted diseases.

PMID- 14727881
TI  - Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen
      release from sustained-release tablets.
AB  - The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose
      [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers
      (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium
      carbonate, and sodium citrate) on naproxen release rate was studied. Matrix
      tablets were prepared by double compression, and in vitro dissolution tests were
      performed. The dissolution results showed that an increased amount of HPMC or
      hydrogenated castor oil resulted in reduced drug release. The inclusion of
      buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets,
      only sodium bicarbonate enhanced naproxen release. The presence of lactose on
      HPMC matrix tablets did not show a significantly different result from that
      obtained with the formulation containing dibasic calcium phosphate as a filler.
      However, for the tablets containing HCO, the presence of lactose significantly
      enhanced the naproxen release rate. The matrix-forming materials in this study
      were suitable for use in sustained-release tablets containing naproxen. The drug
      release can be modulated by adding suitable amounts of diluents and buffers.

PMID- 14727882
TI  - Compression, compaction, and disintegration properties of low crystallinity
      celluloses produced using different agitation rates during their regeneration
      from phosphoric acid solutions.
AB  - The tabletting characteristics of low crystallinity celluloses (LCPC)-LCPC-700,
      LCPC-2000, and LCPC-4000-prepared using agitation rates of 700, 2000, and 4000
      rpm, respectively, during their regeneration from phosphoric acid, were evaluated
      and compared with those of Avicel PH-102 and Avicel PH-302. The mean deformation
      pressure values calculated from the linear region of the Athy-Heckel curves
      indicated LCPC-4000 to be the most ductile material. The area under the Athy
      Heckel curve for LCPC-4000 was 330 MPa, whereas LCPC-700 and LCPC-2000 showed a
      corresponding value similar to that of Avicel PH-102 and Avicel PH-302 (192-232
      MPa). The tensile strength of LCPC and Avicel compacts increased linearly with
      increasing applied pressures. A comparison of the area under the tensile strength
      compression pressure curves indicated that LCPC-4000 formed the strongest
      tablets. The strengths of LCPC-700 and LCPC-2000 compacts, in contrast, were
      slightly lower than that of Avicel PH-302 and Avicel PH-102, respectively. The
      compacts of both LCPC-4000 and Avicel PH-102 were intact in water for 6 hours,
      whereas LCPC-2000 and Avicel PH-302 compacts disintegrated in 4 minutes and 2
      minutes, respectively. In conclusion, LCPC-4000 was the most ductile material and
      exhibited the highest compression and compaction characteristics. The
      corresponding properties of LCPC-700 and LCPC-2000, in contrast, were comparable
      to that of Avicel PH-102 or Avicel PH-302.

PMID- 14727883
TI  - Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix
      tablets.
AB  - A reverse-phase high-performance liquid chromatographic (HPLC) method for
      recovery of the lipophilic drug, alprazolam, from matrix tablets containing the
      hydrophilic polymer hydroxypropyl methylcellulose (HPMC) was developed.
      Lipophilic drugs, such as alprazolam, are difficult to completely extract and
      quantitate from tablets containing HPMC polymer. The percentage of recoveries of
      alprazolam from placebo powder spiked with alprazolam stock solution and from
      placebo powder mixed with alprazolam powder were about 100% and 85% to 95%,
      respectively. The validated method using water to completely dissolve HPMC before
      the addition of a strong solvent to dissolve and extract the drug from the HPMC
      solution was shown to be the most reproducible method. Different molecular weight
      distributions of the HPMC polymer, such as HPMC-K4M and HPMC-K100LV, did not
      influence the dissolution results of alprazolam using this validated method.
      Similarly, the excipients composing the matrix tablet formulations, such as
      dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium sulfate
      dihydrate, sucrose, dextrose, and lactose monohydrate, did not influence the
      percent recovery of alprazolam. The recovery method reported herein was shown to
      be the most efficient to achieve complete recovery of alprazolam from powder
      blends and tablets containing a variety of excipients and different grades of
      HPMC.

PMID- 14727884
TI  - Multispectral imaging of tablets in blister packaging.
AB  - This experiment tested the hypothesis that using near-infrared (IR) imaging
      spectrometry on tablets through blister packs permits the identification and
      composition of multiple individual tablets to be determined simultaneously.
      Aspirin was selected for this study because its breakdown mechanism is well
      understood. Near-IR cameras were used to collect thousands of spectra
      simultaneously from a field of packaged aspirin tablets. Tablets were selected by
      a principal component analysis selection algorithm. Graphs of the columns of the
      transformation matrix showed that salicylic acid and acetylsalicylic acid in the
      samples were modeled by the principal components. The bootstrap error-adjusted
      single-sample technique chemometric-imaging algorithm was used to draw
      probability-density contour plots that revealed tablet composition. Choice of
      color was used to represent constituent identity, whereas intensity represented
      concentration. The percentage of usable pixels in the indium antimonide (InSb)
      array was 99.9%. The SEP was 0.06% of the tablet mass for both water uptake and
      salicylic acid production. The number of tablets that a typical near-IR camera
      can currently analyze simultaneously was also estimated to be approximately 1300.

PMID- 14727885
TI  - Physical and chemical permeation enhancers in transdermal delivery of terbutaline
      sulphate.

PMID- 14727886
TI  - Use of PharmASep unit for processing microspheres.

PMID- 14727887
TI  - Statistical optimization of gastric floating system for oral controlled delivery
      of calcium.
AB  - The development of an optimized gastric floating drug delivery system is
      described. Statistical experimental design and data analysis using response
      surface methodology is also illustrated. A central, composite Box-Wilson design
      for the controlled release of calcium was used with 3 formulation variables: X1
      (hydroxypropyl methylcellulose [HPMC] loading), X2 (citric acid loading), and X3
      (magnesium stearate loading). Twenty formulations were prepared, and dissolution
      studies and floating kinetics were performed on these formulations. The
      dissolution data obtained were then fitted to the Power Law, and floating
      profiles were analyzed. Diffusion exponents obtained by Power Law were used as
      targeted response variables, and the constraints were placed on other response
      variables. All 3 formulation variables were found to be significant for the
      release properties (P <.05), while only HPMC loading was found to be significant
      for floating properties. Optimization of the formulations was achieved by
      applying the constrained optimization. The optimized formulation delivered
      calcium at the release rate of 40 mg/hr, with predicted n and T50% values at 0.93
      and 3.29 hours, respectively. Experimentally, calcium was observed to release
      from the optimized formulation with n and T50% values of 0.89 (+/- 0.10) and 3.20
      (+/- 0.21) hours, which showed an excellent agreement. The quadratic mathematical
      model developed could be used to further predict formulations with desirable
      release and floating properties.

PMID- 14727888
TI  - Adsorption of allopurinol and ketotifen by chitosan.
AB  - The experimental work of studying the adsorption of ketotifen and allopurinol by
      chitosan focused on determining the solubilities and the adsorption isotherms of
      the adsorbates employed in this study. The adsorption of the aforementioned
      compounds by chitosan was studied using the rotating bottle method. The
      concentrations, both before and after the attainment of equilibrium, were
      determined with the aid of a reversed-phase high-performance liquid
      chromatography column. The results of these studies demonstrated that ketotifen
      and allopurinol are both adsorbed by chitosan. The nonlinear Langmuir-like and
      the Freundlich models both were applied to the experimental data. The correlation
      coefficients obtained from the nonlinear Langmuir-like model were better than
      those obtained from Freundlich model, suggesting that allopurinol and ketotifen
      interacted with certain specific binding sites on the chitosan surface. The
      allopurinol adsorption experiments indicated that the particle size of chitosan
      and therefore the surface area can significantly affect the Langmuir capacity
      constant, while the affinity constants are statistically the same. As expected
      from the solubility studies, the ketotifen adsorption experiments at 2 different
      pHs (7 and 10) showed that the adsorption affinity at pH 10 was much higher than
      at pH 7. What was not expected was that the capacity constants were significantly
      different, suggesting that further studies are needed using common ion buffers
      and multicomponent adsorption for the proper mechanism to be determined.

PMID- 14727889
TI  - Evaluation of preseparator performance for the 8-stage nonviable andersen
      impactor.
AB  - The preseparator of an Andersen impactor with different coating treatments for a
      range of particle-size distributions was evaluated. Limited theoretical
      simulations constrained by simplifying assumptions of the airflow fields in the
      preseparator and upper stages of an 8-stage Andersen impactor were used to reveal
      low-velocity and high-pressure regions for potential deposition. These regions
      were then sampled in subsequent particle deposition experiments. Disodium
      fluorescein aerosols were sampled with different coating treatments of the
      preseparator floor. Particles collected at impactor stages determined particle
      size distributions. Stage deposition was compared between different preseparator
      treatments (buffer and silicon oil). Collection efficiency in the preseparator
      followed the pattern buffer > silicon oil > untreated. Statistical differences (P
      < 0.05) were noted in collection efficiency of large particles (45 micro m-75
      microm) in the preseparator. The mass median aerodynamic diameters and geometric
      standard deviations showed some statistical differences when different
      preseparator treatments for large particles were used; therefore, preseparator
      coating was shown to influence performance and thereby estimates of particle size
      by inertial impaction.

PMID- 14727890
TI  - Solubilization of cyclosporin A.
AB  - This study investigated the solubilization of cyclosporin A (CsA), a neutral
      undecapeptide, by cosolvency, micellization, and complexation. Cosolvents
      (ethanol, propylene glycol, polyethylene glycol, tetrahydrofurfuryl alcohol
      polyethyleneglycol ether, and glycerin), surfactants (polyoxyethylene sorbitan
      monooleate [(Tween 80)], polyoxyethylene sorbitan monolaurate [(Tween 20)], and
      Cremophor EL), and cyclodextrins (alpha-cyclodextrin [(alphaCD)] and
      hydroxypropyl-beta-cyclodextrin[(HPbetaCD)] were used as solubilizing agents in
      this study. Surfactants had a noticeable effect in increasing CsA solubility.
      Twenty percent solutions of Tween 20, Tween 80, and Cremophor EL increased the
      solubility by 60 to 160 fold. Cyclodextrins can increase the CsA solubility, but
      alphaCD was more effective than HPbetaCD. Cosolvents on the other hand did not
      increase the solubility of CsA as much as expected from the LOGP (logarithm of
      water-octanol partition coefficient) value of CsA.

PMID- 14727891
TI  - Importance of inlet air velocity in fluid bed drying of a granulation prepared in
      a high shear granulator.

PMID- 14727892
TI  - Evaluation of Orntide microspheres in a rat animal model and correlation to in
      vitro release profiles.
AB  - Orntide acetate, a novel luteinizing hormone-releasing hormone (LHRH) antagonist,
      was prepared and evaluated in vivo in 30-day and 120-day sustained delivery
      formulations using a rat animal model. Orntide poly(d,l-lactide-co-glycolide)
      (PLGA) and poly(d,l- lactide) (PLA) microspheres were prepared by a dispersion
      method and administered subcutaneously in a liquid vehicle to rats at 2.2 mg
      Orntide/kg of body weight (30-day forms) or 8.8 mg Orntide/kg (120-day forms).
      Serum levels of Orntide and testosterone were monitored by radioimmunoassays, and
      a dose-response study at 4 doses (3, 2.25, 1.5, and 1.75 mg Orntide/kg) was
      conducted to determine the effective dose of Orntide. Microspheres with diameters
      between 3.9 and 14 micron were prepared. The onset and duration of testosterone
      suppression varied for different microsphere formulations and were influenced
      both by polymer properties and by microsphere characteristics. Microspheres
      prepared with 50:50 and 75:25 copolymers effectively sustained peptide release
      for 14 to 28 days, whereas an 85:15 copolymer and the PLA microspheres extended
      the pharmacological response for more than 120 days. Increase in drug load
      generally accelerated peptide release from the microspheres, resulting in higher
      initial serum levels of Orntide and shorter duration of the release. In general,
      apparent release was faster in vivo than under in vitro conditions. Orntide
      microspheres effectively suppressed testosterone in rats, providing rapid onset
      of release and extended periods of chemical castration. Testosterone suppression
      occurred immediately after microsphere administration without the initial
      elevation seen with LHRH superagonists.

PMID- 14727893
TI  - Formulation and in vitro transfection efficiency of poly (D, L-lactide-co
      glycolide) microspheres containing plasmid DNA for gene delivery.
AB  - The stability, in vitro release, and in vitro cell transfection efficiency of
      plasmid DNA (pDNA) poly (D,L-lactide-co-glycolide) (PLGA) microsphere
      formulations were investigated. PLGA microspheres containing free and polylysine
      (PLL)-complexed pDNA were prepared by a water-oil-water solvent
      extraction/evaporation technique. Encapsulation enhanced the retention of the
      supercoiled structure of pDNA as determined by gel electrophoresis. PLL
      complexation of pDNA prior to encapsulation increased both the stability of the
      supercoiled form and the encapsulation efficiency. Free pDNA was completely
      degraded after exposure to DNase, while encapsulation protected the pDNA from
      enzymatic degradation. Rapid initial in vitro release of pDNA was obtained from
      microspheres containing free pDNA, while the release from microspheres containing
      PLL-complexed pDNA was sustained for more than 42 days. Bioactivity of
      encapsulated pDNA determined by in vitro cell transfection using Chinese hamster
      ovary cells (CHO) showed that the bioactivity of encapsulated pDNA was retained
      in both formulations but to a greater extent with PLL-complexed pDNA
      microspheres. These results demonstrated that PLGA microspheres could be used to
      formulate a controlled-release delivery system for pDNA that can protect the pDNA
      from DNase degradation without loss of functional activity.

PMID- 14727894
TI  - A bioresorbable, polylactide reservoir for diffusional and osmotically controlled
      drug delivery.
AB  - The purpose of this study was to design and characterize a zero-order
      bioresorbable reservoir delivery system (BRDS) for diffusional or osmotically
      controlled delivery of model drugs including macromolecules. The BRDS was
      manufactured by casting hollow cylindrical poly (lactic acid) (PLA): polyethylene
      glycol (PEG) membranes (10 x 1.6 mm) on a stainless steel mold. Physical
      properties of the PLA:PEG membranes were characterized by solid-state thermal
      analysis. After filling with drug (5 fluorouracil [5FU] or fluorescein
      isothiocyanate [FITC]-dextran:mannitol, 5:95 wt/wt mixture) and sealing with
      viscous PLA solution, cumulative in vitro dissolution studies were performed and
      drug release monitored by ultraviolet (UV) or florescence spectroscopy.
      Statistical analysis was performed using Minitab (Version 12). Differential
      scanning calorimetry thermograms of PLA:PEG membranes dried at 25 degrees C
      lacked the crystallization exotherms, dual endothermal melting peaks, and
      endothermal glass transition observed in PLA membranes dried at -25 degrees C. In
      vitro release studies demonstrated zero-order release of 5FU for up to 6 weeks
      from BRDS manufactured with 50% wt/wt PEG (drying temperature, 25 degrees C). The
      release of FITC dextrans of molecular weights 4400, 42 000, 148 000, and 464 000
      followed zero-order kinetics that were independent of the dextran molecular
      weight. When monitored under different concentrations of urea in the dissolution
      medium, the release rate of FITC dextran 42 000 showed a linear correlation with
      the calculated osmotic gradient(DeltaPi). This study concludes that PEG inclusion
      at 25 degrees C enables manufacture of uniform, cylindrical PLA membranes of
      controlled permeability. The absence of molecular weight effects and a linear
      dependence of FITC-dextran release rate on DeltaPi confirm that the BRDS can be
      modified to release model macromolecules by an osmotically controlled mechanism.

PMID- 14727895
TI  - Formulation variables affecting drug release from xanthan gum matrices at
      laboratory scale and pilot scale.
AB  - The purpose of this research was to study processing variables at the laboratory
      and pilot scales that can affect hydration rates of xanthan gum matrices
      containing diclofenac sodium and the rate of drug release. Tablets from the
      laboratory scale and pilot scale proceedings were made by wet granulation.
      Swelling indices of xanthan gum formulations prepared with different amounts of
      water were measured in water under a magnifying lens. Granules were thermally
      treated in an oven at 60 degrees C, 70 degrees C, and 80 degrees C to study the
      effects of elevated temperatures on drug release from xanthan gum matrices.
      Granules from the pilot scale formulations were bulkier compared to their
      laboratory scale counterparts, resulting in more porous, softer tablets. Drug
      release was linear from xanthan gum matrices prepared at the laboratory scale and
      pilot scales; however, release was faster from the pilot scales. Thermal
      treatment of the granules did not affect the swelling index and rate of drug
      release from tablets in both the pilot and laboratory scale proceedings. On the
      other hand, the release from both proceedings was affected by the amount of water
      used for granulation and the speed of the impeller during granulation. The data
      suggest that processing variables that affect the degree of wetness during
      granulation, such as increase in impeller speed and increase in amount of water
      used for granulation, also may affect the swelling index of xanthan gum matrices
      and therefore the rate of drug release.

PMID- 14727896
TI  - Novel mathematical method for quantitative expression of deviation from the
      higuchi model.
AB  - A simple mathematical method to express the deviation in release profile of a
      test product following Higuchi's kinetics from an ideal Higuchi release profile
      was developed. The method is based on calculation of area under the curve (AUC)
      by using the trapezoidal rule. The precision of prediction depends on the number
      of data points. The method is exemplified for 2 dosage forms (tablets of
      diltiazem HCl and microspheres of diclofenac sodium) that are designed to release
      the drug over a 12-hour period. The method can be adopted for the formulations
      where drug release is incomplete (<100%) or complete (100%) at last sampling
      time. To describe the kinetics of drug release from the test formulation, zero
      order, first-order, Higuchi's, Hixson-Crowell's, and Weibull's models were used.
      The criterion for selecting the most appropriate model was based on the goodness
      of-fit test. The release kinetics of the tablets and microspheres were explained
      by the Higuchi model. The release profiles of the test batches were slightly
      below the ideal Higuchi release profile. For the test products, observed
      percentage deviation from an ideal Higuchi profile is less than 16% for tablets
      and less than 11% for microspheres. The proposed method can be extended to the
      modified release formulations that are designed to release a drug over 6, 18, or
      24 hours. If the data points are not evenly separated, the ideal drug release
      profile and AUC are calculated according to the specific sampling time. The
      proposed method may be used for comparing formulated products during the research
      and development stage, for quality control of the products, or for promoting
      products by comparing performance of the test product with that of the
      innovator's product.

PMID- 14727897
TI  - Effect of isopropyl myristic acid ester on the physical characteristics and in
      vitro release of etoposide from PLGA microspheres.
AB  - The purpose of this paper was to study the effect of the isopropyl myristic acid
      ester (IPM) on the physicochemical characteristics of etoposide-loaded
      poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on
      the size and drug loading of the microspheres, the polymer matrix and surface
      morphology, and the release of etoposide from the microspheres. The experiment
      was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no
      IPM) at 2 different etoposide-loading percentages (10% and 5%). The microspheres
      were prepared using a single-emulsion solvent-extraction procedure. Samples from
      each batch of microspheres were then analyzed for size distribution, drug-loading
      efficiency, surface characteristics, in vitro release, and in vitro microsphere
      degradation. The incorporation of 50% IPM significantly increased (P <.05) the
      size of the microspheres when compared with the control and 25% IPM microspheres.
      However, incorporation of 25% or 50% IPM did not change (P >.05) the drug-loading
      efficiency in comparison with the microspheres prepared without IPM. The
      microspheres containing 50% IPM were shown to significantly increase (P <.05) the
      release of etoposide from the microspheres at both etoposide concentrations. The
      microspheres prepared incorporating 25% IPM and 5% etoposide increased the in
      vitro release (P <.05) in comparison with the microspheres prepared without IPM.
      The 5% etoposide-PLGA microspheres showed a smooth, nonporous surface that
      changed to a dimpled, nonporous surface after addition of 25% IPM. During the in
      vitro degradation study, the IPM-containing microspheres slowly became porous but
      retained their structural integrity throughout the experiment.

PMID- 14727898
TI  - Effect of drug substance particle size on the characteristics of granulation
      manufactured in a high-shear mixer.
AB  - DPC 963 is a non-nucleoside reverse transcriptase inhibitor with low aqueous
      solubility. The effect of DPC 963 drug substance particle size on the
      characteristics of granules manufactured by high-shear wet granulation was
      evaluated. The wet granulation process was used to manufacture a DPC 963
      formulation with high drug loading. The formulation was manufactured using drug
      substance lots with different particle size distributions. Granulation particle
      size distribution, porosity, and compressibility were determined. A uniaxial
      compression test was also performed on moist compacts of the formulation prepared
      with different particle size distributions. Particle agglomeration behavior was
      affected by drug substance particle size. Granulation geometric mean diameter and
      fraction with particle size greater than 250 microm was inversely proportional to
      the drug substance particle size. Mercury intrusion porosimetry revealed higher
      pore volumes for the granules manufactured using the drug substance with the
      smaller particle size, suggesting lower tendency for granule densification than
      for that manufactured with the larger drug substance particle size. Granulation
      compressibility was also sensitive to changes in drug substance particle size. A
      decreased drug substance particle size led to increased granulation
      compressibility. Results from the uniaxial compression experiments suggested that
      the effect of particle size on granulation growth is the result of increased
      densification propensity, which in turn results from increased drug substance
      particle size.

PMID- 14727899
TI  - Development and evaluation of oral multiple-unit and single-unit hydrophilic
      controlled-release systems.
AB  - This study compared the release behavior of single-unit (tablets, capsules) and
      multiple-unit (minitablets in capsules) controlled-release systems of furosemide.
      The swelling and erosion behaviors of these systems, which contained the
      swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol
      974P, were compared. Swelling and erosion experiments showed a high degree of
      swelling and limited erosion for the Carbopol preparations, whereas less swelling
      but greater erosion was observed for the sodium alginate preparations. The sodium
      alginate preparations were eroded in 6 hours, while Carbopol preparations
      exhibited limited erosion within this period of time. These results appear to be
      attributed to the physicochemical characteristics of the polymers used in this
      study. Polymer characteristics greatly influenced the release of furosemide
      (model drug) from the formulations prepared and tested. Sodium alginate had a
      less pronounced sustained release effect compared with Carbopol (ie, in 8 hours
      all 3 sodium alginate dosage forms displayed complete release of furosemide,
      while only 30% of the drug was released from Carbopol dosage forms). Finally, all
      3 Carbopol dosage forms (single- and multiple-unit) displayed similar release
      behavior while sodium alginate dosage forms displayed a different and more
      distinctive behavior. Minitablets and tablets showed a greater sustained release
      effect compared with capsules. Evaluation of the release data indicates that the
      release mechanism for sodium alginate formulations may be attributed to
      erosion/dissolution, while for Carbopol it may be attributed mainly to polymer
      relaxation and diffusion of the drug from the polymer surface.

PMID- 14727900
TI  - Optimization of the pelletization process in a fluid-bed rotor granulator using
      experimental design.
AB  - This study examined the effect of rotor speed, amount of water sprayed, and
      atomizing air pressure on the geometric mean diameter and geometric standard
      deviation of pellets produced in a fluid-bed rotor granulator using a 23
      factorial design and an optimization technique. Pellets were prepared by wet
      granulation. Equal amounts of microcrystalline cellulose, alpha-lactose
      monohydrate, and distilled water were used as the granulation liquid. The size
      and the size distribution of the pellets were determined by sieve analysis. The
      size of the pellets was found to be dependent on the amount of water added, while
      an increase in rotor speed decreased their size. Both factors were found to be
      statistically significant (P <.05). The effect of atomizing air pressure on
      pellet size was not statistically significant. None of the 3 factors
      significantly affected the geometric standard deviation of the pellets. The rotor
      speed and the amount of water sprayed were further selected in order to construct
      a mathematical model that correlates these factors with the geometric mean
      diameter of the pellets. For this purpose, the optimization technique 3(2) was
      used. The derived equation described the relationship between the selected
      factors and the size of the pellets. As a result, the experimental design
      techniques applied were found to be suitable in optimizing the pelletization
      process carried out in a fluid-bed rotor granulator.

PMID- 14727901
TI  - Competitive inhibitory effect of external nucleophile concentration on
      intramolecular O- to N-acylation in O-acetylsalicylamide.

PMID- 14727902
TI  - Dry blending process scale-up for a very low dose drug candidate.

PMID- 14727903
TI  - Structural analysis of microparticles by confocal laser scanning microscopy.
AB  - This study demonstrates the potential of confocal laser scanning microscopy
      (CLSM) as a characterization tool for different types of microparticles.
      Microparticles were prepared by various methods including complex coacervation,
      spray drying, double emulsion solvent evaporation technique, and ionotropic
      gelation. Protein drugs and particle wall polymers were covalently labeled with a
      fluorescent marker prior to particle preparation, while low molecular weight
      drugs were labeled by mixing with a fluorescent marker of similar solubility
      properties. As was demonstrated in several examples, CLSM allowed visualization
      of the polymeric particle wall composition and detection of heterogeneous polymer
      distribution or changes in polymer matrix composition under the influence of the
      drug. Furthermore, CLSM provides a method for three-dimensional reconstruction
      and image analysis of the microparticles by imaging several coplanar sections
      throughout the object. In conclusion, CLSM allows the inspection of internal
      particle structures without prior sample destruction. It can be used to localize
      the encapsulated compounds and to detect special structural details of the
      particle wall composition.

PMID- 14727904
TI  - Composite method to quantify powder flow as a screening method in early tablet or
      capsule formulation development.
AB  - The flow properties of typical tablet and capsule formulation excipients, active
      compounds, and representative formulation blends were tested with current and
      novel flow measurement techniques to identify a reliable bench test to quantify
      powder flow as a screening method in early tablet and capsule formulation
      development. Test methods employed were vibrating spatula, critical orifice,
      angle of repose, compressibility index, and avalanching analysis. Powder flow
      results from each method were compiled in a database, sorted, and compared. An
      empirical composite index was established and powder flow was ranked in
      accordance with formulator experience. Principal components analyses of the angle
      of repose, percent compressibility, and critical orifice of the powder materials
      were also performed. The first principal component accounted for 72.8% of data
      variability; scores associated with this principal component score can serve as
      an index of flowability. Data generated from vibrating spatula and avalanching
      methods were not reproducible and were inconsistent with formulator experience
      and cited vendor references for flow. Improvements of test instruments and
      further studies are necessary for better assessment of these approaches.

PMID- 14727905
TI  - Evaluation of alginate compressed matrices as prolonged drug delivery systems.
AB  - This research investigated the use of sodium alginate for the preparation of
      hydrophylic matrix tablets intended for prolonged drug release using ketoprofen
      as a model drug. The matrix tablets were prepared by direct compression using
      sodium alginate, calcium gluconate, and hydroxypropylmethylcellulose (HPMC) in
      different combinations and ratios. In vitro release tests and erosion studies of
      the matrix tablets were carried out in USP phosphate buffer (pH 7.4). Matrices
      consisting of sodium alginate alone or in combination with 10% and 20% of HPMC
      give a prolonged drug release at a fairly constant rate. Incorporation of
      different ratios of calcium gluconate leads to an enhancement of the release rate
      from the matrices and to the loss of the constant release rate of the drug. Only
      the matrices containing the highest quantity of HPMC (20%) maintained their
      capacity to release ketoprofen for a prolonged time.

PMID- 14727906
TI  - Evaluation of quick disintegrating calcium carbonate tablets.
AB  - The purpose of this investigation was to develop a rapidly disintegrating calcium
      carbonate (CC) tablet by direct compression and compare it with commercially
      available calcium tablets. CC tablets were formulated on a Carver press using 3
      different forms of CC direct compressed granules (Cal-Carb 4450, Cal-Carb 4457,
      and Cal-Carb 4462). The breaking strength was measured using a Stokes-Monsanto
      hardness tester. The disintegration and dissolution properties of the tablets
      were studied using USP methodology. The calcium concentration was determined by
      an atomic absorption spectrophotometer. Scanning electron microscopy was used to
      evaluate the surface topography of the granules and tablets. Breaking strength of
      Cal-Carb 4450, Cal-Carb 4457, and Cal-Carb 4462 tablets was in the range of 7.2
      to 7.7 kg, as compared with a hardness of 6.2 kg and 10 kg for the commercially
      available calcium tablets Citracal and Tums, respectively. The disintegration
      time for the tablets presented in the order earlier was 4.1, 2.1, 1.9, 2.9, and
      9.7 minutes, respectively. The dissolution studies showed that all formulations
      released 100% of the elemental calcium in simulated gastric fluid in less than 20
      minutes. In summary, this study clearly demonstrated that quick disintegrating CC
      tablets can be formulated without expensive effervescence technology.

PMID- 14727907
TI  - Development of a dual approach to assess powder flow from avalanching behavior.
AB  - The purposes of this investigation were to develop a method to evaluate flow
      properties of powders from avalanching tests and to detect similarities and
      relationships between these data and conventional powder flow properties. The API
      AeroFlow automated flowability analyzer was tested using 6 pharmaceutical
      excipients. Data were presented as mean time to avalanche (MTA), scatter, and a
      classification based on the type of motion of the powder bed. Powders were also
      characterized in terms of particle size, particle shape, loss of weight on
      drying, Carr's compressibility index, and critical orifice diameter to prevent
      ratholing. A dual approach, which combines visual observation of the type of
      motion of the powder bed in the rotating drum with numerical descriptors such as
      MTA and scatter, was found to be more accurate in the assessment of powder flow
      than the current practice of using only MTA and scatter values. Statistical
      analysis established that there are relationships and similarities between the
      ranking of powder flow properties obtained from the avalanching test and Carr's
      compressibility index and the critical orifice diameter. An interaction between
      particle size and shape, both influencing powder flow, when evaluated with these
      methods was found. The assessment of the flowability of powders on the basis of
      avalanching tests should include both the determination of numerical descriptors
      of flow such as MTA and scatter, and a determination of the type of motion of the
      powder bed in order to increase the sensitivity of the method to small changes in
      powder flow properties.

PMID- 14727908
TI  - The potential of organic-based amylose-ethylcellulose film coatings as oral colon
      specific drug delivery systems.
AB  - Amylose-ethylcellulose film coatings obtained from organic-based solvents were
      investigated as potential vehicles for colonic drug delivery. Amylose, in the
      form of an amylose-butan-1-ol dispersion, and ethylcellulose, dissolved in either
      ethyl lactate, ethanol, or propanol and plasticized with dibutyl sebacate, were
      mixed in various proportions and applied using a fluidized bed coater to achieve
      a range of film thicknesses on 5-aminosalicylic acid pellets. Drug release from
      the coated pellets was assessed under gastric and small intestinal conditions in
      the presence and absence of pepsin and pancreatin using dissolution methodology,
      and also within a simulated colonic environment involving fermentation testing
      with human feces in the form of a slurry. Under upper gastrointestinal tract
      conditions, the rate and extent of drug release were found to be related to the
      thickness of the coating and the ratio of amylose to ethylcellulose within the
      film. Modeling of the drug release data revealed that the ratio was more
      important than coat thickness in controlling drug release, irrespective of the
      solvent used for coating. Coatings with a thick film and/or low amylose content
      were relatively impermeable and able to delay drug release under conditions
      mimicking the upper gastrointestinal tract. Furthermore, drug release was
      unaffected by the presence of pepsin and pancreatin and by long-term storage.
      Under simulated colonic conditions, drug release was more pronounced from coating
      formulations containing higher proportions of amylose. Colon-specificity can
      therefore be achieved using such systems by judicious choice of the appropriate
      ratio of amylose to ethylcellulose and coat thickness.

PMID- 14727909
TI  - Thermal behavior of a pharmaceutical solid acetaminophen doped with p
      aminophenol.
AB  - Thermal behavior of a series of acetaminophen (APAP) doped with p-aminophenol
      (PANP) was studied by differential scanning calorimetry (DSC) to determine
      whether it exhibited a eutectic system. Within the temperature range of 120 to
      200 degrees C, accurately weighed (1-2 mg) samples sealed in hermetic pans were
      calorimetrically scanned with a low scanning rate of 1 degrees C/min. The mixture
      formed a single eutectic with the composition ratio APAP/PANP of 0.6/0.4 at a
      temperature of 138 degrees C, where it liquefied. Melting began as early as at
      the eutectic point, which was below the melting temperature of APAP (169 degrees
      C). The melting point as well as heat of APAP fusion was depressed with the
      increase in doped PANP. It was postulated that there might be a deficit heat of
      APAP fusion in APAP doped with PANP, which was coincident with the heat consumed
      by early liquefaction. The deficit heat was used to correct fraction molten in
      the van't Hoff law of purity determination. It was found that the purity
      determination of APAP doped with PANP was comparable to the UV-spectroscopic
      method up to the maximum doped PANP level of 8 mol percent. It was concluded that
      DSC was able to approach early heat of liquefaction of APAP doped with PANP. The
      van't Hoff law may be applicable to the determination of APAP with the presence
      of PANP as a eutectic impurity.

PMID- 14727910
TI  - Effect of Carbopol and polyvinylpyrrolidone on the mechanical, rheological, and
      release properties of bioadhesive polyethylene glycol gels.
AB  - This study examined the mechanical (hardness, compressibility, adhesiveness, and
      cohesiveness) and rheological (zero-rate viscosity and thixotropy) properties of
      polyethylene glycol (PEG) gels that contain different ratios of Carbopol 934P
      (CP) and polyvinylpyrrolidone K90 (PVP). Mechanical properties were examined
      using a texture analyzer (TA-XT2), and rheological properties were examined using
      a rheometer (Rheomat 115A). In addition, lidocaine release from gels was
      evaluated using a release apparatus simulating the buccal condition. The results
      indicated that an increase in CP concentration significantly increased gel
      compressibility, hardness, and adhesiveness, factors that affect ease of gel
      removal from container, ease of gel application onto mucosal membrane, and gel
      bioadhesion. However, CP concentration was negatively correlated with gel
      cohesiveness, a factor representing structural reformation. In contrast, PVP
      concentration was negatively correlated with gel hardness and compressibility,
      but positively correlated with gel cohesiveness. All PEG gels exhibited
      pseudoplastic flow with thixotropy, indicating a general loss of consistency with
      increased shearing stress. Drug release T50% was affected by the flow rate of the
      simulated saliva solution. A reduction in the flow rate caused a slower drug
      release and hence a higher T50% value. In addition, drug release was
      significantly reduced as the concentrations of CP and PVP increased because of
      the increase in zero-rate viscosity of the gels. Response surfaces and contour
      plots of the dependent variables further substantiated that various combinations
      of CP and PVP in the PEG gels offered a wide range of mechanical, rheological,
      and drug-release characteristics. A combination of CP and PVP with complementary
      physical properties resulted in a prolonged buccal drug delivery.

PMID- 14727911
TI  - Prediction of adsorption from multicomponent solutions by activated carbon using
      single-solute parameters.
AB  - The adsorption of 3 barbiturates--phenobarbital, mephobarbital, and primidone-
      from simulated intestinal fluid (SIF), without pancreatin, by activated carbon
      was studied using the rotating bottle method. The concentrations of each drug
      remaining in solution at equilibrium were determined with the aid of a high
      performance liquid chromatography (HPLC) system employing a reversed-phase
      column. The competitive Langmuir-like model, the modified competitive Langmuir
      like model, and the LeVan-Vermeulen model were each fit to the data. Excellent
      agreement was obtained between the experimental and predicted data using the
      modified competitive Langmuir-like model and the LeVan-Vermeulen model. The
      agreement obtained from the original competitive Langmuir-like model was less
      satisfactory. These observations are not surprising because the competitive
      Langmuir-like model assumes that the capacities of the adsorbates are equal,
      while the other 2 models take into account the differences in the capacities of
      the components. The results of these studies indicate that the adsorbates
      employed are competing for the same binding sites on the activated carbon
      surface. The results also demonstrate that it is possible to accurately predict
      multicomponent adsorption isotherms using only single-solute isotherm parameters.
      Such prediction is likely to be useful for improving in vivo/in vitro
      correlations.

PMID- 14727912
TI  - Effect of drying methods on retention of moist sucralfate gel properties.
AB  - The aim of this work was to find a drying procedure for moist sucralfate gel
      capable of producing dried sucralfate gel that retains the original gel
      properties of bioadhesion, rheology, and micromeritics. Spray-drying and
      microwave-drying procedures were employed. Mannitol was used as a gel-protective
      substance during the drying processes. The spray drying of moist sucralfate gel
      gave rise to a powder whose water suspensions showed significantly reduced
      viscosity. The bioadhesion of spray-dried sucralfate gel was strongly reduced by
      drying. When mannitol was used as a gel protector, the spray-dried sucralfate in
      part maintained the original bioadhesion of moist sucralfate gel. The preparation
      of a dried sucralfate gel retaining the bioadhesion characteristics, avoiding the
      use of mannitol, was made possible using the microwave-drying procedure. The
      microwave-dried product possesses a granular morphology suitable for direct
      compression because it is a free flowing and strongly coherent granular powder.

PMID- 14727913
TI  - Genomics and proteomics.

PMID- 14727914
TI  - Drug-protein adducts: an industry perspective on minimizing the potential for
      drug bioactivation in drug discovery and development.
AB  - It is generally accepted that there is neither a well-defined nor a consistent
      link between the formation of drug-protein adducts and organ toxicity. Because
      the potential does exist, however, for these processes to be causally related,
      the general strategy at Merck Research Laboratories has been to minimize reactive
      metabolite formation to the extent possible by appropriate structural
      modification during the lead optimization stage. This requires a flexible
      approach to defining bioactivation issues in a variety of metabolism vectors and
      typically involves the initial use of small molecule trapping agents to define
      the potential for bioactivation. At some point, however, there is a requirement
      to synthesize a radiolabeled tracer and to undertake covalent binding studies in
      vitro, usually in liver microsomal (and sometimes hepatocyte) preparations from
      preclinical species and human, and also in vivo, typically in the rat. This paper
      serves to provide one pragmatic approach to addressing the issue of bioactivation
      from an industry viewpoint based on protocols adopted by Merck Research
      Laboratories. The availability of a dedicated Labeled Compound Synthesis group,
      coupled to a close working relationship between Drug Metabolism and Medicinal
      Chemistry, represents a framework within which this perspective becomes viable;
      the overall aim is to bring safer drugs to patients.

PMID- 14727915
TI  - The cyclopentenone product of lipid peroxidation, 15-A2t-isoprostane, is
      efficiently metabolized by HepG2 cells via conjugation with glutathione.
AB  - Cyclopentenone isoprostanes (IsoPs), A(2)/J(2)-IsoPs, are one class of IsoPs
      formed via the free radical-initiated peroxidation of arachidonic acid. These
      compounds, which are structurally similar to cyclooxygenase-derived PGA(2) and
      PGJ(2), contain highly reactive alpha,beta-unsaturated carbonyl moieties.
      A(2)/J(2)-IsoPs are generated in vivo in humans esterified in
      glycerophospholipids. Unlike other classes of IsoPs, however, cyclopentenone
      IsoPs cannot be detected in the free form; we postulated that this might be due
      to their rapid adduction to various thiol-containing biomolecules via Michael
      addition. Recently, we reported that the A-ring IsoP, 15-A(2t)-IsoP, is
      efficiently conjugated with glutathione in vitro by certain human and rat
      glutathione transferases (GSTs), with the isozyme GSTA4-4 displaying the highest
      activity. Herein, we examined the metabolic disposition of 15-A(2t)-IsoP in HepG2
      cells. We report that 15-A(2t)-IsoP is primarily metabolized by these cells via
      conjugation to glutathione. Within 6 h, approximately 60% of 15-A(2t)-IsoP added
      to HepG2 cells was present in the form of a water soluble conjugate(s).
      Structural characterization of the adduct(s) by liquid chromatography-tandem mass
      spectrometry revealed four major conjugates. These include the intact 15-A(2t)
      IsoP-GSH conjugate, the GSH conjugate in which the carbonyl at C-9 of 15-A(2t)
      IsoP is reduced, and the corresponding cysteine conjugates. These studies thus
      show that the primary pathway of metabolic disposition of endogenously derived
      cyclopentenone IsoPs occurs via conjugation with thiols.

PMID- 14727916
TI  - A planar catechin analogue having a more negative oxidation potential than (+)
      catechin as an electron transfer antioxidant against a peroxyl radical.
AB  - The hydrogen transfer reaction of antioxidative polyphenol with reactive oxygen
      species has proved to be the main mechanism for radical scavenging. The planar
      catechin (P1H(2)), in which the catechol and chroman structure in (+)-catechin
      (1H(2)) are constrained to be planar, undergoes efficient hydrogen atom transfer
      toward galvinoxyol radical, showing an enhanced protective effect against the
      oxidative DNA damage induced by the Fenton reaction. The present studies were
      undertaken to further characterize the radical scavenging ability of P1H(2) in
      the reaction with cumylperoxyl radical, which is a model radical of lipid peroxyl
      radical for lipid peroxidation. The kinetics of hydrogen transfer from catechins
      to cumylperoxyl radical has been examined in propionitrile at low temperature
      with use of ESR, showing that the rate of hydrogen transfer from P1H(2) is
      significantly faster than that from 1H(2). The rate was also accelerated by the
      presence of Sc(OSO(2)CF(3))(3). Such an acceleration effect of metal ion
      indicates that the hydrogen transfer reaction proceeds via metal ion-promoted
      electron transfer from P1H(2) to oxyl radical followed by proton transfer rather
      than via a one-step hydrogen atom transfer. The electrochemical ease of P1H(2)
      for the one-electron oxidation investigated by second-harmonic alternating
      current voltammetry strongly supports the two step mechanism for hydrogen
      transfer, resulting in the enhanced radical scavenging ability.

PMID- 14727917
TI  - Peroxynitrite delivery methods for toxicity studies.
AB  - The endogenous synthesis of peroxynitrite (ONOO(-)) has been implicated in a
      number of diseases, but assessments of its cytotoxicity and genotoxicity have
      been hampered by its extremely short half-life under physiological conditions
      (<20 ms) and the consequent difficulty in exposing cells to known concentrations
      of it over at least several hours. Two methods for peroxynitrite delivery to cell
      cultures were investigated, one involving steady infusion of preformed ONOO(-)
      and the other based on the continuous in situ synthesis of ONOO(-) from NO and
      O(2)(-). In the latter, NO was supplied by diffusion through gas permeable tubing
      and O(2)(-) was generated using the hypoxanthine-xanthine oxidase reaction. The
      performance of both methods was assessed by measuring the rates of formation of
      tyrosine derivatives (dityrosine and nitrotyrosine) that are commonly employed as
      biomarkers for peroxynitrite. Experimental results in the absence of cells were
      compared in each case with predictions from kinetic models. In the infusion
      system, the measured dityrosine and nitrotyrosine yields were in excellent
      agreement with those predicted from the model. To characterize the other system,
      experiments were performed first to determine the kinetics of hypoxanthine
      oxidation by xanthine oxidase and uric acid oxidation by uricase. Simulations of
      the complex reaction network in the complete synthesis system suggested that
      dityrosine should be the major product there, that the yields of both tyrosine
      derivatives should be very sensitive to the relative rates of NO and O(2)(-)
      delivery, and that equal rates for NO and O(2)(-) should maximize those yields.
      Experiments performed under the predicted optimal conditions showed much lower
      levels of dityrosine than expected and no detectable nitrotyrosine. The
      unexpectedly low yields of tyrosine products could be explained largely by the
      partial inactivation of both xanthine oxidase and uricase by peroxynitrite
      derived NO(2) and CO(3)(-) radicals. We conclude that continuous infusion of
      peroxynitrite is the more promising approach.

PMID- 14727918
TI  - Formation and mass spectrometric analysis of DNA and nucleoside adducts by S-(1
      acetoxymethyl)glutathione and by glutathione S-transferase-mediated activation of
      dihalomethanes.
AB  - The dihalomethane CH(2)Cl(2) is an industrial solvent of potential concern to
      humans because of its potential genotoxicity and carcinogenicity. To characterize
      DNA damage by dihalomethanes, a rapid DNA digestion under acidic conditions was
      developed to identify alkali labile DNA-dihalomethane nucleoside adducts using
      HPLC-electrospray mass spectrometry. DNA digestion worked best using pH 5.0
      sodium acetate buffer, a 30 min incubation with DNase II and phosphodiesterase
      II, and a 2 h acid phosphatase digest. DNA was modified with S-(1
      acetoxymethyl)glutathione (GSCH(2)OAc), a reagent modeling activated
      dihalomethanes. Adducts to G, A, and T were detected at high ratios of
      GSCH(2)OAc/DNA following digestion of the DNA with the procedure used here. The
      relative efficacy of adduct formation was G > T > A >> C. The four DNA
      nucleosides were also reacted with the dihalomethanes CH(2)Cl(2) and CH(2)Br(2)
      in the presence of glutathione (GSH) and GSH S-transferases from bacteria (DM11),
      rat (GST 5-5), and human (GST T1-1) under conditions that produce mutations in
      bacteria. All enzymes formed adducts to all four nucleosides, with dGuo being the
      most readily modified nucleoside. Thus, the pattern paralleled the results
      obtained with the model compounds GSCH(2)OAc and DNA. CH(2)Cl(2) and CH(2)Br(2)
      yielded similar amounts of adducts under these conditions. The relative
      efficiency of adduct formation by GSH transferases was rat 5-5 > human T1-1 >
      bacterial DM11, showing that human GSH transferase T1-1 can form dihalomethane
      adducts under the conditions used. Although the lability of DNA adducts has
      precluded more sophisticated experiments and in vivo studies have not yet been
      possible, the work collectively demonstrates the ability of several GSH
      transferases to generate DNA adducts from dihalomethanes, with G being the
      preferred site of adduction in both this and the GSCH(2)OAc model system.

PMID- 14727919
TI  - Cytotoxic action of juglone and plumbagin: a mechanistic study using HaCaT
      keratinocytes.
AB  - Juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (5-hydroxy-3-methyl-1,4
      naphthoquinone) are yellow pigments found in black walnut (Juglans regia). Herbal
      preparations derived from black walnut have been used as hair dyes and skin
      colorants in addition to being applied topically for the treatment of acne,
      inflammatory diseases, ringworm, and fungal, bacterial, or viral infections. We
      have studied the cytotoxicity of these quinones to HaCaT keratinocytes. Exposure
      to juglone or plumbagin (1-20 microM) resulted in a concentration-dependent
      decrease in cell viability. The cytotoxicity of these quinones is due to two
      different mechanisms, namely, redox cycling and reaction with glutathione (GSH).
      Redox cycling results in the generation of the corresponding semiquinone
      radicals, which were detected by electron paramagnetic resonance. Incubation of
      keratinocytes with the quinones generated hydrogen peroxide (H(2)O(2)) and
      resulted in the oxidation of GSH to GSSG. Depletion of GSH by buthionine
      sulfoximine enhanced semiquinone radical production, increased H(2)O(2)
      generation, and produced greater cytotoxicity, suggesting that GSH plays an
      important protective role. Both quinones decreased the intracellular levels of
      GSH. However, plumbagin stoichiometrically converted GSH to GSSG, indicating that
      redox cycling is its main metabolic pathway. In contrast, much of the GSH lost
      during juglone exposure, especially at the higher concentrations (10 and 20
      microM), did not appear as GSSG, suggesting that the cytotoxicity of this quinone
      may also involve nucleophilic addition to GSH. Our findings indicate that topical
      preparations containing juglone and plumbagin should be used with care as their
      use may damage the skin. However, it is probable that the antifungal, antiviral,
      and antibacterial properties of these quinones are the result of redox cycling.

PMID- 14727920
TI  - Environmental fine particulate matter (PM 2.5) activates the RAW 264.7 macrophage
      cell line even at very low concentrations as revealed by 1H NMR.
AB  - Because of the association between inhalation of airborne particulate matter (PM)
      and human respiratory and cardiovascular disease, it is necessary to understand
      the tissue damage induced by these particles. One of the cell types principally
      involved in the body's reaction to PM are macrophages, which remove particles in
      the airway passages and the lungs through phagocytosis. In fact, when macrophages
      are exposed to a toxic agent such as PM, they undergo a series of changes
      (including variations in morphology, an increase in glycolysis, and consequent
      lactate production and the release of cytokines such as interleukin-6 and tumor
      necrosis factor-alpha) necessary to transform them from "resting" to "activated"
      macrophages. Because (1)H NMR is extremely useful in monitoring, noninvasively,
      macrophage metabolism and because this technique has never been utilized to
      examine macrophage activation after exposure to PM, it was the purpose of the
      present study to investigate the effects of PM exposure on the RAW 264.7
      stabilized macrophage cell line using (1)H NMR spectroscopy. PM with a diameter
      <2.5 microm (PM 2.5) was utilized because a closer association to mortality and
      adverse respiratory health effects has been found with this fraction than with
      particles of a larger size. Measurements were conducted on whole cells at both
      500 and 700 MHz as well as on perchloric acid extracts at 700 MHz. Significant
      variations in numerous metabolites were seen at very low concentrations of PM
      2.5. Many of these changes point to activation of RAW 264.7 macrophages even at
      doses of PM 2.5 much lower than those commonly employed in cell studies. These
      results are particularly significant since the same concentrations of PM did not
      induce changes in morphology and release of cytokines in these cells. Therefore,
      (1)H NMR spectroscopy is an extremely sensitive probe in observing subtle
      variations in macrophages after exposure to PM 2.5.

PMID- 14727921
TI  - In vitro reactivity of carboxylic acid-CoA thioesters with glutathione.
AB  - The chemical reactivity of acyl-CoA thioesters toward nucleophiles has been
      demonstrated in several recent studies. Thus, intracellularly formed acyl-CoAs of
      xenobiotic carboxylic acids may react covalently with endogenous proteins and
      potentially lead to adverse effects. The purpose of this study was to investigate
      whether a correlation could be found between the structure of acyl-CoA thioesters
      and their reactivities toward the tripeptide, glutathione (gamma-Glu-Cys-Gly).
      The acyl-CoA thioesters of eight carboxylic acids (ibuprofen, clofibric acid,
      indomethacin, fenbufen, tolmetin, salicylic acid, 2-phenoxypropionic acid, and (4
      chloro-2-methyl-phenoxy)acetic acid (MCPA)) were synthesized, and each acyl-CoA
      (0.5 mM) was incubated with glutathione (5.0 mM) in 0.1 M potassium phosphate (pH
      7.4, 37 degrees C). All of the acyl-CoAs reacted with glutathione to form the
      respective acyl-S-glutathione products, with MCPA-CoA having the highest rate of
      conjugate formation (120 +/- 10 microM/min) and ibuprofen-CoA having the lowest
      (1.0 +/- 0.1 microM/min). The relative reactivities of the acyl-CoAs were
      dependent on the substitution at the carbon atom alpha to the acyl carbon and on
      the presence of an oxygen atom in a position beta to the acyl carbon and were as
      follows: phenoxyacetic acid > o-hydroxybenzoic acid--phenoxypropionic acid >
      arylacetic acid derivatives > 2-methyl-2-phenoxypropionic acid--2-phenylpropionic
      acid. For each acyl-CoA thioester, the overall hydrolysis rate was determined as
      the time-dependent formation of parent compound. A linear trend was observed when
      comparing the reactivities of the acyl-CoAs with glutathione with the
      corresponding overall hydrolysis rates. Thus, the most reactive compound (MCPA
      CoA) was also the compound with the highest rate of hydrolysis and the least
      reactive compounds (ibuprofen-CoA, clofibryl-CoA) were also the compounds least
      susceptible to hydrolysis.

PMID- 14727922
TI  - Tolerance induced by low dose D-penicillamine in the brown Norway rat model of
      drug-induced autoimmunity is immune-mediated.
AB  - Most patients taking drugs associated with idiosyncratic drug reactions tolerate
      the drug and do not develop adverse reactions. Understanding the mechanism of
      tolerance to drugs is important as it could provide insight into why some
      patients develop idiosyncratic reactions and others do not. The Brown Norway rat
      model of D-penicillamine-induced autoimmunity was used as a model of
      idiosyncratic drug-induced autoimmunity. Two weeks of low dose (5 mg/day) D
      penicillamine pretreatment completely prevented all clinical signs of
      autoimmunity normally seen in 60-80% of rats treated with high dose (20 mg/day) D
      penicillamine. Low dose pretreatment also prevented the increase in IgE and IL-4
      mRNA characteristic of the response to high dose D-penicillamine. Experiments
      were conducted to determine whether low dose tolerance is metabolic or
      immunological. It was found that low dose tolerance possesses key characteristics
      of immune-mediated tolerance: memory, splenocytes that adoptively transfer
      tolerance, and regulatory cytokine production. To provide an understanding of the
      factors that can prevent or reverse established tolerance, the conditions for
      inducing and maintaining tolerance were investigated. Tolerance induction was
      investigated by manipulating the immune system during the period of low dose
      exposure. The induction of tolerance was partially prevented by depleting the
      macrophage subset of antigen presenting cells with clodronate-filled liposomes or
      by inhibiting T cells with tacrolimus during the period of low dose exposure. As
      well, the induction of tolerance was completely prevented by repeatedly
      stimulating the immune system throughout the period of low dose pretreatment with
      poly I:C. To investigate the permanence of tolerance, the immune system was
      stimulated after tolerance induction in an attempt to break tolerance. Both LPS
      and poly I:C reversed tolerance in a dose-dependent manner. These results
      demonstrate that immune tolerance to D-penicillamine autoimmunity can be induced
      by short-term low dose pretreatment.

PMID- 14727923
TI  - Arsenic speciation in urine from acute promyelocytic leukemia patients undergoing
      arsenic trioxide treatment.
AB  - Arsenic has been used successfully in clinical trials for treating acute
      promyelocytic leukemia (APL). Although sublethal doses of inorganic arsenic are
      used, little is known about the pharmacokinetics and metabolism of the high
      levels of arsenic in APL patients. To fill this important gap, this study
      describes the speciation of arsenic in urine from four APL patients treated with
      arsenic. Each patient was injected daily with an arsenite (As(III)) solution that
      contained 10 mg of As(2)O(3) precursor. Speciation analysis of the patient urine
      samples collected consecutively for 48 h, encompassing two intravenous injections
      of arsenic, revealed the presence of monomethylarsonous acid (MMA(III)),
      dimethylarsinous acid (DMA(III)), monomethylarsonic acid (MMA(V)), and
      dimethylarsinic acid (DMA(V)). The intermediate methyl arsenic metabolites,
      MMA(III) and DMA(III), were detected in most urine samples from all of the
      patients when a preservative, diethyldithiocarbomate, was added to the urine
      samples to stabilize these trivalent arsenic species. The major arsenic species
      detected in the urine samples from the patients were As(III), MMA(V), and DMA(V),
      accounting for >95% of the total arsenic excreted. The relative proportions of
      As(III), As(V), MMA(V), and DMA(V) in urine samples collected 24 h after the
      injections of As(III) were 27.6 +/- 6.1, 2.8 +/- 2.0, 22.8 +/- 8.1, and 43.7 +/-
      13.3%, respectively. The relatively lower fraction of the methylated arsenic
      species in these APL patients under arsenic treatment as compared with that from
      the general population exposed to much lower levels of arsenic suggests that the
      high levels of As(III) inhibit the methylation of arsenic (inhibits the formation
      of methyl arsenic metabolites). The arsenic species excreted into the urine
      accounted for 32-65% of the total arsenic injected. These results suggest that
      other pathways of excretion, such as through the bile, may play an important role
      in eliminating (removing) arsenic from the human body when challenged by high
      levels of As(III).

PMID- 14727924
TI  - A novel approach based on solid phase microextraction gas chromatography and mass
      spectrometry to the determination of highly reactive organic compounds in cells
      cultures: styrene oxide.
AB  - A solid phase microextraction (SPME) gas chromatography/mass spectrometry (GC/MS)
      method was developed to assess actual doses of highly reactive organic compounds
      like styrene oxide (SO) in exposed cell cultures. Using SPME, we set up a method
      to measure accurately extracellular SO concentrations as well as to obtain an
      approximate assessment of intracellular levels. The SPME-GC/MS method was
      developed and validated using two different coating materials, carboxen-PDMS and
      polyacrylate. In cell-free systems, linearity was established over 3 orders of
      magnitude for both fibers, but carboxen-PDMS showed higher extraction efficiency
      and a lower limit of detection (0.5 x 10(-7) vs 10(-6) M for polyacrylate).
      Precision calculated as % RSD was within 4-16% for all intra- and interday
      determinations. Experiments performed to study SO stability in cell-free medium
      showed a time-dependent decrease in SO concentration (11% of initial the
      concentration after 24 h), mostly due to the spontaneous hydrolysis of SO into
      styrene glycol, which was measured by liquid chromatography/tandem mass
      spectrometry (LC/MS/MS). When the neuronal cell line (SK-N-MC) was exposed to a
      nominal concentration of 0.3 x 10(-4) M SO, the actual concentration measured in
      the supernatant was considerably lower and was found to decrease during
      incubation. Intracellular SO was estimated indirectly, by difference between the
      amount measured in the medium without cells and in the supernatant of the cell
      containing medium.

PMID- 14727925
TI  - Model studies on the metal-catalyzed protein oxidation: structure of a possible
      His-Lys cross-link.
AB  - Redox active transition metals such as copper and iron contribute to
      biomacromolecular damage that occurs during oxidative stress in a number of
      degenerative disorders and results in protein cross-linking. On the basis of
      suggestive evidence for an oxyradical-induced cross-linking between His and Lys
      side chains, we investigated the Cu(II)-catalyzed oxidation of 4-alkylimidazoles
      in the presence of amines, as surrogates for these amino acid side chains, using
      ascorbic acid as a continual source of reducing equivalents. A model His-Lys
      cross-link was isolated and structurally characterized as a 5-alkyl-5-hydroxy-4
      (alkylamino)-1,5-dihydroimidazol-2-one by NMR and mass spectrometry. Evidence
      that the 2-imidazolone, the principal oxidation product found in the absence of
      amine, is an intermediate in the formation of the imidazole-amine adduct was that
      higher yields of the cross-link adduct were obtained starting with the 2
      imidazolone. Possible mechanisms for formation of the cross-link and other
      observed products are discussed.

PMID- 14727926
TI  - Depolarization of mitochondria and activation of caspases are common features of
      arsenic(III)-induced apoptosis in myelogenic and lymphatic cell lines.
AB  - The clinical efficacy of arsenic(III) oxide (As(2)O(3)) has been shown in
      patients with relapsed acute promyelocytic leukemia (APL). To identify potential
      common primary targets of action of As(2)O(3) in myelogenic and lymphatic cell
      lines, we analyzed As(2)O(3) effects on caspases and on the mitochondrial
      membrane potential (Psi(M)) under uniform conditions. As(2)O(3) induced breakdown
      of Psi(M) and activated caspases in cell lines with different sensitivities for
      As(2)O(3), including cell lines resistant to mitoxantron or camptothecin but
      sensitive to As(2)O(3). Caspase inhibitors could not prevent breakdown of Psi(M)
      in lymphoid cell lines, whereas activation of caspases and apoptosis could be
      inhibited. Activation of caspases seems to be a downstream effect occurring after
      breakdown of Psi(M). We could show that all of these effects are independent of
      MDR-1 expression. There was no difference in the mode of action of As(2)O(3) in
      cell lines sensitive or resistant to camptothecin, mitoxantrone, or doxorubicin.
      As(2)O(3) deserves further evaluation as an adjunct or alternative to other
      cytostatic drugs.

PMID- 14727927
TI  - Effect of selective serotonin reuptake inhibitors on platelet activation: can
      they prevent acute myocardial infarction?
AB  - In recent years a large body of evidence from several longitudinal studies has
      emerged suggesting that depression is an independent risk factor for
      cardiovascular disease (CVD) and that the association between depression and
      increased CVD risk is not merely due to negative mood-driven behavior related
      with depression. Even though the underlying mechanisms are not well understood,
      several hypotheses and explanations have been proposed such as increased
      activation of the hypothalamic-pituitary-adrenal axis, abnormalities in the
      sympathoadrenal system, or abnormalities in platelet function. Platelet function
      abnormalities, including increased platelet reactivity, may predispose patients
      with depressive disorders to clotting diatheses and may explain their
      vulnerability to CVD. Serotonin secreted by platelets induces both platelet
      aggregation and coronary vasoconstriction. Even though serotonin itself is only a
      weak platelet agonist, it markedly enhances platelet reactions to a variety of
      other agonists. Several studies have shown that selective serotonin reuptake
      inhibitors (SSRIs) reduce platelet and whole blood serotonin concentrations after
      repeated doses, and could therefore exert an inhibitory effect on platelet
      activation. For that reason, it was hypothesized that SSRIs could have a
      protective effect against myocardial infarction (MI). Results from three
      currently available epidemiological studies assessing the risk of MI in patients
      treated with antidepressants, including SSRIs, are controversial with respect to
      a potential beneficial effect of SSRIs on CVD risk in depressed patients.
      However, there is evidence that exposure to SSRIs does not substantially increase
      the risk of CVD in patients. A recent randomized, double-blind, placebo
      controlled, multicenter trial that evaluated the safety and efficacy of the SSRI
      sertraline in patients with major depression and acute MI or unstable angina
      suggested that sertraline is well tolerated and effective. Further
      epidemiological studies or longer-term clinical trials may shed more light on
      this issue, and answer the question conclusively, whether the effect of SSRIs on
      platelets or another mechanism translates into a decreased risk of CVD in
      depressed patients.

PMID- 14727928
TI  - Risk of suicide in users of cardiovascular drugs: a review of the epidemiological
      evidence.
AB  - An association between consumption of cardiovascular drugs and increased risk of
      depression was first reported more than 30 years ago. More recently three
      observational studies have also reported an association between the use of
      cardiovascular drugs and risk of suicide. We review the epidemiological evidence
      with particular focus on bias, confounding, and chance as alternative
      explanations to a causal association. The results of the three studies are
      inconsistent with respect to the association between cardiovascular drug use and
      suicide. None of the studies has been able to control fully for possible
      confounding, in particular by the underlying disease and comorbidity. We thus
      conclude that the finding of an association between suicide risk and
      cardiovascular drug use remains dubious. A true explanation for the apparent
      increase in risk of suicide in users of cardiovascular drugs remains unknown.
      Future studies must try to reduce confounding. Meta-analyses of data from
      existing trials may be an approach to solve the problem of confounding.

PMID- 14727929
TI  - Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid
      derivative: a critical review of potential benefits and drawbacks.
AB  - It has been clearly shown that lowering low density lipoprotein-cholesterol (LDL
      C) [most often with an HMG-CoA reductase inhibitor] decreases the risk of a
      cardiovascular event. However, this risk reduction was, at most, 35% in clinical
      trials, meaning that many events could not be prevented. Moreover, reaching
      target lipid values as recommended by the current guidelines is often difficult,
      mainly in high-risk situations such as secondary prevention or type 2 diabetes
      mellitus. As the two main classes of lipid-lowering drugs (HMG-CoA reductase
      inhibitors and fibric acid derivatives) have complementary effects on lipid
      parameters, it seems logical to combine both treatments particularly in patients
      with combined hyperlipidemia. In fact, combination therapy with an HMG-CoA
      reductase inhibitor and a fibric acid derivative induces a further decrease in
      LDL-C levels compared with monotherapy and improves other lipid values such as
      high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) levels.
      Unfortunately, there are currently no available randomized, prospective clinical
      data on the reduction of the incidence of cardiovascular events with such a
      combination. This is mainly because the use of HMG-CoA reductase inhibitor and
      fibric acid derivative combinations was initially described as dangerous. It is
      true that such a combination increases the risk of muscle toxicity that already
      exists with monotherapy. Muscle toxicity can eventually lead to life-threatening
      rhabdomyolysis and some precautions of use are required; however, the risk seems
      actually lower than what has been initially reported. The use of combined therapy
      with an HMG-CoA reductase inhibitor and a fibric acid derivative requires the
      respect of some rules such as avoiding the prescription in patients with
      concomitant conditions like renal failure and avoiding the use of gemfibrozil as
      a fibric acid derivative in such a combination. It is now imperative to design
      clinical trials to determine the clinical efficacy and precise safety of this
      combined treatment especially in patients with abnormalities in every parameter
      of the lipid triad (LDL, HDL and TG) and a high vascular risk such as patients
      with type 2 diabetes mellitus.

PMID- 14727930
TI  - Cost effectiveness of HMG-CoA reductase inhibitors in the management of coronary
      artery disease: the problem of under-treatment.
AB  - HMG-CoA reductase inhibitors significantly reduce the risk of coronary artery
      disease (CAD) events and CAD-related mortality in patients with and without
      established CAD. Consequently, HMG-CoA reductase inhibitors have a central role
      within recommendations for lipid-modifying therapy. However, despite these
      guidelines, only one-third to one-half of eligible patients receive lipid
      lowering therapy and as few as one-third of these patients achieve recommended
      target serum levels of low density lipoprotein-cholesterol. The underuse of HMG
      CoA reductase inhibitors in eligible patients has important implications for
      mortality, morbidity and cost, given the enormous economic burden associated with
      CAD; direct healthcare costs, estimated at US $16-53 billion (2000 values) in the
      US and 1.6 billion pound (1996 values) in the UK alone, are largely driven by
      inpatient care. Hospitalization costs are reduced by treatment with HMG-CoA
      reductase inhibitors, particularly in high-risk groups such as patients with CAD
      and diabetes mellitus in whom net cost savings may be achieved. HMG-CoA reductase
      inhibitors are underused because of institutional factors and clinician and
      patient factors. Also, the vast number of patients eligible for treatment means
      that the use of HMG-CoA reductase inhibitors is undoubtedly limited by budgetary
      considerations. Secondary prevention in CAD using HMG-CoA reductase inhibitors is
      certainly cost effective. Primary prevention with HMG-CoA reductase inhibitors is
      also cost effective in many patients, depending upon CAD risk and drug dosage. As
      new, more powerful, HMG-CoA reductase inhibitors come to market, and the
      established HMG-CoA reductase inhibitors come off patent, the identification of
      the most cost-effective therapy becomes increasingly complex. Research in to the
      relative cost effectiveness of alternative HMG-CoA reductase inhibitors, taking
      full account of the institutional, clinician and patient barriers to uptake
      should be undertaken to identify the most appropriate role for the new therapies.

PMID- 14727931
TI  - Preventing renal dysfunction in patients with hypertension: clinical implications
      from the early AASK Trial results.
AB  - Strategies to delay progression of established renal disease have primarily been
      directed at examining the class of antihypertensive therapy and/or the level of
      blood pressure control. In diabetic renal disease many trials have noted a
      protective role of ACE inhibitor-based therapy over non-ACE inhibitor-based
      therapy. This paper reviews recent clinical trials evaluating hypertension
      related kidney disease including the interim results of the African-American
      Study of Kidney Diseases and Hypertension (AASK) Study, to date the largest
      prospective study of African-American patients with kidney disease due to
      hypertension. This trial reports a renoprotective effect of ACE inhibitor-based
      therapy over calcium-channel antagonist- based therapy. The renoprotective effect
      of ACE inhibitor-based therapy may, in part, be due to their antiproteinuric
      effect independent of blood pressure lowering.

PMID- 14727932
TI  - New anticoagulants: current status and future potential.
AB  - Arterial and venous thrombosis are a major cause of morbidity and mortality.
      Anticoagulants are a cornerstone of treatment in patients with these disorders.
      The two most frequently used anticoagulants, heparin and warfarin, have
      pharmacological and/or biophysical limitations that make them difficult to use in
      day-to-day clinical practice. Development of new anticoagulants, which were
      designed to overcome these limitations, has been facilitated by an increased
      understanding of the coagulation cascade, the advent of molecular modeling and
      structure-based drug design, and the realization that the treatment of thrombosis
      and its complications consumes billions of dollars in annual healthcare
      expenditures. New anticoagulants target various steps in the coagulation pathway.
      Coagulation is triggered by the factor VIIa/tissue factor complex and propagated
      by factors Xa and IXa, together with their activated cofactors, factor Va and
      VIIIa, respectively. Thrombin, the final effector in coagulation, then converts
      soluble fibrinogen into insoluble fibrin, the major matrix protein of the clot.
      New anticoagulation drugs that target each of these clotting enzymes have been
      developed. This review will focus on those drugs in more advanced stages of
      clinical evaluation. These include inhibitors of initiation of coagulation
      (tissue factor pathway inhibitor, nematode anticoagulant peptide and active-site
      blocked factor VIIa), inhibitors of propagation of coagulation (active-site
      blocked factor IXa, antibodies against factor IX/IXa, fondaparinux sodium, direct
      factor Xa inhibitors, protein C derivatives and soluble thrombomodulin), and
      thrombin inhibitors (hirudin, bivalirudin, argatroban and ximelagatran).

PMID- 14727933
TI  - The sirolimus-eluting stent: a review of its use in the treatment of coronary
      artery disease.
AB  - The sirolimus-eluting stent (CYPHER( trade mark )) is a metal stent coated with
      140 micro g/cm(2) of sirolimus blended with synthetic polymers. After stent
      implantation, sirolimus is slowly released causing localized cytostatic
      inhibition of proliferation of vascular smooth muscle cells in the peri-stent
      arterial wall over a period of about 1 month. Only minimal amounts of sirolimus
      enter the bloodstream and these appear to be insufficient to be of clinical
      relevance. In clinical trials that evaluated single de novo lesions and in-stent
      restenosis in patients with coronary artery disease, the sirolimus-eluting stent
      was associated with minimal neointimal hyperplasia. In four randomized trials in
      de novo lesions, sirolimus eluting stents produced a significantly lower
      incidence of major adverse cardiac events (MACE) than that observed in patients
      with uncoated stents, during periods of up to 2 years (p < 0.05 for all
      comparisons). The lower incidence of MACE was mostly due to a reduced requirement
      for repeat target vessel revascularization. At angiographic follow-up at periods
      of up to 8 months, late luminal loss was significantly smaller in the sirolimus
      eluting stent groups than in the uncoated-stent groups (p < 0.001 in all
      studies). The sirolimus-eluting stent was well tolerated in clinical trials of up
      to 3 years' follow-up. Because minimal blood levels of sirolimus are achieved,
      systemic adverse effects appear to be avoided. To date, there has been no
      evidence of any potential adverse effects resulting from the polymer coating or
      local drug toxicity. As yet, there is no evidence of an increased risk of
      subacute or late thrombosis, or aneurysm formation with the sirolimus-eluting
      stent compared with the uncoated stent. Long-term follow-up is needed to fully
      assess these theoretical concerns. Cost-effectiveness analyses over 12 months
      demonstrated a cost advantage for the sirolimus-eluting stent compared with an
      uncoated stent because of a reduced requirement for repeat target vessel
      revascularizations. CONCLUSION: Initial clinical trials with the sirolimus
      eluting stent in patients with de novo coronary lesions have shown a
      significantly reduced incidence of MACE and of restenosis compared with a
      standard stent. Efficacy appears to be maintained throughout follow-up periods of
      up to 2 years in randomized trials, and to date, systemic or local adverse
      effects have been avoided. If efficacy and tolerability are consistently
      demonstrated over the long term, the sirolimus-eluting stent will be a major
      advance in the control of in-stent restenosis.

PMID- 14727934
TI  - Transcription factor decoys for the prevention of vein bypass graft failure.
AB  - Failure of vein bypass grafts, performed for either coronary or lower extremity
      arterial occlusions, is a common clinical problem that incurs significant
      morbidity and mortality. Vein grafts provide a unique opportunity for genetic
      interventions, since the target tissue is available for manipulation ex vivo
      prior to implantation, and prior to the onset of the pathophysiologic events that
      lead to graft disease. Smooth muscle cell proliferation is a hallmark of
      neointimal hyperplasia in vein grafts and arteries, and is an attractive target
      for molecular therapy. Gene blockade strategies can be accomplished by delivery
      of small oligodeoxynucleotides (ODN) that target specific mRNAs ('antisense') or
      that competitively inhibit transcription factors ('decoys'). Transcription
      factors are attractive targets for molecular therapy since they influence the
      expression of a large number of genes involved in a coordinated cellular program.
      An ODN decoy approach has been developed targeting the transcription factor E2F,
      which is critically involved in cell cycle progression. Brief (10 minute)
      incubation of the ODN in solution, using non-distending pressure, results in
      efficient delivery of the ODN to >80% of cells in the vein wall. Preclinical
      studies in a rabbit model of vein grafting and hypercholesterolemia demonstrated
      a marked reduction in neointima formation, as well as prolonged resistance to
      graft atherosclerosis. Phase I/II studies conducted in lower extremity and
      coronary bypass patients have demonstrated safety and feasibility, and have also
      suggested possible efficacy. Large, randomized multicenter, phase III trials are
      currently under way to evaluate the efficacy of E2F decoy treatment on preventing
      vein bypass failure in both peripheral and coronary grafting procedures. These
      studies herald the arrival of a new class of molecular agents into the
      armamentarium of cardiovascular therapies.

PMID- 14727935
TI  - Therapeutic potential of platelet glycoprotein IIb/IIIa receptor antagonists in
      the management of ischemic stroke.
AB  - The only drug approved by the US FDA for use in patients with acute ischemic
      stroke is the thrombolytic, alteplase. Whereas alteplase rapidly restores blood
      flow, the drug has to be administered within 6 hours after symptom onset and is
      associated with an increased incidence of intracerebral hemorrhage (ICH).
      Moreover, transient and permanent re-occlusions associated with increased
      mortality continue to occur after thrombolysis with alteplase. Platelets are
      believed to play a pivotal role in the pathogenesis of atherothrombosis and the
      binding of the platelet glycoprotein (GP) IIb/IIIa receptor to fibrinogen is the
      final common pathway leading to platelet aggregation and thrombus formation.
      Antiplatelet agents such as platelet GP IIb/IIIa receptor antagonists have been
      studied in numerous multicenter, randomized clinical trials in patients with
      acute coronary symptoms (ACS). The intravenous GP IIb/IIIa receptor antagonists
      abciximab, eptifibatide and tirofiban are approved by the FDA for use in patients
      with ACS, and intravenous tirofiban is also approved for use during coronary
      intervention. Oral GP IIb/IIIa receptor antagonists such as lotrafiban,
      xemilofiban, sibrafiban and orbofiban have failed to provide myocardial
      protection in patients with ACS. Compared with ACS, few trials have evaluated the
      efficacy and tolerability of platelet GP IIb/IIIa receptor antagonists in
      patients with cerebrovascular syndromes. Agents such as SM-20302, TP201, ME3277,
      murine 7E3 F(ab')(2 )and SDZ-GPI 562 have been reported to preserve microvascular
      patency in different animal models of acute ischemic stroke and they may have
      neuroprotective properties. Platelet GP IIb/IIIa receptor antagonists may be
      suitable as a single therapeutic or as an adjunct therapeutic to thrombolysis
      with alteplase for the treatment of stroke. Platelet GP IIb/IIIa receptor
      antagonists may enhance the efficacy of thrombolytics and reduce potentially
      fatal adverse effects such as ICH. Preliminary results from the Abciximab in
      Emergent Stroke Treatment Trial (AbESTT) indicate that abciximab, administered as
      a bolus dose 0.25 mg/kg followed by 12-hour infusion, was associated with
      significant improvement in clinical rating scores and no significant increase in
      bleeding episodes in patients with acute stroke. The tolerability of argatroban
      in patients with acute stroke is currently being assessed in the multicenter
      Argatroban in Ischemic Stroke (ARGIS-1) trial.

PMID- 14727936
TI  - Atrial fibrillation in patients after cardiovascular surgery: incidence, risk
      factors, preventive and therapeutic strategies.
AB  - Atrial fibrillation in patients undergoing cardiovascular surgery is a common
      problem, occurring in 25-50% of patients. Older patients and those with a prior
      history of atrial fibrillation are at highest risk, as are those patients in whom
      preoperative treatment with beta-blockers has been discontinued. The immediate
      sequelae of this common complication include hemodynamic instability and
      congestive heart failure with long-term consequences including thromboembolic
      phenomena and increased cost and length of hospitalization. beta-Blockers,
      amiodarone, and sotalol have all been shown to decrease the incidence of
      postoperative atrial fibrillation, but their use may be limited by their adverse
      effects. Other agents have some promise as prophylactic agents, but need further
      verification. Biatrial pacing has been shown to be effective, especially when
      beta-blockers are used simultaneously. The goals for the treatment of atrial
      fibrillation include maintaining hemodynamic stability, controlling ventricular
      rate, preventing thromboembolic complications, and restoring sinus rhythm. The
      most effective strategy for the prevention of atrial fibrillation is to identify
      the highest-risk patients and target them for prophylaxis with beta-blockers,
      amiodarone, sotalol or pacing.

PMID- 14727937
TI  - The use of roxifiban (DMP754), a novel oral platelet glycoprotein IIb/IIIa
      receptor inhibitor, in patients with stable coronary artery disease.
AB  - INTRODUCTION: Intravenous platelet glycoprotein (GP) IIb/IIIa receptor inhibitors
      have a significant beneficial impact on the outcomes of patients undergoing high
      risk coronary interventions and in the stabilization of patients with unstable
      angina pectoris refractory to conventional medical treatment. The role of long
      term treatment with oral platelet GP IIb/IIIa receptor inhibitors in patients
      with coronary artery disease is unproven. This study examined the dose-response
      effect on inhibition of platelet aggregation by roxifiban (DMP754), a novel oral
      platelet GP IIb/IIIa receptor inhibitor, and its safety and tolerability in
      patients with a history of chronic stable angina pectoris. METHODS: Ninety-eight
      patients were randomized to receive either a placebo or 1 of 8 oral dosages of
      roxifiban. Twenty-two patients were enrolled in multiple-dose regimens, bringing
      the total study population to 120. The oral dosages were 0.25, 0.5, 0.75, 1,
      1.25, 1.5, 2, or 2.5 mg/day for up to 30 days. RESULTS: Pharmacodynamic response
      of roxifiban was clearly dose-dependent. Platelet aggregation inhibition in
      response to 10 micromol/L slope adenosine diphosphate was sustained throughout
      the study period (up to 1 month). No serious adverse events, including
      significant major bleeding events, were associated with roxifiban treatment.
      Minor bleeding was reported in 5% of participants in the placebo group (1 of 21
      cases) versus 26% in the study group (26 of 99 cases). Incidence of minor
      bleeding associated with roxifiban 2 and 2.5 mg/day was significantly (p < or =
      0.05) greater than that with placebo. Adverse events, including gastrointestinal
      disorders, platelet and clotting disorders, and urinary tract disorders, were
      observed in 1 of 21 cases (5%) in the placebo group and in 12 of 99 cases (12%)
      in the study group. Reversible thrombocytopenia without other complications
      developed in two patients. CONCLUSIONS: Roxifiban-induced inhibition of platelet
      aggregation was dose-dependent and sustained throughout the study period: higher
      drug dosages correlated with higher levels of platelet inhibition and higher
      incidence of minor bleeding events. No serious adverse events were observed at
      any dosage. Thus, roxifiban appears to be a potent oral platelet GP IIb/IIIa
      receptor inhibitor that is clinically well-tolerated and deserves further study
      as a new treatment strategy in patients with chronic stable angina pectoris.

PMID- 14727938
TI  - Spotlight on ramipril in the prevention of cardiovascular outcomes.
AB  - Ramipril (Altace)Use of tradenames is for product identification purposes only
      and does not imply endorsement.), an angiotensin-converting enzyme (ACE)
      inhibitor, is a prodrug which is rapidly hydrolyzed after absorption to the
      active metabolite ramiprilat. Earlier trials have shown that ACE inhibitors, when
      given to patients with low ejection fractions, have reduced the relative risk of
      myocardial infarction (MI) and other ischemic events by 14-23%. Subsequently, the
      double-blind, randomized, placebo-controlled, multicenter Heart Outcomes
      Prevention Evaluation (HOPE) study has shown that, in patients who are not known
      to have low ejection fraction or heart failure but are at increased risk for
      developing cardiovascular events, ramipril reduced the incidence of stroke, MI
      and death due to cardiovascular disease. Results from the HOPE study, in which
      9297 patients were randomized to receive either ramipril 10 mg/day or placebo for
      a mean of 4.5 years, indicate that ramipril reduced the relative risk of the
      composite outcome of MI, stroke and cardiovascular death by 22%. The incidence of
      the composite outcome was significantly lower in the ramipril group than in the
      placebo group (14.0% vs 17.8%). Patients who received ramipril, compared with
      placebo recipients, had a significantly decreased incidence of stroke, MI or
      death due to cardiovascular disease (3.4% vs 4.9%, 9.9% vs 12.3% and 6.1% vs
      8.1%, respectively). The relative risk of death from any cause was reduced among
      patients who received ramipril. In addition, treatment with ramipril reduced as
      the incidence of revascularization procedures, and, among patients with diabetes
      mellitus, ramipril reduced the incidence of complications related to diabetes
      mellitus, including the development of overt nephropathy. Moreover, in patients
      without a previous diagnosis of diabetes mellitus, ramipril, compared with
      placebo, significantly reduced the development of diabetes mellitus. Furthermore,
      compared with patients receiving placebo, patients receiving ramipril had a
      reduced rate of progression of carotid artery wall thickness. CONCLUSION:
      Ramipril 10 mg/day can significantly reduce the incidence of MI, stroke or death
      from cardiovascular causes in patients aged > or =55 years who are at increased
      risk for the development of ischemic cardiovascular events due to a history of
      stroke, coronary artery disease (with controlled blood pressure), diabetes
      mellitus plus at least one other risk factor or peripheral vascular disease but
      no heart failure or low ejection fraction. Therefore, in addition to dietary and
      lifestyle modifications, ramipril should be an integral part of secondary
      prevention therapy in patients at increased risk for the development of
      cardiovascular events.

PMID- 14727939
TI  - Cilostazol: a review of its use in intermittent claudication.
AB  - Cilostazol (Pletal) is a selective inhibitor of phosphodiesterase-III with
      antiplatelet, antithrombotic and vasodilating properties. It also exhibits
      antiproliferative effects on smooth muscle cells and has beneficial effects on
      high density lipoprotein-cholesterol and triglyceride levels.Randomized, double
      blind, placebo-controlled 12- to 24-week trials in >2000 patients with moderate
      to severe intermittent claudication demonstrated that cilostazol generally
      significantly increased walking distances and improved quality of life compared
      with placebo. Additionally, a large comparative 24-week trial showed that
      cilostazol 100 mg twice daily was significantly more effective than
      pentoxifylline 400mg three times daily (pentoxifylline was not significantly
      different from placebo). Cilostazol was generally well tolerated. Adverse events
      reported significantly more often with cilostazol than with placebo included
      headache, diarrhea, abnormal stools, infection, rhinitis and peripheral edema and
      in comparison with pentoxifylline were headache, diarrhea, abnormal stools and
      palpitations. Adverse events were generally mild to moderate in intensity,
      transient or resolved after symptomatic treatment and rarely required treatment
      withdrawal. Significant drug interactions are observed when cilostazol is
      coadministered with other agents that inhibit cytochrome P450 (CYP) 3A4 (e.g.
      erythromycin or diltiazem) or CYP2C19 (e.g. omeprazole). As a result, in Europe
      cilostazol is contraindicated in patients receiving CYP3A4 or CYP2C19 inhibitors
      and in the US it is recommended that dosage reduction for cilostazol be
      considered during coadministration of cilostazol and CYP3A4 or CYP2C19
      inhibitors. Conversely, cilostazol itself does not appear to inhibit CYP3A4.
      Coadministration of cilostazol with aspirin or warfarin did not result in any
      clinically significant changes to coagulation parameters, bleeding time or
      platelet aggregation. CONCLUSION: In six of eight well designed clinical trials,
      cilostazol was significantly more effective than placebo in increasing walking
      distances and improving the quality of life of patients with moderate to severe
      intermittent claudication. In addition, limited comparative data have shown that
      cilostazol has superior efficacy compared with pentoxifylline. Cilostazol is also
      generally well tolerated. Additional comparative trials are required to confirm
      these results, to determine the place of cilostazol in relation to other agents
      or exercise therapy and risk factor reduction alone, and to establish the effects
      of long-term treatment with cilostazol in patients with intermittent
      claudication. Cilostazol is contraindicated in several subpopulations of
      patients, particularly those with congestive heart failure and severe hepatic or
      renal impairment. Nonetheless, current data support the choice of cilostazol as a
      promising therapy amongst the limited options available for patients with
      intermittent claudication.

PMID- 14727940
TI  - Opinion and evidence in cardiovascular therapeutics.
AB  - Cardiovascular therapeutics is a vast and evolving area for researchers, primary
      care physicians and specialists. To help keep you up-to-date with the latest
      advances worldwide on all aspects of drug therapy and management of
      cardiovascular disorders, this section of the journal brings you information
      selected from the drug therapy reporting service Inpharma Weekly. The following
      reports are selected from the latest issues, summarizing the most important
      research and development news, clinical studies, treatment guidelines,
      pharmacoeconomic and adverse reaction news, and expert opinion pieces published
      across a broad range of literature sources.

PMID- 14727941
TI  - Does ischemic preconditioning afford clinically relevant cardioprotection?
AB  - This paper reviews significant work which has been done on ischemic
      preconditioning since its introduction by Murry et al. in 1986. This is a
      phenomenon where myocardial cells gain protection against long periods of
      ischemia by initially being exposed to brief episodes of ischemia followed by
      reperfusion. The molecular basis of ischemic preconditioning where adenosine,
      bradykinin and opioids are released, and eventually lead to the opening of
      mitochondrial ATP-sensitive potassium channels, is discussed in detail. There
      have been over 33 clinical studies to assess the clinical relevance of ischemic
      preconditioning. Many of these studies have looked at its benefit in patients
      undergoing percutaneous transluminal coronary angioplasty; others have looked at
      its use in open-heart surgery. There is no doubt that many of these studies
      support the clinical relevance of ischemic preconditioning, however, most of
      these studies have looked at surrogate markers, such as cardiac enzyme release,
      and left ventricular ejection fraction, but very few looked at the original
      endpoint, described by Murry et al., which is cell death. Larger trials, with
      morbidity and mortality being with the primary endpoints, are needed to confirm
      the clinical relevance of ischemic preconditioning.

PMID- 14727942
TI  - Vasopressin receptor antagonists. Therapeutic potential in the management of
      acute and chronic heart failure.
AB  - Despite the use of ACE inhibitors and beta-blockers, the morbidity and mortality
      of patients with chronic heart failure remains quite high. This has stimulated
      the development of new therapies, many based on the neurohormonal hypothesis.
      There are now multiple agents being developed for the treatment of heart failure
      designed to block many of the neurohormones that are increased in these patients.
      One of the hormones that is increased in chronic heart failure is vasopressin.
      Vasopressin reduces free water secretion and at high concentrations, causes
      vasoconstriction in the peripheral vasculature. Antagonists to vasopressin will
      promote free water excretion (aquaresis) and vasodilatation with a subsequent
      reduction in afterload. In theory, these agents would be beneficial for both
      acute exacerbations of heart failure (free water excretion) and chronic heart
      failure (neurohormonal blockade). We review the potential uses of these
      antagonists for these two conditions and the promising results of small,
      hemodynamic trials with the new vasopressin antagonists that have already been
      performed.

PMID- 14727943
TI  - Hypertensive emergencies. Etiology and management.
AB  - Although systemic hypertension is a common clinical disorder, hypertensive
      emergencies are unusual in clinical practice. Situations that qualify as
      hypertensive emergencies include accelerated or malignant hypertension,
      hypertensive encephalopathy, acute left ventricular failure, acute aortic
      dissection, pheochromocytoma crisis, interaction between tyramine-containing
      foods or drugs and monoamine oxidase inhibitors, eclampsia, drug-induced
      hypertension and possibly intracranial hemorrhage. It is important to recognize
      these conditions since immediate lowering of systemic blood pressure is
      indicated. The diagnosis of hypertensive emergencies depends on the clinical
      manifestations rather than on the absolute level of the blood pressure. Depending
      on the target organ that is affected, the manifestations of hypertensive
      emergencies can be quite expressive, yet variable. Thus, the physician has to
      make the clinical diagnosis urgently in order to render appropriate therapy.
      Several parenteral drugs can quickly and effectively lower the blood pressure in
      hypertensive emergencies. Intravenous fenoldopam, a selective dopamine (DA1)
      receptor agonist, offers the advantage of improving renal blood flow and causing
      natriuresis. Intravenous nicardipine may be beneficial in reserving tissue
      perfusion in patients with ischemic disorders. Whereas trimethaphan camsilate is
      the drug of choice for managing acute aortic dissection, hydralazine remains the
      drug of choice for the treatment of eclampsia. The alpha-adrenoceptor,
      phentolamine, is useful in patients with pheochromocytoma crisis. Enalaprilat is
      the only ACE inhibitor available for parenteral use and may be particularly
      useful in treating hypertensive emergencies in patients with heart failure.
      However, ACE inhibitors may cause a precipitous fall in blood pressure in
      patients who are hypovolemic. Although useful as adjunctive therapy in
      hypertensive crises, diuretics should be used with caution in these patients
      because prior volume depletion may be present in some conditions such as
      malignant hypertension. The treating physician should be familiar with the
      pharmacological and clinical actions of drugs which are indicated for and useful
      in the treatment of hypertensive emergencies. Once the patient's situation has
      stabilized, the patient may be switched to an oral medication and the physician
      should discuss long term follow up plans. With appropriate clinical diagnosis,
      hypertensive emergencies can be successfully treated and the complications can be
      prevented with timely intervention.

PMID- 14727944
TI  - Defining the role of calcium channel antagonists in heart failure due to systolic
      dysfunction.
AB  - Calcium channel antagonists (CCAs) may either be divided into the
      dihydropyridines (e.g. amlodipine, felodipine, isradipine, lacidipine,
      nilvadipine, nifedipine, nicardipine etc.), the phenylalkylamines (e.g.
      verapamil) and the benzothiazepines (e.g. diltiazem) according to their chemical
      structure, or into first generation agents (nifedipine, verapamil and diltiazem)
      and second generation agents (subsequently developed dihydropyridine
      derivatives). Second generation CCAs are characterized by greater selectivity for
      calcium channels in vascular smooth muscle cells than the myocardium, a longer
      duration of action and a small trough-to-peak variation in plasma concentrations.
      Heart failure is characterized by decreased cardiac output resulting in
      inadequate oxygen delivery to peripheral tissues. Although the accompanying
      neurohormonal activation, leading to vasoconstriction and increased blood
      pressure, is initially beneficial in increasing tissue perfusion, prolonged
      activation is detrimental because it increases afterload and further reduces
      cardiac output. At the level of the myocyte, heart failure is associated with
      increased intracellular calcium levels which are thought to impair diastolic
      function. These changes indicate that the CCAs would be beneficial in patients
      with heart failure. There has been a strong interest and increasing experience in
      the use of CCAs in patients with heart failure. Despite potential beneficial
      effects in initial small trials, findings from larger trials suggest that CCA may
      have detrimental effects upon survival and cardiovascular events. However, this
      may not necessarily be a 'class b' effect of the CCAs as there is considerable
      heterogeneity in the chemical structure of individual agents. Clinical experience
      with different CCAs in patients with heart failure includes trials that evaluated
      their effects on hemodynamic parameters, exercise tolerance and on
      symptomatology. However, the most relevant results are those from randomized
      clinical trials that assessed mortality as the primary endpoint. First generation
      CCAs have direct negative inotropic effects and even sustained release
      formulations have not proved any beneficial effect upon survival. With second
      generation CCAs, some benefit on hemodynamic parameters has been observed but
      none on survival, alone or in combination with ACE inhibitors. It is noteworthy
      that although amlodipine had a neutral effect on morbidity and mortality in
      large, randomized, placebo-controlled trials in patients with heart failure, the
      drug was well tolerated. There is no specific indication for CCAs (first or
      second generation) in patients with systolic heart failure, alone or in
      combination with ACE inhibitors, but amlodipine may be a considered in the
      management of hypertension or coronary artery disease in patients with heart
      failure.

PMID- 14727945
TI  - Photopheresis. Therapeutic potential in preventing restenosis after percutaneous
      transluminal coronary angioplasty.
AB  - Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy
      that entails the reinfusion of peripheral blood mononuclear cells after exposure
      to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation.
      Currently available at approximately 150 treatment centers worldwide,
      photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell
      lymphoma (CTCL) and has also shown promise in treating nonmalignant immune
      related conditions such as organ transplant rejection, acute and chronic graft
      versus-host disease, and autoimmune disorders. The precise mechanism by which
      photopheresis evokes clinical responses is unknown, although this modality seems
      capable of modulating T-cell and monocyte activity. Clinical and laboratory
      findings suggest that the reinfusion of peripheral blood mononuclear cells after
      exposure to UVA-activated methoxsalen engenders an immune response against
      proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin
      that is biologically inert until exposed to UVA radiation at the proper
      wavelength, at which time it irreversibly cross-links DNA thymine bases and
      arrests cell proliferation. T cells isolated from the peripheral blood of
      patients after photopheresis demonstrate significantly increased levels of
      apoptosis, whereas macrophages and dendritic cells exhibit the ability to
      phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the
      uptake, processing, and presentation of distinctive antigens from apoptotic
      pathogenic T cells by macrophages and dendritic cells leading to the induction of
      an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of
      apparently opposite immune processes (i.e. upregulation of an antitumor response
      and downregulation of allogeneic or autoimmune responses) can be explained by its
      ability to target either a single malignant T-cell clone (as in CTCL) or multiple
      activated T-cell clones (as in organ transplant rejection, graft-versus-host
      disease, or autoimmune disease). Because acute inflammation and T-cell activation
      may be important in the pathogenesis of restenosis following percutaneous
      transluminal coronary angioplasty (PTCA), photopheresis was used for the first
      time at our center to prevent restenosis. A total of 78 patients with single
      vessel coronary artery disease amenable to PTCA with or without stent deployment
      were enrolled, 41 in the control group and 37 in the photopheresis group.
      Clinical restenosis occurred in significantly less photopheresis patients than
      control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95%
      confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA
      recommended protocol is currently underway to better determine what, if any,
      impact photopheresis has in preventing restenosis.

PMID- 14727947
TI  - Ezetimibe.
AB  - Ezetimibe, a synthetic 2-azetidinone, is the first of a new class of compounds
      that selectively inhibits the absorption of cholesterol and related plant sterols
      in the intestine. The drug, and its glucuronyl metabolite, are thought to inhibit
      a putative cholesterol transporter of enterocytes, located within the brush
      border membrane of the small intestine. In large, randomized, placebo-controlled,
      12-week trials, ezetimibe reduced levels of low density lipoprotein-cholesterol
      (LDL-C) by approximately 18%; triglyceride levels were reduced by approximately
      6% in one trial but not another. Ezetimibe produced a modest increase in levels
      of high density lipoprotein-cholesterol. Moreover, reductions in LDL-C and
      triglyceride levels were greater in patients treated with ezetimibe
      coadministered with a statin (lovastatin, pravastatin, atorvastatin or
      simvastatin), than with either of those agents given alone. The coadministration
      of the lowest statin dose and ezetimibe produced similar LDL-C reductions to the
      administration of the highest statin dose alone. Ezetimibe also provided
      beneficial effects on plasma lipid levels when administered to patients with
      hypercholesterolemia already receiving a statin. Ezetimibe plus a statin reduced
      LDL-C levels more than the maximum statin dose alone in a trial in patients with
      homozygous familial hypercholesterolemia and was effective in a placebo
      controlled trial in patients with homozygous sitosterolemia. The drug was well
      tolerated in clinical studies conducted to date. In large, randomized, double
      blind trials, ezetimibe had a similar tolerability profile to that of placebo.
      Coadministration of ezetimibe and a statin did not increase the incidence of
      adverse events related to statin monotherapy.

PMID- 14727946
TI  - Optimal therapy of low levels of high density lipoprotein-cholesterol.
AB  - Plasma levels of high-density lipoprotein-cholesterol (HDL-C) are a powerful
      independent cardiovascular risk factor, bearing an inverse relationship with
      atherosclerotic cardiovascular disease (with risk rising sharply when levels are
      <1.04 mmol/L). Apart from its protective role in atherosclerosis, HDL-C increases
      fibrinolysis, is an antioxidant to low density lipoprotein-cholesterol (LDL-C),
      and decreases platelet aggregability. Up to a third of patients with
      atherosclerotic cardiovascular disease have 'desirable' plasma levels of total
      cholesterol but low HDL-C levels. Benefits of treating low plasma HDL-C levels
      were clearly demonstrated in the Veterans Affairs HDL Intervention Trial (VA-HIT)
      where gemfibrozil reduced nonfatal infarcts and coronary deaths by 22%. This was
      achieved by a 6% increase in plasma HDL-C levels, and a 24.5% decrease in plasma
      levels of triglycerides, without any significant decrease in LDL-C levels.
      Multivariate analyses revealed the rise in plasma HDL-C levels after treatment,
      but not decreases in plasma levels of triglycerides or LDL-C, predicted coronary
      artery disease events. The typical patient under consideration in this article is
      one with plasma levels of HDL-C <1 mmol/L, LDL-C <3.37 mmol/L [either receiving
      therapeutic lifestyle changes or or LDL-C-lowering therapy comprising a
      hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor or bile acid
      sequestrant] and fasting triglycerides <2.26 mmol/L. We propose this dyslipidemia
      be classified as Type VI phenotype following the Frederickson and Lees
      classification. High-risk patients (with >/=2 risk factors for atherosclerotic
      cardiovascular disease, or 10-year cardiovascular risk >20%), patients with
      established atherosclerotic cardiovascular disease, or type 2 diabetes mellitus,
      or metabolic syndrome should receive pharmacotherapy. Plasma HDL-C levels >1.16
      mmol/L may be considered optimal and between 1 and 1.16 mmol/L as desirable.
      Fibric acid derivatives, nicotinic acid, HMG-CoA reductase inhibitors, estrogens,
      and ethanol (not recommended as therapy) increase plasma HDL-C levels. Nicotinic
      acid is the most potent agent and recent reports indicate that, in contrast to
      gemfibrozil, it selectively increases antiatherogenic HDL subfraction,
      lipoprotein (Lp) AI (without apolipoprotein AII), in patients with low plasma HDL
      C levels. An extended-release formulation, administered once daily, has improved
      the tolerability of nicotinic acid. Recent evidence also indicates that nicotinic
      acid may effectively correct dyslipidemia in patients with diabetes mellitus
      without significantly compromising glycemic control. Fibric acid derivatives and
      estrogen raise plasma HDL-C levels by different mechanisms of action, and these
      agents may be used with nicotinic acid. Combination therapy (especially HMG-CoA
      reductase inhibitor and nicotinic acid) should be considered in patients with
      atherosclerotic cardiovascular disease and low plasma HDL-C levels.

PMID- 14727951
TI  - Development of radiocontrast agents for vascular imaging: progress to date.
AB  - The revolution in molecular imaging techniques is profoundly changing the
      understanding of the pathophysiology and treatment of atherosclerosis. With these
      rapid changes there is an increasing demand for development of sensitive and well
      tolerated novel imaging agents that can be rapidly translated from small animal
      models into patients with atherosclerosis. Nuclear medicine and positron emission
      tomography techniques have the ability to detect and serially monitor a variety
      of biologic and pathophysiologic processes usually with tracer quantities of
      radiolabeled peptides, drugs, and other molecules at dosages free of
      pharmacologic adverse effects unlike the current generation of intravenous agents
      required for magnetic resonance imaging (MRI) and computed axial tomography (CT)
      scanning. A representative sampling of the wide array of radiopharmaceuticals
      developed specifically for radionuclide imaging of atherosclerosis, that have
      been approved for clinical use and those in pre-clinical trials, have been
      reviewed in this article. The presence of an inflammatory stimulus increases
      expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on
      monocytes and macrophages, and somatostatin receptors on T lymphocytes.
      Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to
      CCR-2 and can be used to detect subacute and chronic inflammatory lesions.
      Similarly, radiolabeled octreotide or depreotide can be used to detect activated
      T lymphocytes which may identify the vulnerable plaque. Animal models indicate
      that (99m)Tc-annexin V, (125)I-MCP-1 and [(18)F]-fluoro-2-deoxyglucose are
      effective in identifying apoptotic cell death, macrophage infiltration and
      metabolic activity in atheromatous lesions, respectively. Expression of
      alpha(v)beta(3) integrin is increased in activated endothelial cells and vascular
      smooth muscle cells after vascular injury, and alpha(v)beta(3) integrin is
      minimally expressed on smooth muscle cells and is not expressed on quiescent
      epithelial cells. Radiolabeled high-affinity peptides can be used to target the
      alpha(v)beta(3) integrin and visualize areas of vascular damage. Advances in
      technology such as the micro-single photon emission computed tomography
      (microSPECT) have the potential to overcome the drawbacks of older CT and MRI
      methodologies, such as lack of biologically relevant ligands and compatible blood
      pool contrast agents for imaging. Despite these advances in imaging technology,
      the small size of atheromatous lesions makes it difficult to detect using
      external imaging techniques. Therefore, recently there has been renewed interest
      in the use of intravascular catheter-based radiation detectors.

PMID- 14727952
TI  - Therapeutic potential of monoclonal antibodies in myocardial reperfusion injury.
AB  - While reperfusion therapy in myocardial infarction is associated with better
      short- and long-term outcomes, it paradoxically results in reperfusion injury
      mediated by interactions between leukocytes, endothelial cells, platelets, and
      the myocardium. Several surface receptors, adhesion molecules, and ligands have
      been shown to be important in the pathogenesis of myocardial reperfusion injury,
      and therapeutic strategies employing the use of monoclonal antibodies have been
      attempted against many of them. These have included monoclonal antibodies against
      activated complement 5 (C5a) to inhibit leukotaxis, monoclonal antibodies against
      P-selectin, P-selectin glycoprotein ligand (PSGL)-1, L-selectin and E-selectin to
      inhibit leukocyte rolling, and monoclonal antibodies against the Mac-1
      (CD11b/CD18) receptor and intercellular adhesion molecule (ICAM)-1 to block firm
      adhesion of leukocytes to endothelial cells. In addition, although initially
      developed as an antiplatelet agent, the glycoprotein IIb/IIIa receptor antagonist
      abciximab shows significant ability to diminish or prevent reperfusion injury,
      presumably through its ability to block the Mac-1 receptor on leukocytes.
      Finally, monoclonal antibodies have also been tested against several cytokines
      and adhesion molecules implicated in so-called subacute endothelial activation,
      including interleukin-8 and vascular cell adhesion molecule (VCAM)-1. Studies in
      animals evaluating the use of monoclonal antibodies in reperfusion injury against
      various potential targets have largely been successful; however, studies in
      humans have been disappointing, underscoring the pitfalls of using animal models
      for the study of complex diseases. Based upon current knowledge, it is becoming
      clear that a successful strategy against reperfusion injury will require
      targeting several pathways at once, rather than attempting to block one final
      common pathway. In addition, inhibition of subacute endothelial activation
      through inhibition of transcription factors, namely nuclear factor (NF)-kappa B,
      may be a prerequisite to significantly reducing the extent of myocardial damage
      in this condition. The future of monoclonal antibodies in the overall strategy
      remains unclear. Newer small molecule inhibitors are also under development, and
      the eventual role of gene therapy remains to be elucidated.

PMID- 14727953
TI  - Strategies for minimizing hyperlipidemia after cardiac transplantation.
AB  - Allograft coronary artery disease represents a major limitation to long-term
      survival after cardiac transplantation. Hyperlipidemias have been linked to the
      development of native coronary atherosclerosis, and hyperlipidemic states have
      correlated with the severity of allograft coronary artery disease. Heart
      transplant recipients typically manifest increases in plasma levels of total
      cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides
      within the first 3-12 months following transplantation. Factors known to promote
      post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine
      (interference with clearance and increased oxidizability of LDL), sirolimus
      (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which
      contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A
      (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following
      cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol
      levels and is associated with a decreased incidence and progression of allograft
      coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are
      metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine,
      increasing the risk of myostitis when they are used in large dosages with
      cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in
      heart transplant recipients. Gemfibrozil has proved effective in transplant
      recipients when there is isolated marked elevation of plasma triglyceride levels.
      When hyperlipidemia persists despite therapy, some benefit may result with
      conversion from cyclosporine to tacrolimus. Although a definitive link between
      hyperlipidemia and allograft coronary disease has yet to be proven, available
      evidence points to abnormal lipid metabolism as part of the complex etiologic
      machinery driving the process of 'chronic rejection'. Consensus exists within the
      transplant community that a HMG-CoA reductase inhibitor such as pravastatin,
      should be part of the routine post-transplant drug regimen, and persistent
      hyperlipidemia should be aggressively treated.

PMID- 14727954
TI  - Racial differences in responses to drug treatment: implications for
      pharmacotherapy of heart failure.
AB  - Chronic heart failure (CHF) is a common disease with high associated morbidity
      and mortality, and the outcome appears to be worse in black compared with white
      patients. There is currently no clear consensus for basing the pharmacological
      treatment of CHF on racial differences. Most studies that have investigated the
      potential effects of racial differences on pharmacological responses in heart
      failure have been based on African Americans and white participants. Using these
      data, this review will discuss the current understanding of the effects of racial
      differences in response to pharmacotherapy in heart failure, possible mechanisms
      for these observed differences, and how this may impact on patient management.
      Diuretics have favorable symptomatic benefits in both black and white patients
      with heart failure with evidence of fluid retention. ACE inhibitors seem to be
      less effective in the treatment of black patients with heart failure compared
      with white patients. This may be due to low pre-existing activity of the renin
      angiotensin system in blacks. The role of angiotensin receptor blockers (ARBs) in
      the management of all patients with heart failure is incompletely defined and
      there are no clear trial data to show any difference in effect between black and
      white patients with heart failure. There is good evidence for the use of
      spironolactone in all patients with heart failure, but no evidence for a
      different effect in black patients. Similarly, there is no conclusive data to
      suggest a difference in effect of digoxin in different racial groups. The
      evidence available would suggest that certain beta-adrenoceptor antagonists
      (certainly carvedilol but not bucindolol) are effective in both black and white
      patients with CHF. The combination of hydralazine and nitrates would appear to be
      particularly effective in black patients with CHF though the African American
      Heart Failure Trial (A-HeFT) trial should provide clearer evidence for the
      potentially greater beneficial effects of these two drugs in the black
      population. It is important to accept that racial categorization acts as only a
      surrogate marker for genetic or other factors responsible for individual
      responses to drug therapy and that any identified differences will not apply to
      all members of each stratified group. Nonetheless, in managing a complex, common
      and often fatal condition such as heart failure, recognizing potential individual
      differences in drug responses should enable the responsible clinician to provide
      a tailored and evidence-based approach to patient treatment.

PMID- 14727955
TI  - Turner syndrome and the heart: cardiovascular complications and treatment
      strategies.
AB  - Turner syndrome is a condition usually associated with reduced final height,
      gonadal dysgenesis, and thus insufficient circulating levels of female sex
      steroids, and infertility. A number of other signs and symptoms are seen more
      frequently with the syndrome. With respect to cardiac function, congenital
      malformations of the heart and the great vessels, hypertension and ischemic heart
      disease, and increased risk of aortic dissection are all conditions that the
      pediatrician or the physician caring for females with Turner syndrome should keep
      in mind. Many girls and adolescents with Turner syndrome receive growth hormone
      (GH) treatment, which has so far been an effective and well-tolerated therapy.
      Nevertheless, because of the experience from acromegaly, the physician should
      monitor blood pressure and perform echocardiography, together with clinical
      examinations by a cardiologist at regular intervals. During adulthood most women
      with Turner syndrome are faced with premature menopause and the need for female
      hormone replacement therapy (HRT). During clinical evaluation of girls and women
      with Turner syndrome, these conditions and complications should be kept under
      surveillance. Here the cardiovascular complications of Turner syndrome are
      reviewed. The risk of congenital heart defects such as bicuspid aortic valves,
      aortic coarctation, other valve abnormalities, and septal defect is increased.
      Likewise, the risk of aortic dissection at a young age is increased, as is the
      risk of hypertension, ischemic heart disease, and stroke. GH therapy does not
      seem to adversely affect the heart, although longer-term follow-up studies are
      needed. In short-term studies, HRT lowers blood pressure, while any effect on the
      risk of ischemic heart disease has not been evaluated. Treatment with GH and HRT
      are discussed in relation to the heart and great vessels. Presently, the
      pathophysiology of the congenital cardiovascular malformation in Turner syndrome
      is unexplained, although different theories exist. Recommendations for clinical
      practice are given, including life-long surveillance of cardiac function, aortic
      diameter and blood pressure.

PMID- 14727956
TI  - Calcium channel antagonists in the treatment of hypertension.
AB  - Calcium channel antagonists are widely used antihypertensive agents. Their
      popularity among primary care physicians is not only due to their blood pressure
      lowering effects, but also because they appear to be effective regardless of the
      age or ethnic background of the patients. The first available calcium channel
      antagonists utilized immediate-release formulations which, although effective in
      patients with angina pectoris, were not approved by the US FDA for use in
      hypertension. When long-acting once-daily formulations were approved in this
      indication, the short-acting preparations--which had by then become generic and
      inexpensive--retained some residual unapproved use for hypertension. An
      observational case-controlled trial, based on such usage, noted that these agents
      were associated with a greater risk of myocardial infarctions than conventional
      agents such as diuretics and beta-adrenoceptor antagonists. Further case
      controlled trials showed, in fact, that the dangers of calcium channel
      antagonists were confined to the short-acting agents and that approved long
      acting agents were at least as well tolerated and effective as other
      antihypertensive drugs. Cardiovascular outcomes during treatment with calcium
      channel antagonists have been examined in randomized, controlled trials. Compared
      with placebo, the calcium channel antagonists clearly prevented strokes and other
      cardiovascular events and reduced mortality. The effects of these agents on
      survival and clinical outcomes were similar to those with other antihypertensive
      drugs. There is a slight tendency for the calcium channel antagonists to be more
      effective than other drug types in preventing stroke, but slightly less effective
      in preventing coronary events. These observations extend to high-risk patients
      with hypertension including those with diabetes mellitus. Even so, patients with
      evidence of nephropathy should not receive monotherapy with calcium channel
      antagonists. Such patients are optimally treated with angiotensin receptor
      antagonists or ACE inhibitors, although addition of other drugs, including
      calcium channel antagonists, is often required to achieve the tight blood
      pressure control necessary to provide adequate renal protection. Calcium channel
      antagonists have a highly acceptable tolerability profile and careful reviews of
      available data have shown that their use is not associated with increased
      bleeding or promotion of tumor formation. It is now recognized that reduction of
      blood pressure in patients with hypertension to levels often <130/85 mm Hg should
      be undertaken in presence of other cardiovascular risk factors or evidence of end
      organ damage. Because of this important concept, calcium channel antagonists,
      like the other antihypertensive drug classes, are progressively being prescribed
      less often as monotherapy, but more typically as part of combination regimens.

PMID- 14727958
TI  - Pharmacogenetics, pharmacogenomics, and cardiovascular therapeutics: the way
      forward.
AB  - The completion of sequencing of the human genome will be the vanguard for
      numerous advances in medicine. The first discernible application is likely to
      occur in pharmacogenomics, a field focused on the influence of genetic
      differences on the variability in patients' response to medications. While an
      inherited basis for drug response has been recognized for some time, it is the
      confluence of molecular biology, high-throughput genotyping, and bioinformatics
      that has made it practical to study the genetic basis of variability to
      medications on a large scale. Pharmacogenomics may enable clinicians to
      prospectively identify patients most likely to derive benefit from a drug, with
      minimal likelihood of adverse events. This DNA-based approach to predicting
      clinical drug efficacy and toxicity would shift the current prescribing paradigm
      from its empirical nature to a more patient-specific model, ushering in a new era
      of personalized medicine. Polymorphisms in drug metabolizing enzymes, drug
      targets, and disease pathogenesis genes are associated with therapeutic effect to
      cardiovascular pharmacotherapy. Moreover, pharmacogenomics and functional
      genomics are expected to have a profound impact on the process of drug discovery
      and development. Finally, pharmacogenomics is likely to transform the way
      clinical trials are conducted by allowing for the selection of a more homogeneous
      study population, thereby reducing the size and cost of clinical investigation.

PMID- 14727959
TI  - Therapeutic potential of implantable replacement hearts.
AB  - In patients hospitalized with decompensated life-threatening heart failure, the
      impact of newer pharmacologic therapies and mechanical circulatory support has
      not yet been realized, except for those who are bridged to cardiac
      transplantation. For long-term support of transplant-ineligible patients who have
      severe biventricular failure that is refractory to optimized pharmacologic
      therapy, replacement of the natural heart with a totally implantable mechanical
      replacement heart, capable of producing blood flow of up to 8 to 10 L/min, may
      become the most well tolerated and effective treatment. This article summarizes
      the current status of the first generation implantable replacement heart (AbioCor
      trade mark, ABIOMED. Inc., Danvers, MA). With regard to optimizing the further
      enhancement of treatment options for end-stage heart failure and other life
      threatening illnesses, the pharmacodynamics-like principle of therapeutic
      efficiency should play a role in the development of both drugs and devices. In
      keeping with that principle, we recommend that adjusting a product's design input
      requirements to maximize the therapeutic effect per exposure and;to separate the
      cumulative therapeutic effects of the product from the cumulative adverse effects
      (of the product, and of the comorbid disease processes in the patients treated)
      should be part of the good product development process for any therapeutic
      product.

PMID- 14727960
TI  - Combination therapy for ischemic stroke: potential of neuroprotectants plus
      thrombolytics.
AB  - Thrombolysis improves clinical outcome in patients with acute ischemic stroke.
      However, only a small fraction of patients receive thrombolytic therapy due to
      the narrow therapeutic time window available for the treatment in patients with
      ischemic stroke. A better understanding of the mechanisms underlying ischemic
      injury may lead to the development of novel therapeutic strategies to reduce
      brain damage after stroke. Cerebral ischemia triggers a number of
      pathophysiological and biochemical changes in the brain that present potential
      targets for therapeutic intervention. Candidate pathways include those regulating
      cellular calcium influx, excitatory neurotransmitter uptake, and generation of
      reactive oxygen species, as well as activation of enzymes including kinases,
      proteases, and lipases. The end result of these pathophysiological pathways may
      be apoptosis (programmed cell death) or necrosis. The activation of inflammatory
      cascades following ischemia also contributes to brain injury. Several
      neuroprotective agents which block cell death pathways have been proposed to have
      therapeutic potential in patients with stroke including calcium channel
      antagonists, glutamate receptor antagonists, free radical scavengers, anti
      inflammatory strategies, inhibitors for nitric oxide synthase, and growth
      factors. Although results from clinical trials to date have been disappointing,
      there is reason to believe that combination therapy involving both thrombolytics
      and neuroprotectants holds promise for stroke treatment and warrants further
      investigation.

PMID- 14727961
TI  - Optimizing the use of abciximab and intracoronary stents in patients with acute
      ST elevation myocardial infarction.
AB  - Acute ST elevation myocardial infarction (STEMI) is a cause of significant
      morbidity and mortality in patients with coronary artery disease. Reperfusion
      therapy, either with thrombolytic agents or primary percutaneous coronary
      intervention (PCI), is the mainstay of therapy. Worldwide, systemic thrombolysis
      is the more commonly utilized reperfusion strategy, although an increasing number
      undergo primary PCI. PCI techniques and adjuvant therapies are evolving. Stents
      appear to be more useful than thrombolytic therapy or PTCA in acute AMI,
      especially in decreasing the need for subsequent target lesion revascularization.
      In patients with STEMI, administration of abciximab with stent placement
      decreased the primary endpoint [composite of major adverse cardiac events (death,
      reinfarction, urgent TVR)] by over 50% at 30 days in the Abciximab before Direct
      angioplasty and stenting in acute Myocardial Infarction Regarding Acute and Long
      term follow-up (ADMIRAL) trial, and the benefit appeared to be maintained at 6
      months. Despite these promising results, administration of abciximab with a stent
      did not afford greater benefit over stent alone in the Controlled Abciximab and
      Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
      The apparent lack of benefit with abciximab in the CADILLAC trial may be
      explained by the fact that this trial was not powered to detect differences in
      mortality and enrolled patients were selected after angiography, and were thus at
      lower risk. The adjuvant therapies of intracoronary stents and abciximab are
      becoming the standard of care, based on multiple studies. Stent placement during
      STEMI decreases the risk of restenosis and TVR. Treatment with abciximab may
      reduce the risk of acute adverse events in the short term.

PMID- 14727962
TI  - Prevention of restenosis with antioxidants: mechanisms and implications.
AB  - The aim of this review is to give an overview of the field of restenosis
      prevention with antioxidants, put in the perspective of their potential use for
      the prevention of atherosclerosis progression. Compelling evidence points to
      oxidative stress as an important trigger in the complex chain of events leading
      to atherosclerosis. There is also evidence that oxidative stress occurs early
      after angioplasty. Reactive oxygen species (ROS) can induce endothelial
      dysfunction and macrophage activation, resulting in the release of cytokines and
      growth factors that stimulate matrix remodeling and smooth muscle cell
      proliferation. The accumulation of new extracellular matrix and smooth muscle
      cells will result in the neointimal formation responsible for lumen narrowing
      after stent deployment and which contributes to that after balloon angioplasty.
      In addition, oxidation processes are involved in the cross-linking of collagen
      fibers, and this coupled with smooth muscle cell contraction and endothelial
      dysfunction may result in long-term vascular constriction or lack of adaptive
      vascular remodeling after balloon angioplasty. The powerful antioxidant probucol
      has been shown to prevent coronary restenosis after balloon angioplasty in the
      Multivitamins and Probucol (MVP) trial and other clinical studies. However,
      prolongation of the QT interval with probucol remains a long-term safety concern.
      AGI-1067, a metabolically stable analog of probucol, is a vascular protectant
      with strong antioxidant properties as potent to those of probucol. There has been
      no evidence of prolongation of the QT interval with AGI-1067 in initial clinical
      studies. The anti-restenosis properties of AGI-1067 are being assessed in the
      Canadian Antioxidant Restenosis Trial (CART)-1. Considering that oxidative stress
      and inflammation may persist for a prolonged period after stent placement,
      treatment with AGI-1067 for the entire period of risk after percutaneous coronary
      intervention (PCI) [instead of only 4 weeks in CART-1] may result in enhanced
      protection against luminal renarrowing. This hypothesis will be tested in the
      randomized, multicenter CART-2 trial. AGI-1067 has been effective at preventing
      atherosclerosis in all tested animal models, including the low density
      lipoprotein receptor-deficient and apo-E knockout mice. This has potentially
      important implications, as PCI and local approaches to prevent restenosis such as
      coated stents are not expected to prevent atherosclerosis progression, myocardial
      infarction and cardiovascular death. As the ultimate goal of therapy for patients
      with coronary artery disease must remain prevention of disease progression and
      atherosclerosis-related events, CART-2 will test the value of AGI-1067 for the
      reduction of both post-PCI restenosis and atherosclerosis progression.

PMID- 14727963
TI  - Bosentan.
AB  - Bosentan is a nonpeptide, specific, competitive, dual antagonist at both
      endothelin receptor subtypes (ET(A) and ET(B)). Orally administered bosentan
      effectively prevents endothelin 1-induced vasoconstriction in pulmonary vessels
      in patients with pulmonary arterial hypertension. Improvement in exercise
      capacity from baseline was significantly greater with bosentan than with placebo
      in two phase III trials in patients with WHO functional class III or IV pulmonary
      arterial hypertension (primary or associated with connective tissue disease)
      despite treatment with vasodilators, diuretics, anticoagulants, cardiac
      glycosides, or supplemental oxygen. The beneficial effects of bosentan on
      exercise capacity were maintained for at least 20 weeks. Compared with placebo,
      bosentan led to a significantly greater improvement from pretreatment values in
      secondary efficacy endpoints such as the Borg dyspnea index, WHO functional
      class, and cardiopulmonary hemodynamic parameters (cardiac index, pulmonary
      vascular resistance, pulmonary artery pressure, pulmonary capillary wedge
      pressure, mean right atrial pressure). Bosentan significantly reduced the
      incidence, and delayed the onset, of clinical worsening of pulmonary arterial
      hypertension compared with placebo. In published clinical trials, adverse events
      that occurred with similar or greater frequency with bosentan 125 mg twice daily
      than with placebo included headache, syncope, flushing and abnormal hepatic
      function. Those that occurred less frequently with bosentan 125 mg twice daily
      than with placebo included dizziness, worsening of symptoms of pulmonary arterial
      hypertension, cough and dyspnea.

PMID- 14727967
TI  - Cardiac resynchronization therapy in patients with chronic heart failure:
      pathophysiology and current experience.
AB  - Congestive heart failure afflicts 2 to 4 million people in the US and nearly 15
      million people worldwide. Accepted goals of heart failure treatment include:
      improvement of symptoms;prevention of disease progression; and reduction in
      morbidity and mortality. Complex pharmacological therapies achieve these goals,
      but not in all patients with heart failure. Cardiac resynchronization therapy
      (CRT) represents a new therapeutic approach in patients with chronic heart
      failure. CRT is only applicable to a subgroup of patients with ventricular
      conduction system delay, characterized by prolonged QRS duration. Bundle branch
      block impacts 20 to 30% of patients with New York Heart Association (NYHA)
      functional class III-IV heart failure and consists predominantly of left bundle
      branch block. When left ventricular (LV) conduction delay is superimposed upon
      ventricular dysfunction, it appears to be a marker of disease severity. These
      conduction abnormalities have deleterious effects both on systolic function and
      LV filling, and they can induce or enhance mitral functional regurgitation. CRT
      attempts to correct the deleterious effect of dysynchrony by increasing LV
      filling time, decreasing septal dyskinesis and reducing mitral regurgitation.
      Several observational studies and randomized, controlled trials have shown the
      benefit of CRT in a subgroup of patients with heart failure, with conduction
      delays. Improvements were found in the mean distance walked in 6 minutes, quality
      of life (QOL), NYHA functional class, in peak oxygen uptake (V-dot(2)), total
      exercise time, reduction of hospitalization, LV function and reduction of the LV
      end-diastolic diameter. These studies support the therapeutic value of
      ventricular resynchronization in patients with severe heart failure, who have
      intraventricular conduction delay but who do not have a standard indication for
      the implantation of a pacemaker. In respect to these study results, possible
      indications for a biventricular pacing device at this time are as follows: NYHA
      functional class III, LV ejection fraction <35%, sinus rhythm, QRS duration >150
      msec and drug refractory despite individual optimal heart failure therapy. CRT
      significantly improved symptoms, exercise tolerance and QOL in most patients.
      However, further studies are needed to assess long-term clinical effects and
      prognosis, as well as economic benefit of this therapeutic approach.

PMID- 14727968
TI  - New targets for antithrombotic drugs.
AB  - The normal hemostatic process is initiated by disruption in the vascular
      continuity and exposure of the subendothelial components. Platelets adhere to
      subendothelium-bound von Willebrand factor via glycoprotein (GP) Ib complex. This
      initial interaction per se and the release of platelet agonists transduce signals
      that lead to the rise in intracellular Ca(2+). The rise in Ca(2+) induces shape
      change, prostaglandin synthesis, release of granular contents and conformational
      changes in platelet Gp IIb-IIIa. Gp IIb-IIIa in activated platelets becomes
      competent to bind fibrinogen and other adhesive proteins and mediates platelet
      cohesion (primary hemostatic plug). Furthermore, the activated platelet surface
      provides an efficient catalytic surface for the coagulation reactions, ultimately
      resulting in the formation of fibrin (secondary hemostasis). Normally the
      hemostatic process plays a delicate balance between keeping the blood in the
      fluid state to maintain flow and rapidly forming an occluding plug following
      vessel injury. Thrombosis occurs because of alteration in this delicate balance.
      Consequences of thrombosis are a major cause of morbidity and mortality in
      industrialized countries. Arterial thrombosis occurs in the setting of previous
      vessel wall injury mostly because of atherosclerosis, while venous thrombosis
      occurs in areas of stasis. The recent advances in our understanding of the
      hemostatic process have led to a better elucidation of the mechanism of action of
      many antithrombotic drugs and identification of new targets for drug development.
      The molecular target of the well known antiplatelet drug ticlopidine has been
      identified. Large numbers of IIb-IIIa inhibitors have been developed based on the
      crystal structure of a potent antagonist echistatin. The mechanism of action of
      heparin has been defined at the molecular level. As a result a synthetic
      pentasaccharide, based on antithrombin-binding domain of heparin, has been
      developed and tested successfully in clinical trials. New generation direct
      thrombin inhibitors are being developed based on the crystal structure of
      thrombin. Factor Xa has a critical position at the convergence of intrinsic and
      extrinsic pathway ways. The clinical tolerability and the efficacy of low
      molecular weight heparins led to the concept that inhibition of further thrombin
      generation, by blocking factor Xa alone, can be an effective way of preventing
      thrombus growth without inactivating thrombin. A large number of specific factor
      Xa inhibitors are under development. Some of these drugs have already undergone
      preliminary clinical trials and appear to be promising. Future clinical trials
      will determine whether these new drugs will provide better risk-benefit ratio in
      treatment of thrombotic disorders.

PMID- 14727969
TI  - Current management of unstable angina: lessons from the TACTICS-TIMI 18 trial.
AB  - Patients presenting with unstable angina pectoris or non-Q-wave myocardial
      infarction (MI), if treated inadequately, are at a high risk of MI and subsequent
      mortality. The use of intravenous small molecule glycoprotein IIb/IIIa inhibitors
      along with standard therapeutic management options improves outcome. Since the
      publication of the Thrombolysis in Myocardial Ischemia IIIB, Veterans Affairs Non
      Q-Wave Infarction Strategies In-Hospital (VANQWISH) and Fragmin and Fast
      Revascularization during InStability in Coronary artery disease II (FRISC II)
      studies, there is great debate about the advantages of following an early
      'invasive' treatment option with coronary angiography and revascularization after
      initial medical therapy compared with the 'conservative' approach, where
      angiography is reserved for those who remain symptomatic. The Treat angina with
      Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy
      -Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI 18) study has helped to
      resolve some of the controversies since it was designed with more current medical
      (early and routine use of tirofiban) and revascularization (use of stents during
      percutaneous coronary interventions) options as part of the invasive treatment
      protocol. This study indicated that an early invasive strategy in risk stratified
      patients combined with early use of tirofiban with standard medical therapy
      significantly improves outcome and appears well tolerated.

PMID- 14727970
TI  - Pharmacotherapy of obesity: currently marketed and upcoming agents.
AB  - In many industrialized nations, obesity is now considered an epidemic, resulting
      in accelerated morbidity and mortality. Obesity is associated with an increased
      risk of coronary artery disease as well as the metabolic syndrome comprising
      abdominal obesity, increased fasting blood glucose levels, dyslipidemia and
      hypertension, which are all recognized cardiovascular risk factors. Diet,
      exercise, and lifestyle changes constitute important recommendations for
      treatment. Unfortunately, although effective in some individuals, these
      recommendations have proven to be ineffective in adequately addressing the broad,
      enlarging scope of this public health problem. Drug treatment is often indicated
      but is somewhat limited by the minimal number of well tolerated drugs that have
      proven to have long-term efficacy in maintaining bodyweight loss. For example,
      phentermine may result in modest bodyweight loss through suppression of appetite,
      but potential cardiovascular adverse effects exist and the efficacy is mainly
      short-term. Sibutramine, an inhibitor of serotonin and norepinephrine
      (noradrenaline) reuptake, may increase satiety and result in modest bodyweight
      loss. However, cardiovascular adverse effects may occur in susceptible patients.
      Nonetheless, sibutramine is one of the few drugs that has been approved by the US
      Food and Drug Administration (FDA) for bodyweight loss. Orlistat, a lipase
      inhibitor, is also approved by the FDA for bodyweight loss but may have
      bothersome gastrointestinal adverse effects, especially among patients who do not
      adhere to the recommended low-fat diet. Ongoing studies continue to evaluate
      other drug treatments that may result in bodyweight reduction through a number of
      different mechanisms. It is anticipated that the development of effective and
      well tolerated antiobesity drugs will elevate the pharmacologic treatment of
      obesity to the status of other cardiovascular risk factors and metabolic
      disorders. This may be especially important given that dyslipidemia, hypertension
      and type 2 diabetes mellitus are often secondary to, or exacerbated by, obesity.

PMID- 14727971
TI  - Transmyocardial laser revascularization: a review of basic and clinical aspects.
AB  - Transmyocardial laser revascularization (TMR or TMLR) is a surgical therapy
      developed to treat patients with debilitating, medically refractory angina
      pectoris due to epicardial coronary artery disease that is not amenable to
      treatment using the traditional methods of percutaneous coronary intervention
      (PCI) or coronary artery bypass graft surgery (CABG). This technique can also be
      applied percutaneously [percutaneous myocardial revascularization (PMR) or direct
      myocardial revascularization (DMR)]. The original hypotheses which motivated
      development of TMR were that: (i) oxygenated blood could flow directly from the
      left ventricle and perfuse the myocardium; and (ii) such artificially created
      channels would remain patent. However, experimental data have refuted both
      hypotheses. In the face of early reports of marked clinical benefits in terms of
      relief of anginal symptoms, alternate hypotheses to explain the mechanism have
      been pursued, including TMR-associated neoangiogenesis and cardiac denervation.
      Clinically, numerous reports of reduction in frequency and severity of anginal
      symptoms, improved exercise tolerance and improved quality of life have appeared
      from nonblind registry-type studies as well as nonblind randomized clinical
      trials of TMR or PMR versus continued medical therapy. TMR was not associated
      with a significant improvement in survival compared with medical therapy alone in
      randomized trials. For example, the prospective, randomized Angina Treatments
      Lasers and Normal Therapies in Comparison (ATLANTIC) trial found a 1-year
      mortality of 5% in 92 TMR-treated patients and 10% in 90 patients treated with
      medication only. No proof of improved myocardial blood flow in hearts of treated
      patients is currently available. The first randomized study of PMR was the
      Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial
      which found significantly greater improvements in anginal symptoms and exercise
      tolerance with PMR plus medical therapy, compared with medical therapy alone. The
      preliminary results of two double-blind studies with PMR/DMR have been presented
      but have not yet been published in full. Whereas PMR-treated patients did
      significantly better than sham-treated control groups after 6 months in the
      Blinded Evaluation of Laser Intervention Electively For angina pectoris (BELIEF)
      trial, there was no difference after 1 year between DMR-treated patients and
      those treated with medication only in the DMR In Regeneration of Endomyocardial
      Channels Trial (DIRECT). Different devices used for revascularization in these
      two trials may explain the disparity in the results, and therefore the efficacy
      and tolerability of each device should be judged upon data collected with that
      particular device.

PMID- 14727972
TI  - Valsartan: in chronic heart failure.
AB  - Valsartan, an orally active nonpeptide angiotensin II (AII) receptor antagonist
      with selectivity for the AII type I (AT(1)) receptor subtype, has recently been
      approved by the US Food and Drug Administration for the treatment of patients
      with heart failure (New York Health Association class II-IV) who are intolerant
      of ACE-inhibitor therapy. Results from the Valsartan Heart Failure Trial (Val
      HeFT) showed that in patients with chronic heart failure (CHF) [n = 5010],
      valsartan 160 mg twice daily, when used in combination with conventional therapy
      for heart failure, reduced the risk of the combined endpoint of mortality and
      morbidity by 13.2% compared with placebo. However, there was no significant
      difference in overall mortality between the valsartan and placebo groups.
      Morbidity was defined as cardiac arrest with resuscitation, hospitalization for
      heart failure, or administration of intravenous inotropic or vasodilator drugs
      for > or =4 hours without hospitalization. Among patients not receiving an ACE
      inhibitor, irrespective of concomitant beta-blocker use, valsartan reduced the
      risk of mortality and the combined endpoint by 33.1% and 44% compared with
      placebo; total hospitalizations for heart failure were also significantly lower
      in the valsartan group (27.6 vs 64.6%). In the subgroup of patients who were
      taking an ACE inhibitor and a beta-blocker at baseline (n = 1610), mortality was
      significantly higher in the valsartan group than in the placebo group. The most
      common adverse events in the valsartan and placebo groups which led to
      discontinuation of treatment were dizziness, renal impairment (both of which
      occurred in significantly more valsartan recipients) and hypotension.

PMID- 14727976
TI  - Can angiotensin receptor antagonists prevent restenosis after stent placement?
AB  - Restenosis rates after coronary stent implantation in complex lesions are between
      30 and 50%. Neointimal hyperplasia promoted by complex interaction between
      cellular and acellular elements, such as cytokines and growth factors, is thought
      to be the primary process responsible for restenosis. The risk of in-stent
      restenosis is increased in patients with a history of restenosis after
      percutaneous transluminal coronary angioplasty, in long lesions, in total
      occlusions, in patients with diabetes mellitus, in small vessels, in the proximal
      parts of the left anterior descending coronary artery and in cases of stent
      oversizing. In-stent restenosis represents a serious economic burden on society
      because treatment strategies include expensive approaches such as cutting-balloon
      angioplasty, rotational atherectomy and brachytherapy. A number of
      pharmacological agents, including ACE inhibitors, have been unsuccessful in
      preventing restenosis. Alternative procedures such as brachytherapy, radioactive
      stents and drug-eluting stents are under evaluation. Although sirolimus- or
      paclitaxel-eluting stents have been associated with very low restenosis rates
      over durations of 6 to 12 months, the long-term efficacy and tolerability of this
      approach is currently being investigated. Although ACE inhibitors have failed in
      reducing restenosis rates, the selective angiotensin II type 1 (AT(1)) receptor
      antagonist valsartan has shown encouraging results in the single-center Valsartan
      for Prevention of Restenosis after Stenting of Type B2/C lesions trial
      (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study
      to have evaluated the effect of an angiotensin receptor antagonist on in-stent
      restenosis in a moderate number of patients. Compared with ACE inhibitors,
      angiotensin receptor blockers exert additional effects on the pathophysiological
      processes which lead to restenosis. Angiotensin receptor antagonists may affect
      several mechanisms involved in neointimal hyperplasia such as decreasing
      circulating cytokine and growth factor levels and reducing neutrophil activation,
      especially after stenting in acute coronary syndromes, but the results need to be
      confirmed in a large multicenter trial. The question whether long-term therapy,
      with an oral angiotensin receptor antagonist, is cost-effective and whether
      angiotensin receptor antagonists should be used as an add-on therapy to drug
      eluting stents, requires clarification.

PMID- 14727977
TI  - Effects of the thiazolidinediones on cardiovascular risk factors.
AB  - Rosiglitazone and pioglitazone are medications from the thiazolidinedione class
      of compounds currently available for the treatment of type 2 diabetes mellitus.
      Traditionally used to enhance insulin sensitivity and decrease plasma insulin
      levels, added applications have emerged beyond those involving glycemic control.
      Cardiovascular risk factors associated with insulin resistance such as elevated
      blood pressure, dyslipidemia, abnormal fibrinolysis, and endothelial and vascular
      dysfunction have been shown to improve after thiazolidinedione treatment. Therapy
      with rosiglitazone or pioglitazone has been found to modify vascular reactivity
      and other processes involved in atherosclerosis. There may be differences between
      the agents in their effects on plasma lipid characteristics and particle size.
      These agents serve as excellent adjuncts to oral and insulin therapy for patients
      with type 2 diabetes mellitus and hold promise for the prevention of
      cardiovascular disease associated with the insulin resistance syndrome. Clinical
      trials are in progress to determine whether such therapy will lead to a reduction
      in cardiovascular events.

PMID- 14727978
TI  - Cardiovascular risk in patients with early renal insufficiency: implications for
      the use of ACE inhibitors.
AB  - Patients with end-stage renal disease die from cardiovascular disease at a much
      younger age than people in the general population do. Here, we review the
      evidence linking early renal insufficiency (ERI) to an increased cardiovascular
      risk. A number of cardiovascular risk factors become prevalent with ERI,
      including night-time hypertension, increase in serum levels of lipoprotein (a),
      homocysteine and asymmetric dimethyl-arginine, and insulin resistance. Also, an
      epidemiologic association between coronary artery disease (CAD) and
      nephrosclerosis, a frequent cause of ERI in the elderly, is documented. In the
      middle-aged, general population ERI, found in 8% of women and 9% of men, was not
      associated with cardiovascular disease. However, in a representative sample of
      middle-aged British men the risk of stroke was 60% higher for the subgroup of
      individuals with ERI. In people at high cardiovascular risk (mostly CAD), the
      Heart Outcomes Prevention Evaluation (HOPE) study found a 2-fold (unadjusted) or
      1.4-fold (adjusted) higher incidence of cardiovascular outcomes with ERI. The
      incidence of primary outcome increased with the level of serum creatinine. At
      least four studies have determined the cardiovascular risk associated with ERI in
      hypertension. In Hypertension Detection and Follow-up Program, as in HOPE,
      cardiovascular mortality increased with higher serum creatinine levels (5-fold
      difference in cardiovascular mortality between the lowest and the highest
      creatinine strata). In patients with hypertension with low risk, the Hypertension
      Optimal Treatment and a small Italian trial found about a doubling in
      cardiovascular outcomes in ERI. However, in the Multiple Risk Factor Intervention
      Trial, not baseline serum creatinine level, but its increase on follow-up
      predicted future cardiovascular disease. These observational data suggest that
      ERI, independent of etiology, is a strong predictor of cardiovascular disease,
      present in 10% of a population at low, and up to 30% at high, cardiovascular
      risk. No prospective therapeutic trials aimed at reducing the cardiovascular
      burden in individuals with ERI are available. Subgroup analyses of the HOPE study
      indicate that ACE inhibition with ramipril is beneficial without an increased
      risk of adverse effects like acute renal failure or hyperkalemia. Thus the
      frequent practice of withholding ACE inhibitors from patients with mild renal
      insufficiency is unwarranted, especially since this identifies a group at high
      risk who appears to benefit most from treatment. In addition, there is evidence
      that ACE inhibitors improve renal outcomes in renal insufficiency. Prospective
      studies should test the predictive power of ERI for cardiovascular disease and
      therapeutic options.

PMID- 14727979
TI  - Perspectives of drug-eluting stents: the next revolution.
AB  - Coronary stent implantation has become a well established therapy in the
      management of coronary artery disease (CAD). Although the Stent Restenosis Study
      (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated
      convincingly that stenting is superior to percutaneous transluminal coronary
      angioplasty with respect to restenosis in de novo lesions, there is, however,
      still a high incidence (10 to 50%) of restenosis following stent implantation.
      Improvements in stent design and implantation techniques resulted in an increase
      in the use of coronary stents and today, in most centers in the US and Europe,
      stenting has become the predominant form of nonsurgical revascularization
      accounting for about 80% of all percutaneous coronary intervention procedures.
      Coronary stents provide luminal scaffolding that virtually eliminates elastic
      recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia
      and in fact lead to an increase in the proliferative comportment of restenosis.
      Agents that inhibit cell-cycle progression indirectly have also been tested as
      inhibitors of vascular proliferation. When coated onto stents, sirolimus, a
      macrolide antibiotic with immunosuppressive properties, and paclitaxel and
      dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth
      muscle cells (SMC) and inhibited neointimal formation in animal models.
      Preliminary clinical studies with drug-eluting stents produced dramatic results
      eliminating restenosis in large and mid-size arteries. Quantitative coronary
      angiography and intravascular ultrasound demonstrated virtually complete
      inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent
      implantation. Results are also very encouraging with paclitaxel-coated stents.
      However, it needs to be proven that current drug-eluting stents will produce
      similar results in 'real life' interventional practice (long lesions, lesions in
      small vessels, in vein grafts, chronic total occlusions, and bifurcated and
      ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx
      Velocity trade mark balloon expandable stent in the treatment of patients with de
      novo coronary artery lesions (SIRIUS) trial may answer some of these concerns.
      With further improvements, including the expansion of drug-loading capacity,
      double coatings and coatings with programmable pharmacokinetic capacity using
      advances in nanotechnology (which may allow for more precise and controlled
      release of less toxic and improved molecules), we think that in the next few
      years the practice of interventional cardiology may undergo major changes. A new
      era of dramatic improvements in the treatment of CAD may have dawned. The
      prospect of approval of this technology should herald a host of clinical trials
      to revisit basic assumptions about the place of coronary stenting in the
      contemporary care of obstructive (and nonobstructive) CAD.

PMID- 14727980
TI  - Naturoceutical agents in the management of cardiovascular disease.
AB  - During the past decade, complementary and alternative medicine (CAM) has grown in
      attractiveness to the Western public, and in recognition by practitioners of
      traditional medicine. The incorporation of effective CAM therapies into
      traditional practice is termed 'integrative medicine'. One form of CAM
      demonstrating exponential growth through mass public consumerism is the use of
      naturoceuticals. Naturoceutical (or nutraceutical) agents are defined as mega
      dose vitamins, herbal products or other 'natural' supplements purchased and
      consumed with premeditated 'pharmaceutical' intention to treat or prevent an
      illness or disease. Dietary supplements per se, are intended to supply adequate
      nutrients that may be lacking from the diet, and are thus, generally health
      promoting. A regulatory paradox exists since naturoceuticals are classified as
      dietary supplements although many possess measurable pharmacologic activity. In
      reference to cardiovascular disorders, consumers use naturoceuticals for three
      distinctly recognizable purposes. These are the primary and secondary prevention
      of cardiovascular diseases and the treatment of diagnosed disorders such as heart
      failure, angina pectoris or arrhythmia. The evidence base supporting the routine
      use of naturoceutical products for these intentions is sparse, although the
      likelihood of harm from their consumption is low for an average, healthy adult.
      Evidence of significant harm (including fatalities) has been observed when
      certain herbal products are used in excess or in combination with, other herbs or
      prescription drugs. The safety of use at the extremes of age, or by persons with
      cardiac, renal or hepatic impairment is also a concern. Healthcare professionals
      should routinely document patient naturoceutical use, be alert for and report
      suspected adverse effects. Until well-designed clinical trials determine the
      proper indication(s), dose safety profile and risk/benefit ratio for these
      products, their routine use should not be advocated. Thus, the role of
      naturoceutical agents in the integrative management of cardiovascular disorders
      remains undefined.

PMID- 14727981
TI  - Laser coronary angioplasty: history, present and future.
AB  - The efficacy of percutaneous transluminal coronary angioplasty (PTCA) is limited
      by remaining plaque tissue and the development of restenosis. It has been
      demonstrated that the restenosis rate is low if a large lumen diameter is
      achieved after coronary intervention. Debulking of coronary stenoses is a concept
      to increase the luminal diameter after intervention. Laser angioplasty debulks
      coronary stenoses by ablation of atherosclerotic plaque. Since the first
      intravascular laser intervention, the technique has been significantly improved
      by the use of optimized wavelength, the development of flexible optimally spaced
      multifiber catheters and an additional saline flush technique. These technical
      advancements allowed a reduction in the incidence of adverse events, such as the
      number of dissections and perforations, associated with the use of the laser
      technique. Coronary laser angioplasty is commonly combined with adjunctive
      balloon angioplasty to optimize the outcome. Laser coronary angioplasty was not
      followed by a lower restenosis rate compared with plain balloon angioplasty in
      lesions without stents, however, a randomized comparison of the techniques
      including the use of the saline flush technique is not available yet. The value
      of excimer (acronym for excited dimer) laser coronary angioplasty for treatment
      of in-stent restenosis is still under investigation. So far, nonrandomized single
      center studies have not suggested a relevant benefit for this technique used for
      in-stent restenosis. In nonstented lesions there remain niche indications for
      laser angioplasty such as the treatment of ostial lesions, diffuse lesions or
      lesions traversable with a guidewire but not with an angioplasty balloon. Laser
      coronary angioplasty may also be useful after a failed balloon angioplasty and in
      patients with chronic total occlusions. The potential advantages of combining
      laser coronary angioplasty with vaporization of thrombus in patients with acute
      coronary syndromes are currently under evaluation.

PMID- 14727983
TI  - Clinical potential of nonhemoglobin oxygen therapeutics in cardiac and general
      surgery.
AB  - Significant efforts have been made over the past 70 years to find a solution that
      could substitute for blood. Over the years, the focus has shifted to developing a
      solution capable of delivering oxygen to the tissues. Fluorocarbons (FC) are
      highly inert solutions with a high solubility for all gases, making them a prime
      candidate to become such an oxygen delivery agent. Although clinical research
      efforts into the use of these agents as substitutes for blood transfusions
      continue at present, the rapid disappearance of emulsified FCs from the vascular
      space and accumulation in the liver and spleen may well limit their usefulness as
      transfusion substitutes. Because of their ability to dissolve significant
      quantities of oxygen and carbon dioxide, these agents may be more attractive as
      oxygen delivery agents during periods of local or global organ ischemia,
      including preservation of organs for transplantation. FCs have also been tested
      in animal models of cardiopulmonary bypass, and may be efficacious in adsorbing
      the gases present in air emboli. Recently a second class of oxygen therapeutics
      (allosteric modifiers) has been developed, and these agents enhance oxygen
      delivery by shifting the oxygen dissociation curve to the right, thus increasing
      tissue PO(2). Allosteric modifiers have been shown to effectively shift the p50
      of hemoglobin 10mm Hg at clinically relevant dosages, and have been shown (in
      animal models) to reduce cerebral infarct size following carotid ligation and to
      improve myocardial performance following myocardial ischemia. Despite significant
      research efforts, however, none of the solutions under development are currently
      approved for clinical use by the Food and Drug Administration, with the exception
      of myocardial contrast imaging agents.

PMID- 14727984
TI  - Antihypertensive drugs: an overview.
AB  - For most patients with systemic hypertension, long-term drug treatment is
      indicated and is beneficial. There is overwhelming evidence to suggest that
      antihypertensive drugs offer protection against complications of hypertension.
      Whereas nondrug therapeutic options should be implemented in all patients, a vast
      majority will require pharmacological treatment to achieve goal blood pressure
      levels. Fortunately, a number of drugs are available to accomplish successful
      treatment of hypertensive disorders. While it is conventional to initiate
      treatment with a single drug, a suitable combination of drugs is often required
      to control the blood pressure effectively. Although diuretics and beta-blockers
      are effective and well tolerated, other classes of drugs are being increasingly
      used as the initial choice of therapy for hypertension. Every class of
      antihypertensive drugs offer advantages and some disadvantage; the physician
      should weigh the benefits and risks in selecting one drug over another. While the
      clinical parameters are followed in the management of patients with hypertension,
      it is also necessary to monitor the patients' biochemical profile periodically in
      order to modify and adjust the therapy accordingly. A careful selection of drug
      therapy along with close follow-up offers the best prospect to reduce the burden
      of morbidity and mortality in hypertension. This article provides an overview of
      drugs in the management of patients with hypertension.

PMID- 14727985
TI  - Management of protease inhibitor-associated hyperlipidemia.
AB  - Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced
      levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high
      density lipoprotein-cholesterol, has been recognized in patients with human
      immunodeficiency virus (HIV) infection. It is thought that elevated levels of
      circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha,
      may alter lipid metabolism in patients with HIV infection. Protease inhibitors,
      such as saquinavir, indinavir and ritonavir, have been found to decrease
      mortality and improve quality of life in patients with HIV infection. However,
      these drugs have been associated with a syndrome of fat redistribution, insulin
      resistance, and hyperlipidemia. Elevations in serum total cholesterol and
      triglyceride levels, along with dyslipidemia that typically occurs in patients
      with HIV infection, may predispose patients to complications such as premature
      atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia
      and hypertriglyceridemia occur in greater than 50% of protease inhibitor
      recipients after 2 years of therapy, and that the risk of developing
      hyperlipidemia increases with the duration of treatment with protease inhibitors.
      In general, treatment of hyperlipidemia should follow National Cholesterol
      Education Program guidelines; efforts should be made to modify/control coronary
      heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and
      maximize lifestyle modifications, primarily dietary intervention and exercise, in
      these patients. Where indicated, treatment usually consists of either pravastatin
      or atorvastatin for patients with elevated serum levels of LDL-C and/or total
      cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and
      triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, but it is also associated with more drug interactions
      compared with pravastatin. Simvastatin and lovastatin are significantly
      metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended
      for coadministration with protease inhibitors. A fibric acid derivative
      (gemfibrozil or fenofibrate) should be used in patients with primary
      hypertriglyceridemia. However, it must be kept in mind that protease inhibitors,
      such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of
      the fibric acid derivatives and may, therefore, reduce the lipid-lowering
      activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG
      CoA reductase inhibitors may be used in combination with fibric acid derivatives
      but patients should be carefully monitored for liver and skeletal muscle
      toxicity. Select patients may experience improvements in serum lipid levels when
      their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine,
      or abacavir; however each patient's virologic and immunologic status must be
      taken closely into consideration.

PMID- 14727986
TI  - Secondary prevention of coronary artery disease with antimicrobials: current
      status and future directions.
AB  - Over the past several decades, coronary artery disease (CAD) has become the major
      health problem in the Western world with more than 50% of deaths attributed to
      its complications. The exact causes of atherosclerosis are not clearly known,
      although multiple risk factors (e.g. hypertension, hyperlipidemia, diabetes
      mellitus, family history, and smoking) have been well described. However, these
      risk factors account for only about 50% of the total risk of CAD. Consequently,
      an ongoing search is under way to discover new risk factors for atherosclerosis
      as well as the basic underlying causes of progression. Although the evidence is
      not yet definitive, recent studies have shown that chronic infection by such
      bacterial organisms as Chlamydia pneumoniae, Helicobacter pylori, and a variety
      of dental pathogens may play a causative role in atherosclerosis. If this is
      true, then antimicrobial therapy may be helpful in the secondary prevention of
      CAD. Indeed, several small studies have already been completed testing this
      hypothesis. This article reviews the evidence associating these bacterial
      pathogens to CAD and presently available information regarding the use of
      antibiotics in the setting. At present, most studies evaluating the potential
      efficacy antimicrobials in the secondary prevention of CAD have tested the use of
      macrolide antibodies. Although several small preliminary studies have reported
      promising results favoring a clinical benefit from even short (<3 months) courses
      of antimicrobial therapy, the first large clinical trial, the Weekly Intervention
      with Zithromax for Atherosclerosis and its Related Disorders (WIZARD) study, did
      not show a statistically significant beneficial effect of a 3 month course of
      azithromycin over placebo by the end of up to 4 years follow-up. However, a
      statistically significant (p = 0.03) 33% reduction in death and myocardial
      infarction was found at 6 months, 3 months after the discontinuation of
      antibiotics. This robust clinical benefit, however, was not sustained over the
      ensuing 3.5 years of follow-up. These disappointing long-term outcomes of short
      term therapy with antimicrobials may be explained by the recently discovered
      difficulty found in eradicating chronic vascular infections such as C.
      pneumoniae. It remains possible that longer term antimicrobial therapy or short
      term use of more potent single agents or combinations, capable of effectively
      eradicating the offending organisms might provide added clinical benefit in the
      fight against CAD. Further studies are ongoing or planned to evaluate this
      potential. In the meantime, it is not presently recommended that antimicrobials
      be routinely prescribed for the secondary prevention of CAD.

PMID- 14727987
TI  - Antianginal effects of trimetazidine and left ventricular function improvement in
      patients with stable angina pectoris.
AB  - OBJECTIVE: To evaluate the effects of add-on treatment with trimetazidine, single
      dose and long-term, on clinical and objective parameters of ischemia in patients
      with stable angina pectoris receiving standard antianginal therapy. DESIGN: One
      month single-blind, placebo-controlled study. PATIENTS: 40 patients with stable
      angina pectoris. INTERVENTIONS: Patients received 1-month treatment with either
      trimetazidine 20 mg (n = 20) or placebo (n = 20) 3 times daily in addition to
      standard antianginal therapy. MAIN OUTCOME MEASURES: All patients underwent
      bicycle stress tests at baseline and at 1 month to assess exercise tolerance.
      Patients receiving trimetazidine also underwent a stress test 2 hours after
      administration of a 60 mg single dose. Influence of trimetazidine on stress
      induced left ventricular function was assessed in 11 patients, with dobutamine
      stress echocardiography performed at baseline and at 1 month. Clinical efficacy
      was evaluated in terms of mean weekly number of anginal episodes and weekly
      nitroglycerin (glyceryl trinitrate) tablet consumption during the study. RESULTS:
      Trimetazidine significantly improved most stress test parameters, after a single
      dose and after 1 month of treatment; the rate-pressure product remained
      unchanged. Dobutamine tests showed significant (p < 0.05) increases from baseline
      values in time to onset of anginal pain and threshold dobutamine dose (13.5 +/-
      0.7 versus 10.2 +/- 0.8 min, and 43.6 +/- 2.8 versus 35.4 +/- 3.4 microg/kg/min,
      respectively). The severity of anginal pain and mean weekly number of anginal
      episodes was reduced significantly (p < 0.05) from baseline values after 1
      months' treatment with trimetazidine (1.3 +/- 0.6 versus 2.3 +/- 0.3, and 6.6 +/-
      1.4 versus 10.1 +/- 1.3, respectively). After 1 month, weekly consumption of
      nitroglycerin tablets was decreased by 3.1 from baseline values in the
      trimetazidine group but increased by 0.3 in the placebo-treated group. No patient
      withdrew due to treatment-related adverse effects. CONCLUSION: This study
      confirms the antianginal and anti-ischemic efficacy of single dose and long-term
      treatment with trimetazidine. Treatment with trimetazidine was well tolerated.

PMID- 14727988
TI  - Micronized fenofibrate in dyslipidemia: a focus on plasma high-density
      lipoprotein cholesterol (HDL-C) levels.
AB  - The prodrug fenofibrate, a synthetic phenoxy-isobutyric acid derivative, is
      rapidly hydrolyzed in vivo to form fenofibric acid, which alters plasma lipid
      levels by activating the peroxisome proliferator-activated receptor alpha. The
      micronized fenofibrate 200 mg capsule formulation, and the recently developed
      micronized fenofibrate 160 mg tablet formulation, are bioequivalent. Micronized
      fenofibrate 200 mg/day (capsules) increased high density lipoprotein cholesterol
      (HDL-C) levels significantly from baseline in up to 7098 patients with various
      dyslipidemias in noncomparative studies. Micronized fenofibrate 200 mg/day
      (capsules) produced significantly greater elevations in HDL-C levels than a
      variety of HMG-CoA reductase inhibitors in small, randomized, double-blind and
      nonblind studies in patients with dyslipidemia (n = 91 to 227). This formulation
      of fenofibrate and gemfibrozil produced similar increases in HDL-C levels in a
      randomized, double-blind study (n = 234). Micronized fenofibrate 160 mg once
      daily (tablet) increased HDL-C levels significantly from baseline by 10.6 to
      14.5% in patients with type IIa or IIb dyslipidemia (n = 353) in two
      noncomparative studies. Additionally, total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C) and triglyceride levels, and LDL-C to HDL-C and
      TC to HDL-C ratios were lowered significantly from baseline. The tablet and
      capsule formulations of fenofibrate were both generally well tolerated in two
      noncomparative studies in 375 or 9884 patients. In double-blind, placebo
      controlled trials in a total of 804 patients, the pooled incidences of individual
      adverse events were generally similar with fenofibrate and placebo.

PMID- 14727993
TI  - Congestive heart failure: what should be the initial therapy and why?
AB  - Left ventricular systolic dysfunction is associated with neurohormonal activation
      which contributes to progressive ventricular remodeling and worsening clinical
      heart failure. Renin-angiotensin-aldosterone and sympathetic nervous systems are
      activated, not only in patients with clinically overt heart failure, but also in
      patients with asymptomatic or minimally symptomatic left ventricular systolic
      dysfunction. Activation of the angiotensin and adrenergic systems produces
      deleterious effects on systemic and coronary hemodynamics, promotes myocyte
      hypertrophy and fibroblast growth, and myocyte necrosis and apoptosis. Thus,
      therapy of heart failure should consist of pharmacologic agents not only to
      relieve symptoms but also to prevent and attenuate ventricular remodeling and
      progressive heart failure, thereby improving prognosis. In patients who are
      symptomatic, ACE inhibitors along with digitalis and diuretics as initial therapy
      (triple therapy) have the greater potential to improve exercise tolerance and
      decrease the incidence of treatment failure compared with diuretics alone or a
      combination of diuretics and digitalis. Diuretics alone should not be considered
      for long-term therapy as plasma renin activity, angiotensin II, aldosterone,
      norepinephrine and vasopressin levels may increase. ACE inhibitors decrease
      mortality in patients with heart failure resulting from left ventricular systolic
      dysfunction. The results of presently available studies indicate that angiotensin
      II receptor blockers (ARBs) do not provide any advantage over ACE inhibitors
      regarding survival benefit but may be better tolerated. Long-term adrenergic
      inhibition with the use of ss-adrenoceptor antagonists added to ACE inhibitors is
      associated with attenuation of ventricular remodeling, improvement in ventricular
      function and clinical class and survival of patients with symptomatic systolic
      left ventricular failure. Thus, initial pharmacotherapy for systolic heart
      failure should consist of: maximal tolerated dosages of ACE inhibitors;ARBs if
      ACE inhibitors are not tolerated because of intractable cough or
      angioedema;adequate dosages of hydralazine and isosorbide dinitrate if ACE
      inhibitors or ARBs are not tolerated; relatively low dosages of digoxin (serum
      concentrations of < or = 1.0 ng/dl) if not contraindicated; and diuretics to
      relieve congestive symptoms. Addition of spironolactone to ACE inhibitors can
      result in a significant reduction in the risk of sudden death in patients with
      symptomatic severe heart failure. Myocardial infarction resulting from ischemic
      heart disease is the most common cause of systolic left ventricular failure and
      the therapeutic modalities with potential to reduce the risks of myocardial
      infraction, such as risk factor modification, adequate control of diabetes and
      hypertension, antiplatelet agents and lipid-lowering agents, should also be
      included in the initial therapy.

PMID- 14727994
TI  - How do HMG-CoA reductase inhibitors prevent stroke?
AB  - Stroke is a heterogeneous disorder with significantly high morbidity and
      mortality. The relationship between serum cholesterol level and the incidence of
      stroke remains controversial. Recent evidence from primary and secondary
      prevention trials suggests that treatment with hydroxymethylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors may reduce the incidence of stroke in patients
      with coronary artery disease (CAD). In this review, we attempt to outline and
      describe the potential mechanisms of HMG-CoA reductase inhibitors in the
      prevention of stroke. In addition to their lipid-lowering action HMG-CoA
      reductase inhibitors appear to exert their beneficial effects by various nonlipid
      lowering mechanisms including anti-inflammatory effects, effect on endothelial
      function and coagulation cascade. Treatment with HMG-CoA reductase inhibitors is
      associated with decreased progression, plaque stablization and even regression of
      atheromatous plaque in the carotid arteries. HMG-CoA reductase inhibitors also
      inhibit the coagulation cascade at various levels such as activation of
      prothrombin, factor V, factor X and liberation of tissue factor in response to
      vascular injury. Inhibition of fibrinolysis occurs secondary to inhibition of
      plasmin generation. Pravastatin therapy is associated with a reduction in the
      size of aortic atheroma which is an independent risk factor for stroke. Lastly,
      left ventricular dysfunction after acute myocardial infarction is associated with
      an increased risk of stroke and HMG-CoA reductase inhibitors may indirectly
      decrease the incidence of stroke by reducing coronary events. Most of these
      effects are independent of the cholesterol-lowering effects of HMG-CoA reductase
      inhibitors. In conclusion, HMG-CoA reductase inhibitors may have a role in
      primary prevention of stroke in patients with CAD.

PMID- 14727995
TI  - Management of co-existing diabetes mellitus and dyslipidemia: defining the role
      of thiazolidinediones.
AB  - The observed reduction in macrovascular outcomes in the United Kingdom
      Progressive Diabetes Study (UKPDS) trial in patients with type 2 diabetes
      mellitus (DM), treated intensively with insulin or sulfonylureas, was of
      borderline significance (p = 0.052). This may be because of the role of factors
      other than glycemic control in the etiology of macrovascular disease. The UKPDS
      and other studies have suggested that lipid parameters are potent predictors of
      adverse outcomes in patients with type 2 DM. In patients with DM, dyslipidemia is
      characterized by elevated serum triglycerides and low high density lipoprotein
      cholesterol (HDL-C) with normal total serum cholesterol levels and usually
      accompanied by an elevation of atherogenic, small, dense low density lipoprotein
      cholesterol (LDL-C) particles. Dyslipidemia is only partly corrected by dietary
      and lifestyle modifications and pharmacological glycemic control in patients with
      DM. Several guidelines, including those published by the New Zealand Heart
      Foundation, suggest that lipid-modifying therapies are appropriate in patients
      considered to be at high or very high risk of a cardiac event. This includes
      patients with established vascular disease. Some recent studies suggest that
      patients with type 2 DM have risk comparable to patients without DM, but have
      experienced previous myocardial infarction (MI). Subgroup analysis of trials
      including the Scandinavian Simvastatin Survival Study (4S) and Cholesterol and
      Recurrent Events (CARE), which included patients with DM, have shown a
      significant reduction in adverse outcomes, although many patients with DM and
      dyslipidemia were excluded. Of lipid-lowering drugs, fibric acid derivatives are
      probably the most appropriate for patients with DM and dyslipidemia and their
      role is being evaluated in large, long-term outcome studies such as Fenofibrate
      Intervention and Event Lowering in Diabetes (FIELD). Thiazolidinediones, a new
      class of compound for treating patients with type 2 DM, primarily exert their
      glucose-lowering effect by increasing insulin sensitivity at the level of
      skeletal muscle, and to a lesser extent, at the liver by decreasing hepatic
      glucose output. Some of their actions are mediated through binding and activation
      of the peroxisome proliferator-activated receptor-gamma, a nuclear receptor that
      has a regulatory role in differentiation of cells, especially adipocytes. The
      nonhypoglycemic effects of thiazolidinediones, therefore, offer additional
      potential mechanisms for benefit in patients with type 2 DM and insulin
      resistance. Thiazolidinediones increase serum HDL-C levels. Troglitazone and
      pioglitazone have been shown to decrease serum triglyceride levels.
      Rosiglitazone, conversely has no significant effect on serum triglyceride levels.
      All of the thiazolidinediones increase serum LDL-C levels (pioglitazone to a
      lesser extent), although changes in the size of the LDL fraction may render it
      less susceptible to oxidation and, therefore, less atherogenic. A randomized
      comparative trial needs to be undertaken to determine whether true differences
      exist between the thiazolidinediones. Longer studies need to be undertaken to
      assess their effect on cardiovascular outcomes.

PMID- 14727996
TI  - Drug treatment of orthostatic hypotension because of autonomic failure or
      neurocardiogenic syncope.
AB  - Orthostatic hypotension either because of autonomic failure or neurocardiogenic
      syncope can be very incapacitating and should be treated accordingly. Drug
      therapy is frequently needed to alleviate orthostatic symptoms. The
      physiopathological basis of neurocardiogenic syncope and of autonomic failure is
      completely different and their treatment should be distinct. In the past 5 years,
      many randomized, placebo-controlled trials have shed light on the efficacy of
      specific pressor drugs. In patients with orthostatic hypotension because of
      autonomic failure, alpha-adrenoceptor agonists, and midodrine in particular, have
      been shown to increase standing blood pressure and decrease orthostatic symptoms.
      Other drugs such as octreotide, indomethacin or ergotamine have also been shown
      to elevate standing blood pressure and/or orthostatic tolerance. Fludrocortisone
      is a well known and frequently used pressor drug but randomized controlled
      studies are needed to measure its efficacy. In patients with orthostatic
      hypotension associated with neurocardiogenic syncope, clinical trials have
      demonstrated that beta-blockers, especially beta(1)-selective agents without
      intrinsic sympathomimetic activity such as atenolol, midodrine and paroxetine can
      decrease recurrence of syncope. Treatment algorithms, such as those presented in
      this review, should always be interpreted in the light of individual patient
      characteristics. Many of the drugs used for orthostatic hypotension have multiple
      indications and contraindications that should influence therapeutic decisions.
      Little is known about the effectiveness and tolerability of specific combinations
      of pressor drugs. Consequently, sound clinical judgment and close follow-up of
      patients should always guide combination therapy.

PMID- 14727997
TI  - Use of beta-blockers in atrial fibrillation.
AB  - Atrial fibrillation is the most common arrhythmia in the general population and
      is frequently associated with organic heart disease. beta-adrenoceptor
      antagonists (b-blockers) are very effective in preventing atrial fibrillation
      after coronary artery bypass surgery. It has been shown recently that the beta
      blocker metoprolol controlled release/extended release (CR/XL) is also effective
      in maintaining sinus rhythm after conversion of atrial fibrillation. There is
      concern that class I antiarrhythmic drugs, such as quinidine, disopyramide, and
      flecainide in particular, may increase mortality. The risk of proarrhythmia
      associated with beta-blocker treatment is very low. Therefore b-blockers, such as
      metoprolol CR/XL, may be the first line of treatment to maintain sinus rhythm,
      especially after myocardial infarction and in patients with chronic heart failure
      and in those with arterial hypertension. In patients with persistent atrial
      fibrillation, AV-nodal conduction-slowing drugs, such as calcium channel
      antagonists and beta-blockers are used to control the ventricular rate during
      atrial fibrillation. Several studies clearly show that beta-blockers alone, or in
      combination with digoxin are very effective in controlling the ventricular rate
      at rest and during exercise. beta-blockers are effective in maintaining sinus
      rhythm and controlling the ventricular rate during atrial fibrillation. Given
      these effects and their favorable effects on mortality, beta-blockers should be
      considered as first-line agents in the management of patients with atrial
      fibrillation.

PMID- 14727998
TI  - Apoptosis and heart failure: mechanisms and therapeutic implications.
AB  - A large volume of experimental data supports the presence of apoptosis in failing
      hearts. Apoptosis in many types of cells results from exposure to cytotoxic
      cytokines or damaging agents. Cytotoxic cytokines such as tumor necrosis factor
      (TNF)-alpha or Fas ligand (FasL) bind to their receptors to activate caspase-8,
      while damaging agents can cause mitochondrial release of cytochrome c, which can
      initiate activation of caspase-9. Caspase-8 or -9 can activate a cascade of
      caspases. The p53 protein is often required for damaging agent-induced apoptosis.
      An imbalance of proapoptotic factors versus prosurvival factors in the bcl-2
      family precedes the activation of caspases. Given these typical changes of
      apoptosis found in many cell types, the apoptotic pathway in cardiomyocytes is
      somewhat unconventional since in vivo experimental data reveal that apoptosis
      does not appear to be controlled by TNF-alpha, FasL, p53 or decrease of bcl-2. In
      vitro and in vivo studies suggest the importance of mitochondria and activation
      of caspases in cell death occurring in failing hearts. Oxidants, excessive nitric
      oxide, angiotensin II and catecholamines have been shown to trigger apoptotic
      death of cardiomyocytes. Eliminating these inducers reduces apoptosis and
      reverses the loss of contractile function in many cases, indicating the
      feasibility of the pharmacological application of antioxidants, nitric oxide
      synthetase inhibitors, ACE inhibitors, angiotensin II receptor antagonists and
      adrenergic receptor antagonists. Most inducers of apoptosis initiate a cascade of
      signaling events, including activation of the p38 mitogen-activated protein
      kinase. Small molecule inhibitors of p38 have been shown to be capable of
      preventing apoptosis and loss of contractile function associated with ischemia
      and reperfusion. Although further experimental work is needed, several studies
      have already indicated the beneficial effect of caspase inhibitors against cell
      loss and features of heart failure in vitro and in vivo. These studies indicate
      the importance of inhibiting apoptosis in therapeutic interventions against heart
      failure.

PMID- 14728000
TI  - Pluripotential mechanisms of cardioprotection with HMG-CoA reductase inhibitor
      therapy.
AB  - Treatment with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      has been accompanied by a reduced risk of cardiovascular events. Rapid onset of
      clinical benefit and weak correlations between plasma low density lipoprotein
      cholesterol levels and coronary lumen change or cardiovascular events indicates
      that nonlipid mechanisms are involved in this beneficial effects with HMG-CoA
      reductase inhibitors. Furthermore, more rapid onset of clinical benefit with HMG
      CoA reductase inhibitors in patients with acute coronary syndromes or acute
      myocardial infarction than in those with stable coronary heart disease suggest
      that HMG-CoA reductase inhibitors facilitate repair of ruptured or ulcerated
      atherosclerotic plaque, facilitate plaque stabilization and/or reduce thrombus
      formation on ruptured plaques. Treatment with HMG-CoA reductase inhibitors
      improved endothelial dysfunction in patients with hypercholesterolemia and this
      improvement in endothelial function was not correlated with reduction in total
      serum cholesterol levels. Similarly, reduction in endothelial pre-proendothelin
      mRNA expression and endothelin synthesis and blood pressure lowering with HMG-CoA
      reductase inhibitors occurred independent of lipid-lowering. Finally, HMG-CoA
      reductase inhibitors increased endothelial nitric oxide levels i.e. upregulated
      endothelial nitric oxide synthetase expression via post-transcriptional
      mechanisms and prevented its down-regulation by oxidized LDL-C. HMG-CoA reductase
      inhibitors have been shown to modulate the immune response by inhibiting
      activation of immune-competent cells such as macrophages, and antigen
      presentation to macrophages by T cells. Treatment with HMG-CoA reductase
      inhibitors can reduce expression, production and circulating levels of chemokines
      (monocyte chemoattractant protein-1) and proinflammatory cytokines [tumor
      necrosis factoralpha, interleukin (IL)-6 and IL-1beta]. HMG-CoA reductase
      inhibitors reduced inflammation in human atheroma: significantly fewer
      macrophages and T cells, less oxidized LDL-C and higher collagen content. In
      addition, treatment with HMG-CoA reductase inhibitor led to decreased cell death
      within the atheroma. Treatment with these agents also reduced expression of
      inducible cellular adhesion molecules, decreased secretion of metalloproteinases
      by macrophages, reduced vascular smooth muscle cell apoptosis. Lastly, HMG-CoA
      reductase inhibitors appear to have important effects on the thrombogenesis:
      reduced expression of tissue factor production and activity; increased production
      of tissue factor package inhibitor; decreased platelet thrombus formation and
      improved fibrinolysis as a result of lowered plasminogen activator inhibitor-1
      levels. As the pluripotential cardioprotective mechanisms of HMG-CoA reductase
      inhibitors are further elucidated, it is envisaged that treatment with HMG-CoA
      reductase inhibitors will be initiated earlier and more frequently in patients
      with hypercholesterolemia.

PMID- 14728001
TI  - Oral glycoprotein IIb/IIIa inhibitors: why don't they work?
AB  - Despite their promise as orally active potent inhibitors of platelet aggregation,
      the oral platelet glycoprotein IIb/IIIa inhibitors have failed to provide a
      reduction in late ischemic events. In fact, with five large-scale randomized
      trials now complete, including over 42 000 patients, these agents have been
      associated with a surprising, yet consistent, excess in mortality. Peculiarly,
      this fatality risk has occurred in the absence of a commensurate increase in
      other ischemic end-points. While these findings have curtailed the further
      clinical development of this class of potent platelet inhibitors, the obvious
      dissociation between platelet suppression and adverse outcome requires further
      clarification. Multiple putative explanations for this excess in ischemic events
      with oral glycoprotein IIb/IIIa inhibitors have been proposed, but definitive
      data implicating a specific mechanism are currently not available. While the lack
      of concurrent aspirin may account for some of this effect, it is unlikely to
      fully explain the mortality excess. Potential mechanisms include partial agonist
      activity leading to increased expression of platelet-leukocyte adhesion
      molecules, sub-optimal inhibition of platelet aggregation, genetic polymorphisms,
      especially phospholipase A(2) polymorphism, and promotion of cardiac myocyte
      apoptosis via activation of caspase 3. Definitive elucidation of these adverse
      mechanisms will be required if further clinical development of the oral platelet
      glycoprotein IIb/IIIa inhibitors is to be pursued.

PMID- 14728002
TI  - Drugs for the prevention and treatment of thrombosis in patients with heparin
      induced thrombocytopenia.
AB  - Most patients with heparin-induced thrombocytopenia (HIT), a serious adverse
      effect of heparin mediated by platelet-activating heparin-dependent antibodies,
      require alternative anticoagulation. This is because HIT is highly prothrombotic
      and is characterized by markedly increased thrombin generation. Unfractionated
      heparins seem to induce HIT more often than low molecular weight heparins. There
      are three anticoagulants for which there is an emerging consensus for their
      efficacy in management of HIT, and which are currently approved for treatment of
      HIT in several countries: the recombinant hirudin, lepirudin, a direct thrombin
      inhibitor; the synthetic direct thrombin inhibitor, argatroban; and the
      heparinoid, danaparoid sodium, mainly exhibiting antifactor-Xa activity.
      Recommendations for optimal use of these drugs in HIT are given in this review
      stressing the need for immediate treatment of patients with HIT without awaiting
      laboratory diagnosis. Hirudin, the drug for which most data from prospective
      trials exists, can be safely and effectively used in patients with HIT, its
      dramatically increased elimination half-life in patients with renal failure being
      the most important drawback. Argatroban, which is mainly eliminated by the liver,
      could be used preferentially in such patients with renal impairment. Interference
      with the international normalized ratio makes oral anticoagulation, which is
      necessary in many patients with HIT, problematic. Activated partial
      thromboplastin time is sufficient to monitor lepirudin and argatroban treatment
      in most cases. Danaparoid sodium, with an antifactor-X activity half-life of
      about 24 hours seems to be best suited for thrombosis prophylaxis in patients
      with HIT. In some patients monitoring by determining antifactor-Xa activity is
      necessary. No antidote is available for any of the drugs discussed, and bleeding
      complications are the most important adverse effects. In situations such as
      hemodialysis or cardiopulmonary bypass, not only the characteristics of the drug
      in use itself, but also availability of monitoring methods play an important
      role. Adjunctive treatments have not been systematically evaluated and should be
      used cautiously. Recent data suggest that re-exposure of patients with a history
      of HIT with heparin, for example during cardiopulmonary bypass, can be well
      tolerated provided no circulating HIT antibodies are detectable at the time of re
      exposure, and heparin is strictly avoided pre- and postoperatively.

PMID- 14728003
TI  - Contemporary management of children with atrial septal defects: a focus on
      transcatheter closure.
AB  - Atrial septal defects that result in right atrial and ventricular volume overload
      should be closed if diagnosed in children and adolescents. With closure of the
      atrial septal defect, the left-to-right shunt is eliminated e.g. the volume
      loading of the right heart, the excessive pulmonary blood flow and the total
      cardiac work load are reduced. The possibility of future arrhythmic events is
      lessened and paradoxical emboli across the septum eliminated. The first
      intracardiac surgical repair of a congenital lesion was a defect in the atrial
      septum nearly 50 years ago. Surgical closure remains a valuable, although viable
      technique. Recently percutaneous transcatheter techniques are now available. The
      conventional approach is via a median sternotomy incision but is associated with
      pain, risk of wound infection, postoperative immobilization and a permanent scar.
      It has been suggested that alternative approaches such as surgical repair using
      mini-sternotomy or lateral thoracotomy incisions yield similar results to the
      conventional surgical technique and are associated with fewer adverse effects.
      Transcatheter closure has developed over the last two decades and has evolved
      into a well tolerated, efficient and cost effective method with minimal
      discomfort for the patients. Complete closure rates are high and this approach
      has become a viable option for ASD management.

PMID- 14728004
TI  - Hypertriglyceridemia: associated risks and effect of drug treatment.
AB  - Accumulating evidence indicates that hypertriglyceridemia (HTG) is a risk factor
      for cardiovascular disease. This increased risk is probably substantially
      mediated through the metabolic interrelationships between serum triglyceride (TG)
      levels and other risk factors, such as the atherogenic lipid profile (low high
      density lipoprotein-cholesterol levels and elevated small dense low density
      lipoprotein levels), insulin resistance, a prothrombotic propensity and low grade
      systemic inflammation. TG-lowering strategy in patients with HTG encompasses
      dietary modification and pharmacological agents, such as fibric acid derivatives,
      fish-oil and hydroxymethylglutaryl coenzyme A reductase inhibitors, which have,
      besides their known effects on the atherogenic lipid profile, beneficial effects
      on other determinants of cardiovascular disease. However, in spite of data from
      trials investigating fibric acid derivative-induced reduction in coronary events
      in patients with distinct types of hyperlipidemia, no specific trials have been
      performed that investigated this risk reduction in patients with HTG, in whom
      other cardiovascular risk factors are clustered as well. Small-scale studies on
      determinants of cardiovascular disease in patients with HTG and post-hoc analyses
      of the Helsinki Heart, Veterans Affairs High-Density Lipoprotein Cholesterol
      Intervention Trial and Bezafibrate Infarction Prevention trials in patients with
      high serum TG levels suggest a drug-induced reduction in cardiovascular events.
      However, a specific trial should be conducted to investigate the effects of lipid
      lowering therapy on clinical end-points in patients with HTG of defined types.

PMID- 14728005
TI  - Clopidogrel: potential in the prevention of cardiovascular events in patients
      with acute coronary syndromes.
AB  - Clopidogrel is a selective inhibitor of ADP-induced platelet aggregation. A
      large, multicenter, randomized study in 12 562 patients with acute coronary
      syndromes without ST-segment elevation demonstrated that treatment with
      clopidogrel (loading dose of 300 mg followed by once daily treatment with 75 mg)
      in addition to standard therapy including aspirin (75 to 325 mg/day)
      significantly reduced the risk of the combined endpoint of cardiovascular death,
      myocardial infarction or stroke compared with treatment with standard therapy.
      Furthermore, the composite risk of these outcomes or refractory ischemia was also
      significantly reduced in patients treated with clopidogrel plus aspirin. The
      effects of clopidogrel were independent of background treatment with
      cardiovascular medications and/or interventions. The risk of severe ischemia,
      recurrent angina or heart failure was also significantly reduced in patients
      receiving clopidogrel plus aspirin. There was also a significant reduction in the
      need for coronary revascularization during the initial period of hospitalization.
      In patients undergoing percutaneous coronary intervention (PCI), the relative
      risk of the combined endpoint of cardiovascular death, myocardial infarction or
      urgent target-vessel revascularization within 30 days of the intervention was
      significantly reduced. Moreover, the relative risk of the single endpoint of
      myocardial infarction within 30 days of PCI was significantly in favor of
      clopidogrel-treated patients. Hemorrhagic events (both major and minor) were
      significantly more frequent in patients with acute coronary syndromes receiving
      treatment with clopidogrel plus aspirin than in patients treated with aspirin
      alone. This was largely attributable to an increased incidence in the rate of
      gastrointestinal hemorrhage and bleeding at the site of arterial puncture.
      However, there was no difference between the two groups in the incidence of
      bleeding episodes that were considered to be life-threatening.

PMID- 14728009
TI  - Enoxaparin: in the prevention of venous thromboembolism in medical patients.
AB  - Enoxaparin (enoxaparin sodium) is a low-molecular-weight heparin that binds to
      and increases the activity of antithrombin III. The resulting complex inhibits
      prothrombinase-mediated thrombin generation and direct thrombin generation by
      binding to factor Xa and thrombin factor IIa. Enoxaparin, used as prophylaxis in
      medically ill patients at increased risk for thromboembolism, has shown
      significantly increased efficacy compared with placebo in reducing the incidence
      of deep vein thrombosis and pulmonary embolism. Indeed, 291 patients receiving
      subcutaneous enoxaparin 40 mg/day had a frequency of venous thromboembolism of
      5.5% during 14 days of treatment, whereas 14.9% of the 288 placebo recipients
      experienced thromboemboli (p < 0.001). There was no reduction in the incidence of
      thromboembolism in the 287 recipients of enoxaparin 20 mg/day (15%). In other
      studies, prophylactic treatment for 7 days with subcutaneous enoxaparin 40 mg/day
      was at least as effective as unfractionated heparin in reducing the frequency of
      venous thromboembolism in 959 nonsurgical patients at increased risk for deep
      vein thrombosis and pulmonary embolism (total incidence = 0.2 and 1.4%,
      respectively). Moreover, enoxaparin recipients experienced fewer adverse events
      than did heparin recipients. The most frequent adverse events reported in
      medically ill and surgical patients receiving enoxaparin 40 mg/day were
      hemorrhage (17.4 vs 14.3% for placebo), hematoma at injection site, anemia,
      fever, peripheral edema, nausea, ecchymosis and edema (unspecified site).

PMID- 14728013
TI  - Antiatherosclerotic effects of ACE inhibitors: where are we now?
AB  - ACE inhibitors have been used extensively in the management of patients with
      hypertension and heart failure. Over the past decade, a large body of evidence
      has emerged indicating that ACE inhibition also favorably affects the
      vasculature, and that these effects are associated with improved patient
      outcomes. Such evidence is provided by several sources: (i) experimental studies,
      which demonstrate that in addition to blood pressure lowering, ACE inhibitors
      improve endothelial function and have a host of other beneficial effects on the
      arterial wall; (ii) epidemiologic studies, which link the renin-angiotensin
      aldosterone system to increased risk for myocardial infarction, and (iii)
      clinical trials, which demonstrate that treatment with these agents reduces the
      risk for acute ischemic events, improves the function of the arterial endothelium
      and can retard the progression of the anatomic extent of atherosclerosis.

PMID- 14728014
TI  - Centrally acting imidazoline I1-receptor agonists: do they have a place in the
      management of hypertension?
AB  - Centrally acting imidazoline I(1)-receptor agonists such as moxonidine and
      rilmenidine induce peripheral sympathoinhibition via the stimulation of
      hypothetical I(1)-receptors in the rostral ventrolateral medulla. Because of a
      rather weak affinity for alpha(2)-adrenoceptors, the use of these agents is
      associated with a lower incidence of adverse reactions, such as sedation and dry
      mouth, compared with classic centrally acting alpha(2)-adrenoceptor agonists
      (clonidine, guanfacine, methyldopa). The antihypertensive efficacy of moxonidine
      and rilmenidine is well documented, and they display a favorable hemodynamic
      profile. Their tolerability is better than that of the aforementioned centrally
      acting antihypertensive agents. However, long-term outcome data for moxonidine
      and rilmenidine are not available, and neither is a quantitative evaluation of
      their adverse effects. There exists some uncertainty with respect to the identity
      of the imidazoline I(1)-receptor, which has so far not been cloned. Furthermore,
      it would be desirable to develop highly selective I(1)-receptor agonists as
      successor drugs to moxonidine and rilmenidine. Although available data indicate
      that I(1)-receptor agonists are effective in patients with hypertension,
      comparative data versus agents such as beta-blockers, diuretics, calcium channel
      antagonists and ACE inhibitors are required to establish their position in the
      treatment of hypertension. Finally, I(1)-receptor agonists have potential in the
      treatment of patients with CHF and those with the metabolic syndrome; syndrome X.

PMID- 14728015
TI  - Drug treatment of combined hyperlipidemia.
AB  - Combined hyperlipidemia is increasing in frequency and is the most common lipid
      disorder associated with obesity, insulin resistance and diabetes mellitus. It is
      associated with other features of the metabolic syndrome including hypertension,
      hyperuricemia, hyperinsulinemia and highly atherogenic subfractions of
      lipoprotein remnant particles including small dense low density lipoprotein
      cholesterol. This review examines the mechanisms by which combined hyperlipidemia
      arises and the various drugs including fibric acid derivatives,
      hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and nicotinic
      acid which can be used either as monotherapy or in combination to manage it and
      to improve prognosis from atherosclerotic disease in diabetes mellitus, insulin
      resistant states and primary combined hyperlipidemia. The therapeutic approach to
      combined hyperlipidemia involves determination of whether the cause is hepatocyte
      damage or metabolic derangements. Combined hyperlipidemia due to hepatocyte
      damage should be treated by attention to the primary cause. In the case of
      metabolic dysfunction because of imbalance in glucose and fat metabolism, therapy
      of diabetes mellitus and obesity should be optimised prior to commencement of
      lipid lowering drugs. Both fibric acid derivatives and HMG-CoA reductase
      inhibitors can be used in the treatment of combined hyperlipidemia with fibric
      acid derivatives having greater effects on triglycerides and HMG-CoA reductase
      inhibitors on LDL-C though both have effects on the other cardiovascular risk
      factors. There is some evidence of benefit with both interventions in mild
      combined hyperlipidemias and large scale trials are underway. Fibric acid
      derivatives and HMG-CoA reductase inhibitor therapy can be combined with care,
      provided that gemfibrozil is avoided, fibric acid derivatives are given in the
      mornings and shorter half -life HMG-CoA reductase inhibitors are used at night.
      Combined hyperlipidemia emergencies occur with predominant hypertriglyceridemia
      in pregnancy or as a cause of pancreatitis. Therapy in the former should aim to
      reduce chylomicron production by a low fat diet and intervention to suppress VLDL
      C secretion using omega-3 fatty acids. In the latter case, fluid therapy alone
      and medium chain plasma triglyceride infusions usually reduce levels
      satisfactorily though apheresis may be required. Blood glucose levels also need
      aggressive management in these conditions. Combined hyperlipidemia is likely to
      become an increasing problem with the increase in the prevalence of obesity and
      diabetes mellitus and needs aggressive management to reduce cardiovascular risk.

PMID- 14728016
TI  - Transfusion medicine : support of patients undergoing cardiac surgery.
AB  - There is still no alternative that is as effective or as well tolerated as blood;
      nevertheless, the search for ways to conserve, and even eliminate blood
      transfusion, continues. Based on hemoglobin levels, practice guidelines for the
      use of perioperative transfusion of red blood cells in patients undergoing
      coronary artery bypass grafting have been formulated by the National Institutes
      of Health and the American Society of Anesthesiologists. However, it has been
      argued that more physiologic indicators of adequacy of oxygen delivery should be
      used to assess the need for blood transfusion. Methods used for conserving blood
      during surgery include autologous blood donation, acute normovolemic hemodilution
      and intra- and postoperative blood recovery and reinfusion. The guidelines for
      the use of autologous blood transfusion are controversial and it does not appear
      to be cost effective compared with allogeneic blood transfusion in patients
      undergoing cardiac surgery. Similarly, the cost effectiveness of intra- and
      postoperative blood recovery and reinfusion need further evaluation. Treatment
      with recombinant human erythropoietin (rhEPO) remains unapproved in the US for
      patients undergoing cardiac or vascular surgery, but it is a valuable adjunct in
      Jehovah's Witness patients, for whom blood is unacceptable. The characterization
      of darbepoetin alfa, a novel erythropoiesis stimulating protein with a 3-fold
      greater plasma elimination half-life compared with rhEPO, is an important advance
      in this field. Darbepoetin alfa appears to be effective in treating the anemia in
      patients with renal failure or cancer and trials in patients with surgical anemia
      are planned. Desmopressin has been used to effectively reduce intraoperative
      blood loss. Topical agents to prevent blood loss, such as fibrin glue and fibrin
      gel, and agents that alter platelet function, such as aspirin (acetylsalicylic
      acid) or dipyridamole, need further evaluation in patients undergoing cardiac
      surgery. Aprotinin has been shown to preserve hemostasis and reduce allogeneic
      blood exposure to a greater extent than the antifibrinolytic agents tranexamic
      acid and aminocaproic acid. Controlled clinical trials comparing the costs of
      these agents with clinical outcomes, along with tolerability profiles in patients
      at risk for substantial perioperative bleeding are needed.

PMID- 14728017
TI  - Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and
      the incidence of CAD.
AB  - The lesions of coronary atherosclerosis represent the result of a complex,
      multicellular, inflammatory-healing response in the coronary arterial wall. In
      vivo and in vitro cellular and molecular studies have suggested a role for tissue
      homocysteine in endothelial cell injury and adverse extra-cellular matrix
      remodeling. Gene polymorphisms in relation with numerous risk factors might
      increase the incidence of coronary artery disease (CAD). In this review we have
      focused on the correlations between plasma homocysteine levels, the incidence of
      cardiovascular disease and the cytosine-to-thymidine substitution at nucleotide
      677 (C677T) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, coding
      for a key enzyme in methionine-homocysteine metabolism. The role of the C677T
      MTHFR gene polymorphism in the causation of CAD is controversial. We reviewed 12
      recent case-control studies comprising 5370 genotyped patients with CAD and 4961
      genotyped participants without CAD. There was no significant difference between
      those with and without CAD in the frequency of the C677T polymorphism (34.9 vs
      33.6%). The frequency of homozygous C677T polymorphism in these groups was 10.9
      versus 12.8%, respectively, although there were some ethnic differences in the
      C677T MTHFR polymorphism. In the analysis of the 12 studies, the odds ratio of
      CAD associated with the TT genotype (homozygous C677T polymorphism) was 1.18.
      Only slightly higher plasma homocysteine levels were observed in participants
      with the val/val (TT) genotype (14.4+/-2.9 micro mol/L in TT genotype vs 11.1+/
      1.9 and 11.9+/-2 micro mol/L in CC and CT genotype, respectively). In addition,
      the relation between homocysteine increase after methionine loading and MTHFR
      genotypes is also controversial. However, hyperhomocysteinemia because of the
      C677T MTHFR allele may be corrected with oral folic acid therapy. Further
      investigations on the relationships between MTHFR genotypes and the incidence of
      CAD should be based on larger samples, paying attention to the differences
      between various ethnic populations. Individual therapeutic strategies based on
      single nucleotide polymorphism may become increasingly important for preventive
      treatment against polygenic CAD.

PMID- 14728018
TI  - Nutritional strategy in the management of heart failure in adults.
AB  - The incidence of congestive heart failure (CHF) is increasing in Westernized
      countries, and patients with CHF experience poor quality of life (functional
      impairment, high hospitalization rate and high mortality). Malnutrition occurring
      during the course of CHF is referred to as cardiac cachexia and is associated
      with higher mortality independent of the severity of CHF. Cardiac cachexia
      involving a loss of more than 10% of lean body mass can clinically be defined as
      a bodyweight loss of 7.5% of previous dry bodyweight in a period longer than 6
      months. The energy requirements of patients with CHF, whether cachectic or not,
      are not noticeably modified since the increase in resting energy expenditure is
      compensated by a decrease in physical activity energy expenditure. Malnutrition
      in CHF has been ascribed to neurohormonal alterations, i.e. anabolic/catabolic
      imbalance and increased cytokine release. Anorexia may occur, particularly during
      acute decompensation of CHF. Function is impaired in CHF, because of exertional
      dyspnea and changes in skeletal muscle. Decreased exercise endurance seems to be
      related to decreased mitochondrial oxidative capacities and atrophy of type 1
      fibers, which are attributed to alteration in muscle perfusion and are partially
      reversible by training. Malnutrition could also impair muscle function, because
      of decreased muscle mass and strength associated with decreased glycolytic
      capacities and atrophy of type 2a and 2b fibres. With respect to the putative
      mechanisms of cardiac cachexia, anabolic therapy (hormones or nutrients) and
      anticytokine therapy have been proposed, but trials are scarce and often
      inconclusive. In surgical patients with CHF, perioperative (pre- and
      postoperative) nutritional support has been shown to be effective in reducing the
      mortality rate. Long term nutritional supplementation trials in patients with CHF
      and cachexia are thus required to establish recommendations for the nutritional
      management of patients with CHF.

PMID- 14728019
TI  - Management of acute coronary syndromes in the community hospital without cardiac
      surgical capability: how can access to interventional therapy be improved?
AB  - Early coronary artery intervention is emerging as the treatment of choice for
      patients with high risk acute coronary syndromes (ACS). However, most patients
      with ACS are admitted to hospitals which do not have ready access to
      interventional therapy. Extending the benefits of early intervention to this
      population is problematic at such community hospitals, since this approach would
      require either emergency transfer to a tertiary center or the performance of
      angioplasty on-site at hospitals without cardiac surgical capability. A third
      solution, pre-hospital ambulance triage to interventional centers, is not
      currently practised in most countries. A growing body of evidence indicates that
      hospitals without cardiac surgical capability can establish safe and effective
      primary angioplasty programs. Patients with acute myocardial infarction (AMI) who
      are randomized to transfer for primary angioplasty without fibrinolytic treatment
      have fewer major adverse cardiac events than those treated with fibrinolytics
      alone or fibrinolytics and transfer. In patients with unstable angina (UA) or non
      ST-elevation AMI, an early aggressive approach led to a significant reduction in
      the composite end-point of death, AMI, or rehospitalization for recurrent UA at 6
      months with no increase in cost, compared with conservative management. Ongoing
      trials in Europe indicate that pre-hospital ambulance triage of patients with
      large AMI to interventional centers can be remarkably rapid, safe, and effective.
      In order to improve the access of such patients to early intervention, 3
      interdependent solutions are proposed:The development of more interventional
      programs at those hospitals without cardiac surgical facilities that can meet
      rigorous standards. The development of protocols to insure the early and more
      frequent transfer of patients with high-risk ACS to interventional centers for
      coronary angiography and revascularization. The pre-hospital triage of patients
      with AMI to established heart attack centers with 24-hour, 365-day emergency
      interventional capability for immediate primary angioplasty (after the model of
      trauma centers). Universal triage/transfer of all such patients to interventional
      centers could, however, quickly flood the capability of all tertiary surgical
      hospitals. With the aging of the 'baby boomers' in the near future, the need for
      interventional facilities will increase even further. Thus the second and third
      solutions above will ultimately depend on the first solution. Improving the
      delivery of interventional therapy to patients with ACS can provide a substantial
      healthcare benefit to society.

PMID- 14728020
TI  - Effect of antihypertensive agents on arterial stiffness as evaluated by pulse
      wave velocity: clinical implications.
AB  - Structural and functional properties of the arterial wall have been reported to
      be altered in hypertension, even at early stages of the disease. Morbidity and
      mortality associated with hypertension are primarily related to arterial damage
      that may affect one or several organs. Considering the potential implications of
      arterial assessment in the prevention of cardiovascular disease, evaluation of
      the arterial effects of antihypertensive agents is recommended by numerous
      authorities. Among the noninvasive and simple methods to evaluate large arteries,
      pulse wave velocity (PWV) measurement is widely used as an index of regional
      arterial stiffness. This method is related to the arterial geometry and wall
      function, simple and reproducible, and thus, can easily be applied in clinical
      trials. Several studies performed in various populations showed significant
      powerful interactions between PWV and cardiovascular risk factors. In addition,
      aortic PWV was shown to be a forceful marker and predictor of cardiovascular risk
      in normotensive individuals and patients with hypertension. Furthermore, aortic
      PWV was shown to be an independent predictor of all-cause mortality in patients
      with essential hypertension. In comparison with placebo, clinical studies have
      shown that in short and long term trials, antihypertensive agents improved
      arterial stiffness (as evidenced by a reduction in PWV) independently of blood
      pressure reduction. The decrease of PWV was more pronounced with long term
      treatment than with short term treatment. Whether antihypertensive agents differ
      in their arterial effects independently of blood pressure changes remains
      unclear. Pharmacological studies, generally performed in small numbers of
      patients, indicate that the effects of long term treatment with ACE inhibitors,
      calcium channel antagonists and some beta-blockers on arterial stiffness are
      generally similar. The effectiveness of an antihypertensive agent in reducing
      arterial stiffness may also be influenced by the genetic background of the
      patient. Recently, the Complior Study has shown the feasibility to assess
      arterial stiffness in clinical trials involving large populations using an
      automatic device for measuring PWV. Long term treatment with an ACE inhibitor,
      perindopril, was associated with a decrease in blood pressure and aortic PWV in
      patients with essential hypertension. In high risk patients with end-stage renal
      failure, ACE inhibitors effectively decreased arterial stiffness and had a
      favorable effect on survival which was independent of changes in blood pressure.
      The correlation between reversion of arterial stiffness and decrease in
      cardiovascular morbidity and mortality needs to be confirmed in populations of
      patients with lower cardiovascular risk.

PMID- 14728022
TI  - Electrotherapeutic management of patients with heart failure.
AB  - Heart failure is associated with poor long term survival due to progressive
      refractory heart dysfunction and sudden cardiac death. Cardiac resynchronization
      through atrio-biventricular pacing has been introduced to treat patients affected
      by drug-refractory heart failure with desynchronized ventricular activation, as
      for complete left bundle branch block. The technique is aimed to overcome
      interventricular and intraventricular conduction delays leading to ventricular
      dysynchrony, paradoxical septal wall motion, presystolic mitral regurgitation and
      reduced diastolic filling times. Short term studies demonstrated that
      biventricular pacing (and perhaps left ventricular pacing alone) may improve both
      systolic and diastolic function. Initial studies in patients receiving long term
      pacing consistently showed significant QRS shortening associated with improvement
      in symptoms, left ventricular ejection fraction, exercise tolerance, quality of
      life and New York Heart Association functional class. As far as sudden cardiac
      death prevention in heart failure is concerned, implantable cardioverter
      defibrillator (ICD) implantation has been demonstrated to be the most effective
      therapy in patients with prior cardiac arrest due to ventricular fibrillation or
      poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction,
      unsustained ventricular tachycardia and inducibility at electrophysiological
      study also may identify high risk patients requiring ICD implantation. Further
      studies are needed to evaluate the effect of cardiac resynchronization on hard
      end-points, such as survival and long term clinical outcome, and to upgrade risk
      stratification criteria to be used in selection of candidates for ICD
      implantation.

PMID- 14728023
TI  - Myocardial regeneration: present and future trends.
AB  - Cardiomyocytes are terminally differentiated and are unable to proliferate in
      response to injury. Genetic modulation, cell transplantation and tissue
      engineering promise a revolutionary approach for myocardial regeneration and
      tissue repair after myocardial injury. Current data derived from animal models
      suggest that it may be possible to treat heart failure by inserting genetic
      materials or myogenic cells into injured myocardium. Success with animal models
      has raised the hope for new treatment after heart attacks and could prove an
      alternative to transplantation, particularly in elderly patients for whom there
      is often a lack of donor hearts. This exciting research, however, still faces
      significant difficulties before it can develop into a clinical therapeutic tool
      and many challenges need to be overcome before cell transplantation, gene therapy
      and tissue engineering can be considered efficient, therapeutic strategies for
      myocardial regeneration.

PMID- 14728024
TI  - Patient self-monitoring of oral anticoagulant therapy: potential benefits and
      implications for clinical practice.
AB  - Coumarin derivatives are widely used oral anticoagulants for patients with
      chronic atrial fibrillation, venous thromboembolism, valvular heart disease,
      myocardial infarction or a mechanical prosthetic heart valve. Because of the
      narrow therapeutic window associated with coumarins and the potential for drug
      interactions, frequent monitoring of anticoagulation is required to maintain the
      International Normalized Ratio (INR) between 2.0 to 3.5 for most clinical
      indications. Monitoring of oral anticoagulant therapy is placing a considerable
      burden on healthcare providers because many patients require life-long treatment
      with coumarins, and because of an increasing number of elderly patients with
      conditions that are treated with coumarins. A novel approach that might, in part,
      address this healthcare need is patient self-monitoring of anticoagulation with a
      portable coagulometer. Several cohort studies and randomized controlled trials
      have found that anticoagulation self-monitoring is as good as, or better than,
      conventional monitoring in a specialized anticoagulation clinic or by a general
      practitioner. The advantages of anticoagulation self-monitoring include reduced
      patient inconvenience relating to anticoagulation clinic visits and laboratory
      monitoring of warfarin therapy, and fewer INR levels outside the therapeutic INR
      range if INR measurements are preformed more frequently with anticoagulation self
      monitoring. Thus, anticoagulation self-monitoring has the potential to reduce the
      incidence of thromboembolic and bleeding episodes in patients who are receiving
      long term oral anticoagulant therapy. The potential drawbacks of anticoagulation
      self-monitoring include the costs of the portable coagulometer. Additionally,
      self-monitoring is limited to patients who have the cognitive and physical
      capabilities to perform the technique required for the portable coagulometer.

PMID- 14728025
TI  - Management of hypertension in pregnancy.
AB  - Hypertension is an important cause of both maternal and fetal morbidity and
      mortality in pregnant women. There are still no definitive guidelines as to when
      and how patients should be treated, but it is important that appropriate
      treatment is initiated early in patients at highest risk and they are closely
      monitored. Hypertension in pregnancy can be a difficult condition to diagnose and
      treat because of the numerous and differing classification systems that have been
      used in the past. One classification system, which accounts for the multisystem
      involvement which can occur in pre-eclampsia and eclampsia, divides hypertension
      in pregnancy into 3 main groups: pre-eclampsia, gestational hypertension and
      chronic hypertension. Little benefit to the fetus has been shown from treating
      gestational and chronic hypertension, but studies in this area have been small
      and would not have had the power to show a difference in outcome between treated
      and untreated groups. However, the reduction in morbidity and mortality in the
      treatment of pre-eclampsia is significant. Therefore, all pregnancies complicated
      by hypertension require monitoring to detect the possible onset of superimposed
      pre-eclampsia/eclampsia. Institutions should have a management strategy for those
      mothers with severe hypertension including a multidisciplinary approach, where
      the patient is to be monitored and which antihypertensive agents are to be used.
      It should not be forgotten that the definitive treatment for severe hypertension
      is delivery of the fetus despite risks to fetal morbidity and mortality. This
      will reduce blood pressure, but hypertension per se may still persist post partum
      requiring short term therapy.

PMID- 14728026
TI  - Effects of antihypertensive agents on the left ventricle: clinical implications.
AB  - Hypertensive heart disease (HHD) is characterized by left ventricular hypertrophy
      (LVH), alterations of cardiac function, and coronary flow abnormalities. LVH is
      an independent cardiovascular risk factor related to cardiovascular complications
      in patients with hypertension. Therefore, a decrease in left ventricular mass is
      a therapeutic goal in these patients. The effect of the different
      antihypertensive agents on LVH regression has been studied in nearly 500 clinical
      trials. Most studies conclude that there is regression of LVH after significant
      decrease in blood pressure with most commonly prescribed antihypertensive agents.
      However, the ability to regress LVH is different between antihypertensive drug
      classes. ACE inhibitors and calcium channel antagonists are more potent in
      reducing left ventricular mass than beta-blockers, with diuretics falling in the
      intermediate group. Recent data suggest that angiotensin AT(1) receptor
      antagonists reduce left ventricular mass to a similar extent as ACE inibitors or
      calcium channel antagonists. Although a large number of studies have established
      that reversal of LVH decreases the occurrence of adverse cardiovascular events in
      patients with hypertension, the hypothesis that LVH regression is beneficial has
      not yet been conclusively proven. On the other hand, the time has come to revisit
      the current management of HHD simply focused on controlling blood pressure and
      reducing left ventricular mass. In fact, it is necessary to develop new
      approaches aimed to repair myocardial structure and protect myocardial perfusion
      and function and, in doing so, to reduce in a more effective manner, adverse risk
      associated with HHD. The identification of genes involved in both the process of
      HHD and the response to therapy may be critical for the development of these new
      approaches. This article will review briefly the available data on the effects of
      antihypertensive agents on HHD. In addition, the emerging new concepts on the
      pharmacology of hypertensive myocardial remodeling and the pharmacogenetic basis
      of the treatment of HHD will be also considered.

PMID- 14728027
TI  - Thrombolytic therapy for acute ischemic stroke.
AB  - Available evidence of thrombolysis in acute ischemic stroke comes from a series
      of recent trials conducted in patients with acute stroke, and from a meta
      analysis published in the Cochrane Library. The objective of this paper is to
      review the literature on tolerability and efficacy of thrombolytic therapy in
      patients with acute ischemic stroke, to find out what the level of evidence is
      for each thrombolytic drug, and what should consequently be done in the routine
      practice. This review is based on a bibliographic search of published meta
      analyses of randomized trials, published randomized trials, and ongoing
      randomized trials, with the outcomes of disability, death, and symptomatic
      intracerebral hemorrhages (fatal or non-fatal). Our primary end-point is a
      combination of death and disability, in terms of "death or dependency", with
      dependency defined as a modified Rankin Score (mRS) of >/=3. The level of
      evidence for the efficacy of a thrombolytic treatment is considered sufficient if
      there is both a statistically significant effect in the meta-analysis of all
      randomized trials, without statistically significant heterogeneity, together with
      one adequately powered and designed conclusive trial. Streptokinase has a clearly
      harmful effect, without any demonstrated benefit and must not be used in patients
      with acute ischemic stroke. The level of evidence of an effect of intra-arterial
      pro-urokinase to reduce death or dependency is low, available data are sparse
      (only 220 patients), the estimation of its real efficacy and tolerability remains
      unclear, and its use in clinical practice is not presently justified. The
      efficacy of alteplase has been incompletely demonstrated because the results vary
      across trials and type of outcomes (death, death or dependency), and the cut-off
      of the disability scale. There is a significant heterogeneity in the effect on
      death or dependency. However, we can conclude that there is a beneficial effect,
      but its clinical application is limited because of the absence of adequate
      criteria to identify patients most likely to benefit from treatment. Overall the
      use of alteplase in patients with acute stroke was associated with some benefit,
      but it significantly increased total mortality in two trials. Given the observed
      confidence interval (CI), the results are compatible with, in the best
      situtation, 203 advoided death or dependency and 61 avoided death per 1000
      treated patients, and at worst 77 avoided death or dependency and 38 extra deaths
      per 1000 treated patients. Further trials aimed at validating more discriminant
      selection criteria are mandatory.

PMID- 14728028
TI  - Therapeutic potential for endothelin receptor antagonists in cardiovascular
      disorders.
AB  - The endothelins are synthesized in vascular endothelial and smooth muscle cells,
      as well as in neural, renal, pulmonal, and inflammatory cells. These peptides are
      converted by endothelin-converting enzymes (ECE-1 and -2) from 'big endothelins'
      originating from large preproendothelin peptides cleaved by endopeptidases.
      Endothelin (ET)-1 has major influence on the function and structure of the
      vasculature as it favors vasoconstriction and cell proliferation through
      activation of specific ET(A) and ET(B) receptors on vascular smooth muscle cells.
      In contrast, ET(B )receptors on endothelial cells cause vasodilation via release
      of nitric oxide (NO) and prostacyclin. Additionally, ET(B) receptors in the lung
      are a major pathway for the clearance of ET-1 from plasma. Indeed, ET-1
      contributes to the pathogenesis of important disorders as arterial hypertension,
      atherosclerosis, and heart failure. In patients with atherosclerotic vascular
      disease (as well as in many other disease states), ET-1 levels are elevated and
      correlate with the number of involved sites. In patients with acute myocardial
      infarction, they correlate with 1-year prognosis. ET receptor antagonists have
      been widely studied in experimental models of cardiovascular disease. In arterial
      hypertension, they prevent vascular and myocardial hypertrophy. Experimentally,
      ET receptor blockade also prevents endothelial dysfunction and structural
      vascular changes in atherosclerosis due to hypercholesterolemia. In experimental
      myocardial ischemia, treatment with an ET receptor antagonist reduced infarct
      size and prevented left ventricular remodeling after myocardial infarction. Most
      impressively, treatment with the selective ET(A) receptor antagonist BQ123
      significantly improved survival in an experimental model of heart failure. In
      many clinical conditions, such as congestive heart failure, both mixed ET(A/B )as
      well as selective ET(A) receptor antagonism ameliorates the clinical status of
      patients, i.e. symptoms and hemodynamics. A randomized clinical trial showed that
      a mixed ET(A/B) receptor antagonist effectively lowered arterial blood pressure
      in patients with arterial hypertension. In patients with primary pulmonary
      hypertension or pulmonary hypertension related to scleroderma, treatment with a
      mixed ET(A/B) receptor antagonist resulted in an improvement in exercise
      capacity. ET receptor blockers thus hold the potential to improve the outcome in
      patients with various cardiovascular disorders. Randomized clinical trials are
      under way to evaluate the effects of ET receptor antagonism on morbidity and
      mortality.

PMID- 14728030
TI  - Gene therapy for ischemic heart disease: therapeutic potential.
AB  - Gene therapy is evolving as an alternative mode to pharmacological intervention
      in the treatment of cardiovascular diseases. Experimental observations indicating
      that introduction of genes encoding for angiogenic peptide growth factors could
      result in improvement in perfusion to ischemic myocardium have led to the
      initiation of a number of preliminary clinical trials to evaluate this
      therapeutic modality. Sustained expression of the growth factor product from
      somatic cells transfected with the DNA for that protein has proven to be one of
      the major advantages of a gene therapy based approach over administration of the
      recombinant protein. A number of gene therapy vectors have been developed,
      prominent among these being adenoviral vectors and naked plasmid DNA. Whereas
      plasmid DNA results in less efficient transfection, its tolerability profile may
      be superior to adenoviral vectors. Plasmid DNA is particularly suitable when the
      gene product to be produced is capable of being secreted by the cell which is
      producing it. Vascular endothelial growth factor (VEGF) is not only essential to
      the process of angiogenesis, but, because it can be secreted from intact cells,
      appears to be ideal for gene transfer therapy aimed at improving perfusion to
      ischemic myocardium. The DNA can be delivered to the myocardium by intra-arterial
      or intramuscular injection. At present, direct injection into the muscle either
      via a small thoracotomy incision or by use of a recently developed percutaneous
      catheter technique appears to be superior to arterial administration. Several
      clinical trials based on intramyocardial injection of VEGF DNA in patients with
      otherwise inoperable coronary artery disease and intractable angina pectoris have
      recently been completed. These phase I trials have documented the tolerability of
      gene transfer using plasmid DNA and show promise of being able to improve
      myocardial perfusion and reduce anginal symptoms in the majority of patients
      treated thus far. While the trials involving gene transfer via a thoracotomy did
      not allow for randomization to a placebo group, the recent advent of a
      percutaneous delivery modality has allowed for randomization which should enhance
      our ability to determine whether angiogenic gene therapy will prove to be as
      effective as initial results suggest. In the future, results from such randomized
      placebo-controlled trials, improvement in vectors utilized for gene transfer and
      innovative new delivery techniques will undoubtedly enhance the potential of this
      novel approach to myocardial revascularization.

PMID- 14728031
TI  - Alcohol and cardiovascular health: recent findings.
AB  - This review is focused on recent studies published since 1997 that have
      contributed toward our current thinking about the association between alcohol
      consumption and cardiovascular disease. Recent studies reinforce the consistent
      finding of a J-shaped inverse association between alcohol and cardiovascular
      disease morbidity and mortality, primarily due to an underlying association
      between alcohol and coronary heart disease (CHD). Despite the methodological
      difficulties of studying alcohol consumption, epidemiological studies are
      surprisingly consistent in showing that light to moderate alcohol intake has an
      inverse association with the risk of cardiovascular disease morbidity and
      mortality compared with those who do not drink at all. The depth and width of the
      J-shaped inverse association is largely dependent upon the underlying lowered
      risk of CHD. Alcohol likely reduces the risk of cardiovascular disease through
      increases in plasma high density lipoprotein-cholesterol (HDL-C) levels. Further
      support for the HDL-C hypothesis comes from the lack of a differential effect of
      alcohol by beverage type, suggesting that ethanol is responsible for the
      protective effect. While other mechanisms for a reduced risk of cardiovascular
      disease by alcohol have been suggested - including hemostatic markers and
      improvements and insulin sensitivity - evidence remains preliminary. The current
      recommendation set forth by the American Heart Association and other groups to
      limit alcohol intake to no more than 2 drinks per day for men and 1 drink per day
      for women appear justified but must be cautiously promoted. Although the
      association of alcohol and cardiovascular disease is likely to be causal, these
      recommendations must consider the complexity of the metabolic, physiological, and
      psychological effects of alcohol. In general, maximal benefits and safety appear
      to be at the level of approximately 1 drink per day. Limited data suggest that
      the level for optimal benefit and safety may be slightly lower for women. From a
      public policy standpoint, whether the benefits for cardiovascular disease persist
      at heavier drinking levels or are attenuated, may not be relevant since clear
      harm in terms of overall mortality would likely outweigh any benefits in the
      reduction of cardiovascular disease.

PMID- 14728032
TI  - What is the optimal blood pressure in patients with diabetes mellitus?
AB  - Cardiovascular disease is the number one cause of death in patients with type 2
      diabetes mellitus. This condition leads to an increased risk of premature
      mortality in patients with ischemic heart disease and stroke. Many risk factors
      besides hyperglycemia in itself contribute to this increased risk, acting in a
      synergistic fashion. One of the most important risk factors is hypertension.
      Several recent clinical trials have shown the benefits of reducing high blood
      pressure in patients with diabetes mellitus to lower levels than have previously
      been recommended in clinical guidelines. In both the United Kingdom Prospective
      Diabetes Study (UKPDS) and the Hypertension Optimal Treatment (HOT) study a
      significant trend for increased benefits associated with lower diastolic blood
      pressure levels was shown. Therefore, clinicians should be encouraged to do more
      to treat hypertension in patients with type 2 diabetes mellitus and increase the
      proportion of patients in whom acceptable blood pressure control is achieved. For
      example, in Sweden, acceptable blood pressure control is currently only achieved
      in about 20 to 25% of patients with type 2 diabetes mellitus. Recent evidence
      also points to the primary importance of a tight blood pressure control. This
      implies drug combination treatment for the majority of patients. Therefore, the
      clinician must be able to use a broad variety of antihypertensive drugs, and from
      these drugs choose alternative combinations with pharmacological synergism.

PMID- 14728033
TI  - Etiology and management of sustained ventricular tachycardia.
AB  - Ventricular tachyarrhythmias secondary to a variety of underlying cardiovascular
      problems pose a therapeutic challenge to the clinician. The initial presentation
      may be as sudden cardiac death, which underlies its public health problem. The
      underlying conditions predisposing to this arrhythmia include ischemic heart
      disease, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmiogenic
      right ventricle dysplasia and certain postoperative states including corrective
      surgery for tetralogy of Fallot and valve replacement. Other causes include
      prolonged QT syndrome, idiopathic right and left ventricle tachycardia and bundle
      branch re-entry tachycardia. Ischaemic heart disease is the most common cause of
      ventricular tachycardia and therapy has evolved considerably over the past two
      decades. The development of and refinements in the implantable cardioverter
      defibrillator (ICD) have introduced a new dimension in therapeutic options and
      markedly improved survival in these patients. Insights in the dichotomy between
      arrhythmia suppression and total mortality have reoriented drug therapy with a
      decrease in the use of sodium channel blockers. beta-blockers have emerged as
      antiarrhythmic drugs in their own right and their synergistic effects with
      amiodarone have strengthened the antiarrhythmic drug arm. The role of these drugs
      in patients with hemodynamically stable ventricular tachycardia, especially in
      relatively preserved ventricles needs to be explored. Catheter ablation
      techniques have provided curative therapy in patients with idiopathic and bundle
      branch reentry tachycardia. Further advances in radiofrequency ablation,
      including use of newer mapping techniques, promise a greater role for ablation of
      ischemic ventricular tachycardia in the future. A hybrid approach consisting of
      drugs, catheter ablation and/ or ICD may provide effective therapeutic approach
      in some situations. Further innovations and technologic developments promise a
      further reorientation in therapy towards identification and treatment of the
      underlying arrhythmogenic substrate.

PMID- 14728034
TI  - Systematic review of the efficacy and safety of perhexiline in the treatment of
      ischemic heart disease.
AB  - Perhexiline was introduced about 30 years ago and rapidly gained a reputation for
      efficacy in the management of angina pectoris. However, hepatic and neurological
      adverse effects associated with perhexiline administration led to a marked
      decline in its use. The drug was originally classified as a coronary vasodilator,
      and later as a calcium channel antagonist, but recent data suggests that it acts
      as a cardiac metabolic agent, through inhibition of the enzyme, carnitine
      palmitoyltransferase-1 (CPT-1). Given the drug's unique anti-ischemic action and
      favorable hemodynamic profile, together with an improved understanding of the
      mechanisms underlying the adverse effects of the drug and the clear clinical need
      for additional therapies in refractory patients, perhexiline is currently being
      re-appraised as a potentially useful agent in the management of severe myocardial
      ischemia. Perhexiline is being considered for registration or re-registration in
      a number of countries and is being evaluated in a large-scale clinical trial in
      elderly patients with aortic stenosis and myocardial ischemia. This systematic
      review examines the evidence from available published literature in relation to
      the efficacy and tolerability of perhexiline in the treatment of cardiac disease.
      While there is a lack of well designed controlled trials using objective end
      points to determine efficacy (almost all trials used a crossover design, included
      small numbers of patients and had limited statistical analysis of results), there
      is consistency in the data available that perhexiline is considerably more
      effective than placebo when used as monotherapy. Furthermore, it affords
      additional symptom relief in those already receiving maximal conventional anti
      anginal therapy. However, there is a paucity of trials demonstrating the efficacy
      of low dosages of perhexiline (100 to 200 mg/day) in patients with refractory
      angina pectoris. Available evidence also suggests that the incidence of adverse
      events can be minimised, and the efficacy maintained, by keeping plasma
      perhexiline concentrations within a therapeutic range (150 to 600 micro g/L)

PMID- 14728035
TI  - Inpatient costs of major cardiovascular events.
AB  - OBJECTIVE: Many trials of new therapies for cardiovascular disease include
      economic measures to assess the impact of treatment on healthcare costs, however,
      it is difficult to compare results between trials due to variation in methods for
      assigning costs. Therefore we developed a standard library of inpatient hospital
      costs for major cardiovascular events commonly reported in trials for new
      cardiovascular therapies. DESIGN: Mean and median hospital charges for each event
      were calculated from Medicare admissions selected by ICD-9-CM codes from the most
      recent Healthcare Cost and Utilisation Project (HCUP) Nationwide Inpatient Sample
      (NIS) database available. Charges were converted to costs using the cost-to
      charge ratio from the most recent Medicare cost report data and updated to 1999
      using a model derived from the Medicare Payment Advisory Commission (MedPAC)
      forecast to recommend annual updates to Medicare. RESULTS: Total hospital costs
      for medical events ranged from $US3654 (1999 values) to $US7833; total hospital
      costs for surgery and procedures ranged from $US7054 to $US46 317. The
      distribution of hospital costs is skewed with median costs and lengths of stay
      lower than mean values. Costs for patients who died in the hospital were
      generally higher than costs for patients who were discharged. CONCLUSIONS: The
      library of costs was calculated using a uniform method based on publicly
      available and easily accessible data and may be updated from year to year. This
      method provides standardised estimates of hospital costs that can be used in
      economic analyses of cardiovascular clinical trials.

PMID- 14728037
TI  - New strategies to prevent restenosis.
AB  - The Holy Grail of cardiovascular pharmacology has been the search for an
      effective therapy targeting restenosis after angioplasty and/or intra-arterial
      stenting. The failure of promising therapeutics in clinical trials underscores
      the complexity and redundancy of the signaling cascades regulating mitogenesis
      and fibrogenesis. Novel therapeutic modalities have potential to target
      dysfunctional signaling elements directly in vascular smooth muscle cells.
      Significant progress in the treatment against restenosis will require the
      exploitation and cross-fertilization of developments in the fields of
      pharmacology, bioengineering, genetics, and molecular biology. Collaboration
      among researchers in these fields will be essential.

PMID- 14728038
TI  - Patients with atherosclerotic vascular disease: how low should plasma
      homocyst(e)ine levels go?
AB  - Plasma homocyst(e)ine level is a strong independent risk factor for vascular
      disease. The spelling of homocyst(e)ine reflects that what is measured, and what
      constitutes the risk factor; it includes homocysteine, homocystine (the dimer of
      homocysteine) and mixed cysteine-homocysteine disulfide. Homocyst(e)ine levels
      above 10.2 micro mol/L are associated with a doubling of coronary risk, and
      levels above 20 micro mol/L are associated with a 9.9-fold increase in risk
      compared with levels below 9 micro mol/L. The mechanisms by which homocyst(e)ine
      promotes vascular disease include increased thrombosis, consumption of nitric
      oxide, endothelial injury, and reduced thrombolysis. Homocyst(e)ine is an
      independent predictor of carotid atherosclerosis. Vitamin therapy with folate,
      pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) reduces blood
      levels of homocyst(e)ine, improves endothelial function, reduces levels of
      fibrinogen and lipoprotein(a), improves thrombolysis, and in uncontrolled
      clinical observation, leads to regression of carotid plaque. These lines of
      evidence support a causal relationship between homocyst(e)ine and
      atherosclerosis, and suggest that in patients with vascular disease, an
      appropriate target level for therapy may be below 9 or 10 micro mol/L. Randomized
      controlled studies are under way to determine whether vitamin therapy is
      effective in secondary prevention of myocardial infarction and stroke.

PMID- 14728039
TI  - Pharmacologic management of arrhythmias in patients with congenital heart
      disease.
AB  - The management of cardiac arrhythmias has evolved rapidly over the past decade.
      This includes the development of more effective antiarrhythmic medications as
      well as catheter- and device-based therapies. Antiarrhythmic medications remain
      the primary treatment modality for most acute arrhythmias; however, the long term
      use of these medications may be accompanied by severe adverse effects. For this
      reason, antiarrhythmic medications are increasingly used in conjunction with
      other forms of therapy, such as catheter ablation or pacemaker implantation.
      Patients with congenital heart disease often have an increased propensity for
      cardiac arrhythmias due to both inherent conduction system abnormalities and
      impaired ventricular function. The purpose of this review is to examine the
      currently available antiarrhythmic drugs and assess their role in the treatment
      of arrhythmias in patients with congenital heart disease. It is important to
      emphasize that patients with congenital heart disease often have hemodynamic
      limitations and may be at an increased risk for developing adverse effects with
      antiarrhythmic agents. An awareness of the arrhythmias associated with congenital
      heart disease, the natural history of these arrhythmias, and the potential
      benefit of treatment with antiarrhythmic medications versus other forms of
      therapy provides a rational basis for therapy in this challenging population of
      patients.

PMID- 14728040
TI  - Mechanisms underlying ventricular arrhythmias in idiopathic dilated
      cardiomyopathy: implications for management.
AB  - Ventricular arrhythmias (VA) have been associated with mortality in idiopathic
      dilated cardiomyopathy (IDCM). All 3 main mechanisms of arrhythmogenesis -
      reentry, trigger activity, and automatism - have been implicated. Arrhythmogenic
      substrates in IDCM favor these mechanisms and are often potentiated by
      electrolyte imbalance secondary to diuretic treatment, by antiarrhythmic drugs,
      or by bradycardia, leading to polymorphic ventricular tachycardia (VT).
      Myocardial macroreentry is the mechanism most frequently responsible for
      monomorphic VT in IDCM; however, focal activation and His-Purkinje macroreentry
      are often responsible and, especially in the latter case, are frequently
      unrecognized. Clinical suspicion and final recognition by electrophysiologic
      testing have important therapeutic consequences, because both focal activation
      and His-Purkinje macroreentry can be treated effectively by catheter ablation. On
      the other hand, the frequent recurrences of myocardial macroreentrant VT after
      ablation require this therapy to be used in combination with drugs or an
      implantable cardioverter defibrillator (ICD). beta-Adrenoceptor antagonists (beta
      blockers) have a beneficial effect for primary prevention of VA in IDCM. Type III
      antiarrhythmics have a neutral effect on mortality and type I antiarrhythmics
      should be avoided. Treatment of nonsustained VT in IDCM is controversial because
      it often presents without symptoms and is linked more to overall mortality than
      to arrhythmic mortality. Empiric treatment with amiodarone or
      electrophysiologically guided sotalol are preferred to the use of other drugs for
      secondary prevention of sustained VA. ICDs should be implanted in patients who
      have been resuscitated from cardiac arrest due to VA, or in those with poorly
      tolerated VT and severe left ventricular dysfunction. Empiric treatment with
      amiodarone or electrophysiologically guided class III antiarrhythmics may also be
      alternatives for patients with IDCM and no severe left ventricular dysfunction,
      especially if VT is well tolerated.

PMID- 14728041
TI  - Drug treatment of patients with decompensated heart failure.
AB  - Decompensated heart failure (HF) may be defined as sustained deterioration of at
      least one New York Heart Association functional class, usually with evidence of
      sodium retention. Episodes of decompensation are most commonly precipitated by
      sodium retention, often associated with medication noncompliance. Our therapeutic
      approach to hospitalized patients is based on the documented hemodynamic
      responses to vasodilator therapy, with redistribution of mitral regurgitant flow
      to forward cardiac output and decompression of the left atrium. Invasive
      hemodynamic monitoring is seldom required for the effective management of
      patients with HF and there are risks associated with pulmonary artery
      catheterization. The currently available parenteral vasoactive drugs for
      decompensated heart failure include: (i) vasodilators such as nesiritide,
      nitroprusside and nitroglycerin (glyceryl trinitrate); (ii) catecholamine
      inotropes, primarily dobutamine; and (iii) inodilators such as milrinone, a
      phosphodiesterase inhibitor. Vasodilators are most appropriate for those patients
      who are primarily volume-overloaded, but with adequate peripheral perfusion. In
      this class of agents, nesiritide (recombinant human B-type natriuretic peptide)
      offers advantages over currently available drugs. Nesiritide produces rapid and
      sustained decreases in right atrial and pulmonary capillary wedge pressures, with
      reduction in pulmonary and systemic vascular resistance and increases in cardiac
      index. The hemodynamic effects of nesiritide infusion were sustained over a
      duration of 1 week and the drug may be used without intensive monitoring in
      patients with decompensated HF. Treatment with dobutamine is indicated in
      patients in whom low cardiac output rather than elevated pulmonary pressure is
      the primary hemodynamic aberration. However, milrinone reduces left atrial
      congestion more effectively than dobutamine, and is well tolerated and effective
      when used in patients receiving beta-blockers. In-patient therapy for
      decompensated HF is a short term exercise for symptom relief and provides an
      opportunity to re-assess management in the continuum of care.

PMID- 14728042
TI  - Current management of symptomatic atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most commonly encountered sustained arrhythmia.
      Heart rate control, reduction of symptoms, and prevention of embolism are major
      goals of treatment. Whether the strategy of cardioversion with subsequent
      maintenance of sinus rhythm has an advantage over heart rate control is under
      active investigation. Digoxin, non-dihydropyridine calcium channel antagonists,
      beta-adrenoceptor antagonists (beta-blockers), and amiodarone are the
      pharmacologic agents most commonly used to achieve rate control. In patients with
      drug-resistant AF, atrioventricular nodal ablation (or modification) with
      implantation of a permanent pacemaker is an alternative therapy. Conversion to
      sinus rhythm can best be achieved by electrical cardioversion. In selected
      patients, pharmacologic cardioversion can also be attempted. The use of
      antiarrhythmic drugs for the maintenance of sinus rhythm depends on several
      factors: (i) the nature of the arrhythmia (first attack, paroxysmal AF with
      frequent attacks, paroxysmal AF with infrequent attacks, or persistent AF); (ii)
      the associated symptoms; (iii) and the risk of severe adverse effects associated
      with the chosen drug. If the administration of an antiarrhythmic drug is
      appropriate, the choice of the drug must be tailored to the specific
      characteristics of the given patient. In lone AF, class Ic antiarrhythmic drugs
      are the best tolerated. These agents should be combined with a calcium channel
      antagonist or a beta-blocker to prevent rapid ventricular response in the case of
      conversion of AF to atrial flutter. In this situation, catheter ablation of
      atrial flutter at the isthmus (hybrid therapy) should be performed. All class I
      antiarrhythmic agents should be avoided in patients with structural heart
      disease. Alternative approaches that may be used if sinus rhythm cannot be
      maintained with drug therapy include: (i) the ablation of arrhythmogenic
      pulmonary veins; (ii) the implantation of an atrial defibrillator; (iii) the use
      of specific pacing sites; (iv) or pacing modes. Whether these approaches will
      reach clinical relevance merits further investigation. Intraoperative catheter
      ablation or surgical ablation (maze procedure) seems a promising approach for
      curing AF in patients undergoing cardiac surgery. Among all of the available
      treatment options, the most consistent proof of efficacy in reducing mortality
      and morbidity from AF exists for antithrombotic treatment.

PMID- 14728043
TI  - Colesevelam.
AB  - Colesevelam, a bile acid sequestrant used in the treatment of patients with
      hypercholesterolemia, is a lipid-lowering polymer that has high affinity for bile
      acids. In animals colesevelam was not systemically absorbed after oral
      administration and was rapidly eliminated via the gastrointestinal tract.
      Colesevelam did not alter the serum concentrations or pharmacokinetic properties
      of drugs from several different classes in healthy volunteers. Colesevelam
      administered orally in patients with primary hypercholesterolemia significantly
      reduced serum levels of low density lipoprotein (LDL)-cholesterol and total
      cholesterol. This lipid-lowering activity was sustained during short (6 weeks)
      and longer term (24 weeks) treatment. Combination therapy with colesevelam plus
      hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (lovastatin,
      simvastatin or atorvastatin) was associated with additive reductions in serum
      levels of LDL-cholesterol and total cholesterol, relative to either agent alone.
      Colesevelam treatment was well tolerated and lacked severe gastrointestinal
      adverse events typical of other bile acid sequestrants (bloating, flatulence,
      heartburn and nausea). The most frequently reported adverse events were
      constipation and dyspepsia. In humans colesevelam did not induce clinically
      significant changes in serum levels of vitamins, coagulation parameters or liver
      enzymes.

PMID- 14728047
TI  - Beta-blockade in heart failure: selective versus nonselective agents.
AB  - Controlled clinical trials performed in more than 13 000 patients have, to date,
      consistently shown the beneficial effects of long term beta-adrenoceptor
      antagonist (beta-blocker) therapy in patients with chronic heart failure. It is
      not clear whether this represents a class effect or whether it is specific only
      to some agents. Beneficial effects on the prognosis of patients with mild to
      moderate heart failure have been shown with metoprolol, bisoprolol, and
      carvedilol. These beta-blockers, however, differ in their pharmacologic
      characteristics. Metoprolol and bisoprolol are selective for beta(1)-adrenergic
      receptors and are devoid of ancillary properties. Carvedilol, at a dosage of 50
      mg/day, blocks all beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors, and it
      has associated antiproliferative and antioxidant activities. These differences
      cause a varied acute hemodynamic response, with a reduction in cardiac output and
      a tendency toward a rise in pulmonary wedge pressure with selective agents and no
      change in cardiac output and a slight decrease in pulmonary pressures with
      carvedilol. Accordingly, when the therapy is started, the most frequent adverse
      effects are worsening heart failure with metoprolol and bisoprolol, and
      hypotension and dizziness with carvedilol. It remains controversial whether these
      differences also influence the long term effects of therapy. Carvedilol may
      provide a more comprehensive blockade of the cardiac adrenergic drive than
      selective beta-blockers because it does not upregulate beta(1)-adrenergic
      receptors, blocks all adrenergic receptors and decreases cardiac norepinephrine
      release. These properties may lead to a larger increase in left ventricular
      function and a lack of improvement in maximal exercise capacity with carvedilol,
      compared with selective beta-blockers. It is, however, unclear whether these
      differences also influence patient outcome. The long term effects of different
      beta-blockers on prognosis are currently being compared in the Carvedilol or
      Metoprolol European Trial (COMET) in which more than 3000 patients with chronic
      heart failure have been randomized in a 1 : 1 ratio to receive metoprolol or
      carvedilol.

PMID- 14728048
TI  - Clinical potential of photodynamic therapy in cardiovascular disorders.
AB  - Atherosclerosis and intimal hyperplasia remain obstacles for surgeons to overcome
      following vascular reconstructions. Even with all of the technical improvements
      that have occurred in the past several decades, long term patency following
      intervention is hindered by these inherent adverse developments. Today, the use
      of light is seen as a potential treatment modality in vascular surgery.
      Photodynamic therapy (PDT) has been used in the treatment of cancer, and because
      of its continued success in vascular experimental models it is now being tested
      in clinical trials for vascular diseases. PDT offers the surgeon many advantages,
      and it may have unlimited uses in the clinical setting. Is PDT the ultimate
      treatment modality for the cardiovascular surgeon and will it help to overcome
      the inherent failures associated with vascular reconstructions? It may be too
      early to answer these questions, but with the current successes demonstrated by
      PDT, there is a need for further testing in clinical trials. In the near future,
      PDT may be used clinically as a treatment modality to inhibit restenosis and
      intimal hyperplasia following surgical intervention.

PMID- 14728049
TI  - Role of metabolically active drugs in the management of ischemic heart disease.
AB  - This article reviews the fundamentals of myocardial energy metabolism and
      selectively outlines the use of several metabolically active drug therapies in
      the treatment of ischemic heart disease. These drugs - ranolazine, trimetazidine,
      dichloroacetate (DCA), glucose-insulin-potassium (GIK) solutions, and L-carnitine
      - have mechanisms of action distinct from traditional anti-ischemic drugs. These
      agents work by shifting myocardial energy metabolism away from fatty acids toward
      glucose as a source of fuel. Because these agents are well tolerated and do not
      affect heart rate or blood pressure, they conceivably could supplement
      traditional anti-ischemic drug therapy with little risk. The background,
      rationale for use, and published literature on each agent is reviewed, and the
      outcomes of pertinent clinical trials are discussed. In the case of ranolazine,
      data suggest benefit in the treatment of stable angina pectoris, particularly
      with sustained release formulations. Trimetazidine appears to have similar
      physiologic effects to ranolazine, and it is effective as monotherapy and as
      additive therapy in patients with chronic ischemic heart disease. DCA improves
      acidosis in critically ill patients and, likewise, improves myocardial
      hemodynamics in those with chronic coronary artery disease and congestive heart
      failure; however, its metabolism is variable and clinical data on its use in
      chronic ischemic heart disease are limited. GIK solutions have been shown to be
      beneficial in animal and human models of ischemia and acute myocardial
      infarction, and they offer an inexpensive means by which to improve the oxidation
      of glucose in the heart. Lastly, a large body of literature suggests a benefit
      with L-carnitine in a number of cardiovascular illnesses, including ischemic
      heart disease. Clinical trial data in acute myocardial infarction are promising
      and have prompted the initiation of a large-scale mortality trial.

PMID- 14728050
TI  - Medical management of chronic heart failure in children.
AB  - Chronic heart failure (CHF) in children occurs mostly as a result of systolic
      dysfunction of the systemic ventricle or of congenital defects leading to large
      left-to-right shunts and pulmonary overcirculation. The ensuing symptoms and
      signs are similar in both cases, and include respiratory distress, poor feeding
      and growth, and hepatic congestion. Grading the severity of the symptoms
      accurately and reproducibly is important for studying CHF and the response to
      therapy. The Ross classification for young children and the New York Heart
      Association classification for older children are frequently utilized for such
      grading. The standard therapy for CHF in children consists of diuretics, to
      reduce cardiac preload and improve symptoms, and the maximization of nutritional
      support. The role of digoxin in treating CHF in children is controversial,
      especially regarding those children with pulmonary overcirculation where the
      function of the systemic ventricle is usually well preserved. As the importance
      of neurohormonal changes in the pathogenesis of worsening CHF is elucidated,
      newer medications aimed at counteracting such changes are becoming more important
      in the medical therapy of CHF in children. ACE inhibitors improve function and
      survival in adults with CHF, and they probably do the same in children with
      systemic ventricular dysfunction. It is less clear how effective they are in
      pulmonary overcirculation, but patients with high flow and low pulmonary
      resistance are most likely to benefit. In infants receiving treatment with ACE
      inhibitors, it is necessary to monitor for renal insufficiency or renal failure.
      beta-Adrenoceptor blockade has also been established as an effective therapy for
      adults with CHF with beneficial effects on survival and left ventricular
      function. While data for the pediatric population are limited, early studies
      suggest that beta-adrenoceptor antagonists (beta-blockers) may work well in
      infants and children with CHF. Caution must be used by starting treatment with
      very low dosages of beta-blockers and gradually increasing to the desired goals
      with close monitoring of blood pressure and heart rate. It is clear that larger
      multicenter trials are crucial to our ability to provide the most appropriate
      treatment for children with CHF. The demand for effective medical treatment will
      increase as more patients with palliated single ventricles survive surgery and
      then develop CHF from dysfunction of a hypertrophic and dilated single ventricle.

PMID- 14728051
TI  - Current management of acute symptomatic deep vein thrombosis.
AB  - Venous thromboembolism is a common and potentially fatal disease. If properly
      used, anticoagulation therapy is effective in preventing recurrence of venous
      thromboembolism and in improving survival. Symptomatic patients with an objective
      diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should
      receive immediate systemic heparin anticoagulation at dosages sufficient to
      rapidly prolong the activated partial thromboplastin time into the laboratory
      specific therapeutic range; this range corresponds to a plasma heparin
      concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration),
      or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should
      be started within 24 hours after starting heparin; the starting dose should be
      the estimated patient-specific daily dose with no loading dose. Heparin and
      warfarin anticoagulation should be overlapped for at least 4 to 5 days and until
      the international normalized ratio (INR) is within the therapeutic range (2.0 to
      3.0) on 2 measurements made at least 24 hours apart. The duration of warfarin
      anticoagulation should be individualized based on the respective risks of venous
      thromboembolism recurrence and anticoagulant-related bleeding. In general,
      warfarin should be continued for at least 3 months, and longer for patients with
      recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic
      disease with extremity paresis, obesity, or laboratory evidence of a lupus
      anticoagulant/anticardiolipin antibody, homozygous carrier or combined
      heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A
      mutations, and possibly deficiency of either antithrombin, protein C, or protein
      S. Low molecular weight heparin (LMWH) is effective and well tolerated as acute
      therapy for patients with DVT or stable PE, and does not require laboratory
      monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and
      cost effective for most patients with DVT, and possibly for selected patients
      with PE.

PMID- 14728052
TI  - Tenecteplase: a review of its pharmacology and therapeutic efficacy in patients
      with acute myocardial infarction.
AB  - Tenecteplase is a triple combination mutant variant of alteplase with high fibrin
      specificity and resistance to plasminogen activator inhibitor-1. The reduced rate
      of systemic clearance of the drug relative to alteplase allows tenecteplase to be
      given by rapid bolus injection to patients with acute myocardial infarction (AMI)
      with ST segment elevation. The efficacy of tenecteplase in AMI has been
      demonstrated in a phase I dose-ranging trial [Thrombolysis in Myocardial
      Infarction (TIMI) 10A], a nonblind phase II comparison with alteplase (TIMI 10B),
      and a randomized double-blind phase III comparison with alteplase in 16 949
      patients [the second Assessment of the Safety and Efficacy of a New Thrombolytic
      (ASSENT-2) trial]. Patients also received aspirin and intravenous heparin in all
      trials. In TIMI 10A and 10B, TIMI grade 3 coronary flow was achieved after 90
      minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50 mg; in
      TIMI 10B, grade 3 flow was reported in 62.7% patients receiving alteplase
      (</=100mg by front-loaded infusion over 90 minutes). Thirty-day mortality was
      similar with bodyweight-adjusted intravenous bolus doses of tenecteplase 30 to
      50mg and front-loaded 90-minute infusion of alteplase in ASSENT-2 (approximately
      6.2%). Rates of reinfarction and cardiogenic shock were also similar between
      groups, although mortality was reduced with tenecteplase in patients receiving
      treatment more than 4 hours after onset of symptoms (7 vs 9.2%; p = 0.018).
      Preliminary data show maintenance of the similarity between groups over 1 year
      (approximate 10.2% mortality in both groups), with loss of statistical
      significance between groups in patients treated late. ASSENT-2 showed the risks
      of intracranial hemorrhage (0.93%) and stroke (all causes) [1.78%] with
      tenecteplase to be similar to those with alteplase (0.94 and 1.66%,
      respectively). The rate of noncerebral bleeding was lower with tenecteplase than
      with alteplase (26.43 vs 28.95%; p = 0.0003). No causal link has been
      demonstrated between tenecteplase and allergic reactions in patients.
      CONCLUSIONS: Bolus tenecteplase is an effective thrombolytic agent, suitable for
      first-line use in patients with AMI with ST segment elevation. Results to date
      show overall efficacy and tolerability profiles similar to those of alteplase,
      with comparable mortality after 1 year's follow-up. The apparent advantages of
      tenecteplase (reduced mortality in patients receiving late treatment and reduced
      incidence of noncerebral bleeding complications) in ASSENT-2 are of interest and
      merit further attention. The full implications of the availability of bolus
      administration and its potential clinical advantages over the currently widely
      used infusion regimens, together with the effect on outcomes of addition of
      tenecteplase to platelet glycoprotein IIb/IIIa inhibition, are currently under
      investigation.

PMID- 14728054
TI  - Direct-to-consumer marketing of prescription drugs: a current perspective for
      neurologists and psychiatrists.
AB  - In the US and New Zealand, the past decade has seen tremendous growth in the
      marketing of prescription drugs directly to patients. The pharmaceutical industry
      has applied pressure in other countries to relax regulations governing such
      marketing although this has not yet been successful. While we still have much to
      learn about the potential impact on the public's health of direct-to-consumer
      (DTC) marketing, some data are available. This article summarises the current
      literature on the benefits and risks of DTC marketing. This marketing strategy
      has grown substantially in the US, but only select drugs are advertised. Whether
      there is net benefit or harm to the public's health as a result of DTC marketing
      depends critically on which drugs are advertised and the quality of the
      information provided in promotional material. Critical reviews of this
      promotional material suggest the information is of poor quality. Notably, 18% of
      the 50 drugs advertised most intensively in the US were medications used to treat
      psychiatric and neurological disorders. The impairments in decisional capacity
      often seen in psychiatric and neurological illness leave patients vunerable to
      the controlling influence of DTC marketing and, thus, undermine the patient
      autonomy that is said to be promoted by this marketing strategy. If there is any
      benefit from DTC marketing it is for significantly undertreated conditions.
      International restrictions on DTC marketing should remain in place until further
      evidence of net benefit or harm emerges from the DTC marketing experiment that is
      taking place in the US and New Zealand.

PMID- 14728055
TI  - Cholinesterase inhibitors and vascular dementia: another string to their bow?
AB  - Two of the four licensed cholinesterase inhibitors, galantamine and donepezil,
      have recently featured in published work showing how they act in dementia
      associated with cerebrovascular disease (CVD). It is timely to review this new
      evidence and place it within the current consensus understanding of what makes up
      a clearly heterogeneous dementia population. To do this, the current review
      explores the relationship between Alzheimer's disease, for which this group of
      compounds originally received licensing approval, and vascular pathology within
      the brain, highlighting the significant overlap in risk factors and the frequent
      coexistence of the two conditions in the patients that are studied. Whether they
      are inter-related or separate entities is discussed, followed by a description of
      the current classifications of Alzheimer's disease with CVD, and the three
      subtypes of 'pure' vascular dementia - subcortical, cortical and strategic
      infarct. Understanding these entities allows more accurate diagnostic and
      prognostic information to be given to patients, and leads towards matching the
      published clinical evidence discussed with more predictable clinical syndromes.
      This distinction is particularly relevant in terms of the studies conducted thus
      far. Galantamine has been studied in a placebo-controlled study of patients with
      Alzheimer's disease and CVD as well as patients with vascular dementia, whereas
      donepezil was studied exclusively in patients with vascular dementia. Differences
      in the way the placebo groups acted in these studies confirmed the fact that
      these actually are two distinct groups. Galantamine showed efficacy across the
      combined groups studied, with placebo deterioration similar to previous
      Alzheimer's disease studies, while donepezil produced a positive effect in
      vascular dementia - with this placebo group relatively unchanged. The symptomatic
      improvements seen were not really surprising, as cholinergic deficits are a
      common factor across all of these syndromes. Wherever this is the predominant
      biological finding, it would be expected that cholinesterase inhibitors would
      have a similar effect, whatever the condition causing it.

PMID- 14728057
TI  - Treatment benefit and daily drug costs associated with treating Parkinson's
      disease in a Parkinson's disease clinic.
AB  - OBJECTIVE: In some countries, such as Germany, there has been a move towards the
      treatment of patients with Parkinson's disease in specialised inpatient units.
      However, data on patient outcome and the daily costs of antiparkinsonian drugs in
      these settings are rare. This study was conducted to determine the effect of an
      inpatient setting (a specialised Parkinson's disease clinic) on drug therapy
      costs and patient symptoms. PATIENTS AND METHODS: This study involved 63
      consecutively referred inpatients of a Parkinson's disease clinic. On entry to
      the clinic, the patients' antiparkinsonian drug regimen was titrated in order to
      improve their motor function. The daily costs of drug therapy per patient (in
      2002 values) were calculated, and the severity of Parkinson's disease symptoms
      scored via scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and
      standardised instrumental procedures (peg insertion and tapping), both initially
      and at the end of the patients' stay in the clinic. The variables between the two
      evaluation timepoints were compared. RESULTS: The titration of antiparkinsonian
      drugs was associated with a significant decrease in the symptoms of Parkinson's
      disease at discharge from the clinic compared with admission (as measured by
      UPDRS total and subscale scores [all p < 0.001], and, to a lesser extent, by peg
      insertion and tapping [both p < 0.05]). A significant increase in daily drug
      costs (an increase of euro14.11 per patient for all drugs and euro12.36 per
      patient for antiparkinsonian drugs [both p <0.001]) was also observed.
      CONCLUSION: The results demonstrate that the symptoms experienced by patients
      with Parkinson's disease improve after performance of antiparkinsonian drug
      titration within the setting of a specialised Parkinson's disease clinic. The
      effect on symptoms was seen most clearly with the UPDRS, although both peg
      insertion and tapping reflected this improvement to a certain extent. Drug
      titration resulted in, on average, a doubling of daily drug costs. Future trials
      are needed to investigate the long-term effects of such a hospital stay on
      indirect costs associated with treating Parkinson's disease, and on caregiver
      burden, and also to compare the efficacy of a Parkinson's disease clinic with an
      outpatient setting.

PMID- 14728058
TI  - Long-acting risperidone: a review of its use in schizophrenia.
AB  - Long-acting risperidone (Risperdal Consta) is a novel, intramuscular formulation
      of the atypical antipsychotic risperidone, which has shown efficacy in the
      treatment of patients with schizophrenia.Long-acting risperidone is
      pharmacokinetically equivalent to and causes less plasma drug concentration
      fluctuation than the oral formulation. This novel formulation is an aqueous
      suspension of microspheres comprising risperidone and a biodegradable copolymer.
      Significant release of risperidone from the microspheres begins 3 weeks after the
      first injection: thus, administration of another antipsychotic is necessary
      during this period only. Steady-state plasma concentrations are reached after the
      fourth injection. Elimination is complete 7-8 weeks after the last injection.Long
      acting risperidone 25 or 50mg every 2 weeks demonstrated significantly greater
      antipsychotic efficacy than placebo and equivalent efficacy to oral risperidone 2
      6 mg/day in two randomised, double-blind, double-dummy, 12-week trials of
      patients with schizophrenia. Additionally, in one of these trials, improvements
      in health-related quality of life (HRQOL) were superior with long-acting
      risperidone than placebo. Compared with baseline, improvements in the symptoms of
      schizophrenia in stable patients were significant with long-acting risperidone 25
      or 50mg (12-month trial) and 25, 37.5 or 50mg (12-week trial) every 2 weeks, in
      two noncomparative, multicentre trials. Patient satisfaction with their
      medication and patient HRQOL mental health scores improved significantly in the
      12-month trial.Long-acting risperidone is generally well tolerated, with a low
      incidence of injection site pain and an otherwise similar profile of adverse
      effects to the oral formulation. The overall incidence of extrapyramidal
      disorders in clinical trials was low (< or= 10%) with similar, yet minimal,
      changes in extrapyramidal symptom severity between patients treated with long
      acting risperidone, oral risperidone or placebo. Tardive dyskinesia was reported
      in the 12-month trial, in 0.7% of patients. CONCLUSIONS: Long-acting risperidone
      is effective and generally well tolerated in patients with schizophrenia,
      including those patients with stable symptoms. Long-acting risperidone is the
      first atypical antipsychotic available in a formulation which offers a sustained,
      steady release of drug and is thus an attractive, new option in the treatment of
      patients with schizophrenia.

PMID- 14728059
TI  - Therapeutic potential of renin inhibitors in the management of cardiovascular
      disorders.
AB  - The renin-angiotensin system (RAS) is well recognized for its importance in
      regulation of BP, electrolyte balance and vascular growth. Pharmacological
      suppression of the RAS, through ACE inhibition and/or angiotensin receptor
      blockade, is a proven effective therapeutic approach to the treatment of a range
      of cardiovascular diseases. Renin is the enzyme that catalyzes the first and rate
      limiting step of RAS, the cleavage of angiotensinogen to angiotensin I (A-I). A-I
      is then further converted by ACE to the biologically active vasoconstrictor, A
      II. Interruption of the generation of A-II by renin inhibitors at this highly
      specific initial step of the cascade would be expected to have similar but not
      identical effects to those of the already well established RAS antagonists. Due
      to the lack of effective alternative enzyme pathways, blockade of A-II production
      may be more effective with renin inhibition than with ACE inhibition, and because
      of the high specificity of renin for only one substrate, namely angiotensinogen,
      adverse effects would be expected to be less frequent. It is currently unclear
      whether blockade of angiotensin II type 1 receptors (AT(1)), leaving other A-II
      receptors unblocked, is preferable to the reduction in plasma and tissue A-II
      levels achieved with either ACE or renin inhibition. The development of early
      peptidic and peptidomimetic renin inhibitors was hampered by problems with oral
      bioavailability and high costs of synthesis. However recent work has led to the
      synthesis of a potent non-peptidic inhibitor of renin, aliskiren, which has
      acceptable oral bioavailability. This renin inhibitor has been shown to
      effectively reduce A-II levels in normal volunteers and to lower BP in patients
      with mild to moderate hypertension. It appears likely that aliskiren is the first
      of a new class of agents that may prove useful in the management of patients with
      nephropathy, heart failure and atherosclerosis in addition to hypertension.

PMID- 14728060
TI  - Contrast nephropathy : an evidence-based approach to prevention.
AB  - Contrast-induced nephropathy occurs in 2-10% of patients exposed to intravascular
      radiographic contrast agents and results in significant morbidity and mortality.
      Although the exact mechanism of this disorder has not been fully elucidated,
      contrast nephropathy is probably due to a combination of decreased renal
      medullary blood flow, resulting in medullary ischemia, and direct toxicity to
      renal tubules. Contrast nephropathy is most commonly defined as either a >25%
      increase or a >0.5 mg/dL rise in serum creatinine level within 48 hours of
      contrast medium exposure. Baseline characteristics associated with an increased
      risk for development of contrast nephropathy include the presence of baseline
      renal dysfunction, diabetes mellitus, congestive heart failure, volume depletion,
      and concomitant administration of nephrotoxic drugs. Many strategies have been
      investigated in an effort to prevent the occurrence of renal dysfunction
      following contrast media exposure. Intravenous hydration has been shown to
      significantly decrease the incidence of nephropathy in high-risk patients.
      However, trials of several prophylactic pharmacologic interventions have been
      mostly disappointing, including the administration of calcium channel
      antagonists, diuretics, dopamine, endothelin receptor antagonists and fenoldopam.
      The use of N-acetylcysteine has been shown in some trials to decrease the
      incidence of contrast nephropathy in patients with a baseline renal dysfunction,
      and should currently be strongly considered in this high-risk patient subgroup in
      addition to hydration. Our purpose is to review the contemporary literature
      regarding contrast-induced renal dysfunction and present an evidence-based
      approach for prevention of this complication.

PMID- 14728061
TI  - Cancer of the heart: epidemiology and management of primary tumors and
      metastases.
AB  - Cardiac tumors, benign or malignant, are rare and most are benign. The most
      common benign tumor is the cardiac myxoma. Malignant cardiac tumors are usually
      sarcomas. The pericardium can be the site of benign and malignant cardiac tumors,
      though metastatic tumors occur here far more commonly than do primary tumors.
      Successful treatment for benign cardiac tumors is usually achieved by surgical
      resection. Surgery for primary malignant tumors is, however, much less successful
      as complete resection is usually not possible. Primary cardiac lymphoma may be
      successfully treated by chemotherapy. Tumors that metastasize to the heart from
      other organs occur 100- to 1000-fold more commonly than primary cardiac tumors.
      Metastatic spread to the heart has been identified in approximately one-fifth of
      all patients who have metastatic cancer with lung carcinoma being the most common
      primary tumor. Symptoms of cardiac metastases vary, and they depend on the site
      and extent of the lesions. Treatment varies depending on the pathology of the
      primary tumor. However, the aim of treatment is usually symptomatic relief. With
      the advent of AIDS, Kaposi's sarcoma and high grade B cell lymphomas have also
      been identified in cardiac tissue. The aim of this article is to review the
      epidemiology, clinical presentation, pathology and treatment of cardiac tumors.

PMID- 14728056
TI  - Drug-induced myoclonus: frequency, mechanisms and management.
AB  - Myoclonus is a sudden, abrupt, brief, 'shock-like' involuntary movement caused by
      muscular contractions ('positive myoclonus') or a sudden brief lapse of muscle
      contraction in active postural muscles ('negative myoclonus' or 'asterixis').
      Various disorders can cause myoclonus including neurodegenerative and systemic
      metabolic disorders and CNS infections. In addition, myoclonus has been described
      as an adverse effect of some drugs. Level II evidence is available to indicate
      that levodopa, cyclic antidepressants and bismuth salts can cause myoclonus,
      while there is less robust evidence to associate numerous other drugs with the
      induction of myoclonus. The pharmacological mechanisms responsible for this
      adverse effect are not well established, although increased serotonergic
      transmission may be involved in the induction of myoclonus by several drugs. Drug
      induced myoclonus usually resolves after withdrawal of the offending drug, but in
      some cases specific treatments are needed.

PMID- 14728062
TI  - Glycoprotein IIb/IIIa receptor antagonists: a comparative review of their use in
      percutaneous coronary intervention.
AB  - Antiplatelet therapy is critical during percutaneous coronary intervention (PCI)
      as it reduces the incidence of abrupt closure and distal thrombi embolization,
      which are significant acute peri-procedural complications likely responsible for
      the clinical adverse outcomes with PCI, namely death, myocardial infarction or
      urgent target vessel revascularization. Glycoprotein (GP) IIb/IIIa receptor
      antagonists, potent antiplatelet agents, have been specifically tested during
      PCI. There are currently three commercially available GP IIb/IIIa receptor
      antagonists and results from more than ten randomized clinical PCI trials have
      established their clinical efficacy and tolerability during coronary
      intervention. There remain questions regarding variability in efficacy among
      individual clinical trials and among population subsets, potential clinical
      differences among the available agents, and their optimal use. This article will
      critically review the body of evidence for clinical efficacy and tolerability of
      each individual tested compound, highlight potential differences among agents,
      and raise important issues involving their use in clinical practice.

PMID- 14728064
TI  - Hyperuricemia and adverse outcomes in cardiovascular disease: potential for
      therapeutic intervention.
AB  - High uric acid levels are associated with increased morbidity and mortality rates
      in cardiovascular disease. In this article we explore the relationship between
      cardiovascular disease and xanthine oxidase activity. We look at the evidence
      that uric acid and its production via the xanthine oxidase pathway, may directly
      contribute to this increased cardiovascular risk. We examine the relationship
      between uric acid and other established cardiovascular risk factors and look at
      the evidence that reducing uric acid production may have a beneficial impact on
      cardiovascular morbidity and mortality. We conclude that although there is
      currently insufficient evidence to recommend the routine use of xanthine oxidase
      inhibitors in those with cardiovascular disease and asymptomatic hyperuricemia,
      there is sufficient evidence to warrant a large scale morbidity and mortality
      trial.

PMID- 14728063
TI  - Factors influencing family physician adherence to hypertension treatment
      guideline recommendations on the initiation of pharmacotherapy: questionnaire
      survey.
AB  - BACKGROUND: Family physicians do not prescribe antihypertensive medication
      according to current guidelines. This study investigates possible reasons for
      this. The objectives were to measure the knowledge, attitude and stated practice
      of family physicians to the initiation of pharmacotherapy for uncomplicated
      hypertension and to explore the reasons why clinical practice differs from
      guideline recommendations. STUDY DESIGN: A cross-sectional postal survey
      conducted between June and October 1999. Simple frequency analysis and a chi(2)
      test comparing family physician characteristics and responses. METHODS: A three
      phase postal survey was undertaken of a random sample of family physicians.
      Telephone and facsimile contact was made to non-responders. The survey instrument
      included respondent characteristics, preference for initiation of
      antihypertensive drug therapy and their opinion of efficacy, adverse effects and
      long-term safety, as well as knowledge of guidelines. PARTICIPANTS: Family
      physicians in the state of Victoria, Australia. MAIN OUTCOME MEASURES AND
      RESULTS: Ranked preference of drugs for uncomplicated hypertension. Opinion of
      drug efficacy, adverse effects, safety and cost. Knowledge of guidelines for
      first-line antihypertensive drugs. Newer agents are preferred to older agents in
      the initiation of antihypertensive drug therapy contrary to current guideline
      recommendations. Newer agents were thought to be more efficacious, have better
      short- and long-term adverse effect profiles and be more expensive than older
      agents. Younger doctors most often held these attitudes. Guidelines influenced
      decision making but were not the most important factor. CONCLUSIONS: There is a
      demonstrable need for governments to invest in the promotion of accurate
      information on drugs through continuing education of prescribers and facilitating
      the production of standardized paper and web-based clinical guidelines. A program
      of targeted investment in clinical trials that examine the justification for more
      expensive classes of agents should also be considered in appropriate
      circumstances.

PMID- 14728065
TI  - Clinical potential of advanced glycation end-product inhibitors in diabetes
      mellitus.
AB  - Non-enzymatic accumulation of advanced glycation end-products (AGE) is to some
      extent a physiologic consequence of tissue aging. On the other hand, circulating
      AGE and tissue deposits mark the course of diabetes mellitus as well as a variety
      of other vascular or degenerative diseases. AGE generation is paralleled by
      oxidative damage and lipid peroxidation within target tissue, with features of
      inflammation through the involvement of monocytes/macrophages expressing
      receptors for glycated macromolecules. Over the past 15 years, a wealth of data
      concerning the pharmacology of AGE have been gathered through animal and human
      investigations, targeting their likely contribution to the progression of
      diabetic and non-diabetic vascular damage. Several agents have been shown to
      interfere with the formation of AGE or AGE precursors, bind to tissue receptors,
      or promote breakdown of deposits. The first and most studied inhibitor,
      aminoguanidine, has shown extensive beneficial effects in experimental models of
      diabetic vascular damage, recently entering phase I-III clinical investigation.
      Newer anti-AGE agents include pyridoxamine and the so-called 'amadorins', cross
      link breakers, AGE binders and receptor antagonists.

PMID- 14728066
TI  - Immunosuppressive therapy for heart failure: a guide to patient selection.
AB  - Therapy with beta-adrenoceptor antagonists, ACE inhibitors and most recently,
      spironolactone was established for reducing all-cause mortality in patients with
      congestive heart failure (CHF), improving patient clinical status and inhibiting
      the disease progression. Unfortunately, despite optimal therapy for CHF in some
      patients, the disease progresses and, as yet, no conclusive mechanism has been
      identified for deterioration of cardiac function in patients with heart failure.
      Defining the cause of CHF in patients with dilated cardiomyopathy may have
      prognostic and therapeutic implications. Clinical and experimental evidence
      suggests that long-term inflammation may play a key part in the development of
      heart failure in patients with cardiomyopathy due to ischemic heart disease and
      those with cardiomyopathy due to non-ischemic cases. Because chronic immune
      myocardial injury, found in patients with CHF is myocardial restricted,
      endomyocardial biopsy with immunohistological markers of immune-mediated injury
      may offer us new guidelines to patient selection for immunomodulatory therapies.
      Few randomized placebo controlled studies addressing the effectiveness of
      suppression and modulation of the immune system in patients with heart failure
      gave unequivocal results. Moreover, none of the abovementioned randomized studies
      has shown decreased mortality in the immunosuppressively treated patients
      compared with conventionally treated patients. In the US Myocarditis Treatment
      Trial, for example, mortality was 20% overall at 1 year and 56% at 4.3 years of
      follow-up. In addition, spontaneous improvement of left ventricular systolic
      function has been reported in 30-40% of conventionally treated patients with CHF
      due to dilated cardiomyopathy. Given the high proportion of patients who improve
      spontaneously, selection of patients for immunosuppressive therapy should be
      preceded by treating heart failure with the individualized conventional therapy
      (ACE inhibitors, beta-adrenoceptor antagonists, spironolactone) for at least 6
      months. Final decision to use immunomodulatory therapies should be based on
      comprehensive clinical measures of disease progression.

PMID- 14728067
TI  - The role of lipids in the development of diabetic microvascular complications:
      implications for therapy.
AB  - Dyslipidemia is a major factor responsible for coronary heart disease and its
      reduction decreases coronary risk in patients with diabetes mellitus. However,
      the association of dyslipidemia with microvascular complications and the effect
      of intervention with lipid-lowering therapy in diabetes have been less
      investigated. We present the systematic review of association and intervention
      studies pertaining to dyslipidemia and microvascular disease in diabetes and also
      review possible mechanisms. Dyslipidemia may cause or exacerbate diabetic
      retinopathy and nephropathy by alterations in the coagulation-fibrinolytic
      system, changes in membrane permeability, damage to endothelial cells and
      increased atherosclerosis. Hyperlipidemia is associated with faster decline in
      glomerular filtration rate and progression of albuminuria and nephropathy. Recent
      evidence also suggests a role of lipoprotein(a) in progression of retinopathy and
      nephropathy in patients with diabetes mellitus. Lipid-lowering therapy, using
      single agents or a combination of drugs may significantly benefit diabetic
      retinopathy and diabetic nephropathy. In particular, hydroxymethyl glutaryl
      coenzyme A reductase inhibitors may be effective in preventing or retarding the
      progression of microvascular complications because of their powerful lipid
      lowering effects and other additional mechanisms. However, most of the data are
      based on short-term studies, and need to be ascertained in long-term studies.
      Until more specific guidelines are available, aggressive management of diabetic
      dyslipidemia, according to currently accepted guidelines, should be continued for
      the prevention of macrovascular disease which would also benefit microvascular
      complications.

PMID- 14728068
TI  - Smoking cessation for patients with cardiovascular disease: what is the best
      approach?
AB  - Tobacco use remains the major preventable cause of early mortality and morbidity
      in the US and is a major risk factor for cardiovascular disease (CVD). Quitting
      smoking rapidly reduces the risk of cardiovascular events. In this review, we
      identify and discuss best approaches to assist smoking cessation among patients
      with CVD. Establishing office systems that reliably identify smokers to
      healthcare providers is an essential first step. Once the patient is identified
      as a smoker, providers should inquire about their willingness to quit and advise
      them to quit or provide motivation to get ready to make a quit attempt.
      Behavioral (counseling) and pharmacologic (nicotine replacement and non-nicotine
      medications) treatments double or triple long-term cessation rates and should be
      offered in combination to all patients with CVD who use tobacco. More intensive
      behavioral therapy is more effective and should be delivered when possible. The
      choice of pharmacotherapy will depend upon the clinical history of the patient
      and patient preference. Nicotine replacement and sustained release bupropion
      (bupropion SR) are first-line treatments for smoking cessation. Nicotine patches
      have been studied extensively in patients with stable CVD and have been shown to
      be safe. Bupropion SR has relatively few cardiovascular adverse effects and may
      be especially useful for patients with CVD; its safety is currently being
      studied. Special consideration is needed for hospitalized patients with acute
      coronary syndromes (e.g. myocardial infarction and unstable angina). The safety
      of pharmacotherapy in the acute setting is not yet established. Behavioral
      interventions, however, are very effective and should be delivered to all
      hospitalized smokers. Finally, it is important to create a clinical environment
      that is supportive of treating patients with tobacco dependence. Simple changes
      in office and hospital routines and procedures (routine screening to identify
      smokers, prompts to encourage intervention and links to more intensive tobacco
      dependence treatment programs) will substantially improve the identification,
      treatment, and outcomes of patients with CVD who use tobacco.

PMID- 14728069
TI  - ACE Inhibition with moexipril: a review of potential effects beyond blood
      pressure control.
AB  - ACE inhibitors induce metabolic changes and exert cardioprotective and
      vasoprotective properties, some of which cannot be attributed to their
      antihypertensive effect per se. Moexipril is an ACE inhibitor with a
      lipophilicity in the same range as quinapril, benazepril or ramipril, and so can
      readily penetrate lipid membranes and thus target tissue ACE in addition to
      plasma ACE. Evidence from animal studies shows similar and significant (p < 0.05)
      reductions in tissue ACE activity for moexipril and quinapril. Moexipril may
      improve endothelial dysfunction; moexiprilat and ramiprilat have demonstrated
      greater activity than captopril, enalaprilat and quinaprilat in isolated
      endothelium-denuded segments of the rabbit jugular vein where bradykinin elicits
      a constrictor response, mediated by activation of the bradykinin B(2) receptor.
      ACE inhibitors, including moexipril, may exert neuroprotective effects. Moexipril
      promoted neuronal survival in vitro and it is thought that this neuroprotective
      effect is due to free radical scavenging properties of the drug. ACE inhibitors
      can also decrease progression of renal insufficiency in patients with various
      underlying renal diseases. Moexipril may also have a renoprotective effect as it
      increased the ultrafiltration coefficient and normalized urinary protein
      excretion in rat models. Preclinical studies indicate that the renin-angiotensin
      aldosterone system may play a role in the regulation of bone resorption and
      moexipril had no adverse effects on bone metabolism in animal models and the drug
      did not hamper the osteoprotective effects of estrogen. Reduction in left
      ventricular mass with moexipril in patients with hypertension was similar in
      magnitude to the effect of other ACE inhibitors. When investigated in
      hypertensive patients with an elevated cardiovascular risk, moexipril increased
      arterial distensibility and demonstrated antioxidative properties in addition to
      efficiently controlling blood pressure. Moexipril does not adversely affect serum
      levels of uric acid, lipids, blood glucose levels and plasma insulin levels and
      can be co-administered with hormone replacement therapy. Moreover, quality-of
      life data suggest favorable effects of moexipril treatment in a patient
      population at high cardiovascular risk.

PMID- 14728070
TI  - Assessment of anti-ischemic and antianginal effect at trough plasma concentration
      and safety of trimetazidine MR 35 mg in patients with stable angina pectoris: a
      multicenter, double-blind, placebo-controlled study.
AB  - OBJECTIVE: The study aimed to assess, at trough plasma concentration, the anti
      ischemic and antianginal efficacy and tolerability of trimetazidine modified
      release (MR) 35 mg taken twice daily by patients with stable angina pectoris.
      DESIGN: This multicenter, randomized, double-blind, placebo-controlled,
      international study started with a run-in period of 3 weeks with atenolol 50
      mg/day and placebo, followed by a 6-month treatment period with once daily
      atenolol 50 mg and twice daily trimetazidine MR 35 mg or placebo. PATIENTS: The
      study involved 223 patients with stable angina pectoris (class II or III of the
      Canadian Cardiovascular Society [CCS] classification). 180 patients were analyzed
      in the full analysis set (FAS) following the intention to treat principle (ITT)
      and 167 patients were analyzed in the per protocol set (PPS). The PPS data are
      presented here. INTERVENTIONS: Two exercise tolerance tests (ETTs) were performed
      during the run-in period in order to assess the stability of exercise tolerance
      before angina pectoris and significant ST segment depression. Efficacy was
      assessed by a third ETT performed after 8 weeks of treatment, at trough, 12 hours
      after the intake of the drug. Safety was evaluated over the 6-month duration of
      the study. MAIN OUTCOMES MEASURES: Time to 1 mm ST segment depression. RESULTS:
      Time to 1 mm ST segment depression was increased by 44 seconds more in the
      trimetazidine MR 35 mg group than in the placebo group (p = 0.005). A significant
      difference was also evidenced for the time to onset of angina pectoris (p =
      0.049) and for the reason for stopping the exercise (p = 0.02). No difference
      between groups was found for safety parameters. CONCLUSION: This study
      demonstrates the anti-ischemic and antianginal efficacy of trimetazidine MR 35 mg
      twice daily at trough plasma concentrations in patients with stable angina
      pectoris receiving atenolol 50 mg/day. Furthermore, the drug is well tolerated
      over 6 months.

PMID- 14728071
TI  - Losartan: in the reduction of stroke risk in patients with hypertension and left
      ventricular hypertrophy.
AB  - Losartan binds selectively to the angiotensin II subtype 1 receptor, blocking the
      activity of angiotensin II. Losartan 50-100 mg/day was compared with atenolol 50
      100 mg/day in patients with essential hypertension and left ventricular
      hypertrophy (LVH) [n = 9,193] in the randomized, double-blind Losartan
      Intervention For Endpoint reduction in hypertension (LIFE) study. Two substudies
      compared these drugs in patients with diabetes mellitus (n = 1,195) or isolated
      systolic hypertension (ISH) [n = 1326]. The target BP (<140/90 mm Hg) was
      achieved in approximate, equals 45% of losartan and atenolol recipients in the
      LIFE study. Significant regression of LVH occurred with losartan versus atenolol
      in the LIFE study, as well as in the diabetes mellitus and ISH substudies. In the
      LIFE study, although BP reduction was similar for the two treatments, the risk of
      a cardiovascular event (the composite of cardiovascular death, stroke, and
      myocardial infarction; primary endpoint), stroke, or new-onset diabetes mellitus
      was significantly lower with losartan than with atenolol. Losartan was generally
      well tolerated in patients with hypertension and LVH in the LIFE study.
      Significantly fewer losartan than atenolol recipients discontinued treatment
      because of adverse events, drug-related adverse events, or serious, drug-related
      adverse events.

PMID- 14728075
TI  - Does magnesium have a role in the treatment of patients with coronary artery
      disease?
AB  - Hypomagnesemia is common in hospitalized patients, especially in elderly patients
      with coronary artery disease (CAD) and/or those with chronic heart failure.
      Hypomagnesemia is associated with increased all cause mortality and mortality
      from CAD. Magnesium supplementation improves myocardial metabolism, inhibits
      calcium accumulation and myocardial cell death; it improves vascular tone,
      peripheral vascular resistance, afterload and cardiac output, reduces cardiac
      arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability
      to oxygen-derived free radicals, improves endothelial function and inhibits
      platelet function, including platelet aggregation and adhesion, which potentially
      confers upon magnesium physiologic and natural effects similar to adenosine
      diphosphate inhibitors such as clopidogrel. However, data regarding the use of
      magnesium in patients with acute myocardial infarction (AMI) are conflicting.
      Although some previous relatively small randomized clinical trials demonstrated a
      remarkable reduction in mortality when intravenous magnesium was administered to
      relatively high risk AMI patients, two recently published large-scale randomized
      clinical trials (the Fourth International Study of Infarct Survival [ISIS 4] and
      Magnesium in Coronaries [MAGIC]) were unable to demonstrate any advantage of
      intravenous magnesium over placebo. Nevertheless, the theoretical benefits of
      magnesium supplementation as a cardio-protective agent in CAD patients, promising
      results from animal and human studies, its relatively low-cost and ease of
      handling requiring no special expertise, together with its excellent
      tolerability, gives magnesium a place in treating CAD patients, especially in
      those at high risk, such as CAD patients with heart failure, the elderly and
      hospitalized patients with hypomagnesemia. Furthermore, magnesium therapy is
      indicated in life-threatening ventricular arrhythmias such as torsades de pointes
      and intractable ventricular tachycardia.

PMID- 14728074
TI  - Spotlight on abciximab in patients with ischemic heart disease undergoing
      percutaneous coronary revascularization.
AB  - Abciximab (Reopro) is an antibody fragment that dose-dependently inhibits
      platelet aggregation and leucocyte adhesion by binding to the glycoprotein (GP)
      IIb/IIIa, vitronectin and Mac-1 receptors. Abciximab (0.25 mg/kg bolus plus
      infusion of 0.125 micro g/kg/min for 12 hours) showed greater efficacy than
      tirofiban in reducing the 30-day composite endpoint of death, nonfatal myocardial
      infarction (MI) or urgent target-vessel revascularization in the randomized,
      double-blind TARGET study in patients scheduled for stent placement. In addition,
      the beneficial effects of treatment with abciximab previously observed in the
      randomized, multicenter, placebo-controlled EPILOG and EPISTENT studies have been
      maintained to 1 year, with a significantly reduced incidence of ischemic
      complications relative to placebo consistently observed across a range of
      subgroups including age, sex, bodyweight and indication for revascularization.
      The incidence of the composite endpoint was reduced in patients presenting with
      acute MI of <48 hours' duration in comparison with either fibrinolytic therapy or
      stenting alone in the randomized STOPAMI and ADMIRAL trials, primarily because of
      a reduced requirement for urgent repeat revascularization and reduced incidence
      of mortality. In the randomized, nonblind, multicenter CADILLAC trial in patients
      with acute myocardial infarction (MI), stenting alone was superior to
      percutaneous transluminal coronary angioplasty (PTCA) and stenting alone was not
      inferior to PTCA plus abciximab. Recent large randomized, multicenter studies
      (ASSENT-3 and GUSTO-V) have shown higher efficacy (on various ischemic endpoints)
      of abciximab in combination with either a reduced dose of tenecteplase or
      reteplase compared with the fibrinolytic drug alone. TIMI grade 3 flow rates at
      60 and 90 minutes in the TIMI-14 and SPEED trials were higher in patients who
      received abciximab in combination with either alteplase or reteplase than
      abciximab alone and were similar to that seen with the full-dose fibrinolytic
      alone. In the randomized, multicenter GUSTO IV-ACS study, no significant
      differences in any of the ischemic endpoints at either 7 or 30 days in patients
      with acute coronary syndromes who were not scheduled to undergo early
      revascularization (within 12 hours of end of infusion) were apparent between
      those who received abciximab (bolus and either 24- or 48-hour infusion) and those
      who received placebo in addition to aspirin and heparin. The most common adverse
      events associated with the use of abciximab are bleeding complications and
      thrombocytopenia, although the risk of major bleeding can be limited through
      adhering to current administration protocols. Treatment costs are generally
      higher in both stent plus abciximab and angioplasty plus abciximab groups than
      stent plus placebo, primarily because of the acquisition cost of abciximab.
      Abciximab appeared most cost beneficial in high-risk patients undergoing elective
      percutaneous coronary revascularization; among lower risk patients, abciximab
      therapy has been associated with higher total in-hospital and 6-month medical
      costs than eptifibatide. CONCLUSION: The GP IIb/IIIa receptor antagonist
      abciximab, when used with aspirin and heparin, has demonstrated efficacy in
      reducing the short- and long-term risk of ischemic complications in patients with
      ischemic heart disease undergoing percutaneous coronary intervention, when used
      with aspirin and heparin. High-risk patients (including those with diabetes
      mellitus) derive particular benefits from abciximab treatment. Abciximab remains
      an important therapeutic option for the prevention of complications in patients
      with ischaemic heart disease.

PMID- 14728076
TI  - Could influenza vaccination prevent myocardial infarction, stroke and sudden
      cardiac death?
AB  - Acute myocardial infarction (AMI), sudden cardiac death and atherothrombotic
      stroke, which share a common pathogenesis involving disrupted atherosclerotic
      plaque and intravascular thrombosis, vary seasonally, with peak incidence in
      winter months. This seasonality is similar to that of upper respiratory
      infections, of which 38% are due to influenza. Infections such as influenza
      produce many biochemical, cellular, and hemostatic changes that could predispose
      to plaque disruption and thrombosis. Infections, particularly of the respiratory
      tract, often precede AMI and stroke. Four observational studies and one small
      clinical trial suggest that influenza vaccination can reduce the occurrence of
      sudden death, AMI, and stroke by approximately 50%. Influenza vaccine is very
      well-tolerated. With up to 16% of adults contracting influenza each year and the
      vaccine reducing the incidence of influenza by 50%, influenza vaccination could
      make a substantial public health impact on acute cardiac and neurovascular
      events.

PMID- 14728077
TI  - Prevention of cardiac cell injury during acute myocardial infarction: possible
      role for complement inhibition.
AB  - The purpose of this article is to describe mechanisms of cell death in patients
      with acute myocardial infarction, particularly the activation of the complement
      system. Various pro-inflammatory cytokines, released by the inflamed tissue, play
      a role in the activation of the complement system. Several complement inhibitors
      have been developed to reduce tissue damage following ischemia. According to
      animal studies the deleterious effects of activators of the complement system can
      be diminished by complement inhibition. Several clinical studies have been
      conducted for the potential treatment of cell injury during acute myocardial
      infarction. C1 inhibitor dose-dependently inhibited complement activation and
      appeared to reduce myocardial injury after reperfusion therapy in patients with
      acute myocardial infarction. C1 inhibitor dose-dependently reduced plasma levels
      of C4 activation fragments. In addition, cardiac enzymes (troponin T and creatine
      kinase-MB) returned to baseline levels more rapidly among patients treated with
      C1 inhibitor, compared with controls. Furthermore, preliminary results from a
      placebo-controlled trial indicate that treatment with intravenous pexelizumab
      (anti-C5 antibody) was well tolerated in a large number of patients undergoing
      coronary artery bypass graft surgery. Further, more randomized trials are
      necessary to clarify the clinical significance of this new and innovative
      treatment with complement inhibition.

PMID- 14728078
TI  - Hyperoxemic perfusion for treatment of reperfusion microvascular ischemia in
      patients with myocardial infarction.
AB  - In patients with acute myocardial infarction (AMI) primary angioplasty and stent
      placement is a more effective and better tolerated treatment than thrombolysis,
      and therefore, when logistics allow, this treatment is preferred and routinely
      used. However, successful reopening of an occluded coronary artery does not
      necessarily lead to recovery of left ventricular (LV) function. Post-AMI
      reduction in contractile function and ventricular remodeling may result in heart
      failure. There is evidence that reduced contractile function in the infarct zone
      is related to poor microvascular perfusion even after normalization of large
      vessel flow by angiographic criteria following coronary recanalization. Failure
      to re-establish adequate tissue perfusion may be because of reperfusion injury,
      ischemia-induced microvascular damage, and plugging of the microcirculation by
      thrombus and plaque during mechanical recanalization. Experimental data support
      the hypothesis that reperfusion microvascular ischemia contributes to myocardial
      tissue injury over a prolonged time period. Hyperbaric oxygen therapy (HBO)
      attenuates microvascular dysfunction and reperfusion microvascular ischemia, as
      demonstrated in both experimental models and patients with AMI. However, treating
      patients in an HBO chamber or with a conventional oxygenator is impractical and
      difficult. Aqueous oxygen (AO) is a newly developed solution containing extremely
      high oxygen concentrations (1-3 ml O(2)/mL saline). The AO system mixes AO
      solution with a patient's blood from an arterial puncture and delivers the
      hyperoxemic blood to targeted ischemic myocardium via an infusion catheter for
      regional correction of hypoxemia and production of hyperoxemia. The system
      precisely controls the level of pO(2) without clinically significant microbubble
      formation. Hyperoxemic coronary infusion of AO in experimental models of AMI
      improved LV function and reduced infarct size compared with normoxemic
      controls,very likely as a result of microvascular blood flow improvement. The
      first clinical experiences with intracoronary infusion of AO solution
      demonstrated the therapy to be a safe and well tolerated in the setting of AMI
      after successful primary percutaneous transluminal coronary angioplasty. Its use
      was associated with significant progressive improvement in LV function as
      measured by ejection fraction and wall motion score index. Interestingly, such
      improvement was primarily due to functional recovery of infarct zone
      contractility. A larger randomized trial is currently underway to define the role
      of hyperoxemic coronary infusion in patients with AMI.

PMID- 14728079
TI  - Treatment of cardiac arrest with automatic external defibrillators: impact on
      outcome.
AB  - Sudden cardiac death is the leading cause of death in the US and most developed
      nations. Ventricular fibrillation (VF) is the most common initial rhythm in
      survivors of cardiac arrest. The most important factor in determining survival
      from VF is the time from collapse to administration of the first defibrillation
      shock. Automatic external defibrillators (AEDs) have been developed and widely
      deployed in an attempt to reduce the time to defibrillation. Data on early
      defibrillation using AEDs has led to a number of public access defibrillator
      placements in the US and ongoing studies of public access AED use. The safety of
      lay person AED use is clear. Clearly some concentrated captive populations (e.g.
      airports, airplanes) may benefit from public access AEDs. Therefore, widespread
      AED education as a means of increasing public acceptance of lay person AED use
      must be a priority. As technology evolves costs will decline, however, the
      current economic reality requires careful consideration of the cost effectiveness
      of specific AED placement.

PMID- 14728080
TI  - Reduction of serum LDL-C levels: a relationship to clinical benefits.
AB  - The association between elevated serum cholesterol levels and cardiovascular risk
      was established several decades ago by studies such as the Framingham study and
      the Multiple Risk Factor Intervention Trial (MRFIT). Both primary and secondary
      prevention trials of cholesterol lowering, using HMG-CoA reductase inhibitors,
      have demonstrated clear benefits for lipid lowering in preventing both
      cardiovascular morbidity and mortality over a wide spectrum of coronary heart
      disease (CHD) risk. Even so, risk of events has been reduced by about 30% in
      these trials, leaving 70% of events occurring even in the presence of substantial
      cholesterol lowering. It is unknown whether further reduction of serum
      cholesterol levels will lower risk factors. The relationship between cholesterol
      lowering and cardiovascular risk, moreover, is not completely defined; it is
      unclear, at lower cholesterol levels, whether that relationship follows a
      threshold, a linear, or a curvilinear model. Early studies of low-density
      lipoprotein-cholesterol (LDL-C) lowering with HMG-CoA reductase inhibitors
      suggested that non-cardiovascular mortality might be increased at low serum LDL-C
      levels, however, these concerns have not been supported by subsequent clinical
      trials. Recent studies have shed further light on the potential benefits of
      lowering serum cholesterol levels beyond current guideline targets with HMG-CoA
      reductase inhibitors. More potent agents in development are likely to make such
      levels more readily achievable, as well as making guideline targets attainable
      for many of the large number of patients who currently fail to reach them.

PMID- 14728081
TI  - Preventing macrovascular disease in patients with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (DM) is associated with an increased risk for both micro
      and macrovascular complications, and cardiovascular diseases (CVD) are the most
      common causes of death in these patients, accounting for almost 70% of the
      deaths. Given the high prevalence of the condition and the expected global
      increase in the prevalence of type 2 DM, a case is made for prevention of these
      serious complications in order to reduce the individual morbidity and the
      economic burden on society. In this review we present the knowledge of how
      macrovascular disease in patients with type 2 DM may be prevented, and suggest
      possible strategies for doing so.A thorough search of the published literature
      was conducted and we first present relevant epidemiological studies demonstrating
      the impact of important risk factors for CVD in DM, such as dyslipidemia,
      hyperglycemia, hypertension, smoking, familial premature coronary heart disease
      and some non-classical risk factors such as hyperinsulinemia, insulin resistance,
      endothelial dysfunction and inflammation. Secondly, we review the results from
      published randomized controlled clinical trials and meta-analysis of these,
      evaluate the findings and suggest strategies for preventing CVD in patients with
      type 2 DM using non-pharmacological and pharmacological approaches. Present
      knowledge indicates that most patients with type 2 DM either have manifest CVD or
      have a high risk for future cardiovascular events, men with DM have a 2- to 4
      fold; and women with DM a 3- to 5-fold increased risk for cardiovascular death
      compared with non-diabetic individuals. Care of patients with type 2 DM should
      include yearly risk assessment by the use of published risk equations or risk
      charts. On the background of this assessment, an individual risk reducing
      strategy should be tailored to each patient's need, including the treatment of
      hyperglycemia, hypertension and dyslipidemia together with the use of aspirin
      (acetylsalicylic acid) and ACE inhibitors. Such measures can reduce the risk of
      cardiovascular events in patients with type 2 DM.

PMID- 14728083
TI  - Introduction. Ziprasidone in schizophrenia: from acute treatment to long-term
      management.

PMID- 14728084
TI  - The psychopharmacology of ziprasidone: receptor-binding properties and real-world
      psychiatric practice.
AB  - Schizophrenia is a highly complex disorder characterized by a diversity of
      symptoms, psychotic and nonpsychotic, that most likely arise from heterogeneous
      neuroanatomical and neurochemical malfunctions. As with all antipsychotic agents,
      ziprasidone targets the key hypothetical neurochemical disturbance in psychosis
      excessive dopamine neurotransmission at dopamine D2 receptors in the mesolimbic
      pathway of the brain-presumably responsible for the positive symptoms of
      schizophrenia. Like other atypical antipsychotic agents, ziprasidone is a
      serotonin-2A (5-HT2A)/dopamine D2 antagonist; however, its in vitro 5-HT2A/D2
      receptor affinity ratio is higher than that of the other first-line atypical
      antipsychotic agents (namely, risperidone, olanzapine, quetiapine, and
      aripiprazole). Ziprasidone also exhibits potent interaction with 5-HT2C, 5-HT1D,
      and 5-HT1A receptors in human brain tissue, characteristics that predict
      heightened negative symptom relief, enhanced modulation of mood, cognitive
      improvement, and reduced motor dysfunction. Ziprasidone has moderate affinity for
      serotonin and norepinephrine reuptake sites, predicting antidepressant/anxiolytic
      activity. On the other hand, ziprasidone's low affinity for alpha1-adrenoceptors,
      as well as histamine H1 and muscarinic M1 receptors, suggests that patients
      should experience relatively little orthostatic hypotension, sedation, cognitive
      disturbance, weight gain, or dysregulation of prolactin levels. Efficacy and
      tolerability data from trials to date indicate that ziprasidone's clinical
      activity is consistent with its receptor profile.

PMID- 14728085
TI  - Intramuscular ziprasidone: moving beyond the conventional in the treatment of
      acute agitation in schizophrenia.
AB  - The appropriate management of schizophrenia and schizoaffective disorder requires
      effective, safe antipsychotic agents for use across a continuum of treatment,
      from control of acute psychotic episodes to prevention of relapse. Intramuscular
      (IM) formulations are the method of choice for administering antipsychotics to
      schizophrenic patients who require emergency treatment but cannot take oral
      medication. Atypical antipsychotics are now widely acknowledged as the first-line
      choice for the management of patients with schizophrenia. However, use of these
      agents in acutely agitated psychotic patients has been limited by the lack of an
      IM formulation. Ziprasidone is the first, and currently only, atypical
      antipsychotic to be available in a rapid-acting IM formulation. This review
      focuses on studies evaluating the efficacy and tolerability of IM ziprasidone. In
      agitated psychotic patients, IM ziprasidone reduces agitation as early as 15
      minutes after administration, with improvement sustained for > or = 4 hours. In
      patients with acute psychosis, with or without agitation, IM ziprasidone has been
      demonstrated to be superior to IM haloperidol in improving overall symptom
      severity. During the critical IM-to-oral transition, efficacy and tolerability
      are maintained with ziprasidone. IM ziprasidone represents an important advance
      over older, conventional IM agents in the treatment of the acutely ill patient
      with schizophrenia.

PMID- 14728086
TI  - Oral ziprasidone in the treatment of schizophrenia: a review of short-term
      trials.
AB  - Pharmacotherapy of schizophrenia presents a set of challenges. Ideally,
      antipsychotic therapy should have a rapid effect on clinical improvement, show
      effectiveness against symptoms in multiple domains, and possess a tolerability
      profile that optimizes patient adherence and overall health outcomes. The
      atypical antipsychotic ziprasidone has been shown in placebo- and active
      comparator-controlled clinical studies to be effective in treating the positive,
      negative, and affective symptoms of schizophrenia. In placebo-controlled trials
      of 4 to 6 weeks, significant improvements in overall psychopathology and negative
      symptoms as early as 1 week after treatment initiation were demonstrated. In
      trials of 4 to 8 weeks' duration in patients with acute exacerbation of
      schizophrenia, ziprasidone demonstrated efficacy comparable to that of
      haloperidol, olanzapine, and risperidone. In a 12-week study of patients with
      treatment-resistant schizophrenia, ziprasidone demonstrated overall efficacy
      comparable to that of chlorpromazine, with superior improvement in negative
      symptoms. In 6-week, open-label switching studies, patients switched to
      ziprasidone from conventional antipsychotics, olanzapine, or risperidone because
      of suboptimal efficacy or tolerability experienced improvement in symptoms. Oral
      ziprasidone's tolerability profile includes a lower movement disorder burden than
      that of risperidone, a lower liability for weight gain than that of risperidone
      or olanzapine, and an absence of significant deleterious effects on serum lipid
      levels or glucose metabolism. Available clinical data support rapid titration to
      > or = 120 mg/day for optimal efficacy in patients with acute exacerbation of
      schizophrenia.

PMID- 14728087
TI  - Maintaining symptom control: review of ziprasidone long-term efficacy data.
AB  - Reducing the risk of relapse and maintaining symptom control are core goals in
      the long-term treatment of patients with schizophrenia or schizoaffective
      disorder because symptom control can allow patients and clinicians to focus on
      functional improvement. The atypical antipsychotic agents have gained widespread
      acceptance in this setting because they are at least as effective as the
      conventional antipsychotic agents, may offer an advantage in relapse prevention,
      and offer safety advantages, primarily a reduced liability for movement
      disorders. However, there are differences among the atypical agents that may
      affect both clinician choice and patient adherence to long-term therapy.
      Ziprasidone has shown long-term antipsychotic efficacy in comparisons with
      haloperidol, olanzapine, and risperidone, as well as efficacy in patients
      switched from another antipsychotic agent. This review examines symptom efficacy
      data for ziprasidone in long-term trials that lasted between 28 and 52 weeks.
      Antipsychotic medication is the foundation of long-term treatment of
      schizophrenia. Optimization of treatment for the individual patient requires
      consideration of symptom control, prevention of relapse, and possible long-term
      health consequences. Clinical trial data on ziprasidone's long-term efficacy
      provide a firm basis for selection of this agent.

PMID- 14728088
TI  - Ziprasidone and cognition: the evolving story.
AB  - Cognitive impairment, a central characteristic of schizophrenia, can profoundly
      limit patients' ability to acquire or maintain skills needed for adequate
      functioning. Thus, research on the efficacy of antipsychotic medications is
      increasingly focusing on the possible benefits of these agents on cognitive
      function. Although data are limited, it appears that atypical antipsychotics
      consistently improve cognitive function to a greater extent than do older,
      conventional agents. This review focuses on the atypical agent ziprasidone and
      its effects on cognitive function. The most recent data on the cognitive effects
      of ziprasidone come from a comparative trial with olanzapine (40-80 mg b.i.d. and
      5-15 mg q.d., respectively) and from 3 studies in which patients were switched to
      ziprasidone (40-160 mg/day) because of suboptimal efficacy or tolerability with
      other antipsychotics. In general, ziprasidone-treated patients demonstrated
      significant improvements in multiple cognitive domains--such as episodic memory,
      attention/vigilance, executive function, and visuomotor speed--that are generally
      associated with improved functional outcome. In the switching studies, path
      analysis indicated that improvement on the Positive and Negative Syndrome Scale
      (PANSS) cognitive subscale directly affected changes on the PANSS anxiety
      depression cluster and a PANSS "prosocial" subscale composed of items related to
      social engagement. Improvement in cognitive function observed with ziprasidone
      may have implications for long-term patient outcomes.

PMID- 14728089
TI  - Tolerability of ziprasidone: an expanding perspective.
AB  - Although atypical antipsychotic agents have improved the management of patients
      with schizophrenia, their utility has been hindered by some limitations,
      including significant weight gain, glucose metabolism disturbances, and increases
      in total and low-density lipoprotein cholesterol and triglyceride levels. In
      addition to its low liability for movement disorders and its favorable
      tolerability record in short- and long-term clinical trials, ziprasidone is
      associated with a favorable metabolic safety profile (in terms of its effect on
      plasma lipid and glucose levels) and a negligible effect on weight. The limited
      effect of ziprasidone on the corrected QT interval (QTc) has also been well
      characterized, and experience to date has not demonstrated any increased risk of
      clinical events attributable to QTc prolongation. This review of pharmacokinetic
      and clinical trials of ziprasidone versus placebo and active comparators focuses
      on the safety and tolerability of both the intramuscular and oral formulations.

PMID- 14728091
TI  - Posttraumatic stress disorder as a result of mass trauma.
AB  - There is a large body of literature on the psychological consequences of trauma
      experienced by individuals, but there are few studies of the acute and long-term
      effects of mass trauma on victimized communities. Acute stress reactions are
      expected, and overall resilience in the aftermath of major disasters is the rule
      rather than the exception. However, the available literature on mass trauma
      suggests that certain factors may provide clues to identifying persons at greater
      risk for posttraumatic stress disorder (PTSD). The severity of the trauma and the
      accessibility of support systems may affect long-term outcome. In industrialized
      countries, mass violence caused by malicious human intent may be a more virulent
      precursor to PTSD than other types of mass trauma, such as technological or
      natural disasters. School-aged children, women, persons with existing psychiatric
      illness, those who experienced significant losses or threat to life, those who
      have insufficient psychological and social support systems, and persons who
      exhibit symptoms of functional impairment may be at greater risk for PTSD. The
      findings of a population study of 2 traumatized communities are discussed. Early
      intervention in communities suffering mass trauma should consist of general
      support and bolstering of the recovery environment rather than psychological
      treatment; some forms of early psychological interventions may worsen outcome.
      There is a great unmet need for treatment and intervention guidelines for victims
      of mass trauma, and well-designed studies are warranted.

PMID- 14728092
TI  - Structural and functional brain changes in posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a highly disabling condition that is
      associated with intrusive recollections of a traumatic event, hyperarousal,
      avoidance of clues associated with the trauma, and psychological numbing. The
      field of neuroimaging has made tremendous advances in the past decade and has
      contributed greatly to our understanding of the physiology of fear and the
      pathophysiology of PTSD. Neuroimaging studies have demonstrated significant
      neurobiologic changes in PTSD. There appear to be 3 areas of the brain that are
      different in patients with PTSD compared with those in control subjects: the
      hippocampus, the amygdala, and the medial frontal cortex. The amygdala appears to
      be hyperreactive to trauma-related stimuli. The hallmark symptoms of PTSD,
      including exaggerated startle response and flashbacks, may be related to a
      failure of higher brain regions (i.e., the hippocampus and the medial frontal
      cortex) to dampen the exaggerated symptoms of arousal and distress that are
      mediated through the amygdala in response to reminders of the traumatic event.
      The findings of structural and functional neuroimaging studies of PTSD are
      reviewed as they relate to our current understanding of the pathophysiology of
      this disorder.

PMID- 14728093
TI  - Neurobiological consequences of childhood trauma.
AB  - There is considerable evidence to suggest that adverse early-life experiences
      have a profound effect on the developing brain. Neurobiological changes that
      occur in response to untoward early-life stress can lead to lifelong psychiatric
      sequelae. Children who are exposed to sexual or physical abuse or the death of a
      parent are at higher risk for development of depressive and anxiety disorders
      later in life. Preclinical and clinical studies have shown that repeated early
      life stress leads to alterations in central neurobiological systems, particularly
      in the corticotropin-releasing factor system, leading to increased responsiveness
      to stress. Clearly, exposure to early-life stressors leads to neurobiological
      changes that increase the risk of psychopathology in both children and adults.
      Identification of the neurobiological substrates that are affected by adverse
      experiences in early life should lead to the development of more effective
      treatments for these disorders. The preclinical and clinical studies evaluating
      the consequences of early-life stress are reviewed.

PMID- 14728094
TI  - Risk and resilience in posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a fairly common psychiatric disorder that
      is associated with a lifetime prevalence of approximately 9% in the United
      States. In light of recent war and terrorist activity worldwide, it is likely
      that increased numbers of individuals will be exposed to severe or life
      threatening trauma, and the incidence of PTSD may be even higher than previously
      indicated in epidemiologic studies. PTSD may develop after exposure to a
      traumatic event in which the individual experienced, witnessed, or was confronted
      by either actual or threatened loss of life or serious injury. Patients with PTSD
      often reexperience intrusive recollections of the event in ways that are highly
      distressing and may be described as reliving the memory. Not surprisingly,
      symptoms of avoidance are noted because individuals with PTSD often wish to
      escape recollections (thoughts, feelings, conversations, places) related to the
      trauma. Patients also experience symptoms of hyperarousal associated with
      difficulty concentrating or exaggerated startle response. Notably, individuals
      who develop PTSD represent only a subset of those exposed to trauma. It is of
      interest why certain individuals are at risk for development of PTSD after
      traumatic exposure, whereas others appear to be more resilient to the effects of
      trauma. Studies suggest that previous exposure to trauma and intensity of the
      response to acute trauma may affect the development of PTSD. In addition,
      however, neuroendocrine changes, such as lower cortisol levels, also may
      influence formation and processing of traumatic memories and may be associated
      with the underlying pathology of PTSD.

PMID- 14728095
TI  - Science for the community: assessing mental health after 9/11.
AB  - Reactions to the September 11 attacks across the United States were pervasive,
      and persons throughout the country reported experiences akin to posttraumatic
      stress disorder (PTSD) in the first week following the attacks. In the New York
      area, 2 major surveys conducted 4 to 8 weeks after the attacks found that
      approximately 1 in 10 persons probably met full criteria for PTSD related to
      September 11. Although tobacco, alcohol, and marijuana use did increase, it was
      largely among persons already using these substances. The greatest increase, not
      surprisingly, occurred among persons with PTSD and major depressive disorder.
      Nationwide during the same time period, rates of PTSD related to September 11
      were estimated at 2.7% to 4.3%, a striking finding in that the attacks were
      witnessed primarily on television outside the New York area. In all studies,
      having anxiety symptoms or meeting criteria for PTSD was strongly associated with
      number of hours of television watched on September 11 and in the days afterward.
      A number of explanations for this new finding are possible. These data can inform
      our understanding of trauma-related diagnoses, further the evolving diagnostic
      definitions of the Diagnostic and Statistical Manual of Mental Disorders, and
      contribute to etiologic models of PTSD. Future directions for postdisaster survey
      research are briefly discussed.

PMID- 14728096
TI  - Long-term treatment and prevention of posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a disabling condition almost universally
      associated with psychiatric comorbidity, reduced quality of life, and a chronic,
      often lifelong, course. Although acute treatment with selective serotonin
      reuptake inhibitors (SSRIs) has been shown to be effective, successful strategies
      for preventing PTSD have not been established. In addition, studies of the long
      term treatment of chronic PTSD are just beginning to emerge. This review
      considers available evidence for the secondary prevention of PTSD in the acute
      aftermath of trauma and the long-term treatment of established PTSD. Unanswered
      questions pertaining to duration of treatment, candidates for long-term
      treatment, and potentially harmful treatments will also be considered.

PMID- 14728097
TI  - Posttraumatic stress disorder in primary care: a hidden diagnosis.
AB  - Posttraumatic stress disorder (PTSD) is common worldwide, with prevalence rates
      ranging from 1% to nearly 40%, depending on the population studied. The
      disability and natural course of PTSD in psychiatric patients have been well
      characterized. However, even though the primary care setting has been described
      as the "de facto mental health care system," surprisingly little is known about
      PTSD in primary care. Available data from primary care clinics in the United
      States and Israel suggest that PTSD may be as prevalent in this setting as has
      been reported in large epidemiologic studies. Patients may be unlikely to endorse
      traumatic experiences or may not consider them related to their current
      psychological problems. The prevalence of PTSD in primary care may indeed be
      higher than expected because of underreporting of domestic violence and other
      histories of trauma. Recognition of PTSD in primary care could be greatly
      improved if simple trauma histories were integrated into routine medical
      examinations. Primary care clinicians who maintain a high index of suspicion for
      PTSD in their patients with positive histories of trauma plus symptoms of
      depression or anxiety or other signs of psychological distress, suicidal thoughts
      or actions, alcohol or substance abuse, or excessive health care service
      utilization may increase the recognition rate of this disorder in their
      practices.

PMID- 14728098
TI  - Consensus statement update on posttraumatic stress disorder from the
      international consensus group on depression and anxiety.
AB  - OBJECTIVE: To provide an update to the "Consensus Statement on Posttraumatic
      Stress Disorder From the International Consensus Group on Depression and Anxiety"
      that was published in a supplement to The Journal of Clinical Psychiatry (2000)
      by presenting important developments in the field, the latest recommendations for
      patient care, and suggestions for future research. PARTICIPANTS: The 4 members of
      the International Consensus Group on Depression and Anxiety were James C.
      Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt.
      Other faculty who were invited by the chair were Randall D. Marshall, Charles B.
      Nemeroff, Arieh Y. Shalev, and Rachel Yehuda. EVIDENCE: The consensus statement
      is based on the 7 review articles in this supplement and the related scientific
      literature. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On
      day 1, the group discussed topics to be represented by the 7 review articles in
      this supplement, and the chair identified key issues for further debate. On day
      2, the group discussed these issues to arrive at a consensus view. After the
      group meetings, the consensus statement was drafted by the chair and approved by
      all faculty. CONCLUSION: There have been advancements in the science and
      treatment of posttraumatic stress disorder. Attention to this disorder has
      increased with recent world events; however, continued efforts are needed to
      improve diagnosis, treatment, and prevention of posttraumatic stress disorder.

PMID- 14728099
TI  - Brainstorms: symptoms and circuits, part 2: anxiety disorders.
AB  - ISSUE: Numerous anxiety disorders may have malfunctioning neuronal circuits in
      common, which may account for the overlapping symptoms and frequent comorbidity
      of many anxiety disorders with one another.

PMID- 14728100
TI  - Combined treatment with methylphenidate and citalopram for accelerated response
      in the elderly: an open trial.
AB  - BACKGROUND: Accelerated antidepressant treatment response may be particularly
      beneficial for older patients, yet there are few data to inform clinical
      practice. We evaluated the potential of methylphenidate to accelerate
      antidepressant response to citalopram and the safety and tolerability of the
      combined treatment in patients with geriatric major depressive disorder. METHOD:
      We studied 11 elderly outpatients aged 70 years and older who were diagnosed with
      DSM-IV major depressive disorder in a 10-week, open-label, structured trial (July
      2001-July 2002). Methylphenidate was tapered and discontinued during weeks 9 and
      10. Response was defined as a Hamilton Rating Scale for Depression (HAM-D) score
      of less than 10. The daily dose of citalopram ranged between 20 and 40 mg, and
      the daily dose of methylphenidate ranged between 5 and 20 mg. RESULTS: Nine
      patients completed the study. Six patients met criteria for accelerated response
      (HAM-D score < 10 and Clinical Global Impressions-Improvement scale score of 1 or
      2 by treatment day 14), and 2 more patients responded by week 3. One patient was
      a nonresponder. The mean (SD) citalopram dose for all subjects was 27.5 (10.3) mg
      and the mean (SD) methylphenidate dose was 12.2 (4.9) mg. The observed side
      effects were mild to moderate in severity and included sedation, nausea, anxiety,
      polyuria, dry mouth, and hypersalivation. CONCLUSION: Methylphenidate
      augmentation of citalopram may be a safe and viable strategy for accelerating
      antidepressant response in elderly depressed patients. The results of this open
      label trial need to be confirmed in a placebo-controlled trial.

PMID- 14728101
TI  - Improving adherence to antidepressants: a systematic review of interventions.
AB  - BACKGROUND: Effectiveness of antidepressant medication is reduced by patients'
      nonadherence. Several interventions to improve adherence in patients diagnosed
      with unipolar depression have been tested. OBJECTIVE: To systematically review
      the effectiveness of interventions that aimed to improve adherence to
      antidepressant medication in patients with unipolar depression. METHOD:
      Systematic review of English-language articles of randomized controlled trials
      obtained by a computerized literature search of MEDLINE (1966-January 2002) using
      the terms patient compliance, patient dropout, treatment refusal, patient
      education, adherence, clinical trial, randomized controlled trial, controlled
      trial, depressive disorder, and depression; PSYCINFO (1984-January 2002) using
      the terms random, clinical, control, trial, adherence, compliance, noncompliance,
      dropouts, patient education, depression, major depression, affective disorders,
      and dysthymic disorder; EMBASE (1980-January 2002) using the terms patient
      compliance, patient dropouts, illness behavior, treatment refusal, patient
      education, clinical trial, controlled study, randomized controlled trial, and
      depression; and the Cochrane Controlled Trials Register (no restrictions) using
      the terms random*, complian*, adheren*, pharmacotherapy, regimen*, educat*,
      medicat*, depression, and depressive disorder. RESULTS: Educational interventions
      to enhance adherence failed to demonstrate a clear benefit on adherence and
      depression outcome. However, collaborative care interventions tested in primary
      care demonstrated significant improvements in adherence during the acute and
      continuation phase of treatment and were associated with clinical benefit,
      especially in patients suffering from major depression who were prescribed
      adequate dosages of antidepressant medication. CONCLUSION: We found evidence to
      support the introduction of interventions to enhance adherence with
      antidepressant medication in primary care, not only because of better adherence
      but also because of better treatment results. Because collaborative care
      interventions require additional resources, a better understanding of the mode of
      action of different programs is needed to reduce avoidable costs. The
      effectiveness of educational interventions needs more evidence.

PMID- 14728102
TI  - Tiagabine for posttraumatic stress disorder: a case series of 7 women.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is often a chronic disorder,
      and, though 2 antidepressants are now approved by the U.S. Food and Drug
      Administration for its treatment, it often remains refractory to pharmacotherapy.
      The memory of traumatic events, by repeatedly stimulating the hippocampus and
      amygdala (kindling phenomenon), may alter multiple biological systems, including
      gamma-aminobutyric acid (GABA) pathways, and eventually lead to the disorder.
      Tiagabine, a selective GABA reuptake inhibitor, was evaluated as a treatment for
      PTSD. METHOD: Patients with DSM-IV PTSD who were stable on current medications
      and still symptomatic were eligible for inclusion in this open-label case series.
      Tiagabine was initiated at 2 mg nightly and increased by 2-mg increments every 2
      to 3 days until an optimal response was achieved. The Clinical Global Impressions
      Improvement scale and PTSD Checklist-Civilian Version (PCL-C) were used to
      evaluate changes in PTSD symptoms. RESULTS: Seven consecutive female patients
      were identified as eligible. Tiagabine markedly improved PTSD symptoms within 2
      weeks for 6 of the 7 patients, and 6 patients were rated as "much improved" or
      "very much improved." The mean PCL-C score was significantly reduced at weeks 2
      and 8 (p <.05) as were the 3 PCL-C subscales and 1 of 2 items related to sleep
      disturbance. The mean effective daily dosage was approximately 8 mg (range, 4-12
      mg/day). Treatment with tiagabine was generally well tolerated. CONCLUSIONS:
      These preliminary open-label findings suggest that the selective GABA reuptake
      inhibitor tiagabine may be a promising therapeutic option in the treatment of
      PTSD. Further study into the efficacy and safety of tiagabine for the treatment
      of PTSD is warranted.

PMID- 14728103
TI  - Bipolar disorder, obesity, and pharmacotherapy-associated weight gain.
AB  - BACKGROUND: Bipolar disorder, overweight, and obesity are each national public
      health problems. Overweight and obesity also appear to be related to mood
      disorders, and patients with bipolar disorder, in particular, may be at greater
      risk for overweight and obesity than individuals in the general population. This
      risk may be due to factors associated with the illness itself and/or with
      medications used to treat bipolar disorder. METHOD: We conducted a MEDLINE
      literature search of all English-language articles (1966-2002) using the keywords
      lithium, olanzapine, valproate, valproic acid, divalproex sodium, carbamazepine,
      lamotrigine, obesity, weight, and bipolar disorder. We augmented this search with
      manual review of relevant references. Our focus was on studies examining the
      prevalence of overweight and obesity in bipolar disorder, the risk and magnitude
      of weight gain associated with medications used to treat bipolar disorder, and
      the prevention and treatment of overweight and obesity in patients with bipolar
      disorder. RESULTS: Forty-five studies were reviewed. Patients with bipolar
      disorder appear to be at greater risk than the general population for overweight
      and obesity. Comorbid binge-eating disorder; the number of depressive episodes;
      treatment with medications associated with weight gain, alone or in combination;
      excessive carbohydrate consumption; and low rates of exercise appear to be risk
      factors for weight gain and obesity in patients with bipolar disorder.
      CONCLUSIONS: More research is required to identify the impact of specific risk
      factors for overweight and obesity in patients with bipolar disorder. These data
      could be used to develop better weight gain prevention and treatment programs for
      those with bipolar disorder. Therapeutic options include dietary counseling, use
      of mood stabilizers with lower propensities for weight gain, and combination
      pharmacotherapy with medications that have weight loss properties.

PMID- 14728104
TI  - Olanzapine induces insulin resistance: results from a prospective study.
AB  - BACKGROUND: The aim of this study was to compare glucose metabolism in patients
      with schizophrenia receiving olanzapine with that in control subjects. METHOD: We
      conducted a prospective, controlled, open study comparing body weight, fat mass,
      and indices of insulin resistance/ sensitivity in 10 olanzapine-treated patients
      with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a
      group of 10 mentally and physically healthy volunteers. Weight, fat mass, and
      indices of insulin resistance/sensitivity were assessed over individual 8-week
      observation periods from November 1997 to October 1999. RESULTS: Fasting serum
      glucose and fasting serum insulin increased significantly in the olanzapine
      treated patients (p =.008 for glucose and p =.006 for insulin). The homeostasis
      model assessment (HOMA) index for beta cell function did not change significantly
      in the olanzapine-treated patients, whereas the HOMA index for insulin resistance
      did increase (p =.006). In the control group, these parameters were stable. A
      significant increase in body weight (p =.001) and body fat (p =.004) was seen in
      patients treated with olanzapine, while the control group showed no significant
      changes. CONCLUSION: This study indicates that the disturbances in glucose
      homeostasis during antipsychotic treatment with olanzapine are mainly due to
      insulin resistance. However, beta cell function remains unaltered in olanzapine
      treated patients. We conclude that treatment with some second-generation
      antipsychotic drugs may lead to insulin resistance.

PMID- 14728105
TI  - Randomized placebo-controlled trial of baclofen for cocaine dependence:
      preliminary effects for individuals with chronic patterns of cocaine use.
AB  - BACKGROUND: This screening trial evaluated whether the GABAB agonist baclofen
      demonstrated sufficient clinical efficacy to recommend an adequately powered
      trial of the medication as a pharmacotherapy for cocaine dependence. METHOD:
      Participants with cocaine dependence verified by the Structured Clinical
      Interview for DSM-IV were randomly assigned to baclofen (N = 35; 20 mg t.i.d.) or
      placebo conditions (N = 35; identical in appearance and dosage rate) using a 2
      group, experimental, 16-week double-blind design featuring thrice-weekly
      cognitive-behavioral drug counseling groups. Outcomes were retention, cocaine
      use, cocaine craving, and adverse events. RESULTS: A generalized estimating
      equation (GEE) model showed that participants assigned to receive baclofen
      demonstrated statistically significant reductions in cocaine use over those
      assigned to receive placebo as indicated by urine drug screening results (chi(2)
      = 5.34, df = 1, p =.021). Confirming the GEE model, longitudinal analyses showed
      that participants assigned to receive baclofen demonstrated significant and
      stepwise increases in the probability of providing benzoylecgonine-free urine
      samples throughout the trial as the number of benzoylecgonine-positive samples
      increased during baseline (chi(2) = 10.63, df = 1, p =.001). Participants
      assigned to placebo demonstrated no such association. Univariate analyses of
      aggregates of urine drug screening showed generally favorable outcomes for
      baclofen, but not at statistically significant levels. There was no statistical
      significance observed for retention, cocaine craving, or incidence of reported
      adverse events by treatment condition. CONCLUSIONS: Project findings demonstrated
      initial clinical efficacy of baclofen over placebo in reducing cocaine use when
      delivered concurrent with thrice-weekly drug abuse counseling sessions. The
      effects of baclofen were particularly apparent for those participants with
      chronic levels of cocaine use at baseline and provide support for a full-scale
      efficacy trial for baclofen, especially among this subgroup of patients.

PMID- 14728106
TI  - Treatment of bulimia nervosa with topiramate in a randomized, double-blind,
      placebo-controlled trial, part 2: improvement in psychiatric measures.
AB  - BACKGROUND: We conducted a 10-week, randomized, double-blind, placebo-controlled
      trial to examine the efficacy of topiramate in the treatment of bulimia nervosa.
      Primary efficacy analyses showed that topiramate treatment significantly reduced
      days on which patients binged and/or purged. This article describes further
      analyses investigating topiramate's effect on psychological symptoms associated
      with disordered eating. METHOD: Patients with DSM-IV bulimia nervosa were
      randomly assigned to receive topiramate (N = 35) or placebo (N = 34) for 10
      weeks. Topiramate treatment was started at 25 mg/day and titrated by 25 to 50
      mg/week to a maximum of 400 mg/day. Secondary psychiatric endpoints, including
      the Eating Disorder Inventory (EDI), Eating Attitudes Test (EAT), Hamilton Rating
      Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression (HAM-D), and
      Patient Global Improvement (PGI) were assessed for change from baseline in the
      topiramate versus placebo group. RESULTS: Thirty-one patients receiving
      topiramate and 33 receiving placebo were included in the intent-to-treat
      analysis. Percent change from baseline on the EDI indicated significantly greater
      improvement in the topiramate group compared with the placebo group for subscales
      measuring bulimia/uncontrollable overeating (p =.005), body dissatisfaction (p
      =.007), and drive for thinness (p =.002). The EAT showed significant improvement
      in the topiramate group compared with the placebo group for the bulimia/food
      preoccupation (p =.019) and dieting (p =.031) subscales and the total score (p
      =.022). For the topiramate group, the reduction in mean HAM-A score was
      significantly greater (p =.046) than that in the placebo group, while reduction
      in HAM-D scores was greater in the topiramate group compared with the placebo
      group but did not reach statistical significance (p =.069). Significantly more
      patients treated with topiramate compared with placebo reported improvement on
      the PGI (p =.004). CONCLUSION: Topiramate treatment improves multiple behavioral
      dimensions of bulimia nervosa. Binge and purge behaviors are reduced, and
      treatment is associated with improvements in self-esteem, eating attitudes,
      anxiety, and body image. These results support topiramate as a viable therapeutic
      option for the treatment of bulimia nervosa. Additional, longer-term multicenter
      trials are indicated.

PMID- 14728107
TI  - Increased cholesterol levels during paroxetine administration in healthy men.
AB  - BACKGROUND: Despite the frequent use of selective serotonin reuptake inhibitors
      in patients with coronary heart disease (CHD), their effects on plasma lipid
      levels have not been systematically investigated. Our objective was to assess the
      effects of 8 weeks of paroxetine administration on plasma cholesterol and
      triglyceride levels. METHOD: Blood samples were collected at baseline, after 8
      weeks of paroxetine administration, and post-discontinuation in 18 healthy male
      volunteers. RESULTS: In the 16 of 18 patients whose plasma levels of paroxetine
      indicated an unequivocal compliance to treatment, paroxetine administration
      induced an 11.5% increase in low-density lipoprotein cholesterol (LDL-C), which
      normalized after paroxetine discontinuation. CONCLUSION: The magnitude of the
      paroxetine-induced increase in LDL-C would lead to a minor increase in CHD risk
      in a minority of healthy male volunteers without associated CHD risk factors but
      might increase LDL-C sufficiently to warrant therapeutic intervention in patients
      with established CHD, based on the National Cholesterol Education Program
      guidelines.

PMID- 14728108
TI  - Hostility during admission interview as a short-term predictor of aggression in
      acute psychiatric male inpatients.
AB  - BACKGROUND: A critical step for improving the prediction of on-ward violence is
      the identification of variables that are not only consistently associated with an
      increased risk of aggression but also easily evaluated during the admission
      interview. The goal of this prospective study was to assess the predictive
      utility of hostility during admission interview. METHOD: The sample consisted of
      80 newly admitted male patients with heterogeneous DSM-IV psychiatric diagnoses
      recruited from the psychiatric ward of an urban public hospital. Psychiatric
      symptoms at admission were assessed with the Brief Psychiatric Rating Scale
      (BPRS). Aggressive behavior during the first week of hospitalization was measured
      with the Modified Overt Aggression Scale. Data were collected between January and
      June 1998. RESULTS: In a multiple regression model, BPRS items hostility and
      tension-excitement emerged as significant predictors of verbal aggression,
      whereas thinking disturbance (high) and suspiciousness-uncooperativeness (low)
      emerged as significant predictors of aggression against objects. In contrast,
      when aggression was treated as a binary dependent variable in a logistic model,
      hostility during the admission interview had no utility in predicting on-ward
      aggressive behavior. CONCLUSION: This study confirms the importance of
      distinguishing between different types of aggression to improve the accuracy of
      predictions of violence. The findings suggest that the question whether hostility
      is a useful short-term predictor of aggression in psychiatric inpatients cannot
      be answered conclusively. The predictive utility of hostility was relatively high
      for predicting verbal aggression but was negligible for predicting other types of
      aggressive behavior.

PMID- 14728109
TI  - The economic burden of depression in the United States: how did it change between
      1990 and 2000?
AB  - BACKGROUND: The economic burden of depression was estimated to be 43.7 billion
      dollars in 1990. A subsequent study reported a cost burden of 52.9 billion
      dollars using revised prevalence data and a refined workplace cost estimation
      approach. The objective of the current report is to provide a 10-year update of
      these estimates using the same methodological framework. METHOD: Using a human
      capital approach, we developed prevalence-based estimates of 3 major cost
      categories: (1) direct costs, (2) mortality costs arising from depression-related
      suicides, and (3) costs associated with depression in the workplace. Cost-of
      illness estimates from 1990 were updated to reflect the experience in 2000 using
      current epidemiologic data and publicly available population, wage, and cost
      information. RESULTS: Whereas the treatment rate of depression increased by over
      50%, its economic burden rose by only 7%, going from 77.4 billion dollars in 1990
      (inflation-adjusted dollars) to 83.1 billion dollars in 2000. Of the 2000 total,
      26.1 billion dollars (31%) were direct medical costs, 5.4 billion dollars (7%)
      were suicide-related mortality costs, and 51.5 billion dollars (62%) were
      workplace costs. CONCLUSION: The economic burden of depression remained
      relatively stable between 1990 and 2000, despite a dramatic increase in the
      proportion of depression sufferers who received treatment. Future research will
      incorporate additional costs associated with depression sufferers, including the
      excess costs of their coexisting psychiatric and medical conditions and attention
      to the role of painful conditions as a driver of these costs.

PMID- 14728110
TI  - Anxiety symptoms and quality of life in middle-aged and older outpatients with
      schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: This study examined whether anxiety symptoms make an independent
      contribution to poorer quality of life among middle-aged and older outpatients
      with schizophrenia or schizoaffective disorder. METHOD: We evaluated data from an
      ongoing study of 163 older patients with DSM-III-R or DSM-IV schizophrenia or
      schizoaffective disorder who were enrolled in research at the University of
      California, San Diego, Advanced Center for Interventions and Services Research
      from October 1992 to April 1998. Measures used were the anxiety, somatization,
      obsessive-compulsive, and phobic anxiety subscales of the Brief Symptom
      Inventory. We performed hierarchical multiple regressions with forced entry of
      variables to determine whether anxiety symptoms significantly predicted poorer
      health-related quality of life (measured by 2 scales) after controlling for
      demographic variables, akathisia, cognitive impairment, depressive symptoms, and
      overall psychopathology. RESULTS: Anxiety symptoms were associated with poorer
      outcomes on overall quality of well-being and subscales representing vitality,
      social functioning, and role functioning limitations due to physical problems. In
      most cases, the proportion of variance in quality of life accounted for by
      anxiety symptoms was greater than that accounted for by depressive symptoms.
      CONCLUSIONS: Results suggest that anxiety symptoms have a significant negative
      impact on the quality of life of middle-aged and older patients with
      schizophrenia and schizoaffective disorder.

PMID- 14728111
TI  - Rapid and non-rapid cycling bipolar disorder: a meta-analysis of clinical
      studies.
AB  - BACKGROUND: Rapid cycling, defined as 4 or more mood episodes per year, is a
      course specifier of bipolar disorder associated with relative treatment
      resistance. Several risk factors have been suggested to be associated with rapid
      cycling. The purpose of this meta-analysis was to compare clinical studies for
      the evidence of discriminating factors between rapid and non-rapid cycling. DATA
      SOURCES AND SELECTION: We searched MEDLINE and reference lists of articles and
      book chapters and selected all of the clinical studies published from 1974 to
      2002 comparing subjects with rapid and non-rapid cycling bipolar disorder.
      Prevalence rates and mean random effect sizes for 18 potential risk factors that
      were reported by at least 3 studies were calculated. In addition, we
      differentiated between current and lifetime diagnoses of rapid cycling. DATA
      SYNTHESIS: Twenty studies were identified. Rapid cycling was present in 16.3% of
      2054 bipolar patients in 8 studies that included patients who were consecutively
      admitted to an inpatient or outpatient facility, without a priori selection of
      rapid cyclers and without matching the numbers of rapid cyclers to non-rapid
      cycling controls. Female gender and bipolar II subtype both had a small, but
      statistically significant, effect (p <.000 for female gender, p <.001 for bipolar
      II subtype). The further absence of recurrences with lithium prophylaxis was
      reported in 34% of rapid cyclers compared with 47% of non-rapid cyclers, a nearly
      significant difference, and a partial response was present in 59% and 65% of
      patients, respectively. The effect of hypothyroidism was significant (p <.01) in
      studies using current, but not lifetime, definitions of rapid cycling. In 46% of
      cases, a rapid cycling course was preceded by treatment with antidepressants, but
      systematic data on their causal role are lacking. CONCLUSION: Rapid cycling is
      slightly more prevalent in women and in patients with bipolar II subtype. In
      contrast to common opinion, lithium prophylaxis has at least partial efficacy in
      a considerable number of rapid cyclers, especially when antidepressants are
      avoided. Hypothyroidism may be associated with mood destabilization in vulnerable
      patients.

PMID- 14728112
TI  - Possible basal ganglia pathology in children with complex symptoms.
AB  - BACKGROUND: Clinical observation of children presenting with a myriad of motor,
      behavioral, emotional, and sensorial symptoms who do not respond to treatment led
      to the hypothesis that these children may constitute a unique population, perhaps
      even a new clinical entity. The literature on child and adolescent
      psychopathology does not specifically address the phenomenological, diagnostic,
      and etiological factors that make these children unique. For this reason, a
      preliminary study was conducted to identify additional symptoms and features that
      make these children different. METHOD: Data were collected in 2001 on 7 children
      with complex symptomatology using the Behavior Assessment System for Children,
      the Anxiety Disorders Interview Schedule for DSM-IV, and a neurological illnesses
      and symptoms questionnaire designed by the authors. RESULTS: On average, these
      children met full DSM-IV criteria for 1 to 5 diagnoses. The most prevalent
      diagnoses were attention-deficit/hyperactivity disorder, obsessive-compulsive
      disorder, oppositional defiant disorder, and pervasive developmental disorder.
      These children also exhibited a high incidence of sensory hyperarousal,
      aggressiveness, hypersexuality, and neuroethological behaviors. Almost all of the
      children also had indications of a history of bacterial or viral infection.
      CONCLUSION: The specific symptoms identified and the biological factors found in
      many of the children seem to suggest basal ganglia involvement.

PMID- 14728113
TI  - A critical review of selective serotonin reuptake inhibitor-associated bleeding:
      balancing the risk of treating hepatitis C-infected patients.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are increasingly
      being used to treat interferon-associated side effects in patients receiving
      hepatitis C virus (HCV) therapy. Because there is an increased risk of bleeding
      in HCV-infected patients who have developed cirrhosis and either portal
      hypertension or hepatic failure or both, we critically reviewed the literature on
      SSRI-associated bleeding. DATA SOURCES AND STUDY SELECTION: We performed a
      MEDLINE search of literature from 1966 to the present using hemorrhage, SSRI, and
      antidepressants as search terms and followed up on relevant citations. We
      reviewed 6 retrospective studies, 5 of which were case-control studies, and 18
      case reports of bleeding in 37 people. Our review is supplemented with a case
      report of a possible connection between SSRI treatment and a fatal
      gastrointestinal bleed in an HCV-infected man. DATA SYNTHESIS: Bleeding events in
      12/18 reports (67%) describing 19/24 people (79%) were closely associated with
      the use of SSRIs. CONCLUSION: Combining aspirin or nonsteroidal anti-inflammatory
      drugs with SSRIs for the treatment of interferon-associated neuropsychiatric side
      effects increases the risks of hemorrhage in patients with HCV who have developed
      cirrhosis and either portal hypertension or hepatic failure or both. We recommend
      that clinicians exercise caution when prescribing medications that can promote
      spontaneous bleeding to patients with multiple risk factors for internal
      hemorrhage.

PMID- 14728114
TI  - Comparison of managed care charges among patients treated with selective
      serotonin reuptake inhibitors for premenstrual dysphoric disorder.
AB  - OBJECTIVE: To determine the impact on managed care charges of selecting
      citalopram, fluoxetine, paroxetine, or sertraline as first-line pharmacotherapy
      for newly diagnosed premenstrual dysphoric disorder (PMDD). METHOD: This
      retrospective study analyzed administrative claims data from 14 managed care
      plans in the United States. The study population was identified from an
      integrated outcomes database for the period Jan. 1, 1998, to Dec. 31, 1999.
      Patients aged 18 years or older, newly diagnosed with PMDD, and initiating
      therapy with a selective serotonin reuptake inhibitor (SSRI) within 30 days of
      the diagnosis were eligible for analysis. To date, there is no specific ICD-9
      diagnosis code for PMDD; thus, patients were required to have an ICD-9 diagnosis
      of premenstrual tension syndrome (ICD-9 625.4). Patients with documented previous
      psychiatric disorders/treatment were excluded. All inpatient, outpatient, and
      pharmacy claims incurred by each patient during the study period were included in
      the analysis. PMDD-related treatment charges for the 6-month period following
      treatment initiation were compared using multivariate regression. RESULTS: A
      total of 1413 patients met the study criteria. Fluoxetine and sertraline were the
      most common agents selected as first-line therapy. After differences in age,
      managed care plan, pretreatment resource utilization, physician specialty, index
      prescription year, treatment charges, presence of mental health and nonmental
      health comorbid conditions, and changes in medication were controlled for,
      patients taking paroxetine and citalopram had significantly higher PMDD-related
      treatment charges than sertraline patients (paroxetine, p =.0430; citalopram, p
      =.0226). Fluoxetine patients also had higher treatment charges than sertraline
      patients, though statistical significance was not reached. CONCLUSIONS:
      Sertraline, as first-line therapy for PMDD, was associated with lower PMDD
      related treatment charges compared with other SSRIs during the first 6 months
      after treatment initiation.

PMID- 14728115
TI  - Agitation and inpatient suicide.

PMID- 14728117
TI  - Treatment of anxiety in suicidal patients.

PMID- 14728119
TI  - Effectiveness of close watch precautions in suicidal patients.

PMID- 14728121
TI  - Two cases of quetiapine augmentation for donepezil-refractory visual
      hallucinations in dementia with Lewy bodies.

PMID- 14728122
TI  - TLC-Asthma: an integrated information system for patient-centered monitoring,
      case management, and point-of-care decision support.
AB  - A great deal of successful work has been done in the area of EMR development,
      implementation, and evaluation. Less work has been done in the area of automated
      systems for patients. Efforts to link data at multiple levels - the patient, the
      case manager, and the clinician have been rudimentary to-date. In this paper we
      present a model information system that integrates patient health information
      across multiple domains to support the monitoring and care of children with
      persistent asthma. The system has been developed for use in a multi-specialty
      group practice and includes three primary components: 1) a patient-centered
      telephone-linked communication system; 2) a web-based alert reporting and nurse
      case-management system; and 3) EMR-based provider communication to support
      clinical decision making at the point-of-care. The system offers a model for a
      new level of connectivity for health information that supports customized
      monitoring, IT-enabled nurse case-managers, and the delivery of longitudinal data
      to clinicians to support the care of children with persistent asthma. Systems
      like the one described are well-suited, perhaps essential, technologies for the
      care of children and adults with chronic conditions such as asthma.

PMID- 14728123
TI  - Assessment of a computer-aided instructional program for the pediatric emergency
      department.
AB  - Computer aided instruction (CAI) software is becoming commonplace in medical
      education. Our experience with CAI programs in our pediatric ED raised concerns
      about the time commitment some of these programs require. We developed a just-in
      time learning program, the Virtual Preceptor (VP) and evaluated this program for
      use in a busy clinical environment. Forty-three of 47 pediatric residents used
      the VP at least once. Interns used the program 2 (1/2) times more often than
      upper level residents. Of 321 topics available in 18 subject categories, 153
      (48%) were selected at least once. Content was rated as appropriate by 72% of
      users. 95% of residents would use the program again. Although no resident felt
      the program itself took too long to use, 51% said they were too busy to use the
      VP. Time of use and level of training may be important factors in CAI use in the
      pediatric ED environment.

PMID- 14728124
TI  - Developing quality indicators and auditing protocols from formal guideline
      models: knowledge representation and transformations.
AB  - Automated quality assessment of clinician actions and patient outcomes is a
      central problem in guideline- or standards-based medical care. In this paper we
      describe a model representation and algorithm for deriving structured quality
      indicators and auditing protocols from formalized specifications of guidelines
      used in decision support systems. We apply the model and algorithm to the
      assessment of physician concordance with a guideline knowledge model for
      hypertension used in a decision-support system. The properties of our solution
      include the ability to derive automatically context-specific and case-mix
      adjusted quality indicators that can model global or local levels of detail about
      the guideline parameterized by defining the reliability of each indicator or
      element of the guideline.

PMID- 14728125
TI  - Leveraging of open EMR architecture for clinical trial accrual.
AB  - Accrual to clinical trials is a major bottleneck in scientific progress in
      clinical medicine. Many methods for identifying potential subjects and improving
      accrual have been pursued; few have succeeded, and none have proven generally
      reproducible or scalable. We leveraged the open architecture of the core clinical
      data repository of our electronic medical record system to prototype a solution
      for this problem in a manner consistent with contemporary regulations and
      research ethics. We piloted the solution with a local investigator-initiated
      trial for which candidate identification was expected to be difficult. Key
      results in the eleven months of experience to date include automated screening of
      7,296,708 lab results from 69,288 patients, detection of 1,768 screening tests of
      interest, identification of 70 potential candidates who met all further automated
      criteria, and accrual of three candidates to the trial. Hypotheses for this
      disappointing impact on accrual, and directions for future research, are
      discussed.

PMID- 14728126
TI  - HITON: a novel Markov Blanket algorithm for optimal variable selection.
AB  - We introduce a novel, sound, sample-efficient, and highly-scalable algorithm for
      variable selection for classification, regression and prediction called HITON.
      The algorithm works by inducing the Markov Blanket of the variable to be
      classified or predicted. A wide variety of biomedical tasks with different
      characteristics were used for an empirical evaluation. Namely, (i) bioactivity
      prediction for drug discovery, (ii) clinical diagnosis of arrhythmias, (iii)
      bibliographic text categorization, (iv) lung cancer diagnosis from gene
      expression array data, and (v) proteomics-based prostate cancer detection. State
      of-the-art algorithms for each domain were selected for baseline comparison.
      RESULTS: (1) HITON reduces the number of variables in the prediction models by
      three orders of magnitude relative to the original variable set while improving
      or maintaining accuracy. (2) HITON outperforms the baseline algorithms by
      selecting more than two orders-of-magnitude smaller variable sets than the
      baselines, in the selected tasks and datasets.

PMID- 14728127
TI  - The classification of clinicians' information needs while using a clinical
      information system.
AB  - INTRODUCTION: Information needs are prevalent in clinical practice. They
      represent a potential source of medical errors. This study seeks to empirically
      determine the information needs of clinicians while using a clinical information
      system (CIS), and characterize those needs. In addition this paper will provide
      the framework necessary for the development of the solutions to these information
      needs. METHODS: Clinicians were observed while using a CIS. They were recorded on
      audiotape and the computer screen recorded on videotape. The types of question
      during these interactions were recorded. A classification of the questions
      provided the conceptual and architectural basis for the development of context
      sensitive links to information resources, called infobuttons. RESULTS: There were
      154 information needs. The questions were grouped into seven categories. Within
      these categories we were able to identify eleven specific repeated question
      patterns, accounting for 72 or 47% of users' questions. DISCUSSION: These
      findings are applicable to a number of settings and can be generalized to other
      institutions. The proposed infobuttons based on six categories, will be
      navigational ('how-to.' links), cross-reference ('what is the em leader ' links),
      domain knowledge buttons in the areas of laboratory, pharmacy, diagnosis, and
      definitions/general information. Using these groups we were able to identity
      eleven patterns of questions.

PMID- 14728128
TI  - Text categorization models for retrieval of high quality articles in internal
      medicine.
AB  - The discipline of Evidence Based Medicine (EBM) studies formal and quasi-formal
      methods for identifying high quality medical information and abstracting it in
      useful forms so that patients receive the best customized care possible [1].
      Current computer-based methods for finding high quality information in PubMed and
      similar bibliographic resources utilize search tools that employ preconstructed
      Boolean queries. These clinical queries are derived from a combined application
      of (a) user interviews, (b) ad-hoc manual document quality review, and (c) search
      over a constrained space of disjunctive Boolean queries. The present research
      explores the use of powerful text categorization (machine learning) methods to
      identify content-specific and high-quality PubMed articles. Our results show that
      models built with the proposed approach outperform the Boolean based PubMed
      clinical query filters in discriminatory power.

PMID- 14728129
TI  - Principles for a successful computerized physician order entry implementation.
AB  - To identify success factors for implementing computerized physician order entry
      (CPOE), our research team took both a top-down and bottom-up approach and
      reconciled the results to develop twelve overarching principles to guide
      implementation. A consensus panel of experts produced ten Considerations with
      nearly 150 sub-considerations, and a three year project using qualitative methods
      at multiple successful sites for a grounded theory approach yielded ten general
      themes with 24 sub-themes. After reconciliation using a meta-matrix approach,
      twelve Principles, which cluster into groups forming the mnemonic CPOE emerged.
      Computer technology principles include: temporal concerns; technology and meeting
      information needs; multidimensional integration; and costs. Personal principles
      are: value to users and tradeoffs; essential people; and training and support.
      Organizational principles include: foundational underpinnings; collaborative
      project management; terms, concepts and connotations; and improvement through
      evaluation and learning. Finally, Environmental issues include the motivation and
      context for implementing such systems.

PMID- 14728130
TI  - Informatics competencies pre-and post-implementation of a Palm-based student
      clinical log and informatics for evidence-based practice curriculum.
AB  - The purpose of this paper is to describe the implementation and evaluation of a
      two-part approach to achieving informatics competencies: 1) Palm-based student
      clinical log for documentation of patient encounters; and 2) informatics for
      evidence-based practice curriculum. Using a repeated-measures, non-equivalent
      control group design, self-reported informatics competencies were rated using a
      survey instrument based upon published informatics competencies for beginning
      nurses. For the class of 2002, scores increased significantly in all competencies
      from admission to graduation. Using a minimum score of 3 on a scale of 1=not
      competent and 5=expert to indicate competence, the only area in which it was not
      achieved was Computer Skills: Education. For 2001 graduates, Computer Skills:
      Decision Support was also below 3. There were no significant differences in
      competency scores between 2001 and 2002 graduates. Computer Skills: Decision
      Support neared significance. Subsequently, the approaches were refined for
      implementation in the class of 2003.

PMID- 14728131
TI  - NOSTOS: a paper-based ubiquitous computing healthcare environment to support data
      capture and collaboration.
AB  - In this paper, we present a new approach to clinical workplace computerization
      that departs from the window-based user interface paradigm. NOSTOS is an
      experimental computer-augmented work environment designed to support data capture
      and teamwork in an emergency room. NOSTOS combines multiple technologies, such as
      digital pens, walk-up displays, headsets, a smart desk, and sensors to enhance an
      existing paper-based practice with computer power. The physical interfaces allow
      clinicians to retain mobile paper-based collaborative routines and still benefit
      from computer technology. The requirements for the system were elicited from
      situated workplace studies. We discuss the advantages and disadvantages of
      augmenting a paper-based clinical work environment.

PMID- 14728132
TI  - The UMLS knowledge source server: an object model for delivering UMLS data.
AB  - The Unified Medical Language System (UMLS), a project of the National Library of
      Medicine (NLM), regularly distributes a set of knowledge sources to the research
      community. These data are made available over the Internet through the UMLS
      Knowledge Source Server (UMLSKS). The new version of the UMLSKS is a complete
      redesign of the original system using Java and the Extensible Markup Language
      (XML) technologies to implement a fast, reliable, flexible, and extensible UMLS
      data retrieval system that includes an Application Programmer's Interface (API)
      and an Object Model of each of the Knowledge Sources: the UMLS Metathesaurus, the
      Semantic Network, and the SPECIALIST Lexicon. In this paper we present the design
      of the new system, outline each of the system design goals, the UMLS Object
      Model, and statistics showing the usage of the new UMLSKS and associated data. We
      conclude with implications for future work.

PMID- 14728133
TI  - A web application to support telemedicine services in Brazil.
AB  - This paper describes a system that has been developed to support Telemedicine
      activities in Brazil, a country that has serious problems in the delivery of
      health services. The system is a part of the broader Tele-health Project that has
      been developed to make health services more accessible to the low-income
      population in the northeast region. The HealthNet system is based upon a pilot
      area that uses fetal and pediatric cardiology. This article describes both the
      system's conceptual model, including the tele-diagnosis and second medical
      opinion services, as well as its architecture and development stages. The system
      model describes both collaborating tools used asynchronously, such as discussion
      forums, and synchronous tools, such as videoconference services. Web and free-of
      charge tools are utilized for implementation, such as Java and MySQL database.
      Furthermore, an interface with Electronic Patient Record (EPR) systems using
      Extended Markup Language (XML) technology is also proposed. Finally,
      considerations concerning the development and implementation process are
      presented.

PMID- 14728134
TI  - Distribution of a primary care office information system.
AB  - Primary Care Office InSite (PCOI) is a Web-based intranet application that
      provides ready access to a collection of information useful in primary care. The
      PCOI Web site was developed by, and is widely used within, the Massachusetts
      General Hospital (MGH) and its affiliated community practices. Over 1600 users
      logged 60,000 separate sessions in the past year. The site contains clinical
      practice guidelines, patient educational material, drug prescription and cost
      information and referral information, all designed for use during routine patient
      care activity. This paper discusses the problems encountered and the lessons
      learned during an ongoing experiment to disseminate PCOI via the Internet to four
      distant and very different ambulatory care sites. None of these sites (a rural
      community hospital, a city-wide health care network, an inner-city general
      hospital, and an Indian Health Service hospital have the resources to develop
      such an application internally.

PMID- 14728135
TI  - Linking guidelines to Electronic Health Record design for improved chronic
      disease management.
AB  - The promise of electronic decision support to promote evidence based practice
      remains elusive in the context of chronic disease management. We examine the
      problem of achieving a close relationship of Electronic Health Record (EHR)
      content to other components of a clinical information system (guidelines,
      decision support and workflow), particularly linking the decisions made by
      providers back to the guidelines. We use the openEHR architecture, which allows
      extension of a core Reference Model via Archetypes to refine the detailed
      information recording options for specific classes of encounter. We illustrate
      the use of openEHR for tracking the relationship of a series of clinical
      encounters to a guideline via a case study of guideline-compliant treatment of
      hypertension in diabetes. This case study shows the contribution guideline
      content can have on problem-specific EHR structure and demonstrates the potential
      for a constructive interaction of electronic decision support and the EHR.

PMID- 14728136
TI  - Logic-based remodeling of the Digital Anatomist Foundational Model.
AB  - This paper describes a development cycle for the engineering of large knowledge
      bases: A graphical tool is used for editing and the content is transformed into a
      logic-based representation language. This representation is used to check the
      consistency of the knowledge base as well as to facilitate the reviewing process.
      Showing the usefulness of this approach, aspects of the Digital Anatomist
      Foundational Model will be transformed into a Description Logics representation.
      We introduce a special modeling technique to account for the representation of
      the complex part/whole relationships in the biomedical domain.

PMID- 14728137
TI  - Clinician performance and prominence of diagnoses displayed by a clinical
      diagnostic decision support system.
AB  - Clinical decision support systems (CDSS) can impact both diagnostic and
      therapeutic decision-making, but physicians sometimes fail to heed the
      appropriate CDSS advice, or become influenced in a negative way by the CDSS. This
      study examined the relationships among clinicians' prior diagnostic accuracy, the
      performance of a diagnostic CDSS, and how the CDSS influenced the accuracy of the
      clinician's subsequent diagnoses. Results showed that (1) clinicians who already
      were considering the correct diagnosis prior to using the CDSS were more likely
      to get the CDSS to produce the correct diagnosis in a prominent position than
      those not considering it initially; (2) physicians are strongly anchored by their
      initial diagnoses prior to using the CDSS; and (3) changes in the clinicians'
      diagnoses after using the CDSS are related to presence or absence of the correct
      diagnosis in the top 10 diagnoses displayed by the CDSS.

PMID- 14728138
TI  - The distribution of online healthcare information: a case study on melanoma.
AB  - To understand the difficulties users face when retrieving comprehensive
      healthcare information, this paper analyzes how facts related to a widely
      available healthcare topic are distributed across high-quality webpages. An inter
      rater experiment with two skin-cancer physicians helped identify 14 facts
      necessary for a comprehensive understanding of melanoma risk and prevention. A
      second inter-rater experiment analyzed how those facts were distributed across
      189 relevant webpages from high-quality sites. The analysis revealed that the
      distribution of facts is highly skewed, where few pages have many facts, many
      pages have a few facts, and no single page or site provides all the facts. A more
      detailed analysis suggests that the distribution is being caused by a trade-off
      between depth and breadth, leading to the existence of general, specialized, and
      sparse pages. Furthermore, the analyses reveal patterns and complexities in the
      relationships between facts, pages, and websites. These distribution results
      pinpoint the difficulties faced by searchers, and provide insights for the design
      of future systems that guide users in retrieving comprehensive healthcare
      information.

PMID- 14728139
TI  - Using adaptive turnaround documents to electronically acquire structured data in
      clinical settings.
AB  - We developed adaptive turnaround documents (ATDs) to address longstanding
      challenges inherent in acquiring structured data at the point of care. These
      computer-generated paper forms both request and receive patient tailored
      information specifically for electronic storage. In our pilot, we evaluated the
      usability, accuracy, and user acceptance of an ATD designed to enrich a pediatric
      preventative care decision support system. The system had an overall digit
      recognition rate of 98.6% (95% CI: 98.3 to 98.9) and a marksense accuracy of
      99.2% (95% CI: 99.1 to 99.3). More importantly, the system reliably extracted all
      data from 56.6% (95% CI: 53.3 to 59.9) of our pilot forms without the need for a
      verification step. These results translate to a minimal workflow burden to end
      users. This suggests that ATDs can serve as an inexpensive, workflow-sensitive
      means of structured data acquisition in the clinical setting.

PMID- 14728140
TI  - Using contextual design to identify potential innovations for problem based
      learning.
AB  - We report on the use of Contextual Design (CD) to develop models of the
      information management, resource integration, and collaborative processes of
      medical students in problem-based learning groups. CD is a modified ethnographic
      technique designed to provide a detailed understanding of the user's needs.
      Although the technique has been used in non-healthcare related fields, there is
      limited published data on the application of CD within healthcare settings. In
      this pilot study, we evaluated the feasibility of the CD methodology for this
      domain, developed an initial set of CD models, and formulated a series of design
      ideas based on the data. The study helps to clarify the effectiveness and
      feasibility of CD as well as the limitations for using this method in health
      related domains.

PMID- 14728141
TI  - Model-based design and implementation of secure, interoperable EHR systems.
AB  - For designing and implementing secure, interoperable, portable, and future-proof
      EHR systems, a comprehensive and standardized methodology supported by
      appropriate tools has to be established and applied. Based on the component
      paradigm, the ISO Reference Model - Open Distributed Processing has been used to
      describe the different views on information systems deploying the appropriate
      vocabulary for each single model view. The concepts considered rank from legal,
      organizational, and functional up to technical aspects of systems. The
      harmonization of vocabularies can be performed by meta-languages. The approach
      has been demonstrated for the model-based design, implementation and maintenance
      of a clinical study distributed over the Internet.

PMID- 14728142
TI  - Strength in numbers: exploring redundancy in hierarchical relations across
      biomedical terminologies.
AB  - OBJECTIVES: To investigate three aspects of the redundancy of hierarchical
      relations across biomedical terminologies: 1) What proportion of the relations is
      redundant?, 2) Which terminologies tend to overlap with other terminologies?, and
      3) Is there a link between redundancy and semantic consistency?. METHODS:
      Hierarchical relations are counted in the various families of terminologies
      integrated into the UMLS and an index of redundancy is computed for each
      relation. Similarity among sources is computed using the classical cosine method.
      Semantic consistency is evaluated by reference to the UMLS Semantic Network.
      RESULTS: Overall, 29% of the 1,128,261 relations examined exhibit redundancy.
      Most similar sources include consecutive versions of terminologies. The link
      between redundancy and semantic consistency is weak. DISCUSSION: Applications of
      these findings are discussed, including selecting sources, selecting useful
      relations, and auditing the categorization of UMLS concepts.

PMID- 14728143
TI  - Expert consensus for discharge referral decisions using online delphi.
AB  - This paper describes the results of using a modified Delphi approach designed to
      achieve consensus from eight discharge planning experts regarding the decision to
      refer hospitalized older adults for post-discharge follow-up. Experts reviewed
      150 cases using an online website designed to facilitate their interaction and
      efforts to reach agreement on the need for a referral for post-discharge care and
      the appropriate site for such care. In contrast to an average of eight weeks to
      complete just 50 cases using the traditional mail method, the first online Delphi
      round for 150 cases were completed in six weeks. Data provided by experts suggest
      that online Delphi is a time efficient and acceptable methodology for reaching
      group consensus. Other benefits include instant access to Delphi decision
      results, live knowledge of the time requirements and progress of each expert, and
      cost savings in postage, paper, copying, and storage of paper documents. This
      online Delphi methodology is highly recommended.

PMID- 14728144
TI  - Coverage of patient safety terms in the UMLS metathesaurus.
AB  - The integration and large-scale analyses of medical error databases would be
      greatly facilitated by the use of a standard terminology. We investigated the
      availability in the UMLS metathesaurus of concepts that are required for coding
      patient safety data. Terms from three proprietary patient safety terminologies
      were mapped to the concepts in UMLS by an automated mapping program developed by
      us. From these candidate mappings, the concept that matched its corresponding
      term was selected manually. The reliability of the mapping procedure was verified
      by manually searching for terms in the UMLS Knowledge Source Server. Matching
      concepts in UMLS were identified for less than 27% of the terms in the study
      dataset. The matching rates of terms that describe the type of error and the
      causes of errors were even lower. The lack of such terms in the existing standard
      terminologies underscores the need for development of a standard patient safety
      terminology.

PMID- 14728145
TI  - Coverage of oncology drug indication concepts and compositional semantics by
      SNOMED-CT.
AB  - OBJECTIVE: To evaluate SNOMED-CT 's ability to represent simple and compositional
      concepts in FDA approved oncology drug indications. METHODS: Oncology drug
      indications were decomposed into single and compositional concepts. SNOMED-CT's
      coverage of single concepts and the semantics needed to create compositional
      concepts were evaluated using automated and manual techniques. RESULTS: SNOMED-CT
      covered 86.3% of single concepts present in oncology drug indications; 11.3% of
      indications were covered completely. Coverage was best for concepts describing
      diseases, anatomy, and patient characteristics. Medications accounted for 50.5%
      of missing concepts. Excluding drug names, 45.2% of indications were completely
      represented. SNOMED-CT's semantics completely represented 60.1% of compositional
      expressions. CONCLUSIONS: SNOMED-CT's overall coverage of the concepts in
      oncology drug indications was good. Improvements or alternatives are needed for
      medications and semantics.

PMID- 14728146
TI  - An analytic framework fo space-time aberrancy detection in public health
      surveillance data.
AB  - Public health surveillance is changing in response to concerns about
      bioterrorism, which have increased the pressure for early detection of epidemics.
      Rapid detection necessitates following multiple non-specific indicators and
      accounting for spatial structure. No single analytic method can meet all of these
      requirements for all data sources and all surveillance goals. Analytic methods
      must be selected and configured to meet a surveillance goal, but there are no
      uniform criteria to guide the selection and configuration process. In this paper,
      we describe work towards the development of an analytic framework for space-time
      aberrancy detection in public health surveillance data. The framework decomposes
      surveillance analysis into sub-tasks and identifies knowledge that can facilitate
      selection of methods to accomplish sub-tasks.

PMID- 14728147
TI  - Putting data integration into practice: using biomedical terminologies to add
      structure to existing data sources.
AB  - A major purpose of biomedical terminologies is to provide uniform concept
      representation, allowing for improved methods of analysis of biomedical
      information. While this goal is being realized in bioinformatics, with the
      emergence of the Gene Ontology as a standard, there is still no real standard for
      the representation of clinical concepts. As discoveries in biology and clinical
      medicine move from parallel to intersecting paths, standardized representation
      will become more important. A large portion of significant data, however, is
      mainly represented as free text, upon which conducting computer-based inferencing
      is nearly impossible. In order to test our hypothesis that existing biomedical
      terminologies, specifically the UMLS Metathesaurus and SNOMED CT, could be used
      as templates to implement semantic and logical relationships over free text data
      that is important both clinically and biologically, we chose to analyze OMIM
      (Online Mendelian Inheritance in Man). After finding OMIM entries' conceptual
      equivalents in each respective terminology, we extracted the semantic
      relationships that were present and evaluated a subset of them for semantic,
      logical, and biological legitimacy. Our study reveals the possibility of putting
      the knowledge present in biomedical terminologies to its intended use, with
      potentially clinically significant consequences.

PMID- 14728148
TI  - Pediatricians and personal digital assistants: what type are they using?
AB  - Increasing attention is being focused on the potential benefits of personal
      digital assistants (PDA) in medical practice. Although some work has been done to
      investigate their use, it is still unclear what types of PDAs are being used by
      pediatricians, and if they are using different types in different ways. Our goals
      were to determine: (1) which kinds of PDAs were being used by pediatricians; (2)
      if the personal or professional characteristics of pediatricians differ by type
      of PDA they are using; (3) if the types of applications they employ differ by the
      type of PDAs they are using. We randomly selected 2130 pediatricians from the AMA
      masterfile of United States licensed physicians and surveyed them. Of those
      respondents that reported using a PDA, 89.7% use a Palm OS based system, 8.9% use
      a Pocket PC based system, and 1.4% used neither. Residents were significantly
      more likely to use a Palm OS based PDA than non residents (OR 6.32, 95%CI 1.41
      27.53). There were significant associations between the PDA platform being used
      and types of applications being run on them. More than one third of pediatricians
      are using PDAs in clinical practice. Palm OS based systems are much more
      prevalent in clinical practice, and the choice of newer pediatricians.

PMID- 14728149
TI  - Evaluating the C-section rate of different physician practices: using machine
      learning to model standard practice.
AB  - The C-section rate of a population of 22,175 expectant mothers is 16.8%; yet the
      17 physician groups that serve this population have vastly different group C
      section rates, ranging from 13% to 23%. Our goal is to determine retrospectively
      if the variations in the observed rates can be attributed to variations in the
      intrinsic risk of the patient sub-populations (i.e. some groups contain more
      "high-risk C-section" patients), or differences in physician practice (i.e. some
      groups do more C-sections). We apply machine learning to this problem by training
      models to predict standard practice from retrospective data. We then use the
      models of standard practice to evaluate the C-section rate of each physician
      practice. Our results indicate that although there is variation in intrinsic risk
      among the groups, there also is much variation in physician practice.

PMID- 14728150
TI  - Development and comparison of user acceptance of advanced comprehensive triage
      PDA support system with a traditional terminal alternative system.
AB  - An advanced PDA support system for the triage was designed to evaluate users
      inverted exclamation mark | acceptance of this system compared with a traditional
      terminal system. Davis inverted exclamation mark | Technology Acceptance Model
      was used to evaluate users inverted exclamation mark | acceptance. All 72 ER
      nurses in a 2700-bed medical center were invited for the study. The results
      showed that the PDA system was easier to operate than the terminal one, but had
      worse interface. The subjects showed significantly greater willingness to accept
      the terminal system instead of the PDA system. The comparative acceptance of PDA,
      compared with that of the old system, might still be marginally too low if its
      interface couldn inverted exclamation mark |t be improved or no other unique
      practical benefits could be verified.

PMID- 14728151
TI  - Automated discovery of patient-specific clinician information needs using
      clinical information system log files.
AB  - Knowledge about users and their information needs can contribute to better user
      interface design and organization of information in clinical information systems.
      This can lead to quicker access to desired information, which may facilitate the
      decision-making process. Qualitative methods such as interviews, observations and
      surveys have been commonly used to gain an understanding of clinician information
      needs. We introduce clinical information system (CIS) log analysis as a method
      for identifying patient-specific information needs and CIS log mining as an
      automated technique for discovering such needs in CIS log files. We have applied
      this method to WebCIS (Web-based Clinical Information System) log files to
      discover patterns of usage. The results can be used to guide design and
      development of relevant clinical information systems. This paper discusses the
      motivation behind the development of this method, describes CIS log analysis and
      mining, presents preliminary results and summarizes how the results can be
      applied.

PMID- 14728152
TI  - The Effects of CPOE on ICU workflow: an observational study.
AB  - Computerized physician order entry (CPOE) has had demonstrated benefits in error
      reduction and guideline adherence, but its implementation has often been
      complicated by disruptions in established workflow processes. We conducted an
      observational study of the healthcare team in an intensive care unit after the
      implementation of mandatory CPOE. We found that policies designed to increase
      flexibility and safety led to an increased coordination load on the healthcare
      team, and created opportunities for new sources of error. We attribute this in
      part to implicit assumptions in the CPOE system design that execution of
      physician orders is a linear work process. Observational workflow studies are an
      important tool to understand how to redesign CPOE systems so as to avoid harm and
      achieve the full potential of benefit for improved patient safety.

PMID- 14728153
TI  - Automatic section segmentation of medical reports.
AB  - Automated segmentation of medical reports can significantly enhance the
      productivity of the healthcare departments. While many algorithms have been
      developed for document summarization, passage retrieval, and story segmentation
      of news feeds, much less effort has been devoted to parsing of medical documents.
      We present an algorithm specifically developed for medical applications. The
      algorithm consists of two components. First, a rule-based algorithm is used to
      detect the sections that contain labels. It utilizes a knowledge base of commonly
      employed heading labels and linguistic cues seen within training examples. The
      second part of the algorithm handles the detection of unlabeled sections. It uses
      a combination of lexical pattern recognition and a classifier based on an
      expectation model for a particular class of medical reports. The proposed method
      was evaluated on three test corpora containing a total of 129,303 report
      sections. The detection rates for labeled and unlabeled sections for individual
      corpus ranged from 97.4% to 99.4% and from 96.5% to 99.0%, respectively. The rule
      based approach is particularly effective for medical reports due to inherently
      structured nature of these documents.

PMID- 14728154
TI  - Stratification of adverse outcomes by preoperative risk factors in coronary
      artery bypass graft patients: an artificial neural network prediction model.
AB  - We constructed and internally validated an artificial neural network (ANN) model
      for prediction of in-hospital major adverse outcomes (defined as death, cardiac
      arrest, coma, renal failure, cerebrovascular accident, reinfarction, or prolonged
      mechanical ventilation) in patients who received "on-pump" coronary artery bypass
      grafting (CABG) surgery. We retrospectively analyzed a 5-year CABG surgery
      database with a final study population of 563 patients. Predictive variables were
      limited to information available before the procedure, and outcome variables were
      represented only by events that occurred postoperatively. The ANN's ability to
      discriminate outcomes was assessed using receiver-operating characteristic (ROC)
      analysis and the results were compared with a multivariate logistic regression
      (LR) model and the QMMI risk score (RS) model. A major adverse outcome occurred
      in 12.3% of all patients and 18 predictive variables were identified by the ANN
      model. Pairwise comparison showed that the ANN model significantly outperformed
      the RS model (AUC = 0.886 vs.0.752, p = 0.043). However, the other two pairs, ANN
      vs. LR models (AUC = 0.886 vs. 0.807, p = 0.076) and LR vs. RS models (AUC =
      0.807 vs. 0.752, p = 0.453) performed similarly well. ANNs tend to outperform
      regression models and might be a useful screening tool to stratify CABG
      candidates preoperatively into high-risk and low-risk groups.

PMID- 14728155
TI  - An extended hierarchical task analysis for error prediction in medical devices.
AB  - This paper introduces an extended hierarchical task analysis (HTA) methodology
      devised to evaluate and compare user interfaces on volumetric infusion pumps. The
      pumps were studied along the dimensions of overall usability and propensity for
      generating human error. With HTA as our framework, we analyzed six pumps on a
      variety of common tasks using Norman's Action theory. The introduced method of
      evaluation divides the problem space between the external world of the device
      interface and the user's internal cognitive world, allowing for predictions of
      potential user errors at the human-device level. In this paper, one detailed
      analysis is provided as an example, comparing two different pumps on two separate
      tasks. The results demonstrate the inherent variation, often the cause of usage
      errors, found with infusion pumps being used in hospitals today. The reported
      methodology is a useful tool for evaluating human performance and predicting
      potential user errors with infusion pumps and other simple medical devices.

PMID- 14728156
TI  - Integrating pharmacokinetics knowledge into a drug ontology: as an extension to
      support pharmacogenomics.
AB  - The newly developed U.S. Common Medication Information Infrastructure was used as
      a basis to capture and formally express the properties of drugs relevant to
      research and the clinical application of pharmacogenomics. Two associated
      taxonomies within the model, Mechanism of Action and Physiologic Effect, were
      enriched to accommodate pharmacogenomic use-cases; the 4,000 active ingredients
      in the VA NDF-RT drug file were related to the enhanced taxonomies.
      Pharmacokinetics were independently modeled for pharmacogenomics and tested
      against thirty-one high-profile drugs to demonstrate our approach.

PMID- 14728157
TI  - Use of online resources while using a clinical information system.
AB  - BACKGROUND: Clinical information system (CIS) use is likely to evoke information
      needs, yet information resources use during CIS use has not been studied.
      METHODS: We used CIS log files and a survey to characterize clinicians' use of
      resources and infobuttons (context-sensitive links from a CIS to specific
      resources) while using a CIS. RESULTS: We examined 38,763 uses of resources and
      infobuttons by 2,607 users to identify specific sources and contexts (CIS
      functions) in which they used them. Laboratory results review was the most
      frequent context and Micromedex was the most popular resource. Differences in
      resource use were related to context and user type. The survey confirmed that
      resources and infobuttons were perceived as useful for patient-specific questions
      while using a CIS. CONCLUSIONS: Understanding context- and user-type-specific
      information needs can guide the development of infobuttons for use in a CIS.

PMID- 14728158
TI  - An architecture for standardized terminology services by wrapping and integration
      of existing applications.
AB  - Research on terminology services has resulted in development of applications and
      definition of standards, but has not yet led to widespread use of (standardized)
      terminology services in practice. Current terminology services offer
      functionality both for concept representation and lexical knowledge
      representation, hampering the possibility of combining the strengths of dedicated
      (concept and lexical) services. We therefore propose an extensible architecture
      in which concept-related and lexicon-related components are integrated and made
      available through a uniform interface. This interface can be extended in order to
      conform to existing standards, making it possible to use dedicated (third-party)
      components in a standardized way. As a proof of concept and a reference
      implementation, a SOAP-based Java implementation of the terminology service is
      being developed, providing wrappers for Protege and UMLS Knowledge Source Server.
      Other systems, such as the Description Logic-based reasoner RACER can be easily
      integrated by implementation of an appropriate wrapper.

PMID- 14728159
TI  - A general architecture for intelligent tutoring of diagnostic classification
      problem solving.
AB  - We report on a general architecture for creating knowledge-based medical training
      systems to teach diagnostic classification problem solving. The approach is
      informed by our previous work describing the development of expertise in
      classification problem solving in Pathology. The architecture envelops the
      traditional Intelligent Tutoring System design within the Unified Problem-solving
      Method description Language (UPML) architecture, supporting component modularity
      and reuse. Based on the domain ontology, domain task ontology and case data, the
      abstract problem-solving methods of the expert model create a dynamic solution
      graph. Student interaction with the solution graph is filtered through an
      instructional layer, which is created by a second set of abstract problem-solving
      methods and pedagogic ontologies, in response to the current state of the student
      model. We outline the advantages and limitations of this general approach, and
      describe it's implementation in SlideTutor - a developing Intelligent Tutoring
      System in Dermatopathology.

PMID- 14728160
TI  - Clinical information needs in context: an observational study of clinicians while
      using a clinical information system.
AB  - INTRODUCTION: The development of tools to meet the information needs of
      clinicians requires an understanding of the clinician and the context in which
      clinical decisions are being made. METHODS: We conducted an observational study
      of clinicians' information needs via think-aloud protocols during which we
      observed physicians and nurses as they used the clinical information system.
      Protocol analysis was then used to identify the information needs events, the
      types of questions that were asked, the method of meeting that need, the success
      or failure of meeting the specific information need, and the context in which it
      arose. RESULTS: Results indicated that a) unmet information needs occur
      frequently and that b) the predominant feature of these unmet needs is that they
      are patient-related or domain-specific. Two categories of context: laboratory and
      medical communication accounted for more than half of the events.

PMID- 14728161
TI  - The KnowledgeMap project: development of a concept-based medical school
      curriculum database.
AB  - We developed the KnowledgeMap (KM) system as an online, concept-based database of
      medical school curriculum documents. It uses the KM concept indexer to map full
      text documents and match search queries to concepts in the Unified Medical
      Language System (UMLS). In this paper, we describe the design of KM and report
      the first seven months of its implementation into a medical school. Despite being
      emphasized in only two first year courses and one fourth year course, students
      from all four classes used KM to search and browse documents. All faculty members
      involved with courses piloting KM used the system to upload and manage lecture
      documents. Currently, we are working with eight course directors to transition
      their courses to KM for next year.

PMID- 14728162
TI  - A prototype natural language interface to a large complex knowledge base, the
      Foundational Model of Anatomy.
AB  - We describe a constrained natural language interface to a large knowledge base,
      the Foundational Model of Anatomy (FMA). The interface, called GAPP, handles
      simple or nested questions that can be parsed to the form, subject-relation
      object, where subject or object is unknown. With the aid of domain-specific
      dictionaries the parsed sentence is converted to queries in the StruQL graph
      searching query language, then sent to a server we developed, called OQAFMA, that
      queries the FMA and returns output as XML. Preliminary evaluation shows that GAPP
      has the potential to be used in the evaluation of the FMA by domain experts in
      anatomy.

PMID- 14728163
TI  - Monitoring pharmacy expert system performance using statistical process control
      methodology.
AB  - Automated expert systems provide a reliable and effective way to improve patient
      safety in a hospital environment. Their ability to analyze large amounts of data
      without fatigue is a decided advantage over clinicians who perform the same
      tasks. As dependence on expert systems increase and the systems become more
      complex, it is important to closely monitor their performance. Failure to
      generate alerts can jeopardize the health and safety of patients, while
      generating excessive false positive alerts can lead to valid alerts being
      dismissed as noise. In this study, statistical process control charts were used
      to monitor an expert system, and the strengths and weaknesses of this technology
      are presented.

PMID- 14728164
TI  - Bioinformatics for medical diagnostics: assessment of microarray data in the
      context of clinical databases.
AB  - MOTIVATION: To identify genes suitable for medical diagnostics microarray data is
      assessed in the context of clinical databases, which store complex information
      about the patient phenotype. The wealth of data and lacking standards make it
      difficult to analyse this kind of data. RESULTS: We present a workflow for
      exploratory analysis of microarray data together with clinical data consisting of
      four steps: definition of clinically meaningful research questions in a
      masterfile, generation of analysis files, selection and characterization of
      differentially expressed genes, and estimation of classification accuracy. We
      applied this workflow to large data sets from the field of cardiology and
      oncology (n~500 patients). Systematic data management of microarray data and
      clinical data helps to make results more transparent and comparable.

PMID- 14728165
TI  - Telephone triage: a timely data source for surveillance of influenza-like
      diseases.
AB  - We evaluated telephone triage (TT) data for public health early warning systems.
      TT data is electronically available and contains coded elements that include the
      demographics and description of a caller's medical complaints. In the study, we
      obtained emergency room TT data and after hours TT data from a commercial TT
      software and service company. We compared the timeliness of the TT data with
      influenza surveillance data from the Centers for Disease Control using the cross
      correlation function. Emergency room TT calls are one to five weeks ahead of
      surveillance data collected by the CDC.

PMID- 14728167
TI  - What is the prevalence of health-related searches on the World Wide Web?
      Qualitative and quantitative analysis of search engine queries on the internet.
AB  - While health information is often said to be the most sought after information on
      the web, empirical data on the actual frequency of health-related searches on the
      web are missing. In the present study we aimed to determine the prevalence of
      health-related searches on the web by analyzing search terms entered by people
      into popular search engines. We also made some preliminary attempts in
      qualitatively describing and classifying these searches. Occasional difficulties
      in determining what constitutes a "health-related" search led us to propose and
      validate a simple method to automatically classify a search string as "health
      related". This method is based on determining the proportion of pages on the web
      containing the search string and the word "health", as a proportion of the total
      number of pages with the search string alone. Using human codings as gold
      standard we plotted a ROC curve and determined empirically that if this "co
      occurance rate" is larger than 35%, the search string can be said to be health
      related (sensitivity: 85.2%, specificity 80.4%). The results of our "human"
      codings of search queries determined that about 4.5% of all searches are "health
      related". We estimate that globally a minimum of 6.75 Million health-related
      searches are being conducted on the web every day, which is roughly the same
      number of searches that have been conducted on the NLM Medlars system in 1996 in
      a full year.

PMID- 14728166
TI  - Comprehensive categorization of guideline recommendations: creating an action
      palette for implementers.
AB  - Transforming guideline recommendations into executable statements for
      computerized decision support systems requires a clear understanding of what
      tasks must be performed. We sought (a) to determine whether a limited set of
      action types could be defined to comprehensively categorize activities
      recommended by the majority of clinical guidelines, (b) to describe the relative
      frequency of these action types, and (c) to create a library of recommendations
      for future validation activities. We randomly selected test and validation sets
      of 50 recommendations each from the National Guideline Clearinghouse and randomly
      extracted 3 recommendations from each guideline. We tested the ability of a
      preliminary palette of action types to categorize guideline-prescribed activities
      and expanded it to accommodate several unanticipated actions. Ultimately, the
      following actions were sufficient to categorize all 405 actions: Prescribe,
      Perform therapeutic procedure, Educate/Counsel, Test, Dispose, Refer/Consult,
      Conclude, Monitor, Document, Advocate, Prepare, and No recommendation., and
      Prepare. Thus, we define a set of terms that can facilitate guideline
      implementation in clinical information systems. These action types can be used to
      construct a framework for design of clinical decision support systems.

PMID- 14728168
TI  - Feasibility and patients' acceptance of Home Automated Telemanagement of oral
      anticoagulation therapy.
AB  - We developed the Home Automated Telemanagement (HAT) system for patients on oral
      anticoagulation therapy. It consists of a home unit, HAT server, and clinician
      unit. Patients at home use a palmtop or a laptop connected with a prothrombin
      time (PT) monitor. Each HAT session consists of self-testing, feedback, and
      educational components. The symptom data and PT/INR from patient homes are
      automatically sent to the HAT server and analyzed by the system. Patients who
      were seen in the Anticoagulation Clinic (N=29) were asked to use HAT in a
      laboratory setting. Semi-structured, in-depth interviews were used for the
      evaluation of HAT acceptance. 93% claimed that they would use such a tool at home
      and would advise other patients to use HAT for self-management and disease
      specific education. Twelve patients used HAT at home for eight weeks. Compared to
      baseline, patients completing the home study showed statistically significant
      improvement in disease-specific quality of life dimensions of general
      satisfaction, self-efficacy, daily hassles, and distress. The Client Satisfaction
      Questionnaire demonstrated significant improvement in patient satisfaction with
      the treatment process. Our results demonstrated high acceptance of the HAT system
      by patients receiving long term anticoagulation therapy regardless of their
      previous computer experience or socioeconomic background.

PMID- 14728169
TI  - Community clinical data exchange for emergency medicine patients.
AB  - Little is known about the opportunities for a community clinical data exchange
      network to influence patient care. Rates of patient "cross-over" among different
      institutions can provide one estimate of the additional value such systems have
      over unconnected, independent institutional electronic medical records. The
      Indiana Network for Patient Care (INPC) represents such a system, involving a
      collaboration of central Indiana hospitals to improve patient care. During a one
      year study period, 288,696 patients made 471,640 Emergency Department (ED) visits
      within the INPC collaboration -- accounting for 92% of all Indianapolis ED
      visits. Overall 25% of the patients with more than one visit also visited one of
      the other five hospital systems, accounting for 19% of all visits. Our results
      help clarify the expected frequency within one large metropolitan area that ED
      patients could obtain direct benefit from a community clinical data exchange
      network.

PMID- 14728170
TI  - Integrating a hypernymic proposition interpreter into a semantic processor for
      biomedical texts.
AB  - Semantic processing provides the potential for producing high quality results in
      natural language processing (NLP) applications in the biomedical domain. In this
      paper, we address a specific semantic phenomenon, the hypernymic proposition, and
      concentrate on integrating the interpretation of such predications into a more
      general semantic processor in order to improve overall accuracy. A preliminary
      evaluation assesses the contribution of hypernymic propositions in providing more
      specific semantic predications and thus improving effectiveness in retrieving
      treatment propositions in MEDLINE abstracts. Finally, we discuss the
      generalization of this methodology to additional semantic propositions as well as
      other types of biomedical texts.

PMID- 14728171
TI  - Will decision support in medications order entry save money? A return on
      investment analysis of the case of the Hong Kong hospital authority.
AB  - The computerized medications order entry system currently used in the public
      hospitals of Hong Kong does not have decision support features. Plans are
      underway to add decision support to this system to alert physicians on drug
      allergy conflicts, drug-lab result conflicts, drug-drug interactions and atypical
      dosages. A return on investment analysis is done on this enhancement, both as an
      examination of whether there is a positive return on the investment and as a
      contribution to the ongoing discussion of the use of return on investment models
      in health care information technology investments. It is estimated that the
      addition of decision support will reduce adverse drug events by 4.2 - 8.4%. Based
      on this estimate, a total net saving of $44,000 - $586,000 is expected over five
      years. The breakeven period is estimated to be between two to four years.

PMID- 14728172
TI  - Telemedicine in Western Africa: lessons learned from a pilot project in Mali,
      perspectives and recommendations.
AB  - OBJECTIVE: to evaluate the feasibility, potential and risks of an internet-based
      telemedicine network in developing countries of Western Africa. METHODS: a
      project for the development of a national telemedicine network in Mali was
      initiated in 2001, using internet-based technologies for distance learning and
      teleconsultations. RESULTS: the telemedicine network has been in productive use
      for 12 months and has enabled various collaboration channels, including North
      South, South-South, and South-North distance learning and teleconsultations. It
      also unveiled a set of potential problems: a) limited pertinence of North-South
      collaborations when there are major differences in available resources or socio
      cultural contexts between the collaborating parties; b) risk of induced digital
      divide if the periphery of the health system is not involved in the development
      of the network, and c) need for the development of local medical contents
      management skills. CONCLUSION: the identified risks must be taken into account
      when designing large-scale telemedicine projects in developing countries and can
      be mitigated by the fostering of South-South collaboration channels, the use of
      satellite-based internet connectivity in remote areas, and the valorization of
      local knowledge and its publication on-line.

PMID- 14728173
TI  - Does GEM-encoding clinical practice guidelines improve the quality of knowledge
      bases? A study with the rule-based formalism.
AB  - The aim of this work was to determine whether the GEM-encoding step could improve
      the representation of clinical practice guidelines as formalized knowledge bases.
      We used the 1999 Canadian recommendations for the management of hypertension,
      chosen as the knowledge source in the ASTI project. We first clarified semantic
      ambiguities of therapeutic sequences recommended in the guideline by proposing an
      interpretative framework of therapeutic strategies. Then, after a formalization
      step to standardize the terms used to characterize clinical situations, we
      created the GEM-encoded instance of the guideline. We developed a module for the
      automatic derivation of a rule base, BR-GEM, from the instance. BR-GEM was then
      compared to the rule base, BR-ASTI, embedded within the critic mode of ASTI, and
      manually built by two physicians from the same Canadian guideline. As compared to
      BR-ASTI, BR-GEM is more specific and covers more clinical situations. When
      evaluated on 10 patient cases, the GEM-based approach led to promising results.

PMID- 14728174
TI  - Analysis of a probabilistic record linkage technique without human review.
AB  - We previously developed a deterministic record linkage algorithm demonstrating
      sensitivities approaching 90% while maintaining 100% specificity. Substantially
      better performance has been reported using probabilistic linkage techniques;
      however, such methods often incorporate human review into the process. To avoid
      human review, we employed an estimator function using the Expectation
      Maximization (EM) algorithm to establish a single true-link threshold. We
      compared the unsupervised probabilistic results against the manually reviewed
      gold-standard for two hospital registries, as well against our previous
      deterministic results. At an estimated specificity of 99.95%, actual
      specificities were 99.43% and 99.42% for registries A and B, respectively. At an
      estimated sensitivity of 99.95%, actual sensitivities were 99.19% and 98.99% for
      registries A and B, respectively. The EM algorithm estimated linkage parameters
      with acceptable accuracy, and was an improvement over the deterministic
      algorithm. Such a methodology may be used where record linkage is required, but
      human intervention is not possible or practical.

PMID- 14728175
TI  - Optimizing spectral power compression with respect to inference performance for
      recognition of tumor patterns in ultrasound images.
AB  - Imaging modalities are widely used to explore and diagnose diseases. Feature
      extraction methods are used to quantitatively describe and identify objects of
      interest in acquired images, typically involving data compression. The extracted
      features are subject to clinical inference, whereby the compression ratio used
      for feature extraction can affect the inference performance. In this paper, a new
      method is introduced which allows for optimal data compression with respect to
      performance maximization of uncertain inference. The model introduced herein
      identifies objects of interest using selective data compression in the frequency
      domain. It quantifies the amount of information provided by the inference
      involving these objects, calculates the inference efficiency, and estimates its
      cost. By analyzing the effect of data compression on inference efficiency and
      cost, the method allows for the optimal selection of the compression ratio. The
      method is applied to prostate cancer diagnosis in ultrasound images.

PMID- 14728176
TI  - Are electronic medical records trustworthy? Observations on copying, pasting and
      duplication.
AB  - As routine use of on-line progress notes in US Department of Veterans Affairs
      facilities grew rapidly in the past decade, health information managers and
      clinicians began to notice that authors sometimes copied text from old notes into
      new notes. Other sources of duplication were document templates that inserted
      boilerplate text or patient data into notes. Word-processing and templates aided
      the transition to electronic notes, but enabled author copying and sometimes led
      to lengthy, hard-to-read records stuffed with data already available on-line.
      Investigators at a VA center recognized for pioneering a fully electronic record
      system analyzed author copying and template-generated duplication with adapted
      plagiarism-detection software. Nine percent of progress notes studied contained
      copied or duplicated text. Most copying and duplication was benign, but some
      introduced misleading errors into the record and some seemed possibly unethical
      or potentially unsafe. High-risk author copying occurred once for every 720
      notes, but one in ten electronic charts contained an instance of high-risk
      copying. Careless copying threatens the integrity of on-line records. Clear
      policies, practitioner consciousness-raising and development of effective
      monitoring procedures are recommended to protect the value of electronic patient
      records.

PMID- 14728177
TI  - Testing the generalizability of the ISO model for nursing diagnoses.
AB  - The purpose of this study was to explore whether the ISO reference terminology
      model for nursing diagnoses could be generalized to the MDS data set that, like
      nursing terminologies standardizes expressions of the concepts within and
      relevant to the domain of nursing practice. We first constructed paraphrased
      expressions of the rubrics from the data set. Next we dissected those expressions
      into the reference model domains of focus and judgment, recorded any qualifiers
      required for either domain, and semantic links required to represent associative
      relations. Our findings demonstrate that the ISO model for nursing diagnoses is
      generalizable to the MDS data set, however expansions to the model are required
      if the model is to be used to represent objects rather than terms.

PMID- 14728178
TI  - Enhancing quality of retrieval through concept edit history.
AB  - The NCI Thesaurus is a public domain description logic-based terminology produced
      by the National Cancer Institute. The NCI Thesaurus is used to support storage
      and retrieval of scientific, clinical and research administration data. The
      content of the NCI Thesaurus evolves rapidly. We have developed a representation
      of concept change over time and have implemented software to capture concept
      change in our multi-editor concurrent vocabulary development environment. We are
      now implementing software to extend our vocabulary server, public APIs and our
      file-based distributions of the Thesaurus to provide access to the concept-level
      history information.

PMID- 14728179
TI  - How the ICU follows orders: care delivery as a complex activity system.
AB  - In this paper, we use the theory of distributed cognition to understand work
      practices in terms of the behavior of an activity system. We do so by detailing
      the roles that local representations of information play in the social,
      cognitive, organizational, and technological processes that accomplish task work.
      Specifically, we characterize a portion of the medication order process in an
      Intensive Care Unit. In this setting, the processes that execute a medication
      order have evolved to accomplish the primary tasks of medication administration
      and also to simultaneously support other important aspects of the unit's work.
      Designers of systems that centralize and automate information resources must
      consider the diverse and latent roles played by information in order to improve
      design and to anticipate how their products affect complex care delivery systems.

PMID- 14728180
TI  - Multiscale analysis of long time-series medical databases.
AB  - Data mining in time-series medical databases has been receiving considerable
      attention since it provides a way of revealing useful information hidden in the
      database; for example relationships between the temporal course of examination
      results and onset time of diseases. This paper presents a new method for finding
      similar patterns in temporal sequences based on multiscale matching. Multiscale
      matching enables us the cross-scale comparison of sequences, namely, it enable us
      to compare temporal patterns by partially changing observation scales. We
      examined the usefulness of the method on the chronic hepatitis dataset and found
      some interesting patterns. On GPT sequences, we found patterns that may represent
      the effectiveness of interferon (IFN) treatment. On platelet count sequences, we
      found that, if IFN treatment was ineffective, platelet count kept decreasing
      following the progress of liver fibrosis, while it started increasing if the
      treatment was effective.

PMID- 14728181
TI  - The cognitive complexity of a provider order entry interface.
AB  - Computer-based provider order entry (POE) can reduce the frequency of preventable
      medical errors. However, overly complex interfaces frequently pose a challenge to
      users and impede clinical efficacy. We present a cognitive analysis of clinician
      interaction with a commercial POE system. Our investigation was informed by the
      distributed resources model, a novel approach designed to describe the dimensions
      of user interfaces that introduce unnecessary cognitive complexity. This approach
      characterizes the relative distribution of user's internal representations and
      external representations embodied in the system or environmental artifacts. The
      research consisted of two component analyses: a modified cognitive walkthrough
      evaluation and a simulated clinical ordering task performed by seven physicians.
      The analysis revealed that the configuration of resources placed unnecessarily
      heavy cognitive demands on the user, especially those who lacked a robust
      conceptual model of the system. The resources model was also used to account for
      patterns of errors produced by clinicians.

PMID- 14728182
TI  - Patient perceptions of physician use of handheld computers.
AB  - BACKGROUND: Handheld computers have advantages for healthcare providers including
      portability and integration into office workflow. However, negative patient
      perceptions of physician use of handheld computers in the examining room might
      limit integration. OBJECTIVE: To survey patients' perceptions of handheld use,
      and compare those with their providers' perceptions. METHODS: A survey of patient
      attitudes toward handhelds was conducted among patients at a low-income
      university clinic. Internal Medicine residents providing care were also surveyed.
      RESULTS: Patients (N=93) were mostly female (79%) and ethnic minorities (67%)
      with average age of 39. Only 10% of patients did not like the idea of a handheld
      computer in the exam room. Other negative attitudes were also seen in a minority
      of patients. Some physicians (23%) reported reservations about using the handheld
      computer with patients. CONCLUSIONS: Negative attitudes were rare among patients,
      but some providers were concerned about using the handheld in the exam room.

PMID- 14728183
TI  - A proposed ontology for online healthcare surveys.
AB  - This paper results from the research efforts of the Clinical Informatics Research
      Group in building a generalized system for online survey implementation. Key to
      the success of any generalized survey system is a standard ontology for the
      differing components of any survey, particularly those sought to be implemented
      online, over the World Wide Web. In this paper, we introduce the need for
      generalized survey authoring tools, discuss our methods for elucidating the
      different components present in many healthcare instruments and classifying them
      as per existing standards, and later present our proposed ontology for online
      surveys in the healthcare domain. This is followed by a more detailed description
      of the different question types mentioned in this ontology. Finally, we compare
      some general purpose authoring systems currently available to determine their
      flexibility in representing these disparate question types
      (www.cirg.washington.edu/SuML).

PMID- 14728184
TI  - Critical gaps in the world's largest electronic medical record: Ad Hoc nursing
      narratives and invisible adverse drug events.
AB  - The Veterans Health Administration (VHA), of the U.S. Department of Veteran
      Affairs, operates one of the largest healthcare networks in the world. Its
      electronic medical record (EMR) is fully integrated into clinical practice,
      having evolved over several decades of design, testing, trial, and error. It is
      unarguably the world's largest EMR, and as such it makes an important case study
      for a host of timely informatics issues. The VHA consistently has been at the
      vanguard of patient safety, especially in its provider-oriented EMR. We describe
      here a study of a large set of adverse drug events (ADEs) that eluded a rigorous
      ADE survey based on prospective EMR chart review. These numerous ADEs were
      undetected (and hence invisible) in the EMR, missed by an otherwise sophisticated
      ADE detection scheme. We speculate how these invisible nursing ADE narratives
      persist and what they portend for safety re-engineering.

PMID- 14728185
TI  - Dimension reduction for physiological variables using graphical modeling.
AB  - In intensive care, physiological variables of the critically ill are measured and
      recorded in short time intervals. The proper extraction and interpretation of the
      essential information contained in this flood of data can hardly be done by
      experience alone. Typically, decision making in intensive care is based on only a
      few selected variables. Alternatively, for a dimension reduction statistical
      latent variable techniques like principal component analysis or factor analysis
      can be applied. However, the interpretation of latent components extracted by
      these methods may be difficult. A more refined analysis is needed to provide
      suitable bedside decision support. Graphical models based on partial correlations
      provide information on the relationships among physiological variables that is
      helpful for variable selection and for identifying interpretable latent
      components. In a comparative study we investigate how much of the variability of
      the observed multivariate physiological time series can be explained by variable
      selection, by standard principal component analysis and by extracting latent
      compo-nents from groups of variables identified in a graphical model.

PMID- 14728186
TI  - Detection of pediatric respiratory and gastrointestinal outbreaks from free-text
      chief complaints.
AB  - We conducted a retrospective study to ascertain the potential of free-text chief
      complaints collected in pediatric emergency departments to serve as surveillance
      data for early detection of outbreaks. We determined that automatically coded
      chief complaint data provide a signal that reflects outbreaks in a population of
      children less than five years of age. Using the Exponentially Weighted Moving
      Average (EWMA) detection algorithm, we measured the timeliness, sensitivity, and
      specificity of free-text chief complaints for predicting outbreaks of pediatric
      respiratory and gastrointestinal illness. We found that time series of
      automatically coded free text-chief complaints in pediatric patients correlate
      well with hospital admissions and precede them by the mean of 10.3 days (95% CI 
      15.15, 35.5) for respiratory outbreaks and 29 days (95% CI 4.23, 53.7) for
      gastrointestinal outbreaks. We conclude that free-text chief complaints may play
      an important role as an early, sensitive and specific indicator of outbreaks of
      respiratory and gastrointestinal illness in children less than five years of age.

PMID- 14728187
TI  - Making the standard more standard: a data and query model for knowledge
      representation in the Arden syntax.
AB  - CONTEXT: Arden Syntax is a Health Level Seven (HL7) standard that can be used to
      encode computable knowledge. However, dissemination of knowledge is hampered by
      lack of standard database linkages in Arden knowledge bases (KB). Moreover, the
      HL7 Reference Information Model (RIM) is object-oriented and hence incompatible
      with the current Arden data model. Also, significant investment has been made in
      Arden KBs that would be lost if a backward-incompatible data model were adopted.
      OBJECTIVE: To define a data model that standardizes database linkages and
      provides object-oriented features while maintaining backward compatibility.
      ANALYSIS: We identified the objects of the RIM that could be used as a schema for
      standard database queries. We propose extensions to Arden to accommodate this
      model, including the manipulation of objects. CONCLUSION: A data model that
      standardizes database linkages and introduces object-oriented constructs will
      facilitate knowledge transfer without violation of backward compatibility in the
      Arden Syntax.

PMID- 14728188
TI  - Randomized comparisons among health informatics students identify hypertutorial
      features as improving web-based instruction.
AB  - Hypertutorials optimize five features - presentation, learner control, practice,
      feedback, and elaborative learning resources. Previous research showed graduate
      students significantly and overwhelmingly preferred Web-based hypertutorials to
      conventional "Book-on-the-Web" statistics or research design lessons. The current
      report shows that the source of hypertutorials' superiority in student
      evaluations of instruction lies in their hypertutorial features. Randomized
      comparisons between the two methodologies were conducted in two successive
      iterations of a graduate level health informatics research design and evaluation
      course. The two versions contained the same text and graphics, but differed in
      the presence or absence of hypertutorial features: Elaborative learning
      resources, practice, feedback, and amount of learner control. Students gave high
      evaluations to both Web-based methodologies, but consistently rated the
      hypertutorial lessons as superior. Significant differences localized in the
      hypertutorial subscale that measured student responses to hypertutorial features.

PMID- 14728189
TI  - A framework for the biomedical informatics curriculum.
AB  - The problem of developing a curriculum for biomedical informatics is highly
      dependent on how we choose to define and practice the field. Numerous authors
      have questioned how to position biomedical informatics along the continuum of
      formal, empirical and engineering disciplines. A concern with current educational
      programs in biomedical informatics is that students finish without a clear
      understanding of the relation between theory and practice, or worse, with the
      impression that the field does not possess any theoretical basis. In this paper,
      we propose that biomedical informatics curricula explicitly address skills and
      competencies at three levels: formal, empirical, and applied. We posit that that
      knowledge of formalization is necessary to build testable empirical models, and
      that model-driven approaches are necessary for deploying information systems that
      can be evaluated in a meaningful way. A curricular framework is proposed that
      identifies a set of methods, techniques and theories that have broad
      applicability within the domain of biomedicine, and which can span a wide range
      of application areas: bioinformatics, imaging informatics, clinical informatics
      and public health informatics. A stronger linkage between theory and practice
      will result in students who are empowered to create effective and lasting
      solutions to biomedical problems.

PMID- 14728190
TI  - Information warehouse as a tool to analyze Computerized Physician Order Entry
      order set utilization: opportunities for improvement.
AB  - A Computerized Physician order entry (CPOE) system was successfully implemented
      at the Ohio State University Medical Center (OSUMC) in February 2000. The
      electronic entry and use of order sets is designed to standardize patient care
      and improve efficiency and patient safety. To evaluate the effectiveness of the
      CPOE system and to maximize its benefits, one needs to easily access and analyze
      the data. Since the CPOE system is not equipped to support such on demand
      analysis, the data from the system is extracted daily into the OSUMC's
      Information Warehouse (IW). This allows the CPOE data to be linked with other
      clinical and financial patient information in the IW to provide detailed and
      comprehensive analysis. Our focus in this paper is the use of the IW as a tool to
      analyze order set usage patterns and the opportunities such analysis provides for
      improvements in education, resource utilization and patient care.

PMID- 14728191
TI  - Discharge communique: use of a workflow byproduct to generate an interim
      discharge summary.
AB  - Medical problems left unresolved during hospitalizations (along with recommended
      outpatient evaluations, test results pending at discharge, and discharge
      medication regimens) are often documented in patients' discharge summaries.
      However, studies have demonstrated that discharge summaries are frequently
      unavailable or inaccessible at post discharge visit(s). Interim discharge
      summaries have been shown to improve the flow of information between inpatient
      and outpatient physicians. We have constructed a web-based solution, discharge
      communiques that are very much like interim discharge summaries but are an
      automatic byproduct of an every day workflow process, signout. The New SignOut
      System captures signout information and generates discharge communiques
      immediately upon discharge. From June 2002-January 2003 7926 discharge
      communiques were made available on 7926 patients and there were 12,920 look-ups
      of communiques. Studies concur that 40-50% of patients will not have an available
      discharge summary making communiques the primary source of clinical information
      on prior hospitalization for outpatient physicians.

PMID- 14728192
TI  - Deriving design recommendations through discount usability engineering:
      ethnographic observation and thinking-aloud protocol in usability testing for
      computer-based teaching cases.
AB  - Usability engineering often involves experimental evaluation designs carried out
      in special usability laboratories. Though becoming more popular in medical
      informatics, the approach is little used. Possibly this is because of the expense
      involved in set-up, data collection, and data analysis. Excellent results may be
      obtained, however, by employing discount usability engineering and qualitative
      methods of data collection and analysis to generate recommendations to improve
      usability. A prototype computer-based teaching case was evaluated in a discount
      usability engineering approach by combining modified ethnographic observation
      with simplified thinking aloud protocol. Data was collected and analyzed using
      standard approaches for qualitative data. This approach led to helpful
      recommendations for designing teaching cases. The project team believes this
      economical approach to usability testing may be helpful to others engaged in
      interface design.

PMID- 14728193
TI  - The UMLS Semantic Network and the Semantic Web.
AB  - The Unified Medical Language System is an extensive source of biomedical
      knowledge developed and maintained by the US National Library of Medicine (NLM)
      and is being currently used in a wide variety of biomedical applications. The
      Semantic Network, a component of the UMLS is a structured description of core
      biomedical knowledge consisting of well defined semantic types and relationships
      between them. We investigate the expressiveness of DAML+OIL, a markup language
      proposed for ontologies on the Semantic Web, for representing the knowledge
      contained in the Semantic Network. Requirements specific to the Semantic Network,
      such as polymorphic relationships and blocking relationship inheritance are
      discussed and approaches to represent these in DAML+OIL are presented. Finally,
      conclusions are presented along with a discussion of ongoing and future work.

PMID- 14728194
TI  - A cognitive framework for understanding barriers to the productive use of a
      diabetes home telemedicine system.
AB  - Telemedicine has the potential to transcend geographic and socio-cultural
      barriers to the delivery of high quality health care to the medically underserved
      populations. However, there are significant cognitive and usability barriers.
      This paper presents a multifaceted cognitive evaluation of the IDEATel diabetes
      education and telemedicine program. The evaluation included a cognitive
      walkthrough analysis to characterize task complexity and identify potential
      problems as well as field usability testing in patients' homes. The study
      revealed dimensions of the interface that impeded optimal access to system
      resources. In addition, we found significant obstacles corresponding to
      perceptual-motoric skills, mental models of the system, and health literacy. The
      objective of this work is to contribute to a design framework so that
      participants with a wide range of skills can better manage their chronic
      illnesses.

PMID- 14728195
TI  - Clinical decision support provided within physician order entry systems: a
      systematic review of features effective for changing clinician behavior.
AB  - Computerized physician order entry (CPOE) systems represent an important tool for
      providing clinical decision support. In undertaking this systematic review, our
      objective was to identify the features of CPOE-based clinical decision support
      systems (CDSSs) most effective at modifying clinician behavior. For this review,
      two independent reviewers systematically identified randomized controlled trials
      that evaluated the effectiveness of CPOE-based CDSSs in changing clinician
      behavior. Furthermore, each included study was assessed for the presence of 14
      CDSS features. We screened 10,023 citations and included 11 studies. Of the 10
      studies comparing a CPOE-based CDSS intervention against a non-CDSS control
      group, 7 reported a significant desired change in professional practice.
      Moreover, meta-regression analysis revealed that automatic provision of the
      decision support was strongly associated with improved professional practice
      (adjusted odds ratio, 23.72; 95% confidence interval, 1.75-infiniti). Thus, we
      conclude that automatic provision of decision support is a critical feature of
      successful CPOE-based CDSS interventions.

PMID- 14728196
TI  - One-on-one proficiency training: an evaluation of satisfaction and effectiveness
      using clinical information systems.
AB  - OBJECTIVE: To examine the effectiveness of a one-on-one training method for
      advanced proficiency in the use of clinical information systems (CIS) by
      clinicians (physicians, physician assistants, and nurse practitioners) in a large
      HMO. DESIGN: A cross-sectional survey of 129 clinicians. MEASUREMENTS:
      Satisfaction was measured using a multi-item satisfaction index. Perceived
      effectiveness of the training was measured by assessing self-reported
      improvements in efficiency in CIS. RESULTS: Response rate of 80%. The one-on-one
      method was significantly preferred over any other teaching methods (p<.0001).
      Improvement in use of the electronic medical record was greatest following one-on
      one training when compared to other CIS components. Major improvements (i.e., >3
      on 5 point Likert scale) in use of the electronic medical record were reported by
      61.4% of the clinicians. Overall satisfaction was significantly higher among
      women (p<.05). CONCLUSION: The findings support the assumption that one-on-one
      training is of value to clinicians and that this training modality is valued
      above other methods.

PMID- 14728197
TI  - Functional relationships between gene pairs in oral squamous cell carcinoma.
AB  - We developed a novel method for the discovery of functional relationships between
      pairs of genes based on gene expression profiles generated from microarrays. This
      approach examines all possible pairs of genes and identifies those in which the
      relationship between the two genes changes in different diseases or conditions.
      In contrast to previous methods that have focused on differentially expressed
      genes, this method attempts to find changes in the correlation between genes.
      These changes may be indicative of the functional relationships related to a
      disease mechanism. We demonstrate the utility of this approach by applying it to
      an oral squamous cell carcinoma (OSCC) microarray data set. Our results suggest
      new directions for future experimental investigations.

PMID- 14728198
TI  - Creating an enterprise-wide allergy repository at Partners HealthCare System.
AB  - A significant fraction of medication errors and preventable adverse drug events
      are related to drug-allergy interactions (DAIs). Computerized prescribing can
      help prevent DAIs, but an accurate record of the patient's allergies is required.
      At Partners HealthCare System in Boston, the patient's allergy list is
      distributed across several applications including computer physician order entry
      (CPOE), the outpatient medical record, pharmacy applications, and nurse charting
      applications. Currently, each application has access only to its own allergy
      data. This paper presents details of a project designed to integrate the various
      allergy repositories at Partners. We present data documenting that patients have
      allergy data stored in multiple repositories. We give detail about issues we are
      encountering such as which applications should participate in the repository,
      whether "NKA" or "NKDA" should be used to document known absence of allergies,
      and which personnel should be allowed to enter allergies. The issues described in
      this paper may well be faced by other initiatives intended to create
      comprehensive allergy repositories.

PMID- 14728199
TI  - From prototype to production system: lessons learned from the evolution of the
      SignOut System at Mount Sinai Medical Center.
AB  - Approaches to the development of information systems in large health care
      institutions range from prototyping to conventional development of large scale
      production systems. This paper discusses the development of the SignOut System at
      Mount Sinai Medical Center, which was designed in 1997 to capture vital resident
      information. Local need quickly outstripped proposed delays for building a
      production system and a prototype system quickly became a production system. By
      the end of 2002 the New SignOut System was built to create an integrated
      application that was a true production system. In this paper we discuss the
      design and implementation issues in moving from a prototype to a production
      system. The production system had a number of advantages, including increased
      organizational visibility, integration into enterprise resource planning and full
      time staff for support. However, the prototype allowed for more rapid design and
      subsequent changes, less training, and equal to or superior help desk support. It
      is argued that healthcare IT systems may need characteristics of both prototype
      and production system development to rapidly meet the changing and different
      needs of healthcare user populations.

PMID- 14728200
TI  - A pan-Canadian health informatics education strategy.
AB  - Despite the fact that health informatics (HI) educational opportunities in Canada
      have increased by 40% over the last 3 years, there are few opportunities for
      advanced research or credentialing at the MSc and PhD levels. Existing programs
      are also not easily accessible to working health care professionals, who require
      flexible, non-traditional delivery options for basic to advanced HI training.
      This strategy report proposes an overall vision, 3 goals, 4 tactical initiatives
      and a set of action items to improve the effectiveness of HI education in Canada

PMID- 14728201
TI  - Evaluation of a tool to categorize patients by reading literacy and computer
      skill to facilitate the computer-administered patient interview.
AB  - Past efforts to collect clinical information directly from patients using
      computers have had limited utility because these efforts required users to be
      literate and facile with the computerized information collecting system. In this
      paper we describe the creation and use of a computer-based tool designed to
      assess a user's reading literacy and computer skill for the purpose of adapting
      the human-computer interface to fit the identified skill levels of the user. The
      tool is constructed from a regression model based on 4 questions that we
      identified in a laboratory study to be highly predictive of reading literacy and
      2 questions predictive of computer skill. When used in 2 diverse clinical
      practices the tool categorized low literacy users so that they received
      appropriate support to enter data through the computer, enabling them to perform
      as well as high literacy users. Confirmation of the performance of the tool with
      a validated reading assessment instrument showed a statistically significant
      difference (p=0.0025) between the two levels of reading literacy defined by the
      tool. Our assessment tool can be administered through a computer in less than two
      minutes without requiring any special training or expertise making it useful for
      rapidly determining users' aptitudes.

PMID- 14728202
TI  - Clinical documents: attribute-values entity representation,context, page layout
      and communication.
AB  - This paper presents how acquisition, storage and communication of clinical
      documents is implemented at the University Hospitals of Geneva. Careful attention
      has been given to user-interfaces, in order to support complex layouts, spell
      checking, and templates management with automatic prefilling. A dual architecture
      has been developed for storage using an entity-attribute-value unified database
      and a consolidated, patient-centered, layout-respectful file-based storage,
      providing both representation power and speed of access. This architecture allows
      a great flexibility for storing a continuum of data types, ranging from simple
      typed values to complex clinical reports. Finally, communication is entirely
      based on HTTP-XML internally, and a HL-7 CDA interface V2 is currently studied
      for external communication. Some of the problems encountered, mostly related to
      the typology of documents and the ontology of clinical attributes are evoked.

PMID- 14728203
TI  - Evaluation of the medication sketch artist, a new method of determining unknown
      patient medications.
AB  - Medication errors are responsible for a significant number of hospital
      admissions, and significant morbidity and mortality. Many of these errors result
      from differences in physicians' and patients' understanding of medications.
      Health care providers think in terms of medication name and dose, however
      patients remember size, shape, and markings of their medications more frequently
      than the names. The Medication Sketch Artist was developed to be a graphically
      interfaced medication identification system to aid in physician-patient
      communication. This pilot study evaluated the software's ability to identify
      medications described from memory by volunteers. Out of 25 pills, each described
      5 separate times, there were 80 correct identifications, and 9 identifications of
      the correct medication, but at a different dose. The Medication Sketch Artist
      shows promise as a tool to determine unknown medications. It could play an
      important role in reducing medication errors.

PMID- 14728204
TI  - Why don't physicians use their personal digital assistants?
AB  - As the Personal Digital Assistant (PDA) user population continues to expand,
      there is a need to design more useful devices and applications to facilitate the
      utilization of PDAs. We conducted a structured interview study to examine PDA
      usage and non-usage patterns among physicians. The purpose of this descriptive
      study was to identify the barriers that impede physicians in their PDA use. A
      data collection tool was developed to record: 1) how physicians use their PDAs,
      2) functions and applications used, 3) functions and applications not used, 4)
      reasons and examples of why physicians don't use PDAs for those functions, and 5)
      the recall of specific incidents of PDA usage using Critical Incident Technique
      (CIT). Interview data were transcribed and analyzed. Study findings and how those
      barriers can be addressed are discussed.

PMID- 14728205
TI  - A framework for infection control surveillance using association rules.
AB  - Surveillance of antibiotic resistance and nosocomial infections is one of the
      most important functions of a hospital infection control program. We employed the
      association rule method for automatically identifying new, unexpected, and
      potentially interesting patterns in hospital infection control. We hypothesized
      that mining for low-support, low-confidence rules would detect unexpected
      outbreaks caused by a small number of cases. To build a framework, we
      preprocessed the data and added new templates to eliminate uninteresting
      patterns. We applied our method to the culture data collected over 3 months from
      10 hospitals in the UPMC Health System. We found that the new process and system
      are efficient and effective in identifying new, unexpected, and potentially
      interesting patterns in surveillance data. The clinical relevance and utility of
      this process await the results of prospective studies.

PMID- 14728206
TI  - Citizen centered health and lifestyle management via interactive TV: The PANACEIA
      ITV health system.
AB  - In the context of an IST European project with acronym PANACEIA-ITV, a home care
      service provisioning system is described, based on interactive TV technology. The
      purpose of PANACEIA-ITV is to facilitate essential lifestyle changes and to
      promote compliance with scientifically sound self-care recommendations, through
      the application of interactive digital television for family health maintenance.
      The means to achieve these goals are based on technological, health services and
      business models. PANACEIA-ITV is looking for communication of monitoring micro
      devices with I-TV set-top-boxes using infrared technology, and embodiment of
      analogous H/W and S/W in the I-TV set-top-boxes. Intelligent agents are used to
      regulate data flow, user queries as well as service provisions from and to the
      household through the satellite digital platform, the portal and the back-end
      decision support mechanisms, using predominantly the Active Service Provision
      (ASP) model. Moreover, interactive digital TV services are developed for the
      delivery of health care in the home care environment.

PMID- 14728207
TI  - Automated extraction and normalization of findings from cancer-related free-text
      radiology reports.
AB  - We describe the performance of a particular natural language processing system
      that uses knowledge vectors to extract findings from radiology reports. LifeCode
      (A-Life Medical, Inc.) has been successfully coding reports for billing purposes
      for several years. In this study, we describe the use of LifeCode to code all
      findings within a set of 500 cancer-related radiology reports against a test set
      in which all findings were manually tagged. The system was trained with 1400
      reports prior to running the test set. RESULTS: LifeCode had a recall of 84.5%
      and precision of 95.7% in the coding of cancer-related radiology report findings.
      CONCLUSION: Despite the use of a modest sized training set and minimal training
      iterations, when applied to cancer-related reports the system achieved recall and
      precision measures comparable to other reputable natural language processors in
      this domain.

PMID- 14728208
TI  - Cross-language MeSH indexing using morpho-semantic normalization.
AB  - We consider three alternative procedures for the automatic indexing of medical
      documents using MeSH thesaurus identifiers as target units (document
      descriptors). Rather than considering complete words as the starting point of the
      indexing procedure, we here propose morphologically plausible subwords as basic
      units from which MeSH terms are derived. We describe the morphological
      segmentation and normalization procedures, as well as the mappings from subwords
      to MeSH terms, and discuss results from an evaluation carried out on a German
      language corpus.

PMID- 14728209
TI  - Understanding search failures in consumer health information systems.
AB  - We examined queries that led to search failures on two National Library of
      Medicine Web-based consumer health sites, ClincialTrials.gov and MEDLINEplus. The
      purpose of the study was to analyze and categorize queries resulting that led to
      no results with the ultimate goal of developing interventions to assist users in
      recovering from those failures. We first analyzed over 2,700 queries, iteratively
      developing a coding scheme. We subsequently applied the codes to an additional
      set of 2,000 queries. We found that most of the queries were in scope, relevant
      to the system being searched, and did not exhibit so-called consumer language. As
      the final step, we developed a taxonomy based on whether the search failures were
      due primarily to content issues, to problems in query formulation, or to
      limitations of the search system. The results reported here have informed the
      further development of our own systems, and they may be helpful to others as they
      seek to improve consumer access to health information.

PMID- 14728211
TI  - Categorization of sentence types in medical abstracts.
AB  - This study evaluated the use of machine learning techniques in the classification
      of sentence type. 7253 structured abstracts and 204 unstructured abstracts of
      Randomized Controlled Trials from MedLINE were parsed into sentences and each
      sentence was labeled as one of four types (Introduction, Method, Result, or
      Conclusion). Support Vector Machine (SVM) and Linear Classifier models were
      generated and evaluated on cross-validated data. Treating sentences as a simple
      "bag of words", the SVM model had an average ROC area of 0.92. Adding a feature
      of relative sentence location improved performance markedly for some models and
      overall increasing the average ROC to 0.95. Linear classifier performance was
      significantly worse than the SVM in all datasets. Using the SVM model trained on
      structured abstracts to predict unstructured abstracts yielded performance
      similar to that of models trained with unstructured abstracts in 3 of the 4
      types. We conclude that classification of sentence type seems feasible within the
      domain of RCT's. Identification of sentence types may be helpful for providing
      context to end users or other text summarization techniques.

PMID- 14728210
TI  - Creating a virtual community of learning predicated on medical student learning
      styles.
AB  - To create a virtual community of learning within the Indiana University School of
      Medicine, learning tools were developed within ANGEL to meet the learning needs
      and habits of the medical students. METHODS: Determined by student feedback, the
      integration of digital audio recordings of class lectures into the course
      management content with several possible outputs was paramount. The other
      components included electronic enhancement of old exams and providing case-based
      tutorials within the ANGEL framework. RESULTS: Students are using the curriculum
      management system more. Faculty feel more secure about their intellectual
      property because of the authentication and security offered through the ANGEL
      system. The technology applications were comparatively easy to create and manage.
      The return on investment, particularly for the digital audio recording component,
      has been substantial. CONCLUSION: By considering student learning styles, extant
      curriculum management systems can be enhanced to facilitate student learning
      within an electronic environment.

PMID- 14728212
TI  - Expression array annotation using the BioMediator biological data integration
      system and the BioConductor analytic platform.
AB  - This paper presents the implementation of a model for expression array annotation
      (EAA) using the BioMediator biological data integration system along with
      BioConductor, an analytic tools platform. The model presented addresses the need
      for annotation sources identified during BioConductor inverted exclamation mark s
      development. Annotation provides us with well-curated genomic background
      knowledge for expression array analysis and interpretation. Annotation requests
      are constructed and posted to the query interface of the EAA package (the EAA
      model implemented as a component of BioConductor). The software enumerates all
      possible annotation paths for queries. These are then transformed to PQL queries
      and processed by BioMediator. Annotation entities returned from the EAA package
      answer the annotation request.

PMID- 14728213
TI  - Representing complexity in part-whole relationships within the Foundational Model
      of Anatomy.
AB  - The Foundational Model of Anatomy (FMA) is a frame-based ontology that represents
      declarative knowledge about the structural organization of the human body. Part
      whole relationships play a particularly important role in this representation. In
      order to assure that knowledge-based applications relying on the FMA as a
      resource can reason about anatomy, we have modified and enhanced currently
      available schemes of meronymic relationships. We have introduced and defined
      distinct partitions for decomposing anatomical structures and attributed the part
      relationships in order to eliminate ambiguity and enhance specificity in the
      richness of meronymic relationships within the FMA.

PMID- 14728214
TI  - Medical problem and document model for natural language understanding.
AB  - We are developing tools to help maintain a complete, accurate and timely problem
      list within a general purpose Electronic Medical Record system. As a part of this
      project, we have designed a system to automatically retrieve medical problems
      from free-text documents. Here we describe an information model based on XML
      (eXtensible Markup Language) and compliant with the CDA (Clinical Document
      Architecture). This model is used to ease the exchange of clinical data between
      the Natural Language Understanding application that retrieves potential problems
      from narrative document, and the problem list management application.

PMID- 14728215
TI  - Gene indexing: characterization and analysis of NLM's GeneRIFs.
AB  - We present an initial analysis of the National Library of Medicine's (NLM) Gene
      Indexing initiative. Gene Indexing occurs at the time of indexing for all 4600
      journals and over 500,000 articles added to PubMed/MEDLINE each year. Gene
      Indexing links articles about the basic biology of a gene or protein within eight
      model organisms to a specific record in the NLM's LocusLink database of gene
      products. The result is an entry called a Gene Reference Into Function (GeneRIF)
      within the LocusLink database. We analyzed the numbers of GeneRIFs produced in
      the first year of GeneRIF production. 27,645 GeneRIFs were produced, pertaining
      to 9126 loci over eight model organisms. 60% of these were associated with human
      genes and 27% with mouse genes. About 80% discuss genes with an established MeSH
      Heading or other MeSH term. We developed a prototype functional alerting system
      for researchers based on the GeneRIFs, and a strategy to find all of the
      literature related to genes. We conclude that the Gene Indexing initiative adds
      considerable value to the life sciences research community.

PMID- 14728216
TI  - Classifying instantaneous cognitive states from FMRI data.
AB  - We consider the problem of detecting the instantaneous cognitive state of a human
      subject based on their observed functional Magnetic Resonance Imaging (fMRI)
      data. Whereas fMRI has been widely used to determine average activation in
      different brain regions, our problem of automatically decoding instantaneous
      cognitive states has received little attention. This problem is relevant to
      diagnosing cognitive processes in neurologically normal and abnormal subjects. We
      describe a machine learning approach to this problem, and report on its
      successful use for discriminating cognitive states such as observing a picture
      versus reading a sentence, and reading a word about people versus reading a word
      about buildings.

PMID- 14728217
TI  - On-line information about cancer clinical trials: evaluating the Web sites of
      comprehensive cancer centers.
AB  - The objective of this study was to examine the information provided on
      comprehensive cancer centers' Web sites regarding clinical trials. Thirty-nine
      Web sites were visually inspected for four categories of variables: navigation to
      the clinical trial information, search functionality provided to the visitor,
      information content provided about trials, and the reading level of the
      information provided. Results indicated that for those Web sites that provided
      information about clinical trials, the content was often limited and trial
      descriptions were written at a college reading level. This study suggests that
      these Web sites are not yet adequately designed to serve as a successful aid for
      increased trial accrual. The design of future online clinical trial information
      should be guided by data from consumer health informatics research.

PMID- 14728218
TI  - Workflow management of HIS/RIS textual documents with PACS image studies for
      neuroradiology.
AB  - Reviewing brain tumor patients' complete medical record is a daunting task for
      any clinician. In current practice, the radiologist examines the most recent
      documents and then dictates an assessment of the patient's condition based on a
      review of the most current imaging study and compared with the most recent
      previous image study. Occasionally, the radiologist searches other clinical
      documents when more precise detail is needed. The purpose of this research is to
      develop effective methods to review all of the pertinent information in a patient
      medical record incorporating HIS (Hospital Information Systems), RIS (Radiology
      Information Systems) and PACS (Picture Archiving and Communications Systems)
      information in three distinct ways: filtering the document worklist for pertinent
      clinical data, identification of key clusters of clinical information, and an
      automatic hanging protocol that displays the MR images for optimal image
      comparison.

PMID- 14728219
TI  - Database-driven computerized antibiotic decision support: novel use of expert
      antibiotic susceptibility rules embedded in a pathogen-antibiotic logic matrix.
AB  - To better serve an antibiotic guidance program, we hypothesized that the
      relatively few antibiotic susceptibility measurements conducted in the
      microbiology laboratory could be extended to predict antibiotic susceptibilities
      for all antibiotics on the hospital formulary using expert infectious disease
      logic. With the assistance of infectious disease specialists, we developed these
      logic rules and then applied them to 26,196 unique patient culture specimens and
      the accompanying 334,131 antibiotic susceptibility measurements generating
      804,809 additional predicted bug-drug susceptibility data points. From the
      resulting data set, the antibiotic susceptibility profile for one pathogen,
      Streptococcus pneumoniae, is highlighted herein. We then incorporated the
      extended susceptibility profiles into a computerized antibiotic guidance program
      that matches current patients of interest with the positive cultures from past
      similar patients and calculates predicted effective antibiotic therapy. We
      conclude that this method successfully derives antibiotic predictions and merits
      further testing to evaluate its potential use in the hospital environment.

PMID- 14728220
TI  - Organisational culture matters for system integration in health care.
AB  - This paper illustrates the importance of organisational culture for Clinical
      Information Systems (CIS) integration. The study is based on data collected in
      intensive care units in the UK and Denmark. Data were collected using qualitative
      methods, i.e., observations, interviews and shadowing of health care providers,
      together with a questionnaire at each site. The data are analysed to extract
      salient variables for CIS integration, and it is shown that these variables can
      be separated into two categories that describe the 'Actual Usefulness' of the
      system and the 'Organisational Culture'. This model is then extended to show that
      CIS integration directly affects the work processes of the organisation, forming
      an iterative process of change as a CIS is introduced and integrated.

PMID- 14728221
TI  - A visual interface designed for novice users to find research patient cohorts in
      a large biomedical database.
AB  - One of the more difficult tasks of informatics is allowing for the navigation of
      complex databases. At Partners Healthcare Inc. we have developed an analytical
      database to allow for searching clinical data to obtain cohorts of patients for
      research studies. The characteristics of the patients within the cohorts must
      often comply with complex inclusion and exclusion criteria. The users of the
      database are research clinicians, often with no prior database experience. To
      assist these clinicians in finding their patient cohorts, we constructed a
      Querytool that they use directly to find their desired populations. In order to
      understand if the Querytool could indeed be used successfully by novice users, we
      analyzed the first 10 queries of 219 users. This analysis was able show that
      novice users are able to achieve excellent success using the Querytool

PMID- 14728222
TI  - A neuro-fuzzy approach to classification of ECG signals for ischemic heart
      disease diagnosis.
AB  - The paper focuses on the neuro-fuzzy classifier called Fuzzy-Gaussian Neural
      Network (FGNN) to recognize the ECG signals for Ischemic Heart Disease (IHD)
      diagnosis. The proposed ECG processing cascade has two main stages: (a) Feature
      extraction from the QRST zone of ECG signals using either the Principal Component
      Analysis (PCA) or the Discrete Cosine Transform (DCT); (b) Pattern classification
      for IHD diagnosis using the FGNN. We have performed the software implementation
      and have experimented the proposed neuro-fuzzy model for IHD diagnosis. We have
      used an ECG database of 40 subjects, where 20 subjects are IHD patients and the
      other 20 are normal ones. The best performance has been of 100% IHD recognition
      score. The result is exciting as much as we have used only one lead (V5) of ECG
      records as input data, while the current diagnosis approaches require the set of
      12 lead ECG signals!

PMID- 14728223
TI  - Weaning infants with respiratory syncytial virus from mechanical ventilation
      through a fuzzy-logic controller.
AB  - We have previously developed a fuzzy logic controller for weaning adults with
      chronic obstructive pulmonary disease using pressure support ventilation (PSV).
      We used the core of our fuzzy logic-based weaning platform and further developed
      parametrizable components for weaning newborns of differing body size and disease
      state. The controller was validated on neonates recovering from congenital heart
      disease (CHD) while receiving synchronous intermittent mandatory ventilation
      (SIMV). We wished to compare the efficacy of this controller versus the bedside
      weaning protocol in children with respiratory syncytial virus
      pneumonitis/bronchiolitis (RSV) in the pediatric intensive care unit (PICU). The
      fuzzy controller evaluated the "current" and "trend" weaning status of the
      newborn to quantitatively determine the change in the SIMV integrated ventilatory
      setting. For the "current" status it used heart rate (HR), respiratory rate (RR),
      tidal volume (VT) and oxygen saturation (SaO2), while for the "trend" status the
      differences of deltaRR/ deltat, deltaHR/ deltat, and deltaSaO2/ deltat recorded
      between two subsequent time points were utilized. The enumerated vital signs were
      fuzzified and then probability levels of occurrence were assigned. Individualized
      "golden" goals for SaO2 were set for each newborn. We retrospectively assessed
      the charts of 19 newborns, 113+/-128 days old, 5,546+/-2,321 gr body weight,
      weaning for 99+/-46 days, at 2-hour intervals. The SIMV levels proposed by the
      fuzzy controller were matched to those levels actually applied. In 60% of the
      time both values coincided. For the remaining 40%, the controller was more
      aggressive suggesting lower values of SIMV than the applied ones. The Area under
      the SIMV curves over time was 1,969+/-1,044 for the applied vs 1,886+/-978 for
      the suggested levels, respectively. The fuzzy controller adjusted for body size
      and disease-pattern can approximate the actual weaning course of newborns with
      RSV.

PMID- 14728224
TI  - Reference terminology for therapeutic goals: a new approach.
AB  - Participants at the Nursing Terminology Summit Conference 2002 developed proposed
      terminology models and information models for findings, goals, and outcomes and
      described the relationships among these concepts. At Vanderbilt University the
      author has dissected items in a controlled vocabulary of goals in accordance with
      the terminology model for findings. The concept-based dissections are linked to
      pre-coordinated phrases in a relational database, providing unambiguous
      definitions of clinical expressions and enabling concept-oriented searching of
      the terms database and of the goal achievement database.

PMID- 14728225
TI  - Approaches for guideline versioning using GLIF.
AB  - Computer-interpretable clinical guidelines (CIGs) aim to eliminate clinician
      errors, reduce practice variation, and promote best medical practices by
      delivering patient-specific advice during patient encounters. Clinical guidelines
      are being regularly updated and revised to handle expanding clinical knowledge.
      When revising CIGs, much effort can be saved by specifying changes among versions
      instead of encoding revised guidelines from scratch. A representation of
      differences between versions could focus the process of re-implementing CIGs in a
      clinical environment and help users understand and embrace changes. Guideline
      versioning has not been adequately dealt with by existing CIG formalisms. We
      present three approaches for CIG versioning. Focusing on one approach, we
      developed a versioning tool based on version 3 of the GuideLine Interchange
      Format (GLIF3), and used it to represent two guideline versions for management of
      community-acquired pneumonia (CAP) and the changes between them.

PMID- 14728226
TI  - Contextualizing heterogeneous data for integration and inference.
AB  - Systems that attempt to integrate and analyze data from multiple data sources are
      greatly aided by the addition of specific semantic and metadata "context" that
      explicitly describes what a data value means. In this paper, we describe a
      systematic approach to constructing models of data and their context. Our
      approach provides a generic "template" for constructing such models. For each
      data source, a developer creates a customized model by filling in the tem-plate
      with predefined attributes and value. This approach facilitates model
      construction and provides consistent syntax and semantics among models created
      with the template. Systems that can process the template structure and attribute
      values can reason about any model so described. We used the template to create a
      detailed knowledge base for syndromic surveillance data integration and analysis.
      The knowledge base provided support for data integration, translation, and
      analysis methods.

PMID- 14728227
TI  - Awareness-based scheduling in a home care clinical information system.
AB  - In home care, workers from different disciplines treat patients in their homes.
      However, workers who treat a shared patient are mobile and rarely see each other
      face-to-face, so it is difficult for them to maintain awareness of others'
      activities. In this paper, we discuss one aspect of these information limitations
      by considering how limited awareness of others' schedules influences work
      patterns in home care. We identify and discuss several problems that arise from
      incomplete information about others' schedules. We examine design approaches for
      supporting mutual awareness of others' schedules by presenting Mohoc, a point-of
      care clinical information system for workers in Saskatoon District Health, and
      the results of a 2(1/2)-month field trial we carried out with the system.

PMID- 14728228
TI  - Coordination challenges in operating-room management: an in-depth field study.
AB  - Dynamic settings possess complex information needs all requiring attention in
      order to be managed effectively. The following study describes the multi-faceted
      information exchanges essential for an operating room suite to be managed within
      the context of efficient, cost effective, safe practice. Through the combined use
      of observation, the Critical Incident Technique, and interviews, this study
      analyzed information issues that impact coordination. Results demonstrate how
      distributed team planning is inherent to the efficacy of the system, and discuss
      implications for information tools to support coordination within in a complex
      setting.

PMID- 14728229
TI  - A study of biomedical concept identification: MetaMap vs. people.
AB  - Although huge amounts of unstructured text are available as a rich source of
      biomedical knowledge, to process this unstructured knowledge requires tools that
      identify concepts from free-form text. MetaMap is one tool that system developers
      in biomedicine have commonly used for such a task, but few have studied how well
      it accomplishes this task in general. In this paper, we report on a study that
      compares MetaMap's performance against that of six people. Such studies are
      challenging because the task is inherently subjective and establishing consensus
      is difficult. Nonetheless, for those concepts that subjects generally agreed on,
      MetaMap was able to identify most concepts, if they were represented in the UMLS.
      However, MetaMap identified many other concepts that peo-ple did not. We also
      report on our analysis of the types of failures that MetaMap exhibited as well as
      trends in the way people chose to identify concepts.

PMID- 14728230
TI  - Web-based data and knowledge sharing between stroke units and general
      practitioners.
AB  - We describe a telemedicine application for emergency management in Stroke Units,
      where prompt decisions must be taken, often knowing neither the clinical history
      nor the stroke symptoms onset modality. We have designed and implemented an
      Information and Communication Technology architecture for the situation in which
      a general practitioner is called for a suspected stroke and provides for the
      admission to a Stroke Unit. By means of a palmtop and a wireless Internet
      connection, he can send to the Stroke Unit the demographic data, the list of the
      patient's problems, current and/or recent therapies, and a guideline-based stroke
      specific form with the objective examination results. In this way, the Stroke
      Unit team is alerted and informed before the patient arrival, and can manage the
      urgency at the best. The proposal involved 20 general practitioners and one
      Stroke Unit in the Lombardia Region, Italy.

PMID- 14728231
TI  - The use of computer telephony to provide interactive health information.
AB  - The use of information technology to provide health information to the public has
      grown at a rapid pace. Numerous sources of health care information within both
      the print and Internet media are now available. Yet, their availability raises
      concerns about the quality of the information provided and questions about which
      is the most effective method for transmitting health information to consumers. We
      present an interactive method of presenting high-quality health information that
      uses a new approach: an integration of the telephone and the computer also called
      computer telephony. Telephone-Linked Communication for Health Information (TLC
      HI) is a computer-based telecommunications system that functions as an educator
      to people in search of answers to health-related issues. To create TLC-HI, we
      converted validated print-based consumer information into computer-controlled
      conversational dialogues. We discuss the potential that the TLC-HI approach holds
      for improving the way health information is communicated.

PMID- 14728232
TI  - Challenges to physicians' use of a wireless alert pager.
AB  - Pagers, personal data assistants (PDAs) and other devices that have wireless
      connectivity are becoming a popular method for delivering patient related
      information to medical decision makers. Although medical informatics research has
      emphasized the design, and implementation of pagers as event notification
      mechanisms, researchers have not paid as much attention to how this technology
      impacts medical work. We present a case study of physicians in a Surgical
      Intensive Care Unit (SICU) using wireless alert pagers. The pagers provide a
      variety of alphanumeric clinical alert messages and are widely used by SICU
      physicians. However, the use of the pagers has created unanticipated challenges
      to the physicians' traditional work practices. These challenges include: (1)
      flattening of hierarchical workflows, (2) coping with information overload and
      missing context, and (3) lack of feedback. These challenges are tied to both the
      specific technical design of the system and the traditional structure of medical
      work.

PMID- 14728233
TI  - Integrating syndromic surveillance data across multiple locations: effects on
      outbreak detection performance.
AB  - Syndromic surveillance systems are being deployed widely to monitor for signals
      of covert bioterrorist attacks. Regional systems are being established through
      the integration of local surveillance data across multiple facilities. We studied
      how different methods of data integration affect outbreak detection performance.
      We used a simulation relying on a semi-synthetic dataset, introducing simulated
      outbreaks of different sizes into historical visit data from two hospitals. In
      one simulation, we introduced the synthetic outbreak evenly into both hospital
      datasets (aggregate model). In the second, the outbreak was introduced into only
      one or the other of the hospital datasets (local model). We found that the
      aggregate model had a higher sensitivity for detecting outbreaks that were evenly
      distributed between the hospitals. However, for outbreaks that were localized to
      one facility, maintaining individual models for each location proved to be
      better. Given the complementary benefits offered by both approaches, the results
      suggest building a hybrid system that includes both individual models for each
      location, and an aggregate model that combines all the data. We also discuss
      options for multi-level signal integration hierarchies.

PMID- 14728234
TI  - Semantic relations asserting the etiology of genetic diseases.
AB  - Considerable research is being directed at extracting molecular biology
      information from text. Particularly challenging in this regard is to identify
      relations between entities, such as protein-protein interactions or molecular
      pathways. In this paper we present a natural language processing method for
      extracting causal relations between genetic phenomena and diseases. After
      presenting the results of preliminary evaluation, we suggest the use of a
      graphical display application for viewing the semantic predications produced by
      the system.

PMID- 14728235
TI  - Designing a knowledge management system for distributed activities: a human
      centered approach.
AB  - In this study we use the principles of distributed cognition and the methodology
      of human-centered distributed information design to analyze a complex distributed
      human-computer system, identify its problems, and generate design requirements
      and implementation specifications of a replacement prototype for effective
      organizational memory and knowledge management. We argue that a distributed human
      computer information system has unique properties, structures and processes that
      are best described in the language of distributed cognition. Distributed
      cognition provides researchers a richer theoretical understanding of human
      computer interactions and enables re-searchers to capture the phenomenon that
      emerges in social interactions as well as the interactions between people and
      structures in their environment.

PMID- 14728236
TI  - Machine translation-supported cross-language information retrieval for a consumer
      health resource.
AB  - The U.S. National Institutes of Health, through its National Library of Medicine,
      developed ClinicalTrials.gov to provide the public with easy access to
      information on clinical trials on a wide range of conditions or diseases. Only
      English language information retrieval is currently supported. Given the growing
      number of Spanish speakers in the U.S. and their increasing use of the Web, we
      anticipate a significant increase in Spanish-speaking users. This study compares
      the effectiveness of two common cross-language information retrieval methods
      using machine translation, query translation versus document translation, using a
      subset of genuine user queries from ClinicalTrials.gov. Preliminary results
      conducted with the ClinicalTrials.gov search engine show that in our environment,
      query translation is statistically significantly better than document
      translation. We discuss possible reasons for this result and we conclude with
      suggestions for future work.

PMID- 14728237
TI  - Adequacy of representation of the National Drug File Reference Terminology
      Physiologic Effects reference hierarchy for commonly prescribed medications.
AB  - The National Drug File Reference Terminology contains a novel reference hierarchy
      to describe physiologic effects (PE) of drugs. The PE reference hierarchy
      contains 1697 concepts arranged into two broad categories; organ specific and
      generalized systemic effects. This investigation evaluated the appropriateness of
      the PE concepts for classifying a random selection of commonly prescribed
      medications. Ten physician reviewers classified the physiologic effects of ten
      drugs and rated the accuracy of the selected term. Inter reviewer agreement,
      overall confidence, and concept frequencies were assessed and were correlated
      with the complexity of the drug's known physiologic effects. In general,
      agreement between reviewers was fair to moderate (kappa 0.08-0.49). The
      physiologic effects modeled became more disperse with drugs having and inducing
      multiple physiologic processes. Complete modeling of all physiologic effects was
      limited by reviewers focusing on different physiologic processes. The reviewers
      were generally comfortable with the accuracy of the concepts selected. Overall,
      the PE reference hierarchy was useful for physician reviewers classifying the
      physiologic effects of drugs. Ongoing evolution of the PE reference hierarchy as
      it evolves should take into account the experiences of our reviewers.

PMID- 14728238
TI  - Cognitive evaluation of the predictors of use of computerized protocols by
      clinicians.
AB  - We describe a cognitive approach to evaluating the factors that motivate
      clinicians to use computerized protocols. Using Value-Expectancy theories we
      developed an open-ended interview to assess clinicians' beliefs and experiences
      about the use of computerized protocols. Using a qualitative methodology, 3
      reviewers independently identified key concepts raised by 13 interviewees. These
      concepts were aggregated and independently sorted into 39 categories. Then final
      categories were chosen by consensus. Analysis of the concepts showed consistency
      across clinician specialties of physicians, nurses and respiratory therapists.
      Inter-rater reliability calculated using Cohen's Kappa was 0.474. Identified
      constructs from Value-Expectancy and Intrinsic Motivation theories were: Work
      Importance, Perception of Situation, Role Relevance, Beliefs regarding Control,
      Beliefs regarding Normative Expectations, Beliefs regarding Self-Efficacy,
      Attitude, Habit, Environmental Support and Pre-Behavior. This model will form the
      basis for an instrument to assess the beliefs and expectations of clinical use
      regarding the use of computerized protocols.

PMID- 14728239
TI  - A data-driven approach for extracting "the most specific term" for ontology
      development.
AB  - We present a data-driven approach to extract the "most specific" terms relevant
      to an ontology of functioning, disability and health. The algorithm is a
      combination of statistical and linguistic approaches. The statistical filter is
      based on the frequency of the content words in a given text string; the
      linguistic heuristic is an extension of existing algorithms but goes beyond noun
      phrases and is formulated as a "complete syntactic node". Thus, it can be applied
      to any syntactic node of interest in the particular domain. Two test sets were
      marked by three experts. Test set 1 is a well-constructed text from pain
      abstracts; test set 2 is actual medical reports. Results are reported as recall,
      precision, F-score and rate of valid terms in false positives. A limitation of
      the current research is the relatively small test set.

PMID- 14728240
TI  - Extracting structured information from free text pathology reports.
AB  - We have developed a method that extracts structured information about specimens
      and their related findings in free-text surgical pathology reports. Our method
      uses regular expressions that drive a state-automaton on top of XSLT and Java.
      Text fragments identified are coded against the UMLS. This paper describes the
      technical approach and reports on a preliminary evaluation study, designed to
      guide further development. We found that of 275 reviewed reports, 91% were coded
      at least so that all specimens and their critical pathologic findings were
      represented in codes.

PMID- 14728242
TI  - Specifying design criteria for electronic medical record interface using
      cognitive framework.
AB  - As the healthcare industry transitions from paper to electronic medical records
      (EMRs), medical informatics researchers face the task of ensuring that the
      electronic presentation of the information remains usable and effective while
      capitalizing on the ability of EMRs to tailor information to different users. In
      our research, we focus on utilizing formal cognitive science methodology to guide
      the conversion of paper-based narrative discharge summaries to a more dynamic,
      structured electronic version. In this paper, we present the results of a
      cognitive analytic study (1) that determines a 'core' component in medical
      narratives and (2) that compares the use of structured and narrative texts by
      physicians with varying expertise. Specifically, we studied six psychiatrists at
      three levels of expertise- experts, intermediates, and novices. The subjects were
      given two clinical case scenarios with discharge summaries and asked to verbalize
      their thoughts as they read through the summaries. The interview transcripts were
      analyzed for recalls and inferences generated in the verbalization. Based on
      experts' verbalizations, the discharge summaries were organized into a more
      structured form and used in the interview of other subjects. Novice-level
      subjects had more recall with the structured than with the narrative format. More
      errors were also made in recall with the narrative than with the structured text.
      We discuss how these results are valuable in designing an EMR interface to reduce
      errors and to support users of different expertise.

PMID- 14728241
TI  - A distributed, collaborative, structuring model for a clinical-guideline digital
      library.
AB  - The Digital Electronic Guideline Library (DeGeL) is a Web-based framework and a
      set of distributed tools that facilitate gradual conversion of clinical
      guidelines from free text, through semi-structured text, to a fully structured,
      executable representation. Thus, guidelines exist in a hybrid, multiple-format
      representation The three formats support increasingly sophisticated computational
      tasks. The tools perform semantic markup, classification, search, and browsing,
      and support computational modules that we are developing, for run-time
      application and retrospective quality assessment. We describe the DeGeL
      architecture and its collaborative-authoring authorization model, which is based
      on (1) multiple medical-specialty authoring groups, each including a group
      manager who controls group authorizations, and (2) a hierarchical authorization
      model based on the different functions involved in the hybrid guideline
      specification process. We have implemented the core modules of the DeGeL
      architecture and demonstrated distributed markup and retrieval using the
      knowledge roles of two guidelines ontologies (Asbru and GEM). We are currently
      evaluating several of the DeGeL tools.

PMID- 14728243
TI  - A framework for classifying decision support systems.
AB  - BACKGROUND: Computer-based clinical decision support systems (CDSSs) vary greatly
      in design and function. A taxonomy for classifying CDSS structure and function
      would help efforts to describe and understand the variety of CDSSs in the
      literature, and to explore predictors of CDSS effectiveness and generalizability.
      OBJECTIVE: To define and test a taxonomy for characterizing the contextual,
      technical, and workflow features of CDSSs. METHODS: We retrieved and analyzed 150
      English language articles published between 1975 and 2002 that described computer
      systems designed to assist physicians and/or patients with clinical decision
      making. We identified aspects of CDSS structure or function and iterated our
      taxonomy until additional article reviews did not result in any new descriptors
      or taxonomic modifications. RESULTS: Our taxonomy comprises 95 descriptors along
      24 descriptive axes. These axes are in 5 categories: Context, Knowledge and Data
      Source, Decision Support, Information Delivery, and Workflow. The axes had an
      average of 3.96 coded choices each. 75% of the descriptors had an inter-rater
      agreement kappa of greater than 0.6. CONCLUSIONS: We have defined and tested a
      comprehensive, multi-faceted taxonomy of CDSSs that shows promising reliability
      for classifying CDSSs reported in the literature.

PMID- 14728244
TI  - A customizable MR brain imaging atlas of structure and function for decision
      support.
AB  - We present a MR brain atlas for structure and function (diffusion weighted
      images). The atlas is customizable for contrast and orientation to match the
      current patient images. In addition, the atlas also provides normative values of
      MR parameters (T1, T2 and ADC values). The atlas is designed on informatics
      principles to provide context sensitive decision support at the time of primary
      image interpretation. Additional support for diagnostic interpretation is
      provided by a list of expert created most relevant 'Image Finding Descriptors'
      that will serve as cues to the user. The architecture of the atlas module is
      integrated into the image workflow of a radiology department to provide support
      at the time of primary diagnosis.

PMID- 14728245
TI  - The ontology of the gene ontology.
AB  - The rapidly increasing wealth of genomic data has driven the development of tools
      to assist in the task of representing and processing information about genes,
      their products and their functions. One of the most important of these tools is
      the Gene Ontology (GO), which is being developed in tandem with work on a variety
      of bioinformatics databases. An examination of the structure of GO, however,
      reveals a number of problems, which we believe can be resolved by taking account
      of certain organizing principles drawn from philosophical ontology. We shall
      explore the results of applying such principles to GO with a view to improving
      GO's consistency and coherence and thus its future applicability in the automated
      processing of biological data.

PMID- 14728246
TI  - Effect of XML markup on retrieval of clinical documents.
AB  - OBJECTIVE: To determine the effect on clinical information retrieval of
      structuring typical clinical documents in XML, according to the general
      guidelines of Health Level Seven's Clinical Document Architecture. METHODS: One
      thousand clinical documents of eight frequently occurring types were deidentified
      and marked up in XML for access using a Web browser. Fifty information-seeking
      tasks were posed to subjects. The tasks were comprised of two typical clinical
      question types-individual patient results reporting and cohort identification. A
      control group of physician subjects could perform only free-text, keyword
      searching. The treatment group's interface permitted field-based searching of
      particular sections within each document. Differences in precision and other
      measures of search success across and between question types were investigated
      for statistical significance. RESULTS: No statistically significant differences
      were found between the control and treatment conditions in mean time elapsed or
      the mean number of records in the final result set. In fact, tasks performed in
      the treatment condition required a mean number of more steps in the search
      sequence to a degree that was statistically significant. Tasks performed in the
      treatment condition had a statistically significant lower rate of mean precision.
      There was no statistically significant difference between the means of relevance
      of the individual patient and cohort identification tasks. CONCLUSION: These
      findings are in line with Tange et al. who found that coarser granularity of
      clinical narrative gave better results. The results of this experiment also have
      implications for automatic text processing. Complex tag sets cannot ultimately
      resolve problems of unstandardized structure; the lack of existing structure
      within clinical documents is itself a significant limitation.

PMID- 14728247
TI  - A full XML-based approach to creating hypermedia learning modules in web-based
      environments: application to a pathology course.
AB  - Nowadays, web-based learning services are a key topic in the pedagogical and
      learning strategies of universities. While organisational and teaching
      requirements of the learning environment are being evaluated, technical
      specifications are emerging, enabling educators to build advanced "units of
      learning". Changes, however, take a long time and cost-effective solutions have
      to be found to involve our institutions in such actions. In this paper, we
      present a model of the components of a course. We detail the method followed to
      implement this model in hypermedia modules with a viewer that can be played on
      line or from a CD-ROM. The XML technology has been used to implement all the data
      structures and a client-side architecture has been designed to build a course
      viewer. Standards of description of content (such as Dublin Core and DocBook)
      have been integrated into the data structures. This tool has been populated with
      data from a pathology course and supports other medical contents. The choice of
      the architecture and the usefulness of the programming tools are discussed. The
      means of migrating towards a server-side application are presented.

PMID- 14728248
TI  - Web services-based access to local clinical trial databases: a standards
      initiative of the Association of American Cancer Institutes.
AB  - Electronic discovery of the clinical trials being performed at a specific
      research center is a challenging task, which presently requires manual review of
      the center's locally maintained databases or web pages of protocol listings. Near
      real-time automated discovery of available trials would increase the efficiency
      and effectiveness of clinical trial searching, and would facilitate the
      development of new services for information providers and consumers. Automated
      discovery efforts to date have been hindered by issues such as disparate database
      schemas, vocabularies, and insufficient standards for easy intersystem exchange
      of high-level data, but adequate infrastructure now exists that make possible the
      development of applications for near real-time automated discovery of trials.
      This paper describes the current state (design and implementation) of the Web
      Services Specification for Publication and Discovery of Clinical Trials as
      developed by the Technology Task Force of the Association of American Cancer
      Institutes. The paper then briefly discusses a prototype web service-based
      application that implements the specification. Directions for evolution of this
      specification are also discussed.

PMID- 14728249
TI  - Perception of quality and trustworthiness of Internet resources by personal
      health information seekers.
AB  - OBJECTIVES: This paper focuses on one dimension of personal health information
      seeking: perception of quality and trustworthiness of information sources.
      DESIGN: Intensive interviews were conducted using a conversational, unstructured,
      exploratory interview style. SETTING: Interviews were conducted at 3 publicly
      accessible library sites in Arizona, Hawaii and Nevada. PARTICIPANTS: Thirty
      eight non-experts were interviewed. RESULTS: Three separate and distinct methods
      used to identify credible health information resources were identified. Consumers
      may have strong opinions about what they mistrust; use fairly rigorous evaluation
      protocols; or filter information based on intuition or common sense, eye appeal
      or an authoritative sounding sponsor or title. CONCLUSIONS: Many people use a mix
      of rational and/or intuitive criteria to assess the health information they use.

PMID- 14728250
TI  - SKOLAR MD: a model for self-directed, in-context Continuing Medical Education.
AB  - SKOLAR has implemented a web-based CME program with which physicians can earn AMA
      Category 1 credit for self-directed learning. METHODS: Physicians researched
      their questions in SKOLAR and applied for CME. Physician auditors reviewed all
      requests across two phases of the project. A selection rule set was derived from
      phase one and used in phase two to flag a subset of requests for detailed review.
      The selection rule set is described. RESULTS: In phase one, SKOLAR received 1039
      CME applications. Applicants frequently found their answer (94%) and would apply
      it clinically (93%). A linear regression analysis comparing time awarded to time
      requested (capped at actual time spent) had R2=0.79. DISCUSSION: We believe that
      that this self-directed approach to CME is effective and an important complement
      to traditional CME programs. However, selective audit of self-directed CME
      requests is necessary to ensure validity of credits awarded.

PMID- 14728251
TI  - Adding a medical lexicon to an English Parser.
AB  - We present a heuristic method to map lexical (syntactic) information from one
      lexicon to another, and apply the technique to augment the lexicon of the Link
      Grammar Parser with an enormous medical vocabulary drawn from the Specialist
      lexicon developed by the National Library of Medicine. This paper presents and
      justifies the mapping method and addresses technical problems that have to be
      overcome. It illustrates the utility of the method with respect to a large corpus
      of emergency department notes.

PMID- 14728252
TI  - Dynamic XML-based exchange of relational data: application to the Human Brain
      Project.
AB  - This paper discusses an approach to exporting relational data in XML format for
      data exchange over the web. We describe the first real-world application of
      SilkRoute, a middleware program that dynamically converts existing relational
      data to a user-defined XML DTD. The application, called XBrain, wraps SilkRoute
      in a Java Server Pages framework, thus permitting a web-based XQuery interface to
      a legacy relational database. The application is demonstrated as a query
      interface to the University of Washington Brain Project's Language Map Experiment
      Management System, which is used to manage data about language organization in
      the brain.

PMID- 14728253
TI  - PAMFOnline: integrating EHealth with an electronic medical record system.
AB  - The Institute of Medicine stressed the need for continuous healing relationships,
      yet the delivery of health care has traditionally been confined to the physician
      office or hospital. We implemented an eHealth application tightly integrated with
      our electronic medical record system that provides patients with a convenient,
      continuously available communication channel to their physician's office.
      Patients can view summary data from their medical record, including the results
      of diagnostic tests, and request medical advice, prescription renewals,
      appointments, or updates to their demographic information. We have found that
      patients embrace this new communication channel and are using the service
      appropriately. Patients especially value electronic messaging with their
      physicians and timely access to their test results. While initially concerned
      about an increase in work, physicians have found that use of electronic messaging
      can be an efficient method for handling non-urgent communication with their
      patients. Online tools for patients, when integrated with an electronic medical
      record, can provide patients with better access to health information, improve
      patient satisfaction, and improve operational efficiency.

PMID- 14728254
TI  - User-centered development of a Web-based preschool vision screening tool.
AB  - Although amblyopia is most successfully treated when detected in early childhood,
      many preschool-aged children are not being screened. This project explored the
      delivery of Web-based vision screenings, integrated with patient education, to
      parents and children, aged 3 to 6 years. Through a user-centered design
      methodology involving requirements gathering, iterative prototype development,
      and usability testing, a highly usable screening Website was created.
      Interviewing and testing parents and children in the home were essential in
      gathering accurate data about environments where the tool would actually be used.
      Frequent iterations of designing, testing, and modifying the tool were useful in
      identifying and correcting usability problems. Usability goals were set early in
      the project, and in the final phase a satisfaction questionnaire was administered
      to participants. Twenty-one out of 22 final usability objectives were achieved
      and the feasibility of Web-based vision screening was demonstrated.

PMID- 14728255
TI  - Temporal consistency checking in clinical guidelines acquisition and execution:
      the GLARE's approach.
AB  - GLARE (GuideLine Acquisition, Representation and Execution) is a domain
      independent system for the acquisition, representation and execution of clinical
      guidelines. Temporal constraints play an important role within clinical
      guidelines (e.g. to specify therapies). The treatment of such constraints is one
      of the distinguishing features of GLARE. During acquisition, GLARE supports (i)
      the representation and (ii) the check of the consistency of the temporal
      constraints. Moreover, it (iii) automatically checks that the times of execution
      of specific actions respect the general temporal constraints described in the
      guideline. Such a treatment of temporal constraints involves the extension of
      various Artificial Intelligence techniques.

PMID- 14728256
TI  - Emergency Department data for bioterrorism surveillance: electronic data
      availability, timeliness, sources and standards.
AB  - Emergency Department (ED) data are a key component of bioterrorism surveillance
      systems. Little research has been done to examine differences in ED data capture
      and entry across hospitals, regions and states. The purpose of this study was to
      describe the current state of ED data for use in bioterrorism surveillance in 2
      regions of the country. We found that chief complaint (CC) data are available
      electronically in 54% of the North Carolina EDs surveyed, and in 100% of the
      Seattle area EDs. Over half of all EDs reported that CCs are recorded in free
      text form. Though all EDs have electronic diagnosis data, less than half report
      that diagnoses are coded within 24 hours of the ED visit.

PMID- 14728258
TI  - Exploring medical expressions used by consumers and the media: an emerging view
      of consumer health vocabularies.
AB  - Healthcare consumers often have difficulty expressing and understanding medical
      concepts. The goal of this study is to identify and characterize medical
      expressions or "terms" (linguistic forms and associated concepts) used by
      consumers and health mediators. In particular, these terms were characterized
      according to the degree to which they mapped to professional medical
      vocabularies. Lay participants identified approximately 100,000 term tokens from
      online discussion forum postings and print media articles. Of the over 81,000
      extracted term tokens reviewed, more than 75% were mapped as synonyms or quasi
      synonyms to the Unified Medical Language System (UMLS) Metathesaurus. While 80%
      conceptual overlap was found between closely mapped lay (consumer and mediator)
      and technical (professional) medical terms, about half of these overlapping
      concepts contained lay forms different from technical forms. This study raises
      questions about the nature of consumer health vocabularies that we believe have
      theoretical and practical implications for bridging the medical vocabulary gap
      between consumers and professionals.

PMID- 14728257
TI  - An approach to the anatomical correlation of species through the Foundational
      Model of Anatomy.
AB  - The increasing need for extrapolating information from one species to another has
      been highlighted by contemporary research in bioinformatics, genomics,
      proteomics, and animal models of human disease, as well as other fields. We
      propose an approach to correlating the anatomy of Homo sapiens with selected
      species, using the Foundational Model of Anatomy (FMA) as a framework, and graph
      matching as a method, for determining similarities and differences in the nodes
      and relationships (edges) defined by the attributed graph of the FMA. We
      illustrate our approach by comparing anatomical structures of mouse and human
      that present prototypical mapping problems.

PMID- 14728259
TI  - The structure of guideline recommendations: a synthesis.
AB  - We propose that recommendations in a clinical guideline can be structured either
      as collections of decisions that are to be applied in specific situations or as
      processes that specify activities that take place over time. We formalize them as
      "recommendation sets" consisting of either Activity Graphs that represent
      guideline-directed processes or Decision Maps that represent atemporal
      recommendations or recommendations involving decisions made at one time point. We
      model guideline processes as specializations of workflow processes and provide
      possible computational models for decision maps. We evaluate the proposed
      formalism by showing how various guideline-modeling methodologies, including
      GLIF, EON, PRODIGY3, and Medical Logic Modules can be mapped into the proposed
      structures. The generality of the formalism makes it a candidate for
      standardizing the structure of recommendations for computer-interpretable
      guidelines.

PMID- 14728260
TI  - The retina as a neuromimetic model to extract data in noisy images : application
      to detection of microcalcification clusters in mammography.
AB  - The nervous system is a powerful information processing machine, especially for
      vision. Neuromimetic methods try to extract some of the most powerful strategies
      of the neural system to apply them to help to solve delicate engineering
      problems. We developed such a method to extract images hidden into noisy
      background. This method mimics one characteristic of the retina which is a sensor
      that automatically adapts to the image characteristics and realizes outlines
      extraction and adaptative filtering, based on its network properties. We applied
      this method to detect automatically the clusters of microcalcifications in
      mammographies. Results were tested using the standardized data set DDSM, designed
      to test the automatic detection methods. We show that our "retina" can extract
      most of the microcalcifications that can be grouped together into clusters.

PMID- 14728261
TI  - Detecting adverse drug events in discharge summaries using variations on the
      simple Bayes model.
AB  - Detection and prevention of adverse events and, in particular, adverse drug
      events (ADEs), is an important problem in health care today. We describe the
      implementation and evaluation of four variations on the simple Bayes model for
      identifying ADE-related discharge summaries. Our results show that these
      probabilistic techniques achieve an ROC curve area of up to 0.77 in correctly
      determining which patient cases should be assigned an ADE-related ICD-9-CM code.
      These results suggest a potential for these techniques to contribute to the
      development of an automated system that helps identify ADEs, as a step toward
      further understanding and preventing them.

PMID- 14728262
TI  - GESDOR - a generic execution model for sharing of computer-interpretable clinical
      practice guidelines.
AB  - We developed the Guideline Execution by Semantic Decomposition of Representation
      (GESDOR) model to share guidelines encoded in different formats at the execution
      level. For this purpose, we extracted a set of generalized guideline execution
      tasks from the existing guideline representation models. We then created the
      mappings between specific guideline representation models and the set of the
      common guideline execution tasks. Finally, we developed a generic task-scheduling
      model to harmonize the existing approaches to guideline task scheduling. The
      evaluation has shown that the GESDOR model can be used for the effective
      execution of guidelines encoded in different formats, and thus realizes guideline
      sharing at the execution level.

PMID- 14728263
TI  - An applied evaluation of SNOMED CT as a clinical vocabulary for the computerized
      diagnosis and problem list.
AB  - The use of a standardized controlled terminology allows diverse systems and
      applications throughout the enterprise to translate data. In developing a
      customized enterprise-wide vocabulary for clinical terminology, we implemented
      SNOMED CT as a base vocabulary, while facilitating the addition of site-specific
      clinical terms or concepts not represented in SNOMED CT. In this paper, we
      evaluate the breadth of SNOMED CT terms and concepts for the coding of diagnosis
      and problem lists by clinicians within a computerized physician order entry
      (CPOE) system. Clinicians selected diagnosis and problem list terms from a
      lexicon based on SNOMED CT, submitting requests for clinical terms that were not
      found in the controlled vocabulary. For each "missing" term, we assigned one of
      four mapping types, representing the relationship of this new terminology entry
      to the SNOMED CT reference terminology. Our results show that the majority of
      diagnosis/problem list terms (88.4%) were found in SNOMED CT. Of the 145 missing
      terms, only 20 represented significant concepts missing from SNOMED CT, resulting
      in concept coverage of 98.5%. Our results show that SNOMED CT is a relatively
      complete standardized terminology on which to base a vocabulary for the clinical
      problem list.

PMID- 14728264
TI  - Ambiguity of human gene symbols in LocusLink and MEDLINE: creating an inventory
      and a disambiguation test collection.
AB  - Genes are discovered almost on a daily basis and new names have to be found.
      Although there are guidelines for gene nomenclature, the naming process is highly
      creative. Human genes are often named with a gene symbol and a longer, more
      descriptive term; the short form is very often an abbreviation of the long form.
      Abbreviations in biomedical language are highly ambiguous, i.e., one gene symbol
      often refers to more than one gene. Using an existing abbreviation expansion
      algorithm,we explore MEDLINE for the use of human gene symbols derived from
      LocusLink. It turns out that just over 40% of these symbols occur in MEDLINE,
      however, many of these occurrences are not related to genes. Along the process of
      making an inventory, a disambiguation test collection is constructed
      automatically.

PMID- 14728266
TI  - The dimensions of indexing.
AB  - Indexing of documents is an important strategy intended to make the literature
      more readily available to the user. Here we describe several dimensions of
      indexing that are important if indexing is to be optimal. These dimensions are
      coverage, predictability, and transparency. MeSH terms and text words are
      compared in MEDLINE in regard to these dimensions. Part of our analysis consists
      in applying AdaBoost with decisions trees as the weak learners to estimate how
      reliably index terms are being assigned and how complex the criteria are by which
      they are being assigned. Our conclusions are that MeSH terms are more predictable
      and more transparent than text words.

PMID- 14728265
TI  - Clinicians' and patients' experiences and satisfaction with unscheduled,
      nighttime, Internet-based video conferencing for assessing acute medical problems
      in a nursing facility.
AB  - Videoconferencing between patients and their physicians can increase patients'
      access to healthcare. Unscheduled videoconferencing can benefit patients with
      acute medical problems but has not been studied extensively. We conducted a
      clinical trial of unscheduled, nighttime videoconferencing in a nursing home,
      where on-call physicians usually provide care by telephone from remote locations.
      Although most calls for medical problems did not lead to videoconferencing,
      physicians and nursing-home residents were satisfied with videoconferencing when
      it did occur, and physicians reported that making medical decisions was easier
      with videoconferencing. Videoconferencing was most often conducted to assess
      residents with changes in mental status, abnormal laboratory values, or falls.
      Physicians often lacked immediate access to videoconferencing equipment when
      medical problems with residents occurred. This application could benefit from
      improved access and portability of equipment.

PMID- 14728267
TI  - Developing optimal search strategies for detecting clinically sound causation
      studies in MEDLINE.
AB  - BACKGROUND: Clinical end users of MEDLINE must be able to retrieve articles that
      are both scientifically sound and directly relevant to clinical practice. The use
      of methodologic search filters has been advocated to improve the accuracy of
      searching for such studies. These filters are available for the literature on
      therapy and diagnosis, but strategies for the literature on causation have been
      less well studied. OBJECTIVE: To determine the retrieval characteristics of
      methodologic terms in MEDLINE for identifying methodologically sound studies on
      causation. DESIGN: Comparison of methodologic search terms and phrases for the
      retrieval of citations in MEDLINE with a manual hand search of the literature
      (the gold standard) for 162 core health care journals. METHODS: 6 trained,
      experienced research assistants read all issues of 162 journals for the
      publishing year 2000. Each article was rated using purpose and quality indicators
      and categorized into clinically relevant original studies, review articles,
      general papers, or case reports. The original and review articles were then
      categorized as 'pass' or 'fail' for methodologic rigor in the areas of
      therapy/quality improvement, diagnosis, prognosis, causation, economics, clinical
      prediction, and review articles. Search strategies were developed for all
      categories including causation. MAIN OUTCOME MEASURES: Sensitivity, specificity,
      precision, and accuracy of the search strategies. RESULTS: 12% of studies
      classified as causation met basic criteria for scientific merit for testing
      clinical applications. Combinations of terms reached peak sensitivities of 93%.
      Compared with the best single term, multiple terms increased sensitivity for
      sound studies by 15.5% (absolute increase), but with some loss of specificity
      when sensitivity was maximized. Combining terms to optimize sensitivity and
      specificity achieved sensitivities and specificities both above 80%. CONCLUSION:
      The retrieval of causation studies cited in MEDLINE can be substantially enhanced
      by selected combinations of indexing terms and textwords.

PMID- 14728268
TI  - Web-based physician order entry: an open source solution with broad physician
      involvement.
AB  - Computerized physician order entry (CPOE) is a disruptive technology but holds
      great promise for reducing medical errors, improving workflow and in the long
      run, producing cost-savings. However, many studies have reported significant
      physician resistance to implementing CPOE. In this manuscript we present a two
      prong strategy for quick implementation of CPOE: 1) a web-based deployment tool
      using an open source, secure environment that allows rapid development and
      deployment of content, and 2) the development of a large set of disease specific
      order sets and knowledge bases based on established vocabulary standards such as
      LOINC and SNOMED CT by teams of multidisciplinary content experts at the
      departmental level. The order sets can be viewed, edited and signed through a
      standard browser interface. This paper presents the conceptual framework and
      implementation requirements for such an endeavor.

PMID- 14728269
TI  - Developing optimal search strategies for detecting sound clinical prediction
      studies in MEDLINE.
AB  - BACKGROUND: The gaining interest in the use of clinical prediction guides as an
      aid for helping clinicians make effective front-line decisions, together with the
      increasing emphasis on evidence-based practice, underscores the need for accurate
      identification of sound clinical prediction studies. Despite the growing use of
      clinical prediction guides, little work has been done on identifying optimal
      literature search filters for retrieving these types of studies. The current
      study extends our earlier work, on developing optimal search strategies, to
      include clinical prediction guides. OBJECTIVE: To develop optimal search
      strategies for detecting methodologically sound clinical prediction studies in
      MEDLINE in the publishing year 2000. DESIGN: Comparison of the retrieval
      performance of methodologic search strategies in MEDLINE with a manual review
      ("gold standard") of each article for each issue of 162 core health care journals
      for the year 2000. METHODS: 6 experienced research assistants who had been
      trained and intensively calibrated reviewed all issues of 162 journals for the
      publishing year 2000. Each article was classified for format, interest, purpose,
      and methodologic rigor. Search strategies were developed for all purpose
      categories, including studies of clinical prediction guides. MAIN OUTCOME
      MEASURES: The sensitivity (recall), specificity, precision, and accuracy of
      single and combinations of search terms. RESULTS: 39% of original studies
      classified as a clinical prediction guide were methodologically sound.
      Combinations of terms reached peak sensitivities of 95%. Compared with the best
      single term, a three-term strategy increased sensitivity for sound studies by 17%
      (absolute increase), but with some loss of specificity when sensitivity was
      maximized. When search terms were combined to optimize sensitivity and
      specificity, these values reached or were close to 90%. CONCLUSION: Several
      search strategies can enhance the retrieval of sound clinical prediction studies.

PMID- 14728270
TI  - A computer-based microarray experiment design-system for gene-regulation pathway
      discovery.
AB  - This paper reports the methods and evaluation of a computer-based system that
      recommends microarray experimental design for biologists - causal discovery in
      Gene Expression data using Expected Value of Experimentation (GEEVE). The GEEVE
      system uses causal Bayesian networks and generates a decision tree for
      recommendations. To evaluate the GEEVE system, we first built an expression
      simulation model based on a gene regulation model assessed by an expert
      biologist. Using the simulation model, we conducted a controlled study that
      involved 10 biologists, some of whom used GEEVE and some of whom did not. The
      results show that biologists who used GEEVE reached correct causal assessments
      about gene regulation more often than did those biologists who did not use GEEVE.

PMID- 14728271
TI  - Realization of real-time clinical data integration using advanced database
      technology.
AB  - As information & communication technologies have advanced, interest in mobile
      health care systems has grown. In order to obtain information seamlessly from
      distributed and fragmented clinical data from heterogeneous institutions, we need
      solutions that integrate data. In this article, we introduce a method for
      information integration based on real-time message communication using trigger
      and advanced database technologies. Messages were devised to conform to HL7, a
      standard for electronic data exchange in healthcare environments. The HL7 based
      system provides us with an integrated environment in which we are able to manage
      the complexities of medical data. We developed this message communication
      interface to generate and parse HL7 messages automatically from the database
      point of view. We discuss how easily real time data exchange is performed in the
      clinical information system, given the requirement for minimum loading of the
      database system.

PMID- 14728272
TI  - Evaluation of web accessibility of consumer health information websites.
AB  - The objectives of the study are to construct a comprehensive framework for web
      accessibility evaluation, to evaluate the current status of web accessibility of
      consumer health information websites and to investigate the relationship between
      web accessibility and property of the websites. We selected 108 consumer health
      information websites from the directory service of a Web search engine. We used
      Web accessibility specifications to construct a framework for the measurement of
      Web Accessibility Barriers (WAB) of website. We found that none of the websites
      is completely accessible to people with disabilities, but governmental and
      educational health information websites exhibit better performance on web
      accessibility than other categories of websites. We also found that the
      correlation between the WAB score and the popularity of a website is
      statistically significant.

PMID- 14728273
TI  - Detection of outbreaks from time series data using wavelet transform.
AB  - In this paper, we developed a new approach to detection of disease outbreaks
      based on wavelet transform. It is capable of dealing with two problems found in
      real-world time series data, namely, negative singularity and long-term trends,
      which may degrade the performance of current approaches to outbreak detection. To
      test this approach, we introduced artificail disease outbreaks and negative
      singularities into a real world dataset and applied it and two other algorithms
      autoregressive (AR) and Multi-resolution Wavelet Auto-regressive (MWAR) - to this
      dataset. We compared the performance of these algorithms in terms of sensitivity,
      specificity and timeliness. The results showed that our approach had similar
      sensitivity and specificity and slightly better timeliness compared to the other
      two algorithms. When we introduced negative singularities, its performance did
      not degrade as much as the other two algorithms' performance. We conclude that
      our approach to detection, when compared to traditional approaches, may not be as
      susceptible to degradation of performance caused by negative singularities.

PMID- 14728274
TI  - Aligning representations of anatomy using lexical and structural methods.
AB  - OBJECTIVE: The objective of this experiment is to develop methods for aligning
      two representations of anatomy (the Foundational Model of Anatomy and GALEN) at
      the lexical and structural level. METHODS: The alignment consists of the
      following four steps: 1)acquiring terms, 2) identifying anchors (i.e., shared
      concepts) lexically, 3) acquiring explicit and implicit semantic relations, and
      4) identifying anchors structurally. RESULTS: 2,353 anchors were identified by
      lexical methods, of which 91% were supported by structural evidence. No evidence
      was found for 7.5%of the anchors and 1.5% received negative evidence. DISCUSSION:
      The importance of taking advantage of implicit domain knowledge acquired through
      complementation,augmentation, and inference is discussed.

PMID- 14728275
TI  - Automated knowledge extraction for decision model construction: a data mining
      approach.
AB  - Combinations of Medical Subject Headings (MeSH) and Subheadings in MEDLINE
      citations may be used to infer relationships among medical concepts. To
      facilitate clinical decision model construction, we propose an approach to
      automatically extract semantic relations among medical terms from MEDLINE
      citations. We use the Apriori association rule mining algorithm to generate the
      co-occurrences of medical concepts, which are then filtered through a set of
      predefined semantic templates to instantiate useful relations. From such semantic
      relations, decision elements and possible relationships among them may be derived
      for clinical decision model construction. To evaluate the proposed method, we
      have conducted a case study in colorectal cancer management; preliminary results
      have shown that useful causal relations and decision alternatives can be
      extracted.

PMID- 14728276
TI  - IndexFinder: a method of extracting key concepts from clinical texts for
      indexing.
AB  - Extracting key concepts from clinical texts for indexing is an important task in
      implementing a medical digital library. Several methods are proposed for mapping
      free text into standard terms defined by the Unified Medical Language System
      (UMLS). For example, natural language processing techniques are used to map
      identified noun phrases into concepts. They are, however, not appropriate for
      real time applications. Therefore, in this paper, we present a new algorithm for
      generating all valid UMLS concepts by permuting the set of words in the input
      text and then filtering out the irrelevant concepts via syntactic and semantic
      filtering. We have implemented the algorithm as a web-based service that provides
      a search interface for researchers and computer programs. Our preliminary
      experiment shows that the algorithm is effective at discovering relevant UMLS
      concepts while achieving a throughput of 43K bytes of text per second. The tool
      can extract key concepts from clinical texts for indexing.

PMID- 14728277
TI  - Corpus-based associations provide additional morphological variants to medical
      terminologies.
AB  - Knowledge of morphologically derived words, as provided for medical English by
      the UMLS Specialist Lexicon, is useful to detect term variants for automated
      coding and indexing. For most other languages though, no comparable morphological
      knowledge base is available. We therefore endeavored to design general methods to
      help collect such knowledge for a given language. We propose here a method for
      discovering derived words in text corpora and apply it to a French medical
      corpus. To evaluate this method, we study its ability to suggest derived
      adjectives for 2,297 nouns found in the SNOMED nomenclature, which itself
      specifies adjectival equivalents for some of its terms. 74% of the proposed
      adjectives are judged correct (precision) and cover 16% of these nouns (recall),
      a larger amount than what SNOMED already specifies. Furthermore, the corpus
      suggests additional adjectives which can increase SNOMED's by 76%. We conclude
      that such a method can help speed up the construction of a morphological
      knowledge base which can increase the number of term variants in an existing
      controlled vocabulary.

PMID- 14728278
TI  - The Visible Human data sets (VHD) and Insight Toolkit (ITk): experiments in open
      source software.
AB  - From its inception in 1989, the Visible Human Project was designed as an
      experiment in open source software. In 1994 and 1995 the male and female Visible
      Human data sets were released by the National Library of Medicine (NLM) as open
      source data sets. In 2002 the NLM released the first version of the Insight
      Toolkit (ITk) as open source software.

PMID- 14728279
TI  - Assessment strategies: how patients cope with the diverse quality levels of
      websites when searching for health information.
AB  - The quality of online medical information available for patients has long been a
      concern of health care professionals. [1-4] Although initiatives exist for
      patients to use when searching for information, there is the concern that these
      initiatives are either ineffective or even counter-productive. [5-6] Another
      criticism is that initiatives do not sufficiently achieve their respective goals.
      [7-8] It is important to consider that many initiatives have been designed with
      patients in mind, but not with patients involved. Various portals, seals, rating
      systems, ethical codes, etc., exist ostensibly for patients, but arose largely
      without concrete input from real patients-as-end-users. Literature addressing
      usability on the basis of studies assessing real patients' searching behaviors
      appeared only in 2002. [9-11] The conclusions from these studies, while
      insightful, reflect the need for ongoing research into the daily practices of
      patients searching for web-based health care information. This poster highlights
      the first results of a systematic ethnographic study (interviews and shadow
      searching carried out between November, 2001 and August, 2003) to determine how
      patients approach health care information when searching on the internet and
      illustrates the different strategies that patients use to assess the health
      information they encounter on the web.

PMID- 14728280
TI  - Proposed classification of cells in the Foundational Model of Anatomy.
AB  - A logical and principled representation of cell types and their component parts
      could serve as a framework for correlating the various ontologies that are
      emerging in bioinformatics with a focus on cells and subcellular biological
      entities. In order to address this need we have extended the Foundational Model
      of Anatomy (FMA)1,2 from macroscopic to cellular and subcellular anatomical
      entities. The poster will provide a live demonstration of this implementation.

PMID- 14728281
TI  - Modeling and simulation role in designing a Teleradiology system.
AB  - In designing complex systems, Engineers, Developers and Systems Architects always
      have to make quantitative assumptions in order to satisfy anticipated loads and
      expectations of the final product. Many questions are asked before any complex
      system design that relate to systems performance, infrastructure and components
      configuration, behavior prediction and bottlenecks fixes. All these questions can
      be answered using modeling and simulation tools that allow engineers to predict
      systems behaviors in different settings and optimize systems in production by
      identifying bottlenecks and flaws in the infrastructure or workflow.

PMID- 14728282
TI  - Controlled health thesaurus for the CDC web redesign project.
AB  - A considerable number of robust vocabularies and thesauri have been developed for
      the healthcare and biomedical domain. No single vocabulary, however; provides
      complete coverage of the information needs from a public health perspective. The
      results of an investigation of vocabulary sources for the development of a
      comprehensive controlled vocabulary for the public health domain at the Centers
      for Disease Control and Prevention (CDC) is presented.

PMID- 14728283
TI  - Usability of online health information for people with disabilities.
AB  - Current issues around the usability of online health information for people with
      disabilities are to be presented and discussed. This includes a review of the
      current literature relevant to this area, a review of the current methodology for
      assessing Web usability, and a proposed model for addressing these issues to
      increase the access to online health information by people with disabilities, in
      particular for those with cognitive impairments. Available preliminary data will
      also be presented.

PMID- 14728284
TI  - Comparison of methods for evaluation of medical terminological systems.
AB  - The importance of terminological systems (TS) for the medical domain is widely
      recognized. The usability of such a system depends primarily on its content. We
      have designed four methods to evaluate the content of TS and applied them in a
      case study

PMID- 14728285
TI  - Handheld computer application for time-motion studies in the emergency
      department.
AB  - Urban academic emergency departments face significant challenges of increasing
      patient volumes and sicker patients. Better understanding of the timing and
      interactions between provider activities may assist in efforts directed toward
      improving patient-care processes to decrease length of stay. Rapidly chang-ing
      and overlapping activities in the emergency department make time-motion study
      difficult. This poster describes a handheld computer application that enables
      synchronized capture of task description and times across multiple patient care
      providers in the emergency department.

PMID- 14728286
TI  - Validation of automated event triggers using laboratory values related to two
      problem-prone drugs.
AB  - We used computerized alerts to identify patients with laboratory values that
      could be related to medication errors associated with digoxin and warfarin. Over
      a six-week period at two inpatient facilities, we generated 62 laboratory-based
      alerts for warfarin, and 66 for digoxin. The positive predictive value for these
      alerts representing a preventable event was 71% and 57% for warfarin and digoxin,
      respectively.

PMID- 14728287
TI  - IMPACT4: a framework for rapid, modular construction of web-based patient
      decision support systems and preference measurement tools.
AB  - To support the rapid creation of software systems that provide patients with
      decision support and measure patients' preferences, we have develop a framework
      called iMPACT4. The framework, which combines XML and Flash, has rich client-side
      state navigation control capabilities, reusable components, cross-platform
      compatibility, and facilitated access for persons with disabilities. It has many
      of the advanced navigation capabilities of complex server controlled web software
      while retaining an architecture that allows automated generation of web sites
      similar to our previous software system iMPACT3.

PMID- 14728288
TI  - Pharmacokinetic mapping of breast tumors: a new statistical analysis technique
      for dynamic magnetic resonance imaging.
AB  - Breast cancer is the most common malignancy among women, constituting a major
      health problem. Different MRI techniques have been investigated in the past in
      order to improve the detection and diagnosis of breast tumors. One such technique
      is the dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE
      MRI), using diffusible CM (contrast media), such as Gd-DTPA. Here we employ a two
      compartment CM kinetics model (blood plasma and surrounding interstitial space
      being the two compartments), where the exchange of contrast agent between these
      compartments is bidirectionally linear. In this study we use images from 29
      suspected breast carcinoma patients who underwent whole breast DCE-MRI. Each of
      these studies has 64 coronal sections of the whole breast, taken at 6 or 7 time
      points (the sampling period being about 2 minutes). Subsequent histo-pathological
      analysis of these patients reveal: 22 intraductal carcinomas (IDC), 3
      intralobular carcinomas (ILC), 2 ductal carcinomas in-situ (DCIS) and 3 benign
      tumors.

PMID- 14728289
TI  - Information needs of residents during inpatient and outpatient rotations:
      identifying effective personal digital assistant applications.
AB  - Last year, we reported (2002 AMIA Proceedings, p 971) on how medical school
      residents report on their use of personal digital assistants (PDA) or hand held
      devices. We first surveyed 88 residents in six residency programs representing
      both generalist and specialist practices (Family Medicine, Internal Medicine,
      Neurology, Pediatrics, Radiology, and Surgery. Following our survey, we contacted
      some of these same residents for follow-up advantages and disadvantages of
      specific software applications, and what information residents would like to have
      on their PDAs. Our survey and interview results included several specific
      advantages and disadvantages of PDA usage by residents. Advantages included: (1)
      many residents readily adapted the personal organizers (calendars. address books,
      to-do lists) to help keep track of their clinical tasks, and keeping in touch
      with patients, (2) commercial medical references (such as ePocrates) are used
      most by the surveyed residents to answer immediate medical questions. Perceived
      drawbacks include: (1) calculators and patient trackers that were not clearly
      able to be tailored to residents' needs, e.g., to limit and modify types of
      calculations to just those actually used, (2) physical size (both too small a
      display size, and too bulky overall), and (3) several residents mentioned a
      concern of becoming too dependent on one source of information, a source that was
      viewed as being too easy to lose or break. Three broad patterns emerged. First,
      residents in all seven of our surveyed practices use PDAs and most surveyed
      residents use them on a daily basis; we conclude that PDAs are being widely used
      across the spectrum of generalist to specialty practices, regardless of whether a
      residency program specifically encourages PDA usage. Second, security and HIPAA
      compliance issues need to be addressed, in part by resident education about
      archiving PDA files. Lastly, PDAs may become even more widely used if clinical
      data specific to an individual resident can easily and securely be maintained on
      PDAs. Design of Current Studies Our current study builds on the above perceived
      needs: we will follow residents during portions of a clinical day. Preliminary
      observations in three clinical areas (Medical Intensive Care Unit (MICU), General
      Medicine Outpatient, and Family Medicine Outpatient) confirm the conclusions of
      our previous study. PDAs are used for: (1) medical references (e.g., five minute
      clinical consult, Infotriever) (2) pharmaceutical information (such as
      ePocrates), and (3) professional organization (calendar, address book). Our
      intention in this new study is to identify the overall flow of information and
      how PDAs might improve the information flow in clinical settings. We choose to
      observe residents in both inpatient and outpatient clinics. We anticipate that
      PDAs will have different uses in these two settings; preliminary observations in
      one outpatient clinic (Family Medicine) suggests that PDAs are used during the
      doctor - patient interaction, specifically to suggest the importance of smoking
      cessation. Preliminary observations in an inpatient clinical setting (the MICU)
      suggest that PDAs are primarily used outside of patient rooms, e.g. to make
      medical calculations and to obtain diagnostic procedures. We plan to observe
      residents during various parts of their days in order to develop a detailed
      understanding of what information sources (e.g., consultations, computer reports,
      paper charts) are available at different times and which sources are frequently
      used. This information will help us develop a pocket-sized, paper-based
      checksheet that the residents carry with them. The checksheet will help us
      identify which information sources are used, at various times and frequencies.
      Interviews with the residents using these checksheets should provide additional
      details of how utility of the resource, disadvantages of the resource, etc.
      Specific Goals The goals of our current study include: (1) direct observations of
      residents PDA usage to determine how this compares to our previous results
      (above), ts (above), (2) determine if PDA usage varies between outpatient and
      inpatient clinics, (3) determine how different information sources are used in
      these clinics. Our long range goal includes considering how PDAs might improve
      the information gathering processes by identifying useful PDA applications, along
      with user interfaces residents find intuitive.

PMID- 14728290
TI  - Evaluation of standardized tasks for primary care physicians using the MOXXI
      electronic prescribing and integrated drug management system.
AB  - The Medical Office for the Twenty First Century (MOXXI) is a research project
      testing the potential benefits of an electronic prescription and drug management
      system for primary care physicians. This system includes a dynamic electronic pad
      for prescription entry with fields for treatment indications; a drug profiler
      with a graphic representation of the list of prescription medications purchased
      in the last year; a refill compliance calculator; dates of emergency room visits
      and hospital admissions; cost of drugs dispensed; and an alert system that
      detects interactions among drugs, treatment duplications, and contraindications
      with certain allergies or specific diseases. One concern expressed by physicians
      that could influence uptake and acceptability is the increased time that may be
      required to use the system. User abilities are a factor in this process, as well
      as user interface, user training and system speed.

PMID- 14728291
TI  - An application of Geospatial Information System (GIS) technology to anatomic
      dental charting.
AB  - Historically, an anatomic dental chart is a compilation of color-coded symbols
      and numbers used within a template, either paper or computerized, to create a
      graphic record of a patient's oral health status. This poster depicts how
      Geospatial Information System (GIS) technology can be used to create an accurate,
      current anatomic dental chart that contains detailed information not present in
      current charting systems.

PMID- 14728292
TI  - The physician's perception of medical error and its application to the
      development of an educational training tool.
AB  - It is becoming clear that if we are to impact the rate of medical errors it will
      have to be done at the practicing physician level. The purpose of this project
      was to survey the attitude of physicians in Alabama concerning their perception
      of medical error, and to obtain their thoughts and desires for medical education
      in the area of medical errors. The information will be used in the development of
      a physician education program.

PMID- 14728293
TI  - Electronic data collection tools for quality improvement: antibiotic utilization
      project.
AB  - The project goal is to provide data on patterns of broad-spectrum antibiotic use
      in a pediatric clinic by utilizing electronic data collection tools. This was
      carried out as a quality improvement project sponsored by a local health network
      and one of its affiliated pediatric clinics. Pharmacy data was available to show
      relative rates of broad-spectrum antibiotic use, but this data was not linked to
      diagnostic categories or to total patient visits. There was also a lack of data
      showing the influence of related clinical factors and of shared decision-making
      between parents and physicians. Data to elucidate these factors was obtained with
      handheld computers used by physicians and with a web survey tool was used by
      patients and staff.

PMID- 14728294
TI  - Developing a metadata data model for the National Health and Nutrition
      Examination Survey (NHANES).
AB  - The National Health and Nutrition Examination Survey (NHANES), developed by the
      Centers for Disease Control and Prevention (CDC), is a large and comprehensive
      health survey utilizing leading edge technologies to produce national estimates
      of health measures and the nutritional status of the U.S. population. Early
      NHANES metadata models grouped data by categories with little specificity and
      often not capturing the complexity of the survey. Subsequently, existing models
      at the Census Bureau, CDC, and the EPA were evaluated in addition to industry
      standards, such as DDI, Dublin Core, and ISO 1179. For the NHANES metadata model,
      the DDI standard and CDC Public Health Conceptual Model were chosen as the
      backbone for constructing the data model. The new model has led to increased data
      accuracy and several value-added products for producing codebooks, automatically
      checking questionnaire skip patterns, and producing questionnaire
      instrumentation.

PMID- 14728296
TI  - Survivable authentication for health information systems.
AB  - Possible solutions to establish a survivable authentication framework in a health
      information system including the one based on one-time passwords (OTPs) are
      discussed. A new convenient method to generate OTPs is proposed.

PMID- 14728297
TI  - Graphical visualization and navigation of genetic disease information.
AB  - One of the goals of biomedical scientists in this exciting era of molecular
      biology is the discovery of novel genes and their relationship to the molecular
      basis of disease. Part of this information connecting the geno-type to the
      phenotype is already known and available through hubs such as LocusLink. Although
      Locus-Link is a valuable resource that organizes curated information around genes
      and provides links to other online resources, it has not been developed for users
      to visualize graphically the association between genes and diseases, nor to
      navigate easily from genotype to phenotype (and back) within the same
      application. The application we developed, g2p, aims at visualizing graphically
      and navigating genetic disease information, especially the link between genotype
      and phenotype. The information displayed comes from a LocusLink query on human
      genes associated with a known disease (1330 genotypes, 1835 phenotypes, and 2050
      associations). This application is based, in part, on the graph visualization
      package GraphViz. Starting from a disease query, g2p displays the phe-notype view
      (Figure 1). Alternatively, from a gene query, it creates a genotype view (Figure
      2). In the example here, a search on the disease Bladder cancer leads to several
      genes, including RB1 (Figure 1). The double frame around RB1 indicates that it is
      linked to more than one disease and thus is "navigable". Following this link
      leads to the several diseases associated with RB1, including - besides Bladder
      cancer - Retinoblstoma and Osteosarcoma (Figure 2). The latter disease also has a
      double frame, indicating that several genes are associated with it.

PMID- 14728298
TI  - A colorimetric characterization of the raw digital data of the Visible Human
      Dataset images.
AB  - A colorimetric characterization of the all about 9 thousand Visible Human Dataset
      (VHD) cryosectioned color images of the male and female body is described here.
      Such characterization is performed keeping limited the computational time besides
      the high resolution of the considered VHD images. The about 27 thousand distinct
      histograms obtained are downloadable from the VHD Milano Mirror Site ftp server.

PMID- 14728299
TI  - TrialDB: A web-based Clinical Study Data Management System.
AB  - Clinical Study Data Management Systems (CSDMSs) are a class of software that
      support centralized management of data generated during the conduct of clinical
      studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such
      systems, which are typically deployed at an institutional or organizational
      level, must accommodate diverse types of data from different clinical domains
      that is generated by different groups of clinical investigators. Large-scale
      CSDMSs typically employ a high-end database engine that is usually accessed over
      an intranet or the Internet using Web-based technologies. CSDMSs in institution
      wide use for a variety of clinical domains are best served by entity-attribute
      value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are
      aware of use EAV design. However, de novo development of EAV databases for data
      management is a challenging task. A large body of generic metadata-driven code
      must be developed before a basic EAV application can be written. Clearly, the
      availability of pre-existing software with the requisite functionality would be
      very valuable. We will discuss the benefits of such software being in open-source
      form.

PMID- 14728301
TI  - Information seeking in the NICU: resident and faculty perspectives.
AB  - Little is know about how physicians utilize sources of patient information in
      complex medical environments such as the NICU. We conducted a qualitative study
      to investigate what sources of patient information physicians prefer to use in
      this setting. Results reveal a preference for physicians to use conversations
      with colleagues and the bedside flowsheet the majority of the time. Notes written
      by physicians - especially resident physicians - were used less frequently

PMID- 14728302
TI  - The Certainty-Agreement diagram: comparing the functionality of coding schemes in
      primary care clinical information systems.
AB  - Despite enormous investment of effort and resources there are few formal
      comparative evaluations between different coding schemes. We have recently
      described a methodology of a randomised crossover trial comparing the performance
      of Clinical Terms Version 3 (CTV3) and Read Codes 5 Byte set (RC5B) coding
      schemes in General Practice. 1 This study looked at the comparative performance
      of the two coding schemes by 10 general practitioners using a total of 995
      concepts extracted from clinical records. This paper describes the use of the
      Certainty-Agreement diagram in providing a graphical representation of
      comparative functionality.

PMID- 14728303
TI  - UMLS language and vocabulary tools.
AB  - A variety of resources developed for use with the Unified Medical Language System
      are presented. These resources include the UMLS Knowledge Source Server, the
      SPECIALIST lexicon, a set of lexical tools that work with the SPECIALIST lexicon,
      and a variety of other NLP document processing tools. These tools manage lexical
      variation, tokenize and parse text strings, suggest spelling variants, and
      provide text-to-concept mapping capabilities. The UMLS Knowledge Source Server is
      available under a license agreement. The other tools are freely downloadable.

PMID- 14728304
TI  - The Advanced Immunization Management (AIM) e-Learning Project.
AB  - New tools to educate immunization managers in developing countries are needed to
      keep these health policy makers current on the latest vaccines and procedures,
      and to provide support in decision making. The goal of the AIM e-Learning Project
      is to deliver up-to-date and engaging web-delivered media, with solid
      instructional design, to an audience relatively new to web-based learning.
      Accuracy of information and accessibility drive our design. Our ultimate
      objective is to aid immunization managers in developing timely, effective and
      sustainable policy.

PMID- 14728305
TI  - An online consumer health information resource: 3-year usage summary.
AB  - Partners Health Online is a portal to a broad set of consumer health information.
      As such, the site allows public access to health and disease information as well
      as Partners-specific information resources (e.g., departments, physicians,
      clinical trials, classes, support groups). Partners Health Online licenses its
      health care articles from Healthwise, Inc. This poster describes patterns of
      activity at Health Online over a 3-year period. The data were analyzed in terms
      of traffic patterns, visitor characteristics, and information-seeking behavior.

PMID- 14728306
TI  - Systems development in a complex stakeholder environment: NTCP Chronicle 2.0.
AB  - The CDC's National Tobacco Control Program (NTCP) is developing it's Chronicle
      2.0 an online grant application and progress reporting system. This system in
      it's 1.0 version is used by 51 CDC-funded state tobacco control programs to
      facilitate the collection of state data supporting progress on key performance
      measures. This poster highlights the application development process for
      Chronicle 2.0 and presents lessons learned.

PMID- 14728307
TI  - Diagnoses, syndromes, and diseases: a knowledge representation problem.
AB  - Despite their widespread use, the terms "syndrome", "disease" and "diagnosis" are
      sometimes utilized improperly and ambiguously, compounding the complexities of
      medical knowledge representation. The definitions and illustrative examples
      provided here will be useful for developers of diagnostic expert systems.
      Description of the Problem Representing medical knowledge is a highly complex
      endeavor. The improper use of the terms "syndrome", "disease" and their relations
      to "diagnosis" is one of the difficulties with which medical informaticians must
      deal, especially when developing expert systems to support diagnoses. Although
      ubiquitous in medical and lay discourse, the term "disease" has no unambiguous,
      generally accepted definition. How-ever, most of those using this term allow
      themselves the comfortable delusion that everyone knows what it means. Only
      sparse and fragmented literature could be found regarding this issue.

PMID- 14728308
TI  - Assessing explicit error reporting in the narrative electronic medical record
      using keyword searching.
AB  - In this study, we assessed the explicit reporting of medical errors in the
      electronic record. We looked for cases in which the provider explicitly stated
      that he or she or another provider had committed an error. The advantage of the
      technique is that it is not limited to a specific type of error. Our goals were
      to 1) measure the rate at which medical errors were documented in medical
      records, and 2) characterize the types of errors that were reported.

PMID- 14728309
TI  - SysBank: a knowledge base for systematic reviews of randomized clinical trials.
AB  - The Systematic Review Bank (SysBank) is a structured knowledge base that captures
      information about the design, execution, and results of systematic reviews of
      randomized controlled trials (RCTs). The SysBank data model has been adapted from
      RCT Bank, a knowledge base of randomized trials, and refined using three
      published systematic reviews. SysBank links directly to the RCT Bank entries of
      studies included in the systematic review. SysBank builds upon RCT Bank to
      support computer-assisted evidence-based medicine.

PMID- 14728310
TI  - Wireless application for complex wound management.
AB  - This project was to develop a web based wireless system to be used by community
      care nurses. Wound care constitutes approximately one half of home health care
      nursing visits. The system was implemented with a digital camera and a handheld
      computer with a wireless connection to a web based server. A database was used to
      control access to the clinical cases and to serve as a data repository. When new
      images were uploaded to the server a wound expert was notified via pager. The
      images and data could be viewed from any computer with an internet connection.

PMID- 14728311
TI  - Critically Appraised Topics (CAT) peer-to-peer network.
AB  - A peer-to-peer network of Critically Appraised Topics or CATs would allow sharing
      of relevant clinical information regarding specific clinical problems among
      physicians. This proposed network would enable clinicians to develop and share
      CATs to other users within the network. This poster describes a proposed
      implementation of a peer-to-peer internet based sharing of critically appraised
      topics in the Philippines.

PMID- 14728312
TI  - Canada Health Infoway - a pan-Canadian approach.
AB  - Canada Health Infoway is a non-profit corporation created and funded by the
      federal government of Canada in 2000. Its initial focus is to accelerate the
      implementation of an electronic health record (EHR) on a pan-Canadian basis as
      well as produce an EHR blue print by 2007. The organization is a major investment
      for Canadians with a $1.1 billion budget, but substantial long-term healthcare
      savings are expected due to Canada Health Infoway's involvement.

PMID- 14728313
TI  - Assessing the impact of user interface to the usability of a clinical decision
      support system.
AB  - In a clinical decision support system (CDSS), the outcome of the system is
      related to the user interface directly. A successful CDSS should offer an
      efficient user interface to clinicians in order to get the most proper
      consultation results. This study is to assess the impact of user interface to the
      usability of CDSS. Two different types of input user interfaces were integrated
      into a well-established CDSS, namely, keyword-based interface and menu-based
      interface. The operating time of each interface was assessed, and the efficiency
      of the interfaces, effectiveness of the systems, and enjoyment of the users were
      also evaluated for degree of usability.

PMID- 14728314
TI  - Automated identification of shortcuts to patient data for a wireless handheld
      clinical information system.
AB  - Inadequate access to patient information at the point of care has been identified
      as an impediment to the health care process. To create clinical computing tools
      that are useful to and used by clinicians, developers of clinical information
      systems must have accurate models of the users for whom their systems are
      intended. To create these models, the information needs of clinicians must be
      understood. While the wireless handheld environment offers many advantages such
      as the ability to provide mobile access to information, there are a number of
      challenges. Developing for this environment differs from the laptop and desktop
      environments due to features such as processing power, screen size, input
      mechanism, and bandwidth. PalmCIS (Palm-based Clinical Information System) is a
      clinical application being developed at New York Presbyterian Hospital (NYPH)
      that provides clinicians with access to patient data via a wireless handheld
      device. We are using an automated technique to uncover patient-specific
      information needs of clinicians while using a patient record system. With the
      results, we can enhance PalmCIS.

PMID- 14728315
TI  - A real time interface between a computerized physician order entry system and the
      computerized ICU medication administration record.
AB  - Prior attempts to interface ICU Clinical Information Systems (CIS) to Pharmacy
      systems have been less than successful. The major problem is that in ICUs,
      medications frequently have to be administered and charted in the CIS Medication
      Administration Record (MAR) before pharmacists can enter them into the Pharmacy
      system. When the Pharmacy system belatedly sends medication orders to the CIS
      MAR, this may create duplicate entries for medications that ICU nurses have had
      to enter manually to chart doses actually given. The authors have implemented a
      real time interface between a Computerized Physician Order Entry (CPOE) system
      and a CIS operating in ten ICUs that solves this problem. The interface transfers
      new medication orders including order details and alerts directly to the CIS
      Medication Administration Record (MAR), where they are immediately available for
      nurse charting. METHODS: The Patient Care Expert (PCX) web-based CPOE system was
      developed at Cedars-Sinai Medical Center and interfaced to a CIS serving 133 beds
      in 10 ICUs (CareVue CIS, Philips Medical Systems, Andover, MA). The CPOE used an
      existing CIS interface specification available for Pharmacy systems. At other CIS
      sites Pharmacy interfaces had enjoyed limited success because in many cases, ICU
      nurses had to manually add drugs to the MAR to chart urgent and emergent doses.
      When physician orders were finally processed by the Pharmacy, the orders sent to
      the CIS were frequently posted on the MAR as duplicate entries, causing confusion
      in the medical record. Although the PCX CPOE was interfaced to the hospital's
      Pharmacy system, for ICU patients all medication orders were transmitted to the
      CIS MAR. As soon as a physician authenticated orders with an electronic signature
      (Figure 1), all medication orders appeared in the CIS MAR, ready for the nurse to
      verify the orders and then chart doses. The medications shown in gray in Figure 2
      are new automatic entries the nurse will authenticate with an electronic
      signature. Once authenticated, nurses may chart individual doses Results: 40,170
      ICU medication, IV infusion and IV drip orders were automatically transferred
      from the CPOE to ICU CIS MARs during three months of CPOE operation. The
      interface eliminated manual order transcription, medication entry errors and
      improved ICU nurse efficiency and satisfaction.

PMID- 14728316
TI  - Exploring out-patient behaviors in claim database: a case study using association
      rules.
AB  - Patient behaviors are affected by so many factors that makes it is not easy to
      describe by simple measures. Our approach bases on finding association rules,
      which is widely used in marketing to identify their customers. We found rules
      describing complex patient behavior from huge claim dataset and we grouped them
      into several groups for a better understanding.

PMID- 14728317
TI  - An experimental system for comparing speed, accuracy, and completeness of
      physician data entry using electronic and paper methods.
AB  - Electronic medical record (EMR) systems have important potential advantages over
      traditional paper-based systems, but they require that physicians assume
      responsibility for data entry. However, little is known about the quality of
      physician data entry in electronic systems. This study describes a system for
      comparing the speed, accuracy, and completeness of examination data entry using
      electronic and paper methods. Data will be shown to demonstrate that this may be
      a simple, reproducible, and useful technique.

PMID- 14728318
TI  - Health information system for community-based multiple screening.
AB  - Disease screening is one of important activities in the domain of public health.
      However, traditional disease screening is based on solitary disease rather than
      multiple diseases. Although information accrued from multiple screening make
      contribution to health risk assessment as well as efficient management, data
      sources underpinning multiple screening are diversified and complicated including
      registration, primary data from questionnaire or biological measurement, referral
      system, confirmatory diagnosis, and case management. As our multiple screening
      integrates five types of cancers and four types of chronic disease at each out
      reach and ambulatory setting, packages for attendants vary according to age,
      gender and risk factor (such as betel chewing, alcohol drink, smoking, family
      history, self-disease history, etc.). We took the initiative in design of health
      information system to support the complex processes of multiple screening. To
      enhance the efficiency of multiple screening and efficient disease management,
      health information system was therefore designed to support such a complicated
      infrastructure.

PMID- 14728319
TI  - Adapting current Arden Syntax knowledge for an object oriented event monitor.
AB  - Arden Syntax for Medical Logic Module (MLM)1 was designed for writing and sharing
      task-specific health knowledge in 1989. Several researchers have developed
      frameworks to improve the sharability and adaptability of Arden Syntax MLMs, an
      issue known as "curly braces" problem. Karadimas et al proposed an Arden Syntax
      MLM-based decision support system that uses an object oriented model and the
      dynamic linking features of the Java platform.2 Peleg et al proposed creating a
      Guideline Expression Language (GEL) based on Arden Syntax's logic grammar.3 The
      New York Presbyterian Hospital (NYPH) has a collection of about 200 MLMs. In a
      process of adapting the current MLMs for an object-oriented event monitor, we
      identified two problems that may influence the "curly braces" one: (1) the query
      expressions within the curly braces of Arden Syntax used in our institution are
      cryptic to the physicians, institutional dependent and written ineffectively
      (unpublished results), and (2) the events are coded individually within a curly
      braces, resulting sometimes in a large number of events - up to 200.

PMID- 14728320
TI  - Sharing infobuttons to resolve clinicians' information needs.
AB  - Attempts to link clinical information systems to on-line information resources
      date back over a decade. The World Wide Web presents new opportunities to create
      such links, which we refer to as "infobuttons". This capability is partly due to
      the ease with which a link (called a Uniform Resource Locator, or URL) in one Web
      based system can take users to another Web-based system, and partly due to the
      proliferation of high-quality Web-based resources. Typically, contextual
      information from the clinical system (such as patient data) is passed to a search
      engine that is evoked and, in turn, presents search results to the user.
      Impediments to infobutton development include customized programming to pass
      context information to the information resource, lack of standards for types and
      values of context information, variability of search engine interfaces, and a
      lack of understanding of clinicians' information needs. We are addressing these
      limitations with an Infobutton Manager (IM) that provides a standardized
      interface for matching user contexts to information resources.

PMID- 14728321
TI  - Use of a data warehouse to monitor simvastatin tablet splitting.
AB  - A data warehouse was used to examine the LDL levels for patients who were
      switched from whole to half tablets of simvastatin. The LDL levels were available
      both pre and post conversion. 7,321 patients were switched and the LDL levels for
      these patients were tracked. 1,408 patients had a slight increase in LDL (less
      than 15% above baseline). Those patients whose LDL increased by greater than 15%,
      and was above 120 mg/dl, were switched back to whole tablets.

PMID- 14728322
TI  - The integration of similar clinical research data collection instruments.
AB  - We devised an algorithm for integrating similar clinical research data collection
      instruments to create a common measurement instrument. We tested this algorithm
      using questions from several similar surveys. We encountered differing levels of
      granularity among questions and responses across surveys resulting in either the
      loss of granularity or data. This algorithm may make survey integration more
      systematic and efficient.

PMID- 14728323
TI  - Evaluating a health information resource in a health system.
AB  - In an effort to offer the broadest scope of quality information resources,
      libraries are often faced with decisions related to the sources they provide
      based on the quality and cost of each resource. However, there lacks a framework
      to evaluate these resources to maximize the value of services offered to library
      users. The Claude Moore Health Sciences Library collaborated with the Department
      of Health Evaluation Sciences to undertake a comprehensive evaluation project to
      begin to establish such a framework. The long term goals are to: 1) determine
      cost effectiveness of services provided on an ongoing basis to provide objective
      basis for pursuing or renewing licenses, 2) evaluate licensed health care
      information services/databases under consideration and 3) create a process for
      ongoing evaluation. This abstract reports the results of the first demonstration
      evaluation of an information resource, MDConsult, as a model for future
      evaluation studies in a library setting.

PMID- 14728324
TI  - Order sets utilization in a clinical order entry system.
AB  - An order set is a predefined template that has been utilized in the standard care
      of hospitals for many years. While in the past, it took the form of pen and
      paper, today, it is, indeed, electronic. Within order sets are distinct ordering
      patterns that may yield fruitful results for clinicians and informaticians,
      alike. Protocols like there electronic counterpart, order sets, provide an
      'indication' identifying the clinical scenario of the patient's condition when
      the ordering event occurred. This 'indication' is rarely captured by individual
      orders, and provides difficult challenges to developers of information systems.
      While mandating an 'indication' be entered for every medication or lab order
      makes the job much more tasking on the physician provider, it is appealing to
      researchers and accountants. We have attempted to bypasses that consideration by
      identifying ordering patterns that predict diagnostic related codes (DRGs) and
      diagnostic codes which would greatly facilitate the information gathering process
      and still provide a flexible and user friendly physician interface.

PMID- 14728325
TI  - A process for consolidation of redundant nursing documentation forms.
AB  - Form redundancy can lead to duplicate documentation which can be the source of
      patient and staff frustration, as well as data errors. A data-driven systematic
      process for consolidation of the multiple redundant forms used in various patient
      care areas across a health care delivery system is proposed and tested using the
      21 intake forms currently used by a regional HMO.

PMID- 14728326
TI  - Creating knowledgebases to text-mine PUBMED articles using clustering techniques.
AB  - Knowledgebase-mediated text-mining approaches work best when processing the
      natural language of domain-specific text. To enhance the utility of our
      successfully tested program-NeuroText, and to extend its methodologies to other
      domains, we have designed clustering algorithms, which is the principal step in
      automatically creating a knowledgebase. Our algorithms are designed to improve
      the quality of clustering by parsing the test corpus to include semantic and
      syntactic parsing

PMID- 14728327
TI  - Family-oriented cardiac risk estimator: a Java web-based applet.
AB  - We developed a Java applet that calculates four different estimates of a person's
      10-year risk for heart attack: (1) Estimate based on Framingham equation (2)
      Framingham equation estimate modified by C-reactive protein (CRP) level (3)
      Framingham estimate modified by family history of heart disease in parents or
      siblings (4) Framingham estimate modified by both CRP and family heart disease
      history. This web-based, family-oriented cardiac risk estimator uniquely
      considers family history and CRP while estimating risk.

PMID- 14728328
TI  - A technique to improve the spelling suggestion rank in medical queries.
AB  - Correct spelling is crucial for online search engines to function well, and
      health information is highly sought after online. We propose a technique for
      increasing the effectiveness of spell-checking tools for use with medical
      queries. Our results show a marked improvement in the ranking of the correct term
      within the suggestion list returned by the spelling correction tool, as well as a
      lessening of the drawbacks associated with using larger dictionaries.

PMID- 14728329
TI  - VUMeF: extending the French involvement in the UMLS Metathesaurus.
AB  - A considerable number of robust vocabularies and thesauri have been developed for
      the healthcare and biomedical domain. No single vocabulary, however; provides
      complete coverage of the information needs from a public health perspective. The
      results of an investigation of vocabulary sources for the development of a
      comprehensive controlled vocabulary for the public health domain at the Centers
      for Disease Control and Prevention (CDC) is presented.

PMID- 14728330
TI  - Assessing home care agencies' readiness for telehealth.
AB  - Home healthcare is facing a set of challenging new realities in the 21st century
      such as funding limitations and increased life expectancy. Many believe that the
      use of telehealth enabling patients at home to interact with nurses at the
      clinical site using videoconferencing technology, will be a cost-effective
      solution to providing quality care services. Many agencies have adopted or are
      planning on implementing a telehealth solution. Level of agencies' readiness can
      lead to a lower level of risk, and a more successful innovation outcome. We
      developed a framework for assessing home care agencies' readiness for telehealth
      consisting of 35 items. This instrument can be used as a decision support tool
      for agencies that are about to implement a telehealth system as well as a
      formative or summative evaluation tool for agencies already utilizing telehealth.

PMID- 14728331
TI  - A meta-data model for knowledge in decision support systems.
AB  - Clinical decision support such as alerts, reminders and guidance are driven by
      rules often distributed among a variety of applications in a healthcare
      information system. Due to the increasing size of rule bases, there is a growing
      need to manage this dispersed knowledge in an integrated environment. A system
      for management of executable clinical knowledge such as rules should (1) assist
      in the development and maintenance of rules throughout the rules' life-cycles,
      (2) support search and retrieval of rules in the knowledge base (e.g., rules for
      diabetes, rules created by a particular individual), and (3) facilitate the
      analyses of rules in the knowledge base (e.g., identify rules not updated in the
      last year). In order to create such a clinical knowledge management system it is
      necessary to model the meta-data of rules. There have been efforts to document
      meta-data about rules within the Arden Syntax Medical Logical Modules' project.
      However, the maintenance and library categories in that project allow mainly free
      text information about a rule. We have created a comprehensive meta-data
      structure and taxonomy for describing clinical rules that supports the features
      of a knowledge management system. We also tested this model using a
      representative set of rules.

PMID- 14728332
TI  - Core problems reported by students in a palm OS and Internet-based problem entry
      system predicts performance on the third-year internal medicine clerkship.
AB  - CWeblog is a web and palm OS-based system used by medical students to record the
      problems and diagnoses of patients encountered in third-year clerkships at the
      Uniformed Services University. Data is available for analysis by clerkship
      directors as soon as it is entered. A pretest is given on the first day of the
      internal medicine third-year clerkship (the clerkship), and the National Board of
      Medical Examiners shelf examination (NBME) is given during the final twelfth
      week. Internal medicine specialty societies publish a list of 20 core problems in
      internal medicine to be emphasized during the third-year clerkship.

PMID- 14728333
TI  - Delphi rating on the internet.
AB  - We designed an application to allow respondents to rate components of clinical
      guidelines on the Internet. Twenty-three invited experts completed the rating
      followed by a satisfaction survey using a 5-level Likert scale. The experts felt
      that Web data entry was convenient, acceptable and easily accessible. We conclude
      that Web-based Delphi rating for consensus development is a convenient and
      acceptable alternative to the traditional paper-based method.

PMID- 14728335
TI  - Electronic access to care system: improving patient's access to clinical
      information through an Interactive Voice Response (IVR) system and Web portal.
AB  - Our clinical providers spend an estimated four hours weekly answering phone
      messages from patients. Our nurses spend five to ten hours weekly on returning
      phone calls. Most of this time is spent conveying recent clinical results,
      reviewing with patients the discharge instructions such as consults or studies
      ordered during the office visits, and handling patients' requests for medication
      renewals. Over time this will lead to greater patients' dissatisfaction because
      of lengthy waiting time and lack of timely access to their medical information.
      This would also lead to greater nursing and providers' dissatisfaction because of
      unreasonable work load.

PMID- 14728334
TI  - Efficient web-based navigation of the Foundational Model of Anatomy.
AB  - The University of Washington's Foundational Model of Anatomy (FMA)1 is a complex,
      frame-based model composed of over 170,000 frames collectively specified by more
      than 1.4 million slot values. The Foundational Model Explorer (FME) was designed
      to provide simple and intuitive web access to this complex knowledge base. The
      Foundational Model Explorer (FME) (Figure 1) is built upon the Protege 2000
      knowledge base access library [http://protege.stanford.edu/]. The FME
      application, associated libraries, and the FMA database all reside on remote
      servers. Users of the FME are not required to download, install, or set-up any of
      these components. The FME application, in response to a query, retrieves the
      appropriate information from the FMA, formats these data into html documents, and
      transmits them, via the Internet, back to the client where they can be viewed
      from any standard web browser

PMID- 14728336
TI  - A web and handheld based diagnosis & procedure tracking system.
AB  - Personal computing devices such as personal organizers, handheld PC's, and tablet
      PC's are becoming common tools in clinical care and medical education. There is
      an increasing need for these devices to track various tasks students and medical
      trainees perform. In particular, in undergraduate medical education, there is a
      need for tracking the depth and breadth of each student's clinical encounters
      over the course of his or her education. The authors have developed an
      application which allows for easy and rapid deployment of a tracking system for
      medical students' experiences during their clinical training years.

PMID- 14728337
TI  - Physicians' attitudes regarding patient access to electronic medical records.
AB  - Prior to the implementation of Electronic Medical Record (EMR) web access for
      patients at a large integrated delivery systems, we surveyed physicians?
      attitudes. Our web based questionnaire revealed largely positive attitudes about
      access. The exceptions included abnormal reports, progress notes, and e-care. A
      factor analysis identified the group of physicians who didn?t view patients as
      partners felt most negative about the process.

PMID- 14728338
TI  - The Lilongwe Central Hospital Patient Management Information System: a success in
      computer-based order entry where one might least expect it.
AB  - Computer-based order entry is a powerful tool for enhancing patient care. A pilot
      project in the pediatric department of the Lilongwe Central Hospital (LCH) in
      Malawi, Africa has demonstrated that computer-based order entry (COE): 1) can be
      successfully deployed and adopted in resource-poor settings, 2) can be built,
      deployed and sustained at relatively low cost and with local resources, and 3)
      has a greater potential to improve patient care in developing than in developed
      countries.

PMID- 14728339
TI  - Using rough sets, neural networks, and logistic regression to predict compliance
      with cholesterol guidelines goals in patients with coronary artery disease.
AB  - Coronary artery disease is a leading cause of death and disability in the United
      States and throughout the developed world. Results from large randomized,
      blinded, placebo-controlled trials have demonstrated clearly the benefit of
      lowering LDL cholesterol in lowering the risk for coronary artery disease.
      Unfortunately, despite the quantity of evidence, and the availability of
      medications that can efficiently lower LDL cholesterol with few side effects, not
      everyone who could benefit from cholesterol lowering interventions actually
      receives them. Despite the dissemination of national care guidelines for the
      evaluation and treatment of cholesterol levels (NCEP - National Cholesterol
      Education Program), compliance with such guidelines is suboptimal. There clearly
      is room for improvement in narrowing the gap between evidence based guidelines
      and actual clinical practice. The ability to classify those patients who are or
      will likely to be noncompliant on the basis of patient data routinely collected
      during patient care could be potentially useful by enabling the focusing of
      limited health care resources to those who are or will be at high risk of being
      under treated. In order to explore this possibility further, we attempted to
      create such classifiers of cholesterol guideline compliance. To do this, we
      obtained data from an ambulatory electronic medical record system at use at the
      MGH adult primary care practices for over 20 years. We obtained the data from
      this hierarchically-structured EMR using its own native query language, called
      MQL (Medical Query Language). Next, we applied to the collected data the machine
      learning techniques of rough set theory, neural networks (feed forward
      backpropagation nets), and logistic regression. We did this by using commonly
      available software that for the most part is freely available via the internet.
      We then compared the accuracy of the classifier models using the receiver
      operating characteristic (ROC) area and C-index summary metrics.

PMID- 14728340
TI  - Experience in designing and evaluating a Teleconsultation System supporting
      shared care of oncological patients.
AB  - This poster present our experience in designing, developing and deploying a Web
      based Teleconsultation System based on a Patient Centered Oncological Electronic
      Medical Record (PEMR) specifically de-signed to provide clinicians a cooperative
      work tool supporting the oncological patient management. An evaluation phase in a
      clinical setting was performed when the system was deployed in the hospitals. A
      second evaluation phase after two year of utilization has been carrying on.

PMID- 14728341
TI  - Practical evaluation of clinical guideline document models.
AB  - This project evaluates existing XML document models for the representation of
      clinical guidelines, as part of an effort to determine the best model to encode
      IHC's Care Process Models. The best model will be selected on the basis of its
      ability to support "Infobutton" queries at the point of care.

PMID- 14728342
TI  - Using computational modeling to study the impact of workplace characteristics on
      patient safety outcomes.
AB  - How do patient characteristics, organization characteristics and patient care
      unit characteristics interact to affect quality, safety, and cost outcomes? What
      changes can nurse managers make on their units that will optimize outcomes for
      their patients? To answer these questions, we are collecting data from 35 nursing
      units in 12 hospitals in Arizona, and using the results as a basis for
      computational modeling. Although it has been used in clinical research, until now
      computational modeling has had little application to healthcare or nursing
      organizations. In this poster session, we describe our application of Orgahead, a
      computational modeling program.

PMID- 14728343
TI  - ADDUp.org: Administration on Developmental Disabilities Updates Project.
AB  - The Oregon Institute on Disability and Development (OIDD), the has developed an
      integrated Web site and searchable database to serve as a portal to information
      on the programs of the Administration of Developmental Disabilities (ADD) to
      enable them to collaborate more efficiently and also to showcase their work to a
      broad and diverse audience. The site has been designed to exceed current
      standards in Web accessibility and meet the interface needs of a diverse group of
      people with disabilities.

PMID- 14728344
TI  - Development of gene ontology tool for biological interpretation of genomic and
      proteomic data.
AB  - We have designed and developed a Gene Ontology based navigation tool, GoMiner,
      which organizes lists of interesting genes from a microarray or a protein array
      experiment for biological interpretation. It provides quantitative and
      statistical output files and useful visualization (e.g., a tree-like structure)
      to map the list of genes to its biological functional categories. It also
      provides links to other resources such as pubmed, locuslink, and biological
      molecular interaction map and signaling pathway packages.

PMID- 14728345
TI  - Interpreting hypernymic propositions in an online medical encyclopedia.
AB  - Interpretation of semantic propositions from bio-medical texts documents would
      provide valuable support to natural language processing (NLP) applications. We
      are developing a methodology to interpret a kind of semantic proposition, the
      hypernymic proposition, in MEDLINE abstracts. In this paper, we expanded the
      system to identify these structures in a different discourse domain: the Medical
      Encyclopedia from the National Library of Medi-cine's MEDLINEplus Website.

PMID- 14728346
TI  - A prototype system for retrieval of gene functional information.
AB  - Microarrays allow researchers to gather data about the expression patterns of
      thousands of genes simultaneously. Statistical analysis can reveal which genes
      show statistically significant results. Making biological sense of those results
      requires the retrieval of functional information about the genes thus identified,
      typically a manual gene-by-gene retrieval of information from various on-line
      databases. For experiments generating thousands of genes of interest, retrieval
      of functional information can become a significant bottleneck. To address this
      issue, we are currently developing a prototype system to automate the process of
      retrieval of functional information from multiple on-line sources.

PMID- 14728347
TI  - Results from the fielding of the Bio-surveillance Analysis, Feedback, Evaluation
      and Response (B-SAFER) system in Albuquerque, New Mexico.
AB  - Public health authorities need a surveillance system that is sensitive enough to
      detect a disease outbreak early to enable a proper response. In order to meet
      this challenge we have deployed a pilot component-based system in Albuquerque, NM
      as part of the National Biodefense Initiative (BDI). B-SAFER gathers routinely
      collected data from healthcare institutions to monitor disease events in the
      community. We describe initial results from the deployment of the system for the
      past 6 months

PMID- 14728348
TI  - Impact of a personalized decision support aid on menopausal women - results from
      a randomized controlled trial.
AB  - To improve menopausal counseling, we developed a computer-generated personalized
      menopause decision support aid (DSA) and measured its impact in a randomized,
      controlled trial. Results suggest that this DSA may help women make informed
      decisions about menopausal therapy, change their risk perceptions, and motivate
      behavioral change.

PMID- 14728349
TI  - Frequency of laboratory test utilization in the intensive care unit and its
      implications for large scale data collection efforts.
AB  - Mapping of local use names to standardized naming schemas such as LOINC" micro is
      a time consuming and difficult task when done retrospectively or during the
      configuration of new information systems. We found that a relatively small number
      of tests and profiles (106 to 205) represent 99% of all testing done in 3 ICUs
      studied. In addition, all of the lab studies needed for the most commonly used
      ICU scoring systems fell into the top 23 lab studies and profiles performed in
      each ICU studied. We have identified a subset of the LOINC database which,
      because of their frequency of use, should be the focus of efforts to bring naming
      uniformity to ICU information systems.

PMID- 14728350
TI  - Extraction of a local linear trend from physiological time series.
AB  - We discuss methods for robust signal extraction from noisy physiological time
      series as measured in intensive care. The aim is a method which allows a fast and
      reliable de-noising of the data and separation of artifacts from relevant changes
      in the patients condition. For approximating local linear trends we use robust
      regression estimators. We examine the performance of the L1 regression, the
      repeated median and the least median of squares for this task.

PMID- 14728351
TI  - The Virtual Slide Set - a curriculum development system for digital microscopy.
AB  - We describe the development of a Virtual Slide System for creating and viewing
      clinico-pathologic cases with embedded interactive digital microscopy. The system
      supports rich text-to-image annotation, including (1) hotlinks of text
      descriptions that move the student to the correct part of the slide, and (2)
      annotations such as arrows and circles that appear on the Virtual Slide on
      request. The interface can be configured by the student to alter the degree of
      guidance the system provides. The authoring layer provides a graphical user
      interface to authors for creating new case sets, cases, questions, and annotated
      virtual slides, which are saved to a database and automatically added to the
      Virtual Slide homepage. The system has been used in two pilot studies at the
      University of Pittsburgh.

PMID- 14728352
TI  - Improving the human computer interface design for a physician order entry system.
AB  - The computerized physician order entry (CPOE) system has become a primary focus
      of time and monetary investment in the healthcare arena. This focus is partly due
      to the need to reduce medical errors that occur due to illegibility, drug
      interactions, and misplaced decimals. A CPOE system can potentially prevent many
      of these errors, resulting in a significantly safer healthcare system. However,
      only one-third of the hospitals in the United States have installed CPOE systems,
      and only 1 percent of these require the physicians to use them.1 The success and
      failure of such a system is dependent on the acceptance by the users, in this
      case, the physicians. Unfortunately, many of the CPOE systems are not designed to
      address usability issues. They are hard to use, hard to learn, and they often
      generate user frustrations and abandonment. In this project, the user interface
      of one such software program was analyzed. As a result of this analysis, a
      prototype was developed as a component of the system to offer alternative
      solutions to the identified usability problems.

PMID- 14728353
TI  - Primary care clinician attitudes towards electronic clinical reminders and
      clinical practice guidelines.
AB  - Compliance with outpatient practice guidelines is low and clinical reminders have
      had variable success in improving adherence rates. We surveyed primary care
      physicians (PCPs) regarding practice guidelines and the perceived utility of
      electronic reminders for both routine health maintenance (HM) items and chronic
      disease management. Most PCPs preferred receiving reminders in an electronic
      format rather than a paper format. Electronic reminders were felt to be more
      useful for HM items than for diabetes management. The majority of clinicians felt
      that electronic reminders significantly improved overall health care quality.

PMID- 14728354
TI  - Emergency implementation of knowledge management system to support a bioterrorism
      response.
AB  - In a public health emergency, it becomes necessary for public health agencies to
      provide timely, accurate and useful information to the community. During the
      anthrax attacks, the Public Health Practice Program Office in the Centers for
      Disease Control and Prevention implemented a knowledge management (KM) system to
      respond to an increased number of inquiries from public health officials, first
      responders, and health care professionals as well as the general public. While it
      is possible to successfully implement a knowledge management system quickly in a
      crisis situation, additional challenges to sustainability may result from
      shortchanging the normal decision-making channels.

PMID- 14728355
TI  - One size does not fit all: interpreting laboratory data in pediatric patients.
AB  - Results of laboratory tests for kidney stone risk factors are reported based on
      adult reference ranges and are not readily interpretable in children. We have
      developed a solution which converts laboratory output to appropriate pediatric
      patient-adjusted relative units, compares results using age-specific reference
      ranges, and flags out-of-range values. The example presented demonstrates how
      clinicians with technical skills can use existing computer resources to develop
      effective solutions to problems they experience in clinical practice.

PMID- 14728356
TI  - A national survey of emergency department triage in Sweden.
AB  - The aim of this study was to identify the organisation of and knowledge about
      triage work in Swedish emergency departments (ED) as a first step to
      understanding what is necessary for decision support in ED triage systems in
      Sweden. A national survey using telephone interviews for data collection was
      used. Results showed great variety in how work regarding ED triage is organised
      and performed. The variety occurs in several areas including education, personnel
      performing triage, facilities available and scales used.

PMID- 14728357
TI  - Characterizing information needs and cognitive processes during CIS use.
AB  - Medical errors are often associated with inadequate cognitive processing that is
      based upon impaired access to information.1 Understanding the information needs
      of nurses and physicians' when using a clinical information system (CIS) is
      difficult largely because there are few systematic attempts made to do so. We
      collected 15.5 hours of data of nurses and physicians' CIS interactions in three
      clinical environments (cardiac ICU, a general medical/surgical nursing, and an
      ambulatory clinic). We accomplished this through observational, cognitive-based
      methods (e.g., thinking aloud during interaction) and the video capturing of
      events with a portable usability laboratory.2 We developed a systematic approach
      to identify and define in-context clinical information needs while using a CIS,
      and determine how to categorize and code such events. 3

PMID- 14728358
TI  - CRC Tissue Core Management System (TCMS): integration of basic science and
      clinical data for translational research.
AB  - The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9
      geographically distributed sites conducting a program of research including both
      basic science and clinical components. The CRC TCMS was designed to capture and
      integrate basic science and clinical data sets. The system utilizes multiple data
      modeling methodologies and web-application platforms, and was designed with the
      high level objectives of providing an extensible, generalizable model for
      integrating data as required to conduct translational research.

PMID- 14728359
TI  - Decision support for governing boards of integrated delivery networks:
      explicating versus eliciting knowledge.
AB  - The everyday knowledge work of members of one governing health board was mapped
      using institutional ethnography. Our objective was to identify opportunities to
      improve the effective use of information and communication technologies for
      decision support. The dynamic interplay of work processes, professional
      discourse, institutional complexes and dominant ideology was explicated, that is,
      made visible in relation to the actualities of work practices.

PMID- 14728360
TI  - StarTracker: an integrated, web-based clinical search engine.
AB  - This poster details the design and use of the StarTracker clinical search engine.
      This program is fully integrated within our electronic medical record system and
      allows users to enter simple rules that direct formatted searches of multiple
      legacy databases.

PMID- 14728361
TI  - Enterprise-wide drug-drug interaction alerting system.
AB  - According to the Institute of Medicine's (IOM) 1999 report To Err is Human:
      Building a safer Health System, "medical errors kill some 44,000-98,0001 people
      in U.S. hospitals each year. Partners HealthCare System (PHS) is a large
      integrated delivery network in Boston, MA, which has as a goal improving patient
      care by preventing adverse drug events (ADE) and reducing medication errors
      enterprise-wide. PHS has developed a drug-drug Interaction (DDI) detection
      feature, for the suite of clinical applications currently used by its two major
      teaching institutions, Brigham & Women's Hospital (BWH) and Mass General Hospital
      (MGH). The following clinical applications will be using this drug-drug
      interaction feature: NICU Order Entry (OE) at BWH, MGH OE for pediatrics and
      adults, the Partners outpatient medical record, The LMR, and BICS OE at BWH.

PMID- 14728362
TI  - Use of the Internet for seeking health care information among young adults.
AB  - Little is known about what types of health information young adults seek online.
      A survey was conducted at a diverse community college to assess what health
      topics students seek online, and analyzed on the basis of smoking status. The
      most popular topic was found to be health/nutrition. Tobacco/smoking information
      was the least sought after topic even though 22% of the study group identified
      themselves as smokers.

PMID- 14728363
TI  - The challenge of negation in health care searches and queries.
AB  - This poster deals with exclusionary queries implemented using the database
      language SQL and the VA FileMan database system and the retrieval searches
      involving negated concepts in medical narratives. The poster describes and
      presents error patterns and designing database queries, underlying comprehension
      issues regarding negative statements and queries, strategies and software for
      avoiding false positives in searches, and makes practical recommendations on
      identifying potential sources of error and avoiding incorrect or misleading
      results.

PMID- 14728364
TI  - Information retrieval system for Japanese Standard Disease-code Master Using XML
      Web Service.
AB  - Information retrieval system of Japanese Standard Disease-Code Master Using XML
      Web Service is developed. XML Web Service is a new distributed processing system
      by standard internet technologies. With seamless remote method invocation of XML
      Web Service, users are able to get the latest disease code master information
      from their rich desktop applications or internet web sites, which refer to this
      service.

PMID- 14728365
TI  - Patient satisfaction with a Web-based patient-provider messaging system
      implemented across a statewide delivery system (Group Health Cooperative).
AB  - Since 1999, Group Health Cooperative has been developing and implementing Web
      services to improve patient access to health care. Among these services are a
      patient-provider secure messaging system and online pharmacy refills. A survey of
      patients using these services demonstrated the value of these tools in enhancing
      the patients' ability to manage their health care and the positive effects it
      could have on member retention.

PMID- 14728366
TI  - jTerm: an open source terminology server.
AB  - The consistent semantic transmission of clinical data between systems, and from
      system to user, is a key requirement for clinical information systems. The use of
      terminology servers to provide this functionality has been well articulated (1,
      2). We describe here an open source terminology server for use in clinical
      infrastructures.

PMID- 14728367
TI  - What factors determine the success of clinical decision support systems?
AB  - Computerized decision support systems (CDSS) which improve the quality of patient
      care are strong and necessary incentives for clinicians to use electronic medical
      records. We have noted previously that the logical path of CDSS design, which
      would be to determine the factors that predict success before the system is
      designed, appears rarely to have been followed. In this overview update of the
      literature on predictors of successful CDSS, we conclude that the predictors have
      not been adequately identified and the success of CDSS may improve when they are.

PMID- 14728368
TI  - Mobile technology in a clinical setting.
AB  - Wireless technology can offer clinicians access to the latest patient data when
      they are located outside of the hospital campus. It allows physicians to be more
      effective with their time by enabling a new method of delivering clinical
      information, thus improving patient care. Imagine being stuck in traffic, or at a
      conference in another state, when a call comes in for the patient's latest lab
      results. With a wireless handheld device, and a web-based application, the
      physician can access this information in minutes.

PMID- 14728369
TI  - Developing a patient intervention to reduce antibiotic overuse.
AB  - The emergence of drug resistance among common community-acquired bacterial
      infections has been clearly linked to the overuse of antibiotics. To address this
      problem, guidelines have been developed for the judicious use of antibiotics,
      particularly with regard to respiratory infection in adults and children. In
      addition, the CDC has promulgated guidelines for the general public, exhorting
      patients not to take an antibiotic for viral illnesses, not to pressure
      practitioners for antibiotic therapy, not to use antibiotics prescribed for
      another person, and not to use antibiotics left over from a previous illness.
      Despite some overall decline in antibiotic use, patients continue to engage in
      antibiotic overuse practices, resulting in increasing antimicrobial resistance.
      One reasons for antibiotic overuse is "antibiotic expectation," in which patients
      expect to be treated with an antibiotic for an acute infection, whether it is
      viral or bacterial.1 This phenomenon points to an underlying system of beliefs
      held by patients toward antibiotic use that may be alterable by educational
      interventions.

PMID- 14728370
TI  - A comparison of health information needs between patients at a suburban hospital
      based clinic and two underserved inner city clinics.
AB  - A needs assessment was conducted and the results were analyzed to determine and
      compare the health information seeking habits and needs of outpatients at a
      suburban hospital-based clinic and at two clinics located in underserved areas of
      the inner city.

PMID- 14728371
TI  - Factors contributing to computer system downtime in the emergency department.
AB  - Little research has been conducted on the nature and impact of system downtime.
      Downtime may have a major impact both on patient care and on operating costs. We
      examined different system components that contributed to downtime of an emergency
      department information system and characterized the frequency and length of these
      downtimes during a period of four months.

PMID- 14728372
TI  - Balance model and patient safety.
AB  - Improving patient safety has been largely focused in recent years. Medical
      related errors have been pointed as the leading cause of death and injury in the
      United States. One of the causes of medical error is impaired information
      transfer and communication. The purpose of this study is to use balance theory to
      better understand how information is transferred between patients and health care
      providers and the interactions among balance theory elements at the ambulatory
      surgery settings. Results can be used to improve information transfer and
      communication process.

PMID- 14728373
TI  - Predicting cranial computed tomography results of head injury patients using an
      artificial neural network.
AB  - We conducted this study to determine if artificial neural network modeling would
      predict cranial computed tomography results in head injury patients using
      different combinations of clinical variables. 150 consecutive patients admitted
      to a regional trauma center with head injury were enrolled in the study. The CT
      was labeled with presence of surgically significant intracranial hematoma (SSIH),
      if midline shift, obliteration of ambient cistern or basal cistern were found.
      The best performance of our models to differentiate normal from abnormal cranial
      CT and detection of SSIH was ideal.

PMID- 14728374
TI  - Housestaff use of medical references in ambulatory care.
AB  - We surveyed medical house officers at the Beth Israel Deaconess Medical Center
      during their ambulatory rotations about their utilization of reference materials,
      assessing such factors as frequency, the mode of reference, and specific choice
      of resources. The collected data were significantly illustrative of the shift
      from paper-based resources to digital references. These findings confirm that
      availability should be of utmost priority when designing references for
      physicians in training.

PMID- 14728375
TI  - Application of an XML-based document framework to knowledge content authoring and
      clinical information system development.
AB  - The role of XML in health care is evolving rapidly. Coupled with other W3C
      standards, informaticists can design systems that may be used not only for
      storage and retrieval of structured knowledge, but also for quick transformation
      of such knowledge into many different usable formats. At Intermountain Health
      Care, we are currently developing an XML-based document framework to accommodate
      both the capture of structured knowledge as well as its transformation into
      several usable formats. Our objective relies upon the premise that information
      systems can be implemented using workflows based on structured documents.

PMID- 14728377
TI  - Natural language processing challenges in HIV/AIDS clinic notes.
AB  - In recent years, significant progress has been achieved toward increased
      structured data entry using standardized health care terminologies. Concurrently,
      the value of narrative as the clinician's rich description of the encounter and
      source of vital information has been reaffirmed. Natural language processing
      (NLP) offers a strategy for integrating these approaches to provide structured
      reports for further computer processing. As part of a larger project aimed at
      using narrative data to enrich the online medical record, we analyzed a small
      sample of documents in a corpus of progress notes to identify potential
      challenges associated with using NLP for HIV/AIDS clinic notes. We provide
      illustrative examples of five types of challenges.

PMID- 14728378
TI  - Extracting diagnosis from Japanese radiological report.
AB  - This study is aimed at extracting diagnosis with positive or negative assertion
      from radiological report written in Japanese Natural Language. We get frequency
      of verb patterns that indicate pos/neg assertion, and extract a rule in order of
      the occurrence. We made customized dictionary of 36,152 terms relating to disease
      names or radiological findings, and tried to extract pairs of (pos/neg, disease
      and verb pattern ) by using rules according to the most frequent pattern from
      1,524/5,000 CT reports (each report consists of 15.1 words on the average). We
      tried only a few rules so far, and continue to find other rules.

PMID- 14728379
TI  - Just-in-time technology to encourage incremental, dietary behavior change.
AB  - Our multi-disciplinary team is developing mobile computing software that uses
      "just-in-time" presentation of information to motivate behavior change. Using a
      participatory design process, preliminary interviews have helped us to establish
      10 design goals. We have employed some to create a prototype of a tool that
      encourages better dietary decision making through incremental, just-in-time
      motivation at the point of purchase.

PMID- 14728380
TI  - Structuring healthcare knowledge bases: an analysis of explicit and implicit
      structures in Arden Syntax and an XML schema representation of Arden Syntax.
AB  - The Arden Syntax for Medical Logic Modules (MLMs) is an ANSI and ISO recognized
      standard language for representing clinical knowledge bases. We analyzed the
      explicit and implicit structures in Arden Syntax MLMs and developed an
      information model represented as an XML schema. While the explicit structures
      were easily represented as XML, implicit structures require further explicit
      definition. In any future representation format, explicit structuring must be
      balanced with expressiveness and usability.

PMID- 14728381
TI  - Evaluating a digital Resident Diagnosis Log: reasons for limited acceptance of a
      PDA solution.
AB  - Personal digital assistants (PDAs) offer opportunities to speed the process of
      data collection and analysis. We developed a PDA-based program, the Resident
      Diagnosis Assistant, which allows neurology residents to collect key diagnostic
      information about patients seen and treated and the upload this data into a
      departmental computer. Physicians often use the expenditure of their time to
      decide whether to accept a new device.

PMID- 14728382
TI  - The medical information sciences program of Amsterdam.
AB  - The medical information sciences program of Amsterdam has been in existence for
      15 years now. Starting in 1987, the program has been modified several times. Now
      a full-fledged 4 years master program exists. Students are taught skills to
      adequately and systematically apply information and communication technologies in
      order to optimize health care information processing. The program is offered
      within the Faculty of Medicine of the University of Amsterdam. The structure and
      contents of the current program will be described.

PMID- 14728383
TI  - An Electronic Medical Record system to support HIV treatment in rural Haiti.
AB  - HIV-AIDS has become the world's leading infectious cause of adult deaths.
      Approximately 5% of Haiti's adult population is infected with HIV, making it the
      most affected nation in the western hemisphere[1]. The non-governmental
      organization Zanmi Lasante (ZL) launched an innovative program 5 years ago to
      treat HIV patients in the very impoverished central plateau with highly active
      anti-retroviral therapy (HAART)[1]. ZL currently follows more than 4000 HIV
      positive patients, over 10% of whom are already on HAART, and was recently
      awarded funds from the Haitian grant from the Global Fund to fight AIDS,
      Tuberculosis and Malaria. Expanding treatment in a region with few doctors and
      virtually no roads, electricity, or electronic communication is a major challenge
      requiring careful coordination of clinical care, investigations and drug
      supplies. We describe a prototype Electronic Medical Record system to support
      treatment of HIV and tuberculosis in remote and impoverished areas.

PMID- 14728384
TI  - Mining microarray datasets aided by knowledge stored in literature.
AB  - DNA microarray technology produces large amounts of data. For data mining of
      these datasets, background information on genes can be helpful. Unfortunately
      most information is stored in free text. Here, we present an approach to use this
      information for DNA microarray data mining.

PMID- 14728385
TI  - Piloting web-based NAMCS data collection for nurse-managed centers.
AB  - Research consistently has shown that Nurse Practitioners (NPs) provide health
      care equivalent to that of physicians, and especially excel in patient education
      and case management, essential interventions to promote self-care in chronically
      ill ambulatory patients. Yet large-scale national studies have not been done.
      Nurse-managed centers are not included in the sampling frame of the National
      Ambulatory Medical Care Survey (NAMCS) and only 2.1% of the 2000 sample was from
      patient encounters with NPs.1 The aims of this pilot study were to create a web
      based format for the NAMCS; to expand it by adding selected nursing diagnoses,
      interventions, and outcomes; and to pilot-test it with 300 patient encounters in
      5 nurse-managed centers.

PMID- 14728386
TI  - Defining the priorities and challenges for the adoption of Information Technology
      in HealthCare: opinions from an expert panel.
AB  - The Harvard Interfaculty Initiative developed a tool to assess the level of
      Information Technology adoption at healthcare organizations and asked an expert
      panel to rate the clinical functions where IT-based solutions can impact quality
      of care. The experts were asked to identify high priority areas where IT might
      impact quality, and to rate the difficulty in implementation associated with that
      solution. While scores from the expert panel varied widely in assessing
      difficulties in implementation of IT, there was broad consensus on high priority
      areas.

PMID- 14728387
TI  - Clinicians' perceptions and the relevant computer-based information needs towards
      the practice of evidence based medicine.
AB  - We conducted a survey among 100 clinicians in a university hospital to determine
      the clinician's attitudes and the relevant computer-based information needs
      towards the practice of evidence-based medicine in outpatient setting.

PMID- 14728389
TI  - Development of user-centered interfaces to search the knowledge resources of the
      Virginia Henderson International Nursing Library.
AB  - This poster describes the development of user-centered interfaces in order to
      extend the functionality of the Virginia Henderson International Nursing Library
      (VHINL) from library to web based portal to nursing knowledge resources. The
      existing knowledge structure and computational models are revised and made
      complementary. Nurses' search behavior is captured and analyzed, and the
      resulting search models are mapped to the revised knowledge structure and
      computational model.

PMID- 14728388
TI  - A native XML database design for clinical document research.
AB  - Health-care institutions are gaining an increasing interest in exploiting the
      data that are gathered through electronic medical records. Narrative data,
      generated by transcription or direct entry, represents a far greater challenge
      for analytic tasks. Moreover, a small number of institutions are beginning to
      explore deeper structuring of narrative data using natural language processing
      (NLP). The data produced by NLP systems has a complex, nested structure. Current
      electronic medical records do not have the ability to store and retrieve data of
      this complexity in a suitable way.

PMID- 14728390
TI  - Proteomic patterns analysis: a new era of screening cancers.
AB  - Cancer is the second leading cause of death among Americans. It is estimated that
      1.28 million new Americans are diagnosed with cancer annually (1). The estimated
      overall annual cost of cancer being $171 Billion (1). Decreasing the costs of the
      screening and diagnostic tests will automatically decrease the total cost of
      cancer by limiting not only the direct medical costs but also by containing the
      indirect costs of morbidity and mortality. New screening and diagnostic tests are
      obviously needed. Screening methods are emerging in the evaluation of proteomic
      patterns. In proteomic pattern analysis, we can screen for not only one cancer
      but a chip may be able to screen for multiple cancers. New screening and
      diagnostic methods (2) investigated by NCI and FDA (3) (4) are correlating gene
      and protein expression patterns for early detection of cancer. Many papers have
      been published in the last 12 months (3) (4) (5) utilizing this new technique of
      molecular analysis in screening and diagnosing cancers with high sensitivity and
      specificity.

PMID- 14728391
TI  - Toward (semi-)automatic generation of bio-medical ontologies.
AB  - The design and construction of domain specific ontologies and taxonomies requires
      allocation of huge resources in terms of cost and time. These efforts are human
      intensive and we need to explore ways of minimizing human involvement and other
      resources. In the biomedical domain, we seek to leverage resources such as the
      UMLS Metathesaurus and NLP-based applications such as MetaMap in conjunction with
      statistical clustering techniques, to (partially) automate the process. This is
      expected to be useful to the team involved in developing MeSH and other
      biomedical taxonomies to identify gaps in the existing taxonomies, and to be able
      to quickly bootstrap taxonomy generation for new research areas in biomedical
      informatics.

PMID- 14728392
TI  - A comparison of self-documentation in diabetics: electronic versus paper diaries.
AB  - Attention needs to be given to how patients can capitalize on the benefits of
      Personal Digital Assistant technology. The specific aims of this pilot study are
      to compare the efficacy of diabetic patients documenting their health maintenance
      data (i.e. blood glucose levels, meal intake, and exercise) using an electronic
      patient diary (ED) versus a traditional pen and paper (PD) diary; and determine
      participants' satisfaction with each diary approach.

PMID- 14728393
TI  - Augmented Reality for teaching endotracheal intubation: MR imaging to create
      anatomically correct models.
AB  - Clinical procedures have traditionally been taught at the bedside, in the morgue
      and in the animal lab. Augmented Reality (AR) technology (the merging of virtual
      reality and real objects or patients) provides a new method for teaching clinical
      and surgical procedures. Improved patient safety is a major advantage. We
      describe a system which employs AR technology to teach endotracheal intubation,
      using the Visible Human datasets, as well as MR images from live patient
      volunteers.

PMID- 14728394
TI  - Technology failure analysis: understanding why a diabetes management tool
      developed for a Personal Digital Assistant (PDA) didn't work in a randomized
      controlled trial.
AB  - Managing Type 1 Diabetes Mellitus is a challenging feat especially for young
      patients. It is a tedious and demanding disease which requires painful self
      monitoring and injections multiple times per day. Many patients are unable to
      achieve good blood sugar control, in spite of strong evidence that good control
      leads to better outcomes. Many caregivers believe that more communication between
      caregivers and patients could lead to better control. This paper describes a tool
      that was developed to improve communication between caregivers and patients, its
      testing, how it failed to achieve its outcomes and recommendations for
      improvement.

PMID- 14728395
TI  - The map to LOINC project.
AB  - We describe a pilot project to standardize local laboratory test names to Logical
      Observation Identifier Names and Codes (LOINC) at five Indian Health Service
      (IHS) medical facilities. An automated mapping tool was developed to assign LOINC
      codes. The laboratory test names not mapped to LOINC by the mapping tool were
      assigned LOINC codes manually. The results achieved matched current benchmarks.

PMID- 14728396
TI  - Return on investment point of service Computerized Provider Charge Entry.
AB  - Provider charge entry systems offer many benefits to users and organizations. At
      Vanderbilt University Medical Center, a web-based provider charge entry system
      promises to deliver benefits in reducing days in accounts receivable, reducing
      labor required for claims and edit processing, and implementing business rules
      that deliver both strategic and financial benefits.

PMID- 14728397
TI  - Unicode, UTF-8, ASCII, and SNOMED CT.
AB  - SNOMED CT text files are encoded using UTF-8 to allow worldwide distribution and
      use of the terminology. Incorporating such UTF-8 encoded text into a system not
      currently using UTF-8 is simplified when the specific range of characters in the
      imported data is known. This poster describes the superset of ASCII found in the
      SNOMED CT US/UK Edition January 2003 release.

PMID- 14728398
TI  - Visual representation of cell subpopulation from flow cytometry data.
AB  - Flow cytometric systems are useful for protein identification and expression
      analysis, especially characterizing particular lineage or sublineage of cells. We
      clustered flow cytometry data of bone marrow cells into subpopulations using a
      clustering algorithm with its physical characteristics (cell size and cell
      granularity) and different molecular composition (cell reactivity with monoclonal
      antibodies). To display the cell subpopulations, we created a colored map
      according to the mean of 5 flow cytometry parameters based on a cluster. Such a
      map can reveal subpopulation properties that are not evident in the widely used
      scatter plot.

PMID- 14728399
TI  - Development of nursing care support system using PDA with wireless and barcode
      reader.
AB  - In this study, we developed nursing care support system using Personal Digital
      Assistants (PDA) with wireless and barcode reader. Our goals were to minimize the
      cost of deployment, to maximize the ease of operation, and to adapt to existing
      features and tasks of nursing care. The success of achieving these objectives was
      evaluated from the case study results involving system training session and trial
      of the system at a university hospital.

PMID- 14728400
TI  - Preliminary exploration of online social support among adults with asthma.
AB  - OBJECTIVE: Evaluate the qualitative and quantitative differences between
      moderated and unmoderated on-line social support groups focused on asthma.
      DESIGN: A retrospective study of a single months duration of Internet postings to
      four public on-line support groups focused on asthma. MEASUREMENT: Content
      analysis of random set of messages. RESULTS: Preliminary data indicate a
      quantitative and qualitative difference between moderated and unmoderated groups.
      Patterns of differences point to variations in the content of messages and the
      types of social support sought and provided.

PMID- 14728401
TI  - Classification of movement states in Parkinson's disease using a wearable
      ambulatory monitor.
AB  - For Parkinson's patients to function at their best, the clinicians who care for
      them must be able to manage and offset the fluctuations in movement that occur
      throughout the day. Symptoms of Parkinsonism such as bradykinesia, hypokinesia
      and akinesia and medication-related side effects such as dyskinesia need to be
      reported to the clinician in a manner that accurately conveys the timing and
      severity of symptoms. The clinician can then tightly adjust and titrate the
      timing and dosing of medication, allowing the patient to function at his or her
      best. Patient history and patient self reporting diaries are currently used for
      this purpose, but they have problems with compliance, completeness and
      reliability. A monitor that could be worn by the patient while he or she is at
      home and could issue to the clinician a report of how the patient has been moving
      over the course of the day would be a great help to clinicians. Wearable devices
      have been studied for the measurement of movement in Parkinson's patients, but
      none have been designed in a manner that would be useful for the titration of
      medications 1, 2, 3.

PMID- 14728402
TI  - Integrated breast diseases research and cancer registry in Turkey.
AB  - A system we call BDRS is implemented as an integrated disease specific system for
      breast diseases in order to obtain and use patient health data for clinical
      research, cancer registry and clinical care. It is an open, flexible and modular
      system that supports multi-institutional and multi-viewed utilization of health
      data. Three-tier web based architecture, and object oriented technologies have
      been employed to ensure its extendibility. Exchange and sharing of health data
      have been implemented with XML.

PMID- 14728403
TI  - Every user succeeds.
AB  - By applying proven models in user-interface design and training, we deployed a
      Web-based data collection and reporting system that has been enthusiastically
      embraced by users with limited computer equipment and skills. Social workers and
      nurses now submit forms paperlessly as they visit thousands of new mothers across
      seven counties. The value of the underlying database has been enhanced by
      immediate validity checks, up-to-the-minute summary reports, and instantaneous
      access to all previous entries.

PMID- 14728404
TI  - The use of data mining to investigate a possible quality problem with
      ultrasensitive HIV viral load data at a large reference laboratory.
AB  - Suppression of HIV viral load to <50 copies/mL, the lower limit of detection for
      the ultrasensitive assays, has been shown to correlate with favorable clinical
      outcome. Patients periodically exhibited transient or sustained low-level viremia
      based on this test. In order to investigate a possible quality concern, we used
      our corporate data warehouse to examine the patterns in our data over time as
      well as across geographic regions.

PMID- 14728405
TI  - Integrating mobile technology into a health professions curriculum: using
      flexible technology to meet expectations.
AB  - The diverse needs of students, faculty, administrators, and the curriculum
      itself, create formidable challenges when attempting to integrate mobile
      technology into a health professions curriculum. Single technology solutions
      often fail in this environment because they cannot meet user needs. Multiple
      platform and device agnostic solutions can provide the flexibility to address
      curricular needs without significantly adding technological complexity.

PMID- 14728406
TI  - Guideline interaction: a study of interactions among drug-disease
      contraindication rules.
AB  - To study the interactions among the drug-disease contraindiction guidelines in a
      real clinical setting by using clinical databases.

PMID- 14728407
TI  - KnowledgeLink update: just-in-time context-sensitive information retrieval.
AB  - Medical knowledge expands at a pace that makes it impossible for the individual
      clinician to keep up, especially for medications. Medication-related queries are
      the most common type of query that typically go unanswered during the course of
      providing care.1 Unanswered questions may result in errors, as found in one study
      evaluating systems failures associated with adverse drug events. This study found
      that better information might have prevented half of serious medication errors,
      and that lack of drug-specific knowledge accounted for the single largest
      proportion of these events (29%).2 While this information was available somewhere
      (either on paper or electronically), it was not at the providers' fingertips.
      Information technology should anticipate clinicians' needs, and bring the
      information they require to the point of care. For this purpose, we developed an
      application extender called KnowledgeLink, which provides "just-in-time" context
      sensitive information retrieval for drug-related queries.

PMID- 14728408
TI  - The knowledge modeling for chronic urticaria assessment in clinical decision
      support system with PDA.
AB  - The benefits of a clinical information system would be enhanced by a clinical
      decision support system (CDSS). We have developed urticaria diagnosis knowledge
      model for clinical practice. In order to construct a more accurate, evidenced
      based and comprehensive knowledge base for urticaria, we arranged and integrated
      knowledge from literatures-based knowledge, as provided by; The Korean Academy of
      Asthma and Allergy [1], the American Allergy Association based on an algorithm of
      chronic urticaria assessment. We presented this knowledge in a Boolean cross
      table frame and implemented these guidelines using the developed CDSS.

PMID- 14728409
TI  - Evaluation of a nurse care planning system that uses evidence-based order sets.
AB  - The results of an evaluation of a nurse care planning (NCP) system that is based
      on the use of evidence-based order sets will be presented. The integration of the
      nurse care planning function into the clinical information system (CIS) at
      Nebraska Health System (NHS) was implemented in March, 2003. The evaluation
      addresses the usability and completeness of the order sets to plan and direct
      nursing care.

PMID- 14728410
TI  - Thin client performance for remote 3-D image display.
AB  - Several trends in biomedical computing are converging in a way that will require
      new approaches to telehealth image display. Image viewing is becoming an
      "anytime, anywhere" activity. In addition, organizations are beginning to
      recognize that healthcare providers are highly mobile and optimal care requires
      providing information wherever the provider and patient are. Thin-client
      computing is one way to support image viewing this complex environment. However
      little is known about the behavior of thin client systems in supporting image
      transfer in modern heterogeneous networks. Our results show that using thin
      clients can deliver acceptable performance over conditions commonly seen in
      wireless networks if newer protocols optimized for these conditions are used.

PMID- 14728411
TI  - Secure de-identification and re-identification.
AB  - Today's healthcare organizations have both an ethical and legal responsibility
      for protecting patient privacy. However, the HIPAA privacy rule allows for the
      release of de-identified patient data for certain purposes. Secure encryption
      technology can be used to encrypt patient identified data so only the owners of
      the original data can re-identify the patient. It further allows consistent de
      identification over episodic collection events.

PMID- 14728412
TI  - Development of infobuttons in a wireless environment.
AB  - At Columbia-Presbyterian Medical Center, a clinical information system (CIS)
      called WebCIS is used by health care providers. We have developed a palm-based
      extension to WebCIS, called PalmCIS, which provides physicians access to clinical
      data through a wireless connection. As part of PalmCIS, we have added links to
      two on-line information resources: PubMed and Micromedex.

PMID- 14728413
TI  - Creating public health standard vocabularies: mapping a set of CDC's pathogen
      codes to SNOMED concepts.
AB  - CDC and its public health partners are conducting pilot projects designed to
      capture data directly from healthcare providers or to exchange existing data
      electronically.1 The translation of proprietary standards into the accepted
      national standards is a key part of this effort. This study mapped a set of
      pathogens within CDC's hospital infection control activities to The Systematized
      Nomenclature of Medicine (SNOMED) concepts and investigated the differences
      between the two.

PMID- 14728414
TI  - The development of variable MLM editor and TSQL translator based on Arden Syntax
      in Taiwan.
AB  - The Arden Syntax standard has been utilized in the medical informatics community
      in several countries during the past decade. It is never used in nursing in
      Taiwan. We try to develop a system that acquire medical expert knowledge in
      Chinese and translates data and logic slot into TSQL Language. The system
      implements TSQL translator interpreting database queries referred to in the
      knowledge modules. The decision-support systems in medicine are data driven
      system where TSQL triggers as inference engine can be used to facilitate linking
      to a database.

PMID- 14728415
TI  - Modeling interventions to improve access to public health information.
AB  - In a Robert Wood Johnson funded project, we established a model-based means for
      automatically analyzing and representing grey literature that reports on public
      health (PH) interventions. We summarize the development of an intervention model
      for public health documents and provide a project update on the implementation of
      natural language technology to improve access to difficult to find public health
      information.

PMID- 14728416
TI  - The use of SNOMED CT simplifies querying of a clinical data warehouse.
AB  - The usefulness of digital clinical information is limited by difficulty in
      accessing that information. Information in electronic medical records (EMR) must
      be entered and stored at the appropriate level of granularity for individual
      patient care. However, benefits such as outcomes research and decision support
      require aggregation to clinical data -- "heart disease" as opposed to "S/P MI
      1997" for example. The hierarchical relationships in an external reference
      terminology, such as SNOMED, can facilitate aggregation. This study examines
      whether by leveraging the knowledge built into SNOMED's hierarchical structure,
      one can simplify the query process without degrading the query results.

PMID- 14728417
TI  - The validity of an Internet-based Self-assessment Program for Depression.
AB  - The Internet-based Self-assessment Program for Depression (ISPD) has been found
      to have good test-retest reliability for major depressive disorder (MDD). The
      purpose of this study was to further examine the validity of the ISPD for MDD. We
      found sensitivity and specificity of MDD by ISPD to be 81.8% and 72.7%
      respectively. Internet may play an important role for patients to self-assess
      their possibility of getting MDD.

PMID- 14728418
TI  - Visual mapping for medical concepts.
AB  - Concept relationships are traditionally defined in human-generated vocabulary
      lists such as the Medical Subject Headings (MeSH). This poster describes a
      prototype system that automatically generates concept relationships from the
      medical literature. The system is directly connected to the PUBMED search engine.
      For any given medical concept, the system will generate two styles of visual maps
      from MEDLINE in real time. Users can use the maps to explore concept
      relationships or construct better search queries interactively.

PMID- 14728419
TI  - Role-based and Adaptive user interface designs in a Teledermatology consult
      system: a way to secure and a way to enhance.
AB  - User interface design is one of the most important parts of developing
      applications. Nowadays, a quality user interface must not only accommodate
      interaction between machines and users, but also needs to recognize the
      differences and provide functionalities for users from role-to-role or even
      individual-to-individual. With the web-based application of our Teledermatology
      consult system, the development environment provides us highly useful
      opportunities to create dynamic user interfaces, which lets us to gain greater
      access control and has the potential to increase efficiency of the system. We
      will describe the two models of user interfaces in our system: Role-based and
      Adaptive.

PMID- 14728420
TI  - Symptom assessment in home healthcare using digital pens.
AB  - We have developed a system allowing patients subject to palliative advanced home
      care to frequently submit symptom assessments from their homes. Using digital pen
      technology developed by Anoto AB, symptom assessments are transferred digitally
      over the GSM mobile phone network from the patient's home to the hospital clinic.
      The system is evaluated during spring 2003 at the hospital-based home care (HBHC)
      clinic of Linkoping University Hospital.

PMID- 14728421
TI  - DeTMan: a decision tree management tool for the Web and PDA environments.
AB  - Illness management protocols, often represented as decision trees, are used in
      many areas of medicine. Some clinical departments maintain numerous, often quite
      complex protocols. Protocol access in acute care situations can be challenging,
      especially when available only in hardcopy format. Access via the web and
      especially via personal digital assistants would be more helpful. In the absence
      of the prior availability of a general purpose web/PDA decision tree
      editor/navigator, we are developing such a tool.

PMID- 14728422
TI  - Communicable disease case entry using PDAs and public wireless networks.
AB  - Concerns about detecting and responding to attacks with biowarfare agents have
      resulted in the development of deployable case reporting systems, e.g. RSVP. We
      implement a proof of concept web-based information system to be used securely
      from personal digital assistants over public wireless networks, by public health
      field workers for routine and emergent case reporting. The system collects data
      for a local health jurisdiction, provides content- and event-based notification,
      and forwards case reports to the Colorado State communicable disease reporting
      system (CEDRS). We believe this demonstrates a useful integration of portable and
      web-based technologies with public health practice.

PMID- 14728423
TI  - Parsing free text nursing notes.
AB  - Parsing nursing notes requires tokenization, recognition of special forms,
      abbreviation expansion, and classification in the context of identified sections

PMID- 14728424
TI  - A method for subdividing clinical guidelines into process modules with associated
      triggers and objectives to facilitate implementation.
AB  - Representation of multi-step clinical guidelines (CG) and their implementation in
      computerized decision support (DS) systems are complex and logistically
      challenging tasks. However, many simple rules based on CGs (e.g., medical logic
      modules), have been successfully implemented through a few popular DS models
      (e.g., prevention reminders, order entry systems). To facilitate mapping of CGs
      to practical DS models, we propose an empirical method for sub-dividing CGs into
      modules according to the locus in a clinical process flow model where
      implementation would be most effective (e.g., post-encounter provider order
      entry). We further propose a classification of triggers and objectives for CG
      modules that provides a framework for a DS system to implement the module
      Successful application of the method to ten diverse CGs in the outpatient setting
      is described.

PMID- 14728425
TI  - A multi-interface adaptive hypermedia system to promote consumer-provider
      partnership in chronic disease management.
AB  - Much of chronic disease management depends on active partnership of consumer and
      provider. Our system promotes diabetes management through profiling and adaptive
      support of both consumer and provider. We use a University Podiatry Clinic and
      diabetes consumer information portal as inter-related contexts that share profile
      information.

PMID- 14728426
TI  - Mapping from a clinical data warehouse to the HL7 Reference Information Model.
AB  - Large-scale data integration efforts to support clinical and biologic research
      are greatly facilitated by the adoption of standards for the representation and
      exchange of data. As part of a larger project to design the necessary
      architecture for multi-institutional sharing of disparate biomedical data, we
      explored the potential of the HL7 Reference Information Model (RIM) for
      representing the data stored in a local academic clinical data warehouse. A
      necessary first step in information exchange with such a warehouse is the
      development and utilization of tools for transforming between local data schemas
      and standards-based conceptual data models. We describe our initial efforts at
      mapping clinical concepts from a relational data warehouse to the HL7 RIM.

PMID- 14728427
TI  - Adaptive filtering and prioritizing of diabetes consumer information for
      promoting consumer-provider partnership and communication.
AB  - To engender patient partnership in care we have designed an algorithm to filter
      and prioritize diabetes consumer information. This enables customized adaptive
      presentation for patients to highlight the most relevant issues. The profile for
      adaptation considers significant data (clinical and nonclinical), patient
      knowledge level and interests. An XML based implementation is the subject of
      ongoing experimental assessment.

PMID- 14728428
TI  - Factors affecting the sustainability of information technology applications in
      health care.
AB  - Biomedical informatics is a relatively new field; sustainability of information
      technology applications has not been studied in detail. We examined what factors
      contribute to sustainability in other fields (ecology, construction materials,
      business, primary health care, and environment and development). We describe some
      aspects of sustainability that can be applied to biomedical informatics:
      effectiveness, efficiency, financial viability, reproducibility, and portability.

PMID- 14728429
TI  - Concept and progress of a regional effort to improve blood lead reporting to six
      Western States by incorporating electronic laboratory reporting.
AB  - While electronic laboratory reporting (ELR) has the potential to be both more
      timely and complete than non-electronic data transmission and direct electronic
      data transfer can also reduce data input errors, these benefits are often
      underutilized. A survey of states in HHS Regions IX and X (Alaska, Arizona,
      California, Hawaii, Oregon, Washington) led to collaborative efforts to maximize
      ELR benefits on a regional scale. Collaboration outcomes included the
      ratification of a regional blood lead HL7 message format and the formation of a
      multi-state committee to address reporting discrepancies by the large regional
      labs to multiple states in the regions.

PMID- 14728430
TI  - Use of GLIF to model a behavioral intervention.
AB  - As a first step towards creating an ontology describing behavioral interventions,
      we created an ontology of PACE-Adolescent, a theory-based behavioral
      intervention, using PROTEGE-2000 and GLIF3. In the ontology, we were able to
      describe the overall behavioral protocol using GLIF3, adding additional ontology
      components to describe counseling actions, to enumerate behavioral theory
      constructs, and to link actions to constructs. We hope to work towards
      facilitating formal analysis of behavioral interventions and reuse and retesting
      of their components.

PMID- 14728431
TI  - Open-source toolkit for simple XML annotation.
AB  - Use of Extensible Markup Language (XML) is increasingly prevalent among medical
      informatics projects. Many of these projects involve, at some point, the
      interaction between a researcher and specialized XML documents for the purpose of
      annotating the XML data. We offer a simple toolkit to assist these researchers.
      Our solution is a simple, yet fully functional, annotation system that can easily
      be adapted to the needs of the researcher. All of the materials for this toolkit
      are freely available.

PMID- 14728432
TI  - Case reports on the Web redux: confidentiality still in jeopardy.
AB  - We reported at AMIA 1999 on the apparent lack of privacy protection for the
      subjects of case reports at 32 websites. It has been clear for some time that
      print journal editors and Institutional Review Boards require informed consent
      from patients or their surrogates if they can be potentially identified in
      publications. We found in 1999 that this level of confidentiality protection was
      not being applied to case reports on the Internet. This report is a follow up
      evaluation of those and 26 other websites with case reports to see if
      confidentiality protection practices have improved.

PMID- 14728433
TI  - The evolving neuroanatomical component of the Foundational Model of Anatomy.
AB  - In order to meet the need for an expressive ontology in neuroinformatics, we have
      integrated the extensive terminologies of NeuroNames and Terminologia Anatomica
      into the Foundational Model of Anatomy (FMA). We have enhanced the FMA to
      accommodate information unique to neuronal structures, such as axonal
      input/output relationships.

PMID- 14728434
TI  - Using respiratory-related calls to a nurse advice line to predict pediatric upper
      respiratory infection-related healthcare utilization.
AB  - Using Poisson regression analysis, respiratory-related calls to a nurse advice
      line in Denver, Colorado were used to predict pediatric upper respiratory
      infection (URI) outpatient and urgent care visits. Use of electronic hospital
      information systems and triage software allowed for the rapid identification of
      respiratory-related calls and URI-related utilization. Monitoring nurse advice
      line call volume may help increase awareness and planning for increases in
      healthcare utilization.

PMID- 14728435
TI  - Implementing wireless evaluation in a hospital-based OSCE center.
AB  - To provide an effective and efficient means to gather assessment data during
      Objective Structured Clinical Examinations [OSCEs] and integrate the data into
      ANGEL, the Indiana University School of Medicine's [IUSM] curriculum management
      system, a wireless approach using PDAs was selected, configured and evaluated.
      Following a systems architecture and human-computer interface analysis of the
      project, a system with less functionality but greater reliability was designed
      and implemented.

PMID- 14728436
TI  - Impact of CPOE order sets on lab orders.
AB  - Introduction of the computerized physician order (CPOE) is intended to promote
      best practices, decrease practice variation among practitioners, and optimize the
      utilization of resources consistent with evidence based practice guidelines.
      Implicit in the use of CPOE is the assumption that the use of order sets might
      decrease utilization of resources such as the ordering of unnecessary laboratory
      tests. Conversely compliance with practice guidelines may necessitate ordering of
      certain tests that are deemed to be consistent with the good practice of
      medicine. In order to develop an understanding of these issues, we compared the
      utilization of laboratory orders prior to and following implementation of order
      sets in CPOE. In addition, we analyzed the impact of CPOE on the timely placement
      of certain orders based on critical levels of some laboratory results, in this
      instance potassium.

PMID- 14728437
TI  - Tailored health communication: crafting the patient message for HIV TIPS.
AB  - The HIV TIPS project will pilot and evaluate the use of web-based information
      technology on prescription errors and quality of care by providing tailored
      practice guidelines and patient education in ambulatory practice settings of the
      National AIDS Education and Training Centers (NAETC) network. In the first phase
      of the project, we tailored messages to guide patient adherence and self-care,
      using DHHS guidelines. We developed a method based on communication theory to
      ensure complete and effective messages.

PMID- 14728439
TI  - Learner centered software design to empower physiology education.
AB  - Misconceptions in physiology undermine students' knowledge. New uses of
      technology in education offer interesting alternatives to correct these problems.
      This poster presents a design strategy based in user-centered design and the
      result of such process: an interactive program to support learning of respiratory
      physiology. This is an ongoing project, and future efforts will measure the
      effectiveness of this design tool in medical education.

PMID- 14728440
TI  - Residents' perspectives on the use of the Internet to improve infectious disease
      reporting.
AB  - Reports of infectious diseases to local and state public health agencies are
      often delayed and incomplete. Some of the clinicians charged with the
      responsibility for making notifications encounter various difficulties in
      reporting. These may include heavy patient loads that make it easy to forget to
      file reports, or cumbersome disease reporting mechanisms and systems. For some
      percentage of practitioners, knowledge of what and when to report infectious
      diseases is less than optimal. However, it is not clear how reporting methods or
      systems could be designed or improved, owing to lack of data on physicians'
      knowledge and views about them. We conducted a survey of resident physicians at
      three university teaching hospitals in Pennsylvania to ascertain their knowledge
      about reporting timeframe and responsibility, as well as their attitudes toward
      various methods to enhance disease reporting.

PMID- 14728441
TI  - The Genetics Home Reference: a new NLM consumer health resource.
AB  - The Genetics Home Reference (GHR) is a new information resource developed to be
      part of the National Library of Medicine's (NLM's) consumer health initiatives.
      The GHR's guiding principle is to make the health implications of the Human
      Genome Project accessible to the public. The GHR accomplishes this by providing a
      bridge between the NLM's consumer health systems MEDLINEplus and
      ClinicalTrials.gov on the one hand and the multiple resources emanating from the
      Human Genome Project on the other. The initial focus is on single gene conditions
      that are main topics in MEDLINEplus.

PMID- 14728442
TI  - A knowledge-based approach to information extraction from surgical pathology
      reports.
AB  - We describe the development of a prototype system for knowledge-based information
      extraction from surgical pathology reports. The current system includes abstract
      problem solving methods and a frame-based knowledge representation of body parts,
      procedures, diseases, and findings for prostate and breast cases. The system
      currently extracts the organ, procedure, and diagnoses, and sets an agenda of
      goals for further processing. A potential advantage of this approach is the
      ability to increase specificity of information extraction.

PMID- 14728443
TI  - Automatic learning of the morphology of medical language using information
      compression.
AB  - Conversion of free-text strings in a natural language to a standard
      representation (codes) is an important reoccurring problem in biomedical
      informatics. Determining the content of a string involves identifying its
      meaningful constituents (morphemes). One current method of identifying these
      constituents is to look them up in a preexisting table (lexicon). Manual
      construction of lexicons and grammars in complex domains such as biomedicine is
      extremely laborious. As an alternative to the lexico-grammatical approach, we
      introduce a segmentation algorithm that automatically learns lexical and
      structural preferences from corpora via information compression. The method is
      based on the Minimum Description Length (MDL) principle from classic information
      theory.

PMID- 14728444
TI  - ACKNOWLEDGE: a tool to support knowledge capturing.
AB  - Knowledge management enhances organizational competitive advantages by supporting
      the capture, maintenance and communication of the business processes knowledge to
      organization members. ACKNOWLEDGE is a tool that supports tacit and explicit
      knowledge capturing. Organization members can use this tool to exteriorize
      knowledge related to organizational processes activities. The acquired knowledge
      is filtered, packed and stored into the organizational memory in order to be
      reused by other members during processes activities execution.

PMID- 14728445
TI  - CardioKnowledge: a knowledge management environment.
AB  - Knowledge management supports decision-making by capturing and analyzing key
      performance indicators, providing visibility into the effectiveness of the
      business model, and by concentrating collaborative work and employee knowledge
      reviews on critical business problems. CardioKnowledge is a knowledge management
      environment based on the business and process requirements of a health care
      organization in Cardiology. CardioKnowledge supports organizational processes in
      order to facilitate the communication and exchange of knowledge among the
      cardiologists, medical students and other employees.

PMID- 14728447
TI  - Comparison of health/medical informatics curricula against multiple sets of
      professional criteria.
AB  - This poster expands on a methodology presented at the 2003 International Medical
      Informatics Association (IMIA) Conference on Education by analyzing the match
      between four graduate informatics programs to both the IMIA Working Group for
      Education (WG1) recommendations and the Certified Professional in Healthcare
      Information Management Systems (CPHIMS) exam objectives published by the
      Healthcare Information and Management Systems Society (HIMSS). Similarities and
      differences among the programs and criteria are described.

PMID- 14728446
TI  - Implementation and evaluation of an virtual intelligent agent.
AB  - Reference librarians at the National Library of Medicine answer over 100,000
      client questions annually. Although many answers are the NLM Web, clients may
      have difficulty finding them. Using intelligent virtual agent software, the NLM
      launched Cosmo, the Customer Service Owl (http://wwwns.nlm.nih.gov/). Cosmo uses
      natural language pattern matching to answer common questions. Early evaluation
      shows Cosmo can answer 25% of questions asked, but some users mistake the service
      for chat reference or a search engine.

PMID- 14728448
TI  - Comparing structural perspectives on Medical Informatics: EMBASE vs. MEDLINE.
AB  - Previous bibliometric analyses of Medical Informatics' internal structure used
      MEDLINE records as the unit of study. EMBASE, a product of Excerpta Medica,
      carries a wider international scope and offers complementary retrieval results to
      MEDLINE. Since much medical informatics critical thinking originated abroad and
      migrated to North America, this difference in coverage may also indicate a
      different perspective of "what constitutes medical informatics." Using
      traditional bibliometric and multivariate data analysis techniques, the present
      work examines EMBASE indexing records for the same 1995-1999 time frame as
      earlier MEDLINE studies to identify and compare structural features of the field.

PMID- 14728449
TI  - Development of competency-based on-line public health informatics tutorials:
      accessing and using on-line public health data and information.
AB  - In response to training and information needs of the public health workforce, the
      New York City Department of Health and Mental Hygiene, in collaboration with the
      Department of Biomedical Informatics, Columbia University and the New York
      Academy of Medicine, is developing a series of on-line, interactive tutorials in
      public health informatics. The goal is to teach public health practitioners how
      to locate, use, and disseminate data and information on the Internet, while
      imparting basic informatics principles. Course content is based on Public Health
      Informatics Competencies, and evaluation will be performed by measuring changes
      in self-efficacy and knowledge as well as determining user satisfaction.

PMID- 14728450
TI  - Web-based prediction of extubation outcome in premature infants on mechanical
      ventilation using an artificial neural network.
AB  - The web-based implementation of a decision-support tool for the prediction of
      extubation outcome in mechanically ventilated premature infants enables the
      integration of advanced and computationally intensive modeling approaches with
      easy-usage, no maintenance requirements and wide availability. Accordingly, the
      artificial neural network predictive tool developed provides decision-support in
      determining whether to extubate a premature infant to clinicians in NICUs
      anywhere with access to the Internet.

PMID- 14728451
TI  - Computerized antimicrobial decision support for hospitalized patients with a
      bloodstream infection.
AB  - We developed a computerized antimicrobial decision support program founded on our
      local bacterial susceptibility data. In a retrospective analysis of patients with
      a bloodstream infection, we compared the actual antimicrobials prescribed to the
      antimicrobials recommended by the program. We found the computer-guided therapy
      to be clinically and statistically more effective than the therapy initiated by
      the physicians. We conclude that computerized decision support can improve the
      targeting of empiric antimicrobial therapy.

PMID- 14728452
TI  - Does a state level acute hospital admitted patient dataset encapsulate
      appropriate performance measures of a process of care?
AB  - Strategically there is a need to not only take a clinical process view of health
      care delivery but also identify the appropriate information to support the
      processes. When considering the clinical process view, the challenge for
      continuous quality improvement is to eliminate inappropriate process steps, and
      continuously document performance/outcome. The questions are what performance
      measures are useful, and does a state level data collection capture relatable
      measures of a process of care.

PMID- 14728454
TI  - Nonsynonymous synonyms: correcting and improving SNOMED CT.
AB  - SNOMED CT was created from a merger of SNOMED RT and United Kingdom's National
      Health Service's Clinical Terms Version 3. The resulting terminology has a
      plethora of synonymous terms. This paper discusses how a review synonyms in the
      Procedure section of SNOMED CT revealed some nonsynonmous synonyms, hypothesizes
      why errors in synonymy may have occurred, and explains the steps taken to resolve
      nonsynonymous concepts previously assigned to synonyms.

PMID- 14728453
TI  - A Model of Computer-Mediated Social Support Among Older Adults.
AB  - Internet use has been growing exponentially, and older adults are one of the
      fastest growing online user groups. Due to the various physiological and
      psychosocial changes associated with aging, older adults are prone to social
      isolation. The Internet and e-mail may serve as a new source of support for older
      adults by connecting them with friends and family members, as well as providing
      useful information. In this study, based on prior research findings in sociology,
      communications, and informatics, A Model of Computer-Mediated Social Support
      Among Older Adults that explains relationships among a computer-mediated social
      network (CMSN), perceived functional social support from that network, and
      psychological well-being of community dwelling older adults was proposed. The
      primary purpose of this study was to test this model using Structural Equation
      Modeling (SEM).

PMID- 14728455
TI  - A proposed clinical decision support system (CDSS) output message.
AB  - When a clinical decision support system (CDSS) or other ancillary system detects
      an abnormal or problematic condition, healthcare providers must be notified in a
      timely manner so that appropriate corrective action can be taken. Delivery of
      clinical alerts to the appropriate providers is the role of a notification
      system.1,2 The content generating system must therefore communicate to the
      notification system the content to be delivered and any additional directives
      regarding the resulting notifications. This work is sanctioned by the Health
      Level Seven, Inc., Clinical Decision Support Technical Committee (CDS TC) and is
      based on previous proposals to the CDS TC.3 The proposed message model is
      presented as an XML schema.4

PMID- 14728456
TI  - Pilot study of an online dyspnea self-management program for COPD.
AB  - To address some of the shortcomings to providing timely and convenient education
      and support to patients with COPD, especially in the management of dyspnea, the
      Internet was considered a viable medium to deliver a previously tested program at
      a distance to reach more patients. Older COPD patients were able to participate
      in the program and most were very satisfied with the program. Changes were noted
      in dyspnea, support, self-efficacy, and exercise.

PMID- 14728457
TI  - Internet-based standardized patient simulation with automated feedback.
AB  - There exist many modalities for teaching and testing medical students. One method
      being explored is computer-based patient simulation. Traditionally, exposure to a
      variety of patients has been achieved through years of training under the
      supervision of experts in the field. Computerized patient simulation has been
      proposed as a method of creating a standardized patient care experience through
      algorithms and predefined patient findings. One study reported that after
      experience with computer-based simulation, 80% of students and mentors felt that
      it should be a mandatory part of medical education. Access to effective
      simulations with high-yield cases can be costly. Internet-based tools enjoy easy
      distribution and centralized maintenance. Simulations distributed via the
      Internet have proven successful in selected medical fields. Automated scoring of
      patient interactions has also been proposed as a way to eliminate the effort
      required for mentor evaluation.

PMID- 14728458
TI  - Protege-2000: an open-source ontology-development and knowledge-acquisition
      environment.
AB  - Protege-2000 is an open-source tool that assists users in the construction of
      large electronic knowledge bases. It has an intuitive user interface that enables
      developers to create and edit domain ontologies. Numerous plugins provide
      alternative visualization mechanisms, enable management of multiple ontologies,
      allow the use of interference engines and problem solvers with Protege
      ontologies, and provide other functionality. The Protege user community has more
      than 7000 members.

PMID- 14728459
TI  - Automated indexing of the Hazardous Substances Data Bank (HSDB).
AB  - The Hazardous Substances Data Bank (HSDB), produced and maintained by the
      National Library of Medicine (NLM), contains over 4600 records on potentially
      hazardous chemicals. To enhance information retrieval from HSDB, NLM has
      undertaken the development of an automated HSDB indexing protocol as part of its
      Indexing Initiative. The NLM Indexing Initiative investigates methods whereby
      automated indexing may partially or completely substitute for human indexing. The
      poster's purpose is to describe the HSDB Automated Indexing Project.

PMID- 14728460
TI  - Feasibility of a palmtop-based interactive education to promote patient safety.
AB  - Institute of Medicine defines "patient safety" as a set of measures taken by
      healthcare professionals to prevent adverse outcomes from medical errors. Kohn
      estimated that medical errors are likely to result in a death of 44,000 to 98,000
      people in U.S. hospitals each year, making it almost the fifth leading cause of
      death. The costs of medical errors, made by healthcare professionals, amount to
      $29 billions annually. Recent studies showed that current system of medical
      training and continuous education has limited capability in promoting and
      sustaining awareness of patient safety and medical error issues. Use of Personal
      Digital Assistants (PDA) has been increasingly widespread among clinical students
      and residents. Despite significant improvement in PDA functionality, current
      literature does not provide systematic assessment of potential use of hand-held
      computing for interactive clinician education. To address these issues, we
      assessed the feasibility of a PDA-based interactive multimedia tool aimed to
      provide self-paced patient safety education for clinicians.

PMID- 14728461
TI  - Interpretive Structural Modeling for introducing of image information system at
      the middle-scale hospitals.
AB  - We extract and analyze the decision factors of introducing image information
      system by ISM (Interpretive Structural Modeling) method to determine the criteria
      and structure for system selection. As a result, 15 factors were extracted, and
      the structure and relation among factors became clear.

PMID- 14728462
TI  - Social network analysis of gene expression data.
AB  - To investigate the structure of genomic interaction network, social affiliation
      network analysis was performed for the yeast gene expression compendium dataset
      of hundreds of systematic perturbations. Network density and centrality indices
      of genes and groups of genes revealed the core-peripheral and the significant
      intermediary players that may be critical for the control of the biological
      system.

PMID- 14728463
TI  - A needs assessment study for the Missouri Tele-hospice Project.
AB  - Hospice care focuses on palliation and the relief of suffering aiming to improve
      the quality of patients' last days. Telemedicine is considered to be a tool that
      can address challenges such as staff shortage, funding limitations and limited
      access to services in rural areas. Hospice services via telemedicine can be
      delivered directly into a patient's home by utilizing videoconferencing
      technology. The Missouri Telehospice Project aims to investigate the impact of a
      telehospice model on satisfaction with delivered care, caregiver burden, crisis
      prevention rates and overall cost of delivered care. Five urban and rural hospice
      agencies in Missouri are participating. A needs assessment study was conducted
      where hospice staff members responded to a set of questions within focus group
      and interview sessions providing feedback about the design, type of technology,
      frequency of usage and perceived impact on quality of hospice care.

PMID- 14728464
TI  - Healthcare website design for the elderly: improving usability.
AB  - Research shows that the elderly often use the Internet to search for healthcare
      information. Other studies show that many widely-implemented features of web site
      design may interfere with elders' ability to access the information they seek.
      This poster will illustrate principles of elder-friendly web site design by
      presenting a demonstration web site that provides information about neurological
      and psychiatric conditions for adults 50 years of age and older

PMID- 14728465
TI  - Integrating automated patient letter generation into the electronic medical
      record.
AB  - This poster describes the design and functionality of StarLetter, an electronic
      patient letter generation tool. StarLetter is integrated into the new results
      feature of the electronic medical record front end allowing the clinicians to
      generate electronic letters to patients within their workflow.

PMID- 14728466
TI  - Physician PDA use and the HIPAA Privacy Rule.
AB  - Physicians need better access to information when making patient care decisions.
      Hospitals should allow electronic data transfers to physician PDAs to improve
      patient care, and physicians must institute measures to secure the
      confidentiality of patient information on their PDAs. By explicitly excluding
      copies from their designated record set, hospitals need not maintain copies or
      track access of information on personally owned PDAs.

PMID- 14728467
TI  - Optimizing query response with XML user profile in mobile clinical systems.
AB  - Improvements of modern mobile technology, have created a need for a mobile
      clinical environment. In the field of mobile clinical systems, getting
      information on time is as important as mission critical aspects. However, web
      access time with the mobile device is still not feasible clinically. Therefore,
      the optimisation of query response becomes an important issue. We have developed
      a query optimising method using a user profile. We analysed user (clinician)
      specific queries in the medical field. Most of the data retrieval in the medical
      field is focused on the clinical test results, and the patient inverted
      exclamation mark s demographic information. Sometimes the information requested
      in the medical field places a heavy load on the database, since such information
      may require full database scanning and much joining of tables in the databases.
      In such cases, constructing profile data and employing it for data retrieval
      would help to improve the response time. The use of a predefined profile avoids
      the multiple joining process, and shortens the total response time. The object of
      our research is to improve query response by creating user profiles and using
      this profile information for patient data retrieval.

PMID- 14728468
TI  - Generating medical logic modules for clinical trial eligibility criteria.
AB  - Clinical trials are an important part of modern medical research, however the
      effort required to find candidates for participation in such trial is
      significant. With the increasing prevalence of electronic medical records,
      automated or semi-automated solutions become feasible. We present an semi
      automated approach for determining clinical trial eligibility based on
      information available in an electronic medical record.

PMID- 14728469
TI  - Interoperability of open source medical record systems.
AB  - This poster describes the open source medical system architecture and approaches
      for data sharing and interoperability.

PMID- 14728470
TI  - Using description logic to manage question corpora.
AB  - If clinical questions are to be used on a large scale as a practitioner interface
      to the medical knowledge base, improved methods must be developed for the
      semantic management of question corpora. In this project we investigate the use
      of description logic to manage question corpora. We propose the addition of a Q
      box to a standard Description Logic knowledge base. The Q-box will contain
      concept descriptions that are not yet accepted as part of the T-box, but in
      effect represent questions about concepts already described in the T-box.

PMID- 14728471
TI  - CRC Clinical Trials Management System (CTMS): an integrated information
      management solution for collaborative clinical research.
AB  - The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9
      geographically distributed sites conducting a program of research including both
      basic science and clinical components. To enable the CRC's clinical research
      efforts, a system providing for real-time collaboration was required. CTMS
      provides such functionality, and demonstrates that the use of novel data
      modeling, web-application platforms, and management strategies provides for the
      deployment of an extensible, cost effective solution in such an environment.

PMID- 14728472
TI  - Creating a note classification scheme for a multi-institutional electronic
      medical record.
AB  - How notes are categorized in an electronic medical record (EMR) influences how
      rapidly users can locate documents and enter new ones, whether algorithmic search
      for chart deficiencies is possible, and the ease of incorporating collections of
      existing notes. We balanced these competing needs when developing a note
      classification scheme for the Online Record of Clinical Activity (ORCA)
      electronic medical record at the University of Washington.

PMID- 14728473
TI  - Learning management systems' evaluation focuses on technology not learning.
AB  - Learning Management Systems (LMS) are widely used in educational institutions
      around the world. The purpose of this poster is to review the characteristics of
      evaluations of these systems consulting two kinds of sources: Peer-reviewed
      journals and Web documents. Our results show that the current emphasis is on
      evaluating the technology, which suggests the need for a theory/pedagogy driven
      evaluation focused on educational outcomes. Introduction

PMID- 14728474
TI  - Albumin versus crystalloid therapy in the management of hepatorenal syndrome: a
      model for using meta analysis in cost effectiveness studies and the design of
      clinical trials.
AB  - We applied traditional methods of gathering, integrating and summarizing findings
      of current literature, with new approaches for assessing the cost effectiveness
      of two treatments for hepatorenal syndrome (HRS). Findings of this cost
      effectiveness study are used to form a proposal for a multi-center prospective
      clinical trial, to assess the economic and clinical benefits of albumen versus
      crystalloid therapy in the care of these patients. Our initial findings suggest
      that albumin therapy is superior to standard crystalloid therapy, in the
      treatment of HRS patients. The number of survival days appears to increase with
      this form of therapy per dollar cost, while patients await liver transplantation.

PMID- 14728475
TI  - Information literacy: instrument development to measure competencies and
      knowledge among nursing educators, nursing administrators, and nursing
      clinicians: a pilot study.
AB  - This poster describes a pilot study conducted to establish validity and
      reliability of an instrument that will be used in a nationwide needs assessment,
      implemented to identify gaps in Information Literacy skills, competencies, and
      knowledge among key nursing groups nationally. Data and information gathered
      using the tool will guide the profession in developing appropriate education and
      continuing education programs to close identified gaps and enhance nurses'
      readiness for Evidence-Based Practice (EBP).

PMID- 14728476
TI  - Physicians' perceptions toward electronic communication with patients.
AB  - Despite the widespread use of email, electronic communication between physicians
      and patients is not part of the standard physician-patient relationship in the
      United States. Increased use of email may improve physician-patient
      communication, which is associated with improved patient satisfaction and health
      status. Evaluating email communication in this context is vital to minimizing
      potential risks and maximizing benefit to physicians and patients. We evaluated
      email use between physicians and patients, and physicians perceptions of the
      value and issues surrounding this form of communication in order to identify
      issues that would facilitate and improve electronic communication.

PMID- 14728477
TI  - A workflow model for adapting e-charts in specialty clinics.
AB  - Modeling of health professionals' activities and matching of these processes to
      applied information technologies are necessary for acceptance and optimal
      utilization of a clinical information system. The overall objective of this study
      was to describe the different processes involved in current clinical practice of
      neurologists and to estimate the extent by which these processes are standardised
      across neurologists. Results from this study will be used to optimise the
      deployment of a stroke e-record and provide insight on some of the
      characteristics that will need to be addressed.

PMID- 14728478
TI  - Mereotopological reasoning in anatomy.
AB  - Applications in the field of computer assisted Surgery (e.g. navigation,
      robotics, simulation) need consistent formal models of anatomical part-whole
      relationship (mereology) and neighborhood (topology) to enable automated spatial
      reasoning. We investigated mereotopological theories in terms of their
      suitability for providing a logical background for such models. The so far
      results indicate a need for a more spatially motivated classification of
      anatomical structures to allow a consistent and logical-based mereotopological
      modelling.

PMID- 14728479
TI  - Overcoming the barriers to the implementing computerized physician order entry
      systems in US hospitals: perspectives from senior management.
AB  - We sought to identify the barriers to CPOE implementation and the strategies for
      overcoming them. By analyzing 57 transcripts of interviews with management
      officials at 25 US hospitals, we identified costs and physician resistance as the
      two most significant barriers. Hospitals often overcome the high cost of CPOE
      implementation by placing patient safety at the top of their agenda. Other
      hospitals manage physician resistance by leveraging strong leadership, external
      influence, vendor commitment and the presence of house staff and hospitalists.
      Efforts to promote the adoption of CPOE should therefore focus on these
      strategies.

PMID- 14728480
TI  - An online communication tool alters the way patients find information.
AB  - Epilepsy Patients and users of an online educational and communication resource
      were polled about their information needs over time. Subjects appear to prefer to
      communicate with their specialist digitally rather than talk on the telephone or
      have a face-to-face visit. The longer the patients have access to the resource,
      the less likely they are to plan to make a face-to-face doctors office visit for
      information needs.

PMID- 14728481
TI  - A real application of a concept-based Electronic Medical Record.
AB  - We present a real implementation of a concept-based Electronic Medical Record for
      the management of heart failure disease. Our approach is based on GEHR archetypes
      represented in XML format for modelling clinical information. By using this
      technique it could be possible to build a interoperable future-proof clinical
      information system.

PMID- 14728482
TI  - Cure4Kids - building online learning and collaboration networks.
AB  - The International Outreach Program of St. Jude Childrens' Research Hospital has
      been developing programs to help countries with limited resources develop
      treatment centers to treat children with catastrophic diseases such as pediatric
      cancer and AIDS. Cure4Kids (www.cure4kids.org) is the Internet learning network
      that delivers medical education to doctors and nurses on pediatric cancer and
      AIDS. The objective of Cure4Kids is not only education, but also to provide tools
      for communications and collaborations among individuals.

PMID- 14728483
TI  - Evaluation of the implementation of an electronic medical record.
AB  - University of Minnesota Physicians, the faculty clinical practice organization of
      the Medical School, is implementing an Electronic Medical Record (EMR). During
      this process, we anticipated the need for an evaluative study of the
      implementation to examine process and satisfaction. This was in order to monitor
      the ability of the physicians to use the EMR effectively. The use of these data
      to evaluate the implementation and user-acceptance of change of process presents
      a unique research opportunity. The study of the impact of the EMR implementation
      on patient care, education, and other issues of academic interest make this
      research study valuable.

PMID- 14728484
TI  - Website to promote early detection of breast cancer: "www.thinkhealth.com".
AB  - We developed and studied a Website to promote breast cancer screening and allow
      women to access personalized risk and screening information. The site also
      provides a database of risk and screening information with multimedia
      enhancement, and direct interaction with experts and online communities. The site
      was studied to measure its effectiveness in motivating screening intentions and
      behaviors among a group of women subjects.

PMID- 14728485
TI  - Building an application framework for integrative genomics.
AB  - The accelerated pace of biological research and the current availability of whole
      genome data sets provides significant new sources of functional insight. We
      designed an architecture and framework for software to query and explore such
      data in an orderly and iterative fashion. The architecture is intended to provide
      an extensible platform for developing web based bioinformatics applications and
      to offer a flexible and end-user-extensible software environment to explore and
      integrate disparate biological data sources. This will enable the user to explore
      existing relationships and discover new functional relationships among these
      data.

PMID- 14728486
TI  - OpenGALEN: open source medical terminology and tools.
AB  - The GALEN programme of research into medical terminology began in 1991. In 1999
      OpenGALEN was formed to provide an open source route both for disseminating the
      results of that programme and as a framework for its future development.
      Currently available open source resources include a sophisticated ontology
      development environment and a large open source description logic-based ontology
      for the medical domain.

PMID- 14728487
TI  - Implementing a commercial rule base as a medication order safety net.
AB  - A commercial rule base was used to identify drug orders exceeding standard dosage
      limits at a university hospital. Initially, there were substantial numbers of
      clinically insignificant alerts. A method for altering the commercial rule base
      will be implemented to increase rule specificity for problematic drugs. With
      minor modifications, commercial rule bases can be used to rapidly create a safety
      net that screens drug orders for excessive dosages, while preserving the rule
      architecture for more finely tuned clinical decision support.

PMID- 14728488
TI  - Imaging : new electronic tool for clinicians.
AB  - The Imaging system captures clinical images, scanned documents, electrocardiogram
      (EKG) waveforms, and radiology images. Image and text data are provided in an
      integrated manner that facilitates the clinician's and nurses task of correlating
      the data and making patient care decisions in a timely and accurate way. It
      serves five important purposes: documents findings, makes images accessible to
      clinicians and nurses within the hospital, assists in conference decision making
      and education, aids in follow-up treatment of patients and facilitates
      telemedicine. The captured images are extremely helpful in follow-up care. The
      images are real time; so waiting time is decreased and patient care decisions are
      sooner. With the Image system, the process flow has completely changed. There is
      no longer a waiting time for x-ray's or EKG's to be brought to the units for the
      physicians or nurses to review, they can now access and view these reports from
      the computer at their work stations.

PMID- 14728489
TI  - Dose range checking in a computer order entry system.
AB  - We recently implemented a computer order entry (COE) system which uses decision
      support for dose range checking. In addition to providing decision support at the
      point of order entry via "alerts", the system tracks data regarding the
      occurrence of alerts related to dosing errors. We reviewed the dosing alerts for
      a "high risk" medications in a COE system. Telephone alerts were more likely to
      trigger alerts. There were more low dose than high dose alerts. Some alerts could
      be avoided by adjusting the threshold.

PMID- 14728490
TI  - Development methodology for a "next generation" medical informatics curriculum
      for clinicians.
AB  - We describe a new methodology for development of a medical informatics curriculum
      for practicing clinicians. The curriculum is based on a biaxial framework in
      which information is categorized by type of application and role of the learner
      in relation to the application. The curriculum development process incorporates
      feedback from practicing clinicians on an ongoing basis.

PMID- 14728491
TI  - Computerized reminders for syphilis screening in an urban emergency department.
AB  - Point of care reminders have been shown to be effective in changing ordering
      behavior in primary care settings, but electronic reminders in the emergency
      department have not been studied. We retrospectively evaluated a computerized
      system designed to prompt syphilis testing in an emergency department during an
      outbreak. Most individual reminders were not followed by a test. However, there
      was a marked general increase in syphilis testing.

PMID- 14728492
TI  - QuickSilver clinical tracker - a risk-management approach.
AB  - While many guidelines strive to automate the high-granular clinical thought
      process, the resulting risk stratification is often a low-granular management
      class (i.e. low, medium or high risk). Furthermore, the "low hanging fruit" of
      guidelines is not in decision support, rather in the subsequent action tracking.
      Therefore, we believe that only a small amount of data is required to produce
      significant reminders. In our approach, the clinician risk-stratifies the patient
      and enters the guideline at the management level. We do not attempt to replicate
      the clinical thought process; rather we ask the question, "Now that you have
      decided, how can we help track your decisions?" A risk-management approach
      encapsulates salient guideline features and provides a framework for basic
      decision support and data tracking.

PMID- 14728493
TI  - A randomized controlled trial of a patient-accessible electronic medical record.
AB  - Legal and technologic trends are making medical records more patient-accessible.
      The Health Insurance Portability and Accountability Act (HIPAA) stipulates that
      "patients must be able to see and get copies of their records, and request
      amendments." Medical records are more commonly being stored in electronically,
      and methods have been developed to share these records with patients in a secure
      format.1,2 Previous studies of patient-accessible medical records generally only
      provided limited exposure to the medical record and lacked controls for bias and
      confounding.3 We performed a 12-month randomized controlled trial of a patient
      accessible medical record to further assess the effects of such a program.

PMID- 14728494
TI  - Facilitating heart transplant candidate evaluation throughout Ohio.
AB  - The Ohio Solid Organ Transplantation Consortium (OSOTC) has a mission to ensure
      equitable access to transplant services to those most likely to benefit,
      regardless of personal resources. Patients are selected according to criteria
      established by the OSOTC, which are delineated in the Ohio Department of Health
      rule, and consistent with national criteria. The University of Cincinnati's
      Institute for Health Policy and Health Services Research (IHPHSR) has implemented
      a secure internet-based system to replace the OSOTC's existing fax-based
      procedures. This system meets both the patient evaluation and basic research
      needs of the OSOTC.

PMID- 14728495
TI  - Intelligent intravenous infusion pumps to improve medication administration
      safety.
AB  - Intravenous (IV) medications are vital in the management of hospitalized
      patients. Inpatients frequently receive several IV medications concurrently, and
      these are commonly delivered with infusion pump systems. In particular,
      critically ill patients receive potent "high-alert" IV drugs, many with narrow
      safety margins requiring careful nursing titration. However, while intravenous
      medications have important benefits, errors associated with IV medication
      administration can result in severe or life-threatening adverse drug events
      (ADEs). Although errors in prescribing are often intercepted, administration
      errors do not get caught with most current systems While several safety
      improvements in IV infusion pump design have reduced mechanical complications,
      errors with IV drug administration such as incorrect programming persist.
      Intelligent IV infusion pumps have integrated software to provide point of care
      decision support (DS). This software includes drug library profiles configured
      for specific patient care units and includes programming of safety limits for
      drug/dose calculations.

PMID- 14728496
TI  - XML syntax for clinical laboratory procedure manuals.
AB  - We have developed a document type description (DTD) in Extensable Markup Language
      (XML) for clinical laboratory procedures. Our XML syntax can adequately structure
      a variety of procedure types across different laboratories and is compatible with
      current procedure standards. The combination of this format with an XML content
      management system and appropriate style sheets will allow efficient procedure
      maintenance, distributed access, customized display and effective searching
      across a large body of test information.

PMID- 14728497
TI  - Localization and characterization of mouse-human alignments within the human
      genome. Does evolutionary conservation suggest functional importance?
AB  - In an attempt to validate the use of evolutionary conservation as a method to
      identify putative regulatory elements, we have quantified the frequency of Single
      Nucleotide Polymorphisms (SNPs) within the most tightly conserved regions across
      the entire Human Genome. Our results show that conserved non-coding sequences
      have a significantly lower SNP frequency than their exonic counterparts, which
      suggests that these regions are functionally important.

PMID- 14728498
TI  - Preoperative information management system using wireless PDAs.
AB  - Personal Digital Assistant (PDA) and wireless communication are currently
      available in clinical settings. We developed wireless PDA software that assists
      anesthesiologists in pre-operative patient assessment. The device communicates
      with the hospital information system through a wireless LAN and is equipped with
      pre-programmed data entry templates for pre-operative assessment. As a
      preliminary test of the device, we randomly assigned residents in preoperative
      assessment to an intervention and a control arm and compared the results.

PMID- 14728499
TI  - Smaller and faster: using a handheld computer to support a bedside vascular
      access team.
AB  - An application for a handheld computer was developed to support the Vascular
      Access team in an academic medical center. The development involved workflow
      analysis and usability testing centered on the users. The application interfaced
      with the desktop to generate the documentation needed for the charts and to
      populate the database used to track productivity, volume, outcomes, etc. Post
      implementation evaluations provided feedback to validate the utility of the
      system to support workflow of the team.

PMID- 14728500
TI  - CodeDoc for real-time point-of-care emergencies.
AB  - Can documentation and synthesis of that data be done in time to positively impact
      immediate care, improve documentation, decrease time, error, and improve outcome?
      This poster presents the results of a pilot study that begins to address this
      question. METHOD: A Cross-over design compares manual 'code blue' documentation
      to CodeDoc's method. RESULTS: CodeDoc cut documentation time almost in half with
      fewer errors. CONCLUSION: CodeDoc may have a critical role in improving emergency
      care.

PMID- 14728501
TI  - Using contextual queries.
AB  - Search engines generally treat search requests in isolation. The results for a
      given query are identical, independent of the user, or the context in which the
      user made the request. An approach is demonstrated that explores implicit
      contexts as obtained from a document the user is reading. The approach inserts
      into an original (web) document functionality to directly activate context driven
      queries that yield related articles obtained from various information sources.

PMID- 14728502
TI  - NICU Notes: A Palm OS and Windows database software product and process to
      facilitate patient care in the newborn intensive care unit.
AB  - This is a database software application for information a neonatologist routinely
      considers in the newborn intensive care unit (NICU). Users enter data at the
      point of care on a handheld device that also encrypts the data. Data management
      follows synchronization via an ODBC DSN to a secure Microsoft Access application.
      User feedback guides software modification over time. The poster illustrates the
      data model, the software user interface, and data management products.

PMID- 14728503
TI  - Applying axiomatic design methodology for guideline revision.
AB  - We are investigating the use of axiomatic design (AD) as a principled approach to
      the revision of guidelines. AD models guidelines in a modular and hierarchical
      manner and captures interactions be-tween modules. To test this approach we
      applied AD to encode segments of three guidelines and their revised versions.
      Guideline encodings for the original versions were modified to incorporate
      changes made in the revised documents. The results indicate that AD is a
      promising approach for guideline modeling.

PMID- 14728504
TI  - Improving quality measurement using multiple data sources.
AB  - We calculated a sample of AHRQ Quality and Patient Safety Indicators for UVa
      hospitalized patients over a 3 year period using diagnoses and procedure codes
      from two different billing systems. Significant differences in results were
      observed suggesting that quality indicators calculated from hospital billing
      sources alone may be understated.

PMID- 14728505
TI  - On Track: a database for evaluating the outpatient clinical experience of
      internal medicine residency training.
AB  - Residents in internal medicine training programs spend an increasing amount of
      time in the outpatient setting, creating the potential for substantial
      variability in educational experiences among residents. We developed a data
      management system (On Track) that combines information on clinical experiences
      collected from an electronic medical record (EMR) and handheld personal data
      assistants (PDA). This information is translated into easily interpretable
      graphics and reports that provide insight into the overall residency curriculum
      as well as the experiences of individual residents.

PMID- 14728506
TI  - Modeling virtual healthcare systems: methods for qualitative case analysis and
      sociometry of institutional infrastructures.
AB  - The objective of this paper is to present a strategy for the qualitative analysis
      of virtual institutional infrastructures serving complex healthcare systems.
      Methodologies considered include case analysis, grounded theory, and sociometry.
      The discussion is illustrated with references to case analyses of diverse
      healthcare systems. Particular attention is focused on ideological values
      expressed in market dynamics and system control structures.

PMID- 14728507
TI  - Interactive visualization and exploration of time-oriented clinical data using a
      distributed temporal-abstraction architecture.
AB  - KNAVE-II is a system for visualization and exploration of large amounts of time
      oriented clinical data and of multiple levels of clinically meaningful
      abstractions derivable from these data. KNAVE-II uses a distributed temporal
      abstraction architecture that integrates a set of knowledge services, each
      interacting with a domain-specific knowledge source, a set of data-access
      services, each interacting with a clinical data source, and a computational
      service for deriving knowledge-based abstractions of the data.

PMID- 14728508
TI  - Organizing the animal hierarchy into a Linnean Taxonomy in SNOMED CT.
AB  - SNOMED Clinical Terms (SNOMED CT) was created from a merger of SNOMED Reference
      Terminology (SNOMED RT)and CTV3 the Read Codes. The animal hierarchy in SNOMED RT
      was organized by common names, such as "Dog" and "Cat". It was later decided to
      convert common names to Linnean Taxonomy in SNOMED CT, such as Canis familiaris
      and Felis Sylvestris,in accordance with the Integrated Taxonomic Information
      System (ITIS) and the Smithsonian mammalian taxonomy.

PMID- 14728509
TI  - Decision support systems to identify different species of malarial parasites.
AB  - In this project, medical expert systems were designed to aid technicians,
      students and scientists in identifying various species of malarial parasite from
      blood smears. The rule based system was found to intelligently ask pertinent
      questions to accurately and efficiently identify the species of malarial
      parasite. The probabilistic system provided quantitative feedback as to the
      likelihood of a diagnosis of a species of malaria. Medical expert systems can
      potentially streamline the process of malarial species identification, and can
      aid in training new technicians and scientists in this important skill.

PMID- 14728510
TI  - A knowledge-acquisition wizard to encode guidelines.
AB  - An important step in building guideline-based clinical care systems is encoding
      guidelines. Protege-2000, developed in our laboratory, is a general-purpose
      knowledge-acquisition tool that facilitates domain experts and developers to
      record, browse and maintain domain knowledge in knowledge bases. In this poster
      we illustrate a knowledge-acquisition wizard that we built around Protege-2000.
      The wizard provides an environment that is more intuitive to domain specialists
      to enter knowledge, and domain specialists and practitioners to review the
      knowledge entered.

PMID- 14728511
TI  - Evaluating the Health SmartLibrary.
AB  - The Health SmartLibrary (HSL), supported by the National Library of Medicine
      (Information Systems grant # 1 G08 LM07051-01A1), is a web-based system designed
      to target resources relevant to the users' information needs. Faculty and
      librarians collaborated to build tools that would make access to information
      resources easy and efficient. These tools include current awareness; a metasearch
      engine; a file cabinet; personalization features; and discipline-based resource
      collections.

PMID- 14728512
TI  - The C.A.Ve. software tool for genome assembly.
AB  - Misassembly due to the presence of repetitive DNA sequences often complicates the
      contig assembly stage of genome sequencing. Accurate physical representations of
      chromosomes, such as restriction maps or contig maps, provide a means for
      validating the sequence assembly and clarifying alignment ambiguity. The Contig
      Assembly Verifier (CAVe) software tool allows the researcher to automatically
      reconcile a sequence assembly with a physical representation, and, if needed, to
      modify the assembly using an intuitive graphical user interface.

PMID- 14728513
TI  - Comprehensive functional specifications and design for IT support of clinical
      research at an academic medical center.
AB  - We present a framework for understanding and developing an Information Technology
      (IT) infrastructure for human subject research. First, we review the process of
      clinical research in an academic medical center. Next,we describe the
      entities,roles,and functional relationships within the clinical research
      enterprise to define a conceptual data model. Finally, we address design and
      implementation issues for an IT infrastructure that can be adapted to the local
      needs of research institutions.

PMID- 14728514
TI  - The Open Terminology Services (OTS) project.
AB  - The Open Terminology Services (OTS) project provides a common, well-specified
      mechanism to access terminological content in a vendor and platform neutral
      fashion. The project includes a freely available API specification and an open
      source reference implementation. The API specification derives from the OMG
      Lexicon Query Services interface specification as a foundation and defines
      mechanisms for browsing, querying and import terminological content. The Java
      based reference implementation uses the Lightweight Directory Access Protocol
      (LDAP) for a back end, and provides a mechanism to query and distribute
      heterogeneous terminological content using a common format. The project includes
      the CTS (Central Terminology Services) subset under HL7.

PMID- 14728515
TI  - GELLO: an object-oriented query and expression language for clinical decision
      support.
AB  - GELLO is a purpose-specific, object-oriented (OO) query and expression language.
      GELLO is the result of a concerted effort of the Decision Systems Group (DSG)
      working with the HL7 Clinical Decision Support Technical Committee (CDSTC) to
      provide the HL7 community with a common format for data encoding and
      manipulation. GELLO will soon be submitted for ballot to the HL7 CDSTC for
      consideration as a standard.

PMID- 14728516
TI  - The Minnesota Virtual Clinic: using a simulated EMR to teach medical students
      basic science and clinical concepts.
AB  - The Minnesota Virtual Clinic is a web-based educational tool using a simulated
      EMR to expose students to critical basic science and clinical concepts in the
      context of patient care. The clinic enrolls a group of simulated patients
      representing a variety of conditions and cultural backgrounds and follows them
      over time. Students "attend" the clinic weekly to review the latest developments
      for its patients. The underlying tools facilitate a variety of educational links
      for any item of information from simple popup windows for definitions to
      illustrative images and interactive student exercises. At the same time it
      provides and introduction to certain informatics practices including basic
      security and use of an EMR for patient care.

PMID- 14728517
TI  - A patient-record supporting treatment cost determination.
AB  - The aim of this project was the development of a simple Patient Record Tool,
      supporting health-care professionals to assign appropriate disease codes, related
      to financial and billing data, indispensable for an approximation of the mean
      treatment cost.

PMID- 14728518
TI  - Development of an information model for solid organ transplantation.
AB  - Information required to manage transplant patients and donors is complex,
      voluminous and requires the reporting and use of one person's medical information
      within another person's record. One strategy using a vocabulary model (i.e.,
      LOINC codes with *DONOR specified in the system axes) will lead to problems with
      combinatorial explosion. After evaluating workflow processes, data collection
      forms, decision support and functional requirements, we designed and implemented
      an extendable information model to support the process of care following liver
      transplantation.

PMID- 14728519
TI  - Quantifying visual similarity in clinical iconic graphics.
AB  - Numerous studies have demonstrated the benefits of utilizing iconic presentation
      models in the context of complex medical information. However, very little
      literature exists that addresses the design of the graphical primitives that
      constitute such mediums. Utilizing a method named "Presentation Discovery", the
      authors of this study examine a manner in which objective techniques may be
      utilized to prototype such graphical primitives in order to increase the realized
      expressiveness of ensuing iconic presentation models.

PMID- 14728520
TI  - Encoded guidelines for targeted latent tuberculosis screening using an electronic
      medical record.
AB  - To determine the impact of information technology on embedding the latent
      tuberculosis infection (LTBI) screening guidelines in an electronic medical
      record (EMR) in a large health care system. The long-term goal of the study is to
      test clinician adherence to LTBI screening guidelines using an EMR system.
      However, preliminary results are presented on the potential impact on providers
      on implementing the alerts on targeted high-risk patients.

PMID- 14728521
TI  - Comparison of three methods of entering clinical information into a prototype
      triage system.
AB  - This research study is a prospective, randomized trial evaluating varied means of
      inputting structured clinical data into a prototype triage system. Three
      different methods of historical data entry were evaluated for efficiency, quality
      of obtained data and ease of use. The results show that using a "customized" form
      containing check-box entries for only the most commonly seen historical data and
      space for text entry of other information was the most accurate method of
      entering triage information and was nearly as fast and easy as free text entry.

PMID- 14728522
TI  - Feasibility of using a large Clinical Data Warehouse to automate the selection of
      diagnostic cohorts.
AB  - Data from Clinical Data Warehouses (CDWs) can be used for retrospective studies
      and for benchmarking. However, automated identification of cases from large
      datasets containing data items in free text fields is challenging. We developed
      an algorithm for categorizing pediatric patients presenting with respiratory
      distress into Bronchiolitis, Bacterial pneumonia and Asthma using clinical
      variables from a CDW. A feasibility study of this approach indicates that case
      selection may be automated.

PMID- 14728523
TI  - Prescription of amiodarone through a computerized template that includes both
      decision support and executive functions improves the monitoring for toxicities.
AB  - The antiarrhythmic drug amiodarone causes severe side effects that warrant active
      monitoring. In a given patient, monitoring for amiodarone toxicities involves
      checking past results of five laboratory/imaging tests and reordering four of
      these tests every 6 to 12 month, a process that is both complex and time
      consuming. We hypothesized that a software tool that automated the retrieval and
      ordering of these tests in a context-sensitive manner would improve the
      completeness of surveillance for drug toxicities.

PMID- 14728524
TI  - A novel way of distributing medical practice guidelines using Personal Digital
      Assistants (PDA).
AB  - With the rapid growth in medical knowledge, physicians' ability to keep up to
      date has become increasingly difficult. Although the Internet brought significant
      improvements in access to medical knowledge, there are still problems remaining,
      particularly for the mobile physician who is unable to perform time-consuming on
      line searches, even with wireless access to the Internet. The goal of this
      project was to develop a novel way of distributing medical knowledge from the
      Internet to health professionals' Personal Digital Assistants (PDAs). This model
      delivers targeted information and provides access to that information at the
      point of care.

PMID- 14728525
TI  - How easy/difficult to find information about individual health insurance on the
      Internet: an examination of ten "quote" web sites.
AB  - Ten quote web sites were evaluated to examine the level of difficulty in finding
      information about individual health insurance. The degrees of ease/difficulty
      were measured in terms of the number of items to be filled out on the form in
      order to get a quote. Also examined were whether the quote web sites revealed
      their identity and whether they provided information about the health plans they
      quoted. The results showed that some quote web sites did not reveal information
      about themselves fully. The degrees of ease or difficulty varied from site to
      site. Not all quote web sites could provide quotes instantly. Among those that
      provided a quote, the amount of information given on the health plans also
      varied. Despite the difficulties, the internet has the potential to provide
      sufficient information.

PMID- 14728526
TI  - Epi info - present and future.
AB  - Epi Info is a suite of public domain computer programs for public health
      professionals developed by the Centers for Disease Control and Prevention (CDC).
      Epi Info is used for rapid questionnaire design, data entry and validation, data
      analysis including mapping and graphing, and creation of reports. Epi Info was
      originally created in 1985 using Turbo Pascal. In 1998, the last version of Epi
      Info for DOS, version 6, was released. Epi Info for DOS is currently supported by
      CDC but is no longer updated. The current version, Epi Info 2002, is Windows
      based software developed using Microsoft Visual Basic. Approximately 300,000
      downloads of Epi Info software occurred in 2002 from approximately 130 countries.
      These numbers make Epi Info probably one of the most widely distributed and used
      public domain programs in the world. The DOS version of Epi Info was translated
      into 13 languages, and efforts are underway to translate the Windows version into
      other major languages. Versions already exist for Spanish, French, Portuguese,
      Chinese, Japanese, and Arabic.

PMID- 14728527
TI  - Visualizing AMIA : a medical informatics knowledge domain analysis.
AB  - Medical Informatics has been described as having a "long and delayed adolescence"
      which continues to "find itself in search of self-definition", and the AMIA
      Symposium Proceedings have been viewed as an indicator of trends in the field.
      This pilot study investigated the feasibility of applying a knowledge domain
      visualization approach to clarifying the domain of medical informatics based on
      the AMIA publications. Document co-citation analysis (DCA) is combined with
      Pathfinder Network Scaling (PFNET), visualization, and animation to develop a 3-D
      knowledge landscape.

PMID- 14728528
TI  - Developing a methodology to improve the allocation of specialized health
      resources for acutely injured persons.
AB  - Inappropriate triage following acute injury may result in misallocation of
      specialized health resources, increased health care costs, reduced or delayed
      access to care, and increased death and disability. Although triage criteria have
      been developed, they vary widely, and inappropriate triage rates are high (50% -
      85%). The purpose of this project was to evaluate the ability of decision tree
      induction to predict need for specialized trauma resources in acutely injured
      persons. We considered any person who was admitted to the trauma center's ICU or
      died prior to being admitted to the ICU as needing specialized trauma resources.

PMID- 14728529
TI  - Implementing a personalized portal combined with workflow management tools used
      in diabetes care.
AB  - Diabetes care is one of the most important medical care works in nowadays.
      However, the dispersal of current diabetes medical practice leads to an
      uncoordinated work flow. Lacking of personal health information makes patients
      hard to implement self-care and medical providers have to deal with lots of
      paperwork. Information technology has mobile characters to assist medical
      providers collecting and managing patient data conveniently. Using customized and
      accessible web technology to promote patient abilities of self-care as well as to
      help care providers plan patient-oriented care. Automatic workflow applied to
      care guidelines could reduce workload and improve work efficiency of care
      provider. Make the most out of information technology to build an integrated
      "Diabetes Care System". Thus we can provide complete disease management service
      which should be the most useful solution to meet the challenges of conventional
      care.

PMID- 14728530
TI  - Transition from in library use of resources to outside library use: the impact of
      the Internet on information seeking behavior of medical students and faculty.
AB  - Advances in information technology have introduced both new capabilities and
      interesting challenges in accessing medical literature. More and more information
      resources exist in electronic format, such as online databases, journals, books,
      etc. instead of the traditional print format. In late 1998, there were thirty
      five journal titles available online; in 2001, the number rose to over 4,000.1
      Desk-top access to online resources is changing library use patterns, which
      challenges libraries to adjust to this transformed information access
      environment. Studies of the impact of the internet on information seeking
      behavior of users in medical environments could provide very valuable information
      for medical libraries seeking to adapt to this rapid and great evolution. This
      study aims to explore the impact of the Internet on information seeking behavior
      of medical students and faculty and their medical library use, to address the
      possible reasons for this change of information seeking behavior, and to identify
      the measures essential to the transition from traditional in-library use of
      resources to remote access. This study is conducted in two phases.

PMID- 14728531
TI  - A "systematics" tool for medical terminologies.
AB  - Finding the hierarchical relations amongst multiple terms within medical
      terminologies that support multiple parents to a term is a common task,
      especially for trainees and knowledge engineers implementing or maintaining
      medical logic modules or guidelines. Examples of such terminologies include the
      UMLS and the Medical Entity Dictionary (MED). In addition, the task of
      identifying and discriminating amongst some common ancestors to a list of terms
      is a recurrent theme. This is also a common concern in the science of
      classification (systematics). Some nearest common ancestors have distinct
      valuable properties for classification and simplification of lists. Although
      there exist some visualized navigating and editing tools for the UMLS and the
      MED, they are browsers that show a large number of unrelated and irrelevant
      relationships to the task at hand. While algorithms have been well studied in
      computer science to solve such a problem over semantic networks and trees, to our
      knowledge, they have not been used with a visualization tool in biomedicine. We
      developed a visualized tool that graphically displays the hierarchical relations
      of multiple terms, and helps identifying the nearest common ancestors of these
      terms.

PMID- 14728532
TI  - Implementing a MIRC interface for a database driven teaching file.
AB  - This poster describes the feasibility of integrating an existing database driven
      teaching file with the Radiological Society of North America's (RSNA) Medical
      Imaging Resource Center (MIRC). MIRC is the product of an RSNA sponsored
      initiative to enable medical institutions to share their electronic medical
      content (images, text, and multimedia) by creating a distributed repository
      accessible from the Internet. A description of MIRC's query/storage service
      architecture is provided along with an overview of the author's experience with
      implementing a storage service front end for an existing, database driven
      teaching file system.

PMID- 14728533
TI  - A validated logistic regression model to identify coronary heart disease patients
      within primary care databases in the United kingdom.
AB  - We established the optimal search strategy for identifying coronary heart disease
      (CHD) patients within the Electronic Patient Record (EPR) of 'paperless' family
      practices in the UK. Multiple logistic regression modelling (MLRM) and Receiver
      Operating Characteristic (ROC) curves were used to develop the query. The
      selected search strategy was validated at 2 additional paperless family
      practices.

PMID- 14728534
TI  - The characteristics of personal order sets in a computerized physician order
      entry system at a community hospital.
AB  - Personal order sets (POS) have been touted as important for the success of a
      computerized physician order entry (CPOE) system. However, POS may systematize
      practice variability and are difficult to centrally administer. Few studies have
      looked at the characteristics and use of POS in a community hospital. We examined
      how POS are used at the Queen's Medical Center (QMC). POS are an important part
      of the success of the QMC CPOE, but have definite disadvantages.

PMID- 14728535
TI  - Extension of Air Transport Minimum Data Set to fixed-wing environment.
AB  - The Air Transport Minimum Data Set (ATMDS) was developed to address data needs
      for rotor wing transport of critically ill or injured patients. Using a focus
      group methodology, nurses, paramedics, pilots, and communications specialists
      identified additional concepts such as time arrived at airport via ground
      transportation to represent the complexity present in fixed wing transport.
      Specific concepts, selected terms for the concepts and definitions will be
      discussed.

PMID- 14728536
TI  - A probabilistic similarity metric for Medline records: a model for author name
      disambiguation.
AB  - We present a model for automatically generating training sets and estimating the
      probability that a pair of Medline records sharing a last and first name initial
      are authored by the same individual, based on shared title words, journal name,
      co-authors, medical subject headings, language, and affiliation, as well as
      distinctive features of the name itself (i.e., presence of middle initial,
      suffix, and prevalence in Medline).

PMID- 14728537
TI  - A clinically rooted approach to Knowledge Management in a large Italian community
      hospital.
AB  - A strategy for Knowledge Management (KM) implementation in a large hospital
      involved three areas: intranet/internet technologies for professional practice
      standardization and communication; multiprofessional group building for sharing
      and discovering of social perspectives; learning opportunities targeted to high
      quality information sources and information mastering methods. A cooperative
      prototyping approach assured high levels of user's acceptance and involvement,
      and initial results are encouraging, but measuring and sustaining clinical
      practice changes will require additional efforts.

PMID- 14728538
TI  - An email alert system for internal medicine physicians.
AB  - This study evaluated the effectiveness of an email-based alerting system for
      internal medicine house staff and faculty in geographically dispersed locales.
      Responses to a test alert email message were used to quantify the rapidity by
      which physicians read the message, and to define subgroups in which this
      communication modality proved most successful. The results of this study are
      being used to improve our preparedness for emergencies.

PMID- 14728539
TI  - Provider Link: facilitating healthcare providers' support of web-based smoking
      cessation efforts via secure e-mail.
AB  - Provider Link is a system designed to enhance the efficacy of a web-based
      intervention for smoking cessation by helping health care providers support their
      patients via e-mail. The system is designed to maintain confidentiality while
      allowing providers rapid access to patient data collected over the web. A trial
      of Provider Link is currently underway.

PMID- 14728540
TI  - Scheduling software in public health practice: from book to bytes and back.
AB  - Although greater emphasis is being placed on public health information transfer,
      little is known about its implementation in the field. To better understand the
      information needs of the public health workforce, semi-structured interviews were
      conducted at a country public health department. Preliminary investigation
      revealed the underutilization of available scheduling software in this setting.
      Privacy concerns and idiosyncratic scheduling patterns may have interfered with
      the adoption of commercially available scheduling software.

PMID- 14728541
TI  - Metcalfe's law predicts reduced power of Electronic Medical Record software.
AB  - Error reduction, quality improvement and lowering of cost can all be achieved
      through electronic integration of health care providers. Despite the existence of
      clinical computing software for decades, meaningful linkage between health care
      providers has not occurred. We hypothesize that a major reason is reduction in
      network value through incompatible clinical software among hundreds of health
      care entities.

PMID- 14728542
TI  - SNOMED CT encoded Cancer Protocols.
AB  - SNOMED Clinical Terms (SNOMED CT) is being used to encode the Cancer Protocols
      published by the College of American Pathologists (CAP). As of January 1, 2004,
      one of the standards set for approved cancer programs by the American College of
      Surgeons Commission on Cancer will be that at least 90% of surgical pathology
      reports contain all essential data elements identified in the CAP Cancer
      Protocols.

PMID- 14728543
TI  - Cholgate - a randomized controlled trial comparing the effect of automated and on
      demand decision support on the management of cardiovascular disease factors in
      primary care.
AB  - Automated and on-demand decision support systems integrated into an electronic
      medical record have proven to be an effective implementation strategy for
      guidelines. Cholgate is a randomized controlled trial comparing the effect of
      automated and on-demand decision support on the management of cardiovascular
      disease factors in primary care.

PMID- 14728544
TI  - Rigorously assessing whether the data backs the back school.
AB  - A rigorous between-subjects methodology employing independent random samples and
      having broad clinical applicability was designed and implemented to evaluate the
      effectiveness of back safety and patient transfer training interventions for both
      hospital nurses and nursing assistants. Effects upon self-efficacy, cognitive,
      and affective measures are assessed for each of three back safety procedures. The
      design solves the problem of obtaining randomly assigned independent controls
      where all experimental subjects must participate in the training interventions.

PMID- 14728545
TI  - Applying Knowledge Discovery in Databases in public health data set: challenges
      and concerns.
AB  - We are investigating the use of axiomatic design (AD) as a principled approach to
      the revision of guidelines. AD models guidelines in a modular and hierarchical
      manner and captures interactions be-tween modules. To test this approach we
      applied AD to encode segments of three guidelines and their revised versions.
      Guideline encodings for the original versions were modified to incorporate
      changes made in the revised documents. The results indicate that AD is a
      promising approach for guideline modeling.

PMID- 14728546
TI  - Clinical research databases: getting from current state to best practice.
AB  - Clinical research databases reside at the foundation of health sciences, yet
      experts outside of information science often manage research data. Improper data
      management presents risks to the researcher, research community, research
      subjects, and other patients. Data management must aim to preserve or maximize
      the value of data. We created a checklist tool for researchers and/or data
      administrators to use when evaluating their database operations. The tool
      addresses both liabilities and the value of the data.

PMID- 14728547
TI  - Patient Online at Dartmouth-Hitchcock - interactive patient care web site.
AB  - This poster presentation will demonstrate the value to practices of providing
      online interactive communication tools to their patients by presenting Dartmouth
      Hitchcock's successful implementation of "Patient Online". This tool extends our
      clinical and administrative functions directly to patients using a personal web
      site product that supports HIPAA compliant clinical communication, patient
      appointment scheduling, prescription renewals, and referral requests with the
      practice.

PMID- 14728548
TI  - Development of a biomedical imaging informatics system for diagnosis and
      treatment planning.
AB  - The medical imaging technologies have been used for detecting tumors through the
      years. Tumors that can be viewed in imaging are usually big enough to contain
      billion tumor cells. Some patients may be cured if detected earlier and the
      surgery is performed well. Those lead to molecular imaging and image-guided
      surgery research activities, which post new challenges on large scale imaging
      data management and 3-D visualization. The goal of this project is to develop 3-D
      imaging informatics system that can interactively navigate large scale of organ
      and molecular levels imaging data for early diagnosis and treatment planning.

PMID- 14728549
TI  - HIV terms coverage by a commercial nomenclature.
AB  - A formal comparison of physician notes on HIV patients with MEDCIN was carried
      out. Terms from patient charts were divided into five groups: History, Physical
      Examination, Symptoms, Diagnosis and Doctor's Orders. Four types of matches were
      determined: Exact, Lexical, Semantic and No-Match. Across the five groups, exact
      matches ranged from 12 to 44 percent, lexical matches from 2 to 11 percent,
      semantic matches from 9 to 21 percent, and no-matches from 29 to 74 percent.

PMID- 14728550
TI  - Where is the nursing in SNOMED CT? CTGFN has the answer!
AB  - The SNOMED" micro CTGFN (Convergent Terminology Group for Nursing) is a working
      group reporting to the SNOMED International Editorial Board. They are charged
      with ensuring a terminology supportive of nursing's requirement for describing
      patient care. The strategies utilized for nursing content follow.

PMID- 14728551
TI  - Common data element (CDE) management and deployment in clinical trials.
AB  - The NCI provides the cancer Data Standards Repository (caDSR) to support
      development and deployment of CDEs in cancer research. The caDSR, part of the NCI
      caCORE infrastructure, supports data management workflow requirements and
      adherence to ISO/IEC 11179 metadata standards. CDEs are developed using standard
      terminology from caCORE vocabulary services, and are then deployed to multi-site
      clinical trials data management systems. Here we describe the caDSR and how CDEs
      are managed and deployed in clinical research.

PMID- 14728552
TI  - Formative evaluation to guide early deployment of an online content management
      tool for medical curriculum.
AB  - KM is a Web-accessible, comprehensive database that organizes course materials
      (at the level of full lectures, not just outlines or syllabi) from the Vanderbilt
      School of Medicine curriculum. KM uses natural language processing techniques to
      analyze educational documents for biomedical concepts. Lecture handouts and
      Microsoft PowerPoint presentations are indexed and available online for students,
      faculty and administrators to search for individual or interrelated concepts
      across the medical school curriculum.

PMID- 14728553
TI  - Derivation of malignancy status from ICD-9 codes.
AB  - To assess the severity of illness of oncology patients, it is necessary to
      distinguish patients with a single primary tumor from patients with metastatic
      disease occurring at a secondary location remote from the primary site. We
      developed a ranked list of cancer groupings and an algorithm that could
      distinguish patients with primary and metastatic cancer even if no specific code
      for secondary cancer was recorded. In patients with metastatic disease, the
      algorithm should also distinguish the primary site from the secondary site.

PMID- 14728554
TI  - Scenario-based participatory design of a collaborative clinical trial protocol
      authoring system.
AB  - We present our experience of using prototype scenarios to actively involve users
      in the design of a collaborative clinical trial protocol authoring system. This
      method enables us to do usability testing and elicit prompt user feedback at the
      early phase of de-sign. We conclude that it is an effective approach to the
      design of complex medical information systems.

PMID- 14728555
TI  - Encouraging adolescents toward mental health careers via website biographies.
AB  - This project designed, developed, implemented and is currently evaluating the
      effectiveness of an interactive, multi-media website designed to encourage
      adolescents to consider careers in mental health. This Web-based learning
      environment features biographies of mental health scientists. Evaluation is
      conducted in a systematic, structured way using cognitive achievement, usability
      (ease of use), and affective scales (e.g., fun to use) as outcome measures

PMID- 14728556
TI  - The Israel Penn International Transplant Tumor Registry.
AB  - The Israel Penn International Transplant Tumor Registry is literally the world's
      premier repository of information on patients who have developed malignancies
      after organ transplants. The administrators of the Registry not only collect
      information but also provide consulting services based on the accumulated
      knowledge that the Registry contains. By creating a secure Web-based front end,
      we have made it possible for the Registry to keep pace with its burgeoning
      international caseload.

PMID- 14728557
TI  - A wireless mobile health-related quality of life assessment.
AB  - Self-administered waiting room questionnaires are popular tools for gathering
      health information from patients, but they require optical scanning or manual
      data entry to obtain survey results. The application described here eliminates
      those extra steps by inputting the results into a remote database directly
      through wireless connection, and the assessment can be finished easily anywhere
      in the clinic through a mobile platform. A measure of health-related quality of
      life, the SF-8 Health Survey, was used in developing this application for using
      in the clinical setting. It has only eight questions measuring each of the eight
      domains of health in the longer SF-36 Health Survey.

PMID- 14728558
TI  - Task centered visualization of Electronic Medical Record flow sheet.
AB  - Usability problem of Electronic Medical Record (EMR) systems is a major hurdle
      for their acceptance. In this study we used the methodology of Human-Centered
      Distributed Information Design (HCDID) to compare and evaluate Flow Sheet module
      of two commercial EMR systems. After which we tried to develop usable interface
      of a flow sheet using visualization, focusing on task-representation mapping
      during design and development.

PMID- 14728559
TI  - Mouse models of human cancer web-based resources.
AB  - The Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative program
      designed to derive and characterize mouse models of human malignancies. To
      enhance information and resource exchange among the MMHCC investigators and other
      cancer research scientists, the NCI Center for Bioinformatics (NCICB,
      http://ncicb.nci.nih.gov/) has developed web-based resources that are freely
      available to the cancer research community. These resources include a website
      (http://emice.nci.nih.gov) and databases for cancer models
      (http://cancermodels.nci.nih.gov) and cancer images
      (http://cancerimages.nci.nih.gov).

PMID- 14728560
TI  - Facilitating research in pathology using natural language processing.
AB  - Clinical research projects frequently rely on manual extraction of information
      from pathology reports, which is a costly and time-consuming process. This paper
      describes use of a natural language processing (NLP) system to automatically
      extract and structure information in textual pathology reports that is needed for
      clinical research.

PMID- 14728561
TI  - A local report entry system for governmental collection of medical adverse
      events.
AB  - Japanese government started the governmental collection of medical adverse events
      in October 2001. That provides data entry methods by hospitals, not by
      departmental risk managers. It was the barrier to wide spread. A Local Report
      Entry System was developed, which allowed risk managers to report by their HIS
      terminals with its user-friendly graphical user interface.

PMID- 14728562
TI  - Exploring security and privacy issues in hospital information system: an
      Information Boundary Theory perspective.
AB  - A small community hospital (67 beds) in Central New York was undergoing a major
      technological change within the organization, as they move from the use of
      several legacy information systems to a hospital-wide information system. The
      focus of the present research is to explore the privacy and security information
      issues using a framework called Information Boundary Theory [Stanton, 2002]. IBT
      explains the motivational factors that lead to the revelation or disclosing of
      information.

PMID- 14728563
TI  - MyWelch: building an information portal system in a medical library environment.
AB  - MyWelch is a medical library portal system that users can use to create
      customized web sites that reflect their research needs and personal interests. In
      the MyWelch environment, faculty and students are empowered to take a greater
      role in identifying their needs and determining their requirements in the
      electronic environment. The portal system also facilitates interaction among
      library users and staff.

PMID- 14728564
TI  - The design and implementation of a picklist authoring tool.
AB  - It is well recognized that controlled medical terminologies play a critical role
      in Health Information Systems and Clinical Patient Record systems, but the
      creation and management of customized lists of terms ("picklists") remains a
      potential obstacle. We have been developing a sophisticated authoring tool that
      is fully integrated with our terminology server and that will be made available
      to our system analysts and clinicians.

PMID- 14728565
TI  - UMLF: a Unified Medical Lexicon for French.
AB  - Lexical resources for medical language, such as lists of words with inflectional
      and derivational information, are publicly available for the English lantuate
      with the UMLS Specialist Lexicon. The goal of the UMLF project is to pool and
      unify existing resources and to add extensively to them by exploiting medical
      terminologies and corpora, resulting in a Unified Medical Lexicon for French. We
      present here the current status of the project.

PMID- 14728566
TI  - The multimedia electronic patient record: current issues.
AB  - Complete online patient data including both traditional medical chart information
      and clinical images is essential in providing healthcare in a multi-facility
      environment. To meet this need, the Department of Veterans Affairs has developed
      a multimedia online patient record that includes traditional medical chart
      information as well as a wide variety of medical images from specialties such as
      cardiology, pulmonary and gastrointestinal medicine, pathology, radiology,
      hematology, and nuclear medicine. The ability to perform direct image acquisition
      from DICOM devices combined with diagnostic radiology reading from high
      resolution workstations allows hospitals to operate without making xray film. The
      wide area network connection supports ad hoc queries to records at other VA
      sites. The practicing physician has all of the information needed, anywhere in
      the hospital, at any time.

PMID- 14728567
TI  - HIV/AIDS Community Health Information System.
AB  - Given changes in the faces of AIDS over the last decade, it is crucial that
      disparities in health and access to healthcare are addressed. An Internet-based
      GIS was developed using ESRI's Arc Internet Map Server (Arc IMS) to provide users
      with a suite of tools to interact with geographic data and conduct spatial
      analyses related to the characteristics that promote or impede the provision of
      HIV-related services. Internet Mapping allows those engaged in local decision
      making to: (1) geographically visualize information via the Internet; (2) Assess
      the relationship between the distribution of HIV services and spatially
      referenced socio-economic data; and (3) generate "what if" scenarios" that may
      direct the allocation of healthcare resources.

PMID- 14728568
TI  - Supporting communication in an integrated patient record system.
AB  - Over the past two years, Vanderbilt University Medical Center (VUMC) has
      developed and implemented an integrated user interface front end that gives users
      a homogeneous view that supports directly the clinical workflow. This system,
      known as StarPanel, is a Web-based front end that integrates seamlessly all the
      functions needed for busy outpatient clinics. The key design concept is the
      ability to support communication as the fundamental activity of a health care
      team.

PMID- 14728569
TI  - The NCI/CIT microArray database (mAdb) system - bioinformatics for the management
      and analysis of Affymetrix and spotted gene expression microarrays.
AB  - A scalable, modular, enterprise-level system for both microarray databasing and
      analysis over the Internet has been developed over the past four years by the
      National Cancer Institute's Center for Cancer Research in collaboration with
      NIH's Center for Information Technology. This completely Web-based system, called
      mAdb (for microArray database), is currently supporting over 810 registered users
      and collaborators at NIH and contains over 22,000 microarray experiments, making
      it one of the largest collections of microarray data in existence. In addition,
      the mAdb system has been ported for the Netherlands Cancer Institute, the Genome
      Institute of Singapore, and the CDC. This system has been used for a wide variety
      of scientific experiments spanning the range from cancer to studies of early
      development, and for human, mouse, rat, yeast, and numerous microbial organisms.

PMID- 14728570
TI  - eGrants: University of Cincinnati's Digital grants preparation, workflow routing,
      and submission system.
AB  - Overabundance of largely unorganized and unfiltered information is the greatest
      information problem facing the faculty, staff, and students of the University of
      Cincinnati (UC). The goal of UC's IAIMS operations grant is to provide
      individuals with information that is organized, filtered, context -appropriate,
      and presented in personalized formats. This presentation will focus on one
      module, eGrants, of UC's IAIMS research administration system,which will fully
      digitize the pre-award, post-award, and compliance phases of the grant lifecycle
      . eGrants will streamline and reduce errors in the grant preparation, routing,
      and submittal process thus raising the overall quality of and consistency of
      grant submittals and greatly reducing the time and the cost of grant preparation.

PMID- 14728571
TI  - The Military Health System Computer-based Patient Record.
AB  - The Composite Health Care System II (CHCS II) is the Military's electronic
      Computer-based Patient Record, a clinical information system that will generate,
      maintain, and provide secure online access to a comprehensive and legible health
      record. In moving to CHCS II, the Department of Defense (DoD) is making the
      quantum leap from paper based medical records to computer based patient record
      (CPR). The CPR will enable DoD health care to meet its strategic goals for the
      21st century and is paramount to providing comprehensive patient-focused
      information.

PMID- 14728572
TI  - Development and successful pilot of a web-based scaleable, distributed curriculum
      development and management system for medical education.
AB  - In response to a need for a comprehensive online curriculum development and
      management system for medical education at the University of Pittsburgh the
      author, the Lab for Educational Technology (the Lab), students and faculty
      developed the Pitt Med Navigator website (Navigator). This completely web-based,
      distributed, personalized application is used by students and faculty to: 1)
      create, manage, and rapidly access online course resources; 2) author teaching
      cases, interactive multimedia presentations, and quizzes; and 3) manage a
      personal education portal. Four pilot courses and objective evaluations have
      revealed high student and faculty utilization and a high degree of perceived
      educational value.

PMID- 14728573
TI  - Improving HIV/AIDS services through a network-based health information system.
AB  - RW CAREWare is a free Microsoft Accessa-based application developed and
      distributed by the HIV/AIDS Bureau (HAB) in the Health Resources and Services
      Administration of the US Dept. of Health and Human Services. This presentation
      will demonstrate the main screens and functions of CAREWare, including the
      ability to generate a number of service and clinical outcome reports; produce
      lists of clients requiring specific follow-up for care and treatment; create
      custom fields; and produce longitudinal graphs of laboratory tests and medication
      regimens. The security features, data-sharing arrangements among network members,
      and flexibility of the.NET version will also be emphasized.

PMID- 14728574
TI  - BioSTORM: a system for automated surveillance of diverse data sources.
AB  - Heightened concerns about bioterrorism are forcing changes to the traditional
      biosurveillance-model. Public health departments are under pressure to follow
      multiple, non-specific, pre-diagnostic indicators, often drawn from many data
      sources. As a result, there is a need for biosurveillance systems that can use a
      variety of analysis techniques to rapidly integrate and process multiple diverse
      data feeds using a variety of problem solving techniques to give timely analysis.
      To meet these requirements, we are developing a new system called BioSTORM
      (Biological Spatio-Temporal Outbreak Reasoning Module).

PMID- 14728575
TI  - Supporting patient care beyond the clinical encounter: three informatics
      innovations from partners health care.
AB  - As the focus of medicine moves from acute episodic care in the hospital to
      chronic disease management in outpatients, the primary care physician will play
      an increasingly important role in the coordination of patient care activities.
      Traditional outpatient informatics systems have largely focused on the workflow
      during the clinical encounter. Many tasks, including management of test
      results,coordination of subspecialty referrals and communication between patients
      and the practice,remain unsupported. When these tasks are not performed well,
      quality of care, patient safety and satisfaction may suffer. To address these
      issues ,Partners Healthcare in Boston, MA has recently developed several
      applications to address these issues. This demonstration will showcase 3 of these
      new applications: i) Results Manager, ii) Referrals Manager and iii) Patient
      Gateway. All interoperate with a browser-based electronic medical record already
      used by over 500 primary care physicians at Partners Healthcare.

PMID- 14728576
TI  - A Web-Based system for interactive visualization and exploration of time-oriented
      clinical data and their abstractions.
AB  - In this theater-style demonstration, the speakers will demonstrate KNAVE-II, a
      Web-based distributed system for interactive visualization and exploration of
      large amounts of time-oriented clinical data from multiple sources, and of
      clinically meaningful concepts (abstractions) derivable from these data. The
      KNAVE-II system and its complete underlying architecture provide a solution to
      the data overload problem.

PMID- 14728577
TI  - Quill: a novel approach to structured reporting.
AB  - The authors will demonstrate Quill (QUestions and Information Logically Linked),
      a comprehensive structured reporting environment for ambulatory care that was
      developed at the Vanderbilt University Medical Center. A notes capture tool was
      sought with the immediate hope of decreasing or eliminating transcription costs
      (currently around $6M/yr) and paper based processing while providing a foundation
      for decision support and research in the future.

PMID- 14728578
TI  - Computer games may be good for your health: shifting healthcare behavior via
      interactive drama videogames.
AB  - There is increasing evidence that interactive learning systems have an important
      role in reducing health risks and improving general health status. This theater
      style demonstration is aimed at harnessing people's passions for videogames and
      the movies, and a major purpose of this research is to explore alternative ways
      for a game generator to help authors to introduce entertainment and free play as
      well as learning by teaching into role playing games and interactive dramas that
      are behavioral interventions in disguise.

PMID- 14728579
TI  - The Trial Bank system: capturing randomized trials for evidence-based medicine.
AB  - Randomized controlled trials (RCTs) are one of the best sources of evidence for
      the scientific practice of medicine. However, RCT findings are published only as
      text articles that are of limited machine understandability. The Trial Bank
      system captures information about the design, execution, and summary results of
      RCTs into a structured electronic knowledge base called RCT Bank.

PMID- 14728580
TI  - XNBC V9: a simulation package of biological neural networks for the
      neurobiologist, easy to use, full featured and extensible.
AB  - XNBC is intended to simulate biological neural networks. XNBC V9 is an important
      evolution of the previous versions of the XNBC package, a full featured
      application for computer naive neuroscientists. XNBC is controlled via a user
      friendly interface based on XWindow, Motif (Lesstif) and GTK and produces native
      colour PostScript high quality graphic outputs. XNBC is a public domain software
      package, distributed as an open source under the GNU GPL licence, easily
      installable using the classical configure/make/make install.

PMID- 14728581
TI  - Enhancing Computerized Provider Order Entry (CPOE) for neonatal intensive care.
AB  - The authors describe design, implementation, and use of a new order entry system
      module for neonatal intensive care. WizOrder is a Computerized Provider Order
      Entry (CPOE) system developed at Vanderbilt University Medical Center. Since
      WizOrder's introduction in 1995, it has been continually refined and enhanced;
      especially when new hospital units and specialties are implemented. Recently, in
      March 2003, WizOrder was updated and implemented in the Neonatal Intensive Care
      Unit (NICU).

PMID- 14728582
TI  - Rapid deployment of physician order entry using web-based, disease-specific order
      sets.
AB  - Computerized physician order entry (POE) is a disruptive technology that holds
      great promise to reduce medical errors and improve workflow. However, Studies
      have reported significant physician resistance. This presentation will describe a
      two-pronged strategy to build broad support for POE: To build a secure, open
      source, browser-based platform to support POE and create a large number of
      disease-specific order-sets for immediate use. This presentation will demonstrate
      the conceptual framework and implementation requirements for such an endeavor.

PMID- 14728583
TI  - MEDIANOVO - a media database for medical education, research and health care.
AB  - MEDIANOVO provides a high quality, scientifically indexed multi-media database
      with comfortable authoring and download functions through a web-based frontend.
      Currently, MEDIANOVO is used by medical teachers as a repository for storing and
      sharing media for educational purposes. However a database was created which
      could also serve with training and further education, in computer based learning
      systems as well as medical publishers and for individual patient information.
      Through the web-frontend the content is available worldwide.

PMID- 14728584
TI  - Herbal medicine: current status and the future.
AB  - The number of patients seeking alternate and herbal therapy is growing
      exponentially. Herbal medicines are the synthesis of therapeutic experiences of
      generations of practicing physicians of indigenous systems of medicine for over
      hundreds of years. Herbal medicines are now in great demand in the developing
      world for primary health care not because they are inexpensive but also for
      better cultural acceptability, better compatibility with the human body and
      minimal side effects. However, recent findings indicate that all herbal medicines
      may not be safe as severe consequences are reported for some herbal drugs. Most
      herbal products on the market today have not been subjected to drug approval
      process to demonstrate their safety and effectiveness. Thousand years of
      traditional use can provide us with valuable guidelines to the selection,
      preparation and application of herbal formulation. To be accepted as viable
      alternative to modern medicine, the same vigorous method of scientific and
      clinical validation must be applied to prove the safety and effectiveness of a
      therapeutical product. In the present review we attempted to describe the present
      scenario and project the future of herbal medicine.

PMID- 14728585
TI  - Gastro-intestinal cancer in Indonesia.
AB  - BACKGROUND: Report on cancer incidence in Indonesia was presented in relative
      frequency. To lower the bias, the report has been presented in age standardized
      cancer ratio (ASCAR). The report was a department of pathology based cancer
      registration. The ASCAR of gastro intestinal cancer in Indonesia has some
      variation between pathologic centres. The incidence of rectal cancer in
      Jogjakarta was higher than colon cancer, and stomach cancer is very low. The risk
      factors of stomach cancer are H. Pylori infection and food consumption especially
      salt and the risk factor of colorectal cancer is food consumption. PURPOSE: The
      article will discuss the ASCAR of stomach and colorectal cancer in Indonesia. The
      histopathologic of stomach and colorectal cancer in Jogjakarta will be presented
      from the view point of pathology. METHODS: Stomach and colorectal cancer data
      from 13 pathologic diagnostic centres in Indonesia were collected. The
      pathogenesis of stomach and colorectal cancer will be discussed in correlation
      with the cancer prevention. RESULTS: The incidence of stomach cancer in many
      centres in the year of 1996 are very low from 0,00% - 0,24 % for the most lowest
      incidence and 2.22 % - 5.60 % for the highest incidence. The higher incidence of
      stomach cancer was in Medan 19 males (5.6%); 10 females (2.22%); Palembang 7
      males (4.75%), 1 female (0.11%); Surabaya 18 males (1.38%), 7 females (0.35%);
      Denpasar 12 males (2.97%), 1 female (0.24%), and Jakarta 55 males (4%), 28
      females (1.39%). The incidence of colorectal cancer is almost equal in every
      pathologic diagnostic centres. It is interesting that the incidence of rectal
      cancer was higher than colon cancer. In Jogjakarta the histopathological feature
      of stomach cancer was predominated by poorly differentiated adenocarcinoma, while
      colorectal cancer was predominated by well differentiated adenocarcinoma.
      CONCLUSIONS: The low incidence of gastric cancer in Indonesia in relation with H.
      Pylori and food consumption and the high ratio between rectal and colon cancer in
      correlation with the food consumption and it pathogenesis need further
      investigation.

PMID- 14728586
TI  - Higher consumption of green tea may enhance equol production.
AB  - BACKGROUND: Our previous case-control study revealed that Japanese living in
      Japan and Koreans living in Korea can be divided into equol producers who have an
      ability to metabolize daidzein to equol and non-producers, and that the incidence
      of prostate cancer is higher in the latter group. In the present study, we
      examined relationships between type of food intake and the capacity for equol
      production in Japanese subjects. METHODS: The subjects were the individuals
      analyzed for the ability to produce equol in our previous study and newly
      registered cases. From December 2000 to December 2002, 276 hospitalized patients
      were interviewed face-to-face and blood samples were collected before breakfast.
      These included 122 patients with prostate cancer and 154 age-matched controls.
      RESULTS: The frequency of equol producers (0.5 ng/ml or more) among cases and
      controls was 29% and 45%, respectively (p = 0.004). The consumption of soybeans
      and green tea were significantly higher in equol producers than in the non
      producers (p<0.05). By contrast, the consumption of selenium and fiber was
      significantly lower in equol producers (p<0.05). CONCLUSIONS: Our results suggest
      that higher consumption of soybean and green tea are strongly related to the
      establishment of a capacity for equol production.

PMID- 14728587
TI  - Histologic subtypes of hepatocellular carcinoma in the southern Thai population.
AB  - Since there has been no report on histologic subtypes of hepatocellular carcinoma
      (HCC) and its significance in the Thai population, the present study was
      conducted to elucidate the situation through appraisal of histologic and
      laboratory records. A total of 180 archived microscopic slides of HCC in
      Sonklanagarind Hospital from 1991 to 1998 were of good enough quality with
      sufficient tissue to be reviewed. The reclassified histologic subtypes were
      correlated with microscopic features and laboratory data. Of the 180 cases, 147
      were males and hepatitis B was the main etiologic factor. The histologic subtypes
      of HCC were trabecular 63.3%, compact 15.6%, scirrhous 7.8%, pseudoglandular 5%,
      and fibrolamellar 0.6%. There was no correlation between histologic subtypes and
      morphological findings, as well as HBV, HCV, and cirrhotic status. A correlation
      between AFP levels and the AST/ALT ratio was evident.

PMID- 14728588
TI  - Are cutaneous melanomas of specified thickness showing deeper levels of invasion
      at diagnosis?
AB  - Secular trends in Clark level were investigated by Breslow category for 8,432
      invasive cutaneous melanomas diagnosed in South Australia in 1980-2000. More
      recently diagnosed lesions were found to have deeper levels. After adjusting for
      age at diagnosis, tumour site, histology, and thickness measured in half
      millimetres, the relative odds (95% confidence limits) of penetration to the
      reticular dermis or subcutaneous fat were 1.99 (1.59, 2.50) for the 1987-93
      diagnostic period, and 2.82 (2.25, 3.54) for 1994-2000, when compared with 1980
      86. After adjusting for melanoma thickness, the secular trends for deeper lesions
      applied to a broad cross-section of socio-demographic sub-groups, tumour sites,
      and histological types. While this similarity in trend would be consistent with a
      measurement effect, a real change cannot be ruled out and increased emphasis on
      earlier detection may be warranted. The prognostic implications of changes in
      inter-relationships between measures of thickness and level require periodic re
      evaluation.

PMID- 14728589
TI  - Cervix cancer in Khon Kaen, northeast Thailand, 1985-1999.
AB  - The incidence of cancer of the cervix uteri in Khon Kaen Province is moderately
      high (age-standardised rate 16.8 per 100 000 person-years), with about a two-fold
      variation in incidence between different districts. Stage at presentation is
      considerably more advanced than in the United States and Europe, and there has
      been little change in incidence over the last 15 years. Currently, control of
      cervix cancer is through early detection and treatment. Screening programmes
      have, to date, been opportunistic, but a new national plan anticipates that all
      women will be screened six times during their lifetime. The results from Khon
      Kaen provide a benchmark against which the success of this policy can be
      evaluated.

PMID- 14728590
TI  - Dietary protocatechuic acid during the progression phase exerts chemopreventive
      effects on chemically induced rat tongue carcinogenesis.
AB  - The modifying effects of dietary administration of protocatechuic acid (PCA)
      during the progression phase of tongue carcinogenesis initiated with 4
      nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. For tumor
      progression we developed a new animal model, where rats initiated by 4-week
      treatment of 20 ppm 4-NQO in drinking water, received four cycles of 20 ppm 4-NQO
      to induce advanced tongue cancer (one cycle: 2 weeks of 4-NQO followed by 2 weeks
      of tap water), starting at 14 weeks after the initiation. In this model,
      metastasis of tongue cancer occurred in lungs. Starting two weeks before the
      cycle treatment with 4-NQO, animals were fed the 2000 ppm PCA containing diet and
      continued on this diet until the end of the study. At the termination of the
      experiment (week 32), the incidences of tongue neoplasms and preneoplastic
      lesions, polyamine levels in the tongue tissue, and cell proliferation activity
      estimated by morphometric analysis of silver-stained nucleolar organizer regions 
      protein were compared among the groups. Feeding with PCA containing diet during
      the progression phase significantly decreased the occurrence of advanced tongue
      squamous cell carcinoma with metastasis (P<0.05) and preneoplasia (hyperplasia
      and dysplasia) (P<0.001). In addition, PCA exposure decreased polyamine levels in
      the tongue tissue (P<0.001) during progression phase. Our results suggest that
      dietary PCA inhibits progression of 4-NQO-induced oral carcinogenesis, and such
      inhibition might be related to suppression of cell proliferation by PCA.

PMID- 14728591
TI  - Surveillance for endometrial cancer in postmenopausal breast cancer patients
      taking tamoxifen.
AB  - OBJECTIVES: To determine the prevalence of endometrial thickening and endometrial
      pathologies in postmenopausal breast cancer patients taking tamoxifen. MATERIALS
      AND METHODS: A total of 37 postmenopausal breast cancer patients receiving 20
      microg/day of tamoxifen treatment for at least 6 months at Srinagarind hospital
      were included in the study. Thorough history taking and physical examination as
      well as transvaginal ultrasonography were conducted for all patients. Fractional
      curettage was carried out in those whose endometrial thickness was found to be
      greater than 5 mm. RESULTS: Among 37 patients included in this study, the mean
      age was 56.35 years. The mean body weight and mean body mass index was 60.88 kg
      and 26.03 kg/m(2), respectively. The majority of patients (75.68%) had stage II
      disease. The mean + SD of endometrial thickness found in this study was 7.53 +
      5.16 mm. The prevalence of thickened endometrium (defined as ET > 5mm from TVS)
      was 59.46%. Among the 19 patients for whom fractional curettage was conducted,
      the majority (73.69%) exhibited inadequate endometrium for evaluation. Atrophic
      endometrium and other unremarkable changes were found in 21.05% of patients and
      it is important to note that endometrial adenocarcinoma was detected in 1 case
      (5.26%). CONCLUSIONS: The prevalence of thickened endometrium in postmenopausal
      breast cancer patients taking tamoxifen found in this study was extraordinarily
      high. These is, however, a discrepancy between the value and that for endometrial
      abnormalities detected histologically.

PMID- 14728592
TI  - No association of the mitochondrial genotype (Mt5178A/C) with six cancers in a
      Japanese population.
AB  - To examine an association between the mitochondrial DNA (mt5178) genotype and
      various cancers, we genotyped 1120 non-cancer controls and 930 cancer cases
      including esophageal, stomach, colorectal, lung, breast and malignant lymphoma in
      a sample of Japanese patients. The mt5178A/C was genotyped by the polymerase
      chain reaction with confronting two-pair primers (PCR-CTPP). The frequency of
      mt5178A/C within the non-cancer and cancer groups, and age distribution of
      subjects with mt5178A and C were investigated. Odd ratios (ORs) of the mt5178A
      and C genotypes were also examined. The frequency of mt5178A was 39.1% in non
      cancer subjects while frequencies in those having cancer included 39.0% in
      breast, 37.4% in colorectal, 45.1% in esophageal, 38.0% in lung, 41.5% in
      malignant lymphoma, and 38.8% in stomach cancer. There was no significant
      difference in the frequency of the mt5178 genotype among the six types of cancer
      studied. There was also no significant difference in the frequency of the mt5178
      genotype between non-cancer and cancer subjects regardless of total age with the
      exception that ages 40-49 years (the frequency of the mt5178A was higher in
      cancer subjects). There was a significant interaction term between age and the
      mt5178 genotype in older (age>=60) lung cancer patients. The cumulative frequency
      of mt5178C increased more markedly than that of mt5178A after age 40 in non
      cancer subjects, and after age 50 in cancer subjects ORs of the genotype were not
      significant for all cancers combined or for any individual site of cancer. In the
      present study, the mt5178 genotype seems to have no association with any of the
      cancers examined here. But an interaction term between the mt5178 genotype and
      aging on cancer was suggested with the Japanese population under study.

PMID- 14728593
TI  - Childhood cancer in Thailand: 1995-1997.
AB  - The incidences of childhood cancers in Thailand between 1995 and 1997 were
      determined from cancer registrations collected at five locations around the
      kingdom and compared with similar analyses performed at cancer registries in
      Asia, Europe and the USA. The incidence in Thailand was found to be lower than in
      some Asian and Western countries. Between 1988-1994 and 1995-1997, the incidence
      of childhood cancer rose 32.5%. As elsewhere in the world, leukemias, brain
      tumors and lymphomas comprised two-thirds of all childhood cancers. The age-peak
      for incidence was between 2 and 5 years, particularly for acute lymphoblastic
      leukemia. Carcinomas were rare. Several features of the cancer pattern correspond
      to other Asian populations, in particular the low incidence of Hodgkin s disease,
      Wilms  tumor and Ewing s sarcoma. Neuroblastoma was more common than in
      neighboring Southeast Asian countries.

PMID- 14728594
TI  - The experiences of smoking in school children up to and including high school
      ages and the current status of smoking habits; a survey of male high school
      students in Japan.
AB  - OBJECTIVES: The burden of tobacco-induced cancer is so heavy that every country
      should give the highest priority to tobacco control in its fight against cancer.
      The purpose of the present study was to investigate the actual conditions of
      tobacco smoking among boys in Japan. METHODS: A self-administered questionnaire
      survey. Two thousand and fourteen high school boys in Fukuoka City, Japan,
      answered unsigned self-administered anonymous questionnaires about tobacco
      smoking. RESULTS: Among 2014 students, 10.9% were current smokers. The rates of
      current smokers increased with the school age: 6.3% in the first grade; 11.3% in
      the second grade; and 15.5% in the third grade (P(trend)<0.01). A total of 35.1%
      of students had the experience of smoking and 30% experienced smoking before
      entering high school. Of the students with smoking experience, 28.6% answered
      that they started smoking because their friends had offered them cigarettes and
      52.5% of current smokers bought cigarettes from vending machines. CONCLUSIONS:
      Health education for anti-smoking in all primary and secondary schools as well as
      restriction of cigarette vending machines should be strongly recommended.

PMID- 14728595
TI  - Epidemiology of ocular malignancies in Karachi.
AB  - The study was conducted with the objective of examining descriptive
      epidemiological characteristics of malignant ocular tumours in Karachi (1998
      2002). The data for two hundred and forty two ocular malignancies registered at
      the Karachi Cancer Registry for Karachi Division during a 5-year period, from
      January 1(st) 1998 to December 31(st) 2002 were analysed. The age standardized
      incidence rate (ASIR) was 0.5/100,000 in males and 0.4/100,000 in females. The
      gender ratio (M:F) was 1.3. The mean age was 34.8 years (95% CI 30.1; 39.6) in
      males and 34.5 years (95% CI 28.0; 40.9) in females. A fourth of the malignancies
      were childhood tumours. The most common childhood malignancies were
      retinoblastomas and rhabdomyosarcomas, whereas the most common adult malignancies
      were conjunctival squamous cell carcinomas and melanomas. Approximately 97.0% of
      the tumours were histologically confirmed. The majority (62.5%) presented as low
      grade (grade 1) lesions, and were localized to the eye (50%) at the time of
      diagnosis. The annual incidence rates remained stable during this period. The
      crucial importance of ocular malignancies is the high 5-year survival rates,
      associated disability following unilateral or bilateral enucleation and the
      implications as preventable components of  Cancer Control Programs  This article
      provides demographic statistics, which could be useful for the foundation,
      establishment and monitoring of a component of an effective cancer control
      program, the risk factors of ocular malignancies being well established. It is
      recommended that public health education to prevent ultraviolet light related
      ocular malignancies, information on preventative sun protection behavior,
      legislation for occupation related ocular cancers and genetic counseling for
      familial retinoblastoma should be essential primary components of all National
      Cancer Control Programs even in apparently low risk countries. In the long-term
      perspective, these efforts should further reduce the incidence - meanwhile
      stabilization of incidence rates could be achieved. Early detection and
      standardized treatment will reduce the associated morbidity and mortality.

PMID- 14728596
TI  - Karyotypic evolution: cytogenetics follow-up study in childhood acute
      lymphoblastic leukemia.
AB  - Forty seven children affected with acute lymphoblastic leukemia (ALL) were
      cytogenetically investigated at diagnosis and all through different stages of the
      disease (remission and relapse). A clonal karyotypic abnormality was found in 32%
      at diagnosis (mainly comprised of cALLa+). A hyperdiploid mode with chromosome
      counts ranging from 47-58, was found to be most prominent among cALLa+ patients.
      The most common numerical aberrations were gain of chromosomes 2, 5, and 21. The
      structural aberrations at diagnosis were found to be del(9)(p22), inv(9)(p11q13)
      and del(19)(p12). None of the children showed ph+ chromosome. A good prognosis
      was found in cALLa+ children with an abnormal karyotype at diagnosis and of these
      children, those who showed karyotypic instability, had a significantly longer
      first remission time. The karyotypic evolution through remission(s) and
      relapse(s) revealed the occurrence of structural alterations, including changes
      in chromosomes 3, 6, 9, 21 and 22. However, irrespective of the karyotypic clonal
      nature at diagnosis, chromosome 9 was the most commonly involved chromosome
      through the course of disease.

PMID- 14728597
TI  - Probiotics and health.
AB  - Probiotics are described as live microbial food ingredients that are beneficial
      to health of the of host, especially by improving intestinal microbial balance.
      The major consumption of probiotics is in dairy-based foods form, which is
      containing intestinal species of Lactobacillus and Bifidobacterium. A number of
      potential benefits of probiotics have been proposed, including: adherence to
      cells; exclusion or reduction of pathogenic adherence; production of acids,
      hydrogen peroxide, and bacteriocins antagonistic to pathogen growth; safe,
      noninvasive, noncarcinogenic and nonpathogenic characteristics; and congregation
      to form a normal balanced flora. The interrelation between probiotics and health
      are reviewed in this article.

PMID- 14728598
TI  - Ethical issues for cancer screening.
AB  - In recent years medical ethics has become an undisputed part of medical studies.
      Many people believe that modern advances in medical technology - such as the
      development of dialysis machines, respirators, magnetic resonance imaging and
      genetic testing and types of cancer screenings - have created bioethical dilemmas
      that confront physicians in the 21st century. Debates over research and screening
      ethics have until recently revolved around two related questions: the voluntary,
      informed consent of subjects, and the appropriate relationship between risk and
      benefit to subjects. Every patient has a right to full and accurate information
      about his or her medical condition. This legal principle arose primarily through
      court decisions concerning informed consent, but over time physicians recognized
      that most patients prefer to learn the truth about their condition and use the
      information well. To screen is to search for disease in the absence of symptoms
      or, in other words, to attempt to find disease in someone not thought to have a
      disease. Examples of screening include routine mammography to detect breast
      cancer, routine pap smears to detect cervical cancer, and routine Prostate
      Specific Antigen (PSA) testing to detect prostate cancer. Ethical principles to
      be followed in cancer screening programmes are intended mainly to minimize
      unnecessary harm for the participating individuals. Numerous ethical questions
      can be raised about the practice of screening for disease. Here, we examine four
      leading cancer killers worldwide and we review the screening of protocols of
      these cancer types and their possible ethics.

PMID- 14728599
TI  - Vesicle budding from endoplasmic reticulum is involved in calsequestrin routing
      to sarcoplasmic reticulum of skeletal muscles.
AB  - CS (calsequestrin) is an acidic glycoprotein of the SR (sarcoplasmic reticulum)
      lumen and plays a crucial role in the storage of Ca2+ and in excitation
      contraction coupling of skeletal muscles. CS is synthesized in the ER
      (endoplasmic reticulum) and is targeted to the TC (terminal cisternae) of SR via
      mechanisms still largely unknown, but probably involving vesicle transport
      through the Golgi complex. In the present study, two mutant forms of Sar1 and
      ARF1 (ADP-ribosylation factor 1) were used to disrupt cargo exit from ER-exit
      sites and intra-Golgi trafficking in skeletal-muscle fibres respectively. Co
      expression of Sar1-H79G (His79-->Gly) and recombinant, epitope-tagged CS, CSHA1
      (where HA1 stands for nine-amino-acid epitope of the viral haemagglutinin 1),
      barred segregation of CSHA1 to TC. On the other hand, expression of ARF1-N126I
      altered the subcellular localization of GM130, a cis -medial Golgi protein in
      skeletal-muscle fibres and myotubes, without interfering with CSHA1 targeting to
      either TC or developing SR. Thus active budding from ER-exit sites appears to be
      involved in CS targeting and routing, but these processes are insensitive to
      modification of intracellular vesicle trafficking and Golgi complex disruption
      caused by the mutant ARF1-N126I. It also appears that CS routing from ER to SR
      does not involve classical secretory pathways through ER-Golgi intermediate
      compartments, cis -medial Golgi and trans -Golgi network.

PMID- 14728601
TI  - Editorial: the challenge of dengue vaccine development and introduction.

PMID- 14728600
TI  - Defining the function of xeroderma pigmentosum group F protein in psoralen
      interstrand cross-link-mediated DNA repair and mutagenesis.
AB  - Many commonly used drugs, such as psoralen and cisplatin, can generate a very
      unique type of DNA damage, namely ICL (interstrand cross-link). An ICL can
      severely block DNA replication and transcription and cause programmed cell death.
      The molecular mechanism of repairing the ICL damage has not been well
      established. We have studied the role of XPF (xeroderma pigmentosum group F)
      protein in psoralen-induced ICL-mediated DNA repair and mutagenesis. The results
      obtained from our mutagenesis studies revealed a very similar mutation frequency
      in both human normal fibroblast cells and XPF cells. The mutation spectra
      generated in both cells, however, were very different: most of the mutations
      generated in the normal fibroblast cells were T167-->A transversions, whereas
      most of the mutations generated in the XPF cells were T167-->G transversions.
      When a wild-type XPF gene cDNA was stably transfected into the XPF cells, the
      T167-->A mutations were increased and the T167-->G mutations were decreased. We
      also determined the DNA repair capability of the XPF cells using both the host
      cell reactivation and the in vitro DNA repair assays. The results obtained from
      the host-cell reactivation experiments revealed an effective reactivation of a
      luciferase reporter gene from the psoralen-damaged plasmid in the XPF cells. The
      results obtained from the in vitro DNA repair experiments demonstrated that the
      XPF nuclear extract is normal in introducing dual incisions during the nucleotide
      excision repair process. These results suggest that the XPF protein has important
      roles in the psoralen ICL-mediated DNA repair and mutagenesis.

PMID- 14728602
TI  - Does increased general schooling protect against HIV infection? A study in four
      African cities.
AB  - BACKGROUND: The association between educational attainment and risk of HIV
      infection varies between populations and over time. Earlier studies in sub
      Saharan Africa have found that those with more education are at increased risk of
      HIV infection. METHODS: We investigated the associations between general
      schooling and both HIV and herpes simplex-2 (HSV-2) infection using data from the
      multicentre study on factors determining the differential spread of HIV in four
      African cities. Cross-sectional general population studies were conducted in 1997
      1998 in Cotonou (Benin), Yaounde (Cameroon), Kisumu (Kenya), and Ndola (Zambia),
      including about 2000 adults in each city. RESULTS: There was no association
      between schooling and HIV infection in men or women in Kisumu or Ndola. Women in
      Yaounde and men in Cotonou, with more schooling, were less likely to be HIV
      positive. These associations persisted after adjusting for sociodemographic
      factors. Similar trends in men in Yaounde and women in Cotonou were not
      statistically significant. Increased schooling was associated with significantly
      decreased risk of HSV-2 infection in women in Kisumu and Ndola and men in
      Cotonou. In all the cities those with more education tended to report less risky
      sexual behaviour. CONCLUSIONS: There was no evidence of an increased risk of HIV
      infection associated with education as seen in earlier studies. In each city
      there was some evidence of lower HIV or HSV-2 infection rates and less risky
      sexual behaviour associated with increased education levels. The most educated
      may be responding more readily to health education programmes. The challenge is
      to extend this to the rest of the population.

PMID- 14728604
TI  - Review: multidrug-resistant tuberculosis: public health challenges.

PMID- 14728603
TI  - Pregnancy interval and delivery outcome among HIV-seropositive and HIV
      seronegative women in Kisumu, Kenya.
AB  - OBJECTIVE: A short pregnancy interval (PI) has been associated with increased
      child mortality, but mechanisms are unclear. We studied factors associated with
      PI and the effect of PI on birthweight and haemoglobin. METHODS: Information was
      analysed from 2218 multigravidae who were recruited at the prenatal clinic (1758)
      or in the labour ward (460) of the Provincial Hospital in Kisumu between June
      1996 and July 2000 for a study to assess the interaction between placental
      malaria and vertical HIV transmission. RESULTS: The HIV prevalence was 28.9%. HIV
      seropositivity, older age, being unmarried, and <8 years of education were
      associated with a prolonged PI; among all women, a stillbirth, abortion, or death
      of a liveborn child as outcome of the previous pregnancy, and death of a child
      other than the last born among HIV-seronegative women, were associated with a
      shortened PI. No significant effect of short PI (an interval <24 months) on low
      birth weight (LBW), prematurity, small-for-gestational-age infants or maternal
      anaemia was evident. An abortion, stillbirth, or death of a liveborn child as
      outcome of the previous pregnancy was associated at the present delivery with LBW
      among HIV-seronegative women [adjusted odds ratio (AOR) 3.33, 95% confidence
      interval (CI) 1.63-6.81], and a low haemoglobin (<11 g/dl) among HIV-seropositive
      women (AOR 2.01, 95% CI 1.05-4.03 in the third trimester). CONCLUSION: Public
      health efforts to ensure 'adequate' birth spacing may run contrary to family
      planning decisions to replace a deceased child and may be spent on prenatal
      issues like prevention of anaemia, and vertical HIV transmission.

PMID- 14728605
TI  - Epidemiological and entomological surveillance of the co-circulation of DEN-1,
      DEN-2 and DEN-4 viruses in French Guiana.
AB  - We surveyed the disease epidemiology of dengue in French Guiana after the first
      dengue haemorrhagic fever epidemic from 1991 to 1993 and during an endemic period
      from 1993 to 1995. DEN-1, DEN-2 and DEN-4 viruses were isolated from patients and
      DEN-4 was also isolated from Aedes aegypti mosquitoes. Cases of dengue were
      reported from all over the country, not only from urban areas, but also from
      rural areas and isolated human settlements, indicating widespread circulation of
      the viruses. The mosquito vector A. aegypti was found in all inhabited areas of
      French Guiana and small outdoor containers were the most common breeding grounds.
      Some ecological features of A. aegypti, such as larvae breeding in Bromeliad
      plants in the rainforest, a non-exclusive anthropophily and a high vertical
      transmission rate for dengue viruses, indicate that A. aegypti can behave as a
      reservoir for dengue viruses in silent areas. Dengue viruses may survive at an
      endemic level and cause outbreaks when unknown conditions become more favourable.
      This finding adds to our knowledge of the natural history of dengue viruses in
      the Americas.

PMID- 14728606
TI  - The efficacy of chloroquine, sulfadoxine-pyrimethamine and a combination of both
      for the treatment of uncomplicated Plasmodium falciparum malaria in an area of
      low transmission in western Uganda.
AB  - We conducted an efficacy study of chloroquine (CQ), sulfadoxine-pyrimethamine
      (SP) and a combination of both (SP+CQ) for the treatment of uncomplicated malaria
      in an area of low transmission with low drug pressure. On day 3, fever clearance
      was 97.4% (95% CI, 86.8-99.9), 100% (95% CI, 87.2-100) and 96.6% (95% CI, 82.2
      99.9) in the CQ, SP and SP+CQ groups, respectively, (P=0.65). On day 14, clinical
      success was 92.5% (95% CI, 79.6-98.4), 100% (95% CI, 87.2-100) and 100% (95% CI,
      88.1-100) in the CQ, SP and CQ+SP groups, respectively. Clinical failure was seen
      in 7.5% with 5% (95% CI, 0.61-16.9) early treatment failure and 2.5% (95% CI,
      0.06-13.2) late treatment failure of cases in the CQ group and 0% in the SP and
      SP+CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI,
      2.8-23.7), 18.5% (95% CI, 6.3-38.1) and 6.9% (95% CI, 0.85-22.8) for the CQ, SP
      and SP+CQ, respectively (P=0.37). There was no age-dependent difference in
      clinical failure or parasitological resistance in any of the treatment groups and
      prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The
      findings of this study suggest that CQ is still effective for the treatment of
      uncomplicated malaria in this area of low transmission and SP. However,
      combination therapy of SP+CQ is recommended to delay the development SP
      resistance, and regular surveillance for emerging CQ and SP resistance is needed
      to plan for alternative antimalarial drug regimens.

PMID- 14728607
TI  - Addition of artesunate to chloroquine for treatment of Plasmodium falciparum
      malaria in Gambian children causes a significant but short-lived reduction in
      infectiousness for mosquitoes.
AB  - OBJECTIVES: Combination therapy using existing anti-malarials together with
      artesunate (AS) has been advocated as a method to slow the spread of drug
      resistance. We assessed the effect on Plasmodium falciparum transmissibility of
      the addition of AS to chloroquine (CQ) in an area of The Gambia where resistance
      to CQ is increasing. METHODS: Gambian children with acute uncomplicated P.
      falciparum malaria were treated with either CQ monotherapy (n=120) or the
      combination of CQ plus three doses of AS (CQ/AS; n=352). Post-treatment sexual
      stage parasitaemia was assessed during a 4-week follow-up period. Experimental
      infections of Anopheles gambiae s.s. mosquitoes were performed with blood from
      patients who were carrying gametocytes 7 days after starting treatment (n=69).
      RESULTS: The addition of AS significantly reduced post-treatment prevalence and
      mean density of gametocytes in the first 14 days (day 7: 43.7% vs. 12.4%,
      62.4/microl vs. 6.2/microl; day 14: 32.9% vs. 3.7%; 21.9/microl vs. 5.2/microl;
      CQ vs. CQ/AS), although by day 28 the benefits of the combination were
      substantially less marked (40.5% vs. 21.8%; 23.0/microl vs. 63.1/microl; CQ vs.
      CQ/AS). The duration of gametocyte carriage over the study period was
      significantly lower in the CQ/AS group (5.2 days vs. 1.5 days; CQ vs. CQ/AS). The
      estimated infectious proportion of children at day 7 was also lower in the
      combination group (19.2% vs. 3.4%; CQ vs. CQ/AS), as were the proportion of
      mosquitoes infected and mean oocyst density (11.5% vs. 0.9%; 0.3 vs. 0.01; CQ vs.
      CQ/AS). Treatment failure was associated with threefold and twofold higher
      gametocyte carriage rates during follow-up in CQ and CQ/AS groups, respectively
      (P<0.001 in both cases), and 26-fold and 2.3-fold higher intensity of infection
      at day 7 among CQ- and CQ/AS-treated children, respectively (P=0.002 and 0.30,
      respectively). CONCLUSION: The benefits of adding AS to CQ monotherapy in
      lowering gametocyte prevalence and density were transient, suggesting that the
      addition of AS delayed, but did not prevent, the emergence of gametocytes. This
      is consistent with our finding that treatment failure, and thus the presence of
      CQ-resistant parasites, was significantly associated with a higher gametocyte
      carriage rate in both treatment groups. At day 7, CQ monotherapy significantly
      favoured transmission of resistant infections, which showed an 11-fold greater
      intensity of transmission compared with infections that were successfully
      treated. In contrast, the combination of CQ/AS did not significantly favour
      resistant infections at day 7. We conclude that significant transmission
      reduction is achieved by the combination but is not maintained because of the
      recrudescence of CQ-resistant parasites.

PMID- 14728608
TI  - Adherence to the combination of sulphadoxine-pyrimethamine and artesunate in the
      Maheba refugee settlement, Zambia.
AB  - Artemisinin-based combination therapy (ACT) is one strategy recommended to
      increase cure rates in malaria and to contain resistance to Plasmodium
      falciparum. In the Maheba refugee settlement, children aged 5 years or younger
      with a confirmed diagnosis of uncomplicated falciparum malaria are treated with
      the combination of sulphadoxine-pyrimethamine (1 day) and artesunate (3 days). To
      measure treatment adherence, home visits were carried out the day after the last
      treatment dose. Patients who had any treatment dose left were considered
      certainly non-adherent. Other patients' classification was based on the answers
      to the questionnaire: patients whose caretakers stated the child had received the
      treatment regimen exactly as prescribed were considered probably adherent; all
      other patients were considered probably non-adherent. Reasons for non-adherence
      were assessed. We found 21.2% (95% CI [15.0-28.4]) of the patients to be
      certainly non-adherent, 39.4% (95% CI [31.6-47.6]) probably non-adherent, and
      39.4% (95% CI [31.6-47.6]) probably adherent. Insufficient explanation by the
      dispenser was identified as an important reason for non-adherence. When
      considering the use of ACT, the issue of patient adherence remains challenging.
      However, it should not be used as an argument against the introduction of ACT.
      For these treatment regimens to remain efficacious on a long-term basis, specific
      and locally adapted strategies need to be implemented to ensure completion of the
      treatment.

PMID- 14728609
TI  - The changing epidemiology of malaria in Ifakara Town, southern Tanzania.
AB  - Between 1995 and 2000 there were marked changes in the epidemiology of malaria in
      Ifakara, southern Tanzania. We documented these changes using parasitological and
      clinical data from a series of community- and hospital-based studies involving
      children up to the age of 5 years. There was a right shift and lowering in the
      age-specific parasite prevalence in the community-based cohort studies. The
      incidence of clinical malaria in placebo-receiving infants in additional study
      cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an
      incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At
      the same time, there was an increase in the total number of malaria admissions
      and a marked right shift in the age pattern of these admissions (median age in
      1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria
      deaths remained in infants. We discuss how these dramatic changes in the
      epidemiology of malaria may have arisen from the use of currently available
      malaria control tools. Caution is required in the interpretation of hospital
      based data as it is likely to underestimate the impact of anaemia on mortality in
      the community, where most paediatric deaths occur. Even in low/moderate malaria
      transmission settings, where older children suffer most malaria episodes,
      targeting effective malaria control at infants may produce important reductions
      in infant mortality caused by malaria.

PMID- 14728610
TI  - Use of antenatal care services and intermittent preventive treatment for malaria
      among pregnant women in Blantyre District, Malawi.
AB  - Malaria in pregnancy contributes to low birth weight and increased infant
      mortality. As part of WHO's Roll Back Malaria initiative, African heads of state
      pledged that by 2005, 60% of pregnant women will receive malaria chemoprophylaxis
      or intermittent preventive treatment (IPT). We performed a cluster sample survey
      to study the use of sulfadoxine-pyrimethamine (SP) for IPT among recently
      pregnant women in February 2000 in Blantyre District, Malawi. Among 391 women in
      the sample, 98.6% had attended antenatal clinic at least once and 90.2% knew that
      SP/IPT was recommended during pregnancy. Overall, only 36.8% received the full
      recommended two-dose regimen of SP/IPT. Using data from 187 women with antenatal
      clinic cards, we found that residence location, housing type and
      gender/age/education of the head of household were not associated with failure to
      receive SP/IPT. Adjusting for education, multigravid women were more likely not
      to receive the recommended SP/IPT regimen (RR 1.2, 95% CI 1.02-1.5, P=0.03). A
      substantial effort to improve the delivery and use of SP/IPT in Malawi will be
      necessary, but the Roll Back Malaria 2005 goal appears achievable.

PMID- 14728611
TI  - Megazol combined with suramin improves a new diagnosis index of the early meningo
      encephalitic phase of experimental African trypanosomiasis.
AB  - In human African trypanosomiasis (HAT), the parasites invade the central nervous
      system (CNS), leading to the development of meningo-encephalitis and an
      irreversible demyelinating process, which kills the patient unless specific
      treatment is undertaken. Among the experimental trypanocides, the nitroimidazole
      derivative megazol alone at optimal doses does not cure late-stage disease tested
      in mouse models, however the combination of suramin and megazol is able to cure
      infected mice without CNS involvement. We recently developed an experimental
      model of HAT with a sharp decrease in both the food intake and the body weight
      which may constitute an effective index of the early meningo-encephalitic phase.
      Using this model, we tested this hypothesis by the exclusive effectiveness of a
      megazol and suramin combination treatment to eliminate CNS trypanosomes. Sprague
      Dawley rats were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake
      and body weight were measured daily from the day of infection to death.
      Haematocrit was measured twice a week. Treatment consisted of 20 mg suramin per
      kg body weight administered intraperitoneally (i.p.) alone, or three daily doses
      (80 mg/kg) of megazol given per os, or suramin (20 mg/kg, i.p.) followed 24 h
      later by three daily doses (80 mg/kg) of megazol given per os. Treatment was
      followed by an increase in daily body weight and food intake similar to those of
      the control animals, 2 weeks after treatment. The anaemia developed after
      infection is also cleared as shown by the haematocrit measurements. The rats
      treated with megazol alone died about 29 days after treatment and those treated
      with suramin, after about 26 days. Seven months later, no signs of relapse were
      seen in 10 of 12 rats treated with the therapeutic combination, indicating that
      this chemotherapy regimen was curative. The results support our previous finding,
      i.e. the decrease in body weight may constitute a diagnosis index of the early
      meningo-encephalitic phase.

PMID- 14728612
TI  - Epilepsy prevalence in rural Zambia: a door-to-door survey.
AB  - OBJECTIVES: To identify people with epilepsy (PWE) in our Zambian catchment area
      of 55,000 people. METHODS: A nine-item, previously validated screening instrument
      for detecting epilepsy in developing countries was forward-and-back translated
      into Chitonga. Early piloting indicated poor specificity among children, so three
      questions were added. Local census data were used to estimate the population at
      risk. Community health workers conducted screening interviews with household
      heads. All positive screens were referred for physician assessment. A blinded
      neurologist assessed a randomly selected subset (100 positives, 50 negatives) to
      determine screening instrument characteristics. RESULTS: We identified 799 people
      with possible epilepsy (unadjusted prevalence 14.5/1000). The adapted instrument
      exhibited 86% specificity (adjusted prevalence 12.5/1000). False positives
      occurred primarily among children who had experienced multiple malaria-associated
      seizures. Age-specific rates were highest for children aged 5-15 years
      (26.2/1000) and for people over 65 years (15.9/1000). Males were
      disproportionately represented (55.8%vs. 44.2%, P<0.05), although this trend
      reversed after childbearing age. CONCLUSION: Even using a relatively conservative
      definition, we identified almost 700 PWE. Use of the recommended epidemiological
      definitions would likely have yielded higher prevalence rates. The age-specific
      prevalence did not follow patterns described where neurocysticercosis is the
      commonest cause of epilepsy. Trends in age- and gender-specific prevalence may
      offer a clue to the aetiology of epilepsy in this region.

PMID- 14728613
TI  - Soluble transferrin receptor in Aboriginal children with a high prevalence of
      iron deficiency and infection.
AB  - OBJECTIVES: Aboriginal children in tropical Australia have a high prevalence of
      both iron deficiency and acute infections, making it difficult to differentiate
      their relative contributions to anaemia. The aims of this study were to compare
      soluble transferrin receptor with ferritin in iron deficiency anaemia (IDA), and
      to examine how best to distinguish the effect of iron deficiency from infection
      on anaemia. METHODS: We conducted a prospective study of 228 admissions to Royal
      Darwin Hospital in children from 6 to 60 months of age. Transferrin receptor
      concentrations were measured by a particle-enhanced immunoturbidimetric assay and
      ferritin by a microparticle enzyme immunoassay. RESULTS: On multiple regression,
      the best explanatory variables for haemoglobin differences (r2=33.7%, P<0.001)
      were mean corpuscular volume (MCV), red cell distribution width (RDW) and C
      reactive protein (CRP); whereas transferrin receptor and ferritin were not
      significant (P>0.4). Using > or =2 abnormal indices (MCV, RDW, blood
      film)+haemoglobin <110 g/l as the reference standard for IDA, transferrin
      receptor produced a higher area under the curve on receiver operating
      characteristic curve analysis than ferritin (0.79 vs. 0.64, P<0.001) or the
      transferrin receptor-ferritin index (0.77). On logistic regression, the effect of
      acute infection (CRP) on haemoglobin was significant (P<0.001) at cut-offs of 105
      and 110 g/l, but not at 100 g/l when only iron deficiency indicators (MCV, RDW,
      blood film) were significant. CONCLUSIONS: Transferrin receptor does not
      significantly improve the diagnosis of anaemia (iron deficiency vs. infection)
      over full blood count and CRP, but in settings with a high burden of infectious
      diseases and iron deficiency, it is a more reliable adjunctive measure of iron
      status than ferritin.

PMID- 14728614
TI  - Household drinking water in developing countries: a systematic review of
      microbiological contamination between source and point-of-use.
AB  - OBJECTIVE: To assess the extent and causes of microbiological contamination of
      household drinking water between source and point-of-use in developing countries.
      METHODS: A systematic meta-analysis of 57 studies measuring bacteria counts for
      source water and stored water in the home to assess how contamination varied
      between settings. RESULTS: The bacteriological quality of drinking water
      significantly declines after collection in many settings. The extent of
      contamination after water collection varies considerably between settings, but is
      proportionately greater where faecal and total coliform counts in source water
      are low. CONCLUSIONS: Policies that aim to improve water quality through source
      improvements may be compromised by post-collection contamination. Safer household
      water storage and treatment is recommended to prevent this, together with point
      of-use water quality monitoring.

PMID- 14728615
TI  - The use of non-prescribed medication in the first 3 months of life in rural South
      Africa.
AB  - OBJECTIVE: This paper describes the use of non-prescribed medications given to a
      cohort of infants in the first 3 months of life in a rural South African
      district, and discusses some of the implications for primary health care.
      METHODS: As part of an ongoing study on breastfeeding, a cohort of 110 infants
      were visited at home at 6 and 12 weeks of age. Any medications given to the
      infant since the last visit, the reasons for their administration, and any visits
      made to traditional healers were recorded via a semi-structured questionnaire.
      Determinants of administration of non-prescribed medication were analysed,
      including maternal age, education, infant gender and socio-economic factors.
      RESULTS: A total of 107 (97%) infants received non-prescribed medications in the
      first 3 months of life: 98 (89%) rectally and 64 (58%) orally. The most common
      enema contained traditional Zulu medicine made from herbs, given more than once
      weekly, usually for perceived constipation; the most common oral medication was
      gripe water, given once daily, mainly for 'colic' or 'wind'. Twenty-nine (26%)
      mothers had consulted a traditional healer, most commonly because of concerns
      about a capillary naevus, thought to cause pain. Mothers with a 'clean' water
      supply were more likely to give non-prescribed oral medications than those
      without (OR=2.7 and P=0.0223), whilst those who had no education were less likely
      to administer them than those who had completed school (OR=0.19 and P=0.0326).
      CONCLUSIONS: Non-prescribed medications are given almost universally to young
      infants in our area, irrespective of socio-economic class. Health professionals
      need to be aware of the extent of, and reasons for, administration of non
      prescribed medications to young infants, so that effective health messages can be
      targeted at mothers and caregivers.

PMID- 14728616
TI  - The cost and cost-effectiveness of malaria vector control by residual insecticide
      house-spraying in southern Mozambique: a rural and urban analysis.
AB  - OBJECTIVES: To compare two separately funded, but operationally similar, residual
      household-spraying (RHS) initiatives; one rural and one peri-urban in southern
      Mozambique. METHODS: The rural programme is a regional project involving the
      participation and co-ordination of organizations across three countries in
      southern Africa and is focussed on control in an area in Mozambique of 7552 km2.
      The second programme focuses on spraying a peri-urban community within a 10-km
      radius around MOZAL, an aluminium smelter plant of area 410 km2. An ingredients
      approach was used to derive unit costs for both the rural and peri-urban spraying
      programmes using detail retrospective cost data and effectiveness indicators.
      RESULTS: The economic cost per person covered per year using Carbamates for
      indoor residual spraying (IRS) in the rural area, excluding the costs of project
      management and monitoring and surveillance was $3.48 and in the peri-urban area,
      $2.16. The financial costs per person covered in the rural area and peri-urban
      area per year were $3.86 and $2.41, respectively. The economic costs per person
      covered were respectively increased by 39% and 31% when project management and
      monitoring and surveillance were included. The main driving forces behind the
      costs of delivering RHS are twofold: the population covered and insecticide used.
      Computed economic and financial costs are presented for all four insecticide
      families available for use in RHS. CONCLUSIONS: The results from both these
      initiatives, especially the rural area, should be interpreted as conservative
      cost estimates as they exclude the additional health gains that the newly
      introduced programmes have had on malaria rates in the neighbouring areas of
      South Africa and Swaziland. Both these initiatives show that introducing an IRS
      programme can deliver a reduction in malaria-related suffering providing
      financial support, political will, collaborative management and training and
      community involvement are in place.

PMID- 14728617
TI  - In situ measured elimination of Vibrio cholerae from brackish water.
AB  - In situ elimination of fluorescently labelled Vibrio cholerae (FLB) was measured
      in two saline water bodies in Mexico: in a brackish water lagoon, Mecoacan (Gulf
      of Mexico; State of Tabasco) and an athalassohaline lake, Alchichica (State of
      Puebla). Disappearance rates of fluorescently labelled V. cholera O1 showed that
      they were eliminated from the environment at an average rate of 32% and 63%/day,
      respectively (based on the bacterial standing stocks). The indirect
      immunofluorescence method confirmed the presence of V. cholerae O1 in the lagoon.
      However, the elimination of FLB was not directly related either to the presence
      or absence of the bacterium in the water body or to the phytoplankton
      concentration.

PMID- 14728618
TI  - Retaking sleeping sickness control in Angola.
AB  - Africa is severely affected by a resurgence of human African trypanosomiasis
      (HAT) at epidemic proportions. We report the results of the first 5 years of a
      HAT control programme in northern Angola run by the non-governmental organization
      (NGO) ANGOTRIP. In the period between 1996 and 2001, 13 426 patients were
      screened for HAT. The mortality rate of patients in stage II who were treated
      with melarsoprol fell from 7.5% to 2.9%, possibly as a result of training and the
      standardization of treatment protocols. A total of 191,578 people in three
      provinces of Angola were screened for HAT. Vector control activities were
      initiated using Lancien traps. Our experiences reflect the connection between war
      and the increasing incidence of disease, but also demonstrate that HAT control is
      possible by dedicated NGOs in close cooperation with national institutions even
      under extremely difficult circumstances.

PMID- 14728619
TI  - Measuring schistosomiasis case management of the health services in Ghana and
      Mali.
AB  - The World Health Organization recommends passive case detection by regular health
      services as a minimum strategy for schistosomiasis morbidity control. To evaluate
      preparedness of the health systems in Ghana and Mali, we presented four clinical
      scenarios, two with blood in urine (main early symptom of Schistosoma
      haematobium) and two with (bloody) diarrhoea (main early symptom of S. mansoni),
      to health workers. We requested the health personnel for an initial diagnosis and
      case management strategy without providing information about our primary interest
      in schistosomiasis. The information was used to determine the chance that a
      person reporting with symptoms that might have been caused by schistosomiasis
      would receive praziquantel. All selected health workers participated. Their
      initial diagnosis was frequently S. haematobium for both scenarios with blood in
      urine. For the two scenarios with (bloody) diarrhoea, only few mentioned S.
      mansoni. At health centre level, case management in Mali mainly consisted of
      direct prescription of medication, whereas in Ghana health workers often referred
      to a hospital or requested a diagnostic test. The ultimate probability of
      prescribing praziquantel was relatively high for the scenarios with blood in
      urine, 60% in Ghana and 75% in Mali, but very low for both scenarios with
      (bloody) diarrhoea (<20%). Of those health care facilities that would prescribe
      praziquantel, 60% (Ghana) and 80% (Mali) had it in stock. In conclusion, the
      clinical scenario study showed that patients reporting with blood in urine will
      be treated with praziquantel at approximately half of the health care facilities,
      whereas of those presenting with (bloody) diarrhoea only few would receive
      treatment with praziquantel. Considering these facts, it is questionable if
      passive case detection is a sufficient basis for effective schistosomiasis
      morbidity control, especially for S. mansoni infection.

PMID- 14728620
TI  - Test strip detection of Wuchereria bancrofti amplified DNA in wild-caught Culex
      pipiens and estimation of infection rate by a PoolScreen algorithm.
AB  - Bancroftian filariasis is targeted for elimination in the Nile Delta of Egypt.
      Improved simple methods are needed for monitoring Wuchereria bancrofti infection
      in the mosquito vector and thereby the success of elimination programmes. We
      evaluated the performance of the SspI-PCR assay combined with a DNA Detection
      Test StripTM method and used the PoolScreen algorithm method for estimating
      mosquito infection rates. A total of 769 indoor-resting Culex pipiens were
      captured in 79 randomly selected houses from a filaria-endemic village in the
      Nile Delta of Egypt (24.4% antigenaemia and 8.6% microfilaraemia). Collected
      mosquitoes were pooled by house, and assayed by the SspI-PCR. Amplified parasite
      DNA was detected by both electrophoresis of agarose gel stained with ethidium
      bromide (EtBr) and by test strips. PCR based on EtBr and test strip methods
      identified 43 (54.4%) and 45 (56.9%) houses, respectively, as being filaria
      positive. The minimum mosquito infection rate, assuming one infected female/pool
      was 6.85% by the PCR test strips. Mosquito infection rate calculated by the
      PoolScreen2 algorithm software amounted to 8.1% [95% confidence interval 5.85,
      10.47]. Because it is faster and safer, the PCR test strip is a practical tool,
      especially when combined with the PoolScreen algorithm method, for xenomonitoring
      the success of elimination programmes.

PMID- 14728621
TI  - Malaria transmission dynamics at a site in northern Ghana proposed for testing
      malaria vaccines.
AB  - We studied the malaria transmission dynamics in Kassena Nankana district (KND), a
      site in northern Ghana proposed for testing malaria vaccines. Intensive mosquito
      sampling for 1 year using human landing catches in three micro-ecological sites
      (irrigated, lowland and rocky highland) yielded 18 228 mosquitoes. Anopheles
      gambiae s.l. and Anopheles funestus constituted 94.3% of the total collection
      with 76.8% captured from the irrigated communities. Other species collected but
      in relatively few numbers were Anopheles pharoensis (5.4%) and Anopheles rufipes
      (0.3%). Molecular analysis of 728 An. gambiae.s.l. identified Anopheles gambiae
      s.s. as the most dominant sibling species (97.7%) of the An. gambiae complex from
      the three ecological sites. Biting rates of the vectors (36.7 bites per man per
      night) were significantly higher (P<0.05) in the irrigated area than in the non
      irrigated lowland (5.2) and rocky highlands (5.9). Plasmodium falciparum
      sporozoite rates of 7.2% (295/4075) and 7.1% (269/3773) were estimated for An.
      gambiae s.s. and An. funestus, respectively. Transmission was highly seasonal,
      and the heaviest transmission occurred from June to October. The intensity of
      transmission was higher for people in the irrigated communities than the non
      irrigated ones. An overall annual entomological inoculation rate (EIR) of 418
      infective bites was estimated in KND. There were micro-ecological variations in
      the EIRs, with values of 228 infective bites in the rocky highlands, 360 in the
      lowlands and 630 in the irrigated area. Approximately 60% of malaria transmission
      in KND occurred indoors during the second half of the night, peaking at daybreak
      between 04.00 and 06.00 hours. Vaccine trials could be conducted in this
      district, with timing dependent on the seasonal patterns and intensity of
      transmission taking into consideration the micro-geographical differences and
      vaccine trial objectives.

PMID- 14728622
TI  - Genetic markers of resistance to pyrimethamine and sulfonamides in Plasmodium
      falciparum parasites compared with the resistance patterns in isolates of
      Escherichia coli from the same children in Guinea-Bissau.
AB  - The antifolate drugs sulphadoxine and pyrimethamine are used for treatment of
      chloroquine-resistant Plasmodium falciparum in Africa. Resistance to
      pyrimethamine has been associated with point mutations in the dhfr-gene and
      resistance to sulphadoxine with mutations in the dhps-gene. There is concern that
      the use of the antifolates trimethoprim and sulphamethoxazole for treatment of
      other infectious diseases will result in the selection of malaria parasites with
      mutations in these genes. In Guinea-Bissau, where sulfonamide and trimethoprim
      containing drugs have been used extensively, we decided to assess the prevalence
      of mutations in the dhfr-and dhps-gene in P. falciparum isolated from children
      suffering from acute malaria and to assess the resistance patterns to
      trimethoprim/sulphamethoxazole in Escherichia coli isolated from the same
      patients. A thick film and a blood sample for polymerase chain reaction (PCR)
      were obtained from 100 children attending the Bandim Health Centre in Bissau with
      symptoms compatible with malaria. Furthermore, a stool sample was collected from
      the same children and cultured for E. coli. Of the cultured E. coli, 67% were
      resistant both to sulfonamides and trimethoprim, 4% to sulfonamides alone, 3% to
      trimethoprim alone while 26% were fully sensitive to both drugs. PCR was
      successfully performed in 97 blood samples. Of these, 41% had triple mutations at
      the dhfr-gene (at codons 51, 59 and 108), and 15% had triple mutations plus
      mutation at codon 437 in the dhps-gene. Only 45% harboured the wild-type dhfr
      gene. Thus both bacterial resistance and mutations in the parasitic genes were
      common, but not linked in the individual child. As sulphadoxine-pyrimethamine has
      only been used as a second line treatment for chloroquine resistant malaria in
      Guinea-Bissau for a few years, it is worrying to find a high prevalence of
      mutations in the parasitic genes coding for resistance to these drugs. Therefore,
      restricting the use of sulphadoxine-pyrimethamine for the treatment of
      chloroquine resistant malaria might not be sufficient to prevent the development
      of resistance in the parasites as long as antifolate drugs are used extensively.

PMID- 14728623
TI  - Lay diagnosis of causes of death for monitoring AIDS mortality in Addis Ababa,
      Ethiopia.
AB  - Lay diagnoses of death collected at burial sites were validated against two 'gold
      standards': the hospital discharge diagnosis of causes of death obtained by a
      surveillance of hospital deaths (including autopsy results) and the physician
      review of verbal autopsies (VAs) that were carried out for a sample of cemetery
      records. The diagnostic indicators of the lay diagnoses were then used to provide
      estimates of the share of AIDS-attribuTable mortality. The verbal autopsy results
      provide an independent estimate of the percentage of AIDS deaths. From a total of
      21,274 burial records, 2546 hospital discharge diagnoses, 1480 outcomes of
      autopsies and 200 adult verbal autopsies were gathered over a period of 1 year
      starting from February 2001. Independent of the gold standard, lay diagnoses such
      as lung disease and cold have a specificity of about 90% and a combined
      sensitivity of about 55% in determining AIDS mortality. Without a significant
      loss in specificity, the sensitivity increases to 60-65% when diarrhoea, TB,
      herpes zoster and mental or nerve problem are included. We thus conclude that
      even in the presence of a reluctance to talk of HIV/AIDS, lay diagnosis of causes
      of death can be used for monitoring AIDS mortality. Lung disease and cold, in
      particular, have become well-known euphemisms for AIDS in the community. The
      share of AIDS deaths in the adult population (20-54) is estimated at 68%, without
      noticeable differences between men and women. Our results confirm the high impact
      of HIV/AIDS on mortality as was estimated by epidemiological projections for
      Addis Ababa.

PMID- 14728624
TI  - The effect of dementia on outcomes and process of care for Medicare beneficiaries
      admitted with acute myocardial infarction.
AB  - OBJECTIVES: To determine differences in mortality after admission for acute
      myocardial infarction (AMI) and in use of noninvasive and invasive treatments for
      AMI between patients with and without dementia. DESIGN: Retrospective chart
      review. SETTING: Cooperative Cardiovascular Project. PATIENTS: Medicare patients
      admitted for AMI (N=129,092) in 1994 and 1995. MEASUREMENTS: Dementia noted on
      medical chart as history of dementia, Alzheimer's disease, chronic confusion, or
      senility. Outcome measures included mortality at 30 days and 1-year
      postadmission; use of aspirin, beta-blocker, angiotensin-converting enzyme (ACE)
      inhibitor, thrombolytic therapy, cardiac catheterization, coronary angioplasty,
      and cardiac bypass surgery compared by dementia status. RESULTS: Dementia was
      associated with higher mortality at 30 days (relative risk (RR)=1.16, 95%
      confidence interval (CI)=1.09-1.22) and at 1-year postadmission (RR=1.18, 95%
      CI=1.13-1.23). There were few to no differences in the use of aspirin and beta
      blockers between patients with and without a history of dementia. Patients with a
      history of dementia were less likely to receive ACE inhibitors during the stay
      (RR=0.89, 95% CI=0.86-0.93) or at discharge (RR=0.90, 95% CI=0.86-0.95),
      thrombolytic therapy (RR=0.82, 95% CI=0.74-0.90), catheterization (RR=0.51, 95%
      CI=0.47-0.55), coronary angioplasty (RR=0.58, 95% CI=0.51-0.66), and cardiac
      bypass surgery (RR=0.41, 95% CI=0.33-0.50) than patients without a history of
      dementia. CONCLUSION: The results imply that the presence of dementia had a major
      effect on mortality and care patterns for this condition.

PMID- 14728625
TI  - Hormone use and cognitive performance in women of advanced age.
AB  - OBJECTIVES: To explore the association between hormone replacement therapy (HRT)
      and cognitive performance in a group of elderly women (>/=75) using a battery of
      well-standardized neuropsychological instruments. DESIGN: Equivalent samples from
      existing cohort. SETTING: Healthcare provider organization. PARTICIPANTS: All
      women enrolled were participants in an ongoing study of the association between
      HRT and the prevalence and incidence of dementia. Prescription records were used
      to establish HRT status. Fifty-eight users and 47 nonusers of HRT participated in
      this substudy. MEASUREMENTS: Given previous reports that HRT has a positive
      effect on verbal memory, the California Verbal Learning Test and the Logical
      Memory Test were used as primary outcomes. A range of validated tests that assess
      other cognitive domains was also included. RESULTS: There were no significant
      differences between users and nonusers of HRT on any cognitive measures.
      CONCLUSION: Given equivalent groups of users and nonusers of HRT no support was
      found for the hypothesis that use of HRT improves cognitive performance in older
      women.

PMID- 14728626
TI  - The relationship between a dementia diagnosis, chronic illness, medicare
      expenditures, and hospital use.
AB  - OBJECTIVES: To determine whether dementia increases medical expenditures, the
      probability of hospitalization, and potentially preventable hospitalization,
      controlling for variables including age and comorbidity. DESIGN: Cross-sectional
      analysis of 1 year of claims data comparing usage by patients with claims for
      dementia with usage by those without dementia. SETTING: A nationally
      representative 5% random sample of Medicare beneficiaries in 1999. PARTICIPANTS:
      Medicare beneficiaries aged 65 and older with fee-for-service Medicare Parts A
      and B coverage for 1999 (N=1,238,895; dementia patients n=103,512). MEASUREMENTS:
      Per capita expenditures, rate of all-cause hospitalization, rate of preventable
      hospitalization as defined using ambulatory-care sensitive condition (ACSC)
      admissions, and dementia identified using International Classification of
      Diseases, 9th Edition, codes 290, 294, and 331. RESULTS: Prevalence of dementia
      was 8.3%. In a model of expenditures in those who survived the year adjusting for
      age, sex, race, and comorbidity, dementia was associated with an incremental cost
      of 6,927 US dollars, or 3.3 times greater total expenditures than in nondementia
      patients (P<.001), with higher expenditures for each specific type of Medicare
      service. Hospitalization accounted for 54% of adjusted costs. The adjusted odds
      of hospitalization associated with dementia were 3.68 (95% confidence interval
      (CI)=3.62-3.73) and adjusted odds of ACSC hospitalization were 2.40 (95% CI=2.35
      2.46). In those who died, the associations were positive but of smaller
      magnitude. CONCLUSION: In a nationally representative sample, higher Medicare
      expenditures associated with a diagnosis of dementia are in large part due to
      increased hospitalization. Further study is needed into the factors associated
      with high rates of hospitalization in dementia patients including aspects of
      ambulatory management that may be improved.

PMID- 14728627
TI  - Incidence and prevalence of dementia in the Cardiovascular Health Study.
AB  - OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's
      disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study
      (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and
      retrospectively collected data to evaluate dementia. SETTING: Four U.S.
      communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865
      white and 492 African-American participants free of dementia, who completed a
      cranial magnetic resonance image between 1992 and 1994 and were followed for an
      average of 5.4 years. MEASUREMENTS: Dementia was classified by
      neurologist/psychiatrist committee review using neuropsychological tests,
      neurological examinations, medical records, physician questionnaires, and
      proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype
      were collected at baseline. Incidence by type of dementia was determined using
      National Institute of Neurological and Communicative Disorders and Stroke
      Alzheimer's Disease and Related Disorders Association criteria for AD and
      Alzheimer's Disease Diagnostic and Treatment Center's State of California
      criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent
      dementia at entry into the study and 480 incident cases during follow-up.
      Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for
      white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for
      African-American men. Sex differences were not significant within race. Adjusted
      for age and education, racial differences were only of borderline significance
      and may have been influenced by ascertainment methodology. Rates differed
      substantially by educational attainment but were only significant for whites.
      Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4,
      compared with 29.6 for those without this allele (P<.001). In whites, type
      specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates
      were 34.7 and 27.2 for African Americans. At termination of observation, women
      had only a slightly higher prevalence of dementia (16.0%) than men (14.7%).
      CONCLUSION: Sex and racial differences were not found, and VaD was higher than
      reported in other studies. These data provide new estimates of dementia incidence
      in a community sample for projection of future burden.

PMID- 14728628
TI  - Low well-being is an independent predictor for stroke in elderly patients with
      diabetes mellitus.
AB  - OBJECTIVES: To examine whether psychological factors are risk factors for the
      development of stroke in elderly diabetic patients. DESIGN: Prospective cohort
      study. SETTING: Outpatient clinic. PARTICIPANTS: Three hundred seventy-six
      diabetic outpatients free of stroke; mean age 75. METHODS: Well-being and
      diabetes-specific burden were assessed at baseline using the Philadelphia
      Geriatric Center morale scale and the Elderly Diabetes Burden Scale (EDBS),
      respectively. Symptomatic stroke was defined as a focal neurological deficit with
      rapid onset that persists for more than 24 hours, supported by brain computed
      tomography or magnetic resonance imaging. RESULTS: During the 3-year follow-up
      period, 25 symptomatic strokes (24 ischemic strokes and 1 cerebral hemorrhage)
      occurred. Low scores on the morale scale (</=7) were significant predictors for
      stroke after adjustment for age; sex; body mass index; hemoglobin A1c level;
      systolic blood pressure; serum levels of total cholesterol, triglycerides, and
      high-density lipoprotein cholesterol; smoking; and previous ischemic heart
      disease (IHD) (hazard ratio (HR)=3.0, 95% confidence interval (CI)=1.2-7.3,
      P=.017). The relationship between low morale scores and future stroke remained
      significant after adjusting for socioeconomic factors and microalbuminuria.
      Increased symptom burden and social burden, but not dietary restrictions, worry
      about diabetes mellitus (DM), treatment satisfaction, and burden by tablets or
      insulin of EDBS, were also significant predictors for stroke after adjustment for
      age, sex, duration of DM, previous IHD, and microalbuminuria (HR=2.6, 95% CI=1.1
      6.5, P=.039). CONCLUSION: Low well-being and symptom burden were predictors of
      stroke in elderly patients with diabetes mellitus (DM), although the causal
      relationship remains unknown.

PMID- 14728629
TI  - Older adults' views of "successful aging"--how do they compare with researchers'
      definitions?
AB  - OBJECTIVES: To determine whether older adults have thought about aging and aging
      successfully and to compare their perceptions of successful aging with attributes
      of successful aging identified in the published literature. DESIGN: A cross
      sectional, mailed survey. SETTING: King County, Washington. PARTICIPANTS:
      Nondemented participants from two cohorts. The first cohort, referred to as Kame,
      which means turtle, a symbol of longevity for Japanese, enrolled 1,985 Japanese
      Americans aged 65 and older and was established in 1992-94. The second cohort,
      Adult Changes in Thought, enrolled 2,581 white men and women aged 65 and older
      from a health maintenance organization and was established in 1994-96.
      MEASUREMENTS: Respondents were asked whether they had ever thought about aging
      and aging successfully and whether these thoughts had changed over the previous
      20 years and about how important specific attributes, originating from the
      published literature, were in characterizing successful aging. RESULTS: Overall,
      90% had previously thought about aging and aging successfully, and approximately
      60% said their thoughts had changed over the previous 20 years. The Japanese
      American group rated 13 attributes as important to successful aging; the white
      group rated the same 13 as important and added one additional attribute, learning
      new things. CONCLUSION: Older adults' definition of successful aging is
      multidimensional, encompassing physical, functional, psychological, and social
      health. In contrast, none of the published work describing attributes of
      successful aging includes all four dimensions. Future work would benefit from an
      expanded definition to adequately reflect the perceptions of older adults.

PMID- 14728630
TI  - Effect of medical conditions on improvement in self-reported and observed
      functional performance of elders.
AB  - OBJECTIVES: To evaluate the effect of nine disabling medical conditions upon
      recovery from functional limitations by elders. DESIGN: Retrospective analysis of
      prospective longitudinal cohort. SETTING: Community. PARTICIPANTS: Persons aged
      65 and older in Framingham Heart Study. MEASUREMENTS: Change in function in
      elders from biennial Examinations 18 (1983-85; baseline) through 23 (1994-96). At
      each examination, subjects reported limitations in heavy household work, walking
      up and down stairs, walking half a mile, bathing, toileting, and continence. They
      were also directly observed for performance of transferring in and out of a
      chair, dressing, walking 50 feet, and carrying a 10-pound object 10 feet. The
      prevalence of functional limitations and the incidence of recovery from
      functional limitation by the subsequent examination for each task were
      calculated. The effects of congestive heart failure, cognitive impairment,
      diabetes mellitus, stroke, depressive symptoms, hip fracture, knee pain,
      claudication, and chronic obstructive pulmonary disease were evaluated. The
      relationship between the total number of comorbid conditions present (0, 1, 2, 3
      or more), the presence of each individual condition at the start of each
      examination cycle, and the incidence of recovery from functional limitations were
      examined using generalized estimating equations. RESULTS: One thousand eight
      hundred twenty-five subjects were studied at baseline; 1,026 were available 10
      years later. Mean age of subjects at baseline was 73.5 (range 61-95); 60.7% were
      women. The prevalence of functional limitations ranged from 3.1% to 29.8% at
      biennial Examination 18 and increased to 15.1% to 32.4% at Examination 23. The
      incidence of recovery ranged from 3.2% to 78.4% depending upon the task and the
      examination cycle. Increasing disease burden, as measured by the number of
      comorbidities, was associated with a decreased likelihood of recovery from
      functional limitations. Diabetes mellitus, stroke, depressive symptoms, hip
      fracture, and knee pain had the strongest adverse effect upon recovery from
      functional limitations. CONCLUSION: In these community-dwelling elders, recovery
      from prevalent functional limitations was frequent. Increasing disease burden was
      associated with a decreased incidence of recovery. Diabetes mellitus, stroke,
      depressive symptoms, hip fracture, and knee pain had the strongest adverse effect
      on recovery from functional limitations.

PMID- 14728631
TI  - Radiographic resolution of community-acquired bacterial pneumonia in the elderly.
AB  - OBJECTIVES: To investigate the radiographic clearance of proven community
      acquired nontuberculous bacterial pneumonia in nonimmunocompromised older
      patients to provide working estimates of the rate of radiographic resolution as a
      function of the patient cumulative comorbidities, extent of initial radiographic
      involvement, functional status, and causative pathogens. DESIGN: A prospective
      study. PARTICIPANTS: Seventy-four patients aged 70 and older, consecutively
      admitted to a hospital for community-acquired bacterial pneumonia. SETTING: A
      university-affiliated teaching hospital. MEASUREMENTS: Chest radiographs were
      performed every 3 weeks from the date of admission for a total period of 12 weeks
      or until all radiographic abnormalities had resolved or returned to baseline.
      RESULTS: Sixty-four patients (86%) completed the study. The rate of radiographic
      clearance was estimated at 35.1% within 3 weeks, 60.2% within 6 weeks, and 84.2%
      within 12 weeks. Radiographic resolution was significantly slower for those with
      high comorbidity index, bacteremia, multilobar involvement, and enteric gram
      negative bacilli pneumonias. Multivariate regression analysis demonstrated that
      the comorbidity index (relative risk for clearance=0.67 per class index, P<.001)
      and multilobar disease (relative risk for clearance=0.24 for more than one lobe,
      P<.001) had independent predictive value (Cox proportional hazards regression
      model) on the rate of resolution. CONCLUSION: The radiographic resolution of
      nontuberculous bacterial pneumonia in the elderly should take into account the
      extent of lobar disease and the burden of underlying illnesses. A waiting period
      of 12 to 14 weeks is recommended for slowly resolving pneumonia to be considered
      nonresolving.

PMID- 14728632
TI  - Alfacalcidol reduces the number of fallers in a community-dwelling elderly
      population with a minimum calcium intake of more than 500 mg daily.
AB  - OBJECTIVES: To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in
      community-dwelling elderly men and women. DESIGN: Randomized, double-blind,
      placebo-controlled intervention trial. SETTING: Basel, Switzerland. PARTICIPANTS:
      Three hundred seventy-eight community-dwelling elderly (191 women/187 men).
      INTERVENTION: Participants were randomly assigned to receive 1 microg of
      alfacalcidol or matched placebo daily for 36 weeks. MEASUREMENTS: Serum 25
      hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact
      parathormone (iPTH) levels were measured using radioimmunoassay at baseline and
      every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire
      during each study site visit. Dietary calcium intake was assessed at baseline
      using a food frequency questionnaire. RESULTS: At baseline, participants had, on
      average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol
      treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence
      interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by
      medians of total calcium intake, this reduction reached significance in
      alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d
      (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512
      mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also,
      independent of total calcium intake, associated with a significant 37.9%
      reduction in iPTH serum levels (P<.0001). No cases of clinically relevant
      hypercalcemia were observed. CONCLUSION: Provided a minimal calcium intake of
      more than 512 mg/d, alfacalcidol treatment significantly and safely reduces
      number of fallers in an elderly community dwelling population.

PMID- 14728633
TI  - Muscle strength after resistance training is inversely correlated with baseline
      levels of soluble tumor necrosis factor receptors in the oldest old.
AB  - OBJECTIVES: To test the hypothesis that physical exercise induces an
      antiinflammatory response that is associated with reduced chronic activation of
      the tumor necrosis factor (TNF)-alpha system in frail elders and that the
      increase in muscle strength after resistance training is limited by systemic low
      grade inflammation. DESIGN: A 12-week controlled resistance-training study.
      SETTING: Nursing homes in Copenhagen, Denmark. PARTICIPANTS: Twenty-one frail
      nursing home residents aged 86 to 95 completed the study. INTERVENTION: Ten
      participants were randomized to a program of resistance training of knee
      extensors and flexors three times a week for 12 weeks; the remaining 11
      participants served as a control group who joined social activities supervised by
      an occupation therapist. MEASUREMENTS: Muscle strength, plasma levels of TNF
      alpha, soluble TNF receptor (sTNFR)-1, and interleukin (IL)-6 were measured
      before and at the end of the intervention period. RESULTS: The training program
      improved muscle strength but did not affect plasma levels of TNF-alpha and sTNFR
      I or IL-6. However, plasma levels of sTNFR-I at baseline were inversely
      correlated with the increase in muscle strength. CONCLUSION: Low-grade activation
      of the TNF system could limit the increase in muscle strength after resistance
      training in the oldest old. Furthermore, data suggest that the antiinflammatory
      response induced by 12 weeks of resistance training is not sufficient to reduce
      chronic activation of the TNF system, but the small sample size limited this
      interpretation.

PMID- 14728634
TI  - The vulnerability of middle-aged and elderly patients to hepatitis C virus
      infection in a high-prevalence hospital-based hemodialysis setting.
AB  - OBJECTIVES: To determine the relationship between advancing age and the risk of
      acquiring hepatitis C virus (HCV) infection, through evaluation and statistical
      comparison of seroprevalence and seroconversion rates in different age groups of
      patients on long-term hemodialysis (HD). DESIGN: Retrospective cohort study.
      SETTING: Hemodialysis facility of King Fahad Hospital and Tertiary Care Center,
      Al-Hasa region of the eastern province of Saudi Arabia. PARTICIPANTS: One hundred
      ninety-eight patients with end-stage renal disease enrolled for long-term HD
      therapy from September 1995 to September 2000. MEASUREMENTS: HCV seroprevalence
      and seroconversion rates. RESULTS: The overall HCV seroprevalence of 43.4%
      (86/198) and seroconversion rate of 8.6% per year were recorded. Patients aged 55
      to 64 had the highest anti-HCV prevalence (55.3% (26/47)) and annual
      seroconversion rates (11.0%). Those aged 65 to 74 had the next-highest prevalence
      (48.9% (24/49)) and seroconversion rate (9.7%), and patients aged 15 to 24 had
      the lowest prevalence (12.5% (1/8)) and seroconversion rate (2.5%) (reference
      group). CONCLUSION: Significantly higher annual seroconversion rates in those
      aged 55 to 64 and 65 to 74 during a shorter dialysis period (35.6 and 32.7 vs
      58.0 months), suggest the greater susceptibility of the middle-aged and elderly
      patients to acquisition of HCV infection than the younger (15-24 years) group.
      This could be attributed to the combined effect of immunosuppression associated
      with advancing age, uremia, and undernutrition, but multicenter molecular follow
      up studies with larger sample sizes would be needed to corroborate these findings
      and plan appropriate strategies for these high-risk groups.

PMID- 14728635
TI  - Is chronic nonmalignant pain associated with decreased appetite in older adults?
      Preliminary evidence.
AB  - OBJECTIVES: To examine the association between self-reported appetite impairment
      and pain intensity in community-dwelling older adults with chronic nonmalignant
      pain. DESIGN: Cross-sectional survey. SETTING: An outpatient pain clinic at the
      University of Pittsburgh. PARTICIPANTS: A convenience sample of 65 older adults
      with chronic nonmalignant pain. MEASUREMENTS: Demographics, pain intensity (short
      form McGill Pain Questionnaire), self-reported appetite impairment using a newly
      developed instrument, mood (30-item Geriatric Depression Scale, (GDS)), cognitive
      status (Folstein Mini-Mental State Examination), dependence in feeding,
      dependence in grocery shopping and meal preparation, and comorbidities
      (Cumulative Illness Rating Scale). Medication information was classified as total
      number of medications, number of analgesics, number of opioids, and number of
      potential appetite-impairing side effects. RESULTS: Univariate analyses revealed
      that those who reported pain-related appetite impairment had higher pain
      intensity than those who reported no appetite impairment (P<.001). Comparison of
      subjects with and without pain-related appetite impairment revealed a significant
      difference in GDS scores (P=.027), number of analgesics (P=.015), and number of
      opioids (P=.014). None of the other variables was statistically significant. The
      relationship between pain intensity and perceived pain-related appetite
      impairment was maintained in an analysis of covariance that controlled for GDS
      score, number of analgesics, and presence of opioids (P=.004). CONCLUSION:
      Chronic pain is associated with self-reported appetite impairment in older
      adults, but examination of the influence of reduction in pain intensity on
      appetite improvement is needed to establish a causal relationship between chronic
      pain and diminished appetite.

PMID- 14728636
TI  - Subcortical vascular lesions predict functional recovery after rehabilitation in
      patients with L-dopa refractory parkinsonism.
AB  - OBJECTIVES: To identify predictors of functional recovery after an intensive
      rehabilitation training in patients with gait disturbances and refractory
      parkinsonism. DESIGN: Observational study. SETTING: A hospital geriatric
      rehabilitation department ("Ancelle della Carita" hospital of Cremona).
      PARTICIPANTS: Thirty-eight subjects (mean age+/-standard deviation of 78.9+/-6.5;
      66% women) with gait disturbances and L-dopa refractory parkinsonism
      consecutively admitted to a rehabilitation unit within 6 months were recruited.
      Exclusion criteria were obvious musculoskeletal disorders (severe leg arthritis,
      hemiparesis, recent stroke), recent surgery, delirium, physical impairment from
      other identifiable causes, and missing computed tomography (CT) scan. All
      subjects received an intensive standardized rehabilitative program including
      conventional physical therapy and specific gait training. MEASUREMENTS: The
      outcome measure of the rehabilitation training was the gain between admission and
      discharge on the Unified Parkinson Disease Rating Scale (delta-UPDRS). The
      following potential predictors were assessed using comprehensive geriatric
      assessment: physical health (Charlson Comorbidity Index, number of drugs),
      cognitive performance (Mini-Mental State Examination (MMSE)), functional status
      (Tinetti scale), depressive symptoms (Geriatric Depression Scale), nutritional
      status (serum albumin and body mass index), and subcortical cerebrovascular load
      (four classes of increasing severity based on diffuse leukoariosis, patchy
      lesions of the white matter, and lacunas on CT scan). Multivariate logistic
      regression with fixed adjustment for age, cognitive performance, and UPDRS on
      admission and stepwise selection of variables were used to identify independent
      predictors. RESULTS: Patients were divided into two groups of equal size based on
      the delta-UPDRS (high and low functional recovery: delta-UPDRS >8 and </=8,
      respectively). Of all variables, only subcortical cerebrovascular load predicted
      functional recovery at discharge (odds ratio adjusted for age, MMSE, and UPDRS on
      admission=2.3, 95% confidence interval=1.0-5.1). The adjusted proportion of
      patients with high functional recovery decreased with increasing subcortical
      cerebrovascular load: 83%, 61%, 44%, and 27% (adjusted P for trend=0.047).
      CONCLUSION: Subcortical cerebrovascular load is a predicting factor of successful
      rehabilitation in patients with L-dopa refractory parkinsonism.

PMID- 14728637
TI  - Resilience of community-dwelling older persons.
AB  - OBJECTIVES: To assess resilience of community-dwelling older persons using a new
      scale based on response to a stressful life event and to identify the
      demographic, clinical, functional, and psychosocial factors associated with high
      resilience. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Five
      hundred forty-six nondisabled persons aged 70 and older who had experienced a
      stressful life event. MEASUREMENTS: Resilience (as assessed using a simple six
      item scale), demographic factors, chronic conditions, medications, cognitive
      status, grip strength, functional status, physical activity, self-efficacy,
      depressive symptoms, self-rated health, and social support. RESULTS: Participants
      showed a wide range of resilience in response to a stressful event, with a mean
      score+/-standard deviation of 8.9+/-4.0 on an 18-point scale. In bivariate
      analyses, male sex, living with others, high grip strength, independence in
      instrumental activities of daily living (IADLs), having few depressive symptoms,
      and having good to excellent self-rated health were associated with high
      resilience, defined as a score in the best tertile (>10). Independence in IADLs
      (relative risk (RR)=1.36, 95% confidence interval (CI)=1.05-1.69), having few
      depressive symptoms (RR=1.59, 95% CI=1.13-2.11), and good to excellent self-rated
      health (RR=1.38, 95% CI=1.01-1.79) remained independently associated with high
      resilience in multivariate analysis. Depressive symptoms and self-rated health
      remained associated with high resilience after controlling for the perceived
      stressfulness of the event. CONCLUSION: Functional and psychosocial factors are
      associated with high resilience. Further research is needed to determine the
      relationship between resilience and future well-being.

PMID- 14728638
TI  - Subjective memory complaints and objective memory impairment in the Vienna
      Transdanube aging community.
AB  - OBJECTIVES: To help answer the question of whether subjective memory complaints
      are a useful feature in classification systems addressing early stages of
      Alzheimer's disease. DESIGN: A cross-sectional investigation in the context of a
      community-based cohort study. SETTING: Vienna, Transdanube-a geographically
      defined, urban, working-class area. PARTICIPANTS: Three hundred two nondemented
      75-year-olds were examined with regard to subjective memory complaints and
      objective memory performance. The patients were divided into two groups with
      respect to subjective memory complaints and into two groups with respect to
      memory performance on the Fuld Object Memory Evaluation. MEASUREMENTS: The
      percentage of individuals with memory complaints who also had objective memory
      impairment and the percentage of individuals with objective memory impairment who
      also complained about their memory were measured. RESULTS: One-tenth (10.6%) (95%
      confidence interval (CI)=7.7-14.7) of community based sample of 75-year-old
      subjects complained about their memory. There was no difference between
      complainers and noncomplainers with regard to actual memory performance. Only
      6.3% (95% CI=0.16-30.2) of memory-impaired subjects complained about their proven
      memory impairment. CONCLUSION: About 94% (95% CI=69.8-99.8) of memory-impaired
      individuals do not complain about memory problems. Subjective memory complaints
      may not be a useful feature in current diagnostic criteria of mild cognitive
      impairment.

PMID- 14728639
TI  - The effect of short-term estradiol therapy on cognitive function in older men
      receiving hormonal suppression therapy for prostate cancer.
AB  - OBJECTIVES: To determine the effect of estrogen (E) alone (without the influence
      of testosterone (T)) on cognitive function in older men, using 17-beta micronized
      estradiol versus placebo in older men rendered hypogonadal (low T and E) by
      treatment for prostate cancer. DESIGN: Short-term double-blind, randomized,
      controlled trial. SETTING: An outpatient General Clinical Research Center.
      PARTICIPANTS: Twenty-seven community-dwelling men aged 65 and older receiving
      neoadjuvant or established therapy with luteinizing-hormone releasing-hormone
      agonists for treatment of prostate cancer enrolled in a short-term randomized,
      controlled trial of 17-beta micronized estradiol versus placebo on the effect on
      biochemical markers of bone turnover. MEASUREMENTS: Hormone levels, including E,
      T, and sex hormone-binding globulin; standardized neurocognitive tests, including
      measures of sustained attention, executive function, and memory; and
      questionnaires to assess subjects' perception of cognitive deficits and symptoms
      of depression. RESULTS: There were no significant differences between patients
      receiving E or placebo on 15 of 17 neurocognitive measures and no significant
      differences in self-reported cognitive deficits or number of depressive symptoms.
      CONCLUSION: Although studies have suggested that E replacement therapy may
      improve cognitive function, most notably memory performance in postmenopausal
      woman, there was no evidence in the present study that the addition of short-term
      E therapy was more beneficial than placebo in tests of cognitive performance in
      hypogonadal men.

PMID- 14728640
TI  - Clinical phenotype of families with longevity.
AB  - OBJECTIVES: To determine whether offspring of centenarians acquired protection
      from age-related diseases. DESIGN: Case-control study. SETTING: The study was
      part of the Longevity Genes Project at Albert Einstein College of Medicine.
      PARTICIPANTS: Centenarians (n=145), offspring of centenarians (n=180), and
      spouses of the offspring of centenarians (n=75) as a control group. Two
      additional groups served as controls: age-matched Ashkenazi Jews, and an age
      matched control group from the Third National Health and Nutrition Examination
      Survey. MEASUREMENTS: Self-reported family history of longevity; prevalence of
      hypertension, diabetes mellitus, heart attacks, and strokes; and objective
      measurements of body mass index and fat mass. RESULTS: Parents of centenarians
      (born in approximately 1870) had a markedly greater ( approximately sevenfold)
      "risk" for longevity (reaching ages 90-99), supporting the notion that genetics
      contributed to longevity in these families. The offspring of long-lived parents
      had significantly lower prevalence of hypertension (by 23%), diabetes mellitus
      (by 50%), heart attacks (by 60%), and strokes (no events reported) than several
      age-matched control groups. CONCLUSION: Offspring of centenarians may inherit
      significantly better health. The authors suggest that a cohort of these subjects
      and their spouses is ideal to study the phenotype and genotype of longevity and
      its interaction with the environment.

PMID- 14728642
TI  - Taking the next steps in goal ascertainment: a prospective study of patient,
      team, and family perspectives using a comprehensive standardized menu in a
      geriatric assessment and treatment unit.
AB  - OBJECTIVES: To examine the performance of an expanded menu of goals in a
      geriatric rehabilitation setting incorporating patient, family, and team
      perspectives. DESIGN: Prospective comparative study. SETTING: Inpatient geriatric
      rehabilitation unit. PARTICIPANTS: Nineteen consecutive eligible inpatients and
      their family members and seven unit team members. MEASUREMENTS: Each participant
      independently reviewed a standardized menu of medical, functional, psychosocial,
      spiritual, and future planning goals, which were compared with the goals set by
      the healthcare team. RESULTS: On average, patients and their family members
      agreed on goals about half the time; family members tended to have more goals
      than patients. Agreement between the team and patients and families was poor
      (kappas=-0.11-0.33). The team was less likely to identify functional,
      psychosocial, spiritual, and future planning goals. CONCLUSION: Patients and
      families have a broad range of goals that are not always identified by the
      healthcare team. A comprehensive standardized menu is feasible and may be helpful
      in setting goals in a geriatric rehabilitation setting.

PMID- 14728641
TI  - Home hospitalization service for acute uncomplicated first ischemic stroke in
      elderly patients: a randomized trial.
AB  - OBJECTIVES: To evaluate whether home treatment of elderly patients with acute
      uncomplicated first ischemic stroke is associated with different mortality rates
      and clinical outcomes from those of patients treated on a general medical ward
      (GMW). DESIGN: Randomized, controlled, single-blind trial. SETTING: S. Giovanni
      Battista Hospital of Turin. PARTICIPANTS: One hundred twenty elderly patients
      admitted to the emergency department of the hospital with first acute ischemic
      stroke were randomized to home treatment from a geriatric home hospitalization
      service (GHHS) or to GMW treatment. MEASUREMENT: Main outcome was cumulative
      survival at 6 months in the two groups. Residual functional impairment,
      neurological deficit, depression, morbidity, and admission to rehabilitation and
      long-term care facilities were considered as secondary outcomes in survivors.
      RESULTS: One hundred twenty patients (mean age 82; 54 men and 66 women) were
      enrolled (60 in each study arm). The cumulative proportion of cases surviving at
      6 months was 0.65 in the GHHS group and 0.60 in GMW group (log-rank test P=.53).
      Functional and neurological parameters were significantly improved in both GHHS
      and GMW patients, without significant differences between the two groups.
      Depression score was significantly better in home-treated patients (P<.001), who
      were more likely to remain at home at 6 months than hospital-treated patients and
      had a lower rate of select medical complications. CONCLUSION: Home-treated
      elderly patients with ischemic stroke have better depressive scores and lower
      rates of admission to nursing homes. These results should prompt further studies
      to evaluate home hospitalization for elderly stroke patients.

PMID- 14728643
TI  - The identification of seniors at risk screening tool: further evidence of
      concurrent and predictive validity.
AB  - OBJECTIVES: To evaluate the validity of the Identification of Seniors at Risk
      (ISAR) screening tool for detecting severe functional impairment and depression
      and predicting increased depressive symptoms and increased utilization of health
      services. SETTING: Four university-affiliated hospitals in Montreal. DESIGN: Data
      from two previous studies were available: Study 1, in which the ISAR scale was
      developed (n=1,122), and Study 2, in which it was used to identify patients for a
      randomized trial of a nursing intervention (n=1,889 with administrative data, of
      which 520 also had clinical data). PARTICIPANTS: Patients aged 65 and older who
      were to be released from an emergency department (ED). MEASUREMENTS: Baseline
      validation criteria included premorbid functional status in both studies and
      depression in Study 2 only. Increase in depressive symptoms at 4-month follow-up
      was assessed in Study 2. Information on health services utilization during the 5
      months after the ED visit (repeat ED visits and hospitalization in both studies,
      visits to community health centers in Study 2) was available by linkage with
      administrative databases. RESULTS: Estimates of the area under the receiver
      operating characteristic curve (AUC) for concurrent validity of the ISAR scale
      for severe functional impairment and depression ranged from 0.65 to 0.86.
      Estimates of the AUC for predictive validity for increased depressive symptoms
      and high utilization of health services ranged from 0.61 to 0.71. CONCLUSION: The
      ISAR scale has acceptable to excellent concurrent and predictive validity for a
      variety of outcomes, including clinical measures and utilization of health
      services.

PMID- 14728644
TI  - Progress in elder abuse screening and assessment instruments.
AB  - The responsibility of identifying elder mistreatment (EM) often falls on the
      healthcare professional. Many different screening and assessment instruments have
      been developed to aid healthcare professionals in making determinations about EM.
      The purpose of this article is to review existing EM screening and assessment
      instruments to examine progress in this field. The value and limitations of these
      instruments with regard to their use in different clinical and healthcare
      settings are discussed. The settings in which EM screening and assessment are
      conducted are also considered. The authors conclude that there is much to be done
      in terms of achieving consensus on what constitutes an appropriate screen or
      assessment instrument for detecting EM. Effort must be focused on instruments
      that can be used for brief, rapid screenings and those that can be used for more
      detailed diagnostic assessments.

PMID- 14728645
TI  - Ethics reporting in publications about research with Alzheimer's disease
      patients.
AB  - Persons with impaired decision-making capacity require special ethical
      protections during recruitment for and participation in research. To assess how
      fully basic protections for these persons were reported in the literature, the
      first structured review of a sample of reports of trials including Alzheimer's
      subjects was performed in 62 journals between January 1992 and December 1998.
      Neither institutional review board review nor informed consent was mentioned in
      28% of the studies. In 48% of the studies, there was no mention of subject
      involvement in the consent process or that any potential subjects refused or
      withdrew. Protections may have been offered and simply not reported in the
      journal articles. The critical importance of these protections would be
      demonstrated if editors required that authors provide full documentation of
      ethical protections when submitting an article for review. These might be briefly
      reported in the articles but be made available electronically to interested
      readers. Authors could then specify in detail how they conducted their research
      involving persons with diminished decision-making capacity.

PMID- 14728646
TI  - When are you sure that you are wrong? How to exclude a pulmonary embolism.

PMID- 14728647
TI  - Quantity versus quality of life: how do we decide?

PMID- 14728648
TI  - Estrogen and cognition: a true relationship?

PMID- 14728650
TI  - Squamous cell carcinoma arising in long-standing lichen sclerosus et atrophicus.

PMID- 14728651
TI  - Splenic hematoma as a complication of colonoscopy.

PMID- 14728652
TI  - Validity, reliability, and responsiveness of the chronic heart failure
      questionnaire (Chinese version).

PMID- 14728653
TI  - Use of foot veins to monitor hydration in the elderly.

PMID- 14728654
TI  - Low total protein increases injury risk in the elderly.

PMID- 14728655
TI  - An unusual cause of orthostatic hypotension in an older person.

PMID- 14728656
TI  - How old is too old to start dialysis?

PMID- 14728657
TI  - Association between homocysteine, depression, and cognitive function in community
      dwelling older women from Australia.

PMID- 14728658
TI  - Preventing disability through community-based health coaching.

PMID- 14728659
TI  - A "painful" epidural analgesia.

PMID- 14728661
TI  - The unique mutation in ace-1 giving high insecticide resistance is easily
      detectable in mosquito vectors.
AB  - High insecticide resistance resulting from insensitive acetylcholinesterase
      (AChE) has emerged in mosquitoes. A single mutation (G119S of the ace-1 gene)
      explains this high resistance in Culex pipiens and in Anopheles gambiae. In order
      to provide better documentation of the ace-1 gene and the effect of the G119S
      mutation, we present a three-dimension structure model of AChE, showing that this
      unique substitution is localized in the oxyanion hole, explaining the insecticide
      insensitivity and its interference with the enzyme catalytic functions. As the
      G119S creates a restriction site, a simple PCR test was devised to detect its
      presence in both A. gambiae and C. pipiens, two mosquito species belonging to
      different subfamilies (Culicinae and Anophelinae). It is possibile that this
      mutation also explains the high resistance found in other mosquitoes, and the
      present results indicate that the PCR test detects the G119S mutation in the
      malaria vector A. albimanus. The G119S has thus occurred independently at least
      four times in mosquitoes and this PCR test is probably of broad applicability
      within the Culicidae family.

PMID- 14728662
TI  - Cloning and characterization of a trypsin-encoding cDNA of the human body louse
      Pediculus humanus.
AB  - From a cDNA library of the whole insect, a trypsin gene of Pediculus humanus has
      been cloned and sequenced. The 908 bp clone has an open reading frame of 759 bp,
      which encodes a pre-proenzyme with 253 amino acid residues. A sixteen-residue N
      terminal signal peptide is followed by a twelve-residue activation peptide with
      putative cleavage sites at Gly16 and Tyr28. The deduced amino acid sequence has
      several features typical of trypsin proteases and an overall identity of 35-43%
      with the trypsins of several haematophagous Diptera. The 1.0 kb genomic trypsin
      gene contains three introns of 102, 79 and 80 nucleotides following the codons
      for Gly16, Gln74 and Ala155, respectively. Only a single gene seems to be
      present. In Northern blot analysis, unfed first instar larvae have an identical
      or slightly lower level of trypsin mRNA than fed adult lice, and in adults 2-24 h
      after the bloodmeal this gene shows a constitutive expression. After in vitro
      transcription and translation, the activation peptide is cleaved by chymotrypsin,
      a so far unreported phenomenon in trypsin activation.

PMID- 14728663
TI  - Bacterial challenge stimulates innate immune responses in extra-embryonic tissues
      of tobacco hornworm eggs.
AB  - Innate immunity protects juvenile and adult vertebrates and invertebrates against
      potential pathogens; however, it is unknown when developing embryos become immune
      competent and just how they are guarded from infection. To address these
      questions, we studied the effect of immune challenge on early stage eggs of the
      tobacco hornworm, Manduca sexta. We detected many immune-related proteins and
      mRNAs in naive eggs. Upon immune challenge, antimicrobial protein genes were up
      regulated, and antibacterial activity increased. Antimicrobial protein mRNAs and
      lysozyme were present in the extra-embryonic tissues of immune-challenged eggs;
      in addition, melanization in response to bacteria occurred in the yolk but not
      embryonic tissues. We conclude that the extra-embryonic tissues of early stage M.
      sexta eggs are immune competent and likely protect the developing embryo from
      infection. We suggest that innate immune responses of extra-embryonic tissues may
      be a common mechanism for protecting early embryos.

PMID- 14728664
TI  - An immune responsive factor D-like serine proteinase homologue identified from
      the American dog tick, Dermacentor variabilis.
AB  - A Dermacentor variabilis cDNA encoding a clip-domain serine proteinase homologue
      with glycine replacing the catalytic serine was identified from tick haemocytes.
      The D. variabilis product was most similar to Tachypleus tridentatus haemocyte
      antimicrobial factor D and shared significant homologies with a number of immune
      responsive gene products of arthropods, including insect prophenoloxidase
      activating cofactors. Northern blotting analyses confirmed that the tick serine
      proteinase homologue expression levels were highest in haemocytes, and to lesser
      degrees in ovaries and then salivary glands whereas steady-state levels of
      expression in whole ticks were found to be slightly higher in fed versus unfed
      adults or eggs. Challenge of fed adults by Escherichia coli injection
      demonstrated that transcript abundance was significantly increased above those of
      naive controls in a temporal fashion. Additionally, an apparent orthologue of the
      D. variabilis clip-domain molecule was cloned, and expression detected, from a
      Dermacentor andersoni cell line indicating cross species conservation.

PMID- 14728665
TI  - Characterization of an Aedes aegypti bacterial artificial chromosome (BAC)
      library and chromosomal assignment of BAC clones for physical mapping
      quantitative trait loci that influence Plasmodium susceptibility.
AB  - Previous studies have confirmed a genetic basis for susceptibility of mosquitoes
      to Plasmodium parasites. Here we describe our efforts to characterize a bacterial
      artificial chromosome genomic library for the yellow fever mosquito, Aedes
      aegypti, and to identify BAC clones containing genetic markers that define
      quantitative trait loci (QTL) for Plasmodium gallinaceum susceptibility. This
      library (NDL) was prepared from the Ae. aegypti Liverpool strain and consists of
      50 304 clones arrayed in 384-well microplates. We used PCR analysis with
      oligonucleotide primer pairs specific to 106 genetic markers (as sequence-tagged
      sites or STS) to screen the NDL library. Each STS identified between one and
      thirteen independent clones with an average of 3.3 clones. The average insert
      size was 122 kb and therefore the NDL library provides approximately 7.87-fold
      genome coverage. The availability of the NDL library should greatly facilitate
      physical mapping efforts, including positional cloning of QTL for traits of
      interest such as Plasmodium susceptibility and for whole genome sequence
      determination and assembly.

PMID- 14728666
TI  - Molecular cloning and functional expression of a serotonin receptor from the
      Southern cattle tick, Boophilus microplus (Acari: Ixodidae).
AB  - A full-length cDNA encoding a 5-hydroxytryptamine (5-HT) receptor from the
      Southern cattle tick, Boophilus microplus, was isolated using a strategy based on
      sequence homology among G protein-coupled receptors. The deduced amino acid
      sequence revealed highest identity with Drosophila melanogaster 5HT-dro2A
      (Z11489, 50.8%) and 5HT-dro2B (Z11490, 49.5%) receptors. The receptor was
      transiently expressed in mammalian HEK293 cells, and Western blot analysis showed
      the expected 43.3 kDa band. In these cells, application of 5-HT (10 microm)
      inhibited forskolin-induced cAMP synthesis by 26%. The results indicate that the
      tick receptor is an invertebrate 5-HT1-like receptor that couples to Galphai
      protein.

PMID- 14728667
TI  - Analyses of P-like transposable element sequences from the genome of Anopheles
      gambiae.
AB  - We have identified 50 P element-homologous sequences in the genome of Anopheles
      gambiae by performing homology searches against the public genome database of A.
      gambiae using the canonical P element from Drosophila melanogaster as a query
      sequence. While most of these sequences belong to P subfamilies previously
      described from anopheline mosquitoes, at least four new subfamilies were
      identified. One of these A. gambiae P elements, which we termed AgPLS, was
      analysed in detail. AgPLS consists of three exons and does not have inverted
      terminal repeats. This element retains several of the structural features of
      other P-encoded peptides, such as motifs involved in DNA-protein and protein
      protein interaction, and a motif involved in GTP utilization. Strong sequence and
      structural similarity to functional P elements, a number of nonsynonymous
      substitutions that is smaller than that of synonymous substitutions and the
      presence of putative nuclear localization signals suggest that the A. gambiae
      elements may retain the capacity for transposition or its repression. These
      sequences seem to be most closely related to P elements described from Musca
      domestica and Lucilia cuprina, the only P element hosts known outside the family
      Drosophilidae.

PMID- 14728668
TI  - Purification, cDNA cloning and expression of an insect defensin from the great
      wax moth, Galleria mellonella.
AB  - An insect defensin, named Galleria defensin, was purified from the larval
      haemolymph of Galleria mellonella immunized against E. coli. The peptide was
      composed of forty-three amino acid residues containing six cysteines that might
      be engaged in intramolecular disulphide bridges. The primary structure of
      Galleria defensin shared about 90.7% identity to that of heliomicin, which was an
      insect defensin isolated from Heliothis virescens. The full-length cDNA encoding
      Galleria defensin was cloned from the fat body of the immunized G. mellonella
      larvae. Northern blot analysis revealed that Galleria defensin was expressed not
      only in the fat body but also in the midgut against invading bacteria into
      haemocoel. This is the first report presenting cDNA and expression of an insect
      defensin in the lepidopteran species.

PMID- 14728669
TI  - The transcriptome of adult female Anopheles darlingi salivary glands.
AB  - Anopheles (Nyssorhynchus) darlingi is an important malaria vector in South and
      Central America; however, little is known about molecular aspects of its biology.
      Genomic and proteomic analyses were performed on the salivary gland products of
      Anopheles darlingi. A total of 593 randomly selected, salivary gland-derived
      cDNAs were sequenced and assembled based on their similarities into 288 clusters.
      The putative translated proteins were classified into three categories: (S)
      secretory products, (H) housekeeping products and (U) products with unknown cell
      location and function. Ninety-three clusters encode putative secreted proteins
      and several of them, such as an anophelin, a thrombin inhibitor, apyrases and
      several new members of the D7 protein family, were identified as molecules
      involved in haematophagy. Sugar-feeding related enzymes (alpha-glucosidases and
      alpha-amylase) also were found among the secreted salivary products. Ninety-nine
      clusters encode housekeeping proteins associated with energy metabolism, protein
      synthesis, signal transduction and other cellular functions. Ninety-seven
      clusters encode proteins with no similarity with known proteins. Comparison of
      the sequence divergence of the S and H categories of proteins of An. darlingi and
      An. gambiae revealed that the salivary proteins are less conserved than the
      housekeeping proteins, and therefore are changing at a faster evolutionary rate.
      Tabular and supplementary material containing the cDNA sequences and annotations
      are available at
      http://www.ncbi.nlm.nih.gov/projects/Mosquito/A_darlingi_sialome/

PMID- 14728670
TI  - Development of a new Sindbis virus transducing system and its characterization in
      three Culicine mosquitoes and two Lepidopteran species.
AB  - Alphavirus transducing systems (ATSs) are alphavirus-based tools for expressing
      genes in insects. Here we describe an ATS (5'dsMRE16ic) based entirely on Sindbis
      MRE16 virus. GFP expression was used to characterize alimentary tract infections
      and dissemination in three Culicine and two Lepidopteran species. Following per
      os infection, 5'dsMRE16ic-EGFP efficiently infected Aedes aegypti and Culex
      tritaeniorhynchus, but not Culex pipiens pipiens. Ae. aegypti clearly showed
      accumulation of green fluorescent protein (GFP) in the posterior midgut and
      foregut/midgut junction within 2-3 days postinfection. Following parenteral
      infection of larvae, Bombyx mori had extensive GFP expression in larvae and
      adults, but Manduca sexta larvae were mostly resistant. 5'dsMRE16ic should be a
      valuable tool for gene expression in several important insect species that are
      otherwise difficult to manipulate genetically.

PMID- 14728671
TI  - A group of related cDNAs encoding secreted proteins from Hessian fly [Mayetiola
      destructor (Say)] salivary glands.
AB  - A group of cDNAs has been isolated and characterized from Hessian fly [Mayetiola
      destructor (Say)] salivary glands. Members in this group appear to encode
      proteins with secretion signal peptides at the N-terminals. The mature putative
      proteins are small, basic proteins with calculated molecular weights that ranged
      from 8.5 to 10 kDa, and isoelectric points from 9.92 to 10.90. Sequence analysis
      indicated a strong selection for mutations that generate amino acid changes
      within the coding region. Northern blot analysis revealed that these genes are
      expressed only in the first instar larvae, a critical stage that determines if
      the interaction between a specific Hessian fly biotype and a specific wheat
      cultivar is compatible. Genomic analysis demonstrated that multiple copies of
      similar genes are clustered within a short region on chromosome 2A. This is the
      same arm in which two avirulence genes have been mapped.

PMID- 14728672
TI  - Beta-oxidation of fatty acids. A century of discovery.

PMID- 14728673
TI  - Mitochondrial beta-oxidation.
AB  - Mitochondrial beta-oxidation is a complex pathway involving, in the case of
      saturated straight chain fatty acids of even carbon number, at least 16 proteins
      which are organized into two functional subdomains; one associated with the inner
      face of the inner mitochondrial membrane and the other in the matrix. Overall,
      the pathway is subject to intramitochondrial control at multiple sites. However,
      at least in the liver, carnitine palmitoyl transferase I exerts approximately 80%
      of control over pathway flux under normal conditions. Clearly, when one or more
      enzyme activities are attenuated because of a mutation, the major site of flux
      control will change.

PMID- 14728674
TI  - Genetic defects in fatty acid beta-oxidation and acyl-CoA dehydrogenases.
      Molecular pathogenesis and genotype-phenotype relationships.
AB  - Mitochondrial fatty acid oxidation deficiencies are due to genetic defects in
      enzymes of fatty acid beta-oxidation and transport proteins. Genetic defects have
      been identified in most of the genes where nearly all types of sequence
      variations (mutation types) have been associated with disease. In this paper, we
      will discuss the effects of the various types of sequence variations encountered
      and review current knowledge regarding the genotype-phenotype relationship,
      especially in patients with acyl-CoA dehydrogenase deficiencies where sufficient
      material exists for a meaningful discussion. Because mis-sense sequence
      variations are prevalent in these diseases, we will discuss the implications of
      these types of sequence variations on the processing and folding of mis-sense
      variant proteins. As the prevalent mis-sense variant K304E MCAD protein has been
      studied intensively, the investigations on biogenesis, stability and kinetic
      properties for this variant enzyme will be discussed in detail and used as a
      paradigm for the study of other mis-sense variant proteins. We conclude that the
      total effect of mis-sense sequence variations may comprise an invariable-
      sequence variation specific--effect on the catalytic parameters and a conditional
      effect, which is dependent on cellular, physiological and genetic factors other
      than the sequence variation itself.

PMID- 14728675
TI  - Acyl-CoA dehydrogenases and acyl-CoA oxidases. Structural basis for mechanistic
      similarities and differences.
AB  - Acyl-CoA dehydrogenases and acyl-CoA oxidases are two closely related FAD
      containing enzyme families that are present in mitochondria and peroxisomes,
      respectively. They catalyze the dehydrogenation of acyl-CoA thioesters to the
      corresponding trans-2-enoyl-CoA. This review examines the structure of medium
      chain acyl-CoA dehydrogenase, as a representative of the dehydrogenase family,
      with respect to the catalytic mechanism and its broad chain length specificity.
      Comparing the structures of four other acyl-CoA dehydrogenases provides further
      insights into the structural basis for the substrate specificity of each of these
      enzymes. In addition, the structure of peroxisomal acyl-CoA oxidase II from rat
      liver is compared to that of medium chain acyl-CoA dehydrogenase, and the
      structural basis for their different oxidative half reactions is discussed.

PMID- 14728676
TI  - Acyl-CoA dehydrogenases. A mechanistic overview.
AB  - Acyl-CoA dehydrogenases constitute a family of flavoproteins that catalyze the
      alpha,beta-dehydrogenation of fatty acid acyl-CoA conjugates. While they differ
      widely in their specificity, they share the same basic chemical mechanism of
      alpha,beta-dehydrogenation. Medium chain acyl-CoA dehydrogenase is probably the
      best-studied member of the class and serves as a model for the study of catalytic
      mechanisms. Based on medium chain acyl-CoA dehydrogenase we discuss the main
      factors that bring about catalysis, promote specificity and determine the
      selective transfer of electrons to electron transferring flavoprotein. The
      mechanism of alpha,beta-dehydrogenation is viewed as a process in which the
      substrate alphaC-H and betaC-H bonds are ruptured concertedly, the first hydrogen
      being removed by the active center base Glu376-COO- as an H+, the second being
      transferred as a hydride to the flavin N(5) position. Hereby the pKa of the
      substrate alphaC-H is lowered from > 20 to approximately 8 by the effect of
      specific hydrogen bonds. Concomitantly, the pKa of Glu376-COO- is also raised to
      8-9 due to the decrease in polarity brought about by substrate binding. The
      kinetic sequence of medium chain acyl-CoA dehydrogenase is rather complex and
      involves several intermediates. A prominent one is the molecular complex of
      reduced enzyme with the enoyl-CoA product that is characterized by an intense
      charge transfer absorption and serves as the point of transfer of electrons to
      the electron transferring flavoprotein. These views are also discussed in the
      context of the accompanying paper on the three-dimensional properties of acyl-CoA
      dehydrogenases.

PMID- 14728677
TI  - Fidelity of targeting to chloroplasts is not affected by removal of the
      phosphorylation site from the transit peptide.
AB  - Phosphorylation of the transit peptide of several chloroplast-targeted proteins
      enables the binding of 14-3-3 proteins. The complex that forms, together with
      Hsp70, has been demonstrated to be an intermediate in the chloroplast protein
      import pathway in vitro[May, T. & Soll, J. (2000) Plant Cell 12, 53-63]. In this
      paper we report that mutagenesis (in order to remove the phosphorylation site) of
      the transit peptide of the small subunit of ribulose bisphosphate
      carboxylase/oxygenase did not affect its ability to target green fluorescent
      protein to chloroplasts in vivo. We also found no mistargeting to other
      organelles such as mitochondria. Similar alterations to the transit peptides of
      histidyl- or cysteinyl-tRNA synthetase, which are dual-targeted to chloroplasts
      and mitochondria, had no effect on their ability to target green fluorescent
      protein in vivo. Thus, phosphorylation of the transit peptide is not responsible
      for the specificity of chloroplast import.

PMID- 14728678
TI  - Modified colorimetric assay for uricase activity and a screen for mutant Bacillus
      subtilis uricase genes following StEP mutagenesis.
AB  - This study describes a modified colorimetric assay for uricase activity in
      flexible 96-well microtiter plates using the uricase/uric acid/horseradish
      peroxidase/4-aminoantipyrine/3,5-dichloro-2-hydroxybenzene sulfonate colorimetric
      reaction. The utility of this assay was demonstrated in a screen for mutant
      uricase enzymes derived from the uricase gene of the thermophilic bacterium
      Bacillus subtilis by a modified staggered extension process (StEP) mutagenesis.
      An Escherichia coli library of StEP-derived uricase mutant clones was screened
      yielding two identical active mutant uricase genes. Two motifs conserved in
      eukaryotic and prokaryotic uricases are highly conserved in the mutant uricase.
      The mutant uricase protein was found to exhibit high uricase activity (13.1 U.mg(
      1)). Finally, the modified colorimetric method is much more efficient than the
      conventional ones and greatly reduces assay time from 4 days to less than 20 h.

PMID- 14728679
TI  - Soluble LDL-R are formed by cell surface cleavage in response to phorbol esters.
AB  - A 140-kDa soluble form of the low density lipoprotein (LDL) receptor has been
      isolated from the culture medium of HepG2 cells and a number of other cell types.
      It is produced from the 160-kDa mature LDL receptor by a proteolytic cleavage,
      which is stimulated in the presence of 4beta-phorbol 12-myristate 13-acetate
      (PMA), leading to the release of a soluble fragment that constitutes the bulk of
      the extracellular domain of the LDL receptor. By labeling HepG2 cells with
      [35S]methionine and chasing in the presence of PMA, we demonstrated that up to
      20% of LDL-receptors were released into the medium in a 2-h period.
      Simultaneously, the level of labeled cellular receptors was reduced by 30% in
      those cells treated with PMA compared to untreated cells, as was the total number
      of cell surface LDL-receptors assayed by the binding of 125I-labeled antibody to
      whole cells. To determine if endocytosis was required for cleavage,
      internalization-defective LDL-receptors were created by mutagenesis or deletion
      of the NPXY internalization signal, transfected into Chinese hamster ovary cells,
      and assayed for cleavage in the presence and absence of PMA. Cleavage was
      significantly greater in the case of the mutant receptors than for wild-type
      receptors, both in the absence and presence of PMA. Similar results were seen in
      human skin fibroblasts homozygous for each of the internalization-defective LDL
      receptor phenotypes. LDL receptor cleavage was inhibited by the hydoxamate-based
      inhibitor TAPI, indicating the resemblance of the LDL receptor cleavage mechanism
      to that of other surface released membrane proteins.

PMID- 14728680
TI  - Generation and characterization of functional mutants in the translation
      initiation factor IF1 of Escherichia coli.
AB  - Three protein factors IF1, IF2 and IF3 are involved in the initiation of
      translation in prokaryotes. No clear function has been assigned to the smallest
      of these three factors, IF1. Therefore, to investigate the role of this protein
      in the initiation process in Escherichia coli we have mutated the corresponding
      gene infA. Because IF1 is essential for cell viability and no mutant selection
      has so far been described, the infA gene in a plasmid was mutated by site
      directed mutagenesis in a strain with a chromosomal infA+ gene, followed by
      deletion of this infA+ gene. Using this approach, the six arginine residues of
      IF1 were altered to leucine or aspartate. Another set of plasmid-encoded IF1
      mutants with a cold-sensitive phenotype was collected using localized random
      mutagenesis. All mutants with a mutated infA gene on a plasmid and a deletion of
      the chromosomal infA copy were viable, except for an R65D alteration. Differences
      in growth phenotypes of the mutants were observed in both minimal and rich media.
      Some of the mutated infA genes were successfully recombined into the chromosome
      thereby replacing the wild-type infA+ allele. Several of these recombinants
      showed reduced growth rate and a partial cold-sensitive phenotype. This paper
      presents a collection of IF1 mutants designed for in vivo and in vitro studies on
      the function of IF1.

PMID- 14728681
TI  - Different associational and conformational behaviors between the second and third
      repeat fragments in the tau microtubule-binding domain.
AB  - The third repeat fragment (R3) in the four-repeat microtubule-binding domain of
      the water-soluble tau protein has been considered to play an essential role in
      the protein's filamentous assembly. To clarify the associational and
      conformational features that differentiate R3 from the second repeat, R2, the
      heparin-induced assembly profiles of these peptide fragments were monitored by
      the thioflavin fluorescence method and electron microscopy. The trifluoroethanol
      induced reversible conformational change from a random structure to an alpha
      helical structure, in an aqueous solution, was monitored by CD measurement, and
      the structure of R2 in trifluoroethanol solution was analyzed by a combination of
      two-dimensional 1H-NMR measurements and molecular modeling calculations to
      facilitate comparison with the structure of R3. The speed of R3 assembly was
      remarkably faster than that of R2, in spite of their similar amino acid
      sequences. The averaged NMR conformers of R2 exhibited the whole-spanning alpha
      helical structure. Similar features observed in R2 and R3 conformers in
      trifluoroethanol were that the Leu10-Leu20/Lys20 sequence takes a helical
      structure with the amphipathic-like distribution of the respective side-chains,
      whereas the C-terminal moieties are both flexible. In contrast, a notable
      difference was observed at the N-terminal Val1-Lys6 sequence, namely, a helical
      conformation for R2 and an extended conformation for R3. These conformational
      behaviors would be associated with the different self-aggregation speeds and
      seeding reactions between R2 and R3.

PMID- 14728682
TI  - Isolation and biochemical characterization of two soluble iron(III) reductases
      from Paracoccus denitrificans.
AB  - Two soluble enzymes (FerA and FerB) catalyzing the reduction of a number of
      iron(III) complexes by NADH, were purified to near homogeneity from the
      aerobically grown iron-limited culture of Paracoccus denitrificans using a
      combination of anion-exchange chromatography (Sepharose Q), chromatofocusing
      (Mono P), and gel permeation chromatography (Superose 12). FerA is a monomer with
      a molecular mass of 19 kDa, whereas FerB exhibited a molecular mass of about 55
      kDa and consists of probably two identical subunits. FerA can be classified as an
      NADH:flavin oxidoreductase with a sequential reaction mechanism. It requires the
      addition of FMN or riboflavin for activity on Fe(III) substrates. In these
      reactions, the apparent substrate specificity of FerA seems to stem exclusively
      from different chemical reactivities of Fe(III) compounds with the free reduced
      flavin produced by the enzyme. Observations on reducibility of Fe(III) chelated
      by vicinal dihydroxy ligands support the view that FerA takes part in releasing
      iron from the catechol type siderophores synthesized by P. denitrificans.
      Contrary to FerA, the purified FerB contains a noncovalently bound redox-active
      FAD coenzyme, can utilize NADPH in place of NADH, does not reduce free FMN at an
      appreciable rate, and gives a ping-pong type kinetic pattern with NADH and
      Fe(III)-nitrilotriacetate as substrates. FerB is able to reduce chromate, in
      agreement with the fact that its N-terminus bears a homology to the previously
      described chromate reductase from Pseudomonas putida. Besides this, it also
      readily reduces quinones like ubiquinone-0 (Q0) or unsubstituted p-benzoquinone.

PMID- 14728683
TI  - FTIR spectroscopy shows structural similarities between photosystems II from
      cyanobacteria and spinach.
AB  - Photosystem II (PSII), an essential component of oxygenic photosynthesis, is a
      membrane-bound pigment protein complex found in green plants and cyanobacteria.
      Whereas the molecular structure of cyanobacterial PSII has been resolved with at
      least medium resolution [Zouni, A., Witt, H.-T., Kern, J., Fromme, P., Krauss,
      N., Saenger, W. & Orth, P. (2001) Nature (London) 409, 739-743; Kamiya, N. &
      Shen, J.R. (2003) Proc. Natl Acad. Sci. USA 100, 98-103], the structure of higher
      plant PSII is only known at low resolution. Therefore Fourier transform infrared
      (FTIR) difference spectroscopy was used to compare PSII from both
      Thermosynechococcus elongatus and Synechocystis PCC6803 core complexes with PSII
      enriched membranes from spinach (BBY). FTIR difference spectra of T. elongatus
      core complexes are presented for several different intermediates. As the FTIR
      difference spectra show close similarities among the three species, the
      structural arrangement of cofactors in PSII and their interactions with the
      protein microenvironment during photosynthetic charge separation must be very
      similar in higher plant PSII and cyanobacterial PSII. A structural model of
      higher plant PSII can therefore be predicted from the structure of cyanobacterial
      PSII.

PMID- 14728684
TI  - High level cell-free expression and specific labeling of integral membrane
      proteins.
AB  - We demonstrate the high level expression of integral membrane proteins (IMPs) in
      a cell-free coupled transcription/translation system using a modified Escherichia
      coli S30 extract preparation and an optimized protocol. The expression of the E.
      coli small multidrug transporters EmrE and SugE containing four transmembrane
      segments (TMS), the multidrug transporter TehA with 10 putative TMS, and the
      cysteine transporter YfiK with six putative TMS, were analysed. All IMPs were
      produced at high levels yielding up to 2.7 mg of protein per mL of reaction
      volume. Whilst the vast majority of the synthesized IMPs were precipitated in the
      reaction mixture, the expression of a fluorescent EmrE-sgGFP fusion construct
      showed evidence that a small part of the synthesized protein 'remained soluble
      and this amount could be significantly increased by the addition of E. coli
      lipids into the cell-free reaction. Alternatively, the majority of the
      precipitated IMPs could be solubilized in detergent micelles, and modifications
      to the solubilization procedures yielded proteins that were almost pure. The
      folding induced by formation of the proposed alpha-helical secondary structures
      of the IMPs after solubilization in various micelles was monitored by CD
      spectroscopy. Furthermore, the reconstitution of EmrE, SugE and TehA into
      proteoliposomes was demonstrated by freeze-fracture electron microscopy, and the
      function of EmrE was additionally analysed by the specific transport of ethidium.
      The cell-free expression technique allowed efficient amino acid specific labeling
      of the IMPs with 15N isotopes, and the recording of solution NMR spectra of the
      solubilized EmrE, SugE and YfiK proteins further indicated a correctly folded
      conformation of the proteins.

PMID- 14728685
TI  - Conformational changes of Newcastle disease virus envelope glycoproteins
      triggered by gangliosides.
AB  - We have investigated the conformational changes of Newcastle disease virus (NDV)
      glycoproteins in response to receptor binding, using 1,1-bis(4
      anilino)naphthalene-5,5-disulfonic acid (bis-ANS) as a hydrophobicity-sensitive
      probe. Temperature- and pH-dependent conformational changes were detected in the
      presence of free bovine gangliosides. The fluorescence of bis-ANS was maximal at
      pH 5. The binding of bis-ANS to NDV was not affected by chemicals that denature
      the fusion glycoprotein, such as reducing agents, nor by the presence of
      neuraminidase inhibitors such as N-acetyl neuramicic acid. Gangliosides partially
      inhibited fusion and hemadsorption, but not neuraminidase hemagglutinin
      neuraminidase glycoprotein (HN) activity. A conformational intermediate of HN,
      triggered by the presence of gangliosides acting as receptor mimics, was
      detected. Our results indicate that, upon binding to free gangliosides, HN
      undergoes a certain conformational change that does not affect the fusion
      glycoprotein.

PMID- 14728686
TI  - A specific C-terminal deletion in tropomyosin results in a stronger head-to-tail
      interaction and increased polymerization.
AB  - Tropomyosin is a 284 residue dimeric coiled-coil protein that interacts in a head
      to-tail manner to form linear filaments at low ionic strengths. Polymerization is
      related to tropomyosin's ability to bind actin, and both properties depend on
      intact N- and C-termini as well as alpha-amino acetylation of the N-terminus of
      the muscle protein. Nalpha-acetylation can be mimicked by an N-terminal Ala-Ser
      fusion in recombinant tropomyosin (ASTm) produced in Escherichia coli. Here we
      show that a recombinant tropomyosin fragment, corresponding to the protein's
      first 260 residues plus an Ala-Ser fusion [ASTm(1-260)], polymerizes to a much
      greater extent than the corresponding full-length recombinant protein, despite
      the absence of the C-terminal 24 amino acids. This polymerization is sensitive to
      ionic strength and is greatly reduced by the removal of the N-terminal Ala-Ser
      fusion [nfTm(1-260)]. CD studies show that nonpolymerizable tropomyosin
      fragments, which terminate at position 260 [Tm(167-260) and Tm(143-260)], as well
      as Tm(220-284), are able to interact with ASTm(1-142), a nonpolymerizable N
      terminal fragment, and that the head-to-tail interactions observed for these
      fragment pairs are accompanied by a significant degree of folding of the C
      terminal tropomyosin fragment. These results suggest that the new C-terminus,
      created by the deletion, polymerizes in a manner similar to the full-length
      protein. Head-to-tail binding for fragments terminating at position 260 may be
      explained by the presence of a greater concentration of negatively charged
      residues, while, at the same time, maintaining a conserved pattern of charged and
      hydrophobic residues found in polymerizable tropomyosins from a variety of
      sources.

PMID- 14728687
TI  - Purification and functional characterization of insecticidal sphingomyelinase C
      produced by Bacillus cereus.
AB  - Bacillus cereus isolated from the larvae of Myrmeleon bore was found to secrete
      proteins that paralyze and kill German cockroaches, Blattela germanica, when
      injected. One of these active proteins was purified from the culture broth of B.
      cereus using anion-exchange and gel-filtration chromatography. The purified
      toxin, with a molecular mass of 34 kDa, was identified as sphingomyelinase C (EC
      3.1.4.12) on the basis of its N-terminal and internal amino-acid sequences. A
      recombinant sphingomyelinase C expressed in Escherichia coli was as potent as the
      native protein in killing the cockroaches. Site-directed mutagenesis (His151Ala)
      that inactivated the sphingomyelinase activity also abolished the insecticidal
      activity, suggesting that the rapid insect toxicity of sphingomyelinase C results
      from its phospholipid-degrading activity.

PMID- 14728688
TI  - Development of recombinant inhibitors specific to human kallikrein 2 using phage
      display selected substrates.
AB  - The reactive site loop of serpins undoubtedly defines in part their ability to
      inhibit a particular enzyme. Exchanges in the reactive loop of serpins might
      reassign the targets and modify the serpin-protease interaction kinetics. Based
      on this concept, we have developed a procedure to change the specificity of known
      serpins. First, reactive loops are very good substrates for the target enzymes.
      Therefore, we have used the phage-display technology to select from a
      pentapeptide phage library the best substrates for the human prostate kallikrein
      hK2 [Cloutier, S.M., Chagas, J.R., Mach, J.P., Gygi, C.M., Leisinger, H.J. &
      Deperthes, D. (2002) Eur. J. Biochem. 269, 2747-2754]. Selected substrates were
      then transplanted into the reactive site loop of alpha1-antichymotrypsin to
      generate new variants of this serpin, able to inhibit the serine protease. Thus,
      we have developed some highly specific alpha1-antichymotrypsin variants toward
      human kallikrein 2 which also show high reactivity. These inhibitors might be
      useful to help elucidate the importance of hK2 in prostate cancer progression.

PMID- 14728689
TI  - Photoaffinity labelling of the human GM2-activator protein. Mechanistic insight
      into ganglioside GM2 degradation.
AB  - The GM2-activator protein (GM2AP) is an essential cofactor for the degradation of
      ganglioside GM2 by lysosomal beta-hexosaminidase A. It mediates the interaction
      between the water-soluble exohydrolase and its membrane-bound substrate at the
      lipid-water interphase. Inherited defects in the gene encoding this glycoprotein
      result in a fatal neurological storage disorder, the AB variant of GM2
      gangliosidosis. To elucidate the mode of action of this glycoprotein cofactor, we
      synthesized the two photoaffinity labels [14C]C3-TPD-GM2 and [14C]C7-TPD-GM2.
      Incubation of GM2AP with these substrate analogues and subsequent irradiation led
      to covalent labelling of the protein. After separation of tryptic peptides by
      reverse-phase HPLC, the labelled peptide fractions were analysed by MALDI-TOF and
      sequenced by ESI-Q-TOF mass spectrometry. Both labels were found to be
      specifically photoincorporated into a part of the surface loop comprising
      residues V153-L163, a stretch of amino acids that was previously identified as
      the most flexible region in the crystal structure of the activator. Our results
      provide strong evidence that this loop constitutes the part of the activator
      protein that directly interacts with the ganglioside substrate, suggesting that
      the hydrophobicity and the great structural mobility of this element are crucial
      for the extraction of the membrane-embedded glycolipid, its stabilization inside
      the spacious cavity and its guidance to the enzyme's active site. This study
      demonstrates that the approach of photoaffinity labelling in conjunction with
      accurate mass measurements can provide insight into substrate binding
      interactions that complements structural information.

PMID- 14728690
TI  - Interaction between the 2'-5' oligoadenylate synthetase-like protein p59 OASL and
      the transcriptional repressor methyl CpG-binding protein 1.
AB  - The human 2'-5' oligoadenylate synthetases (OAS) form a conserved family of
      interferon-induced proteins consisting of four genes: OAS1, OAS2, OAS3 and the 2'
      5' oligoadenylate synthetase-like gene (OASL). When activated by double-stranded
      RNA, OAS1-3 polymerize ATP into 2'-5'-linked oligoadenylates; 2'-5'-linked
      oligoadenylates, in turn, activate a latent endoribonuclease that degrades viral
      and cellular RNAs. In contrast, while the p59 OASL protein is highly homologous
      to the OAS family (45% identity), its 350 amino acid N-terminal domain lacks 2'
      5' oligoadenylate synthetase activity. A C-terminal 164 amino acid domain, which
      is 30% homologous to a tandem repeat of ubiquitin, further distinguishes the p59
      OASL protein and suggests that it serves a biological role which is distinct from
      other OAS family members. To dissect the function of p59 OASL, we utilized the
      yeast two-hybrid system to identify interacting proteins. Methyl CpG-binding
      protein 1 (MBD1), which functions as a transcriptional repressor, was identified
      as a strong p59 OASL interactor. Interestingly, like p59 OASL, transcription of
      the MBD1 gene was induced by interferon, indicating that these genes are co
      ordinately regulated. The interaction was confirmed in vitro and in vivo and was
      mapped to the ubiquitin-like domain of p59 OASL. The p59 OASL-MBD1 interaction
      was specific, because p59 OASL did not interact with any of the other MBD family
      members and MBD1 did not interact with OAS1. These findings link the p59 OASL
      with MBD1 transcriptional control in the context of an interferon-stimulated
      cell, and provide the basis for future studies to examine the functional role of
      this interaction.

PMID- 14728691
TI  - TbPDE1, a novel class I phosphodiesterase of Trypanosoma brucei.
AB  - Cyclic nucleotide specific phosphodiesterases (PDEs) are important components of
      all cAMP signalling networks. In humans, 11 different PDE families have been
      identified to date, all of which belong to the class I PDEs. Pharmacologically,
      they have become of great interest as targets for the development of drugs for a
      large variety of clinical conditions. PDEs in parasitic protozoa have not yet
      been extensively investigated, despite their potential as antiparasitic drug
      targets. The current study presents the identification and characterization of a
      novel class I PDE from the parasitic protozoon Trypanosoma brucei, the causative
      agent of human sleeping sickness. This enzyme, TbPDE1, is encoded by a single
      copy gene located on chromosome 10, and it functionally complements PDE-deficient
      strains of Saccharomyces cerevisiae. Its C-terminal catalytic domain shares about
      30% amino acid identity, including all functionally important residues, with the
      catalytic domains of human PDEs. A fragment of TbPDE1 containing the catalytic
      domain could be expressed in active form in Escherichia coli. The recombinant
      enzyme is specific for cAMP, but exhibits a remarkably high Km of > 600 microm
      for this substrate.

PMID- 14728692
TI  - A multi-protein complex containing cold shock domain (Y-box) and polypyrimidine
      tract binding proteins forms on the vascular endothelial growth factor mRNA.
      Potential role in mRNA stabilization.
AB  - Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and
      post-transcriptional regulation plays a major role in VEGF expression. Both the
      5'- and 3'-UTR are required for VEGF post-transcriptional regulation but factors
      binding to functional sequences within the 5'-UTR have not been fully
      characterized. We report here the identification of complexes, binding to the
      VEGFmRNA 5'- and 3'-UTR, that contain cold shock domain (CSD) and polypyrimidine
      tract binding (PTB) RNA binding proteins. Analysis of the CSD/PTB binding sites
      revealed a potential role in VEGF mRNA stability, in both noninduced and induced
      conditions, demonstrating a general stabilizing function. Such a stabilizing
      mechanism had not been reported previously for the VEGF gene. We further found
      that the CSD/PTB-containing complexes are large multiprotein complexes that are
      most likely preformed in solution and we demonstrate that PTB is associated with
      the VEGF mRNA in vivo. Complex formation between CSD proteins and PTB has not
      been reported previously. Analysis of the CSD/PTB RNA binding sites revealed a
      novel CSD protein RNA recognition site and also demonstrated that CSD proteins
      may direct the binding of CSD/PTB complexes. We found the same complexes binding
      to an RNA-stabilizing element of another growth factor gene, suggesting a broader
      functional role for the CSD/PTB complexes. Finally, as the VEGF gene is also
      regulated at the transcriptional level by CSD proteins, we propose a combined
      transcriptional/post-transcriptional role for these proteins in VEGF and other
      growth factor gene regulation.

PMID- 14728693
TI  - Overview: fundamental skin care--protecting the barrier.

PMID- 14728694
TI  - The stratum corneum: structure and function in health and disease.
AB  - Our understanding of the formation, structure, composition, and maturation of the
      stratum corneum (SC) has progressed enormously over the past 30 years. Today,
      there is a growing realization that this structure, while faithfully providing a
      truly magnificent barrier to water loss, is a unique, intricate biosensor that
      responds to environmental challenges and surface trauma by initiating a series of
      biologic processes which rapidly seek to repair the damage and restore barrier
      homeostasis. The detailed ultrastructural, biochemical, and molecular dissection
      of the classic "bricks and mortar" model of the SC has provided insights into the
      basis of dry, scaly skin disorders that range from the cosmetic problems of
      winter xerosis to severe conditions such as psoriasis. With this knowledge comes
      the promise of increasingly functional topical therapies.

PMID- 14728695
TI  - Cleansing without compromise: the impact of cleansers on the skin barrier and the
      technology of mild cleansing.
AB  - Cleanser technology has come a long way from merely cleansing to providing
      mildness and moisturizing benefits as well. It is known that harsh surfactants in
      cleansers can cause damage to skin proteins and lipids, leading to after-wash
      tightness, dryness, barrier damage, irritation, and even itch. In order for
      cleansers to provide skin-care benefits, they first must minimize surfactant
      damage to skin proteins and lipids. Secondly, they must deposit and deliver
      beneficial agents such as occlusives, skin lipids, and humectants under wash
      conditions to improve skin hydration, as well as mechanical and visual
      properties. While all surfactants tend to interact to some degree with lipids,
      their interaction with proteins can vary significantly, depending upon the nature
      of their functional head group. In vitro, ex vivo, and in vivo studies have shown
      that surfactants that cause significant skin irritation interact strongly with
      skin proteins. Based on this understanding, several surfactants and surfactant
      mixtures have been identified as "less irritating" mild surfactants because of
      their diminished interactions with skin proteins. Surfactants that interact
      minimally with both skin lipids and proteins are especially mild. Another factor
      that can aggravate surfactant-induced dryness and irritation is the pH of the
      cleanser. The present authors' recent studies demonstrate that high pH (pH 10)
      solutions, even in the absence of surfactants, can increase stratum corneum (SC)
      swelling and alter lipid rigidity, thereby suggesting that cleansers with neutral
      or acidic pH, close to SC-normal pH 5.5, may be potentially less damaging to the
      skin. Mildness enhancers and moisturizing agents such as lipids, occlusives, and
      humectants minimize damaging interactions between surfactants, and skin proteins
      and lipids, and thereby, reduce skin damage. In addition, these agents play an
      ameliorative role, replenishing the skin lipids lost during the wash period. The
      present review discusses the benefits of such agents and their respective roles
      in improving the overall health of the skin barrier.

PMID- 14728696
TI  - Role of mild cleansing in the management of patient skin.
AB  - Routine everyday care of skin is an essential part of optimal patient management.
      Common problems such as xerosis, dermatitis, eczema, psoriasis, acne, rosacea,
      and photodamage leave the skin vulnerable to external insults, partly as a result
      of varying levels of barrier dysfunction. Cosmetic surgery procedures also
      typically damage the stratum corneum (SC) and leave skin with a very weak barrier
      during recovery phase. Cleansing is an important aspect of any skin care, since
      it not only removes unwanted dirt, soil, and bacteria from skin, but also removes
      dead surface cells, preparing skin to better absorb topically applied
      drugs/medication. Care must be taken to minimize any further weakening of the SC
      barrier during cleansing. Cleansers based on mild synthetic surfactants and/or
      emollients that cause minimal barrier perturbation are ideal for these patients.
      The present paper is a brief review of four clinical trials that evaluated the
      efficacy and compatibility of either mild syndet bars or cleansers in patients
      with atopic dermatitis, acne, rosacea, or patients who had received chemical
      peels or Retin-A(R) (tretinoin) treatment for sustained photodamage.

PMID- 14728697
TI  - Personal cleanser technology and clinical performance.
AB  - Cleansing is essential for health and hygiene. Personal cleansing agents, such as
      soap, one of the earliest to be developed, were initially expected to deliver
      only cleansing benefits, but consumer expectations came with time to encompass
      health and cosmetic benefits. This demand led to the development of an array of
      milder cleansing agents with a broader spectrum of application. Cleansing
      products are sold around the world in different forms such as bars (the most
      widely used), liquids, gels, and creams. The present paper discusses the
      chemistry, formulation, product attributes, and benefits of various types of
      personal wash products.

PMID- 14728698
TI  - Moisturization and skin barrier function.
AB  - Over the past decade, great progress has been made toward elucidating the
      structure and function of the stratum corneum (SC), the outermost layer of the
      epidermis. SC cells (corneocytes) protect against desiccation and environmental
      challenge by regulating water flux and retention. Maintenance of an optimal level
      of hydration by the SC is largely dependent on several factors. First,
      intercellular lamellar lipids, organized predominantly in an orthorhombic gel
      phase, provide an effective barrier to the passage of water through the tissue.
      Secondly, the diffusion path length also retards water loss, since water must
      traverse the tortuous path created by the SC layers and corneocyte envelopes.
      Thirdly, and equally important, is natural moisturizing factor (NMF), a complex
      mixture of low-molecular-weight, water-soluble compounds first formed within the
      corneocytes by degradation of the histidine-rich protein known as filaggrin. Each
      maturation step leading to the formation of an effective moisture barrier-
      including corneocyte strengthening, lipid processing, and NMF generation--is
      influenced by the level of SC hydration. These processes, as well as the final
      step of corneodesmolysis that mediates exfoliation, are often disturbed upon
      environmental challenge, resulting in dry, flaky skin conditions. The present
      paper reviews our current understanding of the biology of the SC, particularly
      its homeostatic mechanisms of hydration.

PMID- 14728699
TI  - Moisturizer technology versus clinical performance.
AB  - The principles of humectancy, emolliency, and occlusion, all central to stratum
      corneum (SC) maintenance, continue to drive the development of novel moisturizing
      technologies. Humectants promote water retention within the SC, whereas
      occlusives generally minimize water loss to the external environment. The
      complementary occlusive activity of emollients contributes to SC hydration as
      well. Moisturization technologies, ranging from face care to hand and body care,
      vary in the types and levels of humectants, emollients (including lipids), and
      occlusives; accordingly, their therapeutic effects differ as well. Emulsification
      of these components into a single formulation-the technologies of which are as
      varied as their individual components-is thought to enhance the aesthetics of the
      moisturizer and its overall moisturization efficiency. The present article
      reviews the current approaches to SC moisturization, increasingly viewed as
      critical to its structural and functional integrity, and to fundamental skin
      care.

PMID- 14728700
TI  - An analysis of cumulative lifetime solar ultraviolet radiation exposure and the
      benefits of daily sun protection.
AB  - Cumulative exposure to ultraviolet radiation (UVR) increases the risk of
      developing skin cancer, particularly squamous cell carcinoma and basal cell
      carcinoma. Thus, the need for protection from the sun is widely advocated, but
      consumers generally associate such protection with the occasional extreme
      exposure and tend to ignore the risk of long-term exposure. In fact, a sun
      exposure model predicts that over a lifetime, a person will receive tens of
      thousands of minimal erythema doses worth of UVR through normal, daily,
      incidental exposure. The cumulative effect of casual sun exposure over the years
      underscores the need for everyday basic UVR protection in which even low level
      (SPF 4-10) sunscreens are shown to offer significant benefit. Analysis shows that
      daily protection can reduce lifetime exposure by 50% or more.

PMID- 14728701
TI  - Cleansing, moisturizing, and sun-protection regimens for normal skin, self
      perceived sensitive skin, and dermatologist-assessed sensitive skin.
AB  - Acquiring or maintaining healthy skin requires a multifunctional approach: mild
      cleansing, moisturizing, and sun protection. The clinical benefits of a daily,
      healthy facial skin-care regimen comprising a mild cleanser and moisturizer were
      evaluated on normal skin, self-perceived sensitive skin, and dermatologist
      assessed sensitive skin for a period of up to 4 weeks. Subjects with normal,
      healthy skin were photographed with a calibrated, high-resolution digital camera,
      and the average improvement in overall health was calculated using image morphing
      and facial averaging techniques, following a 2-week period of product
      application. In a second study that included subjects with self-assessed
      sensitive facial skin, changes in skin hydration, skin dryness, and skin
      sensitivity (determined by means of a lactic acid sting test and subject self
      assessment) were monitored during a 3-week regimen of mild cleansing and
      moisturizing with products designed for sensitive skin. The third study involved
      dermatologist-assessed highly sensitive skin patients (mostly rosacea with an
      atopic background in some cases). These patients underwent a 4-week skin-care
      regimen involving mild cleansing and moisturizing. In all three studies,
      significant improvements in skin health/quality were observed by means of expert
      assessments, instrumental evaluations, and subjective self-assessment.

PMID- 14728702
TI  - A chameleon among the episodic vertigo syndromes: 'migrainous vertigo' or
      'vestibular migraine'.

PMID- 14728703
TI  - Vertigo and dizziness related to migraine: a diagnostic challenge.
AB  - Vertigo and dizziness can be related to migraine in various ways: causally,
      statistically or, quite frequently, just by chance. Migrainous vertigo (MV) is a
      vestibular syndrome caused by migraine and presents with attacks of spontaneous
      or positional vertigo lasting seconds to days and migrainous symptoms during the
      attack. MV is the most common cause of spontaneous recurrent vertigo and is
      presently not included in the International Headache Society classification of
      migraine. Benign paroxysmal positional vertigo (BPPV) and Meniere's disease (MD)
      are statistically related to migraine, but the possible pathogenetic links have
      not been established. Moreover, migraineurs suffer from motion sickness more
      often than controls. Persistent cerebellar symptoms may develop in the course of
      familial hemiplegic migraine. Dizziness may also be due to orthostatic
      hypotension, anxiety disorders or major depression which all have an increased
      prevalence in patients with migraine.

PMID- 14728704
TI  - Periods of cluster headache induced by nitrate therapy and spontaneous remission
      of angina pectoris during active clusters.
AB  - Glyceryl trinitrate (GTN) is known to induce single extra attacks of cluster
      headache (CH) during active cluster periods, most probably via actions of nitric
      oxide (NO). Induction of whole periods of CH by organic nitrates has, however,
      attracted little attention in the literature. We report on eight patients with
      episodic CH and coexistent effort-induced angina pectoris. Cases 1-6 had been
      free of their headaches for many years but got recurrence of CH within a few
      weeks after the administration of long-acting organic nitrates (isosorbide
      dinitrate, isosorbide-5-mononitrate or slow-release GTN) aimed at treating their
      chest pains. These nitrate-induced headache periods were more severe and had a
      longer duration than the previous spontaneous ones. Furthermore, one of the
      subjects and two additional cases experienced a marked reduction of their anginal
      attacks during successive CH periods. Exercise time to effort-induced angina was
      increased in all three patients and one of them revealed a markedly elevated
      threshold for eliciting ischaemic cardiac symptoms by standardized physical
      exercise on a cycle ergometer. We hypothesize whether extra CH periods elicited
      by sustained nitrate therapy and remission of angina pectoris during active
      clusters are caused by central mechanisms involving inhibition of sympathetic
      tone and effects on both cranial vessels and cardiac functions.

PMID- 14728705
TI  - Naratriptan has a selective inhibitory effect on trigeminovascular neurones at
      central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine
      therapy.
AB  - The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are
      also active at 5-HT1A and 5-HT1F receptors. We conducted this series of
      experiments to further elucidate the site of action of naratriptan using a well
      established animal model of trigeminovascular stimulation. Following electrical
      stimulation of the superior sagittal sinus of the cat, single cell responses
      (n=83) were recorded in the trigeminal nucleus caudalis. Most cells (91%) also
      responded to electrical and mechanical stimulation of cutaneous or mucosal facial
      receptive fields. The microiontophoretic application of naratriptan resulted in a
      significant suppression of the response to sagittal sinus stimulation (response
      suppressed by 47 +/- 4%, P<0.001). The effect of naratriptan was significantly
      attenuated by application of either the 5-HT(1B/1D) receptor antagonist GR-127935
      (P<0.001) or the 5-HT1A antagonist WAY-100635 (P<0.05). The response of single
      cells to receptive field stimulation was also suppressed by microiontophoretic
      application of naratriptan, but by only 20 +/- 3%. Intravenous administration of
      naratriptan resulted in a similar selective suppression of sagittal sinus vs.
      receptive field responses in trigeminal neurones. These results indicate that
      naratriptan has a central effect in the trigeminovascular system, selectively
      inhibiting afferent activity in craniovascular neurones, via both 5-HT(1B/1D) and
      5-HT1A receptors.

PMID- 14728706
TI  - Reliability of the nitroglycerin provocative test in the diagnosis of
      neurovascular headaches.
AB  - Nitroglycerin administration provokes spontaneous-like migraine attacks in
      migraine and cluster headache (CH) patients. Nitroglycerin-induced migraine-like
      headache has been used as an experimental model of migraine. In this paper, we
      evaluate the possibility of using the nitroglycerin provocative test (NPT) as a
      supportive measure in the diagnosis of primary neurovascular headaches by
      assessing its reliability on a large population and adopting strict criteria for
      rating the response as positive or negative. Our population consisted of 197
      migraineurs, 42 subjects suffering from cluster headache and 53 healthy controls.
      In migraine without aura, the test sensitivity was 82.1%, specificity 96.2% and
      accuracy 85.5%, while in subjects suffering from migraine with aura, the
      reliability of the NPT was less satisfactory (sensitivity 13.6%, specificity
      96.2% and accuracy 72%). In CH patients tested during the active phase of the
      disease the sensitivity was 80.6%, specificity 100% and accuracy 92.9%. NPT is an
      easy, low-cost and reliable method for supporting the diagnosis of migraine
      without aura and cluster headache.

PMID- 14728707
TI  - Quality of life in paediatric migraine: characterization of age-related effects
      using PedsQL 4.0.
AB  - The aim of this study was to measure quality of life (QOL) across a broad age
      range of paediatric migraine patients. Children and adolescents (n=686) with
      migraine completed the Pediatric Quality of Life Inventory, version 4.0 (PedsQL
      4.0) and a standardized headache assessment at an initial clinic visit. The
      sample size for each PedsQL age group was: age 2-4=21, age 5-7=86, age 8-12=298,
      and age 13-18=281. Mean total score was 72.7 +/- 14.8, significantly less than
      healthy norms (P<0.01). Teens reported lower School Functioning than older and
      young children (P<0.05) and young children reported lower Social Functioning than
      older children and teens (P<0.001). A moderate relation was found between self
      and parent report. Age-related effects on QOL have implications for the
      evaluation and management of migraine in paediatric practice. The self and parent
      report forms of the PedsQL can be used in a practice setting.

PMID- 14728708
TI  - Melatonin secretion is supersensitive to light in migraine.
AB  - The present study examined the sensitivity to light of melatonin (MLT) secretion
      in familial migraine during a headache-free interval. Twelve female patients and
      12 healthy controls were included in the trial. All subjects were studied twice.
      In each session, light exposure (300 lx) or placebo was randomly administered for
      30 min between 00.30 and 01.00 h. Blood was sampled hourly between 20.00 and
      24.00 h, and 02.00 and 04.00 h and every 15 min between 00.30 and 01.30 h. Plasma
      MLT levels were determined by radioimmunoassay. MLT suppression was more marked
      in the migraine group than in the control group [difference of area under curve
      (DeltaAUC)=-53.8 +/- 16.2 vs. 18.5 +/- 12.7 pg/h/ml, P<0.005; maximum of MLT
      suppression (Delta)=-35.7 +/- 10.2 vs. - 6.7 +/- 5.8 pg/ml, P<0.05]. These
      findings show a clear hypersensitivity to light in young female migraineurs
      during the headache-free period.

PMID- 14728709
TI  - Sleep and migraine: an actigraphic study.
AB  - The aim of the study was to evaluate sleep of children with migraine during the
      interictal period and the modifications of sleep which precede, are concomitant
      with, or follow migraine attacks. Eighteen patients with migraine without aura
      were compared with a group of 17 healthy age-matched children. Sleep parameters
      were monitored for two full weeks by means of actigraphs and self-report diaries.
      Headache diaries were also filled out in order to evaluate the occurrence and the
      characteristics of migraine attacks. Fifty-seven attacks were recorded during the
      monitoring period. During the interictal period, sleep parameters of children
      suffering from migraine did not differ from those of controls; only sleep onset
      latency was slightly prolonged in the migraine group. Timing of the attack
      affected nocturnal motor activity which presented the lowest values on the night
      preceding the attack, indicating a decrease in cortical activation during sleep
      preceding migraine attacks. Further studies should clarify if the observed
      reduction in nocturnal motor activity close to the attack is related to
      neurotransmitter imbalance.

PMID- 14728710
TI  - Cluster-like headache: association with cervical syringomyelia and Arnold-Chiari
      malformation.

PMID- 14728711
TI  - A patient with long-lasting attacks of bilateral 'blepharospasm', photophobia,
      lacrimation and rhinorrhoea.

PMID- 14728715
TI  - Left ventricular decompression through a patent foramen ovale in a patient with
      hypertrophic cardiomyopathy: a case report.
AB  - The foramen ovale is considered an unidirectional flap-like valvular structure.
      Yet, it may increase in size and allow a continuous left-to-right shunt in order
      to reduce left ventricular filling pressures. We report the case of a 63-year-old
      woman with hypertrophic cardiomyopathy, referred for percutaneous closure of a
      coexisting secundum atrial septal defect. Before catheterization, however,
      transesophageal echocardiography revealed a continuous left-to-right shunt within
      the atrial septum, thus suggesting the diagnosis of patent foramen ovale with
      stable left-to-right shunt. At catheterization, performed under general
      anesthesia and transesophageal echocardiographic monitoring, left ventricular
      early- and end-diastolic pressures were 2 and 12 mmHg and pulmonary-to-systemic
      flow ratio was 1.4. Provocative maneuvers were not able to reverse the shunt. In
      order to assess the effect of the increased left ventricular preload due to the
      abolition of the shunt, an Amplatzer sizing balloon was inflated for 5 minutes
      across the patent foramen ovale. Diastolic pressures rose up to 5 and 18 mmHg,
      respectively. Such a worsening of left ventricular function suggested us not to
      perform the closure procedure. Transcatheter closure of any interatrial
      communication with stable left-to-right shunt induces an abrupt overload of the
      left ventricle that may cause acute heart failure in patients with coexisting
      left ventricular dysfunction. The hemodynamic evaluation of left ventricular
      function during transient abolition of the shunt is an useful tool in order to
      establish the most correct therapeutic strategy. The closure procedure should not
      be performed if a worsening of left ventricular function occurs.

PMID- 14728716
TI  - Blood flow response to a postural challenge in older men and women.
AB  - BACKGROUND: The purpose of this study was to measure blood flow in the carotid
      and femoral arteries, heart rate and blood pressure in response to postural
      challenge in older adults. A second purpose was to determine if older men and
      women have different cardiovascular responses to a postural challenge such as
      tilt. METHODS: Thirty-seven healthy elderly men and women participated in this
      study (69-82 years old). All subjects had similar physical activity levels.
      Postural challenge was induced by a 60 degrees tilt at the level of the waist.
      Continuous carotid blood flow and femoral blood flow was measured with Doppler
      ultrasound. RESULTS: Carotid blood flow was significantly reduced 17% in both men
      and women immediately after tilt (p < 0.001), and by 3.2% two minutes after tilt
      (p < 0.001). Femoral blood flow decreased 59.4% in men and 61% in women
      immediately after tilt (p < 0.001), and remained significantly decreased two
      minutes after tilt by 21% (p <0.001). Heart rate increased by 15% in men (p <
      0.001), and 26% in women immediately after the tilt (p < 0.001). Heart rate
      returned to resting values within two minutes in both men and women. Response to
      tilt was not significantly related to self-report physical activity levels or to
      six-minute walk time. CONCLUSION: A postural challenge induced larger changes in
      the femoral artery compared to the carotid artery. There were no differences
      between men and women to a tilt table test except for differences in heart rate
      response. There was no difference in the blood flow responses to postural
      challenge with physical activity level or between healthy older men and women.

PMID- 14728717
TI  - N-methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in
      colon cancer cells is associated with loss of adenomatous polyposis coli protein,
      microtubule organization, and telomeric DNA.
AB  - BACKGROUND: Cellular senescence is a state in which mammalian cells enter into an
      irreversible growth arrest and altered biological functions. The senescence
      response in mammalian cells can be elicited by DNA-damaging agents. In the
      present study we report that the DNA-damaging agent N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) is able to induce senescence in the HCT-116 colon cancer
      cell line. RESULTS: Cells treated with lower concentrations of MNNG (0-25 microM)
      for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis;
      however, cells treated with higher concentrations of MNNG (50-100 microM) showed
      a senescence-like G0/G1 phase arrest which was confirmed by increased expression
      of beta-galactosidase, a senescence induced marker. The G2/M phase arrest and
      apoptosis were found to be associated with increased levels of p53 protein, but
      the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels,
      since the p53 protein levels decreased in senescence-like arrested cells. We
      further, determined whether the decreased level of p53 was a transcriptional or a
      translational phenomenon. The results revealed that the decreased level of p53
      protein in senescence-like arrested cells was a transcriptional phenomenon since
      p53 mRNA levels simultaneously decreased after treatment with higher
      concentrations of MNNG. We also examined the effect of MNNG treatment on other
      cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The
      expression levels of these proteins were increased in cells treated with lower
      concentrations of MNNG, which supported the G2/M phase arrest. However, cells
      treated with higher concentrations of MNNG showed decreased levels of these
      proteins, and hence, may not play a role in cell cycle arrest. We then examined a
      possible association of the expression of APC protein and telomeric DNA signals
      with cellular senescence in MNNG-treated cells. We found that protein and mRNA
      levels of APC were drastically reduced in cells treated with higher
      concentrations of MNNG. The loss of APC expression might lead to chromosomal
      instability as well as microtubular disorganization through its dissociation with
      tubulin. In fact, the protein level of alpha-tubulin was also drastically
      decreased in senescence-like arrested cells treated with higher concentrations of
      MNNG. The levels of telomeric DNA also decreased in cells treated with higher
      concentrations of MNNG. CONCLUSIONS: These results suggest that in response to
      DNA alkylation damage the senescence-like arrest of HCT-116 cells was associated
      with decreased levels of APC protein, microtubular organization, and telomeric
      DNA.

PMID- 14728718
TI  - Iron supplements: the quick fix with long-term consequences.
AB  - Co-supplementation of ferrous salts with vitamin C exacerbates oxidative stress
      in the gastrointestinal tract leading to ulceration in healthy individuals,
      exacerbation of chronic gastrointestinal inflammatory diseases and can lead to
      cancer. Reactive oxygen and nitrogen species (RONS) have been ascribed an
      important role in oxidative stress. Redox-active metal ions such as Fe(II) and
      Cu(I) further activate RONS and thus perpetuate their damaging effects. Ascorbic
      acid can exert a pro-oxidant effect by its interaction with metal ions via a
      number of established RONS generating systems which are reviewed here. Further
      studies are required to examine the detrimental effects of nutraceuticals
      especially in chronic inflammatory conditions which co-present with anaemia.

PMID- 14728719
TI  - Unscrambling an egg: protein disaggregation by AAA+ proteins.
AB  - Aprotein quality control system, consisting of molecular chaperones and
      proteases, controls the folding status of proteins and prevents the aggregation
      of misfolded proteins by either refolding or degrading aggregation-prone species.
      During severe stress conditions this protection system can be overwhelmed by high
      substrate load, resulting in the formation of protein aggregates. In such
      emergency situations, Hsp104/ClpB becomes a key player for cell survival, as it
      has the extraordinary capacity to rescue proteins from an aggregated state in
      cooperation with an Hsp70 chaperone system. The ring-forming Hsp104/ClpB
      chaperone belongs to the AAA+ protein superfamily, which in general drives the
      assembly and disassembly of protein complexes by ATP-dependent remodelling of
      protein substrates. A disaggregation activity was also recently attributed to
      other eubacterial AAA+ proteins, while such an activity has not yet been
      identified in mammalian cells. In this review, we report on new insights into the
      mechanism of protein disaggregation by AAA+ proteins, suggesting that these
      chaperones act as molecular crowbars or ratchets.

PMID- 14728721
TI  - Severe symptomatic hyponatremia during citalopram therapy--a case report.
AB  - BACKGROUND: Hyponatremia secondary to the syndrome of inappropriate secretion of
      antidiuretic hormone is an uncommon complication of treatment with the new class
      of antidepressant agents, the selective serotonin reuptake inhibitors. The risk
      of hyponatremia seems to be highest during the first weeks of treatment
      particularly, in elderly females and in patients with a lower body weight. CASE
      PRESENTATION: A 61-year-old diabetic male was admitted to the hospital because of
      malaise, progressive confusion, and a tonic/clonic seizure two weeks after
      starting citalopram, 20 mg/day. On physical examination the patient was euvolemic
      and had no evidence of malignancy, cardiac, renal, hepatic, adrenal or thyroid
      disease. Laboratory tests results revealed hyponatremia, serum hypoosmolality,
      urine hyperosmolarity, and an elevated urine sodium concentration, leading to the
      diagnosis of inappropriate secretion of antidiuretic hormone. Citalopram was
      discontinued and fluid restriction was instituted. The patient was discharged
      after serum sodium increased from 124 mmol/L to 134 mmol/L. Two weeks after
      discharge the patient denied any new seizures, confusion or malaise. At that time
      his serum sodium was 135 mmol/L. CONCLUSIONS: Because the use of serotonin
      reuptake inhibitors is becoming more popular among elderly depressed patients the
      present paper and other reported cases emphasize the need of greater awareness of
      the development of this serious complication and suggest that sodium serum levels
      should be monitored closely in elderly patients during treatment with citalopram.

PMID- 14728720
TI  - Exercise increases endostatin in circulation of healthy volunteers.
AB  - BACKGROUND: Physical inactivity increases the risk of atherosclerosis. However,
      the molecular mechanisms of this relation are poorly understood. A recent report
      indicates that endostatin, an endogenous angiostatic factor, inhibits the
      progression of atherosclerosis, and suggests that reducing intimal and
      atherosclerotic plaque tissue neovascularization can inhibit the progression
      atherosclerosis in animal models. We hypothesize that exercise can elevate the
      circulatory endostatin level. Hence, exercise can protect against one of the
      mechanisms of atherosclerosis. RESULTS: We examined treadmill exercise tests in
      healthy volunteers to determine the effect of exercise on plasma levels of
      endostatin and other angiogenic regulators. Oxygen consumption (VO2) was
      calculated. Plasma levels of endostatin, vascular endothelial growth factor
      (VEGF), and basic fibroblast growth factor (bFGF) were determined using ELISA.
      The total peak VO2 (L) in 7 male subjects was 29.5 +/- 17.8 over a 4-10 minute
      interval of exercise. Basal plasma levels of endostatin (immediately before
      exercise) were 20.3 +/- 3.2 pg/ml, the plasma levels increased to 29.3 +/- 4.2,
      35.2 +/- 1.8, and 27.1 +/- 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after
      exercise. There was a strong linear correlation between increased plasma levels
      of endostatin (%) and the total peak VO2 (L) related to exercise (R2 = 0.9388; P
      < 0.01). Concurrently, VEGF levels decreased to 28.3 +/- 6.4, 17.6 +/- 2.4, and
      26.5 +/- 12.5 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There were
      no significant changes in plasma bFGF levels in those subjects before and after
      exercise. CONCLUSIONS: The results suggest that circulating endostatin can be
      significantly increased by exercise in proportion to the peak oxygen consumption
      under physiological conditions in healthy volunteers. These findings may provide
      new insights into the molecular links between physical inactivity and the risk of
      angiogenesis dependent diseases such as atherosclerosis.

PMID- 14728722
TI  - Mobilization of xanthine oxidase from the gastrointestinal tract in acute
      pancreatitis.
AB  - BACKGROUND: Xanthine oxidoreductase has been proposed to play a role in the
      development of local and systemic effects of acute pancreatitis. Under
      physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH)
      but can be converted by proteolytic cleavage to its superoxide-generating form
      xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also
      associated to the polysaccharide chains of proteoglycans on the external
      endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme
      seems to be arising from its mobilization from the gastrointestinal endothelial
      cell surface. Taking into account the ability of alpha-amylase to hydrolyze the
      internal alpha-1,4 linkages of polysaccharides, we wanted to elucidate the
      involvement of alpha-amylase in XDH/XOD mobilization from the gastrointestinal
      endothelial cell surface and the relevance of the ascitic fluid (AF) as the
      source of alpha-amylase in experimental acute pancreatitis. METHODS: Acute
      pancreatitis was induced in male Wistar rats by intraductal administration of 5%
      sodium taurocholate. In another experimental group 3000 U/Kg alpha-amylase was
      i.v. administered. The concentrations of XDH, XOD and alpha-amylase in plasma and
      AF and myeloperoxidase (MPO) in lung have been evaluated. In additional
      experiments, the effect of peritoneal lavage and the absorption of alpha-amylase
      present in the AF by an isolated intestine have been determined. RESULTS: Similar
      increase in XDH+XOD activity in plasma was observed after induction of acute
      pancreatitis and after i.v. administration of alpha-amylase. Nevertheless, the
      conversion from XDH to XOD was only observed in the pancreatitis group. Lung
      inflammation measured as MPO activity was observed only in the pancreatitis
      group. In addition peritoneal lavage prevented the increase in alpha-amylase and
      XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that
      alpha-amylase is absorbed from the AF by the intestine. CONCLUSIONS: During the
      early stages of acute pancreatitis, alpha-amylase absorbed from AF through the
      gastrointestinal tract could interfere with the binding of XDH/XOD attached to
      glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its
      oxidase form promoting an increase in circulating XOD that has been reported to
      be one of the mechanisms involved in the triggering of the systemic inflammatory
      process.

PMID- 14728723
TI  - Altered neurological function in mice immunized with early endosome antigen 1.
AB  - BACKGROUND: Autoantibodies directed against the 160 kDa endosome protein early
      endosome antigen 1 (EEA1) are seen in patients with neurological diseases. To
      determine if antibodies to EEA1 have a neuropathological effect, mice from three
      major histocompatibility haplotype backgrounds (H2q, H2b and H2d) were immunized
      with EEA1 (amino acids 82-1411) that was previously shown to contain the target
      EEA1 epitopes. The mice were then subjected to five neuro-behavioural tests: grid
      walking, forelimb strength, open field, reaching and rotarod. RESULTS: The
      immunized SWR/J mice with sustained anti-EEA1 antibodies had significantly
      reduced forelimb strength than the control non-immune mice of the same strain,
      and BALB/CJ immune mice demonstrated significantly more forelimb errors on the
      grid walk test than the control group. CONCLUSIONS: Antibodies to recombinant
      EEA1 in mice may mediate neurological deficits that are consistent with clinical
      features of some humans that spontaneously develop anti-EEA1 autoantibodies.

PMID- 14728724
TI  - Identification of a novel gene family that includes the interferon-inducible
      human genes 6-16 and ISG12.
AB  - BACKGROUND: The human 6-16 and ISG12 genes are transcriptionally upregulated in a
      variety of cell types in response to type I interferon (IFN). The predicted
      products of these genes are small (12.9 and 11.5 kDa respectively), hydrophobic
      proteins that share 36% overall amino acid identity. Gene disruption and over
      expression studies have so far failed to reveal any biochemical or cellular roles
      for these proteins. RESULTS: We have used in silico analyses to identify a novel
      family of genes (the ISG12 gene family) related to both the human 6-16 and ISG12
      genes. Each ISG12 family member codes for a small hydrophobic protein containing
      a conserved ~80 amino-acid motif (the ISG12 motif). So far we have detected 46
      family members in 25 organisms, ranging from unicellular eukaryotes to humans.
      Humans have four ISG12 genes: the 6-16 gene at chromosome 1p35 and three genes
      (ISG12(a), ISG12(b) and ISG12(c)) clustered at chromosome 14q32. Mice have three
      family members (ISG12(a), ISG12(b1) and ISG12(b2)) clustered at chromosome 12F1
      (syntenic with human chromosome 14q32). There does not appear to be a murine 6-16
      gene. On the basis of phylogenetic analyses, genomic organisation and intron
      alignments we suggest that this family has arisen through divergent inter- and
      intra-chromosomal gene duplication events. The transcripts from human and mouse
      genes are detectable, all but two (human ISG12(b) and ISG12(c)) being upregulated
      in response to type I IFN in the cell lines tested. CONCLUSIONS: Members of the
      eukaryotic ISG12 gene family encode a small hydrophobic protein with at least one
      copy of a newly defined motif of approximately 80 amino-acids (the ISG12 motif).
      In higher eukaryotes, many of the genes have acquired a responsiveness to type I
      IFN during evolution suggesting that a role in resisting cellular or
      environmental stress may be a unifying property of all family members. Analysis
      of gene-function in higher eukaryotes is complicated by the possibility of
      functional redundancy between family-members. Genetic studies in organisms (e.g.
      Dictyostelium discoideum) with just one family member so far identified may be
      particularly helpful in this respect.

PMID- 14728725
TI  - Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming
      growth factor beta signaling.
AB  - BACKGROUND: Transforming growth factor-betas (TGF-betas), bone morphogenetic
      proteins (BMPs) and activins are important regulators of developmental cell
      growth and differentiation. Signaling by these factors is mediated chiefly by the
      Smad family of latent transcription factors. RESULTS: There are a large number of
      uncharacterized cDNA clones that code for novel proteins with homology to known
      signaling molecules. We have identified a novel molecule from the HUGE database
      that is related to a previously known molecule, AMSH (associated molecule with
      the SH3 domain of STAM), an adapter shown to be involved in BMP signaling. Both
      of these molecules contain a coiled-coil domain located within the amino-terminus
      region and a JAB (Domain in Jun kinase activation domain binding protein and
      proteasomal subunits) domain at the carboxy-terminus. We show that this novel
      molecule, which we have designated AMSH-2, is widely expressed and its
      overexpression potentiates activation of TGF-beta-dependent promoters.
      Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4,
      interact with AMSH-2. We show that overexpression of AMSH-2 decreases the
      inhibitory effect of Smad7 on TGF-beta signaling. Finally, we demonstrate that
      knocking down AMSH-2 expression by RNA interference decreases the activation of
      3TP-lux reporter in response to TGF-beta. CONCLUSIONS: This report implicates
      AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF
      beta signaling pathway. Our results suggest that this effect could be partially
      explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-beta
      signaling pathway.

PMID- 14728727
TI  - Journal of Circadian Rhythms: 21st-century publishing for 21st-century science.

PMID- 14728728
TI  - Changing paradigm through a genome-based approach to clinical and basic
      immunology.

PMID- 14728726
TI  - Transdisciplinary unifying implications of circadian findings in the 1950s.
AB  - Afew puzzles relating to a small fraction of my endeavors in the 1950s are
      summarized herein, with answers to a few questions of the Editor-in-Chief, to
      suggest that the rules of variability in time complement the rules of genetics as
      a biological variability in space. I advocate to replace truisms such as a
      relative constancy or homeostasis, that have served bioscience very well for very
      long. They were never intended, however, to lower a curtain of ignorance over
      everyday physiology. In raising these curtains, we unveil a range of dynamics,
      resolvable in the data collection and as-one-goes analysis by computers built
      into smaller and smaller devices, for a continued self-surveillance of the normal
      and for an individualized detection of the abnormal. The current medical art
      based on spotchecks interpreted by reference to a time-unqualified normal range
      can become a science of time series with tests relating to the individual in
      inferential statistical terms. This is already doable for the case of blood
      pressure, but eventually should become possible for many other variables
      interpreted today only based on the quicksand of clinical trials on groups. These
      ignore individual differences and hence the individual's needs. Chronomics
      (mapping time structures) with the major aim of quantifying normalcy by dynamic
      reference values for detecting earliest risk elevation, also yields the dividend
      of allowing molecular biology to focus on the normal as well as on the grossly
      abnormal.

PMID- 14728729
TI  - Androgen receptor expression in the rat prostate is down-regulated by dietary
      phytoestrogens.
AB  - BACKGROUND: It is well established that the growth of the prostate gland is a
      hormone-dependent phenomenon involving both androgenic and estrogenic control.
      Proliferation of prostate cells is, at least in part, under control of estrogen
      receptor beta (ER-beta). Phytoestrogens bind ER-beta with high affinity and
      therefore may have antiproliferative effects in the prostate. METHODS: The
      prostates of male Long-Evans rats fed a diet high in phytoestrogens (Phyto-600)
      or very low levels of phytoestrogens (Phyto-free) were analyzed to determine the
      impact of dietary phytoestrogens on prostate weight and androgen receptor (AR)
      expression in the prostate. RESULTS: Dietary phytoestrogens significantly
      decreased post-pubertal prostate weight gain in Phyto-600 vs Phyto-free fed
      males. Additionally, dietary phytoestrogens (Phyto-600) decreased AR expression
      in the prostate as determined by in situ hybridization. CONCLUSIONS: Soy
      phytoestrogens, present in diet, alter prostate growth presumably by binding ER
      beta and subsequently reducing AR expression within the prostate.

PMID- 14728730
TI  - Mite and cockroach proteases activate p44/p42 MAP kinases in human lung
      epithelial cells.
AB  - BACKGROUND: The mechanisms underlying epithelial cell activation by indoor
      inhaled antigens are poorly understood. METHODS: In this study, we investigated
      the role of mitogen-activated protein kinases (MAPKs) in A549 epithelial cells
      upon exposure to antigens of house dust mite (HDMA), German cockroach (GCA), and
      American cockroach (ACA). RESULTS: Each of these antigens induced a significant
      increase in IL-8 levels compared to the medium control. Exposure of A549 cells to
      these antigens induced the phosphorylation of p44/42 MAPKs within 5 minutes,
      which reached a peak at 25 minutes later and reached baseline levels at 1 hour
      after exposure. PD98059, a MEK1 inhibitor, significantly decreased
      phosphorylation of p44/p42 MAPKs and IL-8 production. Exposure of A549 cells with
      antigens, which had been preincubated with different protease inhibitors, also
      resulted in a reduction of both MAPK phosphorylation and IL-8 production.
      CONCLUSION: Thus, proteolytic antigens present in HDMA, GCA and ACA activate the
      p44/42 MAPKs airway epithelial cells, which lead to elevated IL-8 production and
      initiation of the inflammatory cascade.

PMID- 14728744
TI  - Successes and Failures in Telehealth. Proceedings and abstracts of an
      international conference. Brisbane, Australia, 25-26 August 2003.

PMID- 14728745
TI  - A clinical and educational telemedicine link between Bulgaria and Greece.
AB  - During its transition to a market economy, Bulgaria benefited from foreign aid
      provided by Greece. One of the projects was the clinical and educational
      telemedicine link between the Medical University of Varna in Bulgaria and the
      Faculty of Medicine of Aristotle University of Thessaloniki in Greece. This began
      in 1997. In terms of the educational activities, the Bulgarian side of the
      network supports: an electronic classroom equipped with personal workstations,
      multimedia projectors and videoconference facilities; electronic design and
      publishing activities; Web hosting and mail server activities; and satellite
      communications. Communications are via ISDN. The main clinical experience has
      been remote consultations in immunology. This experience (admittedly limited)
      demonstrates that telemedicine can be used to provide assistance to remote
      colleagues. In addition, the use of telemedicine can greatly improve the quality
      of care available to travellers and migrant workers in cases where the patient
      cannot communicate with the attending physician because of a language barrier.

PMID- 14728746
TI  - Developing prison telemedicine systems: the Greek experience.
AB  - Prison telemedicine systems operate in circumstances in which the provision of
      medical care is very expensive. In 1999 the Greek Ministry of Justice decided to
      use telemedicine to improve health services in the largest prison in Greece
      (Korydallos Prison, in Athens). The Nikea Hospital in Piraeus undertook to
      support the effort in order: to enable prison paramedics and guards to call for
      remote evaluation of inmates when the prison's doctors were off duty; to provide
      second opinions; and to allow screening and primary care coverage for inmates
      through teleconsultations with Nikea Hospital specialists. For 12 months
      following installation, intensive 'hands-on' training on the use of the system
      was offered to the staff of both the Korydallos Prison and the Nikea Hospital. In
      all, 400 physicians, nurses and paramedics were trained. Despite all this effort,
      there were serious operational problems related either to prison bureaucracy or
      to the inflexibility of the Greek national health system, which annulled the
      effectiveness of the prison telemedicine system. The experience suggests that
      prison telemedicine is a viable option if freed from bureaucratic and labour
      related obstacles, and can improve the quality of care available to prisoners.

PMID- 14728747
TI  - Implementation of videoconferencing to support a managed clinical network in
      Scotland: lessons learned during the first 18 months.
AB  - Managed clinical networks (MCNs) are usually built on established groups of
      health professionals from both acute and primary care sectors. We have used
      videoconferencing to support the gynaecological oncology MCN in the west of
      Scotland. Videoconferencing was implemented simultaneously at five sites in 2001
      and DICOM image-capture software was added in 2003. Videoconferencing and live PC
      links allowed the multidisciplinary teams to discuss individual cancer diagnoses
      without the extensive travelling previously required. Our experience of the
      implementation suggests that local ownership is crucial. In the present project,
      each of the stakeholders had an important role in the delivery of a successful
      system. High-quality project management is required during implementation and for
      some time thereafter to achieve sustainability.

PMID- 14728748
TI  - Remote critical care consultation: telehealth projection of clinical specialty
      expertise.
AB  - Remote critical care consultations have been employed between the Naval Hospital
      in Guam and the Tripler Army Medical Center in Hawaii, a distance of 5300 km.
      During a 10-week study period there were physician-physician daily consultation
      rounds for patients in the intensive care unit at the Naval Hospital.
      Physiological data, video-images and sound were transmitted via a 768 kbit/s
      frame relay connection, albeit with a 1-3 s delay. During the study there were 87
      consultations concerning 25 patients. Preliminary results showed that a broad
      range of critical care patients could be managed effectively through daily remote
      critical care consultation. Broader implementation of this strategy may represent
      a method of making critical care expertise available to front-line military
      health-care facilities and to remote civilian facilities with limited critical
      care expertise.

PMID- 14728749
TI  - Fetal endoscopic telesurgery using an Internet Protocol connection: clinical and
      technical challenges.
AB  - Until recently, fetoscopic laser surgery to seal the placental anastomoses that
      cause severe twin-to-twin transfusion syndrome has been available in only a few
      centres worldwide. The technique typically takes a long time to learn. We have
      used a dedicated Internet Protocol (IP) connection for tele-education to assist
      the introduction of fetoscopic laser surgery to Australia. During the
      implementation of the international telemedicine link, there were multiple
      clinical and technical problems, which were eventually overcome. The quality of
      images and of video-sequences was comparable to that supported by an ISDN
      connection. Pictures of live surgery performed by an expert in Florida, USA, were
      transmitted and viewed by a novice team in Brisbane, Australia. The Australian
      team has performed 19 fetoscopic laser operations to date. Preliminary results
      are comparable to those from centres that have performed over 100 procedures.

PMID- 14728750
TI  - Telehealth in Western Australia: the challenge of evaluation.
AB  - Between 1996 and 2003, a network of 85 telehealth videoconference sites was
      implemented in Western Australia (WA), together with 19 teleradiology facilities.
      Telehealth services have been growing steadily, and in 2002 there were over
      30,000 teleradiology transmissions and 1250 clinical occasions of service via
      videoconference. The funding bodies, and in particular the WA Department of
      Health, need to know whether the aims of the project have been achieved. They
      must also decide whether investment should continue. A process of progressive
      evaluation has been implemented to identify progress to date, the benefits
      achieved and the potential for further development. However, it is difficult to
      evaluate a broad range of programmes in rural and remote locations for such an
      embryonic service. These difficulties are compounded by the lack of a strategy at
      national level to ensure consistency and compatibility not only of
      infrastructure, equipment and standards but also of data capture and evaluation
      methodologies for telehealth. This would allow comparisons across regions and
      states, which in turn would provide opportunities to learn from others and thus
      improve health-care nationally.

PMID- 14728751
TI  - A tele-otology course for primary care providers.
AB  - The shortage of otolaryngologists and the high incidence of ear disease in remote
      areas are major problems in Australia. We have developed a multimedia course for
      primary care providers that incorporates material about ear anatomy and
      physiology, ear disease, video-otoscopy and telemedicine software. The computer
      based course was followed by a practical one-day course. A multiple-choice test
      was given to participants before and at the end of the course and a form was used
      to record feedback. The course was conducted with 30 aboriginal health workers.
      The participants were able to obtain images of reasonable to good quality after a
      short period of training. There was an average improvement of about 25% in the
      test scores, and the feedback regarding the course was extremely positive. The CD
      ROM and the Website provide a valuable resource to assist primary care providers
      in their care of patients with ear disorders.

PMID- 14728752
TI  - A Web-based approach to low-cost telemedicine.
AB  - We have developed a Web-based application for managing e-consultations. This
      solves some of the problems inherent in peer-to-peer email communication.
      Referrals were from three hospitals in Vietnam. Each hospital was provided with
      Internet access for up to 4 hours a day for an initial 12-month period. In the
      first six months, six doctors from the Vietnamese hospitals submitted a total of
      30 cases. Specialists in Sydney provided their expertise on a voluntary basis.
      Preliminary data suggest that the Vietnamese doctors found the system benefited
      their diagnostic and management decision making. Challenges have included
      equipment failures, language barriers and the difficulty of obtaining feedback.
      Successes have included the relationship building between doctors in the two
      countries. Preliminary results were encouraging and most of the Vietnamese
      doctors (five of the six) reported that they were slowly incorporating use of the
      system into their daily practice.

PMID- 14728753
TI  - Organizational readiness for telemedicine: implications for success and failure.
AB  - The use of telemedicine brings about change in health-care organizations and
      opens up new possibilities for service delivery. The organizational environment
      is often crucial in determining whether or not telemedicine applications will be
      successful. To examine the concept of 'organizational readiness for telemedicine'
      as a factor to explain why telemedicine initiatives succeed or fail, the results
      were used of interviews with key informants, conducted in two studies: the
      Alliance for Building Capacity project and the National Initiative for Telehealth
      guidelines project. The data indicate that organizational readiness for
      telemedicine is a multifaceted concept that is related to planning and the
      workplace environment. A greater understanding of the factors within
      organizational readiness could help to avoid costly implementation errors.
      'Readiness' needs to be systematically assessed and is important for long-term
      success.

PMID- 14728754
TI  - A partnership model for the delivery of health education to rural and remote
      communities using multipoint videoconferencing.
AB  - Multipoint videoconferencing has been used by Women's Health Queensland Wide
      (WHQW) for the delivery of health education to the residents of regional, remote
      and rural Queensland communities. The educational programme was a partnership
      between WHQW and health professionals in the participating communities. Telephone
      interviews with the health professionals were used in a follow-up study. Fifty
      one interviews were conducted in October and November 2002; these involved 43 of
      the 64 participating towns. The results suggested that the project contributed to
      improved social capital in the participating communities. In addition, it gave
      rise to unexpected but valuable outcomes for WHQW and, potentially, for the
      Queensland community. The project demonstrated that success in telehealth can be
      measured in terms of social and community effects, as well as clinical outcomes
      and cost-effectiveness.

PMID- 14728755
TI  - Dermatology education on the Web.
AB  - Conventional dermatology teaching favours a didactic, factual approach, rather
      than a problem-solving approach. A Web-based education system that uses a problem
      solving approach offers many advantages. Several international Websites now
      provide continuing education to specialist dermatologists. These are all
      'discretionary' Websites, that is, they are visited by choice; 'obligatory'
      educational Websites are those tied to a university medical faculty or
      postgraduate college and which host either online tasks that must be completed or
      unique examinable material. An interactive education Website, named Dermconsult,
      has been established unofficially for fellows of the Australasian College of
      Dermatologists and registrars in training. However, a successful Website will
      require backing from certifying organizations. Continuing medical education will
      need to be compulsory for potential users if an educational Website is to be
      successful.

PMID- 14728756
TI  - Managing risk in telemedicine.
AB  - Whenever something novel is introduced there are problems of implementation and
      operation, which may be formally expressed as risks. A comprehensive methodology
      has been developed to assess these risks, but it has not yet been extensively
      applied in the health sector. Until now, health has appropriately concentrated on
      the detection and reduction of clinical incidents in established services.
      However, there is strategic value in looking more broadly at the process of risk
      management. This is relevant to risk management in telemedicine.

PMID- 14728757
TI  - Can telepharmacy provide pharmacy services in the bush?
AB  - Rural and remote community pharmacies service large areas of rural Queensland,
      and because of the distances involved often do not meet the patients for whom
      they provide medication. Telepharmacy would improve the quality of pharmaceutical
      services provided in rural and remote areas, by allowing community pharmacists to
      have realtime contact with dispensing doctors, aboriginal health workers and
      patients via a video-phone. We used commercial (analogue) videophones to connect
      community pharmacists to dispensing doctors, patients in depot pharmacies (i.e.
      those with no pharmacist) and aboriginal health workers. However, various
      problems occurred and only 10 video-phone interactions were recorded during the
      six-month project. In all of the recorded interactions, the video-phone was
      actually used as a conventional telephone because a video-connection could not be
      established at the time of the call. (This may have been due to telephone network
      problems in the rural areas.) Despite these problems, all project participants
      showed great enthusiasm for the potential benefits of such a service.

PMID- 14728758
TI  - Teleneurology by email.
AB  - We introduced an email teleneurology service for patients referred to a
      neurologist by general practitioners. Over 14 months, 76 referrals (of 75
      patients) were received. To determine the sustainability of the service, we
      studied a second cohort of 76 consecutive patients referred after our first
      study. We also followed up the first cohort of patients to get information on
      longer-term safety. The second cohort was obtained in one month less than the
      first, and had similar characteristics in terms of age, sex and the time taken by
      the neurologist to reply to the general practitioner. It contained fewer patients
      requiring clinic appointments (34% versus 43%). Fewer patients from the second
      cohort were referred for second opinions (4 versus 10) and there were no
      resulting changes in diagnosis. Follow-up of the first cohort from a mean of 6
      months to a mean of 23 months led to seven more re-referrals and no additional
      changes in diagnosis. We conclude that teleneurology by email is sustainable for
      this group of patients, and confirm that it is safe, effective and efficient.

PMID- 14728759
TI  - Low-bandwidth telerehabilitation for patients who have undergone total knee
      replacement: preliminary results.
AB  - We have developed a low-bandwidth, Internet-based telerehabilitation system to
      provide outpatient rehabilitation to patients who have undergone total knee
      arthroplasty. The preliminary efficacy of this treatment programme in terms of
      both physical and functional objective outcome measures was assessed on 21
      patients. Subjects receiving a six-week rehabilitation programme were randomized
      to the telerehabilitation system or the usual face-to-face method. The physical
      and functional improvements in the telerehabilitation group were similar to those
      in the control group. There was a non-significant trend for greater improvements
      in the telerehabilitation group for most outcome measurements. The
      telerehabilitation programme was well received by patients. The results of this
      study provide evidence for the efficacy of low-bandwidth telerehabilitation
      consultations.

PMID- 14728760
TI  - The diagnostic reliability of Internet-based observational kinematic gait
      analysis.
AB  - We investigated the accuracy and reliability of observational kinematic gait
      assessments performed via a low-bandwidth Internet link (18 kbit/s) and a higher
      speed Internet link (128 kbit/s). Twenty-four subjects were randomized to either
      bandwidth group. Gait was assessed with the Gait Assessment Rating Scale (GARS)
      in the traditional manner, which is from video-recordings, and with repeated
      measurements via the online method. Online assessment was found to provide as
      accurate a measure of gait performance as the traditional assessment (limits of
      agreement<1 GARS point; intraclass correlation coefficient, ICC = 0.96)
      regardless of the speed of the Internet connection. The online assessment also
      demonstrated high intra-rater (ICC = 0.96) and inter-rater (ICC = 0.92)
      reliability. Low-bandwidth telerehabilitation applications appear to be feasible
      via the Internet.

PMID- 14728761
TI  - Video-phone communication with cognitively impaired elderly patients.
AB  - We investigated the potential role of remote interactions via video-phone in the
      care of the elderly. Family members and nursing staff were interviewed about
      their experiences of communicating with elderly people via video-phone. Seven
      family members and seven nursing staff participated in the studies. The
      interviews were analysed using qualitative content analysis. The results showed
      that it was possible for elderly people with cognitive impairment to engage in
      remote communication when certain conditions were met. There were also
      indications that the video-phone interaction sometimes increased the attention
      and focus of the elderly subjects.

PMID- 14728762
TI  - The use of online health techniques to assist with the delivery of specialist
      paediatric diabetes services in Queensland.
AB  - We have tested an alternative method of delivering health services to regional
      areas of Queensland. By integrating telepaediatrics into an existing outreach
      programme for children with diabetes and endocrine conditions, we were able to
      reduce travel for specialist hospital staff while maintaining (and sometimes
      increasing) the contact patients had with the specialist team. In the first 28
      months, we facilitated 160 patient consultations and 10 education sessions via
      videoconference through the telepaediatric service. By the end of the study, site
      visits were taking place annually and routine videoconference clinics were
      scheduled quarterly for the review of new patients and follow-up. Telepaediatric
      services in endocrinology and diabetes were established at three levels: the
      coordination of routine specialist clinics via videoconference; ad hoc patient
      consultations for collaborative management during acute presentations and at
      times of urgent clinical need; and the delivery of education to staff and
      patients throughout the state. The net result was improved access to specialist
      services from rural and remote areas of Queensland.

PMID- 14728763
TI  - The family costs of attending hospital outpatient appointments via
      videoconference and in person.
AB  - We compared the costs incurred by families attending outpatient appointments at
      the Royal Children's Hospital (RCH) in Brisbane with those incurred by families
      who had a consultation via videoconference in their regional area. In each
      category 200 families were interviewed. The median time spent travelling for
      videoconferences was 30 min compared with 80 min for face-to-face appointments.
      Families interviewed in the outpatient department had travelled a median distance
      of 70 km, while those who had a videoconference at the local hospital had
      travelled only 20 km. It cost these families much more to attend an appointment
      at the RCH than to attend a videoconference. Ninety-six per cent of families
      (193) reported at least one of the following types of expense: 150 families had
      expenses related to parking (median A 10 dollars), 156 had fuel expenses (median
      A 10 dollars) and 122 reported costs related to meals purchased at the RCH
      (median A 10 dollars). Only 21 families who had their appointment via local
      videoconference reported any additional costs. Specialist appointments via
      videoconference were a more convenient and cheaper option for families living in
      regional areas of Queensland than the conventional method of attending outpatient
      appointments at the specialist hospital in Brisbane.

PMID- 14728764
TI  - Benefit for the patient of a teleradiology process certified to meet an
      international standard.
AB  - To guarantee the quality of teleradiology services in Austria we have developed
      an easy-to-use and continuously re-evaluated teleradiology workflow model. This
      is based on the quality management model (ISO 9001:2000) of the International
      Standardization Organization (ISO) and guarantees the quality of the process.
      From January 2002 to January 2003 we examined 544 emergency teleradiology
      computerized tomography studies transmitted to the Department of Radiology 2 in
      Innsbruck. The patients were from the rural hospital of Reutte. In 450 cases
      (83%) the sending of the written legal final report took less than 1 h. The
      numbers of mistakes (mostly minor workflow errors) were reduced from 23 errors
      per month in January 2002 to 9 errors per month in January 2003. The continuous
      cross-checking of the workflow and the training of the employees involved
      guaranteed a better standard of teleradiology in our department. Since December
      2002, the whole Tyrolean teleradiology process has been ISO 9001:2000 certified.

PMID- 14728765
TI  - A review of the first year's experience with an automatic message-routing system
      for low-cost telemedicine.
AB  - The Swinfen Charitable Trust has used email for some years as a low-cost
      telemedicine medium to provide consultant support for doctors in developing
      countries. A scalable, automatic message-routing system was constructed which
      automates many of the tasks involved in message handling. During the first 12
      months of its use, 1510 messages were processed automatically. There were 128
      referrals from 18 hospitals in nine countries. Of these 128 queries, 89 (70%)
      were replied to within 72 h; the median delay was 1.1 day. The 39 unanswered
      queries were sent to backup specialists for reply and 36 of them (92%) were
      replied to within 72 h. In the remaining three cases, a second-line (backup)
      specialist was required. The referrals were handled by 54 volunteer specialists
      from a panel of over 70. Two system operators, located 10 time zones apart,
      managed the system. The median time from receipt of a new referral to its
      allocation to a specialist was 0.2 days (interquartile range, IQR, 0.1-0.8). The
      median interval between receipt of a new referral and first reply was 2.6 days
      (IQR 0.8-5.9). Automatic message handling solves many of the problems of manual
      email telemedicine systems and represents a potentially scalable way of doing low
      cost telemedicine in the developing world.

PMID- 14728767
TI  - Interactive nursing skills training using advanced networked technology.
AB  - We have developed a Web-based e-learning tool for teaching nursing skills, using
      educational material from a hospital-based nursing skills 'fair'. Management
      software was used to track skill certification and continuing education contact
      hours. The content could be delivered over the Internet and through firewalls
      using Windows Media Player version 9. The content was structured in a manner that
      made it adaptable to an e-learning system that used the Sharable Content Object
      Reference Model (SCORM), a set of specifications for delivering educational
      materials through technology-based methods.

PMID- 14728766
TI  - Assessment of motor speech disorders online: a pilot study.
AB  - We have conducted a preliminary validation of an Internet-based telehealth
      application for assessing motor speech disorders in adults with acquired
      neurological impairment. The videoconferencing module used NetMeeting software to
      provide realtime videoconferencing through a 128 kbit/s Internet link, as well as
      the transfer of store-and-forward video and audio data from the participant to
      the clinician. Ten participants with dysarthria following acquired brain injury
      were included in the study. An assessment of the overall severity of the speech
      disturbance was made for each participant face to face (FTF) and in the online
      environment; in addition, a 23-item version of the Frenchay Dysarthria Assessment
      (FDA) (which measures motor speech function) and the Assessment of
      Intelligibility of Dysarthric Speech (ASSIDS) (which gives the percentage word
      and sentence intelligibility, words per minute and a rating of communication
      efficiency) were administered in both environments. There was a 90% level of
      agreement between the two assessment environments for the rating of overall
      severity of dysarthria. A 70-100% level of agreement was achieved for 17 (74%) of
      the 23 FDA variables. On the ASSIDS there was a significant difference between
      the FTF and online assessments only for percentage word intelligibility. These
      findings suggest that Internet-based assessment has potential as a reliable
      method for assessing motor speech disorders.

PMID- 14728768
TI  - International medical education between Hawaii and Thailand over Internet2.
AB  - International medical education sessions have been successfully conducted by
      videoconferencing using Internet2. The sessions were between two tertiary care
      medical centres, in Honolulu and Bangkok. However, video quality was lower than
      for similar sessions using ISDN and audience satisfaction was less. The main
      reasons for the lower quality were network congestion and bandwidth allocation by
      the videoconferencing equipment. Software to ensure quality of service is
      available, but is not easy to implement. There were also network security
      problems and the costs were high. Our international videoconferences averaged 40
      50 hours per year, an activity level at which connection costs were lower for
      ISDN than for Internet2. It appears that Internet2 videoconferencing for medical
      education is best reserved for academic institutions that have other high
      bandwidth network requirements.

PMID- 14728769
TI  - A national survey of telehealth activity in Australian hospitals.
AB  - We conducted a national survey of Australian hospitals to assess their use of
      telehealth. Information was sought from the 814 hospitals with 10 or more beds,
      excluding the small number that provided only day surgery and seven for which we
      could not identify a contact person. A total of 564 replies were received (a 69%
      response rate). Nationally, nearly half (49%) reported that they were engaged in
      some telehealth activity. However, there was a significant difference across
      jurisdictions. Hospitals in the public sector were significantly more likely to
      report the use of telehealth than those in the private sector (62% vs 14%).
      Hospital remoteness was measured according to the Accessibility/Remoteness Index
      of Australia (ARIA). The highest levels of use were reported by hospitals in
      'very remote' and 'remote' areas (90% and 88%, respectively), with moderate
      levels of use in 'moderately accessible' and 'accessible' areas (67% and 52%,
      respectively) and the lowest level of use in 'highly accessible' areas (35%).
      This trend was significant.

PMID- 14728770
TI  - Organizational aspects of e-referrals.
AB  - Three different, well established systems for e-referral were examined. They
      ranged from a system in a single country handling a large number of cases (60,000
      per year) to a global system covering many countries which handled fewer cases
      (150 per year). Nonetheless, there appeared to be a number of common features.
      Whether the purpose is e-transfer or e-consultation, the underlying model of the
      e-referral process is: the referrer initiates an e-request; the organization
      managing the process receives it; the organization allocates it for reply; the
      responder replies to the initiator. Various things can go wrong and the
      organization managing the e-referral process needs to be able to track requests
      through the system; this requires various performance metrics. E-referral can be
      conducted using email, or as messages passed either directly between computer
      systems or via a Web-link to a server. The experience of the three systems
      studied shows that significant changes in work practice are needed to launch an e
      referral service successfully. The use of e-referral between primary and
      secondary care improves access to services and can be shown to be cost-effective.

PMID- 14728771
TI  - Telehealth responses to bio-terrorism and emerging infections.
AB  - Emerging infectious diseases, such as severe acute respiratory syndrome (SARS),
      are of huge economic importance. They are difficult to predict. The World Health
      Organization has a Global Outbreak Alert and Response Network, which was involved
      at an early stage in the SARS outbreak in 2003. Three major lessons were learned
      as a result of the SARS epidemic in 2003, involving communication, evidence-based
      action and global partnerships. It is proposed that a series of broadband global
      response networks should be developed. At a technical level the networks are
      essentially in place, such as the Internet2 global network. Suitable peripheral
      devices also exist. What has not yet been created is the appropriate software to
      allow the use of these networks, although a number of commercial products are in
      the process of development.

PMID- 14728772
TI  - Evaluation of two mobile telemedicine systems in the emergency room.
AB  - Two different prototype mobile telemedicine systems were constructed for use in
      the emergency room. They could transmit physiological signals as well as video
      pictures and sound. One device, the mobile emergency bed (MEB), was powered by
      battery and had a wireless connection to the local-area network (LAN). For the
      other, the mobile emergency server (MES), a patient monitor, video-camera and
      microphone were connected by a radio-frequency link to a server. A functional
      evaluation and a clinical evaluation (by 12 emergency doctors in six emergency
      centres) were performed on both prototypes. The bandwidth and the video quality
      of the MEB were better than those of the MES, because of the digital transmission
      of the wireless LAN. The MES was better for directing patient treatment and
      teleconsultation; the MEB was better for static patients in the emergency centre.
      In general, the MES was more suitable for practical emergency telemedicine work.

PMID- 14728774
TI  - The interpretation of biological surveys.
AB  - Biological surveys provide the raw material for assembling ecological patterns.
      These include the properties of parameters such as range, abundance, dispersion,
      evenness and diversity; the relationships between these parameters; the
      relationship between geographical distributions and landscape structure; and the
      co-occurrence of species. These patterns have often been used in the past to
      evaluate the role of ecological processes in structuring natural communities. In
      this paper, I investigate the patterns produced by simple neutral community
      models (NCMs) and compare them with the output of systematic biological surveys.
      The NCM generates qualitatively, and in some cases quantitatively, the same
      patterns as the survey data. It therefore provides a satisfactory general theory
      of diversity and distribution, although what patterns can be used to distinguish
      neutral from adaptationist interpretations of communities, or even whether such
      patterns exist, remains unclear.

PMID- 14728775
TI  - Changing partners in an obligate symbiosis: a facultative endosymbiont can
      compensate for loss of the essential endosymbiont Buchnera in an aphid.
AB  - Almost all aphids harbour an endosymbiotic bacterium, Buchnera aphidicola, in
      bacteriocytes. Buchnera synthesizes essential nutrients and supports growth and
      reproduction of the host. Over the long history of endosymbiosis, many essential
      genes have been lost from the Buchnera genome, resulting in drastic genome
      reduction and the inability to live outside the host cells. In turn, when
      deprived of Buchnera, the host aphid suffers retarded growth and sterility.
      Buchnera and the host aphid are often referred to as highly integrated almost
      inseparable mutualistic partners. However, we discovered that, even after
      complete elimination of Buchnera, infection with a facultative endosymbiotic
      gamma-proteobacterium called pea aphid secondary symbiont (PASS) enabled survival
      and reproduction of the pea aphid. In the Buchnera-free aphid, PASS infected the
      cytoplasms of bacteriocytes that normally harbour Buchnera, establishing a novel
      endosymbiotic system. These results indicate that PASS can compensate for the
      essential role of Buchnera by physiologically and cytologically taking over the
      symbiotic niche. By contrast, PASS negatively affected the growth and
      reproduction of normal host aphids by suppressing the essential symbiont
      Buchnera. These findings illuminate complex symbiont-symbiont and host-symbiont
      interactions in an endosymbiotic system, and suggest a possible evolutionary
      route to novel obligate endosymbiosis by way of facultative endosymbiotic
      associations.

PMID- 14728776
TI  - Dollo's law and the re-evolution of shell coiling.
AB  - Gastropods have lost the quintessential snail feature, the coiled shell, numerous
      times in evolution. In many cases these animals have developed a limpet
      morphology with a cap-shaped shell and a large foot. Limpets thrive in marginal
      habitats such as hydrothermal vents, the high-energy rocky intertidal areas and
      fresh water, but they are considered to be evolutionary dead-ends, unable to re
      evolve a coiled shell and therefore unable to give rise to the diversity seen
      among coiled snails. The re-evolution of a coiled shell, or any complex
      character, is considered unlikely or impossible (Dollo's law) because the loss of
      the character is followed by the loss of the genetic architecture and
      developmental mechanisms that underlie that character. Here, we quantify the
      level of coiling in calyptraeids, a family of mostly uncoiled limpets, and show
      that coiled shells have re-evolved at least once within this family. These
      results are the first demonstration, to our knowledge, of the re-evolution of
      coiling in a gastropod, and show that the developmental features underlying
      coiling have not been lost during 20-100 Myr of uncoiled evolutionary history.
      This is the first example of the re-evolution of a complex character via a change
      in developmental timing (heterochrony) rather than a change in location of gene
      expression (heterotopy).

PMID- 14728777
TI  - The impact of local heterogeneity on alternative control strategies for foot-and
      mouth disease.
AB  - The 2001 epidemic of foot-and-mouth disease (FMD) in the UK resulted in the death
      of nearly 10 million livestock at a cost that was estimated to be up to 8 billion
      pounds. Owing to the controversy surrounding the epidemic, the question of
      whether or not alternative policies would have resulted in significantly better
      control of the epidemic remains of great interest. A hexagonal lattice simulation
      of FMD in Cumbria is used to address the central question of whether or not
      better use could have been made of expert knowledge of FMD transmission to target
      pre-emptive culling, by assuming that the premises at greatest risk of becoming
      infected can be targeted for culling. The 2000 UK census and the epidemiological
      database collected during the epidemic are used to describe key characteristics
      of disease transmission, and the model is fit to the epidemic time-series. Under
      the assumptions of the model, the parameters that best fit the epidemic in
      Cumbria indicate that a policy based on expert knowledge would have exacerbated
      the epidemic compared with the policy as implemented. However, targeting more
      distant, high-risk farms could be more valuable under different epidemic
      conditions, notably, if risk factors of sufficient magnitude could be identified
      to aid in prioritizing vaccination or culling of farms at high risk of becoming
      infected.

PMID- 14728778
TI  - Contact tracing and disease control.
AB  - Contact tracing, followed by treatment or isolation, is a key control measure in
      the battle against infectious diseases. It is an extreme form of locally targeted
      control, and as such has the potential to be highly efficient when dealing with
      low numbers of cases. For this reason it is frequently used to combat sexually
      transmitted diseases and new invading pathogens. Accurate modelling of contact
      tracing requires explicit information about the disease-transmission pathways
      from each individual, and hence the network of contacts. Here, pairwise
      approximation methods and full stochastic simulations are used to investigate the
      utility of contact tracing. A simple relationship is found between the efficiency
      of contact tracing necessary for eradication and the basic reproductive ratio of
      the disease. This holds for a wide variety of realistic situations including
      heterogeneous networks containing core-groups or super-spreaders, and
      asymptomatic individuals. Clustering (transitivity) within the transmission
      network is found to destroy the relationship, requiring lower efficiency than
      predicted.

PMID- 14728779
TI  - Evolutionary dynamics of escape from biomedical intervention.
AB  - Viruses, bacteria, eukaryotic parasites, cancer cells, agricultural pests and
      other inconvenient animates have an unfortunate tendency to escape from selection
      pressures that are meant to control them. Chemotherapy, anti-viral drugs or
      antibiotics fail because their targets do not hold still, but evolve resistance.
      A major problem in developing vaccines is that microbes evolve and escape from
      immune responses. The fundamental question is the following: if a genetically
      diverse population of replicating organisms is challenged with a selection
      pressure that has the potential to eradicate it, what is the probability that
      this population will produce escape mutants? Here, we use multi-type branching
      processes to describe the accumulation of mutants in independent lineages. We
      calculate escape dynamics for arbitrary mutation networks and fitness landscapes.
      Our theory shows how to estimate the probability of success or failure of
      biomedical intervention, such as drug treatment and vaccination, against rapidly
      evolving organisms.

PMID- 14728780
TI  - Is humanity sustainable?
AB  - The principles and tenets of management require action to avoid sustained
      abnormal/pathological conditions. For the sustainability of interactive systems,
      each system should fall within its normal range of natural variation. This
      applies to individuals (as for fevers and hypertension, in medicine), populations
      (e.g. outbreaks of crop pests in agriculture), species (e.g. the rarity of
      endangerment in conservation) and ecosystems (e.g. abnormally low productivity or
      diversity in 'ecosystem-based management'). In this paper, we report tests of the
      hypothesis that the human species is ecologically normal. We reject the
      hypothesis for almost all of the cases we tested. Our species rarely falls within
      statistical confidence limits that envelop the central tendencies in variation
      among other species. For example, our population size, CO(2) production, energy
      use, biomass consumption and geographical range size differ from those of other
      species by orders of magnitude. We argue that other measures should be tested in
      a similar fashion to assess the prevalence of such differences and their
      practical implications.

PMID- 14728781
TI  - Evolution, climatic change and species boundaries: perspectives from tracing
      Lemmiscus curtatus populations through time and space.
AB  - To provide empirical evidence of species boundaries and the role of climatic
      change in affecting evolution, we documented evolution of the sagebrush vole,
      Lemmiscus curtatus, through hundreds of thousands of years by following
      populations from the middle Pleistocene to the present. We found that: (i) extant
      representatives of the species culminate a morphological transition that was
      initiated within an unusually arid and warm interglacial period, perhaps related
      to the shift from glacial-interglacial cycles dominated by a 41,000 year
      periodicity to those dominated by a 100,000 year rhythm; and (ii) sympatry of
      extant and extinct morphotypes persisted for more than 800,000 years. This
      exceptionally detailed tracing of extinct populations into extant ones suggests
      that species such as the one we studied are real entities in space, that their
      boundaries become fuzzy (although potentially diagnosable) through time and that
      unusual climatic warming may initiate significant evolutionary change manifested
      at the morphological level.

PMID- 14728782
TI  - Competition and predation in simple food webs: intermediately strong trade-offs
      maximize coexistence.
AB  - Competition and predation are fundamental interactions structuring food webs.
      However, rather than always following these neat theoretical categories, mixed
      interactions are ubiquitous in nature. Of particular importance are omnivorous
      species, such as intra-guild predators that can both compete with and predate on
      their prey. Here, we examine trade-offs between competitive and predatory
      capacities by analysing the entire continuum of food web configurations existing
      between purely predator-prey and purely competitive interactions of two consumers
      subsisting on a single resource. Our results show that the range of conditions
      allowing for coexistence of the consumers is maximized at intermediately strong
      trade-offs. Even though coexistence under weak trade-offs and under very strong
      trade-offs is also possible, it occurs under much more restrictive conditions. We
      explain these findings by an intricate interplay between energy acquisition and
      interaction strength.

PMID- 14728783
TI  - Long-term moderate elevation of corticosterone facilitates avian food-caching
      behaviour and enhances spatial memory.
AB  - It is widely assumed that chronic stress and corresponding chronic elevations of
      glucocorticoid levels have deleterious effects on animals' brain functions such
      as learning and memory. Some animals, however, appear to maintain moderately
      elevated levels of glucocorticoids over long periods of time under natural
      energetically demanding conditions, and it is not clear whether such chronic but
      moderate elevations may be adaptive. I implanted wild-caught food-caching
      mountain chickadees (Poecile gambeli), which rely at least in part on spatial
      memory to find their caches, with 90-day continuous time-release corticosterone
      pellets designed to approximately double the baseline corticosterone levels.
      Corticosterone-implanted birds cached and consumed significantly more food and
      showed more efficient cache recovery and superior spatial memory performance
      compared with placebo-implanted birds. Thus, contrary to prevailing assumptions,
      long-term moderate elevations of corticosterone appear to enhance spatial memory
      in food-caching mountain chickadees. These results suggest that moderate chronic
      elevation of corticosterone may serve as an adaptation to unpredictable
      environments by facilitating feeding and food-caching behaviour and by improving
      cache-retrieval efficiency in food-caching birds.

PMID- 14728784
TI  - Protists decrease in size linearly with temperature: ca. 2.5% degrees C(-1).
AB  - An inverse relationship between organism size and rearing temperature is widely
      observed in ectotherms ('the temperature-size rule', TSR). This has rarely been
      quantified for related taxa, and its applicability to protists also required
      testing. Here, we quantify the relationship between temperature and mean cell
      volume within the protists by a meta-analysis of published data covering marine,
      brackish water and freshwater autotrophs and heterotrophs. In each of 44
      datasets, a linear relationship between temperature and size could not be
      rejected, and a negative trend was found in 32 cases (20 gave significant
      negative regressions, p < 0.05). By combining 65 datasets, we revealed, for each
      1 degrees C increase, a cell-size reduction of 2.5% (95% CI of 1.7-3.3%) of the
      volume observed at 15 degrees C. The value did not differ across taxa (amoebae,
      ciliates, diatoms, dinoflagellates, flagellates), habitats, modes of nutrition or
      combinations of these. The data are consistent with two hypotheses that are
      capable of explaining the TSR in ectotherms generally: (i) resource, especially
      respiratory gas, limitation; and (ii) fitness gains from dividing earlier as
      population growth increases. Using the above relationship we show how changes in
      cell numbers with temperature can be estimated from changes in biomass and vice
      versa; ignoring this relationship would produce a systematic error.

PMID- 14728785
TI  - Multiple colonization of Madagascar and Socotra by colubrid snakes: evidence from
      nuclear and mitochondrial gene phylogenies.
AB  - Colubrid snakes form a speciose group of unclarified phylogeny. Their almost
      cosmopolitan distribution could be interpreted as a product of plate-tectonic
      vicariance. We used sequences of the nuclear c-mos, the mitochondrial cytochrome
      b and the 16S rRNA genes in 41 taxa to elucidate the relationships between the
      endemic colubrid genera found in Madagascar and in the Socotra archipelago. The
      well-resolved trees indicate multiple origins of both the Malagasy and the
      Socotran taxa. The Malagasy genus Mimophis was nested within the Psammophiinae,
      and the Socotran Hemerophis was closely related to Old World representatives of
      the former genus Coluber. The remaining 14 genera of Malagasy colubrids formed a
      monophyletic sister group of the Socotran Ditypophis (together forming the
      Pseudoxyrhophiinae). Molecular-clock estimates place the divergence of Malagasy
      and Socotran colubrids from their non-insular sister groups into a time-frame
      between the Eocene and Miocene. Over-seas rafting is the most likely hypothesis
      for the origin of at least the Malagasy taxa. The discovery of a large
      monophyletic clade of colubrids endemic to Madagascar indicates a need for
      taxonomic changes. The relationship of this radiation to the Socotran Ditypophis
      highlights the potential of the Indian Ocean islands to act as an evolutionary
      reservoir for lineages that have become extinct in Africa and Asia.

PMID- 14728786
TI  - Preimaginal learning determines adult response to chemical stimuli in a parasitic
      wasp.
AB  - The behavioural responses of parasitic wasps to chemical cues from their hosts
      and host plants are known to be affected by genetic and environmental components.
      In a previous study of the codling moth ectoparasitoid Hyssopus pallidus, we
      found that the response of adult parasitoids to the frass of their host
      caterpillars depended on a learning process involving plant cues. In the present
      study, we investigated how and when learning takes place. A series of experiments
      was conducted involving exposure of parasitoids to fruit cues at different
      developmental stages. While parasitoids were not able to learn the fruit cues in
      the adult stage, exposure to fruit odour at early preimaginal stages
      significantly increased the adult response to frass from fruit-fed caterpillars.
      The olfactory memory persisted through metamorphosis, with a retention time of 14
      days. Preimaginal learning was not confined to fruit cues but was also
      demonstrated for a host- and fruit-independent cue, menthol. Parasitoids exposed
      to menthol odour at the egg and larval stages no longer showed negative responses
      as adults. Sensitization to fruit cues and habituation to menthol are considered
      to be the mechanisms involved. This study provides evidence of true preimaginal
      learning of olfactory cues in a parasitic wasp.

PMID- 14728787
TI  - Pollen feeding in the butterfly Heliconius charitonia: isotopic evidence for
      essential amino acid transfer from pollen to eggs.
AB  - Heliconius and Laparus butterflies exhibit a unique pollen-collecting behaviour
      that enhances lifespan and fecundity. The specific nutritional contribution of
      pollen, however, had not been previously demonstrated. We used stable isotope
      variation to trace the carbon flow into eggs from corn pollen provided
      experimentally to ovipositing female Heliconius charitonia, and to evaluate the
      use of isotopically contrasting nectar sugars in egg amino acids. The delta(13)C
      of individual amino acids from pollen, larval host plant and the eggs from
      experimental butterflies was measured with gas chromatography/combustion/isotope
      ratio mass spectrometry (GC/C/IRMS), to evaluate amino acid transfer. The
      delta(13)C of egg essential amino acids indicated a transfer of essential amino
      acids from pollen to butterfly eggs. However, the delta(13)C of non-essential
      amino acids reflected the isotopic composition of the artificial nectar,
      indicating that H. charitonia synthesizes non-essential amino acids from dietary
      sugars. This, to our knowledge, is the first direct demonstration of amino acid
      transfer from pollen to butterfly eggs, and suggests that essential amino acids
      in particular are a key resource for extending lifespan and fecundity in
      Heliconius butterflies.

PMID- 14728789
TI  - Water: the bloodstream of the biosphere.
AB  - Water, the bloodstream of the biosphere, determines the sustainability of living
      systems. The essential role of water is expanded in a conceptual model of energy
      dissipation, based on the water balance of whole landscapes. In this model, the
      underlying role of water phase changes--and their energy-dissipative properties-
      in the function and the self-organized development of natural systems is
      explicitly recognized. The energy-dissipating processes regulate the ecological
      dynamics within the Earth's biosphere, in such a way that the development of
      natural systems is never allowed to proceed in an undirected or random way. A
      fundamental characteristic of self-organized development in natural systems is
      the increasing role of cyclic processes while loss processes are correspondingly
      reduced. This gives a coincidental increase in system efficiency, which is the
      basis of growing stability and sustainability. Growing sustainability can be seen
      as an increase of ecological efficiency, which is applicable at all levels up to
      whole landscapes. Criteria for necessary changes in society and for the design of
      the measures that are necessary to restore sustainable landscapes and waters are
      derived.

PMID- 14728790
TI  - Global analysis of river systems: from Earth system controls to Anthropocene
      syndromes.
AB  - Continental aquatic systems from rivers to the coastal zone are considered within
      two perspectives: (i) as a major link between the atmosphere, pedosphere,
      biosphere and oceans within the Earth system with its Holocene dynamics, and (ii)
      as water and aquatic biota resources progressively used and transformed by
      humans. Human pressures have now reached a state where the continental aquatic
      systems can no longer be considered as being controlled by only Earth system
      processes, thus defining a new era, the Anthropocene. Riverine changes, now
      observed at the global scale, are described through a first set of syndromes
      (flood regulation, fragmentation, sediment imbalance, neo-arheism, salinization,
      chemical contamination, acidification, eutrophication and microbial
      contamination) with their related causes and symptoms. These syndromes have
      direct influences on water uses, either positive or negative. They also modify
      some Earth system key functions such as sediment, water, nutrient and carbon
      balances, greenhouse gas emissions and aquatic biodiversity. Evolution of river
      syndromes over the past 2000 years is complex: it depends upon the stages of
      regional human development and on natural conditions, as illustrated here for the
      chemical contamination syndrome. River damming, eutrophication and generalized
      decrease of river flow due to irrigation are some of the other global features of
      river changes. Future management of river systems should also consider these long
      term impacts on the Earth system.

PMID- 14728791
TI  - Groundwater: the processes and global significance of aquifer degradation.
AB  - The exploitation of groundwater resources for human use dates from the earliest
      civilizations, but massive resource development has been largely restricted to
      the past 50 years. Although global in scope, the emphasis of this paper is on
      groundwater-based economies in a developing nation context, where accelerated
      resource development has brought major social and economic benefits over the past
      20 years. This results from groundwater's significant role in urban water supply
      and in rural livelihoods, including irrigated agriculture. However, little of the
      economic benefit of resource development has been reinvested in groundwater
      management, and concerns about aquifer degradation and resource sustainability
      began to arise. A general review, for a broad-based audience, is given of the
      mechanisms and significance of three semi-independent facets of aquifer
      degradation. These are (i) depletion of aquifer storage and its effects on
      groundwater availability, terrestrial and aquatic ecosystems; (ii) groundwater
      salinization arising from various different processes of induced hydraulic
      disturbance and soil fractionation; and (iii) vulnerability of aquifers to
      pollution from land-use and effluent discharge practices related to both urban
      development and agricultural intensification. Globally, data with which to assess
      the status of aquifer degradation are of questionable reliability, inadequate
      coverage and poor compilation. Recourse has to be made to 'type examples' and
      assumptions about the extension of similar hydrogeological settings likely to be
      experiencing similar conditions of groundwater demand and subsurface contaminant
      load. It is concluded that (i) aquifer degradation is much more than a localized
      problem because the sustainability of the resource base for much of the rapid
      socio-economic development of the second half of the twentieth century is
      threatened on quite a widespread geographical basis; and (ii) major (and long
      overdue) investments in groundwater resource and quality protection are urgently
      needed. These investments include appropriate institutional provisions, demand
      side management, supply-side enhancement and pollution control.

PMID- 14728792
TI  - Land cover change and water vapour flows: learning from Australia.
AB  - Australia is faced with large-scale dryland salinization problems, largely as a
      consequence of the clearing of native vegetation for cropland and grassland. We
      estimate the change in continental water vapour flow (evapotranspiration) of
      Australia during the past 200 years. During this period there has been a
      substantial decrease in woody vegetation and a corresponding increase in
      croplands and grasslands. The shift in land use has caused a ca. 10% decrease in
      water vapour flows from the continent. This reduction corresponds to an annual
      freshwater flow of almost 340 km(3). The society-induced alteration of freshwater
      flows is estimated at more than 15 times the volume of run-off freshwater that is
      diverted and actively managed in the Australian society. These substantial water
      vapour flow alterations were previously not addressed in water management but are
      now causing serious impacts on the Australian society and local economies. Global
      and continental freshwater assessments and policy often neglects the interplay
      between freshwater flows and landscape dynamics. Freshwater issues on both
      regional and global levels must be rethought and the interplay between
      terrestrial ecosystems and freshwater better incorporated in freshwater and
      ecosystem management.

PMID- 14728793
TI  - Dimensions and approaches for Third World city water security.
AB  - A rapid expansion of urban systems, particularly in less-developed countries,
      pose considerable challenges. Urbanization also provides opportunities for socio
      economic progress. Relative contribution from the urban sector to national
      economic growth is very high. The fate and the role of the socio-economic system
      in local, regional and national development hinges on many circumstances. Apart
      from delicate social issues, deficiencies in water provision, internal
      distribution and a hazardous water and environmental quality represent basic and
      tangible daily problems. Urban water security requires fresh thinking at two
      levels. Some kind of basin authority (corresponding to a county council, i.e. a
      formal administrative and regulatory body for the geographical area within a
      river basin) in combination with a national water policy is required, notably in
      countries that contemplate, or are in the process of implementing, regional and
      sometimes inter-basin schemes to augment supply to growing conglomerations.
      Similarly, the generation of large volumes of waste water and the associated
      threat to downstream areas cannot be effectively tackled through conventional
      urban planning. Within the urban area, and particularly in non-regulated parts,
      there is an urgent need for institutional arrangements that facilitate operations
      for providers who have the capacity and ability to function under the prevailing
      circumstances. Introduction of effective production and treatment technologies
      are other necessary and urgent prerequisites to reach urban water security in
      Third World cities.

PMID- 14728794
TI  - Water for food and nature in drought-prone tropics: vapour shift in rain-fed
      agriculture.
AB  - This paper quantifies the eco-hydrological challenge up until 2050 of producing
      food in balance with goods and services generated by water-dependent ecosystems
      in nature. Particular focus is given to the savannah zone, covering 40% of the
      land area in the world, where water scarcity constitutes a serious constraint to
      sustainable development. The analysis indicates an urgent need for a new green
      revolution, which focuses on upgrading rain-fed agriculture. Water requirements
      to produce adequate diets for humans are shown to be relatively generic
      irrespective of hydro-climate, amounting to a global average of 1,300 m(3) cap(
      1) yr(-1). Present food production requires an estimated 6,800 km(3) yr(-1) of
      consumptive green water (5,000 km(3) yr(-1) in rain-fed agriculture and 1,800
      km(3) yr(-1) from irrigated crops). Without considering water productivity gains,
      an additional 5,800 km(3) yr(-1) of water is needed to feed a growing population
      in 2,050 and eradicate malnutrition. It is shown that the bulk of this water will
      be used in rain-fed agriculture. A dynamic analysis of water productivity and
      management options indicates that large 'crop per drop' improvements can be
      achieved at the farm level. Vapour shift in favour of productive green water flow
      as crop transpiration could result in relative water savings of 500 km(3) yr(-1)
      in semi-arid rain-fed agriculture.

PMID- 14728795
TI  - The sharing of water between society and ecosystems: from conflict to catchment
      based co-management.
AB  - Human uses of freshwater resources are increasing rapidly as the world population
      rises. As this happens, less water is left to support aquatic and associated
      ecosystems. To minimize future human water shortages and undesirable
      environmental impacts, more equitable sharing of water resources between society
      and nature is required. This will require physical quantities and social values
      to be placed on both human and aquatic ecosystem requirements. Current water
      valuation systems are dominated by economic values and this paper illustrates new
      quantification and valuation methods that take more account of human well-being
      and environmental impacts. The key to the effective implementation of these more
      equitable water allocation methods is the use of catchment-based integrated water
      resources management. This holistic framework makes it possible for human and
      ecosystem water requirements and the interactions between them to be better
      understood. This knowledge provides the foundation for incorporating relevant
      social factors so that water policies and laws can be developed to make best use
      of limited water resources. Catchment-based co-management can therefore help to
      ensure more effective sharing of water between people and nature.

PMID- 14728796
TI  - Freshwater for resilience: a shift in thinking.
AB  - Humanity shapes freshwater flows and biosphere dynamics from a local to a global
      scale. Successful management of target resources in the short term tends to
      alienate the social and economic development process from its ultimate dependence
      on the life-supporting environment. Freshwater becomes transformed into a
      resource for optimal management in development, neglecting the multiple functions
      of freshwater in dynamic landscapes and its fundamental role as the bloodstream
      of the biosphere. The current tension of these differences in worldview is
      exemplified through the recent development of modern aquaculture contrasted with
      examples of catchment-based stewardship of freshwater flows in dynamic
      landscapes. In particular, the social and institutional dimension of catchment
      management is highlighted and features of social-ecological systems for
      resilience building are presented. It is concluded that this broader view of
      freshwater provides the foundation for hydrosolidarity.

PMID- 14728797
TI  - Freshwater as shared between society and ecosystems: from divided approaches to
      integrated challenges.
AB  - The paper has its focus on water's key functions behind ecosystem dynamics and
      the water-related balancing involved in a catchment-based ecosystem approach. A
      conceptual framework is being developed to address fundamental trade-offs between
      humans and ecosystems. This is done by paying attention to society's unavoidable
      landscape modifications and their unavoidable ecological effects mediated by
      water processes. Because the coevolution of societal and environmental processes
      indicates resonance rather than a cause-effect relationship, humanity will have
      to learn to live with change while securing ecosystem resilience. In view of the
      partial incompatibility of the social imperative of the millennium goals and its
      environmental sustainability goal, human activities and ecosystems have to be
      orchestrated for compatibility. To this end a catchment-based approach has to be
      taken by integrating water, land use and ecosystems. It is being suggested that
      ecosystem protection has to be thought of in two scales: site-specific biotic
      landscape components to be protected for their social value, and a catchment
      based ecosystem approach to secure sustainable supply of crucial ecosystem goods
      and services on which social and economic development depends.

PMID- 14728798
TI  - Integrated management of land and water resources based on a collective approach
      to fragmented international conventions.
AB  - Interlinked crises of land degradation, food security, ecosystem decline, water
      quality and water flow depletion stand in the way of poverty reduction and
      sustainable development. These crises are made worse by increased fluctuations in
      climatic regimes. Single-purpose international conventions address these crises
      in a piecemeal, sectoral fashion and may not meet their objectives without
      greater attention to policy, legal, and institutional reforms related to: (i)
      balancing competing uses of land and water resources within hydrologic units;
      (ii) adopting integrated approaches to management; and (iii) establishing
      effective governance institutions for adaptive management within transboundary
      basins. This paper describes this global challenge and argues that peace,
      stability and security are all at stake when integrated approaches are not used.
      The paper presents encouraging results from a decade of transboundary water
      projects supported by the Global Environment Facility in developing countries
      that test practical applications of processes for facilitating reforms related to
      land and water that are underpinned by science-based approaches. Case studies of
      using these participative processes are described that collectively assist in the
      transition to integrated management. A new imperative for incorporating
      interlinkages among food, water, and environment security at the basin level is
      identified.

PMID- 14728799
TI  - Msx homeobox gene family and craniofacial development.
AB  - Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology
      to the Drosophila muscle segment homeobox gene. These genes are expressed at
      multiple sites of tissue-tissue interactions during vertebrate embryonic
      development. Inductive interactions mediated by the Msx genes are essential for
      normal craniofacial, limb and ectodermal organ morphogenesis, and are also
      essential to survival in mice, as manifested by the phenotypic abnormalities
      shown in knockout mice and in humans. This review summarizes studies on the
      expression, regulation, and functional analysis of Msx genes that bear relevance
      to craniofacial development in humans and mice. Key words: Msx genes,
      craniofacial, tooth, cleft palate, suture, development, transcription factor,
      signaling molecule.

PMID- 14728800
TI  - Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural
      study.
AB  - Entry into mitosis is driven by signaling cascades of mitotic kinases. Our recent
      studies show that TTK, a kinetochore-associated protein kinase, interacts with
      CENP-E, a mitotic kinesin located to corona fiber of kinetochore. Using
      immunoelectron microscopy, here we show that TTK is present at the nuclear pore
      adjacent complex of interphase HeLa cells. Upon nuclear envelope fragmentation,
      TTK targets to the outermost region of the developing kinetochores of monoorient
      chromosome as well as to spindle poles. After stable attachment, throughout
      chromosome congression, TTK is a constituent of the corona fibers, extending up
      to 90 nm away from the kinetochore outer plate. Upon metaphase alignment, TTK
      departs from the kinetochore and migrates toward the centrosomes. Taken together,
      this evidence strongly supports a model in which TTK functions in spindle
      checkpoint signaling cascades at both kinetochore and centrosome.

PMID- 14728801
TI  - LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene
      transcription and DNA replication.
AB  - Enhancer II (ENII) is one of the critical cis-elements in the Hepatitis B Virus
      (HBV) genome for the hepatic viral gene transcription and DNA replication. The
      liver-specific activity of ENII is regulated by multiple liver-enriched
      transcription factors, including LRH-1/hB1F, HNF1, HNF3b, HNF4 and C/EBP.
      Knowledge on the interplay of these important factors is still limited. In this
      study, we demonstrate a functional synergism between the orphan nuclear receptor
      LRH-1/hB1F and the homeoprotein HNF1 in up-regulating the liver-specific activity
      of ENII. This synergism is sufficient for initiating the viral gene transcription
      and DNA replication in non-hepatic cells. We have defined the activation domains
      in hB1F and HNF1 that contribute to the synergism. We further show that hB1F and
      HNF1 can interact directly in vitro and have mapped the domains required for this
      interaction.

PMID- 14728802
TI  - Distinct expression profiles of transcriptional coactivators for thyroid hormone
      receptors during Xenopus laevis metamorphosis.
AB  - The biological effects of thyroid hormone (T3) are mediated by the thyroid
      hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic
      processes that are dependent on T3. T3 regulates a series of orchestrated
      developmental changes, which ultimately result in the conversion of an aquatic
      herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to
      TRs, which in turn recruit coactivators, leading to gene activation. The best
      studied coactivators belong to the p160 or SRC family. Members of this family
      include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1.
      These SRCs interact directly with liganded TR and function as adapter molecules
      to recruit other coactivators such as p300/CBP. Here, we studied the expression
      patterns of these coactivators during various stages of development. Amongst the
      coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically
      upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are
      expressed throughout postembryonic development with little change in their
      expression levels. These results support the view that these coactivators
      participate in gene regulation by TR during metamorphosis.

PMID- 14728803
TI  - Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the
      spleen and thymus.
AB  - Hindlimb unloading (HU) in rodent is a well-accepted ground-based model used to
      simulate some of the conditions of space flight and reproduce its deleterious
      effects on the musculoskeletal, cardiovascular and immune systems. In this study,
      the effects of HU on lymphocyte homeostasis in the spleen and thymus of mice were
      examined. HU was found to drastically deplete various cell populations in the
      spleen and thymus. These changes are likely to be mediated by apoptosis, since
      DNA strand breaks indicative of apoptosis were detected by terminal
      deoxynucleotidyl transferase-mediated nick end-labeling in both splenocytes and
      thymocytes. Surprisingly, administration of opioid antagonists or interference
      with the Fas-FasL interaction was able to block HU-induced reductions of
      splenocytes, but not thymocytes. On the other hand, steroid receptor antagonists
      blocked the reduction of lymphocyte numbers in both spleen and thymus. Therefore,
      the effects of HU on the homeostasis of splenocytes and thymocytes must be
      exerted through distinct mechanisms.

PMID- 14728804
TI  - Phage display selection on whole cells yields a small peptide specific for HCV
      receptor human CD81.
AB  - The human CD81 (hCD81), the most recently proposed receptor of hepatitis C virus
      (HCV), can especifically bind to HCV envelope glycoprotein 2 (E2). In this study,
      hCD81-expressing murine NIH/3T3 cells were used to select hCD81-binding peptides
      from a phage displayed nonapeptide library (PVIII9aaCys). Eighteen of the 75
      clones selected from the library showed specific binding to the hCD81-expressing
      NIH/3T3 cells by enzyme linked immunosorbent assay (ELISA) and competitive
      inhibition test. Twelve out of the 18 clones shared the amino acid motif
      SPQYWTGPA. Sequence comparison of the motif showed no amino acid homology with
      the native HCV E2. The motif-containing phages could competitively inhibit the
      ability of HCV E2 binding to native hCD81-expressing MOLT-4 cells, and induce HCV
      E2 specific immune response in vivo. These results suggest that the selected
      motif SPQYWTGPA should be a mimotope of HCV E2 to bind to hCD81 molecules. Our
      findings cast new light on developing HCV receptor antagonists.

PMID- 14728805
TI  - An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral
      efficacy.
AB  - ONYX-015 is an attractive therapeutic adenovirus for cancer because it can
      selectively replicate in tumor cells and kill them. To date, clinical trials of
      this adenovirus have demonstrated marked safety but not potent enough when it was
      used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy
      strategy and in this way, we constructed an armed therapeutic oncolytic
      adenovirus system, ZD55-gene, which is not only deleted of E1B 55-kD gene similar
      to ONYX-015, but also armed with foreign antitumor gene. ZD55-gene exhibited
      similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro.
      Importantly, the carried gene is expressed and the expression level can increase
      with the replication of virus. Consequently, a significant antitumoral efficacy
      was observed when ZD55-CD/5-FU was used as an example in nude mice with
      subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-gene,
      which utilizing the Gene-ViroTherapy strategy, is more efficacious than each
      individual component in vivo.

PMID- 14728806
TI  - Karyotype differentiation and reproductive isolation among natural populations of
      Drosophila lacertosa.
AB  - Drosophila lacertosa is widely distributed from northern India to Far East of
      Russia throughout China. We have studied geographical distributions of three
      kinds of chromosomal karyotypes, type D (2n=10, 4 pairs of V-shaped metacentric
      chromosomes and a pair of micro-chromosomes), type L (2n=10, 5V with a pair of
      large-sized heterochromatic autosomes) and type M (2n=10, 5V with middle-sized
      ones). Type D was found exclusively in local populations of D. lacertosa
      distributed in Yun-Gui Plateau, southwestern China. Both type L and M have a wide
      range of distribution, and the former occurred in subtropical regions of China
      including Taiwan Island, whereas the latter in cool temperate regions of East
      Asia covering Far East of Russia, Korea and the Japan Islands. A strong pre
      mating isolation was detected between flies with type D and those with type L or
      M. These data demonstrate that genetic differentiation leading to cryptic
      speciation might have occurred in natural populations of Drosophila lacertosa.

PMID- 14728807
TI  - Identification of two distinct transactivation domains in the pluripotency
      sustaining factor nanog.
AB  - Nanog is a newly identified homeodomain gene that functions to sustain the
      pluripotency of embryonic stem cells. However, the molecular mechanism through
      which nanog regulates stem cell pluripotency remains unknown. Mouse nanog encodes
      a polypeptide of 305 residues with a divergent homeodomain similar to those in
      the NK-2 family. The rest of nanog contains no apparent homology to any known
      proteins characterized so far. It is hypothesized that nanog encodes a
      transcription factor that regulates stem cell pluripotency by switching on or off
      target genes. To test this hypothesis, we constructed fusion proteins between
      nanog and DNA binding domains of the yeast transcription factor Gal4 and tested
      the transactivation potentials of these constructs. Our data demonstrate that
      both regions N- and C- terminal to the homeodomain have transcription activities.
      Despite the fact that it contains no apparent transactivation motifs, the C
      terminal domain is about 7 times as active as the N-terminal one. This unique
      arrangement of dual transactivators may confer nanog the flexibility and
      specificity to regulate downstream genes critical for both pluripotency and
      differentiation of stem cells.

PMID- 14728809
TI  - Gene expression profile favoring phenotypic reversion: a clue for mechanism of
      tumor suppression by NF-IL6 3'UTR.
AB  - Transfection of cDNA in 3'untranslated region of human nuclear factor for
      interleukin-6 (NF-IL6 3'UTR) induced tumor suppression in a human hepatoma cell
      line. cDNA array analysis was used to reveal changes in gene expression profile
      leading to tumor suppression The results indicate that this suppression was not
      due to activation of dsRNA-dependent protein kinase, nor to inactivation of
      oncogenes; rather, all the changes in expression of known genes, induced by NF
      IL6 3'UTR cDNA may be ascribed to the suppression of cellular malignancy.
      Therefore, our results imply that this 3'untranslated region may have played role
      of a regulator of gene expression profile.

PMID- 14728808
TI  - Mortalin imaging in normal and cancer cells with quantum dot immuno-conjugates.
AB  - Quantum dots are the nanoparticles that are recently emerging as an alternative
      to organic fluorescence probes in cell biology and biomedicine, and have several
      predictive advantages. These include their i) broad absorption spectra allowing
      visualization with single light source, ii) exceptional photo-stability allowing
      long term studies and iii) narrow and symmetrical emission spectrum that is
      controlled by their size and material composition. These unique properties allow
      simultaneous excitation of different size of quantum dots with a single
      excitation light source, their simultaneous resolution and visualization as
      different colors. At present there are only a few studies that have tested
      quantum dots in cellular imaging. We describe here the use of quantum dots in
      mortalin imaging of normal and cancer cells. Mortalin staining pattern with
      quantum dots in both normal and cancer cells mimicked those obtained with organic
      florescence probes and were considerably stable.

PMID- 14728810
TI  - The effects of GM1 and bFGF synergistically inducing adult rat bone marrow
      stromal cells to form neural progenitor cells and their differentiation.
AB  - OBJECTIVE: To investigate the effects of GM1 on inducing adult rat bone marrow
      stromal cells (MSCs) to form neural progenitor cells and their differentiation.
      METHODS: Purified MSCs were induced by different components of basic fibroblast
      growth factor (bFGF) alone, GM1 alone or combination of bFGF with GM1. After 3
      days' incubation, fibronectin and collagen I were detected with
      immunocytochemistry, and nestin was detected with immunofluorescence. Neuron
      specific enolase (NSE), glial fibrillary acidic protein (GFAP) and galactose
      cerebroside (GalC) were detected with immunocytochemistry after 7 days'
      incubation. RESULTS: After induction with bFGF alone or combination of bFGF and
      GM1, some MSCs exhibited the phenotypes of neural progenitor cells, and then
      neurons and astrocytes. In these two groups, the positive cells for fibronectin
      and collagen I decreased markedly after 3 days' induction. At the same time, the
      positive cells for nestin increased markedly. After 7 days' induction, NSE and
      GFAP-positive cells increased significantly. Furthermore, the addition of bFGF
      and GM1 caused the maximal variation. However, addition of GM1 alone had no
      inductive effects. CONCLUSIONS: Combination of bFGF with GM1 may synergistically
      promote the transformation of MSCs and differentiation into neurons and astrocyte
      like cells. The results suggest a promising route for the application of MSCs.

PMID- 14728811
TI  - Treatment of ipsilateral hip and femoral shaft fractures with reconstructive
      intramedullary interlocking nail.
AB  - OBJECTIVE: To evaluate the results of reconstructive intramedullary interlocking
      nail in the treatment of ipsilateral hip and femoral shaft fractures. METHODS:
      From August 1997 to November 2001, 13 patients were treated with the
      reconstructive intramedullary interlocking nail. Nine patients were associated
      with ipsilateral femoral neck fractures, three with ipsilateral intertrochanteric
      fractures, and one with subtrochanteric fracture. RESULTS: The follow-up time was
      from 6 to 38 months with an average of 14 months. All the femoral shaft and hip
      fractures healed up well. There was no nonunion of the femoral neck, and only one
      varus malunion. No patient had avascular necrosis of the femoral head. The
      average healing time for femoral neck fracture was 4.6 months and for shaft
      fracture 5.8 months. The joint movement and other functions were fairly resumed.
      CONCLUSIONS: The reconstructive intramedullary interlocking nail, with less
      trauma, reliable fixation, and high rate of fracture healing, is an ideal method
      of choice in the treatment of ipsilateral hip and femoral shaft fractures.

PMID- 14728812
TI  - Construction of the subtractive cDNA library of injured adult and fetal rabbit
      skins.
AB  - OBJECTIVE: Early gestational mammalian fetuses possess the amazing ability to
      heal cutaneous wounds in a scarless fashion. Over the past years, scientists have
      been working to decipher the mechanisms underlying this regenerative repair. The
      remarkable phenotypic differences between fetal and adult healings behooves us to
      learn their characteristics in genetics, which represents potentially important
      mechanisms involved in wound repair observed in fetal versus adult tissues. In
      this sense, it is reasonable to construct subtractive cDNA library for future
      research. METHODS: Middle laparotomy and hysterotomy were performed on pregnant
      rabbits at 20-day gestation to expose the fetal back, and a longitudinal incision
      through the skin was made on the back of the fetus. The traumatized fetal skin
      was harvested 12 hours post-operation, the fetus control and traumatized adult
      skin specimens were taken at the same time. dscDNA was synthesized from total RNA
      of skin samples with SMART technology. Taking one of the three samples as Tester
      respectively and the other two as Drivers, we obtained 1 forward and 2 reverse
      hybridization products. After being amplified with selective polymerase chain
      reaction, the products were inserted into a vector, and then transferred into E.
      coli HB101. The colonies were screened afterwards. RESULTS: The wounded fetuses
      were alive for a long time even after birth. Every determinant step, such as RNA
      isolation, cDNA synthesis, Rsa I digestion, adaptor ligation and hybridization,
      was well-operated. Subtractive efficiency identification demonstrated that the
      suppression subtractive hybridization (SSH) was successful. Insertion into vector
      and transferring to E. coli were satisfactory. CONCLUSIONS: Instead of classic
      SSH, an improved SSH with 2 Drivers was applied for the experiment. Results
      confirmed that the improved program was reasonable and correct in both theory and
      practice. The subtractive cDNA library we have obtained is going to be used for
      future researches to reveal scarless healing related gene(s) and its (their)
      expression.

PMID- 14728813
TI  - Effect of nano-hydroxyapatite/collagen composite and bone morphogenetic protein-2
      on lumbar intertransverse fusion in rabbits.
AB  - OBJECTIVE: To investigate the effect of nano-hydroxyapatite/collagen
      (nHA/collagen) composite as a graft extender and enhancer when combined with
      recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar
      intertransverse fusion in rabbits. METHODS: Sixty-four adult female New Zealand
      white rabbits, aged 1 year and weighing 3.5-4.5 kg, underwent similar
      posterolateral intertransverse process arthrodesis and were randomly divided into
      4 groups based on different grafts: autogenous cancellous bone alone (ACB group),
      nHA/collagen alone (HAC group), half autogenous cancellous bone and half
      nHA/collagen (ACB+HAC group) and nHA/collagen combined with rhBMP-2 (HAC+BMP
      group). The fusion masses were analyzed by manual palpation, radiography,
      biomechanical testing and histological examination. RESULTS: Fusion was observed
      in 4 cases in the 6th week and in 5 cases in the 10th week after surgery in ACB
      group. No case showed fusion in HAC group. In ACB+HAC group, there was fusion in
      3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC+BMP
      group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and
      in 6 cases in the 10th week after surgery. It suggested that ACB, ACB+HAC and
      HAC+BMP groups showed similar fusion ratio and mechanical strength in the 6th and
      10th week after surgery. According to the microstructure analysis of the samples,
      nHA/collagen had no negative effect when implanted together with ilium autograft.
      In HAC+BMP group, new bone-like tissue was observed in the 2nd week
      postoperatively, and nearly all of the implanted composites were replaced by
      mature bone matrix and new bones in 10th week postoperatively. CONCLUSIONS: The
      nHA/collagen, especially combined with rhBMP-2, is a promising bone substitute,
      for it has quick biodegradation, fine bone-bending ability, and high
      osteoconductivity on posterolateral spinal fusion in rabbits.

PMID- 14728814
TI  - Pretreatment effect of adenosine on activation of NF-kappaB and level of TNF
      alpha during myocardial ischemia and reperfusion in rats.
AB  - OBJECTIVE: To study the pretreatment effect of adenosine on NF-kappaB nuclear
      activity in ischemia/reperfusion myocardium in rats. METHODS: Eighteen healthy
      male S-D rats were randomly divided into three groups. Group I was the control
      group. The other two groups were subjected to 30 minutes of ischemia, followed by
      2 hours of reperfusion. In group III, adenosine was given 40 microg.kg(-1).min(
      1) 30 minutes before coronary artery occlusion. The NF-kappaB in nuclear was
      extracted and measured with western blot analysis. TNF-alpha levels in myocardium
      were measured with enzyme-linked immunosorbent assay (ELISA) system. All the data
      were recorded with mean +/- SEM, differences at the 95% confidence level were
      considered significant. RESULTS: NF-kappaB activity in the nucleus significantly
      increased after ischemia/reperfusion and TNF-alpha levels changed. Adenosine
      significantly inhibited NF-kappaB activity in nucleus, and concomitantly
      decreased the level of TNF-alpha in myocardium. CONCLUSIONS: Adenosine modulation
      of NF-kappaB activation may be the cellular molecular mechanism of decreasing of
      TNF-alpha. The cardioprotective action of adenosine may be involved in the
      differential modulation of NF-kappaB activation during myocardial
      ischemia/reperfusion.

PMID- 14728815
TI  - Treatment of 209 cases of liver injury.
AB  - OBJECTIVE: To summarize the experience of the treatment of traumatic
      hepatorrhexis. METHODS: The clinical data of 209 cases of liver trauma treated in
      the three affiliated hospitals of the Third Military Medical University from 1989
      to 1999 were retrospectively analyzed. Among the 209 patients, 108 (51.7%) had
      Grade III or more severe liver injury. Operative treatment was performed in 186
      cases and preservative treatment in 23. RESULTS: In the operated group, 169
      patients were cured. The complications occurred in 18 patients and 17 of them
      died. In the non-operated group, the complications occurred in 22 patients and
      only 1 of them died. CONCLUSIONS: Severe injury and delayed treatment are two
      major factors leading to death from liver injuries. Surgical intervention is
      still the principal measure to treat traumatic hepatorrhexis. The indications for
      non-operative treatment should be carefully selected.

PMID- 14728816
TI  - Changes of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 in
      brain and plasma after brain injury in rats.
AB  - OBJECTIVE: To study the changes of interleukin-1 beta (IL-1beta), tumor necrosis
      factor alpha (TNFalpha) and interleukin-6 (IL-6) levels in brain and plasma after
      brain injury and to assess the relationship between the cytokine levels and
      injury severity in rats. METHODS: A total of 51 male Wistar rats, weighing 280
      340 g, were anesthetized with chloral hydrate (400 mg/kg body weight) through
      intraperitoneal injection and fixed on a stereotaxic instrument. Severe brain
      injury was created in 16 rats (severe injury group) and moderate brain injury in
      18 rats (moderate injury group) by a fluid percussion model, and cytokine levels
      of IL-1beta, TNFalpha and IL-6 were measured with biological assay. And sham
      operation was made on the other 17 rats (control group). RESULTS: In the control
      group, the levels of IL-1beta, TNFalpha and IL-6 were hardly detected in the
      cortex of the rats, but in the ipsilateral cortex of the rats in both injury
      groups, they increased obviously at 8 hours after injury. The increasing degree
      of these cytokines had no significant difference between the two injury groups.
      The levels of IL-6 in the plasma of all the rats increased slightly, whereas the
      levels of IL-1beta and TNFalpha were undetectable. CONCLUSIONS: The increase of
      IL-1beta, TNFalpha and IL-6 levels is closely related to brain injury. The
      increased cytokine levels in the central nervous system are not parallel to those
      in the peripheral blood. It suggests that inflammatory cytokines play important
      roles in the secondary neural damage after brain injury.

PMID- 14728817
TI  - Pancreatic enzymes in the gut contributing to lung injury after
      trauma/hemorrhagic shock.
AB  - OBJECTIVE: To examine whether pancreatic proteolytic enzymes involve in lung
      injury induced by trauma/hemorrhagic shock (T/HS). METHODS: Male Sprague-Dawley
      rats received intraluminal or intravenous pancreatic serine protease inhibitor, 6
      amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate (ANGD) during laparotomy
      (trauma), and were subjected to 90 minutes of T/HS or trauma-sham shock (T/SS).
      Degree of lung injury was assessed 3 hours after resuscitation with Ringer's
      lactate solution. RESULTS: Lung permeability, pulmonary myeloperoxidase levels
      and the ratio of bronchoalveolar lavage fluid protein to plasma protein increased
      after T/HS, and significantly decreased in intraluminal-ANGD treated but not in
      intravenous-ANGD treated rats. Histological analysis demonstrated fewer injured
      villi in the intraluminal-ANGD treated rats compared with those in the control
      rats. Linear regression analysis revealed that the percentage of injured ileal
      mucosal villi directly related to pulmonary polymorphic neutrophil sequestration
      and lung permeability to Evans blue dye. CONCLUSIONS: Pancreatic proteolytic
      enzymes in the ischemic gut may be important toxic factors contributing to lung
      injury after T/HS.

PMID- 14728818
TI  - Effect of basic fibroblast growth factor and hyaluronic acid on proliferation of
      rabbit chondrocytes in vitro.
AB  - OBJECTIVE: To investigate the effect of basic fibroblast growth factor (bFGF) and
      hyaluronic acid (HA) on the proliferation of rabbit chondrocytes in vitro.
      METHODS: Chondrocytes from the knee joints of New Zealand white rabbits were
      cultured. bFGF or HA or both were added into the culture medium respectively, and
      the proliferation of the chondrocytes was measured with MTT 3-(4, 5
      dimethylthiazol-2-yl) 2, 5-diphenyl-tetra-zolium bromide. (MTT, Sigma, M2128).
      RESULTS: Basic fibroblast growth factor (10 ng/ml) with low concentration of
      fetal bovine serum in the culture medium promoted the proliferation of
      chondrocytes significantly, and this effect reached its maximum when
      concentration of bFGF reached 50 ng/ml. HA itself had no effect on the
      proliferation of chondrocytes. However, when bFGF was used in combination with
      HA, especially when the concentration of bFGF was 50-500 ng/ml and that of HA was
      10-50 ng/ml, the effect on the proliferation of chondrocytes was much more than
      when bFGF or HA was used alone. CONCLUSIONS: bFGF can promote the proliferation
      of chondrocytes. HA, which has no effect on the proliferation of the cells, can
      maintain a normal growth of chondrocytes. When bFGF is used in combination with
      HA, more proliferation is obtained.

PMID- 14728819
TI  - Application of radionuclide imaging to hepatic impact injury in rabbits.
AB  - OBJECTIVE: To investigate the role and clinical value of radionuclide imaging in
      hepatic impact injuries in rabbits. METHODS: Rabbits were experimentally impacted
      on the liver with BIM-IV bio-impact machine. Liver imaging was performed with
      99mTc labeled sodium phytate. Liver blood pool imaging was performed with 99mTc
      stannous pyrophosphate labeled red blood cells. The results of radionuclide
      imaging were compared with the anatomic results. RESULTS: There was significant
      difference between the images of the injured liver and the control. Radio
      diminution and defect were shown in the injured liver areas. Various sorts of
      abnormal radioactivity distribution were observed with hepatic blood pool
      imaging. The results of the liver imaging and liver blood pool imaging were
      accorded with the results of the anatomic findings. CONCLUSIONS: Radionuclide
      imaging may well display the changes of hepatocellular structures and functions
      after injury, which is valuable in locating the concrete injured position and
      differentiating the injured degrees of liver.

PMID- 14728820
TI  - Treatment of very severe brain injuries.
AB  - OBJECTIVE: To sum up the experience in treating very severe traumatic brain
      injuries. METHODS: Retrospective analysis of 68 patients with very severe
      traumatic brain injuries treated in our hospital from 1997 to 2002 was done.
      RESULTS: Forty-one (60%) patients died. In the 50 patients treated surgically 27
      (40%) survived, 8 recovered well, 9 had moderate disability and 10 had severe
      deficits. The 18 patients treated non-operatively all died. CONCLUSIONS: Much
      attention should be given to the observation of the changes of severe brain
      injuries with cranial base injury. Timely operative decompression, basic life
      support, keeping effective brain blood perfusion and effective oxygen supply,
      improving cerebral microcirculation and preventing or controlling complications
      are the main methods to raise the successful rate of treating very severe brain
      injuries and the life quality of the patients.

PMID- 14728821
TI  - Clinical manifestations and significance of post-traumatic thoracolumbar
      syringomyelia.
AB  - OBJECTIVE: To analyze the pathogenic mechanism and the clinical significance of
      post-traumatic thoracolumbar syringomyelia through reviewing the clinical
      manifestations. METHODS: The data of 15 patients (14 males and 1 female, aged
      from 28 to 56 years, with an average of 36 years) with post-traumatic
      syringomyelia treated in our hospital from December 1997 to February 2002 were
      studied retrospectively. Two patients suffered from T11 fractures, 7 from T12
      fractures and 6 from L1 fractures. There were 12 patients with burst fractures
      and 3 with fracture dislocations. Anterior decompression, bone graft, bone fusion
      and internal fixation were made on 6 patients, posterior decompression, bone
      graft, bone fusion and internal fixation on 1 patient, and non-surgical treatment
      on 8 patients. RESULTS: Syringomyelia of the patients was diagnosed accurately
      with magnetic resonance imaging at 0.5-4 years after the original thoracolumbar
      fracture. The cavern was round in 6 cases, elliptic in 6 cases, and irregular in
      3 cases. The patients also suffered from pain (80%), myodynamia attenuation in
      lower extremities (66.7%), aggravated spasm (46.7%), sensation loss or
      hypesthesia (46.7%), decreased coordinate function of lower extremities (20%) and
      autonomic nerve symptom (6.7%). CONCLUSIONS: Post-traumatic thoracolumbar
      syringomyelia should be suspected if the patient has new neurological symptoms,
      such as myodynamia attenuation in lower extremities, after the neural function
      becomes stable for certain time.

PMID- 14728822
TI  - Olmesartan inhibits the expression of monocyte chemoattractant protein-1 and
      tumor necrosis factor-alpha and improves vascular remodeling after vascular
      injury in mouse.
AB  - OBJECTIVE: To investigate the neointima formation and the expression of monocyte
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in
      cuff-induced vascular injury in mouse model, and to examine the effect of
      angiotensin II type 1 receptor (AT1) blocker, olmesartan, on MCP-1 and TNF-alpha
      expression and consequently vascular remodeling. METHODS: Vascular injury was
      induced by polyethylene cuff-placement around the mouse femoral artery. Some mice
      were treated with AT1 receptor blocker, olmesartan, at the dose of 3 mg.kg(
      1).day(-1) with an osmotic minipump. Neointima formation and the proliferation of
      vascular smooth muscle cells (VSMCs) were measured by morphometric analysis and
      bromodeoxyuridine (BrdU) incorporation. MCP-1 and TNF-alpha expression was
      detected by Western blot and immunohistochemical staining. RESULTS: We observed
      neointima formation 14 days after cuff placement as well as VSMCs proliferation
      in the media and neointima. Cuff placement also induced MCP-1 and TNF-alpha
      expression in the media and neointima that the VSMCs specifically existed.
      Treatment of mice with olmesartan at a dose of 3 mg.kg(-1).day(-1), which did not
      influence systolic blood pressure, significantly decreased neointima formation
      and the proliferation of VSMCs. Olmesartan also inhibited MCP-1 and TNF-alpha
      expression in the injured arteries. CONCLUSIONS: Our results demonstrate that
      blockade of AT1 receptor inhibits MCP-1 and TNF-alpha expression and thereby
      improves vascular remodeling.

PMID- 14728823
TI  - Splenosis simulating an intrahepatic mass.

PMID- 14728824
TI  - [The relationship between the peripheral blood of CD61, CD63, PAC-1 and the
      transplant kidney function].
AB  - OBJECTIVES: To explore the relationships between the peripheral blood levels of
      CD61, CD63, PAC-1 and the incidence of acute rejection and tubular necrosis after
      renal transplantation, and recovery of the graft function. METHODS: The
      peripheral blood levels of CD61, CD63, and PAC-1 of 86 patients with uremia in
      different stages before and after transplantations were analyzed by flow
      cytometry. The patients were divided into three groups: (1) twenty-nine patients
      with normal grafts function, (2) hirty with acute rejection and (3) twenty-seven
      with acute tubular necrosis. The patients with acute rejection were randomly
      divided into treatment group with anticoagulants and cntrol group. RESULTS: The
      peripheral blood levels of CD61, CD63 and PAC-1 significantly increased (P <
      0.05) in the patients with acute rejection, in comparison with those with normal
      grafts function and those with acute tubular necrosis. The peripheral blood
      levels of CD61, CD63 and PAC-1 in patients with acute rejection in anticoagulants
      therapy was lower, recovery time of the grafts function was shorter, one-year
      survival rates of patients and grafts were higher, as compared with those of
      controls. CONCLUSIONS: The patients with acute rejection have significantly high
      peripheral blood levels of CD61, CD63 and PAC-1 before transplantation, however,
      these values in patients with acute tubular necrosis are not high, this
      suggesting that acute rejection might relate to platelet activation, while acute
      tubular necrosis might not relate to it. After anticoagulants therapy in patients
      with acute rejection, the grafts function might recover faster and their one-year
      survival rates and grafts might be higher in those with CD61, CD63 and PAC-1
      decreasing remarkably.

PMID- 14728825
TI  - [Over 55 years-old live-related donor kidney transplants: a report of 12 cases].
AB  - OBJECTIVE: To evaluate the risk factors of the over 55-year-old donor and the
      safety and efficacy of the donor, and the recipient with the immediate and long
      term of the kidney. METHODS: The living-related donor kidney transplantation in
      15 cases was performed in our unit from October 1999 to April 2002. Of these, 12
      donors were over 55 with age ranging from 55 to 73 years-old and mean age of 62,
      75 years. 5 donors were male and 7 were female. Father in 5 cases and 6 and 1
      were mother and grandmother, respectively. The donors were evaluated depending on
      general state of health, hypertension, diabate and important organa in condition;
      and renal function by creatinine (Cre), creatinine clearance (Ccr), Glomerular
      filtration rate (GFR), B ultrasound and renal arteriograph prior to operation.
      The all receipients with ages ranging from 14 to 46 years with end-stage renal
      diseases (ESRD) from and their mean age was 32.9 years. The donor' left
      nephrectomy was performed in 10 cases and right nephrectomy in 2. Warm-ischemia
      time was from 70 s to 170 s (mean time, 92 s). Cold-ischemia time was from 60
      minutes to 120 minutes and mean 84 minutes. The follow-up is from 12 to 42 months
      and mean 20, 84 months. RESULTS: All the 12 donors were perfectly recovered
      during operation and postoperation. During their 11-day stay in the hospital no
      complications was observed. The donor' creatinine was raised to about 12 to 34
      micro mol/L (mean, 22 micro mol/L). One recipient died from lung infection at 28
      days postoperative and 1 died due to liver failure with normal graft function
      after transplanted 6 months and yet one recipient with delayed graft function had
      recovered by 12 times dialysis. The remain recipient had a better recovered.
      CONCLUSION: Aged (>or= 55 years-old) donor renal transplantation can be carried
      out as the poor supply of can be used kidney but must to controled the indication
      and the prepare to be accomplished seriously.

PMID- 14728826
TI  - [Diagnosis and therapy of the nutcracker phenomenon: long-term follow-up].
AB  - OBJECTIVE: To study the diagnosis of adult nutcracker phenomenon (NCP) and assess
      the therapeutic value of endovascular stenting (ES) and superior mesentery artery
      transposition (SMAT) for the treatment of NCP in long-term follow-up. METHODS:
      Six patients (6 men) aged 16 and 34 years old (mean age, 22.7 +/- 18.0 years)
      were diagnosed as having NCP using the examination of the doppler ultrasound
      and/or magnetic resonance of artery/digital radiography (MRA/DSA). Three patients
      underwent ES and 3 patients received SMAT for the treatment of the NCP patients
      associated with recurrent gross hematuria and left flank pain. Doppler ultrasound
      and urine examination were used at pre- and post-operation. RESULTS: In 3
      patients who underwent SMAT, the postoperative complications comprised
      retroperitoneal hematoma necessitating surgical revision (n = 1). Functional
      disorder of intestine (n = 1) and paralytic ileus (n = 1) that were resolved by
      conservative management. In 3 patients who experienced ES, 1 patient received
      surgical revision because the position of stent was not suitable in left renal
      vein but no other complication took place. During the follow-up of 6
      approximately 50 months (mean 24.7 +/- 18.0 months), except that 1 patient's
      hematuria disappears at rest and reappears after motion while the other 5
      patients remain asymptomatic and free of hematuria. The dopplar ultrasound showed
      the left renal vein diameters of the angel segment between superior mesentery
      artery and aorta were (0.18 +/- 0.05) cm preoperation and (0.65 +/- 0.17) cm
      postoperation, P < 0.001; the left renal vein diameters of the portal segment
      were (0.89 +/- 0.22) cm preoperation and (0.79 +/- 0.20) cm postoperation, P =
      0.003; the left renal vein diameter's ratio between portal and angel segment were
      (4.99 +/- 0.79) preoperation and (1.23 +/- 0.16) postoperation, P < 0.001.
      CONCLUSIONS: Dopplar ultrasound plays a very important role in the diagnosis of
      adult NCP. SMAT is an efficient surgical approach to the treatment of the
      nutcracker phenomenon and is associated with an acceptable risk of complications.
      But ES is safer and more efficient than SMAT and may represent a valuable
      approach to lessening the morbidity of surgical procedures. ES is a new
      therapeutic method for adult NCP.

PMID- 14728827
TI  - [The role of cell adhesion, multidrug resistance and cell proliferation in short
      term recurrent cases with T1G3 superficial bladder cancer].
AB  - OBJECTIVE: To evaluate the roles of cell adhesion, multidrug resistance and cell
      proliferation in short-term recurrent cases with superficial bladder cancer, and
      the prognostic value of the three indexes. METHODS: Immunohistochemical staining
      for E-cad, P-gp and Ki-67 was performed on the tumors of 100 patients with stage
      T0-T1 transitional cell carcinoma of the bladder who had been included in a
      retrospective research by follow-up. RESULTS: E-cad and P-gp expression was
      positive in 51 (43.2%)and 17 (14.4%) of the tumors, respectively and mean
      proliferation index (PI) was 22.1%. The decrease in E-cad expression was
      accompanied with the increasing recurrent episodes (P < 0.05), while increase of
      P-gp expression and PI were accompanied with the increasing recurrence episodes
      (P < 0.05). There was significant difference according to E-cad, P-gp positivity
      and between T(1)G(3) patients and no-T(1)G(3) patients (P < 0.05). There was
      negative correlation of E-cad expression with P-gp expression and PI.
      CONCLUSIONS: Minimum adhesion, strong drug resistance and maximum proliferation
      are the main factors that promote short-term recurrence of superficial bladder
      cancer and also the inherent reasons for easy recurrence and high malignancy of
      T(1)G(3) tumors. During this course, the three aspects may interact.

PMID- 14728828
TI  - [An experimental study on high intensity focused ultrasound combined with
      mitomycin treatment of bladder tumor].
AB  - OBJECTIVE: To study the therapeutic effect and synergistic inhibition effect of
      high intensity focused ultrasound in combination with mitomycin on T739 mice
      bladder tumor. METHODS: BTT739 tumor-bearing mice receiving HIFU and/or mitomycin
      in two weeks, were divided into control group, low dose chemotherapy group, high
      dose chemotherapy group, HIFU group and HIFU combined chemotherapy group. The
      growth of mice tumor volume was observed in two weeks, by which we counted tumor
      volume doubling time and performed the growth curve. All specimens were analysed
      histologically. RESULTS: HIFU combined mitomycin has significant synergistic
      inhibition effect. Tumor tissue damage such as huge coagulation necrosis was
      observed using light microscopy. However, there were still some remaining alive
      cells. The apoptosis of tumor cell in HIFU group and HIFU combined chemotherapy
      group obviously increased in comparison with other groups. CONCLUSIONS: HIFU
      group, HIFU combined chemotherapy group can distinctively inhibit tumor growth;
      HIFU combined with mitomycin has notable synergistic inhibitory effect. HIFU may
      induce the apoptosis of tumor cell.

PMID- 14728829
TI  - [The relationship between phenotype transformation and biomechanical properties
      of detrusor smooth muscle cell subjected to the cyclic mechanical stretch].
AB  - OBJECTIVE: To investigate the relationship between phenotype transformation and
      biomechanical properties of detrusor smooth muscle cell (DSMC) subjected to the
      cyclic mechanical stretch. METHODS: Cultured rat DSMCS were grown on collagen
      coated silicone membranes and subjected to continuous cycles of stretch
      relaxation. All experiments were made on cells between passage 2 and 4. Each
      cycle consists of 5-second stretch and 5-second relaxation. The computer
      controlled vacuum induced 10% (I), 20% (II) and 30% (III) maximum elongation of
      the plate membrane at different designed pressures. We assessed DNA synthesis
      rate using tritiated thymidine incorporation assay. Using immunofluorescent assay
      and flow cytometer, we analysed the expression of SM-alpha-actin and
      proliferation of DSMC. The image analysis and micropipette aspiration systems
      were employed to investigate the single cell contraction and viscoelasticity. The
      elastic modulus K(1), K(2) and viscoelastic coefficient micro were determined
      using the three-element standard linear solid model, thus demonstrating the
      passive deformation ability of detrusor cells. RESULTS: As the basic structural
      changes to mechanical stretch, DSMCs underwent phenotypic modulation from their
      normal contractile phenotype to a "synthetic" phenotype: the DSMCs became more
      proliferative and the actin less organized along the cell's long axis. The cell
      proliferation index (CPI) of control and stretched group (10%, 20%, 30%
      elongation) were 0.24, 0.43, 0.58 and 0.65 respectively. After mechanical
      stretch, the well-spread filaments changed their orientation. Contraction and
      viscoelasticity of single DSMC subjected to stretch both decreased significantly
      compared to control. The Vmax and. DeltaLmax of group III (30% elongation) saw
      significant decreases compared with unstretched control (P < 0.01). K(1) and K(2)
      decreased with the increasing of mechanical overload, however, there was no
      statistic difference between groups II and group III. CONCLUSIONS: Structure
      determines function. Conversely, dysfunction implies the structural
      transformation. Functional abnormalities of BOO have the structural basis:
      phenotype transformation of detrusor cells. Cyclic stretch and relaxation applied
      to DSMCs in vitro can be used to model the increases in urodynamic load
      experienced by the bladder detrusor muscle under the conditions of bladder outlet
      obstruction. Phenotypic transformation is the structural basis of functional
      changes of DSMC subjected to periodic overload mechanical stretch.

PMID- 14728830
TI  - [Pathogenicity and treatment of acute respiratory distress syndrome after
      thoracotomy].
AB  - OBJECTIVE: To investigate the causes of acute respiratory distress (ARDS) after
      thoracotomy and to find out the measures to prevent ARDS. METHODS: The
      characteristics of incidence, pathogenicity and treatment of ARDS after
      thoracotomy in 31 patients were analysed. RESULTS: The patients who had chronic
      obstructive pulmonary disease, long history of smoking, hypertension were prone
      to ARDS. Injury to lung in operation, shock and pulmonary infection probably
      caused ARDS. Clearing away respiratory tract secretion, preserving of a clear
      airway, controlling pulmonary infection, alleviating pneumonedema by diuresis,
      early executing tracheotomy or mechanic assistant ventilation by
      tracheointubation were keys to rescuing patients successfully. CONCLUSIONS: It is
      suggested that multi factors were related to ARDS after thoracotomy. Shock,
      injury to lung in operation, pulmonary infection, are important factors that lead
      to post-operative ARDS after thoracotomy. Early treatment can reduce mortality of
      ARDS.

PMID- 14728831
TI  - [Early postoperative pulmonary function study: changing curve and influencing
      factors analysis].
AB  - OBJECTIVE: To investigate the changes and influence factors for early
      postoperative pulmonary function of thoracotomy. METHODS: Pre- and early
      postoperative pulmonary function was detected in 64 consecutive cases with
      optimal thoracotomy. Pain assessment was conducted before pulmonary function
      test, and the chief complaints of patients were recorded after the procedure. The
      changing curves of pulmonary function were made and the differences associated
      with groups, surgical styles, pain assessment, epidural analgesia, chief
      complaint and preoperative conditions were analyzed using SPSS10.0 medical
      statistic software. RESULTS: Pulmonary function was severely lowered to (39 +/-
      14)% of the base line on the first day. It was rehabilitated gradually, and
      recovered to (62 +/- 10)% of the base line on the 8th day. Epidural analgesia
      could improve pain relaxation and pulmonary function in some degree. Single
      factor analysis showed that postoperative pain, postoperative day and surgical
      style were the significant influence factors for early postoperative pulmonary
      function. Multiple-factor analysis showed that preoperative pulmonary function,
      age and postoperative pain were the main factors, while surgical style had only
      weak effect on it. CONCLUSIONS: Early postoperative pulmonary function is
      severely impaired by thoracotomy. It rehabilitate gradually with time.
      Improvement of preoperative pulmonary function, reducing surgical procedure
      injuries, especially injury to respiratory muscle system, and enough
      postoperative pain relief are the most important means that will reduce pulmonary
      function impairment and consequently reduce postoperative pulmonary
      complications.

PMID- 14728832
TI  - [Preliminary research of the relationship between overexpression of facilitative
      glucose transporter-1 and fluorodeoxyglucose uptake in primary human lung
      squamous cell carcinoma].
AB  - OBJECTIVE: To assess the relationship between the overexpression of facilitative
      glucose transporter-1 (Glut1) and fluorine-18 fluorodeoxyglucose (FDG) uptake in
      patients with primary lung squamous cell carcinoma. METHODS: From April 1999 to
      March 2001, 23 patients with lung squamous cell carcinoma were imaged using FDG
      positron emission tomography (PET) before surgery. Their maximum and mean
      standard uptake values (SUVmax and SUVmean) of tumor and SUV of the normal lung
      (SUVlung) were measured. The expression of Glut1 of all the 23 cases was analysed
      in paraffin sections using SP immunohistochemistry. RESULTS: All the 23 tumors
      tested were Glut1 positive (69 +/- 18)% of tumor cell area was positive and
      staining intensity was 4.6 +/- 0.7. All tumors of the patients could be detected
      by FDG-PET. FDG uptake of tumor was higher than that of normal lung (P < 0.01).
      SUVmax, SUVmean and SUVlung were 8.33 +/- 4.14, 6.10 +/- 3.00 and 0.38 +/- 0.13
      respectively. Correlations were found among Glut1 expression and FDG uptake and
      tumor size (P < 0.01). CONCLUSIONS: (1) Glut1 overexpression is universal in the
      lung squamous cell carcinoma. (2) SUV was higher in the lung squamous cell
      carcinoma than that of the normal lung tissue. (3) Glut1 expression and FDG
      uptake and tumor size appear to be correlated with each other in patients with
      lung squamous cell carcinoma.

PMID- 14728833
TI  - [Left ventricular aneurysmectomy with geometric reconstruction].
AB  - OBJECTIVE: To summarize the experience in performing left ventricular
      aneurysmectomy (LVA) with geometric reconstruction and concomitant coronary
      artery bypass grafting (CABG) without mortality. METHODS: Forty-two patients
      underwent LVA with geometric reconstruction and concomitant CABG. Forty-one
      patients were male, one was female with mean age of (55.5 +/- 2.4) years (40 - 68
      years). Preoperative cardiac function was NYHA class III in 32 patients and class
      IV in 10. Thirty-eight patients had unstable angina pectoris and 10 had the
      history of severe ventricular arrythmia. Eight patients had ventricular
      tachycardia. Preoperative left ventricular ejection fraction (LVEF) was 41% (17% 
      63%), LVEF was less than 40% in 29 cases. Left ventricular anatomic aneurysms
      were confirmed by ventriculography. Thirty-three cases underwent Jatene
      technique; 8 cases, Dor technique, and 1 case, Cooley technique. Mural thrombi
      were found in 21 patients and were completely removed. CABG was concomitantly
      performed in all patients. All of the left anterior descending artery was
      bypassed with left internal mammary artery and the other target vessels with
      saphenous vein. Mean cardiopulmonary bypass time was (135 +/- 11) minutes and
      aortic clamping time was (78 +/- 10) minutes. RESULTS: No hospital mortality
      occurred and all patients were discharged. Postoperative reexploration for
      bleeding in 1 patient. The diameter and end systolic and diastolic volume of left
      ventricle were significantly decreased to nearly normal after operation.
      Operative ejection fraction had a tendency to increase but without significance
      (P > 0.05). CONCLUSIONS: LVA with geometric reconstruction and concomitant CABG
      could not only improve heart function but also eliminate ventricular arrythmia.
      The clinical result was excellent.

PMID- 14728834
TI  - [Treatment of posterior-communicating wide-necked aneurysms with endovascular
      stent and Guglielmi detachable coils].
AB  - OBJECTIVE: To summarize our clinical experience in treating posterior
      communicating wide-necked aneurysms using endovascular stent and Guglielmi
      detachable coils (GDCs). METHODS: The coronary stents were implanted across the
      neck of 32 posterior-communication wide-necked aneurysms. Microcatheters were
      introduced into the aneurysm sac through stent mesh, GDCs were used to embolize
      aneurysms. RESULTS: All operations were successful. Total occlusion was achieved
      in 26 patients, over 90% in 4, 60 - 70% in 2. The patients were perfectly
      recovered with patency of the parent arteries. CONCLUSION: Endovascular therapy
      combined with stent implatation and GDC placement is a valid approach to the
      treatment of posterior-communication wide-necked aneurysms.

PMID- 14728835
TI  - [The change of blood supply pattern in visceral arteries of Stanford B dissection
      after endovascular repair].
AB  - OBJECTIVE: To discuss the change of blood supply pattern in visceral arteries of
      Stanford B dissection. The visceral arteries include celiac trunk (CA), superior
      mesenteric artery (SMA) and renal artery (RA). METHODS: By retrospectively
      analysing the clinical data of 52 cases with Stanford B dissection, the blood
      supply pattern of visceral arteries was confirmed by aortography and the changes
      before and after endovascular repair were compared. RESULTS: After repair: the
      stenosis lesions disappeared in 7 cases supported by true channel completely but
      one. Twenty-two visceral arteries supported by true and false channel
      simultaneously recovered true channel chiefly but one. One recovered true channel
      chiefly and one had no change in 2 visceral arteries supported by false channel
      completely. Four recovered true channel chiefly and one had no change in 5
      visceral arteries without blood support. 88.9% blood support got better and 11.1%
      blood support had no change in 36 damaged visceral arteries after endovascular
      repair. CONCLUSION: Blood support from true and false channel simultaneously is
      the chief pattern in the injured visceral arteries before repair; Endovascular
      repair technique is benefit to recovering the blood support of true channel.

PMID- 14728836
TI  - [Clinical significance and correlation between elevated serum TR6 and lympho
      metastasis in gastric cancer].
AB  - OBJECTIVE: To evaluate the value of serum TR(6) for the diagnosis and TNM
      classification in patients with gastric carcinoma. METHODS: Serum TR(6) levels
      were measured using ELISA method in 31 gastric cancer patients, 19 patients with
      nonmalignant conditions and 29 healthy individuals. TR(6) expression in tumor
      mass was studied with immunohistochemistry. TR(6) gene copy number in tumor
      tissues was evaluated by real time PCR. RESULTS: Ninety-seven point nine percent
      (47 of 48 cases) of healthy individuals and patients with nonmalignant conditions
      were serum TR(6)-negative. In contrast, 71% (22 of 31 cases) of gastric cancer
      patients were serum TR(6)-positive. Serum TR(6) positiveness was closely
      correlated with tumor differentiation status and TNM classification. TR(6) gene
      amplification did not occur in gastric carcinoma. CONCLUSIONS: Serum TR(6) levels
      were correlated significantly with TNM stage and histopathological type of tumor.
      This can help to determine the pre-operative TNM classification and to choose the
      optimal extent of lymph node dissection for gastric cancer.

PMID- 14728837
TI  - [The application of ultrasonography to estimate blood vessel injury of upper
      limbs sustaining electric burns].
AB  - OBJECTIVE: To explore a new method in estimating extent and degree of arterial
      injury in upper limbs sustaining high tension electric burns. METHODS: Eighteen
      patients (twenty-four upper limbs) with high tension electricity injury were
      admitted from December 1998 to September 2002, The damaged limbs consisted of
      four parts: wrist wound part, 5 cm, 10 cm, 15 cm parts around wrist wound, where
      the radial and ulnar arteries were detected using B ultrasound and color WP
      Doppler examination. The changes of endangium, vessel diameter, thickness of the
      vessel wall and volume of blood flow were recorded respectively. The parameters
      of normal radial and ulnar arteries were also determined as normal control.
      RESULTS: B ultrasound and color WP Doppler examination showed that the endangium
      in radial and ulnar arteries become coarse, edema or exfoliation. The vessel wall
      was thicker than that of the normal control and the thickness was heterogeneity.
      The vessel wall could be necrosis in severe patient and the vessel cavity was
      stricture or beaded. Thrombosis or occlusion could occur at the site of severe
      injury area in vessel. The decrease in volume of blood flow was observed. The
      condition of the radial and ulnar arteries become well apart from 10 - 15 cm of
      wrist wound. CONCLUSIONS: The ultrasonography can be used to detect the changes
      in endangium, diameter, thickness of the vessel wall, blood flow volume in injury
      blood vessel caused by electric burn injury. It is helpful in judging the degree
      and extent of injury vessel and could be a safe, non-invasive diagnostic method
      and is worth popularizing.

PMID- 14728838
TI  - [Expression and significance of substance P, neurofilament-H in glomus tumors
      with chronic pain].
AB  - OBJECTIVE: To observe the expression and distribution of substance P (SP),
      neurofilament-H (NFH) in glomus tumors with chronic pain, and to discuss the
      process of chronic pain and the relationship with pain degree. METHODS: Twenty
      seven patients diagnosed as glomus tumor with chronic pain were enrolled as case
      group, and divided into light pain symptomatic group (LPSG) (n = 12) and severe
      pain symptomatic group (SPSG) (n = 15) according to clinical manifestations.
      Control group (CG) were enrolled by 30 patients with amputated extremities or
      hands after trauma. Immunohistochemical methods were used to determine the
      expression of SP, NFH which were detected quantitatively by computer graph
      analysis system too. RESULTS: The positive expression and distribution of SP, NFH
      existed in all the three groups and SPSG expression level was the highest
      [Grayscale Value(SP) (143.3 +/- 7.5), Grayscale Value(NFH) (167.7 +/- 4.4)], LPSG
      followed [Grayscale Value(SP) (156.2 +/- 8.2), Grayscale Value(NFH) (194.8 +/-
      4.0)], control group was the third [Grayscale Value(SP) (208.2 +/- 16.6),
      Grayscale Value(NFH) (225.1 +/- 8.3)]; The difference of expression level among
      three groups was significant [SPSG vs LPSG (P(SP) = 0.002, P(NFH) < 0.0001), SPSG
      vs CG (P(SP) < 0.0001, P(NFH) < 0.0001), LPSG vs CG (P(SP) < 0.0001, P(NFH) <
      0.0001)]. The findings of Pearson product-moment correlation analysis between
      quantitative grayscale value of SP, NFH respectively and pain score in all the
      patients with glomus tumor showed linear negative correlation (r(SP) = -0.8974,
      P(SP) = 0.000001; r(NFH) = -0.6545, P(NFH) = 0.000212). CONCLUSION: SP is the
      mainly afferent pain transmitter in the process of chronic pain in glomus tumor,
      and NFH plays an important role in pain-transmitted activities.

PMID- 14728839
TI  - [Experimental studies on adriamycin alginate-chitosan microcapsules in the
      treatment of rabbit VX2 carcinoma in the extremity].
AB  - OBJECTIVE: To study the effects of chemoembolization with adriamycin alginate
      chitosan microcapsules in the treatment of VX2 carcinoma in the extremity of the
      rabbit. METHODS: Twenty-four New Zealand white rabbits transplanted with VX2
      carcinoma cells into the muscle tissue of the lower right thigh were divided into
      four groups namely groups A, B, C and D, and received regional infusion from
      femoral artery. Each group consisted of six rabbits: a group given natural saline
      (Group A), a group given adriamycin (Group B), a group given blank alginate
      chitosan microcapsules (Group C) and a group given adriamycin alginate-chitosan
      microcapsules (Group D). Three days after treatment, all groups were examined by
      histology and immunohistochemical detection (TdT-mediated dUTP nick end labeling
      technique, TUNEL; proliferating cell nuclear antigen, PCNA). RESULTS: The blood
      vessels of the tumor were almost embolized by the microcapsules. Extensive
      necrosis, high level of positive cells in TUNEL (60.85% +/- 5.21%) and low level
      in PCNA detection with in the tumors were observed in Group D. CONCLUSION:
      Adriamycin alginate-chitosan microcapsules can potentially play roles in two
      respects, 1 to serve as embolizing agents, and 2 to serve as drug delivery
      vehicles for local release. Chemoembolization with microparticals is an effective
      treatment of malignant osseous and soft tissue sarcomas in an experimental model.

PMID- 14728840
TI  - [Effects of intervening measures on postpartum depression].
AB  - OBJECTIVE: To study the related factors of postpartum depression (PPD) and the
      effects of intervening measures to PPD incidence. METHODS: 1 597 pregnant women
      selected from our antenatal care clinic were investigated by using the hospital
      anxiety and depression questionnaire (HAD) during pregnancy and the Edinburgh
      postpartum depression scale (EPDS) after childbirth. All the enrolled women were
      randomly divided into control group and intervening group by the proportion of 1
      to 2. Six intervening measures were used in the latter group. RESULTS: (1) There
      were 49 women whose HAD >or= 11 score (anxiety-depression mood) with 28 cases
      (57.1%) had got postpartum depression in the control group. In the intervening
      group, however, there were 94 women whose HAD >or= 11 score with 24 cases (25.5%)
      had got postpartum depression. There is a significant difference between the two
      groups (P < 0.01). (2) There were 71 (13.0%) women whose EPDS >or= 13 score
      (postpartum depression) in the control group. In the intervening group, however,
      there were 63 (6.0%) women whose EPDS >or= 13 score. There had a significant
      difference between the two groups (P < 0.01). (3) PPD women had higher N and P
      scores than those of non-PPD women (P < 0.01). CONCLUSION: (1) Prenatal anxiety,
      depression, negative personality and postpartum psychological and physiological
      changes were high risk factors to PPD. (2) Psychological personality play an
      important role in PPD. (3) Incidence of PPD was significantly reduced by social
      support.

PMID- 14728841
TI  - [Changes and significance of orphanin and serotonin in patients with postpartum
      depression].
AB  - OBJECTIVE: To study the changes of orphanin (OFQ) and serotonin (5-HT) in the
      patients with postpartum depression (PPD). METHODS: Twenty one patients with
      postpartum depression (PPD group) and 25 healthy lying-in women (control group)
      were studied. The concentrations of plasma OFQ were measured by radioimmunoassay.
      The levels of 5-HT were measured with high-pressure liquid chromatography with
      electrochemical detector. RESULTS: (1) The levels of plasma OFQ in PPD group were
      (28.5 +/- 5.8) ng/L, in control group, the levels of OFQ was (10.4 +/- 3.7) ng/L,
      the levels of OFQ in PPD group were significantly higher than that in the control
      group (P < 0.01). (2) The levels of plasma 5-HT in PPD group and control group
      were (1.0 +/- 0.3) micro mol/L and (1.4 +/- 0.4) micro mol/L respectively, the
      levels of 5-HT in PPD group decreased significantly (P < 0.05). (3) In the PPD
      group, there was a significant negative correlation between the OFQ and 5-HT
      level (P < 0.05). CONCLUSION: The PPD was associated with OFQ and 5-HT, the
      changes of OFQ levels may play an important role in the pathogenesis of the PPD.

PMID- 14728842
TI  - [Evaluation of the glucose screening retest during pregnancy].
AB  - OBJECTIVE: To evaluate of the glucose screening retest for gestational diabetes
      mellitus (GDM) during pregnancy. METHODS: A retrospective analysis of 714
      pregnant women screened for GDM, between December 1, 2001, and December 31, 2002,
      was performed. The first glucose challenge test (GCT) was performed in 16 - 27
      week and retested in 28 - 38 week. Diagnosis of GDM was based on the criteria of
      Dong. NDDG criteria was also discussed. RESULTS: (1) 1-hour glucose value of 50 g
      GCT >or= 7.8 mmol/L was set as abnormal. The first 50 g GCT abnormal rate was
      26.6% (190/714), and the retest abnormal rate was 35.2% (225/639). The mean age
      of pregnant women in 50 g GCT positive group was significantly higher than that
      in the negative group (P < 0.05), but there was no significant difference in
      family history and body mass index (BMI) between the two groups. Both the mean
      birth weight and the incidence of macrosomia of second 50 g GCT abnormal group
      were significantly higher than those in the normal group (P < 0.05). (2) By the
      criteria of Dong, 28 women were found to have GDM and 40 have IGT (impaired
      glucose tolerance) by the first 50 g GCT. New added cases included 15 GDM and 27
      IGT by the retest 50 g GCT. By NDDG criteria, 14 GDM and 24 IGT cases were
      diagnosed by the first 50 g GCT, 5 GDM and 14 IGT cases by retest GCT. (3) The 1
      hour blood glucose value [(7.3 +/- 1.6) mmol/L] in second 50 g GCT were
      significantly higher than those in first 50 g GCT [(6.9 +/- 1.8) mmol/L]. The
      results of 50 g GCT of two times were consistent in 68.1% women (normal/normal
      and abnormal/abnormal). There were 376 (52.7%) women whose 1-hour glucose value
      of the first 50 g GCT <or= 6.8 mmol/L. Among them neither GDM nor IGT were found
      by retest GCT. If the 1-hour glucose value of first 50 g GCT < 7.8 mmol/L (n =
      524), there were 4 cases GDM and 17 cases IGT by the criteria of Dong by retest
      of 50 g GCT, but no GDM and only 7 cases IGT were found by NDDG criteria.
      CONCLUSIONS: (1) Screening for GDM should be done for all pregnant women
      especially in big city. (2) If the NDDG criteria were used, the retest should be
      done for the women whose first 50 g GCT >or= 7.8 mmol/L, and the 75 g OGTT should
      be done directly. (3) Maternal age appears to be the most important risk factor
      for GDM.

PMID- 14728843
TI  - [Study of morphological changes in levator ani muscle of patients with stress
      urinary incontinence].
AB  - OBJECTIVE: To observe the the histological changes of levator ani muscle in
      patients with stress urinary incontinence (SUI) or pelvic organ prolapse (POP)
      and to determine the alteration that contributed to pathogenesis. METHODS: Biopsy
      specimens of levator ani muscle were obtained from 15 patients with SUI, 19
      patients with POP and 3 asymptomatic control with rectal cancer during operation.
      Levator ani muscle's structure was examined with routine histological techniques.
      At the same time, fiber distribution and diameters were also measured. RESULTS:
      The morphological features of levator ani muscle in SUI and POP group included
      the muscular fiber density decreased and separated by large amounts of dense
      connective tissue. The mean diameter of levator ani muscle in 4 SUI patients
      containing striated muscle fibers was (24 +/- 9) micro m, the mean diameter in 3
      POP patients was (24 +/- 5) micro m, and the mean diameter in 3 control cases was
      (54 +/- 11) micro m. There was no diameter difference between SUI and POP group
      (P > 0.05), and the mean fiber diameters of SUI and POP patients were
      significantly smaller than that of the control group (P < 0.05). The proportion
      of type I fibers in SUI and POP patients had the tendency to increase (79.6%,
      97.2% and 77.2%), with relative decrease of type II fibers. In control group the
      mean diameter of muscle fiber decreased significantly with age and menopausal
      time (P = 0.000). CONCLUSIONS: There was obvious fibrosis and the muscle fiber
      atrophy in SUI and POP group, which resulted in the weakness of pelvic floor. The
      prevalence of type I fibers might be disadvantage to forceful contraction during
      straining. Aging also contributed to neuromuscular degeneration and then
      associated with urinary incontinence in elderly women.

PMID- 14728844
TI  - [Analysis of risk factors about stress urinary incontinence in female].
AB  - OBJECTIVE: The aim was to assess the prevalence of stress urinary incontinence
      (SUI) in community dwelling women and to assess the relationship between the
      various risk factors and this disease. METHODS: Selecting the community of Gulou
      at random and sending questionnaires to 6,066 women who living there. The
      questionnaire was designed to investigate the lower urinary tract symptoms,
      especially urinary incontinence. The questionnaire included some questions such
      as: age, weight, occupation, the level of education, menopause pregnancy and
      delivery, delivery through vagina or by cesarean section, the maximum body weight
      of fetus, chronic disease (hypertension, diabetes mellitus, cough, constipation),
      operation in abdomen and pelvis, the behaviour of life (smoking, alcohol abuse,
      exercise), the prevalence and frequency of urinary incontinence, the quality of
      life and the recognition of this disease. RESULTS: The collecting rate was 92.1%
      (5,587/6,066). The prevalence of urinary incontinence was 18.1% and the
      prevalence of SUI was 8.8%. Age (OR: 1.010, 95% CI: 1.001 - 1.025), higher body
      mass index (OR: 1.092, 95% CI: 1.054 - 1.132), hypertension (OR: 2.342, 95% CI:
      1.026 - 5.349), constipation (OR: 1.448, 95% CI: 1.216 - 1.725), multiple
      abortion (OR: 1.306, 95% CI: 1.113 - 1.533), multipara (OR: 1.205, 95% CI: 1.009 
      1.440), using abdominal pressure in laboring (OR: 1.684, 95% CI: 1.140 - 2.489),
      straight cutting of perineum (OR: 2.244, 95% CI: 1.162 - 4.334), perineum tear
      (OR: 2.576, 95% CI: 1.724 - 3.851), infection of perineal incision (OR: 5.988,
      95% CI: 1.936 - 18.616) were risk factors of SUI in women. CONCLUSION: Many risk
      factors can cause urinary incontinence, among them age, pregnancy and childbirth
      are most important ones.

PMID- 14728845
TI  - [Research on repairing patterns and factors causing subsequent surgery after
      trancervical resection of endometrium].
AB  - OBJECTIVE: To study the repairing process and the factors causing subsequent
      surgery after trancervical resection of endomitrium (TCRE). METHODS: From March
      1991 to September 2002, 1 431 hysteroscopic endometrium resection procedures were
      performed in Hysteroscopic Center of Fuxing Hospital, and 38 patients who
      required additional treatment which include 13 hysterectomy, 3 repeat TCRE and 22
      uterine curettage were collected and the specimens were stained by hemaloxylin
      eosin, Masson's trichrome and respiratory enzyme dehydronicotinamide adenine
      dinucleotide phosphate diaphorase as well as proliferative cell nuclear antigen
      (PCNA) respectively to evaluate the tissue healing process and the
      histopathological changes. Some of the changes were observed by electron
      microscope. RESULTS: (1) The superficial myometrium presented necroses and
      granulationingitis in the early stage and then scar formation in the later stage
      followed TCRE. (2) The granulation structure was covered with columnar epithelial
      cell and the smouth muscle cell regrowth which showed positive reaction by PCNA
      staining below the scarred tissue. (3) The undestroyed glands of endometrial
      floor were showed both inside granulation and scar tissue where lymphocytes
      infiltration and a great deal of foreign-body giant cells were also found. Focal
      and diffuse endometrium regeneration located beside these granulation and scar
      structure. (4) Adenomyosis presented in some of uterine specimens, but the cycle
      endometrium and inflammatory granulation tissue presented in the uterine
      curettage tissue. CONCLUSIONS: The repairing patterns of destroyed myometrium are
      mainly based on granulationingitis and scar formation followed TCRE procedure,
      endometrial glands and smooth muscle cells regrowth are also involved in this
      process. Endometrium regeneration, adenomyosis and inflammation are the main
      reasons caused subsequent surgery.

PMID- 14728846
TI  - [Endocrine and metabolic effects of metformin in combination with compound
      cyproterone acetate in women with polycystic ovarian syndrome].
AB  - OBJECTIVE: To study the endocrinologic and metabolic effects of metformin in
      combination with compound cyproterone acetate (CPA) on patients with polycystic
      ovarian syndrome (PCOS). METHODS: A prospective study involved total 45 PCOS
      patients as group A and 20 non-PCOS infertility patients as control (group B).
      Complete baseline work-up including body mass index (BMI), waist/hip ratio (WHR),
      ferriman-Gallwey score (FGS), gonadotrophin, testosterone (T), sex hormone
      binding globulin (SHBG), dehydroepiandrosterone sulfate (Ds), insulin (FI) and
      glucose tolerance test, were performed in all patients. Patients in group A were
      treated with CPA alone (group A1), metformin alone (group A2) or combination of
      CPA with metformin (group A3), respectively by randomization. At the end of 12
      week therapy, subjects were re-evaluated and above parameters were measured.
      RESULTS: Women in group A had significant increases in BMI, WHR, FGS, luteinizing
      hormone (LH), T, FI, insulin resistance, and significantly decrease in high
      density lipoprotein (HDL)-C comparing with the control group (P < 0.01). No
      significant difference among A1, A2 and A3 was found at baseline. LH, T, free
      testosterone (FT) were significant decreased from (13.9 +/- 5.9) IU/L, (2.1 +/-
      0.8) nmol/L and (2.8 +/- 2.3) nmol/L respectively to (5.8 +/- 2.2) IU/L, (1.2 +/-
      0.4) nmol/L and (0.8 +/- 0.5) nmol/L respectively and SHBG was significant
      increased from (99 +/- 42) nmol/L to (187 +/- 64) nmol/L in group A3, when
      compared with LH, T and FT from (13.8 +/- 7.6) IU/L, (2.2 +/- 1.1) nmol/L and
      (2.5 +/- 1.9) nmol/L respectively to (11.8 +/- 6.5) IU/L, (1.8 +/- 0.8) nmol/L
      and (1.7 +/- 1.0) nmol/L respectively and SHBG from (99 +/- 40) nmol/L to (120 +/
      51) nmol/L in group A2 (P < 0.05 approximately 0.001). HDL-C were significantly
      increased from (1.5 +/- 0.3) mmol/L to (1.8 +/- 0.3) mmol/L in group A3 comparing
      with HDL-C from (1.5 +/- 0.4) mmol/L to (1.6 +/- 0.4) mmol/L in group A1 (P <
      0.001). CONCLUSIONS: The PCOS patients treated with metformin in combination with
      compound cyproterone acetate may be more effective in inhibiting hyperandrogen
      and hypersecretion of LH than metformin alone and more obvious in improving lipid
      profiles than CPA alone.

PMID- 14728847
TI  - [Efficacy and side effects of methotrexate in the treatment of ectopic
      pregnancy].
AB  - OBJECTIVE: To study the efficacy and side effects of methotrexate with different
      protocols in the treatment of ectopic pregnancy (EP). METHODS: Total of 648
      patients who had EP and were treated only with MTX were analysed. Patients were
      divided into six groups according to protocol: Group 1, 100 mg intravenously
      (IV); Group 2, 100 mg, IV, followed by citrovorum factor; Group 3, 20 mg, IV
      every day for five days; Group 4, 20 mg intramusculary (IM) every day for five
      days; Group 5, 75 mg, IV; Group 6, 75 mg, IM. RESULTS: The rates of repeated MTX
      injection in group 1 - 6 because of inadequate decrease of hCG were 23.3%, 25.0%,
      21.4%, 20.6%, 24.4% and 22.4% respectively. Success rates were 87.4%, 85.4%,
      90.5%, 92.6%, 86.3% and 91.4% respectively. Rates of liver dysfunction were
      10.3%, 8.3%, 64.3%, 69.1%, 8.7% and 31.0%. CONCLUSION: Single-dose of 75 mg MTX
      IV injection may be the best regimen in the treatment of EP because of the same
      efficacy but the least side effects.

PMID- 14728848
TI  - [Preliminary study on pathway of follicle-stimulating hormone on human epithelial
      ovarian cancer cell proliferation].
AB  - OBJECTIVE: There is only a limited direct indication that gonadotropins play a
      role in the genesis and development of epithelial ovarian cancer (EOC). Follicle
      stimulating hormone (FSH) can enhance the growth of epithelial ovarian cancer
      cell in vitro. The research is to investigate the pathway of FSH action in
      epithelial ovarian cancer cell. METHODS: Epithelial ovarian cancer cell line
      OVCAR3 was transfected with FSH receptor cDNA expressing vector. The transfected
      cells that are sensitive highly to FSH stimulation were got, and named OVCAR3
      FSHR. Adding FSH to the cells, or treating the cells with protein kinase C (PKC)
      activator tetradenocanoyl phorbol acetate (TPA), PKC inhibitor tamoxifen (TAM) in
      meantime, methyl thiazolyl tetrazolium (MTT) method was used to study the
      proliferation of cells. RT-polymerase chain reaction was used to identity the
      mRNA expression of various PKC subtypes. Westernblot was for detection of protein
      expression of PKCalpha and phosphorylated PKCalpha. RESULTS: FSH can promote
      proliferation of OVCAR3-FSHR (1.9 folds). There is some increase in PKCalpha by
      the FSH stimulation. The phosphorylated PKCalpha expression were enhanced
      significantly too. Both the amount and activity of PKCalpha were increased in
      response to FSH. TPA and TAM suppress FSH-stimulated cell growth (60% and 47%).
      Meanwhile expression level of PKCalpha was decreased with the co-treatment of TPA
      or TAM and FSH comparing with treatment with FSH only. CONCLUSIONS: FSH promoted
      epithelial ovarian cancer cell proliferation through PKC pathway. It plays a role
      in the development of epithelial ovarian cancer.

PMID- 14728849
TI  - [Significance of serum/cerebrospinal fluid human chorionic gonadotropin ratio and
      prophylactic intrathecal therapy in patients with brain metastases of gestational
      trophoblast tumor].
AB  - OBJECTIVE: To evaluate the effect of serum/cerebrospinal fluid (CSF) ratio of
      human chorionic gonadotropin (hCG) in detecting brain metastases of gestational
      trophoblast tumor and the significance of prophylactic intrathecal therapy.
      METHODS: Clinical information of 44 patients with brain metastases (stage IV) and
      29 patients with lung metastases (stage III) of gestational trophoblast tumor who
      were admitted to our hospital between 1986 to 2001 were retrospectively analyzed
      by case control study. The variability of the ratio and the relationship between
      brain metastases was investigated, together with the effect of prophylactic
      intrathecal therapy. RESULTS: Serum/CSF hCG ratio in patients with brain
      metastases declined with time. The ratio before chemotherapy was in relevant with
      the size of the lesion which were less than 60 in advanced stages and more than
      60 in early stages. Patients of stage III with prophylactic intrathecal therapy
      did not progress to stage IV. CONCLUSIONS: Serum/CSF hCG ratio before
      chemotherapy could reflect the encephalic tumor load which had reference value in
      diagnosis and prognosis and prophylactic intrathecal therapy played an important
      role in preventing brain metastasis.

PMID- 14728850
TI  - [Recytoreductive surgery for recurrent epithelial ovarian cancer].
AB  - OBJECTIVE: To evaluate the role of recytoreductive surgery (RCRS) in recurrent
      epithelial ovarian cancer. METHODS: Fifty-five patients who underwent
      recytoreductive surgery at Peking Union Medical College Hospital between Nov.
      1998 and Apr. 2002 were retrospectively reviewed. They were divided into four
      groups firstly by the identity of recurrent lesion: group A, single lesion; B,
      disseminated lesion; C, intestinal obstruction; D, palliative surgery. Then they
      were divided into 3 groups according to the sensitivity to chemotherapy. Group A,
      diseases relapsed more than 6 months after chemotherapy; group B, relapsed less
      than 6 months; group C, relapsed during chemotherapy. We review the cases with
      regard to its macroscopic residual disease, complications of operation, cases
      with complete remission and partial remission, postoperation survival time and
      disease-free interval. RESULTS: Recytoreductive surgery for patients with
      isolated recurrent tumor were optimal. For those diagnosed as local lesion
      preoperatively, 61% of these cases were found to have disseminated diseases
      postioeratively. Sixty-five percents of these cases received optimal RCRS, but
      their prognosis were not as well as those with real isolated leasion (response
      rate: 36% vs 67%). Cases with different sensitivity to chemotherapy had different
      prognosis (response rate: A, 50%; B, 26%; C, 28%). CONCLUSION: Recytoreductive
      surgery should be considered in patients with isolated recurrent ovarian cancer
      and patient with recurrence more than 6 months after chemotherapy.

PMID- 14728851
TI  - [Diagnosis and treatment of recurrent epithelial ovarian carcinoma].
AB  - OBJECTIVE: To investigate the diagnosis, treatment and prognosis of recurrent
      epithelial ovarian carcinoma. METHODS: Fifty-two patients with recurrent
      epithelial ovarian carcinoma who were admitted in Zhongnan Hospital of Wuhan
      University between 1997 and 2002 were analyzed retrospectively, and their
      diagnostic methods and the survival rates were compared. RESULTS: The positive
      diagnostic rate of pelvic examination, CA(125) and ultrasound examination was
      73.1%, 84.6% and 53.8%, respectively to the recurrent epithelial ovarian
      carcinoma. The median survival time of group A (surgery + chemotherapy) and group
      B (chemotherapy) was 11 and 12 months, respectively. CONCLUSIONS: The diagnostic
      methods should include pelvic examination, CA(125) and ultrasound examination. We
      could not know the exact role of surgery to the management and prognosis of
      recurrent epithelial ovarian carcinoma. Chemotherapy may have an important role
      to the management and prognosis of recurrent epithelial ovarian carcinoma.

PMID- 14728852
TI  - [Role of positron emission tomography in diagnosis of recurrent ovarian cancer].
AB  - OBJECTIVE: To investigate the efficiency of positron emission tomography (PET)
      with (fluorine-18)-2-deoxyglucose ((18)FDG) in diagnosis of recurrent ovarian
      cancer. METHODS: (18)FDG-PET scanning and computerized tomography (CT) were
      performed on 31 patients 35 times, who were clinically free of disease after
      optimal cytoreductive surgery and first-line chemotherapy. Twenty-two patients
      were confirmed pathologically after second-look or re-debulking operation and the
      others were followed up by many methods (ultrasonography, CA(125) and pelvic
      examination combined), evaluating the role of PET and CT in the diagnosis of
      recurrent ovarian cancer. RESULTS: (1) PET demonstrated recurrent sites through
      increased (18)FDG uptake. In 35 times, PET showed 1 false-negative and 1 false
      positive cases. (2) The sensitivity of (18)FDG-PET is 96.3%, and CT is 70.4%.
      There was significant difference between two groups (P < 0.05). CONCLUSION: PET
      is more sensitive in diagnosing recurrent ovarian cancer than CT, so it improve
      early diagnosis in recurrent ovarian cancer.

PMID- 14728854
TI  - [Study on controlling the blood glucose level of gestational diabetes mellitus
      sufferer regularly during labor].
AB  - OBJECTIVE: To study the maternal blood glucose management of gestational diabetes
      mellitus during the labor and relationship of maternal blood glucose in labor and
      neonatal blood sugar. METHODS: A prospective study on maternal blood glucose
      monitoring and control during labor was carried in 40 pregnant women with
      abnormal glucose metabolism. We adjusted maternal blood glucose by low-dosage
      constant insulin drop during labor. RESULTS: Maternal blood glucose in labor
      arranged between 3.8 approximately 11.2 mmol/L, and low-dosage constant insulin
      drop was used in 17 cases (42.5%). The neonatal blood glucose was (4.0 +/- 1.5)
      mmol/L following delivery and (3.9 +/- 1.0) mmol/L at 24-hour postpartum. There
      were 2 cases with neonatal hypoglycemia. The neonatal blood glucose of the rest
      23 cases was (4.2 +/- 1.5) mmol/L, and (3.9 +/- 1.0) mmol/L at 24-hour
      postpartum, and 1 case with neonatal hypoglycemia. There was no the difference of
      the blood glucose level of newborns between mothers with abnormal glucose
      metabolism and the normal pregnant women. CONCLUSION: It is necessary to monitor
      and control the blood glucose level by low dose constant insulin during labor in
      pregnant women with abnormal glucose metabolism.

PMID- 14728853
TI  - [Related-factor analysis on efficacy of re-platinum chemotherapy in platinum
      sensitive recurrent ovarian carcinoma].
AB  - OBJECTIVE: To analysis the related factors of efficacy of re-platinum
      chemotherapy in platinum-sensitive recurrent ovarian carcinoma. METHODS: Forty
      one patients with platinum-sensitive recurrent ovarian cancer from Jan. 1998 to
      Oct. 2002 were reviewed, 37 factors were analyzed, including age, the optimal of
      primary surgery, number of chemotherapy cycles, standard chemotherapy or not,
      serum CA(125) level, follow up or not, relapse interval, the site and the number
      of relapse lesion, et al. RESULTS: Response rate of chemotherapy was 56%, the
      toxicity was not serious. Response rate of standard chemotherapy was 76% (19/25),
      not standard chemotherapy was 25% (4/16), standard chemotherapy or not was the
      only factor related to efficacy (P < 0.05). CONCLUSION: Re-platinum chemotherapy
      to platinum-sensitive recurrent ovarian carcinoma is reasonable, standard
      chemotherapy or not affects the response rate.

PMID- 14728855
TI  - [Study on the relationship between activin A, follistatin and preeclampsia].
AB  - OBJECTIVE: The purpose of this study was to determine the relationship of
      maternal serum activin A, follistatin and their mRNA expression in placenta with
      preeclampsia at term. METHODS: Twenty women with preeclampsia were enrolled in
      this study. Twenty healthy pregnancies matched for gestational ages were
      recruited as control group. Maternal serum activin A and follistatin in two
      groups were compared by using enzyme linked immunosorbent assay (ELISA).
      Placental tissues were obtained from preeclampsia and healthy control groups for
      analysis of activin A mRNA and follistatin mRNA expression by using quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR). Linear correlation
      analysis was used to explore the relationship between placental avtivin A mRNA
      and maternal serum activin A concentrations. RESULTS: (1) Maternal serum
      concentrations of activin A are significantly increased in preeclampsia group
      (33.7 +/- 6.6) micro g/L compared with control group (9.9 +/- 2.1) micro g/L (P <
      0.01). Maternal serum follistatin levels were not different between preeclampsia
      group (5.1 +/- 0.6) micro g/L and control group (4.7 +/- 0.3) micro g/L (P >
      0.05). (2) The placentas of preeclampsia group expressed activin A mRNA levels at
      significantly higher levels 1.11 +/- 0.21 than that of control group 0.61 +/-
      0.17 (P < 0.01). The expression of follistatin mRNA were not different between
      preeclampsia group 0.57 +/- 0.31 and control group 0.54 +/- 0.27 (P > 0.05). (3)
      In preeclampsia and control groups, maternal serum activin A concentrations had a
      significant positive correlation with activin A mRNA expression in placentas (r =
      0.89, P < 0.01). CONCLUSION: These results suggest that activin A is increased in
      women with preeclampsia, the elevated levels of activin A due to increased
      placental production.

PMID- 14728856
TI  - [Effects of ursodeoxycholic acid on the liver plasma membrane fluidity, hepatic
      glutathione concentration, hepatic estrogen receptors and progesterone receptors
      in pregnant rats with ethinylestradiol and progesterone induced intrahepatic
      cholestasis].
AB  - OBJECTIVE: To explore the effects of ursodeoxycholic acid (UDCA) on the fluidity
      of hepatic plasma membrane, glutathione concentration in liver, hepatic estrogen
      receptors and progesterone receptors in pregnant rats with ethinylestradiol and
      progesterone induced intrahepatic cholestasis. METHODS: sixty clean SD pregnant
      rats were selected and divided into three groups at random. Since the 13th day of
      pregnancy after taking blood, normal group was injected subcutaneously with
      refined vegetable oil 2.5 ml x kg(-1) x d(-1). Control group and treatment group
      were injected subcutaneously with the solution of progesterone 75 mg x kg(-1) x
      d(-1) and 17-alpha-ethynylestradio 1.25 mg x kg(-1) x d(-1) till the 17th day.
      Since the 17th day control group, normal group were fedwish 0.9% natriichloridi
      solution 5 ml x kg(-1) x d(-1); Treatment group was fedwish UDCA 50 mg x kg(-1) x
      d(-1) every day. On the 21th day, all rats were killed. Then the livers were
      collected for study. Membrane fluidity was measured by fluorescence polarization
      using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. Glutathione concentration
      was measured by 5,5'-dithionbis (2-nitrobenzoic acid) (DTNB). Estrogen receptors
      and progesterone receptors were measured by flow cytometry. RESULTS: (1) Hepatic
      plasma membrane fluidity and glutathione (GSH) concentration: significantly lower
      level of GSH concentration and higher fluorescence polarization (P) were detected
      in control group (GSH: 1.13 +/- 0.03, P: 0.149 +/- 0.008) in comparison with
      normal group (GSH: 2.11 +/- 0.07, P: 0.132 +/- 0.004, P < 0.05). However,
      Significantly higher level of GSH concentration and lower fluorescence
      polarization were detected in treatment group (GSH: 1.82 +/- 0.04, P: 0.141 +/-
      0.006) in comparison with control group (P < 0.05). The level of GSH
      concentration and fluorescence polarization were no difference between treatment
      group and normal group. Hepatic estrogen receptors (ER) and progesterone
      receptors (PR): The expression of ER and PR in control group (ER: 89.4 +/- 8.4,
      PR: 112.3 +/- 11.6) were higher than that of other two groups (P < 0.05). The
      expression of ER and PR in treatment group (ER: 56.4 +/- 7.5, PR: 70.1 +/- 9.3)
      were lower than that of control group (P < 0.05). But there was no difference
      between treatment group and normal group (ER: 39.5 +/- 7.3, PR: 59.6 +/- 7.4; P >
      0.05). CONCLUSION: Ursodeoxycholic acid may be effective drug in treatment
      intrahepatic cholestasis of pregnancy.

PMID- 14728857
TI  - [Changes of hypothalamus and peripheral orphanin in fetal rats with intrauterine
      ischemia and hypoxia].
AB  - OBJECTIVE: To evaluate the role of orphanin in the perinatal ischemia-hypoxia.
      METHODS: The concentration of hypothalamus and peripheral orphanin were measured
      by radioimmunoassay. Animal model of perinatal ischemia-hypoxia was set up by
      ligating uterine vessels. All the rats were delivered by cesarean section and
      scored according to respiration, heart beat, skin color, muscle tone and reflex
      after delivery. RESULTS: (1) The levels of orphanin in hypothalamus and
      peripheral blood in group B were (114 +/- 21) pg/g and (58 +/- 11) ng/L
      respectively. In group A, the were (71 +/- 14) pg/g and (31 +/- 7) ng/L
      respectively, the levels of orphanin in group B increased significantly when
      compared with the group A (P < 0.05). In control group, the levels of orphanin
      were (48 +/- 9) pg/g and (19 +/- 4) ng/L. The levels of orphanin in group A and B
      were significantly higher than those in the control group (P < 0.01, P < 0.05).
      (2) The Apgar scores in groups A and B were significantly decreased than that in
      control group (P < 0.01). The group A pups had significantly better scores than
      the group B (P < 0.05). CONCLUSION: The perinatal ischemia and hypoxia was
      associated with orphanin, the changes of orphanin levels may play an important
      role in the pathophysiological changes in perinatal ischemia and hypoxia.

PMID- 14728858
TI  - [Transvaginal follicular aspiration in follicle phase in the management of
      anovulation associated with polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the follicle development and pregnancy in clomiphene
      citrate-resistant patients with polycystic ovary syndrome (PCOS) after
      transvaginal follicular aspiration and gonadotropin administration. METHODS:
      Seventeen clomiphene citrate-resistant patients with PCOS failed to gonadotropin
      treatment associated with ovarian hyperstimulation syndrome (OHSS). They are
      anovulatory infertility with normal tubal and husbands' sperm condition. In this
      treatment regimen, all patients was administered with gonadotropin from day 5 of
      menstrual cycle (or withdrawal bleeding) and were asked to undergo ultrasound
      guided transvaginal follicular aspirations for 5 days later. Only one or two
      follicles for every ovary were remained and gonadotropin administration was
      continued. A follicle development, ovulation rate, pregnancy rate and sex hormone
      were monitored. RESULTS: Fifteen of the 17 patients experienced dominant
      follicles development and ovulation. 9 of them with one (52.9%), 4 with two
      (23.5%) and 2 with three (11.8%) dominant follicles ovulated and pregnancy
      occurred in 7 patients (41.2%). All of pregnancy are singleton. CONCLUSION: A
      single follicle development and singleton pregnancy can be realized in clomiphene
      citrate-resistant PCOS patients by combined ultrasound-guided transvaginal
      follicular asperation with gonadotropin administration.

PMID- 14728859
TI  - [Analysis of 174 cases with cervical cancer in women under 35 years old].
AB  - OBJECTIVE: To analyse the prevalence, etiology, presentation, preserving ovary
      and prognosis of cervical cancer in women under 35 years old. METHODS: The
      clinical information of 174 patients were retrospectively analysed. RESULTS: The
      percentage of new cervical cancer cases from 1991 to 2001 was 1.2%, 1.2%, 4.3%,
      4.2%, 4.6%, 4.5%, 7.3%, 9.0%, 10.7%, 9.4%, 10.8%, respectively (P < 0.01).
      Contact bleeding was the main symptom that occurred in 101 cases (101/174,
      58.0%). Cervicitis was incorrectly diagnosed in 45 cases (45/174, 25.9%). Sex
      irregularities occurred in 51 cases (51/174, 29.3%). The number of cases with
      carcinoma in situ, stage I, stage II, stage III was 22, 40, 94, 18, respectively.
      There are 29 cases with lymph vascular involvement, 60 with 1/2 or more
      penetration of the cervical stroma. The incidence of HPV16/18 infection was 34%.
      The ovarian metastasis was 0.8%. The 5 year survival rate of stage I - III was
      71.6%, 60.4% and 13.3%, respectively (P < 0.01). COX regression analysis
      indicated that stage, lymph-vascular involvement and the depth of tumor
      infiltration were independently prognostic factors. For patients with one risk
      factor after radical surgery, the survival of patients with adjuvant radiation
      therapy and chemotherapy or not was 100%, 88%, respectively (P > 0.05). For
      patients with two or more risk factors, it was 68%, 1/7, respectively (P < 0.05).
      CONCLUSIONS: There is an increasing prevalence of cervical cancer in women under
      35 years old, which is possibly related to the sexual transition. The preserving
      ovary in young cervical cancer patients is safe and effective. Patients with late
      stage, lymph-vascular involvement and deep infiltration of cervical stroma have
      poor prognosis. Adjuvant treatment may be helpful for patients with 2 or more
      risk factors after radical surgery.

PMID- 14728860
TI  - [Prenatal diagnosis and clinical management of a twin pregnancy consisting of a
      complete mole and coexisting fetus].
AB  - OBJECTIVE: To discuss the differential diagnosis of the hydatidiform mole and a
      coexisting fetus, to study the prenatal diagnosis and the clinical management of
      a twin pregnancy consisting of a complete mole and coexisting fetus (CMCF).
      METHODS: Two cases of CMCF were reported retrospectively. RESULTS: In the first
      case, the hydatidiform mole and a coexisting fetus was found by B mode ultrasound
      at the 10th gestational week, the patient asked to terminate the pregnancy. The
      interphase FISH and karyotype analysis of the normal villi and the mole showed
      both of them were diploid, thus the CMCF was diagnosed. In the second case, the
      hydatidiform mole and a coexisting fetus was found by B mode ultrasound at the
      21st gestational week. Transabdominal chorionic villi sampling and amniocentesis
      was performed, interphase FISH and karyotype analysis of the mole and the
      amniotic fluid showed both of them were diploid, thus the CMCF was diagnosed
      prenatally. The pregnancy was continued and premature rupture of membrane
      happened at the 28th gestational week, the cesarean section was performed. The
      neonate was healthy. The karyotype analysis of the placenta and the neonate was
      accordant with the prenatal diagnosis. CONCLUSIONS: As long as the hydatidiform
      mole and a coexisting fetus was found the prenatal diagnosis must be performed in
      order to differentiate the CMCF and the partial hydatidiform mole (PHM). The
      transabdominal chorionic villi sampling and the amniocentesis were ideal methods,
      interphase FISH and karyotype analysis of the mole and the amniotic fluid should
      be performed. If both of them were diploid, the CMCF could be diagnosed. The
      clinical management of CMCF should be done individually. If both of them were
      triploid, the PHM could be diagnosed.

PMID- 14728861
TI  - [Study on the association between maternal-infantile vertical transmission of
      hepatitis B virus and human leukocyte antigen DR gene domain].
AB  - OBJECTIVE: To study on the association between maternal-infantile vertical
      transmission of hepatitis B virus and human leukocyte antigen (HLA)-DR gene
      domain. METHODS: HLA-DR3, HLA-DR4, HLA-DR13, HLA-DR15 were detected by the
      technique of polymerase chain reaction-sequence specific primers (PCR-SSP) in
      maternal and neonatal blood of study group (78 cases) and control group (40
      cases). RESULTS: (1) In the pregnant women of study group, the gene frequency of
      HLA-DR3 was significantly higher than that in control group (P < 0.05), but the
      frequency of HLA-DR13 was significantly lower than those in control group (P <
      0.05), while the frequencies of HLA-DR4 and HLA-DR15 had no significant
      difference between the two groups (P > 0.05). (2) The pregnant women with high
      replication condition of HBV had significantly higher frequency of HLA-DR3 than
      those with low replication of HBV (P < 0.05). There was no significant difference
      of other phenotype between the two conditions. (3) The frequency of HLA-DR3 of
      pregnant women in intrauterine infection group was significantly higher than that
      of intrauterine non-infection group (P < 0.05). There had no significant
      difference of the frequencies of HLA-DR4, HLA-DR13, HLA-DR15 between the two
      groups (P > 0.05). The gene frequencies of HLA-DR3, HLA-DR4, HLA-DR13, HLA-DR15
      were found no significant difference between the neonates of the study group and
      the control group (P > 0.05). Although the gene frequency of HLA-DR3 (30.0%) in
      neonates of intrauterine infection group was higher than that of intrauterine non
      infection group (7.4%), but no statistical difference was found between the two
      group (P > 0.05). CONCLUSIONS: HLA-DR3 is positively correlated with chronic HBV
      carrying and high replication conditions of pregnant women. HLA-DR13 correlated
      negatively with chronic HBV carrying of the pregnant women. HLA-DR3 carriers of
      pregnant women and their fetuses have a susceptibility of HBV infection.

PMID- 14728862
TI  - [Apoptosis gene expression profiling of placental trophoblast cells in patients
      with pregnancy induced hypertension].
AB  - OBJECTIVE: To explore the function of placental trophoblast cell apoptosis on the
      pathogenetic mechanism of pregnancy induced hypertension (PIH). METHODS:
      Apoptosis of trophoblast cells in 20 cases of PIH (PIH group) and in 10 cases of
      normal pregnancy (control group) were directly observed using the terminal
      deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) method.
      Apoptosis gene expression patterns were screened with gene chip provided by
      Poxing Company, Shanghai. Standards for differently expressed genes were: (1) An
      absolute value of the natural logarithm of cy5 (PIH group)/cy3 (control group)
      greater than 0.69 with a difference of signal of cy5 2 times over that of cy3.
      (2) The signal value either cy3 or cy5 must be greater than 800. RESULTS: (1)
      TUNEL test showed that the number of trophoblast cells apoptosis per ten thousand
      micro m(2) was 1.584 in the PIH group and 0.032 in the control group with
      significant difference between the two groups (P < 0.01). (2) Ten differently
      expressed apoptosis genes were obtained through gene chip test (occupy 5% of
      total apoptosis gene in the gene chip). There was a significant decrease of
      apoptosis gene expression in all of PIH patient placental tissues (i.e a ratio of
      cy5/cy3 less than 1). Among them, there were genes that possess significant anti
      apoptosis functions (including SFRP(2), IAP(2), DHCY24 and ATPIA1). CONCLUSIONS:
      Remarkable apoptosis was found in placental trophoblast cells of PIH patients.
      Significant decrease in genes with anti-apoptosis functions can result in the
      apoptosis of placental trophoblast cells and thus contributes to the pathogenesis
      of PIH.

PMID- 14728863
TI  - [Analysis of the relative factors of the onset of repeated ectopic pregnancy].
AB  - OBJECTIVE: To determine the relative factors of the onset of repeated ectopic
      pregnancy. METHODS: The clinical data of the first time ectopic pregnancy of 28
      cases with repeated ectopic pregnancy were analysed, and compared with those of
      56 cases of non-repeated ectopic pregnancy onsetting at the same period. The
      factors measured included: age at onset of disease, age at first coitus,
      gravidity, parity, methods of contraception, duration of amenorrhea, duration of
      vaginal bleeding, serum beta-human chorionic gonadotropin level, volume of
      intraperitoneal bleeding, types of ectopic pregnancy, methods of therapy and
      inflammation evidence of fallopian tube. Logistic regression analysis was
      performed to determine the relative factors for onset of repeated pregnancy.
      RESULTS: The risk factors and its odds ratio (OR) from the multivariate analysis
      were as follow: anastomosis of the tube (62.74, P = 0.043), positive evidence of
      inflammation of the tube (54.85, P = 0.000), no contraception (11.29, P = 0.002),
      contraception by condom occasionally (4.75, P = 0.046); the protective factors
      and its OR were as follow: therapy being salpingectomy and sterilization of the
      opposite tube (0.06, P = 0.049), oral contraception (0.10, P = 0.050) and
      pharmacotherapy (0.33, P = 0.002). CONCLUSIONS: The risk factors of onset of
      repeated ectopic pregnancy include: anastomosis of the tube, positive evidence of
      inflammation of the tube, no contraception and contraception by condom
      occasionally; the protective factors include: therapy being salpingectomy and
      sterilization of the opposite tube, oral contraception and pharmacotherapy.

PMID- 14728864
TI  - [Clinical study of hysteroscopic surgery for endometrial polyps].
AB  - OBJECTIVE: To investigate the methods of different types of hysteroscopic surgery
      for endometrial polyps. METHODS: A total of 109 cases by different ways by
      hysteroscopic surgery for endometrial polyp from October 2000 to May 2002 were
      followed up. The mean age was 45 +/- 9 (26 - 73) years. The mean follow-up was 12
      +/- 5 (3 - 22) months. The patients of menstrual disorder were asked for filling
      in pictorial blood loss assessment chart (PBAC) before and after the surgery.
      RESULTS: By the PBAC there was significant difference between before and after
      the surgery (P = 0.001). After the surgery, among 84 polyps with menstrual
      disorder, 14 cases (16.7%) were amenorrhea, 26 cases (31.0%) spotting, other 24
      cases reducing the amount. Thirty-four cases that had had anemia recovered in one
      month after the surgery. In 16 cases dysmenorrhea, 7 cases were recovered, 7 got
      better, and the other 2 got worse. Of 5 cases of infertility (3 were primary and
      2 were secondary), 4 cases got pregnancy after the surgery. CONCLUSIONS: The
      polyp patient who had menstrual disorder without desire of fertility should
      undergo polypectomy with endometrial resection in order to avoid recurrence. The
      patient who has desire of fertility should undergo polypectomy merely. If she had
      polyp with polypoid hyperplasia she should undergo polypectomy with endometrial
      resection of superficial layer. The postmenopausal patient should perform
      polypectomy merely or polypectomy with endometrial ablation.

PMID- 14728865
TI  - [Establishment and characterization of a new squamous cell carcinoma cell line
      CS1213 from the human uterine cervix].
AB  - OBJECTIVE: To establish a human cervical carcinoma cell line. METHODS: A primary
      culture was initiated from malignant tissue collected by dissection of cervical
      biopsy specimens. Characterizing cells in culture which included morphological
      observation, biological and karyotypic analysis, experimental tumorigenesis and
      the expression of p53, bcl-2 and Ki67 genes was carried out. RESULTS: The new
      established cervical carcinoma cell line (CS1213) had been maintained in culture
      for over 170 generations. The cells which were nonadherent had a common, rounded
      appearance with a cell cycle time of 25-hour and a 19 colony formation rate in
      soft agar. Electron micrographs demonstrated abundant tonofilaments in the
      cytoplasm. The karyotype showed a hyperdiploid feature with a main chromosome
      stem number ranged from 80 to 88. The culture was not contaminated by mycoplasma
      and had a distinct lactic acid dehydrogenase isozyme pattern. High expression
      level of p53 (31.9%), bcl-2 (89.3%) and Ki67 (33.7%) proteins was detected by
      flow cytometry. The xenogeneic tumors were grown in nude mice with the
      histological structure of the original one. CONCLUSIONS: The novel CS1213 cells
      have the characteristics of human cervical squamous cells and could be used as an
      appropriate cellular model system for studying tumor invasion and metastasis.

PMID- 14728866
TI  - [Study on DNA polymerase beta gene mutation in human cervical cancer].
AB  - OBJECTIVE: To investigate whether DNA polymerase beta (POLB) gene mutations occur
      in human cervical cancer (CC). METHODS: To collect fresh specimens from 34
      cervical cancer and examine the mutation of POLB gene using reverse transcription
      polymerase chain reaction (RT-PCR), single strand conformation polymorphism
      (SSCP) analysis and sequence analysis. According to their histological grading,
      the 34 cases of CC were divided into three groups: 9 cases of grade I (G(1)), 14
      cases of grade II (G(2)), 11 cases of grade III (G(3)). RESULTS: POLB mutations
      were detected in the tissues of CC. The mutation of POLB is related with the
      histological differentiated of the CC. The mutated rates in low differentiated
      cancer were significantly higher than those in moderate and high ones, and the
      difference was significant (P < 0.05). The sequencing of the PCR product showed
      an A to G chang at nucleotide 660, which resulted in a substitution of the amino
      acid from arginine to glycin at codon 182. CONCLUSIONS: There were POLB mutations
      in the tissues of CC, and this may be related with the development of the CC. The
      mutations impaired the catalytic activity of POLB. As a result, this may lead to
      observed accumulation of mutations in tumor cells.

PMID- 14728867
TI  - [In vitro experimental study of gene therapy for ovarian cancer with thymidine
      kinase gene of herpes simplex virus mediated by a non-viral GE7 delivery system].
AB  - OBJECTIVE: To investigate gene transfer efficiency of a novel target non-viral
      vector GE7 and effects of herpes simplex virus thymidine kinase (HSV(1)
      tk)/ganciclovir (GCV) mediated by it in vitro. METHODS: The epidermal growth
      factor receptor (EGF-R) target gene delivery system GE7 was constructed. Human
      ovarian cancer cell line CAOV3 was transfected in vitro with beta-galactosidase
      (beta-gal) as reporter gene and HSV(1)-tk gene as therapeutic gene using this
      gene delivery system. By means of the assay of X-gal staining, Northern blotting,
      cell growth-inhibiting curve and so on, the transferring efficiency of exogenous
      genes and killing effects are observed. RESULTS: It showed that gene transfer
      efficiency is over 80%. When 10 mg/L GCV was put into ovarian cells transfected
      with HSV(1)-tk gene, 95% of cells were killed, and the apoptosis ratio reached up
      to 30. CONCLUSIONS: The GE7 gene delivery system is an effective and safe
      delivery system. GE7/HSV(1)-tk/GCV therapeutic gene system is appraising for
      ovarian cancer.

PMID- 14728868
TI  - [Study of effect of mifepristone on apoptosis of human ovarian cancer cell line
      3AO].
AB  - OBJECTIVE: To investigate the effect of mifepristone on the activity of
      proliferation and the apoptosis, the expression of estrogen receptor (ER),
      progesterone receptor (PR) protein and morphology changes of human ovarian
      carcinoma cell line 3AO and SKOV3 in vitro. METHODS: The proliferative activity
      of 3AO and SKOV3, which were cultured in vitro, was measured by tetrazolium-based
      colorimetric assay (MTT assay). Flow cytormetry (FCM) was used to measure the
      expressive rate of ER, PR, p53 protein, bcl-2 protein, cell apoptotic rate and
      cell proliferative cycle of 3AO cells, which were cultured with different
      concentration and duration of mifepristone. The morphologic and ultrastructure
      changes of apoptotic 3AO cells was observed by the light and electron microscopy.
      RESULTS: Mifepristone inhibited significantly the proliferation of 3AO cells in
      dose-time dependent manner in vitro. The inhibitory rate of 3AO cells growth,
      which were cultured with different concentration of mifepristone (5, 10, 20, 40,
      80 micro mol/L) and duration (24, 48, 72 h) was from 1.7% to 75.0% (P < 0.01),
      but the proliferation activity of SKOV3 cells in vitro had not significant
      changes (P > 0.05). 3AO cells apoptosis activity appeared the positive
      correlation with the dose of mifepristone and cultured duration (P < 0.01).
      Mifepristone blocked 3AO cells proliferative cycle at the G(0)-G(1) stage,
      decreased the cell radio of S stage. Mifepristone induced the apoptosis of 3AO
      cells in vitro. The light and electron microscopy demonstrated that 3AO cells
      cultured with mifepristone appeared typical morphological characteristics of
      apoptosis including the compaction and margination of the chromosomes, nuclear
      fragments and formation of apoptotic bodies. Mifepristone up-regulated
      significantly the expression of p53 protein, but down-regulated the expression of
      bcl-2 protein (P < 0.01). The expressive rates of p53 and bcl-2 proteins were
      (54.8 +/- 4.0)% and (10.1 +/- 1.2)%, respectively, when 3AO cells was cultured
      with mifepristone of 10 micro mol/L for 24 h. Compared with the expression rates
      of control group (27.1 +/- 3.3)% and (17.6 +/- 1.0)%, the difference was
      significant (P < 0.01). The expressive rate of PR protein of 3AO cells cultured
      with mifepristone of 10 micro mol/L for 48 h was (12.7 +/- 1.4)%, which was
      decreased compared with the expressive rate of control group (44.9 +/- 1.4)% (P <
      0.01). CONCLUSIONS: Mifepristone inhibited significantly the proliferation and
      induced the cell apoptosis of cell line 3AO in dose-time dependent manner in
      vitro. The anti-tumor effect was related to down-regulation the expression of PR
      protein and bcl-2 protein, and to up-regulation the expression of p53 protein of
      3AO cells.

PMID- 14728869
TI  - [Contraceptive efficacy of bioadhesive nonoxynol-9 Gel: comparison with nonoxynol
      9 suppository].
AB  - OBJECTIVE: To compare the contraceptive efficacy of a new spermicide, bioadhesive
      nonoxynol (N-9) gel, with a traditional N-9 suppository. METHODS: A total of 240
      child-bearing aged woman volunteers were randomly divided into two groups: 120
      cases using the gel for contraception, and another 120 using the suppository.
      Using lifetable method and log rank test, we compared the pregnancy rates and
      other discontinuation rates after follow-up for 6 months in two groups. RESULTS:
      No abnormal findings of cervical smears were detected before and after this
      clinical trial in all 240 women. The follow-up rates at 6 months were 100.0% and
      97.5% in the gel group and the suppository group, respectively. The 6-month gross
      cumulative pregnancy rates of typical use were 6.39 and 2.95 per 100 women (P >
      0.05), respectively. If we eliminated the 5 pregnancy women (3 in the gel group,
      and 2 in the suppository one), who did not consistently use the spermisides for
      every intercourse, the cumulative pregnancy rates at 6 month in perfect use would
      be 3.71 and 2.03 (P > 0.05). And the discontinuation rates due to allergy or
      other side effects at 6 months in typical use were 3.45 and 4.57 (P > 0.05),
      respectively. All of the results observed between two groups in this study were
      not statistically significant. CONCLUSION: The contraceptive efficacy of
      bioadhesive N-9 gel is as same as that of the N-9 suppository, and its clinical
      use is quite safe.

PMID- 14728870
TI  - [Changing trends of etiologic characteristics of cardiovascular diseases among
      inpatients in Shanghai: a retrospective observational study from 1948 to 1999].
AB  - OBJECTIVE: To investigate the trends in the change of etiologic types of
      cardiovascular disease among inpatients in Shanghai area from 1948 to 1999.
      METHODS: The retrospective estimate was based on the data survey in two major
      general hospitals of Shanghai. Descriptive statistics were provided for all
      patients meeting the inclusion criteria. Trend of percentage change was compared
      using linear regression. Diagnoses were categorized using the International
      Classification of Diseases, 9th Revision. RESULTS: (1) A total of 37 086
      admissions with different etiologic types of heart diseases from 1948 to 1999 was
      reviewed. The percentage of heart diseases among the inpatients in medical wards
      was significantly increased during this period, being 9.89%, 15.69%, 20.91%,
      23.54% and 24.24% (P < 0.05) for each decade respectively and reaching a peak in
      1990s. (2) Patterns of different etiologic types of heart diseases changed
      markedly from 1948 to 1999. The percentage of coronary heart disease increased
      from 6.78% in 1940s to 39.19% in 1990s (P < 0.05), cardiac dysrhythmias from
      0.63% to 18.84% (P < 0.05), cardiomyopathy from 0.05% to 5.01% (P < 0.05) and
      endocarditis from 0.02% to 0.69% (P < 0.05). The percentage of rheumatic heart
      disease decreased from 50.30% to 10.25% (P < 0.05). The percentage of
      hypertensive heart disease, myocarditis and congenital heart disease remained
      unchanged. (3) From 1948 to 1999 the overall in-hospital mortality of heart
      diseases in different decades decreased from 17.91%, 11.51%, 14.07%, 7.35% to
      2.39% (P < 0.05). (4) Patients were slightly younger in 1950s (39.7 +/- 5.5)
      years than those in 1990s (60.1 +/- 12.7) years (P < 0.05). (5) The percentage of
      male patients increased (ranging from 50.7% in 1940s to 62.4% in 1990s, P <
      0.05). CONCLUSIONS: Hospitalization patterns of heart diseases have changed
      dramatically in the second half of the last century in Shanghai. Coronary heart
      disease is the most frequent condition requiring hospitalization nowadays and the
      rates of many age-related heart diseases are increasing and this has been
      paralleled by a substantial increase of the rates in the community survey. More
      attention should be paid to these heart diseases in Shanghai and in this century.

PMID- 14728871
TI  - [Assessment of the changes in autonomic nervous function during head up tilt test
      in syncopal patients using spectral analysis of heart rate variability].
AB  - OBJECTIVE: To study the pathological mechanism of vasovagal syncope, spectral
      analysis of heart rate variability was used to evaluate the changes of autonomic
      function during head up tilt test in patients with unexplained syncope. METHODS:
      27 patients with recurrent episodes of unexplained syncope underwent 70 degrees
      head up tilt test. Spectral analysis was used to assess the changes in autonomic
      function before tilt testing, immediately after tilting, just before the
      occurrence of syncope or at the end of the test, during the syncope period or at
      the end of the test and after testing in supine rest. At the same time,
      haemodynamic changes were recorded. Spectral power in very low frequency (VLF,
      0.003 - 0.04 Hz), low frequency (LF, 0.04 - 0.15 Hz) and high frequency (HF, 0.15
      - 2.00 Hz) were computed with Fast Fourier Transform analysis, and LF and HF were
      normalized: LF norm = 100 x LF/(TP-VLF) and HF norm = 100 x HF/(TP-VLF). RESULTS:
      12 patients (mean age 40 +/- 10 years) showed a negative response and 15 patients
      (mean age 37 +/- 9 years) showed a positive response. Both systolic and diastolic
      blood pressure decreased in all the patients [(118.00 +/- 10.42-->81.00 +/-
      12.36) mm Hg, P < 0.01 and (76.00 +/- 8.40-->52.00 +/- 10.95) mm Hg, P < 0.01]
      and heart rate decreased in 8 patients (53%). No significant difference in all
      the indices of spectral analysis was observed in supine position between the
      subjects with positive and negative test results. LF norm in both the groups did
      not alter during the entire tilt procedure. The decreased HF norm and increased
      LF/HF persisted throughout head up tilt test in the negative patients. In the
      positive patients, similar patterns of changes were observed before the
      occurrence of positive symptoms, and during the occurrence of the symptoms. HF
      norm abruptly rose (10.47 +/- 4.04-->32.95 +/- 10.48) and obviously exceeded that
      before tilt testing (23.44 +/- 4.20-->32.95 +/- 10.48, P < 0.05) and LF/HF
      dropped (3.28 +/- 0.39-->1.07 +/- 0.31, P < 0.01). At supine rest just after
      test, all the indices in both groups came back. CONCLUSIONS: In the supine
      position, autonomic function is similar between positive and negative subjects.
      Positive patients have a different pattern of response to the tilting test. The
      pathological mechanism leading to vasovagal syncope appears to be related with
      the abrupt and excessive increase of vagal activity.

PMID- 14728872
TI  - [An experimental study on gastric mucosal damage induced by duodenogastric reflux
      in rats].
AB  - OBJECTIVE: Duodenogastric reflux (DGR) is an important factor causing gastric
      mucosal damage, but whether short-term DGR cause gastric damage and its
      characteristics remain unclear. The aim of the study is to investigate the damage
      of gastric mucosa and its characteristics due to short-term DGR in a rat model.
      METHODS: Healthy, male SD rats were divided into three groups: a DGR group, a
      pylorus ligation group and a control group. The rats were sacrificed three weeks
      after the operation. The damage of gastric mucosa was observed macroscopically
      and microscopically. The pH value and bilirubin level of the gastric fluid were
      examined. The tight junctions between antral mucosal cells were evaluated under
      transmission electronmicroscopy. The serum gastrin concentration was investigated
      with radioimmune assay. Myeloperoxidase (MPO) was examined with chemical method.
      RESULTS: Macroscopically, there were significant mucosal lesions such as
      erosions, ulcers and bleeding spots in the DGR group. Microscopically, short-term
      DGR can cause faveolar hyperplasia, but no apparent intestinal metaplasia and
      atrophy were observed. There was scarcely presence of acute and chronic
      inflammatory cell infiltration and MPO activity remained unchanged. The pH value
      and bilirubin level of gastric fluid increased significantly and the serum
      gastrin concentrations did not change a lot. Short-term DGR can cause destruction
      of tight junction, which was shorter in duration, less in deformation and might
      even disappear at the time of examination. CONCLUSIONS: It is suggested that
      short-term DGR can induce gastric damage, faveolar hyperplasia and tight junction
      destruction without inflammatory cell infiltration and MPO activity changes.

PMID- 14728873
TI  - [The clinical features and prognosis of Aeromonas septicaemia in hepatic
      cirrhosis: a report of 50 cases].
AB  - OBJECTIVE: Aeromonas septicaemia complicating cirrhosis is not a common
      infectious disease. To enhance the knowledge in this aspect, we analysed the
      clinical features, pathogenetic factors, resistance, treatment and prognosis of
      Aeromonas septicaemia in 50 cases of hepatic cirrhosis. METHODS: We cultured the
      bacteria from infected patients with BacT/Alert120 automation instrument made in
      AKsu and identified the bacteria with the Vitek-AMS60 made in Biomerieux company.
      We then tested the susceptibility of Aeromonas to 13 antimicrobial agents.
      RESULTS: A total of 50 cases of Aeromonas septicaemia occurred in severe hepatic
      cirrhosis. The majority of them had severe complications. Aeromonas hydrophila
      was the most common species isolated (52.0%). Nosocomial infection was the
      predominant way of infection. The major clinical manifestations of Aeromonas
      septicaemia were fever (100%), chill (64.0%), abdominal pain (60.0%), diarrhoea
      (32.0%) and shock (24.0%). The susceptive rate of Aeromonas to third generation
      cephalosporin, quinolones and aminoglycoside antibiotics was more than 80%. The
      cure rate and mortality attributed to Aeromonas septicaemia after treating with
      third generation cephalosporin, levofloxacin and their combination were 64.3%,
      75.0%, 57.1% and 28.6%, 12.5%, 35.7% respectively. CONCLUSION: Aeromonas
      septicaemia tends to befall patients with severe hepatic cirrhosis and causes a
      rapidly fatal outcome. Aeromonas should be considered an important pathogen for
      septicemia in patients with liver cirrhosis. It is suggested that we should
      emphasize the clinical features and laboratory diagnosis so as to have proper
      antimicrobial treatment.

PMID- 14728874
TI  - [Susac syndrome: a report of two cases].
AB  - OBJECTIVE: To investigate the clinic characters and diagnosis of Susac syndrome.
      METHODS: Two cases were systematically studied by the authors. RESULTS: All the
      two cases were young women. The clinical manifestations include acute and
      subacute multifocal and diffuse encephalopathic symptoms, hearing loss, and
      visual loss. Diagnosis is facilitated by demonstration of retinal arteriolar
      occlusions without uveitis or keratoconjunctivitis, mid-to-low frequency
      unilateral or bilateral sensorineural hearing loss, and numerous small foci of
      increased signal in the white and gray matter on T2-weighted brain magnetic
      resonance imaging. CONCLUSIONS: This rare syndrome often can be identified at an
      early stage with a careful history and physical examination. MRI, SPECT, retinal
      fluorescein angiography and audiometry will contribute to diagnosis.

PMID- 14728875
TI  - [The effect of peroxisome proliferator-activated receptor alpha and gamma ligands
      on free fatty acid-induced INS-1 cell impairment].
AB  - OBJECTIVE: To investigate the effect of peroxisome proliferator-activated
      receptor alpha and gamma (PPARalpha and PPARgamma) ligands on free fatty acid
      (FFA)-induced pancreatic beta-cell impairment. METHODS: Insulinoma cell line beta
      cell (INS-1 cells) were treated with PPARalpha ligand (clofibrate) and PPARgamma
      ligands (troglitazone and thiazolidinedione). C, N diphenyl-N'-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability assay and
      DNA fragmentation analysis were used to evaluate the effect of PPARalpha and
      PPARgamma ligands on FFA-induced INS-1 cell impairment. RESULTS: The viability of
      INS-1 cells decreased after incubation of the cells with FFA (0.25 - 1 mmol/L)
      for 24 hours. FFA (1 mmol/L) was also found to induce INS-1 cell apoptosis.
      Comparison of the cells treated with or without clofibrate (100 micro mol/L),
      troglitazone (10 micro mol/L) and thiazolidinedione (100 micro mol/L), we found
      that these PPARalpha and PPARgamma ligands could protect INS-1 cells from the
      cytotoxicity of FFA, including lipoapoptosis. CONCLUSION: FFA mediates
      significant lipotoxicity and lipoapoptosis in beta-cells and application of
      PPARalpha and PPARgamma ligands might be of value in protection of beta-cells
      from FFA cytotoxicity.

PMID- 14728877
TI  - [The expression of peripheral blood neutrophil CD64 in systemic lupus
      erythematosus with infection or disease activation].
AB  - OBJECTIVE: To explore the significance of expression of peripheral blood
      neutrophil CD(64) to distinguish infection from disease activation in systemic
      lupus erythematosus (SLE). METHODS: 19 patients with infection and 46 patients
      with non-infection in 65 SLE patients were studied. The levels of peripheral
      blood neutrophil CD(64) were measured by flow cytometry. RESULTS: The levels of
      peripheral blood neutrophil CD(64) in SLE infection patients were [(7.8 +/-
      2.1)%], which were significantly higher than that of non-infection group [(3.2 +/
      1.4)%] and healthy control [(3.0 +/- 1.1)%, P > 0.05]. However, there were no
      significance between the levels of non-infection group and healthy control (P >
      0.05). There were no significance between the levels of CD(64) of disease
      activation and silence group and non-infection group (P > 0.05). In SLE infection
      group, the levels of CD(64) expression in patients with Gram-negative [(9.2 +/-
      1.6)%] were compared with [(7.2 +/- 2.2)%] those with Gram-positive. The
      differences were not significant (P > 0.05). The levels of CD(64) of SLE patients
      with infection were decreased by treatment with antibiotics. The correlation of
      the levels of CD(64) with anti-dsDNA, C(3), ESR, CRP, SLE-disease activity index
      and IFANA were not found (respectively r = 0.104, P = 0.409; r = -0.125, P =
      0.322; r = -0.138, P = 0.274; r = 0.228, P = 0.068; r = 0.204, P = 0.310; r = 
      0.213, P = 0.089). CONCLUSION: The levels of peripheral blood neutrophil CD(64)
      may help us distinguish infection from disease activation in SLE.

PMID- 14728876
TI  - [Anti-mesangial cell autoantibodies and their target antigens in lupus
      nephritis].
AB  - OBJECTIVE: Anti-mesangial cell autoantibodies (anti-MC) have been reported in
      patients with IgA nephropathy and Henoch-Schoenlein purpura. The aim of the
      current study was to identify anti-MC autoantibodies in sera from patients with
      lupus nephritis (LN). METHODS: 96 serum samples were collected from 96 patients
      with renal biopsy proven LN. Anti-MC autoantibodies were examined by cellular
      ELISA and Western blot analysis. In vitro cultured human mesangial cells were
      used as cell substrate in ELISA and the their soluble proteins in non-reducing
      conditions were used as antigens in Western-blot analysis. RESULTS: 37.5% and
      97.9% of the serum samples from patients with LN had anti-MC autoantibodies in
      cellular ELISA and Western blot analysis respectively, and 12 protein bands could
      be blotted by the LN sera in Western blot analysis. The percentage of anti-63 000
      autoantibody positive samples was significant higher in female patients than that
      in the male (59.8% vs 21.4%, P < 0.01). The prevalence of anti-74 000, 46 000,
      and 36 000 autoantibodies were significantly higher in patients with hematuria
      than that in patients without hematuria (36.8% vs 5.0%, P < 0.01; 34.2% vs 10.0%,
      P < 0.05; 31.6% vs 5.0%, P < 0.05; respectively). The prevalence of anti-63 000
      autoantibodies was also significantly higher in patients with ANA than that in
      patients without (67.6% vs 16.7%, P < 0.001). The prevalence of anti-18 000
      autoantibodies was significantly higher in patients with anti-dsDNA antibodies
      than that in patients without (61.5% vs 34.4%, P < 0.05). CONCLUSIONS: There are
      heterogeneous anti-MC autoantibodies in sera from patients with LN. Anti-MC
      autoantibodies may have a pathogenic role in lupus nephritis and some anti-MC
      autoantibodies may be associated with different clinical manifestations.

PMID- 14728878
TI  - [A study on early activation of T lymphocytes and soluble tumor necrosis factor
      receptor in patients with myelodysplastic syndrome].
AB  - OBJECTIVE: To investigate the expression of T cell early activation marker
      (CD(69)) on CD(4)(+) and CD(8)(+) lymphocytes in peripheral blood and the levels
      of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in serum and
      bone marrow in patients with myelodysplastic syndrome (MDS). METHODS: Whole blood
      cell culture procedure was applied to activate T lymphocytes with
      phytohemagglutinin (PHA) (20 mg/L) in vitro. The expression rates of CD(69) on
      CD(4)(+) and CD(8)(+) lymphocytes at 0 h and 4 h after culture were analyzed with
      two-color flow cytometry. The levels of sTNF-R1 and sTNF-R2 in serum and bone
      marrow were measured with ELISA. RESULTS: There was an increase in the expression
      rates of CD(69) on CD(4)(+) and CD(8)(+) cells in RA and RAS patients (8.32% and
      9.88% respectively) and in the expression rate of CD(69) on CD(8)(+) cells in
      RAEB and RAEB-T patients (7.92%) before PHA stimulation. CD(69) expression on
      CD(4)(+) and CD(8)(+) cells were significantly elevated in MDS patients after PHA
      stimulation (53.46% and 51.63% in RA + RAS; 42.93% and 41.96% in RAEB and RAEB-T)
      and the expression rate on CD(4)(+) cells was similar to that on CD(8)(+) cells.
      The levels of the two sTNF-R in MDS patients were elevated. sTNF-R1 in RA and RAS
      (1.58 +/- 0.68) micro g/L (PB), (2.10 +/- 0.26) micro g/L (BM); sTNF-R2 in RA and
      RAS (1.41 +/- 0.50) micro g/L (PB), (1.95 +/- 0.64) micro g/L (BM); sTNF-R1 in
      RAEB and RAEB-T (2.62 +/- 2.55) micro g/L (PB), (3.12 +/- 0.67) micro g/L (BM);
      sTNF-R2 in RAEB and RAEB-T (1.96 +/- 0.56) micro g/L (PB), (3.09 +/- 0.62) micro
      g/L (BM). The levels of sTNF-R2 in serum positively correlated to the expression
      rate of CD(69) on CD(8)(+) cells before PHA stimulation. CONCLUSION: It is
      indicate that the increased early activation and activated potentials of T
      lymphocytes, along with abnormally elevated immunologically active molecules play
      an important role in immune pathogenesis of patients with MDS.

PMID- 14728879
TI  - [Comparison of the characteristics of suicide attempters treated in general
      hospitals with and without prior suicide attempts].
AB  - OBJECTIVE: We compared the characteristics of persons who had made multiple
      versus single suicide attempts to determine whether or not these are two
      independent subgroups and, thus, should be provided with different preventive
      services. METHODS: We administered a 2 - 3 hour interview that included a
      structured psychiatric examination to 325 individuals with suicide attempts who
      were treated at four city and county-level general hospitals. RESULTS: The age,
      gender, years of education, marital status, work status, and family economic
      status of the 52 persons who had made more than one suicide attempt were similar
      to those of the 273 persons who had made a single attempt. But repeaters were
      less likely than non-repeaters to live in rural villages and to attempt suicide
      by ingesting agricultural poisons. Moreover, repeaters considered suicide prior
      to the attempt for a longer time, had a lower quality of life in the prior month,
      had a stronger suicidal intent, had more chronic life events, had a higher
      chronic stress score, and were more likely to have mental illness (P's all <
      0.05). CONCLUSIONS: Major differences in the characteristics of suicide
      attempters with and without a prior history of suicide attempts suggest that
      these are independent subgroups of attempters. These two types of attempted
      suicide require different preventive approaches.

PMID- 14728880
TI  - [Considerations in diagnosis and treatment of glomerular diseases in children-
      opportunities and challenges].

PMID- 14728881
TI  - [One case of congenital lissencephaly].

PMID- 14728882
TI  - [Renal transplantation in children, report of 21 cases].
AB  - OBJECTIVE: The survival rate of cadaveric renal transplant in children has been
      improved following the development of transplantation technology and the
      application of immunosuppressive agents. In this study, the prognosis of renal
      transplantation, operative procedure and immunosuppressive agents administration
      in 21 children with end-stage renal disease (ESRD) were analyzed. METHODS: From
      January 1985 to December 2001, 21 patients (9 males and 12 females with a mean
      age of 14 +/- 2 yr, mean body weight of 33.4 kg and mean height of 136.5 cm)
      received renal transplantation because of ESRD were enrolled in the study. The
      patients with an average GFR of 8.28 ml/min were managed with dialysis for 13.4
      months in average pro-transplantation. All cadaveric kidneys were from adults,
      which included 1 donor with one HLA mismatch, 3 with two mismatches, 5 with three
      mismatches and 4 with four mismatches. All transplantations were performed with
      anastomoses of the adults' renal artery and vein to the children's iliac externa
      artery and iliac externa vein. Biological inducement therapy was given in 4
      cases. At the first 3 - 5 days post-transplantation, methylprednisolone was
      administered [7 mg/(kg.d)]. All patients received baseline diploid or triple
      immunosuppression therapy of cyclosporin A [6 - 8 mg/(kg.d)] or FK506 [0.18 -
      0.25 mg/(kg.d)], mycophenolate mofetil [MMF 10 - 15 mg/(kg.d)] or azathioprine [1
      - 3 mg/(kg.d)] and prednisone [0.4 - 0.6 mg/(kg.d)]. High-dose methylprednisolone
      [10 mg/(kg.d)] was administered to control the acute rejection. RESULTS: The
      renal function of patients was restored 5.6 days in average after
      transplantations. The 1st, 3rd and 5th year survival rates of recipient/graft
      were 95.2%/95.2%, 86.7%/73.3% and 72.7%/63.6%, respectively. One case had super
      acute renal rejection, 5 cases had acute rejection, 3 cases had delayed graft
      function and 3 patients died. The longest survival time was 12 years. The major
      complications included hypertension (47.6%), diabetes (19.4%), infection (19.4%)
      and drug-induced hepatic injury (14.2%). Catch-up growth was seen in most of the
      pediatric recipients. CONCLUSION: Renal transplantation is the most ideal method
      to treat children with ESRD, and the growth of the pediatric patients will be
      improved after transplantation. Adult donor kidneys adapt to the school age
      patient. And the protocol of immunosuppressive therapy (prednisone plus MMF and
      FK506) should be applied.

PMID- 14728883
TI  - [Spleen abscess in a child].

PMID- 14728884
TI  - [A clinico-pathological study comparing Henoch-Schonlein purpura nephritis with
      IgA nephropathy in children].
AB  - OBJECTIVE: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy are very
      similar in immunopathological changes, and therefore some nephrologists
      considered that they are substantially one disease entity caused by IgA immune
      abnormalities, and IgA nephropathy is, in fact, a kind of HSPN without rashes.
      The present study aimed to characterize their relationship through clinico
      pathological comparison between IgA nephropathy and HSPN. METHODS: Thirty-one
      children with IgA nephropathy aged from 3 to 15 years and 120 children with HSPN
      aged between 4 to 15 years were enrolled in this study. Their clinical
      manifestations, blood biochemical test, serum immunology and follow-up data were
      collected and analyzed. Renal pathological findings in light microscopy,
      immunofluorescence and electron microscopy were analyzed and also compared
      between 31 children with IgA nephropathy and 32 children with HSPN. RESULTS: The
      age of onset was over 12 years in 25.8% children with IgA nephropathy, but only
      in 10% with HSPN, and the difference was significant (P < 0.05). The clinical
      patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations
      were seen more often in HSPN, all of them had skin purpura, 59% had
      gastrointestinal symptoms and 47% suffered from arthralgia. While the abdominal
      pain occurred only in 3.2% children with IgA nephropathy. The renal pathological
      investigation showed global sclerosis in 35.5% of IgA nephropathy and 3.1% of
      HSPN, mesangial sclerosis in 41.9% of IgA nephropathy and 6.3% of HSPN, but
      endothelial proliferation in 65.6% of HSPN and 29% of IgA nephropathy. The
      differences were extremely significant (P < 0.01). Thin basement membrane
      nephropathy were only found in 6.5% children with IgA nephropathy, but in none
      with HSPN. The electronic dense deposits in HSPN were sparse, loose and widely
      spread in glomerular mesangium, subendothelial area and even intra basement
      membrane. While the deposits were dense, lumpy and mostly limited in mesangium
      and paramesangium in IgA nephropathy. IgG was found in glomerular immune deposits
      in 71.9% of HSPN, but only 19.4% of IgA nephropathy. No IgG deposit was observed
      in 81.6% of IgA nephropathy, among them most showed IgA and IgM and/or C(3)
      deposit. Predominant IgG deposits were found in 12.5% of HSPN with relatively
      weak IgA deposit, moreover 6.3% of HSPN showed linear IgG deposits in glomerular
      capillary wall, which couldn't be found in IgA nephropathy. The follow-up data of
      average 20 months showed complete remission in 72.5% of HSPN and 19.4% in IgA
      nephropathy after 34 months follow-up. Moreover, 64.5% of IgA nephropathy had
      consistent hematuria and proteinuria, 16.1% had active nephritides, the
      difference was significant (P < 0.05). CONCLUSION: Significant clinico
      pathological differences were found between HSPN and IgA nephropathy, which does
      not support the one disease entity hypothesis. HSPN and IgA nephropathy are
      probably two diseases with similar immune abnormalities.

PMID- 14728885
TI  - [Cyclosporin A treatment of 83 children with nephrotic syndrome of different
      pathological types].
AB  - OBJECTIVE: To evaluate the efficacy of cyclosporin A (CyA) therapy in 83 children
      with nephrotic syndrome of different pathological types. METHODS: Eighty-three
      children enrolled in this study were all hospitalized children with idiopathic
      nephrotic syndrome, aged 3 to 14 yrs (average 8.3 yrs) and included 52 males and
      31 females. There were 35 cases with steroid-dependent, 17 with steroid resistant
      and 26 with frequent relapses. CyA was given to each patient with dosage of 5
      mg/(kg.d) during the corticosteroid was diminished. The renwal biopsy was
      performed in all patients before the administration of CyA. The duration of CyA
      therapy lasted for about 3 to 6 months. The plasma concentration of CyA was
      monitored. RESULTS: Eighty-three children with nephrotic syndrome of different
      pathological types were treated with CyA, including 42 cases of minimal change
      nephrotic syndrome (MCNS), 31 cases of mesangioproliferative glomerulonephritis
      (MsPGN), 5 cases of membranoproliferative glomerulonephritis (MPGN) and 4 cases
      of focal segmental glomerular sclerosis (FSGS). All the 83 patients tolerated
      well to the CyA treatment. Forty-five cases got complete remission, 23 partial
      remission, 15 cases no change after one month treatment with CyA in the hospital.
      The overall response rate was 82%. Patients with different renal pathological
      types showed different responses. Among them, MCNS and MsPGN exhibited the best
      response rates of 86% and 84%, respectively; MPGN cases showed a lower response
      rate and FSGS cases showed the lowest rate. The response time was 7 to 45 days.
      The blood concentration of CyA was monitored for 1 week and 2 weeks after the
      drug was given. The effective drug concentration was maintained at 100 to 200
      microg/L, and the course lasted for 3 to 6 months. During the follow-up of 83
      cases, in 17 of 68 cases the disease relapsed when therapy was tapered or
      discontinued. The relapse rate was 25%. The results indicated that CyA would be
      effective to the relapsed cases. The serum creatinine increased temporarily after
      administration of CyA in 5 cases, N-acetyl-beta-D-glucosaminidase (NAG) in 8
      cases and eventually reached the normal range after the adjustment of dosage. The
      side effects included anorexia, nausea, vomiting and so on. CONCLUSION: CyA is
      one of the effective substitutes for the treatment of nephrotic syndrome,
      especially for the cases with MCNS and MsPGN. And CyA could control refractory
      nephrotic syndrome effectively and rapidly. The clinical effect was related to
      the blood concentration of CyA and pathological types.

PMID- 14728886
TI  - [Renal protective effect of angiotensin II receptor antagonist on growth hormone
      treated nephrotic rats].
AB  - OBJECTIVE: Children with nephrotic syndrome are always associated with
      retardation of growth. Growth hormone (GH) administration to these children can
      stimulate their growth, but it plays an important role in glomerulosclerosis.
      Thus these children would take a risk to use it to improve their growth. This
      study was designed to investigate the effect of GH on the kidney of rats with
      adriamycin-induced nephropathy (AN) and its mechanism, and to observe the
      renoprotective effect of angiotensin II (AngII) receptor antagonist, irbesartan,
      in GH-treated AN rats. METHODS: Rats were divided into the following groups:
      normal control rats, AN rats, GH-treated AN rats and GH plus irbesartan-treated
      AN rats. There were 8 developing male SD rats (120-130 g) in each group. Urinary
      protein was measured at weeks 3, 6 and 9. Blood pressure, serum creatinine, BUN,
      albumin, cholesterol, triglyceride, as well as ACE activity and AngII
      concentration of the kidney were detected at the end of the study. Renal
      pathological changes were evaluated also. Immunohistochemistry was used to
      examine the protein expressions of TGF beta(1), collagen IV and fibronectin in
      glomeruli. RESULTS: Glomerular sclerosis score of GH-treated AN rats (49.4 +/-
      9.8) was significantly higher than that of AN rats (12.8 +/- 5.5, P < 0.01), and
      this score of GH-treated AN rats plus irbesartan (26.2 +/- 7.5) was significantly
      lower than the score of GH-treated AN rats (P < 0.01). The changes of urinary
      protein, hyperlipidemia and hypoalbuminemia in rats of each group consisted with
      the degree of glomerular injury in rats of each group. There was azotemia in GH
      treated AN rats, but rats in the other groups did not have azotemia. ACE activity
      of kidney was significantly (P < 0.01) increased in GH-treated AN rats [(28.1 +/-
      4.1) U/mg pro] and GH-treated AN rats plus irbesartan [(27.6 +/- 3.4) U/mg pro]
      compared with that in AN rats [(14.6 +/- 4.4) U/mg pro]. AngII concentrations in
      the kidney of GH-treated AN rats [(17.8 +/- 3.3) pg/mg pro] and GH-treated AN
      rats plus irbesartan [(27.3 +/- 5.1) pg/mg pro] were significantly higher than
      that in AN rats [(8.3 +/- 1.9) pg/mg pro] (P < 0.01). The protein expressions of
      TGF-beta(1), collagen IV and fibronectin in GH-treated AN rats were the most
      distinct in all groups. These expressions were significantly (P < 0.05) reduced
      in GH-treated AN rats plus irbesartan. CONCLUSION: GH is able to exacerbate
      adriamycin-induced nephropathy in rats, which was partly through activating renal
      tissue RAS and initiating the function of the AngII-TGF beta(1)-ECM axis.
      Angiotensin II receptor antagonist, irbesartan, has some renal protective effects
      on AN rats treated with GH.

PMID- 14728888
TI  - [Interleukin-8 gene expression before and after the pulse treatment with
      methylprednisolone in primary nephrotic syndrome of children].
AB  - OBJECTIVE: Primary nephrotic syndrome (PNS) is one of the common renal diseases
      in children, the pathogenesis of which is unclear. Evidences suggested that the
      proteinuria of NS is associated with the increased expression of the interleukin
      8 (IL-8) genes. The purpose of the study was to evaluate the serum concentration
      and mRNA expression of IL-8 before and after the methylprednisolone pulse therapy
      (MPT) in PNS. METHOD: Thirty children with PNS diagnosed from December 2000 to
      October 2001 were enrolled in this study (patients group). They were not treated
      with glucocorticoid at least within the recent 3 months. The children aged from
      1.5 to 14 years (mean 8.5 years), and included 24 boys and 6 girls. Eighteen
      healthy children were selected as control group after physical examination. The
      children in control group aged from 2 to 14 years (mean 8 years) and included 13
      boys and 5 girls. All patients were treated with MPT intravenously (30 mg/kg) for
      successive 3 days followed by oral prednisone. The serum protein level of IL-8
      was measured by ELISA according to the manufacturer's instructions. Human IL-8
      ELISA kit was purchased from Jingmei corporation Shenzhen, China. And the
      concentration was obtained after drawing the standard curve. The expression of IL
      8 gene was detected with RT-PCR method. The important reverse transcription
      reagent kit and Trizol reagent were all bought from GIBCO BRL, USA. Statistical
      analysis of rank sum test was adopted for data processing. RESULTS: Comparison of
      the serum IL-8 level in the same patient before and after the therapy showed
      significant difference [29.59 (7.14-352.08) ng/L vs. 10.80 (4.27-77.86) ng/L, u =
      4.26, P < 0.01]. The serum level in patient group before the therapy increased
      obviously in comparison to the level of the control group [10.37 (5.46-33.31)
      ng/L, u = 4.53 P < 0.01]. The serum level of IL-8 in patient group after the
      therapy also showed significant difference compared to the control group (u =
      2.73 P < 0.01). The mRNA expression of IL-8 in the same patient before and after
      therapy showed significant difference [0.862 (0.776-0.95) vs. 0 (0-0.754), u =
      3.902 P < 0.01]. CONCLUSION: IL-8 may be involved in the pathogenesis of PNS
      because of the significant increase of the serum IL-8 level and PBMC IL-8 mRNA
      expression in nephrotic syndrome children. Methylprednisolone pulse therapy in
      PNS was able to inhibit the protein production and PBMC mRNA expression of IL-8,
      so the therapeutic mechanism of MPT in PNS might be associated with the
      inhibition of IL-8 expression.

PMID- 14728887
TI  - [Curcumin inhibited the proliferation and extracellular matrix production of
      human mesangial cells].
AB  - OBJECTIVE: Glomerulosclerosis is characterized by extracellular matrix
      accumulative and is often associated with mesangial cell proliferation. Curcumin
      showed a protective effect on anti-glomerular basement membrane (anti-GBM)
      nephritis in vivo, although their cellular localization and mechanism of action
      is still unclear. In this study, a glomerular mesangial cell line derived from
      fetus was used to determine whether curcumin could inhibit the cell proliferation
      and alter the extracellular matrix turnover. METHODS: The cell activity was
      determined with MTT method. Mesangial cells were cultured in vitro and incubated
      with 0, 3.125, 6.25, 12.5, 25, 50, 100 and 200 micromol/L curcumin. In
      addition,human mesangial cells were cultured with or without LPS (10 microg/ml)
      in presence or absence of various concentrations of curcumin (4, 16 and 200
      micromol/L), respectively. The supernatant and cells were collected. Then, the
      levels of the collagen type IV and III protein in the supernatant were determined
      by using enzyme-linked immunosorbent assay and the IL-1 beta and MCP-1 mRNA in
      the cells was measured by semi-quantitative reverse transcription polymerase
      chain reaction (RT-PCR) after subconfluent quiescent mesangial cells were
      incubated with various concentrations of curcumin for 24 h in vitro. RESULTS:
      Curcumin at the concentration equal to or over 6.25 micro mol/L was able to
      inhibit the proliferation of mesangial cells in a dose-dependent manner, the
      optical density according to the sequential concentrations of curcumin was 0.65
      +/- 0.02, 0.62 +/- 0.04, 0.56 +/- 0.01, 0.53 +/- 0.02, 0.51 +/- 0.03, 0.44 +/-
      0.05, 0.41 +/- 0.07 and 0.38 +/- 0.06. Without any stimulation, human mesangial
      cells secreted some collagen type IV and III (10 +/- 9.13 ng/ml and 29.5 +/- 0.58
      ng/ml, respectively) and expressed some MCP-1 mRNA, but did not express IL-1 beta
      mRNA. LPS increased the expression of collagen type IV and III in the culture
      medium of mesangial cells in vitro [(138.75 +/- 23.23) ng/ml and (38.25 +/- 5.38)
      ng/ml] and up-regulated the IL-1 beta and MCP-1 mRNA expression [(16.91 +/-
      1.68)% and (76.6 +/- 6.59)%]. Yet curcumin could significantly decrease collagen
      type IV and III in the supernatant of cultured mesangial cells induced by LPS
      (20.5 +/- 1.00, P < 0.05 and 20.5 +/- 4.12 ng/ml, P < 0.05) and down-regulated
      the mRNA expression of IL-1 beta and MCP-1 in mesangial cells induced by LPS (P <
      0.01). CONCLUSION: Curcumin could inhibit the human mesangial cell proliferation
      and alter the extracellular matrix turnover, meanwhile it could down-regulate the
      IL-1 beta and MCP-1 mRNA expression induced by LPS, which may be valuable in
      decreasing the progression of glomerulosclerosis.

PMID- 14728889
TI  - [Clinical and pathological features of anti-neutrophil cytoplasm antibody
      associated systemic vasculitis in children].
AB  - OBJECTIVE: Anti-neutrophil cytoplasmic antibodies (ANCA) are serological
      diagnostic markers for certain types small vessel vasculitis including Wegener's
      granulomatosis and microscopic polyangiitis, which are also termed ANCA
      associated systemic vasculitis (AASV). The majority of patients with primary AASV
      reported are adults and predominantly elderly. Data on pediatric patients with
      primary AASV in China are lacking. This study aimed to analyze the clinical and
      pathological features of primary AASV in children. METHODS: Patients with primary
      AASV, admitted to the hospital within the past 7 years, were retrospectively
      studied. The clinical and pathological features were compared between pediatric
      and adult patients. In pediatric group, there were 20 cases with an average age
      of (12.1 +/- 4.1) years (aged from 5 to 17 years); in adult group, there were 38
      cases with an average age of (55.3 +/- 14.1) years (aged from 20 to 78 years).
      RESULTS: The data of this study showed that pediatric patients accounted for
      7.87% (20/254) of the whole primary AASV patients. Compared with 38 adult
      hospitalized patients, pediatric patients were predominantly female (80% vs 50%,
      P = 0.047). Patients from both groups were microscopic polyangiitis predominantly
      (95% vs 74%, P > 0.05) and the majority of the sera were P-ANCA/anti-MPO antibody
      positive in both groups (95% vs 74%, P > 0.05). The prevalence of hypertension in
      pediatric patients was significantly lower than that in adults (20% vs 61%, P =
      0.005). There was no significant difference in clinical manifestations and
      clinical remission rates between the two groups. CONCLUSION: Pediatric patients
      with AASV were not rare in China. The clinical and pathological features of
      patients with AASV in childhood were similar to adult patients, but there was a
      female predominance in children.

PMID- 14728890
TI  - [Clinical characteristics of children with enthesitis related arthritis].
AB  - OBJECTIVE: To study clinical characteristics of children with enthesitis related
      arthritis (ERA). METHODS: Twelve patients fulfilling the international league of
      associations for rheumatology (ILAR) criteria for classification of juvenile
      idiopathic arthritis (JIA) and ERA were referred to our department between August
      and November, 2002. Their gender, age, family history, clinical manifestations,
      imaging data, laboratory data and treatment regimens were analyzed
      retrospectively. RESULTS: Of the 12 patients, 11 were male, only one was female;
      their age ranged from 4 to 16 years, and the median age was 10.5 years. Ten (83%)
      of the patients were older than eight years. Among their first degree relatives,
      one had definite ankylosing spondylitis (AS), and 3 presented with a history of
      inflammatory low back pain. Enthesitis occurred in 9. Synovitis occurred in 11,
      most of which were oligoarthritis, predominantly affecting large joints of the
      lower limbs in an asymmetric pattern. Seven patients underwent CT scan, and only
      one had erosions of the sacroiliac joints to achieve a diagnosis of juvenile AS.
      Ten had fever at the onset, and one had a history of diarrhea preceding the
      symptoms of arthritis. Urethritis and balanitis circinata occurred in 3 cases
      fulfilling the classification criteria of Reiter's syndrome, with conjunctivitis
      in 2 and corneitis in one. Elevated inflammatory indicators such as white blood
      cell, neutrophil, platelet, erythrocyte sedimentation rate, C-reactive protein,
      immunoglobulins and serum complement C3 were common during the acute illness.
      Mild anemia was found in 4, and reactive hemophagocytosis in 4 bone marrow
      specimens. DNA of human parvovirus B19 was detected in sera of 2 cases. One had
      positive IgM antibody to coxsackie virus B. All 12 cases were rheumatoid factor
      negative and HLA-B27 positive. Nonsteroidal anti-inflammatory drugs and
      sulfasalazine were the mainstay of treatment. Corticosteroids were added in 3
      cases as a "bridge" therapy due to the severe systemic inflammation. Methotrexate
      was used in 4 cases with refractory disease or with the hip involved, and in 2 of
      them cyclophosphamide was added. CONCLUSION: The clinical characteristics of ERA
      can facilitate an early diagnosis so as to avoid joint damage and disabilities.

PMID- 14728891
TI  - [Clinical feature of four cases with bronchiolitis obliterans].
AB  - OBJECTIVE: To recognize the clinical features of the bronchiolitis obliterans.
      METHOD: Clinical manifestation, chest X-ray, computed tomography (CT) and
      pulmonary function of 4 cases with bronchiolitis obliterans were retrospectively
      analyzed. RESULT: Two cases were after Stevens-Johnson syndrome (SJS), the other
      2 were after severe pneumonia, including one suffered from adenovirus pneumonia.
      Cough, tachypnea and wheezing persisted in all the 4 patients. The symptoms
      lasted for at least 6 weeks, in one case for over one year. Crackles and wheezing
      were present in all the 4 cases. Hyperinflation was seen in chest radiographs in
      all cases. On pulmonary CT/high-resolution CT (HRCT), patchy opacity and
      bronchial wall thickening were seen in each patient. Areas of air trapping were
      seen in three cases. Bronchiectasis was seen in 2 cases, atelectasis and mosaic
      perfusion were seen respectively in one case. PO(2) was low in all the four
      cases. Wheezing was not responsive to beta(2) agonist and other bronchodilating
      therapy. Prednisone was used at a dose of 1 mg/(kg.d) in 3 cases. Two cases were
      followed up for 3 months. The clinical condition of one case was improved, whose
      wheezing and bronchiolar constriction disappeared, cough and dyspnea were also
      relieved. However, the condition of one patient was not improved, although the
      wheezing disappeared. The HRCT of these two cases showed no improvement.
      CONCLUSION: Clinical symptoms of BO were cough, tachypnea, and wheezing after
      acute lung injury. Crackles and wheezing were the most common signs in the BO.
      Chest radiographs showed hyperinflation. Pulmonary CT showed bronchial wall
      thickening, bronchiectasis, atelectasis, and mosaic perfusion. Pulmonary function
      tests suggested obstruction of small airway.

PMID- 14728892
TI  - [Genotype of human calicivirus from infants with diarrhea in Guangzhou city in
      2001].
AB  - OBJECTIVE: To understand the characteristics of human calicivirus (HuCV)
      infection in infants with diarrhea in Guangzhou city and to study genotype of the
      virus. METHODS: The authors collected fecal specimens from 22 children with acute
      nonbacterial gastroenteritis from November to December, 2001. HuCV was detected
      from the specimens by RT-PCR. The PCR products were cloned into the PMD18-T
      cloning vector and sequenced. RESULTS: HCV was detected from the specimens of 2
      cases (9%, 2/22). The nucleotide sequence analysis revealed that the virus
      strains belonged to genotype 2 of Norwalk-like viruses. CONCLUSION: HuCV is one
      of the pathogens causing diarrhea in infants and young children in Guangzhou
      area. HuCV infection occurred sporadically in autumn and winter.

PMID- 14728893
TI  - [HBV C gene mutation in the transmission from father to infant].
AB  - OBJECTIVE: Hepatitis B virus (HBV) DNA was detected from infants whose mothers
      were negative for all HBV markers and the fathers were HBV carrier, the homology
      of HBV sequence of fathers and fetus was high, and HBV mutations concentrated on
      some points, and the transmission of HBV from father to fetus was also identified
      in some reports. The present study aimed to study HBV transmission from father to
      infant. METHODS: The study enrolled 16 pairs of fathers who were HBV carriers and
      infants whose mothers were negative for HBV markers. The infants had evidences
      for intrauterine HBV infection. The five HBV serum markers HBsAg, HBeAg, anti
      HBe, anti-HBs, and anti-HBc were detected with ELISA. The positive results for
      HBsAg and/or HBeAg were regarded as markers of HBV infection. Amplification of
      HBV DNA was done using a nested PCR method. The first amplification was carried
      out using primer C1 (nt 2394-2370), and primer C3 (nt 1730-1754). The second
      amplification was carried out using primer C2 (nt 1955-1974) and primer C6 (nt
      2348-2330). Both primers were designed to amplify the part of sequence coding for
      the hepatitis B C antigen. The size of the amplified fragment obtained by the
      nested PCR was expected to be 394 bp. The PCR products were electrophoresed on
      1.5% agarose gels, which were then stained with ethidium bromide and observed
      with ultraviolet transillumination. When 394 bp specific band was detectable, the
      sample was designated positive. Then the positive samples were identified by dot
      blot. The second PCR products were extracted by phenol-chloroform and 70% ethanol
      precipitation, then resuspended in TE buffer (pH8.0), and used as the template
      for cloning. The template was connected into pGEM-T vector by ligase. The ligated
      products were cloned into fresh competent JM109 cells, and incubated for 90
      minutes at 37 degrees C on roller drum. Finally several dilutions were plated on
      plates containing ampicillin, X-Gal and IPTG, and incubated at 37 degrees C
      overnight. The white colony on plates was used for identification by the nested
      PCR with the above primers. When the 394 bp band was detectable by
      electrophoresis of PCR products in 1.5% agarose gels, the colony was designated
      positive; a positive colony was incubated in LB medium for 8 to 12 hrs, then
      plasmid was extracted using the Wizard Plus SV Minipreps DNA Purification System
      Kit (Promega). The purified plasmid was sent to Beijing Saibaisheng Company for
      sequencing. The homology of HBV C nt 2022-2301 sequence was compared between
      fathers and infants. RESULTS: The homology of HBV C nt 2022-2301 sequence were
      99% - 100% in 16 pairs of fathers and infants. The results were referred to the
      published sequence of HBV adw/adr clones, and the nucleic acid databases were
      searched for homology by using BLAST tool on Internet. HBV of the sixteen pairs
      of father/infant was closely related to the Japan strain (Genebank accession
      number AF121249), but there were still 17 more mutations at nucleotide positions
      2029, 2034, 2044, 2059, 2078, 2095, 2104, 2154, 2161, 2169, 2189, 2201, 2233,
      2251, 2284, 2288, 2293. Moreover the mutations at positions 2189, 2288 resulted
      in the substitution of the encoded amino acid (corresponding to amino acid
      positions 97 and 130, respectively), the other mutations at the position were
      nonphenotypic. The mutation of 2189, 2288 nucleotide of HBV C gene caused 97, 130
      amino acid substitution for isoleucine to leucine and proline to threonine. The
      mutation of 2189, 2288 nucleotide of HBV C gene were detected in 6 (37.5%) of 16
      pairs of fathers and infants. CONCLUSION: The HBV transmission from father to
      infants did exist. The main HBV C gene mutation strains also existed in the
      transmission.

PMID- 14728894
TI  - [Histopathological changes of duodenal salami ulcer in children].
AB  - OBJECTIVE: Duodenal salami ulcer is a common disease found on routine endoscopic
      examination in children. The purpose of the study was to explore the
      characteristics and the clinicopathological features of duodenal salami ulcer in
      children and to deepen the understanding of duodenal salami ulcer. METHODS: The
      endoscopic results of 117 cases with the duodenal salami ulcer were analyzed. The
      specimens of gastric antrum and duodenal bulb were subjected to HE and Giemsa
      staining and were examined for any alteration in histopathology and infection
      with Helicobacter pylori (Hp). The duodenal mucosa was stained with AB (pH
      2.5)/PAS in order to diagnose the duodenal metaplasia. RESULTS: The major
      endoscopic finding was a kind of hoarfrost, which was dotty or flaky, covered on
      the hyperemic and edematous mucosa. The detection rate of this change was 2.29%
      (117/5 106) of all the endoscopic examinations in children and the rate among
      cases with duodenal ulcer was 49.2% (117/238). The histopathology was
      characterized by a heavy infiltration of mainly lymphocytes, plasmocytes and
      neutrophilic granulocytes, frequently accompanied by superficial erosion. Sixty
      one cases were pathologically diagnosed as chronic active duodenitis, superficial
      erosion in 45; chronic duodenitis in 50; eosinophilic duodenitis in 6. Detection
      rate of Hp in gastric antrum was 58% (68/117) of all cases. Detection rate of Hp
      infection and gastric epithelium metaplasia in duodenal bulb was 11.1% (13/117)
      and 31.1% (37/117), respectively. However, detection rate of Hp in gastric antrum
      was 25.0% (1 203/4 810) in 4 810 cases of normal duodenal bulb and chronic
      duodenitis in the same period. Detection rate of Hp in duodenal bulb was 0% and
      the detection rate of gastric epithelium metaplasia in duodenal bulb was 2.7%
      (128/4 810). All these detection rates were much higher than those of the
      specimens collected during the same period with normal duodenal bulb and chronic
      duodenitis (P < 0.001). Twenty-one cases were reexamined by endoscopy after
      having been treated with antacids or antacids and antimicrobial agents for 4
      weeks. The lesions were healed up and no scars were found. CONCLUSION: Duodenal
      salami ulcer in children had a special manifestation of duodenal inflammation or
      erosion but not a real ulcer. It was caused by the Hp infection in gastric antrum
      or duodenal bulb and the increase of gastric acids. The therapeutic principles
      were antacid and antimicrobial agents. The prognosis was good.

PMID- 14728895
TI  - [Changes in variants of attention during a follow-up study of attention deficit
      hyperactivity disorder treated with cerebro-electric feedback].

PMID- 14728896
TI  - [Outcome and prognosis of children with vesicoureteral reflux].

PMID- 14728897
TI  - [Screening of genes involved in renal interstitial fibrosis in rats with
      unilateral ureteral obstruction].

PMID- 14728898
TI  - [Responses of gamma-interferon and interleukin-4 in children with juvenile
      rheumatoid arthritis].

PMID- 14728899
TI  - [Preventive effect of canthardin against hypoxic damage in renal tubular
      epithelial cells].

PMID- 14728900
TI  - [Effects of external bifidobacteria on intestinal microflora and liver function
      in newborn rabbits with parental nutrition].

PMID- 14728902
TI  - [Familial IgA nephropathy].

PMID- 14728901
TI  - [Report of a case with vitamin D dependent rickets].

PMID- 14728903
TI  - [Progresses in clinical application of anti-arrhythmic drugs (II)].

PMID- 14728904
TI  - [Relationship of glucocorticoid receptor gene variations and glucocorticoid
      resistance].

PMID- 14728905
TI  - [Anti-inflammatory action of alpha-melanocyte-stimulating hormone].

PMID- 14728906
TI  - [Prevention of unintentional child injuries].

PMID- 14728907
TI  - Death in the heat: can football heat stroke be prevented?

PMID- 14728908
TI  - Heading in soccer: is it safe?
AB  - Soccer is the world's game, played by 120 million people around the world and 16
      million in the United States. It is unique in that it forbids the use of the
      upper extremity, other than by the goalkeeper or when throwing the ball into play
      from the sideline. It is also unique in that it is the only sport in which the
      head is purposefully used to strike the ball. As sports medicine has evolved, so
      has our curiosity about how certain sport-specific skills or protective equipment
      might change the injury profile of a sport. For soccer, there has been some
      concern that heading may be associated with the development of cumulative
      traumatic brain encephalopathy, or the "punch drunk" syndrome described in
      boxers. This article discusses this question in detail, with a critical look at
      the literature and an emphasis on the prospective data.

PMID- 14728909
TI  - Epilepsy and sports participation.
AB  - Epilepsy is a common disease found in 2% of the population, affecting both young
      and old. Unfortunately, epileptics have previously been discouraged from
      participation in physical activity and sports for fear of inducing seizures or
      increasing seizure frequency. Despite a shift in medical recommendations toward
      encouraging rather than restricting participation, the stigma remains and
      epileptics continue to be less active than the general population. This results
      in increased body mass index, decreased aerobic endurance, poorer self-esteem,
      and higher levels of anxiety and depression. Although there are rare cases of
      exercise-induced seizures, studies have shown that physical activity can decrease
      seizure frequency, as well as lead to improved cardiovascular and psychologic
      health. The majority of sports are safe for epileptics to participate in with
      special attention to adequate seizure control, close monitoring of medications,
      and preparation of family, coaches, or trainers. Contact sports including
      football, hockey, and soccer have not been shown to induce seizures, and
      epileptics should not be precluded from participation. Water sports and swimming
      are felt to be safe if seizures are well controlled and direct supervision is
      present. Additional care must be taken in sports involving heights such as
      gymnastics, harnessed rock climbing, or horseback riding. Sports such as hang
      gliding, scuba diving, or free climbing are not recommended, given the risk of
      severe injury or death, if a seizure were to occur during the activity. This
      article reviews the risks and benefits of physical activity in epileptics,
      discusses sports in which epileptics may participate, and addresses how to
      decrease possible risks for injury.

PMID- 14728910
TI  - The role of the helmet in the prevention of traumatic brain injuries.
AB  - Today, traumatic brain injuries (TBIs) exceed 1 million cases per year. Tens of
      thousands of people die and hundreds of thousands of people are hospitalized. The
      health care costs exceed US dollars 50 billion. The Centers for Disease Control
      and Prevention estimate that people with mild TBIs who are not hospitalized add
      another US dollars 17 billion to the total dollars spent on care. These high
      frequencies and costs place a high priority on programs and procedures to
      minimize the number of injuries and to reduce the severity of those that occur.
      One of these programs focuses on the protective devices worn by the people that
      work and play in environments where there is an identified risk of TBI. Because
      these environments cover a wide variety of activities, the design and
      effectiveness of these protective devices must be specific to the nature of the
      activity and the person they are designed to protect.

PMID- 14728911
TI  - Maxillofacial injuries in sport.
AB  - Maxillofacial injuries occur in contact and noncontact sports. Despite
      advancements in protective equipment and rule changes, there is still an
      unacceptably high rate of maxillofacial injuries. These injuries are clinically
      challenging. The significant morbidity, deformity, and disability associated with
      these injuries can be avoided by their prompt diagnosis and appropriate
      management. It is important for the sports medicine professional to be competent
      in the correct diagnosis and management of maxillofacial injuries. This article
      reviews some of the major maxillofacial injuries, along with their emergent
      examinations and treatments.

PMID- 14728912
TI  - Rehabilitation of the athlete with low back pain.
AB  - The rehabilitation of athletes with low back pain should be considered an
      essential component of their care. Comprehensive rehabilitation begins at the
      time of acute injury and encompasses the period of acute care through sport
      specific training and return to competition. Rehabilitation of athletes with
      spinal pain should include a thorough psychosocial evaluation to identify
      potential barriers to clinical improvement. For athletes with low back pain,
      establishing effective core stability is central to optimizing the functional
      performance of the athlete.

PMID- 14728913
TI  - Etiology of low back pain in athletes.
AB  - Low back pain and injury is a common affliction for patients involved in athletic
      endeavors. For this reason, the health care professional should be cognizant of
      age-related and sports-specific considerations when evaluating athletes with low
      back complaints. An elevated index of suspicion with regard to specific
      etiologies of back pain proves invaluable in order to avoid the misdiagnosis of a
      more serious problem. Although a number of conditions exist that require more
      aggressive evaluation and treatment, the majority of low back pain in athletes is
      self-limiting. In this context, a treatment plan designed to increase low back
      and abdominal muscle strength, flexibility, and range of motion often proves
      beneficial not only in returning the athlete to competition, but also in
      preventing injury recurrence.

PMID- 14728914
TI  - Thoracic hyperkyphosis in the young athlete: a review of the biomechanical
      issues.
AB  - Can intense athletic training cause progression of a thoracic hyperkyphosis in
      the immature athlete? The lack of prospective, controlled trials addressing this
      issue precludes a definitive answer. Hyperkyphosis is defined radiographically as
      a thoracic kyphosis exceeding 55 masculine in 10- to 20-year-olds, and 65
      masculine using back surface measurements. In this paper we review the
      biomechanical scenarios that could lead to an increase in kyphosis in the
      immature athlete via excessive mechanical loading. These include fall-related
      impacts, rapid acceleration/deceleration of heavy weights, and maximum effort
      trunk extensor muscle lengthening contractions. Research is needed on whether the
      number and magnitude of vertebral loading cycles, the recovery interval between
      loading cycles, and the frequency of training affect apophyseal growth during
      periods of rapid growth of the apical vertebrae in a hyperkyphotic spine.

PMID- 14728915
TI  - Thoracic region pain in athletes.
AB  - Pain in the thoracic region in athletes is more commonly from the thorax than
      from the thoracic spine. Although the thoracic spine is well protected from
      motion by the ribs, the chest wall and surrounding muscles are vulnerable to both
      overuse and acute injury in athletes. These injuries to muscle and bone include
      stress fractures, muscle strains, and avulsions. They are diagnosed primarily by
      history and physical examination. Bone scan is the most useful test if there is a
      question of a stress fracture. Most of these injuries respond to conservative
      treatment.

PMID- 14728916
TI  - Interhemispheric visuo-motor integration in humans: the role of the superior
      parietal cortex.
AB  - We used event-related functional magnetic resonance imaging (fMRI) to investigate
      the neural correlates of basic interhemispheric visuo-motor integration. In a
      simple reaction time task, subjects responded to lateralized left and right light
      flashes with unimanual left and right hand responses. Typically, reaction times
      are faster for uncrossed responses (that is, visual stimulus and response hand on
      the same side) than for crossed responses (that is, visual stimulus and response
      hand on opposite sides). The chronometric difference between crossed and
      uncrossed responses is called crossed-uncrossed difference (CUD) and it is
      typically taken to represent a behavioral estimate of interhemispheric transfer
      time. The fMRI results obtained in normal right-handers show that the crossed
      conditions yielded greater activity, compared to the uncrossed conditions, in
      bilateral prefrontal, bilateral dorsal premotor, and right superior parietal
      areas. These results suggest that multiple transfers between the hemispheres
      occur in parallel at the functional levels of sensory-motor integration
      (posterior parietal), decision-making (prefrontal) and preparation of motor
      response (premotor). To test the behavioral significance of these multiple
      transfers, we correlated the individual CUDs with the difference in signal
      intensity between crossed and uncrossed responses in the prefrontal, dorsal
      premotor, and right superior parietal activated areas. The analyses demonstrated
      a strong correlation between the CUD and signal intensity difference between
      crossed and uncrossed responses in the right superior parietal cortex. These data
      suggest a critical role of the superior parietal cortex in interhemispheric visuo
      motor integration.

PMID- 14728917
TI  - Recognition memory for single items and for associations in amnesic patients.
AB  - Recognition memory performance reflects two distinct processes or types of memory
      referred to as recollection and familiarity. According to theoretical claims
      about the two types of memory, single item and associative recognition tasks can
      be used as an experimental method to distinguish recollection and familiarity
      processes. Associative recognition decisions can be used as an index of
      recollection while memory for single items is mostly based on familiarity
      judgement. We employed this procedure to examine a possible dissociation in the
      memory performance of amnesic patients between spared single item and impaired
      associative recognition. Twelve amnesic patients, six with damage confined to the
      hippocampus proper, and six with damage elsewhere in the brain, were recruited
      for the present study. The findings showed that hippocampal amnesics exhibit
      relative sparing of single item learning but are consistently deficient in the
      learning of all kinds of between-item associations. These results are consistent
      with the view that hippocampal formation contributes differently to declarative
      tasks that require recollective or familiarity processes.

PMID- 14728918
TI  - Functional reorganisation in patients with right hemisphere stroke after training
      of alertness: a longitudinal PET and fMRI study in eight cases.
AB  - In patients with alertness deficits due to right hemispheric vascular brain
      damage, training induced changes in the individual functional networks involved
      in intrinsic alertness were assessed in a longitudinal positron emission
      tomography (PET)/fMRI activation study. Patients were trained by administering
      the alertness routine of the AIXTENT computerized attention training or, in the
      control condition, by using a computerized training of verbal and topological
      memory. Before and after the training, both a PET/fMRI and a neuropsychological
      assessment were carried out. In this paper, we are presenting four patients after
      alertness training: three, whose alertness performance improved significantly
      after training, and one, who did not improve. In the patients showing behavioural
      improvement, the PET/fMRI activation after training revealed partial restitution
      of the right hemisphere (RH) functional network known to subserve intrinsic
      alertness in normal subjects, especially in the right dorsolateral or medial
      frontal cortex. For the patient without behavioural improvement, the PET
      activation after training showed an increase of activation only in the left
      hemisphere. Out of the four patients in the memory training control group only
      one showed significant improvement of alertness. Another patient had an increase
      of right frontal activation after the training but this did not correspond to
      behavioural improvement. In a control group of six normal participants,
      repetition of the alertness activation paradigm in fMRI revealed a decrease of
      right frontal and parietal activation from the first to a second measurement
      after 3 weeks, in contrast to the observed training induced effects in the
      patients.

PMID- 14728919
TI  - The impact of change in stimulus format on the electrophysiological indices of
      recognition.
AB  - The present study investigated the impact of changes in stimulus format between
      study and test on the event-related potential (ERP) correlates of recognition. To
      this end subjects studied the names and pictures of common objects. At retrieval,
      subjects were presented with old items for which the presentational format had
      changed (from picture to name or vice versa), old items that were shown in the
      same format as at study, and new items. ERPs revealed three temporally, spatially
      and functionally dissociable memory-related effects: an early bilateral frontal
      effect, which was sensitive to the perceptual similarity between study and test
      stimulus; a left temporo-parietal effect, which was sensitive to the type of
      stimulus that was encoded; and a late frontal effect, which was largest over
      right electrode sites and appeared to be sensitive to the type of test stimulus.
      The results provide further evidence for a functional dissociation between the
      early bilateral frontal and the later temporo-parietal old/new effect, suggesting
      an interpretation in terms of processes contributing to a perceptually-driven
      familiarity or novelty assessment and recollection, respectively.

PMID- 14728920
TI  - Do high functioning persons with autism present superior spatial abilities?
AB  - This series of experiments was aimed at assessing spatial abilities in high
      functioning individuals with autism (HFA), using a human-size labyrinth. In the
      context of recent findings that the performance of individuals with HFA was
      superior to typically developing individuals in several non-social cognitive
      operations, it was expected that the HFA group would outperform a typically
      developing comparison group matched on full-scale IQ. Results showed that
      individuals with autism performed all spatial tasks at a level at least
      equivalent to the typically developing comparison group. No differences between
      groups were found in route and survey tasks. Superior performance for individuals
      with HFA was found in tasks involving maps, in the form of superior accuracy in
      graphic cued recall of a path, and shorter learning times in a map learning task.
      We propose that a superior ability to detect [Human Perception and Performance 27
      (3) (2001) 719], match [Journal of Child Psychology and Psychiatry 34 (1993)
      1351] and reproduce [Journal of Child Psychology and Psychiatry 40 (5) (1999)
      743] simple visual elements yields superior performance in tasks relying on the
      detection and graphic reproduction of the visual elements composing a map.
      Enhanced discrimination, detection, and memory for visually simple patterns in
      autism may account for the superior performance of persons with autism on visuo
      spatial tasks that heavily involve pattern recognition, either in the form of
      recognizing and memorizing landmarks or in detecting the similarity between map
      and landscape features. At a neuro-anatomical level, these findings suggest an
      intact dorso-lateral pathway, and enhanced performance in non social tasks
      relying on the infero-temporal pathway.

PMID- 14728921
TI  - Deficient arithmetic fact retrieval--storage or access problem? A case study.
AB  - This paper aims at clarifying the nature of fact retrieval difficulties in an 18
      year-old young man (MO) who exhibited a puzzling pattern of developmental
      dyscalculia. Contrasting performance on explicit (production and verification
      tasks) and implicit (priming) tasks we observed poor overt retrieval of addition
      and multiplication facts, classical interference effects in verification tasks
      and inconsistency of error patterns. Hence, MO's performance pattern is
      suggestive of the existence of a partly stored network of facts (reflecting
      imperfect storage), but is also compatible with an access deficit according to
      Warrington and Cipolotti's [Brain 119 (1996) 611] criteria for distinguishing
      access and storage deficits in dysphasic patients. Furthermore, while MO
      displayed interference effects in verification tasks, he did not show automatic
      access to arithmetic facts in implicit tasks. Finally, similar to the findings of
      Roussel, Fayol, and Barrouillet [European Journal of Cognitive Psychology 14(1)
      (2002) 61] on normal subjects, MO's performance pattern is suggestive of the
      existence of differential processing mechanisms for addition and multiplication
      facts. We propose a unifying mechanism, namely a deficit of the central executive
      of working memory (WM), that accounts both for the constitution of a fuzzy
      network of fact representations, and for an access deficit modulated by
      attentional demands as required in explicit/implicit task paradigms. Overall, our
      results clearly provide evidence that even in (a developmental) case of a non
      perfect network of memory representations (e.g. [Journal of Experimental
      Psychology: General 117 (1988) 258]), interference effects might be observed.
      Future studies thus need to be cautious before concluding that interference
      effects prove the existence of a well-established associative memory network of
      arithmetic facts.

PMID- 14728922
TI  - Processing and short-term retention of relational information in amnesia.
AB  - In a recent eye-movement study [Psychol. Sci. 11 (2000) 454], amnesic patients
      failed selectively to exhibit long-term effects of memory for the relations among
      the constituent elements of scenes. This failure could be due to a deficit
      specifically in long-term relational memory, as we have suggested; or in
      retention of relational information over any delay, whether involving perceptual
      processing and short-term maintenance or long-term memory, consistent with
      suggestions from recent studies of the hippocampus; or in on-line processing of
      relational information, as would occur in perceptual or feature binding. Here we
      show robust eye-movement effects of relations among elements of scenes in amnesia
      in a short-delay matching task, with the same materials and in the same amnesic
      patients in which long-delay conditions elicited failure. These findings document
      intact processing and short-term retention of relational information in amnesia,
      indicating that amnesia associated with hippocampal damage results in a
      relational memory deficit, specifically of long-term memory.

PMID- 14728923
TI  - Neural processing of nouns and verbs: the role of inflectional morphology.
AB  - Dissociations of nouns and verbs following brain damage have been interpreted as
      evidence for distinct neural substrates underlying different aspects of the
      language system. Some neuroimaging studies have supported this claim by finding
      neural differentiation for nouns and verbs [Brain 122 (1999) 2337] while others
      have argued against neural specialisation [Brain 119 (1996) 159; Brain 124 (2001)
      1619]. We suggest that one reason why these inconsistencies may have arisen is
      because the morphological structure of nouns and verbs has been ignored. In an
      event-related functional magnetic resonance imaging (fMRI) study we test the
      hypothesis that the neural processing of nouns and verbs differs when they are
      inflected. We contrasted the processing of regularly inflected nouns (dogs) with
      regularly inflected verbs (hitting), and found that the LIFG was more strongly
      activated in processing regularly inflected verbs compared to regularly inflected
      nouns. Moreover, regions of LIFG that were more active in the fMRI study for
      inflected verbs partially overlapped with the lesions in patients who have
      particular problems with verb morphology. Taken together with previous studies,
      these results suggest that noun and verb stems do not differ in terms of their
      representation, but when verbs are morphologically complex they differentially
      engage those neural systems which are involved in processes of morpho-phonology
      and syntax.

PMID- 14728924
TI  - Impaired probabilistic category learning in hypoxic subjects with hippocampal
      damage.
AB  - Previous research has suggested that a probabilistic category learning task (e.g.
      weather prediction task) can be used to elucidate brain substrates of learning.
      We tested amnesic subjects with bilateral hippocampal damage due to hypoxia and
      matched controls on the weather prediction task and a variant, the "ice cream"
      task, which maintains a similar category structure. The hypoxic subjects were
      impaired relative to controls on both tasks; in the ice cream task, this
      difference was evident even early in training (first 50 trials). This finding is
      similar to functional neuroimaging (fMRI) studies in healthy subjects, which show
      medial temporal involvement even in early learning on this task. Additionally,
      strategy analysis of response patterns during learning suggest that the hypoxic
      group relied more heavily on simple, degraded learning strategies than did the
      control group. These results may suggest a qualification of the generally held
      conclusion that amnesic patients are not impaired at probabilistic category
      learning: at least under some circumstances, amnesic patients show an early and
      lasting deficit.

PMID- 14728925
TI  - Long-term neuropsychological deficits after cerebellar infarctions in two young
      adult twins.
AB  - Two young adult dizygotic twins with high schooling suffered two strokes at the
      ages of 26 and 30 years. On the first occasion, Case 2 suffered a stroke only a
      few months after Case 1; on the second occasion, Case 1 suffered a second stroke
      a few months after Case 2. In Case 1, lesions were mainly localized to the left
      cerebellar hemisphere in both stroke episodes. Case 2 suffered lesions localized
      to the right cerebellar hemisphere in the first stroke episode, and multiple
      lesions in both cerebellar hemispheres and the vermis, right pons and left
      thalamus during the second stroke episode. Seven years after the second stroke,
      despite full recovery of motor functions, the patients still show mild, yet
      selective, linguistic deficits (syntactic comprehension deficits, mild
      agrammatism, reading and writing disorders) without speech disturbances. They
      also present with selective dysfunctions in visuospatial short-term memory.
      Language disorders are ascribed to a dysfunction of the cerebellum in Case 1,
      while in Case 2 a dysfunction of the cerebellum and the thalamus is considered as
      both structures are part of the so-called 'frontal lobe system', which supports
      language generation. Visuospatial short-term memory disorders are attributed to
      an impaired ability to appreciate the organizing structure of the visual task and
      to poor planning strategies, which are in turn ascribed to cerebellar lesions.
      The role of the cerebellum in cognitive and linguistic functions is discussed.

PMID- 14728926
TI  - Lack of false recognition in schizophrenia: a consequence of poor memory?
AB  - The tendency to falsely recognize items as ones previously presented is increased
      in patients with frontal lesions and in older participants, whereas patients with
      medial temporal lobe damage may display such poor memory that they are not
      especially susceptible to false recognition. Since patients with schizophrenia
      are often compared to these groups neurocognitively, we explored the extent to
      which they are more susceptible to false memory. Participants were presented with
      word lists along a semantic theme, such as "bread". After list presentation,
      recognition tasks were administered which contained both the studied words as
      well as unstudied words. Some of the unstudied words were related to the theme of
      the previously studied words, but never actually presented (e.g. semantic
      "lures"). In a separate test, free recall of these lists of words was assessed.
      Interestingly, it was control participants who made more errors at recall, and
      were especially susceptible to intrusions of the semantic lures. Patients with
      schizophrenia did not make more false recognition errors in general, and
      surprisingly they made disproportionately fewer false recognition errors to
      semantic lures specifically. We conclude that despite poor memory, patients with
      schizophrenia are not especially susceptible to interference from previous tasks
      and are not particularly prone to false recollections.

PMID- 14728927
TI  - Sex differences in mental rotation and spatial rotation in a virtual environment.
AB  - The visuospatial ability referred to as mental rotation has been shown to produce
      one of the largest and most consistent sex differences, in favor of males, in the
      cognitive literature. The current study utilizes both a paper-and-pencil version
      of the mental rotations test (MRT) and a virtual environment for investigating
      rotational ability among 44 adult subjects. Results replicate sex differences
      traditionally seen on paper-and-pencil measures, while no sex effects were
      observed in the virtual environment. These findings are discussed in terms of
      task demands and motor involvement. Sex differences were also seen in the
      patterns of correlations between rotation tasks and other neuropsychological
      measures. Current results suggest men may rely more on left hemisphere processing
      than women when engaged in rotational tasks.

PMID- 14728928
TI  - The future of clinical cancer research: who's teaching the next generation? The
      Flims-Vail model.

PMID- 14728929
TI  - Preoperative ultrasound-guided node biopsy and sentinel node augmented node
      sample is best practice.

PMID- 14728930
TI  - Implications of lymphatic mapping for staging and adjuvant treatment of patients
      with breast cancer.
AB  - Lymphatic mapping has become a frequently used technique for staging the axilla
      in patients with breast cancer. In addition to sentinel nodes in the axilla,
      lymphoscintigraphy depicts sentinel nodes outside the axilla in up to 34% of
      patients. An increasing number of surgeons are now pursuing these extra-axillary
      nodes and are able to harvest them with limited morbidity in up to 87% of the
      patients concerned. Improved accuracy of staging is the result. Surgeons,
      radiotherapists and medical oncologists should consider the implications of the
      presence or absence of metastatic disease in such nodes. Incorporating the tumour
      status of these extra-axillary sentinel nodes in the management of patients will
      lead to a better selection of those who may benefit from postoperative
      radiotherapy to the internal mammary lymph node chain and from adjuvant systemic
      treatment.

PMID- 14728931
TI  - Sentinel node procedure in breast carcinoma: a valid tool to omit unnecessary
      axillary treatment or even more?

PMID- 14728932
TI  - Methodological issues in assessing health-related quality of life of colorectal
      cancer patients in randomised controlled trials.
AB  - Although health-related quality of life (HRQOL) is increasingly reported as an
      important endpoint in cancer clinical trials, questions still remain about the
      quality of its reporting. The aim of this study was to evaluate the level of
      reporting of HRQOL in randomised controlled trials (RCTs) of colorectal cancer
      (CRC). A systematic literature search from 1980 to March 2003 was undertaken on a
      number of databases. Identified eligible studies were selected and then evaluated
      on a broad set of HRQOL predetermined criteria by four reviewers. Thirty-one
      randomised controlled trials involving 9683 colorectal cancer patients were
      identified. Nearly all studies dealt with metastatic patients and principally
      compared different chemotherapy regimens. The HRQOL tool most often used was the
      European Organisation for Research and Treatment of Cancer, Quality of Life
      Questionnaire-Core 30 (EORTC QLQ-C30), which was used in 48% of the studies. Some
      methodological limitations were identified: 39% of the RCTs did not report HRQOL
      compliance at baseline and 52% did not give details on missing data. A rationale
      for using a specific HRQOL measure was given in only 10% of the studies. Whilst
      HRQOL assessment is a potential valuable source of information in understanding
      the impact of colorectal cancer, a number of methodological shortcomings have to
      be further addressed in future studies.

PMID- 14728933
TI  - Adherence to the guidelines of the CCCE in the treatment of node-positive breast
      cancer patients.
AB  - Guidelines are tools to improve the quality of care in daily practice. To
      accomplish adherence, active implementation is needed. The effect of audit, group
      oriented feedback and educational activities to increase guideline adherence were
      investigated in this study. Treatment according to a guideline for premenopausal
      node-positive breast cancer patients from 1988 to 1992 (P1) and from 1996 to 1998
      (P2) was assessed using the following indicators: percentage of patients with
      breast-conserving surgery, secondary surgery, > or = 10 reported resected
      axillary lymph nodes, reported tumour differentiation grade, reported hormonal
      receptor status, chemotherapy received (CT), start of CT < or = 28 days after
      surgery, Dose Intensity (DI) > or = 85% and completion of CT < or = 1 week beyond
      the ideal duration of CT. Data were audited from patients' records. The first
      audit resulted in a quality programme with feedback focused on the delivery of
      chemotherapy and resected axillary lymph nodes and educational sessions. A
      Fisher's exact test was used to estimate significant differences between the two
      time periods. In P1, 323 patients and in P2, 155 patients were eligible for
      treatment according to the guideline. The percentage of patients with > or = 10
      lymph nodes improved from 65.3 to 81.3% (P=0.0004), as did the percentage with a
      reported oestrogen receptor (ER) status, from 84.8 to 96.8% (P=0.00004),
      progesterone receptor (PR) status from 82.3% to 97.4% (P<0.000001) and with a DI
      > or = 85%, from 74.9 to 93.9% (P=0.000003). Adherence varied between the
      hospitals. In conclusion, significant improvements were observed for the
      indicators of resected axillary lymph nodes and DI of chemotherapy, which may be
      attributed to the quality programme. Repeated assessment of the adherence to the
      guideline is important to observe changes and interhospital variations in order
      to remain focused on areas for improvement.

PMID- 14728934
TI  - Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and
      topoisomerase II alpha status as predictive markers in breast cancer patients
      treated with neoadjuvant anthracycline-based chemotherapy.
AB  - The aim of this study was to evaluate the predictive value of five different
      biological factors in breast cancer patients treated with neoadjuvant
      anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston
      Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell
      proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha
      (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and
      TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR).
      119 patients with operable breast cancer were treated with six cycles of FEC (100
      5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500
      mg/m2). Tumour response was assessed clinically and by computed tomography (CT)
      scan, then by pathological assessment. The clinical overall response (OR) was
      80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16%
      of CR. A pathological CR was demonstrated in 13% of the patients according to the
      Sataloff classification. In the multivariate analysis, the absence of HR
      expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour
      grade was predictive for a pathological CR. Overexpression or amplification of
      HER2 or Topollcalpha were not predictive of response.

PMID- 14728935
TI  - Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from
      sentinel lymphonodectomy and early excision of their nodal disease.
AB  - Early versus delayed excision of lymph node metastases is still being assessed in
      malignant melanoma. In the present retrospective, multicentre study, the outcome
      of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with
      the outcome of 623 patients with delayed lymph node dissection (DLND) of
      clinically enlarged lymph node metastases. In order to avoid the lead-time bias,
      survival was generally calculated from the excision of the primary tumour.
      Survival curves were constructed using the Kaplan-Meier product-limit estimate.
      Cox's proportional hazards model was used to perform a multivariate analysis of
      factors related to overall survival. Compared with SLNE and early performed
      complete lymph node dissection, DLND yielded a significantly higher number of
      lymph node metastases. Median and mean tumour thickness were nearly identical in
      the two therapy groups. The estimated 3-year overall survival rate was 80.1+/
      2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and
      67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/
      5.4%, respectively). The difference between the two survival curves was
      statistically significant (P=0.002). Using multifactorial analysis, SLNE
      (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness
      category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent
      predictors of overall survival. The location of the primary tumour (P=0.59) was
      non-significant. Considering only those centres with sufficient data for
      epidermal ulceration, this risk factor was also significant. In cutaneous
      malignant melanoma, early excision of lymphatic metastases, directed by the
      sentinel node procedure, provides a highly significant overall survival benefit.

PMID- 14728936
TI  - Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer
      patients: assessment of acute toxicity and treatment compliance. Report of the
      22921 randomised trial conducted by the EORTC Radiotherapy Group.
AB  - The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four
      arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT)
      versus preoperative radiation (XRT) and the value of additional postoperative
      chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We
      report on the preoperative toxicity, treatment compliance and early deaths (all
      deaths up to 30 days after surgery) of the two treatment modalities in patients
      who were entered into trial before January 2001. In the XRT Group (group A),
      patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group
      B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For
      each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20
      mg/m2/day were given. 398 and 400 patients started treatment in groups A and B,
      respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in
      groups A and B, respectively (P<0.005). The other side-effects remained unchanged
      or were only marginally increased. The compliance with RT was 98.5 and 95.5% in
      groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received
      95-105% of the planned CT doses at the first and second courses, respectively. 6
      patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died
      within the 30 days after surgery in both groups. At the doses recommended in the
      protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the
      amount of acute toxicity. However, the compliance with the radiation protocol or
      the feasibility of surgery did not decrease.

PMID- 14728937
TI  - The content and amount of information given by medical oncologists when telling
      patients with advanced cancer what their treatment options are. palliative
      chemotherapy and watchful-waiting.
AB  - This study aimed to determine the content and the amount of information given by
      medical oncologists when proposing palliative chemotherapy and whether this
      information given is influenced by patient or physician background
      characteristics. In a prospective study, 95 patients with incurable cancer were
      interviewed before they consulted their medical oncologist. Their first
      consultation was audiotaped, and their eventual decision scored. A coding scheme
      comprised six categories of information given during the consultation. Medical
      oncologists mentioned or explained the disease course (53%), symptoms (35%) and
      prognosis (39%). Most patients were told about the absence of cure (84%).
      Watchful-waiting was mentioned to only half of the patients, either in one
      sentence (23%) or explained more extensively (27%). Multilevel analysis revealed
      that the patients' age, patient's marital status, and consulting in an academic
      hospital explained 38% of the amount of information given. Most of the
      physicians' attention is spent on the 'active' treatment option. Older patients,
      married patients and patients in academic hospitals receive more information.

PMID- 14728938
TI  - Immunity against vaccine-preventable potentially neurotropic diseases in children
      treated for malignant brain tumours with HIT-91 chemo- and radiotherapy.
AB  - Following surgery, chemotherapy and/or irradiation, patients with malignant brain
      tumours are at risk of neurotropic diseases, although these are partly vaccine
      preventable. In a retrospective, controlled, observational study, the impact of
      the German-Austrian chemo- and radiotherapy protocol (HIT-91) on antibody
      concentrations against vaccine-preventable diseases and on vaccination behaviour
      was analysed. A significant level of seronegativity for measles- and mumps-IgG,
      and a reduced protection induced by inactivated vaccines was observed after HIT
      91 therapy. Failure of seroconversion following measles and mumps live
      vaccinations was assessed in the HIT-91-treated group and in a group with benign
      brain tumours (BBT). Analysis of cellular immunological parameters revealed
      significant aberrations in the HIT-91-treated group 36 months after completion of
      HIT-91 therapy. A retrospective analysis of the patient's vaccination history
      revealed an incorrect risk perception concerning the choice of vaccinations. We
      therefore recommend clinical vaccination with serosurveillance in patients who
      have undergone treatment for brain tumours.

PMID- 14728939
TI  - Predictive value of rectal bleeding for distal colonic neoplastic lesions in a
      screened population.
AB  - The aim of this study was to determine the diagnostic value of rectal bleeding
      for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an
      average-risk population. A cross-sectional survey was conducted among individuals
      aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a
      multicentre randomised trial of FS screening for CRC. Sensitivity, specificity
      and positive predictive value (PPV) of rectal bleeding for large distal adenomas
      or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients
      examined (15% of those with large adenomas and 29% of those with CRC). The risk
      of CRC was increased when bleeding was associated with an altered bowel habit:
      odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the
      corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal
      bleeding carries an increased risk of distal neoplastic lesions. However, most
      lesions are detected among asymptomatic subjects. This finding suggests that
      screening represents the optimal strategy to detect CRC or large adenomas in the
      distal colon in the targeted age range.

PMID- 14728940
TI  - Association of brain tumours with other neoplasms in families.
AB  - We used the nationwide Swedish Family-Cancer Database to analyse the association
      of histology-specific brain tumours with other cancers in family members. Among 0
      68-year-old offspring, 9414 patients with brain tumours were identified from 1961
      to 2000, of whom, 3387 parents were diagnosed with any primary neoplasm.
      Astrocytoma, meningioma and neurinoma were the main histological types. Increased
      standardised incidence ratios (SIRs) were found for brain tumours in association
      with cancers at sites that are known features in recognised syndromes, such as
      haemangioblastoma and renal cancer in von Hippel-Lindau disease. In addition, an
      association between astrocytoma and melanoma was recognised. Among as yet unknown
      clustering, neurinoma was associated with testicular cancer and myeloma;
      meningioma was associated with cervical cancer; astrocytoma was associated with
      prostate cancer; ependymoma was associated with breast cancer. Although some of
      these may feature a true tumour cluster, they need to be confirmed in another
      setting.

PMID- 14728941
TI  - Cancer aggregation and complex segregation analysis of families with female non
      smoking lung cancer probands in Taiwan.
AB  - Previous studies have found that having a first-degree blood relative with lung
      cancer was a possible predictor of lung cancer risk, but some studies have
      indicated that the association is non-significant or only significant for a
      subset of the studied population. To determine the familial aggregation and
      whether there is any evidence for a gene controlling the susceptibility to
      developing lung cancer in female non-smokers, multiple logistic regression
      methods for estimating covariate effects and maximum likelihood segregation
      analyses were performed using data from 216 female non-smoking lung cancer
      probands (2328 individuals) in a population-based case-control study. Having a
      family history of lung cancer was found to be a significant predictor of lung
      cancer for non-smoking females (Adjusted Odds Ratio (OR)=5.7, 95% Confidence
      Interval (CI)=1.9-16.9). Having a female relative with lung cancer (adjusted
      OR=14.4, 95% CI=2.7-75.5) was more strongly associated with the lung cancer risk
      than was having a male relative with lung cancer. This association was stronger
      for probands aged less than 60 years at onset (adjusted OR=11.2, 95% CI=2.2
      56.9). All of the Mendelian models fitted the data significantly better than the
      sporadic (no major type) model or the environmental model (P<0.00l). The
      Mendelian codominant models provided the best fit of the data for the early onset
      probands and showed a stronger effect for a major susceptibility locus for non
      smoking lung cancer probands. The results of this study provide evidence that a
      rare autosomal codominant gene may influence the risk lung cancer in non-smoker
      and is responsible for the familial aggregation observed in non-smoking lung
      cancer patients.

PMID- 14728942
TI  - Smad2 suppresses the growth of Mv1Lu cells subcutaneously inoculated in mice.
AB  - Smad2 and Smad3 are intracellular signal transduction proteins of importance in
      transforming growth factor-beta (TGFbeta)-mediated inhibition of epithelial cell
      proliferation. Inactivating mutations in the Smad2 and Smad3 genes have been
      found in various human malignancies. Here, we show that expression of Smad2 leads
      to the inhibition of growth of Mv1Lu cells inoculated with Matrigel
      subcutaneously (s.c.) in severe combined immunodeficient (SCID) mice. In
      histological appearance, the Matrigel plugs with Smad2-transfected cells showed
      strongly reduced cell density, proliferation and angiogenesis compared with the
      small tumour nodules of similar size formed by the vector- or Smad3-transfected
      cells. The histological appearance of vector- and Smad3-transfected cells
      inoculated in mice was identical. Overexpression of Smad2 and Smad3 in Mv1Lu
      cells led to the inhibition of cell growth in three-dimensional cultures when
      compared with vector-transfected cells. Overexpression of Smad2 and Smad3 also
      decreased the hyperphosphorylation of pRb in Smad-transfected cells. Thus,
      increased expression of Smad2 leads to inhibition of Mv1Lu cell proliferation and
      a reduction in the growth of the Smad2-expressing cells inoculated in mice.

PMID- 14728943
TI  - Prevalence of liver tumours in HIV-1 tat-transgenic mice treated with urethane.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein stimulates cell
      proliferation, inhibits apoptosis, displays angiogenic functions and is believed
      to be involved in the pathogenesis of Kaposi's sarcoma (KS) and other tumours
      arising in AIDS patients. Tat-transgenic (TT) mice, which constitutively express
      Tat in all tissues and organs, may therefore be predisposed to tumorigenesis. To
      test this hypothesis, we treated TT mice with urethane, a general carcinogen
      inducing tumours of various organs. The results indicate that, after injection of
      urethane, the incidence of lung tumours and lymphomas is not significantly
      different in the TT and control (CC) mice, whereas liver preneoplastic lesions
      and tumours show a significantly greater incidence in TT than in CC mice. This
      remarkable carcinogenic effect of urethane for the liver may be due to a tat
      induced predisposition, manifested as a liver cell dysplasia (LCD), spontaneously
      affecting most of the TT mice. LCD may exert a promoting effect by stimulating
      proliferation of cell clones initiated by the mutagenic effect of urethane. In
      addition, LCD, which is associated with aneuploidy and chromosome instability,
      may enhance the progression to malignancy of the preneoplastic lesions induced by
      urethane. Interestingly, a significantly greater incidence of vascular ectasias
      and haemangiomas was detected in the liver of urethane-treated TT mice, most
      likely due to the marked angiogenic properties of Tat. This study suggests a role
      for Tat in the promotion and progression of tumours initiated by exogenous and
      endogenous carcinogens in HIV-1-infected patients, thereby contributing to the
      tumorigenesis in the course of AIDS.

PMID- 14728944
TI  - Combretastatin A-4 phosphate enhances CPT-11 activity independently of the
      administration sequence.
AB  - We evaluated the effect of different intervals and sequences of the vascular
      targeting agent combretastatin A-4 disodium phosphate (CA4DP) and CPT-11
      administration on tumour growth delay and intratumoral uptake of CPT-11 using a
      syngeneic rhabdomyosarcoma tumour model. Irrespective of the administration
      sequence, the combination of CA4DP and CPT-11 significantly increases tumour
      growth delay in comparison with both drugs alone (P<0.001). Intratumoral CPT-11
      concentration generally decreased (up to 5-fold) in the combination groups, while
      SN-38, the active metabolite of CPT-11, increased up to 9-fold. However, the
      increased amount of intratumoral SN-38 trapping after CA4DP injection did not
      correlate with the observed tumour growth delay. In conclusion, CA4DP
      significantly enhances the antitumour effect of CPT-11, which is not greatly
      influenced by the administration sequence, and which lacks a correlation with the
      intratumoral trapping of CPT-11 or SN-38. Mechanisms other than trapping are
      likely to be involved in the chemosensitising capacity of CA4DP.

PMID- 14728945
TI  - Improved targeting of platinum chemotherapeutics. the antitumour activity of the
      HPMA copolymer platinum agent AP5280 in murine tumour models.
AB  - AP5280 is a novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound
      platinum (Pt) therapeutic designed to increase the therapeutic index relative to
      conventional, small-molecule platinum agents. The platinum-polymer construct
      accumulates in solid tumours on the basis of increased capillary permeability.
      The bound platinum moiety is present as an N,O-Pt chelate at the distal end of a
      tetrapeptide linker, glycine-phenylalanine-leucine-glycine, and the weight
      average molecular weight (Mw) of the construct is 22 kDa. The antitumour activity
      and toxicity of AP5280 were assessed in the syngeneic murine B16F10 and Lewis
      lung tumour models, and in the human ovarian carcinoma 2008 and head and neck
      squamous carcinoma UMSCC10b xenograft models. The maximum tolerated dose (MTD) of
      AP5280 was 6-fold greater than that of carboplatin (CBDCA) in vivo. AP5280 was
      active in all four tumour models, and it displayed a higher therapeutic index
      than CBDCA in each of these tumour models. The antitumour effect of AP5280 given
      at 16% of its MTD was equivalent to that produced by a MTD of CBDCA. Thus,
      consistent with the design goal for this drug, and despite being less potent than
      CBDCA, AP5280 produced less systemic toxicity relative to its antitumour activity
      and thus has a greater therapeutic index. On the basis of the improved
      therapeutic index evidenced in these models, AP5280 has been advanced into
      clinical trials.

PMID- 14728946
TI  - Anticancer drug response and expression of molecular markers in early-passage
      xenotransplanted colon carcinomas.
AB  - Despite some success in the treatment of colorectal carcinomas, novel rational
      therapies targeting specific cancer-related molecules are under development and
      urgently needed. These approaches need careful preclinical evaluation in models
      that closely mirror the clinical situation. Therefore, we established a panel of
      15 xenotransplantable tumours directly from fresh surgical material. We showed
      that both the histology and expression of tumour-associated markers (Epithelial
      Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could
      be maintained during passaging in nude mice. Xenotransplanted tumours were
      characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for
      5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for
      oxaliplatin. 5 patients out of 15 were treated with cytostatics because of
      synchronous metastases. The response to chemotherapy in these patients coincided
      very closely with the response of the individual xenografts. All of the
      xenografts expressed the proliferation marker Ki67 and the nuclear enzyme,
      Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts
      also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme
      Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly,
      the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a
      low response rate towards oxaliplatin. This observation needs further
      confirmation using a larger number of tumours. In conclusion, we were able to
      establish transplantable xenografts suitable to mimic the clinical situation.
      These well characterised models are useful tools for the preclinical development
      of novel therapeutic approaches and for investigating translational research
      aspects.

PMID- 14728948
TI  - Pelvic trauma management within the UK: a reflection of a failing trauma service.
AB  - During the past 2-3 years it has become increasingly difficult for specialist
      pelvic centres to provide appropriate treatment for patients. Recent data from 3
      such units has highlighted unacceptable delays from referral to operation. This
      article presents this data, analyses the reasons for the delays and the
      consequences. The focus on waiting list targets is deflecting resources away from
      specialist trauma services (including pelvic units) and has resulted in serious
      interruptions in treatment. Urgent action is required to prevent the management
      of these patients being compromised.

PMID- 14728949
TI  - Hypothermia in the trauma patient.
AB  - Hypothermia is a common finding in severely injured patients. Historically
      described as a consequence of wartime casualties where cold exposure was common,
      this topic has resurfaced in the trauma literature because of the increasing
      recognition of the morbidity and mortality associated with hypothermia.
      Hypothermia, along with acidosis and coagulopathy, has been identified as a
      component of the "lethal triad" in injured patients, and has been shown to
      contribute to increased mortality in these patients. Decreases in core
      temperature during the course of initial evaluation and resuscitation are common,
      and can contribute to poor outcomes in the injured patient. As induced
      hypothermia has been shown to be beneficial in some clinical situations, recent
      animal studies have attempted to investigate whether hypothermia in the trauma
      patient has any beneficial effects. This review examines the incidence and
      pathophysiology of hypothermia, and discusses mechanisms of heat loss and
      rewarming techniques that can be utilized in the trauma patient.

PMID- 14728950
TI  - Pelvic and acetabular fractures in the United Kingdom: a continued public health
      emergency.
AB  - In 1996 the quality of the early management of 100 consecutive patients referred
      to the SW Thames regional pelvic and acetabular unit between 1989 and 1992 was
      studied. The management of these patients was assessed in four specific areas,
      and guidelines were laid down. It was found that in 56% of patients the early
      management did not meet these suggested standards, with 34% having deficiencies
      in more than one area. These results were presented and published. Five years
      later, the early management of a further 100 consecutive referrals was assessed
      using these same guidelines, in order to close the audit loop. The treatment of
      57% of patients still did not reach the guideline standards, but the number with
      problems in more than one area fell to 20%. There has been improvement in the
      early management of pelvic and acetabular injuries. The use of external fixation
      in cases of severe haemorrhage increased, but frames were often poorly applied.
      Early communication with the specialist centre was encouraged but unfortunately
      there was still an unacceptable delay in referral. The frequency of delayed
      referral actually increased during the 5 years between study groups.

PMID- 14728951
TI  - Haemobilia after penetrating and blunt liver injury: treatment with selective
      hepatic artery embolisation.
AB  - Although traumatic haemobilia is uncommon and occurs in less than 3% of liver
      injuries, the magnitude of the bleeding may result in life-threatening
      complications. This study evaluated the efficacy of selective hepatic artery
      embolisation (HAE) in the control of bleeding in patients with traumatic
      haemobilia. The demographic, clinical and angiographic data on all patients with
      traumatic haemobilia were obtained from a prospectively documented database of
      patients undergoing visceral angiography for liver haemorrhage between 1967 and
      2002. During the 36-year period under review, 30 patients were found to have
      haemobilia on selective hepatic angiography. Ten of these 30 patients had
      haemobilia due to accidental non-iatrogenic trauma and form the basis of this
      study. In 8 of the 10 patients haemobilia resulted from penetrating liver
      injuries and two patients had blunt trauma. The mean delay between the initial
      injury and the diagnosis of haemobilia was 23.5 (range 1-120) days. The mean
      blood loss before angiography was 8 (range 3-19) units. Six patients were treated
      successfully with selective hepatic arterial embolisation, three required surgery
      and one resolved without any intervention. There were no deaths and no
      complications resulting in long term sequelae. Traumatic haemobilia is an
      uncommon but life-threatening complication of liver injury. Selective arterial
      embolisation is the initial treatment of choice with a substantial rate of
      success and a low incidence of serious complications.

PMID- 14728952
TI  - Primary repair of blunt pancreatic transection.
AB  - A 19-year-old female patient with blunt traumatic transection of the pancreas
      underwent successful primary repair of the pancreas and main pancreatic duct. A
      literature review revealed 14 previously reported such cases. Primary repair of
      the main pancreatic duct is feasible in selected patients. A wider experience
      will help to determine the method's role among such established surgical
      procedures as distal pancreatectomy, internal drainage, and minimally invasive
      transpapillary stent techniques.

PMID- 14728953
TI  - Bacterial translocation, endotoxaemia and apoptosis following Pringle manoeuvre
      in rats.
AB  - BACKGROUND: Intraoperative occlusion of the hepatoduodenal ligament (Pringle
      manoeuvre (Pm)) is often employed for the reduction of blood loss during liver
      surgery. No data exist to date on the effects of Pm on mucosal barrier
      dysfunction, systemic bacterial translocation (BT), endotoxaemia and apoptosis.
      MATERIALS AND METHODS: Sixty-five male Wistar rats in three groups: I (n=25)
      controls, II (n=20) sham operation, III (n=20) occlusion of the hepatoduodenal
      ligament (Pm). Tissue samples from mesenteric lymph nodes (MLNs), liver, lungs
      and spleen were analysed after 30 min and at 24 h. Endotoxin was measured in
      portal and aortic blood and routine haematological and biochemical parameters
      were measured before and after Pm. RESULTS: No differences were found in the
      blood parameters before and after Pm, but a significant increase in contaminated
      MLNs and liver was noted. All cultured bacteria were enteric in origin. Portal
      and aortic endotoxin were significantly increased. Overall the ileal architecture
      remained intact in all specimens studied and no significant pathology was
      observed. The ABC increased after Pm significantly (P<0.01). CONCLUSION:
      Normothermic Pm of 30 min duration results in immediate and delayed gut barrier
      failure by significantly increasing BT and endotoxaemia which might be attributed
      to portal stasis leading to intestinal congestion as well as temporary liver
      ischaemia. Apoptosis increased significantly 30 min after performing the Pm.

PMID- 14728954
TI  - Surgical fixation of intra-articular fractures of the distal humerus in adults.
AB  - We reviewed 15 adult patients with intra-articular fractures of the distal
      humerus treated over a period of 2 years. All patients underwent primary open
      reduction and internal fixation, which included 11 double plating procedures. The
      fractures were classified according to the AO/ASIF system. Patient outcome was
      assessed subjectively by scoring the patients' residual symptom of pain and their
      overall satisfaction of the treatment received. Objective assessment was
      performed using the Mayo Elbow Performance Index (range of motion, assessment of
      functional status, pain and stability of the joint). At a mean follow-up of 12.3
      months, 7 patients were rated as excellent; 6, as good; one, as fair; and one, as
      poor. These cases had an average arc of flexion of 109.7 degrees. The sub-group
      of type C fractures without revision surgery had a mean flexion arc of 110.7
      degrees (95-140 degrees ), with 100% Good to Excellent scores. Complications
      included two post-operative ulnar nerve neuropraxia, one wound infection, and one
      fracture fibrous non-union. Three patients required revision surgery which
      included a total elbow arthroplasty for implant failure, whilst four patients
      (including the patient with the subsequent arthroplasty) required joint
      mobilisation procedures for residual stiffness.

PMID- 14728955
TI  - Delayed and non-union of the humeral diaphysis--compression plate or internal
      plate fixator?
AB  - In a retrospective study, two groups of patients with delayed or non-union of the
      humeral diaphysis were compared. In group A, a 4.5-mm low-contact dynamic
      compression plate (LCDCP) was used for internal fixation and in group B, an
      internal plate fixator with locked screws was used. In all patients autologous
      bone grafting was performed. Group A consisted of 14 patients (mean age 38.9
      years) and group B consisted of 19 patients (mean age 54.3 years). The mean
      duration of the delayed or non-union was 9.3 months (range 3-26 months) in group
      A and 24.8 months (range 3-216 months) in group B. In group A an average of 1.1
      (range 0-2) previous operations had been performed, and in group B an average of
      1.6 (range 0-4). One primary nerve palsy was diagnosed in group A and six in
      group B. Although the patients of group B were older, had longer-lasting non
      unions, more previous operations and more severe initial injuries, only in group
      A was there a hardware failure due to osteoporosis which required re
      osteosynthesis. All other patients showed bony consolidation without further
      operations. The LCDCP and the internal plate fixator both showed high
      consolidation rates, but we feel that the internal plate fixator may be the more
      reliable implant, especially in patients with poor bone stock.

PMID- 14728956
TI  - Management of upper limb arterial injury without angiography--Chennai experience.
AB  - We present our experience and observations in the management of upper limb
      arterial injury in a tertiary trauma care centre of a University Hospital in a
      developing country from January 2000 to January 2002. In this retrospective
      study, we had treated 27 patients (identified from trauma register) with upper
      extremity vascular injuries. Clinical examination and Doppler pressure studies
      were our prime modalities of investigation. Angiography was not employed. Our
      immediate limb salvage rate was 100%. Two patients developed complications during
      a mean follow up of 70 days with one requiring amputation. We thereby emphasise
      the fact that good results can be obtained by thorough clinical examination and
      Doppler evaluation and prompt surgery without the need for angiography in upper
      limb vascular trauma.

PMID- 14728957
TI  - A traction jig for reduction of distal radial fractures.
AB  - A traction jig is described which facilitates the closed reduction of extra
      articular distal radial fractures and which maintains the reduction whilst a
      plaster cast is applied. The jig is suitable for use by a single operator in an
      Accident and Emergency department setting.

PMID- 14728958
TI  - The posterolateral corner of the knee. Anatomy, biomechanics and management of
      injuries.
AB  - The structures within the posterolateral corner of the knee have recently been
      "re-discovered" providing a very important role in maintaining the stability of
      the knee. Injury to the posterolateral corner is not common but neither is it
      rare; it is usually damaged in combination with rupture of one of the cruciate
      ligaments in direct and indirect trauma to the knee. When reconstructing a knee
      to restore stability following such injuries, it is important to recognise damage
      to the posterolateral corner so that this can be corrected. Ignored damage to
      this region may result in continuing knee instability and resultant failure of
      cruciate ligament reconstruction. We present a review of the anatomy and
      biomechanics of the structures in the posterolateral corner. This is then related
      to the diagnosis of injuries to the region via history, examination and imaging.
      We then discuss the management of injuries to the posterolateral corner
      describing our preferred method of repair.

PMID- 14728959
TI  - Traumatic patella tendon rupture: early mobilisation following surgical repair.
AB  - This study aims to demonstrate that postoperative immobilisation in a cast is
      unnecessary following suture repair of the patella tendon and retinacula
      protected by a cerlage wire. We present 11 patients mean age 42 years evaluated
      at a mean of 26 months (range 14-38 months). The mean Lysholm knee score at
      review was 97 (range 92-100). The mean Insall Salvati measurement (length
      patella/length tendon (LP/LT)) was 1 (range 0.95-1.1). No patients had fixed
      flexion deformities or demonstrated an extensor lag and the average range of
      motion was 0-137 degrees. The difference between the operated and control knee at
      the time of assessment was: a mean loss of power of 6% (range 2-11) when
      measuring concentric extension and a mean loss of 7% power (range 13 to an
      increase of 12) in concentric flexion. We conclude that primary repair protected
      with a cerlage wire and early mobilisation gives excellent results in the
      treatment of isolated traumatic patella tendon ruptures and cast immobilisation
      postoperatively is not required.

PMID- 14728960
TI  - Hypovolaemic shock due to a fracture of the superior pubic ramus in a young man.

PMID- 14728961
TI  - Infected total knee arthroplasty complicated with mycotic aneurysms. A case
      report and review of the literature.

PMID- 14728962
TI  - Arthroscopically assisted internal fixation of a talus body fracture.

PMID- 14728963
TI  - Elbow dislocation with ipsilateral open radial and ulnar diaphyseal fractures--a
      rare combination.

PMID- 14728964
TI  - Unexplained bilateral extensor and unilateral flexor acute compartment syndrome
      of the forearm.

PMID- 14728965
TI  - Trauma resuscitation time.

PMID- 14728966
TI  - Management of pertrochanteric fractures in the elderly patients with an external
      fixation. Injury, vol. 32 (Suppl. 4), pp. 115-128 (2001).

PMID- 14728967
TI  - Use of allograft for the large Hill-Sachs lesion associated with anterior
      glenohumeral dislocation.

PMID- 14728969
TI  - Intrapelvic protrusion of guidewire during fixation of fracture neck of femur.

PMID- 14728974
TI  - Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte
      model.
AB  - In order to assess the risk to mammals of a chronic exposure to imidacloprid
      (IMI), we investigated its absorption with the human intestinal Caco-2 cell line.
      Measurements of transepithelial transport revealed an apparent permeability
      coefficient of 21.6 x 10(-6) +/- 3.2 x 10(-6) cm/s reflecting a 100% absorption.
      The comparison of apical to basal (A-B) and basal to apical (B-A) transports
      showed that the monolayer presents a basal to apical polarized transport. Studies
      of apical uptake demonstrated that the transport was concentration-dependent and
      not saturable from 5 to 200 microM. Arrhenius plot analysis revealed two apparent
      activation energies, Ea(4-12 degrees C) = 63.8 kJ/mol and Ea(12-37 degrees C) =
      18.2 kJ/mol, suggesting two temperature-dependent processes. IMI uptake was
      equivalent when it was performed at pH 6.0 or 7.4. Depletion of Na+ from the
      transport buffer did not affect the uptake, indicating that a sodium-dependent
      transporter was not involved. Decrease of uptake with sodium-azide or after cell
      surface trypsin (Ti) treatment suggested the involvement of a trypsin-sensitive
      ATP-dependent transporter. Investigations on apical efflux demonstrated that
      initial velocities paralleled the increase of loading concentrations. A cell
      surface trypsin treatment did not affect the apical efflux. The lack of effect
      when the efflux was performed against an IMI concentration gradient suggested
      that an energy-dependent transporter was involved. However, the inhibition of P
      glycoproteins (P-gp) and multidrug resistance-associated proteins (MRP) by taxol,
      vincristine, and daunorubicine had no effect on IMI intracellular accumulation
      suggesting the involvement of transporters distinct from classical ATP binding
      cassette transport (ABC-transport) systems. All results suggest that IMI is
      strongly absorbed in vivo by inward and outward active transporters.

PMID- 14728975
TI  - Evaluation of ubiquinone concentration and mitochondrial function relative to
      cerivastatin-induced skeletal myopathy in rats.
AB  - As a class, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can
      potentially cause skeletal myopathy. One statin, cerivastatin, has recently been
      withdrawn from the market due to an unacceptably high incidence of
      rhabdomyolysis. The mechanism underlying statin-induced myopathy is unknown. This
      paper sought to investigate the relationship among statin-induced myopathy,
      mitochondrial function, and muscle ubiquinone levels. Rats were administered
      cerivastatin at 0.1, 0.5, and 1.0 (mg/kg)/day or dose vehicle (controls) by oral
      gavage for 15 days. Samples of type I-predominant skeletal muscle (soleus) and
      type II-predominant skeletal muscle [quadriceps and extensor digitorum longus
      (EDL)], and blood were collected on study days 5, 10, and 15 for morphological
      evaluation, clinical chemistry, mitochondrial function tests, and analysis of
      ubiquinone levels. No histological changes were observed in any of the animals on
      study days 5 or 10, but on study day 15, mid- and high-dose animals had necrosis
      and inflammation in type II skeletal muscle. Elevated creatine kinase (CK) levels
      in blood (a clinical marker of myopathy) correlated with the histopathological
      diagnosis of myopathy. Ultrastructural characterization of skeletal muscle
      revealed disruption of the sarcomere and altered mitochondria only in myofibers
      with degeneration, while adjacent myofibers were unaffected and had normal
      mitochondria. Thus, mitochondrial effects appeared not to precede myofiber
      degeneration. Mean coenzyme Q9 (CoQ9) levels in all dose groups were slightly
      decreased relative to controls in type II skeletal muscle, although the
      difference was not significantly different in most cases. Mitochondrial function
      in skeletal muscle was not affected by the changes in ubiquinone levels. The
      ubiquinone levels in high-dose-treated animals exhibiting myopathy were not
      significantly different from low-dose animals with no observable toxic effects.
      Furthermore, ubiquinone levels did not correlate with circulating CK levels in
      treated animals. The results of this study suggest that neither mitochondrial
      injury, nor a decrease in muscle ubiquinone levels, is the primary cause of
      skeletal myopathy in cerivastatin-dosed rats.

PMID- 14728976
TI  - Developmental toxicity of dioxin to mouse embryonic teeth in vitro: arrest of
      tooth morphogenesis involves stimulation of apoptotic program in the dental
      epithelium.
AB  - Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can
      arrest molar tooth development in rats after in utero and lactational exposure,
      and that the sensitive stage is temporally restricted. To define the stage in
      which TCDD is able to arrest tooth development and the cellular background of the
      effect, mouse embryonic molar tooth explants including various early
      developmental stages from initiation to late cap stage were exposed to TCDD in
      organ culture. TCDD did not inhibit morphogenesis of the first molar teeth
      including the early bud-staged E12 first molars, but the teeth were smaller than
      in control cultures. Accordingly, the second molars underwent morphogenesis in
      the presence of TCDD when explanted at E15 when they were at the bud stage. TCDD
      arrested their development when explanted at E14 when they had not yet reached
      the early bud stage. Immunohistochemical localization of incorporated
      bromodeoxyuridine in cultured E14 teeth showed that TCDD did not affect cell
      proliferation. Localization of apoptosis by terminal deoxynucleotidyl transferase
      (TdT)-mediated nick end labeling (TUNEL) method revealed that TCDD enhanced
      apoptosis of dental epithelial cells, especially in the dental lamina of both the
      first and second molars, and in the inner dental epithelium at the cusp tips of
      the first molars. Thus, TCDD can arrest tooth development in vitro if the
      exposure starts at the initiation stage, whereas exposure at later stages leads
      to smaller tooth size and deformation of cuspal morphology. TCDD interferes with
      tooth development by stimulating apoptosis in those cells of the dental
      epithelium, which are predetermined to undergo apoptosis during normal
      development.

PMID- 14728977
TI  - Effect of thuringiensin on adenylate cyclase in rat cerebral cortex.
AB  - The purpose of this work is to evaluate the effect of thuringiensin on the
      adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'
      monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or
      54-377% by thuringiensin at concentrations of 10 microM-100 mM or 0.5-4 mM, due
      to the activation of basal adenylate cyclase activity of rat cerebral cortical
      membrane preparation. Thuringiensin also activated basal activity of a commercial
      adenylate cyclase from Escherichia coli. However, the forskolin-stimulated
      adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin
      at concentrations of 1-100 microM, thus cAMP production decreased. Furthermore,
      thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin
      (10 microM)-stimulated adenylate cyclase activity at concentrations of 10 microM,
      49% or 43% inhibition, respectively. In conclusion, this study demonstrated that
      thuringiensin could activate basal adenylate cyclase activity and increase cAMP
      concentrations in rat cerebral cortex or in a commercial adenylate cyclase.
      Comparing the dose-dependent effects of thuringiensin on the basal and forskolin
      stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak
      activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate
      cyclase.

PMID- 14728978
TI  - Plasmid DNA damage caused by stibine and trimethylstibine.
AB  - Antimony is classified as "possibly carcinogenic to humans" and there is also
      sufficient evidence for antimony carcinogenicity in experimental animals. Stibine
      is a volatile inorganic antimony compound to which humans can be exposed in
      occupational settings (e.g., lead-acid battery charging). Because it is highly
      toxic, stibine is considered a significant health risk; however, its genotoxicity
      has received little attention. For the work reported here, stibine was generated
      by sodium borohydride reduction of potassium antimony tartrate. Trimethylstibine
      is a volatile organometallic antimony compound found commonly in landfill and
      sewage fermentation gases at concentrations ranging between 0.1 and 100
      microg/m3. Trimethylstibine is generally considered to pose little environmental
      or health risk. In the work reported here, trimethylstibine was generated by
      reduction of trimethylantimony dichloride using either sodium borohydride or the
      thiol compounds, dithioerythritol (DTE), L-cysteine, and glutathione. Here we
      report the evaluation of the in vitro genotoxicities of five antimony compounds
      potassium antimony tartrate, stibine, potassium hexahydroxyantimonate,
      trimethylantimony dichloride, and trimethylstibine-using a plasmid DNA-nicking
      assay. Of these five antimony compounds, only stibine and trimethylstibine were
      genotoxic (significant nicking to pBR 322 plasmid DNA). We found stibine and
      trimethylstibine to be about equipotent with trimethylarsine using this plasmid
      DNA-nicking assay. Reaction of trimethylantimony dichloride with either
      glutathione or L-cysteine to produce DNA-damaging trimethylstibine was observed
      with a trimethylantimony dichloride concentration as low as 50 microM and L
      cysteine or glutathione concentrations as low as 500 and 200 microM,
      respectively, for a 24 h incubation.

PMID- 14728979
TI  - Uranium induces TNF alpha secretion and MAPK activation in a rat alveolar
      macrophage cell line.
AB  - Uranium is a toxic heavy metal found mainly in the nuclear industry, but it is
      also used in the manufacturing of military munitions. Inhalation studies using
      animal models have demonstrated that long-term exposure to uranium can lead to
      the development of neoplasia and fibrosis at the pulmonary level. Because it has
      been demonstrated that such effects are often associated with inflammation, the
      effect of uranium on TNFalpha, IL-1beta, and IL-10 synthesis by macrophages was
      assessed in vitro using the NR8383 cell line. Our results show that a significant
      TNFalpha secretion was induced by uranium but not by other metals such as
      gadolinium. However, IL-1beta and IL-10 secretions were unaffected by uranium
      treatment. TNFalpha secretion was detectable since 50 microM of uranium and was
      maximal after 24 h of exposure. Determination of the mechanisms of uranium
      induced TNFalpha production was assessed through the evaluation of protein
      kinases activation. Our results showed that uranium treatment induced c-Jun N
      terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)
      activation. The use of pharmacological inhibitors suggested that both p38 MAPK
      and protein kinase C (PKC) participate in the signal transduction of uranium
      induced TNFalpha secretion. The regulation of TNFalpha secretion involves
      TNFalpha mRNA accumulation at least through the stabilization of TNFalpha mRNA,
      but p38 MAPK did not appear to be involved in this stabilization. However, this
      observation does not exclude regulation of TNFalpha synthesis at the
      transcriptional level, which remains to be demonstrated. Taking together, these
      results suggest that uranium can induce TNFalpha secretion by macrophages, thus
      contributing to a better understanding of the pathological effect of uranium on
      the lung.

PMID- 14728980
TI  - Nickel-induced down-regulation of serpin by hypoxic signaling.
AB  - Nickel (Ni) carcinogenesis is thought to involve gene chip silencing by
      epigenetic mechanisms. Serpina3g, a member of the mouse serpin family, was among
      the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells
      based on the Affymetrix gene chip. Serpina3g down-regulation was controlled by a
      hypoxia inducible factor (HIF) mechanism. The exposure of cells to cobalt (Co),
      hypoxia, the iron chelator deferoxamine, and the proline hydroxylase inhibitor
      dimethyloxalylglycine (DMOG) also down-regulated serpina3g transcription to
      similar extents as soluble Ni exposure. These results support the mounting
      experimental evidence that water-soluble Ni compounds have a predominant effect
      on hypoxia signaling because of their ability to interfere with Fe homeostasis in
      the cell. Trichostatin A (TSA) and 5-azacytidine (5-AzaC) reactivated the Ni
      silenced serpina3g gene, indicating that its silencing by Ni involved either a
      direct or indirect epigenetic mechanism. Analysis of the chromatin state of the
      serpina3g promoter by the ChIP assay revealed that exposure of mouse fibroblast
      cells to Ni resulted in the methylation of H3 lysine 9 within its promoter, as
      well as a decrease in the phosphorylation of serine 10 of H3 and a marked
      decrease in the acetylation of H3 and H4. Serpina3g gene expression returned to
      basal levels following Ni removal, suggesting that the observed silencing was a
      dynamic and reversible process.

PMID- 14728981
TI  - In vivo conjugation of nasal lavage proteins by hexahydrophthalic anhydride.
AB  - Hexahydrophthalic anhydride (HHPA), an industrially important chemical, is a
      highly allergenic compound. The aim of this work was to identify proteins in
      nasal lavage fluid (NLF) that form adducts with HHPA. Such bindings may induce
      production of specific immunoglobulin E (IgE) or affect physiological mechanisms
      of the proteins. NLF was obtained from HHPA-exposed volunteers, workers and
      exposed guinea pigs. HHPA-binding proteins were visualized with immunoblotting
      using a polyclonal antiserum against HHPA. The proteins were excised from sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, digested
      with trypsin and identified by tandem mass spectrometry (MS/MS) and database
      searches. The antiserum was found to be specific for HHPA-bound proteins. In vivo
      formed HHPA-binding proteins in humans were identified as antileukoproteinase,
      immunoglobulin G (IgG), immunoglobulin A (IgA), serum albumin and lactoferrin. In
      addition, several proteins binding to HHPA were found in NLFs from guinea pigs
      but these could not be identified from database searches. Hypotheses for
      development of airways diseases by adduction of this allergenic compound to the
      NLF proteins in humans were established.

PMID- 14728982
TI  - Expression of genes in the TGF-beta signaling pathway is significantly
      deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor
      knockout mice.
AB  - The molecular basis for the adverse biological effects of dioxin (2,3,7,8
      tetrachlorodibenzo-p-dioxin; TCDD), a pervasive environmental toxin, is largely
      unknown. TCDD is a ligand for the cytosolic aromatic hydrocarbon receptor (AHR)
      which mediates the transcriptional induction of the xenobiotic metabolizing genes
      in the CYP1 family of cytochromes P450. Previous studies have suggested that the
      AHR may carry out important functions in the cell in addition to metabolizing
      toxins. We present gene expression profiles of smooth muscle cells from wild type
      and Ahr(-/-) mice that show significant changes in the RNA levels of the
      transforming growth factor-beta3 (Tgfb3) gene and genes involved in the
      modulation and processing of TGF-beta. The RNA expression profiles support a
      hypothesis that in the wild type, the AHR represses Tgfb gene expression and
      affects the gene expression of several TGF-beta-modulating and processing genes.
      We also observed that RNA levels increased for TGF-beta2, CYP1b1, and TGF-beta
      related genes in Ahr(-/-) smooth muscle cells exposed to TCDD. These data are
      consistent with a hypothesis that TCDD stimulates the TGF-beta2 signaling pathway
      in the absence of the AHR to activate the Cyp1b1 gene. The above results provide
      a possible explanation for some of the multiple biological effects of TCDD and
      the physiological role played by the AHR in the absence of environmental agents.

PMID- 14728983
TI  - The effect of fluoride on the scavenging of organophosphates by human
      butyrylcholinesterase in buffer solutions and human plasma.
AB  - Fluoride ion is a reversible inhibitor of human butyrylcholinesterase (HuBChE)
      that is a viable drug candidate against organophosphates (OPs) toxicity. Since
      large numbers of communities in many countries are occasionally exposed to
      relatively high amount of fluoride, its effect on the kinetics of inhibition of
      HuBChE by OPs was investigated. In saline phosphate, pH 7.4, fluoride in the
      lower millimolar range significantly slowed the inhibition of HuBChE by paraoxon,
      DFP, echothiophate, soman, sarin, and VX. The kinetics of the inhibition was
      found consistent with the formation of a reversible fluoride-HuBChE complex that
      is at least 25-fold less active towards phosphorylation or phosphonylation than
      the free enzyme. Heat inactivation experiments indicate that the binding of
      fluoride to HuBChE probably involves enhanced cross-domain interaction via
      hydrogen bonds formation that may decrease enzyme activity. In spite of distinct
      structural differences among the OP used, the dissociation constants of the
      fluoride-HuBChE reversible complex varied over a narrow range (KF, 0.31-0.70 mM);
      however, KF in human plasma increased to 2.75-3.40 mM. 19F-NMR spectroscopy
      revealed that fluoride ion is complexed to plasma components, an observation that
      explains in part the apparent increase in KF. Results suggest that an estimate of
      the relative decrease in the rate of OPs sequestration in presence of fluoride
      can be obtained from the fraction of the free HuBChE (1 + [F]/K(F))(-1).
      Considering KF values in human plasma, it is concluded that the scavenging
      efficacy of OPs by HuBChE is not compromised by the normal concentration range of
      circulating fluoride ions.

PMID- 14728984
TI  - New approaches to treat PKU: how far are we?

PMID- 14728985
TI  - State-of-the-art 2003 on PKU gene therapy.
AB  - Phenylketonuria (or PKU) is a well-known and widespread genetic disease for which
      many countries perform newborn screening, and life-long dietary restriction is
      still the ultimate and effective therapy. However, the diet is complicated,
      unpalatable, and expensive. The long-term effects of diet discontinuation in
      adults, except for the serious adverse effects of maternal hyperphenylalaninemia
      upon the developing fetus, have not been systematically studied, but cognitive
      decline and neurologic abnormalities have been anecdotally reported. Thus,
      alternative approaches for PKU therapy, including gene therapy, must be further
      explored. Here we summarize past present nonviral and viral gene transfer
      approaches, both in vitro studies and preclinical animal trials, to delivering
      the PAH gene into liver or other organs as potential alternatives to life-long
      phenylalanine-restricted dietary therapy.

PMID- 14728986
TI  - Alpha-endosulfine, a positional and functional candidate gene for type 2
      diabetes: molecular screening, association studies, and role in reduced insulin
      secretion.
AB  - Impaired glucose stimulated insulin secretion is a prominent, early defect in
      type 2 diabetes. Insulin secretion is coupled to glucose metabolism by effects of
      the intracellular ATP/ADP ratio on the multimeric beta-cell potassium channel.
      The sulfonylurea receptor (SUR1 or ABCC8), the regulatory subunit of that
      channel, binds sulfonylurea agents and thus closes the channel and stimulates
      exocytosis of insulin-containing granules. alpha-Endosulfine (ENSA), has been
      proposed as the endogenous ligand for SUR1. We mapped ENSA in silico to
      chromosome 1q21 near a confirmed type 2 diabetes susceptibility locus, and
      derived the genomic structure of four exons and three introns. We identified four
      single nucleotide polymorphisms (SNP) and one insertion deletion polymorphism
      among 16 Caucasian and 16 African-American diabetic individuals. Only one SNP was
      common to both ethnic groups, and no SNP altered the coding sequence. No variant
      was associated with type 2 diabetes in Caucasian or African-American studies, but
      a single SNP in intron 3 (SNP 17) was associated with a reduced disposition index
      (insulin sensitivity x acute insulin response to glucose) in interaction with
      family membership in 126 members of 26 Caucasian families. Individuals homozygous
      for the rare allele showed a 70% reduction in insulin secretion (disposition
      index) relative to all other genotypes. Our data do not suggest that ENSA could
      explain the linkage of T2DM to this region, but ENSA SNP 17 may have an important
      role in reducing the ability of the beta-cell to compensate for reduced insulin
      sensitivity, which in turn would increase the susceptibility to T2DM.

PMID- 14728987
TI  - The transcribed endosulfine alpha gene is located within a type 2 diabetes-linked
      region on 1q: sequence and expression analysis in Pima Indians.
AB  - Endosulfine alpha (ENSA) is an endogenous ligand of the sulfonylurea receptor 1
      (SUR1) that can stimulate insulin secretion by pancreatic beta cells. Originally,
      an intronless gene coding for this protein was assigned to Chr. 14q, but more
      recent information available in public databases indicated the position of ENSA
      on 1q21. We show here that the 1q21 locus represents the expressed gene
      consisting of 6 exons, whereas the locus on Chr. 14q is apparently a pseudogene.
      The ENSA gene on 1q21 produces several alternatively spliced transcripts, and is
      located within a region linked with T2DM in diverse populations including the
      Pima Indians. We analyzed ENSA in this Native American population and identified
      seven variants, which fall into three linkage disequilibrium groups. Analysis of
      representative markers in over 1200 Pima Indians did not reveal any significant
      association with T2DM, or with differences in insulin action and insulin
      secretion in a subset of approximately 270 non-diabetic subjects. In addition, we
      did not detect any significant correlation of skeletal muscle ENSA transcript
      levels with differences in insulin action in 49 non-diabetic subjects. We
      conclude that sequence alterations in ENSA are an unlikely cause for the linkage
      of T2DM with 1q21-q23 in the Pima Indians.

PMID- 14728988
TI  - The rate of de novo galactose synthesis in patients with galactose-1-phosphate
      uridyltransferase deficiency.
AB  - Using both a continuous infusion of isotopically labeled [1-13C]galactose with a
      steady-state analysis and a single injection kinetic approach, we have calculated
      the apparent galactose appearance rate (GAR) in patients with galactose-1
      phosphate uridyltransferase deficiency and control subjects. With the steady
      state protocol, the GAR in 18 patients less than 18 years of age was 1.34+/-0.53
      mg/kg/h (mean+/-SD) and was significantly greater than the mean of 0.56+/-0.01
      mg/kg/h (p=0.004) in five patients above 18 years of age. Patients who were given
      a priming dose of [1-13C]galactose had a reduced GAR compared to those without a
      priming dose, 0.73+/-0.05 (n=9) vs 1.46+/-0.62 (n=14)mg/kg/h (p=0.005). The GAR
      in controls was lower than in patients ranging from 0.58 to 0.68 mg/kg/h in
      children and 0.07-0.09 mg/kg/h in adults. In the single bolus studies the plasma
      [13C]galactose enrichment decreased in a biexponential pattern suggesting at
      least a two-compartment system. The calculated GAR in three adult patients was
      similar to that found in them by the continuous infusion technique. The GAR in
      patients suggests the source of galactose for the continued elevation of
      galactose metabolites as well as the basis for the long-term complications in
      galactosemia despite restricted dietary galactose intake.

PMID- 14728989
TI  - Age dependence of endogenous galactose formation in Q188R homozygous galactosemic
      patients.
AB  - The age dependence of endogenous galactose formation was investigated in Q188R
      homozygous galactosemic patients (n=18; 4-38 years) using the primed continuous
      infusion approach with D-[1-13C]galactose as a substrate. Studies were conducted
      under postabsorptive conditions (fasting >10h) and good metabolic control. In the
      patients, the release of galactose from endogenous sources into plasma (R(a))
      decreased with age and ranged from 4.6 to 2.0 micromol/kg body weight per h.
      Galactitol and galactonate release rates paralleled the galactose R(a) but at a
      lower level. The mean relation of galactose, galactitol, and galactonate release
      was 10:5:1. Statistically, there was a highly significant (p<0.0001) inverse
      correlation between total galactose release (i.e., sum of R(a) plus galactitol
      and galactonate release) and age. The data (total galactose=y, age=t) were best
      fitted to the simple exponential model y=y(0)+axexp(-bt) by non-linear regression
      analysis. The parameter estimates were y(0)=3.0+/-0.2, a=6.5+/-0.4, and b=0.11+/
      0.02. The value of y(0) provides an estimate of total galactose release in adult
      patients (i.e., approximately 13 mg/kg body weight per day), summation operator
      (y(0)+a) provides an estimate for galactosemic newborns (i.e., approximately 41
      mg/kg body weight per day). The data show that significant amounts of endogenous
      galactose are formed in galactosemic patients with release rates being several
      fold higher in infants than in adults. The present findings can explain the
      persistently elevated galactose-1-phosphate levels in erythrocytes-and its age
      dependence-in galactosemic patients even when under strict dietary treatment.

PMID- 14728990
TI  - Plasma tetrahydrobiopterin and its pharmacokinetic following oral administration.
AB  - Tetrahydrobiopterin (BH(4)) is widely used as a therapeutic agent in patients
      with BH(4) deficiencies and mild forms of phenylketonuria (PKU) and there is an
      increasing need for the measurement of its plasma concentrations in patients with
      cardiovascular disorders. We measured BH(4) and total biopterin in
      dithioerythritol (DTE) pretreated plasma from four adults after oral
      administration of BH(4) (2, 10, and 20mg/kg body weight) using the differential
      iodine oxidation method. About 80% (range 64.8-92.2% ) of total biopterin was
      found as BH(4) when analyzed immediately after blood sampling. Compared with
      ascorbic acid as an antioxidant, DTE was more protective against oxidation of
      BH(4), particularly in samples stored over a period of 8 months. Without
      antioxidant (DTE or ascorbic acid) almost no BH(4) was detected. Furthermore,
      BH(4) and total biopterin were measured at different time intervals (up to 33 h
      after oral administration) and pharmacokinetic parameters T(max) (1-4h), C(max)
      (258.7-259.0 nmol/L biopterin at a dosage of 10mg/kg), and area under the curve
      (AUC=1708-1958 nmol(*)h/L up to T=10h) were estimated. The elimination half-life
      time was calculated to be 3.3-5.1h. Doubling the BH(4) dosage to 20mg/kg resulted
      in 60% higher AUC while sublingual BH(4) application (2mg/kg) resulted in 58-76%
      higher BH(4) plasma concentrations when compared with oral administration. These
      preliminary data suggest that in patients with BH(4) cofactor defects and BH(4)
      responsive phenylalanine hydroxylase deficiency, BH(4) should be given in at
      least two to three daily doses and that sublingual administration may lower the
      required BH(4) dosage and subsequently the cost of treatment. Due to inter
      individual differences in pharmacokinetic properties, in some patients with
      hyperphenylalaninemia and mild PKU plasma BH(4) levels may be not high enough to
      fully activate the liver phenylalanine hydroxylase and thus lower blood
      phenylalanine levels. Assessment of plasma BH(4) or total biopterin
      concentrations may be a good way to control the efficacy of the loading test.

PMID- 14728992
TI  - Iduronate-2-sulphatase protein detection in plasma from mucopolysaccharidosis
      type II patients.
AB  - The lysosomal storage disorder mucopolysaccharidosis type II (MPS II) is caused
      by a deficiency in the activity of the lysosomal exohydrolase iduronate-2
      sulphatase (IDS). MPS II patients present within a spectrum of clinical
      phenotypes, which reflects the dynamic balance between the level of mutant
      protein, its residual enzyme activity and the resultant level of storage product.
      In this study, we have developed an immunoquantification assay for the accurate
      detection of iduronate-2-sulphatase protein and applied this methodology to the
      analysis of mutant iduronate-2-sulphatase protein in plasma samples from MPS II
      patients. The detection limit for the assay was defined as 20 ng/ml for wild type
      iduronate-2-sulphatase, but could be extended to a detection limit of 0.3 ng/ml
      by heat denaturation of the protein/plasma sample. The mutant protein detected in
      plasma from MPS II patients displayed similar properties to heat denatured wild
      type iduronate-2-sulphatase, suggesting an altered protein conformation. The
      ratio of heat denatured to native ELISA reactivity could be used to confirm the
      diagnosis of MPS II (i.e., a ratio of >1 for normal protein and <or=1 for mutant
      protein). Notably, four of the 20 patients tested had either normal or higher
      than normal levels of iduronate-2-sulphatase protein, but this protein also
      showed evidence of conformation change. The iduronate-2-sulphatase protein level
      detected in plasma from MPS II patients showed little or no direct correlation
      with the severity of the clinical phenotype observed in these patients.

PMID- 14728991
TI  - The fate of intravenously administered tetrahydrobiopterin and its implications
      for heterologous gene therapy of phenylketonuria.
AB  - Tetrahydrobiopterin (BH(4)) is a required cofactor for the enzymatic activity of
      phenylalanine hydroxylase (PAH) and is synthesized de novo from GTP in several
      tissues. Heterologous expression of PAH in tissues other than liver is a
      potential novel therapy for human phenylketonuria that is completely dependent
      upon BH(4) supply in the PAH-expressing tissue. Previous experiments with liver
      PAH-deficient transgenic mice that expressed PAH in skeletal muscle demonstrated
      transient correction of hyperphenylalaninemia only with hourly parenteral BH(4)
      administration. In this report, the fate of intravenously administered BH(4) is
      examined. The conclusions are that (1) BH(4) administered intravenously is
      rapidly taken up by liver and kidney, and (2) uptake of BH(4) into muscle is
      relatively low. The levels of BH(4) achieved in skeletal muscle following IV
      injection are only 10% of the amount expected were BH(4) freely and equally
      distributed across all tissues. The half-life of BH(4) in muscle is approximately
      30 min, necessitating repeated injections to maintain muscle BH(4) content
      sufficient to support phenylalanine hydroxylation. The efficacy of heterologous
      muscle-directed gene therapy for the treatment of PKU will likely be limited by
      the BH(4) supply in PAH-expressing muscle.

PMID- 14728993
TI  - A naturally occurring -263G/C variant of the human AA-NAT gene and overnight
      melatonin production.
AB  - Several lines of evidence show that the daily amount of melatonin produced
      differs greatly between individuals. Any polymorphism in the gene of
      arylalkylamine N-acetyltransferase (AA-NAT), a critical enzyme involved in
      melatonin biosynthesis, may contribute to the variability of melatonin
      production. The present study investigated the possible association between
      overnight melatonin excretion and a commonly occurring -263G/C polymorphism in
      the promoter region of the human AA-NAT gene. However, we found that -263G/C
      variant had no effect on the overnight 6-OHMS excretion. In this study,
      individual genotyping for -263G/C was determined by denaturing high performance
      liquid chromatography (DHPLC) and confirmed by sequencing. The overnight urinary
      6-hydroxymelatonin sulfate (6-OHMS) excretion was quantified by enzyme-linked
      immunosorbent assay (ELISA).

PMID- 14728994
TI  - Glucocerebrosidase mutations in subjects with parkinsonism.
AB  - Recent studies showing an association between glucocerebrosidase deficiency and
      parkinsonism in Gaucher disease prompted an examination of the glucocerebrosidase
      gene sequence (GBA) and enzyme activity in brain samples from 57 subjects
      carrying the diagnosis of Parkinson disease. Alterations in GBA were identified
      in 12 samples (21%) and were more frequent among the younger subjects. These
      included eight with mutations (N370S, L444P, K198T, and R329C) and four with
      probable polymorphisms (T369M and E326K). Our findings suggest that mutations in
      glucocerebrosidase may be a risk factor for the development of parkinsonism.

PMID- 14728996
TI  - Ideas in biomedical science: reasons for the foundation of Medical Hypotheses.

PMID- 14728997
TI  - The case against antipsychotic drugs: a 50-year record of doing more harm than
      good.
AB  - Although the standard of care in developed countries is to maintain schizophrenia
      patients on neuroleptics, this practice is not supported by the 50-year research
      record for the drugs. A critical review reveals that this paradigm of care
      worsens long-term outcomes, at least in the aggregate, and that 40% or more of
      all schizophrenia patients would fare better if they were not so medicated.
      Evidence-based care would require the selective use of antipsychotics, based on
      two principles: (a). no immediate neuroleptisation of first-episode patients;
      (b). every patient stabilized on neuroleptics should be given an opportunity to
      gradually withdraw from them. This model would dramatically increase recovery
      rates and decrease the percentage of patients who become chronically ill.

PMID- 14728998
TI  - Role of androgens in mild cognitive impairment and possible interventions during
      andropause.
AB  - Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis,
      representing a state of cognitive decline associated with negligible functional
      loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing
      MCI may lead to preventive strategies that can delay the onset of AD. Many
      patients who transition into andropause report problems with their memory. There
      is strong evidence from basic sciences and epidemiological studies that both
      estrogens and androgens play a protective role in neurodegeneration. The evidence
      from small prospective clinical trials lends support to the role of hormones in
      improving cognitive function. The improvement in cognitive function with hormones
      is subtle and often not measurable on standard neuropsychological batteries.
      Patients have reported memory improvements in both declarative and procedural
      domains after being on hormonal replacement. Functional changes and vascular
      changes can be detected after hormonal replacement with more sophisticated
      imaging of the brain like PET scans. We hypothesize androgens and perhaps
      selective androgen receptor modulators as future treatment options for MCI in
      aging males.

PMID- 14728999
TI  - Is mania caused by overactivity of central brain-derived neurotrophic factor?
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor
      family, can modulate synaptic plasticity and neurotransmitter release across
      multiple neurotransmitter systems, as well as the intracellular signal
      transduction pathway. Recent studies had demonstrated that BDNF may play a role
      in the antidepressant mechanism and the pathogenesis of major depression. These
      findings implicated that BDNF may involve in mood regulation. In addition, (1).
      studies found positive association between BDNF genetic polymorphism and bipolar
      affective disorders; (2). agents which potentially induce manic states also
      increase BDNF, and (3). increase in mossy fibers were noted for bipolar affective
      disorder brain and BDNF is related to the induction of aberrant mossy fiber
      sprouting. From these finding, it is proposed that BDNF overactivity may be
      implicated in the manic state. The notion of BDNF overactivity in mania suggests
      that factors associated with increased BDNF activity may proffer the etiological
      fundamentals for bipolar affective disorder. Further, exploration of this
      hypothesis can provide a new direction in the treatment of the bipolar affective
      disorder.

PMID- 14729000
TI  - Schizophrenia, dissociative anaesthesia and near-death experience; three events
      meeting at the NMDA receptor.
AB  - The three events, viz. schizophrenia, dissociative anaesthesia and Near-Death
      Experience, despite their seemingly unrelated manifestation to each other, have
      nevertheless similar functional basis. All three events are linked to the
      glutamate sensitive N-methyl-D-aspartate (NMDA) receptor complex, which serves as
      their common functional denominator. Arguments and speculations are presented in
      favor of the view that, the three events might be considered as functional models
      of each other. Antagonism to the recognition NMDA-site of the receptor induces
      dissociative anaesthesia and precipitates Near-Death Experience. Agonist
      reinforcement at the modulatory glycine-site of the receptor counteracts negative
      symptoms of schizophrenia. Both types of challenges towards the receptor are
      compatible with a glutamate deficiency concept which underlies the meeting of the
      three events at the NMDA receptor.

PMID- 14729001
TI  - Schizophrenia and eye movement -- a new diagnostic and therapeutic concept.
AB  - In the present article, conclusions are drawn from four papers on the genesis of
      schizophrenia, published in Medical Hypotheses between 1999 and 2002, knowledge
      of which is required to understand this paper in greater depth. For these, the
      author had developed two sight tests in which schizophrenic patients revealed a
      stronger fusional reactivity of the nasal than of the temporal foveal halves and
      a disconnection between peripheral and foveal vision. Both phenomena could be
      explained by a reversed crossing of foveal projections in the chiasma opticum
      constituting a genetic vulnerability which, in case of additional defects of
      binocular balance, could result in a foveal convergence stimulus being executed
      as a divergence movement by one of the eyes. The author has now succeeded in
      finding a very simple standardized method to discover the described vergence
      abnormality, the Hook test, part of the ZEISS Near Pola Test, which would
      therefore be suitable for detecting schizophrenic vulnerability in screening
      tests so that the outbreak of schizophrenia could be prevented by an early
      correction of the additional visual defects. The movement impulses resulting from
      the erraneous vergence are analyzed and explain the phenomenon of the
      schizophrenic's "mad look". The connection between the somatic component and the
      patient's psycho-social problems is shown and a detailed description given of non
      neuroleptic methods of rectifying both.

PMID- 14729002
TI  - Down syndrome and epilepsy: a nutritional connection?
AB  - Non-Asian individuals with Down syndrome are much more likely to develop
      epileptic seizure disorders than individuals without Down syndrome. Examination
      of nutrient and metabolite levels in patients with these two seemingly disparate
      disorders reveals numerous similarities. Compared to individuals without these
      disorders, individuals with Down syndrome and individuals with seizures may have
      lower levels of vitamin A, vitamin B1, folate, vitamin B12, vitamin C, magnesium,
      manganese, selenium, zinc, carnitine, carnosine, choline, and possibly serine.
      Excesses of copper, cysteine, phenylalanine, and superoxide dismutase are also
      sometimes encountered in both disorders. In addition to common nutritional lower
      levels and excesses, disorders of metabolism involving vitamin B6, vitamin D,
      calcium, and tryptophan may play a common role. This paper hypothesizes that
      nutritional factors may account for the high joint occurrence of these
      conditions. Further examination of these data may provide insights into
      nutritional, metabolic and pharmacological treatments for both conditions.

PMID- 14729003
TI  - Is benign cough headache caused by intraocular haemodynamic aberration?
AB  - Rise of intracranial pressure (ICP) is currently presumed to underlie benign
      cough headache (BCH). Cough normally increases ICP but very few patients develop
      BCH. Children, young adults and females are rarely affected. Reduction of ICP by
      lumbar puncture (LP) or indomethacin offers variable therapeutic success. BCH can
      persist for several months or years but LP lowers ICP for few hours only and has
      significant morbidity. Choroidal blood volume and intraocular pressure (IOP) are
      instantaneously responsive to cough. Mechanical deformation of pressure-sensitive
      ocular structures by sudden experimental IOP elevation generates transient neural
      traffic in ocular trigeminal nerve fibres. Homeostatic mechanisms normally limit
      effect of cough-induced intraocular venous congestion. I propose that in a few
      patients, ocular sympathetic hypofunction significantly alters intraocular
      pressure-volume relation and predisposes to exaggerated choroidal venous
      congestion and fluctuation of IOP in response to cough, that, in turn, results in
      sudden transient cephalalgogenic antidromic trigeminal nerve discharge. Known
      variations in ocular hydrodynamics, ocular rigidity, and forced expiration
      rationalize epidemiology of BCH. This hypothesis can be tested by study of
      pupillary function and facial sweating in patients with BCH.

PMID- 14729004
TI  - Do hyporesponsive genetic variants of the melanocortin 1 receptor contribute to
      the etiology of multiple sclerosis?
AB  - Hyporesponsive genetic variants of the melanocortin 1 receptor result in
      pigmentary phenotypes exhibiting light skin and light color hair, including red
      hair. These variants are common in populations with high rates of multiple
      sclerosis, while rare in populations with low rates. Alpha-melanocyte stimulating
      hormone, the major ligand for this receptor, is responsible for phenotype
      determination, but is also known for its anti-inflammatory and immune modulating
      effects, including inhibition of factors implicated in multiple sclerosis
      pathology. As the melanocortin 1 receptor is expressed on various cell types
      involved in immune response, it is possible that carriers of hyporesponsive
      variants of this receptor lack the full anti-inflammatory and immune modulating
      effects of alpha-melanocyte stimulating hormone. It is proposed that these
      variants are part of a spectrum of genes involved in the etiology of multiple
      sclerosis. Related aspects of multiple sclerosis epidemiology are examined.

PMID- 14729005
TI  - Does a single time function adequately describe blood glucose concentration
      dynamics during an OGTT?
AB  - The Oral Glucose Tolerance Test is a commonly used test for diagnosis of Impaired
      Glucose Tolerance and Type 2 Diabetes Mellitus. In practice, there are two
      standard sample time intervals: deltat=60 min and deltat=30 min and two standard
      test time durations: 120 and 180 min. However, for an accurate description of
      blood glucose concentration dynamics, this number of samples is not enough. In
      the present work, test duration is considered beyond 180 min and a shorter time
      interval of deltat=10 min is proposed. Two main hypotheses are discussed: (a).
      Blood glucose concentration dynamics can be viewed as the impulse response of a
      "black box" system where the output is conformed by the algebraic sum of a set of
      exponentially damped sinusoidal functions and (b). There exists at least one
      endogenous excitation that acts as a counterregulatory mechanism against
      hypoglycemic tendencies.

PMID- 14729006
TI  - A shift in myocardial substrate, improved endothelial function, and diminished
      sympathetic activity may contribute to the anti-anginal impact of very-low-fat
      diets.
AB  - A new category of anti-anginal drug - exemplified by ranolazine - is believed to
      work by partially inhibiting cardiac oxidation of fatty acids; oxidation of
      glucose requires less oxygen per mol of ATP generated, and thus is preferable to
      fat oxidation when oxygen availability is limiting in underperfused cardiac
      tissue. Unfortunately, there is no reason to believe that these drugs inhibit fat
      oxidation selectively in the heart; thus, chronic use of these drugs can be
      expected to increase body fat stores until the original rate of fat oxidation is
      restored by mass action - presumably negating the therapeutic benefit in angina,
      while exacerbating the manifold adverse effects of insulin resistance syndrome.
      The rational way to decrease cardiac metabolic reliance on fatty acids is to
      consume a very-low-fat quasi-vegan diet (i.e., 10% fat calories). Indeed, such
      diets are known to have a rapid and substantial therapeutic impact on anginal
      symptoms, while concurrently benefiting insulin sensitivity, markedly improving
      serum lipid profile, promoting leanness, and lessening coronary risk. A reduction
      in diurnal insulin secretion might also be achieved, which would be expected to
      decrease sympathetic activity. While reduced myocardial demand for oxygen
      doubtless contributes to the beneficial impact of such diets on angina, it is
      likely that improved cardiac perfusion consequent to improved endothelium
      dependent vasodilation also plays a role in this regard. Supplemental carnitine,
      also beneficial in angina, appears to improve utilization of glucose in the
      ischemic myocardium by lowering elevated acetyl-coA levels and thereby
      disinhibiting pyruvate dehydrogenase. Certain other nutraceuticals may aid
      control of angina by improving endothelial function. In the longer term, these
      measures have the potential to slow or reverse the progression of stenotic
      lesions that underlie most cases of angina. These safe and relatively inexpensive
      nutritional strategies for coping with angina deserve far more attention than
      orthodox medical practice has thus far accorded them.

PMID- 14729007
TI  - Hypothetical hypercholesterolaemia and atherosclerosis.
AB  - Recent pathological advances in experimental and iatrogenic atherosclerosis and
      critical review of the epidemiology of coronary heart disease revealed fallacious
      data and methodological errors underlying the hypercholesterolaemia/lipid
      hypothesis. Misuse of risk factors, inappropriate use of surrogates and
      misinterpretation of data pertaining to cholesterol's role in atherogenesis
      necessitate greater precision in word usage and terminology, reinstitution of the
      statistical reference range for cholesterol and closer scientific surveillance of
      aetiological endeavours in medicine.

PMID- 14729008
TI  - Portal hypertension: return to fetal life to re-attempt differentiation?
AB  - We speculate on the final meaning of the alterations that characterize portal
      hypertensive enteropathy. The similarity of these alterations with certain
      morphofunctional characteristics of prenatal splanchnic development makes it
      possible to hypothesize that the dedifferentiation with return to early stages of
      development could constitute a portal hypertension induced pathogenic mechanism.

PMID- 14729009
TI  - Hyperdynamic circulation in liver cirrhosis: desensitization of vasoconstrictive
      receptors by G protein-coupled receptor kinases.
AB  - Liver cirrhosis is complicated by a hyperdynamic circulation characterized by a
      generalized arterial vasodilatation. This vasodilatation occurs despite high
      plasma concentration of several potent vasoconstrictive substances like
      angiotensin, vasopressin, endothelin and norepinephrine. The experimental
      evidence available shows that compensatory adrenergic and vasoconstrictive
      signals are not normally transmitted intracellularly. G protein-coupled receptor
      kinases phosporylate plasma membrane receptors and block the transmission of the
      signal intracellularly. We hypothesize that these kinases are responsible for the
      desensitization to vasoconstrictors observed in patients with liver cirrhosis.
      Pharmacological intervention at this level might be beneficial to treat
      complications like ascites and variceal bleeding.

PMID- 14729010
TI  - The role of psychosocial factors in the progression of hepatocellular carcinoma.
AB  - The number of deaths per year from hepatocellular carcinoma (HCC) exceeds 250000,
      placing it sixth as the cause of death from cancer worldwide. The primary
      etiology of most cases of HCC in the US is hepatitis B and/or C. Extensive
      research has demonstrated that the relationship between hepatitis B infection and
      the progression to HCC is mediated by the immune system. A substantial, but
      unrelated literature, describes the relationship between psychosocial factors
      (e.g., stress, psychiatric morbidity), immune system reactivity, and disease
      progression in patients with cancer. However, the role of these factors in the
      progression of HBV-HCC has not been explored. An understanding of the
      relationship among virology, immunology, and behavior in the development and
      recurrence of HCC may provide alternative methods for secondary prevention of HCC
      (e.g., behavioral) until a vaccine and/or pharmacological treatments are
      developed, feasible, and affordable.

PMID- 14729011
TI  - Is the host responsible? -- the role of the immune system in Helicobacter pylori
      infection.
AB  - Helicobacter pylori is the primary aetiological agent of chronic gastritis and a
      necessary factor in most peptic ulcer disease. To date the majority of studies,
      which have examined factors predictive of disease outcome, have concentrated on
      bacterial virulence factors. Recent evidence suggests that the immune response
      might be responsible. Fc receptors polymorphisms have been implicated in
      autoimmune diseases and persistent bacterial infections. Individuals who are H.
      pylori positive and homozygous recessive for the FcgammaRIIa receptor may have a
      higher risk of developing peptic ulcer disease rather than gastritis.

PMID- 14729012
TI  - Cellular formation of DNA and RNA and the relationship to tumour cell
      development.
AB  - A hypothesis concerning the mode of formation of the components of DNA and RNA in
      living cells is described. This is based on the reversible hydration and
      dehydration of polyphosphoric acids in the cell. It is shown that formation of
      DNA in the cell directs reacting chemicals from the outer membrane of the cell
      towards the centre leading to the conclusion that all cells operate in the same
      manner. Cell products are therefore a function of the nature and concentration of
      chemicals in the source of supply. The origin of tumour cells is proposed as the
      formation of distorted nuclei. Suggestions are advanced as to means of correcting
      this situation.

PMID- 14729013
TI  - Ketocazole as an adjunct to finasteride in the treatment of androgenetic alopecia
      in men.
AB  - Dihydrotestosterone (DHT) binding to androgen receptors (AR) in hair follicles is
      commonly accepted as the first step leading to the miniaturizing of follicles
      associated with androgenetic alopecia (AGA). Testosterone is converted to DHT by
      the enzyme 5alpha-reductase. Finasateride a 5alpha-reducase inhibitor blocks the
      production of DHT and is currently used to treat AGA. The inhibition is not
      complete but a reduction of DHT systemically and in the scalp is accomplished.
      Ketoconazole has been clinically shown to be effective in the treatment of AGA.
      In this paper, evidence is presented to support the hypothesis that ketoconazole
      2% shampoo has a local disruption of the DHT pathway. It is proposed that using
      ketoconazole 2% shampoo as an adjunct to finasteride treatment could lead to a
      more complete inhibition of DHT and thus better treat AGA.

PMID- 14729014
TI  - The clinical advantages of cold-pressed non-raffinated evening primrose oil over
      refined preparations.
AB  - The non-triglyceride fraction of unrefined evening primrose oil has recently been
      shown to contain 3-O-trans-caffeoyl derivatives of betulinic, morolic, and
      oleanolic acid. These lipophilic pentacyclic triterpenes have free radical
      scavenging, cyclooxygenase and neutrophil elastase inhibitory activities, and are
      therefore likely to be of benefit to human health. However, biochemical assays
      have suggested that these lipophilic antioxidants only occur in trace amounts, if
      at all, in commercial samples of evening primrose oil. A newly available
      commercially available cold-pressed, non-raffinated evening primrose oil
      preparation was found to contain a pentacyclic triterpene ester. Given the
      potential benefits of the triterpene esters, it is suggested that such a cold
      pressed, non-raffinated commercially available evening primrose oil product is
      likely to have greater health benefits than conventional evening primrose oil
      preparations.

PMID- 14729015
TI  - A biomechanical basis for the prescription of orthoses in the treatment of common
      running injuries.
AB  - Orthoses are beneficial in the treatment of common running injuries. They limit
      abnormal pronation and reduce injurious torque to the musculotendinous structures
      of the leg and knee. Recent kinematic research has disputed this mechanism. An
      alternative model is proposed.

PMID- 14729016
TI  - Otosclerosis is a conformational disease.
AB  - The otosclerotic focus is a result of the normal process of bone remodelling in
      the otic capsule - a place where there is little if any bone remodelling. There
      is still no single accepted theory for the pathogenesis of otosclerosis. Sources
      we used were relevant clinical and basic science publications from 1973 to 2001.
      The data from each publication were critically reviewed. In this paper we suggest
      a kind of molecular predisposition in otosclerosis, like molecular instability in
      some key protein with regulatory effect, cell receptor for example. Also it can
      be a destabilasing mutation of some repressor of the normal bone remodelling. Any
      triggering event like mechanic distress, vascular compromise, radiation, viral
      infection, etc. can start a process of conformational changes with subsequent
      induction of long-standing bone remodelling focuses. We conclude that many
      unusual features of otosclerosis can be explained if we consider this entity as a
      conformational disease.

PMID- 14729017
TI  - A hypothesis on the role of the electrical charge of haemoglobin in regulating
      the erythrocyte shape.
AB  - A previously proposed mechanism of erythrocyte shape has been proposed in which
      the ratio of the two conformations of Band 3, the anion exchange protein,
      controls the erythrocyte shape by modifying the degree of contraction or
      relaxation of the membrane skeleton. This mechanism was previously shown to
      explain several observations related and unrelated to the erythrocyte shape. We
      show that it can also explain the occurrence of target cells in blood smears of
      individuals expressing Hb A variants with significantly lower and higher
      isoelectric points. This would provide further support of its validity and would
      have the following implications. The electrical charge of of Hb A influences the
      erythrocyte shape and deformability, thus explaining the low level of expression
      of Hb A2 with an isoelectric point significantly higher than Hb A. It would
      suggest that Hb A2 has a physiological function related to the control of the
      erythrocyte shape. This could be of regulating the activity of the K-Cl
      cotransport system or of tuning finely the cell pH. A role of haemoglobin in the
      control of the erythrocyte shape would ensure a more efficient oxygenation of
      tissues and removal of carbon dioxide generated by tissues. It would also provide
      a basis for the absence of spreading in populations of some haemoglobin variants
      differing only by the electrical charge.

PMID- 14729018
TI  - Pre-menstrual syndrome: a new concept in its pathogenesis and treatment.
AB  - It is proposed that the normal regulation of the vasodilatation and vascular
      lengthening during the luteal phase of the menstrual cycle is due to the
      increased release of endothelial nitric oxide as a result of the maximum
      oestrogen/progesterone levels as manifest during this phase. Excessive levels of
      NO have additional systemic effects, and these may present as the pre-menstrual
      syndrome which classically occurs during the luteal phase of the menstrual cycle.
      The manufacture of NO is under the control of the enzyme NO synthase. The
      concentration of the latter can be affected by steroids. The proposed new
      treatment of PMS is premised on the basis that oral steroids given during the
      luteal phase will reduce the levels of NO and thus in turn will miminise the
      signs and symptoms of PMS.

PMID- 14729019
TI  - Estrogen: one of the risk factors in milk for prostate cancer.
AB  - Studies to elucidate the cause of prostate cancer have met with little success to
      date. Epidemiological studies suggested that milk consumption is probably as one
      of the risk factors for prostate cancer. The studies thus focused on the fat and
      calcium in milk, but reached no definitive conclusion. According to the
      measurements of estrogen levels in milk by different studies, it was suggested
      that estrogen in milk was a possible risk to cause prostate cancer. One reason
      supporting this hypothesis is that Western diet (characterized by milk/dairy
      products and meat) causes a trend of increasing levels of estrogens, and Western
      males show a higher incidence rate of prostate cancer than Asia males. Estrogen
      levels in prostate fluid are also correlated very well with the prostate cancer.
      During several decades, estrogens, together with testosterone, was commonly used
      to induce the rodent model of prostate cancer. Our hypothesis also was supported
      by the presence of estrogen receptors in the prostate gland and the genotoxic
      role of estrogens on the prostate gland, as possible mechanisms. Therefore, if
      modern milk consumption does expose consumers to high levels of estrogen and
      plays an adverse role in prostate cancer, action should be taken to produce the
      noncontaminant milk.

PMID- 14729020
TI  - Fetal sensitivity to testosterone, left-handedness and development of bronchial
      asthma: a new approach.
AB  - In contrast to Geschwind, Behan and Galaburda (GBG) theory, there is strong
      evidence that inheritance through maternal line is responsible for the
      coexistence of asthma and left-handedness early in childhood. A new model that
      incorporates GBG's theory and maternal inheritance is proposed. This hypothesis
      suggests that maternal atopy is the most important factor in the evolution of
      asthma and that GBG's theory applies mainly in childhood. An inherited enhanced
      sensitivity of fetus to testosterone may be the underlying mechanism that leads
      to the development of bronchial asthma.

PMID- 14729021
TI  - Hypothesis: epididymis inhibits sperm motility inside male reproductive tract.
AB  - Epididymis (ES) inhibits the total activities of spermatozoa (SA) in male
      reproductive tract. It keeps SA motionless throughout the length of system by its
      inhibitory factors (IFs), which are nullified by the secretary products of other
      glands after formation of semen externally.

PMID- 14729022
TI  - Tying it all together: telomeres, sexual size dimorphism and the gender gap in
      life expectancy.
AB  - The classic explanation that women outlive men solely due to hormonal and
      lifestyle differences, does not withstand a critical analysis. In developed
      countries, the average gap in life expectancy between the sexes is 7 years. It
      has widened over the last decades, despite the trend of women copying the
      'unhealthy' lifestyle of men. Estrogen levels in postmenopausal women are
      virtually identical to estrogen levels in males and can hardly explain the
      discrepancy. Furthermore, testosterone got its bad reputation from one study on
      mentally retarded men, which has to be interpreted with caution. However, sexual
      size dimorphism with men being the larger sex in conjunction with the limited
      replication potential of human somatic cells might account for higher mortality
      rates in males, especially at old age. The hypothesis, as presented here, is
      based on the well-known concept of a cellular mitotic clock, which was discovered
      by Leonard Hayflick almost half a century ago. The underlying counting mechanism,
      namely the gradual erosion of chromosome ends (telomeres) due to the end
      replication problem of linear DNA molecules, was first described by Alexey
      Olovnikov in 1971 and with minor modifications has become a widely accepted
      paradigm. In a recent Lancet study, an inverse correlation between mean telomere
      length and mortality in people has been found. In this and two other studies, it
      was confirmed that males do have shorter telomeres than females at the same age.
      This is almost certainly a consequence of men being usually taller than women,
      although nobody has done an investigation yet. Clearly, a larger body requires
      more cell doublings, especially due to the ongoing regeneration of tissues over a
      lifetime. Accordingly, the replicative history of male cells might be longer than
      that of female cells, resulting in the exhaustion of the regeneration potential
      and the early onset of age-associated diseases predominantly in large-bodied
      males. Inherited telomere length variation between unrelated individuals might
      have obscured a clear correlation between body height and mortality, leading to
      conflicting results in some studies. Finally, I propose that the secular height
      increase over the last decades, of about 2.5 cm per generation in the western
      world, has to be blamed for the widening of the gender gap in life expectancy.

PMID- 14729023
TI  - Anthrax and the etiology of the English sweating sickness.
AB  - In 2001, spores of Bacillus anthracis were deliberately sent through the United
      States postal system, resulting in five deaths from inhalational anthrax. Rarely
      observed clinical symptoms associated with these cases led to a hypothesis about
      the etiology of the English Sweating Sickness. The disease appeared sporadically
      in England between 1485 and 1551. Numerous viruses have been proposed as possible
      causes of the "English Sweat". Anthrax has not previously been considered
      because, documented cases of inhalational anthrax have been rare and pronounced
      sweating was not a noted symptom of the more common cutaneous and
      gastrointestinal forms of anthrax. Victims of the English Sweating Sickness have
      recently been identified in undisturbed tombs. It may be possible to examine
      those bodies and coffins for the presence of resilient anthrax spores and DNA
      using modern genomic tools.

PMID- 14729024
TI  - Electro-convulsive therapy, nitric oxide and HPA axis: a closer look at human
      hypothalamus.

PMID- 14729025
TI  - Quantitative high-resolution on-line NMR spectroscopy in reaction and process
      monitoring.
AB  - On-line nuclear magnetic resonance spectroscopy (on-line NMR) is a powerful
      technique for reaction and process monitoring. Different set-ups for direct
      coupling of reaction and separation equipment with on-line NMR spectroscopy are
      described. NMR spectroscopy can be used to obtain both qualitative and
      quantitative information from complex reacting multicomponent mixtures for
      equilibrium or reaction kinetic studies. Commercial NMR probes can be used at
      pressures up to 35 MPa and temperatures up to 400 K. Applications are presented
      for studies of equilibria and kinetics of complex formaldehyde-containing
      mixtures as well as homogeneously and heterogeneously catalyzed esterification
      kinetics. Direct coupling of a thin-film evaporator is described as an example
      for the benefits of on-line NMR spectroscopy in process monitoring.

PMID- 14729026
TI  - A simple method for NMR photography.
AB  - The application of a multi-frequency weak pulse to a liquid crystal can excite
      narrow 1H NMR peaks at the applied frequencies. By using two-level amplitude
      coding, namely setting the amplitudes of some of the harmonics to zero, this
      method can be used to store up to 1024 bits of binary information in the liquid
      crystal molecules. When the information is retrieved in the form of a spectrum,
      which is plotted as an array of 32 or 16 segments, the stack of spectral segments
      reproduces a 2D input pattern quite well. This technique is called "NMR
      photography." The original method was a pseudo-2D technique that applies the 1024
      frequency pulse in the first step, and reads the signal row-by-row in the second
      step. The present improvement involves subtracting two spectra obtained with the
      same 1024-frequency pulse but with different durations, so that the method
      becomes a 1D technique, with a tremendous saving of experimental time. Several
      examples are given to illustrate the results.

PMID- 14729027
TI  - Line shape considerations in ultrafast 2D NMR.
AB  - We have recently proposed and demonstrated an approach that enables the
      acquisition of 2D nuclear magnetic resonance (NMR) spectra within a single scan.
      The approach is based on spatially encoding the spins' evolution along the
      indirect domain with the aid of a magnetic field gradient, and subsequently
      decoding this information numerous times over the course of the signal
      acquisition while spins are subject to a train of gradient echoes. The present
      paper discusses further considerations pertaining the 2D line shapes arising from
      this new way of collecting NMR data. Specific issues that are hereby addressed
      include (i) the effects introduced by fast relaxation onto the spatial encoding
      process, particularly the line widths and line shapes that will then arise in the
      frequency domain; (ii) approaches capable of correcting for the mixed-phase
      kernels resulting in these fast-relaxation cases, corresponding in essence to
      spatially encoded analogs of the TPPI and hypercomplex time-domain acquisition
      procedures; (iii) the enveloping characteristics imposed by the use of discrete
      excitation pulses on the attainable spectral widths along the indirect domain;
      and (iv) an analysis of the signal-to-noise characteristics of the methodology,
      with experimental corroborations of theoretical predictions and an illustration
      of the method's capabilities to analyze protein solutions in the mM-range
      concentration.

PMID- 14729028
TI  - Background gradient suppression in stimulated echo NMR diffusion studies using
      magic pulsed field gradient ratios.
AB  - By evaluating the spin echo attenuation for a generalized 13-interval PFG NMR
      sequence consisting of pulsed field gradients with four different effective
      intensities (F(p/r) and G(p/r)), magic pulsed field gradient (MPFG) ratios for
      the prepare (G(p)/F(p)) and the read (G(r)/F(r)) interval are derived, which
      suppress the cross term between background field gradients and the pulsed field
      gradients even in the cases where the background field gradients may change
      during the z-store interval of the pulse sequence. These MPFG ratios depend only
      on the timing of the pulsed gradients in the pulse sequence and allow a
      convenient experimental approach to background gradient suppression in NMR
      diffusion studies with heterogeneous systems, where the local properties of the
      (internal) background gradients are often unknown. If the pulsed field gradients
      are centered in the tau-intervals between the pi and pi/2 rf pulses, these two
      MPFG ratios coincide to eta=G(p/r)/F(p/r)=1-8/[1+(1/3)(delta/tau)(2)]. Since the
      width of the pulsed field gradients (delta) is bounded by 0< or =delta< or =tau,
      eta can only be in the range of 5< or =-eta< or =7. The predicted suppression of
      the unwanted cross terms is demonstrated experimentally using time-dependent
      external gradients which are controlled in the NMR experiment as well as
      spatially dependent internal background gradients generated by the magnetic
      properties of the sample itself. The theoretical and experimental results confirm
      and extend the approach of Sun et al. (J. Magn. Reson. 161 (2003) 168), who
      recently introduced a 13-interval type PFG NMR sequence with two asymmetric
      pulsed magnetic field gradients suitable to suppress unwanted cross terms with
      spatially dependent background field gradients.

PMID- 14729029
TI  - Rational reduction of periodic propagators for off-period observations.
AB  - Many common solid-state nuclear magnetic resonance problems take advantage of the
      periodicity of the underlying Hamiltonian to simplify the computation of an
      observation. Most of the time-domain methods used, however, require the time step
      between observations to be some integer or reciprocal-integer multiple of the
      period, thereby restricting the observation bandwidth. Calculations of off-period
      observations are usually reduced to brute force direct methods resulting in many
      demanding matrix multiplications. For large spin systems, the matrix
      multiplication becomes the limiting step. A simple method that can dramatically
      reduce the number of matrix multiplications required to calculate the time
      evolution when the observation time step is some rational fraction of the period
      of the Hamiltonian is presented. The algorithm implements two different
      optimization routines. One uses pattern matching and additional memory storage,
      while the other recursively generates the propagators via time shifting. The net
      result is a significant speed improvement for some types of time-domain
      calculations.

PMID- 14729030
TI  - MRI technique for measurement of velocity vectors, acceleration, and
      autocorrelation functions in turbulent flow.
AB  - In this paper, we show velocity images for liquid flow in a cylindrical pipe at
      Reynolds numbers of up to 5000. Three orthogonal velocity components are acquired
      from a single excitation over a timescale of 60 ms thus obtaining an
      'instantaneous' description of the fluid flow in steady laminar and chaotic
      turbulent flow. It is also shown how the technique, termed the gradient echo
      rapid velocity and acceleration imaging sequence (GERVAIS), can be used to
      acquire acceleration (convective derivative) images by incorporation of double
      pulsed gradient spin echo (PGSE) pairs into the pulse sequence such that the
      resulting phase shift is a measure of the change in the velocity over the mixing
      time between successive PGSE pairs. The technique has also been used to acquire
      up to 16 successive z-velocity images, providing spatio-temporal information of
      the velocity fluctuations over a period of 320 ms, which are then used to
      calculate spatially resolved velocity autocorrelation functions. It is found that
      over the timescale of the velocity measurements, which is principally determined
      by the residence time in the coil, the local velocity fluctuations are seen to be
      small compared to the local velocities, confirming that the data acquisition
      times achieved are rapid enough to capture 'instantaneous' images of the flow
      field.

PMID- 14729031
TI  - Amide proton relaxation measurements employing a highly deuterated protein.
AB  - Proton NMR longitudinal and transverse relaxation rates of unlabelled proteins
      are generally dominated by the many 1H-1H dipolar interactions so that spin
      diffusion, rather than molecular or internal motions, governs longitudinal
      relaxation. Here, relaxation measurements of backbone amide proton (1H(N))
      magnetisations have been carried out employing the 99% 2H, 98% 15N labelled,
      small 2F2 protein domain in 10%/90% H(2)O/D(2)O solution. Under these conditions,
      the longitudinal relaxation rates exhibit time constants, T(1)*=1/R(1)* if
      described by a mono-exponential, within the range of 3.0 to 18.7s-a wide range
      which indicates that the phenomenon of spin diffusion has been greatly reduced.
      The majority of 1H(N) nuclei in this sample (pH 4.0 and 5 degrees C) exhibit
      chemical exchange with solvent that couples their longitudinal relaxation to that
      of the solvent. For the subset of 1H(N) nuclei not undergoing detectable solvent
      chemical exchange, the R(1)* rates correlate well with their individual
      1H(N,O)/2H(N,O) structural environments. The correlation for corresponding
      transverse relaxation rates, R(2)* was found to be less good. Longitudinal
      relaxation measurements in 1%/99% H(2)O/D(2)O solution identify a further subset
      of 1H(N) nuclei which exhibit essentially indistinguishable R(1)* rates in both
      1% and 10% H(2)O, implying that averaging of rates from spin diffusion processes
      and different 2F2 isotopomer populations are negligible for these 1H(N) sites. In
      addition to a high sensitivity to structural parameters, model calculations
      predict 1H(N) relaxation rates to exhibit pronounced sensitivity to internal
      dynamics.

PMID- 14729032
TI  - Measurement of dipole-dipole cross-correlated relaxation in fast rotating CH2D
      groups.
AB  - Studies of protein dynamics are key to understanding their biological function.
      NMR relaxation studies of proteins to date have focused primarily on
      characterizing backbone dynamics. In this paper, we focus on the aliphatic side
      chains (Ala, Thr, Val, Leu, and Ile) with the goal of deriving dynamical
      information on the motion of terminal methyl groups. Dipole-dipole cross
      correlated cross-relaxation is analyzed in a fast rotating CH(2)D group, as found
      in partially deuteriated proteins. In comparison with previous studies on AMX
      spin systems (methylene C(beta)H(2) groups), the fast rotation of the methyl
      group makes a number of relaxation pathways efficient, through the coherence
      C(+)H(1)(+)H(2)(-)+C(+)H(1)(-)H (2)(+). Several pulse schemes were designed to
      evaluate these relaxation rates: the measured values are small and well predicted
      by taking into account the complete relaxation network, but they remain strongly
      influenced by 1H-1H relaxation with all protons in the neighborhood of the CH(2)D
      moiety. The prospects and limitations of this method are discussed in comparison
      with 2H relaxation measurements.

PMID- 14729033
TI  - Effects of residual single-quantum coherences in intermolecular multiple-quantum
      coherence studies.
AB  - Intermolecular multiple-quantum coherences (iMQCs) have been reported to offer a
      sensitivity to sample structure at a specific user-defined length scale down to
      the order of 10 microm. When assessing this novel contrast mechanism in
      controlled phantom experiments, we have observed three different mechanisms
      whereby residual single-quantum coherences (SQCs) arising from intense high
      spatial frequencies, stimulated echoes and strong spatially encoding gradients
      can produce significant changes in signal contrast at particular length scales.
      These changes which only appear when components arising from SQCs and iMQCs are
      both present in the detected signal, are similar to changes previously attributed
      to iMQCs alone. We demonstrate each mechanism by which these residual SQCs arise
      and describe methods for their suppression.

PMID- 14729034
TI  - 3D imaging with a single-sided sensor: an open tomograph.
AB  - An open tomograph to image volume regions near the surface of large objects is
      described. The central achievement in getting such a tomograph to work is the
      design of a fast two-dimensional pure phase encoding imaging method to produce a
      cross-sectional image in the presence of highly inhomogeneous fields. The method
      takes advantage of the multi-echo acquisition in a Carr-Purcell-Meiboom-Gill
      (CPMG)-like sequence to significantly reduce the experimental time to obtain a 2D
      image or to spatially resolve relaxation times across the sensitive volume in a
      single imaging experiment. Depending on T(2) the imaging time can be reduced by a
      factor of up to two orders of magnitude compared to the one needed by the single
      echo imaging technique. The complete echo train decay has been also used to
      produce T(2) contrast in the images and to spatially resolve the T(2)
      distribution of an inhomogeneous object, showing that variations of structural
      properties like the cross-link density of rubber samples can be distinguished by
      this method. The sequence has been implemented on a single-sided sensor equipped
      with an optimized magnet geometry and a suitable gradient coil system that
      provides two perpendicular pulsed gradient fields. The static magnetic field
      defines flat planes of constant frequency parallel to the surface of the scanner
      that can be selected by retuning the probe frequency to achieve slice selection
      into the object. Combining the slice selection obtained under the presence of the
      static gradient of the open magnet with the two perpendicular pulsed gradient
      fields, 3D spatial resolution is obtained.

PMID- 14729035
TI  - AIR-SPAMM: alternative inversion recovery spatial modulation of magnetization for
      myocardial tagging.
AB  - Alternate inversion recovery spatial modulation of magnetization (AIR-SPAMM) can
      be used either for doubling the number of tags for a given tagging encoding
      gradient strength or for improving tagging contrast ratio. AIR-SPAMM requires
      only a single acquisition and utilizes inversion pulses spaced throughout the
      gradient recalled echo (GRE) cine acquisition to "lock" the recovering
      magnetization at a desired level. The theory of AIR-SPAMM is presented along with
      simulations and results from phantoms. AIR-SPAMM can be used either for imaging
      systole as demonstrated by initial in vivo results or potentially for imaging the
      entire cardiac cycle in a slice-interleaved manner.

PMID- 14729036
TI  - Direct EPR detection of transient and continuous wave signals at 2.5 GHz.
AB  - Direct detection of free induction decays and electron spin echoes, and the
      recording of echo-detected EPR spectra and electron spin echo envelope modulation
      patterns at a microwave frequency of 2.5 GHz is demonstrated. This corresponds to
      the measurement of the transverse magnetization in the laboratory frame, rather
      than in the rotating frame as usually done by down-converting the signal
      (homodyne detection). An oscilloscope with a 6-GHz analog bandwidth, a sampling
      rate of 20 GigaSamples per second, and a trigger frequency of 5 GHz for the edge
      trigger and 750 MHz for the advanced trigger, is used in these experiments. For
      signal averaging a 3-GHz microwave clock divider has been developed to
      synchronize the oscilloscope with the frequency of the EPR signal. Moreover,
      direct detection of continuous wave EPR signals at 2.5 GHz is described.

PMID- 14729037
TI  - Magnetic resonance elastography and diffusion-weighted imaging of the sol/gel
      phase transition in agarose.
AB  - The dynamics of the sol/gel phase transition in agarose was analyzed with
      magnetic resonance elastography (MRE) and diffusion-weighted imaging, providing
      complementary information on a microstructural as well as on a macroscopic
      spatial scale. In thermal equilibrium, the diffusion coefficient of agarose is
      linearly correlated with temperature, independent of the sol/gel phase
      transition. In larger agarose samples, the transition from the sol to the gel
      state was characterized by a complex position and temperature dependency of both
      MRE shear wave patterns and apparent diffusion coefficients (ADC). The position
      dependency of the temperature was experimentally found to be qualitatively
      similar to the behavior of the ADC maps. The dynamics of the temperature could be
      described with a simplified model that described the heat exchange between sol
      and gel compartments. The experiments supported the approach to derive
      temperature maps from the ADC maps by a linear relationship. The spatially
      resolved dynamics of the temperature maps were therefore employed to determine
      the elasticities. For this reason, experimental MRE data were simulated using a
      model of coupled harmonic oscillators. The calculated images agreed well with the
      experimentally observed MRE wave patterns.

PMID- 14729038
TI  - A solid-state 14N magic-angle spinning NMR study of some amino acids.
AB  - Experimental strategies for the acquisition of high-quality 14N magic-angle
      spinning (MAS) NMR spectra of the simple amino acids, which exhibit 14N
      quadrupole coupling constants (C(Q)) on the order of 1.2 MHz, are devised. These
      are the first useful 14N MAS spectra reported for nitrogen compounds having a
      C(Q)(14N) value in excess of 1 MHz. The complete manifolds of spinning sidebands
      (ssbs), i.e., about 300 ssbs for a spinning frequency of 6.0 kHz, have been
      observed in the 14N MAS NMR spectra of a series of amino acids. In their crystal
      structure these amino acids all exhibit the zwitterionic form and thus the 14N
      MAS NMR spectra represent those of a rotating -NH(3)(+) group and not of an amino
      (-NH(2)) group. Computer simulations combined with fitting of simulated to the
      experimental ssb intensities result in the determination of precise values for
      the 14N quadrupole coupling (C(Q)) and its associated asymmetry parameter
      (eta(Q)) for the nitrogen sites in these molecules. For some of the amino acids
      the 14N MAS NMR spectra exhibit overlap between the manifolds of ssbs from two
      different nitrogen sites in accordance with their crystal structures. Computer
      analysis of these spectra results in two different sets of (C(Q), eta(Q)) values
      which mainly differ in the magnitudes for eta(Q).

PMID- 14729039
TI  - Constant time steady gradient NMR diffusometry using the secondary stimulated
      echo.
AB  - A pulse sequence producing a second stimulated echo is suggested for the
      compensation of relaxation and residual dipolar interaction effects in steady
      gradient spin echo diffusometry. Steady field gradients of considerable strength
      exist in the fringe field of NMR magnets, for instance. While the absolute echo
      time of the second stimulated echo is kept constant throughout the experiment,
      the interval between the first two radiofrequency pulses is augmented leading to
      a modulation of the amplitude of that second stimulated echo by self-diffusion
      only. The unique feature of this technique is that it is of a single-scan/single
      echo-signal nature. That is, no reference signals neither of the same pulse
      sequence nor of separate experiments are needed. The new method was tested with
      poly(ethylene oxide) melts and proved to provide reliable data for (time
      dependent) self-diffusion coefficients down to the physical limit (D
      approximately 10(-15)m(2)/s) when flip-flop spin diffusion starts to become
      effective.

PMID- 14729041
TI  - The time of palatal fusion in mice: a factor of strain susceptibility to
      teratogens.
AB  - Induction of facial clefts in an animal model is often performed in experimental
      teratology. The susceptibility to teratogens of different strains of mice is
      genetically determined and seems to depend on the time of palatal fusion during
      embryogenesis. In order to elucidate the mode of action of preventive measures,
      we determined the exact time of palatal fusion in different strains of mice used
      for experiments in our laboratory. Fusion of the secondary palate is finished in
      the Halle: NMRI-mice at day 15, 0 h of gestation, in Halle: DBA and in A/WySnJ
      mice at day 15, 6 h and in the Halle: Jena AB-mice at day 15, 12 h. This sequence
      is at variance with spontaneous cleft rates and susceptibility to teratogens.

PMID- 14729042
TI  - Cranioplasty using acrylic material: a new technical procedure.
AB  - AIM: Today, cranioplasty is performed using different procedures. Numerous
      materials may be used to reconstruct the cranial vault including autologous bone
      and different types of synthetic resins. When plastic materials are used, the
      main requirement for an effective cranioplasty is the preoperative shaping of the
      implant to fit the bony defect precisely. In this paper, experience with a new
      method for cranioplasty using an acrylic cranial implant is presented. MATERIAL
      AND METHODS: In this new technical procedure an acrylic implant, precisely shaped
      to the defect, is fabricated preoperatively using CT data. The study consists of
      15 cases in whom cranioplasty was performed using this method. In all these,
      reconstruction was at least 3 months after the initial operation that lead to the
      cranial bony defect. RESULTS: No major complications occurred and the final
      functional and aesthetic results were good in all cases. The acrylic implant
      manufacture does not require the use of complex computer interface software or
      high-tech equipment, but involves simple, cheap, repeatable processes.

PMID- 14729043
TI  - Treatment of monostotic fibrous dysplasia with pamidronate.
AB  - INTRODUCTION: Fibrous dysplasia is a condition where fibrous tissue and bone with
      an altered structure replace normal bone. The craniofacial involvement is
      difficult to treat due to location, uncontrolled proliferation and compression of
      nerves. These result in facial asymmetry, pain, cranial nerve deficiencies, loss
      of vision or hearing, alterations in breathing, etc. The use of pamidronate,
      which inhibits the resorptive activity of osteoclasts may be an alternative to
      surgical intervention and may improve the results of treatment. AIM OF STUDY: To
      evaluate the treatment of monostotic craniofacial fibrous dysplasia with
      pamidronate. MATERIAL: A prospective pilot study was undertaken in 6 children
      with progressive fibrous dysplasia located in the mandible (3 pts), maxilla (2
      pts) or cranial base (1 pt). Surgery consisted only of a biopsy and implantation
      of gentamycin sponge into the biopsy bed in 3 cases in which an infection was
      initially suspected. All patients received pamidronate infusions (1mg/kg i.v. for
      3 days, every 4-6 months). The changes in bone density and extension of the
      disease were evaluated by serial orthopantomograms and CT scans. Follow up time
      was 9-24 months. RESULTS: Pain relief was achieved in all cases, decrease in
      swelling in 3, and stabilization in 3 cases. Radiological investigation revealed
      any progression but reduction in size and calcification of osteolytic lesions.
      The local bone density increased and there was no further spread of the disease
      in any of the patients. Inflammatory symptoms resolved in all cases. The only
      side effect was an increase in body temperature up to 38-40 degrees C.
      CONCLUSION: Pamidronate appears to be an effective and well-tolerated therapeutic
      option for patients with fibrous dysplasia. In the future, the combination of the
      metabolic blockage of the dysplasia by pamidronate and limited non-mutilating
      surgical interventions are possible.

PMID- 14729044
TI  - Management of patients with squamous cell carcinoma of the lower lip and N0-neck.
AB  - AIM: For lower lip carcinoma, an incidence of 15% of cervical lymph node
      metastasis at presentation is generally accepted. This is an argument in favour
      of an expectant approach. The purpose of this study was to compare the results of
      the different approaches to the clinically negative neck: prophylactic neck
      dissection, prophylactic neck irradiation and follow-up. MATERIAL AND METHOD: The
      retrospective study included 200 patients with lower lip carcinoma. The following
      data were evaluated: (1) the incidence of cervical lymph node metastasis in
      patients with a clinically negative neck; and (2) pathological confirmation of
      cervical lymph node metastasis. RESULTS: In the group undergoing prophylactic
      neck dissection, lymph node metastasis was found microscopically in 20% of the
      cases. More than half of the patients receiving prophylactic radiotherapy
      developed bulky neck lymph node metastases. Out of the patients attending the 2
      year follow-up 64% developed a clinically positive neck. Cervical lymph node
      metastases in these patients was proven microscopically in 88% of cases.
      CONCLUSION: The high incidence of a clinically positive neck, along with the high
      incidence of neck node metastasis found in neck dissection specimens suggest that
      elective neck dissection is the treatment of choice for the neck in patients with
      lower lip carcinoma.

PMID- 14729045
TI  - Coronoidectomy in maxillary swing for reducing the incidence and severity of
      trismus--a reminder.
AB  - PURPOSE: The maxillary swing approach is a proven method for access to the
      nasopharynx. However, often, trismus is incurred postoperatively, hampering
      adequate oral care and follow-up and affecting patients' quality of life. CASE
      REPORTS: Coronoidectomy was performed in four patients undergoing maxillary
      swing. Minimal trismus was seen in one patient undergoing repeat irradiation and
      chemotherapy. After a 1-month period no trismus was observed in the other three
      patients. CONCLUSION: Coronoidectomy, usually performed in maxillectomy for
      reducing trismus is a useful adjunct in the maxillary swing procedure.

PMID- 14729046
TI  - Repair of large orbito-cutaneous defects by combining two classical flaps.
AB  - INTRODUCTION: Despite the fact that orbital exenteration is one of the most
      socially distressing facial operations, it may be necessary, still. The repair of
      a radically exenterated orbit is a difficult problem for surgeons to resolve.
      MATERIAL AND PATIENTS: In the Department of Oral and Maxillofacial Surgery,
      Madrid, nine patients underwent orbital exenteration including simultaneous
      periorbital tissue resection for invasive orbital and/or periorbital tumours
      between 1990 and 2000. Primary repair was performed by temporalis myofascial plus
      facio-cervico-pectoral flaps. RESULTS: This technique resulted in low morbidity,
      short period of hospitalization and good facial aesthetics.

PMID- 14729047
TI  - Maxillofacial fractures in Hamedan province, Iran: a retrospective study (1987
      2001).
AB  - BACKGROUND: This study presents the various types, causes and incidence, along
      with their clinical management and associated complications of maxillofacial
      fractures at an emergency hospital in Hamedan, Iran. PATIENTS AND METHODS: A
      total of 2268 patients with 3107 facial fractures treated between 1987 and 2001,
      were retrospectively analysed. The average number of fractures for each patient
      was 1.37. Data on the patient's age, gender, cause, site, treatment modalities
      and trauma-associated complications were recorded and assessed. RESULTS: Men 21
      30 years of age sustained the most facial fractures. The ratio of male to female
      was 3.8:1. The age range was 4 months to 90 years (mean 24.6 years). Most
      fractures were caused by motor vehicle accidents (60%, 1360 pts), followed by
      falls (18.9%, 429 pts), and assaults (10%, 227 pts). Isolated mandibular
      fractures (52.6%, 1194 pts) were most common, followed by isolated mid-facial
      fractures (29.5%, 669 pts) and alveolar process fractures (15.1%, 342 pts). 70.8%
      of patients were treated by closed reduction, 17.8% with open procedures and
      11.4% using both. Complications resulting directly from trauma occurred in 5.5%
      of patients. CONCLUSION: The findings support the view that both the causes and
      incidence of maxillofacial fractures vary from one country to another.

PMID- 14729048
TI  - Burn injuries resulting from (accidental) airbag inflation.
AB  - INTRODUCTION: Airbags are intended to minimize facial injuries, alone and when
      used in combination with seatbelts in high-velocity motor-vehicle accidents. They
      may occasionally perforate, resulting in the release of sodium azide or sodium
      hydroxide, which result in chemical burns when in contact with skin. The force of
      deployment may itself result in significant blunt trauma, and there is a
      temperature rise during the inflation causing thermal burns, possibly as a
      separate and unnecessary consequence of a relatively minor accident. METHOD: A
      case report is presented. The literature on such injuries was reviewed and the
      mechanism of airbag deployment commented. CONCLUSION: Alternative designs and
      mechanisms of linking the activation of the device to the velocity of travel or
      to add a switch which is activated when accessing a motorway are recommended.

PMID- 14729049
TI  - The role of simultaneous gap arthroplasty and distraction osteogenesis in the
      management of temporo-mandibular joint ankylosis with mandibular deformity in
      children.
AB  - INTRODUCTION: Temporo-mandibular joint ankylosis is a common cause of acquired
      deformity in children. PURPOSE: Surgical correction of the ankylosis only leaves
      the patient with an uncorrected mandibular deformity. This study was to evaluate
      the use of distraction osteogenesis for simultaneous correction of the mandibular
      deformity. MATERIAL: This study was done on six children with temporo-mandibular
      joint ankylosis and mandibular deformity. Uniaxial double pin distractors with
      Schanz pins were used in this study. METHODS: The patients underwent simultaneous
      gap arthroplasty and mandibular osteotomy (retromolar) with distractor insertion.
      Distraction was started on the fifth post-operative day. The patients were put on
      dynamic temporo-mandibular joint exercises on the first post-operative day.
      RESULTS: All patients had a satisfactory mouth opening on follow-up. Satisfactory
      cosmetic correction of the mandibular deformity was also achieved in all these
      patients. Some degree of malocclusion resulted from treatment due to which the
      patients were placed on orthodontic treatment. CONCLUSIONS: Distraction
      osteogenesis can be used simultaneously with gap arthroplasty in patients with
      temporo-mandibular ankylosis, for the correction of the mandibular deformity.

PMID- 14729050
TI  - Is primary chronic osteomyelitis a uniform disease? Proposal of a classification
      based on a retrospective analysis of patients treated in the past 30 years.
AB  - INTRODUCTION: Primary chronic osteomyelitis of the jaw is a rare, non
      suppurative, chronic inflammatory disease of unknown aetiology. To date,
      classification is confusing due to a non-uniform terminology. The aim of this
      study was to establish a simple (clinical) classification based on patient data
      from our clinic. METHODS: Retrospective analysis revealed 30 cases of which
      clinical course, radiology, pathology, therapy and outcome were analysed.
      RESULTS: Both sexes were equally represented. The mean age at onset of disease
      was 35 years (range 5-76 years). Onset of disease revealed two peaks of
      incidence, one in adolescence and one after age 50 years. While clinical symptoms
      were similar in all cases, an increased intensity of these symptoms was noted in
      younger individuals as well as in the early stages of the disease. Five adults
      and one adolescent presented with additional non facial bone, joint and skin
      manifestations consistent with the diagnosis of SAPHO (synovitis, acne,
      pustulosis, hyperostosis, osteitis) syndrome, or chronic recurrent multifocal
      osteomyelitis. Radiology demonstrated sclerosis, osteolysis and periosteal
      reaction in variable stages in all cases. However, findings were more extensive
      in younger patients. Histology revealed different stages of chronic inflammation
      in all cases. Microabscess formation was noted in 11 cases, six of which were
      children/adolescents. Therapy consisted mainly of surgery, antibiotics and
      hyperbaric oxygen therapy. At the end of the follow up period, 11 patients
      demonstrated complete remission, while in 14 cases amelioration and in 5 no
      significant improvement was noted. CONCLUSION: Based on differences in age at
      presentation, clinical appearance and course, radiology and histology, a
      subclassification into early and adult onset primary chronic osteomyelitis has
      been established. Cases with purely mandibular involvement should further be
      distinguished from cases associated with other syndromes.

PMID- 14729051
TI  - Use of the sandwich osteotomy plus an interpositional allograft for vertical
      augmentation of the alveolar ridge.
AB  - INTRODUCTION: Vertical augmentation of the alveolar ridge is necessary for
      extensive resorption of the alveolar ridge. AIM: To evaluate treatment outcome
      after alveolar ridge augmentation by a sandwich osteotomy combined with an
      interpositional allograft. PATIENTS AND METHODS: The deficient alveolar ridges
      were augmented by a sandwich osteotomy combined with bovine collagen matrix as an
      interpositional allograft placed between the basal bone and the osteotomized
      fragment without fixation. Standardized lateral cephalographs were taken of nine
      patients, before surgery, immediately postoperatively and 3 months after
      augmentation to evaluate the level of augmentation, bone loss and stability of
      the osteotomized fragment. RESULTS: The augmentation ranged between 8.4 and
      11.0mm (mean 9.8mm). Bone resorption in the crestal bone height ranged from 1.5
      to 3.0mm (mean 2.1mm) after 3 months. Bone resorption in thickness of the
      osteotomized fragment ranged from 0.3 to 2.0mm (mean 1.0mm). CONCLUSION: Although
      there was some resorption of the superior and anterior parts of the reconstructed
      alveolar process, it was concluded that this procedure of augmentation is safe.

PMID- 14729052
TI  - Disruption of Ca2+-dependent cell-matrix adhesion enhances c-Src kinase activity,
      but causes dissociation of the c-Src/FAK complex and dephosphorylation of
      tyrosine-577 of FAK in carcinoma cells.
AB  - The nonreceptor tyrosine kinase c-Src is activated in most invasive cancers.
      Activated c-Src binds to FAK in the focal adhesion complex, resulting in the
      activation of the c-Src/FAK signaling cascade, which regulates cytoskeletal
      functions. However, the mechanisms by which c-Src/FAK signaling is regulated
      during conditions of anchorage-independent growth, a hallmark of tumor
      progression, are not clearly known. Here, an in vivo approach to measure c-Src
      activity was studied using phospho-specific antibodies against phosphorylated
      Y418 of c-Src (Src[pY418]), an autophosphorylation site of c-Src, and
      phosphorylated Y577 of FAK (FAK[pY577]), a known substrate of c-Src. Using
      genetic and pharmacological approaches to modulate c-Src activity, we showed that
      the levels of Src[pY418] and FAK[pY577], and the formation of a c-Src/FAK[pY577]
      complex correlated with the activation state of c-Src in adherent cells.
      Interestingly, both the in vivo level of Src[pY418] and in vitro c-Src kinase
      activity were increased in carcinoma cells following disruption of Ca(2+)
      dependent cell-matrix adhesion. In contrast, the level of FAK[pY577] and its
      association with c-Src were reduced in suspended cells. The amount of FAK[pY577]
      in suspended cells was recovered following attachment of rounded cells to
      fibronectin-coated polystyrene beads, indicating that cell spreading was not
      required for phosphorylation of FAK. Moreover, cells expressing activated c-Src
      showed sustained Src[Y418] phosphorylation, but required Ca(2+)-dependent cell
      adhesion for phosphorylation of FAK[Y577] and association of c-Src with
      FAK[pY577]. These findings indicate an important role of integrin-based cell
      matrix adhesion in regulating c-Src/FAK signaling under decreased anchorage
      conditions.

PMID- 14729053
TI  - Cytoplasmic mislocalization of BRCA1 caused by cancer-associated mutations in the
      BRCT domain.
AB  - BRCA1 is inactivated by gene mutations in >50% of familial breast and ovarian
      cancers. BRCA1 is primarily a nuclear protein, although others previously
      reported cytoplasmic staining in breast tumor cells. In this study, we
      demonstrate the cytoplasmic mislocalization of BRCA1 caused by a subgroup of
      clinically relevant cancer mutations. We show that mutations that disrupt or
      delete the C-terminal BRCT domains, but not other regions of BRCA1, caused
      significant relocalization of BRCA1 from nucleus to cytoplasm. Two of the BRCT
      mutations tested (M1775R and Y1853X) are known to adversely affect BRCA1 protein
      folding and nuclear function. The BRCT mutations reduced BRCA1 nuclear import by
      a mechanism consistent with altered protein folding, as indicated by the
      restoration of nuclear staining by more extensive C-terminal deletions.
      Furthermore, we observed increased cytoplasmic staining of both the ectopic and
      endogenous forms of the BRCA1-5382insC mutant (deleted BRCT domain) in HCC1937
      breast cancer cells. Unlike wild-type BRCA1, the BRCA1-5382insC mutant failed to
      form DNA damage-inducible foci when targeted to the nucleus by BARD1. We propose
      that BRCT mutations alter nuclear targeting of BRCA1, and that this may
      contribute to the inhibition of nuclear DNA repair and transcription function.

PMID- 14729054
TI  - Nitric oxide-induced carbonylation of Bcl-2, GAPDH and ANT precedes apoptotic
      events in insulin-secreting RINm5F cells.
AB  - Generation of high levels of nitric oxide (NO) following induction of NOS2 by
      interleukin-1 beta (IL-1beta) triggers beta cell apoptosis in insulin-secreting
      RINm5F cells. Mitochondrial and nuclear events such as downregulation of the
      antiapoptotic protein Bcl-2, activation of the pore responsible for the
      permeability transition (PT) and DNA fragmentation are involved in the process.
      We report in the present paper that exposure of insulin-producing RINm5F cells to
      NO donors and to IL-1beta leads to oxidative carbonylation of both Bcl-2 and the
      adenine nucleotide translocator (ANT) component of the mitochondrial PT pore.
      When the effect of endogenous generation of high concentrations of NO following
      exposure of cells to IL-1beta was studied, carbonylation of Bcl-2 preceded
      downregulation of the protein. Overexpression of Mn-SOD decreases substantially
      the extent of Bcl-2 carbonylation in SIN-1-exposed cells. Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) inhibition, carbonylation and translocation from
      cytoplasm to nucleus and DNA fragmentation were also induced by DETA/NO exposure.
      DETA/NO-induced carbonylation of Bcl-2 and ANT proteins takes place 6 h before
      apoptotic release of histone-associated DNA to cytoplasm. Time course studies
      also reveal a close parallel between GAPDH translocation to nucleus and
      carbonylation. Inhibitors of lipooxidation end products formation such as
      piridoxamine (PM) and aminoguanidine (AG) block NO-triggered carbonylation of Bcl
      2, ANT and GAPDH, prevent NO-induced GAPDH enzyme inhibition and nuclear
      translocation and DNA fragmentation. Our results support the notion that the
      oxidative carbonylation of proteins plays a role in the control of NO-induced
      apoptosis.

PMID- 14729055
TI  - Novel hexad repeats conserved in a putative transporter with restricted
      expression in cell types associated with growth, calcium exchange and
      homeostasis.
AB  - A transport protein is described with 12 transmembrane spans. Within the
      cytoplasmic amino-terminal domain, several novel hexad repeats are conserved in
      human, mouse, rat and pig, four to six of which had the canonical form PS_S_H(+).
      In the carboxyl-terminal domain, a polyglutamate sequence (5-8) is conserved.
      Restricted expression of the transporter was identified in acidophil cells of the
      adult pituitary that secrete growth hormone and prolactin. In the fetus,
      expression was restricted to osteoclasts, chondrocytes, thyroid, pituitary,
      central nervous system, eye, liver and heart. In particular, expression was found
      in structures associated with rapid calcium exchange including the retina,
      cardiomyocytes and in the intraplacental yolk sac that expresses calcitropic
      molecules. Furthermore, expression found in osteoclasts and kidney, within the
      distal portions of nephrons and collecting ducts, was consistent with a role in
      calcium homeostasis. In human pituitary, four mRNA transcripts, and in mouse
      kidney, three mRNA transcripts were expressed. In developing mouse kidney, the
      amount of each transcript varied that suggested the multiple transcripts might be
      differentially expressed in different physiological states. We propose that the
      transporter is specific for a calcium-chelator complex and is important for
      growth and calcium metabolism.

PMID- 14729056
TI  - The human small glutamine-rich TPR-containing protein is required for progress
      through cell division.
AB  - Eukaryotic organisms from yeast to human harbor genes encoding the small
      glutamine-rich tetratricopeptide repeat-containing (SGT) protein. Work presented
      here demonstrated the presence of human SGT (hSGT) protein in a panel of human
      cell lines and throughout the cell cycle. To identify cellular processes in which
      hSGT is involved, knock down populations were analyzed which were generated
      through transfection of hsgt-specific small interfering RNA. Most strikingly,
      depletion of hSGT led to reduced proliferation of the affected cell populations
      while the mitotic index was increased. Time-lapse video microscopy revealed that
      cells from hSGT-depleted populations were unable to complete cell division due to
      mitotic arrest which was frequently followed by cell death. Further evidence for
      a role in cell division was given by the accumulation of hSGT in the midzone and
      the midbody, and by a mitosis-specific migration pattern of hSGT as detected by
      Western blotting after SDS-PAGE or two-dimensional gel electrophoresis. In
      conclusion, results obtained in this study demonstrate that hSGT protein is a
      constitutive component of all human cell lines tested and that this protein is
      essential for successful completion of cell division.

PMID- 14729057
TI  - Variation in cell-substratum adhesion in relation to cell cycle phases.
AB  - The quantification of focal adhesion sites offers an assessable method of
      measuring cell-substrate adhesion. Such measurement can be hindered by intra
      sample variation that may be cell cycle derived. A combination of autoradiography
      and immunolabelling techniques, for scanning electron microscopy (SEM), were
      utilised simultaneously to identify both S-phase cells and their focal adhesion
      sites. Electron-energy 'sectioning' of the sample, by varying the accelerating
      voltage of the electron beam, combined with backscattered electron (BSE) imaging,
      allowed for S-phase cell identification in one energy 'plane' image and
      quantitation of immunogold label in another. As a result, it was possible
      simultaneously to identify S-phase cells and their immunogold-labelled focal
      adhesions sites on the same cell. The focal adhesion densities were calculated
      both for identified S-phase cells and the remaining non-S-phase cells present.
      The results indicated that the cell cycle phase was a significant factor in
      determining the density of focal adhesions, with non-S-phase cells showing a
      larger adhesion density than S-phase cells. Focal adhesion morphology was also
      seen to correspond to cell cycle phase; with 'dot' adhesions being more prevalent
      on smaller non-S-phase and the mature 'dash' type on larger S-phase cells. This
      study demonstrated that when quantitation of focal adhesion sites is required, it
      is necessary to consider the influence of cell cycle phases on any data
      collected.

PMID- 14729058
TI  - Glycogen synthase kinase-3 regulates cytoskeleton and translocation of Rac1 in
      long cellular extensions of human keratinocytes.
AB  - Wound keratinocytes form long cellular extensions that facilitate their migration
      from the wound edge into provisional matrix. We have previously shown that
      similar extensions can be induced by a long-term exposure to EGF or rapidly by
      staurosporine in cultured cells. This morphological change depends on the
      activity of glycogen synthase kinase-3 (GSK-3). Here, we have characterized the
      cytoskeletal changes involved in formation of these extended lamellipodia (E-lam)
      in human HaCaT keratinocytes. E-lams contained actin filaments, stable
      microtubules and keratin intermediate filaments. E-lam formation was prevented by
      cytochalasin D, colchicine and low concentrations of taxol and nocodazole,
      suggesting that actin and microtubule organization and dynamics are essential for
      E-lam formation. Staurosporine induced recruitment of filamentous actin (F
      actin), cortactin, filamin, Arp2/3 complex, Rac1 GTPase and phospholipase C
      gamma1 (PLC-gamma1) to lamellipodia. Treatment of cells with the GSK-3 inhibitors
      SB-415286 and LiCl(2) inhibited E-lam formation and prevented the accumulation of
      Rac1 and Arp2/3 complex at lamellipodia. The formation of E-lams was dependent on
      fibronectin-binding integrins and normally regulated Rac1, and expression of
      either dominant-negative or constitutively active forms of Rac1 prevented E-lam
      formation. Overexpression of either RhoA or Cdc42 GTPases suppressed E-lam
      formation. We conclude that extended lamellipodia formation in keratinocytes
      requires actin and tubulin assembly at the leading edge, and this process is
      regulated by Rac1 downstream of GSK-3.

PMID- 14729059
TI  - Aberrant, persistent inclusion into lipid rafts limits the tumorigenic function
      of membrane type-1 matrix metalloproteinase in malignant cells.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is a key enzyme in cell
      locomotion and tissue remodeling. Trafficking to the plasma membrane and
      internalization into the transient storage compartment both regulate the cell
      surface presentation of MT1-MMP. Our data indicate that mutant MT1-MMP lacking
      the cytoplasmic tail is recruited to the caveolae-enriched lipid raft membrane
      microdomains in breast carcinoma MCF7 cells. In contrast, the wild-type protease
      is not permanently associated with lipid rafts. Trafficking to lipid rafts
      correlated with poor internalization and the persistent presentation of MT1-MMP
      at the cell surface. The tail mutant efficiently functioned in inducing the
      activation of the latent proMMP-2 zymogen, matrix remodeling, and contraction of
      three-dimensional collagen lattices. Recruitment of the tail mutant to lipid raft
      antagonized, however, the cleavage of the plasma membrane-associated E-cadherin.
      These events limited the contribution of the tail mutant to cell locomotion and
      malignant growth. It is conceivable that the tail peptide sequence plays a
      crucial role in the translocations of MT1-MMP across the cell and contributes to
      coordinated cellular functions. It is tempting to hypothesize that the mechanisms
      involved in trafficking of MT1-MMP to caveolin-enriched lipid rafts may be
      targeted in a clinically advantageous manner.

PMID- 14729060
TI  - Protein L-isoaspartyl methyltransferase repairs abnormal aspartyl residues
      accumulated in vivo in type-I collagen and restores cell migration.
AB  - Abnormal aspartyl residue formation such as L-isoaspartates occurs frequently
      during aging in long-lived proteins, resulting in the alteration of their
      structures and biological functions. In this study, we investigated the
      alteration of aspartyl residues in extracellular matrix (ECM) proteins, type-I
      collagen and fibronectin, and in integrin- and ECM-binding motifs during aging,
      as well as the resulting effects on cell biological functions such as migration
      and attachment. Using protein L-isoaspartyl methyltransferase (PIMT) to monitor
      the presence of L-isoaspartyl residues, we showed their accumulation during in
      vivo aging in type-I collagen from rats. In vitro aging of fibronectin as well as
      of peptides containing an integrin- or ECM-binding motif such as RGDSR, KDGEA and
      KDDL also resulted in the formation of L-isoaspartyl residues. While aged
      fibronectin does not alter cell adhesion and migration, type-I collagen aged 20
      months reduced by 65% cell motility, but not adhesion, when compared to 3-month
      aged type-I collagen. Finally, by repairing 20-month-old type-I collagen with
      recombinant PIMT (rPIMT), cell migration was recovered by 72%. These results
      strongly suggest that L-isoaspartyl residue formation in ECM proteins such as
      type-I collagen could play an important role in reducing cell migration and that
      PIMT could be a therapeutic tool to restore normal cell migration in pathological
      conditions where cell motility is crucial.

PMID- 14729061
TI  - uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV.
AB  - Collagen turnover is crucial for tissue homeostasis and remodeling and
      pathological processes such as cancer invasion, but the underlying molecular
      mechanisms are poorly understood. A major pathway appears to be internalization
      and degradation by fibroblasts. We now show that the endocytic transmembrane
      glycoprotein urokinase plasminogen activator receptor-associated protein
      (uPARAP/endo180) directs collagen IV for lysosomal delivery and degradation. In
      wild-type fibroblasts, fluorescently labeled collagen IV was first internalized
      into vesicular structures with diffuse fluorescence eventually appearing
      uniformly within the wild-type cells after longer incubation times. In these
      cells, some collagen-containing vesicles were identified as lysosomes by staining
      for LAMP-1. In contrast, collagen IV remained extracellular and associated with
      fiber-like structures on uPARAP/endo180-deficient fibroblasts. Blocking lysosomal
      cysteine proteases with the inhibitor E64d resulted in strong accumulation of
      collagen IV in lysosomes in wild-type cells, but only very weak intracellular
      fluorescence accumulation in uPARAP/endo180-deficient fibroblasts. We conclude
      that uPARAP/endo180 is critical for targeted delivery of collagen IV to lysosomes
      for degradation implicating the receptor in normal and malignant extracellular
      matrix degradation. A similar localization pattern was observed for collagen V,
      suggesting that uPARAP/endo180 might be generally involved in collagen
      degradation.

PMID- 14729062
TI  - The PDZ-LIM protein RIL modulates actin stress fiber turnover and enhances the
      association of alpha-actinin with F-actin.
AB  - ALP, CLP-36 and RIL form the ALP subfamily of PDZ-LIM proteins. ALP has been
      implicated in sarcomere function in muscle cells in association with alpha
      actinin. The closely related CLP-36 is predominantly expressed in nonmuscle
      cells, where it localizes to actin stress fibers also in association with alpha
      actinin. Here we have studied the expression and functions of RIL originally
      identified as a gene downregulated in H-ras-transformed cells. RIL was mostly
      expressed in nonmuscle epithelial cells with a pattern distinct from that of CLP
      36. RIL protein was found to localize to actin stress fibers in nonmuscle cells
      similarly to CLP-36. However, RIL expression led to partially abnormal actin
      filaments showing thick irregular stress fibers not seen with CLP-36.
      Furthermore, live cell imaging demonstrated altered stress fiber dynamics with
      rapid formation of new fibers and frequent collapse of thick irregular fibers in
      EGFP-RIL-expressing cells. These effects may be mediated through the association
      of RIL with alpha-actinin, as RIL was found to associate with alpha-actinin via
      its PDZ domain, and RIL enhanced the ability of alpha-actinin to cosediment with
      actin filaments. These results implicate the RIL PDZ-LIM protein as a regulator
      of actin stress fiber turnover.

PMID- 14729063
TI  - Low extracellular pH augments TRAIL-induced apoptotic death through the
      mitochondria-mediated caspase signal transduction pathway.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL/APO-2L), a member
      of the tumor necrosis factor (TNF) gene family, is considered as one of the most
      promising cancer therapeutic agents due to its ability to selectively kill tumor
      cells. Although microenvironments of solid tumors (hypoxia, nutrient deprivation,
      and low pH) often affect the effectiveness of chemotherapy, few studies have been
      reported on the relationship between tumor microenvironments and TRAIL. In this
      study, we investigated whether low extracellular pH affects TRAIL-induced
      apoptotic death. When human prostate carcinoma DU145 cells were treated with 200
      ng/ml His-tagged TRAIL for 4 h, the survival was approximately 10% at pH 6.3-6.6
      and 61.3% at pH 7.4. Similar results were observed in human colorectal carcinoma
      CX-1 cell line. The TRAIL-mediated activation of caspase, cytochrome c release,
      and poly (ADP-ribose) polymerase (PARP) cleavage was promoted at low
      extracellular pH. Immunoprecipitation followed by western blot analysis shows
      that low extracellular pH enhances the association of truncated Bid with Bax
      during treatment with TRAIL. Western blot analysis also shows that the low
      extracellular pH-enhanced TRAIL cytotoxicity does not involve modulation of the
      levels of TRAIL receptors (DR4, DR5, and DcR2), FLIP, inhibitor of apoptosis
      (IAP), and Bcl-2. Overexpression of Bcl-2 effectively prevented low extracellular
      pH-augmented TRAIL cytotoxicity. Taken together, we propose that TRAIL-mediated
      cytotoxicity is greatly enhanced in low pH environments by promoting caspase
      activation.

PMID- 14729064
TI  - Expression profiles of 39 HOX genes in normal human adult organs and anaplastic
      thyroid cancer cell lines by quantitative real-time RT-PCR system.
AB  - HOX genes are well known as master control genes in embryonic morphogenesis. We
      hypothesized that HOX genes give cells spatial information to maintain tissue- or
      organ-specificity in adult body and that the deregulated expression of HOX genes
      results in tumor development. We established a comprehensive analysis system to
      quantify expression of 39 human HOX genes based on the real-time reverse
      transcription PCR (RT-PCR) method. Analysis of 39 HOX genes of 20 normal adult
      organs by this system revealed that 5' HOX genes were expressed in organs in the
      caudal parts of the body, and that the more caudal regions the more numbers of
      HOX genes were expressed. It was also found that the expression patterns of HOX
      genes were more similar in the adjacent genes on the same cluster rather than in
      those belonging to the same paralogs. Compared with normal thyroid tissues,
      thyroid cancer cell lines showed the altered expression of some HOX genes,
      especially Abd-B homeobox family genes. Our results showed that HOX genes were
      organ-specifically expressed in adult body and that the deregulated expressions
      of Abd-B family genes were implicated in thyroid tumor development.

PMID- 14729065
TI  - Nuclear localization of the phosphatidylserine receptor protein via multiple
      nuclear localization signals.
AB  - The interaction between phosphatidylserine and its receptor on phagocytic cells
      plays a critical role in the clearance of apoptotic bodies under normal
      physiological condition. A specific receptor for phosphatidylserine (PSR) has
      recently been identified by phage display and shown to mediate phosphatidylserine
      dependent phagocytosis. Here we show that the protein encoded by the PSR cDNA is
      localized in the nuclei through multiple nuclear localization signals. First, a
      fusion between PSR and GFP is localized in the nuclei of transfected cells,
      suggesting that PSR have intrinsic nuclear localization capability. Indeed,
      affinity-purified anti-PSR antibodies identified a 47 kDa protein species in
      cells transfected with untagged PSR and localized this protein in the nuclei by
      immunofluorescent confocal microscopy. In NIH3T3 cells, which express endogenous
      PSR mRNA, a similar 47 kDa species was detected and localized in the nuclei.
      Finally, multiple nuclear localization signals were identified in PSR sequence,
      each capable of targeting GFP to the nuclei. Together, these results suggest that
      PSR may serve a dual role both on the cell surface and in the nuclei.

PMID- 14729066
TI  - TIMP-2 is released as an intact molecule following binding to MT1-MMP on the cell
      surface.
AB  - Binding of tissue inhibitor of metalloproteinase-2 (TIMP-2) to pro-MMP-2 and
      mature membrane type-1 MMP (MT1-MMP) on the cell surface is required for
      activation of MMP-2. It has been reported that following binding to cell surface
      receptors, TIMP-2 undergoes endocytosis and extensive degradation in lysosomes.
      The purpose of this study was to reexamine the fate of TIMP-2 following binding
      to transfected HT1080 cell surface MT1-MMP at 4 degrees C. Following 37 degrees C
      incubation, 125I-TIMP-2 release, endocytosis, and degradation were characterized
      under varying conditions. More than 85% of the total 125I-TIMP-2 bound to cells
      was released as intact functional molecules; <15% was degraded. Transfection of
      HT1080 cells with dominant negative mutant dynamin cDNA resulted in delayed
      endocytosis and release of 125I-TIMP-2 from cells. Pharmacologic agents that
      induce clustering of cell surface receptors (concanavalin A) and interfere with
      endosomal/lysosomal function (bafilomycin A(1)) resulted in enhanced binding of
      125I-TIMP-2 to cell surface receptors. Abrogation of activation of proMT1-MMP
      with a furin inhibitor prevented binding and endocytosis of 125I-TIMP-2.
      Biotinylation of cell surface MT1-MMP followed by Western blotting confirmed the
      presence of mature MT1-MMP on the cell surface and degraded MT1-MMP in the
      intracellular compartment. In conclusion, these studies demonstrate that TIMP-2
      is released from cells primarily as an intact functional molecule following
      binding to MT1-MMP on the cell surface.

PMID- 14729067
TI  - Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta.
AB  - Thymosin beta 4 (Tbeta(4)) stimulates epithelial cell migration and promotes
      laminin-5 (LM-5) expression. Using gene expression analysis with human corneal
      epithelial cells treated with Tbeta(4), we find that both LM-5 gamma2 chain and
      transforming growth factor beta 1 (TGFbeta-1) are increased by more than 2-fold
      over untreated cells. These findings were confirmed by RT-PCR and at the protein
      level. Although TGFbeta-1 increases LM-5 synthesis in a dose-dependent manner, it
      does not appear to be the mechanism by which Tbeta(4) acts on LM-5 gamma2 chain
      synthesis based on three independent experiments. In a time-course analysis,
      Tbeta(4) increases LM-5 gamma2 chain expression at 2 h and peaks at 6 h, while
      TGFbeta-1 increases LM-5 gamma2 chain expression only at 4 h and peaks at 8 h.
      When Tbeta(4)-induced LM-5 gamma2 chain expression is blocked with neutralizing
      antibodies to TGFbeta-1, LM-5 gamma2 chain expression is increased. Finally, in
      TGFbeta-1 knock-out mice, Tbeta(4) increases LM-5 gamma2 chain expression to
      levels higher than that observed in wild-type mice treated with Tbeta(4). These
      findings demonstrate that Tbeta(4) induces both TGFbeta-1 and LM-5 gamma2 chain
      expression in corneal epithelial cells. Tbeta(4) and TGFbeta-1 increase LM-5
      gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further
      increases LM-5 gamma2 chain expression.

PMID- 14729068
TI  - GM3 content modulates the EGF-activated p185c-neu levels, but not those of the
      constitutively activated oncoprotein p185neu.
AB  - The functional relationship between ganglioside GM(3) and two tyrosine-kinase
      receptors, the normal protein p185(c-neu) and the mutant oncogenic protein
      p185(neu), was examined in HC11 cells and in MG1361 cells, respectively. In the
      former, p185(c-neu) expression and activation are controlled by EGF addition to
      the culture medium and by epidermal growth factor receptor (EGFR) activity,
      whereas the latter express unchangingly high levels of constitutively activated
      p185(neu). Studies were carried out using (+/-)-threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol hydrochloride ([D]-PDMP), which inhibits ganglioside
      biosynthesis resulting in ganglioside depletion, and addition of exogenous GM(3)
      to the culture medium. In HC11 cells treated with only [D]-PDMP, p185(c-neu)
      levels remain similar to control cells, whereas levels of tyrosine-phosphorylated
      p185(c-neu) increase after treatment with [D]-PDMP in combination with EGF. When
      exogenous GM(3) is added in combination with [D]-PDMP and EGF, the enhanced
      phosphorylated-p185(c-neu) returns to control levels. Interestingly, EGFR levels
      also vary and, analogously to phosphorylated-p185(c-neu), the increase of EGFR
      content consequent to the [D]-PDMP and EGF addition is reversed by exogenous
      GM(3). In contrast, the addition of neither [D]-PDMP nor exogenous GM(3) modifies
      expression and tyrosine-phosphorylation levels of p185(neu) in MG1361 cells.
      These findings indicate that changes in GM(3) content modulate the tyrosine
      phosphorylated p185(c-neu) levels in a reversible manner, but this is not
      specific for p185(c-neu) because EGFR levels are also modified. Furthermore,
      these data suggest that GM(3) may play a functional role by affecting the
      internalisation pathway of p185(c-neu)/EGFR heterodimers, but not of p185(neu)
      homodimers.

PMID- 14729069
TI  - L-alpha-glycerylphosphorylcholine inhibits the transfer function of
      phosphatidylinositol transfer protein alpha.
AB  - Phosphatidylinositol transfer protein alpha (PITP-alpha) is a bifunctional
      phospholipid transfer protein that is highly selective for phosphatidylinositol
      (PtdIns) and phosphatidylcholine (PtdCho). Polar lipid metabolites, including L
      alpha-glycerylphosphorylcholine (GroPCho), increasingly have been linked to
      changes in cellular function and to disease. In this study, polar lipid
      metabolites of PtdIns and PtdCho were tested for their ability to influence PITP
      alpha activity. GroPCho inhibited the ability of PITP-alpha to transfer PtdIns or
      PtdCho between liposomes. The IC(50) of both processes was dependent on membrane
      composition. D-myo-inositol 1-phosphate and glycerylphosphorylinositol modestly
      enhanced PITP-alpha-mediated phospholipid transfer. Choline, phosphorylcholine
      (PCho), CDP-choline, glyceryl-3-phosphate, myo-inositol and D-myo-inositol 1,4,5
      trisphosphate had little effect. Membrane surface charge was a strong determinant
      of the GroPCho inhibition with the inhibition being greatest for highly anionic
      membranes. GroPCho was shown to enhance the binding of PITP-alpha to anionic
      vesicles. In membranes of low surface charge, phosphatidylethanolamine (PtdEtn)
      was a determinant enabling the GroPCho inhibition. Anionic charge and PtdEtn
      content appeared to increase the strength of PITP-alpha-membrane interactions.
      The GroPCho-enhanced PITP-alpha-membrane binding was sufficient to cause
      inhibition, but not sufficient to account for the extent of inhibition observed.
      Processes associated with strengthened PITP-alpha-membrane binding in the
      presence of GroPCho appeared to impair the phospholipid insertion/extraction
      process.

PMID- 14729070
TI  - Effects of lipid-esterified conjugated linoleic acid isomers on platelet
      function: evidence for stimulation of platelet phospholipase activity.
AB  - The effects of four conjugated linoleic acid (CLA) isomers on in vitro collagen
      induced human platelet aggregation and thromboxane (TXB(2), the inactive
      metabolite of the proaggregatory TXA(2)) production were examined. As the free
      fatty acid (FFA), 9t, 11t-CLA was the most effective inhibitor of these two
      processes (I(50)s of 2.2 and 4 microM, respectively) and the 9c, 11c-CLA was the
      least effective (I(50)s of 8.3 and 37 microM) of the isomers tested. When
      platelets were preesterified with either 25 microM 9t, 11t-CLA or 9c, 11c-CLA,
      CLA incorporation in total platelet lipids increased from 0.24% to 0.31% and
      0.38%, and most of this increase was found to be in the phosphatidyl choline and
      phosphatidyl ethanolamine subclasses. The decrease in arachidonic acid (AA)
      content in total fatty acids or phospholipids was an order of magnitude greater.
      Furthermore, no significant differences between platelets prelabeled with either
      9t, 11t- or 9c, 11c-CLA in the inhibition of collagen-induced aggregation and
      TXB(2) formation were observed. However, platelets prelabeled with 9c, 11c-CLA
      stimulated basal TXB(2) production (4-fold) which was not observed with platelets
      pretreated with either 9t, 11t-CLA, linoleic acid or stearic acid. This
      enhancement was associated with a 2.4-5-fold increase in the release of
      endogenous AA. Our results suggest that the presence of a conjugated cis, cis
      double bond appears to change the lipid environment sufficiently to stimulate the
      basal platelet phospholipase activity, which in turn increases the formation of
      TXB(2).

PMID- 14729071
TI  - Structural analysis of sphingophospholipids derived from Sphingobacterium
      spiritivorum, the type species of genus Sphingobacterium.
AB  - The unique feature of the genus Sphingobacterium is the presence of
      sphingophospholipids and ceramides, besides diacylglycerophospholipids. As major
      cellular lipid components, five kinds of sphingophospholipids were purified from
      Sphingobacterium spiritivorum ATCC 33861(T), the type species of genus
      Sphingobacterium. They were identified as ceramide phosphorylethanolamines (CerPE
      1 and CerPE-2), ceramide phosphoryl-myo-inositols (CerPI-1 and CerPI-2), and
      ceramide phosphorylmannose (CerPM-1). The ceramide of CerPE-1, CerPI-1, and CerPM
      1 was composed of 15-methylhexadecasphinganine (isoheptadeca sphinganine, iso
      C17:0) and 13-methyltetradecanoic acid (isopentadecanoic acid, iso-C15:0),
      whereas that of CerPE-2 and CerPI-2 was composed of isoheptadeca sphinganine and
      2-hydroxy-13-methyltetradecanoic acid (2-hydroxy isopentadecanoic acid, 2-OH iso
      C15:0). These sphingophospholipids were also found in cellular lipids of
      Sphingobacterium multivorum ATCC 33613(T), Sphingobacterium mizutaii ATCC
      33299(T), Sphingobacterium faecium IFO 15299(T), Sphingobacterium thalpophilum
      ATCC 43320(T), and Sphingobacterium antarcticum ATCC 51969(T). To our knowledge,
      the existence of CerPM-1 is a novel sphingophospholipid through eukaryotic and
      prokaryotic cells.

PMID- 14729072
TI  - Inhibition of apolipoprotein B secretion by taurocholate is controlled by the N
      terminal end of the protein in rat hepatoma McArdle-RH7777 cells.
AB  - Bile salts (BS) inhibit the secretion of apolipoprotein B (apoB) and
      triacylglycerol (TG) in primary rat, mouse and human hepatocytes and in mice in
      vivo. We investigated whether lipidation of apoB into a lipoprotein particle is
      required for this inhibitory action of BS. The sodium/taurocholate co
      transporting polypeptide (Ntcp) was co-expressed in McArdle-RH7777 (McA-RH7777)
      cells stably expressing the full-length human apoB100 (h-apoB100, secreted as TG
      rich lipoprotein particles) or carboxyl-truncated human apoB18 (h-apoB18,
      secreted in lipid-free form). The doubly transfected cell lines (h-apoB/r-Ntcp)
      effectively accumulated taurocholic acid (TC). TC incubation decreased the
      secretion of endogenous rat apoB100 (-50%) and h-apoB18 (-35%), but did not
      affect secretion of rat apoA-I. Pulse-chase experiments (35S-methionine)
      indicated that the impaired secretion of radiolabeled h-apoB18 and h-apoB100 was
      associated with accelerated intracellular degradation. The calpain protease
      inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) partially inhibited
      intracellular apoB degradation but did not affect the amount of either h-apoB18
      or h-apoB100 secreted into the medium, indicating that inhibition of apoB
      secretion by TC is not due to calpain-dependent proteasomal degradation. We
      conclude that TC does not inhibit apoB secretion by interference with its
      lipidation, but rather involves a mechanism dependent on the N-terminal end of
      apoB.

PMID- 14729073
TI  - Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human
      leukemia cell line, MEG-O1.
AB  - The prolonged treatment with phorbol 12-myristate 13-acetate (PMA) of a human
      megakaryoblastic leukemia cell line, MEG-O1, induced increase of sphingosine
      kinase (SPHK) enzyme activity and SPHK1 protein expression as well as SPHK1
      message. Protein kinase C (PKC) inhibitor prevented the PMA-induced SPHK1 gene
      expression. To elucidate the regulatory mechanism of this gene expression, we
      examined the promoter area (distal to the first exon) and its binding proteins.
      Luciferase analyses showed that the area of 300 bp from the first exon was
      sufficient for PMA-responsiveness, and that specificity protein 1 (Sp1)- and two
      activator protein 2 (AP-2)-binding motifs within this area were necessary for
      responsiveness. Inhibitors for PKC and MEK1 decreased this PMA-induced promoter
      activity. Electrophoresis mobility shift assay (EMSA) showed that Sp1 protein was
      originally bound to the Sp1 site and that two additional bands bound to the two
      AP-2 motifs were observed only when stimulated with PMA in MEG-O1 cells. The
      appearance of these bands resulted from binding to an unknown protein rather than
      AP-2. These results indicated that PMA up-regulates SPHK1 gene expression through
      PMA-responsive elements of the 5' promoter area of the gene, and suggested that
      PMA-mediated SPHK1 gene expression would be mediated via PKC- and ERK-dependent
      signal transduction pathway by binding the transcription factor to AP-2 motifs.

PMID- 14729074
TI  - Low density lipoprotein induces eNOS translocation to membrane caveolae: the role
      of RhoA activation and stress fiber formation.
AB  - A decrease in the bioavailability of endothelium-derived nitric oxide (NO) is
      linked to hypercholesterolemia. However, the mechanism by which low density
      lipoprotein (LDL) mediates endothelial NO synthase (eNOS) dysfunction remains
      controversial. We investigate the effect of LDL on eNOS regulation in human
      endothelial cells (ECs). In cultured ECs, a high level of LDL increased the
      abundance of eNOS and caveolin-1 (Cav-1) in the membrane caveolae and the
      association of eNOS with Cav-1. Furthermore, it decreased the basal level of NO
      and blocked NO production stimulated by the calcium ionophore A23187. LDL
      exposure also increased the formation of stress fibers and the membrane
      translocation of eNOS. These effects can be blocked by cytochalasin D, an actin
      cytoskeleton disruptor. In revealing the mechanism underlying the translocation
      of eNOS, we found that a high level of LDL increased the level of membrane
      associated and GTP-formed RhoA and activated the RhoA downstream kinase ROCK-1
      activity. Y-27632, a specific inhibitor of ROCK-1, blocked LDL-induced stress
      fiber formation, eNOS translocation and NO production. In conclusion, a high
      level of LDL increases the movement of eNOS to membrane caveolae via the
      increased stress fibers. The RhoA-mediated pathway may play a crucial role in
      this process in vascular ECs.

PMID- 14729075
TI  - Interaction of apolipoprotein A-I with lecithin-cholesterol vesicles in the
      presence of phospholipase C.
AB  - Here we study the anti-nucleating mechanism of apolipoprotein A-I (apo A-I) on
      model biliary vesicles in the presence of phospholipase C (PLC) utilizing dynamic
      light scattering (DLS), steady-state fluorescence spectroscopy, cryogenic
      transmission electron microscopy (cryo-TEM), and UV/Vis spectroscopy. PLC induces
      aggregation of cholesterol-free lecithin vesicles from an initial, average size
      of 100 nm to a maximal size of 600 nm. The presence of apo A-I likely inhibits
      vesicle aggregation by shielding the PLC-generated hydrophobic moieties, which
      results in vesicles of an average size of 200 nm. A similar phenomenon is
      observed in cholesterol-enriched lecithin vesicles. Whereas PLC alone produces
      aggregates of 300 nm, no aggregation is observed when apo A-I is present along
      with PLC. However, the ability of apo A-I to inhibit aggregation is temporary,
      and after 8 h, a broad particle size distribution with sizes as high as 800 nm is
      observed. Apo A-I possibly induces the formation of small apo A
      I/lecithin/cholesterol complexes of about 5-20 nm similar to the discoidal pre
      HDL complexes found in blood when it can no longer effectively shield all the DAG
      molecules. Concomitant with formation of complexes, DAG molecules coalesce into
      large oil droplets, which account for the large particles observed by light
      scattering. Thus, apo A-I acts as an anti-nucleating agent by two mechanisms,
      anti-aggregation and microstructural transition. The mode of protection is
      dependent on the cholesterol content and the relative amounts of DAG and apo A-I
      present. This study supports the possibility of apo A-I solubilizing lipids in
      bile in a similar fashion as it does in blood and also delineates the mechanism
      of formation of the complexes.

PMID- 14729076
TI  - Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to
      improve transfection efficacy.
AB  - Currently, the major drawback of gene therapy is the gene transfection rate. The
      two main types of vectors that are used in gene therapy are based on viral or non
      viral gene delivery systems. The viral gene delivery system shows a high
      transfection yield but it has many disadvantages, such as oncogenic effects and
      immunogenicity. However, cationic polymers, like chitosan, have potential for DNA
      complexation and may be useful as non-viral vectors for gene therapy
      applications. Chitosan is a natural non-toxic polysaccharide, it is biodegradable
      and biocompatible, and protects DNA against DNase degradation and leads to its
      condensation. The objective of this paper was to summarize the state of the art
      in gene therapy and particularly the use of chitosan to improve the transfection
      efficiency in vivo and in vitro.

PMID- 14729077
TI  - Thiolated chitosans.
AB  - The derivatization of the primary amino groups of chitosan with coupling reagents
      bearing thiol functions leads to the formation of thiolated chitosans. So far,
      three types of thiolated chitosans have been generated: chitosan-cysteine
      conjugates, chitosan-thioglycolic acid conjugates and chitosan-4-thio-butyl
      amidine conjugates. Various properties of chitosan are improved by this
      immobilization of thiol groups. Due to the formation of disulfide bonds with
      mucus glycoproteins, the mucoadhesiveness is 6--100-fold augmented (I). The
      permeation of paracellular markers through intestinal mucosa can be enhanced 1.6-
      3-fold utilizing thiolated instead of unmodified chitosan (II). Moreover,
      thiolated chitosans display in situ-gelling features, due to the pH-dependent
      formation of inter- as well as intra-molecular disulfide bonds (III). This latter
      process provides a strong cohesion and stability of carrier matrices being based
      on thiolated chitosans (IV). Consequently, thiolated chitosans can guarantee a
      prolonged controlled release of embedded therapeutic ingredients (V). The
      potential of thiolated chitosans has meanwhile also been demonstrated in vivo. A
      significant pharmacological efficacy of 1.3% of orally given salmon calcitonin,
      for instance, could be achieved utilizing thiolated chitosan as polymeric drug
      carrier matrix, while no effect was reached using unmodified chitosan. According
      to these results thiolated chitosans represent a promising new category of
      polymeric excipients in particular for the non-invasive administration of
      hydrophilic macromolecules. Further applications such as their use as scaffold
      materials in tissue engineering or as coating material for stents seem feasible.

PMID- 14729078
TI  - Structure and interactions in covalently and ionically crosslinked chitosan
      hydrogels for biomedical applications.
AB  - This review presents a critical analysis of covalently and ionically crosslinked
      chitosan hydrogels and related networks for medical or pharmaceutical
      applications. The structural basis of these hydrogels is discussed with reference
      to the specific chemical interactions, which dictate gel formation. The synthesis
      and chemistry of these hydrogels is discussed using specific pharmaceutical
      examples. Covalent crosslinking leads to formation of hydrogels with a permanent
      network structure, since irreversible chemical links are formed. This type of
      linkage allows absorption of water and/or bioactive compounds without dissolution
      and permits drug release by diffusion. pH-controlled drug delivery is made
      possible by the addition of another polymer. Ionically crosslinked hydrogels are
      generally considered as biocompatible and well-tolerated. Their non-permanent
      network is formed by reversible links. Ionically crosslinked chitosan hydrogels
      exhibit a higher swelling sensitivity to pH changes compared to covalently
      crosslinked chitosan hydrogels. This extends their potential application, since
      dissolution can occur in extreme acidic or basic pH conditions.

PMID- 14729079
TI  - Structure and interactions in chitosan hydrogels formed by complexation or
      aggregation for biomedical applications.
AB  - The aim of this review was to provide a detailed overview of physical chitosan
      hydrogels and related networks formed by aggregation or complexation, which are
      intended for biomedical applications. The structural basis of these systems is
      discussed with particular emphasis on the network-forming interactions, the
      principles governing their formation and their physicochemical properties. An
      earlier review discussing crosslinked chitosan hydrogels highlighted the
      potential negative influence on biocompatibility of covalent crosslinkers and
      emphasised the need for alternative hydrogel systems. A possible means to avoid
      the use of covalent crosslinkers is to prepare physical chitosan hydrogels by
      direct interactions between polymeric chains, i.e. by complexation, e.g.
      polyelectrolyte complexes (PEC) and chitosan/poly (vinyl alcohol) (PVA)
      complexes, or by aggregation, e.g. grafted chitosan hydrogels. PEC exhibit a
      higher swelling sensitivity towards pH changes compared to covalently crosslinked
      chitosan hydrogels, which extends their potential application. Certain complexed
      polymers, such as glycosaminoglycans, can exhibit interesting intrinsic
      properties. Since PEC are formed by non-permanent networks, dissolution can
      occur. Chitosan/PVA complexes represent an interesting alternative for preparing
      biocompatible drug delivery systems if pH-controlled release is n/ot required.
      Grafted chitosan hydrogels are more complex to prepare and do not always improve
      biocompatibility compared to covalently crosslinked hydrogels, but can enhance
      certain intrinsic properties of chitosan such as bacteriostatic and wound-healing
      activity.

PMID- 14729080
TI  - A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel.
AB  - A novel injectable thermosensitive in situ gelling hydrogel has been developed.
      The system, which falls under the BST-Gel platform technology developed at
      Biosyntech Inc. (Laval, QC, Canada), consists of a chitosan solution (C)
      neutralized with beta-glycerophosphate (GP) that is liquid at room temperature
      but gels when heated to body temperature. We propose to use this thermosensitive
      hydrogel for the sustained release of paclitaxel at tumor resection sites in
      order to prevent local tumor recurrence. The in vitro release profiles
      demonstrated controlled delivery over 1 month. The initial drug loading
      substantially affected the release. Local delivery of paclitaxel from the
      formulation injected intratumorally was investigated using EMT-6 tumors implanted
      subcutaneously on Balb/c mice. These experiments showed that one intratumoral
      injection of the thermosensitive hydrogel containing paclitaxel was as
      efficacious as four intravenous injections of Taxol in inhibiting the growth of
      EMT-6 cancer cells in mice, but in a less toxic manner. Further histological
      analysis revealed that while the proportion of necrotic areas was similar for the
      C/GP/paclitaxel and the Taxol-treated tumors, a disparity between tumor
      associated inflammatory cell populations may suggest differing anti-tumor
      mechanisms.

PMID- 14729081
TI  - Comparative studies on polyelectrolyte complexes and mixtures of chitosan
      alginate and chitosan-carrageenan as prolonged diltiazem clorhydrate release
      systems.
AB  - The aim of this work was to evaluate the possibility of using mixtures and/or
      polyelectrolyte complexes from both chitosan-alginate and chitosan-carrageenan as
      prolonged drug release systems. Different dissolution profiles were obtained by
      changing the polymer matrix system (chitosan-alginate or chitosan-carrageenan)
      and the method used to include these polymers into the formulation (physical
      mixture or polyelectrolyte complex). Drug dissolution profiles from the matrices
      have been discussed by considering the swelling behavior of the polymers used.
      The swelling behavior of the chitosan-carrageenan and chitosan-alginate systems
      was analyzed by using the Hopfenberg model which permits to separate the
      diffusional contribution, kf, from the relaxational contribution, kr, involved in
      solvent penetration/sorption in glassy polymers. The chitosan-alginate system is
      better than the chitosan-carrageenan system as prolonged drug release matrix
      because the drug release is controlled at low percentage of the polymers in the
      formulation, the mean dissolution time is high, and different dissolution
      profiles could be obtained by changing the mode of inclusion of the polymers.
      Good agreement between td and kf/kr values for the system chitosan-alginate was
      found, which means that the swelling behavior of the polymers controlled the drug
      release from the matrix. In the case of the system chitosan-carrageenan, the high
      capacity of carrageenan promotes the entry of water into the tablet and therefore
      the main mechanism of drug release would be the disintegration instead of the
      swelling of the matrix.

PMID- 14729082
TI  - Influence of methylation process on the degree of quaternization of N-trimethyl
      chitosan chloride.
AB  - N-Trimethyl chitosan chloride (TMC) is a soluble chitosan derivative that shows
      effective enhancing properties for peptide and protein drug transport across
      mucosal membranes. TMC was synthesized by reductive methylation of chitosan in an
      alkaline environment at elevated temperature. The number of methylation process
      steps and the base used in the process was demonstrated to affect the degree of
      quaternization of the primary amino group and methylation of 3- and 6-hydroxyl
      groups. 1H-Nuclear magnetic resonance spectra showed that the degree of
      quaternization of TMC was higher when using sodium hydroxide as the base compared
      to using dimethyl amino pyridine. The degrees of quaternization as well as O
      methylation of TMC increased with the number of reaction steps. O-Methylation
      resulted in decreased solubility of TMC. The high degree of quaternization of TMC
      with a low degree of O-methylation was prepared by employing one reaction step
      with two subsequent addition steps and a controlled alkaline environment of the
      mixture reaction.

PMID- 14729083
TI  - N-trimethyl chitosan chloride as absorption enhancer in oral peptide drug
      delivery. Development and characterization of minitablet and granule
      formulations.
AB  - In this study, minitablet and granule formulations were developed as solid oral
      dosage forms for the delivery of peptide drugs with the absorption enhancer N
      trimethyl chitosan chloride (TMC). Minitablets were deemed suitable as a dosage
      form due to their ability, as components of multiple unit dosage forms (MUDFs),
      to disperse from each other, before disintegration, effectively increasing the
      area in which the polymer can assert its absorption-enhancing effect. The polymer
      should be released from the dosage forms prior to the release of the peptide,
      which was, together with achieving maximum release of both ingredients, the main
      focus of this study. Desmopressin (1-(3-mercaptopropionic acid)-8-D-arginine
      vasopressin monoacetate (DDAVP) was used as model peptide drug. The optimized
      minitablet formulation consisted of two types of granules, namely DDAVP and TMC
      granules. DDAVP granules, containing tetraglycerol pentastearate (TGPS), were
      specifically aimed at delaying the release of the peptide from the dosage form.
      Burst release of TMC was attempted with TMC granules. Both these granule types
      were included in the granule formulation. Release profiles for both the optimized
      minitablet formulation as well as the granule formulation showed that the release
      of DDAVP was effectively delayed from the formulation compared to the formulation
      where no attempt at delaying the release was made. In comparison, more TMC was
      released, and at a faster rate, from the granule formulation than the optimized
      minitablet formulations. Both the optimized minitablet formulation and the
      granule formulation show suitable release profiles for the delivery of peptide
      drugs with TMC as absorption enhancer in solid oral dosage forms.

PMID- 14729084
TI  - Comparison of the effect of chitosan and polyvinylpyrrolidone on dissolution
      properties and analgesic effect of naproxen.
AB  - The solubilizing and absorption enhancer properties towards naproxen of chitosan
      and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems
      prepared at various drug-polymer ratios by mixing, cogrinding or kneading, were
      characterized by differential scanning calorimetry, X-ray diffractometry, Fourier
      transform infrared spectroscopy, and scanning electron microscopy, and tested for
      dissolution behavior. Both carriers improved drug dissolution and their
      performance depended on the drug-polymer ratio and the system preparation method.
      Chitosan was more effective than PVP, despite the greater amorphizing power of
      PVP as revealed by solid state analyses. The 3/7 (w/w) drug-carrier coground
      systems with chitosan and PVP were the best products enabling, respectively, an
      improvement of 4.8 and 3.6 times of drug dissolution efficiency. In vivo
      experiments in mice demonstrated that administration of 45 mg/kg of drug coground
      with PVP or chitosan resulted, respectively, in a 25 and 60% reduction of acetic
      acid-induced writhings in comparison to pure drug, which, instead, was
      statistically ineffective as compared to the control group. Moreover, the 3/7
      (w/w) drug-chitosan coground product demonstrated an antiwrithing potency 2.4
      times higher than the coground with PVP. Thus, the direct-compression properties
      and antiulcerogenic activity, combined with the demonstrated solubilizing power
      and analgesic effect enhancer ability towards the drug, make chitosan
      particularly suitable for developing a reduced-dose fast-release solid oral
      dosage form of naproxen.

PMID- 14729085
TI  - A method for direct preparation of chitosan with low molecular weight from fungi.
AB  - By modifying the common method for the preparation of chitosan from fungi, low
      molecular weight chitosan with an average MW of 4.5 x 10(4) g/mol and a numerical
      MW of 1.7 x 10(4) g/mol can be directly extracted from the raw material without
      the need of thermal or chemical depolymerization. Based on the solubility of low
      molecular chitosan up to alkaline pH ranges, reprecipitation and washing with
      ethanol is required to keep the low molecular fraction within the preparation.
      The use of water for washing between the preparation steps would cause solving
      and discarding of the low molecular chitosan. The chitosan was analyzed by laser
      light scattering and 1H-NMR spectroscopy.

PMID- 14729086
TI  - Production of chitosan pellets by extrusion/spheronization.
AB  - Chitosan pellets were successfully prepared using the extrusion/spheronization
      technology. Microcrystalline cellulose was used as additive in concentrations
      from 70 to 0%. The powder mixtures were extruded using water and diluted acetic
      acid solution in different powder to liquid ratios. The effects on bead formation
      using water and different acetic acid concentrations and solution quantities were
      analysed. Also, the morphological and mechanical characteristics of the obtained
      beads were investigated. With demineralized water as granulation fluid, pellets
      with a maximum of 50% (m/m) of chitosan could be produced. The mass fraction of
      chitosan within the pellets could be increased to 100% by using diluted acetic
      acid for the granulation step.

PMID- 14729087
TI  - Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery:
      synthesis and in vitro evaluation.
AB  - The aim of the present study was to evaluate the influence of the degree of
      modification and the polymer chain length on the mucoadhesive properties and the
      swelling behavior of thiolated chitosan derivatives obtained via a simple one
      step reaction between the polymer and 2-iminothiolane. The conjugates differing
      in molecular mass of the polymer backbone and in the amount of immobilized thiol
      groups were compressed into tablets. They were investigated for their
      mucoadhesive properties on freshly excised porcine mucosa via tensile studies and
      the rotating cylinder method. Moreover, the swelling behavior of these tablets in
      aqueous solutions was studied by a simple gravimetric method. The obtained
      results demonstrated that the total work of adhesion of chitosan-TBA (=4-thio
      butyl-amidine) conjugates can be improved by an increasing number of covalently
      attached thiol groups; a 100-fold increase compared to unmodified chitosan was
      observed for a medium molecular mass chitosan-TBA conjugate exhibiting 264 microM
      thiol groups per gram polymer. Also, the polymer chain length had an influence on
      the mucoadhesive properties of the polymer. The medium molecular mass polymer
      displayed a fourfold improved adhesion on the rotating cylinder compared to the
      derivative of low molecular mass. These results contribute to the development of
      new delivery systems exhibiting improved mucoadhesive properties.

PMID- 14729088
TI  - Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine
      delivery in mice.
AB  - High molecular weight (Mw) chitosan (CS) solutions have already been proposed as
      vehicles for nasal immunization. The aim of the present work was to investigate
      the potential utility of low Mw CS in the form of nanoparticles as new long-term
      nasal vaccine delivery vehicles. For this purpose, CS of low Mws (23 and 38 kDa)
      was obtained previously by a depolymerization process of the commercially
      available CS (70 kDa). Tetanus toxoid (TT), used as a model antigen, was
      entrapped within CS nanoparticles by an ionic cross-linking technique. TT-loaded
      nanoparticles were first characterized for their size, electrical charge, loading
      efficiency and in vitro release of antigenically active toxoid. The nanoparticles
      were then administered intranasally to conscious mice in order to study their
      feasibility as vaccine carriers. CS nanoparticles were also labeled with FITC-BSA
      and their interaction with the rat nasal mucosa examined by confocal laser
      scanning microcopy (CLSM). Irrespective of the CS Mw, the nanoparticles were in
      the 350 nm size range, and exhibited a positive electrical charge (+40 mV) and
      associated TT quite efficiently (loading efficiency: 50-60%). In vitro release
      studies showed an initial burst followed by an extended release of antigenically
      active toxoid. Following intranasal administration, TT-loaded nanoparticles
      elicited an increasing and long-lasting humoral immune response (IgG
      concentrations) as compared to the fluid vaccine. Similarly, the mucosal response
      (IgA levels) at 6 months post-administration of TT-loaded CS nanoparticles was
      significantly higher than that obtained for the fluid vaccine. The CLSM images
      indicated that CS nanoparticles can cross the nasal epithelia and, hence,
      transport the associated antigen. Interestingly, the ability of these
      nanoparticles to provide improved access to the associated antigen to the immune
      system was not significantly affected by the CS Mw. Indeed, high and long-lasting
      responses could be obtained using low Mw CS molecules. Furthermore, the response
      was not influenced by the CS dose (70-200 microg), achieving a significant
      response for a very low CS dose. In conclusion, nanoparticles made of low Mw CS
      are promising carriers for nasal vaccine delivery.

PMID- 14729089
TI  - Gamma scintigraphic evaluation of the fate of microcrystalline chitosan granules
      in human stomach.
AB  - In several reports of in vitro studies it has been suggested that the
      mucoadhesive chitosans could be of value in preparing gastro-retentive
      formulations. The aim of this study was to obtain direct in vivo evidence of
      whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive
      systems in humans. Neutron-activation-based gamma scintigraphy was used to study
      gastric residence times of MCCh granules in healthy male volunteers. Possible
      effects of neutron irradiation on the properties of the MCCh granules were
      studied in advance, in vitro. In vivo gamma scintigraphic evaluations were
      carried out with the subjects in a fasted state, using granules containing 95%
      (F1) or 40% (F2) of MCCh of molecular weight 150 kDa. Reference formulation (F3)
      was lactose granules. The reference granules passed rapidly from the stomach
      (mean t50% 0.5+/-0.3 h (n=5)). MCCh in granules prolonged gastric residence times
      of the formulations in only a few cases (in one volunteer in the F1 group (n=4)
      and in two volunteers in the F2 group (n=5)). Maximum individual t50% values were
      2.1 h (F1) and 2.3 h (F2). It was concluded that the in vivo mucoadhesion of MCCh
      formulations is erratic, and that the formulations studied are not reliable
      gastro-retentive drug delivery systems.

PMID- 14729096
TI  - Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin
      and cetiedil.
AB  - Quinidine and Ba(2+), non-selective K(+)-channel blockers, have previously been
      shown to inhibit antigen-induced mediator (beta-hexosaminidase) release from RBL
      2H3 cells, a mucosal-type mast cell line. We therefore used selective blockers of
      Ca(2+)-activated and other K(+) channels to determine if there was a role for
      these channels in antigen-induced mediator release. Charybdotoxin and cetiedil
      dose-dependently inhibited beta-hexosaminidase release with IC(50) values of 133
      nM and 84 microM, respectively. Charybdotoxin also inhibited the repolarization
      phase of the antigen-induced biphasic change in the membrane potential (IC(50) 84
      nM), antigen-stimulated 86Rb(+)-efflux and increase in free intracellular
      calcium, [Ca(2+)](i). Iberiotoxin, margatoxin, apamin and tetraethylammonium had
      no effect on beta-hexosaminidase release. These results suggest that K(+)
      conductances play a significant role in mediator release from RBL-2H3, that these
      conductances are of the intermediate conductance Ca(2+)-activated K(+) channel
      (IK(Ca)) type, and that they are somewhat similar to those which have been
      described in red blood cells, though they are much less sensitive to
      clotrimazole.

PMID- 14729090
TI  - Scintigraphic verification of adherence of a chitosan formulation to the human
      oesophagus.
AB  - It is well known that adherence of a drug product, e.g. a gelatine capsule, to
      the oesophagus can cause oesophageal injury, which can be severe if the medicinal
      agent has corrosive properties. In a recent study we investigated by means of
      gamma scintigraphy whether chitosan granules dispensed in gelatine capsules had
      gastro-retentive properties. In one of ten volunteers the formulation lodged in
      the oesophagus. This case is reported here. The capsule adhered initially to the
      distal oesophagus. The capsule shell had started to disintegrate within 5 min,
      with some radioactivity detectable in the stomach. However, about two thirds of
      the radioactivity remained detectable in the oesophageal region for 1.75 h. This
      could be explained on the basis that there had been adherence not only of the
      gelatine shell but also of chitosan granules to the oesophageal mucosa. In
      evaluating potential for causing oesophageal injury it is not enough to consider
      only the mucoadhesive properties of the outermost layer of a drug product,
      because the filler may also have such properties. When new excipient materials
      are introduced, evaluation of their mucoadhesive tendencies is important.

PMID- 14729097
TI  - Inhibition of the antigen-induced activation of RBL-2H3 cells by cetiedil and
      some of its analogues.
AB  - Our previous studies on rat basophilic leukaemia (RBL-2H3) cells suggested that
      IK(Ca) channels similar to those in red blood cells (RBC) may be involved in the
      antigen-induced beta-hexosaminidase release. Since cetiedil blocks these channels
      in both cell types, we studied the inhibition by a selection of the synthetic
      analogues of cetiedil (UCL compounds) of antigen-induced beta-hexosaminidase
      release and 86Rb(+)-efflux from RBL-2H3 cells. We tested the (+)- and (-)
      enantiomers of cetiedil (UCL 1348 and UCL 1349), the more lipophilic
      triphenylacetic acid derivatives (UCL 1495 and UCL 1617) and (9-benzyl-fluoren)-9
      yl derivatives (UCL 1608 and UCL 1710). They all inhibited antigen-induced beta
      hexosaminidase release and 86Rb(+)-efflux. Their relative potency in inhibiting
      antigen-induced beta-hexosaminidase release was UCL
      1608>1710>1617>1348>1349>1495, with IC(50) values of 9.6+/-0.6, 14.4+/-2.2,
      23.4+/-1.4, 29.8+/-1.1, 77.5+/-11.8 and 104.6+/-14.7 (microM), respectively.
      These IC(50)s suggest some dissimilarity between IK(Ca) in RBL-2H3 cells and RBC.
      Lipophilicity and potency were well correlated in RBC, but not in RBL-2H3 cells.

PMID- 14729098
TI  - Direct block by bisindolylmaleimide of the voltage-dependent K+ currents of rat
      mesenteric arterial smooth muscle.
AB  - We investigated the effect of bisindolylmaleimide (I), a widely used protein
      kinase C (PKC) inhibitor, on the voltage-dependent K(+) (Kv) currents of rat
      mesenteric arterial smooth muscle cells using the whole-cell patch-clamp
      technique. Bisindolylmaleimide (I) reversibly and dose-dependently inhibited the
      Kv currents with an apparent K(d) value of 0.23+/-0.001 microM. The blockade was
      apparently through the acceleration of the decay rate of the Kv currents. The
      apparent rate constants of association and dissociation for bisindolylmaleimide
      (I) were 17.9+/-1.6 microM(-1) s(-1) and 4.1+/-1.5 s(-1), respectively. The
      inhibition of Kv current by bisindolylmaleimide (I) was steeply voltage-dependent
      between -30 and 0 mV (voltage range of channel activation). Bisindolylmaleimide
      (I) had no effect on the steady-state activation and inactivation of the Kv
      currents. Applications of trains of pulses at 1 or 2 Hz lead to a progressive
      increase in the bisindolylmaleimide (I)-blockade, and the recovery from
      bisindolylmaleimide (I)-block at -80 mV exhibited a time constant of 577.2+/-52.7
      ms. Bisindolylmaleimide (V), an inactive analogue of bisindolylmaleimide (I),
      similarly inhibited the Kv currents with an apparent K(d) value of 1.48+/-0.004
      microM, but other PKC inhibitor chelerythrine little affected the Kv currents.
      These results suggest that bisindolylmaleimide (I) directly inhibits the Kv
      currents of rat mesenteric arterial smooth muscle cells independently of PKC
      inhibition, in a state-, voltage-, time- and use-dependent manner.

PMID- 14729099
TI  - Antitumor antibiotic streptonigrin and its derivatives as inhibitors of nitric
      oxide-dependent activation of soluble guanylyl cyclase.
AB  - The influence of streptonigrin on the activity of human platelet guanylyl cyclase
      was investigated. Streptonigrin (0.1-5 microM) had no effect on the basal
      activity of the enzyme, but inhibited in a concentration-dependent manner the
      sodium nitroprusside-induced activation of human platelet soluble guanylyl
      cyclase with an IC(50) value of 4.16 microM. Streptonigrin (10 microM) also
      inhibited (by 28%) the activation of the enzyme by the direct nitric oxide (NO)
      donor-spermine-NONO (100 microM), but had no influence on the stimulation of
      soluble guanylyl cyclase by protoporphyrin IX. The absence of a correlation
      between the inhibition of NO-stimulated guanylyl cyclase activity by
      streptonigrin (I) and its derivatives (streptonigrone (IV), streptonigrone-2'
      imine (V), amide of 1 and 2'-deoxy-2'-amino-D-glucose (VI), amide of 1 and 2'
      deoxy-2'-amino-2'-D-galactose (VII), amide of 1 and 1-O-methyl-6-deoxy-6-amino-D
      glucose (VIII), diphenylmethyl ester of I (IX), conjugate of I and daunorubicin
      (X)), and the level of cytotoxic effects of these compounds excludes the
      involvement of guanylyl cyclase in the mechanism of antitumor action of
      streptonigrin. Inhibition of guanylyl cyclase activation by NO donors but not by
      protoporphyrin IX represents a new biochemical effect of streptonigrin, which
      should be taken into account in addition to its antitumor action.

PMID- 14729100
TI  - Evidence for a role of human organic anion transporters in the muscular side
      effects of HMG-CoA reductase inhibitors.
AB  - The purpose of this study was to elucidate the role of human organic anion
      transporters (human OATs) in the induction of drug-induced skeletal muscle
      abnormalities. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors have been clinically used for lowering plasma cholesterol levels, and
      are known to induce various forms of skeletal muscle abnormalities including
      myopathy and rhabdomyolysis. Immunohistochemical analysis revealed that human
      OAT1 and human OAT3 are localized in the cytoplasmic membrane of the human
      skeletal muscles. The activities of human OATs were measured using mouse cell
      lines from renal proximal tubules stably expressing human OATs. Human OAT3, but
      not human OAT1, mediates the transport of pravastatin. Fluvastatin inhibited
      organic anion uptake mediated by human OAT1 in a mixture of competitive and
      noncompetitive manner, whereas simvastatin and fluvastatin noncompetitively
      inhibited the organic anion uptake mediated by human OAT3. In conclusion, the
      organic anion transporters OAT1 and OAT3 are localized in the cytoplasmic
      membrane of human skeletal muscles. Pravastatin, simvasatin, and fluvasatin
      inhibit human OATs activity. These results suggest that muscle organic anion
      transporters play a role in the muscular side effects of HMG-CoA reductase
      inhibitors.

PMID- 14729101
TI  - Mesaconitine-induced relaxation in rat aorta: role of Na+/Ca2+ exchangers in
      endothelial cells.
AB  - Previously, we reported that mesaconitine, an aconite alkaloid, increased
      intracellular Ca(2+) concentration ([Ca(2+)](i)) level in endothelium and caused
      relaxation in rat aorta via nitric oxide production. In the present study, we
      investigated the mechanisms of increase in the [Ca(2+)](i) level induced by
      mesaconitine in rat aorta and in human umbilical vein endothelial cells (HUVECs).
      Treatment with the low Na(+) buffer delayed the 30 microM mesaconitine-, but not
      10 microM acetylcholine-, induced relaxation in rat aorta. Treatments with an
      inhibitor of Na(+)/Ca(2+) exchangers (20 microM 3',4'-dichlorobenzamil) and a
      reversed mode (Ca(2+) influx) inhibitor of the exchangers (30 microM 2-[2-[4-(4
      nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate, KBR7943) showed similar
      effects. In HUVECs, 30 microM mesaconitine increased the [Ca(2+)](i) level in the
      presence of extracellular CaCl(2) and NaCl, and the response was inhibited by
      KBR7943. Mesaconitine increased intracellular Na(+) concentration level in
      HUVECs. The [Ca(2+)](i) response by mesaconitine was inhibited by 100 microM D
      tubocurarine (an inhibitor of nicotinic acetylcholine receptors), but was not
      inhibited in the glucose-free buffer and by inhibitors of Na(+)/H(+) exchangers.
      These findings suggest that mesaconitine stimulated Ca(2+) influx via the
      Na(+)/Ca(2+) exchangers in endothelial cells and caused relaxation in the aorta.
      The possibility of D-tubocurarine-sensitive Na(+) channels as target(s) of
      mesaconitine is discussed.

PMID- 14729102
TI  - Selected amino acids, dipeptides and arylalkylamine derivatives do not act as
      allosteric modulators at GABAB receptors.
AB  - Based on recent reports describing enhancing actions of arylalkylamines
      (fendiline [N-(3,3-diphenylpropyl)-alpha-methylbenzylamine] and prenylamine [N
      (3,3-diphenylpropyl)-alpha-methylphenethylamine]), amino acids (L-phenylalanine,
      L-leucine and L-isoleucine), and dipeptides (L-Phe-Phe and L-Phe-Leu) on baclofen
      induced responses in cortical slices, we have examined whether these compounds
      might act as positive allosteric modulators at GABA(B) receptors. Unlike the
      previously described allosteric GABA(B) receptor modulator CGP7930 (2,6-Di-tert
      butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol), these compounds did not enhance
      GABA(B) receptor-mediated guanosine 5'-O-(3-thiotriphosphate) [GTP(gamma)35S]
      binding in native or recombinant cell membrane preparations. Similarly, in a
      competition binding assay using the antagonist radioligand [3H]CGP62349, CGP7930,
      but not the other compounds, enhanced the affinities of gamma-aminobutyric acid
      (GABA) for native GABA(B) receptors from rat brain cortex. Finally, in a cellular
      assay (Ca(2+) signaling in a recombinant cell line), CGP7930 was again the only
      compound found to enhance the GABA response. It is concluded that the
      arylalkylamines, amino acids and dipeptides tested do not act as allosteric
      modulators at native and recombinant GABA(B) receptors.

PMID- 14729103
TI  - Differential regulation of K+ and Ca2+ channel gene expression by chronic
      treatment with estrogen and tamoxifen in rat aorta.
AB  - The beneficial effect of estrogen on the vascular system is partly associated
      with its ability to reduce vascular contractility. Estrogen acutely activates
      large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) and inhibits L-type
      voltage-gated Ca(2+) channel (VGCC) in vascular smooth muscle cells. However, a
      long-term influence of estrogen, estrogen deficiency, or selective estrogen
      receptor modulators on gene expression of these ion channels is unclear. This
      study was therefore aimed to determine the relative mRNA expression levels of
      alpha- and beta-subunits of BK(Ca), K(V)1.5 subtype of delayed rectifier K(+)
      channel (K(V)), and alpha(1C) subunit of L-type VGCC in endothelium-denuded
      aortas from female rats by a semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR) analysis. Rats were divided into four experimental
      groups: (i) sham-operated control, (ii) ovariectomized, (iii) ovariectomized with
      17 beta-estradiol treatment and (iv) ovariectomized with tamoxifen treatment. The
      results showed that ovariectomy decreased the mRNA expression of K(V)1.5 while it
      increased the mRNA expression of alpha(1C) subunit of L-type VGCC. Ovariectomy
      induced modulation of gene expression of these ion channels was completely
      prevented in ovariectomized rats receiving chronic treatment with estrogen or
      tamoxifen. In contrast, the expression levels of genes encoding both alpha- and
      beta-subunits of BK(Ca) remained the same in the four animal groups. The present
      study has provided the first line of evidence suggesting the long-term beneficial
      effects of estrogen and tamoxifen therapy on vascular ion channel expressions,
      which may be an important mechanism by which the favorable modulation of vessel
      tone by estrogen or selective estrogen receptor modulators is mediated.

PMID- 14729104
TI  - Activation of ERK1/2, JNK and PKB by hydrogen peroxide in human SH-SY5Y
      neuroblastoma cells: role of ERK1/2 in H2O2-induced cell death.
AB  - Reactive oxygen species including H(2)O(2) activate an array of intracellular
      signalling cascades that are closely associated with cell death and cell survival
      pathways. The human neuroblastoma SH-SY5Y cell line is widely used as model cell
      system for studying neuronal cell death induced by oxidative stress. However, at
      present very little is known about the signalling pathways activated by H(2)O(2)
      in SH-SY5Y cells. Therefore, in this study we have investigated the effect of
      H(2)O(2) on extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal
      kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase
      B (PKB) activation in undifferentiated and differentiated SH-SY5Y cells. H(2)O(2)
      stimulated time and concentration increases in ERK1/2, JNK and PKB
      phosphorylation in undifferentiated and differentiated SH-SY5Y cells. No
      increases in p38 MAPK phosphorylation were observed following H(2)O(2) treatment.
      The phosphatidylinositol 3-kinase (PI-3K) inhibitors wortmannin and LY 294002 ((2
      (4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) inhibited H(2)O(2)-induced
      increases in ERK1/2 and PKB phosphorylation. Furthermore, H(2)O(2)-mediated
      increases in ERK1/2 activation were sensitive to the MAPK kinase 1 (MEK1)
      inhibitor PD 98059 (2'-amino-3'-methoxyflavone), whereas JNK responses were
      blocked by the JNK inhibitor SP 600125 (anthra[1-9-cd]pyrazol-6(2H)-one).
      Treatment of SH-SY5Y cells with H(2)O(2) (1 mM; 16 h) significantly increased the
      release of lactate dehydrogenase (LDH) into the culture medium indicative of a
      decrease in cell viability. Pre-treatment with wortmannin, SP 600125 or SB 203580
      (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole; p38
      MAPK inhibitor) had no effect on H(2)O(2)-induced LDH release from
      undifferentiated or differentiated SH-SY5Y cells. In contrast, PD 98059 and LY
      294002 significantly decreased H(2)O(2)-induced cell death in both
      undifferentiated and differentiated SH-SY5Y cells. In conclusion, we have shown
      that H(2)O(2) stimulates robust increases in ERK1/2, JNK and PKB in
      undifferentiated and differentiated SH-SY5Y cells. Furthermore, the data
      presented clearly suggest that inhibition of the ERK1/2 pathway protects SH-SY5Y
      cells from H(2)O(2)-induced cell death.

PMID- 14729105
TI  - Heterodimerization and cross-desensitization between the mu-opioid receptor and
      the chemokine CCR5 receptor.
AB  - Cross-desensitization between micro-opioid receptor agonists and CC chemokines
      was shown to occur in immune cells and in the central nervous system. However,
      these cells do not permit examination of potential mechanisms at cellular levels
      due to low levels and mixed populations of receptors. In this study, we
      investigated possible interactions and biochemical mechanisms of cross
      desensitization between the mu-opioid and chemokine CCR5 receptors coexpressed in
      Chinese hamster ovary (CHO) cells. Hemagglutinin (HA)-tagged micro-opioid
      receptor coimmunoprecipitated with FLAG (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys)-tagged
      chemokine receptor CCR5 in cells expressing the two receptors, but not in a
      mixture of cells transfected with one of the two receptors, indicating that the
      two receptors form heterodimers. Treatment with the mu-opioid receptor agonist
      DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin), the chemokine RANTES
      (Regulated on Activation, Normal T cell-Expressed and -Secreted) (CCL5), or both,
      did not affect the level of coimmunoprecipitation. DAMGO and RANTES (CCL5)
      induced chemotaxis in CHO cells coexpressing both receptors, and preincubation
      with either DAMGO or RANTES (CCL5) profoundly inhibited chemotaxis caused by the
      other. DAMGO pretreatment enhanced phosphorylation of the chemokine CCR5 receptor
      and reduced RANTES (CCL5)-promoted [35S]GTP gamma S binding. Conversely, RANTES
      (CCL5) preincubation slightly increased phosphorylation of the mu-opioid receptor
      and significantly reduced DAMGO-induced [35S]GTP gamma S binding. These results
      indicate that activation of either receptor affected G protein coupling of the
      other, likely due to enhanced phosphorylation of the receptor. Heterodimerization
      between the two receptors may contribute to the observed cross-desensitization.

PMID- 14729106
TI  - Antiplatelet effects of KW-7, a new inhibitor of cyclic nucleotide
      phosphodiesterases.
AB  - The antiplatelet effect of a new synthetic compound, 8,9-dimethoxyl-1-(4-methoxy
      phenyl)-5,6-dihydro-pyrrolo[2,1-a]isoquinoline-2,3-dione (KW-7), was determined
      in rabbit platelets. KW-7 concentration-dependently prevented platelet
      aggregation caused by arachidonic acid, collagen, platelet-activating factor, and
      thrombin. KW-7 induced a substantial increase in cyclic AMP levels and a smaller
      increase in cyclic GMP levels in platelets. In platelet homogenates, KW-7
      inhibited both cyclic AMP- and cyclic GMP-phosphodiesterase activities. The
      antiplatelet effect of KW-7 was reversed by SQ22536 (an inhibitor of adenylate
      cyclase) and H89 (an inhibitor of protein kinase A) but not by ODQ (an inhibitor
      of soluble guanylate cyclase). These data suggest that the antiplatelet effect of
      KW-7 is cyclic AMP-dependent, and is through inhibition of platelet
      phosphodiesterases. In addition, KW-7 inhibited arachidonic acid-stimulated
      thromboxane production; this effect was associated with an increase in
      prostaglandin D(2) levels indicating KW-7 is also an inhibitor of thromboxane
      synthase. The dual inhibition of KW-7 on phosphodiesterase and thromboxane
      synthase might provide an attractive target in developing antiplatelet drugs.

PMID- 14729107
TI  - Characterization of human urinary bladder KATP channels containing SUR2B splice
      variants expressed in L-cells.
AB  - The molecular properties of the sulfonylurea receptor 2 (SUR2) subunits of K(ATP)
      channels expressed in urinary bladder were assessed by polymerase chain reaction
      (PCR). This showed that SUR2B exon 17- mRNA (72%) was predominant over the SUR2B
      exon 17+ splice variant (28%). The pharmacological properties of both of these
      isoforms stably expressed in mouse Ltk(-)cells (L-cells) with K(IR) 6.2 were
      determined by measuring changes in membrane potential responses evoked by K(+)
      channel openers using bis-(1,3-dibutylbarbituric acid) trimethine oxonol
      (DiBAC(4)(3)) fluorescence. The rank order potency of a variety of structurally
      distinct K(+) channel openers was found to be the same in both stable cell lines
      and compared well with guinea pig bladder cells. The potency of these compounds
      in the SUR2B exon 17- cells more closely resembled the potency measured in guinea
      pig bladder unlike the cell line containing the SUR2B exon 17+ subtype. Analysis
      of the displacement of [125I]A-312110 binding with the same K(+) channel openers
      to the SUR2B exon 17- cells showed excellent correlation to those measured in
      guinea pig bladder. This study supports the notion that K(ATP) channels
      containing SUR2B exon 17- represent a major splice variant expressed in urinary
      bladder smooth muscle.

PMID- 14729108
TI  - Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1
      mRNA inhibits neointima formation in rat carotid artery after balloon injury.
AB  - We designed and synthesized a chimeric DNA-RNA hammerhead ribozyme targeting
      transforming growth factor (TGF)-beta 1 mRNA and found that this ribozyme
      effectively and specifically inhibited growth of vascular smooth muscle cells. We
      examined the effects of the chimeric DNA-RNA hammerhead ribozyme targeting TGF
      beta 1 mRNA on neointima formation and investigated the underlying mechanism to
      develop a possible gene therapy for coronary artery restenosis after percutaneous
      transluminal coronary angioplasty. Expression of mRNAs encoding TGF-beta 1,
      p27kip1, and connective tissue growth factor (CTGF) in carotid artery increased
      after balloon injury. Fluorescein-isothiocyanate (FITC)-labeled ribozyme was
      taken up into the midlayer smooth muscle of the injured carotid artery. Both 2
      and 5 mg of ribozyme reduced neointima formation by 65% compared to that of
      controls. Ribozyme markedly decreased expression of TGF-beta 1 mRNA and protein
      in injured vessel. Mismatch ribozyme had no effect on expression of TGF-beta 1
      mRNA protein in injured vessel. Ribozyme markedly decreased expression of
      fibronectin, p27kip1, and CTGF mRNAs in injured vessel, whereas a mismatch
      ribozyme had no effect on these mRNAs. These findings indicate that the chimeric
      DNA-RNA hammerhead ribozyme targeting TGF-beta 1 mRNA inhibits neointima
      formation in rat carotid artery after balloon injury with suppression of TGF-beta
      1 and inhibition of extracellular matrix and CTGF. In conclusion, the hammerhead
      ribozyme against TGF-beta 1 may have promise as a therapy for coronary artery
      restenosis after percutaneous transluminal coronary angioplasty.

PMID- 14729109
TI  - Effect of ethanol on the electrophysiological characteristics of pulmonary vein
      cardiomyocytes.
AB  - Ethanol consumption has been considered to contribute to the occurrences of
      paroxysmal atrial fibrillation. Pulmonary veins are known to initiate atrial
      fibrillation. This study investigated whether ethanol may induce atrial
      fibrillation through increasing arrhythmogenic activity of pulmonary vein
      cardiomyocytes. Using the whole-cell clamp technique, the action potential and
      ionic currents were investigated in rabbit single pulmonary vein beating
      cardiomyocytes with and without (control) incubation of ethanol. Compared with
      control cardiomyocytes, pulmonary vein cardiomyocytes receiving 0.3 mg/ml or 1
      mg/ml ethanol had shorter action potential duration, but had similar beating
      rates (2.6+/-1.3, 2.7+/-1.2, 2.7+/-1.2 Hz) and incidences (45%, 41%, 32%) of
      delayed after depolarization. Pulmonary vein cardiomyocytes receiving ethanol had
      smaller L-type Ca(2+) currents and larger transient outward currents, but had
      similar transient inward, delayed rectified outward, inward rectified and
      pacemaker currents. These results suggest that ethanol has no direct effect on
      the arrhythmogenic potential of pulmonary vein cardiomyocytes.

PMID- 14729110
TI  - Inhibition of the vascular-endothelial growth factor-induced intracellular
      signaling and mitogenesis of human endothelial cells by epigallocatechin-3
      gallate.
AB  - Galloyl group-containing catechins, such as epigallocatechin-3 gallate, inhibit
      receptor tyrosine kinase activity of several growth factor receptors. This study
      investigated the effects of epigallocatechin-3 gallate, as compared to
      epicatechin, on vascular endothelial growth factor-induced intracellular
      signaling and mitogenesis of human umbilical endothelial cells. Epigallocatechin
      3 gallate concentration-dependently inhibited vascular endothelial growth factor
      induced DNA synthesis, cell proliferation, autophosphorylation of vascular
      endothelial growth factor receptors-1 and -2, phosphorylation of extracellular
      signal-regulated kinases-1 and -2, and mRNA expression of the early growth
      response factor-1. In contrast, epicatechin was not effective. Thus,
      epigallocatechin-3 gallate may be an attractive candidate drug to inhibit tumour
      angiogenesis.

PMID- 14729111
TI  - Vinburnine decelerates [3H]N-methylscopolamine binding to recombinant human
      muscarinic M1-M4 acetylcholine receptors.
AB  - The kinetics of [3H]N-methylscopolamine binding to membranes of Chinese hamster
      ovary (CHO) cells expressing muscarinic M(1)-M(4) acetylcholine receptors was
      studied. [3H]N-methylscopolamine dissociation was used for the "single-point"
      analysis of allosteric modulation by vinburnine (L-eburnamonine). [3H]N
      methylscopolamine dissociation was decelerated by vinburnine with EC(50) values
      of 29.5, 4.1, 9.5 and 15.0 microM for muscarinic M(1)-M(4) receptors,
      respectively. Acetylcholine doubled the EC(50) of vinburnine for muscarinic M(3)
      receptors. These kinetic EC(50) values correlated with equilibrium binding
      constants, supporting the ternary allosteric model. Vinburnine also decelerated
      the association of [3H]N-methylscopolamine binding, resulting in opposite
      cooperativity for muscarinic M(1) and M(2) receptors.

PMID- 14729112
TI  - Evidence for participation of GABA(A) receptors in a rat model of secondary
      hyperalgesia.
AB  - We investigated the involvement of endogenous gamma-aminobutyric acid (GABA) in
      the modulation of secondary hyperalgesia induced by intraplantar (i.pl.)
      injection of 5% formalin in the rat tail-flick test. Intraplantar injection of
      gabamimetic drugs such as gabapentin (150-600 microg/site) or phenobarbital (20
      80 microg/site) reversed secondary hyperalgesia, as measured by an increase in
      the tail-flick latency, thus displaying a peripheral antihyperalgesic effect.
      Central inhibition of the secondary hyperalgesia response by gabapentin was
      obtained following injection of either 200 microg intrathecally (i.t.) or 50 mg
      intraperitoneally (i.p.). The effects induced by gabamimetics were blocked
      locally or centrally by prior treatment with the specific GABA(A) receptor
      antagonist, bicuculline (80 ng/paw or 20 ng, i.t.). These data indicate the
      participation of endogenous GABA in the modulation of secondary hyperalgesia,
      through either a peripheral and/or a central action. They also indicate that
      GABA(A) receptors might be involved since a specific antagonist of these
      receptors (bicuculline) blocked this response.

PMID- 14729113
TI  - Evidence for a central mechanism of action of S-(+)-ketoprofen.
AB  - It has been observed that some non-steroidal anti-inflammatory drugs (NSAIDs) may
      act through several mechanisms, in addition to central inhibition of
      prostaglandin synthesis. These other mechanisms include the L-arginine-nitric
      oxide (L-arginine-NO) pathway, as well as endogenous opiate and serotonergic
      mechanisms. Some of these mechanisms can explain the efficacy of NSAIDs in
      chronic pain conditions such as rheumatoid arthritis. The present study was
      designed to elucidate the involvement of the above pathways/mechanisms in the
      antinociceptive effect of S-(+)-ketoprofen at supraspinal and spinal levels. S
      (+)-ketoprofen induced dose-dependent antinociception in the pain-induced
      functional impairment model in the rat. The antinociceptive effect of S-(+)
      ketoprofen was not altered by i.t. or intracerebroventricula (i.c.v.) pre
      treatment with L-arginine (29.6 microg/site) and L-nitro-arginine-monomethylester
      (L-NAME) (21.1 microg/site) and neither was the effect of S-(+)-ketoprofen
      modified by the opiate antagonist, naloxone (1 mg/kg, s.c.). In marked contrast,
      both i.c.v. administration of the 5-hydroxytryptamine (5-HT)(1)/5-HT(2)/5-HT(7)
      receptor antagonist, methiothepin (1.5 microg/site), and i.t. administration of
      the 5-HT(3)/5-HT(4) receptor antagonist, tropisetron (0.9 microg/site),
      significantly inhibited the S-(+)-ketoprofen-induced antinociceptive effect.
      These data suggest that the antinociceptive response to S-(+)-ketoprofen involves
      serotoninergic mechanisms via both supraspinal 5-HT(1)/5-HT(2)/5-HT(7) receptors
      and 5-HT(3) receptors located at spinal level. A role of the L-arginine-NO and
      opiate systems in S-(+)-ketoprofen-induced antinociception in the pain-induced
      functional impairment model in the rat model seems unlikely.

PMID- 14729114
TI  - Neurochemical changes of the extracellular concentrations of glutamate and
      aspartate in the nucleus accumbens of rats after chronic administration of
      morphine.
AB  - The effects of discontinuing a chronic morphine treatment on the concentrations
      of glutamate and aspartate were analyzed in the nucleus accumbens of unrestrained
      unanesthetized rats. The administration of naloxone or the cessation of morphine
      administration resulted in increased concentrations of glutamate and aspartate in
      this central nervous system area. These increased amino acid concentrations were
      observed a few minutes after naloxone administration and persisted in the
      controls 48 h after the last dose of the opiate. Morphine withdrawal was also
      studied in rats not injected with naloxone. In these latter animals, increased
      concentrations of glutamate and aspartate persisted in controls 96 h after the
      last dose of the opiate. Single doses of morphine, acamprosate or riluzole
      administered to rats previously withdrawn from chronic morphine treatment
      restored the amino acid concentrations to normal levels. These results suggest
      that the maintenance of increased levels of amino acids could be the expression
      of new adjustments in central nervous system neurotransmission after
      discontinuation of the chronic morphine treatment.

PMID- 14729115
TI  - Biphasic modulation by nitric oxide of caspase activation due to malonate
      injection in rat striatum.
AB  - The present study examined caspase activation and its modulation by nitric oxide
      (NO) in a model of oxidative stress induced by injection of malonate (3
      micromol), a mitochondrial toxin, into rat striatum. Caspase-3-like enzymatic
      activity was maximal 6 h after malonate while NO production evaluated by its
      metabolites nitrites and nitrates was increased at 3 h. The neuronal NO-synthase
      inhibitor 7-nitroindazole reduced malonate induced-NO production by 50% at 25
      mg/kg and enhanced by 32% caspase activation. This result suggests that a
      moderate production of NO potentiates caspase activation, an effect
      counterbalanced by NO itself at higher concentrations. Accordingly, complete
      inhibition of NO production by 7-nitroindazole at 50 mg/kg did not modify
      malonate-induced caspase activity. Thus NO production by the neuronal isoform of
      NO-synthase is not the major event leading to caspase activation due to malonate.
      However, NO seems to have pro- and anti-caspase effects that neutralize each
      other.

PMID- 14729116
TI  - Patterns of serotonin- and 2-methylserotonin-induced pain may reflect 5-HT3
      receptor sensitization.
AB  - Intraperitoneal injection of serotonin (5-HT; 0.5-4.0 mg/kg) produced dose
      dependent nociceptive writhing responses, attenuated at all doses by pre
      administration of tropisetron (1.0 mg/kg, i.p.). Administration of 2
      methylserotonin (2-methyl-5-HT) alone was ineffective in inducing writhing. The
      effects of 5-HT (0.5 mg/kg, i.p.) were increased by subsequent injection of 2
      methyl-5-HT (0.5-4.0 mg/kg, i.p.). The enhanced nociceptive responses produced by
      low dose of 5-HT and subsequently administered 2-methyl-5-HT were attenuated by
      pretreatment with tropisetron. These results suggest that the inflammatory
      cascade produced by peripheral administration of 5-HT evokes nociception by
      stimulating visceral 5-HT(3) receptors and that 5-HT-induced mechanisms appear to
      sensitize the 5-HT(3) receptor to subsequent pharmacologic activation.

PMID- 14729117
TI  - Cognitive side effects in rats caused by pharmacological agents used to prevent
      soman-induced lethality.
AB  - It is important that prophylactics used to protect military and emergency
      personnel against lethal doses of nerve agents do not by themselves produce
      impairment of cognitive capability. The purpose of the present study was to
      examine whether physostigmine, scopolamine, and various doses of procyclidine
      might reduce rats' innate preference for novelty. When these drugs were tested
      separately, the results showed that physostigmine (0.1 mg/kg) and procyclidine (3
      mg/kg) did not affect preference for novelty, whereas scopolamine (0.15 mg/kg)
      and procyclidine in a higher dose (6 mg/kg) resulted in a preference deficit
      (Experiment 1). In Experiment 2, the combination of physostigmine and scopolamine
      or physostigmine and procyclidine (6 mg/kg) caused a marked deficit in preference
      for novelty. A much milder deficit was observed when physostigmine was combined
      with lower doses (1 or 3 mg/kg) of procyclidine. The latter combinations also had
      milder adverse impact on the animals' interest in the test environment and
      activity measures than the former combinations. By combining physostigmine with
      anticholinergics, a potentiation of adverse effects on behavior was seen. It is
      concluded that a slight cognitive impairment might be unavoidable with effective
      prophylactics.

PMID- 14729118
TI  - The self-administration of WIN 35,428 and cocaine: comparisons of satiety
      threshold and elimination half-life in rats.
AB  - Rats that self-administered cocaine at unit doses between 0.75 and 12 micromol/kg
      with mean inter-injection intervals between approximately 2 and 18 min also
      reliably self-administered the cocaine analogue WIN 35,428 (beta-CFT; (-)-3 beta
      (4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester) at unit doses
      between 0.1 and 1.6 micromol/kg with mean intervals between 10 and 116 min. The
      long inter-injection intervals of WIN 35,428 necessitated sessions of more than
      12 h. The inter-injection intervals were regular and proportional to the unit
      dose, consistent with the satiety threshold model. Analysis of the mean intervals
      as a function of unit doses generated values for the mean satiety threshold of
      cocaine and WIN 35,428 of 6.10 and 0.87 micromol/kg, respectively. The mean
      t(1/2) for cocaine and WIN 35,428 were 11.1 and 69.4 min, respectively. The
      approximately 43-fold lower rate of consumption of WIN 35,428 relative to cocaine
      was a product of the seven-fold greater pharmacodynamic potency and the six-fold
      greater pharmacokinetic potency.

PMID- 14729119
TI  - Neuroleptic-like effects of gamma-hydroxybutyrate: interactions with haloperidol
      and dizocilpine.
AB  - gamma-Hydroxybutyrate (GHB) is a drug of abuse with multiple mechanisms of
      action. Consistent with its ability to modulate dopaminergic systems, GHB
      reportedly shares behavioral effects with neuroleptics and interacts with them in
      a synergistic manner. Here, we examined the ability of GHB and haloperidol to
      induce catalepsy and to affect operant responding. When given alone, both
      compounds induced catalepsy and decreased response rate. When given together,
      however, they produced these effects in an additive manner. This is further
      evidence that GHB has neuroleptic-like effects, but suggests that GHB interacts
      additively, not synergistically, with neuroleptics. The mechanisms involved in
      GHB- and haloperidol-induced catalepsy are different because the N-methyl-D
      aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), attenuated the
      cataleptic effects of haloperidol, but enhanced those of GHB. The latter finding
      suggests that other NMDA receptor antagonists (e.g., the drugs of abuse-
      phencyclidine and ketamine) may also interact synergistically with GHB.

PMID- 14729120
TI  - Calcitonin gene-related peptide-induced suppression of atrial natriuretic peptide
      release through receptors for CGRP1 but not for calcitonin and amylin.
AB  - Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in
      the central nervous system as well as in the heart. CGRP shows high sequence
      homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to
      investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic
      peptide (ANP) release by using isolated perfused beating left atria and to
      identify its receptor subtypes. Rat alpha-CGRP (0.1, 1, 10, or 100 nM) increased
      atrial contractility and suppressed the release of ANP in a concentration
      dependent manner. However, cys-CGRP (1 microM), a CGRP(2) receptor agonist,
      slightly decreased ANP release without positive inotropism. Human alpha-CGRP (1
      nM) showed an effect on ANP release similar to that of rat alpha-CGRP with potent
      positive inotropism. However, salmon and rat calcitonin (1 microM) caused a
      slight decrease or no change in ANP release. Pretreatment with a receptor
      antagonist for CGRP(1) [rat alpha-CGRP-(8-37)] blocked rat alpha-CGRP-induced
      suppression of ANP release and positive inotropism, whereas the antagonists for
      salmon or amylin did not. Therefore, we suggest that rat alpha-CGRP causes a
      suppression of ANP release with positive inotropism through the receptor for
      CGRP(1) but not that for calcitonin and amylin.

PMID- 14729121
TI  - In vitro opioid activity profiles of 6-amino acid substituted derivatives of 14-O
      methyloxymorphone.
AB  - A series of 6-amino acid conjugates (glycine, alanine and phenylalanine) of the
      highly potent opioid analgesic 14-O-methyloxymorphone was developed in an effort
      to obtain agonists that would have potentially limited ability to cross the blood
      brain barrier. Binding studies revealed that all derivatives displayed high
      affinities (0.77-2.58 nM) at the mu-opioid receptor in rat brain membranes. They
      were potent agonists in mouse vas deferens preparation (IC(50)=5.52-26.8 nM).
      While the alpha-amino acid epimers are favoured by mu-opioid receptors, the beta
      epimers proved to have increased interaction with delta-sites. Only the beta
      phenylalanine conjugate showed some preference for delta- over mu-opioid
      receptors and delta-opioid receptor agonist activity. The relatively high delta
      opioid receptor affinity of this analogue was also predicted by molecular
      modelling studies. The newly developed ionizable derivatives could find clinical
      applications as potent analgesics without the adverse actions of centrally acting
      opioids.

PMID- 14729122
TI  - The effect of cocaine sensitization on mouse immunoreactivity.
AB  - Recent studies indicate a role of the immune system in the behavioral effects of
      cocaine in rodents. In the present study, we attempted to find a correlation
      between the behavioral changes induced by repeated, intermittent administration
      of cocaine and some immunological consequences of sensitization to cocaine. Male
      Albino Swiss mice were treated repeatedly (for 5 days) with cocaine (10 or 15
      mg/kg, intraperitoneally, ip). On day 9, they received a challenge dose of
      cocaine (10 or 15 mg/kg). Acute administration of cocaine increased the locomotor
      activity of mice. In animals treated repeatedly with the higher dose of cocaine,
      the locomotor hyperactivity induced by a challenge dose of the psychostimulant
      (15 mg/kg) was ca. twice as high as that after its first administration; in
      consequence, evidence for behavioral sensitization was obtained. Immune functions
      were evaluated by measuring the ability of splenocytes to proliferate and to
      produce cytokines such as interferon-gamma (IFN-gamma), interleukin (IL)-4 and IL
      10. Acute cocaine administration significantly decreased proliferation of
      splenocytes to concanavalin A (Con A) and increased their ability to produce IFN
      gamma. Repeated intermittent treatment with cocaine in a dose of 10 mg/kg
      significantly decreased the thymus weight and the proliferative response of T
      cells to a suboptimal dose of Con A. Sensitization with the higher dose of
      cocaine significantly enhanced IFN-gamma production. These data indicate that
      cocaine sensitization results in the development of a tolerant state to the
      cocaine-induced suppression of a thymus dependent T-lymphocyte response. It may
      be suggested that the cocaine sensitization partly depends on the altered balance
      of cytokine production, e.g. an increase in IFN-gamma production. Since repeated,
      intermittent use of cocaine by humans leads to psychoses or craving for this
      drug, our findings also seem to indicate considerable importance of monitoring
      and correcting immune changes in the therapy of cocaine addiction.

PMID- 14729123
TI  - Effect of nitric oxide releasing paracetamol and flurbiprofen on cytokine
      production in human blood.
AB  - Exposure of anti-coagulated human blood to Escherichia coli lipopolysaccharide
      (50 ng/ml) resulted in the time-dependent (maximum at 5 h) biosynthesis of
      interleukin-1beta and tumour necrosis factor-alpha (TNF-alpha). Preincubation
      with nitroparacetamol or nitroflurbiprofen (but not paracetamol or flurbiprofen)
      caused dose-related inhibition of the formation of interleukin 1 beta (IC(50)s,
      44.5 and 362 microM, n=12) and tumour necrosis factor-alpha (IC(50)s, 9.0 and
      0.0009 microM, n=12). The inhibitory effect of nitroparacetamol was completely
      reversed by (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; 2
      (4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide
      potassium (carboxy-PTIO, 100 microM; NO scavenging agent). Neither the nuclear
      factor-kappaB transduction inhibitor, pyrrolidinedithiocarbamate (10-1000 microM)
      nor the nitric oxide donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1
      triazene (NOC-5, 10-1000 microM), affected cytokine formation in these
      experiments.

PMID- 14729124
TI  - Protonation effect on drug affinity.
AB  - Pharmacologic ligand-macromolecule interactions are commonly characterized by
      affinity (dissociation) constants such as K(d) or K(i) without regard to the
      protonation effect of the buffer used in the measurement. The protonation effect
      is demonstrated here using isothermal titration microcalorimetry measurements of
      the competitive inhibitor binding of cytidine 2'-monophosphate (2'-CMP) to RNase
      A as a model system in buffers of different ionization Delta H(buffer). The
      results demonstrate the importance of protonation in measures of affinity.

PMID- 14729125
TI  - The structural basis for understanding human brain function and dysfunction.

PMID- 14729126
TI  - Human cholinergic basal forebrain: chemoanatomy and neurologic dysfunction.
AB  - The human cholinergic basal forebrain (CBF) is comprised of magnocellular
      hyperchromic neurons within the septal/diagonal band complex and nucleus basalis
      (NB) of Meynert. CBF neurons provide the major cholinergic innervation to the
      hippocampus, amygdala and neocortex. They play a role in cognition and
      attentional behaviors, and are dysfunctional in Alzheimer's disease (AD). The
      human CBF displays a continuum of large cells that contain various cholinergic
      markers, nerve growth factor (NGF) and its cognate receptors, calbindin,
      glutamate receptors, and the estrogen receptors, ERalpha and ERbeta. Admixed with
      these cholinergic neuronal phenotypes are smaller interneurons containing the m2
      muscarinic acetylcholine receptor (mAChRs), NADPH-diaphorase, GABA, calcium
      binding proteins and several inhibitory neuropeptides including galanin (GAL),
      which is over expressed in AD. Studies using human autopsy material indicate an
      age-related dissociation of calbindin and the glutamate receptor GluR2 within CBF
      neurons, suggesting that these molecules act synergistically to induce
      excitotoxic cell death during aging, and possibly during AD. Choline
      acetyltrasnferease (ChAT) activity and CBF neuron number is preserved in the
      cholinergic basocortical system and up regulated in the septohippocampal system
      during prodromal as compared with end stage AD. In contrast, the number of CBF
      neurons containing NGF receptors is reduced early in the disease process
      suggesting a phenotypic silence and not a frank loss of neurons. In end stage AD,
      there is a selective reduction in trkA mRNA but not p75(NTR) in single CBF cells
      suggesting a neurotrophic defect throughout the progression of AD. These
      observations indicate the complexity of the chemoanatomy of the human CBF and
      suggest that multiple factors play different roles in its dysfunction in aging
      and AD.

PMID- 14729127
TI  - The human cerebellum.
AB  - This short review deals with observations on the gross morphology and internal
      structure of the human cerebellum, and with studies of cerebellar fiber
      connections in non-human primates. Attention is focussed on its gross anatomy,
      the zonal organization of the primate cerebellum, the brain stem, thalamic and
      cortical connections of the cerebellar nuclei and on the cortico-ponto-cerebellar
      pathway. The presence of important reciprocal nucleo-mesencephalo-olivary loops
      as part of the circuitry of the dentate and globose (posterior interposed) nuclei
      and their absence among the connections of other cerebellar nuclei is emphasized.

PMID- 14729128
TI  - Hypothalamus of the human fetus.
AB  - The organization of the human hypothalamus was studied in 31 brains aged from 9
      weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin,
      calbindin, calretinin, neuropeptideY, neurophysin, growth associated protein
      GAP43, synaptophysin and glycoconjugate, 3-fucosyl-N-acetyl-lactosamine.
      Morphogenetic periods 9-10 and 11-14 w.g. are characterized by differentiating
      structures of the lateral hypothalamic zone, which give rise to the lateral
      hypothalamus (LH) and posterior hypothalamus. The perifornical nucleus
      differentiates at 18 w.g., from LH neurons which remain anchored in the
      perifornical position while most of the LH cells are displaced laterally. A
      transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As
      the ventromedial nucleus differentiated at 13-16 w.g., three principal parts; the
      ventrolateral, the dorsomedial and the shell were revealed by distribution of
      calbindin, calretinin and GAP43 immunoreactivity. Morphogenetic periods 15-17, 18
      23 and 24-33 w.g. are characterized by differentiation of the hypothalamic core,
      in which calbindin positive neurons revealed the medial preoptic nucleus at 16
      w.g. abutted laterally by the intermediate nucleus. The dorsomedial nucleus was
      clearly defined at 10 w.g. and consisted of compact and diffuse parts, an
      organization that was lost after 15 w.g. Differentiation of the medial mamillary
      body into lateral and medial was seen at 13-16 w.g. Morphogenetic period after 34
      w.g. was marked by differentiation of midline zone structures including
      suprachiasmatic, arcuate and paraventricular nuclei. The findings of the present
      study provide for a better understanding of the structural organization of the
      adult human hypothalamus, produce new evidence for homologies with the better
      studied rat hypothalamus and underpin staging system for fetal human hypothalamic
      development.

PMID- 14729129
TI  - Novel aspects of the chemical anatomy of the striatum and its efferents
      projections.
AB  - This paper summarizes the results of some of our previous neuroanatomical and
      immunohistochemical studies on the organization of the striatum and its efferent
      projections in rodents, monkeys and humans. It also reports recent functional
      calcium-imaging data obtained in rat brain slices, as well as developmental
      results gathered with bromodeoxyuridine (BrdU) in monkeys. On one hand, single
      axon tracing studies in rats and monkeys have revealed that the majority of
      striatofugal axon arborizes within most striatal target structures. In humans, SP
      positive fibers were found to arborize in the two segments of the globus
      pallidus, where they were closely apposed to pallidal neurons that expressed the
      neurokinin-1 receptor (NK-1r). In agreement with such findings, calcium-imaging
      studies in rats have revealed that pallidal and nigral neurons are both
      responsive to SP. These findings suggest that the striatofugal projection system
      is much more widely distributed than previously thought and exerted a
      multifaceted effect upon its target sites. On the other hand, immunostaining
      studies in humans have shown the presence of several types of putative
      dopaminergic neurons intrinsic to the striatum. Furthermore, BrdU labeling
      experiments in monkeys have demonstrated that new neurons are generated
      throughout adult life in the striatum of normal monkeys and that their number can
      be markedly increased by the administration of neuronal growth factors. These
      findings open new therapeutic avenues for the treatment of neurodegenerative
      disorders that specifically affect the striatum.

PMID- 14729130
TI  - Phenotypic expression of monoamines and GABA in the early development of human
      telencephalon, transient or not transient.
AB  - We review the phenotypic expression of molecules involved in monoamine and GABA
      neurotransmission in the developing human brain. Recent experimental reports have
      analyzed neurotransmitter signaling before the onset of synaptogenesis, which
      could act to influence early developmental events such as proliferation,
      migration, and differentiation of animal brain development. Such signaling may
      also occur in human development. The expression of molecules involved in
      neurotransmission in precocious human brain may reflect either the
      differentiation of a permanent neurotransmitter system of the adult brain or
      transient expression to serve specific developmental functions different from
      those in the adult brain. We review the changes observed in the expression of
      various catecholamine markers such as tyrosine-hydroxylase (TH) immunoreactivity
      in various neuronal populations of the developing human telencephalon. The
      specific transporter for serotonin, serotonin transporter (SERT) has been
      detected in fibers of the internal capsule (IC) during the restricted time period
      of 12-14 gestational weeks in humans. These serotonin-containing fibers do not
      correspond to serotoninergic ascending axons from the raphe nuclei. They may be
      the human counterpart of the thalamo-cortical axons that have been shown to
      uptake serotonin during the critical period of development of the sensory systems
      in rodents. GABA phenotypes are expressed in numerous cells of the human
      ganglionic eminence (GE) and cerebral wall at the end of the embryonic period
      proper. These results are similar to that described at comparable developmental
      stages in the mouse and support the hypothesis of an early migration from
      ganglionic progenitors in humans. But one cannot exclude a transient expression
      of GABA within the post-mitotic neurons, which could influence early
      developmental events. In conclusion, data showing the phenotypic expression of
      molecules in discrete areas of the brain at various points in the protracted
      human development require careful interpretation.

PMID- 14729131
TI  - The nucleus accumbens: a target for deep brain stimulation in obsessive
      compulsive- and anxiety-disorders.
AB  - We considered clinical observations in patients with obsessive-compulsive- and
      anxiety-disorders, who underwent bilateral anterior capsulotomy, as well as
      anatomical and pathophysiological findings. Based on these considerations, we
      choose the shell region of the right nucleus accumbens as target for deep brain
      stimulation (DBS) in a pilot-series of four patients with severe obsessive
      compulsive- and anxiety-disorders. Significant reduction in severity of symptoms
      has been achieved in three of four patients treated. Clinical results as well as
      a 15-O-H(2)O-PET study, perfomed in one patient during stimulation, speak in
      favour of the following hypothesis. As a central relay-structure between
      amygdala, basal ganglia, mesolimbic dopaminergic areas, mediodorsal thalamus and
      prefrontal cortex, the accumbens nucleus seems to play a modulatory role in
      information flow from the amygdaloid complex to the latter areas. If disturbed,
      imbalanced information flow from the amygdaloid complex could yield obsessive
      compulsive- and anxiety-disorders, which can be counteracted by blocking the
      information flow within the shell region of the accumbens nucleus by deep brain
      stimulation.

PMID- 14729132
TI  - Cytology of human dorsal midcingulate and supplementary motor cortices.
AB  - Human dorsal midcingulate cortex (MCC) is activated during many cognitive tasks
      and its role in skeletomotor functions is reflected in the size, density, and
      neurofilament proteins (NFP) expressed by neurons in this region. The present
      study used antibodies for neuron-specific nuclear binding protein and NFP in
      three postmortem cases to assess the cytology of the dorsal midcingulate areas
      24c', 24d, and 32' and supplementary motor cortex. Area 24c' has a thin layer Va
      and a Vb with large and NFP+ neurons not present on the gyral surface. Area 24d
      has two divisions; area 24dv on the ventral bank has layer Vb neurons that form
      aggregates, while area 24dd on the dorsal bank has large and solitary layer Vb
      pyramids. Co-registration of each case to standardized coordinates showed that
      the rostral area 24d border is at the vertical plane of the anterior commissure
      and its caudal border with area 23c is -2+/-0.21cm in the y-axis. The transition
      to supplementary motor areas is characterized by significant increases in the
      density of large, NFP expressing neurons in layer IIIc and a substantial
      reduction in the size and density of such neurons in layer V. Since many acute
      pain studies activate dorsal MCC, understanding the architecture of this region
      will help explain its selective vulnerability to chronic pain and stress
      syndromes.

PMID- 14729133
TI  - Postnatal development of calcium-binding proteins immunoreactivity (parvalbumin,
      calbindin, calretinin) in the human entorhinal cortex.
AB  - The entorhinal cortex is an essential component in the organization of the human
      hippocampal formation related to cortical activity. It transfers, neocortical
      information (ultimately distributed to the dentate gyrus and hippocampus) and
      receives most of the hippocampal output directed to neocortex. At birth, the
      human entorhinal cortex presents similar layer organization as in adults,
      although layer II (cell islands) and upper layer III have a protracted
      maturation. The presence of interneurons expressing calcium-binding proteins
      (parvalbumin, calbindin-D28K (calbindin) and calretinin) is well documented in
      the adult human entorhinal cortex. In many of them the calcium binding is co
      localized with GABA. Parvalbumin-immunoreactive cells and fibers were virtually
      absent at birth, their presence increasing gradually in deep layer III, mostly in
      the lateral and caudal portions of the entorhinal cortex from the 5th month
      onwards. Calbindin immunoreactive cells and fibers were present at birth, mainly
      in layers II and upper III; mostly at rostral and lateral portions of the
      entorhinal cortex, increasing in number and extending to deep layers from the 5th
      month onwards. Calretinin immunoreactivity was present at birth, homogeneously
      distributed over layers I, II and upper V, throughout the entorhinal cortex. A
      substantial increase in the number of calretinin neurons in layer V was observed
      at the 5th month. The postnatal development of parvalbumin, calbindin and
      calretinin may have an important role in the functional maturation of the
      entorhinal cortex through the control of hippocampal, cortical and subcortical
      information.

PMID- 14729134
TI  - The primate basal ganglia: parallel and integrative networks.
AB  - The basal ganglia and frontal cortex operate together to execute goal directed
      behaviors. This requires not only the execution of motor plans, but also the
      behaviors that lead to this execution, including emotions and motivation that
      drive behaviors, cognition that organizes and plans the general strategy, motor
      planning, and finally, the execution of that plan. The components of the frontal
      cortex that mediate these behaviors, are reflected in the organization,
      physiology, and connections between areas of frontal cortex and in their
      projections through basal ganglia circuits. This comprises a series of parallel
      pathways. However, this model does not address how information flows between
      circuits thereby developing new learned behaviors (or actions) from a combination
      of inputs from emotional, cognitive, and motor cortical areas. Recent anatomical
      evidence from primates demonstrates that the neuro-networks within basal ganglia
      pathways are in a position to move information across functional circuits. Two
      networks are: the striato-nigral-striatal network and the thalamo-cortical
      thalamic network. Within each of these sets of connected structures, there are
      both reciprocal connections linking up regions associated with similar functions
      and non-reciprocal connections linking up regions that are associated with
      different cortical basal ganglia circuits. Each component of information (from
      limbic to motor outcome) sends both feedback connection, and also a feedforward
      connection, allowing the transfer of information. Information is channeled from
      limbic, to cognitive, to motor circuits. Action decision-making processes are
      thus influenced by motivation and cognitive inputs, allowing the animal to
      respond appropriate to environmental cues.

PMID- 14729135
TI  - The human raphe nuclei and the serotonergic system.
AB  - The raphe nuclei are distributed near the midline of the brainstem along its
      entire rostro-caudal extension. The serotonergic neurons are their main neuronal
      components, although a proportion of them lie in subdivisions of the lateral
      reticular formation. They develop from mesopontine and medullary primordia, and
      the resulting grouping into rostral and caudal clusters is maintained into
      adulthood, and is reflected in the connectivity. Thus, the mesencephalon and
      rostral pons, neurons within the rostral raphe complex (caudal linear, dorsal
      raphe, and median raphe nuclei) project primarily to the forebrain. By contrast,
      in the caudal pons and medulla oblongata, neurons within the caudal raphe complex
      (raphe magnus, raphe obscurus, raphe pallidus nuclei and parts of the adjacent
      lateral reticular formation) project to the brainstem nuclei and to the spinal
      cord. The median raphe and dorsal raphe nuclei provide parallel and overlapping
      projections to many forebrain structures with axon fibers exhibiting distinct
      structural and functional characteristics. The caudal group of the serotonergic
      system projects to the brainstem, and, by three parallel projections, to the
      dorsal, intermediate and ventral columns in the spinal cord. The serotonergic
      axons arborize over large areas comprising functionally diverse targets. Some
      projections form classical chemical synapses while many do not, thus contributing
      to the so-called paracrine or volume transmission. The serotonergic projections
      participate in the regulation of different functional (motor, somatosensory,
      limbic) systems; and have been associated with a wide range of neuropsychiatric
      and neurological disorders. Finally, recent experimental data support the role of
      serotonin in modulating brain development, such that a dysfunction in
      serotonergic transmission during early life could lead to long lasting structural
      and functional alterations.

PMID- 14729136
TI  - Photodynamic inhibition of enzymatic detachment of human cancer cells from a
      substratum.
AB  - Photodynamic therapy (PDT) is currently used for cancer treatment. It is shown
      that sublethal PDT of human WiDr adenocarcinoma cells and D54Mg glioblastoma
      cells with 5-aminolevulinic acid (ALA), disulfonated tetraphenylporphyrine
      (TPPS(2a)), or MitoTracker Red (MTR) inhibits their trypsin-induced detachment
      from a plastic substratum. TPPS(2a) was bound selectively to the plasma membrane,
      whereas MTR was found in mitochondria. Both granular and diffuse fluorescence of
      ALA-derived protoporphyrin IX (PpIX) was observed in the perinuclear cytoplasm
      but not in the plasma membrane of WiDr cells stained for 2 h with 1 mM ALA. In
      D54Mg cells, PpIX fluorescence was observed not only in the cytoplasm but also in
      the plasma membrane. Fluorescence measurements showed a progressive accumulation
      of PpIX in the WiDr cells during incubation with ALA and a PpIX efflux into the
      medium after 1 h or longer incubation. PpIX retained in the plasma membrane
      during efflux may be responsible for PDT-induced impairment of cell adhesion. On
      the other hand, MTR-PDT or ALA-PDT after 15-min incubation, when the newly
      synthesized PpIX should remain in mitochondria, also inhibited enzymatic cell
      detachment. Therefore, photodynamic targeting of mitochondria, remote from the
      cell surface where adhesion occurs, may disturb cell adhesion. Photodynamic
      inhibition of enzymatic cell detachment may be related to PDT-induced inhibition
      of tumour metastasis.

PMID- 14729137
TI  - Protective effect of ascorbate against oxidative stress in the mouse lens.
AB  - The purpose of this study was to determine if high ascorbate of the human aqueous
      protects the lens against oxidative stress. Previous studies with the rat lens
      have been inconclusive because of its fortification with aldose reductase (AR),
      an important antioxidant. The human lens is deficient in this activity. These
      studies were hence done with the mouse lens, a species deficient in this enzyme.
      The reactive oxygen species (ROS)-induced physiological damage to the tissue was
      assessed in organ culture, by measuring its ability to actively transport 86Rb(+)
      ions, in the absence and presence of ascorbate. In addition, the status of tissue
      metabolism and its antioxidant reserve were assessed by quantitating ATP and
      glutathione (GSH). As expected, ROS decreased the membrane transport activity as
      well as the levels of ATP and GSH. Ascorbate minimized these toxic effects
      substantially. The presence of high ascorbate, therefore, appears highly
      beneficial in protecting the lens against oxidative damage and cataract
      formation, despite a deficiency of AR. The findings therefore appear to be
      significant from the point of view of using this nutrient for delaying the onset
      of cataract development in human beings, therapeutically as well as
      nutritionally.

PMID- 14729138
TI  - Enzymatic and nonenzymatic formation of reactive oxygen species from 6-anilino
      5,8-quinolinequinone.
AB  - The nonenzymatic and enzymatic formation of reactive oxygen species (ROS) from
      LY83583 (6-anilino-5,8-quinolinequinone) was investigated by electron
      paramagnetic resonance (EPR) spectroscopy. In the presence of thiol compounds
      such as glutathione and L-cysteine, LY83583 underwent a one-electron reduction
      due to low redox potential (-0.3+/-0.01 V vs. SCE), followed by formation of
      LY83583 semiquinone anion radical. This species was characterized by EPR
      spectroscopy under an argon atmosphere at neutral pH. Under an aerobic condition,
      this species interacts with molecular oxygen to form a superoxide anion radical.
      GSH-conjugated LY83583 was also identified by NMR and FAB-MS. When LY83583 was
      applied to PC12 cells, ROS formation was completely inhibited by both the
      flavoenzyme inhibitor DPI and the DT-diaphorase inhibitor dicumarol. On the other
      hand, ROS generation occurred independent of intracellular GSH level. These
      results indicate that LY83583 can generate ROS both enzymatically and
      nonenzymatically, although the enzymatic formation is dominant over the
      nonenzymatic system in PC12 cells.

PMID- 14729139
TI  - Reactivity of flavonoids with 1-hydroxyethyl radical: a gamma-radiolysis study.
AB  - We have investigated the reactivity between 11 flavonoids and 1-hydroxyethyl
      radical (HER). HER was recently implicated in many liver injuries induced by
      ethanol intoxication. In this study, HER was generated by radiolysis; due to its
      reaction rate, HER is well known to be responsible for solute degradation in
      irradiated ethanol. Flavonoid ethanol solutions were irradiated with gamma-rays
      and the flavonoid degradation was followed by HLPC. We observed the degradation
      of flavonols while all other flavonoids (flavones, flavanones, dihydroflavonols,
      catechins) were not degraded after irradiation. The major radiolysis products
      were identified by NMR and LC-MS and we concluded that flavonols were essentially
      transformed into depsides. We proposed a reactivity mechanism between flavonols
      and HER. In a first step, H-transfer occurred from the 3-OH group to HER.
      Afterwards, C-ring opening occurred due to the presence of the 2,3-double bond in
      flavonols. Finally, we calculated the reaction constants in order to evaluate the
      antioxidant activity of flavonols against HER and to compare it with reference
      compounds.

PMID- 14729140
TI  - Modulation of porphyrin binding to serum albumin by pH.
AB  - In this study, we show that the difference in acidity of functional groups in
      porphyrin photosensitizers provides a meaningful avenue to achieve differential
      localization and retention of porphyrins in tissues and cells, and in the end
      could be a positive factor in the photodynamic treatment of cancer (PDT). We have
      demonstrated that meso-tetraphenylporphyrin derivative with four phosphonate
      (bond P(double bond O)(bond OH)(2)) moieties exists in aqueous solutions mainly
      in four forms that differ by a degree of protonation of the porphyrin ring and
      ionization of the phosphonate group. It is shown that each porphyrin form has
      different affinities toward the model protein (bovine serum albumin, BSA). Thus
      pH of the medium significantly modulates the affinity of the phosphonate
      porphyrin toward BSA. At lower pH (pH 6.0), the phosphonate porphyrin and BSA
      form a complex with affinity constant of K(b)=6.9 x 10(5) M(-1), while at pH 7.0
      the K(b)=6.1 x 10(5) M(-1). At pH 8.0 the association is significantly lower.
      Because cancerous cells have generally lower pH (pH approximately 6.9) compared
      to healthy cells (pH approximately 7.4), the pH of such cells could be a decisive
      factor for cellular retention of the porphyrin in the form of an associate with
      intracellular proteins. Moreover, we have also demonstrated that the
      protonation/deprotonation equilibria do not negatively affect the photophysical
      properties or ability of phosphonate porphyrin to generate singlet oxygen.

PMID- 14729141
TI  - Amino acid transport is down-regulated in ischemic human intestinal epithelial
      cells.
AB  - Amino acid transport across the plasma membrane is essential for supplying
      enterocytes with amino acids for cellular metabolism. We studied amino acid
      transport during ischemic conditions using human intestinal epithelial cell line
      Caco-2. Cells were incubated under nutrient-deprived (phosphate-buffered saline,
      PBS), hypoxic, and ischemic (PBS+hypoxia) conditions. Ischemia resulted in a
      significant decrease in glutamine transport by a mechanism that decreased V(max)
      without affecting K(m). The expression of system ATB degrees (glutamine
      transporter) mRNA decreased in the ischemic and nutrient-deprived groups,
      suggesting that the down-regulation of glutamine transport is due to modification
      of expression of the ATB degrees gene. The transport of glutamate and leucine,
      DNA synthesis, and intracellular glutathione also decreased in the ischemic
      group. These findings throw some light on the mechanism of intestinal epithelial
      damage during ischemia.

PMID- 14729142
TI  - Nuclear localization of tetrahydrobiopterin biosynthetic enzymes.
AB  - Biosynthesis of the tetrahydrobiopterin (BH(4)) cofactor, essential for
      catecholamines and serotonin production and nitric oxide synthase (NOS) activity,
      requires the enzymes GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin
      synthase (PTPS), and sepiapterin reductase (SR). Upon studying the distribution
      of GTPCH and PTPS with polyclonal immune sera in cross sections of rat brain,
      prominent nuclear staining in many neurons was observed besides strong staining
      in peri-ventricular structures. Furthermore, localization studies in transgenic
      mice expressing a Pts-LacZ gene fusion containing the N-terminal 35 amino acids
      of PTPS revealed beta-galactosidase in the nucleus of neurons. In contrast, PTPS
      beta-galactosidase was exclusively cytoplasmic in the convoluted kidney tubules
      but nuclear in other parts of the nephron, indicating again that nuclear
      targeting may occur only in specific cell categories. Furthermore, the N terminus
      of PTPS acts as a domain able to target the PTPS-beta-galactosidase fusion
      protein to the nucleus. In transiently transfected COS-1 cells, which do not
      express GTPCH and PTPS endogenously, we found cytoplasmic and nuclear staining
      for GTPCH and PTPS. To further investigate nuclear localization of all three
      BH(4)-biosynthetic enzymes, we expressed Flag-fusion proteins in transiently
      transfected COS-1 cells and analyzed the distribution by immunolocalization and
      sub-cellular fractionation using anti-Flag antibodies and enzymatic assays.
      Whereas 5-10% of total GTPCH and PTPS and approximately 1% of total SR were
      present in the nucleus, only GTPCH was confirmed to be an active enzyme in
      nuclear fractions. The in vitro studies together with the tissue staining
      corroborate specific nuclear localization of BH(4)-biosynthetic proteins with yet
      unknown biological function.

PMID- 14729143
TI  - Role of the W07-toxin on Vibrio cholerae-induced diarrhoea.
AB  - Vibrio cholerae W07 strain isolated from a cholera epidemic in South India,
      lacked the ctx gene but could still secrete a novel toxin, the W07-toxin that
      could cause fluid accumulation in ligated rabbit ileal loop. The important
      intracellular messengers implicated in this study were Ca(2+), cyclic AMP,
      inositol triphosphate and protein kinase C (PKC). A number of inhibitors/channel
      blockers have further shown the major role of [Ca(2+)](i) in modulation of the
      toxin-induced cellular response. An increase in the level of reactive oxygen
      species (ROS) in the W07-toxin-stimulated enterocytes correlated with the
      decrease in the levels of antioxidant enzymes, catalase and superoxide dismutase
      (SOD). The reactive nitrogen intermediates (RNI) detected by measuring the levels
      of nitrite and citrulline, were found to be high in the enterocytes triggered
      with the W07-toxin, thereby indicating their role in toxin-mediated change in
      mucosal permeability. The precise role of the toxin has also been authenticated
      by conducting the experiments with W07-toxin preincubated in the presence of
      IgG(WT) (IgG isolated from antitoxin sera) or GM(1). Thus, a significant increase
      in the levels of second messengers and a decrease in antioxidant defenses appear
      to be important in mediating the fluid secretion caused by this novel toxin from
      V. cholerae W07.

PMID- 14729144
TI  - Genetic instability in EBV-transformed lymphoblastoid cell lines.
AB  - Epstein Barr virus (EBV)-transformed lymphoblastoid cell lines are commonly used
      to provide an inexhaustible supply of DNA. We examined microsatellite instability
      in these cell lines in 35 individuals where DNA was available from the original
      blood samples and from cultured cell lines. Mutations were observed in 0.3% of
      the analyses, thus providing a quantitative measure of somatic mutation rate.

PMID- 14729145
TI  - Molecular cloning and expression analysis of novel wheat cysteine protease.
AB  - A cDNA clone encoding a novel papain-like cysteine protease was isolated from
      wheat germ (Triticum aestivum). This cDNA encoded a 371-residue protein,
      designated WCP2, composed of signal peptide followed by a propeptide and a mature
      protease containing active site residues that are highly conserved among the
      papain family. The mature WCP2 protein (26 kDa) was detected in the quiescent
      embryo and its level of expression in the germinating embryo was greatly
      increased.

PMID- 14729146
TI  - Epithelial Anion Transport--An Integrative Perspective. Proceedings of a
      symposium. Southampton, United Kingdom, 31 March-4 April 2003.

PMID- 14729147
TI  - Rapid regulation of NaCl secretion by estuarine teleost fish: coping strategies
      for short-duration freshwater exposures.
AB  - This review summarizes the mechanism of Cl(-) active secretion and its regulation
      in estuarine teleost fish. Small estuarine fish such as the killifish, Fundulus
      heteroclitus, forage in shallow water following advancing tides and are exposed
      regularly to very dilute microenvironments. Using the killifish opercular
      epithelium and related teleost membranes containing mitochondria-rich cells, the
      regulation includes a reduction of active Cl(-) secretion and passive diffusive
      ion loss in a three-stage process spanning approximately 30 min. There is a
      combination of sympathetic neural reflex mediated by alpha(2)-adrenoceptors
      operating via intracellular inositol tris phosphate and intracellular Ca(2+) and
      a cellular hypotonic shock response, followed by covering over of ion-secreting
      cells by pavement cells. This effectively minimizes salt loss in dilute media.
      The upregulation of salt secretion on return to full strength seawater may be via
      hormones (arginine vasotocin and urotensin I) and neurotransmitter (vasoactive
      intestinal polypeptide) in combination with hypertonic shock. A hypothetical
      model includes involvement of protein kinase A and C and protein phosphatases 1
      and 2A in regulation of the NKCC1 cotransporter on the basolateral side and
      protein kinase A regulation of the CFTR-like apical anion channel.

PMID- 14729148
TI  - Na+ versus Cl- transport in the intact killifish after rapid salinity transfer.
AB  - Much of the early research elucidating the general mechanisms of euryhalinity was
      performed on the common killifish. More recently, its opercular epithelium with
      abundant mitochondria-rich cells has proven to be a powerful model for analyzing
      the mechanisms of active NaCl transport under Ussing conditions in vitro (i.e.,
      with isotonic saline on both surfaces, at short-circuit). However, it is unclear
      whether this preparation duplicates the gill under real world conditions-i.e., at
      open-circuit, with real seawater (SW) or freshwater (FW) on the mucosal surface.
      There have been only limited studies, mostly about 35 years ago, on ion transport
      in the intact killifish. Therefore, using radioisotopes (22Na, 36Cl), we
      developed and evaluated methods for the independent measurement of unidirectional
      Na(+) and Cl(-) influx and efflux rates and internal pools in intact killifish
      acclimated to 10% SW and abruptly transferred to either 100% SW or FW. Internal
      Na(+) pools were disturbed less than internal Cl(-) pools by transfer, and were
      corrected after 3 days in 100% SW or 7 days in FW. Influx and efflux rates in 10%
      SW were about 3000 micromol kg(-1) h(-1) and increased to 15,000-18,000 micromol
      kg(-1) h(-1) after transfer to 100% SW, remaining approximately equal and
      equimolar for Na(+) and Cl(-), and stable from 0.5 to 7 days post-transfer. After
      transfer to FW, Na(+) influx and efflux rates dropped to 1000-1500 micromol kg(
      1) h(-1), with efflux slightly exceeding influx, and remained approximately
      stable from 0.5 to 7 days. However, while Cl(-) efflux responded similarly, Cl(-)
      influx rate dropped immediately to negligible values (20-50 micromol kg(-1) h(
      1)) without recovery through 7 days. These results differ from early ion
      transport data in 100% SW, and demonstrate that fluxes stabilize quickly after
      salinity transfer. They also show that the intact animal responds more quickly
      than the epithelium, provide qualitative but not quantitative support for the
      opercular epithelium as a model for the gill under real world SW conditions, and
      no support for its use as a gill model under real world FW conditions, where
      branchial Cl(-) uptake is negligible.

PMID- 14729149
TI  - Proton pump-driven cutaneous chloride uptake in anuran amphibia.
AB  - Krogh introduced the concept of active ion uptake across surface epithelia of
      freshwater animals, and proved independent transports of Na(+) and Cl(-) in
      anuran skin and fish gill. He suggested that the fluxes of Na(+) and Cl(-)
      involve exchanges with ions of similar charge. In the so-called Krogh model, Cl(
      )/HCO(3)(-) and Na(+)/H(+) antiporters are located in the apical membrane of the
      osmoregulatory epithelium. More recent studies have shown that H(+) excretion in
      anuran skin is due to a V-ATPase in mitochondria-rich (MR) cells. The pump has
      been localized by immunostaining and H(+) fluxes estimated by pH-stat titration
      and mathematical modelling of pH-profiles in the unstirred layer on the external
      side of the epithelium. H(+) secretion is voltage-dependent, sensitive to
      carbonic-anhydrase inhibitors, and rheogenic with a charge/ion-flux ratio of
      unity. Cl(-) uptake from freshwater is saturating, voltage independent, and
      sensitive to DIDS and carbonic-anhydrase inhibitors. Depending on anuran species
      and probably on acid/base balance of the animal, apical exit of protons is
      coupled to an exchange of Cl(-) with base (HCO(3)(-)) either in the apical
      membrane (gamma-type of MR cell) or in the basolateral membrane (alpha-type MR
      cell). The gamma-cell model accounts for the rheogenic active uptake of Cl(-)
      observed in several anuran species. There is indirect evidence also for non
      rheogenic active uptake accomplished by a beta-type MR cell with apical base
      secretion and basolateral proton pumping. Several studies have indicated that the
      transport modes of MR cells are regulated via ion- and acid/base balance of the
      animal, but the signalling mechanisms have not been investigated. Estimates of
      energy consumption by the H(+)-ATPase and the Na(+)/K(+)-ATPase indicate that the
      gamma-cell accomplishes uptake of NaCl in normal and diluted freshwater. Under
      common freshwater conditions with serosa-positive or zero V(t), the K(+)
      conductance of the basolateral membrane would have to maintain the inward driving
      force for Na(+) uptake across the apical membrane. With the K(+) equilibrium
      potential across the basolateral membrane estimated to -105 mV, this would apply
      to external Na(+) concentrations down to 40-120 micromol/l. NaCl uptake from
      concentrations down to 10 micromol/l, as observed by Krogh, presupposes that the
      H(+) pump hyperpolarizes the apical membrane, which would then have to be
      associated with serosa-negative V(t). In diluted freshwater, exchange of cellular
      HCO(3)(-) with external Cl(-) seems to be possible only if the proton pump has
      the additional function of keeping the external concentration of HCO(3)(-) low.
      Quantitative considerations also lead to the conclusion that with the above
      extreme demand, at physiological intracellular pH of 7.2, the influx of Cl(-) via
      the apical antiporter and the passive exit of Cl(-) via basolateral channels
      would be possible within a common range of intracellular Cl(-) concentrations.

PMID- 14729150
TI  - Existence and nature of the chloride pump.
AB  - Seven widely documented mechanisms of chloride transport across plasma membranes
      are: anion-coupled antiport, sodium symport, sodium-potassium-chloride symport,
      potassium chloride symport, proton-coupled symport, an electrochemical coupling
      process and chloride channels. No direct genetic evidence has yet been provided
      for primary active chloride transport despite numerous reports of cellular Cl(-)-
      stimulated ATPases coexisting, in the same tissue, with uphill chloride transport
      that could not be accounted for by the four common chloride transport processes.
      Cl(-)-stimulated ATPases are a common property of practically all biological
      cells with the major location being of mitochondrial origin. It also appears that
      plasma membranes are sites of Cl(-)-stimulated ATPase activity. Recent studies of
      Cl(-)-stimulated ATPase activity and chloride transport in the same membrane
      system, including liposomes, suggest a mediation by the ATPase in net movement of
      chloride up its electrochemical gradient across plasma membranes. Further
      studies, especially from a molecular biological perspective, are required to
      confirm a direct transport role to plasma membrane-localized Cl(-)-stimulated
      ATPases.

PMID- 14729151
TI  - Beta-adrenergic receptors couple to CFTR chloride channels of intercalated
      mitochondria-rich cells in the heterocellular toad skin epithelium.
AB  - In the heterocellular toad skin epithelium the beta-adrenergic receptor agonist
      isoproterenol activates cyclic AMP-dependent Cl(-) channels that are not located
      in the principal cells. With four experimental approaches, in the present study,
      we tested the hypothesis that the signalling pathway targets apical CFTR-chloride
      channels of mitochondria-rich cells. (i) Serosal application of isoproterenol
      (log(10)EC50=-7.1+/0.2; Hill coefficient=1.1+/0.2), as well as nor-adrenaline,
      activated an anion pathway with an apical selectivity sequence, G(Cl)>G(Br)> or
      =G(NO(3))>G(I), comparable to the published selectivity sequence of cloned human
      CFTR expressed in Xenopus oocytes. (ii) Known modulators of human CFTR,
      glibenclamide (200 micromol/l) and genistein (50 micromol/l), depressed and
      activated, respectively, the receptor-stimulated G(Cl). Genistein did not modify
      the anion selectivity. (iii) Transcellular voltage clamp studies of single
      isolated mitochondria-rich cells revealed functional beta-adrenergic receptors on
      the basolateral membrane. With approximately 60,000 mitochondria-rich cells per
      cm(2), the saturating activation of 11.9+/-1.6 ns/cell accounted for the measured
      isoproterenol-activated transepithelial conductance of 600-900 micros/cm(2). In
      forskolin-stimulated cells, glibenclamide (200 micromol/l) reversibly inhibited
      the transcellular conductance by 9.6+/1.6 ns/cell. (iv) A nucleotide sequence of
      one third of the Bufo bufo CFTR gene corresponding to the R-domain and part of
      the first nucleotide binding domain (NBD1) including its Walker motif was
      amplified from gallbladder epithelium. Somewhat smaller sequences of the BbCFTR
      were cloned from lung and isolated skin epithelium. The above new results taken
      together with our previously identified small-conductance CFTR-like Cl(-) channel
      in the apical membrane of isolated mitochondria-rich cells provide compelling
      evidence that the toad's CFTR gene codes for a functional Cl(-) channel in the
      apical plasma membrane of this minority cell type.

PMID- 14729152
TI  - Cell volume regulation and swelling-activated chloride channels.
AB  - Maintenance of a constant volume is essential for normal cell function. Following
      cell swelling, as a consequence of reduction of extracellular osmolarity or
      increase of intracellular content of osmolytes, animal cells are able to restore
      their original volume by activation of potassium and chloride conductances. The
      loss of these ions, followed passively by water, is responsible for the
      homeostatic response called regulatory volume decrease (RVD). Activation of a
      chloride conductance upon cell swelling is a key step in RVD. Several proteins
      have been proposed as candidates for this chloride conductance. The status of the
      field is reviewed, with particular emphasis on ClC-3, a member of the ClC family
      which has been recently proposed as the chloride channel involved in cell volume
      regulation.

PMID- 14729153
TI  - Intestinal bicarbonate secretion in marine teleost fish-source of bicarbonate, pH
      sensitivity, and consequences for whole animal acid-base and calcium homeostasis.
AB  - Whole animal studies using seawater European flounder (Platichthys flesus)
      revealed that increasing intestinal [Ca(2+)] to 20 mM stimulated net HCO(3)(-)
      base secretion by 57%, but this was effectively balanced by an increase in net
      acid secretion, likely from the gills, to maintain whole animal acid-base status.
      Higher Ca(2+) concentrations (40 and 70 mM) in ambient seawater resulted in
      reduced plasma total CO(2). This indicates (1) imperfect acid-base compensation,
      and (2) that endogenous metabolic CO(2) is insufficient to fuel intestinal
      HCO(3)(-) secretion, under hyper-stimulated conditions. Bicarbonate secretion
      plays an important role in preventing calcium absorption by precipitating a large
      fraction of the imbibed calcium as CaCO(3). Indeed, under high Ca(2+) conditions
      (20 mM), up to 75% of the intestinal Ca(2+) is precipitated as CaCO(3) and then
      excreted. This is undoubtedly important in protecting the marine teleost kidney
      from the need for excessive calcium excretion and risk of renal stone formation.
      Using an in vitro pH-stat technique with the isolated intestinal epithelium, the
      replacement of serosal CO(2) with a HEPES buffered saline had no effect on
      HCO(3)(-) secretion, indicating that the endogenous supply of HCO(3)(-) from
      CO(2) hydration within epithelial cells is adequate for driving baseline
      secretion rates. Further, in vitro data demonstrated a stimulatory effect of low
      pH on intestinal HCO(3)(-) secretion. Thus, both luminal Ca(2+) and H(+) can
      regulate HCO(3)(-) secretion but the precise mechanisms and their potential
      interaction are currently unresolved.

PMID- 14729154
TI  - Integrated responses of Na+/HCO3- cotransporters and V-type H+-ATPases in the
      fish gill and kidney during respiratory acidosis.
AB  - Using degenerate primers, followed by 3' and 5' RACE and "long" PCR, a continuous
      4050-bp cDNA was obtained and sequenced from rainbow trout (Oncorhynchus mykiss)
      gill. The cDNA included an open reading frame encoding a deduced protein of 1088
      amino acids. A BLAST search of the GenBank protein database demonstrated that the
      trout gene shared high sequence similarity with several vertebrate Na(+)/HCO(3)(
      ) cotransporters (NBCs) and in particular, NBC1. Protein alignment revealed that
      the trout NBC is >80% identical to vertebrate NBC1s and phylogenetic analysis
      provided additional evidence that the trout NBC is indeed a homolog of NBC1.
      Using the same degenerate primers, a partial cDNA (404 bp) for NBC was obtained
      from eel (Anguilla rostrata) kidney. Analysis of the tissue distribution of trout
      NBC, as determined by Northern blot analysis and real-time PCR, indicated high
      transcript levels in several absorptive/secretory epithelia including gill,
      kidney and intestine and significant levels in liver. NBC mRNA was undetectable
      in eel gill by real-time PCR. In trout, the levels of gill NBC1 mRNA were
      increased markedly during respiratory acidosis induced by exposure to
      hypercarbia; this response was accompanied by a transient increase in branchial V
      type H(+)-ATPase mRNA levels. Assuming that the branchial NBC1 is localised to
      basolateral membranes of gill cells and operates in the influx mode (HCO(3)(-)
      and Na(+) entry into the cell), it would appear that in trout, the expression of
      branchial NBC1 is transcriptionally regulated to match the requirements of gill
      pHi regulation rather than to match trans-epithelial HCO(3)(-) efflux
      requirements for systemic acid-base balance. By analogy with mammalian systems,
      NBC1 in the kidney probably plays a role in the tubular reabsorption of both
      Na(+) and HCO(3)(-). During periods of respiratory acidosis, levels of renal NBC1
      mRNA increased (after a transient reduction) in both trout and eel, presumably to
      increase HCO(3)(-) reabsorption. This strategy, when coupled with increased
      urinary acidification associated with increased vacuolar H(+)-ATPase activity,
      ensures that HCO(3)(-) levels accumulate in the body fluids to restore pH.

PMID- 14729155
TI  - The molecular and cellular physiology of basolateral organic anion transport in
      mammalian renal tubules.
AB  - Basolateral transport of organic anions (OAs) into mammalian renal proximal
      tubule cells is a tertiary active transport process. The final step in this
      process involves movement of OA into the cells against its electrochemical
      gradient in exchange for alpha-ketoglutarate (alphaKG) moving down its
      electrochemical gradient. Two homologous transport proteins (OAT1 and OAT3) that
      function as basolateral OA/alphaKG exchangers have been cloned and sequenced. We
      are in the process of determining the functional distribution and regulation of
      OAT1 and OAT3 in renal tubules. We are using rabbit OAT1 (rbOAT1) and OAT3
      (rbOAT3) expressed in heterologous cell systems to determine substrate
      specificity and putative regulatory steps and isolated rabbit proximal renal
      tubule segments to determine functional distribution and physiological regulation
      of these transporters within their native epithelium. Rabbit OAT1 and OAT3 differ
      distinctly in substrate specificity. For example, rbOAT1 has a high affinity for
      the classical renal OA transport substrate, p-aminohippurate (PAH), whereas
      rbOAT3 has no affinity for PAH. In contrast, rbOAT3 has a high affinity for
      estrone sulfate (ES), whereas rbOAT1 has only a very slight affinity for ES. Both
      rbOAT1 and rbOAT3 appear to have about the same affinity for fluorescein (FL).
      These differences and similarities in substrate affinities make it possible to
      functionally map transporters along the renal tubules. Initial data indicate that
      OAT1 predominates in S2 segments of the rabbit proximal tubules, but studies of
      other segments are just beginning. Transport of a given substrate in any tubule
      segment depends on both the affinity of each transporter which can accept that
      substrate as well as the level of expression of each of those processes in that
      particular tubule segment. Basolateral PAH transport (presumably OAT1 activity)
      appears to be down-regulated by activation of protein kinase C (PKC) and up
      regulated via mitogen-activated protein kinase (MAPK) through phospholipase A(2)
      (PLA(2)), prostaglandin E(2) (PGE(2)), cyclic AMP, and protein kinase A (PKA)
      activation.

PMID- 14729156
TI  - Inorganic and organic anion transport by insect renal epithelia.
AB  - Insect renal organs typically exhibit high rates of transport of inorganic and
      organic anions, and therefore provide useful models for the study of epithelial
      anion transport and its control. Isolated Malpighian tubules of some species
      secrete a volume of iso-osmotic fluid equal to their own volume in 10-15 s, which
      means that cellular Cl(-) content is exchanged every 3-5 s. Anion transport can
      also be achieved against extreme thermodynamic gradients. The concentration of
      K(+) and Cl(-) in the lumen of the Malpighian tubules of some desert beetles
      approaches or exceeds saturation. A basolateral Na(+):K(+):2Cl(-) cotransporter
      plays an important role in vectorial ion transport in Malpighian tubules of many
      species, but there is also evidence for coupling of Cl(-) transport to the
      movement of a single cationic species (Na(+) or K(+)). Although an apical
      vacuolar H(+)-ATPase plays a primary role in energizing transepithelial secretion
      of chloride via channels or cotransporters in the secretory segment of the
      Malpighian tubule, several different ATPases have been implicated in reabsorption
      of Cl(-) by the lower Malpighian tubule or hindgut. Chloride transport is known
      to be controlled by several neuropeptides, amines and intracellular second
      messengers. Insect renal epithelia are also important in excretion of potentially
      toxic organic anions, and the transporters involved may play a role in resistance
      to insecticides of natural or anthropogenic origin.

PMID- 14729157
TI  - Sodium and chloride transport in soft water and hard water acclimated zebrafish
      (Danio rerio).
AB  - While the zebrafish is commonly used for studies of developmental biology and
      toxicology, very little is known about their osmoregulatory physiology. The
      present investigation of Na(+) and Cl(-) transport revealed that the zebrafish is
      able to tolerate extremely low ambient ion concentrations and that this is
      achieved at least in part by a greatly enhanced apparent uptake capacity and
      affinity for both ions. Zebrafish maintain plasma and whole body electrolyte
      concentrations similar to most other freshwater teleosts even in deionized water
      containing only 35 microM NaCl, i.e soft water. We recorded an extremely low
      transport affinity constant (K(m)) of 8+/-1 microM for the active uptake of Cl(-)
      in soft water acclimated fish, while other transport kinetic parameters were in
      agreement with reports for other freshwater organisms. While both Na(+) and Cl(-)
      uptake in soft water clearly depends on apical proton pump activity, changes in
      abundance and possibly localization of this protein did not appear to contribute
      to soft water acclimation. Active Cl(-) uptake was strongly dependent on
      branchial carbonic anhydrase (CA) activity regardless of water type, while the
      response of Na(+) transport to a CA inhibitor was more variable. Differential
      response of Na(+) uptake to amiloride depending on acclimation medium suggests
      that different Na(+) transport mechanisms are employed by zebrafish acclimated to
      soft and hard water.

PMID- 14729158
TI  - Relative importance of birth size and postnatal growth for women's educational
      achievement.
AB  - BACKGROUND: Child undernutrition, commonly measured by growth failure, is
      associated with functional disadvantages later in life. AIMS: To assess
      relationships between child growth and women's educational achievement (EA).
      STUDY DESIGN AND SUBJECTS: Women from four ladino Guatemalan villages were
      measured as children (1969-1977) and again at ages 20-29 years (1996-1999). The
      anthropometric measurements analyzed were weight, length, and head circumference
      (HC) at birth and 2 years and height at adulthood. Sample sizes were 120 at
      birth, 133 at 2 years, and 145 at adulthood; 108 cases had data at all three
      points. OUTCOME MEASURES: Women's EA was computed based on five educational tests
      and was categorized into quintiles. Analysis was based on a proportional odds
      model. Generalized estimating equations were used to account for sibling
      clustering. Multiple Stage Least Squares analyses were used to assess the
      relative importance of birth size and of early (birth to age 2 years) and late
      postnatal growth (2 years to adulthood). RESULTS: Size at 2 years (HC and length)
      but no indicator at birth was positively associated with women's EA. Schooling
      was a strong, positive predictor of women's EA (odds ratio (OR)=13.7, 95%
      confidence interval (CI) [6.1, 30.6]). Early postnatal growth but not birth size
      or late postnatal growth was associated with women's EA (OR with 1 standard
      deviation (S.D.) increment in length=1.5, 95% CI [1.05, 2.2]). CONCLUSIONS:
      Growth in length and HC from birth to 2 years of age, but not birth size or
      growth after 2 years, is an important predictor of women's EA.

PMID- 14729159
TI  - Perinatal changes of brain-derived neurotrophic factor in pre- and fullterm
      neonates.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is abundant in brain and
      peripheral nerves, affects normal development, growth and survival and is
      implicated in immune response. AIM: To determine in single preterm (P) and
      fullterm (F) neonates, circulating intra- and extrauterine levels of BDNF,
      supposingly reflecting their neuronal and immune maturity. STUDY DESIGN:
      Prospective study. SUBJECTS: Thirty healthy, appropriate for gestational age
      (AGA) F (mean gestational age 39.2+/-1.4 weeks), 15 healthy AGA P (29.4+/-1.3
      weeks), and their mothers. OUTCOME MEASURES: BDNF was measured by enzyme
      immunoassay methods in the serum of: mothers at the first stage of labor (MS),
      the umbilical cord (UC) and the neonates on days 1 (N1) and 4 (N4) postpartum.
      RESULTS: Levels of BDNF in (a). FMS did not differ from PMS, but both were
      significantly higher than respective (F or P) UC, N1 and N4 (p ranging from <0.01
      to <0.001), (b). FUC, FN1 and FN4 were significantly higher than PUC (p<0.001),
      PN1 (p<0.03) and PN4 (p<0.02), respectively, (c). PN1 increased significantly as
      compared to PUC (p<0.05). CONCLUSIONS: Higher BDNF MS levels may reflect the
      mature nervous and immune systems of mothers. Higher BDNF levels in F than P may
      also be due to advanced maturity in the former. Increased BDNF levels in PN1 as
      compared to PUC may indicate stimulation of immune response with exposure to
      antigenic stimuli from the extrauterine environment. Nevertheless, this
      stimulation is insufficient in P, who by decreasing N4 levels are by far less
      protected than F.

PMID- 14729160
TI  - Long-term oral sensitivity and feeding skills of low-risk pre-term infants.
AB  - This study examined the oral sensitivity and feeding skills of low-risk pre-term
      infants at 11-17 months corrected age. Twenty pre-term infants (PT) born between
      32 and 37 weeks at birth without any medical comorbidities were assessed. All of
      this PT group received supplemental nasogastric (NG) tube feeds during their
      birth-stay in hospital. A matched control group of 10 healthy full-term infants
      (FT) was also assessed. Oral sensitivity and feeding skills were assessed during
      a typical mealtime using the Royal Children's Hospital Oral Sensitivity Checklist
      (OSC) and the Pre-Speech Assessment Scale (PSAS). Results demonstrated that, at
      11-17 months corrected age, the PT group displayed significantly more behaviours
      suggestive of altered oral sensitivity and facial defensiveness, and a trend of
      more delayed feeding development than the FT group. Further, results demonstrated
      that, relative to the FT group, pre-term infants who received greater than 3
      weeks of NG feeding (PT>3NG) displayed significantly more facial defensive
      behaviour, and displayed significant delays across more aspects of their feeding
      development than pre-term infants who received less than 2 weeks of NG feeding
      (PT<2NG). The information from this preliminary study suggests that low-risk pre
      term infants, particularly those who receive supplemental NG feeding for greater
      than 3 weeks, may be at risk for displaying long-term altered oral sensitivity
      and facial defensiveness, as well as feeding delays. These observations warrant
      further investigation on this topic.

PMID- 14729161
TI  - Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal
      outcome and 2-year developmental outcome.
AB  - BACKGROUND AND OBJECTIVE: In the literature, there are conflicting data on the
      neonatal outcome in preterm infants who were delivered for maternal pre
      eclampsia. The purpose of this study is to investigate the effect of maternal pre
      eclampsia on neonatal morbidity and 2-year developmental outcome in a population
      of preterm infants delivered before 32 weeks of gestation. METHODS: The hospital
      records of all 89 surviving VLBW infants with GA below 32 weeks born from January
      1997 to December 1999 were reviewed retrospectively. Data on respiratory outcome,
      sepsis and intraventricular hemorrhage (IVH) were compiled and analyzed for their
      association to maternal pre-eclampsia. Seventy-eight infants were assessed
      employing the Bayley Scales of Infant Development for developmental outcome at 2
      years of corrected age. RESULTS: There was no difference in neonatal morbidity
      between groups. More infants born to pre-eclamptic mothers had lower MDI scores
      at 24 months of age (P=0.04) as compared to infants without maternal pre
      eclampsia. After multiple logistic regression analysis, pre-eclampsia (P=0.007,
      OR=10.8) remained a significant risk factor of mildly delayed MDI at 24 months of
      age. CONCLUSION: Delivery before 32 weeks because of pre-eclampsia was associated
      with an increased risk of poor cognitive outcome. There was no significant
      difference in the postnatal course in comparison with infants born after
      pregnancies not complicated by pre-eclampsia.

PMID- 14729162
TI  - Offspring sex and pregnancy outcome by length of gestation.
AB  - BACKGROUND: It takes a higher number of male than female embryos to produce a
      live born infant. The unbalanced pregnancy survival by offspring sex may also be
      reflected in higher proportion of preterm male births, and in unbalanced sex
      distribution in certain pregnancy conditions, such as preeclampsia. METHODS: We
      used data from the Medical Birth Registry of Norway, a population-based registry
      that has recorded births since 1967. For this study, we used information on
      offspring sex and length of gestation that was available for 1691053 (92.8%)
      singleton births among a total of 1822982 births from 1967 to 1998. We estimated
      sex ratios and perinatal mortality by length of gestation, and assessed whether
      the ratio of offspring sex in preeclampsia varied by length of gestation.
      RESULTS: For preterm births, there was a strong male dominance. Within five
      categories of gestational age between 16 and 36 weeks, the male/female ratios
      were 2.48, 1.26, 1.28, 1.32, and 1.28. At weeks 37-39, the sex ratio was 1.17,
      but at weeks 40-42 the number of male and female births was practically identical
      (sex ratio 1.00). Over all, the male/female ratio was 1.06. Perinatal mortality
      was consistently higher in males across the whole range of gestational age; in
      total it was 21% (95% CI, 18-25%) higher in male offspring. In preeclampsia with
      preterm delivery (<37 weeks), the sex ratio was reversed: female offspring was
      substantially more common than males (sex ratio 0.87), but in preeclampsia with
      delivery at term (37-42 weeks), the proportion of males was higher (sex ratio
      1.06) than for females. CONCLUSION: The sex differences by length of gestation
      and in preeclampsia may reflect that male embryos are subject to stronger
      intrauterine selection forces than females. Possibly, implantation may be the
      critical event, where offspring sex may be one of the factors that determine
      success.

PMID- 14729163
TI  - Does maternal blood cortisol entrain fetal diurnal rhythm?
AB  - AIMS: To evaluate whether maternal blood cortisol acts as an entrainer of the
      fetus, we compared diurnal variations in the fetal heart rate (FHR) of two cases
      with Cushing's syndrome, under condition of glucocorticoid replacement therapy
      after adrenalectomy. SUBJECTS: The Maternal cortisol concentration in Case 1
      showed bimodal change, at 31 and 38 weeks' gestation, while the concentration in
      Case 2 was found to have an abnormally high level with no diurnal variation at 30
      weeks and a monomodal pattern at 34 weeks. RESULTS: The FHR patterns in both
      cases demonstrated similar developmental change: a remarkable diurnal rhythm
      comparable to control cases was observed at 34-38 weeks. Analysis of spectral 1/f
      characteristics revealed, however, that Case 1 exhibited a pattern equivalent to
      control cases, whereas in Case 2, FHR values did not display overt diurnal
      variation. CONCLUSIONS: The diurnal rhythm of FHR develops irrespective of daily
      variation in maternal cortisol concentration.

PMID- 14729164
TI  - The effects of antenatal betamethasone administration on fetal heart rate and
      behaviour depend on gestational age.
AB  - OBJECTIVE: We previously reported decreases in fetal heart rate (FHR) variability
      and body and breathing movements after maternal betamethasone administration. We
      now test the hypothesis that fetal responsiveness to betamethasone depends on the
      gestational age at which glucocorticoid therapy is started. DESIGN OF THE STUDY:
      1-h recordings of FHR (n=350) and fetal movements (n=310) made during a 5-day
      period (days 0-4) were available for analysis. The recordings had been obtained
      from 63 pregnant women at high risk for preterm delivery who received
      betamethasone (two doses of 12 mg 24 h apart) between 26 and 34 weeks'
      gestational age (wGA). The response to betamethasone, i.e. the direction and
      magnitude of change in FHR and movement parameters compared with baseline (day
      0), was studied in relation to gestational age at drug administration. RESULTS:
      Fetuses exposed to betamethasone at 29-34 wGA showed a decrease in FHR on day 1
      (indicative of baroreceptor reflex), and reduced breathing activity and prolonged
      episodes of quiescence with a concomitant decrease in body movements on days 1
      and 2. However, these changes were not observed if betamethasone administration
      occurred at 26-28 wGA. Betamethasone-induced reductions in FHR variability were
      similar in young and older fetuses. CONCLUSIONS: Age-related differential
      responsiveness to betamethasone was found for all studied fetal processes (body
      and breathing movements, FHR, and quiescence), except FHR variability. Our
      results suggest ontogenic changes in the mechanisms presumed to underlie these
      processes (glucocorticoid receptor (GR) maturation, cardiovascular and neuro
      endocrine development).

PMID- 14729165
TI  - Serodiagnosis of Neospora caninum infection in cattle by enzyme-linked
      immunosorbent assay with recombinant truncated NcSAG1.
AB  - Neospora caninum is a veterinary medically important pathogen capable of causing
      abortion in cattle and neuromuscular paralysis in dogs. The surface antigen 1 of
      N. caninum (NcSAG1) is an important candidate for the development of a diagnostic
      reagent for neosporosis. In order to establish an effective diagnostic method,
      the gene encoding truncated NcSAG1 (NcSAG1t) lacking a signal peptide and C
      terminal hydrophobic regions was cloned and expressed in Escherichia coli as a
      fusion protein with glutathione S-transferase (GST). The purified GST-NcSAG1t was
      tested in an enzyme-linked immunosorbent assay (ELISA) for the detection of N.
      caninum antibodies in cattle. The ELISA with GST-NcSAG1t clearly differentiated
      between immunofluorescent antibody test (IFAT)-positive and -negative sera from
      cattle. In addition, the ELISA detected no cross-reactivity with sera from mice
      experimentally infected with the closely related parasite Toxoplasma gondii.
      Field serum samples collected from cattle in Brazil were examined for the
      diagnosis of neosporosis by using the ELISA. Of the 197 samples analyzed, 66
      (33.5%) samples were positive for antibodies to N. caninum. Of the 66 ELISA
      positive samples, 60 (90%) samples were confirmed as positive by Western blot
      analysis with whole parasite antigens. These results suggest that the recombinant
      NcSAG1t could be a reliable reagent for use as an antigen in ELISA for the
      serodiagnosis of N. caninum infection in cattle.

PMID- 14729166
TI  - Genotyping of Toxoplasma gondii isolates from chickens from India.
AB  - The present study was undertaken to isolate and genotype Toxoplasma gondii from
      free-range chickens (Gallus domesticus) from villages in Maharashtra and Tamil
      Nadu states of central and south India, respectively. Blood, heart, and brain
      from a total of 741 chickens were examined for T. gondii infection. Antibodies to
      T. gondii, as assayed with the modified agglutination test (MAT >or = 1:5) were
      found in 133 (17.9%) chickens. Hearts and brains of 186 chickens were bioassayed
      in mice. Additionally, hearts and/or brains of most of the seronegative (MAT <
      1:5) chickens were fed to 20 T. gondii-free cats, while 32 seropositive chickens
      (MAT 1:5) were fed to 3 cats. T. gondii was not isolated from any of the chickens
      by mouse bioassay. Five of the cats that were fed seronegative chickens shed
      oocysts, while isolates were not obtained from any of the other cats fed
      seropositive chickens. These five isolates, along with the two that were
      previously isolated in India through cat bioassay, were genetically analyzed.
      Genotyping using the SAG 2 locus indicated that two isolates were type II and
      five were type III. Microsatellite analysis revealed allelic differences between
      and within the lineages. This is the first report of genetic characterization of
      any T. gondii isolate from India.

PMID- 14729167
TI  - Aedes albopictus is a natural vector of Dirofilaria immitis in Italy.
AB  - Investigations were carried out in Padova town (Veneto region, NE Italy) to
      define the actual role of Aedes albopictus in the natural transmission of
      Dirofilaria nematodes, and to assess the risk that its presence might represent
      for veterinary and medical health. During summer 2000-2002 daytime captures of
      human-attracted mosquitoes were carried out in three areas of the town. The
      presence of filarial parasites in mosquitoes was evaluated by PCR, and sequencing
      confirmed species assessment. DNA extraction was performed separately on pools of
      the insect abdomen and thorax-head, to discriminate between Dirofilaria
      infected/infective specimens. A total of 2721 mosquitoes were caught and A.
      albopictus was the most abundant species (2534). Filarial DNA was found in 27.5%
      (19/69) of the abdomen pools formed with mosquitoes collected in summer 2000, and
      in 11.1% (16/144) and 4.9% (6/123) thorax-head pools coming from samplings 2001
      and 2002, respectively. Filarial DNA was belonging to D. immitis and all studied
      areas harboured infective specimens. These results prove A. albopictus as natural
      vector of D. immitis in Italy. Moreover, they support the hypothesis that the
      presence of the mosquito could affect the transmission pattern of canine
      heartworm disease in urban environment and, considering the aggressive
      anthropophylic behaviour of the species (30-48 bites/h) proven in Padova town,
      could enhance the circulation of filarial nematodes from animals to humans.

PMID- 14729168
TI  - Efficiency of feeding Duddingtonia flagrans chlamydospores to grazing ewes on
      reducing availability of parasitic nematode larvae on pasture.
AB  - Gastrointestinal nematodes are of concern in sheep production because of
      production and economic losses. Control of these nematodes is primarily based on
      the use of anthelmintic treatment and pasture management. The almost exclusive
      use of anthelmintic treatment has resulted in development of anthelmintic
      resistance which has led to the need for other parasite control options to be
      explored. The blood sucking abomasal parasitic nematode Haemonchus contortus
      causes severe losses in small ruminant production in the warm, humid sub-tropic
      and tropics. This study evaluated the effectiveness of a nematode trapping
      fungus, Duddingtonia flagrans, in reducing availability of parasitic nematode
      larvae, specifically H. contortus, on pasture. Chlamydospores of D. flagrans were
      mixed with a supplement feed which was fed daily to a group of crossbred ewes for
      the duration of the summer grazing season. A control group was fed the same
      supplement feed without chlamydospores. A reduction in infective larval numbers
      was observed in fecal cultures of the fungus-fed group. Herbage samples from the
      pasture grazed by the fungus-fed group also showed a reduction in infective
      larvae. There were no significant (P > 0.05) differences in overall fecal egg
      count, packed cell volume or animal weight between fungus-fed and control groups.
      Tracer animals were placed on the study pastures at the end of the study to
      assess pasture infectivity. Although tracer animals were only two per group,
      those that grazed with the fungus-fed group had substantially reduced (96.8%)
      nematode burdens as compared to those from the control group pasture. Results
      demonstrated that the fungus did have activity against nematode larvae in the
      feces which reduced pasture infectivity and subsequently nematode burdens in
      tracer animals. This study showed that D. flagrans, fed daily to grazing ewes,
      was an effective biological control agent in reducing a predominantly H.
      contortus larval population on pasture.

PMID- 14729169
TI  - Evaluation of anthelmintic properties of extracts from some plants used as
      livestock dewormers by pastoralist and smallholder farmers in Kenya against
      Heligmosomoides polygyrus infections in mice.
AB  - Parasitic nematodes are among the most common and economically important
      infectious diseases of grazing livestock, especially in small ruminants in the
      tropics and subtropics in Kenya the control of gastrointestinal nematode
      infections in sheep and goats is usually made with synthetic anthelmintics but
      substantial levels of anthelmintic resistance have been recorded. A number of
      medicinal plants, that may provide possible alternatives, and are used by
      pastoralists and smallholder farmers in Kenya as deworming agents for their
      livestock and equines, namely Aframomum sanguineum, Dodonea angustifolia,
      Hildebrandtia sepalosa, Myrsine africana, Rapanea melanophloeos from Kenya, and
      Azadirachta indica from Kenya and Malaysia, together with the chemicals embelin
      and santonin that occur in some of these plants, were evaluated against
      Heligmosomoides polygyrus in mice. Commercial anthelmintics, namely ivermectin,
      pyrantel and piperazine, were also investigated, both to validate the mouse model
      system and to assess efficacy of these drugs against H. polygyrus. Pyrantel and
      ivermectin were highly effective in reducing the numbers of H. polygyrus worms as
      well as eggs in faeces of the mice, but piperazine had a lower activity.
      Application of santonin and M. africana significantly reduced the number of total
      worm counts (TWC) but not faecal egg counts (FEC). The use of embelin, R.
      melanophloeos and A. indica reduced FEC but not TWC. In all cases, however,
      reductions were well below the a priori level of 70% required for biological
      significance. A. sanguineum, D. angustifolia and H. sepalosa had no effect on
      either TWC or FEC. In conclusion, none of the plant preparations had any
      biologically significant anthelmintic effect in this monogastric host-parasite
      model system.

PMID- 14729170
TI  - Efficacy of the nematode-trapping fungus Duddingtonia flagrans against three
      species of gastro-intestinal nematodes in laboratory faecal cultures from sheep
      and goats.
AB  - The ability of the nematode-killing fungus Duddingtonia flagrans to reduce number
      of infective larvae of three species of gastro-intestinal parasitic nematodes
      developing in dung was investigated in both goats and sheep. Groups of lambs and
      kids (12-20 weeks old) were given mono-specific infections of Haemonchus
      contortus, Ostertagia (Teladorsagia) circumcincta or Trichostrongylus
      colubriformis. Following patency of the infections (t1) faecal samples were
      collected for determination of faecal nematode egg count (FEC) and culture of
      parasite larvae. Groups of animals were then dosed on 2 consecutive days with one
      of the two dose rates of the fungus (250,000 or 500,000 spores/kg liveweight).
      One (t2) and 5 (t3) days after the second dose of fungus samples were again
      collected for FEC and culture. The number of larvae recovered from the faecal
      cultures at t1 and t3 were used as controls to assess the efficacy of the
      experimental treatment at t2. Average efficacy was 78% with group means ranging
      from 40 to 93%. Dose rate of fungus appeared to influence efficacy against O.
      circumcincta but not against H. contortus or T. colubriformis. Overall, there
      were no differences in the efficacy of the fungus against any of the parasite
      species or in either host animal. The results of this trial indicate the
      potential use of this fungus as a broad spectrum anti-parasite agent for use in
      both goats and sheep.

PMID- 14729171
TI  - Seasonal variations in the larval burden distribution of Oestrus ovis in sheep in
      the southwest of Spain.
AB  - A chronobiological study of oestrosis was conducted for larval instars of Oestrus
      ovis from November 2000 to September 2002 with the examination of 477 adult sheep
      of the southwest region of Spain. Skulls from slaughtered sheep were examined and
      the different O. ovis larval stages (L1, L2, L3) were recovered from the nasal
      sinus cavities. O. ovis larvae were detected in 339 sheep, reaching a prevalence
      of 71.1%. Only one farm was free of infested sheep indicating a prevalence of the
      97.91% among studied flocks. The mean larval burden was 18.54 larvae per infested
      head during the coldest months in the southwest of Spain when the larval burden
      reached its highest levels, especially of the first larval stage (L1). However,
      the maximum percentage of L1 coincided with the minimum percentage of the second
      larval stage (L2). The third larval stage (L3) was observed in relatively low
      levels during the entered study period, but two peaks occurred in April-May and
      in September-October. During the 2 years of sampling, all the different larval
      stages were simultaneously recovered throughout the year, indicating the
      existence of a long favourable period for the evolution and development of the
      larval instars, which would start between February and March and finishing in
      November.

PMID- 14729172
TI  - Hepatozoon spp.: report of some cases in dogs in Brasilia, Brazil.
AB  - Canine hepatozoonosis is a disease caused by the tick-borne protozoan Hepatozoon
      spp. It has been reported in the United States, southern Europe, the Middle East,
      Africa and the Far East. In Brazil, canine hepatozoonosis is an emerging
      protozoal tick-borne disease, and is characterized by distinct clinical signs.
      The objective of this study was to analyze the laboratory findings of some
      hepatozoonosis cases in dogs in Brasilia, Brazil, and their clinical signs. The
      animals of this experiment showed low parasitemia, similar to H. americanum, but
      the clinical signs presented were similar to H. canis. According to our
      observations and in agreement with O'Dwyer et al. [Vet. Parasitol. 94 (2001)
      143], the Brazilian Hepatozoon appears more to resemble the species found in the
      eastern Hemisphere than with H. americanum of North America, or could be caused
      by a new species. Our data revealed that hepatozoonosis could be considered
      endemic in Brasilia.

PMID- 14729173
TI  - The molecular mystery of neuronal migration: FAK and Cdk5.
AB  - The basic building blocks of a cell are its cytoskeletal proteins, the orderly
      but dynamic organization of which is essential. How signalling molecules regulate
      the cytoskeleton in the developing nervous system is still largely unknown. A
      recent breakthrough sheds light on a pathway involving Cdk5 (cyclin-dependent
      kinase 5) and FAK (focal adhesion kinase), demonstrating their role in regulating
      microtubule structure and thus nuclear positioning in radially migrating cortical
      neurones.

PMID- 14729174
TI  - Receptors and immune sensors: the complex entry path of human cytomegalovirus.
AB  - The ability of human cytomegalovirus (HCMV) to infect an extensive range of cell
      types has complicated efforts to identify cellular receptors for this significant
      pathogen. Recent findings demonstrate that epidermal growth factor receptor
      (EGFR) serves also as a receptor for HCMV. Additional evidence has shown that
      HCMV entry occurs in concert with immune detection through toll-like receptors.
      Here, the implications of EGFR activation, the existence of other receptors and
      the coordination of entry with the innate sensing are discussed.

PMID- 14729175
TI  - Bcl-w(edding) with mitochondria.
AB  - Bcl-2-family members (Bcl-2, Bax, Bcl-w and Bcl-x(L)) are crucial integrators of
      signals for cell survival and death; the pro- or antiapoptotic activities of
      these proteins are regulated by their subcellular localization. Bcl-2 directly
      inserts into the membranes, where it acts; however, Bax requires a stimulus
      dependent translocation from an inactive cytosolic to an active membrane-inserted
      state. Recently, a novel mechanism is described for the survival factor Bcl-w,
      which is active while weakly associated with mitochondria. In apoptotic cells, a
      BH3-only protein neutralizes the survival activity of Bcl-w by binding to its
      "hydrophobic pockets", thereby releasing its C-terminal domain and allowing its
      insertion into the membrane. Here, we discuss the importance of this finding for
      a better understanding of the action mode of Bcl-w and other Bcl-2-family
      members.

PMID- 14729176
TI  - Requirements for the identification of dense-core granules.
AB  - Dense-core granules (DCGs), cytoplasmic organelles competent for regulated
      exocytosis, show considerable heterogeneity depending upon the specificity of
      their expressing cells--primarily neurons and neurosecretory cells. DCGs have
      been mainly identified by detecting their cargo molecules, often members of the
      granin family, and using conventional electron microscopy and
      immunocytochemistry. However, by a critical analysis of the various stages of DCG
      "life" within neurosecretory cells, we have highlighted several specific
      molecular and functional properties that are common to all these organelles. We
      propose that these properties be considered as strict requirements for the
      identification of DCGs.

PMID- 14729177
TI  - A trip to the ER: coping with stress.
AB  - The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum
      (ER) induces a coordinated adaptive program called the unfolded protein response
      (UPR). The UPR alleviates stress by upregulating protein folding and degradation
      pathways in the ER and inhibiting protein synthesis. With a basic conceptual
      framework for the UPR, including the identification of key mediators of the
      response, now in place, recent work has turned towards investigating how the
      response is regulated and how its effects radiate beyond the immediate realm of
      protein secretion. This review highlights advances in these areas and attempts to
      forecast important issues that must be addressed soon.

PMID- 14729178
TI  - Enzyme activity--it's all about image.
AB  - Unraveling the functional roles of proteins is a major challenge facing the
      postgenome researcher. Advances towards this goal have been made through the
      development of both chemical and biochemical tools for monitoring protein
      activity. Recently, a myriad of fluorescence-based imaging tools have emerged for
      in vitro, in vivo and whole animal applications. These tools have provided
      methods to monitor the spatial and temporal distribution of proteins and
      bioorganic molecules dynamically. Here, recent advances in chemical and
      biochemical techniques that allow the detection of enzymatic activity within
      intact cells and in vivo are reviewed. Such technologies have the potential to be
      integrated into drug-development programs to facilitate both the functional
      validation of pharmaceutical targets and the treatment of human disease.

PMID- 14729179
TI  - How do Abl family kinases regulate cell shape and movement?
AB  - Genetic analysis and studies of normal and leukemia cells in culture have shown
      that Abl family nonreceptor tyrosine kinases regulate cell morphogenesis and
      motility. Abl family kinases, which include Drosophila (D-) Abl and the
      vertebrate Abl and Arg proteins, relay signals from cell surface growth-factor
      and adhesion receptors to promote cytoskeletal rearrangements. Recent biochemical
      and crystallographic analyses have clarified the mechanisms by which growth
      factor and adhesion receptors might regulate the activity of Abl family kinases.
      When activated, Abl family kinases can regulate cytoskeletal dynamics by
      phosphorylating several known cytoskeletal regulatory proteins. In addition, the
      C-terminal half of Abl family kinases has several domains that bind to
      cytoskeletal components. Emerging evidence suggests that Abl family kinases can
      use these domains to directly organize cytoskeletal structure in vivo.

PMID- 14729180
TI  - The ins and outs of Wingless signaling.
AB  - Signaling through the highly conserved Wingless/Wnt pathway plays a crucial role
      in a diverse array of developmental processes, many of which depend upon the
      precise regulation of Wingless/Wnt signaling levels. Recent evidence has
      indicated that the intracellular trafficking of Wingless/Wnt signaling components
      can result in significant changes in the level of signaling. Here, we examine
      three mechanisms through which intracellular trafficking might regulate Wingless
      signaling--the degradation of Wingless, its transport and the transduction of its
      signal. The intracellular trafficking of several Wingless/Wnt signaling
      components, including LRP5, LRP6, Dishevelled and Axin, as well as the functional
      implications of protein localization on Wingless/Wnt signaling, will be
      discussed.

PMID- 14729210
TI  - Illuminating the molecular basis of gene-for-gene resistance; Arabidopsis
      thaliana RRS1-R and its interaction with Ralstonia solanacearum popP2.
AB  - Elucidation of the molecular basis of gene-for-gene interactions between disease
      resistance (R) genes and pathogen avirulence (avr) genes has been a Holy Grail of
      plant pathology for the past decade. Recent studies of the R-avr interaction
      between RRS1-R and popP2 by Laurent Deslandes et al. provide new insights and
      suggest a direct physical association of the encoded proteins in support of a
      simplistic receptor-ligand model. However, careful consideration of the
      experimental findings reveals that they could also be explained by molecular
      linker proteins that mediate formation of a PopP2 and RRS1-R uniting complex.

PMID- 14729211
TI  - Race nonspecific resistance for potato late blight.
AB  - The late blight fungus (Phytophthora infestans) rots susceptible species of
      potato plants. None of the major varieties of potato (Solanum tuberosum) grown in
      the USA is resistant to US-8, the most prevalent genotype of the fungus. Now,
      Junqi Song, James Bradeen and colleagues have cloned the RB gene from the wild
      diploid potato species, Solanum bulbocastanum, using a map-based approach in
      combination with long-range PCR. Transgenic plants containing the gene, normally
      fully susceptible, displayed broad-spectrum late blight resistance.

PMID- 14729212
TI  - Vacuolar compartmentalization: a second-generation approach to engineering plants
      for phytoremediation.
AB  - Engineering plants with greater metal tolerance and accumulation properties is
      the key to developing phytoremediators. A recent study by Won-Yong Song et al.
      has shown that overexpressing the yeast vacuolar transporter YCF1 increases Pb
      and Cd tolerance and consequently increases the accumulation of these metals in
      shoots of transgenic Arabidopsis plants even though expression levels of YCF1
      were relatively low. This technology can be used to engineer advanced
      phytoremediators, increasing their ability to pump heavy metals into a safe
      compartment while requiring only a small amount of transporters rather than a
      large amount of chelating peptide material.

PMID- 14729213
TI  - Indian publishing: enduring the boom.
AB  - There has been a boom in the publication of Indian plant science research in
      recent years, defying national trends in other sciences and outperforming the
      international trends in plant science publications. This boom augurs well for
      India considering the importance of agriculture to her economy and the crucial
      need for science-based solutions to break the yield barriers. However, sustaining
      it requires tackling the problems of funding, infrastructure, manpower and other
      policy issues.

PMID- 14729214
TI  - POPP the question: what do LEA proteins do?
AB  - Late embryogenesis abundant (LEA) proteins are produced in maturing seeds and
      anhydrobiotic plants, animals and microorganisms, in which their expression
      correlates with desiccation tolerance. However, their function has remained
      obscure for 20 years. We argue that novel computational tools devised for non
      globular proteins might now overcome this problem. Predictions arising from
      bioinformatics fit well with recent data on Group 3 proteins, which potentially
      form cytoskeletal filaments, and suggest experimentally testable functions for
      these and other LEA protein groups.

PMID- 14729215
TI  - Evolution of oxygenic photosynthesis: genome-wide analysis of the OEC extrinsic
      proteins.
AB  - The appearance of oxygenic photosynthesis was a key event in the evolution of our
      green biosphere. Oxygen in the atmosphere is generally believed to come from the
      biomolecular water-splitting reaction that occurs in oxyphotosynthetic organisms
      catalysed by the oxygen evolving centre (OEC) of Photosystem II. Using knowledge
      from complete genomes and current databases, we have investigated the nature and
      composition of the extrinsic proteins forming the OECs of different organisms,
      with particular focus on the manganese stabilizing protein that is present in all
      known oxyphototrophs. This analysis traces the evolution of the extrinsic
      proteins from ancient cyanobacteria to higher plants and gives hints about the
      ancestral form of the OEC.

PMID- 14729216
TI  - How plants communicate using the underground information superhighway.
AB  - The rhizosphere is a densely populated area in which plant roots must compete
      with invading root systems of neighboring plants for space, water, and mineral
      nutrients, and with other soil-borne organisms, including bacteria and fungi.
      Root-root and root-microbe communications are continuous occurrences in this
      biologically active soil zone. How do roots manage to simultaneously communicate
      with neighboring plants, and with symbiotic and pathogenic organisms within this
      crowded rhizosphere? Increasing evidence suggests that root exudates might
      initiate and manipulate biological and physical interactions between roots and
      soil organisms, and thus play an active role in root-root and root-microbe
      communication.

PMID- 14729217
TI  - Getting the message across: how do plant cells exchange macromolecular complexes?
AB  - A major pathway for macromolecular exchange in plants involves plasmodesmata
      (PD), the small pores that connect adjoining cells. This article considers the
      nature of macromolecular complexes (MCs) that pass through PD and the pathways
      and mechanisms that guide them to the PD pore. Recent cell-biological studies
      have identified proteins involved in the directional trafficking of MCs to PD,
      and yeast two-hybrid studies have isolated novel host proteins that interact with
      viral movement proteins. Collectively, these studies are yielding important clues
      in the search for components that compose the plant intercellular MC trafficking
      pathway. Here, they are placed in the context of a functional model that links
      the cytoskeleton, chaperones and secretory pathway in the intercellular
      trafficking of MCs.

PMID- 14729218
TI  - From weeds to crops: genetic analysis of root development in cereals.
AB  - Root development of Arabidopsis, Zea mays (maize) and Oryza sativa (rice) differs
      in both overall architecture and the anatomy of individual roots. In maize and
      rice, the post-embryonic shoot-borne root system becomes the major backbone of
      the root stock; in Arabidopsis, the embryonic root system formed by a simple
      primary root and its lateral roots remains dominant. Recently, several specific
      root mutants and root-specific genes have been identified and characterized in
      maize and rice. Interestingly, some of these mutants indicate that the formation
      of primary-, seminal-, crown- and lateral roots is regulated by alternative root
      type-specific pathways. Further analyses of these unique pathways will contribute
      to the understanding of the complex molecular networks involved in cereal root
      formation.

PMID- 14729219
TI  - Poplar genome sequence: functional genomics in an ecologically dominant plant
      species.
AB  - In addition to their value for wood products, members of the genus Populus
      (poplars) provide a range of ecological services, including carbon sequestration,
      bioremediation, nutrient cycling, biofiltration and diverse habitats. They are
      also widely used model organisms for tree molecular biology and biotechnology.
      The sequencing of the poplar genome to an approximately 6x depth adds to a long
      list of important attributes for research. These include facile transformation,
      vegetative propagation, rapid growth, modest genome size and extensive expressed
      sequence tags. Here, we discuss how the genome sequence and transformability of
      poplar, together with its high levels of genetic and ecological diversity, are
      enabling new insights into the genetic programs controlling ontogeny, ecological
      adaptation and environmental physiology of trees.

PMID- 14729221
TI  - Role of the medial prefrontal cortex in N-methyl-D-aspartate receptor antagonist
      induced sensorimotor gating deficit in rats.
AB  - The medial prefrontal cortex (mPFC) regulates sensorimotor gating measured as
      prepulse inhibition (PPI) of startle. We here tested the effect of lesions of the
      mPFC on the PPI-disruptive effect of the non-competitive NMDA receptor antagonist
      dizocilpine in rats. Neurotoxic lesions of the mPFC were induced by ibotenic
      acid. Rats were tested for PPI after systemic injection of dizocilpine (0.15
      mg/kg) and after injection of the dopamine receptor agonist apomorphine (2
      mg/kg). Dizocilpine failed to disrupt PPI in rats with mPFC lesions while the PPI
      disruptive effect of apomorphine was not affected. Startle response magnitude in
      the absence of prepulses was not affected by mPFC lesions or drugs. These data
      suggest that the mPFC is an important brain region within the neuronal circuit
      responsible for NMDA receptor antagonist induced PPI-deficits.

PMID- 14729220
TI  - Attenuation of the effects of fluoxetine on serotonergic neuronal activity by
      pindolol in rats.
AB  - Based on its proposed ability to block the effect of selective serotonin reuptake
      inhibitors (SSRIs) on the firing rate of serotonergic neurons, the 5-HT1A partial
      agonist/beta-adrenergic antagonist pindolol has been examined in clinical trials
      for its ability to enhance the efficacy of SSRIs. However, varying results have
      been obtained in these clinical trials. To explore this issue, we examined the
      effects of pindolol alone and in combination with fluoxetine on the
      electrophysiological activity of serotonergic neurons in the dorsal raphe nucleus
      of anesthetized rats. Administration of pindolol (1, 5, and 20 mg/kg, s.c.) alone
      decreased the number of spontaneously active serotonergic neurons. Administration
      of fluoxetine (10 mg/kg, i.p.) alone also decreased the number of spontaneously
      active serotonergic neurons. However, when administered following fluoxetine,
      pindolol significantly attenuated, but did not block completely, the inhibitory
      effects of fluoxetine on the number of spontaneously active serotonergic neurons.
      These results indicate that pindolol can attenuate the effects of fluoxetine on
      the firing of serotonergic neurons. These results may help explain the varying
      efficacy of pindolol in clinical trials with SSRIs.

PMID- 14729222
TI  - Kinetics of [35S]dATPalphaS interaction with P2Y1 purinoceptor in rat brain
      membranes.
AB  - Kinetics of [35S]dATPalphaS (2'deoxyadenosine-5'-[alpha-35S]-thiotriphosphate)
      interaction with rat brain membrane fragments was studied at 25 degrees C and at
      radioligand concentrations from 2 to 250 nM. At least two different ways of
      [35S]dATPalphaS interaction with the membranes were distinguished on the basis of
      radioligand on-rate. Firstly, the binding sites characterized by 'fast' on-rate
      can be observed. Secondly, the 'slow' binding sites were kinetically identified
      and quantified. As in both cases the bound radioligand could be displaced by
      excess of ATP, all these binding sites can be defined as 'specific sites'. In the
      'slow' binding sites isomerization of the receptor-ligand complex was observed,
      as is typical for interaction of antagonists with G-protein coupled receptors,
      and the kinetic parameters for this interaction were similar with the appropriate
      data for the hP2Y1 receptors expressed in 1321N1 astrocytoma cells Therefore
      these sites could be assigned to the same receptor subtype in brain membranes
      while the 'fast' binding sites belong to other membrane-bound proteins, also
      interacting with ATP and its analogues. The kinetic properties of the latter
      sites were not analysed in detail.

PMID- 14729223
TI  - Synergistic interaction between mazindol, an anorectic drug, and swim-stress on
      analgesic responses in the formalin test in mice.
AB  - The present study examined the interaction between mazindol (MZ), an anorectic
      drug extensively used in Brazil and opioid/non-opioid endogenous analgesic
      systems activated by swim-stress. Further, the role of opioid, dopamine and N
      methyl-D-aspartate (NMDA) receptors in mediating the analgesic effect was
      evaluated. The stress-induced analgesia of a 3-min swimming at 32 degrees C
      (opioid/non-opioid) and 20 degrees C (non-opioid) were assessed using the
      formalin test. Male Swiss mice were intraperitoneally injected with naloxone (1.0
      mg/kg), sulpiride (3.0 mg/kg), MK-801 (0.075 mg/kg) or saline/vehicle 15 min
      prior, and with MZ (0.5 mg/kg) or saline/vehicle 5 min prior to swimming. The
      dose of MZ (0.5 mg/kg) did not cause analgesic effect, however, the association
      of MZ and swim-stress at both temperatures displayed synergistic interaction on
      analgesia that was blocked by sulpiride and MK-801 but not by naloxone. The
      present results suggest that MZ and swim-stress acted synergistically on
      analgesic responses, involving mainly the non-opioid component and possibly
      mediated by dopamine D2 receptors and NMDA receptors.

PMID- 14729224
TI  - Pattern of rapid-eye movement sleep episode occurrence after an immobilization
      stress in the rat.
AB  - Rapid-eye movement sleep (REMS) in the rat occurs in the form of episodes
      separated by long (>3 min: isolated REMS episodes, IREMSEs) and short (<3 min:
      sequential REMS episodes, SREMSEs) intervals. The mechanism clustering SREMSEs is
      thought to be better suited to increase the amount of REMS when its drive is
      high. We tested this hypothesis in a new situation by transiently augmenting this
      drive with a moderate psychogenic stress. After a 90-min immobilization stress,
      REMS increased by 54% over the rest of the dark phase. This increase was
      associated with a modest increase in IREMSEs (+40%), but a massive increase in
      SREMSEs (+300%). Thus, the mechanism that clusters REMS episodes operates in
      response to a moderate psychogenic stress imposed in standard laboratory
      conditions and not preceded by sleep deprivation.

PMID- 14729225
TI  - Adenosine administration produces an antidepressant-like effect in mice: evidence
      for the involvement of A1 and A2A receptors.
AB  - This study investigated the effect of adenosine in the forced swimming test (FST)
      and the tail suspension test (TST) in mice, and the contribution of adenosine A1
      and A2A receptors to adenosine's antidepressant-like effect. The immobility time
      in the FST was reduced by adenosine given either by i.p. (5-10 mg/kg) or i.c.v.
      (0.01-10 microg/site) route. Adenosine (1-10 mg/kg, i.p.) also produced an
      antidepressant-like effect in the TST. No treatment affected locomotion in an
      open-field. The anti-immobility effect of adenosine (10 mg/kg, i.p.) in the FST
      was prevented by i.p. pretreatment of mice with caffeine (3 mg/kg), DPCPX (2
      mg/kg) and ZM241385 (1 mg/kg). CHA (0.05 mg/kg, i.p.) and DPMA (1-5 mg/kg, i.p.)
      also produced an antidepressant-like effect in the FST. This is the first report
      of an antidepressant-like effect of adenosine in mice, apparently mediated
      through an interaction with A1 and A2A receptors.

PMID- 14729226
TI  - Functional connectivity patterns of human magnetoencephalographic recordings: a
      'small-world' network?
AB  - EEG and MEG (magnetoencephalography) are widely used to study functional
      connectivity between different brain regions. We address the question whether
      such connectivity patterns display an optimal organization for information
      processing. MEG recordings of five healthy human subjects were converted to
      sparsely connected graphs (N=126; k=15) by applying a suitable threshold to the N
      * N matrix of synchronization strengths. For intermediate frequencies (8-30 Hz)
      the synchronization patterns were similar to those of an ordered graph with a
      consistent drop of synchronization strength as a function of distance. For low
      (<8 Hz) and high (>30 Hz) frequency bands the synchronization patterns displayed
      the features of a so-called 'small-world' network. This might reflect an optimal
      organization pattern for information processing, connecting any two brain area by
      only a small number of intermediate steps.

PMID- 14729227
TI  - Identification and functional evidence of GABAergic neurons in parts of the brain
      of adult zebrafish (Danio rerio).
AB  - The distribution of GABA-containing neurons was studied in the brain of the adult
      zebrafish by Nissl staining and immunohistochemistry. GABA immunoreactivity (GABA
      IR) was demonstrated in parts of the brain such as olfactory bulb (OB),
      telencephalon, tectum stratum, and in the hypothalamus. GABA-IR appeared in the
      area where Nissl-stained cell bodies were abundant. The internal cellular layer
      of the OB was most densely stained by Nissl staining, and also showed a high
      level of GABA-IR. The telencephalon and the hypothalamus revealed a similar
      pattern to the OB in terms of Nissl staining and GABA-IR. However, the
      distribution and shape of stained cells of the tectum stratum were distinct from
      those in other regions: Nissl-stained neurons were ubiquitously present
      throughout all cellular layers including the stratum griseum centrale, the
      stratum album centrale (SAC), and the stratum periventriculare (SP). However,
      GABA-IR was weakly expressed in a limited number of neurons only in the SAC and
      SP. Whether GABA serves as an inhibitory neurotransmitter was also tested in the
      isolated telencephalon preparation by using extracellular field potential
      recordings. The synaptic activity recorded in the posterior dorsal telencephalon
      in response to the electrical stimulation of the anterior dorsal telencephalon
      was increased in the presence of the GABAA receptor antagonist, BMI, suggesting
      an inhibitory role for GABA-immunoreactive neurons in the adult brain of the
      zebrafish.

PMID- 14729228
TI  - Antipyretic effect of acetaminophen by inhibition of glutamate release after
      staphylococcal enterotoxin A fever in rabbits.
AB  - The present study was designed to determine whether the inhibition of glutamate
      release in organum vasculosum laminae terminalis (OVLT) of rabbit brain by
      acetaminophen might be protective in a whole-animal model of staphylococcal
      enterotoxin A (SEA) fever. Unanesthetized rabbits were administered intravenously
      with SEA, and both colonic temperature (Tco) and glutamate release in OVLT were
      measured simultaneously. The glutamate release in OVLT was measured with a
      microdialysis probe previously implanted. Both the Tco and glutamate release in
      OVLT were simultaneously increased following intravenous administration of SEA.
      The SEA-induced rise in both the Tco and the levels of glutamate release in OVLT
      were suppressed by pretreatment with intravenous injection of acetaminophen (1, 5
      or 10 mg/kg). Furthermore, treatment of OVLT with acetaminophen (50-150 microg)
      attenuated the fever-like hyperthermia induced by intra-OVLT injection of
      glutamate. Our results show acetaminophen may reduce glutamate release in OVLT
      and result in antipyresis.

PMID- 14729229
TI  - A single nucleotide polymorphism in glycogen synthase kinase 3-beta promoter gene
      influences onset of illness in patients affected by bipolar disorder.
AB  - Genetic studies in medicine exploited age of onset as a criterion to delineate
      subgroups of illness. Bipolar patients stratified with this criterion were shown
      to share clinical characteristics and patterns of inheritance of illness. The
      molecular mechanisms driving the biological clock in the suprachiasmatic nucleus
      of the hypothalamus may play a role in mood disorders. A single nucleotide
      polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171
      to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has
      been identified. GSK3-beta codes for an enzyme which is a target for the action
      of lithium and which is also known to regulate circadian rhythms in Drosophila.
      We studied the effect of this polymorphism on the age at onset of bipolar
      disorder type I. A homogeneous sample of 185 Italian patients affected by bipolar
      disorder was genotyped. Age at onset was retrospectively ascertained with best
      estimation procedures. No association was detected between GSK3-beta -50 T/C SNP
      and the presence of bipolar illness. Homozygotes for the wild variant (T/T)
      showed an earlier age at onset than carriers of the mutant allele (F=5.53,
      d.f.=2,182, P=0.0047). Results warrant interest for the variants of genes
      pertaining to the molecular clock as possible endophenotypes of bipolar disorder,
      but caution ought to be taken in interpreting these preliminary results and
      future replication studies must be awaited.

PMID- 14729230
TI  - Statins potentiate caspase-3 activity in immortalized murine neurons.
AB  - Statins are lipid-lowering drugs that have been shown to reduce atherosclerotic
      cardiovascular morbidity and mortality. However, there is growing evidence from
      epidemiological studies that long-term treatment with statins has unwanted
      effects on extrahepatic tissue and increases the risk for neuropathy. To
      investigate underlying molecular mechanisms we analyzed whether statins influence
      the activity of caspase-3 in immortalized neurons. Lovastatin and mevastatin are
      not able to activate caspase-3 but they strongly potentiate its activity when
      apoptotic signal transduction is initiated by staurosporine. The increase in
      caspase-3 activity after coincubation with statins and staurosporine was
      paralleled by an increase in the protein level of the pro-apoptotic GTPase RhoB.
      Our data provide evidence that statins enhance neuronal apoptosis and therefore
      give reasons for a careful evaluation when patients with neurological diseases
      are treated with these drugs.

PMID- 14729231
TI  - Differential expression of tetrodotoxin-resistant sodium channels Nav1.8 and
      Nav1.9 in normal and inflamed rats.
AB  - In an attempt to understand mechanisms underlying peripheral sensitization of
      primary afferent fibers, we investigated the presence of the tetrodotoxin
      resistant Na+ channel subunits Nav1.8 (SNS) and Nav1.9 (SNS2) on axons in digital
      nerves of normal and inflamed rat hindpaws. In normal animals, 14.3% of the
      unmyelinated and 10.7% of the myelinated axons labeled for the Nav1.8 subunit.
      These percentages significantly increased in 48 h inflamed animals to 22.0% (1.5
      fold increase) and 57.5% (6-fold increase) for unmyelinated and myelinated axons,
      respectively. In normal animals, Nav1.9 labeled 9.9% of the unmyelinated and 2.1%
      of the myelinated axons and following inflammation, the proportion of Nav1.9
      labeled unmyelinated axons significantly decreased to 3.0% with no change in the
      proportion of labeled myelinated axons. These data indicate that Nav1.8 and
      Nav1.9 subunits are transported to the periphery in normal animals and are
      differentially regulated during inflammation. The massive increase in Nav1.8
      expression in myelinated axons suggests that these may contribute to peripheral
      sensitization and inflammatory hyperalgesia.

PMID- 14729232
TI  - Deficits of non-verbal auditory perception in postlingually deaf humans using
      cochlear implants.
AB  - Temporal integration in the time domain of a few seconds was investigated with a
      subjective accentuation paradigm in 11 monochannel cochlear implant users, who
      showed auditory comprehension deficits. While listening to metronome beats
      generated at various frequencies, patients were asked to accentuate mentally
      every n-th beat and create an individual rhythmic pattern. The extent of temporal
      integration was defined as the duration of perceptual units consisting of
      subjectively grouped beats at particular metronome frequencies. The results
      indicate that there is reduced capacity for temporal integration in implant
      recipients, particularly for lower metronome frequencies, in comparison to
      normally hearing. These observations point to the coincidence of specific
      temporal processing disorders and deficits in auditory comprehension after
      cochlear implantation.

PMID- 14729233
TI  - Prevalence of serum antibodies to caudate nucleus in autistic children.
AB  - Autism may involve autoimmunity to brain. We studied regional distribution of
      antibodies to rat caudate nucleus, cerebral cortex, cerebellum, brain stem and
      hippocampus. The study included 30 normal and 68 autistic children. Antibodies
      were assayed by immunoblotting. Autistic children, but not normal children, had
      antibodies to caudate nucleus (49% positive sera), cerebral cortex (18% positive
      sera) and cerebellum (9% positive sera). Brain stem and hippocampus were
      negative. Antibodies to caudate nucleus were directed towards three proteins
      having 160, 115 and 49 kD molecular weights. Since a significant number of
      autistic children had antibodies to caudate nucleus, we propose that an
      autoimmune reaction to this brain region may cause neurological impairments in
      autistic children. Thus, the caudate nucleus might be involved in the
      neurobiology of autism.

PMID- 14729234
TI  - Polyamine levels in brain and plasma after acute restraint or water-immersion
      restraint stress in mice.
AB  - To investigate the relationship between polyamines and stress, we measured
      polyamine levels in the frontal cortex, hippocampus, hypothalamus, and plasma of
      mice after acute restraint or water-immersion restraint stress. In all parts of
      the brain, putrescine levels were elevated (139-157% of the control) 24 h after
      water-immersion restraint stress. In the case of restraint, however, elevation of
      the putrescine level (130% of the control) was detected only in the frontal
      cortex. Spermidine and spermine levels were unchanged or slightly reduced (80-85%
      of the control) in the brain 6 and 24 h after water-immersion restraint stress.
      There was no change in plasma polyamine levels at any time subsequent to the
      stress. Pretreatment with diazepam (5 mg/kg, i.p.) completely blocked the stress
      induced putrescine increases. These results indicate that the magnitude of the
      putrescine increase is dependent upon the intensity of the stressor, and suggest
      that polyamine metabolism is linked to psychological stress.

PMID- 14729235
TI  - Altered synaptic activities in cultures of neocortical neurons from prenatally X
      irradiated rats.
AB  - Prenatal X-irradiation can induce severe microcephaly in the brains of offspring.
      The possible alteration of neuronal synapse formation was examined in such X
      irradiated rats with microcephaly using the whole-cell current clamp technique.
      The total number of neocortical cells from prenatally (E16) X-irradiated rats
      decreased to 16% of the control value, while the ratio of GABA-positive/MAP2
      positive neurons increased 2.2-fold. Neocortical neurons from E17 normal rat
      fetuses cultured on monolayers of astrocytes for 7-10 days exhibited synchronized
      synaptically-driven rhythmic depolarizing potentials (RDPs). Neocortical neurons
      from prenatally (E15 or E16) X-irradiated rats also exhibited synchronized RDPs,
      however, their amplitude and the number of spikes decreased. These results
      suggest that, although neurons which survive in X-irradiated rats can form
      synapses, inhibitory inputs are predominant over excitatory inputs. It is
      possible that not only acute neuronal loss induced by X-irradiation but also
      increased inhibitory inputs in neocortex give rise to subsequent neurological
      disorders in X-irradiated rats.

PMID- 14729236
TI  - Changes in motor cortical excitability in humans following orally administered
      theophylline.
AB  - The effects of theophylline on human corticospinal excitability were studied
      using transcranial magnetic stimulation (TMS) before and after double-blind oral
      administration of theophylline or placebo in 20 healthy volunteers. TMS
      measurements included resting and active motor threshold, silent period,
      intracortical inhibition (ICI), and intracortical facilitation. F-wave and
      compound muscle action potential (CMAP) were also measured. Theophylline produces
      a reduction in ICI, while other parameters of corticospinal excitability remained
      unaffected. Since ICI is thought to depend on GABAA intracortical inhibitory
      mechanisms, our data suggest that the increase of human motor cortex excitability
      is the result of a decrease in GABAergic transmission. Our results further
      support the hypothesis that theophylline might induce convulsions by inhibiting
      GABAA receptor binding.

PMID- 14729237
TI  - Association study of the human partially duplicated alpha7 nicotinic
      acetylcholine receptor genetic variant with bipolar disorder.
AB  - The human alpha7 nicotinic acetylcholine receptor subunit (CHRNA7) gene cluster
      maps to the chromosome 15q13-q14 and is implicated as a candidate gene for
      bipolar disorder (BPD) by genetic linkage study. A -2 bp deletion polymorphism
      has been found in the duplicated CHRNA7 (CHRNA7-like) gene, which is located 1 Mb
      apart from CHRNA7. We tested the hypothesis that the allelic variant, 2 bp
      deletion (-2 bp), confers susceptibility to BPD or is related to the psychotic
      features of BPD. We genotyped the -2 bp polymorphism in 77 patients with BPD and
      135 normal controls. The distribution of -2 bp genotypes showed a moderately
      significant difference between the BPD patients and controls (P=0.044). Three BPD
      patients carried more than two alleles of the -2 bp deletion genotype, while this
      genotype was not found in the control group. The -2 bp polymorphism was not
      associated with age of onset or psychotic features in BPD patients. The results
      of this study suggest that the -2 bp polymorphism or a nearby polymorphism may
      play a role in the pathogenesis of BPD. Determination of the functional impact of
      the -2 bp variant in the nervous system and, in particular, the effect of
      harboring more than two alleles of the -2 bp deletion needs further exploration.

PMID- 14729238
TI  - Inhibitory actions of serotonin on glutamate release in dorsal medulla suppress
      systemic arterial pressure of cats.
AB  - The role of serotonin and glutamate release in dorsal medulla (DM) for regulation
      of systemic arterial pressure (SAP) was examined with microdialysis and high
      performance liquid chromatograph in anesthetized cats. KCl-perfusion in DM
      increased serotonin and glutamate concentrations in DM. Perfusion of serotonin
      resulted in decreases in glutamate concentration and SAP. Perfusion of
      alaproclate, a serotonin reuptake inhibitor that produced an increase in
      serotonin concentration in DM, had the same results as perfusion of serotonin. In
      conclusion, serotonin and glutamate appeared to be tonically and endogenously
      released from nerve terminals in DM, and the decrease in SAP could be attributed
      to the decreased glutamate release resulting from inhibitory action of serotonin
      in DM. The putative roles of serotonin and glutamate in DM may be important in
      SAP regulation.

PMID- 14729239
TI  - Diazepam reduces both arterial blood pressure and muscle sympathetic nerve
      activity in human.
AB  - It is known that benzodiazepines have a hypotensive effect, but the mechanism has
      not been well elucidated yet. To clarify whether this effect is due to central or
      peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to
      healthy volunteers and assessed the change in blood pressure, heart rate, muscle
      sympathetic nerve activity and heart rate variability. After diazepam
      administration, systolic and mean blood pressure decreased significantly. Muscle
      sympathetic nerve activity was also significantly reduced but heart rate did not
      change, whereas the variables of spectral analysis of heart rate variability did
      not show significant change. We concluded that the hypotensive effect of diazepam
      in human is mainly due to the central mechanism.

PMID- 14729241
TI  - Short-term high-frequency transcutaneous electrical nerve stimulation decreases
      human motor cortex excitability.
AB  - Several previous studies have shown that periods of changed sensory input can
      have after effects on the excitability of the corticospinal system. Here we test
      whether the parameters of peripheral stimulation conventionally used to treat
      pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have
      modulatory effects on the motor system. We measured the amplitude of motor evoked
      potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the
      right abductor pollicis brevis and first dorsal interosseous muscles before and
      after 30 min TENS over the right thenar eminence. In addition, we evaluated
      tactile and 2-point discrimination thresholds at the same site. TENS transiently
      reduced MEPs and increased sensory thresholds. This suggests that short-term TENS
      might have an inhibitory effect on both the sensory and motor systems.

PMID- 14729240
TI  - Age-related changes in histamine receptor mRNA levels in the mouse brain.
AB  - Several lines of evidence indicate that the histaminergic (HA) system is
      important for wakefulness and behavioral state regulation. We investigated the
      hypothesis that age-related changes in HA system occur which may be related to
      decreased alertness in aging. Although histidine decarboxylase mRNA levels did
      not change with age in C57BL/6 mice, significant differences were found in
      histamine H1 receptor (H1R), histamine H2 receptor (H2R), and histamine H3
      receptor (H3R) mRNA levels in several brain regions. The most widespread changes
      were observed in H1R mRNA, which were significantly lower (27-38%) in the cortex,
      hypothalamus, hippocampus and medulla of 24-month-old mice relative to 3-month
      old animals. Age-related changes in H2R mRNA levels were restricted to the pons
      and cerebellum and decreased H3R mRNA was found only in the medulla. In
      conjunction with the age-related decrease in hypocretin receptor 2 mRNA levels we
      have previously reported, decreased HA receptor mRNA levels may contribute to
      diminished alertness, sleep continuity, and diurnal rhythms of sleep and
      wakefulness in the aged.

PMID- 14729242
TI  - Expression of acyl-CoA hydrolase in the developing mouse brain.
AB  - Brain acyl-CoA hydrolase (BACH) is a cytosolic enzyme responsible for the brain
      long-chain acyl-CoA thioesterase activity, that is the highest in the body. BACH
      was detected in the mouse brain as early as embryonic day (E) 11.5 by
      immunoblotting. The level of the major isoform (43-kDa) was low until E12.5, but
      promptly elevated to a peak 7 days after birth. Thereafter, it declined somewhat
      and reached a steady-state level in adulthood. These changes in BACH expression
      were approximately reflected in the palmitoyl-CoA hydrolyzing activity in the
      developing mouse brain, and the time course was quite similar to that of
      microtubule-associated protein 2 (MAP2) expression. In immunohistochemistry of
      E14.5 embryo brains, cells expressing BACH almost coincided with the cells
      committed to the neuronal lineage, which expressed MAP2 but not nestin. These
      results indicate that BACH expression is induced during embryogenesis in
      association with neuronal differentiation, and persists after terminal
      differentiation into neurons in postnatal stages, resulting in the constitutive
      high expression of BACH in the adult brain in a neuron-specific manner.

PMID- 14729244
TI  - The human brain processes repeated auditory feature conjunctions of low
      sequential probability.
AB  - The human brain is known to preattentively trace repeated sounds as holistic
      entities. It is not clear, however, whether the same holds true if these sounds
      are rare among other repeated sounds. Adult humans passively listened to a
      repeated tone with frequent (standard) and rare (deviant) conjunctions of its
      three features. Six equiprobable variants per conjunction type were assigned from
      a space built from these features so that the standard variants (P=0.15 each)
      were not inseparably traceable by means of their linear alignment in this space.
      Differential scalp-recorded event-related potentials to deviants indicate that
      the standard variants were traced as repeated wholes despite their preperceptual
      distinctiveness and resulting rarity among one another.

PMID- 14729243
TI  - Perilesional pathological oscillatory activity in the magnetoencephalogram of
      patients with cortical brain lesions.
AB  - In the surrounding of focal ischemic brain lesions dysfunctional neuronal zones
      emerge often resulting in pathological oscillatory activity. Using whole-head
      magnetoencephalography we recorded brain activity during rest in 23 patients with
      ischemic cortical lesions to find out whether we can localise and characterise
      low-frequency oscillatory activity. We measured patients at different times after
      stroke and partly in a follow-up approach to determine the time course of slow
      wave activity. Using the analysis tool Dynamic Imaging of Coherent Sources we
      computed tomographic maps of oscillatory power in the delta-band (0.5-3 Hz).
      Fifteen of 23 patients with cortical strokes showed delta-activity, which was
      localised in an area not more than 2 cm away from the lesion. We found this
      perilesional low-frequency activity in the acute as well as in the chronic stage
      of stroke. Follow-up measurements of individual patients revealed persistence of
      perilesional low-frequency activity for months and even years. No consistent
      relation between perilesional activity and clinical symptoms was observed. Our
      results indicate that perilesional delta activity is common after ischemic
      cortical stroke. However, the functional significance remains to be elucidated.

PMID- 14729245
TI  - Chelation of synaptic zinc induces overexcitation in the hilar mossy cells of the
      rat hippocampus.
AB  - Complete removal of synaptic zinc by the chelator dietyldithiocarbamate (DEDTC;
      500 mg/kg i.p.) in rat was followed by convulsive behaviour including wet dog
      shakes alternating immobility. Histological analysis 1 day after DEDTC
      administration detected expression of heat shock protein in the hippocampus
      restricted to hilar cells. These cells colocalize the marker for neurons and the
      glutamate receptor GluR2/3 showing that they are excitatory neurons.
      Additionally, they projected to the contralateral dentate gyrus. Therefore, they
      correspond to hilar mossy cells. These data show that the synaptic zinc has a
      role in normal hippocampus avoiding overexcitation, that would impair
      functionality even in absence of pathological or exoexcitotoxic phenomena.

PMID- 14729246
TI  - Correlation between local monocarboxylate transporter 1 (MCT1) and glucose
      transporter 1 (GLUT1) densities in the adult rat brain.
AB  - Monocarboxylate transporters type 1 (MCT1) facilitate the transport of
      monocarboxylates across cell membranes of the blood-brain barrier and brain
      parenchymal cells. The present study had two aims: (1) to determine the local
      distribution of MCT1 in the brain; and (2) to compare the local densities of MCT1
      with the local densities of the main nutritional transporters, glucose
      transporter GLUT1. Using immunoautoradiography of cryosections from rat brain, 32
      brain structures were analyzed. (1) A heterogenous distribution pattern of MCT1
      densities was observed throughout the brain. Compared to brain homogenate (100%),
      MCT1 densities ranged from 43 to 164% in the brain structures investigated. Local
      GLUT1 densities showed a comparable range (35-145%). (2) A close correlation was
      found between local MCT1 and local GLUT1 densities. As local GLUT1 densities
      reflect local glucose metabolism in the brain, we conclude that local MCT1
      densities are adjusted to local glucose metabolism and transport.

PMID- 14729247
TI  - Subcellular localization of estrogen receptor beta in mouse hippocampus.
AB  - While estrogen receptors have been known to represent estrogen-dependent
      transcription factors as part of the nuclear receptor family, a putative membrane
      bound form of estrogen receptors has been suggested. Since estrogen receptor beta
      (ERbeta) is reportedly abundant in the hippocampus and other regions of the
      central nervous system, subcellular localization of ERbeta in mouse hippocampus
      was investigated. ERbeta was predominantly found in nuclear, synaptosomal and
      synaptic membrane fractions, particularly this last fraction. Immunocytochemical
      investigation using the NG108-15 neuroblastoma-glioma hybridoma cell line
      indicated that ERbeta is predominantly localized in cell membranes and nuclei.
      These results suggest that ERbeta localizes on synaptic membranes and may
      represent an important regulator of intracellular signal transduction from
      membrane to cytosol in hippocampal neurons.

PMID- 14729248
TI  - Thalamo-cortical projections to the posterior parietal cortex in the monkey.
AB  - Thalamo-cortical projections to the posterior parietal cortex (PPC) were
      investigated electrophysiologically in the monkey. Cortical field potentials
      evoked by the thalamic stimulation were recorded with electrodes chronically
      implanted on the cortical surface and at a 2.0-3.0 mm cortical depth in the PPC.
      The stimulation of the nucleus lateralis posterior (LP), nucleus ventralis
      posterior lateralis pars caudalis (VPLc), and nucleus pulvinaris lateralis
      (Pul.l) and medialis (Pul.m) induced surface-negative, depth-positive potentials
      in the PPC. The LP and VPLc projected mainly to the superior parietal lobule
      (SPL) and the anterior bank of the intraparietal sulcus (IPS), and the Pul.m
      mainly to the inferior parietal lobule (IPL) and the posterior bank of the IPS.
      The Pul.l had projections to all of the SPL, the IPL and both the banks. The
      significance of the projections is discussed in connection with motor functions.

PMID- 14729249
TI  - Effect of hypertonic saline on rat hypothalamic paraventricular nucleus
      magnocellular neurons in vitro.
AB  - The effect of hypertonic saline on rat hypothalamic paraventricular nucleus (PVN)
      magnocellular neurons was examined using a whole-cell patch-clamp technique.
      Under a current-clamp, 58/68 of magnocellular neurons were depolarized by
      hypertonic stimulation. Under a voltage-clamp, hypertonic saline produced an
      inward current via increased non-selective cationic conductance and shifting of
      the reversal potential to more positive values. Furthermore, hypertonic saline
      even without a change in osmolality increased spontaneous excitatory postsynaptic
      currents (sEPSCs). A bath application of CNQX almost completely blocked EPSCs.
      Extracellular application of gadolinium blocked the hypertonic saline- and
      mannitol-induced response. These results suggest that PVN magnocellular neurons
      are responsive to osmolality and Na+ concentrations. Hypertonic saline excited
      PVN magnocellular neurons via osmo-reception, Na+ -detection, and excitatory
      glutamatergic synaptic input.

PMID- 14729250
TI  - Activity in the dorsal cochlear nucleus of hamsters previously tested for
      tinnitus following intense tone exposure.
AB  - Chronic increases in spontaneous multiunit activity can be induced in the dorsal
      cochlear nucleus (DCN) of hamsters by intense sound exposure (Kaltenbach and
      McCaslin, 1996). It has been hypothesized that this hyperactivity may represent a
      neural code that could underlie the sound percepts of tinnitus. The goal of the
      present study was to determine whether hyperactivity could be demonstrated in
      animals that had previously been tested for tinnitus, and, if so, whether animals
      differing in their behavioral evidence for tinnitus also differ in their levels
      of spontaneous activity. The results showed not only that levels of activity in
      exposed animals were higher than those in control animals, but the degree to
      which the activity was increased was related to the strength of the behavioral
      evidence for tinnitus. These findings are consistent with the hypothesis that
      hyperactivity in the DCN may be a physiological correlate of noise-induced
      tinnitus.

PMID- 14729251
TI  - TorsinA, the gene linked to early-onset dystonia, is upregulated by the
      dopaminergic toxin MPTP in mice.
AB  - Early-onset torsion dystonias are caused by a mutation in TorsinA, a protein
      widely expressed in the nervous system. Here we report the cloning of the murine
      TorsinA cDNA and a mRNA in situ hybridization analysis of the expression patterns
      of TorsinA over developmental periods relevant to the etiology of early-onset
      dystonias. Several studies have demonstrated a functional involvement of the
      nigrostriatal dopaminergic system in pathological mechanisms underlying dystonia.
      In this study, we show that the expression of TorsinA is significantly increased
      in the brain within hours of treatment with the dopaminergic toxin, 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine in mice, suggesting that the TorsinA gene is
      regulated by cellular stress. These results provide insights into the
      pathophysiology of early-onset dystonia and strengthen links between the
      dopaminergic system and dystonia.

PMID- 14729252
TI  - Daily variations of blood glucose, acid-base state and PCO2 in rats: effect of
      light exposure.
AB  - The suprachiasmatic nuclei (SCN) of the hypothalamus are the site of the main
      circadian clock in mammals. Synchronization of the SCN to light is achieved by
      direct retinal inputs. The present study performed in rats transferred to
      constant darkness shows that blood glucose, pH and PCO2 display significant
      diurnal changes when measurements were made during the subjective day, the early
      subjective night or the late subjective night. The effects of a 30-min light
      exposure (100 lx) on these metabolic parameters at each of these circadian times
      were assessed. Regardless of the circadian time, light induced an increase in
      blood glucose, but did not affect plasma pH and PCO2. This study suggests that
      blood glucose, PCO2 and acid-base state are under circadian control, most likely
      mediated by the SCN, while the hyperglycemic response to light seems not to be
      gated by a circadian clock and may thus involve retinal inputs to non-SCN retino
      recipient areas.

PMID- 14729253
TI  - Multiminute oscillations in mouse substantia nigra pars reticulata neurons in
      vitro.
AB  - In acute slice of substantia nigra pars reticulata (SNr), a small proportion
      (6.6%) of GABAergic neurons exhibited abrupt increases in spontaneous firing rate
      from baseline frequency ( approximately 40 Hz) to peak (>100 Hz) with periods
      ranging in minutes when GABA(A) receptors were blocked by 20 microM bicuculline.
      The combination of GABA(B), non-NMDA, and NMDA blockers, SCH50911 (10 microM),
      6,7-dinitro-quinoxaline-2,3-dione (20 microM), and DL-2-amino-5-phosphonovalerate
      (50 microM), respectively, did not affect the incidence or properties of these
      multiminute oscillations, indicating that disinhibition induced by blockade of
      GABA(A) receptors is crucial in their generation. Incidence of oscillatory
      activity was increased to 16% by elevation of the K(+) concentration to 8 mM from
      basal level (6.24 mM). The SNr neurons exhibiting oscillatory activity with the
      addition of bicuculline had shown irregular fluctuations in basal firing rate,
      while the non-oscillatory neurons had shown a more regular baseline firing
      pattern. This is the first in vitro report of oscillations in firing rate of
      multiminute range in basal ganglia.

PMID- 14729254
TI  - Identification of live hair cells in rat cochlear sections in culture with FM1-43
      fluorescent dye.
AB  - Cochlear hair cells are presumed to live in culture for many days, yet they are
      difficult to identify in cultured tissues. We stained hair cells in cochlear
      sections with FM1-43 and cultured them in collagen matrix. Three rows of outer
      hair cells and a single row of inner ones were distinguished by staining with FM1
      43. Fixation of the sections with paraformaldehyde caused loss of the FM1-43
      fluorescence, indicating that FM1-43 stained only live hair cells. In sections
      cultured for 48 h, almost all hair cells were still positive with FM1-43. Culture
      with gentamycin caused loss of FM1-43-positive cells. In serum-free, long-term
      cultures (15 days) performed without antibiotics or neurotrophins, the row
      alignment of FM1-43-positive hair cells was still maintained. Membranous
      labyrinth-like vacuoles enveloping hair cells were formed in the collagen matrix.
      Accordingly, FM1-43 is an efficient marker for identifying live hair cells in
      cultured tissues. Moreover, cochlear hair cells are revealed to live for weeks in
      serum-free culture without exogenous neurotrophins.

PMID- 14729255
TI  - Localization of dopamine D1-receptor to A-type horizontal cells in the rabbit
      retina by single cell RT-PCR.
AB  - Dopamine is an important neurotransmitter regulating light-dark adaptation in the
      retina. The effect of dopamine is widespread and dependent on the localization of
      its receptors. We performed single cell RT-PCR on A-type horizontal cells
      visually selected from dissociated rabbit retinal neurons. Dopamine D1-receptor
      mRNA was positively identified. Subsequent sequencing of the fragment showed 82%
      homology with rat D1 receptor and 87% homology with human D1 receptor. This study
      supported previous observations that dopamine regulated A-type horizontal cell
      coupling via D1 receptors at the level of transcription.

PMID- 14729256
TI  - Lack of a genetic association between the TNXB locus and schizophrenia in a
      Chinese population.
AB  - A recent study demonstrated that the tenascin X (TNXB) gene was associated with
      schizophrenia in a British population. To replicate the initial finding, we
      analysed two positive single nucleotide polymorphisms (SNPs), rs1009382 and
      rs204887 present at the TNXB locus, in a Chinese population by using PCR-based
      restriction fragment length polymorphism analysis. We recruited a total of 136
      family trios consisting of fathers, mothers and affected offspring with
      schizophrenia. The transmission disequilibrium test did not show allelic
      association between these two SNPs and schizophrenia, and the rs1009382-rs204887
      haplotypes were not associated with the illness either. The present results
      suggest that the TNXB locus does not appear to be associated with schizophrenia
      in the Chinese population. Because the TNXB gene is less than 100 kb away from
      the NOTCH4 locus that was also reported to be associated with schizophrenia,
      allelic and locus heterogeneity could be possible reasons for the failure to
      replicate the TNXB finding.

PMID- 14729257
TI  - Age-dependence of the effect of treadmill exercise on cell proliferation in the
      dentate gyrus of rats.
AB  - The impact of age on the effect of treadmill exercise on cell proliferation in
      the dentate gyrus of rats was investigated via 5-bromo-2'-deoxyuridine
      immunohistochemistry. Animals of different ages were used: 4-week-old, 8-week
      old, and 62-week-old. Based upon the present study, the most prominent cell
      proliferation in the dentate gyrus was observed in the 4-week-old rats, and
      decreased in direct relation to the age of the animals. In addition, although
      treadmill exercise increased cell proliferation in the dentate gyrus of animals
      in all age groups, the most potent enhancing effect appeared in the 8-week-old
      rats. The present results demonstrate that age is an important factor in the
      regulation of cell proliferation in the dentate gyrus and that the enhancing
      effect of the treadmill exercise on cell proliferation also depends on age
      status.

PMID- 14729258
TI  - Nuclear organization and the control of HIV-1 transcription.
AB  - The regulation of transcription of the human immunodeficiency virus (HIV) is a
      complex event of significant pathological relevance, which recapitulates general
      concepts of cellular transcription with some peculiarities. The viral promoter is
      embedded in a chromatin structure that exerts powerful repression on
      transcription; activation of gene expression relies on the combined activity of a
      series of cellular factors that respond to different external stimuli, and on the
      function of a single viral regulatory protein, the Tat transactivator.
      Transcriptional activation is consequent to both chromatin remodeling and to the
      recruitment of elongation-competent RNA polymerase II complexes onto the
      integrated promoter, two events that require the coordinate, but transient,
      assembly of different protein complexes. Application of optical imaging
      techniques now allows us to appreciate the spatial and temporal evolvement of
      these reactions in vivo. The picture that is emerging is not only descriptive,
      but also relevant to the understanding of the regulation of the process. In
      particular, it appears that the confinement of biomolecules within specific
      subcellular compartments represents a way to control and coordinate the assembly
      of functional complexes that regulate viral gene expression.

PMID- 14729259
TI  - Ordered origin of the typical two- and three-repeat Myb genes.
AB  - Myb domain proteins contain a conserved DNA-binding domain composed of one to
      four conserved repeat motifs. In animals, Myb proteins are encoded by a small
      gene family and commonly contain three repeat motifs (R1R2R3); whereas, plant Myb
      proteins are encoded by a very large and diverse gene family in which a motif
      containing two repeats (R2R3) is the most common. In contrast to the conservation
      in the Myb domain, other regions of Myb proteins are highly variable. To explore
      the evolutionary origin of Myb genes, we cloned and sequenced Myb domains from
      maize and sorghum, and conducted a comprehensive phylogenetic analysis of Myb
      genes. The results indicate that the origins of individual Myb repeats are
      strikingly distinct, and that the R2 repeat has evolved more slowly than the R1
      and R3 repeats. However, it is not clear which repeat is the most ancient one.
      The evidence also suggests that R2R3 and R1R2R3 Myb genes co-existed in
      eukaryotes before the divergence of plants and animals. Based on our results, we
      propose that R1R2R3 Myb genes were derived from R2R3 Myb genes by gain of the R1
      repeat through an ancient intragenic duplication; this gain model is more
      parsimonious than the previous proposal that R2R3 Myb genes were derived from
      R1R2R3 Mybs by loss of the R1 repeat. A separate group of diverse non-typical Myb
      proteins exhibits a polyphyletic origin and a complex evolutionary pattern.
      Finally, a small group of ancient Myb paralogs prior to the amplification of
      current Myb genes is identified. Together, these results support a new model for
      the ordered evolution of Myb gene family.

PMID- 14729260
TI  - A conserved truncated isoform of the ATR-X syndrome protein lacking the SWI/SNF
      homology domain.
AB  - Mutations in the ATRX gene cause a severe X-linked mental retardation syndrome
      that is frequently associated with alpha thalassemia (ATR-X syndrome). The
      previously characterized ATRX protein (approximately 280 kDa) contains both a
      Plant homeodomain (PHD)-like zinc finger motif as well as an ATPase domain of the
      SNF2 family. These motifs suggest that ATRX may function as a regulator of gene
      expression, probably by exerting an effect on chromatin structure, although the
      exact cellular role of ATRX has not yet been fully elucidated. Here we
      characterize a truncated (approximately 200 kDa) isoform of ATRX (called here
      ATRXt) that has been highly conserved between mouse and human. In both species,
      ATRXt arises due to the failure to splice intron 11 from the primary transcript,
      and the use of a proximal intronic poly(A) signal. We show that the relative
      expression of the full length and ATRXt isoforms is subject to tissue-specific
      regulation. The ATRXt isoform contains the PHD-like domain but not the SWI/SNF
      like motifs and is therefore unlikely to be functionally equivalent to the full
      length protein. We used indirect immunofluorescence to demonstrate that the full
      length and ATRXt isoforms are colocalized at blocks of pericentromeric
      heterochromatin but unlike full length ATRX, the truncated isoform does not
      associate with promyelocytic leukemia (PML) nuclear bodies. The high degree of
      conservation of ATRXt and the tight regulation of its expression relative to the
      full length protein suggest that this truncated isoform fulfills an important
      biological function.

PMID- 14729261
TI  - Genomic organization and regulation of the LeIMP-1 and LeIMP-2 genes encoding myo
      inositol monophosphatase in tomato.
AB  - Myo-inositol (inositol) monophosphatase (IMP), an enzyme which catalyzes the
      synthesis of free inositol from various inositol monophosphates, is encoded by a
      small multigene family in many organisms. The tomato IMP gene family encodes
      three IMP isoforms with identical in vitro biochemical properties. To determine
      the role of each tomato LeIMP gene in plant growth, we isolated the genomic DNA
      copies of the LeIMP-1 and LeIMP-2 genes. The LeIMP-1 gene spans approximately 5.8
      kb and consists of 12 exons, whereas the LeIMP-2 gene consists of an
      uninterrupted, single open reading frame (ORF). We have previously shown that
      steady-state levels of LeIMP-2 mRNA were very low in comparison to LeIMP-1 and
      LeIMP-3 mRNA levels. To determine whether LeIMP-2 gene expression was spatially
      restricted to a discreet domain within the plant we constructed transgenic plants
      containing an LeIMP-2 promoter::uidA gene fusion. Analysis of transgenic
      seedlings revealed that the LeIMP-2 promoter directed gene expression within
      epidermal and cortex cells of specific stem/leaf junctions in an abaxial-specific
      pattern and in the shoot apical meristem. Further, inositol, the product of IMP
      catalysis, and Li+, an inhibitor of IMP catalysis, decreased expression of the
      LeIMP-2 promoter as measured by a decrease in beta-glucuronidase activity after
      treatment.

PMID- 14729262
TI  - Pattern of phylogenetic diversification of the Cychrini ground beetles in the
      world as deduced mainly from sequence comparisons of the mitochondrial genes.
AB  - The phylogenetic position of the tribe Cychrini within the subfamily Carabinae
      (the family Carabidae) was estimated by comparing the nucleotide sequences of the
      mitochondrial NADH dehydrogenase subunit 5 (ND5) gene and the nuclear 28S
      ribosomal DNA (rDNA). The phylogenetic trees suggest that the Cychrini would most
      probably be the oldest line within the Carabinae. Phylogenetic trees were
      constructed by comparing the mitochondrial cytochrome C oxidase subunit I (COI)
      gene sequences from 33 species of the Cychrini from various localities that
      include the whole distribution ranges of the representative species within all
      the known genera in the world. The trees suggest that the Cychrini members
      radiated into a number of phylogenetic lineages within a short period, starting
      about 44 million years ago (MYA). Most of the phylogenetic lineages or
      sublineages are geographically linked, each consisting of a single or only a few
      species without scarce morphological differentiation in spite of their long
      evolutionary histories (silent or near-silent evolution [see Adv. Biophys. 36
      (1999) 65; J. Mol. Evol. 53 (2001) 517]). The fact suggests that the geographic
      isolation per se did not bring about conspicuous morphological differentiation.
      The phylogenetic lineages of the Cychrini well correspond to the taxonomically
      defined genera and the subgenera.

PMID- 14729263
TI  - The SNF2 domain protein family in higher vertebrates displays dynamic expression
      patterns in Xenopus laevis embryos.
AB  - All eukaryotes share a common nuclear infrastructure, in which DNA is packaged
      into nucleosomal chromatin. Its functional states, in particular the
      accessibility of the chromatin fiber to trans-acting factors, are determined by
      two classes of evolutionarily conserved enzymes, i.e. histone modifying enzymes
      and ATP-driven nucleosome remodeling machines. Browsing the annotated human
      genome database, we establish here a family of SNF2-like nuclear ATPases, which
      are the core enzymatic subunits of chromatin remodeling protein complexes.
      Homologues of those human genes are also to a large extent found in the Xenopus
      laevis genome, indicating a high degree of sequence conservation of this family
      among vertebrates. Expression analyses of the ATPase family of proteins reveal
      stage- and tissue-specific domains of peak RNA expression during early frog
      embryogenesis. These dynamic expression profiles suggest specific functional
      requirements for individual members of this family throughout early stages of
      vertebrate development.

PMID- 14729264
TI  - Genomic structure, organisation, and promoter analysis of the bovine (Bos taurus)
      Mx1 gene.
AB  - Some MX proteins are known to confer a specific resistance against a panel of
      single-stranded RNA viruses. Many diseases due to such viruses are known to
      affect cattle worldwide, raising the possibility that the identification of an
      antiviral isoform of a bovine MX protein would allow the implementation of
      genetic selection programs aimed at improving innate resistance of cattle. With
      this potential application in mind, the present study was designed to isolate the
      bovine Mx1 gene including its promoter region and to investigate its genomic
      organisation and promoter reactivity. The bovine Mx1 gene is made up of 15 exons.
      All exon-intron boundaries conformed to the consensus sequences. A PCR product
      that contained a approximately 1-kb, 5'-flanking region upstream from the
      putative transcription start site was sequenced. Unexpectedly, this DNA region
      did not contain TATA or CCAAT motifs. A computer scan of the region disclosed a
      series of putative binding sites for known cytokines and transcription factors.
      There was a GAAAN(1-2)GAAA(C/G) motif, typical of an interferon-sensitive
      responsive element, between -118 and -107 from the putative transcription start
      site. There were also a NF-kappaB, two interleukin-6 binding sites, two Sp1 sites
      and five GC-rich boxes. The region also contained 12 stretches of the GAAA type,
      as described in all IFN-inducible genes. Bovine Mx1 expression was assessed by
      Northern blotting and immunofluorescence in the Madin Darby bovine kidney cells
      (MDBK) cell line treated with several stimuli. In conclusion, the bovine Mx1 gene
      and promoter region share the major structural and functional characteristics
      displayed by their homologs described in the rainbow trout, chicken, mouse and
      man.

PMID- 14729265
TI  - Putative protease inhibitor gene discovery and transcript profiling during fruit
      development and leaf damage in grapefruit (Citrus paradisi Macf.).
AB  - Seven putative protease inhibitor (PPI) cDNAs, representing four protein
      families, were isolated from a grapefruit (Citrus paradisi Macf. Cv. Marsh)
      immature fruit flavedo cDNA library. Cloned open reading frames encoded proteins
      with similarity to, and protein signatures for: legume Kuntiz inhibitors (lkiL-1,
      lkiL-2, lkiL-3), potato trypsin inhibitor I (ptiIL-1), serpins (serpL-1),
      cystatins (cystL-1), and gamma thionins (gthL-1). Response of transcript
      abundance to fruit development and leaf wounding was determined for all but lkiL
      1 using real-time RT-PCR. Immature leaves had the highest transcript levels for
      all PPIs. The gthL-1 transcript in immature leaves was the most abundant
      transcript but was absent from healthy mature leaves. In fruit flavedo,
      transcripts for all PPIs were most abundant in youngest fruit (<15 mm dia.
      fruit), and declined during development, but displayed different patterns of
      developmental change. Mechanical or Diaprepes root weevil (DRW) feeding damage to
      leaves caused a <10-fold reduction or had no effect on transcript level with the
      exception of gthL-1 which, as a result of damage, increased >50-fold in mature
      leaves and decreased >1400-fold in immature leaves. This developmental control of
      transcript response to wounding in a woody perennial is opposite of what has been
      observed for defensive proteinase inhibitors (PIs) in other plants (typically
      herbaceous and/or annual plants), where younger leaves typically invoke a higher
      defensive proteinase inhibitor transcript accumulation than older tissues. Except
      for gthL-1, the PPI transcripts were minimally responsive or unresponsive to
      wounding. Changes in PPI transcript levels suggest diverse roles for the products
      of these genes in citrus, with only gthL-1 responding in a defense-like manner.

PMID- 14729266
TI  - Brca1 expression is regulated by a bidirectional promoter that is shared by the
      Nbr1 gene in mouse.
AB  - The lack of functionally disrupting mutations of BRCA1 in sporadic breast tumours
      has suggested that other mechanisms, including dysregulation of gene expression,
      might be important in tumour development. We have analysed the control of
      expression of murine Brca1 and the adjacent gene, Nbr1, which lie head-to-head
      and are separated by less than 300 bp. Our results show that the expression of
      these two genes is under complex regulation, through a bidirectional promoter.
      Brca1 expression is driven by this single promoter, whereas Nbr1 expression is
      driven by this and one additional promoter, which generate two distinct
      transcripts, differing by the alternate use of the first exons. By comparison of
      mRNA transcription in adult murine tissues and also in the mammary gland during
      pregnancy and lactation, we show that Brca1 and Nbr1 expression is coordinately
      regulated in a spatial and temporal manner to produce quite different patterns of
      expression, even from the same promoter. The analysis of the murine and human
      syntenic region and its control has important implications for the regulation of
      human and murine BRCA1/NBR1 expression and the interpretation of animal models of
      disease.

PMID- 14729267
TI  - Identification of a developmentally regulated translation elongation factor 2 in
      Tetrahymena thermophila.
AB  - Protein synthesis elongation factor 2 (eEF2) catalyzes the translocation of the
      peptidyl-tRNA from the A site to the P site of the ribosome. Most organisms
      encode a single EF2 protein and its activity is regulated by phosphorylation. We
      have identified a family of genes in Tetrahymena thermophila that encode proteins
      homologous to eEF2, yet are expressed only during sexual reproduction. These
      genes have been designated EFR for Elongation Factor 2 Related. EFR transcripts
      were not detected in vegetative cell cultures but rapidly increased about 6 h
      after the start of conjugation (mating). For comparison, we cloned, sequenced and
      analyzed the expression of the standard eEF2 gene from T. thermophila. Unlike
      EFR, transcripts from eEF2 were detected in vegetative cells but were present at
      lower concentrations during conjugation. Despite the high sequence identity
      between EFR and eEF2 from other organisms (about 42% at the amino acid level),
      key regulatory sequences that are involved in the regulation of eEF2 are altered
      in EFR. The sequence and expression data suggest that EFR is an eEF2 variant
      involved in a major translation regulatory mechanism that occurs during the
      formation of the macronuclear genome in conjugating cells.

PMID- 14729268
TI  - Characterization of the Drosophila Rae1 protein as a G1 phase regulator of the
      cell cycle.
AB  - Messengers RNA (mRNA) are thought to be export from the nucleus as
      ribonucleoprotein complexes (mRNP), whose exact protein composition remains not
      completely determined. The Gle2/RAE1 protein, a highly conserved member of the
      WD40 repeat protein family, was first shown to be involved in mRNA export. More
      recently, a role in the cell cycle was also suggested. To get new insights into
      the functions of the metazoan protein, the Drosophila melanogaster rae1 (dmrae1)
      cDNA was first cloned, then the corresponding protein characterized and its
      function investigated by RNA interference. This paper shows that dmRae1 mainly
      localises to the nuclear membrane like its homologue in Saccharomyces cerevisiae.
      However, unlike its homologue and despite this particular sub-cellular
      distribution, its depletion does not impair the export of polyA+ RNAs.
      Interestingly, the presence of dmRae1 is important for normal proliferation and,
      more importantly, for the progression through the G1 phase of the cell cycle.
      Given that dmRae1 is closely related to the human form, results suggest that the
      human homologue, hsRAE1, may also play a similar role during the cell cycle.

PMID- 14729269
TI  - Heat-shock-responsive genes are not involved in the adult diapause of Drosophila
      triauraria.
AB  - Although the molecular regulation of diapause remains largely unknown, there is
      an accumulation of data suggesting the involvement of heat-shock proteins in the
      expression of diapause or dormancy. However, Goto et al. [J. Insect Physiol. 44
      (1998) 1009] reported that Drosophila triauraria does not express Hsp70
      transcripts at normal temperatures, regardless of the diapause state. Here, we
      investigated the transcriptional regulation of other heat-shock-responsive genes
      (Hsp23, Hsp26, Hsp83 and Hsrw) in D. triauraria with relation to diapause. The
      results revealed that these genes are not regulated as a function of diapause,
      suggesting that they are not involved in the expression of diapause in this
      species.

PMID- 14729270
TI  - The genome of the early chordate Ciona intestinalis encodes only five cytoplasmic
      intermediate filament proteins including a single type I and type II keratin and
      a unique IF-annexin fusion protein.
AB  - We screened the recently established draft genome of the early chordate Ciona
      intestinalis for genes encoding cytoplasmic intermediate filament (IF) proteins.
      The draft of the tunicate/urochordate genome contains only the five genes (IF-A,
      IF-B, IF-C, IF-D and IF-F) previously established by cDNA cloning. Three of these
      IF proteins (IF-D, IF-C, IF-A) were shown to be orthologs of vertebrate IF
      subfamilies I to III while two proteins (IF-B, IF-F) seemed tunicate specific.
      This is now firmly established for protein IF-F since the genomic data show that
      it arises as a fusion protein with a C-terminal annexin domain, a feature not
      found before in the very large collection of metazoan IF proteins. The results
      also confirm the previous proposal that urochordates lack orthologs of vertebrate
      type IV IF proteins. We discuss the striking increase of IF complexity from 5
      tunicate to 65 human genes during chordate evolution. Thus the tunicate has a
      single keratin pair, which is expressed in the epidermis, while the human genome
      has at least 25 genes each for keratins I and keratins II. Finally there are four
      normal Ciona annexin genes in addition to the gene encoding the IF-annexin fusion
      proteins (IF-F).

PMID- 14729271
TI  - Isolation and characterization of the canine serotonin receptor 1B gene (htr1B).
AB  - The serotonin receptor 1B gene (htr1B) has been suggested to be implicated in
      mental disorders in both humans and other species. We have isolated a canine
      bacterial artificial chromosome (BAC) clone containing htr1B, revealed the coding
      and surrounding DNA sequence of canine htr1B and designed primer sets for genomic
      sequencing of the gene. A mutation scan in 10 dogs revealed five single
      nucleotide polymorphisms in the htr1B coding sequence. By random sequencing of
      subclones of the BAC a polymorphic microsatellite repeat was found. We found
      evidence for at least four extended haplotypes in six dogs of the same breed. The
      chromosomal localization of the gene was confirmed by fluorescence in situ
      hybridisation and radiation hybrid mapping. This work provides a starting point
      for mutation scans and association studies on dogs with behavioural problems.

PMID- 14729272
TI  - Molecular systematics and evolution of the "Apollo" butterflies of the genus
      Parnassius (Lepidoptera: Papilionidae) based on mitochondrial DNA sequence data.
AB  - Sequences of 777 bp of mtDNA-ND5 locus were determined in order to shed light on
      the molecular systematics and evolution of the "Apollo" butterflies. Examined
      were nearly all of about 50 species of the genus Parnassius, together with seven
      species of the allied genera in the subfamily Parnassiinae (Papilionidae). The NJ
      and the MP phylogenetic trees show that the "Apollos" constitute a monophyletic
      group, comprising a number of cluster groups probably reflecting a relatively
      rapid radiation in evolution. The clusters of species-groups denoted I-VIII
      correspond to those species-groups recognized on the basis of morphological
      characters. Our findings will also help understand the biological relationships
      among several species or subspecies on which the classical taxonomy is in
      dispute. The unexpected finding is that among the samples of allied genera
      compared, Hypermnestra helios appears to be the most closely related to the
      "Apollos", despite morphological and behavioral dissimilarity. Furthermore, in
      contrast to the previous higher taxonomy, Archon apollinus which is classified in
      the tribe Parnassiini was found genetically closer to the tribe Zerynthiini,
      raising a taxonomic controversy.

PMID- 14729273
TI  - Identification of a region within SEL1L protein required for tumour growth
      inhibition.
AB  - The ectopic expression of the entire SEL1L cDNA significantly reduces the
      proliferate activity and aggressive behavior of the human breast carcinoma cell
      line MCF-7. However, the mechanism responsible for this biological effect remains
      unclear. A study was initiated to define those regions within SEL1L conferring
      such antiproliferative properties. Here we report that the region between amino
      acid residues 659-794 contains a functionally relevant domain since a deletion
      mutant impairs SEL1L's ability to suppress tumor cell growth. This region
      contains the Hrd3 motif, tetratricopeptide (TPR)-like SEL1 repeat, a
      transmembrane region, and a proline-rich tail.

PMID- 14729274
TI  - Functional expression and characterization of Echinococcus granulosus thioredoxin
      peroxidase suggests a role in protection against oxidative damage.
AB  - A full-length cDNA sequence coding for Echinococcus granulosus thioredoxin
      peroxidase (EgTPx) was isolated from a sheep strain protoscolex cDNA library by
      immunoscreening using a pool of sera from mice infected with oncospheres. EgTPx
      expressed as a fusion protein with glutathione S-transferase (GST) exhibited
      significant thiol-dependent peroxidase activity that protected plasmid DNA from
      damage by metal-catalyzed oxidation (MCO) in vitro. Furthermore, the suggested
      antioxidant role for EgTPx was reinforced in an in vivo assay, whereby its
      expression in BL21 bacterial cells markedly increased the tolerance and survival
      of the cells to high concentrations of H2O2 compared with controls.
      Immunolocalization studies revealed that EgTPx was specifically expressed in all
      tissues of the protoscolex and brood capsules. Higher intensity of labelling was
      detected in many, but not all, calcareous corpuscle cells in protoscoleces. The
      purified recombinant EgTPx protein was used to screen sera from heavily infected
      mice and patients with confirmed hydatid infection. Only a portion of the sera
      reacted positively with the EgTPx-GST fusion protein in Western blots, suggesting
      that EgTPx may form antibody-antigen complexes or that responses to the EgTPx
      antigen may be immunologically regulated. Recombinant EgTPx may prove useful for
      the screening of specific inhibitors that could serve as new drugs for treatment
      of hydatid disease. Moreover, given that TPx from different parasitic phyla were
      phylogenetically distant from host TPx molecules, the development of antiparasite
      TPx inhibitors that do not react with host TPx might be feasible.

PMID- 14729275
TI  - A processed pseudogene contributes to apparent mule deer prion gene
      heterogeneity.
AB  - Pathogenesis and transmission of the prion disorders (transmissible spongiform
      encephalopathies, TSEs) are mediated by a modified isoform of the prion protein
      (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility
      to TSE have been identified in sheep, humans and possibly elk. Comparable data
      have not been derived for mule deer, a species susceptible to the TSE chronic
      wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3
      of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed,
      with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were
      heterozygous for a coding change (N/S) at codon 138 (bp 412) and a non-coding
      polymorphism at bp 418, and individual deer with three or four different alleles
      were identified a possible gene duplication was indicated. Analysis of BAC clones
      containing mule deer PRNP genes revealed a full length functional gene and a
      processed pseudogene. The pseudogene was characteristic of previously described
      retroelements, in that it lacks introns and is flanked by repeat sequences. Three
      alleles of the functional gene were identified, with coding changes only at
      codons 20 (D/G) and 225 (S/F). Determination of PRNP functional gene alleles from
      47 CWD-positive mule deer showed the predominant allele encoded 20D225S
      (frequency 0.85). When alleles were grouped by coding changes in the functional
      gene, four of the six possible peptide combinations were identified in infected
      deer. Three pseudogene alleles with coding changes in exon 3 were identified in
      the mule deer samples examined. Because the TSEs appear to be "protein only"
      disorders, the presence of an untranslated pseudogene is not expected to affect
      disease resistance. Therefore, selection of a genotyping method specific for the
      functional gene is critical for large-scale studies to identify the role of the
      PRNP gene in susceptibility to CWD in mule deer.

PMID- 14729276
TI  - Cloning, genomic organization, expression, and effect on beta-casein promoter
      activity of a novel isoform of the mouse Oct-1 transcription factor.
AB  - The ubiquitously expressed transcription factor Oct-1, a member of the POU domain
      factors, is involved in the regulation of expression of many tissue-specific and
      house-keeping genes. Multiple alternatively spliced isoforms of Oct-1 have been
      identified in human and mouse cells. The expression patterns of these isoforms
      and the analysis of their genomic organization and structure have suggested that
      the structural variation of Oct-1 isoforms may be important in conferring target
      and tissue specificity to its transcriptional activity. In this study, we have
      cloned and sequenced a new mouse Oct-1 isoform, named mOct-1Z. This novel isoform
      differs markedly at the C-terminus from the previously identified Oct-1 isoforms
      A, B, and C. It is generated by alternative splicing from the Oct-1 gene and its
      transcript exhibits a frameshift followed by an early stop codon, thus, its
      predicted protein has a distinct, much shorter C-terminal tail. However, this
      truncated isoform could still effectively bind to a consensus Oct-1 motif
      oligonucleotide and, like Oct-1B, activated the basal promoter activity of the
      mouse beta-casein gene. Oct-1Z is another ubiquitously expressed Oct-1 isoform,
      its transcript being detected in all mouse tissues examined, including the
      mammary gland, liver, lung, kidney, spleen, small intestine mucosa, uterus, and
      ovary.

PMID- 14729278
TI  - What does a molecule want? The myth of the self-replicating molecule (comments on
      the "selfish-gene" paradigm).
AB  - The non-equilibrium statistical mechanical autocatalytic theory, underlying the
      "selfish-gene" paradigm, is shown to be at several points insufficient and
      contradictory for the description of observed facts of biological systems. We
      analyze at some length these deficiencies as (1) statistical versus individual
      non-linear self-constraints, (2) the continuous versus discrete cause-effect
      evolutional transition, and (3) the nature of the emerging aim-directed
      biological systems. Concerning the latter, it is shown that it can only be
      described with reference to the origin of the genetic code, which cannot be
      accounted for by the continuous evolution of non-equilibrium statistical
      mechanical systems. We point out that these deficiencies might be covered by
      alternative (quantum) theoretical considerations. The theory of evolution
      according to which may have lead to aim-directedness in the primordeal times in a
      more consistent way, concerning both phenotype and genotype. The specific
      physical model adopted is an affine Hilbert spaces scheme, with a naturally
      emerging internal dynamics of measurement, monitored internally by (time
      inversion) symmetry restoration. In this context, the physical relation of
      internal molecular symbolism (semiosis) and internal quantum mechanics is
      discussed.

PMID- 14729277
TI  - Cloning and partial characterization of four plasmalemmal-associated syntaxin
      isoforms in Limulus.
AB  - We describe herein the cloning of a group of syntaxins in Limulus that are
      associated with the plasma membrane. Initially, multiple degenerate
      oligonucleotide primers (DOP) and probes were designed from sequences of known
      plasma membrane associated syntaxins. Combined experiments using reverse
      transcriptase-polymerase chain reaction (RT-PCR), colony hybridization and
      reverse dot blot yielded three distinct probes. Subsequently, two cDNA libraries
      derived from the Limulus central nervous system (CNS) were screened and four
      distinct isoforms, designated Limulus syntaxin (Lim-syn) 1A, 1B, 1C and 1D, were
      obtained from forty cloned full-length sequences. The predicted amino acid (aa)
      sequences 1-265 were identical for Lim-syn 1A, 1C and for Lim-syn 1B, 1D,
      respectively. A comparison of the 265 aa cytoplasmic segments for the two
      subgroups Lim-syn 1A/1C and Lim-syn 1B/1D differed at 13 aa residues within this
      sequence. Lim-syn 1A and 1B contained 290 aa residues, and both contained a
      transmembrane domain (TMD, 267-288) and a myristylation-like site (286-290) at
      the C-termini. Lim-syn 1C (291 residues) contained only the TMD whereas Lim-syn
      1D was truncated (277 residues) and had neither a TMD nor a myristylation-like
      site. All Lim-syn isoforms showed great identity with syntaxin 1-homologs
      (syntaxin 1A/1B) from various other species. Ribonuclease protection assay (RPA)
      analyses revealed distinctive expression patterns for individual Lim-syn
      transcripts but all were detectable in the CNS. Moreover, the antibody (anti-Lim
      syn-1) produced against aa 133-145 epitope of Lim-syn identified a protein of
      approximately 35 kDa found only in CNS tissues.

PMID- 14729279
TI  - A computational model of a class of gene networks with positive and negative
      controls.
AB  - This article proposes a computational framework for modelling the logical
      behavior of a class of gene networks. We characterize the basic behavior of genes
      in terms of a state-and-transition structure, and model the individual genes as
      language-generating automata. We consider positive and negative controls as the
      interaction mechanisms among the genes, and treat such controls as constraints
      (also expressed in automata) imposed on the behavior of the gene network. By
      computing the intersection of the languages generated by the gene models and the
      constraints, we obtain the complete set of pathways in a gene network.
      Implications and possible improvement of this work are discussed.

PMID- 14729280
TI  - A biophysical model of vertebrate olfactory epithelium and bulb exhibiting gap
      junction dependent odor-evoked spatiotemporal patterns of activity.
AB  - This work describes a biophysical model of the initial stages of vertebrate
      olfactory system containing structures representing the olfactory epithelium and
      bulb. Its main novelty is the introduction of gap junctions connecting neurons
      both in the epithelium and bulb, and of biologically detailed dendrodendritic
      synapses between granule and mitral cells in the bulb. The model was used to
      simulate the effect of an odor presentation on the neural activity pattern in the
      epithelium and bulb. During the time for which an odor is presented with a
      constant concentration, there are spatiotemporal patterns in the epithelium and
      bulb generated by the couplings due to the gap junctions and/or dendrodendritic
      synapses. A study varying the strength of the gap junction coupling shows that
      the spatiotemporal patterns, both in the epithelium and bulb, are dependent of
      the coupling strength. It is also shown that the olfactory bulb's spatiotemporal
      pattern depends on the existence of the dendrodendritic connections between
      mitral and granule cells. If these spatiotemporal patterns really exist in the
      early processing stages of the olfactory system they may be used for odor coding
      and the gap junctions and dendrodendritic synapses might have a role on it.

PMID- 14729281
TI  - Robust and emergent Physarum logical-computing.
AB  - There have been many attempts for realization of emergent computing, but the
      notion of emergent computing is still ambiguous. In an open system, emergence and
      an error cannot be specified distinctly, because they are dependent on the dis
      equilibration process between local and global behaviors. To manifest such an
      aspect, we implement a Boolean gate as a biological device made of slime mold
      Physarum polycephalum. A Physarum (slime mold) Boolean gate could be an
      internally instable machine, while it has the potential for emergent computing.
      First, we examined whether Physarum Boolean gate works properly, and then
      examined its behaviors when the gate is collapsed in terms of hardware. The
      behavior of Physarum changes and self-repairing computing is achieved as a
      result. The self-repairing against internal failure is one of attributes of
      emergent and robust computing.

PMID- 14729282
TI  - Time hierarchies in the Escherichia coli carbohydrate uptake and metabolism.
AB  - The analysis of metabolic pathways with mathematical models contributes to the
      better understanding of the behavior of metabolic processes. This paper presents
      the analysis of a mathematical model for carbohydrate uptake and metabolism in
      Escherichia coli. It is shown that the dynamic processes cover a broad time span
      from some milliseconds to several hours. Based on this analysis the fast
      processes could be described with steady-state characteristic curves. A
      subsequent robustness analysis of the model parameters shows that the fast part
      of the system may act as a filter for the slow part of the system; the
      sensitivities of the fast system are conserved. From these findings it is
      concluded that the slow part of the system shows some robustness against changes
      in parameters of the fast subsystem, i.e. if a parameter shows no sensitivity for
      the fast part of the system, it will also show no sensitivity for the slow part
      of the system.

PMID- 14729283
TI  - A "chimera" theory on the origin of dicyemid mesozoans: evolution driven by
      frequent lateral gene transfer from host to parasite.
AB  - The phylogenetic status of the enigmatic dicyemid mesozoans is still uncertain.
      Are they primitive multicellular organisms or degenerate triploblastic animals?
      Presently, the latter view is accepted. A phylogenetic analysis of 18S rDNA
      sequences placed dicyemids within the animal clade, and this was supported by the
      discovery of a Hox-type gene with a lophotrochozoan signature sequence. This
      molecular information suggests that dicyemid mesozoans evolved from an ancestral
      animal degenerately. Considering their extreme simplicity, which is probably due
      to parasitism, they might have come from an early embryo via a radical
      transformation, i.e. neoteny. Irrespective of this molecular information,
      dicyemid mesozoans retain many protistan-like or extremely primitive features,
      such as tubular mitochondrial cristae, endocytic ability from the outer surface,
      and the absence of collagenous tissue, while they do not share noticeable
      synapomorphy with animals. In addition, the 5S rRNA phylogeny suggests a somewhat
      closer kinship with protozoan ciliates than with animals. If we accept this clear
      contradiction, dicyemids should be regarded as a chimera of animals and
      protistans. Here, we discuss the traditional theory of extreme degeneration via
      parasitism, and then propose a new "chimera" theory in which dicyemid mesozoans
      are exposed to a continual flow of genetic information via eating host tissues
      from the outer surface by endocytosis. Consequently, many of their intrinsic
      genes have been replaced by host-derived genes through lateral gene transfer
      (LGT), implying that LGT is a key driving force in the evolution of dicyemid
      mesozoans.

PMID- 14729284
TI  - Communication and malpractice claims--where are we now?

PMID- 14729285
TI  - Improving patients' communication with doctors: a systematic review of
      intervention studies.
AB  - A systematic review of the literature examined intervention studies designed to
      increase patients' participation in medical consultations. Twenty-five papers
      describing twenty studies met the inclusion criteria. About half of the
      intervention studies were randomised placebo controlled experimental designs. The
      studies were predominantly conducted in outpatient or primary care settings, with
      50% of the interventions presented in a written form. Overall, half of the
      interventions resulted in increased patient participation, with slightly more
      significant results found for bids for clarification than question-asking.
      However, of the 10 written interventions only two reported a significant increase
      in question-asking. Patient satisfaction was the most commonly measured outcome,
      but few significant improvements were found. However, there were significant
      improvements in other outcomes, including perceptions of control over health,
      preferences for an active role in health care, recall of information, adherence
      to recommendations, attendance, and clinical outcomes. Few studies examined the
      links between patient characteristics and the success of the interventions.
      Future research needs to establish which forms of intervention are most effective
      and practical, for which groups of patients.

PMID- 14729286
TI  - Healthy living does not reduce life satisfaction among physically handicapped
      persons.
AB  - Smoking, drinking, over-eating and sedentary living may be regarded as ways of
      compensating for losses inflicted by physical handicaps. Therefore, promoting
      healthy life-styles among physically handicapped persons may amount to reducing
      their life satisfaction. This article examines the life-style and life
      satisfaction of all self-reported somatically handicapped respondents 25-50 years
      of age in a mid-Norwegian county. Persons with physical handicaps had more
      unhealthy habits than the general population. But life-style was not related to
      degree of physical handicap. And quality of life among the physically handicapped
      was not associated with life-style. Efforts to promote healthy living may not
      threaten the quality of life of physically handicapped persons.

PMID- 14729287
TI  - Preparing patients for gastrointestinal endoscopy: the influence of information
      in medical situations.
AB  - The effects of the provision of information were tested in a sample of patients
      who underwent a gastrointestinal endoscopy for the first time (N=260). On the
      basis of their Threatening Medical Situation Inventory (TMSI)-monitoring score
      these patients were divided in high monitors versus low monitors. On the basis of
      the existing literature each group received the type of information that was
      considered most beneficial with regard to their coping style, and each group was
      compared with a control group receiving standard care (the usual information plus
      coaching by a nurse). Dependent variables were anxiety at different points in
      time, heart rate and skin conductance, pain, experience of the procedure, course
      of the procedure, duration of gagging, and satisfaction with the information
      provided. Unexpectedly, it turned out that high monitors did not profit by
      extensive information when compared with high monitors receiving standard care.
      Also for low monitors their minimal informational intervention did not exceed the
      effects of standard care. In the discussion, four factors possibly responsible
      for these results were elaborated. It is concluded that reservedness is required
      in providing (too) extensive information to patients who ask for this.
      Furthermore, considering the rather unpredictable and uncontrollable course of a
      gastrointestinal endoscopy, coaching by a nurse remains a valuable type of
      support.

PMID- 14729288
TI  - Somatic complaints and isoniazid (INH) side effects in Latino adolescents with
      latent tuberculosis infection (LTBI).
AB  - This study examined the potential effects of INH side effects and non-specific
      somatic complaints on medication adherence in 96 Latino adolescents participating
      in a controlled trial designed to increase isoniazid (INH) adherence. These
      participants (who received usual medical care) were interviewed monthly over 9
      months. Participants were questioned regarding medication taking, the frequency
      of 15 INH-related side effects from the Physician's Desk Reference (PDR) [1], and
      21 non-specific somatic complaints. Participants were aged 12-19 years, 53.1%
      were male, 66.7% were born in Mexico, 73% had no health insurance, and 52.5% were
      classified as bicultural. Approximately 70% of participants experienced at least
      one side effect during the trial. Side effects that occurred while taking INH
      were not significantly related to total number of pills taken; somatic complaints
      that occurred during 9 months of INH were significantly negatively related to
      cumulative adherence. Females reported significantly more somatic complaints at
      baseline than males.

PMID- 14729289
TI  - Supporting the psychosocial needs of patients in general practice: the role of a
      voluntary referral service.
AB  - This qualitative study describes and analyses the key features of a practice
      based voluntary referral service called the Patient Support Service (PSS). This
      involved collecting interview data from 11 service users and 8 service providers,
      which was analysed using 'Framework,' a qualitative method of applied policy
      research. The study findings describe the PSS, its perceived effectiveness and
      barriers to service provision. Following this, a series of strategic
      recommendations for service development are presented. It is concluded that
      voluntary patient referral services, such as the PSS, broaden the referral
      options available for managing patients with psychosocial problems in primary
      care.

PMID- 14729290
TI  - Perceptions of cardiovascular risk among patients with hypertension or diabetes.
AB  - We aimed to examine risk perceptions among patients at moderate to high
      cardiovascular risk. A questionnaire about perceived absolute risk of myocardial
      infarction and stroke was sent to 2424 patients with hypertension or diabetes.
      Response rate was 86.3% and 1557 patients without atherosclerotic disease were
      included. Actual cardiovascular risk was calculated by using Framingham risk
      functions. A total of 363 (23.3%) of the 1557 patients did not provide any risk
      estimates and these were particularly older patients, patients with a lower
      educational level, and patients reporting no alcohol consumption. The remaining
      1194 patients tended to overestimate their risk. In 42.3% (497/1174) and 46.8%
      (541/1155) of the cases, patients overestimated their actual 10-year risk for
      myocardial infarction and stroke, respectively, by more than 20%. Older age,
      smoking, familial history of cardiovascular disease (CVD), and actual absolute
      risk predicted higher levels of perceived absolute risk. Male sex, higher scores
      for an internal health locus of control, lower scores for a physician locus of
      control, and self-rated excellent or (very) good health were positively related
      to higher accuracy. In conclusion, patients showed inadequate perceptions of
      their absolute risk of cardiovascular events and physicians should thus provide
      greater information about absolute risk when offering preventive therapy.

PMID- 14729291
TI  - Increasing knowledge about a screening test: preliminary evaluation of a
      structured, chart-based, screener presentation.
AB  - The provision and understanding of good quality information is one of the key
      characteristics of an informed choice. However, written materials alone often
      fail to achieve good understanding of screening tests. The present study
      describes the preliminary evaluation of a structured, chart-directed
      presentation, aimed at increasing knowledge of a screening test. Forty mothers of
      babies undergoing a newborn hearing test received either a standard, or a
      standard plus structured, presentation of the screening test. Standard
      presentation was a leaflet and short verbal explanation of the test. Structured
      presentation comprised an illustrated chart explaining the process and possible
      outcomes of screening, followed by screeners checking mothers understanding of
      key points and, if necessary, giving further explanation. After screening,
      maternal knowledge of the test was assessed using seven multiple choice items.
      Overall knowledge was high. For women with lower levels of education, the
      structured presentation resulted in significantly higher levels of knowledge than
      the standard presentation only.

PMID- 14729292
TI  - Pediatrician-parent-child communication: problem-related or not?
AB  - Pediatricians are generally confronted with a variety of health problems. Each of
      these problems may benefit from another pattern of healthcare communication. It
      is unknown whether the communication process during pediatric visits actually
      differs by the nature of the child's problem. This study first examined whether
      three formerly identified communication patterns could be distinguished within
      real-life pediatric outpatient encounters (N=846). Then, communication patterns
      during encounters with children with respiratory (n=269) or behavioral problems
      (n=77) were compared. Videotaped visits were observed using the Roter Interaction
      Analysis System. Two-level multivariate logistic regression analysis examined
      what factors contributed to the communication patterns. A biopsychosocial
      communication pattern was observed in 45%, a psychosocial in 15% and a biomedical
      pattern in 40% of the visits. Child's age and pediatrician's experience were
      related to the communication pattern. Different patterns did indeed prevail in
      respiratory and behavioral problems. As less experienced pediatricians attend to
      psychosocial issues less, they may have to be specifically encouraged to do so.

PMID- 14729293
TI  - Pathways to adult diagnosis of CF: the impact of pre-diagnosis experience on post
      diagnosis responses and needs.
AB  - This phenomenological study explored the pre-diagnosis experiences of 36 men and
      women who learned during their adult years that they had cystic fibrosis (CF), a
      disease usually diagnosed in children. Four mutually-exclusive pathways to
      diagnosis emerged during data analysis, each determined by the extent to which
      participants experienced symptoms growing up and the extent to which they
      suspected they had a serious disease. Themes describing the pathways were
      developed. Pre-diagnosis experiences were found to impact post-diagnosis
      experiences, as well as individuals' readiness for education, treatment, and
      support. Recommendations for CF caregivers, consistent with the expressed wishes
      of participants, also emerged. Findings revealed that, at least for CF, not all
      arrive at diagnosis having had similar experiences, suggesting individualized
      approaches to initiating treatment, education, and support. Although the
      literature largely conceptualizes chronic illness experience as beginning with
      diagnosis, this study highlights the pre-diagnosis period as an important focus
      for additional study.

PMID- 14729294
TI  - The impact of the preventive medical message on intention to change behavior.
AB  - Clinicians counsel patients to adopt behaviors to reduce health risks. We
      studied, in the case of coronary artery disease, the impact of those parts of the
      preventive medical message clinicians can vary. We asked 150 French people (86
      aged 20-30, 64 aged 60-80) to rate their intention to adopt a specific behavior
      take medication, change their diet, or start exercising-in 64 scenarios, composed
      of two severities of disease manifestations (angina pectoris or heart attack);
      four levels of its probability of occurrence (5, 10, 15, or 20%) and the
      associated time horizon (20, 15, 10, or 5 years, respectively); and two levels of
      controllability of the risk (entirely under your control or not much you can do
      to reduce it). We found that all four parts of the message had significant main
      effects and did not interact with each other. Older participants had greater
      intention to adopt preventive behavior when the time horizon was short and
      younger ones when it was long. The only gender effect was that older women were
      more sensitive to time horizon. The message's parts were combined additively.
      Participants intended to change behavior even when told this would be of little
      use. We concluded that clinicians should, when possible, discuss all key parts of
      the preventive medical message; that they can, however, focus on one without
      reducing the others' impact; and that, at least for outcomes such as angina and
      heart attack, they should speak of risk with young patients using a long time
      horizon, with old patients using a short time horizon.

PMID- 14729295
TI  - Menopausal hormone therapy decisions: insights from a multi-attribute model.
AB  - A multi-attribute utility (MAU) decision model for menopausal hormone replacement
      therapy (HRT) was developed using structured interviews (n=40) to identify
      decision factors, and a telephone survey (n=97) to ascertain utility scores.
      Utility scores for individual factors and composite scores reflecting the HRT
      decision were compared according to HRT use. Composite utility scores (range of 
      1.0 to 1.0, with higher values supporting HRT use) were 0.55, -0.27, and -0.19
      for the 48 HRT users, 23 former users, and 26 never users, respectively
      (P<0.0001). Among HRT current users, the main factors supporting use were
      concerns about heart disease, osteoporosis, and symptoms of menopause. Among
      former users, side effects weighed heavily against use, and among never users
      breast cancer concerns weighed heavily against use. Linear regression methods
      were used to identify the utilities most predictive of current HRT use. The
      decision model provided insight regarding how personal expectations and values
      influence HRT use.

PMID- 14729296
TI  - Diabetes patient education: a meta-analysis and meta-regression.
AB  - Diabetes education has largely been accepted in diabetes care. The effect of
      diabetes education on glycemic control and the components of education
      responsible for such an effect are uncertain. We performed a meta-analysis of
      randomized controlled trials of diabetes patient education published between 1990
      and December 2000 to quantitatively assess and characterize the effect of patient
      education on glycated hemoglobin (HbA(1c)). Additionally, we used meta-regression
      to analyze which variables within an education intervention that best explained
      variance in glycemic control. Twenty-eight educational interventions (n=2439)
      were included in the analysis. The net glycemic change was 0.320% lower in the
      intervention group than in the control group. Meta-regression revealed that
      interventions which included a face-to-face delivery, cognitive reframing
      teaching method, and exercise content were more likely to improve glycemic
      control. Those three areas collectively explained 44% of the variance in glycemic
      control. Current patient education interventions modestly improve glycemic
      control in adults with diabetes. We highlight three potential components of
      educational interventions that may predict an increased likelihood of success in
      ameliorating glycemic control.

PMID- 14729297
TI  - Promoting patient participation in consultations: a randomised controlled trial
      to evaluate the effectiveness of three patient-focused interventions.
AB  - The aim of this experimental study was to evaluate the effectiveness of three
      patient-focused interventions designed to increase patient question asking in
      clinical consultations. Patients were randomly allocated to one of five
      conditions to receive either one of three interventions or to serve as an
      attention control group or a control group. The primary outcome measure was
      question asking by the patient of their physician. Participants in the
      intervention groups did not ask more questions than participants in the control
      groups. Immediately after the consultation participants in the intervention
      groups had higher levels of self-efficacy in asking questions. Three months after
      the index visit patients in the intervention groups were significantly more
      likely to be satisfied to some degree than patients in the control group. There
      was no difference in diabetic control. These results suggest that simple brief
      patient-focused interventions do not change patient behaviour in medical
      outpatient consultations.

PMID- 14729298
TI  - Empowering communication: a community-based intervention for patients.
AB  - The "How to Talk to Your Doctor" community education forums operate under the
      assumption that information exchange and consumer involvement in healthcare can
      empower communities in need. We report on the development and preliminary
      evaluation of this community-based intervention designed to activate and enhance
      patients' communicative abilities in the medical encounter. We review evidence
      supporting the feasibility of and benefits that can be expected from improving
      patients' communication competency. Our intervention is simple and flexible so,
      therefore, can be portable to a large number of communities. Our preliminary
      evaluation suggests that the intervention is well-received and produces improved
      self-perceptions of communication competence across diverse settings and
      participants. We describe our intervention and its development and dissemination
      as a model for improving patients' communicative abilities through a community
      based, active learner approach. By sharing our experiences, the barriers we
      encountered, and our ongoing efforts to improve patient communication in the
      medical encounter, we hope to empower patients to communicate better with their
      physicians.

PMID- 14729299
TI  - Strong protective action of Copper(II) N-substituted sulfonamide complexes
      against reactive oxygen species.
AB  - Copper(II) complexes of N-benzothiazolsulfonamides, [Cu(N-2-(5,6
      dimethylbenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (1), [Cu(N-2-(6
      chlorobenzothiazole)benzenesulfonamidate)(2)(dmso)(2)] (2) and [Cu(N-2-(6
      chlorobenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (3) with interesting
      protective properties against superoxide radicals have been prepared. The
      compounds have been characterized by X-ray diffraction and their chemical
      properties have been studied by spectroscopic methods. The crystal structure of 1
      shows that the copper(II) is surrounded by two benzothiazole N atoms from the
      sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a
      square planar arrangement. The coordination polyhedron around copper(II) in 2 and
      3 is distorted square pyramidal being the metal ion linked to benzothiazole N and
      sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The
      three complexes have a strong protective action over Delta sod1 mutant of
      Saccharomyces cerevisiae against reactive oxygen radicals derived from
      respiration and against those generated by hydrogen peroxide and menadione.

PMID- 14729300
TI  - Synergistic anion-directed coordination of ferric and cupric ions to bovine serum
      transferrin--an inorganic perspective.
AB  - A series of new iron(III) and copper(II) complexes of bovine serum transferrin
      (BTf), with carbonate and/or oxalate as the synergistic anion, are presented. The
      complexes [Fe(2)(CO(3))(2)BTf], [Fe(2)(C(2)O(4))(2)BTf], [Cu(2)(CO(3))(2)BTf] and
      [Cu(C(2)O(4))BTf] were prepared by standard titrimetric techniques. The oxalate
      derivatives were also obtained from the corresponding carbonate complexes by
      anion-displacement. The site-preference of the transition metal-oxalate synergism
      has facilitated the preparation and isolation of the mononuclear complex
      [Cu(C(2)O(4))BTf], the mixed-anion complexes [Cu(2)(CO(3))(C(2)O(4))BTf] and
      [Fe(2)(CO(3))(C(2)O(4))BTf] and the mixed-metal complex [FeCu(C(2)O(4))(2)BTf].
      The sensitivity of electron paramagnetic resonance (EPR) spectroscopy to the
      nature of the synergistic anions at the specific-binding sites of the
      transferrins has made this physical technique particularly indispensable to this
      study. None of the other members of the transferrin family of proteins has ever
      been demonstrated to bind the ferric and cupric ions one after the other, each
      occupying a separate specific-binding site of the same transferrin molecule, as a
      response to the coordination restrictions imposed by the oxalate ion. The
      bathochromic shift of the visible p(pi)-d(pi*) CT band for iron(III)-BTf and the
      hypsochromic shift of the p(pi)-d(sigma*) CT band for copper(II)-BTf, on
      replacing carbonate by oxalate as the associated anion, are consistent with the
      relative positions of these anionic ligands in the spectrochemical series and the
      nature of the d-type acceptor orbitals involved in the CT transitions. The
      binding and spectroscopic properties of bovine serum transferrin--a serum
      transferrin--very nearly mirror those of human serum transferrin, but differ
      significantly from those of human lactoferrin.

PMID- 14729301
TI  - Succinylhydroxamic derivatives of alpha-amino acids as MMP inhibitors. Study of
      complex-formation equilibria with Cu2+, Ni2+ and Zn2+.
AB  - A series of Pro- and Phe-succinyl hydroxamate derivatives, whose nanomolar
      inhibitory activity towards a series of matrix metalloproteinases (MMPs) was
      previously reported, have been studied and described herein in their interaction
      with Cu(2+), Zn(2+), Ni(2+) in aqueous solution, by using potentiometric,
      spectroscopic and ESI-MS (electrospray ionization mass) spectrometric techniques.
      A systematic study at various ligand-to-metal molar ratios allowed the
      determination of the stability constants of the complexes as well as the
      estimation of the coordination modes. The similarity in the biological activity
      of these compounds seems to be paralleled by the identical metal-complexation
      behaviour at neutral pH, namely in terms of chelating effectiveness and
      coordination modes, irrespective of the presence of one carboxylic or hydroxamate
      as extra groups, or also of the type of amino-acid residue at the other flank of
      the succinyl chain, which seems to be enough away from the succinyl hydroxamate
      metal-binding group. The stability order of the metal complexes with these
      ligands follows the Irving-Williams trend for this type of complex systems.
      Noteworthy is the identification of an interesting pentanuclear copper(II)
      species with the monohydroxamic ligands which structure was ascribed to a 12
      metallacrown-4.

PMID- 14729302
TI  - DNA binding and cleavage properties of certain tetrammine ruthenium(II) complexes
      of modified 1,10-phenanthrolines--effect of hydrogen-bonding on DNA-binding
      affinity.
AB  - A series of ruthenium(II) mixed ligand complexes of the type
      [Ru(NH(3))(4)(L)](2+), where L=imidazo[4,5-f][1,10]phenanthroline (ip), 2
      phenylimidazo[4,5-f][1,10]phenanthroline (pip), 2-(2-hydroxyphenyl)imidazo[4,5
      f][1,10]phenanthroline (hpip), 4,7-diphenyl-1,10-phenanthroline (dip),
      naphtha[2,3-a]dipyrido[3,2-h:2',3'-f]phenazine-5,18-dione (qdppz), 5,18
      dihydroxynaphtho[2,3-a]dipyrido[3,2-H:2',3'-f]phenazine (hqdppz), have been
      isolated and characterized. The interaction of these complexes with calf thymus
      DNA (CT DNA) has been explored by using absorption, emission, and circular
      dichroic spectral methods, thermal denaturation studies and viscometry. All these
      studies suggest the involvement of the modified phenanthroline 'face' rather than
      the ammonia 'face' of the complexes in DNA binding. An intercalative mode of DNA
      binding, which involves the insertion of the modified phenanthroline ligands in
      between the base pairs, is suggested. The results from absorption spectral
      titration and circular dichroism (CD), thermal denaturation and viscosity
      experiments indicate that the qdppz and hqdppz complexes (K(b) approximately
      10(6) and Delta T(m)=11-13 degrees C) bind more avidly than the ip, pip and hpip
      complexes (K(b) approximately 10(5), Delta T(m)=6-8 degrees C). Intramolecular
      hydrogen bonding in the hpip and hqdppz complexes increases the surface area of
      the intercalating diimines and enhances the DNA binding affinity substantially.
      The ammonia co-ligands of the complexes are possibly involved in hydrogen bonding
      with the intrastrand nucleobases to favour intercalation of the extended aromatic
      ligands. Circular dichroism spectral studies reveal that all the complexes effect
      certain structural changes on DNA duplex; [Ru(NH(3))(4)(ip)](2+) induces a B to A
      transition while [Ru(NH(3))(4)(qdppz)](2+) a B to Psi conformational change on CT
      DNA. Cleavage efficiency of the complexes were determined using pBR322
      supercoiled plasmid DNA. All the complexes, except hqdppz complex, promote the
      cleavage of supercoiled plasmid (form I) to relaxed circular form (form II).

PMID- 14729303
TI  - X-ray, spectral and biological (antimicrobial and superoxide dismutase) studies
      of oxalato bridged CuII-NiII and CuII-ZnII complexes with
      pentamethyldiethylenetriamine as capping ligand.
AB  - X-band electron spin resonance (ESR) and electronic spectra of oxalatobridged
      heterodinuclear Cu-Ni and Cu-Zn complexes, viz., [(PMDT)Cu-Ox
      Ni(PMDT)](BPh(4))(2).2CH(3)CN and [(PMDT)Cu-Ox-Zn(PMDT)](BPh(4))(2).2CH(3)CN,
      where PMDT=pentamethyldiethylenetriamine, Ox=oxalate ion have been described.
      Complex [(PMDT)Cu-Ox-Ni(PMDT)](BPh(4))(2).2CH(3)CN has been structurally
      characterized. This complex crystallizes in the monoclinic space group, C(2) (No.
      5) with the unit parameters a=20.445(4) A, b=14.884(3) A, c=23.174(5) A, alpha=90
      degrees, beta=102.693(4) degrees, gamma=90 degrees, V=6880(2) A(3) and Z=4. The
      structure refined to R=0.0354 and R(w)=0.0853 for 21,109 reflections with I>2
      sigma(I) using 765 parameters, shows the presence of a MN(3)O(2) chromophore in a
      distorted trigonal-bipyramidal (TBP) heterometallic complex with oxalate dianion.
      Taking with an equatorial Cu-O=2.137(8) A and an axial Cu-O=1.961(6) A
      coordination site at Cu(II) ion and equatorial Ni-O=2.178(7) A and axial Ni
      O=1.994 (9) A coordination site at Ni(II) ion. The Cu-Ni distance is 5.3532(9) A
      and Cu-C(2)O(4)-Ni unit is planar. The [(PMDT)Cu-Ox-Ni(PMDT)](2+) shows the ESR
      spectrum of the antiferromagnetic spin exchange with each dinuclear
      delocalization of the unpaired electron over the unit and spin-doublet ground
      state which demonstrates the Cu-Ox-Ni core. Antimicrobial and superoxide
      dismutase (SOD) activities of these complexes have also been measured.

PMID- 14729304
TI  - Voltammetric studies of the interaction between Re(V) complexes and proteins.
AB  - A reliable method based on electrochemical measurements for the evaluation of
      protein interaction with small electroactive coordination compounds is proposed.
      Protein binding capacity of five different cationic Re(V) complexes was evaluated
      by means of voltammetric techniques in the absence and the presence of bovine
      serum albumin. The percentage of interaction between the complex and the protein
      was estimated from the quantitative decrease of the diffusion coefficient for the
      sole complex due to the addition of the protein, and therefore the formation of
      the protein-complex molecular ensemble. The proposed methodology was checked
      using cisplatin as a molecular complex probe.

PMID- 14729305
TI  - Preferences of kanamycin A towards copper(II). Effect of the resulting complexes
      on immunological mediators production by human leukocytes.
AB  - The widespread presence of pathogenic bacteria is a cause of permanent demand for
      investigating the properties of antimicrobial agents. The chemical basis of
      several toxic effects induced by antibiotics still remains unclear.
      Aminoglycosides, highly ototoxic and nephrotoxic drugs, are capable of copper(II)
      ions chelating. In this study we established the affinity of kanamycin A towards
      copper(II), in contrast with other metal ions: iron(III), nickel(II), cobalt(II)
      and zinc(II) by means of potentiometry. Circular dichroism spectroscopy was
      applied to monitor the competition of copper(II) partition between kanamycin A
      and human serum albumin. We show, that the drug is able to digest Cu(II) ions
      from HSA to some extent and comparing the stability constants for metal and
      antibiotic with those, obtained for the N-terminal Asp-Ala-His-Lys (DAHK)
      sequence, which constitutes a copper(II) binding domain within albumin, we
      demonstrate that the Cu(II)-kanamycin A complex formation is possible also in
      blood plasma. Bioassays and immunoassay were used to find out the possibility of
      Cu(II)-kanamycin A complexes to induce cytokines: tumor necrosis factor (TNF),
      interferon (IFN) and interleukin-10 (IL-10) in human peripheral blood leukocytes.
      The effect on the cytokines release was dose and time dependent and the
      interdependence between IL-10 and TNF stimulation was found. We report that
      Cu(II)-aminoglycoside systems can act as moderate inducers of TNF-alpha, IFN
      alpha/beta and IL-10 released from human leukocytes. We have also found that
      these complexes are non-toxic for human A549 cells.

PMID- 14729306
TI  - Coordination features of difunctionalized beta-cyclodextrins with carnosine: ESI
      MS and spectroscopic investigations on 6A,6D-di-(beta-alanyl-L-histidine)-6A,6D
      dideoxy-beta-cyclodextrin and 6A,6C-di-(beta-alanyl-L-histidine)-6A,6C-dideoxy
      beta-cyclodextrin and their copper(II) complexes.
AB  - The synthesis and characterization of two beta-cyclodextrins (beta-CD)
      functionalized with two units of carnosine (beta-alanyl-L-histidine) through the
      amino group, 6A,6C-(beta-alanyl-L-histidine)-6A,6C-dideoxy-beta-cyclodextrin
      (ACCDAH) and 6A,6D-(beta-alanyl-L-histidine)-6A,6D-dideoxy-beta-cyclodextrin
      (ADCDAH), are reported. NMR and C.D. data of the ligands indicate a different
      interaction of dipeptide chains with upper rim and cavity of beta-CD.
      Analogously, spectroscopic and electrospray ionization mass spectrometry data
      show different copper(II) complex species formed by the two regioisomers. The
      ability of carnosine-cyclodextrin derivatives to bind copper ions in a head-to
      tail fashion induces the formation of oligomeric species (up to hexamers) in the
      case of ACCDAH, where the two carnosine moieties are adjacent, while in the
      ADCDAH case the mutual interaction between the peptidic chains of two ADCDAH
      molecules allows the almost exclusive formation of a copper-assisted self
      assembled dimeric species.

PMID- 14729307
TI  - Through metal binding, curcumin protects against lead- and cadmium-induced lipid
      peroxidation in rat brain homogenates and against lead-induced tissue damage in
      rat brain.
AB  - Curcumin, the major constituent of turmeric is a known, naturally occurring
      antioxidant. The present study examined the ability of this compound to protect
      against lead-induced damage to hippocampal cells of male Wistar rats, as well as
      lipid peroxidation induced by lead and cadmium in rat brain homogenate. The
      thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation
      induced by lead and cadmium in rat brain homogenate. The results show that
      curcumin significantly protects against lipid peroxidation induced by both these
      toxic metals. Coronal brain sections of rats injected intraperitoneally with lead
      acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were
      compared microscopically to determine the extent of lead-induced damage to the
      cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of
      curcumin to prevent such damage. Lead-induced damage to the neurons was
      significantly curtailed in the rats injected with curcumin. Possible chelation of
      lead and cadmium by curcumin as its mechanism of neuroprotection against such
      heavy metal insult to the brain was investigated using electrochemical,
      ultraviolet spectrophotometric and infrared spectroscopic analyses. The results
      of the study show that there is an interaction between curcumin and both cadmium
      and lead, with the possible formation of a complex between the metal and this
      ligand. These results imply that curcumin could be used therapeutically to
      chelate these toxic metals, thus potentially reducing their neurotoxicity and
      tissue damage.

PMID- 14729308
TI  - Two azurins with unusual redox and spectroscopic properties isolated from the
      Pseudomonas chlororaphis strains DSM 50083T and DSM 50135.
AB  - Two azurins (Az624 and Az626) were isolated from the soluble extract of two
      strains of Pseudomonas chlororaphis, DSM 50083(T) and DSM 50135, respectively,
      grown under microaerobic conditions with nitrate as final electron acceptor. The
      azurins, purified to electrophoretic homogeneity in three chromatographic steps,
      exhibit several peculiar properties. They have high reduction potentials and
      lower pI than most azurins described in the literature. As previously observed
      for Pseudomonas aeruginosa azurin, their reduction potentials are pH-dependent,
      but the pK values of their oxidized forms are lower, which suggests that deeper
      structural changes are associated with the oxidation process of these novel
      azurins. A hitherto undescribed pH-dependence of the diffusion coefficient was
      observed in Az624, that could be caused either by conformational changes, or by
      the formation of supramolecular aggregates associated with a protonation process.
      Both azurins exhibit axial X-band electron paramagnetic resonance spectra in
      frozen solution showing a typical hyperfine with the copper nucleus (I=3/2) and a
      well-resolved superhyperfine structure with two equivalent 14N nucleus (I=1),
      which is not usually observed for azurins from other species.

PMID- 14729309
TI  - Solution structure, enzymatic, and non-enzymatic reactivity of 3
      isoadenosylcobalamin, a structural isomer of coenzyme B12 with surprising
      coenzymic activity.
AB  - The coenzymic activity of eight analogs of coenzyme B(12) (5'-deoxyadenosyl
      cobalamin, AdoCbl) with structural alterations in the Ado ligand has been
      investigated with the AdoCbl-dependent ribonucleoside triphosphate reductase
      (RTPR) from Lactobacillus leichmannii. Six of the analogs were partially active
      coenzymes, and one, 3-iso-5'-deoxyadenosylcobalamin (3-IsoAdoCbl) was nearly as
      active as AdoCbl itself. NMR-restrained molecular modeling of 3-IsoAdoCbl
      revealed a highly conformationally mobile structure which required a four state
      model to be consistent with the NMR data. Thus, two conformations, one with the
      IsoAdo ligand over the eastern quadrant of the corrin, and one with the IsoAdo
      ligand over the northern quadrant, each undergo a facile syn/anti conformational
      equilibrium in the IsoAdo ligand. Spectrophotometric measurement of the kinetics
      of RTPR-induced cleavage of the carbon-cobalt bond of 3-IsoAdoCbl showed that it
      binds to the enzyme with the same affinity as AdoCbl, but its homolysis is only
      20% as rapid. Investigation of the non-enzymatic thermolysis of 3-IsoAdoCbl
      showed that like AdoCbl, 3-IsoAdoCbl decomposes by competing homolytic and
      heterolytic pathways. A complete temperature-dependent kinetic and product
      analysis, followed by correction for the base-off species permitted deconvolution
      of the specific rate constant for both pathways. Eyring plots for the homolysis
      and heterolysis rate constant cross at 93 degrees C, so that homolysis is the
      predominant pathway at high temperature, but heterolysis is the predominant
      pathway at low temperature. At 37 degrees C, the homolysis of 3-IsoAdoCbl is 5.5
      fold faster than that of AdoCbl, and the enzyme catalyzes carbon-cobalt bond
      homolysis in 3-IsoAdoCbl by a factor of 5.9 x 10(7), only 3.9% of the catalytic
      efficiency with AdoCbl itself. It seems likely that the conformational
      flexibility of 3-IsoAdoCbl allows it to adopt a coformation in which the hydrogen
      bonding patterns of the adenine moiety are similar to those of AdoCbl itself, and
      that this is responsible for the high enzymatic activity of this analog.

PMID- 14729310
TI  - Synthesis, characterization and biological activity of copper complexes with
      pyridoxal thiosemicarbazone derivatives. X-ray crystal structure of three dimeric
      complexes.
AB  - A dimeric copper complex of the unsubstituted pyridoxal thiosemicarbazone
      (H(2)L), [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O, previously tested on Friend murine
      cell lines has been recently resynthesized to evaluate its behavior on different
      murine and human leukemic cell lines and has been compared, in vitro and in vivo,
      with its monomeric counterpart [Cu(H(2)L)(OH(2))Cl]Cl. On TS/A murine
      adenocarcinoma cell line in vitro, both compounds significantly inhibit cell
      proliferation at micromolar concentrations, although the dimeric compound is more
      active. Despite this cytotoxicity they lack in vivo activity on TLX5 lymphoma.
      The unsubstituted dimeric [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O induces apoptosis on
      CEM and U937 human cell lines, with IC(50) concentrations of 1.2 x 10(-5) and 6.7
      x 10(-6) M, respectively, but it is inactive on K562. Moreover, it alters
      significantly the cell cycle of U937 and CEM lines and decreases the telomerase
      activity of U937. To verify if other dimeric copper complexes show relevant
      biological activity new complexes with N-substituted pyridoxal thiosemicarbazones
      have been synthesized and characterized using spectroscopic techniques. Three of
      them, namely [Cu(Me(2)-HL)Cl](2).6H(2)O (Me(2)-H(2)L=pyridoxal N1,N1
      dimethylthiosemicarbazone) (1), [Cu(MeMe-HL)Cl](2)Cl(2).4H(2)O (MeMe-HL=pyridoxal
      N1,N2-dimethylthiosemicarbazone) (2), [Cu(Et-H(2)L)Cl](2)Cl(2).2H(2)O (Et
      H(2)L=pyridoxal N1-ethylthiosemicarbazone) (3), were also characterized by X-ray
      diffractometry. These complexes are dimeric and all three present a square
      pyramidal coordinative geometry with the ligand showing an SNO tridentate
      behavior. Their biological activities have been tested in vitro on U937, CEM and
      K562 cell lines to ascertain their effectiveness in comparison to the
      corresponding unsubstituted complex [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O. Compound 1
      shows weak proliferation inhibition on all three cell lines, but it does not
      induce apoptosis and it does not inhibit telomerase activity, compound 2 is not
      effective at low concentration and is toxic at higher doses; compound 3 inhibits
      CEM cell growth better than complex 1 but it does not exert any other biological
      effect.

PMID- 14729311
TI  - Synthesis, characterization and biological activity of Ni, Cu and Zn complexes of
      isatin hydrazones.
AB  - Nickel, copper, and zinc complexes of isatin (H(2)L(1)) and N-methylisatin 3
      picolinoyl hydrazone (HL(2)), were synthesized and characterized by means of
      spectroscopic techniques. H(2)L(1) and a nickel complex [Ni(L(2))(2)].2C(6)H(14)
      were also characterized by X-ray diffractometry. Biological studies, carried out
      in vitro on human leukemic cell lines TOM 1 and NB4, have shown that both ligands
      and some copper and nickel complexes are active in inhibiting cell proliferation.
      Compounds H(2)L(1), Cu(HL(1))(2).2H(2)O, Zn(HL(1))(2).2H(2)O inhibit DNA
      synthesis and act constantly with time between 0 and 72 h. The cell cycle
      analysis has highlighted a reduction in the number of cells in phase S of about
      40%. The same compounds present only a precocious action on cell line NB4 and
      therefore their activity is cell target specific.

PMID- 14729312
TI  - Synthesis, X-ray crystal structure, antimicrobial activity and photodynamic
      effects of some thiabendazole complexes.
AB  - An interesting series of metal complexes of thiabendazole (tbz) is synthesized
      and characterized by elemental analyses and spectroscopic studies. The crystal
      structure of the hydrogen bonded one dimensional Co(II) complex, namely
      [Co(tbz)(2)(NO(3))(H(2)O)](NO(3)) is solved by single crystal X-ray diffraction.
      The complex crystallizes in monoclinic space group P2(1)/a with unit cell
      parameters, a=14.366(2), b=11.459(4), c=15.942(3) A, beta=113.78(3) degrees and
      z=4. The unit cell packing reveals an extensive hydrogen bonding involving a
      water molecule, nitrate ligands and the protonated nitrogen atoms of the tbz
      ligands, resulting in a one dimensional hydrogen bonding pattern. The
      antimicrobial activity of the complexes against selected bacteria (Escherichia
      coli and Bacillus subtilis) and yeast (Aspergillus flavues) is estimated. The
      relationship between the enzymatic production of ROS and antimicrobial activity
      of the complexes is examined, and a good correlation between two factors is
      found. Photodynamic quantum yields of singlet oxygen production (RNO bleaching
      assay) and rate of superoxide generation (SOD inhibitable ferricytochrome c
      reduction assay and EPR spin trapping experiments using 5,5-dimethyl-1-pyrroline
      N-oxide as spin trap) by the metal complexes have been studied.

PMID- 14729313
TI  - Characterization of oxovanadium (IV) complexes of D-gluconic and D-saccharic
      acids and their bioactivity on osteoblast-like cells in culture.
AB  - Oxovanadium (IV) complexes of the alpha-hydroxycarboxylic ligands D-gluconic and
      D-saccharic acids of stoichiometry Na(2)[VO(gluconate)(2)].H(2)O,
      K(2)[VO(saccharate)(2)].4H(2)O, Na(4)[VO(gluconate)(2)].2H(2)O and
      K(5)[VO(saccharate)(2)].4H(2)O were obtained in aqueous solutions; the first two
      in acid, the other two in alkaline media. They were characterized by infrared and
      UV-Vis spectroscopies, thermoanalytical (thermogravimetric and differential
      thermal analysis) data and magnetic susceptibility measurements. The complexes
      were found to be mononuclear, possessing the VO(2+) moiety, and the thorough
      analysis of the spectral data allowed the determination of the characteristics of
      the metal-to-ligand interactions. The biological activities of these complexes on
      the proliferation, differentiation and glucose consumption were tested on
      osteoblast-like cells in culture. Comparisons of these effects and those of the
      oxovanadium (IV) cation and the free ligands were performed. Different behaviors
      could be observed for the complexes obtained at acidic or alkaline pH-values, as
      well as for the different cellular types. The free ligands did not show any
      biological effect.

PMID- 14729314
TI  - Metal ion chelating peptoids with potential as anti-oxidants: complexation
      studies with cupric ions.
AB  - The cupric ion binding characteristics of the chelator EDTA bis (ethyl
      tyrosinate) are reported. Potentiometric studies in aqueous solutions over the pH
      range of 2.0-12.0 allowed identification and quantification of the species in
      solution. The principal species CuA predominates over the physiological pH range
      of 4.0-8.0 pH units. The logarithm of the stability constant (log beta(pqr)) for
      this species is 16.43. The cupric ion binding characteristics were further
      assessed using electronic absorption spectroscopic investigations. These results
      support the use of this chelator as a metal binding anti-oxidant.

PMID- 14729315
TI  - Kinetics and mechanism of the reduction of CrVI and CrV by D-lactobionic acid.
AB  - The oxidation of D-lactobionic acid by Cr(VI) yields the 2-ketoaldobionic acid
      and Cr(3+) as final products when a 20-times or higher excess of the aldobionic
      acid over Cr(VI) is used. The redox reaction takes place through a complex
      multistep mechanism, which involves the formation of intermediate Cr(IV) and
      Cr(V) species. Cr(IV) reacts with lactobionic acid much faster than Cr(V) and
      Cr(VI) do, and cannot be directly detected. However, the formation of CrO(2)(2+),
      observed by the first time for an acid saccharide/Cr(VI) system, provides
      indirect evidence for the intermediacy of Cr(IV) in the reaction path. Cr(VI) and
      the intermediate Cr(V) react with lactobionic acid at comparable rates, being the
      complete rate laws for the Cr(VI) and Cr(V) consumption expressed by: 
      d[Cr(VI)]/dt=[k(I)+k(II)[H(+)]][lactobionicacid][Cr(VI)], where k(I)=(4.1+/-0.1)
      x 10(-3) M(-1) s(-1) and k(II)=(2.1+/-0.1) x 10(-2) M(-2) s(-1); and 
      d[Cr(V)]/dt=[k(III)[H(+)]+(k(IV)+k(V)[H(+)])[lactobionicacid]] [Cr(V)], where
      k(III)=(1.8+/-0.1) x 10(-3) M(-1) s(-1), k(IV)=(1.1+/-0.1) x 10(-2) M(-1) s(-1)
      and k(V)=(1.0+/-0.1) x 10(-2) M(-2) s(-1), at 33 degrees C. The Electron
      Paramagnetic Resonance (EPR) spectra show that five-co-ordinate oxo-Cr(V)
      bischelates are formed at pH 1-5 with the aldobionic acid bound to Cr(V) through
      the alpha-hydroxyacid group.

PMID- 14729316
TI  - Binuclear copper(II) complexes of tolfenamic: synthesis, crystal structure,
      spectroscopy and superoxide dismutase activity.
AB  - The synthesis and characterization of copper(II) complexes with a potent non
      steroidal anti-inflammatory drug, tolfenamic acid, Htolf, with formula
      [Cu(tolf)(2)L](2) (where L is H(2)O or DMF, N,N-dimethylformamide) were
      investigated. The crystal and molecular structure of [Cu(tolf)(2)(DMF)](2) was
      reported. Crystallographic data are as follows: monoclinic system, space group
      P2(1)/n with cell constants a=9.068(2) A, b=14.514(3) A, c=22.826(4) A,
      V=2948.9(10) A(3) and Z=2. The crystal structure consists of binuclear, quadruply
      bridged neutral molecule with a Cu-Cu bond length of 2.6075(19) A. The complex is
      self-assembled via C-H-pi intermolecular stacking interactions. Spectroscopic and
      electrochemical studies were reported. The superoxide dismutase activity is
      measured and compared with those of superoxide dismutase enzyme, SOD, the free
      ligand and related copper complexes with non-steroidal anti-inflammatory drugs,
      NSAIDs. IC(50) value was measured by the Fridovich test (1.97+/-0.17 microM),
      which showed that [Cu(tolf)(2)L](2) is a good superoxide scavenger.

PMID- 14729317
TI  - Fluorescent assay for riboflavin binding to cytochrome P450 2B4.
AB  - The interactions between the hemoprotein cytochrome P450 2B4 (CYP 2B4) and
      riboflavin - a low molecular weight component of the flavoprotein NADPH-dependent
      cytochrome P450 reductase - were investigated by fluorescence spectroscopy.
      Riboflavin fluorescence quenching by cytochrome P450 2B4 was used to probe the
      ligand-enzyme binding (lambda(ex)=385 nm, lambda(em)=520 nm). Fluorescence
      titration experiments showed formation of a complex between cytochrome P450 2B4
      and riboflavin with an apparent dissociation constant value, K(d)=8.8+/-1 microM.
      The fluorescence intensity of riboflavin was decreased with increasing the
      cytochrome P450 2B4 concentration, indicating the transfer of resonance
      excitation energy from riboflavin (energy donor) to the cytochrome P450 2B4 heme
      (energy acceptor). The data obtained are suggestive of the existence of
      riboflavin binding site(s) on the hemeprotein molecule.

PMID- 14729318
TI  - EPR study of the dynamic behavior of cis,cis-1,3,5-triaminocyclohexane Cu(II)
      complex on B-form DNA-fibers.
AB  - The orientation and the dynamic behavior of [Cu(TACH)](2+)(TACH = cis,cis-1,3,5
      triaminocyclohexane) on B-form DNA-fiber have been investigated by electron
      paramagnetic resonance (EPR) spectroscopy. The complex showed novel EPR spectra
      indicating that a rapidly moving species (X) is in equilibrium with a
      stereospecifically oriented species (Y) on the DNA-fiber in the range 20 and -20
      degrees C. The thermodynamic parameters Delta H and Delta S of the equilibrium X
      right arrow over left arrow Y are respectively -51.3 kJmol(-1) and -1.9 x 10(2)
      JK(-1)mol(-1) for the DNA-fibers prepared at pH 7 and -47.1 kJmol(-1) and -1.7 x
      10(2) JK(-1)mol(-1) for the DNA-fibers prepared at pH 9. These results suggest
      that the equilibrium involved a concerted structural change of the coordination
      sphere and the hydrogen bonding network around the complex on the B-form DNA
      fibers. The orientation of the species Y was completely randomized below -20
      degrees C, indicating that the freezing of the water molecules in the DNA-fibers
      breaks down the hydrogen bonding network which regulated the orientation of the
      complex in the DNA-fibers. The correlation between the observed dynamic behavior
      and the hydrolytic ability of the complex was also discussed.

PMID- 14729319
TI  - Metal-assisted light-induced DNA cleavage activity of 2
      (methylthio)phenylsalicylaldimine Schiff base copper(II) complexes having planar
      heterocyclic bases.
AB  - Ternary copper(II) complexes [CuLL'](ClO(4)), where HL is NSO-donor Schiff base
      (2-(methylthio)phenyl)salicylaldimine and L' is NN-donor phenanthroline bases
      like 1,10-phenanthroline (phen), dipyridoquinoxaline (dpq) and 2,9-dimethyl-1,10
      phenanthroline (dmp), are prepared and structurally characterized by X-ray
      crystallography. The complexes have a distorted square-pyramidal (4+1) CuN(3)OS
      coordination geometry. While [CuL(phen)](ClO(4)) and [CuL(dpq)](ClO(4)) show
      axial sulfur ligation, [CuL(dmp)](ClO(4)) has the sulfur bonded at the equatorial
      site. The one-electron paramagnetic complexes exhibit axial electron paramagnetic
      resonance (EPR) spectra in dimethylformamide glass at 77 K. The complexes are
      redox active and a quasireversible electron transfer process near 0.0 V vs
      saturated calomel electrode (SCE) in DMF-Tris buffer (1:4 v/v at pH 7.2)
      involving Cu(II)/Cu(I) couple is observed for the phen and dpq complexes. The dmp
      complex exhibits an irreversible reduction process forming bis(dmp)copper(I)
      species. A profound effect of the substituents of the phenanthroline bases is
      observed on the binding of the complexes to the calf thymus (CT) and in the
      cleavage of supercoiled (SC) pUC19 DNA. The phen and dpq complexes show DNA
      cleavage activity in presence of mercaptopropionic acid (MPA). The dmp complex is
      cleavage inactive in presence of MPA. All the complexes show photocleavage
      activity when irradiated with a monochromatic UV light of 312 nm. The dpq complex
      also cleaves SC DNA on visible light irradiation at 436, 532 and 632.8 nm but
      with a longer exposure time and higher complex concentration. The cleavage
      reactions in presence of MPA are found to involve hydroxyl radical. The
      photocleavage reactions are found to occur under aerobic conditions showing an
      enhancement of cleavage in D(2)O and inhibition with azide addition suggesting
      formation of singlet oxygen as a reactive species. The roles of sulfur of the
      Schiff base as photosensitizer and the phenanthroline bases as minor groove
      binder, and their influence on the photocleavage activity are discussed. The
      quinoxaline ligand exhibits significant photosensitizing effect assisted by the
      copper(II) center.

PMID- 14729320
TI  - A Schiff base complex of chromium(III): an efficient inhibitor for the pathogenic
      and invasive potential of Shigella dysenteriae.
AB  - A Schiff base complex of chromium(III), transdiaqua[N,N'ethylenebis
      (salicylideneimine)chromium(III)]perchlorate, [Cr(salen)(OH(2))(2)](+), was found
      to have an inhibitory effect on the growth of Shigella dysenteriae. The
      chromium(III) complex was found to cure (remove) the invasive plasmid and thereby
      render the microbe more sensitive to the tested antibiotics. The loss in the
      catalytic activity of the isolated endo-alpha-N-acetyl galactosaminidase on mucin
      as a substrate was also observed in the presence of [Cr(salen)(OH(2))(2)](+).
      This suggests that [Cr(salen)(OH(2))(2)](+) is toxic to the microbe and could
      make the microbe non-pathogenic and non-invasive, thus establishing its role in
      microbiological applications to reduce the toxic potentials of a microbe.

PMID- 14729321
TI  - Solution, solid state and biological characterization of ruthenium(III)-DMSO
      complexes with purine base derivatives.
AB  - Two new complexes of Ru(III) with purine base derivatives, [mer-RuCl(3)(acv)(DMSO
      S)(C(2)H(5)OH)].C(2)H(5)OH (1) (acv=acyclovir, DMSO=dimethyl sulfoxide) and
      [trans-RuCl(4)(guaH)(DMSO-S)].2H(2)O (2) (guaH=protonated molecule of guanine),
      were prepared from the same Ru(III) precursor, [trans-RuCl(4)(DMSO-S)(2)](-), by
      substitution of one DMSO-S. Coordination of acv induced also replacement of one
      chloride by an ethanol molecule. This reactivity difference was explained by
      striking contrasts in the hydrogen bonding schemes of the two complexes,
      evidenced in their X-ray crystal structures. In 1 the guanine derivative
      acyclovir is coordinated to ruthenium through the N(7) atom, while in 2 the
      protonated guanine molecule is bound through the N(9) atom. Both complexes were
      also characterized by various physico-chemical methods in the solid state and in
      the solution. In vitro, the biological activity of 2 and of the previously
      described complexes [mer-RuCl(3)(acv)(DMSO-S)(CH(3)OH)].0.5CH(3)OH (3) and [mer
      RuCl(3)(acv)(DMSO-S)(H(2)O)].H(2)O (4) on tumour cells appear to be very similar
      to that of NAMI-A (NAMI-A=[ImH][trans-RuCl(4)(DMSO-S)Im]). All compounds are only
      weakly active on tumour cell proliferation but show an interesting proadhesive
      effect that suggest possible activity on tumour malignancy.

PMID- 14729322
TI  - The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA
      binding and antimetastatic activity: an NMR evaluation.
AB  - The coordination of the antimetastatic agent NAMI-A, [H(2)im][trans-RuCl(4)(dmso
      S)(Him)], (Him=imidazole; dmso=dimethyl sulfoxide), to the DNA model base 9
      methyladenine (9-MeAde) was investigated in water. NMR spectroscopy was first
      applied for the study of the molecular stability and hydrolysis of NAMI-A in
      aqueous solution over a range of pH (3.0-7.4) and chloride ion concentrations (0
      1 M) at 37.0 degrees C. In physiological conditions (phosphate buffer, pH 7.4)
      NAMI-A disappears from the solution in 15 min due to chloride and dmso
      hydrolysis, leading to uncharacterised poly-oxo Ru species. Conversely, at lower
      pH (3.0-6.0) and in water (pH approximately 5.5), only a partial dmso hydrolysis
      occurs, slowly forming the [trans-RuCl(4)(H(2)O)(Him)](-) complex. This latter
      species coordinates to 9-MeAde (via the N7 of 9-MeAde), forming the [trans
      RuCl(4)(9-MeAde)(Him)](-) complex. NAMI-A and [trans-RuCl(4)(H(2)O)(Him)](-) give
      comparable intracellular ruthenium concentrations and accumulate in KB cells
      (human mouth carcinoma) and accumulate these at the G(2)/M phase, while poly-oxo
      Ru species do not, and their cell uptake is reduced to 50%. On the contrary,
      G(2)/M arrest and protein content in the murine metastatic cell line metGM, are
      not influenced by NAMI-A hydrolysis. Hydrolysed NAMI-A species apparently are
      easier taken up by the metGM cells, showing intracellular ruthenium
      concentrations one order of magnitude greater than those of intact NAMI-A.
      Therefore, it is proposed that the selective antimetastatic activity of NAMI-A
      during in vivo experiments can be attributed to its hydrolysed species.

PMID- 14729323
TI  - Model complexes with naturally occurring ligands (salicylglycine and imidazol)
      and the biometals copper and cobalt.
AB  - Two new complexes [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl] (2)(2-OH-Hip)(2) (1) and [Co(2
      OH-Hip)(Imz)(3)].H(2)O (2) (with Imz=Imidazol and 2-OH-Hip=2-hydroxyhippuric
      acid) were prepared and characterized. The molecular structures and the solution
      and solid state behavior of the complexes were investigated. Complex 1
      crystallizes in the monoclinic space group P2(1)/c with a=16.880(1), b=8.046(1),
      c=24.683(1) A, beta=107.88(1) degrees, and Z=2, while complex 2 crystallizes in
      the orthorhombic space group Pbca with a=11.712(2), b=15.741(4), c=22.254(4) A,
      and Z=8. The [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl](2)(2-OH-Hip)(2) solid consists in
      two distinct monomeric Cu(II) complexes: one of them is neutral octahedral
      [Cu(Imz)(4)Cl(2)] and the other, charged square basis pyramida [Cu(Imz)(4)Cl](+).
      The 2-hydroxyhippuric acid, which here acts as a counter ion, is deprotonated at
      its carboxylic group. Cobalt(III) ion in [Co(2-OH-Hip)(Imz)(3)].H(2)O is at the
      center of an octahedral environment, coordinated to three Imidazol ligands and to
      a triply deprotonated 2-hydroxyhippuric acid molecule acting as a tridentate
      ligand. Aqueous solution equilibrium of the quaternary system Cu(2+)/2-OH
      Hip/Imz/H(+) was studied by potentiometric titrations.

PMID- 14729324
TI  - The small Tim proteins and the twin Cx3C motif.
AB  - The mitochondrial intermembrane space contains the 'small' Tim (translocase of
      inner membrane) proteins that are marked by their conserved 'twin Cx(3)C' motif
      separated by 11-16 residues. Together with the Tim22 complex at the inner
      membrane, the small Tim proteins form the TIM22 import machinery that mediates
      the biogenesis of polytopic inner membrane proteins. Upon first investigation,
      the conserved motif resembles a zinc-finger-like domain, but the spacing between
      the cysteine residues differs from that a canonical zinc finger. Recent
      publications present different views about the function of the conserved
      cysteines: the cysteines form a zinc-finger-like structure to coordinate zinc or,
      alternatively, they form juxtapositioned disulfide bonds.

PMID- 14729325
TI  - HTTM, a horizontally transferred transmembrane domain.
AB  - Sequence analysis of vitamin K-dependent gamma-carboxylases (VKGC) has revealed
      the presence of a novel domain, HTTM (for horizontally transferred transmembrane)
      in its N terminus. In contrast to most known domains, HTTM contains four
      transmembrane regions. Its occurrence in eukaryotes, bacteria and archaea is
      probably caused by horizontal gene transfer rather than by early evolution. The
      conservation of VKGC catalytic sites also indicates an enzymatic function for the
      other family members.

PMID- 14729326
TI  - Resuscitation-promoting factors possess a lysozyme-like domain.
AB  - The novel bacterial cytokine family--resuscitation-promoting factors (Rpfs)-
      share a conserved domain of uncharacterized function. Predicting the structure of
      this domain suggests that Rpfs possess a lysozyme-like domain. The model
      highlights the good conservation of residues involved in catalysis and substrate
      binding. A lysozyme-like function makes sense for this domain in the light of
      experimental characterization of the biological function of Rpfs.

PMID- 14729327
TI  - The riboswitch control of bacterial metabolism.
AB  - Aptamers are artificial nucleic acids that selectively bind small molecules. In
      the past two years, it has become clear that nature has already devised its own
      aptamers that play important regulatory roles. RNA sensors have been discovered
      in both Gram-positive and Gram-negative bacteria that function as molecular
      switches in response to direct binding of structurally diverse metabolites. These
      natural RNA aptamers, called 'riboswitches', are imbedded in the leader sequences
      of numerous metabolic genes. Riboswitches are able to repress or activate their
      cognate genes at both transcriptional and translational levels. Here, we
      summarize the recent progress in the identification and characterization of
      riboswitches and discuss their evolution and distribution.

PMID- 14729328
TI  - The AMP-activated protein kinase cascade--a unifying system for energy control.
AB  - AMP-activated protein kinase (AMPK) is the downstream component of a protein
      kinase cascade that acts as an intracellular energy sensor maintaining the energy
      balance within the cell. This pivotal role of AMPK places it in an ideal position
      for regulating whole-body energy metabolism, and AMPK might play a part in
      protecting the body from metabolic diseases such as type 2 diabetes and obesity.
      Mutations in AMPK cause cardiac hypertrophy and arrhythmia. Recent findings have
      identified LKB1--a protein kinase that is mutated in a hereditary form of cancer-
      as a candidate for the upstream kinase in the AMPK cascade. AMPK could provide a
      link in human diseases of which the underlying cause is due to defects in energy
      metabolism.

PMID- 14729329
TI  - Translation factors: in sickness and in health.
AB  - It has been known for many years that aberrant levels of the factors involved in
      translation of mRNA can contribute to disease, most notably cancer. However,
      despite the wealth of information gathered about initiation and elongation
      factors from biochemical studies in mammalian cells, and from mutation analysis
      in lower organisms, little was known until recently about the effects that
      mutations in these factors could have on cellular function in higher organisms.
      In the past few years, this balance has started to be redressed, and we are at a
      fascinating stage in the molecular pathology of translation factors. It has been
      discovered recently that mutations in subunits of eukaryotic initiation factor 2B
      (eIF2B) underlie the neurodegenerative disease termed 'vanishing white matter'.

PMID- 14729330
TI  - TSC2: filling the GAP in the mTOR signaling pathway.
AB  - The tumor-suppressor proteins TSC1 and TSC2 are associated with an autosomal
      dominant disorder known as tuberous sclerosis complex (TSC). TSC1 and TSC2
      function as a heterodimer to inhibit cell growth and proliferation. Another
      protein, mTOR (mammalian target of rapamycin), is regarded as a central
      controller of cell growth in response to growth factors, cellular energy and
      nutrient levels. Recent breakthroughs in TSC research link the TSC1/2 heterodimer
      protein to the mTOR signaling network. It has recently been shown that TSC2 has
      GTPase-activating protein (GAP) activity towards the Ras family small GTPase Rheb
      (Ras homolog enriched in brain), and TSC1/2 antagonizes the mTOR signaling
      pathway via stimulation of GTP hydrolysis of Rheb. Thus, TSC1/2 and Rheb have
      pivotal roles in mediating growth factors, nutrient and energy sensing signals to
      mTOR-dependent targets. These discoveries lend new insight into TSC pathogenesis.

PMID- 14729331
TI  - Cytoplasmic gatekeepers of K+-channel flux: a structural perspective.
AB  - Recently, rapid progress in our structural knowledge of K(+)-selective channels
      has started to provide a basis for comprehending the biophysical machinery
      underlying their electrophysiological properties. These studies have begun to
      reveal how a diverse array of distinct, cytoplasmically positioned domains affect
      the activity of associated channels. Some of these establish functional diversity
      by selectively mediating channel assembly. More importantly, these cytoplasmic
      domains couple intracellular signals to the gating of their associated pore. New
      structural insights are providing a clearer understanding of the fundamental
      molecular mechanisms of these K(+) channels that, in turn, partly underlie
      complex neurological phenomena.

PMID- 14729332
TI  - Historical review: Deciphering the genetic code--a personal account.
AB  - This is an autobiographical description of the events that led to the breaking of
      the genetic code and the subsequent race to decipher the code. The code was
      deciphered in two stages over a five-year period between 1961 and 1966. During
      the first stage, the base compositions of codons were deciphered by the directing
      cell-free protein synthesis with randomly ordered RNA preparations. During the
      second phase, the nucleotide sequences of RNA codons were deciphered by
      determining the species of aminoacyl-tRNA that bound to ribosomes in response to
      trinucleotides of known sequence. Views on general topics such as how to pick a
      research problem and competition versus collaboration also are discussed.

PMID- 14729333
TI  - Heparin binds to the laminin alpha4 chain LG4 domain at a site different from
      that found for other laminins.
AB  - We previously reported that the LG4 domain of the laminin alpha4 chain is
      responsible for high-affinity heparin binding. To specify the amino acid residues
      involved in this activity, we produced a series of alpha4 LG4-fusion proteins in
      which each of the 27 basic residues (arginine, R; histidine; lysine, K) were
      replaced one by one with alanine (A). When the effective residues R1520A, K1531A,
      K1533A, and K1539A are mapped on a structural model, they form a track on the
      concave surface of the beta-sandwich, suggesting that they interact with adjacent
      sulfate groups along the heparin chain. Whereas low-affinity heparin-binding
      sites of other LG domains have been located at the top of the beta-sheet sandwich
      opposite the N and C termini, the residues for high-affinity heparin binding of
      alpha4 LG4 reveal a new topological area of the LG module.

PMID- 14729334
TI  - Genomic analysis of bacteriophages SP6 and K1-5, an estranged subgroup of the T7
      supergroup.
AB  - We have determined the genome sequences of two closely related lytic
      bacteriophages, SP6 and K1-5, which infect Salmonella typhimurium LT2 and
      Escherichia coli serotypes K1 and K5, respectively. The genome organization of
      these phages is almost identical with the notable exception of the tail fiber
      genes that confer the different host specificities. The two phages have diverged
      extensively at the nucleotide level but they are still more closely related to
      each other than either is to any other phage currently characterized. The SP6 and
      K1-5 genomes contain, respectively, 43,769 bp and 44,385 bp, with 174 bp and 234
      bp direct terminal repeats. About half of the 105 putative open reading frames in
      the two genomes combined show no significant similarity to database proteins with
      a known or predicted function that is obviously beneficial for growth of a
      bacteriophage. The overall genome organization of SP6 and K1-5 is comparable to
      that of the T7 group of phages, although the specific order of genes coding for
      DNA metabolism functions has not been conserved. Low levels of nucleotide
      similarity between genomes in the T7 and SP6 groups suggest that they diverged a
      long time ago but, on the basis of this conservation of genome organization, they
      are expected to have retained similar developmental strategies.

PMID- 14729335
TI  - Ribosomal protein-dependent orientation of the 16 S rRNA environment of S15.
AB  - Ribosomal protein S15 binds specifically to the central domain of 16 S ribosomal
      RNA (16 S rRNA) and directs the assembly of four additional proteins to this
      domain. The central domain of 16 S rRNA along with these five proteins form the
      platform of the 30 S subunit. Previously, directed hydroxyl radical probing from
      Fe(II)-S15 in small ribonucleoprotein complexes was used to study assembly of the
      central domain of 16 S rRNA. Here, this same approach was used to understand the
      16 S rRNA environment of Fe(II)-S15 in 30 S subunits and to determine the
      ribosomal proteins that are involved in forming the mature S15-16 S rRNA
      environment. We have identified additional sites of Fe(II)-S15-directed cleavage
      in 30S subunits compared to the binary complex of Fe(II)-S15/16 S rRNA. Along
      with novel targets in the central domain, sites within the 5' and 3' minor
      domains are also cleaved. This suggests that during the course of 30S subunit
      assembly these elements are positioned in the vicinity of S15. Besides the
      previously determined role for S8, roles for S5, S6+S18, and S16 in altering the
      16 S rRNA environment of S15 were established. These studies reveal that
      ribosomal proteins can alter the assembly of regions of the 30 S subunit from a
      considerable distance and influence the overall conformation of this
      ribonucleoprotein particle.

PMID- 14729336
TI  - Structural and biochemical analysis of sliding clamp/ligand interactions suggest
      a competition between replicative and translesion DNA polymerases.
AB  - Most DNA polymerases interact with their cognate processive replication factor
      through a small peptide, this interaction being absolutely required for their
      function in vivo. We have solved the crystal structure of a complex between the
      beta sliding clamp of Escherichia coli and the 16 residue C-terminal peptide of
      Pol IV (P16). The seven C-terminal residues bind to a pocket located at the
      surface of one beta monomer. This region was previously identified as the binding
      site of another beta clamp binding protein, the delta subunit of the gamma
      complex. We show that peptide P16 competitively prevents beta-clamp-mediated
      stimulation of both Pol IV and alpha subunit DNA polymerase activities,
      suggesting that the site of interaction of the alpha subunit with beta is
      identical with, or overlaps that of Pol IV. This common binding site for delta,
      Pol IV and alpha subunit is shown to be formed by residues that are highly
      conserved among many bacterial beta homologs, thus defining an evolutionarily
      conserved hydrophobic crevice for sliding clamp ligands and a new target for
      antibiotic drug design.

PMID- 14729337
TI  - Redefinition of the cleavage sites of DNase I on the nucleosome core particle.
AB  - DNase I has been widely used for the footprinting of DNA-protein interactions
      including analyses of nucleosome core particle (NCP) structure. Our understanding
      of the relationship between the footprint and the structure of the nucleosome
      complex comes mainly from digestion studies of NCPs, since they have a well
      defined quasi-symmetrical structure and have been widely investigated. However,
      several recent results suggest that the established consensus of opinion
      regarding the mode of digestion of NCPs by DNase I may be based on erroneous
      interpretation of results concerning the relationship between the NCP ends and
      the dyad axis. Here, we have used reconstituted NCPs with defined ends, bulk NCPs
      prepared with micrococcal nuclease and molecular modelling to reassess the mode
      of DNase I digestion. Our results indicate that DNase I cuts the two strands of
      the nucleosomal DNA independently with an average stagger of 4 nt with the 3'
      ends protruding. The previously accepted value of 2 nt stagger is explained by
      the finding that micrococcal nuclease produces NCPs not with flush ends, but with
      approximately 1 nt 5'-recessed ends. Furthermore we explain why the DNA stagger
      is an even and not an odd number of nucleotides. These results are important for
      studies using DNase I to probe nucleosome structure in complex with other
      proteins or any DNA-protein complex containing B-form DNA. We also determine the
      origin of the 10n +/- 5 nt periodicity found in the internucleosomal ladder of
      DNase I digests of chromatin from various species. The explanation of the 10n +/-
      5 nt ladder may have implications for the structure of the 30 nm fibre.

PMID- 14729338
TI  - DNA sequence bias during Tn5 transposition.
AB  - Transposition is one of the primary mechanisms causing genome instability. This
      phenomenon is mechanistically related to other DNA rearrangements such as V(D)J
      recombination and retroviral DNA integration. In the Tn5 system, only one
      protein, the transposase (Tnp), is required for all of the catalytic steps
      involved in transposon movement. The complexity involved in moving multiple DNA
      strands within one active site suggests that, in addition to the specific
      contacts maintained between Tnp and its recognition sequence, Tnp also interacts
      with the flanking DNA sequence. Here, we demonstrate that Tnp interacts with the
      donor DNA region. Tnp protects the donor DNA from DNase I digestion, suggesting
      that Tnp is in contact with, or otherwise distorts, the donor DNA during
      synapsis. In addition, changes in the donor DNA sequence within this region alter
      the affinity of Tnp for DNA by eightfold during synapsis. In vitro selection for
      more stable synaptic complexes reveals an A/T sequence bias for this region. We
      further show that certain donor DNA sequences, which favor synapsis, also appear
      to serve as hot spots for strand transfer. The TTATA donor sequence represents
      the best site. Most surprising is the fact that this sequence is found within the
      Tnp recognition sequence. Preference for insertion into a site within the Tnp
      recognition sequence would effectively inactivate one copy of the element and
      form clusters of the Tn5 transposon. In addition, the fact that several donor DNA
      sequences, which favor synapsis, appear to serve as hot spots for transposon
      insertion suggest that similar criteria may exist for Tnp-donor DNA and Tnp
      target DNA interactions.

PMID- 14729339
TI  - Structural basis of oligomannose recognition by the Pterocarpus angolensis seed
      lectin.
AB  - The crystal structure of a Man/Glc-specific lectin from the seeds of the
      bloodwood tree (Pterocarpus angolensis), a leguminous plant from central Africa,
      has been determined in complex with mannose and five manno-oligosaccharides. The
      lectin contains a classical mannose-specificity loop, but its metal-binding loop
      resembles that of lectins of unrelated specificity from Ulex europaeus and
      Maackia amurensis. As a consequence, the interactions with mannose in the primary
      binding site are conserved, but details of carbohydrate-binding outside the
      primary binding site differ from those seen in the equivalent carbohydrate
      complexes of concanavalin A. These observations explain the differences in their
      respective fine specificity profiles for oligomannoses. While Man(alpha1-3)Man
      and Man(alpha1-3)[Man(alpha1-6)]Man bind to PAL in low-energy conformations
      identical with that of ConA, Man(alpha1-6)Man is required to adopt a different
      conformation. Man(alpha1-2)Man can bind only in a single binding mode, in sharp
      contrast to ConA, which creates a higher affinity for this disaccharide by
      allowing two binding modes.

PMID- 14729340
TI  - Assessing the flexibility of intermediate filaments by atomic force microscopy.
AB  - Eukaryotic cells contain three cytoskeletal filament systems that exhibit very
      distinct assembly properties, supramolecular architectures, dynamic behaviour and
      mechanical properties. Microtubules and microfilaments are relatively stiff polar
      structures whose assembly is modulated by the state of hydrolysis of the bound
      nucleotide. In contrast, intermediate filaments (IFs) are more flexible apolar
      structures assembled from a approximately 45 nm long coiled-coil dimer as the
      elementary building block. The differences in flexibility that exist among the
      three filament systems have been described qualitatively by comparing electron
      micrographs of negatively stained dehydrated filaments and by directly measuring
      the persistence length of F-actin filaments (approximately 3-10 microm) and
      microtubules (approximately 1-8 mm) by various physical methods. However,
      quantitative data on the persistence length of IFs are still missing. Toward this
      goal, we have carried out atomic force microscopy (AFM) in physiological buffer
      to characterise the morphology of individual vimentin IFs adsorbed to different
      solid supports. In addition, we compared these images with those obtained by
      transmission electron microscopy (TEM) of negatively stained dehydrated
      filaments. For each support, we could accurately measure the apparent persistence
      length of the filaments, yielding values ranging between 0.3 microm and 1 microm.
      Making simple assumptions concerning the adsorption mechanism, we could estimate
      the persistence length of an IF in a dilute solution to be approximately 1
      microm, indicating that the lower measured values reflect constraints induced by
      the adsorption process of the filaments on the corresponding support. Based on
      our knowledge of the structural organisation and mechanical properties of IFs, we
      reason that the lower persistence length of IFs compared to that of F-actin
      filaments is caused by the presence of flexible linker regions within the coiled
      coil dimer and by postulating the occurrence of axial slipping between dimers
      within IFs.

PMID- 14729341
TI  - Crystal structure of fully ligated adenylosuccinate synthetase from Plasmodium
      falciparum.
AB  - In the absence of the de novo purine nucleotide biosynthetic pathway in parasitic
      protozoa, purine salvage is of primary importance for parasite survival. Enzymes
      of the salvage pathway are, therefore, good targets for anti-parasitic drugs.
      Adenylosuccinate synthetase (AdSS), catalysing the first committed step in the
      synthesis of AMP from IMP, is a potential target for anti-protozoal chemotherapy.
      We report here the crystal structure of adenylosuccinate synthetase from the
      malaria parasite, Plasmodium falciparum, complexed to 6-phosphoryl IMP, GDP, Mg2+
      and the aspartate analogue, hadacidin at 2 A resolution. The overall architecture
      of P. falciparum AdSS (PfAdSS) is similar to the known structures from
      Escherichia coli, mouse and plants. Differences in substrate interactions seen in
      this structure provide a plausible explanation for the kinetic differences
      between PfAdSS and the enzyme from other species. Additional hydrogen bonding
      interactions of the protein with GDP may account for the ordered binding of
      substrates to the enzyme. The dimer interface of PfAdSS is also different, with a
      pronounced excess of positively charged residues. Differences highlighted here
      provide a basis for the design of species-specific inhibitors of the enzyme.

PMID- 14729342
TI  - Crystal structures of the group II chaperonin from Thermococcus strain KS-1:
      steric hindrance by the substituted amino acid, and inter-subunit rearrangement
      between two crystal forms.
AB  - The crystal structures of the group II chaperonins consisting of the alpha
      subunit with amino acid substitutions of G65C and/or I125T from the
      hyperthermophilic archaeum Thermococcus strain KS-1 were determined. These
      mutants have been shown to be active in ATP hydrolysis but inactive in protein
      folding. The structures were shown to be double-ring hexadecamers in an extremely
      closed form, which was consistent with the crystal structure of native
      alpha8beta8-chaperonin from Thermoplasma acidophilum. Comparisons of the present
      structures with the atomic structures of the GroEL14-GroES7-(ADP)7 complex
      revealed that the deficiency in protein-folding activity with the G65C amino acid
      substitution is caused by the steric hindrance of the local conformational change
      in an equatorial domain. We concluded that this mutant chaperonin with G65C
      substitution is deprived of the smooth conformational change in the refolding
      reaction cycle. We obtained a new form of crystal with a distinct space group at
      a lower concentration of sulfate ion in the presence of nucleotide. The crystal
      structure obtained at the lower concentration of sulfate ion tilts outward, and
      has much looser inter-subunit contacts compared with those in the presence of a
      higher concentration of sulfate ion. Such subunit rotation has never been
      characterized in group II chaperonins. The crystal structure obtained at the
      lower concentration of sulfate ion tilts outward, and has much looser inter
      subunit contacts compared with those in the presence of a higher concentration of
      sulfate ion.

PMID- 14729343
TI  - Structural characterisation of islet amyloid polypeptide fibrils.
AB  - Islet amyloid is found in many patients suffering from type 2 diabetes. Amyloid
      fibrils found deposited in the pancreatic islets are composed of a 37-residue
      peptide, known as islet amyloid polypeptide (IAPP) (also known as amylin) and are
      similar to those found in other amyloid diseases. Synthetic IAPP peptide readily
      forms amyloid fibrils in vitro and this has allowed fibril formation kinetics and
      the overall morphology of IAPP amyloid to be studied. Here, we use X-ray fibre
      diffraction, electron microscopy and cryo-electron microscopy to examine the
      molecular structure of IAPP amyloid fibrils. X-ray diffraction from aligned
      synthetic amyloid fibrils gave a highly oriented diffraction pattern with layer
      lines spaced 4.7 A apart. Electron diffraction also revealed the characteristic
      4.7 A meridional signal and the position of the reflection could be compared
      directly to the image of the diffracting unit. Cryo-electron microscopy revealed
      the strong signal at 4.7 A that has been previously visualised from a single
      Abeta fibre. Together, these data build up a picture of how the IAPP fibril is
      held together by hydrogen bonded beta-sheet structure and contribute to the
      understanding of the generic structure of amyloid fibrils.

PMID- 14729344
TI  - Structure formation in the C terminus of type III collagen guides disulfide cross
      linking.
AB  - In type III collagen the main triple-helical domain is followed by a disulfide
      knot and the C-terminal propeptide, which are both essential for nucleation,
      stabilization and registration of the triple helix. We demonstrate that oxidative
      inter-chain disulfide bridging does not occur between the knot sequences
      GlyProCysCysGly of dissociated randomly coiled chains. N-terminal fusion of the
      obligatory trimeric domain of mini-fibritin is able to direct this process
      efficiently, demonstrating a folded precursor mechanism in which the thiol groups
      have to be properly placed for the formation of native disulfide bonds. The
      natural C-propeptide domain may act in a similar way as the mini-fibritin domain.
      After disulfide linkage and triple-helix formation the catalyzing mini-fibritin
      domain was removed by thrombin cleavage. In this way a short but stable triple
      helical collagen fragment was expressed in Escherichia coli for structural and
      functional studies.

PMID- 14729345
TI  - Insights into conformation and dynamics of protein GB1 during folding and
      unfolding by NMR.
AB  - Understanding protein stability requires characterization of structural
      determinants of the folded and unfolded states. Many proteins are capable of
      populating partially folded states under specific solution conditions.
      Occasionally, coexistence of the folded and an unfolded state under non- or
      mildly denaturing conditions can be observed by NMR, allowing us to structurally
      probe these states under identical conditions. Here we report on a destabilized
      mutant of the B1 domain of protein G (GB1) whose equilibrium unfolding was
      systematically investigated. Backbone amide residual dipolar couplings (RDCs),
      the tryptophan Nepsilon-H resonance and the amide nitrogen transverse relaxation
      rates (R2s) for varying pH values and different temperatures were measured. The
      backbone amide RDCs indicate that prior to complete unfolding, two melting hot
      spots are formed at the turn around T11, L12 and K13 and the N terminus of the
      helix at A24 and T25. The RDCs for the low pH, thermally unfolded state of GB1
      are very small and do not indicate the presence of any native-like structure.
      Amide nitrogen transverse relaxation rates for GB1 in the folded state at
      different temperatures exhibit large contributions from exchange processes and
      the associated dynamics display considerable heterogeneity. Our data provide
      clear evidence for intermediate conformations and multi-state equilibrium
      un/folding for this GB1 variant.

PMID- 14729346
TI  - Rapid collapse precedes the fast two-state folding of the cold shock protein.
AB  - The cold shock protein Bc-Csp folds very rapidly in a reaction that is well
      described by a kinetic two-state mechanism without intermediates. We measured the
      shortening of six intra-protein distances during folding by Forster resonance
      energy transfer (FRET) in combination with stopped-flow experiments. Single
      tryptophan residues were engineered into the protein as the donors, and single 5
      (((acetylamino)ethyl)amino)naphthalene-1-sulfonate (AEDANS) residues were placed
      as the acceptors at solvent-exposed sites of Bc-Csp. Their R0 value of about 22 A
      was well suited for following distance changes during the folding of this protein
      with a high sensitivity. The mutagenesis and the labeling did not alter the
      refolding kinetics. The changes in energy transfer during folding were monitored
      by both donor and acceptor emission and reciprocal effects were found. In two
      cases the donor-acceptor distances were similar in the unfolded and the folded
      state and, as a consequence, the kinetic changes in energy transfer upon folding
      were very small. For four donor/acceptor pairs we found that > or =50% of the
      increase in energy transfer upon folding occurred prior to the rate-limiting step
      of folding. This reveals that about half of the shortening of the intra-molecular
      distances upon folding has occurred already before the rate-limiting step and
      suggests that the fast two-state folding reaction of Bc-Csp is preceded by a very
      rapid collapse.

PMID- 14729347
TI  - Understanding protein-ligand interactions: the price of protein flexibility.
AB  - In order to design selective, high-affinity ligands to a target protein, it is
      advantageous to understand the structural determinants for protein-ligand complex
      formation at the atomic level. In a model system, we have successively mapped the
      factor Xa binding site onto trypsin, showing that certain mutations influence
      both protein structure and inhibitor specificity. Our previous studies have shown
      that introduction of the 172SSFI175 sequence of factor Xa into rat or bovine
      trypsin results in the destabilisation of the intermediate helix with burial of
      Phe174 (the down conformation). Surface exposure of the latter residue (the up
      conformation) is critical for the correct formation of the aromatic box found in
      factor Xa-ligand complexes. In the present study, we investigate the influence of
      aromatic residues in position 174. Replacement with the bulky tryptophan (SSWI)
      shows reduced affinity for benzamidine-based inhibitors (1) and (4), whereas
      removal of the side-chain (alanine, SSAI) or exchange with a hydrophilic residue
      (arginine, SSRI) leads to a significant loss in affinity for all inhibitors
      studied. The variants could be crystallised in the presence of different
      inhibitors in multiple crystal forms. Structural characterisation of the variants
      revealed three different conformations of the intermediate helix and 175 loop in
      SSAI (down, up and super-up), as well as a complete disorder of this region in
      one crystal form of SSRI, suggesting that the compromised affinity of these
      variants is related to conformational flexibility. The influence of Glu217,
      peripheral to the ligand-binding site in factor Xa, was investigated.
      Introduction of Glu217 into trypsin variants containing the SSFI sequence
      exhibited enhanced affinity for the factor Xa ligands (2) and (3). The crystal
      structures of these variants also exhibited the down and super-up conformations,
      the latter of which could be converted to up upon soaking and binding of
      inhibitor (2). The improved affinity of the Glu217-containing variants appears to
      be due to a shift towards the up conformation. Thus, the reduction in affinity
      caused by conformational variability of the protein target can be partially or
      wholly offset by compensatory binding to the up conformation. The insights
      provided by these studies will be helpful in improving our understanding of
      ligand binding for the drug design process.

PMID- 14729348
TI  - Structure of the haemagglutinin-neuraminidase from human parainfluenza virus type
      III.
AB  - The three-dimensional structure of the haemagglutinin-neuraminidase (HN) from a
      human parainfluenza virus is described at ca 2.0 A resolution, both in native
      form and in complex with three substrate analogues. In support of earlier work on
      the structure of the homologous protein from the avian pathogen Newcastle disease
      virus (NDV), we observe a dimer of beta-propellers and find no evidence for
      spatially separated sites performing the receptor-binding and neuraminidase
      functions of the protein. As with the NDV HN, the active site of the HN of
      parainfluenza viruses is structurally flexible, suggesting that it may be able to
      switch between a receptor-binding state and a catalytic state. However, in
      contrast to the NDV structures, we observe no ligand-induced structural changes
      that extend beyond the active site and modify the dimer interface.

PMID- 14729349
TI  - Lens and retina regeneration: transdifferentiation, stem cells and clinical
      applications.
AB  - In this review we present a synthesis on the potential of vertebrate eye tissue
      regeneration, such as lens and retina. Particular emphasis is given to two
      different strategies used for regeneration, transdifferentiation and stem cells.
      Similarities and differences between these two strategies are outlined and it is
      proposed that both strategies might follow common pathways. Furthermore, we
      elaborate on specific clinical applications as the outcome of regeneration-based
      research.

PMID- 14729350
TI  - Control of mucin production by ocular surface epithelial cells.
AB  - Multiple species of mucins are synthesized and secreted by corneal and
      conjunctival epithelial cells. These mucins are vital components of the tear film
      protecting the ocular surface from the external environment by providing a
      physical and chemical barrier. The release of mucins must be tightly regulated as
      both mucin overproduction and underproduction cause ocular surface disorders.
      Mucin production can be regulated by controlling mucin synthesis, mucin release,
      or proliferation of the cells that produce the mucin. This review will focus on
      the evidence demonstrating the control of the mechanisms responsible for
      production of mucins, their secretion, and corneal and conjunctival epithelia
      cell proliferation. By understanding these mechanisms under normal conditions,
      treatments can be designed for diseases of the mucous production of the ocular
      surface.

PMID- 14729351
TI  - Comparative anatomy of nitrergic intrinsic choroidal neurons (ICN) in various
      avian species.
AB  - Intrinsic choroidal neurons (ICN) represent a peculiar feature of eyes in higher
      primates and birds. They account for up to 2000 in human and duck eyes but are
      virtually absent or rare in all other mammalian species investigated so far. It
      has been suggested that ICN are involved in regulation of ocular blood supply,
      hence influencing intraocular pressure, and changes in choroidal thickness, thus
      influencing accommodation. The present study was undertaken in order to compare
      differences in various avian species with respect to ICN as well as to provide
      data on some avian species relevant for experimental ophthalmic research, i.e.
      chicken and quail. Choroids from 12 avian species were processed for NADPH
      diaphorase histochemistry or, in some cases, neuronal nitric oxide synthase
      immunocytochemistry. ICN were quantified and normalized to mean choroidal area.
      Three choroids of each galliformes (i.e. chicken, quail, turkey) and anseriformes
      (i.e. Muscovy duck, Mallard duck, goose) were rastered in squares of 1 mm2 and
      x/y coordinates were transferred into a 3D-diagram with the amount of ICN
      represented in the z-axis. ICN were detected in all species investigated. They
      were predominantly small cells with soma diameters of 20-30 microm. In turkey,
      and to a lesser amount in chicken, a subpopulation of ICN with somal diameters of
      up to 70 microm was observed. Highest mean cell counts were found in goose
      (6195.4; turkey 3558.4; chicken 1681.4; Muscovy duck 785.4; Mallard duck 640.8;
      quail 440.2). Normalized to choroidal area, highest mean cell counts were (per
      mm2): 12.62 in goose, 4.42 in both chicken and turkey, 2.86 in quail, 2.66 in
      Mallard duck and 1.89 in Muscovy duck. In galliformes, ICN were found to be
      accumulated temporo-cranial, while in anseriformes they were arranged in a more
      belt-like fashion, passing from cranio-nasal to temporo-caudal. Our results show
      that besides Muscovy duck, other avian species appear as suitable models for
      further functional experiments on ICN. The temporo-cranial accumulation of ICN in
      galliformes and the belt-like arrangement in anseriformes may reflect special
      functional requirements in regions of high visual acuity.

PMID- 14729352
TI  - Regulation of the ubiquitin proteasome pathway in human lens epithelial cells
      during the cell cycle.
AB  - Most proliferating cells follow a series of orderly transitions from one phase to
      another. These transitions are usually controlled by timed degradation of cell
      cycle regulators by the ubiquitin-proteasome pathway (UPP). There are no
      published reports regarding the timing of phases of the human lens cell cycle or
      regarding cell cycle-related changes in UPP components. Objectives of this study
      were to characterize the timing of the phases of the human lens epithelial cell
      cycle and to explore potential functions of critical components of the UPP in
      controlling lens cell cycle. Human lens epithelial cells were synchronized at
      G0/G1 phase by contact inhibition. Cell cycle progression upon subculturing was
      monitored by FACS analysis. It took approximately 40 hr for HLEC to complete one
      cell cycle, approximately 20 hr for G1 phase, approximately 8-10 hr for S phase
      and approximately 10 hr for the combination of G2 and M phases. Proteasome
      dependent degradation of p21WAF and p27Kip, the dominant Cdk inhibitors, was
      associated with the G1/S phase transition in these cells. Proteasome inhibition
      experiments indicate that proteolysis is the predominant process which is
      responsible for the variations in these regulators during the cell cycle. Levels
      of specific ubiquitin conjugating enzymes, Ubc7 and Ubc10, increased 6 and 2-fold
      at the G2/M phase and S/G2/M phases, respectively. Levels of these E2s decreased
      precipitously upon completion of the M phase. In contrast, levels of ubiquitin
      activating enzyme (E1) and Ubc3 remained constant during the cell cycle. Cul1, a
      component of the SCF (an E3), remained relatively constant during cell cycle. The
      up-regulation of Ubc7 and Ubc10 during the G2/M and S/G2/M phases suggests that
      these enzymes may be involved in controlling the cell cycle progression at this
      phase. Taken together, the data indicate that expression of key components of the
      UPP in the human lens epithelial cells is regulated in a cell cycle-dependent
      manner. Some of the variations in levels of ubiquitin conjugating enzymes are
      suggestive of previously undescribed functions.

PMID- 14729353
TI  - Expression of endoglin in choroidal neovascularization.
AB  - Endoglin (CD105) is a membrane protein involved in the TGF-beta receptor
      signalling pathway with predominant expression by proliferating endothelial
      cells. The aim of this study is to analyze the expression of Endoglin in
      choroidal neovascularization membranes (CNVM) and to compare it to the overall
      proliferative status of CNVM. Thirty surgically excised CNVM, secondary to age
      related macular degeneration, were investigated using light microscopic
      immunohistochemistry and confocal immunofluorescence microscopy using verified
      antibodies directed against the endothelial cell markers Endoglin, von Willebrand
      factor (vWF) and CD34 and the proliferation marker Ki-67. Donor eyes were used as
      controls. A selective expression of CD34 and vWF as well as Endoglin was found in
      endothelial cells. Endoglin expression was elevated in vascular endothelial cells
      contained within CNVM, but a moderate Endoglin expression could also be
      visualized in quiescent CD34 and vWF positive ocular vasculature. Ki-67 positive
      cells were detected in CNVM, but these were rarely endothelial cells. Endoglin
      expression in endothelial cells of CNVM is increased, but rarely associated with
      a concomitant expression of the proliferation marker Ki-67. The elevated
      expression of Endoglin in surgically excised CNVM suggests a persisting post
      mitotic activation in an advanced stage of this neovascular tissue.

PMID- 14729354
TI  - Dorzolamide induces vasodilatation in isolated pre-contracted bovine retinal
      arteries.
AB  - The effect of the carbonic anhydrase inhibitor dorzolamide on vascular smooth
      muscle in pre-contracted bovine retinal arteries was examined. Ring segments of
      retinal arteries were placed in a small vessel myograph for measurement of
      contractile activity. The arteries were placed in a physiological saline
      solution. Vasoconstriction was induced by either 124 mM KCl (0.90 +/- 0.46 mN,
      n=34), 10(-4) M prostaglandin F2alpha (1.72 +/- 0.84 mN, n=10) or 10(-6) M
      norepinephrine (0.78 +/- 0.47 mN, n=6). Both KCl and prostaglandin F2alpha caused
      steady repeatable contractions but norepinephrine caused a single phasic
      contraction. The effect of the carbonic anhydrase inhibitor, dorzolamide on the
      vasoconstriction was examined. Dorzolamide, if added to the bath when the
      vasoconstriction had reached a maximum steady level, caused a highly significant
      relaxation (vasodilatation) of the arteries. This action of dorzolamide occurred
      irrespective of which agent was used to induce vasoconstriction. Similar results
      were obtained in experiments were Hepes buffer was used instead of
      CO2/bicarbonate buffer. The vasodilatation induced by dorzolamide was stable as
      long as the drug remained in the bath, and was reversible. These results show
      that dorzolamide causes a vasodilatation of retinal arteries, pre-contracted by
      three different mechanisms by direct action and presumably independent of changes
      in extracellular pH.

PMID- 14729355
TI  - Pigment epithelium-derived factor in the monkey retinal pigment epithelium and
      interphotoreceptor matrix: apical secretion and distribution.
AB  - Pigment epithelium-derived factor (PEDF) is an extracellular protein derived from
      the retinal pigment epithelium (RPE), a tissue formed by polarized cells that
      release growth and trophic factors in a directional fashion. We have investigated
      the distribution and directional release of PEDF protein by the monkey RPE. We
      established primary cultures of monkey RPE cells that expressed the PEDF gene,
      and that synthesized and secreted the PEDF protein. Northern analysis of RPE
      cultures and monkey ocular tissues showed that PEDF transcripts were highly
      expressed in RPE as compared with several other monkey ocular tissues, being even
      more abundant in cultured cells than they were in the native RPE. The
      differentiated RPE cells in culture secreted protein that shared the
      immunological, biochemical and biological characteristics of PEDF. The overall
      PEDF levels in the RPE conditioned media reached 6.5 mg ml- after 8 days in
      culture (i.e. 1.1 pg of PEDF per RPE cell). RPE cells were cultivated on
      permeable supports as monolayers forming a barrier between apical and basal
      compartments. Apical and basal culture media were sampled at three or four-day
      intervals for 18 cycles, and the PEDF content was quantified. Most of the PEDF
      protein was significantly higher in the apical than in the basal medium (>4
      times) at the initial recovery intervals, to be detected only in the apical
      medium at the latter intervals. In the native monkey eye, the concentration of
      soluble PEDF in the interphotoreceptor matrix (144 nM) was 7-fold and 25-fold
      greater than in vitreous and aqueous, respectively. PEDF was abundant in the
      interphotoreceptor matrix surrounding rod and cone outer segments, and was
      detectable at lower levels in the RPE as visualized by confocal microscopy. We
      concluded that PEDF synthesized by the RPE is secreted preferentially from the
      apical surface and is distributed apically to the RPE bordering the outer
      segments of photoreceptors. PEDF can be a useful marker for RPE polarization and
      differentiation. The polarization of RPE may be an important mechanism to control
      PEDF secretion and our results offer interesting possibilities on regulation of
      PEDF.

PMID- 14729356
TI  - The effects of oxidative stress on telomerase activity and other stress-related
      proteins in lens epithelial cells.
AB  - Telomerase is a ribonucleoprotein complex responsible for maintaining the ends of
      chromosomes and for repair of DNA strand breaks. While telomerase activity is
      generally found in cells that have unlimited proliferative potential such as
      neoplastic cells, germline cells and some stem cells, lens epithelial cells
      (though not highly proliferative) have telomerase activity. Our previous studies
      indicated that lens epithelial cells express high levels of telomerase despite
      their low proliferative potential, thus we hypothesized that telomerase
      expression protects lens epithelial cells from oxidative stress. We also
      determined levels of the stress proteins gadd45 and p16 and the stress and
      proliferation-related protein, proliferating cell nuclear antigen (PCNA). In
      acute studies, lenses were exposed to TBHP for 0-120 min. In recovery studies,
      lenses were exposed to TBHP for 1 hr, then allowed to recover for up to 18 hr. In
      acute studies, telomerase activity was increased, p16 initially decreased then
      normalized, PCNA levels did not change significantly even in the overnight
      recovery groups, and gadd45 was decreased in some TBHP exposed groups. In
      recovery studies, telomerase activity was increased in all groups, gadd45
      decreased then became elevated, and p16 levels were decreased at later recovery
      times. PCNA levels remained constant during the studies, indicating that there
      was no change in proliferation. These studies showed that elevated telomerase
      activity did not correlate with increased proliferation in lens epithelial cells;
      instead, increased telomerase activity was associated with increased levels of
      the stress-related protein gadd45 only in the later recovery times. These
      findings support the hypothesis that telomerase plays a protective rather than a
      proliferative role in lens epithelial cells.

PMID- 14729357
TI  - Characterization of beta amyloid assemblies in drusen: the deposits associated
      with aging and age-related macular degeneration.
AB  - PURPOSE: Recent studies strongly suggest that drusen, the extracellular deposits
      associated with age-related macular degeneration (AMD), are a manifestation of
      local inflammatory events. New evidence indicates that substructural elements
      within drusen contain activated complement components as well as amyloid beta
      (Abeta), a major pro-inflammatory component of Alzheimer's disease plaques. We
      characterized the ultrastructural organization and histochemical staining
      properties of these Abeta-containing elements in order to further assess their
      significance in drusen formation and AMD pathogenesis. METHODS: We used
      differential interference contrast optics, laser scanning confocal
      immunofluorescence, and immunogold electron microscopy to characterize the
      structural properties and molecular composition of Abeta-containing elements in
      drusen. We obtained estimates of their frequency from montages of electron
      micrographs gathered from 152 human donor eyes ranging from 9 to 91 years of age.
      RESULTS: Spherical Abeta-containing elements, which are typically organized as
      concentric ring-like structures, are common substructural components of drusen.
      They stain with thioflavin T, but are not stained by Congo red; nor do they bind
      cationic, lipophilic, or nucleic acid-binding fluorescent dyes.
      Ultrastructurally, they are composed of a central core, one or more concentric
      inner rings with intervening electron lucent layers, and an electron dense outer
      shell. Immunogold labeling indicates that most Abeta immunoreactivity is
      associated with the outer layers that consist of densely-packed spherical
      subunits. No longitudinally-oriented fibril arrays, characteristic of aggregated
      amyloid fibrils in the brain, are evident. Other prominent drusen-associated
      proteins including the terminal complement complex C5b-9, vitronectin,
      apolipoprotein E, serum amyloid P component, and ubiquitin are excluded from the
      spheres.Conclusions. These structures embedded in drusen appear to represent a
      new type of macromolecular assembly that contains Abeta as well as activated
      complement components. The presence of Abeta in these extracellular deposits is
      an additional indication that some of the pathogenic pathways that give rise to
      drusen and AMD may be shared with other neurodegenerative diseases characterized
      by misfolded protein deposition and aggregation.

PMID- 14729358
TI  - Comparison of morphological and functional characteristics of primary-cultured
      human conjunctival epithelium and of Wong-Kilbourne derivative of Chang
      conjunctival cell line.
AB  - PURPOSE: To analyze the relevance of a human conjunctival cell line in a study of
      conjunctival epithelium. We investigated and compared the effects of IFNgamma and
      TNFalpha in a primary culture of human conjunctiva and in a human conjunctival
      cell line. METHODS: A primary-cultured human conjunctival epithelium and a human
      conjunctival cell line (Chang cells) were treated for 72 hr with 20, 200, 400 and
      600 U ml(-1) IFNgamma or with 1100 and 11,000 U ml(-1) TNFalpha. Then, the
      expression of HLA DR, CD40, CD44, CD63, CD80, CD86, Fas receptor, E-cadherin,
      ICAM-1, MUC1, cytokeratins and vimentin were investigated by flow cytometry. Cell
      morphology was studied with phalloidin staining. Apoptosis was detected by flow
      cytometry with Annexin V and via cell cycle analysis. RESULTS: The primary
      culture of human conjunctival epithelium expressed cytokeratin K4, non
      keratinized squamous epithelial marker. Chang cells presented a more
      dedifferentiated phenotype and were cytokeratin K4 negative. In primary-cultured
      cells, IFNgamma (600 U ml(-1)) induced only a low level of apoptosis and a
      significant upregulation of most tested proteins such as HLA DR, Fas, ICAM-1,
      CD40 and CD63. In the Chang cell line, IFNgamma induced a significant level of
      apoptosis at concentrations of 200, 400 and 600 U ml(-1). HLA DR and CD63 were
      induced at lower levels than in primary-cultured cells. Other proteins were
      modified in a similar manner after IFNgamma treatment in both systems. In the
      primary-cultured cells, TNFalpha induced an important upregulation of ICAM-1, Fas
      and CD40 whereas CD44 and CD63 were significantly decreased. Conversely, only a
      very weak alteration of CD63 and ICAM-1 was observed in the Chang cell line after
      TNFalpha treatment. CONCLUSIONS: A primary culture of a human conjunctival
      epithelium demonstrated well-defined epithelial features. TNFalpha and IFNgamma,
      two inflammatory cytokines, induced different effects in both cellular systems,
      in a primary-cultured conjunctival epithelium and a human conjunctival cell line.
      Inflammation-related molecules were highly upregulated in the primary culture
      and, to a lesser extent, in the Chang cell line. Thus, the Chang cell line
      differs in certain features from a primary culture of human conjunctival
      epithelium, a fact which emphasizes the complexity of interpretation of in vitro
      data and this should be taken into consideration in in vitro studies of human
      conjunctival epithelium.

PMID- 14729359
TI  - Changes in gene expression in response to mechanical strain in human scleral
      fibroblasts.
AB  - Scleral fibroblasts are involved in scleral remodeling during axial elongation in
      myopia. Mechanical load is a potent stimulator of gene expression. This study
      seeks to identify changes in gene expression of scleral fibroblasts in response
      to mechanical load and speculate on possible mechanisms of scleral remodeling in
      the development of myopia. Human scleral fibroblasts (HSFs) were mechanically
      stretched for 30 min and 24 hr. A gene microarray analysis was used to measure
      changes in gene expression. A total of 237 genes revealed differential and
      significant changes in expression (P<0.01) after 30 min of stretching. Of these,
      28 unexpressed genes began to be expressed (turned on), while 31 expressed genes
      were no longer expressed (turned off). After 24 hr, 308 genes showed reproducible
      changes in expression (P<0.01), while 29 genes were turned on and 17 genes were
      turned off. After 30 min, 25 genes showed at least a threefold change in
      expression. These included genes for cell receptors, protein kinases, cell
      growth/differentiation factors, extracellular matrix (ECM) proteins, lipid
      metabolism, protein metabolism, transcription factors, binding proteins and water
      channels. After 24 hr, 21 genes showed at least a threefold change in expression.
      These included genes for cell receptors, protein kinases, cell
      growth/differentiation factors, lipid metabolism, ECM proteins, transcription
      factors, and carbohydrate metabolism. RT-PCR and Southern blotting confirmed the
      changes in expression of selected genes. In this study we identified a large
      number of early and late mechanical response genes in HSFs. These changes in gene
      expression will provide potential candidate genes that might be involved in
      scleral remodeling during axial elongation in myopia.

PMID- 14729360
TI  - Effects of prostaglandin F2alpha, latanoprost and carbachol on phosphoinositide
      turnover, MAP kinases, myosin light chain phosphorylation and contraction and
      functional existence and expression of FP receptors in bovine iris sphincter.
AB  - A potential role for myosin light chain kinase (MLCK) in regulating intraocular
      pressure and outflow function has recently been reported in living monkey eye and
      rabbit eye. There is little information about the effects of the ocular
      hypotensive agents, prostaglandin F2alpha (PGF2alpha) and latanoprost on this
      signaling pathway in ocular tissues. The aim of this study was to determine the
      agonist activity of PGF2alpha, latanoprost and carbachol (CCh) on the MLCK
      pathway in isolated bovine iris sphincter and furthermore to investigate the
      existence of the FP receptor in this tissue. In the present studies on the MLCK
      pathway four signal transduction mechanism assays were employed, phosphoinositide
      (PI) turnover, p42/p44 MAP kinase phosphorylation and activation, MLC
      phosphorylation and contraction. In the studies on the existence of the FP
      receptor in the bovine iris sphincter, the pharmacology and expression of the FP
      receptor protein, using a polyclonal anti-FP-receptor antibody and Western blot
      analysis, were determined. The data obtained on the MLCK pathway showed that the
      three agonists stimulated the biochemical and pharmacological responses in a
      concentration and time-dependent manner and that the order of potency and
      efficacy is PGF2alpha>latanoprost>CCh. The EC50 values in the PI turnover, MAP
      kinase phosphorylation, MLC phosphorylation and contraction assays were for
      PGF2alpha: 9, 42, 200 and 140 nM, respectively, for latanoprost: 13, 59, 250 and
      828 nM, respectively, and for CCh: 22, 200, 630 and 910 nM, respectively.
      Wortmannin, a selective inhibitor of MLCK, dose-dependently inhibited MLC
      phosphorylation and contraction induced by PGF2alpha, demonstrating a close
      relationship between activation of the MLCK pathway and contraction. The
      pharmacological studies showed that in the concentration range of 1 nM to 10
      microM, the FP-receptor agonists caused concentration-response curves with the
      following order of potencies: 17-phenyl trinor PGF2alpha (bimatoprost
      acid)>PGF2alpha>cloprostenol>latanoprost>latanoprost acid>bimatoprost
      amide>>fluprostenol. Immunoblot analysis of the FP receptor demonstrated
      expression of the prostaglandin FP receptor protein in this smooth muscle. These
      results clearly indicate that the MLCK signaling pathway is involved in the FP
      receptor function of the bovine iris sphincter and furthermore demonstrate that
      functional FP receptors exist and are expressed in this tissue.

PMID- 14729361
TI  - Lens regeneration in mice: implications in cataracts.
AB  - Lens regeneration in adult mice is possible when the lens capsule is left behind
      after lentectomy. The lens is regenerated by the remaining adherent lens
      epithelial cells, which differentiate to form lens fibres within days, showing
      normal morphology and bow regions. Epithelial to mesenchymal cell transformation
      is also seen during the early stages. The mouse, therefore, can become an
      indispensable animal model for cataract research, surgery and therapy.

PMID- 14729362
TI  - Cluster analysis of genes with significant change in expression in cells
      conditioned to survive TBOOH.
AB  - Immortal murine lens epithelial cells, alphaTN4-1 have been conditioned to
      survive H2O2, H cells, or TBOOH, T cells, at concentrations that will cause
      cataract in vitro. Since H cells are killed by TBOOH but T cells survive H2O2, it
      is of interest to examine the gene expression of these cell lines. We now report
      the results of cluster analysis of genes whose expression is significantly
      changed by TBOOH. The analysis has revealed a small group of antioxidative
      defense genes that contribute to the survival of T and H cells when exposed to
      oxidative stress.

PMID- 14729363
TI  - Comment on 'Integrin alphavbbeta is not required for the phagocytosis of
      photoreceptor outer segments by cultured retinal pigment epithelial cells' by
      M.O. Hall, T.A. Abrams and B.L. Burgess [Exp. Eye Res. 77 (2003) 281-286].

PMID- 14729365
TI  - Cytogenetic biomonitoring of a floriculturist population in Italy: micronucleus
      analysis by fluorescence in situ hybridization (FISH) with an all-chromosome
      centromeric probe.
AB  - Flower production in greenhouses associated with a heavy use of pesticides is
      very wide-spread in the western part of the Ligurian region (Italy). The
      formation of micronuclei in peripheral blood lymphocytes is a valuable
      cytogenetic biomarker in human populations occupationally exposed to genotoxic
      compounds. In the present study we investigated the micronucleus frequency in
      peripheral blood lymphocytes of 52 floriculturists and 24 control subjects by use
      of the cytokinesis-block methodology associated with fluorescence in situ
      hybridization with a pan-centromeric probe that allowed to distinguish centromere
      positive (C+) and centromere-negative (C-) micronuclei. The comparison between
      floriculturists and controls did not reveal any statistically significant
      difference in micronucleus frequency, although an increase was observed with
      increasing pesticide use, number of genotoxic pesticides used and duration of
      exposure. An increase in C+ as well as in C- micronuclei and in the percentage of
      C+ micronuclei with respect to the total number of micronuclei was detected in
      floriculturists, suggesting a higher contribution of C+ micronuclei in the total
      number scored. The percentage C+ micronuclei was not related to the duration of
      exposure or to the number of genotoxic pesticides used, but a higher percentage
      (66.52% versus 63.78%) was observed in a subgroup of subjects using
      benzimidazolic compounds, compared with the floriculturist population exposed to
      a complex pesticide mixture not including benzimidazolics. These results suggest
      a potential human hazard associated with the exposure to this class of aneuploidy
      inducing carcinogens.

PMID- 14729366
TI  - Comet assay and micronucleus test in circulating erythrocytes of Cyprinus carpio
      specimens exposed in situ to lake waters treated with disinfectants for
      potabilization.
AB  - The detection of a possible genotoxic effect of surface water treated with
      disinfectants for potabilization is the aim of the present work. The Comet assay
      and the micronucleus test were applied in circulating erythrocytes of Cyprinus
      carpio. Young specimens (20-30 g) were exposed in experimental basins, built
      within the potabilization plant of Castiglione del Lago (Perugia, Italy). In this
      plant the water of the Trasimeno Lake is treated and disinfected for
      potabilization before it is distributed to the people in the net of drinkable
      water. A continuous flow of water at a constant rate was supplied to basins; the
      water was continuously treated at a constant concentration with one of the three
      tested disinfectants (sodium hypochlorite, peracetic acid and chloride dioxide),
      one control basin being supplied with untreated water. Three sampling campaigns
      were performed: October 2000, February 2001 and June 2001. Repeated blood
      samplings through intracardiac punctures allowed to follow the same fish
      populations after different exposure times: before introduction of the
      disinfectant, and 10 or 20 days afterwards. An additional blood sampling was
      performed 3 h after addition of the disinfectant in other, simultaneously
      exposed, fish populations. Genotoxic damage was shown in fish exposed to water
      disinfected with sodium hypochlorite and chloride dioxide. The Comet assay showed
      an immediate response, i.e. DNA damage that was induced directly in circulating
      erythrocytes, whereas micronuclei reached their highest frequencies at later
      sampling times, when a genotoxic damage in stem cells of the cephalic kidney is
      expressed in circulating erythrocytes. The quality of the untreated surface water
      seems to be the most important parameter for the long-term DNA damage in
      circulating erythrocytes.

PMID- 14729367
TI  - Assessment of DNA damage in glue sniffers by use of the alkaline comet assay.
AB  - Toluene is used widely, not only in industry, but also in households where
      toluene exposure and abuse can occur. To estimate the genotoxic risk of toluene
      exposure, DNA damage was determined in peripheral lymphocytes of 20 glue sniffers
      and 20 age-matched controls by use of the alkaline comet assay. Urinary hippuric
      acid and o-cresol excretion rates, which are used as a marker for toluene
      exposure, were also measured in sniffers and compared with historical control
      values. The increase in genetic damage in sniffers was statistically significant
      as compared to control subjects (P<0.0001). The mean values of the hippuric acid
      and o-cresol excretion rate for glue sniffers was 73- and 1582-fold higher,
      respectively, than in controls and confirms the putative exposure. Education of
      the general public and efforts to keep adolescents away from volatile solvent
      based products, which may lead to a desire of sniffing in the future, would be
      advisable.

PMID- 14729368
TI  - Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in
      the rat lung.
AB  - Asphalt fumes are complex mixtures of aerosols and vapors containing various
      organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously,
      we have demonstrated that inhalation exposure of rats to asphalt fumes resulted
      in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1
      and increased phase II enzyme quinone reductase activity in the rat lung. In the
      present study, the potential genotoxic effects of asphalt fume exposure due to
      altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt
      fume generated under road paving conditions at various concentrations and
      sacrificed the next day. Alveolar macrophages (AM) were obtained by
      bronchoalveolar lavage and examined for DNA damage using the comet assay. To
      evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in
      bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various
      exposure groups was isolated from tissue homogenates and characterized for
      metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene
      (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and
      YG1029. This study showed that the paving asphalt fumes significantly induced DNA
      damage in AM, as revealed by DNA migration in the comet assay, in a dose
      dependent manner, whereas the micronuclei formation in bone marrow PCEs was not
      detected even at a very high exposure level (1733 mg h/m3). The conversion of 2
      AA to mutagens in the Ames test required lung S9-mediated metabolic activation in
      a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed
      to asphalt fume at a total exposure level of 479+/-33 mg h/m3 did not
      significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or
      YG1029. At a higher total asphalt fume exposure level (1150+/-63 mg h/m3), S9
      significantly increased the mutagenicity of 2-AA as compared to the control.
      However, S9 from asphalt fume-exposed rats did not significantly activate the
      mutagenicity of BaP in the Ames test. These results show that asphalt fume
      exposure, which significantly altered both phases I and II metabolic enzymes in
      lung microsomes, is genotoxic to AM and enhances the metabolic activation of
      certain mutagens through altered S9 content.

PMID- 14729369
TI  - The c-myc activation in cervical carcinomas and HPV 16 infections.
AB  - Despite the prominent role for Human Papillomavirus (HPV) infection in the
      development of genital cancer, other genetic or environmental co-factors have
      also been involved. Studies of c-myc activation in cervical carcinomas have
      reported that gene over-expression (mainly gene amplification) are common in
      cervical squamous cell carcinomas and may correlate with the biologic behavior of
      the neoplasm. Using PCR based technology, DNAs from 79 normal cervical samples
      and 225 abnormal cervical tissue scrapes were analyzed for HPV detection and
      typing and for c-myc gene amplification. Significant differences were found
      between the different cyto/histology groups (P<0.0001) and also with HPV high
      risk infected samples (P<0.0002). In this sense, we showed that the average c-myc
      copy number increased according to the histological grade of the lesion (OR=6.3,
      CI=2.1-18.8). Also, the results showed that the infection with HPV 16 was tightly
      associated with c-myc amplification (OR=10.6, CI=3.1-36). These results could
      indicate that oncogene amplification take place in pre-invasive stages of
      cervical disease and could cooperate not only in tumor progression but also in
      cell transformation. Moreover, the results strongly associate the c-myc gene
      amplification to the infection with the oncogenic HPV 16, showing that the
      pattern of virus infection and oncogene activation could be specific for
      different viral genotypes.

PMID- 14729370
TI  - Metabolic activation of 10-aza-substituted benzo[a]pyrene by cytochrome P450 1A2
      in human liver microsomes.
AB  - We previously reported that 10-azabenzo[a]pyrene (10-azaBaP), a 10-aza-analog of
      BaP and an environmental carcinogen, showed greater mutagenicity than BaP in the
      Ames test using pooled human liver S9. To investigate the cytochrome P450 (CYP)
      isoform involved in the activation of 10-azaBaP to the genotoxic form, the
      mutagenicity of 10-azaBaP using nine individual donors' and pooled human liver
      microsome preparations was compared with each CYP activity. Induced revertants by
      2.5 nmol per plate 10-azaBaP with 0.5 mg per plate human liver microsomal protein
      showed a large inter-individual variation (42-fold) among the nine donors. The
      number of induced revertants highly correlated with the CYP1A2-selective
      catalytic activity from each microsome preparation, and no correlation was
      observed with other CYP isoform-selective catalytic activities. Moreover,
      recombinant human CYP1A2 contributed to the mutagenicity of 10-azaBaP more
      markedly than recombinant human CYP1A1. These results suggest that CYP1A2 may be
      the principal enzyme responsible for the metabolic activation of 10-azaBaP in
      human liver microsomes. With regard to the proposal that BaP may be activated by
      human CYP1A1, our results suggest that the nitrogen-substitution at position-10
      of BaP may cause the CYP enzyme-specificity in metabolic activation to change
      from CYP1A1 to CYP1A2.

PMID- 14729371
TI  - Genotoxic effects of a complex mixture adsorbed onto ambient air particles on
      human cells in vitro; the effects of Vitamins E and C.
AB  - Genotoxicity of complex mixtures of organic compounds adsorbed onto ambient air
      particles (extractable organic matter, EOM) collected in Teplice (Czech Republic)
      as well as genotoxicity of the indirectly acting carcinogens benzo[a]pyrene
      (B[a]P) and 5,9-dimethyl-7H-dibenzo[c,g]carbazole (5,9-diMeDBC) was studied in
      human HepG2 and Caco-2 cells cultured in vitro. The level of DNA breaks was
      detected by conventional single-cell gel electrophoresis (alkaline comet assay).
      The level of DNA breaks+oxidative DNA lesions was assessed by modified single
      cell gel electrophoresis. The indirectly acting chemical carcinogens studied were
      able to induce DNA breaks as well as oxidative DNA damage in both cell lines, but
      stronger DNA-damaging effects were observed in HepG2 cells, which contain a
      higher level of metabolic enzymes. Treatment of cells with the complex mixtures
      showed a dose-dependent increase of DNA breaks in HepG2 cells as well as in Caco
      2 cells, with seasonal differences. Winter samples of EOM from Teplice (TP-W)
      were more effective in inducing DNA damage than summer samples (TP-S). Both
      mixtures caused significant oxidative DNA damage in HepG2 cells. The effect was
      less evident in cells treated with higher concentrations of TP-W, since the comet
      assay is limited by saturation at a higher level of DNA damage. Possible
      reduction of B[a]P-, 5,9-diMeDBC- or EOM-induced DNA damage by Vitamins E and C
      was evaluated in HepG2 cells only. Pre-treatment of these cells with either one
      of the vitamins considerably reduced the levels of both DNA breaks and oxidative
      DNA lesions induced by all compounds investigated.

PMID- 14729372
TI  - Anticlastogenicity of chlorophyllin in the different cell cycle phases in
      cultured mammalian cells.
AB  - Chlorophyllin (Chln), a sodium-copper salt derivative of chlorophyll, like
      chlorophyll-a and -b found in green plants, has been studied for its protective
      action against the carcinogenic effects of various physical and chemical agents
      and in relation to the mutagenic and clastogenic activities of genotoxic agents.
      The aim of the present study was to evaluate chlorophyllin in different phases of
      the cell cycle for clastogenicity and anticlastogenicity, the latter in reversing
      DNA damage induced by ethyl methane sulfonate (EMS). The test for chromosomal
      aberrations was performed in cultured mammalian cells (CHO-K1). The three Chln
      concentrations tested (6.25, 12.5 and 25 microg/ml) were not clastogenic and
      damage induced by EMS (1240 microg/ml) was reduced in cells treated with Chln as
      well during S (25-48%) and G2/S (70-80%). The results demonstrate a greater
      protective effectiveness of Chln against EMS during G2/S.

PMID- 14729373
TI  - Evaluation of DNA damage in a population of bats (Chiroptera) residing in an
      abandoned monazite mine.
AB  - Ionising radiation has the ability to induce DNA damage. While the effects of
      high doses of radiation of short duration have been well documented, the
      biological effects of long-term exposure to low doses are poorly understood. This
      study evaluated the clastogenic effects of low dose ionising radiation on a
      population of bats (Chiroptera) residing in an abandoned monazite mine. Bats were
      sampled from two chambers in the mine, where external radiation levels measured
      around 20 microSv/h (low dose) and 100 microSv/h (higher dose), respectively. A
      control group of bats was sampled from a cave with no detectable radiation above
      normal background levels. The micronucleus assay was used to evaluate residual
      radiation damage in binucleated lymphocytes and showed that the micronucleus
      frequency per 500 binucleated lymphocytes was increased in the lower radiation
      exposed group (17.7) and the higher radiation-exposed group (27.1) compared to
      the control group (5.3). This study also showed that bats exposed to radiation
      presented with an increased number of micronuclei per one thousand reticulocytes
      (2.88 and 10.75 in the lower and high radiation-exposed groups respectively) when
      compared to the control group (1.7). The single-cell gel electrophoresis (comet)
      assay was used as a means of evaluating clastogenecity of exposure to radiation
      at the level of individual cells. Bats exposed to radiation demonstrated
      increased DNA damage as shown by the length of the comet tails and showed an
      increase in cumulative damage. The results of the micronucleus and the comet
      assays indicated not only a statistically significant difference between test and
      control groups (P<0.001), but also a dose-dependent increase in DNA damage
      (P<0.001). These assays may thus be useful in evaluating the potential
      clastogenecity of exposure to continuous low doses of ionising radiation.

PMID- 14729374
TI  - An assay method for the prediction of tumor promoting potential of chemicals by
      the use of Bhas 42 cells.
AB  - It has become an important task to develop a simple in vitro method for the
      detection of non-genotoxic carcinogens, among which tumor promoters are included.
      Bhas 42 cells are v-Ha-ras-transfected BALB/c 3T3 cells and are regarded as
      initiated cells in the 2-stage transformation paradigm. We designed a method for
      detecting tumor promoters by the use of Bhas 42 cells at advanced passage
      generation. In this method, the cells are cultured in six-well plates for 17 days
      during which test chemicals are added in the medium for 11 days from days 3 to
      14. The end-point of the assay is the induction of transformed foci. When the
      tumor promoter TPA was used, a significant number of transformed foci were
      induced concentration-dependently, whereas only a few foci were observed in
      control cultures. When various chemicals were examined by the method, a
      reasonable correlation was observed with the reported tumor-promoting ability in
      animal experiments. We propose that the Bhas 42 cell transformation method is
      practical and useful for the detection of tumor promoters.

PMID- 14729375
TI  - Inhibition of B(a)P induced strand breaks in presence of curcumin.
AB  - Incidence of cancer at different sites may be related to oxidative damage to host
      genome by genotoxicants. These oxidative actions may be modified by
      phytochemicals present in foods. The non-nutritive dietary constituents which
      possess antimutagenic property appear to be promising chemopreventive agents.
      This study reports the protective effect of curcumin on B(a)P induced DNA damage
      in human peripheral blood lymphocyte cells. The study group consisted of 10 male
      smokers, 10 non-smokers and 10 non-smoking females aged between 25 and 45. The
      DNA damage was assessed using comet assay. In all the groups curcumin showed a
      dose-dependent inhibitory effect. The effect appeared to be sex dependent. There
      was no correlation between DNA damage and GST-Mu levels and levels of
      micronutrients namely Vitamins A, E and beta carotene. The results of this study
      are in line with our earlier observations on turmeric/curcumin as a potential
      chemopreventer.

PMID- 14729376
TI  - Inhibitory effect of trilinolein on angiotensin II-induced cardiomyocyte
      hypertrophy.
AB  - The myocardial protective effects of trilinolein, isolated from the Chinese herb
      Sanchi (Panax notoginseng), may be related to its antioxidant effects. In the
      present study, we investigated the effects of trilinolein on angiotensin II
      induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were
      stimulated with angiotensin II, [3H]leucine incorporation and the beta-myosin
      heavy chain promoter activity were examined. We also examined the effects of
      trilinolein on angiotensin II-induced intracellular reactive oxygen species
      generation. Trilinolein significantly inhibited angiotensin II-increased protein
      synthesis, beta-myosin heavy chain promoter activity, and intracellular reactive
      oxygen species generation. Antioxidant N-acetylcysteine also decreased
      angiotensin II-increased protein synthesis and beta-myosin heavy chain promoter
      activity. Furthermore, trilinolein and N-acetylcysteine decreased angiotensin II-
      or hydrogen peroxide (H2O2)-activated mitogen-activated protein kinases (MAPKs)
      phosphorylation, and activator protein-1 (AP-1)- [or nuclear factor-kappaB (NF
      kappaB)]-reporter activities. These data indicate that trilinolein inhibits
      angiotensin II-induced cardiomyocyte hypertrophy and beta-myosin heavy chain
      promoter activity via attenuation of reactive oxygen species generation.

PMID- 14729377
TI  - Inhibition of arachidonic acid release and cytosolic phospholipase A2 alpha
      activity by D-erythro-sphingosine.
AB  - Sphingolipid metabolites such as sphingosine 1-phosphate (S1P) and ceramide can
      mediate many cellular events including apoptosis, stress responses and growth
      arrest. Although ceramide stimulates arachidonic acid metabolism in several
      cells, the effects of sphingosine and its endogenous analogs have not been
      established. We investigated the effects of D-erythro-sphingosine and its
      metabolites on arachidonic acid release in the two cells and on the activity of
      cytosolic phospholipase A2alpha. C2-Ceramide (N-acetyl-D-erythro-sphingosine, 100
      microM) alone stimulated [3H]arachidonic acid release and enhanced the ionomycin
      induced release from the prelabeled PC12 cells and L929 cells. In contrast,
      exogenous addition of D-erythro-sphingosine inhibited the responses in a
      concentration-dependent manner in the two cell lines. D-erythro-sphingosine, D
      erythro-N,N-dimethylsphingosine (D-erythro-DMS) and D-erythro-dihydrosphingosine
      (D-erythro-DHS) significantly inhibited mastoparan-, but not Na3VO4-, stimulated
      arachidonic acid release in PC12 cells. D-erythro-S1P and DL-threo-DHS showed no
      effect on the responses. Production of prostaglandin F2alpha was also enhanced by
      C2-ceramide (20 microM) and suppressed by D-erythro-sphingosine (10 microM) in
      PC12 cells. An in vitro study revealed that D-erythro-sphingosine, D-erythro-DMS
      and D-erythro-DHS directly inhibited cytosolic phospholipase A2alpha activity.
      These findings suggest that ceramide and D-erythro-analogs of sphingosine have
      opposite effects on phospholipase A2 activity and thus regulate arachidonic acid
      release from cells.

PMID- 14729378
TI  - Influence of glucose concentration on the effects of aspirin, ticlopidine and
      clopidogrel on platelet function and platelet-subendothelium interaction.
AB  - Clinical studies have shown that the ability of aspirin to prevent
      cerebrovascular accidents is weaker in patients with diabetes. The aim of this
      study was to determine whether high concentrations of glucose modified the effect
      of aspirin, ticlopidine and clopigodrel on platelet function and platelet
      subendothelium interactions. This in vitro study tested three different
      concentrations of glucose. The effects were analyzed by comparing platelet
      aggregometry in whole blood, nitric oxide and prostacyclin production in cultures
      of human endothelial cells, and by quantitative analysis of morphological
      features of the platelet-subendothelium interaction under flow conditions. High
      concentrations of glucose increased platelet aggregation (13.9 Omega with 5 mM
      glucose vs. 21.6 Omega with 16.6 mM) and platelet-subendothelium interactions
      (28.9% with 5 mM glucose vs.35.2% with 16.6 mM), and decreased nitric oxide and
      prostacyclin production. In the presence of high concentrations of glucose, the
      antiaggregant effect of aspirin and its influence on nitric oxide production were
      diminished (IC50 54 microM with 5 mM glucose vs.556 microM with 16.6 mM glucose),
      and its effect on the platelet-subendothelium interaction was reduced (10.5%
      platelet occupancy with 5 mM glucose vs.23% with 16.6 mM glucose). The effects of
      ticlopidine and clopidogrel were not significantly modified.

PMID- 14729379
TI  - Celecoxib simulates respiratory burst through pertussis toxin-sensitive G
      protein, a possible signal for beta 2-integrin expression on human neutrophils.
AB  - The superoxide anion-generating effect of celecoxib (4-[5-(4-methylpheny)-3
      (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide); SC58633), a selective
      cyclooxygenase-2 inhibitor, on human neutrophils was evaluated in this study.
      Celecoxib induced superoxide anion generation in a concentration-dependent manner
      in human neutrophils. The EC50 value of celecoxib on superoxide anion generation
      was 15.5+/-2.5 microM. A NADPH oxidase inhibitor, diphenyliodonium (20 microM),
      and superoxide dismutase (150 U/ml) completely inhibited the free radical
      generation caused by celecoxib, indicating that the respiratory burst was
      activated by celecoxib. 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      tetrakis(acetoxymethyl ester) (BAPTA/AM;10 microM) and staurosporine (200 nM)
      completely inhibited the superoxide anion release caused by celecoxib,
      respectively. These data indicated that celecoxib increased superoxide anion
      release by increasing intracellular calcium and protein kinase C activation.
      Moreover, 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3
      a)pyrrolo(3,4-C)-carbazole (Go-6976; 1 microM) and 3-[1-[3-(amidinothio)propyl-1H
      indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide, methane sulfate (Ro-31-8220; 0.5
      microM), specific inhibitors of conventional protein kinase C isotypes (alpha,
      beta(I) and beta(II)), significantly inhibited superoxide anion release caused by
      celecoxib. Rottlerin (5 microM), a protein kinase C delta inhibitor, did not
      affect the free radical generation caused by celecoxib. Celecoxib caused
      translocation of protein kinase C alpha, beta(I) and beta(II) from the cytosol to
      the cellular membrane. 2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one
      (PD98059; 20 microM) and wortmannin (100 nM) did not decrease the superoxide
      anion generation caused by celecoxib, indicating that Mitogen-activated protein
      (MAP) kinase and phosphatidylinositol 3-kinase (PI3 kinase) were not involved in
      the respiratory burst induced by celecoxib. Pertussis toxin (2 microg/ml), a Gi
      protein sensitive inhibitor, significantly inhibited superoxide anion release.
      Moreover, pertussis toxin significantly inhibited intracellular calcium
      mobilization and protein kinase C alpha, beta(I) and beta(II) translocation from
      the cytosol to the membrane. Celecoxib increased beta(2)-integrin expression on
      human neutrophils and this effect was inhibited by BAPTA/AM (10 microM),
      superoxide dismutase (150 U/ml), genistein (25 microM) and PD98059 (20 microM).
      This information indicated that intracellular calcium, superoxide anion, tyrosine
      kinase and MAP kinase are involved in beta(2)-integrin expression. Furthermore,
      BAPTA/AM, superoxide dismutase and genistein inhibited celecoxib-increased MAP
      kinase activity, indicating that MAP kinase is a downstream signal for beta(2)
      integrin expression. In conclusion, celecoxib stimulates superoxide anion release
      from human neutrophils by activating pertussis toxin sensitive G-protein. An
      increase in intracellular calcium and protein kinase C alpha, beta(I) and
      beta(II) is involved in this process. Celecoxib also regulates beta(2)-integrin
      expression through superoxide anion release, tyrosine kinase and p42/p44 MAP
      kinase on human neutrophils.

PMID- 14729380
TI  - Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293
      cells.
AB  - Several antimalarial drugs are known to produce a QT interval prolongation via a
      blockade of the rapidly activating delayed rectifier K+ current (IKr), encoded by
      the human-ether-a-go-go-related gene (hERG). We investigated the influence of
      lumefantrine and its major metabolite desbutyl-lumefantrine, as well as
      halofantrine, chloroquine, and mefloquine, on wild type hERG K+ channels in
      stably transfected human embryonic kidney cells (HEK293) using the whole cell
      patch-clamp technique. All of the tested antimalarial drugs inhibited the hERG K+
      channels in a concentration- and time-dependent manner. Only halofantrine blocked
      hERG tail currents voltage-dependently. The ranking of the half-maximal
      inhibitory concentrations (IC50) of the antimalarials was: halofantrine (0.04
      microM)<chloroquine (2.5 microM)<mefloquine (2.6 microM)<desbutyl-lumefantrine
      (5.5 microM)<lumefantrine (8.1 microM). Lumefantrine and desbutyl-lumefantrine
      showed a slower inhibition of IKr than the other tested antimalarials. In
      conclusion, lumefantrine and desbutyl-lumefantrine inhibited significantly the
      hERG tail current with a higher IC50-value than mefloquine, chloroquine and
      halofantrine. This, together with the calculated cardiac safety indices, suggests
      that lumefantrine and desbutyl-lumefantrine have a weaker proarrhythmic potential
      than their comparator compounds.

PMID- 14729381
TI  - Influence of carbenoxolone on the anticonvulsant efficacy of conventional
      antiepileptic drugs against audiogenic seizures in DBA/2 mice.
AB  - Carbenoxolone, the succinyl ester of glycyrrhetinic acid, is an inhibitor of
      11beta-hydroxy steroid dehydrogenase and gap junctional intercellular
      communication. It is currently used in clinical treatment of ulcer diseases.
      Systemic administration of carbenoxolone (1-40 mg/kg, intraperitoneally (i.p.))
      was able to produce a dose-dependent decrease in DBA/2 audiogenic seizure
      severity score. Glycyrrhizin, an analogue of carbenoxolone inactive at the gap
      junction level, was unable to affect audiogenic seizures at doses up to 30 mg/kg.
      In combination with conventional antiepileptic drugs, carbenoxolone, 0.5 mg/kg,
      i.p., which per se did not significantly affect the occurrence of audiogenic
      seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine,
      diazepam, felbamate, gabapentin, lamotrigine, phenytoin, phenobarbital and
      valproate against sound-induced seizures in DBA/2 mice. This effect was not
      observed after the combination of glycyrrhizin (10 mg/kg, i.p.) with some
      conventional antiepileptic drugs. The degree of potentiation induced by
      carbenoxolone was greater for diazepam, felbamate, gabapentin, phenobarbital and
      valproate, less for lamotrigine, phenytoin and carbamazepine. This increase was
      associated with a comparable impairment in motor activity; however, the
      therapeutic index of combined treatment of antiepileptic drugs with carbenoxolone
      was more favourable than the combination with glycyrrhizin or saline. Since
      carbenoxolone did not significantly influence the total and free plasma levels of
      diazepam, felbamate, gabapentin, lamotrigine, phenytoin, phenobarbital, valproate
      and carbamazepine, pharmacokinetic interactions are not likely. However, the
      possibility that carbenoxolone can modify the brain clearance of the
      anticonvulsant drugs studied may not be excluded. In addition, carbenoxolone did
      not significantly affect the hypothermic effects of the anticonvulsants tested.
      In conclusion, carbenoxolone showed an additive anticonvulsant effect when
      administered in combination with some classical anticonvulsants, most notably
      diazepam, felbamate, gabapentin, phenobarbital, and valproate, implicating a
      possible therapeutic relevance of such drug combinations.

PMID- 14729382
TI  - Stress-induced increase of cortical dopamine metabolism: attenuation by a
      tachykinin NK1 receptor antagonist.
AB  - The present study examined the potential role of tachykinin NK1 receptors in
      modulating immobilisation stress-induced increase of dopamine metabolism in rat
      medial prefrontal cortex. In agreement with previous studies, 20 min
      immobilisation stress significantly increased medial prefrontal cortex dopamine
      metabolism as reflected by the concentration of the dopamine metabolite
      dihydroxyphenylacetic acid (DOPAC). Pretreatment with the high affinity,
      selective, tachykinin NK1 receptor antagonist (3(S)-(2-methoxy-5-(5
      trifluoromethyltetrazol-1-yl)-phenylmethyl amino)-2(S)-phenylpiperidine) ((S)
      GR205171, 10 mg/kg, s.c.), a dose that in ex vivo binding studies extensively
      occupied rat brain tachykinin NK1 receptors for approximately 60 min,
      significantly attenuated the stress-induced increase of mesocortical DOPAC
      concentration without affecting cortical DOPAC levels per se. In contrast,
      pretreatment of animals with the less active enantiomer (R)-GR205171 (10 mg/kg,
      s.c.), which demonstrated negligible tachykinin NK1 receptor occupancy ex vivo,
      failed to affect either basal or stress-induced DOPAC concentration in medial
      prefrontal cortex. Furthermore, pretreatment of animals with the
      benzodiazepine/GABAA receptor antagonist, flumazenil (15 mg/kg, i.p.), did not
      affect the ability of (S)-GR205171 to attenuate the increase of medial prefrontal
      cortex DOPAC concentration by acute stress. Results demonstrate that the
      selective tachykinin NK1 receptor antagonist, (S)-GR205171, attenuated the stress
      induced activation of mesocortical dopamine neurones by a mechanism independent
      of the benzodiazepine modulatory site of the GABAA receptor.

PMID- 14729383
TI  - Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats.
AB  - Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does
      tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the
      right carotid artery permanently ligated followed by 2.5 h of hypoxia (8%
      oxygen). Tamoxifen (10 mg/kg) or vehicle was given i.p. 5 min prior to hypoxia,
      or 5 min after reoxygenation, with a second dose given 6 h after the first. Brain
      damage was evaluated by weight deficit of the right hemisphere 22 days following
      hypoxia and gross and microscopic morphology. Tamoxifen pre-treatment reduced
      brain weight loss from 21.5+/-4.0% in vehicle pups (n=27) to 2.6+/-2.5% in the
      treated pups (n=22, P<0.05). Treatment 5 min after reoxygenation reduced brain
      weight loss from 27.5+/-4.0% in vehicle pups (n=42) to 12.0+/-3.9% in the treated
      pups (n=30, P<0.05). Tamoxifen reduces brain injury in the neonatal rat.

PMID- 14729384
TI  - Decreased postsynaptic dopaminergic and cholinergic functions in the
      ventrolateral striatum of spontaneously hypertensive rat.
AB  - Dopamine and acetylcholine receptor functions in spontaneously hypertensive rats
      (SHR) and in control progenitor Wistar-Kyoto (WKY) rats were assessed, using
      dopamine D1-like/D2-like receptor-mediated and acetylcholine receptor-mediated
      jaw movements as readout parameters. Spontaneous behaviours such as locomotor
      activity, vacuous chewing, grooming, sniffing and rearing occurred significantly
      more in SHR than in WKY rats. In the anaesthetised rats, a mixture of SKF 38393
      (5 micrograms), a dopamine D1-like receptor agonist, and quinpirole (10
      micrograms), a dopamine D2-like receptor agonist, readily produced repetitive jaw
      movements in WKY rats, but not SHR, when bilaterally injected into the
      ventrolateral striatum; such injections into the nucleus accumbens shell were
      ineffective in each strain. Bilateral injections of carbachol (2.5 micrograms
      each side), an acetylcholine receptor agonist, into the ventrolateral striatum
      elicited repetitive jaw movements in both SHR and WKY rats, but to a far less
      degree in SHR. The present study demonstrates that spontaneous behaviours are
      enhanced in SHR, and that postsynaptic dopamine D1-like/D2-like receptors and
      acetylcholine receptors in the ventrolateral striatum of SHR are hyposensitive
      when compared to those of WKY rats.

PMID- 14729385
TI  - Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic
      vasoconstriction.
AB  - The peripheral histamine H3 receptor is a presynaptic heterologous receptor
      located on postganglionic sympathetic nerve fibers innervating sympathetic
      effector systems such as blood vessels and the heart. An extensive body of
      evidence shows that activation of the histamine H3 receptor attenuates
      sympathetic tone by presynaptic inhibition of noradrenaline release. It is
      proposed that this sympathoinhibitory action, in vivo, leads to reduced
      vasoconstriction, thereby eliciting a vasodilatory effect. In humans, the
      peripheral histamine H3 receptor has also been shown to exert a
      sympathoinhibitory function on specific peripheral autonomic effector systems.
      For example, human saphenous vein and heart possess functional presynaptic
      histamine H3 receptors on the sympathetic nerve terminals that upon activation
      decrease the sympathetic tone to these respective organs. The present studies
      were conducted to define the role of histamine H3 receptors on neurogenic
      sympathetic vasoconstrictor responses in human nasal turbinate mucosa.
      Contractility studies were conducted to evaluate the effect of histamine H3
      receptor activation on sympathetic vasoconstriction in surgically isolated human
      nasal turbinate mucosa. We found that the histamine H3 receptor agonist, (R)
      alpha-methylhistamine (30 and 300 nM), inhibited electrical field stimulation
      induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent
      fashion. Pretreatment with the selective histamine H3 receptor antagonist,
      clobenpropit (100 nM), blocked the sympathoinhibitory effect of (R)-alpha
      methylhistamine on the neurogenic sympathetic vasoconstriction. In addition,
      analysis of Taqman mRNA expression studies showed a specific, high level of
      distribution of the histamine H3 receptor localized in the human nasal mucosa.
      Taken together, these studies indicate that histamine H3 receptors modulate
      vascular contractile responses in human nasal mucosa most likely by inhibiting
      noradrenaline release from sympathetic nerve terminals in nasal mucosa. It is
      further suggested that histamine H3 receptors may play a role in the regulation
      of vascular tone and nasal patency in histamine-dependent allergic nasal
      congestive disease.

PMID- 14729386
TI  - Homologous desensitization of calcitonin gene-related peptide-induced relaxation
      in rat intramural coronary arteries.
AB  - We investigated the type of desensitization of calcitonin gene-related peptide
      (CGRP)-induced responses in rat isolated intramural coronary arteries using
      isometric myograph and FURA-2 technique. In coronary arteries precontracted with
      9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha (U46619),
      development of tachyphylaxis to CGRP is characterized by significant attenuation
      of CGRP-induced maximal reduction in the tension and [Ca2+](i) during the second
      CGRP concentration-response curve; however, there was no further reduction in the
      CGRP-induced maximum relaxation during the third CGRP concentration-response
      curve. There was no sign of tachyphylaxis to CGRP when CGRP concentration
      response curves were recorded in 36 mM K+-depolarized coronary arteries contrary
      to the results obtained in 300 nM U46619-precontracted coronary arteries.
      Preincubation with colchicine did not prevent the development of tachyphylaxis to
      CGRP in U46619-precontracted coronary arteries, indicating no role for
      endocytosis. Development of tachyphylaxis to CGRP was completely abolished by
      preincubating the coronary arteries with 1 microM RO 31-8220, indicating a role
      for protein kinases. Pre-exposure of the coronary arteries to isoprenaline or
      forskolin did not attenuate the CGRP-induced relaxation in these vessels,
      indicating that the cAMP-protein kinase A (PKA) pathway is not involved. Like
      CGRP, the coronary arteries developed tachyphylaxis toward isoprenaline during
      the second exposure. However, there was no sign of tachyphylaxis to either
      forskolin or dibutyryl cAMP (dbcAMP) during the second exposure. In conclusion,
      these results suggest that development of tachyphylaxis to CGRP in U46619
      precontracted coronary is related to CGRP receptor-mediated activation of protein
      kinase.

PMID- 14729387
TI  - Ischemic heart disease induces upregulation of endothelin receptor mRNA in human
      coronary arteries.
AB  - Endothelin has been implicated in the pathogenesis of ischemic heart disease and
      congestive heart failure. The aims were to quantify endothelin type A (ETA) and
      type B (ETB) receptor mRNA levels in human coronary arteries from patients with
      ischemic heart disease, congestive heart failure and controls using real-time
      polymerase chain reaction (real-time PCR). In addition, the suitability of organ
      culture as a model mimicking endothelin receptor changes in cardiovascular
      disease was evaluated by in vitro pharmacology and real-time PCR. Endothelin ETA
      and ETB receptor mRNA levels were significantly higher in arteries from patients
      with ischemic heart disease (0.23+/-0.04 and 0.35+/-0.06) as compared to
      congestive heart failure (0.09+/-0.02 and 0.07+/-0.01) and controls (0.08+/-0.02
      and 0.08+/-0.01). After organ culture, the endothelin ETB receptor mRNA levels
      were elevated, and the sarafotoxin 6c-induced vasoconstriction was more
      efficacious. Increased endothelin receptor activity may contribute to the
      increased vascular tone and development of atherosclerotic disease in ischemic
      heart disease in man.

PMID- 14729388
TI  - Superoxide dismutase entrapped-liposomes restore the impaired endothelium
      dependent relaxation of resistance arteries in experimental diabetes.
AB  - Diabetes is associated with impaired endothelium-dependent relaxation. We
      questioned whether administration of superoxide dismutase (superoxide: superoxide
      oxidoreductase, EC 1.15.1.1) entrapped in long-circulating liposomes improves the
      vascular reactivity of the resistance arteries. Using the myograph technique, the
      vasodilation in response to acetylcholine was measured in mesenteric resistance
      arteries isolated from diabetic or normal hamsters treated for 3 days with
      superoxide dismutase entrapped in liposomes, with the same concentrations of free
      superoxide dismutase and plain liposomes, or untreated. Superoxide dismutase
      activity and nitric oxide (NO) levels were assayed by spectrophotometry,
      superoxide dismutase levels by Western blot and the role of N(pi)-nitro-L
      arginine ethylester (L-NAME) on vasodilation by the myograph technique. Our data
      revealed that: (i) superoxide dismutase entrapped in liposomes restored to a
      great extent the endothelium-dependent relaxation of diabetic hamster resistance
      arteries; (ii) in superoxide dismutase entrapped in liposomes-treated diabetic
      animals, the activity and the level of superoxide dismutase in arterial
      homogenates as well as the serum nitrite levels were significantly higher than
      those in untreated hamsters or hamsters treated with free superoxide dismutase
      and plain liposomes: (iii) L-NAME inhibited the response of arteries to
      acetylcholine in superoxide dismutase entrapped in liposomes-treated diabetic
      hamsters. These results suggest that superoxide dismutase entrapped in liposomes
      is effective in scavenging superoxide anions, increases nitric oxide bioactivity
      and improves the vasorelaxation of resistance arteries in diabetic hamsters.

PMID- 14729389
TI  - Genealogy, expression, and molecular mechanisms in apoptosis.
AB  - Apoptosis, known as programmed cell death, is a conserved, gene-directed
      mechanism for the elimination of unnecessary or unwanted cells from an organism.
      A retrospective look at the basis of human disease pathogenesis almost always
      reveals an apoptotic component that either contributes to disease progression or
      accounts for it. Modulating the expression of key molecular components of the
      cell death machinery is an attractive and obvious strategy for apoptosis-based
      therapeutics. Apoptosis is an important component of most developmental
      abnormalities and human diseases and in many cases the underlying cause of the
      resulting pathology. It has also become clear that many, if not all, viruses
      possess mechanisms to forestall apoptosis and provide a living host to enhance
      virus propagation. Diseases like AIDS involve excessive apoptosis, and
      suppression of apoptosis may restore functionality to the infected tissues.
      Although these are still early days, it is difficult not to get excited about the
      significant advances that have already been made. The true therapeutic benefits
      of apoptosis modulation for the treatment of many devastating human diseases
      remain to be discovered.

PMID- 14729390
TI  - Pharmacological modulation of cholesteryl ester transfer protein, a new
      therapeutic target in atherogenic dyslipidemia.
AB  - In mediating the transfer of cholesteryl esters (CE) from antiatherogenic high
      density lipoprotein (HDL) to proatherogenic apolipoprotein (apo)-B-containing
      lipoprotein particles (including very low density lipoprotein [VLDL], VLDL
      remnants, intermediate density lipoprotein [IDL], and low density lipoprotein
      [LDL]), the CE transfer protein (CETP) plays a critical role not only in the
      reverse cholesterol transport (RCT) pathway but also in the intravascular
      remodeling and recycling of HDL particles. Dyslipidemic states associated with
      premature atherosclerotic disease and high cardiovascular risk are characterized
      by a disequilibrium due to an excess of circulating concentrations of atherogenic
      lipoproteins relative to those of atheroprotective HDL, thereby favoring arterial
      cholesterol deposition and enhanced atherogenesis. In such states, CETP activity
      is elevated and contributes significantly to the cholesterol burden in
      atherogenic apoB-containing lipoproteins. In reducing the numbers of acceptor
      particles for HDL-derived CE, both statins (VLDL, VLDL remnants, IDL, and LDL)
      and fibrates (primarily VLDL and VLDL remnants) act to attenuate potentially
      proatherogenic CETP activity in dyslipidemic states; simultaneously, CE are
      preferentially retained in HDL and thereby contribute to elevation in HDL
      cholesterol content. Mutations in the CETP gene associated with CETP deficiency
      are characterized by high HDL-cholesterol levels (>60 mg/dL) and reduced
      cardiovascular risk. Such findings are consistent with studies of
      pharmacologically mediated inhibition of CETP in the rabbit, which argue strongly
      in favor of CETP inhibition as a valid therapeutic approach to delay
      atherogenesis. Consequently, new organic inhibitors of CETP are under development
      and present a potent tool for elevation of HDL in dyslipidemias involving low HDL
      levels and premature coronary artery disease, such as the dyslipidemia of type II
      diabetes and the metabolic syndrome. The results of clinical trials to evaluate
      the impact of CETP inhibition on premature atherosclerosis are eagerly awaited.

PMID- 14729391
TI  - Recent advances in the neurobiology of alcoholism: the role of adenosine.
AB  - Neuronal responses to alcohol involve several hormone- and neurotransmitter
      activated signal transduction pathways. Recent studies suggest that the adenosine
      A2 receptor (A2) mediates important actions of alcohol. Ethanol inhibits
      adenosine reuptake, increases extracellular adenosine, and promotes activation of
      A2. This leads to enhanced cAMP/protein kinase A (PKA) signaling ranging from
      increases in cAMP to stimulation of cAMP-dependent cAMP response element (CRE)
      mediated gene expression. Medium spiny neurons in the striatum/nucleus accumbens
      (NAc) express A2 and dopamine D2 receptor (D2) on the same cells. Studies in
      model neuronal cell lines and primary neurons in culture expressing A2 and D2
      provide evidence for synergy between ethanol/A2 and D2. Subthreshold
      concentrations of ethanol or a D2 agonist, without effect separately,
      synergistically activate cAMP/PKA signaling. Thus, neurons expressing A2 and D2
      on the same cells, like in the NAc, are characterized by hypersensitivity to
      ethanol with a simultaneous activation of dopaminergic signaling. Synergy
      requires adenosine and appears to be mediated by the release of free betagamma
      dimers from G(i/o) via D2 activation. The release of free betagamma has
      pathophysiological significance in the drinking animal because specific blockade
      of betagamma signaling in the NAc strikingly reduces voluntary alcohol
      consumption. These findings suggest that signaling pathways, which regulate
      synergy between A2 and D2, might contain molecular targets for the prevention and
      treatment of alcoholism and alcohol abuse.

PMID- 14729392
TI  - Nuclear inositides: facts and perspectives.
AB  - Strong evidence has been accumulating over the last 15 years suggesting that
      phosphoinositides, which are involved in the regulation of a large variety of
      cellular processes in the cytoplasm and in the plasma membrane, are present
      within the nucleus. Several advances have resulted in the discovery that nuclear
      phosphoinositides are involved in cell growth and differentiation. Remarkably,
      the nuclear inositide metabolism is regulated independently from that present
      elsewhere in the cell. Although nuclear inositol lipids generate second
      messengers such as diacylglycerol and inositol 1,4,5-trisphosphate, it is
      becoming increasingly clear that in the nucleus polyphosphoinositides may act by
      themselves to influence pre-mRNA splicing and chromatin structure. This review
      aims at highlighting the most significant and updated findings about inositol
      lipid metabolism in the nucleus.

PMID- 14729393
TI  - Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes.
AB  - The biological effects of epinephrine and norepinephrine are mediated via 9
      different adrenergic receptor subtypes, which all belong to the superfamily of G
      protein-coupled receptors. Although pharmacological ligands for adrenergic
      receptors have an important place in medical therapy, the full therapeutic
      potential of the 9 adrenergic receptor subtypes has not been explored yet. To
      dissect the physiological relevance of adrenergic receptor subtype diversity,
      gene-targeted mouse models carrying deletions in these receptor genes ("knockout
      mice") have been generated. This review gives an overview of the phenotypes
      observed in mice deficient in adrenergic receptors and discusses the therapeutic
      relevance of subtype-specific drug therapy.

PMID- 14729394
TI  - Mouse models to study G-protein-mediated signaling.
AB  - The G-protein-mediated signaling system has evolved as one of the most widely
      used transmembrane signaling mechanisms in eukaryotic organisms. Mammalian cells
      express many G-protein-coupled receptors as well as several types of
      heterotrimeric G-proteins and effectors. This review focuses on recent data from
      studies in mutant mice, which have elucidated some of the roles of G-protein
      mediated signaling in physiology and pathophysiology.

PMID- 14729395
TI  - Tachykinins and tachykinin receptors: a growing family.
AB  - The peptides of the tachykinin family are widely distributed within the mammalian
      peripheral and central nervous systems and play a well-recognized role as
      excitatory neurotransmitters. Currently, the concept that tachykinins act
      exclusively as neuropeptides is being challenged, since the best known members of
      the family, substance P, neurokinin A and neurokinin B, are also present in non
      neuronal cells and in non-innervated tissues. Moreover, the recently cloned
      mammalian tachykinins hemokinin-1 and endokinins are primarily expressed in non
      neuronal cells, suggesting a widespread distribution and important role for these
      peptides as intercellular signaling molecules. The biological actions of
      tachykinins are mediated through three types of receptors denoted NK(1), NK(2)
      and NK(3) that belong to the family of G protein-coupled receptors. The
      identification of additional tachykinins has reopened the debate of whether more
      tachykinin receptors exist. In this review, we summarize the current knowledge of
      tachykinins and their receptors.

PMID- 14729396
TI  - Structure-activity relationship of synthetic truncated analogues of vasoactive
      intestinal peptide (VIP): an enhancement in the activity by a substitution with
      arginine.
AB  - In order to develop potent shortened analogues of vasoactive intestinal peptide
      (VIP), the structure-activity relationship of C-terminally truncated analogues of
      VIP was investigated by examining the binding activity to rat lung VIP receptors
      and relaxation of smooth muscle in isolated mouse stomach. VIP(1-27) showed VIP
      receptor binding activity comparable to that of VIP but the activity of VIP(1-26)
      was reduced to one-third of VIP. The receptor binding activity of VIP(1-26) to
      VIP(1-23) was reduced in proportion to the decrease in amino acid residues. There
      was a significant correlation between the number of amino acid residues and VIP
      receptor binding activities of VIP and its C-terminally truncated analogues.
      VIP(1-22) and VIP(1-21) exhibited little binding activity even at high
      concentrations, suggesting the requisite of 23 amino acid residues as the minimal
      essential sequence for the conservation of VIP receptor binding activity. The
      chemical modification of VIP(1-23) generated a potent analogue, [Arg(15, 20, 21),
      Leu(17)]-VIP(1-23), that displayed a 22-fold higher receptor binding activity and
      1.6-fold more potent relaxation of mouse stomach than VIP(1-23) did. In
      conclusion, it was shown that [Arg(15, 20, 21), Leu(17)]-VIP(1-23) could be a
      relatively potent and stable agonist of VIP receptors. The present study has
      provided further insight into the structure-activity relationship of VIP to
      generate novel shortened VIP analogues having a high affinity to VIP receptors
      and potent pharmacological activity.

PMID- 14729397
TI  - Localization and variation of TRAIL and its receptors in human placenta during
      gestation.
AB  - The localization of TRAIL and its receptors in human placenta was studied under
      light microscopy using immunohistochemistry method. The variation of TRAIL and
      its receptors with development was also detected by in situ semi-quantification.
      The syncytiotrophoblast, cytotrophoblast, stromal cells and the capillary
      endothelium cells in human placenta all appeared to be TRAIL immunoreactive and
      the immunoreactive material was distributed on membrane and in cytoplasm with
      negative nuclei. During whole gestation there was no obvious variation of the
      staining of TRAIL. Although DR4, DR5, DcR1 and DcR2 can also be detected in the
      placenta throughout pregnancy, DR4 and DR5 staining increased with development
      whereas DcR1 and DcR2 staining decreased. Interestingly, at the beginning of the
      gestation DR4 and DR5 staining distributed on the cytotrophoblast mainly, whereas
      DcR1 and DcR2 mainly located in the syncytiotrophoblast cells. Collectively,
      these results suggest that human placenta may not only produce TRAIL but also be
      a TRAIL target organ, and that TRAIL/TRAILR system could take part in the self
      homeostasis of placenta during whole gestation.

PMID- 14729398
TI  - Chronic hypertriglyceridemia in young watanabe heritable hyperlipidemic rabbits
      impairs endothelial and medial smooth muscle function.
AB  - Several studies have suggested that hypertriglyceridemia is a common risk factor
      for coronary heart disease. Although increasing serum levels of triglyceride
      correlate with hypercoagulability, little is known about the contribution of
      hypertriglyceridemia to vascular function. We successfully segregated two lines
      of rabbits with genetically-determined severely high (TGH; 2764 +/- 413 mg/dl)
      and moderately high (TGL; 191 +/- 12 mg/dl) levels of triglyceride, but with
      comparable levels of total cholesterol, from Watanabe heritable hyperlipidemic
      rabbits. To determine whether hypertriglyceridemia was involved in alterations of
      vascular function, we conducted isometric tension studies and analyzed protein
      expression on thoracic aortic rings isolated from young (3-4 month) TGH, TGL and
      Japanese White rabbit (JW). No difference in percentage of plaque area in the
      thoracic aorta was found between TGH and TGL. Relaxing responses, evoked by
      sodium nitroprusside were similar in JW, TGL and TGH, but endothelium-dependent
      relaxation to acetylcholine was impaired in TGH compared with JW or TGL (maximal
      relaxation in JW; 83.5 +/- 2.7%, TGL; 79.9 +/- 5.3%, TGH; 59.1 +/- 5.7%, p<0.05).
      Relaxation to A23187 was also attenuated in TGH compared with JW, but not
      significantly different between TGL and JW. Endothelium-independent relaxation
      elicited by isoproterenol in TGH was significantly decreased compared with JW or
      TGL (maximal relaxation in JW; 95.2 +/- 2.6% TGL; 91.0 +/- 4.9%, TGH; 75.1 +/-
      5.2%, p<0.05). Protein expression of angiotensin II type-1 receptor was increased
      in TGH and that of nitric oxide synthases-3 was attenuated in TGH compared with
      TGL. This is the first study showing that endothelium-dependent and -independent
      vascular relaxation under the condition of combined hyperlipidemia was severely
      impaired as compared to that under only hypercholesterolemia. These results
      suggest that hypertriglyceridemia aggravates functional impairment induced by
      hypercholesterolemia in endothelial and smooth muscle cells.

PMID- 14729399
TI  - Tissue specific expression and immunohistochemical localization of glutathione S
      transferase in streptozotocin induced diabetic rats: modulation by Momordica
      charantia (karela) extract.
AB  - In streptozotocin (STZ)-induced diabetes, destruction of pancreatic beta-cell
      causes an acute shortage of insulin. Increased oxidative stress is believed to be
      one of the main factors in the etiology and complications of diabetes. In this
      study we have reported hyperglycemia and glutathione-associated oxidative stress
      in rats one week after treatment with STZ. In our previous studies, we have
      reported oxidative stress-related changes in xenobiotic metabolism in tissues
      from STZ-induced chronic diabetic rats. Here, we demonstrate by
      immunohistochemistry, that glutathione S-transferase (GST) isoenzymes are
      differentially expressed in the liver, kidney and testis of diabetic rats. The
      distribution of GST isoenzymes was found to be tissue- and regio-specific. In
      addition, we have also shown that treatment with an extract of Momordica
      charantia (karela), an antidiabetic herb, modulates GST expression in diabetic
      rats and reverts them to the normal distribution as seen in the tissues of
      control rats. These results suggest that glutathione metabolism and GST
      distribution in the tissues of diabetic rats may play an important role in the
      etiology, pathology and prevention of diabetes.

PMID- 14729400
TI  - Green tea metabolite EGCG protects membranes against oxidative damage in vitro.
AB  - Green tea polyphenols like epigallocatechin gallate (EGCG) have been proposed as
      a cancer chemopreventative. Several studies have shown that EGCG can act as an
      antioxidant by trapping proxyl radicals and inhibiting lipid peroxidation. The
      main propose of this study is to investigate the antioxidant capacity of EGCG
      using erythrocyte membrane-bound ATPases as a model. The effects of EGCG on t
      butylhydroperoxide-induced lipid peroxidation and the activity of membrane-bound
      ATPases in human erythrocyte membranes were studied. The extent of oxidative
      damage in membranes was assessed by measuring lipid peroxidation, (TBARS,
      thiobarbituric acid reactive substances formation) and the activity of ATPases
      (Na(+)/K(+), Ca(2+), and CaM-activated Ca(2+) pump ATPases). EGCG blocked t-BHP
      induced lipid peroxidation in erythrocyte membranes, significantly (0.45 +/- 0.02
      vs 0.20 +/- 0.01; t-BHP vs t-BHP + EGCG respectively, microm/L TBARS) (p < 0.05).
      EGCG also protected ATPases against t-BHP induced damage; for Na/K ATPase (2.4 +/
      0.2 vs 1.6 +/- 0.1 vs 2.44 +/- 0.2, nmol Pi/min/mg protein, control vs t-BHP vs
      t-BHP and EGCG respectively), for Ca ATPase (5.8 +/- 0.4 vs 3.9 +/- 0.3 vs 5.6 +/
      0.34, nmol Pi/min/mg protein, control vs t-BHP vs t-BHP and EGCG respectively)
      and for CaM-Ca ATPase (14.7 +/- 0.7 vs 7.3 +/- 0.4 vs 11.6 +/- 0.55, nmol
      Pi/min/mg protein, control vs t-BHP vs t-BHP and EGCG respectively) (p < 0.05).
      In conclusion our results indicate that EGCG is a powerful antioxidant that is
      capable protecting erythrocyte membrane-bound ATPases against oxidative stress.

PMID- 14729402
TI  - Maternal methamphetamine administration during pregnancy influences on fetal rat
      heart development. [corrected].
AB  - Methamphetamine (MAP) is one of the most abused drugs in Japan. The rate of MAP
      abuse by young women has recently reached more than 50 percent in adolescents. A
      major health concern is that these women will continue to use MAP during
      pregnancy. The purpose of this study was to investigate whether MAP administered
      to the mother during pregnancy would change the expression of alpha- and beta-
      myosin heavy chain (MHC) mRNA in rat neonatal hearts, as detected by quantitative
      RT-PCR. In addition, morphological changes in the rat neonatal ventricles were
      examined. Pregnant rats were injected intraperitoneally with MAP (1 mg/kg/day)
      starting at day 0 of gestation and ending at day 21. There was a significant
      increase in alpha-MHC mRNA expression in the neonatal ventricular muscle in the
      experimental group compared with the control at postnatal day (P) 0 and 5. alpha
      MHC mRNA expression in both groups was similar after P9. beta-MHC mRNA expression
      was similar in both groups at P0. Postnatal beta-MHC mRNA expression decreased
      rapidly, but significant alteration was not detected. Neonatal rats at P0
      exhibited some cardiac changes, including hypertrophy, degeneration, and
      disarrangement of myofibers, but these lesions disappeared by P14. We conclude
      that chronic maternal administration of MAP changes the alpha- and beta-MHC mRNA
      expression pattern in fetal and neonatal hearts, correlating with abnormal
      development, plasma level of hormones, and myocardial damage. At the same time,
      it is indicated that neonatal cardiomyocytes have reversibility.

PMID- 14729401
TI  - Postnatal changes in gene expression of retinal dehydrogenase and retinoid
      receptors in liver of rats.
AB  - Retinoic acid (RA) plays important roles in cellular differentiation and
      proliferation in various tissues including the liver. To explore a possible role
      of RA in the postnatal development of hepatic function, we analyzed RA-generation
      enzyme activity and the RA-related hepatic gene expressions in the suckling and
      weaning rats. At 5 days after birth, retinal dehydrogenase (RALDH) activity in
      the liver was relatively high. Its activity decreased by 70% until day 17, and
      then it gradually increased to a high level by the completion of weaning period.
      Northern blot analysis showed that RALDH2 mRNA levels decreased in the suckling
      period, whereas RALDH1 mRNA levels increased in the weaning period. Retinoid X
      receptor alpha (RXRalpha) mRNA levels increased in the suckling period and
      attained to a higher level at 17 days after birth. Retinoic acid receptor alpha
      (RARalpha) mRNA level showed only a slight and temporary increase on day 13. The
      mRNA levels of hepatocyte nuclear factors (HNF-4 and HNF-1alpha) exhibited
      parallel increases around suckling-weaning period, and the transcript levels of
      albumin, a typical target gene of the hepatocyte nuclear factors, increased
      during the suckling-weaning transition period. Electrophoretic mobility shift
      assay using a putative nuclear receptor-binding element on rat HNF-1 alpha gene
      revealed that HNF-4 homodimer, but not RXRalpha homodimer, bound to this element.
      These results suggest that postnatal expressions of hepatocyte-specific genes
      might be up-regulated by retinoid receptors, which may be related with the
      alterations of RALDH expression during postnatal development in the liver.

PMID- 14729403
TI  - Selective and transient activation of protein kinase C alpha by fumonisin B1, a
      ceramide synthase inhibitor mycotoxin, in cultured porcine renal cells.
AB  - Fumonisin B(1) (FB(1)), a potent and naturally occurring mycotoxin produced by
      the fungus Fusarium verticillioides, has been implicated in fatal and
      debilitating diseases in animals and humans. FB(1) affects a variety of cell
      signaling proteins including protein kinase C (PKC); a serine/threonine kinase,
      involved in a number of signal transduction pathways that include cytokine
      induction, carcinogenesis and apoptosis. The aim of this study was to investigate
      the short-term temporal and concentration-dependent effects of FB(1) on PKC
      isoforms present in LLC-PK(1) cells in relation to the FB(1)-induced accumulation
      of sphinganine and sphingosine utilizing various inhibitors and activators. Our
      studies demonstrated that FB(1) (0.1-1 microM) selectively and transiently
      activated PKCalpha at 5 min, without affecting PKC-delta, -epsilon and -zeta
      isoforms. At higher FB(1) concentrations and later time points (15-120 min),
      PKCalpha membrane concentrations declined to untreated levels. The observed
      increase in cytosol PKCalpha protein expression at 15 min was not associated with
      an increase in its activity or protein biosynthesis. Calphostin C, a PKC
      inhibitor, abrogated the FB(1)-induced translocation of PKCalpha. Pre-incubation
      with the PKC activator, phorbol 12-myristate 13-acetate, resulted in an additive
      effect on membrane translocation of PKCalpha. Intracellular sphinganine and
      sphingosine concentrations were unaltered at the time points tested. Myriocin, a
      specific inhibitor of serine palmitoyltransferase, the first enzyme in de novo
      sphingolipid biosynthesis, did not prevent the FB(1)-induced PKCalpha cytosol to
      membrane redistribution. Altering PKCalpha and its signal transduction pathways
      may be of importance in the ability of FB(1) to exert its toxicity via apoptosis
      and/or carcinogenesis.

PMID- 14729404
TI  - Temporal changes in matrix metalloproteinase expression and inflammatory response
      associated with cardiac rupture after myocardial infarction in mice.
AB  - We previously found that male mice with myocardial infarction (MI) had a high
      rate of cardiac rupture, which generally occurred at 3 to 5 days after MI. Since
      matrix metalloproteinases (MMPs) play an important role in infarct healing,
      tissue repair and extracellular matrix (ECM) remodeling post-MI, we studied the
      temporal relationship of MMP expression and inflammatory response to cardiac
      rupture after acute MI. Male C57BL/6J mice were subjected to MI (induced by
      ligating the left anterior descending coronary artery) and killed 1, 2, 4, 7 or
      14 days after MI. MMP-2 and MMP-9 activity in the heart were measured by
      zymography. Collagen content was measured by hydroxyproline assay. We found that
      after MI, MMP-9 activity increased as early as 1 day and reached a maximum by 2-4
      days, associated with a similar increase in neutrophil and macrophage
      infiltration in the infarct area. MMP-2 started to increase rapidly within 4
      days, reaching a maximum by 7 days and remaining high even at 14 days. Intense
      macrophage infiltration appeared by 4 days after MI and then gradually decreased
      within 7 to 14 days. Collagen content was unchanged until 4 days after MI, at
      which point it increased and remained high thereafter. Our data suggest that in
      mice, overexpression of MMP-2 and MMP-9 (possibly expressed mainly by neutrophils
      and macrophages) may lead to excessive ECM degradation in the early phase of MI,
      impairing infarct healing and aggravating early remodeling which in turn causes
      cardiac rupture.

PMID- 14729405
TI  - Founders of Child Neurology in Japan - Yukio Fukuyama.

PMID- 14729406
TI  - Gastrin-releasing peptide receptor (GRPR) locus in Japanese subjects with autism.
AB  - Gastrin-releasing peptide receptor (GRPR) gene is considered a candidate locus
      for infantile autism for several reasons. The present study investigated two
      polymorphic sites (C/450/T and C/661/T) in the second exon of the GRPR gene in
      Japanese patients with autism (DSM-IV) and healthy subjects. The two polymorphic
      sites were at high linkage disequilirium, consistent with a previous study in a
      North American population. The C450-C661 allele, which was observed in one-third
      of the chromosomes from the North American subjects, was less frequent (6-7%) in
      the Japanese subjects, suggesting a large ethnic difference in the frequency of
      the polymorphism. The allele frequencies and genotype distributions were not
      significantly different between the patients and controls. However, further
      studies are required to exclude the GRPR locus as a candidate locus for autism,
      considering the low frequency of the polymorphism in the Japanese subjects.

PMID- 14729407
TI  - F-waves in neonates: increased spinal anterior horn motor neuron excitability.
AB  - We analyzed characteristics of F-waves in neonates to establish normal parameters
      for this age. F-waves recorded from the median nerve in 26 normal neonates were
      analyzed and compared to those in 10 adults. F-wave parameters measured included
      occurrence rate (Fpersistence), latency (Flatency), latency corrected for subject
      height (normalized Flatency), duration (Fduration), amplitude (Famplitude) and
      its ratio to M-wave amplitude (F/M ratio), F-wave conduction velocity (FCV), and
      Fchronodispersion. Mean Fpersistence in neonates was 100%. Famplitude and the F/M
      ratio were higher in neonates than in adults. Similar F-wave waveforms were
      observed repeatedly in neonates, while waveforms varied in adults. These results
      in neonates suggest increased excitability of motor neurons in the spinal
      anterior horn reflecting immaturity of inhibition by the central nervous system.

PMID- 14729408
TI  - 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: impaired catabolism of
      isoleucine presenting as neurodegenerative disease.
AB  - We describe a further case of recently reported 2-methyl-3-hydroxybutyryl-CoA
      dehydrogenase (MHBD) deficiency, a disorder of isoleucine metabolism. The
      development of pronounced brain atrophy and symmetrical alterations of the basal
      ganglia were observed and the importance of specific enzymatic tests is
      emphasized, which should be performed if urinary metabolites suggest impaired
      catabolism of isoleucine.

PMID- 14729410
TI  - Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic
      localization-related epilepsies.
AB  - The purpose of this study was to clarify the risk factors of relapse following
      discontinuation of AEDs in patients with childhood-onset cryptogenic localization
      related epilepsies. The subjects were 82 patients who fulfilled the following
      criteria: (1) age at first visit of less than 15 years, (2) follow-up period of
      more than 5 years, (3) suffering from cryptogenic localization-related
      epilepsies, and (4) the patient underwent AED withdrawal during the follow-up
      period. As a basic principle, we decided to start withdrawing AEDs when both of
      the following two conditions were met: (1) the patient had a seizure-free period
      of 3 years or more, and (2) there were no epileptic discharges on EEGs just prior
      to the start of withdrawal. Seizures recurred in eight of the 82 patients (9.8%).
      Univariate analysis revealed that the following factors were correlated with
      higher rates of seizure relapse: 6 years of age or higher at onset of epilepsy;
      15 years of age or higher at the start of AED withdrawal; 5 years or more from
      the start of AED treatment to seizure control; five or more seizures before
      seizure control; and two or more AEDs administered before seizure control. Among
      these risk factors, 6 years of age or higher at onset and 5 years or more from
      the start of AED treatment to seizure control were determined by multivariate
      analysis to be independent risk factors for relapse. Thus, we conclude that the
      physician should be more careful in discontinuing AEDs in these higher-risk
      patients groups, and more generous in discontinuing AEDs in lower-risk groups.

PMID- 14729409
TI  - Serum nitrite and nitrate levels in epileptic children using valproic acid or
      carbamazepine.
AB  - In experimental epilepsy studies, nitric oxide was found to act as both
      proconvulsant and anticonvulsant. The objective of this study was to investigate
      the effects of valproic acid and carbamazepine on serum levels of nitrite and
      nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum
      nitrite and nitrate levels were determined in active epileptic 34 children using
      valproic acid and 23 children using carbamazepine and in non-active epileptic 38
      children (control group) not using any antiepileptic drug. In the valproic acid
      group serum nitrite and nitrate levels were 2.66 +/- 2.11 micromol/l and 69.35 +/
      23.20 micromol/l, 1.89 +/- 1.01 micromol/l and 49.39 +/- 10.61 micromol/l in the
      carbamazepine group, and 1.22 +/- 0.55 micromol/l, 29.53 +/- 10.05 micromol in
      the control group, respectively. Nitrite and nitrate levels were significantly
      high in both valproic acid and carbamazepine groups compared to the control group
      (P < 0.01). When valproic acid and carbamazepine groups were compared to each
      other, level of nitrate was found statistically higher in the valproic acid group
      in relation to the carbamazepine group (P < 0.01), however, there was no
      statistically significant difference in the levels of nitrite (P > 0.05). No
      relation could be found between serum drug levels and nitrite and nitrate levels.
      According to these results, it can be suggested that valproic acid and
      carbamazepine might have antiepileptic effects through nitric oxide.

PMID- 14729411
TI  - Lamotrigine as first-line drug in childhood absence epilepsy: a clinical and
      neurophysiological study.
AB  - To investigate to which extent lamotrigine (LTG) may be effective and tolerated
      as a monotherapy for the treatment of newly diagnosed childhood absence seizures
      and, secondly, to evaluate the efficacy of this drug on the circadian interictal
      generalized epileptiform discharges, 20 consecutive newly diagnosed patients
      (five males, 15 females), aged 3-10 years (mean 6.9 years), affected by childhood
      absence epilepsy, were administered LTG as first-line drug at the initial dose of
      0.5 mg/kg/day for 2 weeks, followed by 1.0 mg/kg/day for an additional 2 weeks.
      Thereafter, doses have been increased in 1-mg/kg/day increments up to 9-12
      mg/kg/day in accordance with the clinical response. Each patient underwent an
      ambulatory (24 h) EEG monitoring before starting LTG therapy (time 0) and during
      the maintenance period at the end of LTG titration (time 1). After a mean follow
      up period of 10.8 months (range 3-28 months), a 100% seizure control was obtained
      in 11 children (55.5%), a more than 75% seizure decrease was present in four
      (20%), and a >50% seizure decrease in five (25%), with a mean LTG dose of 6.2
      mg/kg/day (range 1.2-11) in the controlled group. Adverse events were present in
      three patients (15%); they were generally mild and transient. Our series confirms
      that LTG monotherapy may control typical childhood absence seizures in about half
      the children as well as it may decrease interictal generalized spike and wave
      discharges both in seizure-free and uncontrolled patients. The slow titration
      phase of the drug due to the risk of the skin rash may eventually reduce
      compliance.

PMID- 14729412
TI  - Human brain of preterm infants after hypoxic-ischaemic injuries: no evidence of a
      substantial role for apoptosis by using a fine-tuned ultrasound-guided
      neuropathological analysis.
AB  - Preterm birth may be associated with hypoxic-ischaemic encephalopathy (HIE)
      showing a well recognised number of patterns, including neuronal
      karyorrhexis/eosinophilia mostly at the diencephalon and brain stem and
      leukomalacia at the periventricular white matter. To investigate whether
      programmed cell death or apoptosis plays a role in HIE, we examined human brains
      of preterm infants. Brain tissue samples from 12 consecutive infants (24-34 weeks
      of gestation) were available at post-mortem examination (1998-2000) after
      approval of the Ethics Committee. Two tissue sections were stereologically
      localised after brain fixation, slice preparation, and comparison with ultrasound
      imaging. We studied the periventricular white matter and the corresponding
      cortical region in each brain. Conventional histological stains were used. In
      addition, apoptosis was detected using a neuronal-specific terminal
      deoxynucleotidyl transferase-mediated nick end-labelling (TUNEL) method
      (NeuroTACS). A semiquantitative evaluation was performed to compare regions close
      to brain lesions with injury-free areas. Neuronal apoptosis was low in both
      cortical and in periventricular regions. No glial apoptosis was detected.
      Apoptosis in neurones was, however, detected in preterm brains with bacterial or
      mycotic infection. These results point out to the ambiguity of the TUNEL-reactive
      neurons in the diseased premature infants using fine-tuned ultrasound-guided
      neuropathological analysis, support the probable coexistence of neuronal TUNEL
      reactivity and infection, and suggest that the association between apoptosis and
      HIE should overall be viewed with more caution.

PMID- 14729413
TI  - Context-dependent reasoning in a cognitive bias task Part II. SPECT activation
      study.
AB  - A cognitive bias task (CBT) delineates two different cognitive selection
      mechanisms in the prefrontal cortex. To identify functional anatomy of context
      dependent reasoning, we used technetium-99mhexamethyl- propyleneamine oxime
      (99mTc HM-PAO) single photon emission computed tomography (SPECT) and statistical
      parametric mapping. Twelve right-handed men 20-24 years old were instructed to
      look at a target card and then select the choice card (among two) that they
      preferred (modified CBT; mCBT). They also selected a choice card 2 weeks later
      without prior presentation of a target card (control task). In both tasks, 99mTc
      HM-PAO was injected intravenously about 15 s after initiation of the mCBT or
      control task. Brain images were obtained using a gamma camera and reconstructed
      by a UNIX-based workstation. Statistical analysis compared all activated images
      to control images. Results associated with P values of less than 0.01 (Z score >
      2.36) were depicted on T1-weighted magnetic resonance images. All subjects
      preferred choices more similar to the target. SPECT activation occurred
      bilaterally in the dorsolateral prefrontal cortices and middle temporal gyri
      during performance of the CBT. Additionally, the left inferior prefrontal cortex
      and left fusiform gyrus showed significant activation compared with the control
      task. A neural network linking the temporal and prefrontal cortices prominently
      seen in the left hemisphere participates in context-dependent reasoning.
      Knowledge of such neural systems is essential for understanding prefrontal lobe
      function and dysfunction.

PMID- 14729414
TI  - Hypouricemia in severely disabled children II: influence of elemental enteral
      nutrition on the serum uric acid levels.
AB  - The previous study showed that both valproic acid (VPA) and a bedridden state
      decreased the serum uric acid level, and VPA-induced renal tubular dysfunction
      was suspected to be one cause of hypouricemia in severely disabled children.
      However, it was uncertain what factor of bedridden state influences the uric acid
      level in severely disabled children. Among many factors of a bedridden state that
      might influence the uric acid level, we examined the influence of elemental
      nutrition on the serum uric acid level in severely disabled children because many
      severely disabled children with marked hypouricemia receive elemental nutrition.
      Thirty-one severely disabled children were included in this study, who were
      divided into two groups-group A: 11 patients with elemental nutrition; group B:
      20 patients with non-elemental nutrition. The laboratory data in both groups were
      analyzed statistically, using the t-test. The uric acid level was significantly
      decreased in group A compared with group B (p < 0.01) without elevation of
      urinary excretion of uric acid. Other laboratory data, except phosphate and
      potassium, did not differ between the two groups significantly. An elemental diet
      may be one factor that decreases the uric acid level in severely disabled
      children.

PMID- 14729415
TI  - Clinical and neurophysiological characteristics of congenital myasthenic
      syndromes presenting in early infancy.
AB  - The congenital myasthenic syndromes (CMS) constitute a group of genetic
      disorders, which affect neuromuscular transmission, presenting usually within the
      first years of life and with a clinical spectrum ranging from mild muscle
      weakness to severe disability with life-threatening episodes. We present clinical
      and neurophysiological data of 11 patients (four males, seven females) with CMS
      diagnosed during the last 5 years. Eight of the 11 patients presented immediately
      after birth and the remainder by 10 months of age; eight patients had
      contractures at birth and seven of them required assisted ventilation either
      immediately in the neonatal period, or at some point afterwards due to
      respiratory distress or recurrent apnoeas. Neurological signs at presentation
      were: in nine patients profound hypotonia, in five absent tendon reflexes, in
      seven ptosis and in eight bulbar signs. In six patients an edrophonium test was
      performed: only three of them had a positive response; however, eight out of 11
      patients responded at least partially at some point in their illness to
      pyridostigmine. Diagnosis of CMS was confirmed either by demonstration of a
      decrement after repetitive nerve stimulation or by increased instability and
      jitter after stimulated single fibre EMG. In five patients, there was a positive
      family history with death of at least one previous sibling with an undiagnosed
      neuromuscular disorder. As regards final outcome, five patients died at ages
      ranging from 1 to 17 months, two patients are still ventilator-dependent at 3 and
      5 months of life, respectively, and four patients still survive with either a
      mild or a moderate motor delay (follow-up range 8-38 months). None of the
      clinical or neurophysiological characteristics were correlated with outcome
      (Fisher's exact test). We conclude that a significant number of CMS patients may
      present in the neonatal period with a variable clinical expression and usually
      with a poor prognosis. The recognition of specific clinical constellations
      combined with a search for aetiology at a molecular level will enable the further
      characterisation of subgroups of CMS.

PMID- 14729416
TI  - Thalamic lesions in a long-surviving child with spinal muscular atrophy type I:
      MRI and EEG findings.
AB  - Brain magnetic resonance imaging was conducted in a girl with genetically
      confirmed spinal muscular atrophy (SMA) type I. This patient has survived 6
      years, to date, under mechanical ventilation. T2-weighted and fluid-attenuated
      inversion recovery images revealed high signal intensity lesions in the
      anterolateral portions of the bilateral thalami. Electroencephalography disclosed
      diffuse beta activity upon awakening and during light sleep. In addition, fast
      and prolonged spindles were observed. Although mild neuronal changes in the
      lateral nucleus of the thalamus have been described in several autopsied cases,
      this is the first study to demonstrate neuroradiologically and
      neurophysiologically the thalamic lesions in genetically confirmed SMA type I.

PMID- 14729417
TI  - Pyruvate dehydrogenase E1alpha subunit deficiency in a female patient: evidence
      of antenatal origin of brain damage and possible etiology of infantile spasms.
AB  - Enlargement of the lateral ventricles and atrophy of the brain were documented
      ultrasonographically in utero at as early as 28th week of gestation in a female
      patient with lactic acidosis due to deficiency of the pyruvate dehydrogenase
      E1alpha subunit, demonstrating that the changes characteristic of this disease
      can occur antenatally. The mechanism of infantile spasms in this disease may be
      linked to mosaicism of the brain cells involving the normal enzyme and the mutant
      enzyme.

PMID- 14729418
TI  - Pediatric hypothalamic lipoma with hypothermia--case report.
AB  - This case report describes a lipoma located in the pre-mamillary area that
      appeared in a 5-year-old child. The first symptom was very deep, transient
      hypothermia. Laboratory exams were normal. Diagnosis of a lipoma situated in the
      hypothalamic-mamillary area was made by brain MRI. The lipoma showed no signs of
      growth and hypothermia disappeared over the following 2 years. It is an unusual
      case of the body adapting to a new anatomic situation.

PMID- 14729419
TI  - Unusual side-effects due to clobazam: a case report with genetic study of
      CYP2C19.
AB  - We describe the case of a 10-year-old girl with two epileptic seizures and
      subcontinuous spike-waves during sleep, who presented unusual side-effects
      related to clobazam (CLB) monotherapy. High plasma levels of N-desmethyl-clobazam
      (N-CLB), the major metabolite of CLB were detected. The patient and her parents
      underwent molecular analysis of the CYP2C19 gene, which may be implicated in the
      metabolism of this drug. Our patient presents one copy of the most common
      mutation (CYP2C19*2) affecting the activity of the isoenzyme and probably another
      rare or private mutation. CLB and N-CLB plasma level dosages and molecular
      analysis may be useful when a poor metabolic condition is suspected.

PMID- 14729421
TI  - Attentional biases in eating disorders: a meta-analytic review of Stroop
      performance.
AB  - The Stroop task has been adapted from cognitive psychology to be able to examine
      attentional biases in various forms of psychopathology, including the eating
      disorders. This paper reviews the research on the Stroop task in the eating
      disorders research area in both descriptive and meta-analytic fashions. Twenty
      eight empirical studies are identified, which predominantly examine food and
      body/weight stimuli in bulimic, anorexic, or dieting/food-restricted samples. It
      is concluded that there is evidence of an attentional bias in bulimia for a range
      of stimuli but that the effect seems to be limited to body/weight stimuli in
      anorexia. The evidence to date is that there is no attentional bias in dieting
      samples. Limitations of the methodology employed in the extant literature include
      small sample sizes, unstandardized Stroop methodology, restricted gender, and a
      general lack of consideration of individual differences variables.
      Recommendations for future research are provided.

PMID- 14729422
TI  - Does batterers' treatment work? A meta-analytic review of domestic violence
      treatment.
AB  - This meta-analytic review examines the findings of 22 studies evaluating
      treatment efficacy for domestically violent males. The outcome literature of
      controlled quasi-experimental and experimental studies was reviewed to test the
      relative impact of Duluth model, cognitive-behavioral therapy (CBT), and other
      types of treatment on subsequent recidivism of violence. Study design and type of
      treatment were tested as moderators. Treatment design tended to have a small
      influence on effect size. There were no differences in effect sizes in comparing
      Duluth model vs. CBT-type interventions. Overall, effects due to treatment were
      in the small range, meaning that the current interventions have a minimal impact
      on reducing recidivism beyond the effect of being arrested. Analogies to
      treatment for other populations are presented for comparison. Implications for
      policy decisions and future research are discussed.

PMID- 14729423
TI  - The five-factor model and personality disorder empirical literature: A meta
      analytic review.
AB  - The current meta-analysis reviews research examining the relationships between
      each of the five-factor model personality dimensions and each of the 10
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      personality disorder diagnostic categories. Effect sizes representing the
      relationships between these two constructs were compiled from 15 independent
      samples. Results were analyzed both within each individual personality disorder
      category and across personality disorders, indicating how personality disorders
      are different and similar, respectively, with regard to underlying personality
      traits. In terms of how personality disorders differ, the results showed that
      each disorder displays a five-factor model profile that is meaningful and
      predictable given its unique diagnostic criteria. With regard to their
      similarities, the findings revealed that the most prominent and consistent
      personality dimensions underlying a large number of the personality disorders are
      positive associations with Neuroticism and negative associations with
      Agreeableness. Extraversion appears to be a more discriminating dimension, as
      indicated by prominent but directionally variable associations with the
      personality disorders. The implications of these meta-analytic findings for
      clinical application and the advancement of future research are discussed.

PMID- 14729424
TI  - Role of culture in gambling and problem gambling.
AB  - There has been a significant gap in the gambling literature regarding the role of
      culture in gambling and problem gambling (PG). This paper aims to this such gap
      by presenting a systematic review of the cultural variations in gambling and PG
      as well as a discussion of the role cultural variables can play in the initiation
      and maintenance of gambling in order to stimulate further research. The review
      shows that although studies investigating prevalence rates of gambling and PG
      among different cultures are not plentiful, evidence does suggest certain
      cultural groups are more vulnerable to begin gambling and to develop PG.
      Significant factors including familial/genetic, sociological, and individual
      factors have been found in the Western gambling literature as playing important
      roles in the development and maintenance of PG. These factors need to be examined
      now in other cultural groups so we can better understand the etiological
      processes involved in PG and design culturally sensitive treatments. In addition,
      variables, such as cultural values and beliefs, the process of acculturation, and
      the influence of culturally determined, help-seeking behaviors need to be also
      examined in relation to the role they could play in the initiation of and
      maintenance of gambling. Understanding the contribution of cultural variables
      will allow us to devise better prevention and treatment options for PG.
      Methodological problems in this area of research are highlighted, and suggestions
      for future research are included.

PMID- 14729425
TI  - Treatment motivation: An attempt for clarification of an ambiguous concept.
AB  - Although the concept of treatment motivation is generally regarded as highly
      relevant, it has since long been surrounded by conceptual confusion, resulting in
      miscommunication, ambiguous measures, and contradictory conclusions of research.
      This article provides an analysis of three major sources of confusion in the
      conceptualization of treatment motivation: (a) negligence of the concepts'
      intrinsic relationship with behavior, (b) entanglement of the concept with its
      determining factors and behavioral consequences, and (c) conceptualization in a
      stage model. Following the conceptual analysis, causes of the problems and
      implications for clinical praxis and research are considered. Finally, a more
      adequate conceptualization of treatment motivation is proposed and suggestions
      for future research are made.

PMID- 14729426
TI  - Understanding marriage and stress: essential questions and challenges.
AB  - This paper explores the complex interplay between stressors and marital
      functioning, beginning with a discussion of how key concepts from the stress and
      coping literature can be extended to the study of dyads. Five essential questions
      are outlined as a means of advancing research in this domain, addressing
      protective dyadic processes, the competing demands of individual and dyadic
      coping agendas, the role of individual well-being in couples' stress and coping,
      stress in the broader context of couples' lives, and prospects for intervention.
      Following an overview of methodological and procedural challenges, the paper
      concludes by noting that research devoted to understanding marriages in the
      context of stress is at a crossroads, poised between a set of provocative
      questions, preliminary findings, and intervention possibilities on one hand, and
      important theoretical and empirical challenges on the other.

PMID- 14729427
TI  - Efficacy and safety of endovascular intracoronary brachytherapy.
AB  - Intracoronary brachytherapy has emerged as one of the novel exciting developments
      in the field of interventional cardiology to counteract the problem of
      restenosis. Restenosis is the major limitation to a full expansion of all
      revascularization procedures. Elastic recoil, unfavorable remodeling and a
      proliferative response to injury are the more importune mechanisms to restenosis.
      The technique of intracoronary brachytherapy involves application of locally
      delivered radiation or brachytherapy in the management of restenosis. Ionizing
      radiation has been shown to decrease the proliferative response to injury in
      animal models of restenosis. Subsequently, several small randomized trials have
      demonstrated that intracoronary brachytherapy can reduce the rates of both
      angiographic and clinical restenosis in patients undergoing percutaneous coronary
      intervention for in-stent restenosis.

PMID- 14729428
TI  - Electrophysiological changes following balloon valvuloplasty and angioplasty for
      aortic stenosis and coartaction of aorta: clinical evidence for mechano
      electrical feedback in humans.
AB  - BACKGROUND: Basic research and animal experiments have shown electrophysiological
      changes during or after changes in mechanical loading. Electrical instability
      following mechanical stretch has been observed as development of after
      depolarisation and dispersion of refractoriness and repolarisation. The aim of
      the present study was to evaluate the presence of the mechano-electrical feedback
      in humans, assessing the ventricular repolarisation changes following acute
      changes in left ventricular pressure. MATERIAL AND METHODS: The study group
      comprised 30 consecutive patients (22 M and 8 F, aged 2 days-24 years) affected
      by severe congenital aortic stenosis and 30 patients (20 M and 10 F, aged 6
      months-16 years) affected by severe coartaction of aorta. Ventricular
      repolarisation was evaluated before and after percutaneous balloon valvuloplasty
      and angioplasty in terms of absolute measures (JT, JTc, QT, QTc) and in terms of
      dispersion across the myocardium: QT and QTc dispersion (QTD, QTcD), JT and JTc
      dispersion (JTD and JTcD) and T-peak to T-end interval (Tp-Te). RESULTS: Patients
      with severe aortic stenosis and patients with aortic coartaction showed a
      significant decrease in dispersion of ventricular repolarisation time indexes
      (QTD, QTcD, JTD, JTcD and Tp-Te) following valvuloplasty and angioplasty.
      CONCLUSIONS: Changes in hemodynamic loading can also produce electrophysiological
      effects in humans. Acute reduction in left ventricular pressure overload
      following balloon valvuloplasty and angioplasty, decreases electrical
      instability, as expressed by the reduction across the myocardium of the
      dispersion of ventricular repolarisation.

PMID- 14729429
TI  - Increase in soluble E-selectin level after PTCA and stent implantation: a
      potential marker of restenosis.
AB  - BACKGROUND: E-Selectin is expressed only on activated endothelial cells, and may
      be used as a marker of endothelial activation. The relationship between soluble
      form of E-selectin (sE-selectin) and development of restenosis after balloon
      angioplasty (PTCA) is controversial, and there are no data for after stent
      implantation. We evaluated the role of serially measured sE-selectin levels in
      predicting the development of restenosis after PTCA and stent implantation.
      METHODS: In sixty-one patients with stable angina pectoris who underwent PTCA
      (n=20) or stent implantation (n=41), peripheral blood samples were taken just
      before (baseline), at 3 and at 24 h after the intervention. sE-Selectin levels
      were measured by ELISA. Coronary angiography was repeated at 4-6 months after the
      intervention, and > or =50% stenosis at the site of the intervention was regarded
      as restenosis. Levels and time course of sE-selectin after the intervention were
      compared in patients with and those without restenosis. RESULTS: sE-Selectin
      levels of the patients with and those without restenosis were similar at each of
      the three measurements, and significantly increased after the intervention both
      in the PTCA and stent groups (P<0.001 for both groups). Posthoc analysis showed
      that sE-selectin levels increased significantly at 3 h after PTCA (P=0.024) and
      stent implantation (P=0.018), and did not change thereafter in patients with
      restenosis. In the nonrestenotic group, sE-selectin did not change significantly
      in the 24 h following PTCA, however, a significant difference was observed only
      by comparing the values at baseline with those at 24 h after stent implantation
      (P=0.021). CONCLUSIONS: A substantial increase in sE-selectin levels early (at 3
      h) after PTCA and stent implantation may predict development of restenosis.

PMID- 14729430
TI  - Thymoquinone and Nigella sativa oil protection against methionine-induced
      hyperhomocysteinemia in rats.
AB  - Although the state of hyperhomocysteinemia (HHcy) appears to be associated with
      higher risks of coronary, cerebral and peripheral vascular disease as well as
      with a number of other clinical conditions, the underlying molecular mechanisms
      are not fully elucidated. There is strong evidence, however, that HHcy could
      induce a pathogenic state of oxidative stress. The interest in modulating the
      elevated levels of total homocysteine in HHcy and/or their negative impacts
      through preventive strategies, particularly through the supplementation with
      vitamins that may be linked to the homeostasis of homocysteine (folate, vitamin
      B(12), and vitamin B(6)), has increased in recent years. Here we show that active
      antioxidant components of the traditionally used black seeds of Nigella sativa
      plant protect against the development of methionine-induced HHcy and its
      associated state of oxidative stress. Pretreatment of rats with an oral dose of
      100 mg/kg of thymoquinone, the main active constituent of the black seed, for 30
      min and for 1 week almost completely protected against induced HHcy measured 5 h
      after methionine load (100 mg/kg). Under similar conditions pretreatment with
      commercial black seed oil (100 microl/kg) for 30 min and for 1 week produced
      significant and strong protection levels of 74.2 and 94.5%, respectively. Under
      the state of induced HHcy there were significant increases in the plasma levels
      of triglycerides, lipid peroxidation, cholesterol and in the activities of
      glutathione peroxidase and superoxide dismutase. Catalase activity was not
      affected. The total antioxidant status, however, was significantly depressed. All
      of these effects were almost totally blocked by prior treatment with thymoquinone
      or black seed oil. These findings may contribute towards a protective measure
      utilizing the black seed against the negative impacts of HHcy.

PMID- 14729431
TI  - Chlamydia pneumoniae and future risk in patients with coronary heart disease.
AB  - AIM: To evaluate the association between previous exposure to Chlamydia
      pneumoniae and future coronary risk in patients with coronary heart disease.
      METHODS: A prospective, nested, case-control design was used. The patient sample
      was derived from a trial study of bezafibrate for the treatment of coronary heart
      disease. Anti-Chlamydia pneumoniae antibodies (IgG and IgA) in the baseline sera
      of 136 patients who had coronary events during follow-up (mean 6.2 years) were
      compared with those in 136 age- and gender-matched patients from the same trial
      without subsequent coronary events. RESULTS: Mean titers of IgG and IgA
      antibodies were similar in cases and controls. The relative odds of future
      coronary events in patients who were seropositive at baseline were 1.0 (95% CI,
      0.54-1.84) for IgG and 0.74 (95% CI, 0.41-1.31) for IgA. The relative odds did
      not change after adjustment for multiple confounding variables. The risk of
      future coronary events did not increase with increasing anti-Chlamydia pneumoniae
      antibody titers. CONCLUSIONS: Prior exposure to Chlamydia pneumoniae in patients
      with chronic coronary heart disease is not associated with increased risk of
      recurrent coronary events.

PMID- 14729432
TI  - T wave alternans is a predictor of death in patients with congestive heart
      failure.
AB  - Few data are available about the prognostic role of T wave alternans in patients
      with congestive heart failure. To assess the ability of T wave alternans, used
      alone or in combination with other risk markers, to predict cardiac death in
      decompensated patients, we enrolled 46 patients, mean age 59+/-9, males 89%,
      ischemic etiology 61%, NYHA class III 35%, left ventricular ejection fraction
      29+/-7%. After 1.6 years follow-up, seven patients died from cardiac death (16%),
      non-sudden in six (86%) and sudden in one (14%). T wave alternans was positive in
      24 (52%), negative in 13 (28%), indeterminate in nine patients (20%). T wave
      alternans was positive in all patients with events (100%) but only in 16 of 37
      patients without (41%) (P=0.02). Other predictors of cardiac death were O(2)
      consumption at the peak of exercise (P=0.03), standard deviation of all NN
      intervals (P=0.05) and Wedge pressure (P=0.03). When receiver operator
      characteristics curves were calculated, the highest area (0.73) was found for
      O(2) consumption at the peak of exercise considering the single variables and for
      O(2) consumption at the peak of exercise plus T wave alternans (0.79) for
      combination of them; the comparison of the two receiver operator characteristics
      curves did not reach statistical difference (P=0.5). In conclusion, this is the
      first study reporting that T wave alternans can predict cardiac death, with a
      marginal additional prognostic power when used in combination with measurement of
      O(2) consumption at the peak of exercise.

PMID- 14729433
TI  - Seasonal distribution of acute myocardial infarction and its relation to acute
      infections in a mild climate.
AB  - BACKGROUND: There is evidence that acute myocardial infraction (aMI) occurs more
      frequently in certain seasons and months of the year. Recently various infectious
      agents have been implicated in atherogenesis. In the present study we recorded
      the seasonal distribution of aMI and evaluated its relation to acute systemic
      infections (AIs). METHODS: The study included 1196 patients with aMI hospitalized
      during the years 1988-1998 in the General Hospital of the island of Rhodes and
      2976 patients with AI during the years 1993-1998. Foreigners or visitors in the
      island were excluded to avoid their influence in the annual distribution. We
      corrected the absolute number of the aMI and AI cases by month and season in such
      a way that all months and seasons would have standard 30 and 90 days,
      respectively. RESULTS: During the entire period of the study, more patients with
      aMI were hospitalized in winter [30.7%, 95% confidence limits (CL) 28.1 to
      33.3%]. In spring the percentage of aMI cases hospitalized was 24.5% (CL 22.1
      27%), in summer 23.2% (CL 20.1-25.6%) and in autumn 21.6% (CL 19.2 -24%). There
      were 42.35% more cases hospitalized in winter than in autumn. The monthly
      distribution showed that March was the month with the most aMI cases (10.83%, CL
      9.06-12.6% ) and October with the fewest (6%, CL 4.65-7.35%). The percentage of
      patients with AI hospitalized in winter was 30.5% (CL 28.8-32.2%), in spring
      25.2% (23.6-26.7), in summer 23.5% (CL 22-25%) and in autumn 20.8% (CL 19.4
      22.3%). The correlation coefficient (r) between the distribution of aMI and AI
      was 0.73 (P<0.01). CONCLUSIONS: Our results indicate that (1) there is a seasonal
      distribution in aMI with the winter being the season of the highest incidence of
      aMI and autumn of the lowest and (2) there is a significant correlation of the
      distribution of aMI to AI cases, which is of interest in the understanding of the
      pathogenesis of acute coronary syndromes.

PMID- 14729434
TI  - Prognostic information provided by serial measurements of brain natriuretic
      peptide in heart failure.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) levels predict prognosis in heart
      failure patients. We aimed to evaluate if serial measurements of BNP can give
      additional prognostic information. METHODS: Eighty-four patients with systolic
      dysfunction had two measurements of BNP with an interval of 8 to 12 months and
      were followed in order to register the occurrence of death. The study was
      observational and prospectively designed. During follow-up, patients were treated
      according to state of the art. Physicians were kept blind to BNP levels. RESULTS:
      The median follow-up was 1190 days. The median initial BNP level was 260.4 pg/ml
      and decreased to 123 pg/ml in the second measurement (P=0.001). The decrease in
      BNP was significantly associated with ACE-i dosage and with the use of a beta
      blocker. All-cause mortality was 20.2%. Patients whose initial BNP level was
      above the median had a significantly higher hazard of dying (HR 2.96, 95% CI 1.06
      8.26). The same was observed for those whose BNP increased between the first and
      the second measurement (HR 2.64, 95% CI 1.00-7.00). In multivariable analysis,
      baseline BNP above the median and increasing BNP were associated with shorter
      survival. CONCLUSIONS: Higher baseline BNP and the increasing levels during
      follow-up were independently associated with mortality. The decrease in BNP
      levels was proportional to ACE-i dosage and larger among patients on beta
      blockers. These results confirm the prognostic information provided by BNP
      determination and suggest that serial measurements give additional prognostic
      information.

PMID- 14729435
TI  - Delayed cardioprotection afforded by nitroglycerin is mediated by alpha-CGRP via
      activation of inducible nitric oxide synthase.
AB  - Previous investigations have demonstrated that delayed preconditioning induced by
      nitroglycerin is mediated by endogenous calcitonin gene-related peptide (CGRP).
      In the present study, we examined whether CGRP-mediated delayed preconditioning
      induced by nitroglycerin is involved in activation of inducible nitric oxide
      synthase (iNOS). Male Wistar rats were pretreated with nitroglycerin 24 h before
      the experiment, and then the left main coronary artery of rat heart was subjected
      to 60-min occlusion followed by 3 h reperfusion. Infarct size, the plasma level
      of cGMP and CGRP, and expression of CGRP isoforms (alpha-CGRP and beta-CGRP) mRNA
      in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (120
      microg/kg, i.v.) markedly reduced infarct size. Nitroglycerin caused a
      significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP
      mRNA, concomitant with an increase in plasma concentrations of cGMP and CGRP.
      These effects of nitroglycerin were completely abolished by pretreatment with
      aminoguanidine (300 mg/kg, i.p.), a selective inhibitor of iNOS activity, or
      dexamethasone (5 mg/kg, i.p.), the iNOS expression inhibitor. The present results
      suggest that delayed cardioprotection afforded by nitroglycerin is mediated by
      the alpha-CGRP isoform via generation of NO derived from iNOS.

PMID- 14729436
TI  - Effects of revascularisation and contractile reserve on left ventricular
      remodelling in patients with impaired left ventricular function.
AB  - OBJECTIVE: We sought to define the influence of revascularisation and contractile
      reserve on left ventricular (LV) remodelling in patients with LV dysfunction
      after myocardial infarction. Revascularisation of viable myocardium is associated
      with improved regional function, but the effect on remodelling is undefined.
      METHODS: We studied 70 patients with coronary artery disease and LV dysfunction,
      31 of whom underwent revascularisation. A standard dobutamine stress
      echocardiogram (DbE) was carried out. All patients underwent standard medical
      treatment; the decision to revascularise was made clinically, independent of this
      study. LV volumes and ejection fraction were measured by 3D echocardiography at
      baseline and after an average of 40 weeks. RESULTS: There was no significant
      difference in baseline ejection fraction or volumes between patients who
      underwent revascularisation and the remainder. Compared to medically treated
      patients, revascularised patients had significant improvements in ejection
      fraction and end-systolic volume in follow-up. The impact of baseline variables
      on remodelling was assessed by dividing patients into tertiles of LV ejection
      fraction and volumes. Revascularised patients in the lowest tertile of ejection
      fraction at baseline (<38%) had a significant improvement in end-systolic volume
      and ejection fraction, larger than obtained in medically treated patients with
      low ejection fraction. Revascularised patients with an ejection fraction >38% did
      not show significant improvement in volumes compared to baseline. Revascularised
      patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume
      (>149 ml) at baseline had a significant improvement in end-systolic volume.
      CONCLUSION: Remodeling appears to occur independent of the presence of regional
      contractile reserve but does correlate with the volume response to low-dose
      dobutamine.

PMID- 14729437
TI  - Big endothelin in chronic heart failure: marker of disease severity or genetic
      determination?
AB  - The first objective of the study was to compare the levels of big endothelin and
      endothelin-1 and other noninvasive parameters used for evaluation of disease
      severity in patients with stable chronic heart failure (CHF). Endothelin-1 and
      big endothelin plasma concentrations were measured in 124 chronic heart failure
      patients. The second objective of the study was to prove an association between
      endothelin-1 and big endothelin plasma levels and two frequent polymorphisms in
      the endothelin-1 coding gene (6p21-23) -3A/-4A and G (8002) A in patients with
      chronic heart failure. Thirdly, we tried to associate other noninvasive
      parameters of CHF, especially cardiothoracic index (CTI), NYHA classification,
      signs of pulmonary congestion (PC) and ejection fraction (EF) with determined
      genotypes of the two ET-1 polymorphic variants. There were significant
      differences between big endothelin levels in NYHA II versus IV (P<0.001) and NYHA
      III versus IV (P<0.001) and endothelin-1 in NYHA II versus IV (P<0.001) and NYHA
      III versus IV (P<0.001). No associations between plasma levels of endothelin-1
      and big endothelin and polymorphisms G (8002) A and -3A/-4A in gene coding
      endothelin-1 were found. In patients with CHF with CTI above 60% the number of
      carriers of genotypes with ET-1 8002A (AA and AG genotypes) increases. Concerning
      on the -3A/-4A ET-1 polymorphism, we observed a significant difference in
      genotype distribution as well as in allelic frequency in the group of patients
      with CTI above 60% between patients without and with pulmonary congestion. The
      allelic frequency of 3A allele is twice elevated in the patients with pulmonary
      congestion (37.8 vs. 78.1%, respectively).

PMID- 14729438
TI  - Correlation between dispersion of repolarization (QT dispersion) and ventricular
      ectopic beat frequency in patients with acute myocardial infarction: a marker for
      risk of arrhythmogenesis?
AB  - BACKGROUND: QT dispersion (QTd) has evoked a lot of interest in recent years as
      regards the basic concept of dispersion of repolarization, which it is supposed
      to reflect on a surface ECG, as being a marker or substrate for arrhythmogenesis.
      QTd has been shown to be high in patients with ventricular fibrillation and
      tachycardia. But there is still some debate about its possible role as a marker
      or substrate for arrhythmogenesis. We studied whether it has any correlation with
      simple benign ventricular ectopic beats (VEB) after acute myocardial infarction.
      STUDY: We studied four different dispersion parameters (QTd, QTcd, JTcd, AQTd) on
      2 different days after AMI and also obtained a 24-h ambulatory ECG on the 2nd day
      after admission in 64 out of a total of 90 patients. Patients were divided into
      five groups based on VEB frequency/h on a 24-h ambulatory ECG. RESULTS: We found
      a gradual increase in dispersion parameters across the five groups with
      increasing frequency of VEB. A significant difference was noticed between group 1
      (VEB 0.0-0.9/h) and group V (>30/h) on the day of admission: QTd 88.8+/-28.5
      versus 123.3+/-23.4, P<0.02; QTcd 100.5+/-27.6 versus 160.3+/-30.7, P<0.01; JTcd
      95.5+/-31.0 versus 160.4+/-30.9, P<0.01; AQTd 29.6+/-8.2 versus 48.6+/-13.7,
      P<0.01. We also noticed a significant positive correlation between VEB frequency
      and dispersion parameters on both days. CONCLUSION: We hypothesize that with
      increasing dispersion of repolarization the chances or the frequency of
      ventricular arrhythmias increase. Our findings also point to a definite role of
      QTd as an arrhythmogenic marker or substrate.

PMID- 14729439
TI  - Too big became too small.

PMID- 14729440
TI  - Percutaneous coronary intervention in a nonagenarian woman for intractable post
      infarction angina.

PMID- 14729441
TI  - Cardiovascular magnetic resonance of asymptomatic myocardial infarction.

PMID- 14729442
TI  - Diffuse alveolar hemorrhage following administration of tirofiban in a patient
      with acute coronary syndrome: a fatal complication.

PMID- 14729443
TI  - Young female with hemochromatosis.

PMID- 14729444
TI  - Nefazodone-associated torsade de pointes.

PMID- 14729445
TI  - Retinal artery macroaneurysm as initial presentation of hypertension.
AB  - A case of uncontrolled hypertension with a vitreoretinal hemorrhage due to a
      retinal artery macroaneurysm of the right eye and chorio-retinal scars of the
      left eye as initial symptom of hypertension is presented. End organ damage was
      undiagnosed until an intraocular hemorrhage appeared in the right eye. The
      hemorrhage and retinal macroaneursym disappeared spontaneously with proper
      medical therapy for hypertension.

PMID- 14729446
TI  - Delayed myocardial perforation following pacemaker implantation.
AB  - Myocardial perforation is a rare complication following pacemaker implantation
      that may cause cardiac tamponade. If it does occur, it is usually at the time of
      lead insertion. This condition requires urgent recognition since the prompt
      drainage of the pericardial fluid may be lifesaving. We present a case report of
      myocardial perforation complicated by cardiac tamponade 4 days after pacemaker
      lead insertion that was repaired surgically.

PMID- 14729447
TI  - On the role of oxidative stress and neutrophils in myocardial reperfusion injury.

PMID- 14729448
TI  - Differential expression of cyclooxygenase-1 and cyclooxygenase-2 in the cornea
      during wound healing.
AB  - Cyclooxygenases (COXs) are the key enzymes in the production of prostaglandins
      (PGs) and exist in two isoforms. Isoform 1 (COX-1) is constitutively expressed in
      most tissues, whereas cyclooxygenase-2 (COX-2) is rapidly induced by a variety of
      different stimuli. In this study, we have quantitatively analyzed mRNA expression
      of COX-1 and COX-2 and protein distribution during corneal reparative processes
      after wound. Total RNA was isolated from cornea samples of New Zealand rabbits
      that had been subjected to corneal wound by mechanical brush scraping.
      Quantification of RT-PCR results was made by using a DNA mimic approach. The
      localization and expression of the enzymes was studied by immunocytochemistry and
      Western blotting. In normal corneas COX-1 is expressed throughout the cornea in
      the whole tissue, while COX-2 is strongly expressed in stromal keratocytes.
      Following injury, COX-2 levels drastically increase and, at least in the
      epithelium, COX-2 becomes the predominant isoform of cyclooxygenases at an early
      stage of healing. Moreover, in the epithelium COX-2 is expressed predominantly by
      those cells close to the wound. These cells become migratory and move toward the
      injured area. In contrast, COX-1 levels remain unaffected in all corneal tissues.
      The system returns to the pre-injury state in about 24h. Thus, the expression of
      COX-2 in the corneal epithelium during wound repair is tightly regulated both
      temporally and spatially.

PMID- 14729449
TI  - Do nuclear bodies in oocytes of Tenebrio molitor (Coleoptera: Polyphaga,
      Tenebrionidae) contain two forms of RNA polymerase II?
AB  - Late vitellogenic oocytes of the mealworm beetle, Tenebrio molitor, which are
      transcriptionally inert, contain numerous fibrogranular nuclear bodies (NBs).
      Previously, we have shown that these NBs contain both unphosphorylated and
      phosphorylated forms of RNA polymerase II (pol II) [Tissue Cell 33 (2001) 549].
      The conclusion on the presence of phosphorylated pol II was based on our
      immunoelectron experiments with monoclonal antibody (mAb) H5 against the
      phosphorylated serine-2 of the carboxy-terminal domain (CTD) of pol II. Because
      the specificity of mAb H5 was recently questioned by demonstration of its cross
      reaction with SR-proteins [J. Struct. Biol. 140 (2002) 154], we re-examined here
      the occurence of pol II in T. molitor oocyte NBs using other appropriate
      antibodies. We confirm the presence of phosphorylated pol II in NBs using the
      affinity-purified polyclonal antibody against the phosphorylated CTD. Using
      double immunogold labeling with this antibody plus mAb 8WG16 against the
      unphosphorylated CTD, we confirm the presence of two forms of pol II in NBs.
      Additionally, the presence of pol II in NBs was verified here using mAb ARNA3
      against the epitope outside CTD. We suggest that at the transcriptionally
      inactive stage, T. molitor oocyte NBs represent storage domains for pol II
      disengaged from the transcription.

PMID- 14729450
TI  - Ultrastructural analysis of progressive endometrial hypercytolipidemia induced by
      obese (ob/ob) and diabetes (db/db) genotype mutations: structural basis of female
      reproductive tract involution.
AB  - The diabetes (db/db) and obese (ob/ob) genotype mutations induce a progressive,
      hypercytolipidemic condition within the endometrium of the female reproductive
      tract that promotes sterility and premature organ involution in C57BL/KsJ mice.
      The current studies focus on the ultrastructural changes that occur within the
      epithelial and stromal layers of the uterine endometrium during the progressive
      expression of these mutations, which induce a hyperglycemic-hyperinsulinemic
      metabolic state and promote tissue cytolipidemia and organoinvolution. Control
      (normal: +/-), diabetes (db/db) and obese (ob/ob) genotype groups were prepared
      for high resolution light (LM) and transmission (TEM) microscopic analysis of
      endometrial tissue samples collected from 4 (young)- to 20 (aged)-week-old mice,
      allowing for the progressive influences of the mutational aberrations on uterine
      structure to be evaluated. Compared to controls, both (ob/ob) and (db/db)
      mutations induced a dramatic increase in endometrial epithelial cytolipid vacuole
      accumulation, which increased in density between 4 and 20 weeks of age. Lipid
      vacuoles aggregated at the baso-polar regions of epithelial cells in response to
      the hyperglycemic-hyperlipidemic conditions typical of both (ob/ob) and (db/db)
      groups. Progressive cytoplasmic movement of the lipid pools induced a perinuclear
      isolation from surrounding cytoplasmic organelles. Apical lipid accumulations
      forced cytoplasmic organelles into peripheral cell compartments and altered the
      periepithelial stromal cell profile relative to controls. These studies define
      the progressive, intracellular accumulation of hypercytolipidemic pools which
      induce a transformation of normal endometrial cell types into adipocyte-like
      entities. The lipidemia-induced alterations in cell structure disrupt normal
      tissue continuity and function, culminating in organoinvolution and overt female
      reproductive sterility.

PMID- 14729451
TI  - Structure and ultrastructure of spermatozoa in Meliponini (stingless bees)
      (Hymenoptera: Apidae).
AB  - In spite of their importance in the reproduction of phanerograms, few bees have
      received an adequate description of their sperm ultrastructure. In this study, we
      concluded that it was possible to define a characteristic pattern for Meliponini
      spermatozoa. However, we have also found species-specific differences that could
      be used, for example, in a taxonomic or phylogenetic evaluation. Meliponini
      spermatozoa are made up of a head and a flagellar region. The head includes an
      acrosome containing the perforatorium, covered by the acrosomal vesicle and a
      nucleus. In transverse sections, the acrosome is circular at the tip but becomes
      triangular as it nears the nucleus. The perforatorium base penetrates into a
      small cavity in the nuclear tip. The flagellum consists of an axoneme, a pair of
      mitochondrial derivatives, a centriolar adjunct and a pair of accessory bodies.
      The axoneme has a typical 9+9+2 microtubule pattern. In the final portion, the
      axoneme becomes gradually disorganized with the accessory microtubules
      terminating last. The mitochondrial derivatives are asymmetric in length and
      diameter. In cross-section, they are ellipsoidal and the larger one has a
      paracrystalline region. The centriolar adjunct begins at the nuclear base and
      extends parallel to the axoneme up to the anterior end of the smaller
      mitochondrial derivative.

PMID- 14729452
TI  - A symbiont of the tick Ixodes ricinus invades and consumes mitochondria in a mode
      similar to that of the parasitic bacterium Bdellovibrio bacteriovorus.
AB  - We have recently performed molecular characterisation of an intracellular alpha
      proteobacterium, named IricES1, which resides in the ovarian tissue of female
      Ixodes ricinus ticks from Italy. A unique characteristic of this bacterium is its
      ability to invade the mitochondria of the cells in which it resides. Although
      some ultrastructural studies have been performed on close relatives of this
      bacterium from I. ricinus in England and Switzerland, a number of questions
      remain about its movement within ovarian tissues and mitochondria. We have
      performed the first detailed ultrastructural examination of IricES1 in engorged
      female adult I. ricinus. Among our findings was that the bacterium enters
      mitochondria in a similar way to that employed by the 'predatory' bacterium
      Bdellovibro bacteriovorus, that is, between the inner and outer membranes. It
      then appears to multiply, with the new 'colony' consuming the mitochondrial
      matrix. Despite having many of their mitochondria consumed, oocytes appear to
      develop normally, and the bacteria are likely to be vertically transferred to all
      eggs.

PMID- 14729453
TI  - Ratios between number of neuroglial cells and number and volume of nerve cells in
      the spinal ganglia of two species of reptiles and three species of mammals.
AB  - We studied the ratios between number of neuroglial (=satellite) cells and number
      and volume of neurons with which they are associated in the spinal ganglia of two
      species of reptiles (lizard and gecko) and three species of mammals (mouse, rat,
      and rabbit). In all five species, we found that the number of satellite cells
      associated with a nerve cell body increased with increasing volume of the latter.
      This result shows that there is a quantitative balance between neuroglia and
      nerve tissue in spinal ganglia. This balance seems to be maintained by a tight
      regulation of the number of satellite cells. We also found that the mean volume
      of nerve cell body corresponding to a satellite cell was lower for small neurons
      than for large ones. Since satellite cells metabolically support spinal ganglion
      neurons, the metabolic needs of small neurons are better satisfied than those of
      large ones. For a nerve cell body of a given size, the number of associated
      satellite cells did not differ between the lizard and gecko, nor between the
      mouse, rat, and rabbit. However, this number was significantly smaller in the
      reptiles than in the mammals. This result could be explained by the lower
      metabolic rate in the nervous system of poikilotherms than mammals, or could have
      a phylogenetic significance. These two interpretations are not mutually
      exclusive.

PMID- 14729454
TI  - Spermatozoal ultrastructures of two marine perciform teleost fishes, the
      goatfish, Paraupeneus spilurus (Mullidae) and the rabbitfish, Siganus fuscescens
      (Siganidae) from Taiwan.
AB  - Mature spermatozoa of two perciform teleost fishes, Paraupeneus spilurus
      (Mullidae) and Siganus fuscescens (Siganidae) from Taiwan were examined using
      transmission and scanning electron microscopy. Despite the fact that spermatozoa
      of both species are of the primitive type, the results of the present study
      highlight the potential application of spermatozoal morphology in studies of fish
      phylogenetic relationships. To our knowledge, the flattened nucleus observed in
      P. spilurus spermatozoa is reported for the first time. Several features common
      to Sigandae spermatozoa-the unusual almost parallel situation of the centrioles,
      the arrangement of mitochondria and the near absence of shallow nuclear fossa-are
      significantly different from other common teleost sperm types. These unique
      features may be synapomorphies for the Siganidae and Mullidae and evidently
      contribute to the study of phylogenetic relationships in teleosts.

PMID- 14729455
TI  - Downregulation of N1 gene expression inhibits the initial heartbeating and heart
      development in axolotls.
AB  - Recessive mutant gene c in the axolotl results in a failure of affected embryos
      to develop contracting hearts. This abnormality can be corrected by treating the
      mutant heart with RNA isolated from normal anterior endoderm or from endoderm
      conditioned medium. A cDNA library was constructed from the total conditioned
      medium RNA using a random priming technique in a pcDNAII vector. We have
      previously identified a clone (designated as N1) from the constructed axolotl
      cDNA library, which has a unique nucleotide sequence. We have also discovered
      that the N1 gene product is related to heart development in the Mexican axolotl
      [Cell Mol. Biol. Res. 41 (1995) 117]. In the present studies, we further
      investigate the role of N1 on heartbeating and heart development in axolotls. N1
      mRNA expression has been determined by using semi-quantitative RT-PCR with
      specifically designed primers. Normal embryonic hearts (at stages 30-31) have
      been transfected with anti-sense oligonucleotides against N1 to determine if
      downregulation of N1 gene expression has any effect on normal heart development.
      Our results show that cardiac N1 mRNA expression is partially blocked in the
      hearts transfected with anti-sense nucleotides and the downregulation of N1 gene
      expression results in a decrease of heartbeating in normal embryos, although the
      hearts remain alive as indicated by calcium spike movement throughout the hearts.
      Confocal microscopy data indicate some myofibril disorganization in the hearts
      transfected with the anti-sense N1 oligonucleotides. Interestingly, we also find
      that N1 gene expression is significantly decreased in the mutant axolotl hearts.
      Our results suggest that N1 is a novel gene in Mexican axolotls and it probably
      plays an important role in myofibrillogenesis and in the initiation of
      heartbeating during heart development.

PMID- 14729456
TI  - Subcellular localization and oligomeric structure of the yeast putative stretch
      activated Ca2+ channel component Mid1.
AB  - The yeast Mid1 protein with an apparent molecular mass of 100 kDa is required for
      Ca2+ influx stimulated by the mating pheromone and by a capacitative calcium
      entrylike mechanism acting in response to Ca2+ depletion from the endoplasmic
      reticulum (ER) and functions as a stretch-activated Ca2+ -permeable channel when
      expressed in mammalian cells. Our previous work with protease protection
      experiments has indicated that Mid1 is present in the plasma membrane. In this
      study, we examined a possible intracellular localization of this protein by
      indirect fluorescence microscopy and found that Mid1 is present in the ER
      membrane as well as the plasma membrane. Intracellular fluorescence images for
      Mid1 were the same as those for the ER marker protein Sec71 but quite different
      from those of the Golgi protein Ypt1. The results were confirmed by membrane
      fractionation using Angiografin density gradient analysis. We also investigated
      the oligomeric structures and protein levels of Mid1 and found that Mid1 forms a
      200-kDa oligomer by disulfide bonding. The protein level and modification of Mid1
      in the plasma membrane and the ER membrane were unchanged by the mating
      pheromone. These findings provide new insight into the function of Mid1 in
      relation to localization, modification, and activation mechanisms.

PMID- 14729457
TI  - Inhibition of p38 mitogen-activated protein kinase reduces TNF-induced activation
      of NF-kappaB, elicits caspase activity, and enhances cytotoxicity.
AB  - Among other cellular responses, tumor necrosis factor (TNF) induces different
      forms of cell death and the activation of the p38 mitogen-activated protein
      kinase (MAPK). The influence of p38 MAPK activation on TNF-induced apoptosis or
      necrosis is controversially discussed. Here, we demonstrate that pharmacological
      inhibition of p38 MAPK enhances TNF-induced cell death in murine fibroblast cell
      lines L929 and NIH3T3. Furthermore, overexpression of dominant-negative versions
      of p38 MAPK or its upstream kinase MKK6 led to increased cell death in L929
      cells. While overexpression of the p38 isoforms alpha and beta did not protect
      L929 cells from TNF-induced toxicity, overexpression of constitutively active
      MKK6 decreased TNF-induced cell death. Although the used inhibitors of p38 MAPK
      decreased the phosphorylation of the survival kinase PKB/Akt, this effect could
      be ruled out as cause of the observed sensitization to TNF-induced cytotoxicity.
      Finally, we demonstrate that the nuclear factor kappaB (NF-kappaB)-dependent gene
      expression, shown as an example for the anti-apoptotic gene cellular inhibitor of
      apoptosis (c-IAP2), was reduced by p38 MAPK inhibition. In consequence, we found
      that inhibition of p38 MAPK led to the activation of the executioner caspase-3.

PMID- 14729458
TI  - Cell adhesion molecule T-cadherin regulates vascular cell adhesion, phenotype and
      motility.
AB  - T-cadherin (T-cad), an unusual glycosylphosphatidylinositol (GPI)-anchored member
      of the cadherin family of cell adhesion molecules, is widely expressed in the
      cardiovascular system. The expression profile of T-cad within diseased
      (atherosclerotic and restenotic) vessels indicates some relationship between
      expression of T-cad and the phenotypic status of resident cells. Using cultures
      of human aortic smooth muscle cells (SMC) and human umbilical vein endothelial
      cells (HUVEC) we investigate the hypothesis that T-cad may function in modulating
      adhesive properties of vascular cells. Coating of culture plates with recombinant
      T-cad protein or with antibody against the first amino-terminal domain of T-cad
      (anti-EC1) significantly decreased adhesion and spreading of SMC and HUVEC.
      HUVECs adherent on T-cad or anti-EC1 substratum exhibited an elongated morphology
      and associated redistribution of the cytoskeleton and focal adhesions to a
      distinctly peripheral location. These changes are characteristic of the less
      adhesive, motile or pro-migratory, pro-angiogenic phenotype. Boyden chamber
      migration assay demonstrated that the deadhesion induced by T-cad facilitates
      cell migration towards a serum gradient. Overexpression of T-cad in vascular
      cells using adenoviral vectors does not influence cell adhesion or motility per
      se, but increases the detachment and migratory responses induced by T-cad
      substratum. The data suggest that T-cad acts as an anti-adhesive signal for
      vascular cells, thus modulating vascular cell phenotype and migration properties.

PMID- 14729459
TI  - Transdifferentiation of preadipose cells into smooth muscle-like cells: role of
      aortic carboxypeptidase-like protein.
AB  - Adipocyte differentiation involves dramatic cell shape alterations that are
      accompanied by changes in the expression of cytoskeletal and extracellular matrix
      (ECM) proteins. Aortic carboxypeptidase-like protein (ACLP) is a secreted protein
      associated with the extracellular matrix whose expression is induced during
      smooth muscle (SM) differentiation. We analyzed the expression of ACLP gene
      during adipocyte differentiation of 3T3-F442A, 3T3-L1, and Ob1771 preadipocytes.
      Our results show that ACLP mRNA and protein are expressed in growing cells and
      after commitment. Thereafter, their expression levels decrease, as opposed to
      that of aP2 and PPARgamma2. Consistent with these observations, ACLP mRNA is
      expressed in the stromal-vascular fraction of adipose tissue but not in the
      adipocyte fraction. Overexpression of ACLP in 3T3-F442A preadipocytes inhibits
      adipocyte differentiation at both morphological and molecular level. However,
      ACLP overexpression promotes transdifferentiation of preadipocytes into smooth
      muscle-like cells, which express specific markers such as SM22alpha, SM alpha
      actin, SM-MHC, and caldesmon. These findings demonstrate that overexpression of a
      single extracellular matrix protein is sufficient to induce transdifferentiation
      and that ACLP may modulate the commitment of mesodermal cells into different
      lineages depending upon its pattern of expression.

PMID- 14729460
TI  - Significant variations in differentiation properties between independent mouse ES
      cell lines cultured under defined conditions.
AB  - Mouse embryonic stem (ES) cells are isolated from the inner cell mass
      (ICM)/epiblast of preimplantation embryos and are widely used in cell
      differentiation studies. We have previously observed differences in transcript
      and antigen expression following differentiation of ES cells lines in vitro. We
      have investigated this further by comparing the differentiation characteristics
      of five independently derived ES cell lines cultured and differentiated under
      defined conditions. Undifferentiated ES cell lines exhibited similar morphology
      and antigen/transcript marker expression. However, upon differentiation in
      monolayer culture by LIF withdrawal, only two of the lines expressed similar germ
      layer transcript profiles, and these were significantly altered compared to
      differentiation in serum-supplemented media. Neurofilament-68k was the only
      transcript marker common to all cell lines, however, induction of neuroectoderm
      lineages using 1 microM all-trans retinoic acid (RA) resulted in significant
      variations in cell number and morphology between the lines. Furthermore, neurons
      were only formed from clones of the two cell lines that exhibited similar
      transcript profiles, although the morphology was different between the two. We
      conclude that the independent ES cell lines in this study differ in their
      response to alterations in culture conditions in vitro, and the use of an
      appropriate cell line enables relatively homogeneous neuronal populations to be
      achieved in monolayer culture under defined conditions.

PMID- 14729461
TI  - Growth factors and nonparenchymal cell conditioned media induce mitogenic
      responses in stable long-term adult rat hepatocyte cultures.
AB  - Most prior studies have characterized hepatocyte proliferative responses in
      culture systems that do not express a stable differentiated phenotype. We
      investigated the DNA synthetic response of long-term stable hepatocyte cultures
      to growth factor stimulation as well as conditioning with nonparenchymal cells
      (NPCs). Primary rat hepatocytes were cultured on a single layer of collagen (h/C)
      or Matrigel (h/M), or in a collagen sandwich (C/h/C) or collagen-Matrigel
      sandwich (M/h/C). Hepatocytes were cultured for 7 days to allow phenotypic
      stabilization before growth factor addition, except for h/C cultures, which are
      unstable, where growth factors were added 1 day after seeding. Culture medium was
      supplemented with a mixture of hepatocyte, epidermal, and vascular endothelial
      growth factors and interleukin-6, either directly or after conditioning with NPCs
      for 24 h. Growth factors alone induced hepatocyte DNA synthesis, as measured via
      [3H]thymidine uptake, in the h/C, C/h/C, and M/h/C configurations. h/M exhibited
      very low levels of DNA synthesis. In the C/h/C and M/h/C configurations, the
      greatest stimulation was obtained using NPC-conditioned growth factors. This
      response was sustained for several days and without decreasing albumin or urea
      synthesis. These results suggest that hepatocyte mitogens and NPC-derived factors
      can stimulate DNA synthesis in stable and differentiated hepatocyte cultures.

PMID- 14729462
TI  - Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell
      that surrounds the nucleolus.
AB  - Nuclear DNA helicase II (NDH II), alternatively named RNA helicase A (RHA), is an
      F-actin binding protein that is particularly enriched in the nucleolus of mouse
      cells. Here, we show that the nucleolar localization of NDH II of murine 3T3
      cells depended on an ongoing rRNA synthesis. NDH II migrated out of the nucleolus
      after administration of 0.05 microg/ml actinomycin D, while nucleolin and the
      upstream binding factor (UBF) remained there. In S phase-arrested mouse cells,
      NDH II was frequently found at the nucleolar periphery, where it was accompanied
      by newly synthesized nucleolar RNA. Human NDH II was mainly distributed through
      the whole nucleoplasm and not enriched in the nucleoli. However, in the human
      breast carcinoma cell line MCF-7, NDH II was also found at the nucleolar
      periphery, together with the tumor suppressor protein p53. Both NDH II and p53
      were apparently attached to the F-actin-based filamentous network that surrounded
      the nucleoli. Accordingly, this subnuclear structure was sensitive to F-actin
      depolymerizing agents. Depolymerization with gelsolin led to a striking
      accumulation of NDH II in the nucleoli of MCF-7 cells. This effect was abolished
      by RNase, which extensively released nucleolus-bound NDH II when added together
      with gelsolin. Taken together, these results support the idea that an actin-based
      filamentous network may anchor NDH II at the nucleolar periphery for pre
      ribosomal RNA processing, ribosome assembly, and/or transport.

PMID- 14729463
TI  - Direct cell-cell interaction enhances pro-MMP-2 production and activation in co
      culture of laryngeal cancer cells and fibroblasts: involvement of EMMPRIN and MT1
      MMP.
AB  - Matrix metalloproteinases-2 (MMP-2, gelatinase A) has been regarded as a crucial
      enzyme for tumor progression, invasion, and metastasis by its capability to
      degrade the basement membrane components, and its activation process is critical
      for tumor development. Recently, EMMPRIN/CD147, which is a member of
      immunoglobulin superfamily, has been reported to be highly expressed in tumor
      cells and induce production of MMPs from fibroblasts adjacent to the tumor cells.
      In this study, we demonstrated that production of pro- and active forms of MMP-2
      by human dermal fibroblasts was enhanced by the direct cell-cell contact with co
      cultured HEp-2 cells derived from a human laryngeal epidermoid carcinoma. The
      results from immunoblotting and reverse transcription-polymerase chain reaction
      (RT-PCR) analysis indicated that HEp-2 cells express a higher level of EMMPRIN
      but only a low level of MMP-2 and membrane type 1-matrix metalloproteinase (MT1
      MMP), whereas fibroblasts express a higher level of MMP-2 and MT1-MMP and a low
      level of EMMPRIN. In a mixed co-culture with direct cell-cell contacts, co
      cultured HEp-2 cells stimulated the pro- and active MMP-2 production from
      fibroblasts, but not in a separated co-culture through polycarbonate membrane.
      Production of pro/active MMP-2 and MT1-MMP (activator of pro-MMP-2) in
      fibroblasts was induced by the addition of membrane fractions prepared from HEp-2
      cells to the fibroblast culture, and the induction was suppressed by the EMMPRIN
      depletion after immunoprecipitation, signifying the participation of EMMPRIN for
      the induction and activation of MMP-2. Our results suggest an importance of the
      direct cell-cell interaction involving EMMPRIN rather than humoral factors such
      as cytokines for pro-MMP-2 production and activation followed by tumor
      progression, invasion, and metastasis in laryngeal cancer.

PMID- 14729464
TI  - Growth factors regulate beta-catenin-mediated TCF-dependent transcriptional
      activation in fibroblasts during the proliferative phase of wound healing.
AB  - Beta-catenin is a critical regulator of cell behavior during embryogenesis and
      neoplastic processes. It also plays a crucial role in repair by modulating dermal
      fibroblast activity during the proliferative phase of cutaneous wound healing. We
      hypothesize that growth factors liberated during the initial phase of wound
      healing convey signals to induce activation of beta-catenin-mediated TCF
      dependent signaling during the proliferative phase. Dermal fibroblasts were
      isolated and cultured from mice containing a beta-galactosidase reporter
      responsive to beta-catenin-TCF transactivation (TCF-beta-gal). Cells were
      stimulated with growth factors present at the initial phase of wound healing. EGF
      and TGF-beta1 significantly increased beta-catenin protein levels and
      transcriptional activity, whereas beta-catenin mRNA expression was unaffected.
      This increase was attributed to inactivation of GSK-3beta, a kinase important for
      beta-catenin destabilization. Subcutaneous injection of EGF or TGF-beta1 before
      wounding of TCF-beta-gal mice resulted in larger scars and fibroblasts within
      these wounds that strongly stained for beta-galactosidase, indicating significant
      beta-catenin transcriptional activity in vivo. Thus, beta-catenin-mediated
      signaling is activated downstream of growth factors released during the initial
      phase of wound repair, and may act during the proliferative phase of wound
      healing to integrate signals from initial phase factors into the expression of
      genes important during the later, remodeling phase.

PMID- 14729465
TI  - MgcRacGAP regulates cortical activity through RhoA during cytokinesis.
AB  - Although Rho GTPases regulate multiple cellular events, their role in cell
      division is still obscure. Here we show that expression of a GTPase-activating
      protein (GAP)-deficient mutant (R386A) of the Rho regulator MgcRacGAP induces
      abnormal cortical activity during cytokinesis in U2OS cells. Multiple large blebs
      were observed in cells expressing MgcRacGAP R386A from the onset of anaphase to
      the late stage of cell division. When mitotic blebbing was excessive, cytokinesis
      was inhibited, and cells with micronuclei were generated. It has been reported
      that blebbing is caused by abnormal cortical activity. The MgcRacGAP R386A
      induced abnormal cortical activity was inhibited by the dominant negative form of
      RhoA, but not Rac1 or Cdc42. Moreover, expression of constitutively active RhoA
      also induced drastic cortical activity during cytokinesis. Unlike apoptotic
      blebbing, MgcRacGAP R386A-induced blebbing was not inhibited by the ROCK
      inhibitor Y-27632, suggesting that MgcRacGAP regulates cortical activity during
      cytokinesis through a novel signaling pathway. We propose that MgcRacGAP plays a
      pivotal role in cytokinesis by regulating cortical movement through RhoA.

PMID- 14729466
TI  - Changes in biophysical parameters of plasma membranes influence cisplatin
      resistance of sensitive and resistant epidermal carcinoma cells.
AB  - The mechanism of resistance of cancer cells to the anticancer drug cisplatin is
      not fully understood. Using cisplatin-sensitive KB-3-1 and -resistant KCP-20
      cells, we found that the resistant cells have higher membrane potential, as
      determined by membrane potential sensing oxonol dye. Electron spin resonance and
      fluorescence polarization studies revealed that the resistant cells have more
      "fluid" plasma membranes than the sensitive cells. Because of this observed
      difference in membrane "fluidity," we attempted modification of the plasma
      membrane fluidity by the incorporation of heptadecanoic acid into KB-3-1 and KCP
      20 cell membranes. We found that such treatment resulted in increased
      heptadecanoic acid content and increased fluidity in the plasma membranes of both
      cell types, and also resulted in increased cisplatin resistance in the KCP-20
      cells. This finding is in accord with our results, which showed that the
      cisplatin-resistant KCP-20 cells have more fluid membranes than the cisplatin
      sensitive KB-3-1 cells. It remains to be determined whether the observed
      differences in biophysical status and/or fatty acid composition alone, or the
      secondary effect of these differences on the structure or function of some
      transmembrane protein(s), is the reason for increased cisplatin resistance.

PMID- 14729467
TI  - Relevance of an in vitro osteoclastogenesis system to study receptor activator of
      NF-kB ligand and osteoprotegerin biological activities.
AB  - Receptor activator of NF-kB Ligand (RANKL) is an essential requirement for
      osteoclastogenesis and its activity is neutralized by binding to the soluble
      decoy receptor osteoprotegerin (OPG). The purpose of this work was to study the
      effects of RANKL and OPG during osteoclastogenesis using the murine monocytic
      cell line RAW 264.7 that can differentiate into osteoclasts in vitro. RAW 264.7
      cells plated at 10(4) cells/cm(2) and cultured for 4 days in the presence of
      RANKL represent the optimal culture conditions for osteoclast differentiation,
      with an up-regulation of all parameters related to bone resorption: tartrate
      resistant acid phosphatase (TRAP), calcitonin receptor (CTR), RANK, cathepsin K,
      matrix metalloproteinase (MMP)-9 mRNA expressions. RANKL and OPG biological
      effects vary according to the differentiation state of the cells: in
      undifferentiated RAW 264.7 cells, TRAP expression was decreased by OPG and RANKL,
      RANK expression was inhibited by OPG, while MMP-9 and cathepsin K mRNA
      expressions were not modulated. In differentiated RAW 264.7 cells, RANKL and OPG
      both exert an overall inhibitory effect on the expression of all the parameters
      studied. In these experimental conditions, OPG-induced MMP-9 inhibition was
      abrogated in the presence of a blocking anti-RANKL antibody, suggesting that part
      of OPG effects are RANKL-dependent.

PMID- 14729469
TI  - Homeodomain-interacting protein kinase-2 activity and p53 phosphorylation are
      critical events for cisplatin-mediated apoptosis.
AB  - HIPK2 is a member of a novel family of nuclear serine-threonine kinases
      identified through their ability to interact with the Nkx-1.2 homeoprotein. The
      physiological role of these kinases is largely unknown, but we have recently
      reported on the involvement of HIPK2 in the induction of apoptosis of tumor cells
      after UV stress through p53 phosphorylation and transcriptional activation. Here,
      we demonstrate that the chemotherapeutic drug cisplatin increases HIPK2 protein
      expression and its kinase activity, and that HIPK2 is involved in cisplatin
      dependent apoptosis. Indeed, induction of HIPK2 and of cell death by cisplatin
      are efficiently inhibited by the serine-threonine kinase inhibitor SB203580 or
      the transduction of HIPK2-specific RNA-interfering molecules. HIPK2 gene
      silencing efficiently reduces the p53-mediated transcriptional activation of
      apoptotic gene promoters as well as apoptotic cell death after treatment with
      cisplatin. These findings, along with the involvement of p53 phosphorylation at
      serine 46 (Ser46) in the transcriptional activation of apoptotic gene promoters,
      suggest a critical role for HIPK2 in triggering p53-dependent apoptosis in
      response to the antineoplastic drug cisplatin.

PMID- 14729468
TI  - Role of caspases-3 and -7 in Apaf-1 proteolytic cleavage and degradation events
      during cisplatin-induced apoptosis in melanoma cells.
AB  - Apoptosis protease-activating factor-1 (Apaf-1), the central element in the
      mitochondrial pathway of apoptosis, is frequently absent or poorly expressed in
      metastatic melanomas, a tumor type showing a low degree of spontaneous apoptosis
      and a poor response to conventional therapies. In the present study, we used the
      Apaf-1-positive Me665/2/21 melanoma cell line to investigate the fate of Apaf-1
      during cisplatin-induced apoptosis. As novel findings described for the first
      time in melanoma cells, we observed that Apaf-1 was markedly decreased during
      apoptosis, already at early stages of cell damage; concurrently, an
      immunoreactive N-terminal fragment of congruent with 26 kDa was evident. In spite
      of the remarkable decrease of Apaf-1 in apoptotic cells, caspase-9 was found to
      be processed and enzymatically active. Both Apaf-1 depletion and its proteolytic
      cleavage were markedly prevented in presence of the caspase-3/-7 inhibitor ac
      DEVD-CHO. In presence of ac-DEVD-CHO, caspase-9 activity was also inhibited,
      along with a partially different pattern of caspase-9 processing forms.
      Unexpectedly, the inhibition afforded by ac-DEVD-CHO on several components, that
      is, caspase-3/-7 and caspase-9 activities, and Apaf-1 proteolytic degradation,
      did not abrogate the apoptotic morphology and cell detachment, nor the
      proteolytic degradation of crucial targets, such as poly(ADP-ribose) polymerase
      (PARP) and lamin B. Together, our results suggest that caspase-3 and -7, proved
      to be dispensable for the above apoptosis-associated events, play a role on Apaf
      1 handling and possibly on apoptosome function.

PMID- 14729470
TI  - Hemopoietic cell transformation is associated with failure to downregulate
      glucose uptake during the G2/M phase of the cell cycle.
AB  - Growth factors and cytokines initiate multiple signal transduction pathways that
      lead to cell survival, cell cycle progression or differentiation. A common
      feature of these pathways is increased cellular metabolism and glucose uptake.
      Furthermore, the energy requirements of many cancers and transformed cell lines
      are met by constitutive upregulation of glucose uptake. Relationships among
      transforming events, glucose uptake and cell cycle progression are not well
      understood. Here we investigated the regulation of glucose transport during the
      cell cycle of growth factor-dependent 32D cells, primary T-cells, src-transformed
      32D cells and Jurkat cells. Cells were enriched in the G1, S and G2/M phases of
      the cell cycle, and glucose transporter expression and 2-deoxyglucose uptake were
      measured. Glucose transporter expression increased with cell volume as cells
      progressed through the cell cycle. Growth factor-dependent 32D cells and T
      lymphocytes were characterised by increased 2-deoxyglucose uptake from G1 to S
      and reduced uptake at G2/M, with the highest specific activity of transporters in
      the S phase. In contrast, src-transformed 32D cells and Jurkat cells showed
      increased 2-deoxyglucose uptake from S to G2/M, with the highest glucose
      transporter specific activity in G2/M. Our results show that glucose transport is
      regulated in a cell cycle-dependent manner and suggest that this regulation may
      be altered in transformed cells.

PMID- 14729471
TI  - The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation
      of primary, but not HPV16 E6/E7-immortalized human endothelial cells.
AB  - Immunohistochemical analysis has demonstrated that the human IFI16 gene, in
      addition to the hematopoietic tissues, is highly expressed in endothelial cells
      and squamous stratified epithelia. In this study, we have developed a reliable
      HSV-derived replication-defective vector (TO-IFI16) to efficiently transduce
      IFI16 into primary human umbilical vein endothelial cells (HUVEC), which are
      usually poorly transfectable. HUVEC infection with TO-IFI16 virus suppressed
      endothelial migration, invasion and formation of capillary-like structures in
      vitro. In parallel, sustained IFI16 expression inhibited HUVEC cell cycle
      progression, accompanied by significant induction of p53, p21, and
      hypophosphorylated pRb. Further support for the involvement of these pathways in
      IFI16 activity came from the finding that infection with TO-IFI16 virus does not
      impair the in vitro angiogenic activity and cell cycle progression of HUVEC
      immortalized by HPV16 E6/E7 oncogenes, which are known to inactivate both p53 and
      pRb systems. This use of a reliable viral system for gene delivery into primary
      human endothelial cells assigns a potent angiostatic activity to an IFN-inducible
      gene, namely IFI16, and thus throws further light on antiangiogenic therapy
      employing IFNs.

PMID- 14729472
TI  - Correlation between nucleocytoplasmic transport and caspase-3-dependent
      dismantling of nuclear pores during apoptosis.
AB  - During apoptosis (also called programmed cell death), the chromatin condenses and
      the DNA is cleaved into oligonucleosomal fragments. Caspases are believed to play
      a major role in nuclear apoptosis. However, the relation between dismantling of
      nuclear pores, disruption of the nucleocytoplasmic barrier, and nuclear entry of
      caspases is unclear. We have analyzed nuclear import of the green fluorescent
      protein fused to a nuclear localization signal (GFP-NLS) in tissue culture cells
      undergoing apoptosis. Decreased nuclear accumulation of GFP-NLS could be detected
      at the onset of nuclear apoptosis manifested as dramatic condensation and
      redistribution of chromatin toward the nuclear periphery. At this step,
      dismantling of nuclear pores was already evident as indicated by proteolysis of
      the nuclear pore membrane protein POM121. Thus, disruption of nuclear
      compartmentalization correlated with early signs of nuclear pore damage. Both
      these events clearly preceded massive DNA fragmentation, detected by TUNEL assay.
      Furthermore, we show that in apoptotic cells, POM121 is specifically cleaved at
      aspartate-531 in its large C-terminal portion by a caspase-3-dependent mechanism.
      Cleavage of the C-terminal portion of POM121, which is adjoining the nuclear pore
      complex, is likely to disrupt interactions with other nuclear pore proteins
      affecting the stability of the pore complex. A temporal correlation of apoptotic
      events supports a model where caspase-dependent disassembly of nuclear pores and
      disruption of the nucleocytoplasmic barrier paves the way for nuclear entry of
      caspases and subsequent activation of CAD-mediated DNA fragmentation.

PMID- 14729473
TI  - Distinct pools of proliferating cell nuclear antigen associated to DNA
      replication sites interact with the p125 subunit of DNA polymerase delta or DNA
      ligase I.
AB  - Proliferating cell nuclear antigen (PCNA) plays an essential role in DNA
      replication, repair, and cell cycle control. PCNA is a homotrimeric ring that,
      when encircling DNA, is not easily extractable. Consequently, the dynamics of
      protein-protein interactions established by PCNA at DNA replication sites is not
      well understood. We have used DNase I to release DNA-bound PCNA together with
      replication proteins including the p125-catalytic subunit of DNA polymerase delta
      (p125-pol delta), DNA ligase I, cyclin A, and cyclin-dependent kinase 2 (CDK2).
      Interaction with these proteins was investigated by immunoprecipitation with
      antibodies binding near the interdomain connector loop or to the C-terminal
      domain of PCNA, respectively, or with antibodies to p125-pol delta or DNA ligase
      I. PCNA interaction with p125-pol delta or DNA ligase I was detected only by the
      latter antibodies, and found to be mutually exclusive. In contrast, antibodies to
      PCNA co-immunoprecipitated only CDK2. A GST-p21(waf1/cip1) C-terminal peptide
      displaced p125-pol delta and DNA ligase I, but not CDK2, from PCNA. These results
      suggest that PCNA trimers bound to DNA during the S phase are organized as
      distinct pools able to bind selectively different partners. Among them, p125-pol
      delta and DNA ligase I interact with PCNA in a mutually exclusive manner.

PMID- 14729474
TI  - Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle
      development.
AB  - Calcineurin signaling has been implicated in a broad spectrum of developmental
      processes in a variety of organ systems. Calcineurin is a calmodulin-dependent,
      calcium-activated protein phosphatase composed of catalytic and regulatory
      subunits. The serine/threonine-specific phosphatase functions within a signal
      transduction pathway that regulates gene expression and biological responses in
      many developmentally important cell types. Calcineurin signaling was first
      defined in T lymphocytes as a regulator of nuclear factor of activated T cells
      (NFAT) transcription factor nuclear translocation and activation. Recent studies
      have demonstrated the vital nature of calcium/calcineurin/NFAT signaling in
      cardiovascular and skeletal muscle development in vertebrates. Inhibition,
      mutation, or forced expression of calcineurin pathway genes result in defects or
      alterations in cardiomyocyte maturation, heart valve formation, vascular
      development, skeletal muscle differentiation and fiber-type switching, and
      cardiac and skeletal muscle hypertrophy. Conserved calcineurin genes are found in
      invertebrates such as Drosophila and Caenorhabditis elegans, and genetic studies
      have demonstrated specific myogenic functions for the phosphatase in their
      development. The ability to investigate calcineurin signaling pathways in
      vertebrates and model genetic organisms provides a great potential to more fully
      comprehend the functions of calcineurin and its interacting genes in heart, blood
      vessel, and muscle development.

PMID- 14729475
TI  - Molecular and functional analysis of apical junction formation in the gut
      epithelium of Caenorhabditis elegans.
AB  - The Caenorhabditis elegans intestine is a simple and accessible model system to
      analyze the mechanism of junction assembly. In comparison to Drosophila and
      vertebrates, the C. elegans apical junction is remarkable because a single
      electron-dense structure is implicated in complex processes such as epithelial
      tightness, vectorial transport and cell adhesion. Here we present evidence in
      support of a heterogeneous molecular assembly of junctional proteins found in
      Drosophila and vertebrate epithelia associated with different junctions or
      regions of the plasma membrane. In addition, we show that molecularly diverse
      complexes participate in different aspects of epithelial maturation in the C.
      elegans intestine. DLG-1 (Discs large) acts synergistically with the catenin
      cadherin complex (HMP-1-HMP-2-HMR-1) and the Ezrin-Radixin-Moesin homolog (ERM-1)
      to ensure tissue integrity of the intestinal tube. The correct localization of
      DLG-1 itself depends on AJM-1, a coiled-coil protein. Double depletion of HMP-1
      (alpha-catenin) and LET-413 (C. elegans homolog of Drosophila Scribble) suggests
      that the catenin-cadherin complex is epistatic to LET-413, while additional
      depletion of subapically expressed CRB-1 (Crumbs) emphasizes a role of CRB-1
      concerning apical junction formation in the C. elegans intestine.

PMID- 14729476
TI  - Ectoderm removal prevents cutaneous nerve formation and perturbs sensory axon
      growth in the chick hindlimb.
AB  - Target tissues are thought to provide important cues for growing axons, yet there
      is little direct evidence that they are essential for axonal pathfinding. Here we
      examined whether target ectoderm is necessary for the formation of cutaneous
      nerves, and for the normal growth and guidance of cutaneous axons as they first
      enter the limb plexus. To do this, we removed a patch of ectoderm from the chick
      hindlimb at various times during early axon outgrowth. We find there is a
      critical period when cutaneous nerve formation requires target ectoderm. When the
      ectoderm is absent during this time, axons progress into the limb more slowly
      and, although a few sensory axons occasionally diverge a short distance from the
      plexus, they do not form a discrete nerve that travels to the skin. A few days
      later, when the nerve pattern is mature, axons normally destined for the
      'deprived' cutaneous nerve are not segregated appropriately within the plexus.
      Some cutaneous axons are instead misdirected along an inappropriate cutaneous
      nerve, while others have seemingly failed to reach their correct target, or a
      suitable alternative, and died. These results demonstrate that the target
      ectoderm is necessary for normal sensory axon growth and guidance in the
      hindlimb.

PMID- 14729477
TI  - Formation, architecture and polarity of female germline cyst in Xenopus.
AB  - Little is known about the formation of germline cyst and the differentiation of
      oocyte within the cyst in vertebrates. In the majority of invertebrates in the
      initial stages of gametogenesis, male and female germ cells develop in full
      synchrony as a syncytia of interconnected cells called germline cysts (clusters,
      nests). Using electron microscopy, immunostaining and three-dimensional
      reconstruction, we were able to elucidate the process of cyst formation in the
      developing ovary of the vertebrate Xenopus laevis. We found that the germline
      cyst in Xenopus contains 16 cells that are similar in general architecture and
      molecular composition to the cyst in Drosophila. Nest cells are connected by
      cytoplasmic bridges that contain ring canal-like structures. The nest cells
      contain a structure similar to the Drosophila fusome that that is probably
      involved in anchoring of the centrioles and organization of the primary
      mitochondrial cloud (PMC) around the centriole. We also find that in contrast to
      other organisms, in Xenopus, apoptosis is a rare event within the developing
      ovary. Our studies indicate that the processes responsible for the formation of
      female germline cysts and the establishment of germ cell polarity are highly
      conserved between invertebrates and vertebrates. The dissimilarities between
      Drosophila and Xenopus and the uniqueness of each system probably evolved through
      modifications of the same fundamental design of the germline cyst.

PMID- 14729478
TI  - Rapid H1 linker histone transitions following fertilization or somatic cell
      nuclear transfer: evidence for a uniform developmental program in mice.
AB  - H1 linker histones (H1s) are key regulators of chromatin structure and function.
      The functions of different H1s during early embryogenesis, and mechanisms
      regulating their associations with chromatin are largely unknown. The
      developmental transitions of H1s during oocyte growth and maturation,
      fertilization and early embryogenesis, and in cloned embryos were examined.
      Oocyte-specific H1FOO, but not somatic H1s, associated with chromatin in oocytes
      (growing, GV-stage, and MII-arrested), pronuclei, and polar bodies. H1FOO
      associated with sperm or somatic cell chromatin within 5 min of intracytoplasmic
      sperm injection (ICSI) or somatic cell nuclear transfer (SCNT), and completely
      replaced somatic H1s by 60 min. The switching from somatic H1s to H1FOO following
      SCNT was developmentally regulated. H1FOO was replaced by somatic H1s during the
      late two- and four-cell stages. H1FOO association with chromatin can occur in the
      presence of a nuclear envelope and independently of pronucleus formation, is
      regulated by factors associated with the spindle, and is likely an active
      process. All SCNT constructs recapitulated the normal sequence of H1 transitions,
      indicating that this alone does not signify a high developmental potential. A
      paucity of all known H1s in two-cell embryos may contribute to precocious gene
      transcription in fertilized embryos, and the elaboration of somatic cell
      characteristics in cloned embryos.

PMID- 14729479
TI  - Rapid replacement of somatic linker histones with the oocyte-specific linker
      histone H1foo in nuclear transfer.
AB  - The most distinctive feature of oocyte-specific linker histones is the specific
      timing of their expression during embryonic development. In Xenopus nuclear
      transfer, somatic linker histones in the donor nucleus are replaced with oocyte
      specific linker histone B4, leading to the involvement of oocyte-specific linker
      histones in nuclear reprogramming. We recently have discovered a mouse oocyte
      specific linker histone, named H1foo, and demonstrated its expression pattern in
      normal preimplantation embryos. The present study was undertaken to determine
      whether the replacement of somatic linker histones with H1foo occurs during the
      process of mouse nuclear transfer. H1foo was detected in the donor nucleus soon
      after transplantation. Thereafter, H1foo was restricted to the chromatin in up to
      two-cell stage embryos. After fusion of an oocyte with a cell expressing GFP
      (green fluorescent protein)-tagged somatic linker histone H1c, immediate release
      of H1c in the donor nucleus was observed. In addition, we used fluorescence
      recovery after photobleaching (FRAP), and found that H1foo is more mobile than
      H1c in living cells. The greater mobility of H1foo may contribute to its rapid
      replacement and decreased stability of the embryonic chromatin structure. These
      results suggest that rapid replacement of H1c with H1foo may play an important
      role in nuclear remodeling.

PMID- 14729480
TI  - Expression of type II iodothyronine deiodinase marks the time that a tissue
      responds to thyroid hormone-induced metamorphosis in Xenopus laevis.
AB  - The thyroid gland synthesizes thyroxine (T4), which passes through the larval
      tadpole's circulatory system. The enzyme type II iodothyronine deiodinase (D2)
      converts thyroxine (T4) to the active hormone 3,5,3'-triiodothyronine (T3) in
      peripheral tissues. An early response to thyroid hormone (TH) in the Xenopus
      laevis tadpole is the stimulation of cell division in cells that line the brain
      ventricles, the lumen of the spinal cord, and the limb buds. These cells express
      constitutively high levels of D2 mRNA. Exogenous T4 induces early DNA synthesis
      in brain, spinal cord, and limb buds as efficiently as T3. The deiodinase
      inhibitor iopanoic acid blocks T4- but not T3-induced cell division. At
      metamorphic climax, both TH-induced cell division and D2 expression decrease in
      the brain. Then D2 expression appears in late-responding tissues including the
      anterior pituitary, the intestine, and the tail where cell division is reduced or
      absent. Therefore, constitutive expression of D2 occurs in the earliest target
      tissues of TH that will grow and differentiate, while TH-induced expression of D2
      takes place in late-responding tissues that will remodel or die. This pattern of
      constitutive and induced D2 expression contributes to the timing of metamorphic
      changes in these tissues.

PMID- 14729481
TI  - Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway.
AB  - Cleft palate is among the most common birth defects in humans, caused by a
      failure in the complex multistep developmental process of palatogenesis. It has
      been recently shown that transforming growth factor beta3 (Tgf-beta3) is an
      absolute requirement for successful palatal fusion, both in mice and humans.
      However, very little is known about the mechanisms of Tgf-beta3 signaling during
      this process. Here we show that putative Tgf-beta type I receptors, Alk-1, Alk-2,
      and Alk-5, are all endogenously expressed in the palatal epithelium. Activation
      of Alk-5 in the Tgf-beta3 (-/-) palatal epithelium is able to rescue palatal
      fusion, whereas inactivation of Alk-5 in the wild-type palatal epithelium
      prevents palatal fusion. The effect of Alk-2 is similar, but less pronounced. The
      induction of fusion by activation of Alk-5 or Alk-2 is stronger in the posterior
      parts of the palates at the embryonic day 14 (E14), while their activation at
      E13.5 also restores anterior fusion, reflecting the natural anterior-posterior
      direction of palate maturation in vivo. We also show that Smad2 is endogenously
      activated in the palatal midline epithelial seam (MES) during the fusion process.
      By using a mutant Alk-5 receptor that is an active kinase but is unable to
      activate Smads, we show that activation of Smad-independent Tgf-beta responses is
      not sufficient to induce fusion of shelves deficient in Tgf-beta3. Based on these
      observations, we conclude that the Smad2-dependent Alk-5 signaling pathway is
      dominant in palatal fusion driven by Tgf-beta3.

PMID- 14729483
TI  - The initiation of Hox gene expression in Xenopus laevis is controlled by
      Brachyury and BMP-4.
AB  - Hox genes encode a family of transcription factors that specify positional
      identities along the anterior-posterior (AP) axis during the development of
      vertebrate embryos. The earliest Hox expression in vertebrates is during
      gastrulation, at a position distant from the organiser or its equivalent.
      However, the mechanism that initiates this early expression is still not clear.
      Guided by the expression pattern, we identified upstream regulators in Xenopus
      laevis. The mesodermal transcription factor brachyury (Xbra) controls the early
      Hox expression domain in the animal-vegetal direction and the secreted growth
      factor BMP-4 limits it in the organiser/non-organiser direction. The overlap of
      these two signals, indicated by a Cartesian coordinate system, defines the
      initial Hox expression domain. We postulate that this system is a general
      mechanism for the activation of all Hox genes expressed during gastrulation.

PMID- 14729482
TI  - Morphogenesis of chicken liver: identification of localized growth zones and the
      role of beta-catenin/Wnt in size regulation.
AB  - During development and regeneration, new cells are added and incorporated to the
      liver parenchyma. Regulation of this process contributes to the final size and
      shape of the particular organs, including the liver. We identified the
      distribution of liver growth zones using an embryonic chicken model because of
      its accessibility to experimentation. Hepatocyte precursors were first generated
      all over the primordia surrounding the vitelline blood vessel at embryonic day 2
      (E2), then became limited to the peripheral growth zones around E6.
      Differentiating daughter cells of the peripheral hepatocyte precursors were shown
      by DiI microinjection to be laid inward and were subsequently organized to form
      the hepatic architecture. At E8, hepatocyte precursor cells were further
      restricted to limited segments of the periphery, called localized growth zones
      (LoGZ). Adhesion and signaling molecules in the growth zone were studied. Among
      them, beta-catenin and Wnt 3a were highly enriched. We overexpressed
      constitutively active beta-catenin using replication competent avian sarcoma
      (RCAS) virus. Liver size increased about 3-fold with an expanded hepatocyte
      precursor cell population. In addition, blocking beta-catenin activity by either
      overexpression of dominant-negative LEF1 or overexpression of a secreted Wnt
      inhibitor Dickkopf (DKK) resulted in decreased liver size with altered liver
      shape. Our data suggest that (1) the duration of active growth zone activity
      modulates the size of the liver; (2) a shift in the position of the localized
      growth zone helps to shape the liver; and (3) beta-catenin/Wnt are involved in
      regulating growth zone activities during liver development.

PMID- 14729484
TI  - Fgf and Bmp signals repress the expression of Bapx1 in the mandibular mesenchyme
      and control the position of the developing jaw joint.
AB  - The development of the jaw joint between the palatoquadrate and proximal part
      Meckel's cartilage (articular) has recently been shown to involve the gene Bapx1.
      Bapx1 is expressed in the developing mandibular arch in two distinct caudal,
      proximal patches, one on either side of the head. These domains coincide later
      with the position of the developing jaw joint. The mechanisms that result in the
      restricted expression of Bapx1 in the mandibular arch were investigated, and two
      signaling factors that act as repressors were identified. Fibroblast growth
      factors (Fgfs) expressed in the oral epithelium restrict expression of Bapx1 to
      the caudal half of the mandibular arch, while bone morphogenetic proteins (Bmps)
      expressed in the distal mandibular arch restrict expression of Bapx1 to the
      proximal part of the mandible. Application of Fgf8 and Bmp4 beads to the proximal
      mesenchyme led to loss of Bapx1 expression and later fusion of the quadrate and
      articular as the jaw joint failed to form. In addition to fusion of the jaw
      joint, loss of Bapx1 lead to loss of the retroarticular process (RAP),
      phenocopying the defects seen after Bapx1 function was reduced in the zebrafish.
      By manipulating these signals, we were able to alter the expression domain of
      Bapx1, resulting in a new position of the jaw joint.

PMID- 14729485
TI  - The Caenorhabditis elegans homolog of the putative prostate cancer susceptibility
      gene ELAC2, hoe-1, plays a role in germline proliferation.
AB  - The potential prostate cancer susceptibility gene ELAC2 has a Caenorhabditis
      elegans homolog (which we call hoe-1, for homolog of ELAC2). We have explored the
      biological role of this gene using RNAi to reduce gene activity. We found that
      worms subjected to hoe-1 RNAi are slow-growing and sterile. The sterility results
      from a drastic reduction in germline proliferation and cell-cycle arrest of
      germline nuclei. We found that hoe-1 is required for hyperproliferation
      phenotypes seen with mutations in three different genes, suggesting hoe-1 may be
      generally required for germline proliferation. We also found that reduction of
      hoe-1 by RNAi suppresses the multivulva (Muv) phenotype resulting from activating
      mutations in ras and that this suppression is likely to be indirect. This is the
      first demonstration of a biological role for this class of proteins in a complex
      eukaryote and adds important information when considering the role of ELAC2 in
      prostate cancer.

PMID- 14729486
TI  - Murine numb regulates granule cell maturation in the cerebellum.
AB  - Notch is a key regulator of vertebrate neurogenesis and the cytoplasmic adaptor
      protein Numb is a modulator of the Notch signaling pathway. To address the role
      of murine Numb in development of the central nervous system, we used a
      conditional gene ablation approach. We show that Numb is involved in the
      maturation of cerebellar granule cells. Although the specification of neural cell
      fates in the cerebellum is not affected in the absence of Numb, the transition
      from a mitotic progenitor to a mature granule cell is aberrant and migration of
      postmitotic granule cells to the internal granule cell layer is delayed. In some
      animals, this results in a complete agenesis of granule cells and a strong
      ataxia. We confirmed these findings in vitro and found that Numb-deficient
      cerebellar progenitor cells show a marked delay in granule cell maturation. Our
      results suggest that Numb plays a role in the transition of a mitotic progenitor
      to a fully differentiated granule cell in the cerebellum. In addition, the
      maturation of Purkinje cells is also delayed in Numb-deficient mice.

PMID- 14729487
TI  - The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic
      beta-cell differentiation.
AB  - Pancreatic beta cells play a central role in maintaining glucose homeostasis
      because they secrete insulin in response to increased level of blood glucose;
      failure of this capacity constitutes a major component of the pathogenesis of
      diabetes. The identification of key regulators of pancreatic beta-cell
      differentiation is relevant for the overall understanding of this process and for
      future experiments aimed at regenerating insulin-producing beta cells from
      pancreatic or embryonic stem cells. Several studies using transgenic or knockout
      mice have established that the development and function of pancreatic beta cells
      are controlled by several genes encoding specific transcription factors. By
      inactivating the homeobox gene Pax4, we previously demonstrated that its function
      is required for the formation of mature insulin-producing cells. Here, we show
      that during pancreas ontogeny, Pax4 is expressed in differentiating endocrine
      cells, including beta cells. Pax4 activity appears essential for appropriate
      initiation of beta-cell differentiation because loss of Pax4 prevents the
      expression of Pdx1, HB9 and insulin in beta-cell precursors. This role of Pax4
      appears to be accomplished via its genetic interaction with another homeobox
      gene, Nkx2.2.

PMID- 14729488
TI  - Regulation of the paternal inheritance of centrosomes in starfish zygotes.
AB  - In most animals, fertilized eggs inherit one centrosome from a meiosis-II spindle
      of oocytes and another centrosome from the sperm. However, since first proposed
      by Boveri [Sitzungsber. Ges. Morph. Phys. Munch. 3 (1887) 151-164] at the turn of
      the last century, it has been believed that only the paternal (sperm) centrosome
      provides the division poles for mitosis in animal zygotes. This uniparental
      (paternal) inheritance of centrosomes is logically based on the premise that the
      maternal (egg) centrosome is lost before the onset of the first mitosis. For the
      processes of the selective loss of the maternal centrosome, three models have
      been proposed: One stresses the intrinsic factors within the centrosome itself;
      the other two emphasize external factors such as cytoplasmic conditions or the
      sperm centrosome. In the present study, we have examined the validity of one of
      the models in which the sperm centrosome overwhelms the maternal centrosomes.
      Because centrosomes cast off into both the first and the second polar bodies (PB)
      are known to retain the capacity for reproduction and cell-division pole
      formation, we observed the behavior of those PB centrosomes with reproductive
      capacity and the sperm centrosome in the same zygotic cytoplasm. We prepared two
      kinds of fertilized eggs that contain reproductive maternal centrosomes, (1) by
      micromanipulative transplantation of the PB centrosomes into fertilized eggs, and
      (2) by suppression of the PB extrusions of fertilized eggs with cytochalasin B.
      In both types of eggs, the PB centrosomes could double and form cell-division
      poles, indicating that they are not suppressed by the sperm centrosome, which in
      turn indicates that selective loss of the maternal centrosome is due to intrinsic
      factors within the centrosomes themselves.

PMID- 14729489
TI  - Oocyte regulation of anti-Mullerian hormone expression in granulosa cells during
      ovarian follicle development in mice.
AB  - In the ovarian follicle, anti-Mullerian hormone (Amh) mRNA is expressed in
      granulosa cells from primary to preovulatory stages but becomes restricted to
      cumulus cells following antrum formation. Anti-Mullerian hormone regulates
      follicle development by attenuating the effects of follicle stimulating hormone
      on follicle growth and inhibiting primordial follicle recruitment. To examine the
      role of the oocyte in regulating granulosa cell Amh expression in the mouse,
      isolated oocytes and granulosa cells were co-cultured and Amh mRNA levels were
      analysed by real-time RT-PCR. Expression in freshly isolated granulosa cells
      increased with preantral follicle development but was low in the cumulus and
      virtually absent in the mural granulosa cells of preovulatory follicles. When
      preantral granulosa cells were co-cultured with oocytes from early preantral,
      late preantral or preovulatory follicles, and when oocytes from preovulatory
      follicles were co-cultured with cumulus granulosa cells, Amh expression was
      increased at least 2-fold compared with granulosa cells cultured alone. With
      oocytes from preantral but not preovulatory follicles, this was a short-range
      effect only observed with granulosa cells in close apposition to oocytes. We
      conclude that stage-specific oocyte regulation of Amh expression may play a role
      in intra- and inter-follicular coordination of follicle development.

PMID- 14729490
TI  - Inhibition of protein tyrosine kinase activity disrupts early retinal
      development.
AB  - In the present study, we have investigated the role of tyrosine kinase activity
      during early retinal development in Xenopus laevis. The protein tyrosine kinase
      (PTK) inhibitors lavendustin A and genistein were used to determine the possible
      role of tyrosine kinase activity during retinal development in vivo and in vitro.
      Application of the inhibitors to early embryonic retina disrupted the pattern of
      lamination in the developing retina. The plexiform layers were severely
      disorganized or were no longer apparent, and photoreceptor morphogenesis was
      disrupted. Immunocytochemical analysis verified the presence of focal adhesions
      in dissociated retinal neuroepithelial cells isolated from St 25 embryos.
      Application of the PTK inhibitors blocked focal adhesion assembly in these
      primary cultured cells. To further investigate the regulation of focal adhesions
      by PTK activity, we examined the effect of lavendustin A on cultured XR1 glial
      cells. Lavendustin A produced a dose-dependent decrease in the proportion of XR1
      cells displaying focal adhesions. Taken together, these results suggest that
      tyrosine kinase activity is essential for regulating neuroepithelial cell
      adhesion, migration and morphogenesis during retinal development. Furthermore,
      the disruption of retinal development may, in part, be due to the inhibition of
      integrin-mediated signaling.

PMID- 14729505
TI  - Recent advances in imaging the lungs of intact small animals.
AB  - A new generation of imaging devices now make it possible to generate both
      structural and functional images for the study of lung biology in small animals,
      including common laboratory mouse and rat models. "Micro" X-ray computed
      tomography and positron emission tomography scanners, highly sensitive cooled
      charge coupled device cameras for bioluminescence and fluorescence imaging, high
      magnetic field magnetic resonance imaging scanners, and recent advances in
      ultrasound system technology can be used to study such diverse processes as
      ventilation, perfusion, pulmonary hypertension, lung inflammation, and gene
      transfer, among others. Images from more than one modality can also be fused,
      allowing structure-function and function-function relationships to be studied on
      a regional basis. These new instruments, part of an emerging suite of techniques
      collectively known as "molecular imaging," provide an enormous potential for
      elucidating lung biology in intact animal models and systems.

PMID- 14729506
TI  - Salmeterol, a beta2-receptor agonist, attenuates lipopolysaccharide-induced lung
      inflammation in mice.
AB  - Lipopolysaccharide is ubiquitously present in the environment. To determine the
      effect of salmeterol, a long-acting beta(2)-receptor agonist, on
      lipopolysaccharide-induced lung inflammation, mice received lipopolysaccharide
      (10 microg) intranasally with or without salmeterol intraperitoneally (5 mg/kg)
      30 min earlier and 12 h thereafter. Salmeterol dose- and time-dependently
      inhibited the lipopolysaccharide-induced influx of neutrophils into
      bronchoalveolar lavage fluid and lung tissue, and these pulmonary neutrophils
      displayed a reduced expression of CD11b at their surface. To determine the
      contribution of the salmeterol effect on neutrophil CD11b in the attenuated
      neutrophil recruitment, we treated mice intranasally exposed to
      lipopolysaccharide with salmeterol with or without a blocking anti-CD11b
      antibody. Anti-CD11b profoundly reduced lipopolysaccharide-induced neutrophil
      influx in bronchoalveolar lavage fluid, an effect that was modestly enhanced by
      concurrent salmeterol treatment. These data suggest that salmeterol inhibits
      lipopolysaccharide-induced neutrophil recruitment to the lungs by a mechanism
      that possibly in part is mediated by an effect on neutrophil CD11b.

PMID- 14729507
TI  - Molecular identity and function in transepithelial transport of K(ATP) channels
      in alveolar epithelial cells.
AB  - K(+) channels play a crucial role in epithelia by repolarizing cells and
      maintaining electrochemical gradient for Na(+) absorption and Cl(-) secretion. In
      the airway epithelium, the most frequently studied K(+) channels are KvLQT1 and
      K(Ca). A functional role for K(ATP) channels has been also suggested in the lung,
      where K(ATP) channel openers activate alveolar clearance and attenuate ischemia
      reperfusion injury. However, the molecular identity of this channel is unknown in
      airway and alveolar epithelial cells (AEC). We adopted an RT-PCR strategy to
      identify, in AEC, cDNA transcripts for Kir channels (Kir6.1 or 6.2) and
      sulfonylurea receptors (SUR1, 2A, or 2B) forming K(ATP) channels. Only Kir6.1 and
      SUR2B were detected in freshly isolated and cultured alveolar cells. To determine
      the physiological role of K(+) channels in the transepithelial transport of
      alveolar monolayers, we studied the effect, on total short-circuit currents
      (I(sc)), of basolateral application of glibenclamide, an inhibitor of K(ATP)
      channels, as well as clofilium, charybdotoxin, clotrimazole, and iberiotoxin,
      inhibitors of KvLQT1 and K(Ca) channels, respectively. Interestingly, activity of
      the three types of K(+) channels was detected, since all tested inhibitors
      decreased I(sc). Furthermore, these K(+) channel inhibitors reduced amiloride
      sensitive Na(+) currents (mediated by ENaC) and completely abolished stimulation
      of Cl(-) currents by forskolin. Conversely, pinacidil, an activator of K(ATP)
      channels, increased Na(+) and Cl(-) transepithelial transport by 33-35%. These
      results suggest the presence, in AEC, of a K(ATP) channel, formed from Kir6.1 and
      SUR2B subunits, which plays a physiological role, with KvLQT1 and K(Ca) channels,
      in Na(+) and Cl(-) transepithelial transport.

PMID- 14729508
TI  - Proinflammatory activity of anti-IL-8 autoantibody:IL-8 complexes in alveolar
      edema fluid from patients with acute lung injury.
AB  - A significant fraction of IL-8 in lung fluids from patients with the acute lung
      injury (ALI) is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8
      complexes), and lung fluid concentrations of these complexes correlate with
      development and outcome of ALI. In this study, we examined whether anti-IL-8:IL-8
      complexes exhibit proinflammatory activity in vitro. These complexes were
      purified from pulmonary edema fluid samples obtained from patients with ALI.
      First, we found that IL-8 bound to the autoantibody retained its ability to
      trigger chemotaxis of neutrophils, whereas control antibody did not have
      significant chemotactic activity. Next, we examined the ability of anti-IL-8:IL-8
      complexes to induce neutrophil activation, i.e., neutrophil respiratory burst and
      degranulation. Anti-IL-8:IL-8 complexes triggered superoxide and myeloperoxidase
      release from human neutrophils, and in contrast, the control antibody had no
      effect. We also demonstrated that IgG receptor, FcgammaRIIa, is the receptor
      involved in cellular activation mediated by these complexes. Blockade of
      FcgammaRIIa completely reverses activity of the complexes with the exception of
      chemotaxis. Both FcgammaRIIa and IL-8 receptors mediate chemotactic activity of
      anti-IL-8:IL-8 complexes, with FcgammaRIIa being, however, a predominant
      receptor. Furthermore, activity of the complexes is partially dependent on the
      activation of the mitogen-activated protein kinases, i.e., ERK and p38, important
      components of the FcgammaRIIa signaling cascade. Anti-IL-8:IL-8 complexes may
      therefore be involved in the pathogenesis of lung inflammation in clinical acute
      lung injury.

PMID- 14729509
TI  - Activation of the STAT pathway in acute lung injury.
AB  - Acute lung injury (ALI) is a devastating clinical problem with a mortality as
      high as 60%. It is now appreciated that ALI represents a cytokine excess state
      that involves the microvasculature of multiple organs. The signal transducers and
      activators of transcription (STAT) family of transcription factors activate
      critical mediators of cytokine responses, but there is limited knowledge about
      their role in mediating ALI. In the present study, we demonstrate that the STAT
      transcription factors are activated rapidly in the lungs after intraperitoneal
      and intranasal LPS administration in mice. We also demonstrated that LPS
      activates both the STAT kinases, Src and JAK, in the lung with kinetics that are
      consistent with STAT activation. LPS treatment resulted in STAT3 activation
      throughout the resident lung cells, as well as in the recruited inflammatory
      cells. Whereas direct LPS treatment did not lead to STAT activation in cultured
      epithelial or endothelial cells, IL-6 activated STAT3 in both of these cell
      types. Furthermore, IL-6 was induced by LPS in serum and in the lung with
      kinetics consistent with STAT3 activation, suggesting that IL-6 may be one
      mechanism of STAT activation by LPS. In addition, STAT activation required
      reactive oxygen species, as the overexpression of catalase in mice prevented LPS
      mediated STAT activation in the lung. STATs may be a common pathway for mediating
      ALI, regardless of the inciting factor, as STAT activation also occurred in both
      a gastric acid aspiration and acute pancreatitis model of ALI. Finally, STATs are
      activated in the lung long before signs of ALI are present, suggesting that the
      STAT transcription factors may play a role in initiating the inflammatory
      response seen in the lung.

PMID- 14729510
TI  - Alveolar macrophages from systemic sclerosis patients: evidence for IL-4-mediated
      phenotype changes.
AB  - The mechanism of chronic lung inflammation leading to lung fibrosis is unknown
      and does not have a characteristic inflammatory macrophage phenotype. This study
      was undertaken to determine whether a change in macrophage phenotype could
      account for chronic lung inflammation. In this study, human alveolar macrophages
      (AM) from subjects with systemic sclerosis (SSc) were obtained from
      bronchoalveolar lavage (BAL) and characterized on the basis of function (response
      to LPS), phenotype, and relative cell-surface B7 expression. AM from the
      subjects' disease-involved and noninvolved lung lobes were compared with each
      other and to AM from normal volunteer BAL. AM from involved SSc lobes produced
      significantly more interleukin (IL)-1beta and PGE(2) than AM from uninvolved
      lobes in response to LPS, but there was no spontaneous production of either
      mediator. The activator AM phenotype designated by RFD1+ surface epitope was
      significantly elevated in SSc BAL samples compared with normal BAL, although
      there were no differences comparing involved vs. noninvolved lobes within SSc
      subjects. The major histocompatibility complex II costimulatory molecule B7.2 was
      also significantly elevated in SSc AM compared with normal AM, again with no
      differences between involved and noninvolved lobes. In an attempt to determine
      environmental influences on AM phenotypes, normal AM were cultured in vitro with
      IFN-gamma, IL-3, IL-4, IL-10, IL-12, or dexamethasone for 6 days. Of the
      cytokines examined, only IL-4 induced significant increases in both the activator
      phenotype RFD1+ and B7.2 expression. Taken together, these results indicate that
      IL-4 could account for proinflammatory AM phenotype changes and B7 surface-marker
      shifts, as seen in subjects with SSc.

PMID- 14729511
TI  - Albumin endocytosis in endothelial cells induces TGF-beta receptor II signaling.
AB  - Vascular endothelial cells undergo albumin endocytosis using a set of albumin
      binding proteins. This process is important for maintaining cellular homeostasis.
      We showed by several criteria that the previously described 73-kDa endothelial
      cell surface albumin binding protein is the 75-kDa transforming growth factor
      (TGF)-beta receptor type II (TbetaRII). Albumin coimmunoprecipitated with
      TbetaRII from a membrane fraction from rat lung microvascular endothelial cells.
      Albumin endocytosis-negative COS-7 cells became albumin endocytosis competent
      when transfected with wild-type TbetaRII but not when transfected with a domain
      negative kinase mutant of TbetaRII. An antibody specific for TbetaRII inhibited
      albumin endocytosis. A mink lung epithelial cell line, which expresses both the
      TGF-beta receptor type I (TbetaRI) and the TbetaRII receptor, exhibited albumin
      binding to the cell surface and endocytosis. In contrast, mutant L-17 and DR-26
      cells lacking TbetaRI or TbetaRII, respectively, each showed a dramatic reduction
      in binding and endocytosis. Albumin endocytosis induced Smad2 phosphorylation and
      Smad4 translocation as well as increased protein expression of the inhibitory
      Smad, Smad7. We identified regions of significant homology between amino acid
      sequences of albumin and TGF-beta, suggesting a structural basis for the
      interaction of albumin with the TGF-beta receptors and subsequent activation of
      TbetaRII signaling. The observed albumin-induced internalization of TbetaRII
      signaling may be an important mechanism in the vessel wall for controlling TGF
      beta responses in endothelial cells.

PMID- 14729512
TI  - In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type
      II epithelial cells.
AB  - It is well established that hyperoxia injures and kills alveolar endothelial and
      type I epithelial cells of the lung. Although type II epithelial cells remain
      morphologically intact, it remains unclear whether they are also damaged. DNA
      integrity was investigated in adult mice whose type II cells were identified by
      their endogenous expression of pro-surfactant protein C or transgenic expression
      of enhanced green fluorescent protein. In mice exposed to room air, punctate
      perinuclear 8-oxoguanine staining was detected in approximately 4% of all
      alveolar cells and in 30% of type II cells. After 48 or 72 h of hyperoxia, 8
      oxoguanine was detected in 11% of all alveolar cells and in >60% of type II
      cells. 8-Oxoguanine colocalized by confocal microscopy with the mitochondrial
      transmembrane protein cytochrome oxidase subunit 1. Type II cells isolated from
      hyperoxic lungs exhibited nuclear DNA strand breaks by comet assay even though
      they were viable and morphologically indistinguishable from cells isolated from
      lungs exposed to room air. These data reveal that type II cells exposed to in
      vivo hyperoxia have oxidized and fragmented DNA. Because type II cells are
      essential for lung remodeling, our findings raise the possibility that they are
      proficient in DNA repair.

PMID- 14729513
TI  - Autoinhibitory domain fragment of endothelial NOS enhances pulmonary artery
      vasorelaxation by the NO-cGMP pathway.
AB  - Catalytic activity of eNOS is regulated by multiple posttranscriptional
      mechanisms, including a 40-amino acid (604-643) autoinhibitory domain (AID)
      located in the reductase domain of the eNOS protein. We examined whether an
      exogenous synthetic AID, an 11-amino acid (626-636) fragment of AID (AAF), or
      scrambled AAF (AAF-SR), enhanced eNOS activity and NO-cGMP-mediated
      vasorelaxation using pulmonary artery (PA) endothelial/smooth muscle cell
      (PAEC/PASM) coculture, isolated PA segment, and isolated lung perfusion models.
      Incubation of isolated total membrane fraction of PAEC with AID or AAF resulted
      in concentration-dependent loss of eNOS activity. In contrast, incubation of
      intact PAEC with AID or AAF but not AAF-SR caused concentration- and time
      dependent activation of eNOS. Because AID and AAF had similar effects on
      activation of eNOS, AAF and AAF-SR were used for further evaluation. Although AAF
      stimulation increased catalytic activity of PKC-alpha in PAEC, AAF-mediated
      activation of eNOS was independent of phosphorylation of Ser1177 or Thr495 and/or
      expression of eNOS protein. AAF stimulation of PAEC increased NO and cGMP
      production, which were attenuated by pretreatment with the eNOS inhibitor l-NAME.
      AAF caused time-dependent vasodilation of U-46619-precontracted endothelium
      intact but not endothelium-denuded PA segments, and this response was attenuated
      by l-NAME. AAF, but not AAF-SR, also caused vasorelaxation in an ex vivo isolated
      mouse lung perfusion model precontracted with U-46619. Incubation with
      fluorescence-labeled AAF demonstrated translocation of AAF in PAEC in culture,
      isolated PA, and isolated intact lungs. These results demonstrate that AAF
      stimulated vasodilation is mediated via activation of eNOS and enhanced NO-cGMP
      production in PA and intact lung.

PMID- 14729514
TI  - Interfacial phospholipids inhibit ozone-reactive absorption-mediated cytotoxicity
      in vitro.
AB  - The intrapulmonary distribution of inhaled ozone (O(3)) and induction of site
      specific cell injury are related to complex interactions among airflow patterns,
      local gas-phase concentrations, and the rates of O(3) flux into, and reaction and
      diffusion within, the epithelial lining fluid (ELF). Recent studies demonstrated
      that interfacial phospholipid films appreciably inhibited NO(2) absorption.
      Because surface-active phospholipids are present on alveolar and airway
      interfaces, we investigated the effects of interfacial films on O(3)-reactive
      absorption and acute cell injury. Compressed films of dipalmitoyl-glycero-3
      phosphocholine (DPPC) and rat lung lavage lipids significantly reduced O(3)
      reactive absorption by ascorbic acid, reduced glutathione, and uric acid.
      Conversely, unsaturated phosphatidylcholine films did not inhibit O(3)
      absorption. We evaluated O(3)-mediated cell injury using a human lung fibroblast
      cell culture system, an intermittent tilting exposure regimen to produce a thin
      covering layer, and nuclear fluorochrome permeability. Exposure produced
      negligible injury in cells covered with MEM. However, addition of AH(2) produced
      appreciable (<50%) cell injury. Film spreading of DPPC monolayers necessitated
      the use of untilted regimens. Induction of acute cell injury in untilted cultures
      required both AH(2) plus very high O(3) concentrations. Addition of DPPC films
      significantly reduced cell injury. We conclude that acute cell injury likely
      results from O(3) reaction with ELF substrates. Furthermore, interfacial films of
      surface-active, saturated phospholipids reduce the local dose of O(3)-derived
      reaction products. Finally, because O(3) local dose and tissue damage likely
      correlate, we propose that interfacial phospholipids may modulate intrapulmonary
      distribution of inhaled O(3) and the extent of site-specific cell injury.

PMID- 14729515
TI  - Hypoxia-induced inhibition of whole cell membrane currents and ion transport of
      A549 cells.
AB  - In excitable cells, hypoxia inhibits K channels, causes membrane depolarization,
      and initiates complex adaptive mechanisms. It is unclear whether K channels of
      alveolar epithelial cells reveal a similar response to hypoxia. A549 cells were
      exposed to hypoxia during whole cell patch-clamp measurements. Hypoxia reversibly
      inhibited a voltage-dependent outward current, consistent with a K current,
      because tetraethylamonium (TEA; 10 mM) abolished this effect; however,
      iberiotoxin (0.1 microM) does not. In normoxia, TEA and iberiotoxin inhibited
      whole cell current (-35%), whereas the K-channel inhibitors glibenclamide (1
      microM), barium (1 mM), chromanol B293 (10 microM), and 4-aminopyridine (1 mM)
      were ineffective. (86)Rb uptake was measured to see whether K-channel modulation
      also affected transport activity. TEA, iberiotoxin, and 4-h hypoxia (1.5% O(2))
      inhibited total (86)Rb uptake by 40, 20, and 35%, respectively. Increased
      extracellular K also inhibited (86)Rb uptake in a dose-dependent way. The K
      channel opener 1-ethyl-2-benzimidazolinone (1 mM) increased (86)Rb uptake by 120%
      in normoxic and hypoxic cells by activation of Na-K pumps (+60%) and Na-K-2Cl
      cotransport (+170%). However, hypoxic transport inhibition was also seen in the
      presence of 1-ethyl-2-benzimidazolinone, TEA, and iberiotoxin. These results
      indicate that hypoxia, membrane depolarization, and K-channel inhibition decrease
      whole cell membrane currents and transport activity. It appears, therefore, that
      a hypoxia-induced change in membrane conductance and membrane potential might be
      a link between hypoxia and alveolar ion transport inhibition.

PMID- 14729516
TI  - Reductions in the incidence of nitrofen-induced diaphragmatic hernia by vitamin A
      and retinoic acid.
AB  - Congenital diaphragmatic hernia (CDH) is a serious medical condition in which the
      developing diaphragm forms incompletely, leaving a hole through which the
      abdominal contents can enter the thoracic space and interfere with lung growth. A
      perturbation of the retinoid system has been linked to the etiology of CDH. This
      includes findings that nitrofen, which induces CDH in rodents, inhibits the key
      enzyme for retinoic acid (RA) production, retinaldehyde dehydrogenase-2 (RALDH2)
      in vitro. Published studies indicate that antenatal vitamin A administration on
      gestational day (D) 12 in the nitrofen model of CDH reduced the severity and
      incidence of right-sided defects and lung hypoplasia. In this study, we
      administered nitrofen on D8, to include the induction of clinically more
      prevalent left-sided defects, and examined the efficacy of several vitamin A
      administration paradigms to gain insights into the developmental stage of
      susceptibility. Furthermore, we tested the hypothesis that administration of RA,
      the product of RALDH2 activity, is more potent than administering the substrate,
      vitamin A, in reducing the incidence of CDH. The incidence of CDH was reduced
      from approximately 54% (nitrofen alone) to approximately 32% with vitamin A
      treatment. The efficacy of RA treatment was very marked, with a reduction in the
      incidence of CDH to approximately 15%. Administration of vitamin A or RA on
      approximately D10 was most effective. These data lend further support for the
      potential involvement of retinoid signaling pathways and the etiology of CDH and
      support data from in vitro studies demonstrating a nitrofen-induced suppression
      of RALDH2.

PMID- 14729517
TI  - Detection of perineural spread: fat suppression versus no fat suppression.

PMID- 14729518
TI  - Is CT perfusion ready for prime time?

PMID- 14729519
TI  - Perineural spread of malignant melanoma of the head and neck: clinical and
      imaging features.
AB  - BACKGROUND AND PURPOSE: Extension of malignant melanoma along cranial nerves is a
      little-known complication of malignant melanoma of the head and neck. We describe
      the clinical and MR imaging findings of perineural spread of malignant melanoma
      to cranial nerves, emphasizing that this entity occurs more commonly with
      desmoplastic histology and may have a long latent period following primary
      diagnosis. METHODS: At two institutions, we identified and retrospectively
      reviewed eight cases of malignant melanoma of the head and neck that had MR
      imaging evidence of perineural spread of disease. All patients underwent
      confirmatory tissue sampling. RESULTS: Seven patients had melanomas of the facial
      skin or lip, and one patient had a primary sinonasal lesion. By histopathology,
      these melanomas included five desmoplastic, two mucosal, and one poorly
      differentiated melanotic spindle-cell tumor. All patients developed symptomatic
      cranial neuropathy an average of 4.9 years from the time of initial diagnosis. MR
      imaging demonstrated postgadolinium enhancement of at least one branch of the
      trigeminal nerve in all cases and of at least one other cranial nerve in five
      cases. Other findings included abnormal contrast enhancement and soft tissue
      thickening in the cavernous sinus, Meckel's cave, and/or the cisternal segment of
      the trigeminal nerve. CONCLUSION: Although perineural spread of disease occurs
      most commonly with squamous cell carcinoma and adenoid cystic carcinoma,
      malignant melanoma must also be included in this differential diagnosis,
      particularly if the patient's pathology is known to be desmoplastic. Similarly,
      any patient with malignant melanoma of the head and neck who undergoes MR imaging
      should receive an imaging assessment focused on the likely routes of perineural
      spread.

PMID- 14729520
TI  - Non-Hodgkin lymphoma of the larynx: CT and MR imaging findings.
AB  - BACKGROUND AND PURPOSE: Non-Hodgkin lymphoma (NHL) of the larynx is a rare tumor.
      The aim of this study was to report the CT and MR features of laryngeal NHL in
      four patients to determine if there are any features that might be helpful to
      distinguish NHL from other laryngeal tumors. METHODS: The CT and MR images of
      four patients with laryngeal NHL were retrospectively reviewed for tumor volume
      and distribution, appearance, local invasion, and lymphadenopathy. RESULTS: Tumor
      volume ranged from 4 to 45 mL(3). Tumor was based in the submucosal (2/4 [50%]),
      mucosal (1/4 [25%]), or both regions (1/4 [25%]) and was centered in the
      supraglottis (4/4 [100%]) but also involved the glottis (4/4 [100%]) and
      subglottis (2/4 [50%]). Laryngeal tumor involved the aryepiglottic folds (4/4
      [100%)]), ventricles and false cords (4/4 [100%]), epiglottis (3/4 [75%]),
      paraglottis (3/4 [75%]), true cords (4/4 [100%]), anterior commissure (4/4
      [100%]), and laryngeal cartilage (1/4 [25%]). The tumor extended into the
      hypopharynx (4/4 [100%]), strap muscles (1/4 [25%]), prevertebral muscles (1/4
      [25%]), tongue base (1/4 [25%]), and walls of the oropharynx (1/4 [25%]) and
      nasopharynx (1/4 [25%]). Bilateral cervical lymphadenopathy with extracapsular
      tumor spread was present in one patient. CONCLUSION: Laryngeal NHL is a tumor
      that usually has a large submucosal component centered in the surpaglottis. The
      tumor extends into the glottis, with less frequent spread to the subglottis,
      laryngeal cartilage, and strap muscles. Laryngeal NHL also involves the
      hypopharynx, with large tumors extending superiorly into the tongue base,
      oropharynx, and nasopharynx. A laryngeal tumor with a large supraglottic
      submucosal component should alert the ragiologist to the possibility of NHL.

PMID- 14729521
TI  - Apparent diffusion coefficient mapping of the normal parotid gland and parotid
      involvement in patients with systemic connective tissue disorders.
AB  - PURPOSE: We hypothesized that a difference in restricted diffusion would exist in
      patients with connective tissue disorders (CTD) as compared with those without
      CTD. Our purpose was to determine whether the apparent diffusion coefficient
      (ADC) measurement could be used to identify parotid abnormalities in patients
      with CTD. METHODS: One neuroradiologist, who was unaware of patient histories,
      retrospectively measured the ADC values for the parotid glands in 121 patients
      who underwent clinically indicated brain MR imaging in which the parotid glands
      were sufficiently depicted. Regions of interest were obtained from both the left
      and right parotid glands. After the medical records were reviewed and exclusion
      criteria were used, 90 non-CTD and seven CTD patients (systemic lupus
      erythematosus = 5; discoid lupus erythematosus = 1; Sjogren syndrome = 1)
      remained. The two groups were then compared. Statistical analysis consisted of
      Wilcoxon sign rank and Mann-Whitney tests. RESULTS: The combined mean ADC for
      both parotid glands in 90 healthy patients was 0.50 +/- 0.28 x 10(-3) mm(2)/s
      (95% CI, 0.44 x 10(-3), 0.56 x 10(-3)). The combined mean ADC for both parotid
      glands in the seven CTD patients was 0.96 +/- 0.24 x 10(-3) mm(2)/s (95% CI, 0.79
      x 10(-3), 1.14 x 10(-3)). The mean ADC for the CTD patients' parotid glands was
      significantly higher than that of the non-CTD patients (P =.0001), which suggests
      there is less restricted diffusion in parotid glands affected by CTD when
      compared with normal parotid glands. CONCLUSION: These results suggest that ADCs
      may be used to detect parotid abnormalities in patients with CTD that are not
      identified by standard imaging. Although preliminary, the results indicate a
      potential role for ADC mapping in detection of subclinical parotid disease.

PMID- 14729522
TI  - The cochlear cleft.
AB  - BACKGROUND AND PURPOSE: Recent advances in the display of medical images permit
      the routine study of temporal bone CT images at high magnification. We noted an
      unfamiliar structure, which we now call the "cochlear cleft," in the otic
      capsule. To our knowledge, this report represents the first description of this
      structure in the medical imaging literature. METHODS: Temporal bone CT performed
      in 100 pediatric patients without sensorineural hearing loss were examined for
      the presence of cochlear clefts. Incidence of cochlear clefts as well as the
      relationship between age and incidence was examined. RESULTS: Cochlear clefts
      were present in 41% of the subjects. Incidence decreased with age. CONCLUSION: We
      describe a cleft in the otic capsule that is frequently seen on magnified images
      of temporal bone CT studies in children. The cleft may be the fissula ante
      fenestram.

PMID- 14729523
TI  - Diffusion tensor MR imaging visualizes the altered hemispheric fiber connection
      in callosal dysgenesis.
AB  - We report three cases of callosal dysgenesis that were evaluated by diffusion
      tensor imaging and fiber tractography. In partial agenesis of corpus callosum,
      fiber tracts from all regions of brain converged to a partially developed small
      genu portion and connected to the contralateral side. In complete callosal
      agenesis, fibers from the hemispheres failed to cross the midline and formed
      thick bundles running anteroposteriorly (eg, Probst bundle). The thickness of the
      anterior commissure was enlarged or smaller than normal brain, and other white
      matter tracts were not markedly different from normal brain tissue.

PMID- 14729524
TI  - Partial rhombencephalosynapsis.
AB  - We describe an infant in whom partial rhombencephalosynapsis was diagnosed by
      using MR imaging. The anterior vermis and nodulus were normally developed, but
      part of the posterior vermis was deficient. There was partial fusion of the
      hemispheres in the inferior part of the cerebellum. Partial
      rhombencephalosynapsis is described for the first time, and our findings support
      the recent embryologic observations.

PMID- 14729525
TI  - Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and
      diffusion tensor findings.
AB  - Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed
      in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for
      several days. On conventional T2-weighted MR images, symmetric, confluent high
      signal intensity was found in the bilateral thalami, basal ganglia, cortex, and
      subcortical white matter. Diffusion-weighted imaging demonstrated decreased
      apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow
      up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric
      changes, and atrophy, which were most prominent in the occipital lobes. Diffusion
      tensor imaging revealed decreased anisotropy throughout the brain, consistent
      with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and
      diffusion tensor imaging are valuable techniques for the detection of
      irreversible brain damage and for the characterization of hyperintense lesions on
      T2-weighted MR images in patients with the neonatal form of citrullinemia.

PMID- 14729526
TI  - Rapid development of optic glioma in a patient with hybrid phakomatosis:
      neurofibromatosis type 1 and tuberous sclerosis.
AB  - Increased propensity for tumor formation in neurofibromatosis and tuberous
      sclerosis exists because of defective tumor-suppressor genes. Although different
      tumor-suppressor genes may be involved in neurofibromatosis and tuberous
      sclerosis, at the cellular level these genes share rather common enzymatic
      pathways. We believe these genetic malfunctions have resulted in a cumulative or
      additive effect for rapid growth of optic glioma in the following unusual case
      that has hybrid phakomatosis.

PMID- 14729527
TI  - Cerebral Aneurysm Multicenter European Onyx (CAMEO) trial: results of a
      prospective observational study in 20 European centers.
AB  - BACKGROUND AND PURPOSE: This study was designed to investigate the safety and
      efficacy of the Onyx liquid embolic system in treating a selected population of
      patients with intracranial aneurysms that presented difficulties for surgical or
      endovascular alternatives. METHODS: A prospective observational study was
      conducted in 20 European centers enrolling a consecutive series of 119 patients
      with 123 aneurysms judged suitable for Onyx treatment. The series consists of
      findings collected in 97 of 119 patients with 100 of 123 aneurysms, because one
      center declined to provide data to the study sponsor or allow outside audit.
      Clinical and angiographic outcomes were recorded at discharge, 3 months, and 12
      months. All adverse events and re-treatments were recorded. Seventy-nine
      aneurysms were large or giant. RESULTS: Twelve-month follow-up angiography
      findings were available for 71 aneurysms. This angiographic follow-up showed
      complete occlusion in 56 (79%) aneurysms, subtotal occlusion in nine (13%), and
      incomplete occlusion in six (8%). Procedure- or device-related permanent
      neurologic morbidity at final follow-up was present in eight of 97 patients.
      Seven patients died: two deaths were procedure related; one, disease related; and
      four, unrelated causes. Seventy-five of the 82 patients alive and with follow-up
      at 12 months were at Rankin 2 or better status. Delayed occlusion of the parent
      vessel occurred in nine patients; delayed occlusion was asymptomatic in five and
      resulted in permanent neurologic deficit in two. CONCLUSION: In selected patients
      with aneurysms that are unsuitable for coil treatment or in whom previous
      treatment has failed to occlude the aneurysm, Onyx treatment offers an
      endovascular alternative. Aneurysm occlusion rates are superior to reported rates
      of coil occlusion, and treatment morbidity is comparable to that of published
      prospective data on endovascular results for this subgroup of patients.

PMID- 14729528
TI  - Development of gold stents for the treatment of intracranial aneurysms: an
      experimental study in a canine model.
AB  - BACKGROUND AND PURPOSE: Gold has often been used in medicine because of its
      radiopacity and flexibility. To perform stent-supported coil embolization of
      intracranial aneurysms, we prepared a gold stent and examined its flexibility,
      radiopacity, and thrombogenic properties in comparison with a stainless steel
      device implanted in vitro and in vivo. METHODS: Gold stents were prepared by
      plating gold on stainless steel stents as a template. Their mechanical properties
      and trackability in vitro were determined and compared with those of stainless
      steel stents of the same design. Twenty gold stents and two stainless steel
      stents were implanted in canine external carotid, vertebral, and renal arteries,
      as a muscle branch of the maxillary arteries, to examine their performance in
      vivo. RESULTS: The gold stent exhibited much less radial force and greater
      flexibility than the stainless steel stent. It also demonstrated superior
      trackability and radiopacity in the experimental endovascular procedures in
      canines. Histologic examination showed good patency of the stented artery with
      slight endothelial hypertrophy. CONCLUSION: Although there is still room for more
      radial strength, less influence on intimal hypertrophy, a more suitable
      flexibility, and a smoother surface, the superior trackability and radiopacity of
      gold stents seem to support use of this device for the endovascular treatment of
      intracranial aneurysms.

PMID- 14729529
TI  - Aneurysm packing with HydroCoil Embolic System versus platinum coils: initial
      clinical experience.
AB  - The HydroCoil Embolic System (HES; MicroVention, Aliso Viejo, CA) was developed
      to improve the efficacy of endovascular treatment of cerebral aneurysms. The HES
      may reduce recurrences of aneurysms by allowing for increased packing density as
      compared with platinum coils. We report our initial experience with the HES in
      the treatment of 11 patients with cerebral aneurysms and compare findings to
      those in size-matched control cases treated with platinum coils. The HES provided
      substantially improved volumetric packing of the aneurysm lumen relative to
      standard platinum coils (73% vs. 32%; P=.0001).

PMID- 14729530
TI  - Computational simulation of therapeutic parent artery occlusion to treat giant
      vertebrobasilar aneurysm.
AB  - We applied computational fluid dynamics (CFD) analysis to assess 3D digital
      subtraction angiography findings in a patient with a giant vertebrobasilar
      aneurysm to simulate and compare the consequences of left and right vertebral
      artery occlusion. The balloon occlusion test suggested that occlusion of the
      right vertebral artery is the better way to treat this patient's aneurysm from
      the point of view of aneurysmal thrombosis and isolation from the circulation.
      The computer simulation supported this conclusion, at the same time indicating
      that from the point of view of pressure distribution on the wall of the aneurysm,
      the right vertebral occlusion may be also accompanied by an undesirable effect. A
      high-pressure area on the aneurysm wall in systole was revealed. This high
      pressure potentially could lead to subsequent aneurysmal growth, which indeed
      occurred, as was revealed by a follow-up examination 6 months later. This study
      is a good example of possible future applications of CFD in patients with
      cerebrovascular disease before therapeutic intervention.

PMID- 14729531
TI  - Spinal osseous epidural arteriovenous fistula with multiple small arterial
      feeders converging to a round fistular nidus as a target of venous approach.
AB  - We present two patients with spinal epidural arteriovenous fistulas involving the
      vertebral body recruiting dural and osseous branches as feeders. The fistulas,
      forming a round venous sac into which the multiple arterial feeders converge,
      were located near the round bony defect of the vertebral body, suggesting the
      osseous component of this vascular lesion. Transvenous coil embolization of the
      round venous sac results in near-total obliteration of the lesion, leading to
      symptomatic improvement.

PMID- 14729532
TI  - Preoperative embolization for meningeal tumors: evaluation of vascular supply
      with angio-CT.
AB  - When evaluating vascular supply, a combined angiography and CT (angio-CT) system
      provides more accurate vascular anatomy than digital subtraction angiography. To
      the best of our knowledge, however, the application for intracranial tumors has
      not been described. We herein describe a technique of an angio-CT system for
      diagnosis of vascular anatomy of the feeding artery for preoperative embolization
      of meningeal tumors.

PMID- 14729533
TI  - A computer-generated stereotactic "Virtual Subdural Grid" to guide resective
      epilepsy surgery.
AB  - BACKGROUND AND PURPOSE: In selected patients undergoing epilepsy surgery,
      subdural electrode grids play an important role in localizing the epileptogenic
      zone and identifying eloquent cortex. Determining the relationship of the
      electrodes to underlying brain architecture traditionally has been difficult.
      This report describes and validates the use of an original computer-aided method
      that displays a representation of the electrode positions, based on
      postimplantation CT or MR findings, coregistered with a 3D-rendered image of the
      brain, on an image-guided surgery system. METHODS: Seventeen patients underwent
      the procedure with visual verification of the actual and virtual grids undertaken
      during the second (postimplantation) surgery. The accuracy of the Virtual Grid
      electrode positions was further studied in a subgroup of five patients during
      surgery by plotting the distance from the actual electrode positions by using an
      infrared stereotactic probe. RESULTS: The accuracy of the Virtual Grid electrode
      positions by visual inspection was satisfactory in all 17 cases. In the five
      cases in which quantitative measurements were performed, the mean error for the
      CT derived electrode positions was 3.4 mm (range 0.5-5.4) compared with the mean
      error for the MR-derived electrode positions of 2.5 mm (range 0.5-5.2).
      CONCLUSION: The Virtual Grid electrode positions were highly accurate in
      localizing the actual position of the subdural electrodes with both CT- and MR
      derived images. The MR-derived electrodes demonstrated a trend toward better
      accuracy, but the CT images were quicker and easier to process. This technology
      has the potential to minimize both human and technical errors, allowing for a
      more precise tailoring of the cortical resection in epilepsy surgery.

PMID- 14729534
TI  - Improved image quality of intracranial aneurysms: 3.0-T versus 1.5-T time-of
      flight MR angiography.
AB  - BACKGROUND AND PURPOSE: We hypothesize that the nearly doubling of signal-to
      noise ratio at 3.0 T compared with that at 1.5 T yields improved clinical MR
      angiograms and enables superior visualization of intracranial aneurysms. The goal
      of this study was to determine whether 3.0-T time-of-flight (TOF) MR angiography
      is superior to 1.5-T TOF MR angiography in the detection and characterization of
      intracranial aneurysms. METHODS: Fifty consecutive patients referred for MR
      angiography of a known or suspected intracranial aneurysm underwent 3-T TOF MR
      angiography. Seventeen of these 50 patients had also previously undergone 1.5-T
      TOF MR angiography and these images were used as a basis for comparison with
      images obtained at 3.0 T. Fourteen of 23 patients in whom aneurysms were
      identified also underwent prior conventional angiography, which was used as the
      reference standard. Readers blinded to patient history identified the presence
      and location of aneurysm(s) on angiograms and graded images for overall image
      quality by using a five-point scale. RESULTS: Twenty-eight aneurysms were
      identified in 23 of 50 patients. Seventeen aneurysms in 17 patients had been
      documented with 1.5-T MR angiography. The 3.0-T technique had a higher mean image
      quality score than that of the 1.5-T MR technique (P <.0001). Both 3.0-T and 1.5
      T TOF MR angiography depicted all the aneurysms that had been documented by
      conventional angiography. CONCLUSION: 3D TOF MR angiography at 3 T offers
      superior depiction of intracranial aneurysms compared with that of 1.5-T TOF MR
      angiography.

PMID- 14729535
TI  - Prominent laterality of the posterior cerebral artery at three-dimensional time
      of-flight MR angiography in M1-segment middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: Three-dimensional time-of-flight MR angiography (3D TOF
      MRA) often discloses prominent posterior cerebral artery (PCA) laterality in the
      setting of M1-segment middle cerebral artery (MCA) occlusion. We sought to
      analyze the implications of prominent PCA laterality at 3D TOF MRA. METHODS: We
      retrospectively reviewed 3D TOF MRA and digital subtraction angiography (DSA)
      findings in 25 patients (12 male, 13 female; mean age, 68.8 years [age range, 29
      94 years]) with M1-segment occlusion. The observable laterality of the PCA,
      determined on the basis of 3D TOF MRA findings, was scored according to distal
      signal extent and compared with findings of collateral flow from the ipsilateral
      PCA via the leptomeningeal anastomosis (LMA) at DSA. Frequency of PCA laterality
      at 3D TOF MRA in patients and that in 56 healthy control subjects was also
      compared. RESULTS: The positive predictive value of PCA laterality for the
      existence of collateral flow was 99.9% and the negative predictive value 30.7%.
      The distal extent of ipsilateral PCA signal at 3D TOF MRA positively correlated
      with the grade of collateral flow from the PCA via the LMA (r = 0.802; P <.01).
      PCA laterality was significantly less common in control subjects (P <.01).
      CONCLUSION: Prominent PCA laterality at 3D TOF MRA in patients with M1-segment
      occlusion represents the existence of collateral flow from the PCA via the LMA.

PMID- 14729536
TI  - The effect of deafferentation on cerebral blood flow response to acetazolamide.
AB  - BACKGROUND AND PURPOSE: Decreased cerebral blood flow (CBF) response after
      acetazolamide administration may indicate increased cerebral blood volume (CBV)
      owing to reduced perfusion pressure from major cerebral artery steno-occlusive
      disease. However, decreased cerebral metabolic rate of oxygen (CMRO(2)) caused by
      neuronal damage or deafferentation may also decrease the CBF response to
      acetazolamide, which adds complexity to the assessment of autoregulatory
      vasodilatation. The purpose of this study was to investigate the relationship
      between CBF response to acetazolamide and CBV or CMRO(2) in a pure form of
      deafferentation, crossed cerebellar diaschisis (CCD). METHODS: We used positron
      emission tomography to study 17 patients with unilateral supratentorial infarct
      and contralateral cerebellar hypoperfusion. The CBF response to acetazolamide was
      assessed by measuring baseline CBF and CBF 10 minutes after an intravenous
      injection of acetazolamide. Multivariate analysis was used to test the
      independent predictive value of the CBV and CMRO(2) at baseline with respect to
      the change of CBF during acetazolamide administration. RESULTS: Multivariate
      analysis revealed that in CCD CBV was significantly and independently associated
      with the percent change of CBF during acetazolamide administration (P <.0001),
      whereas CMRO(2) was not. CONCLUSION: In deafferentation, changes in CBV may
      account for variations in CBF response to acetazolamide and decreased CMRO(2) may
      not affect CBF response to acetazolamide expressed as the percent change.

PMID- 14729537
TI  - Assessment of the reproducibility of postprocessing dynamic CT perfusion data.
AB  - BACKGROUND AND PURPOSE: Commercially available software programs for the
      conversion of dynamic CT perfusion (CTP) source data into cerebral blood volume
      (CBV), cerebral blood flow (CBF), and mean transit time (MTT) maps require
      operators to subjectively define parameters that are used in subsequent
      postprocessing calculations. Our purpose was to define the variability of CBV,
      CBF, and MTT values derived from CTP maps generated from the same source data
      postprocessed by three different CT technologists (CTTs). METHODS: Raw data
      derived from dynamic CTP examinations performed in 20 subjects were postprocessed
      seven times by three experienced CTTs. Parenchymal regions of interest derived
      from each map (CBV, CBF, and MTT) were compared. The CBF maps generated by each
      technologist were also qualitatively assessed. Decisions made by each analyzer
      during postprocessing were assessed. RESULTS: The intraclass correlation
      coefficients were 0.73 (95% CI, 0.64-0.81), 0.87 (0.83-0.91) and 0.89 (0.85
      0.93), for the CBV, CBF, and MTT parenchymal regions of interest, respectively.
      All individual correlation coefficients between data sets were significant to a P
      value <.05. Measurement error, made solely on the basis of different
      technologists postprocessing the same source data and expressed as the
      coefficients of variation, were 31%, 30%, and 14% for CBV, CBF, and MTT,
      respectively. The selection of the arterial input function (AIF) region of
      interest, venous function region of interest, and preenhancement interval were
      very reproducible. The technologists differed significantly with respect to the
      selection of the postenhancement image (PoEI) (P <.01). A retrospective review of
      the individual CBF maps indicated that variance in the PoEI selection accounted
      for much of the variation in the qualitative appearance of the CBF maps generated
      by different technologists. The PoEI was selected to demarcate the baseline of
      the AIF time-attenuation curve. It is likely that this method of PoEI selection
      significantly contributed to intra- and interanalyzer variability. CONCLUSION:
      There is a high degree of correlation between parenchymal regions of interest
      derived from CBV, CBF, and MTT maps generated from the same dynamic CTP source
      data postprocessed by different operators. The level of agreement, however, may
      not be sufficient to incorporate quantitative values into clinical decision
      making. Quantitative differences between parenchymal regions of interest were not
      infrequently manifest as significant differences in the qualitative appearance of
      the CBF maps. It is likely that, with optimization of postprocessing parameter
      selection, the degree of variability may be substantially reduced.

PMID- 14729538
TI  - Effect of region of interest on interobserver variance in apparent diffusion
      coefficient measures.
AB  - BACKGROUND AND PURPOSE: Apparent diffusion coefficient (ADC) values derived from
      diffusion-weighted MR imaging are useful measurements for assessment of cellular
      alterations in pathologic conditions of the brain. In this study, two
      radiologists independently quantitated ADCs and region-of interest sizes in
      prespecified locations of human brain to test interobserver ADC variance and the
      effect of varying ROI sizes on ADC differences. METHODS: Twenty-seven patients
      with normal MR findings underwent diffusion-weighted imaging (b value = 1000
      s/mm(2)) on a 1.5-T system. Two radiologists independently placed two ROI areas
      of 22 +/- 5 mm(2) and 62 +/- 6 mm(2) (former area inside the latter area) at
      different sites of the brain (centrum semiovale, frontal white matter, nucleus
      caudatus, putamen, thalamus, substantia nigra, red nucleus, and pons) from trace
      images. Differences in ADC measurement obtained from each region of the brain for
      each radiologist and the size of each ROI were compared statistically. RESULTS:
      Mean ADC of prespecified areas of brain ranged between 0.673 and 0.818 mm(2)/s
      x10(-3). Interobserver variance was significant in some of the specified areas
      (centrum semiovale, frontal white matter, pons, substantia nigra, and red
      nucleus). Varying ROI sizes at the pons, substantia nigra, and red nucleus
      yielded statistically different ADC values. CONCLUSION: ADC values are found to
      be unreliable for use in assessing brain disease in some specified areas of the
      brain owing to interobserver variance and different ROI sizes.

PMID- 14729539
TI  - The sphenoparietal sinus of breschet: does it exist? An anatomic study.
AB  - BACKGROUND AND PURPOSE: The termination of the superficial middle cerebral vein
      is classically assimilated to the sphenoid portion of the sphenoparietal sinus.
      This notion has, however, been challenged in a sometimes confusing literature.
      The purpose of the present study was to evaluate the actual anatomic relationship
      existing between the sphenoparietal sinus and the superficial middle cerebral
      vein. METHODS: The cranial venous system of 15 nonfixed human specimens was
      evaluated by the corrosion cast technique (12 cases) and by classic anatomic
      dissection (three cases). Angiographic correlation was provided by use of the
      digital subtraction technique. RESULTS: The parietal portion of the
      sphenoparietal sinus was found to correspond to the parietal portion of the
      anterior branch of the middle meningeal veins. The sphenoid portion of the
      sphenoparietal sinus was found to be an independent venous sinus coursing under
      the lesser sphenoid wing, the sinus of the lesser sphenoid wing, which was
      connected medially to the cavernous sinus and laterally to the anterior middle
      meningeal veins. The superficial middle cerebral vein drained into a
      paracavernous sinus, a laterocavernous sinus, or a cavernous sinus but was never
      connected to the sphenoparietal sinus. All these venous structures were
      demonstrated angiographically. CONCLUSION: The sphenoparietal sinus corresponds
      to the artificial combination of two venous structures, the parietal portion of
      the anterior branch of the middle meningeal veins and a dural channel located
      under the lesser sphenoid wing, the sinus of the lesser sphenoid wing. The
      classic notion that the superficial middle cerebral vein drains into or is
      partially equivalent to the sphenoparietal sinus is erroneous. Our study showed
      these structures to be independent of each other; we found no instance in which
      the superficial middle cerebral vein was connected to the anterior branch of the
      middle meningeal veins or the sinus of the lesser sphenoid wing. The clinical
      implications of these anatomic findings are discussed in relation to dural
      arteriovenous fistulas in the region of the lesser sphenoid wing.

PMID- 14729540
TI  - Sinus pericranii: clinical and imaging findings in two cases of spontaneous
      partial thrombosis.
AB  - Sinus pericranii is an unusual venous anomaly characterized by communication of
      pericranial varicosities with an underlying dural sinus. We report two cases of
      spontaneous partial thrombosis of sinus pericranii presenting as focally tender,
      nonreducible mass lesions different in character from the baseline venous
      abnormality. CT, CT angiography, and CT venography (CTV) were performed in both
      cases. CTV was essential in depicting thrombi within the varicosities. MR (in one
      case) demonstrated the anomaly well, but the thrombus was not evident.
      Conservative therapy was instituted in both cases.

PMID- 14729541
TI  - Management of patients with stunned myocardium associated with subarachnoid
      hemorrhage.
AB  - Cardiac complications are well known after aneurysmal subarachnoid hemorrhage.
      Electrocardiographic changes occur in 50% to 100% of such cases. Arrhythmias,
      left ventricular dysfunction, and frank myocardial infarction are infrequently
      observed. Myocardial infarction must be differentiated from neurogenic stunned
      myocardium, which is a reversible condition. From 1996 to 2001, 105 patients with
      aneurysmal subarachnoid hemorrhage underwent endovascular treatment at the
      University of Michigan. Of these, four patients with no history of cardiac
      disease experienced cardiac failure related to neurogenic stunned myocardium. All
      had signs of left ventricular dysfunction, electrocardiographic changes, and
      elevated cardiac enzymes. Three had pulmonary edema at presentation. All were
      diagnosed with myocardial infarction. One underwent coronary angiography, which
      was normal. All were considered poor surgical candidates and underwent
      endovascular treatment of the aneurysms. Three of four patients developed
      symptomatic vasospasm, and two required balloon angioplasty. Three patients
      achieved good outcomes. The eldest died from severe vasospasm that was
      unresponsive to angioplasty. Reversible cardiac failure associated with
      subarachnoid hemorrhage may be due the neurogenic stunned myocardium. Frequent
      symptomatic vasospasm occurs, possibly related to poor cardiac output and the
      inability to optimize hyperdynamic hypervolemic therapy, particularly with
      compromised volume status. These patients can be treated with endovascular
      therapy of the aneurysms and balloon angioplasty as needed. With aggressive
      management, patients can recover from these reversible cardiac complications.

PMID- 14729542
TI  - Isolated translocation of Wernicke's area to the right hemisphere in a 62-year
      man with a temporo-parietal glioma.
AB  - We describe a case of translocation of temporo-parietal language function
      (Wernicke's area) to the contralateral hemisphere in a right-handed patient with
      a left temporo-parietal glioma. This translocation was identified by functional
      MR imaging (fMRI) and validated by direct cortical stimulation during gross-total
      resection. The current case exemplifies how preoperative fMRI can identify
      unexpected language organization as a result of tumor growth, affording surgery
      to patients who may otherwise be deemed inoperable.

PMID- 14729543
TI  - Erdheim-chester disease mimicking multiple meningiomas syndrome.
AB  - We describe a rare case of non-Langerhans histiocytosis, consistent with Erdheim
      Chester disease (ECD), which presented with lesions resembling multiple
      meningiomas. The patient was initially evaluated for migraine headaches. Initial
      MR imaging demonstrated a parasellar mass and a second mass near the torcula
      considered to represent meningiomas. Within 1 year, he developed bilateral
      orbital lesions surrounding both optic nerves, which were also considered
      meningiomas. Biopsy of one orbital mass revealed a non-Langerhans histiocytosis.
      Subsequently, soft tissue masses, a pericardial effusion, and bone lesions
      consistent with ECD were identified.

PMID- 14729544
TI  - Diffuse leptomeningeal hyperintensity on fluid-attenuated inversion recovery MR
      images in neurocutaneous melanosis.
AB  - Neurocutaneous melanosis (NCM) is a rare neuroectodermal dysplasia characterized
      by large or multiple cutaneous congenital pigmented nevi and benign or malignant
      melanocytic tumors of the leptomeninges. Although the MR manifestations of this
      disease have been reported in a small series of cases, the usefulness of fluid
      attenuated inversion recovery (FLAIR) MR findings has not been documented. We
      present a case of NCM that showed diffuse leptomeningeal hyperintensity on FLAIR
      images. This FLAIR finding may be a clue to the detection of leptomeningeal
      abnormalities in NCM.

PMID- 14729545
TI  - Effect of craniocervical decompression on peak CSF velocities in symptomatic
      patients with Chiari I malformation.
AB  - BACKGROUND AND PURPOSE: Peak CSF velocities detected in individual voxels in the
      subarachnoid space in patients with Chiari I malformations exceed those in
      similar locations in the subarachnoid space in healthy subjects. The purpose of
      this study was to test the hypothesis that the peak voxel velocities are
      decreased by craniocervical decompression. METHODS: A consecutive series of
      patients with symptomatic Chiari I malformations was studied before and after
      craniocervical decompression with cardiac-gated, phase contrast MR imaging.
      Velocities were calculated for each voxel within the foramen magnum at 14 time
      points throughout the cardiac cycle. The greatest velocities measured in a voxel
      during the cephalad and caudad phases of CSF flow through the foramen magnum were
      tabulated for each patient before and after surgery. The differences in these
      velocities between the preoperative and postoperative studies were tested for
      statistical significance by using a single-tailed Student's t test of paired
      samples. RESULTS: Eight patients with a Chiari I malformation, including four
      with a syrinx, were studied. Peak caudad velocity diminished after craniocervical
      decompression in six of the eight patients, and the average diminished
      significantly from 3.4 cm/s preoperatively to 2.4 cm/s postoperatively (P =.01).
      Peak cephalad velocity diminished in six of the eight cases. The average
      diminished from 6.9 cm/s preoperatively to 3.9 cm/s postoperatively, a change
      that nearly reached the significance level of.05 (P =.055). CONCLUSION:
      Craniocervical decompression in patients with Chiari I malformations decreases
      peak CSF velocities in the foramen magnum. The study supports the hypothesis that
      successful treatment of the Chiari I malformation is associated with improvement
      in CSF flow patterns.

PMID- 14729546
TI  - MR imaging features of pigmented villonodular synovitis of the cervical spine.
AB  - Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder
      primarily occurring in the large joints of the appendicular skeleton such as the
      knee and hip joints. We present an unusual case of PVNS involving the cervical
      spine in an adult. MR imaging showed an enhancing mass lesion arising from the
      posterior elements of the cervical spine and hyperintensity on the T2-weighted
      images, without evidence of T2 susceptibility effects. Gross total excision of
      the tumor was performed, and the diagnosis was established by histopathology.

PMID- 14729548
TI  - Diffusion findings in blood clot: the last word?

PMID- 14729549
TI  - The magic measurement.

PMID- 14729550
TI  - Thromboembolic events associated with Guglielmi detachable coil embolization of
      asymptomatic cerebral aneurysms: evaluation of 66 consecutive cases with use of
      diffusion-weighted MR imaging.

PMID- 14729551
TI  - Otic or mythic?

PMID- 14729552
TI  - Persistent otic artery.

PMID- 14729553
TI  - Depression and frailty: the need for multidisciplinary research.

PMID- 14729554
TI  - Delirium in elderly patients.
AB  - Delirium is a mental disorder characterized by disturbances in consciousness,
      orientation, memory, thought, perception, and behavior, of acute onset and
      fluctuating course. It occurs in hyperactive, hypoactive, or mixed forms, in up
      to 50% of elderly hospital inpatients, many with pre-existing dementia, and
      appears to be independently associated with significant increases in functional
      disability, length of hospital stay, rates of admission to long-term care
      institutions, rates of death, and healthcare costs. Despite its clinical
      importance, delirium is often not detected or it is misdiagnosed as dementia or
      other psychiatric illness even though there are potential strategies (e.g.,
      screening by nurses, risk-factor assessment) and instruments that can improve
      detection and diagnosis. Although there has been limited progress in
      understanding the etiology, pathogenesis, assessment, and specific treatment of
      delirium, systematic detection and treatment programs appear to be beneficial for
      elderly surgical patients, as are preventive programs for elderly medical and
      surgical patients. Even now, there is probably enough evidence to recommend
      implementation of these two types of programs in acute-care hospitals.

PMID- 14729555
TI  - The course of depression in elderly patients.
AB  - OBJECTIVE: Studies on the course of major depressive disorder (MDD) among elderly
      persons are limited to short periods of follow-up, seldom provide comparisons
      with younger cohorts, and raise other methodological concerns. METHODS: Utilizing
      15 years of prospective data from the NIMH Collaborative Depression Study, the
      authors examined the index episode of MDD and the time until first observed
      recurrence in those who recovered for subjects in four age-groups defined by age
      at intake: 17-30, 31-50, 51-64, and 65-79 years. Assessments were conducted every
      6 months for 5 years and annually thereafter. Survival analysis examined time
      until recovery and time to first recurrence. RESULTS: Median time-to-recovery was
      similar for the four groups. Median time-to-first recurrence was significantly
      shorter for oldest versus the 51-64-year-old group but not the two other groups.
      The oldest age-group was distinguished from the younger groups by being more
      likely to be divorced/widowed/separated, to have primary depression, and to have
      a history of medical illness, particularly cardiovascular disease or cancer.
      There was no difference in the generally low levels of pharmacotherapy prescribed
      during the index episode or the subsequent well interval. CONCLUSIONS: Elderly
      patients with MDD may have a greater risk of recurrence than younger individuals.
      Low levels of treatment characterize the somatic treatment in all the study
      subjects, regardless of age-group.

PMID- 14729556
TI  - Managing suicide risk in late life: access to firearms as a public health risk.
AB  - OBJECTIVE: The authors assessed the prevalence of gun availability for elderly
      patients to determine whether gun availability is related to the presence of
      suicidal or depressive symptoms. METHODS: This is a cross-sectional epidemiologic
      survey of firearm availability and safety practices. A random sample of older
      adults with a scheduled primary-care clinic appointment was selected and screened
      with the General Health Questionnaire and questions about suicidality and alcohol
      use. Participants were also asked about the availability of firearms in their
      home and about safe gun practices. RESULTS: Of 1,023 patients screened, 285
      (27.9%) reported having some type of firearm in the home, and 202 (19.7%)
      reported having a handgun in the home. Patients with suicidal ideation or high
      levels of depression or psychological distress were not significantly more or
      less likely to have a gun in the home than those without these emotional
      stressors. The strongest predictors of firearm availability were being male and
      being married. CONCLUSIONS: These preliminary data suggest that a significant
      proportion of elderly people have firearms available to them in their homes.
      Those patients with emotional distress did not differ from those without distress
      with respect to having firearms available to them. These data strongly suggest
      the need for screening for firearm availability and education about the safe
      storage of firearms as a potential means of prevention of suicide among elderly
      patients suffering from emotional distress or suicidal ideation.

PMID- 14729557
TI  - Aggression in suicide among adults age 50 and over.
AB  - OBJECTIVE: Aggression confers risk for suicide in younger adults, but there is a
      paucity of research in middle and older adults. The authors examined the link
      between aggression and suicide in individuals age 50 and over. METHODS: Scores on
      general aggression and aggression in the past month were compared in 85 cases and
      85 community-comparison subjects matched on age, gender, race, and county of
      residence. Bivariate and multivariate tests controlling for mood disorders were
      conducted, along with analyses to examine age- or gender-related patterns.
      RESULTS: General aggression distinguished Suicide from Control subjects in men
      and women and in younger (50-64 years) and older (65-plus) subjects. General
      aggression was more strongly related to suicide in individuals under age 65.
      Aggression in the past month was also higher in Suicide than in Control subjects
      from the total sample but was not consistently higher across age and gender
      strata. General aggression and past-month aggression were not associated with
      suicide after controlling for mood disorders. CONCLUSIONS: The association of
      general aggression and suicide extends to middle and older adulthood, and
      aggression may serve as a marker for suicide risk before the onset of depression.

PMID- 14729558
TI  - Using the minimum data set 2.0 mood disturbance items as a self-report screening
      instrument for depression in nursing home residents.
AB  - OBJECTIVE: Seeking to enhance nursing home residents' involvement in their care,
      the authors examined whether the Minimum Data Set, Version 2.0 (MDS) Mood
      Disturbance items could be administered by self-report. They compared the MDS to
      the Geriatric Depression Scale (GDS) in terms of its association with depression
      diagnosis. METHODS: Subjects (N=204) were nursing home residents who were
      interviewed with a psychiatric diagnostic instrument, the GDS, and a self-report
      version of the MDS mood disturbance items. RESULTS: Analyses of variance and
      receiver operating characteristics analyses demonstrated that MDS items
      distinguished subjects with any versus no depression about as well as did the
      GDS. This pattern held within cognitive, gender, and ethnicity subgroups.
      CONCLUSION: The MDS Mood Disturbance items can be reliably and validly
      administered via self-report to persons scoring at least 12 on the Mini-Mental
      State Exam.

PMID- 14729559
TI  - Longitudinal association of initiation/perseveration and severity of geriatric
      depression.
AB  - OBJECTIVE: Many older adults with major depression (MDD) present with impairment
      in initiation and perseveration (IP) tests. However, it remains unclear how these
      abnormalities change during the course of depression. METHODS: The authors
      studied the longitudinal covariation of depression severity and IP functioning in
      157 depressed older adults with MDD. Patients with and without baseline IP
      impairment were studied on three occasions over 1 year. RESULTS: Depression
      severity was associated with concurrent IP scores; however, despite IP
      improvement, those with impaired baseline IP functioning did not reach the level
      of their non-impaired counterparts. CONCLUSION: The persistence of IP
      abnormalities suggests that these patients require careful treatment planning and
      follow-up, given that earlier studies noted an association of abnormal IP with
      disability and poor outcomes of depression treatment.

PMID- 14729560
TI  - Depressive symptoms in elderly patients predict poor adjustment after somatic
      events.
AB  - OBJECTIVE: The authors tested the hypothesis that elderly subjects with premorbid
      depressive symptoms are at increased risk of poor adjustment after a somatic
      event. METHODS: The GLAS study contains a baseline assessment and a follow-up of
      subjects who experienced post-baseline acute myocardial infarction, cancer,
      congestive heart failure, or fall-related injury of the extremities within 5
      years after baseline assessment. Follow-up was conducted at 8 weeks, 6 months,
      and 1 year after the somatic event. Of a baseline sample of 5,279 elderly
      subjects (57 and older), 1,124 subjects who experienced one of the specified
      events were contacted, and sufficient follow-up data were obtained from 558
      subjects. Authors analyzed the course of self-reported physical, role, and social
      functioning, and general health and well-being in subjects without baseline
      limitations. Patients with poor adjustment after the event were compared with
      patients with good adjustment on baseline depressive symptoms. They used logistic
      regression analysis, controlling for several confounders. RESULTS: In
      multivariate analyses, pre-event depressive symptoms were associated with an
      increased risk of poor adjustment in terms of social and role functioning, well
      being, and general health, but not physical functioning. CONCLUSIONS: Elderly
      persons living in the community reporting depressive symptoms are at increased
      risk of poor psychosocial adjustment after a somatic event. Each reported
      baseline depressive symptom was associated with an increased risk of chronic
      decline; this finding stresses the importance of detecting and treating
      depression in community-living elderly persons.

PMID- 14729561
TI  - Holocaust experience and suicidal ideation in high-risk older adults.
AB  - OBJECTIVE: Depression is an identified risk factor for suicidal ideation, a
      precursor for more serious suicidal behaviors. This risk might be further
      compounded in individuals who experience negative life events, including
      traumatic experiences, and those who might have comorbid illnesses. The authors
      examined the impact of past exposure to the Nazi Holocaust on the development of
      suicidal ideation in a sample of depressed older adults. METHODS: Authors
      conducted a retrospective cross-sectional study. The study sample comprised data
      on 530 consecutive eligible first admissions of Jewish patients who were referred
      and admitted to a geriatric psychiatry day hospital program between September
      1986 and December 2000. RESULTS: Multiple logistic-regression analyses,
      controlling for social support, history of suicide attempts, and other negative
      life events, showed that severity of depression and exposure to the Holocaust
      were independently associated with suicidal ideation. Those not showing suicidal
      ideation were slightly more likely to have reported having a confidant.
      CONCLUSIONS: This is the first empirical study to demonstrate an increased
      likelihood for suicidal ideation in survivors of the Nazi Holocaust. The chronic
      stress produced by these traumatic events may have predisposed survivors to cope
      ineffectively as they age, thus resulting in suicidal ideation. Authors highlight
      the importance of a multifaceted approach when assessing suicidal behaviors in
      high-risk groups.

PMID- 14729562
TI  - How the question is asked makes a difference in the assessment of depressive
      symptoms in older persons.
AB  - OBJECTIVE: The authors examined whether older adults respond comparably to two
      standard depression instruments rating symptoms by frequency/duration or degree
      of severity/"bother." METHODS: Data for this cross sectional analysis of a
      prospective cohort came from 699 community-dwelling individuals within the
      communities of Durham, North Carolina, and New Haven, Connecticut. Differences in
      response between the Center for Epidemiological Studies-Depression (CES-D)
      survey, emphasizing symptom frequency, were compared with the Hopkins Symptom
      Checklist (HSCL) subscale, emphasizing bother or discomfort related to those
      symptoms. Socioeconomic, demographic, and clinical characteristics for subjects
      with the greatest difference between standardized scale scores were analyzed with
      multivariable logistic regression. RESULTS: Older persons differed in their
      responses between the two instruments, despite similar content. Individuals in
      the highest quartile of difference between the two scales (indicating more bother
      than symptom frequency) had significantly more education, higher income, and were
      less often African American, with no differences in health conditions. Moreover,
      these specific socioeconomic and ethnic characteristics remained significant in
      multivariable analyses. CONCLUSIONS: Older persons not only differed
      significantly in their responses between depression instruments based on one
      dimension or the other, although with similar content, but response was
      significantly associated with specific subject characteristics. The heterogeneity
      of older patient populations suggests that recognition of depressive symptoms
      should include both constructs of symptom-associated discomfort and symptom
      frequency to achieve more accurate assessment.

PMID- 14729563
TI  - Post-stroke and clinically-defined vascular depression in geriatric
      rehabilitation patients.
AB  - OBJECTIVE: The authors examined the vascular depression hypothesis by comparing
      the frequency of post-stroke depression and clinically-defined vascular
      depression and by examining the relationship between vascular burden and
      depression. METHODS: Data from 670 geriatric rehabilitation patients were
      incorporated to compare the frequency of depression in three patient groups: 1)
      those with no evidence of vascular disease or stroke, 2) those with
      cerebrovascular risk factors (CVRFs) but no evidence of stroke, and 3) patients
      with stroke. They examined the unique relationship between CVRFs and depression
      by use of logistic-regression analysis. RESULTS: Although the frequency of
      depression was not significantly different between stroke (36.4%), CVRF (35.2%),
      and non-vascular patients (28.7%), there was a significant increase in the
      frequency of depression in patients without stroke as CVRF burden increased. This
      effect was not observed among stroke patients. CVRF burden predicted depression
      among patients without stroke even after controlling for general medical
      comorbidity, cognitive functioning, and ADL limitations. CONCLUSIONS: These
      findings provide empirical support for the vascular depression hypothesis and
      also indicate that the rates of clinically-defined vascular depression and post
      stroke depression are similar in geriatric rehabilitation patients.

PMID- 14729564
TI  - Longitudinal support for the relationship between vascular risk factors and late
      life depressive symptoms.
AB  - OBJECTIVE: The authors examined longitudinal support for the vascular depression
      hypothesis by assessing the extent to which baseline vascular burden was
      associated with depressive symptoms 6 and 18 months after discharge from
      inpatient medical rehabilitation. METHODS: One hundred consecutive geriatric
      rehabilitation patients were assessed during their rehabilitation stay and
      subsequently screened for depression 6 and 18 months after discharge. Baseline
      vascular burden was entered into logistic-regression analyses predicting
      depression at 6 and 18 months after controlling for baseline levels of
      depression, general medical burden, limitations in activities of daily living,
      cognitive impairment, and demographic variables including age, education, gender,
      and race. RESULTS: Logistic-regression results demonstrated that, after
      controlling for the covariates described above, baseline vascular burden was
      associated with increased odds of positive depression screens at 6- and 18-month
      follow-up assessments. Furthermore, among patients who were not depressed during
      their rehabilitation stay, vascular burden was predictive of positive depression
      screens at 6- and 18-month follow-up assessments. CONCLUSIONS: Greater vascular
      burden was positively associated with depressive symptoms over time. These
      findings provide further support for the vascular depression hypothesis in late
      life and highlight the need for careful clinical monitoring of this frail group
      of elderly patients.

PMID- 14729565
TI  - Aging and panic disorder: phenomenology, comorbidity, and risk factors.
AB  - OBJECTIVE: The authors compared young and older adults with panic disorder (PD)
      to investigate differences in panic-associated phenomenology, psychiatric
      comorbidity, and risk factors. METHOD: Patients in the older group (age 60 and
      above) were further subdivided into early- and late-onset groups and compared.
      Phenomenology (number of panic symptoms, severity of anxiety, physiological
      symptoms, panic-associated cognitions, and overall severity of PD); comorbidity
      (depressive and anxiety disorders); and risk factors (family history of anxiety
      and life stressors) were assessed in 167 outpatients with PD. RESULTS: Older
      patients reported fewer panic symptoms, less anxiety and arousal, less severe PD,
      lower levels of depression, and higher levels of functioning. Furthermore, within
      the older-patient group, late-onset patients were found to report less distress
      during panic attacks in relation to body sensations and panic-related cognitions
      and emotions. Multiple-regression analysis of the entire sample showed that
      chronological age and age at onset of PD distinctly predicted different domains
      of panic phenomenology. CONCLUSION: PD was consistently less severe in older
      patients across multiple domains, and a later age at onset was associated with
      less distress due to body sensations, cognitions, and emotions during panic
      attacks.

PMID- 14729566
TI  - Self-rated health, depression, and one-year health outcomes in older primary care
      patients.
AB  - OBJECTIVE: The authors tested the hypothesis that poorer self-rated health is
      associated with poorer health outcomes. METHOD: They prospectively examined the
      association of self-rated health to 1-year outcomes in 247 older subjects from
      primary care settings. RESULTS: Poorer self-rated health was independently
      associated with 1-year functional disability, after covarying initial clinical
      and functional measures, but was not independently associated with 1-year
      depression diagnosis. Results were mixed regarding associations with 1-year
      medical burden or mortality. CONCLUSIONS: Clinicians should be vigilant for
      functional decline in patients who perceive their health negatively. Future
      research should test potential mechanisms that might underlie this association.

PMID- 14729567
TI  - Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha)
      regulates triglyceride metabolism by activation of the nuclear receptor FXR.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha)
      has been shown to regulate adaptive thermogenesis and glucose metabolism. Here we
      show that PGC-1alpha regulates triglyceride metabolism through both farnesoid X
      receptor (FXR)-dependent and -independent pathways. PGC-1alpha increases FXR
      activity through two pathways: (1) it increases FXR mRNA levels by coactivation
      of PPARgamma and HNF4alpha to enhance FXR gene transcription; and (2) it
      interacts with the DNA-binding domain of FXR to enhance the transcription of FXR
      target genes. Ectopic expression of PGC-1alpha in murine primary hepatocytes
      reduces triglyceride secretion by a process that is dependent on the presence of
      FXR. Consistent with these in vitro studies, we demonstrate that fasting induces
      hepatic expression of PGC-1alpha and FXR and results in decreased plasma
      triglyceride levels in wild-type but not in FXR-null mice. Our data suggest that
      PGC-1alpha plays an important physiological role in maintaining energy
      homeostasis during fasting by decreasing triglyceride production/secretion while
      it increases fatty acid beta-oxidation to meet energy needs.

PMID- 14729568
TI  - A methylation-mediator complex in hormone signaling.
AB  - The recruitment of coactivators by nuclear hormone receptors (NRs) promotes
      transcription by subverting chromatin-mediated repression. Although the histone
      methylation enzyme CARM1 and an ATP-remodeling complex have been individually
      implicated in nuclear receptor-dependent transcription, neither a functional nor
      mechanistic linkage between these systems has been identified. In the process of
      purifying endogenous CARM1-interacting proteins, we identified an associated
      complex, nucleosomal methylation activator complex (NUMAC), which includes at
      least eight components of SWI/SNF, including the ATPase BRG1. In the NUMAC
      complex, the methylase, CARM1, acquires the ability to covalently modify
      nucleosomal histones, and the directed nucleosome versus free core histone
      methylation-specificity change is increased dramatically. Reciprocally, CARM1
      stimulates the ATPase activity of BRG1, a key component in nucleosome remodeling.
      In vivo, CARM1 and BRG1 coassemble on an estrogen receptor (ER)-target gene to
      cooperatively activate ER-dependent transcription. This association of ATP
      remodeling factors with HMT CARM1 defines a new component of regulation in the
      nuclear hormone-signaling pathway.

PMID- 14729569
TI  - p63 is the molecular switch for initiation of an epithelial stratification
      program.
AB  - Development of stratified epithelia, such as the epidermis, requires p63
      expression. The p63 gene encodes isoforms that contain (TA) or lack (DeltaN) a
      transactivation domain. We demonstrate that TAp63 isoforms are the first to be
      expressed during embryogenesis and are required for initiation of epithelial
      stratification. In addition, TAp63 isoforms inhibit terminal differentiation,
      suggesting that TAp63 isoforms must be counterbalanced by DeltaNp63 isoforms to
      allow cells to respond to signals required for maturation of embryonic epidermis.
      Our data demonstrate that p63 plays a dual role: initiating epithelial
      stratification during development and maintaining proliferative potential of
      basal keratinocytes in mature epidermis.

PMID- 14729570
TI  - The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from
      the lin-41 3'UTR.
AB  - Caenorhabditis elegans let-7, a founding member of the microRNA family, is
      predicted to bind to six sites in the 3'UTR of the mRNA of its target gene, lin
      41, to down-regulate LIN-41. Here, we demonstrate that wild-type let-7 microRNA
      binds in vitro to RNA from the lin-41 3'UTR. This interaction is dependent on two
      conserved let-7 complementary sites (LCSs). A 27-nucleotide sequence between the
      LCSs is also necessary for down-regulation in vivo. LCS mutations compensatory to
      the lesion in let-7(n2853) can partially restore lin-41 3'UTR function in a let
      7(n2853) background, providing the first experimental evidence for an animal
      miRNA binding directly to its validated target in vivo.

PMID- 14729571
TI  - A pre-ribosome-associated HEAT-repeat protein is required for export of both
      ribosomal subunits.
AB  - Rrp12p (Ypl012w) is unusual among characterized ribosome synthesis factors in
      being associated with late precursors to both the 40S and 60S subunits. Rrp12p is
      predominantly nuclear with nucleolar enrichment at steady state, but shuttled
      between the nucleus and cytoplasm in a heterokaryon assay. Strains depleted of
      Rrp12p are impaired in the nuclear export of both ribosomal subunits. Sequence
      analysis combined with fold recognition and modeling showed that Rrp12p is a
      member of a family of pre-ribosome-associated HEAT-repeat proteins. Like other
      HEAT-repeat transport factors, Rrp12p binds in vitro to nucleoporin FG-repeats of
      both the GLFG and FXFG families and to the GTPase Gsp1p (yeast RAN). Rrp12p also
      showed robust in vitro binding to a pre-rRNA transcript, in addition to poly(A)
      and poly(U). We propose that Rrp12p binds to the RNA components of the pre
      ribosomes and promotes export of both subunits via its interactions with the
      nucleoporins and Gsp1p.

PMID- 14729573
TI  - A bZIP/bRLZ transcription factor required for DIF signaling in Dictyostelium.
AB  - The intermingled differentiation and sorting out of Dictyostelium prestalk-O and
      prespore cells requires the diffusible signaling molecule DIF-1, and provides an
      example of a spatial information-independent patterning mechanism. To further
      understand this patterning process, we used genetic selection to isolate mutants
      in the DIF-1 response pathway. The disrupted gene in one such mutant, dimA(-),
      encodes a bZIP/bRLZ transcription factor, which is required for every DIF-1
      response investigated. Furthermore, the dimA(-) mutant shows strikingly similar
      developmental defects to the dmtA(-) mutant, which is specifically defective in
      DIF-1 synthesis. However, key differences exist: (1) the dmtA(-) mutant responds
      to DIF-1 but does not produce DIF-1; (2) the dimA(-) mutant produces DIF-1 but
      does not respond to DIF-1; and (3) the dimA(-) mutant exhibits cell autonomous
      defects in cell type differentiation. These results suggest that dimA encodes the
      key transcriptional regulator required to integrate DIF-1 signaling and
      subsequent patterning in Dictyostelium.

PMID- 14729572
TI  - A glutamate receptor-interacting protein homolog organizes muscle guidance in
      Drosophila.
AB  - During Drosophila embryogenesis, developing muscles extend growth-cone-like
      structures to navigate toward specific epidermal attachment sites. Here, we show
      that the homolog of Glutamate Receptor-Interacting Proteins (DGrip) acts as a key
      component of proper muscle guidance. Mutations in dgrip impair patterning of
      ventral longitudinal muscles (VLMs), whereas lateral transverse muscles (LTMs)
      that attach to intrasegmental attachment sites develop normally. Myoblast fusion,
      stabilization of muscle contacts, and general muscle function are not impaired in
      the absence of DGrip. Instead, the proper formation of cellular extensions during
      guidance fails in dgrip mutant VLMs. DGrip protein concentrates at the ends of
      VLMs while these muscles guide toward segment border attachment sites.
      Conversely, LTMs overexpressing DGrip form ectopic cellular extensions that can
      cause attachment of these muscles to other muscles at segment borders. Our data
      suggest that DGrip participates in the reception of an attractive signal that
      emanates from the epidermal attachment sites to direct the motility of developing
      muscles. This dgrip phenotype should be valuable to study mechanistic principles
      of Grip function.

PMID- 14729574
TI  - Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells
      during zebrafish gastrulation.
AB  - The large extracellular polysaccharide Hyaluronan (HA) and its synthesizing
      enzymes (Has) have been implicated in regulating the migratory potential of
      metastatic cancer cells. Here, we analyze the roles of zebrafish Has2 in normal
      development. Antisense morpholino oligonucleotide (MO)-mediated knockdown of
      zebrafish Has2 leads to the loss of HA, and severe migratory defects during
      gastrulation, somite morphogenesis and primordial germ cell migration. During
      gastrulation, ventrolateral cells of has2 morphant embryos fail to develop
      lamellipodia and to migrate dorsally, resulting in a blockage of dorsal
      convergence, whereas extension of the dorsal axis is normal. The effect is cell
      autonomous, suggesting that HA acts as an autocrine signal to stimulate the
      migration of HA-generating cells. Upon ectopic expression in axial cells, has2
      causes the formation of supernumerary lamellipodia and a blockage of axis
      extension. Epistasis analyses with constitutively active and dominant-negative
      versions of the small GTPase Rac1 suggest that HA acts by Rac1 activation, rather
      than as an essential structural component of the extracellular matrix. Together,
      our data provide evidence that convergence and extension are separate
      morphogenetic movements of gastrulation. In addition, they suggest that the same
      HA pathways are active to auto-stimulate cell migration during tumor invasion and
      vertebrate embryogenesis.

PMID- 14729575
TI  - Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin
      independent process.
AB  - The signalling molecule Hedgehog (Hh) functions as a morphogen to pattern a field
      of cells in animal development. Previous studies in Drosophila have demonstrated
      that Tout-velu (Ttv), a heparan sulphate polymerase, is required for Hh movement
      across receiving cells. However, the molecular mechanism of Ttv- mediated Hh
      movement is poorly defined. We show that Dally and Dally-like (Dly), two
      Drosophila glypican members of the heparan sulphate proteoglycan (HSPG) family,
      are the substrates of Ttv and are essential for Hh movement. We show that embryos
      lacking dly activity exhibit defects in Hh distribution and its subsequent
      signalling. However, both Dally and Dly are involved and are functionally
      redundant in Hh movement during wing development. We further demonstrate that Hh
      movement in its receiving cells is regulated by a cell-to-cell mechanism that is
      independent of dynamin-mediated endocytosis. We propose that glypicans transfer
      Hh along the cell membrane to pattern a field of cells.

PMID- 14729576
TI  - Navigation of trochlear motor axons along the midbrain-hindbrain boundary by
      neuropilin 2.
AB  - Trochlear motor axons project dorsally along the midbrain-hindbrain boundary
      (MHB) to decussate at the dorsal midline. We report on the roles of neuropilin 2
      and its ligands in the molecular mechanisms controlling this trajectory. In chick
      embryos, neuropilin 2 was expressed in the neuroepithelium of the dorsal isthmus
      in addition to the trochlear neurons, and Sema3F transcripts were localized along
      the caudal margin of the midbrain. Misexpression of Sema3F demonstrated that
      Sema3F displays repulsive activity in vivo that guides the trochlear motor axons
      along the MHB. An unexpected result was that misexpression of neuropilin 2
      canceled the midbrain-evoked repulsion, allowing trochlear motor axons to cross
      the MHB and invade the tectum. A binding assay with neuropilin 2 ectodomain
      revealed the existence of neuropilin 2 ligands in the midbrain, which were masked
      by ectopic neuropilin 2. We therefore propose that neuropilin 2 neutralizes the
      repulsive activity in order to steer trochlear motor axons towards the dorsal
      decussation point. Taken together, our results suggest that the interaction of
      neuropilin 2 with its ligands has crucial roles for establishing trochlear
      trajectory along the MHB.

PMID- 14729577
TI  - SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis.
AB  - During development, hematopoiesis initiates in the yolk sac through a process
      that depends on VEGF/Flk1 signaling and on the function of the SCL/Tal1
      transcription factor. Here we show that VEGF modifies the developmental potential
      of primitive erythroid progenitors and prolongs their life span. Furthermore, the
      survival of yolk sac erythrocytes in vivo depends on the dose of VEGF.
      Interestingly, in Vegf(lo/lo) embryos carrying a hypomorph allele, Flk1-positive
      cells reach the yolk sac at E8.5, but are severely compromised in their ability
      to generate primitive erythroid precursors. These observations indicate that
      during embryonic development, different thresholds of VEGF are required for the
      migration and clonal expansion of hematopoietic precursors. The near absence of
      primitive erythroid precursors in Vegf(lo/lo) embryos correlates with low levels
      of Scl in the yolk sac. Strikingly, gain-of-function of SCL partially complements
      the hematopoietic defect caused by the hypomorph Vegf(lo) allele, and re
      establishes the survival of erythroid cells and the expression of erythroid genes
      (Gata1 and betaH1). This indicates that SCL functions downstream of VEGF to
      ensure an expansion of the hematopoietic compartment.

PMID- 14729578
TI  - The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by
      parathyroid hormone and calcium: implications for prostate cancer chemoprevention
      by vitamin D.
AB  - The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D [1
      alpha,25(OH)(2)D] promotes the differentiation and inhibits the proliferation,
      invasiveness and metastasis of prostate cells. However, 1 alpha,25(OH)(2)D is not
      suitable as a chemopreventive agent because its administration can cause
      hypercalcemia. Serum levels of 1 alpha,25(OH)(2)D are tightly regulated by the
      renal enzyme, 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), which
      synthesizes 1 alpha,25(OH)(2)D from the prohormone, 25-hydroxyvitamin D
      [25(OH)D]. Normal prostate epithelial cells in primary culture, as well as
      several prostate cancer cell lines, also express 1 alpha-OHase and synthesize the
      hormone intracellularly. We now investigated the regulation of the prostate 1
      alpha-OHase by the three most important regulators of the renal 1 alpha-OHase:
      calcium, 1 alpha,25(OH)(2)D and parathyroid hormone (PTH). The 1 alpha-OHase
      activity in the primary cultures of prostate epithelial cells was inhibited by 1
      alpha,25(OH)(2)D(3) at 10 and 100 nM, whereas PTH at 10 and 100 nM had no
      significant effect. Calcium at 1.2 and 2.4 mM had no significant effect on the
      enzyme activity in the PZ-HPV-7 cell line, a prostate epithelial cell line
      derived from normal prostate tissue. Conversely, 1.2 or 2.4 mM calcium markedly
      inhibited 1 alpha-OHase activity in a human kidney cell line used as a positive
      control. Furthermore, PTH at 100 nM and calcium at 1.2 and 2.4 mM had no effect
      on the 1 alpha-OHase gene promoter activity in prostate cells, whereas the
      promoter activity was inhibited 48 +/- 5% by 100 nM 1 alpha,25(OH)(2)D(3). Our
      findings suggest that, unlike the renal enzyme, the prostate 1 alpha-OHase
      appears to be largely unregulated by serum levels of PTH and calcium. These
      findings support the hypothesis that vitamin D or 25(OH)D may be useful as
      chemopreventive agents for prostate cancer because their administration should
      cause an increased synthesis of 1 alpha,25(OH)(2)D within prostate cells.

PMID- 14729579
TI  - Heparin/heparan sulfate interacting protein plays a role in apoptosis induced by
      anticancer drugs.
AB  - Heparin/heparan sulfate interacting protein (HIP, also known as ribosome protein
      L29) is involved in cell-cell and cell-extracellular matrix interactions and
      influences cell proliferation, migration and differentiation. In the present
      study, we investigated the role of HIP in anticancer drug-induced apoptosis. Both
      colon cancer HCT-116 and HT-29 cells showed dose-dependent down-regulation of HIP
      expression when treated with sodium butyrate. The down-regulation was negatively
      correlated with the percentage of apoptotic cells (R = -0.955, P = 0.03 and R = 
      0.792, P = 0.06 for HCT-116 and HT-29 cells, respectively). The correlation
      between HIP expression and apoptosis in HCT-116 cells was also evident in the
      differential expression of HIP in the floating and adherent cell populations.
      Most apoptotic cells were distributed in the floating population. HIP expression
      in this population was approximately 30% lower than adherent and untreated
      control cells. HIP expression in HCT-116 cells was also significantly decreased
      in parallel with apoptosis after treatment with 50 micro M camptothecin and 20
      micro M 5-fluorouracil. This indicates that the down-regulation of HIP may be a
      general phenomenon in anticancer drug-induced apoptosis. The down-regulation of
      HIP occurred in the early phase of apoptosis, in parallel with the activation of
      caspase-3 and the externalization of phosphatidylserine. The functional
      significance of HIP in apoptosis was shown by knocking down the expression of HIP
      using small interfering RNA. A 50% reduction in HIP expression was sufficient to
      increase the percentage of apoptotic cells (from 11 to 20%) and increase the
      sensitivity of the cells to apoptosis induced by 1 mM butyrate by 60%. These
      results indicate that HIP may play an important role in anticancer drug-induced
      apoptosis.

PMID- 14729580
TI  - Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental
      exposures and bladder cancer risk.
AB  - Tobacco smoking and occupational exposure are major risk factors of bladder
      cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic
      amines, which lead to oxidative stress and DNA damage. Several enzymes, which
      play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase
      (MPO) produces a strong oxidant for microbicidal activity, and activates
      carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the
      methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone
      oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds,
      which also protects cells from redox cycling. Manganese superoxide dismutase
      (MnSOD) protects cells from free radical injury. To test the hypothesis that the
      risk of bladder cancer can be influenced by polymorphisms in the genes that
      modulate oxidative stress, in particular by interacting with environmental
      carcinogens, we conducted a hospital-based case-control study among men in
      Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214
      controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines
      were coded blindly by occupational physicians. Unconditional multivariate
      logistic regression was applied to model the association between genetic
      polymorphisms and bladder cancer risk and the effect of modifications of smoking
      and occupational exposures were evaluated. MPO G-463A homozygous variant was
      associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI =
      0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR
      of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR =
      7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02, 95% CI = 1.35-6.74). We did not
      observe an effect of COMT Val108Met polymorphism. These findings suggest that
      individual susceptibility of bladder cancer may be modulated by MPO and MnSOD
      polymorphisms, and that the combination of genetic factors involved in oxidative
      stress response with environmental carcinogens may play an important role in
      bladder carcinogenesis.

PMID- 14729581
TI  - Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than
      benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive
      tract.

PMID- 14729582
TI  - Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3
      b]indole (MeAalphaC) in recombinant test systems expressing human xenobiotic
      metabolizing enzymes.
AB  - 2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and some metabolites were
      investigated for mutagenicity in mammalian cell lines and bacterial strains
      engineered for the expression of human enzymes. MeAalphaC induced gene mutations
      (studied at the hprt locus) in Chinese hamster V79-derived cells co-expressing
      cytochrome (CYP) 1A2 and sulphotransferase (SULT) 1A1 even at a concentration of
      30 nM, but was inactive in cells co-expressing CYP1A2 and N-acetyltransferase
      (NAT) 1 or 2. MeAalphaC, tested in the presence of rat liver post-mitochondrial
      fraction, showed strongly enhanced mutagenicity in a Salmonella typhimurium
      strain expressing human SULT1A1 compared with the control (recipient) strain
      TA1538/1,8-DNP (deficient in endogenous acetyltransferase). Mutagenicity was also
      enhanced, although to a lesser extent, when NAT2 was expressed in the latter
      strain. The metabolite, 2-hydroxylamino-3-methyl-9H-pyrido[2,3-b]indole (N-OH
      MeAalphaC) was a direct mutagen to strains TA1538 and TA1538/ 1,8-DNP. This
      mutagenicity was strongly enhanced in corresponding strains expressing SULT1A1. A
      moderate enhancement was observed when SULT1A2, SULT1B1, SULT1C2 or NAT2 were
      expressed in strain TA1538. The remaining enzymes studied (SULT1A3, 1C1, 1E1,
      2A1, 2B1a, 2B1b, 4A1 and NAT1) did not indicate any activation of N-OH-MeAalphaC.
      Preliminary mutagenicity experiments in SULT-expressing S.typhimurium strains
      were conducted with other hydroxylated metabolites of MeAalphaC. The phenols, 6-
      and 7-hydroxy-MeAalphaC, were inactive under the conditions studied. The benzylic
      alcohol, 2-amino-3-hydroxymethyl-9H-pyrido[2,3-b]indole, was mutagenic in a
      strain expressing SULT1A1, but its activity was much weaker than that of N-OH
      MeAalphaC. Thus, N-hydroxylation (e.g. mediated by CYP1A2) and sulpho conjugation
      (primarily mediated by SULT1A1) was the dominating activation pathway of
      MeAalphaC in model systems engineered for human enzymes. Some other SULT forms as
      well as NAT2 were also capable of activating N-OH-MeAalphaC, although with much
      lower efficiency than SULT1A1. Another minor activation pathway involved benzylic
      hydroxylation followed by sulpho conjugation by SULT1A1.

PMID- 14729583
TI  - Celecoxib inhibits phorbol ester-induced expression of COX-2 and activation of AP
      1 and p38 MAP kinase in mouse skin.
AB  - Celecoxib, the first US FDA-approved selective cyclooxygenase-2 (COX-2) inhibitor
      initially developed for the treatment of adult rheumatoid arthritis and
      osteoarthritis, was reported to reduce the polyp burden in patients with familial
      adenomatous polyposis. This specific COX-2 inhibitor also protects against
      experimentally induced carcinogenesis, but molecular mechanisms underlying its
      chemopreventive activities remain largely unresolved. In the present work, we
      found that celecoxib inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      expression of COX-2 in female ICR mouse skin when applied topically 30 min prior
      to TPA as determined by both immunoblot and immunohistochemical analyses. In
      another study, celecoxib attenuated the DNA binding activity of activator protein
      1 (AP-1) through suppression of c-Jun and c-Fos expression in TPA-treated mouse
      skin. In addition, celecoxib inhibited both the catalytic activity and
      phosphorylation of p38 mitogen-activated protein (MAP) kinase. In the same animal
      model, TPA treatment resulted in rapid activation via phosphorylation of
      extracellular signal-regulated protein kinase (ERK)1/2 and p38 MAP kinase, which
      are upstream of AP-1 in mouse skin. In order to clarify the roles of p38 and ERK
      in TPA-induced AP-1 activation, we utilized the pharmacologic inhibitors of these
      enzymes. The p38 inhibitor SB203580 blocked TPA-mediated AP-1 activation, while
      the MEK1/2 inhibitor U0126 was not inhibitory despite suppression of c-Fos
      expression in mouse skin. Furthermore, SB203580 markedly inhibited COX-2
      expression induced by TPA. Taken together, these findings suggest that celecoxib
      down-regulates COX-2 by blocking activation of p38 MAP kinase and AP-1, which may
      represent molecular mechanisms underlying antitumor promoting effects of this
      drug on mouse skin tumorigenesis.

PMID- 14729584
TI  - Colorectal cancer without high microsatellite instability and chromosomal
      instability--an alternative genetic pathway to human colorectal cancer.
AB  - At least two forms of genomic instability have been described in colorectal
      cancers (CRCs): microsatellite instability (MIN), which is characterized by a
      high frequency of microsatellite instability (MSI-H) and chromosomal instability
      (CIN), which is characterized by losses and gains of chromosomes (aneuploidy), as
      well as chromosome rearrangements. Morphological and molecular heterogeneity
      within MIN(-) CRCs have been described, but the distinctions between MIN(-)
      tumors with CIN and those without CIN remain largely unknown. We studied 179
      colorectal cancers to elucidate the clinicopathological characteristics and
      molecular events in CRCs arising along these pathways. Loss of heterozygosity,
      MIN, DNA content, mutation of p53 and K-ras, and expression of p53, hMLH1 and
      hMSH2 were examined. We found that a subtype of tumors (17%) with MIN(-) and CIN(
      ), differed from MIN(-)CIN(+) tumors with respect to clinicopathological and
      genetic characteristics. This subtype was associated with a greater frequency of
      poorly differentiated and/or mucinous tumors (26%). This subtype of tumors had an
      extremely low p53 gene mutation rate (11%) and a relatively high p53 protein
      accumulation rate (55%). The dissociation between the p53 gene mutation and
      protein accumulation suggests that stabilization of p53 protein in the absence of
      p53 gene mutation may be an important event on a distinct pathway.

PMID- 14729585
TI  - The E-cadherin -347G->GA promoter polymorphism and its effect on transcriptional
      regulation.
AB  - E-cadherin plays a critical role in epithelial cell-cell adhesion and maintenance
      of tissue architecture. Loss of E-cadherin expression in humans has been
      associated with cancer, and a number of cancer-related mutations have been
      identified. Here, we sought to investigate whether the -347G-->GA single
      nucleotide polymorphism affects the transcriptional activity of the E-cadherin
      gene. First, we measured the promoter activity of the -347G-->GA polymorphism
      using a dual luciferase reporter assay and electrophoretic mobility shift assay
      (EMSA). The dual luciferase reporter assay showed that the GA allele decreased
      the transcriptional efficiency by 10-fold (P < 0.001) compared with the G allele.
      Similarly, EMSA revealed that the GA allele had a weak transcription factor
      binding strength compared with the G allele. We then examined the frequency of
      this polymorphism in familial gastric cancer (FGC) patients by denaturing high
      performance liquid chromatography. We found that the E-cadherin genotype (
      347G/GA heterozygous or GA homozygous) was associated with FGC patients (P <
      0.05) compared with the G homozygous genotype. Taken together, these results
      suggest that the GA allele may cause weak transcription factor binding affinity
      and low transcriptional activity in E-cadherin expression.

PMID- 14729586
TI  - A proteomic study of resistance to deoxycholate-induced apoptosis.
AB  - The development of apoptosis resistance appears to be an important factor in
      colon carcinogenesis. To gain an understanding of the molecular pathways altered
      during the development of apoptosis resistance, we selected three cell lines for
      resistance to induction of apoptosis by deoxycholate, an important etiologic
      agent in colon cancer. We then evaluated gene expression levels for 825 proteins
      in these resistant lines, compared with a parallel control line not subject to
      selection. Eighty-two proteins were identified as either over-expressed or under
      expressed in at least two of the resistant lines, compared with the control.
      Thirty-five of the 82 proteins (43%) proved to have a known role in apoptosis. Of
      these 35 proteins, 21 were over-expressed and 14 were under-expressed. Of those
      that were over-expressed 18 of 21 (86%) are anti-apoptotic in some circumstances,
      of those that were under-expressed 11 of 14 (79%) are pro-apoptotic in some
      circumstances. This finding suggests that apoptosis resistance during selection
      among cultured cells, and possibly in the colon during progression to cancer, may
      arise by constitutive over-expression of multiple anti-apoptotic proteins and
      under-expression of multiple pro-apoptotic proteins. The major functional groups
      in which altered expression levels were found are post-translational modification
      (19 proteins), cell structure (cytoskeleton, microtubule, actin, etc.) (17
      proteins), regulatory processes (11 proteins) and DNA repair and cell cycle
      checkpoint mechanisms (10 proteins). Our findings, overall, bear on mechanisms by
      which apoptosis resistance arises during progression to colon cancer and suggest
      potential targets for cancer treatment. In addition, assays of normal-appearing
      mucosa of colon cancer patients, for over- or under-expression of genes found to
      be altered in our resistant cell lines, may allow identification of early
      biomarkers of colon cancer risk.

PMID- 14729587
TI  - Polycyclic aromatic hydrocarbons induce both apoptotic and anti-apoptotic signals
      in Hepa1c1c7 cells.
AB  - In this study we show that benzo[a]pyrene (B[a]P) and the cyclopenta polycyclic
      aromatic hydrocarbons (CP-PAH) cyclopenta[c,d]pyrene (CPP), benz[j]aceanthrylene
      (B[j]A) and benz[l]aceanthrylene (B[l]A) induce apoptosis in Hepa1c1c7 cells, as
      measured by fluorescence microscopy and flow cytometry. The compounds induced
      formation of the active form of caspase-3, cleavage of its intracellular
      substrate, poly(ADP-ribose)polymerase (PARP), and DNA fragmentation. B[j]A was
      found to be the most potent in inducing apoptosis, followed by B[a]P, CPP and
      B[l]A. All compounds increased expression of CYP1A1 with relative potencies B[j]A
      > B[a]P >> CPP > B[l]A, corresponding well with their relative apoptotic
      responses. alpha-Naphthoflavone (alphaNF), an inhibitor of CYP1A1, reduced the
      induced apoptosis. B[a]P and CP-PAH exposure also resulted in an accumulation of
      the tumour suppressor protein p53. No changes were observed in the protein levels
      of Bax and Bcl-2, whereas the anti-apoptotic Bcl-xl protein was down-regulated,
      as judged by western blot analysis. Fluorescence microscopic analysis revealed a
      translocation of p53 to the nucleus and of Bax to the mitochondria. Furthermore,
      caspase-8 was activated and Bid cleaved. Interestingly, the levels of anti
      apoptotic phospho-Bad (Ser155 and Ser112) had a biphasic increase after B[a]P or
      CPP treatment. Whereas alphaNF markedly reduced the activation of B[a]P to
      reactive metabolites, as measured by covalent binding to macromolecules, it did
      not inhibit the up-regulation of phospho-Bad. Neither of the compounds triggered
      apoptosis in primary cultures of rat lung cells (Clara cells, type 2 cells and
      lung alveolar macrophages), possibly due to a lack of CYP1A1 induction. In
      conclusion, B[a]P and the CP-PAH induced apoptotic as well as anti-apoptotic
      signals in Hepa1c1c7 cells.

PMID- 14729588
TI  - In silico p53 mutation hotspots in lung cancer.
AB  - For cancer one of the primary aims of molecular epidemiology is to identify the
      endogenous or exogenous cause of mutations within a gene. Regarding exogenous
      mutagens, many mutation data have become available via in vitro and in vivo
      mutation assays and become publicly available through mutation databases such as
      the Mammalian Gene Mutation Database (http://lisntweb.swan.ac.uk/cmgt/index.htm).
      One particular mutation assay incorporates the bacterial supF tRNA gene which
      allows selection of mutations at virtually all nucleotides. We have developed an
      algorithm called LwPy53 that utilizes mutation data from supF that can be used to
      predict chemically induced hot-spots along the p53 gene. The prediction is based
      on a number of parameters: the mutability of supF dinucleotides after treatment
      with a mutagen of interest; DNA curvature along the p53 gene; the selectability
      of a mutation along the gene; the likelihood of a site being within a nucleosome.
      We applied LwPy53 to exons 5, 7 and 8 of p53 using benzo[a]pyrene diol epoxide
      (BPDE)-induced mutation data for supF to obtain a predicted BPDE G-->T
      transversion spectrum after hypothetical treatment with BPDE. The resulting
      predicted mutation distribution reveals strong mutation hot-spots at codons 157,
      248 and 273 that correlate with known BPDE adduct hot-spots within p53. The
      predicted BPDE spectrum strongly resembles the G-->T mutation spectrum compiled
      from known lung cancer mutation data from smokers and further supports evidence
      that BPDE contributes to the overall smoking-related mutation distribution in
      lung cancer. The algorithm shows how BPDE target sequence specificity and DNA
      curvature both shape the overall mutation distribution.

PMID- 14729589
TI  - Cell type-specific methylation of an intronic CpG island controls expression of
      the MCJ gene.
AB  - Over 50% of human genes are associated with CpG islands and DNA methylation
      within such CpG islands has been clearly correlated with inhibition of
      expression. Whereas changes in DNA methylation play a key role in a number of
      human diseases, in particular cancer, in normal DNA CpG islands are nearly always
      methylation free, regardless of the expression status of the associated gene.
      Only limited evidence supports a role for DNA methylation in controlling tissue
      specific expression in adult somatic tissue. Loss of expression of the MCJ gene
      has previously been linked to increased chemotherapeutic drug resistance in
      ovarian cancer. We report that loss of expression of MCJ in drug-resistant
      ovarian cancer cell lines depends on methylation of a CpG island within its first
      exon, but is independent of methylation within the promoter region. Furthermore,
      cell type-specific expression of the MCJ gene in normal cells also depends on the
      methylation status of the CpG island within its first exon. The MCJ CpG island is
      methylated and the gene is not expressed in cells of epithelial origin, but
      unmethylated and expressed in cells of lymphocyte or fibroblast origin. Chromatin
      immunoprecipitation assays determined that MCJ CpG island methylation was
      associated with loss of histone acetylation in ovarian epithelial cells compared
      with unmethylated fibroblast cells. Reduced acetylation was observed not only
      within the CpG island, but also within the promoter region, suggesting that CpG
      island methylation may direct alterations in chromatin structure within the
      promoter region, leading to gene inactivation.

PMID- 14729590
TI  - Prepubertal estradiol and genistein exposures up-regulate BRCA1 mRNA and reduce
      mammary tumorigenesis.
AB  - Prepubertal exposure to soy or its biologically active component genistein
      reduces later breast cancer risk in both animal models and human populations. We
      investigated whether that might be due to reported estrogenic properties of
      genistein. Our study indicated that daily prepubertal exposures between postnatal
      days 7 and 20 to 10 microg 17beta-estradiol (E2) reduced later risk of developing
      7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Assessment of
      mammary gland morphology revealed that both prepubertal E2 and genistein (50
      microg daily) exposures reduced the size of mammary epithelial area and number of
      terminal end buds (TEBs) and increased the density of lobulo-alveolar structures,
      suggesting that these exposures induced elimination of targets for malignant
      transformation by differentiation. Next, the mechanisms mediating the protective
      effects of E2 and genistein were investigated. E2 is shown to up-regulate BRCA1,
      a tumor suppressor gene that participates in DNA damage repair processes and cell
      differentiation and that down-regulates the activity of estrogen receptor (ER)
      alpha. The expression of BRCA1 mRNA was up-regulated in the mammary glands of
      rats exposed to E2 or genistein during prepuberty, when determined at the ages of
      3, 8 and 16 weeks. Prepubertal E2 exposure reduced ER-alpha levels in the mammary
      gland, while prepubertal genistein exposure had an opposite effect. Our results
      suggest that prepubertal estrogenic exposures may reduce later breast cancer risk
      by inducing a persistent up-regulation of BRCA1 in the mammary gland.

PMID- 14729591
TI  - Genetic polymorphisms in DNA repair genes and possible links with DNA repair
      rates, chromosomal aberrations and single-strand breaks in DNA.
AB  - We analysed the associations between genetic polymorphisms in genes coding for
      DNA repair enzymes XPD (exon 23 A --> C, K751Q), XPG (exon 15 G --> C, D1104H),
      XPC (exon 15 A --> C, K939Q), XRCC1 (exon 10 G --> A, R399Q) and XRCC3 (exon 7 C 
      -> T, T241 M) and the levels of chromosomal aberrations (CAs) and single-strand
      breaks (SSBs) in peripheral lymphocytes in a central European population. We also
      measured the irradiation-specific DNA repair rates and the repair rates of 8
      oxoguanines in these individuals. An elevated frequency of CAs was observed in
      individuals with the XPD exon 23 A allele (AA and AC) genotypes (F = 3.6, P =
      0.028, ANOVA). In multifactorial analysis of variance, the XPD exon 23
      polymorphism appeared as a major factor influencing CAs (F = 4.2, P = 0.017).
      SSBs in DNA, on the other hand, were modulated by XPD (F = 4.3, P = 0.023), XPG
      (F = 4.3, P = 0.024) and XRCC1 genotypes (F = 3.0, P = 0.064). Irradiation
      specific DNA repair rates (reflecting mainly base excision repair activity) were
      affected by XRCC1 (F = 5.9, P = 0.010) and XPC polymorphisms (F = 4.2, P = 0.046,
      MANOVA). Our results from this study suggest that markers of genotoxicity are
      associated with polymorphisms in genes encoding DNA repair enzymes.

PMID- 14729592
TI  - The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas
      mediated apoptosis.
AB  - The chemopreventive properties of the isothiocyanates have been attributed to
      their ability to inhibit phase I enzymes that activate procarcinogens, induce
      phase II protective enzymes and trigger apoptosis in transformed cells. In this
      study we provide evidence for a new mechanism of chemoprevention, wherein
      sublethal doses of phenethyl isothiocyanate (PEITC) sensitize cells to Fas
      mediated apoptosis. The phenomenon was observed in the Fas-resistant T24 bladder
      carcinoma cell line and in Jurkat T cells overexpressing the anti-apoptotic
      protein Bcl-2. Caspase-3-like activity was increased up to 20-fold of that
      observed with either PEITC or anti-Fas antibody alone. While PEITC activated ERK,
      JNK and p38, inhibitors of these MAP kinases did not block apoptosis. PEITC
      transiently depleted cellular glutathione, providing a putative mechanism for
      sensitizing the cells to apoptosis. However, lowering glutathione with buthionine
      sulfoximine did not mimic the effect of PEITC. Instead, we propose that PEITC
      promotes apoptosis by directly modifying intracellular thiol proteins. The
      ability of PEITC to sensitize cells to receptor-mediated apoptosis provides an
      additional mechanism to explain its chemopreventive properties.

PMID- 14729593
TI  - Modulation of N-methyl-N-nitrosourea-induced crypt restricted metallothionein
      immunopositivity in mouse colon by a non-genotoxic diet-related chemical.
AB  - Red meat consumption is associated with endogenous metabolic generation of
      mutagenic N-nitroso compounds (NOC) and may be implicated in causation of
      colorectal cancer. Assessment of a biologically relevant dose of NOCs is hampered
      by imperfect understanding of NOC interactions with other dietary components.
      This study tests the hypothesis that NOC effects upon mutational biomarkers in
      mouse colon may be modulated by a non-genotoxic diet-related compound. N-methyl-N
      nitrosourea (MNU) and undegraded lambda carrageenan (lambdaCgN) were selected as
      test chemicals, representing a NOC and a non-genotoxic agent, respectively. Study
      end-points included (i) DNA adduct formation and (ii) metallothionein (MT) crypt
      restricted immunopositivity indices (MTCRII) which are considered representative
      of crypt stem cell mutations. Frequency and size of MT immunopositive foci as
      well as total number of MT immunopositive crypts were assessed. Biologically
      effective doses of MNU and lambdaCgN were determined in model validation studies
      and the agents were then tested alone and in combination. Continuous lambdaCgN
      treatment for 10 weeks induced significantly greater colonic mucosal injury than
      a drinking water control. In combined treatment regimens, lambdaCgN treatment did
      not significantly affect MNU-induced DNA adduct formation. However, combinations
      of lambdaCgN with MNU significantly increased MTCRII in excess of those induced
      by MNU alone. Recurrent or continuous lambdaCgN regimens had greater interactive
      effects with MNU upon MTCRII than short-term lambdaCgN treatment. This study has
      shown that exposure to a non-genotoxic diet-related compound (lambdaCgN)
      modulates the effective NOC dosimetry for induction of MT crypt restricted
      immunopositivity.

PMID- 14729594
TI  - Identification of a genotoxic mechanism for 2-nitroanisole carcinogenicity and of
      its carcinogenic potential for humans.
AB  - 2-Nitroanisole (2-NA) is an important industrial pollutant and a potent bladder
      carcinogen for rodents. The mechanism of its carcinogenicity was investigated in
      this study. Here we have used two independent methods, (32)P-post-labeling and
      (3)H-labeled 2-NA, to show that 2-NA binds covalently to DNA in vitro after
      reductive activation by human hepatic cytosol and xanthine oxidase (XO). We also
      investigated the capacity of 2-NA to form DNA adducts in vivo. Male Wistar rats
      were treated i.p. with 2-NA (0.15 mg/kg body wt daily for 5 days) and DNA from
      several organs was analyzed by (32)P-post-labeling. Two 2-NA-specific DNA
      adducts, identical to those found in DNA incubated with 2-NA and human hepatic
      cytosol or XO in vitro, were detected in the urinary bladder (3.4 adducts/10(7)
      nt), the target organ, and, to a lesser extent, in liver, kidney and spleen. The
      two DNA adducts found in rat tissues in vivo were identified as deoxyguanosine
      adducts derived from a 2-NA reductive metabolite, N-(2
      methoxyphenyl)hydroxylamine. This reactive metabolite of 2-NA was identified in
      incubations with human hepatic cytosol, besides 2-methoxyaniline (o-anisidine).
      The results of our study, the first report on the potential of human cytosolic
      enzymes to contribute to the activation of 2-NA by nitroreduction, strongly
      suggest a carcinogenic potency of this rodent carcinogen for humans.

PMID- 14729595
TI  - Reversal of P-glycoprotein-mediated multidrug resistance by diallyl sulfide in
      K562 leukemic cells and in mouse liver.
AB  - Multidrug resistance (MDR) mediated by the overexpression of drug efflux protein
      P-glycoprotein (P-gp) is one of the major obstacles to successful cancer
      chemotherapy. P-gp acts as an energy-dependent drug efflux pump, reducing the
      intracellular concentration of structurally unrelated drugs. Modulators of P-gp
      function can restore the sensitivity of multidrug-resistant cells to such drugs.
      In the present study, we evaluated the P-gp modulatory potential of diallyl
      sulfide (DAS), a volatile organosulfur compound present in garlic, known to
      possess many medicinal properties, including antimutagenic and anticarcinogenic
      activities. For in vitro studies, K562 leukemic cells were made resistant
      (K562/R) to the cytotoxicity of vinblastine (VBL) by progressive adaptation of
      the sensitive K562 parental cells to VBL. Cross-resistance of K562/R was found
      between vincristine (VCR), doxorubicin and other antineoplastic agents. A non
      toxic concentration of DAS (8.75 x 10(-3) M) enhanced the cytotoxic effects of
      VBL and another vinca alkaloid, VCR, time dependently in VBL-resistant human
      leukemia (K562/R10) cells but had no effect on the parent (K562/S) cells. The
      results show that DAS decreased the induced levels of P-gp in resistant cells
      back to the normal levels as analyzed both qualitatively and quantitatively by
      western blotting and immunocytochemistry. Furthermore, in vivo combination
      studies showed that DAS effectively inhibited vinca alkaloid-induced P-gp
      overexpression in mouse hepatocytes. Quantitation of immunostained tissue
      sections with image analysis showed that the reduction in P-gp levels was up to
      73% for VBL- and 65% for VCR-induced drug resistance. The above features thus
      indicate that DAS can serve as a novel, non-toxic modulator of MDR and can be
      used as a dietary adjuvant.

PMID- 14729596
TI  - Enhancement of development of azoxymethane-induced colonic premalignant lesions
      in C57BL/KsJ-db/db mice.
AB  - Epidemiological studies have shown that obesity and diabetes mellitus may be risk
      factors for colon cancer. However, the underlying mechanisms of how these chronic
      diseases promote colon carcinogenesis remain unknown. C57BL/KsJ-db/db mice have
      obese and diabetic phenotypes because of disruption of the leptin receptor. The
      present study was designed to investigate whether development of azoxymethane
      (AOM)-induced dysplastic and early neoplastic (premalignant) lesions of the colon
      is modulated in db/db mice. Homozygous db/db mice, heterozygous db/+ mice and
      littermate controls (+/+) were injected with AOM under food restriction (
      approximately 10.8 kcal/mouse/day) and killed 5 weeks after the carcinogen
      treatment. Their colons were assessed for premalignant lesions induced by AOM. We
      found a significant increase in the multiplicity of the total premalignant
      lesions in db/db mice when compared with db/+ or +/+ mice. Phenotypically, serum
      leptin and insulin levels in db/db mice were significantly higher than those in
      db/+ or +/+ mice, whereas the body weights and glucose levels in blood of db/db,
      db/+ and +/+ mice were comparable. In addition, immunostaining of the leptin
      receptor and insulin-like growth factor-I receptor showed up-regulation of these
      protein levels specifically in the lesions. Our data indicate that development of
      AOM-induced premalignant lesions is enhanced in db/db mice with hyperleptinemia
      and hyperinsulinemia. The results have important implications for further
      exploration of the possible underlying events that affect the positive
      association between colon cancer and chronic diseases (obesity and diabetes).

PMID- 14729597
TI  - Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic
      effect of Perilla frutescens extract in the murine two-stage skin model.
AB  - Perilla frutescens extract showed marked reduction on tumorigenesis in a murine,
      two-stage skin carcinogenesis model. In this model, cancer is initiated by
      application of 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by application
      of 12-tetradecanoylphorbol 13-acetate (TPA). Following tumor initiation with
      DMBA, topical application of a perilla-derived fraction (PF) at doses of 2
      mg/mouse/application resulted in significant inhibition of tumorigenesis. The
      efficacy of each fraction was correlated with rosmarinic acid (RA) and luteolin
      concentration. Topical application of perilla extract (PE) that contained 68% RA
      or an equivalent amount of commercially available RA showed nearly identical
      antiinflammatory activity 5 h after TPA treatment. Application of luteolin had
      less anti-inflammatory activity. Marked neutrophil infiltration was observed in
      TPA-challenged skin by histological examination using hematoxylin-eosin. This
      change was greatly reduced by pre-treatment with PE or RA. Myeloperoxidase
      activity, a marker of neutrophil recruitment, was also increased in TPA
      challenged skin and was significantly decreased in the PE and RA treated groups.
      Intercellular adhesion molecule 1 and vascular cell adhesion molecule-1 mRNA
      expression levels were reduced by pre-treatment with PE or RA. TPA-induced
      increases in synthesis of the chemokines KC and macrophage inflammatory protein-2
      were significantly decreased by pre-treatment with PE or RA. Prostaglandin E2 and
      leukotriene B4 levels were slightly increased 5 h after TPA treatment. These
      levels were only numerically decreased in the PE and RA treated groups. However,
      induction of cyclooxygenase-2 mRNA expression was obviously reduced by pre
      treatment with PE or RA. Reactive oxygen radical production, detected as
      thiobarbituric acid reactive substance and lipid peroxide, by double treatment of
      TPA was reduced by pre-treatment with PE or RA. Production of 8-hydroxy
      2'deoxyguanosine, which was detected immunohistochemically, was also induced by
      double treatment with TPA. This adduct was barely visible in PE or RA treated
      mice. Thus, we conclude that part of the anticarcinogenic effects of P.frutescens
      extract is due to RA via two independent mechanisms: inhibition of the
      inflammatory response and scavenging of reactive oxygen radicals.

PMID- 14729598
TI  - In vitro characterization of enzymatic properties and inhibition of the p53R2
      subunit of human ribonucleotide reductase.
AB  - p53R2 is a newly identified subunit of ribonucleotide reductase (RR) and plays a
      crucial role in supplying precursors for DNA repair in a p53-dependent manner. In
      our current work, all three human RR subunit proteins (p53R2, hRRM2, and hRRM1)
      were prokaryotically expressed and highly purified. Using an in vitro [(3)H]CDP
      reduction assay, the activity of RR reconstituted with either p53R2 or hRRM2 was
      found to be time, concentration, and hRRM1 dependent. The kinetic activity of
      p53R2-containing RR was about 20-50% lower than that of hRRM2-containing RR.
      Using a synthetic heptapeptide to inhibit RR activity, it was shown that p53R2
      bound to hRRM1 through the same COOH-terminal heptapeptide as hRRM2. However,
      hRRM2 had a 4.76-fold higher binding affinity for hRRM1 than p53R2, which may
      explain the reduced RR activity of p53R2 relative to hRRM2. Of interest, p53R2
      was 158-fold more susceptible to the iron chelator deferoxamine mesylate than
      hRRM2, although the iron content of the two proteins determined by atomic
      absorption spectrometer was almost the same. To the contrary, p53R2 was 2.50-fold
      less sensitive than hRRM2 to the radical scavenger hydroxyurea, whereas EPR
      showed similar spectra of the tyrosyl radical in two proteins. Triapine, a new RR
      inhibitor, was equally potent for p53R2 and hRRM2. These inhibition studies
      showed that the iron center and tyrosyl radical are involved in RR activity for
      both p53R2 and hRRM2. The susceptibility differences to RR inhibitors between
      p53R2 and hRRM2 may lead to a new direction in drug design for human cancer
      treatment.

PMID- 14729599
TI  - Modification of breast cancer risk in young women by a polymorphic sequence in
      the egfr gene.
AB  - The regulation of the epidermal growth factor receptor (egfr) gene in human
      cancer is not yet fully understood. Recent data on a polymorphic CA repeat
      located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA
      simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk
      associated with the egfr gene. Furthermore, we have detected frequent allelic
      imbalances restricted to the egfr CA SSR I in breast cancer tissue and
      nontumorous breast tissue adjacent to invasive and in situ breast cancer
      representing amplifications. Therefore, we conducted a population-based case
      control study to assess the relationship between the egfr polymorphism and breast
      cancer risk. Cases with a first primary breast cancer by age 50 years and age
      matched population controls provided information on known and suspected risk
      factors. The allelic length of the egfr CA SSR was determined in 616 cases and
      1072 population-sampled controls. Genotypes were categorized for analysis by
      allele length. Multivariate logistic regression was used to compare genotype
      distributions, accounting for other risk factors, and to investigate gene
      environment interactions. We found a modifying effect, albeit no main effect, of
      the allelic length of the egfr polymorphism on breast cancer risk. The presence
      of two long alleles (>/==" BORDER="0">19 CA) was associated with a significantly
      elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among
      women with a first-degree family history of breast cancer (P = 0.015 for
      interaction). The risk increase associated with high red meat consumption (OR,
      10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake
      (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two
      long alleles (>/==" BORDER="0">19 CA). The length of the egfr CA SSR may increase
      the risk for familial breast cancers, and its effect could be modulated by
      dietary factors.

PMID- 14729600
TI  - Increased metastatic dissemination in human melanoma xenografts after subcurative
      radiation treatment: radiation-induced increase in fraction of hypoxic cells and
      hypoxia-induced up-regulation of urokinase-type plasminogen activator receptor.
AB  - Cancer patients showing local failure after radiation treatment have increased
      probability for developing metastatic disease. The mechanisms behind this
      observation have not been identified. In the present work, metastatic spread
      after inadequate radiation therapy was studied by using R-18 human melanoma
      xenografts as models of cancer in humans. Pimonidazole was used as a hypoxia
      marker, and hypoxia and urokinase-type plasminogen activator receptor (uPAR)
      expression were detected by immunohistochemistry. R-18 tumors regrowing after
      subcurative irradiation showed a higher frequency of lymph node metastasis than
      unirradiated tumors. The expression of uPAR was up-regulated in hypoxic tumor
      regions, and the fractions of hypoxic and uPAR-positive cells were approximately
      2-fold higher in regrowing irradiated tumors than in untreated tumors. Treatment
      with anti-uPAR antibody blocked metastasis almost completely in irradiated as
      well as unirradiated tumors. The metastatic frequency was higher in tumors
      regrowing after irradiation than in unirradiated tumors because the irradiation
      induced tumor hypoxia, and tumor hypoxia induced up-regulation of uPAR.

PMID- 14729601
TI  - Prostate specific antigen expression is down-regulated by selenium through
      disruption of androgen receptor signaling.
AB  - A previous controlled intervention trial showed that selenium supplementation was
      effective in reducing the incidence of prostate cancer. Physiological
      concentrations of selenium have also been reported to inhibit the growth of human
      prostate cancer cells in vitro. The present study describes the observation that
      selenium was able to significantly down-regulate the expression of prostate
      specific antigen (PSA) transcript and protein within hours in the androgen
      responsive LNCaP cells. Decreases in androgen receptor (AR) transcript and
      protein followed a similar dose and time response pattern upon exposure to
      selenium. The reduction of AR and PSA expression by selenium occurred well before
      any significant change in cell number. With the use of a luciferase reporter
      construct linked to either the PSA promoter or the androgen responsive element,
      it was found that selenium inhibited the trans-activating activity of AR in cells
      transfected with the wild-type AR expression vector. Selenium also suppressed the
      binding of AR to the androgen responsive element site, as evidenced by
      electrophoretic mobility shift assay of the AR-androgen responsive element
      complex. In view of the fact that PSA is a well-accepted prognostic indicator of
      prostate cancer, an important implication of this study is that a selenium
      intervention strategy aimed at toning down the amplitude of androgen signaling
      could be helpful in controlling morbidity of this disease.

PMID- 14729602
TI  - Phosphatidylinositol triphosphate kinase-dependent and c-jun NH2-terminal kinase
      dependent induction of telomerase by calcium requires Pyk2.
AB  - Calcium signaling has been linked to activation of Pyk2, a calcium-dependent,
      focal adhesion kinase-related, non-receptor tyrosine kinase. Signaling via Pyk2
      can activate c-jun NH(2)-terminal kinase (JNK). Calcium has also been shown to
      activate phosphatidylinositol triphosphate kinase and/or JNK. Here, we show that
      calcium signaling in ovarian surface epithelial cells not only induces telomerase
      activity via JNK but also activates Pyk2. Moreover, telomerase activation by Pyk2
      requires JNK activation. In contrast, a kinase-deficient Pyk2 construct failed to
      activate either JNK or telomerase. Finally, we demonstrate that Pyk2 is capable
      of driving the human telomerase reverse transcriptase promoter, resulting in
      telomerase activation. These data suggest a novel role of Pyk2 for telomerase
      regulation.

PMID- 14729603
TI  - Cathepsin B mediates caspase-independent cell death induced by microtubule
      stabilizing agents in non-small cell lung cancer cells.
AB  - We have previously reported that the microtubule stabilizing agents (MSAs)
      paclitaxel, epothilone B and discodermolide induce caspase-independent cell death
      in non-small cell lung cancer (NSCLC) cells. Here we present two lines of
      evidence indicating a central role for the lysosomal protease cathepsin B in
      mediating cell death. First, inhibition of cathepsin B, and not of caspases or
      other proteases, such as cathepsin D or calpains, results in a strong protection
      against drug-induced cell death in several NSCLC cells. Second, MSAs trigger
      disruption of lysosomes and release and activation of cathepsin B. Interestingly,
      inhibition of cathepsin B prevents the appearance of multinucleated cells, an
      early characteristic of MSA-induced cell death, pointing to a central, proximal
      role for cathepsin B in this novel cell death pathway.

PMID- 14729604
TI  - 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human
      osteosarcoma and non-small cell lung cancers in vivo.
AB  - Slow-growing cell populations located within solid tumors are difficult to target
      selectively because most cells in normal tissues also have low replication rates.
      However, a distinguishing feature between slow-growing normal and tumor cells is
      the hypoxic microenvironment of the latter, which makes them extraordinarily
      dependent on anaerobic glycolysis for survival. Previously, we have shown that
      hypoxic tumor cells exhibit increased sensitivity to inhibitors of glycolysis in
      three distinct in vitro models. Based on these results, we predicted that
      combination therapy of a chemotherapeutic agent to target rapidly dividing cells
      and a glycolytic inhibitor to target slow-growing tumor cells would have better
      efficacy than either agent alone. Here, we test this strategy in vivo using the
      glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in combination with Adriamycin
      (ADR) or paclitaxel in nude mouse xenograft models of human osteosarcoma and non
      small cell lung cancer. Nude mice implanted with osteosarcoma cells were divided
      into four groups as follows: (a) untreated controls; (b) mice treated with ADR
      alone; (c) mice treated with 2-DG alone; or (d) mice treated with a combination
      of ADR + 2-DG. Treatment began when tumors were either 50 or 300 mm(3) in volume.
      Starting with small or large tumors, the ADR + 2-DG combination treatment
      resulted in significantly slower tumor growth (and therefore longer survival)
      than the control, 2-DG, or ADR treatments (P < 0.0001). Similar beneficial
      effects of combination treatment were found with 2-DG and paclitaxel in the MV522
      non-small cell lung cancer xenograft model. In summary, the treatment of tumors
      with both the glycolytic inhibitor 2-DG and ADR or paclitaxel results in a
      significant reduction in tumor growth compared with either agent alone. Overall,
      these results, combined with our in vitro data, provide a rationale for
      initiating clinical trials using glycolytic inhibitors in combination with
      chemotherapeutic agents to increase their therapeutic effectiveness.

PMID- 14729605
TI  - Nur77 activated by hypoxia-inducible factor-1alpha overproduces
      proopiomelanocortin in von Hippel-Lindau-mutated renal cell carcinoma.
AB  - Mutation in the von Hippel-Lindau (VHL) protein associated with renal cell
      carcinoma causes hypoxia-inducible factor (HIF) to stabilize and consequently to
      induce various HIF-targeting proteins. In this study, we found that
      proopiomelanocortin (POMC), an adrenocorticotropic hormone precursor, is up
      regulated constitutively in VHL-mutated renal cell carcinoma. A critical
      transcription factor responsible for POMC overproduction was identified as Nur77,
      a member of the orphan steroid receptor superfamily. Little is known about how
      VHL mutation leads to activation of Nur77. We report that Nur77 is directly
      regulated by HIF. We show that HIF-1alpha, but not HIF-2alpha, binds to a
      putative HIF responsive element in the Nur77 promoter, activating the expression
      of Nur77. Mutation or deletion of the HIF binding site in the Nur77 promoter
      abrogates activation of a luciferase reporter gene under the control of Nur77
      promoter by HIF-1alpha. The treatment of Nur77 antisense oligonucleotide reduces
      POMC transcription under hypoxic conditions. We confirmed that Nur77 and POMC are
      up-regulated in VHL-mutated renal cell carcinoma. In this study, we provide the
      first molecular evidence that Nur77 activated by HIF under hypoxic conditions
      regulates production of the peptide hormone precursor POMC.

PMID- 14729606
TI  - Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer
      cell lines.
AB  - Gene amplification is an important mechanism of oncogene activation in breast and
      other cancers. Characterization of amplified regions of the genome in breast
      cancer has led to the identification of important oncogenes including erbB-2/HER
      2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is
      amplified in 10-15% of human breast cancers. The putative oncogene FGFR1
      localizes to this region; however, we show evidence that FGFR inhibition fails to
      slow growth of three breast cancer cell lines with 8p11-p12 amplification. We
      present a detailed analysis of this amplicon in three human breast cancer cell
      lines using comparative genomic hybridization, traditional Southern and Northern
      analysis, and chromosome 8 cDNA microarray expression profiling. This study has
      identified new candidate oncogenes within the 8p11-p12 region, supporting the
      hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast
      cancers with proximal 8p amplification.

PMID- 14729607
TI  - Hepatocarcinogenesis in mice with beta-catenin and Ha-ras gene mutations.
AB  - We have established previously a mouse strain containing a mutant beta-catenin
      allele of which exon 3 was sandwiched by loxP sequences [Catnb(lox(ex3))]. In
      this mouse strain, a Wnt-activating beta-catenin mutation alone is insufficient
      for hepatocarcinogenesis, but additional mutations or epigenetic changes may be
      required. Here we report that hepatocellular carcinoma develops at the 100%
      incidence in mice with simultaneous mutations in the beta-catenin and H-ras genes
      that are introduced by adenovirus-mediated Cre expression. Although H-ras
      mutation alone rapidly causes large cell dysplasia in the hepatocytes, these
      cells show no autonomous growth within 1 week after infection of the Cre
      adenovirus. However, simultaneous induction of an additional mutation in the beta
      catenin gene causes a clonal expansion of such dysplastic cells, followed by
      nodular formation and development of hepatocellular carcinoma. These results
      indicate that beta-catenin mutations play a critical role in hepatocarcinogenesis
      in cooperation with another oncogene and that these mice provide a convenient
      model to investigate early steps of hepatocarcinogenesis.

PMID- 14729608
TI  - Identification of a gene expression signature associated with recurrent disease
      in squamous cell carcinoma of the head and neck.
AB  - Molecular studies of squamous cell carcinoma of the head and neck (HNSCC) have
      demonstrated multiple genetic abnormalities such as activation of various
      oncogenes (Ras, Myc, epidermal growth factor receptor, and cyclin D1), tumor
      suppressor gene inactivation (TP53 and p16), and loss of heterozygosity at
      numerous chromosomal locations. Despite these observations, accurate and reliable
      biomarkers that predict patients at highest risk for local recurrence have yet to
      be defined. In an effort to identify gene expression signatures that may serve as
      biomarkers, we studied 41 squamous cell carcinoma tumors (25 primary and 16
      locally recurrent) from various anatomical sites and 13 normal oral mucosal
      biopsy samples from healthy volunteers with microarray analysis using Affymetrix
      U133A GeneChip arrays. Differentially expressed genes were identified by
      calculating generalized t tests (P < 0.001) and applying a series of filtering
      criteria to yield a highly discriminant list of 2890 genes. Hierarchical
      clustering and image generation using standard software were used to visualize
      gene expression signatures. Several gene expression signatures were readily
      identifiable in the HNSCC tumors, including signatures associated with
      proliferation, extracellular matrix production, cytokine/chemokine expression,
      and immune response. Of particular interest was the association of a gene
      expression signature enriched for genes involved in tumor invasion and metastasis
      with patients experiencing locally recurrent disease. Notably, these tumors also
      demonstrated a marked absence of an immune response signature suggesting that
      modulation of tumor-specific immune responses may play a role in local treatment
      failure. These data provide evidence for a new gene expression-based biomarker of
      local treatment failure in HNSCC.

PMID- 14729609
TI  - Loss of heterozygosity and its correlation with expression profiles in subclasses
      of invasive breast cancers.
AB  - Gene expression array profiles identify subclasses of breast cancers with
      different clinical outcomes and different molecular features. The present study
      attempted to correlate genomic alterations (loss of heterozygosity; LOH) with
      subclasses of breast cancers having distinct gene expression signatures.
      Hierarchical clustering of expression array data from 89 invasive breast cancers
      identified four major expression subclasses. Thirty-four of these cases
      representative of the four subclasses were microdissected and allelotyped using
      genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.).
      LOH was determined by comparing tumor and normal single nucleotide polymorphism
      allelotypes. A newly developed statistical tool was used to determine the
      chromosomal regions of frequent LOH. We found that breast cancers were highly
      heterogeneous, with the proportion of LOH ranging widely from 0.3% to >60% of
      heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q,
      and 14q, sites reported in previous LOH studies. Signature LOH events were
      discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p
      marked a subclass of breast cancers with "basal-like" expression profiles,
      distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a
      subclass of estrogen receptor-positive breast cancers. Finding unique LOH
      patterns in different groups of breast cancer, in part defined by expression
      signatures, adds confidence to newer schemes of molecular classification.
      Furthermore, exclusive association between biological subclasses and restricted
      LOH events provides rationale to search for targeted genes.

PMID- 14729610
TI  - Host gene induction and transcriptional reprogramming in Kaposi's sarcoma
      associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B
      cells: insights into modulation events early during infection.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is etiologically linked to
      the endothelial tumor Kaposi's sarcoma and with two lymphoproliferatve disorders,
      primary effusion lymphoma and multicentric Castleman's disease. HHV-8 infects a
      variety of target cells both in vivo and in vitro, binds to the in vitro target
      cells via cell surface heparan sulfate, and uses the alpha(3)beta(1) integrin as
      one of the entry receptors. Within minutes of infection, HHV-8 induced the
      integrin-mediated signaling pathways and morphological changes in the target
      cells (S. M. Akula et al., Cell, 108: 407-419, 2002; P. P. Naranatt et al., J.
      Virol., 77: 1524-1539, 2003). As an initial step toward understanding the role of
      host genes in HHV-8 infection and pathogenesis, modulation of host cell gene
      expression immediately after infection was examined. To reflect HHV-8's broad
      cellular tropism, mRNAs collected at 2 and 4 h after infection of primary human
      endothelial [human adult dermal microvascular endothelial cells (HMVECd)] and
      foreskin fibroblast [human foreskin fibroblast (HFF)] cells and human B cell line
      (BJAB) were analyzed by oligonucleotide array with approximately 22,000 human
      transcripts. With a criteria of >2-fold gene induction as significant,
      approximately 1.72% of the genes were differentially expressed, of which, 154
      genes were shared by at least two cells and 33 genes shared by all three cells.
      HHV-8-induced transcriptional profiles in the endothelial and fibroblast cells
      were closely similar, with substantial differences in the B cells. In contrast to
      the antiapoptotic regulators induced in HMVECd and HFF cells, proapoptotic
      regulators were induced in the B cells. A robust increase in the expression of
      IFN-induced genes suggestive of innate immune response induction was observed in
      HMVECd and HFF cells, whereas there was a total lack of immunity related protein
      inductions in B cells. These striking cell type-specific behaviors suggest that
      HHV-8-induced host cell gene modulation events in B cells may be different
      compared with the adherent endothelial and fibroblast target cells. Functional
      clustering of modulated genes identified several host molecules hitherto unknown
      to HHV-8 infection. These results indicate that early during infection, HHV-8
      reprograms the host transcriptional machinery regulating a variety of cellular
      processes including apoptosis, transcription, cell cycle regulation, signaling,
      inflammatory response, and angiogenesis, all of which may play important roles in
      the biology and pathogenesis of HHV-8.

PMID- 14729611
TI  - Cyclophilin D, a component of the permeability transition-pore, is an apoptosis
      repressor.
AB  - The permeability transition (PT)-pore is an important proapoptotic protein
      complex in mitochondria. Although it is activated by many signals for apoptosis
      induction, the role of its various subunits in cell death induction has remained
      largely unknown. We found that of its components, only the voltage-dependent
      anion channel in the outer mitochondrial membrane and the adenine nucleotide
      translocator-1 (ANT-1), a PT-pore subunit of the inner membrane, are apoptosis
      inducers. We also report that ANT-1's direct interactor, cyclophilin D, can
      specifically repress ANT-1-induced apoptosis. In addition, cotransfection
      experiments revealed that for a diverse range of apoptosis inducers, cyclophilin
      D shows the same repression profile as the compound bongkrekic acid, a specific
      inhibitor of the PT-pore. This activity seems to be independent of its chaperone
      activity, the only known function of cyclophilin D to date. Importantly,
      cyclophilin D is specifically up-regulated in human tumors of the breast, ovary,
      and uterus, suggesting that inhibition of the PT-pore via up-regulation of
      cyclophilin D plays a role in tumorigenesis.

PMID- 14729612
TI  - Nickel compounds act through phosphatidylinositol-3-kinase/Akt-dependent,
      p70(S6k)-independent pathway to induce hypoxia inducible factor transactivation
      and Cap43 expression in mouse epidermal Cl41 cells.
AB  - Nickel compounds are a somewhat unique class of carcinogens. Previous studies
      have demonstrated that NiCl(2) exposure leads to marked induction of hypoxia
      inducible factor 1 (HIF-1) in human osteosarcoma and BALB/c 3T3 cells, a
      transcription factor that has been considered to play an important role in tumor
      promotion and progression. However, the signal transduction pathways leading to
      HIF-1 induction are not well understood. The present study indicated that
      exposure of mouse epidermal Cl41 cells to either Ni(3)S(2) or NiCl(2) resulted in
      activation of phosphatidylinositol 3-kinase (PI-3K), Akt, and p70 S6 kinase
      (p70(S6k)). Inhibition of PI-3K, Akt, and p70(S6k) by overexpression of a
      dominant-negative mutant of PI-3K (Deltap85) impaired nickel-induced HIF-1
      transactivation. Furthermore, an overexpression of the dominant-negative Akt
      mutant (Akt-T308A/S473A) blocked nickel-induced Akt phosphorylation and HIF-1
      transactivation, whereas inhibition of p70(S6k) activation by pretreatment of
      cells with rapamycin did not show significant inhibitory effects on HIF-1
      transactivation induced by nickel compounds. Consistent with HIF-1
      transactivation, inhibition of the PI-3K/Akt pathway by either overexpression of
      Deltap85 or Akt-T308A/S473A caused dramatic inhibition of Cap43 protein
      expression induced by nickel compounds, whereas pretreatment of cells with
      rapamycin did not exhibit inhibition of Cap43 induction. These results
      demonstrated that nickel compounds induce HIF-1 transactivation and Cap43 protein
      expression through a PI-3K/Akt-dependent and p70(S6k)-independent pathway. This
      study should help us understand the signal transduction pathways involved in the
      carcinogenic effects of nickel compounds.

PMID- 14729613
TI  - Identification of the E1A-regulated transcription factor p120 E4F as an
      interacting partner of the RASSF1A candidate tumor suppressor gene.
AB  - Epigenetic inactivation of the candidate tumor suppressor gene RASSF1A is a
      frequent and critical event in the pathogenesis of many human cancers. The
      RASSF1A protein contains a Ras association domain, suggesting a role in Ras-like
      signaling pathways, and has also been implicated in cell cycle progression.
      However, the preliminary data suggests that the RASSF1A gene product is likely to
      have multiple functions. To identify novel RASSF1A functions, we have sought to
      identify interacting proteins by yeast two-hybrid analysis in a human brain cDNA
      library. We identified the E1A-regulated transcription factor p120(E4F) as a
      RASSF1A interacting partner in yeast and mammalian cells, and demonstrated that
      RASSF1A protein and p120(E4F) form a complex in vivo. The interaction between
      RASSF1A and p120(E4F) was confirmed by both in vitro and in vivo pull downs and
      coimmunoprecipitation assays. In addition, specific inactivation of RASSF1A by
      short interfering RNA disrupts binding of RASSF1A to p120(E4F) in
      coimmunoprecipitation assays. In addition, we demonstrated enhanced G(1) cell
      cycle arrest and S phase inhibition by propidium iodide staining of p120(E4F) in
      the presence of RASSF1A. As p120(E4F) has been reported previously to interact
      with p14ARF, retinoblastoma, and p53, these findings provide an important link
      between the function of RASSF1A and other major human tumor suppressor genes.

PMID- 14729614
TI  - Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive
      oxygen species and inhibition of survival signaling.
AB  - Although arsenic trioxide (As(2)O(3)) induces apoptosis in a relatively wide
      spectrum of tumors, the sensitivity of different cell types to this treatment
      varies to a great extent. Because reactive oxygen species (ROS) are critically
      involved in As(2)O(3)-induced apoptosis, we attempted to explore the possibility
      that elevating the cellular ROS level might be an approach to facilitate
      As(2)O(3)-induced apoptosis. Emodin, a natural anthraquinone derivative, was
      selected because its semiquinone structure is likely to increase the generation
      of intracellular ROS. Its independent and synergistic effects with As(2)O(3) in
      cytotoxicity were studied, and the plausible signaling mechanism was investigated
      in HeLa cells. Cell Proliferation Assay and flow cytometry were used to assess
      cell viability and apoptosis. Electrophoretic mobility shift assay, luciferase
      reporter assay, and Western blotting were performed to analyze signaling
      alteration. The results demonstrated that coadministration of emodin, at low
      doses of 0.5-10 micro M, with As(2)O(3) enhanced As(2)O(3)-rendered cytotoxicity
      on tumor cells, whereas these treatments caused no detectable proproliferative or
      proapoptotic effects on nontumor cells. ROS generation was increased, and
      activation of nuclear factor kappaB and activator protein 1 was suppressed by
      coadministration. All enhancements by emodin could be abolished by the
      antioxidant N-acetyl-L-cysteine. Therefore, we concluded that emodin sensitized
      HeLa cells to As(2)O(3) via generation of ROS and ROS-mediated inhibition on two
      major prosurvival transcription factors, nuclear factor kappaB and activator
      protein 1. This result allows us to propose a novel strategy in chemotherapy that
      uses mild ROS generators to facilitate apoptosis-inducing drugs whose efficacy
      depends on ROS.

PMID- 14729615
TI  - Expression and activation of signal regulatory protein alpha on astrocytomas.
AB  - High-grade astrocytomas and glioblastomas are usually unresectable because they
      extensively invade surrounding brain tissue. Here, we report the expression and
      function of a receptor on many astrocytomas that may alter both the proliferative
      and invasive potential of these tumors. Signal regulatory protein (SIRP) alpha1
      is an immunoglobulin superfamily transmembrane glycoprotein that is normally
      expressed in subsets of myeloid and neuronal cells. Transfection of many cell
      types with SIRPalpha1, including glioblastomas, has been shown to inhibit their
      proliferation in response to a range of growth factors. Furthermore, the
      expression of a murine SIRPalpha1 mutant has been shown to enhance cell adhesion
      and initial cell spreading but to inhibit cell extension and movement. The
      extracellular portion of SIRPalpha1 binds CD47 (integrin-associated protein),
      although this interaction is not required for integrin-mediated activation of
      SIRPalpha1. On phosphorylation, SIRPalpha1 recruits the tyrosine phosphatases SHP
      1 and SHP-2, which are important in its functions. Although SHP-1 is uniquely
      expressed on hematopoietic cells, SHP-2 is ubiquitously expressed, so that
      SIRPalpha1 has the potential to function in many cell types, including
      astrocytomas. Because SIRPalpha1 regulates cell functions that may contribute to
      the malignancy of these tumors, we examined the expression of SIRPs in
      astrocytoma cell lines by flow cytometry using a monoclonal antibody against all
      SIRPs. Screening of nine cell lines revealed clear cell surface expression of
      SIRPs on five cell lines, whereas Northern blotting for SIRPalpha transcripts
      showed mRNA present in eight of nine cell lines. All nine cell lines expressed
      the ligand for SIRPalpha1, CD47. To further examine the expression and function
      of SIRPs, we studied the SF126 and U373MG astrocytoma cell lines, both of which
      express SIRPs, in greater detail. SIRP transcripts in these cells are identical
      in sequence to SIRPalpha1. The expressed deglycosylated protein is the same size
      as SIRPalpha1, but in the astrocytoma cells, it is underglycosylated compared
      with SIRPalpha1 produced in transfected Chinese hamster ovary cells. It is
      nonetheless still capable of binding soluble CD47. Moreover, SIRPalpha1 in each
      of the two cell lines recruited SHP-2 on phosphorylation, and SIRPalpha1
      phosphorylation in cultured cells is CD47 dependent. Finally, examination of
      frozen sections from 10 primary brain tumor biopsies by immunohistochemistry
      revealed expression of SIRPs on seven of the specimens, some of which expressed
      high levels of SIRPs. Most of the tumors also expressed CD47. This is the first
      demonstration that astrocytomas can express SIRPalpha. Given the known role of
      SIRPalpha in regulating cell adhesion and responses to mitogenic growth factors,
      the expression of SIRPalpha1 on astrocytomas may be of considerable importance in
      brain tumor biology, and it offers the potential of a new avenue for therapeutic
      intervention.

PMID- 14729616
TI  - Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell
      survival.
AB  - Metastatic tumor cells originating from cancers of a variety of tissues such as
      breast, skin, and prostate may remain dormant for long periods of time. In the
      case of uveal melanoma, the principal malignancy of the eye, complete removal of
      the primary tumor by enucleation can nonetheless be followed by metastatic tumor
      growth in distant organs months, years, or even decades later. This suggests that
      tumor cells have already spread to secondary sites at the time of treatment and
      remain dormant as micrometastases. Identifying factors that govern long-lived
      survival of metastatic tumor cells is therefore key to decreasing mortality
      associated with this and other diseases. While investigating factors
      differentially expressed in melanoma cells and normal melanocytes, we identified
      the receptor tyrosine kinase Axl and found up-regulation of Axl in uveal
      melanomas and melanoma cell lines by RNase protection, Western analysis, and
      immunohistochemistry. Axl has been shown to mediate cell growth and survival
      through its ligand Gas6 in non-transformed cells. To test whether stimulation of
      Axl can enhance survival of uveal melanoma cells, we assessed the degree of
      mitogenesis and cell survival by bromodeoxyuridine incorporation and trypan blue
      exclusion, respectively, upon stimulation of Mel 290 uveal melanoma cells with
      Gas6 in vitro. We show that Gas6 mediates mitogenesis and cell survival in Mel
      290 cells. We further demonstrate that these effects occur specifically through
      the Axl receptor by modulating the expression of Axl with an antisense construct.
      cDNA microarray analysis of 12,687 genes then revealed that Gas6 stimulation of
      Axl in Mel 290 cells results primarily in the down-regulation of Cyr61, a member
      of the CCN protein family involved in tumor progression. These data show that the
      Axl pathway mediates increased survival of uveal melanoma cells, potentially
      advantageous during cancer dormancy, and that Axl may function in part through
      regulation of Cyr61.

PMID- 14729617
TI  - Alpha7-nicotinic acetylcholine receptors affect growth regulation of human
      mesothelioma cells: role of mitogen-activated protein kinase pathway.
AB  - This study presents data suggesting that both human mesothelioma (cell lines and
      human mesothelioma biopsies) and human normal mesothelial cells express receptors
      for acetylcholine and that stimulation of these receptors by nicotine prompted
      cell growth via activation of nicotinic cholinergic receptors. Thus, these data
      demonstrate that: (a) human mesothelioma cells and human biopsies of mesothelioma
      as well as of normal pleural mesothelial cells express functionally alpha-7
      nicotinic acethlycholine receptors, evaluated by alpha-bungarotoxin-FITC binding,
      receptor binding assay, Western blot, and reverse transcription-PCR; (b) choline
      acetyltransferase immunostaining is present in mesothelioma cells; (c)
      mesothelioma cell growth is modulated by the cholinergic system in which agonists
      (i.e., nicotine) has a proliferative effect, and antagonists (i.e., curare) has
      an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle;
      (d) nicotine induces Ca(+2) influx, evaluated by [(45)Ca(2+)] uptake, and
      consequently activation of mitogen-activated protein kinase pathway
      (extracellular signal-regulated kinase and p90(RSK) phosphorylation), evaluated
      by Western blot; and (e) apoptosis mechanisms in mesothelioma cells are under the
      control of the cholinergic system (nicotine antiapoptotic via induction of
      nuclear factor-kappaB complexes and phosphorylation of Bad at Ser(112); curare
      proapoptotic via G(0)-G(1) arrest p21(waf-1) dependent but p53 independent). The
      involvement of the nonneuronal cholinergic system in mesothelioma appears
      reasonable and open up new therapeutic strategies.

PMID- 14729618
TI  - Inhibition of tumorigenicity and metastasis of human melanoma cells by anti
      cathepsin L single chain variable fragment.
AB  - We demonstrated previously that the switch from nonmetastatic to highly
      metastatic phenotype of human melanoma cells is directly related to secretion of
      procathepsin L form. This cysteine proteinase was identified on the basis of its
      property to cleave human C3, the third component of complement. In an attempt to
      control procathepsin L secretion, we have recently generated an anti-cathepsin L
      single chain variable fragment (ScFv) from an anti-cathepsin L monoclonal
      antibody generated against recombinant cathepsin L. We herein selected clones
      stably transfected with this anti-cathepsin L ScFv and analyzed them for changes
      in tumor growth and metastasis. We show that in stably transfected clones, anti
      cathepsin L ScFv strongly inhibited the secretion of procathepsin L without
      modifying the intracellular amount or processing pattern of cathepsin L forms.
      Confocal analysis demonstrated colocalization of endogenous cathepsin L and anti
      cathepsin L ScFv. In addition, expression of this ScFv strongly inhibited
      generation of tumor and metastasis by these human melanoma clones in nude mice.
      In vivo, the anti-cathepsin L ScFv-transfected cells produced tumors with
      decreased vascularization (angiogenesis) concomitant with increased apoptosis of
      tumor cells. Matrigel assay also demonstrated that melanoma invasiveness was
      completely abolished. Thus, this is the first demonstration that anti-cathepsin L
      ScFv could be used to inhibit the tumorigenic and metastatic phenotype of human
      melanoma, depending on procathepsin L secretion, and could therefore be used as a
      molecular tool in a therapeutic cellular approach.

PMID- 14729619
TI  - Tumor cell-derived nitric oxide is involved in the immune-rejection of an
      immunogenic murine lymphoma.
AB  - The roles played by host-derived nitric oxide (NO) in the growth and subsequent
      immune rejection of a immunogenic murine lymphoma were investigated by growing
      the tumor in mice in which the gene for either inducible NO synthase (iNOS) or
      endothelial NOS (eNOS) had been ablated. This showed that NO from tumor
      infiltrating host cells had no significant effect on either tumor growth or
      immune rejection, although measurements of tumor nitrite levels and protein
      nitration showed that there had been significant NO production in the rejected
      tumors, in both the eNOS and iNOS knockout mice. Inhibition of both tumor and
      host NOS activities, with an iNOS-selective inhibitor (1400W), a nonselective NOS
      inhibitor [Nomega-nitro-L-arginine methyl ester (L-NAME)], or scavenging NO with
      a ruthenium-based scavenger, significantly delayed tumor rejection, while having
      no appreciable effect on tumor growth. Incubation of tumor cells with medium
      taken from cultured splenocytes, that had been isolated from immunized animals
      and activated by incubating them with irradiated tumor cells, resulted in an
      increase in tumor cell NOS activity and an increase in tumor cell apoptosis,
      which could be inhibited using L-NAME. We propose that, during the immune
      rejection of this tumor model, there is induction of tumor NOS activity by
      cytokines secreted by activated lymphocytes within the tumor and that this
      results in increased levels of tumor NO that induce tumor cell apoptosis and
      facilitate immune rejection of the tumor.

PMID- 14729620
TI  - Cell surface-dependent generation of angiostatin4.5.
AB  - Angiostatin4.5 (AS4.5) is a naturally occurring human angiostatin isoform,
      consisting of plasminogen kringles 1-4 plus 85% of kringle 5 (amino acids Lys78
      to Arg529). Prior studies indicate that plasminogen is converted to AS4.5 in a
      two-step reaction. First, plasminogen is activated to plasmin. Then plasmin
      undergoes autoproteolysis within the inner loop of kringle 5, which can be
      induced by a free sulfhydryl donor or an alkaline pH. We now demonstrate that
      plasminogen can be converted to AS4.5 in a cell membrane-dependent reaction.
      Actin was shown previously to be a surface receptor for plasmin(ogen). We now
      show that beta-actin is present on the extracellular membranes of cancer cells
      (PC-3, HT1080, and MDA-MB231), and beta-actin can mediate plasmin binding to the
      cell surface and autoproteolysis to AS4.5. In the presence of beta-actin, no
      small molecule-free sulfhydryl donor is needed for generation of AS4.5.
      Antibodies to actin reduced membrane-dependent generation of AS4.5 by 70%. In a
      cell-free system, addition of actin to in vitro-generated plasmin resulted in
      stoichiometric conversion to AS4.5. Annexin II and alpha-enolase have been
      reported to be plasminogen receptors, but we did not demonstrate a role for these
      proteins in conversion of plasminogen to AS4.5. Our data indicate that membrane
      associated beta-actin, documented previously as a plasminogen receptor, is a key
      cell membrane receptor capable of mediating conversion of plasmin to AS4.5. This
      conversion may serve an important role in regulating tumor angiogenesis,
      invasion, and metastasis, and surface beta-actin may also serve as a prognostic
      marker to predict tumor behavior.

PMID- 14729621
TI  - Angiogenic acceleration of Neu induced mammary tumor progression and metastasis.
AB  - The Neu (ErbB2, HER2) member of the epidermal growth factor receptor family is
      implicated in many human breast cancers. We have tested the importance of
      increased angiogenic signaling in the NeuYD [mouse mammary tumor virus (MMTV)
      Neu(ndl)-YD5] mammary tumor model. Transgenic mice expressing vascular
      endothelial growth factor (VEGF)(164) from the MMTV promoter were generated.
      These mice expressed VEGF(164) RNA and protein at 20- to 40-fold higher levels
      throughout mammary gland development but exhibited normal mammary gland
      development and function. However, in combination with the NeuYD oncogene,
      VEGF(164) expression resulted in increased vascularization of hyperplastic
      mammary epithelium and dramatic acceleration of tumor appearance from 111 to 51
      days. Gene expression profiling also indicated that the VEGF-accelerated tumors
      were substantially more vascularized and less hypoxic. The preferential
      vascularization of early hyperplastic portions of mammary epithelia in NeuYD;MMTV
      VEGF animals was associated with NeuYD RNA expression, disorganization of the
      tight junctions, and overlapping transgenic VEGF expression. NeuYD;MMTV-VEGF(164)
      bigenic, tumor-bearing animals resulted in an average of 10 tumor cell
      colonies/lung lodged within vascular spaces. No similar lung colonies were found
      in control NeuYD mice with similar tumor burdens. Overall, these results
      demonstrate the angiogenic restriction of early hyperplastic mammary lesions.
      They also reinforce in vivo the importance of activated Neu in causing
      disorganization of mammary luminal epithelial cell junctions and provide support
      for an invasion-independent mechanism of metastasis.

PMID- 14729622
TI  - Parathyroid hormone-related protein is an essential growth factor for human clear
      cell renal carcinoma and a target for the von Hippel-Lindau tumor suppressor
      gene.
AB  - Clear cell renal carcinoma (CCRC) is responsible for 2% of cancer-related deaths
      worldwide and is resistant to virtually all therapies, indicating the importance
      of a search for new therapeutic targets. Parathyroid hormone-related protein
      (PTHrP) is a polyprotein derived from normal and malignant cells that regulates
      cell growth. In the current study, we show that blocking PTHrP with antibodies or
      antagonizing the common parathyroid hormone (PTH)/PTHrP receptor, the PTH1
      receptor, dramatically blunts the expansion of human CCRC in vitro by promoting
      cell death. Importantly, in nude mice, anti-PTHrP antibodies induced complete
      regression of 70% of the implanted tumors by inducing cell death. In addition, we
      demonstrate that the von Hippel-Lindau tumor suppressor protein, which functions
      as a gatekeeper for CCRC, negatively regulates PTHrP expression at the post
      transcriptional level. These studies indicate that PTHrP is an essential growth
      factor for CCRC and is a novel target for the von Hippel-Lindau tumor suppressor
      protein. Taken together, these results strongly suggest that targeting the
      PTHrP/PTH1 receptor system may provide a new avenue for the treatment of this
      aggressive cancer in humans.

PMID- 14729623
TI  - Overexpression of the embryonic-lethal abnormal vision-like protein HuR in
      ovarian carcinoma is a prognostic factor and is associated with increased
      cyclooxygenase 2 expression.
AB  - The human embryonic-lethal abnormal vision-like protein HuR is involved in the
      regulation of mRNA turnover and serves as a shuttling protein between the nucleus
      and the cytoplasm that stabilizes mRNAs containing adenine- and uridine-rich
      elements in their 3' untranslated region. We have shown recently that expression
      of cyclooxygenase (COX)-2 is related to poor prognosis in ovarian carcinoma.
      Other studies have shown that the COX-2 mRNA contains an adenine- and uridine
      rich element and is stabilized by HuR. In this study, we investigated the
      expression and cellular distribution of HuR in 83 primary ovarian carcinomas, 16
      borderline tumors of the ovary, 3 normal ovaries, and 9 ovarian carcinoma cell
      lines. Expression of HuR was detected in all cell lines on the mRNA and protein
      level and showed a predominantly nuclear staining in OVCAR-3 cells by confocal
      microscopy. In an immunohistochemical evaluation of human ovarian carcinomas, HuR
      showed a nuclear expression in 81% of tumors. In addition, a cytoplasmic
      expression of HuR was observed in a subgroup of 45% of ovarian carcinomas.
      Nuclear as well as cytoplasmic expression of HuR was significantly increased in
      ovarian carcinomas compared with borderline tumors or normal ovaries. In
      univariate analysis, a significant association between cytoplasmic HuR expression
      and increased COX-2 expression (P = 0.025) as well as between histological grade
      (P = 0.008) and mitotic activity (P = 0.002) was observed, although nuclear
      expression of HuR was not correlated with COX-2 expression or other
      clinicopathological parameters. In Kaplan-Meier survival analysis, increased
      cytoplasmic expression of HuR was a significant prognostic indicator for
      progression-free survival (P = 0.03) as well as overall survival (P = 0.007). In
      multivariate analysis using the Cox regression model, cytoplasmic expression of
      HuR was an independent prognostic parameter for reduced overall survival with a
      relative risk of 2.62 (95% confidence interval, 1.32-5.19). Our results suggest
      that there is a dysregulation of cellular distribution of the mRNA stability
      factor HuR in a subset of invasive ovarian carcinomas. This dysregulation appears
      to result in an increased expression of COX-2, an increased proliferative rate,
      and may lead to a reduced survival time. Additional studies are required to
      analyze the downstream effects of increased cytoplasmic expression of HuR. In
      addition, it would be interesting to investigate the prognostic role of increased
      cytoplasmic expression of HuR in prospective studies.

PMID- 14729624
TI  - Glycine-extended gastrin promotes the growth of lung cancer.
AB  - The less processed forms of gastrin have recently been shown to act as trophic
      factors for both normal and malignant colonic cells. Although incompletely
      processed forms of gastrin such as glycine-extended gastrin and progastrin are
      also expressed in human lung cancers, the clinical significance of this
      expression has not been addressed. Consequently, we investigated the effects of
      overexpression of glycine-extended gastrin in a mouse strain that is prone to
      developing lung cancer and also examined the expression of incompletely processed
      gastrins in primary human lung cancers. We found that transgenic overexpression
      of glycine-extended gastrin in FVB/N mice resulted in a significant increase in
      the prevalence and growth of bronchoalveolar carcinoma. In addition, a
      substantial subset of human lung cancers was found to express progastrin and/or
      glycine-extended gastrin. Overexpression of glycine-extended gastrin by human
      lung cancers was associated with a significantly decreased survival. Taken
      together, these results suggest that glycine-extended gastrin may play a role in
      the growth and progression of some human lung cancers.

PMID- 14729625
TI  - Loss of cables, a cyclin-dependent kinase regulatory protein, is associated with
      the development of endometrial hyperplasia and endometrial cancer.
AB  - Endometrial cancer is the most common gynecological cancer in Western
      industrialized countries. Cables, a cyclin-dependent kinase binding protein,
      plays a role in proliferation and/or differentiation. Cables mutant mice are
      viable, but develop endometrial hyperplasia and carcinoma in situ at a young age.
      Exposure to chronic low levels of estrogen results in development of endometrial
      cancer, similar to that observed in the postmenopausal female. In vitro and in
      vivo studies demonstrate that levels of Cables mRNA in benign human endometrial
      epithelium are up-regulated by progesterone and down-regulated by estrogen.
      Furthermore, nuclear immunostaining for Cables is lost in a high percentage of
      cases of human endometrial hyperplasia and adenocarcinoma, which are likely the
      product of unopposed estrogen. The loss of Cables immunostaining in the human
      endometrial cancer samples correlates with a marked decrease in Cables mRNA.
      Ectopic expression of Cables in human endometrial cells dramatically slows cell
      proliferation. Collectively, these data provide evidence that Cables is
      hormonally regulated and is involved in regulating endometrial cell
      proliferation. In addition, loss or suppression of Cables may be an early step in
      the development of endometrial cancer.

PMID- 14729626
TI  - Mammary tumor induction in transgenic mice expressing an RNA-binding protein.
AB  - We have analyzed mammary tumors arising in transgenic mice expressing a novel,
      multifunctional RNA-binding protein. The protein, which we call the c-myc mRNA
      coding region instability determinant binding protein (CRD-BP), binds to c-myc,
      insulin-like growth factor II, and beta-actin mRNAs, and to H19 RNA. Depending on
      the RNA substrate, the CRD-BP affects RNA localization, translation, or
      stability. CRD-BP levels are high during fetal development but low or
      undetectable in normal adult tissues. The CRD-BP is linked to tumorigenesis,
      because its expression is reactivated in some adult human breast, colon, and lung
      tumors. These data suggest the CRD-BP is a proto-oncogene. To test this idea, the
      CRD-BP was expressed from the whey acidic protein (WAP) promoter in mammary
      epithelial cells of adult transgenic mice. The incidence of mammary tumors was
      95% and 60% in two lines of WAP-CRD-BP mice with high and low relative CRD-BP
      expression, respectively. Some of the tumors metastasized. Nontransgenic mice did
      not develop mammary tumors. H19 RNA and insulin-like growth factor II mRNA were
      up-regulated significantly in non-neoplastic WAP-CRD-BP mammary tissue. WAP-CRD
      BP mice are a novel model for mammary neoplasia and might provide insights into
      human breast cancer biology.

PMID- 14729627
TI  - HER-2/neu-mediated regulation of components of the MHC class I antigen-processing
      pathway.
AB  - Because of its amplification and/or overexpression in many human tumors, the HER
      2/neu proto-oncogene represents an attractive target for T-cell-mediated
      vaccination strategies. However, overexpression of oncogenes is often associated
      with defective expression of components of the MHC class I antigen-processing
      machinery (APM), thereby resulting in an immune escape phenotype of oncogene
      transformed cells. To determine whether HER-2/neu influences the MHC class I
      antigen-processing pathway, the expression pattern of different APM components
      was examined in murine in vitro models of constitutive and tetracycline
      controlled HER-2/neu expression. In comparison with HER-2/neu(-) control cells,
      HER-2/neu(+) fibroblasts exhibit reduced levels of MHC class I surface antigens
      that were associated with impaired expression and/or function of the peptide
      transporter associated with antigen processing, the proteasome subunits low
      molecular weight protein 2 and low molecular weight protein 10, the proteasome
      activators PA28alpha and PA28beta, and tapasin. These APM abnormalities resulted
      in reduced sensitivity to lysis by CTLs. The HER-2/neu-mediated immune escape
      phenotype could be corrected by IFN-gamma treatment. The clinical relevance of
      this finding was supported by an inverse correlation between HER-2/neu and the
      peptide transporter associated with antigen-processing protein expression as
      determined by immunhistochemical analysis of a series of HER-2/neu(-) and HER
      2/neu(+) breast cancer specimens. Thus, a functional link between deficient APM
      component expression and HER-2/neu overexpression is proposed that might
      influence the design of HER-2/neu-targeted T-cell-based immunotherapeutic
      strategies.

PMID- 14729628
TI  - p53 activation in chronic radiation-treated breast cancer cells: regulation of
      MDM2/p14ARF.
AB  - Mammalian cells chronically exposed to ionizing radiation (IR) induce stress
      response with a tolerance to the subsequent cytotoxicity of IR. Although p53 is
      well documented in IR response, the signaling network causing p53 activation in
      chronic IR remains to be identified. Using breast carcinoma MCF+FIR cells that
      showed a transient radioresistance after exposure chronically to fractionated IR
      (FIR), the present study shows that the basal DNA binding and transcriptional
      activity of p53 was elevated by FIR. p53-controlled luciferase activity was
      strikingly induced ( approximately 7.9-fold) with little enhancement of p53/DNA
      binding activity ( approximately 1.3-fold). The phosphorylated p53 (Thr 55) was
      increased in the cytoplasm and nucleus of MCF+FIR but not in the sham-FIR control
      cells. On the contrary, the sham-FIR control MCF-7 cells showed a low p53
      luciferase transcription ( approximately 3-fold) but a striking enhancement of
      p53/DNA binding (12-fold) after 5 Gy of IR. To determine the signaling elements
      regulating p53 activity, DNA microarray of MCF+FIR using sham-FIR MCF-7 cells as
      a reference demonstrated that the mRNA of p21, MDM2, and p14ARF was up-regulated.
      Time course Western blot analysis, however, showed no difference in p21
      induction. In contrast, MDM2 that was absent in control cells and was
      predominantly induced by IR was not induced in MCF+FIR cells. In agreement with
      MDM2 inhibition, MDM2-inhibitory protein p14ARF was increased in MCF+FIR cells.
      In summary, these results demonstrate that up-regulation of p14ARF paralleled
      with MDM2 inhibition contributes to p53 accumulation in the nucleus and causes a
      high responsiveness of p53 in chronic IR-treated breast cancer cells.

PMID- 14729629
TI  - Roles of phosphatidylinositol 3'-kinase and mammalian target of rapamycin/p70
      ribosomal protein S6 kinase in K-Ras-mediated transformation of intestinal
      epithelial cells.
AB  - Phosphatidylinositol 3'-kinase (PI3K) activity is required for Ras- mediated
      transformation of intestinal epithelial cells (IECs). The mammalian target of
      rapamycin (mTOR) and its downstream pathways control the translation of specific
      mRNAs that are required for cell proliferation and transformation. Here, we
      elucidated the roles of PI3K and mTOR in K-Ras-mediated transformation of IECs
      (IEC-6). Induction of K-Ras activated PI3K and mTOR in IECs. p70 ribosomal
      protein S6 kinase activity was induced by K-Ras in a PI3K- and mTOR-dependent
      manner. K-Ras did not significantly alter the phosphorylation of eukaryotic
      initiation factor 4E-binding protein 1. Treatment with either LY-294002 or
      rapamycin inhibited IEC proliferation and resulted in G(1) growth arrest.
      However, it was noted that inhibition of mTOR enhanced K-Ras-mediated
      morphological transformation and increased invasiveness of IECs in a mitogen
      activated protein/extracellular signal-regulated kinase-dependent manner.
      Furthermore, inhibition of PI3K or mTOR impaired the growth of an array of colon
      cancer cells. Spindle transformation, reduced E-cadherin, and increased
      invasiveness were observed in LY-294002-treated Moser cells. Thus, our results
      suggest that K-Ras-mediated transformation of IECs involves activation of the
      PI3K/mTOR pathway. Inhibition of PI3K/mTOR activity leads to G(1) growth arrest
      of transformed IECs. On the other hand, inhibition of PI3K or mTOR may induce the
      epithelial to mesenchymal transdifferentiation of IECs under certain
      circumstances.

PMID- 14729630
TI  - Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and
      malignant cell growth.
AB  - The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in
      transformation, growth, and survival of malignant cells, and has emerged as a
      general and promising target for cancer treatment. However, no fully selective
      IGF-1R inhibitors have thus far been found. This is explained by the fact that
      IGF-1R is highly homologous to the insulin receptor, coinhibition of which may
      cause diabetic response. The receptors are both tyrosine kinases, and their ATP
      binding sites are identical, implying that ATP inhibitors cannot discriminate
      between them. Therefore, the current strategy has been to identify compounds
      interfering with receptor autophosphorylation at the substrate level. In this
      study we investigated the effects of cyclolignans and related molecules on IGF-1R
      activity. We report that certain cyclolignans are potent and selective inhibitors
      of tyrosine phosphorylation of the IGF-1R. Of particular interest was
      picropodophyllin (PPP), which is almost nontoxic (LD(50) >500 mg/kg in rodents).
      PPP efficiently blocked IGF-1R activity, reduced pAkt and phosphorylated
      extracellular signal regulated kinase 1 and 2 (pErk1/2), induced apoptosis in
      cultured IGF-1R-positive tumor cells, and caused complete tumor regression in
      xenografted and allografted mice. PPP did not affect the insulin receptor or
      compete with ATP in an in vitro kinase assay, suggesting that it may inhibit IGF
      1R autophosphorylation at the substrate level. This is also in agreement with our
      molecular model of how the cyclolignans may act on the IGF-1R kinase. Our results
      open the possibility to use PPP or related compounds with inhibitory effects on
      IGF-1R as lead compounds in development of anticancer agents.

PMID- 14729631
TI  - Significant differences in the effects of magnetic field exposure on 7,12
      dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of
      Sprague-Dawley rats.
AB  - We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633,
      1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux
      densities enhance mammary gland tumor development and growth in the 7,12
      dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley
      (SD) rats. We also demonstrated that MF exposure results in an enhanced
      proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al.,
      Cancer Res., 62: 1356-1363, 2002), which is a likely explanation for the
      cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model.
      However, in contrast with our data, in a similar study conducted by Battelle in
      the United States, no evidence for a cocarcinogenic or tumor-promoting effect of
      MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al.,
      Carcinogenesis, 20: 1615-1620, 1999). Probably the most important difference
      between our and the Battelle studies was the use of different substrains of SD
      rats; the United States rats were much more susceptible to DMBA than the rats
      used in our studies. This prompted us to compare different substrains of SD
      outbred rats in our laboratory in respect to MF effects on cell proliferation in
      the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects
      on mammary tumor development and growth in the DMBA model. The SD substrain
      (termed "SD1") used in all of our previous studies was considered MF-sensitive
      and used for comparison with another substrain ("SD2") obtained from the same
      breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined
      after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor
      development and growth in SD1 but not SD2 rats. These data indicate that the
      genetic background plays a pivotal role in effects of MF exposure. Different
      strains or substrains of rats may serve to evaluate the genetic factors
      underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF
      exposure.

PMID- 14729632
TI  - Antitumor efficacy of intermittent treatment schedules with the rapamycin
      derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6
      kinase 1 in peripheral blood mononuclear cells.
AB  - The orally bioavailable rapamycin derivative RAD001 (everolimus) targets the
      mammalian target of rapamycin pathway and possesses potent immunosuppressive and
      anticancer activities. Here, the antitumor activity of RAD001 was evaluated in
      the CA20948 syngeneic rat pancreatic tumor model. RAD001 demonstrated dose
      dependent antitumor activity with daily and weekly administration schedules;
      statistically significant antitumor effects were observed with 2.5 and 0.5 mg/kg
      RAD001 administered daily [treated tumor versus control tumor size (T/C), 23% and
      23-30%, respectively], with 3-5 mg/kg RAD001 administered once weekly (T/C, 14
      36%), or with 5 mg/kg RAD001 administered twice weekly (T/C, 36%). These
      schedules were well tolerated and exhibited antitumor potency similar to that of
      the cytotoxic agent 5-fluorouracil (T/C, 23%). Moreover, the efficacy of
      intermittent treatment schedules suggests a therapeutic window allowing
      differentiation of antitumor activity from the immunosuppressive properties of
      this agent. Detailed biochemical profiling of mammalian target of rapamycin
      signaling in tumors, skin, and peripheral blood mononuclear cells (PBMCs), after
      a single administration of 5 mg/kg RAD001, indicated that RAD001 treatment
      blocked phosphorylation of the translational repressor eukaryotic initiation
      factor 4E-binding protein 1 and inactivated the translational activator ribosomal
      protein S6 kinase 1 (S6K1). The efficacy of intermittent treatment schedules was
      associated with prolonged inactivation of S6K1 in tumors and surrogate tissues (>
      or =72 h). Furthermore, detailed analysis of the dose dependency of weekly
      treatment schedules demonstrated a correlation between antitumor efficacy and
      prolonged effects (> or =7 days) on PBMC-derived S6K1 activity. Analysis of human
      PBMCs revealed that S6K1 also underwent a concentration-dependent inactivation
      after RAD001 treatment ex vivo (>95% inactivation with 20 nM RAD001). In
      contrast, human PBMC-derived eukaryotic initiation factor 4E-binding protein 1
      was present predominantly in the hypophosphorylated form and was unaffected by
      RAD001 treatment. Taken together, these results demonstrate a correlation between
      the antitumor efficacy of intermittent RAD001 treatment schedules and prolonged
      S6K1 inactivation in PBMCs and suggest that long-term monitoring of PBMC-derived
      S6K1 activity levels could be used for assessing RAD001 treatment schedules in
      cancer patients.

PMID- 14729633
TI  - The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits
      retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates
      the mitogen-activated protein kinase pathway.
AB  - Deregulation of the cell cycle commonly occurs during tumorigenesis, resulting in
      unrestricted cell proliferation and independence from mitogens. Cyclin-dependent
      kinase inhibitors have the potential to induce cell cycle arrest and apoptosis in
      cancer cells. CYC202 (R-roscovitine) is a potent inhibitor of CDK2/cyclin E that
      is undergoing clinical trials. Drugs selected to act on a particular molecular
      target may exert additional or alternative effects in intact cells. We therefore
      studied the molecular pharmacology of CYC202 in human colon cancer cells.
      Treatment of HT29 and KM12 colon carcinoma cell lines with CYC202 decreased both
      retinoblastoma protein phosphorylation and total retinoblastoma protein. In
      addition, an increase in the phosphorylation of extracellular signal-regulated
      kinases 1/2 was observed. As a result, downstream activation of the mitogen
      activated protein kinase pathway occurred, as demonstrated by an increase in ELK
      1 phosphorylation and in c-FOS expression. Use of mitogen-activated protein
      kinase kinases 1/2 inhibitors showed that the CYC202-induced extracellular signal
      regulated kinases 1/2 phosphorylation was mitogen-activated protein kinase
      kinases 1/2 dependent but did not contribute to the cell cycle effects of the
      drug, which included a reduction of cells in G(1), inhibition of
      bromodeoxyuridine incorporation during S-phase, and a moderate increase in G(2)-M
      phase. Despite activation of the mitogen-activated protein kinase pathway, cyclin
      D1 protein levels were decreased by CYC202, an effect that occurred
      simultaneously with loss of retinoblastoma protein phosphorylation and inhibition
      of cell cycle progression. The reduced expression of cyclin D1 protein was
      independent of the p38(SAPK) and phosphatidylinositol 3-kinase pathways, which
      are known regulators of cyclin D1 protein. Interestingly, CYC202 caused a clear
      reduction in cyclins D1, A, and B1 mRNA, whereas c-FOS mRNA increased by 2-fold.
      This was accompanied by a loss of RNA polymerase II phosphorylation and total RNA
      polymerase II protein, suggesting that CYC202 was inhibiting transcription,
      possibly via inhibition of CDK7 and CDK9 complexes. It can be concluded that
      although CYC202 can act as a CDK2 inhibitor, it also has the potential to inhibit
      CDK4 and CDK1 activities in cancer cells through the down-regulation of the
      corresponding cyclin partners. This provides a possible mechanism by which CYC202
      can cause a reduction in retinoblastoma protein phosphorylation at multiple sites
      and cell cycle arrest in G(1), S, and G(2)-M phases. In addition to providing
      useful insights into the molecular pharmacology of CYC202 in human cancer cells,
      the results also suggest potential pharmacodynamic end points for use in clinical
      trials with the drug.

PMID- 14729634
TI  - In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas.
AB  - In vivo imaging of endogenously expressed mammalian proteases has been useful for
      the detection of cancer and preneoplastic lesions, for staging of inflammatory
      and autoimmune diseases, and for testing the efficacy of novel protease
      inhibitors. Here we report on the synthesis of a novel imaging probe that is
      specific for HIV-1 protease (PR). The probe was designed to be biocompatible,
      i.v. injectable, and detectable by fluorescence imaging. Human Gli36 glioblastoma
      cells infected with an human simplex virus amplicon vector expressing HIV-1PR
      showed specific fluorescence activation, an effect that could be inhibited by the
      HIV-1PR inhibitor, indinavir. The transfer of the HIV-1PR marker gene could be
      detected in vivo after intratumoral delivery of the human simplex virus-amplicon
      vector. These results are the first proof of principle that viral proteases can
      directly be imaged in vivo. These findings may be directly applicable in using
      viral protease expression as a transgene marker in tumor therapy and may have
      implications in testing the efficacy of HIV-1PR inhibitors in vivo.

PMID- 14729635
TI  - Synergy between celecoxib and radiotherapy results from inhibition of
      cyclooxygenase-2-derived prostaglandin E2, a survival factor for tumor and
      associated vasculature.
AB  - Previous work has demonstrated that selective cyclooxygenase-2 (COX-2) inhibitors
      can act synergistically with radiotherapy to improve tumor debulking and control
      in preclinical models. The underlying mechanism of this remarkable activity has
      not yet been determined. Here, we report that radiation can elevate intratumoral
      levels of COX-2 protein and its products, particularly prostaglandin E(2)
      (PGE(2)). Furthermore, inhibition of COX-2 activity or neutralization of PGE(2)
      activity enhances radiotherapy even in tumors where COX-2 expression is
      restricted to the tumor neovasculature. Direct assessment of vascular function by
      direct contrast enhancement-magnetic resonance imaging showed that the
      combination of radiation and celecoxib lead to enhanced vascular permeability.
      These observations suggest that an important mechanism of celecoxib-induced
      radiosensitization involves inhibition of COX-2-derived PGE(2), thus removing a
      survival factor for the tumor and its vasculature.

PMID- 14729637
TI  - Use of replication-conditional adenovirus as a helper system to enhance delivery
      of P450 prodrug-activation genes for cancer therapy.
AB  - Cytochrome P450 (CYP) gene transfer sensitizes tumor xenografts to anticancer
      prodrugs such as cyclophosphamide (CPA) without a detectable increase in host
      toxicity. Optimal prodrug activation is achieved when a suitable P450 gene (e.g.,
      human CYP2B6) is delivered in combination with NADPH-cytochrome P450 reductase
      (P450R), which encodes the flavoenzyme P450 reductase. We sought to improve this
      gene therapy by coordinated delivery and expression of P450 and P450R on a single
      bicistronic vector using an internal ribosomal entry site (IRES) sequence.
      Retrovirus encoding a CYP2B6-IRES-P450R expression cassette was shown to induce
      strong P450-dependent CPA cytotoxicity in a population of infected 9L gliosarcoma
      cells. Adeno-P450, a replication-defective, E1/E3 region-deleted adenovirus
      engineered to express CYP2B6-IRES-P450R, induced intracellular CPA 4
      hydroxylation, and CPA cytotoxicity, in a broad range of human cancer cell lines.
      However, limited Adeno-P450 gene transfer and CPA chemosensitization was seen
      with certain human tumor cells, notably PC-3 prostate and HT-29 colon cancer
      cells. Remarkable improvements could be obtained by coinfecting the tumor cells
      with Adeno-P450 in combination with Onyx-017, an E1b-55k gene-deleted adenovirus
      that selectively replicates in p53 pathway-deficient cells. Substantial increases
      in gene expression were observed during the early stages of viral infection,
      reflecting an apparent coamplification of the Adeno-P450 genome, followed by
      enhanced viral spread at later stages, as demonstrated in cultured tumor cells,
      and in A549 and PC-3 solid tumor xenografts grown in scid mice. This combination
      of the replication-defective Adeno-P450 with a replication-conditional and tumor
      cell-targeted helper adenovirus dramatically improved the low gene transfer
      observed with some human tumor cell lines and correspondingly increased tumor
      cell-catalyzed CPA 4-hydroxylation, CPA cytotoxicity, and in vivo antitumor
      activity in a PC-3 tumor xenograft model. The use of tumor-selective, replicating
      adenovirus to promote the spread of replication-defective gene therapy vectors,
      such as Adeno-P450, substantially increases the therapeutic potential of
      adenoviral delivery systems, and should lead to increased activity and enhanced
      tumor selectivity of cytochrome P450 and other gene-directed enzyme prodrug
      therapies.

PMID- 14729636
TI  - Expression of the insulin-like growth factor I receptor and urokinase plasminogen
      activator in breast cancer is associated with poor survival: potential for
      intervention with 17-allylamino geldanamycin.
AB  - Urokinase plasminogen activator (uPA) expression in breast cancer is associated
      with relapse and a reduction in disease-specific survival. Thus, efforts are
      under way to identify uPA inhibitors. By screening a chemical library of >1000
      compounds, 17-allyaminogeldanamycin (17AAG) was identified as a potent inhibitor
      of uPA by the National Cancer Institute and is now in Phase I clinical trials. At
      this time, it remains unclear how 17AAG blocks uPA; one possibility is through
      disruption of the insulin-like growth factor I receptor (IGF-IR) pathway. This
      would be consistent with studies from our laboratory showing that activation of
      IGF-IR results in the induction of uPA protein. In the study described herein, we
      observed that IGF-IR and uPA were highly expressed in 87 and 55% of breast cancer
      by screening tumor tissue microarrays representing 930 cases. A significant
      proportion (52.1% = 354 of 680 cases, P < 0.0001) of the patients had tumors
      expressing both proteins. uPA alone (P = 0.033) or in combination with IGF-IR (P
      = 0.0104) was indicative of decreased disease-specific survival. Next, we
      demonstrated that treating MDA-MB-231 cells with increasing concentrations of
      17AAG resulted in IGF-IR degradation (IC(50) = 1.0 micro M) and blocked signal
      transduction through the Akt and mitogen-activated protein kinase pathways.
      Finally, we found that 17AAG had a robust inhibitory effect on the production of
      uPA mRNAand protein in the presence of IGF-I. Thus, our study raises the
      possibility that 17AAG could prove to be an effective therapeutic agent for a
      large number of breast cancer patients by inhibiting the IGF-IR and ultimately
      uPA.

PMID- 14729638
TI  - Inhibition of cytokine-induced microvascular arrest of tumor cells by recombinant
      endostatin prevents experimental hepatic melanoma metastasis.
AB  - We investigated effects of endostatin (ES) in the prometastatic microenvironment
      of inflammation occurring during the microvascular phase of cancer cell
      infiltration in the liver. We used a model of intrasplenic injection of B16
      melanoma (B16M) cells leading to hepatic metastasis through vascular cell
      adhesion molecule-(VCAM-1)-mediated capillary arrest of cancer cells via
      interleukin-18 (IL-18)-dependent mechanism. We show that administration of 50
      mg/kg recombinant human (rh) ES 30 min before B16M, plus repetition of same dose
      for 3 additional days decreased metastasis number by 60%. A single dose of rhES
      before B16M injection reduced hepatic microvascular retention of luciferase
      transfected B16M by 40% and inhibited hepatic production of tumor necrosis factor
      alpha (TNF-alpha) and IL-18 and VCAM-1 expression by hepatic sinusoidal
      endothelia (HSE). Consistent with these data, rhES inhibited VCAM-1-dependent
      B16M cell adhesion to primary cultured HSE receiving B16M conditioned medium, and
      it abolished the HSE cell production of TNF-alpha and IL-18 induced by tumor
      derived vascular endothelial cell growth factor (VEGF). rhES abrogated
      recombinant murine VEGF-induced tyrosine phosphorylation of KDR/flk-1 receptor in
      HSE cells, preventing the proinflammatory action of tumor-derived VEGF on HSE.
      rhES also abolished hepatic production of TNF-alpha, microvascular retention of
      luciferase-transfected B16M, and adhesion of B16M cells to isolated HSE cells,
      all of them induced in mice given 5 micro g/kg recombinant murine VEGF for 18 h.
      This capillary inflammation-deactivating capability constitutes a
      nonantiangiogenic antitumoral action of endostatin that decreases cancer cell
      arrest within liver microvasculature and prevents metastases promoted by
      proinflammatory cytokines induced by VEGF.

PMID- 14729639
TI  - Effects of dexamethasone or celecoxib on biliary toxicity after hepatic arterial
      infusion of 5-fluorodeoxyuridine in a canine model.
AB  - Previous work has shown that in humans the dose-limiting toxicity for
      fluorodeoxyuridine [2-fluoro-5'-deoxyuridine (FdUrd)] when administered by
      hepatic arterial infusion is biliary sclerosis. The current study was undertaken
      to attempt to modify this toxicity in a canine model that has been demonstrated
      to closely mimic the clinical situation. Unlike previous studies using this
      model, in which animals were sacrificed after extensive fibrosis had already
      occurred, the current experiments were designed so that observations of pathology
      were made at an earlier time, when the initial inflammatory injury underlying the
      fibrotic process was still taking place. Implantable pumps were used to deliver
      FdUrd into the hepatic artery of animals at a rate of 0.3 mg/kg/day in the
      presence or absence of 10 mg/week dexamethasone or 100 mg/day of celecoxib for 35
      days, at which time the animals were beginning to show signs of toxicity. After
      evaluation for radiological evidence of biliary obstruction, the animals were
      sacrificed and portions of their livers were processed for examination of
      microscopic pathology and 2-bromo-5'deoxyuridine labeling index. Dexamethasone
      treatment protected the animals from biliary sclerosis determined radiologically,
      further validating this model as being representative of the response in humans.
      Similarly the Cox-2 inhibitor, celecoxib, appeared to provide protection against
      radiological changes of biliary stricture, although possibly to a lesser degree
      than the resultant from dexamethasone. In addition, FdUrd treatment caused
      elevation of the DNA 2-bromo-5'deoxyuridine labeling index above control levels
      in biliary epithelial cells. Dexamethasone and celecoxib each significantly
      attenuated the FdUrd-induced elevation of DNA labeling index in biliary
      epithelium. These findings demonstrate the usefulness of this canine model for
      studying the mechanisms of drug-induced biliary sclerosis and reinforce the
      hypothesis that blocking inflammation may retard the progression of injury that
      eventually leads to fibrosis. This study suggests that clinical testing of
      celecoxib as a preventive for hepatic arterial-FdUrd induced biliary damage could
      prove valuable.

PMID- 14729640
TI  - Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci
      expression by the histone deacetylase inhibitor MS-275.
AB  - Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation for
      cancer therapy. Because HDAC modulates chromatin structure and gene expression,
      parameters considered to influence radioresponse, we have investigated the
      effects of the HDAC inhibitor MS-275 on the radiosensitivity of two human tumor
      cell lines (DU145 prostate carcinoma and U251 glioma). Acetylation status of
      histones H3 and H4 was determined as a function of time after MS-275 addition to
      and removal from culture medium. Histone acetylation increased by 6 h after MS
      275 addition, reaching a maximum between 24 and 48 h of exposure; providing fresh
      drug-free medium then resulted in a decrease in histone acetylation that began by
      6 h and approached untreated levels by 16 h. Treatment of cells with MS-275 for
      48 h followed by irradiation had little or no effect on radiation-induced cell
      death. However, exposure to MS-275 before and after irradiation resulted in an
      increase in radiosensitivity with dose enhancement factors of 1.9 and 1.3 for
      DU145 and U251 cells, respectively. This MS-275 treatment protocol did not result
      in a redistribution of the cells into a more radiosensitive phase of the cell
      cycle or in an increase in apoptosis. However, MS-275 did modify the time course
      of gammaH2AX expression in irradiated cells. Whereas there was no significant
      difference in radiation-induced gammaH2AX foci at 6 h, the number of cells
      expressing gammaH2AX foci was significantly greater in the MS-275-treated cells
      at 24 h after irradiation. These results indicate that MS-275 can enhance
      radiosensitivity and suggest that this effect may involve an inhibition of DNA
      repair.

PMID- 14729641
TI  - Multidrug-resistant cancer cells facilitate E1-independent adenoviral
      replication: impact for cancer gene therapy.
AB  - Resistance to chemotherapy is responsible for a failure of current treatment
      regimens in cancer patients. We have reported previously that the Y-box protein
      YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major
      role in the development of a multidrug resistant-tumor phenotype. YB-1 predicts
      drug resistance and patient outcome in breast cancer. Thus, YB-1 is a promising
      target for new therapeutic approaches to defeat multidrug resistance. In drug
      resistant cancer cells and in adenovirus-infected cells YB-1 is found in the
      nucleus. Nuclear accumulation of YB-1 in adenovirus-infected cells is a function
      of the E1 region, and we have shown that YB-1 facilitates adenovirus replication.
      Here we report that E1A-deleted or mutant adenovirus vectors, such as Ad312 and
      Ad520, replicate efficiently in multidrug-resistant (MDR) cancer cells and induce
      an adenovirus cytopathic effect resulting in host cell lysis. Thus, replication
      defective adenoviruses are a previously unrecognized vector system for a
      selective elimination of MDR cancer cells. Our work forms the basis for the
      development of novel oncolytic adenovirus vectors for the treatment of MDR
      malignant diseases in the clinical setting.

PMID- 14729642
TI  - F16, a mitochondriotoxic compound, triggers apoptosis or necrosis depending on
      the genetic background of the target carcinoma cell.
AB  - Mutations that lead to the emergence of resistance to apoptosis are commonly
      observed among tumor cells. Some of the proteins affected are integral parts of
      the apoptotic cascade such as pro- and antiapoptotic members of the Bcl-2 family.
      F16 is a small molecule that accumulates in mitochondria of a variety of tumor
      cells and interferes with their physiological function. Because this interference
      ultimately triggers apoptosis in many affected cell lines, we examined the effect
      of antiapoptotic Bcl-2 overexpression on the response of cells to F16. Our
      results showed that high levels of Bcl-2 did not block the ability of F16 to
      induce cell death. However, unlike the apoptotic response that followed F16
      treatment of cells with moderate Bcl-2 levels, cells resistant to a variety of
      apoptotic stimuli by virtue of Bcl-2 overexpression succumbed to F16 by necrosis.
      Thus, this dual ability of the mitochondriotoxic compound F16 to induce apoptosis
      and necrosis may represent an added advantage by expanding its spectrum of action
      toward genetically altered tumor cells incapable of apoptosis.

PMID- 14729643
TI  - Sensitization for tumor necrosis factor-related apoptosis-inducing ligand-induced
      apoptosis by the chemopreventive agent resveratrol.
AB  - Survivin is a member of the inhibitor of apoptosis proteins that is expressed at
      high levels in most human cancers and may facilitate evasion from apoptosis and
      aberrant mitotic progression. Naturally occurring dietary compounds such as
      resveratrol have gained considerable attention as cancer chemopreventive agents.
      Here, we discovered a novel function of the chemopreventive agent resveratrol:
      resveratrol is a potent sensitizer of tumor cells for tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-induced apoptosis through p53
      independent induction of p21 and p21-mediated cell cycle arrest associated with
      survivin depletion. Concomitant analysis of cell cycle, survivin expression, and
      apoptosis revealed that resveratrol-induced G(1) arrest was associated with down
      regulation of survivin expression and sensitization for TRAIL-induced apoptosis.
      Accordingly, G(1) arrest using the cell cycle inhibitor mimosine or induced by
      p21 overexpression reduced survivin expression and sensitized cells for TRAIL
      treatment. Likewise, resveratrol-mediated cell cycle arrest followed by survivin
      depletion and sensitization for TRAIL was impaired in p21- deficient cells. Also,
      down-regulation of survivin using survivin antisense oligonucleotides sensitized
      cells for TRAIL-induced apoptosis. Importantly, resveratrol sensitized various
      tumor cell lines, but not normal human fibroblasts, for apoptosis induced by
      death receptor ligation or anticancer drugs. Thus, this combined sensitizer
      (resveratrol)/inducer (e.g., TRAIL) strategy may be a novel approach to enhance
      the efficacy of TRAIL-based therapies in a variety of human cancers.

PMID- 14729644
TI  - Quantitative proteomic analysis of proteins released by neoplastic prostate
      epithelium.
AB  - Prostate cancer is unusual among neoplasms in that it may be diagnosed at a
      curable stage through detection of a protein in serum, the serine protease
      prostate-specific antigen (PSA). PSA is secreted by both normal and neoplastic
      prostate epithelial cells in response to androgenic hormones and has found
      widespread use in cancer screening. Because PSA screening is controversial due to
      sensitivity and specificity issues, efforts continue to focus on the
      identification and characterization of additional markers that may be used for
      diagnostic and therapeutic purposes. In this study, we report the application of
      quantitative proteomic techniques that incorporate isotope coded affinity tag
      reagents and tandem mass spectrometry to comprehensively identify secreted and
      cell surface proteins from neoplastic prostate epithelium. LNCaP cells, a
      prostate tumor-derived cell line that secretes PSA in response to androgen
      exposure, were grown in a low protein-defined media under androgen-stimulated
      (A+) and -starved (A-) conditions. Proteomic analysis of the media identified in
      excess of 600 proteins, 524 of which could be quantified. Nine percent of the
      proteins had A+/A- ratios > 2.0, including PSA, and 2.5% had ratios < 0.5. A
      subset of these androgen-regulated proteins appeared to be expressed in
      abundance. Of these, selected mass spectrometry observations were confirmed by
      Western analysis. The findings suggest that androgen-mediated release of proteins
      may occur through the activation of proteolytic enzymes rather than exclusively
      through transcriptional or translational control mechanisms. On the basis of
      their known functional roles, several of the abundant androgen-regulated proteins
      may participate in the progression of neoplastic epithelial cell growth and
      should be considered as potential serum markers of neoplastic prostate diseases.

PMID- 14729645
TI  - Molecular determinants of the cytotoxicity of platinum compounds: the
      contribution of in silico research.
AB  - Gene expression profiling of tumors allows the establishment of relationships
      between gene expression profiles and sensitivity to anticancer drugs. In an
      attempt to study the molecular determinants of the activity of platinum
      compounds, we explored the publicly available databases of the National Cancer
      Institute (NCI; http://dtp.nci.nih.gov), which allow access to the gene
      expression profiles of the 60 cell lines for which drug cytotoxicity patterns
      already existed. Using this database, we have conducted an in silico research to
      identify the genes the expression of which was positively or negatively
      correlated to the sensitivity to four platinum compounds (cisplatin, carboplatin,
      oxaliplatin and tetraplatin). Important similarities were noticed between
      cisplatin and carboplatin on one hand, and tetraplatin and oxaliplatin on the
      other hand. In the restricted panel of 1416 genes and molecular markers, we
      identified 204 markers, among which 120 corresponded to identified genes, that
      significantly correlated (P < 0.001) with the cytotoxicity of at least one
      platinum compound. For example, the functionality of the p53-activated pathway
      appeared positively correlated with the cytotoxicity of all platinum compounds.
      More specific are the positive correlations between RAS gene mutations and MYC
      expression and the cellular sensitivity to oxaliplatin. Among the parameters
      already known as related to the sensitivity to platinum compounds, we identified,
      in the complete set of 9400 genes, numerous significant relationships, such as
      the negative correlations between ERB-B2 and BCL-X(L) expressions and the
      cytotoxicity of the platinum compounds. Public databases mining, therefore,
      appears to be a valuable tool for the identification of determinants of
      anticancer drug activity in tumors.

PMID- 14729646
TI  - Development of a cancer-targeted tissue-specific promoter system.
AB  - Present cancer gene therapy using proapoptotic genes has had limited success
      because the therapy is prone to cause side effects as a result of the lack of
      tissue and cancer specificity. To target cancer cells without damaging normal
      cells, we have designed a novel dual promoter system in which a tissue-specific
      transcription system under the control of a cancer-specific promoter drives
      expression of a therapeutic gene. The applicability of this system was
      demonstrated by adapting it to target lung cancer. We termed this lung cancer
      system TTS (TTF1 gene under the control of human telomerase reverse transcriptase
      promoter and human surfactant protein A1 promoter). The TTS system showed much
      higher promoter activity in lung cancer cells compared with other kinds of cancer
      and normal lung cells, including stem cells. Moreover, insertion of negative
      glucocorticoid responsive elements in the system allows it to be drug
      controllable. The approaches that we have used could be adapted to target other
      types of cancer. We report a novel cancer-targeted tissue-specific dual promoter
      system designed for gene therapy.

PMID- 14729647
TI  - Retinoblastoma protein and CCAAT/enhancer-binding protein beta are required for
      1,25-dihydroxyvitamin D3-induced monocytic differentiation of HL60 cells.
AB  - Derivatives of vitamin D (deltanoids) are well known to have the ability to
      induce differentiation of a variety of malignant cells, including human leukemia
      cells, but the signaling pathways that lead to such an outcome are unclear. In
      this study we investigated the role of the retinoblastoma protein (pRb) and the
      CCAAT/enhancer-binding protein (C/EBP) beta in 1,25-dihydroxyvitamin D(3)
      (1,25D(3))-induced monocytic differentiation of human leukemia HL60 cells. It was
      found that in this system, pRb is up-regulated within 12 h of exposure to the
      inducer, and the kinetics of its increase parallel the appearance of the early
      markers of differentiation, CD14 and monocyte-specific esterase. The increase in
      pRb expression was accompanied by a similar increase in C/EBPbeta protein, and
      these two proteins coimmunoprecipitated, suggesting formation of a complex.
      Oligonucleotides antisense to pRb or C/EBPbeta (but not to C/EBPalpha) or
      containing the C/EBP-binding sequence ("decoys"), all inhibited 1,25D(3)-induced
      differentiation. Inhibition of signaling by vitamin D receptor or by mitogen
      activated protein kinase (MAPK) extracellular signal-regulated kinase and c-Jun
      NH(2)-terminal kinase pathways using pharmacological inhibitors ZK159222,
      PD98059, or SP600125, respectively, inhibited pRb and C/EBPbeta expression and
      differentiation in a coordinate manner. In contrast, inhibition of the p38MAPK
      pathway by SB202190 potentiated differentiation and the up-regulation of pRb and
      C/EBPbeta. We suggest that 1,25D(3) may signal monocytic differentiation of HL60
      cells in a vitamin D receptor-dependent manner that includes activation of
      extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase MAPK
      pathways, which then up-regulate pRb and C/EBPbeta expression and in turn
      initiate the differentiation process.

PMID- 14729648
TI  - Effect of human natural killer and gammadelta T cells on the growth of human
      autologous melanoma xenografts in SCID mice.
AB  - Natural killer (NK) cells were first identified for their ability to kill tumor
      cells of different origin in vitro. Similarly, gammadelta T lymphocytes display
      strong cytotoxic activity against various tumor cell lines. However, the ability
      of both the NK and gammadelta cells to mediate natural immune response against
      human malignant tumors in vivo is still poorly defined. Severe combined
      immunodeficient (SCID) mice have been successfully engrafted with human tumors.
      In this study, the antitumor effect of local as well as of systemic treatments
      based on NK cells or Vdelta1 or Vdelta2 gamma/delta T lymphocytes against
      autologous melanoma cells was investigated in vivo. The results show that all
      three of the populations were effective in preventing growth of autologous human
      melanomas when both tumor and lymphoid cells were s.c. inoculated at the same
      site. However, when lymphoid cells were infused i.v., only NK cells and Vdelta1
      gamma/delta T lymphocytes could either prevent or inhibit the s.c. growth of
      autologous melanoma. Accordingly, both NK cells and Vdelta1 gammadelta T
      lymphocytes could be detected at the s.c. tumor site. In contrast, Vdelta2
      gammadelta T lymphocytes were only detectable in the spleen of the SCID mice.
      Moreover, NK cells maintained their inhibitory effect on tumor growth even after
      discontinuation of the treatment. Indeed they were present at the tumor site for
      a longer period. These data support the possibility to exploit NK cells and
      Vdelta1 gammadelta T lymphocytes in tumor immunotherapy. Moreover, our study
      emphasizes the usefulness of human tumor/SCID mouse models for preclinical
      evaluation of immunotherapy protocols against human tumors.

PMID- 14729649
TI  - Potentiation of tumor eradication by adoptive immunotherapy with T-cell receptor
      gene-transduced T-helper type 1 cells.
AB  - Adoptive immunotherapy using antigen-specific T-helper type 1 (Th1) cells has
      been considered as a potential strategy for tumor immunotherapy. However, its
      application to tumor immunotherapy has been hampered by difficulties in expanding
      tumor-specific Th1 cells from tumor-bearing hosts. Here, we have developed an
      efficient protocol for preparing mouse antigen-specific Th1 cells from
      nonspecifically activated Th cells after retroviral transfer of T-cell receptor
      (TCR)-alpha and TCR-beta genes. We demonstrate that Th1 cells transduced with the
      TCR-alpha and -beta genes from the I-A(d)-restricted ovalbumin (OVA)(323-339)
      specific T-cell clone DO11.10 produce IFN-gamma but not interleukin-4 in response
      to stimulation with OVA(323-339) peptides or A20 B lymphoma (A20-OVA) cells
      expressing OVA as a model tumor antigen. TCR-transduced Th1 cells also exhibited
      cytotoxicity against tumor cells in an antigen-specific manner. Moreover,
      adoptive transfer of TCR-transduced Th1 cells, but not mock-transduced Th1 cells,
      exhibited potent antitumor activity in vivo and, when combined with
      cyclophosphamide treatment, completely eradicated established tumor masses. Thus,
      TCR-transduced Th1 cells are a promising alternative for the development of
      effective adoptive immunotherapies.

PMID- 14729650
TI  - Graft-versus-Tax response in adult T-cell leukemia patients after hematopoietic
      stem cell transplantation.
AB  - Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I)
      is characterized by poor prognosis after chemotherapy. Recent clinical trials
      have indicated, however, that allogeneic but not autologous hematopoietic stem
      cell transplantation (HSCT) for ATL can yield better clinical outcomes. In the
      present study, we investigated cellular immune responses of ATL patients who
      obtained complete remission after nonmyeloablative allogeneic peripheral blood
      HSCT from HLA-identical sibling donors. In the culture of peripheral blood
      mononuclear cells (PBMCs) from a post-HSCT but not pre-HSCT ATL patient, CD8(+)
      CTLs proliferated vigorously in response to stimulation with autologous HTLV-I
      infected T cells that had been established before HSCT in vitro. These CTLs
      contained a large number of monospecific CTL population directed to a HLA-A2
      restricted HTLV-I Tax 11-19 epitope. The frequency of Tax 11-19-specific CD8+
      CTLs in this patient markedly increased also in vivo after HSCT, as determined by
      staining with HLA-A2/Tax 11-19 tetramers. Similar clonal expansion of HTLV-I Tax
      specific CTLs exclusively directed to a HLA-A24-restricted Tax 301-309 epitope
      was observed in the PBMCs from another ATL patient after HSCT from a HTLV-I
      negative donor. Among four post-HSCT ATL patients tested, HTLV-I-specific CTLs
      were induced in the PBMC culture from three patients but not from the remaining
      one who had later recurrence of ATL. These observations suggested that
      reconstituted immunity against antigen presentation in ATL patients after HSCT
      resulted in strong and selective graft-versus-HTLV-I response, which might
      contribute to graft-versus-leukemia effects.

PMID- 14729651
TI  - Enhancement of DNA vaccine potency by coadministration of a tumor antigen gene
      and DNA encoding serine protease inhibitor-6.
AB  - Serine protease inhibitor 6 (SPI-6), also called Serpinb9, inhibits granzyme B
      and thus may provide a method for delaying apoptotic cell death in dendritic
      cells. We have previously enhanced DNA vaccine potency by targeting antigen to
      MHC antigen presentation pathways, using proteins such as Mycobacterium
      tuberculosis heat shock protein 70, calreticulin, domain II of Pseudomonas
      aeruginosa exotoxin A, or the sorting signal of the lysosome-associated membrane
      protein type 1. In this study, we explored intradermal coadministration of DNA
      encoding SPI-6 with DNA constructs encoding human papillomavirus type 16 E7
      linked to these intracellular targeting molecules for its ability to generate E7
      specific CD8+ T-cell immune responses and E7-specific antitumor effects. This
      combination of strategies resulted in significantly increased E7-specific CD8+ T
      cell and CD4+ Th1-cell responses, enhanced tumor treatment ability, and stronger
      tumor protection when compared with vaccination without SPI-6. Among these
      targeting strategies tested, mice vaccinated with Sig/E7/lysosome-associated
      membrane protein type 1 mixed with SPI-6 showed the greatest fold increase in E7
      specific CD8+ T cells ( approximately 5-fold). Vaccination with a nonfunctional
      mutant of SPI-6 did not result in immune enhancement, indicating that enhancement
      was dependent on the antiapoptotic function of SPI-6. Our results suggest that
      DNA vaccines combining strategies that enhance MHC class I and II antigen
      processing with SPI-6 have potential clinical implications for control of viral
      infection and neoplasia.

PMID- 14729652
TI  - Effector cell-derived lymphotoxin alpha and Fas ligand, but not perforin, promote
      Tc1 and Tc2 effector cell-mediated tumor therapy in established pulmonary
      metastases.
AB  - Cytolytic CD8(+) effector cells fall into two subpopulations based on cytokine
      secretion. Type 1 CD8(+) T cells (Tc1) secrete IFN-gamma, whereas type 2 CD8(+) T
      cells (Tc2) secrete interleukin (IL)-4 and IL-5. Although both effector cell
      subpopulations display Fas ligand (FasL) and tumor necrosis factor (TNF), tumor
      lysis is predominantly perforin dependent in vitro. Using an ovalbumin
      transfected B16 lung metastasis model, we show that heightened numbers of
      adoptively transferred ovalbumin-specific Tc1 and Tc2 cells accumulated at the
      tumor site by day 2 after therapy and induced tumor regression that enhanced
      survival in mice with pulmonary metastases. Transfer of either TNF-alpha- or
      perforin-deficient Tc1 or Tc2 effector cells generated from specified gene
      deficient mice showed no differences in therapeutic efficiency when compared with
      corresponding wild-type cells. In contrast, both Tc1 and Tc2 cells, derived from
      either FasL or TNF-alpha/lymphotoxin (LT) alpha double knockout mice, showed that
      therapeutic effects were dependent, in part, on effector cell-derived FasL or
      LTalpha. Six days after effector cell therapy, elevated levels of activated
      endogenous CD8/CD44(High) and CD4/CD44(High) T cells localized and persisted at
      sites of tumor growth, whereas donor cell numbers concomitantly decreased. Both
      Tc1 and Tc2 effector cell subpopulations induced endogenous antitumor responses
      that were dependent, in part, on recipient-derived IFN-gamma and TNF-alpha.
      However, neither effector cell-mediated therapy was dependent on recipient
      derived perforin, IL-4, IL-5, or nitric oxide. Collectively, tumor antigen
      specific Tc1 and Tc2 effector cell-mediated therapy is initially dependent, in
      part, on effector cell-derived FasL or LTalpha that may subsequently potentiate
      endogenous recipient-derived type 1 antitumor responses dependent on TNF-alpha
      and IFN-gamma.

PMID- 14729653
TI  - Systemic retinoic acid treatment induces sodium/iodide symporter expression and
      radioiodide uptake in mouse breast cancer models.
AB  - Lactating breast tissue and some breast cancers express the sodium/iodide
      symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans
      retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in
      vitro in well-differentiated human breast cancer cells (MCF-7). In the present
      study, we investigated the in vivo efficacy and specificity of tRA-stimulated
      iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF
      7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation
      in the xenograft tumors was markedly increased, approximately 15-fold greater
      than levels without treatment, and the effects were tRA dose dependent. Iodide
      accumulation in other organs was not significantly influenced by tRA treatment.
      Significant induction of NIS mRNA and protein in the xenograft tumors was
      observed after tRA treatment. Iodide accumulation and NIS mRNA expression were
      also selectively induced in breast cancer tissues in transgenic mice expressing
      the oncogene, polyoma virus middle T antigen. These data demonstrate selective
      induction of functional NIS in breast cancer by tRA. Treatment with short-term
      systemic retinoic acid, followed by radioiodide administration, is a potential
      tool in the diagnosis and treatment of some differentiated breast cancer.

PMID- 14729654
TI  - Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor
      formation by causing a G2 cell cycle arrest.
AB  - Studies indicate that estrogen receptor (ER) alpha mediates breast cancer
      promoting effects of estrogens. The role of ERbeta in breast cancer is unknown.
      Elucidating the role of ERbeta in the pathogenesis of breast cancer is important
      because many human breast tumors express both ERalpha and ERbeta. We show that
      adenovirus-mediated expression of ERbeta changes the phenotype of ERalpha
      positive MCF-7 cells. Estradiol increases cell proliferation and causes tumor
      formation of MCF-7 cells expressing only ERalpha. In contrast, introducing ERbeta
      into MCF-7 cells causes an inhibition of proliferation in vitro and prevents
      tumor formation in a mouse xenograft model in response to estradiol. ERbeta
      inhibits proliferation by repressing c-myc, cyclin D1, and cyclin A gene
      transcription, and increasing the expression of p21(Cip1) and p27(Kip1), which
      leads to a G(2) cell cycle arrest. These results demonstrate that ERalpha and
      ERbeta produce opposite effects in MCF-7 cells on cell proliferation and tumor
      formation. Natural or synthetic ERbeta-selective estrogens may lack breast cancer
      promoting properties exhibited by estrogens in hormone replacement regimens and
      may be useful for chemoprevention of breast cancer.

PMID- 14729655
TI  - The drug salicylamide is an antagonist of the aryl hydrocarbon receptor that
      inhibits signal transduction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental
      contaminant, that has been linked with a variety of deleterious effects on human
      health, including increased cancer rates and reproductive anomalies. The
      detrimental effects of TCDD are mediated via the aryl hydrocarbon receptor (AhR),
      a transcription factor that regulates the expression of the carcinogen-activating
      enzymes cytochromes P-450 (CYP) 1A1, 1A2, and 1B1. In the present study, we
      examined the ability of synthetic derivatives of salicylic acid to affect TCDD
      stimulated AhR-mediated signal transduction in human hepatoma HepG2 cells.
      Salicylamide (SAL), an analgesic drug, caused a potent and long-lasting
      inhibition of TCDD-induced CYP enzyme activity. Acetylsalicylic acid (aspirin)
      and the naturally occurring phytochemical salicylic acid had no effect on CYP
      activity. SAL inhibited the increase in CYP1A1, -1A2, and -1B1 mRNA levels that
      occurs on exposure to TCDD. TCDD-induced transcription of these genes was also
      inhibited by SAL, but not by aspirin or salicylic acid, as demonstrated by
      luciferase reporter assays. The transcription of the CYP1 family of genes is
      regulated by the interaction of TCDD-activated AhR with the xenobiotic-responsive
      element present in the promoter regions of these genes. As shown by
      electrophoretic mobility shift assay, SAL completely blocked the binding of TCDD
      activated AhR to the xenobiotic responsive element. Also, SAL substantially
      blocked the binding of TCDD to the cytosolic AhR. These results demonstrate that
      SAL, a commonly used analgesic, is a potent inhibitor of AhR-mediated signal
      transduction, and may be an effective agent in the prevention of TCDD-associated
      disease.

PMID- 14729656
TI  - Exercise training meta-analysis of trials in patients with chronic heart failure
      (ExTraMATCH).
AB  - OBJECTIVE: To determine the effect of exercise training on survival in patients
      with heart failure due to left ventricular systolic dysfunction. DESIGN:
      Collaborative meta-analysis. Inclusion criteria Randomised parallel group
      controlled trials of exercise training for at least eight weeks with individual
      patient data on survival for at least three months. Studies reviewed Nine
      datasets, totalling 801 patients: 395 received exercise training and 406 were
      controls. MAIN OUTCOME MEASURE: Death from all causes. RESULTS: During a mean
      (SD) follow up of 705 (729) days there were 88 (22%) deaths in the exercise arm
      and 105 (26%) in the control arm. Exercise training significantly reduced
      mortality (hazard ratio 0.65, 95% confidence interval, 0.46 to 0.92; log rank
      chi(2) = 5.9; P = 0.015). The secondary end point of death or admission to
      hospital was also reduced (0.72, 0.56 to 0.93; log rank chi(2) = 6.4; P = 0.011).
      No statistically significant subgroup specific treatment effect was observed.
      CONCLUSION: Meta-analysis of randomised trials to date gives no evidence that
      properly supervised medical training programmes for patients with heart failure
      might be dangerous, and indeed there is clear evidence of an overall reduction in
      mortality. Further research should focus on optimising exercise programmes and
      identifying appropriate patient groups to target.

PMID- 14729657
TI  - Effectiveness of opportunistic brief interventions for problem drinking in a
      general hospital setting: systematic review.
AB  - OBJECTIVE: To determine the effectiveness of opportunistic brief interventions
      for problem drinking in a general hospital setting. DESIGN: Systematic review.
      DATA SOURCES: Medline, PsychInfo, Cochrane Library, reference lists from
      identified studies and review articles, and contact with experts. MAIN OUTCOME
      MEASURE: Change in alcohol consumption. RESULTS: Eight studies were retrieved.
      Most had methodological weaknesses. Only one study, with a relatively intensive
      intervention and a short follow up period, showed a significantly large reduction
      in alcohol consumption in the intervention group. CONCLUSIONS: Evidence for the
      effectiveness of opportunistic brief interventions in a general hospital setting
      for problem drinkers is still inconclusive.

PMID- 14729658
TI  - 186Rhenium-labeled anti-CD20 antibody radioimmunotherapy followed by autologous
      peripheral blood stem cell transplantation in patients with relapsed or
      refractory non-Hodgkin lymphoma.

PMID- 14729659
TI  - Granzyme A: an additional weapon of human polymorphonuclear neutrophils (PMNs) in
      innate immunity?

PMID- 14729660
TI  - mRNA is an endogenous ligand for Toll-like receptor 3.
AB  - Toll-like receptors (TLRs) are the basic signaling receptors of the innate immune
      system. They are activated by molecules associated with pathogens or injured host
      cells and tissue. TLR3 has been shown to respond to double stranded (ds) RNA, a
      replication intermediary for many viruses. Here we present evidence that
      heterologous RNA released from or associated with necrotic cells or generated by
      in vitro transcription also stimulates TLR3 and induces immune activation. To
      assess RNA-mediated TLR3 activation, human embryonic kidney 293 cells stably
      expressing TLR3 and containing a nuclear factor-kappaB-dependent luciferase
      reporter were generated. Exposing these cells to in vitro transcribed RNA
      resulted in a TLR3-dependent induction of luciferase activity and interleukin-8
      secretion. Treatment with in vitro transcribed mRNA activated nuclear factor
      kappaB via TLR3 through a process that was dose-dependent and involved tyrosine
      phosphorylation. Furthermore, in vitro transcribed natural or 2'-fluoro
      substituted mRNA induced the expression of TLR3, interferon regulatory factor-1,
      tumor necrosis factor-alpha, and interleukin-1 receptor-associated kinase-M mRNA
      in human dendritic cells (DCs). DCs responded to mRNA treatment by expressing
      activation markers, and this maturation was inhibited by antagonistic TLR3
      specific antibody. Endogenous RNA released from or associated with necrotic cells
      also stimulated DCs, leading to interferon-alpha secretion, which could be
      abolished by pretreatment of necrotic cells with RNase. These results demonstrate
      that RNA, likely through secondary structure, is a potent host-derived activator
      of TLR3. This finding has potential physiologic relevance because RNA escaping
      from damaged tissue or contained within endocytosed cells could serve as an
      endogenous ligand for TLR3 that induces or otherwise modulates immune responses.

PMID- 14729661
TI  - Expression of caveolin-1 enhances cholesterol efflux in hepatic cells.
AB  - HepG2 cells were stably transfected with human caveolin-1 (HepG2/cav cells).
      Transfection resulted in expression of caveolin-1 mRNA, a high abundance of
      caveolin-1 protein, and the formation of caveolae on the plasma membrane.
      Cholesterol efflux from HepG2/cav cells was 280 and 45% higher than that from
      parent HepG2 cells when human plasma and human apoA-I, respectively, were used as
      acceptors. The difference in efflux was eliminated by treatment of cells with
      progesterone. There was no difference in cholesterol efflux to cyclodextrin.
      Cholesterol efflux from plasma membrane vesicles was similar for the two cell
      types. Transfection led to a 40% increase in the amount of plasma membrane
      cholesterol in cholesterol-rich domains (caveolae and/or rafts) and a 67%
      increase in the rate of cholesterol trafficking from intracellular compartments
      to these domains. Cholesterol biosynthesis in HepG2/cav cells was increased by 2
      fold, and cholesterol esterification was reduced by 50% compared with parent
      HepG2 cells. The proliferation rate of transfected cells was significantly lower
      than that of non-transfected cells. Transfection did not affect expression of
      ABCA1 or the abundance of ABCA1 protein, but decreased secretion of apoA-I. We
      conclude that overexpression of caveolin-1 in hepatic cells stimulates
      cholesterol efflux by enhancing transfer of cholesterol to cholesterol-rich
      domains in the plasma membrane.

PMID- 14729662
TI  - Hierarchical formation of disulfide bonds in the immunoglobulin Fc fragment is
      assisted by protein-disulfide isomerase.
AB  - Antibodies provide an excellent system to study the folding and assembly of all
      beta-sheet proteins and to elucidate the hierarchy of intra/inter chain disulfide
      bonds formation during the folding process of multimeric and multidomain
      proteins. Here, the folding process of the Fc fragment of the heavy chain of the
      antibody MAK33 was investigated. The Fc fragment consists of the C(H)3 and C(H)2
      domains of the immunoglobulin heavy chain, both containing a single S-S bond. The
      folding process was investigated both in the absence and presence of the folding
      catalyst protein-disulfide isomerase (PDI), monitoring the evolution of
      intermediates by electrospray mass spectrometry. Moreover, the disulfide bonds
      present at different times in the folding mixture were identified by mass mapping
      to determine the hierarchy of disulfide bond formation. The analysis of the
      uncatalyzed folding showed that the species containing one intramolecular
      disulfide predominated throughout the entire process, whereas the fully oxidized
      Fc fragment never accumulated in significant amounts. This result suggests the
      presence of a kinetic trap during the Fc folding, preventing the one-disulfide
      containing species (1S2H) to reach the fully oxidized protein (2S). The
      assignment of disulfide bonds revealed that 1S2H is a homogeneous species
      characterized by the presence of a single disulfide bond (Cys-130-Cys-188)
      belonging to the C(H)3 domain. When the folding experiments were carried out in
      the presence of PDI, the completely oxidized species accumulated and predominated
      at later stages of the process. This species contained the two native S-S bonds
      of the Fc protein. Our results indicate that the two domains of the Fc fragment
      fold independently, with a precise hierarchy of disulfide formation in which the
      disulfide bond, especially, of the C(H)2 domain requires catalysis by PDI.

PMID- 14729664
TI  - Activation of glycogen phosphorylase with 5-aminoimidazole-4-carboxamide riboside
      (AICAR). Assessment of glycogen as a precursor of mannosyl residues in
      glycoconjugates.
AB  - The experimental evaluation of the contribution of glycogen phosphorylase (GP) to
      biochemical pathways is limited to methods that raise cAMP, activating the cAMP
      dependent protein kinase/phosphorylase kinase/GP cascade. Such methods convert
      the unphosphorylated form, "GPb," which catalyzes glycogenolysis only in the
      presence of appropriate allosteric activators such as AMP, to the phosphorylated,
      constitutively activated form, "GPa." However, activation of GP in this way is
      indirect, requires a functional cAMP kinase cascade, and is complicated by other
      actions of cAMP. Here, we demonstrate a strategy for the experimental
      manipulation of GP in intact dermal fibroblasts, involving activation by the
      membrane-permeable adenosine analog 5-aminoimidazole-4-carboxamide riboside
      (AICAR) and inhibition by caffeine and Pfizer compound CP-91149, which bind to GP
      at distinct sites. Potential complications because of activation of AMP-activated
      protein kinase by AICAR were assessed with metformin, which activates this kinase
      but does not activate GP. Using this strategy, we show that glycogen can be a
      significant and regulatable precursor of mannosyl units in lipid-linked
      oligosaccharides and glycoproteins.

PMID- 14729663
TI  - Recruitment of the actin-binding protein HIP-55 to the immunological synapse
      regulates T cell receptor signaling and endocytosis.
AB  - Actin cytoskeleton dynamics critically regulate T cell activation. We found that
      the cytoplasmic adaptor HIP-55, a Src/Syk-kinases substrate and member of the
      drebrin/Abp1 family of actin-binding proteins, localized to the T cell-antigen
      presenting cell (APC) contact site in an antigen-dependent manner. Using green
      fluorescent protein fusion proteins, both Src homology 3 (SH3) and actin binding
      domains were found necessary for recruitment at the T cell-APC interface. HIP-55
      was not implicated in conjugate formation and actin polymerization but regulated
      distal signaling events through binding and activation of hematopoietic
      progenitor kinase 1 (HPK1), a germinal center kinase (GCK) family kinase involved
      in negative signaling in T cells. Using RNA interference and overexpression
      experiments, the HIP-55-HPK1 complex was found to negatively regulate nuclear
      factor of activated T cell (NFAT) activation by the T cell antigen receptor.
      Moreover, we show that HIP-55, which partly co-localized with early endocytic
      compartments, promoted both basal and ligand-dependent T cell receptor (TCR) down
      modulation, resulting in a decreased TCR expression. SH3 and actin-depolymerizing
      factor homology domains were required for this function. As controls, the
      expression of CD28 and the glycosylphosphatidylinositol-linked protein CD59 was
      not affected by HIP-55 overexpression. These results suggest that, in addition to
      binding to HPK1, HIP-55 might negatively regulate TCR signaling through down
      regulation of TCR expression. Our findings show that HIP-55 is a key novel
      component of the immunological synapse that modulates T cell activation by
      connecting actin cytoskeleton and TCRs to gene activation and endocytic
      processes.

PMID- 14729665
TI  - Domain organization of phytochelatin synthase: functional properties of truncated
      enzyme species identified by limited proteolysis.
AB  - Phytochelatin synthase (PCS) is a major determinant of heavy metal tolerance in
      plants and other organisms. No structural information on this enzyme is as yet
      available. It is generally believed, however, that the active site region is
      located in the more conserved N-terminal portion of PCS, whereas various, as yet
      unidentified (but supposedly less critical) roles have been proposed for the C
      terminal region. To gain insight into the structural/functional organization of
      PCS, we have conducted a limited proteolysis analysis of the enzyme from
      Arabidopsis (AtPCS1), followed by functional characterization of the resulting
      polypeptide fragments. Two N-terminal fragments ending at positions 372 (PCS_Nt1)
      and 283 (PCS_Nt2) were produced sequentially upon V8 protease digestion, without
      any detectable accumulation of the corresponding C-terminal fragments. As
      revealed by the results of in vivo and in vitro functional assays, the core
      PCS_Nt2 fragment is biosynthetically active in the presence of cadmium ions and
      supports phytochelatin formation at a rate that is only approximately 5-fold
      lower than that of full-length AtPCS1. The loss of the C-terminal region,
      however, substantially decreases the thermal stability of the enzyme and impairs
      phytochelatin formation in the presence of certain heavy metals (e.g. mercury and
      zinc, but not cadmium or copper). The latter phenotype was shared by PCS_Nt2 and
      by its precursor fragment PCS_Nt1, which, on the other hand, was almost as stable
      and biosynthetically active (in the presence of cadmium) as the full-length
      enzyme. AtPCS1 thus appears to be composed of a protease-resistant (and hence
      presumably highly structured) N-terminal domain, flanked by an intrinsically
      unstable C-terminal region. The most upstream part of such a region (positions
      284-372) is important for enzyme stabilization, whereas its most terminal part
      (positions 373-485) appears to be required to determine enzyme responsiveness to
      a broader range of heavy metals.

PMID- 14729666
TI  - The role of tyrosine 343 in substrate binding and catalysis by human sulfite
      oxidase.
AB  - In the crystal structure of chicken sulfite oxidase, the residue Tyr(322)
      (Tyr(343) in human sulfite oxidase) was found to directly interact with a bound
      sulfate molecule and was proposed to have an important role in mediating the
      substrate specificity and catalytic activity of this molybdoprotein. In order to
      understand the role of this residue in the catalytic mechanism of sulfite
      oxidase, steady-state and stopped-flow analyses were performed on wild-type and
      Y343F human sulfite oxidase over the pH range 6-10. In steady-state assays of
      Y343F sulfite oxidase using cytochrome c as the electron acceptor, k(cat) was
      somewhat impaired ( approximately 34% wild-type activity at pH 8.5), whereas the
      K(m)(sulfite) showed a 5-fold increase over wild type. In rapid kinetic assays of
      the reductive half-reaction of wild-type human sulfite oxidase, k(red)(heme)
      changed very little over the entire pH range, with a significant increase in
      K(d)(sulfite) at high pH. The k(red)(heme) of the Y343F variant was significantly
      impaired across the entire pH range, and unlike the wild-type protein, both
      k(red)(heme) and K(d)(sulfite) were dependent on pH, with a significant increase
      in both kinetic parameters at high pH. Additionally, reduction of the molybdenum
      center by sulfite was directly measured for the first time in rapid reaction
      assays using sulfite oxidase lacking the N-terminal heme-containing domain.
      Reduction of the molybdenum center was quite fast (k(red)(Mo) = 972 s(-1) at pH
      8.65 for wild-type protein), indicating that this is not the rate-limiting step
      in the catalytic cycle. Reduction of the molybdenum center of the Y343F variant
      by sulfite was more significantly impaired at high pH than at low pH. These
      results demonstrate that the Tyr(343) residue is important for both substrate
      binding and oxidation of sulfite by sulfite oxidase.

PMID- 14729667
TI  - The Bacillus subtilis counterpart of the mammalian 3-methyladenine DNA
      glycosylase has hypoxanthine and 1,N6-ethenoadenine as preferred substrates.
AB  - The AAG family of 3-methyladenine DNA glycosylases was initially thought to be
      limited to mammalian cells, but genome sequencing efforts have revealed the
      presence of homologous proteins in certain prokaryotic species as well. Here, we
      report the first molecular characterization of a functional prokaryotic AAG
      homologue, i.e. YxlJ, termed bAag, from Bacillus subtilis. The B. subtilis aag
      gene was expressed in Escherichia coli, and the protein was purified to
      homogeneity. As expected, B. subtilis Aag was found to be a DNA glycosylase,
      which releases 3-alkylated purines and hypoxanthine, as well as the cyclic etheno
      adduct 1,N(6)-ethenoadenine from DNA. However, kinetic analysis showed that bAag
      removed hypoxanthine much faster than human AAG with a 10-fold higher value for
      k(cat), whereas the rate of excision of 1, N(6)-ethenoadenine was found to be
      similar. In contrast, it was found that bAag removes 3-methyladenine and 3
      methylguanine approximately 10-20 times more slowly than human AAG, and there was
      hardly any detectable excision of 7-methylguanine. It thus appears that bAag has
      a minor role in the repair of DNA alkylation damage and an important role in
      preventing the mutagenic effects of deaminated purines and cyclic etheno adducts
      in Bacillus subtilis.

PMID- 14729668
TI  - The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate
      dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase
      domain.
AB  - 10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate,
      a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein
      comprises two functional domains: a hydrolase domain that removes a formyl group
      from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that
      reduces the formyl to carbon dioxide. As a first step toward deciphering the
      catalytic mechanism of the enzyme, we have determined the crystal structure of
      the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure
      comprises two domains. As expected, domain 1 shares the same Rossmann fold as the
      related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide
      formyltransferase, but, unexpectedly, the structural similarity between the amino
      terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA
      formyltransferase extends to the C terminus of both proteins. The active site
      contains a molecule of beta-mercaptoethanol that is positioned between His-106
      and Asp-142 and that appears to mimic the formate product. We propose a catalytic
      mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic
      water molecule and His-106 orients the carbonyl group of formyl. The structure
      also provides clues as to how, in the native enzyme, the hydrolase domain
      transfers its product to the dehydrogenase domain.

PMID- 14729669
TI  - Trigger factor peptidyl-prolyl cis/trans isomerase activity is not essential for
      the folding of cytosolic proteins in Escherichia coli.
AB  - The ribosome-associated Trigger Factor (TF) cooperates with the DnaK system to
      assist the folding of newly synthesized polypeptides in Escherichia coli. TF
      unifies two functions in one to promote proper protein folding in vitro. First,
      as a chaperone it binds to unfolded protein substrates, thereby preventing
      aggregation and supporting productive folding. Second, TF catalyzes the cis/trans
      isomerization of peptidyl-prolyl bonds, which can be a rate-limiting step in
      protein folding. Here, we investigated whether the peptidyl-prolyl cis/trans
      isomerase (PPIase) function is essential for the folding activity of TF in vitro
      and in vivo by separating these two TF activities through site-directed
      mutagenesis of the PPIase catalytic center. Of the four different TF variants
      carrying point mutations in the PPIase domain, only the exchange of the conserved
      residue Phe-198 to Ala (TF F198A) abolished the PPIase activity of TF toward both
      a tetrapeptide and the model protein substrate RNase T1 in vitro. In contrast,
      all other activities of TF F198A tested were comparable with wild type TF. TF
      F198A retained a similar binding specificity toward membrane-bound peptides,
      assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in
      vitro, and associated with nascent polypeptides in an in vitro
      transcription/translation system. Importantly, expression of the TF F198A
      encoding gene complemented the synthetic lethality of DeltatigDeltadnaK cells and
      prevented global protein misfolding at temperatures between 20 and 34 degrees C
      in these cells. We conclude that the PPIase activity is not required for the
      function of TF in folding of newly synthesized proteins.

PMID- 14729670
TI  - Crystal structure of the Mor protein of bacteriophage Mu, a member of the Mor/C
      family of transcription activators.
AB  - Transcription from the middle promoter, Pm, of bacteriophage Mu requires the
      phage-encoded activator protein Mor and bacterial RNA polymerase. Mor is a
      sequence-specific DNA-binding protein that mediates transcription activation
      through its interactions with the C-terminal domains of the alpha and sigma
      subunits of bacterial RNA polymerase. Here we present the first structure for a
      member of the Mor/C family of transcription activators, the crystal structure of
      Mor to 2.2-A resolution. Each monomer of the Mor dimer is composed of two
      domains, the N-terminal dimerization domain and C-terminal DNA-binding domain,
      which are connected by a linker containing a beta strand. The N-terminal
      dimerization domain has an unusual mode of dimerization; helices alpha1 and
      alpha2 of both monomers are intertwined to form a four-helix bundle, generating a
      hydrophobic core that is further stabilized by antiparallel interactions between
      the two beta strands. Mutational analysis of key leucine residues in helix alpha1
      demonstrated a role for this hydrophobic core in protein solubility and function.
      The C-terminal domain has a classical helix-turn-helix DNA-binding motif that is
      located at opposite ends of the elongated dimer. Since the distance between the
      two helix-turn-helix motifs is too great to allow binding to two adjacent major
      grooves of the 16-bp Mor-binding site, we propose that conformational changes in
      the protein and DNA will be required for Mor to interact with the DNA. The highly
      conserved glycines flanking the beta strand may act as pivot points, facilitating
      the conformational changes of Mor, and the DNA may be bent.

PMID- 14729671
TI  - Identification of the Jak/Stat proteins as novel downstream targets of EphA4
      signaling in muscle: implications in the regulation of acetylcholinesterase
      expression.
AB  - Eph receptors and their cognate ligands ephrins are important players in axon
      guidance and neural patterning during development of the nervous system. Much of
      our knowledge about the signal transduction pathways triggered by Eph receptors
      has been related to the modulation of actin cytoskeleton, which is fundamental in
      mediating the cellular responses in growth cone navigation, cell adhesion, and
      cell migration. In contrast, little was known about whether long term activation
      of Eph receptor would regulate gene expression. Here we report a novel signaling
      pathway of EphA4, which involves activation of the tyrosine kinase Jak2 and the
      transcriptional activator Stat3. Transfection of COS7 cells with EphA4, but not
      the kinase-dead mutant, induced tyrosine phosphorylation of Jak2, Stat1, and
      Stat3. Treatment of cultured C2C12 myotubes with ephrin-A1 also induced tyrosine
      phosphorylation of Stat3, which was abolished by the Jak2 inhibitor AG490.
      Moreover, Jak2 was co-immunoprecipitated with EphA4 in muscle, and both proteins
      were concentrated at the neuromuscular junction (NMJ) of adult muscle. By using
      microarray analysis, we have identified acetylcholinesterase, the critical enzyme
      that hydrolyzed the neurotransmitter acetylcholine at the NMJ, as a downstream
      target gene of the Jak/Stat pathway in muscle. More importantly, ephrin-A1
      increased the expression of acetylcholinesterase protein in C2C12 myotubes, which
      was abolished by AG490. In contrast, ephrin-A1 reduced the expression of
      fibronectin mRNA in C2C12 myotubes independently of Jak2. Finally, the expression
      level of acetylcholinesterase in limb muscle of EphA4 null mice was significantly
      reduced compared with the wild-type control. Taken together, these results have
      identified Jak/Stat proteins as the novel downstream targets of EphA4 signaling.
      In addition, the present study provides the first demonstration of a potential
      function of Eph receptors and Jak/Stat proteins at the NMJ.

PMID- 14729672
TI  - Yeast contain a non-proteinaceous pool of copper in the mitochondrial matrix.
AB  - The yeast mitochondrion is shown to contain a pool of copper that is distinct
      from that associated with the two known mitochondrial cuproenzymes, superoxide
      dismutase (Sod1) and cytochrome c oxidase (CcO) and the copper-binding CcO
      assembly proteins Cox11, Cox17, and Sco1. Only a small fraction of mitochondrial
      copper is associated with these cuproproteins. The bulk of the remainder is
      localized within the matrix as a soluble, anionic, low molecular weight complex.
      The identity of the matrix copper ligand is unknown, but the bulk of the matrix
      copper fraction is not protein-bound. The mitochondrial copper pool is dynamic,
      responding to changes in the cytosolic copper level. The addition of copper salts
      to the growth medium leads to an increase in mitochondrial copper, yet the
      expansion of this matrix pool does not induce any respiration defects. The matrix
      copper pool is accessible to a heterologous cuproenzyme. Co-localization of human
      Sod1 and the metallochaperone CCS within the mitochondrial matrix results in
      suppression of growth defects of sod2Delta cells. However, in the absence of CCS
      within the matrix, the activation of human Sod1 can be achieved by the addition
      of copper salts to the growth medium.

PMID- 14729673
TI  - Role of mediator in transcriptional activation by the aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AHR) binds many aromatic hydrocarbon compounds and
      mediates their carcinogenesis. We demonstrate that the endogenous AHR physically
      associates with the endogenous TRAP/DRIP/ARC/Mediator complex in a ligand
      dependent manner. The Med220 subunit, which is known to interact with several
      nuclear hormone receptors through its LXXLL motifs, potentiates AHR-dependent
      reporter gene activity in an LXXLL-independent manner. Depletion of Med220
      substantially reduces endogenous AHR-mediated transcription from the mouse
      cytochrome P4501A1 gene (CYP1A1). Both Med220 and CDK8 (another subunit of
      TRAP/DRIP/ARC/Mediator) are recruited to the CYP1A1 enhancer in a TCDD (2,3,7,8
      tetrachlorodibenzo-p-dioxin)-dependent fashion in vivo, and Med220 LXXLL motifs
      are not required. Med220 rapidly and persistently associates with the enhancer
      but not the promoter of the CYP1A1 gene after TCDD treatment with similar
      kinetics as AHR and the coactivators p300 and p/CIP. Our findings demonstrate a
      novel role for Med220 in AHR-regulated transcription that differs mechanistically
      from its role in transcriptional regulation by other previously studied
      transcription factors.

PMID- 14729674
TI  - Distinct roles for the catalytic and hemopexin domains of membrane type 1-matrix
      metalloproteinase in substrate degradation and cell migration.
AB  - Substrate degradation and cell migration are key steps in cancer metastasis.
      Membrane-type 1-matrix metalloproteinase (MT1-MMP) has been linked with these
      processes. Using the fluorescein isothiocyanate (FITC)-labeled fibronectin
      degradation assay combined with the phagokinetic cell migration assay, structure
      function relationships of MT1-MMP were studied. Our data indicate that MT1-MMP
      initiates substrate degradation and enhances cell migration; cell migration
      occurs as a concurrent but independent event. Using recombinant DNA approaches,
      we demonstrated that the hemopexin-like domain and a nonenzymatic component of
      the catalytic domain of MT1-MMP are essential for MT1-MMP-mediated cell
      migration. Because the cytoplasmic domain of MT1-MMP was not required for MT1-MMP
      mediated fibronectin degradation and cell migration, it is proposed that cross
      talk between the hemopexin domain of MT1-MMP and adjacent cell surface molecules
      is responsible for outside-in signaling. Employing cDNAs encoding dominant
      negative mutations, we demonstrated that Rac1 participates in the MT1-MMP signal
      transduction pathway. These data demonstrated that each domain of MT1-MMP plays a
      distinct role in substrate degradation and cell migration.

PMID- 14729675
TI  - Bid, but not Bax, regulates VDAC channels.
AB  - During apoptosis, cytochrome c is released from mitochondria into the cytosol,
      where it participates in caspase activation. Various and often conflicting
      mechanisms have been proposed to account for the increased permeability of the
      mitochondrial outer membrane that is responsible for this process. The voltage
      dependent anion channel (VDAC) is the major permeability pathway for metabolites
      in the mitochondrial outer membrane and therefore is a very attractive candidate
      for cytochrome c translocation. Here, we report that properties of VDAC channels
      reconstituted into planar phospholipid membranes are unaffected by addition of
      the pro-apoptotic protein Bax under a variety of conditions. Contrary to other
      reports (Shimizu, S., Narita, M., and Tsujimoto, Y. (1999) Nature 399, 483-487;
      Shimizu, S., Ide, T., Yanagida, T., and Tsujimoto, Y. (2000) J. Biol. Chem. 275,
      12321-12325; Shimizu, S., Konishi, A., Kodama, T., and Tsujimoto, Y. (2000) Proc.
      Natl. Acad. Sci. U. S. A. 97, 3100-3105), we found no electrophysiologically
      detectable interaction between VDAC channels isolated from mammalian mitochondria
      and either monomeric or oligomeric forms of Bax. We conclude that Bax does not
      induce cytochrome c release by acting on VDAC. In contrast to Bax, another pro
      apoptotic protein (Bid) proteolytically cleaved with caspase-8 affected the
      voltage gating of VDAC by inducing channel closure. We speculate that by
      decreasing the probability of VDAC opening, Bid reduces metabolite exchange
      between mitochondria and the cytosol, leading to mitochondrial dysfunction.

PMID- 14729676
TI  - Telomeric DNA damage by topoisomerase I. A possible mechanism for cell killing by
      camptothecin.
AB  - Topoisomerase I adjusts torsional stress in the genome by breaking and resealing
      one strand of the helix through a transient covalent coupling between enzyme and
      DNA. Camptothecin, a specific topoisomerase I poison, traps this covalent
      intermediate, thereby damaging the genome. Here we examined the activity of
      topoisomerase I at telomeric repeats to determine whether telomere structures are
      targets for DNA damage. We show that topoisomerase I is catalytically active in
      cleaving the G-rich telomeric strand in vitro in the presence of camptothecin but
      not in cleaving the C-rich strand. The topoisomerase I cleavage site is 5'-TT
      (downward arrow) AGGG-3' (cleavage site marked by the downward arrow). We also
      show that endogenous topoisomerase I can access telomeric DNA in vivo and form
      camptothecin-dependent covalent complexes. Therefore, each telomeric repeat
      represents a potential topoisomerase I cleavage site in vivo. Because telomere
      structures are comprised of a large number of repeats, telomeres in fact
      represent a high concentration of nested topoisomerase I sites. Therefore, more
      telomeric DNA damage by camptothecin could occur in cells with longer telomeres
      when cells possess equivalent levels of topoisomerase I. The evidence presented
      here suggests that DNA damage at telomeric repeats by topoisomerase I is a
      prominent feature of cell killing by camptothecin and triggers camptothecin
      induced apoptosis.

PMID- 14729677
TI  - Trigonal DnaK-DnaJ complex versus free DnaK and DnaJ: heat stress converts the
      former to the latter, and only the latter can do disaggregation in cooperation
      with ClpB.
AB  - DnaK from Thermus thermophilus (TDnaK) is unique because significant fractions of
      cellular TDnaK exist as a trigonal K.J complex that consists of three copies each
      of TDnaK, TDnaJ, and an assembly factor TDafA. Here, chaperone functions of the
      K.J complex and free TDnaK plus free TDnaJ (K+J) were compared. Substrate
      proteins were completely denatured at 72-73 degrees C or 89 degrees C in the
      absence or the presence of K.J complex or K+J and were subsequently incubated at
      a moderate temperature of 55 degrees C. TGrpE and ATP were always included in the
      K.J complex and K+J, and TClpB was supplemented at 55 degrees C. At 72-73 degrees
      C, both the K.J complex and K+J suppressed heat aggregation of substrate
      proteins. During the next incubation at 55 degrees C, K+J, assisted by TClpB, was
      able to disaggregate the heat aggregates and efficiently reactivate activities of
      the proteins, whereas the K.J complex was not; it reactivated only the soluble
      inactivated proteins. When substrate proteins were heated to 89 degrees C, both
      the K.J complex and K+J were no longer able to prevent heat aggregation, and
      because of selective, irreversible denaturation of TDafA the K.J complex
      dissociated into K+J, which then exhibited disaggregation activity during the
      next incubation at 55 degrees C. Thus, TClpB-assisted disaggregation activity
      belongs only to K+J, and TDafA is a potential thermosensor for converting the K.J
      complex to K+J in response to heat stress.

PMID- 14729679
TI  - Up-regulation of vascular endothelial growth factor-A by active membrane-type 1
      matrix metalloproteinase through activation of Src-tyrosine kinases.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial
      growth factor (VEGF) are two key molecules involved in pericellular proteolysis
      and cell proliferation during tumor growth and angiogenesis. Our previous data
      showed that MT1-MMP overexpression in human breast carcinoma MCF7 cells induced
      an up-regulation of VEGF expression. This effect was associated in vivo with
      accelerated tumor growth and angiogenesis. We now provide evidence that MT1-MMP
      overexpression specifically affected VEGF-A production and failed to influence
      that of other VEGF family members (VEGF, B, C, D, or PlGF) or their receptors.
      The up-regulation of VEGF-A by MT1-MMP was related to an increased
      transcriptional activation rather than to a modification of mRNA stability. It
      was blocked by synthetic MMP inhibitors, TIMP2, but not TIMP-1 and abolished by a
      partial deletion of the catalytic domain or the cytoplasmic tail of MT1-MMP.
      Analysis of the signal transduction mechanisms demonstrated that MT1-MMP acts
      through a signaling pathway involving Src tyrosine kinases. Thus, our results
      provide new insight into the mechanisms of action of MT1-MMP during angiogenesis
      and suggest that the full enzymatic activity of MT1-MMP is required for a
      specific up-regulation of VEGF-A through an activation of Src tyrosine kinase
      pathways.

PMID- 14729678
TI  - Nuclear export of the oncoprotein v-ErbA is mediated by acquisition of a viral
      nuclear export sequence.
AB  - v-ErbA, an oncogenic derivative of the thyroid hormone receptor alpha (TRalpha)
      carried by the avian erythroblastosis virus, contains several alterations
      including fusion of a portion of avian erythroblastosis virus Gag to its N
      terminus, N- and C-terminal deletions, and 13 amino acid substitutions. Nuclear
      export of v-ErbA occurs through a CRM1-mediated pathway. In contrast, nuclear
      export of TRalpha and another isoform, TRbeta, is CRM1-independent. To determine
      which amino acid changes in v-ErbA confer CRM1-dependent nuclear export, we
      expressed a panel of green and yellow fluorescent protein-tagged mutant and
      chimeric proteins in mammalian cells. The sensitivity of subcellular trafficking
      of these mutants to leptomycin B (LMB), a specific inhibitor of CRM1, was
      assessed by fluorescence microscopy. Our data showed that a nuclear export
      sequence resides within a 70-amino acid domain in the C-terminal portion of the
      p10 region of Gag, and in vitro binding assays demonstrated that Gag interacts
      directly with CRM1. However, a panel of ligand-binding domain mutants of v-ErbA
      lacking the Gag sequence exhibited greater nuclear localization in the presence
      of LMB, suggesting that the various amino acid substitutions/deletions may cause
      a conformation shift, unmasking an additional CRM1-dependent nuclear export
      sequence. In contrast, the altered DNA-binding domain of the oncoprotein did not
      contribute to CRM1-dependent nuclear export. Heterokaryon experiments revealed
      that v-ErbA did not undergo nucleocytoplasmic shuttling when the CRM1 export
      pathway was blocked by LMB treatment, suggesting that the ability to follow the
      export pathway used by TRalpha has been lost by the oncoprotein during its
      evolution. Our findings thus point to the intriguing possibility that acquisition
      of altered nuclear export capabilities contributes to the oncogenic properties of
      v-ErbA.

PMID- 14729680
TI  - Modulation of interprotomer relationships is important for activation of dimeric
      calcium-sensing receptor.
AB  - The extracellular calcium-sensing receptor (CaR) forms a disulfide-linked dimer
      through cysteine residues within its N-terminal extracellular domain (ECD).
      However, these disulfide linkages are dispensable for the formation of the
      dimeric CaR and for the functional reconstitution of two inactive CaRs. In this
      study, using molecular modeling, mutagenesis, and biochemical and biophysical
      analyses, we examined the importance of two leucine residues, Leu-112 and Leu
      156, in the ECD of the CaR for the non-covalent dimerization and functional
      reconstitution. We found that the mutant receptor carrying L112S and L156S still
      exists mostly as a covalently linked dimer and has a significantly higher
      apparent affinity for calcium than the wild-type receptor. However, a combination
      of four mutations, L112S, L156S, C129S, and C131S, significantly reduces receptor
      dimerization and markedly inactivates the CaR. We also found that L112S and L156S
      mediate the non-covalent intermolecular interactions important for functional
      reconstitution. Because mutating either the two cysteines or the two leucines
      enhances the apparent ligand affinity of the CaR, it is likely that the changes
      in intermolecular relationships between two receptor protomers linked by these
      leucines and cysteines are essential for receptor activation. Moreover, these
      mutations are unlikely to have negative effects on the secondary structure of
      each protomer of the dimeric receptor. Thus, the detrimental effects of the
      combined mutations on the function of the CaR further suggest that CaR
      dimerization through its ECD is essential for the formation of a functional
      tertiary structure of the CaR.

PMID- 14729681
TI  - Infection-induced up-regulation of the costimulatory molecule 4-1BB in
      osteoblastic cells and its inhibitory effect on M-CSF/RANKL-induced in vitro
      osteoclastogenesis.
AB  - Bacterial infection sometimes impairs bone metabolism. In this study, we infected
      the osteoblastic cell line MC3T3-E1 with Mycobacterium bovis bacillus Calmette
      Guerin (BCG) and identified genes that were up-regulated in the BCG-infected
      cells by the suppression subtractive hybridization method. A gene encoding 4-1BB
      (CD137), a member of the tumor necrosis factor-alpha receptor family, was found
      to be one of the up-regulated genes. Up-regulation of 4-1BB was also observed by
      infection with Escherichia coli, Salmonella typhimurium, and Staphylococcus
      aureus, and by treatment with lipopolysaccharides and heat-killed BCG. Bone
      marrow cells and the macrophage-like cell lines J774 and RAW264.7 were found to
      express 4-1BB ligand (4-1BBL). Recombinant 4-1BB (r4-1BB) that was immobilized on
      culture plates strongly inhibited macrophage colony stimulating factor (M
      CSF)/receptor activator of nuclear factor-kappaB ligand (RANKL)-induced in vitro
      osteoclast formation from bone marrow cells. Anti-4-1BBL antibody also inhibited
      osteoclast formation to a lesser extent, indicating involvement of reverse
      signaling through 4-1BBL during inhibition of osteoclast formation. A casein
      kinase I (CKI) inhibitor markedly suppressed the inhibitory effect of r4-1BB on M
      CSF/RANKL-induced osteoclast formation, suggesting that CKI might be involved in
      4-1BB/4-1BBL reverse signaling. r4-1BB showed no effects on M-CSF- or RANKL
      induced phosphorylation of I-kappaB, ERK1/2, p38, or JNK, whereas RANKL-induced
      phosphorylation of Akt, a downstream target of phosphatidylinositol 3-kinase
      (PI3K), was completely abolished by r4-1BB, suggesting that 4-1BB/4-1BBL reverse
      signaling may interfere with PI3K/Akt pathway. r4-1BB also abolished RANKL
      mediated induction of nuclear factor of activated T cells-2. This study may
      elucidate a novel role of 4-1BB in cell metabolism, especially
      osteoclastogenesis.

PMID- 14729682
TI  - Gating effects of mutations in the Cav3.2 T-type calcium channel associated with
      childhood absence epilepsy.
AB  - Childhood absence epilepsy (CAE) is a type of generalized epilepsy observed in 2
      10% of epileptic children. In a recent study by Chen et al. (Chen, Y., Lu, J.,
      Pan, H., Zhang, Y., Wu, H., Xu, K., Liu, X., Jiang, Y., Bao, X., Yao, Z., Ding,
      K., Lo, W. H., Qiang, B., Chan, P., Shen, Y., and Wu, X. (2003) Ann. Neurol. 54,
      239-243) 12 missense mutations were identified in the CACNA1H (Ca(v)3.2) gene in
      14 of 118 patients with CAE but not in 230 control individuals. We have
      functionally characterized five of these mutations (F161L, E282K, C456S, V831M,
      and D1463N) using rat Ca(v)3.2 and whole-cell patch clamp recordings in
      transfected HEK293 cells. Two of the mutations, F161L and E282K, mediated an
      approximately 10-mV hyperpolarizing shift in the half-activation potential.
      Mutation V831M caused a approximately 50% slowing of inactivation relative to
      control and shifted half-inactivation potential approximately 10 mV toward more
      depolarized potentials. Mean time to peak was significantly increased by mutation
      V831M but was unchanged for all others. No resolvable changes in the parameters
      of the IV relation or current kinetics were observed with the remaining
      mutations. The findings suggest that several of the Ca(v)3.2 mutants allow for
      greater calcium influx during physiological activation and in the case of F161L
      and E282K can result in channel openings at more hyperpolarized (close to
      resting) potentials. This may underlie the propensity for seizures in patients
      with CAE.

PMID- 14729683
TI  - Lysogeny at mid-twentieth century: P1, P2, and other experimental systems.

PMID- 14729685
TI  - In vivo expression of the mannose-resistant fimbriae of Photorhabdus temperata
      K122 during insect infection.
AB  - Photorhabdus temperata K122 is an entomopathogenic bacterium symbiotically
      associated with nematodes of the family Heterorhabditidae: Surface fimbriae are
      important for the colonization of many pathogenic bacteria, and here we report
      the nucleotide sequence and analysis of the expression of a 12-kbp fragment
      encoding the mannose-resistant fimbriae of P. temperata (mrf). The mrf gene
      cluster contains 11 genes with an organization similar to that of the mrp locus
      from Proteus mirabilis. mrfI (encoding a putative recombinase) and mrfA (encoding
      pilin), the first gene in an apparent operon of nine other genes, are expressed
      from divergent promoters. The mrfI-mrfA intergenic region contains inverted
      repeats flanking the mrfA promoter. This region was shown to be capable of
      inversion, consistent with an ON/OFF regulation of the operon. In in vitro liquid
      cultures, both orientations were detected. Nevertheless, when we analyzed the
      expression of all of the genes in the mrf locus by semiquantitative reverse
      transcription-PCR during infection of Galleria mellonella (greater wax moth)
      larvae, expression of mrfA was not detected until 25 h postinfection, preceding
      the death of the larvae at 32 h. In contrast, mrfJ (a putative inhibitor of
      flagellar synthesis) was expressed throughout infection. Expression of mrfI was
      also detected only late in infection (25 to 30 h), indicating a possible increase
      in inversion frequency at this stage. In both in vitro liquid cultures and in
      vivo larval infections, the distal genes of the operon were expressed at
      substantially lower levels than mrfA. These results indicate the complex
      regulation of the mrf cluster during infection.

PMID- 14729684
TI  - The NifL-NifA System: a multidomain transcriptional regulatory complex that
      integrates environmental signals.

PMID- 14729686
TI  - A novel evolutionary lineage of carbonic anhydrase (epsilon class) is a component
      of the carboxysome shell.
AB  - A significant portion of the total carbon fixed in the biosphere is attributed to
      the autotrophic metabolism of prokaryotes. In cyanobacteria and many
      chemolithoautotrophic bacteria, CO(2) fixation is catalyzed by ribulose-1,5
      bisphosphate carboxylase/oxygenase (RuBisCO), most if not all of which is
      packaged in protein microcompartments called carboxysomes. These structures play
      an integral role in a cellular CO(2)-concentrating mechanism and are essential
      components for autotrophic growth. Here we report that the carboxysomal shell
      protein, CsoS3, from Halothiobacillus neapolitanus is a novel carbonic anhydrase
      (epsilon-class CA) that has an evolutionary lineage distinct from those
      previously recognized in animals, plants, and other prokaryotes. Functional CAs
      encoded by csoS3 homologues were also identified in the cyanobacteria
      Prochlorococcus sp. and Synechococcus sp., which dominate the oligotrophic oceans
      and are major contributors to primary productivity. The location of the
      carboxysomal CA in the shell suggests that it could supply the active sites of
      RuBisCO in the carboxysome with the high concentrations of CO(2) necessary for
      optimal RuBisCO activity and efficient carbon fixation in these prokaryotes,
      which are important contributors to the global carbon cycle.

PMID- 14729687
TI  - Reversible acyl-homoserine lactone binding to purified Vibrio fischeri LuxR
      protein.
AB  - The Vibrio fischeri LuxR protein is the founding member of a family of acyl
      homoserine lactone-responsive quorum-sensing transcription factors. Previous
      genetic evidence indicates that in the presence of its quorum-sensing signal, N
      (3-oxohexanoyl) homoserine lactone (3OC6-HSL), LuxR binds to lux box DNA within
      the promoter region of the luxI gene and activates transcription of the
      luxICDABEG luminescence operon. We have purified LuxR from recombinant
      Escherichia coli. Purified LuxR binds specifically and with high affinity to DNA
      containing a lux box. This binding requires addition of 3OC6-HSL to the assay
      reactions, presumably forming a LuxR-3OC6-HSL complex. When bound to the lux box
      at the luxI promoter in vitro, LuxR-3OC6-HSL enables E. coli RNA polymerase to
      initiate transcription from the luxI promoter. Unlike the well-characterized LuxR
      homolog TraR in complex with its signal (3-oxo-octanoyl-HSL), the LuxR-30C6-HSL
      complex can be reversibly inactivated by dilution, suggesting that 3OC6-HSL in
      the complex is not tightly bound and is in equilibrium with the bulk solvent.
      Thus, although LuxR and TraR both bind 3-oxoacyl-HSLs, the binding is
      qualitatively different. The differences have implications for the ways in which
      these proteins respond to decreases in signal concentrations or rapid drops in
      population density.

PMID- 14729688
TI  - The Streptococcus gordonii platelet binding protein GspB undergoes glycosylation
      independently of export.
AB  - The binding of bacteria and platelets may play a central role in the pathogenesis
      of infective endocarditis. Platelet binding by Streptococcus gordonii strain M99
      is predominantly mediated by the 286-kDa cell wall-anchored protein GspB. This
      unusually large protein lacks a typical amino-terminal signal peptide and is
      translocated from the cytoplasm via a dedicated transport system. A 14-kb segment
      just downstream of gspB encodes SecA2 and SecY2, two components of the GspB
      specific transport system. The downstream segment also encodes several putative
      glycosyl transferases that may be responsible for the posttranslational
      modification of GspB. In this study, we compared the abilities of M99 and two
      GspB(-) mutant strains to bind various lectins. GspB was found to have affinity
      for lectins that bind N-acetylglucosamine. We also examined variant forms of GspB
      that lack a carboxy-terminal cell wall-anchoring domain and thus are free of
      covalent linkage to cell wall peptidoglycan. Like native GspB, these truncated
      proteins appear to be heavily glycosylated, as evidenced by migration during
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent
      molecular mass >100 kDa in excess of the predicted mass, negligible staining with
      conventional protein stains, and reactivity with hydrazide following periodate
      oxidation. Furthermore, analysis of the carbohydrate associated with the GspB
      variants by high-pH anion-exchange chromatography revealed the presence of
      approximately 70 to 100 monosaccharide residues per GspB polypeptide (primarily N
      acetylglucosamine and glucose). Analysis of GspB in protoplasts of secA2 or secY2
      mutant strains, which do not export GspB, indicates that GspB is glycosylated in
      the cytoplasm of these strains. The combined data suggest that the native GspB is
      a glycoprotein and that it may be glycosylated prior to export.

PMID- 14729689
TI  - Nine mutants of Chlorobium tepidum each unable to synthesize a different
      chlorosome protein still assemble functional chlorosomes.
AB  - Chlorosomes of the green sulfur bacterium Chlorobium tepidum comprise mostly
      bacteriochlorophyll c (BChl c), small amounts of BChl a, carotenoids, and
      quinones surrounded by a lipid-protein envelope. These structures contain 10
      different protein species (CsmA, CsmB, CsmC, CsmD, CsmE, CsmF, CsmH, CsmI, CsmJ,
      and CsmX) but contain relatively little total protein compared to other
      photosynthetic antenna complexes. Except for CsmA, which has been suggested to
      bind BChl a, the functions of the chlorosome proteins are not known. Nine mutants
      in which a single csm gene was inactivated were created; these mutants included
      genes encoding all chlorosome proteins except CsmA. All mutants had BChl c
      contents similar to that of the wild-type strain and had growth rates
      indistinguishable from or within approximately 90% (CsmC(-) and CsmJ(-)) of those
      of the wild-type strain. Chlorosomes isolated from the mutants lacked only the
      protein whose gene had been inactivated and were generally similar to those from
      the wild-type strain with respect to size, shape, and BChl c, BChl a, and
      carotenoid contents. However, chlorosomes from the csmC mutant were about 25%
      shorter than those from the wild-type strain, and the BChl c absorbance maximum
      was blue-shifted about 8 nm, indicating that the structure of the BChl c
      aggregates in these chlorosomes is altered. The results of the present study
      establish that, except with CsmA, when the known chlorosome proteins are
      eliminated individually, none of them are essential for the biogenesis, light
      harvesting, or structural organization of BChl c and BChl a within the
      chlorosome. These results demonstrate that chlorosomes are remarkably robust
      structures that can tolerate considerable changes in protein composition.

PMID- 14729690
TI  - Genetic analysis of disulfide isomerization in Escherichia coli: expression of
      DsbC is modulated by RNase E-dependent mRNA processing.
AB  - We designed a selection strategy for the isolation of Escherichia coli mutants
      exhibiting enhanced protein disulfide isomerase activity. The folding of a
      variant of tissue plasminogen activator (v-tPA), a protein containing nine
      disulfide bonds, in the bacterial periplasm is completely dependent on the level
      of disulfide isomerase activity of the cell. Mutations that increase this
      activity mediate the formation of catalytically active v-tPA, which in turn
      cleaves a p-aminobenzoic acid (PABA)-peptide adduct to release free PABA and thus
      allows the growth of an auxotrophic strain. Following chemical mutagenesis, a
      total of eight E. coli mutants exhibiting significantly higher disulfide
      isomerization activity, not only with v-tPA but also with two other unrelated
      protein substrates, were isolated. This phenotype resulted from significantly
      increased expression of the bacterial disulfide isomerase DsbC. In seven of the
      eight mutants, the upregulation of DsbC was found to be related to defects in RNA
      processing by RNase E, the rne gene product. Specifically, the genetic lesions in
      five mutants were shown to be allelic to rne, while an additional two mutants
      exhibited impaired RNase E activity due to lesions in other loci. The importance
      of mRNA stability on the expression of DsbC is underscored by the short half-life
      of the dsbC transcript, which was found to be only 0.8 min at 37 degrees C in
      wild-type cells but was two- to threefold longer in some of the stronger mutants.
      These results (i) confirm the central role of DsbC in disulfide bond
      isomerization in the bacterial periplasm and (ii) suggest a critical role for
      RNase E in regulating DsbC expression.

PMID- 14729691
TI  - Mutational analysis of the Myxococcus xanthus Omega4400 promoter region provides
      insight into developmental gene regulation by C signaling.
AB  - Myxococcus xanthus utilizes extracellular signals during development to
      coordinate cell movement, differentiation, and changes in gene expression. One of
      these signals, the C signal, regulates the expression of many genes, including
      Omega4400, a gene identified by an insertion of Tn5 lac into the chromosome.
      Expression of Tn5 lac Omega4400 is reduced in csgA mutant cells, which fail to
      perform C signaling, and the promoter region has several sequences similar to
      sequences found in the regulatory regions of other C-signal-dependent genes. One
      such gene, Omega4403, depends absolutely on the C signal for expression, and its
      promoter region has been characterized previously by mutational analysis. To
      determine if the similar sequences within the Omega4400 and Omega4403 regulatory
      regions function in the same way, deletion analysis and site-directed mutagenesis
      of the Omega4400 promoter region were performed. A 7-bp sequence centered at -49
      bp, termed a C box, is identical in the Omega4400 and Omega4403 promoter regions,
      yet mutations in the individual base pairs affected expression from the two
      promoters very differently. Also, a single-base-pair change within a similar 5-bp
      element, which is centered at -61 bp in both promoter regions, had very different
      effects on the activities of the two promoters. Further mutational analysis
      showed that two regions are important for Omega4400 expression; one region, from 
      63 to -31 bp, is required for Omega4400 expression, and the other, from -86 to 
      81 bp, exerts a two- to fourfold effect on expression and is at least partially
      responsible for the C signal dependence of the Omega4400 promoter. Mutations in
      sigD and sigE, which are genes that encode sigma factors, abolished and reduced
      Omega4400 expression, respectively. Expression of Omega4400 in actB or actC
      mutants correlated well with the altered levels of C signal produced in these
      mutants. Our results provide the first detailed analysis of an M. xanthus
      regulatory region that depends partially on C signaling for expression and
      indicate that similar DNA sequences in the Omega4400 and Omega4403 promoter
      regions function differently.

PMID- 14729692
TI  - A novel putative enterococcal pathogenicity island linked to the esp virulence
      gene of Enterococcus faecium and associated with epidemicity.
AB  - Enterococcus faecalis harbors a virulence-associated surface protein encoded by
      the esp gene. This gene has been shown to be part of a 150-kb putative
      pathogenicity island. A gene similar to esp has recently been found in
      Enterococcus faecium isolates recovered from hospitalized patients. In the
      present study we analyzed the polymorphism in the esp gene of E. faecium, and we
      investigated the association of esp with neighboring chromosomal genes. The esp
      gene showed considerable sequence heterogeneity in the regions encoding the
      nonrepeat N- and C-terminal domains of the Esp protein as well as differences in
      the number of repeats. DNA sequencing of chromosomal regions flanking the esp
      gene of E. faecium revealed seven open reading frames, representing putative
      genes implicated in virulence, regulation of transcription, and antibiotic
      resistance. These flanking regions were invariably associated with the presence
      or absence of the esp gene in E. faecium, indicating that esp in E. faecium is
      part of a distinct genetic element. Because of the presence of virulence genes in
      this gene cluster, the lower G+C content relative to that of the genome, and the
      presence of esp in E. faecium isolates associated with nosocomial outbreaks and
      clinically documented infections, we conclude that this genetic element
      constitutes a putative pathogenicity island, the first one described in E.
      faecium. Except for the presence of esp and araC, this pathogenicity island is
      completely different from the esp-containing pathogenicity island previously
      disclosed in E. faecalis.

PMID- 14729693
TI  - ATP/ADP translocases: a common feature of obligate intracellular amoebal
      symbionts related to Chlamydiae and Rickettsiae.
AB  - ATP/ADP translocases catalyze the highly specific transport of ATP across a
      membrane in an exchange mode with ADP. Such unique transport proteins are
      employed by plant plastids and have among the prokaryotes so far only been
      identified in few obligate intracellular bacteria belonging to the Chlamydiales
      and the Rickettsiales. In this study, 12 phylogenetically diverse bacterial
      endosymbionts of free-living amoebae and paramecia were screened for the presence
      of genes encoding ATP/ADP transport proteins. The occurrence of ATP/ADP
      translocase genes was found to be restricted to endosymbionts related to
      rickettsiae and chlamydiae. We showed that the ATP/ADP transport protein of the
      Parachlamydia-related endosymbiont of Acanthamoeba sp. strain UWE25, a recently
      identified relative of the important human pathogens Chlamydia trachomatis and
      Chlamydophila pneumoniae, is functional when expressed in the heterologous host
      Escherichia coli and demonstrated the presence of transcripts during the
      chlamydial developmental cycle. These findings indicate that the interaction
      between Parachlamydia-related endosymbionts and their amoeba hosts concerns
      energy parasitism similar to the interaction between pathogenic chlamydiae and
      their human host cells. Phylogenetic analysis of all known ATP/ADP translocases
      indicated that the genes encoding ATP/ADP translocases originated from a
      chlamydial ancestor and were, after an ancient gene duplication, transferred
      horizontally to rickettsiae and plants.

PMID- 14729694
TI  - Quorum sensing-controlled biofilm development in Serratia liquefaciens MG1.
AB  - Serratia liquefaciens MG1 contains an N-acylhomoserine lactone-mediated quorum
      sensing system that is known to regulate swarming motility colonization. In this
      study, we describe for S. liquefaciens MG1 the development of a novel biofilm
      consisting of cell aggregates and differentiated cell types, such as cell chains
      and long filamentous cells. Furthermore, quorum sensing is shown to be crucial
      for normal biofilm development and for elaborate differentiation. A mutant of S.
      liquefaciens MG1 that was incapable of synthesizing extracellular signal formed a
      thin and nonmature biofilm lacking cell aggregates and differentiated cell
      chains. Signal-based complementation of this mutant resulted in a biofilm with
      the wild-type architecture. Two quorum-sensing-regulated genes (bsmA and bsmB)
      involved in biofilm development were identified, and we propose that these genes
      are engaged in fine-tuning the formation of cell aggregates at a specific point
      in biofilm development.

PMID- 14729695
TI  - Regulation of IcsP, the outer membrane protease of the Shigella actin tail
      assembly protein IcsA, by virulence plasmid regulators VirF and VirB.
AB  - The Shigella outer membrane protease IcsP removes the actin assembly protein IcsA
      from the bacterial surface, and consequently modulates Shigella actin-based
      motility and cell-to-cell spread. Here, we demonstrate that IcsP expression is
      undetectable in mutants lacking either of two transcriptional activators, VirF
      and VirB. In wild-type Shigella spp., virB expression is entirely dependent on
      VirF; therefore, to circumvent this regulatory cascade, we independently
      expressed VirF or VirB in Shigella strains lacking both activators and measured
      both IcsP levels and transcription from the icsP promoter. Our results show that
      VirB significantly enhanced icsP transcription, even in the absence of VirF. In
      contrast, when VirF was induced in the absence of VirB, VirF had variable
      effects. The regulation of icsP is distinctly different from the regulation of
      the gene encoding its major substrate, icsA, which is activated by VirF and not
      VirB. We propose that the different pathways regulating icsA and icsP may be
      critical to the modulation of IcsA-mediated actin-based motility by IcsP.

PMID- 14729696
TI  - The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase.
AB  - The K1 capsule is an essential virulence determinant of Escherichia coli strains
      that cause meningitis in neonates. Biosynthesis and transport of the capsule, an
      alpha-2,8-linked polymer of sialic acid, are encoded by the 17-kb kps gene
      cluster. We deleted neuC, a K1 gene implicated in sialic acid synthesis, from the
      chromosome of EV36, a K-12-K1 hybrid, by allelic exchange. Exogenously added
      sialic acid restored capsule expression to the deletion strain (DeltaneuC),
      confirming that NeuC is necessary for sialic acid synthesis. The deduced amino
      acid sequence of NeuC showed similarities to those of UDP-N-acetylglucosamine
      (GlcNAc) 2-epimerases from both prokaryotes and eukaryotes. The NeuC homologue
      from serotype III Streptococcus agalactiae complements DeltaneuC. We cloned the
      neuC gene into an intein expression vector to facilitate purification. We
      demonstrated by paper chromatography that the purified neuC gene product
      catalyzed the formation of [2-(14)C]acetamidoglucal and [N
      (14)C]acetylmannosamine (ManNAc) from UDP-[(14)C]GlcNAc. The formation of
      reaction intermediate 2-acetamidoglucal with the concomitant release of UDP was
      confirmed by proton and phosphorus nuclear magnetic resonance spectroscopy. NeuC
      could not use GlcNAc as a substrate. These data suggest that neuC encodes an
      epimerase that catalyzes the formation of ManNAc from UDP-GlcNAc via a 2
      acetamidoglucal intermediate. The unexpected release of the glucal intermediate
      and the extremely low rate of ManNAc formation likely were a result of the in
      vitro assay conditions, in which a key regulatory molecule or protein was absent.

PMID- 14729697
TI  - The Lactococcal abortive phage infection system AbiP prevents both phage DNA
      replication and temporal transcription switch.
AB  - We describe here a new lactococcal abortive phage infection system, designated
      AbiP. AbiP is effective against some lactococcal phages of one prevalent group,
      936, but not against phages from the other two groups (c6A and P335). It was
      identified in the Lactococcus lactis subsp. cremoris strain IL420, on the native
      plasmid pIL2614. AbiP is encoded by a single gene, expressed in an operon with a
      second gene. In this work, abiP is shown to affect both the replication and
      transcription of phage DNA. In AbiP(+) cells, phage DNA replication is arrested
      approximately 10 min after infection. Levels of middle and late phage transcripts
      are lower in AbiP(+) than in AbiP(-) cells, probably due to the smaller amount of
      phage DNA. By contrast, early phage transcripts are more abundant in AbiP(+) than
      in AbiP(-) cells, suggesting that the switch-off, which occurs 15 min after
      infection in AbiP(-) cells, is prevented in AbiP(+) cells.

PMID- 14729698
TI  - Control of glucose- and NaCl-induced biofilm formation by rbf in Staphylococcus
      aureus.
AB  - Both Staphylococcus aureus and S. epidermidis are capable of forming biofilm on
      biomaterials. We used Tn917 mutagenesis to identify a gene, rbf, affecting
      biofilm formation in S. aureus NCTC8325-4. Sequencing revealed that Rbf contained
      a consensus region signature of the AraC/XylS family of regulators, suggesting
      that Rbf is a transcriptional regulator. Insertional duplication inactivation of
      the rbf gene confirmed that the gene was involved in biofilm formation on
      polystyrene and glass. Phenotypic analysis of the wild type and the mutant
      suggested that the rbf gene mediates the biofilm formation of S. aureus at the
      multicellular aggregation stage rather than at initial attachment. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis demonstrated that the
      mutation resulted in the loss of an approximately 190-kDa protein. Biofilm
      production by the mutant could be restored by complementation with a 2.5-kb DNA
      fragment containing the rbf gene. The rbf-specific mutation affected the
      induction of biofilm formation by glucose and a high concentration of NaCl but
      not by ethanol. The mutation did not affect the transcription of the ica genes
      previously shown to be required for biofilm formation. Taken together, our
      results suggest that the rbf gene is involved in the regulation of the
      multicellular aggregation step of S. aureus biofilm formation in response to
      glucose and salt and that this regulation may be mediated through the 190-kDa
      protein.

PMID- 14729699
TI  - A mutant form of the Neisseria gonorrhoeae pilus secretin protein PilQ allows
      increased entry of heme and antimicrobial compounds.
AB  - A spontaneous point mutation in pilQ (pilQ1) resulted in phenotypic suppression
      of a hemoglobin (Hb) receptor mutant (hpuAB mutant), allowing gonococci to grow
      on Hb as the sole source of iron. PilQ, formerly designated OMP-MC, is a member
      of the secretin family of proteins located in the outer membrane and is required
      for pilus biogenesis. The pilQ1 mutant also showed decreased piliation and
      transformation efficiency. Insertional inactivation of pilQ1 resulted in the loss
      of the Hb utilization phenotype and decreased entry of free heme. Despite the
      ability of the pilQ1 mutant to use Hb for iron acquisition and porphyrin, there
      was no demonstrable binding of Hb to the cell surface. The pilQ1 mutant was more
      sensitive to the toxic effect of free heme in growth medium and hypersensitive to
      the detergent Triton X-100 and multiple antibiotics. Double mutation in pilQ1 and
      tonB had no effect on these phenotypes, but a double pilQ1 pilT mutant showed a
      reduction in Hb-dependent growth and decreased sensitivity to heme and various
      antimicrobial agents. Insertional inactivation of wild-type pilQ also resulted in
      reduced entry of heme, Triton X-100, and some antibiotics. These results show
      that PilQ forms a channel that allows entry of heme and certain antimicrobial
      compounds and that a gain-of function point mutation in pilQ results in TonB
      independent, PilT-dependent increase of entry.

PMID- 14729700
TI  - Rhodobacter capsulatus nifA1 promoter: high-GC -10 regions in high-GC bacteria
      and the basis for their transcription.
AB  - It was previously shown that the Rhodobacter capsulatus NtrC enhancer-binding
      protein activates the R. capsulatus housekeeping RNA polymerase but not the
      Escherichia coli RNA polymerase at the nifA1 promoter. We have tested the
      hypothesis that this activity is due to the high G+C content of the -10 sequence.
      A comparative analysis of R. capsulatus and other alpha-proteobacterial promoters
      with known transcription start sites suggests that the G+C content of the -10
      region is higher than that for E. coli. Both in vivo and in vitro results
      obtained with nifA1 promoters with -10 and/or -35 variations are reported here. A
      major conclusion of this study is that alpha-proteobacteria have evolved a
      promiscuous sigma factor and core RNA polymerase that can transcribe promoters
      with high-GC -10 regions in addition to the classic E. coli Pribnow box. To
      facilitate studies of R. capsulatus transcription, we cloned and overexpressed
      all of the RNA polymerase subunits in E. coli, and these were reconstituted in
      vitro to form an active, recombinant R. capsulatus RNA polymerase with properties
      mimicking those of the natural polymerase. Thus, no additional factors from R.
      capsulatus are necessary for the recognition of high-GC promoters or for
      activation by R. capsulatus NtrC. The addition of R. capsulatus sigma(70) to the
      E. coli core RNA polymerase or the use of -10 promoter mutants did not facilitate
      R. capsulatus NtrC activation of the nifA1 promoter by the E. coli RNA
      polymerase. Thus, an additional barrier to activation by R. capsulatus NtrC
      exists, probably a lack of the proper R. capsulatus NtrC-E. coli RNA polymerase
      (protein-protein) interaction(s).

PMID- 14729701
TI  - The conserved Cys-X1-X2-Cys motif present in the TtcA protein is required for the
      thiolation of cytidine in position 32 of tRNA from Salmonella enterica serovar
      Typhimurium.
AB  - The modified nucleoside 2-thiocytidine (s(2)C) has so far been found in tRNA from
      organisms belonging to the phylogenetic domains Archaea and Bacteria. In the
      bacteria Escherichia coli and Salmonella enterica serovar Typhimurium, s(2)C is
      present in position 32 of only four tRNA species-, and. An in-frame deletion of
      an S. enterica gene (designated ttcA, for "two-thio-cytidine") was constructed,
      and such a mutant has no detectable s(2)C in its tRNA. The TtcA protein family is
      characterized by the existence of both a PP-loop and a Cys-X(1)-X(2)-Cys motif in
      the central region of the protein but can be divided into two distinct groups
      based on the presence and location of additional Cys-X(1)-X(2)-Cys motifs in
      terminal regions of the sequence. Mutant analysis showed that both cysteines in
      this central conserved Cys-X(1)-X(2)-Cys motif are required for the formation of
      s(2)C. The DeltattcA1 mutant grows at the same rate as the congenic wild-type
      strain, and no growth disadvantage caused by the lack of s(2)C was observed in a
      mixed-population experiment. Lack of s(2)C32 did not reduce the selection rate at
      the ribosomal aminoacyl-tRNA site (A-site) for at any of its cognate CGN codons,
      whereas A-site selection at AGG by was dependent on the presence of s(2)C32. The
      presence of s(2)C32 in peptidyl- or in peptidyl- interfered with decoding in the
      A-site. The presence of s(2)C32 in decreased the rate of translation of the CGA
      codon but not that of the CGU codon.

PMID- 14729702
TI  - Formation of thiolated nucleosides present in tRNA from Salmonella enterica
      serovar Typhimurium occurs in two principally distinct pathways.
AB  - tRNA from Salmonella enterica serovar Typhimurium contains five thiolated
      nucleosides, 2-thiocytidine (s(2)C), 4-thiouridine (s(4)U), 5-methylaminomethyl-2
      thiouridine (mnm(5)s(2)U), 5-carboxymethylaminomethyl-2-thiouridine
      (cmnm(5)s(2)U), and N-6-(4-hydroxyisopentenyl)-2-methylthioadenosine
      (ms(2)io(6)A). The levels of all of them are significantly reduced in cells with
      a mutated iscS gene, which encodes the cysteine desulfurase IscS, a member of the
      ISC machinery that is responsible for [Fe-S] cluster formation in proteins. A
      mutant (iscU52) was isolated that carried an amino acid substitution (S107T) in
      the IscU protein, which functions as a major scaffold in the formation of [Fe-S]
      clusters. In contrast to the iscS mutant, the iscU52 mutant showed reduced levels
      of only two of the thiolated nucleosides, ms(2)io(6)A (10-fold) and s(2)C (more
      than 2-fold). Deletions of the iscU, hscA, or fdx genes from the isc operon lead
      to a similar tRNA thiolation pattern to that seen for the iscU52 mutant.
      Unexpectedly, deletion of the iscA gene, coding for an alternative scaffold
      protein for the [Fe-S] clusters, showed a novel tRNA thiolation pattern, where
      the synthesis of only one thiolated nucleoside, ms(2)io(6)A, was decreased
      twofold. Based on our results, we suggest two principal distinct routes for
      thiolation of tRNA: (i) a direct sulfur transfer from IscS to the tRNA modifying
      enzymes ThiI and MnmA, which form s(4)U and the s(2)U moiety of (c)mnm(5)s(2)U,
      respectively; and (ii) an involvement of [Fe-S] proteins (an unidentified enzyme
      in the synthesis of s(2)C and MiaB in the synthesis of ms(2)io(6)A) in the
      transfer of sulfur to the tRNA.

PMID- 14729703
TI  - Direct glutaminyl-tRNA biosynthesis and indirect asparaginyl-tRNA biosynthesis in
      Pseudomonas aeruginosa PAO1.
AB  - The genomic sequence of Pseudomonas aeruginosa PAO1 was searched for the presence
      of open reading frames (ORFs) encoding enzymes potentially involved in the
      formation of Gln-tRNA and of Asn-tRNA. We found ORFs similar to known glutamyl
      tRNA synthetases (GluRS), glutaminyl-tRNA synthetases (GlnRS), aspartyl-tRNA
      synthetases (AspRS), and trimeric tRNA-dependent amidotransferases (AdT) but none
      similar to known asparaginyl-tRNA synthetases (AsnRS). The absence of AsnRS was
      confirmed by biochemical tests with crude and fractionated extracts of P.
      aeruginosa PAO1, with the homologous tRNA as the substrate. The characterization
      of GluRS, AspRS, and AdT overproduced from their cloned genes in P. aeruginosa
      and purified to homogeneity revealed that GluRS is discriminating in the sense
      that it does not glutamylate tRNA(Gln), that AspRS is nondiscriminating, and that
      its Asp-tRNA(Asn) product is transamidated by AdT. On the other hand, tRNA(Gln)
      is directly glutaminylated by GlnRS. These results show that P. aeruginosa PAO1
      is the first organism known to synthesize Asn-tRNA via the indirect pathway and
      to synthesize Gln-tRNA via the direct pathway. The essential role of AdT in the
      formation of Asn-tRNA in P. aeruginosa and the absence of a similar activity in
      the cytoplasm of eukaryotic cells identifies AdT as a potential target for
      antibiotics to be designed against this human pathogen. Such novel antibiotics
      could be active against other multidrug-resistant gram-negative pathogens such as
      Burkholderia and Neisseria as well as all pathogenic gram-positive bacteria.

PMID- 14729704
TI  - The RecA protein of Helicobacter pylori requires a posttranslational modification
      for full activity.
AB  - The RecA protein is a central component of the homologous recombination machinery
      and of the SOS system in most bacteria. In performing these functions, it is
      involved in DNA repair processes and plays an important role in natural
      transformation competence. This may be especially important in Helicobacter
      pylori, where an unusually high degree of microdiversity among strains is
      generated by homologous recombination. We have suggested previously that the H.
      pylori RecA protein is subject to posttranslational modifications that result in
      a slight shift in its electrophoretic mobility. Here we show that at least two
      genes downstream of recA are involved in this modification and that this process
      is dependent on genes involved in glycosylation and lipopolysaccharide
      biosynthesis. Site-directed mutagenesis of a putative glycosylation site results
      in production of an unmodified RecA protein. This posttranslational modification
      is not involved in membrane targeting or cell division functions but is necessary
      for the full function of RecA in DNA repair. Thus, it might be an adaptation to
      the specific requirements of H. pylori in its natural environment.

PMID- 14729705
TI  - A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia
      coli.
AB  - FtsE and FtsX have homology to the ABC transporter superfamily of proteins and
      appear to be widely conserved among bacteria. Early work implicated FtsEX in cell
      division in Escherichia coli, but this was subsequently challenged, in part
      because the division defects in ftsEX mutants are often salt remedial. Strain
      RG60 has an ftsE::kan null mutation that is polar onto ftsX. RG60 is mildly
      filamentous when grown in standard Luria-Bertani medium (LB), which contains 1%
      NaCl, but upon shift to LB with no NaCl growth and division stop. We found that
      FtsN localizes to potential division sites, albeit poorly, in RG60 grown in LB
      with 1% NaCl. We also found that in wild-type E. coli both FtsE and FtsX localize
      to the division site. Localization of FtsX was studied in detail and appeared to
      require FtsZ, FtsA, and ZipA, but not the downstream division proteins FtsK,
      FtsQ, FtsL, and FtsI. Consistent with this, in media lacking salt, FtsA and ZipA
      localized independently of FtsEX, but the downstream proteins did not. Finally,
      in the absence of salt, cells depleted of FtsEX stopped dividing before any
      change in growth rate (mass increase) was apparent. We conclude that FtsEX
      participates directly in the process of cell division and is important for
      assembly or stability of the septal ring, especially in salt-free media.

PMID- 14729706
TI  - Regulation of transcription of compatible solute transporters by the general
      stress sigma factor, sigmaB, in Listeria monocytogenes.
AB  - Listeria monocytogenes is well known for its durable physiological
      characteristics, which allow the organism to grow at low temperature and pH and
      high osmolarity. Growth under high osmolarity depends on the accumulation of
      compatible solutes, among which glycine betaine and carnitine are the preferred
      solutes for this organism. Three different transport systems, Gbu, BetL, and
      OpuC, have been identified in L. monocytogenes which serve to scavenge the
      preferred compatible solutes. The general stress response regulator sigma(B) has
      been shown to play an important role in osmotic adaptation in L. monocytogenes,
      presumably by directing transcription from one or more of the solute transport
      genes. In the studies presented here, we have used primer extension analyses to
      identify the promoter elements responsible for transcription of the opuC, gbuA,
      and betL genes. All three genes are osmotically inducible to some degree. betL is
      transcribed from a sigma(B)-independent promoter, while gbuA is transcribed from
      dual promoters, one of which is sigma(B) dependent. opuC is transcribed
      exclusively from a sigma(B)-dependent promoter. The betL promoter is similar in
      sequence to the sigma(B)-independent gbuAP1 promoter. Kinetic analysis of
      transcript accumulation after osmotic upshift demonstrated that sigma(B)
      dependent transcripts from gbuAP2 and sigB accumulate for an extended period
      after upshift, suggesting that sigma(B) activity may provide a mechanism for
      sustained high-level expression during osmotic challenge. In contrast to osmotic
      upshift, expression from the sigma(B)-dependent opuC and gbuAP2 promoters after
      temperature upshift and ethanol stress was minimal, suggesting that additional
      mechanisms may also participate in regulating transcription from these sigma(B)
      dependent promoters.

PMID- 14729707
TI  - Reduced transaminase B (IlvE) activity caused by the lack of yjgF is dependent on
      the status of threonine deaminase (IlvA) in Salmonella enterica serovar
      Typhimurium.
AB  - The YjgF/YER057c/UK114 family is a highly conserved class of proteins that is
      represented in the three domains of life. Thus far, a biochemical function
      demonstrated for these proteins in vivo or in vitro has yet to be defined. In
      several organisms, strains lacking a YjgF homolog have a defect in branched-chain
      amino acid biosynthesis. This study probes the connection between yjgF and
      isoleucine biosynthesis in Salmonella enterica. In strains lacking yjgF the
      specific activity of transaminase B, catalyzing the last step in the synthesis of
      isoleucine, was reduced. In the absence of yjgF, transaminase B activity could be
      restored by inhibiting threonine deaminase, the first enzymatic step in
      isoleucine biosynthesis. Strains lacking yjgF showed an increased sensitivity to
      sulfometruron methyl, a potent inhibitor of acetolactate synthase. Based on work
      described here and structural reports in the literature, we suggest a working
      model in which YjgF has a role in protecting the cell from toxic effects of
      imbalanced ketoacid pools.

PMID- 14729708
TI  - The trans-acting protein interacting with the DNA motif proximal to the
      transcriptional start site of plant L-asparaginase is bacterial sarcosine
      oxidase.
AB  - A trans-acting protein interacting with a specific sequence motif proximal to the
      transcriptional start site of the L-asparaginase promoter has been observed
      previously (E. Vincze, J. M. Reeves, E. Lamping, K. J. F. Farnden, and P. H. S.
      Reynolds, Plant Mol. Biol. 26:303-311, 1994). Gel retardation experiments in
      which protein extracts of Mesorhizobium loti and developing nodules were used
      suggested a bacterial origin for the repressor binding protein (rep2037).
      Nodulation tests were performed by using different Fix(-) Tn5 mutants of M. loti.
      Analyses of these mutants revealed a correlation between the presence of
      Mesorhizobium in the nodule-like structures and the ability of nodule protein
      extracts to bind the repressor binding domain (RBD). Through the use of mutated
      RBD sequences, the RBD sequence was identified as CTAAAAT. The repressor protein
      was isolated from M. loti NZP2037 by multiple chromatographic procedures and
      affinity separation by using concatemers of RBD attached to magnetic beads.
      Sequencing of the recovered protein resulted in identification of the repressor
      protein as the sarcosine oxidase alpha subunit. This was confirmed by expression
      of the gene encoding the M. loti alpha subunit of sarcosine oxidase in
      Escherichia coli. When the expressed peptide was bound to RBD, the gel
      retardation result was identical to the result obtained with rep2037 from M. loti
      strain NZP2037.

PMID- 14729709
TI  - Regulation of the tryptophan biosynthetic genes in Bacillus halodurans: common
      elements but different strategies than those used by Bacillus subtilis.
AB  - In Bacillus subtilis, an RNA binding protein called TRAP regulates both
      transcription and translation of the tryptophan biosynthetic genes. Bacillus
      halodurans is an alkaliphilic Bacillus species that grows at high pHs. Previous
      studies of this bacterium have focused on mechanisms of adaptation for growth in
      alkaline environments. We have characterized the regulation of the tryptophan
      biosynthetic genes in B. halodurans and compared it to that in B. subtilis. B.
      halodurans encodes a TRAP protein with 71% sequence identity to the B. subtilis
      protein. Expression of anthranilate synthetase, the first enzyme in the pathway
      to tryptophan, is regulated significantly less in B. halodurans than in B.
      subtilis. Examination of the control of the B. halodurans trpEDCFBA operon both
      in vivo and in vitro shows that only transcription is regulated, whereas in B.
      subtilis both transcription of the operon and translation of trpE are controlled.
      The attenuation mechanism that controls transcription in B. halodurans is similar
      to that in B. subtilis, but there are some differences in the predicted RNA
      secondary structures in the B. halodurans trp leader region, including the
      presence of a potential anti-antiterminator structure. Translation of trpG, which
      is within the folate operon in both bacilli, is regulated similarly in the two
      species.

PMID- 14729710
TI  - Binding of SycH chaperone to YscM1 and YscM2 activates effector yop expression in
      Yersinia enterocolitica.
AB  - Yersinia enterocolitica transports YscM1 and YscM2 via the type III pathway, a
      mechanism that is required for the establishment of bacterial infections. Prior
      to host cell contact, YscM1 and YscM2 exert posttranscriptional regulation to
      inhibit expression of effector yop genes, which encode virulence factors that
      travel the type III pathway into the cytoplasm of macrophages. Relief from
      repression has been predicted to occur via the type III secretion of YscM1 and
      YscM2 into the extracellular medium, resulting in the depletion of regulatory
      molecules from the bacterial cytoplasm. Using digitonin fractionation and
      fluorescence microscopy of FlAsH-labeled polypeptides in Yersinia-infected cells,
      we have localized YscM1 and YscM2 within the host cell cytoplasm. Type III
      injection of YscM1 and YscM2 required the SycH chaperone. Expression of C
      terminal fusions of YscM1 and YscM2 to the neomycin phosphotransferase reporter
      revealed sequences required for regulatory activity and for secretion in the
      absence of SycH. Coexpression of SycH and glutathione S-transferase (GST)-YscM1
      or GST-YscM2, hybrid GST variants that cannot be transported by the type III
      apparatus, also relieved repression of Yop synthesis. GST-SycH bound to YscM1 and
      YscM2 and activated effector yop expression without initiation of the bound
      regulatory molecules into the type III pathway. Further, regulation of yop
      expression by YscM1, YscM2, and SycH is shown to act independently of factors
      that regulate secretion, and gel filtration chromotography revealed populations
      of YscM1 and YscM2 that are not bound to SycH under conditions where Yop
      synthesis is repressed. Taken together, these results suggest that YscM1- and
      YscM2-mediated repression may be relieved through binding to the cytoplasmic
      chaperone SycH prior to their type III injection into host cells.

PMID- 14729712
TI  - Regulation of L-alanine dehydrogenase in Rhizobium leguminosarum bv. viciae and
      its role in pea nodules.
AB  - Alanine dehydrogenase (AldA) is the principal enzyme with which pea bacteroids
      synthesize alanine de novo. In free-living culture, AldA activity is induced by
      carboxylic acids (succinate, malate, and pyruvate), although the best inducer is
      alanine. Measurement of the intracellular concentration of alanine showed that
      AldA contributes to net alanine synthesis in laboratory cultures. Divergently
      transcribed from aldA is an AsnC type regulator, aldR. Mutation of aldR prevents
      induction of AldA activity. Plasmid-borne gusA fusions showed that aldR is
      required for transcription of both aldA and aldR; hence, AldR is autoregulatory.
      However, plasmid fusions containing the aldA-aldR intergenic region could
      apparently titrate out AldR, sometimes resulting in a complete loss of AldA
      enzyme activity. Therefore, integrated aldR::gusA and aldA::gusA fusions, as well
      as Northern blotting, were used to confirm the induction of aldA activity. Both
      aldA and aldR were expressed in the II/III interzone and zone III of pea nodules.
      Overexpression of aldA in bacteroids did not alter the ability of pea plants to
      fix nitrogen, as measured by acetylene reduction, but caused a large reduction in
      the size and dry weight of plants. This suggests that overexpression of aldA
      impairs the ability of bacteroids to donate fixed nitrogen that the plant can
      productively assimilate. We propose that the role of AldA may be to balance the
      alanine level for optimal functioning of bacteroid metabolism rather than to
      synthesize alanine as the sole product of N(2) reduction.

PMID- 14729713
TI  - Transferrin-binding protein B of Neisseria meningitidis: sequence-based
      identification of the transferrin-Binding site confirmed by site-directed
      mutagenesis.
AB  - A sequence-based prediction method was employed to identify three ligand-binding
      domains in transferrin-binding protein B (TbpB) of Neisseria meningitidis strain
      B16B6. Site-directed mutagenesis of residues located in these domains has led to
      the identification of two domains, amino acids 53 to 57 and 240 to 245, which are
      involved in binding to human transferrin (htf). These two domains are conserved
      in an alignment of different TbpB sequences from N. meningitidis and Neisseria
      gonorrhoeae, indicating a general functional role of the domains. Western blot
      analysis and BIAcore and isothermal titration calorimetry experiments
      demonstrated that site-directed mutations in both binding domains led to a
      decrease or abolition of htf binding. Analysis of mutated proteins by circular
      dichroism did not provide any evidence for structural alterations due to the
      amino acid replacements. The TbpB mutant R243N was devoid of any htf-binding
      activity, and antibodies elicited by the mutant showed strong bactericidal
      activity against the homologous strain, as well as against several heterologous
      tbpB isotype I strains.

PMID- 14729714
TI  - The left end of IS2: a compromise between transpositional activity and an
      essential promoter function that regulates the transposition pathway.
AB  - Cut-and-paste (simple insertion) and replicative transposition pathways are the
      two classical paradigms by which transposable elements are mobilized. A novel
      variation of cut and paste, a two-step transposition cycle, has recently been
      proposed for insertion sequences of the IS3 family. In IS2 this variation
      involves the formation of a circular, putative transposition intermediate (the
      minicircle) in the first step. Two aspects of the minicircle may involve its
      proposed role in the second step (integration into the target). The first is the
      presence of a highly reactive junction formed by the two abutted ends of the
      element. The second is the assembly at the minicircle junction of a strong hybrid
      promoter which generates higher levels of transposase. In this report we show
      that IS2 possesses a highly reactive minicircle junction at which a strong
      promoter is assembled and that the promoter is needed for the efficient
      completion of the pathway. We show that the sequence diversions which
      characterize the imperfect inverted repeats or ends of this element have evolved
      specifically to permit the formation and optimal function of this promoter. While
      these sequence diversions eliminate catalytic activity of the left end (IRL) in
      the linear element, sufficient sequence information essential for catalysis is
      retained by the IRL in the context of the minicircle junction. These data confirm
      that the minicircle is an essential intermediate in the two-step transposition
      pathway of IS2.

PMID- 14729715
TI  - Transcriptional profiling of colicin-induced cell death of Escherichia coli
      MG1655 identifies potential mechanisms by which bacteriocins promote bacterial
      diversity.
AB  - We report the transcriptional response of Escherichia coli MG1655 to damage
      induced by colicins E3 and E9, bacteriocins that kill cells through inactivation
      of the ribosome and degradation of chromosomal DNA, respectively. Colicin E9
      strongly induced the LexA-regulated SOS response, while colicin E3 elicited a
      broad response that included the induction of cold shock genes, symptomatic of
      translational arrest. Colicin E3 also increased the transcription of cryptic
      prophage genes and other laterally acquired mobile elements. The transcriptional
      responses to both these toxins suggest mechanisms that may promote genetic
      diversity in E. coli populations, pointing to a more general role for colicins in
      adaptive bacterial physiology than has hitherto been realized.

PMID- 14729716
TI  - DNA binding by the meningococcal RdgC protein, associated with pilin antigenic
      variation.
AB  - The RdgC protein of Neisseria gonorrhoeae is required for efficient pilin
      antigenic variation, although its precise role has yet to be established. We
      demonstrate that the nearly identical RdgC from Neisseria meningitidis binds DNA
      with little specificity for sequence or structure, like the Escherichia coli
      protein. We also show that neither protein is able to constrain torsional tension
      in relaxed DNA. These data exclude several possible roles for RdgC in pilin
      antigenic variation and suggest that RdgC performs a similar function in both E.
      coli and the Neisseria spp.

PMID- 14729717
TI  - Four novel genes required for optimal photoautotrophic growth of the
      cyanobacterium Synechocystis sp. strain PCC 6803 identified by in vitro
      transposon mutagenesis.
AB  - Four novel Synechocystis sp. strain PCC 6803 genes (sll1495, sll0804, slr1306,
      and slr1125) which encode hypothetical proteins were determined by transposon
      mutagenesis to be required for optimal photoautotrophic growth. Mutations were
      also recovered in ccmK4, a carboxysome coat protein homologue, and me, the
      decarboxylating NADP(+)-dependent malic enzyme. This is the first report that
      these known genes are required for optimal photoautotrophy.

PMID- 14729718
TI  - Inhibiting cell division in Escherichia coli has little if any effect on gene
      expression.
AB  - DNA microarrays were used to compare gene expression in dividing and nondividing
      (filamentous) cultures of Escherichia coli. Although cells from these cultures
      differed profoundly in morphology, their gene expression profiles were nearly
      identical. These results extend previous evidence that there is no division
      checkpoint in E. coli, and progression through the cell cycle is not regulated by
      the transcription of different genes during different parts of the cell cycle.

PMID- 14729719
TI  - Motility of urease-deficient derivatives of Helicobacter pylori.
AB  - Early studies of a ureB mutant derivative of Helicobacter pylori had suggested
      that urease is needed for motility and that urease action helps energize
      flagellar rotation. Here we report experiments showing that motility is
      unaffected by deletion of ureA and ureB (urease genes) or by inactivation of ureB
      alone, especially if H. pylori strains used as recipients for transformation with
      mutant alleles are preselected for motility. This result was obtained with the
      strain used in the early studies (CPY3401) and also with 15 other strains, 3 of
      which can colonize mice. We conclude that urease is not needed for H. pylori
      motility.

PMID- 14729721
TI  - Hog barn dust extract augments lymphocyte adhesion to human airway epithelial
      cells.
AB  - The dust of hog confinement facilities induces airway inflammation. Mechanisms by
      which this dust modulates inflammation are not completely defined, although it is
      clear that exposure to dust can modulate both epithelial cell and inflammatory
      cell function. In this work, we demonstrate that airway epithelial cell (BEAS-2B)
      treatment with hog barn dust extract (HDE) results in augmentation of peripheral
      blood lymphocyte adhesion to epithelial cell cultures in vitro. The augmentation
      of lymphocyte adhesion to epithelial cells is dependent on the concentration of
      HDE and time of HDE exposure, with twofold increases observed by 3 h and
      maintained at 24 h. Similar results are seen with primary human bronchial
      epithelial cells in culture. Lymphocyte adhesion to epithelial cells is inhibited
      in a concentration-dependent fashion by the treatment of epithelial cells with
      antibody to intercellular adhesion molecule-1 (ICAM-1). In addition, HDE exposure
      of epithelial cells results in an approximate twofold increase in ICAM-1
      expression as determined by flow cytometry analysis. Pretreatment of epithelial
      cells with a protein kinase C-alpha (PKC-alpha) inhibitor, Go-6976, also
      inhibited subsequent lymphocyte adhesion to HDE-exposed epithelial cells. These
      data suggest that airway epithelial cell HDE exposure enhances subsequent
      lymphocyte adhesion to epithelial cells that is mediated in part by HDE
      modulation of ICAM-1 expression and PKC-alpha.

PMID- 14729720
TI  - Expression of Vibrio vulnificus capsular polysaccharide inhibits biofilm
      formation.
AB  - Vibrio vulnificus is a human pathogen that produces lethal septicemia in
      susceptible persons, and the primary virulence factor for this organism is
      capsular polysaccharide (CPS). The role of the capsule in V. vulnificus biofilms
      was examined under a variety of conditions, by using either defined CPS mutants
      or spontaneous CPS expression phase variants derived from multiple strains. CPS
      expression was shown to inhibit attachment and biofilm formation, which
      contrasted with other studies describing polysaccharides as integral to biofilms
      in related species.

PMID- 14729722
TI  - Aging, opioid-receptor agonists and antagonists, and the vestibulosympathetic
      reflex in humans.
AB  - Animal studies indicate that opioids inhibit the firing rate of vestibular
      neurons, which are important in mediating the vestibulosympathetic reflex.
      Furthermore, this inhibition appears to be greater in more mature rats. In the
      present study, we tested the hypotheses that opioids inhibit the
      vestibulosympathetic reflex in humans and that endogenous opioids contribute to
      the age-related impairment of the vestibulosympathetic reflex. These hypotheses
      were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood
      pressure, and heart rate responses to otolith organ engagement during head-down
      rotation (HDR) in young (24 +/- 2 yr old) and older (63 +/- 2 yr) subjects before
      and after administration of either an opioid-receptor antagonist (16 mg naloxone
      in 9 young and 8 older subjects) or an opioid-receptor agonist (60 mg codeine in
      7 young and 7 older subjects). Naloxone did not augment the reflex increase in
      MSNA during HDR in young (Delta7 +/- 2 vs. Delta4 +/- 2 bursts/min and Delta81 +/
      23 vs. Delta60 +/- 24% change in burst frequency and total MSNA before and after
      naloxone, respectively) or older subjects (Delta2 +/- 2 vs. Delta1 +/- 2
      burst/min and Delta8 +/- 7 vs. Delta8 +/- 9% before and after naloxone).
      Similarly, codeine did not attenuate the increase in MSNA during HDR in young
      (Delta8 +/- 1 vs. Delta7 +/- 2 bursts/min and Delta53 +/- 4 vs. Delta64 +/- 16%
      before and after codeine) or older subjects (Delta6 +/- 4 vs. Delta3 +/- 3
      bursts/min and Delta38 +/- 21 vs. Delta33 +/- 20%). Mean arterial blood pressure
      and heart rate responses to HDR were not altered by either naloxone or codeine.
      These data do not provide experimental support for the concept that opioids
      modulate the vestibulosympathetic reflex in humans. Moreover, endogenous opioids
      do not appear to contribute the age-associated impairment of the
      vestibulosympathetic reflex.

PMID- 14729724
TI  - Influence of expiratory loading and hyperinflation on cardiac output during
      exercise.
AB  - Patients with obstructive lung disease are exposed to expiratory loads (ELs) and
      dynamic hyperinflation as a consequence of expiratory flow limitation. To
      understand how these alterations in lung mechanics might affect cardiac function,
      we examined the influence of a 10-cm H2O EL, alone and in combination with
      voluntary hyperinflation (ELH), on pulmonary pressures [esophageal (Pes) and
      gastric (Pg)] and cardiac output (CO) in seven healthy subjects. CO was
      determined by using an acetylene method at rest and at 40 and 70% of peak work.
      At rest and during exercise, EL resulted in an increase in Pes and Pg (7-18 cm
      H2O; P < 0.05) and a decrease in CO (from 5.3 +/- 1.8 to 4.5 +/- 1.4, 12.2 +/-
      2.2 to 11.2 +/- 2.2, and 16.3 +/- 3.3 to 15.2 +/- 3.2 l/min for rest, 40% peak
      work, and 70% peak work, respectively; P < 0.05), which remained depressed after
      an additional 2 min of EL. With ELH, CO increased at rest and both exercise loads
      (relative to EL only) but remained below control values. The changes in CO were
      due to a reduction in stroke volume with a tendency for stroke volume to fall
      further with prolonged EL. There was a negative correlation between CO and the
      increase in expiratory Pes and Pg with EL (R = -0.58 and -0.60; P < 0.01),
      whereas the rise in CO with subsequent hyperinflation was related to a more
      negative Pes (R = 0.72; P < 0.01). In conclusion, EL leads to a reduction in CO,
      which appears to be primarily related to increases in expiratory abdominal and
      intrathoracic pressure, whereas ELH resulted in an improved CO, suggesting that
      lung inflation has little impact on cardiac function.

PMID- 14729723
TI  - Hemodynamic response and oxygen transport in pigs resuscitated with maleimide
      polyethylene glycol-modified hemoglobin (MP4).
AB  - Cell-free Hb increases systemic and pulmonary pressure and resistance and reduces
      cardiac output and heart rate in animals and humans, effects that have limited
      their clinical development as "blood substitutes." The primary aim of this study
      was to evaluate the hemodynamic response to infusion of several formulations of a
      new polyethylene glycol (PEG)-modified human Hb [maleimide PEG Hb (MalPEGHb)] in
      swine, an animal known to be sensitive to Hb-induced vasoconstriction.
      Anesthetized animals underwent controlled hemorrhage (50% of blood volume),
      followed by resuscitation (70% of shed volume) with 10% pentastarch (PS), 4%
      MalPEG-Hb in lactated Ringer (MP4), 4% MalPEG-Hb in pentastarch (HS4), 2% MalPEG
      Hb in pentastarch (HS2), or 4% stroma-free Hb in lactated Ringer solution (SFH).
      Compared with baseline, restoration of blood volume after resuscitation was
      similar and not significantly different for the PS (103%), HS2 (99%), HS4 (106%),
      and MP4 (87%) animals but significantly less for the SFH animals (66%) (P <
      0.05). All solutions that contained MalPEG-Hb restored mean arterial and
      pulmonary pressure and cardiac output. Systemic vascular resistance was
      unchanged, and pulmonary arterial pressure and resistance were increased
      slightly. Both systemic and pulmonary vascular resistance increased significantly
      in animals that received SFH, despite less adequate blood volume restoration.
      Oxygen consumption was maintained in all animals that received MalPEG-Hb, but not
      PS. Base excess improved only with MalPEG-Hb and PS, but not SFH. Red blood cell
      O2 extraction was significantly increased in animals that received Hb, regardless
      of formulation. These data demonstrate resuscitation with MalPEG-human Hb without
      increasing systemic vascular resistance and support our previous observations in
      animals suggesting that the efficacy of low concentrations of PEG-Hb in the
      plasma results from reduced vasoconstriction.

PMID- 14729725
TI  - Exercise training changes autonomic cardiovascular balance in mice.
AB  - Experiments were performed to investigate the influence of exercise training on
      cardiovascular function in mice. Heart rate, arterial pressure, baroreflex
      sensitivity, and autonomic control of heart rate were measured in conscious,
      unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise
      training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex
      sensitivity was evaluated by the tachycardic and bradycardic responses induced by
      sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart
      rate and intrinsic heart rate were determined by use of methylatropine and
      propranolol. Resting bradycardia was observed in trained mice compared with
      sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean
      arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3
      mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained
      group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas
      baroreflex-mediated bradycardia was not altered by training. The tachycardia
      induced by methylatropine was significantly increased in trained animals (139 +/-
      12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was
      significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained
      vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion,
      dynamic exercise training in mice induced a resting bradycardia and an
      improvement in baroreflex-mediated tachycardia. These changes are likely related
      to an increased vagal and decreased sympathetic tone, similar to the exercise
      response observed in humans.

PMID- 14729726
TI  - Effects of five consecutive nocturnal hypoxic exposures on the cerebrovascular
      responses to acute hypoxia and hypercapnia in humans.
AB  - The effects of discontinuous hypoxia on cerebrovascular regulation in humans are
      unknown. We hypothesized that five nocturnal hypoxic exposures (8 h/day) at a
      simulated altitude of 4,300 m (inspired O2 fraction = approximately 13.8%) would
      elicit cerebrovascular responses that are similar to those that have been
      reported during chronic altitude exposures. Twelve male subjects (26.6 +/- 4.1
      yr, mean +/- SD) volunteered for this study. The technique of end-tidal forcing
      was used to examine cerebral blood flow (CBF) and regional cerebral O2 saturation
      (Sr(O2)) responses to acute variations in O2 and CO2 twice before, immediately
      after, and 5 days after the overnight hypoxic exposures. Transcranial Doppler
      ultrasound was used to assess CBF, and near-infrared spectroscopy was used to
      assess Sr(O2). Throughout the nocturnal hypoxic exposures, end-tidal Pco2
      decreased (P < 0.001) whereas arterial O2 saturation increased (P < 0.001)
      compared with overnight normoxic control measurements. Symptoms associated with
      altitude illness were significantly greater than control values on the first
      night (P < 0.001) and second night (P < 0.01) of nocturnal hypoxia. Immediately
      after the nocturnal hypoxic intervention, the sensitivity of CBF to acute
      variations in O2 and CO2 increased 116% (P < 0.01) and 33% (P < 0.05),
      respectively, compared with control values. Sr(O2) was highly correlated with
      arterial O2 saturation (R2 = 0.94 +/- 0.04). These results show that
      discontinuous hypoxia elicits increases in the sensitivity of CBF to acute
      variations in O2 and CO2, which are similar to those observed during chronic
      hypoxia.

PMID- 14729727
TI  - Relationship between blood velocity and conduit artery diameter and the effects
      of smoking on vascular responsiveness.
AB  - Transient changes in arterial diameter in response to transient ischemia-induced
      changes in arterial blood velocity have been used as an index of vascular health.
      The purpose of this study was to determine the relationship between blood
      velocity and diameter in the brachial artery by different methods of increasing
      blood velocity. Acute cigarette smoking was used with otherwise healthy young
      occasional smokers to determine the influence of endothelial-nitric oxide
      pathways on the arterial diameter-blood velocity relationship. Nine nonsmokers
      and 12 occasional smokers (<1 pack/wk) were tested. Blood flow to the forearm was
      manipulated to indirectly investigate the relationship between blood velocity and
      diameter in the brachial artery. Blood flow to forearm was manipulated through
      the use of 1) 5-min ischemia; 2) handgrip exercise; 3) indirect local heating;
      and 4) 5-min ischemia plus indirect local heating. A strong relationship was
      observed between blood velocity and diameter independent of the method used to
      increase blood velocity (R(2) = 0.89). The mean slope of the velocity-diameter
      relationship was not different between nonsmokers and occasional smokers who
      abstained from smoking at least 2 days. Acute smoking did not alter the slope of
      the velocity-diameter relationship although the mean intercept was decreased as a
      result of consistent vasoconstriction (7-10%). The mechanisms by which smoking
      impairs vascular health are largely unknown. These findings differ from previous
      smoking studies that used chronic and/or heavier smokers. The velocity-diameter
      relationship appears independent of the method for increasing velocity. Acute
      smoking in occasional smokers results in vasoconstriction without altering
      vascular responsiveness. The velocity-diameter relationship may be a useful
      measure of the progression of vascular disease.

PMID- 14729728
TI  - Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth
      muscle cell.
AB  - Remodeling of the airway smooth muscle (ASM) cell has been proposed to play an
      important role in airway hyperresponsiveness. Using a functional assay, we have
      assessed remodeling of the cultured rat ASM cell and the role of heat shock
      protein (HSP) 27 in that process. To probe remodeling dynamics, we measured
      spontaneous motions of an individual Arg-Gly-Asp-coated microbead that was
      anchored to the cytoskeleton. We reasoned that the bead could not move unless the
      microstructure to which it is attached rearranged; if so, then its mean square
      displacement (MSD) would report ongoing internal reorganizations over time. Each
      bead displayed a random, superdiffusive motion; MSD increased with time as
      approximately t(1.7), whereas an exponent of unity would be expected for a simple
      passive diffusion. Increasing concentrations of cytochalasin-D or latrunculin-A
      caused marked increases in the MSD, whereas colchicine did not. Treatments with
      PDGF or IL-1beta, but not transforming growth factor-beta, caused decreases in
      the MSD, the extent of which rank-ordered with the relative potency of these
      agents in eliciting the phosphorylation of HSP27. The chemical stressors
      anisomycin and arsenite each increased the levels of HSP27 phosphorylation and,
      at the same time, decreased bead motions. In particular, arsenite prevented and
      even reversed the effects of cytochalasin-D on bead motions. Finally, ASM cells
      overexpressing phospho-mimicking human HSP27, but not wild-type or
      phosphorylation-deficient HSP27, exhibited decreases in bead motions that were
      comparable to the arsenite response. Taken together, these results show that
      phosphorylated HSP27 favors reduced bead motions that are probably due to
      stabilization of the actin cytoskeleton.

PMID- 14729729
TI  - Characterizing airway and alveolar nitric oxide exchange during tidal breathing
      using a three-compartment model.
AB  - Exhaled nitric oxide (NO) may be a useful marker of lung inflammation, but the
      concentration is highly dependent on exhalation flow rate due to a significant
      airway source. Current methods for partitioning pulmonary NO gas exchange into
      airway and alveolar regions utilize multiple exhalation flow rates or a single
      breath maneuver with a preexpiratory breath hold, which is cumbersome for
      children and individuals with compromised lung function. Analysis of tidal
      breathing data has the potential to overcome these limitations, while still
      identifying region-specific parameters. In six healthy adults, we utilized a
      three-compartment model (two airway compartments and one alveolar compartment) to
      identify two potential flow-independent parameters that represent the average
      volumetric airway flux (pl/s) and the time-averaged alveolar concentration
      (parts/billion). Significant background noise and distortion of the signal from
      the sampling system were compensated for by using a Gaussian wavelet filter and a
      series of convolution integrals. Mean values for average volumetric airway flux
      and time-averaged alveolar concentration were 2,500 +/- 2,700 pl/s and 3.2 +/-
      3.4 parts/billion, respectively, and were strongly correlated with analogous
      parameters determined from vital capacity breathing maneuvers. Analysis of
      multiple tidal breaths significantly reduced the standard error of the parameter
      estimates relative to the single-breath technique. Our initial assessment
      demonstrates the potential of utilizing tidal breathing for noninvasive
      characterization of pulmonary NO exchange dynamics.

PMID- 14729730
TI  - Influence of exercise on dilatation of the basilar artery during diabetes
      mellitus.
AB  - Our goal was to examine whether exercise training alleviates impaired nitric
      oxide synthase (NOS)-dependent dilatation of the basilar artery in Type 1
      diabetic rats. To test this hypothesis, we measured in vivo diameter of the
      basilar artery in sedentary and exercised nondiabetic and diabetic rats in
      response to NOS-dependent (acetylcholine) and -independent (nitroglycerin)
      agonists. To determine the potential role for nitric oxide in vasodilatation in
      sedentary and exercised nondiabetic and diabetic rats, we examined responses
      after NG-monomethyl-l-arginine (l-NMMA). We found that acetylcholine produced
      dilatation of the basilar artery that was similar in sedentary and exercised
      nondiabetic rats. Acetylcholine produced only minimal vasodilatation in sedentary
      diabetic rats. However, exercise alleviated impaired acetylcholine-induced
      vasodilatation in diabetic rats. Nitroglycerin produced dilatation of the basilar
      artery that was similar in sedentary and exercised nondiabetic and diabetic rats.
      l-NMMA produced similar inhibition of acetylcholine-induced dilatation of the
      basilar artery in sedentary and exercised nondiabetic and diabetic rats. Finally,
      we found that endothelial NOS (eNOS) protein in the basilar artery was higher in
      diabetic compared with nondiabetic rats and that exercise increased eNOS protein
      in the basilar artery of nondiabetic and diabetic rats. We conclude that 1)
      exercise can alleviate impaired NOS-dependent dilatation of the basilar artery
      during diabetes mellitus, 2) the synthesis and release of nitric oxide accounts
      for dilatation of the basilar artery to acetylcholine in sedentary and exercised
      nondiabetic and diabetic rats, and 3) exercise may exert its affect on
      cerebrovascular reactivity during diabetes by altering levels of eNOS protein in
      the basilar artery.

PMID- 14729731
TI  - Developmental changes in the expression of GABAA receptor subunits alpha1,
      alpha2, and alpha3 in the rat pre-Botzinger complex.
AB  - Previously, we reported that the pre-Botzinger complex (PBC) exhibited a dramatic
      reduction in cytochrome oxidase activity at postnatal day (P) 12. This coincided
      in time with decreases in glutamate and NMDA receptor subunit 1 and increases in
      GABA, GABAB, glycine receptor, and glutamate receptor GluR2. To test our
      hypothesis that various alpha-subunits of GABAA receptors also undergo changes in
      their expression during postnatal development, as they do in other brain regions,
      we undertook an in-depth immunohistochemical study of GABAA receptor subunits
      alpha1, alpha2, and alpha3 in the PBC of P0 to P21 rats. We found that 1) GABAA
      alpha3-subunit was expressed at relatively high levels at P0, which then declined
      with age; 2) GABAA alpha1-subunit was expressed at relatively low levels at P0
      but increased with age; 3) the developmental trends of subunits alpha1 and alpha3
      intersected at P12; and 4) GABAA alpha2-subunit expression was moderate to light
      at P0 and remained quite constant during development, being lowest at P21. These
      findings suggest that the apparent switch in relative expressions of subunits
      alpha3 and alpha1 during development and the intersection of slopes around P12
      may be associated with possible changes in GABAA receptor subtypes that would
      mediate different functional properties of GABA transmission, such as primarily a
      less efficient inhibitory transmission before P12 and a more mature inhibitory
      effect at P12 and thereafter, as suggested by the kinetics of distinct
      postsynaptic potentials. This mechanism may contribute partially to the dramatic
      reduction in cytochrome oxidase activity within the PBC at P12, as shown
      previously.

PMID- 14729732
TI  - Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is
      increased with hypoxia.
AB  - This study investigated the effects of prolonged exercise performed in normoxia
      (N) and hypoxia (H) on neuromuscular fatigue, membrane excitability, and Na+-K+ 
      ATPase activity in working muscle. Ten untrained volunteers [peak oxygen
      consumption (Vo2peak) = 42.1 +/- 2.8 (SE) ml x kg(-1) x min(-1)] performed 90 min
      of cycling during N (inspired oxygen fraction = 0.21) and during H (inspired
      oxygen fraction = 0.14) at approximately 50% of normoxic Vo2peak. During N, 3-O
      methylfluorescein phosphatase activity (nmol x mg protein(-1) x h(-1)) in vastus
      lateralis, used as a measure of Na+-K+-ATPase activity, decreased (P < 0.05) by
      21% at 30 min of exercise compared with rest (101 +/- 53 vs. 79.6 +/- 4.3) with
      no further reductions observed at 90 min (72.8 +/- 8.0). During H, similar
      reductions (P < 0.05) were observed during the first 30 min (90.8 +/- 5.3 vs.
      79.0 +/- 6.3) followed by further reductions (P < 0.05) at 90 min (50.5 +/- 3.9).
      Exercise in N resulted in reductions (P < 0.05) in both quadriceps maximal
      voluntary contractile force (MVC; 633 +/- 50 vs. 477 +/- 67 N) and force at low
      frequencies of stimulation, namely 10 Hz (142 +/- 16 vs. 86.7 +/- 10 N) and 20 Hz
      (283 +/- 32 vs. 236 +/- 31 N). No changes were observed in the amplitude,
      duration, and area of the muscle compound action potential (M wave). Exercise in
      H was without additional effect in altering MVC, low-frequency force, and M-wave
      properties. It is concluded that, although exercise in H resulted in a greater
      inactivation of Na+-K+-ATPase activity compared with N, neuromuscular fatigue and
      membrane excitability are not differentially altered.

PMID- 14729733
TI  - Serum and sputum concentrations following the oral administration of linezolid in
      adult patients with cystic fibrosis.
AB  - OBJECTIVES: Linezolid is a new oxazolidinone antibiotic with efficacy against a
      broad range of Gram-positive bacteria, including methicillin-resistant
      Staphylococcus aureus (MRSA). In this study, we have determined the serum and
      sputum linezolid concentrations in adults with cystic fibrosis (CF) following
      oral drug administration. METHODS: Eleven adult patients with CF were recruited.
      Subjects received 600 mg of linezolid orally every 12 h for a total of six doses.
      Serum and sputum levels were measured just before and at 2 h after the final dose
      of linezolid. A further serum level was measured at 4 h. RESULTS: Ten adult
      patients completed the study. Mean (s.d.) serum linezolid concentrations were 2.3
      mg/L (1.5) at 12 h following the fifth dose. At 2 and 4 h following the sixth
      dose, concentrations were 13.5 (4.3) and 8.1 (3.3). Mean (s.d.) linezolid sputum
      concentrations were 3.6 (2.1) and 17.4 (7.2) mg/L at 0 and 2 h following drug
      administration. CONCLUSIONS: The oral administration of linezolid results in good
      sputum penetration in patients with CF. Mean levels exceed the required MIC for
      the treatment of MRSA for >80% of the dosing period for serum and the majority of
      the dosing period for sputum.

PMID- 14729735
TI  - Neisseria meningitidis showing decreased susceptibility to ciprofloxacin: first
      report in Spain.

PMID- 14729734
TI  - Mutations of the rpoB gene in rifampicin-resistant Streptococcus pneumoniae in
      Taiwan.
AB  - OBJECTIVE: To determine the mechanism of rifampicin resistance in Streptococcus
      pneumoniae in Taiwan. METHODS: Rifampicin resistance was investigated with
      respect to the rpoB gene in 23 invasive S. pneumoniae isolates collected from
      1996 to 2001. PCR and molecular typing were used for genetic and epidemiological
      analyses. Transformation was used to determine the functional gene for
      resistance. RESULTS: Twenty-two of 23 isolates carried at least one mutation at
      either cluster I or III of rpoB; the most frequent mutation found in 21 isolates
      (91%) was histidine (H499) to asparagine or tyrosine at position 499, followed by
      isoleucine to valine (I624V) at position 624 in 16 isolates (70%), tyrosine to
      phenylalanine (Y589F) at position 589 in 14 isolates (60.9%) and isoleucine to
      valine (I608V) at position 608 in 13 isolates (56.5%). Less-frequent mutations
      were also identified: D489V, R597F, N623E, N623S, N669D, Q671K, Y674F and A683V.
      High-level rifampicin resistance was observed in isolates with a mutation at
      position 499 or 489. Mutations other than at position 499 or 489 played little
      role in or had no relation to rifampicin resistance. No dominant epidemic strain
      was observed with ribotyping, multilocus sequence typing, or serotyping.
      CONCLUSIONS: Rifampicin resistance among multidrug-resistant S. pneumoniae in
      Taiwan was mostly caused by rpoB mutations.

PMID- 14729736
TI  - Antibiotic-induced persistence of cytotoxic Staphylococcus aureus in non
      phagocytic cells.
AB  - OBJECTIVES: After infection of non-phagocytic cells, some Staphylococcus aureus
      strains are able to survive and kill their host cells. The purpose of this study
      was to determine the action of various antibiotics on the survival of host cells
      and/or intracellular S. aureus. METHODS: Murine keratinocyte (PAM212) and
      fibroblast (mKSA) cell lines were infected with cytotoxic S. aureus and cultured
      in the presence of various antibiotics at graded concentrations. The viability of
      host cells was measured 24 h after infection. To determine the bacterial
      viability within host cells, cellular lysates were prepared and colony forming
      units were quantified using a spiral plater. Host cells infected with fluorescein
      isothiocyanate (FITC)-labelled S. aureus were analysed by flow cytometry and
      microscopy to determine the subcellular localization S. aureus. RESULTS:
      Oxacillin, vancomycin, gentamicin, ciprofloxacin and
      trimethoprim/sulfamethoxazole did not rescue host cells from cell death induced
      by intracellular S. aureus. In contrast, linezolid, rifampicin, azithromycin,
      clindamycin, erythromycin and quinupristin/dalfopristin suppressed the cytotoxic
      action of S. aureus. After withdrawal of antibiotics, intracellular S. aureus
      regained cytotoxic activity and killed their host cells. Only rifampicin was able
      to eliminate intracellular S. aureus completely within 72 h. In contrast,
      clindamycin, azithromycin and linezolid induced a state of intracellular
      persistence of viable S. aureus. CONCLUSIONS: Antibiotics commonly used for the
      management of S. aureus infections appear to create a niche for invasive
      intracellular S. aureus, which may play an important role for persistence and
      recurrence of infection. Because of its unique ability to eliminate intracellular
      S. aureus, rifampicin appears to be valuable for the treatment of invasive S.
      aureus infections.

PMID- 14729737
TI  - Role of the 'cre/blr-tag' DNA sequence in regulation of gene expression by the
      Aeromonas hydrophila beta-lactamase regulator, BlrA.
AB  - OBJECTIVES: To further understand the mechanisms used to regulate expression of
      the blr regulon of Aeromonas hydrophila T429125, including three unlinked beta
      lactamase genes, ampH, cepH and imiH, and to examine the role of the 'cre/blr
      tag' DNA sequence (TTCAC) in transcriptional control exerted by the two-component
      system, BlrAB. METHODS: Genes linked to blrAB-ampH were cloned using standard
      methods; gene expression was measured by RT-PCR or beta-lactamase assays;
      transcription start sites were determined by reversed-transcript analysis; cepH
      promoter probe reporter constructs including cre/blr-tag deletions were generated
      by PCR; and BlrA was overexpressed in Escherichia coli using the pBAD plasmid.
      RESULTS: The blrD gene, encoding a putative inner membrane protein, was found to
      be located downstream of blrAB-ampH. RT-PCR analysis showed that blrD is part of
      the A. hydrophila blr regulon, and transcript start-point determinations revealed
      that blr-regulon promoters (including that of blrD) are preceded by at least one
      cre/blr-tag. Targeted deletion of the 16 bp cepH cre/blr-tag dimer blocked BlrA
      induced overproduction of cepH in E. coli. CONCLUSIONS: This is the first report
      of non-beta-lactamase genes being co-ordinately regulated with a normally co
      resident beta-lactamase gene, and the first direct evidence for a role of the
      cre/blr-tag sequence in the regulation of transcription by BlrA.

PMID- 14729738
TI  - Enhancement of antibiotic activity by sub-lethal concentrations of enterocin
      CRL35.
AB  - OBJECTIVE: The aim of this study was to evaluate the interaction of several
      conventional antibiotics with sub-lethal concentrations of enterocin CRL35, a
      cationic peptide, on Listeria innocua 7. METHODS: Susceptibility of L. innocua 7
      cells to the combination of enterocin CRL35 and non-peptide antibiotics
      (cefalexin, ampicillin, ciprofloxacin, nalidixic acid, erythromycin,
      chloramphenicol, vancomycin and tetracycline) was assayed using the broth
      dilution method and killing curves. Fractional inhibitory concentration (FIC)
      index was calculated to assess synergy. The transmembrane electrical potential
      and pH gradient were determined by specific fluorescent probes. RESULTS: We found
      positive interactions between the cationic peptide and three conventional
      antibiotics (tetracycline, erythromycin and chloramphenicol) which are excluded
      from the cells by efflux pumps dependent on the membrane proton gradient.
      Furthermore, enterocin CRL35 even at sub-lethal concentrations induced the
      dissipation of both components of the proton motive force (Deltap), i.e.
      transmembrane electrical potential and pH gradient and hence the alteration of
      processes dependent on it. CONCLUSION: We hypothesize that enterocin CRL35
      increases the effectiveness of these antibiotics by impairment of the bacterial
      active efflux systems and the consequent accumulation of these toxic compounds in
      the cytoplasm.

PMID- 14729739
TI  - In vitro and in vivo activity of meropenem and sulbactam against a multidrug
      resistant Acinetobacter baumannii strain.
AB  - OBJECTIVES: The potential therapeutic role of meropenem combined with sulbactam
      against a clinical endemic isolate of multidrug-resistant Acinetobacter
      baumannii, Ab-153, was investigated. METHODS: The antimicrobial susceptibility of
      Ab-153 to various drugs was studied by the agar dilution method and Etest strips.
      The antibacterial activity of meropenem and sulbactam were investigated by a time
      kill study in vitro and further examined for therapeutic efficacy in vivo in a
      murine model. RESULTS: In the time-kill study, at a concentration of 0.5 x MIC (4
      mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only
      the combination demonstrated bactericidal effects and there was at least a 5
      log(10) reduction in bacterial colony counts after 48 h, compared with either
      drug alone. BALB/c mice infected with 2.1-2.6 x 10(7) cfu of Ab-153 were treated
      with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in
      combination. The survival rate of mice in the combination group was significantly
      higher than that in the meropenem-treated or sulbactam-treated group (87% versus
      35%, P = 0.0004; 87% versus 30%, P = 0.0002). CONCLUSIONS: Meropenem in
      conjunction with sulbactam can exhibit more potent antimicrobial activity against
      Ab-153 than meropenem or sulbactam alone.

PMID- 14729740
TI  - Antimicrobial susceptibility of Salmonella isolated from cattle, swine and
      poultry (2001-2002): report from the Japanese Veterinary Antimicrobial Resistance
      Monitoring Program.
AB  - OBJECTIVES: The Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM)
      Program was established in 1999 to examine the susceptibility of bacteria from
      food-producing animals to antimicrobial agents. This study tested the
      susceptibility of Salmonella isolates collected during 2001-2002 to 20
      antimicrobials. MATERIALS AND METHODS: MICs of antimicrobial agents were
      determined using the NCCLS agar dilution method, and interpreted according to
      breakpoints obtained from the bimodal MIC distributions. RESULTS: A total of 82
      Salmonella were isolated from food-producing animals and tested for antimicrobial
      susceptibility. Isolates resistant to ampicillin, dihydrostreptomycin, kanamycin,
      oxytetracycline, chloramphenicol, bicozamycin, nalidixic acid, oxolinic acid and
      trimethoprim were obtained from healthy animals and diagnostic sample
      submissions. Salmonella Dublin was isolated only from cattle and showed
      resistance to older quinolones. Resistance to ampicillin, dihydrostreptomycin,
      kanamycin and oxytetracycline was common across all serotypes. Fluoroquinolone
      resistant Salmonella Choleraesuis was isolated from swine and was the first
      Japanese report on this type of resistance in Salmonella from an animal origin.
      Most Salmonella Typhimurium isolates showed resistance to ampicillin,
      chloramphenicol, dihydrostreptomycin and oxytetracycline. S. Typhimurium DT104
      accounted for 40.7% of S. Typhimurium isolates and was more often multi-drug
      resistant. Most Salmonella Infantis isolates from poultry showed resistance to
      dihydrostreptomycin, oxytetracycline, trimethoprim or kanamycin. In Salmonella
      Enteritidis, the major serotype isolated from food-poisoning in Japan, only
      resistance to dihydrostreptomycin was observed. CONCLUSIONS: This is the first
      JVARM report of Salmonella isolates, and continuous investigations at the
      national level on antimicrobial resistance in Salmonella isolated from food
      producing animals will be important in the JVARM Program.

PMID- 14729741
TI  - Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and
      reduces levofloxacin-induced resistance in penicillin-resistant pneumococci.
AB  - Ceftriaxone acted synergistically with levofloxacin in time-killing assays in
      vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and
      KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard
      method, showing FIC indices of 0.25. In the experimental rabbit meningitis model,
      ceftriaxone (1x 125 mg/kg) was slightly less bactericidal (-0.30 Deltalog(10)
      cfu/mL(.)h) compared with levofloxacin (-0.45 Deltalog(10) cfu/mL(.)h) against
      the penicillin-resistant strain WB4. The combination therapy (levofloxacin and
      ceftriaxone) was significantly superior (-0.64 Deltalog(10) cfu/mL(.)h) to either
      monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a
      sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the
      two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC
      increased 64-fold in both strains versus a 16-fold increase with the combination
      (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced
      resistance was confirmed by mutations detected in the genes parC and gyrA,
      encoding for subunits of topoisomerase IV and gyrase, respectively. The addition
      of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in
      both strains.

PMID- 14729742
TI  - In vitro activity and mode of action of diastereomeric antimicrobial peptides
      against bacterial clinical isolates.
AB  - OBJECTIVES: Increasing resistance of pathogenic bacteria to antibiotics is a
      severe problem in health care and has intensified the search for novel drugs.
      Cationic antibacterial peptides are the most abundant antibiotics in nature and
      have been frequently proposed as new anti-infective agents. Here, a group of
      diastereomeric (containing d- and l-amino acids) peptides is studied regarding
      their potency against multiply resistant clinical isolates and their modes of
      action against Gram-positive cocci. METHODS: MIC determinations and chequerboard
      titrations followed established procedures. Mode of action studies included
      killing kinetics and a series of experiments designed to characterize the impact
      of the diastereomeric peptides on bacterial membranes. RESULTS: The tested
      diastereomers displayed high antimicrobial and broad spectrum activity with
      amphipathic-2D being the most active peptide. Synergic activities were observed
      with individual strains. Mode of action studies clearly demonstrated that the
      cytoplasmic membrane is a primary target for the peptides and that membrane
      disruption constitutes a significant bactericidal activity for the major fraction
      of a bacterial population. However, depending on the indicator strain, the
      results also suggest that additional molecular events contribute to the overall
      activity.

PMID- 14729743
TI  - Preventative use of antifungal drugs in patients treated for cancer.
AB  - Prophylactic use of antifungal compounds has more or less become standard
      clinical practice for patients who are treated for a haematological malignancy.
      However, apart from the prevention of infections by Candida species in bone
      marrow transplant recipients and a possible reduction in invasive aspergillosis
      in high-risk patients, there is little evidence to justify this approach.
      Antifungals ought to be administered to patients on their perceived individual
      risk and better studies should be conducted to provide a more rational basis for
      our clinical decisions. Results of studies in specific populations should not be
      used to create guidelines for other patient groups or general populations.
      Antifungals are potentially toxic and overuse might be associated with
      unnecessary direct and indirect drug-related costs.

PMID- 14729744
TI  - Genetic analysis of 17 genes in Staphylococcus aureus with reduced susceptibility
      to vancomycin (VISA) and heteroVISA.

PMID- 14729745
TI  - Linezolid compared with teicoplanin for the treatment of suspected or proven Gram
      positive infections.
AB  - The efficacy, safety and tolerability of linezolid was compared with teicoplanin
      in a randomized, controlled, open-label, multicentre study of 430 patients with
      suspected or proven Gram-positive infection. Patients received intravenous (iv)
      +/- oral linezolid 600 mg every 12 h (n = 215) or iv or intramuscular teicoplanin
      (n = 215) for up to 28 days. Clinical outcomes in the intent-to-treat (ITT) and
      clinically-evaluable populations and microbiological success rates in
      microbiologically evaluable patients were assessed at follow-up (test of cure).
      Investigator assessed clinical cure rates at end of treatment (EOT) in ITT
      patients treated with linezolid (95.5%) were superior to those of teicoplanin
      (87.6%) for all infections combined, indicating a 7.9% statistically significant
      treatment advantage for linezolid (P = 0.005, 95% CI: 2.5, 13.2). Clinical cure
      rates by baseline diagnosis were consistently higher at EOT for the linezolid
      versus teicoplanin groups with skin and soft tissue infection (96.6% versus
      92.8%), pneumonia (96.2% versus 92.9%) and bacteraemia (88.5% versus 56.7%). The
      31.8% treatment advantage in bacteraemic patients (but not for those seen in the
      other infection categories) for linezolid-treated patients was statistically
      significant (P = 0.009, 95% CI: 10.2, 53.4). Bacterial eradication rates for
      linezolid exceeded those of teicoplanin for all infection sites combined but this
      did not reach statistical significance (81.9% versus 69.8%, respectively; P =
      0.056). Adverse event rates were similar between the treatment groups, were mild
      to moderate in severity, and resolved quickly following treatment. The linezolid
      group experienced a higher incidence of drug related adverse events (30% versus
      17%; P = 0.002), and notably of gastrointestinal effects (13.0% versus 1.9%, P =
      0.001). However, antibiotic discontinuation rates as a result of drug related
      adverse events were similar (4.7% in the linezolid group versus 3.7%). Linezolid
      was clinically superior to teicoplanin in the treatment of Gram-positive
      infections.

PMID- 14729746
TI  - Effect of moxifloxacin versus imipenem/cilastatin treatment on the mortality of
      mice infected intravenously with different strains of Bacteroides fragilis and
      Escherichia coli.
AB  - OBJECTIVES: To study the effect of moxifloxacin versus imipenem/cilastatin
      (hereafter referred to as imipenem) treatment on the mortality of mice infected
      intravenously with different strains of Bacteroides fragilis and Escherichia
      coli. METHODS: Groups of 20 mice each were infected intravenously with different
      strains of B. fragilis [moxifloxacin and imipenem susceptible or resistant, and
      enterotoxin (ET) positive or negative] and E. coli (moxifloxacin and imipenem
      susceptible). Twenty-four hours post-infection, intravenous therapy with either
      moxifloxacin (2.0 mg twice a day) or imipenem (2.4 mg three times a day) was
      started and continued for 3 days. Control groups were left untreated. Survival
      rates were recorded at day 7 post-infection. At that time, surviving mice were
      killed and numbers of bacteria in the liver and kidneys were determined. RESULTS:
      If compared with untreated animals, mice treated with either moxifloxacin or
      imipenem showed significantly improved survival (P < 0.001). There was no
      significant difference (P = 0.97) in the survival rates comparing the two
      treatment regimens irrespective of the ET positivity or the susceptibility to
      moxifloxacin or imipenem of the infective B. fragilis strain. However, there was
      a tendency that B. fragilis was recovered more often from the liver and kidneys
      of mice infected with ET positive strains. CONCLUSIONS: The data show that
      moxifloxacin was as efficacious as imipenem in reducing the mortality rate of
      mice suffering from a severe systemic aerobic/anaerobic infection.

PMID- 14729747
TI  - Biofilms, homoserine lactones and biocide susceptibility.
AB  - AIMS: To investigate the susceptibility, to a range of different biocides, of
      Pseudomonas aeruginosa strains variously deficient in N-acyl homoserine lactone
      systems, grown either as planktonic or biofilm populations. METHODS AND RESULTS:
      Biocide susceptibility data were generated for strains of P. aeruginosa deficient
      in N-acyl homoserine lactone production, grown planktonically or as biofilm
      populations using a poloxamer hydrogel construct. Component cells from the
      biofilm constructs were also tested for their susceptibility. Significant
      differences in susceptibility were noted between the wild-type strain, a mutant
      defective in the long chain (C-12) homoserine lactone and a mutant defective in
      the short chain (C-4) homoserine lactone which could not be related to the
      biofilm mode of growth. Moreover, differences in susceptibility appeared to be
      dependent upon the nature of the homoserine lactone deletion and type of biocide
      rather than the mode of growth. CONCLUSIONS: No general trend exists between
      homoserine lactone deficiency and biocide susceptibility regardless of mode of
      growth.

PMID- 14729748
TI  - Activity of gemifloxacin against Streptococcus pneumoniae and Haemophilus
      influenzae.
AB  - This review focuses on the activity of gemifloxacin, a new respiratory
      fluoroquinolone, against the two most important bacterial pathogens associated
      with lower respiratory tract infections, namely Streptococcus pneumoniae and
      Haemophilus influenzae.

PMID- 14729749
TI  - Susceptibility of Candida albicans biofilms grown in a constant depth film
      fermentor to chlorhexidine, fluconazole and miconazole: a longitudinal study.
AB  - OBJECTIVES: The aim of this study was to assess the resistance of Candida
      albicans biofilms to both antifungal and antimicrobial agents in vitro. METHODS:
      Biofilms of C. albicans were grown on denture acrylic discs in a constant depth
      film fermentor and maintained with artificial saliva. The MIC of fluconazole,
      miconazole and chlorhexidine for C. albicans was first determined. Using these
      data, 72 h biofilms were exposed to these agents at different MIC levels. In
      order to assess growth, biofilms were removed from the fermentor, incubated in
      the test agent for various periods, the biofilms disrupted and the viable yeast
      cells present determined. The MIC for these cells was then also determined. In a
      separate experiment, biofilms of various ages (2-72 h) were exposed to sub
      biofilm MIC concentrations for two different periods. RESULTS: C. albicans
      biofilms were found to be highly resistant to fluconazole and miconazole compared
      with the same cells grown in suspension (>/=1024 x MIC). In contrast,
      chlorhexidine inhibited the growth of C. albicans biofilms at a concentration up
      to 8 x MIC. When the susceptibility of biofilms over time was investigated,
      higher reductions were observed for chlorhexidine and miconazole than fluconazole
      for biofilms of 2 and 6 h. CONCLUSIONS: We have shown in this study that the
      susceptibility of C. albicans to antifungal and antimicrobial agents changes
      throughout biofilm development.

PMID- 14729750
TI  - Oropharyngeal carriage of macrolide-resistant viridans group streptococci: a
      prevalence study among healthy adults in Belgium.
AB  - OBJECTIVES: Viridans group streptococci (VGS) are gaining significance as
      reservoirs of resistance determinants for respiratory tract pathogens. Our aim
      was to investigate healthy adults for oropharyngeal carriage of VGS that are
      resistant to macrolides, as well as to other common antibiotics. METHODS:
      Macrolide-resistant VGS were isolated from throat samples of 154 healthy Belgian
      adults, and phenotyped and genotyped for erm(A), erm(B) and mef(A). In vitro
      susceptibilities to 10 antimicrobials and the presence of tetracycline resistance
      genes were also determined. RESULTS: Carriage was detected in 71% of the
      population screened, from whom 157 unique, macrolide-resistant VGS were isolated.
      A constitutive (cMLS) phenotype was present in 105 isolates, of which 102
      isolates carried either erm(B) or erm(B) + mef(A). The remaining three isolates
      did not present with any of the genes studied. All 45 isolates showing the M
      phenotype carried mef(A). The least abundant inducible (iMLS) isolates (n = 7)
      carried either erm(B) or erm(B) + mef(A). The most abundant macrolide-resistant
      VGS species was Streptococcus mitis (51%). Co-resistance to tetracycline was
      identified in 114 isolates, of which tet(M) was present in 105, tet(O) in two and
      both tet(M) and tet(O) in one, while the remaining six isolates did not present
      with either gene. tet(M) was also present in four tetracycline susceptible and
      two intermediately resistant isolates. Fluoroquinolone resistance (ciprofloxacin
      MIC > or = 4 mg/L) was detected in 16 isolates. Resistance to telithromycin,
      penicillin and chloramphenicol was appreciably low. CONCLUSIONS: This study
      highlights a high oropharyngeal carriage of macrolide-resistant VGS and its co
      resistance to tetracycline and fluoroquinolones among healthy Belgian adults.

PMID- 14729751
TI  - Iron enhances the antituberculous activity of pyrazinamide.
AB  - BACKGROUND: Pyrazinamide is a paradoxical frontline tuberculosis drug
      characterized by high in vivo sterilizing activity but poor in vitro activity.
      This separation in pyrazinamide activity reflects differences between the in vivo
      tissue environment and in vitro culture conditions. The well-known acid pH
      requirement for pyrazinamide activity was discovered previously based on such
      reasoning but does not completely explain the discrepancy between in vivo and in
      vitro activity of pyrazinamide. This study examined the effect of iron, which
      could potentially be elevated in local inflammatory lesions, on pyrazinamide
      activity in vitro. MATERIALS AND METHODS: The effect of iron on the activity of
      pyrazinamide or its active derivative pyrazinoic acid against Mycobacterium
      tuberculosis was assessed in liquid medium in a drug exposure assay or in solid
      medium with pyrazinamide plus iron or pyrazinamide alone. The effect of iron on
      pyrazinamide or pyrazinoic acid was expressed as percentage of growth inhibition.
      RESULTS: We have shown that iron enhances the activity of pyrazinamide and
      pyrazinoic acid against M. tuberculosis in both liquid and solid media at acid pH
      5.6. Iron enhanced the activity of pyrazinoic acid but not pyrazinamide against
      the naturally pyrazinamide-resistant Mycobacterium bovis BCG. Other metal ions
      such as magnesium, calcium and zinc did not enhance the activity of pyrazinamide
      or pyrazinoic acid. CONCLUSIONS: Iron increased the activity of pyrazinamide or
      pyrazinoic acid against M. tuberculosis in vitro. These findings may have
      implications for the study of mechanism of action of pyrazinamide and possible
      iron supplement for improving the activity of pyrazinamide.

PMID- 14729752
TI  - Comment on: effect of antiretroviral protease inhibitors alone, and in
      combination with paromomycin, on the excystation, invasion and in vitro
      development of Cryptosporidium parvum.

PMID- 14729753
TI  - Comparative studies on the efficacy of AmBisome and Fungizone in a mouse model of
      disseminated aspergillosis.
AB  - OBJECTIVES: The efficacy of intravenous injections of a liposomal formulation of
      amphotericin B (AmBisome) and amphotericin B deoxycholate (Fungizone) was
      evaluated in immunocompetent and temporarily leucopenic mouse models of
      disseminated aspergillosis using seven isolates of Aspergillus. METHODS: Mice
      were infected with the organisms via tail veins. At 4 h after infection,
      antifungals were administered intravenously. For 30 days the number of mice
      surviving was recorded. RESULTS: AmBisome at 1 mg/kg or higher significantly
      prolonged the survival time of mice infected with five out of seven isolates of
      Aspergillus compared with the control group. There was no difference in in vivo
      activity between AmBisome and Fungizone at 1 mg/kg in six isolates of
      Aspergillus. At the maximum tolerated dose of antifungals, however, AmBisome (10
      mg/kg) showed greater efficacy than Fungizone (1 mg/kg). CONCLUSIONS: These
      results suggest that the overall protective activity of AmBisome against
      disseminated aspergillosis is superior to that of Fungizone.

PMID- 14729754
TI  - Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression
      by endothelial cells: a possible factor in the pathogenesis of infusion
      phlebitis.
AB  - OBJECTIVES: Antimicrobial agents are important risk factors for infusion
      phlebitis, but the risk varies between different antibiotics. Erythromycin and
      dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic
      effects on cultured endothelial cells. The pathogenesis of infusion phlebitis is
      unclear, but chemical toxicity is thought to lead to inflammation and subsequent
      thrombosis. In the present study, endothelial cells were exposed to antibiotics
      at the range of concentrations used for intravenous administration, followed by
      analysis of pro-inflammatory and pro-coagulant surface molecules. METHODS:
      Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid
      cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin
      and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing. After 5 or 24
      h additional incubation, cells were analysed for E-selectin (CD62E), tissue
      factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow
      cytometry. RESULTS: Despite constitutive expression of ICAM-1 (34%) in HUVEC,
      6250 mg/L of dicloxacillin or erythromycin significantly increased the number of
      cells with ICAM-1 expression by 37% and 30%, respectively. In contrast,
      cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background
      levels. A similar pattern was seen with the endothelial cell line EaHy926. The E
      selectin and TF density were not affected by the antibiotics examined.
      CONCLUSIONS: The results of this study support the theory that endothelial cells
      that are affected by high concentrations of antibiotics may initiate an
      inflammatory response through expression of ICAM-1. This is a novel finding in
      the pathogenesis of infusion phlebitis.

PMID- 14729755
TI  - Pharmacodynamic study of beta-lactams alone and in combination with beta
      lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible beta
      lactamase.
AB  - OBJECTIVES: The antimicrobial efficacies of beta-lactams alone and in combination
      with beta-lactamase inhibitors were investigated by applying a rabbit tissue cage
      model against a strain of Pseudomonas aeruginosa with an inducible AmpC (iAmpC)
      beta-lactamase. METHODS: Two sterilized golf Wiffle balls were surgically
      implanted in the rabbit dorsal cervical area. After 4 weeks, Wiffle balls had
      filled with tissue cage fluid (TCF), in which 2 mL of 10(6) cfu/mL of the test
      isolate were inoculated. To achieve the same T > MIC as in humans, 400 mg/kg of
      the beta-lactams alone and in combination was administered twice a day via
      subcutaneous injection. The dosing regimens were as follows: piperacillin alone,
      4 g piperacillin/0.5 g tazobactam; ticarcillin alone, 3 g ticarcillin/0.1 g
      clavulanate; and 3 g ticarcillin/ 0.3 g clavulanate. RESULTS: The changes in
      bacterial counts (log cfu/mL) after the 3 day treatments were as follows: 1.03 +/
      0.97 (control), -1.31 +/- 0.61 (piperacillin), -2.81 +/- 0.53 (4 g
      piperacillin/0.5 g tazobactam), -1.61 +/- 0.68 (ticarcillin), -3.42 +/- 0.75 (3 g
      ticarcillin/0.1 g clavulanate) and -1.65 +/- 1.47 log cfu/mL (3 g ticarcillin/0.3
      g clavulanate). AmpC induction by high-dose clavulanate was observed in rabbit
      TCF, and was confirmed by the in vitro induction study. CONCLUSIONS: The study
      indicated that tazobactam significantly enhanced the antibacterial activity of
      piperacillin against iAmpC P. aeruginosa; clavulanate had synergy with the
      antibacterial activity of ticarcillin at low concentration, but had no effect on
      ticarcillin at high concentration due to AmpC induction by clavulanate.

PMID- 14729756
TI  - Treatment of cutaneous leishmaniasis among travellers.
AB  - Leishmaniasis is endemic in 88 countries on five continents. There are 1-1.5
      million cases of cutaneous leishmaniasis reported yearly worldwide. There has
      been a sharp increase in recorded cases over the last 10 years. Based on
      geographical distribution, cutaneous leishmaniasis is divided into Old World and
      New World leishmaniasis. In the past, species could be inferred from geographical
      setting or determined by performing culture and isoenzyme analysis. The recently
      developed and now widely available PCR technology allows a rapid diagnosis with
      determination of most species, and thus enables a species-orientated treatment.
      While the Old World species mostly cause benign and often self-limiting cutaneous
      disease, the American species cause a broad spectrum of conditions from benign to
      severe manifestations, including mucosal involvement. The response to treatment
      varies according to the species. Therefore, a species-specific approach is
      proposed. Drugs for systemic and topical treatment are presented and discussed
      with regard to their application, use and adverse effects. Indications for local
      or systemic treatment are proposed. Drugs under investigation are also mentioned.
      An overview of published treatment options and a treatment recommendation is
      given for each of the most important species. The level of evidence of the
      studies leading to these recommendations is given.

PMID- 14729757
TI  - In vitro activities of spectinomycin and comparator agents against Pasteurella
      multocida and Mannheimia haemolytica from respiratory tract infections of cattle.
AB  - OBJECTIVES: Prior to the renewal of spectinomycin licensing for veterinary uses
      in Germany, 154 Pasteurella multocida and 148 Mannheimia haemolytica strains from
      respiratory tract infections in cattle were investigated for their MICs of
      spectinomycin and other antimicrobial agents. The data obtained should serve as a
      baseline from which to judge the future development of resistance. Moreover, the
      in vitro activity of spectinomycin in comparison with other antimicrobials should
      be assessed. METHODS: MIC determination for all 302 strains was performed by the
      broth dilution method and evaluated according to NCCLS standards. MIC(50) and
      MIC(90) values were calculated. Strains resistant to spectinomycin were subjected
      to PCR assays for genes known to mediate spectinomycin resistance in Gram
      negative and Gram-positive bacteria. RESULTS: With the exception of resistance to
      sulfamethoxazole in P. multocida and M. haemolytica, and resistance to ampicillin
      in M. haemolytica, an overall low level of resistance was detected. A total of
      93.5% of the P. multocida and 98.6% of the M. haemolytica strains were
      susceptible to spectinomycin, with MIC(90)s of 32 mg/L. PCR analysis showed that
      none of the spectinomycin-resistant strains carried any of the aadA gene
      subtypes, nor the genes spc or aad(9). CONCLUSIONS: Prior to the renewal of
      spectinomycin, only a small number of spectinomycin-resistant strains was
      detected among bovine P. multocida and M. haemolytica. The genes responsible for
      spectinomycin resistance in these strains seemed to be different from those so
      far known to occur in other Gram-negative and Gram-positive bacteria.

PMID- 14729758
TI  - Comparisons of the in vitro susceptibility testing results for garenoxacin using
      six different national methods: report from the garenoxacin international
      bridging study.
AB  - BACKGROUND: Laboratories worldwide carry out MIC/disc diffusion (DD) tests using
      various national methods, often published by local organizations. Potentially
      different results may complicate drug development or registration between the US
      methods and those used in the European Union (EU). This study uses a new des
      F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized
      antimicrobial susceptibility testing methods. METHODS: Investigators in France,
      Germany, Spain, Sweden and the UK tested two bacterial collections designated,
      challenge (CC; n = 330) containing quinolone-resistant strains and national (NC;
      n = 540) that were recent clinical isolates (2000-2001). Results were compared
      with values derived from the National Committee for Clinical Laboratory Standards
      (NCCLS) methods, carried out by the US coordinating site. Discords (greater than
      four-fold) between MIC method results were repeated. Results were analysed for
      variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by
      regression statistics. Ciprofloxacin was used as the control quinolone agent.
      RESULTS: CC and NC testing compliance averaged 98.4% and 86.4% among
      participating centres, respectively, and correlation (r) of the national method
      to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96)
      and UK (0.95). CC produced MIC results that were identical to the NCCLS (Spain)
      to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions
      versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK). Similar patterns
      were observed for the NC (r = 0.93-0.98), and all nations had >99% of results
      within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values. MIC results from
      four national methods were slightly elevated compared to the NCCLS result
      (average 0.2 x log(2)). Control ciprofloxacin MIC and DD test results showed
      similar patterns. CONCLUSIONS: Inter-method garenoxacin susceptibility test
      results indicate that MIC and zone diameter endpoints derived from five EU
      methods compare favourably to the NCCLS method results, and generally were
      identical or a fraction of a log(2) dilution step higher. In contrast, zone
      diameters for garenoxacin and ciprofloxacin were routinely larger for the EU
      methods. This unique inter-method 'bridging' experiment allows regulatory
      agencies to better correlate in vitro testing results derived from procedures
      that use different national methodologies.

PMID- 14729759
TI  - Antimicrobial resistance in the nasopharyngeal flora of children with acute
      maxillary sinusitis and maxillary sinusitis recurring after amoxicillin therapy.
AB  - OBJECTIVE: To investigate the antimicrobial susceptibility of the organisms
      isolated from the nasopharynx of children who present with acute maxillary
      sinusitis (AMS) or maxillary sinusitis that recurred (RMS) after amoxicillin
      therapy. METHODS: Analysis of nasopharyngeal cultures obtained from 70 patients,
      42 with AMS and 28 with RMS. RESULTS: Thirty-eight potentially pathogenic
      organisms were recovered in 36 (86%) of the children from the AMS group, and 40
      were isolated from 26 (93%) of the children from the RMS group. The organisms
      isolated were Streptococcus pneumoniae (21 isolates), Haemophilus influenzae non
      type b (17), Moraxella catarrhalis (15), Streptococcus pyogenes (13) and
      Staphylococcus aureus (12). Resistance to the eight antimicrobial agents used was
      found in 34 instances in the AMS group compared to 93 instances in the RMS group
      (P < 0.005). The difference between AMS and RMS was significant with S.
      pneumoniae resistance to amoxicillin (P < 0.0025), to co-amoxiclav (P < 0.0025),
      to trimethoprim-sulfamethoxazole (P < 0.05), to cefixime (P < 0.05), and to
      azithromycin (P < 0.05), and for H. influenzae to amoxicillin (P < 0.025).
      CONCLUSIONS: These data illustrate the higher recovery rate of antimicrobial
      resistant S. pneumoniae and H. influenzae from the nasopharynx of children who
      had maxillary sinusitis that recurred after amoxicillin therapy than those with
      AMS.

PMID- 14729760
TI  - Trends in prescribing antibiotics for children in Dutch general practice.
AB  - OBJECTIVE: To assess changes in antibiotic prescribing patterns for children
      between 1987 and 2001, and to identify general practice characteristics
      associated with higher antibiotic prescribing rates. METHODS: Cross-sectional
      national survey of Dutch general practice in 1987 and 2001. Data were used for
      all children aged 0-17 years; 86 577 children in 103 participating practices in
      1987, and 76 010 children in 90 participating practices in 2001. Population
      based, contact-based and disease-based antibiotic prescription rates were
      evaluated by age, gender and diagnosis. Practice characteristics associated with
      inappropriate broad-spectrum antibiotic prescription were identified. RESULTS:
      Population-based prescription rates decreased from 300/1000 children (95% CI, 292
      307) in 1987 to 232/1000 children in 2001 (95% CI, 228-235). In 1987, the contact
      based prescription rate was 108/1000 contacts (95% CI, 106-111) and this was
      somewhat similar in 2001: 103/1000 contacts (95% CI, 101-105). In 2001, increased
      disease-based prescription rates were observed for acute otitis media, acute
      bronchitis, acute upper airway infections, acute tonsillitis and cough. Overall,
      non-recommended broad-spectrum antibiotics were prescribed more often in 2001
      than in 1987 (87% in 1987 versus 90% in 2001, P < 0.001). Adjusted for other
      practice characteristics, general practitioners in single-handed practices
      prescribed 58% more broad-spectrum antibiotics inappropriately for upper airway
      infections than general practitioners in group practices. CONCLUSION: Antibiotic
      prescribing in children is still relatively low in the Netherlands. However, the
      prescription of broad-spectrum antibiotics for inappropriate diagnoses has
      increased, an unfavourable trend given the emerging bacterial resistance. Single
      handed practices should especially be targeted to improve antibiotic prescribing
      in children.

PMID- 14729761
TI  - BRO beta-lactamase alleles, antibiotic resistance and a test of the BRO-1
      selective replacement hypothesis in Moraxella catarrhalis.
AB  - OBJECTIVES: The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of
      the Moraxella catarrhalis BRO beta-lactamase was tested by examining the temporal
      distribution, antibiotic resistance and epidemiological characteristics of
      isolates from a long-term collection at a single locale. METHODS: A rapid, one
      step PCR assay conducted on 354 isolates spanning 1984-1994 distinguished bro
      alleles in over 97% of the beta-lactamase-producing isolates. Probes of dot blots
      were used to distinguish PCR failure from non-beta-lactamase-mediated penicillin
      resistance. RESULTS: BRO-2 isolates comprised 0-10% of the population per year
      with no evidence of a decline over time. All beta-lactamase producers exceeded
      the clinical threshold for penicillin resistance. Bimodality of penicillin MICs
      for beta-lactamase producers was caused by variation within BRO-1 rather than
      differences between BRO-1 and BRO-2. Non-beta-lactamase factors also confer
      resistance to penicillin and may contribute to the BRO-1 bimodality. The 13 BRO-2
      isolates were associated with diverse genotypes within which there was evidence
      of epidemiologically linked clusters. The exclusive association of BRO-2 with
      four unrelated genotypes suggested maintenance of BRO-2 by recurrent mutation or
      horizontal exchange. CONCLUSIONS: The relative rarity of BRO-2 throughout the
      study, the absence of a declining temporal trend, and genetic diversity within
      BRO-2 all failed to support the hypothesis that BRO-2 was more common in the past
      and has been selectively replaced by BRO-1.

PMID- 14729762
TI  - A comparative study of the post-antifungal effect (PAFE) of amphotericin B,
      triazoles and echinocandins on Aspergillus fumigatus and Candida albicans.
AB  - OBJECTIVES: To study the post-antifungal effect (PAFE) of antifungal drugs on
      Aspergillus fumigatus by a radiometric assay and compare the results with those
      obtained for Candida albicans. METHODS: A. fumigatus cultures pregrown for 48 h
      in 96-well microtitre plate were exposed to various concentrations of the
      antifungal drug for 2 h. The drug-treated mycelia were washed, incubated in RPMI
      1640 containing (14)C-labelled amino acids and the accumulation of radioactivity
      in the mycelia at different time intervals was determined. The PAFE was
      determined by plotting the amount of radioactivity associated with the mycelia
      against post-treatment incubation time. The PAFE of antifungal drug on C.
      albicans was examined by determining the multiplication (cfu/mL) of drug
      pretreated cells at different time intervals for 24 h in drug-free medium.
      RESULTS: Amphotericin B produced a prolonged PAFE (7.5 +/- 0.70 h) against A.
      fumigatus whereas itraconazole (0.5 +/- 0.0 h), voriconazole (0.5 +/- 0.0 h),
      posaconazole (0.75 +/- 0.35 h), ravuconazole (0.38 +/- 0.17 h) and the
      echinocandins caspofungin (< or =0.5 h) and micafungin (< or =0.5 h) produced
      short PAFE. Short exposure (1 h) of C. albicans to low concentrations (0.125-1
      mg/L) of amphotericin B (5.3 +/- 1.15 h), caspofungin (5.6 +/- 0.57 h) and
      micafungin (5 +/- 1.0 h) produced prolonged PAFE whereas the triazoles produced a
      short (< or =0.5 h) PAFE. CONCLUSIONS: Determination of (14)C-labelled amino acid
      accumulation in antifungal drug-pretreated mycelia is a suitable method for
      studying PAFE in A. fumigatus. Antifungal drugs with fungicidal activity tend to
      possess longer PAFE compared to fungistatic drugs.

PMID- 14729763
TI  - In vitro antibacterial activity of the peptide PsVP-10 against antimicrobial
      resistant Enterococcus faecalis isolated from clinical samples.
AB  - OBJECTIVE: To analyse the antimicrobial activity of the peptide PsVP-10 against
      67 resistant Enterococcus faecalis strains isolated from clinical samples.
      METHODS: The qualitative disc diffusion method and MIC determinations were used.
      RESULTS: The presence of several multidrug-resistant phenotypes of E. faecalis
      was demonstrated, in which there were high MICs to chloramphenicol, tetracycline,
      vancomycin, cefaloridine, ampicillin and gentamicin. In comparison, the peptide
      PsVP-10 showed lower MICs against all the multidrug-resistant and susceptible E.
      faecalis. CONCLUSIONS: There is an urgent need for the development of novel
      antimicrobial agents against the highly resistant E. faecalis. The present study
      shows that the peptide PsVP-10 might make a contribution to the solution of this
      serious problem.

PMID- 14729764
TI  - Tissue kinetics of telithromycin, the first ketolide antibacterial.
AB  - The potential efficacy of an antibacterial depends not only on its spectrum of
      activity but also on its concentration at the site of infection. The tissue
      kinetics of telithromycin-the first ketolide antibacterial-are reviewed here.
      Telithromycin accumulates rapidly in white blood cells, inflammatory fluid, and
      cells and tissues of the upper and lower respiratory tract, with mean
      concentrations above the MICs of key respiratory pathogens. Tissue kinetics of
      telithromycin support facilitated delivery to the site of infection, good
      efficacy against intracellular respiratory pathogens and respiratory pathogens at
      extracellular sites in the airways, and effectiveness in the treatment of upper
      and lower respiratory tract infections (RTIs). The tissue kinetics profile of
      telithromycin, together with its microbiological profile, makes it a promising
      new antibacterial for the treatment of community-acquired RTIs.

PMID- 14729765
TI  - Modification of phagocytosis and cytokine production in peritoneal and splenic
      murine cells by erythromycin A, azithromycin and josamycin.
AB  - OBJECTIVES: The aim of this study was to determine whether pre-incubation of
      peritoneal or splenic cells with different doses of the macrolides erythromycin A
      (14-membered ring), azithromycin (15-membered ring) and josamycin (16-membered
      ring) affects their phagocytic activity or cytokine production. METHODS:
      Peritoneal and splenic cells from BALB/c mice were pre-incubated with different
      concentrations of these antibiotics, those similar to serum levels attained with
      the treatment schedules used in human therapy. RESULTS: From our observations of
      phagocytic activity and IL-12 production by peritoneal cells, these macrolide
      antibiotics seem to act mainly as immunosuppressive agents, although they induce
      peritoneal cells to increase IL-18 production and splenic cells IL-4 production.
      CONCLUSIONS: Macrolide antibiotics can interfere with the Th1 cell-amplifying
      activity of IL-18 in conjunction with IL-12 and, in contrast, may induce a Th2
      cell response in an IL-4-dependent manner. These results could improve their
      therapeutic use especially in immunosuppressed patients.

PMID- 14729766
TI  - Antibiotic resistance genes, integrons and multiple antibiotic resistance in
      thirty-five serotypes of Salmonella enterica isolated from humans and animals in
      the UK.
AB  - OBJECTIVES: To examine 397 strains of Salmonella enterica of human and animal
      origin comprising 35 serotypes for the presence of aadB, aphAI-IAB, aadA1, aadA2,
      bla(Carb(2)) or pse1, bla(Tem), cat1, cat2, dhfr1, floR, strA, sul1, sul2,
      tetA(A), tetA(B) and tetA(G) genes, the presence of class 1 integrons and the
      relationship of resistance genes to integrons and antibiotic resistance. RESULTS:
      Some strains were resistant to ampicillin (91), chloramphenicol (85), gentamicin
      (2), kanamycin (14), spectinomycin (81), streptomycin (119), sulfadiazine (127),
      tetracycline (108) and trimethoprim (45); 219 strains were susceptible to all
      antibiotics. bla(Carb(2)), floR and tetA(G) genes were found in S. Typhimurium
      isolates and one strain of S. Emek only. Class 1 integrons were found in S. Emek,
      Haifa, Heidelberg, Mbandaka, Newport, Ohio, Stanley, Virchow and in Typhimurium,
      mainly phage types DT104 and U302. These strains were generally multi-resistant
      to up to seven antibiotics. Resistance to between three and six antibiotics was
      also associated with class 1 integron-negative strains of S. Binza, Dublin,
      Enteritidis, Hadar, Manhattan, Mbandaka, Montevideo, Newport, Typhimurium DT193
      and Virchow. CONCLUSION: The results illustrate specificity of some resistance
      genes to S. Typhimurium or non- S. Typhimurium serotypes and the involvement of
      both class 1 integron and non-class 1 integron associated multi-resistance in
      several serotypes. These data also indicate that the bla(Carb(2)), floR and
      tetA(G) genes reported in the SG1 region of S. Typhimurium DT104, U302 and some
      other serotypes are still predominantly limited to S. Typhimurium strains.

PMID- 14729767
TI  - New tools for assessing microvascular obstruction in patients with ST elevation
      myocardial infarction.

PMID- 14729768
TI  - Methotrexate eluting stents: to modify or cure?

PMID- 14729769
TI  - Optimal therapeutic strategies in the setting of post-infarct no reflow: the need
      for a pathogenetic classification.

PMID- 14729770
TI  - The paradoxical finding of mitral valve incompetence and cor triatriatum: a
      mechanism revealed?

PMID- 14729771
TI  - The extents of mitral leaflet opening and closure are determined by left
      ventricular systolic function.

PMID- 14729772
TI  - Atrial pacing for the prevention of atrial fibrillation after coronary artery
      bypass graft surgery: a review of the literature.
AB  - Atrial fibrillation (AF) occurs in 20-40% of patients after coronary artery
      bypass graft surgery (CABG) and contributes to increased morbidity and
      expenditure after CABG. The limited efficacy of pharmacological treatment to
      prevent post-CABG AF has stimulated research into alternative prophylactic
      strategies for the arrhythmia. This article critically reviews the trial evidence
      in the literature regarding the efficacy of epicardial atrial pacing to prevent
      post-CABG AF. Thirteen randomised controlled trials of either right, left, or
      biatrial pacing to prevent post-CABG AF were identified. Overall, prophylactic
      biatrial epicardial pacing appears to be effective prophylaxis against post-CABG
      AF and to reduce postoperative hospital stay. The efficacy of single site right
      or left atrial pacing is less clear. Further data are required to determine both
      the efficacy of single site atrial pacing and the cost effectiveness of pacing
      strategies to prevent AF after CABG.

PMID- 14729773
TI  - Spontaneous termination of ventricular fibrillation.

PMID- 14729774
TI  - Pacing extremely old patients: who decides--the doctor, the patient, or the
      relatives?
AB  - Decision making competence is not necessarily present or absent. In many cases it
      is partial or compromised. This applies especially to those over 80 years old, in
      whom the prevalence of dementia is high. Three patients who presented with
      indications for permanent pacemaker insertion are considered. One was apparently
      competent, one had partial competence, and one was clearly incompetent. In all
      three cases the closest relatives were opposed to decisions made by either the
      patient or the doctors. The three cases reflect the tension between doctors,
      patients, and relatives in situations where medical interests, individual
      interests, and familial interests conflict. The cases illustrate the type of
      problems encountered in clinical practice. The current legal position is
      reviewed.

PMID- 14729775
TI  - Impact of multislice CT on coronary ostial stenosis in Takayasu's arteritis.

PMID- 14729776
TI  - Myocardial hibernation and heart failure: introduction.

PMID- 14729777
TI  - Fundamental concepts in myocardial viability assessment revisited: when knowing
      how much is "alive" is not enough.

PMID- 14729778
TI  - Hibernation and heart failure.

PMID- 14729779
TI  - Infectious endocarditis with an abscess around an aortic prosthesis.

PMID- 14729780
TI  - Surgery for hibernation.

PMID- 14729781
TI  - New support for clarifying the relation between ST segment resolution and
      microvascular function: degree of ST segment resolution correlates with the
      pressure derived collateral flow index.
AB  - OBJECTIVE: To investigate the relation between the degree of ST segment
      resolution (STR) after thrombolysis and the pressure derived collateral flow
      index (CFIp), determined using an intracoronary pressure measurement technique in
      patients with recent myocardial infarction. METHODS: 33 patients were studied.
      TIMI grade III flow was achieved in the infarct related artery by thrombolysis. A
      surface ECG was obtained on admission and 90 minutes later. The sum of ST segment
      elevations was measured by summing all leads with ST elevation on the baseline
      ECG and on the 90 minute ECG (after thrombolysis) and calculating the percentage
      recovery. The study population was divided into two groups, with good STR (> or =
      50%; group 1) or poor STR (< 50%; group 2). After angiography, a fibreoptic
      pressure monitoring guidewire was advanced to the stenosis to be dilated. The
      CFIp was determined as the ratio [coronary wedge pressure - central venous
      pressure]/[mean aortic pressure - central venous pressure]. RESULTS: The mean STR
      on the surface ECG was 54.6% and mean (SD) CFIp was 0.25 (0.12) (range 0.10
      0.41). There was an inverse correlation between the individually calculated
      percentage of STR and CFIp (r = -0.64, p < 0.01). The mean CFIp was lower in
      patients with a good STR than in those with a poor STR (0.18 (0.07) v 0.27
      (0.10), p < 0.02). CONCLUSIONS: Although TIMI grade III flow was achieved after
      thrombolysis, a worse STR on the surface ECG was associated with higher CFIp
      measured in the infarct related artery. CFIp appears to reflect the degree of
      microvascular obstruction by quantifying impedance of the microvasculature.

PMID- 14729782
TI  - Combined membrane covered and uncovered stents for coronary arteriovenous fistula
      associated with atherosclerotic plaque in a patient with acute myocardial
      infarction.

PMID- 14729783
TI  - Increased serum concentrations of soluble CD95/Fas and caspase 1/ICE in patients
      with acute angina.
AB  - OBJECTIVES: To investigate the expression of death inducing receptors in the sera
      of patients with stable and unstable angina. DESIGN: 80 consecutive patients with
      stable (n = 40) or unstable (n = 40) angina pectoris were studied. Serum
      concentrations of soluble CD95 (sCD95), soluble CD95 ligand (sCD95L; CD178),
      tumour necrosis factor (TNF) alpha, soluble TNFalpha receptor type 1 (sTNFR1),
      and interleukin 1beta converting enzyme (ICE; caspase 1) were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Significant increases in the
      concentrations of sCD95 and ICE (p < 0.001 and p < 0.023, respectively) were
      found in the serum from patients with unstable angina relative to those with
      stable angina. There were no significant differences in the concentrations of
      sCD95L, TNF alpha, and sTNFR1 between the groups. CONCLUSIONS: These data provide
      the first evidence that sCD95 and ICE are important serological markers that may
      help to discriminate between stable and unstable angina. This observation may
      warrant further clinical study to elucidate the clinical impact of sCD95 and ICE
      in acute coronary syndromes.

PMID- 14729784
TI  - New combined treatments avoided transplantation in a child with severe pulmonary
      hypertension.

PMID- 14729785
TI  - Hyperuricaemia does not impair cardiovascular function in healthy adults.
AB  - OBJECTIVE: To investigate the possibility that uric acid (UA) can impair
      endothelial function, an important surrogate for atherosclerosis. DESIGN: UA was
      administered locally or systemically to healthy adult men and women in a series
      of randomised placebo controlled studies. This temporarily raised serum UA
      concentrations, so that the potential effects of hyperuricaemia on mechanisms of
      cardiovascular disease could be studied. MAIN OUTCOME MEASURES: The effects of UA
      administration on basal blood flow and responses to locally administered
      acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied
      in the forearm vascular bed with venous occlusion plethysmography. The effects of
      hyperuricaemia on systemic vascular resistance, large artery compliance, and
      baroreflex sensitivity were examined by validated non-invasive techniques.
      RESULTS: UA administration caused a twofold increase in serum concentrations.
      However, there were no acute effects on haemodynamic variables, basal forearm
      blood flow, or nitric oxide dependent endothelial function. CONCLUSION: Unlike
      other risk factors associated with endothelial dysfunction, acute exposure to
      high concentrations of UA does not impair cardiovascular function in healthy men.
      These findings do not support a causal link between hyperuricaemia and
      atherosclerosis.

PMID- 14729787
TI  - Ruptured plaque or embolised thrombus.

PMID- 14729786
TI  - Catheter based intracoronary brachytherapy leads to increased platelet
      activation.
AB  - BACKGROUND: Vascular brachytherapy (VBT) after percutaneous coronary intervention
      (PCI) is associated with a higher risk of stent thrombosis than conventional
      treatment. OBJECTIVE: To investigate in vivo periprocedural platelet activation
      with and without VBT, and to assess a possible direct effect of radiation on
      platelet activation. DESIGN: Of 50 patients with stable angina, 23 received VBT
      after PCI, while 27 had PCI only. The 23 patients who received VBT after PCI were
      pretreated for one month with aspirin and clopidogrel. Platelet activation was
      assessed by flow cytometry. RESULTS: The two patient groups did not differ in
      their platelet activation before the intervention. There was a significant
      increase in activation immediately after VBT, with 21.2% (interquartile range
      13.0% to 37.6%) thrombospondin positive and 54.0% (42.3% to 63.6%) CD 63 positive
      platelets compared with 12.7% (9.8% to 14.9%) thrombospondin positive and 37.9%
      (33.2% to 45.2%) CD 63 positive platelets before the intervention (p < 0.001 and
      p < 0.01, respectively). Patients without VBT had no periprocedural difference in
      platelet activation immediately after PCI. No increase in platelet activation was
      found after ex vivo irradiation of blood samples obtained from healthy controls.
      CONCLUSIONS: Catheter based intracoronary VBT carried out according to current
      standards is highly thrombogenic. The current antithrombotic treatment with
      aspirin and clopidogrel is not sufficient to suppress platelet activation during
      the procedure. From in vitro experiments, it appears that platelet activation
      during brachytherapy is not caused by irradiation but by the procedure of
      catheter based VBT.

PMID- 14729788
TI  - ECGSIM: an interactive tool for studying the genesis of QRST waveforms.
AB  - BACKGROUND: Discussion about the selection of diagnostic features of the ECG and
      their possible interpretation would benefit from a model of the genesis of these
      signals that has a sound basis in electrophysiology as well as in physics. Recent
      advances in computer technology have made it possible to build a simulation
      package whereby the genesis of ECG signals can be studied interactively. DESIGN:
      A numerical method was developed for computing ECG signals on the thorax, as well
      as electrograms on both endocardium and epicardium. The source representation of
      the myocardial electric activity is the equivalent double layer. The transfer
      factors between the electric sources and the resulting potentials on the heart
      surface as well as on the body surface were computed using a realistic thorax
      model. RESULTS AND CONCLUSION: The resulting transfer factors were implemented in
      a simulation program. The program allows the user to make interactive changes in
      the timing of depolarisation and repolarisation on the ventricular surface, as
      well as changing the local source strength, and to inspect or document the effect
      of such changes instantaneously on electrograms and body surface potentials,
      visualised by waveforms as well as by potential maps and movies. The entire
      simulation package can be installed free of charge from www.ecgsim.org.

PMID- 14729789
TI  - Is Mobitz type I atrioventricular block benign in adults?
AB  - OBJECTIVE: To assess the need for pacing in adults with chronic Mobitz type I
      second degree atrioventricular block (Mobitz I). DESIGN: Prospective study.
      SETTING: District general hospital. PATIENTS: 147 subjects aged > or = 20 years
      (age cohorts 20-44, 45-64, 65-79, and > or = 80) with chronic Mobitz I without
      second degree Mobitz II or third degree (higher degree) block on entry, seen from
      1968 to 1993 and followed up to 30 June 1997. Sixty four had organic heart
      disease. The presence of symptomatic bradycardia was defined as highly likely in
      47 patients (class 1); probable in 14 (class 2); and absent in 86 (class 3).
      INTERVENTIONS: Pacemakers were implanted in 90 patients for the following
      indications: symptoms in 74 and prophylaxis in 16. MAIN OUTCOME MEASURES: The
      main outcome measure was death, with conduction deterioration to higher degree
      block or symptomatic bradycardia the alternative measure. RESULTS: Five year
      survival to death was reduced in unpaced patients relative to that expected for
      the normal population (overall mean (SD) 53.5 (6.7)% v 68.6%, p < 0.001; class 3,
      54.4 (7.3)% v 70.1%, p < 0.001). Paced patients fared better than unpaced
      (overall (mean (SD) five year survival 76.3 (4.5)% v 53.5 (6.7)%, p = 0.0014;
      class 3, 87.2 (5.4)% v 54.4 (7.3)%, p = 0.020; and organic heart disease, 68.2
      (7.6)% v 44.0 (9.9)%, p < or = 0.0014). There were no deaths in the < 45 cohort.
      Survival to first outcome (main or alternative) was further reduced to 31.7
      (5.0)% in 102 patients unpaced initially and 34.2 (5.7)% in class 3. Only the 20
      44 cohort and patients with sinus arrhythmia had > 50% survival. CONCLUSION:
      Mobitz I block is not usually benign in patients > or = 45 years of age.
      Pacemaker implantation should be considered, even in the absence of symptomatic
      bradycardia or organic heart disease.

PMID- 14729790
TI  - Pulsed wave Doppler tissue echocardiography assessment of the long axis function
      of the right and left ventricles during the early neonatal period.
AB  - OBJECTIVE: To assess the long axis function of both ventricles during the early
      neonatal period by using pulsed wave Doppler tissue (PWDT) echocardiography.
      DESIGN: PWDT echocardiography was recorded from the lateral sites of the mitral
      and tricuspid annuluses and the tip of interventricular septum in 130 neonates
      within 24 hours after birth (day 0 group), in 135 neonates 1-7 days after birth
      (day 1-7 group), and in 131 healthy children (children group). RESULTS: Peak
      systolic motion velocity (Sw) of the three ventricular walls positively
      correlated with the number of days after birth (p < 0.005). Compared with the
      children group, in neonates Sw in the right ventricle and peak early diastolic
      motion velocity (Ew) and peak atrial systolic motion velocity in the
      interventricular septum were lower than in the remaining two walls (p < 0.0005, p
      < 0.0001, and p< 0.0001, respectively). Although peak mitral and tricuspid flow
      velocities during early diastole (E) correlated with the number of hours after
      birth in the day 0 group, there was no significant change in the Ew of either
      ventricle. The E:Ew ratio of both ventricles was significantly higher in both
      neonate groups than in the children group (p < 0.001). The E:Ew ratio of the left
      ventricle was higher in the day 0 group than in the day 1-7 group (p < 0.005).
      CONCLUSIONS: The two ventricles differ in their normal PWDT echocardiographic
      values and in the parameter change after birth during the early neonatal period,
      which may reflect differences in ventricular adaptation after birth.

PMID- 14729792
TI  - Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon
      angioplasty in acute myocardial infarction.
AB  - OBJECTIVE: To compare the effects of nicorandil (a hybrid ATP sensitive potassium
      channel (K+(ATP) channel) opener/nitric oxide donor) with those of isosorbide
      dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients
      with acute myocardial infarction (AMI) who had undergone reperfusion treatment by
      direct balloon angioplasty. DESIGN: Double blind randomised study. PATIENTS: 60
      patients with AMI in Killip class I. INTERVENTIONS: Patients were assigned into
      two treatment groups: a nicorandil group (n = 30) and an ISDN group (n = 30).
      Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission
      and was administered directly to the treated coronary artery immediately after
      angioplasty. RESULTS: Compared with ISDN, nicorandil more frequently caused
      recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the
      nicorandil group v 5 of 26 (19.2%) in the ISDN group, p = 0.006). The nicorandil
      group had higher values of averaged peak velocity 40 minutes after reperfusion
      (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p = 0.045) and higher values of
      regional wall motion of the infarcted area three weeks after onset of AMI (-1.78
      (1.11) v -2.50 (1.04) SD/chord, p = 0.046). CONCLUSIONS: A combination of
      nicorandil drip infusion starting before reperfusion and intracoronary injection
      immediately after reperfusion is more effective than a similarly performed
      infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI
      area. The nicorandil regimen resulted in better left ventricular regional wall
      motion.

PMID- 14729794
TI  - Percutaneous closure of patent foramen ovale: impact of device design on safety
      and efficacy.
AB  - OBJECTIVE: To compare the safety and efficacy of percutaneous closure of patent
      foramen ovale (PFO) with the Amplatzer PFO occluder (Amplatzer) or the PFO STAR
      device (STAR) in patients with presumed paradoxical embolism. METHODS:
      Implantation characteristics, procedural complications, residual shunt, and
      recurrence of thromboembolic events were recorded prospectively in 100
      consecutive patients undergoing percutaneous PFO closure with the STAR (n = 50)
      or Amplatzer (n = 50) devices between 1998 and 2001. The study was not
      randomised. Device implantation was successful in all cases. RESULTS: There were
      more procedural complications in the STAR than in the Amplatzer group (8/50 v
      1/50, p = 0.01). More than one device placement attempt was an independent
      predictor of procedural complications (odds ratio (OR) 8.5, 95% confidence
      interval (CI) 1.3 to 55.8; p = 0.03). A residual shunt six months after PFO
      closure, assessed by transoesophageal contrast echocardiography, occurred more
      often in the STAR than the Amplatzer group (17/50 v 3/50, p = 0.004), and was
      predicted in the STAR group by the use of a device with a 5 mm as opposed to a 3
      mm disc connector (OR 6.1, 95% CI 1.1 to 34.0; p = 0.04). The actuarial risk of
      recurrent thromboembolic events after 3.5 years was 16.8% (95% CI 7.6% to 34.6%)
      in the STAR and 2.7% (95% CI 0.4% to 17.7%) in the Amplatzer group after three
      years (p = 0.08). CONCLUSIONS: Percutaneous PFO closure with the Amplatzer PFO
      occluder had fewer procedural complications and was more likely to be complete
      than with the STAR device. These findings underline the importance of device
      design for successful percutaneous PFO closure.

PMID- 14729796
TI  - Acute aortic dissection induced renovascular hypertension.

PMID- 14729795
TI  - Improved early ventricular performance with a right ventricle to pulmonary artery
      conduit in stage 1 palliation for hypoplastic left heart syndrome: evidence from
      strain Doppler echocardiography.
AB  - OBJECTIVE: To quantify non-invasively right ventricular (RV) performance in
      infants after stage 1 palliation for hypoplastic left heart syndrome (HLHS).
      DESIGN: Prospective, observational study with two dimensional and strain Doppler
      echocardiography. SETTING: Single tertiary paediatric cardiology centre.
      PATIENTS: Convenience sample of nine consecutive infants with HLHS. Four whose
      surgery involved a systemic to pulmonary artery (S-PA) shunt were compared with
      five whose surgery incorporated a right ventricle to pulmonary artery (RV-PA)
      conduit. METHODS: Basal RV free wall longitudinal strain rate, systolic strain
      (epsilon), and RV percentage area change were calculated during a single
      assessment between 27-50 days after surgery. RESULTS: Cardiopulmonary bypass time
      was longer in patients who underwent RV-PA (226 (30) minutes v 181 (18) minutes,
      p = 0.03), but cross clamp time, duration of ventilation, and inotrope use did
      not differ. Two patients in the S-PA group died, on days 29 and 60 after surgery.
      Peak systolic strain rate (-1.24 (0.19)/s v -0.91 (0.21)/s, p = 0.048), peak
      epsilon (-17.8 (1.8)% v -13.4 (2.0)%, p = 0.01), and RV percentage area change
      (56 (6)% v 25 (6)%, p < 0.01) were all greater among RV-PA patients. These
      indices also tended to be greater in survivors as a group. Ventricular loading
      conditions (oxygen saturations, diuretic treatment, and blood pressure) were
      similar in both groups. CONCLUSION: Strain Doppler echocardiography shows
      improved RV longitudinal systolic contractility in patients during convalescence
      after the RV-PA modification of stage 1 palliation for HLHS compared with those
      with an S-PA shunt.

PMID- 14729797
TI  - Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a
      porcine coronary model.
AB  - OBJECTIVE: To evaluate the effect of stent based methotrexate delivery on
      neointimal hyperplasia. METHODS: Stainless steel coronary stents and biological
      polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs
      with a stent to artery ratio of 1.1:1. The pigs were killed after five days (10
      stents) or four weeks (20 stents). Second, stainless steel coronary stents were
      dip coated in a 10 mg/ml methotrexate-SAE polymer solution, resulting in a total
      load of 150 microg methotrexate/stent. SAE coated stents and methotrexate loaded
      stents were randomly implanted in porcine coronary arteries with a stent to
      artery ratio of 1.2:1 and followed up to four weeks. RESULTS: SAE coated stents
      and bare stents elicited a similar tissue response at five days. At four weeks,
      neointimal hyperplasia induced by the coated stents was less pronounced than with
      the bare stents (1.32 (0.66) v 1.73 (0.93) mm2, p > 0.05). In vitro drug release
      studies showed that 50% of the methotrexate was released in 24 hours, and all
      drug was released within four weeks. No impact on vascular smooth muscle cell
      proliferation or viability was observed in in vitro cell cultures. At four weeks
      the arteries with methotrexate loaded stents had decreased peristrut inflammation
      and neointimal hyperplasia (1.22 (0.34) v 2.25 (1.28) mm2, p < 0.01).
      CONCLUSIONS: SAE coating had an excellent biocompatibility with vascular tissue.
      Stent based delivery of methotrexate in the SAE coating effectively reduced
      neointimal hyperplasia in a porcine coronary stent model, potentially due to
      reduced peristrut inflammation.

PMID- 14729798
TI  - The forces generated within the musculature of the left ventricular wall.
AB  - OBJECTIVES: To test the hypothesis that two populations of myocardial fibres
      fibres aligned parallel to the surfaces of the wall and an additional population
      of fibres that extend obliquely through the wall-when working in concert produce
      a dualistic, self stabilising arrangement. METHODS: Assessment of tensile forces
      in the walls of seven porcine hearts by using needle probes. Ventricular diameter
      was measured with microsonometry and the intracavitary pressure through a fluid
      filled catheter. Positive inotropism was induced by dopamine, and negative
      inotropism by thiopental. The preload was raised by volume load and lowered by
      withdrawal of blood. Afterload was increased by inflation of a balloon in the
      aortic root. The anatomical orientation of the fibres was established
      subsequently in histological sections. RESULTS: The forces in the fibres parallel
      to the surface decreased 20-35% during systolic shrinkage of the ventricle,
      during negative inotropism, and during ventricular unloading. They increased 10
      30% on positive inotropic stimulation and with augmentation in preload and
      afterload. The forces in the oblique transmural fibres increased 8-65% during
      systole, on positive inotropic medication, with an increase in afterload and
      during ventricular shrinkage, and decreased 36% on negative inotropic medication.
      There was a delay of up to 147 ms in the drop in activity during relaxation in
      the oblique transmural fibres. CONCLUSION: Although the two populations of
      myocardial fibres are densely interwoven, it is possible to distinguish their
      functions with force probes. The delayed drop in force during relaxation in
      obliquely oriented fibres indicates that they are hindered in their shortening to
      an extent that parallels any increase in mural thickness. The transmural fibres,
      therefore, contribute to stiffening of the ventricular wall and hence to
      confining ventricular compliance.

PMID- 14729799
TI  - Catheter induced multiple spasms in the right iliac artery during a percutaneous
      coronary intervention.

PMID- 14729800
TI  - Obtaining informed consent from patients in the early phase of acute myocardial
      infarction: physicians' experiences and attitudes.

PMID- 14729801
TI  - Novel imaging techniques for the differentiation of a left ventricular mass.

PMID- 14729802
TI  - Altered short term heart rate variability with spinal cord stimulation in chronic
      refractory angina: evidence for the presence of procedure related cardiac
      sympathetic blockade.

PMID- 14729803
TI  - Carer knowledge of children's medical problems in a paediatric cardiology
      outpatient setting.

PMID- 14729805
TI  - Ventilatory response to exercise in patients after correction of cyanotic
      congenital heart disease: relation with clinical outcome after surgery.

PMID- 14729806
TI  - Assessment of depression following acute myocardial infarction using the Beck
      depression inventory.

PMID- 14729807
TI  - Secretion of atrial natriuretic peptide in idiopathic giant atrium.

PMID- 14729808
TI  - Indications for the closure of patent foramen ovale.

PMID- 14729809
TI  - Chronic therapeutically refractory angina pectoris.

PMID- 14729810
TI  - Implantable cardioverter-defibrillator treatment and resynchronisation in heart
      failure.

PMID- 14729812
TI  - Tachycardiomyopathy: a diagnosis not to be missed.
AB  - The prognosis of dilated cardiomyopathy is generally poor. In the vast majority
      of cases the cause of the ventricular dysfunction is irreversible but
      occasionally potentially curable causes are identified. Tachycardiomyopathy is a
      rare and potentially treatable cause of heart failure. A patient with a
      particularly severe case who had an excellent outcome is presented.

PMID- 14729813
TI  - Computed tomographic virtual cardioscopy in a case of left atrial myxoma.
AB  - Computed tomographic virtual cardioscopy was used to provide clear and precise
      visualisation of a myxoma with a stalk arising from the interatrial septum. This
      technique permits the safe, reliable, and non-invasive diagnosis of intracardiac
      lesions. This case is presented to assist the cardiovascular surgeon in
      preoperative planning or in developing a simulation of robotic cardiac surgery.

PMID- 14729814
TI  - Rare case of heart failure caused by compression of the left atrium by a thoracic
      aortic aneurysm.
AB  - A 61 year old patient was found to have an aneurysm extending from the aortic
      root to the suprarenal region. He underwent first stage surgery with aortic root
      and arch replacement, prosthetic aortic valve replacement, and coronary artery
      bypass grafting. Four weeks later, he presented with breathlessness and signs of
      heart failure and pleural effusion. Computed tomography showed that the left
      atrium was compressed between the aortic aneurysm posteriorly and the left
      ventricle and sternum anteriorly. Obstruction of the superior vena cava,
      bronchus, oesophagus, and rarely right atrium by an aortic aneurysm has been
      described before but presentation with left atrial compression has not been
      reported.

PMID- 14729815
TI  - Masquerade: a malignant arrhythmia masquerading as benign.
AB  - Pseudoatrial flutter has been reported to have benign causes, but this is the
      first report of a malignant arrhythmia presenting as a benign arrhythmia. An 82
      year old patient presented with ventricular tachycardia and electrical artefact
      appearing as atrial flutter. In this case, comparing the morphology of the QRS
      complexes in the rhythm strip with those in lead II showed the arrhythmia to be
      ventricular in origin and points to the importance of comparing all leads of the
      ECG before arriving at a diagnosis.

PMID- 14729816
TI  - BRCA1 functions as a breast stem cell regulator.
AB  - BRCA1 is an important susceptibility gene for breast cancer, which confers
      substantial lifetime risks of breast cancer, particularly in the pre-menopausal
      age group. Typically, carriers of BRCA1 mutations develop breast tumours that
      grow rapidly and are high grade and oestrogen receptor negative. They also
      possess a basal epithelial phenotype, as defined by cytokeratin expression, that
      is not present in most breast cancers. It has recently been proposed that the
      adult breast stem cell expresses only basal keratins. Others have indicated a
      CD44 positive, CD24 negative phenotype for breast cancer stem cells. In this
      paper, I argue that the biology of human BRCA1 and its rodent homologues and the
      clinicopathological features of breast cancer related to BRCA1 support the notion
      that one of the key functions of BRCA1 is to act as a stem cell regulator. This
      has implications for the management of carriers of mutations of BRCA1, in part
      because support for the role of BRCA1 as a stem cell regulator would emphasise
      the distinct nature of breast cancer related to BRCA1.

PMID- 14729819
TI  - A novel locus for autosomal dominant non-syndromic hearing loss, DFNA31, maps to
      chromosome 6p21.3.
AB  - BACKGROUND: Non-syndromic hearing loss is the most genetically heterogeneous
      trait known in humans. To date, 51 loci for autosomal dominant non-syndromic
      sensorineural hearing loss (NSSHL) have been identified by linkage analysis.
      OBJECTIVE: To investigate the genes involved in a Dutch family with NSSHL.
      METHODS: Linkage analysis in a large Dutch pedigree with progressive bilateral
      loss of the mid and high frequencies, in which a novel dominant locus for
      postlingual NSSHL (DFNA31) has been identified. RESULTS: DFNA31 was found to be
      located in a 7.5 cM region of chromosome 6p21.3 between D6S276 (telomeric) and
      D6S273 (centromeric), with a maximum two point LOD score of 5.99 for D6S1624. DNA
      sequencing of coding regions and exon/intron boundaries of two candidate genes
      (POU5F1, GABBR1) in this interval did not reveal disease causing mutations.
      CONCLUSIONS: Haplotype analysis indicated that the genetic defect in this family
      does not overlap the DFNA13 and DFNA21 regions that are also located on 6p.
      Identification of the disease gene will be of major importance in understanding
      the pathophysiology of hearing impairment.

PMID- 14729820
TI  - Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.
AB  - Respiratory chain complex I deficiency represents a genetically heterogeneous
      group of diseases resulting from mutations in mitochondrial or nuclear genes.
      Mutations have been reported in 13 of the 14 subunits encoding the core of
      complex I (seven mitochondrial and six nuclear genes) and these result in Leigh
      or Leigh-like syndromes or cardiomyopathy. In this study, a combination of
      denaturing high performance liquid chromatography and sequence analysis was used
      to study the NDUFS3 gene in a series of complex I deficient patients. Mutations
      found in this gene (NADH dehydrogenase iron-sulphur protein 3), coding for the
      seventh and last subunit of complex I core, were shown to cause late onset Leigh
      syndrome, optic atrophy, and complex I deficiency. A biochemical diagnosis of
      complex I deficiency on cultured amniocytes from a later pregnancy was confirmed
      through the identification of disease causing NDUFS3 mutations in these cells.
      While mutations in the NDUFS3 gene thus result in Leigh syndrome, a dissimilar
      clinical phenotype is observed in mutations in the NDUFV2 and NDUFS2 genes,
      resulting in encephalomyopathy and cardiomyopathy. The reasons for these
      differences are uncertain.

PMID- 14729817
TI  - The 16189 variant of mitochondrial DNA occurs more frequently in C282Y
      homozygotes with haemochromatosis than those without iron loading.
AB  - BACKGROUND: Patients with hereditary haemochromatosis (HH) are usually homozygous
      for the C282Y mutation in the HFE gene. They have variable expression of iron
      overload and present with a variety of complications, including liver disease,
      diabetes, arthropathy, fatigue, and cardiomyopathy. The mitochondrial 16189
      variant is associated with diabetes, dilated cardiomyopathy, and low body fat at
      birth, and might contribute to genetic predisposition in further multifactorial
      disorders. The objective of this study was to determine the frequency of the
      16189 variant in a range of patients with haemochromatosis, who had mutations in
      the HFE gene. METHODS: Blood DNA was analysed for the presence of the 16189
      variant in British, French, and Australian C282Y homozygotes and controls, with
      known iron status, and in birth cohorts. RESULTS: The frequency of the
      mitochondrial 16189 variant was found to be elevated in individuals with
      haemochromatosis who were homozygous for the C282Y allele, compared with
      population controls and with C282Y homozygotes who were asymptomatic (42/292
      (14.4%); 102/1186 (8.6%) (p = 0.003); and 2/64 (3.1%) (p = 0.023), respectively).
      CONCLUSIONS: Iron loading in C282Y homozygotes with HH was exacerbated by the
      presence of the mitochondrial 16189 variant.

PMID- 14729822
TI  - Screening for genomic rearrangements of the MMR genes must be included in the
      routine diagnosis of HNPCC.

PMID- 14729824
TI  - Common apolipoprotein E polymorphisms and risk of clinical malaria in the Gambia.

PMID- 14729826
TI  - Refining the phenotype of common mutations in Rett syndrome.

PMID- 14729827
TI  - A case control and family based association study of the neuregulin1 gene and
      schizophrenia.

PMID- 14729831
TI  - A locus on 15q15-15qter influences dyslexia: further support from a
      transmission/disequilibrium study in an Italian speaking population.

PMID- 14729829
TI  - Mental retardation and cardiovascular malformations in NF1 microdeleted patients
      point to candidate genes in 17q11.2.

PMID- 14729833
TI  - Congo red, doxycycline, and HSP70 overexpression reduce aggregate formation and
      cell death in cell models of oculopharyngeal muscular dystrophy.

PMID- 14729835
TI  - Missense mutations in the beta strands of the single A-domain of matrilin-3
      result in multiple epiphyseal dysplasia.

PMID- 14729836
TI  - Expression of Gja1 correlates with the phenotype observed in oculodentodigital
      syndrome/type III syndactyly.

PMID- 14729838
TI  - TBX22 mutations are a frequent cause of cleft palate.

PMID- 14729841
TI  - Isolated Robin sequence associated with a balanced t(2;17) chromosomal
      translocation.

PMID- 14729840
TI  - Identification of COL2A1 mutations in platyspondylic skeletal dysplasia, Torrance
      type.

PMID- 14729842
TI  - Linkage mapping of systemic lupus erythematosus (SLE) in Finnish families
      multiply affected by SLE.

PMID- 14729843
TI  - Induction of instability of normal length trinucleotide repeats within human
      disease genes.

PMID- 14729844
TI  - Epigenetic abnormalities of the mannose-6-phosphate/IGF2 receptor gene are
      uncommon in human overgrowth syndromes.

PMID- 14729845
TI  - Genetic correlation between plasma levels of C4BP isoforms containing beta chains
      and susceptibility to thrombosis.

PMID- 14729846
TI  - Founder mutations of CYP1B1 gene in patients with congenital glaucoma from the
      United States and Brazil.

PMID- 14729847
TI  - No evidence of an association between the T16189C mtDNA variant and late onset
      dementia.

PMID- 14729848
TI  - Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient
      founder mutation or arises from multiple founders.

PMID- 14729849
TI  - A novel COCH mutation, V104del, impairs folding of the LCCL domain of cochlin and
      causes progressive hearing loss.

PMID- 14729850
TI  - Clinical and genetic characteristics of alpha cardiac actin gene mutations in
      hypertrophic cardiomyopathy.

PMID- 14729851
TI  - Novel germline mutations in the adenomatous polyposis coli gene in Polish
      families with familial adenomatous polyposis.

PMID- 14729852
TI  - Very low penetrance in 85 Japanese families with facioscapulohumeral muscular
      dystrophy 1A.

PMID- 14729853
TI  - Improved method for making nondenaturing composite gradient gels for the
      electrophoretic separation of lipoproteins.
AB  - Nondenaturing gradient gel electrophoresis continues to be used widely for
      resolution and characterization of lipoprotein subclasses. Methods for making
      such gels in the laboratory have been published, but occasionally samples do not
      display uniform mobilities for all lanes in a laboratory-made gel. To help
      overcome this limitation, we recommend a modification

PMID- 14729854
TI  - Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance
      liquid chromatography-mass spectrometry.
AB  - 24S-Hydroxycholesterol (24S-OH-Chol) and 27-hydroxycholesterol (27-OH-Chol) are
      oxidized derivatives of cholesterol and of potential diagnostic interest because
      their circulating levels may reflect the cholesterol metabolism of the brain and
      macrophages, respectively. We developed a sensitive and specific HPLC-MS method
      for the quantification of 24S-OH-Chol and 27-OH-Chol in human plasma. In contrast
      to currently available procedures based on gas chromatography-mass spectrometry,
      this methodology offers the advantage that no time-consuming derivatization is
      needed. After saponification, solid-phase extraction, and HPLC separation under
      reversed-phase column conditions, detection by MS was performed using atmospheric
      pressure chemical ionization and selected ion monitoring mode. The standard
      curves were linear throughout the calibration range for both oxysterols. Within
      day and between-day coefficients of variation were less than 9%, and the
      recoveries ranged between 98% and 103%. The quantification limits were 40 and 25
      microg/l for 24S-OH-Chol and 27-OH-Chol, respectively. Mean values for both
      oxysterols were determined in plasma from 22 healthy volunteers. The sensitive
      and selective HPLC-MS method described here combined with the appropriate workup
      procedure allow the quantification of 24S-OH-Chol and 27-OH-Chol in plasma
      samples, for example in clinical studies to elaborate the clinical usefulness of
      these two oxysterols.

PMID- 14729855
TI  - Potential involvement of dissociated apoA-I in the ABCA1-dependent cellular lipid
      release by HDL.
AB  - Helical apolipoproteins of high density lipoprotein (HDL) remove phospholipid and
      cholesterol from cells and generate HDL particles being mediated by ATP binding
      cassette transporter A1 (ABCA1). In murine macrophage cell line RAW264 cells,
      cAMP induced expression of ABCA1, release of cellular phospholipid and
      cholesterol by apolipoprotein A-I (apoA-I), and reversible binding of apoA-I to
      the cell. The apoA-I-dependent lipid release was directly proportional to the
      cAMP-induced binding of apoA-I, and was inhibited 70% by a monoclonal antibody
      selective to lipid-free apoA-I, 725-1E2. In contrast, apparent cellular
      cholesterol release to HDL was substantial even without ABCA1 induction, and it
      was increased only by 27% after the cAMP treatment. The antibody inhibited this
      increment by 70%. Lipid-free apoA-II liberated apoA-I from HDL by displacement
      and thereby markedly expanded the cAMP-induced part of the cholesterol release to
      the HDL-containing medium, and the antibody inhibited this part also by 70%.
      Binding experiments of the double-labeled reconstituted HDL showed that cAMP
      induced reversible binding of apoA-I but not the association of cholesteryl ester
      with the cells. The effect of the antibody on the cellular cholesterol release to
      the reconstituted HDL was similar to that of the HDL-mediated release. The data
      implicated that the ABCA1-dependent cholesterol release to HDL is mediated by
      apoA-I dissociated from HDL.

PMID- 14729856
TI  - Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma
      lipids and diabetes risk in an Asian population.
AB  - We investigated the association of C1431T and Pro12Ala polymorphisms at the
      peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma
      lipids and insulin resistance-related variables, according to diabetes status, in
      a large and representative Asian population from Singapore consisting of 2,730
      Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk
      and examined gene-nutrient interactions between these variants and the ratio of
      polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index
      (BMI) and fasting insulin. We found differential effects of these gene variants.
      The Pro12Ala polymorphism was more associated with plasma lipids and fasting
      glucose concentrations, whereas the C1431T polymorphism was related to the risk
      of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did
      Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting
      glucose was modified by diabetes status (P < 0.001). After controlling for
      confounders, carriers of the T allele had decreased risk of diabetes compared
      with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58
      0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92;
      P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent
      allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these
      polymorphisms on BMI or insulin.

PMID- 14729857
TI  - Quantitative analysis of the expression of ACAT genes in human tissues by real
      time PCR.
AB  - ACAT (also called sterol o-acyltransferase) catalyzes the esterification of
      cholesterol by reaction with long-chain acyl-CoA derivatives and plays a pivotal
      role in the regulation of cholesterol homeostasis. Although two human ACAT genes
      termed ACAT-1 and ACAT-2 have been reported, prior research on differential
      tissue expression is qualitative and incomplete. We have developed a quantitative
      multiplex assay for each ACAT isoform after RT treatment of total RNA using
      TaqMan real-time quantitative PCR normalized to beta-actin in the same reaction
      tube. This enabled us to calculate the relative abundance of transcripts in
      several human tissues as an ACAT-2/ACAT-1 ratio. In liver (n = 17), ACAT-1
      transcripts were on average 9-fold (range, 1.7- to 167-fold) more abundant than
      ACAT-2, whereas in duodenal samples (n = 10), ACAT-2 transcripts were on average
      3-fold (range, 0.39- to 12.2-fold) more abundant than ACAT-1. ACAT-2 was detected
      for the first time in peripheral blood mononuclear cells. Interesting differences
      in ACAT-2 mRNA expression were evident in subgroup analysis of samples from
      different sources. These results demonstrate quantitatively that ACAT-1
      transcripts predominate in human liver and ACAT-2 transcripts predominate in
      human duodenum and support the notion that ACAT-2 has an important regulatory
      role in liver and intestine.

PMID- 14729858
TI  - Phosphomevalonate kinase is a cytosolic protein in humans.
AB  - In the past decade, a predominant peroxisomal localization has been reported for
      several enzymes functioning in the presqualene segment of the
      cholesterol/isoprenoid biosynthesis pathway. More recently, however, conflicting
      results have been reported raising doubts about the postulated role of
      peroxisomes in isoprenoid biosynthesis, at least in humans. In this study, we
      have determined the subcellular localization of human phosphomevalonate kinase
      using a variety of biochemical and microscopic techniques, including conventional
      subcellular fractionation studies, digitonin permeabilization studies,
      immunofluorescence, and immunoelectron microscopy. We found an exclusive
      cytosolic localization of both endogenously expressed human phosphomevalonate
      kinase (in human fibroblasts, human liver, and HEK293 cells) and overexpressed
      human phosphomevalonate kinase (in human fibroblasts, HEK293 cells, and CV1
      cells). No indication of a peroxisomal localization was obtained. Our results do
      not support a central role of peroxisomes in isoprenoid biosynthesis.

PMID- 14729859
TI  - Protein-bound 4-hydroxy-2-hexenal as a marker of oxidized n-3 polyunsaturated
      fatty acids.
AB  - In the present study, to investigate the contribution of n-3 PUFAs in the
      oxidative modification of protein in vivo, we characterize the covalent binding
      of 4-hydroxy-2-hexenal (HHE), a potent cytotoxic aldehyde originating from the
      peroxidation of n-3 PUFAs, to protein and describe the production of this
      aldehyde in oxidatively modified LDL and in human atherosclerotic lesions. Upon
      incubation with BSA, HHE was rapidly incorporated into the protein and generated
      the protein-linked carbonyl derivative, a potential marker of oxidatively
      modified proteins under oxidative stress. To detect the protein-bound HHE in
      vivo, we raised monoclonal antibody HHE53 (MAb HHE53) directed to the HHE
      modified protein and identified the Michael addition-type HHE-histidine adduct as
      the major epitope. This antibody reacted with copper-oxidized LDL, suggesting
      that HHE was produced during the oxidative modification of LDL. In addition, we
      demonstrated that the materials immunoreactive to MAb HHE53 indeed constituted
      the atherosclerotic lesions, in which intense positivity was associated primarily
      with macrophage-derived foam cells. The results of this study suggest that the
      reaction between oxidized n-3 PUFAs and protein might represent a process common
      to the formation of degenerative proteins during aging and its related diseases.

PMID- 14729860
TI  - ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI
      and CD36.
AB  - The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding
      specificity. SR-BI is well characterized as a HDL receptor that mediates
      selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL,
      also binds HDL and mediates selective cholesteryl ester uptake, although much
      less efficiently than SR-BI. Apolipoprotein A-II (apoA-II), the second most
      abundant HDL protein, is considered to be proatherogenic, but the underlying
      mechanisms are unclear. We previously showed that apoA-II modulates SR-BI
      dependent binding and selective uptake of cholesteryl ester from reconstituted
      HDL. To investigate the effect of apoA-II in naturally occurring HDL on these
      processes, we compared HDL without apoA-II (from apoA-II null mice) with HDLs
      containing differing amounts of apoA-II (from C57BL/6 mice and transgenic mice
      expressing a mouse apoA-II transgene). The level of apoA-II in HDL was inversely
      correlated with HDL binding and selective cholesteryl ester uptake by both
      scavenger receptors, particularly CD36. Interestingly, for HDL lacking apoA-II,
      the efficiency with which CD36 mediated selective uptake reached a level similar
      to that of SR-BI. These results demonstrate that apoA-II exerts a marked effect
      on HDL binding and selective lipid uptake by the class B scavenger receptors and
      establishes a potentially important relationship between apoA-II and CD36.

PMID- 14729861
TI  - Prebeta high density lipoprotein has two metabolic fates in human apolipoprotein
      A-I transgenic mice.
AB  - We compared the in vivo metabolism of prebeta HDL particles isolated by anti
      human apolipoprotein A-I (apoA-I) immunoaffinity chromatography (LpA-I) in human
      apoA-I transgenic (hA-I Tg) mice with that of lipid-free apoA-I (LFA-I) and small
      LpA-I. After injection, prebeta LpA-I were removed from plasma more rapidly than
      were LFA-I and small LpA-I. Prebeta LpA-I and LFA-I were preferentially degraded
      by kidney compared with liver; small LpA-I were preferentially degraded by the
      liver. Five minutes after tracer injection, 99% of LFA-I in plasma was found to
      be associated with medium-sized (8.6 nm) HDL, whereas only 37% of prebeta tracer
      remodeled to medium-sized HDL. Injection of prebeta LpA-I doses into C57Bl/6
      recipients resulted in a slower plasma decay compared with hA-I Tg recipients and
      a greater proportion (>60%) of the prebeta radiolabel that was associated with
      medium-sized HDL. Prebeta LpA-I contained one to four molecules of
      phosphatidylcholine per molecule of apoA-I, whereas LFA-I contained less than
      one. We conclude that prebeta LpA-I has two metabolic fates in vivo, rapid
      removal from plasma and catabolism by kidney or remodeling to medium-sized HDL,
      which we hypothesize is determined by the amount of lipid associated with the
      prebeta particle and the particle's ability to bind to medium-sized HDL.

PMID- 14729862
TI  - Sarcolemmal FAT/CD36 in human skeletal muscle colocalizes with caveolin-3 and is
      more abundant in type 1 than in type 2 fibers.
AB  - FAT/CD36 is a transmembrane protein that is thought to facilitate cellular long
      chain fatty acid uptake. However, surprisingly little is known about the
      localization of FAT/CD36 in human skeletal muscle. By confocal immunofluorescence
      microscopy, we demonstrate high FAT/CD36 expression in endothelial cells and
      weaker but significant FAT/CD36 expression in sarcolemma in human skeletal
      muscle. No apparent intracellular staining was observed in the muscle cells.
      There are indications in the literature that caveolae may be involved in the
      uptake of fatty acids, possibly as regulators of FAT/CD36 or other fatty acid
      transporters. We show that in sarcolemma, FAT/CD36 colocalizes with the muscle
      specific caveolae marker protein caveolin-3, suggesting that caveolae may
      regulate cellular fatty acid uptake by FAT/CD36. Furthermore, we provide evidence
      that FAT/CD36 expression is significantly higher in type 1 compared with type 2
      fibers, whereas caveolin-3 expression is significantly higher in type 2 fibers
      than in type 1 fibers.

PMID- 14729863
TI  - APOA5 gene variants, lipoprotein particle distribution, and progression of
      coronary heart disease: results from the LOCAT study.
AB  - Animal and human studies support a role for apolipoprotein A-V (apoA-V) in
      triglyceride (TG) metabolism. We examined the relationship of APOA5 -1131T>C and
      S19W with lipid subfractions and progression of atherosclerosis in the Lopid
      Coronary Angiography Trial. Compared with -1131TT men (n = 242), carriers of the 
      1131C allele (n = 54) had significantly higher total TG (P = 0.03), reflected in
      significantly increased VLDL mass [higher VLDL-TG, VLDL-cholesterol, VLDL
      protein, and surface lipids (all P < 0.05)]. Because apoB levels were unaffected
      by genotype, this suggests an increase in VLDL size and not number. Compared with
      19SS men (n = 268), 19W carriers (n = 44) had higher intermediate density
      lipoprotein (IDL)-TG, IDL-cholesterol (P = 0.04), and IDL-surface components
      [free cholesterol (P = 0.005) and phospholipids (P = 0.017)] but not protein
      content, suggesting an increase in IDL lipid enrichment resulting in an increase
      in IDL size. 19W carriers also showed a trend toward increased progression of
      atherogenesis, as measured by change in average diameter of segments (-0.46 +/-
      0.011 mm compared with -0.016 +/- 0.006 mm) in 19SS men (P = 0.08). There was no
      effect of genotype on the response of these parameters to gemfibrozil treatment.
      These results shed new light on the role of APOA5 variants in TG metabolism and
      coronary heart disease risk.

PMID- 14729864
TI  - Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC
      with tandem mass spectrometry.
AB  - We investigated the formation of PGF(2alpha) 1-ethanolamide, PGE(2) 1
      ethanolamide, and PGD(2) 1-ethanolamide (prostamides F(2alpha), E(2), and D(2),
      respectively) in liver, lung, kidney, and small intestine after a single
      intravenous bolus administration of 50 mg/kg of anandamide to normal and fatty
      acid amide hydrolase knockout (FAAH -/-) male mice. One group of three normal
      mice was not dosed (naive) while another group of three normal mice received a
      bolus intravenous injection of 50 mg/kg of anandamide. Three FAAH -/- mice also
      received an intravenous injection of 50 mg/kg of anandamide. After 30 min, the
      lung, liver, kidney, and small intestine were harvested and processed by liquid
      liquid extraction. The concentrations of prostamide F(2alpha), prostamide E(2),
      prostamide D(2), and anandamide were determined by HPLC-tandem mass spectrometry.
      Prostamide F(2alpha) was detected in tissues in FAAH -/- mice after
      administration of anandamide. Concentrations of anandamide, prostamide E(2), and
      prostamide D(2) in liver, kidney, lung, and small intestine were much higher in
      the anandamide-treated FAAH -/- mice than those of the anandamide-treated control
      mice. This report demonstrates that prostamides, including prostamide F(2alpha),
      were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway
      when the competing FAAH pathway is lacking.

PMID- 14729865
TI  - Detection of PrPsc on lymphoid tissues from naturally affected scrapie animals:
      comparison of three visualization systems.
AB  - We assessed three different visualization systems used routinely in research and
      diagnosis of transmissable spongiform encephalopathies (TSEs) to demonstrate
      whether the methodology applied to immunohistochemical (IHC) examination may
      alter the results concerning detection of prion protein (PrPsc) in the
      lymphoreticular system (LRS): avidin-biotin-peroxidase (Vectastain ABC kit;
      Vector), Envision (DAKO), and catalyzed signal amplification (CSA; DAKO). The
      study aimed to determine which of these showed the highest sensitivity, with the
      hope of providing an accurate tool for pathogenesis and preclinical diagnosis
      research in TSEs. Histological sections from palatine tonsils, spleen, GALT
      (ileum and ileocecal valve), and lymph nodes from sheep belonging to a Spanish
      scrapie-positive flock were processed by IHC using L42 as primary antibody. As
      substrate chromogen, diaminobenzidine was used, and all slides were subjectively
      assessed by light microscopy. A further study using an image analyzer software
      system was carried out to confirm that the conclusion provided by microscopic
      examination was objective. The CSA system showed the highest sensitivity in all
      cases, increasing both variables assessed: the number of follicles that were
      PrPsc-positive was detected as well as the intensity of immunostaining in each of
      them.

PMID- 14729866
TI  - Laminins alpha2 and alpha4 in pancreatic acinar basement membranes are required
      for basal receptor localization.
AB  - Basement membranes (BMs) are thin layers of extracellular matrix (ECM) found at
      the basal surface of many cell types, including epithelial cells. BMs present
      growth, differentiation, and anti-apoptotic signals and provide structural
      support to cells, compartmentalize tissues, and serve as filters. The structure
      and function of BMs depend on their complement of laminins, a family of alpha
      beta gamma heterotrimeric glycoproteins. We found that laminins containing the
      alpha2 and alpha4 chains are the major laminins in pancreatic acinar BMs.
      Importantly, these laminins were required for proper basal localization on acinar
      cells of two laminin receptors, dystroglycan and integrin alpha6beta4 .

PMID- 14729867
TI  - Temporal changes in PTHrP, Bcl-2, Bax, caspase, TGF-beta, and FGF-2 expression
      following growth plate irradiation with or without radioprotectant.
AB  - This study examined temporal changes in growth plate apoptosis molecules and
      growth factors in an animal model of radiation injury with and without a
      radioprotectant. Thirty weanling 5-week Sprague-Dawley rats underwent right knee
      irradiation with single-fraction 17.5 Gy while the left served as internal
      control. Six animals each were sacrificed at 0.5, 1, 2, 3, or 4 weeks after
      irradiation. Half of the animals received pretreatment with amifostine (WR-2721)
      radioprotectant. Immunohistochemical staining for PTHrP, Bcl-2, Bax, caspase-3,
      FGF-2, and TGF-beta was performed. PTHrP decreased to a nadir at 1 week after
      irradiation but rebounded to above control levels at 2 weeks in the reserve and
      transitional zones. The radioprotectant amifostine blunted the decrease in PTHrP
      but kept PTHrP expression lower than controls during the rebound phase in
      untreated irradiated animals. Hypertrophic zone Bax expression was decreased by
      amifostine in both irradiated and non-irradiated limbs at 1 and 2 weeks. FGF, TGF
      beta, Bcl-2, and caspase levels generally decreased at 1 week and returned
      thereafter toward control levels. These findings underscore the importance of
      PTHrP in response to growth plate irradiation and show the novel finding of a
      decrease in Bax expression with amifostine pretreatment.

PMID- 14729868
TI  - Cocaine- and amphetamine-regulated transcript (CART) is expressed in several
      islet cell types during rat development.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide
      widely expressed in the central and peripheral, including the enteric, nervous
      systems. CART is also expressed in pituitary endocrine cells, adrenomedullary
      cells, islet somatostatin cells, and in rat antral gastrin cells. We used
      immunocytochemistry (IHC) and in situ hybridization (ISH) to study CART
      expression in developing rat pancreas. We also examined co-expression of CART and
      islet hormones and developmental markers and the effect of CART on proliferation
      using clonal insulin cells (INS-1 832/13). A major portion of each of the islet
      cell types, except the ghrelin cells, expressed CART during a period before and
      around birth. Two weeks postnatally, CART expression was restricted to
      somatostatin cells. Pre- and early postnatally, many of the CART-expressing cells
      co-expressed cytokeratin 20 (CK20), a marker of duct cells and islet precursor
      cells, the trophic hormone gastrin, and a smaller subpopulation also harbored the
      proliferation marker Ki67. CART was also expressed in pancreatic nerve fibers,
      both sensory and autonomic, and in ganglion nerve cell bodies. Although highly
      expressed in the developing islets, CART did not affect proliferation of INS-1
      cells. We have demonstrated that CART is expressed in several islet cell types
      during rat development but is restricted to somatostatin cells and neurons in the
      adult rat.

PMID- 14729869
TI  - Frequency of M-cadherin-stained satellite cells declines in human muscles during
      aging.
AB  - To answer the question of whether the satellite cell pool in human muscle is
      reduced during aging, we detected satellite cells in 30- microm-thick transverse
      sections under the confocal microscope by binding of M-cadherin antibody. The
      basal lamina was detected with laminin. Nuclei were stained with bisbenzimide or
      propidium iodide. Satellite cells were counted by applying the disector method
      and unbiased sampling design. To determine if there are age-related differences
      in muscle fiber types, morphometric characteristics of muscle fibers were
      examined on thin sections stained for myofibrillar ATPase. Autopsy samples of
      vastus lateralis muscle from six young (28.7 +/- 2.3 years) and six old (70.8 +/-
      1.3 years) persons who had suffered sudden death were analyzed. Numbers of
      satellite cells per fiber length (Nsc/Lfib) and number of satellite cells per
      total number of nuclei (satellite cell nuclei + myonuclei) (Nsc/Nnucl) were
      significantly lower in the old group (p < 0.05). We demonstrate the importance of
      proper sampling and counting in estimation of sparsely distributed structures
      such as satellite cells. Our results support the hypothesis that the satellite
      cell fraction declines during aging.

PMID- 14729870
TI  - Apoptosis in the epididymal epithelium of adult male golden hamster exposed to
      diethylstilbestrol.
AB  - Apoptosis in the testis and prostate exposed to disrupters of endocrine function,
      including diethylstilbestrol (DES), during neonatal or postnatal periods has
      repeatedly been demonstrated, but not in the mature epididymis. We investigated
      the effects of DES, a potent and synthetic estrogen, on apoptosis in the adult.
      Adult male golden hamsters received an SC injection of DES and were then
      sacrificed to collect epididymides after 1, 4, or 7 days of treatment. A
      significant decrease in epididymal weight and an increase in apoptotic cells were
      shown on the first day after DES injection. Flow cytometry showed that DES
      treatment (1 mg/kg) for 1, 4, or 7 days induced significant apoptosis both in the
      caput and the cauda epididymides. Greater numbers of apoptotic cells were
      detected in the caput than in the cauda at a fixed time after DES treatment.
      Serum levels of testosterone decreased markedly within 24 hr after DES
      administration, reaching undetectable levels of 0.1 ng/ml at 4 days and
      thereafter. These results indicate that DES administration can increase
      epididymal apoptosis with a decrease in serum testosterone levels. Because DES
      used to be injected into domestic animals, adult males also have a chance to take
      this substance through food. Our study indicates that exposure to DES in adults
      is as toxic as that in the perinatal period.

PMID- 14729871
TI  - CFTR localization in native airway cells and cell lines expressing wild-type or
      F508del-CFTR by a panel of different antibodies.
AB  - The intracellular localization of cystic fibrosis transmembrane conductance
      regulator (CFTR) in native tissues is a major issue in the study of mutation,
      processing, and trafficking effects in CFTR and in the evaluation of therapeutic
      strategies in cystic fibrosis (CF). This work evaluated the applicability of ten
      different antibodies (Abs) under various fixation techniques for CFTR
      localization in fresh-brushed nasal epithelial cells collected from CF patients
      homozygous for F508del and control individuals. In parallel, the same Ab panel
      was also tested on BHK cell lines overexpressing wild-type or F508del CFTR. The
      Abs MATG1061, 169, Lis1, MP-CT1, CC24-R, MAB25031, and MAB1660 gave the best
      detection of CFTR in the apical region (AR) of nasal tall columnar epithelial
      (TCE) cells. The labeling pattern of these Abs was consistent with the postulated
      processing defect of F508del CFTR because only a minority of CF TCE cells present
      CFTR in the AR. In contrast, M3A7, MM13-4, and L12B4 weakly react with the AR and
      stain almost exclusively a cis-Golgi-like structure in the majority of CF and non
      CF airway cells. In BHK cells, all the Abs enabled distinction between wild-type
      CFTR localization in cell membrane from F508del CFTR, which in these cells is
      exclusively located in the endoplasmic reticulum.

PMID- 14729872
TI  - A novel technology allowing immunohistochemical staining of a tissue section with
      50 different antibodies in a single experiment.
AB  - Immunohistochemical (IHC) examination is frequently necessary for a histological
      differential diagnosis of tumors. To simplify IHC examination, we have developed
      a novel device called a "multiplex-immunostain chip (MI chip)." The chip is a
      panel of antibodies contained in a silicon rubber plate that consists of 50 2-mm
      diameter wells. A tissue section slide is placed on the plate and is fastened
      tightly with a specially designed clamp. The plate with the slide is then turned
      upside down, which applies the antibodies to the section. This technology allows
      IHC staining of a tissue section with 50 different antibodies in a single
      experiment, reducing the time, effort, and expense of IHC analysis. In addition,
      it enables pathologists to compare expression of multiple antigens on a tissue
      section simply by changing microscopic fields on a single slide. These features
      are unique to the MI chip technology. The method requires no expensive
      instruments. This device can be used in various applications in differential
      diagnosis of tumors and the field of cell biology.

PMID- 14729873
TI  - Silver carbonate staining reveals mitochondrial heterogeneity.
AB  - Silver staining methods, when selective, yield a high-contrast and high
      resolution image in optical microscopy. A classical method for silver
      impregnation of mitochondria has been applied to murine tissues and reveals a
      marked heterogeneity among mitochondria in single cells. This heterogeneity can
      be detected in the optical microscope but is even more evident at the
      ultrastructural level. The differences in staining intensity may reflect
      different stages in the mitochondrial life cycle. The progressive accumulation of
      uranyl-argyrophilic material may be a marker of mitochondrial aging. This highly
      selective staining procedure may be of use in studies of mitochondrial changes
      under pathological conditions and during apoptosis.

PMID- 14729874
TI  - Localization of inhibins and activins in normal endocrine cells and endocrine
      tumors of the gut and pancreas: an immunohistochemical and in situ hybridization
      study.
AB  - Activins and inhibins, which belong to the TGF beta family, are composed of
      different combinations of alpha-, betaA-, and betaB-subunits, resulting in
      inhibin A (alphabetaA), inhibin B (alphabetaB), activin A (betaAbetaA), activin B
      (betaBbetaB), and activin AB (betaAbetaB). They regulate several cell functions,
      acting as paracrine/autocrine factors. Their actions, which depend on binding to
      specific receptors, are also modulated by follistatin. Gastroenteropancreatic
      (GEP) endocrine cells and endocrine tumors (ETs) produce several growth factors,
      but it is not well known whether they express follistatin and the various
      inhibin/activin subunits. We studied their expression in 65 GEP ETs using
      immunohistochemistry (IHC) and in situ hybridization (ISH). The alpha-subunit and
      follistatin were not identified in normal GEP endocrine cells and were poorly
      expressed in ETs. A betaA-subunit immunoreactivity (IR) was detected in A-, G-,
      EC-, and GIP-cells, while betaB-chain IR was present only in D-cells. The mRNAs
      encoding for these molecules were poorly expressed in normal tissues. BetaA- and
      betaB-subunits were identified in several ETs by both IHC and ISH: betaA-subunit
      mainly in G-cell and A-cell ETs, and betaB-subunit in D-cell, A-cell, and EC-cell
      ETs. Our results demonstrate a differential expression of activin/inhibin
      subunits among different types of GEP endocrine cells and related tumors,
      suggesting a role in modulation of biological functions of these normal and
      neoplastic endocrine cells.

PMID- 14729875
TI  - Expression of lipoxygenase during organogenic nodule formation from hop
      internodes.
AB  - Study of lipoxygenase expression (LOX; EC 1.13.11.12) during organogenic nodule
      formation in hop (Humulus lupulus var. Nugget) showed that LOXs are
      developmentally regulated throughout the process, suggesting their involvement in
      the response of internodes to wounding, nodule formation, and plantlet
      regeneration from these nodules. LOX activity and lipid peroxides exhibited a
      huge increase during the first week of culture, which may indicate a role for LOX
      and LOX products in response to wounding in hop, as reported for other systems.
      Western blotting analysis showed a de novo synthesis of LOX isoenzymes in
      response to wounding and the detection of three different isoenzymes. Confocal
      analysis of LOX immunofluorescence revealed the presence of the enzyme in
      cortical cells of induced internodes and in prenodular cells, mostly appearing as
      cytoplasmic spots. Some of them were identified as lipid bodies by cytochemical
      and double immunofluorescence assays, suggesting the involvement of a lipid body
      LOX during nodule formation. Immunogold labeling detected LOX in peroxisomes,
      lipid bodies, and plastids of nodular cells. Quantification of the labeling
      density provided statistical significance for the localization of LOX (three
      different isoenzymes) in the three compartments, which suggested a possible
      involvement of LOX in metabolic functions of these organelles during organogenic
      nodule formation and plantlet regeneration.

PMID- 14729876
TI  - Expression of MAL2, an integral protein component of the machinery for
      basolateral-to-apical transcytosis, in human epithelia.
AB  - MAL2, an integral membrane protein of the MAL family, is an essential component
      of the machinery necessary for the indirect transcytotic route of apical
      transport in human hepatoma HepG2 cells. To characterize the range of human
      epithelia that use MAL2-mediated pathways of transport, we carried out an
      immunohistochemical survey of normal tissues using a monoclonal antibody specific
      to the MAL2 protein. MAL2 expression was detected in specific types of normal
      epithelial cells throughout the respiratory system, the gastrointestinal and
      genitourinary tracts, in exocrine and endocrine glands, and in hepatocytes. Many
      different types of specialized secretory cells, either organized in discrete
      clusters (e.g., endocrine cells in the pancreas) or in endocrine glands (e.g.,
      prostate), were also positive for MAL2. In addition to epithelial cells,
      peripheral neurons, mast cells, and dendritic cells were found to express MAL2.
      For comparison with normal epithelial tissue, different types of renal carcinoma
      were also analyzed, revealing alterations in MAL2 expression/distribution
      dependent on the particular histological type of the tumor. Our results allow the
      prediction of the existence of MAL2-based trafficking pathways in specific cell
      types and suggest applications of the anti-MAL2 antibody for the characterization
      of neoplastic tissue.

PMID- 14729877
TI  - Generation and characterization of anti-MUC4 monoclonal antibodies reactive with
      normal and cancer cells in humans.
AB  - We have previously cloned the full-length cDNA (approximately 28 Kb) and
      established the complete genomic organization (25 exons/introns over 100 kb) of
      the human MUC4 mucin. This large molecule is predicted to protrude over 2 microm
      above the cell surface, in which MUC4alpha is an extracellular mucin-type
      glycoprotein subunit and MUC4beta is the transmembrane subunit. Over two thirds
      of the encoded protein sequence consists of 16-amino-acid tandem repeats (TR),
      which are flanked by unique sequences. In this study we generated and
      characterized monoclonal antibodies (MAbs) directed against the TR region of
      MUC4. Mice were immunized with a KLH-conjugated MUC4 TR peptide,
      STGDTTPLPVTDTSSV. Several clones were purified by three rounds of limited
      dilutions and stable clones presenting a sustained antibody production were
      selected for subsequent characterization. Antibodies were tested for their
      reactivity and specificity to recognize the MUC4 peptide and further screened by
      enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. One of
      the MAbs (8G7) was strongly reactive against the MUC4 peptide and with native
      MUC4 from human tissues or pancreatic cancer cells in Western blotting,
      immunohistochemistry, and confocal analysis. Anti-MUC4 MAb may represent a
      powerful tool for the study of MUC4 function under normal and pathological
      conditions and for diagnosis of solid tumors including those in the breast,
      pancreas, lungs, and ovaries.

PMID- 14729878
TI  - Regulation of leptin mRNA and protein expression in pituitary somatotropes.
AB  - Leptin, the ob protein, regulates food intake and satiety and can be found in the
      anterior pituitary. Leptin antigens and mRNA were studied in the anterior
      pituitary (AP) cells of male and female rats to learn more about its regulation.
      Leptin antigens were found in over 40% of cells in diestrous or proestrous female
      rats and in male rats. Lower percentages of AP cells were seen in the estrous
      population (21 +/- 7%). During peak expression of antigens, co-expression of
      leptin and growth hormone (GH) was found in 27 +/- 4% of AP cells. Affinity
      cytochemistry studies detected 24 +/- 3% of AP cells with leptin proteins and
      growth hormone releasing hormone (GHRH) receptors. These data suggested that
      somatotropes were a significant source of leptin. To test regulatory factors,
      estrous and diestrous AP populations were treated with estrogen (100 pM) and/or
      GHRH (2 nM) to learn if either would increase leptin expression in GH cells. To
      rule out the possibility that the immunoreactive leptin was bound to receptors in
      somatotropes, leptin mRNA was also detected by non-radioactive in situ
      hybridization in this group of cells. In estrous female rats, 39 +/- 0.9% of AP
      cells expressed leptin mRNA, indicating that the potential for leptin production
      was greater than predicted from the immunolabeling. Estrogen and GHRH together
      (but not alone) increased percentages of cells with leptin protein (41 +/- 9%) or
      mRNA (57 +/- 5%). Estrogen and GHRH also increased the percentages of AP cells
      that co-express leptin mRNA and GH antigens from 20 +/- 2% of AP cells to 37 +/-
      5%. Although the significance of leptin in GH cells is not understood, it is
      clearly increased after stimulation with GHRH and estrogen. Because GH cells also
      have leptin receptors, this AP leptin may be an autocrine or paracrine regulator
      of pituitary cell function.

PMID- 14729881
TI  - Once a week is not enough: effects of a widely implemented group based exercise
      programme for older adults; a randomised controlled trial.
AB  - OBJECTIVES: To determine the effects of gymnastics on the health related quality
      of life (HRQoL) and functional status of independently living people, aged 65 to
      80 years. Gymnastics formed part of the More Exercise for Seniors (MBvO in Dutch)
      programme, a group based exercise programme for older adults in the Netherlands.
      It has been widely implemented since 1980. DESIGN: Randomised controlled trial
      with pretest and post-test measurements. INTERVENTION: The exercise programme
      given by experienced instructors lasted 10 weeks and was given weekly (MBvO1; n =
      125, six groups) or twice weekly (MBvO2; n = 68, six groups). The control group
      (n = 193) was offered a health education programme. SETTING: Community dwelling
      of older people, with a comparatively low level of fitness as assessed with the
      Groningen Fitness test for the Elderly. RESULTS: No significant effects were
      found on the HRQoL (Vitality Plus Scale, TAAQoL, and RAND-36) and the functional
      status (Physical Performance Test and the Groningen Activity Restriction Scale).
      The MBvO2 group, with a low level of physical activity at baseline, showed the
      only improvement found on the Vitality Plus Scale (F = 4.53; p = 0.01).
      CONCLUSIONS: MBvO gymnastics once a week did not provide benefits in HRQoL and
      functional status after 10 weeks. However, participants with a low level of
      physical activity may benefit from MBvO gymnastics if they participate twice a
      week. To improve the health of the general public, sedentary older adults should
      be recruited and encouraged to combine MBvO with the health enhancing physical
      activity guidelines.

PMID- 14729882
TI  - Are GP practice prescribing rates for coronary heart disease drugs equitable? A
      cross sectional analysis in four primary care trusts in England.
AB  - STUDY OBJECTIVE: To analyse the associations between proxies of healthcare need
      and GP practice prescribing rates for five major coronary heart disease (CHD)
      drug groups. DESIGN: Cross sectional secondary analysis. SETTING: Four primary
      care trusts (PCTs 1-4) in the north west of England, encompassing 132 GP
      practices. RESULTS: Prescribing rates were generally positively associated with
      the percentage of patients aged 55-74 years and PASS-PUs (regionally specific
      prevalence, age, and sex standardised prescribing units). However, the percentage
      of patients aged over 75 years showed a lack of association with prescribing
      rates in all PCTs other than PCT2. Correlations with the proportion of South
      Asian patients were generally negative, particularly in PCT2, PCT4, and the
      combined dataset. There was a general lack of association with deprivation
      proxies and SMRs for CHD, although there were negative associations with both
      variables in PCT4 and the combined dataset. Scatter plots showed that GP
      practices with similar prescribing rates had widely differing levels of
      comparative healthcare need, and GP practices with similar levels of healthcare
      need had widely differing prescribing rates. CONCLUSION: GP prescribing rates in
      some PCTs were negatively associated with proxies of healthcare need based on
      patient age (patients aged over 75 years), ethnicity, levels of deprivation, and
      SMRs for CHD. As such, this study suggests that prescribing rates in these PCTs
      may be inequitable as they are not positively associated with healthcare need.
      This study may form the baseline for further studies to assess the effectiveness
      of the NSF for CHD in reducing the inequities in prescribing rates.

PMID- 14729883
TI  - Influential women in occupational health. Vilma R Hunt--nuclear expert, science
      educator.

PMID- 14729884
TI  - Impact of regionalisation of cardiac surgery in Emilia-Romagna, Italy.
AB  - STUDY OBJECTIVE: Assessment of the impact of the regionalisation of cardiac
      surgery through the organisational form of a hub&spoke model introduced in the
      year 2000. DESIGN: Case mix adjusted before (1998-1999)-after (2000-2002)
      comparison of: (a) in-hospital and 30 days mortality rates; (b) proportion of
      patients timely (within one day) referred for surgery from spoke to hub centres;
      (c) patients' waiting times to surgery. SETTING: Emilia-Romagna, an Italian
      region with four million residents. PATIENTS: 16,512 patients aged > or =18 years
      and referred to cardiac surgery over the period 1998-2002. MAIN RESULTS: Overall,
      taking into account differences in case mix across the whole study period, the
      implementation of the regionalisation policy was associated with a 22% reduction
      (OR: 0.79, 95%CI: 0.66 to 0.93) in in-hospital mortality rate. The corresponding
      figure for 30 day mortality was 18% (OR: 0.82: 95%CI: 0.69 to 0.98). The
      individual centres' volume of cases changed over the study period for all
      hospitals but two, and the biggest reduction in mortality was seen at the centre
      with the largest increase in caseload. CONCLUSIONS: This study provides
      additional evidence on the benefit of regionalisation of cardiac surgery
      interventions. The system allowed each centre to reach the minimum caseload
      required to assure good quality of care. These findings suggest that policies
      aimed at increasing cooperation rather than competition among health service
      providers have a positive impact on quality of care. Timely referrals for surgery
      increased by 21% (95%CI: 1.12 to 1.31), and mean waiting times were reduced by
      7.5 average days (95%CI: -10.33 to -4.71).

PMID- 14729887
TI  - Developmental origins of adult health and disease.

PMID- 14729886
TI  - Predicted health impacts of urban air quality management.
AB  - STUDY OBJECTIVE: The 1995 UK Environment Act required local authorities to review
      air quality and, where UK National Air Quality Strategy objectives (except ozone)
      are likely to be exceeded in 2005, to declare local air quality management areas
      and prepare action plans. This study modelled the impacts on health of reductions
      from current levels of PM(10) to these objectives. DESIGN: The framework for
      conducting quantified health impact assessment assessed causality, then, if
      appropriate, examined the shape and magnitude of the exposure-response relations.
      The study modelled declines in pollution to achieve the objectives, then modelled
      the numbers of deaths and admissions affected if air pollution declined from
      existing levels to meet the objectives, using routine data. SETTING: Westminster,
      central London. MAIN RESULTS: Attaining the 2004 PM(10) 24 hour objective in
      Westminster results in 1-21 lives no longer shortened in one year (annual deaths
      1363). Reducing exceedences from 35 to seven almost doubles the estimates. The
      2009 objective for the annual mean requires a substantial reduction in PM(10),
      which would delay 8-20 deaths. About 20 respiratory and 14-20 circulatory
      admissions would be affected and around 5% of emergency hospital attendances for
      asthma by attaining the lower annual mean target. The effects of long term
      exposure to particulates may be an order of magnitude higher: models predict
      about 24 deaths are delayed by reaching the 2004 annual target (40
      microg/m(3)([gravimetric])) and a hundred deaths by reducing annual mean PM(10)
      to 20 microg/m(3)([gravimetric]). CONCLUSIONS: Modelling can be used to estimate
      the potential health impacts of air quality management programmes.

PMID- 14729888
TI  - Cardiovascular epidemiology and prevention.

PMID- 14729891
TI  - Birth characteristics of offspring and parental diabetes: evidence for the fetal
      insulin hypothesis.

PMID- 14729890
TI  - Birth weight is inversely associated with coronary heart disease in post
      menopausal women: findings from the British women's heart and health study.
AB  - OBJECTIVES: (1) To assess the association between birth weight and coronary heart
      disease (CHD) risk in a cohort of post-menopausal women, (2) to determine the
      combined effects of birth weight and adult body mass index on CHD, (3) to assess
      the role of insulin resistance as a mediating factor in the associations. DESIGN:
      Cross sectional survey. SETTING: 23 British towns. PARTICIPANTS: 1394 women aged
      60-79 years. MAIN OUTCOME MEASURES: coronary heart disease (n = 199 cases).
      RESULTS: Birth weight was inversely associated with CHD: age and survivor status
      of participant's mother adjusted odds ratio (95% confidence intervals) per 1
      standard deviation (0.80 kg) increase in birth weight was 0.84 (0.72 to 0.97).
      This association strengthened to 0.80 (0.68 to 0.93) with further adjustment for
      adult body mass index, but there was no evidence of an interaction between birth
      weight and adult body mass index (p = 0.61). The association was not confounded
      by childhood or adulthood socioeconomic position or by adult smoking status of
      the participant. Adjustment for components of the insulin resistance syndrome
      attenuated the association to 0.87 (0.72 to 1.03). CONCLUSIONS: Intrauterine
      exposures that affect fetal growth also affect future adult CHD risk. The inverse
      association between birth weight and CHD may in part be mediated via insulin
      resistance.

PMID- 14729893
TI  - Seasonal congestive heart failure mortality and hospitalisation trends, Quebec
      1990-1998.
AB  - STUDY OBJECTIVE: To describe seasonal congestive heart failure (CHF) mortality
      and hospitalisations in Quebec, Canada between 1990-1998 and compare trends in
      CHF mortality and morbidity with those in France. DESIGN: Population cohort
      study. SETTING: Province of Quebec, Canada. PATIENTS: Mortality data were
      obtained from the Quebec Death Certificate Registry and hospitalisation from the
      Quebec Med-Echo hospital discharge database. Cases with primary ICD-9 code 428
      were considered cases of CHF. RESULTS: Monthly CHF mortality was higher in
      January, declined until September and then rose steadily (p<0.05). Hospital
      admissions for CHF declined from May until September (moving averages analysis
      p<0.0001). Seasonal mortality patterns observed in Quebec were similar to those
      observed in France. CONCLUSION: CHF mortality in Quebec is highest during the
      winter and declines in the summer, similar to observations in France and
      Scotland. This suggests that absolute temperatures may not necessarily be that
      important but increased CHF mortality is observed once environmental temperatures
      fall below a certain "threshold" temperature. Alternatively better internal
      heating and warmer clothing required for survival in Quebec may ameliorate
      mortality patterns despite colder external environments.

PMID- 14729894
TI  - Low job control and myocardial infarction risk in the occupational categories of
      Kaunas men, Lithuania.
AB  - STUDY OBJECTIVE: To determine the association between adverse psychosocial
      characteristics at work and risk of first myocardial infarction in the
      occupational categories of Kaunas men, Lithuania. DESIGN: The analysis was based
      upon a case-control study among full time working men in the general population
      of Kaunas. OUTCOME MEASURE: First non-fatal myocardial infarction diagnosed in
      2001-2002. The Swedish version of the demand-control questionnaire was used to
      examine the effect of job control and demands. SETTING: Kaunas, the second
      largest city in Lithuania, a former socialist country in a transition market
      economy. PARTICIPANTS: Cases were 203 men 25-64 years of age with a first non
      fatal myocardial infarction and controls were 287 men group randomly selected
      from the study base. MAIN RESULTS: Low job control had a significant effect on
      myocardial infarction risk in the general 25-64 year old Kaunas male population
      (OR = 2.68; 95% CI 1.68 to 4.28) after adjustment for age and socioeconomic
      status. Low job control was a risk factor in the occupational categories of the
      increased myocardial infarction risk (1st occupational category--legislators,
      senior officials and managers and the 8th--plant and machine operators and
      assemblers; OR = 2.78; 95% CI 1.31 to 5.93 and 2.72; 95% CI 1.56 to 4.89,
      respectively, after adjustment for age and socioeconomic status). Though the
      adjusted odds ratio estimates were significantly high for the rest of the
      occupational categories (2nd--professionals, 3rd--technicians and associate
      professionals, and 7th--craft and related trades workers). CONCLUSIONS: The
      association between low job control and first myocardial infarction risk was
      significant for all occupational categories of Kaunas men.

PMID- 14729895
TI  - Geochemistry of ground water and the incidence of acute myocardial infarction in
      Finland.
AB  - STUDY OBJECTIVE: To examine the association of spatial variation in acute
      myocardial infarction (AMI) incidence and its putative environmental determinants
      in ground water such as total water hardness, the concentration of calcium,
      magnesium, fluoride, iron, copper, zinc, nitrate, and aluminium. DESIGN: Small
      area study using Bayesian modelling and the geo-referenced data aggregated into
      10 km x 10 km cells. SETTING: The population data were obtained from Statistics
      Finland, AMI case data from the National Death Register and the Hospital
      Discharge Register, and the geochemical data from hydrogeochemical database of
      Geological Survey of Finland. PARTICIPANTS: A total of 18 946 men aged 35-74
      years with the first AMI attack in the years 1983, 1988, and 1993. MAIN RESULTS:
      One unit (in German degree degrees dH) increment in water hardness decreased the
      risk of AMI by 1%. Geochemical elements in ground water included in this study
      did not show a statistically significant effect on the incidence and spatial
      variation of AMI, even though suggestive findings were detected for fluoride
      (protective), iron and copper (increasing). CONCLUSIONS: The results of this
      study with more specific Bayesian statistical analysis confirm findings from
      earlier observations of the inverse relation between water hardness and coronary
      heart disease. The role of environmental geochemistry in the geographical
      variation of the AMI incidence should be studied further in more detail
      incorporating the individual intake of both food borne and water borne nutrients.
      Geochemical-spatial analysis provides a basis for the selection of areas suitable
      for such research.

PMID- 14729896
TI  - Case-control study of the association between kava use and ischaemic heart
      disease in Aboriginal communities in eastern Arnhem Land (Northern Territory)
      Australia.

PMID- 14729897
TI  - Skin cancer in people with multiple sclerosis: a record linkage study.
AB  - OBJECTIVE: The prevalence of multiple sclerosis (MS) varies with latitude: it
      increases with distance from the equator in both hemispheres. To seek evidence on
      whether solar radiation is a protective factor for MS, this study investigated
      whether skin cancer, as an indicator of solar radiation, is less common in people
      with MS than in others. DESIGN: Analysis of a database of linked hospital records
      and death certificates. SETTING: The Oxford Region of the National Health
      Service, England. SUBJECTS: A cohort comprising all people in the database with
      MS, and comparison cohorts of people with other diseases. RESULTS: Skin cancer
      was significantly less common in people with MS than in the main comparison
      cohort (rate ratio 0.49; 95% confidence interval 0.24 to 0.91). There was no
      general deficit of cancer in the MS cohort, and no deficit of skin cancer in
      cohorts of people with other autoimmune or neurological diseases. CONCLUSION: The
      findings support the hypothesis that solar radiation may have a protective
      influence on the development of MS.

PMID- 14729898
TI  - Country of birth, socioeconomic position, and healthcare expenditure: a
      multilevel analysis of Malmo, Sweden.
AB  - STUDY OBJECTIVE: The principle of equity aims to guarantee allocation of
      healthcare resources on the basis of need. Therefore, people with a low income
      and persons living alone are expected to have higher healthcare expenditures.
      Besides these individual characteristics healthcare expenditure may be influenced
      by country of birth. This study therefore aimed to investigate the role of
      country of birth in explaining individual healthcare expenditure. DESIGN:
      Multilevel regression model based on individuals (first level) and their country
      of birth (second level). SETTING: The city of Malmo, Sweden. PARTICIPANTS: All
      the 52 419 men aged 40-80 years from 130 different countries of birth, who were
      living in Malmo, Sweden, during 1999. MAIN RESULTS: At the individual level,
      persons with a low income and persons living alone showed a higher healthcare
      expenditure, with regression coefficients (and 95% confidence intervals) being
      0.358 (0.325 to 0.392) and 0.197 (0.165 to 0.230), respectively. Country of birth
      explained a considerable part (18% and 13%) of the individual differences in the
      probability of having a low income and living alone, respectively. However, this
      figure was only 3% for having some health expenditure, and barely 0.7% with
      regard to costs in the 74% of the population with some health expenditure.
      CONCLUSIONS: Malmo is a socioeconomically segregated city, in which the country
      of birth seems to play only a minor part in explaining individual differences in
      total healthcare expenditure. These differences seem instead to be determined by
      individual low income and living alone.

PMID- 14729899
TI  - Predicting geographical variations in behavioural risk factors: an analysis of
      physical and mental healthy days.
AB  - STUDY OBJECTIVES: To determine the validity of physical and mental unhealthy days
      as summary measures for county health status and to forward a method for
      examining county level health trends using a single year of data from the
      Behavioral Risk Factor Surveillance System (BRFSS). DESIGN: The study analysed
      geographical variation in physical and mental unhealthy days at the state and
      county level using the 2000 BRFSS. Whereas state level analyses used individual
      level data, this research conducted multilevel regression analysis using county
      level data as independent variables and individual level reports of physical and
      mental unhealthy days as dependent variables. SETTING: Population based samples
      of non-institutionalised civilian adult residents from each of the 50 states and
      the District of Columbia in the United States. MAIN RESULTS: Socioeconomic
      variables predicted similar mean numbers of physical and mental unhealthy days at
      both the state and county level, validating the county level analyses. County
      level disability rates were strongly associated with county mean unhealthy days.
      Using the regression method we forward, it is possible to analyse county level
      trends using a single year of BRFSS data. CONCLUSIONS: Physical and mental
      unhealthy days may be used as valid summary measures of county health status.
      Regression models may be used to assist local decision makers in assessing the
      needs of their communities and may be used to improve health resource allocation
      within states.

PMID- 14729900
TI  - Smoking verification and the risk of myocardial infarction.

PMID- 14729901
TI  - Air pollution and asthma in children.

PMID- 14729902
TI  - Fibrinogen, social position, and risk of heart disease.

PMID- 14729903
TI  - Smoking cessation services may not reduce inequalities.

PMID- 14729905
TI  - T-complex polypeptide-1 interacts with the erythrocyte cytoskeleton in response
      to elevated temperatures.
AB  - Chaperonins are double ring complexes composed of highly conserved 60-kDa protein
      subunits that are divided into two subgroups. Group II chaperonins are found in
      archaea and the cytoplasm of eukarya and are believed to function like other
      chaperonins as part of a protein folding system. We report here that human
      erythrocytes contain the group II chaperonin T-complex polypeptide 1 (TCP-1) and
      that this complex translocates from the cytoplasm to the cytoskeleton in response
      to heat treatment in the absence of overt cell damage. Identification as TCP-1
      was determined by immunodetection for TCP-1alpha and corroborated by mass
      spectroscopy peptide sequencing. Direct visualization by immunofluorescence
      confirmed peripherally localized TCP-1 in response to heat treatment.
      Temperatures ranging from 37-50 degrees C were demonstrated to have distinct
      kinetic profiles of induced translocation. Heat-induced binding was shown by
      Triton shell analysis to be specifically associated with the cytoskeletal
      proteins. Furthermore, the binding was reversible following removal of the
      stimulatory condition. A stabilizing process is hypothesized based on the known
      interactions of chaperonins.

PMID- 14729906
TI  - A novel interaction of Cap-binding protein complexes eukaryotic initiation factor
      (eIF) 4F and eIF(iso)4F with a region in the 3'-untranslated region of satellite
      tobacco necrosis virus.
AB  - Satellite tobacco necrosis virus (STNV) RNA is naturally uncapped at its 5' end
      and lacks polyadenylation at its 3' end. Despite lacking these two hallmarks of
      eukaryotic mRNAs, STNV-1 RNA is translated very efficiently. A approximately 130
      nucleotide translational enhancer (TED), located 3' to the termination codon, is
      necessary for efficient cap-independent translation of STNV-1 RNA. The STNV-1 TED
      RNA fragment binds to the eukaryotic cap-binding complexes, initiation factor
      (eIF) 4F and eIF(iso)4F, as measured by nitrocellulose binding and fluorescence
      titration. STNV-1 TED is a potent inhibitor of in vitro translation when added in
      trans. This inhibition is reversed by the addition of eIF4F or eIF(iso)4F, and
      the subunits of eIF4F and eIF(iso)4F cross-link to STNV-1 TED, providing
      additional evidence that these factors interact directly with STNV-1 TED.
      Deletion mutagenesis of the STNV-1 TED indicates that a minimal region of
      approximately 100 nucleotides is necessary to promote cap-independent translation
      primarily through interaction with the cap binding subunits (eIF4E or eIF(iso)4E)
      of eIF4F or eIF(iso)4F.

PMID- 14729907
TI  - The spatial and temporal dynamics of pleckstrin homology domain binding at the
      plasma membrane measured by imaging single molecules in live mouse myoblasts.
AB  - Pleckstrin homology (PH) domains act to target proteins to the plasma membrane
      and intracellular vesicles by binding to specific phosphoinositol phospholipids.
      We have investigated the binding kinetics of PH domains found in the tail region
      of the molecular motor, myosin X. Using total internal reflection fluorescence
      microscopy, we observed binding and release of individual PH domains fused to
      green fluorescent protein at the plasma membrane of living cells. Individual
      spots of light corresponding to single fluorescently tagged molecules were imaged
      onto a sensitive camera system, and digital image processing was then used to
      identify each fluorophore and store its trajectory in time and space. The PH
      domains bound with an apparent on-rate of 0.03 microm(-1) microm(-2) s(-1) and a
      detachment rate constant of 0.05 s(-1). The average residency time of the domains
      at the plasma membrane was about 20s. We found very limited movement of the
      membrane-bound PH domains in the mouse myoblast cells that we studied. This
      implies that the PH domains must either be attached to the cytoskeleton or
      corralled in a lipid compartment. Localization of the PH domains together with
      their rapid detachment rate is probably important in controlling the response of
      myosin X to signaling events and in regulating its cellular function.

PMID- 14729908
TI  - InsP3R-associated cGMP kinase substrate (IRAG) is essential for nitric oxide
      induced inhibition of calcium signaling in human colonic smooth muscle.
AB  - Nitric oxide (NO)-mediated relaxation of colonic smooth muscle is crucial for the
      maintenance of human gut function. The molecular mechanisms of NO-dependent
      smooth muscle relaxation involve cyclic GMP-mediated inhibition of store
      dependent calcium signaling. Recently, IRAG (inositol 1,4,5-trisphophate receptor
      associated cGMP kinase substrate) has been characterized as a novel target
      molecule of cGMP-dependent protein kinase (cGKI) mediating NO-/cGMP-dependent
      inhibition of inositol 1,4,5-trisphosphate (InsP(3))-dependent calcium release in
      transfected COS cells. The aim of the present study was to characterize IRAG
      expression and its functional role in NO-dependent signaling in human colonic
      smooth muscle. Reverse transcriptase-PCR revealed IRAG mRNA expression in human
      colon, rectum, and cultured colonic smooth muscle cells. In cultured human
      colonic smooth muscle cells, bradykinin (BK) elicited InsP(3)-dependent calcium
      transients that were repeatable and independent of extracellular calcium. The NO
      donor sodium nitroprusside and the specific cGK activator 8-(4
      chlorophenylthio)guanosine-3',5'-cyclic-monophosphate (8-pCPT-cGMP) significantly
      inhibited BK-induced increase in intracellular calcium. Cells transfected with
      antisense oligonucleotides raised against IRAG (IRAG-AS) showed strongly
      decreased IRAG protein expression. In these cells, sodium nitroprusside and 8
      pCPT-cGMP both failed to modulate BK-induced calcium transients. Thus, endogenous
      IRAG appears to be essentially involved in the NO/cGK-dependent inhibition of
      InsP(3)-dependent Ca(2+)-signaling in colonic smooth muscle.

PMID- 14729909
TI  - Bacteriophage T4 32 protein is required for helicase-dependent leading strand
      synthesis when the helicase is loaded by the T4 59 helicase-loading protein.
AB  - In the bacteriophage T4 DNA replication system, T4 gene 59 protein binds
      preferentially to fork DNA and accelerates the loading of the T4 41 helicase. 59
      protein also binds the T4 32 single-stranded DNA-binding protein that coats the
      lagging strand template. Here we explore the function of the strong affinity
      between the 32 and 59 proteins at the replication fork. We show that, in contrast
      to the 59 helicase loader, 32 protein does not bind forked DNA more tightly than
      linear DNA. 32 protein displays a strong binding polarity on fork DNA, binding
      with much higher affinity to the 5' single-stranded lagging strand template arm
      of a model fork, than to the 3' single-stranded leading strand arm. 59 protein
      promotes the binding of 32 protein on forks too short for cooperative binding by
      32 protein. We show that 32 protein is required for helicase-dependent leading
      strand DNA synthesis when the helicase is loaded by 59 protein. However, 32
      protein is not required for leading strand synthesis when helicase is loaded,
      less efficiently, without 59 protein. Leading strand synthesis by wild type T4
      polymerase is strongly inhibited when 59 protein is present without 32 protein.
      Because 59 protein can load the helicase on forks without 32 protein, our results
      are best explained by a model in which 59 helicase loader at the fork prevents
      the coupling of the leading strand polymerase and the helicase, unless the
      position of 59 protein is shifted by its association with 32 protein.

PMID- 14729910
TI  - The Arabidopsis thaliana dihydroxyacetone phosphate reductase gene SUPPRESSSOR OF
      FATTY ACID DESATURASE DEFICIENCY1 is required for glycerolipid metabolism and for
      the activation of systemic acquired resistance.
AB  - Systemic acquired resistance (SAR) is a broad-spectrum resistance mechanism in
      plants that is activated in naive organs after exposure of another organ to a
      necrotizing pathogen. The organs manifesting SAR exhibit an increase in levels of
      salicylic acid (SA) and expression of the PATHOGENESIS-RELATED1 (PR1) gene. SA
      signaling is required for the manifestation of SAR. We demonstrate here that the
      Arabidopsis thaliana suppressor of fatty acid desaturase deficiency1 (sfd1)
      mutation compromises the SAR-conferred enhanced resistance to Pseudomonas
      syringae pv maculicola. In addition, the sfd1 mutation diminished the SAR
      associated accumulation of elevated levels of SA and PR1 gene transcript in the
      distal leaves of plants previously exposed to an avirulent pathogen. However, the
      basal resistance to virulent and avirulent strains of P. syringae and the
      accumulation of elevated levels of SA and PR1 gene transcript in the pathogen
      inoculated leaves of sfd1 were not compromised. Furthermore, the application of
      the SA functional analog benzothiadiazole enhanced disease resistance in the sfd1
      mutant plants. SFD1 encodes a putative dihydroxyacetone phosphate (DHAP)
      reductase, which complemented the glycerol-3-phosphate auxotrophy of the DHAP
      reductase-deficient Escherichia coli gpsA mutant. Plastid glycerolipid
      composition was altered in the sfd1 mutant plant, suggesting that SFD1 is
      involved in lipid metabolism and that an SFD1 product lipid(s) is important for
      the activation of SAR.

PMID- 14729911
TI  - The Arabidopsis thaliana REDUCED EPIDERMAL FLUORESCENCE1 gene encodes an aldehyde
      dehydrogenase involved in ferulic acid and sinapic acid biosynthesis.
AB  - Recent research has significantly advanced our understanding of the
      phenylpropanoid pathway but has left in doubt the pathway by which sinapic acid
      is synthesized in plants. The reduced epidermal fluorescence1 (ref1) mutant of
      Arabidopsis thaliana accumulates only 10 to 30% of the sinapate esters found in
      wild-type plants. Positional cloning of the REF1 gene revealed that it encodes an
      aldehyde dehydrogenase, a member of a large class of NADP(+)-dependent enzymes
      that catalyze the oxidation of aldehydes to their corresponding carboxylic acids.
      Consistent with this finding, extracts of ref1 leaves exhibit low sinapaldehyde
      dehydrogenase activity. These data indicate that REF1 encodes a sinapaldehyde
      dehydrogenase required for sinapic acid and sinapate ester biosynthesis. When
      expressed in Escherichia coli, REF1 was found to exhibit both sinapaldehyde and
      coniferaldehyde dehydrogenase activity, and further phenotypic analysis of ref1
      mutant plants showed that they contain less cell wall-esterified ferulic acid.
      These findings suggest that both ferulic acid and sinapic acid are derived, at
      least in part, through oxidation of coniferaldehyde and sinapaldehyde. This route
      is directly opposite to the traditional representation of phenylpropanoid
      metabolism in which hydroxycinnamic acids are instead precursors of their
      corresponding aldehydes.

PMID- 14729912
TI  - A plasma membrane protein from Zea mays binds with the herbivore elicitor
      volicitin.
AB  - Volicitin (17-hydroxylinolenoyl-l-Gln) present in the regurgitant of Spodoptera
      exigua (beet armyworm caterpillars) activates the emission of volatile organic
      compounds (VOCs) when in contact with damaged Zea mays cv Delprim (maize) leaves.
      VOC emissions in turn serve as a signaling defense for the plant by attracting
      female parasitic wasps that prey on herbivore larvae. A tritiated form of
      volicitin was synthesized and shown to induce volatiles in the same fashion as
      the biological form. [(3)H]-l-volicitin rapidly, reversibly, and saturably bound
      to enriched plasma membrane fractions isolated from Z. mays leaves with an
      apparent K(d) of 1.3 nM and a Hill coefficient of 1.07. Analog studies showed
      that the l-Gln and hydroxy moieties of volicitin play an important role in
      binding. Treatment of plants with methyl jasmonate (MeJA) increased the total
      binding of [(3)H]-l-volicitin to the enriched plasma membrane more than
      threefold, suggesting that MeJA activates transcription of the gene encoding the
      binding protein. S. exigua feeding also increased total binding fourfold.
      Cycloheximide pretreatment of plants significantly decreased binding of
      radiolabeled volicitin to the enriched plasma membrane. These data provide the
      first experimental evidence that initiation of plant defenses in response to
      herbivore damage can be mediated by a binding protein-ligand interaction.

PMID- 14729913
TI  - Extensive maternal DNA hypomethylation in the endosperm of Zea mays.
AB  - A PCR-based genomic scan has been undertaken to estimate the extent and ratio of
      maternally versus paternally methylated DNA regions in endosperm, embryo, and
      leaf of Zea mays (maize). Analysis of several inbred lines and their reciprocal
      crosses identified a large number of conserved, differentially methylated DNA
      regions (DMRs) that were specific to the endosperm. DMRs were hypomethylated at
      specific methylation-sensitive restriction sites upon maternal transmission,
      whereas upon paternal transmission, the methylation levels were similar to those
      observed in embryo and leaf. Maternal hypomethylation was extensive and offers a
      likely explanation for the 13% reduction in methyl-cytosine content of the
      endosperm compared with leaf tissue. DMRs showed identity to expressed genic
      regions, were observed early after fertilization, and maintained at a later stage
      of endosperm development. The implications of extensive maternal hypomethylation
      with respect to endosperm development and epigenetic reprogramming will be
      discussed.

PMID- 14729914
TI  - In-depth analysis of the thylakoid membrane proteome of Arabidopsis thaliana
      chloroplasts: new proteins, new functions, and a plastid proteome database.
AB  - An extensive analysis of the Arabidopsis thaliana peripheral and integral
      thylakoid membrane proteome was performed by sequential extractions with salt,
      detergent, and organic solvents, followed by multidimensional protein separation
      steps (reverse-phase HPLC and one- and two-dimensional electrophoresis gels),
      different enzymatic and nonenzymatic protein cleavage techniques, mass
      spectrometry, and bioinformatics. Altogether, 154 proteins were identified, of
      which 76 (49%) were alpha-helical integral membrane proteins. Twenty-seven new
      proteins without known function but with predicted chloroplast transit peptides
      were identified, of which 17 (63%) are integral membrane proteins. These new
      proteins, likely important in thylakoid biogenesis, include two rubredoxins, a
      potential metallochaperone, and a new DnaJ-like protein. The data were integrated
      with our analysis of the lumenal-enriched proteome. We identified 83 out of 100
      known proteins of the thylakoid localized photosynthetic apparatus, including
      several new paralogues and some 20 proteins involved in protein insertion,
      assembly, folding, or proteolysis. An additional 16 proteins are involved in
      translation, demonstrating that the thylakoid membrane surface is an important
      site for protein synthesis. The high coverage of the photosynthetic apparatus and
      the identification of known hydrophobic proteins with low expression levels, such
      as cpSecE, Ohp1, and Ohp2, indicate an excellent dynamic resolution of the
      analysis. The sequential extraction process proved very helpful to validate
      transmembrane prediction. Our data also were cross-correlated to chloroplast
      subproteome analyses by other laboratories. All data are deposited in a new
      curated plastid proteome database (PPDB) with multiple search functions
      (http://cbsusrv01.tc.cornell.edu/users/ppdb/). This PPDB will serve as an
      expandable resource for the plant community.

PMID- 14729915
TI  - The YABBY gene DROOPING LEAF regulates carpel specification and midrib
      development in Oryza sativa.
AB  - In this article, we report that carpel specification in the Oryza sativa (rice)
      flower is regulated by the floral homeotic gene DROOPING LEAF (DL) that is
      distinct from the well-known ABC genes. Severe loss-of-function mutations of DL
      cause complete homeotic transformation of carpels into stamens. Molecular cloning
      reveals that DL is a member of the YABBY gene family and is closely related to
      the CRABS CLAW (CRC) gene of Arabidopsis thaliana. DL is expressed in the
      presumptive region (carpel anlagen), where carpel primordia would initiate, and
      in carpel primordia. These results suggest that carpel specification is regulated
      by DL in rice flower development. Whereas CRC plays only a partial role in carpel
      identity, DL may have been recruited to have the more essential function of
      specifying carpels during the evolution of rice. We also show that DL interacts
      antagonistically with class B genes and controls floral meristem determinacy. In
      addition, severe and weak dl alleles fail to form a midrib in the leaf. The
      phenotypic analysis of dl mutants, together with analyses of the spatial
      expression patterns and ectopic expression of DL, demonstrate that DL regulates
      midrib formation by promoting cell proliferation in the central region of the
      rice leaf.

PMID- 14729916
TI  - Activation of gibberellin biosynthesis and response pathways by low temperature
      during imbibition of Arabidopsis thaliana seeds.
AB  - Exposure of imbibed seeds to low temperature (typically 4 degrees C) is widely
      used to break seed dormancy and to improve the frequency of germination. However,
      the mechanism by which temperature accelerates germination is largely unknown.
      Using DNA microarray and gas chromatography-mass spectrometry analyses, we found
      that a subset of gibberellin (GA) biosynthesis genes were upregulated in response
      to low temperature, resulting in an increase in the level of bioactive GAs and
      transcript abundance of GA-inducible genes in imbibed Arabidopsis thaliana seeds.
      Using a loss-of-function mutant, the cold-inducible GA biosynthesis gene,
      AtGA3ox1, was shown to play an essential role in mediating the effect of low
      temperature. Besides temperature, AtGA3ox1 also is positively regulated by active
      phytochrome and negatively regulated by GA activity. We show that both red light
      and GA deficiency act in addition to low temperature to elevate the level of
      AtGA3ox1 transcript, indicating that multiple signals are integrated by the
      AtGA3ox1 gene to control seed germination. When induced by low temperature,
      AtGA3ox1 mRNA was detectable by in situ RNA hybridization in an additional set of
      cell types relative to that in red light-induced seeds. Our results illustrate
      that the GA biosynthesis and response pathways are activated during seed
      imbibition at low temperature and suggest that the cellular distribution of
      bioactive GAs may be altered under different light and temperature conditions.

PMID- 14729917
TI  - MASSUGU2 encodes Aux/IAA19, an auxin-regulated protein that functions together
      with the transcriptional activator NPH4/ARF7 to regulate differential growth
      responses of hypocotyl and formation of lateral roots in Arabidopsis thaliana.
AB  - We have isolated a dominant, auxin-insensitive mutant of Arabidopsis thaliana,
      massugu2 (msg2), that displays neither hypocotyl gravitropism nor phototropism,
      fails to maintain an apical hook as an etiolated seedling, and is defective in
      lateral root formation. Yet other aspects of growth and development of msg2
      plants are almost normal. These characteristics of msg2 are similar to those of
      another auxin-insensitive mutant, non-phototropic hypocotyl4 (nph4), which is a
      loss-of-function mutant of AUXIN RESPONSE FACTOR7 (ARF7) (Harper et al., 2000).
      Map-based cloning of the MSG2 locus reveals that all four mutant alleles result
      in amino acid substitutions in the conserved domain II of an Auxin/Indole-3
      Acetic Acid protein, IAA19. Interestingly, auxin inducibility of MSG2/IAA19 gene
      expression is reduced by 65% in nph4/arf7. Moreover, MSG2/IAA19 protein binds to
      the C-terminal domain of NPH4/ARF7 in a Saccharomyces cerevisiae (yeast) two
      hybrid assay and to the whole latter protein in vitro by pull-down assay. These
      results suggest that MSG2/IAA19 and NPH4/ARF7 may constitute a negative feedback
      loop to regulate differential growth responses of hypocotyls and lateral root
      formation.

PMID- 14729918
TI  - Interchromatid and interhomolog recombination in Arabidopsis thaliana.
AB  - Intermolecular recombination events were monitored in Arabidopsis thaliana lines
      using specially designed recombination traps consisting of tandem disrupted beta
      glucuronidase or luciferase reporter genes in direct repeat orientation.
      Recombination frequencies (RFs) varied between the different lines, indicating
      possible position effects influencing intermolecular recombination processes. The
      RFs between sister chromatids and between homologous chromosomes were measured in
      plants either hemizygous or homozygous for a transgene locus. The RFs in
      homozygous plants exceeded those of hemizygous plants by a factor of >2, implying
      that in somatic plant cells both sister chromatid recombination and recombination
      between homologous chromosomes exist for recombinational DNA repair. In addition,
      different DNA-damaging agents stimulated recombination in homozygous and
      hemizygous plants to different extents in a manner dependent on the type of DNA
      damage and on the genomic region. The genetic and molecular analysis of
      recombination events showed that most of the somatic recombination events result
      from gene conversion, although a pop-out event has also been characterized.

PMID- 14729919
TI  - Divergent roles in Arabidopsis thaliana development and defense of two homologous
      genes, aberrant growth and death2 and AGD2-LIKE DEFENSE RESPONSE PROTEIN1,
      encoding novel aminotransferases.
AB  - The disease-resistant Arabidopsis thaliana aberrant growth and death2 (agd2-1)
      mutant has elevated levels of the defense signal salicylic acid (SA), altered
      leaf morphology, and mild dwarfism. AGD2 and its close homolog ALD1 (for AGD2
      LIKE DEFENSE RESPONSE PROTEIN1) encode aminotransferases that act on an
      overlapping set of amino acids in vitro. However, kinetic parameters indicate
      that AGD2 and ALD1 may drive the aminotransferase reaction in opposite
      directions. ALD1-deficient mutants have the opposite phenotypes from agd2-1,
      showing reduced SA production and increased disease susceptibility. Furthermore,
      ALD1 transcript levels are elevated in agd2-1 and are induced in the wild type by
      bacterial pathogen infection. ALD1 is responsible for some of the elevated SA
      content and a majority of the disease resistance and dwarfism of agd2-1. A
      complete knockout of AGD2 renders embryos inviable. We suggest that AGD2
      synthesizes an important amino acid-derived molecule that promotes development
      and suppresses defenses, whereas ALD1 generates a related amino acid-derived
      molecule important for activating defense signaling.

PMID- 14729920
TI  - Function of the C-terminus of phi29 DNA polymerase in DNA and terminal protein
      binding.
AB  - The thumb subdomain, located in various family B DNA polymerases in the C
      terminal region, has been shown in their crystal structures to move upon binding
      of DNA, changing its conformation to nearly completely wrap around the DNA. It
      has therefore been involved in DNA binding. In agreement with this, partial
      proteolysis studies of phi29 DNA polymerase have shown that the accessibility of
      the cleavage sites located in their C-terminal region is reduced in the presence
      of DNA or terminal protein (TP), indicating that a conformational change occurs
      in this region upon substrate binding and suggesting that this region might be
      involved in DNA and TP binding. Therefore, we have studied the role of the C
      terminus of phi29 DNA polymerase by deletion of the last 13 residues of this
      enzyme. This fragment includes a previously defined region conserved in family B
      DNA polymerases. The resulting DNA polymerase Delta13 was strongly affected in
      DNA binding, resulting in a distributive replication activity. Additionally, the
      capacity of the truncated polymerase to interact with TP was strongly reduced and
      its initiation activity was very low. On the other hand, its nucleotide binding
      affinity and its fidelity were not affected. We propose that the C-terminal 13
      amino acids of phi29 DNA polymerase are involved in DNA binding and in a stable
      interaction with the initiator protein TP, playing an important role in the
      intrinsic processivity of this enzyme during polymerization.

PMID- 14729921
TI  - Telomerase downregulation induced by the G-quadruplex ligand 12459 in A549 cells
      is mediated by hTERT RNA alternative splicing.
AB  - Ligand 12459, a potent G-quadruplex-interacting agent that belongs to the
      triazine series, was previously shown to downregulate telomerase activity in the
      human A549 lung carcinoma cell line. We show here that the downregulation of
      telomerase activity is caused by an alteration of the hTERT splicing pattern
      induced by 12459, i.e. an almost complete disappearance of the active
      (+alpha,+beta) transcript and an over-expression of the inactive -beta
      transcript. Spliced intron 6 forming the -beta hTERT transcript contained several
      tracks of G-rich sequences able to form G-quadruplexes. By using a specific PCR
      stop assay, we show that 12459 is able to stabilize the formation of these G
      quadruplex structures. A549 cell line clones selected for resistance to 12459
      have been analyzed for their hTERT splicing pattern. Resistant clones are able to
      maintain the active hTERT transcript under 12459 treatment, suggesting the
      appearance of mechanisms able to bypass the 12459-induced splicing alterations.
      In contrast to 12459, telomestatin and BRACO19, two other G-quadruplex
      interacting agents, have no effect on the hTERT splicing pattern in A549 cells,
      are cytotoxic against the A549-resistant clones and display a lower efficiency to
      stabilize hTERT G-quadruplexes. These results lead us to propose that 12459
      impairs the splicing machinery of hTERT through stabilization of quadruplexes
      located in the hTERT intron 6. Differences of selectivity between 12459, BRACO19
      and telomestatin for these hTERT quadruplexes may be important to explain their
      respective activity and inactivity against hTERT splicing.

PMID- 14729922
TI  - Local homology recognition and distance measures in linear time using compressed
      amino acid alphabets.
AB  - Methods for discovery of local similarities and estimation of evolutionary
      distance by identifying k-mers (contiguous subsequences of length k) common to
      two sequences are described. Given unaligned sequences of length L, these methods
      have O(L) time complexity. The ability of compressed amino acid alphabets to
      extend these techniques to distantly related proteins was investigated. The
      performance of these algorithms was evaluated for different alphabets and choices
      of k using a test set of 1848 pairs of structurally alignable sequences selected
      from the FSSP database. Distance measures derived from k-mer counting were found
      to correlate well with percentage identity derived from sequence alignments.
      Compressed alphabets were seen to improve performance in local similarity
      discovery, but no evidence was found of improvements when applied to distance
      estimates. The performance of our local similarity discovery method was compared
      with the fast Fourier transform (FFT) used in MAFFT, which has O(L log L) time
      complexity. The method for achieving comparable coverage to FFT is revealed here,
      and is more than an order of magnitude faster. We suggest using k-mer distance
      for fast, approximate phylogenetic tree construction, and show that a speed
      improvement of more than three orders of magnitude can be achieved relative to
      standard distance methods, which require alignments.

PMID- 14729923
TI  - CIRCE is not involved in heat-dependent transcription of groESL but in
      stabilization of the mRNA 5'-end in Rhodobacter capsulatus.
AB  - The CIRCE element, an inverted DNA repeat, is known to be involved in the
      temperature-dependent regulation of genes for heat shock proteins in a variety of
      organisms. The CIRCE element was identified as the target for the HrcA protein,
      which represses transcription of heat shock genes under normal growth
      temperature. Our data reveal that the CIRCE element is not involved in the
      temperature-dependent transcription of the groESL genes in Rhodobacter
      capsulatus. Apparently, R.capsulatus does not harbour an HrcA protein. The
      mechanisms of heat shock regulation of the groESL genes in R.capsulatus therefore
      diverge significantly from the regulatory pathway identified in other organisms.
      A structural analysis of the CIRCE RNA element revealed a stem of 11 nt pairs and
      a loop of only 5 nt. This folding differs from a structure with a 9 nt loop
      suggested previously on the basis of computer analysis. The RNA structure leads
      to a slight stabilization of the groESL mRNA that is more pronounced at normal
      growth temperature than under heat shock conditions.

PMID- 14729926
TI  - Lactoferricin influences early events of Listeria monocytogenes infection in THP
      1 human macrophages.
AB  - Bovine lactoferrin (BLf) and its derivative peptide lactoferricin B (LfcinB) are
      known for their antimicrobial activity towards several pathogens, including
      Listeria monocytogenes, a food-borne Gram-positive invasive bacterium that
      infects a wide variety of host cells, including professional phagocytes. To add
      further information on the antibacterial effects of these compounds, the
      influence of BLf, LfcinB and the antimicrobial centre of LfcinB, the hexapeptide
      LfcinB(4-9), on the invasive behaviour of L. monocytogenes was analysed in IFN
      gamma-activated human macrophagic cells (THP-1). Significant inhibition of
      bacterial entry in THP-1 cells was observed at LfcinB concentrations that were
      unable to produce any bacteriostatic or bactericidal effect, compared with BLf
      and LfcinB(4-9) peptide. This inhibition occurred when LfcinB was incubated
      during the bacterial infection step and was not due only to competition for
      common glycosaminoglycan receptors. Assays performed through a temperature shift
      from 4 to 37 degrees C showed that inhibition of invasion took place at an early
      post-adsorption step, although an effect on a different step of intracellular
      infection could not be ruled out.

PMID- 14729927
TI  - Chlorate: a reversible inhibitor of proteoglycan sulphation in Chlamydia
      trachomatis-infected cells.
AB  - Sulphated glycosaminoglycans, such as heparan sulphate, have been shown to be
      essential for the infectivity of many organisms. The aims of this study were to
      verify the role of sulphated glycosaminoglycans in chlamydial infection and to
      investigate whether they are present on chlamydia or chlamydial host cells. The
      effect of undersulphation of host cells and chlamydial elementary bodies was
      examined using sodium chlorate. Also studied was whether any inhibitory effect
      was reversible. The results strongly suggest that Chlamydia trachomatis does not
      produce heparan sulphate and that heparan sulphate of the host cell is necessary
      and sufficient to mediate chlamydial infection. The essential role played by the
      sulphate constituents of the host-cell glycosaminoglycan in the infectivity of
      LGV serovars, and to a lesser extent of serovar E, was also confirmed.

PMID- 14729924
TI  - Nucleotide incorporation by human DNA polymerase gamma opposite benzo[a]pyrene
      and benzo[c]phenanthrene diol epoxide adducts of deoxyguanosine and
      deoxyadenosine.
AB  - Mitochondria are major cellular targets of benzo[a]pyrene (BaP), a known
      carcinogen that also inhibits mitochondrial proliferation. Here, we report for
      the first time the effect of site-specific N2-deoxyguanosine (dG) and N6
      deoxyadenosine (dA) adducts derived from BaP 7,8-diol 9,10-epoxide (BaP DE) and
      dA adducts from benzo[c]phenanthrene 3,4-diol 1,2-epoxide (BcPh DE) on DNA
      replication by exonuclease-deficient human mitochondrial DNA polymerase (pol
      gamma) with and without the p55 processivity subunit. The catalytic subunit alone
      primarily misincorporated dAMP and dGMP opposite the BaP DE-dG adducts, and
      incorporated the correct dTMP as well as the incorrect dAMP opposite the DE-dA
      adducts derived from both BaP and BcPh. In the presence of p55 the polymerase
      incorporated all four nucleotides and catalyzed limited translesion synthesis
      past BaP DE-dG adducts but not past BaP or BcPh DE-dA adducts. Thus, all these
      adducts cause erroneous purine incorporation and significant blockage of further
      primer elongation. Purine misincorporation by pol gamma opposite the BaP DE-dG
      adducts resembles that observed with the Y family pol eta. Blockage of
      translesion synthesis by these DE adducts is consistent with known BaP inhibition
      of mitochondrial (mt)DNA synthesis and suggests that continued exposure to BaP
      reduces mtDNA copy number, increasing the opportunity for repopulation with pre
      existing mutant mtDNA and a resultant risk of mitochondrial genetic diseases.

PMID- 14729928
TI  - Protective effect of ethyl-3-(3-dimethyl aminopropyl)urea dihydrochloride (EDU)
      against LPS-induced death in mice.
AB  - Evaluation of anti-adhesive gels and bioresorbable films in animal models of
      intra-abdominal infection has shown that a product of the cross-linking reaction
      between hyaluronic acid (HA) and CM-cellulose, 1-ethyl-3-(3-dimethyl
      aminopropyl)urea dihydrochloride (EDU), has immunomodulatory properties. The
      effects of EDU were evaluated by using an endotoxin-induced shock mouse model.
      Pre-treatment of mice with EDU (50 mg kg(-1)) in DMSO resulted in a significant
      reduction in mortality following injection of LPS, compared to vehicle (DMSO) pre
      treatment alone. Serum levels of TNF-alpha, IL1beta and IFN-gamma in EDU-treated
      mice were significantly lower than those in vehicle-treated mice. Nitric oxide
      (NO) concentrations in the sera of mice after inoculation with LPS were
      significantly lower in the EDU-treated group than in the vehicle-treated group at
      various time-points. In contrast, EDU pre-treatment was associated with an
      enhanced IL10 response after LPS injection, compared to vehicle pre-treatment
      alone. In vitro studies revealed that IL10 production by RAW 264.7 macrophages,
      elicited by LPS, was increased significantly when EDU was added to the culture
      medium. These results suggest that the protective effect of EDU during LPS
      induced shock in mice is the result of inhibition of proinflammatory cytokines
      and NO production and an enhanced IL10 response.

PMID- 14729929
TI  - Lack of circulating Candida mannoprotein antigen in patients with focal
      hepatosplenic candidiasis.
AB  - The significance of Candida mannoprotein serum detection in 15 patients with
      haematological malignancies and proven (six cases) or probable (nine cases)
      hepatosplenic candidiasis was retrospectively evaluated. Circulating mannoprotein
      antigen was detected in three of six and in one of two serum samples from two
      patients with probable infection. The antigen was not detected in 38 serum
      samples of 13 (87%) patients. Thus, in contrast to other deep-seated Candida
      infections, mannoprotein is infrequently detectable during focal hepatosplenic
      candidiasis and does not appear to be of diagnostic value.

PMID- 14729930
TI  - Genotypic analysis of multidrug-resistant Mycobacterium tuberculosis isolates
      from Monterrey, Mexico.
AB  - Thirty-seven multidrug-resistant and 13 pan-susceptible isolates of Mycobacterium
      tuberculosis were analysed for the diversity of genotypes associated with known
      drug-resistance mechanisms. The isolates were obtained from patients attending a
      university tuberculosis clinic in Monterrey, Mexico. A total of 25 IS6110-RFLP
      patterns were obtained from the multidrug-resistant tuberculosis (MDR-TB)
      isolates. Approximately 65% of the MDR-TB isolates were attributed to secondary
      resistance. Different drug-susceptibility patterns were seen with the clustered
      isolates. The percentage of isolates resistant to isoniazid (INH), rifampicin
      (RIF), ethambutol (EMB) and streptomycin (STR) was 100, 97.3, 48.7 and 67.6,
      respectively. The most common resistance-associated polymorphisms for the four
      drugs were as follows: INH, Ser315Thr (67.6%) in katG; RIF, Ser450Leu (41.7%) in
      rpoB; EMB, Met306Ile/Val/Leu (66.7%) in embB; and STR, Lys43Arg (24%) in rpsL.
      Drug-resistance-associated mutations were similar to changes occurring in
      isolates from other areas of the world, but unique, previously unreported,
      mutations in katG (n=5), rpoB (n=1) and rrs (n=3) were also identified.

PMID- 14729931
TI  - Automation of a fluorescence-based multiplex PCR for the laboratory confirmation
      of common bacterial pathogens.
AB  - A fluorescence-based multiplex PCR was automated for the simultaneous detection
      of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in
      clinical samples from patients with suspected meningitis. Sensitivity of one to
      two genome copies per 100 microl sample and specificity of 100% for each organism
      were shown. Automation of DNA extraction, liquid handling, PCR and analysis are
      achieved on a single platform, which enables a high throughput and rapid
      turnaround of clinical samples that, in turn, leads to faster diagnosis. This is
      ultimately beneficial to the treatment of the patient and for public health
      management.

PMID- 14729932
TI  - Comparison of ITS and IGS1 regions for strain typing of clinical and non-clinical
      isolates of Pichia anomala.
AB  - Pichia anomala is an emerging nosocomial pathogen and there is a need for methods
      that distinguish between different P. anomala strains. In the typing of several
      clinical as well as non-clinical P. anomala strains, the sequence variation of
      the internal transcribed spacer (ITS) was found to be inadequate for typing
      purposes. The intergenic spacer 1 (IGS1) region of the rDNA of several P. anomala
      strains was therefore investigated in detail. The IGS1 region (which varied from
      1213 to 1231 bp in length) was interspersed with repeats and had more variation
      than the ITS regions. Comparative analysis in cases where analysis by the ITS was
      ambiguous clearly revealed the IGS1 region to be a more discriminatory tool in
      the typing of P. anomala strains.

PMID- 14729933
TI  - Human papillomavirus (HPV) study of 2916 cytological samples by PCR and DNA
      sequencing: genotype spectrum of patients from the west German area.
AB  - Human papillomaviruses (HPVs) are aetiological agents for cervical cancer. More
      than 70 different HPV types that infect genital mucosa have been found. In order
      to develop a sensitive and specific detection and typing assay, a PCR/direct
      sequencing approach was used. Two pairs of consensus primers were used for
      amplification of HPV DNA and the PCR products obtained were analysed by automated
      sequencing. Sequences were compared with those in GenBank by using the BLAST
      program. In this study, 2916 cytological samples were screened for HPV, as well
      as for triage. Nine hundred and forty-eight (32.5%) samples were positive for
      HPV, of which 134 harboured more than one HPV type. Of the 948 PCR-positive
      samples, 648 were typed. Thirty-nine different HPV types were identified by
      sequencing. The two most frequently found HPV types, 16 and 31, together
      accounted for 36.3% of the sequences (26.2 and 10.1%, respectively). This group
      was followed by HPV types 6 (5.7%), 18 (5.3%), 58 (4.5%), 61 (4.5%), 53 (4.4%),
      42 (4.3%) and 51 (4.0%). All other types were detected at frequencies <4% and
      eight types were detected only once. PCR/direct sequencing is a reliable method
      for routine detection of HPV in cytological samples. The data presented here
      suggest a complex distribution of HPV types in the population tested. The results
      accentuate the importance of PCR-based techniques in HPV diagnosis, as
      hybridization-based methods can only detect a limited number of infections. This
      method can also be applied easily to the analysis of tissue samples and it
      therefore also allows type-specific follow-up of women who have been treated for
      cervical intraepithelial neoplasia.

PMID- 14729934
TI  - Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered
      from treated patients.
AB  - Two-hundred sequential Aspergillus fumigatus isolates recovered from 26
      immunocompromised patients with invasive aspergillosis or bronchial colonization
      were tested for their in vitro susceptibility to posaconazole, itraconazole,
      voriconazole, terbinafine and amphotericin B. Twenty-one patients were treated
      with amphotericin B and/or itraconazole. Antifungal susceptibilities of the
      isolates recovered before treatment were not significantly different from those
      of isolates recovered after the onset of antifungal therapy. The highest MICs
      were 0.125, 0.5, 0.5, 1 and 1 microg ml(-1) for posaconazole, itraconazole,
      voriconazole, terbinafine and amphotericin B, respectively. It is concluded that
      the emergence of resistance in A. fumigatus during antifungal therapy with
      amphotericin B or itraconazole is an uncommon phenomenon.

PMID- 14729935
TI  - Frameshift mutations in frxA occur frequently and do not provide a reliable
      marker for metronidazole resistance in UK isolates of Helicobacter pylori.
AB  - Mutations in the NAD(P)H flavin oxidoreductase gene (frxA) are thought to
      contribute to the development of metronidazole resistance in Helicobacter pylori.
      To test this further, 44 frxA sequences in 18 patient isolate sets of H. pylori
      were examined including a unique collection comprising separated Mtz-sensitive
      (MtzS) and Mtz-resistant (MtzR) subpopulations pre-treatment and matched MtzR
      strains post-treatment. Sequences of frxA contained frameshift mutations that led
      to premature protein truncation in at least one strain from most (17/18) patient
      sets. These mutations were present in all strains, irrespective of Mtz
      resistotype in 13/18 patients. Frameshift due to a single adenine deletion at
      nucleotide 53 was the most common mutation and was present in isolates from 11/18
      patients. A novel real-time (LightCycler) PCR-based probe hybridization melting
      point assay applied to a further 119 isolates confirmed that the frameshift-53
      mutation occurred frequently, in 20% of isolates, and could be present in MtzS as
      well as MtzR strains (42% vs 58%). This study demonstrates that frameshift
      mutations occur in MtzS strains as well as in MtzR strains, and are thus unlikely
      to cause Mtz resistance.

PMID- 14729936
TI  - Parvovirus B19 infection in medical students during a hospital outbreak.
AB  - From March to May 2002, a parvovirus B19 (B19) outbreak was identified at a
      general hospital that serves as a teaching facility for the Universidad Autonoma
      de San Luis Potosi, Mexico. Medical students attending the hospital presented
      with symptoms suggestive of B19 infection. Previous studies have suggested that
      apparent hospital-related B19 outbreaks may be a reflection of B19 infection in
      the community. A study was undertaken to assess whether exposure to the hospital
      was a risk factor for B19 infection and to determine to what extent medical
      students were infected during this outbreak. The incidence of B19 infection in
      medical students attending the teaching hospital during the outbreak (n=211) was
      determined and compared to students not attending the hospital (n=96). To assess
      if a community-wide outbreak had occurred, 80 blood donors were also evaluated
      for the presence of B19 antibodies. Acute B19 infection was identified in 40 of
      119 (33.6%) susceptible students attending the hospital and in 20 of 47 (42.6%)
      susceptible students not attending the hospital. The frequency of acute infection
      among susceptible blood donors was lower (9.5%) than in students, but higher than
      the rate expected during non-epidemic periods. Most infections (68.3%) were
      asymptomatic. Symptoms reported by infected subjects were not specific for B19
      infection. Only 11.7% of subjects with acute infection fulfilled the clinical
      surveillance definition used to detect cases during the outbreak. In conclusion,
      hospital exposure was not associated to increased risk of B19 infection among
      medical students. Medical students may be at increased risk for acquiring and
      transmitting B19 infection during outbreaks.

PMID- 14729937
TI  - Long-term predominance of two pan-European clones among multi-resistant
      Acinetobacter baumannii strains in the Czech Republic.
AB  - In a recent study, a large proportion of multi-drug-resistant (MDR) Acinetobacter
      baumannii strains that were isolated from hospitalized patients in the Czech
      Republic was found to belong to two major groups (A and B). These groups appeared
      to be similar to epidemic clones I and II, respectively, which were identified
      previously among outbreak strains from north-western European hospitals. The aim
      of the present study was to assess in detail the genetic relatedness of Czech A.
      baumannii strains and those of epidemic clones I and II by using ribotyping with
      HindIII and HincII and by AFLP fingerprinting. The study collection included 70
      MDR strains that were isolated in 30 Czech hospitals in 1991-2001, 15 susceptible
      Czech strains from 1991 to 1996 and 13 reference strains of clones I and II from
      1982 to 1990. One major HindIII/HincIII ribotype (R1-1) was observed in 38 MDR
      Czech strains and eight reference strains of clone I, whereas another major
      ribotype (R2-2) was observed in 11 MDR Czech strains and in three reference
      strains of clone II. A selection of 59 Czech strains (representative of all
      ribotypes) and the 13 reference strains were investigated by AFLP fingerprinting.
      At a clustering level of 83%, two large clusters could be distinguished: cluster
      1 included all reference strains of clone I and 25 MDR Czech strains, whilst
      cluster 2 contained all reference strains of clone II and 11 MDR Czech strains.
      There was a clear correlation between the groupings by AFLP analysis and by
      ribotyping, as all strains with ribotype R1-1 and four strains with slightly
      different ribotypes were found in AFLP cluster 1, whereas all strains with
      ribotype R2-2 and seven strains with similar ribotypes were in AFLP cluster 2.
      Thus, 41 and 21 MDR Czech strains could be classified as belonging to clones I
      and II, respectively. The remaining eight MDR and 15 susceptible strains were
      highly heterogeneous and were distinct from clones I and II by both AFLP
      fingerprinting and ribotyping. These results indicate that the two predominant
      groups observed among MDR Czech A. baumannii strains from the 1990s are
      genetically congruent with the north-western European epidemic clones that were
      found in the 1980s. Recognition of these clinically relevant, widespread clones
      is important in infection prevention and control; they are also interesting
      subjects to study genetic mechanisms that give rise to their antibiotic
      resistance and epidemic behaviour.

PMID- 14729939
TI  - Clonal similarity of salivary and nasopharyngeal Fusobacterium nucleatum in
      infants with acute otitis media experience.
AB  - The environment of an infant's nasopharynx during acute otitis media (AOM)
      favours the growth of anaerobic bacteria, which can be recovered frequently
      during infection, but hardly at all if the infant is healthy. The aim of this
      investigation was to identify the potential source and inoculation route of
      anaerobes that were present in the nasopharynx. Eleven Fusobacterium nucleatum
      isolates that were collected through the nasal cavity from the nasopharynx of
      eight infants with a history of AOM, and 161 F. nucleatum isolates from the
      saliva of the same infants, were typed to the clonal level by using arbitrarily
      primed PCR (AP-PCR). In five of the eight infants examined, identical AP-PCR
      types were found among nasopharyngeal and salivary isolates. As anaerobes seem to
      be present only transiently in the nasopharynx and salivary contamination of the
      nasopharyngeal samples can be excluded, this observation indicates that the
      source of nasopharyngeal anaerobes is the oral cavity and that saliva is their
      transmission vehicle.

PMID- 14729938
TI  - Mycobacterium tuberculosis isolates belonging to katG gyrA group 2 are associated
      with clustered cases of tuberculosis in Italian patients.
AB  - Fifty-one consecutive isolates of Mycobacterium tuberculosis, collected during a
      2-year period in the north-east of Italy, were subjected to IS6110-RFLP analysis
      to detect the presence of clusters and assigned to one of the three genotypic
      groups delineated by single nucleotide polymorphisms in the genes katG and gyrA.
      All the isolates collected from the local population belonged to group 2 or 3,
      while group 1 isolates were found only in specimens collected from African
      immigrants. Clustered cases of tuberculosis, which are likely to be related to
      recently transmitted infection, were found to be significantly associated with
      katG gyrA group 2. In the local situation, strains belonging to this group may
      therefore present a higher risk of transmission.

PMID- 14729940
TI  - Clostridium difficile colonization in healthy adults: transient colonization and
      correlation with enterococcal colonization.
AB  - The aim of the present study was to investigate the colonization status of
      Clostridium difficile in healthy individuals. In total, 139 healthy adults from
      two study groups were examined at intervals of 3 months. Among the 18 positive
      subjects, the number of subjects from whom C. difficile was isolated once, twice,
      three times or four times was 10 (55.6%), three (16.7%), two (11.1%) and three
      (16.7%), respectively. In the student group, different subjects were colonized by
      different PCR ribotype/PFGE types. However, the same PCR ribotype/PFGE types of
      C. difficile were isolated from different subjects in the employee group,
      indicating that cross-transmission may have occurred in this group. Continuous
      colonization by the same PCR ribotype/PFGE type was only observed in three
      subjects. C. difficile-positive subjects were significantly more densely
      colonized by enterococci (P<0.05) than C. difficile-negative subjects: subjects
      that were found to be C. difficile-positive three or four times appeared to have
      higher concentrations of enterococci. The present results demonstrate that,
      although colonization by a C. difficile strain is transient in many cases, there
      are healthy individuals that are colonized persistently by C. difficile. They
      also suggest that dense colonization of the intestine by enterococci may be
      associated with C. difficile colonization.

PMID- 14729941
TI  - False-positive result with BinaxNOW Legionella Antigen immunochromatographic
      (ICT) assay: response to Helbig et al. (2001).

PMID- 14729942
TI  - Identification of phosphoproteins and their phosphorylation sites in the WEHI-231
      B lymphoma cell line.
AB  - A major goal of the Alliance for Cellular Signaling is to elaborate the
      components of signal transduction networks in model cell systems, including
      murine B lymphocytes. Due to the importance of protein phosphorylation in many
      aspects of cell signaling, the initial efforts have focused on the identification
      of phosphorylated proteins. In order to identify serine- and threonine
      phosphorylated proteins on a proteome-wide basis, WEHI-231 cells were treated
      with calyculin A, a serine/threonine phosphatase inhibitor, to induce high levels
      of protein phosphorylation. Proteins were extracted from whole-cell lysates and
      digested with trypsin. Phosphorylated peptides were then enriched using
      immobilized metal affinity chromatography and identified by liquid chromatography
      tandem mass spectrometry. A total of 107 proteins and 193 phosphorylation sites
      were identified using these methods. Forty-two of these proteins have been
      reported to be phosphorylated, but only some of them have been detected in B
      cells. Fifty-four of the identified proteins were not previously known to be
      phosphorylated. The remaining 11 phosphoproteins have previously only been
      characterized as novel cDNA or genomic sequences. Many of the identified proteins
      were phosphorylated at multiple sites. The proteins identified in this study
      significantly expand the repertoire of proteins known to be phosphorylated in B
      cells. The number of newly identified phosphoproteins indicates that B cell
      signaling pathways utilizing protein phosphorylation are likely to be more
      complex than previously appreciated.

PMID- 14729943
TI  - RNase MRP cleaves the CLB2 mRNA to promote cell cycle progression: novel method
      of mRNA degradation.
AB  - RNase mitochondrial RNA processing (RNase MRP) mutants have been shown to have an
      exit-from-mitosis defect that is caused by an increase in CLB2 mRNA levels,
      leading to increased Clb2p (B-cyclin) levels and a resulting late anaphase delay.
      Here we describe the molecular defect behind this delay. CLB2 mRNA normally
      disappears rapidly as cells complete mitosis, but the level remains high in RNase
      MRP mutants. This is in direct contrast to other exit-from-mitosis mutants and is
      the result of an increase in CLB2 mRNA stability. We found that highly purified
      RNase MRP cleaved the 5' untranslated region (UTR) of the CLB2 mRNA in several
      places in an in vitro assay. In vivo, we identified RNase MRP-dependent cleavage
      products on the CLB2 mRNA that closely matched in vitro products. Disposal of
      these products was dependent on the 5'-->3' exoribonuclease Xrn1 and not the
      exosome. Our results demonstrate that the endoribonuclease RNase MRP specifically
      cleaves the CLB2 mRNA in its 5'-UTR to allow rapid 5' to 3' degradation by the
      Xrn1 nuclease. Degradation of the CLB2 mRNA by the RNase MRP endonuclease
      provides a novel way to regulate the cell cycle that complements the protein
      degradation machinery. In addition, these results denote a new mechanism of mRNA
      degradation not seen before in the yeast Saccharomyces cerevisiae.

PMID- 14729944
TI  - Iron-mediated degradation of IRP2, an unexpected pathway involving a 2
      oxoglutarate-dependent oxygenase activity.
AB  - Iron regulatory protein 2 (IRP2), a central posttranscriptional regulator of
      cellular and systemic iron metabolism, undergoes proteasomal degradation in iron
      replete cells. The prevailing model postulates that the mechanism involves site
      specific oxidation of 3 cysteine residues (C168, C174, and C178) within a 73
      amino-acid (73-aa) degradation domain. By expressing wild-type and mutated
      versions of IRP2 in H1299 cells, we find that a C168S C174S C178S triple mutant,
      or a deletion mutant lacking the entire "73-aa domain," is sensitive to iron
      mediated degradation, like wild-type IRP2. The antioxidants N-acetylcysteine,
      ascorbate, and alpha-tocopherol not only fail to stabilize IRP2 but, furthermore,
      promote its proteasomal degradation. The pathway for IRP2 degradation is
      saturable, which may explain earlier data supporting the "cysteine oxidation
      model," and shows remarkable similarities with the degradation of the hypoxia
      inducible factor 1 alpha (HIF-1 alpha): dimethyl-oxalylglycine, a specific
      inhibitor of 2-oxoglutarate-dependent oxygenases, stabilizes IRP2 following the
      administration of iron to iron-deficient cells. Our results challenge the current
      model for IRP2 regulation and provide direct pharmacological evidence for the
      involvement of 2-oxoglutarate-dependent oxygenases in a pathway for IRP2
      degradation.

PMID- 14729945
TI  - Regulation of phosphoinositide 3-kinase by its intrinsic serine kinase activity
      in vivo.
AB  - One potentially important mechanism for regulating class Ia phosphoinositide 3
      kinase (PI 3-kinase) activity is autophosphorylation of the p85 alpha adapter
      subunit on Ser608 by the intrinsic protein kinase activity of the p110 catalytic
      subunit, as this downregulates the lipid kinase activity in vitro. Here we
      investigate whether this phosphorylation can occur in vivo. We find that p110
      alpha phosphorylates p85 alpha Ser608 in vivo with significant stoichiometry.
      However, p110 beta is far less efficient at phosphorylating p85 alpha Ser608,
      identifying a potential difference in the mechanisms by which these two isoforms
      are regulated. The p85 alpha Ser608 phosphorylation was increased by treatment
      with insulin, platelet-derived growth factor, and the phosphatase inhibitor
      okadaic acid. The functional effects of this phosphorylation are highlighted by
      mutation of Ser608, which results in reduced lipid kinase activity and reduced
      association of the p110 alpha catalytic subunit with p85 alpha. The importance of
      this phosphorylation was further highlighted by the finding that
      autophosphorylation on Ser608 was impaired, while lipid kinase activity was
      increased, in a p85 alpha mutant recently discovered in human tumors. These
      results provide the first evidence that phosphorylation of Ser608 plays a role as
      a shutoff switch in growth factor signaling and contributes to the differences in
      functional properties of different PI 3-kinase isoforms in vivo.

PMID- 14729946
TI  - Phosphorylation of serine 18 regulates distinct p53 functions in mice.
AB  - The p53 protein acts a tumor suppressor by inducing cell cycle arrest and
      apoptosis in response to DNA damage or oncogene activation. Recently, it has been
      proposed that phosphorylation of serine 15 in human p53 by ATM (mutated in ataxia
      telangiectasia) kinase induces p53 activity by interfering with the Mdm2-p53
      complex formation and inhibiting Mdm2-mediated destabilization of p53. Serine 18
      in murine p53 has been implicated in mediating an ATM- and ataxia telangiectasia
      related kinase-dependent growth arrest. To explore further the physiological
      significance of phosphorylation of p53 on Ser18, we generated mice bearing a
      serine-to-alanine mutation in p53. Analysis of apoptosis in thymocytes and
      splenocytes following DNA damage revealed that phosphorylation of serine 18 was
      required for robust p53-mediated apoptosis. Surprisingly, p53Ser18
      phosphorylation did not alter the proliferation rate of embryonic fibroblasts or
      the p53-mediated G(1) arrest induced by DNA damage. In addition, endogenous basal
      levels and DNA damage-induced levels of p53 were not affected by p53Ser18
      phosphorylation. p53Ala18 mice developed normally and were not susceptible to
      spontaneous tumorigenesis, and the reduced apoptotic function of p53Ala18 did not
      rescue the embryo-lethal phenotype of Mdm2-null mice. These results indicate that
      phosphorylation of the ATM target site on p53 specifically regulates p53
      apoptotic function and further reveal that phosphorylation of p53 serine 18 is
      not required for p53-mediated tumor suppression.

PMID- 14729947
TI  - Physical and functional interactions of the Arf tumor suppressor protein with
      nucleophosmin/B23.
AB  - The Arf tumor suppressor inhibits cell cycle progression through both p53
      dependent and p53-independent mechanisms, including interference with rRNA
      processing. Using tandem-affinity-tagged p19(Arf), we purified Arf-associated
      proteins from mouse NIH 3T3 fibroblasts undergoing cell cycle arrest. Tagged
      p19(Arf) associated with nucleolar and ribosomal proteins, including
      nucleophosmin/B23 (NPM), a protein thought to foster the maturation of
      preribosomal particles. NPM is an abundant protein, only a minor fraction of
      which binds to p19(Arf); however, a significant proportion of p19(Arf) associates
      with NPM. The interaction between p19(Arf) and NPM requires amino acid sequences
      at the Arf amino terminus, which are also required for Mdm2 binding, as well as
      the central acidic domain of NPM and an adjacent segment that regulates NPM
      oligomerization. The interaction between p19(Arf) and NPM occurs in primary mouse
      embryonic fibroblasts, including those lacking both Mdm2 and p53. In an NIH 3T3
      derivative cell line (MT-Arf) engineered to conditionally express an Arf
      transgene, induced p19(Arf) associates with NPM and colocalizes with it in high
      molecular-weight complexes (2 to 5 MDa). An NPM mutant lacking its carboxyl
      terminal nucleic acid-binding domain oligomerizes with endogenous NPM, inhibits
      p19(Arf) from entering into 2- to 5-MDa particles, and overrides the ability of
      p19(Arf) to retard rRNA processing.

PMID- 14729948
TI  - APRIL-deficient mice have normal immune system development.
AB  - APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor
      (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of
      different origin and a low level of expression in normal cells. APRIL shares two
      TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF.
      BLyS is involved in regulation of B-cell activation and survival and also binds
      to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant
      APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency
      results in severe B-cell dysfunction. To investigate the physiological role of
      APRIL, we generated mice that are deficient in its encoding gene. APRIL(-/-) mice
      were viable and fertile and lacked any gross abnormality. Detailed histological
      analysis did not reveal any defects in major tissues and organs, including the
      primary and secondary immune organs. T- and B-cell development and in vitro
      function were normal as well, as were T-cell-dependent and -independent in vivo
      humoral responses to antigenic challenge. These data indicate that APRIL is
      dispensable in the mouse for proper development. Thus, BLyS may be capable of
      fulfilling APRIL's main functions.

PMID- 14729949
TI  - Suppression of PTEN expression by NF-kappa B prevents apoptosis.
AB  - NF-kappa B is a heterodimeric transcription activator consisting of the DNA
      binding subunit p50 and the transactivation subunit p65/RelA. NF-kappa B prevents
      cell death caused by tumor necrosis factor (TNF) and other genotoxic insults by
      directly inducing antiapoptotic target genes. We report here that the tumor
      suppressor PTEN, which functions as a negative regulator of phosphatidylinositol
      (PI)-3 kinase/Akt-mediated cell survival pathway, is down regulated by p65 but
      not by p50. Moreover, a subset of human lung or thyroid cancer cells expressing
      high levels of endogenous p65 showed decreased expression of PTEN that could be
      rescued by specific inhibition of the NF-kappa B pathway with I kappa B
      overexpression as well as with small interfering RNA directed against p65.
      Importantly, TNF, a potent inducer of NF-kappa B activity, suppressed PTEN gene
      expression in IKK beta(+/+) cells but not in IKK beta(-/-) cells, which are
      deficient in the NF-kappa B activation pathway. These findings indicated that NF
      kappa B activation was necessary and sufficient for inhibition of PTEN
      expression. The promoter, RNA, and protein levels of PTEN are down-regulated by
      NF-kappa B. The mechanism underlying suppression of PTEN expression by NF-kappa B
      was independent of p65 DNA binding or transcription function and involved
      sequestration of limiting pools of transcriptional coactivators CBP/p300 by p65.
      Restoration of PTEN expression inhibited NF-kappa B transcriptional activity and
      augmented TNF-induced apoptosis, indicating a negative regulatory loop involving
      PTEN and NF-kappa B. PTEN is, thus, a novel target whose suppression is critical
      for antiapoptosis by NF-kappa B.

PMID- 14729950
TI  - Embryonic lethality, decreased erythropoiesis, and defective octamer-dependent
      promoter activation in Oct-1-deficient mice.
AB  - Oct-1 is a sequence-specific DNA binding transcription factor that is believed to
      regulate a large group of tissue-specific and ubiquitous genes. Both Oct-1 and
      the related but tissue-restricted Oct-2 protein bind to a DNA sequence termed the
      octamer motif (5'-ATGCAAAT-3') with equal affinity in vitro. To address the role
      of Oct-1 in vivo, an Oct-1-deficient mouse strain was generated by gene
      targeting. Oct-1-deficient embryos died during gestation, frequently appeared
      anemic, and suffered from a lack of Ter-119-positive erythroid precursor cells.
      This defect was cell intrinsic. Fibroblasts derived from these embryos displayed
      a dramatic decrease in Oct-1 DNA binding activity and a lack of octamer-dependent
      promoter activity in transient transfection assays. Interestingly, several
      endogenous genes thought to be regulated by Oct-1 showed no change in expression.
      When crossed to Oct-2(+/-) animals, transheterozygotes were recovered at a very
      low frequency. These findings suggest a critical role for Oct-1 during
      development and a stringent gene dosage effect with Oct-2 in mediating postnatal
      survival.

PMID- 14729951
TI  - The corepressor mSin3A regulates phosphorylation-induced activation, intranuclear
      location, and stability of AML1.
AB  - The AML1 (RUNX1) gene, one of the most frequent targets of translocations
      associated with human leukemias, encodes a DNA-binding protein that plays pivotal
      roles in myeloid differentiation through transcriptional regulation of various
      genes. Previously, we reported that AML1 is phosphorylated on two serine residues
      with dependence on activation of extracellular signal-regulated kinase, which
      positively regulates the transcriptional activity of AML1. Here, we demonstrate
      that the interaction between AML1 and the corepressor mSin3A is regulated by
      phosphorylation of AML1 and that release of AML1 from mSin3A induced by
      phosphorylation activates its transcriptional activity. Furthermore,
      phosphorylation of AML1 regulates its intranuclear location and disrupts
      colocalization of AML1 with mSin3A in the nuclear matrix. PEBP2 beta/CBF beta, a
      heterodimeric partner of AML1, was shown to play a role in protecting AML1 from
      proteasome-mediated degradation. We show that mSin3A also protects AML1 from
      proteasome-mediated degradation and that phosphorylation-induced release of AML1
      from mSin3A results in degradation of AML1 in a time-dependent manner. This study
      provides a novel regulatory mechanism for the function of transcription factors
      mediated by protein modification and interaction with cofactors.

PMID- 14729952
TI  - ARA67/PAT1 functions as a repressor to suppress androgen receptor
      transactivation.
AB  - The androgen receptor (AR) may recruit multiple coregulators for proper or
      optimal transactivation. Here we report the identification and characterization
      of ARA67/PAT1 as an AR coregulator from a prostate cDNA library. ARA67/PAT1 was
      screened out as an AR N terminus interacting protein. Interaction mapping shows
      that the cooperation of multiple domains within ARA67/PAT1 may be required for
      the maximal interaction with AR. ARA67/PAT1 functions as a repressor with better
      suppressive effects on AR compared to glucocorticoid receptor and estrogen
      receptor. Further mechanism dissection reveals that the interrupted AR
      cytoplasmic-nuclear shuttling may play a major role in ARA67/PAT1 mediated
      suppression on AR. Together, these results suggest that ARA67/PAT1 may function
      as a novel repressor that can modulate AR function in prostate cancer.

PMID- 14729953
TI  - Identification of MoKA, a novel F-box protein that modulates Kruppel-like
      transcription factor 7 activity.
AB  - KLF7, a member of the Kruppel-like transcription factor family, is believed to
      regulate neurogenesis and cell cycle progression. Here, a yeast two-hybrid screen
      for KLF7 cofactors in the developing nervous system identified a novel 140-kDa
      protein named MoKA, for modulator of KLF7 activity. Interaction between MoKA and
      KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and
      by coimmunoprecipitation of the proteins overexpressed in mammalian cells.
      Functional assays documented that MoKA is a KLF7 coactivator, and in situ
      hybridizations identified the developing nervous system and the adult testes as
      two sites of MoKA and Klf7 coexpression. Chromatin immunoprecipitation
      experiments demonstrated KLF7 binding to the p21(WAF1/Cip1) gene while transient
      transfection assays documented KLF7 stimulation of the p21(WAF1/Cip1) proximal
      promoter. Additional tests revealed that distinct structural motifs of MoKA
      direct interaction with KLF7 and shuttling between the nucleus and cytoplasm of
      asynchronously cycling cells. Altogether, our results strongly suggest that MoKA
      and KLF7 interact functionally to regulate gene expression during cell
      differentiation and identify the cell cycle regulator p21(WAF1/Cip1) as one of
      the targeted genes.

PMID- 14729954
TI  - Novel isotypic gamma/zeta subunits reveal three coatomer complexes in mammals.
AB  - In early secretory transport, coat recruitment for the formation of coat protein
      I (COPI) vesicles involves binding to donor Golgi membranes of the small GTPase
      ADP-ribosylation factor 1 and subsequent attachment of the cytoplasmic heptameric
      complex coatomer. Various hypotheses exist as to the precise role of and possible
      routes taken by COPI vesicles in the mammalian cell. Here we report the
      ubiquitous expression of two novel isotypes of coatomer subunits gamma- and zeta
      COP that are incorporated into coatomer, and show that three isotypes exist of
      the complex defined by the subunit combinations gamma 1/zeta 1, gamma 1/zeta 2,
      and gamma 2/zeta 1. In a liver cytosol, these forms make up the total coatomer in
      a ratio of about 2:1:2, respectively. The coatomer isotypes are located
      differentially within the early secretory pathway, and the gamma 2/zeta 1 isotype
      is preferentially incorporated into COPI vesicles. A population of COPI vesicles
      was characterized that almost exclusively contains gamma 2/zeta 1 coatomer. This
      existence of three structurally different forms of coatomer will need to be
      considered in future models of COPI-mediated transport.

PMID- 14729955
TI  - Extracellular signal-regulated kinase 2 interacts with and is negatively
      regulated by the LIM-only protein FHL2 in cardiomyocytes.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathway regulates diverse
      biologic functions including cell growth, differentiation, proliferation, and
      apoptosis. The extracellular signal-regulated kinases (ERKs) constitute one
      branch of the MAPK pathway that has been implicated in the regulation of cardiac
      differentiated growth, although the downstream mechanisms whereby ERK signaling
      affects this process are not well characterized. Here we performed a yeast two
      hybrid screen with ERK2 bait and a cardiac cDNA library to identify novel
      proteins involved in regulating ERK signaling in cardiomyocytes. This screen
      identified the LIM-only factor FHL2 as an ERK interacting protein in both yeast
      and mammalian cells. In vivo, FHL2 and ERK2 colocalized in the cytoplasm at the
      level of the Z-line, and interestingly, FHL2 interacted more efficiently with the
      activated form of ERK2 than with the dephosphorylated form. ERK2 also interacted
      with FHL1 and FHL3 but not with the muscle LIM protein. Moreover, at least two
      LIM domains in FHL2 were required to mediate efficient interaction with ERK2. The
      interaction between ERK2 and FHL2 did not influence ERK1/2 activation, nor was
      FHL2 directly phosphorylated by ERK2. However, FHL2 inhibited the ability of
      activated ERK2 to reside within the nucleus, thus blocking ERK-dependent
      transcriptional responsiveness of ELK-1, GATA4, and the atrial natriuretic factor
      promoter. Finally, FHL2 partially antagonized the cardiac hypertrophic response
      induced by activated MEK-1, GATA4, and phenylephrine agonist stimulation.
      Collectively, these results suggest that FHL2 serves a repressor function in
      cardiomyocytes through its ability to inhibit ERK1/2 transcriptional coupling.

PMID- 14729956
TI  - Evidence for a conserved function in synapse formation reveals Phr1 as a
      candidate gene for respiratory failure in newborn mice.
AB  - Genetic studies using a set of overlapping deletions centered at the piebald
      locus on distal mouse chromosome 14 have defined a genomic region associated with
      respiratory distress and lethality at birth. We have isolated and characterized
      the candidate gene Phr1 that is located within the respiratory distress critical
      genomic interval. Phr1 is the ortholog of the human Protein Associated with Myc
      as well as Drosophila highwire and Caenorhabditis elegans regulator of
      presynaptic morphology 1. Phr1 is expressed in the embryonic and postnatal
      nervous system. In mice lacking Phr1, the phrenic nerve failed to completely
      innervate the diaphragm. In addition, nerve terminal morphology was severely
      disrupted, comparable with the synaptic defects seen in the Drosophila hiw and C.
      elegans rpm-1 mutants. Although intercostal muscles were completely innervated,
      they also showed dysmorphic nerve terminals. In addition, sensory neuron
      terminals in the diaphragm were abnormal. The neuromuscular junctions showed
      excessive sprouting of nerve terminals, consistent with inadequate presynaptic
      stimulation of the muscle. On the basis of the abnormal neuronal morphology seen
      in mice, Drosophila, and C. elegans, we propose that Phr1 plays a conserved role
      in synaptic development and is a candidate gene for respiratory distress and
      ventilatory disorders that arise from defective neuronal control of breathing.

PMID- 14729957
TI  - Recognition of phosphorylated-Smad2-containing complexes by a novel Smad
      interaction motif.
AB  - Transforming growth factor beta (TGF-beta) superfamily members signal via
      complexes of activated Smads, comprising phosphorylated receptor-regulated Smads,
      such as Smad2 and Smad3, and Smad4. These complexes are recruited to DNA by
      specific transcription factors. The forkhead/winged-helix transcription factors,
      XFast-1/XFoxH1a and XFast-3/XFoxH1b, bind an activated Smad heterotrimer
      comprising two Smad2s and one Smad4. Here we identify a novel Smad2 interaction
      motif, the Fast/FoxH1 motif (FM), present in all known Fast/FoxH1 family members,
      N-terminal to the common Smad interaction motif (SIM). The FM is necessary and
      sufficient to bind active Smad2/Smad4 complexes. The FM differs from the SIM
      since it discriminates between Smad2 and Smad3, and moreover only binds
      phosphorylated Smad2 in the context of activated Smad complexes. It is the first
      Smad interaction motif with this property. Site-directed mutagenesis indicates
      that the binding site for the FM on a Smad2/Smad4 heterotrimer is a hydrophobic
      pocket that incorporates the Smad/Smad interface. We demonstrate that the
      presence of an FM and SIM in the Fast/FoxH1 proteins allows them to compete
      efficiently for activated Smad2/Smad4 complexes with transcription factors such
      as Mixer that only contain a SIM. This establishes a hierarchy of Smad
      interacting transcription factors, determined by their affinity for active Smad
      complexes.

PMID- 14729958
TI  - Photo-cross-linking of a purified preinitiation complex reveals central roles for
      the RNA polymerase II mobile clamp and TFIIE in initiation mechanisms.
AB  - The topological organization of a TATA binding protein-TFIIB-TFIIF-RNA polymerase
      II (RNAP II)-TFIIE-promoter complex was analyzed using site-specific protein-DNA
      photo-cross-linking of gel-purified complexes. The cross-linking results for the
      subunits of RNAP II were used to determine the path of promoter DNA against the
      structure of the enzyme. The results indicate that promoter DNA wraps around the
      mobile clamp of RNAP II. Cross-linking of TFIIF and TFIIE both upstream of the
      TATA element and downstream of the transcription start site suggests that both
      factors associate with the RNAP II mobile clamp. TFIIE alpha closely approaches
      promoter DNA at nucleotide -10, a position immediately upstream of the
      transcription bubble in the open complex. Increased stimulation of transcription
      initiation by TFIIE alpha is obtained when the DNA template is artificially
      premelted in the -11/-1 region, suggesting that TFIIE alpha facilitates open
      complex formation, possibly through its interaction with the upstream end of the
      partially opened transcription bubble. These results support the central roles of
      the mobile clamp of RNAP II and TFIIE in transcription initiation.

PMID- 14729959
TI  - The tumor suppressor p53 inhibits Net, an effector of Ras/extracellular signal
      regulated kinase signaling.
AB  - The tumor suppressor function of p53 is linked to its ability to repress gene
      expression, but the mechanisms of specific gene repression are poorly understood.
      We report that wild-type p53 inhibits an effector of the Ras oncogene/mitogen
      activated protein (MAP) kinase pathway, the transcription factor Net. Tumor
      associated mutant p53s are less efficient inhibitors. p53 inhibits by preventing
      phosphorylation of Net by MAP kinases. Loss of p53 in vivo leads to increased Net
      phosphorylation in response to wound healing and UV irradiation of skin. Our
      results show that p53 can repress specific gene expression by inhibiting Net, a
      factor implicated in cell cycle entry.

PMID- 14729960
TI  - The Drosophila poly(A) binding protein-interacting protein, dPaip2, is a novel
      effector of cell growth.
AB  - The 3' poly(A) tail of eukaryotic mRNAs and the poly(A) binding protein (PABP)
      play important roles in the regulation of translation. Recently, a human PABP
      interacting protein, Paip2, which disrupts the PABP-poly(A) interaction and
      consequently inhibits translation, was described. To gain insight into the
      biological role of Paip2, we studied the Drosophila melanogaster Paip2 (dPaip2).
      dPaip2 is the bona fide human Paip2 homologue, as it interacts with dPABP,
      inhibits binding of dPABP to the mRNA poly(A) tail, and reduces translation of a
      reporter mRNA by approximately 80% in an S2 cell-free translation extract.
      Ectopic overexpression of dPaip2 in Drosophila wings and wing discs results in a
      size reduction phenotype, which is due to a decrease in cell number. Clones of
      cells overexpressing dPaip2 in wing discs also contain fewer cells than controls.
      This phenotype can be explained by a primary effect on cell growth. Indeed,
      overexpression of dPaip2 in postreplicative tissues inhibits growth, inasmuch as
      it reduces ommatidia size in eyes and cell size in the larval fat body. We
      conclude that dPaip2 inhibits cell growth primarily by inhibiting protein
      synthesis.

PMID- 14729961
TI  - RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the nuclear
      pore complex and functions in nuclear mRNA export.
AB  - Metazoan NXF1-p15 heterodimers promote the nuclear export of bulk mRNA across
      nuclear pore complexes (NPCs). In vitro, NXF1-p15 forms a stable complex with the
      nucleoporin RanBP2/Nup358, a component of the cytoplasmic filaments of the NPC,
      suggesting a role for this nucleoporin in mRNA export. We show that depletion of
      RanBP2 from Drosophila cells inhibits proliferation and mRNA export.
      Concomitantly, the localization of NXF1 at the NPC is strongly reduced and a
      significant fraction of this normally nuclear protein is detected in the
      cytoplasm. Under the same conditions, the steady-state subcellular localization
      of other nuclear or cytoplasmic proteins and CRM1-mediated protein export are not
      detectably affected, indicating that the release of NXF1 into the cytoplasm and
      the inhibition of mRNA export are not due to a general defect in NPC function.
      The specific role of RanBP2 in the recruitment of NXF1 to the NPC is highlighted
      by the observation that depletion of CAN/Nup214 also inhibits cell proliferation
      and mRNA export but does not affect NXF1 localization. Our results indicate that
      RanBP2 provides a major binding site for NXF1 at the cytoplasmic filaments of the
      NPC, thereby restricting its diffusion in the cytoplasm after NPC translocation.
      In RanBP2-depleted cells, NXF1 diffuses freely through the cytoplasm.
      Consequently, the nuclear levels of the protein decrease and export of bulk mRNA
      is impaired.

PMID- 14729962
TI  - More than blood, a novel gene required for mammalian postimplantation
      development.
AB  - More than blood (Mtb) is a novel gene that is widely expressed in mouse embryos
      prior to gastrulation but is subsequently restricted to specific tissues,
      including the developing central nervous system and hematopoietic organs. Since
      MTB is highly expressed in the fetal liver and developing thymus, we predicted
      that MTB would be required for hematopoiesis and that embryos deficient in MTB
      would die of anemia. Surprisingly, embryos with a targeted disruption of Mtb died
      prior to the initiation of blood cell development, immediately following
      implantation. This lethality is due to a defect in expansion of the inner cell
      mass (ICM), as Mtb(-/-) blastocysts failed to exhibit outgrowth of the ICM, both
      in vitro and in vivo. Furthermore, Mtb(-/-) blastocysts exhibited a higher
      frequency of apoptotic cells than wild-type or heterozygous blastocysts. These
      findings demonstrate that Mtb is a novel gene that is essential for early
      embryonic development.

PMID- 14729963
TI  - Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing
      regulator in vivo.
AB  - Human RNPS1 was originally purified and characterized as a pre-mRNA splicing
      activator, and its role in the postsplicing process has also been proposed
      recently. To search for factors that functionally interact with RNPS1, we
      performed a yeast two-hybrid screen with a human cDNA library. Four factors were
      identified: p54 (also called SRp54; a member of the SR protein family), human
      transformer 2 beta (hTra2 beta; an exonic splicing enhancer-binding protein),
      hLucA (a potential component of U1 snRNP), and pinin (also called DRS and MemA; a
      protein localized in nuclear speckles). The N-terminal region containing the
      serine-rich (S) domain, the central RNA recognition motif (RRM), and the C
      terminal arginine/serine/proline-rich (RS/P) domain of RNPS1 interact with p54,
      pinin, and hTra2 beta, respectively. Protein-protein binding between RNPS1 and
      these factors was verified in vitro and in vivo. Overexpression of RNPS1 in HeLa
      cells induced exon skipping in a model beta-globin pre-mRNA and a human tra-2
      beta pre-mRNA. Coexpression of RNPS1 with p54 cooperatively stimulated exon
      inclusion in an ATP synthase gamma-subunit pre-mRNA. The RS/P domain and RRM are
      necessary for the exon-skipping activity, whereas the S domain is important for
      the cooperative effect with p54. RNPS1 appears to be a versatile factor that
      regulates alternative splicing of a variety of pre-mRNAs.

PMID- 14729964
TI  - BRG1 controls the activity of the retinoblastoma protein via regulation of
      p21CIP1/WAF1/SDI.
AB  - The ubiquitous mammalian chromatin-remodeling SWI/SNF-like BAF complexes play
      critical roles in tumorigenesis. It was suggested that the direct interaction of
      BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle
      progression by pRB. We present evidence that the BRG1-containing complexes
      regulate the expression of the cdk inhibitor p21(CIP1/WAF1/SDI). Furthermore, we
      show that the physical interaction between BRG1 and pRB is not required for
      induction of cell growth arrest and transcriptional repression of E2F target
      genes by pRB. Instead, BRG1 activates pRB by inducing its hypophosphorylation
      through up-regulation of the cdk inhibitor p21. The hypophosphorylation of pRB is
      reinforced by down-regulation of critical components, including cdk2, cyclin E,
      and cyclin D, in the pRB regulatory network. We demonstrate that up-regulation of
      p21 by BRG1 is necessary to induce formation of flat cells, growth arrest, and
      finally, cell senescence. Our results suggest that the BRG1-containing complexes
      control cellular proliferation and senescence by modulating the pRB pathway via
      multiple mechanisms.

PMID- 14729965
TI  - Growth retardation, early death, and DNA repair defects in mice deficient for the
      nucleotide excision repair enzyme XPF.
AB  - Xeroderma pigmentosum (XP) is a human genetic disease which is caused by defects
      in nucleotide excision repair. Since this repair pathway is responsible for
      removing UV irradiation-induced damage to DNA, XP patients are hypersensitive to
      sunlight and are prone to develop skin cancer. Based on the underlying genetic
      defect, the disease can be divided into the seven complementation groups XPA
      through XPG. XPF, in association with ERCC1, constitutes a structure-specific
      endonuclease that makes an incision 5' to the photodamage. XPF-ERCC1 has also
      been implicated in both removal of interstrand DNA cross-links and homology
      mediated recombination and in immunoglobulin class switch recombination (CSR). To
      study the function of XPF in vivo, we inactivated the XPF gene in mice. XPF
      deficient mice showed a severe postnatal growth defect and died approximately 3
      weeks after birth. Histological examination revealed that the liver of mutant
      animals contained abnormal cells with enlarged nuclei. Furthermore, embryonic
      fibroblasts defective in XPF are hypersensitive to UV irradiation and mitomycin C
      treatment. No defect in CSR was detected, suggesting that the nuclease is
      dispensable for this recombination process. These phenotypes are identical to
      those exhibited by the ERCC1-deficient mice, consistent with the functional
      association of the two proteins. The complex phenotype suggests that XPF-ERCC1 is
      involved in multiple DNA repair processes.

PMID- 14729966
TI  - ERF nuclear shuttling, a continuous monitor of Erk activity that links it to cell
      cycle progression.
AB  - The ets domain transcriptional repressor ERF is an effector of the receptor
      tyrosine kinase/Ras/Erk pathway, which, it has been suggested, is regulated by
      subcellular localization as a result of Erk-dependent phosphorylation and is
      capable of suppressing cell proliferation and ras-induced tumorigenicity. Here,
      we analyze the effect of ERF phosphorylation on nuclear import and export, the
      timing of its phosphorylation and dephosphorylation in relation to its
      subcellular location, Erk activity, and the requirements for ERF-induced cell
      cycle arrest. Our findings indicate that ERF continuously shuttles between the
      nucleus and the cytoplasm and that both phosphorylation and dephosphorylation of
      ERF occur within the nucleus. While nuclear import is not affected by
      phosphorylation, ERF nuclear export and cytoplasmic release require multisite
      phosphorylation and dephosphorylation. ERF export is CRM1 dependent, although ERF
      does not have a detectable nuclear export signal. ERF phosphorylation and export
      correlate with the levels of nuclear Erk activity. The cell cycle arrest induced
      by nonphosphorylated ERF requires the wild-type retinoblastoma protein and can be
      suppressed by overexpression of cyclin. These data suggest that ERF may be a very
      sensitive and constant sensor of Erk activity that can affect cell cycle
      progression through G(1), providing another link between the Ras/Erk pathway and
      cellular proliferation.

PMID- 14729968
TI  - The ctf13-30/CTF13 genomic haploinsufficiency modifier screen identifies the
      yeast chromatin remodeling complex RSC, which is required for the establishment
      of sister chromatid cohesion.
AB  - The budding yeast centromere-kinetochore complex ensures high-fidelity chromosome
      segregation in mitosis and meiosis by mediating the attachment and movement of
      chromosomes along spindle microtubules. To identify new genes and pathways whose
      function impinges on chromosome transmission, we developed a genomic
      haploinsufficiency modifier screen and used ctf13-30, encoding a mutant core
      kinetochore protein, as the reference point. We demonstrate through a series of
      secondary screens that the genomic modifier screen is a successful method for
      identifying genes that encode nonessential proteins required for the fidelity of
      chromosome segregation. One gene isolated in our screen was RSC2, a nonessential
      subunit of the RSC chromatin remodeling complex. rsc2 mutants have defects in
      both chromosome segregation and cohesion, but the localization of kinetochore
      proteins to centromeres is not affected. We determined that, in the absence of
      RSC2, cohesin could still associate with chromosomes but fails to achieve proper
      cohesion between sister chromatids, indicating that RSC has a role in the
      establishment of cohesion. In addition, numerous subunits of RSC were affinity
      purified and a new component of RSC, Rtt102, was identified. Our work indicates
      that only a subset of the nonessential RSC subunits function in maintaining
      chromosome transmission fidelity.

PMID- 14729967
TI  - Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and
      apoptotic pathways following DNA damage.
AB  - We have used genetic and microarray analysis to determine how ionizing radiation
      (IR) induces p53-dependent transcription and apoptosis in Drosophila
      melanogaster. IR induces MNK/Chk2-dependent phosphorylation of p53 without
      changing p53 protein levels, indicating that p53 activity can be regulated
      without an Mdm2-like activity. In a genome-wide analysis of IR-induced
      transcription in wild-type and mutant embryos, all IR-induced increases in
      transcript levels required both p53 and the Drosophila Chk2 homolog MNK.
      Proapoptotic targets of p53 include hid, reaper, sickle, and the tumor necrosis
      factor family member EIGER: Overexpression of Eiger is sufficient to induce
      apoptosis, but mutations in Eiger do not block IR-induced apoptosis. Animals
      heterozygous for deletions that span the reaper, sickle, and hid genes exhibited
      reduced IR-dependent apoptosis, indicating that this gene complex is
      haploinsufficient for induction of apoptosis. Among the genes in this region, hid
      plays a central, dosage-sensitive role in IR-induced apoptosis. p53 and MNK/Chk2
      also regulate DNA repair genes, including two components of the nonhomologous end
      joining repair pathway, Ku70 and Ku80. Our results indicate that MNK/Chk2
      dependent modification of Drosophila p53 activates a global transcriptional
      response to DNA damage that induces error-prone DNA repair as well as intrinsic
      and extrinsic apoptosis pathways.

PMID- 14729969
TI  - Role for the pleckstrin homology domain-containing protein CKIP-1 in
      phosphatidylinositol 3-kinase-regulated muscle differentiation.
AB  - In this work, we report the implication of the pleckstrin homology (PH) domain
      containing protein CKIP-1 in phosphatidylinositol 3-kinase (PI3-K)-regulated
      muscle differentiation. CKIP-1 is upregulated during muscle differentiation in
      C2C12 cells. We show that CKIP-1 binds to phosphatidylinositol 3-phosphate
      through its PH domain and localizes to the plasma membrane in a PI3-K-dependent
      manner. Activation of PI3-K by insulin or expression of an active form of PI3-K
      p110 induces a rapid translocation of CKIP-1 to the plasma membrane. Conversely,
      expression of the 3-phosphoinositide phosphatase myotubularin or PI3-K inhibition
      by LY294002, wortmannin, or mutant p85 abolishes CKIP-1 binding to the membrane.
      Upon induction of differentiation in low-serum medium, CKIP-1 overexpression in
      C2C12 myoblasts first promotes proliferation and then stimulates the expression
      of myogenin and cell fusion in a manner reminiscent of the dual positive effect
      of insulin-like growth factors on muscle cells. Interference with the PI3-K
      pathway impedes the effect of CKIP-1 on C2C12 cell differentiation. Finally,
      silencing of CKIP-1 by RNA interference abolishes proliferation and delays
      myogenin expression. Altogether, these data strongly implicate CKIP-1 as a new
      component of PI3-K signaling in muscle differentiation.

PMID- 14729970
TI  - E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro
      T cells that cause acute T-lymphoid or myeloid leukemias in mice.
AB  - Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of
      human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of
      primary myeloid progenitors but, paradoxically, induces apoptosis in established
      pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in
      cultured lymphoid progenitors. Here, we demonstrate that E2a/Pbx1 induces
      immortal proliferation of stem cell factor (SCF)-dependent pro-T thymocytes by a
      mechanism dependent upon both its transactivation and DNA-binding functions. E2a
      Pbx1 cooperated with cytokines or activated signaling oncoproteins to induce cell
      division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro
      T cells or pro-T cells made factor independent by expression of Bcr/Abl resulted
      in pro-T-cell quiescence, while reactivation of E2a/Pbx1 restored cell division.
      Infusion of E2a/Pbx1 pro-T cells in mice caused T lymphoblastic leukemia and,
      unexpectedly, acute myeloid leukemia. The acute lymphoblastic leukemia did not
      evidence further maturation, suggesting that E2a/Pbx1 establishes an early block
      in pro-T-cell development that cannot be overcome by marrow or thymic
      microenvironments. In an E2a/Pbx1 pro-T thymocyte clone that induced only pro-T
      acute lymphoblastic leukemia, coexpression of Bcr/Abl expanded its leukemic
      phenotype to include acute myeloid leukemia, suggesting that unique functions of
      cooperating signaling oncoproteins can influence the lymphoid versus myeloid
      character of E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate the pre
      B-cell phenotype of human leukemia containing t(1;19).

PMID- 14729971
TI  - Continuous zebularine treatment effectively sustains demethylation in human
      bladder cancer cells.
AB  - During tumorigenesis, tumor suppressor and cancer-related genes are commonly
      silenced by aberrant DNA methylation in their promoter regions. Recently, we
      reported that zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one]
      acts as an inhibitor of DNA methylation and exhibits chemical stability and
      minimal cytotoxicity both in vitro and in vivo. Here we show that continuous
      application of zebularine to T24 cells induces and maintains p16 gene expression
      and sustains demethylation of the 5' region for over 40 days, preventing
      remethylation. In addition, continuous zebularine treatment effectively and
      globally demethylated various hypermethylated regions, especially CpG-poor
      regions. The drug caused a complete depletion of extractable DNA
      methyltransferase 1 (DNMT1) and partial depletion of DNMT3a and DNMT3b3. Last,
      sequential treatment with 5-aza-2'-deoxycytidine followed by zebularine hindered
      the remethylation of the p16 5' region and gene resilencing, suggesting the
      possible combination use of both drugs as a potential anticancer regimen.

PMID- 14729972
TI  - Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S
      phase arrest.
AB  - Bloom's syndrome (BS) is a human genetic disorder associated with cancer
      predisposition. The BS gene product, BLM, is a member of the RecQ helicase
      family, which is required for the maintenance of genome stability in all
      organisms. In budding and fission yeasts, loss of RecQ helicase function confers
      sensitivity to inhibitors of DNA replication, such as hydroxyurea (HU), by
      failure to execute normal cell cycle progression following recovery from such an
      S-phase arrest. We have examined the role of the human BLM protein in recovery
      from S-phase arrest mediated by HU and have probed whether the stress-activated
      ATR kinase, which functions in checkpoint signaling during S-phase arrest, plays
      a role in the regulation of BLM function. We show that, consistent with a role
      for BLM in protection of human cells against the toxicity associated with arrest
      of DNA replication, BS cells are hypersensitive to HU. BLM physically associates
      with ATR (ataxia telangiectasia and rad3(+) related) protein and is
      phosphorylated on two residues in the N-terminal domain, Thr-99 and Thr-122, by
      this kinase. Moreover, BS cells ectopically expressing a BLM protein containing
      phosphorylation-resistant T99A/T122A substitutions fail to adequately recover
      from an HU-induced replication blockade, and the cells subsequently arrest at a
      caffeine-sensitive G(2)/M checkpoint. These abnormalities are not associated with
      a failure of the BLM-T99A/T122A protein to localize to replication foci or to
      colocalize either with ATR itself or with other proteins that are required for
      response to DNA damage, such as phosphorylated histone H2AX and RAD51. Our data
      indicate that RecQ helicases play a conserved role in recovery from perturbations
      in DNA replication and are consistent with a model in which RecQ helicases act to
      restore productive DNA replication following S-phase arrest and hence prevent
      subsequent genomic instability.

PMID- 14729973
TI  - Quaternary structure of ATR and effects of ATRIP and replication protein A on its
      DNA binding and kinase activities.
AB  - ATR is an essential protein that functions as a damage sensor and a proximal
      kinase in the DNA damage checkpoint response in mammalian cells. It is a member
      of the phosphoinositide 3-kinase-like kinase (PIKK) family, which includes ATM,
      ATR, and DNA-dependent protein kinase. Recently, it was found that ATM is an
      oligomeric protein that is converted to an active monomeric form by
      phosphorylation in trans upon DNA damage, and this raised the possibility that
      other members of the PIKK family may be regulated in a similar manner. Here we
      show that ATR is a monomeric protein associated with a smaller protein called
      ATRIP with moderate affinity. The ATR protein by itself or in the form of the ATR
      ATRIP heterodimer binds to naked or replication protein A (RPA)-covered DNAs with
      comparable affinities. However, the phosphorylation of RPA by ATR is dependent on
      single-stranded DNA and is stimulated by ATRIP. These findings suggest that the
      regulation and mechanism of action of ATR are fundamentally different from those
      of the other PIKK proteins.

PMID- 14729974
TI  - Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and
      longevity.
AB  - The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone
      deacetylase (HDAC) that functions in transcriptional silencing and longevity. The
      NAD(+) salvage pathway protein, Npt1, regulates Sir2-mediated processes by
      maintaining a sufficiently high intracellular NAD(+) concentration. However,
      another NAD(+) salvage pathway component, Pnc1, modulates silencing independently
      of the NAD(+) concentration. Nicotinamide (NAM) is a by-product of the Sir2
      deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase
      that converts NAM to nicotinic acid. Here we show that recombinant Pnc1
      stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM
      produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially
      sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the
      inhibitory effect of exogenously added NAM on silencing, life span, and Hst1
      mediated transcriptional repression. Finally, we show that stress suppresses the
      inhibitory effect of NAM through the induction of PNC1 expression. Pnc1,
      therefore, positively regulates Sir2-mediated silencing and longevity by
      preventing the accumulation of intracellular NAM during times of stress.

PMID- 14729975
TI  - Tissue-selective, bidirectional regulation of PEX11 alpha and perilipin genes
      through a common peroxisome proliferator response element.
AB  - Most cis-acting regulatory elements have generally been assumed to activate a
      single nearby gene. However, many genes are clustered together, raising the
      possibility that they are regulated through a common element. We show here that a
      single peroxisome proliferator response element (PPRE), located between the mouse
      PEX11 alpha and perilipin genes, confers on both genes activation by peroxisome
      proliferator-activated receptor alpha (PPAR alpha) and PPAR gamma. A functional
      PPRE 8.4 kb downstream of the promoter of PEX11 alpha, a PPAR alpha target gene,
      was identified by a gene transfection study. This PPRE was positioned 1.9 kb
      upstream of the perilipin gene and also functioned with the perilipin promoter.
      In addition, this PPRE, when combined with the natural promoters of the PEX11
      alpha and perilipin genes, conferred subtype-selective activation by PPAR alpha
      and PPAR gamma 2. The PPRE sequence specifically bound to the heterodimer of RXR
      alpha and PPAR alpha or PPAR gamma 2, as assessed by electrophoretic gel mobility
      shift assays. Furthermore, tissue-selective binding of PPAR alpha and PPAR gamma
      to the PPRE was demonstrated in hepatocytes and adipocytes, respectively, by
      chromatin immunoprecipitation assay. Hence, the expression of these genes is
      induced through the same PPRE in the liver and adipose tissue, where the two PPAR
      subtypes are specifically expressed.

PMID- 14729976
TI  - Preferential transcription of rabbit Aldh1a1 in the cornea: implication of
      hypoxia-related pathways.
AB  - Here we examine the molecular basis for the known preferential expression of
      rabbit aldehyde dehydrogenase class 1 (ALDH1A1) in the cornea. The rabbit Aldh1a1
      promoter-firefly luciferase reporter transgene (-3519 to +43) was expressed
      preferentially in corneal cells in transfection tests and in transgenic mice,
      with an expression pattern resembling that of rabbit Aldh1a1. The 5' flanking
      region of the rabbit Aldh1a1 gene resembled that in the human gene (60.2%) more
      closely than that in the mouse (46%) or rat (51.5%) genes. We detected three
      xenobiotic response elements (XREs) and one E-box consensus sequence in the
      rabbit Aldh1a1 upstream region; these elements are prevalent in other highly
      expressed corneal genes and can mediate stimulation by dioxin and repression by
      CoCl(2), which simulates hypoxia. The rabbit Aldh1a1 promoter was stimulated
      fourfold by dioxin in human hepatoma cells and repressed threefold by CoCl(2)
      treatment in rabbit corneal stromal and epithelial cells. Cotransfection,
      mutagenesis, and gel retardation experiments implicated the hypoxia-inducible
      factor 3alpha/aryl hydrocarbon nuclear translocator heterodimer for Aldh1a1
      promoter activation via the XREs and stimulated by retinoic acid protein 13 for
      promoter repression via the E-box. These experiments suggest that XREs, E-boxes,
      and PAS domain/basic helix-loop-helix transcription factors (bHLH-PAS) contribute
      to preferential rabbit Aldh1a1 promoter activity in the cornea, implicating
      hypoxia-related pathways.

PMID- 14729977
TI  - ASPP1 and ASPP2: common activators of p53 family members.
AB  - We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53.
      We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By
      binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the
      transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA
      but not mdm2 or p21(WAF-1/CIP1). The expression of ASPP1 and ASPP2 also enhances
      the apoptotic function of p63 and p73 by selectively inducing the expression of
      endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21(WAF
      1/CIP1). Removal of endogenous p63 or p73 with RNA interference demonstrated that
      (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly
      by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common
      activators of all p53 family members. All these results suggest that ASPP1 and
      ASPP2 could suppress tumor growth even in tumors expressing mutant p53.

PMID- 14729978
TI  - Microhomology-dependent end joining and repair of transposon-induced DNA hairpins
      by host factors in Saccharomyces cerevisiae.
AB  - The maize, cut-and-paste transposon Ac/Ds is mobile in Saccharomyces cerevisiae,
      and DNA sequences of repair products provide strong genetic evidence that hairpin
      intermediates form in host DNA during this transposition, similar to those formed
      for V(D)J coding joints in vertebrates. Both DNA strands must be broken for Ac/Ds
      to excise, suggesting that double-strand break (DSB) repair pathways should be
      involved in repair of excision sites. In the absence of homologous template, as
      expected, Ac excisions are repaired by nonhomologous end joining (NHEJ) that can
      involve microhomologies close to the broken ends. However, unlike repair of
      endonuclease-induced DSBs, repair of Ac excisions in the presence of homologous
      template occurs by gene conversion only about half the time, the remainder being
      NHEJ events. Analysis of transposition in mutant yeast suggests roles for the
      Mre11/Rad50 complex, SAE2, NEJ1, and the Ku complex in repair of excision sites.
      Separation-of-function alleles of MRE11 suggest that its endonuclease function is
      more important in this repair than either its exonuclease or Rad50-binding
      properties. In addition, the interstrand cross-link repair gene PSO2 plays a role
      in end joining hairpin ends that is not seen in repair of linearized plasmids and
      may be involved in positioning transposase cleavage at the transposon ends.

PMID- 14729979
TI  - Activating transcription factor 3 is integral to the eukaryotic initiation factor
      2 kinase stress response.
AB  - In response to environmental stress, cells induce a program of gene expression
      designed to remedy cellular damage or, alternatively, induce apoptosis. In this
      report, we explore the role of a family of protein kinases that phosphorylate
      eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We
      find that expression of activating transcription factor 3 (ATF3), a member of the
      ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in
      response to endoplasmic reticulum (ER) stress or amino acid starvation by a
      mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4),
      respectively. Increased expression of ATF3 protein occurs early in response to
      stress by a mechanism requiring the related bZIP transcriptional regulator ATF4.
      ATF3 contributes to induction of the CHOP transcriptional factor in response to
      amino acid starvation, and loss of ATF3 function significantly lowers stress
      induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit
      implicated in feedback control of the eIF2 kinase stress response. Overexpression
      of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK
      for induction of GADD34 in response to ER stress, further supporting the idea
      that ATF3 functions directly or indirectly as a transcriptional activator of
      genes targeted by the eIF2 kinase stress pathway. These results indicate that
      ATF3 has an integral role in the coordinate gene expression induced by eIF2
      kinases. Given that ATF3 is induced by a very large number of environmental
      insults, this study supports involvement of eIF2 kinases in the coordination of
      gene expression in response to a more diverse set of stress conditions than
      previously proposed.

PMID- 14729980
TI  - Receptor clustering is involved in Reelin signaling.
AB  - The Reelin signaling cascade plays a crucial role in the correct positioning of
      neurons during embryonic brain development. Reelin binding to apolipoprotein E
      receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to
      phosphorylation of disabled 1 (Dab1), an adaptor protein which associates with
      the intracellular domains of both receptors. Coreceptors for Reelin have been
      postulated to be necessary for Dab1 phosphorylation. We show that bivalent agents
      specifically binding to ApoER2 or VLDLR are sufficient to mimic the Reelin
      signal. These agents induce Dab1 phosphorylation, activate members of the Src
      family of nonreceptor tyrosine kinases, modulate protein kinase B/Akt
      phosphorylation, and increase long-term potentiation in hippocampal slices.
      Induced dimerization of Dab1 in HEK293 cells leads to its phosphorylation even in
      the absence of Reelin receptors. The mechanism for and the sites of these
      phosphorylations are identical to those effected by Reelin in primary neurons.
      These results suggest that binding of Reelin, which exists as a homodimer in
      vivo, to ApoER2 and VLDLR induces clustering of ApoER2 and VLDLR. As a
      consequence, Dab1 becomes dimerized or oligomerized on the cytosolic side of the
      plasma membrane, constituting the active substrate for the kinase; this process
      seems to be sufficient to transmit the signal and does not appear to require any
      coreceptor.

PMID- 14729981
TI  - RNA folding affects the recruitment of SR proteins by mouse and human polypurinic
      enhancer elements in the fibronectin EDA exon.
AB  - In humans, inclusion or exclusion of the fibronectin EDA exon is mainly regulated
      by a polypurinic enhancer element (exonic splicing enhancer [ESE]) and a nearby
      silencer element (exonic splicing silencer [ESS]). While human and mouse ESEs
      behave identically, mutations introduced into the homologous mouse ESS sequence
      result either in no change in splicing efficiency or in complete exclusion of the
      exon. Here, we show that this apparently contradictory behavior cannot be simply
      accounted for by a localized sequence variation between the two species. Rather,
      the nucleotide differences as a whole determine several changes in the respective
      RNA secondary structures. By comparing how the two different structures respond
      to homologous deletions in their putative ESS sequences, we show that changes in
      splicing behavior can be accounted for by a differential ESE display in the two
      RNAs. This is confirmed by RNA-protein interaction analysis of levels of SR
      protein binding to each exon. The immunoprecipitation patterns show the presence
      of complex multi-SR protein-RNA interactions that are lost with secondary
      structure variations after the introduction of ESE and ESS variations. Taken
      together, our results demonstrate that the sequence context, in addition to the
      primary sequence identity, can heavily contribute to the making of functional
      units capable of influencing pre-mRNA splicing.

PMID- 14729982
TI  - c-Kit-mediated overlapping and unique functional and biochemical outcomes via
      diverse signaling pathways.
AB  - A critical issue in understanding receptor tyrosine kinase signaling is the
      individual contribution of diverse signaling pathways in regulating cellular
      growth, survival, and migration. We generated a functionally and biochemically
      inert c-Kit receptor that lacked the binding sites for seven early signaling
      pathways. Restoring the Src family kinase (SFK) binding sites in the mutated c
      Kit receptor restored cellular survival and migration but only partially rescued
      proliferation and was associated with the rescue of the Ras/mitogen-activated
      protein kinase, Rac/JNK kinase, and phosphatidylinositol 3-kinase (PI-3
      kinase)/Akt pathways. In contrast, restoring the PI-3 kinase binding site in the
      mutated receptor did not affect cellular proliferation but resulted in a modest
      correction in cell survival and migration, despite a complete rescue in the
      activation of the PI-3 kinase/Akt pathway. Surprisingly, restoring the binding
      sites for Grb2, Grb7, or phospholipase C-gamma had no effect on cellular growth
      or survival, migration, or activation of any of the downstream signaling
      pathways. These results argue that SFKs play a unique role in the control of
      multiple cellular functions and in the activation of distinct biochemical
      pathways via c-Kit.

PMID- 14729984
TI  - Involvement of Rho family GTPases in p19Arf- and p53-mediated proliferation of
      primary mouse embryonic fibroblasts.
AB  - The Rho family GTPases Rac1, RhoA, and Cdc42 function as molecular switches that
      transduce intracellular signals regulating gene expression and cell proliferation
      as well as cell migration. p19(Arf) and p53, on the other hand, are tumor
      suppressors that act both independently and sequentially to regulate cell
      proliferation. To investigate the functional interaction and cooperativeness of
      Rho GTPases with the p19(Arf)-p53 pathway, we examined the contribution of Rho
      GTPases to the gene transcription and cell proliferation unleashed by deletion of
      p19Arf or p53 in primary mouse embryo fibroblasts. We found that (i) p19(Arf) or
      p53 deficiency led to a significant increase in PI 3-kinase activity, which in
      turn upregulated RhoA and Rac1 activities; (ii) deletion of p19Arf or p53 led to
      an increase in cell growth rate that was in part dependent on RhoA, Rac1, and
      Cdc42 activities; (iii) p19(Arf) or p53 deficiency caused an enhancement of the
      growth-related transcription factor NF-kappa B and cyclin D1 activities that are
      partly dependent on RhoA or Cdc42 but not on Rac1; (iv) forced expression of the
      activating mutants of Rac1, RhoA, or Cdc42 caused a hyperproliferative phenotype
      of the p19Arf(-/-) and p53(-/-) cells and promoted transformation of both cells;
      (v) RhoA appeared to contribute to p53-regulated cell proliferation by modulating
      cell cycle machinery, while hyperactivation of RhoA further suppressed a p53
      independent apoptotic signal; and (vi) multiple pathways regulated by RhoA,
      including that of Rho-kinase, were required for RhoA to fully promote the
      transformation of p53(-/-) cells. Taken together, these results provide strong
      evidence indicating that signals through the Rho family GTPases can both
      contribute to cell growth regulation by p19Arf and p53 and cooperate with p19Arf
      or p53 deficiency to promote primary cell transformation.

PMID- 14729985
TI  - Changes in plantar foot pressure with in-shoe varus or valgus wedging.
AB  - Varus and valgus wedging are commonly used by podiatric physicians in therapy
      with custom-made foot orthoses. This study aimed to provide scientific evidence
      of the effects on plantar foot pressure of applying in-shoe forefoot or rearfoot
      wedging. The plantar foot pressure distribution of 23 subjects walking on a
      treadmill was recorded using a pressure insole system for seven different wedging
      conditions, ranging from 3 degrees valgus to 6 degrees varus for the forefoot and
      from 4 degrees valgus to 8 degrees varus for the rearfoot. The results
      demonstrate that increasing varus wedging magnifies peak pressure and maximal
      loading rate at the medial forefoot and rearfoot, whereas increasing valgus
      wedging magnifies peak pressure and maximal loading rate at the lateral forefoot
      and rearfoot. As expected, the location of the center of pressure shifts medially
      with varus wedging and laterally with valgus wedging. However, these shifts are
      less significant than those in peak load and maximal loading rate. Timing
      variables such as interval from initial impact to peak load do not seem to be
      affected by forefoot or rearfoot wedging. Finally, rearfoot wedging does not
      significantly influence pressure variables of the forefoot; similarly, rearfoot
      pressure remains unaffected by forefoot wedging.

PMID- 14729983
TI  - Transforming growth factor beta/Smad3 signaling regulates IRF-7 function and
      transcriptional activation of the beta interferon promoter.
AB  - The rapid induction of alpha interferon (IFN-alpha) and IFN-beta expression plays
      a critical role in the innate immune response against viral infection. We studied
      the effects of transforming growth factor beta (TGF-beta) and its intracellular
      effectors, the Smads, on the function of IRF-7, an essential transcription factor
      for IFN-alpha and -beta induction. IRF-7 interacted with Smads, and IRF-7, but
      not IRF-3, cooperated with Smad3 to activate IFN-beta transcription. This
      transcriptional cooperation occurred at the IRF-binding sequences in the IFN-beta
      promoter, and dominant-negative interference with TGF-beta receptor signaling and
      Smad3 function decreased IRF-7-mediated transcription. Furthermore, elimination
      of Smad3 expression in Smad3(-/-) fibroblasts delayed and decreased double
      stranded RNA-induced expression of endogenous IFN-beta, whereas restoration of
      Smad3 expression enhanced IFN-beta induction. The IRF-7-Smad3 cooperativity
      resulted from the regulation of the transactivation activity of IRF-7 by Smad3,
      and dominant-negative interference with Smad3 function decreased IRF-7 activity.
      Consistent with the regulation by Smad3, the transcriptional activity of IRF-7
      depended on and was regulated by TGF-beta signaling. Our studies underscore a
      role of TGF-beta/Smad3 signaling in IRF-7-mediated induction of IFN-beta
      expression.

PMID- 14729986
TI  - Triple arthrodesis using external ring fixation and arched-wire compression: an
      evaluation of 87 patients.
AB  - From January 1995 to December 2000, 87 patients at a single medical center
      underwent triple arthrodesis using external rings and arched-wire compression as
      the method of fixation. A retrospective evaluation was conducted to assess the
      clinical results of this technique. Eighty-four patients (97%) achieved clinical
      and radiographic fusion in 6 to 8 weeks. All of the patients were partially
      weightbearing during the first postoperative week. Thirty-one patients (36%)
      developed a superficial infection at one or more wire insertion sites, and nine
      (10%) experienced dehiscence of an incision. Three patients (3%) developed an
      asymptomatic nonunion. This article describes the use of external ring fixation
      with arched-wire compression for triple arthrodesis and presents the findings
      from 87 patients who underwent this technique.

PMID- 14729987
TI  - Plantar pressure and joint motion after the Youngswick procedure for hallux
      limitus.
AB  - The effects of the Youngswick osteotomy on plantar peak pressure distribution in
      the forefoot are presented for 17 patients (23 feet) with mild-to-moderate hallux
      limitus deformity and 23 control subjects (23 feet). During 2 years of follow-up,
      the operation produced a significant increase in the range of dorsiflexion of the
      first metatarsophalangeal joint in these patients, reaching near-normal values.
      Preoperative and postoperative measurements, using a pressure-distribution
      measurement system, show that peak pressure beneath the hallux and the first
      metatarsal head remained unchanged. However, peak pressure was significantly
      increased beneath the second metatarsal head and decreased beneath the fifth
      metatarsal head. These findings suggest that the foot functioned in a less
      inverted manner postoperatively. Compared with normal feet, hallux limitus feet
      demonstrated significantly higher peak pressure beneath the fourth metatarsal
      head preoperatively and postoperatively.

PMID- 14729988
TI  - Criterion validation of four criteria of the foot posture index.
AB  - The Foot Posture Index is a new multidimensional and multiplanar tool aimed at
      quantifying the degree of pronation to supination of the foot, comprising eight
      criteria that sum to produce a final "score" of foot posture. In an initial study
      involving 31 subjects, angulations measured from dorsoplantar and lateral
      radiographs were compared with the corresponding Foot Posture Index criteria
      using Spearman's rho and the generalized linear model of analysis of variance.
      Eleven of the participants from Study 1 completed a second study in which wedges
      were used to alter foot position to determine whether changes to foot position
      were sensitively reflected in Foot Posture Index criterion scores and associated
      radiographic images. Study 1 demonstrated a significant correlation for only one
      criterion (talar head palpation), while Study 2 demonstrated intrasubject
      sensitivity to overall changes from supinated to pronated and supinated to
      resting positions but insensitivity to changes from resting to pronated
      positions. The results suggest that although the Foot Posture Index could be a
      useful tool to broadly classify foot postures, it is not sensitive to all small
      movements when assessed by this method.

PMID- 14729989
TI  - Plantar soft-tissue thickness predicts high peak plantar pressure in the diabetic
      foot.
AB  - The aim of this study was to evaluate whether high plantar foot pressures can be
      predicted from measurements of plantar soft-tissue thickness in the forefoot of
      diabetic patients with neuropathy. A total of 157 diabetic patients with
      neuropathy and at least one palpable foot pulse but without a history of foot
      ulceration were invited to participate in the study. Plantar tissue thickness was
      measured bilaterally at each metatarsal head, with patients standing on the same
      standardized platform. Plantar pressures were measured during barefoot walking
      using the optical pedobarograph. Receiver operating characteristic analysis was
      used to determine the plantar tissue thickness predictive of elevated peak
      plantar pressure. Tissue thickness cutoff values of 11.05, 7.85, 6.65, 6.55, and
      5.05 mm for metatarsal heads 1 through 5, respectively, predict plantar pressure
      at each respective site greater than 700 kPa, with sensitivity between 73% and
      97% and specificity between 52% and 84%. When tissue thickness was used to
      predict pressure greater than 1,000 kPa, similar results were observed,
      indicating that high pressure at different levels could be predicted from similar
      tissue thickness cutoff values. The results of the study indicate that high
      plantar pressure can be predicted from plantar tissue thickness with high
      sensitivity and specificity.

PMID- 14729990
TI  - Proximal oblique crescentic osteotomy in hallux valgus.
AB  - Twenty-six patients with moderate-to-severe hallux valgus deformities were
      evaluated before and after treatment. All of the patients had incongruent great
      toe joints. The patients underwent modified proximal crescentic osteotomy, which
      was termed proximal oblique crescentic osteotomy. The results were evaluated at
      an average follow-up time of 55 weeks. Objective criteria were hallux valgus
      angle, intermetatarsal angle, shortening of the first metatarsal, and angulation
      at the osteotomy site. Clinical evaluation was made according to the rating
      system of the American Orthopaedic Foot and Ankle Society. The mean correction of
      the hallux valgus and intermetatarsal angles was 22.1 degrees and 9.9 degrees,
      respectively. Short-term results indicate that proximal oblique crescentic
      osteotomy is effective in the treatment of hallux valgus; its advantages over
      other procedures include its technical ease and low rate of complications.

PMID- 14729991
TI  - Effects of changes in heel fat pad thickness and elasticity on heel pain.
AB  - The heel fat pad has a unique structure that is important for its shock-absorbing
      function. Loss of elasticity and changes in the thickness of the heel pad have
      been suggested as causes of heel pain. The present study of a population with
      heel pain shows the relationship between the thickness and elasticity of the heel
      fat pad and age, sex, obesity, duration of symptoms, subcalcaneal spurs, and
      noninvasive conservative treatment. Of 182 patients with heel pain who visited an
      outpatient clinic during a 3-year period, 50 (67 heels) fulfilling specific
      criteria were treated with a combination of nonsteroidal anti-inflammatory drugs,
      contrast baths, stretching exercises, and change of footwear habits. Patients
      were followed up for 1 year. Delayed healing, increased thickness, and decreased
      elasticity of the heel fat pad were found in patients who were older than 40
      years, who had symptoms for longer than 12 months before treatment, and who had a
      large subcalcaneal spur. An increase in heel fat pad thickness with aging and
      increased body weight reduce the elasticity of the heel fat pad. In addition,
      subcalcaneal spurs diminish the elasticity of the heel fat pad and play a role in
      the formation of heel pain.

PMID- 14729992
TI  - Does footwear affect ankle coordination strategies?
AB  - The hypothesis of this study was that shoe hardness and footwear affect ankle
      coordinative strategies during the running stance period. Subjects ran at a self
      selected pace under three conditions-barefoot, wearing a hard shoe, and wearing a
      soft shoe-while sagittal and frontal view kinematic data were collected. Dynamic
      systems theory tools were used to explore ankle coordinative strategies under the
      three conditions. No significant differences in coordination were found between
      the two shoe conditions. However, significant differences in ankle coordinative
      strategies existed between the shoe conditions and the barefoot condition.
      Changes in coordinative strategies may be related to different mechanisms to
      attenuate impact forces while running barefoot.

PMID- 14729993
TI  - Neurothekeoma in the foot: a rare occurrence.
AB  - Neurothekeoma is a benign cutaneous neoplasm of nerve sheath origin. This seldom
      seen entity is especially rare in the foot. We provide an overview of
      neurothekeoma and describe a patient with an occurrence in the foot that was
      effectively treated by complete excision of the mass.

PMID- 14729994
TI  - Carbon dioxide laser and Apligraf for a painful plantar hypertrophic scar.
AB  - We report on a patient with a large, painful hypertrophic scar on the plantar
      aspect of the left foot who was treated with carbon dioxide laser and a skin
      substitute (Apligraf) and followed up for longer than 1 year. To our knowledge,
      no other case reports have been published on the use of a skin substitute to gain
      coverage and resolution after excision of a hypertrophic scar by carbon dioxide
      laser.

PMID- 14729995
TI  - Lateral subtalar joint dislocation: a case with calcaneal fracture.
AB  - Subtalar joint dislocation is a relatively rare injury, with lateral dislocation
      occurring less frequently than medial dislocation. Associated fractures alter the
      treatment plan and the prognosis, but they are often missed on plain film
      radiographs. A brief review of the anatomy, pathomechanics, treatment, prognosis,
      and complications of subtalar joint dislocation is presented. An interesting case
      of lateral subtalar joint dislocation with an associated calcaneal fracture not
      evident on plain film radiographs but delineated with computed tomography is
      presented.

PMID- 14729996
TI  - Hallux proximal phalanx Akin-Scarf osteotomy.
AB  - Numerous hallux proximal phalanx osteotomies have been described, but the Akin
      type varisation or adduction osteotomies are currently the most commonly used by
      foot and ankle surgeons. This article describes the hallux proximal phalanx Akin
      Scarf osteotomy. This osteotomy combines the inherent stability of the Scarf-type
      osteotomy with the versatility of the Akin-type osteotomies to correct pathologic
      hallux abductus interphalangeus, hallux equinus, or an abnormal digital length
      pattern, and it is an invaluable tool during the global surgical approach used
      for hallux valgus repair.

PMID- 14729997
TI  - Onychauxic dystrophic toenails requiring debridement in Medicare patients.

PMID- 14729998
TI  - Onychauxic dystrophic toenails requiring debridement in Medicare patients.

PMID- 14729999
TI  - Onychauxic dystrophic toenails requiring debridement in Medicare patients.

PMID- 14730001
TI  - Onychauxic dystrophic toenails requiring debridement in Medicare patients.

PMID- 14730004
TI  - Brain stimulation for neurological and psychiatric disorders, current status and
      future direction.
AB  - Interest in brain stimulation therapies has been rejuvenated over the last decade
      and brain stimulation therapy has become an alternative treatment for many
      neurological and psychiatric disorders, including Parkinson's disease (PD),
      dystonia, pain, epilepsy, depression, and schizophrenia. The effects of brain
      stimulation on PD are well described, and this treatment has been widely used for
      such conditions worldwide. Treatments for other conditions are still in
      experimental stages and large-scale, well controlled studies are needed to refine
      the treatment procedures. In the treatment of intractable brain disorders, brain
      stimulation, especially transcranial magnetic stimulation (TMS), is an attractive
      alternative to surgical lesioning as it is relatively safe, reversible, and
      flexible. Brain stimulation, delivered either via deeply implanted electrodes or
      from a surface-mounted transcranial magnetic device, can alter abnormal neural
      circuits underlying brain disorders. The neural mechanisms mediating the
      beneficial effects of brain stimulation, however, are poorly understood.
      Conflicting theories and experimental data have been presented. It seems that the
      action of stimulation on brain circuitry is not limited to simple excitation or
      inhibition. Alterations of neural firing patterns and long-term effects on
      neurotransmitter and receptor systems may also play important roles in the
      therapeutic effects of brain stimulation. Future research on both the basic and
      clinical fronts will deepen our understanding of how brain stimulation works.
      Real-time computation of neural activity allows for integration of brain
      stimulation signals into ongoing neural processing. In this way abnormal circuit
      activity can be adjusted by optimal therapeutic brain stimulation paradigms.

PMID- 14730006
TI  - An antiarrhythmic effect of a chymase inhibitor after myocardial infarction.
AB  - Chymase plays an important role in the regulation of local angiotensin (Ang) II
      formation in the cardiac tissue. We recently found that cardiac chymase was
      activated significantly and survival rate markedly improved by treatment with
      chymase inhibitors after myocardial infarction (MI) in hamsters. However, the
      mechanisms for this effect have not been established. Because lethal arrhythmias
      are generally believed to contribute to sudden cardiac death, we assessed whether
      inhibition of cardiac chymase would provide an antiarrhythmic effect during the 8
      h ischemic period after 2-[4-(5-fluoro-3-methylbenzo-[b]thiophen-2-yl)sulfonamide
      3-methanesulfonylphenyl]oxazole-4-carboxylicacid (TY51184) (a specific chymase
      inhibitor, 1 mg/kg i.v.) treatment by ligation of left anterior descending
      coronary artery (LAD) in dogs. Effects of candesartan (an Ang II type 1 receptor
      antagonist, 1 mg/kg i.v.) in this model were also assessed. Total Ang II-forming
      activity and chymase activity in the infarcted heart were increased significantly
      8 h after LAD ligation. A time-dependent elevation of Ang II in plasma was also
      observed. A decrease in plasma Ang II levels after TY51184 treatment occurred
      concomitantly with suppression of cardiac chymase activity. LAD ligation resulted
      in a large number of ventricular arrhythmias (VAs). TY51184 and candesartan
      treatments largely suppressed the appearance of VAs, and the efficacy of the two
      agents was similar. These findings demonstrate that chymase inhibition can
      provide an antiarrhythmic effect after MI, and the reduction of Ang II by TY51184
      may be mainly responsible for this beneficial effect. An antiarrhythmic effect of
      chymase inhibitors may contribute to reductions in the mortality rate during the
      acute phase after MI.

PMID- 14730005
TI  - In vivo activity of a phospholipase C inhibitor, 1-(6-((17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), in acute and
      chronic inflammatory reactions.
AB  - To investigate the role of phospholipase C (PLC) in inflammatory processes, we
      tested 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole
      2,5-dione (U73122), a widely used PLC inhibitor, in several in vitro and in vivo
      assays. We first examined the effects of U73122 on human phospholipase C-beta
      (PLC-beta) isozymes and found that U73122 significantly inhibited recombinant
      human PLC-beta2, with an IC(50) of approximately 6 microM. U73122 had little
      effect on PLC-beta1, PLC-beta3, or PLC-beta4. Consistent with its ability to
      inhibit PLC-beta2 enzymatic activity, U73122 reduced interleukin-8 and
      leukotriene B(4)-induced Ca(2+) flux and chemotaxis in human neutrophils in a
      concentration-dependent manner. In vivo, U73122 blocked carrageenan-induced hind
      paw edema in rats, carrageenan-induced macrophage and lymphocyte accumulation
      into subcutaneous chambers in dogs, lipopolysaccharide-induced macrophage,
      lymphocyte infiltration and prostaglandin E(2) production in a mouse peritonitis
      model, and 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice. These
      results implicate PLC-dependent signaling pathways in the development of acute
      and chronic inflammatory responses in vivo.

PMID- 14730007
TI  - DNA repair.

PMID- 14730008
TI  - Anna Starzinski-Powitz. Interview by Fiona Watt.

PMID- 14730009
TI  - Model organisms lead the way to protein palmitoyltransferases.
AB  - The acylation of proteins with palmitate and related fatty acids has been known
      for over 30 years, but the molecular machinery that carries out palmitoylation
      has only recently emerged from studies in the model organisms Saccharomyces
      cerevisiae and Drosophila. Two classes of protein acyltransferases (PATs) have
      been proposed. In yeast, members of a family of integral membrane proteins
      harboring a cysteine-rich domain (CRD) containing a conserved DHHC (Asp-His-His
      Cys) motif are PATs for cytoplasmic signaling molecules. The DHHC-CRD protein
      Erf2p, together with an associated subunit Erf4p, palmitoylates yeast Ras
      proteins, and Akr1p catalyzes the palmitoylation of the yeast casein kinase
      Yck2p. The existence of a second class of PATs that modify secreted signaling
      proteins has been suggested from work in Drosophila. Rasp is required in vivo for
      the production of functional Hedgehog and shares sequence identity with membrane
      bound O-acyltransferases, which suggests that it catalyzes the palmitoylation of
      Hedgehog. With the identification of PATs in model genetic organisms, the field
      is now poised to uncover their mammalian counterparts and to understand the
      enzymology of protein palmitoylation.

PMID- 14730010
TI  - Planar polarity from flies to vertebrates.
AB  - Planar cell polarity (PCP) has been demonstrated in the epithelium of organisms
      from flies to humans. Recent research has revealed that the planar organization
      of cells requires a conserved set of genes, known as the PCP genes. Tbe PCP
      proteins Frizzled (Fz) and Dishevelled (Dsh) function as key players in PCP
      signalling. Although Fz and Dsh are also involved in Wingless (Wg)/Wnt
      signalling, these proteins have independent functions in a non-canonical pathway
      dedicated to PCP. Reorganization of the cell surface and cytoskeleton is
      required, and recent work has focused on how cell adhesion molecules (such as
      Fat, Dachsous and Flamingo) function in this process.

PMID- 14730011
TI  - Missense mutations in the globular tail of myosin-Va in dilute mice partially
      impair binding of Slac2-a/melanophilin.
AB  - The well-known coat-color mutant mouse dilute exhibits a defect in melanosome
      transport, and although various mutations in the myosin-Va gene, which encodes an
      actin-based motor protein, have been identified in dilute mice, why missense
      mutations in the globular tail of myosin-Va, a putative cargo-binding site, cause
      the dilute phenotype (i.e. lighter coat color) has never been elucidated. In this
      study we discovered that missense mutations (I1510N, M1513K and D1519G) in the
      globular tail (GT) of myosin-Va partially impair the binding of Slac2
      a/melanophilin, a linker protein between myosin-Va and Rab27A on the melanosome.
      The myosin-Va-GT-binding site in Slac2-a was mapped to the region (amino acids
      147-240) adjacent to the N-terminal Rab27A-binding site, but it is distinct from
      the myosin-Va-exon-F-binding site (amino acids 320-406). The myosin-Va-GT.Slac2-a
      interaction was much weaker than the myosin-Va-exon-F.Slac2-a interaction. The
      missense mutations in the GT found in dilute mice abrogated only the myosin-Va
      GT.Slac2-a interaction and had no effect on the myosin-Va-exon-F.Slac2-a
      interaction. We further showed that expression of green fluorescence protein
      tagged Slac2-a lacking the myosin-Va-GT-binding site (DeltaGT), but not the wild
      type Slac2-a, severely inhibits melanosome transport in melan-a cells, especially
      at the melanosome transfer step from microtubles to actin filaments (i.e.
      perinuclear aggregation of melanosomes). On the basis of our findings, we propose
      that myosin-Va interacts with Slac2-a.Rab27A complex on the melanosome via two
      distinct domains, both of which are essential for melanosome transport in
      melanocytes.

PMID- 14730012
TI  - Mevalonate kinase is a cytosolic enzyme in humans.
AB  - In the past decade several reports have appeared which suggest that peroxisomes
      play a central role in isoprenoid/cholesterol biosynthesis. These suggestions
      were based primarily on the reported finding of several of the enzymes of the
      presqualene segment of the biosynthetic pathway in peroxisomes. More recently,
      however, conflicting results have been reported raising doubt about the
      postulated role of peroxisomes in isoprenoid biosynthesis, at least in humans. In
      this study we have studied the subcellular localisation of human mevalonate
      kinase (MK) using a variety of biochemical and microscopical techniques. These
      include conventional subcellular fractionation studies, digitonin
      permeabilisation studies, immunofluorescence microscopy and immunocytochemistry.
      We exclusively found a cytosolic localisation of both endogenous human MK (human
      fibroblasts, liver and HEK293 cells) and overexpressed human MK (human
      fibroblasts, HEK293 cells and CV1 cells). No indication of a peroxisomal
      localisation was obtained. Our results do not support a central role for
      peroxisomes in isoprenoid biosynthesis.

PMID- 14730013
TI  - The Varkud satellite ribozyme.
AB  - The VS ribozyme is the largest nucleolytic ribozyme, for which there is no
      crystal structure to date. The ribozyme consists of five helical sections,
      organized by two three-way junctions. The global structure has been determined by
      solution methods, particularly FRET. The substrate stem-loop binds into a cleft
      formed between two helices, while making a loop-loop contact with another section
      of the ribozyme. The scissile phosphate makes a close contact with an internal
      loop (the A730 loop), the probable active site of the ribozyme. This loop
      contains a particularly critical nucleotide A756. Most changes to this nucleotide
      lead to three-orders of magnitude slower cleavage, and the Watson-Crick edge is
      especially important. NAIM experiments indicate that a protonated base is
      required at this position for the ligation reaction. A756 is thus a strong
      candidate for nucleobase participation in the catalytic chemistry.

PMID- 14730015
TI  - Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes.
AB  - microRNAs (miRNAs) are 21-22-nucleotide noncoding RNAs that are widely believed
      to regulate complementary mRNA targets. However, due to the modest amount of
      pairing involved, only a few out of the hundreds of known animal miRNAs have thus
      far been connected to mRNA targets. Here, we considered the possibility that
      miRNAs might regulate non-mRNA targets, namely other miRNAs. To do so, we
      conducted a systematic assessment of the nearly complete catalogs of animal
      miRNAs for potential miRNA:miRNA complements. Our analysis uncovered several
      compelling examples that strongly suggest a function for miRNA duplexes, thus
      adding a potential layer of regulatory sophistication to the small RNA world.
      Interestingly, the most striking examples involve miRNAs complementary to members
      of the K-box family and Brd-box family, two classes of miRNAs previously
      implicated in regulation of Notch target genes. We emphasize that patterns of
      nucleotide constraint indicate that miRNA complementarity is not a simple
      consequence of miRNA:miRNA* complementarity; however, our findings do suggest
      that the potential regulatory consequences of the latter also deserve
      investigation.

PMID- 14730014
TI  - Mitochondrial proteins and complexes in Leishmania and Trypanosoma involved in U
      insertion/deletion RNA editing.
AB  - A number of mitochondrial proteins have been identified in Leishmania sp. and
      Trypanosoma brucei that may be involved in U-insertion/deletion RNA editing. Only
      a few of these have yet been characterized sufficiently to be able to assign
      functional names for the proteins in both species, and most have been denoted by
      a variety of species-specific and laboratory-specific operational names, leading
      to a terminology confusion both within and outside of this field. In this review,
      we summarize the present status of our knowledge of the orthologous and unique
      putative editing proteins in both species and the functional motifs identified by
      sequence analysis and by experimentation. An online Supplemental sequence
      database (http://164.67.60.200/proteins/protsmini1.asp) is also provided as a
      research resource.

PMID- 14730016
TI  - The three-dimensional architecture of the class I ligase ribozyme.
AB  - The class I ligase ribozyme catalyzes a Mg(++)-dependent RNA-ligation reaction
      that is chemically analogous to a single step of RNA polymerization. Indeed, this
      ribozyme constitutes the catalytic domain of an accurate and general RNA
      polymerase ribozyme. The ligation reaction is also very rapid in both single- and
      multiple-turnover contexts and thus is informative for the study of RNA catalysis
      as well as RNA self-replication. Here we report the initial characterization of
      the three-dimensional architecture of the ligase. When the ligase folds, several
      segments become protected from hydroxyl-radical cleavage, indicating that the RNA
      adopts a compact tertiary structure. Ribozyme folding was largely, though not
      completely, Mg(++) dependent, with a K(1/2[Mg]) < 1 mM, and was observed over a
      broad temperature range (20 degrees C -50 degrees C). The hydroxyl-radical
      mapping, together with comparative sequence analyses and analogy to a region
      within 23S ribosomal RNA, were used to generate a three-dimensional model of the
      ribozyme. The predictive value of the model was tested and supported by a photo
      cross-linking experiment.

PMID- 14730017
TI  - Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear
      export of pre-miRNAs.
AB  - microRNAs (miRNAs) are widespread among eukaryotes, and studies in several
      systems have revealed that miRNAs can regulate expression of specific genes.
      Primary miRNA transcripts are initially processed to approximately 70-nucleotide
      (nt) stem-loop structures (pre-miRNAs), exported to the cytoplasm, further
      processed to yield approximately 22-nt dsRNAs, and finally incorporated into
      ribonucleoprotein particles, which are thought to be the active species. Here we
      study nuclear export of pre-miRNAs and show that the process is saturable and
      thus carrier-mediated. Export is sensitive to depletion of nuclear RanGTP and,
      according to this criterion, mediated by a RanGTP-dependent exportin. An unbiased
      affinity chromatography approach with immobilized pre-miRNAs identified exportin
      5 as the pre-miRNA-specific export carrier. We have cloned exportin 5 from
      Xenopus and demonstrate that antibodies raised against the Xenopus receptor
      specifically block pre-miRNA export from nuclei of Xenopus oocytes. We further
      show that exportin 5 interacts with double-stranded RNA in a sequence-independent
      manner.

PMID- 14730018
TI  - Not all pseudouridine synthases are potently inhibited by RNA containing 5
      fluorouridine.
AB  - RNA containing 5-fluorouridine has been assumed to inhibit strongly or
      irreversibly the pseudouridine synthases that act on the RNA. RNA transcripts
      containing 5-fluorouridine in place of uridine have, therefore, been added to
      reconstituted systems in order to investigate the importance of particular
      pseudouridine residues in a given RNA by inactivating the pseudouridine synthase
      responsible for their generation. In sharp contradiction to the assumption of
      universal inhibition of pseudouridine synthases by RNA containing 5
      fluorouridine, the Escherichia coli pseudouridine synthase TruB, which has
      physiologically critical eukaryotic homologs, is not inhibited by such RNA.
      Instead, the RNA containing 5-fluorouridine was handled as a substrate by TruB.
      The E. coli pseudouridine synthase RluA, on the other hand, forms a covalent
      complex and is inhibited stoichiometrically by RNA containing 5-fluorouridine. We
      offer a hypothesis for this disparate behavior and urge caution in interpreting
      results from reconstitution experiments in which RNA containing 5-fluorouridine
      is assumed to inhibit a pseudouridine synthase, as normal function may result
      from a failure to inactivate the targeted enzyme rather than from the absence of
      nonessential pseudouridine residues.

PMID- 14730019
TI  - eIF4A3 is a novel component of the exon junction complex.
AB  - The exon junction complex (EJC) is a protein complex that assembles near exon
      exon junctions of mRNAs as a result of splicing. EJC proteins play important
      roles in postsplicing events including mRNA export, cytoplasmic localization, and
      nonsense-mediated decay. Recent evidence suggests that mRNA translation is also
      influenced by the splicing history of the transcript. Here we identify eIF4A3, a
      DEAD-box RNA helicase and a member of the eIF4A family of translation initiation
      factors, as a novel component of the EJC. We show that eIF4A3 associates
      preferentially with nuclear complexes containing the EJC proteins magoh and Y14.
      Furthermore, eIF4A3, but not the highly related eIF4A1 or eIF4A2, preferentially
      associates with spliced mRNA. In vitro splicing and mapping experiments
      demonstrate that eIF4A3 binds mRNAs at the position of the EJC. Using monoclonal
      antibodies, we show that eIF4A3 is found in the nucleus whereas eIF4A1 and eIF4A2
      are found in the cytoplasm. Thus, eIF4A3 likely provides a splicing-dependent
      influence on the translation of mRNAs.

PMID- 14730020
TI  - Definition of a spliceosome interaction domain in yeast Prp2 ATPase.
AB  - The Saccharomyces cerevisiae splicing factor Prp2 is an RNA-dependent ATPase
      required before the first transesterification reaction in pre-mRNA splicing. Prp2
      binds to the spliceosome in the absence of ATP and is released following ATP
      hydrolysis. It contains three domains: a unique N-terminal domain, a helicase
      domain that is highly conserved in the DExD/H protein family, and a C-terminal
      domain that is conserved in spliceosomal DEAH proteins Prp2, Prp16, Prp22, and
      Prp43. We examined the role of each domain of Prp2 by deletion mutagenesis.
      Whereas deletions of either the helicase or C-terminal domain are lethal,
      deletions in the N-terminal domain have no detectable effect on Prp2 activity.
      Overexpression of the C-terminal domain of Prp2 exacerbates the temperature
      sensitive phenotype of a prp2(Ts) strain, suggesting that the C-domain interferes
      with the activity of the Prp2(Ts) protein. A genetic approach was then taken to
      study interactions between Prp2 and the spliceosome. Previously, we isolated
      dominant negative mutants in the helicase domain of Prp2 that inhibit the
      activity of wild-type Prp2 when the mutant protein is overexpressed. We
      mutagenized one prp2 release mutant gene and screened for loss of dominant
      negative function. Several weak binding mutants were isolated and mapped to the C
      terminus of Prp2, further indicating the importance of the C terminus in
      spliceosome binding. This study is the first to indicate that amino acid
      substitutions outside the helicase domain can abolish spliceosome contact and
      splicing activity of a spliceosomal DEAH protein.

PMID- 14730021
TI  - P-site tRNA is a crucial initiator of ribosomal frameshifting.
AB  - The expression of some genes requires a high proportion of ribosomes to shift at
      a specific site into one of the two alternative frames. This utilized
      frameshifting provides a unique tool for studying reading frame control. Peptidyl
      tRNA slippage has been invoked to explain many cases of programmed frameshifting.
      The present work extends this to other cases. When the A-site is unoccupied, the
      P-site tRNA can be repositioned forward with respect to mRNA (although
      repositioning in the minus direction is also possible). A kinetic model is
      presented for the influence of both, the cognate tRNAs competing for overlapping
      codons in A-site, and the stabilities of P-site tRNA:mRNA complexes in the
      initial and new frames. When the A-site is occupied, the P-site tRNA can be
      repositioned backward. Whether frameshifting will happen depends on the ability
      of the A-site tRNA to subsequently be repositioned to maintain physical proximity
      of the tRNAs. This model offers an alternative explanation to previously
      published mechanisms of programmed frameshifting, such as out-of-frame tRNA
      binding, and a different perspective on simultaneous tandem tRNA slippage.

PMID- 14730022
TI  - Crystal structure of the catalytic domain of RluD, the only rRNA pseudouridine
      synthase required for normal growth of Escherichia coli.
AB  - Escherichia coli pseudouridine synthase RluD makes pseudouridines 1911, 1915, and
      1917 in the loop of helix 69 in 23S RNA. These are the most highly conserved
      ribosomal pseudouridines known. Of 11 pseudouridine synthases in E. coli, only
      cells lacking RluD have severe growth defects and abnormal ribosomes. We have
      determined the 2.0 A structure of the catalytic domain of RluD (residues 77-326),
      the first structure of an RluA family member. The catalytic domain folds into a
      mainly antiparallel beta-sheet flanked by several loops and helices. A positively
      charged cleft that presumably binds RNA leads to the conserved Asp 139. The RluD
      N-terminal S4 domain, connected by a flexible linker, is disordered in our
      structure. RluD is very similar in both catalytic domain structure and active
      site arrangement to the pseudouridine synthases RsuA, TruB, and TruA. We identify
      five sequence motifs, two of which are novel, in the RluA, RsuA, TruB, and TruA
      families, uniting them as one superfamily. These results strongly suggest that
      four of the five families of pseudouridine synthases arose by divergent
      evolution. The RluD structure also provides insight into its multisite
      specificity.

PMID- 14730024
TI  - The kink-turn motif in RNA is dimorphic, and metal ion-dependent.
AB  - The kink-turn (K-turn) is a new motif in RNA structure that was identified by
      examination of the crystal structures of the ribosome. We examined the structural
      and dynamic properties of this element in free solution. The K-turn RNA exists in
      a dynamic equilibrium between a tightly kinked conformation and a more open
      structure similar to a simple bulge bend. The highly kinked form is stabilized by
      the noncooperative binding of metal ions, but a significant population of the
      less-kinked form is present even in the presence of relatively high
      concentrations of divalent metal ions. The conformation of the tightly kinked
      population is in excellent agreement with that of the K-turn structures observed
      in the ribosome by crystallography. The end-to-end FRET efficiency of this
      species agrees closely with that of the ribosomal K-turn, and the direction of
      the bend measured by comparative gel electrophoresis also corresponds very well.
      These results show that the tightly kinked conformation of the K-turn requires
      stabilization by other factors, possibly by protein binding, for example. The K
      turn is therefore unlikely to be of itself a primary organizing feature in RNA.

PMID- 14730023
TI  - The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is
      essential in vivo but dispensable for activity in vitro.
AB  - The general splicing factor U2AF(65) recognizes the polypyrimidine tract (Py
      tract) that precedes 3' splice sites and has three RNA recognition motifs (RRMs).
      The C-terminal RRM (RRM3), which is highly conserved, has been proposed to
      contribute to Py-tract binding and establish protein-protein contacts with
      splicing factors mBBP/SF1 and SAP155. Unexpectedly, we find that the human RRM3
      domain is dispensable for U2AF(65) activity in vitro. However, it has an
      essential function in Schizosaccharomyces pombe distinct from binding to the Py
      tract or to mBBP/SF1 and SAP155. First, deletion of RRM3 from the human protein
      has no effect on Py-tract binding. Second, RRM123 and RRM12 select similar
      sequences from a random pool of RNA. Third, deletion of RRM3 has no effect on the
      splicing activity of U2AF(65) in vitro. However, deletion of the RRM3 domain of
      S. pombe U2AF(59) abolishes U2AF function in vivo. In addition, certain amino
      acid substitutions on the four-stranded beta-sheet surface of RRM3 compromise
      U2AF function in vivo without affecting binding to mBBP/SF1 or SAP155 in vitro.
      We propose that RRM3 has an unrecognized function that is possibly relevant for
      the splicing of only a subset of cellular introns. We discuss the implications of
      these observations on previous models of U2AF function.

PMID- 14730025
TI  - Preferential translation of cold-shock mRNAs during cold adaptation.
AB  - Upon temperature downshift below the lower threshold of balanced growth
      (approximately 20 degrees C), the Escherichia coli translational apparatus
      undergoes modifications allowing the selective translation of the transcripts of
      cold shock-induced genes, while bulk protein synthesis is drastically reduced.
      Here we were able to reproduce this translational bias in E. coli cell-free
      extracts prepared at various times during cold adaptation which were found to
      display different capacities to translate different types of mRNAs as a function
      of temperature. Several causes were found to contribute to the cold-shock
      translational bias: Cold-shock mRNAs contain cis-elements, making them
      intrinsically more prone to being translated in the cold, and they are selective
      targets for trans-acting factors present in increased amounts in the
      translational apparatus of cold-shocked cells. CspA was found to be among these
      trans-acting factors. In addition to inducing a higher level of CspA, cold shock
      was found to cause a strong (two- to threefold) stoichiometric imbalance of the
      ratio between initiation factors (IF1, IF2, IF3) and ribosomes without altering
      the stoichiometric ratio between the factors themselves. The most important
      sources of cold-shock translational bias is IF3, which strongly and selectively
      favors translation of cold-shock mRNAs in the cold. IF1 and the RNA chaperone
      CspA, which stimulate translation preferentially in the cold without mRNA
      selectivity, can also contribute to the translational bias. Finally, in contrast
      to a previous claim, translation of cold-shock cspA mRNA in the cold was found to
      be as sensitive as that of a non-cold-shock mRNA to both chloramphenicol and
      kanamycin inhibition.

PMID- 14730026
TI  - Localization of a promoter in the putative internal ribosome entry site of the
      Saccharomyces cerevisiae TIF4631 gene.
AB  - The 5'-region of the TIF4631 gene of Saccharomyces cerevisiae (encoding the
      translation initiation factor eIF4G1) was reported earlier to harbor a very
      active internal ribosome entry site (IRES) allowing for internal initiation of
      translation of TIF4631 mRNA. Here, we report the presence of a promoter in the
      region -112 to -36 relative to the translation initiation codon of the TIF4631
      gene. This promoter stimulates transcription from a start site at position -36
      and generates an mRNA that is actively translated in vitro and able to sustain
      growth of yeast cells in vivo as the only source of eIF4G. The data show that the
      IRES activity reported earlier is due to this promoter. On the contrary, the
      presumed IRES represents a strongly inhibitory element for translation in vitro.

PMID- 14730027
TI  - L-Myc protein synthesis is initiated by internal ribosome entry.
AB  - An internal ribosome entry segment (IRES) has been identified in the 5'
      untranslated region (5' UTR) of two members of the myc family of proto-oncogenes,
      c-myc and N-myc. Hence, the synthesis of c-Myc and N-Myc polypeptides can involve
      the alternative mechanism of internal initiation. Here, we show that the 5' UTR
      of L-myc, another myc family member, also contains an IRES. Previous studies have
      shown that the translation of mRNAs containing the c-myc and N-myc IRESs can
      involve both cap-dependent initiation and internal initiation. In contrast, the
      data presented here suggest that internal initiation can account for all of the
      translation initiation that occurs on an mRNA with the L-myc IRES in its 5' UTR.
      Like many other cellular IRESs, the L-myc IRES appears to be modular in nature
      and the entire 5' UTR is required for maximum IRES efficiency. The ribosome entry
      window within the L-myc IRES is located some distance upstream of the initiation
      codon, and thus, this IRES uses a "land and scan" mechanism to initiate
      translation. Finally, we have derived a secondary structural model for the IRES.
      The model confirms that the L-myc IRES is highly structured and predicts that a
      pseudoknot may form near the 5' end of the mRNA.

PMID- 14730028
TI  - Packaging and reverse transcription of snRNAs by retroviruses may generate
      pseudogenes.
AB  - Retroviruses specifically package two copies of their RNA genome in each viral
      particle, along with some small cellular RNAs, including tRNAs and 7S L RNA. We
      show here that Rous sarcoma virus (RSV) also packages U6 snRNA at approximately
      one copy per virion. In addition, trace amounts of U1 and U2 snRNAs were detected
      in purified virus by Northern blotting. U6 snRNA comigrated with the RSV 70S
      genomic RNA dimer on sucrose gradients. We observed reverse transcription of U6
      snRNA in an endogenous reaction in which RSV particles were the source of both
      reverse transcriptase and RNA substrates. This finding led us to examine
      mammalian genomic sequences for the presence of snRNA pseudogenes. A survey of
      the human, mouse, and rat genomes revealed a high number of spliceosomal snRNA
      pseudogenes. U6 pseudogenes were the most abundant, with approximately 200 copies
      in each genome. In the human genome, 67% of U6 snRNA pseudogenes, and a
      significant number of the other snRNA pseudogenes, were associated with LINE,
      SINE, or retroviral LTR repeat sequences. We propose that the packaging of snRNAs
      in retroviral particles leads to their reverse transcription in an infected cell
      and the integration of snRNA/viral recombinants into the host genome.

PMID- 14730029
TI  - Analysis of Snu13p mutations reveals differential interactions with the U4 snRNA
      and U3 snoRNA.
AB  - Pre-mRNA splicing is executed by the spliceosome, a complex of small nuclear RNAs
      (snRNAs) and numerous proteins. One such protein, 15.5K/Snu13p, is associated
      with the spliceosomal U4/U6.U5 tri-snRNP and box C/D small nucleolar
      ribonucleoprotein particles (snoRNPs), which act during preribosomal RNA (rRNA)
      processing. As such, it is the first splicing factor to be identified in two
      functionally distinct particles. 15.5K binds to an internal helix-bulge-helix (K
      turn) structure in the U4 snRNA and two such structures in the U3 snoRNA.
      Previous work has concentrated on the structural basis of the interaction of
      15.5K with the RNAs and has been carried out in vitro. Here we present a
      functional analysis of Snu13p in vivo, using a galactose inducible SNU13 strain
      to investigate the basis of three lethal mutations in Saccharomyces cerevisiae.
      Two are point mutations that map to the RNA-binding domain, and the third is a C
      terminal deletion. These mutations result in accumulation of unspliced pre-mRNA,
      confirming a role for Snu13p in pre-mRNA splicing. In addition, these mutants
      also display rRNA processing defects that are variable in nature. Analysis of one
      mutant in the RNA-binding domain reveals a reduction in the levels of the U4
      snRNA, U6 snRNA, and box C/D snoRNAs, but not H/ACA snoRNAs, supporting a role
      for Snu13p in accumulation and/or maintenance of specific RNAs. The mutations in
      the RNA-binding domain exhibit differential binding to the U4 snRNA and U3 snoRNA
      in vitro, suggesting that there are differences in the mode of interaction of
      Snu13p with these two RNAs.

PMID- 14730030
TI  - Two-step affinity purification of the hepatitis C virus ribonucleoprotein
      complex.
AB  - Positive-strand RNA viruses replicate their RNA genome within a ribonucleoprotein
      (RNP) complex that is associated with cellular membranes. We used a two-step
      method of purification to isolate hepatitis C virus (HCV) RNP complexes from
      human hepatoma cell line Huh7, which stably expresses HCV subgenomic replicons.
      The procedure involved hybridization of replicon-expressing cellular lysates with
      oligonucleotides tagged with biotin and digoxigenin at their respective termini
      complementary to subgenomic replicon RNA followed by avidin-agarose enrichment of
      the mixture and subsequent immunoprecipitation of biotin-eluted material with
      anti-digoxigenin antibody. The immunoprecipitates were immunoblotted with
      antisera against HCV nonstructural (NS) proteins. The analysis revealed the
      association of all the HCV NS proteins (NS3, NS4a, NS4b, NS5a, and NS5b) that are
      encoded by the subgenomic replicon RNA. The HCV RNP complex migrated in a native
      polyacrylamide gel with an approximate molecular mass of 450 kD. The association
      of these viral proteins in the RNP complex reinforces the widely acknowledged
      notion that RNA viruses accomplish replication within a membranous RNP complex.

PMID- 14730031
TI  - Focal nodular hyperplasia: findings at state-of-the-art MR imaging, US, CT, and
      pathologic analysis.
AB  - Focal nodular hyperplasia (FNH) is the second most common benign liver tumor
      after hemangioma. FNH is classified into two types: classic (80% of cases) and
      nonclassic (20%). Distinction between FNH and other hypervascular liver lesions
      such as hepatocellular adenoma, hepatocellular carcinoma, and hypervascular
      metastases is critical to ensure proper treatment. An asymptomatic patient with
      FNH does not require biopsy or surgery. Magnetic resonance (MR) imaging has
      higher sensitivity and specificity for FNH than does ultrasonography or computed
      tomography. Typically, FNH is iso- or hypointense on T1-weighted images, is
      slightly hyper- or isointense on T2-weighted images, and has a hyperintense
      central scar on T2-weighted images. FNH demonstrates intense homogeneous
      enhancement during the arterial phase of gadolinium-enhanced imaging and
      enhancement of the central scar during later phases. Familiarity with the proper
      MR imaging technique and the spectrum of MR imaging findings is essential for
      correct diagnosis of FNH.

PMID- 14730033
TI  - TIPS-related hepatic encephalopathy: management options with novel endovascular
      techniques.
AB  - Hepatic encephalopathy is a common complication that develops after creation of a
      transjugular intrahepatic portosystemic shunt (TIPS). Although most patients
      respond well to conservative medical therapy (ie, protein-restricted diet,
      nonabsorbable disaccharides, nonabsorbable antibiotics), a small percentage of
      patients (3%-7%) do not benefit from these methods and require more invasive
      therapeutic approaches. One option is emergent liver transplantation, but the
      majority of patients are not suitable candidates. Recently, various percutaneous
      techniques have been described that alter the hemodynamics through the shunt by
      occluding it with coils or balloons or by reducing its diameter by inserting
      constrained stents or stent-grafts. Other techniques have been used for patients
      with TIPS-related hepatic encephalopathy in whom spontaneous splenorenal shunts
      are present. In many patients with refractory hepatic encephalopathy, these
      percutaneous techniques have produced symptomatic improvement, with either a
      complete resolution or a substantial reduction in hepatic encephalopathy symptoms
      that can be controlled with medical therapy. Unfortunately, despite all attempts,
      some patients remain incapacitated and ultimately die. Further research is
      necessary to improve our understanding of TIPS-related hepatic encephalopathy so
      that newer, less invasive and safer procedures can be developed to treat this
      difficult clinical problem.

PMID- 14730035
TI  - Radiofrequency thermal ablation of abdominal tumors: lessons learned from
      complications.
AB  - Radiofrequency (RF) thermal ablation has shown promise as a technique for
      treating inoperable solid tumors involving the liver, kidney, adrenal gland, and
      lung. However, like all other imaging-guided interventional procedures, RF
      ablation involves some element of risk. Varying degrees of complications can be
      expected, depending on factors such as the organ site and the aggressiveness of
      the procedure. General complications of RF ablation may be related to either
      imaging-guided electrode placement (eg, bleeding, infection, tumor seeding,
      pneumothorax) or thermal therapy (eg, nontarget thermal damage, grounding pad
      burns). Liver and renal-adrenal ablation may be associated with organ-specific
      complications. A fundamental understanding of RF ablation principles, along with
      adequate operator training and experience and familiarity with both thermal
      ablation and the broad spectrum of postablation complications, are necessary to
      maximize the safety and efficacy of this procedure. The standard of care for
      decreasing the morbidity of complications consists of prevention (including
      careful patient selection), early detection, and prompt, appropriate treatment.

PMID- 14730036
TI  - Intraductal papillary mucinous tumor of the bile ducts.
AB  - Papillary tumors of the bile ducts are intraductal tumors with numerous minute
      frondlike papillary projections. Some intraductal papillary tumors of the bile
      ducts produce a large amount of mucin that disturbs bile flow and causes severe
      biliary dilatation. In the presence of a tumor of this subgroup, the entire
      biliary tree is dilated; segmental or lobar bile ducts are dilated
      disproportionately, and aneurysmal dilatation may occur. Mucin is depicted at
      cholangiography as multiple elongated or cordlike filling defects, and the tumor
      is depicted on cross-sectional images as a castlike, polypoid, or fungating mass
      in the dilated biliary tree. Based on these characteristic imaging features
      dilatation, mucin, and tumor-correct diagnosis of intraductal papillary mucinous
      tumor of the bile ducts may be made.

PMID- 14730038
TI  - MR imaging and MR arthrography of the postoperative shoulder: spectrum of normal
      and abnormal findings.
AB  - The postoperative shoulder may be evaluated with various imaging modalities,
      including radiography, ultrasonography, computed tomography, and magnetic
      resonance (MR) imaging, each of which has advantages and disadvantages. For
      optimal soft-tissue visualization, MR imaging and MR arthrography are widely
      used. Several factors, however, may decrease the accuracy of MR imaging in the
      evaluation of the postoperative shoulder. These factors include surgical
      distortions of native anatomy, changes in the signal intensity of tissues, and
      image degradation caused by metallic artifacts. To maximize the accuracy of MR
      imaging, the radiologist must select the most appropriate pulse sequences and
      techniques for the given anatomic structure and the suspected postoperative
      condition. To avoid magnetic susceptibility artifacts at MR imaging, inversion
      recovery may be used instead of fat saturation, and fast spin-echo sequences may
      be used instead of conventional spin-echo sequences or gradient-echo sequences.
      MR arthrography is most useful for optimal delineation of the rotator cuff,
      capsulolabral structures, and tendon defects. To achieve accurate image
      interpretation, the radiologist must be familiar with the arthroscopic and the
      open surgical techniques currently used to repair internal derangements of the
      glenohumeral joint, as well as with the typical imaging findings in each
      postoperative situation.

PMID- 14730039
TI  - Radiologic manifestations of sarcoidosis in various organs.
AB  - Sarcoidosis is a systemic disorder of unknown cause with a wide variety of
      clinical and radiologic manifestations. The diagnosis is usually made on the
      basis of these manifestations supported by histologic findings. Systemic
      manifestations (eg, Lofgren syndrome, Heerfordt syndrome) are commonly seen at
      clinical examination. Bilateral hilar lymphadenopathy is the most common
      radiologic finding-frequently with associated pulmonary infiltrates-and typically
      has a characteristic perivascular distribution at high-resolution chest computed
      tomography. Radiologic findings in the short tubular bones of the hands and feet
      and magnetic resonance imaging findings of nodular involvement of muscle are
      often sufficient to raise suspicion for sarcoidosis. In the liver, spleen,
      kidneys, and scrotum, coalescing granulomas form nodules whose imaging features
      may occasionally be nonspecific, although familiarity with the relevant clinical
      settings will be helpful in recognizing the presence of sarcoidosis. Radiologic
      recognition of cardiac and central nervous system involvement is also important
      because patients may be only mildly symptomatic. The clinical course and
      prognosis of sarcoidosis are highly variable, often correlating with the mode of
      onset. Familiarity with the clinical and radiologic features of sarcoidosis in
      various anatomic locations plays a crucial role in diagnosis and management.

PMID- 14730041
TI  - Clinical breast lymphoscintigraphy: optimal techniques for performing studies,
      image atlas, and analysis of images.
AB  - Breast lymphoscintigraphy is increasingly performed before surgery to delineate
      the drainage to the sentinel node (SN) in the axilla. On the basis of the
      histologic status of harvested SNs, the disease status of the entire axilla can
      be predicted. This prediction allows a more limited dissection to be performed
      while maintaining staging accuracy comparable with that of classic axillary lymph
      node dissection. Lymphoscintigraphy assists surgeons in harvesting the SN during
      gamma probe-assisted axillary biopsy or dissection and provides a wide field of
      view survey, among other benefits. When certain injection protocols are used,
      lymphoscintigraphy can be performed in the afternoon before surgery the next
      morning, thus minimizing disruptions of tight surgical schedules. Image
      acquisition can be optimized and SN activity can be maximized by means of such
      factors as parameters for preparation of the radiotracer, injection techniques,
      energy settings for the gamma camera, breast displacement maneuvers, and
      techniques for marking and outlining the patient's body. The ultimate goals are
      to delineate the true SN, maximize activity in the node for facilitated removal
      (even at next-day surgery), and deliver the information to the surgeon without
      delaying the surgical schedule.

PMID- 14730040
TI  - Malignant pleural mesothelioma: evaluation with CT, MR imaging, and PET.
AB  - Imaging plays an essential role in the evaluation of malignant pleural
      mesothelioma (MPM). Computed tomography is the primary imaging modality used for
      the diagnosis and staging of MPM. Magnetic resonance (MR) imaging and, more
      recently, positron emission tomography (PET) have emerged as modalities that can
      provide additional important diagnostic and prognostic information to help
      further delineate the extent of disease, especially in surgical candidates. Use
      of MR imaging performed with different pulse sequences and gadolinium-based
      contrast material can improve the detection of tumor extension, especially to the
      chest wall and diaphragm. PET can provide both anatomic and metabolic
      information, especially in cases of extrathoracic and mediastinal nodal
      metastasis. Each imaging modality has its advantages and limitations, but their
      combined use is crucial in determining the most appropriate treatment options for
      patients with MPM.

PMID- 14730043
TI  - Recognizing pitfalls in early and late migration of clip markers after imaging
      guided directional vacuum-assisted biopsy.
AB  - Directional vacuum-assisted biopsy has become an irreplaceable tool in the
      management of suspicious mammographic lesions. Often, the entire lesion is
      removed and clips are used to localize the biopsy site. Postbiopsy mammograms are
      used to determine the adequacy of clip placement and the location of the clip.
      Clip displacement from the site of deployment is not an uncommon finding. Clips
      may migrate within the same quadrant where the lesion was located or to another
      quadrant of the breast. Clip migration may occur immediately after biopsy or may
      be seen on later follow-up mammograms. Clip migration can affect interpretation
      of mammographic findings and localization for future surgery. It should not be
      assumed that the clip is correctly located at the biopsy site on subsequent
      mammograms. It is essential to recognize the relationship of the clip to the
      targeted lesion to ensure accurate localization of lesions that require surgical
      excision.

PMID- 14730044
TI  - Detection of fetal structural abnormalities with US during early pregnancy.
AB  - Ultrasonography (US) is performed during early pregnancy for dating,
      determination of the number of fetuses, assessment of early complications, and
      increasingly for evaluation of the fetus, including measurement of the thickness
      of the nuchal translucency (NT). Measurement of NT thickness between 11 and 14
      weeks gestation, combined with maternal age and maternal serum biochemistry, can
      be an effective method of screening for trisomy 21 and other chromosomal
      abnormalities. Furthermore, an increased NT thickness in the presence of a normal
      karyotype is associated with an increased frequency of structural defects and
      genetic syndromes. Therefore, this finding is an indication for a more detailed
      anatomic survey of the fetus. Besides nuchal abnormalities, a wide range of other
      congenital anomalies can be diagnosed with US at 11-14 weeks gestation, including
      defects of the central nervous system, heart, anterior abdominal wall, urinary
      tract, and skeleton. The anatomic survey can be performed with a standardized
      protocol by using transabdominal US and, when necessary, transvaginal US. A
      thorough knowledge of the US features of normal fetal development is necessary to
      avoid potential diagnostic pitfalls.

PMID- 14730045
TI  - Various approaches for CT-guided percutaneous biopsy of deep pelvic lesions:
      anatomic and technical considerations.
AB  - Access route planning for computed tomography-guided biopsy of deep pelvic masses
      remains challenging because vital structures often obstruct the projected needle
      path. The classical approach through the lower anterior abdominal wall allows
      access to lesions located anterior, superior, or lateral to the urinary bladder.
      However, this approach has limitations: Deep masses are difficult to reach
      because of intervening structures, the bowel or bladder may be unavoidably
      traversed, and peritoneal transgression is often painful. A transgluteal approach
      is useful for biopsy of presacral and perirectal lesions and lesions located
      posterolateral to the bladder. An anterolateral approach through the iliopsoas
      muscle allows safe extraperitoneal access to external and internal iliac nodes,
      masses located along the lateral pelvic sidewall, and adnexal lesions. A
      transosseous (transsacral or transiliac) approach can occasionally be used for
      otherwise inaccessible lesions. Use of a curved needle, change in patient
      position, or injection of saline solution to displace intervening structures may
      also be helpful. Familiarity with normal cross-sectional pelvic anatomy
      facilitates planning of a safe access route and helps avoid injury to adjacent
      structures. A thorough understanding of the advantages and disadvantages of each
      approach allows the clinician to choose the most appropriate approach in a given
      situation.

PMID- 14730046
TI  - Vascular dilatation in the pelvis: identification with CT and MR imaging.
AB  - Focal or diffuse dilatation of pelvic vessels is observed occasionally on
      computed tomographic or magnetic resonance images. Two major mechanisms may
      account for dilatation. The first mechanism is development of collateral channels
      as a result of venous obstruction or stenosis. Symptoms associated with vessel
      dilatation vary according to the level of obstruction. Portal hypertension also
      may result in the formation of numerous collateral vessels. In addition, left
      renal venous compression between the aorta and the superior mesenteric artery,
      which results in blood flow from the left renal vein toward the left gonadal
      vein, causes a variety of symptoms. The second major mechanism for dilatation is
      increased blood flow through collateral vessels associated with a neoplasm or
      vascular lesion. Hypervascular pelvic tumors such as uterine leiomyomas,
      gestational trophoblastic neoplasms, ovarian solid tumors, and mesenteric tumors
      may be associated with a marked increase in the number of draining vessels. The
      assessment of such vessels can assist in identification of tumor origins. Visual
      recognition of abnormal pelvic vasculature and abnormal hemodynamics is
      clinically important because it helps to improve diagnosis of a wide variety of
      pelvic and systemic diseases. Moreover, recognition of abnormal hemodynamics
      facilitates understanding of the physiology of such conditions. Recognition of
      the pattern of collateral channels also assists in identification of the level of
      narrowing even when the level is not readily apparent and is dependent on
      postural position.

PMID- 14730047
TI  - PET-CT in recurrent ovarian cancer: initial observations.
AB  - Noninvasive diagnosis of early recurrence of ovarian cancer is challenging due to
      the small size of peritoneal metastases. Small-volume disease may not be evident
      at anatomic imaging in patients with elevated serum tumor markers. Functional
      imaging in the form of positron emission tomography (PET) can help identify
      patients with recurrent tumor. However, lesion localization for possible surgical
      treatment is difficult with PET alone. Combined functional-anatomic imaging with
      fused PET and computed tomographic (CT) scans is feasible and may improve disease
      detection by increasing radiologic sensitivity and specificity. PET and PET-CT
      have a potential role in evaluating patients for recurrent ovarian cancer,
      particularly those with negative CT or magnetic resonance imaging findings and
      rising tumor marker levels. Fused PET-CT scans obtained with combined scanners
      can help localize pathologic activity and differentiate this activity from
      physiologic radiotracer uptake. Combined functional-anatomic imaging can also
      increase diagnostic confidence at CT. Further study is needed to determine the
      possible benefits of lesion conspicuity at PET and anatomic localization at CT on
      fused PET-CT scans.

PMID- 14730048
TI  - From the archives of the AFIP: radiologic staging of ovarian carcinoma with
      pathologic correlation.
AB  - Ovarian cancer is the deadliest gynecologic malignancy, with approximately 70% of
      patients having peritoneal involvement at the time of diagnosis. It spreads
      predominantly by direct invasion and intraperitoneal dissemination. The staging
      system is surgically based, with stage I disease being limited to one or both
      ovaries. In stage II disease, there is extraovarian spread of tumor, but it does
      not extend beyond the pelvis. Stages III and IV disease are considered advanced,
      with stage III ovarian cancer including diffuse peritoneal disease involving the
      upper abdomen and stage IV disease having distant metastases including hepatic
      lesions. Common sites of intraperitoneal seeding include the omentum, paracolic
      gutters, liver capsule, and diaphragm. Thickening, nodularity, and enhancement
      are all signs of peritoneal involvement. Although computed tomography is the most
      common imaging modality used to stage ovarian cancer, magnetic resonance imaging
      has been shown to be equally accurate. Currently, however, no imaging modality
      allows microscopic spread of disease to be ruled out, and a full staging
      laparotomy is always required. Early ovarian cancer is treated with comprehensive
      staging laparotomy, whereas advanced but operable disease is treated with primary
      cytoreductive surgery (debulking) followed by adjuvant chemotherapy. Patients
      with unresectable disease may benefit from neoadjuvant (preoperative)
      chemotherapy before debulking.

PMID- 14730049
TI  - Best cases from the AFIP: multicystic mesothelioma.

PMID- 14730050
TI  - Renal tuberculosis.

PMID- 14730051
TI  - Medical devices of the head, neck, and spine.
AB  - There are many medical devices used for head, neck, and spinal diseases and
      injuries, and new devices are constantly being introduced. Many of the newest
      devices are variations on a previous theme. Knowing the specific name of a device
      is not important. It is important to recognize the presence of a device and to
      have an understanding of its function as well as to be able to recognize the
      complications associated with its use. The article discusses the most common and
      important devices of the head, neck, and spine, including cerebrospinal fluid
      shunts and the Codman Hakim programmable valve; subdural drainage catheters,
      subdural electrodes, intracranial electrodes, deep brain stimulators, and
      cerebellar electrodes; coils, balloons, adhesives, particles, and aneurysm clips;
      radiation therapy catheters, intracranial balloons for drug installation, and
      carmustine wafers; hearing aids, cochlear implants, and ossicular reconstruction
      prostheses; orbital prostheses, intraocular silicone oil, and lacrimal duct
      stents; anterior and posterior cervical plates, posterior cervical spine wiring,
      odontoid fracture fixation devices, cervical collars and halo vests; thoracic and
      lumbar spine implants, anterior and posterior instrumentation for the thoracic
      and lumbar spine, vertebroplasty, and artificial disks; spinal column
      stimulators, bone stimulators, intrathecal drug delivery pumps, and sacral
      stimulators; dental and facial implant devices; gastric and tracheal tubes; vagus
      nerve stimulators; lumboperitoneal shunts; and temperature- and oxygen-sensing
      probes.

PMID- 14730052
TI  - New vessel analysis tool for morphometric quantification and visualization of
      vessels in CT and MR imaging data sets.
AB  - Image processing algorithms and a prototypical research software tool have been
      developed for visualization and quantitative analysis of vessels in data sets
      from computed tomography and magnetic resonance imaging. The software is based on
      a sequence of processing steps, which are as follows: (a) vessel segmentation
      based on a region growing algorithm, (b) interactive "premasking" to optionally
      exclude interfering structures close to the vessels of interest, (c) distance
      transform-based skeletonization, (d) multiplanar reformation orthogonal to the
      vessel path, (e) identification of the lumen boundary on the orthogonal cross
      section images, and (f) morphometric measurements. The development of the
      algorithmic components and the application user interface has been carried out in
      close cooperation with clinical users to achieve a high degree of usability and
      flexible support of work flow. The software has been successfully applied to the
      intracranial arteries, carotid arteries, and abdominal and thoracic aorta, as
      well as the renal, coronary, and peripheral arteries.

PMID- 14730053
TI  - Radiology on handheld devices: image display, manipulation, and PACS integration
      issues.
AB  - Handheld personal digital assistants (PDAs) have undergone continuous and
      substantial improvements in hardware and graphics capabilities, making them a
      compelling platform for novel developments in teleradiology. The latest PDAs have
      processor speeds of up to 400 MHz and storage capacities of up to 80 Gbytes with
      memory expansion methods. A Digital Imaging and Communications in Medicine
      (DICOM)-compliant, vendor-independent handheld image access system was developed
      in which a PDA server acts as the gateway between a picture archiving and
      communication system (PACS) and PDAs. The system is compatible with most
      currently available PDA models. It is capable of both wired and wireless transfer
      of images and includes custom PDA software and World Wide Web interfaces that
      implement a variety of basic image manipulation functions. Implementation of this
      system, which is currently undergoing debugging and beta testing, required
      optimization of the user interface to efficiently display images on smaller PDA
      screens. The PDA server manages user work lists and implements compression and
      security features to accelerate transfer speeds, protect patient information, and
      regulate access. Although some limitations remain, PDA-based teleradiology has
      the potential to increase the efficiency of the radiologic work flow, increasing
      productivity and improving communication with referring physicians and patients.

PMID- 14730054
TI  - Scenes from the past: presentation silver: loving cup of the Canadian Association
      of Radiologists.

PMID- 14730055
TI  - AAPM/RSNA tutorial on equipment selection: PACS equipment overview: general
      guidelines for purchasing and acceptance testing of PACS equipment.
AB  - A picture archiving and communication system (PACS) is a comprehensive computer
      system that is responsible for the electronic storage and distribution of medical
      images in the medical enterprise. The system is highly integrated with digital
      acquisition and display devices and is often related closely to other medical
      information systems, such as the radiology information system or hospital
      information system. In the past few years, there has been continuous growth in
      clinical implementation of PACS to reduce costs and improve patient care, a trend
      that is expected to continue. However, a PACS is complex and costly to acquire,
      replace, maintain, and repair. To select a system that best meets their
      requirements, purchasers of PACS equipment need to be aware of the key
      characteristics and differing features of the various products. After the PACS
      has been installed, the user should perform technical and clinical acceptance
      testing to ensure that the system meets expectations.

PMID- 14730056
TI  - Multi-detector row CT of the kidneys and urinary tract: techniques and
      applications in the diagnosis of benign diseases.
AB  - Multi-detector row helical computed tomography (CT) offers considerable
      advantages in evaluation of the urinary tract. It has the potential to become the
      single imaging modality used for comprehensive evaluation and treatment planning
      of most conditions affecting the kidneys and urinary tract, making conventional
      diagnostic techniques such as intravenous urography and angiography nearly
      obsolete. This article illustrates important selected applications of
      multidetector CT in the evaluation of benign conditions of the kidneys and upper
      urinary tract, including evaluation of the renal arterial and venous anatomy in
      preparation for surgery, diagnosis of renal artery stenosis and aneurysms,
      assessment of the renal veins, imaging of inflammatory and infectious renal
      diseases and evaluation of selected benign pathologic processes of the urinary
      tract.

PMID- 14730057
TI  - Automated array-based genomic profiling in chronic lymphocytic leukemia:
      development of a clinical tool and discovery of recurrent genomic alterations.
AB  - B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable
      clinical course. Recurrent chromosomal imbalances provide significant prognostic
      markers. Risk-adapted therapy based on genomic alterations has become an option
      that is currently being tested in clinical trials. To supply a robust tool for
      such large scale studies, we developed a comprehensive DNA microarray dedicated
      to the automated analysis of recurrent genomic imbalances in B-CLL by array-based
      comparative genomic hybridization (matrix-CGH). Validation of this chip in a
      series of 106 B-CLL cases revealed a high specificity and sensitivity that
      fulfils the criteria for application in clinical oncology. This chip is
      immediately applicable within clinical B-CLL treatment trials that evaluate
      whether B-CLL cases with distinct chromosomal abnormalities should be treated
      with chemotherapy of different intensities and/or stem cell transplantation.
      Through the control set of DNA fragments equally distributed over the genome,
      recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain
      of the MYCN oncogene correlating with an elevation of MYCN mRNA expression.

PMID- 14730058
TI  - Production, identity preservation, and labeling in a marketplace with genetically
      modified and non-genetically modified foods.

PMID- 14730059
TI  - Publications from industry. Personal and corporate incentives.

PMID- 14730061
TI  - Relocalization of the PIN1 auxin efflux facilitator plays a role in phototropic
      responses.

PMID- 14730060
TI  - Gene trapping with firefly luciferase in Arabidopsis. Tagging of stress
      responsive genes.
AB  - To monitor the expression of T-DNA-tagged plant genes in vivo, a collection of
      20,261 transgenic lines of Arabidopsis (Columbia-0) were generated with the
      promoter trap vector pTluc, which carries a promoterless firefly luc (luciferase)
      reporter gene linked to the right T-DNA border. By detection of bioluminescence
      in 3-week-old seedlings, 753 lines were identified showing constitutive, organ
      specific, and stress-responsive luciferase expression patterns. To facilitate the
      identification of well-defined luciferase expression patterns, a pooled seed
      stock was established. Several lines showed sugar, salt, and abscisic acid (ABA)
      inducible luciferase activity. Segregation analysis of 215 promoter trap lines
      indicated that about 50% of plants contained single insertions, whereas 40%
      carried two and 10% carried three or more T-DNA tags. Sequencing the T-DNA insert
      junctions isolated from 17 luciferase-expressing lines identified T-DNA tags in
      5'- and 3'-transcribed domains and translational gene fusions generated by T-DNA
      insertions in exons and introns of Arabidopsis genes. Tissue specific expression
      of eight wild-type Arabidopsis genes was confirmed to be similar to the
      luminescence patterns observed in the corresponding luciferase-tagged lines.
      Here, we describe the characterization of a transcriptional luc reporter gene
      fusion with the WBC-type ABC transporter gene At1g17840. Expression of wild-type
      and luciferase-tagged At1g17840 alleles revealed similar induction by salt,
      glucose, and ABA treatments and gibberellin-mediated down-regulation of ABA
      induced expression. These results illustrate that luciferase gene traps are well
      suited for monitoring the expression of stress-responsive Arabidopsis genes in
      vivo.

PMID- 14730062
TI  - On the mechanism of xylem vessel length regulation.

PMID- 14730063
TI  - Is petal senescence due to sugar starvation?

PMID- 14730064
TI  - Calcium sensors and their interacting protein kinases: genomics of the
      Arabidopsis and rice CBL-CIPK signaling networks.
AB  - Calcium signals mediate a multitude of plant responses to external stimuli and
      regulate a wide range of physiological processes. Calcium-binding proteins, like
      calcineurin B-like (CBL) proteins, represent important relays in plant calcium
      signaling. These proteins form a complex network with their target kinases being
      the CBL-interacting protein kinases (CIPKs). Here, we present a comparative
      genomics analysis of the full complement of CBLs and CIPKs in Arabidopsis and
      rice (Oryza sativa). We confirm the expression and transcript composition of the
      10 CBLs and 25 CIPKs encoded in the Arabidopsis genome. Our identification of 10
      CBLs and 30 CIPKs from rice indicates a similar complexity of this signaling
      network in both species. An analysis of the genomic evolution suggests that the
      extant number of gene family members largely results from segmental duplications.
      A phylogenetic comparison of protein sequences and intron positions indicates an
      early diversification of separate branches within both gene families. These
      branches may represent proteins with different functions. Protein interaction
      analyses and expression studies of closely related family members suggest that
      even recently duplicated representatives may fulfill different functions. This
      work provides a basis for a defined further functional dissection of this
      important plant-specific signaling system.

PMID- 14730065
TI  - The Arabidopsis root transcriptome by serial analysis of gene expression. Gene
      identification using the genome sequence.
AB  - Large-scale identification of genes expressed in roots of the model plant
      Arabidopsis was performed by serial analysis of gene expression (SAGE), on a
      total of 144,083 sequenced tags, representing at least 15,964 different mRNAs.
      For tag to gene assignment, we developed a computational approach based on 26,620
      genes annotated from the complete sequence of the genome. The procedure selected
      warrants the identification of the genes corresponding to the majority of the
      tags found experimentally, with a high level of reliability, and provides a
      reference database for SAGE studies in Arabidopsis. This new resource allowed us
      to characterize the expression of more than 3,000 genes, for which there is no
      expressed sequence tag (EST) or cDNA in the databases. Moreover, 85% of the tags
      were specific for one gene. To illustrate this advantage of SAGE for functional
      genomics, we show that our data allow an unambiguous analysis of most of the
      individual genes belonging to 12 different ion transporter multigene families.
      These results indicate that, compared with EST-based tag to gene assignment, the
      use of the annotated genome sequence greatly improves gene identification in SAGE
      studies. However, more than 6,000 different tags remained with no gene match,
      suggesting that a significant proportion of transcripts present in the roots
      originate from yet unknown or wrongly annotated genes. The root transcriptome
      characterized in this study markedly differs from those obtained in other organs,
      and provides a unique resource for investigating the functional specificities of
      the root system. As an example of the use of SAGE for transcript profiling in
      Arabidopsis, we report here the identification of 270 genes differentially
      expressed between roots of plants grown either with NO3- or NH4NO3 as N source.

PMID- 14730066
TI  - The ULTRACURVATA2 gene of Arabidopsis encodes an FK506-binding protein involved
      in auxin and brassinosteroid signaling.
AB  - The dwarf ucu (ultracurvata) mutants of Arabidopsis display vegetative leaves
      that are spirally rolled downwards and show reduced expansion along the
      longitudinal axis. We have previously determined that the UCU1 gene encodes a
      SHAGGY/GSK3-like kinase that participates in the signaling pathways of auxins and
      brassinosteroids. Here, we describe four recessive alleles of the UCU2 gene,
      whose homozygotes display helical rotation of several organs in addition to other
      phenotypic traits shared with ucu1 mutants. Following a map-based strategy, we
      identified the UCU2 gene, which was found to encode a peptidyl-prolyl cis/trans
      isomerase of the FK506-binding protein family, whose homologs in metazoans are
      involved in cell signaling and protein trafficking. Physiological and double
      mutant analyses suggest that UCU2 is required for growth and development and
      participates in auxin and brassinosteroid signaling.

PMID- 14730067
TI  - Phosphatidic acid induces leaf cell death in Arabidopsis by activating the Rho
      related small G protein GTPase-mediated pathway of reactive oxygen species
      generation.
AB  - Phosphatidic acid (PA) level increases during various stress conditions. However,
      the physiological roles of this lipid in stress response remain largely unknown.
      In this study, we report that PA induced leaf cell death and elevated the levels
      of reactive oxygen species (ROS) in the whole leaf and single cells. To further
      elucidate the mechanism of PA-induced cell death, we then examined whether Rho
      related small G protein (ROP) 2, which enhanced ROS production in an in vitro
      assay, is involved in PA-induced ROS production and cell death. In response to
      PA, transgenic leaves of Arabidopsis expressing a constitutively active rop2
      mutant exhibited earlier cell death and higher levels of ROS than wild type (WT),
      whereas those expressing a dominant-negative rop2 mutant exhibited later cell
      death and lower ROS. However, in the absence of exogenous PA, no spontaneous cell
      death or elevated ROS was observed in constitutively active rop2 plants,
      suggesting that the activation of ROP GTPase alone is insufficient to activate
      the ROP-mediated ROS generation pathway. These results suggest that PA modulates
      an additional factor required for the active ROP-mediated ROS generation pathway.
      Therefore, PA may be an important regulator of ROP-regulated ROS generation and
      the cell death process during various stress and defense responses of plants.

PMID- 14730068
TI  - AmSUT1, a sucrose transporter in collection and transport phloem of the putative
      symplastic phloem loader Alonsoa meridionalis.
AB  - A sucrose (Suc) transporter cDNA has been cloned from Alonsoa meridionalis, a
      member of the Scrophulariaceae. This plant species has an open minor vein
      configuration and translocates mainly raffinose and stachyose in addition to Suc
      in the phloem (C. Knop, O. Voitsekhovskaja, G. Lohaus [2001] Planta 213: 80-91).
      These are typical properties of symplastic phloem loaders. For functional
      characterization, AmSUT1 cDNA was expressed in bakers' yeast (Saccharomyces
      cerevisiae). Substrate and inhibitor specificities, energy dependence, and Km
      value of the protein agree well with the properties measured for other Suc
      transporters of apoplastic phloem loaders. A polyclonal antiserum against the 17
      N-terminal amino acids of the A. meridionalis Suc transporter AmSUT1 was used to
      determine the cellular localization of the AmSUT1 protein. Using fluorescence
      labeling on sections from A. meridionalis leaves and stems, AmSUT1 was localized
      exclusively in phloem cells. Further histological characterization identified
      these cells as companion cells and sieve elements. p-Chloromercuribenzenesulfonic
      acid affected the sugar exudation of cut leaves in such a way that the exudation
      rates of Suc and hexoses decreased, whereas those of raffinose and stachyose
      increased. The data presented indicate that phloem loading of Suc and retrieval
      of Suc in A. meridionalis are at least partly mediated by the activity of AmSUT1
      in addition to symplastic phloem loading.

PMID- 14730069
TI  - Characterization and functional identification of a novel plant 4,5-extradiol
      dioxygenase involved in betalain pigment biosynthesis in Portulaca grandiflora.
AB  - Betalains are pigments that replace anthocyanins in the majority of families of
      the plant order Caryophyllales. Betalamic acid is the common chromophore of
      betalains. The key enzyme of the betalain biosynthetic pathway is an extradiol
      dioxygenase that opens the cyclic ring of dihydroxy-phenylalanine (DOPA) between
      carbons 4 and 5, thus producing an unstable seco-DOPA that rearranges
      nonenzymatically to betalamic acid. A gene for a 4,5-DOPA-dioxygenase has already
      been isolated from the fungus Amanita muscaria, but no homolog was ever found in
      plants. To identify the plant gene, we constructed subtractive libraries between
      different colored phenotypes of isogenic lines of Portulaca grandiflora
      (Portulacaceae) and between different stages of flower bud formation. Using in
      silico analysis of differentially expressed cDNAs, we identified a candidate
      showing strong homology at the level of translated protein with the LigB domain
      present in several bacterial extradiol 4,5-dioxygenases. The gene was expressed
      only in colored flower petals. The function of this gene in the betalain
      biosynthetic pathway was confirmed by biolistic genetic complementation in white
      petals of P. grandiflora genotypes lacking the gene for color formation. This
      gene named DODA is the first characterized member of a novel family of plant
      dioxygenases phylogenetically distinct from Amanita sp. DOPA-dioxygenase.
      Homologs of DODA are present not only in betalain-producing plants but also,
      albeit with some changes near the catalytic site, in other angiosperms and in the
      bryophyte Physcomitrella patens. These homologs are part of a novel conserved
      plant gene family probably involved in aromatic compound metabolism.

PMID- 14730070
TI  - Osmotic effects on the electrical properties of Arabidopsis root hair vacuoles in
      situ.
AB  - To assess the role of the vacuole in responses to hyperosmotic and hypo-osmotic
      stress, the electrical properties of the vacuole were measured in situ. A double
      barrel micropipette was inserted into the vacuole for voltage clamping. A second
      double-barrel micropipette was inserted into the cytoplasm to provide a virtual
      ground that separated the electrical properties of the vacuole from those of the
      plasma membrane. Osmotic stress causes immediate electrical responses at the
      plasma membrane (Lew RR [1996] Plant Physiol 97: 2002-2005) and ion flux changes
      and turgor recovery (Shabala SN, Lew RR [2002] 129: 290-299) in Arabidopsis root
      cells. In situ, the vacuole also responds rapidly to changes in extracellular
      osmotic potential. Hyperosmotic treatment caused a very large increase in the
      ionic conductance of the vacuole. Hypo-osmotic treatment did not affect the
      vacuolar conductance. In either case, the vacuolar electrical potential was
      unchanged. Taken in concert with previous studies of changes at the plasma
      membrane, these results demonstrate a highly coordinated system in which the
      vacuole and plasma membrane are primed to respond immediately to hyperosmotic
      stress before changes in gene expression.

PMID- 14730071
TI  - Environmentally induced plasticity of root hair development in Arabidopsis.
AB  - Postembryonic development of plants is dependent on both intrinsic genetic
      programs and environmental factors. The plasticity of root hair patterning in
      response to environmental signals was investigated in the Columbia-0 wild type
      and 19 Arabidopsis mutants carrying lesions in various parts of the root hair
      developmental pathway by withholding phosphate or iron (Fe) from the nutrient
      medium. In the aging primary root and in laterals of the wild type, the number of
      root hairs increased in response to phosphate and Fe deficiency in a manner
      typical of each growth type. Although an increase in root hair density in 
      phosphorus plants was mainly achieved by the formation of extra hairs over both
      tangential and radial wall of underlying cortical cells, roots of -Fe plants were
      characterized by a high percentage of extra hairs with two tips. Root hair
      patterning and hair length was differentially affected by the presence or absence
      of phosphate and Fe among the genotypes under investigation, pointing to separate
      cascades of gene activation under all three growth conditions. Divergence in root
      hair patterning was most pronounced among mutants with defects in genes that
      affect the first stages of differentiation, suggesting that nutritional signals
      are perceived at an early stage of epidermal cell development. During elongation
      of the root hairs, no differences in the requirement of gene products between the
      growth types were obvious. The role of genes involved in root hair development in
      the aging primary root of Arabidopsis under the various growth conditions is
      discussed.

PMID- 14730072
TI  - The galactose residues of xyloglucan are essential to maintain mechanical
      strength of the primary cell walls in Arabidopsis during growth.
AB  - In land plants, xyloglucans (XyGs) tether cellulose microfibrils into a strong
      but extensible cell wall. The MUR2 and MUR3 genes of Arabidopsis encode XyG
      specific fucosyl and galactosyl transferases, respectively. Mutations of these
      genes give precisely altered XyG structures missing one or both of these
      subtending sugar residues. Tensile strength measurements of etiolated hypocotyls
      revealed that galactosylation rather than fucosylation of the side chains is
      essential for maintenance of wall strength. Symptomatic of this loss of tensile
      strength is an abnormal swelling of the cells at the base of fully grown
      hypocotyls as well as bulging and marked increase in the diameter of the
      epidermal and underlying cortical cells. The presence of subtending galactosyl
      residues markedly enhance the activities of XyG endotransglucosylases and the
      accessibility of XyG to their action, indicating a role for this enzyme activity
      in XyG cleavage and religation in the wall during growth for maintenance of
      tensile strength. Although a shortening of XyGs that normally accompanies cell
      elongation appears to be slightly reduced, galactosylation of the XyGs is not
      strictly required for cell elongation, for lengthening the polymers that occurs
      in the wall upon secretion, or for binding of the XyGs to cellulose.

PMID- 14730073
TI  - Tobacco nectarin V is a flavin-containing berberine bridge enzyme-like protein
      with glucose oxidase activity.
AB  - Ornamental tobacco (Nicotiana langsdorffii X N. sanderae) secretes a limited
      array of proteins (nectarins) into its floral nectar. Careful sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis of tobacco nectar revealed
      that a broad protein band from 61 to 65 kD actually consists of five discrete
      protein bands. N-terminal sequencing and tryptic peptide mass spectrometry
      fingerprint analysis demonstrated that the upper three bands are isoforms of the
      same protein, NEC5 (Nectarin V), whereas the lower two bands, NEC4 (Nectarin IV),
      are related to each other but not to NEC5. Reverse transcription-polymerase chain
      reaction (RT-PCR) based upon N-terminal sequence of NEC5 generated a short cDNA
      that encoded the N terminus of the NEC5 protein. Two rounds of inverse-PCR using
      genomic DNA permitted the isolation of approximately one-half of the coding
      region of the nec5 gene along with 787 nucleotides of the 5'-flanking region.
      This DNA fragment was used as a probe to isolate a near full-length nec5 clone
      from a nectary-derived cDNA library. BLAST analysis identified the nec5 cDNA as a
      berberine bridge enzyme-like protein. Approximately 40% of the cDNA sequence
      corresponded to peptides that were identified by tryptic peptide mass
      spectrometry fingerprint analysis of the NEC5 protein, thereby confirming that
      this cDNA encoded the NEC5 protein. In-gel assays also demonstrated that NEC5
      contains a covalently linked flavin, and it possesses glucose oxidase activity.
      RT-PCR-based expression analyses showed that nec5 expression is limited
      exclusively to the nectary gland during late stages of floral development.

PMID- 14730074
TI  - Towards functional proteomics of membrane protein complexes in Synechocystis sp.
      PCC 6803.
AB  - The composition and dynamics of membrane protein complexes were studied in the
      cyanobacterium Synechocystis sp. PCC 6803 by two-dimensional blue native/SDS-PAGE
      followed by matrix-assisted laser-desorption ionization time of flight mass
      spectrometry. Approximately 20 distinct membrane protein complexes could be
      resolved from photoautotrophically grown wild-type cells. Besides the protein
      complexes involved in linear photosynthetic electron flow and ATP synthesis
      (photosystem [PS] I, PSII, cytochrome b6f, and ATP synthase), four distinct
      complexes containing type I NAD(P)H dehydrogenase (NDH-1) subunits were
      identified, as well as several novel, still uncharacterized protein complexes.
      The dynamics of the protein complexes was studied by culturing the wild type and
      several mutant strains under various growth modes (photoautotrophic, mixotrophic,
      or photoheterotrophic) or in the presence of different concentrations of CO2,
      iron, or salt. The most distinct modulation observed in PSs occurred in iron
      depleted conditions, which induced an accumulation of CP43' protein associated
      with PSI trimers. The NDH-1 complexes, on the other hand, responded readily to
      changes in the CO2 concentration and the growth mode of the cells and represented
      an extremely dynamic group of membrane protein complexes. Our results give the
      first direct evidence, to our knowledge, that the NdhF3, NdhD3, and CupA proteins
      assemble together to form a small low CO2-induced protein complex and further
      demonstrate the presence of a fourth subunit, Sll1735, in this complex. The two
      bigger NDH-1 complexes contained a different set of NDH-1 polypeptides and are
      likely to function in respiratory and cyclic electron transfer. Pulse labeling
      experiments demonstrated the requirement of PSII activity for de novo synthesis
      of the NDH-1 complexes.

PMID- 14730076
TI  - Is each light-harvesting complex protein important for plant fitness?
AB  - Many of the photosynthetic genes are conserved among all higher plants,
      indicating that there is strong selective pressure to maintain the genes of each
      protein. However, mutants of these genes often lack visible growth phenotypes,
      suggesting that they are important only under certain conditions or have
      overlapping functions. To assess the importance of specific genes encoding the
      light-harvesting complex (LHC) proteins for the survival of the plant in the
      natural environment, we have combined two different scientific traditions by
      using an ecological fitness assay on a set of genetically modified Arabidopsis
      plants with differing LHC protein contents. The fitness of all of the LHC
      deficient plants was reduced in some of the growth environments, supporting the
      hypothesis that each of the genes has been conserved because they provide
      ecological flexibility, which is of great adaptive value given the highly
      variable conditions encountered in nature.

PMID- 14730075
TI  - A novel family of transporters mediating the transport of glutathione derivatives
      in plants.
AB  - Uptake and compartmentation of reduced glutathione (GSH), oxidized glutathione
      (GSSG), and glutathione conjugates are important for many functions including
      sulfur transport, resistance against biotic and abiotic stresses, and
      developmental processes. Complementation of a yeast (Saccharomyces cerevisiae)
      mutant (hgt1) deficient in glutathione transport was used to characterize a
      glutathione transporter cDNA (OsGT1) from rice (Oryza sativa). The 2.58-kb full
      length cDNA (AF393848, gi 27497095), which was obtained by screening of a cDNA
      library and 5'-rapid amplification of cDNA ends-polymerase chain reaction,
      contains an open reading frame encoding a 766-amino acid protein. Complementation
      of the hgt1 yeast mutant strain with the OsGT1 cDNA restored growth on a medium
      containing GSH as the sole sulfur source. The strain expressing OsGT1 mediated
      [3H]GSH uptake, and this uptake was significantly competed not only by unlabeled
      GSSG and GS conjugates but also by some amino acids and peptides, suggesting a
      wide substrate specificity. OsGT1 may be involved in the retrieval of GSSG, GS
      conjugates, and nitrogen-containing peptides from the cell wall.

PMID- 14730077
TI  - Auxin from the developing inflorescence is required for the biosynthesis of
      active gibberellins in barley stems.
AB  - Multiple gibberellins (GAs) were quantified in the stems of intact, decapitated,
      and decapitated auxin-treated barley (Hordeum vulgare) plants. Removal of the
      developing inflorescence reduced the endogenous levels of indole-3-acetic acid
      (IAA), GA(1), and GA(3) and increased the level of GA(29) in internodal and nodal
      tissues below the site of excision. Application of IAA to the excised stump
      restored GA levels to normal in almost all cases. The conversion of [(14)C]GA(20)
      to bioactive [(14)C]GA(1) and of [(14)C]GA(5) to bioactive [(14)C]GA(3) was
      reduced by decapitation, and IAA application was able to restore conversion rates
      back to the levels found in intact plants. The amount of mRNA for the principal
      vegetative 3-oxidase (converting GA(20) to GA(1), and GA(5) to GA(3)) was
      decreased in decapitated plants and restored by IAA application. The results
      indicate that the inflorescence of barley is a source of IAA that is transported
      basipetally into the internodes and nodes where bioactive GA(1) and GA(3) are
      biosynthesized. Thus, IAA is required for normal GA biosynthesis in stems, acting
      at multiple steps in the latter part of the pathway.

PMID- 14730078
TI  - Identification of the protein storage vacuole and protein targeting to the
      vacuole in leaf cells of three plant species.
AB  - Protein storage vacuoles (PSVs) are specialized vacuoles devoted to the
      accumulation of large amounts of protein in the storage tissues of plants. In
      this study, we investigated the presence of the storage vacuole and protein
      trafficking to the compartment in cells of tobacco (Nicotiana tabacum), common
      bean (Phaseolus vulgaris), and Arabidopsis leaf tissue. When we expressed
      phaseolin, the major storage protein of common bean, or an epitope-tagged version
      of alpha-tonoplast intrinsic protein (alpha-TIP, a tonoplast aquaporin of PSV),
      in protoplasts derived from leaf tissues, these proteins were targeted to a
      compartment ranging in size from 2 to 5 microm in all three plant species. Most
      Arabidopsis leaf cells have one of these organelles. In contrast, from one to
      five these organelles occurred in bean and tobacco leaf cells. Also, endogenous
      alpha-TIP is localized in a similar compartment in untransformed leaf cells of
      common bean and is colocalized with transiently expressed epitope-tagged alpha
      TIP. In Arabidopsis, phaseolin contained N-glycans modified by Golgi enzymes and
      its traffic was sensitive to brefeldin A. However, trafficking of alpha-TIP was
      insensitive to brefeldin A treatment and was not affected by the dominant
      negative mutant of AtRab1. In addition, a modified alpha-TIP with an insertion of
      an N-glycosylation site has the endoplasmic reticulum-type glycans. Finally, the
      early step of phaseolin traffic, from the endoplasmic reticulum to the Golgi
      complex, required the activity of the small GTPase Sar1p, a key component of coat
      protein complex II-coated vesicles, independent of the presence of the vacuolar
      sorting signal in phaseolin. Based on these results, we propose that the proteins
      we analyzed are targeted to the PSV or equivalent organelle in leaf cells and
      that proteins can be transported to the PSV by two different pathways, the Golgi
      dependent and Golgi-independent pathways, depending on the individual cargo
      proteins.

PMID- 14730079
TI  - Morphogenesis of maize embryos requires ZmPRPL35-1 encoding a plastid ribosomal
      protein.
AB  - In emb (embryo specific) mutants of maize (Zea mays), the two fertilization
      products have opposite fates: Although the endosperm develops normally, the
      embryo shows more or less severe aberrations in its development, resulting in
      nonviable seed. We show here that in mutant emb8516, the development of mutant
      embryos deviates as soon as the transition stage from that of wild-type siblings.
      The basic events of pattern formation take place because mutant embryos display
      an apical-basal polarity and differentiate a protoderm. However, morphogenesis is
      strongly aberrant. Young mutant embryos are characterized by protuberances at
      their suspensor-like extremity, leading eventually to structures of irregular
      shape and variable size. The lack of a scutellum or coleoptile attest to the
      virtual absence of morphogenesis at the embryo proper-like extremity. Molecular
      cloning of the mutation was achieved based on cosegregation between the mutant
      phenotype and the insertion of a MuDR element. The Mu insertion is located in
      gene ZmPRPL35-1, likely coding for protein L35 of the large subunit of plastid
      ribosomes. The isolation of a second allele g2422 and the complementation of
      mutant emb8516 with a genomic clone of ZmPRPL35-1 confirm that a lesion in
      ZmPRPL35-1 causes the emb phenotype. ZmPRPL35-1 is a low-copy gene present at two
      loci on chromosome arms 6L and 9L. The gene is constitutively expressed in all
      major tissues of wild-type maize plants. Lack of expression in emb/emb endosperm
      shows that endosperm development does not require a functional copy of ZmPRPL35-1
      and suggests a link between plastids and embryo-specific signaling events.

PMID- 14730080
TI  - Condensed lignins are synthesized in poplar leaves exposed to ozone.
AB  - Poplar (Populus tremula x alba) trees (clone INRA 717-1-B4) were cultivated for 1
      month in phytotronic chambers with two different levels of ozone (60 and 120 nL
      L(-1)). Foliar activities of shikimate dehydrogenase (EC 1.1.1.25), phenylalanine
      ammonia lyase (EC 4.3.1.5), and cinnamyl alcohol dehydrogenase (CAD, EC
      1.1.1.195) were compared with control levels. In addition, we examined lignin
      content and structure in control and ozone-fumigated leaves. Under ozone
      exposure, CAD activity and CAD RNA levels were found to be rapidly and strongly
      increased whatever the foliar developmental stage. In contrast, shikimate
      dehydrogenase and phenylalanine ammonia lyase activities were increased in old
      and midaged leaves but not in the youngest ones. The increased activities of
      these enzymes involved in the late or early steps of the metabolic pathway
      leading to lignins were associated with a higher Klason lignin content in extract
      free leaves. In addition, stress lignins synthesized in response to ozone
      displayed a distinct structure, relative to constitutive lignins. They were found
      substantially enriched in carbon-carbon interunit bonds and in p
      hydroxyphenylpropane units, which is reminiscent of lignins formed at early
      developmental stages, in compression wood, or in response to fungal elicitor. The
      highest changes in lignification and in enzyme activities were obtained with the
      highest ozone dose (120 nL L(-1)). These results suggest that ozone-induced
      lignins might contribute to the poplar tolerance to ozone because of their
      barrier or antioxidant effect toward reactive oxygen species.

PMID- 14730081
TI  - Hyperaccumulation of cadmium and zinc in Thlaspi caerulescens and Arabidopsis
      halleri at the leaf cellular level.
AB  - Vacuolar compartmentalization or cell wall binding in leaves could play a major
      role in hyperaccumulation of heavy metals. However, little is known about the
      physiology of intracellular cadmium (Cd) sequestration in plants. We investigated
      the role of the leaf cells in allocating metal in hyperaccumulating plants by
      measuring short-term (109)Cd and (65)Zn uptake in mesophyll protoplasts of
      Thlaspi caerulescens "Ganges" and Arabidopsis halleri, both hyperaccumulators of
      zinc (Zn) and Cd, and T. caerulescens "Prayon," accumulating Cd at a lower
      degree. The effects of low temperature, several divalent cations, and pre
      exposure of the plants to metals were investigated. There was no significant
      difference between the Michaelis-Menten kinetic constants of the three plants. It
      indicates that differences in metal uptake cannot be explained by different
      constitutive transport capacities at the leaf protoplast level and that plasma
      and vacuole membranes of mesophyll cells are not responsible for the differences
      observed in heavy metal allocation. This suggests the existence of regulation
      mechanisms before the plasma membrane of leaf mesophyll protoplasts. However, pre
      exposure of the plants to Cd induced an increase in Cd accumulation in
      protoplasts of "Ganges," whereas it decreased Cd accumulation in A. halleri
      protoplasts, indicating that Cd-permeable transport proteins are differentially
      regulated. The experiment with competitors has shown that probably more than one
      single transport system is carrying Cd in parallel into the cell and that in T.
      caerulescens "Prayon," Cd could be transported by a Zn and Ca pathway, whereas in
      "Ganges," Cd could be transported mainly by other pathways.

PMID- 14730082
TI  - Topology of the maize mixed linkage (1->3),(1->4)-beta-d-glucan synthase at the
      Golgi membrane.
AB  - Mixed-linkage (1-->3),(1-->4)-beta-d-glucan is a plant cell wall polysaccharide
      composed of cellotriosyl and cellotetraosyl units, with decreasingly smaller
      amounts of cellopentosyl, cellohexosyl, and higher cellodextrin units, each
      connected by single (1-->3)-beta-linkages. (1-->3),(1-->4)-beta-Glucan is
      synthesized in vitro with isolated maize (Zea mays) Golgi membranes and UDP
      [(14)C]d-glucose. The (1-->3),(1-->4)-beta-glucan synthase is sensitive to
      proteinase K digestion, indicating that part of the catalytic domain is exposed
      to the cytoplasmic face of the Golgi membrane. The detergent [3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonic acid] (CHAPS) also lowers (1-
      >3),(1-->4)-beta-glucan synthase activity. In each instance, the treatments
      selectively inhibit formation of the cellotriosyl units, whereas synthesis of the
      cellotetraosyl units is essentially unaffected. Synthesis of the cellotriosyl
      units is recovered when a CHAPS-soluble factor is permitted to associate with
      Golgi membranes at synthesis-enhancing CHAPS concentrations but lost if the CHAPS
      soluble fraction is replaced by fresh CHAPS buffer. In contrast to other known
      Golgi-associated synthases, (1-->3),(1-->4)-beta-glucan synthase behaves as a
      topologic equivalent of cellulose synthase, where the substrate UDP-glucose is
      consumed at the cytosolic side of the Golgi membrane, and the glucan product is
      extruded through the membrane into the lumen. We propose that a cellulose
      synthase-like core catalytic domain of the (1-->3),(1-->4)-beta-glucan synthase
      synthesizes cellotetraosyl units and higher even-numbered oligomeric units and
      that a separate glycosyl transferase, sensitive to proteinase digestion and
      detergent extraction, associates with it to add the glucosyl residues that
      complete the cellotriosyl and higher odd-numbered units, and this association is
      necessary to drive polymer elongation.

PMID- 14730083
TI  - Localization of an ascorbate-reducible cytochrome b561 in the plant tonoplast.
AB  - As a free radical scavenger, and cofactor, ascorbate (ASC) is a key player in the
      regulation of cellular redox processes. It is involved in responses to biotic and
      abiotic stresses and in the control of enzyme activities and metabolic reactions.
      Cytochromes (Cyts) b561 catalyze ASC-driven trans-membrane electron transport and
      contribute to ASC-mediated redox reactions in subcellular compartments. Putative
      Cyts b561 have been identified in Arabidopsis (ecotype Columbia) on the basis of
      sequence similarity to their mammalian counterparts. However, little is known
      about the function or subcellular localization of this unique class of membrane
      proteins. We have expressed one of the putative Arabidopsis Cyt b561 genes
      (CYBASC1) in yeast and we demonstrate that this protein encodes an ASC-reducible
      b-type Cyt with absorbance characteristics similar to that of other members of
      this family. Several lines of independent evidence demonstrate that CYBASC1 is
      localized at the plant tonoplast (TO). Isoform-specific antibodies against
      CYBASC1 indicate that this protein cosediments with the TO marker on sucrose
      gradients. Moreover, CYBASC1 is strongly enriched in TO-enriched membrane
      fractions, and TO fractions contain an ASC-reducible b-type Cyt with alpha-band
      absorbance maximum near 561 nm. The TO ASC-reducible Cyt has a high specific
      activity, suggesting that it is a major constituent of this membrane. These
      results provide evidence for the presence of trans-membrane redox components in
      this membrane type, and they suggest the coupling of cytoplasmic and vacuolar
      metabolic reactions through ASC-mediated redox activity.

PMID- 14730084
TI  - Arabidopsis type B monogalactosyldiacylglycerol synthase genes are expressed
      during pollen tube growth and induced by phosphate starvation.
AB  - The galactolipids monogalactosyldiacylglycerol (MGDG) and
      digalactosyldiacylglycerol (DGDG) constitute the major glycolipids of the
      thylakoid membranes in chloroplasts. In Arabidopsis, the formation of MGDG is
      catalyzed by a family of three MGDG synthases, which are encoded by two types of
      genes, namely type A (atMGD1) and type B (atMGD2 and atMGD3). Although the roles
      of the type A enzyme have been intensively investigated in several plants, little
      is known about the contribution of type B enzymes to MGDG synthesis in planta.
      From our previous analyses, unique expression profiles of the three MGDG synthase
      genes were revealed in various organs and developmental stages. To characterize
      the expression profiles in more detail, we performed histochemical analysis of
      these genes using beta-glucuronidase (GUS) assays in Arabidopsis. The expression
      of atMGD1::GUS was detected highly in all green tissues, whereas the expression
      of atMGD2::GUS and atMGD3::GUS was observed only in restricted parts, such as
      leaf tips. In addition, intense staining was detected in pollen grains of all
      transformants. We also detected GUS activity in the pollen tubes of atMGD2::GUS
      and atMGD3::GUS transformants grown in wild-type stigmas but not in atMGD1::GUS,
      suggesting that type B MGDG synthases may have roles during pollen germination
      and pollen tube growth. GUS analysis also revealed that expression of atMGD2 and
      atMGD3, but not atMGD1, are strongly induced during phosphate starvation,
      particularly in roots. Because only DGDG accumulates in roots during phosphate
      deprivation, type B MGDG synthases may be acting primarily to supply MGDG as a
      precursor for DGDG synthesis.

PMID- 14730086
TI  - Potential antidepressant activity of sigma ligands.
AB  - Despite many years' studies of antidepressant drugs (ADs), their mechanism of
      action still remains unclear. Recently, it has been postulated that substances
      capable of reducing neurotransmission at the NMDA complex may represent a new
      class of ADs. Since several ADs have a high affinity for sigma receptors, the
      sigma binding site may be a relevant mechanism in antidepressant action.
      Moreover, sigma ligands are able to modulate the activity of the central
      neurotransmitter systems, including noradrenergic, serotonergic, dopaminergic and
      glutamatergic (NMDA) ones, which are seemingly important for the mechanism of
      action of known ADs. The existence of at least two different subtypes of sigma
      receptors, denoted sigma1 and sigma2 is now widely accepted. The selective
      agonists of both sigma receptor subtypes are available at present. In particular,
      a potential antidepressant activity of sigma1 receptor agonists has been
      postulated, since the antidepressive-like actions of these compounds have been
      shown in animal models. This article reviews the findings related to potential
      antidepressant activity of new, selective sigma ligands.

PMID- 14730085
TI  - A transcriptomic and proteomic characterization of the Arabidopsis mitochondrial
      protein import apparatus and its response to mitochondrial dysfunction.
AB  - Mitochondria import hundreds of cytosolically synthesized proteins via the
      mitochondrial protein import apparatus. Expression analysis in various organs of
      19 components of the Arabidopsis mitochondrial protein import apparatus encoded
      by 31 genes showed that although many were present in small multigene families,
      often only one member was prominently expressed. This was supported by comparison
      of real-time reverse transcriptase-polymerase chain reaction and microarray
      experimental data with expressed sequence tag numbers and massive parallel
      signature sequence data. Mass spectrometric analysis of purified mitochondria
      identified 17 import components, their mitochondrial sub-compartment, and
      verified the presence of TIM8, TIM13, TIM17, TIM23, TIM44, TIM50, and METAXIN
      proteins for the first time, to our knowledge. Mass spectrometry-detected
      isoforms correlated with the most abundant gene transcript measured by expression
      data. Treatment of Arabidopsis cell culture with mitochondrial electron transport
      chain inhibitors rotenone and antimycin A resulted in a significant increase in
      transcript levels of import components, with a greater increase observed for the
      minor isoforms. The increase was observed 12 h after treatment, indicating that
      it was likely a secondary response. Microarray analysis of rotenone-treated cells
      indicated the up-regulation of gene sets involved in mitochondrial chaperone
      activity, protein degradation, respiratory chain assembly, and division. The rate
      of protein import into isolated mitochondria from rotenone-treated cells was
      halved, even though rotenone had no direct effect on protein import when added to
      mitochondria isolated from untreated cells. These findings suggest that
      transcription of import component genes is induced when mitochondrial function is
      limited and that minor gene isoforms display a greater response than the
      predominant isoforms.

PMID- 14730087
TI  - Role of metabotropic glutamate receptors in animal models of Parkinson's disease.
AB  - The efficacy of the majority of drugs currently used for treatment of Parkinson's
      disease is insufficient. Moreover, such therapeutics are not devoid of serious
      side effects. Multiple studies on animal models of parkinsonism have shown that
      new class of drugs, acting selectively on metabotropic glutamate receptors
      (mGluRs) might be very promising for the future therapy of Parkinson's disease.
      This review briefly describes changes in glutamatergic transmission in the
      neuronal circuitry of the extrapyramidal system that occur in parkinsonian
      patients, contains background information on structure, function and distribution
      of mGluRs throughout the basal ganglia and concentrates on discussion of the
      results obtained from numerous animal model studies aimed to establish potential
      antiparkinsonian properties of various mGluR ligands. The reviewed literature
      data indicate that among these compounds group I mGluR antagonists and group II
      mGluR agonists might be beneficial to the treatment of parkinsonian akinesia and
      muscle rigidity.

PMID- 14730088
TI  - Influence of acute and chronic 1,2,3,4-tetrahydroisoquinoline administration on
      the expression of proenkephalin mRNA in the rat striatum.
AB  - Animal studies have shown that a depletion of dopamine or blockade of dopamine D2
      receptors in the striatum produces an increase in striatal proenkephalin (PENK)
      mRNA expression and an increase in GABAergic transmission in the globus pallidus.
      Therefore, it has been suggested that an enhanced striatal PENK mRNA expression
      may reflect to some extent an increase in the activity of the GABAergic
      striatopallidal pathway whose overactivity has been suggested to take place in
      the course of Parkinson's disease. Therefore, the aim of the study was to
      investigate the role of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous
      substance suspected of producing parkinsonism in humans, in the regulation of the
      activity of GABAergic striatopallidal pathway in rats. TIQ administered acutely
      at the dose of 100 mg/kg ip increased the PENK mRNA expression in the dorsal part
      of the striatum at two levels I and II (rostral and central striatum,
      respectively). No changes were noticed in the ventral part of the striatum.
      Moreover, TIQ given chronically to rats for 3 weeks did not modify the level of
      PENK mRNA in any examined part of the striatum. The present results show that the
      effect of TIQ on the PENK mRNA expression is different from that described for
      proparkinsonian model neurotoxins (MPTP, 6-OHDA) as well as for typical
      neuroleptics, such as haloperidol.

PMID- 14730089
TI  - Neonatal 5-hydroxytryptamine depletion induces depressive-like behavior in adult
      rats.
AB  - The influence of neonatal serotonergic lesion on adult behavior in locomotor and
      depression models was studied in male Wistar rats. When 3-day-old rats were
      injected intracisternally with 5,7-dihydroxytryptamine (5,7-DHT), a marked
      depletion of brain 5-HT was observed when animals were killed 3 months after the
      treatment. Brain catecholamine content was generally not changed by neurotoxin
      treatment. The behavioral consequence of intracisternal 5,7-DHT administration to
      developing rats consisted in reduction of adult rats' activity in the forced
      swimming test. Both desipramine, and, to the lesser extent, fluoxetine, reversed
      5,7-DHT-induced immobility of animals.

PMID- 14730091
TI  - Anxiolytic-like profile of propofol, a general anesthetic, in the plus-maze test
      in mice.
AB  - The present study was performed to investigate the effect of propofol on anxiety
      using the elevated plus-maze test. Groups of mice received propofol (20, 40, 60
      mg/kg) or diazepam (2 mg/kg), caffeine (30 mg/kg), L-arginine (100 mg/kg), m
      chlorophenylpiperazine (m-CPP, 2.5 mg/kg) and then were placed in an elevated
      plus-maze that was composed of two opposite closed arms and two opposite open
      arms. Propofol (20, 40, 60 mg/kg) and diazepam (2 mg/kg) significantly increased
      the percentage of time spent in the open arms compared to control. Caffeine (30
      mg/kg) and m-CPP (2.5 mg/kg) decreased the percentage of time spent in the open
      arms and these effects were antagonized when propofol (40 mg/kg) was administered
      before the test. L-arginine (100 mg/kg) has also produced anxiogenic effect and
      this effect was not prevented by propofol. All drugs used in this study did not
      significantly change locomotor activity. These results suggest that propofol has
      anxiolytic effect in plus-maze test.

PMID- 14730090
TI  - Effects of gabapentin and antidepressant drug combinations on convulsions and
      memory in mice.
AB  - In epileptic patients, neurobehavioral problems such as cognitive impairment,
      depression, and psychosocial impairments have been described, which may have a
      pathological and/or iatrogenic basis. For this reason additional treatment is
      required, beside antiepileptic drug (AED) therapy, to correct the accompanying
      neurological deficits. However, the rationale behind use of antidepressants along
      with antiepileptics has been questioned due to proconvulsant effects of the
      former. In the present study, the effect of gabapentin (GBP) on seizure score and
      memory is evaluated when it is given alone and in combination with some
      antidepressants, such as sertraline (SERTR) and alprazolam (ALP). Pentetrazole
      (PTZ)-induced convulsion and spontaneous alternation behavior (SAB) models were
      used to study the anticonvulsant effect and effect on memory, respectively.
      Results showed that addition of SERT to GBP or ALP resulted in reduction of
      anticonvulsant efficacy of these drugs. However, the combination of GBP + SERT +
      ALP was superior as far as effect on seizure severity and memory was concerned.

PMID- 14730092
TI  - Neuroprotective effect of NPY on kainate neurotoxicity in the hippocampus.
AB  - Previous studies showed that neuropeptide Y (NPY) inhibited hippocampal
      epileptiform activity and that endogenous NPY might have neuroprotective effects.
      Therefore, in the present study, the effect of NPY microinjected
      intrahippocampally on the kainate-induced lesion and changes in NPY
      immunoreactivity (-IR) were investigated in rat hippocampus. Male Wistar rats,
      chronically cannulated, were unilaterally injected with kainic acid (KA) 2.5
      nmol/1 microl, or additionally with NPY (470 pmol/1 microl) 30 min before or 30
      min after KA injection, into the CA1 or dentate gyrus (DG) area of the
      hippocampus. Seven days later, their brains were taken out and analyzed
      histologically to estimate the lesion extent, and immunohistochemically to assess
      NPY-IR. It was found that KA induced extensive degeneration of CA pyramidal
      neurons and NPY-IR interneurons in the injected hippocampus. Simultaneously, NPY
      immunoreactivity appeared in mossy fibres and some granular cells in the
      contralateral hippocampus. NPY given 30 min after the KA injection into CA1
      region, induced significant diminution of the lesion extent in the CA pyramidal
      layer (diminution by 61%). No significant effect was found when NPY was given 30
      min before KA or when rats were microinjected into the DG area. The obtained
      results indicate neuroprotective action of NPY in some models of the kainate
      induced hippocampal degeneration.

PMID- 14730093
TI  - Effect of L-arginine on memory in rats.
AB  - Effect of intracerebroventricularly (icv) or subcutaneously (sc) injected L
      arginine (L-Arg) on memory was determined using the procedure of passive
      avoidance test. Moreover, locomotor and exploratory activity was determined in
      rats in an open field test. We found that either the peripheral (sc) or icv
      administration of L-Arg significantly prolonged latency time in the passive
      avoidance test. This effect appeared at 20-100-fold higher doses in comparison to
      such effect of arginine vasopressin (AVP) observed in our previous study. This
      memory improving effect was not correlated with the inhibition of locomotor and
      exploratory activity. The effect of the lower icv dose (10 nmoles) of L-Arg was
      blocked by L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor.
      Moreover, the effect of both used doses (10 and 100 nmoles) of L-Arg was also
      blocked by S-methylisothiourea (Mtu), a selective inhibitor of inducible isoform
      of NOS. On the other hand, the effect of higher icv dose of L-Arg (100 nmoles)
      was prevented by 7-nitroindazole (7-NI), an inhibitor of neuronal NOS. We
      conclude that a uniform effect of L-Arg on memory is mediated by different
      isoforms of NOS, mainly by neuronal and inducible NOS.

PMID- 14730094
TI  - Effects of combined treatment with imipramine and metyrapone in the forced
      swimming test in rats. Behavioral and pharmacokinetic studies.
AB  - In the present study, we examined the effects of imipramine (IMI) and metyrapone
      (MET) given alone or in combination of IMI and MET in the forced swimming test in
      rats. We also measured pharmacokinetic parameters: the level of IMI and its
      metabolite, desipramine (DMI), in the rat plasma and brain (1 h after the forced
      swimming test). The present studies indicate that MET (50 mg/kg) reduced
      immobility time. Combined treatment with MET (50 mg/kg) and IMI (5 or 10 mg/kg)
      produced stronger antidepressant-like effect than either of drugs given alone.
      Sulpiride (dopamine D2/3 antagonist), or WAY 100635 (5-HT1A antagonist) but not
      prazosin, (alpha1-adrenergic antagonist), at doses ineffective in the forced
      swimming test, inhibited an antidepressant-like effect induced by co
      administration of IMI with MET. The active behaviors in that test did not reflect
      an increase in general activity, since combined administration of IMI and MET
      failed to alter the locomotor activity of rats, measured in the open field test.
      MET elevated the concentrations of IMI and DMI in plasma, and the total drug
      concentration (IMI + DMI) was doubled by MET. In the brain, MET enhanced the
      concentration of IMI, but decreased that of DMI, consequently, the brain IMI/DMI
      ratio increased twice. The total drug concentration in the brain (IMI + DMI) was
      not changed significantly by MET treatment. The obtained results suggest that
      dopamine D2/3 and 5-HT1A receptors may contribute to the mechanism of synergistic
      action of IMI and MET in the forced swimming test in rats, and that
      pharmacokinetic interaction should not have a substantial impact on the MET
      induced potentiation of IMI effect, observed in vivo. These findings may be of
      particular importance to pharmacotherapy of drug-resistant depression.

PMID- 14730095
TI  - Effect of cyclooxygenase and NO synthase inhibitors administered centrally on
      antinociceptive action of acetaminophen (Part II).
AB  - As it has been demonstrated in a previous study, both cyclooxygenases (COXs) and
      nitric oxide synthases (NOSs) participate in the mechanism of acetaminophen
      (ACETA) action. Results obtained in this study indicate that intrathecal (it) or
      intracerebroventricular (icv) pretreatment with LG-nitro-L-arginine (L-NO-Arg), a
      non-selective inhibitor of NOS activity, as well as with 7-nitroindazole (7-NI),
      a selective nNOS inhibitor, potentiated the antinociceptive activity of
      subceiling doses of ACETA, but were without effect on the action of supramaximal
      doses in Randall-Selitto test. Similar effect of L-NO-Arg and 7-NI it was
      observed in writhing test, whereas L-NO-Arg icv or L-NIL it did not influence the
      action of ACETA in this model. Indomethacin (IND), an inhibitor preferentially
      acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e.
      preferential and selective inhibitor of COX-2, respectively, administered icv
      almost completely blocked the antinociceptive effect of ACETA in Randall-Selitto
      method. On the other hand, pretreatment with NSAIDs it initially increased and
      then attenuated the ACETA antinociception. Yohimbine (YOH), an alpha2-adrenergic
      receptor antagonist, did not modify the antinociceptive action of ACETA
      administered alone. However, YOH decreased the nociceptive threshold increased by
      simultaneously administered IND and ACETA, NIM and ACETA, as well as CECOX and
      ACETA in Randall-Selitto model. In contrast to the peripheral (sc) application,
      IND administered centrally (icv or it) did not modify the ACETA antinociception
      in writhing test. Neither NIM nor CECOX administered sc, it or icv changed the
      ACETA antinociception in this model. Possible mechanisms and sites of
      antinociceptive effects of ACETA are discussed.

PMID- 14730096
TI  - Synthesis, in vitro and in vivo 5-HT1A/5-HT2A serotonin receptor activity of new
      hybrid 1,2,3,4-tetrahydro-gamma-carbolines with 1-(2-methoxyphenyl)piperazine
      moiety.
AB  - A series of 15 new 2-H- and 2-substituted 5-[omega-[4-(2-methoxyphenyl)
      piperazinyl]-alkyl]-1,2,3,4-tetrahydro-gamma-carboline derivatives were prepared,
      and their affinity for 5-HT1A and 5-HT2A serotonin receptors was determined. Most
      of those hybrid compounds were found to bind with high affinity to 5-HT1A sites
      (Ki < 50 nM; 2d, 3a, 3b, 3d, 3e, 4b, 4d, 4e) and moreover two of them (4d, 4e)
      were mixed 5-HT1A/5-HT2A ligands. The results of a lower lip retraction test in
      rats indicated that the 2-acetyl derivative with a dimethylene spacer (2d) had
      features of a postsynaptic 5-HT1A receptor agonist, whereas its analogues with
      longer chains (3d and 4d) behaved like antagonists. Both 5-HT2A receptor ligands
      (4d, 4e) at high doses inhibited the (+/-)-DOI-induced head twitches in mice and
      were classified as weak antagonists of those receptors.

PMID- 14730097
TI  - Nitric oxide- and prostaglandin-mediated cardioprotection by bradykinin in
      myocardial ischemia and reperfusion injury.
AB  - The aim of the present study was to investigate the involvement of nitric oxide
      and prostaglandin pathways in the cardioprotective actions mediated by bradykinin
      via the combined inhibition of angiotensin converting enzyme and aminopeptidase P
      in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h).
      Myocardial infarction was produced by occlusion of the left anterior descending
      coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was
      measured by using the staining agent TTC (2,3,5-triphenyl-tetrazolium chloride).
      Lipid peroxide levels in serum and in heart tissue were estimated
      spectrophotometrically. A lead II ECG was monitored at various intervals
      throughout the experiment. Infarct size expressed as percent of left ventricle
      was found to be 50.5 +/- 3.5 in control animals and was reduced to 19.4 +/- 1.1
      and 15.0 +/- 2.1 with the combined treatment of enalapril or lisinopril and 2
      mercaptoethanol, respectively. There was no significant difference in the infarct
      size of control animals and in the animals treated with HOE140 prior to the
      combined treatment. Infarct size reduction obtained with the combined inhibition
      with enalapril and 2-mercaptoethanol or lisinopril and 2-mercaptoethanol was
      blocked partially but significantly with the prior administration of L-NAME
      (Nomega-nitro-L-arginine methyl ester) or aspirin, suggesting the involvement of
      both nitric oxide and prostaglandin pathways in the cardioprotective actions
      mediated by bradykinin.

PMID- 14730098
TI  - Evaluation of the antiperoxidative effects of melatonin in ammonium acetate
      treated Wistar rats.
AB  - The efficacy of melatonin (MLT) against ammonium acetate-induced neurotoxicity
      was biochemically studied in the experimental rats. The activities of serum
      transaminases and the levels of thiobarbituric acid reactive substances were
      significantly increased in ammonium acetate-treated rats. These levels were
      significantly decreased in MLT and ammonium acetate-treated rats. Further, non
      enzymatic (vitamin C and E) and enzymatic (superoxide dismutase and catalase)
      antioxidants were significantly decreased in ammonium acetate-treated rats and
      were increased in MLT and ammonium acetate-treated rats. These biochemical
      alterations during MLT treatment could be due to its ability to: (i) scavenge a
      variety of radicals and reactive species, (ii) induce antioxidative enzymes which
      reduce steady state levels of reactive species, (iii) inhibit nitric oxide
      synthase which generates nitric oxide and (iv) stabilize cell membranes which
      assists them in reducing oxidative damage and, thus, prevents the oxidative
      stress in rats.

PMID- 14730100
TI  - Effects of classic and newer antidepressants on the oxidation pathways of
      caffeine in rat liver. In vitro study.
AB  - Caffeine undergoes 3-N-demethylation via CYP1A2, as well as 1-N-demethylation, 7
      N-demethylation and 8-hydroxylation, which may involve other CYP isoenzymes. The
      aim of the present study was to investigate the influence of clomipramine,
      desipramine, sertraline, nefazodone and mirtazapine on cytochrome P-450 activity
      measured by caffeine oxidation in rat liver microsomes. The obtained results
      showed that all the investigated antidepressants, with an exception of
      mirtazapine, added in vitro to liver microsomes had an inhibitory effect on
      caffeine metabolism (via competitive or mixed mechanism), though their potency
      towards particular metabolic pathways was different. Dixon analysis of caffeine
      metabolism carried out in the control liver microsomes, in the absence and
      presence of the antidepressant drugs showed that desipramine and clomipramine
      exerted the most potent inhibitory effect on caffeine metabolism. Desipramine
      decreased the rates of 1-N-, 3-N- and 7-N-demethylations, and 8-hydroxylation of
      caffeine (Ki = 23.3, 36.6, 23.3 and 63.3 microM, respectively), the effect on 1-N
      and 7-N-demethylation being the most pronounced. Clomipramine showed distinct
      inibition of 1-N- and 3-N-demethylation and 8-hydroxylation of caffeine, the
      effects on N-demethylations being the most pronounced (Ki = 38.6, 34.8, 45.6
      microM, respectively). Its effect on 7-N-demethylation was rather weak (Ki = 97.8
      microM). Sertraline decreased significantly the rate of 1-N- and 3-N
      demethylation and 8-hydroxylation (Ki = 37.3, 69.3 and 64 microM, respectively),
      while its effect on 7-N-demethylation of caffeine was less pronounced (Ki = 92.1
      microM). Nefazodone displayed clear effect on 3-N- and 7-N-demethylation (Ki =
      68.8 and 66.4 microM, respectively), but was weak in inhibiting 1-N-demethylation
      and 8-hydroxylation of caffeine (Ki = 110 and 186 microM, respectively). In
      contrast to the above-tested antidepressants, mirtazapine did not decrease
      significantly the oxidation rates of 3-N-demethylation or 8-hydroxylation (Ki =
      264 and 455 microM, respectively) and had no effect on other oxidation pathways
      of caffeine. In summary, we have observed intra- and inter-drug differences in
      the inhibitory effects of the antidepressants on the four oxidation pathways of
      caffeine in rat liver microsomes. The tested antidepressants (with an exception
      of mirtazapine) may lead to drug-drug metabolic interactions at a level of a few
      CYP isoforms. The obtained results provide further indirect evidence that apart
      from CYP1A2, other CYP isoforms are also important for the metabolism of
      caffeine.

PMID- 14730099
TI  - Taurine prevents acrylonitrile-induced oxidative stress in rat brain.
AB  - Acrylonitrile (ACN) is a volatile, toxic liquid used as a monomer in the
      manufacture of synthetic rubber, styrene plastics, acrylic fiber and adhesives.
      ACN is a potent neurotoxin and a carcinogen, which produces tumors in rats,
      particularly gliomas of the brain. A role for free radical-mediated lipid
      peroxidation in the toxicity of ACN has been suggested. We examined the ability
      of taurine, an antioxidant amino acid, to attenuate ACN-induced alterations in
      lipid peroxidation, cellular DNA fragmentation, GSH, vitamin C and vitamin E
      levels in blood and brain of rats. Rats were administered with ACN at a
      concentration of 100 ppm in drinking water and sacrificed after 14 and 28 days.
      The level of lipid peroxidation and the enzymatic and non-enzymatic antioxidants
      were assayed. The obtained data were compared with those obtained from ACN rats
      co-treated with taurine for 14 and 28 days. It was observed that taurine
      treatment counteracted the oxidative stress induced by ACN by reducing the levels
      of peroxidation, and enhancing the activities of enzymatic and non-enzymatic
      antioxidants.

PMID- 14730102
TI  - Pharmacokinetics of liposomes designed to carry glucocorticoids.
AB  - Over the past decade, particulate drug formulations have been successfully
      employed to reduce undesired side effects and improve drug biodistribution.
      Despite numerous experimental data, there are relatively few theoretical studies
      regarding the pharmacokinetics of such formulations. A quantitative
      pharmacokinetic description of particulate drug forms requires serious
      adjustments in existing theoretical approaches, due to formulation size. Thus,
      blood vessel permeabilization and the immunological system need to be accounted
      for. In this paper, we present a pharmacokinetic model intended to describe the
      distribution of glucocorticoid (prednisolone phosphate) encapsulated in long
      circulated liposomes and its qualitative analysis. In order to achieve
      qualitative and quantitative agreement with experimental patterns of time
      dependent liposome concentration changes in blood, liver and spleen, the
      existence of two hypothetical liposome populations was assumed. The two
      populations differ in their accumulation capacities, dosage and time constants.
      The first population is accumulated in the liver with a time constant of 50 s(-1)
      and a saturation level of 0.005 micromol/animal, whereas the second with 0.003 s(
      1) and 50 micromol/animal, respectively. Such liposome parameterization results
      from the theoretical model used, however, it may have a physiological foundation.
      If the two opsonin and/or macrophage types that interact with the liposomes are
      assumed to have different characteristics, then the pharmacokinetic data obtained
      experimentally in an animal model can be described correctly.

PMID- 14730101
TI  - Influence of classic and atypical neuroleptics on caffeine oxidation in rat liver
      microsomes.
AB  - Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation)
      in humans and rats. Moreover, CYP3A seems to be essential for its metabolism (8
      hydroxylation). In the case of 1-N- and, in particular, 7-N-demethylation of
      caffeine, apart from CYP1A2, other CYP isoenzymes play a considerable role,
      probably CYP2B and/or CYP2E1. The aim of the present study was to investigate the
      influence of two classic neuroleptics (promazine and haloperidol) and two
      atypical ones (risperidone and sertindole) on cytochrome P-450 activity measured
      by caffeine oxidation in rat liver microsomes. The obtained results showed that
      promazine, a phenothiazine neuroleptic with the simplest chemical structure,
      significantly inhibited 1-N- and 3-N-demethylation and 8-hydroxylation of
      caffeine via competitive or mixed mechanism (Ki = 21.8, 25.4 and 58.2 microM,
      respectively). This indicates inhibition by promazine of CYP1A2 (inhibition of 3
      N- and 1-N-demethylation), and possibly CYP3A2 (inhibition of 8-hydroxylation),
      but not of other CYP isoenzymes involved in 7-N-demethylation of caffeine (e.g.
      CYP2B2 and/or CYP2E1). In contrast to promazine, haloperidol had no effect on the
      oxidation reactions of caffeine in the applied in vitro metabolic model. The
      potency of inhibition of caffeine oxidation by risperidone and sertindole
      resembled rather haloperidol than promazine. Risperidone appeared to be a very
      weak inhibitor of 3-N-demethylation and 8-hydroxylation (Ki = 202.5 microM) and
      had no effect on 1-N- and 7-N-demethylation of caffeine. Sertindole was a very
      poor inhibitor of 1-N- and 7-N-demethylations and 8-hydroxylation pathways of the
      marker substance (Ki = 132.1, 434.1 and 173.3 microM, respectively); even the
      observed in vitro inhibition of 3-N-demethylation of caffeine by sertindole (Ki =
      68.9 microM) cannot be of practical significance in vivo, considering extremely
      low pharmacological and therapeutic doses of the neuroleptic. In summary, among
      the investigated neuroleptics, only promazine showed significant inhibitory
      activity towards caffeine metabolism in vitro (inhibition of CYP1A2 and possibly
      CYP3A), which may be of pharmacological and clinical importance in vivo. In
      contrast to promazine, haloperidol and the investigated atypical neuroleptics had
      no or very weak effect on caffeine oxidation in vitro,of no in vivo significance.
      Considering the results of the present and previous studies, it seems highly
      likely that promazine may cause pharmacokinetic interactions, while atypical
      neuroleptics seem to be safe in this respect. Moreover, the observed reaction
      dependent effects of promazine and sertindole provide indirect evidence that
      CYP1A2 is not the only isoenzyme important for the metabolism of caffeine, which
      requires further pharmacological and clinical consideration.

PMID- 14730103
TI  - Effect of neutral endopeptidase inhibition on vascular response induced by
      exogenous angiotensin I in the isolated rat lung.
AB  - It is suggested that vasoconstriction mediated by angiotensin II cleaved from
      angiotensin I by angiotensin converting enzyme (ACE) is counterbalanced by
      concomitant formation of vasodilator angiotensin (1-7) by neutral endopeptidase
      (NEP). Here, we tested this hypothesis using as a bioassay the isolated rat lung
      perfused with Krebs-Henseleit (KH) solution and ventilated with negative
      pressures. Addition of angiotensin I (100 nM) into the isolated lung resulted in
      an immediate increase in pulmonary arterial pressure (Delta PAP) which was not
      accompanied by a significant change in respiratory lung function or weight of the
      lung. The Delta PAP response induced by angiotensin I was abolished by an
      inhibitor of ACE, perindoprilate (1 microM), or by angiotensin type 1 receptor
      antagonist (losartan, 1 microM) but not by angiotensin type 2 receptor antagonist
      (PD 123.319, 10 microM) suggesting the involvement of ACE and AT1 (but not AT2)
      receptors in this response. On the other hand, antagonist of bradykinin receptor
      B2 (icatibant, 100 nM) or an inhibitor of neutral endopeptidase, thiorphan (1
      microM and 10 microM) did not modify DeltaPAP response induced by angiotensin I.
      In summary, in the isolated rat lung perfused with KH solution, ACE has a
      dominant role in the pulmonary conversion of angiotensin I to angiotensin II,
      while NEP-derived angiotensin 1-7 does not seem to constitute a major
      counterbalancing mechanism in the pulmonary vasoconstriction induced by
      endogenously formed angiotensin II.

PMID- 14730104
TI  - Influence of carnosine on the cardiotoxicity of doxorubicin in rabbits.
AB  - The aim of this study was to establish the effect of naturally occurring
      antioxidant carnosine (CAR) on the doxorubicin (DOX)-induced cardiotoxicity in a
      rabbit model. For this purpose, we evaluated the influence of DOX administration
      alone and in a combined therapy with CAR on the hemodynamic parameters and on the
      degree of cardiac muscle cell alterations in rabbits. Thirty one chinchilla
      rabbits were divided into four groups. One group of rabbits was injected iv with
      DOX at a dose of 2 mg kg(-1) weekly for 7 weeks to induce congestive heart
      failure. Another group of rabbits received the same doses of DOX simultaneously
      with CAR at a dose of 100 mg kg(-1) po daily for 9 weeks. Administration of CAR
      started 1 week prior to the first dose of DOX and ended one week after the
      administration of the last dose of DOX. The control groups of animals received
      0.9% NaCl and CAR alone. The following hemodynamic parameters were estimated:
      heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), stroke index
      (SI) and total peripheral resistance (TPR). Registration of the hemodynamic
      parameters in rabbits was performed by Doppler method (Hugo Sachs Elektronik
      Haemodyn). CAR normalized the values of MAP in rabbits receiving DOX and
      increased the values of CI and SI. The influence of CAR on TPR was not
      statistically significant, but there was a decreasing tendency. The degree of
      cardiac muscle cell alterations was examined by light microscopy using Mean Total
      Score (MTS) technique. The histopathological studies revealed smaller damage of
      cardiac muscle in rabbits which received DOX with CAR in comparison to animals
      receiving DOX alone. CAR seems to be cardioprotective during DOX administration.

PMID- 14730105
TI  - Effects of Bulgarian red and white wines on primary hemostasis and experimental
      thrombosis in rats.
AB  - A number of epidemiological studies have demonstrated that moderate red wine
      consumption significantly decreases the risk of ischemic heart disease. Our
      earlier studies provide evidence that Italian red wine modulates primary
      hemostasis and prevents experimental venous thrombosis in rats, independently of
      its alcohol content, by a nitric oxide (NO)-mediated mechanism. In the present
      study, we have tested whether Bulgarian red and white wines can influence
      thrombotic process and primary hemostasis in rats. NO and PGI2 were evaluated as
      possible mediators of these effects. We have found that red wine treatment (for
      10 days) induced a marked prolongation of bleeding time, decrease in platelet
      adhesion to fibrillar collagen, reduction in venous thrombus weight and
      shortening of occlusion time in arterial thrombosis model. The fall in venous
      thrombus weight was also observed after white wine supplementation. Red wine
      affects hemostasis and venous thrombosis after its iv injection 15 min before
      experiment. These effects were prevented by NO inhibitor (L-NAME) and PGI2
      inhibitor (indomethacin). Our results demonstrate the ability of Bulgarian wines
      to modulate primary hemostasis and prevent venous and arterial thrombosis in rat.

PMID- 14730106
TI  - Assessment of efficacy of quercetin-5'-sulfonic acid sodium salt in the treatment
      of acute chromium poisoning: experimental studies.
AB  - Hexavalent chromium compounds exhibit higher toxicity than its trivalent
      compounds since chromium ions in the +6 oxidation state easily cross biological
      membranes. It has recently been proposed that substances reducing chromium ions
      from the +6 to the less toxic +3 oxidation state can be beneficial in management
      of acute chromium poisoning. In vitro studies also demonstrated quercetin-5 '
      sulfonic acid sodium salt (NaQSA) to reduce chromium ions from the +6 to the +3
      oxidation state. The aim of the study was to determine efficacy of NaQSA in
      treatment of acute poisoning with a hexavalent chromium compound. The experiment
      was carried out on male and female Wistar rats which were divided into 4
      experimental (A,B,C,D) and control (K) groups. All animals received
      intragastrically a single CrO3 dose equal to its LD50. Thirty minutes after
      administration of CrO3, NaQSA was administered intragastrically at a dose of 50
      mg/kg (group A) and 100 mg/kg (group B). In groups C and D, NaQSA was
      administered ip 2 h after administration of CrO3 and then twice a day for 4 days
      at doses of 50 mg/kg (group C) and 100 mg/kg (group D). Only intragastric
      administration of NaQSA at a dose of 100 mg/kg decreased mortality in acute
      poisoning with CrO3. In groups B and D, aminotransferase activity was
      statistically significantly dropping from day 7 of the experiment in comparison
      with the group K, which indicates lesser damage to the liver in animals treated
      with NaQSA. Bilirubin concentrations in groups B and D were also much lower than
      in the group K, but the difference between average bilirubin levels in these
      groups and the K was not statistically significant. The results of the study
      suggest the usefulness of NaQSA in the treatment of poisoning with hexavalent
      chromium compounds.

PMID- 14730107
TI  - Effect of macrolide antibiotics on nitric oxide synthase and xanthine oxidase
      activities, and malondialdehyde level in erythrocyte of the guinea pigs with
      experimental otitis media with effusion.
AB  - Although the long-term administrations of macrolide antibiotics are effective for
      diffuse panbronchiolitis, otitis media with effusion (OME), and some other
      diseases, their mechanism of action has not been fully understood. In order to
      elucidate the mechanisms of possible effects of macrolide antibiotics on
      activities of erythrocyte nitric oxide synthase (NOS), xanthine oxidase (XO), and
      malondialdehyde (MDA) levels in experimental OME, we aimed to evaluate the effect
      of macrolide antibiotics (erythromycin, azithromycin, roxithromycin, and
      clarithromycin) using an experimental guinea pig otitis media model. Erythrocyte
      NOS, XO activities, and MDA level were measured in all groups. Erythrocyte NOS
      activities were significantly higher in erythromycin-, azithromycin-,
      roxithromycin-, and clarithromycin-treated groups than in the experimental group.
      Erythrocyte XO activities were significantly lower in erythromycin-, azithromycin
      , roxithromycin-, and clarithromycin-treated groups than in the control group.
      However, erythrocyte XO activities in experimental group were significantly
      higher than those of control group. Erythrocyte MDA levels were significantly
      lower in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated
      groups than those of the experimental group. The MDA levels in erythromycin- and
      roxithromycin-treated groups were significantly higher than those of azithromycin
      treated group. The MDA levels in azithromycin-treated group were significantly
      lower than those of roxithromycin-treated group. In conclusion, the present study
      shows that the macrolide antibiotics (erythromycin, azithromycin, roxithromycin,
      and clarithromycin) increase NOS activity, decrease XO activity and MDA level,
      which is an important indicator of oxidative stress.

PMID- 14730108
TI  - Synthesis of some new 2,5-disubstituted 1,3,4-thiadiazoles containing isomeric
      pyridyl as potent antimicrobial agents.
AB  - Several new 2,5-disubstituted derivatives of 1,3,4-thiadiazoles containing
      isomeric pyridyl were obtained from cyclization of corresponding
      thiosemicarbazides under acidic conditions. The newly synthesized compounds were
      characterized using different methods of spectroscopy such as IR, 1H-NMR, 13C
      NMR, MS and elemental analysis. The minimal inhibitory concentration (MIC)
      results of screening of some of the synthesized compounds were also reported.
      Most of the synthesized compounds have been found to be active against both Gram
      positive and Gram-negative bacteria at less than 3.6 mg/ml. The compound (10b) is
      most active against all seventeen used gram-positive and gram-negative bacteria.

PMID- 14730109
TI  - Involvement of CRF but not NPY in the anxiety regulation via NMDA receptors.
AB  - The study attempts to evaluate whether neuropeptide Y (NPY) and corticotropin
      releasing factor (CRF) are involved in anxiogenic and anxiolytic reactions
      induced by NMDA receptor ligands. The animals were given MK-801 (1 mg/kg, ip), a
      non-competitive NMDA-receptor antagonist, which acts as anxiolytic agent, or NMDA
      (15 mg/kg, ip), which has an anxiogenic effect. The anxiogenic or anxiolytic
      actions of these compounds were evaluated in the plus-maze test. The animals,
      which were given MK-801, were administered BIBO 3304 (130 ng/0.5 microl/site)
      intraamygdalarly and the animals which were given NMDA were administered alpha
      helical CRF (500 ng/0.5 microl/site). BIBO 3304 did not attenuate MK-801-induced
      anxiolysis and alpha-helical CRF abolished NMDA-induced anxiogenesis. Our results
      show that anxiogenic effect of NMDA is mediated via CRF1 receptors and anxiolytic
      action of MK-801 is not dependent on Y1 receptors.

PMID- 14730110
TI  - Blocking impact of clozapine on cocaine locomotor and sensitizing effects in
      rats.
AB  - In the present study, we attempted to determine the effects of an atypical
      antipsychotic drug clozapine on the locomotor activation as well as sensitization
      to cocaine in male Wistar rats. When given acutely to rats, cocaine (10 mg/kg,
      ip) increased 4-fold the animals' locomotor activity. Repeated administration (1
      5 days) of cocaine (10 mg/kg, ip) to rats significantly enhanced on day 10 the
      locomotor activation induced by its challenge dose given after 5-day withdrawal
      (sensitization). When given in combination with acute cocaine, clozapine (10
      mg/kg, but not 2.5-5 mg/kg) attenuated the locomotor effects of the
      psychostimulant. In animals pretreated with clozapine (5-10 mg/kg, but not 2.5
      mg/kg) before each of the 5 daily cocaine injections, a significant dose
      dependent reduction of the locomotor response of animals to the challenge dose of
      cocaine (10 mg/kg) was observed on day 10. A decrease in that response was also
      found in animals treated repeatedly with cocaine (days 1-5) and challenged with
      the psychostimulant combined with clozapine (10 mg/kg, but not 2.5-5 mg/kg) on
      day 10. The obtained results indicate the ability of clozapine to reduce both
      acute and sensitizing locomotor responses to cocaine. These findings seem to be
      in line with recent clinical reports showing that clozapine may be useful in the
      treatment of cocaine abuse, even in schizophrenic patients.

PMID- 14730111
TI  - Inhibitory effect of some neuroactive steroids on cocaine-induced kindling in
      mice.
AB  - Some neuroactive steroids which positively modulate GABAA receptor activity
      suppress cocaine-induced kindling but a possible involvement of other
      neurochemical mechanism in their antiepileptogenic effect remains to be
      elucidated. To this end, in the present study, we evaluated effects of
      allopregnanolone, a positive modulator of the GABAA receptor; its isomer without
      GABAergic activity--isopregnanolone and a negative-modulator of GABAergic
      transmission--dehydroepiandrosterone sulfate on cocaine-induced kindling in mice.
      Animals were pretreated daily with either vehicle or neuroactive steroid and then
      given cocaine (45 mg/kg) for 12 days. After a 14-day washout period in which
      drugs were not administered, the mice were challenged with the same 45 mg/kg dose
      of cocaine. Isopregnanolone (5 mg/kg) and dehydroepiandrosterone sulfate (20
      mg/kg) administered daily with cocaine decreased number of mice exhibiting
      seizures. Allopregnanolone (5 mg/kg) also showed strong tendency to suppress
      cocaine kindling, however, its effect did not reach statistical significance.
      None of the neuroactive steroids had effect on acute cocaine (75 mg/kg ip)
      induced clonic seizures. Further biochemical study showed that the veratridine-
      but not K+ -stimulated release of D-[3H]-aspartate in hippocampal slices was
      higher in cocaine-kindled mice than in the control group. Isopregnanolone (100
      microM) significantly attenuated the veratridine-induced D-[3H]-aspartate release
      in hippocampi of cocaine-kindled group. These data indicate that positive
      modulation of the GABAA receptors is not a critical feature of neuroactive
      steroids that would determine their ability to prevent the cocaine-induced
      kindling.

PMID- 14730112
TI  - Effect of tamoxifen on bone mineral density and blood lipids in ovariectomized
      rats.
AB  - Tamoxifen is widely used in breast cancer therapy and in the treatment of all
      stages of breast cancer including chemoprevention in women at high risk of the
      disease. The most important aspect of tamoxifen therapy concerns its influence on
      bone tissue and lipid metabolism. The aim of the study was to evaluate the effect
      of tamoxifen on bone metabolism and blood cholesterol levels in ovariectomized
      rats. The study was performed on Wistar rats treated with tamoxifen at 2 and 4
      mg/kg/24 h. Total serum cholesterol and low density cholesterol were
      significantly increased in ovariectomized rats (3.24 mmol/l and 2.06 mmol/l) in
      comparison with sham operated control (2.68 mmol/l and 1.44 mmol/l) (p < 0.05).
      Total serum cholesterol and low density cholesterol in tamoxifen-treated rats
      were significantly decreased in comparision with the values in both sham-operated
      and ovariectomized control. Bone mineral content (BMC) and bone mineral density
      (BMD) of femurs of ovariectomized rats (0.32 g and 0.081 g/cm2) decreased
      significantly compared to sham-operated controls (0.42 g and 0.098 g/cm2) (p <
      0.05). Tamoxifen prevented the bone mass reduction induced by ovariectomy. The
      treatment with tamoxifen at doses of 2 mg/kg/24 h and 4 mg/kg/24 h significantly
      increased BMC and BMD in comparison with ovariectomized control. The results
      suggest a beneficial influence of tamoxifen on bone tissue and lipid metabolism.

PMID- 14730113
TI  - Effect of zinc supplementation on antidepressant therapy in unipolar depression:
      a preliminary placebo-controlled study.
AB  - A growing body of evidence implicates a derangement of zinc homeostasis in mood
      disorders. In general, unipolar depression is connected with low blood zinc
      levels that are increased by effective antidepressant therapy. A placebo
      controlled, double blind pilot study of zinc supplementation in antidepressant
      therapy was conducted in patients who fulfilled DSM IV criteria for major
      (unipolar) depression. Patients received zinc supplementation (6 patients; 25 mg
      of Zn2+ once daily) or placebo (8 patients) and were treated with standard
      antidepressant therapy (tricyclic antidepressants, selective serotonin reuptake
      inhibitors). Hamilton Depression Rating Scale (HDRS) and Beck Depression
      Inventory (BDI) were used to assess efficacy of antidepressant therapy, and
      patients' status was evaluated before the treatment and 2, 6 and 12 weeks after
      its commencement. Antidepressant treatment significantly reduced HDRS scores by
      the 2nd week of treatment in both groups, and lowered BDI scores at the 6th week
      in zinc-treated group. Zinc supplementation significantly reduced scores in both
      measures after 6- and 12-week supplementation when compared with placebo
      treatment. This preliminary study is the first demonstration of the benefit of
      zinc supplementation in antidepressant therapy. The mechanism(s) may be related
      to modulation of glutamatergic or immune systems by zinc ion.

PMID- 14730114
TI  - Sigma1 receptor antagonists attenuate antidepressant-like effect induced by co
      administration of 1,3 di-o-tolylguanidine (DTG) and memantine in the forced
      swimming test in rats.
AB  - The obtained results show that DTG, the sigma1/sigma2 receptor agonist, exerts a
      synergistic effect with memantine, an uncompetitive NMDA receptor antagonist, in
      the forced swimming test in rats, and that progesterone and BD 1047, the sigma1
      receptor antagonists, counteract this effect. The results suggest that the sigma1
      receptor subtype may contribute to the behavioral response induced by combined
      administration of DTG and memantine in Porsolt's test in rats.

PMID- 14730115
TI  - Opposite effects of clozapine and sulpiride on the lipopolysaccharide-induced
      inhibition of the GR-mediated gene transcription in fibroblast cells.
AB  - Previously, we have found that some antipsychotic drugs are able to inhibit
      glucocorticoid receptor (GR)-mediated gene transcription. Since these drugs are
      known not only to inhibit hypothalamic-pituitary-adrenal (HPA) axis activity, but
      also to modulate the immunological system, the aim of the present study was to
      compare the effect of sulpiride and clozapine on GR function under basal culture
      conditions and during activation by lipopolysaccharide (LPS). The effect of
      clozapine and sulpiride alone and with LPS, the immune system activator, on
      glucocorticoid-mediated gene transcription was investigated in fibroblast cells,
      stably transfected with a mouse mammary tumor virus--chloramphenicol
      acetyltransferase plasmid (LMCAT cells). Treatment of the cells with clozapine (3
      10 microM) for 2 days significantly and in concentration-dependent manner
      decreased the chloramphenicol acetyltransferase (CAT) activity, while sulpiride
      (1, 3, 5 and 10 microM) was without any effect. LPS (1 microg/ml) given alone
      inhibited the corticosterone-induced gene transcription by ca. 35%. Clozapine (3,
      5 and 10 microM) inhibited the effect of LPS (1 microM), while sulpiride, which
      alone had no effect on GR function, enhanced LPS (1 microM) action. The obtained
      results indicate that inhibition of GR-mediated gene transcription by LPS and
      clozapine can be a mechanism by which these compounds blocked some effects
      induced by glucocorticoids. Opposite effect of clozapine and sulpiride on LPS
      action may result from their distinct effect on activity of some kinases involved
      in regulation of GR transcriptional function and may determine their utility in
      the treatment of schizophrenia with or without immune system activation.

PMID- 14730116
TI  - Early exposure to hypertonic solution strongly intensifies the effects of K+
      channel opener, rilmakalim, in guinea pig ventricular myocytes.
AB  - We report here that early exposure of guinea pig ventricular myocytes to
      hypertonic solution (approximately 400 mOsm compared to 280 mOsm in isotonic
      solution) increased the potency of rilmakalim to evoke ATP-sensitive K+ current
      10 times (pD2 = 7.44 +/- 0.11 compared to pD2 = 6.49 +/- 0.18 in isotonic
      solution) without changing Emax, and observed effect was completely reversed by
      glibenclamide at 1 microM.

PMID- 14730117
TI  - Diagnosis of early chronic pancreatitis by endoscopic ultrasound. Are we there
      yet?
AB  - The diagnosis of chronic pancreatitis at an early stage is a clinical challenge.
      A major limitation is the inability of clinicians to obtain a tissue or
      histological sample to confirm the clinical diagnosis. Currently available
      imaging modalities have limited sensitivity or specificity for diagnosing early
      chronic pancreatitis. Endoscopic ultrasonography (EUS), introduced in the early
      1980's, was first developed to image the pancreas. It overcame many of the
      limitations (abdominal gas and fat) of transabdominal ultrasonography when
      evaluating patients for possible pancreatic diseases. To date, EUS represents the
      most promising imaging modality for diagnosing chronic pancreatitis. Contrary to
      endoscopic retrograde pancreatography (ERCP), EUS has a very low risk of
      complications and can detect abnormalities suggestive of chronic pancreatitis in
      the pancreatic parenchyma and ductal system which are not visible on any other
      imaging modality. The minimal changes in echotexture are difficult to interpret
      because there is no reliable gold standard confirmatory test. There is now some
      evidence in the literature suggesting that these early changes detected by EUS
      correlate with the histological changes of chronic pancreatitis and may predict
      progression to more advanced disease. The EUS diagnosis of chronic pancreatitis
      relies on quantitative (more than qualitative) parenchymal and ductal criteria
      found during evaluation of the pancreas. It is generally accepted that, in the
      absence of any criteria, chronic pancreatitis is unlikely, whereas in the
      presence of 5 or more criteria (out of 9-11) chronic pancreatitis is likely
      although ERCP and pancreatic function tests may still be normal. The diagnostic
      significance of patients with fewer (1-4) criteria found on EUS is currently
      unclear, particularly when other diagnostic tests such as ERCP and function
      testing are normal. In these cases, there is a potential for "over-diagnosis" of
      chronic pancreatitis, since the EUS changes cannot be confirmed by other
      modalities. How can we better understand the implications of EUS detected changes
      when other tests are normal?

PMID- 14730118
TI  - Pancreatic pseudocysts in the 21st century. Part I: classification,
      pathophysiology, anatomic considerations and treatment.

PMID- 14730119
TI  - The value of a pancreatogram in chronic pancreatitis diagnosed by endoscopic
      retrograde cholangiopancreatography.
AB  - CONTEXT: The presence, course and shape of the accessory pancreatic duct have not
      been previously studied in patients with chronic pancreatitis. OBJECTIVES: The
      accessory pancreatic duct exhibits several appearances on pancreatography. It was
      examined using dye-injection endoscopic retrograde cholangiopancreatography, and
      the duct course and shape were studied in patients having chronic pancreatitis
      and were compared to patients with normal pancreatogram. DESIGN: A prospective
      comparative study was carried out. PATIENTS: One hundred and 57 consecutive
      patients (79 males and 78 females) who underwent endoscopic retrograde
      cholangiopancreatography for suspicion of pancreatobiliary disease. SETTING:
      Forty-eight patients were diagnosed as having chronic pancreatitis using
      endoscopic retrograde cholangiopancreatography (28 alcoholic, 4 metabolic, and 16
      idiopathic) and 109 patients had a normal pancreatogram. MAIN OUTCOME MEASURES:
      The insertion type of the accessory pancreatic duct to the main pancreatic duct
      was determined and the terminal portion of the accessory pancreatic duct was
      described in both groups. RESULTS: In patients with chronic pancreatitis, the
      insertion of the accessory pancreatic duct of short type prevailed; 31 patients
      (64.6%), independently of the degree of intensity of chronic pancreatitis.
      However, in patients with a normal pancreatogram, the intermediate and long type
      prevailed, 46 (42.2%) and 41 (37.6%) patients, respectively. In patients with a
      normal pancreatogram Stick type termination occurred in 66 patients (60.0%), and
      in patients having chronic pancreatitis, the Cudgel type was present in 34
      patients (70.8%) which was statistically significant. CONCLUSION: The accessory
      pancreatic duct should be analyzed when we carry out the cholangiopancreatography
      because the patients with short type insertion have a higher risk of developing
      chronic pancreatitis.

PMID- 14730120
TI  - The agreement between measured and predicted resting energy expenditure in
      patients with pancreatic cancer: a pilot study.
AB  - OBJECTIVE: To compare measured resting energy expenditure to resting energy
      expenditure predicted from eight published prediction equations in a sample of
      patients with pancreatic cancer. DESIGN: Cross-sectional study. SETTING:
      Ambulatory patients of a tertiary private hospital. PARTICIPANTS: Eight patients
      with pancreatic cancer (5 males, 3 females; age: 62.0+/- 5.2 years; BMI: 24.4+/-
      3.2 kg/m2; weight loss: 12.1+/- 6.0%; mean+/- SD). METHODS: Resting energy
      expenditure was measured using indirect calorimetry and predicted from eight
      published prediction methods (Harris-Benedict with no injury factor, Harris
      Benedict with 1.3 injury factor, Schofield, Owen, Mifflin, Cunningham, and Wang
      equations and the 20 kcal/kg ratio). Body composition was assessed by deuterium
      oxide dilution technique. Statistical analysis was performed by using the method
      of Bland and Altman, and the Student's t-test. RESULTS: The Harris-Benedict
      equations with an injury factor of 1.3 resulted in a significantly higher mean
      predicted resting energy expenditure compared to measured resting energy
      expenditure, while there was no significant difference between mean measured and
      predicted resting energy expenditure and the other 7 methods. At an individual
      level, the limits of agreement are wide for all equations. The best combination
      of low bias and narrowest limits of agreement was observed in the prediction of
      resting energy expenditure from the Wang equation (based on fat free mass) and
      the Harris-Benedict equation (based on weight and height). CONCLUSION: At a group
      level, there is agreement between mean measured and predicted resting energy
      expenditure with the exception of the Harris-Benedict equation with an injury
      factor of 1.3. The results of this pilot study suggest that, for an individual,
      the limits of agreement are wide, and clinically important differences in resting
      energy expenditure would be obtained. Clinicians need to be aware of the
      limitations of the use of resting energy expenditure prediction equations for
      individuals.

PMID- 14730121
TI  - A case of cannabis-induced pancreatitis.
AB  - CONTEXT: There are no previous reports of acute pancreatitis associated with
      cannabis use in the general population. Drugs of all types are related to the
      aetiology of pancreatitis in approximately 1.4-2.0% of cases. CASE REPORT: We
      report the case of a 29 year old man who presented with acute pancreatitis after
      a period of heavy cannabis smoking. Other causes of the disease were ruled out.
      The pancreatitis resolved itself after the cannabis was stopped and this was
      confirmed by urinary cannabinoid metabolite monitoring in the community.
      CONCLUSION: To our knowledge this is the first description of a case of cannabis
      induced pancreatitis. However, the link is difficult to establish and further
      evidence is required to prove the association.

PMID- 14730122
TI  - Carbofuran-induced acute pancreatitis.
AB  - CONTEXT: Carbamate insecticides are widely used in commercial agriculture and
      home gardening. A serious side effect of organophosphate and carbamate
      intoxication is the development of acute pancreatitis. CASE REPORT: A 36-year-old
      Caucasian woman was admitted to our hospital with cholinergic crisis and
      pancreatitis soon after the ingestion of a carbamate insecticide (carbofuran). An
      abdominal CT scan disclosed pancreatic necrosis with intrapancreatic fluid
      collection, consistent with the development of a pancreatic pseudocyst in a
      subsequent CT scan. No predisposing factor for pancreatitis was evident.
      Pseudocholinesterase levels returned to normal 7 days later and the patient was
      discharged in good physical condition one month after admission. DISCUSSION:
      Although acute pancreatitis is not infrequent after organophosphate intoxication,
      it is quite rare after carbamate ingestion and has not been previously reported
      after carbofuran intoxication.

PMID- 14730123
TI  - Magnetic resonance imaging of acute pancreatitis: the pancreatogram.
AB  - CONTEXT: Acute pancreatitis has been reported in many cases after therapeutic
      ERCP. CASE REPORT: We report the case of a 65 year man old who, after ERCP,
      manifested biologically acute pancreatitis. The patient was observed using
      dynamic MR pancreatography with secretin administration before and after the
      ERCP. The dynamic MR pancreatography prominently displays a radiological sign of
      early chronic pancreatitis: the pancreatogram. CONCLUSION: Our case demonstrates
      a new sign of biologically acute pancreatitis in dynamic MR pancreatography: the
      pancreatogram.

PMID- 14730124
TI  - Hydatid disease of the pancreas.

PMID- 14730125
TI  - Intraductal papillary-mucinous tumor of the pancreas: the clinical research
      continues.

PMID- 14730126
TI  - Amino acid composition of soybean protein increased postprandial carbohydrate
      oxidation in diabetic mice.
AB  - The effects of an amino acid mixture simulating dietary soybean protein on the
      postprandial energy metabolism was investigated using type II diabetic mice. KK
      A(y) strain mice were fed restrictive isoenergetic and isonitrogenous diets (35%
      of energy as protein and 5% as fat) based on either casein, soybean protein
      isolate hydrolysate (SPI-H), SPI-HET (ethanol unsoluble fraction of SPI-H), SPI
      AA and casein-AA (amino acid mixtures simulating SPI-H and casein). To measure
      dietary carbohydrate oxidation, the animals were fed a diet containing (13)C
      glucose. Postprandial respiratory quotient and expired (13)CO(2) were higher in
      the SPI-AA than in the casein-AA group, as the differences were similarly
      observed in mice fed SPI-H and casein diet. No significant differences were
      observed in the postprandial respiratory quotient and expired (13)CO(2) between
      the SPI-H and SPI-HET group. In conclusion, this study on food-restricted mice
      indicates that the amino acid mixtures simulating SPI-H or casein could affect
      postprandial energy metabolism in diabetic mice, as observed in those fed SPI-H
      or casein in the form of peptide or protein.

PMID- 14730127
TI  - Induction of anti-inflammatory responses by dietary Momordica charantia L.
      (bitter gourd).
AB  - We assessed the immunomodulatory activity of Momordica charantia L. (bitter
      gourd), a vegetable that has been reported to possess various bioactivities. We
      examined the effect of bitter gourd on intestinal immunity by monitoring the TGF
      beta and IL-7 secretion from Caco-2 cells and the IL-10 and IL-12 secretion from
      THP-1 cells that are used as in vitro models of the intestinal epithelium and
      monocyte/macrophages, respectively. We also determined the in vivo immunological
      responses of rats fed on bitter gourd for 3 weeks. We found that bitter gourd
      induced a decrease in the intestinal secretion of IL-7 and an increase in the
      secretions of TGF-beta and IL-10, these effects reflecting the bitter gourd
      induced changes in systemic immunity, i.e., a decrease in the number of
      lymphocytes, increases in the populations of Th cells and NK cells, and increase
      in the Ig production of lymphocytes. Dietary bitter gourd may therefore induce
      both intestinal and also systemic anti-inflammatory responses.

PMID- 14730128
TI  - Effects of voluntary resistance exercise and high-protein snack on bone mass,
      composition, and strength in rats given glucocorticoid injections.
AB  - We examined the effects of a voluntary resistance exercise (climbing) together
      with high-protein snacks (60% protein) on bone mass and strength in rats given
      glucocorticoid-injections (2 mg/kg/day) as a model of age-related osteopenia.
      Fifty-two male Sprague-Dawley rats, 8 weeks age, were assigned to exercise or
      sedentary groups. These groups were further divided into groups that received no
      snack, snack during activity or a snack during rest. All groups were meal-fed
      7:30-8:30 h and 19:30-20:30 h and the snack was fed 23:30-0:30 h (active) or
      11:30-12:30 h (resting). Energy and protein intake were approximately equal in
      all groups. The exercise groups were allowed to climb a wire-mesh tower cage (phi
      20 cm x 200 cm) to drink water from a bottle set at the top. Weight gain during
      the 8-week experimental period was inhibited by a glucocorticoid-injection. Bone
      mass and strength were increased by climbing exercise with a high-protein snack,
      while no effect of snack nor any effect of snack timing was observed. Bone
      weight, calcium content and protein content were positively correlated to maximum
      load or structural stiffness. These results suggest that resistance exercise and
      high-protein supplementation may be a preventive therapy for osteoporosis
      associated with aging.

PMID- 14730129
TI  - Transaldolase/glucose-6-phosphate isomerase bifunctional enzyme and ribulokinase
      as factors to increase xylitol production from D-arabitol in Gluconobacter
      oxydans.
AB  - Xylitol production from D-arabitol by the membrane and soluble fractions of
      Gluconobacter oxydans was investigated. Two proteins in the soluble fraction were
      found to have the ability to increase xylitol production. Both of these xylitol
      increasing factors were purified, and on the basis of their NH(2)-terminal amino
      acid sequences the genes encoding both of the factors were cloned. Expression of
      the cloned genes in Escherichia coli showed that one of the xylitol-increasing
      factors is the bifunctional enzyme transaldolase/glucose-6-phosphate isomerase,
      and the other is ribulokinase. Using membrane and soluble fractions of G.
      oxydans, 3.8 g/l of xylitol were produced from 10 g/l D-arabitol after incubation
      for 40 h, and addition of purified recombinant transaldolase/glucose-6-phosphate
      isomerase or ribulokinase increased xylitol to 5.4 g/l respectively, confirming
      the identity of the xylitol-increasing factors.

PMID- 14730130
TI  - Variable interactions between sucrose non-fermented 1-related protein kinases and
      regulatory proteins in higher plants.
AB  - WPK4 is a sucrose non-fermented 1 (SNF1)-related wheat protein kinase, and was
      previously reported to interact with 14-3-3 proteins. We identified four
      Arabidopsis thaliana WPK4-like genes, and designated them AtWL1 through AtWL4.
      Yeast two-hybrid analysis, however, indicated that none of the AtWLs interacted
      with any of A. thaliana 14-3-3 (At14-3-3) proteins, although WPK4 itself
      interacted with six of them. Structurally, AtWLs were classified into a
      subfamiliy of AtCIPK, which generally interacts with calucineurin B-like proteins
      (CBL). This was also the case for AtWL1 and AtWL2, showing an efficient
      interaction with AtCBL2. In contrast, WPK4 interacted with none of the CBLs. In
      addition, to ascertain the possible interaction in vivo, expression of those
      genes was examined with a promoter-GUS assay. These results suggested that the
      interacting partner of SNF1-related protein kinases varies among plant species,
      and that, in the case of A. thaliana, it was CBLs, some of which were predicted
      to broadly regulate multiple CIPKs.

PMID- 14730131
TI  - Neurite outgrowth-stimulating activities of beta-casomorphins in Neuro-2a mouse
      neuroblastoma cells.
AB  - Endogenous opioid peptides and opiate drugs are known to affect the development
      of the nervous system. beta-Casomorphins (beta-CMs) belong to a family of
      exogenous opioid peptides derived from the milk protein beta-casein by
      proteolytic fragmentation. We investigated the effects of various fragments and
      analogues of beta-CM on neurite outgrowth in Neuro-2a mouse neuroblastoma cells.
      The fragments beta-CM-5 to -9 and beta-CM-5 amide stimulated neurite outgrowth.
      Fragments shorter than beta-CM-5 (beta-CM-3, -4, and beta-CM-4 amide) and longer
      than beta-CM-9 (beta-CM-13 and -21) had no effects. The activity of beta-CMs to
      promote neurite outgrowth does not correlate with their opioid activity in guinea
      pig ileum. The effect of the most potent fragment, beta-CM-5, was prevented by
      the micro-opioid receptor-selective antagonist D-Phe-Cys(2)-Tyr(3)-D-Trp-Orn(5)
      Thr(6)-Pen(7)-Thr(8)-NH(2) (CTOP), or by pretreatment with pertussis toxin. These
      results suggest that the stimulatory effects of beta-CMs on neurite outgrowth
      were mediated through G protein-coupled micro-opioid receptors.

PMID- 14730132
TI  - Enhancing effect of lipids and emulsifiers on the accumulation of quercetin
      metabolites in blood plasma after the short-term ingestion of onion by rats.
AB  - The effects of co-ingested lipids and emulsifiers on the accumulation of
      quercetin metabolites in blood plasma after the short-term ingestion of onion by
      rats were investigated. Plasma extracts of rats that had been fed onion
      containing diets for one and two weeks were analyzed by HPLC with electrochemical
      detection after a treatment with sulfatase/beta-glucuronidase. Almost all of the
      quercetin metabolites in the plasma were sulfate/glucuronide conjugates of
      quercetin and isorhamnetin. More than 4.6% (w/w) of soybean oil in the diets
      significantly enhanced the accumulation of quercetin metabolites in the plasma.
      Fish oil and beef tallow increased this to an extent similar to that with soybean
      oil, and lecithin was more effective than the other three lipids. Two
      emulsifiers, sodium caseinate and sucrose fatty acid ester, also showed an
      enhancing effect on the accumulation of quercetin metabolites. These results
      indicate that co-ingested lipids and emulsifiers could enhance the
      bioavailability of quercetin glucosides in onion.

PMID- 14730133
TI  - Synthesis and activity of pyrimidinylpropenamide antibiotics: the alkyl analogues
      of sparsomycin.
AB  - Facile syntheses of sparsomycin (3) and its four analogues (4-7) based on
      diastereoselective oxidation of sulfide, sulfenylation, and coupling of 6
      methyluracylacryllic acid with monooxodithioacetal amine, are described. Studies
      on the biological activity of morphological reversion on src(ts)-NRK cells were
      also carried out.

PMID- 14730134
TI  - Anti-cariogenic properties of a water-soluble extract from cacao.
AB  - The addition of a water-soluble extract from cacao-extracted powder (CEPWS) to a
      cariogenic model food, a white chocolate-like diet that contains 35% sucrose,
      significantly reduced caries scores in SPF rats infected with Streptococcus
      sobrinus 6715, compared to control rats fed a white chocolate-like diet. CEPWS
      markedly inhibited water-insoluble glucan (WIG) synthesis through crude
      glucosyltransferases (GTFs) from Streptococcus sobrinus B13N in vitro. GTF
      inhibitor(s) in CEPWS was prepared through three-step fractionation, and was
      termed CEPWS-BT, which is a high molecular weight (>10 kDa) heat-stable matrix of
      sugar, protein, and polyphenol. When the inhibitory effect of CEPWS-BT on glucan
      synthesis was examined using the purified GTF-I, GTF-T, and GTF-U enzymes from S.
      sobrinus B13N, significant reduction in GTF-I and GTF-T activity as a result of
      adding CEPWS-BT at low concentrations was observed. These results suggest that
      the addition of CEPWS to cariogenic food could be useful in controlling dental
      caries.

PMID- 14730135
TI  - Genomic cloning of ribonucleases in Nicotiana glutinosa leaves, as induced in
      response to wounding or to TMV-infection, and characterization of their
      promoters.
AB  - We previously cloned two distinct cDNA clones, NGR1 and NGR3, encoding S-like
      ribonucleases (RNases) induced by wounding and tobacco mosaic virus (TMV)
      infection, respectively, in Nicotiana glutinosa leaves. To gain insight into the
      regulatory mechanism of the RNase genes, we analyzed nucleotide sequences of the
      genes ngr1 (4.1 kbp) and ngr3 (5.3 kbp), containing their structural genes as
      well as 5'-flanking regions. The ngr1 gene is organized in three exons with two
      intervening introns, and ngr3 has four exons interrupted by three introns. Primer
      extension analyses localized single transcription initiation sites at -32 and -99
      upstream of the translation initiation codons ATG in the genes ngr1 and ngr3,
      respectively. The beta-glucuronidase (GUS) reporter gene analysis with serial 5'
      deletion mutants as well as a gel shift assay defined the wound-responsive region
      at residues -509 to -288 in gene ngr1 and a TMV-responsive region at the residues
      -401 to -174 in ngr3, respectively. Sequence search using PLACE and PlantCARE
      data bases showed that a wound-responsive element: the WUN-motif, occurs within
      the wound-responsive region in ngr1, while ngr3 contains several potential cis
      regulating elements, such as the elicitor responsiveness element: the W-box, a
      TMV responsive element: GT1, and the WUN-motif at positions between -401 and 
      174. These findings suggested that some of these cis-elements may be involved in
      inducible expressions of ngr1 and ngr3. Furthermore, the gel shift assay
      suggested that the dissociation of protein factor(s) upon TMV-infection from the
      regulatory region may cause an inducible expression of ngr3.

PMID- 14730136
TI  - Synthetic racemate and enantiomers of cytosporone E, a metabolite of an
      endophytic fungus, show indistinguishably weak antimicrobial activity.
AB  - The racemate and the enantiomers of cytosporone E [3-heptyl-4,5,6
      trihydroxyphthalide (1)], a metabolite of the endophytic fungus, CR200 (Cytospora
      sp.), were synthesized. The key steps were (i) Sharpless asymmetric
      dihydroxylation of an alkene (8) and (ii) HPLC separation of the enantiomers of
      tert-butyldimethylsilyl ether (12) on a chiral stationary phase. The racemate and
      enantiomers of cytosporone E showed only weak antimicrobial activity with no
      difference among them.

PMID- 14730137
TI  - SS33410, an inhibitor of V-ATPase, blocks intracellular protein transport of the
      VSV-G protein in the Golgi compartment.
AB  - An earlier report suggested that SS33410, structurally related to folimycin and
      bafilomycin A(1), blocked secretion of the glycoprotein (G protein) of vesicular
      stomatitis virus (VSV) into the medium and, instead, G protein was accumulated
      intracellulary. To identify the inhibition site of SS33410 in intracellular
      protein transport, I have analyzed the oligosaccharide chain structure of the
      intracellularly accumulated G protein. In SS33410-treated VSV-infected cells, G
      protein oligosaccharide was suggested to have a composition of GlcNAc-Man(5)
      GlcNAc(2) as analyzed by Bio-Gel P-4 column chromatography following digestion
      with alpha-mannosidase, beta-N-acetylhexosaminidase, and then with alpha
      mannosidase. SS33410 specifically inhibited vacuolar-type ATPase (V-ATPase).
      These studies thus suggest that SS33410 blocks the intracellular protein
      transport before the step of trimming by mannosidase II, which is confined to the
      medial Golgi compartment.

PMID- 14730138
TI  - Purification, characterization, and molecular cloning of a pyranose oxidase from
      the fruit body of the basidiomycete, Tricholoma matsutake.
AB  - A new H(2)O(2)-generating pyranose oxidase was purified as a strong antifungal
      protein from an arbuscular mycorrhizal fungus, Tricholoma matsutake. The protein
      showed a molecular mass of 250 kDa in gel filtration, and probably consisted of
      four identical 62 kDa subunits. The protein contained flavin moiety and it
      oxidized D-glucose at position C-2. H(2)O(2) and D-glucosone produced by the
      pyranose oxidase reaction showed antifungal activity, suggesting these compounds
      were the molecular basis of the antifungal property. The V(max), K(m), and k(cat)
      for D-glucose were calculated to be 26.6 U/mg protein, 1.28 mM, and 111/s,
      respectively. The enzyme was optimally active at pH 7.5 to 8.0 and at 50 degrees
      C. The preferred substrate was D-glucose, but 1,5-anhydro-D-glucitol, L-sorbose,
      and D-xylose were also oxidized at a moderate level. The cDNA encodes a protein
      consisting of 564 amino acids, showing 35.1% identity to Coriolus versicolor
      pyranose oxidase. The recombinant protein was used for raising the antibody.

PMID- 14730139
TI  - Identification and expression analysis of cDNA encoding a chloroplast
      recombination protein REC1, the chloroplast RecA homologue in Chlamydomonas
      reinhardtii.
AB  - Chloroplasts of plant cells have their own genome, and a basic recombination
      protein homologous to the eubacterial RecA was suggested to be involved in the
      perpetuation of chloroplast DNA. A candidate cDNA sequence encoding the
      chloroplast RecA protein was identified from the Kazusa EST database for the
      unicellular green alga, Chlamydomonas reinhardtii
      (http://www.kazusa.or.jp/en/plant/chlamy/EST/). Analysis of the cDNA sequence
      identified an open reading frame (ORF) of 414 amino acids encoding a eubacteria
      type RecA protein. Thus the corresponding gene was named REC1. The predicted
      protein contains an N-terminal extension that does not show any similarity with
      other RecA proteins. Transient expression of a REC1-sGFP (green fluorescent
      protein) fusion construct in tobacco cells has indicated that this N-terminal
      sequence functions as a transit peptide for import into chloroplasts. Since DNA
      damaging reagents induced the REC1 mRNA, REC1 was suggested to have roles in DNA
      recombination and repair of the chloroplast DNA in C. reinhardtii.

PMID- 14730140
TI  - Pyrazolecarboxylic acid derivative induces systemic acquired resistance in
      tobacco.
AB  - Systemic acquired resistance (SAR) is a potent innate immunity system in plants
      that is induced through asalicylic acid (SA)-mediated pathway. Here, we
      characterized 3-chloro-1-methyl-1H-pyrazole-5-carboxylic acid (CMPA) as an
      effective SAR inducer in tobacco. Soil drench application of CMPA induced PR gene
      expression and a broad range of disease resistance without antibacterial activity
      in tobacco. Both analysis of CMPA's effects on NahG transgenic tobacco plants and
      SA measurement in wild-type plants indicated that CMPA-induced resistance
      enhancement does not require SA. Therefore, it is suggested that CMPA induces SAR
      by triggering the signaling at the same level as or downstream of SA accumulation
      as do both benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester and N
      cyanomethyl-2-chloroisonicotinamide.

PMID- 14730141
TI  - The amino acid sequence of satyr tragopan lysozyme and its activity.
AB  - The amino acid sequence of satyr tragopan lysozyme and its activity was analyzed.
      Carboxymethylated lysozyme was digested with trypsin and the resulting peptides
      were sequenced. The established amino acid sequence had three amino acid
      substitutions at positions 103 (Asn to Ser), 106 (Ser to Asn), and 121 (His to
      Gln) comparing with Temminck's tragopan lysozyme and five amino acid
      substitutions at positions 3 (Phe to Tyr), 15 (His to Leu), 41 (Gln to His), 101
      (Asp to Gly) and 103 (Asn to Ser) with chicken lysozyme. The time course analysis
      using N-acetylglucosamine pentamer as a substrate showed a decrease of binding
      free energy change, 1.1 kcal/mol at subsite A and 0.2 kcal/mol at subsite B,
      between satyr tragopan and chicken lysozymes. This was assumed to be responsible
      for the amino acid substitutions at subsite A-B at position 101 (Asp to Gly),
      however another substitution at position 103 (Asn to Ser) considered not to
      affect the change of the substrate binding affinity by the observation of
      identical time course of satyr tragopan lysozyme with turkey and Temminck's
      tragopan lysozymes that carried the identical amino acids with chicken lysozyme
      at this position. These results indicate that the observed decrease of binding
      free energy change at subsites A-B of satyr tragopan lysozyme was responsible for
      the amino acid substitution at position 101 (Asp to Gly).

PMID- 14730142
TI  - Synthesis of the sex pheromone of the citrus mealybug, Pseudococcus cryptus.
AB  - The sex pheromone of the citrus mealybug (Pseudococcus cryptus), [(1R,3R)-3
      isopropenyl-2,2-dimethylcyclobutyl]methyl 3-methyl-3-butenoate, was synthesized
      from (+)-alpha-pinene in five operational steps in a 43% overall yield. The
      synthetic pheromone was identical with the natural pheromone in (1)H-NMR and mass
      spectroscopic properties, and showed almost the same pheromonal activity as the
      natural pheromone.

PMID- 14730143
TI  - Production of hydrogen peroxide by polyphenols and polyphenol-rich beverages
      under quasi-physiological conditions.
AB  - To investigate the ability of the production of H(2)O(2) by polyphenols, we
      incubated various phenolic compounds and natural polyphenols under a quasi
      physiological pH and temperature (pH 7.4, 37 degrees C), and then measured the
      formation of H(2)O(2) by the ferrous ion oxidation-xylenol orange assay.
      Pyrocatechol, hydroquinone, pyrogallol, 1,2,4-benzenetriol, and polyphenols such
      as catechins yielded a significant amount of H(2)O(2). We also examined the
      effects of a metal chelator, pH, and O(2) on the H(2)O(2)-generating property,
      and the generation of H(2)O(2) by the polyphenol-rich beverages, green tea, black
      tea, and coffee, was determined. The features of the H(2)O(2)-generating property
      of green tea, black tea, and coffee were in good agreement with that of phenolic
      compounds, suggesting that polyphenols are responsible for the generation of
      H(2)O(2) in beverages. From the results, the possible significances of the
      H(2)O(2)-generating property of polyphenols for biological systems are discussed.

PMID- 14730144
TI  - Suppression by Hydrangeae Dulcis Folium of D-galactosamine-induced liver injury
      in vitro and in vivo.
AB  - Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla
      SER. var. thunbergii MAKINO, suppressed D-galactosamine-induced liver injury by
      85.2% when added to the diet at 1% and fed to rats for fifteen days. The
      hepatoprotective effect is more potent than that of a milk thistle extract and
      turmeric powder. Some fractionated extracts showed hepatoprotective activity in
      the D-galactosamine-induced in vitro liver injury model.

PMID- 14730145
TI  - Oxygenated lycopene and dehydrated lutein in tomato puree.
AB  - Oxygenated lycopenes, (2S*,5S*,6R*)-2,6-cyclolycopene-1-methoxy-5-ol,
      (2S*,5S*,6R*)-1,16-didehydro-2,6-cyclolycopene-5-ol and (3R,6'R)-3-hydroxy-3',4'
      didehydro-beta,gamma-carotene (anhydrolutein I) were isolated from tomato puree.
      The structures of these compounds were elucidated on the basis of spectroscopic
      evidence.

PMID- 14730146
TI  - Coenzyme specificity of enzymes in the oxidative pentose phosphate pathway of
      Gluconobacter oxydans.
AB  - The coenzyme specificity of enzymes in the oxidative pentose phosphate pathway of
      Gluconobacter oxydans was investigated. By investigation of the activities of
      glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase
      (6PGDH) in the soluble fraction of G. oxydans, and cloning and expression of
      genes in Escherichia coli, it was found that both G6PDH and 6PGDH have NAD/NADP
      dual coenzyme specificities. It was suggested that the pentose phosphate pathway
      is responsible for NADH regeneration in G. oxydans.

PMID- 14730147
TI  - Cellulose as extracellular polysaccharide of hot spring sulfur-turf bacterial
      mat.
AB  - The carbohydrate fraction of a hot spring sulfur-turf bacterial mat was shown to
      contain cellulose by the examination of neutral sugar composition, methylation
      analysis, and the identification of free oligosacchrides obtained from an
      acetolyzate of the desulfurized sulfur-turf mat. This suggested that the sulfur
      oxidizing bacteria composing the sulfur-turf were producers of cellulose.

PMID- 14730148
TI  - Specific incorporation of L-glutamine into volicitin in the regurgitant of
      Spodoptera litura.
AB  - Volicitin, [N-(17-hydroxylinolenoyl)-L-glutamine], was identified as an elicitor
      of plant volatiles from a Spodoptera exigua regurgitant. It has been proposed
      that gut microbes synthesize volicitin from glutamine, a predominant amino acid
      component in the insect gut. However, we found that glutamine was not a major
      component in the regurgitant of Spodoptera litura, although L-glutamine was
      exclusively incorporated into volicitin by S. litura fed on diets enriched with
      various amino acids. This selectivity of glutamine as a substrate was not due to
      a dominant occurrence in the insect gut.

PMID- 14730149
TI  - Efficient synthesis of akolactone A via Pd-catalyzed carbonylation.
AB  - The first synthesis of (+)- and (-)-akolactone A is described by using Pd
      catalyzed carbonylation. A comparison of the optical rotation of both enantiomers
      of akolactone A and the natural compound suggests that the absolute configuration
      at the 4-position of akolactone A is R.

PMID- 14730150
TI  - Transformation of Aspergillus aculeatus using the drug resistance gene of
      Aspergillus oryzae and the pyrG gene of Aspergillus nidulans.
AB  - Transformation systems for Aspergillus aculeatus has been developed, based on the
      use of the pyrithiamine resistance gene of Aspergillus oryzae and the orotidine
      5'-monophosphate decarboxylase gene (pyrG) of Aspergillus nidulans. An A.
      aculeatus mutant which can be transformed effectively by the A. nidulans pyrG
      gene was isolated as a transformation host. This is the first report of
      transformation of A. aculeatus.

PMID- 14730151
TI  - Stereochemistry of 2-phenylethylamine oxidation catalyzed by bacterial copper
      amine oxidase.
AB  - The stereochemical course of the reaction catalyzed by a copper amine oxidase
      from Arthrobacter globiformis has been investigated using 2-phenylethylamine
      stereospecifically deuterium-labeled at the C1 position. Measurements of
      deuterium content in the product, phenylacetaldehyde, by gas chromatography-mass
      spectrometry revealed stereospecific abstraction of the pro-S hydrogen during the
      enzymatic oxidation, as predicted from the structure modeling for the enzyme
      bound substrate.

PMID- 14730152
TI  - Protein profile of symbiotic bacteria Mesorhizobium loti MAFF303099 in mid-growth
      phase.
AB  - Expressed proteins in cultured symbiotic bacteria (Mesorhizobium loti MAFF303099)
      in the mid-growth phase were proteomically analyzed by two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) and capillary high-performance
      liquid chromatography coupled with an ion-trap mass spectrometry (MS). The genome
      sequence data of M. loti were used to identify the analyzed proteins. We
      identified 114 of the 127 proteins analyzed on 2D-PAGE gel with some
      microheterogenities which were caused by post-translational modifications.

PMID- 14730153
TI  - A transient RNA interference assay system using Arabidopsis protoplasts.
AB  - Double-stranded RNA (dsRNA) induces sequence-specific gene silencing in
      eukaryotes through a process known as RNA interference (RNAi). RNAi is now used
      as a powerful tool for functional genomics in many eukaryotes, including plants.
      We herein report a dsRNA-mediated transient RNAi assay system using protoplasts
      from Arabidopsis mesophyll cells and suspension-cultured cells (cell line T87).
      Introduction of dsRNA into protoplasts led to marked silencing of target
      transgenes. Our assay system would provide a convenient and efficient way to
      induce RNAi in protoplasts of the model plant Arabidopsis thaliana.

PMID- 14730154
TI  - Cloning and characterization of a Caenorhabditis elegans cDNA encoding a new
      insulin/IGF-like peptide.
AB  - A Caenorhabditis elegans cDNA encoding a new insulin/IGF-like peptide was cloned
      and examined. The predicted peptide shows significant sequence similarity with
      the peptide Ceinsulin-1 reported previously and contains a characteristic
      insertion consisting of three residues in the putative B domain as with the
      Ceinsulin-1. The gene expression pattern during development is almost identical
      to that of Ceinsulin-1. The predicted tertiary structure of the peptide is quite
      similar to that of Ceinsulin-1, and their predicted receptor-recognition surfaces
      also closely match. These facts suggest that both peptides could recognize the
      same receptor.

PMID- 14730155
TI  - Tissue distribution and intracellular localization of catechins in tea leaves.
AB  - We investigated the leaf tissue and cellular morphology of tea (Camellia
      sinensis). Osmiophilic material, presumably catechins, was present in mesophyll
      cells, but not in epidermal cells. Electron microscopy showed that catechins were
      localized to restricted regions within the central vacuoles. In addition, two
      kinds of small vacuoles of 0.5-3 microm were present in mesophyll cells. One
      vacuole had catechins within its whole lumen, while the other had an electron
      lucent lumen. We found fusion profiles between a large central vacuole and these
      small vacuoles. We propose that after catechins are synthesized, they are
      incorporated into small vacuoles and transported to the large central vacuoles.

PMID- 14730156
TI  - 24-hour electrocardiogram before and during cisapride treatment in neonates and
      infants.
AB  - We studied prospectively the effects of cisapride on heart rate and rhythm using
      standard ECG and 24-hour ECG recordings in term and preterm neonates and infants.
      We studied subjects with gastroesophageal reflux disease (apparent life
      threatening events, apneas, bradycardias) before and 3 days after starting
      cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for
      determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24
      hour ECG recordings for analysis of heart rate, heart rate variability, and heart
      rhythm. Fourteen term and 17 preterm subjects (gestational age range 28-36 weeks)
      were studied at a median chronological age of 29 (range 3-132) days. Cisapride
      significantly increased the QTc in preterm infants (before vs. after: 408 +/- 7
      vs. 433 +/- 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms
      before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had
      a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no
      relevant arrhythmias were documented on Holter recordings. Cisapride
      significantly decreased peak and mean heart rates of all study subjects without
      affecting the heart rate variability, while it increased the minimal heart rate
      of preterm infants only (before vs. after: 66 +/- 5 vs. 78 +/- 5 bpm, p = 0.02).
      The maximally measured R-R intervals (pauses) decreased after cisapride in
      preterm infants (before vs. after: 1.33 +/- 0.2 s vs. 1.05 +/- 0.2 s, p = 0.04).
      Although cisapride did cause a significant prolongation of the ventricular action
      potential duration in preterm infants, the QTd remained unaffected, and no
      clinically relevant arrhythmias were documented in this small sample. On the
      other hand, cisapride had a direct lowering effect on the maximal and mean heart
      rates of both term and preterm infants, while the drug increased the minimal
      heart rate and reduced the severity of bradycardia episodes in preterm infants.

PMID- 14730157
TI  - Endogenous distress in ventilated full-term newborns with acute respiratory
      failure.
AB  - OBJECTIVE: The main rationale behind the continuous analgesia/sedation currently
      practiced in the treatment of neonates with severe respiratory failure in
      intensive care is an attempt at shielding the sick newborn from exogenous stress
      and pain caused by diagnostic and therapeutic interventions. Until now, however,
      the factors which influence endogenous, disease-related distress have been
      largely ignored. METHOD: We retrospectively studied the daily need for analgesics
      and sedatives (fentanyl, midazolam, pentobarbital, thiopental) of 40 full-term
      newborns with severe respiratory failure who had been ventilated for at least 48
      h over an observational period of 2-5 days. Dosing of the analgesics and
      sedatives was based on a neonatal sedation score for ventilated infants. These
      daily amounts were converted to a normative comparative dose (analgesic/sedative
      need = ASN) and compared with the oxygenation index (OI) as a measure of the
      degree of pulmonary insufficiency. RESULTS: Depending on the duration of
      ventilation, an increasingly close correlation between the ASN and the OI was
      detected: the index of correlation (r) was detected to be 0.65 on the second day,
      but increased up to 0.94 after 5 days. The subgroup of patients who had been
      ventilated for more than 3 days (n = 8) consistently showed a very high
      correlation, ranging from r = 0.86 to r = 0.94. CONCLUSION: Our results indicate
      a direct relationship between severity of pulmonary failure (expressed as OI) and
      degree of disease-related distress (reflected by ASN). This supports the
      hypothesis that in full-term neonates under mandatory intensive care for severe
      respiratory failure, endogenous distress caused by the primary disease itself, in
      addition to exogenous distress caused by therapeutic and diagnostic
      interventions, is key factor for the determination of the required amount of
      analgesic and sedative drugs.

PMID- 14730158
TI  - The unstable detrusor.
AB  - The unstable detrusor (detrusor instability), a common condition in men and
      women, causes significant morbidity in sufferers and a great financial expense to
      health care providers. The condition is associated with symptoms of urinary
      frequency, urgency and urge incontinence. The embarrassing nature of these
      symptoms means patients are often reluctant to seek medical help and as a
      consequence there is under-reporting. Epidemiological studies are difficult to
      perform but appear to show that incidence increases with age and that the
      unstable detrusor is the commonest cause of male urinary incontinence. The
      aetiology is still much debated with reasoned arguments for both neurogenic and
      myogenic causes, though in truth, the likely explanation is multifactorial rather
      than a single underlying pathological process. The diagnosis can only be made on
      urodynamic testing. Before deciding on suitable treatment, the clinician must
      assess the disease severity and also its impact on patient quality of life. This
      is because perceived improvement in patient quality of life must outweigh any
      potential morbidity associated with treatment. Pharmacotherapy is based on
      blocking bladder muscarinic receptors. Unfortunately, no treatment is bladder
      specific and therefore most drug therapies have unwanted systemic anticholinergic
      side effects. Surgical treatment often involves a degree of bladder denervation
      to reduce bladder activity. This can consequently produce voiding difficulties
      which necessitate patients to self-catheterise on a longterm basis.

PMID- 14730159
TI  - Estimated blood loss underestimates calculated blood loss during radical
      retropubic prostatectomy.
AB  - OBJECTIVE: To compare the calculated blood loss for radical retropubic
      prostatectomy (RRP) with the anesthesiologist's and operating surgeon's estimates
      of operative blood loss. METHODS: A retrospective review of 52 consecutive
      patients undergoing RRP between January 1999 and February 2000 was performed.
      Patient charts were reviewed for preoperative hemoglobin (Hgb(i)), preoperative
      hematocrit (Hct(i)), body weight (Wt), anesthesiologist's and surgeon's estimated
      blood loss (EBL(A) and EBL(S)), and postoperative day one morning hemoglobin
      (Hgb(f)) and hematocrit (Hct(f)). For each patient, the actual blood loss (ABL),
      i.e., the amount of blood that left the patient's body, was calculated as the
      average ABL(n) resulting from two computations of the following formula: ABL(n) =
      (EBV x (H(i) - H(f)) / ((H(i) + H(f))/2) + (500 x T(u)) where: (1) estimated
      blood volume (EBV) is assumed to be 70 cm(3)/kg; (2) H(i) and H(f) represent
      Hgb(i )and Hgb(f) for one computation and Hct(i) and Hct(f) for the second
      computation, and (3) T(u) is the sum of autologous whole blood (AWB), packed red
      blood cells (PRBC), and cell saver (CS) units transfused. For each patient, ABL
      was compared with EBL(A) and EBL(S). Descriptive statistics of the pooled data
      were calculated. RESULTS: The mean (+/- SD) age was 60 +/- 7.1 years. The mean
      ABL was 2,774 +/- 1,014 cm(3). Patients received an average of 1.96 U CS, 0.14 U
      PRBC, and 0.42 U AWB. Five patients (9.6%) were exposed to homologous blood. The
      average ABL(net) (i.e. ABL reduced by the amount of CS returned) was 1,794 +/-
      806 cm(3). EBL(A) and EBL(S) were 1,337 +/- 676 and 1,300 +/- 658 cm(3),
      respectively. CONCLUSION: During radical retropubic prostatectomy,
      anesthesiologists and urologists both appear to underestimate blood loss as
      determined by standard calculation.

PMID- 14730160
TI  - Vesicourethral anastomotic strictures after radical retropubic prostatectomy: the
      experience of a single institution.
AB  - OBJECTIVE: Stricture of the vesicourethral anastomosis remains a well-documented
      complication after radical retropubic prostatectomy. MATERIALS AND METHODS: We
      performed a retrospective study of 294 patients with prostate cancer who
      underwent radical retropubic prostatectomy. Possible correlations between
      anastomotic stricture formation, tumor stage, positive surgical margins, number
      of anastomotic sutures, bladder neck preservation, urine leakage, previous
      prostate surgery and/or intraoperative blood loss were examined. RESULTS: An
      anastomotic stricture was found in 18 cases (6%) requiring some kind of
      treatment. In 10 patients (56%), the bladder neck stricture occurred within 3
      months after surgery, in 5 (28%) at 4-12 months after surgery and in 3 (16%) more
      than 12 months after surgery. Intraoperative blood loss (>1,000 ml) was found to
      be significantly correlated with urinary leakage (p < 0.001) and both correlated
      with anastomotic stricture formation (p < 0.005). CONCLUSION: Excessive
      intraoperative blood loss (>1,000 ml) and urine leakage was found to be
      significantly correlated to the formation of anastomotic stricture following
      radical retropubic prostatectomy.

PMID- 14730162
TI  - Squamous cell carcinoma of the prostate. A report of 6 cases.
AB  - Squamous cell carcinoma of the prostate is uncommon. In an attempt to assess the
      incidence of squamous cell carcinoma of the prostate, we searched the records of
      the Saskatchewan Cancer Agency over the past 30 years. Using strict diagnostic
      criteria a total of 6 cases of pure squamous cell carcinoma among 13,497 cases of
      prostatic carcinoma were identified. The ages of these patients ranged from 42 to
      85 years. The survival rates of these cases ranged from 1 to 13 months.

PMID- 14730161
TI  - Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between
      neoadjuvant and adjuvant hormonotherapy.
AB  - INTRODUCTION: The aim of this study was to retrospectively compare the clinical
      outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing
      neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant
      hormonotherapy with external beam radiotherapy. PATIENTS AND METHODS: One hundred
      patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph
      nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic
      cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin,
      starting 2 months before radiotherapy and continuing until the end of
      irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant
      goserelin until disease progression, if present. RESULTS: Patients undergoing
      adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant
      therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a
      lower incidence of biochemical failures (p = 0.0170), a lower incidence of
      hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease
      free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did
      not show a significant correlation with any of the end points analyzed. To the
      contrary, patients with tumor <15 mm showed a better local control (p = 0.0347)
      and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between
      initial PSA level and incidence of hematogenous metastases was observed (p =
      0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence
      of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with
      complete clinical response showed a lower incidence of biochemical failures (p =
      0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free
      survival (p = 0.0554). At multivariate analysis, a correlation between Gleason
      score and incidence of metastases (p = 0.0232), and between tumor diameter and
      local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was
      recorded. CONCLUSIONS: In patients with cT3N0M0 prostate carcinoma, prolonged
      hormonotherapy was shown to be significantly correlated with biochemical failure
      free survival and distant metastasis-free survival. Furthermore, tumor size had a
      significant impact on biochemical failure-free survival as well as on local
      control.

PMID- 14730163
TI  - Treatment of benign prostatic hyperplasia through transurethral needle ablation
      (TUNA). Review of the literature and six years of clinical experience.
AB  - Following FDA clearance and the establishment of Medicare coverage, transurethral
      needle ablation (TUNA) has become an established and widely-adopted treatment
      method for BPH in the USA. Germany is lagging behind at present, though a change
      can also be recognized there. The lack of long-term data has often been
      criticized. This review presents an overview of clinical outcomes of TUNA, long
      term results and patient selection criteria.

PMID- 14730164
TI  - The Band Electrode: ongoing experience with a novel TURP loop to improve
      hemostasis in 265 patients.
AB  - INTRODUCTION: Intraoperative bleeding, one of the major complications of
      conventional transurethral resection of the prostate (TURP), has led to a search
      for various alternative methods of tissue ablation in patients with benign
      prostatic hyperplasia. In 1996, we introduced the newly designed Band Electrode,
      which combines a high degree of resection efficiency with a better hemostasis.
      MATERIAL AND METHODS: 265 consecutive patients with prostatism underwent TURP
      with the Band Electrode. This modified loop electrode does not consist of a thin
      wire but is rather a flat metal band with a width of 1.2 mm. International
      prostate symptom score (IPSS), Life Quality Index (L), peak urine flow and
      postvoid residual urine were evaluated pre- and postoperatively. Additionally,
      electrical parameters have been recorded with a specially designed high-frequency
      generator. RESULTS: Median IPSS decreased from 23 preoperatively to 8 and 9 at 12
      (n = 194) and 24 months (n = 172), respectively (p < 0.001). Life Quality Index
      (L) dropped from 4 to 2 and 2, respectively (p < 0.001). Peak urine flow
      increased from 8.2 ml/s to 18.2 (at postoperative day 3), 17.8 and 17.4 ml/s,
      respectively (p < 0.001). Median postvoid residual urine decreased from 77 to 15,
      22 and 21 ml, respectively (p < 0.001). Resected tissue mass averaged 25 (8-102)
      g, resection time was 36.5 (18-82) min. Indwelling catheters were removed 32 (24
      72) h postoperatively. None of the patients required blood transfusions or showed
      signs of a TUR syndrome. Despite a 1.3 times higher power need, the total energy
      application in vivo was comparable to conventional TURP. CONCLUSIONS: This simple
      exchange of active electrodes leads to a superior hemostasis and thus safety in
      TURP. Resection speed, tissue ablation and total energy need remain identical.

PMID- 14730165
TI  - Urodynamic parameters for the diagnosis of bladder outlet obstruction in women.
AB  - INTRODUCTION: Bladder outlet obstruction (BOO) is often overlooked in the
      diagnosis of women with lower urinary tract symptoms. Although the incidence of
      BOO is not high in the female population with lower urinary tract symptoms, a
      correct diagnosis for BOO is important. This study was designed to compare the
      urodynamic parameters in women with bladder outlet obstruction (BOO), stress
      urinary incontinence (SUI) and asymptomatic volunteers. MATERIALS AND METHODS:
      Videourodynamic study was performed in 76 patients who were clinically diagnosed
      as BOO, 265 with stress urinary incontinence (SUI). In addition, 30 asymptomatic
      female volunteers were recruited and served as controls. Voiding pressure
      (P(det.Qmax)), maximum flow rate (Qmax), and urodynamic parameters were compared
      among the BOO, SUI and control groups and the criteria values for BOO in women
      were estimated. RESULTS: BOO was identified in 30 women with bladder outlet
      stricture, 40 women with dysfunctional voiding, and 6 women with high-grade
      cystocele. The mean P(det.Qmax) was significantly higher and the mean Qmax was
      significantly lower in the obstructed groups. When a P(det.Qmax) > or =35 cm
      H(2)O was set as the criteria for BOO, the sensitivity was 96.1% and specificity
      was 89.0%, whereas a P(det.Qmax) of > or =30 cm H(2)O had a sensitivity of 100%
      but the specificity was only 65.5%. If the criteria of BOO was set as P(det.Qmax)
      > or =35 cm H(2)O combined with Qmax < or =15 ml/s, the sensitivity for BOO was
      81.6% and specificity was 93.9%. CONCLUSIONS: Our results demonstrate a
      P(det.Qmax) of > or =30 cm H(2)O is a good index value for screening of female
      BOO. When a P(det.Qmax) of > or =35 cm H(2)O combined with a Qmax < or =15 ml/s
      was found, a high suspicion of BOO should be raised, for which a specificity of
      93.9% and sensitivity of 81.6% for BOO was obtained.

PMID- 14730166
TI  - The prevalence of female sexual dysfunction and potential risk factors that may
      impair sexual function in Turkish women.
AB  - OBJECTIVES: To detect the prevalence of sexual dysfunction, and also to
      investigate possible risk factors that may cause sexual dysfunction in the
      Turkish women. MATERIALS AND METHODS: The study consisted of 179 women between
      the ages of 18 and 66 years living in households from different sociocultural
      areas. The women were divided into 5 groups according to their ages: 18-27 years
      (n = 23), 28-37 years (n = 55), 38-47 years (n = 43), 48-57 years (n = 44) and 58
      67 years (n = 14). Female sexual function was evaluated with a detailed 19-item
      questionnaire to assess desire, arousal, lubrication, orgasm, satisfaction and
      pain. The prevalence of sexual dysfunction was calculated for each domain and
      compared among the groups. In addition, demographic characteristics and medical
      risk factors were assessed in all women, and the findings were compared between
      the women with and without sexual dysfunction. RESULTS: Based on total sexual
      function score, 84 (46.9%) out of 179 women had sexual dysfunction. The
      prevalence of female sexual dysfunction was 21.7% in the ages of 18-27 years,
      25.5% in the ages of 28-37 years, 53.5% in the ages of 38-47 years, 65.9% in the
      ages of 48-57 years and 92.9% in the ages of 58-67 years. The prevalence of
      sexual dysfunction for each domain also increased with age. To investigate
      various factors that may cause female sexual dysfunction, no significant
      differences were detected in smoking history (p = 0.14), marriage age (p = 0.7),
      the presence of previous pelvic surgery (p = 0.09), and contraception methods
      used (p = 0.31). However, sexual dysfunction was observed as significantly higher
      in the presence of older age (p = 0.001), lower educational level (p = 0.012),
      unemployment status (p = 0.017), chronic disease (p = 0.032), multiparity (p =
      0.0027) and menopause status (p = 0.0001). CONCLUSIONS: The prevalence of female
      sexual dysfunction including desire, arousal, lubrication, orgasm, satisfaction
      and pain problems increases with age. In addition, the presence of a lower
      educational level, unemployment status, chronic diseases, multiparity and
      menopause status are important risk factors that may cause sexual dysfunction.

PMID- 14730167
TI  - A new tension-adjustment technique for sling operation: an animal model.
AB  - OBJECTIVE: To investigate the effectiveness of a new tension-adjustment technique
      for postoperative voiding difficulties encountered after sling operations.
      METHOD: To test our new method, urethral obstruction was developed in 5 female
      dogs by modifying the sling operation by exerting more tension on a specially
      prepared polypropylene strip in which a gap had been developed. After filling the
      bladder with isotonic solution, detrusor contractions were induced by pelvic
      nerve stimulations, and urodynamic studies were performed to document the
      urethral obstruction. In each case Foley catheters were inserted into the bladder
      and left in place until the time of tension adjustment. Tension adjustment was
      performed in the 1st, 2nd, 3rd, 4th and 5th weeks postoperatively for dogs 1, 2,
      3, 4, and 5, respectively. RESULTS: On the day of tension adjustment, after
      filling the bladder with isotonic solution and removing the Foley catheter, none
      of the dogs, except dog 3, was able to produce a free flow of urine either
      spontaneously or provoked by detrusor contractions. The release of the prolene
      sutures was readily achieved in all cases except dog 5. In this case, sling
      takedown was achieved after surgical exploration in which the sling location was
      confirmed by following the prolene sutures and Hegar's dilator. After identifying
      the sling, the gap was opened by cutting the prolene sutures, instead of a sling
      incision. Release of the prolene sutures resulted in a distinct drop in the
      urethra with decreased resistance of Hegar's dilator. The improvement in voiding
      was confirmed by postoperative urodynamic studies and was immediate in all cases.
      CONCLUSION: Our new technique for postoperative voiding difficulties encountered
      after sling operation is simple, effective and avoids re-operation in the early
      postoperative period.

PMID- 14730168
TI  - Serum insulin-like growth factor-I and insulin-like growth factor-binding protein
      3 in localized, metastasized prostate cancer and benign prostatic hyperplasia.
AB  - OBJECTIVE: Insulin-like growth factors (IGF-I and IGF-II) are important mitogenic
      peptides and are thought to be significant factors involved in normal and
      malignant cellular proliferation including benign prostatic hyperplasia (BPH) and
      prostate cancer (PC). In particular, the association between IGF-I and PC has
      received much attention. Insulin-like growth factor binding protein-3 (IGFBP-3)
      is the major carrier protein in serum for the IGF-I, thus is an important
      functional modulator of it. On the other hand, one of the functions of prostate
      specific antigen (PSA) is to cleave IGFBP-3. Epidemiological studies have shown
      that decreased levels of serum IGFBP-3 are associated with increased PC risk.
      Controversial results have also been reported on the value of serum IGF-I and/or
      IGFBP-3 in the detection of PC, especially of metastatic PC; as increased,
      decreased or unchanged when compared to BPH. The aim of the present study was to
      investigate whether serum IGF-I and IGFBP-3 levels change in localized and
      metastasized PC cases compared with BPH as the control cases. METHOD: The study
      included 45 BPH, 24 localized PC and 19 metastasized PC cases. Serum IGF-I and
      IGFBP-3 levels were measured by two-site immunoradiometric assay kits, and serum
      total and free PSA levels were assayed by chemiluminescence method. RESULTS:
      Serum IGF-I levels in both localized and metastasized PC cases were similar to
      BPH cases (138.3 +/- 58.2, 137.7 +/- 39.0 and 147.7 +/- 44.2 ng/ml,
      respectively), whereas serum IGFBP-3 levels were lower in metastasized PC group
      than in BPH group (1,795.6 +/- 305.6 and 2,196.0 +/- 505.7 ng/ml; p = 0.005). In
      localized PC, serum IGFBP-3 levels (1,911.00 +/- 349.58 ng/ml) were similar to
      metastasized PC. There were significant correlations between serum IGFBP-3 and
      serum free PSA in three groups (r = -0.46, p = 0.02 for localized PC; r = -0.56,
      p = 0.01 for metastasized PC, and r = -0.31, p = 0.03 for BPH). CONCLUSION: These
      data reveal that serum IGF-I levels may not change either in localized or
      metastasized PC, and that decreased serum IGFBP-3 levels may be attributed to its
      proteolysis by PSA which is increased in PC.

PMID- 14730169
TI  - Retroperitoneal laparoscopic radical nephrectomy: experience of 23 cases.
AB  - INTRODUCTION: Retroperitoneal laparoscopic radical nephrectomy has recently been
      performed in several institutions for renal cancer. We report our experience with
      this type of operation and discuss the anatomy of perirenal fascial structures.
      PATIENTS AND METHODS: From July 2000 to May 2002, we performed retroperitoneal
      laparoscopic radical nephrectomy in 23 patients. We began this operation with
      longitudinal cutting of two layers of the posterior renal fasciae, and removed
      specimens without any fascial structure. RESULTS: Mean operative time was 203 min
      (range 129-314 min) with an average estimated blood loss of 113 ml (range 0-837
      ml). There was 1 patient who required open conversion due to uncontrollable
      hemorrhage, but no complication was observed. CONCLUSIONS: Retroperitoneal
      laparoscopic radical nephrectomy is a safe and reliable method when the anatomy
      of the perirenal fasciae is clearly understood. Long-term follow-up of patients
      undergoing this procedure is warranted to its effect on the prognosis of renal
      cancer.

PMID- 14730170
TI  - A new testis prosthesis material: polymethylmethacrylate.
AB  - INTRODUCTION: Silicone has been the standard prosthesis material for the last
      three decades but new materials are being searched because of the known
      disadvantages of silicone such as migration and high cost. We wanted to test in
      rats whether or not polymethylmethacrylate could be an alternative to silicone.
      MATERIALS AND METHODS: We prepared polymethylmethacrylate and silicone testis
      prostheses which were similar to testis size of rats. Eleven rats were implanted
      with polymethylmethacrylate, 11 others were implanted with a silicone prosthesis
      and sham operation was performed in 10 rats. Three months later the scrotums of
      the animals were removed with the prosthesis for a quantitative analysis of the
      chronic inflammation and fibrotic reaction and to measure the thickness of the
      capsule. RESULT: Rejection and infection were not observed in any of the
      prosthesis-implanted rats. Both prosthesis groups displayed increased
      vascularization, hemosiderin accumulation and fibrotic and hyalinized tissue
      formation that replaced the muscle. Chronic inflammation was measured and found
      to be higher in the polymethylmethacrylate group and the difference was not found
      to be significant. The average thicknesses of the capsules around the
      polymethylmethacrylate and silicone groups were found to be 58.4 and 46.8 microm,
      respectively, and that difference was not significant again. CONCLUSIONS: In the
      short term polymethylmethacrylate was equally well tolerated, but the low cost of
      polymethylmethacrylate made it more advantageous.

PMID- 14730171
TI  - Percutaneous pneumatic and laser lithotripsy as a possible therapeutic strategy
      for bilateral large calculi in a horseshoe kidney.
AB  - This report concerns a case of bilateral large calculi in a horseshoe kidney.
      Three sessions of percutaneous nephrolithotripsy for the calculi successfully
      disintegrated and removed the fragments without any complications. For complete
      stone removal we used pneumatic and laser lithotriptors which were passed,
      respectively, through a rigid nephroscope and a flexible pyeloscope. It is
      emphasized that the selection of the most suitable lithotriptor by taking their
      various features into account is important in endoscopic surgery for calculi
      which are likely to recur such as stones accompanied by infection or for
      anatomically anomalous kidneys such as horseshoe kidneys.

PMID- 14730172
TI  - Myofibroblastic inflammatory tumors of the bladder.
AB  - Bladder myofibroblastic inflammatory tumors are rare benign proliferative lesions
      that can simulate both urothelial and connective tissue malign neoplasms, making
      a preoperative diagnosis nearly impossible. Conservative treatment appears to be
      curative, even though local recurrences have been reported, and so malignancy
      should be ruled out above all by means of an accurate follow-up. Two cases are
      described, 1 of which with the longest follow-up period reported so far (8
      years).

PMID- 14730173
TI  - Primary non-Hodgkin's lymphoma of urinary bladder. Report of a case and review of
      the literature.
AB  - Primary extranodal lymphoma of the urinary bladder is a rare disorder that is
      diagnosed on the basis of histopathology and immunostaining. We report a case of
      diffuse B cell primary lymphoma of the urinary bladder and review the literature.

PMID- 14730174
TI  - Granulosa cell tumor of the contralateral testis in a man with a history of
      cryptorchism.
AB  - We report a case of adult-type testicular granulosa cell tumor in a 33-year-old
      man with a history of cryptorchism of the contralateral testis as well as Crohn's
      disease. The tumor was identified as a 1 x 1 x 1 cm mass on baseline ultrasound
      evaluation. CT evaluation of the patient revealed extensive mesenteric
      adenopathy, most likely secondary to his history of Crohn's disease.

PMID- 14730175
TI  - Colon perforation after percutaneous nephrolithotomy revisited.
AB  - Objective was to remind the reader of a rare but nevertheless serious
      complication of percutaneous nephrolithotomy (PCNL) which is further complicated
      by the lack of pre-operative and intra-operative warning signs. A patient
      underwent an apparently normal PCNL. Only just before removal of the nephrostomy
      tube, signs of colonic perforation became apparent. In spite of no clinical signs
      of sepsis or shock, the patient developed severe complications during and after
      the ensuing surgery. Every urologist, surgeon, or radiologist performing PCNL
      must be aware of the risk of an aberrant retrorenal colon loop, the perforation
      of which will most likely not be noticed during the procedure. Abdominal symptoms
      of a more general nature must lead to the active exclusion of this complication.
      If a CT scan has been performed pre-operatively for whatever reason, attention
      should be paid to the juxtarenal colon. Although a CT scan can exclude a
      retrorenal colon, such a procedure would exceed the needs and limitations of
      routine evaluation in all patients for PCNL.

PMID- 14730176
TI  - A case of acute pancreatitis presenting with electrocardiographic signs of acute
      myocardial infarction.
AB  - A 71-year-old man presented with left upper quadrant abdominal pain. Serial
      electrocardiograms (ECGs) demonstrated an evolving left bundle branch block, a
      sign of acute myocardial infarction (AMI). However, a coronary angiogram
      demonstrated minimal coronary artery disease, and serum troponin T was
      undetectable in serial serum measurements. Later, serum pancreatic enzyme levels
      were elevated and a computed tomography scan of the abdomen was consistent with
      pancreatitis. In patients presenting with acute pancreatitis and ECG changes
      suggesting AMI, measurement of serum troponin T concentrations can aid in
      differentiating ECG changes driven by acute pancreatitis from those of true
      myocardial ischemia or infarction.

PMID- 14730177
TI  - Legacy of a distinguished scientist: George E. Palade.

PMID- 14730178
TI  - Lactoferrin inhibits growth of malignant tumors of the head and neck.
AB  - Lactoferrin, a naturally occurring glycoprotein found in breast milk, has
      previously been shown to have antimicrobial properties and recently has been
      demonstrated to inhibit malignant tumor growth, presumably through
      immunomodulation. We hypothesized that intratumoral injection of human and murine
      recombinant lactoferrin would decrease the growth of malignant tumors in vivo.
      Using an orthotopic murine model for both squamous cell carcinoma and
      fibrosarcoma of the floor of the mouth, we administered lactoferrin directly into
      the tumors using variable dosing strategies. Additionally, we performed in vitro
      experiments to assess whether the effects of lactoferrin are due to direct
      cytotoxicity. Our results revealed growth inhibition of 50% (p=0.03)and 54%
      (p=0.01) as compared with controls for both human and murine tumor cells in
      immunodeficient and immunocompetent mice, respectively. There was a more dramatic
      effect in immunocompetent models which may identify immunomodulation as an
      important mechanism of action for lactoferrin. Support for immunomodulation as a
      possible mechanism was the lack of any difference between controls and the
      experimental groups in vitro. Lactoferrin proved effective in reducing malignant
      tumor growth in a murine model. These properties offer hope for its use as a
      primary or adjuvant chemotherapeutic agent. Further investigation focused on
      mechanism and delivery is needed.

PMID- 14730179
TI  - The effect of different 'pass-fail' criteria on the results of a newborn hearing
      screening program.
AB  - 'Pass' criteria in newborn hearing screening programs are important, since they
      affect the operating characteristics of the programs. In the present study, we
      intended to compare the results of two screening procedures, using different
      'pass' criteria, in two samples from the same pool of screened newborns. The
      subjects were divided into two study groups, screened consecutively during 6
      months. Testing and all procedures were exactly the same in both groups,
      differing only in the 'pass' criteria. In the first group a signal-to-noise ratio
      of at least 3 dB in the frequency bands of 1-2, 2-3 and 3-4 kHz was considered
      necessary for a 'pass', whereas a signal-to-noise ratio > or =6 dB was used in
      the second group, at the same frequency bands. During the period of the study, no
      other minor or major modification of the protocol was applied. The comparison of
      the screening predischarge results between the two groups showed no statistically
      significant differences in the 'pass-refer' results. Thus, it appears that the 3
      dB signal-to-noise ratio is as valid as the 6-dB criterion, and it may be
      confidently used, especially in settings where rescreening is not available.

PMID- 14730180
TI  - Magnetic resonance imaging of endolymphatic sac in acute low-tone sensorineural
      hearing loss without vertigo.
AB  - The etiology of acute low-tone sensorineural hearing loss (ALHL) may be
      associated with deteriorated function of the endolymphatic sac. Using magnetic
      resonance (MR) imaging on a 1.5-tesla MR system, we evaluated the frequency of
      visualization and contrast enhancement of the endolymphatic sac in 25 patients (9
      men and 16 women; age range 11-64 years) with ALHL and 21 control subjects. The
      present study demonstrated that the frequency of visualization and enhancement of
      the endolymphatic sac in patients with ALHL was not significantly higher than in
      control subjects.

PMID- 14730181
TI  - Management pathways and the surgical diagnosis of tuberculous lymphadenitis: can
      they be improved? The Bradford experience.
AB  - OBJECTIVE: To study the diagnostic pathway for tuberculous lymphadenitis from
      initial referral to the commencement of antituberculous therapy with the object
      of identifying potentially avoidable delays. DESIGN: Retrospective case series
      study. SETTING: District General Hospital, England, UK. SUBJECTS: Thirty-four
      patients with head and neck tuberculous lymphadenitis diagnosed by a positive
      histological specimen over the 3-year period 1998-2000. RESULTS: There were no
      clear pathways for referral and management. There were substantial variations in
      the management between different specialties and even sometimes within the same
      specialty. There was evidence of poor communication between various teams.
      CONCLUSIONS: The study shows that for the management of head and neck tuberculous
      lymphadenitis, there is a need for a 'hospital' or 'trust' approach. It also
      reinforces the arguments for a dedicated 'neck lump clinic' with easy access both
      from the general practitioners and from other specialties within the hospital and
      for a protocol for handling biopsy specimens from nodes.

PMID- 14730182
TI  - Changes of hair cell stereocilia and threshold shift after acoustic trauma in
      guinea pigs: comparison between inner and outer hair cells.
AB  - The vulnerability of inner hair cells (IHCs) and outer hair cells (OHCs) to
      acoustic overstimulation is still controversially discussed. The present study
      was undertaken to investigate the vulnerability of IHCs and OHCs and the relation
      between chronological changes of auditory threshold shifts and stereocilia
      damages on IHCs and OHCs in guinea pigs after moderate acoustic trauma, caused by
      a single continuous exposure to pink noise (20 Hz to 20 kHz) of around 106 +/- 2
      dB SPL for 44 h. Stereocilia changes and threshold shifts of auditory brainstem
      responses (ABR) were assessed at regular intervals after noise exposure for 9
      weeks. Scanning electron microscopy demonstrated the morphological changes of
      stereocilia as early as 1 day after noise exposure. The morphological changes
      included fused, bent, collapsed, and even missing stereocilia. These damages were
      more prominent on IHCs than on OHCs. The shift of ABR threshold was not parallel
      to the chronological change of the stereocilia on IHCs as well as OHCs. The
      elevation of the ABR threshold (40-60 dB SPL) was greatest on the 1st day after
      noise exposure, whereas the stereocilia showed the most damage 7 days after noise
      exposure. Combined with the results from previous studies, we conclude that
      moderate-level (around 105-110 dB) noise tends to induce more damage to the
      stereocilia of IHCs than of OHCs. Other damage (e.g., metabolic disturbance) than
      morphological damage of hair cell stereocilia may contribute partially to the
      hearing threshold shift induced by moderate acoustic overstimulation.

PMID- 14730183
TI  - Optimal specimen site for diagnosis of nasal T/NK cell lymphoma and treatment
      including bone marrow transplantation.
AB  - Nasal T/NK cell lymphoma is characterized by unrelenting progressive ulceration
      and necrosis of the nasal cavity and midline facial tissues. Computer tomography
      scans and biopsy specimens from 4 cases were studied in order to determine the
      optimal sampling site. Specimens should be from the lateral plate of the nasal
      cavity and the inferior turbinate. Bone marrow transplantation was performed in 2
      cases following chemotherapy and radiotherapy. The combination of chemotherapy,
      radiotherapy, and bone marrow transplantation has some ability to control the
      disease.

PMID- 14730184
TI  - Decreased measles virus-neutralizing activity in sera from otosclerotic patients.
AB  - HYPOTHESIS: Any kind of depressed systemic anti-measles reaction can lead to the
      induction of a local immune response in the inner ear and possibly to
      reactivation of bone turnover in this region. METHODS: Different dilutions of
      sera were tested for neutralizing activity against a constant viral
      concentration. The ability of measles virus to infect and replicate in the cell
      monolayer was detected by enumeration of living and growing cells with a colored
      reaction. RESULTS: Virus-neutralizing activity in the sera of patients with
      confirmed otosclerosis was significantly weaker than in that of healthy controls.
      When age- and sex-matched pairs were compared, the neutralizing activity in the
      healthy counterpart was higher in 5 cases. Nearly complete viral neutralization
      was achieved with samples containing inactivated complement and in IgG-containing
      fractions, but not in immunoglobulin-depleted samples. CONCLUSION: The present
      study is consistent with measles virus participation at least in the initiation
      of some cases of otosclerosis.

PMID- 14730185
TI  - Expression of aquaporins in the cochlea and endolymphatic sac of guinea pig.
AB  - It has been shown that the aquaporin (AQP) family forms membrane pores
      selectively permeable for water and some small solutes such as glycerol and urea,
      and thus plays important roles in regulating the fluid in many organs involved in
      fluid transport such as kidney, lung and brain. The aims of the present study
      were to investigate the cellular localization and its significance of aquaporins
      (AQPs) in various subregions of the cochlea and endolymphatic sac of guinea pig.
      The expression patterns of AQP1, 2, 3 and 4 were immunolabeled with the specific
      polyclonal rabbit antibodies against the rat AQP1, 2, 3 and 4. Our
      immunohistochemical examination showed that in the cochlea, AQP1, 3 and 4 were
      widely distributed in various locations including stria vascularis, spiral
      ligament, the organ of Corti and spiral ganglion in the similar patterns except
      that AQP3 in the stria vascularis was lightly weaker than AQP1 and AQP4. AQP2 was
      labeled only in Reissner's membrane. In the endolymphatic sac, AQP1, AQP3 and
      AQP4 were strongly expressed in the epithelial cells and subepithelial cells
      similarly with the exception that AQP3 was lightly weaker than AQP1 and AQP4. No
      AQP2 immunoreactivity was detected in the endolymphatic sac. Theses results
      suggest that different members of the AQP family in the labyrinth may work in
      concert to regulate endolymph and to maintain homeostasis in the inner ear.

PMID- 14730186
TI  - Benign paroxysmal positioning vertigo: diagnosis and therapy using video
      oculographic control.
AB  - In this prospective study, 82 patients (40 males, 42 females, aged between 15 and
      80 years) with benign paroxysmal positioning vertigo (BPPV) were treated with
      different positioning manoeuvres using video-oculographic control. The maximum
      age for females and males was 31 and 40 years respectively. After an interview
      about the special history related to vertigo imbalance symptoms and using video
      oculographic control, we diagnosed 79 patients with BPPV of the posterior
      semicircular canal and 3 of the horizontal semicircular canal. The Dix-Hallpike
      and Cawthorne manoeuvres were used for the diagnosis of BPPV of the posterior
      semicircular canal and the McClure manoeuvre for the diagnosis of BPPV of the
      horizontal semicircular canal. 72% of the patients had an idiopathic BPPV and
      12.2% were post-traumatic. 3.7% had BPPV after ear surgery and 2.4% were
      pregnant. 39 patients with posterior BPPV were treated with Semont's manoeuvre
      and 40 with Epley's. The 3 patients with horizontal BPPV were treated with
      Baloh's manoeuvre. More than half of the patients (52.5%) were free of symptoms
      after one session of Epley's manoeuvre and all of them after four sessions. 51.3%
      had no further symptoms after one session of Semont's manoeuvre and all of them
      after four sessions. These results, in agreement with the literature, show that
      the success rate of Semont's and Epley's manoeuvres is approximately the same.
      Video-oculographic control is helpful for the diagnosis and for the registration
      of the eye movements during the therapeutic manoeuvres.

PMID- 14730187
TI  - Benign mixed tumor of the lacrimal gland. Clinical diagnosis and surgical
      management.
AB  - The accurate clinical diagnosis of benign mixed tumors of the lacrimal gland is
      important for the proper therapeutic management. We present an adult case with a
      benign mixed tumor of the orbital lobe of the lacrimal gland, 8 years after
      periorbital blunt injury. The tumor lesion was diagnosed later in the persisting
      traumatic tumefaction region. Clinical examination, ultrasonography and MRI
      revealed a soft-tissue mass with high density and peripheral enhancement over the
      superior lateral portion of the right eye with expansion to and invasion of the
      orbital roof and lateral wall. Lateral orbitotomy was performed to resect the
      tumor. Histopathology disclosed a pleomorphic adenoma of the orbital lobe of the
      lacrimal gland. Pleomorphic adenomas of the lacrimal gland are seen rarely. The
      awareness of the clinical and diagnostic features of benign mixed tumors of the
      orbital lobe should help to avoid complications arising from an incisional biopsy
      or incomplete tumor resection.

PMID- 14730188
TI  - Recurrent ceruminous adenocarcinoma of the external auditory canal.
AB  - Ceruminous adenocarcinoma is a rare malignant neoplasm of the glandular
      structures of the external auditory canal. The true incidence and behavior of
      these rare tumors are still unclear due to confusing terminology, classification
      and histological definitions. Therefore, the ENT surgeon faces major difficulties
      in choosing the method of management--conservative or more radical surgery--with
      the addition or not of radiotherapy. We report a 57-year-old male patient with a
      recurrence of a previously excised (maybe partially) and irradiated ceruminous
      adenocarcinoma of the right external auditory canal. Aggressive surgery was
      considered as the treatment of choice. However, the patient refused this approach
      and, as a consequence, a conservative excision was performed but with
      histologically confirmed healthy margins. To our surprise, the patient showed an
      excellent response and he is disease free 3 years following the last operation.
      Although recurrences usually occur within months after inadequate management,
      some may happen even 7 years post treatment. Therefore, routine long-term follow
      up was advised.

PMID- 14730189
TI  - Refractory rhinosinusitis complicating immunosuppression: application of N
      chlorotaurine, a novel endogenous antiseptic agent.
AB  - Severe infections are a frequent complication in immunosuppression following
      transplantations. In the case reported here, a heart-transplanted patient was
      treated for refractory rhinosinusitis with a combination of sinus surgery and
      rinsing with N-chlorotaurine (NCT). The daily rinse was well tolerated and
      effective. The combination of functional endonasal sinus surgery and topical
      treatment with NCT appeared effective and well tolerated in antibiotic-resistant
      sinusitis under immunosuppression.

PMID- 14730190
TI  - A case report of unilateral hypoglossal neuroparalysis resulting from horizontal
      subluxation in the atlanto-occipital joint due to rheumatoid arthritis.
AB  - We experienced a case of unilateral hypoglossal neuroparalysis, in which the
      right hypoglossal nerve was compressed by horizontal subluxation in the atlanto
      occipital joint, due to rheumatoid arthritis. This report represents a very rare
      case of unilateral hypoglossal neuroparalysis, in which diagnostic imaging of CT
      with multiple cross-sectional images (three-dimensional CT) was quite useful for
      the identification of compression by horizontal subluxation.

PMID- 14730191
TI  - Ancient schwannoma of the true vocal cord.
AB  - Ancient schwannomas are benign nerve origin neoplasms that may cause difficulties
      in the differential diagnosis with other benign or malignant tumors. They usually
      occur in the head and neck region (epiglottis, arytenoepiglottic fold, false
      vocal cord). Involvement of the true vocal cords is extremely rare (less than 10
      cases have ever been reported in the English literature--mainly in women). The
      present case describes a 27-year-old man who presented with a 2-year history of
      hoarseness. Indirect laryngoscopy showed a small polypoid mass in the middle of
      the left vocal cord. During microlaryngoscopy under general anesthesia, the
      polypoidal mass was removed and sent for histology. Immunohistochemistry and
      detailed histological examination revealed an ancient schwannoma. The present
      case in a male patient aims to increase awareness of the possibility that these
      tumors may also exist in the true vocal cords mimicking other more frequent
      lesions.

PMID- 14730192
TI  - Association study of onset age, attempted suicide, aggressive behavior, and
      schizophrenia with a serotonin 1B receptor (A-161T) genetic polymorphism.
AB  - Located on the presynaptic and postsynaptic terminals of serotonergic neurons,
      serotonin 1B receptors (5-HT1B) are involved in the modulation of serotonergic
      activity. The implications of 5-HT1B study of animal models of schizophrenia and
      antipsychotic activity involving defective sensory processes suggest that this
      receptor may be involved in the pathogenesis of schizophrenic disorders. In a
      population-based association study, we tested the hypothesis that the allelic
      variant, A-161T, of the 5-HT1B gene confers susceptibility to schizophrenic
      disorders and is associated with age of onset, aggressive behavior and attempted
      suicide. We genotyped the A-161T polymorphism in 110 patients with schizophrenic
      disorders and in 215 normal controls. No association was demonstrated between 5
      HT1B genotype or allele frequencies and schizophrenic disorders, except for a
      trend for later age at disease onset in A/A homozygote schizophrenics in
      comparison with A/T heterozygote patients (p = 0.071). No significant difference
      in genotype distribution was determined comparing patients with and without
      aggressive behavior, and those with and without a history of suicide attempt.
      These findings suggest that the investigated 5-HT1B genetic polymorphism does not
      play a major role in the pathogenesis of schizophrenic disorders.

PMID- 14730193
TI  - Altered habituation in the auditory cortex in a subgroup of depressed patients by
      functional magnetic resonance imaging.
AB  - The aim of this study was to measure and quantify habituation effects to auditory
      stimulation within the auditory cortex of 11 depressed patients with major
      depressive disorder compared to 11 healthy subjects. Habituation was visualized
      by functional magnetic resonance imaging (fMRI) employing a block design
      (repeated stimulation with sine tones). A subgroup of patients (n = 5) presented
      the following abnormal habituation fMRI pattern: significantly lower activation
      after the first stimulation block (p = 0.05), missing characteristic signal decay
      to repeated acoustic stimulation and a marked undershoot after each stimulation
      block. This abnormal pattern may indicate functional deficits in auditory
      processing occurring with depression, but our results need be confirmed in a
      larger, more homogeneous patient group. This paradigm may be a useful tool for
      assessing cortical dysfunction in mood disorders.

PMID- 14730194
TI  - Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms
      with Alzheimer's disease and age of onset.
AB  - Because of a decrease in central brain-derived neurotrophic factor (BDNF) levels
      in Alzheimer's disease (AD) and the important role of BDNF in neuronal survival,
      BDNF may represent a candidate gene conferring susceptibility to AD. Recently, a
      functional BDNF Val66Met polymorphism has been associated with AD in an Italian
      population. In the present study, we investigated a possible role of this BDNF
      polymorphism in the susceptibility of AD or AD onset in a Chinese population.
      Comparing AD patients and controls, the distribution of the BDNF genotypes and
      alleles did not differ significantly. The onset age was not significantly
      different comparing the three BDNF genotype groups. Our negative findings suggest
      that it is unlikely that the BDNF Val66Met polymorphism plays a major role in the
      pathogenesis of AD in the Chinese population and do not support previous findings
      that homozygosity for the 66Val allele confers an increased risk for AD. Further
      studies with genetic variations in BDNF relating either to AD-associated
      depression or to the AD treatment response are suggested.

PMID- 14730195
TI  - Association study of a brain-derived neurotrophic factor (BDNF) Val66Met
      polymorphism and personality trait and intelligence in healthy young females.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the nerve-growth-factor
      family, plays an important role in neuronal survival and development, and it can
      modulate serotonergic activity. Further, BDNF has been implicated in the
      expression of personality traits and in cognitive function. We tested the
      associations between functional BDNF Val66Met genetic variants, and personality
      trait and intelligence in a cohort of 114 healthy young Chinese females. Subjects
      with the Val/Val genotype had a significantly higher mean performance IQ than
      Val/Met carriers, especially for the Object Assembly subtest. No significant
      association was demonstrated for the BDNF polymorphism and any of the
      Tridimensional Personality Questionnaire personality-factor scores, including
      harm avoidance. These results suggest that genetic variants of the BDNF gene may
      play a role in specific cognitive functions, but not in overall intelligence. In
      contrast to a recent report, however, this polymorphism does not appear to be
      associated with the neuroticism-related personality trait.

PMID- 14730196
TI  - The influence of parturition on the level and synthesis of sulfated and free
      neurosteroids in rats.
AB  - Alterations in neurosteroid levels may play a role in affective disorders
      including those related to changes in the levels of ovarian steroids. The effects
      of pregnancy and delivery on circulatory and brain levels of
      dehydroepiandrosterone (DHEA), pregnenolone (PN), their sulfate esters and the
      enzymatic activities of sulfatase and sulfotransferase were examined in rats. Our
      findings indicate an increase, not reflected in the brain cortex, in serum DHEA
      levels, at the end of pregnancy with a partial decrease following delivery. DHEA
      sulfate levels in the cortex and PN levels in both serum and cortex decreased
      following delivery with no changes in its sulfated form. Sulfatase levels were
      high both before and after delivery with no changes noted in sulfotransferase
      levels, compared to controls. We speculate that changes in the level or ratio of
      sulfated and free neurosteroids may play a role in postpartum behavioral
      disorders due to their antagonistic GABA(A) modulatory effect.

PMID- 14730197
TI  - Psychobiological aspects of somatoform disorders: contributions of monoaminergic
      transmitter systems.
AB  - OBJECTIVE: To evaluate the possible biological aspects of 'unexplained physical
      symptoms', this study examined serotonergic and noradrenergic monoamino acids in
      somatoform disorders and/or depression. METHODS: Blood samples of 150 subjects
      from 4 groups (somatization syndrome; depression; depression and somatization;
      controls) were analyzed for amino acids contributing to the serotonergic and
      noradrenergic system and peripheral muscle energy balance (tryptophan, valine,
      leucine, isoleucine, phenylalanine and tyrosine). RESULTS: Tryptophan, branched
      chain amino acids and other serotonergic amino acids were decreased in patients
      with somatoform symptoms, even when no depression was present. CONCLUSIONS: We
      conclude that serotonergic amino acids are biological correlates of multiple
      unexplained symptoms. Ways of action do not only involve brain mechanisms, but
      also energy metabolism in peripheral muscles.

PMID- 14730198
TI  - Self-organizing neural network analyses of cardiac data in depression.
AB  - OBJECTIVE: To determine if an unsupervised self-organizing neural network could
      create a clinically meaningful distinction of 'depression' versus 'no depression'
      based on cardiac time-series data. DESIGN: A self-organizing map (SOM) was used
      to separate the time-series of 84 subjects into groups based on characteristics
      of the data alone. MATERIALS AND METHODS: Analyses included natural log
      transformations and two types of filtering to enhance characteristics of the data
      as well as classifications of unprocessed data. A Pearson chi(2) analysis was
      performed to determine if the SOM groups bore any relation to the binary clinical
      groups. RESULTS: Overall correct SOM classifications ranged from 54 to 70.2% with
      two classifications being clinically meaningful. CONCLUSIONS: SOM classifications
      of cardiac time-series data with enhanced ultradian variations and cardiac data
      recorded around the interval when a person was in bed were useful in
      differentiating clinically meaningful subgroups with and without depression.

PMID- 14730199
TI  - Association between major depressive disorder and the -1438A/G polymorphism of
      the serotonin 2A receptor gene.
AB  - This study investigated the possible effect of the -1438A/G single-nucleotide
      polymorphism in the promoter region of the serotonin 2A receptor (5-HTR2A) gene
      on major depressive disorder (MDD) in a Korean population. This polymorphism was
      analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a
      case-control design, which revealed a significant difference in the genotype
      distributions (chi(2) = 10.78, d.f. = 2, p = 0.005). The frequency of the -1438G
      allele was also much higher in MDD patients than in normal controls (chi(2) =
      7.20, p = 0.007; OR = 1.52, 95% CI 1.12-2.06). We also found significantly more
      carriers of the G allele (GG+AG genotypes) in MDD patients than in normal
      controls (chi(2) = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40-4.32). Our results
      support the hypothesis that the -1438A/G polymorphism of the promoter region of
      the 5-HTR2A gene is associated with MDD patients in a Korean population.

PMID- 14730200
TI  - Neurobiological and psychological correlates of suicidal attempts and thoughts of
      death in patients with major depression.
AB  - Suicide is a major problem for psychiatry. Depression is the most common mental
      disorder related to suicidal behavior. The present study aimed at investigating
      the relationship between the symptomatology related to death, dying, and suicide
      and neurobiological factors in depressed patients. Fifty patients aged 21-60
      years suffering from major depression were investigated. Schedules for Clinical
      Assessment in Neuropsychiatry version 2.0 and the International Personality
      Disorder Examination were used to assist the clinical diagnosis. The psychometric
      assessment included the Hamilton Depression Rating Scale, the Hamilton Anxiety
      Scale, the 1965 and 1971 Newcastle Depression Diagnostic Scales, the Diagnostic
      Melancholia Scale, the General Assessment of Functioning Scale, and the
      Personality Deviance Scale. Psychophysiological methods included electro
      oculogram, flash electroretinogram under photopic and scotopic conditions, and
      pattern-reversal visual evoked potentials. Biological markers included the 1-mg
      dexamethasone suppression test, the 30-mg dexfenfluramine challenge test, and
      brain (99m)Tc-HMPAO SPECT. Statistical analysis included one-, two-, and three
      way Manova and Mancova and the Scheffe test as post hoc test. Patients without
      thoughts of death had higher self-confidence levels and less overdependency on
      others and intropunitiveness. The suicidal patients had a significantly prolonged
      pattern-reversal visual evoked potential latency in comparison with the other
      patients. The findings of this were related to the status of the patient at the
      time of the interview but not to his/her history. They also provide
      neurobiological data to support the need for a combined presence of self-directed
      aggression and a higher arousal level or disinhibition of self-directed
      aggressive thoughts in order for a patient to become suicidal. Further study is
      needed to test whether psychophysiological methods, which are noninvasive and
      easy to perform, are of value in the therapeutic planning and monitoring of
      responses.

PMID- 14730201
TI  - Neointimal hyperplasia after stenting in a human mammary artery organ culture.
AB  - Although the use of stents has limited the incidence of restenosis, in-stent
      restenosis remains an important problem. In-stent restenosis is the result of a
      healing process that induced neointimal hyperplasia through mechanisms that are
      still not understood. The aim of this study was to analyze the histological
      consequences of the healing process following stent implantation. Internal
      mammary arteries from atheroslerotic patients undergoing coronary artery bypass
      surgery were stented and maintained in culture for 0-28 days. Stent implantation
      after predilatation induced an extensive loss of endothelial cells whereas direct
      stenting preserved endothelium between the struts. Morphometric analysis shows
      that stent placement induced neointimal thickening. Smooth muscle alpha-actin
      labeling indicates that neo-intimal formation was mainly due to proliferation and
      migration of smooth muscle cells. Smooth muscle cell proliferation, assessed by
      MIB-1 staining, was maximal at day 14 after stent insertion. Human mammary artery
      organ culture thus provides valuable information on histological consequences of
      stent implantation with or without predilatation regarding endothelial cell
      disappearance and neointimal hyperplasia. These data also demonstrate that
      neointimal thickening induced by stent implantation comprises an intrinsic
      component resulting from the vessel wall response to stent insertion and suggest
      that blood factors could play an amplifying but not necessary role.

PMID- 14730202
TI  - Two-photon microscopy for imaging of the (atherosclerotic) vascular wall: a proof
      of concept study.
AB  - BACKGROUND: Understanding atherogenesis will benefit significantly from
      simultaneous imaging, both ex vivo and in vivo, of structural and functional
      information at the (sub)cellular level within intact arteries. Due to limited
      penetration depth and loss of resolution with depth, intravital and confocal
      fluorescence microscopy are not suitable to study (sub)cellular details in
      arteries with wall thicknesses above 50 microm. METHODS: Using two-photon laser
      scanning microscopy (TPLSM), which combines 3D resolution and large penetration
      depth, we imaged mouse carotid arteries. RESULTS: In thin slices, (sub)cellular
      structures identified using histochemical techniques could also be identified
      using TPLSM. Ex vivo, structural experiments on intact atherosclerotic arteries
      of Apo-E(-/-) mice demonstrated that in contrast to confocal or wide-field
      microscopy, TPLSM can be used to visualize (sub) cellular structural details of
      atherosclerotic plaques. In vivo, pilot experiments were carried out on healthy
      arteries of wild-type C57BL6 and atherosclerotic arteries of Apo-E(-/-) mice. As
      an example of functional measurements, we visualized fluorescently labeled
      leukocytes in vivo in the lumen. Additionally, detailed morphological information
      of vessel wall and atherosclerotic plaque was obtained after topical staining.
      CONCLUSIONS: Thus, TPLSM potentially allows combined functional and structural
      studies and can therefore be eminently suitable for investigating structure
      function relationships at the cellular level in atherogenesis in the mouse.

PMID- 14730203
TI  - Role of reactive oxygen species-sensitive extracellular signal-regulated kinase
      pathway in angiotensin II-induced endothelin-1 gene expression in vascular
      endothelial cells.
AB  - BACKGROUND: Circulating angiotensin II (Ang II) increases vascular endothelin-1
      (ET-1) tissue levels, which in turn mediate a major part of Ang II-stimulated
      vascular growth and hypertension in vivo. Ang II also stimulates the generation
      of reactive oxygen species (ROS) within vascular endothelial cells. However,
      whether ROS are involved in Ang II-induced ET-1 gene expression, and the related
      intracellular mechanisms occurring within vascular endothelial cells remain
      unclear. METHODS: Cultured endothelial cells were stimulated with Ang II, and the
      thus elicited ET-1 gene expression was examined by Northern blotting and a
      promoter activity assay. Antioxidant pretreatment of endothelial cells was
      performed prior to Ang II-induced extracellular signal-regulated kinase (ERK)
      phosphorylation in order to elucidate the redox-sensitive pathway for ET-1 gene
      expression. RESULTS: The ET-1 gene was induced with Ang II, which was inhibited
      with Ang II type 1 receptor antagonist (irbesartan). Ang II-enhanced
      intracellular ROS levels were inhibited by irbesartan and several antioxidants,
      and antioxidants also suppressed Ang II-induced ET-1 gene expression. Further,
      Ang II-activated ERK phosphorylation was also significantly inhibited by certain
      antioxidants. An ERK inhibitor, U0126, inhibited Ang II-induced ET-1 expression
      completely. Cotransfection of the dominant negative mutant of Ras, Raf and MEK1
      (ERK kinase) attenuated the Ang II-enhanced ET-1 promoter activity, suggesting
      that the Ras/Raf/ERK pathway is required for Ang II-induced ET-1 gene expression.
      Ang II-induced activator protein-1 (AP-1) reporter activities were inhibited by
      antioxidants. Moreover, mutational analysis of the ET-1 gene promoter showed that
      the AP-1 binding site was an important CIS element in Ang II-induced ET-1 gene
      expression. CONCLUSIONS: Our data suggest that ROS are involved in Ang II-induced
      ET-1 gene expression within endothelial cells. The redox-sensitive ERK-mediated
      AP-1 transcriptional pathway plays an important role in Ang II-induced ET-1 gene
      expression.

PMID- 14730204
TI  - Human phenotypes and animal knockout models of genetic autonomic disorders.
AB  - Norepinephrine (NE) is a crucial neurotransmitter involved in autonomic
      regulation of blood pressure. Dopamine beta-hydroxylase (DBH), the norepinephrine
      transporter (NET), and the vesicular monoamine transporter subtype 2 catalyze
      intracellular NE biosynthesis, NE reuptake from the synapse, and vesicular
      transport, respectively. Genetic disorders in humans have been identified that
      render DBH, and the NET dysfunctional and result in cardiovascular and
      neurological abnormalities. Vesicular monoamine transporter subtype 2 (VMAT2)
      activity protects against neurotoxins, and reduced VMAT2 expression is implicated
      in drug addiction. Further investigation of the consequences of these genetic
      abnormalities has been achieved by the construction of mice strains deficient in
      the genes encoding DBH, NET, and VMAT2.

PMID- 14730205
TI  - The inhibitory effect of trilinolein on norepinephrine-induced beta-myosin heavy
      chain promoter activity, reactive oxygen species generation, and extracellular
      signal-regulated kinase phosphorylation in neonatal rat cardiomyocytes.
AB  - The myocardial protective effects of trilinolein, isolated from the traditional
      Chinese herb Sanchi (Panax notoginseng), are thought to be related to its
      antioxidant activity. However, the intracellular mechanism underlying the
      protective effect of trilinolein in the heart remains unclear. In the present
      study, we investigated the effect of trilinolein on norepinephrine (NE)-induced
      protein synthesis in cardiomyocytes. Cultured neonatal rat cardiomyocytes were
      stimulated with NE, then protein content, [(3)H]-leucine incorporation, and beta
      myosin heavy chain (beta-MyHC) promoter activity were examined. The effect of
      trilinolein on NE-induced intracellular reactive oxygen species (ROS) generation
      was measured with a redox- sensitive fluorescent dye (2',7'-dichlorofluorescin
      diacetate) and extracellular signal-regulated kinase (ERK) phosphorylation by
      Western blotting. Trilinolein inhibited NE-increased protein synthesis, beta-MyHC
      promoter activity, and intracellular ROS. Both trilinolein and the antioxidant, N
      acetyl-cysteine, decreased NE- and H(2)O(2)-induced protein synthesis, beta-MyHC
      promoter activity, and ERK phosphorylation. These data indicate that trilinolein
      inhibits NE-induced protein synthesis via attenuation of ROS generation in
      cardiomyocytes.

PMID- 14730206
TI  - Involvement of the antiplatelet activity of magnesium sulfate in suppression of
      protein kinase C and the Na+/H+ exchanger.
AB  - Magnesium sulfate is widely used to prevent seizures in pregnant women with
      hypertension. The aim of this study was to examine the inhibitory mechanisms of
      magnesium sulfate in platelet aggregation in vitro. In this study, magnesium
      sulfate concentration-dependently (0.6-3.0 mM) inhibited platelet aggregation in
      human platelets stimulated by agonists. Magnesium sulfate (1.5 and 3.0 mM) also
      concentration-dependently inhibited phosphoinositide breakdown and intracellular
      Ca+2 mobilization in human platelets stimulated by thrombin. Rapid
      phosphorylation of a platelet protein of M(r) 47,000 (P47), a marker of protein
      kinase C activation, was triggered by phorbol-12-13-dibutyrate (PDBu, 50 nM).
      This phosphorylation was markedly inhibited by magnesium sulfate (3.0 mM).
      Magnesium sulfate (1.5 and 3.0 mM) further inhibited PDBu-stimulated platelet
      aggregation in human platelets. The thrombin-evoked increase in pHi was markedly
      inhibited in the presence of magnesium sulfate (3.0 mM). In conclusion, these
      results indicate that the antiplatelet activity of magnesium sulfate may be
      involved in the following two pathways: (1) Magnesium sulfate may inhibit the
      activation of protein kinase C, followed by inhibition of phosphoinositide
      breakdown and intracellular Ca+2 mobilization, thereby leading to inhibition of
      the phosphorylation of P47. (2) On the other hand, magnesium sulfate inhibits the
      Na+/H+ exchanger, leading to reduced intracellular Ca+2 mobilization, and
      ultimately to inhibition of platelet aggregation and the ATP-release reaction.

PMID- 14730207
TI  - 17beta-estradiol downregulates angiotensin-II-induced endothelin-1 gene
      expression in rat aortic smooth muscle cells.
AB  - It is well documented that 17beta-estradiol (E(2)) exerts a cardiovascular
      protective effect. A possible role of E(2) in the regulation of endothelin-1 (ET
      1) production has been reported. However, the complex mechanisms by which E(2)
      inhibits ET-1 expression are not completely understood. The aims of this study
      were to examine whether E(2) may alter angiotensin II (Ang II)-induced cell
      proliferation and ET-1 gene expression and to identify the putative underlying
      signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth
      muscle cells were preincubated with E(2), then stimulated with Ang II, and
      [(3)H]thymidine incorporation and ET-1 gene expression were examined. The effect
      of E(2) on Ang-II-induced extracellular signal-regulated kinase (ERK)
      phosphorylation was tested to elucidate the intracellular mechanism of E(2) in
      proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was
      inhibited with E(2) (1- 100 nM). E(2), but not 17alpha-estradiol, inhibited the
      Ang-II-induced ET-1 gene expression as revealed by Northern blotting and promoter
      activity assay. This effect was prevented by coincubation with the estrogen
      receptor antagonist ICI 182,780 (1 microM). E(2) also inhibited Ang-II-increased
      intracellular reactive oxygen species (ROS) as measured by a redox-sensitive
      fluorescent dye, 2',7'-dichlorofluorescin diacetate, and ERK phosphorylation.
      Furthermore, E(2) and antioxidants, such as N-acetyl cysteine and diphenylene
      iodonium, decreased Ang-II-induced cell proliferation, ET-1 promoter activity, ET
      1 mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity.
      In summary, our results suggest that E(2) inhibits Ang-II-induced cell
      proliferation and ET-1 gene expression, partially by interfering with the ERK
      pathway via attenuation of ROS generation. Thus, this study provides important
      new insight regarding the molecular pathways that may contribute to the proposed
      beneficial effects of estrogen on the cardiovascular system.

PMID- 14730208
TI  - Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor
      degeneration in RCS rats.
AB  - Ciliary neurotrophic factor (CNTF) is known as an important factor in the
      regulation of retinal cell growth. We used both recombinant CNTF and an
      adenovirus carrying the CNTF gene to regulate retinal photoreceptor expression in
      a retinal degenerative animal, Royal College of Surgeons (RCS) rats. Cells in the
      outer nuclear layer of the retinae from recombinant-CNTF-treated, adenoviral-CNTF
      treated, saline-operated, and contralateral untreated preparations were examined
      for those exhibiting CNTF photoreceptor protective effects. Cell apoptosis in the
      outer nuclear layer of the retinae was also detected. It was found that CNTF had
      a potent effect on delaying the photoreceptor degeneration process in RCS rats.
      Furthermore, adenovirus CNTF gene transfer was proven to be better at rescuing
      photoreceptors than that when using recombinant CNTF, since adenoviral CNTF
      prolonged the photoreceptor protection effect. The function of the photoreceptors
      was also examined by taking electroretinograms of different animals. Adenoviral
      CNTF-treated eyes showed better retinal function than did the contralateral
      control eyes. This study indicates that adenoviral CNTF effectively rescues
      degenerating photoreceptors in RCS rats.

PMID- 14730209
TI  - Neutrophil elastase induces IL-8 synthesis by lung epithelial cells via the
      mitogen-activated protein kinase pathway.
AB  - The sequestration of neutrophils in the lung and the release of proinflammatory
      mediators, including neutrophil elastase, are responsible for sepsis-induced
      microvascular permeability and alveolar epithelial cell damage. To assess the
      underlying mechanism, human neutrophil elastase (0.01-0.5 microg/ml) was added to
      cultured A549 epithelial cells in the presence or absence of inhibitors. IL-8 was
      analyzed by ELISA or by RT-PCR to measure the IL-8 synthesis capacity. Mitogen
      activated protein kinase (MAPK) activity was detected by Western blot analysis.
      Neutrophil elastase dose-dependently increased IL-8 release from cultured A549
      epithelial cells. Pretreatment with a specific elastase inhibitor, elastase
      inhibitor II (at 0.5, 5, and 50 microg/ml), dose-dependently inhibited neutrophil
      elastase-induced IL-8 release. The activities of MAPK, p38, and extracellular
      signal-regulated kinase (ERK) were upregulated by neutrophil elastase. Nuclear
      transcriptional factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) were
      also activated. These responses were significantly inhibited by elastase
      inhibitor II. A specific inhibitor of p38 MAPK (SB203580) and an NF-kappaB
      inhibitor (pyrrolidine dithiocarbamate), but not an ERK inhibitor (PD 98059),
      significantly inhibited neutrophil elastase-induced IL-8 release and mRNA
      expression. The specific tyrosine kinase inhibitor, genistein, and the protein
      kinase C (PKC) inhibitor, Ro 31-8220, also inhibited IL-8 release and mRNA
      expression as well as p38 and NF-kappaB activation. There was no significant
      effect by the protein kinase A inhibitor, H-89, on neutrophil elastase-induced IL
      8 synthesis or p38 MAPK activation. Our results indicate that neutrophil elastase
      activates p38 MAPK which upregulates NF-kappaB and AP-1 activities, thus inducing
      IL-8 mRNA expression and protein synthesis. Tyrosine kinase and PKC are
      implicated in neutrophil elastase activation of the MAPK pathway.

PMID- 14730210
TI  - Myeloperoxidase gene variation and coronary flow reserve in young healthy men.
AB  - Chronic inflammation may lead to endothelial dysfunction, which manifests as an
      impaired coronary reactivity. Impairment in coronary flow reserve (CFR),
      preceding the clinical symptoms of coronary artery disease, can be measured
      noninvasively by positron emission tomography. Myeloperoxidase (MPO) is an
      oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene
      has a promoter polymorphism (-463G/A) which affects gene transcription. Whether
      these variants associate with coronary artery function is not known. Myocardial
      blood flow at rest and during adenosine-induced hyperemia was assessed in 49
      healthy young men with normal or slightly elevated serum total cholesterol. These
      subjects were divided into high (G/G) and low (A/G, A/A) MPO expression groups
      and effect of MPO genotype on myocardial blood flow was evaluated. We found a
      significant difference between MPO genotypes in CFR after adjusting for age, body
      mass index, smoking and family history of cardiovascular disease (p = 0.019). Men
      with G/G genotype had 18.1% lower CFR than subjects with low-expression genotypes
      (A/G and A/A). This was due to an 11.5% lower adenosine-stimulated flow of the
      G/G genotype carriers (p = 0.049). These findings provide evidence that MPO
      polymorphism is associated with coronary artery reactivity. However, the number
      of individuals investigated was low and our observation should be confirmed by a
      larger number of subjects.

PMID- 14730211
TI  - Biological significance of chromosomal imbalance aberrations in gastrointestinal
      stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. Current criteria for the diagnosis of malignant GISTs
      do not always reliably predict patient outcomes. In order to search for genetic
      markers with prognostic potential, chromosomal imbalance aberrations (CIAs) were
      analyzed in 28 subjects with GIST using comparative genomic hybridization and
      correlated with clinicopathological features. Except for a small rectal tumor,
      CIAs were identified in all GISTs, including 14 from the stomach, 11 from the
      small intestine, 1 from the esophagus, and 1 from the rectum. Losses were more
      common than gains. The median number of CIAs in high-risk GISTs was significantly
      higher than that in low-risk GISTs (5.60 +/- 2.59 vs. 3.38 +/- 2.55; p < 0.05),
      especially for losses (4.60 +/- 1.84 vs. 2.63 +/- 2.13; p < 0.01). Loss of 14q
      was the most common CIA in both low-risk and high-risk GISTs, and can be regarded
      as an early event of GIST development. Losses of 1p and 15q were also very
      common, often coexisting, and were slightly more frequent in high-risk GISTs than
      in low-risk GISTs. Other recurrent CIAs, including losses of 10q, 13q, 15q, 18q,
      and 22q and gains of 5p, 12q, 17q, and 20q were relatively less common in this
      series. Among these CIAs, losses of 13q, 10q (with minimal overlapping on q11
      q22), and 22q were most likely the chromosomal loci potentially harboring the
      tumor suppressor gene(s) which may be related to early recurrence and/or
      metastasis during malignant transformation of GISTs.

PMID- 14730212
TI  - Activation of RNA polymerase I transcription by hepatitis C virus core protein.
AB  - The hepatitis C virus (HCV) core protein has been implicated in the
      transregulation of various RNA polymerase (Pol) II dependent genes as well as in
      the control of cellular growth and proliferation. In this study, we show that the
      core protein, whether individually expressed or produced as part of the HCV viral
      polyprotein, is the only viral product that has the potential to activate RNA Pol
      I transcription. Deletion analysis demonstrated that the fragment containing the
      N-terminal 1-156 residues, but not the 1-122 residues, of HCV core protein
      confers the same level of transactivation activity as the full-length protein.
      Moreover, the integrity of the Ser(116) and Arg(117) residues of HCV core protein
      was found to be critical for its transregulatory functions. We used DNA affinity
      chromatography to analyze the human ribosomal RNA promoter associated
      transcription machinery, and the results indicated that recruitment of the
      upstream binding factor and RNA Pol I to the ribosomal RNA promoter is enhanced
      in the presence of HCV core protein. Additionally, the HCV core protein mediated
      activation of ribosomal RNA transcription is accompanied by the
      hyperphosphorylation of upstream binding factor on serine residues, but not on
      threonine residues. Moreover, HCV core protein is present within the RNA Pol I
      multiprotein complex, indicating its direct involvement in facilitating the
      formation of a functional transcription complex. Protein-protein interaction
      studies further indicated that HCV core protein can associate with the
      selectivity factor (SL1) via direct contact with a specific component, TATA
      binding protein (TBP). Additionally, the HCV core protein in cooperation with TBP
      is able to activate RNA Pol II and Pol III mediated transcription, in addition to
      RNA Pol I transcription. Thus, the results of this study suggest that HCV has
      evolved a mechanism to deregulate all three nuclear transcription systems, partly
      through targeting of the common transcription factor, TBP. Notably, the ability
      of the HCV core protein to upregulate RNA Pol I and Pol III transcription
      supports its active role in promoting cell growth, proliferation, and the
      progression of liver carcinogenesis during HCV infection.

PMID- 14730213
TI  - Inhibition of tumor cell growth by Triton X-100 through specific effects on cell
      cycle-regulatory components.
AB  - A cross-linked form of the detergent Triton X-100, called Triton WR-1339, has
      been shown to reduce the spread of tumor cells in laboratory animals. However,
      some of these effects were controversial, probably due to the use of different
      tumor cell lines and varying sites of injection. In order to better understand
      these processes, we have used Triton X-100 and performed a molecular analysis of
      its growth-inhibitory function. Using the T24 bladder carcinoma cell line, we
      have shown that treatment of cells with this detergent caused a potent
      antiproliferative effect resulting from the downregulation of the key cell cycle
      regulators, the cyclin-dependent kinases (CDKs). CDK activity was lost due to a
      twofold effect, the increased expression of the CDK inhibitors p21(Cip1) and
      p27(Kip1) in combination with the reduced expression of cyclin A, a regulatory
      CDK subunit that is essential for CDK function. Taken together, our results
      provide a molecular basis for the antiproliferative effects of the Triton
      detergent, namely its differential effects on various parts of the cell cycle
      machinery.

PMID- 14730214
TI  - Down-regulation of human NDR gene in megakaryocytic differentiation of
      erythroleukemia K562 cells.
AB  - To study the control of hematopoietic cell differentiation, a human negative
      differentiation regulator (NDR) gene was identified by the comparative analysis
      of differentially expressed genes in hemato-lymphoid tissues. NDR is expressed
      preferentially in the adult bone marrow, fetal liver and testis.
      Immunocytochemistry with anti-NDR antiserum showed the presence of NDR in human
      erythroleukemia K562 cell line and CD34+ cells sorted from the umbilical cord
      blood. When fused to the green fluorescent protein (GFP), NDR was directed to the
      nucleus of mouse 3T3 and K562 cells. Fusion protein with a deletion from residues
      7 to 87 was detected in the cytoplasm. NDR appeared not to affect the
      proliferation of K562 cells when overly expressed. However, its expression was
      down-regulated during megakaryocytic differentiation of K562 cells induced by 12
      O-tetradecanoylphorbol-13-acetate (TPA). Down-regulation of NDR correlated well
      with up-regulation of megakaryocytic markers, CD41 and CD61. Overexpression of
      the nuclear NDR-GFP in K562 cells inhibited the expression of CD41 and CD61 in
      megakaryocytic differentiation. Treatment of K562 cells with GF-109203X (GFX), an
      antagonist of the protein kinase C (PKC), blocked NDR down-regulation, up
      regulated expression of CD41/CD61 and TPA-induced megakaryocytic differentiation.
      These results suggest a novel function of nuclear NDR protein in regulating
      hematopoietic cell development.

PMID- 14730215
TI  - Early detection of antibodies against various structural proteins of the SARS
      associated coronavirus in SARS patients.
AB  - Severe acute respiratory syndrome (SARS), a new disease with symptoms similar to
      those of atypical pneumonia, raised a global alert in March 2003. Because of its
      relatively high transmissibility and mortality upon infection, probable SARS
      patients were quarantined and treated with special and intensive care. Therefore,
      instant and accurate laboratory confirmation of SARS-associated coronavirus (SARS
      CoV) infection has become a worldwide interest. For this need, we purified
      recombinant proteins including the nucleocapsid (N), envelope (E), membrane (M),
      and truncated forms of the spike protein (S1-S7) of SARS-CoV in Escherichia coli.
      The six proteins N, E, M, S2, S5, and S6 were used for Western blotting (WB) to
      detect various immunoglobulin classes in 90 serum samples from 54 probable SARS
      patients. The results indicated that N was recognized in most of the sera. In
      some cases, S6 could be recognized as early as 2 or 3 days after illness onset,
      while S5 was recognized at a later stage. Furthermore, the result of recombinant
      protein-based WB showed a 90% agreement with that of the whole-virus-based
      immunofluorescence assay. Combining WB with existing RT-PCR, the laboratory
      confirmation for SARS-CoV infection was greatly enhanced by 24.1%, from 48.1% (RT
      PCR alone) to 72.2%. Finally, our results show that IgA antibodies against SARS
      CoV can be detected within 1 week after illness onset in a few SARS patients.

PMID- 14730216
TI  - Lung retrieval from non-heart-beating donors: first experience with an innovative
      preservation strategy in a pig lung transplantation model.
AB  - OBJECTIVE: Lung transplantation is limited by the scarcity of donor organs. Lung
      retrieval from non-heart-beating donors (NHBD) might extend the donor pool and
      has been reported recently. However, no studies in NHBD exist using the novel
      approach of retrograde preservation with Perfadex solution. METHODS: Heparinized
      asystolic pigs (n = 5, 30-35 kg) were ventilated for 90 min. The lungs were
      retrogradely preserved with Perfadex solution and stored inflated at 4 degrees C
      for 3 h. Left lung transplantation in the recipient was followed by exclusion of
      the right lung. Results were compared to sham-operated animals. Oxygenation,
      hemodynamics and dynamic compliance were monitored for 4 h. Infiltration of
      polymorphonuclear cells (PMNs) and stereological quantification of alveolar edema
      was performed. Statistical analysis comprised Kruskal-Wallis and Mann-Whitney
      tests and ANOVA analysis with repeated measures. RESULTS: No mortality was
      observed. During preservation, continuous elimination of blood clots via the
      pulmonary artery venting site was observed. Oxygenation and compliance were
      similar between groups, but sham controls showed significantly lower pulmonary
      vascular resistance. Stereological quantification revealed higher volume
      fractions of intra-alveolar edema in NHBD grafts, while PMN infiltration was
      comparable to sham controls. CONCLUSIONS: Use of NHBD lungs results in excellent
      outcome after 90 min of warm ischemia followed by retrograde preservation with
      Perfadex solution. This novel approach can optimize lung preservation by
      eliminating clots from the pulmonary circulation and might clinically be
      considered in brain-dead organ donors who become hemodynamically unstable prior
      to organ harvest. Further trials with longer warm and cold ischemic periods are
      necessary to further elucidate this promising approach to donor pool expansion.

PMID- 14730217
TI  - Total hepatectomy model in pigs: revised method for vascular reconstruction using
      a rigid vascular prosthesis.
AB  - Total hepatectomy in animals provides an irreversible model of acute liver
      failure. Vascular reconstruction in this model of acute liver failure was
      modified and characterized for the use of assessment of liver support systems.
      Pigs underwent total hepatectomy and a rigid three-way transparent polyethylene
      vascular conduit was used to replace the retrohepatic caval vein and to shunt the
      portal venous blood to the caval vein. Placement of the vascular conduit in
      conjunction with excision of the liver was completed in 10-22 min without the
      need of a temporary veno-venous bypass. A survival study conducted in 5 animals
      showed a mean survival time of 46 +/- 6 h. Baseline and 4 h postoperative
      hemoglobin levels were not different, and plasma ammonia levels rose to more than
      30-fold of baseline values. All animals died of cardiac arrhythmias and
      irreversible shock. Total hepatectomy in the pig using a three-way portal-venous
      conduit is a reliable and well-reproducible animal model of acute liver failure
      for evaluation of liver assist devices.

PMID- 14730218
TI  - Suppression of postoperative systemic inflammatory response syndrome with
      clarithromycin following lung cancer surgery.
AB  - We examined whether clarithromycin (CAM), a 14-membered macrolide, can control
      the postoperative systemic inflammatory response syndrome that occurs following
      lung cancer surgery. In the control group (n = 16), prophylactic antibiotics
      (flomoxef) were administered for 4-7 days following surgery. In the CAM group (n
      = 10), 400 mg/day of CAM were administered orally for 14 days prior to surgery
      and for 7 days following surgery, in addition to the postoperative administration
      of flomoxef. The incidence and duration of the systemic inflammatory response
      syndrome in the CAM group (30%, 0.3 days) were significantly lower than those in
      the control group (81%, 1.6 days). There were no significant differences between
      the control and CAM groups in both the amount and frequency of nonsteroidal anti
      inflammatory drugs following surgery. In conclusion, our study suggests that CAM
      may suppress the postoperative systemic inflammatory response syndrome in lung
      cancer patients.

PMID- 14730219
TI  - Effect of Mg2SO4 usage on spinal cord ischemia-reperfusion injury: electron
      microscopic and functional evaluation.
AB  - OBJECTIVES: To evaluate the effects of intravenous magnesium sulfate (Mg(2)SO(4))
      administration on ischemia-reperfusion injury of the spinal cord. MATERIAL AND
      METHODS: Sixteen rabbits were randomly assigned to the control (group I, 8
      rabbits) and the study group (group II, 8 rabbits). The abdominal aorta was
      clamped for a period of 30 min followed by a reperfusion period of 60 min. The
      animals in group II received 0.25 ml/kg/h Mg(2)SO(4) intravenous infusion (15%
      Mg(2)SO(4)) throughout this procedure. The animals were then observed for 24 h
      after which their neurological states were evaluated and tissue samples obtained
      from the spinal cord were examined with electron microscopy. RESULTS: Aortic
      pressure distal to the cross-clamp during the occlusion period was 9 +/- 3 mm Hg
      in group I and 19 +/- 6 mm Hg in group II. All animals in group I were paraplegic
      at the end of the study. In group II the neurological outcome of 1 animal was
      poor while the other 7 animals were neurologically in a good condition. Electron
      microscopic examinations of the spinal cord tissues of group I revealed severe
      injury but the ultrastructure was well preserved in group II. CONCLUSIONS:
      Intravenous Mg(2)SO(4) administration may have protective effects on the ischemia
      reperfusion injury of the spinal cord. We propose that Mg(2)SO(4) may be an
      additional protective pharmacological agent in thoracal and thoracoabdominal
      aortic surgery.

PMID- 14730220
TI  - Value of energy substrates in HTK and UW to protect human liver endothelial cells
      against ischemia and reperfusion injury.
AB  - Adenosine 5'-triphosphate (ATP) depletion is a major cause of cellular injury
      during ischemia and reperfusion in organ transplantation. Therefore, histidine
      tryptophan-ketoglutarate solution (HTK; alpha-ketoglutarate) and University of
      Wisconsin solution (UW; adenosine) were supplied with energy substrates to
      achieve graft viability. Nevertheless, their efficacy for maintaining the ATP
      level, particularly in human liver endothelial cells, was uncertain. Furthermore,
      it is of interest whether a high ATP level is beneficial in human liver
      endothelial cell viability. We used human liver endothelial cells between the 3rd
      and 6th passages in a cell culture model. Human liver endothelial cells were
      exposed to hypothermic preservation (4 degrees C) in HTK and UW for 2, 6, 12, 24
      and 48 h with subsequent reperfusion of 6 h. ATP and lactate dehydrogenase (LDH)
      were measured after each interval. In comparison to HTK, UW demonstrates a
      statistically significantly higher level of ATP after each interval of ischemia
      (p < 0.001) and reperfusion (p < 0.002). Additionally, UW-preserved human liver
      endothelial cells exceed the ATP level of the warm control during all intervals
      of ischemia. The loss of cell viability (LDH) was statistically significantly
      higher after ischemia (p < 0.01) and reperfusion (p < 0.01) in HTK than in UW
      except after the interval of 48 h. In conclusion, adenosine was more effective
      than alpha-ketoglutarate in maintaining a high ATP level in human liver
      endothelial cells after ischemia and reperfusion. Different pathways of energy
      substrate utilization were a contributing factor. The beneficial effect of the
      higher ATP level caused by adenosine to human liver endothelial cell viability
      was limited to 24 h of ischemia. Beyond this ischemia time we could not prove a
      favorable impact of adenosine on human liver endothelial cells.

PMID- 14730221
TI  - Effects of combined nutritional therapy on acute necrotizing pancreatitis in rats
      in the early phase of the disease.
AB  - The aim of this study was to investigate the influence of a small amount of
      enteral nutrition along with parenteral nutrition on acute necrotizing
      pancreatitis (ANP) induced by glycodeoxycholic acid in rats in the early phase of
      disease. The induction of ANP resulted in a significant increase in mortality
      rate, intestinal permeability, bacterial infection in the pancreas and
      extrapancreatic organs, pancreatic necrosis and serum activity of urea and
      amylase, and a significant decrease in concentrations of calcium, protein and
      albumin. But no difference was observed between the pancreatitis groups.
      Significant hyperglycemia and increased liver transaminase activity were observed
      in rats treated with combined nutritional therapy (CNT). CNT did not improve the
      course of acute pancreatitis, intestinal permeability, bacterial translocation,
      or reduce the extent of acinar cell injury in ANP and is therefore unlikely to be
      of benefit in patients with pancreatitis in the early period.

PMID- 14730222
TI  - Interleukin-10 suppresses proliferation and remodeling of extracellular matrix of
      cultured human skin fibroblasts.
AB  - When we previously examined the participation of local expression of interleukin
      10 (IL-10) and tumor necrosis factor-alpha (TNFalpha) in wound healing of an
      intestinal anastomosis under septic conditions in mice, we found that IL-10 and
      TNFalpha expressions were markedly enhanced around the anastomosis and that wound
      healing was impaired in this animal model. The purpose of the present study was
      to investigate the combined effect of IL-10 on proliferation and remodeling of
      the extracellular matrix (ECM) of cultured human skin fibroblasts. Human skin
      fibroblasts were cultured for 48 h with IL-10 and/or TNFalpha at various
      concentrations, then the proliferation rates were determined using the MTT [3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The
      concentration of transforming growth factor-beta1 (TGFbeta1) in cell culture
      supernatants was measured by enzyme-linked immunosorbent assay, and type I
      collagen protein and matrix metalloproteinase-I (MMP-I) were detected by indirect
      immunofluorescence in cultured cells incubated for 48 h with 10 ng/ml of IL-10
      and/or 10 ng/ml of TNFalpha. IL-10 itself had no effect on fibroblast
      proliferation, but reduced TNFalpha-induced fibroblast proliferation. The
      concentration of TGFbeta1 in cell culture supernatants was significantly lower in
      the presence of TNFalpha and IL-10 than in the presence of TNFalpha alone.
      Immunolabeling of fibroblasts for type I collagen protein was decreased in cells
      incubated with IL-10 and/or TNFalpha compared to controls. MMP-I immunolabeling
      was increased in cells incubated with IL-10, IL-10 and TNFalpha compared to
      control and cells incubated with TNFalpha. It is suggested that IL-10 is an
      inhibitory factor for the remodeling of the ECM during wound healing.

PMID- 14730223
TI  - Effect of different enteral nutrients on bacterial translocation in experimental
      obstructive jaundice.
AB  - Obstructive jaundice leads to bacterial translocation (BT) by disruption of the
      gut barrier, intestinal microecology, and impaired host immune defence. The
      objective of the present study is to investigate the effects of different enteral
      nutrients on BT that is induced by obstructive jaundice in rats. Eighty male
      Wistar-Albino rats were randomly assigned into 4 groups. Group 1: 20 rats
      underwent laparotomy, common bile duct (CBD) was not actually ligated and
      transected, but sham ligation of CBD was performed. Groups 2-4: 60 rats underwent
      laparotomy, CBD ligation and transection. Group 1 and 2 rats were given rat chow,
      group 3 rats were fed a glutamine and arginine supplemented enteral diet, and
      group 4 rats were fed an arginine, m-RNA and omega-3 supplemented enteral diet,
      an immunonutrient. Rats in groups 3 and 4 had significantly less BT to mesenteric
      lymph nodes compared to rats in group 2 (p = 0.001). These findings suggest that
      oral administration of an arginine and glutamine supplemented diet and
      immunonutrition reduce BT in rats with obstructive jaundice.

PMID- 14730224
TI  - Effectiveness of coagulation factor XIII concentrate for reversing loss of
      tensile strength of rat intestinal anastomoses.
AB  - BACKGROUND: Blood coagulation factor XIII (F-XIII) promotes cross-linking of
      fibrin during blood coagulation. Impaired clot stabilization in patients with
      genetic deficiencies of F-XIII is associated with marked pathologies of wound
      healing. METHODS: 60 rats given carbon tetrachloride underwent ileal anastomosis
      after which they received albumin (Alb animals) or F-XIII concentrate (F-XIII
      animals) immediately after surgery and daily thereafter until day 2 or 4 and were
      euthanized on day 3 or 5, respectively, or until day 5 and were euthanized on day
      7, 10, or 21. We measured the plasma F-XIII activity and anastomotic tensile
      strength, followed by immunohistochemical localization of F-XIII subunit A within
      anastomoses. RESULTS: On day 3, there were no significant differences between Alb
      and F-XIII animals for plasma F-XIII activity and tensile strength, and both
      groups of animals showed little immunostaining for F-XIII on anastomoses. Plasma
      F-XIII activities did not differ between Alb and F-XIII animals on day 5 (115.8
      +/- 16.8 vs. 137.3 +/- 14.9%). Although the tensile strength in both groups was
      increased compared with that of day 3, that in F-XIII animals (129.8 +/- 3.3 gf)
      was significantly higher than that in Alb animals (100.8 +/- 5.3 gf, p = 0.014).
      F-XIII animals showed de novo collagen fibers and intense immunoreactivity of F
      XIII in the extracellular matrix around the anastomoses. Similar differences
      occurred on day 7 but not days 10 and 21. CONCLUSIONS: F-XIII concentrate may
      accelerate the early healing process of intestinal anastomosis because of the
      protein's accumulation in situ.

PMID- 14730225
TI  - Effects of locally applied recombinant human granulocyte-macrophage colony
      stimulating factor on ischemic bowel anastomoses in rat.
AB  - BACKGROUND: Ischemia is one of the most common causes of anastomosis disruption.
      In the present study we investigated the effect of locally injected recombinant
      human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on ischemic
      bowel anastomosis in rats. METHODS: 144 male Sprague-Dawley rats were randomized
      into four groups: in group 1, colon anastomoses were performed; in group 2,
      anastomoses were performed then 50 microg rhGM-CSF was injected subserosally into
      the perianastomotic area; in group 3, anastomoses were performed on ischemic
      colon segments, and in group 4, colon anastomoses were performed on ischemic
      segments and then 50 microg rhGM-CSF was injected subserosally into the
      perianastomotic area. On the 3rd and 7th post-operative days, the rats were
      sacrificed and anastomotic bursting pressures were measured. Hydroxyproline
      contents were studied on the tissues from the anastomotic line. Three anastomotic
      segments were saved from each group for histopathological studies before bursting
      pressure measurement. RESULTS: The bursting pressure in group 3 was significantly
      weaker than in the other groups. There were no significant differences between
      the bursting pressures in groups 1 and 4. The levels of hydroxyproline content in
      group 4 were significantly greater than in group 3. CONCLUSIONS: These data
      suggest that the local injection of rhGM-CSF improves the healing of ischemic and
      even normal colon anastomoses.

PMID- 14730226
TI  - Experimental heterotopic heart transplantation: an easier technique.
AB  - AIM: The use of heterotopic heart transplantation (HHT) in experimental surgery
      is an extended method to evaluate cardiac graft viability. To study endothelial
      injury after ischemia-reperfusion, the technique described by Matsui et al. in
      1988 for HHT was chosen. A modification, which consists of replacing the atrium
      to-atrium anastomosis for the tip of a 30-Fr venous cannula, was developed with
      the purpose of using this technique in small pigs. Both techniques were compared.
      METHODS: Twenty-seven consecutive HHTs in 17- to 20-kg pigs using Matsui's
      original technique and the modified technique were performed. Ischemia time,
      bleeding volume, mean gradient and anastomosis complications were measured to
      compare both techniques. RESULTS: Statistically significant decreases in ischemia
      time, bleeding volume and mean gradient with the modified technique were found.
      Furthermore, there were two cases of suture dehiscence with the original
      technique. CONCLUSIONS: The replacement of the atrium-to-atrium anastomosis for
      the venous cannula is a modification that statistically decreases the ischemia
      time, blood loss and avoids suture complications. This modification makes
      Matsui's technique easier, faster and safer in small pigs and it may be used in
      bigger animals and in any kind of non-permanent anastomosis.

PMID- 14730227
TI  - Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus
      arteriosus and pupillary dysfunction: a new genetic syndrome?
AB  - We report on 2 children with moyamoya angiopathy and bilateral dolichoectatic
      internal carotid arteries in combination with iris hypoplasia with bilateral
      fixed dilated pupils and a history of patent ductus arteriosus. Both were
      symptomatic with moyamoya angiopathy and underwent bilateral extracranial
      intracranial (EC-IC) bypass operations for cerebral revascularization. This is
      the first report on moyamoya angiopathy and bilateral dolichoectatic internal
      carotid arteries with simultaneous occurrence of ocular and cardiovascular
      malformations. There have been descriptions of cerebral vascular abnormalities in
      combination with either congenital heart disease or ocular abnormalities but not
      with both presenting together. The combination of these separate congenital
      developmental defects may not be purely coincidental: we propose that the 2
      probands are affected with a not yet recognized clinical syndrome of probably
      genetic etiology.

PMID- 14730228
TI  - The International League of Dermatological Societies: from the World Congress of
      Dermatology to the international foundation for dermatology and beyond.

PMID- 14730229
TI  - Group a beta-haemolytic streptococcal necrotising fasciitis: early diagnosis and
      clinical features.
AB  - Necrotising fasciitis (NF) due to group A beta-haemolytic streptococci (GAS) is a
      rare but still life-threatening soft-tissue infection characterised by rapidly
      spreading inflammation and subsequent necrosis of the muscle fascia and of the
      surrounding tissues. Previous studies have emphasised that the outcome of
      patients with NF depends essentially on early diagnosis and treatment, consisting
      of extensive surgical debridement, along with appropriate antibiotic therapy.
      However, one of the striking features of the published series of GAS NF is that
      there was a delay in diagnosis in several cases, which underscores the difficulty
      of the early diagnosis of the condition. The goal of this article was to review
      the clinical features and diagnostic tools that could facilitate the early
      recognition of GAS NF.

PMID- 14730230
TI  - Takayasu's disease with cutaneous involvement.
AB  - Takayasu's arteritis (TA) is a chronic inflammatory and fibrosing arteriopathy
      that can also involve cutaneous vessels. The disease typically presents with a
      prepulseless phase that overlaps or is followed by the characteristic pulseless
      stage. In both phases of TA, cutaneous manifestations may be present. Lesions
      considered to be 'specifically' associated with TA have been described most
      frequently simulating erythema nodosum, erythema induratum and pyoderma
      gangrenosum. We report 2 Caucasian patients with TA and nodular cutaneous
      lesions. Nine skin biopsies from these patients were studied. A necrotizing
      vasculitis was present in 5 biopsies. We review those patients with TA and well
      documented cutaneous manifestations in the English literature, with special
      interest in nodular lesions, the most frequent cutaneous manifestation of TA in
      Caucasian patients. Biopsies from lesions with similar morphology frequently show
      different histological findings.

PMID- 14730231
TI  - Clinical criteria for the diagnosis of bullous pemphigoid: a reevaluation
      according to immunoblot analysis of patient sera.
AB  - BACKGROUND: We previously proposed a set of 4 clinical criteria for the diagnosis
      of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence
      of atrophic scars, absence of mucosal involvement and absence of predominant
      bullous lesions on the neck and head. These results have been challenged because
      direct immunoelectron microscopy (IEM), which was used as the standard diagnostic
      criterion in our initial study, does not identify the different antigens of the
      basement membrane zone. OBJECTIVE: To reassess the validity of these clinical
      criteria for the diagnosis of BP using immunoblot analysis of patient sera as the
      main diagnostic criterion, in order to precisely identify the antigens recognized
      by patient sera. METHODS: One hundred and eighty-nine sera from patients with
      various subepidermal autoimmune blistering diseases (AIBDs) were tested by
      immunoblotting using dermal and epidermal extracts. IEM was used as a
      complementary diagnostic procedure in a few patients whose serum recognized BPAG2
      exclusively or was negative in immunoblotting. RESULTS: 142 patients (75%) had at
      least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the
      set of BP clinical criteria were more frequently immunoblot negative (34%) than
      sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more
      frequently recognized by sera from patients with the set of BP clinical criteria
      (78%) than by sera from patients without the criteria (45%; p = 5.10(-4)). In
      contrast, BPAG2 was recognized by a great number of sera from patients who lacked
      the criteria of BP (71%), which was in accordance with the presence of numerous
      patients with cicatricial pemphigoid in this group. Among patients with various
      subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%,
      a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of
      these clinical criteria were present. CONCLUSION: These results confirm the
      interest of this set of clinical criteria for the rapid diagnosis of BP.

PMID- 14730232
TI  - Automated extraction and description of dark areas in surface microscopy
      melanocytic lesion images.
AB  - BACKGROUND: Identification of dark areas inside a melanocytic lesion (ML) is of
      great importance for melanoma diagnosis, both during clinical examination and
      employing programs for automated image analysis. OBJECTIVE: The aim of our study
      was to compare two different methods for the automated identification and
      description of dark areas in epiluminescence microscopy images of MLs and to
      evaluate their diagnostic capability. METHODS: Two methods for the automated
      extraction of 'absolute' (ADAs) and 'relative' dark areas (RDAs) and a set of
      parameters for their description were developed and tested on 339 images of MLs
      acquired by means of a polarized-light videomicroscope. RESULTS: Significant
      differences in dark area distribution between melanomas and nevi were observed
      employing both methods, permitting a good discrimination of MLs (diagnostic
      accuracy = 74.6 and 71.2% for ADAs and RDAs, respectively). CONCLUSIONS: Both
      methods for the automated identification of dark areas are useful for melanoma
      diagnosis and can be implemented in programs for image analysis.

PMID- 14730233
TI  - Three-point checklist of dermoscopy. A new screening method for early detection
      of melanoma.
AB  - BACKGROUND: Dermoscopy used by experts has been demonstrated to improve the
      diagnostic accuracy for melanoma. However, little is known about the diagnostic
      validity of dermoscopy when used by nonexperts. OBJECTIVE: To evaluate the
      diagnostic performance of nonexperts using a new 3-point checklist based on a
      simplified dermoscopic pattern analysis. METHODS: Clinical and dermoscopic images
      of 231 clinically equivocal and histopathologically proven pigmented skin lesions
      were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the
      nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue
      white structures) constituting the 3-point method. In addition, all examiners
      made an overall diagnosis by using standard pattern analysis of dermoscopy.
      RESULTS: Asymmetry, atypical network and blue-white structures were shown to be
      reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55.
      When making the overall diagnosis, the expert had 89.6% sensitivity for malignant
      lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared
      to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of
      the nonexperts using the 3-point checklist reached 96.3%. The specificity of the
      expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by
      the nonexperts using overall diagnosis and 3-point checklist, respectively.
      CONCLUSION: The 3-point checklist is a valid and reproducible dermoscopic
      algorithm with high sensitivity for the diagnosis of melanoma in the hands of non
      experts. Thus it may be applied as a screening procedure for the early detection
      of melanoma.

PMID- 14730234
TI  - Teaching effects of dermatological consultations on nondermatologists in the
      field of internal medicine. A study of 1290 inpatients.
AB  - BACKGROUND: Scarce data exist concerning dermatological consultations within
      departments of internal medicine. To date, no survey has been carried out in
      Switzerland to elucidate this issue. The aim of this study was to analyze the
      spectrum of skin diseases internists are confronted with and to study their
      diagnostic accuracy in cutaneous diseases. In addition, we wanted to evaluate the
      motivation for dermatologists to cooperate closely with internists. PATIENTS AND
      METHODS: The study included patients with dermatological problems treated at the
      Department of Internal Medicine at the Kantonsspital Aarau, Switzerland. All
      patients had been referred to the Department of Dermatology for examination
      between 1999 and 2001. Patient data were analyzed demographically, by referral
      modus, diagnoses and therapy. To evaluate the knowledge of internists and
      dermatologists in cutaneous medicine, 15 clinical slides of common dermatoses
      with a patient history were shown and asked for diagnostic suggestions to 32
      internists of the Kantonsspital Aarau and to 13 dermatologists of the University
      Hospital Basel, Switzerland. RESULTS: 1290 patients were referred to the
      Department of Dermatology. 1737 dermatological diagnoses were made including 348
      different dermatoses. Eczema was the single most common diagnosis (12.6%),
      followed by actinic and bowenoid precancerosis (6.2%), drug eruption (4.2%),
      verrucae (4%) and mycosis (3.8%). The top ten diagnoses accounted for 41.7% of
      all skin-related diagnoses. Infection-related dermatoses were most common (20.5%)
      followed by different types of eczema (12.6%), malignant cutaneous tumors and
      malignant visceral conditions (11.2%). Local therapy was prescribed in 64.2% and
      systemic therapy in 22.6% of the patients. 15.9% did not receive specific therapy
      because the consultation request was only a diagnostic one. 146 skin biopsies
      were performed (11.3%). Systemic diseases with cutaneous manifestations accounted
      for 15.7%. In general, these conditions were not commonly seen by dermatologists
      in daily practice. The internists recognized 51.1% of the cutaneous
      manifestations during examination and 49% when presented with slides.
      CONCLUSIONS: Internists are confronted with a different spectrum of cutaneous
      diseases compared with dermatologists. Due to the broad spectrum of skin
      diseases, it is a challenging task for internists to recognize dermatoses. Our
      study elucidates that patients, internists and dermatologists may profit from a
      close cooperation.

PMID- 14730235
TI  - Study design and preliminary results from the pilot phase of the PraKtis study:
      self-reported diagnoses of selected skin diseases in a representative sample of
      the Italian population.
AB  - BACKGROUND: Few data are available on the prevalence of common skin disorders
      like actinic keratoses in the general population. Such data are mostly needed to
      better define health needs and to organize medical services. The Prevalence of
      Actinic Keratoses in the Italian Population Study (PraKtis) was designed to
      estimate the point prevalence of actinic keratoses and related disorders, e.g.
      photoaging, in a representative sample of the Italian population. Within the
      study, information on the history of relevant dermatological diagnoses was also
      collected. METHODS: The study was conducted in collaboration with DOXA, the
      Italian branch of the Gallup International Association. A representative sample
      of people aged 45 years or older was selected by picking them from the electoral
      rolls according to a stratified random sampling design involving a replacement
      procedure. A total of 180 interviewers specifically trained to collect data on
      skin diseases and to take photographs of representative lesions on the face and
      upper limbs, contacted and interviewed the sampled subjects and performed a face
      to-face computer-assisted interview. A final sample of about 12000 subjects was
      foreseen. RESULTS: The pilot phase of the study was conducted between January 1
      and June 30, 2003. A total of 3660 subjects were recruited and interviewed.
      Overall, an estimated 37% of Italian people reported having ever undergone a
      dermatological consultation in the past. An estimated 29% reported having ever
      received a specific dermatological diagnosis by a physician. The frequency of
      specifically enquired diagnoses, weighted according to the distribution of the
      Italian population, was as follows: atopic dermatitis 4.7%, other eczematous
      dermatitides 4.3%, urticaria 4.3%, psoriasis 3.1%, skin tumors 1.6%, vitiligo
      0.7% and actinic keratoses 0.3%. CONCLUSION: Skin diseases are frequently
      reported. The prevalence of actinic keratoses according to self-reported
      diagnoses was lower than expected based on prevalence data obtained by directly
      examining people. These discrepancies may be due to underreporting and/or
      unawareness of lesions by affected people. More precise estimates will be
      obtained by direct examination of sampled people.

PMID- 14730236
TI  - Interferon alpha as adjuvant postsurgical treatment of melanoma: a meta-analysis.
AB  - BACKGROUND: The literature on the benefit of alpha-interferon (IFN-alpha) as
      adjuvant postsurgical treatment of melanoma reports discordant results.
      OBJECTIVE: With the published data so far, we performed a meta-analysis in order
      to evaluate the effect of IFN-alpha on the relapse rate (RR) and the overall
      survival (OS). METHODS: Published randomised trials were identified by Medline
      search. Stage IV melanoma was not considered. RESULTS: Nine published studies
      were included, with a total of 2,880 patients. Both the per protocol and the
      intention-to-treat analysis show that IFN-alpha significantly decreased the RR
      (OR = 0.74; 95% CI = 0.64-0.86). Subgroup analyses show that, for all stages,
      high and low doses decreased the RR (OR = 0.71, 95% CI = 0.54-0.92, and OR =
      0.76, 95% CI = 0.63-0.91, respectively). No difference has been evidenced on OS.
      CONCLUSIONS: High and low doses of IFN-alpha significantly decrease the RR, but
      the OS does not seem to be improved.

PMID- 14730237
TI  - A prospective study of cutaneous adverse events induced by low-dose alpha
      interferon treatment for malignant melanoma.
AB  - INTRODUCTION: alpha-Interferon is associated with numerous cutaneous side
      effects, but the accurate incidence of these complications is not clearly known.
      OBJECTIVES: A prospective study was designed to evaluate the incidence and
      clinical pattern of cutaneous side effects in a cohort of patients receiving
      adjuvant therapy with low-dose interferon for malignant melanoma. MATERIAL AND
      METHODS: A cohort of 33 patients with stage IIA and IIB melanoma treated with low
      dose alpha-interferon (3 MIU 3 times a week for 18 months) were prospectively
      enrolled in a single-center study. The patients responded to a questionnaire on
      their medical history and were systematically examined for any cutaneous lesions
      before treatment and every 3 months afterwards. RESULTS: 29/33 patients (87%)
      experienced 1 or more cutaneous side effects. The most frequent was hair loss and
      occurred in 16 cases (48.4%). Hair discoloration was noted in 6 cases (18%).
      Eczematous reactions at injection sites or at remote sites were observed in 13
      patients (39%). Pruritus occurred in 10 cases (30%). Xerostomia, Raynaud's
      phenomenon or livedo reticularis were observed in 10 patients, associated with an
      increase in circulating autoantibody titer in 2 cases. Some rare side effects
      were observed: urticaria (1 case) or angioedema (1 case), worsening of
      preexisting seborrheic dermatitis (3 cases), herpetic recurrence (2 cases),
      pityriasis versicolor (1 case), worsening of recurrent buccal aphthous ulcer (1
      case) and vitiligo (1 case). CONCLUSION: Cutaneous adverse events during adjuvant
      immunotherapy of melanoma with low-dose alpha-interferon seem to be frequent but
      do not result in treatment discontinuation. A good awareness of these side
      effects may be useful for a more accurate survey and clinical management of
      patients receiving this treatment.

PMID- 14730238
TI  - Single-dose fluconazole versus itraconazole in pityriasis versicolor.
AB  - BACKGROUND: The new antifungal triazoles itraconazole and fluconazole have
      revolutionized the treatment of pityriasis versicolor. Both drugs have shown
      promising results in different dose schedules. OBJECTIVE: To compare the efficacy
      and safety of single oral dose treatment with fluconazole versus itraconazole in
      patients with pityriasis versicolor. METHODS: A total of 40 patients with
      pityriasis versicolor were allocated randomly to group A and group B. A single
      dose of fluconazole (400 mg) or itraconazole (400 mg) was given orally to group A
      or group B patients, respectively. Patients were assessed mycologically by KOH
      and culture. Culture was done from lesional and perilesional skin to quantify
      growth and to observe the effect of these drugs and the persistence/reappearance
      of the fungus in relation to relapse at 2 and 8 weeks. Relapse was defined as
      reappearance or worsening of clinical signs and symptoms or positive KOH/culture
      after initial improvement. RESULTS: Thirteen (65%) patients in the fluconazole
      group and 4 (20%) patients in the itraconazole group became culture negative at
      the end of 8 weeks. Relapse was found to be higher in the itraconazole group
      compared to the fluconazole group (60 vs. 35%). A direct correlation was found
      between the relapse rate and positivity of perilesional skin for Malassezia
      furfur. CONCLUSION: In the same dosing, fluconazole was found to be more
      effective than itraconazole; however, both drugs were found to be safe.

PMID- 14730239
TI  - Possibility of treating basal cell carcinomas of nevoid basal cell carcinoma
      syndrome with superficial x-ray therapy.
AB  - BACKGROUND: The nevoid basal cell carcinoma syndrome (NBCCS), also known as
      Gorlin-Goltz syndrome, is a rare dermatological disease inherited according to an
      autosomal dominant pattern. From the dermatological point of view, the most
      evident characteristic of the syndrome is the early onset of multiple basal cell
      carcinomas (BCCs). An ideal treatment of BCCs of the NBCCS does not exist.
      OBJECTIVE: To evaluate if in particular cases (e.g. poor general health
      conditions, previous multiple surgical excisions) radiotherapy may be useful,
      under the condition that it does not promote the onset of new BCCs and that the
      healing of irradiated lesions is normal. METHODS: A study on 3 patients with 17
      BCCs treated with superficial radiotherapy is here reported. RESULTS: Complete
      remission without carcinogenic effects was reached in all treated lesions, with a
      mean follow-up of 30.35 months. CONCLUSION: In our opinion, such results suggest
      the possibility of a cautious application of superficial radiotherapy in selected
      cases of NBCCS.

PMID- 14730241
TI  - Eruptive vellus hair cyst in patients with chronic renal failure.
AB  - Two cases of eruptive vellus hair cysts associated with chronic renal failure are
      reported. Histologically the lesions of both cases showed cystic structures in
      the dermis lined by squamous epithelium which contained varying amounts of vellus
      hair shafts. Immunohistochemical studies using monoclonal anti-AGE (advanced
      glycation end product) antibody demonstrated that keratinous materials within the
      cystic structures were immunoreactive to the antibody, whereas those of cystic
      lesions (epidermal cyst, eruptive vellus hair cyst, steatocystoma multiplex,
      trichofolliculoma and trichilemmal cyst) seen in otherwise healthy individuals
      were negative. Because it has been reported that plasma and skin levels of AGE
      are elevated in renal failure patients, AGE-modified keratinous materials may be
      associated with the formation of cystic structures by stimulating the occlusion
      of the epithelium.

PMID- 14730240
TI  - Coexistence of HLA-B*08 and HLA-B*18 in four siblings with Lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS), is characterized by localized patches of
      atrophy and whitening of the skin. The cause of LS remains unknown, but genetic,
      hormonal, immunologic factors and autoimmune mechanisms have been incriminated.
      There are conflicting data regarding the association between LS and human
      leukocyte antigens (HLA). METHODS: We have analyzed the HLA alleles of a family,
      in which 4 of 5 children have lichen sclerosus. RESULTS: HLA-B*08 and HLA-B*18
      alleles were detected in children with LS, but not in a healthy sister. None of
      the patients had autoimmune disease. CONCLUSION: In our opinion, coexistence of
      these two alleles may play a role in the development of LS.

PMID- 14730242
TI  - Caterpillar dermatitis in two siblings due to the larvae of Thaumetopoea
      processionea L, the oak processionary caterpillar.
AB  - Two siblings, 16 months and 5 years of age, came into contact with the urticating
      hairs (setae) of oak processionary caterpillars, the larvae of Thaumetopoea
      processionea L., when the family moved to a suburb of Vienna, where mass
      gradation of T. processionea had started the year before. The setae were being
      spread by the wind from an infested oak tree in the neighbourhood. Both children
      repeatedly suffered bouts of dermatitis during the 10 weeks of the larval
      development. Owing to the fact that T. processionea often infests oak trees,
      whether isolated or at the edges of forests, there is a high likelihood of people
      being affected. Children frequently explore their surroundings and are at an even
      greater risk of developing lepidopterism. Caterpillar dermatitis should therefore
      be taken into consideration in the differential diagnosis of a pruritic rash in
      infants from regions with caterpillar-infested trees, especially during the
      larval development of T. processionea .

PMID- 14730243
TI  - Myoepithelioma possibly originating from the accessory parotid gland.
AB  - Myoepithelioma originates almost exclusively from myoepithelial cells of the
      salivary, prostate and mammary glands. The skin is a very rare site where
      myoepithelioma occurs. We describe a patient with a myoepithelioma on the right
      cheek seen as a subcutaneous nodule that was separated from the parotid gland at
      surgical resection. Histopathological findings were consistent with those of a
      myoepithelioma that had originated from the parotid gland, suggesting that this
      tumor may have developed from the accessory parotid gland.

PMID- 14730244
TI  - Improvement of SLE skin rash with granulocyte and monocyte adsorption apheresis.

PMID- 14730245
TI  - Spontaneous tolerance to terbinafine-induced lichenoid drug eruption.

PMID- 14730246
TI  - Localized Darier's disease of the scalp: successful treatment with oral
      etretinate.

PMID- 14730247
TI  - Furunculosis and IgG subclass deficiency.

PMID- 14730248
TI  - Is acute idiopathic scrotal edema in children a special feature of neutrophilic
      eccrine hidradenitis?

PMID- 14730250
TI  - Gianotti-crosti syndrome in India is not associated with hepatitis B infection.

PMID- 14730251
TI  - Role of inflammation in stroke and atherothrombosis.
AB  - The onset of cerebral ischaemia triggers a cascade of proinflammatory molecular
      and cellular events. Clinical studies suggest that the strength of this acute
      response is important in early and late clinical outcomes, early clinical
      worsening, and extent of brain damage. Variables that are predictors of adverse
      stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive
      protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular
      adhesion molecule-1. Current data indicate that inflammation serves to fuel
      atherosclerosis and can act as the link between atherosclerosis and
      atherothrombosis. Growing evidence indicates that platelets act as prominent
      players in the inflammatory component of these disease processes. Thus, upon
      activation, platelets release a series of cytokines and growth factors and
      express CD40 ligand, which interacts with the CD40 receptor on other major cell
      types involved in atherosclerosis/atherothrombosis. In healthy volunteers, CD40L
      expression in platelets is not significantly inhibited by acetylsalicylic acid
      (ASA) alone, but is inhibited after treatment with the ADP-receptor antagonist
      clopidogrel or with clopidogrel plus ASA. Of a range of potential inflammatory
      biomarkers that have been reported in the literature, the best studied is CRP.
      Such biomarkers may have clinical utility for refined identification of patients
      at high risk for atherothrombosis in different arterial beds and for monitoring
      of therapeutic agents in clinical trials.

PMID- 14730252
TI  - Recent clinical trial results with antiplatelet therapy: implications in stroke
      prevention.
AB  - Dual antiplatelet therapy that inhibits more than one pathway of platelet
      activation is appealing and biologically rational. The CURE study evaluated the
      efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus
      standard therapy (including ASA) in over 12,000 patients with unstable angina or
      non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination
      with ASA reduced the relative risk of the combined atherothrombotic endpoint of
      cardiovascular death, MI or stroke by 20% (95% CI 0.72-0.90; p < 0.001) and the
      absolute risk of this composite endpoint by 2.1%. While the study was not powered
      or designed to demonstrate a reduction in stroke, there was a 14% reduction in
      stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an
      acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI
      CURE, a prespecified substudy of patients who underwent percutaneous coronary
      intervention (PCI) during CURE, confirmed the early and sustained benefits of
      clopidogrel therapy seen in the overall CURE study. CREDO was a randomized,
      double-blind, placebo-controlled trial in more than 2,100 patients that evaluated
      the continuation of clopidogrel on top of standard therapy including ASA for 12
      months after PCI, and the benefit of a preprocedural clopidogrel loading dose.
      The long-term results at 1 year showed that there was a 27% reduction in the risk
      of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a
      consistent benefit of extended clopidogrel therapy for each component of the
      composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In
      patients who received clopidogrel > or =6 h before PCI, there was a 39% reduction
      in the risk of death, MI or urgent target-vessel revascularization at 28 days (p
      = 0.051). These data suggest important implications in the future for the use of
      an early loading dose of clopidogrel in patients undergoing carotid stenting and,
      if proven in current or future trials, the use of a loading dose followed by long
      term continuation of clopidogrel in other high-risk atherothrombotic patients
      such as those with transient ischaemic attack or ischaemic stroke.

PMID- 14730253
TI  - Ongoing and planned trials of antiplatelet therapy in the acute and long-term
      management of patients with ischaemic brain syndromes: setting a new standard of
      care.
AB  - Among high vascular risk patients, acetylsalicylic acid (ASA) reduces the
      relative risk of serious vascular events by about one fifth. However, because ASA
      fails to prevent four fifths of serious vascular events, more effective, yet
      equally safe and affordable, antiplatelet regimens are desired. Compared with
      ASA, clopidogrel alone reduces the odds of serious vascular events by about 10%,
      and the combination of dipyridamole and ASA reduces the odds of serious vascular
      events by about 6%. Combining ASA with an orally administered platelet
      glycoprotein (GP) IIb/IIIa blocker is not effective, and indeed more hazardous
      than ASA alone. Among patients with non-ST-segment acute coronary syndromes
      (ACS), the addition of an intravenously administered GP IIb/IIIa receptor
      antagonist to ASA reduces the risk of vascular events by about 10% compared with
      ASA, and the addition of clopidogrel to ASA reduces the risk of vascular events
      by 20% compared with ASA alone. Among patients undergoing percutaneous coronary
      intervention (PCI), both the addition of an intravenously administered GP
      IIb/IIIa receptor antagonist to ASA, and the addition of clopidogrel to ASA
      reduce the risk of vascular events by 30% compared with ASA alone. The greater
      efficacy of the combinations of ASA with clopidogrel, and ASA with an
      intravenously administered GP IIb/IIIa receptor antagonist, in patients with ACS
      and those undergoing PCI has fostered several ongoing and planned trials of these
      regimens in the acute and long-term management of patients with ischaemic brain
      syndromes. The combination of ASA and clopidogrel is being compared with ASA
      alone within 12 h of onset of symptoms of TIA in two trials (FASTER, ATARI), and
      the use of an intravenously administered GP IIb/IIIa receptor antagonist is being
      compared with placebo within 6 h of onset of acute ischaemic stroke in two trials
      (AbESST, AbESST-2). Six trials are assessing the combination of clopidogrel and
      ASA in the long-term management of patients with ischaemic brain syndromes due to
      atherothrombosis (MATCH, CHARISMA, ARCH, CARESS, SPS3) or atrial fibrillation
      (ACTIVE). The MATCH trial of clopidogrel and ASA versus clopidogrel alone in
      patients with recent TIA or ischaemic stroke is the first which is likely to
      report its results - in mid 2004. The combination of dipyridamole and ASA is
      being compared with ASA in the ESPRIT trial and with the combination of
      clopidogrel and ASA in the planned PRoFESS trial. These ongoing and planned
      clinical trials of antiplatelet therapy promise to further define the role of
      combination antiplatelet therapy in the acute and long-term management of
      patients with ischaemic brain syndromes.

PMID- 14730254
TI  - The unstable plaque.
AB  - Ischaemic strokes and transient ischaemic attacks are commonly caused by cerebral
      embolism originating from formation of a platelet-rich thrombus superimposed on
      an atherosclerotic plaque or by atherothrombotic plaque rupture in a carotid or
      intracranial artery. Despite advances made through ultrasound imaging in our
      understanding of atherosclerotic plaque progression and regression, the issue of
      whether differences in plaque structure alone can distinguish between lesions
      that become symptomatic and others that remain clinically silent continues to be
      debated. Recent biochemical and imaging studies have identified characteristics
      that may reflect a high risk of vulnerability, such as outward, abluminal plaque
      remodelling, the presence of intra-plaque haemorrhage, inflammation, severe flow
      disturbances around the encroaching lesion, plaque cap thinning and ulceration,
      and abnormal plaque motion. Plaque stability may be improved through management
      of traditional cardiovascular risk factors or with biological or pharmacological
      agents that target pathways involved in plaque pathophysiology. Unstable plaques
      place patients at risk of unpredictable ischaemic events and in patients with
      such lesions, specific preventive treatment beyond long-term antiplatelet therapy
      can be used to prevent new or recurrent events.

PMID- 14730255
TI  - Advances in penumbra imaging with MR.
AB  - The concept of the ischaemic penumbra as critically hypoperfused and functionally
      impaired, but potentially viable brain, was introduced over 25 years ago. Recent
      studies have used a combination of perfusion-weighted magnetic resonance imaging
      (PWI) and diffusion-weighted imaging (DWI) to delineate the putative penumbra.
      PWI provides semiquantitative cerebral blood flow imaging and DWI is an index of
      the largely irreversible ischaemic core. PWI > DWI mismatch is an operational
      definition of the penumbra that was introduced in the late 1990s. This definition
      has been modified in recent years with the recognition that the PWI boundary
      includes a region of benign oligaemia and that a portion of the DWI core is
      potentially salvageable with rapid reperfusion. An MRI penumbral signature is
      present in the majority of patients within 6 h of stroke onset, often but not
      invariably associated with proximal arterial occlusion on magnetic resonance
      angiography, and is strictly time dependent. It has been postulated that
      penumbral imaging using MRI can provide a physiological 'tissue clock' and be
      used to predict benefit from thrombolytic therapy beyond the established 3-hour
      window. This has been suggested by pilot studies, but confirmation will rely on
      ongoing, prospective, randomized trials. The presence and extent of the penumbra
      may also predict the opportunity for tissue salvage with neuroprotection
      strategies. DWI and PWI parameters are being used in proof-of-principle stroke
      trials. Such trials can be performed with 100-200 patients randomized between
      treated and control groups and provide a biological signal of efficacy with only
      10% of the sample size required for a Phase III study.

PMID- 14730256
TI  - Imaging viable brain tissue with CT scan during acute stroke.
AB  - Viability of the cerebral parenchyma is dependent on cerebral blood flow (CBF).
      The assessment of cerebral perfusion in patients with acute stroke, in a
      clinically relevant time frame, could be of utmost importance for patient
      selection before thrombolytic therapy. In individual patients, quantitative
      mapping of CBF to indicate the severity and potential reversibility of neuronal
      damage can be used to predict which brain tissue will be salvaged with
      reperfusion or die without it (penumbra), as well as which brain tissue is
      already infarcted. Recent investigations of perfusion CT have shown major
      advances in the assessment of acute stroke patients. Perfusion CT offers a number
      of practical advantages over other cerebral perfusion imaging methods as it can
      be performed immediately after unenhanced CT, and used, in general, to exclude
      cerebral haemorrhage. It is fast (typical procedure time <5 min) and does not
      require specialized computer hardware. The accuracy of cerebral perfusion maps
      has been demonstrated for normal and decreased CBF value by comparison with xenon
      CT used as a gold standard. Perfusion CT infarct and penumbra maps provide a
      potential recuperation ratio (PRR) (or Lausanne Stroke Index), defined as PRR =
      penumbra/ (penumbra + infarct). This index is correlated with the improvement of
      the National Institutes of Health Stroke Scale (NIHSS) in case of arterial
      recanalization. Also, the size of the ischaemic area (infarct + penumbra) is
      correlated with the NIHSS score on hospital admission. Further studies may
      demonstrate the use of perfusion CT for the assessment of penumbra dynamics in
      function-specific brain areas. Perfusion CT is now ready to be used in clinical
      trials as a decision-making tool to tailor more precisely the thrombolytic
      therapy to the individual patient.

PMID- 14730257
TI  - Towards a new mapping of brain cortex function.
AB  - The aim of imaging neuroscience is to describe the functional organization of
      human brain at the level of large neuronal groupings, networks and systems. The
      systems level of description addresses how integrated brain functions are
      embodied in the physical structure of the brain. Magnetic resonance imaging is
      currently the technique of choice for the study of cerebral structure-function
      relationships and the analysis of structural and functional brain images can now
      be carried out automatically using statistical parametric mapping. The resultant
      ability to perform clinical-functional-anatomical correlative studies with
      complete objectivity and unparalleled sensitivity is providing powerful new
      opportunities for studying the relationship between structure and function, and
      how these parameters interact with pathology. One of the most exciting and
      dramatic observations to come from human brain mapping has been the dynamic
      plasticity of function in both normal brains and the brains of patients with
      neurological and neuropsychiatric disorders. Recent activation studies have
      provided interesting information about the brain's capacity to reorganize after
      injury and in association with practice and learning. The emerging studies of
      brain plasticity and its modulation by drugs and other therapies indicate
      potentially useful approaches to the rehabilitation of adults with brain damage,
      including damage resulting from cerebral ischaemia. Brain maps must therefore be
      viewed as dynamic, changing with development, disease progression, normal
      learning and in parallel with the recovery of function after acute injury. The
      dynamic plasticity of functional brain maps provides an exciting opportunity to
      study these processes.

PMID- 14730259
TI  - Ultrasound of the thyroid and parathyroid glands.
AB  - Ultrasound plays a prominent role in the management of thyroid disease and
      parathyroid adenomas. It can detect clinically impalpable thyroid nodules and
      characterize them as cystic, solid, or complex. Determining that a nodule is
      definitively benign or malignant is difficult, and so when indicated an
      ultrasound-guided fine-needle aspiration can be performed. In the follow-up of
      patients with thyroid cancer, ultrasound can be used alone or in conjunction with
      computed tomography (CT)/magnetic resonance imaging (MRI) to detect recurrent
      disease. Recurrences can be confirmed using ultrasound to guide fine-needle
      aspirations. To locate parathyroid adenomas, ultrasound is often used in
      conjunction with sestamibi scanning. If both studies agree on the location of the
      adenoma, the surgeon can perform focused surgery for its removal. In patients in
      whom the studies do not agree or in whom they do not detect the adenoma, further
      evaluation with CT or more preferably MRI is indicated.

PMID- 14730260
TI  - Ultrasound of the thyroid and parathyroid glands: controversies in the diagnosis
      of thyroid cancer.

PMID- 14730261
TI  - Color Doppler sonography of uterine disorders.
AB  - Color Doppler sonography (CDS) of uterine disorders has clinical applications for
      the evaluation of uterine fibroids, polyps, and vascular malformations. This
      review describes and illustrates these applications as well as the use of 3D CDS.

PMID- 14730262
TI  - Carotid artery stenosis: grayscale and Doppler ultrasound diagnosis--Society of
      Radiologists in Ultrasound consensus conference.
AB  - The Society of Radiologists in Ultrasound convened a multidisciplinary panel of
      experts in the field of vascular ultrasonography (US) to come to a consensus
      regarding Doppler US for assistance in the diagnosis of carotid artery stenosis.
      The panel's consensus statement is believed to represent a reasonable position on
      the basis of analysis of available literature and panelists' experience. Key
      elements of the statement include the following: First, all internal carotid
      artery (ICA) examinations should be performed with grayscale, color Doppler, and
      spectral Doppler US. Second, the degree of stenosis determined at grayscale and
      Doppler US should be stratified into the categories of normal (no stenosis), less
      than 50% stenosis, 50 to 69% stenosis, > or =70% stenosis to near occlusion, near
      occlusion, and total occlusion. Third, ICA peak systolic velocity (PSV) and the
      presence of plaque on grayscale and/or color Doppler images are primarily used in
      the diagnosis and grading of ICA stenosis. Two additional parameters (the ICA-to
      common carotid artery PSV ratio and ICA end diastolic velocity) may also be used
      when clinical or technical factors raise concern that ICA PSV may not be
      representative of the extent of disease. Fourth, ICA should be diagnosed as
      normal when ICA PSV is less than 125 cm/second and no plaque or intimal
      thickening is visible, less than 50% stenosis when ICA PSV is less than 125
      cm/second and plaque or intimal thickening is visible, 50 to 69% stenosis when
      ICA PSV is 125 to 230 cm/second and plaque is visible, > or =70% stenosis to near
      occlusion when ICA PSV is more than 230 cm/second and visible plaque and lumen
      narrowing are seen, near occlusion when there is a markedly narrowed lumen on
      color Doppler US, and total occlusion when there is no detectable patent lumen on
      grayscale US and no flow on spectral, power, and color Doppler US. Fifth, the
      final report should discuss velocity measurements and grayscale and color Doppler
      findings. Study limitations should be noted when they exist. The conclusion
      should state an estimated degree of ICA stenosis as reflected in these
      categories. The panel also considered various technical aspects of carotid US and
      methods for quality assessment, and identified several important unanswered
      questions meriting future research.

PMID- 14730263
TI  - Introduction.

PMID- 14730264
TI  - Advances in the laboratory diagnosis of viral respiratory disease.
AB  - BACKGROUND: In recent years significant advances in the laboratory diagnostics
      available to detect respiratory viral infections have been achieved. METHODS:
      This article presents the types of diagnostic methods currently available to the
      practitioner, as well as those on the horizon. The article covers tissue culture,
      serology and direct examination as well as some rapid diagnostic techniques and
      molecular assays, previewing developing new technology. CONCLUSIONS: Laboratory
      diagnosis will likely be clinically useful in some but not all cases of viral
      infection. As new diagnostic methods become widely available, it is increasingly
      important to develop guidelines for laboratory testing when viral illness is
      suspected.

PMID- 14730265
TI  - National disease burden of respiratory viruses detected in children by polymerase
      chain reaction.
AB  - BACKGROUND: The epidemiology of community-acquired respiratory viruses at the
      Children's Hospital of Wisconsin between 1996 and 1998 was examined with
      molecular [multiplex (M) PCR] and standard virologic methods. METHODS AND
      RESULTS: A total of 3325 patients with lower respiratory infection (LRI)
      [bronchiolitis (42%), pneumonia (38%) and croup (12%)] were identified. It is
      estimated that 545,000 LRI hospitalizations occur each year in the United States
      in children younger than 18 years old (viral, 428,000; pneumonia, 221,000;
      bronchiolitis, 222,000; croup, 65,000), including a continued increase in
      bronchiolitis hospitalizations (47.8/1000; <1 year). The most common viruses
      detected each year in hospitalized children included respiratory syncytial virus
      (A and B; 117,000), parainfluenza virus (PIV-1 and -2, 48 000; PIV-3, 18,000) and
      influenza (A and B, 39,000). With multiplex reverse transcription polymerase
      chain reaction (MPCR), different patient populations demonstrated different LRI
      epidemiology in relation to specific syndromes and viral causes. At least 21% of
      LRI hospitalizations were in children with significant medical problems.PIVs were
      detected much more frequently in immunocompromised children than in previously
      healthy children (33% vs. 16%). Similarly 15% of respiratory syncytial virus was
      detected between May and October, mostly in immunocompromised children. Influenza
      caused 19% of bronchiolitis in previously healthy children, and no virus could be
      reliably predicted based on clinical presentation, including wheezing. Of
      children hospitalized for LRI, 40% tested positive for the seven most common
      respiratory viruses by MPCR. CONCLUSIONS: Work is under way to expand the number
      of viruses detected by MPCR and to determine whether newly discovered viruses,
      such as human metapneumovirus, contribute to the burden of pediatric LRI
      hospitalizations.

PMID- 14730266
TI  - Antigenic and genetic variation in human respiratory syncytial virus.
AB  - BACKGROUND: Human respiratory syncytial virus (HRSV) is a leading cause of
      serious pediatric respiratory disease worldwide. Natural infection provides only
      partial protection as repeat infections occur throughout life. A brief review of
      the extent of antigenic and genetic variation observed in HRSV clinical isolates
      is presented. METHODS AND RESULTS: Recent experimental research is reviewed,
      describing key factors that may explain the ability of HRSV to cause multiple
      infections in the same individual even in the presence of an existing immune
      response. It is well-appreciated that variability of the G protein, both between
      and within antigenic subgroups A and B, is partially responsible for repeat HRSV
      infections. A high level of nucleotide change resulting in amino acid change
      provides strong evidence for selective pressure for change in G sequences, thus
      new HRSV variants. Although little variation in gene-coding sequences is observed
      in the F protein (the second major protective antigen), new evidence of genetic
      variation has identified alteration of gene expression levels by selection of
      changes in the gene end termination signal that precedes the gene encoding the F
      protein. Due to obligatory sequential transcription, these changes affect
      downstream gene expression levels. These data suggest that modulation of F
      protein levels may provide a selective advantage in the presence of a preexisting
      immune response. CONCLUSIONS: Experimental data in HRSV demonstrate that
      variation exists not only in gene-coding sequences but also in the signals that
      control gene expression. Thus alteration in the expression of key proteins
      provides a second type of antigenic "variation." A better understanding of these
      differences is critical to the development of an effective vaccine.

PMID- 14730267
TI  - Clinical impact and diagnosis of human metapneumovirus infection.
AB  - BACKGROUND: Acute respiratory infections are the most common illnesses
      experienced by people of all ages worldwide. A portion of hitherto unexplained
      viral respiratory tract illnesses (RTIs) can now be attributed to the human
      metapneumovirus (hMPV), which was discovered in 2001. Several surveys on the
      burden of disease of hMPV infection have been conducted in various study groups
      and with different diagnostic assays. To estimate the impact of hMPV infection in
      a hospital setting and in the community at large, we reviewed these surveys to
      establish the burden of disease of hMPV infection. METHODS: Published data and
      our own additional unpublished data on the clinical impact of hMPV infection were
      reviewed. RESULTS AND CONCLUSION: Worldwide, hMPV infections account for at least
      5 to 7% of the RTI in hospitalized children, but immunocompromised and elderly
      individuals are also at risk. In the general community hMPV infections account
      for at least 3% of patients who visit a general practitioner for RTI. The
      seasonality of hMPV infections resembles that for respiratory syncytial virus and
      influenza virus infections, with recurrent epidemics during the winter months.
      Clinical symptoms and laboratory findings associated with hMPV infection exhibit
      a spectrum virtually indistinguishable from those associated with respiratory
      syncytial virus disease. The development of diagnostic assays must take into
      account the existence of two hMPV serotypes.

PMID- 14730268
TI  - Predisposition of infants with chronic lung disease to respiratory syncytial
      virus-induced respiratory failure: a vascular hypothesis.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) causes the highest rate of severe
      respiratory infections and mortality in infants and children worldwide. Preterm
      infants with underlying chronic lung disease (CLD), including bronchopulmonary
      dysplasia (BPD), are among those at high risk for severe morbidity, long term
      sequelae and mortality postinfection. The definition of CLD/BPD has evolved and
      is currently described as a disease of restricted lung development (i.e. impaired
      alveolar and pulmonary vascular development). This article describes potential
      mechanisms by which RSV infection causes respiratory failure in the infant with
      BPD. METHODS AND RESULTS: The opinions expressed in this article are based on a
      review of recent investigations into the mechanisms through which RSV infections
      could cause excessive pulmonary edema formation and subsequent respiratory
      failure in the infant with CLD. Although alveolar overinflation and atelectasis
      are well-described patterns of RSV-induced respiratory illness in this infant
      population, the finding of pulmonary edema is a complex, multifactorial process
      that is less well understood. Experimental evidence suggests that RSV infection
      in infants with CLD/BPD not only causes increases in pulmonary vascular
      reactivity but also precipitates pulmonary edema formation via multiple
      mechanisms (e.g. nonuniform elevations in pulmonary artery pressure, endothelial
      injury, alveolar epithelial damage and impairments of native alveolar liquid
      clearance mechanisms). CONCLUSIONS: Novel therapies for managing RSV-induced
      respiratory failure in the infant with CLD/BPD must consider factors responsible
      for the substantial pulmonary vascular component of this illness.

PMID- 14730269
TI  - Physiologic risk factors for respiratory viral infections and immunoprophylaxis
      for respiratory syncytial virus in young children with congenital heart disease.
AB  - BACKGROUND: Infants and children with congenital heart disease (CHD) are a
      population at increased risk for infection with respiratory syncytial virus (RSV)
      and its inherent complications compared with the general population. RSV
      infection increases morbidity from respiratory complications in young CHD
      patients. METHODS: In an effort to guide strategies for reducing RSV-associated
      risk in patients with CHD, predisposing factors for severe RSV as well as
      experimental approaches for prevention were reviewed. CONCLUSIONS: Risk factors
      that may exacerbate the adverse effects of respiratory disease in young CHD
      patients include compromised cardiorespiratory status at baseline, altered
      pulmonary mechanics, potential cyanosis and/or pulmonary hypertension and
      ventilation-perfusion mismatch. Furthermore patients with such conditions are at
      increased risk from RSV lower respiratory tract infection, making RSV prevention
      in patients with CHD an important goal. Because the efficacy and safety of active
      immunization for RSV have not yet been established, a number of approaches toward
      passive immunoprophylaxis have been investigated. Monthly prophylaxis with
      palivizumab, a humanized murine monoclonal anti-F glycoprotein antibody
      preparation, reduced the rate of hospitalization in children with CHD by 45%, as
      well as hospital time and oxygen use in those admitted. Thus palivizumab
      prophylaxis should be considered in young patients with hemodynamically
      significant CHD.

PMID- 14730271
TI  - Occurrence of respiratory virus: time, place and person.
AB  - BACKGROUND: Respiratory viruses account for most respiratory infections. Although
      analysis of epidemiologic information regarding viral seasonality, sites of
      transmission and susceptible populations is essential to devising strategies for
      limiting epidemics, few long term epidemiologic studies have addressed these
      questions. METHODS: Epidemiologic findings identifying susceptible populations,
      as well as temporal and geographic patterns of infection with influenza virus,
      respiratory syncytial virus, rhinovirus and parainfluenza virus were reviewed.
      CONCLUSIONS: Influenza is the virus most frequently associated with outbreaks of
      respiratory infection resulting in medical consultation as well as virus-related
      lethality. Similar symptom profiles and overlapping seasonality of respiratory
      syncytial virus and other viruses may sometimes complicate surveillance and
      treatment. Although vaccination and antiviral drugs are virus-specific, factors
      that promote transmission and thus strategies for limiting outbreaks are similar
      for various respiratory viruses.

PMID- 14730270
TI  - Contribution of respiratory syncytial virus G antigenicity to vaccine-enhanced
      illness and the implications for severe disease during primary respiratory
      syncytial virus infection.
AB  - BACKGROUND: Immunization of BALB/c mice with vaccinia virus expressing the G
      glycoprotein (vvG) of respiratory syncytial virus (RSV) or with formalin
      inactivated alum-precipitated RSV (FI-RSV) predisposes for severe illness, type 2
      cytokine production and pulmonary eosinophilia after challenge with live RSV.
      This similar disease profile has led to the proposal that the presence of the G
      glycoprotein in the FI-RSV preparation was the immunologic basis for the vaccine
      associated enhancement of disease observed in the failed clinical trials of the
      1960s. However, processes of disease pathogenesis observed in FI-RSV- and vvG
      immunized mice suggest that FI-RSV and vvG immunizations induce immune responses
      of different compositions and requirements that converge to produce similar
      disease outcomes upon live virus challenge. METHODS: The potential role of RSV G
      present in FI-RSV preparations in increasing postimmunization disease severity
      was explored in mice. RESULTS: The absence of RSV G or its immunodominant epitope
      during FI-RSV immunization does not reduce disease severity after RSV challenge.
      Furthermore although depletion of V beta 14+ T cells during RSV challenge
      modulates disease in G-primed mice, minimal impact on disease in FI-RSV-immunized
      mice is observed. CONCLUSION: FI-RSV vaccine-enhanced illness is not attributable
      to RSV G. Furthermore formulation of a safe and effective RSV vaccine must ensure
      RSV antigen production, processing and presentation via the endogenous pathways.
      Thus gene delivery by vector, by DNA or by live attenuated virus are attractive
      vaccine approaches.

PMID- 14730272
TI  - The future of respiratory syncytial virus vaccine development.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of viral lower
      respiratory tract illness in infants and children and is an important cause of
      lower respiratory tract illness in other populations. Despite decades of research
      there are currently no licensed vaccines for prevention of RSV disease. METHODS:
      A review of the obstacles to RSV vaccine development; current live, attenuated
      and subunit RSV vaccines in clinical development; and the potential for
      developing additional vaccine candidates based on recombinant technology.
      RESULTS: A number of biologically derived live attenuated RSV vaccines were
      evaluated in Phase I clinical trials in adults and children, and one vaccine
      (cpts 248/404) was evaluated in infants as young as 1 month of age. These
      vaccines displayed a spectrum of attenuation, with cpts 248/955 being the least
      attenuated and cpts 248/404 being the most attenuated candidate vaccine. None of
      these was sufficiently attenuated for young infants. The ability to generate
      recombinant RSV vaccines has led to the development of large numbers of candidate
      vaccines containing combinations of known attenuating point mutations and
      deletions of nonessential genes. Clinical evaluation of many of these candidates
      is in progress. Three types of RSV subunit vaccines have recently been evaluated
      in clinical trials: purified F glycoprotein vaccines (PFP-1, PFP-2 and PFP-3),
      BBG2Na and copurified F, G and M proteins. Additional studies of the F/G/M
      protein vaccine are being conducted. CONCLUSIONS: During the past 10 years,
      considerable progress has been made in RSV vaccine development. It is likely that
      different RSV vaccines will be needed for the various populations at risk.

PMID- 14730273
TI  - Vaccination for pandemic influenza: a six point agenda for interpandemic years.
AB  - BACKGROUND: The demand for influenza vaccine is driven by recognition of its
      health and economic benefits. Vaccine reduces all cause mortality in the elderly
      by 30 to 50% and prevents > or =30% of hospital admissions for influenza-related
      respiratory disease, heart disease and stroke. However, because most influenza
      vaccine (85%) is produced in only eight countries, adequate production and
      equitable distribution of vaccine throughout the world will pose a serious
      challenge when the next influenza pandemic appears. METHODS: This article reviews
      a six point agenda for pandemic vaccination that should be undertaken during
      interpandemic years. The agenda includes preparing vaccine seed strains using
      reverse genetics, determining the characteristics of a pandemic vaccine and
      vaccination schedule, considering global registration of pandemic vaccines,
      increasing vaccination in interpandemic years, documenting the epidemiology of
      vaccine use and addressing political issues that will affect the global supply of
      pandemic vaccines. CONCLUSIONS: Planning for pandemic vaccination must begin
      during the interpandemic period to ensure a vaccine supply that will be adequate
      to meet demand in all countries. This will require the skills not only of experts
      in virology, epidemiology and public health but also those in politics, economics
      and law. The task will be complex, but its promised benefits will be immense.

PMID- 14730274
TI  - Viral respiratory infection and the link to asthma.
AB  - BACKGROUND: Acute wheezing secondary to viral infection is common in children.
      Whereas many children suffer primarily mild to moderate symptoms, others develop
      severe coughing and wheezing. METHODS: Review of recent medical literature
      regarding the correlation between viral illness and increased susceptibility to
      develop severe respiratory illnesses and subsequent asthma. DISCUSSION: In
      infants factors that predispose to severe disease and lower respiratory airway
      effects include small lung size, passive smoke exposure, virus-induced immune
      responses, severe disease and infection at a young age. Acute asthma symptoms
      have been correlated with a variety of viral pathogens, most commonly respiratory
      syncytial virus bronchiolitis in infancy and rhinovirus in older children.
      Epidemiologic and biologic factors that influence development of asthma include
      repeated exposure to infectious disease during early childhood, early exposure to
      pets, a farming lifestyle, alterations in bacterial flora of the intestine and
      increased use of antibiotics. Thus the likelihood of asthma is related to the
      specific pathogen, severity of infection, cumulative number of infections and
      stage of immunologic development. Progress is also being made in understanding
      how viruses can adversely affect lung or immune development. In asthmatic
      children viral infections initiate bronchospasm and airway obstruction. It is
      hoped that research on virus-induced airway alterations and the host factors that
      lead to severe clinical illnesses can help clinicians to identify children whose
      wheezing is an early sign of asthma.

PMID- 14730276
TI  - [Clinical and embryological approaches to nasal dermoid sinus cysts].
AB  - Nasal dermoid sinus cyst (NDSC) is an uncommon congenital lesion presenting as a
      large panel of midline craniofacial anomalies. Thirty children with nasal midline
      masses and/or sinus ostia were surgically treated in the pediatric ENT and
      cervicofacial surgery department of Trousseau's children's hospital (Paris
      France) between 1995 and 2002. All our patients underwent radiological evaluation
      including CT scan (including axial and coronal planes) and/or MRI (in all three
      planes) in search of intracranial extension. Thirteen of our patients presented
      with a midline cyst only, ten had nasal pit only, and seven had combined
      anomalies. Preoperative radiology and surgery showed an intracranial extension in
      3 patients, which exhibited contact of the cyst with the dura. Recurrence being
      expected if any dermal tissues were left in place, "one-time-excision management"
      was the rule. CT and MR imaging features were reviewed. The external rhinoplasty
      procedure resulted in a wide surgical approach, low recurrence and good esthetic
      results. The embryological and anatomical origins of NDSCs are reviewed.
      Development of NDSC during embryological development implicates two necessary and
      sufficient conditions: competence of the ectodermal and mesectodermal cells to
      form dermoid tissue with epithelial-mesenchymal interactions, and a topographical
      site of ectodermal inclusion, which fits well with the various clinical
      presentations of NDSCs. We propose to distinguish NDSCs of anterior topography,
      located at the anterior skull base level from the basal NDSCs, located at the
      middle skull base level. We reviewed the various localizations of NDSCs,
      revisiting a forgotten embryological theory, which unify the various clinical
      localizations of anterior NDSCs.

PMID- 14730275
TI  - Respiratory viruses predisposing to bacterial infections: role of neuraminidase.
AB  - BACKGROUND AND METHODS: Viral-bacterial coinfections in humans are well
      documented. Viral infections often lead to bacterial superinfections. In vitro
      and animal models for influenza, as well as molecular microbiology study of
      viruses and bacteria, provide an understanding of the mechanisms that explain how
      respiratory viruses and bacteria combine to cause disease. This article focuses
      on viral and bacterial combinations, particularly synergism between influenza and
      Streptococcus pneumoniae. RESULTS: Potential mechanisms for synergism between
      viruses and bacteria include: virus destruction of respiratory epithelium may
      increase bacterial adhesion; virus-induced immunosuppression may cause bacterial
      superinfections; and inflammatory response to viral infection may up-regulate
      expression of molecules that bacteria utilize as receptors. Influenza and
      parainfluenza viruses possess neuraminidase (NA) activity, which appears to
      increase bacterial adherence after viral preincubation. Experimental studies
      demonstrate that viral NA exposes pneumococcal receptors on host cells by
      removing terminal sialic acids. Other studies show that inhibition of viral NA
      activity reduces adherence and invasion of S. pneumoniae, independently of
      effects on viral replication. Clinical studies reveal that influenza vaccination
      reduces the incidence of secondary bacterial respiratory tract infections.
      CONCLUSIONS: Detection of viral factors (e.g. high NA activity) that increase the
      likely potential of epidemic/pandemic influenza strains for causing morbidity and
      mortality from secondary bacterial infections provides new possibilities for
      intervention. Additional study is needed to identify the mechanisms for the
      development of bacterial complications after infections with respiratory
      syncytial virus and other important respiratory viruses that lack NA activity.
      Prevention of bacterial superinfection is likely to depend on effective antiviral
      measures.

PMID- 14730277
TI  - [Trigeminal neuralgia: results of microsurgical and endoscopic-assisted vascular
      decompression].
AB  - INTRODUCTION: Vascular compression of the Vth cranial nerve is the leading cause
      of trigeminal neuralgia. Microvascular decompression has been promoted by
      Jannetta since 1970. We used the minimally invasive retrosigmoid approach, with
      the complementary help of endoscopic procedure. OBJECTIVES: MRI results, surgical
      findings and pain relief were studied after endoscopic assisted microvascular
      decompression. MATERIAL AND METHODS: Between 1991 and 2000, 98 surgeries were
      performed on 79 patients unresponsive to medical treatment, after an average of 6
      years from the onset of the disorder. The mean follow-up period after operation
      was 28 months. RESULTS: MRI predicted neurovascular conflict with sensitivity of
      93.6% and specificity of 100%. Pain relief after surgery was complete in 69% of
      the cases, partial in 21%. Surgery was a failure in 6% of the cases and 4% of
      patients were lost. Complications were limited to 10% of CSF disorders but only
      1% (1 patient) needed a surgical revision. CONCLUSION: Microvascular
      decompression, performed through a key-hole approach, without cerebellum
      retraction and with endoscopic assisted surgery, yields a low risk of morbidity,
      even in elderly patients, and could be considered acceptable causal treatment of
      trigeminal neuralgia.

PMID- 14730278
TI  - [Adrenal insufficiency after treatment of nasal polyposis].
AB  - OBJECTIVE: Assessment of hypothalamic-pituitary-adrenal (HPA) axis after long
      term and uncontrolled corticosteroid treatment in nasal polyposis. PATIENTS AND
      METHODS: A short synacthen test was performed in ten patients who received
      uncontrolled doses of corticosteroids in a population of 128 patients treated for
      nasal polyposis. RESULTS: Mean yearly dose of oral prednisone administered in
      short-term treatment varied between 1280 and 7300 mg. Mean daily dose of inhaled
      beclomethasone varied between zero and 2000 microg. Morning plasmatic cortisol
      was abnormal in seven the patients before and after the stimulation (respectively
      140 nmole/l and 359 nmole/l). DISCUSSION: High and uncontrolled doses of
      corticosteroids in nasal polyposis affect HPA axis.

PMID- 14730279
TI  - [Preliminary analysis of sentinel node detection during surgical treatment of
      head and neck melanoma].
AB  - OBJECTIVE: The aim of this study was to define reliability of the sentinel lymph
      node technique in head and neck N0 melanoma. Identification of the sentinel node,
      which is the first evidence of melanoma metastasis, enables selective node
      dissection. MATERIALS AND METHODS: Twelve patients with untreated localized
      cutaneous or mucous N0 melanoma of the head and neck were included in this study.
      After resection of the sentinel lymph node, type III neck dissection was
      performed during the same operative time in all twelve patients. RESULTS: The
      sentinel node was successfully located by preoperative lymphoscintigraphy and
      confirmed at surgery in eleven patients. Five of these patients had evidence of
      metastatic node disease, always in the sentinel node. No other metastatic node
      were found in the neck dissection specimens. For the six other patients with a
      negative sentinel node, no other metastatic node was found in the neck dissection
      specimens. CONCLUSION: These preliminary results are promising. The sentinel node
      can be mapped and identified in most patients. No metastatic node was noted in
      patients with a negative sentinel node. If these results are confirmed, complete
      node dissection should only be performed in patients with a positive sentinel
      node in order to achieve more conservative surgical cure of head and neck
      melanoma.

PMID- 14730280
TI  - [Lips reanimation with temporalis myoplasty technique].
AB  - PURPOSE OF THE STUDY: The authors report their experience in lips reanimation
      with lengthening temporalis myoplasty for treatment of facial paralysis.
      MATERIALS AND METHODS: We studied 8 patients with permanent facial paralysis. The
      surgical technique allowed to transfer temporalis tendinous of coronoid process
      onto lips muscular strap, without aponevrotic relay. RESULTS: Functional and
      aesthetic results are exposed and so complications. Specialized facial
      physiotherapy rehabilitation is necessary in order to improve.

PMID- 14730281
TI  - [Granular cell tumor of the cervical esophagus: a case report].
AB  - BACKGROUND: Granular cell tumor of the cervical esophagus is a rare and benign
      tumor. We present a case of constricting granular cell tumor of the cervical
      esophagus and discuss esophageal reconstruction. CASE REPORT: Constricting
      granular cell tumor of the cervical esophagus was diagnosed in a patient who
      experienced aphagia for two years. Endoscopy demonstrated complete stricture of
      the cervical esophagus and computed tomography and magnetic resonance imaging
      confirmed the presence of a tumor formation in the cervical esophagus. Total
      esophagectomy with preservation of the larynx was performed. DISCUSSION: Surgical
      treatment raises the problem of esophageal reconstruction (gastric pull up, free
      flap reconstruction). We used the gastric pull up technique and fashioned a
      piriform sinus anastomosis. There was no postoperative complication and
      functional outcome was excellent. CONCLUSION: Computed tomography and magnetic
      resonance imaging provide essential data on the spread and location of granular
      cell tumor. Surgery provides excellent functional results.

PMID- 14730282
TI  - [Myospherulosis of the maxillary sinus].
AB  - BACKGROUND: We present a case of a myospherulosis, describe the underlying cause
      and discuss ways of preventing its development. CASE REPORT: A 35-year-old man
      presented myospherulosis of the maxillary sinus caused by an antibiotic ointment
      placed in the sinus three years earlier during a Caldwell Luc procedure. The
      patient underwent a second Calwell Luc procedure. Outcome was uneventful and no
      recurrence was noted. DISCUSSION: Histological examination should be ordered at
      reoperation and petroleum-based ointments and packings should be avoided in sinus
      surgery.

PMID- 14730284
TI  - Marshall Parks lecture. Binocular sensory outcomes in accommodative ET.
AB  - PURPOSE: To review what is known about the normal maturational sequence for
      fusion and stereopsis and the binocular sensory deficits associated with
      accommodative esotropia (ET) and to explore the clues that accommodative ET
      provides about critical periods for binocular sensory function. METHODS: Studies
      of binocular sensory function during infancy and early childhood are presented.
      RESULTS: Most of the maturation of binocular sensory function occurs during the
      first year of life, yet a later abnormal visual experience-such as the onset of
      accommodative ET--can profoundly and permanently disrupt fusion and stereopsis.
      CONCLUSIONS: Some binocular sensory deficits may exist before the onset of
      accommodative ET, but others may result directly from abnormal binocular
      experience. The functional organization of the maturing visual system appears to
      be maximally sensitive to disruption by abnormal visual experience during the
      first months of life, but susceptibility continues until at least 4 years of age.

PMID- 14730285
TI  - Pediatric ophthalmology and strabismus in Sweden.

PMID- 14730286
TI  - Report of the XV Congress of the Latin American Council of Strabismus.

PMID- 14730288
TI  - Pediatric airbag-associated ocular trauma and endothelial cell loss.
AB  - BACKGROUND: Airbag-associated ocular trauma among the adult population has been
      widely reported, but reports of these injuries in children are sparse. Laboratory
      experiments suggest that airbag-associated ocular trauma may cause endothelial
      cell loss, but reports of in vivo human endothelial cell counts are anecdotal.
      METHODS: A retrospective chart review was performed of all patients with airbag
      associated ocular trauma at a pediatric hospital from 1995 to 2001. From 2001 to
      2002, endothelial cell counts were obtained from 9 eyes of airbag-associated
      ocular trauma subjects and 22 eyes of control subjects. RESULTS: Sixteen patients
      were identified; all had periocular abrasions, edema, and/or ecchymosis. Other
      ocular injuries included corneal abrasions (n = 9 or 56%), corneal edema (n = 8
      or 50%), hyphema (n = 7 or 44%), lens opacities (n = 5 or 31%), and macular scars
      (n = 2 or 12%). Three eyes of three patients required intraocular surgery.
      Unilateral visual loss (hand-motions, 20/100) occurred in two patients. A
      decrease in mean endothelial cell count of 547 cell/mm2 (P =.01) was found in the
      airbag-associated ocular trauma group eyes when compared with control group eyes.
      CONCLUSIONS: The present study includes the largest reported case series of
      pediatric airbag-associated ocular trauma. Airbag-associated ocular trauma may
      necessitate intraocular surgery, may result in permanent visual loss, and may
      cause endothelial cell loss in pediatric patients.

PMID- 14730289
TI  - Anterior vitreous face behavior with AcrySof in pediatric cataract surgery.
AB  - PURPOSE: To describe anterior vitreous face behavior when AcrySof (Alcon, Fort
      Worth, TX) intraocular lenses come in contact with the anterior vitreous face
      after posterior continuous curvilinear capsulorhexis without anterior vitrectomy
      in pediatric patients undergoing cataract surgery. METHODS: This study comprised
      14 eyes of 12 children whose mean age was 9.6 years (range, 2.3 to 16.0). All
      eyes underwent primary posterior continuous curvilinear capsulorhexis without
      anterior vitrectomy and had AcrySof IOLs implanted in the bag. Changes on the
      anterior vitreous face were documented, and visual acuity was recorded.
      Statistical analysis was performed using Student group t and Mann Whitney tests.
      RESULTS: Mean length of follow-up was 21.1 +/- 7.4 months (range, 15.0 to 36
      months). Nine eyes (64.3%) had a clear visual axis, whereas 5 eyes (35.7%)
      developed anterior vitreous face changes. Of those with anterior vitreous face
      changes, 60% (3 of 5) eyes showed a fine meshwork-like reticular response termed
      "anterior vitreous reticular response" (AVR); 20% (1 of 5) eyes showed a scaffold
      response; and 20% (1 of 5) eyes showed a mixed response at the last follow-up
      examination. The difference in visual acuity before and after the development of
      the AVR response was not significant (P =.712). The mean age of patients with
      eyes having a clear visual axis was 12.1 +/- 2.3 years (median = 11.0; range, 9.1
      to 16.0), and the mean age of patients with eyes having anterior vitreous face
      changes was 5.1 +/- 3.4 years (median = 3.6; range, 2.3 to 11.6) (P =.0098).
      CONCLUSION: The results suggest that when the AcrySof intraocular lenses come in
      contact with the anterior vitreous face, they produce the AVR response during the
      early postoperative period in younger eyes. This does not seem to have any
      significant impact on visual acuity.

PMID- 14730290
TI  - Treatment of upshoot and downshoot in Duane syndrome by recession and Y-splitting
      of the lateral rectus muscle.
AB  - BACKGROUND: Duane syndrome is characterized by abduction deficiency, narrowing of
      the palpebral fissure with retraction of globe on attempted adduction, and
      upshoot or downshoot, which can be the most prominent feature of the motility
      disorder. The upshoot and downshoot is believed to be caused by a tautness or
      leash effect from the lateral rectus muscle. The purpose of this study was to
      present the results of recession of the lateral rectus muscle with Y-splitting in
      the treatment of upshoot and downshoot in Duane syndrome. METHODS: Ten patients
      with Duane syndrome underwent surgery for severe upshoot or downshoot. Lateral
      rectus muscles recession from 5.0 to 9.0 mm and Y-splitting was accomplished in
      all patients. In 6 patients, the medial rectus muscles were recessed
      simultaneously from 5.0 to 6.0 mm to correct the associated marked globe
      retraction and ocular deviation. RESULTS: Mean age at the time of surgery was 9.9
      +/- 6.9 years (range, 3 to 20). Median follow up was 6 months (range, 3 weeks to
      3 years). After surgery, all patients showed a marked decrease in upshoot or
      downshoot as well as improvement in globe retraction and face turn, where
      present. CONCLUSIONS: Recession of lateral rectus muscle with Y-splitting is an
      extremely effective procedure in the treatment of significant upshoot and
      downshoot associated with globe retraction in Duane syndrome. When combined with
      simultaneous recession of the medial rectus muscle, it improves globe retraction
      and corrects ocular deviation.

PMID- 14730291
TI  - Threshold visual acuity testing of preschool children using the crowded HOTV and
      Lea Symbols acuity tests.
AB  - PURPOSE: To compare the testability and threshold acuity levels for very young
      children on the crowded HOTV logMAR distance visual acuity test presented on the
      BVAT apparatus and the Lea Symbols logMAR distance visual acuity chart. METHODS:
      Subjects were 87 Head Start children from age 3 to 3.5 years. Testing consisted
      of binocular pretraining at near using a lap card as needed, binocular
      pretraining at 3 m, and threshold testing for each eye. The testing procedure,
      adapted from the Amblyopia Treatment Study, presented optotypes until the child
      was unable to correctly name or match three of three or three of four optotypes
      of a given size. Threshold acuity was the smallest size for which at least three
      optotypes were correctly identified. RESULTS: Both near and distance pretraining
      were completed by 71% of children for HOTV and by 75% for Lea Symbols (P =.39).
      The distribution of threshold acuities differed between the two tests. For the 69
      eyes of 53 children who were successfully tested with both optotypes, results
      from the crowded HOTV acuity test were on average 0.25 logMar (2.5 lines) better
      than those from the Lea Symbols acuity test (P <.001). CONCLUSIONS: The
      proportion of children between 3 and 3.5 years of age whose monocular visual
      acuity could be assessed was high and was similar for the two charts tested.
      Crowded HOTV acuity results were better on average than results using Lea
      symbols. The different formats of the two tests may explain the observed
      differences in threshold acuity level.

PMID- 14730292
TI  - Intraocular lens implantation during infancy: perceptions of parents and the
      American Association for Pediatric Ophthalmology and Strabismus members.
AB  - BACKGROUND: To determine whether a randomized clinical trial, the Infant Aphakia
      Treatment Study, comparing intraocular lens (IOL) implantation with contact lens
      (CL) correction for infants with a unilateral congenital cataract (UCC), is
      feasible by (1) ascertaining whether American Association for Pediatric
      Ophthalmology and Strabismus (AAPOS) members have equipoise regarding these two
      treatments and (2) evaluating the willingness of parents to agree to
      randomization. METHODS: All AAPOS members were surveyed in August 1997 and again
      in June 2001 regarding their use of CLs and IOL implants to correct infants
      vision after unilateral cataract surgery. In addition, a pilot study was begun in
      March 2002 to evaluate the safety of IOL implantation during infancy and the
      willingness of parents to randomize their children with a UCC to either IOL
      implantation or CL correction. RESULTS: In 1997, 89% of the 260 respondents
      reported that in the previous year they had treated at least one infant with a
      UCC, but only 4% had implanted an IOL in an infant <7 months old. Silsoft (Bausch
      & Lomb, Rochester, NY) CL correction was the preferred treatment choice for 84%
      of the respondents. In 2001, 21% of the 279 respondents had implanted an IOL in
      an infant. On a scale from 1 to 10 with 1 strongly favoring an IOL implant and 10
      strongly favoring a CL, the median score was 7.5. Sixty-one percent of the
      respondents indicated that they would be willing to randomize children with a UCC
      to one of these two treatments. The main concerns about IOL implantation were
      poor predictability of power changes, postoperative complications, inflammation,
      and technical difficulty of surgery. The main concerns about CL correction were
      poor compliance, high lens loss rate, high cost, and keratitis. In our pilot
      study, 30 infants <7 months of age were evaluated at nine clinical centers for a
      visually significant UCC. Of 24 infants eligible for randomization, the parents
      of 17 (71%) agreed to randomization. CONCLUSIONS: Although most AAPOS members
      still favor CL correction after cataract surgery for a UCC, five times as many
      had implanted an IOL in an infant in 2001 compared with the number in 1997.
      Parents were almost equally divided in their preference for IOL implant versus CL
      correction. Given the relative equipoise of AAPOS members regarding these
      treatments and the willingness of more than two thirds of parents to agree to
      randomization, it seems likely that a randomized clinical trial comparing these
      two treatments could indeed be conducted.

PMID- 14730293
TI  - The accuracy of the amblyopia treatment study visual acuity testing protocol.
AB  - PURPOSE: To study the accuracy of the newly proposed Amblyopia Treatment Study
      (ATS) visual acuity testing protocol for 3- to 6-year-old children. Because no
      "gold standard" is available for acuity testing in pediatric patients, accuracy
      was evaluated using computer simulations based on a psychometric model. METHODS:
      Monte Carlo simulations of ATS acuity data were generated using a psychometric
      model that accounts for true acuity, noise in the visual system, and the rate of
      inadvertent misses. We varied true acuity from 20/15 to 20/400 (-0.1 to 1.3
      logMAR). Visual system noise was represented by the slope beta of the
      psychometric function and ranged from 1 (noisy) to 8 (not noisy). The rate of
      inadvertent misses ranged from 0% to 10%. Accuracy of the ATS protocol was
      evaluated in terms of precision, bias, and stimulus range limitations. The same
      model was fitted to experimental ATS acuity data, thus allowing us to study the
      distributions of acuity, visual system noise, and level of attentiveness in 126
      children ages 3 to <7 years. RESULTS: For conditions with little noise in the
      visual system (beta > 2), precision was well within 0.1 logMAR (corresponding to
      one line on a logMAR letter chart), except for acuities worse than 1.2 logMAR,
      and decreased to 0.15 to 0.2 logMAR for beta = 1. Bias was negligible, except in
      noisy conditions, where the ATS protocol tended to overestimate acuity by one
      line at the poor end of the true acuity range and underestimate acuity at the
      good end of the true acuity range. Effects of the rate of inadvertent misses were
      small. Fits to the real data showed a wide range of slope parameters, but only
      11% had beta < or = 2. The rate of inadvertent misses was < or = 2% in 89% of
      cases. CONCLUSION: The simulations suggest that the ATS protocol offers an
      accurate method for assessing visual acuity in children in the range of 3 to 6
      years of age with both precision and bias within 0.1 logMAR for typical values of
      the psychometric parameters.

PMID- 14730294
TI  - Intracranial infection associated with preseptal and orbital cellulitis in the
      pediatric patient.
AB  - PURPOSE: To identify risk factors in children admitted with preseptal or orbital
      cellulitis with associated intracranial infection. METHODS: A retrospective chart
      review identified 10 patients (< or = 18 years) with a diagnosis of preseptal or
      orbital cellulitis and a concurrent or subsequent diagnosis of intracranial
      infection. RESULTS: Diagnoses confirmed by imaging included sinusitis (n = 10),
      preseptal cellulitis (n = 4), orbital cellulitis (n = 6), orbital subperiosteal
      abscess (n = 5), Pott's puffy tumor (n = 4), epidural empyema (n = 2), epidural
      abscess (n = 6), and brain abscess (n = 2). The timing of diagnosis of
      intracranial infection ranged from hospital day 1 to 21. All but 1 patient had
      positive microbial cultures. Seven of 10 patients had positive microbial cultures
      from two or more sites, 70% of which were polymicrobial; Streptococcus species
      and Staphylococcus species were the most commonly isolated bacterial pathogens.
      All patients required both medical and surgical therapy; all 10 patients
      underwent sinus surgery; 8 patients required neurosurgical craniotomy; and 5
      patients underwent orbital surgery. There were no deaths. CONCLUSION:
      Intracranial involvement should be suspected in any patient age > or = 7 years
      with preseptal or orbital cellulitis associated with orbital subperiosteal
      abscess, Pott's puffy tumor, concurrent sinusitis, complaints of headache, and
      continuing fever despite intravenous antibiotics. Given the high incidence of
      polymicrobial infection found on cultures in this series, broad-spectrum
      antibiotics are strongly indicated. When imaging the orbits and sinuses in such
      patients, we recommend including the brain to rule out intracranial involvement.

PMID- 14730295
TI  - The threshold for the detection of strabismus.
AB  - PURPOSE: To identify the threshold at which horizontal or vertical strabismus
      becomes reliably detectable by observers and to determine the effects of
      interpupillary distance, age, gender, and observer experience. METHODS: Six
      models of different gender, age, and interpupillary distance were digitally
      photographed in several predetermined gaze positions off-axis in the horizontal
      and vertical planes. Standardized distance, zoom factor, and lighting were used.
      The images were digitally altered to exactly superimpose one eye deviated and one
      eye aligned with the axis of the camera. This simulated horizontal and vertical
      strabismus ranged from 2.5 to 20 prism diopters (PD). The images were arranged in
      random order and presented to groups of lay and professional observers, and their
      responses were recorded. RESULTS: The statistically significant threshold for
      detecting esotropia, exotropia, and hypertropia was 12.5 PD. Hypotropia had a
      higher threshold of 20 PD. Observer experience and model age each had a
      significant effect on the ability to detect strabismus. CONCLUSION: Our study
      demonstrates a unique method for assessing the significance of different types
      and degrees of strabismus. Our findings may be used to help patients with
      strabismus as they consider others' perception of their ocular misalignment.
      Physicians can also use this information in making decisions regarding surgery.

PMID- 14730296
TI  - Duane's retraction syndrome in association with retinitis pigmentosa.

PMID- 14730297
TI  - Retinoblastoma with cataract and ectopia lentis.

PMID- 14730299
TI  - New device: Noncrushing muscle clamp for inferior oblique recession.

PMID- 14730298
TI  - Antenatal ophthalmology.

PMID- 14730300
TI  - Intracranial hypertension secondary to all-trans retinoic acid treatment for
      leukemia: diagnosis and management.

PMID- 14730301
TI  - Comparing genomic expression patterns across species identifies shared
      transcriptional profile in aging.
AB  - We developed a method for systematically comparing gene expression patterns
      across organisms using genome-wide comparative analysis of DNA microarray
      experiments. We identified analogous gene expression programs comprising shared
      patterns of regulation across orthologous genes. Biological features of these
      patterns could be identified as highly conserved subpatterns that correspond to
      Gene Ontology categories. Here, we demonstrate these methods by analyzing a
      specific biological process, aging, and show that similar analysis can be applied
      to a range of biological processes. We found that two highly diverged animals,
      the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster,
      implement a shared adult-onset expression program of genes involved in
      mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular
      transport. Most of these changes were implemented early in adulthood. Using this
      approach to search databases of gene expression data, we found conserved
      transcriptional signatures in larval development, embryogenesis, gametogenesis
      and mRNA degradation.

PMID- 14730302
TI  - A direct functional link between the multi-PDZ domain protein GRIP1 and the
      Fraser syndrome protein Fras1.
AB  - Cell adhesion to extracellular matrix (ECM) proteins is crucial for the
      structural integrity of tissues and epithelial-mesenchymal interactions mediating
      organ morphogenesis. Here we describe how the loss of a cytoplasmic multi-PDZ
      scaffolding protein, glutamate receptor interacting protein 1 (GRIP1), leads to
      the formation of subepidermal hemorrhagic blisters, renal agenesis, syndactyly or
      polydactyly and permanent fusion of eyelids (cryptophthalmos). Similar
      malformations are characteristic of individuals with Fraser syndrome and animal
      models of this human genetic disorder, such as mice carrying the blebbed mutation
      (bl) in the gene encoding the Fras1 ECM protein. GRIP1 can physically interact
      with Fras1 and is required for the localization of Fras1 to the basal side of
      cells. In one animal model of Fraser syndrome, the eye-blebs (eb) mouse, Grip1 is
      disrupted by a deletion of two coding exons. Our data indicate that GRIP1 is
      required for normal cell-matrix interactions during early embryonic development
      and that inactivation of Grip1 causes Fraser syndrome-like defects in mice.

PMID- 14730303
TI  - Dynamics of the p53-Mdm2 feedback loop in individual cells.
AB  - The tumor suppressor p53, one of the most intensely investigated proteins, is
      usually studied by experiments that are averaged over cell populations,
      potentially masking the dynamic behavior in individual cells. We present a system
      for following, in individual living cells, the dynamics of p53 and its negative
      regulator Mdm2 (refs. 1,4-7): this system uses functional p53-CFP and Mdm2-YFP
      fusion proteins and time-lapse fluorescence microscopy. We found that p53 was
      expressed in a series of discrete pulses after DNA damage. Genetically identical
      cells had different numbers of pulses: zero, one, two or more. The mean height
      and duration of each pulse were fixed and did not depend on the amount of DNA
      damage. The mean number of pulses, however, increased with DNA damage. This
      approach can be used to study other signaling systems and suggests that the p53
      Mdm2 feedback loop generates a 'digital' clock that releases well-timed quanta of
      p53 until damage is repaired or the cell dies.

PMID- 14730304
TI  - Lamr1 functional retroposon causes right ventricular dysplasia in mice.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a hereditary cardiomyopathy
      that causes sudden death in the young. We found a line of mice with inherited
      right ventricular dysplasia (RVD) caused by a mutation of the gene laminin
      receptor 1 (Lamr1). This locus contained an intron-processed retroposon that was
      transcribed in the mice with RVD. Introduction of a mutated Lamr1 gene into
      normal mice by breeding or by direct injection caused susceptibility to RVD,
      which was similar to that seen in the RVD mice. An in vitro study of
      cardiomyocytes expressing the product of mutated Lamr1 showed early cell death
      accompanied by alteration of the chromatin architecture. We found that
      heterochromatin protein 1 (HP1) bound specifically to mutant LAMR1. HP1 is a
      dynamic regulator of heterochromatin sites, suggesting that mutant LAMR1 impairs
      a crucial process of transcriptional regulation. Indeed, mutant LAMR1 caused
      specific changes to gene expression in cardiomyocytes, as detected by gene chip
      analysis. Thus, we concluded that products of the Lamr1 retroposon interact with
      HP1 to cause degeneration of cardiomyocytes. This mechanism may also contribute
      to the etiology of human ARVD.

PMID- 14730305
TI  - Neural systems supporting interoceptive awareness.
AB  - Influential theories of human emotion argue that subjective feeling states
      involve representation of bodily responses elicited by emotional events. Within
      this framework, individual differences in intensity of emotional experience
      reflect variation in sensitivity to internal bodily responses. We measured
      regional brain activity by functional magnetic resonance imaging (fMRI) during an
      interoceptive task wherein subjects judged the timing of their own heartbeats. We
      observed enhanced activity in insula, somatomotor and cingulate cortices. In
      right anterior insular/opercular cortex, neural activity predicted subjects'
      accuracy in the heartbeat detection task. Furthermore, local gray matter volume
      in the same region correlated with both interoceptive accuracy and subjective
      ratings of visceral awareness. Indices of negative emotional experience
      correlated with interoceptive accuracy across subjects. These findings indicate
      that right anterior insula supports a representation of visceral responses
      accessible to awareness, providing a substrate for subjective feeling states.

PMID- 14730306
TI  - First spikes in ensembles of human tactile afferents code complex spatial
      fingertip events.
AB  - It is generally assumed that primary sensory neurons transmit information by
      their firing rates. However, during natural object manipulations, tactile
      information from the fingertips is used faster than can be readily explained by
      rate codes. Here we show that the relative timing of the first impulses elicited
      in individual units of ensembles of afferents reliably conveys information about
      the direction of fingertip force and the shape of the surface contacting the
      fingertip. The sequence in which different afferents initially discharge in
      response to mechanical fingertip events provides information about these events
      faster than the fastest possible rate code and fast enough to account for the use
      of tactile signals in natural manipulation.

PMID- 14730307
TI  - LTP is accompanied by an enhanced local excitability of pyramidal neuron
      dendrites.
AB  - The propagation and integration of signals in the dendrites of pyramidal neurons
      is regulated, in part, by the distribution and biophysical properties of voltage
      gated ion channels. It is thus possible that any modification of these channels
      in a specific part of the dendritic tree might locally alter these signaling
      processes. Using dendritic and somatic whole-cell recordings, combined with
      calcium imaging in rat hippocampal slices, we found that the induction of long
      term potentiation (LTP) was accompanied by a local increase in dendritic
      excitability that was dependent on the activation of NMDA receptors. These
      changes favored the back-propagation of action potentials into this dendritic
      region with a subsequent boost in the Ca(2+) influx. Dendritic cell-attached
      patch recordings revealed a hyperpolarized shift in the inactivation curve of
      transient, A-type K(+) currents that can account for the enhanced excitability.
      These results suggest an important mechanism associated with LTP for shaping
      signal processing and controlling dendritic function.

PMID- 14730308
TI  - Cypin regulates dendrite patterning in hippocampal neurons by promoting
      microtubule assembly.
AB  - Dendrite branching has an important role in normal brain function. Here we report
      that overexpression of cypin, a protein that has guanine deaminase activity and
      is expressed in developing processes in rat hippocampal neurons, results in
      increased dendrite branching in primary culture. Mutant cypin proteins that lack
      guanine deaminase activity act in a dominant-negative manner when expressed in
      primary neurons. Furthermore, we knocked down cypin protein levels using a new
      strategy: expressing a 5' end-mutated U1 small nuclear RNA (snRNA) to inhibit
      maturation of cypin mRNA. Neurons that express this mutant snRNA show little or
      no detectable cypin protein and fewer dendrites than normal. In addition, we
      found that cypin binds directly to tubulin heterodimers and promotes microtubule
      polymerization. Thus, our results demonstrate a new pathway by which dendrite
      patterning is regulated, and we also introduce a new method for decreasing
      endogenous protein expression in neurons.

PMID- 14730309
TI  - Agonist-independent modulation of N-type calcium channels by ORL1 receptors.
AB  - We have investigated modulation of voltage-gated calcium channels by nociceptin
      (ORL1) receptors. In rat DRG neurons and in tsA-201 cells, nociceptin mediated a
      pronounced inhibition of N-type calcium channels, whereas other calcium channel
      subtypes were unaffected. In tsA-201 cells, expression of N-type channels with
      human ORL1 resulted in a voltage-dependent G-protein inhibition of the channel
      that occurred in the absence of nociceptin, the ORL1 receptor agonist. Consistent
      with this observation, native N-type channels of small nociceptive dorsal root
      ganglion (DRG) neurons also had tonic inhibition by G proteins. Biochemical
      characterization showed the existence of an N-type calcium channel-ORL1 receptor
      signaling complex, which efficiently exposes N-type channels to constitutive ORL1
      receptor activity. Calcium channel activity is thus regulated by changes in ORL1
      receptor expression, which provides a possible molecular mechanism for the
      development of tolerance to opioid receptor agonists.

PMID- 14730310
TI  - Opiate state controls bi-directional reward signaling via GABAA receptors in the
      ventral tegmental area.
AB  - The neural mechanisms that mediate the transition from a drug-naive state to a
      state of drug dependence and addiction are not yet known. Here we show that a
      discrete population of GABA(A) receptors in the mammalian ventral tegmental area
      (VTA) serves as a potential addiction switching mechanism by gating reward
      transmission through one of two neural motivational systems: either a dopamine
      independent (opiate-naive) or a dopaminergic (opiate-dependent or opiate
      withdrawn) system. Bi-directional transmission of reward signals through this
      GABA(A) receptor substrate is dynamically controlled by the opiate state of the
      organism and involves a molecular alteration of the GABA(A) receptor. After
      opiate exposure and subsequent withdrawal, the functional conductance properties
      of the rat VTA GABA(A) receptor switch from an inhibitory to an excitatory
      signaling mode.

PMID- 14730311
TI  - Perceptual learning improves efficiency by re-tuning the decision 'template' for
      position discrimination.
AB  - Visual position discrimination improves with practice; however, the mechanism(s)
      underlying this improvement are not yet known. We used positional noise to
      explore the underlying neural mechanisms and found that position discrimination
      improved with practice over a range of noise levels. This improvement can be
      largely explained by an increasing efficiency with which observers used
      positional information in the stimulus. In a second experiment, we tested the
      hypothesis that the improved efficiency reflects a re-tuning of the observers'
      perceptual 'template'--the weightings of inputs from basic visual mechanisms--to
      more closely match the ideal template required to perform the perceptual task.
      Using a new technique to measure which parts of the stimulus influenced the
      observer's performance, we were able to record the re-tuning of the decision
      template across training sessions; we found a robust and steady increase in
      template efficiency during learning.

PMID- 14730313
TI  - Modulation of heat shock gene expression by the TAC1 chromatin-modifying complex.
AB  - Rapid induction of the Drosophila melanogaster heat shock gene hsp70 is achieved
      through the binding of heat shock factor (HSF) to heat shock elements (HSEs)
      located upstream of the transcription start site (reviewed in ref. 3). The
      subsequent recruitment of several other factors, including Spt5, Spt6 and FACT,
      is believed to facilitate Pol II elongation through nucleosomes downstream of the
      start site. Here, we report a novel mechanism of heat shock gene regulation that
      involves modifications of nucleosomes by the TAC1 histone modification complex.
      After heat stress, TAC1 is recruited to several heat shock gene loci, where its
      components are required for high levels of gene expression. Recruitment of TAC1
      to the 5'-coding region of hsp70 seems to involve the elongating Pol II complex.
      TAC1 has both histone H3 Lys 4-specific (H3-K4) methyltransferase (HMTase)
      activity and histone acetyltransferase activity through Trithorax (Trx) and CREB
      binding protein (CBP), respectively. Consistently, TAC1 is required for
      methylation and acetylation of nucleosomal histones in the 5'-coding region of
      hsp70 after induction, suggesting an unexpected role for TAC1 during
      transcriptional elongation.

PMID- 14730312
TI  - ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.
AB  - The apoptosis-associated speck-like protein (ASC) is an unusual adaptor protein
      that contains the Pyrin/PAAD death domain in addition to the CARD protein-protein
      interaction domain. Here, we present evidence that ASC can function as an adaptor
      molecule for Bax and regulate a p53-Bax mitochondrial pathway of apoptosis. When
      ectopically expressed, ASC interacted directly with Bax, colocalized with Bax to
      the mitochondria, induced cytochrome c release with a significant reduction of
      mitochondrial membrane potential and resulted in the activation of caspase-9, -2
      and -3. The rapid induction of apoptosis by ASC was not observed in Bax-deficient
      cells. We also show that induction of ASC after exposure to genotoxic stress is
      dependent on p53. Blocking of endogenous ASC expression by small-interfering RNA
      (siRNA) reduced the apoptotic response and inhibited translocation of Bax to
      mitochondria in response to p53 or genotoxic insult, suggesting that ASC is
      required to translocate Bax to the mitochondria. Our findings demonstrate that
      ASC has an essential role in the intrinsic mitochondrial pathway of apoptosis
      through a p53-Bax network.

PMID- 14730314
TI  - A novel mechanism for the store-operated calcium influx pathway.
AB  - Activation of store-operated channels (SOCs) and capacitative calcium influx are
      triggered by depletion of intracellular calcium stores. However, the exact
      molecular mechanism of such communication remains unclear. Recently, we
      demonstrated that native SOC channels can be activated by calcium influx factor
      (CIF) that is produced upon depletion of calcium stores, and showed that Ca(2+)
      independent phospholipase A(2) (iPLA(2)) has an important role in the store
      operated calcium influx pathway. Here, we identify the key plasma-membrane
      delimited events that result in activation of SOC channels. We also propose a
      novel molecular mechanism in which CIF displaces inhibitory calmodulin (CaM) from
      iPLA(2), resulting in activation of iPLA(2) and generation of lysophospholipids
      that in turn activate soc channels and capacitative calcium influx. Upon
      refilling of the stores and termination of CIF production, CaM rebinds to
      iPLA(2), inhibits it, and the activity of SOC channels and capacitative calcium
      influx is terminated.

PMID- 14730315
TI  - Intensity-based protein identification by machine learning from a library of
      tandem mass spectra.
AB  - Tandem mass spectrometry (MS/MS) has emerged as a cornerstone of proteomics owing
      in part to robust spectral interpretation algorithms. Widely used algorithms do
      not fully exploit the intensity patterns present in mass spectra. Here, we
      demonstrate that intensity pattern modeling improves peptide and protein
      identification from MS/MS spectra. We modeled fragment ion intensities using a
      machine-learning approach that estimates the likelihood of observed intensities
      given peptide and fragment attributes. From 1,000,000 spectra, we chose 27,000
      with high-quality, nonredundant matches as training data. Using the same 27,000
      spectra, intensity was similarly modeled with mismatched peptides. We used these
      two probabilistic models to compute the relative likelihood of an observed
      spectrum given that a candidate peptide is matched or mismatched. We used a
      'decoy' proteome approach to estimate incorrect match frequency, and demonstrated
      that an intensity-based method reduces peptide identification error by 50-96%
      without any loss in sensitivity.

PMID- 14730316
TI  - Generation of marker-free plastid transformants using a transiently cointegrated
      selection gene.
AB  - Genetic engineering of higher plant plastids typically involves stable
      introduction of antibiotic resistance genes as selection markers. Even though
      chloroplast genes are maternally inherited in most crops, the possibility of
      marker transfer to wild relatives or microorganisms cannot be completely
      excluded. Furthermore, marker expression can be a substantial metabolic drain.
      Therefore, efficient methods for complete marker removal from plastid
      transformants are necessary. One method to remove the selection gene from higher
      plant plastids is based on loop-out recombination, a process difficult to control
      because selection of homoplastomic transformants is unpredictable. Another method
      uses the CRE/lox system, but requires additional retransformation and sexual
      crossing for introduction and subsequent removal of the CRE recombinase. Here we
      describe the generation of marker-free chloroplast transformants in tobacco using
      the reconstitution of wild-type pigmentation in combination with plastid
      transformation vectors, which prevent stable integration of the kanamycin
      selection marker. One benefit of a procedure using mutants is that marker-free
      plastid transformants can be produced directly in the first generation (T0)
      without retransformation or crossing.

PMID- 14730317
TI  - Assessing the survival of transgenic plant DNA in the human gastrointestinal
      tract.
AB  - The inclusion of genetically modified (GM) plants in the human diet has raised
      concerns about the possible transfer of transgenes from GM plants to intestinal
      microflora and enterocytes. The persistence in the human gut of DNA from dietary
      GM plants is unknown. Here we study the survival of the transgene epsps from GM
      soya in the small intestine of human ileostomists (i.e., individuals in which the
      terminal ileum is resected and digesta are diverted from the body via a stoma to
      a colostomy bag). The amount of transgene that survived passage through the small
      bowel varied among individuals, with a maximum of 3.7% recovered at the stoma of
      one individual. The transgene did not survive passage through the intact
      gastrointestinal tract of human subjects fed GM soya. Three of seven ileostomists
      showed evidence of low-frequency gene transfer from GM soya to the microflora of
      the small bowel before their involvement in these experiments. As this low level
      of epsps in the intestinal microflora did not increase after consumption of the
      meal containing GM soya, we conclude that gene transfer did not occur during the
      feeding experiment.

PMID- 14730318
TI  - FRET between cardiac Na+ channel subunits measured with a confocal microscope and
      a streak camera.
AB  - When and where proteins associate is a central question in many biomolecular
      studies. Forster resonance energy transfer (FRET) measurements can be used to
      address this question when the interacting proteins are labeled with appropriate
      donor and acceptor fluorophores. We describe an improved method to determine FRET
      efficiency that uses a mode-locked laser, a confocal microscope and a streak
      camera. We applied this method to study the association of alpha and beta(1)
      subunits of the human cardiac sodium channel. The subunits were tagged with the
      cyan and yellow variants of the green fluorescent protein (GFP) and expressed in
      human embryonic kidney (HEK293) cells. Pronounced FRET between the channel
      subunits in the endoplasmic reticulum (ER) suggested that the subunits associate
      before they reach the plasma membrane. The described method allows simultaneous
      measurement of donor and acceptor fluorescence decays and provides an
      intrinsically validated estimate of FRET efficiency.

PMID- 14730319
TI  - The conserved kinetochore protein shugoshin protects centromeric cohesion during
      meiosis.
AB  - Meiosis comprises a pair of specialized nuclear divisions that produce haploid
      germ cells. To accomplish this, sister chromatids must segregate together during
      the first meiotic division (meiosis I), which requires that sister chromatid
      cohesion persists at centromeres. The factors that protect centromeric cohesion
      during meiosis I have remained elusive. Here we identify Sgo1 (shugoshin), a
      protector of the centromeric cohesin Rec8 in fission yeast. We also identify a
      homologue of Sgo1 in budding yeast. We provide evidence that shugoshin is widely
      conserved among eukaryotes. Moreover, we identify Sgo2, a paralogue of shugoshin
      in fission yeast, which is required for faithful mitotic chromosome segregation.
      Localization of Sgo1 and Sgo2 at centromeres requires the kinase Bub1,
      identifying shugoshin as a crucial target for the kinetochore function of Bub1.
      These findings provide insights into the evolution of meiosis and kinetochore
      regulation during mitosis and meiosis.

PMID- 14730320
TI  - Trends in hypertension epidemiology in India.
AB  - Cardiovascular diseases caused 2.3 million deaths in India in the year 1990; this
      is projected to double by the year 2020. Hypertension is directly responsible for
      57% of all stroke deaths and 24% of all coronary heart disease deaths in India.
      Indian urban population studies in the mid-1950s used older WHO guidelines for
      diagnosis (BP > or =160 and/or 95 mmHg) and reported hypertension prevalence of
      1.2-4.0%. Subsequent studies report steadily increasing prevalence from 5% in
      1960s to 12-15% in 1990s. Hypertension prevalence is lower in the rural Indian
      population, although there has been a steady increase over time here as well.
      Recent studies using revised criteria (BP > or =140 and/or 90 mmHg) have shown a
      high prevalence of hypertension among urban adults: men 30%, women 33% in Jaipur
      (1995), men 44%, women 45% in Mumbai (1999), men 31%, women 36% in
      Thiruvananthapuram (2000), 14% in Chennai (2001), and men 36%, women 37% in
      Jaipur (2002). Among the rural populations, hypertension prevalence is men 24%,
      women 17% in Rajasthan (1994). Hypertension diagnosed by multiple examinations
      has been reported in 27% male and 28% female executives in Mumbai (2000) and 4.5%
      rural subjects in Haryana (1999). There is a strong correlation between changing
      lifestyle factors and increase in hypertension in India. The nature of genetic
      contribution and gene-environment interaction in accelerating the hypertension
      epidemic in India needs more studies. Pooling of epidemiological studies shows
      that hypertension is present in 25% urban and 10% rural subjects in India. At an
      underestimate, there are 31.5 million hypertensives in rural and 34 million in
      urban populations. A total of 70% of these would be Stage I hypertension
      (systolic BP 140-159 and/or diastolic BP 90-99 mmHg). Recent reports show that
      borderline hypertension (systolic BP 130-139 and/or diastolic BP 85-89 mmHg) and
      Stage I hypertension carry a significant cardiovascular risk and there is a need
      to reduce this blood pressure. Population-based cost-effective hypertension
      control strategies should be developed.

PMID- 14730321
TI  - Validation of the Finometer device for measurement of blood pressure in black
      women.
AB  - The improved Finapres apparatus, known as the Finometer, measures finger blood
      pressure noninvasively on a beat-to-beat basis and gives waveform measurements
      similar to intra-arterial recordings. The Finometer measures brachial pressure
      and corrects for finger pressure accordingly. It also corrects for the
      hydrostatic height of the finger with respect to the heart level. The objective
      was to validate the Finometer according to the revised British Hypertension
      Society (BHS) protocol and the criteria of the Association for the Advancement of
      Medical Instrumentation (AAMI). We carried out a main validation test using a
      subject group of 102 black women, which was also divided into smaller groups,
      namely 24 hypertensives, 25 obese normotensive and 35 lean normotensive women.
      Finometer and mercury sphygmomanometer blood pressure (BP) measurements were
      taken early in the morning before breakfast, after the subjects stayed overnight
      in a research unit. Within the whole subject group, the Finometer satisfied the
      AAMI criteria for accuracy and achieved an overall A/B grading according to the
      BHS criteria. The sphygmomanometer measurements were 128+/-20/78+/-12 mmHg
      compared to 130+/-20/78+/-11 mmHg for the Finometer. The average differences
      between the mercury sphygmomanometer and Finometer readings for systolic and
      diastolic BP were, respectively, -1.83+/-6.8 and 0.88+/-7.5. Systolic readings of
      the Finometer device differed by less than 5 mmHg for 64%, by less than 10 mmHg
      for 86% and differed by less than 15 mmHg for 96% of all readings. A total of 63%
      of all diastolic readings of the Finometer by less than 5 mmHg, 85% by less than
      10 mmHg and 94% of all readings differed by less than 15 mmHg. On the basis of
      these results, the Finometer device satisfied the validation criteria of AAMI and
      received an A/B grading according to the BHS protocol. It can therefore be
      recommended for measurements in the clinical set-up and for research purposes.

PMID- 14730322
TI  - Diagnostic value of strategy for the detection of white coat hypertension based
      on ambulatory and home blood pressure monitoring.
AB  - An algorithm has been proposed for the detection of white coat hypertension among
      subjects with elevated blood pressure (BP) on at least three clinic visits using
      home BP monitoring (screening test) and, if this is low, ambulatory BP monitoring
      (diagnostic test). This study aims to test this strategy in practice. The
      proposed algorithm was applied in 133 untreated subjects with elevated BP
      assessed in a previous prospective study using repeated clinic, home and
      ambulatory BP measurements. The proportions of detected and missed cases of white
      coat hypertension and the diagnostic value of the algorithm were calculated. By
      applying the algorithm, 99 subjects (74%) were found eligible for home
      measurements and 35 (26%) for ambulatory monitoring. There were 38 subjects with
      white coat hypertension (38%), of whom 15 (39%) were not detected by the proposed
      strategy. The sensitivity, specificity, and the positive and negative predictive
      value of the algorithm to diagnose white coat hypertension were 61, 81, 66 and
      77%, respectively. Of the 34 subjects with normal BP on the third clinic visit,
      15 (42%) had elevated home and/or ambulatory BP. These data suggest that, using
      the proposed strategy, many white coat hypertensives may remain undetected and
      may receive unnecessary long-term drug treatment. Therefore, more research is
      needed on the optimal strategy for detecting white coat hypertension in clinical
      practice.

PMID- 14730323
TI  - Which patients with hypertension and atherosclerotic renal artery stenosis
      benefit from immediate intervention?
AB  - The objective was to identify subgroups of patients with hypertension and
      atherosclerotic renal artery stenosis who may benefit from immediate
      intervention. In the DRASTIC study, patients with hypertension, significant
      atherosclerotic renal artery stenosis, and a normal or mildly impaired renal
      function were randomized between immediate balloon angioplasty (PTRA; n=56) and
      drug therapy followed by angioplasty after 3 months, if needed (Med-PTRA; n=50).
      In this secondary analysis of the data, changes in the renal function and blood
      pressure after 1 year were studied by analysis of covariance in the following
      subgroups: patients with positive captopril-renin challenge test, abnormal
      captopril renogram, recently developed hypertension, bilateral stenosis, and
      severe stenosis. We found a benefit of immediate angioplasty only for patients
      with bilateral stenosis. Their creatinine clearance had decreased (mean+/-s.d.: 
      4.2+/-13.5 ml/min) in the Med-PTRA group, whereas it had improved substantially
      (+10.0+/-15.7 ml/min) in the PTRA group (P=0.02). For patients with unilateral
      stenosis, the change in creatinine clearance did not differ between PTRA and Med
      PTRA (+4.3+/-15.5 and +1.3+/-12.5 ml/min, respectively). The patients with
      bilateral stenosis also seemed to benefit most from immediate intervention with
      regard to blood pressure control. None of the other subgroups had a clear benefit
      of immediate intervention regarding renal function or blood pressure control. In
      conclusion, intervention should not be postponed in patients with bilateral
      stenosis, even if renal function is normal. Other hypertensive patients with
      atherosclerotic renal artery disease could initially well be treated by
      aggressive multidrug therapy alone unless hypertension persists or renal function
      deteriorates.

PMID- 14730324
TI  - Impact of the high-risk and mass strategies on hypertension control and stroke
      mortality in primary health care.
AB  - Stroke has been the second leading cause of death in Taiwan in recent years.
      Following a 6-month pilot study in Yu-Chi in 1993, a 3.5-year hypertension
      control programme was performed to examine the effectiveness of combined high
      risk and mass strategies in a rural community with limited medical resources. All
      Yu-Chi residents aged 40 years and older were invited to participate in the
      programme. The high-risk strategies included hypertension screening, home visits,
      and follow-up for the hypertensives. The mass strategies included health
      education and village-based campaigns. Changes over time in the participants'
      hypertension knowledge, behaviour, and blood pressure control status were
      evaluated. A comparison of the stroke mortality between the intervention
      community and a neighbourhood reference community before and after the
      intervention programme was performed. A total of 4977 residents were screened and
      3761 completed the first and second rescreening. The hypertension knowledge and
      behaviour scores in the hypertensives significantly improved, systolic and
      diastolic blood pressure and waist-to-hip ratio significantly reduced, and the
      rates of hypertension treatment and control increased significantly at 1 and 3.5
      years after intervention. In contrast, blood pressure levels increased
      significantly in the normotensives. Between 1994 and 1997, stroke mortality rate
      decreased by 39.9 and 4.8% in the intervention and reference communities,
      respectively. The results indicated that the community-based hypertension control
      programme was effective. The immediate decline in stroke mortality appeared to be
      mostly related to the high-risk strategies.

PMID- 14730325
TI  - Diurnal blood pressure variation in pheochromocytoma, primary aldosteronism and
      Cushing's syndrome.
AB  - We examined circadian blood pressure (BP) variation (expressed as a relative
      night-time BP decline) in subjects with primary aldosteronism (78 patients),
      pheochromocytoma (n=45) and Cushing's syndrome (n=18). Subjects with aldosterone
      producing adenoma (n=21) and pheochromocytoma (n=27) were also investigated after
      the tumour removal. In all, 65 patients with essential hypertension served as a
      control group. The night-time BP decline was significantly attenuated in all
      three forms of endocrine hypertension compared to the control group (primary
      aldosteronism P<0.0001, pheochromocytoma P<0.0001 for systolic and diastolic BP
      and Cushing's syndrome P<0.0001/<0.001 vs essential hypertension). In the case of
      pheochromocytoma, the absence of the night-time BP decrease was more prominent
      compared to the primary aldosteronism group (P=0.003/0.001) and for the diastolic
      BP also in comparison with the Cushing's syndrome group (P=0.03). Tumour removal
      led in both groups to the restoration of the previously altered circadian rhythm
      (aldosterone-producing adenoma: P=0.0005/0.0009; pheochromocytoma:
      P=0.001/0.0007). Our study demonstrates a blunted circadian BP variation in all
      forms of adrenal hypertension in comparison with essential hypertension. This
      reduction of the night-time BP decrease was more prominent in pheochromocytoma
      than in primary aldosteronism or Cushing's syndrome.

PMID- 14730326
TI  - Secular decrease in blood pressure and reduction in mortality from cardiovascular
      disease in Israeli workers.
AB  - The reasons for the dramatic reduction in age-adjusted mortality from
      cardiovascular disease (CVD) since the 1970s in developed countries remain
      uncertain. In the following study we compare the cardiovascular and all-cause
      mortality rates over an 11-year period in two well-defined employed male cohorts
      aged 40-69 years old recruited 24 years apart. Blood pressure and other risk
      markers for CVD were assessed at the time of inception (1963 for 10 048 male
      civil servants and 1985-1987 for 2237 male industrial workers). Compared to the
      1987 cohort, the 1963 cohort show an increase of 8.7 mmHg in the mean systolic
      blood pressure (SBP) (95% confidence interval (CI): 7.7, 9.6) and a concomitant
      hazard ratio for CVD mortality of 1.47 (95% CI: 1.16, 1.87). After adding SBP to
      the analysis, the hazard ratio for CVD mortality in the 1963 cohort decreased to
      1.18 (95% CI: 0.88, 1.43). Adding the other risk modifiers to the analysis did
      not modify the hazard ratio to the same extent. Similar results were obtained for
      all-cause mortality. We conclude that declining blood pressure values are a major
      factor in explaining the secular decrease in CVD mortality over a period of 24
      years in Israel.

PMID- 14730327
TI  - Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene
      polymorphism in humans.
AB  - Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates
      angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D)
      angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE
      levels by 40%. In rats, a similar polymorphism determines ACE levels which are
      inversely associated to NEP activity. The objective of this study is to evaluate
      the relationship between ACE expression and plasma NEP activity in normotensive
      subjects and in hypertensive patients. In total, 58 consecutive patients with
      hypertension, evaluated in our Hypertension Clinic, were compared according to
      their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE
      activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both
      DD ACE groups (normotensives and hypertensives) compared with their respective ID
      and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of
      the hypertensive status on ACE activity was observed (P<0.001). In normotensive
      DD ACE subjects, NEP activity was 0.30+/-0.02 U/ml, whereas in the normotensive
      II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and
      48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity
      was 0.47+/-0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04)
      and an interaction effect between the I/D ACE genotype and the hypertensive
      status were also observed (P<0.001). These results are consistent with a normal
      and inverse relationship between the ACE polymorphism and NEP activity in
      normotensive humans (as is also observed in rats). This normal relationship is
      not observed in hypertensive patients.

PMID- 14730328
TI  - Intensive training of patients with hypertension is effective in modifying
      lifestyle risk factors.
AB  - The burden of insufficiently treated arterial hypertension is still
      underestimated. In addition to pharmacological therapy, patient training is a
      valuable therapeutic option. During 1998-1999, the Institute for Preventive
      Medicine conducted an intensive training programme in cooperation with regional
      practitioners. The goal of this programme was to educate patients about their
      disease and motivate them to comply with the therapy. To evaluate the effectivity
      of this programme, 126 patients with arterial hypertension were trained. They
      received eight training sessions of 90 min each. In 90 patients blood pressure
      measurements before and 6 months after training were available. In addition, data
      concerning health status and lifestyle risk factors were analysed with
      standardised questionnaires. There was a marked reduction in blood pressure after
      6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean
      body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by
      0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more
      marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline
      of blood pressure was also greater in obese patients, but did not reach
      statistical significance. The activity score for physical exercise increased
      overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about
      hypertension increased as well (P<0.01). Of all the quality life measurements,
      the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the
      patients' self-estimation. In conclusion, training of hypertensive patients has a
      profound effect on blood pressure control. It motivates patients to change
      lifestyle risk factors, namely to lose weight, and increases the patients'
      physical activity level, thereby decreasing the patients' blood pressure. Thus,
      intensive training programmes are effective and should be used on a widespread
      basis.

PMID- 14730329
TI  - Hypertensive encephalopathy with predominant brain stem involvement: MRI
      findings.

PMID- 14730330
TI  - Analysis of blood pressure waveform: a new method for the classification of
      hypertensive pregnancy disorders.

PMID- 14730331
TI  - Potentiation of oncolytic adenoviral vector efficacy with gutless vectors
      encoding GMCSF or TRAIL.
AB  - Oncolytic adenoviral vectors selectively replicate in and lyse human tumor cells,
      providing a promising means for targeted tumor destruction. However, oncolytic
      vectors have limited capacity for incorporation of additional genetic material
      that could encode therapeutic transgenes and/or transcriptional regulatory
      control elements to augment the efficacy and/or safety of the vector. Therefore,
      we hypothesized that coadministration of an oncolytic vector with a replication
      defective, gutless adenoviral vector encoding a therapeutic transgene would
      result in replication of both vectors within a tumor and potentiate antitumor
      efficacy relative to the use of either vector alone. We constructed gutless
      vectors encoding the murine granulocyte-macrophage colony-stimulating factor
      (AGVmGMF) or human tumor necrosis factor alpha-related apoptosis-inducing ligand
      (AGVhTRAIL) gene and tested the ability of these vectors to augment the efficacy
      of an oncolytic vector (Ar6pAE2fE3F) in a potentiating vector strategy. In Hep3B
      cells in vitro, cotreatment with Ar6pAE2fE3F increased transgene expression from
      AGVhTRAIL and permitted replication of AGVhTRAIL, suggesting that an oncolytic
      vector can propagate gutless vector spread in vivo. In pre-established Hep3B
      xenograft tumors, neither gutless vector alone inhibited tumor growth; however,
      coadministration of AGVmGMF or AGVhTRAIL with Ar6pAE2fE3F significantly reduced
      tumor growth relative to Ar6pAE2fE3F alone. Additionally, use of AGVhTRAIL with
      Ar6pAE2fE3F increased the number of complete or partial tumor regressions
      observed at study end. These data provide evidence that coadministration of an
      oncolytic vector with a gutless vector holds promise for potentiating tumor
      ablation efficacy.

PMID- 14730332
TI  - Imaging of metastatic pulmonary tumors following NIS gene transfer using single
      photon emission computed tomography.
AB  - The Na+/I- symporter (NIS) is a membrane glycoprotein that facilitates the uptake
      of iodine into thyroid follicular cells. Recently, we and others have
      demonstrated the feasibility of imaging subcutaneous xenografts expressing
      exogenous NIS, suggesting that NIS may serve as an imaging reporter gene to
      monitor vector delivery and therapeutic gene expression. In this study, we
      established NIS-expressing pulmonary tumors in nude mice to investigate the
      minimal tumor size required for in vivo detection of pulmonary tumors by single
      photon emission computed tomography (SPECT) with pinhole collimation. In order to
      define the anatomic location of NIS-expressing tumor nodules detectable by SPECT,
      we performed simultaneous, dual-isotope imaging. We injected 1 mCi 99mTc-MAA via
      tail vein to image pulmonary perfusion and injected 1 mCi Na125I
      intraperitoneally to image NIS-expressing tumors. Fused images showed that 99mTc
      MAA perfusion defects correlated with NIS-mediated 125I uptake. Post-mortem
      analysis revealed that tumors 3 mm in diameter could be detected by SPECT with
      pinhole collimation. These studies demonstrate the feasibility of SPECT to detect
      pulmonary tumors expressing exogenous NIS in mice.

PMID- 14730333
TI  - Elderly age and prior autologous transplantation have a deleterious effect on
      survival following allogeneic peripheral blood stem cell transplantation with
      reduced-intensity conditioning: results from the Spanish multicenter prospective
      trial.
AB  - Over a 3-year period, 145 patients ineligible for myeloablative conditioning
      underwent reduced-intensity conditioning (RIC) hematopoietic stem cell
      transplantation (SCT) from an HLA-identical sibling in a prospective study. The
      median age was 54 years, 88 patients were male and 61 patients were beyond the
      early-intermediate phase of their disease. The 100-day probability of developing
      grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year
      probability of developing chronic extensive GVHD was 41%. The 1-year
      probabilities of transplant-related mortality (TRM), overall (OS) and progression
      free survival were 20, 60 and 52%, respectively. Multivariate analyses found a
      better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a
      higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and
      (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and
      >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively
      (P<0.001). In summary, our study shows that elderly patients have a higher TRM
      following an RIC protocol. However, age by itself should not preclude these RIC
      transplants, since TRM appears to be unacceptably high only in the presence of
      additional adverse factors.

PMID- 14730334
TI  - Visceral leishmaniasis: a new opportunistic infection in hematopoietic stem-cell
      transplanted patients.

PMID- 14730335
TI  - Long-term follow-up of patients with poor prognosis germ cell tumor treated with
      early high-dose chemotherapy with hematopoietic progenitor cell support: a single
      center experience.
AB  - The 5-year overall survival rate of patients with germ cell tumor (GCT) with poor
      prognosis, according to the International Germ Cell Cancer Collaborative Group
      (IGCCCG) classification, is 48% after standard-dose chemotherapy and surgery, if
      necessary. Two recent studies have showed that early high-dose chemotherapy
      (HDCT) with hematopoietic progenitor cell support (HPCS) may induce a 2-year
      overall survival rate of 78% in these patients. We report the long-term results
      of the experience at the Department of Oncology in Ravenna with early HDCT and
      HPCS in GCT patients with poor prognosis (IGCCCG criteria). Between 1987 and
      2002, 18 poor prognosis GCT patients (17 M, one F), median age 24.5 years (range,
      17-52), were treated with early HDCT with HPCS. In total, (67%) patients achieved
      a complete remission and they are continuously disease-free at a median follow-up
      of 9.2 years (range, 1.7-16.2). One treatment-related death occurred. No patient
      developed myelodysplasia or a secondary leukemia. This is notably the longest
      follow-up reported in patients having received HDCT in this setting. No patient
      achieving a complete remission relapsed. The role of HDCT in poor prognosis GCT
      will be defined from the ongoing phase III randomized trials.

PMID- 14730336
TI  - Outcomes of autologous stem cell transplantation in patients with multiple
      myeloma who received dexamethasone-based nonmyelosuppressive induction therapy.
AB  - High-dose chemotherapy (HDC) followed by autologous stem cell transplantation
      (ASCT) improves survival in myeloma (MM). The role of induction therapy on
      outcomes of ASCT in MM has not been systematically studied. Nonmyelosuppressive
      (NMS) steroid-based induction can be used in MM, with the potential of reducing
      neutropenias and other toxic effects prior to ASCT. NMS induction however could
      be associated with poorer outcomes if disease control or stem cell collection
      were inadequate. We studied outcomes of 136 MM patients who underwent HDC and
      ASCT as part of their initial therapy between March 1998 and December 2000. Of
      these, 46 received HDC and ASCT without any exposure to myelosuppressive agents,
      39 received myelosuppressive therapy for disease control and/or stem cell
      collection, and 51 received alkylating agent-based initial treatment. We compared
      OS and EFS rates, stem cell collectability, and contamination of the grafts with
      monoclonal plasma cells. After a median of 33 months, response rates, EFS and OS
      rates were comparable in the three groups of patients. Adequacy of stem cell
      collection and plasma cell contamination were similar. Our data support the
      hypothesis that NMS induction for patients with MM is safe and effective and does
      not compromise the results of HDC.

PMID- 14730337
TI  - A pilot study of reduced intensity conditioning and allogeneic stem cell
      transplantation from unrelated cord blood and matched family donors in children
      and adolescent recipients.
AB  - Reduced intensity (RI) allogeneic stem cell transplantation (AlloSCT) was
      initially demonstrated in adults following HLA-matched family and unrelated adult
      donor AlloSCT. There is little information about RI AlloSCT in children. We
      report results of a pilot study of RI AlloSCT in 21 recipients (< or =21 years).
      Age: median 13 (0.5-21) years, 8F:13M, 14 unrelated cord blood units (UCB) (10
      4/6, 4 5/6), two related BM (6/6, 5/6), four related PBSC (2 6/6, 2 5/6), and one
      related BM+PBSC (6/6). RI: fludarabine, busulfan (n=14); fludarabine,
      cyclophosphamide (n=4); fludarabine, melphalan (n=1); total body irradiation,
      fludarabine, cyclophosphamide (n=1); or fludarabine, cyclophosphamide, and
      etoposide (n=1). Graft-versus-host disease prophylaxis: FK506 0.03 mg/kg/day and
      mycophenolate mofetil 15 mg/kg/q 12 h. UCB median nuc/kg and CD34/kg was 4.3 x
      10(7)/kg (0.9-10.8) and 1.9 x 10(5)/kg (0.3-6.9), and related BM/PBSC median
      nuc/kg and CD34/kg was 8.3 x 10(8) (4.7-18.9) and 5.0 x 10(6)/kg (4.6-6.4).
      Maximal chimerism following unrelated cord blood transplantation, 100% x 7, 98% x
      1, 95% x 2, 55% x 1, and 0% x 3; related PBSC/BM, 100% x 5, 65% x 1, and 55% x 1.
      Graft failure occurred in 5/21 (24%). In summary, RI AlloSCT in children is
      feasible and tolerable (< or =25% GF) and results in > or =85% of recipients
      initially achieving > or =50% donor chimerism.

PMID- 14730338
TI  - Effect of cumulative etoposide doses on the outcome of autologous peripheral
      blood progenitor-cell transplantation for lymphoma.
AB  - Studies evaluating the effects of previous chemotherapy on stem-cell yield and
      hematological recovery after autologous peripheral-blood progenitor-cell
      transplantation (PBPCT) have shown conflicting results. We have retrospectively
      analyzed 103 consecutive lymphoma patients treated with the BEAM regimen and
      autologous PBPCT. The impact of the different chemotherapeutic drugs (cumulative
      doses) on stem-cell yield and transplant-related toxicity was investigated.
      Highly significant differences in platelet recovery (>20 x 10(9)/l) were observed
      between patients receiving less or more than 750 mg/m(2) of etoposide before
      transplant (15 vs 29 days, P=0.001), and between patients receiving less or more
      than 1.2 x 10(6)/kg CD34(+) cells (27 vs 14 days, P<0.001). Differences in
      neutrophil engraftment between groups were not clinically significant. Pre
      transplant cumulative doses of etoposide >750 mg/m(2) were associated with low
      CD34(+) cell collections on multivariate analysis. The actuarial incidence of
      transplant-related mortality (TRM) was 14% at 5 years. Pre-transplant cumulative
      doses of etoposide >350 mg/m(2) and previous administration of procarbazine were
      found to be independent prognostic factors for TRM.

PMID- 14730339
TI  - An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease
      after CD34+ selected autologous peripheral blood stem cell transplant in
      neuroblastoma.
AB  - The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases
      with the use of highly immunosuppressive therapies. Allogeneic BMT, especially
      supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD.
      Although the risk of EBV-LPD after autologous transplantation is low, case
      reports of this complication in the autologous setting exist. We report a higher
      incidence than previously described of EBV-LPD in children undergoing sequential
      high-dose chemotherapy supported with CD34 selected peripheral blood stem cells
      (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range
      1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on
      two trials of tandem autologous SCT in high-risk pediatric malignancies. Both
      studies employed five cycles of induction therapy, followed by tandem autologous
      PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48
      received unselected PBSC. All patients contracting LPD were from the CD34
      selected group. Treatment of EBV-LPD included rituximab in four out of five
      patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five
      patients. EBV-LPD resolved in four out of five patients. We conclude that the
      combination of tandem SCT and CD34 selection may have increased immunosuppression
      in these patients to a point where there is an elevated risk of EBV-LPD.

PMID- 14730340
TI  - Acute renal tubular necrosis due to grass carp ingestion in a myeloma patient
      after allogeneic stem cell transplantation.

PMID- 14730341
TI  - Reversible acute renal failure following single administration of fludarabine.

PMID- 14730343
TI  - Measurement of C-reactive protein in adults with febrile neutropenia after
      hematopoietic cell transplantation.
AB  - The aim of this study was to evaluate the usefulness of C-reactive protein (CRP)
      monitoring in the differential diagnosis and prognosis of febrile neutropenic
      episodes in hematopoietic cell transplantation (HCT). In all, 100 patients were
      enrolled in the study. The CRP was determined in serum every 48 h from admission
      until resolution of the febrile episode. All patients presented with fever during
      the post-HCT neutropenic period. The febrile episodes were classified as
      microbiologically documented infection in 32 cases, clinically documented
      infection in 27 patients and fever of unknown origin in 41 patients. The mean CRP
      values on the first day of fever in these three groups were similar (NS). On the
      fifth day of antibiotic treatment, 50 patients remained pyrexial. Of these, 41
      improved with modifications of antibiotherapy (mean CRP: 9.5 mg/dl; standard
      deviation (s.d.): 6.2) and nine died, five due to an infectious etiology (CRP: 21
      mg/dl; s.d.: 4.4; P<0.003) and four from other causes (CRP: 11 mg/dl; s.d.: 3.4).
      On multivariate analysis, the CRP on the fifth day of treatment was an
      independent prognostic factor for fatal outcome. We conclude that persistent
      elevation of the CRP is an independent factor predicting a fatal outcome in
      patients who remain febrile on the fifth day of antibiotherapy during neutropenic
      febrile episodes post-HCT.

PMID- 14730342
TI  - Lipid formulations of amphotericin B preserve and stabilize renal function in
      HSCT recipients.
AB  - The current study assessed renal function based on medical records in adult
      hematopoietic stem cell transplant (HSCT) recipients with proven or probable
      invasive fungal infection (IFI) transplanted between 1995 and 2000. We confirm
      that amphotericin B deoxycholate (AmB-d) is nephrotoxic in a large percentage of
      HSCT recipients. Due to nephrotoxicity, defined as serum creatinine (SCr) >2.5
      mg/dl or a 100% increase in SCr from baseline, 88% of patients treated with AmB-d
      were switched to a lipid formulation of amphotericin B (LFAB). In total, 53% of
      patients initiated on AmB-d were switched within the first week of therapy.
      Significantly more patients (70.6%) treated with AmB-d experienced a 100%
      increase in SCr from baseline compared to patients treated with either AmBisome
      (44.4%) or Abelcet (41.2%). A Cox Proportional Hazards Model revealed that,
      compared to patients initiated on AmBisome or Abelcet, the risk of nephrotoxicity
      (RR=1.5 vs AmBisome; RR=1.7 vs Abelcet), dialysis (RR=2.4 vs AmBisome; RR=1.4 vs
      Abelcet), and death (RR=2.0 vs AmBisome; RR=1.1 vs Abelcet) were all increased
      for patients initiated on AmB-d. Study results suggest that renal function
      improves and mortality declines when an LFAB is given to HSCT patients as initial
      therapy rather than as second-line therapy, the current practice.

PMID- 14730344
TI  - Angiomotin expression promotes hemangioendothelioma invasion.
AB  - Angiomotin was identified by its ability to bind angiostatin and has been shown
      to mediate its activity in vitro. The family of angiomotin-like protein consists
      of three members that have coiled-coil domains and conserved c-terminal PDZ
      binding motifs. We show here that expression of angiomotin in mouse aortic
      endothelial (MAE) cells results in stabilization of tubes in the Matrigel assay.
      Control tubes start to regress after 72 h, whereas MAE-angiomotin (MAE Amot)
      tubes were stable for over 30 days. In contrast, cells expressing a functional
      mutant lacking the PDZ protein interaction motif did not migrate and form tubes.
      Cells from the established tubes invaded into the solidified matrigel. We
      therefore tested whether angiomotin promotes endothelial invasion. In
      microcarrier-based invasion in vitro assay, angiomotin-expressing cells invaded
      collagen matrix and formed tube-like branches. This was confirmed in vivo as
      injection of MAE-Amot cells promoted tumor growth and invasion into surrounding
      muscle tissue. Injection of cells transfected with the functional mutant resulted
      in establishment of noninvasive tumors surrounded by a capsule of fibrous tissue.
      These tumors remained in constant size or dormant over 3 weeks. Zymogel analysis
      of the transfected cells did not reveal any differences in proteolytic activity.
      However, time-lapse photography showed a significant increase in random motility
      in MAE-Amot cells. We conclude that angiomotin may promote angiogenesis by both
      stimulating invasion as well as stabilizing established tubes.

PMID- 14730345
TI  - Thioredoxin, a regulator of gene expression.
AB  - Cancer cells have high levels of thioredoxin (Trx) and of glyceraldehyde 3
      phosphate dehydrogenase (GAPDH). Cells from patients with the cancer-prone
      disease Fanconi anemia (FA) exhibit reduced Trx levels. We found the activity of
      GAPDH to correlate directly with the endogenous Trx content and mRNA transcripts
      for GAPDH and TRx reduced in FA cells. The treatment of cells with reduced human
      Trx stimulated the synthesis of GAPDH mRNA. Similarly, the transfection of cells
      with an expression plasmid for Trx increased GAPDH mRNA synthesis. Trx treatment
      of cells and subsequent analysis of the differential gene expression by human
      cDNA arrays containing about 50 000 different PCR products resulted in more than
      300 up- or downregulated genes. Two representative genes, GAPDH and
      IkappaBalpha/MAD-3, were further investigated to confirm their stimulation by
      Trx. Trx besides being the major carrier of redox potential of cells is also a
      regulator of gene expression on the transcriptional level. By regulation via Trx,
      cells are able to adapt to the prevailing redox conditions. These findings also
      enlighten the pathophysiology of FA in the respect that the characteristic
      diminution of Trx that results in the dysregulation of gene expression is a basis
      for the major symptoms of this disease.

PMID- 14730346
TI  - Blockade of cathepsin B expression in human glioblastoma cells is associated with
      suppression of angiogenesis.
AB  - The cysteine proteinase cathepsin B has been implicated in tumor progression by
      virtue of its increased mRNA and protein levels, as well as its localization at
      the invading front of the tumor. In this study, we examined whether blocking
      cathepsin B expression in human glioblastoma SNB19 cells affects angiogenesis.
      Stable transfectants of human glioblastoma cells with a plasmid containing
      antisense cathepsin B cDNA showed decreased migration rates in wound- and
      spheroid-migration assays. Analysis showed a reduction in VEGF protein and MMP-9
      activity in the cathepsin B antisense cDNA-transfected cells. Regarding
      angiogenesis in vitro, we found that the conditioned medium of glioblastoma cells
      with downregulated cathepsin B expression reduced cell-cell interaction of human
      microvascular endothelial cells, resulting in the disruption of capillary-like
      network formation. Furthermore, a marked reduction in microvasculature
      development was seen in an in vivo dorsal air sac assay of glioblastoma cells
      with downregulated cathepsin B expression. Taken together, these results provide
      evidence that inhibition of cathepsin B expression can suppress glioblastoma
      induced neovascularization.

PMID- 14730347
TI  - Frameshift mutation in the Dok1 gene in chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a malignant disease characterized
      by an accumulation of monoclonal CD5+ mature B cells, with a high percentage of
      cells arrested in the G0/G1 phase of the cell cycle, and a particular resistance
      toward apoptosis-inducing agents. Dok1 (downstream of tyrosine kinases) is an
      abundant Ras-GTPase-activating protein (Ras-GAP)-associated tyrosine kinase
      substrate, which negatively regulates cell proliferation, downregulates MAP
      kinase activation and promotes cell migration. The gene encoding Dok1 maps to
      human chromosome 2p13, a region previously found to be rearranged in B-CLL. We
      have screened the Dok1 gene for mutations from 46 individuals with B-CLL using
      heteroduplex analysis. A four-nucleotide GGCC deletion in the coding region was
      found in the leukemia cells from one patient. This mutation causes a frameshift
      leading to protein truncation at the carboxyl-terminus, with the acquisition of a
      novel amino-acid sequence. In contrast to the wild-type Dok1 protein, which has
      cytoplasmic/membrane localization, the mutant Dok1 is a nuclear protein
      containing a functional bipartite nuclear localization signal. Whereas
      overexpression of wild-type Dok1 inhibited PDGF-induced MAP kinase activation,
      this inhibition was not observed with the mutant Dok1. Furthermore the mutant
      Dok1 forms heterodimers with Dok1 wild type and the association can be enhanced
      by Lck-mediated tyrosine-phosphorylation. This is the first example of a Dok1
      mutation in B-CLL and the data suggest that Dok1 might play a role in
      leukemogenesis.

PMID- 14730348
TI  - The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase
      modifies substrates distant to local changes in glycoprotein conformation.
AB  - We present in vitro data that explain the recognition mechanism of misfolded
      glycoproteins by UDP-glucose glycoprotein-glucosyltransferase (UGGT). The
      glycoprotein exo-(1,3)-beta-glucanase (beta-Glc) bearing two glycans unfolds in a
      pH-dependent manner to become a misfolded substrate for UGGT. In the crystal
      structure of this glycoprotein, the local hydrophobicity surrounding each
      glycosylation site coincides with the differential recognition of N-linked
      glycans by UGGT. We introduced a single F280S point mutation, producing a beta
      Glc protein with full enzymatic activity that was both recognized as misfolded
      and monoglucosylated by UGGT. Contrary to current views, these data show that
      UGGT can modify N-linked glycans positioned at least 40 A from localized regions
      of disorder and sense subtle conformational changes within structurally compact,
      enzymatically active glycoprotein substrates.

PMID- 14730349
TI  - Crystal structure of MO25 alpha in complex with the C terminus of the pseudo
      kinase STE20-related adaptor.
AB  - Mouse protein 25 alpha (MO25 alpha) is a 40-kDa protein that, together with the
      STE20-related adaptor-alpha (STRAD alpha) pseudo kinase, forms a regulatory
      complex capable of stimulating the activity of the LKB1 tumor suppressor protein
      kinase. The latter is mutated in the inherited Peutz-Jeghers cancer syndrome
      (PJS). MO25 alpha binds directly to a conserved Trp-Glu-Phe sequence at the STRAD
      alpha C terminus, markedly enhancing binding of STRAD alpha to LKB1 and
      increasing LKB1 catalytic activity. The MO25 alpha crystal structure reveals a
      helical repeat fold, distantly related to the Armadillo proteins. A complex with
      the STRAD alpha peptide reveals a hydrophobic pocket that is involved in a unique
      and specific interaction with the Trp-Glu-Phe motif, further supported by
      mutagenesis studies. The data represent a first step toward structural analysis
      of the LKB1-STRAD-MO25 complex, and suggests that MO25 alpha is a scaffold
      protein to which other regions of STRAD-LKB1, cellular LKB1 substrates or
      regulatory components could bind.

PMID- 14730350
TI  - Proton-powered subunit rotation in single membrane-bound F0F1-ATP synthase.
AB  - Synthesis of ATP from ADP and phosphate, catalyzed by F(0)F(1)-ATP synthases, is
      the most abundant physiological reaction in almost any cell. F(0)F(1)-ATP
      synthases are membrane-bound enzymes that use the energy derived from an
      electrochemical proton gradient for ATP formation. We incorporated double-labeled
      F(0)F(1)-ATP synthases from Escherichia coli into liposomes and measured single
      molecule fluorescence resonance energy transfer (FRET) during ATP synthesis and
      hydrolysis. The gamma subunit rotates stepwise during proton transport-powered
      ATP synthesis, showing three distinct distances to the b subunits in repeating
      sequences. The average durations of these steps correspond to catalytic turnover
      times upon ATP synthesis as well as ATP hydrolysis. The direction of rotation
      during ATP synthesis is opposite to that of ATP hydrolysis.

PMID- 14730351
TI  - Mapping structural differences between 30S ribosomal subunit assembly
      intermediates.
AB  - Under appropriate conditions, functional Escherichia coli 30S ribosomal subunits
      assemble in vitro from purified components. However, at low temperatures,
      assembly stalls, producing an intermediate (RI) that sediments at 21S and is
      composed of 16S ribosomal RNA (rRNA) and a subset of ribosomal proteins (r
      proteins). Incubation of RI at elevated temperatures produces a particle, RI*, of
      similar composition but different sedimentation coefficient (26S). Once formed,
      RI* rapidly associates with the remaining r-proteins to produce mature 30S
      subunits. To understand the nature of this transition from RI to RI*, changes in
      the reactivity of 16S rRNA between these two states were monitored by chemical
      modification and primer extension analysis. Evaluation of this data using
      structural and biochemical information reveals that many changes are r-protein
      dependent and some are clustered in functional regions, suggesting that this
      transition is an important step in functional 30S subunit formation.

PMID- 14730352
TI  - Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in
      complex with a substrate analog.
AB  - Sialic acid terminates oligosaccharide chains on mammalian and microbial cell
      surfaces, playing critical roles in recognition and adherence. The enzymes that
      transfer the sialic acid moiety from cytidine-5'-monophospho-N-acetyl-neuraminic
      acid (CMP-NeuAc) to the terminal positions of these key glycoconjugates are known
      as sialyltransferases. Despite their important biological roles, little is
      understood about the mechanism or molecular structure of these membrane
      associated enzymes. We report the first structure of a sialyltransferase, that of
      CstII from Campylobacter jejuni, a highly prevalent foodborne pathogen. Our
      structural, mutagenesis and kinetic data provide support for a novel mode of
      substrate binding and glycosyl transfer mechanism, including essential roles of a
      histidine (general base) and two tyrosine residues (coordination of the phosphate
      leaving group). This work provides a framework for understanding the activity of
      several sialyltransferases, from bacterial to human, and for the structure-based
      design of specific inhibitors.

PMID- 14730353
TI  - Chemomechanical coupling in F1-ATPase revealed by simultaneous observation of
      nucleotide kinetics and rotation.
AB  - F(1)-ATPase is a rotary molecular motor in which unidirectional rotation of the
      central gamma subunit is powered by ATP hydrolysis in three catalytic sites
      arranged 120 degrees apart around gamma. To study how hydrolysis reactions
      produce mechanical rotation, we observed rotation under an optical microscope to
      see which of the three sites bound and released a fluorescent ATP analog.
      Assuming that the analog mimics authentic ATP, the following scheme emerges: (i)
      in the ATP-waiting state, one site, dictated by the orientation of gamma, is
      empty, whereas the other two bind a nucleotide; (ii) ATP binding to the empty
      site drives an approximately 80 degrees rotation of gamma; (iii) this triggers a
      reaction(s), hydrolysis and/or phosphate release, but not ADP release in the site
      that bound ATP one step earlier; (iv) completion of this reaction induces further
      approximately 40 degrees rotation.

PMID- 14730354
TI  - A short peptide insertion crucial for angiostatic activity of human tryptophanyl
      tRNA synthetase.
AB  - Human tryptophanyl-tRNA synthetase (TrpRS) is secreted into the extracellular
      region of vascular endothelial cells. The splice variant form (mini TrpRS)
      functions in vascular endothelial cell apoptosis as an angiostatic cytokine. In
      contrast, the closely related human tyrosyl-tRNA synthetase (TyrRS) functions as
      an angiogenic cytokine in its truncated form (mini TyrRS). Here, we determined
      the crystal structure of human mini TrpRS at a resolution of 2.3 A and compared
      the structure with those of prokaryotic TrpRS and human mini TyrRS. Deletion of
      the tRNA anticodon-binding (TAB) domain insertion, consisting of eight residues
      in the human TrpRS, abolished the enzyme's apoptotic activity for endothelial
      cells, whereas its translational catalysis and cell-binding activities remained
      unchanged. Thus, we have identified the inserted peptide motif that activates the
      angiostatic signaling.

PMID- 14730355
TI  - Structure of a bifunctional DNA primase-polymerase.
AB  - Genome replication generally requires primases, which synthesize an initial
      oligonucleotide primer, and DNA polymerases, which elongate the primer. Primase
      and DNA polymerase activities are combined, however, in newly identified
      replicases from archaeal plasmids, such as pRN1 from Sulfolobus islandicus. Here
      we present a structure-function analysis of the pRN1 primase-polymerase (prim
      pol) domain. The crystal structure shows a central depression lined by conserved
      residues. Mutations on one side of the depression reduce DNA affinity. On the
      opposite side of the depression cluster three acidic residues and a histidine,
      which are required for primase and DNA polymerase activity. One acidic residue
      binds a manganese ion, suggestive of a metal-dependent catalytic mechanism. The
      structure does not show any similarity to DNA polymerases, but is distantly
      related to archaeal and eukaryotic primases, with corresponding active-site
      residues. We propose that archaeal and eukaryotic primases and the prim-pol
      domain have a common evolutionary ancestor, a bifunctional replicase for small
      DNA genomes.

PMID- 14730356
TI  - Van der Waals versus dipolar forces controlling mesoscopic organizations of
      magnetic nanocrystals.
AB  - The structure, thermodynamics and dynamics in many physical and chemical systems
      are determined by interplay of short-range isotropic and long-range anisotropic
      forces. Magnetic nanoparticles dispersed in solution are ideal model systems to
      study this interplay, as they are subjected to both isotropic van der Waals and
      anisotropic dipolar forces. Here we show from experiment an abrupt transition of
      maghemite nanocrystal organization from chain-like to random structures when
      nanoparticle solutions are evaporated under a magnetic field. This is explained
      by brownian dynamics simulations in terms of a variation of the strength of van
      der Waals interactions with the particle contact distance, which is tuned by the
      length of the molecules coating the particles. The weak dipole-dipole
      interactions between the maghemite particles are usually not sufficient to result
      in the chain formation observed here. However, due to the van der Waals
      interactions, when the nanocrystal contact distance is short enough, clusters of
      nanocrystals are formed during the evaporation process. These clusters exhibit
      large dipole moments compared with a single particle, which explains the
      formation of chain-like structures. Conversely, when the nanocrystal contact
      distance is too long, no nanocrystal aggregation occurs, and a random
      distribution of maghemite nanocrystals is obtained.

PMID- 14730357
TI  - Impact of misfit dislocations on the polarization instability of epitaxial
      nanostructured ferroelectric perovskites.
AB  - Defects exist in almost all materials and defect engineering at the atomic level
      is part of modern semiconductor technology. Defects and their long-range strain
      fields can have a negative impact on the host materials. In materials with
      confined dimensions, the influence of defects can be even more pronounced due to
      the enhanced relative volume of the 'defective' regions. Here we report the
      dislocation-induced polarization instability of (001)-oriented
      Pb(Zr(0.52)Ti(0.48))O(3) (PZT) nanoislands, with an average height of
      approximately 9 nm, grown on compressive perovskite substrates. Using
      quantitative high-resolution electron microscopy, we visualize the strain fields
      of edge-type misfit dislocations, extending predominantly into a PZT region with
      a height of approximately 4 nm and width of approximately 8 nm. The lattice
      within this region deviates from the regular crystal structure. Piezoresponse
      force microscopy indicates that such PZT nanoislands do not show
      ferroelectricity. Our results suggest that misfit engineering is indispensable
      for obtaining nanostructured ferroelectrics with stable polarization.

PMID- 14730358
TI  - HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral
      replication.
AB  - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous
      virus-specific host immune response, and causes adult T-cell leukemia and
      lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1
      has evolved a genetic function to restrict its own replication by a novel post
      transcriptional mechanism. The HTLV-1-encoded p30(II) is a nuclear-resident
      protein that binds to, and retains in the nucleus, the doubly spliced mRNA
      encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of
      viral gene expression, their inhibition by p30(II) reduces virion production.
      p30(II) inhibits virus expression by reducing Tax and Rex protein expression.

PMID- 14730359
TI  - Trehalose alleviates polyglutamine-mediated pathology in a mouse model of
      Huntington disease.
AB  - Inhibition of polyglutamine-induced protein aggregation could provide treatment
      options for polyglutamine diseases such as Huntington disease. Here we showed
      through in vitro screening studies that various disaccharides can inhibit
      polyglutamine-mediated protein aggregation. We also found that various
      disaccharides reduced polyglutamine aggregates and increased survival in a
      cellular model of Huntington disease. Oral administration of trehalose, the most
      effective of these disaccharides, decreased polyglutamine aggregates in cerebrum
      and liver, improved motor dysfunction and extended lifespan in a transgenic mouse
      model of Huntington disease. We suggest that these beneficial effects are the
      result of trehalose binding to expanded polyglutamines and stabilizing the
      partially unfolded polyglutamine-containing protein. Lack of toxicity and high
      solubility, coupled with efficacy upon oral administration, make trehalose
      promising as a therapeutic drug or lead compound for the treatment of
      polyglutamine diseases. The saccharide-polyglutamine interaction identified here
      thus provides a new therapeutic strategy for polyglutamine diseases.

PMID- 14730360
TI  - TRADD interacts with STAT1-alpha and influences interferon-gamma signaling.
AB  - Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD)
      is essential in recruiting signaling molecules to the TNFR1 receptor complex.
      Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal
      transducer and activator of transcription 1-alpha (STAT1-alpha) for signal
      transduction. Here we demonstrate that IFN-gamma induces the formation of a
      nuclear-localized TRADD-STAT1-alpha complex. IFN-gamma-mediated STAT1-alpha
      phosphorylation was prolonged in cells with reduced TRADD expression. Moreover,
      we noted an increase in IFN-gamma-mediated STAT1-alpha DNA-binding activity,
      nuclear presence and transcriptional potential in the TRADD knockdown cells.
      These data indicate that TRADD may be involved in IFN-gamma signaling by forming
      a complex with STAT1-alpha within the nucleus and regulating IFN-gamma-mediated
      STAT1-alpha activation.

PMID- 14730361
TI  - The costimulation-regulated duration of PKB activation controls T cell longevity.
AB  - A brief antigenic stimulus can promote T cell proliferation, but the duration and
      nature of intracellular signals required for survival are unclear. Here we show
      that in the absence of OX40 costimulation, antigen-activated CD4+ cells are short
      lived because the activity of protein kinase B (PKB; also known as Akt) is not
      maintained over time. Activated T cells that express a dominant-negative variant
      of PKB also undergo apoptosis, reproducing the OX40-deficient phenotype. In
      contrast, an active form of PKB prevents downregulation of antiapoptotic proteins
      in OX40-deficient T cells, rescues antigen-induced cell survival in vivo, and
      controls inflammation in recall responses. Thus, sustained and periodic PKB
      signaling has an integral role in regulating T cell longevity.

PMID- 14730362
TI  - Aging, nutrition and immune function.
AB  - Aging is usually associated with increase in chronic disease as well as
      infections and associated morbidity. This is often thought to be secondary to
      immunosenescence. Whether this decline in immune function with aging is due to
      the aging process per se or is secondary to poor health, inflammation, and other
      life style factors particularly suboptimal nutritional status is discussed. Aging
      is often associated with dysregulation of immune response even among healthy
      elderly; some of these changes may be secondary to deficiencies of macronutrients
      (energy and protein) and micronutrients (notably, vitamins B6, B12, and folic
      acid as well as iron and zinc). Older individuals often have multiple nutrient
      deficiencies because of physiological, social and economic factors. Nutrient
      supplementation is often accompanied by an improvement in immune function
      particularly in those who are nutrient-deficient. The long-term benefits of
      multinutrient supplements to healthy elderly not at risk for nutrient
      deficiencies, however, are currently not well-established. Priorities for future
      research and methodological considerations for future studies are discussed.

PMID- 14730363
TI  - Effects of aging on immune function.
AB  - A variety of changes are observed in the immune system in both animals and humans
      with increasing age. There is a decline in the functional capacity of the cell
      populations that mount generalized and focused immune responses, and decreasing
      production and response of these cells to regulatory signals and proteins. These
      changes translate into less effective innate and adaptive immune responses,
      increased reactivity against self-antigens in vivo, and an increased incidence of
      infection. There may also be an increased risk of mortality. The mechanisms
      underlying age-related changes in immune function are not fully understood, but
      are likely to be multifactorial, including environmental and behavioral factors
      that affect over-all immune function from the molecular level to that of the
      entire organism.

PMID- 14730364
TI  - The effect of aging on mucosal host defense.
AB  - Mucosal immune response is primed at birth and responses generated at this time
      support specific immunity in later life. Conversely development of mucosal immune
      response to new antigens is diminished in aging. Availability of key nutrients
      that are conditionally essential especially in the context of sub-acute
      infections may limit immune response. A critical hypothesis is that conditionally
      essential nutrient requirements are associated with aging and form the
      fundamental basis of observed immune senescence. Since mucosal immunity is
      modulated by the interaction of microflora with the gut immune system, it is
      likely that changes in the gut during aging affect this microenvironment.
      Probiotic lactic acid bacteria offer one approach to stimulating the
      gastrointestinal immune system thereby enhancing systemic as well as mucosal
      immune response in aging. The mechanisms of action appear to include specific
      stimulation of natural killer cells (NK) and the innate immune system.

PMID- 14730365
TI  - Nutrition: a major factor influencing immunity in the elderly.
AB  - This paper reviews recent findings on immune ageing. Ageing per se affects mainly
      cell-mediated immunity: decreases in mature T-cells (CD3+) partly compensated
      with increases in less mature T-cells (CD2+CD3-) are observed. In addition
      antigen pressure throughout life induces increases in memory T-cells (CD45R0+)
      and borderline decreases in CD8+ subsets. Those changes lead to lower
      proliferative ability. In contrast B-cell subsets and innate immunity are less
      affected with ageing. These changes are mainly related to health status and are
      less important in very healthy elderly. Such changes are more important in
      undernourished elderly, and in elderly who exhibit decreases in micronutrient
      status. They are even stronger in elderly patients with protein energy
      malnutrition (PEM). In seniors with PEM, decreased immune functions, for all
      aspects of immunity, i.e. T-cell, B-cell subsets and functions and innate
      immunity, are strongly related to protein nutritional status. Refeeding can boost
      immune response but at a lower speed in patients exhibiting inflammatory process.
      The disequilibrium between normal macrophage functions and decreased T-cell
      functions is partly responsible for long-lasting inflammatory process in stressed
      patients. Therefore acute phase responses are more detrimental on nutritional
      status and nutrient reserves in aged patients than in adults. Such
      disequilibrium, stress after stress, pushes the elderly to frailty state.

PMID- 14730366
TI  - Influence of caloric restriction on aging immune system.
AB  - Nutrition has been shown to have a significant impact on aging. Caloric
      Restriction (CR), i.e., undernutrition not malnutrition, significantly increases
      the survival of laboratory animals by retarding/delaying the aging process. CR
      has beneficial effects on various physiological systems, including the immune
      system. Overall, the immunological status of rodents fed a restricted diet is
      superior to the immunological status of the non-restricted animals. It is
      believed that CR might retard aging and immunosenescence through a mechanism
      involving changes in signal transduction and gene expression. Recent studies from
      our laboratory support the view that the mechanism of CR involves changes in the
      activation of the upstream signaling molecules and cytokine gene expression that
      are altered with age.

PMID- 14730367
TI  - Influence of zinc on immunity in the elderly.
AB  - There is compelling evidence that demonstrates that severe zinc deficiency can
      cause substantial impairment of cellular immunity which can result in infection
      and even death. The effects on immunity of mild to moderate zinc deficiency are
      considerably less severe and may be subtle. Zinc supplementation, especially in
      combination with other micronutrients, can enhance immunity if an underlying
      deficiency is present. Supplementation with zinc as a single nutrient, especially
      at high doses, can have adverse effects that include interfering with copper
      nutriture and impairment of immune functions.

PMID- 14730368
TI  - The many roles of apoptosis in immunity as modified by aging and nutritional
      status.
AB  - Apoptosis plays a vital role in the elimination of anti-self clones, down
      regulation of immune responses and the killing of virally infected and malignant
      cells. There is ample evidence that as we age the immune system not only becomes
      less potent, but dysregulated which includes apoptotic dependent functions.
      Reductions in the production of naive T and B-cells, reduced cytolytic killing
      capacity, accumulation of larger numbers of malignant cells, enhanced
      inflammatory responses, etc., in the aged suggest that apoptosis is dysregulated.
      Changes in nutritional status can also alter apoptosis. A short period of zinc
      deficiency (ZD) in young adult mice greatly accelerated apoptosis among pre-B and
      pre-T cells by 50% to 300% providing a mechanistic explanation for the
      lymphopenia and thymic atrophy long associated with this and other nutritional
      deficiencies. Since apoptosis has been shown to be altered by aging and
      nutritional status, it seemed important to determine how ZD affected these
      processes in the aged mouse. It was quickly discovered that the pre-B cells were
      reduced by 80% in the 28 month aged mouse making further studies problematic. In
      marked contrast to suboptimal zinc, caloric restriction (CR) which when initiated
      in younger mice delayed the onset of autoimmunity and immunosenescence. CR
      appeared to also slow the aging of mitochondria and, thereby, reduced the release
      of reactive oxygen species that damage cells. Thus, it is probable that CR also
      helped maintain the integrity of mitochondria and apoptotic processes as mice
      aged. Though CR is not a very practical nutritional model for humans, the outcome
      of these studies reinforce the potential value of anti-oxidants in our diets. In
      contrast to their normal nutritional role some nutrients especially small amounts
      of free metals can induce apoptosis. There is considerable zinc in neurons. As
      will be discussed, a number of investigators think that this zinc is released
      during Alzheimer's, Parkinsons's, or brain injury and accelerates apoptosis in
      surrounding tissues causing greater damage. Data are discussed that indicate
      nanomoles of free zinc is, indeed, a potent inducer of apoptosis in a variety of
      tissues. In sum, there is no doubt that nutritional status as well as individual
      nutrients can modulate apoptosis and that their impact on cell death may become
      greater in the aged.

PMID- 14730369
TI  - Evaluation of hair fiber hydration by differential scanning calorimetry, gas
      chromatography, and sensory analysis.
AB  - Hair hydration is one of the effects that consumers most expect when using a
      cosmetic hair product. The purpose of this study was to combine differential
      scanning calorimetry (DSC) and gas chromatography (GC) techniques for a precise
      evaluation of the water content in hair fiber. DSC allowed determination of the
      bonding strength of water to hair fibers by quantifying the amount of energy
      required to remove the water. The amount of water thus removed was determined by
      GC. Post-treatment sensory evaluations of hair tresses were conducted to
      determine whether the values obtained with these techniques correspond to the
      moisturizing sensation perceived by consumers.

PMID- 14730370
TI  - Improving the aqueous solubility of triclosan by solubilization, complexation,
      and in situ salt formation.
AB  - Triclosan, an antimicrobial, although widely incorporated into many skin care
      products, toothpastes, and liquid soaps, presents formulation difficulties
      because it is practically insoluble in water. The objective of this study was to
      improve the aqueous solubility of triclosan through solubilization, complexation,
      and salt formation. The solubility of triclosan in distilled water and in
      phosphate buffers (pH 7.4) was determined at 30 degrees C. The order of
      solubilizing performance of the solubilizers was: N-methylglucamine> or =L
      arginine>sodium lauryl sulfate>beta-cyclodextrin> or =hydroxypropyl-beta
      cyclodextrin>ethanolamine>sodium benzoate>sodium methyl 4
      hydroxybenzoate>triethanolamine> or =diethanolamine. These solubilizers increased
      the solubility of triclosan from 80- to 6000-fold. Micellar solubilization and
      the formation of either salts or complexes are postulated as possible mechanisms
      for the increase in the solubility of triclosan by the surfactant sodium lauryl
      sulphate, the cyclic sugar derivatives beta-cyclodextrin and 2-hydropropyl-beta
      cyclodextrin, the amino acid L-arginine, and the amino sugar alcohol N
      methylglucamine. Furthermore, although the bacteriostatic efficacy of triclosan
      was significantly increased when solubilized with N-methylglucamine, L-arginine,
      and ethanolamine, increased solubilization did not increase the effectiveness of
      triclosan for all solubilizers tested.

PMID- 14730371
TI  - Comparison of antioxidant activity of extract from roots of licorice (Glycyrrhiza
      glabra L.) to commercial antioxidants in 2% hydroquinone cream.
AB  - Powdered dry roots of licorice (Glycyrrhiza glabra L.) were extracted with
      methanol. Licorice extract was tested for antioxidative activity in comparison
      with antioxidants (sodium metabisulfite and BHT) at 0.1%, 0.5%, 1.0%, and 2.0%
      w/w in 2% w/w hydroquinone cream. The systems were incubated in a dark room at 25
      degrees +/- 0.5 degrees C and 45 degrees +/- 0.5 degrees C for three months. The
      physical stability and the percentages of hydroquinone remaining after two weeks
      and one, two, and three months were determined by UV spectrophotometer at 294 nm
      according to official standard procedures. The experiment revealed that oxidation
      degradation of hydroquinone was accelerated by heat even with the existence of
      antioxidants. The higher percentages of remaining hydroquinone were observed for
      higher antioxidant concentration but showed lower physical stability in the
      formulation in the presence of commercial antioxidants, especially in the cases
      of 1.0% and 2.0% BHT. In the third month, at 25 degrees +/- 0.5 degrees C and 45
      degrees +/- 0.5 degrees C, the extract demonstrated more antioxidant activity
      from two other commercial antioxidants at all concentrations, with about 43-53%
      and 34-46%, respectively, more hydroquinone remaining than in the control system
      (p<0.001). In the third month, the preparation containing 0.1%, 0.5%, 1.0%, and
      2.0% extract gave good physical formulation stability with about 72%, 76%, 78%,
      and 81 % hydroquinone remaining at 25 degrees +/- 0.5 degrees C and 51%, 55%,
      60%, and 63% hydroquinone remaining at 45 degrees +/- 0.5 degrees C,
      respectively. This suggested the possibility of using a licorice extract at 0.5%
      and 1.0% as an effective natural antioxidant for substances that are oxidation
      susceptible.

PMID- 14730372
TI  - Solubilization of sodium cocoyl isethionate.
AB  - Sodium cocoyl isethionate (SCI) has been a predominant ingredient in syndet bar
      formulation for more than thirty years. Although cost effective and well
      recognized for good skin compatibility, SCI is not regularly found in liquid
      detergent systems due to its limited solubility in water. This study focuses on
      the understanding of enthalpy of solubilization, equilibrium of solubilization,
      and the structures and properties of sodium cocoyl isethionate and various
      surfactants. The purpose of this exercise is to help the formulator to find
      appropriate surfactant systems to keep sodium cocoyl isethionate in aqueous
      solution. The solubility of SCI in water is unfavorable in terms of enthalpy of
      solvation. When setting up equilibrium of solubilization, there are three
      possible phases, and three methods have been developed to prevent SCI from
      recrystallizing in aqueous solutions. The first focuses on tying CI ions within
      micelles made of secondary surfactants. The second focuses on the exchange of
      sodium ions with ammonium ions (and/or triethanolammonium). The third centers on
      emulsification of SCI and the subsequent change of micelles into emulsified oil
      drops. A combination of two or three of these methods will enable the formulator
      to use SCI as the primary surfactant in liquid detersive systems.

PMID- 14730373
TI  - Nano-structured biphasic polymer film on the hair surface from PEGylated polymer
      latexes.
AB  - In this study, biphasic polymer latexes were synthesized by surfactant-free
      emulsion polymerization of butyl methacrylate, poly(ethylene glycol) methyl ether
      methacrylate, and 2-(methacryloyloxy) ethyl trimethyl ammonium chloride. The
      latexes synthesized were composed of hydrophobic core phase and hydrophilic shell
      phase. Nano-structured film morphology could be obtained by annealing the
      biphasic polymer latexes between the two transition temperatures. It was found
      that the unique film morphology gave a viscoelastic property to the film.
      Scanning electron microscope and atomic force microscope images revealed that the
      biphasic polymer latexes deposited effectively onto the entire hair surface upon
      conditioning with 1 wt% polymer concentration in water. Consequently, they formed
      a smooth polymer membrane thereon, showing a high potential for a new hair
      cosmetic ingredient.

PMID- 14730374
TI  - Effects of conditioners on surface hardness of hair fibers: an investigation
      using atomic force microscopy.
AB  - Conditioners are known to have a prophylactic effect on hair damage caused by
      cosmetic chemical treatments or mechanical grooming procedures. They are known to
      impart softness and smoothness to hair by moisturizing the fiber. Since the
      amount of conditioners deposited on the fiber is very small in quantity, it is
      conceivable that mainly the surface is moisturized. This is especially true of
      polymeric conditioners, which deposit preferentially on the surface of the fiber,
      rather than penetrate into the cortex. Therefore, this study strictly
      investigates whether cationic polymeric conditioners impart softness to the
      surface cuticle cell as a result of their hydrophilicity, with no regard to its
      applicability to cosmetic effects. Such softening can be detected by indentation
      of the surface and can be quantified by measuring the depth of the indent in real
      time. Atomic force microscopy (AFM), equipped with nano-indentation capability,
      is ideally suited for this purpose. In this work it was used to determine changes
      in the microhardness (micromechanical properties) of the hair fiber surface as a
      result of fiber/conditioner/moisture interactions. In a preliminary study, we
      observed that the scale faces of hair treated with Polyquaternium 10 (PQ-10)
      conditioner gave deeper indents, while scale edges yielded shallower ones in
      comparison to cuticle cells of untreated hair. This suggests that the conditioner
      softens the scale face and hardens the scale edges. However, because of
      significant amounts of conditioner residues left on the scale face, this
      conclusion was rather ambiguous. Therefore, the study was repeated in which
      multiple indentations were made on the surface cuticle cells of a larger number
      of the same hair fibers before and after multiple applications of the
      conditioner. This reduces errors due to fiber-to-fiber variation in pre-existing
      microhardness differences in surface cuticle cells. Also, the larger number of
      fibers investigated in the current work allowed for a statistical outcome. This
      latter study has led to a rather definite conclusion that the scale face is
      indeed softened by polymeric conditioners such as Polyquaternium-10 (PQ-10).
      These studies will ultimately help in the development of conditioners with
      suitable moisturizing and softening effect on hair.

PMID- 14730375
TI  - Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV
      induced reactive oxygen species.
AB  - The ability of sunscreens and antioxidants to deactivate highly destructive
      reactive oxygen species in human skin has remained inconclusive. Two-photon
      fluorescence imaging microscopy was used to determine the effect of
      sunscreen/antioxidant combinations upon UV-induced ROS generation in ex vivo
      human skin. A sunscreen combination containing octylmethoxycinnamate (Parsol MCX)
      and avobenzone (Parsol 1789) at SPF 8 and SPF 15 was tested for its ability to
      prevent UV radiation from generating ROS in the viable epidermal strata of ex
      vivo human skin. A UV dose equivalent to two hours of North American solar UV was
      used to irradiate the skin. Each sunscreen reduced the amount of ROS induced in
      the viable strata by a value consistent with the SPF level. UV photons that were
      not absorbed/scattered by the sunscreen formulations generated ROS within the
      viable epidermal layers. The addition of the bioconvertible antioxidants vitamin
      E acetate and sodium ascorbyl phosphate (STAY-C 50) improves photoprotection by
      converting to vitamins E and C, respectively, within the skin. The bioconversion
      forms an antioxidant reservoir that deactivates the ROS generated (within the
      strata granulosum, spinosum, and basale) by the UV photons that the sunscreens do
      not block in the stratum corneum.

PMID- 14730376
TI  - Different techniques to measure intra-abdominal pressure (IAP): time for a
      critical re-appraisal.
AB  - The diagnosis of intra-abdominal hypertension (IAH) or abdominal compartment
      syndrome (ACS) is heavily dependent on the reproducibility of the intra-abdominal
      pressure (IAP) measurement technique. Recent studies have shown that a clinical
      estimation of IAP by abdominal girth or by examiner's feel of the tenseness of
      the abdomen is far from accurate, with a sensitivity of around 40%. Consequently,
      the IAP needs to be measured with a more accurate, reproducible and reliable
      tool. The role of the intra-vesical pressure (IVP) as the gold standard for IAP
      has become a matter of debate. This review will focus on the previously described
      indirect IAP measurement techniques and will suggest new revised methods of IVP
      measurement less prone to error. Cost-effective manometry screening techniques
      will be discussed, as well as some options for the future with microchip
      transducers.

PMID- 14730378
TI  - Effects of insulin-sensitising agents in mice with hepatic insulin resistance.
AB  - AIMS/HYPOTHESIS: The metabolic abnormalities of insulin resistance are
      ameliorated by insulin sensitisers via different mechanisms. Metformin decreases
      hepatic glucose output, whereas rosiglitazone (RSG) is an agonist for peroxisome
      proliferator activated receptor (PPAR)gamma, highly expressed in fat. To gain
      insight into the mechanisms of action of these drugs, we compared their actions
      in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and
      the liver specific insulin receptor knockout (LIRKO) mouse. METHODS: Control,
      ob/ob, and LIRKO mice were divided into three groups that received metformin (300
      mg/kg body weight/day), RSG (3 mg/kg body weight/day), or placebo for 3 weeks.
      RESULTS: In the presence of the severe hepatic insulin resistance of the LIRKO
      mouse, neither metformin nor RSG had any significant effect on glucose or insulin
      tolerance tests. On the other hand, RSG decreased serum concentrations of total
      cholesterol, LDL, and HDL in LIRKO mice. Adipocyte PPARgamma gene and protein
      expression, and adipocyte size were all increased in LIRKO mice treated with RSG,
      whereas fat-cell size in control animals was decreased by RSG.
      CONCLUSION/INTERPRETATION: TZDs probably improve some lipid parameters of the
      dysmetabolic syndrome associated with diabetes mellitus even in the presence of
      absolute hepatic insulin resistance, but both metformin and TZDs require an
      operating insulin signalling system in the liver for their effects in glucose
      homeostasis.

PMID- 14730377
TI  - Nutritional habits of subjects with Type 2 diabetes mellitus in the Mediterranean
      Basin: comparison with the non-diabetic population and the dietary
      recommendations. Multi-Centre Study of the Mediterranean Group for the Study of
      Diabetes (MGSD).
AB  - AIMS/HYPOTHESIS: The aim of this study was to compare the nutritional habits of
      Type 2 diabetic patients among Mediterranean countries and also with those of
      their background population and with the nutritional recommendations of the
      Diabetes and Nutrition Study Group. METHODS: We did a cross-sectional study of
      1833 non-diabetic subjects and 1895 patients with Type 2 diabetes, in nine
      centres in six Mediterranean countries. A dietary questionnaire validated against
      the 3-Day Diet Diary was used. RESULTS: In diabetic patients the contribution of
      proteins, carbohydrates and fat to the energy intake varied greatly among
      centres, ranging from 17.6% to 21.0% for protein, from 37.7% to 53.0% for
      carbohydrates and from 27.2% to 40.8% for fat, following in every centre the
      trends of the non-diabetic population. Furthermore, diabetic patients compared to
      the corresponding background population had: (i). lower energy intake, (ii).
      lower carbohydrate and higher protein contribution to the energy intake, (iii).
      higher prevalence of obesity, ranging from 9 to 50%. The adherence to the
      nutritional recommendations for proteins, carbohydrate and fat was very low
      ranging from 1.4 to 23.6%, and still decreased when fibre was also considered.
      CONCLUSION/INTERPRETATION: In diabetic patients of the Mediterranean area: (i).
      dietary habits vary greatly among countries, according to the same trends of the
      background population; (ii). the prevalence of obesity is much lower than the 80%
      reported for patients with diabetes in Western countries; (iii). Carbohydrate
      intake is decreased with a complementary increase of protein and fat consumption,
      resulting to a poor compliance with the nutritional recommendations.

PMID- 14730379
TI  - Multifactor-dimensionality reduction shows a two-locus interaction associated
      with Type 2 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes mellitus is a complex genetic disease, which
      results from interactions between multiple genes and environmental factors
      without any single factor having strong independent effects. This study was done
      to identify gene to gene interactions which could be associated with the risk of
      Type 2 diabetes. METHODS: We genotyped 23 different loci in the 15 candidate
      genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non
      diabetic control subjects. We analysed gene to gene interactions among 23
      polymorphic loci using the multifactor-dimensionality reduction (MDR) method,
      which has been shown to be effective for detecting and characterising gene to
      gene interactions in case-control studies with relatively small samples. RESULTS:
      The MDR analysis showed a significant gene to gene interaction between the
      Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T
      polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma (
      PPARgamma) gene. This interaction showed the maximum consistency and minimum
      prediction error among all gene to gene interaction models evaluated. Moreover,
      the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C
      homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio:
      0.51, 95% CI: 0.34 to 0.77, p=0.0016). CONCLUSIONS/INTERPRETATION: Using the MDR
      method, we showed a two-locus interaction between the UCP2 and PPARgamma genes
      among 23 loci in the candidate genes of Type 2 diabetes. The determination of
      such genotype combinations contributing to Type 2 diabetes mellitus could provide
      a new tool for identifying high-risk individuals.

PMID- 14730380
TI  - The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation
      in insulin-resistant skeletal muscle in lean and obese Zucker rats.
AB  - AIMS/HYPOTHESIS: Recruitment of the protein c-Cbl to the insulin receptor (IR)
      and its tyrosine phosphorylation via a pathway that is independent from
      phosphatidylinositol 3'-kinase is necessary for insulin-stimulated GLUT4
      translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or
      exercise has yet to be reported in skeletal muscle. METHODS: Lean and obese
      Zucker rats were randomly assigned to one of three treatment groups: (i).
      control, (ii). insulin-stimulated or (iii). acute, exhaustive exercise. Hind limb
      skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl
      measured. RESULTS: Insulin receptor phosphorylation was increased 12-fold after
      insulin stimulation ( p<0.0001) in lean rats and threefold in obese rats. Acute
      exercise had no effect on IR tyrosine phosphorylation. Similar results were found
      for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine
      phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to
      previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after
      insulin treatment ( p<0.001). CONCLUSIONS/INTERPRETATION: We also found that c
      Cbl associating protein expression is relatively low in skeletal muscle of Zucker
      rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl
      tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of
      c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin
      resistant Zucker rats ( p<0.05), but the physiological relevance is not clear. We
      conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs
      from that previously reported in adipocytes.

PMID- 14730381
TI  - Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes
      with susceptibility to Type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The Pro12Ala polymorphism of peroxisome proliferator-activated
      receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The
      rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes
      by 20 percent. This variant is in linkage disequilibrium with another common
      variant, T1431. Both have opposing associations with body weight. We therefore
      examined the association of specific haplotypes marked by these two variants with
      susceptibility to Type 2 diabetes. METHODS: We determined the PPARG genotype of a
      large Scottish cohort of Type 2 diabetic patients ( n=1997) and compared allele
      frequencies with a cohort of local children ( n=2444) and a middle-aged,
      population-based cohort from Scotland ( n=1061). RESULTS: Frequency of the Ala12
      allele was slightly lower in the Type 2 diabetic cohort than in the children
      [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under
      represented in the Type 2 diabetic population when compared with similarly aged
      non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a
      haplotype not bearing the 1431T variant, it conferred greater protection
      (OR=0.66, p=0.003). However, when it was present in haplotypes containing the
      1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99,
      p=0.94). CONCLUSIONS/INTERPRETATION: We replicated the finding that the Ala12
      variant of PPARgamma affords protection from Type 2 diabetes, and suggest that
      this protection is modulated by additional common variation at the PPARG locus.

PMID- 14730382
TI  - Appendicitis in children less than 3 years of age: a 28-year review.
AB  - Appendicitis is the most common surgical abdominal emergency in the pediatric
      population, but is rarely considered in children less than 3 years of age. The
      goal of this study was to identify the presenting symptoms and signs in this age
      group and examine their subsequent management and outcome. A 28-year experience
      of a single pediatric surgeon in academic practice was reviewed; 27 children less
      than 3 years old (mean 23 months) comprised 2.3% of all children with
      appendicitis in his series. The most common presenting symptoms were vomiting
      (27), fever (23), pain (21), anorexia (15), and diarrhea (11). The average
      duration of symptoms was 3 days, with 4 or more days in 9 children. Eighteen
      children were seen by a physician before the correct diagnosis was made; 14 were
      initially treated for an upper respiratory tract infection, otitis media, or a
      urinary tract infection. The most common presenting signs were abdominal
      tenderness (27), peritonitis (24), temperature 38.0 degrees C or more (21),
      abdominal distension (18), Leukocytosis (<12.0 x 10(3)/mm(3)) was found in 18,
      tenderness was localized to the right lower quadrant (RLQ) in 14 and was diffuse
      in 10. Abdominal radiographs demonstrated findings of a small-bowel obstruction
      (SBO) in 14 of 21 patients, a fecalith in 2, and a pneumoperitoneum in 1.
      Contrast enemas were performed in 6 children, 5 of whom had a phlegmon or an
      abscess. Perforated appendicitis was found in all 27 patients. An appendectomy
      was performed in 25 and a RLQ drain was placed in 18. Postoperative antibiotics
      were administered to 17 children for an average of 6 days. Two patients underwent
      interval appendectomies, 1 following treatment with IV antibiotics and 1
      following surgical drainage. The average time to resume oral intake was 7 days
      and the average hospital stay was 21 (median 15) days. Sixteen patients had 22
      complications, which included 6 wound infections, 4 abscesses, 4 wound
      dehiscences, 3 pneumonias, 2 SBOs, 2 incisional hernias, and 1 enterocutaneous
      fistula. Perforated appendicitis was found in all children less than 3 years old,
      resulting in very high morbidity (59% complications), which may be attributed to
      the 3-5-day delay in diagnosis. Although appendicitis is uncommon in this age
      group, it should be seriously considered in the differential diagnosis of
      children under the age of 3 years who present with the triad of abdominal pain,
      tenderness, and vomiting.

PMID- 14730383
TI  - Julius Bruck (1840-1902) and his influence on the endoscopy of today.
AB  - A hundred years ago, on 20 April 1902, Breslaus most famous dentist of the time
      died. Julius Bruck was not only the most famous dentist and fighter for dentists'
      education in Germany in his time, but also one of the most successful inventors.
      In 1866, he produced light by using an exposed electrically heated platinum loop,
      which at that time was the most powerful light source known. He conceived of the
      possibility of placing the source of light in the distal end of an instrument and
      invented a double glass tube with a water-cooling compartment. This water cooled
      apparatus (diaphanoscope) was inserted into the rectum or vagina, to
      transilluminate the bladder. The key to further advances was born with the
      introduction of an internal electric light source. In 1877, the potential of
      Bruck's theoretical advance was realised in combination with other advances which
      virtually established the form of the clinically useful cystoscope as it is used
      today. The remarkable man responsible for this synthesis was Maximilian Nitze.

PMID- 14730384
TI  - Detection of colorectal liver metastases: a prospective multicenter trial
      comparing unenhanced MRI, MnDPDP-enhanced MRI, and spiral CT.
AB  - The aim of this study was to compare unenhanced MRI, MnDPDP-enhanced MRI, and
      spiral CT in the detection of hepatic colorectal metastases. Forty-four patients
      with hepatic colorectal metastases were examined with unenhanced and MnDPDP
      enhanced MRI and with unenhanced and contrast-enhanced spiral CT. The MR
      examination protocol included baseline T1-weighted spin-echo (SE), T1-weighted
      gradient-recalled-echo (GRE), and T2-weighted fast-SE sequences; and T1-weighted
      SE and T1-weighted GRE sequences obtained 30-60 min after administration of 0.5
      micromol/kg (0.5 ml/kg) mangafodipir trisodium (MnDPDP). Images were interpreted
      by three blinded readers. Findings at CT and MRI were compared with those at
      intraoperative US, which were used as term of reference. Intraoperative US
      detected 128 metastases. In a lesion-by-lesion analysis, the overall detection
      rate was 71% (91 of 128) for spiral CT, 72% (92 of 128) for unenhanced MRI, and
      90% (115 of 128) for MnDPDP-enhanced MRI. MnDPDP-enhanced MRI was more sensitive
      than either unenhanced MRI ( p<0.0001) or spiral CT ( p=0.0007). In a patient-by
      patient analysis, agreement with gold standard was higher for MnDPDP-enhanced MRI
      (33 of 44 cases) than for spiral CT (22 of 44 cases, p=0.0023) and unenhanced MRI
      (21 of 44 cases, p=0.0013). MnDPDP-enhanced MRI is superior to unenhanced MRI and
      spiral CT in the detection of hepatic colorectal metastases.

PMID- 14730385
TI  - Targeted cybridization in citrus: transfer of Satsuma cytoplasm to seedy
      cultivars for potential seedlessness.
AB  - CMS (cytoplasmic male sterility) can be controlled by the mitochondrion genome in
      higher plants, including Satsuma mandarin. Somatic fusion experiments in citrus
      combining embryogenic callus protoplasts of one parent with leaf protoplasts of a
      second parent often produce cybrid plants of the leaf parent, a phenomenon
      occurring most often with interspecific fusion combinations. In an attempt to
      practically exploit this cybridization phenomenon, we conducted somatic fusion
      experiments combining embryogenic suspension-derived protoplasts of Satsuma
      mandarin, Citrus unshiu Marc. cv. Guoqing No. 1 (G1), a male-sterile cultivar,
      with leaf protoplasts of other seedy types--Hirado Buntan Pink pummelo (HBP)
      [Citrus grandis (L.) Osbeck], Sunburst mandarin (C. reticulata Blanco), Orie Lee
      hybrid (C. reticulata cv. Clementine x Murcott tangor), and Murcott tangor [C.
      reticulata x C. sinensis (L.) Osbeck], respectively--in an attempt to generate
      seedless cybrids by the targeted transfer of CMS. The genetic identities of
      regenerated plants from all four parental combinations were determined by flow
      cytometry, SSR, CAPS (or PCR-RFLP), RFLP, and chloroplast-SSR analyses.
      Regenerated plants from the first three parental combinations were diploids, and
      the cybrid nature of G1 + HBP with the mitochondrion genome from G1 and the
      chloroplast genome from HBP was confirmed, whereas the cybrid nature of the
      remaining two combinations was difficult to confirm because of the close
      phylogenetic relatedness of both fusion parents, as expected. Plants from G1 +
      Murcott were confirmed as tetraploid somatic hybrids. This is the first report of
      targeted citrus cybrid production by symmetric fusion with male-sterile Satsuma
      as the callus parent and other seedy cultivars as the leaf parents.

PMID- 14730386
TI  - A Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index:
      reliability and validity.
AB  - The aim of this study was to develop a Turkish version of the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) and assess its reliability, validity,
      and sensitivity to change. The Turkish version was obtained after a translation
      and back-translation process. Seventy-one patients with ankylosing spondylitis
      were assessed with it. To assess its validity, patients were also evaluated with
      the Turkish version of the Bath Ankylosing Spondylitis Functional Index (BASFI),
      the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Bath Ankylosing
      Spondylitis Patient Global Score (BAS-G), and physicians' assessments of disease
      activity. Over 24 h, the Turkish BASDAI did not show significant differences
      between the two assessments (P>0.05). Correlations were found between BASDAI and
      all of the evaluation parameters except BASMI (P<0.01). Both BASDAI and BASMI
      showed significant improvements after 8-week home exercise programmes. The
      results of this study show that the Turkish version of the BASDAI is reliable,
      valid, and sensitive to change.

PMID- 14730390
TI  - NADPH oxidase is not required for spontaneous and Staphylococcus aureus-induced
      apoptosis of monocytes.
AB  - Reactive oxygen intermediates (ROI) generated in the respiratory burst reaction
      are crucial for the killing of bacteria and fungi in phagocytes. The key enzyme
      for the respiratory burst reaction is the NADPH oxidase. Reactive oxygen
      intermediates have additionally been proposed to be of general importance for the
      expression of FAS and soluble FAS ligand (sFASL) and the subsequent induction of
      apoptosis. This conclusion has been drawn from the observation that neutrophils
      with an inborn lack of the NADPH oxidase as well as cell lines and monocytes with
      artificially blocked NADPH oxidase exhibit impaired apoptosis. Being one of the
      few centers caring for patients with chronic granulomatous disease (CGD) who
      exhibit an inborn lack of NADPH oxidase, we had the unique opportunity to
      determine the role of the NADPH oxidase for apoptosis in monocytes with otherwise
      unmanipulated cells of these patients (CGD monocytes). We compared the expression
      of FAS on monocytes and the concentration of sFASL in the supernatant between CGD
      monocytes and healthy donors undergoing spontaneous apoptosis. Neither the
      expression of FAS nor the concentration of sFASL was decreased in CGD monocytes.
      We further compared spontaneous apoptosis and apoptosis occurring after the
      phagocytosis of Staphylococcus aureus in CGD monocytes to monocytes of healthy
      controls. In these experiments we could not determine any significant impairment
      of apoptosis in CGD monocytes. Our data indicate for the first time that in an
      unmanipulated human model a functional NADPH oxidase is not crucial for the
      apoptosis of monocytes and disprove a general role of ROI for the induction of
      apoptosis in phagocytes.

PMID- 14730391
TI  - Primary adrenal lymphoma presenting as Addison's disease: case report and review
      of the literature.
AB  - Primary adrenal lymphoma (PAL) is an extremely rare entity and adrenal
      insufficiency is a common complication. Bilateral enlargement of adrenal glands
      should raise the suspicion of lymphoma, especially in patients with clinical or
      laboratory features of adrenal insufficiency. Most of these cases are highly
      aggressive tumors and should be treated with multiagent chemotherapy. The role of
      bilateral adrenalectomy and/or radiotherapy cannot be estimated. Our patient with
      PAL was an 80-year-old man who presented with clinical and laboratory features of
      adrenal insufficiency. Combination chemotherapy plus rituximab was unsuccessful
      and our patient died from progressive disease.

PMID- 14730393
TI  - Late relapse of acute promyelocytic leukemia treated with all- trans retinoic
      acid and chemotherapy: report of two cases.
AB  - Two patients with acute promyelocytic leukemia (APL) relapsed at 111 and 84
      months after achievement of complete remission (CR) induced by a combination of
      all- trans retinoic acid and chemotherapy. In both patients molecular remission,
      obtained after consolidation, had been confirmed at 60 months from CR
      achievement. At relapse, morphological, immunophenotypic, cytogenetic, and
      molecular analyses showed findings identical to those at diagnosis. Hematological
      and molecular remission was induced with the identical treatment applied at
      diagnosis. We conclude that, although infrequently, patients with APL treated
      with modern combination therapy can experience very late relapse and can be
      rescued with treatment similar to that administered at diagnosis.

PMID- 14730392
TI  - Case of megaloblastic anemia caused by intestinal taeniasis.
AB  - A 61-year-old eutrophic male was diagnosed with vitamin B12 deficiency and
      megaloblastic anemia. A modified Schilling test suggested intestinal
      malabsorption unrelated to intrinsic factor deficiency. Subsequent colonoscopy
      revealed the presence of a Taenia tapeworm. The anemia resolved within days under
      therapy with niclosamide and temporary vitamin B12 supplements. The present case
      suggests that, in addition to other well-known parasitic agents, e.g.,
      Diphyllobothrium latum and Giardia lamblia, Taenia infestation can also be a
      cause of intestinal vitamin B12 malabsorption.

PMID- 14730394
TI  - The middle collateral artery: anatomic basis for the "extreme" lateral arm flap.
AB  - The vascularization of the posterolateral area of the arm is supplied by the
      terminal branches of the deep brachial artery [middle collateral artery (MCA) and
      posterior radial collateral artery]. Their anatomy has been a field of confusion
      for a long time. An extended lateral arm flap, named the "extreme" lateral arm
      flap, supplied by these branches and dissected as a retrograde island flap has
      been proposed as an alternative for large compound defects of the distal forearm.
      We carried out an extensive anatomic study of the "extreme" lateral arm flap on
      69 upper limbs: 54 fresh injected with colored latex, 10 embalmed and 5
      radiographed after Micropaque injection. Two origin levels of the MCA were found:
      a proximal one (37%) above the radial groove, and a distal one (63%) at the level
      of the groove. The deep brachial artery always bifurcated after the origin of the
      MCA into a posterior radial collateral artery (PRCA) and anterior radial
      collateral artery (ARCA). Indeed in our dissections, after the origin of the MCA
      from the deep brachial artery, there was always a common trunk named the radial
      collateral artery (RCA) which bifurcated into the ARCA and PRCA. In all dissected
      arms we always found the MCA anastomosed in a transverse pattern with the
      inferior ulnar collateral artery (IUCA), contributing to the anastomotic circle
      of the elbow. This circle represents the unique vascularization source of the
      reverse "extreme" lateral arm flap.

PMID- 14730395
TI  - The anatomical rationale for an upper limb sympathetic blockade: preliminary
      report.
AB  - Stellate ganglion blockade (SGB) has long been considered pivotal in the
      diagnosis, determination of prognosis and management of chronic regional pain
      syndrome (CRPS) by sympathectomy. To date a variety of SGB techniques have been
      described. An inaccurate SGB may mislead clinicians and deny patients a
      potentially beneficial procedure. In order to obtain a predictable and readily
      reproducible blockade of the upper limb, a modified anterior technique was
      evaluated. This modified sympathetic block was performed in 10 adult cadavers
      (n=19 sides). Toluidine blue solution (10 ml) was injected and, following median
      sternotomy, the extent of spread of dye was evaluated. In one cadaver a dual
      block using both the modified and the standard techniques was performed. Proximal
      spread to the seventh cervical vertebra was noted in all blocks; distal spread
      extended to the neck of the third rib (n=3), neck of the fourth rib 7 (n=15) and
      neck of the seventh rib (n=1). Medial spread was greater than lateral spread and
      extended to the vertebral bodies (vagus nerve was also stained) while lateral
      spread in all cases "blocked" lower roots of the brachial plexus and was
      consistently noted beyond the usual location of the nerve of Kuntz. This modified
      technique demonstrated that the lower cervical ganglia and proximal thoracic
      sympathetic trunk were consistently stained. It should be noted that the spread
      was sufficiently lateral to block the nerve of Kuntz. The pitfalls of this
      technique aside, we suggest that this technique be reserved for therapeutic
      purposes, particularly when sympathectomy is not possible.

PMID- 14730398
TI  - Prospective comparison of differences in bone mineral density adjacent to two
      biomechanically different types of cementless femoral stems.
AB  - We compared the differences in bone mineral density (BMD) adjacent to two
      biomechanically different cementless femoral stems (Spotorno and Evolution-K).
      Measurements were performed within the first week after surgery and 3, 6, 12, and
      24 months postoperatively in a prospective study of 31 patients with 37 total hip
      arthroplasties. A modified Harris hip score and a visual analogue score for
      patient satisfaction was used to evaluate the clinical outcome. For both stems,
      dual X-ray absorptiometry measurements revealed a decrease in BMD in Gruen zone
      7. Patients with a Spotorno stem also had a significant decrease in BMD in zones
      1 and 2. In patients with an Evolution-K stem, there was a positive correlation
      between the clinical outcome and BMD in Gruen zones 1 and 4. Our data suggest
      that periprosthetic bone loss is equal to if not less pronounced adjacent to the
      Evolution-K stem as compared to the Spotorno stem.

PMID- 14730399
TI  - Tetraspanins connect several types of Ig proteins: IgM is a novel component of
      the tetraspanin web on B-lymphoid cells.
AB  - The tetraspanins form a family of about 30 molecules mainly expressed on the cell
      surface. They have been reported to be involved in many physiological or
      pathological processes, such as fertilization, immune response, development of
      the nervous system, and metastasis, as well as in infectious diseases (HCV,
      malaria, etc.). The tetraspanins may play a role as "organizers" of
      multimolecular complexes on the cell surface associating numerous proteins, the
      "tetraspanin web." To better define the composition of the tetraspanin web, its
      characterization has been recently performed using mass spectrometry and
      proteomics. We report the proteomic analysis of tetraspanin complexes on B
      lymphoid cells. Immunoprecipitation experiments were performed using mAbs
      directed against the tetraspanin CD9, and associated molecules were identified by
      MALDI-TOF (matrix assisted laser desorption ionization time of flight) mass
      spectrometry. This led to the identification of IgM as a novel component of the
      complexes. Thus, tetraspanins may connect several types of proteins with Ig
      domains, including HLA-DR, EWI-2, and IgM, that may play a role in immune
      responses.

PMID- 14730400
TI  - MHC class II and CD80 tumor cell-based vaccines are potent activators of type 1
      CD4+ T lymphocytes provided they do not coexpress invariant chain.
AB  - We are developing vaccines that activate tumor-specific CD4+ T cells. The cell
      based vaccines consist of MHC class I+ tumor cells that are genetically modified
      to express syngeneic MHC class II and costimulatory molecules. Previous studies
      demonstrated that treatment of mice with established tumors with these vaccines
      resulted in regression of solid tumors, reduction of metastatic disease, and
      increased survival time. Optimal vaccines will prime naive T cells and activate T
      cells to tumor peptides derived from diverse subcellular compartments, since
      potential tumor antigens may reside in unique cellular locales. To determine if
      the MHC class II/costimulatory molecule vaccines fulfill these conditions, the
      vaccines have been tested for their ability to activate antigen-specific, naive,
      transgenic CD4+ T lymphocytes. MHC class II(+)CD80+ vaccine cells were
      transfected with hen eggwhite lysozyme targeted to the cytosol, nuclei,
      mitochondria, or endoplasmic reticulum, and used as antigen-presenting cells to
      activate I-Ak-restricted, lysozyme-specific CD4+ 3A9 transgenic T cells.
      Regardless of the cellular location of lysozyme, the vaccines stimulated release
      of high levels of IFN-gamma and IL-2. If the vaccines coexpressed the MHC class
      II accessory molecule invariant chain, then IFN-gamma and IL-2 release was
      significantly reduced. These studies demonstrate that in the absence of invariant
      chain the MHC class II and CD80 tumor cell vaccines (1) function as antigen
      presenting cells to activate naive, tumor-specific CD4+ cells to endogenously
      synthesized tumor antigens; (2) polarize the activated CD4+ T cells toward a type
      1 response; and (3) present epitopes derived from varied subcellular locales.

PMID- 14730401
TI  - The effect of aging on cellular immunity against cancer in SR/CR mice.
AB  - SR/CR mice are capable of mounting a highly effective response of leukocytes to
      large doses of lethal transplantable mouse cancer cells. This response is
      conferred by a dominant, germline-transmissible mutation independent of sex
      chromosomes. The resistance can be extended to a broad array of mouse and human
      cancer cells without harming normal cells. The effector cells are primarily
      composed of the leukocytes from the innate immune system including macrophages,
      neutrophils, and natural killer cells. The mice are cancer-free and healthy
      without detectable abnormality or shortened life span. However, the immune
      response mechanism of these SR/CR mice is dramatically modulated by the aging
      process. In this article, we summarize the lessons learned from these mice and
      discuss possible implications of these findings in our understanding of the
      effects of aging on the immunity against cancer.

PMID- 14730402
TI  - On the logic of hypothesis testing in functional imaging.
AB  - Statistics is nowadays the customary language of functional imaging. It is common
      to express an experimental setting as a set of null hypotheses over complex
      models and to present results as maps of p-values derived from sophisticated
      probability distributions. However, the growing interest in the development of
      advanced statistical algorithms is not always paralleled by similar attention to
      how these techniques may regiment the ways in which users draw inferences from
      their data. This article investigates the logical bases of current statistical
      approaches in functional imaging and probes their suitability to inductive
      inference in neuroscience. The frequentist approach to statistical inference is
      reviewed with attention to its two main constituents: Fisherian "significance
      testing" and Neyman-Pearson "hypothesis testing". It is shown that these
      conceptual systems, which are similar in the univariate testing case, dissociate
      into two quite different methods of inference when applied to the multiple
      testing problem, the typical framework of functional imaging. This difference is
      explained with reference to specific issues, like small volume correction, which
      are most likely to generate confusion in the practitioner. Further insight into
      this problem is achieved by recasting the multiple comparison problem into a
      multivariate Bayesian formulation. This formulation introduces a new perspective
      where the inferential process is more clearly defined in two distinct steps. The
      first one, inductive in form, uses exploratory techniques to acquire preliminary
      notions on the spatial patterns and the signal and noise characteristics. The
      (smaller) set of likely spatial patterns generated is then tested with newer data
      and a more rigorous multiple hypothesis testing technique (deductive step).

PMID- 14730403
TI  - Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG
      PET and 111In-granulocyte scintigraphy.
AB  - The diagnostic work-up in patients with fever of unknown origin (FUO) is often
      challenging and frequently includes nuclear medicine procedures. Whereas a role
      for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a
      possible role of fluorine-18 fluorodeoxyglucose (FDG) positron emission
      tomography (PET) in these patients remains to be established. To study this, we
      compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET
      and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients
      with FUO underwent both FDG-PET and (111)In-granulocyte scintigraphy within 1
      week. FDG-PET scans and granulocyte scintigrams were reviewed by different
      doctors who were blinded to the result of the other investigation. The diagnostic
      values of FDG-PET and granulocyte scintigraphy were evaluated with regard to
      identification of a focal infectious/inflammatory or malignant cause of FUO. The
      sensitivity of granulocyte scintigraphy and FDG-PET were 71% [95% confidence
      interval (CI): 37-85%] and 50% (CI: 16-84%), respectively. The specificity of
      granulocyte scintigraphy was 92% (71-100%), which was significantly higher than
      that of FDG-PET, at 46% (34-62%). Positive and negative predictive values for
      granulocyte scintigraphy were both 85%. Positive and negative predictive values
      for FDG-PET were 30% and 67%, respectively. (111)In-granulocyte scintigraphy has
      a superior diagnostic performance compared to FDG-PET for detection of a
      localised infectious/inflammatory or neoplastic cause of FUO. The poorer
      performance of FDG-PET is in particular attributable to a high percentage of
      false positive scans, leading to low specificity.

PMID- 14730404
TI  - The role of 18F-FDG PET in characterising disease activity in Takayasu arteritis.
AB  - Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis,
      which predominantly affects the aorta and its branches. Diagnosis can be
      difficult and there are limitations to the current diagnostic work-up. By
      detecting areas of active glucose metabolism present in active vasculitis,
      imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F
      FDG PET) could potentially have a role in the management of TA. Our aim was to
      assess this role by reviewing 28 (18)F-FDG PET scans performed on 18 patients
      suspected of having TA. All patients had full clinical and laboratory assessment,
      cross-sectional imaging and angiography, and 16/18 satisfied the American College
      of Rheumatologists' criteria for TA. (18)F-FDG PET achieved a sensitivity of 92%,
      a specificity of 100%, and negative and positive predictive values of 85% and
      100% respectively in the initial assessment of active vasculitis in TA. We
      conclude that (18)F-FDG PET can be used to diagnose early disease, to detect
      active disease (even within chronic changes) and to monitor the effectiveness of
      treatment.

PMID- 14730405
TI  - Database of normal human cerebral blood flow, cerebral blood volume, cerebral
      oxygen extraction fraction and cerebral metabolic rate of oxygen measured by
      positron emission tomography with 15O-labelled carbon dioxide or water, carbon
      monoxide and oxygen: a multicentre study in Japan.
AB  - Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral
      oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2))
      by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide
      (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide
      (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and
      treatment planning in cases of cerebrovascular disease. The measured values
      theoretically depend on various factors, which may differ between PET centres.
      This study explored the applicability of a database of (15)O-PET by examining
      between-centre and within-centre variation in values. Eleven PET centres
      participated in this multicentre study; seven used the steady-state inhalation
      method, one used build-up inhalation and three used bolus administration of
      C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV.
      Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/
      15.1 years). Overall mean+/-SD values for cerebral cortical regions were:
      CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/
      0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre
      variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance.
      However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was
      acceptably small. Building a database of normal cerebral haemodynamics obtained
      by the(15)O-PET methods may be practicable.

PMID- 14730406
TI  - Effect of scatter correction on the compartmental measurement of striatal and
      extrastriatal dopamine D2 receptors using [123I]epidepride SPET.
AB  - Prior studies with anthropomorphic phantoms and single, static in vivo brain
      images have demonstrated that scatter correction significantly improves the
      accuracy of regional quantitation of single-photon emission tomography (SPET)
      brain images. Since the regional distribution of activity changes following a
      bolus injection of a typical neuroreceptor ligand, we examined the effect of
      scatter correction on the compartmental modeling of serial dynamic images of
      striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride.
      Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a
      study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and
      data acquisition over a period of 14 h. A transmission scan was obtained in each
      study for attenuation and scatter correction. Distribution volumes were
      calculated by means of compartmental nonlinear least-squares analysis using
      metabolite-corrected arterial input function and brain data processed with
      scatter correction using narrow-beam geometry micro (SC) and without scatter
      correction using broad-beam micro (NoSC). Effects of SC were markedly different
      among brain regions. SC increased activities in the putamen and thalamus after 1
      1.5 h while it decreased activity during the entire experiment in the temporal
      cortex and cerebellum. Compared with NoSC, SC significantly increased specific
      distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297).
      Compared with NoSC, SC made regional distribution of the specific distribution
      volume closer to that of [(18)F]fallypride. It is concluded that SC is required
      for accurate quantification of distribution volumes of receptor ligands in SPET
      studies.

PMID- 14730407
TI  - Exceptional increase in somatostatin receptor expression in pancreatic
      neuroendocrine tumour, visualised with (68)Ga-DOTATOC PET.

PMID- 14730408
TI  - Clinical cardiac PET in the future.

PMID- 14730409
TI  - Dominantly inherited progressive pseudorheumatoid dysplasia with hypoplastic
      toes.
AB  - OBJECTIVE: To present four related patients with progressive pseudorheumatoid
      dysplasia (PPsRD) each with distinctive history, unique phenotype and some
      peculiar radiographic findings. RESULTS AND CONCLUSIONS: The history was
      characterised by weather-dependent articular pain. The unique phenotypic features
      were hypoplasia/dysplasia of one or two toes. Peculiar radiographic findings were
      hypoplasia of the 3rd and 4th metatarsals, platyspondyly with rectangular shape
      of the lumbar spinal canal, progressive narrowing of the joint spaces and early
      synovial chondromatosis. Finally, the condition was inherited as a dominant
      trait. This constellation of abnormalities constitutes a distinct form of PPsRD.
      PPsRD must be differentiated from other bone dysplasias, specifically
      spondyloepiphyseal dysplasias, autosomal dominant spondylarthropathy, juvenile
      rheumatoid arthritis and osteoarthritis.

PMID- 14730410
TI  - Arabinoxylan and mono- and dimeric ferulic acid release from brewer's grain and
      wheat bran by feruloyl esterases and glycosyl hydrolases from Humicola insolens.
AB  - An enzyme preparation from the thermophilic fungus Humicola insolens, Ultraflo L,
      was able to solubilise more than half of the biomass of brewer's grain and wheat
      bran, two agro-industrial co-products. While almost all of the ferulic acid was
      released in the free form, the majority of diferulates were released still
      attached to soluble feruloylated oligosaccharides, except for the 8,5' benzofuran
      form, which remained mostly in the residue. H. insolens also produced an esterase
      capable of releasing over 50% of p-coumaric acid present in wheat bran, but only
      9% from the brewer's grain. The polysaccharide content in the residues after
      enzyme treatment comprised mostly cellulose and arabinoxylan, which suggests that
      part of the arabinoxylan in these residues is inaccessible to the xylanases of H.
      insolens. Differences in the solubilised arabinose-to-xylose ratio coupled to
      high free ferulate release suggest that the structure of feruloylated
      arabinoxylan in barley and wheat may differ.

PMID- 14730411
TI  - MRI of the posterior tectorial and atlanto-occipital membranes in the late stage
      of whiplash injury.

PMID- 14730412
TI  - Effect of the novel anxiolytic drug deramciclane on cytochrome P(450) 2D6
      activity as measured by desipramine pharmacokinetics.
AB  - BACKGROUND: In vitro findings have indicated that the novel anxiolytic drug,
      deramciclane, is an inhibitor of the cytochrome P(450) (CYP) 2D6 enzyme and co
      administration of deramciclane and the CYP2D6 probe drug desipramine is possible
      in clinical practice. OBJECTIVE: To evaluate the effects of deramciclane on
      CYP2D6 activity as measured by desipramine pharmacokinetics and pharmacodynamics
      using paroxetine as a positive control for CYP2D6 inhibition. METHODS: Fifteen
      healthy subjects received either 60 mg deramciclane, 20 mg paroxetine or matched
      placebo for 8 days in randomized order in this double-blind, cross-over study. On
      day 8 of each study phase, the subjects received a 100-mg single dose of
      desipramine. Desipramine and its CYP2D6-dependent metabolite, 2-OH-desipramine,
      concentrations were measured for 240 h. Measurement of secretion of saliva,
      Visual Analogue Scale assessment of dryness of mouth and tiredness were carried
      out on day 7 and day 8 to assess the pharmacodynamic consequences of deramciclane
      or paroxetine co-administration with desipramine. RESULTS: Repeated
      administration of deramciclane doubled the AUC of desipramine ( P<0.001), while
      paroxetine caused a 4.8-fold increase in the AUC of desipramine ( P<0.001).
      Significant correlations were observed with paroxetine (r(s)=0.84, P<0.001) and
      deramciclane (r(s)=0.51, P=0.0498) concentrations and the magnitude of increase
      of desipramine AUC. Both deramciclane and paroxetine decreased the formation of 2
      OH-desipramine in the first-pass phase. The AUC ratio of 2-OH
      desipramine/desipramine was decreased by 39% ( P<0.001) by deramciclane and by
      74% ( P<0.001) by paroxetine. There were no changes in the secretion of saliva
      during co-administration of desipramine with deramciclane compared with placebo.
      CONCLUSION: Although deramciclane seems to be a weaker inhibitor of CYP2D6 than
      paroxetine, dose adjustment of drugs metabolized by CYP2D6 may be needed when
      used concomitantly with deramciclane.

PMID- 14730413
TI  - EEG activity related to preparation and suppression of eye movements in three
      dimensional space.
AB  - Eight normal subjects made visually guided eye movements to four LED targets
      placed at two different distances (20 and 70 cm) and on either side (+/-10
      degrees ) at 70 cm. Four types of eye movements were elicited: pure saccades,
      convergence, divergence, and combined (divergent saccades). EEG activity was
      recorded from 62 electrodes and was aligned to stimulus onset. A negativity
      peaked after 140 ms and was modulated according to the location of the stimulus
      in space and the type of movement prepared, mainly in central and posterior
      cortex. For saccade targets, we confirmed a stimulus-related negativity in the
      posterior and central cortical area, contralateral to target direction. For
      convergence and divergence targets, this negativity was bilaterally distributed;
      convergence targets activated a rather extended cortical network in the central
      and posterior area, while divergence targets activated a more confined posterior
      area, spreading ventrally from the occipital cortex. Cortical activity for
      combined targets was lateralised contralaterally to stimulus direction but its
      topography resembled more closely that after the divergence stimulus. When
      observers suppressed the relevant eye movement to the stimulus, EEG activity was
      enhanced on the right hemisphere, showing the more pronounced effect on the right
      occipital-temporal and central-parietal electrode sites.

PMID- 14730416
TI  - Interaction between estrogens and antidepressants in the forced swimming test in
      rats.
AB  - RATIONALE: Several reports suggest that estrogens possess antidepressant effects
      and could facilitate the action of some antidepressants. OBJECTIVE: To analyze
      the interaction between three different types of estrogens, 17 beta-estradiol
      (E(2)), ethinylestradiol (EE(2)) or diethyl-stilbestrol (DES) and the
      antidepressants, fluoxetine (FLX) or desipramine (DMI) in ovariectomized female
      rats subjected to an animal model for the study of antidepressant compounds, the
      forced swimming test (FST). METHODS: The effect of the combination of a sub
      optimal dose of FLX (2.5 mg/kg) or DMI (2.5 mg/kg) with a sub-active dose of E(2
      )(10 microg/kg), EE(2), (2.5 or 5 microg/kg) or DES (1 mg/kg) was analyzed in
      both the FST and the open field paradigm. RESULTS: The combination of a sub
      optimal dose of E(2) or DES with that of the antidepressant DMI resulted in a
      clear antidepressant-like effect, evidenced by a significant decrease in
      immobility accompanied by an increase in climbing behavior. Sub-optimal doses of
      either E(2) or DES also facilitated the antidepressant-like effect of a sub
      optimal dose of FLX. In this case, a decrease in immobility with a concomitant
      increase in swimming behavior was observed. Finally, the combination of EE(2)
      with either DMI or FLX decreased immobility and induced an increase in both
      swimming and climbing behaviors. All combinations decreased rats' locomotor
      activity when evaluated in the open field test. CONCLUSION: In the FST estrogens
      were able to facilitate the action of two different kinds of antidepressants;
      however, these effects were dependent on the type of estrogen used.

PMID- 14730417
TI  - Comparative pharmacology of human beta-adrenergic receptor subtypes-
      characterization of stably transfected receptors in CHO cells.
AB  - Although many beta1-receptor antagonists and beta2-receptor agonists have been
      used in pharmacotherapy for many years their pharmacological properties at all
      three known subtypes of beta-adrenergic receptors are not always well
      characterized. The aim of this study was, therefore, to provide comparative
      binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol,
      fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and
      antagonists (propranolol, alprenolol, atenolol, metoprolol, bisoprolol,
      carvedilol, pindolol, BRL 37344, CGP 20712, SR 59230A, CGP 12177, ICI 118551) at
      all three subtypes of human beta-adrenergic receptors in an identical cellular
      background. We generated Chinese hamster ovary (CHO) cells stably expressing the
      three beta-adrenergic receptor subtypes at comparable levels. We characterized
      these receptor subtypes and analyzed the affinity of routinely used drugs as well
      as experimental compounds in competition binding studies, using the non-selective
      antagonist 125I-cyanopindolol as a radioligand. Furthermore, we analyzed the beta
      receptor-mediated adenylyl cyclase activity in isolated membranes from these cell
      lines. The results from our experiments show that all compounds exhibit distinct
      patterns of selectivity and activity at the three beta-receptor subtypes. In
      particular, a number of beta2- or beta3-receptor agonists that are inverse
      agonists at the other subtypes were identified. In addition, beta1-receptor
      antagonists with agonistic activity at beta2- and beta3-receptors were found.
      These specific mixtures of agonism, antagonism, and inverse agonism at different
      subtypes may have important implications for the therapeutic use of the
      respective compounds.

PMID- 14730418
TI  - Origin of ATP for Ca2+-induced contraction in the guinea-pig femoral artery.
AB  - Previously, we have described differences between the rat proximal colon and
      femoral artery with respect to the role of ATP newly synthesized by creatine
      kinase. In the present study the role of newly synthesized ATP was studied in the
      guinea-pig femoral artery to examine species differences. In the alpha-toxin
      permeabilized preparation of the guinea-pig femoral artery, the rapid Ca(2+)
      induced contraction was suppressed when creatine kinase activity was inhibited.
      The contraction was restored completely by treatment with NaN(3), an inhibitor of
      ecto-ATPase, the enzyme that breaks down exogenous ATP. Thus, ATP newly
      synthesized by creatine kinase may have no role in contraction of the guinea-pig
      femoral artery. This is in marked contrast to the rat femoral artery, in which
      Ca(2+)-induced contractions are almost completely inhibited by inhibition of
      creatine kinase activity but only partly restored by NaN(3). To characterize the
      difference between the guinea-pig and rat tissue, the origin of ATP required for
      contraction was determined in intact preparations. Monoiodoacetic acid, an
      inhibitor of glycolysis, inhibited the high K(+)-induced contraction in the
      guinea-pig femoral artery more potently than in the rat tissue. In contrast, an
      inhibitor of mitochondrial respiration, carbonylcyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP), inhibited contraction in femoral
      arteries from rats, but not from guinea-pigs. These results suggest that
      contraction in the rat femoral artery is dependent largely on oxidative
      phosphorylation, while contraction in the guinea-pig tissue is dependent only on
      glycolysis. Because oxidative phosphorylation generates ATP and phosphocreatine,
      while glycolysis generates only ATP, the strong dependence of the contraction of
      the rat femoral artery on the oxidative phosphorylation is consistent with its
      dependence on ATP newly synthesized by creatine kinase from ADP and
      phosphocreatine, as previously shown. Thus, it is proposed that ATP, newly
      synthesized by creatine kinase, in addition to ATP generated by oxidative
      phosphorylation, is utilized for contraction in the rat femoral artery, while
      glycolysis produces sufficient ATP for contraction in the guinea-pig femoral
      artery.

PMID- 14730419
TI  - Mass spectrometry proteomic analysis of stress adaptation reveals both common and
      distinct response pathways in Propionibacterium freudenreichii.
AB  - Microorganisms used in food technology and probiotics are exposed to
      technological and digestive stresses, respectively. Traditionally used as Swiss
      type cheese starters, propionibacteria also constitute promising human
      probiotics. Stress tolerance and cross-protection in Propionibacterium
      freudenreichii were thus examined after exposure to heat, acid, or bile salts
      stresses. Adapted cells demonstrated acquired homologous tolerance. Cross
      protection between bile salts and heat adaptation was demonstrated. By contrast,
      bile salts pretreatment sensitized cells to acid challenge and vice versa.
      Surprisingly, heat and acid responses did not present significant cross
      protection in P. freudenreichii. During adaptations, important changes in
      cellular protein synthesis were observed using two-dimensional electrophoresis.
      While global protein synthesis decreased, several proteins were overexpressed
      during stress adaptations. Thirty-four proteins were induced by acid
      pretreatment, 34 by bile salts pretreatment, and 26 by heat pretreatment. Six
      proteins are common to all stresses and represent general stress-response
      components. Among these polypeptides, general stress chaperones, and proteins
      involved in energetic metabolism, oxidative stress response, or SOS response were
      identified. These results bring new insight into the tolerance of P.
      freudenreichii to heat, acid, and bile salts, and should be taken into
      consideration in the development of probiotic preparations.

PMID- 14730420
TI  - Case-control study of risk factors for fractures of the distal radius and
      proximal humerus among the Japanese population.
AB  - We conducted a case-control study to identify risk factors for fractures of the
      distal radius and proximal humerus. Subjects were selected from women aged 45 and
      over with distal radius and proximal humerus fractures, resulting from minor
      trauma. Two age- and gender-matched controls for each case were selected from
      patients who subsequently visited the same clinic for treatment of conditions
      other than fractures. Questionnaires including anthropometric data, past and
      current physical activity, and lifestyle were sent by mail to both subjects and
      controls. A total of 140 women with distal radius fractures (mean age 67.4 years)
      and 242 controls were analyzed. Falls during the previous year were a significant
      risk factor, while futon use (instead of bed use) before fracture was a
      protective factor for distal radius fractures. A total of 37 women with proximal
      humerus fractures (mean age 76.3 years) and 67 controls were analyzed. Weight
      loss was a significant risk factor, while greater frequency of going outside
      significantly decreased the risk of proximal humerus fracture. There was no
      significant correlation with eating habits, milk and alcohol consumption, or
      smoking to the risk of either fracture.

PMID- 14730421
TI  - The validity of decision rules for selecting women with primary osteoporosis for
      bone mineral density testing.
AB  - The purpose of this study was to determine the validity of the Osteoporosis Risk
      Assessment Instrument (ORAI), Osteoporosis Self-Assessment Tool (OST) chart and
      equation, and a criterion based on body weight for identifying women with
      asymptomatic primary osteoporosis. Prospective recruitment and chart abstractions
      from family practices of three University affiliated hospitals were completed for
      women aged 45 years or more with baseline bone mineral density (BMD) testing
      results by dual energy X-ray absorptiometry. Those taking bone active medication
      other than hormone therapy, with prior fragility fracture or with risk factors
      for secondary osteoporosis were excluded. Women were categorized as being normal,
      osteopenic or osteoporotic by lowest BMD T-score at either the femoral neck or
      lumbar spine (L1-L4). Sensitivity, specificity and area under the receiver
      operating characteristic (ROC) curve to identify those with osteoporosis were
      determined for each decision rule. The positive predictive value (PPV) for
      detecting osteoporosis after using a second cut point to convert each decision
      rule into a risk index (low, moderate or high risk) was also determined. The
      sensitivity of the decision rules to identify women with osteoporosis ranged from
      92% to 95% and specificity from 35% to 46%. The area under the ROC curves were
      significantly better for the ORAI (0.80), OST chart (0.82) and OST equation
      (0.82) compared with the body weight criterion (0.73). PPV for detecting
      osteoporosis ranged from 30% to 58% among women deemed at high risk. These data
      confirm the validity of the ORAI, the OST chart and the OST equation as screening
      tools for BMD testing. Further evidence is required to confirm the validity of
      the body weight criterion.

PMID- 14730422
TI  - Consequences of hip fracture on activities of daily life and residential needs.
AB  - The aim of this study was to describe the consequences of hip fracture with
      respect to changes in residential needs and the ability to perform activities of
      daily life. Patients 50 years and older admitted to the two largest hospitals of
      Oslo with a hip fracture during the period May 1996 through April 1997 were
      identified. In November 1997 a questionnaire on residential needs, activities of
      daily life, hip pain and health status was sent to the patients still alive (n =
      767). After reminders, the questionnaires of 593 patients (77%) were included.
      Logistic regression analysis was applied to assess items associated with
      functional limitation and need for residential care. The proportion of patients
      living in nursing homes increased from 15% before to 30% after the hip fracture,
      and men were twice as likely to move into a nursing home than women. Of the
      patients living in their own homes before the hip fracture, 6% of those < 75
      years compared with 33% of those > 85 years had to move to nursing home after hip
      fracture. The proportion of patients walking without any aid decreased from 76 to
      36%, and 43% of the patients lost their prefracture ability to move outside on
      their own. More than a fourth of the patients (28%) lost their ability to cook
      their own dinner after sustaining hip fracture. The probability of these events
      increased with increasing age. The probability of reporting inferior health
      status and for having hip pain that affected sleep after the fracture was
      unrelated to age. Many patients sustaining a hip fracture, and in particular the
      oldest patients, have reduced ability to perform activities of daily life.

PMID- 14730423
TI  - Structures of oligosaccharides derived from Cladosiphon okamuranus fucoidan by
      digestion with marine bacterial enzymes.
AB  - A fucoidan-utilizing marine bacterium, Fucophilus fucoidanolyticus, was
      cultivated in medium containing fucoidan from Cladosiphon okamuranus. The C.
      okamuranus fucoidan was digested into oligosaccharides with the intracellular
      enzymes of F. fucoidanolyticus, and their structures were determined by nuclear
      magnetic resonance analyses. Some of their structures are represented by one
      general structural formula, (-3 L-Fuc palpha1-3 L-Fuc p(4- O-sulfate)alpha1-3 L
      Fuc p(4- O-sulfate)alpha1-3( D-Glc pUAalpha1-2) L-Fuc palpha1)(m)-3 L-Fuc palpha1
      3 L-Fuc p(4- O-sulfate)alpha1-3 L-Fuc p(4- O-sulfate) alpha1-3 L-Fuc p ( m = 0,
      1, 2, or 3). We concluded that all oligosaccharides obtained were derived from a
      sulfated-fucose-containing polysaccharide of C. okamuranus, which has a repeating
      unit of (-3 L-Fuc palpha1-3 L-Fuc p(4- O-sulfate)alpha1-3 L-Fuc p(4- O
      sulfate)alpha1-3( D-Glc pUAalpha1-2) L-Fuc palpha1-).

PMID- 14730424
TI  - PCR-based ribosomal DNA detection technique for microalga (Heterosigma carterae)
      causing red tide and its application to a biosensor using labeled probe.
AB  - A technique for detecting Raphidophycean, a bloom-forming genus of algae, was
      developed using a specific DNA probe. The design of the probe was based on a
      sequence polymorphism within the small subunit (SSU) ribosomal RNA gene (rDNA) of
      this strain by using fluorescence polarization (FP) analysis and the BIAcore 2000
      biosensor, which utilized surface plasmon resonance (SPR). The specific sequence
      in SSU rDNA for Heterosigma carterae was determined by sequence data analysis.
      One pair of polymerase chain reaction (PCR) probes was designed for use in making
      the identification. H. carterae SSU rDNA was amplified by PCR. Using a
      fluoroscein isothiocyanate-labeled or biotin-labeled oligonucleotide probe, the
      PCR-amplified rDNA was selectively detected as an FP-intensity change via FP
      analysis or as a resonance-unit change via SPR. Although total time for final
      detection after sampling was within 3 hours, specific rDNA could be detected
      within 10 minutes after PCR through these detection methods.

PMID- 14730425
TI  - Antimicrobial activities and matrix-assisted laser desorption/ionization mass
      spectrometry of Bacillus isolates from the marine sponge Aplysina aerophoba.
AB  - The aim of this study was to isolate bacteria that are resistant to the strong
      antimicrobial metabolites characteristic of Aplysina aerophoba. For this purpose,
      bacterial isolation was performed on agar plates to which sponge tissue extract
      had been added. Following screening for antifungal and antimicrobial activities,
      5 strains were chosen for more detailed analyses. 16S ribosomal DNA sequencing
      revealed that all isolates belonged to the genus Bacillus, specifically B.
      subtilis and B. pumilus. Using a combination of matrix-assisted laser desorption/
      ionization mass spectrometry typing of whole cells and antimicrobial bioassays
      against selected reference strains, the bioactive metabolites were identified as
      lipopeptides.

PMID- 14730426
TI  - Virus-like particles suppress growth of the red-tide-forming marine
      dinoflagellate Gymnodinium mikimotoi.
AB  - We isolated 2 virus-like agents that suppressed growth of Gymnodinium mikimotoi
      from coastal waters of the Uwa Sea, Japan. The agents found in the flagellate
      cells, named GM6 and GM7, were filterable in a 0.22-microm-pore filter with
      approximately 100-nm shapes. Electron microscopic observation showed the presence
      of virus-like particles in severely damaged G. mikimotoi cells infected by GM6.
      The growth-suppression activity of the agents (GM6 or GM7) was lost by heating at
      50 degrees C, with treatments of DNase and protease, and filtration through a
      0.05-microm filter. Our results suggest that the agents are DNA viruses
      infectious to and virulent for G. mikimotoi. This is the first report of a virus
      like agent specific to G. mikimotoi.

PMID- 14730427
TI  - Sponge-cell culture? A molecular identification method for sponge cells.
AB  - Dissociated sponge cells are easily confused with unicellular organisms. This has
      been an obstacle in the development of sponge-cell lines. We developed a
      molecular detection method to identify cells of the sponge Dysidea avara in
      dissociated cell cultures. The 18S ribosomal RNA gene from a Dysidea avara
      specimen was sequenced and compared to eukaryotic 18S rDNA sequences picked up
      from a proliferating cell culture that originated from a dissociated Dysidea
      avara specimen. Our method proved unambiguously that this was not a sponge-cell
      culture. Therefore, it provides a valuable tool for further research on sponge
      cell cultures.

PMID- 14730428
TI  - Grouping newly isolated docosahexaenoic acid-producing thraustochytrids based on
      their polyunsaturated fatty acid profiles and comparative analysis of 18S rRNA
      genes.
AB  - Seven strains of marine microbes producing a significant amount of
      docosahexaenoic acid (DHA; C22:6, n-3) were screened from seawater collected in
      coastal areas of Japan and Fiji. They accumulate their respective intermediate
      fatty acids in addition to DHA. There are 5 kinds of polyunsaturated fatty acid
      (PUFA) profiles which can be described as (1) DHA/docosapentaenoic acid (DPA;
      C22:5, n-6), (2) DHA/DPA/eicosapentaenoic acid (EPA; C20:5, n-3), (3) DHA/EPA,
      (4) DHA/DPA/EPA/arachidonic acid (AA; C20:4, n-6), and (5)
      DHA/DPA/EPA/AA/docosatetraenoic acid (C22:4, n-6). These isolates are proved to
      be new thraustochytrids by their specific insertion sequences in the 18S rRNA
      genes. The phylogenetic tree constructed by molecular analysis of 18S rRNA genes
      from the isolates and typical thraustochytrids shows that strains with the same
      PUFA profile form each monophyletic cluster. These results suggest that the C20
      22 PUFA profile may be applicable as an effective characteristic for grouping
      thraustochytrids.

PMID- 14730430
TI  - Development of mitochondrial DNA primers for use with homarid lobsters.
AB  - DNA primer sets were developed for the amplification of complete mitochondrial
      genomes for both European and American lobsters in 4 suitable-sized segments.
      Optimal conditions for polymerase chain reaction routine screening were
      established. The 4 segments were screened with 24 restriction endonucleases in a
      test population sample, covering the whole distribution of the European lobster,
      and restriction patterns of each enzyme were revealed. A segment of 3000 bp
      comprising part of cytochrome oxidase I gene, the genes cytochrome oxidase II and
      III, subunits 6 and 8 of ATPase, subunit 3 of the NAD dehydrogenase, and various
      transfer RNAs, was found to be the most polymorphic. A number of enzyme patterns
      in each segment differentiated European and American lobsters. Extra bands were
      observed, indicating heteroplasmy phenomena, which were verified with various
      approaches. Furthermore, a primer set that enables 1-step ampli fication of the
      complete mitochondrial genome of the European lobster was established.

PMID- 14730429
TI  - Phylogenetic diversity of dissimilatory sulfite reductase genes from deep-sea
      cold seep sediment.
AB  - The phylogenetic diversity of dissimilatory sulfite reductase (DSR, EC 1.8.99.3)
      alpha-subunit genes from a deep-sea cold seep was analyzed. Bulk genomic DNA was
      extracted from the cold seep sediment and used for amplification by polymerase
      chain reaction (PCR) of DSR alpha-subunit gene. Two sizes of PCR products, 1.4 kb
      (expected) and 1.3 kb (unexpected), were amplified. Sixteen clones of the 1.4-kb
      amplicons and 16 clones of 1.3-kb amplicons, a total of 32 clones, were obtained
      and grouped into operational DSR units (ODUs) based on restriction fragment
      length polymorphism (RFLP) by digestion with HaeIII and MboI. A total of 14 ODUs,
      i.e., 5 ODUs from 1.4-kb amplicon clones and 9 ODUs from 1.3-kb amplicon clones,
      were recovered. About 400 bp of the 5' ends of all the clones was sequenced and
      validated the RFLP-based ODU grouping. All the 5'-end 400-bp sequences of ODUs,
      even from the 1.3-kb amplicons, showed the characteristic DSR amino acid sequence
      motifs. The ODUs from 1.4-kb amplicons were closely related to the delta
      Proteobacterial lineage with the DSR genes from epsilon-Proteobacterial epibionts
      of the hot vent worm Alvinella pompejana. The ODUs from 1.3-kb amplicons were
      mostly related to the unknown but possibly archaeal lineage. The diversity of the
      DSR genes may indicate the diversity of sulfate reducers in the seep sediment as
      well as the complexity of electron donors including methane.

PMID- 14730431
TI  - Potential of thraustochytrids to partially replace fish oil in Atlantic salmon
      feeds.
AB  - The replacement of fish oil with a dried product made from thraustochytrid
      culture, a marine microorganism, in canola-oil-based diets for Atlantic salmon
      was investigated. Salmon (37 g) were fed for 51 days on diets containing only
      canola oil, canola oil and fish oil, or canola oil and the thraustochytrid. There
      were no significant differences in final weight (106.1 +/- 1.1 g), weight gain
      (69.6 +/- 1.1 g), feed consumption (16.5 +/- 0.2 mg dry matter g(-1) d(-1)), feed
      efficiency ratio (1.15 +/- 0.03 g (g-1)), or productive protein value (51.2% +/-
      1.7%) between the diets. Nor were there any significant differences in whole-body
      chemical composition, organ somatic indices, or measures of immune function.
      However, following transfer to seawater and 2 challenges with Vibrio anguillarum,
      cumulative mortality was significantly lower in fish fed some fish oil than in
      those fed the 2 diets containing no fish oil. In conclusion, the thraustochytrid
      had no detrimental effects on the performance of salmon but, at the current
      inclusion of 10%, failed to confer the same effect as fish oil under challenging
      conditions.

PMID- 14730432
TI  - Genetic identification and phylogeny of three species of the genus Trachurus
      based on mitochondrial DNA analysis.
AB  - The genetic identification and the phylogenetic relationships of 3 European
      species of the genus Trachurus (T. trachurus, T. mediterraneus, and T.
      picturatus) across their geographical distribution, have been investigated by
      mitochondrial DNA analysis. Both cytochrome b and 16S ribosomal DNA sequence
      analysis revealed the existence of several species-specific positions that
      distinguish the 3 studied species. Genetic distances between the species
      indicated that T. mediterraneus and T. picturatus are more closely related than
      T. trachurus. Similar topologies have been produced by neighbor-joining, maximum
      likelihood, and maximum-parsimony trees, and they were in accordance with
      previous taxonomic classification. Internucleotide and intranucleotide diversity
      of T. picturatus was 2 times higher than that of T. mediterraneus and T.
      trachurus, possibly owing to the low levels of fishing pressure for T.
      picturatus. This is the first report of the phylogenetic relationships of the 3
      Trachurus species and provides a possible scenario of the time of divergence
      related to the closure of the Gibraltar Straits. In addition, the present results
      can be used for genetic identification of the 3 species, even from the early
      stage of eggs, and for detection of commercial fraud.

PMID- 14730433
TI  - The chimeric CYP21P/CYP21 gene and 21-hydroxylase deficiency.
AB  - The chimeric CYP21P/CYP21 gene is a consequence of a 26- or 32-kb deletion in the
      C4-CYP21 repeat module of CYP21P, tenascin A ( XA), serine/threonine nuclear
      protein kinase ( RP2), and the C4B and CYP21 genes in congenital adrenal
      hyperplasia (CAH) with steroid 21-hydroxylase deficiency. To date, there have
      been three distinct chimeras found in CAH patients in ethnic Chinese. Initiation
      for production of these molecules is proposed to be chi-like sequences and a
      minisatellite consensus existing in several noncoding regions in CYP21 genes.
      These molecules have the 5' end of the CYP21P-specific sequence in common but
      differ in the 3' end of CYP21-specific genes. In addition, there appears to be a
      3.2-kb fragment generated by Taq I digestion, which leads to allele dropout in
      PCR amplification for detecting the aberrant splicing site of the IVS2 -12A/C>G
      mutation at nucleotide (nt) 655 in the CYP21 gene. Therefore, the chimeric
      CYP21P/CYP21 cannot be detected by conventional methods. It has been demonstrated
      that a PCR product amplified with allele-specific primers covering tenascin B (
      TNXB) to the 5' end of the CYP21 gene combined with Southern analysis by Ase I
      and Nde I digestion may be used for identifying the chimera in the CYP21 gene.

PMID- 14730434
TI  - Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and
      clinical features in Japan.
AB  - The mitochondrial DNA (mtDNA) G13513A mutation in the ND5 subunit gene has been
      recently reported as a common cause of some phenotypes of mitochondrial myopathy.
      Until now, the prevalence and characteristics of this mutation in Leigh syndrome
      (LS) has not been determined. We screened 84 patients with Leigh syndrome (LS)
      and found the mutation in six (7%) of them. The proportions of mutant mtDNA in
      muscles were relatively low (42-70%). The onset of symptoms for patients with
      this mutation was from 9 months to 5 years. It should be noted that five patients
      had cardiac conduction abnormalities, particularly Wolff-Parkinson-White (WPW)
      syndrome (three patients). This study suggests that G13513A mutation is a
      frequent cause of LS and that patients with this mutation may have a
      characteristic clinical course.

PMID- 14730435
TI  - Autonomic nervous system appears to play a role in obliteration of processus
      vaginalis.
AB  - BACKGROUND: Failed obliteration of processus vaginalis (PV) has recently been
      proposed to be due to persistence of the smooth muscle (SM), which is transiently
      present to generate the physical force to descend the testis. Sacs from hernia,
      hydrocele, or undescended testis reveal alterations in Ca(2+) contents. Since
      Ca(2+) signaling and some regulatory proteins are involved in programmed cell
      death (PCD), a flow cytometric evaluation was planned to evaluate the expression
      of inducers or inhibitors of PCD in sacs from different diagnostic sources.
      METHODS: Sacs associated with male hernia ( n=16), female hernia ( n=11),
      undescended testis ( n=9), and hydrocele ( n=11) were evaluated for binding of
      annexin and expressions of Bcl-2, Bax, Fas, Fas-ligand (Fas-L), and Fas+Fas-L.
      The binding and expressions in cells that express alpha-smooth muscle actin
      (alpha-SMA) were also determined. Expressions according to the groups were
      compared through unpaired t-test, and P values less than 0.05 were considered to
      be significant. RESULTS: Sacs associated with undescended testis that contain the
      least SM revealed the most annexin binding, and sacs associated with hernia that
      contain the most SM binded the least annexin. However, expressions of Bcl-2, Bax,
      Fas, Fas-L and Fas+Fas-L have not revealed a significant difference. On the other
      hand, Bax and Fas expressions of cells that express alpha-SMA have been
      significantly higher in sacs associated with undescended testis. CONCLUSIONS:
      Since increase of Bax and Fas in cells that express alpha-SMA are encountered in
      sacs with the least SM content, Bax and Fas appear to play roles in the amount of
      persisting SM. The necessities of initial depletion of Ca(2+) stores through
      inositol 1,4,5-trisphosphate receptors and subsequent increase of Bax and Fas
      levels in the mitochondrial pathway of PCD, together with the role of the
      sympathetic system in maintenance of SM, suggest a determinative role of the
      autonomic nervous system for obliteration of PV.

PMID- 14730436
TI  - Polypropylene mesh use in the prevention of incisional hernia.

PMID- 14730437
TI  - Biomechanical simulations of the spine deformation process in adolescent
      idiopathic scoliosis from different pathogenesis hypotheses.
AB  - It is generally recognized that progressive adolescent idiopathic scoliosis (AIS)
      evolves within a self-sustaining biomechanical process involving asymmetrical
      growth modulation of vertebrae due to altered spinal load distribution. A
      biomechanical finite element model of normal thoracic and lumbar spine
      integrating vertebral growth was used to simulate the progression of spinal
      deformities over 24 months. Five pathogenesis hypotheses of AIS were represented,
      using an initial geometrical eccentricity (gravity line imbalance of 3 mm or 2
      degrees rotation) at the thoracic apex to trigger the self-sustaining deformation
      process. For each simulation, regional (thoracic Cobb angle, kyphosis) and local
      scoliotic descriptors (axial rotation and wedging of the thoracic apical
      vertebra) were evaluated at each growth cycle. The simulated AIS pathogeneses
      resulted in the development of different scoliotic deformities. Imbalance of 3 mm
      in the frontal plane, combined or not with the sagittal plane, resulted in the
      closest representation of typical scoliotic deformities, with the thoracic Cobb
      angle progressing up to 39 degrees (26 degrees when a sagittal offset was added).
      The apical vertebral rotation increased by 7 degrees towards the convexity of the
      curve, while the apical wedging increased to 8.5 degrees (7.3 degrees with the
      sagittal eccentricity) and this deformity evolved towards the vertebral frontal
      plane. A sole eccentricity in the sagittal plane generated a non-significant
      frontal plane deformity. Simulations involving an initial rotational shift (2
      degrees ) in the transverse plane globally produced relatively small and non
      typical scoliotic deformations. Overall, the thoracic segment predominantly was
      sensitive to imbalances in the frontal plane, although unidirectional geometrical
      eccentricities in different planes produced three-dimensional deformities at the
      regional and vertebral levels, and their deformities did not cumulate when
      combined. These results support the hypothesis of a prime lesion involving the
      precarious balance in the frontal plane, which could concomitantly be associated
      with a hypokyphotic component. They also suggest that coupling mechanisms are
      involved in the deformation process.

PMID- 14730439
TI  - Variation of endplate thickness in the cervical spine.
AB  - The purpose of the study was to investigate possible variation of thickness of
      the cervical spine endplate with respect to endplate orientation (superior or
      inferior endplate) and level distribution (C4-C7). Six human cervical spine
      segments C4-C7 were used to create six specimen of C4, C5, C6, and C7,
      respectively. The bony endplates of each vertebra were cleaned carefully from
      disc tissue without damaging the endplates. Six endplates with severe
      degenerative changes were excluded from the study. The posterior elements were
      removed, and a midaxial cut using a bone saw was performed through each vertebral
      body, thus producing a superior and inferior half. Each half-vertebra was then
      glued onto a piece of wood with the endplate oriented upwards and horizontally.
      For each specimen, four computed tomography scans were taken and thickness of the
      endplate was measured at five points on each scan perpendicular to the midaxial
      cut. Factorial analysis of variance (ANOVA) and Scheffe-test were used to detect
      significant differences. All peripheral regions were significantly thicker than
      the central point of the endplate if all measuring points were considered for
      statistical analysis, regardless of scan, endplate orientation or level (Scheffe
      test, P<0.001). In both superior and inferior endplates, peripheral areas were
      thicker than the central region (Scheffe-test, P<0.001). For all levels, the
      endplate within the peripheral regions was thicker than within the central region
      and the difference reached significance for the superior and inferior endplate of
      C4, C5, and C6 and the inferior endplate of C7 (Scheffe-test, P<0.05). The
      peripheral regions of the cervical spine endplate are usually thicker than its
      central region, regardless of endplate orientation and level (C4, C5, C6, C7)
      distribution.

PMID- 14730438
TI  - Anterior lumbar interbody fusion with carbon fiber cage loaded with bioceramics
      and platelet-rich plasma. An experimental study on pigs.
AB  - Platelet-rich plasma (PRP) is an autogenous source of growth factor and has been
      shown to enhance bone healing both in clinical and experimental studies. PRP in
      combination with porous hydroxyapatite has been shown to increase the bone
      ingrowth in a bone chamber rat model. The present study investigated whether the
      combination of beta tricalcium phosphate (beta-TCP) and PRP may enhance spinal
      fusion in a controlled animal study. Ten Danish Landrace pigs were used as a
      spinal fusion model. Immediately prior to the surgery, 55 ml blood was collected
      from each pig for processing PRP. Three-level anterior lumbar interbody fusion
      was performed with carbon fiber cages and staples on each pig. Autogenous bone
      graft, beta-TCP, and beta-TCP loaded with PRP were randomly assigned to each
      level. Pigs were killed at the end of the third month. Fusion was evaluated by
      radiographs, CT scanning, and histomorphometric analysis. All ten pigs survived
      the surgery. Platelet concentration increased 4.4-fold after processing.
      Radiograph examination showed 70% (7/10) fusion rate in the autograft level. All
      the levels with beta-TCP+PRP showed partial fusion, while beta-TCP alone levels
      had six partial fusions and four non-fusions ( P=0.08). CT evaluation of fusion
      rate demonstrated fusion in 50% (5/10) of the autograft levels. Only partial
      fusion was seen at beta-TCP levels and beta-TCP+PRP levels. Histomorphometric
      evaluation found no difference between beta-TCP and beta-TCP+PRP levels on new
      bone volume, remaining beta-TCP particles, and bone marrow and fibrous tissue
      volume, while the same parameters differ significantly when compared with
      autogenous bone graft levels. We concluded from our results in pigs that the PRP
      of the concentration we used did not improve the bone-forming capacity of beta
      TCP biomaterial in anterior spine fusion. Both beta-TCP and beta-TCP+PRP had
      poorer radiological and histological outcomes than that of autograft after 3
      months.

PMID- 14730441
TI  - Damage-based finite-element vertebroplasty simulations.
AB  - The objectives of this study were to quantify the efficacy of vertebroplasty
      according to: (1) damage and (2) cement quantity (fill) and modulus. Vertebral
      body damage was numerically simulated using a previously validated two
      dimensional finite-element model coupled with an elasto-plastic modulus reduction
      (EPMR) scheme. The effects of cement fill (% marrow replaced by cement, % MRC)
      and cement modulus on vertebral apparent modulus and trabecular bone tissue
      stress concentrations were parametrically assessed for four EPMR damage models
      (19%, 33%, 60%, and 91% modulus reduction). For this analysis, the elastic
      modulus of the trabecular bone tissue and marrow elements were assumed to be 10
      GPa and 10 kPa, respectively. The effect of cement modulus (varied in the range 1
      GPa to 9 GPa) on vertebral apparent modulus was also examined for partial fill
      (39% MRC) and complete fill (100% MRC) using the 33% modulus reduction damage
      model. In the case of polymethylmethacrylate (PMMA cement modulus = 2.16 GPa),
      restoration of the thoracic vertebral body (T10) apparent modulus to undamaged
      levels required 71% and 100% cement fill for the 19-33% and 60-91% modulus
      reduction damage models, respectively. Variations in cement modulus had no
      appreciable effect on the recovery of vertebral apparent modulus to undamaged
      levels for simulations of partial cement fill (39% MRC). For complete cement
      fill, however, a PMMA cement modulus produced approximately a 2-fold increase
      (82%) in vertebral apparent modulus relative to the undamaged vertebral body.
      Increasing the cement modulus to 9 GPa increased the vertebral apparent modulus
      over 2.5-fold (158%) relative to the undamaged state. The EPMR damage scheme and
      repair simulations performed in this study will help clinicians and cement
      manufacturers to improve vertebroplasty procedures.

PMID- 14730442
TI  - Turnover of carbon isotopes in tail hair and breath CO2 of horses fed an
      isotopically varied diet.
AB  - Temporal stable isotope records derived from animal tissues are increasingly
      studied to determine dietary and climatic histories. Despite this, the turnover
      times governing rates of isotope equilibration in specific tissues following a
      dietary isotope change are poorly known. The dietary isotope changes recorded in
      the hair and blood bicarbonate of two adult horses in this study are found to be
      successfully described by a model having three exponential isotope pools. For
      horse tail hair, the carbon isotope response observed following a dietary change
      from a C3 to a C4 grass was consistent with a pool having a very fast turnover
      rate ( t1/2 approximately 0.5 days) that made up approximately 41% of the isotope
      signal, a pool with an intermediate turnover rate ( t1/2 approximately 4 days)
      that comprised approximately 15% of the isotope signal, and a pool with very slow
      turnover rate ( t1/2 approximately 140 days) that made up approximately 44% of
      the total isotope signal. The carbon isotope signature of horse blood
      bicarbonate, in contrast, had a different isotopic composition, with
      approximately 67% of the isotope signal coming from a fast turnover pool ( t1/2
      0.2 days), approximately 17% from a pool with an intermediate turnover rate (
      t1/2 approximately 3 days) and approximately 16% from a pool with a slow turnover
      rate ( t1/2 approximately 50 days). The constituent isotope pools probably
      correspond to one exogenous and two endogenous sources. The exogenous source
      equates to our fast turnover pool, and the pools with intermediate and slow
      turnover rates are thought to derive from the turnover of metabolically active
      tissues and relatively inactive tissues within the body, respectively. It seems
      that a greater proportion of the amino acids available for hair synthesis come
      from endogenous sources compared to the compounds undergoing cellular catabolism
      in the body. Consequently, the isotope composition of blood bicarbonate appears
      to be much more responsive to dietary isotope changes, whereas the amino acids in
      the blood exhibit considerable isotopic inertia.

PMID- 14730443
TI  - Variation in predation risk and vole feeding behaviour: a field test of the risk
      allocation hypothesis.
AB  - Many prey animals experience temporal variation in the risk of predation and
      therefore face the problem of allocating their time between antipredator efforts
      and other activities like feeding and breeding. We investigated time allocation
      of prey animals that balanced predation risk and feeding opportunities. The
      predation risk allocation hypothesis predicts that animals should forage more in
      low- than in high-risk situations and that this difference should increase with
      an increasing attack ratio (i.e. difference between low- and high-risk
      situations) and proportion of time spent at high risk. To test these predictions
      we conducted a field test using bank voles ( Clethrionomys glareolus) as a prey
      and the least weasel ( Mustela nivalis nivalis) as a predator. The temporal
      pattern and intensity of predation risk were manipulated in large outdoor
      enclosures and the foraging effort and patch use of voles were measured by
      recording giving-up densities. We did not observe any variation in feeding effort
      due to changes in the level of risk or the proportion of time spent under high
      risk conditions. The only significant effect was found when the attack ratio was
      altered: the foraging effort of voles was higher in the treatment with a low
      attack ratio than in the treatment with a high attack ratio. Thus the results did
      not support the predation risk allocation hypothesis and we question the
      applicability of the hypothesis to our study system. We argue that the deviation
      between the observed pattern of feeding behaviour of bank voles and that
      predicted by the predation risk allocation hypothesis was mostly due to the
      inability of voles to accurately assess the changes in the level of risk.
      However, we also emphasise the difficulties of testing hypotheses under outdoor
      conditions and with mammals capable of flexible behavioural patterns.

PMID- 14730444
TI  - Genome-wide analysis of defense-responsive genes in bacterial blight resistance
      of rice mediated by the recessive R gene xa13.
AB  - Defense responses triggered by dominant and recessive disease resistance (R)
      genes are presumed to be regulated by different molecular mechanisms. In order to
      characterize the genes activated in defense responses against bacterial blight
      mediated by the recessive R gene xa13, two pathogen-induced subtraction cDNA
      libraries were constructed using the resistant rice line IRBB13--which carries
      xa13--and its susceptible, near-isogenic, parental line IR24. Clustering analysis
      of expressed sequence tags (ESTs) identified 702 unique expressed sequences as
      being involved in the defense responses triggered by xa13; 16% of these are new
      rice ESTs. These sequences define 702 genes, putatively encoding a wide range of
      products, including defense-responsive genes commonly involved in different host
      pathogen interactions, genes that have not previously been reported to be
      associated with pathogen-induced defense responses, and genes (38%) with no
      homology to previously described functional genes. In addition, R-like genes
      putatively encoding nucleotide-binding site/leucine rich repeat (NBS-LRR) and LRR
      receptor kinase proteins were observed to be induced in the disease resistance
      activated by xa13. A total of 568 defense-responsive ESTs were mapped to 588 loci
      on the rice molecular linkage map through bioinformatic analysis. About 48% of
      the mapped ESTs co-localized with quantitative trait loci (QTLs) for resistance
      to various rice diseases, including bacterial blight, rice blast, sheath blight
      and yellow mottle virus. Furthermore, some defense-responsive sequences were
      conserved at similar locations on different chromosomes. These results reveal the
      complexity of xa13-mediated resistance. The information obtained in this study
      provides a large source of candidate genes for understanding the molecular bases
      of defense responses activated by recessive R genes and of quantitative disease
      resistance.

PMID- 14730445
TI  - The transcription factor HACA mediates the unfolded protein response in
      Aspergillus niger, and up-regulates its own transcription.
AB  - The unfolded protein response (UPR) involves a complex signalling pathway in
      which the transcription factor HACA plays a central role. Here we report the
      cloning and characterisation of the hacA gene and its product from Aspergillus
      niger. ER (endoplasmic reticulum) stress results in the splicing of an
      unconventional 20-nt intron from the A. niger hacA mRNA, and is associated with
      truncation of the 5'-end of the hacA mRNA by 230 nt. In this study the UPR was
      triggered by over expressing tissue plasminogen activator (t-PA), and by
      treatment of mycelia with dithiothreitol (DTT) or tunicamycin. Overexpression of
      the processed form of hacA not only led to the up-regulation of bipA, cypB and
      pdiA--mimicking the UPR--but also led to the up-regulation of the hacA gene
      itself. In vitro binding assays confirmed that the HACA protein binds to the
      promoters of genes encoding ER-localised chaperones and foldases, and to the
      promoter of the hacA gene itself. Finally, a GFP-HACA fusion was shown to
      localise in the nucleus.

PMID- 14730446
TI  - Decreasing incidence of neonatal nosocomial bloodstream infections in a neonatal
      intensive care unit: antenatal corticosteroid treatment an innocent bystander?
AB  - We studied the effect of the use of antenatal steroid treatment on the incidence
      of nosocomial bloodstream infections (NBSI). All episodes of culture proven NBSI
      occurring after 96 h of hospitalisation were identified retrospectively during a
      10-year period (1991-2001). Throughout the study period, the use of antenatal
      steroids, demographic characteristics and morbidity of the patients were recorded
      prospectively. Since 1996 more efforts were made to use antenatal steroids to
      decrease neonatal morbidity and mortality. The incidence rates of NBSI were
      compared between period 1 (1991-1995) and period 2 (1996-2001). The overall
      incidence rate of NBSI dropped significantly from 7.4% (6.1%-8.9%) in period 1 to
      5.0% (4.0%-6.2%) in period 2 and was most pronounced in the birth weight category
      1000 g-1500 g (11.7%, 7.9%-15.0% to 6.9%, 4.3%-10.5%) and 1500 g-2500 g (3.6%,
      2.2%-5.6% to 1.4%, 0.6%-2.8%). Antenatal use of steroids increased overall from
      19% in 1991 to 51% in 2001 ( P<0.001). Since 1996 there was a decreasing number
      of ventilation days ( P=0.011) and decreasing incidence of patent ductus
      arteriosus ( P=0.001), while the incidence of neonatal surgery, chronic lung
      disease and duration of hospitalisation remained constant over time. CONCLUSION:
      increased use of antenatal steroids is associated with a decreasing incidence
      rate of nosocomial bloodstream infections in neonates with birth weights between
      1000 g and 2500 g, probably by decreasing the incidence of patent ductus
      arteriosus and/or due to improved respiratory outcome. This finding needs to be
      confirmed by randomised control trials or by a large prospective cohort study in
      similar population groups.

PMID- 14730447
TI  - Alternative morphs and plasticity of vulval development in a rhabditid nematode
      species.
AB  - The nematode species Rhabditis sp. SB347 (Family Rhabditidae) in standard culture
      conditions displays two developmental morphs with distinct modes of sexual
      reproduction: (1). females and males that develop through four feeding juvenile
      ("larval") stages; (2). self-fertile protandric hermaphrodites that develop
      through an obligatory non-feeding third juvenile stage, the "dauer" larva. In
      females and males, somatic gonad development begins in the first larval stage,
      whereas in hermaphrodites it is delayed to the second larval stage. Vulval
      development also differs between females and hermaphrodites: (1). the P8.p cell
      divides in females but stays undivided in hermaphrodites; (2). the number,
      timing, and source of inductive signals from the gonad to the vulval precursor
      cells differ between the two morphs. These results show that discrete vulva
      developmental routes can be adopted by animals of the same genotype.

PMID- 14730448
TI  - sll1722, an unassigned open reading frame of Synechocystis PCC 6803, codes for L
      myo-inositol 1-phosphate synthase.
AB  - L-myo-inositol 1-phosphate synthase (EC 5.5.1.4; MIPS) catalyzes conversion of
      glucose 6-phosphate to L-myo-inositol 1-phosphate, the first and the rate
      limiting step in the production of inositol, and has been reported from
      evolutionarily diverse organisms. Two forms of the enzyme have been characterized
      from higher plants, viz. cytosolic and chloroplastic, and the presence of MIPS
      has been earlier reported from the cyanobacteria (e.g. Spirulina sp.), the
      presumed chloroplast progenitors. The present study demonstrates possible
      multiple forms of MIPS and identifies the gene for one of them in the
      cyanobacterium Synechocystis sp. PCC 6803. Following detection of at least two
      immunologically cross-reactive MIPS forms, we have been able to identify from the
      fully sequenced Synechocystis genome an as yet unassigned open reading frame
      (ORF), sll1722, coding for the approx. 50-kDa MIPS protein, by using biochemical,
      molecular and bioinformatics tools. The DNA fragment corresponding to sll1722 was
      PCR-amplified and functional identity of the gene was confirmed by a
      complementation assay in Saccharomyces cerevisiae mutants containing a disrupted
      INO1 gene for the yeast MIPS. The sll1722 PCR product was cloned in Escherichia
      coli expression vector pET20b and the isopropyl beta-D-thiogalactopyranoside
      (IPTG)-induced overexpressed protein product was characterized following complete
      purification. Comparison of the sll1722 sequences with other MIPS sequences and
      its phylogenetic analysis revealed that the Synechocystis MIPS gene is quite
      divergent from the others.

PMID- 14730449
TI  - Modeling of stimulation-secretion coupling in a chromaffin cell.
AB  - We constructed a chromaffin cell model for analysis of stimulation-secretion
      coupling in computer simulation studies. The model includes mechanisms involved
      in the excitatory synapse, voltage-dependent Na(+), K(+) and Ca(2+) channels,
      Ca(2+)-activated K(+) channels (SK type), buffered Ca(2+) diffusion, Ca(2+)
      extrusion, fluorescent Ca(2+) indicators and Ca(2+)-triggered exocytosis.
      Calculations of the modeled mechanisms were carried out using the NEURON
      simulation environment (Hines and Carnevale, Neural Computation 9:1179-1209,
      1997). A set of parameter values was determined so as to fit basic experimental
      results reported in the literature. The model was also applied to simulate our
      experimental results obtained from chromaffin cells in the perfused rat adrenal
      medulla. Observed profiles of Ca(2+)responses induced by electrically stimulating
      the splanchnic nerve with various frequencies (1-50 Hz) were adequately simulated
      with minor readjustments of parameter values for Ca(2+)influx and extrusion.
      Secretory responses measured at the same time as the Ca(2+)responses were also
      simulated with consideration of a time constant to detect catecholamines in the
      experiment. Similarly, model simulations reproduced both Ca(2+)responses and
      secretory responses evoked by elevations of the extracellular K(+) concentration
      for different periods. The results suggest that the presented model provides a
      useful tool for analyzing and predicting quantitative relations in various events
      occurring in stimulation-secretion coupling in chromaffin cells.

PMID- 14730450
TI  - Voxel-based computational models of real human anatomy: a review.
AB  - Computational models of human anatomy are mathematical representations of human
      anatomy designed to be used in dosimetry calculations. They have been used in
      dosimetry calculations for radiography, radiotherapy, nuclear medicine, radiation
      protection and to investigate the effects of low frequency electromagnetic
      fields. Tomographic medical imaging techniques have allowed the construction of
      digital three-dimensional computational models based on the actual anatomy of
      individual humans. These are called voxel models, tomographic models or phantoms.
      Their usefulness lies in their faithful representation of human anatomy and the
      flexibility they afford by being able to be scaled in size to match the required
      human dimensions. Segmenting medical images in order to make voxel models is very
      time-consuming so semi-automatic segmentation techniques are being developed.
      Some 21 whole or partial body models currently exist and more are being prepared.
      These models are listed and discussed.

PMID- 14730453
TI  - Plastic solutions for orthopaedic problems.
AB  - INTRODUCTION: Infection and exposure of the implant may occur in 1-12% of
      patients operated on for arthroplasty or osteosynthesis. Variables such as tissue
      viability, presence of infection, exposure of osteosynthesis material and patient
      related factors contribute to the lack of general consensus regarding the
      management of these defects. MATERIALS AND METHODS: Between January 1999 and
      January 2001, six patients were treated for complex soft-tissue defects following
      various orthopaedic procedures at the Department of Plastic Surgery in the
      Slotervaartziekenhuis in Amsterdam, a rheuma-orthopaedic orientated hospital. All
      patients were initially treated by radical debridement and vacuum-assisted
      closure (VAC) system of the wound. After 1 week, this was followed by
      transplantation of a pedicled or free flap to cover the defect. We studied the
      medical history, initial orthopaedic procedure, wound treatment, transplanted
      flap and outcome of plastic surgery in this group. RESULTS: Plastic surgical
      intervention led to wound closure in all cases. In only one case was the
      osteosynthesis material removed because of osteomyelitis. CONCLUSIONS: We
      conclude that the earlier coverage with vital tissue is obtained, the lower the
      incidence of infection. Early consultation by a plastic surgeon will increase a
      positive outcome of treatment of complex tissue defects.

PMID- 14730452
TI  - A sensitive and restricted enzyme-linked immunosorbent assay for detecting a
      heterogeneous antibody population in serum from people suffering from a new
      variant of endemic pemphigus.
AB  - We recently described a new variant of endemic pemphigus foliaceus (EPF) in El
      Bagre, Colombia, that resembles Senear-Usher syndrome and identified
      autoantibodies to desmoglein 1 (Dsg1), as well as to multiple known and unknown
      antigens including plectins, in the serum of these patients. Here, we developed a
      cost-effective ELISA assay capable of detecting the heterogeneous antibody
      population observed in these EPF patients, and useful for serum epidemiological
      studies. A protein extract obtained from trypsin-digested fresh bovine skin and
      further purified on a concanavalin A matrix was used as antigen. This extract
      contains an important conformational epitope (a 45 kDa tryptic fragment of the
      Dsg1 ectodomain), which is recognized by antibodies in serum from patients with
      all varieties of pemphigus foliaceus (PF), and from half of those with pemphigus
      vulgaris with active clinical disease. The cut-off and threshold values were
      normalized using human serum obtained from both endemic and non-endemic areas for
      PF. The efficiency of this ELISA was tested using 600 serum samples from controls
      and patients diagnosed with EPF, non-endemic PF and other bullous diseases. The
      overall sensitivity and specificity of the assay were determined to be 95% and
      72%, respectively, with reproducibilities of 98% (intraassay) and 95%
      (interassay). Comparing the ELISA with other tests to detect EPF autoantibodies,
      this ELISA was the most sensitive, followed by direct immunofluorescence (DIF),
      indirect immunofluorescence using anti-IgG4 monoclonal antibodies and
      immunoprecipitation (IP), respectively. The most specific assay was IP, followed
      by DIF. Immunoblotting to Dsg1 exhibited both poor sensitivity and poor
      specificity, although plectins were well visualized. We conclude that this ELISA
      is an excellent tool for field serological studies, allowing testing of multiple
      serum samples simultaneously and for detecting, with appropriate restriction and
      sensitivity, the heterogeneous antibody population seen in patients with this
      variant of EPF. Finally, autoantibody serum levels obtained with this ELISA
      correlated well with the clinical activity and extent of disease in patients with
      El Bagre EPF.

PMID- 14730454
TI  - Expression of oligodendrocyte lineage genes in oligodendroglial and astrocytic
      gliomas.
AB  - The oligodendrocyte lineage genes OLIG1 and OLIG2 have been reported as potential
      diagnostic markers for oligodendrogliomas [Lu et al. (2001) Proc Natl Acad Sci
      USA 98:10851-10856; Marie et al. (2001) Lancet 358:298-300]. We investigated the
      mRNA expression of OLIG1 and OLIG2, as well as four other genes involved in
      oligodendrocyte development ( E2A, HEB, NKX2.2, and PDGFRA) in a panel of 70
      gliomas, including 9 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 5
      oligoastrocytomas, 10 anaplastic oligoastrocytomas, 10 diffuse astrocytomas, 10
      anaplastic astrocytomas, and 15 glioblastomas. Most tumors demonstrated higher
      transcript levels of these genes as compared to non-neoplastic adult brain
      tissue. Four glioblastomas showed markedly increased PDGFRA mRNA expression due
      to PDGFRA gene amplification. Statistical analyses revealed no significant
      expression differences between oligodendroglial and astrocytic tumors. In
      oligodendroglial tumors, expression of the six genes was not significantly
      correlated to loss of heterozygosity on chromosome arms 1p and 19q. Thus,
      expression of the investigated oligodendrocyte lineage genes is up-regulated
      relative to non-neoplastic brain tissue in the majority of oligodendroglial and
      astrocytic tumors, suggesting that glioma cells are arrested in or recapitulate
      molecular phenotypes corresponding to early stages of glial development. However,
      the determination of mRNA expression of these genes by means of reverse
      transcription-PCR does not appear to be diagnostically useful as a marker for
      oligodendrogliomas.

PMID- 14730457
TI  - No oculomotor plant, no final common path.
AB  - The assumption that there is an oculomotor plant, a fixed relationship between
      motoneuron firing rate and eye position, is disproved by brainstem recording
      studies showing that this relationship depends on which supernuclear subsystem
      determines firing rate. But it remains possible that there is a final common path
      (FCP), a fixed relationship between firing rate and muscle force. But then,
      brainstem recording studies predict that lateral rectus (LR) forces (and probably
      medial rectus (MR) forces, as well) will be higher in converged than in
      unconverged gaze for a given eye position. We recently measured these forces and
      found that they are slightly lower in convergence, disproving the FCP hypothesis.
      Thus, even the relationship between motoneuron firing rate and muscle force is
      under supernuclear control. What peripheral oculomotor articulations could vary
      the relationship of firing rate to muscle force?: (1) Actively movable EOM
      pulleys could alter oculorotary muscle force for a given oculorotory innervation
      by altering muscle lengths. (2) 'Outer' motoneurons may function as gamma
      efferents in conjunction with palisade endings and non-twitch global EOM fibers.
      (3) Complex nonlinear interactions likely arise among both parallel and serially
      connected muscle fibers.

PMID- 14730455
TI  - Glioblastoma cells release factors that disrupt blood-brain barrier features.
AB  - The blood-brain barrier (BBB), mediated by endothelial tight junctions, is
      defective in malignant gliomas such as glioblastoma, resulting in cerebral edema
      and contrast enhancement upon neuroradiological examination. The mechanisms
      underlying BBB breakdown are essentially unknown. Since non-neoplastic astrocytes
      are required to induce BBB features of cerebral endothelial cells, it is
      conceivable that malignant astrocytes have lost this ability due to
      dedifferentiation. Alternatively, glioma cells might actively degrade previously
      intact BBB tight junctions. To examine the latter hypothesis, we have employed a
      transepithelial electrical resistance breakdown assay using monolayers of the C7
      subclone of Madin-Darby canine kidney (MDCK-C7) cells forming tight junctions
      similar to those of BBB endothelial cells. We found that glioblastoma primary
      cells co-cultured with the MDCK-C7 monolayer (without direct contact of the two
      cell types) resulted in marked breakdown of electrical resistance, whereas
      primary cultures derived from low-grade gliomas (fibrillary astrocytoma,
      oligoastrocytoma) showed delayed or no effects. These results suggest that
      malignant gliomas have acquired the ability to actively degrade tight junctions
      by secreting soluble factors, eventually leading to BBB disruption within invaded
      brain tissue.

PMID- 14730458
TI  - Quantification of recti eye muscle paths in high myopia.
AB  - PURPOSE: To elucidate the etiology of an acquired, restrictive motility disorder
      in patients with high myopia. METHODS: Thirty-three orbits were imaged using a
      Siemens Magnetom or Siemens Vision (both 1.5 Tesla) MRI (magnetic resonance
      imaging) scanner, applying a head coil. Coronal T1-weighted, spin-echo images
      were obtained. Orbits of three different patient groups were analyzed. Group 1 (n
      = 14): patients with high axial myopia and restricted eye motility (average axial
      length = 31.4 mm; refractive error more than -15 D). Group 2 (n = 8): subjects
      with high axial myopia and normal eye motility (average axial length = 29.2 mm).
      Controls (n = 11): emmetropic subjects with normal eye motility. RESULTS: Highly
      myopic patients showed significant displacements of recti EOMs in comparison to
      the controls. Mean displacements as measured in the plane 3 mm anterior to the
      globe-optic nerve junction in primary gaze were, in group 1: lateral rectus (LR)
      2.9 mm (2.5 downward, 1.4 medial), medial rectus (MR) 1.3 mm downward. In group
      2: LR 1.4 mm (1.3 downward, 0.6 medial) and MR 1.2 mm downward. In both groups 1
      and 2, the inferior rectus (IR) was displaced 1.3 mm medially and upwards. In
      both groups of myopic patients the superior rectus (SR) was displaced 1.5 mm
      medially and downwards. CONCLUSIONS: In patients with high axial myopia,
      displacements of all recti EOMs can be detected by MRI. However, displacement of
      the LR into the lateral and inferior quadrant of the orbit is significantly
      greatest. We therefore assume LR displacement to be a major pathophysiological
      factor for the restrictive motility disorder in high myopia. EOM dislocations can
      be explained by myopia-associated alterations in the orbital connective tissues
      confining EOM positions in relation to the orbital wall.

PMID- 14730459
TI  - Mechanical interdependence of version and vergence eye movements.
AB  - In this paper, the authors investigate whether the idea of independent control of
      version and vergence eye movements is compatible with the mechanics of the eye
      plant. By computing the change in the axes of action of the eye muscles as a
      function of ocular vergence, they prove that, regardless of the muscle pulley
      locations, the required muscle activity for vertical version depends on the
      initial vergence angle. The binocular extension of Listing's law ('L2') describes
      how the torsional orientation of the eye depends on both gaze direction and
      ocular convergence. The authors show that for each vergence angle there is a
      range of possible muscle pulley locations that would cause independent control of
      version and vergence to result in L2. They also show that this mechanical
      explanation of L2 requires that the muscle pulleys move as a function of
      vergence.

PMID- 14730460
TI  - Multifocal stimulation techniques in ophthalmology -- Current knowledge and
      perspectives.
AB  - The purpose of this paper is to give a brief overview on the application of
      multifocal stimulation techniques in ophthalmology. The use of m-sequences as a
      stimulus sequence allows a high-resolution topographic mapping of sensory
      function. Outer retinal dysfunction can readily be detected with the multifocal
      ERG (mfERG). When the inner retinal contribution to the mfERG response is
      enhanced through adapting the stimulation sequence, the sensitivity of the mfERG
      to detect retinal dysfunction in glaucoma can be increased. Testing of the entire
      visual pathway with multifocal cortical evoked visual potentials is also possible
      and recent studies have focused on reducing interindividual variability. The use
      of m-sequence stimulation in magnetic encephalography offers new ways to study
      visual processing without the need to apply electrodes.

PMID- 14730461
TI  - Simulation of oculomotility in Craniosynostosis patients.
AB  - Craniosynostosis syndromes can be associated with missing extraocular muscles, or
      muscles with abnormal insertions, and so provide useful test cases for assessing
      our understanding of the mechanics of the extraocular muscles. Patient with
      craniosynostosis syndromes often show eye movements in which a horizontal
      movement by one eye is accompanied by upshoot or downshoot in the other eye. An
      hypothesis which has been put forward to explain these movements is that the
      muscles in the patients are excyclorotated and that the upshoots and downshoots
      follow directly from the application of Hering's law of equal innervation. We
      modelled the mechanics of the excyclorotated muscles and verified this
      hypothesis. However, excyclorotation of the orbit often occurs in combination
      with anomalous muscle anatomy in craniosynostosis syndromes. In keeping with this
      finding, we have found that surgical transposition of the rectus muscles is
      insufficient by itself to correct the anomalous eye movements, but that
      transposition in combination with weakening of the obliques is effective.

PMID- 14730462
TI  - Adaptive control of pursuit eye movements in humans.

PMID- 14730463
TI  - The life of Johann Benedict Listing.

PMID- 14730466
TI  - Biological therapy for psoriasis: an overview of infliximab, etanercept,
      efalizumab and alefacept.
AB  - Psoriasis is a chronic skin disorder that affects approximately 2% of the US and
      European population. Over the last several years one of the major foci in
      psoriasis research has been the development of biological therapies for this
      disease. The aim of these therapies is to provide selective, immunologically
      directed intervention with fewer side effects than traditional therapies. This
      article will review the progress of four biological agents that are available or
      under investigation for clinical use: infliximab (Centocor Inc), etanercept
      (Amgen Inc/Wyeth), efalizumab (Genentech Inc/XOMA Ltd/Serono SA) and alefacept.

PMID- 14730467
TI  - New anticoagulants for venous thromboembolic disease.
AB  - Venous thromboembolic disease, including deep vein thrombosis and pulmonary
      embolism, is a cause of significant mortality and morbidity. In the US,
      approximately 260000 cases are diagnosed annually. Current drugs for the
      prevention and treatment of venous thromboembolism (VTE) include heparin, low
      molecular-weight heparins and warfarin. Since they possess several disadvantages,
      researchers are investigating improved anticoagulants. To understand how any
      promising anticoagulant would work, a review of the pathophysiology and
      regulation of the coagulation cascade is provided. The more prominent drugs
      reviewed include tissue factor pathway inhibitor protein, nematode anticoagulant
      protein, Factor IX inhibitors, anti-Factor Xa inhibitors (DX-9065a (Daiichi
      Seiyaku Co Ltd), YM-60828 (Yamanouchi Pharmaceutical Co Ltd), fondaparinux,
      idraparinux (Sanofi-Synthelabo/NV Organon)), selective thrombin inhibitors (oral
      heparin, ximelagatran (AstraZeneca plc)) and enhancers of natural anticoagulants
      (activated protein C, ART-123 (Asahi Kasei Pharma Corp)).

PMID- 14730468
TI  - Canertinib pfizer.
AB  - Canertinib, a water-soluble, orally available analog of PD-169414 (Pfizer Inc),
      is an EGFR tyrosine kinase inhibitor under development by Pfizer Inc as a
      potential treatment for cancer.

PMID- 14730469
TI  - BNP-7787 (BioNumerik/Baxter Oncology/Grelan).
AB  - BioNumerik Pharmacology Inc, Baxter Oncology GmbH (formerly ASTA Medica AG) and
      Grelan Pharmaceutical Co Ltd are developing BNP-7787 for the potential reduction
      of toxicity associated with cisplatin and carboplatin treatment in cancer
      patients.

PMID- 14730471
TI  - Recurrent thromboembolism in cancer patients: incidence and risk factors.
AB  - In contrast with the paucity of data on the risk of a first episode of thrombosis
      in cancer patients, the frequency of recurrent thromboembolism in patients with
      malignancy has been extensively investigated, both during anticoagulation and
      after its cessation. Cancer patients are more likely to develop recurrent
      thromboembolism and major bleeding during anticoagulation than patients without
      malignancies. These events are more pronounced during the first weeks of
      treatment and increase with cancer severity. Since they are not associated with
      anticoagulant intensities outside the therapeutic range, possibilities for
      improvement using the current paradigms of anticoagulation seem limited and new
      treatment strategies should be developed. In this regard, the use of low
      molecular-weight heparins for initial treatment and long-term anticoagulation in
      cancer patients with venous thrombosis seems promising. Furthermore, patients
      with active cancers exhibit a particularly high risk of recurrent venous
      thromboembolism after the cessation of anticoagulation. In view of the persisting
      high risk for recurrent thrombotic events in cancer patients, and the acceptable
      risk of bleeding, prolonged warfarin treatment should be considered in such
      patients for as long as the cancer is active.

PMID- 14730472
TI  - Low-molecular-weight heparin or oral anticoagulation for secondary prevention of
      deep vein thrombosis in cancer patients.
AB  - Thrombosis in the cancer patient is a unique problem. Cancer patients with acute
      venous thromboembolism are at increased risk of its recurrence compared with
      noncancer patients. Cancer patients are also at increased risk of anticoagulant
      associated bleeding compared with noncancer patients. Finally, many cancer
      patients have a compromised quality of life and recurrent thrombosis has an
      additional negative impact on them. In order to optimize treatment of acute
      venous thromboembolism in cancer patients, the following outcomes must be
      considered: a reduction in the rate of recurrent venous thromboembolism, a
      reduction in the risk of bleeding compared to that seen with current
      anticoagulant treatment regimens, and a positive impact on the quality of life of
      the patient.

PMID- 14730473
TI  - Low-molecular-weight heparins: beyond thrombosis in the management of the cancer
      patient.
AB  - Thrombosis is a common complication in patients with cancer and large,
      retrospective population-based studies indicate that cancer patients with
      clinical venous thromboembolism have a poorer prognosis than those without. The
      risk of thrombosis appears to differ between different tumor types. Beyond the
      important impact that fatal pulmonary embolism may have on cancer outcome, the
      activated coagulation serine proteases generated by cancer cells through the
      peritumor activation of blood coagulation pathways are able to interact with cell
      surface protease receptors. These, in turn, mediate several cellular events
      resulting in important phenotypic alterations in tumor cell behavior.

PMID- 14730474
TI  - Venous thromboembolism in medical patients--the scope of the problem.
AB  - The risk of venous thromboembolism (VTE) in medical patients has been
      substantially underestimated and prophylaxis is used far less than it is in
      surgical patients, reflecting the scarcity of evidence supporting antithrombotic
      therapy in nonsurgical settings. Reports of the frequency of deep venous
      thrombosis (DVT) in general medical patients in the absence of prophylaxis vary
      from 10 to 26%, depending on the methods used for diagnosis of DVT and the
      patient population studied. The risk in specific groups may be higher and may
      exceed that reported in low- or moderate-risk surgical patients. Data from
      several studies show that DVT developed in approximately 55% of patients with
      stroke, 24% of patients with myocardial infarction, and, in general medical
      populations, congestive heart failure, respiratory distress and/or underlying
      chest infections appeared to increase the risk of VTE. The frequency of VTE in
      patients with congestive heart failure has been reported to be as high as 40%. In
      a study among patients in a medical intensive care unit, it was found that 33%
      had VTE, of which 48% were proximal leg thromboses. Many other medical conditions
      increase the risk of thromboembolic events. These include malignant disease,
      which is commonly associated with a hypercoagulable state; inflammatory
      conditions such as systemic lupus erythematosus and inflammatory bowel disease;
      coma; and nephrotic syndrome. Accurate risk assessment and prompt implementation
      of appropriate prophylaxis, selected on the basis of evidence from well-designed,
      controlled clinical trials, may reduce future morbidity and mortality due to VTE
      in medical patients.

PMID- 14730475
TI  - DVT Prevention: what is happening in the "real world"?
AB  - Pulmonary embolism (PE) and deep venous thrombosis (DVT) remain major problems in
      medicine that receive less attention from healthcare professionals and the public
      than either coronary artery disease or acute myocardial infarction. Furthermore,
      strategies proven to minimize the frequency of PE and DVT are not widely employed
      on a consistent and effective basis. The problem is widespread and affects
      patients in acute care hospitals, rehabilitation hospitals, and skilled nursing
      facilities, as well as high-risk individuals at home. Internists, general
      practitioners, and family doctors confront the greatest challenges in
      implementing appropriate prophylaxis. Models for effective change exist in
      cardiovascular and surgical practices where the imperative for prevention of
      further disease is insisted upon and ingrained in the culture of clinicians. We
      will review the epidemiology of venous thromboembolism, strategies for the
      primary and secondary prevention of PE and DVT, "real world" use of prophylaxis,
      barriers to change that exist in the "real world," and initiatives to improve day
      to-day practice. We will conclude by posing 10 questions for future research on
      this topic.

PMID- 14730476
TI  - Why is factor Xa not a better target than factor IIa for therapeutic inhibition
      of coagulation?
AB  - The rapid development of new and selective anticoagulant agents has triggered the
      question of which activated coagulation factor would be a better target for the
      inhibition of coagulation. Indirect comparisons between studies on the different
      drugs are problematic due to the plethora of characteristics that may differ
      between them. Even head-to-head comparisons in the same study may not determine
      the optimal target due to differences in pharmacokinetics between the agents.
      Therefore, the answer to this question relies on theoretical speculations based
      on knowledge of some of the factors that seem to have an influence on efficacy
      and safety. Ultimately, drugs with equal pharmacokinetic characteristics that are
      administered in equipotent doses may have a similar global effect on coagulation,
      independent of the inhibitory mechanism. Conversely, the differentiated
      inhibition of the coagulation protease on vascular receptors may play a greater
      role for effects that are not traditionally considered as part of hemostasis.

PMID- 14730477
TI  - Factor Xa is a superior target to factor IIa for antithrombotic therapies.

PMID- 14730478
TI  - Confirmation of linkage to chromosome 1q for peak vertebral bone mineral density
      in premenopausal white women.
AB  - Peak bone mineral density (BMD) is a highly heritable trait and is a good
      predictor of the risk of osteoporosis and fracture in later life. Recent studies
      have sought to identify the genes underlying peak BMD. Linkage analysis in a
      sample of 464 premenopausal white sister pairs detected linkage of spine BMD to
      chromosome 1q (LOD 3.6). An independent sample of 254 white sister pairs has now
      been genotyped, and it also provides evidence of linkage to chromosome 1q (LOD
      2.5) for spine BMD. Microsatellite markers were subsequently genotyped for a 4-cM
      map in the chromosome 1q region in all available white sister pairs (n=938), and
      a LOD score of 4.3 was obtained near the marker D1S445. Studies in the mouse have
      also detected evidence of linkage to BMD phenotypes in the region syntenic to our
      linkage finding on chromosome 1q. Thus, we have replicated a locus on 1q
      contributing to BMD at the spine and have found further support for the region in
      analyses employing an enlarged sample. Studies are now ongoing to identify the
      gene(s) contributing to peak spine BMD in women.

PMID- 14730481
TI  - [Medical journals and conflicts of interests with the pharmaceutical industry].

PMID- 14730479
TI  - Are variants in the CAPN10 gene related to risk of type 2 diabetes? A
      quantitative assessment of population and family-based association studies.
AB  - The calpain-10 gene (CAPN10) on chromosome 2q37.3 was the first candidate gene
      for type 2 diabetes (T2D) identified through a genomewide screen and positional
      cloning. One polymorphism (UCSNP-43: G-->A) and a specific haplotype combination
      defined by three polymorphisms (UCSNP-43, -19, and -63) were linked to an
      increased risk of T2D in several populations. To quantitatively assess the
      collective evidence for the effects of CAPN10 on risk of T2D, we conducted a meta
      analysis of both population-based and family-based association studies. We
      retrieved data from the MEDLINE, PubMed, and Online Mendelian Inheritance in Man
      databases, as well as from other relevant reports and abstracts published up to
      July 2003. From a total of 26 studies with primary data (21 population-based
      studies: 5,013 cases and 5,876 controls; 5 family-based studies: 487 parent
      offspring trios), we developed a summary database that contains variables of
      study design, study population/ethnicity, specific polymorphisms and haplotype
      combinations in CAPN10, and diabetes-related metabolic phenotypes. For population
      based studies, we used both fixed-effects and random-effects models to calculate
      the pooled odds ratio (OR) and 95% confidence interval (CI) for the associations
      of CAPN10 genotypes with the risk of T2D. We also calculated weighted mean
      differences for the associations between CAPN10 and diabetes-related quantitative
      traits. Under either an additive or a dominant effect model, we found no
      statistically significant relation between CAPN10 genotypes in the UCSNP-43 locus
      and T2D risk. However, under a recessive model, individuals homozygous for the
      common G allele had a statistically significant 19% higher risk of T2D than
      carriers of the A allele (OR 1.19; 95% CI 1.07-1.33). The association between the
      112/121 haplotype combination and T2D risk appeared to be overestimated by
      several initial small studies with positive findings (OR 1.38; 95% CI 1.04-1.84).
      After we removed these initial studies, this association became nonsignificant
      (OR 1.11; 95% CI 0.91-1.35). Moreover, we found no evidence for the associations
      between the UCSNP-43 G/G genotype and the 112/121 haplotype combination and
      metabolic phenotypes. Our meta-analysis of family-based studies showed only an
      overtransmission of the rare allele C in UCSNP-44 from heterozygous parents to
      their affected offspring with T2D. Our analysis indicates that inadequate
      statistical power, racial/ethnic differences in frequencies of alleles,
      haplotypes and haplotype combinations, potential gene-gene or gene-environment
      interactions, publication bias, and multiple hypothesis testing may contribute to
      the significant heterogeneity in previous studies of CAPN10 and T2D. Our findings
      also suggest that both large-scale, well-designed association studies and
      functional studies are warranted to either reliably confirm or conclusively
      refute the initial hypothesis regarding the role of CAPN10 in T2D risk.

PMID- 14730483
TI  - [Can the behavioural phenotype of fragile X syndrome be attributed to mental
      retardation and to attention deficit hyperactivity disorder?].
AB  - INTRODUCTION: Fragile X syndrome (FXS) reveals itself as dysmorphic stigmata,
      systemic manifestations, neurological symptoms and cognitive-behavioural
      manifestations. Mental retardation (MR) and attention deficit hyperactivity
      disorder (ADHD) nearly always appear as examples of this last case, but most
      patients also present a series of fairly common behavioural characteristics. The
      most characteristic types of conduct seen in FXS include: language problems, lack
      of attention, hyperactivity, anxiety, shyness, behavioural problems,
      stereotypical hand flapping, gaze aversion, obstinacy and aggressiveness. AIMS:
      The purpose of this work is to determine which behavioural aspects of the
      syndrome are linked to the genetic specificity and are not, therefore, determined
      by MR and ADHD. PATIENTS AND METHODS: Three groups of patients were compared: 30
      children diagnosed as suffering from FXS, 30 children with MR caused by diverse
      aetiologies and 323 children diagnosed as suffering from ADHD. RESULTS: It was
      found that there were no significant differences between the IQ and the age of
      the FXS and MR groups. To determine the behavioural characteristics of the three
      groups the parents of the patients answered Achenbach's CBCL/4-18 survey.
      CONCLUSIONS: The results obtained show that certain types of conduct that are
      very typical of FXS are represented significantly more frequently in the FXS
      group than in the groups of patients with MR and ADHD. This behaviour includes:
      timidity, attachment to adults, shyness, repetition of certain actions over and
      over again, pronunciation and speech problems, fear of animals, situations or
      places, and concern for tidiness and cleanliness. These findings lend support to
      the idea that the behavioural phenotype of FXS is linked to the genetic disorder
      and is not, therefore, a consequence of MR or ADHD.

PMID- 14730480
TI  - Genomewide linkage analysis for internal carotid artery intimal medial thickness:
      evidence for linkage to chromosome 12.
AB  - Carotid intimal medial thickness (IMT) is a heritable quantitative measure of
      atherosclerosis. A genomewide linkage analysis was conducted to localize a
      quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured
      in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the
      Framingham Heart Study Offspring cohort. B-mode carotid ultrasonography was used
      to define mean IMT of the carotid artery segments. Multipoint variance-component
      linkage analysis was performed. Evidence for significant linkage to internal
      carotid artery (ICA) IMT (two-point log odds [LOD] score 4.1, multipoint LOD
      score 3.4) was found 161 cM from the tip of the short arm of chromosome 12; these
      results were confirmed using the GENEHUNTER package (multipoint LOD score 4.3).
      No LOD scores >2.0 were observed for common carotid artery (CCA) IMT. Association
      analysis of a single-nucleotide-polymorphism variant of SCARB1 (minor allele
      frequency 0.13), a gene in close proximity to the region of peak linkage,
      revealed a protective association of the missense variant allele in exon 1 of
      SCARB1, with decreased ICA IMT compared with subjects homozygous for the common
      allele. Although the exon 1 variant contributed 2% to overall variation in ICA
      IMT, there was no significant change in the peak LOD score after adjustment in
      the linkage analyses. These data provide substantial evidence for a QTL on
      chromosome 12 influencing ICA IMT and for association of a rare variant of
      SCARB1, or a nearby locus, with ICA IMT. Because this rare SCARB1 variant does
      not account for our observed linkage, further investigations are warranted to
      identify additional candidate-gene variants on chromosome 12 predisposing to
      atherosclerosis phenotypes and clinical vascular disease.

PMID- 14730484
TI  - [Early diagnosis of neurometabolic diseases by tandem mass spectrometry.
      Acylcarnitine profile from cord blood].
AB  - INTRODUCTION: Tandem mass spectrometry (MS/MS) provides a multi-analyte
      technology for the detection of disorders characterised by the presence of
      abnormal concentrations of metabolites related to neurological deterioration. It
      has been recently recommended the use of this technique for early diagnosis of
      inherited metabolic diseases using cord blood. AIMS: To draw the attention to the
      inherited metabolic diseases detected by tandem mass spectrometry and to
      establish reference values for acylcarnitines in cord blood. PATIENTS AND
      METHODS: One hundred and thirty cord blood specimens from full-term and normal
      birth weight children (78 males and 52 females) were analysed by MS/MS. RESULTS
      AND CONCLUSION: Reference values for acylcarnitines from cord blood by MS/MS as a
      tool for the diagnosis of some neurometabolic diseases are provided. No
      statistical significant difference between sexes was found. We reviewed the
      literature related to the diagnosis of inherited metabolic diseases, with
      emphasis in fatty acid mitochondrial beta-oxidation using MS/MS.

PMID- 14730485
TI  - [Use of magnetic resonance imaging to evaluate morphological disorders in the
      brains of patients with sickle cell anaemia].
AB  - INTRODUCTION: Blocked blood flow in the brain of patients with sickle cell
      anaemia (SCA) gives rise to disorders in this organ and, occasionally, courses
      with no clinical symptoms. AIMS: Our objective was to determine the most common
      lesions in the brains of patients with SCA in the eastern region of Cuba.
      PATIENTS AND METHODS: We conducted a study with children and adults with SCA, who
      were voluntarily included in the research protocol. The 28 adult patients had no
      history of vaso-occlusive crises of the central nervous system, and their ages
      ranged from 17 to 48 years. In addition, 50 paediatric-aged patients between the
      ages of 2 and 17 years were evaluated. Images were obtained with the Cuban
      magnetic resonance imaging equipment Giroimag 01 at 0.05 T. RESULTS: Both studies
      showed that cortical atrophy (CA) is the most frequent brain lesion among those
      found in the population of patients evaluated. The study revealed 35.7% of
      patients with silent lesions in adults and 18% in the children. CONCLUSIONS: CA
      is the lesion that is most commonly seen in the population studied. The brain
      lesions that were found are possibly triggered by the effect of blockages in the
      blood flow in the brain. A population study must be conducted in order to
      determine the first disorders triggered by the blocked blood flow in the brains
      of these patients. There is also a need to evaluate the possible risk factors
      that favour the development of these lesions.

PMID- 14730486
TI  - [Relationship between neurological deficit and intelligence quotient in children
      and adolescents].
AB  - INTRODUCTION: The relationship between developmental and mental deficits due to
      genetic or acquired causes is well established. However the possible relationship
      between neurological signs and intellectual development has not been sufficiently
      studied. OBJECTIVE: We have conducted a transversal study to test the possible
      association between neurological signs and psychometric measures in children and
      young adolescents. PATIENTS AND METHODS: 123 patients were neurologically
      explored (ages between 54-185 months), 36 girls and 87 boys. These subjects were
      neurologically and psychometrically tested during a period of 3 years.
      Contingency tables, chi squared tests, discriminant analysis and ROC curves were
      used for statistical analysis. This statistic allowed to establish the
      contingencies between neurological signs (presence or absence) and intelligence
      quotient (IQ) groups (low and normal scores). RESULTS: The results showed a
      statistically significant relationship between IQ and the presence of 7
      neurological signs (chi2=6.213; p=0.013). The discriminant analysis classified
      correctly 77.2% of subjects. The ROC curves indicated a high sensitivity and
      specificity if subjects presented more than 3 neurological signs. The frequency
      analysis established the more discriminant neurological signs. CONCLUSIONS: The
      obtained results in children with learning and behavioural disabilities suggest
      comorbidity between low IQ and neurological signs. This association is more
      marked in the group of children than in the pre- and adolescent group.

PMID- 14730487
TI  - [Intelligence, memory and malingering: correlation between scales].
AB  - OBJECTIVES: To validate the test of memory malingering (TOMM), and to study the
      influence of intelligence and memory on its performance in brain injury patients.
      PATIENTS AND METHODS: A total of 30 patients with traumatic head injury were
      included in the study. All patients were assessed with the Complutense verbal
      learning test, the Visual Reproduction subtest of the Wechsler memory scale
      revised, the Boston naming test, two fluency tests (FAS, and animals), the
      Wechsler adult intelligence test-III, and with the TOMM. Cognitive results below
      1 standard deviation (SD) from normative data were considered 'abnormal'. A
      parametric correlation between TOMM scores and cognitive tests was used to detect
      whether memory and intelligence were affecting TOMM performance. Statistical
      significance was set up at p<0.05. RESULTS: Between 46.1% (Boston) and 81.4%
      (WAIS-III performance IQ) of the sample presented cognitive deficits. Up to 83.3%
      of the patients scored above the cutoff point suggestive of malingering in the
      TOMM (45/50). Significance correlations were found between TOMM scores and memory
      or intelligence indexes. DISCUSSION: The TOMM is a useful tool to detect
      malingering in head injured patients. Effects of low intelligence coefficients,
      as well as memory deficits should be considered in clinical practice when
      evaluating patients with TOMM scores suggestive of malingering.

PMID- 14730488
TI  - [Ischemic stroke, secondary to fibromuscular dysplasia: a case report].
AB  - INTRODUCTION: Fibromuscular dysplasia is an infrequent angiopathy that occurs
      more often in young women. It consists in a series of heterogeneous histological
      changes that finally lead to the narrowing of arteries. Clinical manifestations
      depend on the vessel involved, but high blood pressure (renal artery involvement)
      and stroke (carotid artery involvement) are the most common. Little has been
      published about this process in recent years. CASE REPORT: A 30-year-old female
      with extensive infarction of the right middle cerebral artery caused by
      obstruction of the internal carotid artery. Arteriographical examination revealed
      the dissection of the four supra-aortic trunks together with alterations to the
      renal artery. The patient's age and the involvement of the four cerebral arteries
      with irregular stenoses led us to consider a fibromuscular dysplasia (FMD) as the
      first diagnostic option. A conservative attitude was adopted towards the vascular
      lesions and therapy was carried out with a view to rehabilitating the
      neurological deficits. DISCUSSION: Brain FMD can be asymptomatic and is often
      diagnosed by chance. The usual clinical presentation is a stenosis-related
      ischemic stroke, arterial obstruction or arterio-arterial thromboembolism.
      Arteriography or magnetic resonance angiography are useful for diagnosis; the
      involvement of different supra-aortic vessels is characteristic. Despite the good
      results shown by percutaneous transluminal angioplasty, there is still a need for
      prospective studies that determine the optimal treatment for this pathology.

PMID- 14730489
TI  - [Clinical and neuroimaging findings in a family with CADASIL associated to C475T
      mutation].
AB  - INTRODUCTION: The term CADASIL (cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy) refers to an autosomal dominant
      hereditary arteriopathy of the brain that is characterised by headache, recurring
      strokes and progressive cognitive deterioration. We report the case of another
      family with CADASIL and emphasise the importance of a genetic study in its
      diagnosis. CASE REPORT: A 62-year-old female patient with repeating lacunar
      strokes, subcortical dementia and a family history of dementia and strokes.
      Neuroimaging studies conducted on the patient and her siblings showed signs of
      leukoencephalopathy and lacunar infarctions. The ultrastructural study of the
      biopsy performed on a sample of the patient's skin, which included five dermal
      vessels, did not show any electron-dense deposits. The genetic study revealed the
      presence of mutation C475T in exon 4 of NOTCH3. CONCLUSIONS: The possible
      presence of CADASIL must be suspected in patients with symptoms of
      cerebrovascular disease or dementia who present characteristic alterations in the
      magnetic resonance brain scan, especially when there is a compatible family
      history. The first choice diagnostic procedure must be a genetic study.

PMID- 14730490
TI  - [Characterization of neuronal ceroid lipofuscinosis in Venezuelan children].
AB  - INTRODUCTION: Neuronal ceroid lipofuscinosis (NCL), represents a group of
      inherited neurodegenerative disorders. Based on the age of the patient at onset,
      clinical course and ultrastructural morphology it has been identified three
      clinical types for the pediatric group: 1) Infantile NCL (INCL); 2) Late
      infantile NCL (LINCL); and 3) Juvenile NCL (JNCL). Other variants or atypical
      forms represent around 20% of the NCL in different populations. Genetic advances
      have made possible a better characterization, diagnostic and classification of
      these disorders. CASE REPORTS: We present the clinical, neurophysiological,
      neuroradiological, and morphological data from 6 patients with NCL, who were
      assessed at the pediatric neurology department of the Hospital Universitario de
      Maracaibo during a ten years period (1993 2003). All 6 cases corresponded with
      the late infantile form. Age of onset ranged form 2 to 5 years. For most of the
      patients initial symptoms included seizures, psychomotor delay, accompanied by
      macular degeneration and optic atrophy. The EEG was characterized by high voltage
      spikes elicited by low frequency photic stimulation, in 5 cases. Neuroimaging
      findings were characteristic of the late infantile form of the NCL. In three
      patients a decreased intensity of signal was seen in the thalami and putamen on
      T2-weighted images. The ultrastructural examination of the samples obtained
      through a biopsy showed curvilinear bodies in all patients. CONCLUSION: There is
      not epidemiological data of the NCL in Venezuela; it is presumed the presence of
      clinical forms and variants in the pediatric group. This first study could
      contribute to the knowledge and a better research of this group of disorders in
      our population.

PMID- 14730491
TI  - [Pyridoxine dependence: the importance of the clinical diagnosis and early
      treatment].
AB  - OBJECTIVE: We described the electroclinical features, evolution and family
      history of two patients with definitive diagnosis of pyridoxine dependency. CASE
      REPORTS: The first patient is a 15-month-old girl who at 1 month of age started
      with seizures and irritability. At two months of age, pyridoxine was prescribed
      with a good control of seizures. At five months of age withdrawal response
      provoked 7 days after seizures recurrence. Pyridoxine was reintroduced and
      seizures disappeared. Her sister, at two months of age, started with refractory
      seizures. This sister also had mental retardation and at four years, she died.
      Her brother, 16 years old, presents mental retardation, refractory epilepsy and
      progressive motor and cognitive impairment. At 3 months of age, he started with
      seizures and at 15 years of age, pyridoxine was prescribed with a significative
      improvement the number of seizures and a better visual connection. The second
      patient is a 4-month-old girl who started with clonic seizures at 3 days of age
      and she had a good response to pyridoxine. Withdrawal response provoked seizure
      recurrence at 48 hours. Pyridoxine was introduced immediately with total control
      of seizures. She had two cousins with seizures who died at 3 months and 3 years
      of age respectively. CONCLUSION: When dealing with an infant with refractory
      seizures which start in the first two years of life and without etiology, we
      should consider the diagnosis of pyridoxine dependency. Early diagnosis and
      treatment with pyridoxine is crucial to avoid high risk morbidity and mortality.
      All infants in the two first years of life with refractory seizures without
      etiology must be prescribed oral pyridoxine (50-200 mg per day).

PMID- 14730492
TI  - [Paroxysmal dyskinesias in children].
AB  - AIM AND DEVELOPMENT: The clinical, pathophysiological and genetic features of
      some of the paroxysmal movement disorders are reviewed. Paroxysmal idiopathic
      dyskinesias are genetically heterogeneous. Although some motor manifestations of
      epilepsy and paroxysmal dyskinesia may be difficult to differentiate clinically,
      the current understanding is that the two disorders are clinically distinct.
      However there are several recent reports of families in which different
      individuals have either disorder or both manifestations, with age-related
      expressions. Co-occurrence makes it likely that a common, genetically determined
      pathophysiologic abnormality is variably expressed in the cerebral cortex and in
      basal ganglia. CONCLUSION: The pathophysiology of paroxysmal dyskinesia is
      unknown. To date, despite strong suspicions, no ion channel gene mutations have
      been isolated.

PMID- 14730493
TI  - [Age-related memory disorder in basic medical care. Some conceptual and
      epidemiological considerations].
AB  - INTRODUCTION: Of all the age-related changes, those associated with the nervous
      system are of primordial importance and, although there are of course exceptions,
      brain deterioration is very widespread in the elderly. DEVELOPMENT: In both
      normal and pathological aging, on many occasions the first cognitive dysfunction
      to appear and the most affected is memory. Age-related memory disorder (ARMD) is
      a clinical state that is characterised by loss of memory in people aged 50 or
      over with no other explainable causation and which can be quite common because of
      its being linked to the normal aging process. Care of these patients involves
      high economic costs for the family and for society. Although the behavioural
      defects associated with ARMD are mild, compared to those found in dementias, they
      are disturbing and difficult for many middle-aged and elderly adults who perform
      intellectual activities. Yet, the memory disorder observed in the elderly is not
      always benign, as it can progress towards dementia and they may be two different
      entities. CONCLUSIONS: Early detection of memory disorder is important, since it
      is a common early sign of dementia syndromes. Its relatively straightforward
      diagnosis means that it can be used as an effective tool in the hands of general
      practitioners for the monitoring and treatment of the elderly in their
      communities.

PMID- 14730494
TI  - [Diagnosis of Parkinson's disease].
AB  - INTRODUCTION: Presently article carried out an up-to-date revision of the
      literature on the diagnosis of the Parkinson's disease, considering the clinical
      aspects, those of neuroradiology and the genetic diagnosis. DEVELOPMENT: The
      Parkinson's disease is the second most common neurodegenerative disorder and
      despite of the important development that has taken place in the last years as
      much in molecular genetics and neuroradiology, the diagnosis of this disease
      continuous being eminently clinical, the appropriate knowledge of the calls
      'cardinal signs' and its application in the diagnosis increases the possibility
      that this it is guessed right, regrettably the definitive approach is only
      obtained in the autopsy. The genetic studies and of neuroradiology mainly are
      presented as tools for a more reliable differential diagnosis with other
      parkinsonism forms and the knowledge of these techniques can be useful in the
      taking of therapeutic decisions or of the affected patient's integral treatment.
      They have also been different monogenic forms in origin to the sporadic form of
      the illness. CONCLUSION: The knowledge and search of the preponderant clinical
      signs increases the capacity of diagnostic of the illness, in the same way the
      appropriate use of additional methods of investigation, mainly in the
      differential diagnosis.

PMID- 14730495
TI  - [Neurophysiological monitoring in spine surgery. Spinal cord stimulation].
AB  - INTRODUCTION: Neurophysiological monitoring in spine surgery can be performed by
      a number of methods, although there is no general agreement about which is the
      best. AIM: The aim of this study was to evaluate our experiences using the method
      of spinal cord stimulation with recording carried out on the peripheral nerve.
      PATIENTS AND METHODS: We studied 51 patients with scoliosis who were submitted to
      surgical correction. Stimuli were administered with the cathode located in the
      dorsal epidural space, two levels above the curve to be corrected, and recording
      was performed on the posterior tibial nerve in the popliteal fossa. RESULTS:
      Potential was obtained in 78% of cases, with a very low number of averages and
      the maximum reduction in the amplitude of the potential was found to be 33%.
      Spinal cord stimulation evokes muscular responses in several muscles and sensory
      responses in the sural nerve. None of the patients who were monitored using this
      method presented postoperative neurological deficits added to their previous
      pathology. CONCLUSIONS: The neurogenic potentials obtained by epidural spinal
      cord stimulation are very useful for monitoring spine surgery because they are
      very stable, they can be obtained quickly, they avoid the need to interfere with
      the anaesthetist's field and because, albeit to a small extent, they may contain
      information about motor pathways. The main drawback is that it is not always
      possible to place the electrode and that in 22% of cases we have not managed to
      obtain the motor component and we have therefore had to be cautious in evaluating
      it, since its disappearance would only give rise to a partial reduction in the
      potential.

PMID- 14730497
TI  - [Intraoperative monitoring of nerve roots in spinal surgery].
AB  - INTRODUCTION: The use of intraoperative monitoring to determine the functional
      integrity of the nervous system has grown steadily over the last 15 years. The
      development of new instrumentation systems in spinal surgery and a greater
      incidence of complications have led to the need to introduce new methods of
      monitoring. AIMS AND DEVELOPMENT: The purpose of this study is to analyse the
      neurophysiological techniques that are currently available and applied in order
      to prevent injury to nerve roots and the fibres of the cauda equina, to assess
      their indications and to determine their limitations, as well as the effects
      caused by anaesthesia.

PMID- 14730498
TI  - [Neurophysiology of the development and maturation of the peripheral nervous
      system].
AB  - INTRODUCTION: Peripheral nerve maturation accounts during fetal life and infancy
      and varies with age. Nerve conduction studies are an objective procedure to
      investigate the development of the motor and sensory nerves. METHOD: We present a
      review of peripheral nervous system maturation studies in infancy, including our
      normal control group of infants from 1 week to 6 years of age. Motor and sensory
      nerve conduction velocity at birth is about one-half that of the normal adults,
      increases very quickly during the first year of life and reaches adult values
      between 3 and 5 years of age. All these electrophysiologic changes parallel the
      increase in numbers of large myelinated fibres throughout infancy. CONCLUSIONS:
      Nerve conduction studies are an accurate and non-invasive method of evaluating
      the peripheral nerve maturation in paediatric population when motor and sensory
      functions are particularly difficult to assess clinically.

PMID- 14730500
TI  - Abstracts of the 31th Meeting of the European Society of Pediatric Neurology. 27
      30 November 2003.

PMID- 14730499
TI  - [Neurology in the works of Lope de Vega].
AB  - The Madrilenian Felix Lope de Vega Carpio (1562 1635) was the first Spanish
      playwright. As a privileged witness to his time and with an exquisite knowledge
      of the human soul, he managed to portray all the social and human reality of the
      Golden Age in his more than 700 plays. Illnesses and those who suffer them are to
      be found throughout his works. Many neurological diseases, such as apoplexy,
      melancholy, headaches or epilepsy, appear quite often in his plays. His
      descriptions are accurate and the ideas about each disease reflect the knowledge
      that existed during his time (galenic, medieval or renaissance).

PMID- 14730502
TI  - [Fluoxetine-induced dystonia].

PMID- 14730503
TI  - Introduction. Renal osteodystrophy.

PMID- 14730504
TI  - Parathyroid hormone: new assays, new receptors.
AB  - Accurate measurements of parathyroid hormone (PTH) in plasma are necessary for
      the assessment, monitoring, and therapy of disorders of bone and mineral
      metabolism including renal osteodystrophy. Assays for PTH have evolved to provide
      2-site immunometric assays that are highly specific for the intact 84 amino-acid
      peptide, PTH (1-84). With the advent of such assays, it has been shown that the
      prior generation of assays, thought to measure intact PTH, in fact, also detected
      a PTH peptide that was truncated at the N-terminus and that appeared to be
      similar to PTH (7-84). There has been renewed interest in such circulating PTH
      fragments in view of the demonstration that PTH (7-84) (and other PTH peptides)
      might have biologic effects. These effects include an action to oppose the
      calcemic effect of PTH in vivo and to inhibit bone resorption and osteoclast
      generation in vitro. These effects appear to be mediated by actions of a receptor
      for PTH peptides with specificity for the C-terminal region of PTH and distinct
      from the PTH receptor known to be responsible for all of the classic actions of
      PTH. Although the C-PTH receptor has not yet been cloned, the observations have
      opened a new field of research in parathyroid physiology. Clinical applications
      of the assay of such PTH fragments in relation to the amount of circulating PTH
      (1-84) concentrations are being sought actively as the new PTH assay methodology
      is applied to the clinical arena and as the biology of the C-PTH receptor and C
      terminal PTH fragments are investigated.

PMID- 14730505
TI  - Vitamin D receptor and analogs.
AB  - In chronic kidney disease (CKD), high circulating levels of parathyroid hormone
      (PTH) cause osteitis fibrosa, bone loss, and cardiovascular complications that
      increase morbidity and mortality. Impaired production of 1,25-dihydroxyvitamin D
      (calcitriol), the hormonal form of vitamin D, is a major contributor to the
      generation and maintenance of parathyroid hyperplasia and increased synthesis and
      secretion of PTH. Calcitriol inhibits PTH gene transcription and ameliorates
      parathyroid hyperplasia by suppressing the expression of and growth signals from
      the autocrine transforming growth factor alpha (TGFalpha)/epidermal growth factor
      receptor (EGFR)-growth loop, a main determinant of parathyroid cell
      proliferation. Calcitriol reduction of parathyroid hyperplasia and serum PTH
      levels demands a functional vitamin D receptor (VDR). Although VDR is normal in
      CKD, parathyroid VDR content is reduced markedly. Furthermore, VDR function, as a
      transcriptional regulator of vitamin D responsive genes, is impaired by several
      factors including hypocalcemia, hyperphosphatemia, accumulation of uremic toxins,
      and reduction in cellular levels of the VDR partner, retinoid X receptor. Therapy
      with calcitriol analogs can overcome the antagonism on calcitriol-VDR actions
      induced by CKD. Although not all analog formulations are equally effective, they
      offer a wider therapeutic window in counteracting vitamin D resistance and
      survival advantage over exclusive calcitriol therapy.

PMID- 14730506
TI  - Calcium-sensing receptors.
AB  - It is now known that variations in extracellular calcium concentration exert
      diverse physiologic effects in a variety of tissues that are mediated by a
      calcium-sensing receptor (CaSRs). In parathyroid tissue, the CaSR represents the
      molecular mechanism by which parathyroid cells detect changes in blood ionized
      calcium concentration, modulate parathyroid hormone (PTH) secretion accordingly,
      and thus maintain serum calcium levels within a narrow physiologic range. In the
      kidney, the CaSR regulates renal calcium excretion and influences the
      transepithelial movement of water and other electrolytes. More generally,
      activation of the CaSR represents an important signal transduction pathway in
      intestine, placenta, brain, and perhaps bone. Some of these actions involve cell
      cycle regulation, changes that may be relevant to understanding the pathogenesis
      of parathyroid gland hyperplasia in secondary hyperparathyroidism caused by
      chronic kidney disease. The CaSR represents an appealing target for therapeutic
      agents designed to modify parathyroid gland function in vivo, offering the
      prospect of novel therapies for selected disorders of bone and mineral
      metabolism. Other receptors capable of responding to extracellular calcium ions
      also have been identified, but the functional importance of these interactions
      remains to be determined.

PMID- 14730507
TI  - Kidney-bone, bone-kidney, and cell-cell communications in renal osteodystrophy.
AB  - The relationship between bone and the kidney in renal osteodystrophy is a complex
      interplay of kidney to bone connections, bone to kidney connections, and cell to
      cell connections. In addition, such interactions have a profound effect on the
      vasculature. In this review, we discuss the role of the bone morphogenetic
      proteins (BMPs) in the skeleton, kidney, and vasculature. In addition, we propose
      that deficiencies of these BMPs seen in chronic kidney disease (CKD) result in
      decreased bone remodeling and a compensatory secondary hyperparathyroidism (high
      turnover state). Treatment of the hyperparathyroidism blocks this compensatory
      arm and thus decreased bone remodeling occurs (low turnover). We review animal
      models of CKD in which treatment with BMP-7 resulted in normalization of both
      high and low turnover states. Finally, we discuss vascular calcification as it
      relates to bone metabolism. We discuss the roles of BMP-7 and 2 other bone
      regulatory proteins, osteoprotegerin (OPG) and alpha2-HS glycoprotein (AHSG,
      human fetuin), in the human vasculature and their implications for vascular
      calcification.

PMID- 14730508
TI  - Renal phosphate wasting disorders: clinical features and pathogenesis.
AB  - Rickets and osteomalacia are associated with hypophosphatemia in several disease
      states, including X-linked hypophosphatemic rickets, autosomal-dominant
      hypophosphatemic rickets, and tumor-induced osteomalacia. Recent advances in the
      understanding of these diseases include discovery of mutations in the genes
      encoding human phosphate-regulating gene with homologies to endopeptidases on the
      X chromosome (PHEX) and fibroblast growth factor 23 (FGF-23) and the finding of
      overproduction of FGF-23 and other proteins including matrix extracellular
      phosphoglycoprotein (MEPE) and frizzled-related protein 4 (FRP-4) in tumor
      induced osteomalacia. Research is ongoing to better define how these proteins
      relate to each other and to the sodium-phosphate cotransporter in both normal and
      abnormal phosphate metabolism. New and improved therapies for disorders of
      phosphate metabolism, osteomalacia, and rickets will develop as our knowledge of
      phosphate metabolism grows.

PMID- 14730509
TI  - Hypercalcemia of malignancy.
AB  - Less than 25 years ago tumor-induced hypercalcemia was often a lethal
      complication of cancer. Nowadays, it can be treated easily and successfully in at
      least 90% of cases by volume repletion in addition to the use of bisphosphonates
      that are potent anti-osteoclastic compounds. The standard therapy consists of the
      administration of 90 mg pamidronate or, more recently, 4 mg zoledronic acid, a
      more efficient bisphosphonate. When available, another alternative bisphosphonate
      is ibandronate. Recurrent hypercalcemia is nevertheless difficult to control and
      antibodies against parathyroid hormone-related protein could be useful for that
      matter in selected patients who are not in the terminal stage of their disease.
      Prevention of tumor-induced hypercalcemia is one of the objectives of long-term
      therapy with bisphosphonates in patients with tumor bone disease. The use of
      bisphosphonates in placebo-controlled trials has shown that the incidence of
      hypercalcemic episodes is reduced by more than one half.

PMID- 14730510
TI  - Inherited hypercalciuric syndromes: Dent's disease (CLC-5) and familial
      hypomagnesemia with hypercalciuria (paracellin-1).
AB  - Dent's disease and familial hypomagnesemia with hypercalciuria and
      nephrocalcinosis (FHHNC) are inherited diseases in which hypercalciuria,
      nephrocalcinosis, and renal failure are prominent features. Dent's disease
      resembles a Fanconi syndrome, with impaired reabsorption in the proximal tubule;
      FHHNC, with urinary loss of magnesium and calcium, is associated with impaired
      cation transport in the thick ascending limb of Henle's loop. Gene mapping in
      families and positional cloning led in both cases to identification of the
      responsible gene. Dent's disease is associated with mutations that disrupt
      function of a voltage-gated chloride channel, CLC-5, expressed in subapical
      endosomes of the proximal tubule and in other nephron segments. Impaired function
      of this channel disturbs reabsorption of filtered proteins, as well as other
      transport functions of the proximal tubule, and leads, apparently indirectly, to
      hypercalciuria and renal failure. FHHNC results from mutations in paracellin-1, a
      tight-junction protein that appears to be important in conducting or regulating
      paracellular cation transport. Impaired function of paracellin-1 leads
      specifically to urinary losses of magnesium and calcium, but because
      transcellular transport is intact these patients do not have hypokalemia or salt
      wasting. Identification of both genes represent triumphs of a genetic approach to
      solving problems of pathophysiology.

PMID- 14730511
TI  - Vascular calcification in chronic kidney disease.
AB  - Dialysis patients have increased cardiovascular morbidity, mortality, and
      vascular calcification, and the latter appears to impact the former. Recent
      evidence indicates that vascular calcification is an active, cell-mediated
      process. Osteoblast differentiation factor Cbfa1 and several bone-associated
      proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen)
      are present in histologic sections of arteries obtained from patients with end
      stage renal disease (chronic kidney disease stage V [CKD-V]). This supports the
      theory that vascular smooth muscle cells can dedifferentiate or transform to
      osteoblast-like cells, possibly by up-regulation of Cbfa1. In in vitro
      experiments, addition of pooled serum from dialysis patients (versus normal
      healthy controls) accelerated mineralization and increased expression of Cbfa1,
      osteopontin, and alkaline phosphatase in cultured vascular smooth muscle cells.
      Clinically, the pathogenesis of vascular calcification is not completely
      understood, although increased levels of phosphorus and/or other potential uremic
      toxins may play an important role by transforming vascular smooth muscle cells
      into osteoblast-like cells. Presumably, once this process begins, increased serum
      calcium X phosphorus product, or calcium load from binders, accelerates this
      process. In addition, it is likely that circulating inhibitors of calcification
      are also important. Further understanding of the pathophysiology of vascular
      calcification is needed to intervene appropriately.

PMID- 14730512
TI  - Special aspects of renal osteodystrophy in children.
AB  - Renal osteodystrophy represents a spectrum of skeletal lesions that range from
      high-turnover to low-turnover bone disease. Similar factors are involved in the
      pathogenesis of renal osteodystrophy in adult and pediatric patients with chronic
      kidney disease (CKD). However, growth retardation and the development of bone
      deformities are specific complications that occurred in pediatric patients with
      CKD. Metabolic acidosis, renal osteodystrophy, malnutrition, and disturbances in
      the insulin growth factor (IGF)/growth hormone (GH) are among the main factors
      involved and they are discussed briefly in this article. In addition to
      disturbances in bone remodeling, longitudinal bone growth occurs at the growth
      plate cartilage by endochondral ossification. Although young rats with
      experimental CKD have growth retardation, the characteristics of the growth plate
      are markedly different between animals with severe secondary hyperparathyroidism
      and those with calcium-induced adynamic osteodystrophy. These disturbances may
      suggest potential molecular mechanisms by which endochondral bone formation may
      be altered in renal failure, consequently leading to growth retardation.

PMID- 14730513
TI  - Osteoporosis and chronic kidney disease.
AB  - Bone disease is heterogenous and highly prevalent among those with chronic kidney
      disease, stage V (CKD-V) patients. Although we know much regarding the risk
      factors and outcomes associated with renal osteodystrophy, less is known about
      osteoporosis in CKD-V. Factors that predict bone loss in the CKD-V population are
      similar to those in the general population and include female gender, Caucasian
      race, older age, chronic disease, and immobility. In addition, some studies
      suggest that chronic acidosis and renal osteodystrophy may also increase the risk
      for bone loss. Little is known about associated adverse outcomes or the impact of
      therapeutic interventions for osteoporosis. Although we know that the risk for
      hip fracture is high among CKD-V patients and that fracture is associated with an
      increased risk for death, the role that bone loss plays is largely unknown.
      Current recommendations suggest that risk-factor modification is the most
      appropriate course of treatment for CKD-V-associated osteoporosis.

PMID- 14730518
TI  - Seeing with new eyes.

PMID- 14730514
TI  - Bone disease after kidney transplantation.
AB  - Kidney transplantation is the optimal form of renal replacement therapy for many
      with end-stage kidney disease. However, kidney transplantation comes with a
      unique set of medical complications, important among them is bone disease.
      Posttransplant bone disorders are manifestations of pathologic processes
      occurring posttransplant that are superimposed on preexisting disorders of bone
      and mineral metabolism secondary to kidney failure and/or diabetes mellitus. As a
      consequence of early rapid bone loss, which is seen commonly within the first 3
      to 6 months of transplant, the fracture risk posttransplant increases and has
      been reported as high as 5% to 44%. Posttransplant fractures occur more commonly
      at peripheral than central sites. Patients with a history of diabetes mellitus
      are at particular risk for fracture. Parathyroid hormone (PTH) and osteocalcin
      levels generally decrease after transplantation. Alkaline phosphatase and urinary
      collagen cross-links are unpredictable. Bone histology varies. No single
      biomarker unequivocally distinguishes between the various bone disorders found on
      biopsy examination. Immunosuppression is a major cause of posttransplant bone
      disorders. Glucocorticoids lead to decreased bone formation whereas the
      calcineurin inhibitors appear to cause increased bone turnover. Evaluating and
      managing posttransplant bone disease is an integral part of posttransplant
      medical care.

PMID- 14730519
TI  - Postanesthesia care of the patient suffering from traumatic brain injury.
AB  - Each year 1.5 million people in the United States suffer a traumatic brain injury
      (TBI), and many of these patients require immediate surgery. TBI patients provide
      additional assessment and technological challenges for perianesthesia nursing
      care. A major goal of PACU nursing is the prevention of secondary head injury
      during the postanesthesia period.

PMID- 14730521
TI  - Detection of hyponatremia in the PACU.
AB  - Fluid and electrolyte management is an important part of PACU nursing care. Any
      alteration in fluid and electrolytes, especially in the vulnerable elderly
      population, can be catastrophic. An assessment of hyponatremia following
      transurethral resection of the prostate requires that the PACU nurse be diligent
      in discovering the etiology of unexpected mental status changes.

PMID- 14730520
TI  - Nesiritide therapy for acute heart failure.
AB  - Each year, more than 1 million hospitalizations are the result of heart failure.
      Acute exacerbations of heart failure can occur following routine surgical
      procedures. One of the newest pharmacological therapies for heart failure is
      nesiritide. The PACU nurse's vital role in the early recognition and early
      intervention of heart failure may include the administration of this agent.

PMID- 14730522
TI  - The patient with an implantable cardioverter defibrillator.
AB  - Electrophysiologic technology developed over the past 20 years has improved the
      life expectancy of patients who have survived sudden cardiac death events. Use of
      an implantable cardioverter defibrillator (ICD) continues to increase as more
      indications for the device are researched. Patients with ICDs will be cared for
      in the postanesthesia care unit following cardiac and noncardiac surgery and
      require PACU nurses to be knowledgeable about this advanced and changing
      technology as well as provide for emotional and psychological needs.

PMID- 14730524
TI  - Vasopressors used in the critical care setting.

PMID- 14730525
TI  - Off with her nails.

PMID- 14730526
TI  - New product review: temporal artery thermometry.

PMID- 14730527
TI  - Pain in the critically ill patient.

PMID- 14730529
TI  - The PACU as critical care unit.

PMID- 14730533
TI  - Guest editorial: Racial and ethnic disparities in kidney disease.

PMID- 14730534
TI  - Differences between blacks and whites in the incidence of end-stage renal disease
      and associated risk factors.
AB  - In the United States, the age-and-gender-adjusted incident rate of end-stage
      renal disease (ESRD) for blacks has been 4 times higher than that for whites. We
      analyzed patient information and medical services contained in the Medicare 5%
      random sample database. White (n = 977,436) and black (n = 77,800) Medicare
      enrollees who were at least 65 years old on January 1, 1997, were followed from
      1999 to 2001. Hierarchical Cox regression models were used to estimate the
      relative risk of ESRD for blacks (with reference to whites) after adjustment for
      age and gender, socioeconomic status, special health conditions (anemia, chronic
      obstructive pulmonary disease, cardiovascular disease), primary causal diseases
      of ESRD (eg, diabetes, hypertension), diabetes care and preventive care (eg,
      hemoglobin A1c or lipid testing), and physician visits for primary or specialty
      care. The relative risk of ESRD for blacks (with reference to whites) was 3.52
      (95% confidence interval [CI], 3.25-3.80) after adjustment for age and gender;
      2.90 (95% CI, 2.67-3.15) after adjustment for socioeconomic status and special
      health conditions; and 2.11 (95% CI, 1.94-2.30) after further adjustment for
      primary causal diseases of ESRD, diabetes care and preventive care, and physician
      visits. We conclude that a higher prevalence of primary causal diseases of ESRD
      and lower access to diabetes care, preventive care, and primary physician visits
      in blacks compared with whites partially accounts for the racial difference in
      the incidence of ESRD in the elderly Medicare population. Public health policy
      should focus on improving access to care, which may lower the burden of ESRD in
      minority and other at-risk populations.

PMID- 14730535
TI  - Relationships of race and ethnicity to progression of kidney dysfunction and
      clinical outcomes in patients with chronic kidney failure.
AB  - In the United States, the incidence of end-stage renal disease (ESRD) is much
      higher for blacks, Native Americans, and Asians than for whites. The incidence of
      kidney disease is also higher for populations of Hispanic ethnicity. ESRD
      attributed to diabetes (ESRD-DM), hypertension (ESRD-HT), and glomerulonephritis
      (ESRD-GN), in this order of frequency, are the major categories of ESRD in the
      United States for all race/ethnic groups. By using the incidence rates of ESRD,
      during the period from 1997 through 2000, and with whites as reference, the
      highest rate ratio (RR) was observed for ESRD-HT in blacks (RR = 5.96), ESRD-DM
      in Native Americans (RR = 5.11), and ESRD-GN in Asians (RR=2.20). The data
      suggest that the excess of ESRD observed for racial/ethnic minorities may be
      reduced by interventions aimed at prevention/control of hypertension and
      diabetes. The data suggest that before developing ESRD, patients with chronic
      renal failure from minority groups have to face more barriers to receive high
      quality health care. This may explain why they see nephrologists later and are
      less likely to receive renal transplantation at initiation of renal replacement
      therapy (RRT). Improvements in quality of care after initiating RRT may explain
      the lower mortality and higher scores in heath-related quality of life observed
      for patients from racial/ethnic minorities.

PMID- 14730536
TI  - Pharmacological strategies for kidney function preservation: are there
      differences by ethnicity?
AB  - The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic
      groups. This is because of the increased prevalence of obesity, diabetes
      mellitus, the metabolic syndrome, and the inadequate control of elevated blood
      pressure and other cardiovascular-renal risk factors, especially in ethnic
      minority populations. The implications of the aforementioned trends in risk
      factor prevalence and control are profound. Moreover, these trends negatively
      impact patient quality of life and place an enormous financial burden on the
      health care system for the provision of care to patients with CKD, end-stage
      renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost
      importance to devise strategies that prevent kidney disease and delay progressive
      loss of kidney function in persons with CKD. Proven strategies include
      pharmacological interventions that lower blood pressure to less than target
      levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and
      reducing urinary protein excretion. It is also possible, although yet unproven,
      that correction of anemia and aggressive treatment of dyslipidemia may forestall
      the loss of kidney function. In general, ethnic minorities are underrepresented
      in most large trials. Recently, a few outcome clinical trials in blacks have
      reinforced the lessons of kidney function preservation already learned in
      nonblack populations. That is, the reversible risk factors for CKD appear to be
      virtually identical and, at least in nondiabetic CKD, pharmacological targeting
      of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting
      enzyme inhibitors and angiotensin II receptor blockers preserves kidney function
      better than non-RAAS blood pressure-lowering regimens, especially when
      significant proteinuria exists. Although more CKD studies in ethnic minorities
      are needed, until they become available, the best available evidence from the
      existing clinical trial database should be applied to minorities with CKD-even
      when specific data are not available for a specific racial or ethnic group. Why
      this approach? First, there are no known unique risk factors for kidney disease
      in any ethnic group. Second, poor control of reversible risk factors for CKD is
      universal, particularly in blacks and other ethnic minorities. Thus, it is
      logical to predict that more efficient use of strategies proven to forestall loss
      of kidney function will reduce the excess of CKD and ESRD in ethnic minorities
      relative to non-minority populations. However, medical-based strategies alone are
      probably not enough. The global epidemic of obesity will fuel the growing
      population of persons, especially among ethnic minorities, with diabetes, the
      main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely
      to abate without innovative and ultimately effective public health approaches.

PMID- 14730537
TI  - Is obesity a major cause of chronic kidney disease?
AB  - Excess weight gain is a major risk factor for essential hypertension and for end
      stage renal disease (ESRD). Obesity raises blood pressure by increasing renal
      tubular sodium reabsorption, impairing pressure natriuresis, and causing volume
      expansion because of activation of the sympathetic nervous system and renin
      angiotensin system and by physical compression of the kidneys, especially when
      visceral obesity is present. Obesity also causes renal vasodilation and
      glomerular hyperfiltration that initially serve as compensatory mechanisms to
      maintain sodium balance in the face of increased tubular reabsorption. In the
      long-term, however, these changes, along with the increased systemic arterial
      pressure, create a hemodynamic burden on the kidneys that causes glomerular
      injury. With prolonged obesity, there is increasing urinary protein excretion and
      gradual loss of nephron function that worsens with time and exacerbates
      hypertension. With the worsening of metabolic disturbances and the development of
      type II diabetes in some obese patients, kidney disease progresses much more
      rapidly. Weight reduction is an essential first step in the management of
      obesity, hypertension, and kidney disease. Special considerations for the obese
      patient, in addition to adequately controlling the blood pressure, include
      correction of the metabolic abnormalities and protection of the kidneys from
      further injury.

PMID- 14730538
TI  - Ethical implications of ethnic disparities in chronic kidney disease and kidney
      transplantation.
AB  - Chronic kidney disease (CKD) is a major epidemic in underserved and minority
      populations largely due to excess rates of hypertensive and diabetic kidney
      disease. Multiple complex socioeconomic barriers to early diagnosis and optimal
      therapies as well as delayed referral for kidney transplantation have created
      disparities in CKD care provided to ethnic minorities. Disparities exist in wait
      list time and kidney transplant rates for Native Americans and blacks,
      independent of insurance status. Moreover, independent of genetic matching, long
      term transplant outcomes in blacks remain significantly lower than all other
      ethnic groups, suggesting that poorly understood social factors contribute to
      these survival differences. The existence of these disparities raises ethical
      concerns of equity and social justice in terms of the allocation of scarce
      resources. Although current changes in allocation policies will improve some
      disparities, more efforts are ultimately needed to improve access to care and the
      overall health and survival for all individuals at risk for CKD, independent of
      their race, ethnicity, or socioeconomic status.

PMID- 14730539
TI  - Research opportunities for reducing racial disparities in kidney disease.
AB  - Several minority populations in the United States have higher risks for end-stage
      renal disease than does the white population. This article addresses some areas
      for research aimed at reducing the disproportionate risks. Four general areas are
      considered: health services, risk factors and causative agents, clinical trials,
      and awareness campaigns.

PMID- 14730540
TI  - Translating research findings of chronic kidney disease management to clinical
      practice: Challenges and opportunities.
AB  - Chronic Kidney disease (CKD) has been identified as a public health epidemic,
      fueled in part by improved outcomes of both diabetic and cardiac patient
      populations, as well as by the increasing recognition that it is possible to
      identify CKD at earlier stages. The estimated 8 to 10 million Americans that have
      CKD, with its concomitant morbidity and mortality, have the potential to
      overwhelm the current system of specialty practice medicine and health care
      resources. How can clinicians, clinician scientists, and health care
      administrators translate research findings into clinical practice in an effective
      manner to improve the care of this burgeoning patient group? The challenge of
      translating research into clinical care requires identification of that which we
      do and do not know, communication of knowledge between those who do and do not
      know, and efficient collection of information for systematic evaluation. This
      article will describe the challenges of translating current research findings
      into clinical practice. There is a need to identify the complexity of CKD disease
      processes and issues associated with delivery of care and to describe the
      difficulties in the dissemination of new knowledge to physicians. Because of the
      propensity of CKD to affect identifiable groups of patients, we will discuss the
      potential challenges of these strategies given the racial, ethnic, and cultural
      diversity in North America. A potential solution to these challenges is a new
      paradigm of "process-based medicine" that integrates clinical and basic science
      research findings with multidisciplinary and shared care models of health care
      delivery. In this context, attention to advances in information technology, the
      cognitive processes that underlie physician learning, and the findings of outcome
      research may ensure true integration of clinical research and clinical practice.

PMID- 14730541
TI  - Genetic variation in the epithelial sodium channel: a risk factor for
      hypertension in people of African origin.
AB  - High blood pressure occurs commonly in individuals of African origin, leading to
      an increased risk of cardiovascular and end-stage renal disease (ESRD). Black
      individuals frequently have low plasma renin activity, and their blood pressure
      responds well to salt reduction, suggesting that abnormalities in renal sodium
      handling may be important in the etiology of hypertension in this population. The
      epithelial sodium channel (ENaC) has a central role in sodium transport across
      membranes, and in the kidney it contributes to the regulation of blood pressure
      via changes in sodium balance and blood volume. Rare monogenetic disorders have
      been described in association with hypertension, such as Liddle's syndrome. In
      addition, other ENaC polymorphisms have also been described, some of which are
      more common in black individuals. The T594M polymorphism of ENaC occurs
      exclusively in black individuals and is associated with hypertension in a black
      South London population. There is preliminary evidence that amiloride is
      effective as monotherapy in hypertensives with the T594M polymorphism, and a
      further study is underway to determine whether this is indeed a safe and specific
      treatment. If so, then amiloride may provide an important new strategy for blood
      pressure control in affected black hypertensives.

PMID- 14730542
TI  - Diversity and patient care in a shrinking world.
AB  - The purpose of this article is to discuss current standards for preparing nurses
      to practice as culturally competent generalists in our rapidly shrinking world.
      Culturally competent care, transcultural nursing practice, and the nursing
      professions' standards of nursing care for diverse populations are applied to
      nursing education, renal nursing, and transplant nursing issues. Recommendations
      for breaking down health care gaps and barriers include ensuring, within the
      boundaries and control base of our own practice, that cultural, racial, economic,
      spiritual, and social diversity is respected and acknowledged.

PMID- 14730543
TI  - Literature review and implications for social work practice with Hispanic
      dialysis patients.
AB  - Many renal social workers are uncertain about what to expect when providing
      services to Hispanic patients. The Hispanic dialysis population is a growing
      minority with a diverse culture. The Hispanic patient's family members are a
      source of natural support and strength. This article profiles a review of the
      literature available regarding working with Hispanic patients and their families
      in a medical setting and provides implications for renal social work practice.

PMID- 14730544
TI  - Incorporating ethnic and cultural food preferences in the renal diet.
AB  - Medical nutrition therapy (MNT), nutrition education, and counseling are
      essential components for effective management of end-stage kidney disease (ESKD).
      Patients with ESKD have to alter their diets and to implement new eating
      behaviors, sometimes irrespective of ethnic and cultural food preferences because
      of their high content of specific nutrients. Ethnic and cultural factors
      influence dietary adherence. Therefore, assessing cultural issues surrounding
      food and food preferences may help improve dietary adherence. A large percentage
      of the ESKD population in the United States is black and Hispanic, with cultural
      food preferences that are particularly high in potassium, phosphorus, and sodium.
      This article provides an overview of the role of culture and ethnicity in food
      habits and dietary adherence, a list of cultural and ethnic foods that should be
      examined and incorporated in the development of an appropriate renal diet meal
      plan for black and Hispanic Americans with ESKD, and practical recommendations
      for cross-cultural nutrition counseling. If MNT is to be effective in the medical
      management of patients from different cultural and ethnic backgrounds, it must
      incorporate more traditional and customary foods in the renal diet meal plan.

PMID- 14730545
TI  - Racial and ethnic differences in the incidence and progression of focal segmental
      glomerulosclerosis in children.
AB  - Idiopathic focal segmental glomerulosclerosis (FSGS) is a common cause of
      nephrotic syndrome in pediatric and adult patients. Most children with FSGS do
      not respond to any form of therapy and progress to end-stage renal disease
      (ESRD). FSGS reoccurs in the transplanted kidney in approximately one third of
      initial transplants and in a substantially higher percentage of subsequent
      transplants once FSGS has recurred in an earlier transplant. Thus, FSGS is a
      disease with substantial morbidity. Over the past several years, the incidence of
      FSGS in adults and children appears to be increasing, particularly in certain
      racial groups and ethnic populations. Several recent studies in adult and
      pediatric patients suggest that the incidence of FSGS is increasing particularly
      in the black population. In addition, some studies have also demonstrated a more
      rapid progression of FSGS to ESRD in black patients compared to other ethnic
      groups. Racial and ethnic background is likely to have a substantial influence on
      the incidence and progression of FSGS in children and adults. It is likely that
      specific genes or a combination of genes influence the different clinical
      manifestations of FSGS in racial and ethnic groups. Genetic mutations in NPHS1
      gene, which encodes nephrin, have been found to cause congenital nephrotic
      syndrome. Genetic mutations in the NPHS2 gene, which encodes podocin, recently
      have been shown to be strongly associated with a recessive form of steroid
      resistant nephrotic syndrome. Mutations in the ACTN4 gene that encodes actinin 4
      has also been associated with familial nephrotic syndrome. A role for ACE
      polymorphisms in the progression of FSGS has been found in some studies. Future
      investigations to identify polymorphisms that influence the development of FSGS,
      the progression of FSGS, and the response to therapy will greatly improve
      understanding of the pathogenesis and management of FSGS.

PMID- 14730546
TI  - Needed: a catalyst for change.

PMID- 14730550
TI  - Reference distributions for complement proteins C3 and C4: a practical, simple
      and clinically relevant approach in a large cohort.
AB  - The two serum proteins of the complement cascade in the highest concentrations,
      C3 and C4, respond to various conditions in much the same manner as do other
      positive acute-phase proteins. A major difference is that they are relatively
      sluggish in response to cytokine drive, requiring several days rather than hours
      to be detectably elevated by serial measurements. As with other acute-phase
      proteins, there are many processes that up- or down-regulate synthesis, including
      infection or inflammation, hepatic failure, and immune-complex formation.
      Clinicians may find it difficult to distinguish among these processes, because
      they often occur simultaneously. The situation is further complicated by genetic
      polymorphism, with rare instances of markedly reduced synthesis and circulating
      levels, and consequent vulnerability to infection. C3 and C4 are measured for
      clinical purposes to help define certain rheumatic and immunologically mediated
      renal diseases. Interpreting the measured blood levels of these two components
      requires one to consider the intensity of the inflammatory drive, the timing of
      the suspected clinical process, the production of complement-consuming immune
      complexes, and the possible existence of benign circumstances. In this fifth
      article in a series, reference ranges for serum levels of two complement proteins
      (C3 and C4) are examined. The study is based on a cohort of over 55,000 Caucasian
      individuals from northern New England, who were tested in our laboratory in 1994
      1999. Measurements were standardized against certified reference material (CRM)
      470/reference preparation for proteins in human serum (RPPHS), and analyzed using
      a previously described statistical approach. Individuals with unequivocal
      laboratory evidence of inflammation (C-reactive protein of 10 mg/L or higher)
      were excluded. Our results show that the levels of C3 and C4 change little during
      life and between the sexes, except that they increase slightly and then fall
      after age 20 in males and at about age 45 in females. When values were expressed
      as multiples of the age- and gender-specific median levels, the resulting
      distributions fitted a log-Gaussian distribution well over a broad range. When
      patient data are normalized in this manner, the distribution parameters can be
      used to assign a centile corresponding to an individual's measurement, thus
      simplifying interpretation.

PMID- 14730551
TI  - Reference distributions for complement proteins C3 and C4: a comparison of a
      large cohort to the world's literature.
AB  - The lack of credible reference materials and satisfactory methods for quantifying
      serum levels has limited the bedside use of complement protein (C3 and C4)
      measurements. However, great technological strides have been made in the last few
      years. The remaining barrier to a more relevant and cost-effective use of serum
      protein data for diagnosis and prognosis is the availability of reliable
      reference intervals from birth to old age for both males and females. Fifty-one
      publications reporting reference intervals were identified that meet the criteria
      used in our prior four studies, and these were analyzed statistically. Previous
      small studies with constrained age ranges agree, on average, with our larger
      series of life-long reference ranges. This meta-analysis provides support for our
      reference ranges and places them in the context of previous publications.

PMID- 14730552
TI  - Relationship between levels of urinary type IV collagen and renal injuries in
      patients with IgA nephropathy.
AB  - Because type IV collagen is synthesized by podocytes and mesangial cells, we
      investigated the relationship between levels of urinary type IV collagen (uIV)
      and renal injuries in patients with IgA nephropathy. uIV was measured by a highly
      sensitive one-step sandwich enzyme immunoassay prior to renal biopsy. Patients
      with IgA nephropathy were classified into four grades (grade 1 = good prognosis,
      grade 2 = relatively good prognosis, grade 3 = relatively poor prognosis, and
      grade 4 = poor prognosis) by the prognostic criteria of the Ministry of Health,
      Labor, and Welfare of Japan. Levels of uIV in grade 4 were significantly higher
      than those in grades 1-3. These levels tended to increase gradually due to
      progression of renal injuries. The grades were further divided into two groups:
      group I (good or relatively good prognoses) and group II (relatively poor or poor
      prognoses). Patients with proteinuria of <1.0 g/day were defined as groups Ip and
      IIp. The levels of uIV in group II were significantly higher than those in group
      I, and those in group IIp were significantly higher than those in group Ip. It
      appears that the level of uIV can be a useful marker for detection of renal
      injuries in IgA nephropathy.

PMID- 14730553
TI  - Methods to detect antifibrillarin antibodies in patients with systemic sclerosis
      (SSc): a comparison.
AB  - Autoantibodies against nucleolar antigens are common in systemic sclerosis (SSc).
      They include autoantibodies against fibrillarin (Fb), which are serological
      markers for SSc. Fb is associated with the evolutionally-conserved box C/D of
      small nucleolar RNAs (snoRNAs). We compared indirect immunofluorescence (IIF),
      Western blot (WB), and immunoprecipitation (IPP) of total small RNAs assays to
      determine which of these techniques is most specific for the detection of
      snoRNPs. We also examined the frequency and specificity of autoantibodies from
      SSc patients to snoRNAs, snRNAs, and scRNAs, and concluded that 1) IIF can not
      determine autoantibody specificity against Fb, 2) 36% of SSc sera were false
      negative by WB, and 3) by IPP, anti-Fb autoantibodies from SSc patients can bind
      U3, U8, U13, U15, and U22 snoRNAs.

PMID- 14730554
TI  - Measurement of cytotoxic activity in experimental cancer.
AB  - Several tumor cell systems have been developed for investigating the cytotoxic
      activity of different substances. The Ehrlich ascytic tumor (EAT) has been
      studied extensively and used to increase our comprehension of immunotherapy
      (Yamamoto and Naraparaju. Cancer Res 57:2187-2192, 1997). In this study, we
      evaluated the ability of an enzymatic method to assess cytotoxic tumor activity
      in vitro. To prepare cytotoxic cells, lymphoid cells isolated from the lymph
      nodes of C57BL/6 mice were activated with interleukin-2 (IL-2). The cytotoxic
      activity to EAT cells was assessed by an enzymatic test using lactate
      dehydrogenase (LDH), an enzyme widely distributed in mammalian tissues which, in
      the presence of NAD/NADH, converts lactate to pyruvate. IL-2 treatment of lymph
      node cells induced a greater percentage of lysis (75.47%) than effector cells
      that were not treated with IL-2 (42.38%). This suggests that IL-2 directly
      activates effector cells and not tumor cells. The results demonstrate that the
      LDH release-measurement method can be utilized to assay cytotoxic cell-mediated
      activity in which murine tumor cells act as the target. Levels of IL-2 appear to
      have a direct correlation to cellular immunity and treatment with these
      substances may strengthen immune function and decrease the pace of disease
      development.

PMID- 14730555
TI  - Serum cystatin C assay for the detection of early renal impairment in diabetic
      patients.
AB  - The ability to assess renal function in diabetes patients rapidly and early is of
      major importance. This study was designed to determine whether cystatin C can
      replace serum creatinine as the screening marker for reduced glomerular
      filtration rate (GFR) in type 2 diabetes patients. The study was performed on 51
      type 2 diabetic patients. GFR was estimated by the plasma clearance of (99m)Tc
      DTPA. The correlation between (99m)Tc-DTPA clearance and levels of serum cystatin
      C, serum creatinine, and creatinine clearance was determined. Sensitivity and
      specificity for the diagnosis of renal impairment (defined as GFR<68 ml/min) were
      calculated by a receiver operating characteristic (ROC) curve for serum cystatin
      C, serum creatinine, and creatinine clearance. The correlation coefficients with
      (99m)Tc-DTPA clearance were -0.744 for serum cystatin C, -0.658 for serum
      creatinine, and +0.625 for creatinine clearance (P<0.001). With a cutoff value of
      68 mL/min, the area under the ROC curve (AUC) was 0.891 for cystatin C, 0.77 for
      creatinine, and 0.753 for creatinine clearance. The AUC was statistically
      different between serum cystatin C and creatinine clearance (P<0.05). The ROC
      plot indicates that cystatin C is superior to serum creatinine and creatinine
      clearance for detecting impaired GFR. Serum cystatin C appropriately reflects GFR
      in diabetes, and is more efficacious than serum creatinine and creatinine
      clearance in detecting reduced GFR in type 2 diabetes patients.

PMID- 14730556
TI  - Flow cytometric study of neutrophilic granulopoiesis in normal bone marrow using
      an expanded panel of antibodies: correlation with morphologic assessments.
AB  - Flow cytometry studies of surface markers of neutrophils have been performed
      mostly on peripheral blood, and for a limited spectrum of diseases. Studying
      maturation defects on developing neutrophils in the bone marrow (BM) may be
      helpful in BM diseases, such as myelodysplastic syndromes and Shwachman-Diamond
      syndrome. We applied an expanded panel of antibodies to examine normal maturation
      patterns in 26 control samples of BM together with microscopic correlation.
      Promyelocytes correlated well with the CD24(-) and CD11b(-) populations, and
      metamyelocytes correlated well with the CD16(+) population (intermediate
      positivity). An excellent correlation was also identified between the sum of
      bands and segmented neutrophils and each of the following: CD16(++) (strong
      positivity), CD35(+), CD87(+), and CD64(-). Although visually identified
      segmented neutrophils paralleled CD10 positivity, there was an appreciable
      difference between both methods. We conclude that neutrophilic granulocyte
      maturation in the BM is accompanied by a change in surface antigens that reflects
      certain stages of development. A successful strategy for detecting maturation
      defects is to include several antibodies that are known to be expressed or absent
      at the same stage of maturation, such as CD16, CD35, CD64, and CD87.

PMID- 14730557
TI  - Overestimation of HDL-cholesterol using a homogeneous "direct" assay.
AB  - Direct HDL-cholesterol (HDLc) assays have several advantages over other assays
      that are more laborious and time-consuming. A recent College of American
      Pathologists (CAP) report indicates that at least 385 Beckman LX-20 analyzers use
      the selective detergent (homogeneous or direct) method for analyzing HDLc. There
      is no published evaluation of direct HDLc assays on the Beckman platform. Here we
      report our evaluation of a direct HDLc assay marketed by Beckman for the Beckman
      LX-20 analyzers. In general, the assay performed well; however, the total error
      was not within National Cholesterol Education Program (NCEP) guidelines. This was
      largely because of a significant positive bias that appeared to be due, at least
      in part, to triglycerides. This bias was worse at HDLc concentrations <40 mg/dL,
      which may make it difficult to identify a low HDLc concentration and consequently
      an increased risk for cardiovascular disease (CVD).

PMID- 14730558
TI  - Antioxidant capacities of ascorbic acid, uric acid, alpha-tocopherol, and
      bilirubin can be measured in the presence of another antioxidant, serum albumin.
AB  - Human serum contains several antioxidants. The total antioxidant capacity (AOC)
      is the sum of all the antioxidant activities present in serum. The aim of our
      study was to investigate whether the AOC of bilirubin (BR), alpha-tocopherol
      (TOH), ascorbic acid (AA), and uric acid (UA) could be measured with good
      precision and recovery in the presence of human serum albumin (HSA). We measured
      the AOC of each antioxidant using a Cobas Mira S instrument (Roche Diagnostic
      Systems, Montclair, NJ) by measuring the inhibitory effect of a given compound on
      the oxidation of the radical cations of 2,2'-azino-di-(3-ethylbenzthiazoline 6
      sulphonate) (ABTS) incubated with metmyoglobin and H(2)O(2). The assay had a
      linear AOC response range of 27-2,000 micromol/L. The within- and between-day
      coefficients of variation (CVs) did not exceed 3.4% and 4.2%, respectively. The
      AOC of albumin in serum is much greater than that of BR, TOH, AA, or UA owing to
      the substantially greater concentration of HSA in serum. An aliquot of a solution
      of AA, UA, BR, or TOH was added to HSA or distilled water, and the AOC was
      determined. The AOC of BR, TOH, AA, and UA increased in a linear way with
      increasing concentrations. However, we found that the magnitude of increase in
      the AOC of a mixture of HSA and any of these antioxidants was lower than the sum
      of the AOC of HSA and any one of the following: AA, UA, BR, or TOH (all expressed
      in micromol/L).

PMID- 14730559
TI  - Improved method for molecular diagnosis of myotonic dystrophy type 1 (DM1).
AB  - Myotonic dystrophy type 1 (DM1) has been identified as the amplification of a
      polymorphic (CTG)n repeat in the 3' untranslated region of a gene encoding a
      serine/threonine kinase (DMPK). The length of the CTG repeat correlates with
      clinical severity and the age at onset of the disease. Thus, the ability to
      perform quick and accurate molecular genetic diagnoses is of great importance to
      patients and their families. Polymerase chain reaction (PCR) and Southern blots
      are essential methods for such diagnoses. All previously published methods are
      based on Southern blots using radioactive probes. Furthermore, the enzymes used
      for DNA digestion result in larger fragments, which makes it difficult to
      accurately determine the insert sizes. In this study, we report an improved
      method for molecular diagnosis of DM1. This method employs an initial screening
      with PCR followed by Southern blots using nonradioactive probes and TaqI as the
      enzyme, and provides a much better resolution of the labeled bands.

PMID- 14730560
TI  - Commentary: clinical diagnostic use of cystatin C.
AB  - Clinicians recognize and compensate for limitations in estimating the glomerular
      filtration rate (GFR) using serum creatinine (sCr) measurements by the use of
      timed collections and mathematical manipulations of sCr. These limitations stem
      from that fact that sCr is affected by nonrenal influences, including muscle mass
      and disease state. In addition, sCr may not be sensitive enough to detect minimal
      declines in GFR in those patient populations in which it is important to
      recognize early decline. This brief review describes the limitations of sCr, and
      examines the contribution that sCysC may be able to make in the early recognition
      of declining renal function. The physiology of CysC is presented, as are the
      results of clinical investigations that suggest sCysC is in many instances
      superior to sCr in the recognition of early decline in renal function. Certain
      exceptions to this are noted.

PMID- 14730561
TI  - A systematic investigation into the recovery of radioactively labeled proteins
      from sodium dodecyl sulfate-polyacrylamide gels.
AB  - We report the results of a systematic investigation designed to optimize a method
      for quantifying radioactivity in proteins in sodium dodecyl sulfate
      polyacrylamide gels. The method involves dissolving appropriately sized pieces of
      gel in hydrogen peroxide and heating to 70 degrees C overnight followed by liquid
      scintillation counting. H(2)O(2) had no effect on the count rates of
      [(14)C]bovine serum albumin (BSA) when counted in a conventional liquid
      scintillation system, and the count rates remained stable for several days.
      Temperatures below 70 degrees C resulted in incomplete extraction of
      radioactivity from gels containing [(14)C]BSA, but there was also a significant
      reduction in count rates in samples incubated at 80 degrees C. At 70 degrees C
      recovery was not affected by the amount of sample loaded onto the gel or by the
      staining procedure (Coomassie Brilliant Blue or SYPRO Ruby). Recoveries were in
      the range of 89-94%, and the coefficient of variation for five replicate samples
      was 5-10%. This method offers a reliable way of measuring the amount of
      radioactivity in proteins that have been separated by electrophoresis. It may be
      useful, for example, in quantitative metabolic labeling experiments when it is
      necessary to know precisely how much tracer has been incorporated into a
      particular protein.

PMID- 14730562
TI  - Resolution of 8-aminonaphthalene-1,3,6-trisulfonic acid-labeled glucose oligomers
      in polyacrylamide gel electrophoresis at low gel concentration.
AB  - A discontinuous Tris-Cl/acetate (OAc) buffer system, unprecedently containing OAc
      as the trailing constituent, and operative in polyacrylamide gel electrophoresis
      (PAGE) at low polyacrylamide concentration (T = 4.8%) is described in the paper.
      The characteristics of the electrophoretic system are illustrated by the
      resolution of fluorescent 8-aminonaphthalene-1,3,6-trisulfonic acid (ANTS)
      labeled malto-oligosaccharides and dextran homopolymers. In this buffer system,
      the resolving phase is constituted by Tris-OAc behind a moving boundary formed
      between the leading chloride ion of Tris-HCl gel buffer and the trailing OAc ion
      provided by a catholyte of NH(4)OAc. In contrast with the results obtained with
      Tris-CI/glycinate buffer commonly used in electrophoresis, or with Tris
      CI/borate, the best resolution of the glucose oligomers containing 1-4 glucose
      units in Tris-OAc, pH 8.8, ionic strength of 0.08, was obtained at 4.8%
      polyacrylamide concentration, using 0.5 M NH(4)OAc, pH 9.5 as the catholyte.
      Under those conditions, the ANTS-glucose oligomers were separated with mobilities
      decreasing from glucose to maltohexaose. The linear Ferguson plots (log relative
      mobility, R(f), vs.%T) of the glucose oligomers show that the surface net charge
      of those oligomers is inversely related to their sizes, given by the slopes,
      K(R), of the plots. The molecular weight of the oligomers is directly but
      nonlinearly related to K(R). The novel electrophoretic system illustrated here
      for separation of short ANTS-saccharides can be potentially applied to the
      resolution of other biomolecules such as rapidly migrating DNA, peptides or
      proteins.

PMID- 14730563
TI  - Analytical and preparative native polyacrylamide gel electrophoresis:
      Investigation of the recombinant and natural major grass pollen allergen Phl p 2.
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blot are amongst the most popular methods for allergen characterization, such as
      comparison of recombinant allergens with their natural counterparts. Native PAGE
      was evaluated as a possible robust and simple method offering high-resolution
      capacity for characterization of the major grass pollen allergen Phl p 2.
      Analytical separation of recombinant Phl p 2 provided a superior quality control
      in terms of homogeneity and, after Western blotting, immunoglobulin E (IgE)
      reactivity. Separation of natural Phl p 2 identified two major isoforms which
      were shown to have different N-terminal sequences and IgE-binding properties.
      After isolation using preparative native PAGE in combination with
      electrodialysis, both isoforms were investigated by specific proteolysis and
      reversed-phase high-performance liquid chromatography (RP-HPLC). The results
      demonstrate differences in the primary structures and that the recombinant
      counterpart corresponds exactly to one isoform. Analytical and preparative native
      PAGE thus proved to be powerful tools for the investigation of allergen isoforms
      and quality control of recombinant counterparts.

PMID- 14730564
TI  - Pyrosequencing trade mark technology at elevated temperature.
AB  - To date, the Pyrosequencing trade mark technology has been performed at 28
      degrees C due to the low thermostability of the firefly luciferase. In this
      study, firefly luciferase was stabilized in the presence of glycine betaine,
      allowing DNA sequencing at 37 degrees C. By increasing the temperature to 37
      degrees C, false signals due to primer-dimers and loop-structures were decreased
      significantly. In addition, a combination of (i) replacing the natural dGTP with
      7'deaza-dGTP in the polymerase chain reaction (PCR), (ii) 1.6 M glycine betaine,
      and (iii) an increase of the temperature to 37 degrees C enabled us to sequence a
      DNA template with the initial sequence 3'-ATGGCCCGGGGGGGAGCTCCA em leader 5'.
      Furthermore, we describe a method to analyze if a primer forms a primer-dimer
      with extendable 3'-ends.

PMID- 14730565
TI  - Quantitative and qualitative profiling of mitochondrial DNA length heteroplasmy.
AB  - Quantitative and qualitative analysis of mitochondrial DNA length heteroplasmy
      for the first hypervariable segment (HV1) and second hypervariable segment (HV2)
      regions were performed using size-based separation of fluorescently-labeled
      polymerase chain reaction (PCR) products by capillary electrophoresis. In this
      report, the relative proportions of length heteroplasmies in individuals were
      determined, and each length variant in the heteroplasmic mtDNA mixture was
      identified. The study demonstrated that 36% and 69% of Koreans show length
      heteroplasmy in the HV1 and HV2 regions, respectively. Electropherograms revealed
      that length heteroplasmy in the HV1 region resulted in over 5 length variants in
      an individual. The peak patterns of length heteroplasmy in the HV1 region were
      classified into five major types. In the HV2 region, length heteroplasmy resulted
      in 3-6 length variants in an individual, and showed seven variant peak patterns.
      The increased knowledge concerning mtDNA length heteroplasmy is believed to not
      only offer a useful means of determining genetic identity due to increased
      mitochondrial DNA haplotype diversity by allowing mtDNAs to be classified into
      several peak patterns, but also represent a promising tool for the diagnosis of
      several common diseases which are etiologically or prognostically associated with
      mtDNA polymorphisms.

PMID- 14730566
TI  - A flow injection-capillary electrophoresis system with high-voltage contactless
      conductivity detection for automated dual opposite end injection.
AB  - The system comprises two flow injection-capillary electrophoresis interfaces into
      which the opposite ends of the separation capillary are inserted. The electrolyte
      solution flows through both interfaces by use of hydrostatic pressure. The
      injection of the samples into the electrolyte flow is accomplished by a rotary
      type chromatographic valve at the grounded side and by a pinch-valve injector at
      the high-voltage side that provides sufficient isolation from the high electric
      field. The system allows a fully automated dual-injection sequence of samples
      from both capillary ends and simultaneous electrophoretic separation of anions
      and cations in the samples. The analytes are detected by a high-voltage
      contactless conductometric detector positioned approximately in the middle of the
      separation capillary. The parameters of the system were evaluated. The
      repeatability of the flow injection-capillary electrophoresis system for the
      simultaneous determination of anions and cations was evaluated for ten
      consecutive injections and relative standard deviation (RSD) values for peak
      areas were better than 1.0%. The sample throughput for total ionic analysis was
      estimated to be 25 samples per hour. The system was used for automated
      simultaneous analysis of anions and cations in various real samples. Using a
      short separation capillary, rapid total ionic analysis in less then 1 min is
      demonstrated.

PMID- 14730567
TI  - Feasibility of nonvolatile buffers in capillary electrophoresis-electrospray
      ionization-mass spectrometry of proteins.
AB  - The combination of capillary electrophoresis (CE) and electrospray ionization
      mass spectrometry (ESI-MS) via a triaxial interface was studied as a potential
      means for the characterization of intact proteins. To evaluate the possibility to
      use a nonvolatile electrolyte for CE, the effect of sodium phosphate and ammonium
      borate on the MS signal of the proteins insulin, myoglobin, and bovine serum
      albumin (BSA) was investigated by employing infusion experiments, and compared to
      the effect of ammonium formate and formic acid. The study shows that with formic
      acid (50 mM, pH 2.4) the most intense protein signals were obtained, while the
      use of sodium phosphate buffer (5 and 10 mM, pH 7.5) almost completely diminished
      the MS response. Ammonium formate and ammonium borate (up to 100 mM, pH 8.5) also
      caused protein ion suppression, but especially with the borate buffer significant
      MS intensity remained. MS analysis of myoglobin revealed the loss of the heme
      group when an acidic CE electrolyte was used. Using a background electrolyte
      containing 25 mM ammonium borate (pH 8.5), it is demonstrated that a CE
      separation of a protein test mixture can be monitored with ESI-MS without
      degrading the MS performance allowing molecular weight determinations of the
      separated compounds. In the presence of borate, detection limits were estimated
      to be 5-10 microM (ca. 100 fmol injected). The usefulness of the CE-MS system
      employing a borate buffer is indicated by the analysis of a stored sample of BSA
      revealing several degradation products. A sample of placental alkaline
      phosphatase (PLAP), a potential therapeutic agent, was also analyzed by CE-MS
      indicating the presence of a protein impurity. Probably due to insufficient
      ionization of the PLAP (a complex glycoprotein), no MS signals of the intact
      protein were observed.

PMID- 14730568
TI  - Analytical potential of enzyme-coated capillary reactors in capillary zone
      electrophoresis.
AB  - Enzymes immobilized on the inner surface of an electrophoretic capillary were
      used to increase sensitivity and resolution in capillary zone electrophoresis
      (CZE). Sensitivity is enhanced by inserting a piece of capillary containing the
      immobilized enzyme into the main capillary, located before the detector, in order
      to transform the analyte into a product with a higher absorptivity. This approach
      was used to determine ethanol. In order to improve resolution, capillary pieces
      containing immobilized enzymes were inserted at various strategic positions along
      the electrophoretic capillary. On reaching the enzyme, the analyte was converted
      into a product with a high electrophoretic mobility, the migration time for which
      was a function of the position of the enzyme reactor. This approach was applied
      to the separation and determination of acetaldehyde and pyruvate. Finally, the
      proposed method was validated with the determination of ethanol, acetaldehyde,
      and pyruvate in beer and wine samples.

PMID- 14730569
TI  - Detection of the major mutation M467T causing cystinuria by single-strand
      conformation polymorphism analysis using capillary electrophoresis.
AB  - We present a fast detection of M467T, the major mutation causing cystinuria, by
      capillary electrophoresis version of single-strand conformation polymorphism
      (SSCP). The DNA fragment (317 bp) carrying the point mutation was amplified by
      polymerase chain reaction (PCR) on the exon 8 of the SLC3A1 gene, which encodes
      for the transmembrane glycoprotein rBAT, a part of the active cystine and dibasic
      amino acids transporter. The complementary strands of the fragment were labeled
      by fluorescein and TAMRA, respectively. Thus, the electromigration of both
      strands was recorded independently as a laser-induced fluorescence (LIF) signal,
      what enabled an effective optimization of separation conditions. The injected
      sample was denatured by immersing the inlet of the separation capillary into a
      vial with 0.1 M solution of NaOH prior to analysis. Under optimum conditions, the
      SSCP analysis in poly(vinyl alcohol) (PVA)-coated silica-fused capillary of an
      effective length of 15 cm, filled with 4% linear polyacrylamide (LPA) solution,
      was accomplished in approximately 6 min. The experimentally observed mobility
      shifts of single-stranded DNA (ssDNA) fragments were compared to the appearance
      of their calculated two-dimensional conformations using Version 3.0 of MFOLD
      software. The number of nucleotides involved in the duplex regions of theoretical
      structures correlates well with their real migration order in the sieving medium.

PMID- 14730570
TI  - Effective sorbents for solid-phase extraction in the analysis of quinolones in
      animal tissues by capillary electrophoresis.
AB  - In this work, several commercial sorbents (Zorbax C18, Bond Elut C18, Isolute
      ENV+, Oasis HLB, Oasis MAX, SDB-RPS, and MPC-SD) were compared for the solid
      phase extraction of the series of quinolones regulated by the European Community
      in chicken tissues in order to establish a method for the determination of this
      series of quinolones by capillary electrophoresis and diode array detection.
      Sorbents were chosen in order to achieve maximum recoveries and optimal clean-up
      efficiency. Better results were obtained using SDB-RPS and Oasis MAX which would
      provide suitable limits of detection, below of the maximum residue limits (MRLs)
      regulated.

PMID- 14730571
TI  - Microemulsion electrokinetic chromatography with laser-induced fluorescence
      detection for sensitive determination of ephedrine and pseudoephedrine.
AB  - A selective and sensitive microemulsion electrokinetic chromatography with laser
      induced fluorescence detection method was developed for the quantification of
      ephedrine (E) and pseudoephedrine (PE) derivatized with 4-chloro-7-nitrobenzo-2
      oxa-1, 3-diazol. By a series of optimization, a running buffer composed of 20 mM
      borate + microemulsion (23.3 mM Sodium dodecyl sulfate/180.85 mM 1-butanol/16.4
      mM n-heptane) +8% acetonitrile was applied for the separation of the derivatives.
      A linear relationship for E and PE was obtained in the range of 0.058-11.58
      microg.mL(-1) (correlation coefficient: 0.9993 for E, 0.9995 for PE), and the
      detection limits for E and PE were 5.3 and 3.9 ng.mL(-1). The method was applied
      to the analysis of the two alkaloids in Chinese traditional herbal preparations
      with recoveries in the range of 96.9-105.4%.

PMID- 14730572
TI  - Microemulsion electrokinetic chromatography of drugs varying in charge and
      hydrophobicity: I. Impact of parameters on separation performance evaluated by
      multiple linear regression models.
AB  - The separation of anionic, cationic and neutral drugs in microemulsion
      electrokinetic chromatography (MEEKC) was studied with a statistical experimental
      design. The concentration of sodium dodecyl sulfate (SDS, surfactant), 1-butanol
      (co-surfactant) and borate buffer and the factors Brij 35 (surfactant), 2
      propanol (organic solvent) and cassette temperature were varied simultaneously,
      while the parameters pH (9.2), the concentration of octane (oil, 0.8% w/w), the
      voltage (10 kV) and the dimension of the fused-silica capillary, were kept
      constant. Eight different model substances were chosen with different
      hydrophobicities. Two of the analytes were positively charged, two were
      negatively charged, and the remaining four were neutral or close to neutral at
      the pH explored. The importance of each parameter on the separation window, the
      plate height and the retention factor for each of the analytes was studied by
      means of multiple linear regression (MLR) models. A new response was evaluated
      for anions, the quotient between the effective mobility in the microemulsion and
      the effective mobility in the corresponding buffer. Factors affecting selectivity
      changes were also explored, and it was found that SDS and 2-propanol had the
      largest effect on selectivity.

PMID- 14730573
TI  - Capillary electrophoresis of amphipathic alpha-helical peptide diastereomers.
AB  - We have made a rigorous assessment of the ability of capillary electrophoresis to
      resolve peptide diastereomers through its application to the separation of a
      series of synthetic 18-residue, amphipathic alpha-helical monomeric peptide
      analogues, where a single site in the centre of the hydrophobic face of the alpha
      helix is substituted by 19 L- or D-amino acids. Such L- and D-peptide pairs have
      the same mass-to-charge ratio, amino acid sequence and intrinsic hydrophobicity,
      varying only in the stereochemistry of one residue. CE approaches assessed in
      their ability to separate diastereomeric peptide pairs included capillary zone
      electrophoresis (uncoated capillary), micellar electrokinetic chromatography
      (uncoated capillary in the presence of 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate, CHAPS), open-tubular capillary electrochromatography (C(8)
      coated capillary in the presence of 25% 2,2,2-trifluoroethanol (TFE) or 25%
      ethanol). Overall, the OT-CEC methods were the most effective at separating the
      most peptide pairs, particularly for those containing hydrophilic side chains.
      However, the MEKC approach proved most effective for separation of peptide pairs
      containing hydrophobic or aromatic side chains.

PMID- 14730574
TI  - Analysis of cyanobacterial toxins (anatoxin-a, cylindrospermopsin, microcystin
      LR) by capillary electrophoresis.
AB  - Capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography
      (MEKC) were applied to the simultaneous separation of cyanobacterial toxins
      (anatoxin-a, microcystin-LR, cylindrospermopsin). The analytical performance data
      of both methods, optimized for the three toxins, were similar with a precision of
      migration times smaller than 0.8 RSD% and a detection limit in the range of 1-4
      microg/mL, using spectrophotometric detection at 230 nm. Both methods were
      applied to an analysis of cyanotoxins in water bloom samples and crude
      cyanobacterial extracts. The results obtained indicate that, for complex
      matrices, the sequential application of CZE and MEKC is necessary. It is
      recommended to use both CE techniques for the analysis of the same sample in
      order to confirm the results by an orthogonal approach.

PMID- 14730575
TI  - Vapor and liquid phase detection of cyanide on a microchip.
AB  - A capillary electrophoresis microchip is used to selectively and sensitively
      monitor cyanide levels in both vapor (HCN((g))) and aqueous (NaCN in drinking
      water) phases. Laser-induced fluorescence detection is applied using a violet
      diode laser to monitor the fluorescent isoindole derivative formed by the
      reaction of cyanide with 2,3-naphthalenedicarboxaldehyde (NDA) and taurine. Air
      sampling of hydrogen cyanide is achieved using a miniature impinger (2 mL),
      giving collection efficiencies as high as 79% for a sampling rate of 1.0 L/min
      and a 10 s sampling time (relative standard deviation RSD: 2.7% for n = 5).
      Following the addition of NDA and taurine to either the vapor phase impinger
      sample or an aqueous drinking water sample, the NDA/cyanide derivative can be
      detected in just over 40 s on the microchip, giving a detection limit of 0.56
      microg/L and a linear dynamic range from 0.56 microg/L-2.4 mg/L. The detection
      limit for hydrogen cyanide in air was determined to be 2.3 ppb (mole%). On-chip
      derivatization of cyanide by NDA was successful, although a 50% decrease in
      signal intensity was observed due to insufficient time for completion of the
      reaction on the microchip. A number of different interferents were examined, and
      only iron(II) and chlorine showed any interference due to their capability for
      masking the presence of cyanide by reacting with free cyanide in solution.

PMID- 14730576
TI  - Zeta potential determination by streaming current modelization and measurement in
      electrophoretic microfluidic systems.
AB  - Electrophoresis in capillary and microfluidic systems, used in analytical
      chemistry to separate charged species, are quite sensitive to surface phenomena
      in terms of separation performances. In order to improve theses performances, new
      surface functionalization techniques are required. There is a need for methods to
      provide fast and accurate quantification about surface charges at liquid/solid
      interfaces. We present a fast, simple, and low-cost technique for the measurement
      of the zeta-potential, via the modelization and the measurement of streaming
      currents. Due to the small channel cross section in microfluidic devices, the
      streaming current modelization is easier than the streaming potential
      measurement. The modelization combines microfluidic simulations based on the
      Navier-Stokes equation and charge repartition simulations based on the Poisson
      Boltzmann equation. This method has been validated with square and circular cross
      section shape fused-silica capillaries and can be easily transposed to any lab-on
      chip microsystems.

PMID- 14730577
TI  - Direct ampholyte-free liquid-phase isoelectric peptide focusing: application to
      the human serum proteome.
AB  - In this study, we utilized a multidimensional peptide separation strategy
      combined with tandem mass spectrometry (MS/MS) for the identification of proteins
      in human serum. After enzymatically digesting serum with trypsin, the peptides
      were fractionated using liquid-phase isoelectric focusing (IEF) in a novel
      ampholyte-free format. Twenty IEF fractions were collected and analyzed by
      reversed-phase microcapillary liquid chromatography (microLC)-MS/MS.
      Bioinformatic analysis of the raw MS/MS spectra resulted in the identification of
      844 unique peptides, corresponding to 437 proteins. This study demonstrates the
      efficacy of ampholyte-free peptide autofocusing, which alleviates peptide losses
      in ampholyte removal strategies. The results show that the separation strategy is
      effective for high-throughput characterization of proteins from complex proteomic
      mixtures.

PMID- 14730578
TI  - Alternative sample preparation prior to two-dimensional electrophoresis protein
      analysis on solid lipid nanoparticles.
AB  - The proteins adsorbing onto the surface of intravenously injected drug carriers
      are regarded as a key factor determining the organ distribution. Depending on the
      particle surface properties, certain proteins will be preferentially adsorbed,
      leading to the adherence of the particle to cells with the appropriate receptor.
      Therefore, the knowledge of the protein adsorption pattern and the correlation to
      in vivo behavior opens the perspective for the development of intravenous
      colloidal carriers for drug targeting. After incubation in plasma, the adsorbed
      proteins were analyzed using two-dimensional polyacrylamide gel electrophoresesis
      (2-D PAGE, 2-DE). The purpose of the present study was to develop an alternative
      separation method to separate solid lipid nanoparticles (SLN) carriers from
      plasma by gel filtration prior to 2-D PAGE. Via the specific absorption
      coefficients and a two-equation system, elution fractions were identified being
      practically plasma-free. This allows protein analysis on SLN which are typically
      in density too close to the density value of water to be separated by the
      standard centrifugation method. The SLN used for establishing the gel filtration
      were prepared in a way that they had a sufficiently low density to be
      additionally separated by centrifugation. The adsorption patterns obtained after
      separation with both methods were qualitatively and quantitatively identical,
      showing the suitability of the gel filtration.

PMID- 14730579
TI  - Profiling and comprehensive expression analysis of ABC transporter solute-binding
      proteins of Bacillus subtilis membrane based on a proteomic approach.
AB  - We analyzed ABC transporter solute-binding proteins (SBPs) of the Bacillus
      subtilis membrane using a proteomic approach. We prepared a washed cell membrane
      fraction that was insoluble in 134 mM nondetergent sulfobetaine and then
      extracted proteins using mixtures of detergents in a stepwise manner. The
      membrane proteins were resolved by three two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) or two one-dimensional (1-D) PAGE procedures,
      electroblotted, and digested in the presence of 5% or 80% acetonitrile.
      Thereafter, matrix-assisted laser desorption/ionization-time of flight-mass
      spectrometry (MALDI-TOF MS) identified 637 proteins corresponding to 15.9% of the
      total cellular proteins. We predicted that among these, 256 were membrane
      proteins, 101 were lipoproteins or secretory proteins and 280 were soluble
      proteins containing peripheral proteins that function in both the cytoplasm and
      the cell membrane such as SecA and FtsY. Among the 637 proteins, we identified 30
      SBPs among 38 importers predicted by a bioinformatic search of the genome. We
      confirmed expression of the genes for the 30 SBPs using DNA microarray analysis.
      We compared the 2-D gel separation profiles of submembrane fractions solubilized
      by 1% n-dodecyl-beta-D-maltoside from cells cultured on Luria Bertani (LB), S7,
      and S7 medium without glutamate as well as DNA microarray data on LB and S7. The
      results suggested that YcdH, YtmK and YurO are binding proteins for Mn(++),
      glutamate and glucose, respectively, and that YqiX and YxeM are binding proteins
      for amino acids (tryptophan in S7 medium).

PMID- 14730580
TI  - Comparative proteomics of human endothelial cell caveolae and rafts using two
      dimensional gel electrophoresis and mass spectrometry.
AB  - The human endothelial cell plasma membrane harbors two subdomains of similar
      lipid composition, caveolae and rafts, both crucially involved in various
      essential cellular processes like transcytosis, signal transduction and
      cholesterol homeostasis. Caveolin-enriched membranes, isolated by either cationic
      silica or buoyant density methods, were explored by comparing large series of two
      dimensional (2-D) maps and subsequent identification of over 100 protein spots by
      matrix-assisted laser desorption/ionization (MALDI) peptide mass fingerprinting.
      Improved representation and identification of membrane proteins and valuable
      information on various post-translational modifications was achieved by the
      presented optimized procedures for solubilization, destaining and database
      searching/computing. Whereas the cationic silica purification yielded
      predominantly known endoplasmic reticulum residents, the cold-detergent method
      yielded a large number of known caveolae residents, including caveolin-1. Thus, a
      large part of this subproteome was established, including known (trans-)membrane,
      signal transduction and glycosyl phosphatidylinositol (GPI)-anchored proteins.
      Several predicted proteins from the human genome were isolated for the first time
      from biological samples, including SGRP58, SLP-2, C8ORF2, and XRP-2. These
      findings and various optimized procedures can serve as a reference to study the
      differential composition of endothelial cell caveolae and rafts, known to be
      involved in pathologies like cancer and cardiovascular disease.

PMID- 14730581
TI  - Study of the development of thermoresistance in human pancreatic carcinoma cell
      lines using proteome analysis.
AB  - In order to find candidate proteins that are potentially associated with the
      thermoresistant phenotype in combination with drug resistance, we analyzed the
      differential protein expression in vitro in the human pancreatic cancer cell line
      EPP85-181-P and classical and atypical multidrug-resistant variants and their
      thermoresistant counterparts using proteomics. This study identifies sets of
      proteins that may lead to the development of thermoresistance. These results
      provide a fundamental basis to elucidate the molecular mechanism of
      thermoresistance and chemoresistance phenomena that may assist the therapy of
      inoperable cancers.

PMID- 14730584
TI  - Neural stem and progenitor cells in nestin-GFP transgenic mice.
AB  - Neural stem cells generate a wide spectrum of cell types in developing and adult
      nervous systems. These cells are marked by expression of the intermediate
      filament nestin. We used the regulatory elements of the nestin gene to generate
      transgenic mice in which neural stem cells of the embryonic and adult brain are
      marked by the expression of green fluorescent protein (GFP). We used these
      animals as a reporter line for studying neural stem and progenitor cells in the
      developing and adult nervous systems. In these nestin-GFP animals, we found that
      GFP-positive cells reflect the distribution of nestin-positive cells and
      accurately mark the neurogenic areas of the adult brain. Nestin-GFP cells can be
      isolated with high purity by using fluorescent-activated cell sorting and can
      generate multipotential neurospheres. In the adult brain, nestin-GFP cells are
      approximately 1,400-fold more efficient in generating neurospheres than are GFP
      negative cells and, despite their small number, give rise to 70 times more
      neurospheres than does the GFP-negative population. We characterized the
      expression of a panel of differentiation markers in GFP-positive cells in the
      nestin-GFP transgenics and found that these cells can be divided into two groups
      based on the strength of their GFP signal: GFP-bright cells express glial
      fibrillary acidic protein (GFAP) but not betaIII-tubulin, whereas GFP-dim cells
      express betaIII-tubulin but not GFAP. These two classes of cells represent
      distinct classes of neuronal precursors in the adult mammalian brain, and may
      reflect different stages of neuronal differentiation. We also found unusual
      features of nestin-GFP-positive cells in the subgranular cell layer of the
      dentate gyrus. Together, our results indicate that GFP-positive cells in our
      transgenic animals accurately represent neural stem and progenitor cells and
      suggest that these nestin-GFP-expressing cells encompass the majority of the
      neural stem cells in the adult brain.

PMID- 14730585
TI  - Neurogenesis and stereological morphometry of calretinin-immunoreactive GABAergic
      interneurons of the neostriatum.
AB  - We determined the neurogenesis characteristics of a distinct subclass of rat
      striatum gamma-aminobutyric acidergic (GABAergic) interneurons expressing the
      calcium-binding protein calretinin (CR). Timed-pregnant rats were given an
      intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU), a marker of cell
      proliferation, on designated days between embryonic day 12 (E12) and E21. CR
      immunoreactive (-IR) neurons and BrdU-positive nuclei were labeled in the adult
      neostriatum by double immunohistochemistry, and the proportion of double-labeled
      cells was quantified. CR-IR interneurons of the neostriatum show maximum birth
      rates (>10% double labeling) between E14 and E17, with a peak at E15. CR-IR
      interneurons occupying the lateral half of the neostriatum become postmitotic
      prior to medial neurons. In the precomissural neostriatum, the earliest-born
      neurons occupy the lateral quadrants and the latest-born neurons occupy the
      dorsomedial sector. No significant rostrocaudal neurogenesis gradient is
      observed. CR-IR neurons make up 0.5% of the striatal population and are localized
      in both the patch and the matrix compartments. CR-IR neurons of the patch
      compartment are born early (E13-15), with later-born neurons (E16-18) populating
      mainly the matrix compartment. CR-IR cells of the neostriatum are a distinct
      subclass of interneurons that are born at an intermediate time during striatal
      development and share common neurogenesis characteristics with other interneurons
      and projection neurons produced in the ventral telencephalon.

PMID- 14730586
TI  - Origin of cocaine- and amphetamine-regulated transcript (CART)-immunoreactive
      innervation of the hypothalamic paraventricular nucleus.
AB  - Axons containing cocaine- and amphetamine-regulated transcript (CART) densely
      innervate the hypothalamic paraventricular nucleus (PVN). Recent data from our
      laboratory demonstrated that CART-immunoreactive (IR) neurons of arcuate nucleus
      origin innervate the PVN, but comprise only a portion of the total CART-IR input
      to this region of the brain. To identify sources other than the arcuate nucleus,
      retrograde transport studies were performed with cholera toxin B subunit (CTB),
      focally delivered into the PVN of adult rats. Neurons double-labeled for CTB and
      CART were visualized by immunofluorescence. The most prominent groups of double
      labeled cells were identified in the retrochiasmatic area, arcuate nucleus,
      lateral hypothalamus, perifornical area, zona incerta, C1-3 regions, and the
      medial subnucleus of the nucleus tractus solitarius (NTS). In addition, scattered
      retrogradely labeled CART-IR neurons were found in the parabrachial nucleus. In
      the diencephalon, the majority of double-labeled neurons were localized
      ipsilateral to the injection site; however, in the medulla the CART/CTB
      containing neurons were found bilaterally. By triple-labeling immunofluorescence,
      CART/CTB neurons in the perifornical area, zona incerta complex, and more medial
      portions of the lateral hypothalamus were found to co-contain melanin
      concentrating hormone (MCH), whereas CART/CTB neurons of the C1-3 regions of the
      brainstem but not medial subnucleus of the NTS were observed to express
      phenylethanolamine N-methyltransferase (PNMT). We conclude that the CART
      innervation of the PVN derives from multiple neuronal sources of the hypothalamus
      and medulla. These observations raise the possibility that CART serves multiple
      functions in the PVN and is utilized to transmit diverse physiological signals
      that contribute to the complex regulation of homeostatic functions of the PVN.

PMID- 14730587
TI  - Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis.
AB  - Leber's congenital amaurosis (LCA) is the earliest and most severe form in the
      world of genetic retinal dystrophy causing blindness. An animal model of LCA was
      recently created in which the cone-rod homeobox (crx) gene was disrupted using
      homologous recombination. Crx-/- mice display abnormal development of
      photoreceptors followed by their degeneration. We analyzed the morphology of
      inner retinal cells in crx-/- mice in order to evaluate the effects of abnormal
      photoreceptor development and death upon other retinal neurons. The
      identification of a time window during which inner retinal cells are still viable
      could be very important in view of the possibilities that photoreceptor
      transplantation or gene therapy might be used to restore vision in LCA. We used a
      combination of immunocytochemical and confocal microscopy techniques to screen
      the crx-/- inner retina and verify its morphological integrity after
      photoreceptor degeneration. We found significant morphological alterations in
      second-order neurons in crx-/- animals. The appearance of mutant retinas after
      photoreceptor death is indistinguishable from that of the retinal degeneration
      (rd/rd) mouse, a different genetic model of a retinal disease characterized by
      photoreceptor degeneration. However, at early stages of photoreceptor
      degeneration the morphology of retinal cells in the crx-/- mutant is considerably
      well preserved. It is likely that different genetic mechanisms that cause
      abnormal photoreceptor development and/or degeneration lead to a common pathway
      that determines second-order neuron modifications. The severity of modifications
      is linked to the timing of onset of the degeneration and appears to increase with
      time.

PMID- 14730588
TI  - Morphologic analysis and classification of ganglion cells of the chick retina by
      intracellular injection of Lucifer Yellow and retrograde labeling with DiI.
AB  - Retinal ganglion cells (RGCs) of chicks were labeled by using the techniques of
      intracellular filling with Lucifer Yellow and retrograde axonal labeling with
      carbocyanine dye (DiI). Labeled RGCs were morphologically analyzed and classified
      into four major groups: Group I cells (57.1%) with a small somal area (77.5
      microm(2) on average) and narrow dendritic field (17,160 microm(2) on average),
      Group II cells (28%) with a middle-sized somal area (186 microm(2)) and middle
      sized dendritic field (48,800 microm(2)), Group III cells (9.9%) with a middle
      sized somal area (203 microm(2)) and wide dendritic field (114,000 microm(2)),
      and Group IV cells (5%) with a large somal area (399 microm(2)) and wide
      dendritic field (117,000 microm(2)). Of the four groups, Groups I and II were
      further subdivided into two types, simple and complex, on the basis of dendritic
      arborization: Groups Is, Ic, and Groups IIs, IIc. However, Group III and IV
      showed either a simple or complex type, Group IIIs and Group IVc, respectively.
      The density of branching points of dendrites was approximately 10 times higher in
      the complex types (18,350, 6,190, and 3,520 points/mm(2) in Group Ic, IIc, and
      IVc, respectively) than in the simple types (1,890, 640, and 480 points/mm(2) in
      Group Is, IIs, and IIIs). The branching density of Group I cells was extremely
      high in the central zone. The chick inner plexiform layer was divided into eight
      sublayers by dendritic strata of RGCs and 26 stratification patterns were
      discriminated. The central and peripheral retinal zones were characterized by
      branching density of dendrites and composition of RGC groups, respectively.

PMID- 14730589
TI  - Cellular correlates of progressive hearing loss in 129S6/SvEv mice.
AB  - Several strains of mice hear well initially but show progressive sensorineural
      hearing loss. Affected cochlear cell types include all those known to be affected
      in human age-related hearing loss (ARHL), or presbycusis. Thus these mice have
      been offered as models of human ARHL. At present, however, few mouse ARHL models
      are sufficiently well described to serve as the basis for specific hypotheses
      about human ARHL. We examined 1-month-old and 15-month-old 129S6/SvEv (129S6)
      mice and compared them with BALB/cJ and CBA/J mice. Age-related elevation of
      compound action potential thresholds was interpreted in the light of endocochlear
      potentials and changes in hair cells, afferent neurons, fibrocytes in spiral
      limbus and ligament, and supporting cells within the organ of Corti. Aging in
      129S6 mice was associated with high-frequency hearing loss. Four components of
      age-related cochlear degeneration emerged from quantitative analyses, including
      1) basal loss of outer hair cells; 2) basal loss of type IV fibrocytes in the
      spiral ligament; 3) apical loss of fibrocytes in spiral limbus, and 4) anomalies
      of supporting cells in the cochlear base. Although neuronal loss was not
      consistently found, two mice showed loss of afferent dendrites and cell bodies in
      the cochlear apex without inner hair cell loss. Despite multifaceted
      degeneration, hearing loss in 129S6 mice appears to be best explained by
      degenerative changes in outer hair cells and in the organ of Corti, conforming to
      human sensory ARHL. Age-related changes in the apical spiral limbus may promote
      pathology of the medial organ of Corti and eventual loss of afferent neurons,
      with possible implications for human neural ARHL.

PMID- 14730590
TI  - Medullary and spinal cord projections from cardiovascular responsive sites in the
      rostral ventromedial medulla.
AB  - The rostral ventromedial medulla (RVMM) is a sympathoexcitatory area. However,
      little is known about its efferent projections. In this study, biotinylated
      dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHA-L) were used to
      investigate the medullary and spinal cord projections from pressor sites in RVMM.
      Initially, RVMM was systematically explored in urethane-anesthetized rats using
      microinjection of L-glutamate for sites that elicited increases in arterial
      pressure. A pressor area was identified that included the rostral magnocellular
      reticular and rostral lateral paragigantocellular reticular nuclei. In the second
      series of experiments, BDA or PHA-L was iontophoretically injected into RVMM
      pressor sites. Anterograde labeling was observed throughout the brainstem and
      spinal cord, bilaterally, but with an ipsilateral predominance. Dense labeling
      was observed within the nucleus of the solitary tract (NTS); the greatest density
      of labeling was observed in the caudal dorsolateral, medial, and ventrolateral
      subnuclei. Additionally, light to moderately dense labeling was found within the
      nucleus substantia gelatinosus and commissural nucleus. In the nucleus
      ambiguus/ventrolateral medullary (Amb/VLM) region, the density of labeling was
      greatest in caudal regions. Within Amb, most of the labeling was localized to its
      external formation. Anterograde labeling was also found throughout the spinal
      cord. In the thoracolumbar segments, dense axonal labeling was observed within
      the dorsolateral funiculus. These labeled axons innervated the intermediolateral
      nucleus and the central autonomic area. Taken together, these data suggest that
      RVMM neurons elicit increases in sympathetic activity by likely providing a
      direct excitatory input to spinal sympathetic preganglionic neurons, and by a
      direct inhibitory input to medullary cardioinhibitory and depressor areas.

PMID- 14730591
TI  - Development of vimentin and glial fibrillary acidic protein immunoreactivities in
      the brain of gray mullet (Chelon labrosus), an advanced teleost.
AB  - Previous studies in teleosts have revealed the presence of the intermediate
      filaments vimentin (Vim) and glial fibrillary acidic protein (GFAP) in glial
      cells of the spinal cord and/or some brain regions, but there is no comprehensive
      study of their distribution and developmental changes in fishes. Here, the
      distribution of Vim and GFAP immunoreactivities was studied in the brain of
      larvae, juveniles, and adults of an advanced teleost, the gray mullet (Chelon
      labrosus). A different sequence of appearance was observed for expression of
      these proteins: Vim levels decreased with age, whereas GFAP increased. In
      general, both immunoreactivities were expressed early in perikarya and endfeet of
      ependymocytes (tanycytes), whereas expression in radial processes appeared later.
      In large larvae, the similar expression patterns of Vim and GFAP suggest that
      some of these glial cells contain both proteins. Subependymal radial glia cells
      were observed mainly in the optic tectum, exhibiting Vim and GFAP
      immunoreactivity. The only immunoreactive cells with astrocyte-like morphology
      were observed in the optic chiasm of the adult, and they were positive for both
      GFAP and Vim. The perivascular processes of glial cells showed a different
      distribution of Vim and GFAP during development and had a caudorostral sequence
      of appearance of immunoreactivities similar to that observed for ependymal and
      radial glia cells. Several circumventricular organs (the organon vasculosum
      hypothalami, saccus vasculosus, and area postrema) exhibited highly specialized
      Vim- and/or GFAP-expressing glial cells. The glial cells of the midline septa of
      several brain regions were also Vim and/or GFAP immunoreactive. In the adult
      brain, tanycytes retain Vim expression in several brain regions. As in other
      vertebrates, the regions with Vim-immunoreactive ventricular and midline glia may
      represent areas with the capability of plasticity and regeneration in adult
      brain.

PMID- 14730592
TI  - Efferent connections of septal nuclei of the domestic chick (Gallus domesticus):
      an anterograde pathway tracing study with a bearing on functional circuits.
AB  - Small iontophoretic injections of the anterograde tracer Phaseolus vulgaris
      leucoagglutinin were placed in different subregions of the septum of domestic
      chicks. The main targets of septal projections comprised the ipsi- and
      contralateral septal nuclei, including the nucleus of the diagonal band, basal
      ganglia, including the ventral paleostriatum, lobus parolfactorius, nucleus
      accumbens, and olfactory tubercle, archistriatum, piriform cortex, and anterior
      neostriatum. Further diencephalic and mesencephalic septal projections were
      observed in the ipsilateral preoptic region, hypothalamus (the main regions of
      afferentation comprising the lateral hypothalamic nuclei, ventromedial,
      paraventricular and periventricular nuclei, and the mammillary region), dorsal
      thalamus, medial habenular and subhabenular nuclei, midbrain central gray, and
      ventral tegmental area. Contralateral projections were also encountered in the
      septal nuclei, ventral paleostriatum, periventricular and anteromedial
      hypothalamic nuclei, suprachiasmatic nucleus, and the lateral hypothalamic area.
      Avian septal efferents are largely similar to those of mammals, the main
      differences being a relatively modest hippocampal projection arising mainly from
      the nucleus of the diagonal band (as confirmed by a specific experiment with the
      retrograde pathway tracer True blue), the lack of interpeduncular projection, and
      a greater contingent of amygdalar efferents arising from the lateral septum
      rather than the nucleus of the diagonal band. This pattern of connectivity is
      likely to reflect an important role of the avian septal nuclei in the
      coordination of limbic circuits and the integration of a wide variety of
      information sources modulating the appropriate behavioral responses: attention
      and arousal level, memory formation, hormonally mediated behaviors, and their
      affective components (such as ingestive, reproductive, and parental behaviors),
      social interaction, locomotor modulation, and circadian rhythm.

PMID- 14730593
TI  - The synovium in rheumatoid arthritis: evidence for (at least) two pathologies.

PMID- 14730594
TI  - Magnetic resonance imaging as a noninvasive means for quantitating the dimensions
      of articular cartilage in the human knee.

PMID- 14730595
TI  - Physiologic responses to hypoxia and implications for hypoxia-inducible factors
      in the pathogenesis of rheumatoid arthritis.

PMID- 14730596
TI  - Assessment of patients with psoriatic arthritis: a review of currently available
      measures.

PMID- 14730597
TI  - Progression of radiologic damage in patients with rheumatoid arthritis in
      clinical remission.
AB  - OBJECTIVE: To assess whether radiologic progression occurs during clinical
      remission in patients with rheumatoid arthritis (RA). METHODS: One hundred eighty
      seven patients with RA in clinical remission were followed up clinically and
      radiologically for 2 years. Clinical remission was defined according to a
      modification of the American College of Rheumatology criteria (i.e., the
      criterion of fatigue was omitted, and patients had to fulfill 4 of the 5
      remaining criteria). Radiologic joint damage was assessed by the Sharp/van der
      Heijde method. RESULTS: After 2 years of followup, remission persisted in 52% of
      patients. The median radiologic score for the total group of patients increased
      from 21 (interquartile range [IQR] 5, 65) at the time of entry to 25 (IQR 7, 72)
      after 2 years (P < 0.001). The median score for radiologic progression between
      baseline and 2 years was 0.5 (IQR 0, 2.5). Among patients with an exacerbation of
      RA (n = 86), the median score for progression over 2 years was 1.0 (IQR 0, 4.5)
      (P < 0.001), and in patients with a persistent remission (n = 93) it was 0 (IQR 
      0.5, 2.0) (P < 0.001). Clinically relevant progression of damage was more
      frequent in patients with exacerbation (23%) than in those with persistent
      remission (7%) (P = 0.001). However, in 15% of patients with persistent
      remission, an erosion developed in a previously unaffected joint. In the logistic
      regression analysis, the area under the curve of the Disease Activity Score, a
      continuous measure, was related to the chance of radiologic progression,
      regardless of the absolute disease activity level. Results were similar when
      other definitions of remission were used. CONCLUSION: Although rare, clinically
      relevant progression of joint damage does occur in patients with RA in prolonged
      remission. This suggests the need for markers that predict progression during
      periods of low disease activity and for drugs that prevent damage that is
      independent of disease activity.

PMID- 14730598
TI  - Prognostic markers of radiographic progression in early rheumatoid arthritis.
AB  - OBJECTIVE: To identify prognostic markers that are predictive of progressive
      erosive disease in patients with early rheumatoid arthritis (RA). METHODS: The
      study involved an inception cohort of 111 consecutive patients with RA and a
      disease duration of <1 year. Patients were treated according to an algorithm
      designed to avoid overtreatment of mild disease and to accelerate treatment in
      patients who had continuous disease activity. Patients were evaluated for the
      presence of clinical and laboratory disease activity markers. We determined the
      frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene
      polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single
      nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization
      to an immobilized probe array. Data were analyzed using proportional odds models
      to identify prognostic markers predictive of erosive progression over 2 years on
      serial hand/wrist radiographs. RESULTS: After 2 years, disease activity in 52% of
      the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal
      agents. Forty-eight percent of the patients did not develop erosions. Older age,
      presence of erosions at baseline, presence of rheumatoid factor, rheumatoid
      factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04,
      were univariate predictors of radiographic progression. Promising novel markers
      were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator,
      and a polymorphism in the uteroglobin gene. CONCLUSION: Clinical disease activity
      in patients with early RA can frequently be controlled with nonaggressive
      treatment, but this is not always sufficient to prevent new erosions. Rheumatoid
      factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are
      predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene
      may identify patients who have a low risk of erosive disease.

PMID- 14730599
TI  - Impact of initial aggressive drug treatment with a combination of disease
      modifying antirheumatic drugs on the development of work disability in early
      rheumatoid arthritis: a five-year randomized followup trial.
AB  - OBJECTIVE: To compare the efficacy of therapy with a combination of disease
      modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the
      prevention of work disability in patients with early rheumatoid arthritis (RA).
      METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195
      patients with recent-onset RA were randomly assigned to receive either
      combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine)
      plus prednisolone or single therapy with a DMARD with or without prednisolone.
      After 2 years, the drug treatment strategy was no longer restricted. At baseline,
      162 patients (80 in the combination-treatment group and 82 in the single
      treatment group) were still working or at least available for work. After 5 years
      of followup, data on all sick leave and retirement were obtained from social
      insurance registers or case records. The main outcome for each patient was the
      cumulative duration of all sick leaves and RA-related disability pensions,
      divided by the observation period during which the patient was not retired
      because of another disease or because of age. RESULTS: The cumulative duration of
      work disability per patient-observation year was significantly lower in those
      randomized to combination therapy than in those randomized to single therapy:
      median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P
      = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference
      in sick leaves (i.e., work disability periods </=300 days): median 11.7 days (IQR
      0-44) per patient-observation year in those treated with combination therapy and
      30.0 days (IQR 6-68) in those treated with single therapy (P = 0.002). No
      statistically significant difference was seen in RA-related disability pensions.
      CONCLUSION: Aggressive initial treatment of RA with a combination of DMARDs
      improves 5-year outcome in terms of lost productivity in patients with RA of
      recent onset.

PMID- 14730600
TI  - Analysis of single-nucleotide polymorphisms in Japanese rheumatoid arthritis
      patients shows additional susceptibility markers besides the classic shared
      epitope susceptibility sequences.
AB  - OBJECTIVE: To examine the entire HLA region for loci (other than the DRB1 locus)
      associated with rheumatoid arthritis (RA) susceptibility, by typing HLA-DRB1
      alleles and multiple single-nucleotide polymorphisms (SNPs) in the Japanese
      population. METHODS: The HLA-DRB1 alleles and 88 SNPs distributed over the HLA
      gene complex were genotyped, for 828 patients with RA and 1,032 control subjects.
      The data were evaluated for linkage disequilibrium, and case-control associations
      were analyzed in 2 ways, in the presence or absence of the disease-susceptibility
      DRB1 allele, to detect loci independent of the DRB1 allele. RESULTS: HLA-DRB1
      alleles *0405, *0401, *0901, *0101, *1401, *1602, *0403, and *1405 were
      significantly associated with RA in the Japanese population. The smallest P value
      (P = 1.4 x 10(-27)) was observed in association with an intronic SNP of the
      NOTCH4 gene, which was due to strong linkage disequilibrium with the HLA-DRB1
      allele. A strong association that was independent of HLA-DRB1 shared epitope
      alleles was observed in 2 SNPs: one in the intron of the MICA gene, the other in
      the intron of the HLA-DQB2 gene. Their association with RA, independent of HLA
      DRB1 shared epitope alleles, was suggestive (P = 0.0024 [corrected P (P(corr)) =
      0.068, and P = 0.00037 [P(corr) = 0.012], respectively). CONCLUSION: These
      findings suggest that 1 or more other loci besides the HLA-DRB1 or other DRB1
      (non-shared epitope, non-*0901) alleles are involved in RA
      susceptibility/protection.

PMID- 14730601
TI  - Vitamin D intake is inversely associated with rheumatoid arthritis: results from
      the Iowa Women's Health Study.
AB  - OBJECTIVE: Vitamin D is a potent regulator of calcium homeostasis and may have
      immunomodulatory effects. The influence of vitamin D on human autoimmune disease
      has not been well defined. The purpose of this study was to evaluate the
      association of dietary and supplemental vitamin D intake with rheumatoid
      arthritis (RA) incidence. METHODS: We analyzed data from a prospective cohort
      study of 29,368 women of ages 55-69 years without a history of RA at study
      baseline in 1986. Diet was ascertained using a self-administered, 127-item
      validated food frequency questionnaire that included supplemental vitamin D use.
      Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox
      proportional hazards regression, adjusting for potential confounders. RESULTS:
      Through 11 years of followup, 152 cases of RA were validated against medical
      records. Greater intake (highest versus lowest tertile) of vitamin D was
      inversely associated with risk of RA (RR 0.67, 95% CI 0.44-1.00, P for trend =
      0.05). Inverse associations were apparent for both dietary (RR 0.72, 95% CI 0.46
      1.14, P for trend = 0.16) and supplemental (RR 0.66, 95% CI 0.43-1.00, P for
      trend = 0.03) vitamin D. No individual food item high in vitamin D content and/or
      calcium was strongly associated with RA risk, but a composite measure of milk
      products was suggestive of an inverse association with risk of RA (RR 0.66, 95%
      CI 0.42-1.01, P for trend = 0.06). CONCLUSION: Greater intake of vitamin D may be
      associated with a lower risk of RA in older women, although this finding is
      hypothesis generating.

PMID- 14730602
TI  - Retinoblastoma suppression of matrix metalloproteinase 1, but not interleukin-6,
      through a p38-dependent pathway in rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by increased synovial
      lining cellularity, inflammation, and destruction of cartilage and bone. During
      the pathogenesis of RA, synovial fibroblasts reenter the cell cycle and multiply
      in number. RA synovial fibroblasts express high levels of the MAP kinase p38,
      which may contribute to the production of interleukin-6 (IL-6) and matrix
      metalloproteinases (MMPs). IL-6 and MMP-1 promote inflammation and joint
      destruction, respectively. Taken together, these findings indicate that in RA the
      enhanced cell cycle activity and production of IL-6 and MMP-1 may be linked.
      Therefore, we sought to determine if the tumor suppressor gene product
      retinoblastoma (Rb), a negative regulator of cell cycle activity, inhibits IL-6,
      MMP-1, and p38 in RA synovial fibroblasts. METHODS: RA and non-RA synovial
      fibroblasts were examined by enzyme-linked immunosorbent assay (ELISA) for the
      relative expression of inactive hyperphosphorylated Rb (inactive Rb/total Rb).
      Ectopic Rb expression was mediated by infection with a replication-defective
      adenovirus that expresses Rb (Ad-Rb). A control replication-defective adenovirus
      that expresses beta-galactosidase (Ad-beta-gal) was used. Cell cycle activity was
      determined by flow cytometry. IL-6 and MMP-1 expression was examined by real-time
      polymerase chain reaction and ELISA. Expression and activation of p38 were
      determined by kinase assays and ELISA. The activity of p38 was enhanced by
      infecting RA synovial fibroblasts with a replication-defective adenovirus that
      expresses a constitutively active form of MAPK kinase 3 (Ad-CA-MKK3), an upstream
      activator of p38. RESULTS: Quiescent RA, compared with non-RA synovial
      fibroblasts, displayed a 200% (P < 0.02) increase in the inactive Rb isoform.
      Proliferating RA synovial fibroblasts exhibited a 60% (P < 0.12) increase in the
      inactive Rb isoform compared with non-RA synovial fibroblasts. Increased levels
      of the active Rb isoform inhibited cell cycle progression and suppressed IL-6 and
      MMP-1 secretion in RA synovial fibroblasts, although the steady-state levels of
      IL-6 and MMP-1 messenger RNA remained unchanged. However, Rb overexpression had
      no effect on spontaneous or IL-1beta-induced production of IL-6 or MMP-1 in non
      RA synovial fibroblasts. Ectopic Rb expression reduced the activity of p38. Ad-CA
      MKK3 infection in RA synovial fibroblasts increased p38 phosphorylation, and MMP
      1 but not IL-6 secretion. In contrast, Rb overexpression inhibited Ad-CA-MKK3
      mediated phosphorylation of p38 and subsequent increase in MMP-1. CONCLUSION: Rb
      mediated suppression of IL-6 and MMP-1 occurs at a posttranscriptional level.
      However, Ad-Rb reduction of MMP-1 but not IL-6 requires inhibition of the p38
      pathway. These results suggest that Rb negatively regulates p38 activation,
      leading to decreased MMP-1 secretion in RA synovial fibroblasts.

PMID- 14730603
TI  - Continuous enhanced expression of Hsc70 but not Hsp70 in rheumatoid arthritis
      synovial tissue.
AB  - OBJECTIVE: To investigate the expression of constitutive and inducible members of
      the Hsp70 protein family in synovial tissue of patients with rheumatoid arthritis
      (RA) or osteoarthritis (OA). METHODS: Frozen sections of synovial tissue and
      isolated synovial adherent cells obtained from 17 RA patients, 5 OA patients, and
      1 patient with carpal tunnel syndrome (CTS) were analyzed with specific
      monoclonal antibodies, by immunohistochemistry, immunocytochemistry, and
      immunoblotting. RESULTS: Expression of the constitutive chaperone Hsc70 was
      increased in synovial tissue from 9 of 9 patients with RA, but was faint or
      undetectable in 3 of 3 samples from patients with OA. In RA samples, cells mainly
      of the synovial lining stained intensely for Hsc70 as well as for HLA-DR, CD14,
      and CD68. Also, in vitro-cultured synovial adherent cells from 8 of 9 RA patients
      overexpressed Hsc70 (specimens from 1 RA patient were used in both the
      immunochemistry and the in vitro culture studies). On immunoblots of protein
      extracts, the synovial and HeLa cell molecules appeared identical in size. The
      inducible chaperone Hsp70 was not detected in samples from any of the same 17 RA
      patients, except for rare, isolated cells in 3. Samples from 4 of 5 OA patients
      also were negative for the inducible chaperone Hsp70, and the fifth was very
      weakly positive. In addition, tissue from 1 patient with CTS was analyzed 10
      months before diagnosis of RA. Synovial tissue from this patient showed extreme
      overexpression of both Hsc70 and Hsp70. CONCLUSION: In RA, synovial lining cells
      continuously overexpress Hsc70 but not Hsp70. Hsc70 may be up-regulated due to
      the high activity of these cells in several respects, including antigen
      processing and presentation.

PMID- 14730604
TI  - Longitudinal study of changes in tibial and femoral cartilage in knee
      osteoarthritis.
AB  - OBJECTIVE: Despite the increasing interest in knee cartilage volume as an outcome
      measure in studies of osteoarthritis (OA), it is unclear what components of knee
      cartilage will be most useful as markers of structural change in the tibiofemoral
      joint. This study was undertaken to longitudinally compare changes in femoral and
      tibial cartilage volume in patients with OA. METHODS: One hundred seventeen
      patients with knee OA (58.1% women; mean +/- SD age 63.7 +/- 10.2 years) were
      examined. Femoral and tibial cartilage volumes (medial and lateral tibiofemoral
      joints) were determined from T1-weighted fat-saturated magnetic resonance images
      of the knee from coronal views. RESULTS: The study population was followed up for
      a mean +/- SD of 1.9 +/- 0.2 years. In the medial tibiofemoral joint, the mean +/
      SD loss of cartilage was 0.15 +/- 0.30 ml/year for femoral cartilage and 0.10 +/
      0.25 ml/year for tibial cartilage. In the lateral tibiofemoral joint, the
      average loss was 0.15 +/- 0.22 and 0.12 +/- 0.16 ml/year for femoral and tibial
      cartilage, respectively. There was a significant correlation between the degree
      of loss of tibial cartilage and the degree of loss of femoral cartilage, in both
      tibiofemoral joints (r = 0.81, P < 0.001 at the medial tibiofemoral joint; r =
      0.71, P < 0.001 at the lateral tibiofemoral joint). CONCLUSION: Longitudinal
      changes in tibial cartilage and those in femoral cartilage are strongly related
      to one another. This suggests that in tibiofemoral disease, measuring tibial
      cartilage alone may be adequate, given the facts that measurements of the total
      femoral cartilage are less reproducible and there are difficulties inherent in
      identifying the most appropriate component of femoral cartilage to measure.

PMID- 14730605
TI  - Finer linkage mapping of primary osteoarthritis susceptibility loci on
      chromosomes 4 and 16 in families with affected women.
AB  - OBJECTIVE: To more finely linkage-map primary osteoarthritis (OA) susceptibility
      loci on chromosomes 4 and 16. METHODS: Two hundred eighteen families, each with 2
      or more women concordant for primary OA (ascertained by total hip replacement
      [THR] or total knee replacement), were genotyped using highly polymorphic
      microsatellite markers from chromosomes 4 and 16, at an average density of 1
      marker every 4 cM. Two-point and multipoint linkage analyses were performed for
      all 218 families and for the 146 families from the 218 that included women
      concordant for THR (female-THR families). RESULTS: A single region of linkage was
      identified on chromosome 4q, with a maximum multipoint logarithm of odds (LOD)
      score (MLS) of 3.1 in the 146 female-THR families. This locus was centered 79 cM
      from the 4p telomere and had a 1-LOD support interval of 4 cM. Two regions of
      linkage were identified on chromosome 16, the first on 16p with an MLS of 1.7 in
      the female-THR families and the second on 16q with an MLS of 1.9 in all 218
      families. The first locus was centered 46 cM and the second 89 cM from the p
      telomere. The 1-LOD support intervals were 12 cM and 10 cM, respectively.
      CONCLUSION: Finer linkage mapping using a high density of microsatellite markers
      has narrowed female OA susceptibility loci on chromosomes 4 and 16. The regions
      have been narrowed sufficiently for association analysis.

PMID- 14730606
TI  - Crucial role of synovial lining macrophages in the promotion of transforming
      growth factor beta-mediated osteophyte formation.
AB  - OBJECTIVE: To investigate in vivo and in vitro whether macrophages have an
      intermediate role in transforming growth factor beta (TGFbeta)-induced osteophyte
      formation. METHODS: In vivo, synovial lining macrophages were selectively
      depleted by injection of clodronate-laden liposomes 7 days prior to injection of
      20 ng or 200 ng of TGFbeta into murine knee joints 3 times, on alternate days.
      Total knee joint sections were obtained on day 7 after the last injection and
      stained with Safranin O. Production of bone morphogenetic protein 2 (BMP-2) and
      BMP-4 was determined by immunolocalization. The interaction between murine
      macrophages and mesenchymal cells (precursors with chondrogenic potential) was
      studied in vitro using a Transwell system in which RAW macrophages were
      cocultured with C3H10T1/2 mesenchymal cells. Spheroid neocartilage formation was
      quantified microscopically after staining with May-Grunwald-Giemsa. RESULTS:
      Triple injections of 20 ng or 200 ng of TGFbeta into normal murine knee joints
      induced significant osteophyte formation at the lateral and medial sites of the
      patella and femur on day 7 after the last injection. Strikingly, removal of
      synovial lining macrophages prior to TGFbeta injection resulted in a drastic
      reduction of osteophyte formation (by 70% and 64% after injection of 20 ng and
      200 ng of TGFbeta, respectively). Synovial lining cells produced BMP-2 and BMP-4
      after TGFbeta stimulation, whereas BMP-2 and BMP-4 were absent in the synovial
      tissue after macrophage depletion. In vitro, clustering and spheroid formation of
      C3H10T1/2 was induced by TGFbeta concentrations of >1 ng/ml. However, in the
      Transwell system, in the presence of murine macrophages, 0.5 ng/ml of TGFbeta was
      very effective in generating large spheroids, suggestive of macrophage-derived
      (co)factors. In coculture supernatants, TGFbeta concentrations were not elevated
      in the presence of macrophages, indicating generation of other growth factors
      involved in spheroid formation. CONCLUSION: These findings indicate that
      macrophages are crucial intermediate factors in osteophyte formation induced by
      TGFbeta, probably by inducing other chondrogenic signals.

PMID- 14730607
TI  - A role for chemokines in the induction of chondrocyte phenotype modulation.
AB  - OBJECTIVE: To extend the study of the chemokine receptor repertoire on human
      chondrocytes to receptors with reported housekeeping functions (CXCR3, CXCR4,
      CXCR5, and CCR6) and to evaluate whether ligands of these receptors play a role
      in chondrocyte phenotype modulation and proliferation. METHODS: Chemokine
      receptor expression was determined by flow cytometry. Subcultures of chondrocytes
      were collected and fixed at confluence or during the exponential phase of growth
      and analyzed for chemokine receptor modulation. The effects of chemokines on
      isolated cells as well as chondrocytes cultured within an intact extracellular
      matrix were investigated. Isolated human chondrocytes were stimulated with 100 nM
      chemokines (monokine induced by interferon-gamma, stromal cell-derived factor
      1alpha [SDF-1alpha], B cell-attracting chemokine 1 [BCA-1], or macrophage
      inflammatory protein 3alpha), and conditioned media were assessed for matrix
      degrading enzyme contents (matrix metalloproteinases [MMPs] 1, 3, and 13, and N
      acetyl-beta-D-glucosaminidase [NAG]). Cell proliferation and phenotype modulation
      were evaluated by bromodeoxyuridine incorporation and cathepsin B production.
      Induction of cell proliferation was assessed in cartilage explants by
      immunodetection of the proliferation-associated antigen S100A4. RESULTS: CXCR3,
      CXCR4, CXCR5, and CCR6 were detected on human chondrocytes. CXCR3 and CXCR4
      expression was increased in exponentially growing chondrocyte subcultures.
      Ligands of all receptors enhanced the release of MMPs 1, 3, and 13. Release of
      NAG and cathepsin B was significantly higher in chemokine-stimulated cultures
      than in unstimulated cultures. SDF-1alpha and BCA-1 also induced DNA synthesis
      and chondrocyte proliferation, as was shown by the up-regulation of S100A4 in
      cartilage explants as well. CONCLUSION: Our findings extend the repertoire of
      functional responses elicited by the activity of chemokines on chondrocytes and
      open new avenues in our understanding of the control of chondrocyte
      differentiation status by chemokines and their receptors.

PMID- 14730608
TI  - Influence of tissue maturation and antioxidants on the apoptotic response of
      articular cartilage after injurious compression.
AB  - OBJECTIVE: To study the influence of tissue maturation and antioxidants on
      apoptosis in bovine articular cartilage induced by injurious compression.
      METHODS: Bovine articular cartilage disks were obtained from the femoropatellar
      groove of animals ages 0.5-23 months and placed in culture. Cartilage disks were
      preincubated overnight with the cell-permeable superoxide dismutase (SOD) mimetic
      Mn(III) porphyrin (0-12.5 microM) or alpha-tocopherol (0-50 microM) and then
      injured by a single unconfined compression to a final strain of 50% at a velocity
      of 1 mm/second. After 4 days of additional incubation, the disks were fixed and
      embedded for light and electron microscopy. Apoptotic cells were quantified
      morphologically by the appearance of nuclear blebbing on light microscopy.
      Biosynthetic activity was demonstrated by incorporation of radiolabeled proline.
      The antioxidative action of the SOD mimetic was confirmed by histologic
      examination of cartilage after incubation with nitroblue tetrazolium. RESULTS:
      Injurious compression induced significantly more apoptosis in cartilage disks
      from newborn calves (22% of cells) than in cartilage from more mature cows (2
      6%). In cartilage from 22-month-old animals, the SOD mimetic reduced the
      percentage of apoptotic cells induced by injury in a dose-dependent manner
      (complete inhibition with 2.5 microM), while alpha-tocopherol had no effect.
      Neither antioxidant altered protein biosynthesis or cellular ultrastructure.
      CONCLUSION: Our data suggest that the apoptotic response of articular cartilage
      to mechanical injury is affected by maturation and is mediated in part by
      reactive oxygen species. The antioxidative status of the tissue might be
      important for the prevention of mechanically induced cell death in articular
      cartilage.

PMID- 14730609
TI  - Expression profiling of metalloproteinases and their inhibitors in cartilage.
AB  - OBJECTIVE: To profile the expression of all known members of the matrix
      metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases
      (TIMP) gene families in normal cartilage and cartilage from patients with
      osteoarthritis (OA). METHODS: Human cartilage was obtained from femoral heads at
      joint replacement for OA or following fracture to the femoral neck. Total RNA was
      purified, and gene expression was assayed using quantitative real-time polymerase
      chain reaction. RESULTS: Several members of the above gene families were
      regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28,
      and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P <
      0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased
      expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1,
      and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P <
      0.05). Correlation analysis revealed that groups of genes across the gene
      families were coexpressed in cartilage. CONCLUSION: This is the first
      comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in
      cartilage. Elucidation of patterns of expression provides a foundation with which
      to understand mechanisms of gene regulation in OA and potentially to refine the
      specificity of antiproteolytic therapies.

PMID- 14730610
TI  - Failure of in vitro-differentiated mesenchymal stem cells from the synovial
      membrane to form ectopic stable cartilage in vivo.
AB  - OBJECTIVE: We previously reported the identification in a nude mouse assay of
      molecular markers predictive of the capacity of articular cartilage-derived cells
      (ACDCs) to form ectopic stable cartilage that is resistant to vascular invasion
      and endochondral ossification. In the present study, we investigated whether in
      vitro-differentiated mesenchymal stem cells (MSCs) from the synovial membrane
      (SM) express the stable-chondrocyte markers and form ectopic stable cartilage in
      vivo. METHODS: Chondrogenesis was induced in micromass culture with the addition
      of transforming growth factor beta1 (TGFbeta1). After acquisition of the
      cartilage phenotype, micromasses were implanted subcutaneously into nude mice.
      Alternatively, cells were released enzymatically and either replated in monolayer
      or injected intramuscularly into nude mice. Marker analysis was performed by
      quantitative reverse transcription-polymerase chain reaction. Cell death was
      detected with TUNEL assay. RESULTS: Cartilage-like micromasses and released cells
      expressed the stable-chondrocyte markers at levels comparable with those
      expressed by stable ACDCs. The released cells lost chondrocyte marker expression
      by 24 hours in monolayer and failed to form cartilage when injected
      intramuscularly into nude mice. Instead, myogenic differentiation was detected.
      When intact TGFbeta1-treated micromasses were implanted subcutaneously, they
      partially lost their cartilage phenotype and underwent cell death and
      neoangiogenesis within 1 week. At later time points (15-40 days), we retrieved
      neither cartilage nor bone, and human cells were not detectable. CONCLUSION: The
      chondrocyte-like phenotype of human SM MSCs, induced in vitro under specific
      conditions, appears to be unstable and is not sufficient to obtain ectopic
      formation of stable cartilage in vivo. Studies in animal models of joint surface
      defect repair are necessary to evaluate the stability of the SM MSC chondrocyte
      like phenotype within the joint environment.

PMID- 14730611
TI  - Comparison of risk factors for vascular disease in the carotid artery and aorta
      in women with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine and compare risk factors for various stages of subclinical
      vascular disease in different vascular beds (carotid and aorta) in women with
      systemic lupus erythematosus (SLE) who have not yet developed clinical
      cardiovascular disease. METHODS: This cross-sectional study was conducted in 214
      women without clinical cardiovascular disease who were enrolled in the Pittsburgh
      Lupus Registry. B-mode ultrasound was used to measure carotid plaque and intima
      media wall thickness (IMT). Doppler probes were used to collect pulse-wave
      velocity waveforms from the right carotid and femoral arteries as a measure of
      aortic stiffness. All risk factor data were collected on the day of the
      ultrasound examinations. RESULTS: The mean +/- SD age of the women was 45.2 +/-
      10.5 years and the median SLE disease duration was approximately 9 years. Sixty
      eight (32%) of the women had at least 1 focal plaque. The mean +/- SD IMT was
      0.71 +/- 0.1 mm, and the mean +/- SD pulse-wave velocity was 5.96 +/- 1.6
      meters/second. Using logistic regression, we found that determinants of plaque
      included older age, higher systolic blood pressure, lower levels of high-density
      lipoprotein 3, and antidepressant use. Determinants of plaque severity were older
      age, higher systolic blood pressure, lower levels of albumin, and smoking.
      Independent determinants of the highest quartile of IMT were older age, higher
      pulse pressure, lower levels of albumin, elevated C-reactive protein levels, high
      cholesterol, and higher levels of glucose. Higher aortic stiffness was associated
      with older age, higher systolic blood pressure, higher C3 levels, lower white
      blood cell count, higher insulin levels, and renal disease. CONCLUSION: In women
      with SLE, the risk factors associated with carotid plaque and IMT are those
      typically associated with cardiovascular disease in the general population,
      whereas the risk factors associated with vascular stiffness include SLE-specific
      variables related to immune dysregulation and complement metabolism. The high
      prevalence of cardiovascular disease among lupus patients may result from both
      early adverse effects on vascular stiffening as well as later promotion of wall
      thickening and plaque through inflammatory-mediated processes. These observations
      provide clues for future mechanistic studies.

PMID- 14730612
TI  - High insulin levels and increased low-density lipoprotein oxidizability in
      pediatric patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine low-density lipoprotein (LDL) size, LDL susceptibility to
      oxidation, and plasma insulin levels in children with systemic lupus
      erythematosus (SLE). METHODS: Fifty-nine SLE patients and 59 healthy, age-matched
      control subjects were studied. LDL size was determined by gradient gel
      electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene
      formation during copper incubation. Plasma levels of fasting insulin, glucose,
      lipids, lipoproteins, apolipoproteins B and A-I, and fatty acids were also
      measured. RESULTS: Compared with control subjects, SLE patients showed
      significantly higher plasma insulin levels and increased susceptibility of LDLs
      to oxidation. Patients with active disease were more likely than patients with
      inactive disease or control subjects to have the following lipid characteristics:
      small, dense LDL subclass, elevated total cholesterol levels, elevated LDL
      cholesterol levels, elevated triglyceride levels, and low levels of high-density
      lipoprotein cholesterol (HDL-C). Statistically significant direct correlations
      were observed between disease activity and triglyceride levels and between
      disease activity and lag time, whereas significant inverse correlations were
      found between disease activity and HDL-C levels and between disease activity and
      LDL size. Prednisone dosage explained only 15.6% of the variance in insulin
      levels. CONCLUSION: SLE patients have higher plasma insulin levels and increased
      LDL oxidizability compared with healthy control subjects. These abnormalities may
      contribute to the accelerated atherosclerosis observed in patients with SLE.

PMID- 14730613
TI  - Voiding dysfunction in women with systemic lupus erythematosus.
AB  - OBJECTIVE: We sought to explore bladder dysfunction in a cohort of women with
      systemic lupus erythematosus (SLE). METHODS: We conducted a prospective study of
      152 female patients with SLE during a 15-month period. The clinical status of SLE
      was determined according to the SLE Disease Activity Index (SLEDAI), and bladder
      function was evaluated by lower urinary tract symptoms and urodynamic studies. We
      adapted the American Urological Association (AUA) index questionnaire to assess
      lower urinary tract symptoms in patients, which were compared with those in 227
      age-matched healthy women. RESULTS: The proportion of individuals reporting
      urinary frequency, urgency, weak urinary stream, and incomplete emptying, as well
      as severe lower urinary tract symptoms (AUA index score >/=20), was significantly
      higher in the SLE group when compared with the control group. The AUA index score
      showed a modest correlation with the SLEDAI score (r = 0.35, P < 0.001) but not
      with patient age or disease duration. There was a significant relationship
      between central nervous system involvement and the AUA index score. The most
      common urodynamic finding was a small cystometric bladder capacity (<150 ml; n =
      7 patients), followed by a subnormal urinary flow rate (<12 ml/second; n = 6
      patients). In 3 of 7 patients with small cystometric bladder capacities, imaging
      studies documented a contracted bladder with marked hydroureteronephrosis.
      CONCLUSION: Patients with SLE experience an increased prevalence of voiding
      dysfunction compared with healthy individuals. Voiding dysfunction can be
      attributable to either direct bladder involvement or other disease-related
      factors.

PMID- 14730614
TI  - Immunohistologic evidence supports apoptosis, IgG deposition, and novel
      macrophage/fibroblast crosstalk in the pathologic cascade leading to congenital
      heart block.
AB  - OBJECTIVE: To assess in vivo the pathologic cascade leading to fibrosis in
      congenital heart block (CHB). In vitro studies suggest that CHB is initiated via
      apoptosis, resulting in translocation of SSA/Ro and SSB/La antigens and surface
      binding by maternal autoantibodies. These opsonized cardiocytes are phagocytosed
      by macrophages, which secrete factors inducing fibrosis. METHODS:
      Immunohistochemistry analysis was performed on formalin-fixed sections of 4 fetal
      hearts identified in utero as having CHB or isolated myocarditis; mothers had
      anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Apoptosis was most extensive in
      fetuses dying early and most pronounced in regions containing conduction tissue.
      Deposition of IgG was observed in hearts from fetuses with CHB/myocarditis, but
      not in 3 control hearts, and was colocalized with apoptotic cells. Giant cells
      and macrophages (frequently seen proximal to IgG and apoptotic cells) were
      present in septal and thickened fibrous subendocardial regions, most apparent in
      the youngest fetuses. Septal tissue also revealed extensive areas of fibrosis and
      microcalcification in which a predominant smooth muscle actin (SMA)-positive
      infiltrate (myofibroblast scarring phenotype) was observed. In contrast, there
      were no macrophages or SMA-positive cells (other than those lining blood vessels)
      in septal tissue from control hearts, although rare macrophages were seen in the
      working myocardium. CONCLUSION: In summary, findings in this unique autopsy
      material paralleled those in in vitro studies. These data support the notion of
      exaggerated apoptosis, probably due to ongoing inflammation caused by IgG binding
      and ingestion by macrophages. Transdifferentiation of cardiac fibroblasts to a
      scarring phenotype may be a pathologic process initiated by maternal antibodies,
      and persistence of this phenotype even after birth may relate to the progression
      of block seen in some infants postpartum.

PMID- 14730615
TI  - Ovarian vein thrombosis in the antiphospholipid syndrome.
AB  - Ovarian vein thrombosis (OVT) is an unusual condition mainly observed during the
      postpartum period. It has not been reported to date in the antiphospholipid
      syndrome. Two female patients with definite antiphospholipid syndrome, ages 33
      years and 73 years, were diagnosed as having OVT by computed tomography (CT)
      scan, according to the radiologic criteria described by Zerhouni et al. In 1 of
      the women, the left vein was affected by OVT, while in the other woman, the right
      vein was affected. One of the patients had a pulmonary embolism; the diagnosis of
      OVT was established after she underwent a cesarean section and a right atrium
      thrombectomy. The other patient had no vascular manifestations. OVT was
      asymptomatic in both patients. Searches for associated thrombophilic states
      yielded negative results. With the continuation of anticoagulation therapy, the 2
      patients have remained in good condition. Resolution of the OVT was observed in
      the patient who underwent a CT scan during followup. To our knowledge, this is
      the first report of OVT occurring in the antiphospholipid syndrome. Given that it
      may develop in the absence of pelvic clinical manifestations, this complication
      may be underdiagnosed.

PMID- 14730616
TI  - Genomic absence of the gene encoding T cell receptor Vbeta7.2 is linked to the
      presence of autoantibodies in Sjogren's syndrome.
AB  - OBJECTIVE: It is not yet known whether the absence of certain T cell receptor
      V(beta) (TCRBV) genes (e.g., due to genomic deletion) has functional
      significance. We examined this question in relation to a known 21.6-kb
      insertion/deletion-related polymorphism (IDRP) in the human BV locus. METHODS:
      New polymerase chain reaction (PCR) genotyping methods were used. Monoclonal
      antibodies to TCRBV gene products were used to confirm the absence of the
      relevant proteins. Patients with Sjogren's syndrome (SS) or systemic lupus
      erythematosus (SLE) were compared with normal controls with regard to TCR
      genotypes and serologic profiles. RESULTS: There are 3 known haplotypes (I, D1,
      D2) and 6 possible genotypes related to the 21.6-kb IDRP. Novel PCR-based methods
      were used to define these genotypes. In subjects with deleted/deleted (D/D)
      genotypes, T cells could not express V(beta)7.2 TCRs, as assayed with a new
      antibody specific for V(beta)7.2. This was the sole significant difference
      between subjects without the insertion and those with either 1 or 2 copies.
      Surprisingly, we found that the D/D genotype was associated with primary SS, but
      only when pathogenic autoantibodies were present. CONCLUSION: These results
      suggest that T cells expressing TCRs with V(beta)7.2 are protective against a
      pathogenic immune response in SS. Thus, genomic polymorphism of TCR genes (along
      with the correct HLA alleles) determines whether T cells can direct a pathogenic
      autoimmune response.

PMID- 14730617
TI  - Anatomic localization of immature and mature dendritic cell subsets in
      dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine
      producing cells.
AB  - OBJECTIVE: To clarify the involvement of dendritic cells (DCs), chemokines, and
      proinflammatory Th1 cytokines in the pathogenesis of the chronic muscle diseases
      dermatomyositis (DM) and polymyositis (PM). METHODS: We characterized by
      immunohistochemistry the DC subsets and their interaction with cells producing
      chemokines and the Th1 cytokines interleukin-17 (IL-17) and interferon-gamma
      (IFNgamma). Immature and mature DCs were defined by the expression of CD1a and DC
      LAMP/CD83, respectively. RESULTS: Immature DCs were mainly detected in
      lymphocytic infiltrates in DM and PM muscle tissue samples. Mature DCs were
      detected in perivascular infiltrates and surrounded muscle fibers. IL-17-positive
      and IFNgamma-positive cells were also observed in perivascular infiltrates in
      both cases. We then focused on the expression of the CCL20/CCR6
      chemokine/receptor complex, which controls immature DC migration, and on the
      expression of the CCL19/CCR7 and CCL21/CCR7 chemokine/receptor complexes, which
      control mature DC migration. CCL20 and CCR6 colocalized in lymphocytic
      infiltrates in DM and PM samples. CCL21 was rarely observed in DM samples and
      never observed in PM samples. CCL19- and CCR7-expressing cells were absent in
      both tissues. CONCLUSION: The close association between CCL20/CCR6 and immature
      DCs suggests the contribution of CCL20 to CCR6+ immature DC homing. Detection of
      mature DCs in DM and PM muscle tissue samples despite the lack of CCL19 and CCR7
      is evidence for a local maturation of DCs in inflammatory muscle tissue without
      lymphoid organ organization.

PMID- 14730618
TI  - Anti-signal recognition particle autoantibody in patients with and patients
      without idiopathic inflammatory myopathy.
AB  - OBJECTIVE: To determine the long-term outcome and associated clinical, serologic,
      and pathologic features in a cohort of patients with connective tissue disease
      (CTD) and the anti-signal recognition particle (anti-SRP) autoantibody. METHODS:
      Sera and clinical data were collected prospectively from consecutive adult
      patients with polymyositis (PM; n = 134), dermatomyositis (n = 129), or other
      CTDs (predominantly systemic sclerosis [SSc; n = 790]). Patients were first
      evaluated during 1973-2001. RESULTS: Nineteen patients with the anti-SRP
      autoantibody were identified, 16 (84%) of whom had pure PM and 3 (2 with SSc and
      1 with antisynthetase syndrome) had yet to develop features of myositis after a
      mean followup of 4.5 years (range 2.5-6 years). More SRP-positive PM patients had
      severe proximal muscle weakness (50%) and muscle atrophy (67%) at initial
      presentation compared with antisynthetase-positive PM controls. Cardiac
      involvement occurred in only 2 of 16 SRP-positive PM patients (13%), and
      interstitial lung disease was noted in 3 of 13 SRP-positive PM patients (23%) and
      in the 3 SRP-positive nonmyositis patients. There was a relative lack of
      inflammation in muscle biopsy specimens from the SRP-positive PM cohort. Other
      autoantibodies in the SRP-positive patients included Ro/SSA (4 patients), Th/To
      (1 patient), and anti-PL-12 (1 patient). Survival in the SRP-positive PM patients
      was comparable with that seen in the cohort of SRP-negative PM patients.
      CONCLUSION: The anti-SRP autoantibody is not specific for PM. Severe muscle
      weakness and atrophy were prominent features in PM patients with anti-SRP.
      Cardiac involvement was less common and survival was better in patients with anti
      SRP than has previously been reported.

PMID- 14730619
TI  - Angiotensin II in the lesional skin of systemic sclerosis patients contributes to
      tissue fibrosis via angiotensin II type 1 receptors.
AB  - OBJECTIVE: Tissue fibrosis in systemic sclerosis (SSc) is attributed to excessive
      deposition of extracellular matrix components produced by fibroblasts in skin
      lesions. Angiotensin II (Ang II), a vasoconstrictive peptide, is reported to have
      profibrotic activity as a result of induction of the extracellular matrix. The
      aim of the present study was to examine the expression of Ang II and its type 1
      (AT(1)) and type 2 (AT(2)) receptors in affected skin and dermal fibroblasts from
      patients with SSc and to study the role of Ang II in collagen production by SSc
      dermal fibroblasts. METHODS: Levels of Ang II in sera from SSc patients and
      normal subjects were measured by a solid-phase immobilized-epitope immunoassay.
      Expression of angiotensinogen (Angt) in the skin was evaluated by
      immunohistochemistry. Expression of Angt, AT(1), and AT(2) in cultured dermal
      fibroblasts was analyzed by reverse transcription-polymerase chain reaction and
      immunohistochemistry. Levels of type I procollagen produced by cultured dermal
      fibroblasts were measured by enzyme-linked immunosorbent assay. RESULTS: Serum
      Ang II levels in patients with diffuse cutaneous SSc were significantly higher
      than those in patients with limited cutaneous SSc and in healthy donors.
      Immunohistochemical and immunoblotting analyses showed that Angt was present in
      skin from SSc patients, but not in normal skin. Angt messenger RNA (mRNA) was
      expressed in fibroblasts from patients with diffuse cutaneous SSc who had high
      levels of serum Ang II, but not in normal fibroblasts. AT(1) mRNA expression was
      found in both SSc and normal fibroblasts, whereas AT(2) mRNA was found only in
      SSc fibroblasts. Exogenous Ang II augmented the production of type I procollagen
      and transforming growth factor beta1 by cultured fibroblasts via activation of
      AT(1). CONCLUSION: Aberrant Ang II production may be involved in tissue fibrosis
      through excessive production of the extracellular matrix components in SSc dermal
      fibroblasts. This suggests that the use of AT(1) receptor antagonists may be a
      novel strategy for the treatment of tissue fibrosis in SSc patients.

PMID- 14730620
TI  - Anti-DNA topoisomerase IIalpha autoantibodies in localized scleroderma.
AB  - OBJECTIVE: To determine the prevalence and clinical correlation of anti-DNA
      topoisomerase IIalpha (anti-topo IIalpha) antibody in patients with localized
      scleroderma. METHODS: Anti-topo IIalpha antibodies or anti-DNA topoisomerase I
      (topo I) antibodies were determined by enzyme-linked immunosorbent assay (ELISA)
      and immunoblotting. Inhibition of topo IIalpha enzymatic activity by the
      antibodies was evaluated by decatenation assays using kinetoplast DNA as a
      substrate. RESULTS: IgG or IgM anti-topo IIalpha antibody was detected in 76% (35
      of 46) of patients with localized scleroderma, and in 85% (11 of 13) of patients
      with generalized morphea, the severest form of localized scleroderma. This
      prevalence of the antibody in patients with localized scleroderma was much higher
      than that found in patients with systemic sclerosis (SSc) (5 of 37 [14%]),
      systemic lupus erythematosus (2 of 26 [8%]), dermatomyositis (2 of 20 [10%]), and
      in healthy controls (3 of 42 [7%]). Immunoblotting confirmed the presence of IgG
      anti-topo IIalpha antibody in sera from patients with localized scleroderma and
      showed no cross-reactivity of anti-topo IIalpha antibody with topo I. Anti-topo I
      antibody was not detected by ELISA in any sera from patients with localized
      scleroderma. In addition, anti-topo I antibody from SSc patients did not cross
      react with topo IIalpha. The presence of anti-topo IIalpha antibody was
      associated with a greater total number of sclerotic lesions and number of plaque
      lesions in patients with localized scleroderma. Furthermore, anti-topo IIalpha
      antibody was able to inhibit topo IIalpha enzymatic activity. CONCLUSION: The
      results of the present study indicate that anti-topo IIalpha is a major
      autoantibody in localized scleroderma, and is distinct from anti-topo I antibody
      in SSc.

PMID- 14730621
TI  - Selective cleavage of nucleolar autoantigen B23 by granzyme B in differentiated
      vascular smooth muscle cells: insights into the association of specific
      autoantibodies with distinct disease phenotypes.
AB  - OBJECTIVE: To investigate the association of specific autoantibodies with
      distinct disease phenotypes. The association of autoantibodies to
      nucleophosmin/B23 with pulmonary hypertension in scleroderma, and the
      susceptibility of autoantigens to cleavage by granzyme B (GB), provided a focus
      for these studies. METHODS: Intact cells were subjected to cytotoxic lymphocyte
      granule-induced death, and the susceptibility of autoantigens to cleavage by GB
      was addressed by immunoblotting and/or by a novel immunofluorescence assay.
      RESULTS: B23 was cleaved efficiently by GB in vitro, but was highly resistant to
      cleavage by GB during cytotoxic lymphocyte granule-mediated death of many intact
      cell types. In contrast, this molecule was highly susceptible to GB-mediated
      proteolysis exclusively in differentiated vascular smooth muscle cells.
      Topoisomerase I and several other GB substrates did not show this striking change
      in cleavage susceptibility in different cell types. CONCLUSION: These data
      demonstrate that the cleavage of B23 by GB in intact cells is dependent upon both
      cell type and phenotype. The susceptibility of this autoantigen (which is
      associated with a distinct pulmonary vascular phenotype in scleroderma) to GB
      mediated proteolysis selectively in vascular smooth muscle cells suggests that
      the GB-cleavable conformation of autoantigens may occur selectively in the target
      tissue, and may play a role in shaping the phenotype-specific autoimmune
      response.

PMID- 14730622
TI  - Complex segregation and linkage analysis of familial gout in Taiwanese
      aborigines.
AB  - OBJECTIVE: The prevalence of gout and hyperuricemia in Taiwanese aborigines is
      remarkably high. Although previous studies have failed to find evidence of a
      major gene responsible for gout, the disease is thought to involve genetic
      predisposition. We sought to determine whether genetic factors for familial gout
      exist among Taiwanese aborigines, and, if so, their chromosomal location.
      METHODS: We first performed complex segregation analysis. The study sample
      comprised 945 relatives distributed in 64 pedigrees; among them, 261 affected
      members (including probands) were found. In all of the aboriginal probands with
      gout, the disease was diagnosed and confirmed by rheumatologists. Blood specimens
      were then collected from 127 individuals living in one community that was used in
      the segregation analysis (from 25 pedigrees, 36 nuclear families, and 112 full
      sibpairs), and sibpair linkage analysis and a combined transmission
      disequilibrium test (TDT) method were used to test the genetic components.
      RESULTS: In segregation analysis, after adjusting for sex and age, an autosomal
      arbitrary major gene model was found to fit the data best, with disease allelic
      frequency of 0.31 and susceptibility of 0.92. In sibpair analysis, there was a
      clustering of many flanking markers showing significant linkage, including D1S498
      (regression coefficient -0.52), D1S2635 (regression coefficient -0.47), and
      D1S196 (regression coefficient -0.51), in the 1q21 region of chromosome 1 (all P
      < 0.005). Results of the combined TDT showed that the marker D1S484 was
      significantly associated (had linkage) with allele 1 and was transmitted more
      frequently than other markers to the affected offspring (P < 0.005). CONCLUSION:
      Results of this study provide evidence of a genetic basis for familial gout in
      the aboriginal Taiwanese population and suggest that a susceptibility locus may
      be located in the 1q21 region of chromosome 1.

PMID- 14730623
TI  - Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium
      urate crystal-induced nitric oxide production and matrix metalloproteinase 3
      expression in chondrocytes.
AB  - OBJECTIVE: Articular deposition of monosodium urate monohydrate (MSU) crystals
      may promote cartilage and bone erosion. Therefore, the aim of this study was to
      determine how MSU crystals stimulate chondrocytes. METHODS: Nitric oxide (NO)
      release, and expression of inducible nitric oxide synthase (iNOS) and matrix
      metalloproteinase 3 (MMP-3) were assessed in cultured chondrocytes treated with
      MSU. MSU-induced functional signaling by specific protein kinases (p38, Src, and
      the focal adhesion kinase [FAK] family members proline-rich tyrosine kinase 2
      [Pyk-2] and FAK) was also examined using selective pharmacologic inhibitors and
      transfection of kinase mutants. RESULTS: MSU induced MMP-3 and iNOS expression
      and NO release in chondrocytes in a p38-dependent manner that did not require
      interleukin-1 (IL-1), as demonstrated by using IL-1 receptor antagonist. MSU
      induced rapid tyrosine phosphorylation of Pyk-2 and FAK, their adaptor protein
      paxillin, and interacting kinase c-Src. Pyk-2 and c-Src signaling both mediated
      p38 MAPK activation in response to MSU. Pyk-2 and c-Src signaling played a major
      role in transducing MSU-induced NO production and MMP-3 expression. But, despite
      the observed FAK phosphorylation, a selective pharmacologic FAK inhibitor and a
      FAK dominant-negative mutant both failed to block MSU-induced NO release or MMP-3
      expression in parallel experiments. CONCLUSION: In chondrocytes, MSU crystals
      activate a signaling kinase cascade typically employed by adhesion receptors that
      involves upstream Src and FAK family activation and downstream p38 activation. In
      this cascade, Pyk-2, Src, and p38 kinases transduce MSU-induced NO production and
      MMP-3 expression. Our results identify Pyk-2 and c-Src as novel sites for
      potential therapeutic intervention in cartilage degradation in chronic gout.

PMID- 14730624
TI  - Emergence of lyme arthritis after autologous chondrocyte transplantation.
AB  - We report herein the first known incidence of the emergence of borrelial
      arthritis following autologous chondrocyte transplantation for repair of a
      cartilage defect. The patient had no recent manifestation of Lyme borreliosis,
      but 15 years earlier had had an expanding erythematous lesion after a tick bite.
      The current infection resulted in massive joint swelling, elevated body
      temperature, dissemination of the graft, and transplant failure. Results of
      routine bacteriologic studies were negative. A diagnosis of Lyme arthritis was
      first considered following the detection of Borrelia-specific serum antibodies.
      Additional evidence was provided when borrelial DNA sequences were detected in
      the synovial fluid through polymerase chain reaction. The diagnosis was confirmed
      by culture of Borrelia burgdorferi from the synovial fluid. The possibility of a
      dormant borrelial infection should be considered in patients who undergo repair
      of cartilage defects with autologous chondrocyte transplantation. We recommend
      that synovial fluid and joint tissue be screened for the presence of viable
      Borrelia before transplantation of an autologous graft.

PMID- 14730625
TI  - Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh
      osteoclast precursors in tumor necrosis factor alpha-transgenic mice.
AB  - OBJECTIVE: To investigate the mechanisms whereby tumor necrosis factor alpha
      (TNFalpha) increases osteoclastogenesis in vivo. METHODS: TNFalpha-transgenic
      (TNF-Tg) and wild-type mice injected with TNFalpha were studied. In vitro
      osteoclastogenesis assays, monocyte colony-forming assays, and fluorescence
      activated cell sorting were performed using splenocytes, peripheral blood
      mononuclear cells (PBMCs), and bone marrow cells to quantify and characterize
      osteoclast precursors (OCPs). Etanercept, a TNFalpha antagonist, was used to
      block TNFalpha activity in vivo. The effects of TNFalpha on proliferation,
      apoptosis, and differentiation of OCPs were assessed using 5-bromo-2'
      deoxyuridine labeling, annexin V staining, and reverse transcriptase-polymerase
      chain reaction. RESULTS: OCP numbers were increased 4-7-fold in PBMCs and spleen,
      but not in bone marrow of TNF-Tg mice. The OCPs in spleen were in the CD11b(high)
      population and contained both c-Fms- and c-Fms+ cells. The increased number of
      OCPs correlated with the initiation of detectable TNFalpha in serum and the onset
      of inflammatory arthritis in TNF-Tg mice. Etanercept eliminated the increase in
      peripheral OCPs. TNFalpha did not affect proliferation, survival, or
      differentiation of CD11b(high) splenocytes in vivo or in vitro, but caused a
      rapid increase in CD11b+ cells in blood within 4 hours of a single injection and
      an accumulation of CD11b(high) OCPs in spleen after 3 days of multiple
      injections. CONCLUSION: Systemic TNFalpha induces a marked increase in
      circulating OCPs that is reversible by anti-TNF therapy and may result from their
      mobilization from bone marrow. Our findings provide a new mechanism whereby
      TNFalpha stimulates osteoclastogenesis in patients with inflammatory arthritis,
      suggesting that CD11b+ PBMCs could be used to evaluate a patient's potential for
      erosive disease and the efficacy of anti-TNF therapy.

PMID- 14730627
TI  - The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in
      the hypoxic synovium of inflamed joints in adjuvant-induced arthritis.
AB  - OBJECTIVE: To determine the relationship between hypoxia and the expression of
      Ets-1 and hypoxia-inducible factor 1alpha (HIF-1alpha) in both normal and
      inflamed joints. Adjuvant-induced arthritis (AIA) was used as the model system,
      since it mirrors many aspects of the pathology of rheumatoid arthritis. METHODS:
      Adjuvant arthritis was induced in a group of 10 female Lewis rats. A second group
      of 10 uninjected female Lewis rats served as naive controls. When a maximum
      clinical joint score was achieved in the AIA group, all 20 rats were injected
      with the specific hypoxic cell marker Hypoxyprobe-1 and subsequently killed.
      Hypoxyprobe-1 adducts, Ets-1, and HIF-1alpha were localized in the joints of the
      hind feet from these groups using immunohistochemistry. RESULTS: Compared with
      the joints from control rats, inflamed joints contained markedly more cells with
      Hypoxyprobe-1 adduct immunoreactivity, Ets-1-immunoreactive nuclei, and nuclear
      immunoreactivity for both Ets-1 and HIF-1alpha. CONCLUSION: Our results
      demonstrate the presence of hypoxia in inflamed joints in this experimental model
      of arthritis. The colocalization of Ets-1 and HIF-1alpha in these hypoxic areas
      suggests that hypoxia may induce Ets-1 and HIF-1alpha expression during joint
      inflammation.

PMID- 14730626
TI  - Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL
      pathways in tumor necrosis factor-induced arthritis: effects on synovial
      inflammation, bone erosion, and cartilage destruction.
AB  - OBJECTIVE: To investigate the efficacy of single and combined blockade of tumor
      necrosis factor (TNF), interleukin-1 (IL-1), and RANKL pathways on synovial
      inflammation, bone erosion, and cartilage destruction in a TNF-driven arthritis
      model. METHODS: Human TNF-transgenic (hTNFtg) mice were treated with anti-TNF
      (infliximab), IL-1 receptor antagonist (IL-1Ra; anakinra), or osteoprotegerin
      (OPG; an OPG-Fc fusion protein), either alone or in combinations of 2 agents or
      all 3 agents. Synovial inflammation, bone erosion, and cartilage damage were
      evaluated histologically. RESULTS: Synovial inflammation was inhibited by anti
      TNF (-51%), but not by IL-1Ra or OPG monotherapy. The combination of anti-TNF
      with either IL-1Ra (-91%) or OPG (-81%) was additive and almost completely
      blocked inflammation. Bone erosion was effectively blocked by anti-TNF (-79%) and
      OPG (-60%), but not by IL-1Ra monotherapy. The combination of anti-TNF with IL
      1Ra, however, completely blocked bone erosion (-98%). Inhibition of bone erosion
      was accompanied by a reduction of osteoclast numbers in synovial tissue.
      Cartilage destruction was inhibited by anti-TNF (-43%) and was weakly, but not
      significantly, inhibited by IL-1Ra, but was not inhibited by OPG monotherapy. The
      combination of anti-TNF with IL-1Ra was the most effective double combination
      therapy in preventing cartilage destruction (-80%). In all analyses, the triple
      combination of anti-TNF, IL-1Ra, and OPG was not superior to the double
      combination of anti-TNF and IL-1Ra. CONCLUSION: Articular changes caused by
      chronic overexpression of TNF are not completely blockable by monotherapies that
      target TNF, IL-1, or RANKL. However, combined approaches, especially the combined
      blockade of TNF and IL-1 and, to a lesser extent, TNF and RANKL, lead to almost
      complete remission of disease. Differences in abilities to block synovial
      inflammation, bone erosion, and cartilage destruction further strengthen the
      rationale for using combined blockade of more than one proinflammatory pathway.

PMID- 14730628
TI  - Oligodeoxynucleotides containing CpG motifs can induce T cell-dependent arthritis
      in rats.
AB  - OBJECTIVE: To investigate whether CpG oligodeoxynucleotides (ODNs) can induce or
      accelerate arthritis in rats. METHODS: The CpG-induced response was studied by
      recording joint inflammation, cell activation in draining lymph nodes, and levels
      of the acute-phase reactant alpha(1)-acid glycoprotein (AGP) in sera. The role of
      T cells was investigated by in vivo administration of monoclonal antibodies
      specific for the T cell receptor alpha/beta (TCRalpha/beta), followed by analysis
      of cell phenotypes by flow cytometry. RESULTS: One intradermal injection of CpG
      ODN emulsified with Freund's incomplete adjuvant (IFA) induced arthritis in LEW
      and LEW.1AV1 rats, while the control ODN sequence without CpG motifs or IFA alone
      did not trigger disease. The CpG/IFA and control-ODN/IFA injections induced
      lymphoplasia as well as elevated levels of interleukin-1beta and interferon-gamma
      messenger RNA in lymph nodes. The arthritis was preceded by elevated levels of
      AGP in serum. In vivo administration of anti-TCRalpha/beta antibodies after
      disease induction caused decreased expression of the TCR-CD3 complex on
      circulating T cells and ameliorated the arthritis. CONCLUSION: We demonstrated
      that injection with immunostimulatory CpG, both in phosphorothioate-modified and
      native forms, can induce a T cell-dependent joint-specific inflammation in LEW
      and LEW.1AV1 rat strains. This arthritis is preceded by signs of activation of
      the innate immune system. Since unmethylated CG dinucleotides are common in
      bacterial DNA but rare in mammalian DNA, our results indicate that exposure to
      bacterial DNA during infection may contribute to arthritis induction by
      amplifying the innate immune response.

PMID- 14730629
TI  - Suppression of collagen-induced arthritis by natural killer T cell activation
      with OCH, a sphingosine-truncated analog of alpha-galactosylceramide.
AB  - OBJECTIVE: OCH, a synthetic analog of alpha-galactosylceramide with a truncated
      sphingosine chain, stimulates natural killer T (NKT) cells to produce
      predominantly Th2 cytokines. Thus, OCH may be a potential agent for the treatment
      of Th1-mediated autoimmune diseases. This study was designed to evaluate the
      protective effects of OCH on collagen-induced arthritis (CIA) in mice. METHODS:
      Mice were immunized with type II collagen (CII) and injected intraperitoneally
      twice per week with OCH, before or after the onset of CIA. They were monitored to
      assess the effect of OCH treatment on the severity of disease. Anti-CII
      antibodies and cytokine production were measured by enzyme-linked immunosorbent
      assay. Expression of cytokine genes was determined by quantitative reverse
      transcriptase-polymerase chain reaction. RESULTS: OCH inhibited CIA in wild-type
      C57BL/6 (B6) mice but not in NKT-deficient mice. OCH suppressed CIA in SJL mice,
      which are prone to autoimmune diseases and have a deficiency in the number and
      function of NKT cells which is similar to that in patients with autoimmune
      diseases, even after disease has already developed. Disease protection conferred
      by OCH correlated with its ability to selectively induce Th2 cytokine production
      mediated by NKT cells and to promote collagen-specific Th2 responses.
      Neutralization of interleukin-4 (IL-4) or IL-10 with monoclonal antibodies
      abolished disease protection by OCH, indicating a critical role for these
      cytokines. CONCLUSION: Taken together, our findings suggest that OCH holds
      possibilities as a therapeutic agent for autoimmune diseases such as rheumatoid
      arthritis.

PMID- 14730630
TI  - Effects of different molecular weight elastoviscous hyaluronan solutions on
      articular nociceptive afferents.
AB  - OBJECTIVE: To compare 3 different hyaluronan (HA) preparations used as
      therapeutic agents for osteoarthritis pain in humans in order to establish the
      degree to which a single application affects the sensitivity of nociceptors in
      both the normal and the acutely inflamed rat joint. METHODS: In anesthetized
      rats, single-unit recordings were performed from the medial articular nerve of
      the right knee joint under normal conditions and during an acute experimental
      arthritis. Fifty fine afferent units (conduction velocities 0.8-15.3
      meters/second) responded to passive movements of the knee joint. They were
      exposed to a torque meter-controlled, standardized stimulus protocol consisting
      of innocuous and noxious inward and outward rotations of the joint. This stimulus
      protocol of 50 seconds' duration was repeated every 5 minutes for 2-3 hours.
      Three commercially available HA preparations and a buffer solution, the solvent
      of these preparations, were injected intraarticularly after discharges resulting
      from 6 stimulus protocols were averaged and used as controls. RESULTS: Both in
      normal and in inflamed joints, the injection of Hyalgan did not reduce nerve
      impulse frequency of the evoked discharges. The injections of Orthovisc had no
      effect in normal joints, but produced a transient frequency reduction of the
      evoked discharge in inflamed joints. Synvisc significantly reduced (by an average
      of 50%) the impulse discharge in both normal and inflamed joints 50 minutes after
      injection, and this level of impulse discharge continued until the end of the
      recording period (120-130 minutes after injection). The buffer, which had
      elastoviscous properties substantially different from those of Hyalgan,
      Orthovisc, and Synvisc, had no such effect. CONCLUSION: We conclude that the
      elastoviscous properties of HA solutions are determining factors in reducing pain
      eliciting nerve activity both in normal and in inflamed rat joints.

PMID- 14730632
TI  - A CTLA-4 polymorphism associated with susceptibility to systemic lupus
      erythematosus.

PMID- 14730631
TI  - The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus
      nephritis.

PMID- 14730633
TI  - Fibrillin 1 abnormalities in dermal fibroblast cultures from first-degree
      relatives of patients with systemic sclerosis (scleroderma).

PMID- 14730634
TI  - Validation of a computer version of the American College of Rheumatology patient
      assessment questionnaire for the autonomous self-entry of self-report data in an
      urban rheumatology clinic.

PMID- 14730635
TI  - A brief history of Wegener's granulomatosis: on limited, localized, and
      generalized forms of the disease: comment on the article by the Wegener's
      Granulomatosis Etanercept Trial Research Group.

PMID- 14730637
TI  - Leflunomide and anti-glomerular basement membrane glomerulonephritis: comment on
      the letter by Bruyn et al.

PMID- 14730639
TI  - Intravenous immunoglobulin and placental transport of anti-Ro/La antibodies:
      comment on the letter by Kaaja and Julkunen.

PMID- 14730644
TI  - Obituary: Lucile E. St. Hoyme (1924-2001).

PMID- 14730641
TI  - Ultrasound-guided steroid injections in the treatment of hip osteoarthritis:
      comment on the letter by Margules.

PMID- 14730645
TI  - Influence of Plio-Pleistocene aridification on human evolution: evidence from
      paleosols of the Turkana Basin, Kenya.
AB  - New stable carbon isotope measurements, coupled with paleoprecipitation
      estimates, both from Plio-Pleistocene paleosols of the Turkana Basin, Kenya,
      provide a high-resolution record of aridification and increasing C4 biomass
      during the past 4.3 Ma. This aridification trend is marked by several
      punctuations at 3.58-3.35, 2.52-2, and 1.81-1.58 Ma, during which the running
      mean and variance of delta13C and paleoaridity estimates increase, suggesting
      that the proportion of C4 biomass increases in savanna mosaics during periods of
      heightened aridity. Increase in C4 biomass during these aridification events not
      only increases the proportion of open habitats, but increases the spatial neg
      entropy, or heterogeneity of the ecosystem. The aridification events identified
      correspond to intervals of increased turnover, but more importantly, increased
      diversity of bovids. Although the record of hominins from the Turkana Basin lacks
      the temporal resolution and diversity of the bovid record, the aridification
      intervals identified are marked by similar increases in the diversity and
      turnover of hominins. These results support the hypothesis that hominins evolved
      in savanna mosaics that changed through time, and suggest that the evolution of
      bovids and hominins was driven by shifts in climatic instability and habitat
      variability, both diachronic and synchronic.

PMID- 14730646
TI  - Tooth cementum annulation for age estimation: results from a large known-age
      validation study.
AB  - Recent research indicates that tooth-cementum annulations (TCA) may be used more
      reliably than other morphological or histological traits of the adult skeleton to
      estimate age. Until now, however, confidence intervals for age estimated by this
      method have not been available for paleodemographic and forensic applications.
      The present study addresses this problem. Based on a large known-age sample, age
      estimates by TCA were conducted in a blind study involving 363 teeth. Tooth-root
      cross sections were made using a refined preparation technique. Improved digital
      graphic procedures and enhancement strategies were used to produce digital images
      with a specially adapted software package. This resulted in high concordance
      between the TCA age estimates and chronological age. Assessment of the method's
      accuracy, as expressed by 95% confidence intervals, showed that error bounds for
      age estimates do not exceed 2.5 years. Sex differences, intraindividual
      correlations, and the effects of periodontal disease were studied. None of these
      indicators had a quantitative effect on the number of TCA bands when the proposed
      methodological standard was followed. We conclude that the TCA technique is a
      reliable method for estimating a subject's age from cementum annulations.

PMID- 14730647
TI  - Nonmetric cranial trait variation and prehistoric biocultural change in the Azapa
      Valley, Chile.
AB  - Historically, interpretations of both biological and cultural change within the
      prehistoric Azapa Valley, northern Chile, have cited large-scale population
      movements, with replacement from complex societies located in the adjacent
      highlands to the east. Biological estimates of this change have traditionally
      relied upon biodistance estimates, using craniofacial measures of both deformed
      and nondeformed skulls. In order to evaluate whether large-scale prehistoric
      migrations occurred in the Azapa Valley, we examine biodistance results from
      nonmetric cranial traits for eight mortuary samples that represent all time
      periods of prehistoric occupation of the valley. None of the mean measures of
      divergences (MMD) among mortuary samples examined by this study were significant.
      These results suggest biological continuity in the Azapa Valley during 5,000
      years of prehistory, with nonsignificant gene flow during the late Middle Horizon
      (AD 750-1100) and Late Intermediate (AD 1100-1476) periods. Biodistance results
      also suggest endogamy within coastal and inland populations. The broader
      implications of these results are discussed.

PMID- 14730648
TI  - Effects of different kinds of cranial deformation on the incidence of wormian
      bones.
AB  - Researchers have debated whether the presence and frequency of wormian bones
      (sutural bones, supernumerary bones, and ossicles) are attributable to genetic
      factors, environmental factors, or both. This research examines the effects of
      many different kinds of cranial deformation on the incidence of wormian bones. A
      sample of 127 deformed and undeformed crania from New World archaeological sites
      was examined. An undeformed cranial sample (n=35) was compared to the following
      cranially deformed groups: 1) occipital, 2) lambdoid, 3) annular, 4) fronto
      vertico-occipital, 5) parallelo-fronto-occipital, and 6) sagittal synostosis.
      Three levels of degree of cultural cranial deformation were qualitatively
      determined. Type and number of wormian bones along each major suture were
      recorded for each cranium. Group means were analyzed using Kruskal-Wallis one-way
      ANOVA statistical tests to test the null hypothesis that cranial deformation does
      not have an effect on wormian bone incidence. Results indicate that all forms of
      cranial deformation affect the frequency of some types of wormian bones. In
      particular, all cranially deformed groups exhibited significantly greater
      frequencies of lambdoid ossicles. Apical, parieto-mastoid, and occipito-mastoid
      wormian bones also appeared with greater frequency in some groups of culturally
      deformed crania. Further, varying degrees of cultural deformation all had more
      lambdoid wormian bones than the undeformed group. These results suggest that
      wormian bone development in posteriorly placed sutures may be affected more by
      environmental forces than are their anteriorly placed counterparts.

PMID- 14730649
TI  - Predicting long bone loading from cross-sectional geometry.
AB  - Long bone loading histories are commonly evaluated using a beam model by
      calculating cross-sectional second moments of areas (SMAs). Without in vivo
      strain data, SMA analyses commonly make two explicit or implicit assumptions.
      First, while it has long been known that axial compression superimposed on
      bending shifts neutral axes away from cross-sectional area centroids, most
      analyses assume that cross-sectional properties calculated through the area
      centroid approximate cross-sectional strength. Second, the orientation of maximum
      bending rigidity is often assumed to reflect the orientation of peak or habitual
      bending forces the bone experiences. These assumptions are tested in sheep in
      which rosette strain gauges mounted at three locations around the tibia and
      metatarsal midshafts measured in vivo strains during treadmill running at 1.5
      m/sec. Calculated normal strain distributions confirm that the neutral axis of
      bending does not run through the midshaft centroid. In these animals,
      orientations of the principal centroidal axes around which maximum SMAs (Imax)
      are calculated are not in the same planes in which the bones experienced bending.
      Cross-sectional properties calculated using centroidal axes have substantial
      differences in magnitude (up to 55%) but high correlations in pattern compared to
      cross-sectional properties calculated around experimentally determined neutral
      axes. Thus interindividual comparisons of cross-sectional properties calculated
      from centroidal axes may be useful in terms of pattern, but are subject to high
      errors in terms of absolute values. In addition, cross-sectional properties do
      not necessarily provide reliable data on the orientations of loads to which bones
      are subjected.

PMID- 14730650
TI  - Variation in crown and root formation and eruption of human deciduous teeth.
AB  - The aim of this study was to document variation of deciduous tooth formation and
      eruption. The material comprises 121 individuals of known or estimated age (using
      tooth length) from Spitalfields in London, and radiographs of 61 healthy living
      children aged 2-5 years. Other skeletal material from two medieval Scottish
      archaeological sites (Whithorn, N=74; Newark Bay, N=59) was also examined. Stages
      of crown and root formation as well as eruption (alveolar, midway, and occlusal
      levels) were assessed for each developing maxillary and mandibular tooth from
      radiographs or direct vision. Age of attainment for individual stages was
      calculated by probit analysis, and these data were also adapted for use in
      estimating age. The timing of crown completion was similar to previously reported
      studies, but apex completion times were later. Analysis of data relative to the
      first and second molars at the two stages D (crown complete) and F (root length >
      or =crown height) allowed comparison with the Scottish material. No significant
      differences were observed between population groups for tooth formation or
      eruption. These data fill several gaps in the literature, and will be useful in
      assessing maturity and predicting age during early childhood.

PMID- 14730651
TI  - Multivariate analysis of organismal and habitat parameters in two neotropical
      primate communities.
AB  - This paper investigates the interrelations of some organismal and habitat
      parameters in two platyrrhine primate communities in French Guiana and Ecuadorian
      Amazonia. Fifteen habitat and organismal parameters and body weight were retained
      after a preliminary analysis, on the basis of frequent use and constraints
      reflected in anatomical specializations. The 16 parameters for 13 platyrrhine
      species were used for a series of principal components analyses (PCAs). All PCAs
      on separate or combined communities provided comparable results. The Atelinae,
      Ateles, Alouatta, and Lagothrix, were clustered together with Pithecia,
      associated with canopy, mature forest, frugivory, and (to a lesser degree)
      climb/suspensory locomotion. On the other hand, the three species of Cebus
      usually formed a loose cluster, located in the center of the cloud of species.
      Lastly, the Callitrichinae, involving two species of Saguinus and Cebuella, were
      relatively dispersed and frequently associated with liana forest, lianas,
      understory, and faunivory. However, Cebuella was consistently isolated and
      associated with liana forest, lianas, body weight, understory, and vertical
      supports. In this way, clusters appeared to conform to the major platyrrhine
      taxonomic groups, supporting the fact that basic ecological and behavioral
      adaptations have evolved in a phylogenetic context. In addition, the analyses
      revealed that body weight, forest type and layer, feeding behavior, and
      locomotion are the most important variables that have apparently shaped or driven
      the adaptive zones of extant platyrrhines.

PMID- 14730652
TI  - Bringing new treatments to the bedside in cystic fibrosis.
AB  - The discovery of the cystic fibrosis transmembrane conductance regulator gene in
      1989 led to a dramatic increase in the understanding of the molecular basis of
      CF. Increased knowledge has provided the opportunity to target drug development
      at correcting the basic defect either by gene therapy or pharmacological
      modulation of the abnormal physiological processes. Development of new
      medications for the CF population poses many challenges. The discovery and
      development of new medications is always time consuming and expensive. Since CF
      affects a small population worldwide, the potential for a drug company to profit
      from a new treatment is limited. In addition, each new therapy must have an
      additional and proven benefit to be attractive to clinicians and consumers,
      otherwise it will not be commercially viable. Demonstrating clinical benefit is
      problematic as a limited number of patients are available to participate in
      clinical trails and outcome measures, such as length of life, are hard to
      measure. In this review we will illustrate these challenges by discussing the
      development of treatments which have successfully reached the bedside and those
      that were unsuccessful.

PMID- 14730653
TI  - Pulmonary effects of gastroschisis in a fetal rabbit model.
AB  - Respiratory insufficiency is a significant cause of mortality and morbidity among
      infants with anterior abdominal wall defects (AWD). The aim of this study was to
      evaluate the pulmonary effects in a fetal rabbit model where gastroschisis was
      induced at midgestation. Gastroschisis (GAS) was created in 20 rabbit fetuses on
      day 22 or 23 of gestation (pseudoglandular phase; term = 31-32 days). The
      amniotic sacs of 13 fetuses were subjected to hysterotomy and amniotomy only
      (HYST), while 13 underwent a sham laparotomy which was immediately closed by
      sutures (SHAM). Eleven nonoperated littermates served as internal controls (CTR).
      Fetuses were harvested by cesarean section on day 31 of gestation prior to
      respiration. Pulmonary response was evaluated by left lung to body weight ratio
      (LWBWR), airway morphometry, and density of type II pneumocytes, as evaluated by
      the number of surfactant protein B-positive cells. Fetuses from the GAS group had
      significantly lower body weights than did CTR (P = 0.0129). Of these fetuses, 27%
      were growth-restricted, i.e., with a body weight under the 10th percentile of the
      CTR population. There were no differences in left lung weight and LWBWR among the
      GAS and CTR groups. Moreover, the GAS group had similar alveolar size, alveolar
      wall thickness, and type II cell density as CTR fetuses. Only mean terminal
      bronchiolar density (MTBD), which is inversely related to the alveolar space, was
      slightly increased in the GAS group, but without reaching significance (P =
      0.0821). No effect on lung growth and maturation could be demonstrated in this
      study.

PMID- 14730654
TI  - Reduction in prevalence of chronic Pseudomonas aeruginosa infection at a regional
      pediatric cystic fibrosis center.
AB  - Various management strategies were introduced at the Leeds Regional Cystic
      Fibrosis (CF) Unit in an attempt to reduce the prevalence of chronic Pseudomonas
      aeruginosa respiratory infection, previously thought to be inevitable in most
      children with CF. These included neonatal screening (1975), regular
      microbiological monitoring (1975), early antibiotic treatment of first isolations
      of P. aeruginosa (1985), intensive intravenous antibiotic treatment where
      nebulized antibiotics failed to eradicate P. aeruginosa (1988), and separate
      clinics for patients chronically infected with P. aeruginosa and uninfected
      patients (1991). The aim of this study was to assess the impact of these
      interventions. All 232 patients receiving full-time care at the Leeds Paediatric
      CF Centre during the period January 1990-December 2000 were categorized into four
      groups: never grown P. aeruginosa; free of P. aeruginosa for at least 1 year;
      intermittent grower of P. aeruginosa with </=50% of months with samples positive
      for P. aeruginosa over the previous 12 months; and chronic P. aeruginosa
      infection with >50% of months with samples positive for P. aeruginosa over the
      previous 12 months. The yearly prevalence of patients having chronic P.
      aeruginosa infection fell significantly during the study, from 24.5% in 1990 to
      18.1% in 2000 (P < 0.05), despite an increase in mean age of patients from 7.73
      to 9.42 years. The number of patients aged less than 11 years who had chronic P.
      aeruginosa infection fell from 23.8% in January 1990 to only 4.3% by December
      2000. The annual incidence and mean age of first acquisition of P. aeruginosa did
      not alter significantly. In conclusion, antipseudomonal management strategies
      were associated with both reduced prevalence, and an increase in the mean age of
      onset of chronic P. aeruginosa infection.

PMID- 14730655
TI  - Effects of inhaled fluticasone propionate in children less than 2 years old with
      recurrent wheezing.
AB  - Our objective was to evaluate the efficacy and safety of two doses of fluticasone
      propionate (FP) in young children with recurrent wheezing and risk factors for
      asthma. Our study design was a randomized, double-blind, placebo-controlled
      comparison of inhaled FP 50 mcg twice daily (FP 100) and 125 mcg twice daily (FP
      250), for 6 months. Outcome measures included number of wheezing episodes, days
      on albuterol, height standard deviation score (height SDS), osteocalcin (OC),
      bone alkaline phosphatase fraction (AKP), insulin-like growth factor-binding
      protein 3 (IGFBP-3), and serum levels of cortisol (SC). Our subjects were 30
      patients, aged 7-24 months. Mean wheezing episodes were 6.0 +/- 1.9, 1.9 +/- 1.9,
      and 2.8 +/- 1.2; mean days of albuterol use were 24.3 +/- 1.3, 6.5 +/- 0.8, and
      9.1 +/- 0.8, per patient for placebo, FP100, and FP250 groups, respectively.
      There was a significant reduction in clinical outcome in the two FP groups
      compared to placebo (P < 0.01). No significant correlations were found between FP
      dosage and height SDS, OC, AKP, IGFBP-3, and SC. In conclusion, in young children
      with asthmatic symptoms, FP at 50 and 125 mcg b.i.d. for 6 months significantly
      improved respiratory symptoms without causing significant side effects on growth
      and bone metabolism.

PMID- 14730656
TI  - Effect of high-dose fluticasone propionate on bone density and metabolism in
      children with asthma.
AB  - Significant concern remains over the long-term side effects of inhaled steroids.
      This cross-sectional study evaluates the effect of high-dose inhaled fluticasone
      propionate (FP) on biochemical markers of bone metabolism and bone density in
      children with asthma. Children with chronic asthma using FP >/= 1,000 mcg daily
      for at least 6 months, and healthy controls, were entered in the study. No
      children had taken oral prednisolone within the previous month. Fasting morning
      serum was analyzed for bone formation markers, and spot urine for bone resorption
      markers. Dual-energy X-ray absorptiometry (DEXA) results were reviewed in a
      subgroup of patients. Forty-nine children with asthma and 32 controls were
      recruited. The mean FP dose was 771.2 +/- 253.35 mcg/m2/day. Unpaired t-test
      analysis revealed no significant difference in biochemical markers studied. In
      subjects with asthma; 13 of 37 (35.1%) had lumbar spine density more than one
      standard deviation below the mean (P = 0.001). This fell to 6/37 (16.2%) with
      bone age correction (NS). In conclusion, no significant reduction in bone
      metabolism or bone age-corrected bone mineral density was observed in children
      with asthma on prolonged high doses of inhaled FP.

PMID- 14730657
TI  - Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid
      treatment in children with asthma.
AB  - This double-blind, placebo-controlled, randomized, parallel-group, multicenter
      study was conducted in 302 children aged 6-11 years with asthma not optimally
      treated with inhaled corticosteroids alone. Patients continued with their
      existing dose of inhaled corticosteroids and in addition received placebo,
      formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered
      via Turbuhaler). Terbutaline was available as reliever medication. The primary
      efficacy variable was change from baseline in morning peak expiratory flow (PEF);
      secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)),
      serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of
      life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning
      PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF
      and FEV(1) were also significantly increased compared with placebo, with no
      statistically significant difference between formoterol doses. Lung-function
      improvements compared with placebo were greater in the middle of the day. Twelve
      hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39
      l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in
      the formoterol 4.5-microg group. The incidence of severe exacerbations in both
      formoterol groups was numerically lower than in the placebo group, indicating
      that formoterol may have the potential to improve exacerbation control in
      children. Both formoterol doses were well-tolerated, and tolerance to the drug's
      bronchodilator effect was not observed. Formoterol provided sustained
      improvements in lung function and was well-tolerated in children with asthma
      suboptimally treated with inhaled corticosteroids alone.

PMID- 14730658
TI  - Insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) expression in
      human lung in RDS and BPD.
AB  - We hypothesize that IGF-1 and IGF-1R proteins are upregulated in lung epithelia
      and fibroblasts in RDS compared to normal development, and are further
      upregulated in BPD. We used immunohistochemistry to evaluate IGF-1 and IGF-R
      expression in lungs from autopsies of human stillbirths and RDS and BPD patients.
      IGF-1 and IGF-R immunostaining were present in fetal, RDS, and BPD lungs. In RDS,
      IGF-1 was present in alveolar epithelium and prominent in columnar and cuboidal
      airway epithelia. In BPD lungs, immunostaining was intensely increased in both
      airway and alveolar epithelia and in mesenchyme. The immunostaining index in
      bronchial epithelial cells and peribronchial myofibroblasts was significantly
      higher in BPD compared to RDS. IGF-1R expression was minimal in fetal lung and
      found mainly in mesenchyme. IGF-1R was increased in mesenchyme in RDS. In BPD it
      was especially increased in peribronchial and perialveolar mesenchyme.
      Immunostaining index for IGF-1R in epithelial cells and peribronchial
      myofibroblasts was increased in BPD compared to RDS. IGF-1 and IGF-R expression
      is low during fetal development, but is acutely upregulated in RDS, and persists
      with further upregulation in BPD.

PMID- 14730659
TI  - CC chemokine concentrations increase in respiratory distress syndrome and
      correlate with development of bronchopulmonary dysplasia.
AB  - Inflammation is one of the primary processes underlying respiratory distress
      syndrome (RDS) and its evolution into bronchopulmonary dysplasia (BPD).
      Recruitment and subsequent activation of macrophages in the lung are mediated by
      CC chemokines. The role of CC chemokines has not been extensively studied in the
      course of RDS. Serial tracheal aspirates (TA) were obtained from 56 mechanically
      ventilated infants with birth weights less than 1,500 g during intervals in the
      first 21 days of life. Tracheal aspirate concentrations of monocyte
      chemoattractant proteins-1,2,3 (MCP-1,2,3) and macrophage inflammatory proteins
      1alpha and -1beta (MIP-1alpha, MIP-1beta) were determined by enzyme-linked
      immunosorbent assay (ELISA). Tracheal aspirate concentrations of MCP-1, MCP-2,
      MCP-3, and MIP-1beta increased during the first week of life in infants with RDS,
      whereas MIP-1alpha concentrations did not increase appreciably. Increased TA
      cytokine concentrations were associated with the development of BPD. Maximal TA
      concentrations of MCP-1, MCP-2, MCP-3, MIP-1alpha, and MIP-1beta were
      significantly higher in infants who were oxygen-dependent at 28 postnatal days
      compared to infant who were not. Similarly, maximal TA MCP-1, MCP-2, and MCP-3
      but not MIP-1alpha and MIP-1beta concentrations were significantly higher in
      infants who were oxygen-dependent at 36 weeks of postconceptional age (PCA) than
      those who were not oxygen-dependent at 36 weeks PCA. Histologic chorioamnionitis
      and isolation of Ureaplasma urealyticum from the airways were associated with
      higher maximal TA concentrations of MIP-1alpha and MIP-1beta. Pulmonary
      hemorrhage was associated with increased maximal concentrations of MCP-1, MCP-2,
      and MCP-3. These data suggest a role for CC chemokines in the development of BPD
      in the newborn infant.

PMID- 14730660
TI  - Harvesting airway surface liquid: a comparison of two techniques.
AB  - The quantity and composition of airway surface liquid (ASL) are essential to host
      defense. To date, attempts to harvest ASL and measure its composition have
      yielded conflicting results. We investigated the physical principles underlying
      two techniques that were proposed for harvesting ASL: filter paper pledgets and
      polyethylene catheters. We compared the force and pressure generation and the
      kinematics of capillarity-induced fluid uptake with both techniques. Both have
      significant limitations for harvesting ASL, generating physiologically
      significant pressures (filter paper, 60.4 Pa; polyethylene, 14.3 Pa) that could
      potentially compromise epithelial integrity. Furthermore, filter paper generates
      a force 85-fold higher than the polyethylene catheter, which is associated with a
      very high rate of uptake of liquid and a large total amount of liquid relative to
      ASL thickness. While the PE catheter harvests liquid more gently, it is only
      effective when ASL surface tension is below 31 mN/m. These limitations likely
      account for some of the variability in reported ASL composition, and highlight
      the need for improved methods for harvesting ASL.

PMID- 14730661
TI  - BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of
      E. coli DH5alpha in vitro.
AB  - Gram-negative bacterial lung infections and chronic bacterial colonization are
      major threats for pediatric cystic fibrosis (CF) patients. Besides impeded
      mucociliary clearance, other mechanisms that contribute to increased
      susceptibility to infections are presumed. The bactericidal/permeability
      increasing protein (BPI), which is delivered by neutrophil granulocytes and
      mucosal epithelial cells, is one of the most potent innate antibiotics against
      Gram-negative bacteria and endotoxin. Antineutrophil cytoplasmic autoantibodies
      against BPI (BPI-ANCA) have been found in up to 90% of CF patients, and titers
      correlated inversely with lung function parameters. As major pulmonary damage is
      mediated by Gram-negative bacteria and their products, the question was raised as
      to whether BPI-ANCA can inhibit the antibiotic function of BPI in these patients.
      Sera of 23 pediatric CF patients were analyzed for the presence of BPI-ANCA by
      indirect immunofluorescence, ELISA, epitope mapping, and Western blotting.
      Patients' IgG were tested in a bacterial growth inhibition assay with recombinant
      BPI (rBPI) and an amino-terminal fragment of BPI (rBPI(21)) that retains
      antibiotic activity for inhibition of the antibiotic function of BPI against E.
      coli DH5alpha in vitro. BPI was recognized by 21 of 23 patients' sera in our
      detection assays. Thirteen of 23 patients' BPI-ANCA (56%) could inhibit the
      antibiotic function in vitro. Moreover, epitope mapping over the whole BPI
      sequence revealed that more patients' BPI-ANCA recognize the amino-terminal part
      of BPI than can be detected by ELISA. Thus, in pediatric CF patients, BPI-ANCA
      may contribute to diminished bacterial clearance by inhibiting the antibiotic
      function of BPI.

PMID- 14730662
TI  - Differences between adolescents' and parents' reports of health-related quality
      of life in cystic fibrosis.
AB  - Our objective was to determine the magnitude and direction of differences between
      adolescents with cystic fibrosis (CF) and their parents' reports of the
      adolescents' health-related quality of life (HRQOL) as measured by the adolescent
      and parent versions of the Child Health Questionnaire (CHQ). Sixty-two
      adolescents (mean age, 13.7 years; 46% female; mean forced expired volume in 1
      sec, 73%) completed the 87-item adolescent form, and their parents (79% mothers;
      77% working full or part time) completed the 50-item parent form of the CHQ
      during a routine clinic visit. For each scale, ANOVA was used to determine
      pairwise differences between adolescent and parent scale scores. For scales in
      which a significant parent-adolescent difference existed, ANCOVA was used to
      determine disease and demographic factors independently associated with
      differences in scores. Finally, responses for each pair were compared only on
      similarly worded items within each scale. For the full CHQ scales, adolescents
      rated their HRQOL significantly better than did their parents with regard to
      General Health (mean difference, 12.4 points), Role Function/Physical (mean
      difference, 9.0 points), Behavior (mean difference, 4.8 points), and Physical
      Function (mean difference, 4.0 points). No demographic or health factor was
      associated consistently with differences in parent-adolescent scores. When only
      similarly worded items were compared, adolescents still tended to rate their
      HRQOL better, but the difference was significant only for General Health (P =
      0.0005), where adolescents rated themselves less susceptible to illness and less
      worried about their health than their parents. In conclusion, optimal measurement
      of adolescent HRQOL will likely require determining both parent and adolescent
      perceptions of HRQOL.

PMID- 14730663
TI  - Redesigned face mask improves "real life" aerosol delivery for Nebuchamber.
AB  - The currently available facemask interface for the Nebuchamber (N) valved-holding
      chamber (VHC) provides a very poor seal to the face, which, on average, decreases
      the aerosol dose and was previously shown to increase the variability of aerosol
      delivery. The efficiency of a redesigned mask (RD) for the Nebuchamber with a
      potentially better seal was compared to the standard mask (SM) supplied with the
      N in a randomized real-life crossover clinical trial. Twenty children (mean age,
      26 +/- 10 months) were randomized to use the Nebuchamber for 1 week with the old
      mask and then for another week with the newer mask, and vice versa. Filters,
      changed daily, inserted between the mask and the VHC, trapped the delivered drug
      (budesonide). The dose of budesonide was quantified by high-performance liquid
      chromatography (HPLC). Use of the redesigned mask improved aerosol delivery to
      the filter by 30%, compared to the SM (mean 28.1 +/- 7.7% of nominal dose with RD
      vs. 21.6 +/- 9.6% with SM, P = 0.017). The relatively high within-subject
      variability in aerosol delivery (36-38%) did not change, however. Facemasks are
      arguably the most important determinants of aerosol delivery. The newly developed
      RD for the Nebuchamber proved to be considerably more efficient than the SM for
      aerosol delivery to young children. Patient-related factors may be more important
      with respect to the variability observed.

PMID- 14730664
TI  - Pulmonary involvement in tuberous sclerosis.
AB  - Tuberous sclerosis is a neurocutaneous syndrome involving many tissues. Pulmonary
      involvement is rare. Pulmonary cases are usually women of child-bearing age who
      present with spontaneous pneumothorax or progressive dyspnea. In childhood and,
      even more, in male patients, pulmonary involvement by tuberous sclerosis is
      exceptional. We report on a 4-year-old male patient diagnosed in the first months
      of life with tuberous sclerosis with predominantly respiratory symptoms
      (frequently with acute RDS criteria), in whom lung involvement was pathologically
      confirmed.

PMID- 14730665
TI  - Nodular pulmonary vasculitis in a twelve-year-old boy.
AB  - A 12-year-old boy presented with left shoulder pain during physical exercise and
      complained of uncommon sweating and fatigue. Diagnostic evaluation revealed a
      solitary pulmonary nodule in the left upper lobe. All laboratory values were
      within normal limits, except for an elevated level of antineutrophil cytoplasmic
      antibodies directed against myeloperoxidase (p-ANCA). Surgery was performed, and
      pathological examination showed a localized granulomatous vasculitis.
      Antineutrophil cytoplasmic antibodies directed against affinity purified
      proteinase 3 (p-ANCA) concentrations returned to baseline within 6 months, and
      the patient has done well during a follow-up period of 2 years. While nodular
      vasculitis is known to occur in Wegener's granulomatosis, to the best of our
      knowledge, this case represents the first c-ANCA negative primary pulmonary
      vasculitis in childhood.

PMID- 14730666
TI  - Differentiation between peptides containing acetylated or tri-methylated lysines
      by mass spectrometry: an application for determining lysine 9 acetylation and
      methylation of histone H3.
AB  - Histone acetylation and methylation play a critical role in transcription and
      gene regulation. Identification of sites of lysine acetylation and methylation in
      histones or other proteins by mass spectrometry (MS) is of increasing interest.
      In this paper, we report the use of MS to differentiate between peptides
      containing acetylated or tri-methylated lysines. High accuracy matrix-assisted
      laser desorption/ionization-time of flight MS gives better than five parts per
      million measurement accuracy, which is sufficient to verify acetylation and/or
      methylation. Electrospray ionization tandem mass spectrometry was used to assign
      modification sites and to differentiate acetylation from methylation. Typically,
      an immonium ion at m/z 98 corresponds to a mono-methylated lysine and an immonium
      ion at m/z 126 corresponds to an acetylated lysine. The neutral loss ion (MH(+)
      59) is unique for a tri-methylated lysine. For a peptide with two or more
      modification sites of acetylation or tri-methylation or one site containing
      partial acetylation and tri-methylation, the a(2)-, b(2)-type ion is the
      characteristic index for an acetylated lysine whereas the b(2)-59 ion is
      indicative of a tri-methylated lysine in the N-terminus. The y-type ions and y-59
      ions are characteristic of an acetylated lysine and a tri-methylated lysine at
      the C-terminus, respectively. We demonstrated that a lysine in a peptide modified
      by methylation or acetylation can be differentiated by MS using our method. Even
      if more then one lysine is present in a peptide and different modifications of
      this amino acid occur, they can be distinguished. This method was successful for
      the determination of the acetylation and methylation status of lysine 9 of
      histone H3 in chicken erythrocytes and human HeLa cell lines.

PMID- 14730667
TI  - C-terminal sequencing method for peptides and proteins by the reaction with a
      vapor of perfluoric acid in acetic anhydride.
AB  - A successive C-terminal amino acid truncation reaction of peptides and proteins
      with a vapor generated from a low-concentrated perfluoric acid in acetic
      anhydride is presented. The reaction products were analyzed with matrix-assisted
      laser desorption/ionization-time of flight mass-spectrometry giving molecular
      mass ions of the C-terminal truncated peptides or proteins from which the C
      terminal sequence information can be deduced. Acetylation reaction preceded the
      truncation reaction in order to protect the amino groups and other reactive
      groups in peptides and proteins, and after the truncation reaction, hydration
      reaction was carried out to afford cleaner mass spectra.

PMID- 14730668
TI  - Immunostaining with dissociable antibody microarrays.
AB  - The availability of a large number of biological materials such as cDNA,
      antibodies, recombinant proteins, and tissues has promoted the development of
      microarray technologies that make use of these materials in high-throughput
      screening assays. However, because microarray technologies have been less
      successful in examining proteins than DNA and mRNA, there is a need for improved
      protein microarray systems. To address this need, we developed an antibody
      microarray-based immunostaining method that can analyze the properties of a large
      number of proteins simultaneously. In this method, antibodies are arrayed and
      immobilized on a solid support and cells bearing antigens of interest are
      attached to a second support. Apposition of the two supports allows the
      antibodies to dissociate from the array support and bind to the cellular
      antigens. After separation of the supports, antigen-bound antibodies can be
      detected by standard secondary antibody techniques. These "dissociable" antibody
      arrays were used to detect both the expression and subcellular localization of a
      large number of specific proteins in various cultured cell types.

PMID- 14730669
TI  - Optimization of the first dimension for separation by two-dimensional gel
      electrophoresis of basic proteins from human brain tissue.
AB  - A major cause of poor resolution in the alkaline pH range of two-dimensional
      electrophoresis (2-DE) gels is unsatisfactory separation of basic proteins in the
      first dimension. We have compared methods for the separation of basic proteins in
      the isoelectric focusing dimension of human brain proteins. The combined use of
      anodic cup-loading and the hydroxyethyldisulphide containing solution (DeStreak)
      produced better resolution in both analytical and micropreparative protein loaded
      2-DE gels than the other methods investigated.

PMID- 14730670
TI  - A detergent- and cyanogen bromide-free method for integral membrane proteomics:
      application to Halobacterium purple membranes and the human epidermal membrane
      proteome.
AB  - A simple and rapid method for characterizing hydrophobic integral membrane
      proteins and its utility for membrane proteomics using microcapillary liquid
      chromatography coupled on-line with tandem mass spectrometry (microLC-MS/MS) is
      described. The present technique does not rely on the use of detergents, strong
      organic acids or cyanogen bromide-mediated proteolysis. A buffered solution of
      60% methanol was used to extract, solubilize, and tryptically digest proteins
      within a preparation of Halobacterium (H.) halobium purple membranes. Analysis of
      the digested purple membrane proteins by microLC-MS/MS resulted in the
      identification of all the predicted tryptic peptides of bacteriorhodopsin,
      including those that are known to be post-translationally modified. In addition,
      40 proteins from the purple membrane preparation were also identified, of which
      80% are predicted to contain between 1 and 16 transmembrane domains. To evaluate
      the general applicability of the method, the same extraction, solubilization, and
      digestion conditions were applied to a plasma membrane fraction prepared from
      human epidermal sheets. A total of 117 proteins was identified in a single
      microLC-MS/MS analysis, of which 55% are known to be integral or associated with
      the plasma membrane. Due to its simplicity, efficiency, and absence of MS
      interfering compounds, this technique can be used for the characterization of
      other integral membrane proteins and may be concomitantly applied for the
      analysis of membrane protein complexes or large-scale proteomic studies of
      different membrane samples.

PMID- 14730671
TI  - Comparing expression level-dependent features in codon usage with protein
      abundance: an analysis of 'predictive proteomics'.
AB  - Synonymous codon usage is a commonly used means for estimating gene expression
      levels of Escherichia coli genes and has also been used for predicting highly
      expressed genes for a number of prokaryotic genomes. By comparison of expression
      level-dependent features in codon usage with protein abundance data from two
      proteome studies of exponentially growing E. coli and Bacillus subtilis cells, we
      try to evaluate whether the implicit assumption of this approach can be confirmed
      with experimental data. Log-odds ratio scores are used to model differences in
      codon usage between highly expressed genes and genomic average. Using these, the
      strength and significance of expression level-dependent features in codon usage
      were determined for the genes of the Escherichia coli, Bacillus subtilis and
      Haemophilus influenzae genomes. The comparison of codon usage features with
      protein abundance data confirmed a relationship between these to be present,
      although exceptions to this, possibly related to functional context, were found.
      For species with expression level-dependent features in their codon usage, the
      applied methodology could be used to improve in silico simulations of the outcome
      of two-dimensional gel electrophoretic experiments.

PMID- 14730672
TI  - Proteogenomic mapping as a complementary method to perform genome annotation.
AB  - The accelerated rate of genomic sequencing has led to an abundance of completely
      sequenced genomes. Annotation of the open reading frames (ORFs) (i.e., gene
      prediction) in these genomes is an important task and is most often performed
      computationally based on features in the nucleic acid sequence. Using recent
      advances in proteomics, we set out to predict the set of ORFs for an organism
      based principally on expressed protein-based evidence. Using a novel search
      strategy, we mapped peptides detected in a whole-cell lysate of Mycoplasma
      pneumoniae onto a genomic scaffold and extended these "hits" into ORFs bound by
      traditional genetic signals to generate a "proteogenomic map". We were able to
      generate an ORF model for M. pneumoniae strain FH using proteomic data with a
      high correlation to models based on sequence features. Ultimately, we detected
      over 81% of the genomically predicted ORFs in M. pneumoniae strain M129 (the
      originally sequenced strain). We were also able to detect several new ORFs not
      originally predicted by genomic methods, various N-terminal extensions, and some
      evidence that would suggest that certain predicted ORFs are bogus. Some of these
      differences may be a result of the strain analyzed but demonstrate the robustness
      of protein analysis across closely related genomes. This technique is a cost
      effective means to add value to genome annotation, and a prerequisite for
      proteome quantitation and in vivo interaction measures.

PMID- 14730673
TI  - Process for the integrated extraction, identification and quantification of
      metabolites, proteins and RNA to reveal their co-regulation in biochemical
      networks.
AB  - A novel extraction protocol is described with which metabolites, proteins and RNA
      are sequentially extracted from the same sample, thereby providing a convenient
      procedure for the analysis of replicates as well as exploiting the inherent
      biological variation of independent samples for multivariate data analysis. A
      detection of 652 metabolites, 297 proteins and clear RNA bands in a single
      Arabidopsis thaliana leaf sample was validated by analysis with gas
      chromatography coupled to a time of flight mass spectrometer for metabolites, two
      dimensional liquid chromatography coupled to mass spectrometry for proteins, and
      Northern blot analysis for RNA. A subset of the most abundant proteins and
      metabolites from replicate analysis of different Arabidopsis accessions was
      merged to form an integrative dataset allowing both classification of different
      genotypes and the unbiased analysis of the hierarchical organization of proteins
      and metabolites within a real biochemical network.

PMID- 14730674
TI  - Proteome characterization of human T helper 1 and 2 cells.
AB  - T helper (Th) cells can be polarized into two different main subtypes, Th1 and
      Th2 cells. Their activation is linked to the eradication of different pathogens
      and to dissimilar immunological dysfunctions, which implies differences also in
      their protein expression patterns. To identify these differences, CD4(+) T cells
      were isolated from human cord blood, polarized in vitro to Th1 and Th2 and
      activated via CD3 and CD28. Cells were lysed, soluble proteins were separated
      with two-dimensional electrophoresis and differing protein spots were identified
      with peptide mass fingerprinting. The expression of 14 proteins differed in Th1
      and Th2 cells after both 7 and 14 days of polarization. Twelve of the proteins
      could be identified, most of which are new in this context. Two proteins were
      differentially modified in the two cell types. Especially, N-terminal acetylation
      of cyclophilin A was stronger in Th1 than in Th2 cells. To compare the RNA and
      the protein levels of the identified genes, mRNA expression was measured with
      Affymetrix oligonucleotide microarrays (HG-U133A). The mRNA and protein
      expression level correlated only in six cases out of eleven, which highlights the
      complementary roles that proteomics and transcriptomics have in the elucidation
      of biological phenomena.

PMID- 14730675
TI  - Proteomic analysis of nuclear proteins from proliferative and differentiated
      human colonic intestinal epithelial cells.
AB  - Self-renewing tissues such as the intestine contain progenitor proliferating
      cells which subsequently differentiate. Cell proliferation and differentiation
      involve gene regulation processes which take place in the nucleus. A human
      intestinal epithelial cell line model (Caco2/TC7) which reproduces these dynamic
      processes has been used to perform proteomic studies on nuclear proteins. Nuclei
      from Caco2/TC7 cells at proliferative and differentiated stages were purified by
      subcellular fractionation. After two-dimensional gel electrophoresis separation
      and ruthenium staining, 400 protein spots were detected by image analysis. Eighty
      five spots corresponding to 60 different proteins were identified by matrix
      assisted laser desorption/ionization mass spectrometry in nuclei from
      proliferative cells. Comparison of nuclear proteomes from proliferative or
      differentiated cells by differential display resulted in the identification of
      differentially expressed proteins such as nucleolin, hnRNP A2/B1 and hnRNP A1. By
      using Western blot analysis, we found that the expression and number of specific
      isoforms of these nuclear proteins decreased in differentiated cells.
      Immunocytochemistry experiments also showed that in proliferative cells nucleolin
      was distributed in nucleoli-like bodies. In contrast, hnRNPs A2/B1 and A1 were
      dispersed throughout the nucleus. This study of the nuclear proteome from
      intestinal epithelial cells represents the first step towards the establishment
      of a protein database which will be a valuable resource in future studies on the
      differential expression of nuclear proteins in response to physiological,
      pharmacological and pathological modulations.

PMID- 14730676
TI  - Environmental stress responses in Lactobacillus: a review.
AB  - Environmental stress responses in Lactobacillus, which have been investigated
      mainly by proteomics approaches, are reviewed. The physiological and molecular
      mechanisms of responses to heat, cold, acid, osmotic, oxygen, high pressure and
      starvation stresses are described. Specific examples of the repercussions of
      these effects in food processing are given. Molecular mechanisms of stress
      responses in lactobacilli and other bacteria are compared.

PMID- 14730677
TI  - Global changes in gene expression observed at the transition from growth to
      stationary phase in Listeria monocytogenes ScottA batch culture.
AB  - Listeria monocytogenes is a food-borne Gram-positive bacterium that is
      responsible for a variety of infections (worldwide) annually. The organism is
      able to survive a variety of environmental conditions and stresses, however, the
      mechanisms by which L. monocytogenes adapts to environmental change are yet to be
      fully elucidated. An understanding of the mechanism(s) by which L. monocytogenes
      survives unfavourable environmental conditions will aid in developing new food
      processing methods to control the organism in foodstuffs. We have utilized a
      proteomic approach to investigate the response of L. monocytogenes batch cultures
      to the transition from exponential to stationary growth phase. Proteomic analysis
      showed that batch cultures of L. monocytogenes perceived stress and began
      preparations for stationary phase much earlier (approximately A(600) = 0.75, mid
      exponential) than predicted by growth characteristics alone. Global analysis of
      the proteome revealed that the expression levels of more than 50% of all proteins
      observed changed significantly over a 7-9 h period during this transition phase.
      We have highlighted ten proteins in particular whose expression levels appear to
      be important in the early onset of the stationary phase. The significance of
      these findings in terms of functionality and the mechanistic picture are
      discussed.

PMID- 14730678
TI  - An analysis of the proteomic profile for Thermoanaerobacter tengcongensis under
      optimal culture conditions.
AB  - The genome of Thermoanaerobacter tengcongensis is estimated to encode 2588
      theoretical proteins. In this study, we have vitalized approximately 46% of the
      theoretical proteome experimentally using a proteomic strategy that combines
      three different methods, shotgun digestion plus high-performance liquid
      chromatography (HPLC) with ion-trap tandem mass spectrometry (shotgun-liquid
      chromatography (LC)/MS), one-dimensional sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) plus HPLC with ion-trap tandem mass spectrometry
      (one-dimensional electrophoresis (1DE)-LC/MS), and two-dimensional gel
      electrophoresis plus matrix-assisted laser desorption/ionization-time of flight
      mass spectrometry (2DE-MALDI-TOF-MS). Of the 1200 proteins identified, as few as
      76 proteins were globally found by all three approaches, and notably, most of
      these proteins were in the soluble fraction. However, there were a number of
      unique proteins detected by one method only, suggesting that our strategy
      provides a means toward obtaining a comprehensive view of protein expression
      profile. Proteins from the major metabolic pathways are strongly represented on
      the map, and a number of these enzymes were identified by more than one proteomic
      method. Based upon the proteins identified in the present study, we are able to
      broaden the understanding of how T. tengcongensis survives under high temperature
      environment, whereas several of its properties can not be fully explained by
      genome data.

PMID- 14730679
TI  - Global analysis of the Ralstonia metallidurans proteome: prelude for the large
      scale study of heavy metal response.
AB  - A proteome map of Ralstonia metallidurans strain CH34 was constructed using two
      dimensional (2-D) gel electrophoresis in combination with automated Edman
      degradation and mass spectrometry (MS). R. metallidurans CH34 is the type-strain
      of a family of highly related strains characterized by their multiple resistance
      to millimolar amounts of heavy metals, conferred by two large plasmids. The
      protein content of this bacterium grown in minimal medium was separated by 2-D
      gel electrophoresis using various pH gradients. Protein identification was
      carried out via N-terminal amino acid sequencing, matrix assisted laser
      desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) and tandem
      MS. So far, 224 different proteins were characterized from 352 protein spots.
      Although the proteome map is still not complete, one could appraise the
      importance of proteomics for genome analyses through (i). the identification of
      previously undetected open reading frames, (ii). the identification of proteins
      not encoded by the already sequenced genome fragments, (iii). the
      characterization of protein-encoding genes spanning two different contigs,
      enabling their merging, and (iv). the precise delineation of the N-terminus of
      several proteins. Finally, this map will prove a useful tool in the
      identification of proteins differentially expressed in the presence of different
      heavy metals.

PMID- 14730680
TI  - Use of two-dimensional gel electrophoresis proteome reference maps of
      dinoflagellates for species recognition of causative agents of harmful algal
      blooms.
AB  - The sample preparation procedures established for Prorocentrum triestinum were
      adapted to cover both thecate and athecate dinoflagellates. Further, whether
      trichloroacetic acid (TCA) precipitation can be used to fix and preserve the
      harmful or nuisance species from local waters that they infest was tested.
      Optimized technical procedures developed were used to generate proteome reference
      maps for eight other local causative species of harmful algal blooms (HABs):
      Prorocentrum micans, Prorocentrum minimum, Prorocentrum sigmoides, Prorocentrum
      dentatum, Scrippsiella trochoidea, Karenia longicanalis, Karenia digitata and
      Karenia mikimotoi; together with one American species Karenia brevis (Florida,
      USA). These proteome maps were used to test their ability for species recognition
      in a mixed culture of dinoflagellates and whether such investigations will
      provide a comparative view at a global level. Comparisons of proteome profiles
      were made (i). between closely related species within the same family; (ii).
      between distantly related species belonging to different types, i.e.,
      gymnodinioids, prorocentroids or peridinioids, or (iii). between different
      groups, i.e., thecate (armored) dinoflagellate cells against athecate (naked or
      unarmored) dinoflagellate cells. Species-specific two-dimensional electrophoresis
      (2-DE) protein profiles were observed in all ten species and it was possible to
      distinguish between even closely related species within the same family. To
      demonstrate the extent of reproducibility and usefulness of these 2-DE reference
      maps, 2-DE has been used to analyze three geographically distinct isolates of
      Prorocentrum dentatum, and to distinguish species composition in a mixed culture.
      Application of 2-D PAGE analysis to differentiate between taxonomically confused
      strains of a single species could be a powerful taxonomic tool.

PMID- 14730681
TI  - Proteomics as a tool to improve investigation of substantial equivalence in
      genetically modified organisms: the case of a virus-resistant tomato.
AB  - At present, the so-called "substantial equivalence" is the only widely accepted
      criterion for deciding whether or not a transgenic food is, from an alimentary
      point of view, to be considered totally correspondent to the "traditional" one
      from which it derives. Although never exactly defined, it deals with a comparison
      between the chemical composition of the two foods. A more in-depth analysis can
      be performed by one of the most suitable methods that allows for the simultaneous
      screening of many components without prior identification, the analysis of the
      proteome. As a model for testing this kind of approach, we compared protein
      expression of two types of tomato plants, having the same genetic background,
      except for a virus resistance trait introduced by genetic engineering. When
      proteins extracted from seedlings of the two types were analyzed by two
      dimensional electrophoresis, no significant differences, either qualitative or
      quantitative, were detected, indicating that in this case the expression of major
      proteins was unmodified by the genetic manipulation. Fifteen proteins were
      identified by peptide mass fingerprinting.

PMID- 14730682
TI  - Grape berry biochemistry revisited upon proteomic analysis of the mesocarp.
AB  - Major soluble proteins of grapevine ripe berries were extracted from six
      different cultivars including non vinifera, with trichloroacetic acid acetone and
      resolved in two-dimensional electrophoresis (2-DE) gels. About three hundred
      spots were detected on the 2-DE map after colloidal blue staining. From 2-DE map
      of cv. Gamay mesocarp, 67 proteins were identified (p > 0.95) using matrix
      assisted laser desorption/ionization-mass spectrometry analysis. About 34%, 19%,
      and 13% of identified proteins play, respectively, a role in energy metabolism,
      defense, and stress response and primary metabolism. 2-DE analysis revealed
      considerable accumulation of dehydrin, invertase, and a putative transcription
      factor in the ripe fruit, in addition to pathogenesis-related proteins such as
      chitinase and thaumatin-like proteins previously documented as prevalent proteins
      in ripe berries. Actual translation of redundant transcripts of unclear function
      such as Grip31, Grip32, and Grip61 recently cloned in ripe grape berries was
      confirmed. The relative abundance of UDP-glucose pyrophosphorylase and vacuolar
      invertase strongly supported a key role of the apoplastic pathway of sugar
      loading during ripening. Comparative analysis shows that differences between
      cultivars were low, but different isoforms of alcohol dehydrogenase and of a
      transcription factor of hexose transporter were obvious in the six cultivars.
      Peptide mass fingerprinting suggests that the Adh isoforms would be Adh2/Adh6 or
      Adh2/Adh7 dimers and unambiguously shows that considerable deletion/insertion
      inside Adh7 are not cloning artifacts.

PMID- 14730683
TI  - Proteome analysis of cultivar-specific deregulations of Oryza sativa indica and
      O. sativa japonica cellular suspensions undergoing rice yellow mottle virus
      infection.
AB  - We have used two-dimensional gel electrophoresis with mass spectrometry analysis
      to study the temporal patterns of protein expression during RYMV (Rice yellow
      mottle virus) infection in rice cells of two cultivars: IR64, Oryza sativa
      indica, susceptible, and Azucena, O. sativa japonica, partially resistant to
      RYMV. Proteomic analysis of nonstressed and RYMV inoculated cells showed
      statistically significant changes in the relative levels of 40 IR64 proteins and
      24 Azucena proteins. Protein identification using mass spectrometry was attempted
      for all the differentially regulated proteins. This global analysis detected 32
      hypothetical "new" proteins. Nineteen differentially regulated proteins were
      identified for IR64 cultivar, while 13 were identified for Azucena cultivar,
      including proteins in three functional categories: metabolism, stress-related
      proteins, and translation. These data revealed that a number of proteins
      regulated by abiotic stress response pathway were activated by RYMV in both
      cultivars (such as salt-induced protein, heat shock proteins (HSPs), superoxide
      dismutase (SOD), and others have functions consistent with the susceptibility or
      partially resistance trait (such as dehydrin, proteins involved in glycolysis
      pathway).

PMID- 14730684
TI  - In vivo uniform (15)N-isotope labelling of plants: using the greenhouse for
      structural proteomics.
AB  - Isotope labelling of proteins is important for progress in the field of
      structural proteomics. It enables the utilisation of the power of nuclear
      magnetic resonance spectroscopy (NMR) for the characterisation of the three
      dimensional structures and corresponding dynamical features of proteins. The
      usual approach to obtain isotopically labelled protein molecules is by expressing
      the corresponding gene in bacterial or yeast host organisms, which grow on
      isotope-enriched media. This method has several drawbacks. Here, we demonstrate
      that it is possible to fully label a plant with (15)N-isotopes. The advantage of
      in vivo labelling of higher organisms is that all constituting proteins are
      labelled and become available as functional, post-translationally modified,
      correctly folded proteins. A hydroponics set-up was used to create the first
      example of a uniformly (15)N-labelled (> 98%) plant species, the potato plant
      (Solanum tuberosum L., cv. Elkana). Two plants were grown at low costs using
      potassium-[(15)N]-nitrate as the sole nitrogen source. At harvest time, a total
      of 3.6 kg of potato tubers and 1.6 kg of foliage, stolons and roots were
      collected, all of which were fully (15)N-labelled. Gram quantities of soluble
      (15)N-labelled proteins (composed mainly of the glycoprotein patatin and Kunitz
      type protease inhibitors) were isolated from the tubers. NMR results on the
      complete proteome of potato sap and on an isolated protease inhibitor illustrate
      the success of the labelling procedure. The presented method of isotope labelling
      is easily modified to label other plants. Its envisioned impact in the field of
      structural proteomics of plants is discussed.

PMID- 14730685
TI  - Proteome comparative analysis of gynogenetic haploid and diploid embryos of
      goldfish (Carassius auratus).
AB  - Recently, it was found that in the gynogenetic haploid and diploid embryos of
      goldfish, which have exactly the same genome, the haploid condition results in
      obstruction of gene expression and abnormal development while the diploid embryos
      have normal gene expression and development. A diploid-dependent regulatory
      apparatus was proposed to regulate gene expression. To study the difference at
      the protein expression level of the embryos of haploid and diploid in
      development, we extracted the total proteins of both the gynogenetic haploid and
      diploid embryos of goldfish in the same eye formation stage. Two-dimensional
      polyacrylamide gel electrophoresis was used to separate proteins. The stained gel
      images were analyzed with the PDQUEST software. A part of protein spots that were
      differentially expressed in haploid and diploid embryos were identified by matrix
      assisted laser desorption/ionisation-time of flight-mass spectrometry and
      database analysis. Sixteen protein spots that were absolutely different (only
      expressed in diploid embryos but not in haploid embryos or vice versa) and 16
      protein spots that were up- and downregulated were identified unambiguously,
      which include some proteins that are correlative with eyes development, nerve
      development, developing regulation, cell differentiation, and signal
      transduction. The different significantly gene expression during embryos
      developing between diploid and haploid is demonstrated.

PMID- 14730687
TI  - Nonreducing two-dimensional gel electrophoresis for the detection of Bence Jones
      proteins in serum and urine.
AB  - Nonreducing two-dimensional gel electrophoresis (2-DE) is described for the study
      of immunoglobulin disorders with asynchronous production of single chains. Unlike
      classical reducing 2-DE, this method can distinguish between complex intact
      molecules and their free single chains (with different degrees of polymerization)
      and will thus be helpful for diagnosis of this type of disease. Examples are
      taken from canine patients, but the method may also be applied to both urine and
      serum specimens from other species. Nonreducing 2-DE thus represents a useful
      tool complementary to classical 2-DE, when further information about the
      appearance of free subunits or modifications of proteins are required, even in
      the presence of intact molecules.

PMID- 14730686
TI  - Mining biomarkers in human sera using proteomic tools.
AB  - One of the major difficulties in mining low abundance biomarkers from serum or
      plasma is due to the fact that a small number of proteins such as albumin, alpha2
      macroglobulin, transferrin, and immunoglobulins, may represent as much as 80% of
      the total serum protein. The large quantity of these proteins makes it difficult
      to identify low abundance proteins in serum using traditional 2-dimensional
      electrophoresis. We recently used a combination of multidimensional liquid
      chromatography and gel electrophoresis coupled to matrix-assisted laser
      desorption/ionization-quadrupole-time of flight and Ion Trap liquid
      chromatography-tandem mass spectrometry to identify protein markers in sera of
      Alzheimer's disease (AD), insulin resistance/type-2 diabetes (IR/D2), and
      congestive heart failure (CHF) patients. We identified 8 proteins that exhibit
      higher levels in control sera and 36 proteins that exhibit higher levels in
      disease sera. For example, haptoglobin and hemoglobin are elevated in sera of AD,
      IR/D2, and CHF patients. The levels of several other proteins including
      fibrinogen and its fragments, alpha 2-macroglobulin, transthyretin, pro-platelet
      basic protein, protease inhibitors clade A and C, as well as proteins involved in
      the classical complement pathway such as complement C3, C4, and C1 inhibitor,
      were found to differ between IR/D2 and control sera. The sera levels of proteins,
      such as the 10 kDa subunit of vitronectin, alpha 1-acid glycoprotein,
      apolipoprotein B100, fragment of factor H, and histidine-rich glycoprotein were
      observed to be different between AD and controls. The differences observed in
      these biomarker candidates were confirmed by Western blot and the enzyme-linked
      immunosorbent assay. The biological meaning of the proteomic changes in the
      disease states and the potential use of these changes as diagnostic tools or for
      therapeutic intervention will be discussed.

PMID- 14730688
TI  - Comparison of gene expression between left atria and left ventricles from non
      diseased humans.
AB  - We examine the reliability and accuracy of gene array technology in analyzing
      differences in gene expression between human non-diseased left atrium and left
      ventricle. We have used cDNA gene arrays and validated those data by carefully
      designed quantitative real-time polymerase chain reaction (PCR). We have
      identified pitfalls using cDNA gene array technology based on comparisons with
      other gene array studies and with changes reported for the levels of expression
      of the genes corresponding to these cDNAs. The high error rate reported here
      underscores the cautionary comments reported by others in this field.

PMID- 14730689
TI  - Identification of tumor-associated proteins in oral tongue squamous cell
      carcinoma by proteomics.
AB  - Oral tongue carcinoma is an aggressive tumor that particularly affects chronic
      smokers, drinkers and betel squid chewers. Patients often present symptoms at a
      late stage, and there is a high recurrence rate after treatment. In this article,
      we report the first proteomic analysis of oral tongue carcinoma to globally
      search for tumor related proteins. Apart from helping us to understand the
      molecular pathogenesis of the carcinoma, these proteins may also have potential
      clinical applications as biomarkers, enabling the tumor to be identified at an
      early stage in high risk individuals, treatment response to be predicted, and
      residual or recurrent carcinoma to be detected sooner after treatment. The
      protein expression profiles of ten oral tongue squamous cell carcinomas and their
      matched normal mucosal resection margins were examined by two-dimensional gel
      electrophoresis and matrix-assisted laser desorption/ionization-time of flight
      mass spectroscopy. A number of tumor-associated proteins including heat shock
      protein (HSP)60, HSP27, alpha B-crystalline, ATP synthase beta, calgranulin B,
      myosin, tropomyosin and galectin 1 were consistently found to be significantly
      altered in their expression levels in tongue carcinoma tissues, compared with
      their paired normal mucosae. The expression profile portrays a global protein
      alteration that appears specific to oral tongue cancer. The potential of
      utilizing these tumor related proteins for screening cancer and monitoring
      recurrence warrants further investigation.

PMID- 14730695
TI  - Downregulation of steroidogenic acute regulatory protein (StAR) gene expression
      by cyclic AMP in cultured Schwann cells.
AB  - Steroidogenic acute regulatory protein (StAR) plays a key role in the
      availability of cholesterol to the inner mitochondrial membrane, where the first
      step of steroidogenesis, its conversion to pregnenolone, takes place. Here, we
      demonstrate for the first time that the StAR gene is also expressed in the rat
      sciatic nerve and in cultured Schwann cells. The addition to the culture medium
      of the cAMP-elevating agent forskolin or of the cAMP analogue 8Br-cAMP produced a
      time-course extinction of StAR gene expression. An inverse relationship was
      demonstrated between StAR gene expression and the intracellular cAMP content.
      Accordingly, pharmacological inhibition of the activities of Schwann cell
      adenylyl cyclase or of phosphodiesterase IV resulted in modifications of StAR
      gene expression. Since StAR gene expression is stimulated by cAMP in classical
      steroidogenic cells, our work is the first demonstration of a negative regulation
      of StAR gene by cAMP.

PMID- 14730696
TI  - Na,K-ATPase alpha 2 inhibition alters calcium responses in optic nerve
      astrocytes.
AB  - Experiments were conducted to test the effect of 1 microM ouabain, an Na,K-ATPase
      inhibitor, on capacitative calcium entry (CCE) and calcium responses elicited by
      ATP in rat optic nerve astrocytes. In the rat, 1 microM ouabain is sufficient to
      inhibit the alpha2 Na,K-ATPase, but not the alpha1. Immortalized astrocytes
      derived from Na,K-ATPase alpha2 homozygous knockout (KO) mice and wild-type (WT)
      littermates were also used. Cytosolic calcium and sodium concentrations were
      measured using Fura-2 and SBFI, respectively. The magnitude of the increase in
      cytosolic calcium concentration during CCE was significantly greater in rat
      astrocytes exposed to 1 microM ouabain. To measure calcium release from stores,
      cells were exposed to ATP in the absence of extracellular calcium. In astrocytes
      exposed to 1 microM ouabain, a significantly greater calcium response to ATP was
      observed. 1 microM ouabain was shown to inhibit ATP hydrolysis in membrane
      material containing Na,K-ATPase alpha2 and alpha1 isoforms (rat muscle) but not
      in membranes containing only Na,K-ATPase alpha1 (rat kidney). In intact
      astrocytes, 1 microM ouabain did not alter the cell-wide cytosolic sodium
      concentration. In mouse Na,K-ATPase alpha2 KO astrocytes, the calcium increase
      during CCE was significantly higher than in WT cells, as was the magnitude of the
      calcium response to ATP. In KO astrocytes, but not WT, the cytosolic calcium
      increase during CCE was insensitive to 1 microM ouabain. Taken together, the
      results suggest that selective inhibition of the Na,K-ATPase alpha2 isoform has
      the potential to change calcium signaling and CCE.

PMID- 14730697
TI  - Heregulin and forskolin-induced cyclin D3 expression in Schwann cells: role of a
      CCAAT promoter element and CCAAT enhancer binding protein.
AB  - Heregulin, a polypeptide growth factor, and forskolin, an adenylyl cyclase
      activator, synergistically stimulate expression of cyclin D3 and cell division in
      Schwann cells. Heregulin induces expression in Schwann cells of a luciferase
      reporter gene linked to the cyclin D3 promoter. Forskolin markedly augments
      reporter expression in the presence of heregulin. Deletion analysis identified
      several promoter sites that contribute to high-level reporter expression in
      heregulin- and forskolin-treated Schwann cells. A promoter fragment that contains
      103 bp of 5'-flanking sequence produced significant reporter expression in
      heregulin- and forskolin-stimulated cells. Deletion of a consensus CCAAT site
      within this promoter fragment caused a nearly complete loss of reporter
      expression. Similar results were obtained when CCAAT site mutations were
      introduced into the promoter. Heregulin and forskolin increased steady-state
      levels of CCAAT/enhancer binding protein-beta (C/EBPbeta) in Schwann cells.
      Mobility shift assays identified proteins in Schwann cell nuclear extracts that
      formed stable complexes with the cyclin D3 CCAAT promoter element and were
      disrupted by anti-C/EBPbeta antibody. Transfection of Schwann cells with
      C/EBPbeta cDNA increased cyclin D3 reporter expression. In contrast to these
      results, mutation of a cAMP response element in the cyclin D3 promoter had only a
      modest effect on heregulin- and forskolin-stimulated reporter expression. These
      findings demonstrate that C/EBPbeta plays a key role in the heregulin and cAMP
      dependent regulation of cyclin D3 expression in Schwann cells.

PMID- 14730698
TI  - Cell size-proliferation relationship in rat glioma cells.
AB  - The homeostasis of the central nervous system is highly controlled by glial cells
      and is dramatically altered in the case of glioma. In this respect, the complex
      connection between cell size and division is of particular importance and needs
      clarifying. In order to investigate this connection, cell number and volume were
      measured in C6 rat glioma cells under different experimental conditions,
      including continuous cell culture, Cl- channel blockade, and anisotonicity, and
      in the presence of an inhibitory conditioned medium collected from cell cultures
      or in a medium containing a low level of fetal calf serum. The rate of cell
      proliferation changed with cell volume in a bell-shaped manner, so that it is
      optimal within a cell volume window and appears to be controlled by low and high
      cell size checkpoints. The cell size-proliferation relationship can be defined by
      Boltzmann-like equations, which may reflect the effects of macromolecular
      crowding on proteins controlling the cell cycle progression. Altogether, these
      observations indicate that glioma cell proliferation is controlled predominantly
      but not exclusively by cell size-dependent mechanisms.

PMID- 14730699
TI  - Glial activation modulates glutamate neurotoxicity in cerebellar granule cell
      cultures.
AB  - We studied the influence of glial cells on the neuronal response to glutamate
      toxicity in cerebellar granule cell cultures. We compared the effect of glutamate
      on neuronal viability in neuronal vs. neuronal-glial cultures and determined this
      effect after pretreating the cultures with the lipopolysaccharide (LPS) of
      Escherichia coli, agent widely used to induce glial activation. Morphological
      changes in glial cells and nitric oxide (NO) production were evaluated as
      indicators of glial activation. We observed that glutamate neurotoxicity in
      neuronal-glial cultures was attenuated in a certain range of glutamate
      concentration when compared to neuronal cultures, but it was enhanced at higher
      glutamate concentrations. This enhanced neurotoxicity was associated with
      morphological changes in astrocytes and microglial cells in the absence of NO
      production. LPS treatment induced morphological changes in glial cells in
      neuronal-glial cultures as well as NO production. These effects occurred in the
      absence of significant neuronal death. However, when LPS-pretreated cultures were
      treated with glutamate, the sensitivity of neuronal-glial cultures to glutamate
      neurotoxicity was increased. This was accompanied by additional morphological
      changes in glial cells in the absence of a further increase in NO production.
      These results suggest that quiescent glial cells protect neuronal cells from
      glutamate neurotoxicity, but reactive glial cells increase glutamate
      neurotoxicity. Therefore, glial cells play a key role in the neuronal response to
      a negative stimulus, suggesting that this response can be modified through an
      action on glial cells.

PMID- 14730700
TI  - Sulfatide is a negative regulator of oligodendrocyte differentiation: development
      in sulfatide-null mice.
AB  - Galactosylceramide (GalC) and its sulfated analogue, sulfatide, are major
      galactosphingolipid components of myelin and oligodendrocyte plasma membranes in
      the nervous system. We previously hypothesized that these galactolipids play
      functional roles in the regulation of oligodendrocyte terminal differentiation by
      acting as sensors/transmitters of environmental information. Evidence strongly
      supports this idea. First, these molecules are initially expressed on the cell
      surface at the interface at which oligodendrocyte progenitors first enter
      terminal differentiation. Second, exposure of oligodendrocyte progenitors to anti
      GalC/-sulfatide (RmAb) or antisulfatide (O4), but not anti-GalC (O1), antibodies
      leads to the reversible arrest of oligodendrocyte lineage progression at this
      interface. Third, in cerebroside galactosyl transferase-null mice (Cgt(-/-)) that
      are unable to synthesize either GalC or sulfatide, terminal differentiation and
      morphological maturation of oligodendrocytes are enhanced. In the present study,
      we examined oligodendrocytes differentiation in cerebroside sulfotransferase-null
      mice (Cst(-/-)) that lack sulfatide but express GalC. We show that cerebroside
      sulfotransferase mRNA expression begins already in the embryonic spinal cord and
      progressively increases with age, that the late progenitor marker POA is not
      synthesized in the absence of this enzyme, and that, most notably, there is a two
      to threefold enhancement in the number of terminally differentiated
      oligodendrocytes both in culture and in vivo, similar to that in mice lacking
      both GalC and sulfatide. We conclude that primarily sulfatide, rather than GalC,
      is a key molecule for the negative regulation of oligodendrocyte terminal
      differentiation.

PMID- 14730701
TI  - Remyelination of cytokine- or antibody-demyelinated CNS aggregate cultures is
      inhibited by macrophage supplementation.
AB  - Remyelination in CNS aggregate cultures is determined both by macrophage
      enrichment and the mode of demyelination. Despite the same degree of myelin loss,
      accumulation of MBP in anti-MOG antibody-demyelinated aggregates overtakes that
      of controls, while recovery is significantly delayed following IFN-gamma-induced
      demyelination. In antibody-treated cultures, remyelination was associated with a
      significant increase in culture supernatant levels of TGF-beta1, FGF-2, and PDGF
      AA as well as an induction of TNF-alpha immediately following removal of the
      demyelinating insult. The impaired recovery in IFN-gamma-treated cultures,
      denoted by a significant reduction in TGF-beta1, was reversed by treatment with
      hrTGF-beta1. Macrophage supplementation of the cultures prior to the addition of
      either demyelinating agent induced a greater degree of myelin loss followed by
      incomplete remyelination in both cases. This failure to remyelinate was
      associated in both groups with a several-fold elevation in TNF-alpha and with
      modest increases in PDGF-AA and FGF-2 in the antibody-treated cultures. In
      contrast, macrophage supplementation to mature cultures in the absence of any
      demyelinating treatment resulted in enhanced accumulation of MBP associated with
      a promyelinative growth factor and TNF-alpha profile similar to that in
      aggregates enriched with macrophages at the outset of the culture period. Hence,
      effector elements of the adaptive immune response appear to override
      promyelinogenic in favor of proinflammatory macrophage factors in mature CNS
      aggregates, counteracting the potential for myelin repair.

PMID- 14730702
TI  - Induction of chemokines in human astrocytes by picornavirus infection requires
      activation of both AP-1 and NF-kappa B.
AB  - Infection with different picornaviruses can cause meningitis/encephalitis in
      humans and experimental animals. To investigate the mechanisms of such
      inflammatory diseases, potential chemokine gene activation in human astrocytes
      was investigated following infection with Theiler's murine encephalomyelitis
      virus (TMEV), coxsackievirus B3 (CVB3), or coxsackievirus B4 (CVB4). We report
      that all these viruses are potent inducers for the expression of interleukin-8
      (IL-8) and monocyte chemoattractant protein-1 (MCP-1) genes in primary human
      astrocytes, as well as in an established astrocyte cell line (U-373MG). Further
      studies indicated that both activator protein-1 (AP-1) and NF-kappaB
      transcription factors are required in the activation of chemokine genes in human
      astrocytes infected with various picornaviruses. Interestingly, the pattern of
      activated chemokine genes in human astrocytes is quite restricted compared to
      that in mouse astrocytes infected with the same viruses, suggesting species
      differences in gene activation. This may result in potential differences in the
      pathogenic outcome in each species.

PMID- 14730703
TI  - CD44-independent hepatocyte growth factor/c-Met autocrine loop promotes malignant
      peripheral nerve sheath tumor cell invasion in vitro.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are invasive peripheral nerve
      neoplasms that express both the receptor tyrosine kinase c-Met and its ligand
      hepatocyte growth factor (HGF). The combined expression of these proteins has
      been implicated in tumor cell growth and metastasis. However, HGF/c-Met autocrine
      activity requires the presence of a serine protease, the HGF activator (HGFA),
      and, in some cells, the CD44 transmembrane glycoprotein. Here, we found that
      HGFA, HGF, c-Met, and CD44 are coexpressed in MPNSTs but their localization did
      not correlate with increased cell proliferation. The ST8814 MPNST cell line also
      expresses all of these proteins, can convert pro-HGF to active HGF, and exhibits
      constitutive c-Met phosphorylation. Blocking c-Met activity or expression
      inhibits the invasive behavior of these cells but not their proliferation.
      Interestingly, although a CD44 splice variant contributes to MPNST cell invasion
      and interacts with c-Met and HGF in ST8814 cells, it is not required for c-Met
      activation. These data indicate that an HGF/c-Met autocrine loop can promote
      MPNST invasion through a CD44-independent mechanism and suggest that c-Met, HGFA,
      and HGF are potential molecular targets to inhibit MPNST metastasis.

PMID- 14730704
TI  - CNS axons retain their competence for myelination throughout life.
AB  - An important question relevant to developing remyelination therapies is whether
      axons that remain without myelin sheaths after an episode of demyelination retain
      myelination competence. To resolve this, we have developed a model of
      transplantation into the nerve fibre layer of the adult rat retina, where the
      axons are unmyelinated. In the adult, these axons can be myelinated by
      transplantation of both the oligodendrocyte progenitor cells (OPCs) and an OPC
      line (CG4). The extent of myelination achieved following transplantation of OPCs
      is the same in young adult recipients (2 months old) as that which occurs in old
      adult recipients (12-18 months old), indicating that there are no changes in
      axons remaining unmyelinated for many months that would prevent effective
      remyelination. This finding suggests that chronically demyelinated regions of
      axons such as those in seen in multiple sclerosis are likely to remain competent
      to be remyelinated.

PMID- 14730705
TI  - Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing
      cells from human nose.
AB  - Several studies have demonstrated the potential of olfactory ensheathing cells
      for the repair of central and peripheral nerve injury. However, the majority of
      these studies have been performed with olfactory ensheathing cells derived from
      the olfactory bulbs, situated inside the skull. A more clinically relevant source
      of olfactory ensheathing cells is the olfactory mucosa, located in the nose. To
      be successful, an autologous transplant of nasal ensheathing glia would require a
      large number of purified cells. To address this issue, we have focused our
      research on three neurotrophic factors, namely nerve growth factor (NGF), brain
      derived neurotrophic factor (BDNF), and neurotrophin 3 (NT3). We show here that
      their respective receptors, TrkA, TrkB, TrkC, as well as p75(NTR) (the low
      affinity NGF receptor), are expressed in vitro by the nasal ensheathing cells;
      the three neurotrophins promote purification and proliferation of these glial
      cells, with an optimal concentration of 50 ng/ml; and human ensheathing cells can
      be easily biopsied and highly purified using a serum-free medium supplemented
      with NT3. This technique opens the door for clinical trials in which nasal
      ensheathing cells will be autotransplanted in humans suffering from nerve injury.

PMID- 14730706
TI  - Association of the ecto-ATPase NTPDase2 with glial cells of the peripheral
      nervous system.
AB  - Cellular signaling via extracellular nucleotides appears to play a major role in
      the functioning of the peripheral nervous system. Information regarding the
      functional characterization of nucleotide P2 receptors or their expression
      pattern has been accumulating rapidly; however, very little is known regarding
      the distribution of ecto-nucleotidases in the periphery. The extracellular level
      of nucleotides is controlled by ecto-nucleotidases, whereby the three membrane
      bound members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase)
      family are of special functional importance. Using enzyme histochemistry and
      immunostaining, we demonstrate that NTPDase2 is associated with nonmyelinating
      Schwann cells of the rat sciatic nerve, whereas NTPDase1 is restricted to blood
      vessel walls. NTPDase2 immunoreactivity was detected from embryonic day E18
      onward, suggesting that immature Schwann cells express the enzyme. With the onset
      of myelination, NTPDase2 immunoreactivity remained associated solely with
      nonmyelinating Schwann cells. NTPDase2 was absent from perisynaptic Schwann cells
      but was associated with fibroblasts covering the endplate at some distance. In
      addition, NTPDase2 immunoreactivity was associated with the satellite glial cells
      in dorsal root ganglia and sympathetic ganglia, and with the enteric glia
      surrounding the cell bodies of ganglionic neurons of the myenteric and the
      submucous plexus. In contrast to NTPDase1, NTPDase2 preferentially hydrolyzes
      nucleoside triphosphates over nucleoside diphosphates and thus can act either in
      inactivating or in producing P2 receptor ligands. Our results suggest that
      NTPDase2 plays an important role in the control of nucleotide-mediated activation
      of peripheral neurons or glia and in the dialogue between these two cell types.

PMID- 14730707
TI  - Glutamate transporter expression and function in human glial progenitors.
AB  - Glutamate is the major neurotransmitter of the brain, whose extracellular levels
      are tightly controlled by glutamate transporters. Five glutamate transporters in
      the human brain (EAAT1-5) are present on both astroglia and neurons. We
      characterize the profile of three different human astroglial progenitors in
      vitro: human glial restricted precursors (HGRP), human astrocyte precursors
      (HAPC), and early-differentiated astrocytes. EAAT 1, EAAT3, and EAAT4 are all
      expressed in GRPs with a subsequent upregulation of EAAT1 following
      differentiation of GRPs into GRP-derived astrocytes in the presence of bone
      morphogenic protein (BMP-4). This corresponds to a significant increase in the
      glutamate transport capacity of these cells. EAAT2, the transporter responsible
      for the bulk of glutamate transport in the adult brain, is not expressed as a
      full-length protein, nor does it appear to have functional significance (as
      determined by the EAAT2 inhibitor dihydrokainate) in these precursors. A splice
      variant of EAAT2, termed EAAT2b, does appear to be present in low levels,
      however. EAAT3 and EAAT4 expression is reduced as glial maturation progresses
      both in astrocyte precursors and early-differentiated astrocytes and is
      consistent with their role in adult tissues as primarily neuronal glutamate
      transporters. These human glial precursors offer several advantages as tools for
      understanding glial biology because they can be passaged extensively in the
      presence of mitogens, afford the potential to study the temporal changes in
      glutamate transporter expression in a tightly controlled fashion, and are
      cultured in the absence of neuronal coculture, allowing for the independent study
      of astroglial biology.

PMID- 14730708
TI  - Antibodies against astrocyte M1 and M2 muscarinic cholinoceptor from
      schizophrenic patients' sera.
AB  - We demonstrated the presence of circulating antibodies from schizophrenic
      patients able to interact with cultured astrocytes activating muscarinic
      acetylcholine receptors (mAChRs). Sera and purified IgG from 15 paranoid
      schizophrenic and 15 age-matched normal subjects were studied by indirect
      immunofluorescence (IFI), flow cytometry, dot blot, enzyme immunoassay (ELISA),
      and radioligand competition assays. Astrocyte membranes and/or a synthetic
      peptide, with identical amino acid sequence of human M(1) and M(2) mAChR, were
      used as antigens. By IFI and flow cytometry procedures, we proved that serum
      purified IgG fraction from schizophrenic patients, reacted to astrocyte cell
      surface. The same antibodies were able to inhibit the binding of the specific
      mAChR radioligand (3)H-QNB. Using synthetic peptide for dot blot and ELISA, we
      demonstrated that these antibodies reacted against the second extracellular loop
      of human cerebral M(1) and M(2) mAChR. Also, the corresponding affinity-purified
      antipeptide antibody displayed an agonistic-like activity associated to specific
      M(1) and M(2) mAChR activation, increasing inositol phosphates accumulation and
      decreasing cyclic AMP production, respectively. This article gives support to the
      participation of an autoimmune process in schizophrenia disease.

PMID- 14730709
TI  - Cloning, transport properties, and differential localization of two splice
      variants of GLT-1 in the rat CNS: implications for CNS glutamate homeostasis.
AB  - At least two splice variants of GLT-1 are expressed by rat brain astrocytes,
      albeit in different membrane domains. There is at present only limited data
      available as to the spatial relationship of such variants relative to the
      location of synapses and their functional properties. We have characterized the
      transport properties of GLT-1v in a heterologous expression system and conclude
      that its transport properties are similar to those of the originally described
      form of GLT-1, namely GLT-1alpha. We demonstrate that GLT-1alpha is localized to
      glial processes, some of which are interposed between multiple synapse types,
      including GABAergic synapses, whereas GLT-1v is expressed by astrocytic
      processes, at sites not interposed between synapses. Both splice variants can be
      expressed by a single astrocyte, but such expression is not uniform over the
      surface of the astrocytes. Neither splice variant of GLT-1 is evident in brain
      neurons, but both are abundantly expressed in some retinal neurons. We conclude
      that GLT-1v may not be involved in shaping the kinetics of synaptic signaling in
      the brain, but may be critical in preventing spillover of glutamate between
      adjacent synapses, thereby regulating intersynaptic glutamatergic and GABAergic
      transmission. Furthermore, GLT-1v may be crucial in ensuring that low levels of
      glutamate are maintained at extrasynaptic locations, especially in pathological
      conditions such as ischemia, motor neurone disease, and epilepsy.

PMID- 14730711
TI  - Microglial tau undergoes phosphorylation-independent modification after ischemia.
AB  - Tau2 is a phosphorylation-independent antibody that immunolabels neurofibrillary
      tangles (NFTs) of Alzheimer type and microglia around ischemic foci on formalin
      fixed, paraffin-embedded sections. We found that copresence of polyethyleneglycol
      p-isooctylphenyl ether (Triton X-100; TX) with tau2 abolished its
      immunoreactivity (IR) in these microglia but not its IR on NFTs. Tau2
      immunoreactive bands, exclusively retrieved in Tris-soluble fraction of brain
      homogenates from ischemic foci, normal human and bovine brains, were of similar
      electrophoretic mobility, indicating that tau2 IR in these microglia is unrelated
      to hyperphosphorylation of tau. These tau2-immunoreactive bands except those from
      bovine brain were abolished in the copresence of TX. This was not due to washing
      out of tau, because similar immunoreactive bands were detectable with another
      antitau antibody even under a higher concentration of TX and because washing
      after TX exposure restored similar tau2 IR both on immunohistochemistry and
      immunoblot. These findings are explained if tau, modified after ischemia,
      undergoes a reversible conformational change on TX exposure. Because conformation
      at Ser101 of bovine tau is crucial for its affinity to tau2, this Ser-like
      conformation mimicked by its human counterpart Pro may represent pathological
      modification of tau shared by microglia around ischemic foci and NFTs. Relative
      resistance of tau2 epitope in NFTs to TX exposure suggests that tau woven into
      NFTs confers additional stability to this pathological modification on tau2
      epitope. Susceptibility of tau2 epitope to TX, seen in these microglia, is shared
      with glial cytoplasmic inclusions and will show its conformational state to be
      different from that in NFTs.

PMID- 14730710
TI  - Activated glia induce neuron death via MAP kinase signaling pathways involving
      JNK and p38.
AB  - Chronic glial activation in neurodegenerative diseases contributes to neuronal
      dysfunction and neuron loss through production of neuroinflammatory molecules.
      However, the molecular mechanisms, particularly the signal transduction pathways
      involved in glia-dependent neuron death, are poorly understood. As a first step
      to address this question, we used a neuron-glia co-culture system that allows
      diffusion of soluble molecules between glia and neurons to test the potential
      importance of mitogen-activated protein kinase (MAPK) signaling pathways in the
      glia-induced neuron death. Activation of glia in co-culture by lipopolysaccharide
      (LPS) induced apoptotic-like neuron death. The MAPKs tested (p38, JNK, ERK1/2)
      were activated in both glia and neurons following LPS treatment, suggesting their
      involvement in both glial activation and neuronal response to diffusible, glia
      derived neurotoxic molecules. Inhibitors of p38 and JNK partially blocked neuron
      death in the LPS-treated co-culture, whereas an ERK1/2 pathway inhibitor did not
      protect neurons. These results show that p38 and JNK MAPKs, but not ERK1/2 MAPK,
      are important signal transduction pathways contributing to glia-induced neuron
      death.

PMID- 14730712
TI  - Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of
      microglia.
AB  - Microglia, the resident macrophage of the brain, mediates immune and inflammatory
      responses in the central nervous system (CNS). Activation of microglia and
      secretion of inflammatory cytokines associate with the pathogenesis of CNS
      diseases, including multiple sclerosis (MS), Alzheimer's disease (AD),
      Parkinson's disease, prion disease, and AIDS dementia. Microbial pathogens,
      cytokines, chemokines, and costimulatory molecules are potent inducers of
      microglial activation in the CNS. Signaling through its receptor, IL-3 induces
      the activation of JAK-STAT and MAP kinase pathways in microglial cells. In this
      study, we found that in vitro treatment of EOC-20 microglial cells with
      tyrphostin AG490 blocked IL-3-induced tyrosine phosphorylation of JAK2, STAT5A,
      and STAT5B signaling proteins. Stable transfection of EOC-20 cells with a
      dominant negative JAK2 mutant also blocked IL-3-induced tyrosine phosphorylation
      of JAK2, STAT5A, and STAT5B in microglia. The blockade of JAK2-STAT5 pathway
      resulted in a decrease in IL-3-induced proliferation and expression of CD40 and
      major histocompatibility complex class II molecules in microglia. These findings
      highlight the fact that JAK2-STAT5 signaling pathway plays a critical role in
      mediating IL-3-induced activation of microglia.

PMID- 14730713
TI  - Localization of neuregulin isoforms and erbB receptors in myelinating glial
      cells.
AB  - Neuregulins (NRGs) are growth factors present in neurons and glial cells of the
      central and peripheral nervous systems and play a role in the survival,
      proliferation, and differentiation of these cells. We now report the localization
      of the two major isoforms of NRG (alpha and beta) and their receptors (erbB) in
      cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups.
      Immunocytochemistry and Western blots for NRG and erbB receptors in defined
      subcellular fractions were utilized to assess cellular localization. Less
      differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but
      not the processes, while only NRG-1beta was found in the nucleus. In contrast,
      more differentiated oligodendrocytes contained neither isoform in the nucleus
      while both isoforms were colocalized in the cytoplasm and cell processes. In
      Schwann cells, both NRG-1beta and NRG-1alpha were colocalized in the cytoplasm
      and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG-1
      isoforms, although NRG-1beta was predominant. ErbB2 and erbB3 receptors, which
      transduce the NRG-1 signal in Schwann cells, were found throughout the cytoplasm
      and in the processes and were also localized in the cell nucleus. The nuclear
      localization of NRG-1 isoforms and/or erbB receptors in both cell types was
      confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of
      Schwann cells with mitotic agents increased NRG-1beta expression in the nucleus
      and dramatically suppressed NRG-1alpha expression throughout the cell. The
      functional implications of this differential localization in myelinating cells
      are discussed.

PMID- 14730714
TI  - Dystrophic microglia in the aging human brain.
AB  - We have studied microglial morphology in the human cerebral cortex of two
      nondemented subjects using high-resolution LN-3 immunohistochemistry. Several
      abnormalities in microglial cytoplasmic structure, including deramification,
      spheroid formation, gnarling, and fragmentation of processes, were identified.
      These changes were determined to be different from the morphological changes that
      occur during microglial activation and they were designated collectively as
      microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia
      revealed that these were much more prevalent in the older subject (68-year-old)
      than in the younger one (38-year-old). Thus, we conclude that microglial
      dystrophy is a sign of microglial cell senescence. We hypothesize that microglial
      senescence could be important for understanding age-related declines in cognitive
      function.

PMID- 14730715
TI  - [Preparation of natto and its function in health care].

PMID- 14730717
TI  - [Risk factors for plantar fasciitis].

PMID- 14730716
TI  - [Research on Tibetan drugs: current status and prospects].

PMID- 14730718
TI  - [18-year-old patient with breathing-related chest pain. Idiopathic, recurrent
      pericarditis].

PMID- 14730719
TI  - [Advances in the study on transdermal permeation of active elements of natural
      drugs in vitro].

PMID- 14730720
TI  - Multidisciplinary collaboration is helpful to physiotherapy research.

PMID- 14730721
TI  - Living with chronic renal failure: patients' experiences of their physical and
      functional capacity.
AB  - BACKGROUND AND PURPOSE: Several studies have shown that patients with chronic
      renal failure have reduced physical exercise capacity compared with the expected
      norm. There are, however, few qualitative studies showing ways in which patients
      experience their condition in terms of physical and functional capacity, and the
      limitations this imposes on their daily lives. The aim of the present study was
      to describe and analyse ways in which patients with chronic renal failure, in the
      pre-dialysis phase and patients undergoing haemodialysis or peritoneal dialysis,
      experienced their physical and functional capacity in their daily lives. METHOD:
      Semi-structured interviews were used to collect data, which were then analysed
      according to a contextual analysis within a phenomenographic approach. RESULTS:
      Analysis yielded a system of categories describing patients' experiences of
      mental and physical fatigue, physical and functional capacity, in terms of effect
      on performance and endurance, and their experience of temporal stress, in terms
      of lack of time as well as lack of peace in their daily lives. CONCLUSIONS: The
      results of the study will contribute to our understanding of how these patients
      experience their daily lives, and will help when meeting patients with chronic
      renal failure. This knowledge enables physiotherapists to focus rehabilitation
      training on problem areas that are important to patients themselves.

PMID- 14730722
TI  - Concurrent validity of the Berg Balance Scale and the Dynamic Gait Index in
      people with vestibular dysfunction.
AB  - BACKGROUND AND PURPOSE: The Berg Balance Scale is a reliable and valid measure
      that is used to assess characteristics of balance. The Dynamic Gait Index is a
      relatively new measure that has been used to record dynamic gait tasks in people
      with vestibular dysfunction. The purpose of the present study was to determine
      the concurrent validity of the Dynamic Gait Index with the Berg Balance Scale in
      people with vestibular disorders. METHOD: A retrospective review of the charts of
      people who met the criteria of having completed both the Berg Balance Scale and
      the Dynamic Gait Index during their first physiotherapy visit. Seventy patients
      (19 male, 51 female) were identified through the retrospective review of the
      charts of people referred for vestibular rehabilitation with varying diagnoses of
      vestibular and balance dysfunction. All were seen at a tertiary medical centre in
      an outpatient physiotherapy setting. Their age range was from 14 to 88 years
      (mean 65 years). RESULTS: Correlation between the scores on the Dynamic Gait
      Index and the Berg Balance Scale was moderate but significant by use of the
      Spearman rank order correlation (r = 0.71; p < 01). No difference was found
      between scores on the Dynamic Gait Index or Berg Balance Scale based on gender or
      diagnosis. A significant difference was identified on the Berg Balance Scale
      between older and younger people with vestibular disorders. Using previously
      established criteria to determine increased risk of falling, the Berg Balance
      Scale and the Dynamic Gait Index agreed 63% of the time. CONCLUSIONS: The
      moderate correlation between the Dynamic Gait Index and the Berg Balance Scale
      establishes the concurrent validity of the Dynamic Gait Index in people with
      vestibular dysfunction. Both these measures provide valuable information to
      clinicians about patients' functional balance capabilities. However, the lack of
      perfect correlation indicates that the tests measure different aspects of
      balance. The Dynamic Gait Index appears to be a more sensitive assessment tool in
      identifying people with vestibular disorders who are at increased risk for
      falling, based on currently published criteria.

PMID- 14730723
TI  - Forceplate and accelerometer measures for evaluating the effect of muscle fatigue
      on postural control during one-legged stance.
AB  - BACKGROUND AND PURPOSE: The control of balance is vital in many sporting
      activities as well as in activities of daily life. In order to treat deficiencies
      properly valid and reliable methods are needed to evaluate different aspects of
      stability. Muscle fatigue has been proposed to cause a change in postural control
      strategy, and the use of different tools and variables might therefore elucidate
      these changes. The aims of the present study were: to investigate if forceplate
      and accelerometer measurements about postural control during one-legged stance
      indicate changes in postural control strategy after fatiguing exercise; and to
      investigate the correlation between forceplate and accelerometer measurements
      obtained before and after fatiguing exercise. METHOD: The study used an
      experimental design. Twenty-three healthy women (mean age 26.8 years; range 20-34
      years) were studied. Forceplate and accelerometer data were obtained
      simultaneously and consisted of measures of centre of pressure movements and
      horizontal trunk acceleration in medio-lateral and antero-posterior directions.
      The calf muscles of the right leg were fatigued by repeated heel rises. RESULTS:
      The average amplitude of centre of pressure movements and trunk acceleration
      increased, whereas the average velocity of centre of pressure movements decreased
      during fatigue. These changes indicate a change of movement strategy. Moderate
      correlation between trunk acceleration and centre of pressure movements was seen,
      confirming the link between the variables, but indicating that different aspects
      of the ability to control balance were measured. CONCLUSIONS: Calf muscle fatigue
      has a short-lasting effect on body balance, with measurements indicating a change
      in postural control strategy. Different tools and variables are needed to
      identify different balance control strategies. The procedures used in the present
      study may be modified to identify subjects with inadequate capacity to choose
      between balance control strategies; they are also applicable in clinical settings
      outside a laboratory environment.

PMID- 14730724
TI  - Physiotherapy intervention in two people with HIV or AIDS-related peripheral
      neuropathy.

PMID- 14730725
TI  - The podiatron: an adjunct to physiotherapy treatment for Guillain-Barre syndrome?

PMID- 14730726
TI  - Proprioceptive deficit after ankle injuries.

PMID- 14730727
TI  - [40th anniversary of the activities of the Institute of Biomedical Problems].

PMID- 14730728
TI  - [Cryptobiosphere of Mars].
AB  - The US Viking missions (1975-1976) failed to discover any biological activity on
      the surface of Mars. Yet, life may exist in the planet lithosphere which was
      found to contain a substantial amount of water. Martian interior can also provide
      microbial cryptolife with sources of carbon (CO, CO2, CH4) and energy (reduced
      elements and compounds, e.g. H2, CO, H2S, NH4+, CH4, Fe3+). Microorganisms
      identical to the Earth's anaerobic methanogens, sulfate reducers, acetogens,
      denitrifiers etc. are the most probable Martian aborigines. Well-balanced
      continuous functioning of the Martian cryptobiosphere implies closure of
      biochemical carbon, sulfur and nitrogen cycles which cannot be reached but with
      participation of organotrophic and anaerobic hydrolytic and zymotic organisms,
      ammonifiers and denitrifiers. Considering the low intensity of biological and
      chemical processes in the absence of surface hydrosphere, low-power atmosphere
      and cryptobiosphere closure on Mars, and slow global energy matter cycles,
      evolution of the presumable Martian cryptolife should also go at a slack pace and
      directions and forms of the evolution of living substance can have little in
      common with those on Earth. Comprehensive investigations of the Martian biota
      will employ a great variety of geochemical, radi- and stable isotope,
      microbiological, enzymatic and molecular biology methods.

PMID- 14730729
TI  - [Biomedical support to a piloted Martian expedition].
AB  - Review of the main problems of biomedical support (BMS) to a piloted mission to
      Mars has revealed a correlation of the BMS constituents and parameters with the
      specifics of this venture that makes it significantly different from the near
      Earth flights. Success of the transit to Mars and back and safety of the planet
      explorers will hinge on the BMS system functionality in the harsh changing
      environment and power to ensure medical safety, health and performance of the
      crew. Particular emphasis has been placed on the necessity to enhance methods of
      crew selection and training, to develop an on-board medical center including an
      appropriate database, to search for high-efficiency countermeasures, to formulate
      prescriptions for resolution possible psychological problems in flight, and to
      design and manufacture regenerative life support and radiation protection
      systems.

PMID- 14730730
TI  - [Several clinical aspects of a piloted Martian flight].
AB  - The authors consider factors and risk sources in long and superlong
      (interplanetary) missions, conceivable effects of extended exposures in
      microgravity, and probability of diseases in the crew. They also lay down the
      basic principles of medical care, including surgery, to be applied in the
      interplanetary mission, and propose a nomenclature of key means and equipment for
      the therapeutic and emergency medical care, and a configuration of a medical
      compartment.

PMID- 14730731
TI  - [The problem of creation of artificial gravity with the use of a short-radius
      centrifuge for medical support of interplanetary piloted missions].
AB  - On the evidence of orbital flights, the system of countermeasures against the
      effects of microgravity does not fully make for deconditioning of a number of
      human organs and systems and recovery of preflight physical status and working
      ability of members of long-term missions takes 1.5 to 2 mos. of the post-flight
      rehabilitation. In order to maintain the physical form, health and performance of
      crews in future interplanetary missions, we should be ready to offer them a novel
      countermeasure, i.e. regular sessions of artificial gravity generated by a short
      radius centrifuge (SRC) on board vehicles. The articles presents the
      substantiation and concept of ground-based simulation studies of health benefits
      from SRC in interplanetary missions. Of primary concern is development of SRC
      regimens that will put up a strong opposition to microgravity, assure crew
      safety, and reduce to the minimum time to fulfill the in-flight countermeasure
      program. Answers to arising questions can be found by consolidation of the
      expertise and resources of the countries willing to meet this challenge.

PMID- 14730732
TI  - [An expert system for controlling the physical training program of crews on long
      term space missions].
AB  - The concept of in-flight expert system for controlling (ESC) the physical
      training program during extended, including Martian, space missions has been
      developed based on the literature dedicated to the microgravity countermeasures
      and a retrospective analysis of effectiveness of the known ESC methods. This
      concept and the principle of crew autonomy were used as prime assumptions for
      defining the structure of ESC-based training in long-duration and planetary
      missions.

PMID- 14730733
TI  - [A mission to Mars: the prognostic analysis of concurrent psychological
      problems].
AB  - Psychological implications of situations that may take place during a mission to
      Mars including desynchronosis, fatigue, psychic asthenization, acute mental
      disorders, interruption of the information flow, unpredicted transformation of
      the socio-psychological needs, a persistent conflict tension in the crew, errors
      in manual control of the vehicle, refusal or impossibility to fulfill an
      operation, difficulties in communication between the crew and ground controllers
      were analyzed for determination of their causes and consequences, probable
      starting time, ways and methods of preventing and surmounting each of these
      situations.

PMID- 14730734
TI  - [Problems of radiation safety of a Martian expedition crew].
AB  - Analysis of the radiation conditions during a piloted expedition to Mars made it
      evident that the radiation safety system will be one of the most critical
      components of life support aboard the future Martian vehicle. The concept and
      main functions of the system have been considered. The authors give their vision
      of the radiation monitoring system based on the present-day radiation safety
      postulates, comparison and contrasting methods and equipment applied for the
      purpose in current orbital and projected interplanetary flights.

PMID- 14730735
TI  - [The concept of microbiological safety of a piloted Martian expedition].
AB  - It is the peculiar evolution of the microbial association aboard long-operating
      space vehicles that lends additional medical, technical and technological risks
      that may impact crew safety and orbital systems performance. Based on the
      experience of the Russian space stations, a concept of microbiological safety of
      a piloted expedition to Mars has been proposed comprising preventive measures,
      methods, means and technologies to control the microbiological environment in
      transport vehicles, lander and Martian habitation module.

PMID- 14730736
TI  - [Ways of creating a nutrition system for a Martian expedition crew].
AB  - Approaches to a more perfect system of food supply to a Martian crew have been
      outlined in view of the experience of providing food stuffs for orbiting crews.
      Considering the extended period of the autonomous interplanetary voyage during
      which the humans should stay healthy and effective, development of especially
      lavish menu and methods to maintain food quality throughout the mission become
      critical. These are the two conditions to be met in order to provide the crew
      with balanced diets and fully satisfy needs of their organism.

PMID- 14730737
TI  - [Biological processes of the human environment regeneration within the Martian
      crew life support systems].
AB  - Five ground-based experiments at RF SRC-IBMP had the purpose to make a thorough
      investigation of a model of the human-unicellular algae-mineralization life
      support system. The system measured 15 m3 and contained 45 liters of alga
      suspension; the dry alga density was 10 to 12 g/l and water volume (including the
      alga suspension) amounted to 59 l. More sophisticated LSS models where algae were
      substituted by higher plants (crop area in the greenhouse equaled 15 m2) were
      investigated in three experiments from 1.5 mos. to 2 mos. in duration. It was
      found that the alga containing LSS was able to fulfill not only the macrofunction
      (air and water regeneration) but also several additional functions (air
      purification, establishment of microbial cenosis etc.) providing an adequate
      human environment. This polyfunctionality of the biological regenerative
      processes is a weighty argument for their integration into space LSSs. Another
      important aspect is that the unicellular algae containing systems are highly
      reliable owing to a huge number of species-cells which will be quickly recovered
      in case of the death of a part of the population and, consequently, functionality
      of the LSS autotrophic component will be restored before long. For an extended
      period of time the Martian crew will have no communication with the Earth's
      biosphere which implies that LSS should be absolutely reliable and redundant.
      Redundancy can be achieved through installation aboard the vehicle of two systems
      constructed on different principles of regeneration, i.e. physical-chemical and
      biological. Each of the LSSs should have the power to satisfy all needs of the
      crew. The best option is when two systems are functioning in parallel sharing the
      responsibility for the human environment. Redundancy in this case will mean that
      in the event of failure or a drastic decrease in performance of one system the
      other one will make up for the loss by increasing its share in the overall
      regeneration process.

PMID- 14730739
TI  - The Medicare bill.

PMID- 14730738
TI  - [Development of a technology for biodegradation of plant wastes in order to
      resolve the life support requirements of a Martian expedition].
AB  - A two-phase technology has been developed for biodegradation of plant wastes. On
      the first phase, wastes are subjected to anaerobic fermentation by specially
      selected microbial associations processing solid wastes into a liquid mixture of
      organic acids. On the second phase, methanogenic bacteria are used to produce
      biogas out of the liquid, which then can be dumped out into open space or
      utilized as a cold propellant.

PMID- 14730740
TI  - The battle for tort reform 2003.

PMID- 14730741
TI  - Is the cost of medical malpractice litigation rising faster than inflation?

PMID- 14730742
TI  - New Jersey Medicine, now and in the future.

PMID- 14730743
TI  - E-prescribing technology can improve patient care. The handwriting on the wall.

PMID- 14730744
TI  - Dorothea Lynde Dix. "My first-born child".

PMID- 14730745
TI  - Healthcare: a profession of the heart.

PMID- 14730746
TI  - Nursing ethics--an introduction.

PMID- 14730747
TI  - ASNA independent study activity--substance abuse and the older adult.

PMID- 14730759
TI  - Early psychological intervention: a word of caution.
AB  - The second Gulf War and liberation of Iraq have spawned new fears of domestic
      terrorism. There have been numerous calls for the integration of disaster mental
      health services into extant public health and national defense policies
      (Holloway, Norwood, Fullerton, Engel & Ursano, 1997; DiGiovanni, 1999; Susser,
      Herman, & Aaron, 2002, August). While most agree that such a strategy is
      warranted, questions abound as to how the tactical components should be
      implemented. Furthermore, concern has been raised regarding the importance of
      "doing no harm" (NIMH, 2002), i.e., the risk of iatrogenic harm. This article,
      while acknowledging the potential value of early psychological intervention,
      acknowledges the potential risks associated with the form of emergency mental
      health intervention, often referred to as crisis intervention. The article also
      provides suggestions for reducing the risks for iatrogenic harm associated with
      crisis intervention.

PMID- 14730760
TI  - Major misconceptions in crisis intervention.
AB  - Crisis intervention and its subset, Critical Incident Stress Management, have
      experienced a century of successful application across a broad spectrum of
      populations. Numerous positive outcome studies including Randomized Controlled
      Trials, controlled studies, and detailed literature reviews attest to its
      achievements. The success of crisis intervention services has not, however, gone
      without critical reviews. Some reviews have, unfortunately, generated a series of
      misconceptions and factual misrepresentations. This article presents some of the
      most common misconceptions and offers arguments to counter those errors.

PMID- 14730761
TI  - Fear of terrorism in New York after the September 11 terrorist attacks:
      implications for emergency mental health and preparedness.
AB  - To examine the public's response to future terrorist attacks, we surveyed 1,001
      New Yorkers in the community one year after the September 11 attacks. Overall,
      New Yorkers were very concerned about future terrorist attacks and also concerned
      about attacks involving biological or nuclear weapons. In addition, while most
      New Yorkers reported that if a biological or nuclear attack occurred they would
      evaluate available information before evacuating, a significant number reported
      they would immediately evacuate, regardless of police or public health
      communications to the contrary. The level of public concern was significantly
      higher on all measures among New York City and Long Island residents (downstate)
      compared to the rest of the state. A model predicting higher fear of terrorism
      indicated that downstate residents, women, those 45 to 64 years old, African
      Americans and Hispanics, those with less education/income, and those more likely
      to flee, were more fearful of future attacks. In addition, making disaster
      preparations and carefully evaluating emergency information also predicted a
      higher level of fear as well. A second model predicting who would flee suggested
      that those more likely to evaluate available information were less likely to
      immediately evacuate, while those with a higher fear of future attacks were more
      likely to flee the area. Given these findings and the possibility of future
      attacks, mental health professionals need to be more involved in preparedness
      efforts, especially related to the psychological impact of attacks involving
      weapons of mass destruction.

PMID- 14730762
TI  - Large group crisis intervention for law enforcement in response to the September
      11 World Trade Center mass disaster.
AB  - University Behavioral HealthCare, University of Medicine and Dentistry of New
      Jersey in partnership with the New Jersey Department of Personnel established a
      program entitled "Cop 2 Cop" in 1999 to assist law enforcement personnel within
      the state. The events of September 11, 2001, demanded an unprecedented response
      to address the behavioral health care needs of those individuals in New Jersey
      and New York. Although the Cop 2 Cop program was initiated as a crisis
      intervention hotline, the legislature which established the program also
      identified facilitating Critical Incident Stress Management services for New
      Jersey law enforcement and their families as needed to be within the scope of
      function. This paper describes the Cop 2 Cop program interventions with the Port
      Authority Police Department (PAPD) which involved service provision to over 1,200
      PAPD officers and an intensified process entitled an "Acute Stress Management
      Reentry Program" created for over 200 officers with unprecedented exposure to
      traumatic events.

PMID- 14730763
TI  - My life since my head injury.
AB  - Nancy Bauser describes her experiences as a brain injury survivor and her quest
      to recover. After surviving an automobile accident in 1971, Bauser relearned how
      to walk, talk, and function independently. Despite her physical limitations, she
      completed undergraduate studies and her graduate degree in social work. Her
      current work includes peer counseling and conducting acceptance groups with
      survivors of brain injury and other traumatic disorders at outpatient treatment
      facilities.

PMID- 14730764
TI  - '2003--a big year in the portfolio of evidence supporting midwives and
      midwifery'.

PMID- 14730765
TI  - Hepatitis B vaccine at birth--just another barrier to breastfeeding?

PMID- 14730766
TI  - Sound critical appraisal of the research literature is vital in assessing the
      evidence for interventions.

PMID- 14730767
TI  - Midwifery dilemma: to fast or feed the labouring woman. Part I: The case for
      restricting oral intake in labour.
AB  - This paper presents a literature review which pursues both sides of the labouring
      woman's oral intake debate--to fast or to feed the labouring woman. Part 1
      provides an exploration of the phenomenon of gastric content aspiration
      associated with general anaesthesia and its historical and physiological
      underpinnings. Part 2 provides an examination of the literature concerning the
      benefits of fasting labouring women.

PMID- 14730768
TI  - Overcoming the undersupply--supporting midwives' return to practice.
AB  - The current critical shortage of midwives is a worldwide phenomenon that has
      created the need for educational programs that prepare midwives, who have
      previously left midwifery practice, for return to the contemporary clinical
      workforce. This paper focuses on the support requirements of midwives involved in
      a refresher program as determined by a research project conducted at The Northern
      Hospital in Melbourne during 2001. The project was a small-scale case study
      involving eight program participants. Questionnaires and semi-structured
      interviews were used to generate data. Analysis of the data revealed that the
      concept of support must be considered from personal and professional
      perspectives, if successful outcomes are to be achieved. INTRODUCTION: The
      response of the Federal Government to the dire shortage of midwives currently
      working in public healthcare facilities has been to allocate funding to the
      states and territories for education and re-skilling programs, with the aim of
      enticing midwives back to clinical practice (Walsh 2001). In Victoria, refresher
      programs have been developed to meet the needs of midwives whose level of
      expertise has diminished due to lack of clinical experience, but who have
      fulfilled the necessary requirements.

PMID- 14730769
TI  - From student to midwife: the experiences of newly graduated midwives working in
      an innovative model of midwifery care.
AB  - In 2001, a new model of midwifery care was established in the Birth Centre at St
      George Hospital, a metropolitan hospital in NSW. The new model was designed to
      encompass the principles and recommendations from numerous government reports and
      research. The model also build on the previous successful implementation of a
      team midwifery program (Homer et al 2001b; Homer et al 2001a). Four newly
      graduated midwives, together with four more experienced midwives were employed to
      work in the models of midwifery care. This small study evaluates the first 10
      months' using qualitative and quantitative data. As this is a small study, no
      firm conclusion can be reached. The results of the evaluation however
      demonstrated that with appropriate support and mentoring, newly graduated
      midwives can work in an innovative model of midwifery care within a birth centre
      environment.

PMID- 14730770
TI  - Collecting client data: a phenomenological study of midwives' experiences.
AB  - This phenomenological study explored the experiences of a small group of South
      Australian midwives engaged in client data collection within a unique midwifery
      triage model. Gadamerian hermeneutic principles guided data collection through
      unstructured interviews with the midwives and the identification of key themes.
      Findings included a philosophy of dialogue, the dynamics of dialogue, protection
      and advocacy issues and individual practices and concerns.

PMID- 14730771
TI  - The development of National ACMI Standards for the accreditation of three-year
      Bachelor of Midwifery programs.
AB  - Prior to 2002 Australians who wished to become midwives were expected to complete
      and undergraduate nursing degree and then apply for admission to a university
      based post-nursing program in midwifery, usually requiring an additional year of
      study. Graduates were, therefore, qualified to practice in either profession.
      Many organisations, coalitions and individuals have contributed to the arduous
      struggle to ensure that midwives are educated in ways that allow them to
      confidently and competently fulfill their role as the World Health Organisation
      defines it. Indeed, in some states, universities and Nurses Boards recognising
      the need for multiple routes of entry to practice have introduced three-year
      undergraduate midwifery degrees. So far this has taken place in South Australia
      and Victoria but other states intend to follow this initiative. In this paper the
      background to the development of the ACMI National Bachelor of Midwifery
      Taskforce and the midwifery Program Standards will be discussed. A brief
      description of the Program Standards is presented to show how they can be used to
      ensure that 21st century midwives are capable of competently and confidently
      responding to the changing needs of maternity service providers and consumers.
      Finally, the authors argue that it is crucial that employers and clinicians have
      access to a standardised, objective means to evaluate midwifery programs, and
      believe that the Standards provide the means to do this.

PMID- 14730772
TI  - Respond to the letter to the editor in the summer 2003 NJDA Journal from Dr.
      Bender.

PMID- 14730773
TI  - Circle of trust.

PMID- 14730774
TI  - He's no average Joe.  A conversation with assemblyman Joe Pennacchio, DDS. 
      Interview by Eric R. Elmore.

PMID- 14730775
TI  - Oral pathology quiz #41. Case number 1. Multiple myeloma.

PMID- 14730776
TI  - Oral pathology quiz #41. Case number 2. Melanotic macule.

PMID- 14730777
TI  - Oral pathology quiz #41. Case number. 3. Odontogenic keratocyst.

PMID- 14730778
TI  - Oral pathology quiz #41. Case number 4. Nasopalatine duct cyst.

PMID- 14730779
TI  - The overweight child in the dental chair: risk management considerations.

PMID- 14730780
TI  - Reflecting on the past year in nursing and planning the future.

PMID- 14730781
TI  - Renal assist device therapy for acute renal failure.
AB  - Acute renal failure (ARF) is a syndrome that occurs frequently in critically ill
      patients. Current treatments for ARF in the intensive care unit (ICU) include
      intermittent hemodialysis and continuous renal replacement therapies. These
      treatments provide for the replacement of some functions of the kidney, such as
      water and waste removal, but they do not provide the metabolic, immunologic or
      endocrine functions of the kidney. A new bioartificial kidney device has been
      developed that appears to more completely replace the functions of the failed
      kidney and is termed the Renal Assist Device (RAD). This article will describe
      the syndrome of ARF and the use of the RAD device, currently in clinical trials
      in critically ill patients with ARF.

PMID- 14730782
TI  - Renal homeostasis of calcium.
AB  - Calcium is critical for many metabolic functions. While 99% of body calcium is
      found as part of the structure of bone and teeth, 1% found in plasma and body
      cells is crucial for such functions as blood clotting, nerve impulse conduction,
      and muscle contraction. The homeostasis of calcium is complex because the
      gastrointestinal tract, the bones, and the kidneys all affect calcium balance.
      This manuscript reviews the functions, homeostasis, and renal handling and
      regulation of calcium. The major sites of renal tubular reabsorption and the
      related cellular mechanisms are described.

PMID- 14730783
TI  - Fatigue among caregivers of chronic renal failure patients: a principal
      components analysis.
AB  - Quality of life for caregivers of ESRD patients has not been well addressed. The
      physical and psychological status of this overlooked group can be important in
      the recovery or adaptation of patients with chronic renal failure. One particular
      symptom of a reduced quality of life of such caregivers is that of fatigue. The
      study tested the reliability of both existing and newer fatigue measures.
      Measures with high reliability yielded a single construct of fatigue in a
      principal components analysis in this study of 99 caregivers. Implications for
      practice are addressed. Potential for further study is recommended.

PMID- 14730784
TI  - Optimizing nutrition in patients with chronic kidney disease.
AB  - Nutrition is a crucial part of the treatment of patients with chronic kidney
      disease (CKD) because of its influence on morbidity and mortality. Nutrition
      status can be assessed using laboratory nutrition markers, the Subjective Global
      Assessment (SGA), anthropometric data, diet interviews and food diaries, and
      psychosocial assessment. Diet prescriptions need to be individualized based on
      each patient's degree of CKD and type of renal replacement therapy.

PMID- 14730785
TI  - Resources for planning palliative and end-of-life care for patients with kidney
      disease.
AB  - Historically, Americans have died of infectious diseases, often in childhood or
      young adulthood. Cancer has also been responsible for thousands of deaths. With
      the advent of improved antibiotics and chemotherapy, people are surviving much
      longer and many, especially those over 65 years of age, will incur at least one
      chronic disease or disability in their lifetime. As the health care emphasis has
      changed from intervening for acute illness to treating the adverse effects of
      chronic disease, our health care system has also somewhat shifted gears. Unlike
      serious acute illness, chronic illness generally does not lead to a swift death
      in a hospital, but rather to a prolonged course of symptom management in the home
      setting or a long-term care facility. In some situations, the patient or family
      are battling a disease process where death is inevitable. Although holding on for
      a cure, the patient and family may begin considering the option of a dignified
      and peaceful death. In the care of renal patients, nephrology nurses have an
      expanded and important role in assisting patients with their decisions concerning
      palliative and end of life care and in providing that care. Fortunately,
      resources are now available to assist with the coordination of a therapeutic plan
      of care.

PMID- 14730786
TI  - Tune up your data collection skills!

PMID- 14730787
TI  - Treating pediatric nephrotic syndrome: a clinical challenge.

PMID- 14730788
TI  - National symposium special interest group presentations: transplantation.

PMID- 14730789
TI  - Laboratory data evaluation: how does the renal dietitian interpret results?

PMID- 14730790
TI  - The uncertain future of continuing medical education: commercialism and shifts in
      funding.
AB  - To preserve a professionally responsible system for continuing medical education
      (CME), medicine must recognize and address two powerful economic forces:
      commercial interests and societal resource limitations. Commercial support to
      accredited CME providers is now more than 50% of total CME income. The cumulative
      influence is increasingly biasing CME development, presentation, and
      participation toward topics that benefit commercial interests. Options to address
      this cumulative bias are proposed. Limitations on societal resources for health
      care have reduced funding from medical schools and hospitals for the
      infrastructure of CME. Financial pressures are likely to increase, potentially
      leading to controls on drug costs and significant reductions in commercial
      support of CME. Financial pressures on physicians' incomes may limit the extent
      to which registration fees could offset these reductions. Physicians and their
      professional organizations should recognize these threats to the objectivity,
      funding, and infrastructure of the CME system and they should work to ensure a
      viable CME system in the future.

PMID- 14730791
TI  - Health systems research training enhances workplace research skills: a
      qualitative evaluation.
AB  - INTRODUCTION: In-service education is a widely used means of enhancing the skills
      of health service providers, for example, in undertaking research. However, the
      transfer of skills acquired during an education course to the workplace is seldom
      evaluated. The objectives of this study were to assess learner, teacher, and
      health service manager perceptions of the usefulness, in the work setting, of
      skills taught on a health systems research education course in South Africa and
      to assess the extent to which the course stimulated awareness and development of
      health systems research in the work setting. METHODS: The education course was
      evaluated using a qualitative approach. Respondents were selected for interview
      using purposive sampling. Interviews were conducted with 39 respondents,
      including all of the major stakeholders. The interviews lasted between 20 and 60
      minutes and were conducted either face to face or over the telephone. Thematic
      analysis was applied to the data, and key themes were identified. RESULTS: The
      course demystified health systems research and stimulated interest in reading and
      applying research findings. The course also changed participants' attitudes to
      routine data collection and was reported to have facilitated the application of
      informal research or problem-solving methods to everyday work situations.
      However, inadequate support within the workplace was a significant obstacle to
      applying the skills learned. DISCUSSION: A 2-week intensive, experiential course
      in health systems research methods can provide a mechanism for introducing basic
      research skills to a wide range of learners. Qualitative evaluation is a useful
      approach for assessing the impacts of education courses.

PMID- 14730792
TI  - Women physicians are early adopters of on-line continuing medical education.
AB  - INTRODUCTION: On-line continuing medical education (CME) provides advantages to
      physicians and to medical educators. Although practicing physicians increasingly
      use on-line CME to meet their educational needs, the overall use of on-line CME
      remains limited. There are few data to describe the physicians who use this new
      educational medium; yet, they clearly are the innovators and early adopters who
      will facilitate the growth of this educational technology. It would be useful to
      instructional designers and CME developers to better understand the
      characteristics of this influential group. METHODS: We studied the actual use of
      several different on-line CME programs within three different groups of
      physicians. The on-line programs were developed as part of research studies
      funded by the National Institutes of Health, with no relationship to commercial
      interests. They were presented to physicians using mass mailouts (two physician
      groups) or personal contact and were accompanied by incentives to reduce
      resistance to the new technology. We compared the characteristics of physicians
      who chose to use these on-line programs with demographic data from larger
      populations representing the groups from which these users originated. RESULTS:
      We found that physicians who used these on-line CME programs were younger than
      average and, importantly, more likely to be female than expected. This finding
      was consistent across different types of physician populations and different
      types of CME programs. DISCUSSION: Based on data reflecting actual use of on-line
      CME, younger physicians appear to be adopting on-line CME more rapidly than
      others, and women physicians appear to be adopting on-line CME at a faster rate
      than their male counterparts. This latter finding conflicts with the impression
      provided by some survey-based studies that male physicians are more likely than
      female physicians to use on-line CME. The data suggest that the growth of on-line
      CME is most likely occurring in diffusion networks dominated by relatively new
      medical school graduates and, possibly, women physicians. These results provide
      valuable insight to those who seek to develop and market on-line CME and those
      who seek to reach women physicians with CME programs.

PMID- 14730793
TI  - Discourse analysis of computer-mediated conferencing in World Wide Web-based
      continuing medical education.
AB  - INTRODUCTION: Computer-mediated conferencing (CMC) is a computer messaging system
      that allows users to engage in asynchronous text-based communications that are
      independent of time and place. It has been suggested that CMC is an effective
      modality for facilitating constructivist learning environments that enable adult
      learners to engage in a continuous, collaborative process of building and
      reshaping knowledge and understanding. The goals of this exploratory study were
      to assess the nature of the interactions and collaborative learning
      characteristics exhibited in World Wide Web-based continuing medical education
      courseware programs that used CMC and to examine physicians' satisfaction with on
      line CMC discussion as a planned learning activity of Web-based CME. METHOD: The
      Transcript Analysis Tool (TAT) was used to analyze the nature of the discourse
      that took place in four different Web-based CME courseware programs. Course
      evaluation surveys and interviews were also conducted with participants to
      evaluate their satisfaction with on-line CMC discussion. RESULTS: The results
      suggest that the nature of participation in the programs consisted primarily of
      independent messages with a minimal amount of learner-to-learner interaction.
      Elements of critical reflection, interaction, and debate between participants
      appeared to be missing from these discussions. As such, these discussions were
      not characteristic of the principles of constructivist learning environments.
      DISCUSSION: Interactive participation will not occur just because CMC is being
      used. The design of Web-based CME learning activities, participant
      characteristics, and facilitation are key factors that influence the effective
      use of CMC.

PMID- 14730795
TI  - Continuing medical education and continuing medical education accreditation in
      Spain.
AB  - Nearly all Spanish physicians are employed by public or private institutions, and
      employers are enabling the continuing medical education (CME) of physicians. In
      view of coexisting CME accreditation systems in Spain, we conclude that a common
      approach is needed. We recommend establishing formal relationships with American
      and European systems to ensure consistent accreditation and mutual recognition of
      CME credits and improvement in accreditation.

PMID- 14730794
TI  - Short-term educational intervention improves family physicians' knowledge of
      depression.
AB  - INTRODUCTION: Depression is frequently unrecognized and undertreated. Therefore,
      there is a need to increase the knowledge and skills of primary care physicians
      regarding management of depression. The aim of this study was to determine if a
      brief educational intervention can affect family physicians' knowledge of the
      diagnosis and treatment of depression. METHOD: Sixty-eight community-based,
      nonacademic family physicians completed the program, which was delivered using a
      mixed lecture-seminar format. Knowledge about depression was assessed pre- and
      post-program. Paired-sample t test and chi-square test were used to compare test
      scores. RESULTS: Although study physicians demonstrated high baseline knowledge
      of depression, 75% of them had better scores following the program. The increase
      in knowledge was statistically significant (p < .0001). DISCUSSION: Our study
      demonstrates that a simple and brief educational program can enhance family
      physicians' knowledge of depression; however, an increase in knowledge alone may
      not necessarily translate into practice behavior change.

PMID- 14730796
TI  - Using a technological community framework to manage new medical technologies. The
      case of umbilical cord blood (UCB) banking.
AB  - A technological community framework can be used to explain and manage new medical
      technologies. It describes emergence, commercialization, and standardization of
      an innovation or technology within the context of its whole network (or
      community) of stakeholders. This framework is used to illustrate the emergence,
      commercialization, and standardization of a relatively new medical technology-
      umbilical cord blood (UCB) banking. Umbilical cord blood may prove to be a source
      of stem cells for bone marrow transplant that is safer, more accessible, and less
      expensive than current sources of stem cells. The technological community
      framework can signal potential problems as the technology emerges, and help
      healthcare delivery systems and providers to effectively assess and manage the
      technology. The framework can also be applied to other medical technologies and
      innovations.

PMID- 14730797
TI  - Family-friendly policies: general nurses' preferences and experiences.
AB  - While European Union policy emphasises that one of the aims of family-friendly
      working arrangements is to increasing gender equality, in the UK the focus has
      been primarily on workforce retention. Drawing on a study of Registered General
      Nurses who returned to work after breaks for maternity leave, this paper
      considers their preferences and experiences in light of current UK family
      friendly policies and the implications of the findings for increasing gender
      equality. Questionnaires were completed by respondents in three regional health
      authorities and focused on the four to eight year period after qualification. The
      following topics were investigated: views about length of maternity break and
      reasons for returning to work sooner than preferred; hours sought after a return
      and hours obtained; the availability of preferred patterns of work and of
      flexible hours; retention of grade on return; the availability and use of
      workplace creches, and childcare arrangements when children were unwell.

PMID- 14730798
TI  - Downsizing in the public sector: Metro-Toronto's hospitals.
AB  - This study has two objectives. First, to predict the outcomes of a public sector
      downsizing; second to measure effects of downsizing at organizational and inter
      organizational levels. Primary data to assess the organizational level effects
      was collected through interviews with senior executives at two of Metro-Toronto's
      hospitals. Secondary data, to assess the inter-organizational effects, was
      collected from government documents and media reports. Due to the exploratory
      nature of the study's objectives a case study method was employed. Most
      institutional downsizing practices aligned with successful outcomes. Procedures
      involved at the inter-organizational level aligned with unsuccessful outcomes and
      negated organizational initiatives. This resulted in an overall alignment with
      unsuccessful procedures. The implication, based on private sector downsizings, is
      that the post-downsized hospital system was more costly and less effective.

PMID- 14730800
TI  - Fundamental shortcomings of evidence-based medicine.
AB  - The development of any scientific theory has a certain logic. Bruno Latour
      formulated a theory, describing the development of science and technology.
      Outcomes of science are not guided by nature or "the truth", but by a complex
      negotiation. It starts with ideas, which follow paths of publications and
      assessment. Then they are either rejected or accepted. Analysing the development
      of evidence-based medicine with Latour's theory, we find two fundamental
      problems. First, EBM tends to standardise moral considerations. Second, EBM
      standardises the patient, since test populations are usually composed
      homogeneously. Presumptions concerning methods and morals are slid into the EBM
      methodology during its development. With Latour we should say, that the
      conceptions of the standard patient and standard morals have been delegated to
      this methodology. They are carried out strictly, and this causes the discomfort
      with practitioners and scientists within EBM. A solution should be sought for in
      redesigning trials, in a less morally charged fashion, and concerning less
      standardised patients.

PMID- 14730799
TI  - Managerial skills of principal physicians assessed by their colleagues. A lesson
      from Finland.
AB  - The purpose of this paper was to discover the views of doctors regarding the
      managerial skills of their principal physicians and the views of doctors of their
      postgraduate specialist training in management. This was done by sending out a
      questionnaire to every second physician registered in 1977-1986 in Finland. They
      were asked to evaluate their principal physician's managerial skills using a
      visual analogue scale. A five-point Likert scale was used to inquire how much
      training doctors had received for different professional tasks, including
      management, during their specialist training. Of all the 318 principal physicians
      in this study, 85 percent reported that they had had too little training for
      managerial skills. It was found that doctors in leading positions, both in public
      hospitals and the primary health care sector, are aware of the need of training
      for managerial and leadership skills.

PMID- 14730801
TI  - Want to have input? Consider a professional Practice Council in your workplace!

PMID- 14730803
TI  - Advance directives for artificial nutrition and hydration. One lesson from the
      Terry Schiavo case.

PMID- 14730804
TI  - The road to recovery continues.

PMID- 14730808
TI  - Online nursing continuing education a new tool at the ONA Website.

PMID- 14730811
TI  - Fertility assumptions for the 2002-based national population projections.
AB  - One of the key components of national population projections is the assumed level
      of fertility, which determines the number of future births in the projections.
      Assumptions are made in terms of the average number of children women will have
      over their lifetime. For the 2002-based projections this average is assumed to
      ultimately be 1.75 for England and for Wales, 1.60 for Scotland, and 1.80 for
      Northern Ireland, leading to a United Kingdom assumption of 1.74. This article
      explains how these overall assumptions, which are the same as assumed in the 2000
      based and interim 2001-based projections, are derived. It also explains why these
      levels are higher than current 'period' indicators of fertility. Finally,
      information on more detailed age specific fertility rates, and implications for
      family size distributions, is given.

PMID- 14730809
TI  - Fear factor: treating fear in the hospitalized client.

PMID- 14730812
TI  - Changes in the distribution of marital age differences in England and Wales, 1963
      to 1998.
AB  - Assumptions about the 'typical' age gap between spouses underlie much social
      policy (e.g. the five-year difference in men's and women's state pension ages).
      In order to test the basis for these assumptions, detailed marriage registration
      statistics were obtained for 1963 and 1998, for England and Wales. Age
      differences between spouses were calculated and analysed by year, age at marriage
      and previous marital status. The median age gap hardly changed between 1963 and
      1998 but this concealed considerable increase in the proportion of marriages
      where the man was younger than the woman or--to a lesser extent--where the man
      was six or more years older.

PMID- 14730813
TI  - Unmarried parenthood: new insights from the Millennium Cohort Study.
AB  - This study uses information from the Millennium Cohort Study to examine the
      characteristics of families where children are born within a marriage, within a
      cohabiting union or outside of a co-residential partnership. For this latter
      group, for the first time in a national data set, an assessment can be made of
      the 'strength' of the parent's relationship at the time of the birth. We show
      that the context of childbearing varies with respect to geography, ethnicity,
      age, parity and educational status of the mother, and that the socioeconomic
      wellbeing of families varies according to the partnership status of their
      parents. A closer look at the non-partnered parents shows that the extent to
      which the fathers were involved with the mother of the child around the time the
      baby was born was related to the presence of the father at the birth of the child
      and whether his name was recorded on the child's birth certificate; as well as to
      subsequent behaviour, such as, whether they moved in with the mother, saw their
      children on a regular basis or contributed money to the child's maintenance.

PMID- 14730815
TI  - A new crisis for the med mal market?
AB  - Medical malpractice insurance loss costs are surging, insurers are quitting the
      business, and doctors are threatening to leave their practices. Is med mal on the
      verge of a major new crisis? This article explores the genesis of the current
      crisis and attempts to provide some perspective that may be helpful inviewing the
      situation.

PMID- 14730814
TI  - Summary of final changes to EMTALA regulations.
AB  - The Emergency Medical Treatment and Labor Act (EMTALA) was enacted in 1986. Its
      purpose was to ensure that all individuals receive necessary emergency services
      from hospitals and not be denied care (i.e., "patient dumping") because of their
      economic status or lack of insurance. In its application, EMTALA has reduced
      "patient dumping," but at great cost to hospitals and physicians as an unfunded
      mandate. Despite 17 years of experience with the law, providers have been
      uncertain as to where and when, and to whom, the EMTALA obligations apply. The
      law has also proven to be burdensome and has been interpreted as extending far
      beyond the hospital emergency room. After reviewing the law for some time, the
      Centers for Medicare and Medicaid Services (CMS) released its final rules
      redefining the scope of EMTALA, reaffirming certain guidelines and modifying or
      clarifying others. The new regulations attempt to restate the parameters of the
      law as it applies to the emergency department and the hospital, as well as to
      inpatients and outpatients. The new rules clarify on-call obligations for
      physicians, confirming guidance issued by CMS in June 2002. This article
      summarizes the salient features of these new regulations.

PMID- 14730816
TI  - The electronic medical record in multi-site family practice. Part II: The
      implementation phase.
AB  - Electronic medical records are being successfully implemented on a regular basis.
      They provide real benefits. This is a detailed explanation of how this medical
      group implemented and created a paperless medical practice environment and an
      electronic medical record (EMR). This includes an explanation of hardware and
      software components, the method of creating the EMR, the benefits, pitfalls, and
      the impact on the practices.

PMID- 14730817
TI  - Patient flow and the revenue cycle.

PMID- 14730819
TI  - Preliminary screening of job applicants in five steps.
AB  - If you receive a gargantuan response to your next help-wanted ad, take heart.
      Having too many job applicants need not be a problem if you take a little time to
      do some preliminary screening. In this article, the author suggests a five-step
      screening technique that will help you identify the best applicants from a large
      pool. Specifically, the article explains how to eliminate unsuitable candidates
      and offers practical guidelines for ranking qualified applicants. It also offers
      advice about verifying job eligibility and using skill tests in the application
      process. Finally, the author offers seven specific characteristics to look for
      when conducting brief telephone screening interviews with job candidates, as well
      as additional tips for making your screening process most effective.

PMID- 14730818
TI  - Developing personnel policies to keep you out of the courtroom: the role of the
      office policy manual.
AB  - Employment liability has become an important issue for all enterprises. Medical
      practices often are not aware of the impact their policies and actions may have
      on their employees and the liability that may result. This article surveys this
      important area of human resource management and provides some guidelines to avert
      potential pitfalls.

PMID- 14730820
TI  - Guidelines for corporate covenants and physician employment agreements.
AB  - Failure to set forth an appropriate framework for collaboration and employment
      between physicians can be the source of much distress and acrimony. This article
      details some guidelines based on the author's consulting practice that will help
      physicians structure corporate or partnership agreements and terms of employment
      that are fair and clear.

PMID- 14730821
TI  - Making your encounter form work for you.
AB  - Practices depend on proper coding of procedures and diagnoses to obtain maximal
      reimbursement. Proficient coding by both educated physicians and staff is
      dependent on transmission of correct information. A well-designed encounter form
      is one key to enhance the process. This article provides some practical
      guidelines for making the encounter form more effective.

PMID- 14730822
TI  - The investment pyramid: give due consideration to risk-reward ratios and capital
      liquidity.
AB  - In spite of constraints in reimbursement and relatively flat incomes in many
      specialties for the last decade, most physicians can still look forward to
      significant incomes over their professional lives. Hopefully, they may accumulate
      sufficient funds for retirement. In the interim, the management of their
      resources has become evermore difficult with the vagaries of investment results
      over the past three years. This article details the authors' views to a balanced
      approach to structuring one's financial position with a focus on insurance and
      general investment options.

PMID- 14730823
TI  - CPT new patient vs. established patient guidelines.

PMID- 14730824
TI  - Supreme Court says treating physician's opinion not entitled to deference under
      ERISA.

PMID- 14730825
TI  - The regulatory morass: physicians' dealings with pharmaceutical manufacturers.

PMID- 14730826
TI  - Development of a patient satisfaction survey for outpatient care: a brief report.
AB  - Patient satisfaction has become a significant component of health care outcomes
      and an increasingly important component of quality assessment. Selecting the
      appropriate methods to measure patient satisfaction is a critical challenge for
      health care managers, yet, there is limited knowledge of the methods used to
      develop patient satisfaction instruments. In this brief report, we provide
      insights into the development of a patient satisfaction instrument for outpatient
      care at the Duke Private Diagnostic Clinic (PDC). We surveyed the 12 medical
      directors and asked them to rate 15 concept areas for inclusion in an outpatient
      satisfaction survey. We then constructed a patient satisfaction survey by drawing
      selected subscales from the publicly available PSQ-18 (Patient Satisfaction
      Questionnaire) and CAHPS (Consumer Assessment of Health Plans) surveys to address
      the seven highest rated concept areas: 1) general/overall satisfaction; 2)
      courteousness of office staff; 3) courteousness of physicians; 4) doctor/patient
      communication; 5) professionalism; 6) ease and time to get appointment; and 7)
      technical quality of care.

PMID- 14730827
TI  - Bipolar nurse alleges discrimination for mental disability.

PMID- 14730828
TI  - Nurse addicted to stadol sues manufacturer. Case on point: Uhiren v. Bristol
      Myers Squibb Company, Inc., 346 F.3d 824--AR (2003).

PMID- 14730829
TI  - NY: nurse learns of pt's doubt re surgery site: hospital liabile for operation on
      wrong hand.

PMID- 14730830
TI  - GA: failure to monitor infant-neurological injury: nurse not liable for
      deprivation of oxygen, etc.

PMID- 14730831
TI  - Failure to keep inmate on meds results in further amputation. Case on point:
      Wilson v. Manning, 2003 WL 22418424 So.2d--AL.

PMID- 14730832
TI  - X-rays in emergency settings.

PMID- 14730833
TI  - Radiating abdominal pain with constipation and diarrhea.

PMID- 14730834
TI  - Gliding higher. NP salaries ascend at a steady pace.

PMID- 14730835
TI  - Differential diagnosis of abdominal pain in women of childbearing age.
      Appendicitis or pelvic inflammatory disease?

PMID- 14730836
TI  - Soothing the burn. Management of gastroesophageal reflux disease.

PMID- 14730837
TI  - Patient information. Pediatric reflux: a burp gone bad.

PMID- 14730838
TI  - Quick asthma assessment. A stepwise approach to treatment.

PMID- 14730839
TI  - Sensory integration dysfunction. Recognition in primary care settings.

PMID- 14730841
TI  - Taking the plunge.

PMID- 14730840
TI  - Pediatric obesity. Family's role essential to treatment.

PMID- 14730842
TI  - Two important keys: autonomy and working together.

PMID- 14730843
TI  - Marion's message. From Mexico.

PMID- 14730844
TI  - What does instinctive birth mean to you? How do you facilitate it?

PMID- 14730845
TI  - A vision of birth.

PMID- 14730846
TI  - Being a midwife.

PMID- 14730847
TI  - Preparing the nest.

PMID- 14730848
TI  - Instinctive birth: finding the pulse.

PMID- 14730849
TI  - The art of leaving alone.

PMID- 14730850
TI  - Listening to Eve.

PMID- 14730851
TI  - Birth as sheer pleasure.

PMID- 14730853
TI  - The ties that bind. How belief creates birth realities.

PMID- 14730852
TI  - Voices of distress. Women speak about cesarean sections.

PMID- 14730854
TI  - Midwifery etiquette.

PMID- 14730855
TI  - Breastfeeding during pregnancy. Moving from fear to instinct.

PMID- 14730856
TI  - Transports: making a seamless transition.

PMID- 14730857
TI  - Women in birth.

PMID- 14730858
TI  - Effective alternative treatments for breech presentation.

PMID- 14730859
TI  - To progress or not to progress.

PMID- 14730860
TI  - The day Dorian was born.

PMID- 14730861
TI  - Salt of the earth. Homeopathic Natrum muriaticum.

PMID- 14730862
TI  - Healing in Mexico.

PMID- 14730863
TI  - Hungarian women unveil an ironic curtain.

PMID- 14730864
TI  - Instinctual breech birth.

PMID- 14730865
TI  - Interviews with maiden midwives. Reaching out to the next generation. Interview
      by Mary Kroeger.

PMID- 14730866
TI  - Evidence-based midwifery. Listening to fetal heart tones.

PMID- 14730867
TI  - [Elective operative procedures in patients with chronic end-stage renal failure].
AB  - The results of 92 elective operative interventions, performed in 71 patients with
      chronic renal insufficiency (CRI) in terminal stage, were studied. Performance of
      elective operative interventions in patients with CRI in terminal stage, to whom
      the treatment, using chronic hemodialysis, was conducted, allows to increase
      quality of their medical and social rehabilitation considerably and the efficacy
      of kidney transplantation (KT). They constitute effective and safety method of
      treatment in complex surgical program of patients preparation to KT performance.

PMID- 14730868
TI  - [Twenty year experience in the treatment of peritonitis, multiple organ
      dysfunction syndrome in perforative ulcers].
AB  - The results of treatment of 573 patients, operated on the clinic for the period
      from 1981 to 2000 year for perforative gastroduodenal ulcer were analyzed. In 24
      (4.2%) of them the necessity of relaparotomy performance for peritonitis,
      polyorgan insufficiency had occurred. In all patients complex intensive therapy,
      intestinal decompression, flowing peritoneal dialysis were conducted, in 10--the
      governed laparotomy. In 9 patients plasmapheresis was performed, in 8--drainage
      of ductus thoracicus with lymphosorption, in 7--xenosorption. Application of
      complex treatment equally with active detoxication in patients with peritonitis,
      polyorgan insufficiency have allowed to achieve recovery in 66.6% of them.

PMID- 14730869
TI  - [Micro-organism translocation and acute anastomosis inflammation after stomach
      resection].
AB  - The results of examination of 42 patients with an acute anastomositis after
      performance of gastric resection were analyzed. Clinical classification was
      elaborated for detailed interpretation of the anastomosits diagnosis and choice
      of therapy. Close correlative inter-relatioship between severity of anastomositis
      and degree of gastric mucosa colonization by micro-organisms was established
      basing on analysis of the laboratory and bacteriological investigations results.

PMID- 14730870
TI  - [Prevention of post-burn scarring esophageal strictures, strategies of surgical
      treatment].
AB  - Experience of treatment of 52 patients with oesophageal chemical burn in acute
      and early postburn period was analyzed, as well as in 649--with oesophageal
      postburn cicatricial stricture (OPCS). In 18 patients perforation of esophagus
      had occurred during performance of bougienage. Rational complex of diagnostic and
      therapeutic measures in such patients was determined. The results of bougienage
      in patients with OPCS were summarized. Causes of the oesophageal perforation
      occurrence during bougienage were analyzed. Tactics of surgical treatment of
      esophageal perforation was determined. Analysis of the treatment results and of
      the main causes, which conditioned upon the postoperative complications
      occurrence, was conducted.

PMID- 14730871
TI  - [Nonspecific pleural exudate and pleural layer injury: epidemiologic, etiologic
      and patho-anatomic aspects].
AB  - Modern epidemiologic data about prevalence and etiology of the nonspecific
      pleural exudates syndrome were suggested in patients of phthisio-pulmonary
      specialty, and also its dynamic during last 7 years. The main trends of change of
      frequency of the different etiology pleural exudates occurrence taking into
      account the patients gender were determined. The most wide spread forms of
      pleural exudates: parapneumonic, purulent, reactive, phthisic, cardiogenic were
      detailed.

PMID- 14730872
TI  - [Diagnostic laparoscopy and treatment choice in patients with closed abdominal
      injuries].
AB  - The results of laparoscopic investigations, conducted in 94 injured persons with
      preliminary diagnosis of closed abdominal trauma were analyzed. Of them in 47 the
      damage of internal organs was excluded. In an emergent order there were operated
      on 47 patients. Splenectomy was performed in 28 patients (including 2--in whom
      simultaneously the hepatic and pancreatic lacerations were closed by sutures),
      cholecystectomy--in 3, cholecystostomy, drainage of bursa omentalis--in 1,
      resection of small intestine--in 2, resection of omentum--in 1, closure of the
      small intestine wounds with sutures--in 3, of the bladder with epicystostomy
      performance--in 2, of the small intestine mesentery--in 2, of the liver--in 1,
      drainage of bursa omentalis--in 1, opening of infrahepatic abscess--in 1,
      examination of retroperitoneal hematoma with drainage--in 2.

PMID- 14730873
TI  - [Analysis of fatal outcomes in severe nonpenetrating thoracic and abdominal
      injuries].
AB  - Experience of treatment of 1147 injured persons with severe closed
      thoracoabdominal trauma (SCTT) in acute period was summarized. Analysis of causes
      of the injured persons deaths was conducted, irreversible states in SCTT were
      determined. Lethality had constituted 33.4%.

PMID- 14730874
TI  - [Malignant hormonally inactive adrenal tumors: aspects of diagnosis and
      treatment].
AB  - Application of computer tomography (CT) and other modern methods of topic
      diagnosis have permitted to reveal "silent" adrenal tumors more frequently. To
      conduct a timely and radical treatment it is necessary to estimate the stage of
      malignancy and hormonal activity of these tumors. There were analyzed the results
      of treatment of 90 patients with malignant hormonally--inactive adrenal tumor.
      The size of the tumor, as well as data of CT and magnetic resonance tomography
      constitutes the criterions, determining the malignant origin of the tumor and
      indications for operation performance. Application of fine-needle aspiration
      puncture biopsy is indicated for diagnosis of presumably metastatic adrenal
      affection. The open extraperitoneal lumbotomic adrenalectomy is the only radical
      method of treatment of adrenal malignant tumor. For diagnosis of presumably
      malignant epinephric affection application of endoscopic technique is
      contraindicated.

PMID- 14730875
TI  - [Modified surgical treatment of rectal atresia with rectovaginal fistula].
AB  - In our clinics in 1992-2002 89 girls with anorectal developmental anomaly
      underwent modified perineal proctoplasty. In 65 (73.3%) patients the rectal
      atresia with vestibular fistula was revealed, in 17 (19%)--vaginal fistula, 7
      (7.7%)--perineal fistula. After modified perineal proctoplasty carry out the good
      result is achieved in 37 (85%) patient, satisfactory one--in 6 (13%),
      nonsatisfactory (incontinence of feces)--in 1 (2%).

PMID- 14730876
TI  - [Dynamic biliary manometry: display modelling and graphic interpretation].
AB  - Tendencies of development of biliary manometry have been analyzed. Key advantages
      and problems of manometric investigation of biliary tracts have been summarized.
      New method of graphic registration and pressure monitoring in biliary tracts
      called biliary manometry has been suggested. Characteristic types of manometric
      curves were determined using stand modelling, their physical and mathematical
      analysis was conducted, clinical analogues have been suggested. The emphasis has
      been made on expediency of its further elaboration and clinical application.

PMID- 14730877
TI  - [Aspects of cooperation between the pathologist and the surgeon].

PMID- 14730878
TI  - [The role of interaction of neutrophil granulocytes, endothelial cells and
      mononuclear macrophages in pyo-sepsis. Report 3. Structural and functional
      peculiarities and mechanisms of interaction of "neutrophil granulocyte
      endothelial cells"].

PMID- 14730879
TI  - [Vibratory dilator].

PMID- 14730880
TI  - [Leiomyosarcoma of the abdominal aorta aneurysm].

PMID- 14730881
TI  - [The influence of splenic artery ligature on the severity of portal gastropathy
      in patients with hepatic cirrhosis].

PMID- 14730882
TI  - [Rare observation of pulmonary xanthogranuloma].

PMID- 14730883
TI  - [Endoscopic laser recanalization of decompensated cicatricial tracheal stenosis].

PMID- 14730884
TI  - [Atypical course of acute appendicitis].

PMID- 14730885
TI  - [Dyshormonal cyst of mammary gland].

PMID- 14730886
TI  - [Mistakes in diagnostics and treatment of pancreatic cyst in children].

PMID- 14730887
TI  - [Reflux esophagitis with esophageal peptic stenosis and splenic ectopy after
      correction of congenital diaphragmatic hernia and Nissen fundoplication].

PMID- 14730888
TI  - [Choristoma of the thyroid gland in children].

PMID- 14730889
TI  - [Bullous pulmonary emphysema: salvaging resection with additional local
      application of biological adhesive].

PMID- 14730890
TI  - [mRNA expression alteration of two-pore potassium channels in the brain of beta
      amyloid peptide25-35-induced memory impaired rats].
AB  - AIM: To study mRNA expression alteration of two-pore potassium channels in the
      brain of beta-amyloid peptide25-35 (beta-AP25-35)-induced memory impaired rats.
      METHODS: Memory impairments induced in rats by single icv injection of beta-AP25
      35 (2 mmol.L-1) 5 microL were assessed in the Morris water maze test. The mRNA
      expression levels of three two-pore potassium channels TREK-1, TREK-2 and TRAAK
      were detected in rat cerebral cortex and hippocampus by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: In the Morris water maze test, the
      escape latencies of the beta-AP25-35-treated rats were longer than those of the
      control group in 1st, 2nd and 4th training day, suggesting that the memory of
      beta-AP25-35-treated rats was obviously impaired. Compared with the control
      group, the mRNA levels of TREK-1, TREK-2 and TRAAK in the hippocampus of the beta
      AP25-35-treated rats were increased by 40.0%, 27.9% and 18.9%, respectively;
      while no significant change of TREK-1, TREK-2 and TRAAK mRNA levels was observed
      in the cortex. CONCLUSION: The mRNA expression levels of two-pore potassium
      channels were increased significantly in the brain of beta-AP25-35-induced memory
      impaired rats.

PMID- 14730891
TI  - [Protective effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)
      propane hydrochloride(DDPH) on brain ischemia injury in rats].
AB  - AIM: To study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4
      dimethoxyphenylethylamino) propane hydrochloride(DDPH) on brain ischemia injury
      in rats. METHODS: By using the middle cerebral artery occlusion (MCAO) induced by
      nylon surgical thread inserted through the internal carotid artery into the
      anterior cerebral artery in rats, the effects of DDPH on neuron defects(ND) and
      infarct size(IS) were investigated. Using incomplete cerebral ischemia in rats,
      the effects of DDPH on superoxide dismutase (SOD) activity and malondialdehyde
      (MDA) content in brain tissue and pathological changes in rats were studied.
      RESULTS: DDPH at the dose of 10 mg.kg-1 i.p. 30 min before ischemia decreased the
      ND 3 h after ischemia. The IS declined 24 h after ischemia as well. Meanwhile,
      DDPH was found to increase SOD activity and reduce the MDA content, as well as
      mitigate pathological damage, of neuron after brain ischemia in rats. CONCLUSION:
      DDPH showed protective effects on brain ischemia, probably related to its
      properties of calcium antagonistic effect and increasing the activity of
      superoxide dismutases.

PMID- 14730892
TI  - [Effect of esculentoside A on cellular adhesion].
AB  - AIM: To investigate the anti-inflammatory mechanism of esculentoside A (EsA) and
      to observe the effects of EsA on cellular adhesion between human umbilical vein
      endothelial cell (VEC304) and human neutrophil and to further observe the mRNA
      expression of intercellular adhesion molecule-1 (ICAM-1) and cluster of
      differentiation 18(CD18). METHODS: The hemocyte counting method was used for
      assaying the adhesion rate between VEC304 and neutrophil. The RT-PCR method was
      used for measuring the mRNA expression of ICAM-1 and CD18. RESULTS: The adhesion
      rate between VEC304 and neutrophil was increased with treatment of
      lipopolysaccharide(LPS). EsA (3 - 12 x 10(-6) mumol.L-1) was shown to inhibit the
      high cellular adhesion induced by LPS. A further investigation of adhesion
      molecules mRNA expression was undertaken using semi-quantitative reverse
      transcribed polymerase chain reaction (RT-PCR). The results of RT-PCR from VEC304
      and human neutrophil treating with LPS showed that ICAM-1 and CD18 mRNA
      expressions were higher than those of normal cells, while this increased
      expression of ICAM-1 and CD18 mRNA was remarkably attenuated by the addition of
      EsA. CONCLUSION: EsA was found to inhibit the increased adhesion rate induced by
      LPS. Moreover, LPS induced high expression of ICAM-1 and CD18 was inhibited with
      treatment of EsA. It might be involved in the mechanisms of anti-inflammation of
      EsA.

PMID- 14730893
TI  - [Novobiocin inhibits angiogenesis and shows synergistic effect with vincristine].
AB  - AIM: To study the anti-angiogenic activity of novobiocin and its mechanism of
      action. METHODS: The anti-angiogenic activity of novobiocin was determined using
      chick embryo chorioallantoic membrane(CAM) assay. MTT assay, zymography and
      related assays were used to observe the effects of drugs on bovine aorta
      endothelial cells and human pulmonary carcinoma PG cells. RESULTS: Novobiocin at
      the doses of 100 and 200 micrograms/egg inhibited angiogenesis by 31.6% and 68.7%
      in CAM, respectively. The combination of novobiocin and vincristine enhanced the
      anti-angiogenic effect. Novobiocin inhibited the proliferation of bovine aortic
      endothelial cells in a concentration-dependent manner. In addition, novobiocin
      suppressed MMP-2 secretion, migration, and tube formation of endothelial cells.
      As determined by MTT assay, novobiocin in combination with vincristine displayed
      synergistic effect on the proliferation of PG cells, CONCLUSION: This study
      demonstrates that novobiocin is active in suppressing angiogenesis and the anti
      angiogenic activity may be enhanced by combination with vincristine. The anti
      angiogenic activity of novobiocin may be related, at least in part, to its
      inhibition of cell proliferation, cell migration, tube formation and secretion of
      matrix metalloproteinases.

PMID- 14730894
TI  - [Culture of neural stem cells from cerebral cortex of rat embryo and effects of
      drugs on the proliferation ability of stem cells].
AB  - AIM: To establish culture procedures of neural stem cells from embryonic rat
      brain, determine their stem-cell characteristics and observe the effects of
      several compounds on their proliferation ability. METHODS: Firstly, a stem cell
      culture system was set up from embryonic rat cortex. The cells were identified as
      neural stem cells through immunocytochemistry, in which antibodies to neural stem
      cell specific protein and markers of mature neural cells were used. Then, by
      using MTT assay, the survival rate of neurospheres incubated with various
      concentrations of ginsenoside Rg1, (-)-clausenamide and salvianolic acid A were
      observed. Furthermore, the effect of these drugs was measured with 3[H] thymidine
      incorporation assay. RESULTS: In this study, a culture model of neural stem cell
      was successfully set up. In this model, primary cells from E16-18 rat cortex were
      dissected out, and cultured as floating neurospheres. The results of
      immunocytochemistry showed that nestin was expressed by the majority of cells
      within the sphere. After growing for 8 days in differentiation medium, cells from
      a single neurosphere were shown to differentiate into 3 main kinds of neural
      cells: neurons, astrocytes and oligodendrocytes. MTT assay revealed that the
      three drugs all enhanced the survival rate of neural stem cells, but 3[H]
      thymidine incorporation assay suggested that only Rg1 significantly accelerated
      the proliferation rate. CONCLUSION: One culture model of neural stem cell was set
      up successfully. Meanwhile, several drugs were found to increase the
      proliferation and/or survival rate of neural stem cells. It has been demonstrated
      that neural stem cells exist in adult mammalian brains. So, these drugs may
      become promising candidates for the therapy of neurodegenerative diseases; such
      as Alzheimer's disease and Parkinson's disease.

PMID- 14730895
TI  - [Effects of caspases on cerebromicrovascular endothelial cell apoptosis induced
      by hypoxia].
AB  - AIM: To study the effects of caspases on cerebromicrovascular endothelial cell
      apoptosis induced by hypoxia in vitro. METHODS: The cultured bovine
      cerebromicrovascular endothelial cells were exposed to NaCN in glucose-free
      medium. Cell viability was determined by trypan blue staining. Cell apoptosis was
      defined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) and flow cytometry. The expression of caspase-3 was detected by
      immunocytochemical method. Four caspase inhibitors were used to validate the
      effect of caspases on cell apoptosis. RESULTS: NaCN in glucose-free medium
      initiated cerebromicrovascular endothelial cell injury markedly and typical
      apoptotic cells were found in this model. The expression of caspase-3 increased
      significantly. Four caspase inhibitors decreased the number of injured cells.
      Selective inhibitor of caspase-1 and -6 reduced expression of caspase-3
      significantly. CONCLUSION: The results suggest that caspases family plays an
      important role in cerebromicrovascular endothelial cell apoptosis induced by NaCN
      and caspase-3 acts on the downstream of caspase-1 and -6 in protease cascade
      action to induce apoptosis.

PMID- 14730896
TI  - Protection of organic trauma in sinoaortic-denervated rats treated with
      fosinopril.
AB  - AIM: To study the importance of blood pressure variability in organ protection
      for long-term treatment with fosinopril in-sinoaortic-denervated (SAD) rats.
      METHODS: Fosinopril (15 mg.kg-1.d-1) was given in rat chow for 16 weeks after SAD
      surgery. Blood pressure variability (BPV) was recorded during 24 h in conscious
      state. Histopathological changes were evaluated with light microscope and
      computer-assisted image analysis. RESULTS: Long-term treatment with fosinopril
      significantly decreased BPV in SAD rats. The thickness of the left ventricular
      wall, collagen fraction of the left ventricle and glomerulosclerosis score were
      all positively related to BPV in untreated and fosinopril-treated SAD rats.
      Fosinopril markedly prevented the damages of target organs in SAD rats.
      CONCLUSION: Long-term treatment with fosinopril showed obvious organ protection
      in SAD rats. The decrease in BPV may significantly contribute to organ
      protection.

PMID- 14730897
TI  - Synthesis and pharmacology of 8-amino-3-[(tetrahydro-2-furanyl)methyl]
      benzomorphan.
AB  - AIM: To design and synthesize new chiral 8-(substituted) amino-analogues of 3
      [(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the
      structure-activity relationship (SAR) for 8-aminobenzomorphan. METHODS: Target
      compounds were synthesized from the 8-triflate of the optically active 3
      [(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed
      aminations. Opioid receptor binding experiments were performed to evaluate their
      biological activities. RESULTS: Both 8-amino and 8-phenylamino analogues showed
      lower binding affinity for mu, delta and kappa receptors than corresponding 8
      hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.
      CONCLUSION: The relative poor binding affinity of the target compounds did not
      warrant conducting the in vivo studies to determine if they have the
      profile(kappa agonist/mu antagonist) that will be potentially useful in the
      treatment of drug addiction. Further study is in progress.

PMID- 14730898
TI  - [Synthesis and in vitro antibacterial activities of new 3,5-disubstituted
      oxazolidinone compounds].
AB  - AIM: To design and synthesize new oxazolidinone antibacterial agents. METHODS:
      The synthetic method reported in literature has been modified and new 3,5
      disubstituted oxazolidinone compounds were synthesized on the basis of SAR
      reported in the literature and their antibacterial activities in vitro were
      determined. RESULTS: Eighteen new objective compounds were synthesized, and their
      structures were determined by IR, 1HNMR and FAB-MS. Within the eighteen new
      objective compounds, sixteen compounds showed antibacterial activity in vitro and
      compound 9, 10 and 10b showed better antibacterial activities in vitro than
      ciprofloxacin (CIP), sultamicillin (Sul) and vancomycin (VCO). Compounds 9a and
      11c have no antibacterial activity in vitro at all. CONCLUSION: Compounds 9, 10
      and 10b are worthy to be intensively studied.

PMID- 14730899
TI  - [Chemical constituents of Cyanotis arachnoidea].
AB  - AIM: To investigate the chemical constituents of Cyanotis arachnoidea. METHODS:
      By using chromatographic methods for separation and combination with spectral
      analysis, their chemical structures were determined. RESULTS: Six compounds were
      identified as ajugasterone C-20, 22-acetonide (1), 20-hydroxyecdysone-20, 22
      acetonide (2), 22-oxo-ajugasterone C (3), 22-oxo-20-hydroxyecdysone (4), beta
      sitosterol (5), daucosterol (6). CONCLUSION: Compound 3 is a new compound, 4 was
      a new natural compound.

PMID- 14730900
TI  - [Studies on the chemical constituents from the aerial parts of Cimicifuga
      dahurica].
AB  - AIM: To seek for new bioactive constituents from the aerial parts of Cimicifuga
      dahurica. METHODS: Various column chromatographic techniques were employed for
      the isolation and purification of the ingredients. The structures were elucidated
      on the basis of 1H, 13CNMR, 1H-1H COSY, HMQC, NOESY and HMBC spectra and chemical
      reactions. RESULTS: Two cyclolanostanol xylosides, cimidahuside C and D were
      isolated from the EtOAc section of EtOH extracts. CONCLUSION: Cimidahuside C(1)
      and D(2) are new triterpenoid xylosides.

PMID- 14730901
TI  - [NMR studies on cetirizine hydrochloride].
AB  - AIM: To study the NMR phenomena of cetirizine hydrochloride and assign all proton
      and carbon signals in NMR spectra. METHODS: To record the 1D and 2D NMR spectra
      of cetirizine hydrochloride while changing the experimental temperature and
      adding D2O into the solution. RESULTS: More than one NMR signal or broad peak
      resulting from piperazine and the attached groups with N atom were given in DMSO
      d6 solution at room temperature. "Coalescence" or narrowing had occurred for the
      proton and carbon signals when the experimental temperature was increased or D2O
      was added into the solution. CONCLUSION: Compared with the NMR "time scale",
      there are more than one conformation of cetirizine hydrochloride in DMSO-d6
      solution at room temperature. The different conformation will be exchanged fast
      while temperature rise and the stable conformation will be existed while D2O was
      added into the solution.

PMID- 14730902
TI  - [Determination of danshensu in urine and its pharmacokinetics in human].
AB  - AIM: To determine Danshensu in urine and study its pharmacokinetics in human.
      METHODS: A solid phase extraction-HPLC method was used for determination of
      Danshensu in urine of human. HPLC separation is performed on a Shim-pack CLC-ODS
      column (150 mm x 6.0 mm ID, 5 microns) with a mobile phase composed of
      acetonitrile -0.01 mol.L-1 KH2PO4 (adjusted to pH 2.8 with phosphoric acid). The
      flow rate was 1.0 mL.min-1 and the UV detector was set at 280 nm. The linear
      range of Danshensu was 0.2-50 mg.L-1 (r = 0.9999), and its limit of detection was
      1.5 ng. The mean recovery was 99.4% (RSD = 2.9%). RESULTS: The pharmacokinetics
      of Danshensu after p.o. administration of two kinds of pharmaceutical
      preparations containing Danshen (with 20 mg of Danshensu) were investigated in 6
      healthy human volunteers by determining the Danshensu in urine samples. The
      elimination half lives (T1/2) of Danshensu after p.o. administration of compound
      granule preparation A and decoction of Danshen were (0.92 +/- 0.16) h and (0.94
      +/- 0.21) h, respectively. Their excretions of Danshensu in urine were (6.2 +/-
      2.8)% and (14 +/- 4)% of the dose in 8 hours, respectively. CONCLUSION: Under
      normal doses, Danshensu can be eliminated from kidney. There is no evident
      difference on elimination half lives of Danshensu after p.o. administration of
      the two doses, but the excretions of Danshensu by urine after p.o. administration
      of compound granule preparation A were lower than that of decoction of Danshen.

PMID- 14730903
TI  - Study on pharmacokinetics of scutellarin in rabbits.
AB  - AIM: To establish a solid phase extraction-high performance liquid
      chromatographic (SPE-HPLC) method for determining plasma scutellarin
      concentration, and study its pharmacokinetics after i.v. breviscapine in rabbits.
      METHODS: Methanol-water-phosphoric acid (50:50:0.5) mixture was used as mobile
      phase, Nucleosil C18 column (250 mm x 4.6 mm ID) was selected. The wavelength of
      UV detection was 335 nm. Fifteen rabbits, randomized into 3 groups, were given
      breviscapine i.v. at the dose of 10, 20 and 40 mg.kg-1. Scutellarin in plasma was
      determined by SPE-HPLC method. RESULTS: Linearity was obtained over the range of
      0.02-10.0 mg.L-1 of scutellarin. The method recovery was 96.15%-99.31%; the
      within-day and between-day RSDs were all below 10%. After i.v. 10, 20 and 40
      mg.kg-1 of breviscapine to rabbits, the concentration-time curve of scutellarin
      fitted to a three compartment model. The main pharmacokinetic parameters showed
      no significant difference between low and medium doses, but the difference was
      significant between high dose and other doses. CONCLUSION: This assay method was
      accurate, sensitive, simple and suitable for the measurement of plasma
      scutellarin concentration. The pharmacokinetic characteristics were found to fit
      a three-compartment model following i.v. injection of breviscapine to rabbits.
      The changes of drug concentration in vivo exhibited linear kinetics ove the
      dosage range of 10-20 mg.kg-1, but when the dosage was 40 mg.kg-1, the linear
      kinetic properties disappeared.

PMID- 14730904
TI  - [Precipitation reaction between berberine and rheinic acid by capillary
      electrophoresis].
AB  - AIM: To study the thermodynamics of precipitation reaction and kinetics between
      berberine and rheinic acid. The former is the main compound in rhubarb root or
      corktree bark, the latter is a representation of anthraquinone compounds that are
      the main kind compound in coptis rhizome. The precipitate produced in preparation
      of complex prescription of Chinese herbal medicines Xiexin decoction and Shaoyao
      decoction had made an appeal. The work should build a good basement for two
      decoctions research and development. METHODS: Capillary electrophoresis (CE) and
      front analysis methods are used for determining two compounds' equilibrium
      concentration at different precipitate conditions to calculate the constants of
      thermodynamics and kinetics. RESULTS: The molar ratio of berberine and rheinic
      acid in precipitate is 1:1. The solubility product constant Ksp = [B] [R] = (3.29
      +/- 0.19) x 10(-9) mol2.L-2. The precipitate reaction is an endotherm process and
      Ksp shows less effect by temperature. The reaction occurred immediately even
      though the precipitate cannot be observed in time. The precipitate process in
      experiments is practically just an aging or grown process of the precipitate
      particles. High temperature can quicken the aging. CONCLUSION: The precipitate in
      Chinese herbal medicines Xiexin decoction and Shaoyao decoction should be
      resulted from anthraquinone compounds and alkaloids. The reproductivity of
      capillary electrophoresis can be improved for simple sample by combining peak
      height measurement.

PMID- 14730905
TI  - [Establishment and application of in situ perfused pig ear model for percutaneous
      absorption].
AB  - AIM: To establish an in situ perfused pig ear model for percutaneous absorption.
      METHODS: The in situ perfused pig ear model for percutaneous absorption consisted
      of artificial gas, sample chamber, constant flow pump, constant temperature
      system, polytetrafluorethylene connective tube, porcine ear vein, porcine ear
      skin and special laminar flow apparatus. The perfused system viability was
      assessed by glucose utilization and lactate production. Ketoprofen isopropyl
      ester and methyl salicylate was used for validating this model. The
      concentrations of perfused sample were measured by HPLC. RESULTS: Glucose
      utilization and lactate production showed that this model was viable till 7 h.
      Ketoprofen isopropyl ester was completely metabolized to ketoprofen in situ in
      perfused pig ear model. The steady cumulative amount (Q) of ketoprofen from
      permeation and metabolism was linear with time (t), the equation of ketoprofen
      formation was Q = -0.024 + 0.120t, the rate of ketoprofen formation was 0.120
      microgram.cm-2.h-1. Methyl salicylate was partially metabolized to salicylic
      acid. The steady cumulative amount (Q) of methyl salicylate from permeation was
      linear with time (t), the permeation equation of methyl salicylate was Q = -3.809
      + 6.129t, the permeation rate of metyl salicylate was 6.129 micrograms.cm-2.h-1.
      The steady cumulative amount (Q) of salicylic acid from metabolism was also
      linear with time (t), the formation equation of salicylic acid was Q = -1.785 +
      0.879t, the formation rate of salicylic acid was 0.879 microgram.cm-2.h-1.
      CONCLUSION: The in situ pig ear vein perfused model is a novel easy-handing and
      cost-efficient technique for percutaneous absorption and skin metabolism.

PMID- 14730906
TI  - [Preparation of bovine serum albumin nanoparticles surface-modified with
      glycyrrhizin].
AB  - AIM: To study the preparation of bovine serum albumin nanoparticles surface
      modified with glycyrrhizin(BSA-NP-GL) targeting to hepatocytes. METHODS: The
      bovine serum albumin nanoparticles (BSA-NP) were prepared by desolvation process.
      Glycyrrhizin (GL) was oxidized by sodium periodate to be conjugated to surface
      reactive amino groups (SRAG) of the BSA-NP. The SRAG were quantified by
      spectrophotometric method using 2, 4, 6-trinitrobenzenesulfonic acid(TNBS).
      Glycyrrhetinic acid(GA) hydrolyzed from GL, which was on the surface of BSA-NP-GL
      was assayed by HPLC after isolation by sephadex G-50. Both methods were used to
      verify the conjugation achieved. HPLC was used to determine surface density of GL
      on BSA-NP-GL. RESULTS: The amount of SRAG of the BSA-NP-GL decreased by 19.6%
      compared with normal BSA-NP. The amount of GL molecule was 9.2% of the total
      determined SRAG of BSA-NP. The mean diameter of the BSA-NP-GL was 73 nm with
      round shape. The stability of BSA-NP-GL was constant when it was stored at 25
      degrees C and 37 degrees C during 10 days. CONCLUSION: BSA-NP-GL was successfully
      prepared, which is considered to establish an experimental foundation for further
      research on its ability for targeting to hepatocytes.

PMID- 14730907
TI  - [Comparative study of lipophilicity from immobilized artificial chromatography
      and n-octanol/buffer systems].
AB  - AIM: To compare lipophilicity measuring scale stemmed from immobilized artificial
      membrane chromatography and n-octanol/buffer systems. METHODS: A test set
      consisted of 27 structurally diverse compounds. The lipophilicity of these were
      evaluated by both immobilized artificial membrane chromatography (IAMC) and n
      octanol/buffer systems, which were expressed as lg kIAM and lg DO/W,7.4,
      respectively. RESULTS: With regard to each individual group, good correlation
      coefficient (r2) over 0.81 was obtained (0.82 for acid; 0.88 for neutral, 0.81
      for base and 0.92 for ampholyte, respectively). However, a smaller r2 (0.62) was
      acquired for all compounds studied than that of each individual group.
      CONCLUSION: IAMC and n-octanol/buffer systems were shown to be different in
      lipophilicity.

PMID- 14730908
TI  - [Application of biochip, genomics and proteomics in drug research and
      development].

PMID- 14730909
TI  - [Antithrombotic effects of morpholine and piperazine ring derivatives and their
      molecular mechanism].
AB  - AIM: To investigate the antithrombotic effects of morpholine and piperazine ring
      derivatives and their mechanisms. METHODS: In isolated rat aorta-precontracted
      with norepinephrine (NE), the vasodilatory effects of compounds with novel
      structure were investigated. Mice was given kappa-carrageenin i.p. and kept at
      the temperature of (20-21) degree C. RESULTS AND CONCLUSION: Active candidate
      compounds including MOPMC, 2FBMPC, MPTMBC, DMHPPP and PPVP were shown to
      antagonize thrombosis at the dose of 1 mg.kg-1 through activating the endothelial
      target for acetylcholine; while the contrasting compounds MAPC, 4C3FBMOC, mTBMPC,
      MONVP and MPNVP showed no significant effect on the tension of isolated aorta
      strips or significant antithrombotic effects at the same dose. The antithrombotic
      mechanism of novel compounds is not relevant to hemostatic systems or functions
      of platelet aggregation directly, but they can promote endothelial cells to
      release tissue-type plasminogen activator (t-PA) and inhibit the activity of
      plasminogen activator inhibitor-1 (PAI-1).

PMID- 14730910
TI  - [Pharmacokinetics of genistein in beagle dogs].
AB  - AIM: To study the pharmacokinetics of genistein in Beagle dogs. METHODS:
      Genistein, suspended in 0.5% CMC-Na solution, was orally administered to Beagle
      dogs at the dose of 5.34 mg.kg-1. At various time intervals, 1.5 mL of blood was
      drawn from the vein of dogs in their front legs. At the same time, urine and
      feces were collected. After the collection, the feces were homogenized with
      physiological saline (to 1 g feces, 10 mL physiological saline were added). The
      genistein in plasma, urine and homogenized feces was extracted twice by vortexing
      with 2.0 mL mixture of methyl tert-butyl ether and pentane (8:2). The organic
      phase was transferred into tubes and evaporated in ventilation cabinet. The
      residue was dissolved in 50 microL of methanol and 20 microL of the solution was
      drawn and detected by high-performance liquid chromatography. The pharmacokinetic
      parameter was calculated by 3P97 software. RESULTS: The plasma concentration-time
      curve was fitted to a one-open-compartment model. The peak time was 0.29 h, and
      the elimination half-life was 0.52 h. After genistein was administered, 10.79% of
      genistein were excreted from urine and 21.55% from feces within 24 h. It was also
      found that 13.00% genistein were excreted from urine and 52.46% from feces within
      60 h. CONCLUSION: It showed that the speed of absorption and elimination of
      genistein was high in Beagle dog, and genistein was mainly excreted in the form
      of parent compound in urine and feces.

PMID- 14730911
TI  - [Evodiamine induces A375-S2 cell death through two different pathways].
AB  - AIM: To study the mechanism of evodiamine-induced cell death of A375-S2. METHODS:
      The changes in cell morphology were observed by invert microscopy and Hoechst
      33258 staining. DNA fragmentation was assayed by agarose gel electrophoresis. The
      effects of evodiamine on apoptosis and cell cycle were studied by flow cytometric
      analysis. RESULTS: Evodiamine was shown to markedly inhibit the growth of A375-S2
      cells in dose- and time-dependent manners. At the early stage, evodiamine
      activated caspase cascades, which unexpectedly did not induce typical DNA
      fragmentation. At later stage, caspase inhibitors failed to block A375-S2 cell
      death induced by evodiamine. Evodiamine-induced cell death was shown to be not
      directly associated with cell cycle arrest. CONCLUSION: At the early stage,
      evodiamine initiates caspase-dependent and a typical apoptosis pathway in A375-S2
      cells, but later it induces cell death through caspase-independent pathway which
      might be necrosis.

PMID- 14730912
TI  - [Enzyme kinetics of clausenamide enantiomers in rat liver microsomes].
AB  - AIM: To investigate the enzyme kinetics of (-)3S,4R,5R,6S-clausenamide[(-)-Clau]
      and (+)-3R,4S,5S,6R-clausenamide[(+)-Clau] catalyzed by rat liver microsomes and
      compare their stereoselective differences. METHODS: An in vitro metabolic system
      was built by using rat liver microsomes and NADPH-generating system. Clau and its
      metabolites were determined simultaneously by a reversed-phase high performance
      liquid chromatography. The kinetic parameters, K(m), Vmax, and metabolic rate,
      Vmax/K(m), were calculated by Eadie-Hofstee plot. RESULTS: In the metabolic
      system, (-)-Clau was found to be mainly metabolized to 7-hydroxy-, 5-hydoxy- and
      4-hydroxy-Clau, and 7-hydroxylation was a preferential pathway which exhibited
      higher Vmax/K(m) value (0.135 microL.min-1.mg-1) than those of 5- and 4
      hydroxylation (0.063 and 0.068 microL.min-1.mg-1, respectively). For (+)-Clau, it
      was mainly metabolized to 4-hydroxy-Clau, whereas 7-hydroxy- and 4-hydroxy-Clau
      were so small that they could not be detected systematically. 4-Hydroxylation of
      (+)-Clau showed highest Vmam/K(m) value (0.547 microL.min-1.mg-1) among all the
      metabolites tested, which was 8.0 times higher than that of 4-hydroxylation of
      its antipode. CONCLUSION: The data indicated that there were obvious substrate
      stereoselective differences in the hydroxylation metabolism of (+)- and (-)-Clau,
      which provided an explanation of the difference of pharmacokinetic
      characteristics of Clau enantiomers in rats.

PMID- 14730913
TI  - [Effects of phenolic alkaloids of Menispermum dauricum on the hemodynamics and
      coronary circulation in anesthetized dog].
AB  - AIM: To observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD)
      on the hemodynamics, coronary circulation and oxygen metabolism of the myocardium
      in anesthetized dogs. METHODS: In this study, the changes of LVSP, LVEDP and +/-
      dp/dtmax, the flow of coronary artery and myocardial energy metabolism were
      measured in anesthetized dog with PAMD or NS. RESULTS: In the anesthetized dogs,
      compared with pre-treatment status, PAMD at 3.5 and 7.0 mg.kg-1 caused decreases
      in the left ventricular systolic pressure(LVSP), +/- dp/dtmax, heart rate, the
      rate of oxygen utilization, the coronary and general peripheral resistance. It
      was found to increase myocardial oxygen and coronary flow. There were no
      significant change in the left ventricular end diastolic pressure (LVEDP).
      CONCLUSION: PAMD can ameliorate hemodynamics, coronary circulation and myocardial
      metabolism.

PMID- 14730914
TI  - [Effects of interleukin-1 receptor antagonist on the apoptosis of eosinophil in
      guinea pig with asthma].
AB  - AIM: To evaluate the effect of interleukin-1 receptor antagonist(IL-1ra) on
      apoptosis and associated mechanism of eosinophil in guinea pig with asthma.
      METHODS: A model of guinea pig with asthma was established. After inhalation of
      different concentrations of IL-1ra, asthma was induced in the guinea pig for 8
      days, the concentration of eosinophil cationic protein (ECP) in serum and
      bronchoalveolar lavage fluid (BALF), IL-5 in serum, the eosinophil counts and
      apoptosis were assayed by radioimmunology, enzyme-linked immunosorbent
      assay(ELISA), fluoromicroscope and light microscope. RESULTS: IL-1ra indirectly
      decreased the level of IL-5 in serum, improved the apoptosis of eosinophil(EOS)
      in lung, then decreased the level of ECP in serum and BALF. CONCLUSION:
      Inhalation of nebulized IL-1ra showed protective effect against asthma through
      change of the activity and infiltration of EOS in lung.

PMID- 14730915
TI  - [Synthesis and antifungal activity of 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4
      diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols].
AB  - AIM: A series of triazole antifungals were synthesized to search for novel
      triazole antifungals with more potent activity, less toxicity and broader
      spectrum. METHODS: Nineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3
      (4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized,
      on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol
      demethylase (CYP51) and their antifungal activities were also evaluated. RESULTS:
      All the title compounds were first reported. Results of preliminary biological
      tests showed that most of the title compounds exhibited high activity against the
      eight common pathogenic fungi and the activities against deep fungi were higher
      than that against shallow fungi. CONCLUSION: Most of the title compounds showed
      higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1,
      10, 12, 17 showed best antifungal activity with broad antifungal spectrum and
      were chosen for further development.

PMID- 14730916
TI  - [Synthesis and anti-inflammatory activity of alpha-substituted p
      (methanesulfonyl)phenylpropenamides].
AB  - AIM: To search for new compounds with strong anti-inflammatory activity and low
      gastrointestinal (GI) side effects. METHODS: A series of alpha-substituted p
      (methanesulfonyl) phenyl-propenamides were synthesized. Their anti-inflammatory
      activities against xylene-induced mice ear swelling and carrageenan-induced rat
      paw edema were evaluated, and their GI side effects in rats were examined.
      RESULTS: Twenty-five target compounds (II1-25) were obtained, and their
      structures were determined by IR, 1H NMR, MS and elemental analysis. Thirteen
      compounds (II1,3,5,8-13,15,18,19,23) exhibited marked anti-inflammatory activity
      comparable to diclofenac sodium (DC) and rofecoxib (RC) in xylene-induced mice
      ear swelling model, and twelve compounds (II1,3,5,7,8,10-12,17,18,20,23) showed
      remarkable anti-inflammatory activity comparable to DC and RC in carrageenan
      induced rat paw edema. Compounds II3,8,10,11,18,20 showed GI side effects less
      than DC (P < 0.01), and no significant difference compared with RC and CMC-Na (P
      > 0.05). CONCLUSION: alpha-Substituted p-(methanesulfonyl)phenylpropenamides
      showed strong anti-inflammatory activity but few GI side effects and deserve to
      be further investigated.

PMID- 14730918
TI  - [Studies on the chemical constituents of Angelica sinensis].
AB  - AIM: To investigate the chemical components of Agelica sinensis. METHODS:
      Chromatographic technologies were used for separation and purification, while
      spectral analysis was measured for structure elucidation. RESULTS: Five compounds
      were isolated and their structures were identified as Homosenkyunolide H (1),
      Homosenkyunolide I(2), Neoligustilide (3), 6-methoxycoumarin (4), Hypoxanthine-9
      beta-D-ribofuranoside (5). CONCLUSION: Compounds 1 and 2 are new compounds.
      Compounds 3, 4 and 5 were isolated from Agelica sinensis for the first time.

PMID- 14730917
TI  - [A new alkaloid from Opuntia vulgaris].
AB  - AIM: To study the chemical constituents of the stems of Opuntia vulgaris
      Mill(Cactaceae). METHODS: The compounds of Opuntia vulgaris were isolated by
      chromatography of Amberlite Dowex 50 and silica gel, and identified by means of
      UV, IR, MS, 1D and 2D NMR. RESULTS: Three compounds were isolated and identified
      as: opuntin B(I), 4-hydroxyproline(II) and tyrosine(III). CONCLUSION: Compound I
      is a new alkaloid.

PMID- 14730919
TI  - [Quality control of recombinant adeno-associated virus type 2/human blood
      coagulation factor IX].
AB  - AIM: To establish quality control requirements and methods for recombinant adeno
      associated virus(rAAV) type 2/human blood coagulation factor IX (rAAV-2/hFIX).
      METHODS: Identification of rAAV genome fragments, potential contaminants
      including wild type AAV(wtAAV) and helper virus, were detected by PCR. Purity of
      rAAV-2/hFIX was analyzed by cation-exchange HPLC and SDS-PAGE. Virus partical
      numbers were performed by dot blot assay. hFIX expression was demonstrated by
      ELISA and potency of hFIX was verified by APTT. RESULTS: Identity of rAAV-2/hFIX
      was proved. Residues of wtAAV and helper virus were conformed to requirements.
      Purity of rAAV-2/hFIX were more than 98%. Partical numbers of rAAV-2/hFIX were
      more than 1.0 x 10(15) VG.L-1. hFIX expression was more than 20.0 micrograms.L-1.
      hFIX potency was verified by APTT following rAAV-2/hFIX injected to FIX gene
      knockout mice, potency results conformed to requirements. CONCLUSION: The methods
      and requirements had been established for quality control of rAAV-2/hFIX.

PMID- 14730920
TI  - [Nucleoside from Cordyceps kyushuensis and the distribution of two active
      components in its different parts].
AB  - AIM: To rapidly separate and determine the nucleosides from natural and cultured
      Cordyceps kyushuensis Kob., and to compare the content of cordycepin and
      adenosine in different parts of Cordyceps kyushuensis Kob., which are the main
      nucleoside active components in medicinal fungus belonging to Cordyceps (Fr.)
      Link. METHODS: The nucleosides were separated and determined by the high
      performance capillary zone electrophoresis (CZE). Beckman P/ACE system MDQ
      apparatus equipped with a PDA detector and a uncoated fused-silica capillary (41
      cm x 45 microns ID, 30 cm effective length) were used. The experimental
      conditions were as follows: the running buffer was borax solution (adjust to pH
      9.4 with sodium hydroxide), applied voltage was 20 kV, operated temperature was
      20 degrees C and the detector wavelength was 258 nm. The content of cordycepin
      and adenosine in the fruiting body, stroma and host worm of natural and cultured
      C. kyushuensis were respectively investigated and quantitatively analyzed.
      RESULTS: There are at least 8 kinds of nucleoside or nitrogen base in Cordyceps
      kyushuensis Kob. The content of cordycepin which is a bio-active substance with
      anti-tumor activity in C. kyushuensis is significantly higher than that in C.
      sinensis and C. militaris, and furthermore the cordycepin in the cultured C.
      kyushuensis is notably higher than the natural one. Adenosine was mainly found
      from the stroma of C. kyushuensis, While the cordycepin content is high in the
      stroma of both natural and cultured C. kyushuensis as well as in the host worm of
      the cultured one. CONCLUSION: There are some differences about the nucleoside
      components between the natural and cultured C. kyushuensis and between the
      different parts of them. With a high cordycepin content, C. kyushuensis should
      have a considerable medicinal potential.

PMID- 14730921
TI  - [Analysis of the response factors of different quinolones detected by evaporative
      light-scattering detector].
AB  - AIM: To analyze the response factors of different quinolone antibiotics detected
      by evaporative light-scattering detector (ELSD). METHODS: The response factors of
      five different quinolones (enoxacin, levofloxacin, ciprofloxacin, lomefloxacin
      and gatifloxacin) detected by ELSD were determined by using a YMC-Pack ODS-AM
      cloumn (150 mm x 4.6 mm ID, 5 microns) as analytical column and 0.5%
      triethylamine (adjusting pH 2.5 with trifluoroacetic acid)-acetonitrile (48:12)
      as mobile phase at a flow rate of 0.6 mL.min-1, the temperature of the drift tube
      was set at 117 degrees C, and the flow of carrier gas at 3.0 L.min-1. Detector
      responses (A) and the amount of injection of each substance (m) were fitted to
      the logarithmic regression: log A = b log m + log a. RESULTS: The linear
      regression equation obtained were: enoxacin: Y = 1.0799X + 2.7611, r2 = 0.9996;
      levofloxacin: Y = 1.0913X + 2.7235, r2 = 0.9997; ciprofloxacin: Y = 1.0828X +
      2.7523, r2 = 0.9994; lomefloxacin: Y = 1.0891X + 2.7391, r2 = 0.9993;
      gatifloxacin: Y = 1.0878X + 2.7392, r2 = 0.9995. The differences between them
      were negligible. CONCLUSION: Different quinolones can give the same responses
      with ELSD detection. So, the HPLC-ELSD methods can be applied to the
      determination of new substances by using another substance as reference.

PMID- 14730922
TI  - [Cationic lipid and polyethylene glycol enhance liposomes-mediated cell
      transfection and increase the fluidity of liposomes membranes].
AB  - AIM: To prepare fluorescein sodium (FS) cationic liposomes and investigate the
      influence of cationic lipid (DC-chol) and polyethylene glycol (PEG) with
      different molecule weight (MW) on cationic liposome incorporation efficiency,
      cellular delivery and fluidity of liposome membrane. METHODS: Using FS as a model
      material for encapsulation, the liposomes were prepared and separated (by
      sephadex G-50 1 cm x 20 cm column), and the liposome incorporation efficiencies
      was measured. The interaction between the FS and cationic liposomes was
      investigated by measuring the change of fluorescent spectrum. The cellular uptake
      of different liposome forms by choosing HepG2 2.2.15 as an in vitro cell culture
      assay model, and the influence of PEG on the fluidity of liposome membrane with
      the technique of fluorescence polarization were investigated. RESULTS: Cationic
      lipid and different PEGs showed great effects on increasing liposome
      incorporation efficiency (from 0.64% to 86.57%), cellular uptake (from 2.18% to
      48.46%) and fluidity of liposome membrane. The effect of PEG was MW dependent,
      and with the increase of MW, the incorporation efficiency and transfection was
      improved, and the fluidity of liposome membrane increased. CONCLUSION: Addition
      of cationic lipid and high MW PEG into cationic liposomes can enhance the
      cellular delivery and fluidity of cationic liposomes. Also, they can improve the
      incorporation efficiency of cationic liposomes.

PMID- 14730923
TI  - [Evaluation of interaction between drugs and ordered phospholipid membrane by
      immobilized artificial membrane chromatography].
AB  - AIM: To investigate the interaction between drugs and ordered phospholipid
      membrane using immobilized artificial membrane chromatography (IAMC). METHODS:
      IAMC was used to determine the interaction drugs with phospholipid membrane,
      expressed as membrane affinity (lg kIAM). An n-octanol/buffer system was also
      employed as the reference hydrophobicity (lg Do/w,7.4). RESULTS: Within the range
      of used acetonitrile percentages (phi) 0-30% in mobile phase, retention index (lg
      kIAM) showed excellent correlation with phi. Intercepts of fitted straight lines
      between lg kIAM and phi were comparable but slopes were much different for the
      three organic modifiers (acetonitrile, ethanol and methanol). Effects by adding
      CH2 substituent on lipophilicity difference (delta lg kIAM and delta lg Do/w,7.4)
      were similar for p-hydroxyl benzoic methyl ester to butyl ester, whereas
      different for p-hydroxylbenzoic acid to methyl ester. CONCLUSION: IAMC system is
      a convenient, efficient and rapid tool for determining membrane interaction.

PMID- 14730924
TI  - [Studies on diclofenac sodium pulsatile release pellets].
AB  - AIM: To investigate the preparation of diclofenac sodium pulsatile release
      pellets (DS-PRP), the release in vitro and the pharmacokinetics of the drug.
      METHODS: Diclofenac sodium (DS) core pellets prepared by extrusion-spheronization
      technology were coated in a mini-fluidized bed spray coater with swelling
      material as the inner coating swelling layer and ethylcellulose aqueous
      dispersion as the outer coating controlled layer. The effects of formulation and
      medium on pulsatile release of DS were investigated under release rate test.
      Pharmacokinetic and bioavailability study in eight human subjects were performed
      by HPLC method. RESULTS: The delayed-release time and release rate of DS from DS
      PRP were influenced obviously by the swelling material, the concentration of SDS
      in medium, the coating level of the inner swelling layer and the outer controlled
      layer. In vitro, the delayed-release time T0.1 was 3.1 h, and the pulsed-release
      time T0.1-0.2 was 1.2 h. In vivo, the delayed-release time Tlag was 2.8 h, and
      the bioavailability was (91 +/- 12)%. CONCLUSION: The release of drug from DS-PRP
      was shown to be in pulsed way both in vitro and in vivo.

PMID- 14730925
TI  - [Stability studies of sulfated polyguluronic acid ester].
AB  - AIM: To test the stability of marine polysaccharide drug sulfated polyguluronic
      acid ester. METHODS: Four methods including high performance gel chromatography
      (HPGC), poly-acrylamide gel electrophoresis (PAGE), UV scan of absorbance between
      200 and 800 nm and gelatin nephelometry were established. Samples were tested in
      high temperature, high humidity, strong light and accelerated test conditions.
      The methods were used to test the changes of the parameters including molecular
      weight, molecular weight distribution, absorbance between 200 and 800 nm, free
      sulfate, with which we could estimate the stability of sulfated polyguluronic
      acid ester could be estimated. RESULTS: The four methods were suitable to test
      the stability of sulfated polyguluronic acid ester and the sample were stable in
      the conditions as before except in high temperature. CONCLUSION: Sulfated
      polyguluronic acid ester has good stability.

PMID- 14730926
TI  - [Current status of camptothecin derivatives as natural antitumor agents].

PMID- 14730927
TI  - [Analysis and evaluation of the functional state of cardiovascular system in
      cosmonauts during long-term space flights].

PMID- 14730928
TI  - [Compensatory reserves of human organism and population health under conditions
      of exposure to chronic anthropogenic factors and prolonged psychoemotional
      stress].

PMID- 14730929
TI  - [Human physiological responses to hypergravity during orbiting and descent of
      "Soiuz" spacecrafts].

PMID- 14730930
TI  - [Electroencephalographic correlates of mental performance of emotional personal
      and stage situations: Part 2. Characteristics of spatial synchronization].

PMID- 14730931
TI  - [Mechanisms of selective attention during discrimination of concurrent visual and
      auditory verbal information: positron emission tomography and cortical evoked
      potential studies].

PMID- 14730932
TI  - [Hemispheric asymmetry of evoked potentials during performance of visuo-spatial
      tasks].

PMID- 14730933
TI  - [Disorders of emotional memory and ability to identify emotional states in
      patients with Parkinson's disease].

PMID- 14730934
TI  - [Electrophysiological correlates of attentional disorders in adolescents aged 12
      13 years].

PMID- 14730935
TI  - [Systemic organization of perceptive activity in children with different levels
      of mental development].

PMID- 14730937
TI  - [Physiological and psychological characteristics of dependency of the organism on
      the type of personality].

PMID- 14730936
TI  - [Age-related features of the voluntary control of the upright posture].

PMID- 14730938
TI  - [Phenotype characteristics of adolescents aged 14-15 years in Altai].

PMID- 14730939
TI  - [Interrelations between time intervals of kinetocardiogram and pulsogram].

PMID- 14730940
TI  - [Changes in spirometric parameters during local heating of forearm and hand
      skin].

PMID- 14730941
TI  - [Relationships between P300 parameters and the width of lateral ventricles of
      brain in schizophrenic patients and their relatives].

PMID- 14730942
TI  - [Pulmonary heat production in adults after voluntary breath holding].

PMID- 14730943
TI  - [EEG correlates of accuracy of time interval reproduction].

PMID- 14730944
TI  - [Changes in neuromuscular excitability in vibration disease].

PMID- 14730945
TI  - [Our journal is being indexed in Index Medicus: what to do next?].

PMID- 14730946
TI  - [Digital cameras: a practical solution for radiologists (review)].
AB  - Because of the developing technology in computers and internet, the need for
      creating the digital images and transmission of radiographic images over the
      internet is increasing. With their improved quality and decreasing price, digital
      cameras are increasingly attractive for radiologists. In medicine they have
      already found a place in making a decision by allowing transmission of
      radiographic images over the internet and archiving of radiological images for
      personal collections, teaching and publications. When radiographs are digitally
      photographed, the quality of the images can be also protected. The purpose of
      this article is to describe the technical information and inform the radiologists
      about digital cameras, and answer the question 'what kind of digital camera can I
      buy?'.

PMID- 14730947
TI  - [Twinkling artifact in color Doppler ultrasonography: pictorial essay].
AB  - The "twinkling" artifact is a color-flow sonographic artifact presenting as a
      rapidly changing color encoding behind a strongly reflecting structure. Recently,
      "twinkling" artifact has been described behind calcifications in various tissues,
      urinary and gallbladder stones, encrustated indwelling ureteral stents, strongly
      reflecting orbital structures and an intracranial microcoil. It is important to
      recognize this artifact as it could lead to misdiagnosis of vascular flow within
      a tissue. "Twinkling" artifact could be considered as an additional sonographic
      feature in the diagnosis of urinary and bile duct stones and encrustated
      indwelling ureteral stents. "Twinkling" artifact could also play a role in
      detecting the morphology or biochemical composition of urinary stones.

PMID- 14730948
TI  - [Associated brain anomalies and clinical findings in corpus callosum dysgenesis].
AB  - PURPOSE: The aim of this study was to evaluate the relationship between the types
      of the corpus callosum dysgenesis, the associated brain anomalies and clinical
      findings. MATERIALS AND METHODS: We analyzed the MR imaging findings in 169
      patients with callosal dysgenesis. Corpus callosum dysgenesis was categorized
      into agenesis, hypogenesis and hypoplasia. The associated brain anomalies and
      clinical findings were evaluated. RESULTS: Associated brain anomalies were
      observed in 148 patients (87.5%). Twenty-one patients (12.4%) had isolated corpus
      callosum dysgenesis. Dysgenesis included agenesis in 22 (%13), hypogenesis in 46
      (27.2%), and hypoplasia in 101 (59.7%) patients. The clinical findings were most
      commonly observed in patients with hypoplasia. CONCLUSION: The presence of corpus
      callosum dysgenesis is a strong indication of possible associated brain
      anomalies. Corpus callosum dysgenesis and associated brain anomalies should be
      investigated in children with developmental delay, seizures and microcephaly.

PMID- 14730949
TI  - [Flair and diffusion weighted MR imaging in differentiating epidermoid cysts from
      arachnoid cysts].
AB  - PURPOSE: To explore the use of fluid-attenuated inversion recovery (FLAIR) and
      diffusion-weighted echo planar imaging sequences in imaging of the intracranial
      epidermoid and arachnoid cysts and assess the efficiency of those sequences in
      differentiation of epidermoid cysts from arachnoid cysts. MATERIALS AND METHODS:
      This study was performed prospectively by using two different MR devices in 24
      patients (12 epidermoid cysts, 12 arachnoid cysts). T1-weighted spin echo, T2
      weighted fast spin echo, FLAIR and diffusion-weighted echo planar imaging
      sequences were used. Lesions were evaluated qualitatively and quantitatively. In
      qualitative evaluation, the signal intensity of the lesions were compared with
      cerebral spinal flow. Quantitative evaluation was made from the diffusion
      weighted images by measuring values of apparent diffusion coefficient (ADC) from
      the cystic spaces and cerebral white matters. In statistic analyses, Mann-Whitney
      U test was used. RESULTS: Arachnoid cysts had the same intensity with cerebral
      spinal flow in all sequences. Mean ADC value was 3.41 +/- 0.17 x 10(-3) mm2/sn.
      All epidermoid cysts on diffusion-weighted trace images were more hyperintense
      than brain parenchyma. The mean ADC value of the epidermoid cysts was 1.15 +/-
      10(-3) mm2/sn. The ADC values of the epidermoid cysts were lower than the
      arachnoid cysts (p < 0.001), but were higher than the cerebral white matter (p <
      0.01). CONCLUSION: FLAIR sequences were superior to conventional sequences in
      imaging of epidermoid cysts and in differentiation of epidermoid cysts from
      arachnoid cysts. It was also shown that diffusion-weighted trace imaging and
      measurement of ADC values might be used as problem solving tools. Furthermore,
      those sequences may be a guide to demonstrate postoperative residual lesions.

PMID- 14730950
TI  - [Cranial MRI findings in epileptic children].
AB  - PURPOSE: To investigate the cranial MRI findings in childhood epilepsy and to
      detect the most frequent cerebral lesions in epileptic children in our region.
      MATERIALS AND METHODS: In this study, 98 epileptic children were examined with 1
      T MRI equipment between January 1997 and March 2001. T1-weighted sagittal, T2 and
      proton weighted axial and T2-weighted coronal MR images were obtained. Contrast
      enhanced T1-weighted axial, sagittal and coronal MR images were also examined in
      patients with suspicion of infection or intracranial mass. RESULTS: Among a total
      of 98 patients, 65 (66.3%) had no pathological findings on MRI. The pathological
      findings were diffuse cerebral atrophy (18.4%), delay in myelination and
      dismyelination (12.4%), ischemia and infarct (8.2%), arachnoid cysts (6.2%),
      tumoral mass (5.1%), mesial temporal sclerosis (1.0%) and sequelae of kernicterus
      (1.0%). CONCLUSION: MRI has been found to be effective in the evaluation of
      cerebral structures and imaging the pathologies in the etiology of epilepsy and
      other lesions in childhood focal epilepsy. However, MRI does not always appear to
      be successful in detecting the epileptic focus.

PMID- 14730951
TI  - [Comparison of three-dimensional gradient echo, turbo spin echo and steady-state
      gradient echo sequences in axial MRI examination of the cervical spine].
AB  - PURPOSE: The aim of this study was to assess the detectability of the structures
      that are affected by cervical spondylosis by different 3D MRI sequences and
      compare the image quality of those sequences. MATERIALS AND METHODS: Twenty
      healthy volunteers were examined using a 1.5 T MR unit. T2* weighted 3D-gradient
      echo sequence with magnetization transfer saturation pulse (3D-FFE-MTC), T2
      weighted 3D turbo spin echo (TSE) sequence with and without spectral
      presaturation inversion recovery pulse (T2-3D-TSE/SPIR+ and T2-3D-TSE/SPIR-) and
      balanced-FFE (b-FFE) sequences were compared. Spinal cord signal-to-noise ratio
      (SNR), cerebrospinal fluid (CSF) SNR, and CSF-spinal cord contrast-to-noise ratio
      (CNR) were calculated quantitatively. The detectability of neural foramina,
      spinal nerve roots, uncinate process and ligamentum flava were graded on a 5
      point scale (0: minimum, 4: maximum) qualitatively. The presence of the artifacts
      and overall image quality were graded on a 4-point scale (0: minimum, 3:
      maximum). RESULTS: Balanced-FFE sequence yielded the best results for each of
      three quantitative evaluation. In terms of qualitative evaluation, for the
      uncinate process T2-3D-TSE/SPIR- sequence was superior to the other three
      sequences (p < 0.01). For the ligamentum flava T2-3D-TSE/SPIR- and b-FFE
      sequences were superior to the other two (p < 0.01). For the neural foramina b
      FFE yielded the lowest score (3), however the other three sequences were not
      significantly different (3.2-3.5) (p > 0.05). Artifacts were most commonly seen
      using 3D-FFE-MTC. In terms of overall image quality T2-3D-TSE/SPIR- yielded the
      highest score, followed by b-FFE. CONCLUSION: 3D-FFE-MTC sequence is frequently
      preferred for cervical spinal MRI studies. However our study yielded best scores
      for T2-3D-TSE/SPIR, followed by b-FFE in the quantitative and qualitative
      evaluation of the structures affected by cervical spondylosis.

PMID- 14730952
TI  - [Spontaneous regression of basal ganglia lesions in a case of neurofibromatosis
      type 1 (case report)].
AB  - Neurofibromatosis type 1 is characterized on magnetic resonance imaging by optic
      nerve gliomas, parenchymal gliomas, and foci of prolonged T2 relaxation involving
      the brainstem, cerebellum, midbrain, internal capsule, and basal ganglia. We
      report a child with neurofibromatosis type 1 in whom serial magnetic resonance
      imaging demonstrates spontaneous regression of basal ganglia lesions. These
      lesions, characterized on magnetic resonance imaging by increased signal
      intensity on T1- and T2-weighted sequences, involved the globus pallidus and
      internal capsules in a bilateral fashion.

PMID- 14730953
TI  - [Simple and cost effective cannula for sialography: Technical note].
AB  - We developed a simple and cost-effective modified cannula for sialography. The
      cannulae were made from nineteen, twenty-one and twenty-three gauge winged
      infusion set which are generally used for injection of contrast material in
      radiological imaging. In this article, we intend to introduce this cannula and
      discuss its utility.

PMID- 14730954
TI  - [Differential diagnosis of axillary lymph nodes: Usefulness of gray-scale and
      color-power doppler sonography].
AB  - PURPOSE: To evaluate and compare the usefulness of gray-scale and color-power
      Doppler sonography in differentiating benign from malignant axillary lymph nodes,
      and to find out whether the combined usage of both modalities increased the
      diagnostic accuracy. MATERIALS AND METHODS: Sixty lymph nodes in 59 patients were
      evaluated by gray-scale and color-power Doppler sonography. Color-power Doppler
      evaluation was based on the morphological patterns of vascularity. Spectral wave
      form analysis was also performed. Sensitivity, specificity, positive and negative
      predictive values and overall accuracy were calculated for each modality and for
      the combined usage of both modalities. When two modalities were used in
      combination a lymph node was accepted to be 'malignant' if it was diagnosed as
      'malignant' by either or both of the modalities. RESULTS: Forty lymph nodes were
      confirmed to be malignant and 20 were benign by histopathologic or sytologic
      examination or by clinical and sonographic follow-up. Gray-scale and color-power
      sonography had sensitivities of 92%, 89%; specificities of 70%, 75%; positive
      predictive values of 86%, 87%; negative predictive values of 82%, 79%; and
      overall accuracies of 85%, 85% respectively. The combined usage of both
      modalities yielded a sensitivity of 98%, specificity of 70%, positive predictive
      value of 87%, negative predictive value of 88%, and an overall accuracy of 88%.
      CONCLUSION: Gray-scale sonography and color-power Doppler examination have the
      same overall accuracy for the differentiation of benign from malignant axillary
      lymph nodes. Spectral wave form analysis was proved to be statistically
      insignificant. The combined usage of both modalities would decrease the number of
      false negative cases.

PMID- 14730955
TI  - [Cross-sectional imaging findings in intradiverticular bladder tumors: Case
      report].
AB  - Neoplasms originating in bladder diverticula are characterized by early
      transmural invasion and a tendency for higher histopathological grades, which
      make prompt diagnosis and treatment crucial in these tumors. Filling defects
      caused by intradiverticular tumors cannot always be visualized in intravenous
      urography and/or cystography. Cross-sectional imaging methods including
      ultrasonography, computed tomography and magnetic resonance imaging have been
      used singly or in combination in neoplasms of the lower urinary tract. We herein
      present radiological findings in four patients with intradiverticular bladder
      neoplasms. Although diverticula were readily visualized in all patients,
      intravenous urography did not detect the neoplasm in two patients. Accurate
      diagnosis and staging were possible in all patients with both ultrasonography and
      computed tomography. In one patient magnetic resonance imaging clearly showed the
      intradiverticular tumor and peridiverticular extension. Cross-sectional imaging
      methods should be used in the evaluation of bladder diverticula as an adjunct to
      intravenous urography.

PMID- 14730956
TI  - [Celiac ganglion blockade: the effectiveness of CT guided percutaneous anterior
      approach].
AB  - PURPOSE: To investigate the effectiveness and safety of celiac ganglion blockade
      in cases with abdominal malignancies who are narcotic analgesic dependent for
      control of severe abdominal pain. MATERIALS AND METHODS: A total of 30 celiac
      ganglion blockades were performed in 27 patients between the ages of 19 and 75. A
      22 G Chiba needle was placed through the percutaneous anterior approach into the
      celiac ganglion region under the guidance of CT, and 98% alcohol was
      administered. The procedure was repeated in three cases due to insufficient
      response. RESULTS: In 24 (88.8%) of the 27 cases, the severity of pain decreased.
      Total relief of the pain was achieved in 13 (48.1%) cases. In 9 (33.3%) cases
      pain was controlled with non-narcotic analgesics. In 2 (7.4%) cases, the dose of
      the narcotic analgesic decreased. There was no change in the severity of the pain
      in 3 (11.1%) cases. Transient complications were diarrhea in 4 (14.8%),
      hypotension in 6 (22.2%) cases and hemiparesis in one (3.7%) case. CONCLUSION:
      Celiac ganglion blockade through the percutaneous anterior approach under the
      guidance of CT should be preferred for the control of pain in the early periods
      in cases with abdominal malignancies, especially gastric and pancreatic, due to
      easy performance, safety, lower incidence of complications, high success rate and
      low cost.

PMID- 14730957
TI  - [Stent originating pseudoaneurysm: endovascular treatment of a rare complication
      with hemobahn-covered stent (case report)].
AB  - Delayed rupture and aneurysm formation at the site of stent placement has rarely
      been described in the literature. However, these rare complications are usually
      fatal and the patients are taken to the operating theater for repeat endovascular
      treatment. In this case report, a rare complication that developed after
      percutaneous recanalization and stent angioplasty of chronic long-segment iliac
      artery occlusion, and the treatment of this complication are presented.

PMID- 14730958
TI  - [Relationship of coronary artery calcification identified by electron beam
      tomography with age and gender].
AB  - PURPOSE: To investigate the relationship of coronary artery calcification
      identified by electron beam tomography with age and gender. MATERIALS AND
      METHODS: Electron beam tomography was performed in 654 patients to detect
      coronary artery calcification. Examinations were done with electron beam
      tomography (Imatron C-150 XP), using prospective electrocardiography triggering
      to prevent cardiac motion artifacts. Total calcification scores were calculated
      based on the number, area and computed tomographic number of the calcifications.
      The influence of age and gender on the presence and amount of coronary artery
      calcification were evaluated. RESULTS: There were significant differences (p <
      0.001) in mean total calcification scores between men and women. Men always had
      more coronary artery calcification than women at all age groups. The youngest
      patient with coronary artery calcification was below 40 years of age in men and
      above 40 years of age in women. The difference in the prevalence of coronary
      artery calcification between men and women was great at younger ages, and
      decreased after age 60. The difference in prevalence of coronary artery
      calcification for men and women was starting to be decreased after age 60.
      CONCLUSION: We observed that coronary artery calcification, a marker of
      arteriosclerosis, is strongly associated with age and gender.

PMID- 14730959
TI  - [Venous reflux: Measurement variability due to positional differences].
AB  - PURPOSE: The purpose of this study was to evaluate the role of the subject's
      position and two different maneuvers in the reflux measurements in femoral veins.
      MATERIALS AND METHODS: Venous reflux times in the common femoral vein (CFV) and
      superficial femoral vein (SFV) were studied in 50 healthy subjects (25 women, 25
      male) aged between 22-57 years-old while the subjects were in supine and standing
      positions. Reflux was provocated only by Valsalva maneuver (VM) when the subject
      was lying down, whereas it was provocated by (1) Valsalva maneuver and (2)
      compression and release maneuver, respectively, when the subject was standing.
      Reflux times were recorded with each of the three methods. RESULTS: Regarding
      CFV, a reflux time of 1 second or more was recorded in 29 limbs (29%) only in the
      supine position. Of these 29 measurements, 19 were between 1 and 1.9 sec and 8
      between 2 and 2.9 sec. When the subjects were examined in the standing position,
      the prevalence of reflux lasting more than 1 sec substantially decreased (5%).
      The prevalence of reflux lasting less than 0.5 sec was 97% with standing
      compression maneuver, 84% with standing VM and 27% with supine VM. Similarly,
      prevalence of reflux of longer than 0.5 sec or 1 sec was lower in the standing
      position than in the supine position in SFV. In CFV, mean reflux time was 1.3 sec
      in the supine position, whereas it was 0.7 sec and 0.4 sec with standing
      compression and standing Valsalva maneuvers, respectively. Corresponding values
      in SFV were 0.5 sec, 0.3 sec and 0.2 sec, respectively. CONCLUSION: The
      probability of making a false positive diagnosis of pathological reflux is high
      with supine examinations. When an examination in the supine position reveals a
      reflux time of longer than 1 second, making the patient stand up is expected to
      yield more reliable results. Compression and release maneuver, with its lowest
      false positive reflux prevalence, is the most reliable method in the evaluation
      of venous insufficiency.

PMID- 14730960
TI  - [Pancreaticopleural fistula: CT, MRI and clinical findings].

PMID- 14730961
TI  - [Pelvic digit: often by chance the same growth anomaly].

PMID- 14730962
TI  - EX1 hydrogen exchange and protein folding.
AB  - Slow amide hydrogen exchange is an increasingly popular tool for investigating
      structure and function in proteins. The kinetic model for slow hydrogen exchange
      has two limits, called EX2 and EX1, wherein the thermodynamics and kinetics of
      protein motions, respectively, are reported by the exchange data. While many
      laboratories have demonstrated that EX2 exchange can indeed provide accurate
      results regarding the thermodynamics of protein stability, the potential of EX1
      exchange to follow the kinetics of protein unfolding and folding is only
      beginning to be realized. EX1 hydrogen exchange has advantages over more
      traditional folding experiments: it provides single-residue resolution, as well
      as whole-molecule information, the latter of which can be interpreted in terms of
      the cooperativity of unfolding. However, key questions remain regarding the
      interpretation of EX1 hydrogen exchange.

PMID- 14730963
TI  - Variant surface glycoprotein from Trypanosoma evansi is partially responsible for
      the cross-reaction between Trypanosoma evansi and Trypanosoma vivax.
AB  - Salivarian trypanosomes use antigenic variation of their variant-specific surface
      glycoprotein (VSG) coat as a defense against the host immune system. Although
      about 1000 VSG and pseudo-VSG genes are scattered throughout the trypanosome
      genome, each trypanosome expresses only one VSG, while the rest of the genes are
      transcriptionally silent. A 64-kDa glycosylated cross-reacting antigen between
      Trypanosoma evansi and Trypanosoma vivax (p64), which was purified from the TEVA1
      T. evansi Venezuelan isolate, was proven here to represent the soluble form of a
      VSG. Initially, a biochemical characterization of p64 was carried out. Gel
      filtration chromatography, sedimentation, and chemical cross-linking provided
      evidences of the dimeric nature of p64. The hydrodynamic parameters indicated
      that p64 is asymmetrical with a frictional ratio f/fo = 1.57. Isoelectric
      focusing and two-dimensional polyacrylamide gel electrophoresis revealed that p64
      contained two isoforms with isoelectric points of 6.8-6.9 and 7.1-7.2. When p64
      and three p64 Staphylococcus aureus V8 proteolytic fragments were sequenced, the
      same N-termini sequence was obtained: Ala-Pro-Ile-Thr-Asp-Ala-Asp-Leu-Gly-Pro-Ala
      Gln-Ile-Ala-Asp, which displayed a significant homology with a putative
      Trypanosoma brucei VSG gene located on chromosome 4. Additionally,
      immunofluorescence microscopy on T. evansi and T. vivax established that p64 and
      its T. vivax homologue were confined to the surface of both parasites. An
      immunological characterization of this antigen was also carried out using several
      Venezuelan T. evansi isolates expressing different VSGs, which were obtained from
      naturally infected animals. Although sera from animals infected with the various
      T. evansi isolates recognized p64, only one isolate, besides TEVA1, contained
      polypeptides that were recognized by anti-p64 antibodies. All these results
      together with prior evidences [Uzcanga, G. et al. (2002) Parasitology 124, 287
      299] confirmed that p64 is the soluble form of a T. evansi VSG, containing common
      epitopes recognized by sera from animals infected with T. evansi or T. vivax.
      Despite the huge repertoire of VSG genes existing on bloodstream trypanosomes,
      our data also demonstrated the potential use of a VSG variant from the TEVA1 T.
      evansi isolate as a diagnostic reagent.

PMID- 14730964
TI  - Successful design and synthesis of a polarity-triggered beta-->alpha
      conformational switch using the side chain interaction index (SCII) as a measure
      of local structural stability.
AB  - Certain sequences within proteins have the ability to undergo an abrupt
      cooperative conformational switch from beta-strand to helix in response to
      decreasing polarity of the environment. This behavior was first observed at the
      CD4 binding site of the envelope glycoprotein gp120 of HIV-1, but evidence has
      accumulated that polarity-driven beta --> alpha switches may be widespread,
      serving both to facilitate binding on protein/membrane or protein/protein contact
      and to signal that docking has occurred. The characteristics identified so far
      that distinguish switch sequences (a reverse turn at the N-terminus that acts as
      a helix initiation site, a conserved tryptophan residue downstream, and high
      potential for both the helix and beta-fold) appear to be necessary but not
      sufficient, as some otherwise promising sequences found in data bank searches
      proved not to be capable of cooperative refolding. Analysis of existing switches
      has led to the development of the side chain interaction index (SCII) as a
      further parameter characterizing the beta --> alpha polarity-driven switch. Data
      bank searches using this additional parameter have successfully identified a
      series of new potential switch sequences. All of them have in common the amino
      acid tetrad LPCR at the N-terminus and a tryptophan 5-20 residues C-terminal to
      it. Those with a high SCII as well, when synthesized and tested, exhibited
      strongly cooperative polarity-driven refolding. Control peptides, containing all
      other parameters but with a low SCII, did not. Using this new information, an
      artificial sequence was designed that had a high SCII as well as the initiation
      site, conserved tryptophan, and high Palpha and Pbeta. When synthesized and
      tested, this sequence did in fact behave as a conformational switch, refolding
      cooperatively from beta-fold to helix at a threshold value of 30% TFE. The
      successful design of a polarity-driven conformational switch opens the
      possibility of using this motif as a tool in protein engineering.

PMID- 14730965
TI  - Tripeptides with ionizable side chains adopt a perturbed polyproline II structure
      in water.
AB  - The present paper reports the conformations of the acidic and basic
      homotripeptides triglutamate, triaspartate, and trilysine in aqueous solution to
      better understand their relevance for the structure of disordered proteins and
      protein segments and for a variety of protein binding processes. The
      determination of the dihedral angles of the central amino acid residue was
      achieved by analyzing the amide I band profile of the respective polarized
      visible Raman, Fourier transform infrared (FT-IR), and vibrational circular
      dichroism (VCD) spectra by means of recently developed algorithms [Schweitzer
      Stenner, R. (2002) Biophys. J. 83, 523-532; Eker et al. (2002) J. Am. Chem. Soc.
      124, 523-532]. The results were validated by measuring the UV electronic circular
      dichroism (ECD) spectra of the peptides. The analyses revealed that a polyproline
      II-like conformation is predominant at room temperature. For triaspartate and
      triglutamate the dihedral angles of phi = -70 degrees, psi = 165 degrees and phi
      = -60 degrees, psi = 160 degrees were obtained, respectively. A similar
      conformation, i.e., phi = -50 degrees, psi = 170 degrees, was obtained for
      trilysine, which is at variance with the earlier reported left-handed turn
      structure. The ECD spectrum of charged tripeptides displayed symmetric negative
      and positive couplets at 190 and 210 nm, which are interpreted as indicating a
      somewhat, perturbed polyproline II conformation, in agreement with the obtained
      dihedral angles. Comparison with literature data shows that the investigated
      tripeptides are ideal model systems for understanding the local conformation of
      functionally relevant K3, K2X, E3, and D3 segments in a variety of different
      proteins.

PMID- 14730966
TI  - Crystal structure of a human VH: requirements for maintaining a monomeric
      fragment.
AB  - The variable domain of dromedary immunoglobulins comprises only the heavy chain
      and is missing the light-chain variable domain. This single domain is sufficient
      for antigen recognition and binding-half that required by other mammals. Human
      antibody-VHs have previously been camelized to be soluble stable fragments that
      retain antigen binding. Such engineered VHH are of interest in drug development,
      since they are nonimmunogenic, and in other biotechnology applications. We
      present the structure of a camelized human antibody fragment (cVH), which is a
      competitive and reversible inhibitor of the NS3 serine protease of the hepatitis
      C virus (HCV). In solution, this cVH undergoes a concentration-dependent monomer
      dimer equilibrium. The structure confirms the minimum mutational requirements of
      the VL-binding face. The fragment also suggests a means by which the observed
      dimerization occurs, highlighting the importance of the composition of the CDR3
      in maintaining a truly camelized VH.

PMID- 14730967
TI  - The crystal structure of fibroblast growth factor (FGF) 19 reveals novel features
      of the FGF family and offers a structural basis for its unusual receptor
      affinity.
AB  - The 22 members of the FGF family have been implicated in cell proliferation,
      differentiation, survival, and migration. They are required for both development
      and maintenance of vertebrates, demonstrating an exquisite pattern of affinities
      for both protein and proteoglycan receptors. FGF19, one of the most divergent
      human FGFs, is unique in binding solely to one receptor, FGFR4. We have used
      molecular replacement to solve the crystal structure of FGF19 at 1.3 A resolution
      using five superimposed FGF structures as the search model. The structure shows
      that two novel disulfide bonds found in FGF19, one of which appears to be
      conserved among several of the other FGFs, stabilize extended loops. The key
      heparin-binding loops of FGF19 have radically different conformations and charge
      patterns, compared to other FGFs, correlating with the unusually low affinity of
      FGF19 for heparin. A model for the complex of FGF19 with FGFR4 demonstrates that
      unique sequences in both FGF19 and FGFR4 are key to the formation of the complex.
      The structure therefore offers a clear explanation for the unusual affinity of
      FGF19 for FGFR4 alone.

PMID- 14730968
TI  - Stereochemical control of small molecule binding to bulged DNA: comparison of
      structures of spirocyclic enantiomer-bulged DNA complexes.
AB  - The solution structure of the complex formed between an oligonucleotide
      containing a two-base bulge (5'-CACGCAGTTCGGAC.5'-GTCCGATGCGTG) and ent-DDI, a
      designed synthetic agent, has been elucidated using high-resolution NMR
      spectroscopy and restrained molecular dynamic simulation. Ent-DDI is a left
      handed wedge-shaped spirocyclic molecule whose aglycone portion is an enantiomer
      of DDI, which mimics the spirocyclic geometry of the natural product, NCSi-gb,
      formed by base-catalyzed activation of the enediyne antibiotic neocarzinostatin.
      The benzindanone moiety of ent-DDI intercalates between the A6.T21 and the T9.A20
      base pairs, overlapping with portions of the purine bases; the
      dihydronaphthalenone moiety is positioned in the minor groove along the G7-T8-T9
      bulge sequence; and the aminoglycoside is in the middle of the minor groove,
      approaching A20 of the nonbulged strand. This alignment of ent-DDI along the DNA
      helical duplex is in the reverse direction to that of DDI. The aminoglycoside
      moiety of ent-DDI is positioned in the 3' direction from the bulge region,
      whereas that of the DDI is positioned in the 5' direction from the same site.
      This reverse binding orientation within the bulge site is the natural consequence
      of the opposite handedness imposed by the spirocyclic ring junction and permits
      the aromatic ring systems of the two spirocyclic enantiomers access to the bulge
      region. NMR and CD data indicate that the DNA in the DDI-bulged DNA complex
      undergoes a larger conformational change upon complex formation in comparison to
      the ent-DDI-bulged DNA, explaining the different binding affinities of the two
      drugs to the bulged DNA. In addition, there are different placements of the bulge
      bases in the helical duplex in the two complexes. One bulge base (G7) stacks
      inside the helix, and the other one (T8) is extrahelical in the DDI-bulged DNA
      complex, whereas both bulge bases in the ent-DDI-bulged DNA complex prefer
      extrahelical positions for drug binding. Elucidation of the detailed binding
      characteristics of the synthetic spirocyclic enantiomers provides a rational
      basis for the design of stereochemically controlled drugs for bulge binding
      sites.

PMID- 14730969
TI  - A residue in MutY important for catalysis identified by photocross-linking and
      mass spectrometry.
AB  - MutY is an adenine glycosylase in the base excision repair (BER) superfamily that
      is involved in the repair of 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG):A and G:A
      mispairs in DNA. MutY contains a [4Fe-4S]2+ cluster that is part of a novel DNA
      binding motif, referred to as the iron-sulfur cluster loop (FCL) motif. This
      motif is found in a subset of members of the BER glycosylase superfamily,
      defining the endonuclease III-like subfamily. Site-specific cross-linking was
      successfully employed to investigate the DNA-protein interface of MutY. The
      photoreactive nucleotide 4-thiothymidine (4ST) incorporated adjacent to the OG:A
      mismatch formed a specific cross-link between the substrate DNA and MutY. The
      amino acid participating in the cross-linking reaction was characterized by
      positive ion electrospray ionization (ESI) tandem mass spectrometry. This
      analysis revealed Arg 143 as the site of modification in MutY. Arg 143 and nearby
      Arg 147 are conserved throughout the endo III-like subfamily. Replacement of Arg
      143 and Arg 147 with alanine by site-directed mutagenesis reduces adenine
      glycosylase activity of MutY toward OG:A and G:A mispairs. In addition, the R143A
      and R147A enzymes exhibit a reduced affinity for duplexes containing the
      substrate analogue 2'-deoxy-2'-fluoroadenosine opposite OG and G. Modeling of
      MutY bound to DNA using an endonuclease III-DNA complex structure shows that
      these two conserved arginines are located within close proximity to the DNA
      backbone. The insight from mass spectrometry experiments combined with functional
      mutagenesis results indicate that these two amino acids in the [4Fe-4S]2+ cluster
      containing subfamily play an important role in recognition of the damaged DNA
      substrate.

PMID- 14730970
TI  - Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase
      and evidence for the proposed benzene oxide intermediate in homogentisate
      formation.
AB  - p-Hydroxyphenylpyruvate dioxygenase (HPD) plays a key role in the normal
      catabolism of tyrosine. An Fe2+/oxygen-dependent enzyme, it converts p
      hydroxyphenylpyruvate into homogentisate and is part of the superfamily of alpha
      ketoglutarate-dependent enzymes that couples oxidative decarboxylation of an
      alpha-ketoacid cofactor to oxidative modification of its substrate. In this case,
      the alpha-ketoacid is part of the substrate side chain. HPD shows strong homology
      to p-hydroxymandelate synthase (HMS), an enzyme that catalyzes the formation of p
      hydroxymandelate from p-hydroxyphenylpyruvate, an early step in the biosynthesis
      of p-hydroxyphenylglycine, which is a nonproteinogenic amino acid incorporated
      into several biologically active secondary metabolites. Sequence alignment
      between the HPD and the HMS enzyme families and analysis of the Pseudomonas
      fluorescens HPD crystal structure highlighted four residues within each active
      site that may play roles in catalytic differentiation between the two products.
      We attempted to convert Streptomyces avermitilis HPD into an engineered S.
      avermitilis HMS by site-directed mutagenesis of these four residues individually
      and in combination. HPLC assay analysis of each His6-tagged mutant indicated that
      F337I successfully produced p-hydroxymandelate, along with homogentisate and an
      unknown compound. The structure of the latter was determined to be an oxepinone
      derived from the benzene-oxide intermediate long hypothesized in HPD catalysis.

PMID- 14730971
TI  - Roles of N-terminal region residues Lys11, Arg13, and Arg24 of antithrombin in
      heparin recognition and in promotion and stabilization of the heparin-induced
      conformational change.
AB  - The N-terminal region residues, Lys11, Arg13, and Arg24, of the plasma
      coagulation inhibitor, antithrombin, have been implicated in binding of the
      anticoagulant polysaccharide, heparin, from the identification of natural mutants
      with impaired heparin binding or by the X-ray structure of a complex of the
      inhibitor with a high-affinity heparin pentasaccharide. Mutations of Lys11 or
      Arg24 to Ala in this work each reduced the affinity for the pentasaccharide
      approximately 40-fold, whereas mutation of Arg13 to Ala led to a decrease of only
      approximately 7-fold. All three substitutions resulted in the loss of one ionic
      interaction with the pentasaccharide and those of Lys11 or Arg24 also in 3-5-fold
      losses in affinity of nonionic interactions. Only the mutation of Lys11 affected
      the initial, weak interaction step of pentasaccharide binding, decreasing the
      affinity of this step approximately 2-fold. The mutations of Lys11 and Arg13
      moderately, 2-7-fold, altered both rate constants of the second, conformational
      change step, whereas the substitution of Arg24 appreciably, approximately 25
      fold, reduced the reverse rate constant of this step. The N-terminal region of
      antithrombin is thus critical for high-affinity heparin binding, Lys11 and Arg24
      being responsible for maintaining appreciable and comparable binding energy,
      whereas Arg13 is less important. Lys11 is the only one of the three residues that
      is involved in the initial recognition step, whereas all three residues
      participate in the conformational change step. Lys11 and Arg13 presumably bind
      directly to the heparin pentasaccharide by ionic, and in the case of Lys11, also
      nonionic interactions. However, the role of Arg24 most likely is indirect, to
      stabilize the heparin-induced P-helix by interacting intramolecularly with Glu113
      and Asp117, thereby positioning the crucial Lys114 residue for optimal ionic and
      nonionic interactions with the pentasaccharide. Together, these findings show
      that N-terminal residues of antithrombin make markedly different contributions to
      the energetics and dynamics of binding of the pentasaccharide ligand to the
      native and activated conformational states of the inhibitor that could not have
      been predicted from the X-ray structure.

PMID- 14730972
TI  - Effects of backbone contacts 3' to the abasic site on the cleavage and the
      product binding by human apurinic/apyrimidinic endonuclease (APE1).
AB  - The mammalian apurinic/apyrimidinic (AP) endonuclease (APE1) is a multifunctional
      protein that plays essential roles in DNA repair and gene regulation. We
      decomposed the APEs into 12 blocks of highly conserved sequence and structure
      (molegos). This analysis suggested that residues in molegos common to all APEs,
      but not to the less specific nuclease, DNase I, would dictate enhanced binding to
      damaged DNA. To test this hypothesis, alanine was substituted for N226 and N229,
      which form hydrogen bonds to the DNA backbone 3' of the AP sites in crystal
      structures of the APE1/DNA complex. While the cleavage rate at AP sites of both
      N226A and N229A mutants increased, their ability to bind to damaged DNA
      decreased. The ability of a double mutant (N226A/N229A) to bind damaged DNA was
      further decreased, while the V(max) was almost identical to that of the wild-type
      APE1. A double mutant at N226 and R177, a residue that binds to the same
      phosphate as N229, had a significantly decreased activity and substrate binding.
      As the affinity for product DNA was decreased in all the mutants, the enhanced
      reaction rate of the single mutants could be due to alleviation of product
      inhibition of the enzyme. We conclude that hydrogen bonds to phosphate groups 3'
      to the cleavage site is essential for APE1's binding to the product DNA, which
      may be necessary for efficient functioning of the base excision repair pathway.
      The results indicate that the molego analysis can aid in the redesign of proteins
      with altered binding affinity and activity.

PMID- 14730973
TI  - Toward parathyroid hormone minimization: conformational studies of cyclic PTH(1
      14) analogues.
AB  - The N-terminal fragment of PTH(1-34) is critical for PTH1 receptor activation.
      Various modifications of PTH(1-14) have been shown to result in a considerable
      increase in signaling potency [Shimizu et al. (2000) J. Biol. Chem. 275, 21836
      21843]. Our structural investigations revealed an unusually stable helical
      structure of the signaling domain (1-14), where residues 6 (Gln) and 10 (Gln or
      Asn) were located on the same face of the alpha-helix. To test whether a stable N
      terminal alpha-helix is required for productive interaction with PTH1 receptor,
      we designed two conformationally restricted PTH(1-14) analogues, each containing
      a lactam bridge at positions 6 and 10. Specifically, substitutions Gln(6)-
      >Glu(6) and Asn(10)-->Lys(10) were introduced into the most potent
      [Ala(1,3,12),Gln(10),Har(11),Trp(14)]PTH(1-14)NH2 agonist. Both the Glu(6)
      Lys(10) and Lys(6)-Glu(10) lactam-bridged analogues were characterized to examine
      the importance of orientation of the lactam. According to biological studies
      [Shimizu et al. (2003) Biochemistry 42, 2282-2290], none of the 6/10 substituted
      analogues (linear or cyclic) remained as active as the parent peptide. However,
      relative to their corresponding linear peptides, lactam-bridged analogues either
      maintained potency or showed 6-fold improvement. High-resolution structures as
      determined by 1H NMR and NOE-restrained molecular dynamics simulations clearly
      illustrate the structural differences between the linear and cyclic PTH(1-14)
      fragments, supporting the hypothesis that an alpha-helix is the preferred
      bioactive conformation of the N-terminal fragment of PTH. In addition, our
      results demonstrate that the structural order of the very first residues (1-4) of
      the signaling domain plays a significant role in PTH action.

PMID- 14730974
TI  - Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human
      versus mouse Ah receptor complexes.
AB  - The aryl hydrocarbon receptor (AhR) mediates the toxicologic and carcinogenic
      properties of 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the cytoplasm, the AhR is
      complexed with a dimer of hsp90, and the hepatitis B virus X-associated protein 2
      (XAP2). Most studies that have examined the ability of XAP2 to modulate the AhR
      have characterized the mouse receptor (mAhR). However, the amino acid sequence of
      mAhR is significantly different from human AhR (hAhR) in the carboxy terminal
      half of the protein, and this could lead to differences in the behavior of the
      two receptors. mAhR-yellow fluorescent protein (YFP) and hAhR-YFP were used to
      compare nucleocytoplasmic shuttling properties and the ability of XAP2 to
      modulate their activity. As reported previously, mAhR localized predominantly in
      the nucleus and was redistributed to the cytoplasm by coexpression of XAP2 in COS
      1 cells. Leptomycin B treatment revealed that XAP2 blocked mAhR-YFP translocation
      to the nucleus in the absence of ligand. In contrast, hAhR-YFP localized
      predominantly in the cytoplasm, and coexpression of XAP2 did not affect this
      localization, and did not block nuclear accumulation in the presence of
      leptomycin B. An XAP2 fusion protein with a nuclear localization signal fused to
      the carboxy terminus (XAP2-NLS) was utilized to test whether this protein could
      drag the AhR into the nucleus. Coexpression of mAhR-YFP and XAP2-NLS caused
      cytoplasmic localization of the mAhR, while hAhR-YFP was partially localized in
      the nucleus, suggesting that XAP2 remains bound to the hAhR during
      nucleocytoplasmic shuttling. The presence of XAP2 in the ligand-bound hAhR
      complex enhanced the rate of nuclear translocation but repressed transcriptional
      activity. Together, these results suggest that the hAhR differs biochemically
      from the mAhR.

PMID- 14730975
TI  - Mechanistic and kinetic study of the ATP-dependent DNA ligase of Neisseria
      meningitidis.
AB  - The gene from Neisseria meningitidis serogroup A, encoding a putative, secreted
      ATP-dependent DNA ligase was cloned and overexpressed, and the soluble protein
      was purified. Mass spectrometry indicated that the homogeneous protein was
      adenylated as isolated, and sedimentation velocity experiments suggested that the
      enzyme exists as a monomer in solution. The 31.5 kDa protein can catalyze the ATP
      dependent ligation of a singly nicked DNA duplex but not blunt-end joining. The
      first step of the overall reaction, the ATP-dependent formation of an adenylated
      ligase, was studied by measuring the formation of the covalent intermediate and
      isotope exchange between [alpha-32P] ATP and PPi. Mg2+ was absolutely required
      for this reaction and was the best divalent cation to promote catalysis.
      Electrophoretic gel mobility shift assays revealed that the enzyme bound both
      unnicked and singly nicked double stranded DNA with equivalent affinity (Kd
      approximately 50 nM) but cannot bind single stranded DNA. Preadenylated DNA was
      synthesized by transferring the AMP group from the enzyme to the 5'-phosphate of
      a 3'-dideoxy nicked DNA. The rate of phosphodiester bond formation at the
      preadenylated nick was also Mg(2+)-dependent. Kinetic data showed that the
      overall rate of ligation, which occurred at 0.008 s(-1), is the result of three
      chemical steps with similar rate constants (approximately 0.025 s(-1)). The Km
      values for ATP and DNA substrates, in the overall ligation reaction, were 0.4
      microM and 30 nM, respectively.

PMID- 14730976
TI  - Monomeric and dimeric bZIP transcription factor GCN4 bind at the same rate to
      their target DNA site.
AB  - Basic leucine zipper (bZIP) transcription factors are dimeric proteins that
      recognize dyadic and mostly palindromic DNA sites. Dimerization of bZIP
      transcription factor GCN4 is linked to the folding of its C-terminal leucine
      zipper domain. However, monomeric GCN4, lacking a folded leucine zipper, also
      recognizes the DNA site with dimerization taking place on the DNA. Here we report
      the kinetics of DNA recognition by unfolded monomeric and folded dimeric
      derivatives of GCN4 using a 19 bp double-stranded DNA containing a palindromic
      CRE site. The rate of DNA binding of both monomeric and dimeric GCN4 has a
      bimolecular rate constant of 3-5 x 10(8) M(-1) s(-1), which is near the diffusion
      limit. Because the rate of dimerization of GCN4 is slower (1.7 x 10(7) M(-1) s(
      1)) than the rate of DNA association, the formation of the dimeric GCN4-DNA
      complex through consecutive binding of two monomers (monomer pathway) is faster
      when starting from free monomers. Thus, the results presented here support
      facilitated and rapid target recognition by the monomeric transcription factor.
      However, DNA binding of preformed folded dimeric GCN4 is as rapid as complex
      formation through the monomer pathway. Therefore, the monomer and dimer pathways
      are kinetically equivalent if monomeric and dimeric GCN4 are at equilibrium.
      Hence, the dimer pathway may also have a role under in vivo conditions. The lower
      affinity of GCN4 in which two DNA contacting residues have been mutated is due
      exclusively to the faster dissociation of the mutant protein-DNA complex and not
      to slower complex formation.

PMID- 14730977
TI  - Cobalt enhances DNA cleavage mediated by human topoisomerase II alpha in vitro
      and in cultured cells.
AB  - Although cobalt is an essential trace element for humans, the metal is genotoxic
      and mutagenic at higher concentrations. Treatment of cells with cobalt generates
      DNA strand breaks and covalent protein-DNA complexes. However, the basis for
      these effects is not well understood. Since the toxic events induced by cobalt
      resemble those of topoisomerase II poisons, the effect of the metal on human
      topoisomerase IIalpha was examined. The level of enzyme-mediated DNA scission
      increased 6-13-fold when cobalt(II) replaced magnesium(II) in cleavage reactions.
      Cobalt(II) stimulated cleavage at all DNA sites observed in the presence of
      magnesium(II), and the enzyme cut DNA at several "cobalt-specific" sites. The
      increased level of DNA cleavage in the presence of cobalt(II) was partially due
      to a decrease in the rate of enzyme-mediated religation. Topoisomerase IIalpha
      retained many of its catalytic properties in reactions that included cobalt(II),
      including sensitivity to the anticancer drug etoposide and the ability to relax
      and decatenate DNA. Finally, cobalt(II) stimulated topoisomerase IIalpha-mediated
      DNA cleavage in the presence of magnesium(II) in purified systems and in human
      MCF-7 cells. These findings demonstrate that cobalt(II) is a topoisomerase II
      poison in vitro and in cultured cells and suggest that at least some of the
      genotoxic effects of the metal are mediated through topoisomerase IIalpha.

PMID- 14730978
TI  - Histone-DNA binding free energy cannot be measured in dilution-driven
      dissociation experiments.
AB  - Despite decades of study on nucleosomes, there has been no experimental
      determination of the free energy of association between histones and DNA.
      Instead, only the relative free energy of association of the histone octamer for
      differing DNA sequences has been available. Recently, a method was developed
      based on quantitative analysis of nucleosome dissociation in dilution experiments
      that provides a simple practical measure of nucleosome stability. Solution
      conditions were found in which nucleosome dissociation driven by dilution fit
      well to a simple model involving a noncooperative nucleosome assembly/disassembly
      equilibrium, suggesting that this approach might allow absolute equilibrium
      affinity of the histone octamer for DNA to be measured. Here, we show that the
      nucleosome assembly/disassembly process is not strictly reversible in these
      solution conditions, implying that equilibrium affinities cannot be obtained from
      these measurements. Increases in [NaCl] or temperature, commonly employed to
      suppress kinetic bottlenecks in nucleosome assembly, lead to cooperative behavior
      that cannot be interpreted with the simple assembly/disassembly equilibrium
      model. We conclude that the dilution experiments provide useful measures of
      kinetic but not equilibrium stability. Kinetic stability is of practical
      importance: it may govern nucleosome function in vivo, and it may (but need not)
      parallel absolute thermodynamic stability.

PMID- 14730979
TI  - Role of protein conformational mobility in enzyme catalysis: acylation of alpha
      chymotrypsin by specific peptide substrates.
AB  - To probe the mechanistic origins of convex Eyring plots that have been observed
      for alpha-chymotrypsin (alpha-CT)-catalyzed hydrolysis of specific p-nitroanilide
      substrates [Case, A., and Stein, R. L. (2003) Biochemistry 42, 3335-3348], we
      determined the temperature-dependence of (15)N-kinetic isotope effects for the
      alpha-CT-catalyzed hydrolysis of N-succinyl-Phe p-nitroanilide (Suc-Phe-pNA). To
      provide an interpretational context for these enzymatic isotope effects, we also
      determined 15N-KIE for alkaline hydrolysis of p-nitroacetanilide. In 0.002 and 2
      N hydroxide (30 degrees C), 15N-KIE values are 1.035 and 0.995 (+/-0.001),
      respectively, and are consistent with the reported [HO-]-dependent change in rate
      limiting step from leaving group departure from an anionic tetrahedral
      intermediate in dilute base, to hydroxide attack in concentrated base. For the
      alpha-CT-catalyzed hydrolysis of Suc-Phe-pNA, 15N-KIE is on kc/Km and thus
      reflects structural features of transition states for all reaction steps up to
      and including acylation of the active site serine. The isotope effect at 35
      degrees C is 1.014 (+/-0.001) and suggests that in the transition state for this
      reaction, departure of leaving group from the tetrahedral intermediate is well
      advanced. Significantly, 15N-KIE does not vary over the temperature range 5-45
      degrees C. This result eliminates one of the competing hypotheses for the convex
      Eyring plot observed for this reaction, that is, a temperature-dependent change
      in rate-limiting step within the chemical manifold of acylation, but supports a
      mechanism in which an isomerization of enzyme conformation is coupled to active
      site chemistry. We finally suggest that the near absolute temperature
      independence of 15N-KIE may point to a unique transition state for this process.

PMID- 14730980
TI  - Reactions of 4-oxalocrotonate tautomerase and YwhB with 3-halopropiolates:
      analysis and implications.
AB  - 4-Oxalocrotonate tautomerase (4-OT) and YwhB, a 4-OT homologue found in Bacillus
      subtilis, exhibit a low level hydratase activity that converts trans-3
      haloacrylates to acetaldehyde, presumably through a malonate semialdehyde
      intermediate. The mechanism for the initial transformation of the 3-haloacrylate
      to malonate semialdehyde involves Pro-1 as well as an arginine, two residues that
      play critical roles in the 4-OT-catalyzed isomerization reaction and the YwhB
      catalyzed tautomerization reaction. These residues are also critical for the
      trans-3-chloroacrylic acid dehalogenase (CaaD)-catalyzed conversion of trans-3
      haloacrylates to malonate semialdehyde. Recently, 3-bromo- and 3
      chloropropiolate, the acetylene analogues of 3-haloacrylates, were characterized
      as potent irreversible inhibitors of CaaD due to the covalent modification of the
      catalytic proline. In view of these observations, an investigation of the
      behavior of 4-OT and YwhB with the 3-halopropiolates was undertaken. The results
      show that these compounds are potent irreversible inhibitors of 4-OT and YwhB
      with Pro-1 being the sole site of covalent modification by 3-bromopropiolate. The
      inactivation process could involve the enzyme-catalyzed addition of water to the
      3-halopropiolate yielding an acyl halide, which would inactivate the enzyme or be
      initiated by the nucleophilic attack of Pro-1 at the C-3 position of the 3
      halopropiolate in a Michael type reaction. The presence of the halogen along with
      Arg-11 could facilitate both reactions with the latter causing the polarization
      of the alpha,beta-unsaturated acids. The 3-halopropiolates are the first
      identified inhibitors of YwhB and confirm the importance of Pro-1 in its
      mechanism. In addition, the results set the stage for the use of these compounds
      as mechanistic probes of the primary as well as low level activities of 4-OT and
      YwhB.

PMID- 14730981
TI  - Cloning, expression, and characterization of a cis-3-chloroacrylic acid
      dehalogenase: insights into the mechanistic, structural, and evolutionary
      relationship between isomer-specific 3-chloroacrylic acid dehalogenases.
AB  - The gene encoding the cis-3-chloroacrylic acid dehalogenase (cis-CaaD) from
      coryneform bacterium strain FG41 has been cloned and overexpressed, and the
      enzyme has been purified to homogeneity and subjected to kinetic and mechanistic
      characterization. Kinetic studies show that cis-CaaD processes cis-3
      haloacrylates, but not trans-3-haloacrylates, with a turnover number of
      approximately 10 s(-1). The product of the reaction is malonate semialdehyde,
      which was confirmed by its characteristic 1H NMR spectrum. The enzyme shares low
      but significant sequence similarity with the previously studied trans-3
      chloroacrylic acid dehalogenase (CaaD) and with other members of the 4
      oxalocrotonate tautomerase (4-OT) family. While 4-OT and CaaD function as homo-
      and heterohexamers, respectively, cis-CaaD appears to be a homotrimeric protein
      as assessed by gel filtration chromatography. On the basis of the known three
      dimensional structures and reaction mechanisms of CaaD and 4-OT, a sequence
      alignment implicated Pro-1, Arg-70, Arg-73, and Glu-114 as important active-site
      residues in cis-CaaD. Subsequent site-directed mutagenesis experiments confirmed
      these predictions. The acetylene compounds, 2-oxo-3-pentynoate and 3-bromo- and 3
      chloropropiolate, were processed by cis-CaaD to products consistent with an
      enzyme-catalyzed hydration reaction previously established for CaaD. Hydration of
      2-oxo-3-pentynoate afforded acetopyruvate, while the 3-halopropiolates became
      irreversible inhibitors that modified Pro-1. The results of this work revealed
      that cis-CaaD and CaaD have different primary and quaternary structures, and
      display different substrate specificity and catalytic efficiencies, but likely
      share a highly conserved catalytic mechanism. The mechanism may have evolved
      independently because sequence analysis indicates that cis-CaaD is not a 4-OT
      family member, but represents the first characterized member of a new family in
      the tautomerase superfamily that probably resulted from an independent
      duplication of a 4-OT-like sequence. The discovery of a fifth family of enzymes
      within this superfamily further demonstrates the diversity of activities and
      structures that can be created from 4-OT-like sequences.

PMID- 14730982
TI  - A pair of membrane-embedded acidic residues in the NuoK subunit of Escherichia
      coli NDH-1, a counterpart of the ND4L subunit of the mitochondrial complex I, are
      required for high ubiquinone reductase activity.
AB  - The ND4L subunit of mitochondrial NADH:ubiquinone oxidoreductase (complex I) is
      an integral membrane protein that contains two highly conserved glutamates within
      putative trans-membrane helices. We employed complex I from Escherichia coli (NDH
      1) to study the role of these residues by site-directed mutagenesis. The
      conserved glutamates of the NuoK subunit, E36 and E72, were replaced by either
      Asp or Gln residues, and the effects of the mutations on cell growth and
      catalysis of electron transfer from deamino-NADH to ubiquinone analogues were
      examined. Additional mutants that carried acidic residues at selected positions
      within this domain were also prepared and analyzed. The results indicated that
      two closely located membrane-embedded acidic residues in NuoK are essential for
      high rates of ubiquinone reduction, a prerequisite for the growth of cytochrome
      bo-deficient E. coli cells on malate as the main carbon source. The two acidic
      residues do not have to be on adjacent helices, and mutual location on the same
      helix, either helix 2 or 3, at an interval of three amino acids (about one turn
      of the putative helix), resulted in high activity and good growth phenotypes.
      Nevertheless, shifting only one of them, either E36 or E72, toward the
      periplasmic side of the membrane by about one turn of the helix severely hampered
      activity and growth, whereas moving both acidic residues together to that deeper
      membrane position stimulated the ubiquinone reductase activity of the enzyme but
      not cell growth on malate, suggesting impaired energy conservation in this
      mutant.

PMID- 14730983
TI  - Electrochemical studies of the mono-Fe, Fe-Zn, and Fe-Fe metalloisoforms of
      bacteriophage lambda protein phosphatase.
AB  - Bacteriophage lambda protein phosphatase (lambdaPP) is a member of a large
      superfamily of metallophosphoesterases, including serine/threonine protein
      phosphatases, purple acid phosphatases, 5'-nucleotidase, and DNA repair enzymes
      such as Mre11. Members of this family share several common characteristics,
      including a common phosphoesterase motif, secondary structural fold
      (betaalphabetaalphabeta), and metal ligand environment, and often accommodate a
      dinuclear metal center. The identity of the active site metals often differs
      between family members. Despite the extensive spectroscopic studies of several
      family members, only the standard redox potential of porcine purple acid
      phosphate (PAP) has been measured. In this report, we investigate the redox
      properties of another member of this protein family. The standard redox
      potentials of the mono-Fe, Fe-Zn, and Fe-Fe metalloisoforms of lambdaPP were
      determined from anaerobic redox titration experiments. Two different S = 5/2,
      mono-Fe3+ lambdaPP species were identified: the first with an E/D approximately
      0.17, g = 8.9 and 4.8, and an Eo' approximately +130 mV; the second with E/D
      approximately 0.05, g = 6.7, 5.9, and 4.4, and an Eo' approximately +120 mV. The
      first and second mono-Fe3+ species are thought to represent Fe present in the M2
      and M1 sites, respectively. The addition of Zn2+ to mono-Fe3+ lambdaPP results in
      a decrease in both mono-Fe3+ species and the appearance of a new S = 5/2, Fe(3+)
      Zn2+ species (E/D approximately 0.02, g = 5.9, and an Eo' > +175 mV). The Fe-Fe
      lambdaPP titration revealed an S = 1/2, Fe(3+)-Fe2+ (g < 2) species with an Eo' >
      +128 mV. These results suggest that the active site of lambdaPP supports a high
      oxidation potential for both metal sites and may indicate an equally oxidizing
      active site for other member metallophosphoesterases.

PMID- 14730984
TI  - Superoxide destroys the [2Fe-2S]2+ cluster of FNR from Escherichia coli.
AB  - The oxygen sensing ability of the transcription factor FNR depends on the
      presence of a [4Fe-4S]2+ cluster. In the presence of O2, conversion of the [4Fe
      4S]2+ cluster to a [2Fe-2S]2+ cluster inactivates FNR, but the fate of the [2Fe
      2S]2+ cluster in cells grown under aerobic conditions is unknown. The present
      study shows that the predominant form of FNR in aerobic cells is apo-FNR (cluster
      less FNR) indicating that the [2Fe-2S]2+ cluster, like the [4Fe-4S]2+ cluster, is
      not stable under these conditions. By quantifying the amount of [2Fe-2S]2+
      cluster in 2Fe-FNR in vitro in the presence of various reductants and oxidants
      (GSH, DTT, cysteine, O2, hydrogen peroxide, and superoxide), we found that
      superoxide, a byproduct of aerobic metabolism, significantly destabilized the
      [2Fe-2S]2+ cluster. Mossbauer spectroscopy was used to monitor the effects of
      superoxide on 2Fe-FNR in vivo; under cellular conditions that favored superoxide
      production, we observed the disappearance of the signal representative of the
      [2Fe-2S]2+ cluster. We conclude that the [2Fe-2S]2+ cluster of FNR is labile to
      superoxide both in vitro and in vivo. This lability may explain the absence of
      the [2Fe-2S]2+ cluster form of FNR under aerobic growth conditions.

PMID- 14730985
TI  - Voltammetric studies of the catalytic mechanism of the respiratory nitrate
      reductase from Escherichia coli: how nitrate reduction and inhibition depend on
      the oxidation state of the active site.
AB  - The respiratory molybdoenzyme nitrate reductase (NarGHI) from Escherichia coli
      has been studied by protein film voltammetry, with the enzyme adsorbed on a
      rotating disk pyrolytic graphite edge (PGE) electrode. Catalytic voltammograms
      for nitrate reduction show a complex wave consisting of two components that vary
      with pH, nitrate concentration, and the presence of inhibitors. At micromolar
      levels of nitrate, the activity reaches a maximum value at approximately -25 mV
      and then decreases as the potential becomes more negative. As the nitrate
      concentration is raised, the activity at more negative potentials increases and
      eventually becomes the dominant feature at millimolar concentrations. This leads
      to the hypothesis that nitrate binds more tightly to Mo(V) than Mo(IV), so that
      low levels of nitrate are more effectively reduced at a higher potential despite
      the lower driving force. However, an alternative interpretation, that nitrate
      binding is affected by a change in the redox state of the pterin, cannot be ruled
      out. This proposal, implicating a specific redox transition at the active site,
      is supported by experiments carried out using the inhibitors azide and
      thiocyanate. Azide is the stronger inhibitor of the two, and each inhibitor shows
      two inhibition constants, one at high potential and one at low potential, both of
      which are fully competitive with nitrate; closer analysis reveals that the
      inhibitors act preferentially upon the catalytic activity at high potential. The
      unusual potential dependence therefore derives from the weaker binding of nitrate
      or the inhibitors to a more reduced state of the active site. The possible
      manifestation of these characteristics in vivo has interesting implications for
      the bioenergetics of E. coli.

PMID- 14730986
TI  - Superoxide reductase from Desulfoarculus baarsii: identification of protonation
      steps in the enzymatic mechanism.
AB  - Superoxide reductase (SOR) is a metalloenzyme that catalyzes the reduction of O2*
      to H2O2 and provides an antioxidant mechanism in some anaerobic and
      microaerophilic bacteria. Its active site contains an unusual mononuclear ferrous
      center (center II). Protonation processes are essential for the reaction
      catalyzed by SOR, since two protons are required for the formation of H2O2. We
      have investigated the acido-basic and pH dependence of the redox properties of
      the active site of SOR from Desulfoarculus baarsii, both in the absence and in
      the presence of O2*-. In the absence of O2*-, the reduction potential and the
      absorption spectrum of the iron center II exhibit a pH transition. This is
      consistent with the presence of a base (BH) in close proximity to the iron center
      which modulates its reduction properties. Studies of mutants of the closest
      charged residues to the iron center II (E47A and K48I) show that neither of these
      residues are the base responsible for the pH transitions. However, they both
      interact with this base and modulate its pKa value. By pulse radiolysis, we
      confirm that the reaction of SOR with O2*- involves two reaction intermediates
      that were characterized by their absorption spectra. The precise step of the
      catalytic cycle in which one protonation takes place was identified. The
      formation of the first reaction intermediate, from a bimolecular reaction of SOR
      with O2*-, does not involve proton transfer as a rate-limiting step, since the
      rate constant k1 does not vary between pH 5 and pH 9.5. On the other hand, the
      rate constant k2 for the formation of the second reaction intermediate is
      proportional to the H+ concentration in solution, suggesting that the proton
      arises directly from the solvent. In fact, BH, E47, and K48 have no role in this
      step. This is consistent with the first intermediate being an iron(III)-peroxo
      species and the second one being an iron(III)-hydroperoxo species. We propose
      that BH may be involved in the second protonation process corresponding to the
      release of H2O2 from the iron(III)-hydroperoxo species.

PMID- 14730987
TI  - Both the D-(+) and L-(-) enantiomers of nicotine inhibit Abeta aggregation and
      cytotoxicity.
AB  - The underlying cause of Alzheimer's disease is thought to be the aggregation of
      monomeric beta-amyloid (Abeta), through a series of toxic oligomers, which forms
      the mature amyloid fibrils that accumulate at the center of senile plaques. It
      has been reported that L-(-)-nicotine prevents Abeta aggregation and toxicity,
      and inhibits senile plaque formation. Previous NMR studies have suggested that
      this could be due to the specific binding of L-(-)-nicotine to histidine residues
      (His6, His13, and His14) in the peptide. Here, we have looked at the effects of
      both of the L-(-) and D-(+) optical enantiomers of nicotine on the aggregation
      and cytotoxicity of Abeta(1-40). Surprisingly, both enantiomers inhibited
      aggregation of the peptide and reduced the toxic effects of the peptide on cells.
      In NMR studies with Abeta(1-40), both enantiomers of nicotine were seen to
      interact with the three histidine residues. Overall, our data indicate that
      nicotine can delay Abeta fibril formation and maintain a population of less toxic
      Abeta species. This effect cannot be due to a highly specific binding interaction
      between nicotine and Abeta, as previously thought, but could be due instead to
      weaker, relatively nonspecific binding, or to the antioxidant or metal chelating
      properties of nicotine. D-(+)-nicotine, being biologically much less active than
      L-(-)-nicotine, might be a useful therapeutic agent.

PMID- 14730988
TI  - Cholesterol oxidase senses subtle changes in lipid bilayer structure.
AB  - We investigated the dependence of cholesterol oxidase catalytic activity and
      membrane affinity on lipid structure in model membrane bilayers. The binding
      affinities of cholesterol oxidase to 100-nm unilamellar vesicles composed of
      mixtures of DOPC or DPPC and cholesterol are not sensitive to cholesterol mole
      fraction if the phase of the membrane is in a fluid state. When the membrane is
      in a solid-ordered state, the binding affinity of cholesterol oxidase increases
      approximately 10-fold. The second-order rate constants (kcat*/Km*) for different
      lipid mixtures show a 2-fold substrate specificity for cholesterol in the l(d)
      phase of high cholesterol chemical activity over cholesterol in the l(o) phase.
      Moreover, the enzyme is 2-fold more specific for cholesterol in the l(o) phase
      than in the s(o) phase. Likewise, there is 2-fold substrate specificity for the
      high cholesterol chemical activity l(d) phase over the low chemical activity l(d)
      phase. The specificities for the l(d) phase of low cholesterol chemical activity
      and the l(o) phase are the same. These data indicate that the more ordered the
      lipid cholesterol structure in the bilayer, the lower the catalytic rate.
      However, under all of the conditions investigated, the enzyme is never saturated
      with substrate. The enzymatic activity directly reflects the facility with which
      cholesterol can move out of the membrane, whether changes in cholesterol transfer
      facility are due to phase changes or more localized changes in packing. We
      conclude that the activity of cholesterol oxidase is directly and sensitively
      dependent on the physical properties of the membrane in which its substrate is
      bound.

PMID- 14730989
TI  - Supramolecular metal-organometallic coordination networks based on quinonoid pi
      complexes.
AB  - The use of organometallic pi-complexes in the coordination-directed self-assembly
      of polymeric structures is a new area with many potential applications.
      Supramolecular metal-organometallic coordination networks (MOMNs), which are
      described herein, consist of metal ion or metal cluster nodes connected by
      bifunctional "organometalloligands" that serve as spacers. The
      organometalloligand utilized in this work is the stable anionic complex (eta(4)
      benzoquinone)Mn(CO)(3)(-) (p-QMTC), which binds through both quinone oxygen atoms
      to generate MOMNs having both backbone and pendant metal sites. In many cases the
      MOMNs are obtained as neutral and thermally stable solids, with molecular
      structures that depend on the geometrical and electronic requirements of the
      metal nodes, the solvent, and the presence of organic spacers. Redox-active
      quinone-based organometallic pi-complexes permit the construction of an
      impressive range of coordination network architectures and hold much promise for
      the development of functional materials.

PMID- 14730990
TI  - Photoreceptor proteins, "star actors of modern times": a review of the functional
      dynamics in the structure of representative members of six different
      photoreceptor families.
AB  - Six well-characterized photoreceptor families function in Nature to mediate light
      induced signal transduction: the rhodopsins, phytochromes, xanthopsins,
      cryptochromes, phototropins, and BLUF proteins. The first three catalyze E/Z
      isomerization of retinal, phytochromobilin, and p-coumaric acid, respectively,
      while the last three all have a different flavin-based photochemistry. For many
      of these photoreceptor proteins, (many of) the details of the conversion of the
      light-induced change in configuration of their chromophore into a signaling state
      and eventually a biological response have been resolved. Some members of the
      rhodopsins, the xanthopsins, and the phototropins are so well characterized that
      they function as model systems to study (receptor) protein dynamics and
      (un)folding.

PMID- 14730991
TI  - Recent advances in synthetic transformations mediated by cerium(IV) ammonium
      nitrate.
AB  - Cerium(IV) ammonium nitrate (CAN) has recently emerged as a versatile reagent for
      oxidative electron transfer; the overwhelming number of reports serve as a
      testimony to the unparalleled utility of CAN in a variety of transformations of
      synthetic importance. Our recent work has uncovered novel carbon-carbon bond
      forming reactions leading to the one-pot synthesis of dihydrofurans,
      tetrahydrofurans, and aminotetralins. In addition, we have developed a number of
      facile carbon-heteroatom bond-forming reactions by the CAN-mediated oxidative
      addition of soft anions to alkenes. A mechanistic rationale has been provided for
      the reactions explored. As might be expected of very powerful one-electron
      oxidants, the chemistry of cerium(IV) oxidation of organic molecules is dominated
      by radical and radical cation chemistry.

PMID- 14730992
TI  - Recent highlights in electrophilic fluorination with 1-chloromethyl-4-fluoro- 1,4
      diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate).
AB  - Synthetic and structural aspects of organofluorine compounds continue to be the
      focal points of vigorous research activities, as evidenced by the appearance of a
      large number of publications. Among the various useful methodologies for the
      introduction of fluorine into organic molecules, electrophilic fluorination is a
      promising and exciting area of research. While a variety of electrophilic
      fluorinating reagents are available, currently 1-chloromethyl-4-fluoro-1,4
      diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) provides a
      remarkably straightforward and effective route. The breadth of applications
      realizable from this reagent in its role as a key electrophilic fluorinating
      reagent is highlighted here. This Account covers the literature for electrophilic
      fluorination reactions that employ Selectfluor during the period January 1999
      January 2003.

PMID- 14730993
TI  - Dynamics of antioxidant action of vitamin E.
AB  - Vitamin E is the major lipophilic, radical-scavenging antioxidant in vivo and
      protects humans from the oxidative stress mediated by active oxygen and nitrogen
      species. The mechanisms of the inhibition of oxidation by vitamin E in vitro are
      now fairly well understood, but the dynamics of antioxidant action of vitamin E
      in vivo have not been well elucidated yet, primarily because of the inherent
      heterogeneity of biological systems. In this Account, the factors which determine
      the antioxidant capacity of vitamin E are discussed, and the importance of its
      localization and mobility in the membranes and lipoproteins is emphasized.

PMID- 14730994
TI  - Petroleomics: the next grand challenge for chemical analysis.
AB  - Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry
      has recently revealed that petroleum crude oil contains heteroatom-containing
      (N,O,S) organic components having more than 20,000 distinct elemental
      compositions (C(c)H(h)N(n)O(o)S(s)). It is therefore now possible to contemplate
      the ultimate characterization of all of the chemical constituents of petroleum,
      along with their interactions and reactivity, a concept we denote as
      "petroleomics". Such knowledge has already proved capable of distinguishing
      petroleum and its distillates according to their geochemical origin and maturity,
      distillation cut, extraction method, catalytic processing, etc. The key features
      that have opened up this new field have been (a) ultrahigh-resolution FT-ICR mass
      analysis, specifically, the capability to resolve species differing in elemental
      composition by C(3) vs SH(4) (i.e., 0.0034 Da); (b) higher magnetic field to
      cover the whole mass range at once; (c) dynamic range extension by external mass
      filtering; and (d) plots of Kendrick mass defect vs nominal Kendrick mass as a
      means for sorting different compound "classes" (i.e., numbers of N, O, and S
      atoms), "types" (rings plus double bonds), and alkylation ((-CH(2))(n))
      distributions, thereby extending to >900 Da the upper limit for unique assignment
      of elemental composition based on accurate mass measurement. The same methods are
      also being applied successfully to analysis of humic and fulvic acids, coals, and
      other complex natural mixtures, often without prior or on-line chromatographic
      separation.

PMID- 14730996
TI  - Pushing the frontiers of hard and soft scorpionate chemistry.
AB  - The preparation and structure of the first scorpionate complex of a group 16
      element, [Te(kappa(2)-Tm(Me))(2)], is reported. It displays square planar
      geometry at the Te atom and two distinct ligand conformations. In addition, the
      first pyrazolylborate complex of a group 15 element, [Bi(Tp)(2)(pzH)Cl], has been
      synthesized and characterized.

PMID- 14730995
TI  - A fluorescent intercalator displacement assay for establishing DNA binding
      selectivity and affinity.
AB  - A summary of the qualitative and quantitative elements of a fluorescent
      intercalator displacement (FID) assay useful for establishing the DNA binding
      selectivity, affinity, stoichiometry, and binding site size and distinguishing
      modes of DNA binding is provided.

PMID- 14730997
TI  - Sensitization of TiO(2) by supramolecules containing zinc porphyrins and
      ruthenium-polypyridyl complexes.
AB  - Modification of wide band gap semiconductor surfaces by a new generation of
      supramolecular sensitizers combining porphyrin and ruthenium-polypyridyl
      complexes leads to versatile molecular interfaces, allowing the exploitation of
      photoinduced charge transfer in photoelectrochemical devices.

PMID- 14730998
TI  - Synthesis and characterization of cyclotetraphosphato complexes of Rh(I), Ir(I),
      Ru(II), and Pd(II).
AB  - The cyclotetraphosphate ion (P(4)O(12)(4)(-)) as a PPN (PPN = (PPh(3))(2)N(+))
      salt reacts with [MCl(cod)](2) (M = Rh, Ir; cod = 1,5-cyclooctadiene) to give the
      dinuclear complexes (PPN)(2)[[M(cod)](2)(P(4)O(12))], in which the two metal
      moieties are situated trans to each other with respect to the P(4)O(4) ring in
      the solid state. In solution, however, these complexes exist as mixtures of trans
      and cis isomers. On the other hand, the P(4)O(12)(4)(-) ion reacts with 4 equiv
      of [Rh(cod)(MeCN)(x)](+) cation to give the tetranuclear complex
      [[Rh(cod)](4)(P(4)O(12))], where the four Rh(cod) fragments are bound to the
      P(4)O(12) platform alternately on both sides of the P(4)O(4) ring. Dinuclear
      P(4)O(12) complexes of ruthenium and palladium are also synthesized.

PMID- 14730999
TI  - X-ray absorption spectroscopy of selenate reductase.
AB  - The metal sites of selenate reductase from Thauera selenatis have been
      characterized by Mo, Se, and Fe K-edge X-ray absorption spectroscopy. The Mo site
      of the oxidized enzyme has 3 to 4 sulfur ligands at 2.33 A from two molybdopterin
      cofactors, one Mo=O group at 1.68 A and one Mo-O with an intermediate bond length
      of 1.81 A. The reduced enzyme has a des-oxo active site, again with about four Mo
      S ligands (at 2.32 A) and possibly one oxygen ligand at 2.22 A. The enzyme was
      found to contain Se in a reduced form (probably organic) although the sequence
      does not indicate the presence of selenocysteine. The Se is coordinated to both a
      metal (probably Fe) and a lighter scatterer such as carbon.

PMID- 14731000
TI  - The unexpected motional isotropy of the tin atom in a tricoordinate stannylium
      cation.
AB  - The dynamics of the metal atom in the recently isolated tricoordinate tin complex
      tris(2,4,6-triisopropylphenyl)stannylium tetrakis(pentafluorophenyl)borate was
      examined by temperature-dependent (119)Sn Mossbauer spectroscopy over the
      temperature range 90 K < T < 170 K. Contrary to expectation, the metal atom
      motion in this temperature range is isotropic within experimental error of the
      Mossbauer data, and is only moderately anisotropic, even at 293 K, as evidenced
      by single crystal X-ray diffraction data. The hyperfine parameters at 90 K are
      completely consistent with trigonal coordination involving sp(2) hybridization of
      the 5s5p bonding orbitals of tin.

PMID- 14731001
TI  - Probing the solvent accessibility and electron density of adenine: oxidation of 7
      deazaadenine in bent DNA and purine doublets.
AB  - The effect of DNA bending on nucleobase electron transfer was investigated by
      studying the oxidation of double-stranded sequences containing seven repeats of
      the known bent sequence d(GGCA(1)A(2)A(3)A(4)A(5)A(6)C) where 7-deazaadenine (zA)
      was substituted at the A(3) position. Native gel electrophoresis was used to show
      that the sequence remained bent upon substitution of zA, which provides for
      oxidation of the sequence by Ru(bpy)(3)(3+) (bpy = 2,2'-bipyridine). The Ru(III)
      oxidant was generated by photolysis of Ru(bpy)(3)(2+) in the presence of
      ferricyanide, and the oxidation was visualized by high-resolution gel
      electrophoresis of the radiolabeled DNA sequence following base treatment.
      Cleavage of the DNA strand at the guanine residues and at the zA residues was
      observed. Comparison of the oxidation of zA in bent DNA versus the normal B form
      showed that hybridization of the B form sequence to its Watson-Crick complement
      produced a reduction in cleavage by a factor of 5.19 +/- 0.46 while hybridization
      of the bent sequence only reduced cleavage by a factor of 1.58 +/- 0.23. This
      result implies that the zA in the double-stranded, bent sequence is much more
      solvent-exposed than in normal B-form DNA. When the zA occurred in a B-form 5'-zA
      G doublet, the reactivity was 6.63 +/- 0.10 times higher for the zA compared to
      the G. This implies an even greater effect of a 3'-guanine on the oxidation
      potential of zA than in the well-known 5'-GG doublet.

PMID- 14731002
TI  - Syntheses and thermal reactivities of tetradentate metalloenediynes of Cu(II) and
      Zn(II).
AB  - The syntheses and Bergman cyclization temperatures of disubstituted tetradentate
      enediyne ligands based on a dibenzylethylenediamine backbone are reported
      relative to the corresponding Cu(II) and Zn(II) analogues. For these compounds,
      the R-groups dimethylamine (dma), pyridine (py), quinoline (quin), and 3
      oxypyridine (pyO) have been symmetrically and asymmetrically incorporated at the
      alkyne termini positions directly (0:0) or via a methylene spacer (1:0, 0:1,
      1:1). Electron paramagnetic resonance (EPR) reveals that all Cu(II) complexes are
      monomeric with near axial symmetry and g-values (g(x) approximately 2.04, g(y)
      approximately 2.09 g(z) approximately 2.25) representative of tetragonal Cu(II)
      geometries. The hyperfine splitting parameter A(z) values are approximately 170 x
      10(-)(4) cm(-)(1), which is consistent with distorted 4-coordinate, or weakly 6
      coordinate, structures. In contrast, solution conductivity measurements show that
      Zn(II) complexes with rigid py or quin ligands (e.g., py-py 0:0, py-quin 0:0)
      behave as 1:4 electrolytes indicative of dimeric, bridging enediyne structures.
      Consequently, these Zn(II) complexes have very high Bergman cyclization
      temperatures (>290 degrees C), while their less rigid, 1:1 analogues (<185
      degrees C) and monomeric Cu(II) counterparts (110-136 degrees C) have markedly
      lower cyclization temperatures. The results underscore the important consequences
      metal center structure plays in influencing Bergman cyclization temperatures of
      metalloenediynes.

PMID- 14731003
TI  - Dinuclear complexes of chiral tetradentate pyridylimine ligands:
      diastereoselectivity, positive cooperativity, anion selectivity, ligand self
      sorting based on chirality, and magnetism.
AB  - The synthesis and coordination chemistry of two chiral tetradentate pyridylimine
      Schiff base ligands are reported. The ligands were prepared by the nucleophilic
      displacement of both bromides of 1,3-bis(bromomethyl)benzene (2) or 3,5
      bis(bromomethyl)toluene (3) by the anion of (S)-valinol, followed by capping of
      both amine groups with pyridine-2-carboxaldehyde. Both ligands react with CoCl(2)
      and NiCl(2) to give [M(2)L(2)Cl(2)](2+) complexes. Remarkably, neither fluoride
      nor bromide ions can act as bridging ligands. The formation of [Co(2)((S)
      3)(2)Cl(2)](2+) is highly diastereoselective, and X-ray crystallography shows
      that both metal centers in the [Co(2)((S)-3)(2)Cl(2)](CoCl(4)) complex adopt the
      lambda configuration (crystal data:
      [Co(2)(C(31)H(40)N(4)O(2))(2)Cl(2)](CoCl(4)).(CH(3)CN)(3), monoclinic, P2(1), a =
      11.595(2) A, b = 22.246(4) A, c = 15.350(2) A, V = 3705(1) A(3), beta =
      110.643(3) degrees, Z = 2). Structurally, the dinuclear complex can be viewed as
      a helicate with the helical axis running perpendicular to the [Co(2)Cl(2)] plane.
      The reaction of racemic 2 with CoCl(2) was shown by (1)H NMR spectroscopy to
      yield a racemic mixture of Lambda,Lambda-[Co(2)((S)-2)(2)Cl(2)](2+) and
      delta,delta-[Co(2)((R)-2)(2)Cl(2)](2+) complexes; that is, a homochiral
      recognition process takes place. Spectrophotometric titrations were performed by
      titrating (S)-3 with Co(ClO(4))(2) followed by Bu(4)NCl, and the global stability
      constants of [Co((S)-3)](2+) (log beta(110) = 5.7), [Co((S)-3)(2)](2+) (log
      beta(120) = 11.6), and [Co(2)((S)-3)(2)Cl(2)](2+) (log beta(110) = 23.8) were
      calculated. The results revealed a strong positive cooperativity in the formation
      of [Co(2)((S)-3)(2)Cl(2)](2+). Variable-temperature magnetic susceptibility
      curves for [Co(2)((S)-2)(2)Cl(2)](BPh(4))(2) and [Co(2)((S)
      3)(2)Cl(2)](BPh(4))(2) are very similar and indicate that there are no
      significant magnetic interactions between the cobalt(II) centers.

PMID- 14731004
TI  - Hybrid cluster-cages formed via cyanometalate condensation: Cs subset
      Co(4)Ru(6)S(2)(CN)(12), Co(4)Ru(9)S(6)(CN)(9), and Rh(4)Ru(9)S(6)(CN)(9)
      frameworks.
AB  - Condensation of cyanometalates and cluster building blocks leads to the formation
      of hybrid molecular cyanometalate cages. Specifically, the reaction of [Cs subset
      [CpCo(CN)(3)](4)[CpRu](3)] and [(cymene)(2)Ru(3)S(2)(NCMe)(3)]PF(6) produced [Cs
      subset [CpCo(CN)(3)](4)[(cymene)(2)Ru(3)S(2)][CpRu](3)](PF(6))(2), Cs subset
      Co(4)Ru(6)S(2)(2+). Single-crystal X-ray diffraction, NMR spectroscopy, and ESI
      MS measurements show that Cs subset Co(4)Ru(6)S(2)(2+ ) consists of a
      Ru(4)Co(4)(CN)(12) box fused with a Ru(3)S(2) cluster via a common Ru atom. The
      reaction of PPN[CpCo(CN)(3)] and 0.75 equiv of
      [(cymene)(2)(MeCN)(3)Ru(3)S(2)](PF(6))(2) in MeCN solution produced
      [[CpCo(CN)(3)](4)[(cymene)(2)Ru(3)S(2)](3)](PF(6))(2), Co(4)Ru(9)S(6)(2+).
      Crystallographic analysis, together with NMR and ESI-MS measurements, shows that
      Co(4)Ru(9)S(6)(2+ ) consists of a Ru(3)Co(4)(CN)(9) "defect box" core, wherein
      each Ru is fused to a Ru(3)S(2) clusters. The analogous condensation using
      [CpRh(CN)(3)](-) in place of [CpCo(CN)(3)](-) produced the related cluster-cage
      Rh(4)Ru(9)S(6)(2+). Electrochemical analyses of both Co(4)Ru(9)S(6)(2+) and
      Rh(4)Ru(9)S(6)(2+) can be rationalized in the context of reduction at the cluster
      and the Co(III) subunits, the latter being affected by the presence of alkali
      metal cations.

PMID- 14731005
TI  - R(6)TT'(2), new variants of the Fe(2)P structure type. Sc(6)TTe(2) (T = Ru, Os,
      Rh, Ir), Lu(6)MoSb(2), and the anti-typic Sc(6)Te(0.80)Bi(1.68).
AB  - The Fe(2)P structure (P62m) features two 3-fold Fe positions and both 2-fold and
      1-fold P sites, and variations in occupancies of the latter pair yield the
      reported diversity of results. The known Sc(6)TTe(2) examples for T = Fe-Ni are
      herein extended to four heavier transition metal T derivatives. An attempt to
      synthesize bismuth analogues led to the novel inverse derivative in which
      fractional Te (vice T) occupies the smaller tricapped trigonal prismatic (TTP) Sc
      polyhedron, and Bi rather than Te occurs in the larger TTP of Sc, with parallel
      reversal of polarity in the bonding. The reported Lu(8)Te, which is distributed
      as Lu(6)TeLu(2), is the only example in which a transition metal occupies the
      normal 2-fold P or Te non-metal position, with corresponding large effects on the
      bonding. Lutetium otherwise does not form R(6)TTe(2) analogues, but the novel
      Lu(6)MoSb(2) isotype occurs instead. Extended Huckel calculations are presented
      for five examples, and the structural and bonding regularities and varieties are
      discussed further.

PMID- 14731006
TI  - A variable Ag-Cr-Oxalate channel lattice: [M(x)Ag(0.5)(
      )(x)(H(2)O)(3)]@[Ag(2.5)Cr(C(2)O(4))(3)], M = K, Cs, Ag.
AB  - Reaction of aqueous AgNO(3) with aqueous M(3)[Cr(ox)(3)] in >or=3:1 molar ratio
      causes the rapid growth of large, cherry-black, light-stable crystals which are
      not Ag(3)[Cr(ox)(3)], but [M(0.5)(H(2)O)(3)]@[Ag(2.5)Cr(ox)(3)] (ox(2)(-) =
      oxalate, C(2)O(4)(2)(-); M = Na, K, Cs, Ag, or mixtures of Ag and a group 1
      element). The structure of these crystals contains an invariant channeled
      framework, with composition [[Ag(2.5)Cr(ox)(3)](-)(0.5)]( infinity ), constructed
      with [Cr(ox)(3)] coordination units linked by Ag atoms through centrosymmetric
      [Cr-O(2)C(2)O(2)-Ag](2) double bridges. The framework composition
      [Ag(2.5)Cr(ox)(3)](-)(0.5) occurs because one Ag is located on a 2-fold axis.
      Within the channels there is a well-defined and ordered set of six water
      molecules, strongly hydrogen bonded to each other and some of the oxalate O
      atoms. This invariant channel plus water structure accommodates group 1 cations,
      and/or Ag cations, in different locations and in variable proportions, but always
      coordinated by channel water and some oxalate O atoms. The general formulation of
      these crystals is therefore [M(x)Ag(0.5-x)(H(2)O)(3)]@[Ag(2.5)Cr(ox)(3)]. Five
      different crystals with this structure are reported, with compositions 1
      Ag(0.5)[Ag(2.5)Cr(ox)(3)](H(2)O)(3), 2
      Cs(0.19)Ag(0.31)[Ag(2.5)Cr(ox)(3)](H(2)O)(3), 3
      K(0.28)Ag(0.22)[Ag(2.5)Cr(ox)(3)](H(2)O)(3), 4
      Cs(0.41)Ag(0.09)[Ag(2.5)Cr(ox)(3)](H(2)O)(3), and 5 Cs(0.43)Ag(0.07)
      [Ag(2.5)Cr(ox)(3)](H(2)O)(3). All crystallize in space group C2/c, with a
      approximately 18.4, b approximately 14.6, c approximately 12.3 A, beta
      approximately 113 degrees. Pure Ag(3)[Cr(ox)(3)](H(2)O)(3), which has the same
      crystal structure (1), was obtained from water by treating Li(3)[Cr(ox)(3)] with
      excess AgNO(3). Complete dehydration of all of these compounds occurs between 30
      and 100 degrees C, with loss of diffraction, but rehydration by exposure to
      H(2)O(g) at ambient temperature leads to recovery of the original diffraction
      pattern. In single crystals, this reversible dehydration-hydration occurs without
      visually evident crystal change, but with loss of mechanical strength. We
      postulate a general mechanism for transport of water molecules along the
      channels, associated with local partial collapses of the channel framework, with
      concomitant bending but little breaking of the host Ag-O and Cr-O bonds, which is
      readily reversed.

PMID- 14731007
TI  - Solvent-dependent coordination polymers: cobalt complexes of 3,5-dinitrobenzoic
      acid and 3,5-dinitro-4-methylbenzoic acid with 4,4'-bipyrdine.
AB  - The synthesis, structure elucidation, and analysis of the self-assembly of Co(II)
      complexes of 3,5-dinitrobenzoic acid and 3,5-dinitro-4-methylbenzoic acid with
      4,4'-bipyridine have been reported. Formation of the complexes and the self
      assembly in the three-dimensional structures have been found to be dependent on
      the solvents (such as acetone, dimethly sulfoxide, etc.) employed for the
      synthesis of the aggregates. 3,5-Dinitrobenzoic acid forms two coordination
      polymers, 1a and 1b, from methanol and a mixture of methanol and acetone
      solvents, respectively, with entirely different recognition patterns. Similarly,
      3,5-dinitro-4-methylbenzoic acid also forms two coordination complexes, 2a and
      2b, incorporating the solvent of the reaction medium into the crystal lattice.
      Complex 2a forms a solvated channel structure, whereas 2b gives a bilayered
      structure, with the layers being separated by solvent of crystallization
      (dimethyl sulfoxide) molecules. All the complexes have been characterized by
      single-crystal X-ray diffraction studies. Complexes 1b, 2a, and 2b crystallize in
      a monoclinic lattice, but 1a adopts a tetragonal lattice. The unit cell
      dimensions are, for 1a, a = 8.095(1) A, b = 8.095(1) A, c = 46.283 (6) A, alpha =
      90 degrees, beta = 90 degrees, and gamma = 90 degrees (space group P4(3)2(1)2, Z
      = 4), for 1b, a = 22.774(2) A, b = 11.375 (1) A, c = 22.533(2) A, alpha = 90
      degrees, beta = 104.15(1) degrees, and gamma = 90 degrees (space group P2(1)/c, Z
      = 4), for 2a, a = 17.657(6) A, b = 18.709(4) A, c = 21.044(6) A, alpha = 90
      degrees, beta = 108.68(3) degrees, and gamma = 90 degrees (space group, C2/c, Z =
      8), and, for 2b, a = 11.025(5) A, b = 15.139(4) A, c = 11.443(4) A, alpha = 90
      degrees, beta = 97.48(3) degrees, and gamma = 90 degrees (space group P2/n, Z =
      2). In all the complexes 1a, 1b, 2a, and 2b, the basic interaction between Co(II)
      and 4,4'-bipyridine remains the same with the formation of linear Co-N dative
      bonds, but the carboxylates display various modes of interaction with Co(II). The
      average Co-N and Co-O distances are 2.161 and 2.108 A, respectively.

PMID- 14731008
TI  - Toward a computational description of nitrile hydratase: studies of the ground
      state bonding and spin-dependent energetics of mononuclear, non-heme Fe(III)
      complexes.
AB  - The metal coordination and spin state of the Fe(III) center in nitrile hydratase
      (NHase) has stimulated the synthesis of model complexes in efforts to understand
      the reactivity and spectroscopic properties of the enzyme. We report density
      functional theory (DFT) calculations on a number of Fe(III) complexes that have
      been prepared as models of the NHase metal center, together with others having
      similar ligands but different ground state spin multiplicities. Our results
      suggest that a DFT description of specific spin configurations in these systems
      does not suffer from significant amounts of spin contamination. In particular,
      B3LYP calculations not only reproduce the observed spin state preferences of
      these Fe(III) complexes but also predict spin-dependent structural properties
      consistent with those expected on the basis of ligand field models. An analysis
      of the natural bond orbital (NBO) transformation of the Kohn-Sham wave functions
      has enabled quantitation of the overall contribution to covalency of ligand-to
      metal sigma-donation and pi-donation, and metal-to-ligand pi-back-bonding in
      these Fe(III) complexes at their BLYP-optimized geometries. Although sulfur
      ligands are the primary source of covalency in the Fe(III) complexes, our
      quantitative analysis suggests that hyperbonding between metal-bound nitrogens
      and an Fe-S bond represents a mechanism by which Fe-N covalency may arise. These
      studies establish the computational methodology for future theoretical
      investigations of the NHase Fe(III) center.

PMID- 14731009
TI  - Coordination frameworks containing the pyrimidin-4-olate ligand. Synthesis,
      thermal, magnetic, and ab initio XRPD structural characterization of nickel and
      zinc derivatives.
AB  - Extended coordination frameworks containing the pyrimidin-4-olate ligand (4-pymo)
      and Zn(II) and Ni(II) metal ions have been obtained by solid state reactions and
      have been fully characterized by spectroscopic, thermal, and magnetic
      measurements and by ab initio XRPD. The reaction of ZnO and 4-Hpymo at 140
      degrees C gives a solid microcrystalline phase, Zn(4-pymo)(2) (1). Its 3D
      framework contains Zn(II) centers linked by 4-pymo ligands acting in two
      different coordination modes, namely, the N,N'- and the N,O-exo-bidentate ones,
      which result in a pseudotetrahedral ZnN(3)O chromophore. Thermal treatment of the
      "molecular" Ni(4-pymo)(2)(H(2)O)(4) complex (2) above 140 degrees C gives an
      anhydrous amorphous material analyzing as Ni(4-pymo)(2) (3a). Further heating of
      this material above 388 degrees C results in the formation of the
      microcrystalline layered Ni(4-pymo)(2) species (3b), in which Ni(II) centers are
      bridged by N,O-exo-bidentate 4-pymo ligands (assisted by longer Ni.N contacts).
      The thermal dependence of the magnetic susceptibility has been studied for the
      paramagnetic species 2 and 3a. 2 shows a weak antiferromagnetic interaction [J = 
      0.313(5) cm(-)(1)] transmitted through the multiple H-bonding interactions
      between the exocyclic pyrimidine and water oxygen atoms coordinated to the metal
      centers. 3a behaves as a 2D Heisenberg antiferromagnet with J = -4.11(3) cm(
      )(1).

PMID- 14731010
TI  - Photochromism of metal complexes composed of diarylethene ligands and Zn(II),
      Mn(II), and Cu(II) hexafluoroacetylacetonates.
AB  - Metal complexes composed of bidentate 1,2-bis(2-methyl-5-(4-pyridyl)-3
      thienyl)perfluorocyclopentene (1a) and monodentate 1-(2-methyl-5-phenyl-3
      thienyl)-2-(2-methyl-5-(4-pyridyl)-3-thienyl)perfluorocyclopentene (2a)
      photochromic ligands and M(hfac)(2) (M = Zn(II), Mn(II), and Cu(II)) were
      prepared, and their photoinduced coordination structural changes were studied. X
      ray crystallographic analyses showed the formation of coordination polymers and
      discrete 1:2 complexes for bidentate and monodentate ligands, respectively. The
      complexes underwent reversible photochromic reactions by alternate irradiation
      with UV and visible lights in solution as well as in the single-crystalline
      phase. Upon photoirradiation with UV and visible light, the ESR spectra of the
      copper complexes of 1a reversibly changed. While the open-ring isomer gave an
      axial-type spectrum, the photogenerated closed-ring isomer showed a rhombic-type
      spectrum. This indicates that the photoisomerization induced the change in the
      coordination structure.

PMID- 14731011
TI  - Rearrangement reactions of the transient lewis acids (CF(3))(3)B and
      (CF(3))(3)BCF(2): an experimental and theoretical study.
AB  - Short-lived (CF(3))(3)B and (CF(3))(3)BCF(2) are generated as intermediates by
      thermal dissociation of (CF(3))(3)BCO and F(-) abstraction from the weak
      coordinating anion [B(CF(3))(4)](-), respectively. Both Lewis acids cannot be
      detected because of their instability with respect to rearrangement reactions at
      the B-C-F moiety. A cascade of 1,2-fluorine shifts to boron followed by
      perfluoroalkyl group migrations and also difluorocarbene transfer reactions
      occur. In the gas phase, (CF(3))(3)B rearranges to a mixture of linear
      perfluoroalkyldifluoroboranes C(n)()F(2)(n)()(+1)BF(2) (n = 2-7), while the
      respective reactions of (CF(3))(3)BCF(2) result in a mixture of linear (n = 2-4)
      and branched monoperfluoroalkyldifluoroboranes, e.g., (C(2)F(5))(CF(3))FCBF(2).
      For comparison, the reactions of [CF(3)BF(3)](-) and [C(2)F(5)BF(3)](-) with
      AsF(5) are studied, and the products in the case of [CF(3)BF(3)](-) are BF(3) and
      C(2)F(5)BF(2) whereas in the case of [C(2)F(5)BF(3)](-), C(2)F(5)BF(2) is the
      sole product. In contrast to reports in the literature, it is found that
      CF(3)BF(2) is too unstable at room temperature to be detected. The decomposition
      of (CF(3))(3)BCO in anhydrous HF leads to a mixture of the new conjugate Bronsted
      Lewis acids [H(2)F][(CF(3))(3)BF] and [H(2)F][C(2)F(5)BF(3)]. All reactions are
      modeled by density functional calculations. The energy barriers of the transition
      states are low in agreement with the experimental results that (CF(3))(3)B and
      (CF(3))(3)BCF(2) are short-lived intermediates. Since CF(2) complexes are key
      intermediates in the rearrangement reactions of (CF(3))(3)B and (CF(3))(3)BCF(2),
      CF(2) affinities of some perfluoroalkylfluoroboranes are presented. CF(2)
      affinities are compared to CO and F(-) affinities of selected boranes showing a
      trend in Lewis acidity, and its influence on the stability of the complexes is
      discussed. Fluoride ion affinities are calculated for a variety of different
      fluoroboranes, including perfluorocarboranes, and compared to those of the title
      compounds.

PMID- 14731012
TI  - EPR and magnetic properties of heteronuclear Mn(n)Mg(6-)(n)(O(2)CNEt(2))(12):
      impact of structural distortions on Mn(II) in weak ligand fields.
AB  - The reaction between Mn(6)L(12) and Mg(6)L(12) (L = N,N-diethylcarbamate) results
      in isolation of heteronuclear complexes Mn(n)Mg(6)(-)(n)L(12). A series was
      prepared with different doping factors n by varying the Mn/Mg ratio in the
      crystallization solutions. Single-crystal X-ray diffraction shows that
      MnMg(5)L(12) is isostructural with Mn(6)L(12) and Mg(6)L(12). Magnetic
      susceptibility data on the series Mn(n)Mg(6)(-)(n)L(12) (n = 1-6) are consistent
      with antiferromagnetic Mn.Mn interactions. At low n, the magnetic data
      demonstrate the formation of magnetically isolated Mn(2+) centers. This was
      confirmed by measurement of the EPR spectrum at a doping factor n = 0.06 in
      solution, as a powder, and as single crystals. These show hyperfine interactions
      consistent with isolated Mn(2+). The EPR spectrum of Mn(0.06)Mg(5.94)L(12)
      exhibits a dominant signal at g(eff) = 4, and a wide series of less intense
      signals spanning 200-6000 G in the X-band regime. This unusual behavior in a weak
      field Mn(2+) complex is attributed to the substantial distortions from cubic
      ligand field geometry in this system. The g(eff) = 4 signals are attributed to a
      C(2)-symmetric hexacoordinate Mn(2+) ion with D > 0.3 cm(-)(1) and E/D = 0.33.
      The wide series is assigned to an axial C(4)(v) pentacoordinate Mn(2+) site with
      D = 0.05 cm(-)(1). Comparison of the g(eff) = 4 signals to the g = 4.1 signals
      exhibited by the tetramanganese complex in photosystem II belies the fact that
      they almost certainly arise from different spin systems. In addition, the
      similarity of the spectrum of Mn(n)Mg(6)(-)(n)L(12) to mononuclear Mn(4+)
      complexes suggests that considerable care must be exercised in the use of EPR as
      a fingerprint for the manganese oxidation state, particularly in manganese
      proteins where molecular composition may not be precisely established.

PMID- 14731013
TI  - Supramolecular recognition of heteropairs of lanthanide ions: a step toward self
      assembled bifunctional probes.
AB  - Three unsymmetrical ditopic hexadentate ligands coded for the recognition of
      trivalent lanthanide ions have been synthesized, L(AB), L(AC), and L(BC), where A
      represents a benzimidazole-pyridine-benzimidazole coordination unit, B a
      benzimidazole-pyridine-carboxamide one, and C a benzimidazole-pyridine-carboxylic
      acid moiety. Under stoichiometric 2:3 (Ln:L) conditions, these ligands self
      assemble with lanthanide ions to yield triple-stranded bimetallic helicates
      having a sizable stability in acetonitrile: log beta(23) values for Eu are equal
      to 23.9 +/- 0.5 (L(AB)), 23.3 +/- 0.7 (deprotonated L(AC)), and 29.8 +/- 0.5
      (deprotonated L(BC)). The crystal structure of the EuEu helicate with L(AB) shows
      9-coordinate metal ions and an HHH (H stands for head) configuration of the
      helically wrapped ligand strands. In the presence of equimolar quantities of Ln
      and Ln' ions, L(AB) displays a remarkable predisposition to form HHH
      heterobimetallic edifices, as proved both in the solid state by the crystal
      structures of the LaEu, LaTb, PrEr, and PrLu helicates and in solution by NMR
      spectroscopy. In all cases, the benzimidazole-pyridine-carboxamide units of the
      three ligands are bound to the smaller lanthanide ion, a fact further ascertained
      by high-resolution luminescence data on LaEu and by (1)H NMR. Analysis of the
      lanthanide-induced (1)H NMR shifts and of the spin-lattice relaxation times of
      the [LnLu(L(AB))(3)](6+) series (Ln = Ce, Pr, Nd, Sm, Eu) demonstrates the
      isostructural nature of the complexes in solution and that the crystal structure
      of LaTb is a good model for the solution structure. The selectivity of L(AB) for
      heteropairs of Ln(III) ions increases with increasing difference in ionic radius,
      resulting in 70% of the heterobimetallic species for deltar(i) = 0.1 A and up to
      90% for LaLu (deltar(i) = 0.18 A), and corresponding to delta(deltaG) in the
      range 3-10 kJ.mol(-)(1). The origins of this stabilization are discussed in terms
      of the donor properties of the coordinating units and of the preferential
      formation of HHH isomers.

PMID- 14731014
TI  - A new totally flat N(sp(2))C(sp(2))N(sp(2)) pincer palladacycle: synthesis and
      photoluminescent properties.
AB  - The Sonogashira coupling of 2-bromopyridine with 8-quinolinyl-acetylene affords 2
      pyridinyl-8-quinolinyl-acetylene (1) in high yields. The chloropalladation of 1
      with Li(2)PdCl(4) in methanol at room temperature affords the pincer palladacycle
      (C(5)H(4)N-2-C=C(Cl)-8-C(9)H(6)kappaN,kappaC,kappaN)PdCl (2) in 63% yield. The X
      ray molecular structure of (2) shows that it is totally flat and that it is
      associated in pairs though pi-stacking between alternate pyridine-quinoline
      moieties (3.448 A). The pairs are also connected by pi-stacking with an interpair
      distance of 3.452 A between quinoline-quinoline moieties. A very low fluorescence
      emission was also revealed by the pincer palladacycle 2 in both solution and the
      solid state, which has been ascribed to an excimeric emission due to the
      particular structure (rigid and totally flat) of 2 in the solid state.

PMID- 14731015
TI  - Supramolecular structural variations with changes in anion and solvent in
      silver(I) complexes of a semirigid, bitopic tris(pyrazolyl)methane ligand.
AB  - The bitopic ligand p-C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2) (pz = pyrazolyl ring) that
      contains two tris(pyrazolyl)methane units connected by a semirigid organic spacer
      reacts with silver(I) salts to yield [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgX)(2)]( infinity ), where X = CF(3)SO(3)(-)
      (1), SbF(6)(-) (2), PF(6)(-) (3), BF(4)(-) (4), and NO(3)(-) (5). Crystallization
      of the first three compounds from acetone yields [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgCF(3)SO(3))(2)]( infinity ) (1a), [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgSbF(6))(2)[(CH(3))(2)CO](2)]( infinity ) (2b),
      and [p-C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)AgPF(6)]( infinity ) (3a), where the
      stoichiometry for the latter compound has changed from a metal:ligand ratio of
      2:1 to 1:1. The structure of 1a is based on helical argentachains constructed by
      a kappa(2)-kappa(1) coordination to silver of the tris(pyrazolyl)methane units.
      These chains are organized into a tubular 3D structure by cylindrical
      [(CF(3)SO(3))(6)](6)(-) clusters that form weak C-H...O hydrogen bonds with the
      bitopic ligand. The same kappa(2)-kappa(1) coordination is present in the
      structure of 2a, but the structure is organized by six different
      tris(pyrazolyl)methane units from six ligands bonding with six silvers to form a
      36-member argentamacrocycle core. The cores are organized in a tubular array by
      the organic spacers where each pair of macrocycles sandwich six acetone molecules
      and one SbF(6)(-) counterion. The structure of 3a is based on a kappa(2)-kappa(0)
      coordination mode of each tris(pyrazolyl)methane unit forming a helical
      coordination polymer, with two strands organized in a double stranded helical
      structure by a series of C-H...pi interactions between the central arene rings.
      Crystallization of 2-4 from acetonitrile yields complexes of the formula [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)[(AgX)(2)(CH(3)CN)(n)]]( infinity ) where n = 2
      for X = SbF(6)(-) (2b), X = PF(6)(-) (3b) and n = 1 for X = BF(4)(-) (4b). All
      three structures contain argentachains formed by a kappa(2)-kappa(1) coordination
      mode of the tris(pyrazolyl)methane units linked by the organic spacer and
      arranged in a 2D sheet structure with the anions sandwiched between the sheets.
      Crystallization of 5 from acetonitrile yields crystals of the formula [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgNO(3))(2)(CH(3)CN)(4)]( infinity ), where the
      nitrate is bonded to the silver. The argentachains, again formed by kappa(2)
      kappa(1) coordination, are arranged in W-shaped sheets that have an overall
      configuration very different from 2b-4b. Treating [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgSbF(6))(2)]( infinity ) with a saturated
      aqueous solution of KPF(6) or KO(3)SCF(3) slowly leads to complete exchange of
      the anion. Crystallization of a sample that contains an approximately equal
      mixture of SbF(6)(-)/PF(6)(-) from acetonitrile yields [p
      C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)[Ag(2)(PF(6))(0.78(1))(SbF(6))(1.22(1))(CH(3)CN)(
      )][(CH(3)CN)(0.25) (C(4)H(10)O)(0.25)]]( infinity ), a compound with a sheet
      structure analogous to 2b-4b. Crystallization of the same mixture from acetone
      yields [p-C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)(AgSbF(6))[(CH(3))(2)CO](1.5)](
      infinity ), where the metal-to-ligand ratio is 1:1 and the [C(pz)(3)] units are
      kappa(2)-kappa(0) bonded forming a coordination polymer. The supramolecular
      structures of all species are organized by a combination of C-H...pi, pi-pi, or
      weak C-H-F(O) hydrogen bonding interactions.

PMID- 14731016
TI  - Neutron diffraction study of [H(4)Co(4)(C(5)Me(4)Et)(4)], a tetrahedral metal
      cluster complex with four face-bridging hydride ligands.
AB  - A single-crystal neutron diffraction analysis of the cluster complex
      [H(4)Co(4)(C(5)Me(4)Et)(4)] was carried out on the new quasi-Laue diffractometer
      VIVALDI at the Institut Laue-Langevin. The structure consists of four face
      bridging hydrides attached to a tetrahedral cobalt metal core. Average distances
      and angles in the core of the molecule are as follows: Co-Co = 2.571(8), Co-C =
      2.158(6), Co-H = 1.749(7), H.H = 2.366(9) A; Co-H-Co = 94.6(3), H-Co-H = 85.1(3)
      degrees. The hydride ligands are located off the Co-Co-Co planes by an average
      distance of 0.923(8) A. It is suggested that the dimensions of the HCo(3)
      fragments found in this molecule provide reasonable estimates for analogous
      distances and angles associated with chemisorbed H atoms situated on the 3-fold
      hollows of a cobalt surface. Crystallographic details: space group P2(1)/a
      (monoclinic); a = 21.979(2), b = 10.924(1), c = 34.406(2) A; beta = 90.81(1)
      degrees; Z = 8. Final agreement factor: R(F) = 0.099 for 3779 reflections [I >
      2sigma(I)] collected at 20 K.

PMID- 14731017
TI  - Synthesis and structural characterization of 0D vanadium borophosphate
      [Co(en)(3)](2)[V(3)P(3)BO(19)][H(2)PO(4)].4H(2)O and 1D vanadium oxides
      [Co(en)(3)][V(3)O(9)].H(2)O and [Co(dien)(2)][V(3)O(9)].H(2)O templated by cobalt
      complexes: cooperative organization of the complexes and the inorganic networks.
AB  - A 0D vanadium borophosphate [Co(en)(3)](2)[V(3)P(3)BO(19)][H(2)PO(4)].4H(2)O (1)
      and two 1D vanadium oxides [Co(en)(3)][V(3)O(9)].H(2)O (2) and
      [Co(dien)(2)][V(3)O(9)].H(2)O (3) have been synthesized hydrothermally from the
      reaction mixture of V(2)O(5)-H(3)PO(4)-H(3)BO(3)-CoCl(2)-R-H(2)O at 110 degrees C
      (R: en or dien). The complex cations Co(en)(3)(3+) and Co(dien)(2)(3+) are
      cooperatively organized in the reaction medium to play a structure-directing role
      in the formation of the inorganic clusters and chains. The structures are
      determined by single-crystal X-ray diffraction analysis and further characterized
      by X-ray powder diffraction, ICP, and TG analyses. The structure of 1 contains
      isolated [V(3)P(3)BO(19)](5)(-) cluster anions, H(2)PO(4)(-) anions, racemic
      Co(en)(3)(3+) cations, and H(2)O molecules, which form a complex H-bond network.
      2 and 3 both contain chains of corner-sharing VO(4) tetrahedra running along the
      2(1) screw axis. The complex cations located in the interchain region interact
      with the chains through H-bonds. 2 is crystallized in an enantiomorphic space
      group and only one enantiomer of Co(en)(3)(3+) is involved in the structure.
      Crystal data: 1, monoclinic, C2/c, a = 32.8492(14) A, b = 11.9601(3) A, c =
      22.6001(7) A, beta = 108.9630(8) degrees, Z = 8; 2, orthorhombic, P2(1)2(1)2(1),
      a = 8.1587(16) A, b = 12.675(3) A, c = 18.046(4) A, Z = 4; 3, monoclinic,
      P2(1)/c, a = 16.1663(10) A, b = 8.7028(3) A, c = 13.9773(5) A, beta =
      103.1340(18) degrees, Z = 4.

PMID- 14731018
TI  - Molecular paramagnetic semiconductor: crystal structures and magnetic and
      conducting properties of the Ni(dmit)(2) salts of 6-oxoverdazyl radical cations
      (dmit = 1,3-dithiol-2-thione-4,5-dithiolate).
AB  - Four kinds of 1:1 and 1:3 salts of 3-[4-(trimethylammonio)phenyl]-1,5-diphenyl-6
      oxoverdazyl radical cation ([1](+)) and its mono- and dimethyl derivatives
      ([2](+) and [3](+)) with Ni(dmit)(2) anions (dmit = 1,3-dithiol-2-thione-4,5
      dithiolate) ([1](+)[Ni(dmit)(2)](-) (4), [2](+)[Ni(dmit)(2)](-) (5),
      [3](+)[Ni(dmit)(2)](-) (6), and [1](+)[Ni(dmit)(2)](3)(-) (7)) have been
      prepared, and the magnetic susceptibilities (chi(M)) have been measured between
      1.8 and 300 K. The chi(M) values of salts 5 and 7 can be well reproduced by the
      sum of the contributions from (i). a Curie-Weiss system with a Curie constant of
      0.376 (K emu)/mol and negative Weiss constants (THETAV;) of -0.4 and -1.7 K and
      (ii). a dimer system with strong negative exchange interactions of 2J/k(B) = -354
      and -258 K, respectively. The dimer formations in Ni(dmit)(2) anions have been
      ascertained by the crystal structure analyses of salts 4-6. In salts 4 and 6,
      Ni(dmit)(2) dimer molecules are sandwiched between two verdazyl cations,
      indicating the formation of a linear tetramer in 4 and 6. The magnetic
      susceptibility data for salts 4 and 6 have been fitted to a linear tetramer model
      using an end exchange interaction of 2J(1)/k(B) = -600 K and a central
      interaction of 2J(2)/k(B) = -280 K for 4 and 2J(1)/k(B) = -30 K and 2J(2)/k(B) = 
      580 K for 6, respectively. The results of the temperature dependence of the g(T)
      value in salts 4-6 obtained by ESR measurement also support the above analyses.
      The 1:1 salts 4-6 are insulators. On the other hand, the conductivity of the 1:3
      salt 7 at 20 degrees C was sigma = 0.10 S cm(-)(1) with an activation energy E(A)
      = 0.099 eV, showing the semiconductor property. Salt 7 is a new molecular
      paramagnetic semiconductor.

PMID- 14731019
TI  - Synthesis and crystal structures of a new series of intramolecular bridged
      alkylcobaloxime complexes.
AB  - A new series of intramolecular bridged alkylcobaloxime complexes were prepared by
      heating a solution of aqua-(3-bromopropyl)cobaloxime (1) through an
      intramolecular nucleophilic substitution. They are characterized by EA, ESI-MS,
      and (1)H NMR. Crystal structures of Br(O-C(3)H(6)-(dmgH))(dmgH)Co(III) (2),
      [H(2)O(O-C(3)H(6)-(dmg))(dmgH(2))Co(III)]ClO(4) (3), [Py(O-C(3)H(6)
      (dmg))(dmgH(2))Co(III)]ClO(4) (4), [Bzm(O-C(3)H(6)-(dmg))(dmgH(2))Co(III)]ClO(4)
      (5), and Im(O-C(3)H(6)-(dmg))(dmgH)Co(III) (6') were determined by X-ray
      diffraction. It is revealed that an intramolecular tri-methylene bridge exists
      between cobalt and one of the equatorial oxime oxygens forming a six-membered
      ring in the complexes. Additionally, the axial bases have some influences in
      their structure parameters, for example, Co-L bond lengths; folding angles in
      equatorial ligands; hydrogen atom positions in O-H-O bridge; and the orientations
      of those L planes with respect to the equatorial planes.

PMID- 14731020
TI  - Platinum complexes with NH groups on the carrier ligand and with only one guanine
      or hypoxanthine derivative. Informative models for assessing relative nucleobase
      and nucleotide hydrogen-bond interactions with amine ligands in solution.
AB  - Complexes of the type syn-(R,S)-Me(3)dienPtL (Me(3)dien = N,N',N' '
      trimethyldiethylenetriamine; L = guanine or hypoxanthine derivative) have two
      rotamers, a feature useful for assessing hydrogen-bond interactions between a
      Me(3)dien NH group and either the O6 or the phosphate group of the coordinated L.
      The two rotamers are defined as endo and exo for the rotamer with the six
      membered ring of the purine on the same side and on the opposite side,
      respectively, of the coordination plane as the N-Me's. For L = 5'-GMP and 5'-IMP
      the endo rotamer is the exclusive form (at neutral and basic pH) or is present at
      90% and more (low pH where 5'-phosphate group is protonated). A 5'-phosphate
      group can be positioned to form a direct H-bond with a Me(3)dien NH group only in
      the endo form; such an H-bond explains this high endo preference. Such a direct
      phosphate-NH H-bond is not possible for other complexes used in this study
      because either L has no phosphate group (9-EtG, Guo) or the phosphate is at the
      3'-position (3'-GMP and 3'-IMP), too far for H-bonding. Nevertheless, a
      preference for the endo rotamer was observed for these L also. This result is
      opposite to that expected both from potential steric repulsion of the L O6 with
      the N-Me groups and also from the lack of a potential favorable H-bond
      interaction between L O6 and a Me(3)dien NH. For the 9-EtG adduct, the
      temperature dependence of the endo/exo equilibrium and the activation parameters
      for endo/exo interconversion suggest that the preference for the endo rotamer
      arises from the hydration of the Me(3)dien NH groups; such hydration is favorable
      in the endo rotamer. At basic pH, N1H deprotonation increases the H-bond capacity
      of O6, and the exo rotamer increases in stability, becoming the dominant rotamer
      for the 9-EtG and Guo adducts. For L = 3'-GMP and 3'-IMP, stabilization of the
      endo form upon phosphate deprotonation at neutral pH was observed. This result is
      attributed to an H-bonding network involving water, the 3'-phosphate, and the
      Me(3)dien NH groups.

PMID- 14731021
TI  - An ab initio study on luminescent properties and aurophilic attraction of
      binuclear gold(I) complexes with phosphinothioether ligands.
AB  - Electronic structures and spectroscopic properties of the binuclear head-to-tail
      [Au(2)(PH(2)CH(2)SH)(2)](2+) (1) complex were investigated by ab initio
      calculations. The solvent effect of the complex in the acetonitrile solution was
      taken into account by the weakly solvated [Au(2)(PH(2)CH(2)SH)(2)](2+).(MeCN)(2)
      (2) moiety in the calculations. The ground-state geometries of 1 and 2 were fully
      optimized by the MP2 method, while their excited-state structures were optimized
      by the CIS method. Aurophilic attraction apparently exists between the two Au(I)
      atoms in the ground state and is strongly enhanced in the excited state. A high
      energy phosphorescent emission was calculated at 337 nm for 1 in the absence of
      the interactions with solvent molecules and/or counteranion in solid state;
      however the lowest-energy emission of 2 was obtained at 614 nm with the nature of
      (3)A(u)(s(sigma)) --> (1)A(g)(d(sigma)) (metal-centered, MC) transition. The
      coordination of acetonitrile to the gold atom in solution results in a dramatic
      red shift of emission wavelength. The investigations on the head-to-tail
      [Au(2)(PH(2)CH(2)SCH(3))(2)](2+) (5) and
      [Au(2)(PH(2)CH(2)SCH(3))(2)](2+).(MeCN)(2) (6) moieties indicate that the CH(3)
      substituent on the S atom causes blue shifts of emission wavelength for 5 and 6
      with respect to 1 and 2. By comparison between Au(I) thioether 1 and head-to-tail
      Au(I) thiolate [Au(2)(PH(2)CH(2)S)(2)] (7), it is concluded that the S-->Au
      dative bonding results in evidently different transition characteristics from the
      S-Au covalent bonding in the Au(I) thioether/thiolate complexes.

PMID- 14731022
TI  - Adducts of acetylene and dimethylacetylenedicarboxylate at sulfurs in sulfur
      bridged incomplete cubane-type tungsten clusters.
AB  - Reactions are reported of sulfur-bridged incomplete cubane-type tungsten clusters
      having W(3)(micro(3)-S)(micro-S)(3) cores with acetylene and its derivative
      dimethylacetylenedicarboxylate (DMAD). The reaction of the isothiocyanate
      tungsten cluster [W(3)(micro(3)-S)(micro-S)(3)(NCS)(9)](5)(-) (5) with acetylene
      in 0.1 M HCl afforded a novel complex having two acetylene molecules in different
      adduct formation modes, [W(3)(micro(3)-S)(micro(3)-SCH=CHS)(micro
      SCH=CH(2))(NCS)(9)](4)(-) (6), and the presence of two kinds of intermediates
      [W(3)(micro(3)-S)(micro-S)(micro(3)-SCH=CHS)(NCS)(9)](5)(-) (7) and
      [W(3)(micro(3)-S)(micro-S)(2)(micro-SCH=CH(2))(NCS)(9)](4)(-) (8) was observed.
      The reaction of the diethyldithiophosphate (dtp) tungsten cluster [W(3)(micro(3)
      S)(micro-S)(3)(micro-OAc)(dtp)(3)(CH(3)CN)] (10) with DMAD in acetonitrile
      containing acetic acid resulted in the formation of another complex having two
      DMAD molecules of different adduct formation modes, [W(3)(micro(3)-S)(micro
      SC(CO(2))=CH(CO(2)CH(3)))(micro(3)-SC(CO(2)CH(3))=C(CO(2)CH(3))S)(micro
      OAc)(dtp)(3)] (11), where hydrolysis of one of the four ester groups of the two
      DMAD groups occurred and the resultant carboxylic group coordinated to tungsten.
      The conformation of the micro-SCH=CH(2) moiety in 6 is different from that of the
      corresponding moiety in [W(3)(micro(3)-S)(micro-O)(micro-S)(micro
      SCH=CH(2))(NCS)(9)](4)(-) (4). Introduction of the second acetylene molecule to
      the intermediate [W(3)(micro(3)-S)(micro-S)(2)(micro-SCH=CH(2))(NCS)(9)](4)(-)
      (8) resulted in the formation of 6. The clusters were characterized by UV-vis
      spectroscopy, (1)H NMR spectroscopy, and X-ray crystallography (for
      (Hpy)(4).6.1.33py.0.5H(2)O and 11.CH(3)CN), and the formation of 6 and 11 was
      examined in detail from a mechanistic point of view.

PMID- 14731023
TI  - Density functional study of a micro-1,1-carboxylate bridged Fe(III)-O-Fe(IV)
      model complex. 2. Comparison with ribonucleotide reductase intermediate X.
AB  - Using broken-symmetry density functional theory, we have studied an
      experimentally proposed model for ribonucleotide reductase (RNR) intermediate X,
      which contains a single oxo bridge, one terminal H(2)O or OH(-) ligand, a
      bidentate carboxylate from Glu115, and a mono-oxygen bridge provided by Glu238.
      For the models proposed here, the terminal H(2)O/OH(-) ligand binds to site Fe1
      which is closer to Tyr122. The diiron centers are assigned as high-spin
      Fe(III)Fe(IV) and antiferromagnetically coupled to give the S(total) = (1)/(2)
      ground state. Calculations show that the model with a terminal hydroxide in the
      antiferromagnetic [S(Fe1) = 2, S(Fe2) = (5)/(2)] state (Fe1 = Fe(IV), Fe2 =
      Fe(III)) is the lowest energy state, and the calculated isomer shift and
      quadrupole splitting values for this cluster are also the best among the four
      clusters studied here when compared with the experimental values. However, the
      DFT-calculated (1)H proton and (17)O hyperfine tensors for this state do not show
      good agreement with the experiments. The calculated Fe1-Fe2 distances for this
      and the other three clusters at >2.9 A are much longer than the 2.5 A which was
      predicted by the EXAFS measurements. The mono-oxygen bridge provided by Glu238
      tends to be closer to one of the Fe sites in all clusters studied here, and it
      does not function as a bridge in helping to produce a short Fe-Fe distance.
      Overall, the models tested here are not likely to represent the core structure of
      RNR intermediate X. The model with the terminal OH(-) binding to the Fe1(III)
      center shows the best calculated (1)H proton and (17)O hyperfine tensors compared
      with the experimental values. This supports the earlier proposal based on
      analysis of ENDOR spectra (Willems et al.(16)) that the terminal oxygen group
      binds to the Fe(III) site in RNR-X.

PMID- 14731024
TI  - Binuclear rhenium(I) complexes with bridging [2.2]paracyclophane-diimine ligands:
      probing electronic coupling through pi-pi interactions.
AB  - Two pseudo-para substituted bis-diimino[2.2]paracyclophane ligands (4,16
      bis(picolinaldimine)-[2.2]paracyclophane (BPPc) and 4,16-bis(methyl
      picolinaldimine)-[2.2]paracyclophane (BmPPc)) were prepared by the condensation
      reaction of the appropriate picolinaldimine with 4,16-diamino-[2.2]paracyclophane
      (2). An improved synthesis of 2 from [2.2]paracyclophane also is reported. BPPc
      (3a): monoclinic, P2(1)/c, a = 8.2238(11) A, b = 15.336(2) A, c = 8.4532(11) A,
      beta = 98.578(3) degrees, V = 1054.2(2) A(3), Z = 2. To investigate the binding
      properties of the bis-diimino[2.2]paracyclophane ligands, binuclear rhenium(I)
      tricarbonyl chloride complexes [Re(CO)(3)Cl](2)(micro-BPPc) (5a) and
      [Re(CO)(3)Cl](2)(micro-BmPPc) (5b) were prepared and fully characterized by
      infrared spectroscopy, (1)H NMR spectroscopy, elemental analysis, UV-visible
      absorption spectroscopy, and cyclic voltammetry. Two model complexes, Re(tolyl
      pyCa)(CO)(3)Cl (4) (tolyl-pyCa = N-(p-tolyl)-2-pyridinecarboxaldimine) and
      [Re(CO)(3)Cl](2)(micro-PBP) (6) (PBP = p-phenylenebis(picolinaldimine)), also are
      reported. The dimeric compounds 5 and 6 each undergo two one-electron,
      predominantly diimine-centered reduction processes. Spectroscopic data and
      comproportionation constants (5a, 23 +/- 9; 5b, 23 +/- 9; 6, 2750 +/- 540) are
      consistent with relatively weak interactions between the diimine groups mediated
      by the paracyclophane bridging group, and these results are consistent with
      steric and electronic factors.

PMID- 14731025
TI  - Syntheses, structures, and properties of intercalation compounds of silver(I)
      complex with [2.2]paracyclophane.
AB  - Reaction of [2.2]paracyclophane (pcp) with silver(I) trifluoroacetate
      (AgCF(3)CO(2)) and silver(I) pentafluoroproprionate (AgC(2)F(5)CO(2)) has led to
      isolation of three novel intercalation polymers:
      [Ag(4)(pcp)(CF(3)CO(2))(4)](C(6)H(6)) (1),
      [Ag(4)(pcp)(CF(3)CO(2))(4)](C(6)H(3)Me(3)) (2), and
      [Ag(4)(pcp)(C(2)F(5)CO(2))(4)](pcp) (3). Structure studies using single crystal X
      ray diffraction have shown that all compounds contain two-dimensional layered
      frameworks based on cation-pi interactions, in which pcp exhibits an
      unprecedented micro-tetra-eta(2) coordination mode. Guest molecules which weakly
      interact with the host pcp via C-H.pi interactions are intercalated between
      layers. The guest-eliminated complexes (1a and 2a) and guest-reincorporated ones
      (1b or 1c and 2b or 2c), accompanied by small structural changes, were confirmed
      by (1)H NMR, thermogravimetric analysis, mass spectra, and X-ray powder
      diffraction patterns. The structural changes from 1 --> 1a --> 1c (=1) can take
      place reversibly in the process of exposure of 1a to benzene vapor. The original
      framework of complex 2 is also completely recovered by immersing 2a in mesitylene
      as well as exposing it to mesitylene vapor.

PMID- 14731026
TI  - Generation of spirotricyclic site-differentiated cyclotriphosphazenes: a solvent
      free approach to multidentate N/O donor ligand systems.
AB  - Cyclotriphosphazene-based ligand systems are valuable materials to model the
      metal-binding event on the structurally and electronically related functionalized
      high molecular weight polyphosphazenes. We here report the facile synthesis of
      novel spirotricyclic cyclotriphosphazenes N(3)P(3)(MeNC(2)H(4)NMe)(2)L(2),
      N(3)P(3)(iPrNC(2)H(4)NiPr)(2)L(2), and N(3)P(3)(o-O(2)C(12)H(8))(2)L(2) that
      enables different substituents to be incorporated into the ligand system. This
      synthetic approach allows for control over the solubility and steric requirements
      of the exocyclic bidentate substituents, as well as the donor type and denticity
      of the coordination sites. A mononuclear lanthanum complex
      ([La(NO(3))(3)[N(3)P(3)(pzpy)(2)(MeNC(2)H(4)NMe)(2)]] (7)) and a series of
      dinuclear transition-metal complexes
      ([[ReCl(CO)(3)](2)[N(3)P(3)(pyNH)(2)(MeNC(2)H(4)NMe)(2)]] (4),
      [[FeI(2)](2)[N(3)P(3)(pyNH)(2)(MeNC(2)H(4)NMe)(2)]] (5), and
      [[PdCl(2)](2)[N(3)P(3)(pyNH)(2)(MeNC(2)H(4)NMe)(2)] (6)) have been prepared and
      structurally and spectroscopically characterized to explore the metal
      coordination environments supported by this class of ligands.

PMID- 14731027
TI  - Synthesis and spectroscopy of micro-oxo (O(2)(-))-bridged heme/non-heme diiron
      complexes: models for the active site of nitric oxide reductase.
AB  - In this paper, we describe the synthesis and study of a series of heme/non-heme
      Fe-O-Fe' complexes supported by a porphyrin and the tripodal nitrogen ligand TMPA
      [TMPA = tris(2-pyridylmethyl)amine]. The complete synthesis of [((6)L)Fe-O
      Fe(X)](+) (1) (X = OMe(-) or Cl(-), 69:31 ratio), where (6)L is the dianion of 5
      (o-O-[(N,N-bis(2-pyridylmethyl)-2-(6-methoxyl)pyridinemethanamine)phenyl]
      10,15,20-tris(2,6-difluorophenyl)porphine, is reported. The crystal structure for
      1.PF(6) reveals an intramolecular heme/non-heme diferric complex bridged by an Fe
      O-Fe' moiety; 90 degree angle (Fe-O-Fe') = 166.7(3) degrees, and d(Fe.Fe') =
      3.556 A. Crystal data for C(70)H(57)ClF(12)Fe(2)N(8)O(3)P (1.PF(6)): triclinic,
      Ponemacr;, a = 13.185(3) A, b = 14.590 (3) A, c = 16.885(4) A, alpha = 104.219(4)
      degrees, beta = 91.572(4) degrees, gamma = 107.907(4) degrees, V = 2977.3(11)
      A(3), Z = 2, T = 150(2) K. Complex 1 (where X = Cl(-)) is further characterized
      by UV-vis (lambda(max) = 328, 416 (Soret), 569 nm), (1)H NMR (delta 27-24 [TMPA 
      CH(2)-], 16.1 [pyrrole-H], 15.2-10.5 [PY-3H, PY-5H], 7.9-7.2 [m- and p-phenyl-H],
      6.9-5.8 [PY-4H] ppm), resonance Raman (nu(as)(Fe-O-Fe') 844 cm(-)(1)), and
      Mossbauer (delta(Fe) = 0.47, 0.41 mm/s; deltaE(A) = 1.59, 0.55 mm/s; 80 K)
      spectroscopies, MALDI-TOF mass spectrometry (m/z 1202), and SQUID susceptometry
      (J = - 114.82 cm(-)(1), S = 0). We have also synthesized a series of 3-, 4-, and
      5-methyl-substituted as well as selectively deuterated TMPA(Fe') complexes and
      condensed these with the hydroxo complex (F(8))FeOH or (F(8)-d(8))FeOH to yield
      "untethered" Fe-O-Fe' analogues. Along with selective deuteration of the
      methylene hydrogens in TMPA, complete (1)H NMR spectroscopic assignments for 1
      have been accomplished. The magnetic properties of several of the untethered
      complexes and a comparison to those of 1 are also presented. Complex 1 and
      related species represent good structural and spectroscopic models for the
      heme/non-heme diiron active site in the enzyme nitric oxide reductase.

PMID- 14731028
TI  - Intense fluorescence of metal-to-ligand charge transfer in [Pt(0)(binap)(2)]
      [binap = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl].
AB  - [Pt(0)(binap)(2)] (binap = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) is found
      to exhibit a luminescence from metal-to-ligand charge transfer state (MLCT) with
      a quantum yield of 0.12 and a lifetime of 1.2 micros in toluene at an ambient
      temperature. Prompt fluorescence with a quantum yield of 1.6 x 10(-)(4) is
      observed by means of a picosecond time-correlated single photon counting
      technique. The spectrum of the steady-state luminescence is almost identical to
      that of the prompt fluorescence, indicating that the intense luminescence is
      mainly delayed fluorescence from thermally activated (1)MLCT. The analysis of the
      temperature-dependent emission indicates that the energy difference between the
      (1)MLCT and (3)MLCT is 1.15 x 10(3) cm(-)(1). The lifetime of the prompt
      fluorescence is determined to be 3.2 ps from the decay of stimulated emission
      overlapped on subpicosecond transient absorption spectra. The lifetime of the
      (1)MLCT is much longer than expected from the large spin-orbit coupling constant
      of 5d (Pt) electrons (4000 cm(-)(1)). Theoretical analysis based on density
      functional theory reveals that structural distortion in the MLCT states causes
      large energy splitting between HOMO and HOMO - 1, which prevents a very fast ISC
      induced by strong spin-orbit interactions between these orbitals. The relatively
      slow ISC is therefore induced by weak spin-orbit interactions (ca. 50 cm(-)(1))
      between ligand-centered molecular orbitals. Theoretical calculations indicate
      that the phosphorescence observed at lower temperatures is due to intensity
      borrowing from 4(1)B(2) --> GS transition. However, the large energy difference
      between HOMO and HOMO - 2 reduces the extent of mixing between the lowest (3)MLCT
      and 4(1)B(2) due to spin-orbit interaction, thereby decreasing the radiative rate
      of the phosphorescence.

PMID- 14731030
TI  - Carbonyl-carboxylato-ruthenium complexes incorporating diimine ligands and
      unexpected cyclometalation of carboxylate ligands.
AB  - We report two new synthetic routes to the dinuclear Ru(I) complexes,
      [Ru(I)(2)(RCO(2))(CO)(4)(N( wedge )N)(2)](+) (N( wedge )N = 2,2'-bipyridine or
      1,10-phenanthroline derivatives) that use RuCl(3).3H(2)O as a starting material.
      Direct addition of the bidentate diimine ligand to a methanolic solution of
      [Ru(CO)(2)Cl(2)](n) and sodium acetate yielded a mixture of
      [Ru(I)(2)(MeCO(2))(CO)(4)(N( wedge )N)(2)](+) (N( wedge )N = 4,4'-dmbpy, and 5,6
      dmphen), and [Ru(II)(MeCO(2))(2)(CO)(2)(N( wedge )N)] (N( wedge )N = 4,4'-dmbpy
      and 5,5'-dmbpy). Single-crystal X-ray studies confirmed that the Ru(II) complexes
      had a trans-acetate-cis-carbonyl arrangement of the ligands. In contrast, the use
      of sodium benzoate resulted in the unexpected formation of a Ru-C bond producing
      ortho-cyclometalated complexes, [Ru(II)(O(2)CC(6)H(4))(CO)(2)(N( wedge )N)],
      where N( wedge )N = bpy or phen. A second approach used ligand exchange between a
      bidentate ligand (N( wedge )N) and the pyridine ligands of
      [Ru(I)(RCO(2))(CO)(2)(py)](2) to convert these neutral complexes into
      [Ru(I)(2)(RCO(2))(CO)(4)(N( wedge )N)(2)](+). This method, although it involved
      more steps, was applicable for a wider variety of diimine ligands (R = Me and N(
      wedge )N = 4,4'-dmbpy, 5,5'-dmbpy, 5,6-dmphen; R = Ph and N( wedge )N = bpy,
      phen, 5,6-dmphen).

PMID- 14731029
TI  - Structural conversions of molybdenum-iron-sulfur edge-bridged double cubanes and
      P(n)-type clusters topologically related to the nitrogenase P-cluster.
AB  - Edge-bridged Mo-Fe-S double cubanes are versatile precursors for the synthesis of
      other clusters of the same nuclearity. Thus, the double cubane
      [(Tp)(2)Mo(2)Fe(6)S(8)(PEt(3))(4)] sustains terminal ligand substitution with
      retention of the Mo(2)Fe(6)(micro(3)-S)(6)(micro(4)-S)(2) core structure and
      rearrangement to the Mo(2)Fe(6)(micro(2)-S)(2)(micro(3)-S)(6)(micro(6)-S)
      topology of the nitrogenase P(N) cluster upon reaction with certain nucleophiles.
      Four distinct processes for the conversion of double cubanes to P(N)-type
      clusters are documented, affording the products
      [(Tp)(2)Mo(2)Fe(6)S(9)(SR)(2)](3)(-), [(Tp)(2)Mo(2)Fe(6)S(8)(OMe)(3)](3)(-), and
      [(Tp)(2)Mo(2)Fe(6)S(7)(OMe)(4)](2)(-). In the latter clusters, two methoxides are
      terminal ligands and one or two are micro(2)-bridging ligands. The reverse
      transformation of a P(N)-type cluster to an edge-bridged double cubane has been
      demonstrated by the reaction of [(Tp)(2)Mo(2)Fe(6)S(8)(OMe)(3)](3)(-) with
      Me(3)SiX to afford [(Tp)(2)Mo(2)Fe(6)S(8)X(4)](2)(-) (X = Cl(-), Br(-)). Edge
      bridged double cubanes have been obtained in the oxidation states
      [Mo(2)Fe(6)S(8)](2+,3+,4+). The stable oxidation state of P(N)-type clusters is
      [Mo(2)Fe(6)S(9)](+). Structures of five double cubanes and four P(N)-type
      clusters are reported. The P(N)-type clusters are synthetic representations of
      the biologically unique topology of the native P(N) cluster. Best-fit
      superpositions of the native and synthetic cluster cores gives weighted rms
      deviations in atom positions of 0.20-0.38 A. This study and an earlier
      investigation (Zhang, Y.; Holm, R. H. J. Am. Chem. Soc. 2003, 125, 3910-3920)
      provide a comprehensive account of the synthesis of structural analogues of the
      native P(N) cluster and provide the basis for continuing investigation of the
      synthesis of weak-field Mo-Fe-S clusters related to nitrogenase. (Tp =
      tris(pyrazolyl)hydroborate(1-).)

PMID- 14731031
TI  - Europium(II) and ytterbium(II) cyclic organohydroborates: an europium(II) complex
      with an agostic interaction.
AB  - Lanthanide bis((cyclooctane-1,5-diyl)dihydroborate) complexes (THF)(4)Ln[(micro
      H)(2)BC(8)H(14)](2) (Ln = Eu, 1; Yb, 2) were synthesized by a metathesis reaction
      between (THF)(x)()LnCl(2) and K[H(2)BC(8)H(14)] in THF in a 1:2 molar ratio.
      Attempts to prepare the monosubstituted lanthanide cyclic organohydroborates
      (THF)(x)LnCl[(micro-H)(2)BC(8)H(14)] were unsuccessful. On the basis of the
      molecular structure and IR spectrum of 1, there is an agostic interaction between
      Eu(II) and one of the alpha-C-H hydrogens from the [(micro-H)(2)BC(8)H(14)] unit.
      No such interaction was observed for 2. The coordinated THF in 1 and 2 can be
      removed under dynamic vacuum, but the solvent ligands remain bound to Yb when 2
      is directly dissolved in Et(2)O or toluene. In strong Lewis basic solvents, such
      as pyridine or CH(3)CN, attack of the Yb-H-B bridge bonds results. Decomposition
      of 2 to the 9-BBN dimer in CD(2)Cl(2) was observed by (11)B and (1)H NMR
      spectroscopies. Compound 2 was reacted with 2 equiv of the hydride ion
      abstracting reagent B(C(6)F(5))(3) to afford the solvent-separated ion pair
      [Yb(THF)(6)][HB(C(6)F(5))(3)](2) (3). Complexes 1, 2, and 3 were characterized by
      single-crystal X-ray diffraction analysis. Crystal data: 1 is orthorhombic,
      Pna2(1), a = 21.975(1) A, b = 9.310(1) A, c = 16.816(1) A, Z = 4; 2 is triclinic,
      P1, a = 9.862(1) A, b = 10.227(1) A, c = 10.476(1) A, alpha = 69.87(1) degrees,
      beta = 76.63(1) degrees, gamma = 66.12(1) degrees, Z = 1; 3.Et(2)O is triclinic,
      P1, a = 13.708(1) A, b = 14.946(1) A, c = 17.177(1) A, alpha = 81.01(1) degrees,
      beta = 88.32(1) degrees, gamma = 88.54(1) degrees, Z = 2.

PMID- 14731032
TI  - [Mg(XeF(2))(n)()](AsF(6))(2) (n = 4, 2): first compounds of magnesium with
      XeF(2).
AB  - The reaction between Mg(AsF(6))(2) and XeF(2) in anhydrous HF (aHF) at room
      temperature yields two compounds with XeF(2) bonded directly to the Mg(2+)
      cation: [Mg(XeF(2))(4)](AsF(6))(2); [Mg(XeF(2))(2)](AsF(6))(2). The 1:4 compound
      is obtained with excess XeF(2) while the 1:2 compound is prepared from
      stoichiometric amounts of Mg(AsF(6))(2) and XeF(2). [Mg(XeF(2))(4)](AsF(6))(2)
      crystallizes in an orthorhombic crystal system, space group P2(1)2(1)2(1), with a
      = 8.698(15) A, b = 14.517(15) A, c = 15.344(16) A, V = 1937(4) A(3), and Z = 4.
      The octahedral coordination sphere of Mg consists of one fluorine atom from each
      of the four XeF(2) molecules and two fluorine atoms from the two AsF(6) units.
      [Mg(XeF(2))(2)](AsF(6))(2) crystallizes in the orthorhombic crystal system, space
      group Pbam, with a = 8.9767(10) A, b = 15.1687(18) A, c = 5.3202(6) A, V =
      724.42(14) A(3), and Z = 2. The octahedral coordination sphere consists of two
      fluorine atoms, one from each of the two XeF(2) molecules and four fluorine atoms
      from the four bridging AsF(6) units.

PMID- 14731033
TI  - Iridium(III) complexes formed by O-H and/Or C-H activation of 2-(arylazo)phenols.
AB  - Reaction of 2-(arylazo)phenols with [Ir(PPh(3))(3)Cl] in refluxing ethanol in the
      presence of a base (NEt(3)) affords complexes of three different types, viz.
      [Ir(PPh(3))(2)(NO-R)(H)Cl] (R = OCH(3), CH(3), H, Cl and NO(2)),
      [Ir(PPh(3))(2)(NO-R)(H)(2)] and [Ir(PPh(3))(2)(CNO-R)(H)]. Structures of the
      [Ir(PPh(3))(2)(NO-Cl)(H)Cl], [Ir(PPh(3))(2)(NO-Cl)(H)(2)] and [Ir(PPh(3))(2)(CNO
      Cl)(H)] complexes have been determined by X-ray crystallography. In the
      [Ir(PPh(3))(2)(NO-R)(H)Cl] and [Ir(PPh(3))(2)(NO-R)(H)(2)] complexes, the 2
      (arylazo)phenolate ligands are coordinated to the metal center as monoanionic
      bidentate N,O-donors, whereas in the [Ir(PPh(3))(2)(CNO-R)(H)] complexes, they
      are coordinated to iridium as dianionic tridentate C,N,O-donors. In all three
      products formed in ethanol, the two PPh(3) ligands are trans. Reaction of 2
      (arylazo)phenols with [Ir(PPh(3))(3)Cl] in refluxing toluene in the presence of
      NEt(3) affords complexes of two types, viz. [Ir(PPh(3))(2)(CNO-R)(H)] and
      [Ir(PPh(3))(2)(CNO-R)Cl]. Structure of the [Ir(PPh(3))(2)(CNO-Cl)Cl] complex has
      been determined by X-ray crystallography, and the 2-(arylazo)phenolate ligand is
      coordinated to the metal center as a dianionic tridentate C,N,O-donor and the two
      PPh(3) ligands are cis. All of the iridium(III) complexes show intense MLCT
      transitions in the visible region. Cyclic voltammetry shows an Ir(III)-Ir(IV)
      oxidation on the positive side of SCE and an Ir(III)-Ir(II) reduction on the
      negative side for all of the products.

PMID- 14731034
TI  - Three olefin copper(I) dimeric complexes with 2-, 3-, and 4-pyridylacrylic acid
      and their electrochemical properties.
AB  - UV irradiation of 2-, 3-, or 4-pyridylacrylic acid (2-, 3-, and 4-HPYA) with
      Cu(I)Cl at 230 nm in 4 N HCl for 1 week and subsequent hydrothermal reactions
      yielded three novel highly stable 3-D copper(I)-olefin dimers, [(2
      H(2)PYA)(2)Cu(+)(2)Cl(4)](n)() (1), [(3-H(2)PYA)(2)Cu(+)(2)Cl(4)](n)() (2), and
      [(4-H(2)PYA)(2)Cu(+)(2)Cl(4)(I)](n)() (3), respectively, in which H-bonds play a
      key role in the stabilization of supramolecular Cu(I)-olefin system and thus the
      formation of the 3-D networks. The electrochemical properties of 1-3 are also
      reported.

PMID- 14731035
TI  - A new route to chelating bis(aryloxide) ligands and their applications to
      tantalum and titanium organometallic compounds.
AB  - A new route to sterically tuned, chelating bis(aryloxide) ligands is described
      and demonstrated by the synthesis of 2,2'-ethylenebis(6-isopropylphenol) (1,
      H(2)BIPP) and transition metal complexes of its dianion. The utility of these
      ligands in titanium and tantalum organometallic chemistry is shown in the
      alkylation of (BIPP)TiCl(2) (7) to form (BIPP)TiMe(2) (8) and
      (BIPP)Ti(CH(2)Ph)(2) (9) and in the alkylation of (BIPP)TaCl(3) (10) and its base
      adducts to form (BIPP)TaMe(3) (14) and (BIPP)Ta(CH(2)Ph)(3) (13). Structural
      comparisons of the chelating 2,2'-ethylenebis(6-isopropylphenoxide) (BIPP) ligand
      with its analogous, nonchelating bis(2,6-dialkylaryloxide) ligand set are
      examined in the X-ray diffraction studies of (BIPP)TaCl(3)(THF).THF (11.THF) and
      (BIPP)Ta(CH(2)C(6)H(5))(3) (13).

PMID- 14731036
TI  - Tuning the electronic structures of platinum(II) complexes with a cyclometalating
      aryldiamine ligand.
AB  - Triflate salts of four platinum(II) pyridyl complexes with a mer-coordinating
      tridentate pincer ligand, pip(2)NCN(-) (pip(2)NCNH = 1,3
      bis(piperidylmethyl)benzene), are reported: Pt(pip(2)NCN)(L)(+) (2, L = pyridine;
      3, L = 4-phenylpyridine; 5, L = 2,6-pyridinedimethanol) and
      [(Pt(pip(2)NCN))(2)(micro-4,4'-bipyridine)](2+) (4). The complexes have been
      fully characterized by (1)H NMR spectroscopy, elemental analysis, and X-ray
      crystallography. Compound 2(CF(3)SO(3)(-)): triclinic, P1, a = 9.7518(6) A, b =
      12.0132(8) A, c = 12.6718(9) A, alpha = 114.190(2) degrees, beta = 100.745(3)
      degrees, gamma = 103.545(2) degrees, V = 1247.95(14) A(3), Z = 2. Compound
      3(CF(3)SO(3)(-)): monoclinic, P2(1)/c, a = 15.550(2) A, b = 9.7386(11) A, c =
      18.965(3) A, beta = 92.559(7) degrees, V = 2869.1(6) A(3), Z = 4. Compound
      4(CF(3)SO(3)(-))(2).1/2(CH(3))(2)CO: monoclinic, I2/a, a = 21.3316(5) A, b =
      9.6526(2) A, c = 26.1800(6) A, beta = 96.4930(10) degrees, V = 5356.0(2) A(3), Z
      = 4. Compound 5(CF(3)SO(3)(-)).3/2CHCl(3): monoclinic, P2(1)/n, a = 17.1236(10)
      A, b = 9.3591(5) A, c = 21.3189(11) A, beta = 96.11(3) degrees, V = 3397.2(3)
      A(3), Z = 4. The accumulated data indicate that the phenyl group of pip(2)NCN(-)
      labilizes the trans pyridyl ligand. The electronic structures were investigated
      using cyclic voltammetry, as well as UV-visible absorption and emission
      spectroscopies. Red emission from 2 in rigid media originates from a lowest
      triplet ligand field excited state, whereas yellow-green emissions from 3 and 4
      originate from a lowest pyridyl ligand-centered triplet pi-pi state, indicating
      that substitution of the pyridyl ligand results in a dramatic change in the
      orbital character of the emissive state.

PMID- 14731037
TI  - Synthesis and structures of complexes demonstrating the coordinative versatility
      of the 2,4-diimino-3-phosphinopentene anion (gamma-phosphino-beta-diketiminate).
AB  - The synthesis and characterization of a 2,4-diimino-3-phosphinopentene anion
      (gamma-phosphino-beta-diketiminate) is reported and enables diversification of
      the beta-diketiminate ligand framework, which has been widely employed across the
      periodic table. Phosphines are observed to adopt the gamma-position of the ligand
      rather than the N,N' chelate. While aluminum and lithium adopt the familiar N,N'
      chelate arrangement with the new 2,4-diimino-3-phosphinopentene anion ligand,
      reactions with AsCl(3) or SbCl(3) result in substitution at the beta-methyl
      position on the ligand backbone, realizing novel P-->E (E = As or Sb)
      intramolecular coordination. The chemistry of the 2,4-diimino-3-phosphinopentene
      anion can be monitored by the (31)P NMR chemical shifts, which are distinctively
      diagnostic of the coordinative engagement of the ligand.

PMID- 14731038
TI  - Hyperfine splittings in spin-frustrated trinuclear Cu(3) clusters.
AB  - The hyperfine structures of the EPR spectra of the spin-frustrated and distorted
      Cu(II) trimers were calculated in the spin-coupling model. The correlations
      between the hyperfine structures of the EPR spectra and geometry of the Cu(3)
      clusters (equilateral, isosceles, and scalene triangles) were found. For the EPR
      spectrum of the spin-frustrated ground state 2(S = 1/2) of an equilateral
      triangle Cu(3) cluster (J(12) = J(13) = J(23) = J), the calculated hyperfine
      structure represents the complicated spectrum of the 24 hyperfine lines, of total
      length 5a, where a is the hyperfine constant of the mononuclear Cu center. For an
      isosceles Cu(3) cluster (J(12) not equal J(13) = J(23)), the hyperfine splittings
      of the EPR spectra of the two split S = 1/2 levels with intermediate spins S(12)
      = 0 and S(12) = 1 are essentially different. The EPR signal of the |(S(12) = 0)S
      = 1/2> level is characterized by the four equally spaced hyperfine lines
      (interval A = a) with the same relative spectral amplitudes 16:16:16:16 and total
      length 3a. For the |(S(12) = 1)S = 1/2> level, the calculated hyperfine structure
      represents the spectrum of the 16 hyperfine lines with equal spacing (interval A'
      = a/3), the spectral intensity distribution 1:1:3:3:5:5:7:7:7:7:5:5:3:3:1:1 and
      total length 5a. These hyperfine spectra differ from the hyperfine structure (10
      lines with interval a/3) of the EPR signals of the excited S = 3/2 level of the
      Cu(3) cluster. The quartet hyperfine structure, characteristic of a single Cu(2+)
      nucleus, which was observed experimentally for the doublet ground state of the
      spin-frustrated Cu(3)(II) clusters, corresponds to the hyperfine structure of the
      EPR signal of the |(S(12) = 0)S = 1/2> level. This hyperfine structure is
      evidence of the lowering of the Cu(3) cluster symmetry from trigonal to
      orthorhombic and the small splitting of the spin-frustrated 2(S = 1/2) ground
      state.

PMID- 14731039
TI  - Does alpha-fluorination affect the structural trans-influence and kinetic trans
      effect of an alkyl ligand? Molecular structures of Pd(TMEDA)(CH(3))(R(F)) and a
      kinetic study of the trans to cis isomerization of Pt(TMEDA)(CH(3))(2)I(R(F))
      [R(F) = CF(2)CF(3), CFHCF(3), CH(2)CF(3)].
AB  - Reaction of Pd(TMEDA)(CH(3))(2) [TMEDA = tetramethylethylenediamine] with
      fluoroalkyl iodides R(F)I affords a series of square planar Pd(II) complexes
      Pd(TMEDA)(CH(3))(R(F)) [R(F) = CF(2)CF(3) (9), CFHCF(3) (10), CH(2)CF(3) (11)],
      presumably by oxidative addition followed by reductive elimination of CH(3)I. The
      solid-state structures of each compound have been determined by single crystal X
      ray diffraction studies, allowing the effect of increasing alpha-fluorination on
      the structural trans-influence of alkyl ligands to be examined. In these
      compounds there is no significant difference observed in the trans-influence of
      the three fluorinated alkyl ligands toward the trans-N atom, although a
      significant cis-influence on the neighboring methyl ligand is apparent. Oxidative
      addition of the same series of fluoroalkyl ligands to the corresponding
      Pt(TMEDA)(CH(3))(2) affords octahedral Pt(IV) complexes trans
      Pt(TMEDA)(CH(3))(2)(R(F))I [R(F) = CF(2)CF(3) (12), CFHCF(3) (13), CH(2)CF(3)
      (14)] as the kinetic products. In each case, subsequent isomerization to the
      corresponding all cis-isomers is observed; in the case of 13, the stereocenter at
      the alpha-carbon results in two diastereomeric cis-isomers, which are formed at
      different rates. The molecular structures of 13 and its more stable all cis
      isomer 16b have been crystallographically determined. Kinetic studies of the
      trans-cis isomerization reactions show the mechanism to involve a polar
      transition state, presumably involving iodide dissociation, followed by
      rearrangement of the cation, and iodide recombination. High dielectric solvents
      increase the rate, but solvent coordinating ability has no effect. Dissolved
      salts (LiI, LiOTf) show normal accelerative salt effects, with no inhibition in
      the case of added iodide, consistent with the formation of an intimate ion pair
      intermediate. The kinetic parameters show that the trans-effects of fluoroalkyl
      ligands in these compounds follow the order expected from the relative sigma
      donor properties of the ligands, with CF(2)CF(3) < CFHCF(3) < CH(2)CF(3).

PMID- 14731040
TI  - Structural, NMR, and EPR studies of S = (1)/(2) and S = (3)/(2) Fe(III) bis(4
      cyanopyridine) complexes of dodecasubstituted porphyrins.
AB  - The NMR and EPR spectra for three complexes, iron(III)
      octamethyltetraphenylporphyrin bis(4-cyanopyridine) perchlorate, [FeOMTPP(4
      CNPy)(2)]ClO(4), and its octaethyl- and tetra-beta,beta'
      tetramethylenetetraphenylporphyrin analogues, [FeOETPP(4-CNPy)(2)]ClO(4) and
      [FeTC(6)TPP(4-CNPy)(2)]ClO(4), are presented. The crystal structures of two
      different forms of [FeOETPP(4-CNPy)(2)]ClO(4) and one form of [FeOMTPP(4
      CNPy)(2)]ClO(4) are also reported. Attempts to crystallize [FeTC(6)TPP(4
      CNPy)(2)]ClO(4) were not successful. The crystal structure of [FeOMTPP(4
      CNPy)(2)]ClO(4) reveals a saddled porphyrin core, a small dihedral angle between
      the axial ligand planes, 64.3 degrees, and an unusually large tilt angle (24.4
      degrees ) of one of the axial 4-cyanopyridine ligands with respect to the normal
      to the porphyrin mean plane. There are 4 and 2 independent molecules in the
      asymmetric units of [FeOETPP(4-CNPy)(2)]ClO(4) crystallized from
      CD(2)Cl(2)/dodecane (1-4) and CDCl(3)/cyclohexane (5-6), respectively. The
      geometries of the porphyrin cores in 1-6 vary from purely saddled to saddled with
      15% ruffling admixture. In all structures, the Fe-N(p) distances (1.958-1.976 A)
      are very short due to strong nonplanar distortion of the porphyrin cores, while
      the Fe-N(ax) distances are relatively long ( approximately 2.2 A) compared to the
      same distances in S = (1)/(2) bis(pyridine)iron(III) porphyrin complexes. An
      axial EPR signal is observed (g( perpendicular ) = 2.49, g( parallel ) = 1.6) in
      frozen solutions of both [FeOMTPP(4-CNPy)(2)]ClO(4) and [FeTC(6)TPP(4
      CNPy)(2)]ClO(4) at 4.2 K, indicative of the low spin (LS, S = (1)/(2)),
      (d(yz)d(xz))(4)(d(xy))(1) electronic ground state for these two complexes. In
      agreement with a recent publication (Ikeue, T.; Ohgo, Y.; Ongayi, O.; Vicente, M.
      G. H.; Nakamura, M. Inorg. Chem. 2003, 42, 5560-5571), the EPR spectra of
      [FeOETPP(4-CNPy)(2)]ClO(4) are typical of the S = (3)/(2) state, with g values of
      5.21, 4.25, and 2.07. A small amount of LS species with g = 3.03 is also present.
      However, distinct from previous conclusions, large negative phenyl-H shift
      differences delta(m) - delta(o) and delta(m) - delta(p) in the (1)H NMR spectra
      indicate significant negative spin density at the meso-carbons, and the larger
      than expected positive average CH(2) shifts are also consistent with a
      significant population of the S = 2 Fe(II), S = (1)/(2) porphyrin pi-cation
      radical state, with antiferromagnetic coupling between the metal and porphyrin
      unpaired electrons. This is the first example of this type of porphyrin-to-metal
      electron transfer to produce a partial or complete porphyrinate radical state,
      with antiferromagnetic coupling between metal and macrocycle unpaired electrons
      in an iron porphyrinate. The kinetics of ring inversion were studied for the
      [FeOETPP(4-CNPy)(2)]ClO(4) complex using NOESY/EXSY techniques and for the
      [FeTC(6)TPP(4-CNPy)(2)]ClO(4) complex using DNMR techniques. For the former, the
      free energy of activation, deltaG, and rate of ring inversion in CD(2)Cl(2)
      extrapolated to 298 K are 63(2) kJ mol(-)(1) and 59 s(-)(1), respectively, while
      for the latter the rate of ring inversion at 298 K is at least 4.4 x 10(7) s(
      )(1), which attests to the much greater flexibility of the TC(6)TPP ring. The NMR
      and EPR data are consistent with solution magnetic susceptibility measurements
      that show S = (3)/(2) in the temperature range from 320 to 180 K for [FeOETPP(4
      CNPy)(2)](+), while both [FeOMTPP(4-CNPy)(2)](+) and [FeTC(6)TPP(4-CNPy)(2)](+)
      change their spin state from S = (3)/(2) at room temperature to mainly LS (S =
      (1)/(2)) upon cooling to 180 K.

PMID- 14731041
TI  - Quantum chemical investigations and bonding analysis of iron complexes with mixed
      cyano and carbonyl ligands.
AB  - The equilibrium structures and vibrational frequencies of the iron complexes
      [Fe(CN)(x)(CO)(y)](q) (x = 0-6 and y = 0-5) have been calculated at the BP86
      level of theory. The nature of the Fe-CN and Fe-CO has been analyzed with an
      energy partitioning method. The calculated Fe-CO bond lengths are in good
      agreement with the results of X-ray structure analysis whereas the Fe-CN bonds
      are calculated somewhat longer than the experimental values. The theoretically
      predicted vibrational frequencies of the C-O stretching mode are always lower and
      the calculated CN(-) frequencies are higher than the observed fundamental modes.
      The results of the bonding analysis suggest that the Fe-CO binding interactions
      have approximately 55% electrostatic character and approximately 45% covalent
      character. There is a significant contribution of the pi orbital interaction to
      the Fe-CO covalent bonding which increases when the complexes become negatively
      charged. The strength of deltaE(pi) may even be larger than deltaE(sigma). The Fe
      CN(-) bonds have much less pi character. The calculated binding energy of the Fe
      CO pi-interactions correlates very well with the C-O stretching frequencies.

PMID- 14731042
TI  - Characterization and structure determination of ammonium bismuth oxalate hydrate,
      Bi(NH(4))(C(2)O(4))(2).xH(2)O.
AB  - From on-line coupled TGA-MS and TGA-FTIR measurements, in combination with a
      quantitative chemical analysis, it was deduced that the chemical formula for an
      unknown bismuth oxalate compound had to be Bi(NH(4))(C(2)O(4))(2).3.71(6)H(2)O.
      Solution of the crystallographic structure on the basis of X-ray powder data
      proved this formula to be correct. The diffraction pattern was indexed by a
      tetragonal unit cell [a and c respectively 11.6896(2) and 9.2357(3) A; M(20) =
      195 and F(30) = 302; Z(calc) = 4], from which the space group I4(1)/amd (No. 141)
      was derived. Direct methods were applied to solve the structure. The initial
      structural model was subsequently refined by means of the Rietveld method (R(B) =
      8.0%, R(wP) = 14.0%). Bi is 8-fold coordinated by oxygen from the oxalate anions.
      Since these BiO(8) polyhedrons do not share any edges or vertexes, an open
      framework is formed with water and ammonium molecules between. As a result, water
      can easily be removed, which is clearly indicated by the instant weight loss in
      the TGA upon heating. Moreover, as shown by HT-XRD, this process of water
      exchange is reversible as long as the heating temperature does not exceed 100
      degrees C.

PMID- 14731043
TI  - The Pd(4)(dppm)(4)(H)(2)(2+) cluster: a precatalyst for the homogeneous
      hydrogenation of alkynes.
AB  - The catalytic properties of the title cluster toward the homogeneous
      hydrogenation of phenylacetylene, diphenylethyne and phenyl-1-propyne have been
      investigated as a function of temperature, pressure, solvents, substrate and
      cluster concentrations, and counterions. The title cluster is a precatalyst that
      exhibits a good catalytic activity under mild conditions (1 atm of H(2) at 20
      degrees C) for the hydrogenation of alkynes and alkenes. For the alkyne
      substrates, the turnover frequencies (tof's) range between 200 and 500 h(-)(1),
      and the product distribution varies as: cis-products, 75-90%; trans-products; 0
      8% after 3 h of reaction. Based on the graphs -d[substrate]/dt vs [Pd(4)](1/2),
      the mechanism indicates a cluster dissociation into two dimers (presumably of the
      type Pd(2)(dppm)(2)(H)(solvent)(+)). The variations of tof (or -d[substrate]/dt)
      as a function of [substrate] and pressure of H(2) are linear. At 1600 psi of
      H(2), the tof can reach 2500-3000 h(-)(1) (in THF). The tof also increases with
      temperature reaching a maximum at approximately 35 degrees C (tof: 1000-1300 h(
      )(1)), but at higher temperatures cluster decomposition begins to occur, leading
      to a rapid decrease in rates of catalysis. At 50 degrees C, no catalysis is
      observed. The hydrogenation reaction can be stopped at the corresponding cis
      alkenes with approximately 95% yields, depending on the substrate and
      experimental conditions used. The tof's also vary with the solvent, where
      stronger coordinating solvent molecules give higher tof's. In addition, the tof's
      do not change with the nature of the counterion, which acts as "spectator" in the
      catalysis.

PMID- 14731044
TI  - Ga(2,2'-bipy)(HPO(4))(H(2)PO(4)): first layered inorganic-organic hybrid gallium
      phosphate with a neutral framework.
AB  - A novel gallium phosphate, Ga(2,2'-bipy)(HPO(4))(H(2)PO(4)) (denoted FJ-12; FJ =
      Fujian Institute of Research on the Structure of Matter), which is the first
      example of layered inorganic-organic hybrid gallium phosphate with neutral
      framework, has been hydrothermally synthesized and structurally characterized by
      single-crystal X-ray diffraction. This compound crystallizes in the monoclinic
      system, space group P2(1)/c (No. 14), with a = 10.9443(9), b = 15.8253(13), and c
      = 8.4201(7) A, beta = 108.898(2) degrees, V = 1379.7(2) A(3), and Z = 4. The
      structure consists of HPO(4) and H(2)PO(4) tetrahedra and unusual GaO(4)N(2)
      octahedra which are linked through their vertexes forming an undulated sheetlike
      structure with 4.12-net. The adjacent layers are stably packed together and
      exhibit interesting 3-D supramolecular arrays pi-pi interactions of the 2,2'-bipy
      groups.

PMID- 14731045
TI  - Synthesis of linear and cyclic carbophosphazenes via an oxidative chlorination
      strategy.
AB  - The use of a mild, oxidative chlorination route for the synthesis of linear and
      cyclic carbophosphazenes is described. For example, chlorination of the linear
      PNCN chain Ph(2)P-N=C(Ph)-N(SiMe(3))(2) (1) with C(2)Cl(6) led to the clean
      formation of the previously known 8- and 6-membered rings [Ph(2)PNC(Ph)N](2) (2)
      and [Ph(2)PNC(Ph)NP(Ph)(2)N] (3), respectively. In a similar fashion, the N-alkyl
      substituted PNCN derivatives, Ph(2)P-N=C(Ph)-N((t)Bu)SiMe(3) (4) and Ph(2)P
      N=C(Ph)-N(i)Pr(2) (7) were readily converted by C(2)Cl(6) into the halogenated
      derivatives ClPh(2)P=N-C(Ph)=N(t)Bu (5) and [ClPh(2)P=N=C(Ph)-N(i)Pr(2)]Cl (8),
      respectively. Protonation of 5 was accomplished using HCl and gave the
      carbophosphazenium salt [ClPh(2)P=N-C(Ph)=N((t)Bu)H]Cl (6). In addition, the
      isolation of a rare 8-membered P(2)N(4)C(2) heterocycle
      [(Cl(3)P=N)ClPNC(Ph)NP(Cl)(2)NC(Ph)N] (9) from the reaction of PCl(5) and
      Li[PhC(NSiMe(3))(2)] is reported. Treatment of 9 with one equivalent of GaCl(3)
      led to the discovery of an unusual Lewis acid-induced ring contraction reaction
      whereby the (PNCN)(2) ring in 9 is converted into the novel 6-membered P(2)N(3)C
      heterocyclic adduct [(Cl(3)P=N)ClPNP(Cl)(2)NC(Ph)N].GaCl(3) (10) with concomitant
      release of PhCN. Structural characterization of compounds 1, 5, 6, and 8-10 by
      single-crystal X-ray diffraction is also provided.

PMID- 14731046
TI  - Syntheses, luminescence behavior, and assembly reaction of
      tetraalkynylplatinate(II) complexes: crystal structures of
      [Pt((t)Bu(3)trpy)(Ctbd1;CC(5)H(4)N)Pt((t)Bu(3)trpy)](PF(6))(3) and
      [Pt(2)Ag(4)(Ctbd1;CCtbd1;CC(6)H(4)CH(3)-4)(8)(THF)(4)].
AB  - A series of tetraalkynylplatinate(II) complexes, (NBu(4))(2)[Pt(Ctbd1;CR)(4)] (R
      = C(6)H(4)N-4, C(6)H(4)N-3, and C(6)H(3)N(2)-5), and the diynyl analogues,
      (NBu(4))(2)[Pt(Ctbd1;CCtbd1;CR)(4)] (R = C(6)H(5) and C(6)H(4)CH(3)-4), have been
      synthesized. These complexes displayed intense photoluminescence, which was
      assigned as metal-to-ligand charge transfer (MLCT) transitions. Reaction of
      (Bu(4)N)(2)[Pt(Ctbd1;CC(5)H(4)N-4)(4)] with 4 equiv of
      [Pt((t)Bu(3)trpy)(MeCN)](OTf)(2) in methanol did not yield the expected
      pentanuclear platinum product,
      [Pt(Ctbd1;CC(5)H(4)N)(4)[Pt((t)Bu(3)trpy)](4)](OTf)(6), but instead afforded a
      strongly luminescent 4-ethynylpyridine-bridged dinuclear complex,
      [Pt((t)Bu(3)trpy)(Ctbd1;CC(5)H(4)N)Pt((t)Bu(3)trpy)](PF(6))(3,) which has been
      structurally characterized. The emission origin is assigned as derived from
      states of predominantly (3)MLCT [d(pi)(Pt) --> pi((t)Bu(3)trpy)] character,
      probably mixed with some intraligand (3)IL [pi --> pi(Ctbd1;C)], and ligand-to
      ligand charge transfer (3)LLCT [pi(Ctbd1;C) --> pi((t)()Bu(3)trpy)] character. On
      the other hand, reaction of (Bu(4)N)(2)[Pt(Ctbd1;CCtbd1;CC(6)H(4)CH(3)-4)(4)]
      with [Ag(MeCN)(4)][BF(4)] gave a mixed-metal aggregate,
      [Pt(2)Ag(4)(Ctbd1;CCtbd1;CC(6)H(4)CH(3)-4)(8)(THF)(4)]. The crystal structure of
      [Pt(2)Ag(4)(Ctbd1;CCtbd1;CC(6)H(4)CH(3)-4)(8)(THF)(4)] has also been determined.
      A comparison study of the spectroscopic properties of the hexanuclear platinum
      silver complex with its precursor complex has been made and their spectroscopic
      origins were suggested.

PMID- 14731047
TI  - Synergic nitrogen source route to inorganic fullerene-like boron nitride with
      vessel, hollow sphere, onion, and peanut nanostructures.
AB  - In this paper we describe the large-scale synthesis of inorganic fullerene-like
      (IF-like) hexagonal boron nitride with vessel, hollow sphere, peanut, and onion
      structures by reacting BBr(3) with the synergic nitrogen sources NaNH(2) and
      NH(4)Cl at 400-450 degrees C for 6-12 h. The composition of products could be
      confirmed to be pure boron nitride with hexagonal structures by the XRD patterns
      and FT-IR, XPS, and EDXA spectra. The representative HRTEM images clearly reveal
      the layerlike features of the products. Here, the peanut-like structure of the IF
      like BN is reported for the first time, and added to the list as one kind of new
      morphology of BN nanomaterials. The similarity in the structure between h-BN and
      graphite is responsible for the formation of IF-like BN with nanostructures of
      vessels, hollow spheres, peanuts, and onions.

PMID- 14731048
TI  - Syntheses, structures, photoluminescence, and theoretical studies of d(10) metal
      complexes of 2,2'-dihydroxy-[1,1']binaphthalenyl-3,3'-dicarboxylate.
AB  - The free solvated ligand, H(2)bna.CH(3)OH.H(2)O (1), and its dimeric complex,
      [Cd(2)(bna)(2)(H(2)O)(6)] (2) (bna = 2,2'-dihydroxy-[1,1']-binaphthalene-3,3'
      dicarboxylate), were obtained by evaporation of the solutions, while two new
      d(10) metal-hydroxy cluster-based coordination polymers, namely
      [Cd(8)(OH)(4)(H(2)O)(10)(bna)(6)].17H(2)O (3) and
      [Hpy](2)[Zn(4)(OH)(2)(H(2)O)(2)(bna)(4)].2H(2)O.2CH(3)CN (4), were obtained by a
      hydrothermal route. All the compounds have been characterized by X-ray
      crystallography and photoluminescence measurements. Compound 1 consists of a
      three-dimensional, hydrogen-bonded supramolecular array, 2 exhibits a dimeric
      molecule featuring a square motif organized by two Cd(II) atoms and two bna
      ligands each at the corner, and 3 contains unprecedented [Cd(8)(micro(3)
      OH)(2)(micro-OH)(2)(micro-H(2)O)(2)](12+) octanuclear metallacrown cores which
      are interlinked through bna to afford a two-dimensional structure, while 4
      features layers with butterfly-shaped [Zn(4)(micro(3)-OH)(2)](6+) clusters. All
      the complexes display photoluminescent properties in the blue/green range. The
      manifestation of photoluminescence, as probed by molecular orbital calculations
      performed on the complexes and also on hypothetical multinuclear complexes, is
      attributed to a ligand-to-metal charge-transfer mechanism. In addition to
      presenting a new approach for the study of the photoluminescent properties of
      metal-cluster-based coordination polymers by using simple model compounds, the
      study also reveals the dominant role of the structure of the ligand over that of
      the d(10) metal-hydroxy (or oxy) cluster and the presence of the cluster
      significantly increasing the emission lifetime.

PMID- 14731049
TI  - The generation gap: differences between children and adults pertinent to economic
      evaluations of health interventions.
AB  - Differences between children and adults have both technical and ethical
      implications for the design, interpretation and employment of economic analyses
      of health-related programmes. Even though policy makers increasingly turn to
      economic analyses to inform decisions about resource allocation, pertinent child
      adult differences have received fragmented discussion in leading methodological
      references. Key areas warranting attention include: the ways in which a child's
      distinctive biology modifies the cost and effectiveness of healthcare
      interventions; challenges in assessing utilities for infants and young children
      given their limited but developing cognitive capacity; how a child's age,
      dependency and disability affect the selection of the appropriate time horizon
      and scope of the analysis; whether a child's non-wage earning productivity should
      be incorporated into analyses, and if so, what metric to use; what principles of
      equity policy makers should employ in using economic evaluations to choose
      between child- and adult-focused interventions; and whether special protective
      measures should be introduced to secure the rights and interests of children who
      cannot advocate for themselves.

PMID- 14731050
TI  - Health economic evaluation of non-melanoma skin cancer and actinic keratosis.
AB  - Non-melanoma skin cancer (NMSC) and actinic keratosis are becoming an
      increasingly important healthcare problem. There are approximately 1 million
      cases of NMSC in the US each year, primarily basal cell carcinomas, and the
      incidence is increasing. Although NMSC is significant in terms of both health
      risk and the resource implications for treatment within healthcare systems, our
      understanding of the health economics of NMSC is limited. The purpose of this
      article was to systematically review and assess published health economic studies
      of the treatment of NMSC and actinic keratosis, taking into consideration key
      aspects of guidelines set by drug purchasers and key reimbursement agencies, and
      to provide recommendations for appropriate modelling approaches and data
      collection for health economic studies of NMSC and actinic keratosis. We
      systematically reviewed the published literature from 1965 to 2003 for health
      economic evaluations of treatments of NMSC and actinic keratosis using the search
      terms: ('skin cancer' or 'non melanoma skin cancer' or 'basal cell carcinoma' or
      'actinic keratosis') and ('decision model' or 'decision theoretic' or 'decision
      analytic' or 'health economic' or 'cost effective'). Studies using one of the
      following methodologies were included: cost-effectiveness, cost-benefit, cost
      utility, cost-minimisation, cost-of-illness, cost-consequence, and treatment cost
      analysis. We identified eight studies evaluating NMSC. One of these studies also
      evaluated actinic keratosis. Although several studies satisfied some of the basic
      requirements of health economic evaluations, the majority had serious
      shortcomings that limit their usefulness. There are a few high-quality health
      economic evaluations assessing treatments for NMSC or actinic keratosis. However,
      our analysis suggests that additional data on treatment practice patterns and
      epidemiology need to be collected, and incorporated with efficacy and safety data
      in a formal decision-analytic framework to assist decision makers in allocating
      scarce healthcare resources.

PMID- 14731051
TI  - Cost of stress urinary incontinence: a claims data analysis.
AB  - OBJECTIVES: The primary objectives of this research were to: (i) identify and
      present methodologies for estimating three types of 'cost-of-illness' measures
      using healthcare and disability claims data -- specifically 'cost of treatment',
      'incremental cost of patient', and 'incremental cost of illness'; and (ii)
      perform a case-study analysis of these cost measures for women treated for stress
      urinary incontinence (SUI). STUDY DESIGN AND METHODS: In this paper, we discuss
      aspects of cost-of-illness methodologies in the context of SUI. We first
      distinguish between 'cost of treatment' (i.e. the costs of treating a specific
      condition), 'incremental cost of patient' (i.e. the additional costs associated
      with patients with a particular condition, irrespective of any comorbid
      conditions they may also have), and 'incremental cost of illness' (i.e. the
      additional costs resulting from a particular illness, as distinct from the costs
      of other conditions that the patient might have, including conditions which might
      have caused the illness in question). The latter case is in many ways the most
      complex to model, requiring controls for related causal conditions. We then
      applied these three methodologies by analysing the costs associated with SUI.
      Using data from a large employer claims database (n > 100 000), we estimated a
      series of regression models that reflected cost of treatment, incremental cost of
      patient, and incremental cost of illness for SUI. RESULTS: The three approaches
      yielded substantially different results. For many purposes the incremental cost
      of-illness model provides the most appropriate results, as it controls for
      comorbid conditions, as well as patient demographics. On a per capita basis using
      the incremental cost-of-illness model, patients with SUI had direct costs that
      were 134% more than those for their controls and indirect costs that were 163%
      more than those for controls. Estimating costs for the average (i.e. mean) person
      results in dollar-termed estimates of the costs of SUI. In particular, we found
      that in 1998, the average direct medical cost of SUI was $US5642 and the indirect
      workplace cost of SUI was $US4208. CONCLUSIONS: Since the various methods yield
      substantially different results, it is important that the end user of cost-of
      illness analyses of claims data have a clear purpose in mind when reporting the
      cost of the condition of concern. The incremental cost-of-illness measure for
      claims data has substantial advantages in terms of enhancing our understanding of
      the specific cost impact of SUI.

PMID- 14731053
TI  - Economic evaluation of varicella vaccination programmes: a review of the
      literature.

PMID- 14731052
TI  - Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis.
AB  - Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD),
      binds to and inhibits the activity of tumour necrosis factor-alpha, which is
      thought to play an important role in the pathophysiology of rheumatoid arthritis.
      Intravenous infliximab plus methotrexate is recommended in patients with
      rheumatoid arthritis who have not achieved satisfactory disease control with
      adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on
      efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor
      Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in
      patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks
      plus methotrexate demonstrated rapid and sustainable improvements in clinical
      response, delayed radiographic progression, and/or improved functional status and
      health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and
      102. In cost-utility analyses of infliximab plus methotrexate conducted from a
      healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden
      and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated
      with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios
      relative to methotrexate alone in patients with active, refractory rheumatoid
      arthritis. When only direct costs were considered, the lifetime incremental cost
      per discounted QALY gained with infliximab plus methotrexate relative to
      methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported;
      treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses,
      and euro39 500 (year of costing not reported; lifelong treatment) in the
      Portuguese analysis. The cost-utility ratios were more favourable when lost
      productivity costs or the additional benefit of infliximab on radiographic
      stabilisation were considered. In the Swedish and UK analyses with a 10-year time
      horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost
      utility ratios of euro28 600-56 100 (year of costing not reported) when direct
      costs were considered, and euro3440-48 200 when direct costs plus loss-of
      productivity costs were considered. In conclusion, cost-utility analyses, which
      were based on modelling of data from the pivotal clinical trial of infliximab
      plus methotrexate, indicate that infliximab plus methotrexate is associated with
      acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained)
      relative to methotrexate monotherapy in patients with active rheumatoid arthritis
      who have not responded to previous methotrexate or other DMARD therapy. The cost
      effectiveness of infliximab versus other DMARDs is at present unclear, but will
      be clarified when appropriate data from directly comparative clinical and/or
      pharmacoeconomic studies become available. In patients in whom adequate courses
      of other DMARDs have failed to achieve satisfactory disease control, infliximab
      plus methotrexate may prevent or delay disability, which may produce reductions
      in nondrug costs that can help offset its acquisition cost.

PMID- 14731055
TI  - Neuropsychotherapeutics in the UK: what has been the impact of NICE on
      prescribing?
AB  - The UK National Institute for Clinical Excellence (NICE) was set up in 1999 to
      advise the National Health Service (NHS) on the use of new technologies largely,
      but not exclusively, on the basis of their clinical and cost effectiveness. There
      have been problems with this, as with any developing system, most of which have
      arisen from issues not directly under the control of NICE. Despite this, NICE has
      already achieved a pivotal role in determining the uptake of new therapies into
      the NHS. In the area of neuropsychiatric therapies, NICE has examined a number of
      topics and has generally facilitated the increased use of the agents examined,
      approving the use, within limitations, of such drugs as riluzole, atypical
      antipsychotics and cholinesterase inhibitors. Although the use of some of these
      therapies had been growing, it had previously been restricted by funding in the
      NHS. As a result of NICE guidance, these funding restrictions have generally been
      lifted. NICE has rejected one area of neurological therapy so far--that of
      interferon-beta products and glatiramer acetate for multiple sclerosis--on the
      grounds of clinical uncertainty about long-term benefits and poor cost
      effectiveness. However, the UK Government has created a novel risk-sharing scheme
      in collaboration with the sponsoring companies to make these drugs available at a
      level of cost effectiveness acceptable to the NHS. The feasibility of this scheme
      is as yet unclear. This might be seen as either a triumph for NICE or as an
      undermining of it for political ends. One interesting aspect that is more
      prominent in neuropsychiatric disorders than in other areas of NICE activity has
      been the power of patient advocacy in encouraging acceptance of therapies where
      the evidence base was weak or the incremental cost-effectiveness ratio was
      unfavourable. The principles behind the activities of NICE attract wide support
      within the NHS, but the details of its decisions have often not been popular
      within NHS management who have to deliver them. Some of this relates more to the
      context and political environment within which NICE operates than to a failing
      within NICE itself. NICE will continue to become increasingly important in
      determining the use of new drugs within the UK NHS.

PMID- 14731056
TI  - Opioid therapy in patients with a history of substance abuse.
AB  - A range of aberrant drug-taking behaviours can occur in patients who are
      undergoing treatment for chronic pain, especially if opioid therapy is involved.
      Assessing and understanding these behaviours, and their relationship to addiction
      (or substance use disorder), can be difficult but it is necessary for assuring
      quality pain management. Aberrant drug-taking behaviour may be evident, for
      example, when a patient with pain is unilaterally escalating doses of opioids or
      using the medications to treat other symptoms or when prescriptions are being
      mishandled. In patients with a history of substance abuse, these are often
      serious developments to which a clinician must know how to react. These complex
      behaviours may be indicative of addiction or may be simply a reaction to under
      medicated pain. The clinician therefore is challenged to understand such
      behaviours and plan interventions accordingly. Although it is becoming
      increasingly common to avoid opioid therapy in patients demonstrating such
      challenging behaviours for fear of regulatory scrutiny, clinical management can
      be tailored to address the many possibilities that might be giving rise to such
      behaviours. In addition, control over prescriptions can be accomplished without
      necessarily terminating the prescribing of controlled substances entirely.
      Optimal medical management of chronic pain in those patients with addiction
      problems or engaging in problematic behaviours involves careful, ongoing
      assessment by the clinician as well as a tailored management approach. This
      approach should use multiple structures including strict contracts, prudent drug
      selection and frequent follow-ups to pain and addiction treatments, including the
      use of urine toxicology screening, to maximise the likelihood of a good outcome.

PMID- 14731057
TI  - Role of dopamine receptor agonists in the treatment of restless legs syndrome.
AB  - The restless legs syndrome (RLS) is defined by four essential criteria obligatory
      for clinical diagnosis which were established, and recently revised, by the
      International RLS Study Group. These are (i) the urge to move the legs, usually
      accompanied or caused by uncomfortable and unpleasant sensations in the legs,
      which are (ii) worse during rest/inactivity, (iii) partially or totally relieved
      by movement and (iv) worse at night/in the evening. Treatment with levodopa leads
      to symptom relief, but augmentation (occurrence of symptoms before levodopa
      administration in the evening) may occur, limiting the long-term use of this
      drug. This article gives an overview of the treatment in general and the role of
      dopamine receptor agonists in the therapy of RLS and periodic limb movements
      (PLMs). Dopamine receptor agonists are widely used as an effective treatment for
      RLS and PLMs, presumably because of their longer half-lives, lower likelihood of
      augmentation and good tolerability compared with levodopa. It was shown that, for
      example, pergolide, ropinirole, pramipexole and cabergoline alleviated RLS
      symptoms in 70-90% of patients. A new non-oral (transdermal) formulation of one
      dopamine receptor agonist, rotigotine, has recently been developed and shown to
      be efficacious in RLS. Further research should focus on long-term observations
      and comparisons of different dopamine receptor agonists in RLS.

PMID- 14731058
TI  - Cognitive effects of long-term benzodiazepine use: a meta-analysis.
AB  - INTRODUCTION: While benzodiazepines are the most widely used psychotropic drugs,
      there are relatively few studies that have examined deficits in cognitive
      functioning after long-term use. The literature that is available is difficult to
      interpret due to conflicting results as well as a variety of methodological
      flaws. OBJECTIVE: To systematically evaluate and integrate the available research
      findings to determine the effect of long-term benzodiazepine use on cognitive
      functioning using meta-analytical techniques. METHODS: Thirteen research studies
      that employed neuropsychological tests to evaluate cognitive performance after
      long-term use of benzodiazepine medication met inclusion criteria. The
      neuropsychological tests employed in these 13 studies were each categorised as
      measuring one of 12 cognitive domains. Separate effect sizes were calculated for
      each of the 12 cognitive categories. Each study was only allowed to contribute
      one effect size to each cognitive category by averaging together the effect sizes
      from the same study if more than one type of test was used to measure a
      particular category. This strategy resulted in equal weight being given to each
      study per category, regardless of the number of tests in that category. RESULTS:
      The overall mean number of patients who were benzodiazepine users was 33.5 (SD +/
      28.9) and the mean number of controls was 27.9 (SD +/- 19.6). The duration of
      benzodiazepine use ranged from 1 to 34 (mean 9.9) years. Long-term benzodiazepine
      users were consistently more impaired than controls across all cognitive
      categories examined, with effect sizes ranging in magnitude from -1.30 to -0.42.
      The mean weighted effect size was -0.74 (SD +/- 0.25). None of the effect sizes
      had 95% CIs that spanned zero and, therefore, all of these effects were
      significant and different to zero. CONCLUSION: Moderate-to-large weighted effect
      sizes were found for all cognitive domains suggesting that long-term
      benzodiazepine users were significantly impaired, compared with controls, in all
      of the areas that were assessed. However, this study has several limitations, one
      being that it includes a relatively small number of studies. Further studies need
      to be conducted; ideally, well designed, controlled studies that thoroughly
      investigate certain areas of cognitive functioning and present data in such a way
      so as to be amenable to inclusion in a meta-analysis. Incorporating the
      information from these studies into a larger meta-analysis would allow for a more
      thorough and statistically sound investigation of the effects of moderator
      variables. The observation that long-term benzodiazepine use leads to a
      generalised effect on cognition has numerous implications for the informed and
      responsible prescription of these drugs.

PMID- 14731059
TI  - Zotepine for behavioural and psychological symptoms in dementia: an open-label
      study.
AB  - OBJECTIVE: To provide initial information on the safety and efficacy of the
      atypical antipsychotic zotepine in the treatment of behavioural and psychological
      symptoms of dementia (BPSD). METHODS: This was an open-label, single-centre field
      study. Twenty-four patients with BPSD associated with Alzheimer's disease (n=12)
      or other forms of dementia (n=12) were included. During the 8-week observation
      period, the patients received zotepine (Nipolept) [12.5-150 mg/day] for the
      psychotic components of BPSD; no other treatment interventions for BPSD were
      allowed. At baseline, day 28 and day 56, patients were evaluated using the
      Clinical Global Impressions (CGI) scale; the Mini-Mental State Examination
      (MMSE), the Syndrome Brief Test (SKT) and the Age Concentration Test (AKT) to
      assess cognition; and the Neuropsychiatric Inventory (NPI) and the Cohen
      Mansfield Agitation Inventory (CMAI) to assess BPSD. General adverse effects and,
      more specifically, the emergence of extrapyramidal symptoms were also assessed.
      RESULTS: There was no change from baseline to day 56 in the CGI score and the
      caregiver burden (as indicated by the caregiver-related section of the NPI).
      There was also no change in cognition (as assessed by the MMSE, SKT and AKT). The
      neuropsychiatric symptom score according to part 1 of the NPI (especially key
      psychotic symptoms, aggression and disinhibition) and the CMAI scores improved by
      36% and 15%, respectively, between baseline and the end of the study in a highly
      statistically significant fashion. No significant differences in treatment
      response or adverse effect profile were noted between the 12 patients with
      Alzheimer's disease and the 12 patients with other types of dementia. Zotepine
      was well tolerated, with tiredness and sedation (five and four cases,
      respectively) being the most frequent complaints. No clinically significant
      emergence of extrapyramidal symptoms was seen. CONCLUSIONS: Zotepine appears to
      be well tolerated and effective in treating BPSD, consistent with the performance
      of other atypical antipsychotic drugs in this condition. Larger, controlled
      studies are warranted.

PMID- 14731060
TI  - Spotlight on oxcarbazepine in epilepsy.
AB  - Oxcarbazepine (Trileptal, Timox) is structurally related to carbamazepine and has
      anticonvulsant activity. Studies suggest that the anticonvulsant activity of
      oxcarbazepine is mediated via the blocking of neuronal ion channels. In patients
      aged <18 years, the efficacy of oxcarbazepine monotherapy was similar to that of
      phenytoin in children with partial onset or generalised tonic-clonic seizures in
      a 48-week trial. Additional supporting findings demonstrated that 43-71% of
      patients with partial onset, generalised or undetermined epilepsy were seizure
      free after oxcarbazepine monotherapy (mean dosage 27.7-50 mg/kg/day; duration 1-5
      years). In contrast, one small nonblind trial showed more patients treated with
      oxcarbazepine monotherapy than with carbamazepine monotherapy had recurrent
      seizures during 16 months of therapy (although the conclusions that can be drawn
      from this trial are limited). As adjunctive therapy, oxcarbazepine was
      significantly better than placebo at reducing seizure frequency in children and
      adolescents with refractory partial onset seizures with or without secondary
      generalisation: the median percentage change in partial onset seizure frequency
      was 35% versus 9%, respectively, during 16 weeks of therapy. In noncomparative
      trials of adjunctive oxcarbazepine (mean dosage of 34.5-56.7 mg/kg/day), 7-11% of
      patients with partial onset or generalised seizures were seizure free during
      treatment, and 20-54% had seizure reductions of > or =50%. Oxcarbazepine was
      generally well tolerated during monotherapy and adjunctive therapy; 2.5% and 10%
      of patients withdrew from well controlled trials of oxcarbazepine monotherapy and
      adjunctive therapy. Oxcarbazepine monotherapy was better tolerated than phenytoin
      and events observed in oxcarbazepine-treated patients were transient.
      Oxcarbazepine metabolism is largely unaffected by induction of the cytochrome
      (CYP) P450 system. However, oxcarbazepine can inhibit CYP2C19 and induce CYP3A4
      and CYP3A5, thereby interfering with the metabolism of other drugs (e.g.
      phenytoin). In addition, oxcarbazepine decreases plasma levels of oral
      contraceptives and alternative contraceptive methods should be used. In
      conclusion, oxcarbazepine (as both monotherapy and adjunctive therapy) has shown
      efficacy in the treatment of partial onset seizures in children with epilepsy.
      Nevertheless, the generally favorable tolerability profile and relatively low
      potential for drug interactions of oxcarbazepine make it a valuable option in the
      treatment of childhood epilepsy.

PMID- 14731062
TI  - Leadership myths.

PMID- 14731061
TI  - Spotlight on lamotrigine in bipolar disorder.
AB  - Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established
      anticonvulsant agent that has shown efficacy in the prevention of mood episodes
      in adult patients with bipolar I disorder. The mechanism of action of the drug in
      patients with bipolar disorder may be related to the inhibition of sodium and
      calcium channels in presynaptic neurons and subsequent stabilisation of the
      neuronal membrane. Lamotrigine monotherapy significantly delayed time to
      intervention with additional pharmacotherapy or electroconvulsive therapy for any
      new mood episode (mania, hypomania, depression and mixed episodes), compared with
      placebo, in two large, randomised, double-blind trials of 18 months' duration.
      Additionally, lamotrigine was significantly superior to placebo at prolonging
      time to intervention for depression. These effects of lamotrigine were
      demonstrated in both recently manic/hypomanic and recently depressed patients.
      Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data
      only, although lithium was superior to lamotrigine on this measure. Two of four
      double-blind, short-term studies have shown lamotrigine to be more effective than
      placebo in the treatment of patients with treatment-refractory bipolar disorder
      or those with bipolar depression. Lamotrigine has not demonstrated efficacy in
      the treatment of acute mania. Lamotrigine was generally well tolerated in
      maintenance studies with the most common adverse events being headache, nausea,
      infection and insomnia. Incidences of diarrhoea and tremor were significantly
      lower in lamotrigine- than in lithium-treated patients. The incidence of serious
      rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and
      included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to
      cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period
      to 200 mg/day to minimise the incidence of serious rash. Adjustments to the
      initial and target dosages are required if coadministered with valproate
      semisodium or carbamazepine. CONCLUSION: Lamotrigine has been shown to be an
      effective maintenance therapy for patients with bipolar I disorder, significantly
      delaying time to intervention for any mood episode. Additionally, lamotrigine
      significantly delayed time to intervention for a depressive episode and showed
      limited efficacy in delaying time to intervention for a manic/hypomanic episode,
      compared with placebo. Although not approved for the short-term treatment of mood
      episodes, lamotrigine has shown efficacy in the acute treatment of patients with
      bipolar depression but has not demonstrated efficacy in the treatment of acute
      mania. Lamotrigine is generally well tolerated, does not appear to cause
      bodyweight gain and, unlike lithium, generally does not require monitoring of
      serum levels.

PMID- 14731063
TI  - There is no free lunch.

PMID- 14731065
TI  - Allelotypic characteristics of thorotrast-induced intrahepatic
      cholangiocarcinoma: comparison to liver cancers not associated with thorotrast.
AB  - To elucidate the genetic alterations that are specific to Thorotrast-induced
      liver cancers and their possible roles in tumorigenesis, we analyzed loss of
      heterozygosity (LOH) at 37 loci. Our previous study of liver cancers that were
      not associated with Thorotrast found LOH at 9 of these loci to be characteristic
      of intrahepatic cholangiocarcinoma (ICC), at 19 to be characteristic of
      hepatocellular carcinoma (HCC), and at 9 to be common to both ICC and HCC. LOH
      analysis was also performed in tissues of cholangiolocellular carcinoma, which is
      thought to originate from a common stem cell progenitor of hepatocytes and bile
      duct epithelial cells. We found frequent LOH at D4S1538, D16S2624 and D17S1303 to
      be common to all the subtypes of liver cancers, independent of the specific
      carcinogenic agent. In contrast, LOH at D4S1652 generally was not observed in
      Thorotrast-induced ICC. LOH analysis revealed that Thorotrast-induced ICC shares
      some LOH features with both ICC and HCC that were not induced by Thorotrast;
      however, it is more similar to ICC than to HCC in terms of genetic changes. This
      study could narrow down the crucial chromosomal loci whose deletions are relevant
      to hepatobiliary carcinogenesis irrespective of the carcinogenic agent. The study
      of LOH at loci other the those crucial ones may help us understand how the
      phenotype of liver cancers is determined.

PMID- 14731066
TI  - Radiation treatment decreases bone cancer pain, osteolysis and tumor size.
AB  - Radiotherapy is the cornerstone of palliative treatment for primary bone cancer
      in animals and metastatic bone cancer in humans. However, the mechanism(s)
      responsible for pain relief after irradiation is unknown. To identify the
      mechanism through which radiation treatment decreases bone cancer pain, the
      effect of radiation on mice with painful bone cancer was studied. Analysis of the
      effects of a 20-Gy treatment on localized sites of painful bone cancers was
      performed through assessments of animal behavior, radiographs and histological
      analysis. The findings indicated that radiation treatment reduced bone pain and
      supported reduced cancer burden and reduced osteolysis as mechanisms through
      which radiation reduces bone cancer pain.

PMID- 14731067
TI  - Response of Chinese hamster v79 multicellular spheroids exposed to high-energy
      carbon ions.
AB  - Chinese hamster V79-379A spheroids 200 +/- 30 microm (+/- SD) in diameter were
      irradiated in agitated medium in different oxygen atmospheres with (1) 227
      MeV/nucleon (12)C(+6) ions (plateau region) to model tissue in the entrance
      channel during therapy, (2) carbon ions in the extended Bragg peak modeling
      tissue in the target volume, or (3) X rays as a reference modality. Cell survival
      curves were similar for modes (1) and (3), indicating the absence of a contact
      effect and the presence of a pronounced oxygen effect with oxygen enhancement
      ratios (OERs) of 2.8 and 2.9, respectively. In contrast, the oxygen effect was
      substantially smaller in mode (2) with an OER of 1.4. Under normal or restricted
      oxygen supply conditions (external pO(2) = 145 or 0 mmHg), the relative
      biological effectiveness (RBE) was 2.1 or 4.3, respectively, for Bragg-peak
      irradiation. This modality induced apoptosis and a dose-dependent accumulation of
      cells in G(2)/M phase even at pO(2) = 0 mmHg. The volume ratios of treated to
      untreated spheroids exhibited cyclic variations after heavy-particle treatment
      that were not directly attributable to cell cycle synchronization. In summary,
      the results suggest that carbon ions in the extended Bragg peak are more
      effective than conventional X rays, particularly under hypoxic conditions.

PMID- 14731068
TI  - Evaluation of recombination repair pathways in thermal radiosensitization.
AB  - Thermal radiosensitization has been shown to cause inhibition of repair of
      sublethal and potentially lethal damage and DNA DSBs. In this study we assessed
      thermal radiosensitization in mutants deficient in homologous recombinational
      (HR) repair and nonhomologous end joining repair (NHEJ). Using cells of the mouse
      wild-type embryo fibroblast cell line MEF and its Ku80(-/-) derivative that is
      deficient in NHEJ, we showed that thermal radiosensitization is the same in both
      cell lines. Further studies with cells of the wild-type CHO-AA8 cell line and its
      derivative IRS(ISF), which is deficient in HR, also showed comparable thermal
      radiosensitization in both cell lines. Further experiments using cells of chicken
      DT40 cell lines also showed comparable thermal radiosensitization between the
      wild-type HR mutant Rad54, the NHEJ mutant Ku70, and the double mutant Rad 54
      Ku70. These results indicate that the HR and NHEJ pathways may not be targets for
      thermal radiosensitization.

PMID- 14731070
TI  - Measurement of DNA damage and apoptosis in Molt-4 cells after in vitro exposure
      to radiofrequency radiation.
AB  - To determine whether exposure to radiofrequency (RF) radiation can induce DNA
      damage or apoptosis, Molt-4 T lymphoblastoid cells were exposed with RF fields at
      frequencies and modulations of the type used by wireless communication devices.
      Four types of frequency/modulation forms were studied: 847.74 MHz code-division
      multiple-access (CDMA), 835.62 MHz frequency-division multiple-access (FDMA),
      813.56 MHz iDEN(R) (iDEN), and 836.55 MHz time-division multiple-access (TDMA).
      Exponentially growing cells were exposed to RF radiation for periods up to 24 h
      using a radial transmission line (RTL) exposure system. The specific absorption
      rates used were 3.2 W/kg for CDMA and FDMA, 2.4 or 24 mW/kg for iDEN, and 2.6 or
      26 mW/kg for TDMA. The temperature in the RTLs was maintained at 37 degrees C +/-
      0.3 degrees C. DNA damage was measured using the single-cell gel electrophoresis
      assay. The annexin V affinity assay was used to detect apoptosis. No
      statistically significant difference in the level of DNA damage or apoptosis was
      observed between sham-treated cells and cells exposed to RF radiation for any
      frequency, modulation or exposure time. Our results show that exposure of Molt-4
      cells to CDMA, FDMA, iDEN or TDMA modulated RF radiation does not induce
      alterations in level of DNA damage or induce apoptosis.

PMID- 14731069
TI  - Measurements of alkali-labile DNA damage and protein-DNA crosslinks after 2450
      MHz microwave and low-dose gamma irradiation in vitro.
AB  - In vitro experiments were performed to determine whether 2450 MHz microwave
      radiation induces alkali-labile DNA damage and/or DNA-protein or DNA-DNA
      crosslinks in C3H 10T(1/2) cells. After a 2-h exposure to either 2450 MHz
      continuous-wave (CW) microwaves at an SAR of 1.9 W/kg or 1 mM cisplatinum (CDDP,
      a positive control for DNA crosslinks), C3H 10T(1/2) cells were irradiated with 4
      Gy of gamma rays ((137)Cs). Immediately after gamma irradiation, the single-cell
      gel electrophoresis assay was performed to detect DNA damage. For each exposure
      condition, one set of samples was treated with proteinase K (1 mg/ml) to remove
      any possible DNA-protein crosslinks. To measure DNA-protein crosslinks
      independent of DNA-DNA crosslinks, we quantified the proteins that were recovered
      with DNA after microwave exposure, using CDDP and gamma irradiation, positive
      controls for DNA-protein crosslinks. Ionizing radiation (4 Gy) induced
      significant DNA damage. However, no DNA damage could be detected after exposure
      to 2450 MHz CW microwaves alone. The crosslinking agent CDDP significantly
      reduced both the comet length and the normalized comet moment in C3H 10T(1/2)
      cells irradiated with 4 Gy gamma rays. In contrast, 2450 MHz microwaves did not
      impede the DNA migration induced by gamma rays. When control cells were treated
      with proteinase K, both parameters increased in the absence of any DNA damage.
      However, no additional effect of proteinase K was seen in samples exposed to 2450
      MHz microwaves or in samples treated with the combination of microwaves and
      radiation. On the other hand, proteinase K treatment was ineffective in restoring
      any migration of the DNA in cells pretreated with CDDP and irradiated with gamma
      rays. When DNA-protein crosslinks were specifically measured, we found no
      evidence for the induction of DNA-protein crosslinks or changes in amount of the
      protein associated with DNA by 2450 MHz CW microwave exposure. Thus 2-h exposures
      to 1.9 W/ kg of 2450 MHz CW microwaves did not induce measurable alkali-labile
      DNA damage or DNA-DNA or DNA-protein crosslinks.

PMID- 14731071
TI  - Loss of wild-type Trp53 protein in mouse fibroblasts leads to increased
      radioresistance with consequent decrease in repair of potentially lethal damage.
AB  - It has been reported that the loss of function of Trp53 protein is associated
      with a reduction in the expression of radiation-induced potentially lethal damage
      (PLD). These studies, however, were carried out using either transformed or
      transfected cell lines, and other factors may have existed that could interfere
      with PLD repair. In this study, we used isogenic fibroblasts derived from Trp53
      knockout mice to study radiation sensitivity, PLD repair, and repair of DNA
      double-strand breaks (DSBs). Experiments were carried out using wild-type
      (Trp53(+/+)), heterozygous (Trp53(+/-)) and homozygous mutant (Trp53(-/-)) cells.
      This is an ideal system because the only difference in the three cell strains is
      the status of the Trp53 protein. DSB repair was measured by pulsed-field-gel
      electrophoresis (PFGE), while radiosensitivity and PLD repair were studied using
      the clonogenic survival assay. Cells were irradiated in plateau phase and then
      trypsinized and plated either immediately or 24 h later to allow for PLD repair.
      The results of Western blot analyses showed that Trp53(-/-) cells expressed a
      putative mutant form of Trp53 that was unable to transcriptionally activate
      Cdkn1a (p21) protein in response to irradiation. The Trp53(-/-) cells were
      significantly more radioresistant than the Trp53(+/+) cells, and this was
      associated with a moderate reduction in PLD repair. DNA repair experiments showed
      no difference in DSB rejoining capability between the two cell lines. In
      conclusion, our results show that loss of wild-type Trp53 leads to increased
      radioresistance with consequent reduction in PLD repair but with no effect on DNA
      DSB repair.

PMID- 14731072
TI  - Retinoids and TIMP1 prevent radiation-induced apoptosis of capillary endothelial
      cells.
AB  - Radiation-induced changes in capillaries constitute a basic injury in the
      pathogenesis of chronic radiation damage to the heart, lung, liver, kidney and
      brain. It is important to identify new radioprotectors for capillary endothelial
      cells for use during radiotherapy to minimize normal tissue damage and possibly
      to increase the deliverable dose. Previously we demonstrated that exposure to
      ionizing radiation (10 Gy) results in death of bovine adrenal capillary
      endothelial cells in confluent monolayers by apoptosis. We also showed that
      retinoids inhibit the growth of endothelial cells, induce their differentiation,
      down-regulate matrix metalloproteinase (MMP) production, and up-regulate tissue
      inhibitors of matrix metalloproteinases (TIMPs). In the present studies, we
      demonstrated that radiation (10 Gy) induced an immediate increase in the amounts
      and activation of MMP1 and MMP2 in the cell fraction and medium of bovine
      capillary endothelial cells followed by an incidence of apoptosis. We also
      obtained data indicating that radiation-induced apoptosis can be inhibited by
      exposing bovine capillary endothelial cells to all-trans-retinol or all-trans
      retinoic acid for 6 days before irradiation, even when the vitamins were removed
      24 h before irradiation. Finally, we determined that inhibition of MMPs by TIMP
      was sufficient to block radiation-induced apoptosis, suggesting that the
      mechanism of protection by retinoids is through the alteration of levels of MMPs
      and TIMPs produced by the cells.

PMID- 14731073
TI  - Prolongation of life span associated with immunological modification by chronic
      low-dose-rate irradiation in MRL-lpr/lpr mice.
AB  - Chronic low-dose-rate gamma irradiation at 0.35 or 1.2 mGy/h prolonged the life
      span of MRL-lpr/lpr mice carrying a deletion in the apoptosis-regulating Fas gene
      that markedly shortens life due to severe autoimmune disease. Immunological
      modifications as indicated by a significant increase of CD8(+) T cells and a
      significant decrease of CD3(+) CD45R/B220(+) as well as CD45R/B220(+) CD40(+)
      cells were found in parallel with amelioration of total-body lymphadenopathy,
      splenomegaly, proteinuria, and kidney and brain syndromes.

PMID- 14731074
TI  - Increase in endogenous spleen colonies without recovery of blood cell counts in
      radioadaptive survival response in C57BL/6 mice.
AB  - The radioadaptive survival response induced by a conditioning exposure to 0.45 Gy
      and measured as an increase in 30-day survival after mid-lethal X irradiation was
      studied in C57BL/6N mice. The acquired radioresistance appeared on day 9 after
      the conditioning exposure, reached a maximum on days 12-14, and disappeared on
      day 21. The conditioning exposure 14 days prior to the challenge exposure
      increased the number of endogenous spleen colonies (CFU-S) on days 12-13 after
      the exposure to 5 Gy. On day 12 after irradiation, the conditioning exposure also
      increased the number of endogenous CFU-S to about five times that seen in animals
      exposed to 4.25-6.75 Gy without preirradiation. The effect of the interval
      between the preirradiation and the challenge irradiation on the increase in
      endogenous CFU-S was also examined. A significant increase in endogenous CFU-S
      was observed when the interval was 14 days, but not 9 days. This result
      corresponded to the increase in survival observed on day 14 after the challenge
      irradiation. Radiation-inducted resistance to radiation-induced lethality in mice
      appears to be closely related to the marked recovery of endogenous CFU-S in the
      surviving hematopoietic stem cells that acquired radioresistance by
      preirradiation. Preirradiation enhanced the recovery of the numbers of
      erythrocytes, leukocytes and thrombocytes very slightly in mice exposed to a
      sublethal dose of 5 Gy, a dose that does not cause bone marrow death. There
      appears to be no correlation between the marked increase in endogenous CFU-S and
      the slight increase or no increase in peripheral blood cells induced by the
      radioadaptive response. The possible contribution by some factor, such as Il4 or
      Il11, that has been reported to protect irradiated animals without stimulating
      hematopoiesis is discussed.

PMID- 14731075
TI  - Radiation-induced edema is dependent on cyclooxygenase 2 activity in mouse brain.
AB  - Cerebrovascular dysfunction, characterized by compromise of the blood-brain
      barrier and formation of cerebral edema, is common during the acute period after
      brain irradiation and may contribute to delayed pathology (e.g. vascular
      collapse, white matter necrosis) that leads to functional deficits. Another
      response of normal brain tissue to radiation is the induction of inflammatory
      markers, such as cytokine expression and glial activation. In particular,
      radiation-induced neuroinflammation is associated with an elevation in
      cyclooxygenase 2 (COX2), one of two isoforms of the obligate enzyme in prostanoid
      synthesis and the principal target of non-steroid anti-inflammatory drugs. Since
      prostanoids serve as autocrine and paracrine mediators in numerous physiological
      and pathological processes, including vasoregulation, we investigated COX2
      protein expression and COX2-mediated prostanoid production in radiation-induced
      cerebral edema in male C57/BL6 mice. We found that radiation induces COX2 protein
      that is accompanied by specific increases in prostaglandin E(2) and thromboxane
      A(2) within 4 and 24 h after brain irradiation. Furthermore, we showed that
      treatment with NS-398, a selective COX2 inhibitor, attenuated prostanoid
      induction and edema formation. These results suggest that radiation-induced
      changes in vascular permeability are dependent on COX2 activity, implicating this
      enzyme and its products as targets for potential therapeutic treatment/protection
      from the effects of radiation on normal brain tissue.

PMID- 14731076
TI  - Early radiation-induced endothelial cell loss and blood-spinal cord barrier
      breakdown in the rat spinal cord.
AB  - Using a rat spinal cord model, this study was designed to characterize radiation
      induced vascular endothelial cell loss and its relationship to early blood-brain
      barrier disruption in the central nervous system. Adult rats were given a single
      dose of 0, 2, 8, 19.5, 22, 30 or 50 Gy to the cervical spinal cord. At various
      times up to 2 weeks after irradiation, the spinal cord was processed for
      histological and immunohistochemical analysis. Radiation-induced apoptosis was
      assessed by morphology and TdT-mediated dUTP nick end labeling combined with
      immunohistochemical markers for endothelial and glial cells. Image analysis was
      performed to determine endothelial cell and microvessel density using
      immunohistochemistry with endothelial markers, namely endothelial barrier
      antigen, glucose transporter isoform 1, laminin and zonula occludens 1. Blood
      spinal cord barrier permeability was assessed using immunohistochemistry for
      albumin and (99m)Tc-diethylenetriamine pentaacetic acid as a vascular tracer.
      Endothelial cell proliferation was assessed using in vivo BrdU labeling. During
      the first 24 h after irradiation, apoptotic endothelial cells were observed in
      the rat spinal cord. The decrease in endothelial cell density at 24 h after
      irradiation was associated with an increase in albumin immunostaining around
      microvessels. The decrease in the number of endothelial cells persisted for 7
      days and recovery of endothelial density was apparent by day 14. A similar
      pattern of blood-spinal cord barrier disruption and recovery of permeability was
      observed over the 2 weeks, and an increase in BrdU-labeled endothelial cells was
      seen at day 3. These results are consistent with an association between
      endothelial cell death and acute blood-spinal cord barrier disruption in the rat
      spinal cord after irradiation.

PMID- 14731077
TI  - Modification of radiation injury by ramipril, inhibitor of angiotensin-converting
      enzyme, on optic neuropathy in the rat.
AB  - Inhibitors of angiotensin-converting enzyme (ACE) have been used to reduce
      radiation-induced normal tissue injury. The present study was carried out to
      determine whether ramipril, one of the inhibitors of ACE, would ameliorate
      radiation-induced brain damage, using a well-characterized optic neuropathy model
      in the rat, one of the most critical and radiosensitive structures in the brain.
      The brains of adult Fischer rats were irradiated stereotactically with 30 Gy
      using a single collimated beam. Six months after irradiation and 1.5 mg/kg day(
      1) ramipril (started 2 weeks after irradiation), rats were assessed for optic
      nerve damage functionally, using visual evoked potential, and histologically.
      Results show that ramipril conferred significant modification of radiation
      injury, since rats receiving radiation alone showed a threefold lengthening in
      the mean peak latency in the visual evoked potential, whereas 75% of rats
      receiving radiation followed by ramipril had evoked potentials that resembled
      those of normal untreated control rats. The histology of irradiated and ramipril
      treated optic nerves appeared nearly normal, while there was significant
      demyelination in both optic nerves of irradiated rats. The study represents the
      first demonstration of prophylaxis of radiation injury by a carboxyl-containing
      ACE inhibitor, providing a pharmacological strategy designed to reduce radiation
      induced normal tissue damage.

PMID- 14731078
TI  - Radiation, the ideal cytotoxic agent for studying the cell biology of tissues
      such as the small intestine.
AB  - Epithelial tissues are highly polarized, with the proliferative compartment
      subdivided into units of proliferation in many instances. My interests have been
      in trying to understand how many cellular constituents exist, what their function
      is, and what the intercommunicants are that ensure appropriate steady-state cell
      replacement rates. Radiation has proven to be a valuable tool to induce cell
      death, reproductive sterilization, and regenerative proliferation in these
      systems, the responses to which can provide information on the number of
      regenerative cells (a function associated with stem cells). Such studies have
      helped define the epidermal proliferative units and the structurally similar
      units on the dorsal surface of the tongue. The radiation responses considered in
      conjunction with a wide range of cell kinetic, lineage tracking and somatic
      mutation studies together with complex mathematical modeling provide insights
      into the functioning of the proliferative units (crypts) of the small intestine.
      Comparative studies have then been undertaken with the crypts in the large bowel.
      In the small intestine, in which cancer rarely develops, various protective
      mechanisms have evolved to ensure the genetic integrity of the stem cell
      compartment. Stem cells in the small intestinal crypts are intolerant of
      genotoxic damage (including that induced by very low doses of radiation); they do
      not undergo cell cycle arrest and repair but commit an altruistic TP53-dependent
      cell suicide (apoptosis). This process is compromised in the large bowel by BCL2
      expression. Recent studies have suggested a second genome protection mechanism
      operating in the stem cells of the small intestinal crypts that may also have a
      TP53 dependence. Such studies have allowed the cell lineages and genome
      protection mechanisms operating the small intestinal crypts to be defined.

PMID- 14731079
TI  - The administrative colloquium: developing management and leadership skills for
      faculty.
AB  - OBJECTIVE: Development of leadership competencies has become a priority for many
      academic health science centers. However, traditional faculty development has
      focused almost exclusively on improving teaching skills. The process and outcomes
      of developing leadership skills for academic health science center faculty has
      not been extensively studied. METHODS: The University of Nebraska Medical Center
      (UNMC) created a year-long course, called the Administrative Colloquium, as a
      means to enhance faculty leadership skills. Completion of the course required
      attendance at 8 half-day workshop sessions, each devoted to teaching a leadership
      competency (eg, leading with vision, managing change) and completing a project
      with a project report (oral or poster presentation). Course evaluation was
      multifaceted. Attendees were queried multiple times by a pre- and poststrategy
      and retrospective pre- and poststrategy concerning their perceptions about
      knowledge obtained during the course. Paired t testing was used to determine
      statistical differences between the mean pre- versus postvalues and the
      retrospective pre- versus postvalues. Project content was qualitatively analyzed
      for themes. RESULTS: All comparisons of pre- and postdata and retrospective pre-
      and postdata were statistically significant (P <.05). Three themes arose from the
      analysis of projects: change, management, and interpersonal communications.
      CONCLUSIONS: The pre- and postknowledge data and the retrospective pre- and
      postknowledge data demonstrate that learning was significant as well as
      sustained. Qualitative analysis of the project content demonstrates that the
      participants were applying the course content to solving real-world problems.
      These results give preliminary support to the conclusion that the Administrative
      Colloquium has had an impact on faculty leadership development at UNMC.

PMID- 14731080
TI  - Lessons learned from community site administrators involved in pediatric
      community rotations.
AB  - OBJECTIVE: Prominent pediatric organizations agree that young physicians need to
      be trained for the role of patient advocate in the community. However,
      information on the community site administrators' perspective on such training is
      limited. Therefore, the objective of this study was to explore community site
      administrators' perceptions of the advantages and disadvantages to pediatric
      resident training at their centers. Understanding these perspectives may lead to
      better partnerships and experiences for both the residents and the community
      sites. METHODS: Twenty-eight community site administrators participating in 2
      residency community rotations located in Ohio and Florida were surveyed with a
      semistructured questionnaire. A qualitative data analysis methodology was used to
      explore the entire set of responses. Research team members reviewed the
      responses, coded them for emerging themes, and generated three themes: 1)
      awareness, 2) knowledge exchange, and 3) organizational issues. RESULTS: Fifty
      seven percent of site administrators responded. These administrators consistently
      indicated that they valued the opportunity to increase residents' awareness of
      the services their sites provided to the community. The administrators and
      families served by the agencies appeared to benefit from the medical knowledge
      exchange, and this was a significant advantage from the community site
      administrators' perspective. Finally, community sites identified organizational
      issues of complex scheduling as an area for improvement. CONCLUSIONS: These
      findings demonstrate the value community sites place on active, early involvement
      of pediatric residents with community agencies. We have also identified key
      points to improve the experiences for both community sites and residents during a
      community pediatric rotation.

PMID- 14731081
TI  - Effect of a teaching skills program on faculty skills and confidence.
AB  - BACKGROUND: Although education is a central mission of medical schools,
      effectiveness of faculty as teachers is variable, with many faculty lacking
      formal training. Therefore, a series of sessions around teaching skills was
      developed. OBJECTIVE: To improve the skill, confidence, and comfort levels of
      faculty who teach general pediatrics. METHOD: A faculty development program
      consisting of nine 1-hour sessions on a variety of topics and a 3-hour workshop
      on Feedback and Evaluation was provided to all faculty members in a single
      academic division. The program was evaluated with a needs assessment and a
      quantitative postprogram self-assessment. A qualitative e-mail survey was
      performed 3 years after completion to assess durability. RESULTS: The 13 full
      time faculty members (10 women) in the Community and General Pediatrics Division
      attended a mean of 6.5 sessions each (range 4-10). All 13 participants completed
      the 22-item postprogram survey regarding comfort with and knowledge of teaching
      techniques. Statistically significant change was seen for all items. Comments
      from the open-response section reflected specific improvement in the area of
      feedback and the need for increased time to focus on teaching. Responses to the
      follow-up survey (46% response rate) were positive about the program in general
      and about the continued use of the skills that were learned in the program.
      CONCLUSIONS: Busy general pediatric faculty attended a majority of sessions in a
      faculty development program on teaching. Skill and comfort levels significantly
      improved in many of the areas covered, and the skills were still being used 3
      years later.

PMID- 14731082
TI  - Meeting the computer technology needs of community faculty: building new models
      for faculty development.
AB  - OBJECTIVE: We aimed to identify the evolving computer technology needs and
      interests of community faculty in order to design an effective faculty
      development program focused on computer skills: the Teaching and Learning Through
      Educational Technology (TeLeTET) program. METHODOLOGY: Repeated surveys were
      conducted between 1994 and 2002 to assess computer resources and needs in a pool
      of over 800 primary care physician-educators in community practice in East Texas.
      Based on the results, we developed and evaluated several models to teach
      community preceptors about computer technologies that are useful for education.
      RESULTS: Before 1998, only half of our community faculty identified a strong
      interest in developing their technology skills. As the revolution in
      telecommunications advanced, however, preceptors' needs and interests changed,
      and the use of this technology to support community-based teaching became
      feasible. In 1998 and 1999, resource surveys showed that many of our community
      teaching sites had computers and Internet access. By 2001, the desire for
      teletechnology skills development was strong in a nucleus of community faculty,
      although lack of infrastructure, time, and skills were identified barriers. The
      TeLeTET project developed several innovative models for technology workshops and
      conferences, supplemented by online resources, that were well attended and
      positively evaluated by 181 community faculty over a 3-year period. CONCLUSIONS:
      We have identified the evolving needs of community faculty through iterative
      needs assessments, developed a flexible faculty development curriculum, and used
      open-ended, formative evaluation techniques to keep the TeLeTET program
      responsive to a rapidly changing environment for community-based education in
      computer technology.

PMID- 14731083
TI  - Outcomes results from the evaluation of the APA/HRSA Faculty Scholars Program.
AB  - BACKGROUND: The goal of the Ambulatory Pediatric Association/Health Resources and
      Services Administration National Faculty Development Scholars Program was to
      improve primary care education in the pediatric setting. The program evaluation
      focused on four stake-holder objectives: 1) increase the educational skills of
      community and generalist faculty; 2) create pediatric leadership focused on
      changing the culture within the medical community to support primary care
      education; 3) develop an infrastructure that supports sustained faculty
      development efforts at the local, regional, and national level; and 4) include
      content areas consistent with Health Resources and Services Administration
      contract requirements. METHODS: A multimethod evaluation plan, focused on the 107
      completing scholars, was implemented utilizing six evaluation instruments.
      RESULTS: Key outcomes from both quantitative and qualitative outcome measures
      reveal that all evaluation objectives were achieved. Scholars presented 438 local
      workshops and 161 regional/national workshops focused on pediatric education with
      a combined attendance of 7939 participants. More than half of the scholars have
      now assumed a leadership position in education associated with program
      participation. Ninety-three percent of the scholars reported
      organizational/infrastructure changes associated with their program participation
      ranging from increased numbers of community teaching sites to specific resource
      allocations to support of faculty development. CONCLUSIONS: The outcomes of this
      evaluation reveal that the faculty development program achieved its objectives,
      with participants leading workshops, impacting faculty development
      infrastructure, advancing their own careers, and being strategically positioned
      in leadership roles with the skills to improve primary care education in the
      ambulatory setting.

PMID- 14731084
TI  - The HRSA-APA Faculty Development Scholars Program: executive leadership track.
AB  - BACKGROUND: The work environment and characteristics and behaviors of leaders are
      key components to successful programs. Pediatric primary care education has
      suffered from a lack of effective leaders. OBJECTIVE: The Executive Leadership
      Track of the Health Services Resources Administration-Ambulatory Pediatrics
      Association (HRSA-APA) National Faculty Development Scholars Program was designed
      to develop a cadre of teaching faculty with the knowledge, attitudes, and skills
      to lead primary care faculty development efforts in their home institutions,
      regions, and the nation. METHODS: Senior faculty from each APA region were
      selected to participate in a basic series of three 2-day leadership workshops.
      Three workshops addressed topics shown to be essential to development of
      productive work environments, 3 emphasized career development, and 3 addressed
      development of effective administrative skills. Participants were expected to
      give at least one workshop in their home institution or region every 6 months.
      Outcome measures included number of scholars successfully completing the program,
      number of workshops given by scholars, number of participants in scholars'
      workshops, indicators of professional growth, and indicators of changes in their
      work environment that support medical education and teaching. RESULTS: Thirty-two
      scholars conducted 90 workshops attended by 1082 participants. Scholars reported
      professional accomplishment, including assuming positions of leadership and
      promotion. Changes to the scholar's work environment included increased emphasis
      on educational scholarship in promotion and tenure considerations, mission-based
      budgeting, and closer collaboration between academic and community faculty.
      CONCLUSION: The program participants became effective leaders of and advocates
      for medical education.

PMID- 14731085
TI  - APA/HRSA National Faculty Development Scholars Program: community-based teaching
      track.
AB  - OBJECTIVES: Goals and objectives of the APA/HRSA National Faculty Development
      Scholars Program are described in a companion article in this supplement. Program
      objectives of the Community-Based Teaching Track were to 1) identify individuals
      with faculty development skills to serve as regional leaders, conducting local
      and regional workshops; 2) create a national network of leaders, thereby
      promoting sustainability; and 3) increase educational contributions of office
      based preceptors. Participant objectives were to 1) meet expectations of the
      program; 2) possess knowledge, skills, and attitudes needed to recruit and retain
      community-based preceptors; 3) possess knowledge and skills needed to conduct
      faculty development workshops for practitioners; and 4) form local and national
      collegial networks. METHODS: Academicians and practitioners were selected to form
      2 cohorts, starting in 1999 (N = 20) and 2000 (N = 22), respectively. Workshops
      were developed on the basis of projected needs and iterative needs assessments of
      the participants. Each participant was required to conduct workshops between
      meetings, first locally and then regionally or nationally. OUTCOMES: Forty-two
      participants conducted 307 workshops attended by 3815 individuals. Participants
      reported specific knowledge and skills gained from the program and increases in
      multiple areas of competence. Networks were formed, leading to collaborative
      regional and national presentations and formation of an APA Faculty Development
      Special Interest Group. Participants reported increased recruitment of training
      sites and preceptors, with enhanced relationships. CONCLUSION: Program and
      participant objectives of the Community-Based Teaching Track were met, including
      implementation of multiple new workshops, development of skills, and creation of
      a support network to enhance the sustainability of that success.

PMID- 14731086
TI  - Overview of the educational scholarship track.
AB  - The educational scholarship track represented 1 of 3 tracks of the Ambulatory
      Pediatric Association/Health Resources and Services Administration faculty
      development initiative. Two cohorts of participants (N = 38), selected via a peer
      review process, took part in a series of three 2-day workshops presented over an
      18-month period designed to assist experienced pediatric faculty in becoming more
      proficient educators. The program was developed through an iterative needs
      assessment process and consisted of 7 major areas of study and skill development:
      principles of adult learning; teaching skills; feedback and evaluation; the
      workshop as a teaching and faculty development tool; curriculum development,
      implementation, and evaluation; research in medical education; and scholarship
      and promotion. At program completion, 35 scholars rated themselves on their pre-
      and postprogram competencies, demonstrating improvement in most areas. Scholars
      were required to lead educational workshops and reported having led a total of
      118 local and 64 regional or national workshops as part of their program
      participation. There are objective indications that scholars in this track were
      successful in furthering their careers in medical education.

PMID- 14731087
TI  - The APA/HRSA Faculty Development Scholars Program: introduction to the
      supplement.
AB  - BACKGROUND: The purpose of this project was to improve pediatric primary care
      medical education by providing faculty development for full-time and community
      based faculty who teach general pediatrics to medical students and/or residents
      in ambulatory pediatric community-based settings. Funding for the program came
      through an interagency agreement with the Health Resources and Services
      Administration (HRSA) and the Agency for Healthcare Research and Quality (AHRQ).
      METHODS: A train-the-trainer model was used to train 112 scholars who could teach
      skills to general pediatric faculty across the nation. The three scholar groups
      focused on community-based ambulatory teaching; educational scholarship; and
      executive leadership. RESULTS: Scholars felt well prepared to deliver faculty
      development programs in their home institutions and regions. They presented 599
      workshops to 7989 participants during the course of the contract. More than 50%
      of scholars assumed positions of leadership, and most reported increased support
      for medical education in their local and regional environments. CONCLUSIONS: This
      national pediatric faculty development program pioneered in the development of a
      new training model and should guide training of new scholars and advanced and
      continuing training for those who complete a basic program.

PMID- 14731088
TI  - Pediatric medication errors: what do we know? What gaps remain?

PMID- 14731089
TI  - Information technology: its importance to child safety.

PMID- 14731090
TI  - Reducing errors and promoting safety in pediatric emergency care.

PMID- 14731091
TI  - Pediatric patient safety in the ambulatory setting.

PMID- 14731092
TI  - Promoting safety in child and adolescent health care: conference overview.

PMID- 14731093
TI  - Sexual-history taking in the pediatric emergency department.

PMID- 14731094
TI  - Using an immunization registry: effect on practice costs and time.
AB  - INTRODUCTION: Immunization registries can consolidate immunization records
      scattered among different providers, allowing immunization documentation for
      legal purposes, generation of needed-immunization lists, inventory management,
      and outreach for underimmunized children. They have been endorsed by the Centers
      for Disease Control and Prevention and health professionals as a means of
      sustaining high immunization rates. However, some providers perceive the cost of
      registry use as a barrier to participation. We sought to determine the effects of
      registry use on cost and time. METHODS: We used a pre-post design and a cost
      accounting approach to measure labor costs and time for immunization-related
      activities possibly affected by registry use before development of a regional
      registry in Colorado and after the registry was being fully used. Two rural
      family practices, 2 rural community health centers (CHCs), 3 urban pediatric
      practices, and 2 rural public health agencies participated in both periods.
      RESULTS: Cost per shot increased slightly in the postregistry period for private
      practices and CHCs ($0.56 per shot in 2001 dollars) and public health agencies
      ($0.38). Since costs can increase for several reasons, including salary increases
      above inflation, we analyzed time spent per shot and found that staff time
      decreased for private practices and CHCs but increased substantially for public
      health agencies. CONCLUSIONS: The study findings suggest to private practices
      that registry participation can provide a net benefit by making the vaccination
      process more efficient and, absent above-average salary increases, less costly.
      Public health agencies, however, would have to rely exclusively on the registry
      and eschew the use of paper vaccination records to realize efficiencies seen by
      other practice types.

PMID- 14731095
TI  - A pilot study to determine the feasibility of the low glycemic index diet as a
      treatment for overweight children in primary care practice.
AB  - BACKGROUND: The prevalence of overweight children is increasing. Experimental
      evidence and specialty clinic trials suggest that a low glycemic index (LGI) diet
      could be an effective primary care-based treatment for overweight children.
      OBJECTIVE: Conduct a pilot study to determine whether parents of overweight
      children can lower the glycemic index (GI) of their child's diet after receiving
      brief instructions and a handout from their pediatrician; and the diet's impact
      on body mass index (BMI). PATIENTS: Children 5-12 years with BMIs greater than
      the 95th percentile. INTERVENTION: Brief description of the LGI diet and a
      handout categorizing foods based on their GI and sample meals. DESIGN:
      Nonrandomized, 12-week pilot study. MEASURES: BMI, 24-hour recall, and food
      frequency questionnaire (FFQ) at entry; 3-day food records at 3, 6, and 9 weeks;
      BMI, FFQ, and questionnaire at 12 weeks. A GI score derived from standard GI
      tables. RESULTS: Of 34 children initially enrolled, 15 completed the study. Of
      these, 14 lowered their GI score (mean initial score = 26.6; mean score at 12
      weeks 15.6; P <.0001). Mean daily carbohydrate (CHO) intake decreased by 73 g
      over the study period (P <.02), and mean daily caloric intake decreased by 292
      kcal (P <.02). All 15 parents described the diet as easy to understand; 10
      reported that their child was generally able to follow the diet. BMI Z-score
      decreased in 12 of 15 children. CONCLUSION: This pilot study suggests that
      implementing the LGI diet is feasible in primary care for some patients. Further
      study is warranted with larger study and comparison groups.

PMID- 14731096
TI  - Pediatric residency training on domestic violence: a national survey.
AB  - OBJECTIVE: Between 3.3 and 10 million children witness domestic violence (DV)
      each year. These children are at risk for both emotional and behavioral problems.
      In 1998, the American Academy of Pediatrics issued guidelines for pediatricians
      to screen for DV and for residency programs to include DV education. Prior
      studies have assessed practicing pediatricians' DV screening habits. This study
      was designed to assess chief residents' attitudes and training regarding DV
      screening. METHODS: A 53-question survey regarding residents' attitudes and
      training surrounding DV was mailed to the chief residents of all 194 nonmilitary
      US pediatric residency programs. Descriptive and inferential analyses were
      performed. RESULTS: Sixty-eight percent of surveys were returned. Sixty-eight
      percent of respondents were female. Although 93% of chief residents felt that
      pediatricians should screen for DV, only 21% screen every patient. Only 24%
      agreed or strongly agreed that they felt experienced in handling DV cases.
      Although 60% of respondents say that they received 11 or more hours of residency
      training in how to handle child abuse, the majority (80%) received 4 hours or
      less of DV training. Seventy-one percent agreed or strongly agreed that
      pediatricians do not screen secondary to lack of training. CONCLUSIONS: Pediatric
      chief residents believe that DV is a significant pediatric health problem.
      However, screening practices are variable. Most chief residents feel that their
      training was not sufficient to make them comfortable screening for DV. Chief
      residents demonstrated openness to incorporating DV training into their programs,
      indicating a positive environment for DV curricula.

PMID- 14731097
TI  - An analysis of patient care questions asked by pediatricians at an academic
      medical center.
AB  - BACKGROUND: General pediatricians' information needs are not presently well
      characterized in the literature. OBJECTIVE: To characterize the patient care
      information needs of academic medical center pediatricians by collecting and
      classifying questions generated in clinical settings, allowing pediatric
      educators and authors to more effectively meet the needs of pediatricians.
      METHODS: A semistructured telephone survey of pediatric residents and faculty at
      a midwestern US academic medical center over two 6-month periods. The main
      outcome measures were number of questions asked, age ranges, pediatric
      subspecialties, and generic question types. RESULTS: A total of 607 pediatrician
      questions were collected. The infant age range generated the most questions
      (34.1%), and other age groups were almost equally distributed. The most common
      pediatric specialties were pharmacology (34.1%), infectious diseases (9.1%),
      neurology/neurosurgery (5.1%), allergy/pulmonary (4.6%), and neonatology (4.6%).
      The most common generic questions asked were "What is the dosage of drug X?"
      (18.0%), "What is the treatment for condition X?" (15.2%), and "What is condition
      X?" (13.5%). There were qualitative differences between resident and faculty
      groups. CONCLUSIONS: The information needs of academic medical center
      pediatricians can be assessed and potentially serve as a foundation for the
      development of common and digital educational information resources. Resident and
      faculty groups showed some qualitative differences. Pediatricians need drug
      dosing information; clear condition definitions, including manifestation and
      clinical course descriptions; and physical finding and laboratory testing
      information. Educators and authors should highlight information concerning
      pharmacology and infectious diseases when developing educational and information
      resources.

PMID- 14731098
TI  - Latent class analysis: an illustrative application for education in the
      assessment of resident otoscopic skills.
AB  - BACKGROUND: There is no gold standard readily available in several components of
      the routine physical exam: one example is the otoscopic exam, where the gold
      standard is confirmation by tympanocentesis. Resident education does not
      typically include routine assessment by the gold standard, making estimates of
      trainee performance extremely difficult. This is one reason why the otoscopic
      examination is difficult to teach. Available techniques can assess diagnostic
      exams when there is no gold standard-one of these is latent class analysis.
      METHODS: We use latent class analysis, a form of regression analysis, to compare
      the ability of pediatric residents to diagnose effusion with pediatric
      otolaryngologists and tympanometry. We briefly outline the technique of how to
      complete latent class analysis and provide an operational plan to use the method
      to assess resident performance. RESULTS: The sensitivity and specificity of
      pediatric resident otoscopic examination to diagnose the presence of effusion was
      72% and 84%, respectively. Pediatric otolaryngologist sensitivity and specificity
      was 91% and 82%; tympanometry had a sensitivity of 70% and specificity 76%. Our
      estimates of the performance of otolaryngologists and tympanometry to diagnose
      effusion were the same as previously reported when these diagnosticians have been
      compared with the gold standard of tympanocentesis. CONCLUSIONS: Latent class
      analysis can help estimate otoscopic examination performance of residents. This
      technique can be incorporated into assessment in medical education.

PMID- 14731099
TI  - Assessing resident performance: commentary on latent class analysis.

PMID- 14731100
TI  - Factors associated with resident satisfaction with their continuity experience.
AB  - OBJECTIVE: To identify factors associated with resident satisfaction concerning
      residents' continuity experience. DESIGN AND METHODS: Continuity directors
      distributed questionnaires to residents at their respective institutions.
      Resident satisfaction was defined as satisfied or very satisfied on a Likert
      scale. The independent variables included 60 characteristics of the continuity
      experience from 7 domains: 1) patient attributes, 2) continuity and longitudinal
      issues, 3) responsibility as primary care provider, 4) preceptor characteristics,
      5) educational opportunities, 6) exposure to practice management, and 7)
      interaction with other clinic and practice staff. A stepwise logistic regression
      model and the Generalized Estimating Equations approach were used. RESULTS:
      Thirty-six programs participated. Of 1155 residents (71%) who provided complete
      data, 67% (n = 775) stated satisfaction with their continuity experience. The
      following characteristics (adjusted odds ratio [OR] and 95% confidence interval
      [CI]) were found to be most significant: preceptor as good role model, OR = 7.28
      ( CI = 4.2, 12.5); appropriate amount of teaching, OR = 3.25 (CI = 2.1, 5.1);
      involvement during hospitalization, OR = 2.61 (CI = 1.3, 5.2); exposure to
      practice management, OR = 2.39 (CI = 1.5, 3.8); good balance of general pediatric
      patients, OR = 2.34 (CI = 1.5, 3.6); resident as patient advocate, OR = 1.74 (CI
      = 1.2, 2.4); and appropriate amount of nursing support, OR = 1.65 (CI = 1.1,
      2.6). Future career choice, type of continuity site, and level of training were
      not found to be statistically significant. CONCLUSIONS: Pediatric resident
      satisfaction was significantly associated with 7 variables, the most important of
      which were the ability of the preceptor to serve as a role model and teacher. The
      type of continuity site was not significant. Residency programs may use these
      data to develop interventions to enhance resident satisfaction, which may lead to
      enhanced work performance and patient satisfaction.

PMID- 14731101
TI  - A view from the residents: effective preceptor role modeling is in.

PMID- 14731103
TI  - Lumps, bumps, and things that go itch in your office!

PMID- 14731105
TI  - Combining health promotion classroom lessons with health fair activities.
AB  - This article focuses on the important role of the school nurse in promoting
      healthy lifestyle choices through networking, resource identification, and
      working with community partners. "Everyone Is Healthy at Northeast" was a health
      promotion program designed and presented in two ways: classroom lessons and a
      health fair. There were interactive health promotion classroom lessons on topics
      such as proper hand washing, the effects of tobacco, and keeping one's heart
      healthy. These lessons were enhanced by community partners in delivering the
      healthy lifestyle message through a variety of teaching methods: music,
      interactive games, and hands-on visuals. The health promotion education program
      culminated in a schoolwide health fair that showcased the healthy lifestyle
      choice information at various stations. "Everyone Is Healthy at Northeast" was a
      success and promoted healthy lifestyle choices through creativity, collaboration,
      and support from the entire school community.

PMID- 14731106
TI  - Increasing self-efficacy and knowledge through a seizure education program for
      special education teachers.
AB  - Since the passage of the 1975 Education for All Handicapped Children Act and the
      1986 PL99-457 amendment, many children aged birth to 3 years with special health
      care needs are enrolled in early intervention programs. Educators working in
      early intervention services often need to respond to and manage seizure activity
      and medical emergencies for special needs children. To do so, they need to have
      knowledge and confidence in their ability to intervene effectively. This
      intervention study was designed to address the knowledge and self-efficacy of 28
      special needs educators on seizure management. The intervention resulted in
      increased knowledge, skills, and self-efficacy related to seizure management and
      their ability to interact supportively with families.

PMID- 14731107
TI  - Prediction of postpartum social support and symptoms of depression in pregnant
      adolescents: a pilot study.
AB  - Many pregnant adolescents remain in school, creating unique challenges for
      professionals to meet their educational and health needs. In this descriptive
      pilot study of pregnant adolescents (n = 26), 68% demonstrated symptoms of
      depression as measured by the Center for Epidemiologic Studies Depression Scale
      (CES-D). In addition, there was an expectation by the pregnant adolescent that
      postpartum social support received, as measured by the Postpartum Support
      Questionnaire, would be different from what is important to her. As an important
      part of the team, school nurses are uniquely positioned to screen pregnant
      adolescents for depression and to assist them in learning how to negotiate for
      the social support that is important to them.

PMID- 14731108
TI  - Evaluation of an educational program for adolescents with asthma.
AB  - In addition to challenges of adolescence itself, teens with asthma face demands
      of asthma management and risks of asthma sequelae, including fatalities. Few
      asthma educational programs specifically address their needs. In response to
      school nurse concern, this pilot study evaluated an adolescent asthma education
      program, the Power Breathing trade mark Program, together with individual
      coaching sessions in terms of general asthma knowledge and health status.
      Thirteen high school students, predominantly female and African American,
      participated over a 6-month period. Evaluation tools included the Child Health
      Survey for Asthma, a focus group interview, and a program evaluation
      questionnaire. Participants reported that knowledge gained improved trigger
      avoidance, increased medication adherence, and decreased the frequency of asthma
      episodes. They described the individual coaching sessions as helpful in
      assimilating and applying information. The Power Breathing Program and coaching
      sessions show promise as an asthma educational program particularly tailored to
      adolescents. This article suggests further evaluation of the program and
      describes implications for school nurses.

PMID- 14731109
TI  - School nurses' knowledge and beliefs about the management of children with ADD.
AB  - The purpose of this study was to examine school nurses' knowledge and beliefs
      about the management of children with attention deficit disorder (ADD). Seven
      hundred eighty-six school nurses responded to mailed surveys regarding their
      attitudes and knowledge about the management of children with attention deficit
      disorder. Surveys were mailed to school nurses randomly selected from the
      membership of the National Association of School Nurses. School nurses' knowledge
      of school management of ADD and their attitudes about physicians' participation
      as part of a team effort in this care were explored. School nurses responded that
      physicians should increase their efforts to educate children and parents about
      ADD. Recommendations for school nurses in the management of children with ADD are
      offered.

PMID- 14731110
TI  - School-based condom availability programs.
AB  - The repercussions of sexual activity among teens continue to be a significant
      issue in the United States. Detrimental consequences to unprotected sexual
      activity among teens include unintended pregnancy and acquiring a sexually
      transmitted disease (STD) or human immunodeficiency virus (HIV). It is estimated
      that each year approximately 3 million teens acquire an STD and 860,000 become
      pregnant. A variety of programs have been implemented in school systems in an
      attempt to reduce the STDs, HIV, and pregnancy among teens. One program is the
      distribution of condoms in the school. There are many factors that the school
      nurse must consider in the development of a school-based condom disbursement
      program. This article addresses school-based condom availability programs as well
      as issues for the school nurse to consider when implementing such a program.

PMID- 14731111
TI  - Caring for children with cystic fibrosis: a collaborative clinical and school
      approach.
AB  - Earlier diagnosis and more effective treatments have improved both morbidity and
      mortality associated with cystic fibrosis, making regular school attendance a
      reality. School nurses have a unique opportunity to assist students with cystic
      fibrosis successfully manage their disease. Medical treatment for cystic fibrosis
      can be complex, leaving students and families in need of health consultation and
      support. The clinic and school nurse each brings a unique perspective to cystic
      fibrosis care management. Working to understanding perspectives across settings
      and looking for ways to collaborate through mutual planning and goal setting is
      an ideal way to support families and promote achievement of optimal health status
      for students.

PMID- 14731119
TI  - Legend of hepatitis B vaccination: the Taiwan experience.
AB  - Hepatitis B, a disease entity currently affecting more than 350 million persons
      worldwide, is also a serious health problem in Taiwan. Liver cirrhosis and
      hepatoma, which are both closely correlated with hepatitis B, are among the 10
      leading causes of death in Taiwan. A mass hepatitis B vaccination program,
      conducted by the government of Taiwan, was started in 1984. Prior to this
      vaccination program, a series of viral epidemiological surveys, transmission
      pattern studies, and pilot immunization trials proved the clinical, economic, and
      strategic benefits of mass immunization, thus providing the impetus for the
      implementation of this mass vaccination program. The success of this program has
      led to a decline in hepatitis B carrier rates among children in Taiwan from 10%
      to <1%. Furthermore, the mortality rate of fulminant hepatitis in infants and the
      annual incidence of childhood hepatoma have also decreased significantly in
      recent years. This is one of the most remarkable success stories in the field of
      public health.

PMID- 14731113
TI  - DES2 protein is responsible for phytoceramide biosynthesis in the mouse small
      intestine.
AB  - The C-4 hydroxylation of sphinganine and dihydroceramide is a rate-limiting
      reaction in the biosynthesis of phytosphingolipids. Mouse DES1 (MDES1) cDNA
      homologous to the Drosophila melanogaster degenerative spermatocyte gene-1 (des
      1) cDNA leads to sphingosine Delta4-desaturase activity, and another mouse
      homologue, MDES2, has bifunctional activity, producing C-4 hydroxysphinganine and
      Delta4-sphingenine in yeast [Ternes, Franke, Zahringer, Sperling and Heinz (2002)
      J. Biol. Chem. 277, 25512-25518]. Here, we report the characterization of mouse
      DES2 (MDES2) using an in vitro assay with a homogenate of COS-7 cells transfected
      with MDES2 cDNA and N -octanoyl-sphinganine and sphinganine as substrates. MDES2
      protein prefers dihydroceramide as a substrate to sphinganine, and exhibits
      dihydroceramide Delta4-desaturase and C-4 hydroxylase activities. MDES2 mRNA
      content was high in the small intestine and abundant in the kidney. In situ
      hybridization detected signals of MDES2 mRNA in the crypt cells.
      Immunohistochemistry using an anti-MDES2 peptide antibody stained the crypt cells
      and the adjacent epithelial cells. These results suggest that MDES2 is the
      dihydroceramide C-4 hydroxylase responsible for the biosynthesis of enriched
      phytosphingoglycolipids in the microvillous membranes of intestinal epithelial
      cells.

PMID- 14731112
TI  - Proteasome inhibitors up-regulate haem oxygenase-1 gene expression: requirement
      of p38 MAPK (mitogen-activated protein kinase) activation but not of NF-kappaB
      (nuclear factor kappaB) inhibition.
AB  - Regulation of intracellular protein stability by the ubiquitin-dependent
      proteasome system plays a crucial role in cell function. HO-1 (haem oxygenase) is
      a stress response protein, which confers cytoprotection against oxidative injury
      and provides a vital function in maintaining tissue homoeostasis. In the present
      study, we found a novel action of proteasome inhibitors MG132 and MG262 on HO-1
      induction, and characterized the underlying mechanisms. MG132 (> or =0.1 microM)
      treatment resulted in a marked time- and concentration-dependent induction of the
      steady-state level of HO-1 mRNA in RAW264.7 macrophages, followed by a
      corresponding increase in HO-1 protein. Actinomycin D and cycloheximide inhibited
      MG132-responsive HO-1 protein expression, indicating a requirement for
      transcription and de novo protein synthesis. The involvement of signal pathways
      in MG132-induced HO-1 gene expression was examined using chemical inhibitors.
      Antioxidant N -acetylcysteine and SB203580, an antioxidant and inhibitor of p38
      MAPK (mitogen-activated protein kinase), abolished MG132-inducible HO-1
      expression. Furthermore, MG132 activated the p38 MAPK pathway. The half-life of
      HO-1 protein was prolonged by MG132, indicating that the upregulation of HO-1 by
      proteasome inhibitor is partially attributable to the inhibition of protein
      degradation. MG132 can ablate IkappaBalpha degradation and NF-kappaB (nuclear
      factor kappaB) activation induced by lipopolysaccharide, similar to the effect of
      another NF-kappaB inhibitor pyrrolidine dithiocarbamate. We found HO-1
      upregulation by MG132 and pyrrolidine dithiocarbamate is unrelated to their
      inhibition of NF-kappaB, since leptomycin B, another NF-kappaB inhibitor, did not
      elicit similar induction of HO-1. Taken together, we found a novel effect of
      proteasome inhibitor on induction of HO-1 expression. This action is ascribed to
      the activation of the p38 MAPK pathway, but is not dependent on NF-kappaB
      inhibition.

PMID- 14731120
TI  - Current therapeutic approaches in childhood chronic hepatitis B infection: a
      multicenter study.
AB  - BACKGROUND AND AIM: The aim of the present study was to compare the therapeutic
      efficacy of three different regimens in childhood chronic hepatitis B (CHB)
      infection. METHODS: A total of 182 children with CHB infection were prospectively
      allocated to three random groups. Sixty-two patients in the first group received
      high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months.
      In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months
      (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum
      100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the
      second group, while it was started 2 months prior to IFN injections in the third
      group. RESULTS: The initial mean alanine aminotransferase (ALT) values for the
      first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/-
      42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased
      to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3,
      respectively. The mean ALT value of the first group was significantly different
      to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end
      of the therapy and these differences were found to be sustained after 18 months.
      However, results in the second and third groups were similar (P > 0.05). There
      were no significant differences in HBeAg clearance and anti-HBe seroconversion at
      the initial stage, 12 months and 18 months between the three groups (P > 0.05).
      Hepatitis B virus (HBV) DNA clearance in the first group was different from the
      second and third groups, while the second and third groups had similar HBV DNA
      clearance ratios at 12 and 18 months. No significant difference was found in the
      complete response (normalization of ALT, clearance of HBV DNA and seroconversion
      of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18
      months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05).
      CONCLUSIONS: Although the ALT normalization and HBV DNA clearance ratios of IFN
      plus LAM combination groups were better than the high-dose IFN-alpha monotherapy
      group, no significant difference was found in the complete response ratios of all
      three groups.

PMID- 14731121
TI  - Hepatitis E superinfection produces severe decompensation in patients with
      chronic liver disease.
AB  - BACKGROUND AND AIMS: The adverse effect of acute hepatitis A in chronic liver
      disease is well known. The outcome of acute hepatitis E in chronic liver disease
      has not been extensively studied. The present study aimed to examine the clinical
      profile and outcome of patients with chronic liver disease and hepatitis E virus
      (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in
      patients with chronic liver disease and controls in India. METHODS: A
      retrospective study of patients with chronic liver disease and acute icteric
      hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin
      (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100
      patients with chronic liver disease and 79 age- and sex-matched controls.
      RESULTS: From June 2001 to December 2002, nine patients with chronic liver
      disease were found to have superinfection with HEV. Out of these, six patients
      died of advanced liver failure. The etiology of liver disease was Wilson's
      disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in
      one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for
      HEV in cases and controls, respectively. CONCLUSIONS: Acute HEV in patients with
      chronic liver disease has a grave prognosis. Wilson's disease was the most common
      cause of chronic liver disease complicated by acute HEV. Seroprevalence studies
      showed that 44% of patients with chronic liver disease were at risk of developing
      hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this
      group.

PMID- 14731122
TI  - Fifteen-year follow up of endoscopic injection sclerotherapy in children with
      extrahepatic portal venous obstruction.
AB  - BACKGROUND AND AIM: Endoscopic sclerotherapy has emerged as an effective
      treatment for bleeding esophageal varices both in adults and children but the
      long-term outcome is poorly defined in children. The authors report a 15-year
      follow up of sclerotherapy in children with extrahepatic portal venous
      obstruction. METHODS: Between June 1982 and February 1992, 69 children with
      bleeding esophageal varices underwent sclerotherapy; variceal eradication was
      achieved in 63 (91.3%) patients, with procedure-related morbidity of 28.9% and
      mortality of 1.4%. Fifty-nine patients with variceal eradication were followed
      for between 10.4 and 20.1 years (mean, 15.1 +/- 3.1 years). RESULTS: After a
      median period of 3 years (range, 1.2-12.8 years), seven (11.9%) patients
      presented with recurrent bleeding (esophageal varices, four; gastric varices,
      two; and duodenal ulcer, one). Recurrent bleeding occurred in six of seven
      (85.7%) patients within the first 4 years of initial variceal eradication.
      Esophageal varices recurred in eight (13.6%) patients. Five of the seven patients
      with recurrent bleeding and all eight with recurrent varices were effectively
      treated with further sclerotherapy. Two patients with gastric variceal bleeding
      unresponsive to sclerotherapy underwent shunt surgery. Elective surgery was
      required in eight additional patients for reasons other than recurrent varices or
      bleeding. CONCLUSIONS: The authors conclude that (i) sclerotherapy is the ideal,
      safe and effective treatment for bleeding esophageal varices, that it prevented
      bleeding in 88.1% patients after variceal eradication and hence, should be
      included in primary management strategies; (ii) follow-up endoscopy should be
      performed on a yearly basis for the first 4 years after variceal eradication; and
      (iii) surgery is required as a complementary technique for patients with
      uncontrolled bleeding, painful splenomegaly, growth retardation and symptomatic
      portal biliopathy.

PMID- 14731123
TI  - Increased hepatic and renal expressions of multidrug resistance-associated
      protein 3 in Eisai hyperbilirubinuria rats.
AB  - BACKGROUND AND AIM: Eisai hyperbilirubinuria rats (EHBR) are animal models of
      Dubin-Johnson syndrome, which suffer from jaundice due to impaired biliary
      excretion of bilirubin glucuronides. In EHBR, deficiency of multidrug resistance
      associated protein 2 (mrp2) causes defective biliary excretion of numerous
      organic anions. However, little is known about the expression of other organic
      anion transporters in this mrp2-deficient model. The aim of the present study was
      to investigate adaptive expressions of mrp1, mrp3, mrp6, organic anion
      transporting polypeptide 1 (oatp1) and oatp2 in liver and kidney of EHBR.
      METHODS: For the present study, EHBR (n = 5) were used. Hepatic and renal mRNA
      expression of the aforementioned transporters was determined by constructed
      semiquantitative reverse transcription polymerase chain reaction assay. Their
      protein expression was determined by western blotting. Localization of hepatic
      and renal mrp3 was confirmed by immunohistochemistry. Sprague-Dawley (SD) rats (n
      = 5) were used as normal controls. RESULTS: Deficiency of mrp2 protein was
      confirmed in EHBR. Hepatic and renal expression of mrp3 mRNA was 53.6% (P <
      0.001) and 82.9% (P < 0.001), and its protein expression was 298.9% (P < 0.001)
      and 245.0% (P = 0.001) higher in EHBR than in SD rats, respectively. Hepatic and
      renal expression of mrp1 and mrp6 mRNA was not significantly different between
      EHBR and SD rats. The mrp1 and mrp6 proteins were expressed in very low amounts
      in the liver and kidney of both EHBR and SD rats. In contrast to mrp3, hepatic
      expression of oatp1 and oatp2 mRNA was 33.9% (P = 0. 001) and 38.6% (P < 0.001),
      and their protein expression was 57.4% (P < 0.05) and 51.0% (P < 0.01) lower in
      EHBR than in SD rats, respectively. Hepatic and renal mrp3 protein was localized
      at the basolateral membrane. CONCLUSIONS: Mrp3 plays an important role in the
      compensation of mrp2 deficiency in liver and kidney of EHBR. Hepatic expressions
      of mrp3, oatp1 and oatp2 changed adaptively in this animal model. This is a
      compensatory mechanism for reducing injury to hepatocytes from cytotoxic
      materials that increase in mrp2 deficiency.

PMID- 14731124
TI  - Etiology and outcome of fulminant hepatic failure managed at an Australian liver
      transplant unit.
AB  - BACKGROUND AND AIMS: The primary aims were to identify the incidence, etiology
      and outcome of all adult cases of fulminant hepatic failure (FHF) presenting to
      the Victorian Liver Transplant Unit over the 14 year period since the Unit was
      established in 1988. METHODS: The database of the Unit was used to identify all
      adult patients (>16 years) who were referred to the Austin and Repatriation
      Medical Center in Melbourne with FHF between 1988 and 2001. The Austin and
      Repatriation Medical Center is the sole provider of adult liver transplantation
      services for the states of Victoria and Tasmania. RESULTS: 80 patients (64
      female, 14 male) with FHF were referred, at a rate of approximately one case per
      million population per year. The mean age was 37.6 +/- 13.7 years. Most cases
      were due to either paracetamol poisoning n = 29 (36%) or non-A non-B (idiopathic)
      hepatitis n = 27 (34%). Thirty-five patients were listed for transplantation, of
      which 26 underwent the procedure (77% of transplantation patients currently
      alive). Nine patients were listed for transplantation but did not undergo the
      procedure, eight died before a donor became available and one recovered. Of the
      30 patients who survived without transplantation, 20 cases were due to
      paracetamol poisoning. CONCLUSIONS: Liver transplantation has had a major impact
      on survival of patients with FHF, most significantly in patients with FHF due to
      causes other than paracetamol poisoning, in whom survival without transplantation
      is uncommon. Survival in those who undergo transplantation for FHF is excellent,
      but a significant percentage of patients listed for transplantation die before a
      donor organ becomes available.

PMID- 14731125
TI  - Superoxide and nitric oxide production by Kupffer cells in rats with obstructive
      jaundice: effect of internal and external drainage.
AB  - BACKGROUND AND AIMS: The role of Kupffer cells in obstructive jaundice (OJ) has
      not been fully understood. The aims of the present study were to measure
      superoxide and nitric oxide (NO) production by Kupffer cells in experimental OJ
      in rats and to investigate the response to internal and external biliary
      drainage. METHODS: Eighty male Sprague-Dawley rats were assigned to four groups:
      sham operation, OJ, and internal and external biliary drainage. Kupffer cells
      were isolated on day 7 in the sham operation and OJ group, and on day 7 after
      drainage procedures. Cells were cultured with or without lipopolysaccharide
      (LPS). Superoxide production was quantified in cultured Kupffer cells at 2 h and
      48 h, respectively, after cell isolation using the superoxide dismutase
      inhibitable ferricytochrome c reduction method. Nitrite production in cell
      culture supernatants was measured 48 h later using Greiss reagents. RESULTS:
      Without LPS stimulation, Kupffer cells produced comparable superoxide and nitrite
      in each group (P > 0.05). With LPS stimulation, Kupffer cells in the OJ group
      produced significantly higher superoxide anions than the other groups (P =
      0.006). Nitrite production was significantly increased in the OJ group and
      external biliary drainage group compared to rats in the sham operation and
      internal drainage groups (P < 0.01). CONCLUSIONS: Kupffer cells from rats with OJ
      produce great amounts of endotoxin-mediated oxidants. Both internal and external
      biliary drainage can decrease the elevated superoxide production. Internal
      drainage is superior to external drainage for reversing the distortional capacity
      of NO production by Kupffer cells.

PMID- 14731126
TI  - Lactobacillus plantarum 299: beneficial in vitro immunomodulation in cells
      extracted from inflamed human colon.
AB  - BACKGROUND AND AIM: The present study determined the pattern of cytokine
      secretion (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, interferon
      [IFN]-gamma and IL-10) and their cellular sources in mononuclear cells isolated
      from colonic mucosa from normal and ulcerative colitis (UC) in response to
      probiotic and pathogenic bacteria. METHODS: Mononuclear cells were extracted from
      normal and active UC colonic mucosa and incubated with pure sonicates of
      probiotic, commensal, and pathogenic bacteria. Cytokine secretion was measured in
      culture supernatant and intracellular cytokine staining measured using
      fluorescent-activated cytometry. RESULTS: In mononuclear cells isolated from
      normal mucosa, significant increases in mean IL-1beta were observed with
      enteropathogenic Escherichia coli (286.3 +/- 138.7 pg/mL P < 0.05) and E. coli
      (440.5 +/- 194.0 pg/mL P < 0.01) compared with unstimulated control cells (16.7
      +/- 4.8 pg/mL). In contrast, mononuclear cells isolated from active UC mucosa
      produced significant increases in mean IL-1beta in response to stimulation with
      Salmonella dublin (230.5 +/- 38.8 pg/mL P < 0.05), enteropathogenic E. coli
      (231.7 +/- 45.3 pg/mL P < 0.05) and E. coli (465.4 +/- 60.2 pg/mL P < 0.001)
      compared with unstimulated control cells (60.7 +/- 17.1 pg/mL). Escherichia coli
      also produced significant mean increases of TNF-alpha and IFN-gamma compared with
      unstimulated control cells. No significant increases in IL-1beta, TNF-alpha or
      IFN-gamma were observed with Lactobacillus plantarum in cells derived from normal
      or inflamed mucosa. Strikingly, incubation of L. plantarum with mononuclear cells
      isolated from active UC mucosa resulted in significant increases of mean IL-10
      (327 +/- 53.5 pg/mL, P < 0.05) compared with unstimulated control cells (29.7 +/-
      13.2 pg/mL). Intracellular cytokine staining confirmed T-cell and macrophage IL
      10 production after L. plantarum stimulation. CONCLUSIONS: Lactobacillus
      plantarum demonstrates beneficial immunomodulatory activity by increasing IL-10
      synthesis and secretion in macrophages and T-cells derived from the inflamed
      colon. This may provide a mechanism through which probiotic bacteria ameliorate
      inappropriate inflammation and induce tolerance.

PMID- 14731127
TI  - Hyperexpression of inducible costimulator on lamina propria mononuclear cells in
      rat dextran sulfate sodium colitis.
AB  - BACKGROUND AND AIMS: The authors have previously shown that a third member of the
      CD28 family, inducible costimulator (ICOS), was increased in the inflamed
      intestinal mucosa of murine experimental colitis, and that the blockade of ICOS
      ameliorated the development of colitis. However, the role of ICOS in rat
      intestinal inflammation and its expression profile remains unclear. In the
      present study, the authors investigated the involvement of ICOS in the
      development of rat dextran sulfate sodium (DSS)-induced colitis, and the
      therapeutic potential of anti-ICOS monoclonal antibody (mAb) in colitis. METHODS:
      The authors first examined expression of ICOS protein in normal rat by
      immunohistochemistry and flow cytometry. Sprague-Dawley rats were fed 3.0% DSS.
      The expression of ICOS on infiltrating lamina propria mononuclear cells and
      splenocytes were examined. The DSS-fed rats were then administered anti-ICOS mAb
      to test its effect on the development of colitis. RESULTS: Unlike mice and human,
      ICOS was expressed on a part of CD4+ T-cells from the thymus, spleen, mesenteric
      lymph nodes and lamina propria. Levels of ICOS on CD4+ T-cells from the spleen
      and colonic lamina propria were significantly upregulated after Concanavalin A
      (Con A) stimulation. In addition, ICOS was also upregulated on CD4+ T-cells from
      DSS-fed rats compared with those from non DSS-fed rats. However, anti-ICOS mAb
      did not ameliorate the development of both acute and chronic DSS colitis.
      CONCLUSION: These results suggest that the different expression of ICOS in rats
      plays a distinct role in rat intestinal inflammation.

PMID- 14731128
TI  - Clinical usefulness of carbohydrate antigen 19-9 as a screening test for
      pancreatic cancer in an asymptomatic population.
AB  - BACKGROUND AND AIM: Although the prognosis for pancreatic cancer is generally
      poor, it is well known that the survival rate for resected pancreatic cancer is
      much higher than that for more conservative treatment. The importance of early
      detection is emphasized for resection of pancreatic cancer. Measurement of serum
      carbohydrate antigen (CA) 19-9 has shown satisfactory sensitivity and predictive
      value in symptomatic patients, but no available data has been found on healthy
      asymptomatic subjects. Thus, the authors aimed to determine the clinical
      usefulness of CA 19-9 as a screening tool for pancreatic cancer in asymptomatic
      subjects. METHODS: From December 1994 to November 2000, 70 940 asymptomatic
      persons visiting the Health Promotion Center at the Samsung Medical Center,
      Seoul, Korea, participated. All subjects underwent abdominal ultrasonography and
      serum CA 19-9 measurement. The authors analyzed the sensitivity, specificity, and
      predictive values of CA 19-9 for detecting pancreatic cancer. Also, those
      subjects who had a serum CA 19-9 level above the cut-off value were followed up
      using a serial check of CA 19-9, computed tomography, or endoscopic retrograde
      cholangiopancreatography. RESULTS: The number of subjects with a level of CA 19-9
      above the cutoff of 37 U/mL was 1063 (1.5%), including four cases diagnosed with
      pancreatic cancer. The prevalence of pancreatic cancer over the age of 30 years
      is 13.66 per 100 000 population in Korea. Therefore, the sensitivity is 100% and
      the specificity 98.5%. However, the positive predictive value of CA 19-9 for
      detecting pancreatic cancer is only 0.9% in the asymptomatic population.
      CONCLUSION: Mass screening for pancreatic cancer using CA 19-9 levels in
      asymptomatic subjects is ineffective because of a very low positive predictive
      value, despite its high sensitivity and specificity.

PMID- 14731129
TI  - Visceral perception thresholds after rectal thermal and pressure stimuli in
      irritable bowel syndrome patients.
AB  - BACKGROUND AND AIM: Visceral hypersensitivity has been shown to be present in
      irritable bowel syndrome (IBS). The current study sought to compare the
      characteristics of visceral perception thresholds after rectal thermal and
      pressure stimuli between IBS patients and healthy subjects. METHODS: A total of
      46 patients with IBS were diagnosed using Rome II criteria. Thirteen healthy
      individuals participated in the study. Rectal visceral perception thresholds were
      examined in patients with IBS and in normal controls after thermal and pressure
      stimuli. Subjects were asked to report the sensation type, location, and spread.
      RESULTS: Compared with healthy subjects, IBS patients demonstrated significantly
      initially lower perception thresholds and defecation thresholds to rectal thermal
      and pressure stimuli, particularly in patients with diarrhea-predominant IBS. Ice
      stimuli on the abdominal wall had varied effects on symptoms in patients with IBS
      and did not affect perception thresholds. CONCLUSIONS: Visceral perception
      thresholds were decreased significantly after rectal thermal and pressure stimuli
      in patients with IBS. Visceral hypersensitivity may be one of the important
      pathogenic mechanisms in IBS.

PMID- 14731130
TI  - Cost of outpatient care in patients with inflammatory bowel disease in a German
      University Hospital.
AB  - BACKGROUND AND AIM: Because of its long duration, inflammatory bowel disease
      (IBD) causes high use of health services and high lifetime costs for medical
      care. The aim of the present study was to measure the costs of outpatient care in
      patients with IBD in a German University Hospital and to identify potentially
      relevant determinants of costs. METHODS: The use of resources of 599 outpatient
      patients treated at a German University Hospital (65% Crohn's disease [CD] and
      26% ulcerative colitis [UC]) was measured using a routine database. Costs of
      medical services (diagnostics and treatment) were considered as well as costs of
      medication. Resource use was valued using fee schedules for hospital services and
      pharmacy prices for drugs. RESULTS: The mean cost of one outpatient visit was
      Euros 162, including physician costs, laboratory costs, and costs of diagnostic
      procedures following the visit. For a subgroup of 272 patients, the mean annual
      cost for outpatient care was Euros 3171. Medication accounted for 85% of the
      total annual costs. Potential determinants, such as main diagnosis (CD or UC),
      sex, age, localization of disease, and occurrence of anemia, had no influence on
      costs, whereas complications of IBD and use of corticosteroids showed an impact
      on annual costs. CONCLUSIONS: This is the first time that the structure and range
      of outpatient treatment costs for IBD have been demonstrated for a German
      hospital.

PMID- 14731131
TI  - Helicobacter pylori is a fragile bacteria when stored at low and ultra-low
      temperatures.
AB  - BACKGROUND AND AIM: Usually, bacteria are cryopreserved for short-term storage at
      low and ultra-low temperatures. There are no reports as to whether Helicobacter
      pylori is a fragile bacteria when stored at low and ultra-low temperatures as
      compared with other intestinal bacteria. A study was done on seven H. pylori
      strains and other intestinal bacteria to compare different temperatures for
      storage of organisms in saline solution. METHODS: Seven H. pylori strains,
      specifically American Type Culture Collection (ATCC) strains 43504 and TN2GF4,
      and five strains isolated from the present patients were grown on a modified
      Skirrow's agar for H. pylori. Escherichia coli and Bacteroides distasonis, both
      representing isolates from the present patients, were grown on trypticase soy
      blood agar for E. coli, and EG agar for B. distasonis. Culture was for 4-5 days
      under microaerobic, aerobic and anaerobic conditions at 37 degrees C. Cells were
      harvested by scraping growth from the solid medium and into sterile saline. The
      cells were adjusted to concentrations of 109 viable cells/mL in saline and
      preserved at 4 degrees C, -20 degrees C, or -80 degrees C for 3 weeks before
      reculture under microaerobic, aerobic and anaerobic conditions at 37 degrees C
      for 7 days. After incubation, morphologically distinct colonies were counted,
      isolated, and identified by standard bacteriologic techniques. The H. pylori were
      morphologically analyzed by electronic microscopy before and after preservation.
      Mongolian gerbils were inoculated with the cryopreserved H. pylori to evaluate
      the bacterial infectivity. RESULTS: Six of the seven H. pylori strains failed to
      culture after being preserved at 4 degrees C, -20 degrees C, or -80 degrees C.
      Only ATCC 43504 could be cultured after freezing at -80 degrees C. The number of
      H. pylori ATCC 43504 before preservation was 9.0 +/- 0.5 (log10 no. organisms/mL)
      and decreased to 5.7 +/- 0.6 after preservation. Morphologically, all H. pylori
      except ATCC 43504 strains transformed from a bacillary to a coccoid form after
      preservation. In addition, none of the H. pylori strains could infect Mongolian
      gerbils after preservation. Escherichia coli and B. distasonis were recovered.
      Titers before and after 4 degrees C, -20 degrees C, and -80 degrees C,
      respectively, were 9.1 +/- 0.2, 8.9 +/- 0.5, 8.6 +/- 0.3, and 8.7 +/- 0.3 for E.
      coli and 9.1 +/- 0.4, 8.7 +/- 0.6, 8.6 +/- 0.5, and 8.8 +/- 0.3 for B.
      distasonis. CONCLUSIONS: Helicobacter pylori is a fragile bacteria for storage at
      low and ultra-low temperatures in comparison with other intestinal bacteria.

PMID- 14731132
TI  - Electric activity of the colon in irritable bowel syndrome: the 'tachyarrhythmic'
      electric pattern.
AB  - BACKGROUND AND AIM: The etiology of irritable bowel syndrome is unknown. It
      presents with crampy abdominal pain associated with alternating constipation and
      diarrhea but with no anatomic abnormality on diagnostic testing. Because the
      condition is related to motility disturbance, the hypothesis that a disorder of
      the colonic electromyographic activity is responsible for the colonic motile
      disorders in irritable bowel syndrome, was investigated. METHODS: The
      electromyographic activity of the sigmoid colon was recorded transcutaneously in
      18 patients with irritable bowel syndrome (49.6 +/- 10.2 years, 12 women) and 14
      healthy volunteers (47.2 +/- 9.9 years; eight women) by applying three electrodes
      to the abdominal skin below the umbilicus. The sigmoid colon pressure was
      measured by means of a saline-perfused tube connected to a pneumohydraulic
      capillary infusion system. RESULTS: Slow waves with a regular rhythm were
      recorded in the healthy volunteers exhibiting the same frequency, amplitude and
      conduction velocity from all three electrodes. Action potentials (AP) were not
      registered. The basal sigmoid colon pressure was interrupted by bouts of
      elevation. In irritable bowel syndrome, the electromyographic rhythm was
      irregular and the slow wave variables were higher than those of the normal
      volunteers and were not the same from the three electrodes; occasional AP were
      also recorded. The sigmoid colon basal pressure was significantly higher, and was
      interrupted by pressure bouts significantly higher, than those of the volunteers.
      CONCLUSIONS: Irritable bowel syndrome exhibited a 'tachyarrhythmic' pattern of
      electromyographic activity with higher slow wave variables than normal and
      occasional AP. The resulting elevated basal colonic pressure and tone may explain
      some of the irritable bowel syndrome symptoms. Because diagnostic testing of the
      irritable bowel syndrome shows no anatomic abnormalities, it is suggested that
      the cause of irritable bowel syndrome is related to an abnormal focus in one or
      more of the colonic pacemakers emitting these abnormal waves. However, further
      studies are required to verify these findings.

PMID- 14731133
TI  - Novel human, mouse and xenopus genes encoding a member of the RAS superfamily of
      low-molecular-weight GTP-binding proteins and its downregulation in W/WV mouse
      jejunum.
AB  - BACKGROUND AND AIM: Interstitial cells of Cajal (ICC) are pacemakers and
      mediators of neurotransmission in gastroenteric smooth muscles. Interstitial
      cells of Cajal require cellular signaling via KIT, a receptor tyrosine kinase,
      for development and maintenance of cellular phenotype. Much of the evidence
      demonstrating the functions of ICC comes from studies of W/W V mutant mice, which
      have reduced KIT function. The aim of the present study was to differentially
      examine gene expression in the small intestines of wild-type and W/W V mice.
      METHODS: RNA from the jejunum of wild-type and W/W V mice was analyzed using a
      differential gene display method. RESULTS: One candidate gene, encoding a novel
      small GTPase of the RAS superfamily, was significantly suppressed both in fed and
      starved W/WV mice. The full-length clone of the murine gene and its human and
      xenopus counterparts were designated GTP-binding protein, 28 kDa (G28K). Human
      G28K cDNA encodes a protein of 258 amino acids with homology to the human cell
      division cycle 42/G25K protein. This gene is located at 1q42.11-q42.3. G28K was
      abundantly expressed in the human stomach and the small intestine. Semi
      quantitative reverse transcription-polymerase chain reaction analysis revealed
      expression of G28K mRNA within single isolated ICC. CONCLUSIONS: Gene analysis
      showed that G28K was differentially expressed in the small intestines of wild
      type and W/W V mice. Interstitial cells of Cajal within the small intestine
      expressed mRNA for G28K. The specific downregulation of G28K in the jejunum of
      W/W V mice, and high expression in human intestinal tissue suggest that the G28K
      gene might be associated with ICC function in mice and in humans.

PMID- 14731134
TI  - Downregulation of gelsolin and retinoic acid receptor beta expression in gastric
      cancer tissues through histone deacetylase 1.
AB  - BACKGROUND AND AIM: Overexpression of histone deacetylase (HDAC)1, which controls
      the expression of genes related to cell cycle and apoptosis, has recently been
      reported in gastric cancer (GC) tissues. In the present study, the pattern of
      gelsolin and retinoic acid receptor (RAR)beta expression in GC tissues showing
      HDAC1 overexpression was investigated. METHODS: Expression profiles of HDAC1,
      gelsolin, and RARbeta were evaluated and compared using reverse transcription
      polymerase chain reaction, immunoblotting, and immunohistochemical analyses with
      22 paired primary human GC tissues and corresponding normal tissues. RESULTS:
      Compared with normal gastric tissue, increased expression of HDAC1 mRNA and
      protein was detected in 17 (77.3%) of 22 GC tissues, while decreased expressions
      of gelsolin mRNA and protein were shown in 15 (68.1%) samples. Concomitantly,
      expressions of RARbeta mRNA and protein were decreased in 16 (72.7%) and 17
      (77.3%), respectively. Among 17 GC tissues with increased HDAC1 expression, the
      expressions of gelsolin and RARbeta were simultaneously decreased in 14 (82.4%)
      and 15 (88.2%) GC tissues, which indicates a strong inverse correlation between
      HDAC1 and gelsolin/RARbeta expressions. Correlation between HDAC1 and
      gelsolin/RARbeta was also confirmed by immunohistochemistry. CONCLUSIONS: Taken
      together, the results of the present study reveal that silencing of gelsolin and
      RARbeta occurs in GC tissues probably through HDAC1 overexpression and might play
      some role in gastric carcinogenesis.

PMID- 14731135
TI  - Gastrointestinal: cecal volvulus.

PMID- 14731136
TI  - Gastrointestinal: Gastric diverticula.

PMID- 14731137
TI  - CFTR gene and cystic fibrosis.

PMID- 14731138
TI  - Paraduodenal hernia and jejunal diverticulosis.
AB  - A case of left-sided paraduodenal hernia and jejunal diverticulosis is described
      in 75-year-old man who presented with chronic intermittent abdominal pain, weight
      loss, and anemia. A brief review of the epidemiology, pathogenesis, and clinical
      presentation displays the variety of symptoms associated with these rare
      conditions.

PMID- 14731139
TI  - Not all hepatic carcinoids are metastases.

PMID- 14731140
TI  - Double gallbladder.

PMID- 14731141
TI  - Acute neoplastic obstruction of the splenic flexure: effective presurgical
      palliation with a biliary metallic stent.

PMID- 14731142
TI  - Corticosteroids and lamivudine combined to treat acute severe flare-up in a
      chronic hepatitis B and C patient.

PMID- 14731143
TI  - Liver cirrhosis observed in a patient with chronic excessive menthol intake.

PMID- 14731144
TI  - Easy ultrasound detection of retained video endoscopy capsule.

PMID- 14731146
TI  - Equity and need when waiting for total hip replacement surgery.
AB  - OBJECTIVES: To explore sociodemographic and health status factors associated with
      waiting times both for first outpatient appointment and for total hip replacement
      surgery (THR). METHODS: A survey of THR in five former English regions was
      conducted between September 1996 and October 1997. Every patient listed for THR
      was asked to fill out a questionnaire preoperatively. This questionnaire included
      the 12-item Oxford Hip Score (OHS) questionnaire and two questions on the length
      of time patients waited for an outpatient appointment and subsequently for their
      operation. RESULTS: From multiple logistic regression analyses, region, private
      vs. public sector, housing tenure and preoperative OHS were all independently
      associated with a waiting time for an outpatient appointment for > 3 months.
      Region, housing tenure and gender were also independently associated with a wait
      of >or= 6 months on the surgical waiting list. CONCLUSIONS: A large proportion of
      patients had long waiting times both for an outpatient appointment and while on a
      surgical waiting list. There were significant differences in waiting time
      according to social, geographical and health care system factors. Patients with a
      worse pain and disability at surgery waited longer for an outpatient appointment.
      The longer patient waited, the worse was their pain and disability, suggesting
      that patients were not prioritized by these criteria. Benefits of prioritizing
      should be tested.

PMID- 14731147
TI  - Electronic Clinical Communications Implementation (ECCI) in Scotland: a mixed
      methods programme evaluation.
AB  - AIMS: The Electronic Clinical Communications Implementation programme aims to
      facilitate implementation of electronic systems for primary-secondary care
      communication, focusing on laboratory results reporting, outpatient appointment
      booking, referral, discharge and clinic correspondence, and clinical e-mail. This
      independent programme evaluation explored the processes and outcomes of
      implementation, barriers and facilitators to system adoption, and benefits and
      drawbacks for professional users. METHODS: The mixed methods approach
      incorporated document review, surveys, stakeholder interviews, consensus
      exercises, and monthly recording of quantitative process and outcome variables.
      RESULTS: Qualitative and survey work highlighted wide variation in the
      technologies and implementation approaches adopted. A consensus process was used
      to instigate a national minimum dataset. To date, implementation of laboratory
      results reporting has demonstrated the greatest success and electronic outpatient
      booking the least. A mixed-format survey of users in clinical practice revealed a
      more detailed picture of behaviour and attitudes demonstrating that where systems
      are available and accepted they are utilized, while product usability, process
      complexity and user-engagement methods influence uptake. CONCLUSIONS: The
      evaluation has demonstrated the difficulties faced when attempting to implement a
      multifaceted technological and behavioural change intervention on a national
      scale, but has also revealed unexpected benefits, including general improvements
      in Information Management & Technology capability across the Scottish health
      service.

PMID- 14731148
TI  - Patient experience of time duration: strategies for 'slowing time' and
      'accelerating time' in general practices.
AB  - Approaches to time management in general practices characteristically focus on
      objective 'clock time', for example, through appointment scheduling. No less
      important, however, is how patients experience time duration. Time is experienced
      as having passed slowly (time prolongation), quickly (time compression) or in
      rough synchronization with clock time. Duration has been theorized to be
      positively associated with information processing. This paper builds on that
      theory to suggest how practices can influence patients' subjective experience of
      duration in the practice environment, for example, by making waiting times appear
      to quicken and consultations appear to slow.

PMID- 14731149
TI  - Mental Health Link: the development and formative evaluation of a complex
      intervention to improve shared care for patients with long-term mental illness.
AB  - AIMS AND OBJECTIVES: This study aims to develop an intervention and related
      conceptual framework for developing shared care for patients with long-term
      mental illness, and to provide a case study of the development of a complex
      intervention in primary care. METHODS: A pragmatic iterative design involved a
      literature review and focus groups followed by a formative evaluation including
      reflection, questionnaires and interviews. General practices and associated
      community mental health teams in Southeast London were involved. Participants
      included community mental health workers, psychiatrists, practice nurses, general
      practitioners, managers and local experts with an interest in primary mental
      health care. RESULTS: The model for shared care includes the core components of
      improved communication together with the development of a register and database
      with systems for review and recall. Local needs assessment, audit, training and
      guidelines are complimentary components. The intervention, Mental Health Link, is
      a facilitated quality improvement programme which aims to expedite the
      development of services by bringing the teams together to agree on a model of
      shared care suited to local needs, skills and interests, and by supporting the
      development of practice systems. CONCLUSIONS: A model for shared care needs to
      take into account interdependencies of the components as well as the relationship
      with the context. The heterogeneity of primary and community care need to be
      reflected in the development of complex interventions designed to enhance shared
      care. It is possible to develop a generalizable complex intervention which is
      sensitive to local circumstances.

PMID- 14731150
TI  - Strategies for ensuring effective surveillance in post-transplant patients:
      practical organization and clinical evaluation.
AB  - Results of renal transplantation have improved steadily over the years. This
      article reviews the current status of patient and graft survival and discusses
      major causes of mortality and renal allograft failure. Review of recent
      literature demonstrates that the traditional enemies of transplantation, acute
      rejection and opportunistic infections are no longer major problems facing
      transplantation. Chronic graft nephropathy and death with functioning graft due
      to cardiovascular disease are the main challenges in the current era. An impact
      of an early graft thrombosis, recurrent renal disease and post-transplant
      malignancies are also reviewed. Chronic graft nephropathy is examined in a
      context of differences between two calcineurin inhibitors, cyclosporin
      microemulsion and tacrolimus. Strategies of post-transplant surveillance are
      suggested.

PMID- 14731151
TI  - Emergency department mental health triage scales improve outcomes.
AB  - The assessment and management of clients with mental illness is an important
      facet of providing emergency care. In Australian emergency departments, it is
      usually the generalist registered nurses* without adequate preparation in the
      assessment and care for clients with mental illness who conduct the initial
      assessment at triage. A search of the literature revealed a limited number of
      publications addressing the provision of triage and management guidelines to
      assist nurses to make objective clinical decisions to ensure appropriate care for
      clients with mental illness. This paper examines the need for such guidelines and
      reviews a number of mental health triage scales that have been evaluated for use
      in emergency departments. Findings show that these triage scales have led to
      improvements in staff confidence and attitudes when dealing with clients with
      mental health problems, resulting in improved outcomes for clients. Strengths and
      limitations of the evaluations have also been explored. Highlighted is the need
      for consideration of the inclusion of clients' reactions to the impact of this
      change to service delivery in future evaluations.

PMID- 14731152
TI  - Capturing lay perspectives in a randomized control trial of a health promotion
      intervention for people with osteoarthritis of the knee.
AB  - Osteoarthritis (OA) is a common and often disabling condition that predominately
      affects older adults. It is the commonest cause of locomotor disability and forms
      a major element of the workload in primary care. Previous studies suggest that
      there are both deficits in the knowledge patients have about their disease and
      extensive 'unmet' information needs. This paper explores the patients'
      perspective on the meaning and significance of living with arthritis, identified
      through quantitative and qualitative approaches undertaken during a trial that
      evaluated the effectiveness of a primary care-based patient education programme.
      This paper draws on qualitative and quantitative data from: the baseline
      interview (knowledge of arthritis, satisfaction with services and support
      received in primary care); patient diaries (individual goals and reflections on
      treatment); and group teaching sessions (themes describing the patient's
      experience). The different data sources were interrogated for common and
      divergent themes. One hundred and ninety-four participants were identified and
      170 completed baseline interviews. Participants were predominantly female (73%),
      with a mean age of 63 and arthritis of long-standing; 55% reported that they had
      had it for 5 years or more. Use of primary care services was high, with 41%
      consulting their GP in the 2 weeks before interview. Levels of information were
      low, with less than 25% receiving support/advice about the disease, pain
      management or its impact upon daily life. Set against negative perceptions of the
      quality of services, patients' personal priorities were for improved pain
      management and enhanced mobility/functional ability. The combined quantitative
      and qualitative data provide insight into the patients' perspective on the causes
      and impact of knee OA, individual goals desired from treatment and the quality of
      care. There is consistent evidence of unmet needs for information and support and
      the priority placed by patients on finding strategies to cope with OA and
      maintaining independence. Even within a tightly defined study sample
      participating in the intervention, a diversity of experience and goals were
      revealed, which highlights the importance of taking account of contextual factors
      and individual differences when evaluating complex interventions.

PMID- 14731153
TI  - Whither bioethics? A reply to commentaries on 'the rationale of value-laden
      medicine' (Kottow 2002; Journal of Evaluation in Clinical Practice 8, 77-84).

PMID- 14731155
TI  - Cognitive factors in student nurses' clinical problem solving.
AB  - RATIONALE, AIMS AND OBJECTIVES: The assumption that the acquisition and mastery
      of the nursing process alone is sufficient to explain problem-solving performance
      has been challenged in recent literature. Researchers have argued that the
      quality of prior knowledge is a key component in explaining performance. In
      addition, motivational orientation and the quality of reasoning have been found
      to have different effects on performance in cognitive tasks. The aim of this
      study is to explore student nurses' clinical problem solving based on a model
      consisting of their motivational orientation, prior knowledge, diagnostic
      reasoning and diagnostic solutions. METHODS: One hundred and thirty-five second
      year nursing students completed the Study Process Questionnaire and the Causal
      Attribution Questionnaire prior to receiving five lectures on mental illness. A
      knowledge test and a clinical problem-solving task provided measures of prior
      knowledge, quality of diagnostic reasoning, and the quality and comprehensiveness
      of nursing diagnosis. A correlational design using pairwise correlations,
      hierarchical regression and path analysis examined the relationships among these
      data. RESULTS AND CONCLUSIONS: The results indicated an important role for a
      belief in personal control, for the accessibility and structuring of prior
      knowledge, and the quality of diagnostic reasoning, in generating high quality
      and comprehensive nursing diagnoses. The findings suggest that all contributing
      components of clinical problem solving need to be addressed in nursing education.

PMID- 14731156
TI  - Change, humanity, and the nature of exile: workforce planning and the future of
      the health service.
AB  - There have been many changes in the practice of medicine in the UK in the recent
      past, including major changes in training and trainees' hours, treatment options
      and patient expectations. These, in combination with a need for better
      accountability and improved continuing medical education, have increased the
      demands on senior doctors, and made apparent the need for increased medical
      resource. There would seem to be four areas through which this is being addressed
      - increased production of doctors; changes in medical training; changes in
      medical practice, and retention of seniors in post. This paper examines some of
      the perceived advantages and potential disadvantages of these approaches. It
      concludes that if the health service is to have a viable long-term future, its
      survival in the short term depends on maintaining within the service the skills
      of those seniors who have borne the brunt of recent change.

PMID- 14731157
TI  - Predictors of HIV/AIDS among individuals with tuberculosis: health and policy
      implications.
AB  - The purpose of this report was retrospectively to assess the application of
      clinical predictors (i.e. signs and symptoms) for the diagnosis of the human
      immunodeficiency virus (HIV) infections, including the acquired immunodeficiency
      syndrome (AIDS), among tuberculosis (TB)-positive subjects enrolled within an
      urban heterosexual sero-discordant couple (one partner HIV-positive and the other
      HIV-negative) cohort study at an HIV prevention and research centre in Lusaka,
      Zambia. Available medical, clinical and laboratory records from 1994 to mid-1998
      were reviewed, with follow-up visits to the local chest clinics and sputum
      analyses laboratories instituted as additional quality assurance measures. A
      nested case-control study was employed. The World Health Organization clinical
      case definition for HIV/AIDS (WHOCCDA) was observed to be significantly more
      likely to predict HIV/AIDS among TB-positive HIV-positive subjects than TB
      positive HIV-negative subjects. Therefore, this report documents the relative
      effectiveness of the WHOCCDA in predicting HIV/AIDS cases and discusses the
      health and policy implications, especially for the developing world which
      accounts for a significant proportion and impact of HIV/AIDS. Further research
      studies based on prospective randomized controlled trails or other rigorous
      evaluation strategies are warranted to substantiate these findings.

PMID- 14731158
TI  - Evaluating the treatment of hypertension in diabetes mellitus: a need for better
      control?
AB  - OBJECTIVES: To determine how well and to what extent blood pressure (BP) is
      controlled in diabetic hypertensive patients treated by primary care doctors, and
      to evaluate drug therapy in the backdrop of risk factors and laboratory findings.
      METHODS: A therapeutic audit of the medical records of diabetic hypertensives
      from nine primary care health centres in Bahrain. RESULTS: In 266 diabetic
      hypertensives (82 males and 184 females), the recommended target BP < 130/< 85
      mmHg (WHO/ISH guidelines, 1999) was achieved in 20 (9.8%) with a BP of 119 +/-
      4/76 +/- 5 mmHg. Among those who did not achieve target BP, 70 (34.5%) lacked
      systolic BP control (BP = 153 +/- 17/79 +/- 3 mmHg), four (2%) lacked diastolic
      BP control (BP = 123 +/- 3/86 +/- 3 mmHg) and 109 (53.7%) lacked both systolic
      and diastolic BP control (BP = 158 +/- 20/94 +/- 7 mmHg). The mean age of the
      group achieving target BP was significantly lower than the group which lacked
      systolic BP control (51.6 +/- 9 vs. 63.5 +/- 9 years; P < 0.0001). While there
      were no significant differences in fasting blood glucose, glycosylated
      haemoglobin, triglycerides, urea, creatinine, uric acid and serum electrolytes
      between the group achieving target BP vs. groups without target BP, a significant
      difference in total cholesterol was seen. PATIENTS: with ischaemic heart disease
      and/or isolated systolic hypertension did not achieve the target BP.
      Antihypertensive monotherapy was prescribed in 145 (54.5%) patients, whereas two-
      and three-drug combinations were prescribed in 32.3 and 8.2% of patients,
      respectively. As monotherapy, angiotensin-converting enzyme (ACE) inhibitors were
      the most frequently prescribed drugs followed by beta-blockers, calcium channel
      blockers (CCBs) and diuretics. As two-drug combinations, an ACE inhibitor with a
      beta-blocker/diuretic and a beta-blocker with a CCB/diuretic were usually
      prescribed. CONCLUSIONS: According to the WHO/ISH 1999 guidelines, approximately
      one out of 10 diabetic hypertensives achieved target BP control. In many
      instances, the drug therapy prescribed was inappropriate considering the
      comorbidity in patients and their laboratory findings. Improved BP control is
      needed in treating high-risk groups such as patients with diabetes mellitus, and
      efforts should be made to improve the treatment of hypertension in the primary
      care setting.

PMID- 14731159
TI  - Audit: internet awareness and use amongst general orthopaedic outpatients.

PMID- 14731162
TI  - Risk factors and occurrence of rash in HIV-positive patients not receiving
      nonnucleoside reverse transcriptase inhibitor: data from a randomized study
      evaluating use of protease inhibitors in nucleoside-experienced patients with
      very low CD4 levels (<50 cells/microL).
AB  - BACKGROUND: Most of the studies evaluating rash in HIV-positive patients have
      focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly
      nevirapine, and little is known about the occurrence of rash and the risk factors
      for its development in patients receiving regimens not based on NNRTI. METHODS:
      We evaluated all cases of rash observed during a 48-week randomized multicentre
      trial in 1251 nucleoside-experienced patients who started treatment with protease
      inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/microL.
      Incidence rates for rash were calculated according to gender, clinical status,
      age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii
      pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at
      enrollment. Differences between groups defined according to the above
      characteristics were tested for statistical significance using the log-rank test
      in a Kaplan-Meier survival analysis. All factors that gave results in the
      univariate analyses below the significance level of 0.05 were included in a
      multivariate analysis using a Cox regression model. RESULTS: During a follow-up
      period of 9690 person-months, 66 patients (5.3%) developed rash (0.68 events/100
      person-months). In the univariate analyses, risk of rash did not differ with
      trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or
      age. During follow-up, rash was observed in 7.5% of enrolled women and in 4.5% of
      enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in
      1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of
      zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be
      associated with a lower risk of rash. In the multivariate analysis, the variables
      that remained significantly predictive of rash were gender (risk for women
      compared to men: 1.65, 95% confidence interval (CI): 1.00-2.72, P=0.048) and use
      of a non-HAART regimen (risk for non-HAART patients compared to HAART: 2.73, 95%
      CI: 1.49-5.02, P=0.001). CONCLUSIONS: In our study, about 5% of HIV-positive
      patients who started treatment with protease inhibitors at very low CD4 counts
      developed rash, generally in the first few weeks after treatment. Risk was
      significantly higher in women and in patients who did not receive a HAART
      regimen. Our data indicate that women have a higher risk of rash than men, also
      with regimens that do not include NNRTI.

PMID- 14731163
TI  - Greater and more rapid depletion of mitochondrial DNA in blood of patients
      treated with dual (zidovudine+didanosine or zidovudine+zalcitabine) vs. single
      (zidovudine) nucleoside reverse transcriptase inhibitors.
AB  - BACKGROUND: Most toxicities associated with nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) are thought to result from mitochondrial
      toxicity. These toxicities include peripheral neuropathy, pancreatitis, lactic
      acidosis, and peripheral lipoatrophy. Unfortunately, there are no validated
      laboratory markers for clinically assessing, let alone predicting, the onset of
      mitochondrial toxicity associated with NRTI therapy. OBJECTIVES: To provide
      preliminary evidence of the potential clinical utility of an assay which has been
      developed for quantifying mitochondrial DNA (mtDNA) in clinical samples from HIV
      infected patients. METHODS: A single-tube duplex real-time DNA-nucleic acid
      sequence-based amplification (NASBA) assay (Mitox, Primagen, Amsterdam, the
      Netherlands) was used to quantify mtDNA in cryopreserved peripheral blood
      mononuclear cells (PBMC) obtained from HIV-1-infected patients during their prior
      participation in a randomized placebo-controlled trial comparing zidovudine (ZDV)
      monotherapy with combinations of ZDV plus either dideoxycytidine (ddC) or
      didanosine (ddI) (the Delta trial). Patients were antiretroviral naive prior to
      entering the trial. Samples obtained during the initial 48 weeks of treatment
      were tested. RESULTS: A significant decline of mtDNA, both in an intent-to-treat
      and in an as-treated analysis, was observed in patients treated with ZDV+ddC and
      ZDV+ddI, but not with ZDV alone, consistent with the results expected from the
      degree of mtDNA depletion described for each of these drugs in vitro.
      CONCLUSIONS: This single-tube duplex real-time DNA-NASBA assay was shown to
      measure mtDNA accurately in PBMC. Treatment with a combination of two NRTIs was
      associated with greater reductions in mtDNA than obtained for ZDV monotherapy.
      The relevance of these results in predicting treatment toxicity requires further
      evaluation.

PMID- 14731164
TI  - A prospective, controlled study assessing the effect of lopinavir on amprenavir
      concentrations boosted by ritonavir.
AB  - In a controlled, prospective study, the efficacy of ritonavir 200 mg twice daily
      (bid) in inhibiting the decrease of amprenavir plasma concentrations caused by co
      administration of lopinavir was assessed. Twelve HIV-seropositive patients were
      enrolled, and nine patients completed the 28-day study. At day 14, plasma
      concentrations of amprenavir 600 mg bid and ritonavir 200 mg bid were determined
      over 12 h. At day 15, lopinavir 400 mg bid was added. At day 28, plasma
      concentrations of amprenavir, ritonavir and lopinavir were assessed. Co
      administration of lopinavir was found to decrease the amprenavir concentration,
      determined as the median area under the curve over 12 h (AUC12), by 25% (AUC12
      24.9 microg/h/mL vs. 18.5 microg/h/mL; P<0.01), despite the presence of ritonavir
      200 mg bid. Eight participants discontinued the study regimen during the first 6
      weeks because of adverse gastrointestinal events. In conclusion, gastrointestinal
      tolerance of a regimen containing an increased dose of ritonavir 200 mg bid was
      low, while the regimen did not prevent a decrease of amprenavir and possibly
      lopinavir plasma concentrations.

PMID- 14731165
TI  - Increased microvascular network in bone marrow of HIV-positive haemophilic
      patients.
AB  - OBJECTIVES: Angiogenesis has been associated with the pathogenesis of
      myelodysplastic syndromes (MDSs). However, less is known about the significance
      of this process in the bone marrow of HIV-positive patients with myelodysplastic
      features (MDF). METHODS: Trephines from 22 HIV-positive haemophilic patients were
      immunostained for CD34 antigen, and the microvessel density (MVD) was
      quantitatively evaluated and compared with that of 21 biopsies from patients with
      primary MDS and with that of 12 control bone marrows with no evidence of marrow
      disease. RESULTS: Bone marrow MVD in HIV-positive haemophilic patients was
      similar to that in patients with MDS; however, both groups revealed significantly
      higher MVD counts than those of control bone marrows (P=0.002). Mean MVD counts
      of HIV-positive haemophilic patients were significantly associated with HIV RNA
      levels (P=0.008). In contrast, no correlation was found between MVD and clinical
      HIV stage or CD4 counts at the time of biopsy. CONCLUSIONS: These results suggest
      a direct involvement of HIV in the pathogenesis of MDF in HIV infection.
      Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive
      patients may provide further insights into the pathobiology of AIDS.

PMID- 14731166
TI  - Treatment of primary HIV-1 infection with nonnucleoside reverse transcriptase
      inhibitor-based therapy is effective and well tolerated.
AB  - OBJECTIVES: Highly active antiretroviral therapy (HAART) has been advocated for
      the management of primary HIV-1 infection. We investigated the use of a
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in this
      setting. METHODS: Twenty-one antiretroviral-naive individuals with early HIV-1
      disease were treated with a combination of efavirenz and Combivir
      (GlaxoSmithKline, Uxbridge, Middlesex, UK). They were evaluated for immune and
      lymphocyte function by standard immunological assays. RESULTS: The median time to
      an undetectable HIV-1 viral load was 12 weeks (range 4-36 weeks). CD4 and CD16/56
      counts increased during treatment and CD8 counts decreased minimally. The main
      side-effects observed were transient sleep disturbances (five patients). In
      addition, we observed a decrease in lymphocyte activation as assessed by CD38
      surface expression. CONCLUSIONS: This study demonstrates that primary HIV-1
      infection can be treated with NNRTI-based HAART.

PMID- 14731167
TI  - The onset of HIV infection in the Leningrad region of Russia: a focus on drug and
      alcohol dependence.
AB  - OBJECTIVES: Within 5 years, 5 million Russians may be infected with HIV.
      Currently, injection drug use is the major risk factor for HIV. As Russia's
      alcohol consumption per capita is among the highest in the world, alcohol
      associated behaviours may be an important contributor to the HIV epidemic. Our
      objective was to examine the prevalence of HIV infection among drug- and alcohol
      dependent patients in a regional narcology hospital and in the general population
      in Leningrad. METHODS: All patients in the Narcology Hospital, Leningrad Regional
      Center of Addictions (LRCA), were tested for HIV antibody between 1997 and 2001.
      We reviewed these clinical records (i.e. serostatus, gender, age, and addiction)
      and data from the HIV/AIDS Center in the Leningrad Region (1997-2001). RESULTS:
      From 1997 to 2001, HIV prevalence at the LRCA increased from 0 to 12.7% overall,
      33.4% among drug-dependent patients and 1.2% among alcohol-dependent patients.
      During the same 5-year period (1997-2001), 2826 persons were registered at the
      HIV/AIDS Center: 6, 6, 51, 780, and 1983 persons in 1997, 1998, 1999, 2000 and
      2001, respectively. CONCLUSIONS: HIV infection is exploding in the Leningrad
      Region, currently in injection drug users (IDUs) but potentially more broadly.
      The known high per capita alcohol intake in Russia heightens concern regarding
      the sexual transmission of HIV. Interventions to prevent such a development
      should include use, and assessment of the effectiveness, of known HIV prevention
      measures for at-risk and infected individuals.

PMID- 14731168
TI  - Correlates of antiretroviral treatment breaks.
AB  - OBJECTIVE: To identify key relationships between the decision to take a break
      from antiretroviral treatments and potential clinical and social antecedents.
      METHODS: An analysis of a self-completed survey of various clinical and social
      aspects of the lives of people living with HIV/AIDS (PLWHA) distributed
      nationally in Australia was carried out. RESULTS: The questionnaire was completed
      by a sample of 894 PLWHA. From this sample, three groups of interest were
      identified: a 'no break' group that had been using antiretrovirals continuously
      (n=378), a 'lifestyle break' group that had taken a break for purely lifestyle
      reasons on their last occasion (n=76), and a 'clinical break' group that had
      taken a break for purely clinical reasons on their last occasion (n=99). Clinical
      breaks were found to be longer than lifestyle breaks and involved more
      consultation with doctors. Differences were also found between the two break
      types in effects on the respondents' health and well-being. The clinical break
      group was further found to experience a higher level of health difficulties on a
      range of variables, while the lifestyle break group was younger, had a longer
      experience of HIV and its consequences, and engaged in greater participation in
      activities associated with both pleasure and risk. CONCLUSIONS: The analyses
      offer a pattern of health and social factors that places the HIV-positive
      individual, as a social actor, squarely within the experience of treatment
      interruptions. Understanding the social motivations and correlates of treatment
      interruption offers new challenges in maximizing the efficacy of health
      maintenance and support for PLWHA.

PMID- 14731169
TI  - Determinants of long-term highly active antiretroviral treatment efficacy.
AB  - OBJECTIVES: Predictors of the efficacy of highly active antiretroviral therapy
      (HAART) have been investigated in several studies. To increase current knowledge,
      the study aimed to acquire comprehensive data over an extended observation time,
      to obtain information on possible performance differences among individual drugs,
      and to identify factors with influence on the initial response to a HAART regimen
      and the sustainability of the response. METHODS: The data were obtained from a
      prospective, single University Medical School HIV cohort. Clinical, laboratory,
      and treatment parameters for 475 patients were collected over 4.5 years. HAART
      efficacy was determined by analysis of variance and multivariate survival
      analysis. RESULTS: The overall initial complete response (CR) (<500 HIV-1 RNA
      copies/mL) was 76.3%. Use of indinavir [odds ratio (OR)=2.747, P=0.0009] and the
      number of new nucleoside reverse transcriptase inhibitors (NRTIs) (OR=1.862,
      P=0.0017) were positively associated with CR, while initial peripheral blood HIV
      RNA concentration (OR=0.383, P<0.0001), use of saquinavir hard gel capsules
      (OR=0.531, P=0.0302), the number of successive HAART regimens (OR=0.631,
      P<0.0001), and the number of previously used NRTIs (OR=0.728, P=0.0081) were
      negatively associated with CR. Sustainability of CR was positively correlated
      with use of indinavir [hazard ratio of relapse (HR)=0.255, P<0.0001] and
      haemoglobin levels (HR=0.873, P=0.0124), but negatively correlated with initial
      HIV RNA concentration (HR=1.273, P=0.0003) and the number of previously used
      NRTIs (HR=1.587, P<0.0001). A higher number of consecutive HAART regimens was
      associated with a markedly reduced CR, but with only a slightly higher risk of
      relapse. CONCLUSIONS: The initial response to HAART, as well as long-term
      efficacy, depends strongly on a few fundamental parameters that can easily be
      assessed in a clinical setting. There is a need for effective suppression of HIV
      replication over decades, and these factors should be considered early in
      treatment planning to identify patients with an unfavourable profile of risk
      factors for treatment failure.

PMID- 14731170
TI  - Oral candidiasis and seborrheic dermatitis in HIV-infected patients on highly
      active antiretroviral therapy.
AB  - BACKGROUND: Mucocutaneous manifestations such as oral candidiasis (OC) and
      seborrheic dermatitis (SD) are very common HIV-related opportunistic events and
      are usually initial markers of immunodeficiency. AIM: The purpose of this study
      was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in
      the regression of HIV-associated OC and SD. METHODS: In a prospective study, 120
      HIV-infected patients with OC and SD were divided into two groups: HAART-treated
      patients (group 1, n=76) and non-HAART-treated patients (group 2, n=44). Non
      HAART-treated patients were given antimicrobial therapy. Study subjects were
      matched for sex, age, risk, and stage of HIV infection. The results were analysed
      by chi2 test and the Kaplan-Meier method. RESULTS: At baseline, OC was evident in
      59 (77.7%) of the HAART-treated patients and in 34 (77.3%) of the non-HAART
      treated patients, while SD was present in 19 (25.0%) of the HAART-treated
      patients and in 17 (38.6%) of the non-HAART-treated patients. After a median
      follow-up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and
      16 (84.2%) of the HAART-treated patients, respectively. In the control group,
      regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients,
      respectively, during the same period. CONCLUSIONS: HAART showed greater efficacy
      than standard antimicrobial therapy for the treatment of OC and SD in HIV
      infected patients.

PMID- 14731171
TI  - Evaluation of the impact of highly active antiretroviral therapy on immune
      recovery in antiretroviral naive patients.
AB  - OBJECTIVES: To examine the extent of immune reconstitution in treatment-naive
      patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly
      active antiretroviral therapy (HAART). METHODS: Thirteen antiretroviral naive
      patients were evaluated longitudinally for 48 weeks on HAART utilizing immune
      functional and lymphocyte phenotyping assays, including lymphocyte proliferation
      assay, flow cytometric evaluation of cell surface markers, and delayed type
      hypersensitivity skin tests. Virologic responses were monitored using
      commercially available viral load assays and gag/pol mRNA quantification using
      simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization
      (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function
      was evaluated for a subset of four patients using real-time polymerase chain
      reaction (PCR) for T-cell receptor excision circle (TREC) quantification and
      thymic scans using computerized axial tomography (CT) of the thymus. RESULTS:
      HAART initiation resulted in a significant decline in plasma viremia and
      percentage of infected peripheral blood cells, and a rise in CD4 T cells from a
      baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The
      rise was predominately in CD4 memory cells. Naive T cells also increased in
      number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were
      elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and
      36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells
      increased from a baseline median of 169 to 381 cells/microL at week 48. Both
      soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined
      by week 48. HIV p24 lymphocyte proliferation assay responses were transiently
      detected in three patients. TREC values increased from a median 6400
      copies/microg at baseline to a week-48 median value of 26 697 copies/microg.
      CONCLUSION: Immune functional reconstitution was not achieved in these HAART
      naive patients.

PMID- 14731172
TI  - Association between periodontal and peri-implant conditions: a 10-year
      prospective study.
AB  - OBJECTIVES: The aims of this study were to (1) compare prospectively the clinical
      and radiographic changes in periodontal and peri-implant conditions, (2)
      investigate the association of changes in periodontal parameters and peri-implant
      conditions over a mean observation period of 10 years (8-12 years) after implant
      installation, and (3) evaluate patient risk factors known to aggravate the
      periodontal conditions for their potential influence on the peri-implant tissue
      status. MATERIALS AND METHODS: Eighty-nine partially edentulous patients with a
      mean age of 58.9 years (28-88 years) were examined at 1 and 10 years after
      implant placement. The patients contributed with 179 implants that were placed
      after comprehensive periodontal treatment and restored with crowns or fixed
      partial dentures. One hundred and seventy-nine matching control teeth were chosen
      as controls. Also, the remaining teeth (n=1770) in the dentitions were evaluated.
      Data on smoking habits and general health aspects were collected at 1 and 10
      years as well. RESULTS: At 10 years, statistically significant differences
      existed between implants and matching control teeth with regard to most of the
      clinical and radiographic parameters (P<0.01) with the exception of plaque index
      (PII) and recession. Multiple regression analyses were performed to associate
      combinations of periodontal diagnostic parameters to the peri-implant conditions:
      probing attachment level (PAL) at implants at 10 years was associated with
      implant location, full-mouth probing pocket depth (PPD) and full-mouth PAL
      (P=0.0001, r2=0.36). PPD at implants at 10 years correlated to implant location,
      full-mouth PPD and full-mouth PAL (P<0.001, r2=0.47). Marginal bone level at
      implants at 10 years was significantly associated to smoking, general health
      condition, implant location, full-mouth PAL and change over time in full-mouth
      PPD (P<0.001, r2=0.39). CONCLUSIONS: These results present evidence for the
      association between periodontal and peri-implant conditions and the changes in
      these tissues over 10 years in partially edentulous patients.

PMID- 14731173
TI  - Effect of implant design on survival and success rates of titanium oral implants:
      a 10-year prospective cohort study of the ITI Dental Implant System.
AB  - AIM: The aim of this 10-year study (observation time 8-12 years, mean: 10 years)
      was to compare the survival rates, success rates and incidences of biological
      complications using three different implant designs of the ITI Dental Implant
      System. MATERIAL AND METHODS: In 89 dental patients treated comprehensively, a
      total of 112 hollow screw (HS), 49 hollow cylinder (HC) and 18 angulated hollow
      cylinder (AHC) implants were installed depending on the available bone volume and
      according to prosthetic needs. One and 10 years after surgical placement,
      clinical and radiographic parameters were assessed. The incidences of peri
      implantitis according to various thresholds were registered over 10 years of
      maintenance. RESULTS: Success criteria at 10 years were set at: pocket probing
      depth (PPD)< or =5 mm, bleeding on probing (BoP)-, bone loss < 0.2 mm annually.
      The survival rate for HS was 95.4%, for HC 85.7% and for AHC 91.7%. Ninety
      percent of all the HS, 71% of the HC and 88% of the AHC did not present with an
      incidence of peri-implantitis over the 10 years, HC having significantly higher
      incidence of peri-implantitis than HS (P< 0.004). With the success criteria set
      above, a success rate for HS of 74%, for HC of 63% and for AHC of 61% was
      identified at 10 years. However, including a definition of PPD< or =6 mm, BoP -
      and bone loss < 0.2 mm annually for success, the rates for HS were 78%, for HC
      65% and for AHC 67%, respectively. Basing success criteria purely on clinical
      parameters (without radiographic analysis), such as: PPD< or =5 mm and BoP-, the
      success rates increased to 90%, 76% and 89%, respectively. With PPD< or =6 mm and
      BoP - as success criteria chosen, the respective rates were 94%, 82% and 94% for
      HS, HC and AHC implants, respectively. CONCLUSIONS: A significantly higher
      survival rate as well as a significantly lower incidence of peri-implantitis was
      identified for hollow screw design ITI Dental Implants after 10 years of service
      when compared to hollow cylinder design ITI Dental Implants (95.4% vs. 85.7%; 10%
      vs. 29%). Depending on the setting of the threshold criteria for success, success
      rates are highly variable and hence, reporting of success rates with elaboration
      on the criteria set appears crucial for comparison of different studies.

PMID- 14731174
TI  - Histomorphometrical and clinical comparison of submerged and nonsubmerged
      implants subjected to experimental peri-implantitis in dogs.
AB  - OBJECTIVES: Soft and hard tissue healing around submerged and nonsubmerged
      versions of one dental implant design was evaluated in an experimental canine
      peri-implantitis model. MATERIAL AND METHODS: Forty-eight c.p. Ti-implants with
      integrated (one-piece=OPI) or screw-on (two-piece=TPI) abutments were inserted in
      edentulous mandibles of eight beagle dogs, one OPI and one TPI with connected
      abutments for nonsubmerged and one TPI without abutment (SMI) for submerged
      healing. After 3 months, all implants were functionally loaded, and at 4 months
      peri-implantitis was ligature-induced in one jaw side. Intravital
      polyfluorochrome labeling, monthly conventional radiography and gingival probing
      of all 48 implants were performed until sacrifice 8 months postimplantation.
      Undecalcified ground sections in the bucco-lingual and mesio-distal planes of
      four dogs (23 implants, one implant lost) were evaluated by light and
      fluorescence microscopy. The immunohistochemical and SEM-vascular corrosion cast
      results of the four other dogs (24 implants) will be reported elsewhere. Levels
      of alveolar bone-to-implant contact (ABICL), alveolar crest (ACL) and junctional
      epithelium-to-implant contact were determined by computer-assisted histometry.
      Peri-implant alveolar bone loss (=saucerization) was assessed on the radiographs
      and calculated as ACL minus ABICL from histometric data. RESULTS: Around SMIs and
      OPIs without ligature less plaque adhesion and lower gingival indices were found
      when compared to TPIs. Radiologically, all ligatured, but also some nonligatured
      implants showed alveolar bone loss. Histometry demonstrated reduced ABICL around
      all these implants. Saucerization was more pronounced on the lingual and mesio
      distal sides. Particularly around TPIs, bone resorption was still active or bone
      formation was impaired on fluorochrome labeling. Only around SMIs and one OPI
      without ligature continuing alveolar bone formation reflected by gains in ABICL
      were found. CONCLUSION: The clinical and histometric results of this study
      demonstrate that healing of submerged SMIs was not impaired by the two-stage
      procedure, resulting in equally good healing as around nonsubmerged OPIs.
      However, peri-implantitis plaque-induced by ligature and/or dilated abutment
      connection microgaps in TPIs affected alveolar bone-to-implant contacts more than
      transmucosal or submerged healing mechanisms.

PMID- 14731175
TI  - Influence of implant microstructure on the osseointegration of immediate implants
      placed in periodontally infected sites. A histomorphometric study in dogs.
AB  - The aim of this study was to evaluate the influence of implant microstructure on
      the osseointegration of immediate implants placed into infected sites. During 12
      weeks, periodontitis was induced in six dogs in the areas of the first to fourth
      mandibular premolars of both sides. The teeth were extracted and the implants
      were placed immediately. Implant placement was randomly assigned so that for each
      side in the mandible a different implant surface, a new grit-blasted/acid-etched
      group 1 or titanium plasma spray surface group 2 was used, totaling 36 implants
      in the experiment. The animals were killed 12 weeks after implant placement. Two
      histomorphometric analyses were performed: percentage of bone/implant contact
      (BIC) and analyses of the bone density in adjacent and distant areas from the
      implant surface. The results showed that the percentages of BIC were 52.7% and
      42.7% for groups 1 and 2, respectively. The bone density analysis revealed that
      the percentages of bone in the adjacent areas were 66.6% and 58.8%, and in the
      distant areas from the implants were 58.7% and 55.8% for groups 1 and 2,
      respectively. The mean differences of BIC were verified through the Mann-Whitney
      test and differences in bone density through the Kruskal-Wallis test. The
      differences were not statistically significant (P>0.05). In conclusion,
      osseointegration of implants placed into a more challenging healing situation
      such as immediate implants into periodontally compromised sites was successful
      for both surfaces; however, the grit-blasted/acid-etched surface, although not
      statistically significant, had a slightly better performance when compared to the
      titanium plasma spray surface for all the parameters studied.

PMID- 14731176
TI  - Influence of implant microstructure on the dynamics of bone healing around
      immediate implants placed into periodontally infected sites. A confocal laser
      scanning microscopic study.
AB  - This study evaluated by fluorescence analysis the influence of implant
      microstructure on the placement of immediate implants in periodontally infected
      sockets. Periodontal disease was induced during 12 weeks bilaterally from P1 to
      P4 in six dogs. The teeth were extracted and immediate implants were placed. Each
      dog received six implants: three with Friadent experimental surface (grit
      blasted/acid etched - FES group) and three covered with titanium plasma spray
      (TPS group), for a total of 36 Frialit-2 stepped cylinder implants. During the
      healing period, fluorescent bone markers were injected to study the bone
      remodeling around the implants. The dyes were injected in the following sequence:
      oxytetracyclin hydrochloride 3 days and 8 weeks, calcein green 4 weeks after the
      implantation and alizarin red S 3 days before killing. The animals were
      anesthetized and killed 12 weeks after implant placement. The mandibles were
      removed, dissected and processed for analyses of the percentage of newly formed
      bone surrounding the implant using a confocal laser scanning microscope. There
      were no significant statistical differences in bone formation (Mann-Whitney)
      between groups (FES group: 5.28% formation at 3 days, 10.3% at 4 weeks, 21.14% at
      8 weeks and 6.98% at 12 weeks; TPS group: 3.36% at 3 days, 9.58% at 4 weeks,
      14.57% at 8 weeks and 7.08% at 12 weeks). However, covariance analysis showed
      that the percent of marked bone was statistically greater for the FES group when
      compared to the TPS group, between the 3-day and 8-week periods of evaluation.

PMID- 14731177
TI  - Osseointegration of Osseotite and machined titanium implants in autogenous bone
      graft. A histologic and histomorphometric study in dogs.
AB  - It has been shown that a roughened implant surface results in a higher percentage
      of bone to implant contact (%BIC) than a machined one. A modified implant surface
      using a dual thermo-acid etching process (Osseotite) has been introduced and
      evaluated clinically, mechanically and histologically. The aim of the present
      study was the histological evaluation of the %BIC between the Osseotite or
      machined surfaces and the autogenous bone graft. Twenty-two custom-made split
      type 10-mm-long implants having two opposing surfaces (Osseotite and machined)
      were placed between the cranial and caudal dorsal iliac spine at the iliac wing
      of two adult mongrel dogs. An artificial bone defect was created leaving a 2 mm
      empty space around the coronal 5 mm of the implants, while the apical 5 mm was
      stabilized in the existing basal bone. The defects around the implants were
      filled with particulate autogenous bone graft, covered by an Osseoquest membrane,
      and left to heal for 5 months. All inserted implants showed a complete
      integration in the bone tissue. It was found that the resulting %BIC at the
      Osseotite surface was significantly higher than at the machined one in both
      regenerated (46.44+/-15.81% vs. 28.59+/-12.04%) and basal bone areas (32.32+/
      15.09% vs. 17.25+/-7.40%). The findings of this study imply that the use of
      autogenous bone graft resulted in significantly higher %BIC values in the
      regenerated area than in the basal bone area itself, for both implant surfaces.

PMID- 14731178
TI  - Effect of GBR and fixture installation on gingiva and bone levels at adjacent
      teeth.
AB  - Guided bone regeneration (GBR) is frequently used in oral implantology. It is
      unclear to what extent GBR affects the periodontium of adjacent teeth. Therefore,
      the present study quantifies changes in the proximal gingiva and bone levels at
      these teeth in 30 patients. Staged surgery involved a standard GBR treatment,
      randomly using resorbable membranes with a bone substitute or non-resorbable
      membranes with or without a bone substitute, followed by fixture installation at
      6 months and abutment connection a further 6 months later. The data were sampled
      at each surgery and analysed using MANOVA. Twelve months after GBR, there was on
      average a small but statistically significant amount of proximal gingival
      recession (0.75 mm) and bone resorption (0.34 mm) observed, of which 50% was the
      result of GBR surgery. No significant differences were found between the
      different GBR treatment modalities. It is concluded that GBR treatment may have a
      small negative effect on the levels of the free gingival margin and alveolar bone
      at adjacent teeth, which is in most patients not clinically relevant.

PMID- 14731179
TI  - Growth-associated protein-43 immunoreactivity in human oral mucosa in dentate
      subjects, in edentulous patients and after implant-anchored rehabilitation.
AB  - OBJECTIVES: This study investigates expression of the neural growth-associated
      protein 43 (GAP-43) in the oral mucosa of (A) normal dentate subjects, (B)
      edentulous patients rehabilitated with conventional denture and (C) those
      rehabilitated with mandibular implant-retained overdentures (MIR-OVD), in the
      long term. This study evaluates morphological changes in the distribution and
      representation of sensory terminations and corpuscles in the alveolar mucosa
      under the action of different masticatory or prosthetic loads, in the three
      clinical groups. MATERIAL AND METHODS: GAP-43 immunoreactivity (-ir) was compared
      with the distribution of nerves fibres in the mucosa, as visualised using anti
      protein gene product 9.5 (PGP 9.5), a general marker for peripheral nerves and
      terminals. RESULTS: GAP-43-ir was found to be highly expressed in the corium and
      submucosa in specimens from edentulous subjects wearing conventional denture and
      presenting a reduced number of PGP 9.5-ir nerves in the mucosa, but not in
      specimens from control subjects or patients wearing MIR-OVD, which on the
      contrary show a higher number of PGP 9.5-ir mucosal sensory fibres. CONCLUSION:
      As the mucosa under traditional denture has been shown to possess reduced
      innervation and the histological aspect of chronic overloading, these results may
      be considered indicative of a tentative induction to nerve re-growth in the under
      innervated epithelium, or as a response to chronic inflammation. The detection of
      GAP-43-ir suggests that human oral mucosa presents signs of potential nerve
      plasticity also in the elderly, and that the type of rehabilitation and the
      condition of masticatory load transfer to the mucosa have important effects on
      the nerves underneath.

PMID- 14731180
TI  - Vertical alveolar ridge augmentation by means of a titanium mesh and autogenous
      bone grafts.
AB  - The aim of this study is to evaluate a surgical protocol for vertical ridge
      augmentation in the maxilla and mandible using autogenous onlay bone graft
      associated with a titanium mesh. A group of 18 partially edentulous patients,
      presenting the need for vertical bone augmentation of at least 4 mm, were treated
      before implant placement. During the first surgery, an autogenous bone graft was
      harvested from either the mandibular ramus or the mental symphysis and secured by
      means of titanium screws. Particulate bone was added and a titanium micro-mesh
      was used to stabilize and protect the graft. After a mean interval of 4.6 months,
      meshes and screws were removed and 37 endosseous implants were successfully
      placed. The desired bone gain was reached in all patients. Mean vertical bone
      augmentation obtained was 4.8 mm (range 4-7 mm). No major complications were
      recorded at recipient or donor sites. Abutment connection was carried out 2-3
      months after implant placement. No implant was lost. Clinical parameters and
      probing depth, after prosthetic reconstruction, demonstrated the presence of a
      healthy peri-implant mucosa. The preliminary results suggest that, by using the
      presented technique, patients can be successfully rehabilitated by means of
      implant-supported prosthesis 6-7 months after the first surgery, even in case of
      severely atrophied maxilla.

PMID- 14731181
TI  - Alveolar distraction osteogenesis vs. vertical guided bone regeneration for the
      correction of vertically deficient edentulous ridges: a 1-3-year prospective
      study on humans.
AB  - The purpose of this prospective study was to compare vertical guided bone
      regeneration (GBR) and vertical distraction osteogenesis (DO) for their ability
      in correcting vertically deficient alveolar ridges and their ability in
      maintaining over time the vertical bone gain obtained before and after implant
      placement. Eleven patients (group 1) were treated by means of vertical GBR with
      autogenous bone and e-PTFE membranes, while 10 patients (group 2) were treated by
      means of DO. In group 1, six patients received implants at the time of GBR
      (subgroup 1A), while five patients had implants placed at the time of membrane
      removal (subgroup 1B). In group 2, implants were placed at the time of
      distraction device removal. A total of 25 implants were placed in group 1 and 34
      implants were placed in group 2 patients. Three to 5 months after implant
      placement, patients were rehabilitated with implant-borne dental prostheses. The
      following parameters were evaluated: (a) bone resorption of the regenerated
      ridges before and after implant placement; (b) peri-implant clinical parameters
      1, 2, and 3 years after prosthetic loading of implants; (c) survival and success
      rates of implants. Bone resorption values before and after implant placement were
      significantly higher in group 1. The results suggested that both techniques may
      improve the deficit of vertically resorbed edentulous ridges, although
      distraction osteogenesis seems to be more predictable as far as the long-term
      prognosis of vertical bone gain is concerned. Implant survival rates as well as
      peri-implant clinical parameters do not differ significantly between the two
      groups, whereas the success rate of implants placed in group 2 patients was
      higher than that obtained in group 1 patients.

PMID- 14731182
TI  - Histologic findings at augmented bone areas supplied with two different bone
      substitute materials combined with sinus floor lifting. Report of one case.
AB  - This case report is focused on the histologic findings of bone tissue supplied
      with two different hydroxyapatites (HAs) used for maxillary sinus floor grafting
      in the same patient after various healing intervals. An insufficient unilateral
      sinus floor grafting with Bio-Oss biomaterial was followed by an additional
      grafting procedure with Algipore biomaterial performed 4 years later. Bone
      samples obtained during second-stage dental implantation contained the
      interesting combination of Bio-Oss, a bovine anorganic bone substitute, and
      Algipore, a porous algae-derived HA, in close vicinity, yet after different
      healing periods. Light microscopy exhibited satisfactory osseointegration of both
      grafting materials. However, Bio-Oss biomaterial showed no evidence of
      substantial remodeling after a healing period of 4.5 years. On the other hand,
      Algipore particles demonstrated signs of remodeling by being locally resorbed and
      partially replaced with newly formed bone already within 6 months.

PMID- 14731183
TI  - Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel
      matrix proteins on the healing of critical-size defects.
AB  - OBJECTIVES: To evaluate the effect of guided bone regeneration (GBR) in
      combination with or without deproteinized bovine bone mineral (DBBM) and/or an
      enamel matrix derivative (EMD) on the healing of critical-size calvarial defects.
      MATERIAL AND METHODS: Forty rats were used. In all animals, a standardized
      critical-size calvarial defect was created surgically. The animals were randomly
      allocated into 4 groups of 10 animals each. Group A: One calvarial defect was
      left untreated, while the galeal and the cerebral aspect of the contralateral
      defect were covered with a bioresorbable membrane (GBR). Group B: One calvarial
      defect was filled with EMD, while the contralateral defect was treated with GBR
      and EMD. Group C: One defect was filled with DBBM, while the contralateral defect
      was treated with combination of GBR and DBBM. Group D: One defect was filled with
      DBBM combined with EMD, while the contralateral defect was treated with
      combination of GBR, DBBM and EMD. The healing period was 4 months. Five specimens
      from each group were macerated and the length, the width and the vertical
      dimension (thickness) of the remaining defect were evaluated by a
      stereomicroscope. The remaining specimens in each group were analyzed
      histologically. RESULTS: The defects of the macerated specimens that were left
      untreated or were treated only by EMD, DBBM and combination of EMD and DBBM did
      not present predictably complete healing of the defects. All the defects where
      GBR was applied alone or combined with DBBM and/or EMD presented always complete
      healing (P<0.05). The combined use of GBR with EMD and/or DBBM did not offer any
      significant advantage above GBR alone in terms of healing of the length and the
      width of the defect. However, the vertical dimension of the defect was
      significantly higher (P<0.05) in the GBR-treated specimens of Groups C and D. The
      histological analysis supported these findings. CONCLUSION: The predictability of
      bone formation in critical-size defects depends mainly on the presence or absence
      of barrier membranes (GBR). The combined use with deproteinized bovine bone
      mineral and/or enamel matrix proteins did not significantly enhance the potential
      for complete healing provided by the GBR procedure.

PMID- 14731184
TI  - Use of a mineralized collagen membrane to enhance repair of calvarial defects in
      rats.
AB  - The aim of the present study was to evaluate mineralized collagen membranes for
      enhancement of bone regeneration in calvarial defects. Forty adult female Sprague
      Dawley rats received calvarial full thickness defects with a diameter of 8 mm. In
      20 animals, the defects were covered with a mineralized collagen membrane, and 20
      animals served as controls. After 6, 13, 26 and 52 weeks, bone regeneration was
      evaluated using undecalcified thick-section histometry. There was no clear
      enhancement of bone regeneration during the first 26 weeks after the operation.
      Bone regeneration underneath the membrane produced consistently thicker bone,
      albeit without statistical significance. Accumulation of membrane material
      occurred in the center of the defects surrounded by multinuclear giant cells
      during early stages of healing. After complete resorption of the membrane,
      significantly increased bone formation was seen after 52 weeks in the defects
      that had received membrane coverage. It was concluded that mineralization in the
      present form did not increase mechanical strength of the membrane to prevent
      interference of the membrane with bone regeneration in the defect. The reason for
      the increase in bone formation after resorption of the membrane after 26 weeks
      remains to be clarified.

PMID- 14731185
TI  - Effects of tricalcium phosphate bone graft materials on primary cultures of
      osteoblast cells in vitro.
AB  - The aim of this study was to evaluate beta-tricalcium phosphate (beta-TCP
      Cerasorb Curasan-Germany) graft materials on specific parameters of rat
      osteoblast activity in vitro. Primary culture osteoblastic cells were isolated
      from neonatal rat calvaria by sequential collagenase digestion. To analyze the
      effect of biomaterials on cell proliferation, cell numbers and viability of the
      cells were cultured on the graft material for 24, 48 or 96 h. Osteoblast cells
      cultured in DMEF-12 media supplemented with 10% fetal calf serum were used as the
      control group. [3H]thymidine was added during the last 2 h of the incubation. The
      cell numbers of each well were counted. Cell viability was estimated by counting
      the number of cells, which excluded trypan blue solution. Scanning electron
      microscopy was used to observe for visualizing the interactions between
      osteoblastic cells and TCP graft material. The proportion of cells undergoing DNA
      synthesis, estimated by thymidine uptake, was significantly (P<0.05) greater on
      the control group after the 24- and 48-h incubations. Regarding the cell numbers
      the difference was not statistically significant for the three time points. The
      number of viable cells recovered was similar for the two groups. No morphological
      differences were observed in cell morphology on TCP graft material and the
      control group. The results demonstrate that TCP graft material has no adverse
      effect on cell count, viability and morphology, and this material provides a
      matrix that favors limited cell proliferation.

PMID- 14731186
TI  - Grafting of deproteinized bone particles inhibits bone resorption after maxillary
      sinus floor elevation.
AB  - OBJECTIVES: To evaluate the value of deproteinized bone particles on bone
      resorption in the augmented space after maxillary sinus floor elevation in
      rabbits. MATERIAL AND METHODS: A total of 20 rabbits underwent bilateral
      grafting, using blood clots (control group) and deproteinized bone particles
      (experimental group), and followed with histologic and histomorphometric
      analysis. RESULTS: Two weeks after grafting, the augmented space was almost
      completely obliterated by both newly formed bone and fibrous connective tissue in
      the control group. Some osteoclasts were found on the surface of newly formed
      bone, especially near the elevated sinus membrane. In the experimental group,
      newly formed bone was found along the elevated sinus membrane, the cortical wall
      of the augmented space, and the surface of deproteinized bone particles near the
      cortical wall. Some osteoclasts were found along the deproteinized bone particles
      and a few adhered to the surface of the newly formed bone. Eight to 10 weeks
      after implantation in the control group, most of the newly formed bone had been
      resorbed. In the experimental group, newly formed bone was found in most parts of
      the convex augmented space. Histomorphometrical analysis showed that the
      augmented height was significantly higher in the experimental group than in the
      control group at all evaluation times. Bone area was significantly higher in the
      experimental group than in the control group at 6, 8, and 10 weeks after
      implantation. The area of grafted deproteinized bone particles did not change
      significantly from 2 to 10 weeks. CONCLUSION: Slowly resorbed deproteinized bone
      particles contribute to stable augmentation of the maxillary sinus floor by
      inhibiting bone resorption.

PMID- 14731188
TI  - A pioneer of neuropsychiatry: Professor Alwyn Lishman. Interview by Michael
      Salzberg.

PMID- 14731189
TI  - The policy and ethical implications of genetic research on attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: To review the policy and ethical implications of recent research on
      the molecular genetics of attention deficit hyperactivity disorder (ADHD).
      METHOD: MEDLINE and psycINFO database searches were used to identify studies on
      the genetics of ADHD. The implications of replicated candidate genes are
      discussed. RESULTS: The findings for most genes have been inconsistent but
      several studies have implicated the genes in the dopaminergic pathway in the
      aetiology of ADHD. CONCLUSIONS: The current evidence on the genetics of ADHD is
      insufficient to justify genetic screening tests but it will provide important
      clues as to the aetiology of ADHD. Genetic information on susceptibility to ADHD
      has the potential to be abused and to stigmatize individuals. Researchers and
      clinicians need to be mindful of these issues in interpreting and disseminating
      the results of genetic studies of ADHD.

PMID- 14731190
TI  - A consideration of the relationship between the Rules of Court and the Code of
      Ethics in forensic psychiatry.
AB  - OBJECTIVE: To consider the relationship between the Rules of Court for expert
      witnesses and the revised Ethical Guideline No. 9 and Practice Guideline No. 9 of
      the Royal Australian and New Zealand College of Psychiatrists (RANZCP) and how
      this affects the responsibilities that psychiatrists have to a court and to their
      profession, when they enter the legal arena. METHOD: Literature relevant to the
      subject, the Federal Court rules relating to expert witnesses and the RANZCP
      Guidelines are discussed and compared, with examples used to illustrate
      particular issues that arise from time to time in the civil jurisdiction. A
      distinction is drawn between the functions of those psychiatrists who undertake
      forensic assessment and those who undertake clinical work, and some of the
      ethical challenges facing forensic psychiatrists are considered. RESULTS: The
      Rules of Court relating to expert witnesses and the RANZCP Guidelines No. 9 have
      a complementary relationship and are thus ethically consistent with each other
      and provide a basis for psychiatrists to maintain and enhance the integrity of
      their profession. CONCLUSION: Forensic psychiatry is a particularly complex
      medical speciality and one that can create enormous personal conflict for
      clinicians, especially those who are not forensic consultants. It may therefore
      be time for the College to develop an accreditation process for those prepared to
      undertake further study in the nature and practice of forensic psychiatry.

PMID- 14731191
TI  - Seclusion use with children and adolescents: an Australian experience.
AB  - OBJECTIVE: To summarize the current state of knowledge on the use of seclusion
      and restraint with children and adolescents and to report the findings of an
      exploratory study to identify factors that place a child or adolescent at
      increased risk of seclusion during their admission. METHOD: Literature searches
      were undertaken on MEDLINE, CINAHL and PsycINFO databases. Articles were
      identified that focused specifically on seclusion and restraint use with children
      and adolescents or contained material significant to this population. The study
      reports findings from a retrospective review of patient charts, seclusion
      registers and staffing from an Australian acute inpatient facility. RESULTS: The
      data available in regard to seclusion use in this population is limited and
      flawed. Further research is needed on the use and outcomes of seclusion and
      restraint and on alternative measures in the containment of dangerousness. Both
      the literature and this study find that patients with certain factors are at
      increased risk of being secluded during an inpatient stay. These factors include
      being male, diagnoses of disruptive behaviour disorder and a previous history of
      physical abuse. Staffing factors did not show a relationship to the use of
      seclusion. CONCLUSIONS: There are patient factors that predict increased risk of
      seclusion; these factors and their interrelationships require further
      elucidation. Further research is also needed on the outcomes, both positive and
      negative, of seclusion use and of alternatives to seclusion.

PMID- 14731192
TI  - Sexual abuse, antisocial behaviour and substance use: gender differences in young
      community adolescents.
AB  - OBJECTIVE: To investigate gender-specific relationships between self-reported
      sexual abuse, antisocial behaviour and substance use in a large community sample
      of adolescents. METHOD: A cross-sectional study of students aged, on average, 13
      (n = 2596), 14 (n = 2475) and 15 years (n = 2290), from 27 schools in South
      Australia with a questionnaire including sexual abuse, frequency and severity of
      substance use, depressive symptomatology (CES-D), family functioning (McMaster
      Family Assessment Device), and antisocial behaviour (an adapted 22-item Self
      Report Delinquency Scale). Logistic regression analyses using HLM V5.05 with a
      population-average model were conducted. RESULTS: In the model considered,
      reported sexual abuse is significantly independently associated with antisocial
      behaviour, controlling for confounding factors of depressive symptomatology and
      family dysfunction, with increased risks of three- to eightfold for sexually
      abused boys, and two- to threefold for sexually abused girls, compared to
      nonabused. Increased risks of extreme substance use in sexually abused girls (age
      13) and boys (ages 13-15) are more than fourfold, compared to nonabused. Age
      differences were not statistically significant. CONCLUSION: Childhood sexual
      abuse is a risk factor for the development of antisocial behaviour and substance
      use in young adolescents. Clinicians should be aware of gender differences.

PMID- 14731193
TI  - Cannabis abuse is not a risk factor for treatment outcome in methadone
      maintenance treatment: a 1-year prospective study in an Israeli clinic.
AB  - OBJECTIVE: We addressed the following questions. What are the current and
      lifetime prevalence of cannabis abuse in an Israeli methadone maintenance
      treatment (MMT) clinic? Does cannabis abuse change over time during MMT? Is
      cannabis abuse related to treatment outcome measures such as retention rate and
      the abuse of drugs? Is the abuse of cannabis related to psychopathology, HIV/HCV
      risk-taking and infectious diseases? Do cannabis abusers (CAs) have a different
      psychosocial and demographic profile than nonabusers (NCAs)? Is cannabis abuse
      part of a polydrug abuse tendency or a distinct substance of abuse? METHOD:
      Overlapping samples of either the entire clinic population (n = 283) or all the
      patients who had completed 1 year of MMT treatment (n = 196 of which 20 were re
      entering) underwent random and twice-weekly observed urine analysis for various
      drugs of abuse, responded to self-report questionnaires (SCL-90-R; HIV/HCV risk
      taking behaviours; n = 164), interviews (ASI, n = 176; SCID, n = 151) and
      hepatitis C and HIV testing (n = 149). RESULTS: Lifetime abuse prevalence was
      found in 75% and current abuse at MMT intake in 25%. Abuse did not increase
      significantly over a 1-year period. Cannabis abusers were found to be more often
      polydrug abusers than NCAs. Cannabis abusers did not suffer from more
      psychological distress, infectious diseases, and did not engage in more HCV/HIV
      risk-taking behaviour, nor did they leave treatment earlier than NCAs.
      CONCLUSIONS: Cannabis abuse MMT patients should be treated as polydrug abusers,
      although no specific influences of cannabis abuse on psychological and medical
      conditions of MMT patients have been observed. Treatment policy should take these
      results into consideration.

PMID- 14731194
TI  - Assessing markers of working memory function in dissociative identity disorder
      using neutral stimuli: a comparison with clinical and general population samples.
AB  - OBJECTIVES: Memory functioning is a central conceptual and phenomenological
      aspect of dissociative identity disorder (DID). Most empirical work on memory
      functions in DID has focused on retrieval deficits either within or between
      dissociated identities. The current study attempted to remedy the scant attention
      given to working memory functioning. METHOD: In samples representing the DID, non
      clinical, depressed, posttraumatic stress disorder (PTSD) and psychosis
      populations (n = 10 per group), neutral stimuli were used to examine three
      markers of working memory functioning: one measuring inhibition; one assessing
      facilitation; and one measuring interference. RESULTS: With the exception of the
      psychosis sample all groups displayed significant negative priming in the
      distractor inhibition condition. Facilitation effects were demonstrated by the
      DID and PTSD groups only. Interference effects were evident in all samples,
      though the DID and non-clinical groups demonstrated significantly more
      interference than the psychosis cohort. Distractor inhibition was related to
      overall schizotypy scores, and dissociation was related to scores in the
      facilitation condition. CONCLUSIONS: The DID sample displayed a completely
      distinct functional working memory profile to the psychosis sample when assessed
      with emotionally neutral stimuli. However, the working memory profile in the DID
      sample was not entirely dissimilar to the other comparison groups.

PMID- 14731195
TI  - The First-Time Fathers Study: a prospective study of the mental health and
      wellbeing of men during the transition to parenthood.
AB  - OBJECTIVE: In comparison to its female counterpart, the transition of men to
      parenthood has been relatively neglected in previous research. The present paper
      argues that men may have gender-specific risk factors for perinatal psychological
      distress and may manifest distress in ways different from women. The prime
      objective of this research was to document changes in psychological, relationship
      and lifestyle parameters in a cohort of first time fathers from pregnancy to the
      end of the first postnatal year. The present paper reports on these changes.
      METHOD: Three hundred and twelve men were assessed at 23 weeks of pregnancy and
      followed up at 3, 6 and 12 months postnatally, using a battery of self-report
      questionnaires covering psychological symptom levels, lifestyle variables and
      relationship/sexual functioning. Two hundred and four men completed all four
      assessments. RESULTS: The men exhibited highest symptom levels in pregnancy with
      general, through small, improvement at 3 months and little change thereafter.
      Lifestyle variables showed small changes over the first postnatal year. Sexual
      functioning appeared to deteriorate markedly from pre-pregnancy levels with only
      minimal recovery by the end of the first year. The results highlight that the
      majority of men anticipated return of sexual activity to pre-pregnancy levels;
      however, this failed to eventuate. CONCLUSIONS: Pregnancy, rather than the
      postnatal period, would appear to be the most stressful period for men undergoing
      the transition to parenthood. The results suggest that the most important changes
      occur relatively early in pregnancy. Thereafter, lack of change (rather than
      change) is the most noteworthy feature. These men appeared to be ill-prepared for
      the impact of parenthood on their lives, especially in terms of the sexual
      relationship. Further research to determine the timing and trigger of stress in
      pregnancy is recommended.

PMID- 14731196
TI  - Suicide after discharge from psychiatric inpatient care: a case-control study in
      Hong Kong.
AB  - OBJECTIVE: To identify the risk period and the risk factors for suicide in
      Chinese psychiatric patients after discharge from inpatient psychiatric
      treatment. The nature of psychiatric aftercare provided to these patients was
      also explored. METHOD: A case control study with 73 patients who were discharged
      from a large psychiatric unit in Hong Kong between January 1996 and December 1999
      and had received coroners' verdict of suicide or undetermined death within the
      same period. Controls were 73 surviving patients discharged from the same unit.
      They were individually matched for sex, age, psychiatric diagnosis, and date of
      discharge. RESULTS: Post-discharge clustering of suicides was observed among the
      cases. Nearly 80% of them died within 1 year of discharge. The most common
      principal diagnosis among the cases was schizophrenia and related psychotic
      disorders. Multivariate analysis showed that suicide was associated with:
      unemployment (OR = 12.2, 95% CI = 2.1 - 70.4), past suicidal attempts (OR = 3.4,
      95% CI = 1.2 - 9.6), maternal mental illness (OR = 13.4, 95% CI = 1.0 - 170.0),
      and suicidal ideation or attempt before the last admission (OR = 5.0, 95% CI =
      1.4 - 18.0). The psychiatric aftercare received by cases and controls were
      generally similar. However, cases were more likely to have had contact with
      health care services in the last week before death (OR = 4.0, 95% CI = 1.3 -
      11.9). CONCLUSIONS: Suicidal risk is high in Chinese psychiatric patients soon
      after discharge. They share some common risk factors for suicide identified in
      Western studies but several differences are evident: the predominance of
      schizophrenia in the suicides; the lower prevalence of substance abuse and
      comorbidity; the low proportion of patients living alone; and the increased
      clinical contact before death but the less suicidal intent expressed in Chinese
      patients. It is necessary to consider these socio-cultural factors in assessment
      of suicidal risk and implementation of suicide prevention strategies in Chinese
      psychiatric patients.

PMID- 14731197
TI  - Genetic screening for susceptibility to depression: can we and should we?
AB  - OBJECTIVE: To summarize current knowledge about genetic susceptibility to mood
      disorders and examine ethical and policy issues that will need to be addressed if
      robustly replicated susceptibility alleles lead to proposals to screen and
      intervene with persons at increased genetic risk of developing mood disorders.
      METHOD: Empirical studies and reviews of the genetics of unipolar and bipolar
      depression were collected via MEDLINE and psycINFO database searches. RESULTS: A
      number of candidate genes for depression have been identified, each of which
      increases the risk of mood disorders two- or threefold. None of the associations
      between these alleles and mood disorders have been consistently reported to date.
      CONCLUSIONS: Screening the population for genetic susceptibility to mood
      disorders is unlikely to be a practically useful policy (given plausible
      assumptions). Until there are effective treatments for persons at increased risk,
      screening is arguably unethical. Screening within affected families to advise on
      risks of developing depression would entail screening children and adolescents,
      raising potentially serious ethical issues of consent and stigmatization. Genetic
      research on depression should continue under appropriate ethical guidelines that
      protect the interests of research participants.

PMID- 14731198
TI  - Paradoxical association between smoking and olfactory identification in psychosis
      versus controls.
AB  - OBJECTIVE: Deficits in olfactory identification have been demonstrated in
      patients with schizophrenia. This study examined the interaction between smoking
      and olfactory identification in patients with psychotic disorders versus well
      controls. METHOD: Olfactory identification was assessed in three groups of
      subjects using the University of Pennsylvania Smell Identification Test (UPSIT).
      Sixteen patients with affective psychoses, 22 patients with nonaffective
      psychoses, and 21 well controls were tested. RESULTS: There was a significant
      interaction between diagnostic classification (patient or control) and smoking.
      Patients who were smokers scored higher on the UPSIT than non-smokers, while
      controls who were smokers scored lower than non-smokers. CONCLUSIONS: Smoking may
      have a 'normalising' effect on olfactory identification in some patients with
      psychosis. Further studies are needed to examine the relationship between
      psychosis, olfactory identification and the effects of nicotine.

PMID- 14731199
TI  - Post-traumatic stress disorder: the importance of recognition.

PMID- 14731200
TI  - Philosophical dimensions for psychiatry.

PMID- 14731201
TI  - Philosophical dimensions for psychiatry.

PMID- 14731202
TI  - Philosophical dimensions for psychiatry.

PMID- 14731209
TI  - A renaissance in electrocardiography.

PMID- 14731210
TI  - Beat-to-beat QT dynamics in healthy subjects.
AB  - BACKGROUND: Measures of QT dynamics express repolarization abnormalities that
      carry prognostic information, but the reproducibility of beat-to-beat QT dynamics
      has never been established. The QT interval is prolonged at night, but how the
      circadian rhythm and heart rate influence the dynamic QT measurements is still
      unsettled. The aims of the present study were: (1) to describe the
      reproducibility of beat-to-beat QT dynamics with respect to intrasubject, between
      subject, and between-observer variability and (2) to describe the normal range,
      circadian variation, and heart rate dependence of QT dynamics. METHODS:
      Ambulatory Holter recordings were performed three times on 20 healthy volunteers
      and were analyzed by two experienced cardiologists. Slope and intercept of the
      QT/RR regression, the variability of QT and R-R intervals expressed as the
      standard deviation, and the relation between QT and RR variability expressed as a
      variability ratio were measured among other QT dynamics. RESULTS: The
      reproducibility of all QT dynamics was good. All QT dynamics showed circadian
      variation when calculated on an hourly basis. The day/night variation in slope
      could be explained by the differences in heart rate, whereas the day/night
      variation in intercept was heart rate independent. CONCLUSION: The present study
      shows that reliable automatic QT measurements could be performed, encouraging
      further evaluation of the clinical value of QT dynamics in risk stratification of
      cardiac patients.

PMID- 14731211
TI  - Utility of a simplified lidocaine and potassium infusion in diagnosing long QT
      syndrome among patients with borderline QTc interval prolongation.
AB  - BACKGROUND: Congenital long QT syndrome (LQTS) is caused by mutations in the
      cardiac Na+ or K+ channels that result in a prolonged QTc interval and increased
      QT dispersion. Na+ channel blockers and K+ can reverse the repolarization
      abnormalities in the Na+ channel variant (LQT3) and K+ channel variant (LQT1,
      LQT2), respectively. The phenotype of LQTS can be difficult to recognize,
      especially when the QTc interval is mildly prolonged. Additional noninvasive
      testing methods are needed to enhance the diagnosis of LQTS. This study compared
      the response of the QTc interval and QT dispersion to a sequential lidocaine/K+
      infusion in LQTS patients with borderline QTc interval prolongation and control
      patients as a means of diagnosing LQTS. METHODS: In this study, eight LQTS
      patients with borderline QTc, defined as QTc < 470 ms, and 10 healthy controls
      received sequential lidocaine/K+ infusion. RESULTS: At baseline, LQTS patients
      had a longer QTc (446 +/- 29 vs 416 +/- 28 ms, P < 0.05) but similar QT
      dispersion (43 +/- 14 vs 29 +/- 10 ms) compared to controls. After lidocaine
      administration, baseline QTc and QT dispersion did not change in either LQTS or
      controls. One LQTS patient had a 54 ms (12%) reduction in his QTc but no change
      in QT dispersion. Following K+ infusion, baseline QTc and QT dispersion decreased
      by 9% (P < 0.005) and 45% (P < 0.005), respectively in LQTS. No effect was seen
      in control patients, where QTc and QT dispersion shortened by 1% (5 +/- 14 ms)
      and 20% (6 +/- 7 ms), respectively, compared to baseline. The combined
      lidocaine/K+ infusion had a sensitivity, specificity, and accuracy of 88%, 100%,
      and 94%, respectively, in diagnosing LQTS. CONCLUSIONS: A simplified sequential
      lidocaine/K+ challenge is accurate in diagnosing LQTS among patients with
      borderline QTc prolongation.

PMID- 14731212
TI  - Structural, functional and autonomic changes in the cardiovascular system in
      growth hormone deficient patients.
AB  - BACKGROUND: Growth hormone deficiency (GHD) is known to cause higher rates of
      cardiovascular mortality. The purpose of the study was to analyze the structural
      and functional changes in the heart and investigate their relation to autonomic
      function as assessed with heart rate variability (HRV). METHODS: Eleven untreated
      GHD patients (mean age 50.4 +/- 10.7 years, M/F: 3/8) and 15 age- and sex-matched
      healthy persons (mean age 45.3 +/- 10.4 years, M/F: 5/10) were compared. Both
      groups were examined with echocardiography, HRV, and exercise testing and
      findings were analyzed. RESULTS: The groups were similar in height, weight, body
      mass index, body surface area, systolic and diastolic blood pressure, heart rate.
      The GHD patients had lower exercise duration and metabolic equivalent (MET)
      compared to controls (7.94 +/- 1.26 vs. 9.8 +/- 1.9 min, P < 0.001, for MET 8.85
      +/- 0.86 vs. 10.7 +/- 2.23, P = 0.03). On echocardiography, GHD patients had
      lower interventricular septum diastolic diameter (9 +/- 0.89 vs. 10.7 +/- 0.88
      mm, P < 0.001) and posterior wall thickness (8.4 +/- 0.93 vs. 9.8 +/- 0.91 mm, P
      = 0.002), and lower left ventricle mass index (90.9 +/- 20 vs. 112 +/- 8 g/m2, P
      = 0.01). Left ventricular ejection fraction was lower in the GHD patients (57.4
      +/- 5.12% vs. 65.5 +/- 4.1%, P < 0.001). Time and frequency domain heart rate
      variability parameters, SDNN, SDANN, VLF, LF ve LF/HF were lower in GHD patients
      compared to controls. There was a significant correlation between left ventricle
      diastolic diameter and LF (r = 0.62, P = 0.02). CONCLUSION: GHD seemed to cause
      decreased left ventricle mass and decreases in the sympathetic components of HRV
      that may have a bearing on the increased cardiovascular risk seen in these
      patients.

PMID- 14731213
TI  - The relationship between plasma endothelin-1, nitric oxide levels, and heart rate
      variability in patients with coronary slow flow.
AB  - BACKGROUND: Coronary slow flow (CSF) is characterized by delayed opacification of
      coronary arteries in the absence of epicardial occlusive disease. In this study,
      we aimed to determine endothelin-1 (ET-1), nitric oxide (NOx) levels and time
      domain heart rate variability (HRV) parameters in patients with CSF and
      relationship among these parameters. METHODS: Thirty-three patients with CSF
      detected in the coronary angiography (17 females; mean age 55 +/- 7) and 19
      patients with normal coronary flow (10 females; mean age 54 +/- 11) as a control
      group were enrolled in the study. Patients were divided into two groups according
      to exercise testing as if positive (group A, n = 8) or negative (group B, n =
      25). RESULTS: Plasma ET-1 levels were higher in the group A patients (28.7 +/-
      17.4 pg/ml) than that of group B (15.9 +/- 10.6 pg/ml) and control group (6.0 +/-
      5.7 pg/ml); and higher in group B patients than that of control group (P < 0.05).
      Although groups A and B did not differ according to plasma NOx levels (23.4 +/-
      13.5 micromol/L vs. 32.8 +/- 22.7 micromol/L, P > 0.05), NOx levels in group A
      were lower than the control group (23.4 +/- 13.5 micromol/L versus 42.5 +/- 15.9
      micromol/L, P < 0.05). Time domain HRV parameters were decreased in all patient
      groups. This was more prominent in group A. Additionally, HRV parameters were
      negatively correlated with ET-1 and TIMI frame counts. TIMI frame count was also
      significantly correlated with ET-1 and NOx levels (r = 0.61, P < 0.0001, r =
      0.30, P < 0.05). Upon intravascular ultrasonography investigation, the common
      finding was longitudinally extended massive calcification throughout the
      epicardial arteries. Mean intimal thickness was 0.50 +/- 0.13 mm (group A; 0.58
      +/- 0.11 mm, group B 0.47 +/- 0.12 mm, P = 0.029). CONCLUSIONS: The present study
      demonstrated that in patients with CSF, both increased plasma ET-1, decreased
      plasma NOx and diffuse atherosclerosis may cause the decrease in HRV by effecting
      myocardial blood flow.

PMID- 14731214
TI  - Increased P wave dispersion and maximum P wave duration after hemodialysis.
AB  - BACKGROUND: Atrial fibrillation is a frequent arrhythmia in patients undergoing
      hemodialysis. The consequences of hemodialysis on P wave durations and P wave
      dispersion have not been fully understood. The objective of this study was to
      study the effect of dialysis on P wave maximum (Pmax), P wave minimum (Pmin), and
      P wave dispersion (Pd). METHODS: We studied Pmax, Pmin, and Pd in 32 patients (17
      men and 15 women, mean age 54 +/- 18 years) with chronic renal failure undergoing
      hemodialysis. The difference between maximum and minimum P wave duration was
      calculated and defined as P wave dispersion (Pd= Pmax- Pmin). RESULTS: There was
      a significant increase in Pmax at the end of dialysis compared to the beginning
      (98 +/- 13 ms vs. 125 +/- 12 ms, P < 0.001). Pmin did not show any significant
      change (71 +/- 11 ms vs. 73 +/- 10 ms, P = 0.42). Pd was significantly increased
      at the end of dialysis (27 +/- 9 ms vs. 52 +/- 11 ms, P < 0.001). There was a
      negative correlation between serum potassium, magnesium, phosphate, blood urea
      nitrogen, and creatinin at the end of dialysis and Pmax and Pd, respectively (P <
      0.05). A weak positive correlation was found between serum calcium, bicarbonate
      at the end of dialysis and Pmax and Pd (P < 0.05). CONCLUSION: Hemodialysis ends
      with significant increase in P wave maximum duration and P wave dispersion, which
      might be responsible for the increased occurrence of atrial fibrillation in these
      groups of patients.

PMID- 14731215
TI  - Clinical significance of QS complexes in V1 and V2 without other
      electrocardiographic abnormality.
AB  - BACKGROUND: In the absence of other electrocardiographic (ECG) abnormalities, QS
      deflections simultaneously in both of the leads V1-V2 may have multiple possible
      causes. Despite much information in the literature indicating that this is an
      unlikely pattern for pure septal infarction, such an ECG diagnosis is frequently
      given. METHODS: Ninety-nine cases having QS deflections in both leads V1 and V2
      but no other ECG abnormality were compared to 99 other patients with entirely
      normal ECGs, to whom they were matched by age, gender, and the presence or
      absence of septal Q waves. Retrospective analysis of medical records was
      performed to determine the nature of any cardiovascular disease in these two
      groups, and to find a possible explanation for the ECG abnormality. RESULTS:
      Because of its intermittence in subjects with multiple ECGs, QS deflections in
      leads V1-V2 appeared most often to be an artifact of precordial lead placement.
      Prior myocardial infarction, or presence of clinical coronary disease was present
      in only about 20% of the cases. Neither the intermittence of Q wave in V2 on
      repeated ECGs nor the absence of septal Q waves was useful in distinguishing
      between those with and without coronary heart disease. CONCLUSIONS: This ECG
      pattern is a sign of prior myocardial infarction in only a minority of cases, and
      in the latter, infarction limited to the interventricular septum is exceptional.
      This ECG finding should be interpreted as a nonspecific QRS abnormality with
      multiple possible causes. Clinical correlation and repeat tracings with attention
      to lead placement will help to clarify its significance.

PMID- 14731216
TI  - Electrocardiographic identification of drug-induced QT prolongation: assessment
      by different recording and measurement methods.
AB  - BACKGROUND: Careful assessment of QT interval prolongation is required before
      novel drugs are approved by regulatory authorities. The choice of the most
      appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval
      measurement in clinical trials requires better understanding of the differences
      among currently available approaches. This study compared standard and Holter
      derived 12-lead ECGs for utility in detecting sotalol-induced QT/QTc and RR
      changes. Manual methods (digitizing pad and digital on-screen calipers) were
      compared for precision of QT and RR interval measurement. METHODS AND RESULTS:
      Sixteen hundred pairs of serial 12-lead digital ECGs were recorded simultaneously
      by standard resting ECG device and by continuous 12-lead digital Holter over 3
      days in 39 healthy male and female volunteers. No therapy was given on the 1st
      day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day,
      respectively. Holter-derived and standard ECGs produced nearly identical sotalol
      induced QT/QTc and RR changes from baseline, as did the manual digipad and on
      screen caliper measurements. The variability of on-screen QT measurement in this
      study was greater than that of digipad. CONCLUSIONS: Digital 12-lead Holter and
      standard 12-lead ECG recorders, as well as the manual digitizing pad and digital
      on-screen calipers, are of equal utility for the assessment of drug-induced
      change from baseline in QT and RR interval, although the variability of the on
      screen method in this study was greater than of the digipad.

PMID- 14731217
TI  - Noninvasive assessment of the biventricular pacing system.

PMID- 14731218
TI  - Evolving myocardial infarction with ST elevation: anatomic considerations
      regarding the correlation between the site of occlusion and injured segments of
      the heart.

PMID- 14731219
TI  - Introductory note to a classic article by Dr. Fred M. Smith.

PMID- 14731220
TI  - The ligation of coronary arteries with electrocardiographic study. 1918.
AB  - This article is based on a study of sixty-six dogs in which known myocardial
      lesions had been produced by the ligation of definite branches of the coronary
      arteries of the heart. While the experiments were made with the primary object of
      determining the change in the electrocardiograms brought about by these
      ligations, other results, anatomic and pathologic, are deemed worthy of brief
      mention.

PMID- 14731221
TI  - QT interval prolongation with global T-wave inversion: a novel ECG finding in
      acute pulmonary embolism.
AB  - OBJECTIVE: The purpose of this study was to report a novel electrocardiographic
      (ECG) phenomenon in acute pulmonary embolism characterized by QT interval
      prolongation with global T-wave inversion. METHODS: Among a total of 140 study
      patients with a confirmed diagnosis of acute pulmonary embolism, patients who
      fulfilled the inclusion criteria for QT interval prolongation with global T-wave
      inversion were examined. Each of these patients had undergone a detailed clinical
      evaluation including testing for myocardial injury and echocardiography. RESULTS:
      QT interval prolongation with global T-wave inversion was found in five patients
      (age 51-68 years) with acute pulmonary embolism. Four were women. Acute pulmonary
      embolism was diagnosed by ventilation-perfusion scan in three patients and by
      spiral computed tomography in other two patients. None of the patients had any
      right or left ventricular regional wall motion abnormalities on echocardiography.
      All patients had changes characteristic of hemodynamically significant pulmonary
      embolism, including right ventricular stunning or hypokinesis and dilatation in
      five patients with paradoxical septal motion in four. Acute coronary syndrome was
      ruled out in each patient by clinical evaluation, serial ECGs and cardiac
      markers, and lack of regional wall motion abnormalities on echocardiography.
      Prolongation of QT intervals (QTc 456-521 ms) with global T-wave inversion was
      noted on presentation. The ECG changes gradually resolved in 1 week in all
      patients with appropriate treatment of acute pulmonary embolism. One patient
      died. None of the patients developed torsade de pointes. CONCLUSIONS: Acute
      pulmonary embolism may occasionally result in reversible QT interval prolongation
      with deep T-wave inversion, and, thus should be considered among the acquired
      causes of the long QT syndrome.

PMID- 14731222
TI  - Identification of quantitative trait loci for growth and carcass composition in
      cattle.
AB  - A genomic screening to detect quantitative trait loci (QTL) affecting growth,
      carcass composition and meat quality traits was pursued. Two hundred nineteen
      microsatellite markers were genotyped on 176 of 620 (28%) progeny from a Brahman
      x Angus sire mated to mostly MARC III dams. Selective genotyping, based on retail
      product yield (%) and fat yield (%), was used to select individuals to be
      genotyped. Traits included in the study were birth weight (kg), hot carcass
      weight (kg), retail product yield, fat yield, marbling score (400 = slight00 and
      500 = small00), USDA yield grade, and estimated kidney, heart and pelvic fat (%).
      The QTL were classified as significant when the expected number of false
      positives (ENFP) was less than 0.05 (F-statistic greater than 17.3), and
      suggestive when the ENFP was <1 (F-statistic between 10.2 and 17.3). A
      significant QTL (F = 19; ENFP = 0.02) was detected for marbling score at
      centimorgan (cM) 54 on chromosome 2. Suggestive QTL were detected for fat yield
      at 50 cM, for retail product yield at 53 cM, and for USDA yield grade at 63 cM on
      chromosome 1, for marbling score at 56 cM, for retail product yield at 70 cM, and
      for estimated kidney, heart and pelvic fat at 79 cM on chromosome 3, for marbling
      score at 44 cM, for hot carcass weight at 49 cM, and for estimated kidney, heart
      and pelvic fat at 62 cM on chromosome 16, and for fat yield at 35 cM on
      chromosome 17. Two suggestive QTL for birth weight were identified, one at 12 cM
      on chromosome 20 and the other at 56 cM on chromosome 21. An additional
      suggestive QTL was detected for retail product yield, for fat yield, and for USDA
      yield grade at 26 cM on chromosome 26. Results presented here represent the
      initial search for quantitative trait loci in this family. Validation of detected
      QTL in other populations will be necessary.

PMID- 14731223
TI  - Mapping of bovine ovulation rate QTL; an analytical approach for three generation
      pedigrees.
AB  - Interval mapping was conducted for ovulation rate quantitative trait loci (QTL)
      using data from two related families from the United States Department of
      Agriculture, US Meat Animal Research Center twinning cattle herd. Both families
      are extended, three generation pedigrees from which records of sons, daughters
      and granddaughters were analysed. Both a method of analysis and results from that
      analysis are reported herein. Results from one of the two families (839802) were
      previously reported, but reanalysis here including the second, related family
      (839803) and a revised statistical model lessens support for the previously
      reported QTL. Results from interval mapping provided evidence for QTL in regions
      corresponding to those previously suggested for chromosomes 7 (chromosome-wise P
      < 0.05) and 19 (chromosome-wise P < 0.01) in the 839802 family, although
      statistical significance was reduced. In contrast to the previous report,
      evidence for a chromosome 5 QTL in the same family was greatly reduced while
      support for a QTL on chromosome 10 increased (chromosome-wise P < 0.01). Analysis
      of data from the related 839803 family failed to replicate evidence of QTL
      observed on either chromosome 7 or chromosome 19 in the 839802 family.

PMID- 14731224
TI  - Power of exclusion for parentage verification and probability of match for
      identity in American Kennel Club breeds using 17 canine microsatellite markers.
AB  - DNA analysis of microsatellite markers has become a common tool for verifying
      parentage in breed registries and identifying individual animals that are linked
      to a database or owner. Panels of markers have been developed in canines, but
      their utility across and within a wide range of breeds has not been reported. The
      American Kennel Club (AKC) authorized a study to determine the power to exclude
      non-parents and identify individuals using DNA genotypes of 17 microsatellite
      markers in two panels. Cheek swab samples were voluntarily collected at Parent
      Breed Club National Specialty dog shows and 9561 samples representing 108 breeds
      were collected, averaging 88.5 dogs per breed. The primary panel of 10 markers
      exceeded 99% power of exclusion for canine parentage verification of 61% of the
      breeds. In combination with the secondary panel of seven markers, 100% of the
      tested breeds exceeded 99% power of exclusion. The minimum probability match rate
      of the first panel was 3.6 x 10(-5) averaged across breeds, and with the addition
      of the second panel, the probability match rate was 3.2 x 10(-8); thus the
      probability of another random, unrelated dog with the same genotype is very low.
      The results of this analysis indicated that, on average, the primary panel meets
      the AKC's needs for routine parentage testing, but that a combination of 10-15
      genetic markers from the two panels could yield a universal canine panel with
      enhanced processing efficiency, reliability and informativeness.

PMID- 14731225
TI  - Diversity and locus specificity of chicken MHC B class I sequences.
AB  - The major histocompatibility complex B (MHC B) region in a standard haplotype of
      Leghorn chickens contains two closely linked class I loci, B-FI and B-FIV. Few
      sequences of B-FI alleles are available, and therefore alleles of the two loci
      have not been compared with regard to sequence diversity or locus specificity.
      Here, we report eight new B-F alpha 1/alpha 2-coding sequences from broiler
      chicken MHC B haplotypes, and a unique recombinant between the two B-F loci. The
      new sequences were combined with existing B-F sequences from Leghorn and broiler
      haplotypes for analysis. On the basis of phylogenetic analysis and conserved
      sequence motifs, B-F sequences separated into two groups (Groups A and B),
      corresponding to B-FIV and B-FI locus, respectively. Every broiler haplotype had
      one B-F sequence in Group A and the second B-F sequence, if it existed, clustered
      in Group B. Group B (presumptive B-FI locus) sequences identified in broiler
      haplotypes resembled the human MHC class I HLA-C locus in their distinctive
      pattern of allelic polymorphism. Compared with B-FIV, B-FI alleles were less
      polymorphic and possessed a conserved locus-specific motif in the alpha1 helix,
      but nevertheless demonstrated evidence of diversifying selection. One B-FI alpha
      1/alpha 2-coding nucleotide sequence was completely conserved in four different
      broiler haplotypes, but each allele differed in the exon encoding the alpha 3
      domain.

PMID- 14731226
TI  - Identification of putative homology between horse microsatellite flanking
      sequences and cross-species ESTs, mRNAs and genomic sequences.
AB  - In this study the flanking sequences of 1534 horse microsatellites were used in a
      BLAST search to identify putative human-horse homologies. BLAST searches revealed
      129 flanking sequences with significant blastn matches [alignment scores (S) > or
      = 60 and sum probability values (E) < or = 3.0E-6], also, 25 of these produced
      significant blastx matches. To provide a reference point in the human genome the
      flanking sequences with matches were subjected to a BLAT search of the University
      of California Santa Cruz (UCSC) human genome assembly (July 2003 freeze). Eighty
      three of the flanking sequences showed high similarity to sequence of known or
      putative human genes and the remaining 46 demonstrated high similarity to human
      intragenic regions. Interestingly, 87 of the microsatellites showed conservation
      of the tandem repeat in addition to flanking regions. Overall, 41 of the
      microsatellites had been mapped in the horse and of these 37 localized to the
      expected syntenic location. The other four did not and represent new putative
      regions of human-horse synteny. The results of this study contribute 79 new
      putative human-horse homologies, increasing the density of markers on the human
      horse comparative map.

PMID- 14731227
TI  - The scurs locus in cattle maps to bovine chromosome 19.
AB  - Polled, or the absence of horns, is a desirable trait for many cattle breeders.
      However, the presence of scurs, which are small horn-like structures that are not
      attached to the skull, can lower the value of an animal. The scurs trait has been
      reported as sex influenced. Using a genome scan with 162 autosomal microsatellite
      markers genotyped across three full-sib families, the scurs locus was mapped near
      BMS2142 on cattle chromosome 19 (LOD = 4.21). To more precisely map scurs, the
      families from the initial analysis and three additional families were genotyped
      for 16 microsatellite markers and SNPs in three genes on chromosome 19. In this
      subsequent analysis, the scurs locus was mapped 4 cM distal of BMS2142 (LOD =
      4.46) and 6 cM proximal to IDVGA46 (LOD = 2.56). ALOX12 and MFAP4 were the
      closest genes proximal and distal, respectively, to the scurs locus. Three
      microsatellite markers on the X chromosome were genotyped across these six
      families but were not linked to scurs, further demonstrating that this trait was
      not sex linked. Because the polled locus has been mapped to the centromeric end
      of chromosome 1 and scurs has now been mapped to chromosome 19, these two traits
      are not linked in Bos taurus.

PMID- 14731228
TI  - An association study using AFLP markers and application to a beef cattle breeding
      population.
AB  - Using amplified fragment length polymorphism (AFLP) fingerprinting, selective
      genotyping was performed to determine if this method was effective for selecting
      superior breeding stock. Forty-eight cows with extreme genetic merit for beef
      marbling score (BMS) were selected from a population of Japanese Black cattle (n
      = 4462), including 25 with the highest for predicted breeding value (PBV) and 23
      with the lowest. Sixteen AFLP fragments were selected for further analysis based
      on fragment frequency differences between the high and low groups. A linear
      discriminant analysis using these AFLP fragments was applied in order to derive a
      discriminant function that classified the cows into high and low groups. Seven of
      the 16 fragments were included in the resulting function and the discriminant
      scores (general genetic values, GGV) of the 48 cows were calculated using the
      function. These cows were clearly separated into high and low groups by GGV with
      a correlation ratio of 0.91 (discriminative error of 2.1%). The same function was
      then applied to 121 additional cows that were randomly selected from the original
      population. A significant regression coefficient of GGV on BMS-PBV (R2 = 0.45)
      was obtained, which indicates that the GGV can be used as a selection criterion
      for BMS in this population. These results suggest that AFLP fingerprinting can be
      used for animal breeding without identifying the underlying genes affecting the
      trait of interest.

PMID- 14731229
TI  - Detection and characterization of SNPs useful for identity control and parentage
      testing in major European dairy breeds.
AB  - We propose the use of single nucleotide polymorphisms (SNPs) instead of
      polymorphic microsatellite markers for individual identification and parentage
      control in cattle. To this end, we present an initial set of 37 SNP markers
      together with a gender-specific SNP for identity control and parentage testing in
      the Holstein, Fleckvieh and Braunvieh breeds. To obtain suitable SNPs, a total of
      91.13 kb of random genomic DNA was screened yielding 531 SNPs. These, and 43
      previously identified SNPs, were subjected to the following selection criteria:
      (1) the frequency of the minor allele must be larger than 0.1 in at least two of
      the three examined breeds, and (2) markers should not be linked closely. Allele
      frequencies were estimated by analysing sequencing traces of pooled DNA or by
      genotyping individual DNA samples. The selected SNP loci were physically mapped
      by radiation hybrid mapping or by fluorescence in situ hybridization, and tested
      against the neutral mutation hypothesis. The presented marker set theoretically
      allows probabilities of identity less than 10(-13) for individual verification
      and exclusion powers exceeding 99.99% for parentage testing.

PMID- 14731230
TI  - Genetic markers applied in regression tree prediction models.
AB  - Classification and regression tree (CART) modelling was used to determine
      infectious hypodermal and haematopoietic necrosis virus (IHHNV) resistance and
      susceptibility in Penaeus stylirostris. In a previous study, eight random
      amplified polymorphic DNA (RAPD) markers and viral load values using real-time
      quantitative PCR were obtained and used as the training data set in order to
      create numerous regression tree models. Specifically, the genetic markers were
      used as categorical predictor variables and viral load values as the dependent
      response variable. To determine which model has the highest predictive accuracy
      for future samples, RAPD fingerprint data was generated from new Penaues
      stylirostris IHHNV resistant and susceptible individuals and used to test the
      regression models. The best performing tree was a four terminal node tree with
      three genetic markers as significant variables. Marker-assisted breeding
      practices may benefit from the creation of regression tree models that apply
      genetic markers as predictive factors. To our knowledge this is the first study
      to use RAPD markers as predictors within a CART prediction model to determine
      viral susceptibility.

PMID- 14731231
TI  - Development and linkage relationships for new microsatellite markers of the sea
      bass (Dicentrarchus labrax L.).
AB  - Twenty-eight polymorphic microsatellites were isolated from the sea bass,
      Dicentrarchus labrax, using a microsatellite enrichment protocol and selective
      hybridization with oligonucleotide probes. Analysis for these markers and 11
      recently described microsatellites of D. labrax found linkage between 26 loci and
      revealed eight linkage groups.

PMID- 14731232
TI  - FISH mapping and sequence analysis of 87 porcine BAC clones.
AB  - Ninety-one bacterial artificial chromosomes (BAC) clones, selected effectively at
      random from our library, were used as probes for fluorescence in situ
      hybridization. Of these, 87 clones gave a specific signal in one, two or three
      different pair(s) of swine metaphase chromosomes. The ends of 35 BAC clones were
      sequenced in order to obtain information for comparative mapping. Fifteen of them
      gave useful comparative mapping information.

PMID- 14731233
TI  - A radiation hybrid map of chicken chromosome 15.
AB  - We have constructed a radiation hybrid (RH) map of chicken chromosome (GGA) 15.
      This map can be used as a resource to efficiently map genes to this chromosome.
      The map has been developed using a 6000 rad chicken-hamster whole-genome
      radiation hybrid panel (ChickRH6). In total, six microsatellite loci, 18 sequence
      tagged sites (STSs) from BAC end sequences and 11 genes were typed on the panel.
      The initial framework map comprised eight markers, and an additional 23 markers
      were then added to generate the final map. The total map length was 334
      centiRay6000 (cR6000). The estimated retention frequency for the data set was
      18%. Using an estimated physical length of 21 Mb, the ratio between cR6000 and
      physical distance over GGA15 was estimated to be 0.063 Mb/cR6000. The present map
      increases the marker density and the marker resolution on GGA15 and enables fast
      mapping of new chicken genes homologous to genes from human chromosomes 12 and
      22.

PMID- 14731234
TI  - Radiation hybrid mapping of the pig ALDOA, ALDOB and ALDOC genes to SSC3, SSC1
      and SSC12.

PMID- 14731235
TI  - Assignment of the chicken glycoprotein hormones, alpha polypeptide (CGA) gene to
      chromosome 3.

PMID- 14731236
TI  - Radiation hybrid mapping of 75 previously unreported equine microsatellite loci.

PMID- 14731237
TI  - Assignment of the phosphoglycerate kinase 2 (PGK2) gene to porcine chromosome
      7q14-q15 by fluorescence in situ hybridization and by analysis of somatic cell
      and radiation hybrid panels.

PMID- 14731238
TI  - Linkage mapping and expression analyses of a novel gene, placentally expressed
      transcript 1 (PLET1) in the pig.

PMID- 14731239
TI  - DNA sequence, polymorphism, and mapping of luteinizing hormone receptor fragment
      (LHCGR) gene in Great Dane dogs.

PMID- 14731240
TI  - Identification of two polymorphic microsatellites in a canine BAC clone
      harbouring a putative canine MAOA gene.

PMID- 14731242
TI  - Cleansing, dehydrating, barrier-damaging and irritating hyperaemising effect of
      four detergent brands: comparative studies using standardised washing models.
AB  - BACKGROUND AND PROBLEM: It is well known that the damaging effect of surfactants
      on the stratum corneum varies according to the surfactant used. The present
      investigations aim to compare four standard commercial cleansing solutions
      (Esemptan Cleansing Lotion, Stephalen Shower Gel, Manipur Antimicrobial Cleansing
      Solution and Tork Mevon 55 Liquid Soap) with respect to their cleansing and skin
      barrier-damaging effects. MATERIAL AND METHODS: The cleansing effect of the
      solutions was determined in relation to their concentrations in a first
      experimental series involving 15 subjects using a standardised test method. The
      product concentrations with the most divergent cleansing effects were tested for
      their dehydrating (corneometry), epidermal barrier-damaging (TEWL) and irritating
      effects (laser Doppler) in a standardised washing test. In a second experimental
      series, the concentration used for the cleansing solutions was based on the
      quantity of cleansing solution obtained from dispenser actuations (six
      actuations/L). These concentrations were used to test the cleansing and damaging
      effect on the stratum corneum using the same methods as in the first experimental
      series. RESULTS: There were no significant differences in the first experimental
      series. In the second experimental series, Stephalen Shower Gel showed
      disadvantages in terms of a small cleansing effect, but without evidence of a
      smaller stratum corneum-damaging effect, and Tork Mevon 55 Liquid Soap showed
      advantages in terms of a smaller stratum corneum-damaging effect, but without
      evidence of a smaller cleansing effect. CONCLUSIONS: These studies showed that
      the relationship between the cleansing and the damaging effect on the stratum
      corneum can be properly assessed only by testing different concentrations.
      Furthermore, this experimental approach allowed to differentiate the four tested
      cleansing solutions.

PMID- 14731243
TI  - Barrier repair in chronic plaque-type psoriasis.
AB  - PURPOSE: To investigate barrier repair after mild trauma in lesional skin of
      psoriasis patients with chronic plaque-type disease and to compare this with non
      involved psoriatic skin and normal controls. METHODS: Transepidermal water loss
      (TEWL) readings were taken from involved psoriatic skin and non-involved skin of
      psoriasis patients as well as the skin of normal controls. Three readings were
      performed at each site: the basal state, immediately after 20 tape strippings and
      1 week post stripping. RESULTS: Higher baseline, post-stripping and 1-week
      recovery TEWL readings in psoriatic-involved skin compared to non-involved and
      normal control skin. No significant difference in barrier recovery rate in
      psoriatic-involved skin compared to non-involved and normal control. CONCLUSION:
      Although there appears to be a derangement of barrier function in lesional skin
      of psoriasis patients compared to non-lesional skin and the skin of healthy
      controls, the barrier recovery function of lesional psoriatic skin is still fully
      operational.

PMID- 14731244
TI  - In vivo quantitative analysis of the effect of hydration (immersion and Vaseline
      treatment) in skin layers using high-resolution MRI and magnetisation transfer
      contrast.
AB  - BACKGROUND/AIMS: Many claims are made as to the efficacy of topical preparations
      in moisturising the skin, yet most of these claims cannot be substantiated by
      scientific study for the skin layers beneath the stratum corneum, and yield no
      information on the remainder of the epidermis and dermis. This argues for an in
      vivo quantitative method for measuring the effect of water loading extended to
      various layers of the skin. METHODS: Detailed high-resolution in vivo MRI studies
      of hydration and dehydration of finger pad skin layers were conducted on one
      normal subject using two moisturisation methods (topical white soft paraffin
      (Vaseline) and water immersion). The dehydration study was carried out
      immediately following removal from prolonged skin moisturisation. Inter
      individual variability for skin hydration (group study) was studied in seven
      healthy volunteers at 0 and 7 h hydration with Vaseline. Location dependence in
      skin hydration was investigated on the same subject by looking into the hydration
      of forearm and finger pad skin. System stability and measurement reproducibility
      was verified through a detailed phantom study. RESULTS: Images of normal and
      hydrated human skin were obtained in vivo at voxel dimensions of 50 micromx150
      micromx1000 microm. The effect of hydration and dehydration as a function of
      exposure to moisturiser (i.e. water and Vaseline) on the image signal intensity,
      observed T1, and interaction of free and bound water in specific tissues were
      identified and correlated with existing physiological knowledge. Swelling of
      stratum corneum due to hydration was expressed as an in vivo model of tissue
      hydration. CONCLUSION: Results of the dehydration study showed that the changes
      due to the previous hydration of the skin are reversible for all skin layers. For
      both moisturisation methods (i.e. Vaseline and skin bathing), the effects of
      hydration and dehydration on the skin were similar. The trends of the MRI
      parameters for finger pad and arm skin were similar. The group study showed low
      inter-subject variability of hydration on stratum corneum and epidermis.

PMID- 14731245
TI  - Real-time spatial compound ultrasound imaging of skin.
AB  - PURPOSE: The aim of our study was to evaluate the potential of real-time spatial
      compound imaging (RTSCI) in dermatology. MATERIALS AND METHODS: An ATL 5000
      SonoCT equipped with compact linear 15-7 MHz and linear 12-5 MHz transducers was
      obtained for skin visualization in a group of dermatological patients with
      various skin diseases. RESULTS: Thirty-four people participated: 21 patients with
      various skin diseases and 13 persons with normal skin. The mean age was 43.4
      years. For many diseases, RTSCI gave useful information about the lesional
      structure, thickness and relationship with surrounding structures. CONCLUSION:
      RTSCI allows objective, accurate, noninvasive and easy measurements of several
      parameters of skin morphology. It is useful in clinical trials, for evaluation of
      the effects of therapy, for preoperative evaluation of dermatological lesions,
      and enables visualization of subclinical and deep lesions, giving physicians the
      possibility of starting treatment before disease intensity increases. However,
      even such highly advanced ultrasound cannot completely substitute the clinical
      dermatological approach and the occasional need for histological diagnosis. This
      new method may, however, become an important adjunct method for the study of skin
      lesions.

PMID- 14731246
TI  - Measurement of hydration in the stratum corneum with the MoistureMeter and
      comparison with the Corneometer.
AB  - BACKGROUND/PURPOSE: MoistureMeter is a novel capacitive device for measuring the
      hydration of stratum corneum (SC). The capacitor 'plates' are formed by the probe
      material and the well-conducting epidermal-dermal skin layers, while the dry
      layer of SC acts as an 'insulator' of the capacitor. Due to this measurement
      principle, the measurement depth is not constant, but equal to the thickness of
      the dry layer of SC. The present study was undertaken to test the MoistureMeter
      SC-2 in an experimental setup simulating the uppermost skin structure. The
      sensitivity of the MoistureMeter was compared with a conventional device
      Corneometer CM 820 in eight healthy volunteers. METHODS: The experimental setup
      consisted of a polyethene foil simulating SC and a mixture of cellulose and
      saline simulating the underlying skin layers with a high water content. The
      hydration of SC of volar forearm was measured in eight healthy volunteers both
      with the MoistureMeter SC-2 and Corneometer CM 820 after the application of three
      different skin formulations: base, base plus salt (2 wt% NaCl), base plus salt
      and glycerin (5 wt%). In the sorption-desorption test, the skin was wetted with a
      drop of water and the dehydration was followed with both devices for 2 min.
      RESULTS: The test with the experimental setup agreed with the results predicted
      by the mathematical capacitance model. The hydration values of the MoistureMeter
      SC-2 and Corneometer CM 820 correlated well (R=0.75), but the relative range of
      readings with the MoistureMeter was approximately three times larger than with
      Corneometer. The MoistureMeter was insensitive for the salt (2 wt% NaCl) of the
      formulation and differentiated the hydration effect of glycerin better than the
      Corneometer. In the sorption-desorption test, the MoistureMeter demonstrated the
      individual differences between the volunteers, whereas with the Corneometer the
      differences were minimal. CONCLUSION: The capacitive measuring principle of the
      MoistureMeter was demonstrated in an experimental arrangement. Although both
      instruments yielded equivalent data with the base formulation, the MoistureMeter
      was a more sensitive device than the Corneometer CM 820 and independent of added
      salt in the formulations.

PMID- 14731247
TI  - Do ethnicity and gender have an impact on pain thresholds in minor dermatologic
      procedures? A study on thermal pain perception thresholds in Asian ethinic
      groups.
AB  - BACKGROUND AND OBJECTIVES: The perception of pain is a personal experience
      influenced by many factors, including genetic, ethnic and cultural issues.
      Understanding these perceptions is especially important in dermatologic patients
      undergoing minor surgical operations and who often differ in their pain response
      to surgical treatments. Little is known about how these differences affect the
      perception of experimental pain. The purpose of this study was to determine
      experimental pain perception differences in three distinct East Asian ethnic
      populations. METHODS: Pain thresholds were examined with a psychophysical
      computerized quantitative thermal sensory testing device (TSA 2001) in healthy
      volunteers recruited from three different Asian ethnic groups. Using the methods
      of limits, experimental pain perception threshold was measured on the forehead
      and volar aspect of the forearm in 49 healthy subjects. The measurements were
      then repeated after skin barrier perturbation with adhesive tape stripping of the
      stratum corneum. All three ethnic groups were analyzed separately with respect to
      age, gender educational level and skin type. RESULTS: A total of 20 Chinese, 14
      Malay and 15 Indian subjects completed the study. Thermal pain thresholds were
      similar in all three ethnic groups before and after tape strippings. No
      significant differences were noted between genders. CONCLUSIONS: Using
      quantitative sensory thermal testing, we demonstrated that no significant
      differences in pain occur between different races and genders.

PMID- 14731248
TI  - Assessment of pigmented skin lesions in terms of blood perfusion estimates.
AB  - BACKGROUND/AIMS: Cutaneous malignant melanoma is a disease of increasing clinical
      and economical importance. The prognosis is good with early diagnosis. The chief
      differential diagnosis is benign melanocytic naevus, a common lesion in
      Caucasians. Attempts have been made to use bioengineering techniques to aid in
      the initial diagnosis. The present study proposes a method of extracting possibly
      discriminative blood perfusion properties in pigmented skin lesions by combining
      information on the lesions' blood perfusion with optical or visual information of
      their spatial extent. METHODS: A total of 46 blood perfusion measurements were
      performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three
      histologically proven malignant melanomas, four histologically proven benign
      naevi and fifteen naevi assessed by two specialist dermatologists as being
      benign. Laser Doppler perfusion imaging gave two different types of two
      dimensional data sets (64x64 pixels), one representing the total backscattered
      light intensity at each measurement point (TLI image) and the second
      corresponding to perfusion values. The boundaries of each examined lesion were
      derived from the TLI image employing greyscale thresholding, thus resulting in an
      estimated region of interest (ROI) approximating the optical extent of the
      lesion. The ROI was superimposed on the perfusion image and extraction of
      perfusion features was then performed. RESULTS: The processing of the TLI images
      was successful in delineating the lesions' boundaries. The first hypothesis that
      the mean perfusion quotients in MM and benign naevi are equal could not be
      rejected at the chosen 5% level of significance. The second hypothesis that the
      mean percent-age of elevated perfusion values (image pixels) within the ROI shows
      no difference between MM and benign naevi could be rejected at a 5% level of
      significance. CONCLUSIONS: This study has presented a method of extracting blood
      perfusion parameters of pigmented skin lesions by combining blood perfusion
      information with information on the lesion's optical extent. The proposed method
      of presenting data could prove to be a useful discriminative adjunct in the
      assessment of pigmented skin lesions.

PMID- 14731249
TI  - Visual evaluation in vivo of 'complexion radiance' using the C.L.B.T. sensory
      methodology.
AB  - PURPOSE: The aim of this study was to develop a new technique enabling visual
      evaluation in vivo of 'complexion radiance' based on sensory analysis, and to
      apply this methodology to a practical case. METHODS: This evaluation, conducted
      by trained assessors, was based on a visual analysis in vivo of the following
      seven descriptors, clearly defined by consensus: a red-pink, olive, beige, and
      light-pink skin coloring (C), as well as the luminosity (L), brightness (B), and
      transparency (T) of each subject's facial skin. The scoring of perceived skin
      descriptor intensity was made possible with the help of structured and analogical
      scales. Once the assessors were considered to be accurate and repeatable, a
      method was designed to evaluate a cosmetic product's effect on complexion
      radiance. The study was conducted on 20 healthy female subjects, between 20 and
      35 years of age, who met the 'dull complexion' criteria. Product 'A' (Oligo 25,
      Laboratoires Vichy, Asnieres, France), formulated to improve 'complexion
      radiance,' was applied by each subject for 28 days, once a day in the morning, in
      a homogeneous fashion over the entire face, using a standard quantity and a
      specific way of massaging the product in. The clinical parameters were evaluated
      at T0, T+1 h, and at T+28 days. This test was a non-comparative open study and
      each subject served as her own reference. RESULTS: One hour after its
      application, product A produced an immediate significant effect by decreasing the
      complexion's 'olive' skin cast and improving its 'light-pink' coloring, its
      'luminosity,' and 'brightness.' The data concerning the long-term effect of
      product A following 28 days of application showed that there was significant
      improvement in these first four descriptors, while the 'beige' skin coloring was
      ultimately diminished in addition. CONCLUSION: This in vivo C.L.B.T. trade mark
      sensory methodology is a technique enabling the visual evaluation of a product's
      multi-factorial claim that it improves 'the complexion's radiance.' It made it
      possible to show, in a reliable and repeatable fashion, the efficacy of a
      cosmetic product in improving the 'radiance of the complexion' of members of a
      test panel. This methodology also substantiated the immediate and long-term
      effects produced by product A, which made the skin pinker and less sallow, more
      luminous, more uniform (skin coloring), more regular (skin texture), and then
      lighter. To conclude, five descriptors out of the seven determining complexion
      radiance were improved.

PMID- 14731250
TI  - Ultrasonographic subepidermal low-echogenic band, dependence of age and body
      site.
AB  - BACKGROUND/PURPOSE: The presence of an age-dependent subepidermal low-echogenic
      band (SLEB) is well established at specific body sites. Several studies have also
      proposed it to be a marker of photoaging, but only few studies have included
      children in their material, and UVR exposure has predominantly been evaluated as
      differences between body sites with different UVR exposure. The aim of this study
      was to further investigate the existence of SLEB and exploring its relation to
      both age and body site/UVR exposure. METHODS: In all 137 healthy volunteers from
      4 to 68 years of age were included. In vivo high-frequency ultrasonography (B
      mode, 20 MHz) was obtained from sun-exposed and sun-protected skin in a period
      with negligible environmental exposure to solar UVR. The SLEB was evaluated both
      visually and quantitatively. RESULTS: We found a significant correlation between
      visual scoring of SLEB and dermal echogenicity, which supports the usefulness of
      SLEB scoring. We found that the grade (existence and development) of SLEB
      increased significantly with age at both the forehead and at the dorsal aspect of
      the forearm, where a well-defined SLEB was absent in children and present in over
      50% of adults above the age of 40 years. No such age dependence was found either
      at the buttock or at the shoulder, and remarkably a well-defined SLEB was present
      in 37% of the adolescents at the buttock. CONCLUSION: These results indicate that
      the age-related increase in SLEB grade at highly sun-exposed body sites might be
      attributed to UVR exposure. The presence of SLEB in both the young and at the sun
      protected buttock points to a multifactorial etiology, where anatomical
      differences may play an important role as well as water content. SLEB might not
      be a very sensitive and specific marker of photoaging.

PMID- 14731251
TI  - Correlation between laser Doppler perfusion imaging and visual scoring of patch
      test sites in subjects with experimentally induced allergic and irritant contact
      reactions.
AB  - PURPOSE: To compare laser Doppler perfusion imaging (LDPI) measurements in
      experimentally induced allergic contact reactions and irritant contact reactions.
      The degree of correlation between visual scores and LDPI measurements was also
      studied. METHODS: Fifteen patients with known contact allergy to nickel or
      fragrance were patch tested with nickel sulfate 5% pet., fragrance mix 8% pet.,
      sodium lauryl sulfate (SLS) 0.5% pet., SLS 1.0% pet. and two empty control
      chambers. Visual readings and LDPI measurements were taken at 0, 48 and 96 h.
      RESULTS: There was a positive correlation between visual scores and LDPI
      measurement in the nickel sulfate and fragrance mix patch test sites. However, no
      correlation between visual scores and LDPI measurements was seen in the SLS 0.5%
      and SLS 1.0% patch test sites. There was no significant difference (P=0.125) in
      LDPI measurements between contact-allergic reactions and contact-irritant
      reactions. CONCLUSION: LDPI correlates with visual scoring in contact-allergic
      reactions, but not in irritant reactions. LDPI is not useful in distinguishing
      between allergic and irritant reactions.

PMID- 14731252
TI  - Morphometric assessment of nuclei in Bowen's disease and bowenoid papulosis.
AB  - BACKGROUND: Occasionally, Bowen's disease and bowenoid papulosis cannot be
      distinguished in microscopic finding. Their clinical presentations are quite
      different from one another. The purpose of this study was to evaluate the
      histological differences in Bowen's disease and bowenoid papulosis, by comparing
      the size and shape of nuclei, using image analysis system. METHODS: We performed
      morphometric assessment on 13 specimens of Bowen's disease and eight specimens of
      bowenoid papulosis using an image analysis system, and the following parameters
      were calculated, such as nuclear contour index (NCI), irregularities of nucleus
      (IN), form factor (form AR) and circulatory factor (form PE). RESULTS: For NCI,
      there were significant differences between the Bowen's disease and bowenoid
      papulosis, and IN also shows significant differences between these two dis-eases,
      showing that Bowen's disease has more corrugated or indented nucleus contour than
      bowenoid papulosis. In the parameter of form PE, there were significant
      differences between the two diseases, indicating that Bowen's disease has more
      oval-shaped nuclei than bowenoid papulosis. There were no significant differences
      in form factor between Bowen's disease and bowenoid pupulosis. CONCLUSIONS:
      Significant differences were found in the morphometric evaluation between Bowen's
      disease and bowenoid papulosis. The nuclei were larger, more oval and more
      irregular margins in Bowen's disease than bowenoid papulosis.

PMID- 14731253
TI  - Map-based cloning of a fertility restorer gene, Rf-1, in rice (Oryza sativa L.).
AB  - A rice nuclear gene, Rf-1, restores the pollen fertility disturbed by the BT-type
      male sterile cytoplasm, and is widely used for commercial seed production of
      japonica hybrid varieties. Genomic fragments carrying Rf-1 were identified by
      conducting chromosome walking and a series of complementation tests. Isolation
      and analysis of cDNA clones corresponding to the fragments demonstrated that Rf-1
      encodes a mitochondrially targeted protein containing 16 repeats of the 35-aa
      pentatricopeptide repeat (PPR) motif. Sequence analysis revealed that the
      recessive allele, rf-1, lacks one nucleotide in the putative coding region,
      presumably resulting in encoding a truncated protein because of a frame shift.
      Rice Rf-1 is the first restorer gene isolated from cereal crops that has the
      property of reducing the expression of the cytoplasmic male sterility (CMS)
      associated mitochondrial gene like many other restorer genes. The present
      findings may facilitate not only elucidating the mechanisms of male sterility by
      the BT cytoplasm and its restoration by Rf-1 but also isolating other restorer
      genes from cereal crops, especially rice.

PMID- 14731254
TI  - HvDRF1 is involved in abscisic acid-mediated gene regulation in barley and
      produces two forms of AP2 transcriptional activators, interacting preferably with
      a CT-rich element.
AB  - Apetala2/ethylene-responsive factor (AP2/ERF) proteins are AP2 domain-containing
      transcription factors and form the second largest transcription factor family in
      plants. Biological functions of many of these AP2 proteins are still unknown.
      Here, we report the characterisation of a novel member of the AP2/ERF
      superfamily, dehydration-responsive factor 1 (HvDRF1) from barley, and its role
      in abscisic acid (ABA)-mediated gene regulation. The expression of HvDRF1 was
      upregulated in barley leaves and roots under drought, salt or ABA treatment, and
      in embryos during seed maturation. Three forms of HvDRF1 transcripts were
      produced through alternative splicing, two of which encoded AP2 proteins. This
      alternative splicing pattern was also observed in a wheat homologue gene, TaDRF1.
      Both of HvDRF1 AP2 proteins acted as transcriptional activators, capable of
      activating the promoter activity of an ABA-inducible HVA1s in barley. In vitro
      DNA-binding analysis using synthetic oligonucleotides revealed that HvDRF1 AP2
      protein bound preferably to a CT-rich element (T(T/A)ACCGCCTT). HvDRF1 activity
      on the activation of HVA1s expression in barley leaves was markedly enhanced by
      HvABI5 (a bZIP transcription factor), ABA or drought treatment. These results
      indicate that the HvDRF1 transcriptional activator co-operates with other ABA
      responsive factors in the upregulation of stress gene expression through an ABA
      dependent pathway.

PMID- 14731255
TI  - Arabidopsis ALF4 encodes a nuclear-localized protein required for lateral root
      formation.
AB  - Lateral root formation, the primary way plants increase their root mass, displays
      developmental plasticity in response to environmental changes. The aberrant
      lateral root formation (alf)4-1 mutation blocks the initiation of lateral roots,
      thus greatly altering root system architecture. We have positionally cloned the
      ALF4 gene and have further characterized its phenotype. The encoded ALF4 protein
      is conserved among plants and has no similarities to proteins from other
      kingdoms. The gene is present in a single copy in Arabidopsis. Using
      translational reporters for ALF4 gene expression, we have determined that the
      ALF4 protein is nuclear localized and that the gene is expressed in most plant
      tissues; however, ALF4 expression and ALF4's subcellular location are not
      regulated by auxin. These findings taken together with further genetic and
      phenotypic characterization of the alf4-1 mutant suggest that ALF4 functions
      independent from auxin signaling and instead functions in maintaining the
      pericycle in the mitotically competent state needed for lateral root formation.
      Our results provide genetic evidence that the pericycle shares properties with
      meristems and that this tissue plays a central role in creating the developmental
      plasticity needed for root system development.

PMID- 14731256
TI  - Gain-of-function and loss-of-function phenotypes of the protein phosphatase 2C
      HAB1 reveal its role as a negative regulator of abscisic acid signalling.
AB  - HAB1 was originally cloned on the basis of sequence homology to ABI1 and ABI2,
      and indeed, a multiple sequence alignment of 32 Arabidopsis protein phosphatases
      type-2C (PP2Cs) reveals a cluster composed by the four closely related proteins,
      ABI1, ABI2, HAB1 and At1g17550 (here named HAB2). Characterisation of transgenic
      plants harbouring a transcriptional fusion ProHAB1: green fluorescent protein
      (GFP) indicates that HAB1 is broadly expressed within the plant, including key
      target sites of abscisic acid (ABA) action as guard cells or seeds. The
      expression of the HAB1 mRNA in vegetative tissues is strongly upregulated in
      response to exogenous ABA. In this work, we show that constitutive expression of
      HAB1 in Arabidopsis under a cauliflower mosaic virus (CaMV) 35S promoter led to
      reduced ABA sensitivity both in seeds and vegetative tissues, compared to wild
      type plants. Thus, in the field of ABA signalling, this work represents an
      example of a stable phenotype in planta after sustained overexpression of a PP2C
      genes. Additionally, a recessive T-DNA insertion mutant of HAB1 was analysed in
      this work, whereas previous studies of recessive alleles of PP2C genes were
      carried out with intragenic revertants of the abi1-1 and abi2-1 mutants that
      carry missense mutations in conserved regions of the PP2C domain. In the presence
      of exogenous ABA, hab1-1 mutant shows ABA-hypersensitive inhibition of seed
      germination; however, its transpiration rate was similar to that of wild-type
      plants. The ABA-hypersensitive phenotype of hab1-1 seeds together with the
      reduced ABA sensitivity of 35S:HAB1 plants are consistent with a role of HAB1 as
      a negative regulator of ABA signalling. Finally, these results provide new
      genetic evidence on the function of a PP2C in ABA signalling.

PMID- 14731257
TI  - Papain protects papaya trees from herbivorous insects: role of cysteine proteases
      in latex.
AB  - Many plants contain latex that exudes when leaves are damaged, and a number of
      proteins and enzymes have been found in it. The roles of those latex proteins and
      enzymes are as yet poorly understood. We found that papain, a cysteine protease
      in latex of the Papaya tree (Carica papaya, Caricaceae), is a crucial factor in
      the defense of the papaya tree against lepidopteran larvae such as oligophagous
      Samia ricini (Saturniidae) and two notorious polyphagous pests, Mamestra
      brassicae (Noctuidae) and Spodoptera litura (Noctuidae). Leaves of a number of
      laticiferous plants, including papaya and a wild fig, Ficus virgata (Moraceae),
      showed strong toxicity and growth inhibition against lepidopteran larvae, though
      no apparent toxic factors from these species have been reported. When the latex
      was washed off, the leaves of these lactiferous plants lost toxicity. Latexes of
      both papaya and the wild fig were rich in cysteine-protease activity. E-64, a
      cysteine protease-specific inhibitor, completely deprived the leaves of toxicity
      when painted on the surface of papaya and fig leaves. Cysteine proteases, such as
      papain, ficin, and bromelain, all showed toxicity. The results suggest that plant
      latex and the proteins in it, cysteine proteases in particular, provide plants
      with a general defense mechanism against herbivorous insects.

PMID- 14731258
TI  - Organelle inheritance in plant cell division: the actin cytoskeleton is required
      for unbiased inheritance of chloroplasts, mitochondria and endoplasmic reticulum
      in dividing protoplasts.
AB  - Nuclear inheritance is highly ordered, ensuring stringent, unbiased partitioning
      of chromosomes before cell division. In plants, however, little is known about
      the analogous cellular processes that might ensure unbiased inheritance of non
      nuclear organelles, either in meristematic cell divisions or those induced during
      the acquisition of totipotency. We have investigated organelle redistribution and
      inheritance mechanisms during cell division in cultured tobacco mesophyll
      protoplasts. Quantitative analysis of organelle repositioning observed by
      autofluorescence of chloroplasts or green fluorescent protein (GFP), targeted to
      mitochondria or endoplasmic reticulum (ER), demonstrated that these organelles
      redistribute in an ordered manner before division. Treating protoplasts with
      cytoskeleton-disrupting drugs showed that redistribution depended on actin
      filaments (AFs), but not on microtubules (MTs), and furthermore, that an intact
      actin cytoskeleton was required to achieve unbiased organelle inheritance.
      Labelling the actin cytoskeleton with a novel GFP-fusion protein revealed a
      highly dynamic actin network, with local reorganisation of this network itself,
      appearing to contribute substantially to repositioning of chloroplasts and
      mitochondria. Our observations show that each organelle exploits a different
      strategy of redistribution to ensure unbiased partitioning. We conclude that
      inheritance of chloroplasts, mitochondria and ER in totipotent plant cells is an
      ordered process, requiring complex interactions with the actin cytoskeleton.

PMID- 14731259
TI  - Trafficking of the plant potassium inward rectifier KAT1 in guard cell
      protoplasts of Vicia faba.
AB  - Trafficking of K+ inward (Kin+) rectifying channels was analyzed in guard cells
      of Vicia faba transfected with the Kin+ rectifier from Arabidopsis thaliana KAT1
      fused to the green fluorescent protein (GFP). Confocal images and whole-cell
      patch-clamp measurements confirmed the incorporation of active KAT1 channels into
      the plasma membrane of transfected guard cell protoplasts. The Kin+ rectifier
      current density of the plasma membrane was much larger in transfected protoplasts
      than in wild-type (wt) protoplasts. This shows a coupling between K+ channel
      synthesis and incorporation of the channel into the plasma membrane. Pressure
      driven increase and decrease in surface area led to the incorporation and removal
      of vesicular membrane carrying active Kin+ rectifier in wt and transfected
      protoplasts. These vesicular membranes revealed a higher channel density than the
      plasma membrane, suggesting that Kin+ rectifier remains in clusters during
      trafficking to and from the plasma membrane. The observed results can be
      explained by a model illustrating that vesicles of a pre-plasma membrane pool
      carry K+ channels preferentially in clusters during constitutive and pressure
      driven exo- and endocytosis.

PMID- 14731260
TI  - Identification of a mitochondrial external NADPH dehydrogenase by overexpression
      in transgenic Nicotiana sylvestris.
AB  - The plant respiratory chain contains a complex setup of non-energy conserving
      NAD(P)H dehydrogenases, the physiological consequences of which are highly
      unclear. An expression construct for the potato (Solanum tuberosum L., cv.
      Desiree) ndb1 gene, a homologue of bacterial and fungal type II NAD(P)H
      dehydrogenases, was introduced into Nicotiana sylvestris. Transgenic lines with
      high transcript and protein levels for St-NDB1 had up to threefold increased
      activity of external NADPH dehydrogenase in isolated mitochondria as compared to
      the wild type (WT). In two lines, the external NADPH dehydrogenase activity was
      instead 10-fold decreased, indicating that the corresponding N. sylvestris gene
      had been suppressed. Activities of external and internal rotenone-insensitive
      NADH dehydrogenases were unchanged in the transgenic lines. The results
      demonstrate that the St-ndb1 encodes an external dehydrogenase specific for NADPH
      and dependent on calcium for activity. Transgenic lines overexpressing St-ndb1
      had specifically increased protein levels for alternative oxidase and uncoupling
      protein, as compared to the WT and one co-suppressing line. This indicates cross
      talk in the expressional control, or metabolic conditions influencing it, for the
      different categories of energy-dissipating proteins that bypass oxidative
      phosphorylation. The potential effects of external NADPH oxidation on other
      cellular processes are discussed.

PMID- 14731261
TI  - Definition and interactions of a positive regulatory element of the Arabidopsis
      INNER NO OUTER promoter.
AB  - INNER NO OUTER (INO) expression is limited to the abaxial cell layer of the
      incipient and developing outer integument in Arabidopsis ovules. Using deletion
      analysis of the previously defined INO promoter (P-INO), at least three distinct
      regions that contribute to the endogenous INO expression pattern were identified.
      One such positive element, designated POS9, which comprises at least three
      distinct subelements, was found to include sufficient information to duplicate
      the INO expression pattern when four or more copies were used in conjunction with
      a heterologous minimal promoter. While known regulators of INO, including INO,
      SUPERMAN, BELL1, and AINTEGUMENTA, did not detectably interact with POS9 in yeast
      one-hybrid assays, two groups of proteins that interact specifically with POS9
      were identified in one-hybrid library screens. Members of one group include C2H2
      zinc finger motifs. Members of the second group contain a novel, conserved DNA
      binding region and were designated the BASIC PENTACYSTEINE (BPC) proteins on the
      basis of conserved features of this region. The BPC proteins are nuclear
      localized and specifically bind in vitro to GA dinucleotide repeats located
      within POS9. The widespread expression patterns of the BPCs and the large number
      of GA repeat potential target sequences in the Arabidopsis genome indicate that
      BPC proteins may affect expression of genes involved in a variety of plant
      processes.

PMID- 14731262
TI  - Ecdysone agonist-inducible expression of a coat protein gene from tobacco mosaic
      virus confers viral resistance in transgenic Arabidopsis.
AB  - Constitutive expression of a gene encoding tobacco mosaic virus (TMV) coat
      protein (CP) in transgenic plants confers resistance to infection by TMV and
      related tobamoviruses. Here, we examined resistance to TMV by temporal and
      quantitative control of TMV Cg CP (CgCP) gene expression using a simple,
      methoxyfenozide-inducible system in Arabidopsis plants. By soil drenching with a
      commercial ecdysone agonist (Intrepid-2F/methoxyfenozide), most transgenic lines
      were induced from undetectable levels of gene expression to protein levels from
      0.05 to 0.8% (w/w) of CgCP. This corresponds to up to four times the amount of CP
      produced by the constitutive cauliflower mosaic virus (CaMV) double 35S promoter.
      CgCP transcripts were induced by 700-fold, without changing the expression
      patterns of pathogenesis-related (PR) genes. The high level of accumulation of
      CgCP was sufficient to produce large amounts of virus-like particles that
      accumulate in large aggregates throughout the cells. In virus challenge assays,
      treatment with Intrepid-2F prior to TMV infection resulted in high levels of
      viral resistance, while no treatment or treatment with the inducer following
      infection did not confer resistance. This report demonstrates chemically
      controlled disease resistance and confirms the utility of the ecdysone agonist
      inducible system under greenhouse conditions.

PMID- 14731263
TI  - Development of a luciferase reporter gene, luxCt, for Chlamydomonas reinhardtii
      chloroplast.
AB  - Luciferase reporter genes have been successfully used in a variety of organisms
      to examine gene expression in living cells, but are yet to be successfully
      developed for use in chloroplast. Green fluorescent protein (gfp) has been used
      as a reporter of chloroplast gene expression, but because of high auto
      fluorescence, very high levels of GFP accumulation are required for visualization
      in vivo. We have developed a luciferase reporter for chloroplast by synthesizing
      the two-subunit bacterial luciferase (lux)AB, as a single fusion protein in
      Chlamydomonas reinhardtii chloroplast codon bias. We expressed a chloroplast
      luciferase gene, luxCt, in C. reinhardtii chloroplasts under the control of the
      ATPase alpha subunit (atpA) or psbA promoter and 5' untranslated regions (UTRs)
      and the rubisco large subunit (rbcL) 3' UTR. We show that luxCt is a sensitive
      reporter of chloroplast gene expression, and that luciferase activity can be
      measured in vivo using a charge coupled device (CCD) camera or in vitro using a
      luminometer. We further demonstrate that luxCt protein accumulation, as measured
      by Western blot analysis, is proportional to luminescence, as determined both in
      vivo and in vitro, and that luxCt is capable of reporting changes in chloroplast
      gene expression during a dark to light shift. These data demonstrate the utility
      of the luxCt gene as a versatile and sensitive reporter of chloroplast gene
      expression in living cells.

PMID- 14731265
TI  - A GFP-based assay reveals a role for RHD3 in transport between the endoplasmic
      reticulum and Golgi apparatus.
AB  - We describe the use of a secreted form of Aequoria victoria green fluorescent
      protein (secGFP) in a non-invasive live cell assay of membrane traffic in
      Arabidopsis thaliana. We show that in comparison to GFP-HDEL, which accumulates
      in the endoplasmic reticulum (ER), secGFP generates a weak fluorescence signal
      when transported to the apoplast. The fluorescence of secGFP in the apoplast can
      be increased by growth of seedlings on culture medium buffered at pH 8.1,
      suggesting that apoplastic pH is responsible, at least in part, for the low
      fluorescence intensity of seedlings expressing secGFP. Inhibition of secGFP
      transport between the ER and plasma membrane (PM), either by Brefeldin A (BFA)
      treatment or by genetic intervention results in increased intracellular secGFP
      accumulation accompanied by an increase in the secGFP fluorescence intensity.
      secGFP thus provides a valuable tool for forward and reverse genetic analysis of
      membrane traffic and endomembrane organisation in Arabidopsis. Using this assay
      for quantitative sublethal perturbation of secGFP transport, we identify a role
      for root hair defective 3 (RHD3) in transport of secreted and Golgi markers
      between the ER and the Golgi apparatus.

PMID- 14731266
TI  - Tomographic reconstruction of treponemal cytoplasmic filaments reveals novel
      bridging and anchoring components.
AB  - An understanding of the involvement of bacterial cytoplasmic filaments in cell
      division requires the elucidation of the structural organization of those
      filamentous structures. Treponemal cytoplasmic filaments are composed of one
      protein, CfpA, and have been demonstrated to be involved in cell division. In
      this study, we used electron tomography to show that the filaments are part of a
      complex with a novel molecular organization that includes at least two distinct
      features decorating the filaments. One set of components appears to anchor the
      filaments to the cytoplasmic membrane. The other set of components appears to
      bridge the cytoplasmic filaments on the cytoplasmic side, and to be involved in
      the interfilament spacing within the cell. The filaments occupy between 3 and 18%
      of the inner surface of the cytoplasmic membrane. These results reveal a novel
      filamentous molecular organization of independent filaments linked by bridges and
      continuously anchored to the membrane.

PMID- 14731267
TI  - The tetraspanin BcPls1 is required for appressorium-mediated penetration of
      Botrytis cinerea into host plant leaves.
AB  - Animal tetraspanins are membrane proteins controlling cell adhesion, morphology
      and motility. In fungi, the tetraspanin MgPls1 controls an appressorial function
      required for the penetration of Magnaporthe grisea into host plants. An
      orthologue of MgPLS1, BcPLS1, was identified in the necrotrophic fungal plant
      pathogen Botrytis cinerea. We constructed a Bcpls1::bar null mutant by targeted
      gene replacement. Bcpls1::bar is not pathogenic on intact plant tissues of bean,
      tomato or rose, but it infects wounded plant tissues. Both wild type and
      Bcpls1::bar differentiate appressoria on plant and artificial surfaces, a process
      involving an arrest of polarized growth, apex swelling and its cell wall
      reinforcement. Although wild-type appressoria allowed the penetration of the
      fungus into the host plant within 6-12 h, no successful penetration events were
      observed with Bcpls1::bar, suggesting that its appressoria are not functional. An
      eGFP transcriptional fusion showed that BcPLS1 was specifically expressed in
      conidia, germ tubes and appressoria during host penetration. Our results indicate
      that BcPLS1 is required for the penetration of B. cinerea into intact host
      plants. The defect in pathogenicity of Bcpls1::bar also demonstrates that
      functional B. cinerea appressoria are required for a successful penetration
      process. As Bcpls1::bar and Mgpls1 Delta::hph penetration defects are similar,
      fungal tetraspanins are likely to be required for an essential appressorial
      function widespread among fungi.

PMID- 14731268
TI  - The HCC-domain of botulinum neurotoxins A and B exhibits a singular ganglioside
      binding site displaying serotype specific carbohydrate interaction.
AB  - Tetanus and botulinum neurotoxins selectively invade neurons following binding to
      complex gangliosides. Recent biochemical experiments demonstrate that two
      ganglioside binding sites within the tetanus neurotoxin HC-fragment, originally
      identified in crystallographic studies to bind lactose or sialic acid, are
      required for productive binding to target cells. Here, we determine by mass
      spectroscopy studies that the HC-fragment of botulinum neurotoxins A and B bind
      only one molecule of ganglioside GT1b. Mutations made in the presumed ganglioside
      binding site of botulinum neurotoxin A and B abolished the formation of these HC
      fragment/ganglioside complexes, and drastically diminished binding to neuronal
      membranes and isolated GT1b. Furthermore, correspondingly mutated full-length
      neurotoxins exhibit significantly reduced neurotoxicity, thus identifying a
      single ganglioside binding site within the carboxyl-terminal half of the HC
      fragment of botulinum neurotoxins A and B. These binding cavities are defined by
      the conserved peptide motif H...SXWY...G. The roles of tyrosine and histidine in
      botulinum neurotoxins A and B in ganglioside binding differ from those in the
      analogous tetanus neurotoxin lactose site. Hence, these findings provide valuable
      information for the rational design of potent botulinum neurotoxin binding
      inhibitors.

PMID- 14731269
TI  - R174 of Escherichia coli FtsZ is involved in membrane interaction and
      protofilament bundling, and is essential for cell division.
AB  - We investigated the interaction between FtsZ and the cytoplasmic membrane using
      inside-out vesicles. Comparison of the trypsin accessibility of purified FtsZ and
      cytoplasmic membrane-bound FtsZ revealed that the protruding loop between helix 6
      and helix 7 is protected from trypsin digestion in the latter. This hydrophobic
      loop contains an arginine residue at position 174. To investigate the role of
      R174, this residue was replaced by an aspartic acid, and FtsZ-R174D was fused to
      green fluorescent protein (GFP). FtsZ-R174D-GFP could localize in an FtsZ and in
      an FtsZ84(Ts) background at both the permissive and the non-permissive
      temperature, and it had a reduced affinity for the cytoplasmic membrane compared
      with wild-type FtsZ. FtsZ-R174D could also localize in an FtsZ depletion strain.
      However, in contrast to wild-type FtsZ, FtsZ-R174D was not able to complement the
      ftsZ84 mutation or the depletion strain and induced filamentation. In vitro
      polymerization experiments showed that FtsZ-R174D is able to polymerize, but that
      these polymers cannot form bundles in the presence of 10 mM CaCl2. This is the
      first description of an FtsZ mutant that has reduced affinity for the cytoplasmic
      membrane and does not support cell division, but is still able to localize. The
      mutant is able to form protofilaments in vitro but fails to bundle. It suggests
      that neither membrane interaction nor bundling is a requirement for initiation of
      cell division.

PMID- 14731270
TI  - Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene
      expression.
AB  - The formation of biofilm results in a major lifestyle switch that is thought to
      affect the expression of multiple genes and operons. We used DNA arrays to study
      the global effect of biofilm formation on gene expression in mature Escherichia
      coli K-12 biofilm. We show that, when biofilm is compared with the exponential
      growth phase, 1.9% of the genes showed a consistent up- or downregulation by a
      factor greater than two, and that 10% of the E. coli genome is significantly
      differentially expressed. The functions of the genes induced in these conditions
      correspond to stress response as well as energy production, envelope biogenesis
      and unknown functions. We provide evidence that the expression of stress envelope
      response genes, such as the psp operon or elements of the cpx and rpoE pathways,
      is a general feature of E. coli mature biofilms. We also compared biofilm with
      the stationary growth phase and showed that the biofilm lifestyle, although
      sharing similarities with the stationary growth phase, triggers the expression of
      specific sets of genes. Using gene disruption of 54 of the most biofilm-induced
      genes followed by a detailed phenotypic study, we validated the biological
      relevance of our analysis and showed that 20 of these genes are required for the
      formation of mature biofilm. This group includes 11 genes of previously unknown
      function. These results constitute a comprehensive analysis of the global
      transcriptional response triggered in mature E. coli biofilms and provide
      insights into its physiological signature.

PMID- 14731271
TI  - Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms.
AB  - Pseudomonas aeruginosa forms diverse matrix-enclosed surface-associated
      multicellular assemblages (biofilms) that aid in its survival in a variety of
      environments. One such biofilm is the pellicle that forms at the air-liquid
      interface in standing cultures. We screened for transposon insertion mutants of
      P. aeruginosa PA14 that were unable to form pellicles. Analysis of these mutants
      led to the identification of seven adjacent genes, named pel genes, the products
      of which appear to be involved in the formation of the pellicle's extracellular
      matrix. In addition to being required for pellicle formation, the pel genes are
      also required for the formation of solid surface-associated biofilms. Sequence
      analyses predicted that three pel genes encode transmembrane proteins and that
      five pel genes have functional homologues involved in carbohydrate processing.
      Microscopic and macroscopic observations revealed that wild-type P. aeruginosa
      PA14 produces a cellulase-sensitive extracellular matrix able to bind Congo red;
      no extracellular matrix was produced by the pel mutants. A comparison of the
      carbohydrates produced by the wild-type strain and pel mutants suggested that
      glucose was a principal component of the matrix material. Together, these results
      suggest that the pel genes are responsible for the production of a glucose-rich
      matrix material required for the formation of biofilms by P. aeruginosa PA14.

PMID- 14731272
TI  - The serine/threonine protein phosphatase SIT4 modulates yeast-to-hypha
      morphogenesis and virulence in Candida albicans.
AB  - SIT4 encodes the multifunctional catalytic subunit of a type 2A-related protein
      phosphatase of Saccharomyces cerevisiae and has been implicated in cell cycle
      regulation and nitrogen sensing. We have identified the Candida albicans
      homologue of SIT4, and we show that its disruption caused a significant reduction
      in general growth rate, in hyphal outgrowth and in virulence in a mouse infection
      model. These phenotypes were reversed by the reintroduction of the wild-type SIT4
      gene. We used glass DNA microarrays to measure the transcriptional profiles of
      6287 open reading frames in sit4 cells undergoing the yeast-to-hypha transition
      induced by serum. Although differential expression of many of the hyphae-specific
      genes was not affected by the SIT4 deletion, the transcription of two new hyphae
      induced genes, XOG1 and YNR67, was entirely reliant upon Sit4p. Both genes
      represent glucanases, indicating that SIT4 may play a role in controlling cell
      wall biogenesis. Furthermore, sit4 cells exhibited a reduced heat shock response
      to treatment with serum/37 degrees C, suggesting that SIT4 acts to co-ordinate
      the stress response signals during morphological switching. Finally, sit4 cells
      displayed reduced transcript levels for the genes encoding the Hog1p MAP kinase
      and several modulators of protein biosynthesis. Sit4p thus plays important roles
      during hyphal growth in Candida albicans through the regulation of cell wall
      biogenesis, osmosensing and protein translation.

PMID- 14731273
TI  - Crystal structure of the cytotoxic bacterial protein colicin B at 2.5 A
      resolution.
AB  - Colicin B (55 kDa) is a cytotoxic protein that recognizes the outer membrane
      transporter, FepA, as a receptor and, after gaining access to the cytoplasmic
      membranes of sensitive Escherichia coli cells, forms a pore that depletes the
      electrochemical potential of the membrane and ultimately results in cell death.
      To begin to understand the series of dynamic conformational changes that must
      occur as colicin B translocates from outer membrane to cytoplasmic membrane, we
      report here the crystal structure of colicin B at 2.5 A resolution. The crystal
      belongs to the space group C2221 with unit cell dimensions a = 132.162 A, b =
      138.167 A, c = 106.16 A. The overall structure of colicin B is dumbbell shaped.
      Unlike colicin Ia, the only other TonB-dependent colicin crystallized to date,
      colicin B does not have clearly structurally delineated receptor-binding and
      translocation domains. Instead, the unique N-terminal lobe of the dumbbell
      contains both domains and consists of a large (290 residues), mostly beta
      stranded structure with two short alpha-helices. This is followed by a single
      long ( approximately 74 A) helix that connects the N-terminal domain to the C
      terminal pore-forming domain, which is composed of 10 alpha-helices arranged in a
      bundle-type structure, similar to the pore-forming domains of other colicins. The
      TonB box sequence at the N-terminus folds back to interact with the N-terminal
      lobe of the dumbbell and leaves the flanking sequences highly disordered.
      Comparison of sequences among many colicins has allowed the identification of a
      putative receptor-binding domain.

PMID- 14731274
TI  - Receptor conformational changes enhance methylesterase activity during chemotaxis
      by Bacillus subtilis.
AB  - Addition and removal of the attractant asparagine causes methanol formation as a
      consequence of methylation and demethylation of conserved glutamate residues in
      the Bacillus subtilis chemotaxis receptor McpB C-terminal domain. We found that
      methanol was released on both addition and removal of asparagine even when the
      response regulator domain of CheB was removed (to produce CheB(141-357)). Thus,
      in undergoing the transition from unbound receptor to ligand-bound adapted
      receptor, the receptor must pass through a state of heightened susceptibility to
      demethylation by CheB that is independent of phosphorylation. The same result
      occurred when the aspartate phosphorylation site of CheB, Asp54, had been mutated
      to an asparagine residue, provided the enzyme was sufficiently induced. However,
      no methanol release was observed for an active site point mutant, cheB(S173C), in
      response to addition or removal of asparagine even when induced. Finally,
      methanol release was observed only for attractant addition in a mutant background
      lacking the coupling proteins, CheW and CheV, provided CheB(141-357) was present.
      Thus, on attractant addition, methanol must arise from a transient conformation
      of the receptor C-terminal domain that is an intrinsic property of the receptor;
      on attractant removal, however, methanol must arise from a different transient
      conformation, one dependent on the presence of coupling proteins.

PMID- 14731275
TI  - Cross-species hybridization of a Borrelia burgdorferi DNA array reveals infection
      and culture-associated genes of the unsequenced genome of the relapsing fever
      agent Borrelia hermsii.
AB  - The known genome sequence of Borrelia burgdorferi, an agent of Lyme borreliosis,
      was used to study the genetic content and gene expression in B. hermsii, another
      spirochete pathogen and a cause of relapsing fever. Cross-species hybridization
      of a DNA array representing 1628 open reading frames (ORF) of B. burgdorferi with
      genomic DNA of B. hermsii indicated that the latter organism has at least 81% of
      the chromosomal genes and 43% of the plasmid genes of B. burgdorferi. We then
      carried out quantitative hybridization of the arrays with multiple replicates of
      cDNA produced from B. hermsii cells growing in the blood of infected mice or in
      culture medium that was adjusted to the same pH, temperature and a spirochete
      density as infected blood. Of 642 B. burgdorferi ORFs hybridized by all
      replicates under both conditions, 12 (1.9%) demonstrated differential expression
      by a regularized t-test and stringent criteria. BBP07 and BBG30, two plasmid
      borne ORFs with the greatest measurable difference in expression between in vivo
      and in vitro conditions, putatively encode proteins of unknown function.
      Orthologues of BBP07 in B. hermsii were identified, and increased expression in
      infected mice was demonstrated by quantitative reverse-transcriptase polymerase
      chain reaction.

PMID- 14731276
TI  - Several distinct localization patterns for penicillin-binding proteins in
      Bacillus subtilis.
AB  - Bacterial cell shape is determined by a rigid external cell wall. In most non
      coccoid bacteria, this shape is also determined by an internal cytoskeleton
      formed by the actin homologues MreB and/or Mbl. To gain further insights into the
      topological control of cell wall synthesis in bacteria, we have constructed green
      fluorescent protein (GFP) fusions to all 11 penicillin-binding proteins (PBPs)
      expressed during vegetative growth of Bacillus subtilis. The localization of
      these fusions was studied in a wild-type background as well as in strains
      deficient in FtsZ, MreB or Mbl. PBP3 and PBP4a localized specifically to the
      lateral wall, in distinct foci, whereas PBP1 and PBP2b localized specifically to
      the septum. All other PBPs localized to both the septum and the lateral cell
      wall, sometimes with irregular distribution along the lateral wall or a
      preference for the septum. This suggests that cell wall synthesis is not
      dispersed but occurs at specific places along the lateral cell wall. The results
      implicate PBP3, PBP5 and PBP4a, and possibly PBP4, in lateral wall growth.
      Localization of PBPs to the septum was found to be dependent on FtsZ, but the GFP
      PBP fluorescence patterns were not detectably altered in the absence of MreB or
      Mbl.

PMID- 14731277
TI  - Site-directed mutagenesis of a LuxR-type quorum-sensing transcription factor:
      alteration of autoinducer specificity.
AB  - TraR is a quorum-sensing transcription factor from Agrobacterium tumefaciens that
      regulates replication and conjugation genes of the tumour-inducing (Ti) plasmid.
      TraR activity requires the autoinducer pheromone N-3-oxooctanoyl-l-homoserine
      lactone (OOHL). Structural studies of TraR-OOHL-DNA complexes showed that one
      molecule of OOHL is completely engulfed within the N-terminal domain of each TraR
      subunit. TraR is thought to bind OOHL via four hydrogen bonds, three of them
      direct and one water mediated, and by numerous hydrophobic interactions. Here, we
      show that all residues predicted to hydrogen bond with OOHL are essential for
      wild-type protein function. Mutants that failed to detect OOHL in vivo invariably
      failed to sequester exogenous OOHL. We showed previously that TraR is protected
      from cellular proteases by OOHL, and now show that mutants that failed to detect
      OOHL were also not protected from proteolysis by OOHL. We also describe several
      mutants with altered autoinducer specificity. Three mutants (T129V, T129A and
      T115I) detected 3-oxo-AHLs and 3-unsubstituted AHLs with equal sensitivity,
      indicating that these mutations perturb the water-mediated hydrogen bond to the 3
      oxo moiety of OOHL. Three other mutants (A49I, A49M and Q58L) preferentially
      detected AHLs containing six or seven carbon atoms rather than eight. The bulkier
      residues in these mutations appear to have occupied a portion of the OOHL binding
      site, interfering with binding of the acyl chain of AHLs.

PMID- 14731279
TI  - A novel biotin protein required for reductive carboxylation of 2-oxoglutarate by
      isocitrate dehydrogenase in Hydrogenobacter thermophilus TK-6.
AB  - Isocitrate dehydrogenase was purified from Hydrogenobacter thermophilus, and the
      corresponding gene was cloned and sequenced. The enzyme had similar structural
      properties to the isocitrate dehydrogenase of Escherichia coli, but differed in
      its catalytic properties, such as coenzyme specificity, pH dependency and kinetic
      parameters. Notably, the enzyme catalysed the oxidative decarboxylation of
      isocitrate, but not the reductive carboxylation of 2-oxoglutarate. The
      carboxylation reaction required the addition of cell extract and ATP-Mg,
      suggesting the existence of additional carboxylation factor(s). Further analysis
      of the carboxylation factor(s) resulted in the purification of two polypeptides.
      N-terminal amino acid sequencing revealed that the two polypeptides are
      homologues of pyruvate carboxylase with a biotinylated subunit, but do not
      catalyse pyruvate carboxylation. Pyruvate carboxylase was also purified, but was
      not active in stimulating isocitrate dehydrogenase. Isocitrate dehydrogenase, the
      novel biotin protein, ATP-Mg and NADH were essential for the reductive
      carboxylation of 2-oxoglutarate. These observations indicate that the novel
      biotin protein is an ATP-dependent factor, which is involved in the reverse
      (carboxylating) reaction of isocitrate dehydrogenase.

PMID- 14731278
TI  - The RNA degradosome and poly(A) polymerase of Escherichia coli are required in
      vivo for the degradation of small mRNA decay intermediates containing REP
      stabilizers.
AB  - In Escherichia coli, REP-stabilizers are structural elements in polycistronic
      messages that protect 5'-proximal cistrons from 3'-->5' exonucleolytic
      degradation. The stabilization of a protected cistron can be an important
      determinant in the level of gene expression. Our results suggest that RNase E, an
      endoribonuclease, initiates the degradation of REP-stabilized mRNA. However,
      subsequent degradation of mRNA fragments containing a REP-stabilizer poses a
      special challenge to the mRNA degradation machinery. Two enzymes, the DEAD-box
      RNA helicase, RhlB and poly(A) polymerase (PAP) are required to facilitate the
      degradation of REP-stabilizers by polynucleotide phosphorylase (PNPase). This is
      the first in vivo evidence that these enzymes are required for the degradation of
      REP-stabilizers. Furthermore, our results show that REP degradation by RhlB and
      PNPase requires their association with RNase E as components of the RNA
      degradosome, thus providing the first in vivo evidence that this ribonucleolytic
      multienzyme complex is involved in the degradation of structured mRNA fragments.

PMID- 14731280
TI  - Multiple stress signal integration in the regulation of the complex sigma S
      dependent csiD-ygaF-gabDTP operon in Escherichia coli.
AB  - The csiD-ygaF-gabDTP region in the Escherichia coli genome represents a cluster
      of sigma S-controlled genes. Here, we investigated promoter structures, sigma
      factor dependencies, potential co-regulation and environmental regulatory
      patterns for all of these genes. We find that this region constitutes a complex
      operon with expression being controlled by three differentially regulated
      promoters: (i) csiDp, which affects the expression of all five genes, is cAMP
      CRP/sigma S-dependent and activated exclusively upon carbon starvation and
      stationary phase; (ii) gabDp1, which is sigma S-dependent and exhibits multiple
      stress induction like sigma S itself; and (iii) gabDp2[previously suggested by
      Schneider, B.L., Ruback, S., Kiupakis, A.K., Kasbarian, H., Pybus, C., and
      Reitzer, L. (2002) J. Bacteriol. 184: 6976-6986], which appears to be Nac/sigma
      70-controlled and to respond to poor nitrogen sources. In addition, we identify a
      novel repressor, CsiR, which modulates csiDp activity in a temporal manner during
      early stationary phase. Finally, we propose a physiological role for sigma S
      controlled GabT/D-mediated gamma-aminobutyrate (GABA) catabolism and glutamate
      accumulation in general stress adaptation. This physiological role is reflected
      by the activation of the operon-internal gabDp1 promoter under the different
      conditions that also induce sigma S, which include shifts to acidic pH or high
      osmolarity as well as starvation or stationary phase.

PMID- 14731281
TI  - Application of AgaR repressor and dominant repressor variants for verification of
      a gene cluster involved in N-acetylgalactosamine metabolism in Escherichia coli K
      12.
AB  - The agaZVWEFASYBCDI gene cluster encodes the phosphotransferase systems and
      enzymes responsible for the uptake and metabolism of N-acetylgalactosamine and
      galactosamine in Escherichia coli. In some strains of E. coli, particularly the
      common K-12 strain, a portion of this cluster is missing because of a site
      specific recombination event that occurred between sites in agaW and agaA.
      Strains that have undergone this recombination event have lost the ability to
      utilize either N-acetylgalactosamine or galactosamine as sole sources of carbon.
      Divergently transcribed from this gene cluster is the gene agaR encoding a
      transcriptional repressor belonging to the DeoR/GlpR family of transcriptional
      regulators. Promoters upstream of agaR, agaZ and agaS were characterized. All
      three promoters had elevated activity in the presence of N-acetylgalactosamine or
      galactosamine, were regulated in vivo by AgaR and possessed specific DNA-binding
      sites for AgaR upstream from the start sites of transcription as determined by
      DNase I footprinting. In vivo analysis and DNase I footprinting indicated that
      the promoter specific for agaZ also requires activation by cAMP-CRP. Previous
      work with GlpR and other members of the DeoR/GlpR family have identified highly
      conserved amino acid residues that function in DNA-binding or response to
      inducer. These residues of AgaR were targeted for site-directed mutagenesis and
      yielded variants of AgaR that were either negatively dominant or non-inducible.
      The apparent ability to produce negatively dominant and non-inducible variants of
      proteins of the DeoR/GlpR family of currently unknown function will likely
      facilitate screening for function.

PMID- 14731282
TI  - Initiation of intracellular offspring in Epulopiscium.
AB  - Epulopiscium spp. are the largest heterotrophic bacteria yet described. A
      distinguishing feature of the Epulopiscium group is their viviparous production
      of multiple, internal offspring as a means of cellular reproduction. Based on
      their phylogenetic position, among low G + C Gram-positive endospore-forming
      bacteria, and the remarkable morphological similarity between developing
      endospores and Epulopiscium offspring, we hypothesized that intracellular
      offspring production in Epulopiscium evolved from endospore formation. These
      observations also raise the possibility that a cell with the capacity to form
      multiple intracellular offspring was the ancestor of all contemporary endospore
      forming bacteria. In an effort to characterize mechanisms common to both
      processes, we describe the earliest stages of offspring formation in
      Epulopiscium. First, in anticipation of polar division, some of the mother cell
      DNA coalesces at the cell poles. FtsZ then localizes in a bipolar pattern and the
      cell divides. A portion of the pole-associated DNA is trapped within the small
      cells formed by division at both poles. As development progresses, more pole
      associated DNA is apparently packaged into the offspring primordia. These results
      illustrate three mechanisms, the reorganization of cellular DNA, asymmetric
      division and DNA packaging, that are common to both endospore formation in
      Bacillus subtilis and the production of active, intracellular offspring in
      Epulopiscium. Unlike most endospore formers, Epulopiscium partitions only a small
      proportion of mother cell DNA into the developing offspring.

PMID- 14731283
TI  - A novel integrative and conjugative element (ICE) of Escherichia coli: the
      putative progenitor of the Yersinia high-pathogenicity island.
AB  - Diversification of bacterial species and pathotypes is largely caused by
      horizontal transfer of diverse DNA elements such as plasmids, phages and genomic
      islands (e.g. pathogenicity islands, PAIs). A PAI called high-pathogenicity
      island (HPI) carrying genes involved in siderophore-mediated iron acquisition
      (yersiniabactin system) has previously been identified in Yersinia pestis, Y.
      pseudotuberculosis and Y. enterocolitica IB strains, and has been characterized
      as an essential virulence factor in these species. Strikingly, an orthologous HPI
      is a widely distributed virulence determinant among Escherichia coli and other
      Enterobacteriaceae which cause extraintestinal infections. Here we report on the
      HPI of E. coli strain ECOR31 which is distinct from all other HPIs described to
      date because the ECOR31 HPI comprises an additional 35 kb fragment at the right
      border compared to the HPI of other E. coli and Yersinia species. This part
      encodes for both a functional mating pair formation system and a DNA-processing
      region related to plasmid CloDF13 of Enterobacter cloacae. Upon induction of the
      P4-like integrase, the entire HPI of ECOR31 is precisely excised and
      circularised. The HPI of ECOR31 presented here resembles integrative and
      conjugative elements termed ICE. It may represent the progenitor of the HPI found
      in Y. pestis and E. coli, revealing a missing link in the horizontal transfer of
      an element that contributes to microbial pathogenicity upon acquisition.

PMID- 14731284
TI  - Escherichia coli Hsp31 functions as a holding chaperone that cooperates with the
      DnaK-DnaJ-GrpE system in the management of protein misfolding under severe stress
      conditions.
AB  - Escherichia coli Hsp31 is a homodimeric protein that exhibits chaperone activity
      in vitro and is a representative member of a recently recognized family of heat
      shock proteins (Hsps). To gain insights on Hsp31 cellular function, we deleted
      the hchA gene from the MC4100 chromosome and combined the resulting null allele
      with lesions in other cytoplasmic chaperones. Although the hchA mutant only
      exhibited growth defects when cultivated at 48 degrees C, loss of Hsp31 had a
      strong deleterious effect on the ability of cells to survive and recover from
      transient exposure to 50 degrees C, and led to the enhanced aggregation of a
      subset of host proteins at this temperature. The absence of Hsp31 did not
      significantly affect the ability of the ClpB-DnaK-DnaJ-GrpE system to clear
      thermally aggregated proteins at 30 degrees C suggesting that Hsp31 does not
      possess disaggregase activity. Although it had no effect on the growth of
      groES30, Delta clpB or Delta ibpAB cells at high temperatures, the hchA deletion
      aggravated the temperature sensitive phenotype of dnaK756 and grpE280 mutants and
      led to increased aggregation in stressed dnaK756 cells. On the basis of
      biochemical, structural and genetic data, we propose that Hsp31 acts as a
      modified holding chaperone that captures early unfolding intermediates under
      prolonged conditions of severe stress and releases them when cells return to
      physiological conditions. This additional line of defence would complement the
      roles of DnaK-DnaJ-GrpE, ClpB and IbpB in the management of thermally induced
      cellular protein misfolding.

PMID- 14731285
TI  - A HU-like gene mutation in Rhizobium leguminosarum bv. viciae affects the
      expression of nodulation genes.
AB  - NodD is the major regulator of nod genes expression in rhizobia. Previously, a HU
      like protein in Rhizobium leguminosarum bv. viciae has been identified to bind
      specifically with nod promoters and be involved in in vitro nodD transcription,
      but its in vivo function remained unknown. In this work we have cloned and
      sequenced the R. leguminosarum bv. viciae gene, named hurL, for this HU-like
      protein. Using the E. coli-expressed HurL proteins, we proved that HurL had high
      affinity to several nod promoters and showed a stimulation effect on in vitro
      nodD transcription at appropriate concentration. The R. leguminosarum bv. viciae
      hurL gene was mutated by insertion of a kanamycin resistance cassette. The
      obtained hurL mutant strain M704 exhibited poor growth under free-living
      conditions and failed to induce nodules on Pisum sativum cv. Frisson and Vicia
      hirsuta. Further studies of NodD production and nod genes-lacZ fusions expression
      in the hurL mutant revealed that inactivation of hurL led to severe impairment in
      the nodD expression, repression in the inducible expression of nodA and nodF, and
      slight enhancement in the expression of px2, a gene identified earlier in this
      lab. These results suggested that hurL might be required for maintaining the
      normal expression of nod genes in R. leguminosarum bv. viciae.

PMID- 14731286
TI  - Deletion analyses of the peptidoglycan-associated lipoprotein Pal reveals three
      independent binding sequences including a TolA box.
AB  - The Tol-Pal system of the Escherichia coli cell envelope is composed of five
      proteins. TolQ, TolR and TolA form a complex in the inner membrane, whereas TolB
      is a periplasmic protein interacting with Pal, the peptidoglycan-associated
      lipoprotein anchored to the outer membrane. This system is required for outer
      membrane integrity and has been shown to form a trans-envelope bridge linking
      inner and outer membranes. The TolA-Pal interaction plays an important role in
      the function of this system and has been found to depend on the proton motive
      force and the TolQ and TolR proteins. The Pal lipoprotein interacts with many
      components, such as TolA, TolB, OmpA, the major lipoprotein and the murein layer.
      In this study, six pal deletions were constructed. The analyses of the resulting
      Pal protein functions and interactions defined an N-terminal region of 40
      residues, which can be deleted without any cell-damaging effect, and three
      independent regions required for its interaction with TolA, OmpA and TolB or the
      peptidoglycan. The analyses of the integrity of the cells producing the various
      Pal lipoproteins revealed strong outer membrane destabilization only when binding
      regions were deleted. Furthermore, a conserved polypeptide sequence located
      downstream of the peptidoglycan binding motif of Pal was required for the TolA
      Pal interaction and for the maintenance of outer membrane stability.

PMID- 14731287
TI  - A search for amino acid substitutions that universally activate response
      regulators.
AB  - Two-component regulatory systems, typically composed of a sensor kinase to detect
      a stimulus and a response regulator to execute a response, are widely used by
      microorganisms for signal transduction. Response regulators exhibit a high degree
      of structural similarity and undergo analogous activating conformational changes
      upon phosphorylation. The activity of particular response regulators can be
      increased by specific amino acid substitutions, which either prolong the lifetime
      or mimic key features of the phosphorylated state. We probed the universality of
      response regulator activation by amino acid substitution. Thirty-six mutations
      that activate 11 different response regulators were identified from the
      literature. To determine whether the activated phenotypes would be retained in
      the context of a different response regulator, we recreated 51 analogous amino
      acid substitutions at corresponding positions of CheY. About 55% of the tested
      substitutions completely or partially inactivated CheY, approximately 30% were
      phenotypically silent, and approximately 15% activated CheY. Three previously
      uncharacterized activated CheY mutants were found. The 94NS (and presumably 94NT)
      substitutions resulted in resistance to CheZ-mediated dephosphorylation. The
      113AP substitution led to enhanced autophosphorylation and may increase the
      fraction of non-phosphorylated CheY molecules that populate the activated
      conformation. The locations of activating substitutions on the response regulator
      three-dimensional structure are generally consistent with current understanding
      of the activation mechanism. The best candidates for potentially universal
      activating substitutions of response regulators identified in this study were
      13DK and 113AP.

PMID- 14731288
TI  - A bacterial cell-cell communication signal with cross-kingdom structural
      analogues.
AB  - Extracellular signals are the key components of microbial cell-cell communication
      systems. This report identified a diffusible signal factor (DSF), which regulates
      virulence in Xanthomonas campestris pv. campestris, as cis-11-methyl-2-dodecenoic
      acid, an alpha,beta unsaturated fatty acid. Analysis of DSF derivatives
      established the double bond at the alpha,beta positions as the most important
      structural feature for DSF biological activity. A range of bacterial pathogens,
      including several Mycobacterium species, also displayed DSF-like activity.
      Furthermore, DSF is structurally and functionally related to farnesoic acid (FA),
      which regulates morphological transition and virulence by Candida albicans, a
      fungal pathogen. Similar to FA, which is also an alpha,beta unsaturated fatty
      acid, DSF inhibits the dimorphic transition of C. albicans at a physiologically
      relevant concentration. We conclude that alpha,beta unsaturated fatty acids
      represent a new class of extracellular signals for bacterial and fungal cell-cell
      communications. As prokaryote-eukaryote interactions are ubiquitous, such cross
      kingdom conservation in cell-cell communication systems might have significant
      ecological and economic importance.

PMID- 14731289
TI  - Confocal laser scanning microscopy - an attractive tool for studying the uptake
      of xenobiotics into plant foliage.
AB  - The application of confocal laser scanning microscopy (CLSM) to the study of
      xenobiotic uptake into plant foliage is explored in this paper. Three fluorescent
      dyes of low molecular weight and contrasting polarities (hydrophilic, moderately
      lipophilic and lipophilic) were selected to represent foliage-applied pesticides.
      These model compounds were applied as droplets to the surfaces of various leaves
      and/or fruits according to the particular experiment. The transcuticular
      diffusion behaviour, the compartmentation into epidermal cells and the influence
      of a surfactant on the uptake of these fluorescent compounds were visualized by
      CLSM. Distinct differences in diffusion speed across the cuticle and distribution
      in cell compartments were found between different fluorescent compounds. The
      presence of a surfactant significantly accelerated the uptake of the moderately
      lipophilic dye into both thin- and thick-cuticled leaves. The results are
      discussed in relation to the current knowledge on pesticide uptake and
      translocation. The advantages and limitations of this technique are highlighted.

PMID- 14731290
TI  - Analysis of networks based on styrene and divinylbenzene containing iron anchored
      using variable pressure scanning electron microscopy.
AB  - There is great demand for the development of composite materials containing small
      metal or metal oxides particles, owing to their variable properties and wide
      application. However, microscopic evaluation of these materials using high-vacuum
      scanning electron microscopy is difficult because the samples must undergo a
      series of preparation steps to reach a high image quality and to avoid becoming
      shrunk inside the microscope vacuum chamber. Thus, in this study, we used
      variable pressure scanning electron microscopy to evaluate the morphology and
      iron distribution on the surface of magnetic microspheres based on poly(styrene
      co-divinylbenzene). These materials were obtained by suspension copolymerization
      of styrene and divinylbenzene in the presence of fine iron particles. Energy
      dispersive X-rays were also used to analyse distribution of the iron particles.
      The results indicate that, under the conditions used, magnetic microspheres with
      a relatively narrow size distribution were formed. Moreover, the micrographs show
      that agglomerated iron particles appeared only on the microsphere surface.

PMID- 14731291
TI  - Fluorescence microscopy of colour-tagged nanoparticles that are undergoing
      thermal motion.
AB  - To bypass limitations of conventional biochemical analysis, single-particle
      biochemical analysis is used. To improve single-particle biochemical analysis,
      procedures are needed to keep nanometre-sized particles in focus while the
      particles are undergoing thermal motion. A simple, inexpensive procedure is
      developed here for keeping particles in focus during the continuous
      observing/discriminating/recording of two different particles, both of which are
      undergoing thermal motion. This procedure concentrates the particles in a plane
      of solution that is in focus when the cover glass surface is in focus. An
      essential component of the procedure is the addition of molten, low-melt agarose
      to the specimen. Motionless binding to glass is inhibited by inclusion of anti
      stick additives in the specimen. Both carrier protein (gelatin) and non-ionic
      detergent (Triton X-100) are anti-stick additives successfully used here. Intact
      bacteriophages T3 and T7 are used as model particles, in anticipation of the use
      of the procedures developed here for the analysis of the assembly of
      bacteriophages. Observing/discriminating/recording of colour-tagged
      bacteriophages T3 and T7 is achieved at video frame rate with image splitting to
      discriminate colours.

PMID- 14731292
TI  - Picosecond time-resolved microspectrofluorometry in live cells exemplified by
      complex fluorescence dynamics of popular probes ethidium and cyan fluorescent
      protein.
AB  - Time-resolved microspectrofluorometry in live cells, based on time- and space
      correlated single-photon counting, is a novel method to acquire spectrally
      resolved fluorescence decays, simultaneously in 256 wavelength channels. The
      system is calibrated with a full width at half maximum (FWHM) of 90 ps for the
      temporal resolution, a signal-to-noise ratio of 10(6), and a spectral resolution
      of 30 (Deltalambda/Lambda). As an example, complex fluorescence dynamics of
      ethidium and cyan fluorescent protein (CFP) in live cells are presented. Free and
      DNA intercalated forms of ethidium are simultaneously distinguishable by their
      relative lifetime (1.7 ns and 21.6 ns) and intensity spectra (shift of 7 nm). By
      analysing the complicated spectrally resolved fluorescence decay of CFP, we
      propose a fluorescence kinetics model for its excitation/desexcitation process.
      Such detailed studies under the microscope and in live cells are very promising
      for fluorescence signal quantification.

PMID- 14731293
TI  - Correlation-based methods of automatic particle detection in electron microscopy
      images with smoothing by anisotropic diffusion.
AB  - Two methods of correlation-based automatic particle detection in electron
      microscopy images are compared - computing a cross-correlation function or a
      local correlation coefficient vs. azimuthally averaged reference projections
      (either from a model or from experimental particle images). The ability of
      smoothing images by anisotropic diffusion to improve the performance of particle
      detection is also considered. Anisotropic diffusion is an effective method of
      preprocessing that enhances the edges and overall shape of particles while
      reducing noise. It is found that anisotropic diffusion improves particle
      detection by a local correlation coefficient when projections from a high
      resolution reconstruction are used as references. When references from
      experimental particle images are used, a cross-correlation function shows a more
      marked improvement in particle detection in images smoothed by anisotropic
      diffusion.

PMID- 14731294
TI  - Progress in near-field photothermal infra-red microspectroscopy.
AB  - Near-field photothermal Fourier transform infra-red microspectroscopy, which
      utilizes atomic force microscopy (AFM)-type temperature sensors, is being
      developed with the aim of achieving a spatial resolution higher than the
      diffraction limit. Here we report on a new implementation of the technique.
      Sensitivity of the technique is assessed by recording infra-red spectra from
      small quantities of analytes and thin films. A photothermomechanical approach,
      which utilizes conventional AFM probes as temperature sensors, is also discussed
      based on preliminary results. Early indication suggests that the photothermal
      approach is more sensitive than the thermomechanical one.

PMID- 14731295
TI  - Near-field optical microscope observation of dye-containing nano-domains.
AB  - A novel method for forming dye-containing nano-domains in thin films using a
      polymer alloy system has been developed. The polymer alloy system (PS-b-PMMA),
      which consists of polystyrene (PS) and polymethyl methacrylate (PMMA), forms
      microphase separation in thin films. The film was treated using a previously
      reported technique under vacuum conditions, and an organic dye was selectively
      dispersed into the PS. Selective association of the dye (diarylethene; cis-1, 2
      dicyano-1, 2-bis (2,4,5-trimethyl-3-thienyl) ethene) with the PS nano-domains was
      then observed, with both transmission electron microscopy and scanning near-field
      optical microscopy with an absorption spectrum.

PMID- 14731296
TI  - A new structure for enhanced transmission through a two-dimensional metallic
      grating.
AB  - The spectral response of metallic two-dimensional periodic structures in which
      circular apertures are engraved has been extensively studied. We show that in
      such devices transmission can be highly enhanced by partially shutting the
      central parts of each aperture in order to make a periodic array of subwavelength
      coaxial structures.

PMID- 14731297
TI  - Waveguiding through a two-dimensional metallic photonic crystal.
AB  - We present a two-dimensional (2D) finite-difference time domain simulation of the
      propagation of light through linear and bent channels in metallic photonic
      crystals. We took as a starting point the Bozhevolnyi experiment, consisting of
      the scattering of surface plasmons by a 2D structure of finitely sized periodic
      gold dots arranged in a triangular lattice of 400-nm period. We model injection
      and propagation of light through linear channels of different widths. We also
      study the behaviour of light in the presence of a 90 degrees bent line defect
      made in the structure. We show that the confinement depends on the orientation of
      the input and output line defects. The two cases of GammaM and GammaK
      orientations are considered and a spectral study for five different wavelengths
      is carried out.

PMID- 14731298
TI  - Laser scanning confocal microscopy for in situ monitoring of alkali-silica
      reaction.
AB  - Alkali-silica reaction (ASR) occurs in concrete between reactive siliceous
      components in the aggregate and the strongly alkaline pore solution, resulting in
      the formation of a potentially expansive gel product. Lithium additives have been
      shown to reduce expansion associated with ASR, but the mechanism(s) by which
      lithium reduces expansion have not been understood. Therefore, development of an
      in situ method to observe reactions associated with ASR is highly desirable, as
      it will allow for non-destructive observation of the reaction product formation
      and damage evolution over time, as the reaction progresses. A technique to image
      into mortar through glass aggregate by laser scanning confocal microscopy (LSCM),
      producing three-dimensional representations of the sample was developed. This
      LSCM technique was utilized to monitor the progress of alkali-silica reaction in
      mortar samples prepared with alkali-reactive glass aggregate both in the presence
      and in the absence of lithium additives: LiNO3, LiCl or LiOH. The method proved
      to be effective in qualitatively monitoring crack formation and growth and
      product formation, within cracks and at the paste/aggregate interface. In
      particular, dendritic products were observed at the paste/aggregate interface
      only in those samples containing lithium, suggesting that these products may play
      a role in ASR mitigation.

PMID- 14731299
TI  - Quantification and visualization of anisotropy in trabecular bone.
AB  - A number of methods for measuring anisotropy in trabecular bone using high
      resolution X-ray computed tomography exist, which give different answers but have
      not been compared in detail. In this study, we examine the mean-intercept length
      (MIL), star volume distribution (SVD) and star length distribution (SLD) methods,
      their algorithmic implementation for three-dimensional (3D) data, and how their
      results relate to each other. A uniform ordered sampling scheme for determining
      which orientations to sample during analysis enhances the reproducibility of
      anisotropy and principal component direction determinations, with no evident
      introduction of biasing. This scheme also facilitates the creation of a 3D rose
      diagram that can be used to gain additional insights from the data. The directed
      secant algorithm that is frequently used for traversing pixel and voxel grids for
      these calculations is prone to bias unless a previously unreported normalization
      is used. This normalization ameliorates the bias present when using cubic voxels,
      and also permits calculations on data sets in which the slice spacing is not
      equal to the pixel spacing. Overall, the three methods for quantification of
      anisotropy give broadly similar results, but there are systematic divergences
      that can be traced to their differences in data and processing, and which may
      impact on their relative utility in estimating mechanical properties. Although
      discussed in the context of computed tomography of trabecular bone, the methods
      described here may be applied to any 3D data set from which fabric information is
      desired.

PMID- 14731300
TI  - Terminal protein-induced stretching of bacteriophage phi29 DNA.
AB  - Stretching of DNA molecules helps to resolve detail during the fluorescence
      microscopy of both single DNA molecules and single DNA-protein complexes. To make
      stretching occur, intricate procedures of specimen preparation and manipulation
      have been developed in previous studies. By contrast, the present study
      demonstrates that conventional procedures of specimen preparation cause DNA
      stretching to occur, if the specimen is the double-stranded DNA genome of
      bacteriophage phi29. Necessary for this stretching is a protein covalently bound
      at both 5' termini of phi29 DNA molecules. Some DNA molecules are attached to a
      cover glass only at the two ends. Others are attached at one end only with the
      other end free in solution. The extent of stretching varies from approximately
      50% overstretched to approximately 50% understretched. The understretched DNA
      molecules are internally mobile to a variable extent. In addition to stretching,
      some phi29 DNA molecules also undergo assembly to form both linear and branched
      concatemers observed by single-molecule fluorescence microscopy. The assembly
      also requires the terminal protein. The stretched DNA molecules are potentially
      useful for observing DNA biochemistry at the single molecule level.

PMID- 14731301
TI  - Magnetosomal matrix: ultrafine structure may template biomineralization of
      magnetosomes.
AB  - The organic matrix surrounding bullet-shaped, cubo-octahedral, D-shaped,
      irregular arrowhead-shaped, and truncated hexa-octahedral magnetosomes was
      analysed in a variety of uncultured magnetotactic bacteria. The matrix was
      examined using low- (80 kV) and intermediate- (400 kV) voltage TEM. It
      encapsulated magnetosomes in dehydrated cells, ultraviolet-B-irradiated
      dehydrated cells and stained resin-embedded fixed cells, so the apparent
      structure of the matrix does not appear to be an artefact of specimen
      preparation. High-resolution images revealed lattice fringes in the matrix
      surrounding magnetite and greigite magnetosomes that were aligned with lattice
      fringes in the encapsulated magnetosomes. In all except one case, the lattice
      fringes had widths equal to or twice the width of the corresponding lattice
      fringes in the magnetosomes. The lattice fringes in the matrix were aligned with
      the [311], [220], [331], [111] and [391] related lattice planes of magnetite and
      the [222] lattice plane of greigite. An unidentified material, possibly an iron
      hydroxide, was detected in two immature magnetosomes containing magnetite. The
      unidentified phase had a structure similar to that of the matrix as it contained
      [311], [220] and [111] lattice fringes, which indicates that the matrix acts as a
      template for the spatially controlled biomineralization of the unidentified
      phase, which itself transforms into magnetite. The unidentified phase was thus
      called pre-magnetite. The presence of the magnetosomal matrix explains all of the
      five properties of the biosignature of the magnetosomal chain proposed previously
      by Friedmann et al. and supports their claim that some of the magnetite particles
      in the carbonate globules in the Martian meteorite ALH84001 are biogenic. Two new
      morphologies of magnetite magnetosomes are also reported here (i.e. tooth-shaped
      and hexa-octahedral magnetosomes). Tooth-shaped magnetite magnetosomes elongated
      in the [110] direction are reported, and are distinct from arrowhead-shaped and
      bullet-shaped magnetosomes. Elongation of magnetite magnetosomes in the [110]
      direction has not been reported previously. A Martian hexa-octahedral magnetite
      particle was previously characterized by Thomas-Keptra et al. and compared with
      truncated hexa-octahedral magnetite magnetosomes. Hexa-octahedral magnetite
      magnetosomes with the same morphology and similar sizes and axial ratios as those
      reported by Thomas-Keptra et al. are characterized here. These observations
      support their claim that ALH84001 contains evidence for a past Martian biota.

PMID- 14731302
TI  - Static and dynamic experiments in cryo-electron microscopy: comparative
      observations using high-vacuum, low-voltage and low-vacuum SEM.
AB  - We carried out a unique comparative study between three modes of cryo-scanning
      electron imaging: high-vacuum, low-voltage and low-vacuum, using ice cream as a
      model system. Specimens were investigated both with and without a conductive
      coating (Au/Pd) and at temperatures for which ice either remains fully frozen (< 
      110 degrees C) or undergoes sublimation (-110 to -90 degrees C). At high
      magnification, high-vacuum imaging of coated specimens gave the best results for
      'static' specimens (i.e. containing fully frozen ice). Low voltages, such as 1
      kV, could be used for imaging uncoated specimens at high vacuum, although slight
      'classical' charging artefacts remained an issue, and the reduced electron beam
      penetration tended to decrease the definition between different microstructural
      features. However, this mode was useful for observing in situ sublimation from
      uncoated specimens. Low-vacuum mode, involving small partial pressures of
      nitrogen gas, was particularly suited to in situ sublimation work: when
      sublimation was carried out in low vacuum in the absence of an anti-contaminator
      plate, sublimation rates were significantly reduced. This is attributed to a
      small partial pressure of sublimated water vapour remaining near the specimen
      surface, enhancing thermodynamic stability.

PMID- 14731303
TI  - Precision of the fractionator from Cavalieri designs.
AB  - A popular procedure to predict the variance of the fractionator consists in
      splitting the initial collection of fragments into two subsets, in order to use
      the corresponding particle counts (or any other pertinent measure), in the
      calculation. The current formula does not account for local or 'nugget' errors
      inherent in the estimation of fragment contents, however. Moreover, it does not
      account for the fact that the contribution of the variability between fragments
      or slices should rapidly decrease as the sampling fraction increases. For these
      reasons, an update to the formula is overdue. It should be stressed, however,
      that the formula applies to Cavalieri slices designs - its application for
      arbitrary partition designs is therefore not warranted.

PMID- 14731304
TI  - The colonization of land by animals: molecular phylogeny and divergence times
      among arthropods.
AB  - BACKGROUND: The earliest fossil evidence of terrestrial animal activity is from
      the Ordovician, approximately 450 million years ago (Ma). However, there are
      earlier animal fossils, and most molecular clocks suggest a deep origin of animal
      phyla in the Precambrian, leaving open the possibility that animals colonized
      land much earlier than the Ordovician. To further investigate the time of
      colonization of land by animals, we sequenced two nuclear genes, glyceraldehyde-3
      phosphate dehydrogenase and enolase, in representative arthropods and conducted
      phylogenetic and molecular clock analyses of those and other available DNA and
      protein sequence data. To assess the robustness of animal molecular clocks, we
      estimated the deuterostome-arthropod divergence using the arthropod fossil record
      for calibration and tunicate instead of vertebrate sequences to represent
      Deuterostomia. Nine nuclear and 15 mitochondrial genes were used in phylogenetic
      analyses and 61 genes were used in molecular clock analyses. RESULTS: Significant
      support was found for the unconventional pairing of myriapods (millipedes and
      centipedes) with chelicerates (spiders, scorpions, horseshoe crabs, etc.) using
      nuclear and mitochondrial genes. Our estimated time for the divergence of
      millipedes (Diplopoda) and centipedes (Chilopoda) was 442 +/- 50 Ma, and the
      divergence of insects and crustaceans was estimated as 666 +/- 58 Ma. Our results
      also agree with previous studies suggesting a deep divergence (approximately 1100
      - 900 Ma) for arthropods and deuterostomes, considerably predating the Cambrian
      Explosion seen in the animal fossil record. CONCLUSIONS: The consistent support
      for a close relationship between myriapods and chelicerates, using mitochondrial
      and nuclear genes and different methods of analysis, suggests that this
      unexpected result is not an artefact of analysis. We propose the name
      Myriochelata for this group of animals, which includes many that immobilize prey
      with venom. Our molecular clock analyses using arthropod fossil calibrations
      support earlier studies using vertebrate calibrations in finding that
      deuterostomes and arthropods diverged hundreds of millions of years before the
      Cambrian explosion. However, our molecular time estimate for the divergence of
      millipedes and centipedes is close to the divergence time inferred from fossils.
      This suggests that arthropods may have adapted to the terrestrial environment
      relatively late in their evolutionary history.

PMID- 14731305
TI  - Collagenolytic serine protease PC and trypsin PC from king crab Paralithodes
      camtschaticus: cDNA cloning and primary structure of the enzymes.
AB  - BACKGROUND: In this paper, we describe cDNA cloning of a new anionic trypsin and
      a collagenolytic serine protease from king crab Paralithodes camtschaticus and
      the elucidation of their primary structures. Constructing the phylogenetic tree
      of these enzymes was undertaken in order to prove the evolutionary relationship
      between them. RESULTS: The mature trypsin PC and collagenolytic protease PC
      contain 237 (Mcalc 24.8 kDa) and 226 amino acid residues (Mcalc 23.5 kDa),
      respectively. Alignments of their amino acid sequences revealed a high degree of
      the trypsin PC identity to the trypsin from Penaeus vannamei (approximately 70%)
      and of the collagenolytic protease PC identity to the collagenase from fiddler
      crab Uca pugilator (76%). The phylogenetic tree of these enzymes was constructed.
      CONCLUSIONS: Primary structures of the two mature enzymes from P. camtschaticus
      were obtained and compared with those of other proteolytic proteins, including
      some enzymes from brachyurans. A phylogenetic analysis was also carried out.
      These comparisons revealed that brachyurins are closely related to their
      vertebrate and bacterial congeners, occupy an intermediate position between them,
      and their study significantly contributes to the understanding of the evolution
      and function of serine proteases.

PMID- 14731306
TI  - Emergency department spirometric volume and base deficit delineate risk for torso
      injury in stable patients.
AB  - BACKGROUND: We sought to determine torso injury rates and sensitivities
      associated with fluid-positive abdominal ultrasound, metabolic acidosis
      (increased base deficit and lactate), and impaired pulmonary physiology
      (decreased spirometric volume and PaO2/FiO2). METHODS: Level I trauma center
      prospective pilot and post-pilot study (2000-2001) of stable patients. Increased
      base deficit was < 0.0 in ethanol-negative and < or = -3.0 in ethanol-positive
      patients. Increased lactate was > 2.5 mmol/L in ethanol-negative and > or = 3.0
      mmol/L in ethanol-positive patients. Decreased PaO2/FiO2 was < 350 and decreased
      spirometric volume was < 1.8 L. RESULTS: Of 215 patients, 66 (30.7%) had a torso
      injury (abdominal/pelvic injury n = 35 and/or thoracic injury n = 43). Glasgow
      Coma Scale score was 14.8 +/- 0.5 (13-15). Torso injury rates and sensitivities
      were: abdominal ultrasound negative and normal base deficit, lactate, PaO2/FiO2,
      and spirometric volume--0.0% & 0.0%; normal base deficit and normal spirometric
      volume--4.2% & 4.5%; chest/abdominal soft tissue injury--37.8% & 47.0%; increased
      lactate--39.7% & 47.0%; increased base deficit--41.3% & 75.8%; increased base
      deficit and/or decreased spirometric volume--43.8% & 95.5%; decreased PaO2/FiO2-
      48.9% & 33.3%; positive abdominal ultrasound--62.5% & 7.6%; decreased spirometric
      volume--73.4% & 71.2%; increased base deficit and decreased spirometric volume-
      82.9% & 51.5%. CONCLUSIONS: Trauma patients with normal base deficit and
      spirometric volume are unlikely to have a torso injury. Patients with increased
      base deficit or lactate, decreased spirometric volume, decreased PaO2/FiO2, or
      positive FAST have substantial risk for torso injury. Increased base deficit
      and/or decreased spirometric volume are highly sensitive for torso injury. Base
      deficit and spirometric volume values are readily available and increase or
      decrease the suspicion for torso injury.

PMID- 14731307
TI  - Hypothesis: could the signalling function of membrane microdomains involve a
      localized transition of lipids from liquid to solid state?
AB  - BACKGROUND: Over the past decade, it has become apparent that specialised
      membrane microdomains, commonly called rafts, where lipids like sphingolipids and
      cholesterol are arranged compactly in a liquid ordered phase are involved in cell
      signalling. HYPOTHESIS: The core of the hypothesis presented here is that resting
      cells may actively maintain their plasma membrane in liquid phase, corresponding
      to a metastable thermodynamic state. Following a physiological stimulus such as
      ligands binding to their membrane receptors, the tendency of membrane components
      to undergo a localised transition towards a gel state would increase, resulting
      in initial minute solid structures. These few membrane components having
      undergone a liquid to solid state transition, would then act as seeds for the
      specific recruitment of additional membrane components whose properties are
      compatible with the crystalline growth of these initial docks. Cells could
      therefore be using the propensity of lipids to assemble selectively to generate
      stable platforms of particular cellular components either for intra-cellular
      transport or for signal transduction. TESTING THE HYPOTHESIS: could presumably be
      done via biophysical approaches such as EPR spin labelling, X-ray diffraction or
      FRET coupled to direct microscopic observation of cells to which very localized
      stimuli would be delivered. IMPLICATIONS: Such a model of selective growth of
      membrane docks would provide an explanation for the existence of different types
      of microdomains, and for the fact that, depending on the state of the cells and
      on the procedures used to isolate them, membrane microdomains can vary greatly in
      their properties and composition. Ultimately, a thorough understanding of how and
      why lipid domains are assembled in biological membranes will be essential for
      many aspects of cell biology and medicine.

PMID- 14731308
TI  - Selective effects of simultaneous monoamine depletion on mood and emotional
      responsiveness.
AB  - Monoamines play a significant role in the regulation of mood and emotion. While
      the selective effects of serotonin and catecholamine depletion on mood have been
      described, the effects of simultaneous monoamine depletion on subjective measures
      of mood and emotional responsiveness are yet to be examined. The current study
      aimed to investigate the effects of simultaneous monoamine depletion on mood and
      emotional responsiveness in healthy participants. Twenty female participants
      completed a randomized, double-blind, placebo-controlled study, under a balanced
      control condition (B), and a combined monoamine depletion condition (CMD; via
      tryptophan, tyrosine and phenylalanine depletion). Mood ratings Visual Analogue
      Mood Scale (VAMS) and Profile Of Mood States (POMS) and measures of emotional
      responsiveness (Emotional Stroop and International Affective Picture System) were
      examined at baseline and 5 h post-depletion. Following CMD, participants rated
      themselves as feeling sadder, more antagonistic, and mentally slower on three
      VAMS subscales. There were no significant mood changes found on the POMS or
      measures of emotional responsiveness. These findings suggest that simultaneous
      depletion of all monoamines may have selective effects on mood. The findings
      provide evidence that the simultaneous monoamine depletion technique may be a
      useful experimental method to probe central monoamine function in humans.

PMID- 14731309
TI  - A family-based association study of the 5-HT-1Dbeta receptor gene in obsessive
      compulsive disorder.
AB  - Pharmacological studies have shown that sumatriptan, a selective ligand of the
      serotonin 5-HT-1Dbeta autoreceptor, modifies obsessive-compulsive disorder (OCD)
      symptoms. The current study analysed the G861C polymorphism of the 5-HT-1Dbeta
      gene in a sample of 72 trios. Genotyping data were analysed using the Family
      Based Association Test (FBAT). We did not replicate the previously reported
      linkage disequilibrium between the G861 variant and OCD. However, a quantitative
      trait analysis, assessing severity of OCD symptoms and defined as YBOCS score,
      confirmed the finding that subjects with a preferential transmission of the G861
      variant showed higher YBOCS Obsession scores compared to patients carrying the
      C861 allele. These preliminary findings may indicate that the 5-HT-1Dbeta
      receptor gene could be involved in the severity of obsession symptoms in OCD.
      However, it is important to perform the replication of these findings in larger
      sample sizes of informative families.

PMID- 14731310
TI  - Augmentation of milnacipran by risperidone in treatment for major depression.
AB  - Milnacipran, one of the serotonin noradrenaline reuptake inhibitors (SNRIs) to
      which venlafaxine and duloxetine belong, is a new antidepressant that has
      recently become available in many countries. Despite the advances in
      pharmacotherapy, almost one third of patients with depressive illness respond
      inadequately to monotherapy with such an antidepressant. We herein describe five
      patients with major depression who responded partially, but not fully, to
      milnacipran alone and remarkably improved with an adjunct of risperidone. In
      addition, milnacipran plus risperidone was found to be a useful augmentation for
      treatment-refractory depression in 3 of the 5 patients. The minimum dose of
      risperidone, 0.5 or 1 mg/d, was efficacious. The time of response after addition
      of risperidone was within 4 d. Our experience suggests that an augmentation
      therapy of milnacipran plus risperidone is useful for treating patients with
      depression who only partially respond to various types of antidepressants and for
      treatment-refractory depression.

PMID- 14731311
TI  - Safety and efficacy of combined clozapine-lithium pharmacotherapy.
AB  - Several case reports described neurotoxic side-effects in the course of a
      combined clozapine-lithium treatment. Here we report on the safety and efficacy
      of this combination in a sample of 44 hospital patients. Medical records were
      retrospectively audited and a subsample of 23 patients was re-assessed. Mean
      total duration of combined treatment was 23.5 months. The combination
      (indications: prophylaxis; treatment of affective symptoms or
      aggression/excitement; augmentation of neuroleptic efficacy) was rated effective
      in 84% and adverse events were reported in 64% of the patients. Notably, most of
      the adverse events were benign and transient. However, 8 patients (18%) developed
      transient neurological adverse events that were genuinely novel in only 3
      patients (7%) and coincided with high dosage of medication or high plasma levels
      or serotonergic (antidepressant) co-medication. Our data suggest that combined
      clozapine-lithium treatment may appear to be safe and effective when administered
      within a moderate therapeutic dose range and without serotonergic co-medication
      or other substances interfering with clozapine metabolism.

PMID- 14731312
TI  - Acute augmentation of serotonin suppresses cardiovascular responses to emotional
      valence.
AB  - A key component in visceral reactivity to emotional states is heart rate (HR),
      however little is known about how HR response to emotional stimuli is modulated
      by neurochemicals. The present study investigated the way in which acute
      enhancement of serotonin (5-HT) function with a selective serotonin reuptake
      inhibitor (SSRI) modulates the HR associated with differently valent images
      (pleasant, neutral, unpleasant). Sixteen healthy participants viewed 75 images
      whilst HR was recorded. Participants were tested under two single-dose treatment
      conditions: placebo and citalopram (20 mg). Our findings suggest: (1) HR is able
      to differentiate differently valent images during placebo treatment and, (2)
      administration of citalopram suppresses the differences in HR between differently
      valent images. These results suggest that 5-HT may modulate the cardiovascular HR
      response to visual emotional stimuli and indicate that 5-HT may have a protective
      effect on the cardiovascular responses to emotional stimuli.

PMID- 14731313
TI  - A case of clarithromycin-induced manic episode (antibiomania).

PMID- 14731314
TI  - Neuroleptic malignant syndrome induced by donepezil.

PMID- 14731315
TI  - How to treat bipolar II depression and bipolar II mixed depression?

PMID- 14731317
TI  - Locally advanced, unresectable non-small cell lung cancer shift in the treatment
      paradigm.

PMID- 14731319
TI  - Phase III trial: concurrent chemotherapy and radiation therapy: a new standard of
      care for stage III non small-cell lung cancer?

PMID- 14731321
TI  - Lymph node micrometastases in non small-cell lung cancer: clinical applications.
AB  - A large number of patients are diagnosed every year with non small-cell lung
      cancer, and their prognosis and response to treatment are inversely correlated to
      tumor stage at initial diagnosis. Despite the surgical removal of all apparent
      malignancy from patients with early disease, many will relapse, presumably as a
      result of disease that was undetected at initial evaluation. In an effort to
      identify those patients who have early lymph node involvement by metastatic
      disease, several groups of investigators have searched for the presence of
      micrometastases in hematoxylin-eosin-negative lymph nodes using
      immunohistochemical or molecular methods. Four of six groups of investigators
      using immunohistochemistry have found a significant incidence of lymph node
      micrometastases and a direct correlation between the absence of micrometastases
      and disease-free survival; these are encouraging results that require
      confirmatory studies. Molecular methods may potentially offer increased
      sensitivity; however, their high cost and the requirement to process large
      numbers of samples limits their use to research settings at present.

PMID- 14731322
TI  - Vinorelbine and gemcitabine combinations in advanced non small-cell lung cancer.
AB  - Several new chemotherapeutic agents were developed and tested in advanced non
      small-cell lung cancer (NSCLC) in the past decade. Vinorelbine and gemcitabine
      showed consistent single-agent activity in phase II and III trials and have been
      shown to be superior to older combinations when combined with cisplatin. However,
      toxicity associated with these regimens remains substantial, and nonplatinum
      alternatives are currently being explored. Based on the individual activity of
      vinorelbine and gemcitabine, their distinct mechanisms of action, and their mild,
      nonoverlapping toxicities, several trials evaluated their use in combination in
      patients with advanced NSCLC. Therapy has been administered in a convenient
      outpatient setting over a period of 1 hour. Different weekly schedules have been
      tested, but in general, toxicity is mild and the regimen is well tolerated, even
      in elderly patients or those with a poor performance status. Efficacy seems to be
      at least comparable to traditional platinum-based regimens, with respect to
      overall response rate and survival. In summary, vinorelbine/gemcitabine is an
      active and well-tolerated regimen and represents an option for the treatment of
      patients with advanced NSCLC. Randomized studies comparing this combination to
      reference platinum- or taxane-based regimens are needed to further evaluate the
      role of this combination in advanced NSCLC.

PMID- 14731323
TI  - A phase I study of STEALTH cisplatin (SPI-77) and vinorelbine in patients with
      advanced non small-cell lung cancer.
AB  - STEALTH  cisplatin (SPI-77) is a liposomal formulation of cisplatin that has
      activity in animal models of non  small-cell lung cancer (NSCLC). Vinorelbine has
      documented clinical activity in NSCLC. The purpose of this study was to determine
      the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of SPI-77 when
      administered in combination with a fixed dose of vinorelbine to patients with
      stage IIIB or IV NSCLC refractory to or recurrent following previous
      chemotherapy. SPI-77 was given on day 1 in combination with vinorelbine at a
      fixed dose of 25 mg/m2 on days 1 and 8 of a 3-week treatment cycle. Dose
      escalation of SPI-77 progressed as follows: 20, 40, 80, 100, 120, and 140 mg/m2.
      Twenty patients were entered (11 men and nine women; median age, 63 years). Sixty
      four complete cycles of therapy were administered, and 19 of 20 patients
      completed at least 1 cycle of combination chemotherapy. Neutropenia was dose
      limiting at a SPI-77 dose of 140 mg/m2. Neuropathy and nephrotoxicity were
      minimal and not dose related. A partial response was observed in three of 17
      patients eligible for a response evaluation and response duration ranged from 6
      weeks to 5 months. In conclusion, treatment with combination SPI-77 and
      vinorelbine was well tolerated, and our recommended phase II dose is 120 mg/m2 of
      SPI-77 in combination with vinorelbine at 25 mg/m2. Activity was observed in this
      patient population, and additional phase II testing of this regimen in a less
      extensively pretreated cohort of patients with NSCLC is indicated.

PMID- 14731324
TI  - Second-line gemcitabine in refractory stage IV non small-cell lung cancer: a
      phase II trial.
AB  - Two recent trials have suggested that docetaxel improves survival in the second
      line treatment of non small-cell lung cancer (NSCLC) refractory to first-line
      platinum-based regimens. Given this, it is appropriate to continue to address the
      role of new agents in the second-line treatment of refractory NSCLC. Gemcitabine
      is a well-tolerated new agent that has been shown to have activity in NSCLC.
      Thirty-one previously treated patients with NSCLC were entered in this study.
      Eight patients had responsive disease (defined as response to first-line therapy
      lasting greater than or equal to 3 months) and 23 had refractory disease (defined
      as progressive disease on first-line therapy or progression less than 3 months
      from completing first-line therapy). Gemcitabine (1250 mg/m2) was infused over 30
      minutes on days 1, 8, and 15 every 28 days. Quality of life (QOL) was assessed
      with each cycle using the Functional Assessment Cancer Therapy-Lung (FACT-L)
      questionnaire. Two patients (6.5%) had a partial response, and nine (29%) had
      disease stabilization. The most frequent grade 3/4 toxicity was myelosuppression,
      but this only occurred in 8% of doses delivered. Fifty-two percent of evaluable
      patients had stable or improved QOL over baseline, 10% had a decline in QOL, and
      the remainder completed only baseline questionnaires. Twenty-nine patients have
      died of progressive NSCLC; two patients remain alive. Overall, the 31 patients
      have a median survival of 5.1 months (95% confidence interval [CI]: 4.2-7.4
      months) and 1-year survival rate of 16% (95% CI: 3%-29%). Gemcitabine was well
      tolerated in this patient population. An objective response rate of 6.5% was
      observed although a significant proportion of patients (29%) experienced stable
      disease, which may have impacted on their survival. QOL was improved or
      maintained in over half of the patients. Given these data, gemcitabine as a
      single agent is a therapeutic option for patients with refractory NSCLC.

PMID- 14731325
TI  - Fragile histidine triad (FHIT) gene abnormalities in lung cancer.
AB  - Lung cancer is the most common cause of cancer death in the world. In recent
      years, enormous progress has been made in understanding the molecular and
      cellular biology of lung cancer. The fragile histidine triad (FHIT) gene, a
      candidate tumor-suppressor gene, was recently identified at chromosome 3p14.2,
      spanning the FRA3B common fragile site. Frequent allelic losses as well as
      homozygous deletions have been described at the FHIT locus, making FHIT a strong
      candidate as a tumor-suppressor gene. However, the occurrence of mutations is
      very rare. Aberrant FHIT transcripts, including deletions of exons, insertions
      between exons, and insertions replacing exons, are detected in a high percentage
      of lung tumors. Reduction or complete loss of FHIT expression by
      immunohistochemical testing is seen in about 30%-70% of non small-cell lung
      cancer and in about 20% of bronchial biopsies from chronic smokers without
      evidence of lung cancer. This finding supports the theory that FHIT is a
      molecular target of tobacco smoke carcinogens. However, the location of the gene
      in one of the most fragile sites of the human genome and the paucity of mutations
      have led to an alternative hypothesis that abnormalities of the gene are
      bystander effects resulting from disruption of the FRA3B locus. Thus, the
      function of FHIT as a candidate tumor-suppressor gene is still controversial, and
      additional studies are necessary to clarify the role of FHIT in lung cancer
      pathogenesis.

PMID- 14731326
TI  - Treatment outcome of lung cancer patients as optimized by preoperative whole-body
      positron emission tomography fluorodeoxyglucose imaging.
AB  - Positron emission tomography (PET) fluorodeoxyglucose (FDG) imaging may be more
      accurate than computed tomography (CT) scanning for staging of lung cancer
      disease. In the present study, we evaluate whether whole-body PET-FDG imaging can
      accurately stratify lung cancer patients by stage and thus predict patient
      outcome. Forty-one consecutive patients underwent whole-body PET and CT scanning
      for preoperative staging, which was then confirmed by mediastinoscopy,
      thoracotomy, and/or other tests revealing distant metastases. The effect of PET
      on patient management was determined. PET was significantly more accurate than CT
      for staging of lung cancer (97.6% vs. 70.7%). One-year follow-up for survival
      rate and treatment response was also compared in different patient groups. PET
      accurately identified patients with resectable disease (Group A). Group B
      patients, with medically inoperable disease, and Group C patients, with
      unresectable advanced disease, had 100% and 53% incidence of adverse events
      (defined as recurrence, evidence of new disease, or death), respectively. Group A
      patients with resectable disease who underwent surgery showed the best patient
      outcome, with only 7% incidence of adverse events. In conclusion, whole-body PET
      can be useful in identifying a group of lung cancer patients with resectable
      disease most likely to benefit from surgical resection. Further studies are
      needed to explore whether PET can predict patient outcome of various lung cancer
      patients receiving different treatment regimens.

PMID- 14731330
TI  - Non-small-cell lung cancer have we reached a "chemotherapy efficacy plateau"?

PMID- 14731328
TI  - How can we improve survival rate for patients with non-small-cell lung cancer?

PMID- 14731331
TI  - 36th Annual ASCO Meeting. New Orleans, LA. May 2000.

PMID- 14731333
TI  - Irinotecan and cisplatin versus etoposide and cisplatin in small-cell lung
      cancer: JCOG 9511.

PMID- 14731332
TI  - Phase II and III trials: comparison of four chemotherapy regimens in advanced non
      small-cell lung cancer (ECOG 1594).

PMID- 14731334
TI  - Concurrent chemoradiotherapy followed by consolidation docetaxel in stage IIIB
      non small-cell lung cancer (SWOG 9504).

PMID- 14731335
TI  - Treatment of brain metastases in patients with small-cell lung cancer: lessons
      from treatment of other tumors.
AB  - Brain metastases are common in patients with small-cell lung cancer (SCLC) and
      are usually fatal. About half of all patients who develop brain metastases will
      remain symptomatic at their time of death, even if the immediate cause of death
      is not neurologic. While it has been argued that the obtundation that sometimes
      comes with brain metastases may be a relatively easy way to die, studies which
      have examined the quality of life of individuals developing brain metastases
      dispute this. For most patients and their families, the impairment of physical,
      cognitive, and affective function which accompanies most brain metastases is
      highly distressing and can be seen as a "loss" of the patient even before his/her
      death. Thus, improved treatment of overt brain metastases will be of palliative
      value, and eradication of microscopic disease in the brain may cure patients
      whose disease in other sites has been eradicated. Prophylactic cranial
      irradiation (PCI) for patients who have achieved a complete response to induction
      therapy markedly reduces the risk of central nervous system relapse and modestly
      but significantly improves survival. Despite the use of PCI, many patients with
      SCLC will develop brain metastases, and there is increasing interest in surgical
      treatment of patients with solitary lesions and the use of systemic chemotherapy
      in treating patients, with both SCLC and non small-cell lung cancer, who have
      multifocal brain metastases which are minimally symptomatic, particularly when
      these patients also have extracranial metastatic disease.

PMID- 14731336
TI  - The role of gemcitabine and paclitaxel as second-line chemotherapy for the
      treatment of advanced non small-cell lung cancer (NSCLC).
AB  - Second-line chemotherapy with the newer active anticancer drugs like docetaxel
      may confer some benefit in patients with non small-cell lung cancer (NSCLC) who
      failed front-line treatment with cisplatin-contain-ing chemotherapy regimens.
      However, young patients with good performance status need further efforts for
      palliation and, probably, survival prolongation. Phase II trials have shown that
      gemcitabine, a new nucleoside analogue, is effective as second-line treatment
      with a 7%-25% objective response and a 22- to 33-week median survival in patients
      with NSCLC. Paclitaxel also seems to be active as second-line treatment with a 3%
      38% objective response and 17- to 40-week median survival. The antitumor activity
      of second-line paclitaxel seems to be dose related. The combination of
      gemcitabine (900 mg/m2 on days 1 and 8) and paclitaxel (175 mg/m2 on day 8) every
      3 weeks was administered in 49 patients pretreated with cisplatin- and/or
      docetaxel-based chemotherapy. Objective responses were observed in 18% (95%
      confidence interval: 4%-24%) of the patients (one complete response and eight
      partial responses); three of the responses were observed in patients who failed
      to respond to front-line chemotherapy. The median survival was 44 weeks. The
      toxicity profile of the regimen was mild with grade 3/4 neutropenia and
      thrombocytopenia occurring in 12% and 2% of the patients, respectively. There was
      only one episode of neutropenic fever. Grade 2 and 3 neurotoxicity occurred in
      24% and 8% of the patients, respectively, and 51% of the patients reported grade
      2 and 3 asthenia. In conclusion, the combination of gemcitabine/paclitaxel is an
      effective and well-tolerated second-line chemotherapy regimen which can be given
      on an outpatient basis.

PMID- 14731337
TI  - Pilot and safety trial of carboplatin, paclitaxel, and thalidomide in advanced
      non small-cell lung cancer.
AB  - We performed a pilot study to assess the safety of thalidomide in combination
      with standard chemo-therapy in patients with advanced non small-cell lung cancer.
      Patients with unresectable stage IIIA, IIIB, or IV disease were enrolled starting
      in July 1999. Patients received paclitaxel 225 mg/m2 over 3 hours and carboplatin
      area under the curve = 6.0 with thalidomide at a starting daily dose of 200 mg.
      The thalidomide dose was escalated, if tolerated, by 200 mg per week to a target
      dose of 1000 mg per day and could continue for up to 6 months. Patients with
      stages IIIA and IIIB disease without effusion received radiotherapy with
      concurrent thalidomide after 2 cycles of chemotherapy. Nine patients were
      enrolled: one with IIIA disease, three with IIIB disease, and five with stage IV
      disease. Five of nine patients had previously been treated with chemotherapy
      and/or radiotherapy. The most frequent side effects noted were fatigue, myalgia,
      constipation, neuropathy, and myelosuppression. Sixteen of the 17 (94%) episodes
      of grade 3 or 4 hematologic toxicity occurred in the five patients who had
      previously received chemotherapy, although no patients developed neutropenic
      fever. The median tolerated daily thalidomide dose was 600 mg. One patient with
      IIIA disease had a partial response after 2 cycles of chemotherapy and went on to
      receive radiotherapy with thalidomide. One patient with stage IV disease
      continues on this study with stable disease at 187 days. The median time to
      progression was 118 days. This preliminary data supports the further
      investigation of this combination in chemotherapy-naive patients with advanced
      non small-cell lung cancer.

PMID- 14731340
TI  - Total videothoracoscopic lobectomy versus open thoracotomy for early-stage non
      small-cell lung cancer.
AB  - Lobectomy remains the standard procedure for early-stage non small-cell lung
      cancer (NSCLC). Advances in minimally invasive surgery allow lobectomy to be
      performed by videothoracoscopy (VATSLOBE). The objective of this study was to
      compare open thoracotomy (OPENLOBE) to VATSLOBE in the treatment of early-stage
      NSCLC. A retrospective review over a 6-year period at a single tertiary care
      center identified 31 patients treated by VATSLOBE. A comparison was made with 31
      patients undergoing OPENLOBE during the same time period. The cases were matched
      for age, pulmonary function testing, tumor size, and comorbidities. The VATSLOBE
      technique was carried out using four 1 cm thoracoports, one of which was enlarged
      to a 4-6 cm access incision for lobe retrieval. OPENLOBE was performed by
      standard posterolateral thoracotomy. The VATSLOBE group had a longer operative
      time (214.03 min) compared to OPENLOBE (140.67 min). There was no difference in
      the extent of lymph node dissection or in morbidity between the two groups.
      VATSLOBE patients had their chest tubes removed earlier (4.77 vs. 8.16 days) and
      stayed in the hospital for a shorter time (7.07 vs. 11.94 days) compared to
      OPENLOBE patients. In this retrospective review, lobectomy performed by the
      videothoracoscopic approach was comparable to OPENLOBE in terms of lymph node
      dissection, morbidity, and long-term survival. VATSLOBE had the advantages of a
      shorter hospital stay and fewer days with a chest tube. Minimally invasive
      surgery for early-stage lung cancer should be further investigated in multi
      institutional controlled trials.

PMID- 14731342
TI  - Phase II study of pyrazine diazohydroxide (NSC 361456) for advanced non small
      cell lung cancer.
AB  - Pyrazine diazohydroxide (NSC 361456) (PZDH) was selected for further development
      after demonstrating more stability than its parent compound and significant
      antitumor activity in a number of in vivo tumor models. Its proposed mechanism of
      action is through the formation of DNA adducts via the reactive pyrazine
      diazonium ion. The aim of this phase II trial was to determine the toxicity and
      antitumor activity of PZDH in advanced non small-cell lung cancer (NSCLC). From
      May 1995 through April 1996, 17 chemo-therapy-naive patients were entered into
      this study. PZDH was administered via a 5-minute intravenous bolus injection at a
      dose of 100 mg/m2 for 5 days and repeated every 42 days. Per interim guidelines,
      the study was closed early due to lack of activity. Seventeen patients were
      evaluable for toxicity while 15 patients were evaluable for response. The median
      number of cycles administered was 2 (range, 1-7). Toxicity was moderate with
      grade 3-4 thrombocytopenia being the most common and occurring in six of 17
      patients. Of the 15 patients evaluable for response, no partial or complete
      responses were observed (95% confidence interval [CI]: 0%-22%), while seven
      patients had stable disease and eight patients progressed during therapy. All but
      one patient have died. The median survival for the group is 6.6 months (95% CI:
      3.4-10.8 months). PZDH possesses modest but acceptable hematologic toxicity when
      delivered at the above dose and dosing scheme. Our results demonstrate that PZDH
      has no clinical activity in advanced NSCLC with this dose and schedule.

PMID- 14731345
TI  - HER2/neu peptide-based vaccines, with GM-CSF as an adjuvant, in patients with
      advanced-stage HER2/neu-expressing cancers.

PMID- 14731343
TI  - Randomized trial of surgery versus radiotherapy in patients with stage IIIA (N2)
      non small-cell lung cancer after a response to induction chemotherapy. EORTC
      08941.
AB  - Combined modality treatment of patients with stage III non small-cell lung cancer
      (NSCLC) has recently become widely accepted. Standard combinations are
      neoadjuvant chemotherapy followed by radiotherapy or concurrent chemotherapy and
      radiotherapy. The effect of combined modality treatment on survival is dependent
      on both the efficacy of chemotherapy to eradicate micrometastases and optimal
      local control. The European Organization for Research and Treatment of Cancer
      (EORTC) Lung Cancer Cooperative Group has chosen to investigate in a comparative
      way the side effects and the effect on survival of radiotherapy versus surgery in
      stage IIIA (N2) NSCLC.

PMID- 14731346
TI  - [Improving clinical research of arrhythmia in children].

PMID- 14731347
TI  - [A novel KCNQ1 mutation in Chinese with congenital long QT syndrome].
AB  - OBJECTIVE: Congenital long QT syndrome (LQTS) is an inherited disorder of cardiac
      repolarization characterized by prolongation of QT interval and polymorphic
      ventricular tachycardia torsade de pointes (TdP) in the electrocardiogram (ECG).
      Clinical symptoms include recurrent syncope, seizure or even sudden death. It is
      caused by mutations of at least seven genes, six of them encoding ion channels
      that determine the duration of ventricular action potentials. One of these genes,
      KCNQ1, encodes an alpha-subunit of cardiac slowly activated delayed rectifier
      potassium channel. Patients carrying mutations of KCNQ1 are named as LQT1, which
      accounts for 42% of patients with LQTS. This study sought to analyze the clinical
      data of Chinese with LQTS and to screen for the mutations of KCNQ1. METHODS: The
      universally accepted phenotypic criteria of LQTS was used for identification of
      probands. There were six families with LQTS. They were enrolled in this study.
      Clinical and ECG data of each family member were recorded. Genomic DNA was
      prepared from peripheral blood lymphocytes. Polymerase chain reaction-single
      strand conformation polymorphism analysis was used to screen for mutations
      throughout the whole coding region of KCNQ1 and DNA sequencing was performed to
      determine the exact mutation site. RESULTS: There were totally 13 patients in the
      six LQTS families. Five were male and eight female. One suffered from sudden
      death, 10 had syncope and 2 were asymptomatic. Eleven of the 13 patients had ECG
      data. Their QT and QTc (mean +/- SD) were (0.460 +/- 0.058) s and (0.516 +/-
      0.058) s, respectively. TdP was observed in 3 patients (27%) during the syncope
      attack. By PCR-SSCP analysis, two novel KCNQ1 deletion mutations 356-357 Delta QQ
      and 626-631 Delta GSGGPP were identified in 7 patients of 2 families. None of 50
      normal individuals carried these mutations, indicating these two mutations were
      likely to cause the disease. In addition, P448R was found in one affected and
      some unaffected members in other two families and in 7 of 50 (14%) normal
      individuals, indicating that this might be a polymorphism. All the three
      mutations located in C-terminal domain of KCNQ1 protein. CONCLUSIONS: Two novel
      deletion mutations and one novel polymorphism of KCNQ1 gene were identified among
      6 Chinese families with LQTS.

PMID- 14731348
TI  - [Arrhythmia in the long-term follow-up after intracardiac repair of tetralogy of
      Fallot].
AB  - OBJECTIVE: The long-term success of intracardiac repair of tetralogy of Fallot is
      hampered by the occurrence of arrhythmias. The aim of the present study was to
      determine the incidence of arrhythmias after intracardiac repair of tetralogy of
      Fallot and their correlation with surgical and clinical findings. METHODS: The
      study group consisted of 54 patients, 35 males and 19 females. They underwent
      repair at a mean age of 51 months (range 17 to 117 months). The median age at the
      time of study was 9.4 years (range 5 to 14 years), and the mean duration of
      follow-up was 4.3 years (range 2.8 to 9.0 years) after surgery. The follow-up
      study included routine ECG, 24 hour Holter, echocardiography and exercise
      testing. RESULTS: The incidence of ventricular arrhythmia was 33 percent, and 1
      patient had non-sustained ventricular tachycardia. All patients with elevated
      right ventricular pressure had ventricular arrhythmias, and 28% of patients with
      normal right ventricular pressure had ventricular arrhythmias (P < 0.05). 53% of
      patients had significant ventricular arrhythmias when the duration of
      cardiopulmonary bypass was > or = 90 minutes, as opposed to 23% when it was < 90
      minutes (P < 0.05). There was no significant difference in prevalence of
      ventricular arrhythmias between mild pulmonary regurgitation and severe pulmonary
      regurgitation (21% vs 40%, P > 0.05). No significant difference was found in the
      incidence of ventricular arrhythmias between follow-up in five years and more
      than five years (32% vs 34%, P > 0.05). Age at surgery correlated with the
      prevalence of ventricular arrhythmias (r = -0.221, P < 0.05). Eight patients
      (15%) had supraventricular arrhythmias. CONCLUSION: The frequency of ventricular
      arrhythmias correlated with elevated right ventricular systolic pressure, the
      duration of cardiopulmonary bypass, and the age at surgery. No correlation was
      found between pulmonary regurgitation and the duration of follow-up. Exercise
      induced frequent multiform premature ventricular complexes were associated with
      abnormal hemodynamic status and high risk of ventricular tachycardia.

PMID- 14731349
TI  - [von Willebrand disease: a case report].

PMID- 14731351
TI  - [Progress in the clinical use of anti-arrhythmic drugs (I)].

PMID- 14731350
TI  - [Ablation of postoperative "incisional" reentrant atrial tachycardia and flutter
      in children using the CARTO system].
AB  - OBJECTIVE: In children with congenital heart diseases who have undergone surgical
      interventions, postoperative arrhythmias frequently complicate the clinical
      course. "Incisional" atrial tachycardia or flutter is one of the most common
      forms of postoperative arrhythmias in these patients and can lead to significant
      morbidity and even mortality. The aim of this study was to investigate how to use
      antiarrhythmic drugs and the CARTO system to treat these cases. METHODS: There
      were 12 patients with "incisional" atrial tachycardia or flutter complicating
      surgery for congenital heart diseases in this study (3 patients with correction
      of tetrology of Fallot, 3 with atrial septal defect repair, 2 with ventricular
      septal defect repair, 1 with switch, 1 with repair of Ebstein's anomaly, 1 with
      total anomalous pulmonary venous drainage, and 1 with atrial septal closure with
      the Amplatzer septal occlusion). Patients whose body weight was less than 10 kg
      or those who did not wish to accept ablation were treated with antiarrhythmic
      drugs, including digitoxin, propranolol, metoprolol and cordarone. CARTO system
      was used to map 6 patients whose body weight was more than 10 kg and who agreed
      with accepting ablation for atrial tachycardia and flutter. Radio-frequency
      ablation was performed in these 6 cases including two cases of "incisional"
      atrial tachycardia and 4 of atrial flutter. RESULTS: (1) The antiarrhythmic drug
      was successful in 6 patients with "incisional" atrial tachycardia. (2) Six
      patients including 2 children with "incisional" atrial tachycardia and 4 children
      with atrial flutter were successfully ablated. But one case of "incisional"
      atrial tachycardia relapsed after 3 months of ablation. This case, however, was
      successfully ablated again later. No further relapse was observed during the 2 -
      24 months of follow-up. CONCLUSION: Ablation of "incisional" atrial tachycardia
      and flutter is the first choice to treat the patients whose body weight is more
      than 10 kg and those who agree with accepting ablation by CARTO system. Drug
      therapy of "incisional" atrial tachycardia and flutter is palliative and it is
      the only selection to treat the patients whose body weight is less than 10 kg or
      those who do not wish to accept ablation procedure.

PMID- 14731352
TI  - [Evaluation of diagnostic criteria for infective endocarditis:an analysis of 216
      pathologically proven patients].
AB  - OBJECTIVE: Eighteen to twenty-four percent of patients with infective
      endocarditis (IE) proved pathologically were clinically possible IE by the Duke
      criteria. In order to improve the sensitivity, the new criteria (trial) for the
      diagnosis of IE was proposed by Pediatric Cardiology Association of China and
      Editorial Committee of Chinese Journal of Pediatrics. The aim of this study was
      to evaluate and compare the value of the new criteria (trial) for the diagnosis
      of IE with the Duke criteria. METHODS: Group A consisted of 193 patients proved
      with IE at autopsy or surgery, where the cases had the results of blood culture
      and echocardiography data, and Group B had 23 patients with clinical diagnosis of
      IE in whom evidence of IE was not found at surgery. All the above cases were
      collected from 15 hospitals. They were analyzed and classified by the new
      criteria and at the same time by the Duke criteria. The sensitivity and
      specificity of both criteria for the diagnosis of IE were compared. RESULTS: (1)
      In Group A, same microorganisms were detected twice in blood culture in 50
      patients (25.9%), while 36 patients (18.7%) had only one positive blood culture.
      Endocardial involvement was found by echocardiography in 165 cases (85.5%),
      including vegetation in 160 (82.9%), perforation of aortic valve in 4 (2.1%), and
      partial dehiscence of ventricular septal defect (VSD) patch in one (0.5%).
      Vegetation appeared oscillating masses in 100 cases (62.5%). One hundred and
      eighty (93.3%) patients had predisposing heart conditions, and 151 (72.8%) with
      congenital heart diseases. Fever was revealed in 178 cases (92.2%). Vegetation or
      perforation of aortic valve was detected in all patients without fever. Heart
      failure was complicated in 91 patients, 7 of whom had no fever. Vascular
      phenomena including petechiae and major arterial emboli occurred in 21 and 28
      cases, respectively. Among immunologic phenomena, glomerulonephritis occurred in
      9, elevated rheumatoid factor in 17/25 and elevated CRP in 51/71. In Group B, the
      same microorganism was detected in blood culture twice in only 3 patients and 2
      patients had one positive blood culture. Vegetation in tricuspid valve was found
      by echocardiography in one patient. (2) Ninety-four cases (48.7%) of Group A were
      clinically confirmed IE by the Duke criteria. The diagnosis was made on the basis
      of two major criteria in 42, one major and 3 minor criteria in 52.14 of 99 as
      possible IE were excluded by the modified Duke criteria. On the other hand, a
      definite diagnosis of IE was made in 156 patients (80.8%) by the new criteria. Of
      them, 94 met with definite criteria of the Duke criteria, 62 (32%) met with
      echocardiographic evidence of endocardial involvement (major criteria) and two
      minor criteria. No patient of Group B was clinically definite with the Duke
      criteria, but one patient was clinically definite with the new criteria (trial).
      (3) The sensitivity and specificity for the diagnosis of IE were 80.8% and 95.7%,
      respectively, with the new criteria (trial), 48.7% and 100%, respectively, with
      the Duke criteria. CONCLUSION: With the addition of echocardiographic evidence of
      endocardial involvement (major criteria) and 2 minor criteria as definite
      diagnostic criteria, the sensitivity of the new criteria (trial) is superior to
      that of the Duke criteria, but there is no significant difference in specificity
      for the diagnosis of IE between the two criteria.

PMID- 14731353
TI  - [Expression of tumor necrosis factor-alpha and nuclear factor-kappa B in
      childhood ulcerative colitis].
AB  - OBJECTIVE: It has been proposed that aberrant immunity of local bowel mucosa may
      cause ulcerative colitis (UC) and the tumor necrosis factor-alpha (TNF-alpha) and
      nuclear factor-kappa B (NF-kappa B) may play a role in the development of this
      disease. To investigate the role of TNF-alpha and NF-kappa B in childhood UC, the
      expression of TNF-alpha and NF-kappa B in the bowel mucosa and their relationship
      were studied. METHODS: Using anti-CD68, anti-TNF-alpha and anti-NF-kappa Bp65
      antibodies, the cytokine immunoreactivities in the bowel mucosa of 39 cases of
      childhood UC (active UC: n = 21, non-active UC: n = 18) were detected by
      immunohistochemistry. The control specimens of normal bowel mucosa were collected
      from 7 cases with colorectal polyp or abdominal pain by sigmoidoscopy. RESULTS:
      The numbers (median: interquartile range) of CD68(+) cells, TNF-alpha(+) cells
      and NF-kappa Bp65(+) cells were 44.0 (31.5 - 48.2), 42.7 (19.5 - 65.0) and 50.7
      (30.0 - 58.0) in the active UC mucosa, and were 9.2 (7.9 - 16.6), 5.5 (2.5 - 9.1)
      and 4.2 (3.0 - 8.4) in non-active UC mucosa, and 5.3 (4.3 - 8.7), 3.0 (0.0 - 6.3)
      and 3.3 (0.0 - 4.0) in the control mucosa, respectively. The levels of CD68, TNF
      alpha and NF-kappa Bp65 expressions in the active UC were significantly higher
      than those in the non-active UC (P < 0.001) and the controls (P < 0.001). The
      expression level of CD68 in non-active UC was much higher than that in the
      controls (P = 0.008). Using the correlation analysis, a positive correlation
      between TNF-alpha and NF-kappa B activation was found (r = 0.885, P < 0.001).
      CONCLUSIONS: Macrophages TNF-alpha and NF-kappa B may play an important role in
      the pathophysiologic mechanism of childhood active UC. The activation of NF-kappa
      B may be associated with the release of TNF-alpha.

PMID- 14731354
TI  - [Intracranial hemorrhage caused by delayed-onset vitamin K deficiency in
      consecutive two gestations infants].

PMID- 14731355
TI  - [Diagnostic value of serum high molecular weight alkaline phosphatase in early
      detection of cholestatic jaundice in neonates].
AB  - OBJECTIVE: To investigate the difference of serum high molecular weight alkaline
      phosphatase (HMAP) levels between biliary atresia (BA) and neonatal hepatitis
      (NH), and to develop a new differential method and early diagnostic indicators
      for cholestatic jaundice in neonates. METHODS: Totally 31 patients with
      cholestatic jaundice seen between Aug. 2000 and Feb. 2002, including 15 cases
      with BA, 16 cases with NH, 30 healthy infants and 30 infants with non-cholestatic
      jaundice were enrolled in this study. Serum samples were obtained from each
      subject by using venipuncture. The samples were stored at -80 degrees C and
      analyzed within 6 months. A murine hybridoma producing monoclonal antibody to
      human high molecular weight alkaline phosphatase (MoAb HMAP-1) was prepared by
      using partially purified HMAP from human serum as the immunogen. The antibody did
      not cross-react with other alkaline phosphatase (ALP) isozymes. A monoclonal
      antibody immunocatalytic assay for HMAP in serum was developed by using MoAb HMAP
      1 bound to nitrocellulose membrane discs. The serum total ALP (TALP) and gamma-GT
      were determined in the meantime, the hepatobiliary ultrasonography and
      scintigraphy were performed too. The data were analyzed with t test, chi-square
      test and percentage. Comparisons were made between BA and NH with their
      sensitivity and specificity in different methods. RESULTS: Serum HMAP was
      detected in 14 of 15 patients of BA, in 2 of 16 NH patients, while in none of the
      healthy control group. The positive ratios of serum HMAP in BA and NH were 93.3%
      and 12.5%, respectively (P < 0.005). The sensitivity and specificity of serum
      HMAP in BA and NH were 93.3% and 87.5%, respectively. The sensitivity and
      specificity of TALP, gamma-GT and hepatobiliary scintigraphy were 80.0%, 73.3%,
      86.7% and 62.5%, 68.8%, 62.5%, respectively, which were clearly lower than those
      of serum HMAP. CONCLUSIONS: The determination of serum HMAP was more sensitive
      and specific than the other methods tested. Therefore the method can be used as a
      useful indicator for cholestatic jaundice in neonates, although it needs further
      study.

PMID- 14731356
TI  - [Association between vitamin D receptor gene polymorphism and the susceptibility
      of children to lead].
AB  - OBJECTS: To investigate the distribution of vitamin D receptor (VDR) genotypes
      among the Hans of a lead contaminated mine in Shanxi and explore the relationship
      between blood lead levels and the genetic polymorphism of VDR gene. METHODS: VDR
      genotypes were determined by polymerase-chain-reaction and restrictive fragment
      length polymorphism (PCR-RFLP) and the blood lead level was measured by using the
      graphite furnace atomic absorption spectrometry in a population of 120 pre-school
      children aged 5 - 6 years who were from the mine kindergarten and were unrelated
      Hans. An environmental questionnaire in relation to blood lead level was filled
      for each subject. RESULTS: (1) The gene distribution of the VDR phenotypes in
      these children was VDRBB, 1.7%; VDRBb, 9.2%; VDRbb, 89.2%. (2) The mean blood
      lead level of the children who had VDR B allele [(0.910 8 +/- 0.265 0)
      micromol/L] was significantly higher than that whose VDR genotype was bb [(0.740
      1 +/- 0.270 1) micromol/L (mean +/- standard deviation)] (t = 2.155, P < 0.05).
      (3) Many factors were found to affect the blood lead levels, such as the VDR
      genotype, the type of fuel, educational level of mothers and so on. After
      controlling the possible confounding variables by multiple regression, the
      contribution of the VDR phenotype to the blood lead levels was still
      statistically significant. CONCLUSION: These results indicated that the frequency
      distribution of the VDR genotype in these children was apparently different from
      that in Caucasians who had high frequencies of VDR B. The results also indicated
      that the individuals carrying the VDR B allele were more susceptible to lead
      poisoning.

PMID- 14731357
TI  - [Apolipoprotein E gene expression in peripheral blood monocyte in children with
      obesity].
AB  - OBJECTIVE: Coronary heart disease (CHD) is one of the most common causes of death
      in the world. Some studies suggested that CHD begins in childhood. Obesity and
      dyslipidemia are important risk factors of coronary heart disease. Apolipoprotein
      (apo)E gene associated with dyslipidemia and coronary heart disease. The present
      study was designed to investigate the expression status of apoE gene in
      peripheral blood monocyte and association of apoE gene expression with lipids in
      children with obesity. METHODS: Among 32 children with obesity and 32 healthy
      children without obesity or overweight, ApoE gene expressions were determined by
      competitive reverse transcription-polymerase chain reaction in peripheral blood
      monocyte. The concentrations of plasma triglyceride, total cholesterol, low
      density lipoprotein-cholesterol, high density lipoprotein-cholesterol,
      lipoprotein(a), apoA I, apoB(100) and apoE were measured. RESULTS: Expression of
      apoE gene was detected in peripheral blood monocyte. Expression of apoE gene was
      significantly reduced in children with obesity as compared with control group
      (0.29 +/- 0.14 moles/mole GAPDH mRNA vs. 0.36 +/- 0.10 moles/mole GAPDH mRNA, t =
      2.15, P < 0.05). The more severe was the degree of obesity, the more
      significantly reduced the expression of apoE gene; the degree of obesity was
      negatively correlated with the levels of expression of apoE gene (correlation
      coefficient = -0.40, P < 0.05). Compared with control group, the levels of
      triglyceride, total cholesterol, low density lipoprotein-cholesterol, and
      apoB(100) were higher, and those of high density lipoprotein-cholesterol, apoA I
      and apoE were lower in children with obesity [(1.68 +/- 0.50) mmol/L vs. (0.99 +/
      0.54) mmol/L, (4.47 +/- 0.91) mmol/L vs. (3.33 +/- 0.90) mmol/L, (2.23 +/- 0.71)
      mmol/L vs. (1.13 +/- 0.96) mmol/L, (94.48 +/- 9.97) mg/dl vs. (83.81 +/- 15.64)
      mg/dl, (1.47 +/- 0.39) mmol/L vs. (1.73 +/- 0.36) mmol/L, (112.71 +/- 27.86)
      mg/dl vs. (134.80 +/- 45.36) mg/dl, (24.50 +/- 10.92) mg/L vs.(35.07 +/- 9.79)
      mg/L, respectively, P < 0.05]. ApoE gene expression was associated with plasma
      lipids metabolism in children with obesity. The quantity of apoE gene expression
      was inversely associated with low density lipoprotein-cholesterol, positively
      correlated with apoE (correlation coefficient = -0.33, 0.35, respectively, P <
      0.05). The quantity of apoE gene expression was not associated with total
      cholesterol, triglyceride, high density lipoprotein-cholesterol, lipoprotein(a),
      apoA I, and apoB(100) (correlation coefficient = -0.19, -0.11, 0.16, 0.09, 0.18,
      0.22, P > 0.05). CONCLUSION: Expression of apoE gene was significantly reduced in
      peripheral blood monocyte in children with obesity. The quantity of apoE gene
      expression was associated with degree of obesity and abnormality of blood lipids.

PMID- 14731359
TI  - [A case of hemolytic anemia induced by dipterex].

PMID- 14731358
TI  - [Effects of combined surfactant and inhaled nitric oxide in ventilated rabbits
      with meconium aspiration-induced acute lung injury].
AB  - OBJECTIVE: To evaluate dose response of inhaled nitric oxide (iNO) for surfactant
      treated rabbits with meconium aspiration-induced acute lung injury (ALI) and
      hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous
      NO delivery in pressure support ventilation (PSV). METHODS: Adult rabbits (2.0 -
      3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation
      for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups:
      Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min
      interval of disconnection; Surf, intratracheal instillation of porcine lung
      surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO
      and Surf groups; and a normal group (N), which did not undergo meconium
      aspiration but received sham deliveries of normal saline. All the animals were
      treated with PSV for 6 h. iNO levels at different input and sampling sites in the
      NO and SNO groups were detected by on-line chemiluminescent technique. The blood
      gas and lung mechanics were measured during the experiments every 2 h. RESULTS:
      (1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and
      depressed dynamic compliance of respiratory system (Cdyn) and airway resistance
      (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In
      the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at
      baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement
      was observed in both Surf and NO groups. Cdyn and Raw were only improved for
      short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6)
      to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40
      x 10(-6). The response of iNO in NO group was relatively transient compared to
      the SNO group. (2) When iNO was connected to the ventilator circuit, the
      connected site should be placed before humidifier to minimize fluctuation of iNO
      concentration, and sampling site for iNO monitoring should be placed adequately
      to eliminate artifact. CONCLUSIONS: iNO synergistically improved surfactant
      effects on oxygenation and lung mechanics. Continuous supply of iNO with non
      continuous flow ventilator provided stable NO within accepted target range with
      least variation.

PMID- 14731360
TI  - [Myocardial impairment in asphyxiated newborn piglets].
AB  - OBJECTIVE: To establish a piglet model of acute hypoxic myocardial impairment.
      METHODS: Nineteen newborn piglets were divided into two groups: control group
      (CON, n = 8) and asphyxia group (ASP, n = 11). In ASP group, asphyxia was induced
      by disconnecting the animal from the ventilator and clamping the inhalation
      tubing for 10 minutes. Six hours after cardiopulmonary resuscitation (CPR), the
      levels of serum creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were
      detected. Cardiac functions were evaluated by echocardiography. Parameters
      included left ventricular ejection fraction (LVEF), right ventricular ejection
      fraction (RVEF), ratio of peak E velocity and peak A velocity of mitral flow and
      tricuspid flow (MVE/A and TVE/A), ratio of peak velocity and a velocity of mitral
      annulus motion and tricuspid annulus motion (MVe/a and TVe/a), isovolumic
      relaxation time of left ventricle (LVIRT), index of mitral regurgitation and
      tricuspid regurgitation (MR and TR). The CON group was examined at the
      corresponding time points. The pathologic changes in piglets' hearts were
      examined. The myocardial histopathologic damage score (MHDS) was used to evaluate
      the severity of myocardial impairments. RESULTS: Six hours after CPR, the CK-MB
      and cTnT in ASP group [(423 +/- 156) IU/L and (0.85 +/- 0.64) microg/L] were both
      higher than those in CON group [(213 +/- 30) IU/L and (0.08 +/- 0.02) microg/L, P
      < 0.01]. The LVEF, RVEF, TVE/A, MVe/a and TVe/a in ASP group [(59.6 +/- 8.6)%,
      (60.2 +/- 7.1)%, 0.79 +/- 0.21, 0.77 +/- 0.12 and 0.78 +/- 0.19, respectively]
      were all lower than those in CON group [(67.5 +/- 6.9)%, (68.8 +/- 7.4)%, 1.14 +/
      0.16, 1.19 +/- 0.18 and 1.03 +/- 0.27, respectively, P < 0.05]. The MHDS in ASP
      group was higher (2.82 +/- 0.98) than that in CON group (0.38 +/- 0.53, P <
      0.01), but no significant difference was observed in MHDS between the left
      ventricle and right ventricle. CONCLUSION: Asphyxia can lead to obvious
      myocardial impairment in newborn piglet, which could be very useful for the
      studies of acute hypoxic myocardial impairment in the newborn infants.

PMID- 14731361
TI  - [A study on myocardial Pax-8 gene].
AB  - OBJECTIVE: Conventional deletion of ALK3, also termed as bone morphogenetic
      protein (BMP) receptor IA, in mice might result in early embryonic lethality. To
      investigate the function of ALK3 in cardiac development, the cardiac-specific
      deletion of ALK3 in mice was made by Dr. Schneider, using Cre recombinase driven
      by the alpha-MHC promoter that Dr. Fukushipe worked out. Such specific deletion
      of ALK3 caused death in mid-gestation with defects in the trabeculae,
      interventricular septum, and endocardial cushion. Since ALK3 is not a cardiac
      specific gene, it is extremely important to identify ALK3 downstream genes.
      METHODS: Alpha-MHC Cre+/-, ALK3 F/- and alpha-MHC Cre+/-, ALK3 F/+ embryos were
      obtained after 20 alpha-MHC Cre+/-, ALK3 +/- mice and 20 ALK3 F/F mice were
      mating. The ALK3 downstream genes were screened using microarray made in Germany
      that could identify 25000 genes in mouse. Two populations of mRNA, one derived
      from the embryonic heart (11.5 days) of alpha-MHC Cre+/-, ALK3 F/- mice, and the
      other derived from the alpha-MHC Cre+/-, ALK3 F/+ mice, were compared. Cardiac
      specific ALK3 downstream genes were identified using real time quantitative RT
      PCR and in situ hybridization. RESULTS: The expression of 12 genes, such as Pax-8
      and Hox-3.5 were down-regulated in alpha-MHC Cre+/-, ALK3 F/- mouse heart. The
      expression of 16 genes including Ras-related protein Rab-5b and EPS-8 protein was
      up-regulated in the group of alpha-MHC Cre+/-, ALK3 F/-. It was found that the
      Box protein Pax-8 gene was down-regulated by 7.1 fold (P < 0.001) in the alpha
      MHC Cre+/-, ALK3 F/- mice by real time quantitative RT-PCR. It was also revealed
      that the Box protein Pax-8 gene was expressed stronger in alpha-MHC Cre+/-, ALK3
      F/+ than alpha-MHC Cre+/-, ALK3 F/- E11.5 days mouse heart by means of in situ
      hybridization. CONCLUSION: The Box protein Pax-8 gene is an important and cardiac
      specific ALK3 downstream gene in the BMP signaling pathway during inter
      ventricular septum development.

PMID- 14731362
TI  - [The relationship between Fas expression and lung injury after gut ischemia
      reperfusion injury].

PMID- 14731363
TI  - [The ages of tachycardia onset and associated factors for infants and children
      with supraventricular tachycardia].

PMID- 14731364
TI  - [Clinical analysis of coupled and paired ventric premature systole].

PMID- 14731365
TI  - [Clinical study of ventricular tachycardia in children].

PMID- 14731367
TI  - [Identification of right ectopic atrial tachycardia by non-invasive examination].

PMID- 14731366
TI  - [Sotalol in treatment of pediatric severe (refractory) cardiac arrhythmias].

PMID- 14731368
TI  - [Effects of a novel CPAP device on breathing and blood gases in newborns with
      pneumonia].

PMID- 14731369
TI  - [Moricizine in treatment of one case with tachycardia-induced cardiomyopathy].

PMID- 14731370
TI  - [Fibrodysplasia ossificans progressive (FOP): a case report].

PMID- 14731371
TI  - [A case clinic analysis of leukemoid reaction].

PMID- 14731372
TI  - [One case report of childhood acute lymphoblastic leukemia complicated with
      diabetes].

PMID- 14731373
TI  - [Clinical case discussion. No.113: Fever and cough for 2 months].

PMID- 14731374
TI  - [Study of hemophagocytic lymphohistiocytosis in children].

PMID- 14731375
TI  - [Lipid emulsion and lipid peroxidation].

PMID- 14731376
TI  - [Epstein-Barr virus infection and its related diseases].

PMID- 14731377
TI  - What is the best imaging strategy for acute stroke?
AB  - OBJECTIVES: To determine the cost-effectiveness of computed tomographic (CT)
      scanning after acute stroke. To assess the contribution of brain imaging to the
      diagnosis and management of stroke, and to estimate the costs, benefits and risks
      of different imaging strategies in order to provide data to inform national and
      local policy on the use of brain imaging in stroke. DESIGN: A decision-analysis
      model was developed to represent the pathway of care in acute stroke using 'scan
      all patients within 48 hours' as the comparator against which to cost 12
      alternative scan strategies. SETTING: Hospitals in Scotland. PARTICIPANTS:
      Subjects were patients admitted to hospital with a first stroke and those managed
      as outpatients. INTERVENTIONS: The effect on functional outcome after ischaemic
      or haemorrhagic stroke, tumours or infections, of correctly administered
      antithrombotic or other treatment; of time to scan and stroke severity on
      diagnosis by CT or MRI; on management, including length of stay, functional
      outcome, and quality-adjusted life years (QALYs), of the diagnostic information
      provided by CT scanning; the cost-effectiveness (cost versus QALYs) of different
      strategies for use of CT after acute stroke. MAIN OUTCOME MEASURES: Death and
      functional outcome at long-term follow-up; accuracy of CT and MRI; cost of CT
      scanning by time of day and week; effect of CT diagnosis on change in health
      outcome, length of stay in hospital and QALYs; cost-effectiveness of various
      scanning strategies. RESULTS: CT is very sensitive and specific for haemorrhage
      within the first 8 days of stroke only. Suboptimal scanning used in epidemiology
      studies suggests that the frequency of primary intracerebral haemorrhage (PICH)
      has been underestimated. Aspirin increases the risk of PICH. There were no
      reliable data on functional outcome or on the effect of antithrombotic treatment
      given long term after PICH. In 60% of patients with recurrent stroke after PICH,
      the cause is another PICH and mortality is high among PICH patients. A specific
      MR sequence (gradient echo) is required to identify prior PICH reliably. CT
      scanners were distributed unevenly in Scotland, 65% provided CT scanning within
      48 hours of stroke, and 100% within 7 days for hospital-admitted patients, but
      access out of hours was very variable, and for outpatients was poor. The average
      cost of a CT brain scan for stroke was pounds 30.23 to pounds 89.56 in normal
      working hours and pounds 55.05 to pounds 173.46 out of hours. Average length of
      stay was greatest for severe strokes and those who survived in a dependent state.
      For a cohort of 1000 patients aged 70-74 years, the policy 'scan all strokes
      within 48 hours', cost pounds 10,279,728 and achieved 1982.3 QALYS. The most cost
      effective strategy was 'scan all immediately' (pounds 9,993,676 and 1982.4
      QALYS). The least cost-effective was to 'scan patients on anticoagulants, in a
      life-threatening condition immediately and the rest within 14 days'. CONCLUSIONS:
      In general, strategies in which most patients were scanned immediately cost least
      and achieved the most QALYs, as the cost of providing CT (even out of hours) was
      less than the cost of inpatient care. Increasing independent survival by even a
      small proportion through early use of aspirin in the majority with ischaemic
      stroke, avoiding aspirin in those with haemorrhagic stroke, and appropriate early
      management of those who have not had a stroke, reduced costs and increased QALYs.

PMID- 14731378
TI  - Current pharmacologic approaches to treating neuropathic pain.
AB  - Most neuropathic analgesic medications have been introduced initially for other
      medical conditions. Anticonvulsants, local anesthetics, and antidepressants later
      were found to be effective in the treatment of neuropathic pain. Carbamazepine
      and the newer anticonvulsants such as gabapentin, lamotrigine, topiramate, and
      oxcarbazepine are being used as first-line or adjunctive therapy. The newer
      agents have less potential for drug interactions and a more favorable side-effect
      profile. Lidocaine administered systemically or topically is useful for some
      peripheral and central neuropathic pain conditions. The tricyclic antidepressants
      amitriptyline, nortriptyline, and desipramine have been shown to be effective for
      the management of neuropathic pain, independent of their antidepressant property.
      All of the available analgesics have considerable side effects, which necessitate
      careful titration. Future drug research may focus on developing medications
      specifically for neuropathic pain. These designer agents may have more desirable
      action without the unwanted side effects.

PMID- 14731379
TI  - Indomethacin-responsive headache syndromes.
AB  - Indomethacin-responsive headache syndromes represent a unique group of primary
      headache disorders characterized by a prompt and often complete response to
      indomethacin to the exclusion of other nonsteroidal anti-inflammatory drugs and
      medications usually effective in treating other primary headache disorders.
      Because these headache disorders can easily be overlooked in clinical practice,
      they likely are more common than previously recognized. Indomethacin-responsive
      headache syndromes can be divided into several distinct categories: a select
      group of trigeminal-autonomic cephalgias, valsalva-induced headaches, and primary
      stabbing headache (ice-pick headache or jabs and jolts syndrome). Each category
      can be differentiated clinically and by the extent to which the individual
      headache disorders respond to indomethacin. The paroxysmal and continuous
      hemicranias invariably respond in an absolute manner to indomethacin, whereas
      valsalva-induced and ice-pick headaches may respond in an equally dramatic, but
      somewhat less consistent fashion. Hypnic headache recently has been described as
      another primary headache disorder that may respond to indomethacin.

PMID- 14731380
TI  - Spinal agents for acute pain management.
AB  - This article describes the current and investigational agents for use in the
      treatment of acute pain. The use of spinal and epidural routes also are
      discussed.

PMID- 14731381
TI  - Pulsed radiofrequency neurotomy: advances in pain medicine.
AB  - In the past three decades, radiofrequency neurotomy (RFN) has been established as
      a safe and effective treatment for facet and sacroiliac arthropathy. However,
      early reports of deafferentation pain syndromes and motor deficit with the
      application of radiofrequency lesions to other neural structures effectively
      halted further development of this technology for other applications until recent
      years. Pulsed radiofrequency neurotomy (PRFN) represents the most recent advance
      in radiofrequency technology in clinical practice. PRFN allows for application of
      radiofrequency current at markedly lower tissue temperatures, thereby minimizing
      the risk of adverse events. The initial clinical data on PRFN demonstrate
      response rates similar to conventional high temperature RFN lesions for facet and
      sacroiliac arthropathy and a host of other chronic pain disorders.

PMID- 14731383
TI  - Radiation risk management during fluoroscopy for interventional pain medicine
      physicians.
AB  - Because of serious radiographic-induced skin injuries that may have been caused
      by the inappropriate use of fluoroscopy during the performance of radiograph
      guided invasive procedures, the US Food and Drug Administration (FDA) issued an
      advisory in 1994 suggesting that the key to preventing such unfortunate mishaps
      may be physician education, training, and credentialing in the safe operation of
      fluoroscopic equipment. The purpose of this article is to familiarize the
      interventional pain medicine physician with the physics of ionizing radiation and
      how to limit patient exposure through the optimum setting of tube current and
      voltage, the use of limited beam-on time, tight collimation, and the elimination
      of the nonessential use of the magnification mode on a fluoroscopy unit. In
      addition, the use of personal protection equipment and the knowledge needed to
      interpret the personal exposure record of each practitioner is discussed. All of
      this information will assist the interventional pain medicine physician in
      meeting the recommended FDA training and credentialing requirements.

PMID- 14731382
TI  - Treatment of cervicothoracic pain and cervicogenic headaches with regenerative
      injection therapy.
AB  - Significant progress has been made in interventional pain management. Despite
      this progress, patients continue to present a diagnostic and therapeutic
      challenge. Steroidal and nonsteroidal anti-inflammatory medications have limited
      use in degenerative painful conditions of connective tissue. Regenerative
      injection therapy, also known as prolotherapy, is a viable, type-specific
      treatment for such pathology. Several placebo-controlled studies, together with
      uncontrolled studies, indicate the effectiveness of regenerative injection
      therapy in treating painful ligament and tendon pathology. As stated in July 2003
      by Mooney, this treatment has advanced "from the fringe to the frontier of
      medical care."

PMID- 14731384
TI  - Chronic daily headache and the revised international headache society
      classification.
AB  - Chronic daily headache (CDH) is surprisingly common. It is best defined as a
      primary headache disorder with head pain on most days. There are a number of
      possible secondary causes of persistent headache, including traumatic, vascular,
      neoplastic, and infectious processes, all of which must be ruled out when the
      patient with frequent headache is evaluated. However, most patients with CDH seem
      to have a primary neurophysiologic disorder. This category of primary CDH does
      not seem to be a homogeneous disorder, but rather one with important subtypes.
      Several authors have proposed subdivisions of primary CDH such as chronic
      migraine, evolved migraine, transformed migraine, chronic tension-type headache,
      new daily persistent headache, and hemicrania continua. The International
      Headache Society (IHS) Classification published in 1988 did not address CDH other
      than to define a category "chronic tension-type headache." The revised IHS
      Classification (ICHD II) attempts to characterize CDH more thoroughly with the
      addition of chronic migraine and new daily persistent headache diagnoses, but
      this complex issue continues to defy easy categorization. This article provides a
      review of thinking about the nature of primary CDH and how ICHD II attempts to
      organize this category for much needed research purposes.

PMID- 14731385
TI  - Estrogen and chronic daily headache.
AB  - Estrogen exerts a strong influence on episodic headaches, such as migraine and
      tension-type headache. A relationship between sex hormones and chronic daily
      headache (CDH) is less well established. However, similarities between episodic
      and CDH suggest that estrogen also may significantly influence CDH.
      Pathophysiologic studies of CDH identify neurochemical abnormalities similar to
      those influenced by estrogen in episodic headache, such as aberrant 5
      hydroxytryptamine activity. In addition, gender differences in CDH prevalence in
      pediatric and adult populations support a hormonal influence. Few studies have
      evaluated the ability of gynecologic events, such as menses, to influence CDH.

PMID- 14731386
TI  - Children and adolescents with chronic daily headache.
AB  - Chronic daily headache is a significant problem in children and adolescents. The
      goal of this review is to paint a picture of this malady. The epidemiology is
      unclear because definitions have not been uniform. Classification systems reflect
      what is known in adults. Because the disease duration and the transformation
      period are so different in children with this disorder, shoehorning children into
      adult criteria may be problematic. Nevertheless, this article presents an
      approach to diagnosis and treatment based on what is present in the literature,
      what has worked with adults, and the consensus among pediatric headache
      practitioners. Because there is little literature on this subject, the review
      ends with a series of questions for future study.

PMID- 14731387
TI  - Learning the codes of fly immunity.
AB  - Insect antimicrobial response serves as an excellent model for studying human
      innate immunity. In this issue of Molecular Cell, Senger and colleagues
      demonstrate that a large number of immunity genes in Drosophila fat bodies can be
      regulated by a simple code, REL-GATA.

PMID- 14731388
TI  - Destruction with a box: substrate recognition by the anaphase-promoting complex.
AB  - Destruction boxes mark cyclin B and other proteins degraded in mitosis for
      ubiquitination by the anaphase-promoting complex (APC/C). In a paper in this
      issue of Molecular Cell, Yamano et al. show that destruction boxes directly bind
      to the APC/C in a cell cycle-regulated manner. Interestingly, this interaction
      does not require APC/C activators of the Cdc20 family, which were thought to be
      essential for recruiting substrates to the APC/C.

PMID- 14731389
TI  - Regulation of p53 by Mdm2: fate is in the numbers.
AB  - The p53 tumor suppressor protein is normally restrained by the Mdm2 oncoprotein,
      which promotes p53 ubiquitination. In a recent issue of Science, report that p53
      may face two alternative fates, depending on Mdm2 levels: high Mdm2 drives p53
      polyubiquitination and degradation within the cell nucleus, whereas low Mdm2
      promotes p53 monoubiquitination and nuclear exclusion.

PMID- 14731390
TI  - Indecent exposure: when telomeres become uncapped.
AB  - The protective "cap" that assembles at chromosome ends recruits and controls an
      intricate network of biochemical activities, each one critical for telomere
      structure and the maintenance of genomic stability. Recent studies have uncovered
      the components of telomere caps and have started to define the pathways that lead
      from telomere dysfunction to chromosomal catastrophe.

PMID- 14731391
TI  - Immunity regulatory DNAs share common organizational features in Drosophila.
AB  - Infection results in the rapid activation of immunity genes in the Drosophila fat
      body. Two classes of transcription factors have been implicated in this process:
      the REL-containing proteins, Dorsal, Dif, and Relish, and the GATA factor
      Serpent. Here we present evidence that REL-GATA synergy plays a pervasive role in
      the immune response. SELEX assays identified consensus binding sites that
      permitted the characterization of several immunity regulatory DNAs. The
      distribution of REL and GATA sites within these DNAs suggests that most or all
      fat-specific immunity genes contain a common organization of regulatory elements:
      closely linked REL and GATA binding sites positioned in the same orientation and
      located near the transcription start site. Aspects of this "regulatory code" are
      essential for the immune response. These results suggest that immunity regulatory
      DNAs contain constrained organizational features, which may be a general property
      of eukaryotic enhancers.

PMID- 14731392
TI  - Selective recognition of acetylated histones by bromodomain proteins visualized
      in living cells.
AB  - Acetylation and other modifications on histones comprise histone codes that
      govern transcriptional regulatory processes in chromatin. Yet little is known how
      different histone codes are translated and put into action. Using fluorescence
      resonance energy transfer, we show that bromodomain-containing proteins recognize
      different patterns of acetylated histones in intact nuclei of living cells. The
      bromodomain protein Brd2 selectively interacted with acetylated lysine 12 on
      histone H4, whereas TAF(II)250 and PCAF recognized H3 and other acetylated
      histones, indicating fine specificity of histone recognition by different
      bromodomains. This hierarchy of interactions was also seen in direct peptide
      binding assays. Interaction with acetylated histone was essential for Brd2 to
      amplify transcription. Moreover association of Brd2, but not other bromodomain
      proteins, with acetylated chromatin persisted on chromosomes during mitosis. Thus
      the recognition of histone acetylation code by bromodomains is selective, is
      involved in transcription, and potentially conveys transcriptional memory across
      cell divisions.

PMID- 14731393
TI  - Structure of a ternary transcription activation complex.
AB  - The cI protein of bacteriophage lambda (lambdacI) activates transcription by
      binding a DNA operator just upstream of the promoter and interacting with the RNA
      polymerase sigma subunit domain 4 (sigma(4)). We determined the crystal structure
      of the lambdacI/sigma(4)/DNA ternary complex at 2.3 A resolution. There are no
      conformational changes in either protein, which interact through an extremely
      small interface involving at most 6 amino acid residues. The interactions of the
      two proteins stabilize the binding of each protein to the DNA. The results
      provide insight into how activators can operate through a simple cooperative
      binding mechanism but affect different steps of the transcription initiation
      process.

PMID- 14731394
TI  - Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase
      on heat shock genes.
AB  - Positive transcription elongation factor b (P-TEFb) is a kinase that
      phosphorylates the carboxyl-terminal domain (CTD) of RNA Polymerase II (Pol II).
      Here, we show that flavopiridol, a highly specific P-TEFb kinase inhibitor,
      dramatically reduces the global levels of Ser2--but not Ser5--phosphorylated CTD
      at actively transcribed loci on Drosophila polytene chromosomes under both normal
      and heat shocked conditions. Brief treatment of Drosophila cells with
      flavopiridol leads to a reduction in the accumulation of induced hsp70 and hsp26
      RNAs. Surprisingly, the density of transcribing Pol II and Pol II progression
      through hsp70 in vivo are nearly normal in flavopiridol-treated cells. The major
      defect in expression is at the level of 3' end processing. A similar but more
      modest 3' processing defect was also observed for hsp26. We propose that P-TEFb
      phosphorylation of Pol II CTD coordinates transcription elongation with 3' end
      processing, and failure to do so leads to rapid RNA degradation.

PMID- 14731395
TI  - Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain
      couples transcription and 3' end processing.
AB  - The largest subunit of RNA polymerase II contains a unique C-terminal domain
      important for coupling of transcription and mRNA processing. This domain consists
      of a repeated heptameric sequence (YSPTSPS) phosphorylated at serines 2 and 5.
      Serine 5 is phosphorylated during initiation and recruits capping enzyme. Serine
      2 is phosphorylated during elongation by the Ctk1 kinase, a protein similar to
      mammalian Cdk9/P-TEFb. Chromatin immunoprecipitation was used to map positions of
      transcription elongation and mRNA processing factors in strains lacking Ctk1.
      Ctk1 is not required for association of elongation factors with transcribing
      polymerase. However, in ctk1Delta strains, the recruitment of polyadenylation
      factors to 3' regions of genes is disrupted and changes in 3' ends are seen.
      Therefore, Serine 2 phosphorylation by Ctk1 recruits factors for
      cotranscriptional 3' end processing in vivo.

PMID- 14731396
TI  - Structure and mechanism of mRNA cap (guanine-N7) methyltransferase.
AB  - A suite of crystal structures is reported for a cellular mRNA cap (guanine-N7)
      methyltransferase in complex with AdoMet, AdoHcy, and the cap guanylate.
      Superposition of ligand complexes suggests an in-line mechanism of methyl
      transfer, albeit without direct contacts between the enzyme and either the N7
      atom of guanine (the attacking nucleophile), the methyl carbon of AdoMet, or the
      sulfur of AdoMet/AdoHcy (the leaving group). The structures indicate that
      catalysis of cap N7 methylation is accomplished by optimizing proximity and
      orientation of the substrates, assisted by a favorable electrostatic environment.
      The enzyme-ligand structures, together with new mutational data, fully account
      for the biochemical specificity of the cap guanine-N7 methylation reaction, an
      essential and defining step of eukaryotic mRNA synthesis.

PMID- 14731397
TI  - Autoregulation of polypyrimidine tract binding protein by alternative splicing
      leading to nonsense-mediated decay.
AB  - Polypyrimdine tract binding protein (PTB) is a regulator of alternative splicing,
      mRNA 3' end formation, mRNA stability and localization, and IRES-mediated
      translation. Transient overexpression of PTB can influence alternative splicing,
      sometimes resulting in nonphysiological splicing patterns. Here, we show that
      alternative skipping of PTB exon 11 leads to an mRNA that is removed by NMD and
      that this pathway consumes at least 20% of the PTB mRNA in HeLa cells. We also
      show that exon 11 skipping is itself promoted by PTB in a negative feedback loop.
      This autoregulation may serve both to prevent disruptively high levels of PTB
      expression and to restore nuclear levels when PTB is mobilized to the cytoplasm.
      Our findings suggest that alternative splicing can act not only to generate
      protein isoform diversity but also to quantitatively control gene expression and
      complement recent bioinformatic analyses, indicating a high prevalence of human
      alternative splicing leading to NMD.

PMID- 14731398
TI  - Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein
      RHAU.
AB  - The AU-rich element (ARE) in the 3' untranslated region of unstable mRNAs mediate
      their rapid degradation. ARE binding proteins (AUBPs) have been described that
      either stabilize or otherwise degrade ARE-mRNAs by recruiting the exosome, a
      complex of 3'-to-5' exoribonucleases. We have identified RHAU, a putative DExH
      RNA helicase that was isolated in association with the ARE of urokinase
      plasminogen activator mRNA (ARE(uPA)). RHAU physically interacts with the
      deadenylase PARN and the human exosome and enhances the deadenylation and decay
      of ARE(uPA)-mRNAs. An alternatively spliced isoform of RHAU that localized to the
      cytoplasm had a more pronounced effect on ARE(uPA)-mRNA destabilization than full
      length RHAU. Furthermore, the ATPase activity of RHAU is essential for its mRNA
      destabilizing function. ARE(uPA)-mRNA recognition by RHAU may be mediated through
      its RNA-dependent interaction with the AUBPs HuR and NFAR1. A model is presented
      to describe the action of RHAU in ARE(uPA)-directed mRNA turnover.

PMID- 14731399
TI  - Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: the
      universally conserved residues G693 and C795 regulate P-site RNA binding.
AB  - The crystal structures of the universal translation-initiation inhibitors edeine
      and pactamycin bound to ribosomal 30S subunit have revealed that edeine induces
      base pairing of G693:C795, residues that constitute the pactamycin binding site.
      Here, we show that base pair formation by addition of edeine inhibits tRNA
      binding to the P site by preventing codon-anticodon interaction and that addition
      of pactamycin, which rebreaks the base pair, can relieve this inhibition. In
      addition, edeine induces translational misreading in the A site, at levels
      comparable to those induced by the classic misreading antibiotic streptomycin.
      Binding of pactamycin between residues G693 and C795 strongly inhibits
      translocation with a surprising tRNA specificity but has no effect on translation
      initiation, suggesting that reclassification of this antibiotic is necessary.
      Collectively, these results suggest that the universally conserved G693:C795
      residues regulate tRNA binding at the P site of the ribosome and influence
      translocation efficiency.

PMID- 14731400
TI  - Contrasting functions of calreticulin and calnexin in glycoprotein folding and ER
      quality control.
AB  - Calreticulin and calnexin are homologous lectins that serve as molecular
      chaperones for glycoproteins in the endoplasmic reticulum of eukaryotic cells.
      Here we show that calreticulin depletion specifically accelerates the maturation
      of cellular and viral glycoproteins with a modest decrease in folding efficiency.
      Calnexin depletion prevents proper maturation of some proteins such as influenza
      hemagglutinin but does not interfere appreciably with the maturation of several
      others. A dramatic loss of stringency in the ER quality control with transport at
      the cell surface of misfolded glycoprotein conformers is only observed when
      substrate access to both calreticulin and calnexin is prevented. Although not
      fully interchangeable during assistance of glycoprotein folding, calreticulin and
      calnexin may work, independently, as efficient and crucial factors for retention
      in the ER of nonnative polypeptides.

PMID- 14731401
TI  - Cell cycle-regulated recognition of the destruction box of cyclin B by the APC/C
      in Xenopus egg extracts.
AB  - Substrates for mitotic proteolysis such as cyclin B have a 9 residue destruction
      motif, the destruction box (D-box). To identify the receptor that specifically
      binds the D-box, we used affinity chromatography with immobilized D-box matrices.
      We find that the APC/C from Xenopus egg extracts binds to the D-box of cyclin B,
      whereas Fizzy (Cdc20) does not. Mutations in the D-box abolished this
      interaction. We show that this binding is regulated in the cell cycle, such that
      the APC/C from egg extracts in interphase does not bind to the D-box matrix. Our
      results suggest that the APC/C forms a stable interaction with the D-box of its
      substrates in a cell cycle-dependent manner.

PMID- 14731403
TI  - The regulation of endocytosis: identifying dynamin's binding partners.
AB  - Dynamin is a large GTPase implicated in controlling the initial stages of
      endocytosis. Its mechanism of action remains uncertain, but it is expected to
      interact cyclically with components of the endocytic machinery. Dynamin binds to
      a number of different macromolecules, including microtubules, SH3-domain
      containing proteins, and acidic phospholipids. We interpret these findings in
      terms of a cooperative interaction between dynamin and components of coated and
      non-coated pits.

PMID- 14731402
TI  - A mechanism for Wnt coreceptor activation.
AB  - LDL receptor related proteins 5 and 6 (LRP5/6) and their Drosophila homolog Arrow
      are single-span transmembrane proteins essential for Wnt/beta-catenin signaling,
      likely via acting as Wnt coreceptors. How Wnt activates LRP5/6/Arrow to initiate
      signal transduction is not well defined. Here we show that a PPPSP motif, which
      is reiterated five times in the LRP5/6/Arrow intracellular domain, is necessary
      and sufficient to trigger Wnt/beta-catenin signaling. A single PPPSP motif, upon
      transfer to the LDL receptor, fully activates the Wnt pathway, inducing complete
      axis duplication in Xenopus and TCF/beta-catenin-responsive transcription in
      human cells. We further show that Wnt signal-ing stimulates, and requires,
      phosphorylation of the PPPSP motif, which creates an inducible docking site for
      Axin, a scaffolding protein controlling beta-catenin stability. Our study
      identifies a critical signaling module and a key phosphorylation-dependent
      activation step of the Wnt receptor complex and reveals a unifying logic for
      transmembrane signaling by Wnts, growth factors, and cytokines.

PMID- 14731404
TI  - The microtubule lattice--20 years on.
AB  - In 1974, optical diffraction and image analysis indicated that tubulin dimers in
      the cylindrically complete A-tubule of flagellar doublet microtubules are
      arranged with helical symmetry, while those in the incomplete B-tubule associate
      differently. Recently, electron micrographs of reassembled brain microtubules
      decorated with kinesin heads have shown that the tubulin dimers there are
      arranged as in the B-tubule. The lack of symmetry of microtubules assembled in
      vitro prompts Linda Amos to speculate here that the assembly process in vitro may
      differ from that occurring in the cell.

PMID- 14731405
TI  - Getting the actin filaments straight: nucleation-release or treadmilling?
AB  - The dynamic turnover of actin filaments plays a central role in the locomotion of
      metazoan cells. Based on results obtained with actin labelled with a caged
      fluorescent probe, Theriot and Mitchison proposed a 'nucleation-release' model
      for the fast-moving fish keratocyte, which predicts the existence of short non
      oriented filaments in the motile lamellipodium. More recent structural data on
      keratocyte cytoskeletons do not support this model, but are consistent with the
      treadmilling of long actin filaments of graded length. Taken together with
      Theriot and Mitchison's demonstration that the cytoskeleton remains stationary
      relative to the substrate in the moving keratocyte, the structural data raise the
      possibility that a lateral flow of filaments plays a role in lamellipodia
      motility.

PMID- 14731406
TI  - Neglected opportunities in apoptosis research.
AB  - Interest in apoptosis is currently growing rapidly, and previous articles in this
      series in TCB have described a number of recent advances in the field. Certain
      aspects of the process, however, have been relatively neglected. In this article,
      John Kerr draws attention to some of them, with the hope that he may indicate
      potentially productive areas for future research.

PMID- 14731413
TI  - NuMA: a protein involved in nuclear structure, spindle assembly, and nuclear re
      formation.
AB  - The abundant coiled-coil protein NuMA is located in the nucleus during
      interphase, but when the nuclear envelope disassembles in prometaphase it rapidly
      redistributes to the developing spindle poles. Microinjection of antibodies to
      NuMA at or before metaphase can block spindle assembly or cause spindle collapse,
      indicating a role for NuMA in spindle function. NuMA must also play a key role in
      telophase, as NuMA antibodies or truncations of NuMA cause aberrant nuclear
      reassembly despite apparently normal chromosome segregation. Consistent with a
      structural role for NuMA in the nucleus, immunoelectron microscopy reveals NuMA
      to be a component of nuclear filaments.

PMID- 14731414
TI  - SNAPs and NSF: general members of the fusion apparatus.
AB  - The proteins NSF and SNAPs are known to participate in several intracellular
      fusion events, but their exact functions in the fusion process are unclear.
      Molecular studies have now shown that the ability of NSF to hydrolyse ATP is
      essential for membrane fusion and that this activity is regulated by SNAPs. This
      article reviews recent work on NSF and SNAPs, and speculates about how they
      interact with each other and SNAREs to promote membrane fusion.

PMID- 14731415
TI  - Approaches to studying cell adhesion molecules in angiogenesis.
AB  - Capillaries provide a vast interface between the blood and the tissues that is
      crucial for regulating nutrient delivery, blood coagulation and transmigration of
      leukocytes to sites of infection. The growth of new capillaries from pre-existing
      vessels (angiogenesis) is essential for normal embryogenesis and growth, but also
      occurs in the development of many diseases. Although relatively little is known
      about endothelial cell biology, progress is nevertheless being made towards
      understanding angiogenesis, and several laboratories have begun to identify cell
      adhesion molecules that may be required for the growth of microvessels.

PMID- 14731416
TI  - The control of apoptosis in Drosophila.
AB  - Although several genes involved in apoptosis have been identified recently, the
      mechanisms that regulate and execute this process are still not fully understood.
      Drosophila is providing powerful new approaches for studying both the signalling
      pathways that activate apoptosis, and the components of the basic cell death
      programme. Here, we summarize progress in understanding how distinct signals
      influence the death of particular cells in Drosophila, and then review recent
      results that suggest these act through a single pathway in which the reaper gene
      product plays a central role.

PMID- 14731417
TI  - Regulation by ADP-ribosylation.

PMID- 14731421
TI  - From laminin to lamin: regulation of tissue-specific gene expression by the ECM.
AB  - Mammary epithelial cells need a laminin-rich extracellular matrix (ECM) to
      achieve a functionally differentiated phenotype that includes secretion of milk
      specific proteins such as beta-casein. There is good evidence that ECM-induced
      expression of beta-casein involves an 'ECM-response element' in the promoter of
      the casein gene that is activated by integrin-mediated signalling. This article
      proposes that ECM-induced structural changes in the cytoskeleton, histone
      organization and the nuclear matrix contribute to this tissue-specific gene
      expression.

PMID- 14731422
TI  - The nuclear GTPase cycle: promoting peripheralization?
AB  - Numerous Ras-like GTPases function as molecular switches in the cytoplasm, but
      only one has been identified in the nucleus. This nuclear GTPase and its
      homologues are known in both yeasts and higher organisms and in all cases they
      are regulated by guanine-nucleotide-exchange factors. The 'nuclear GTPase cycle'
      created by these components is implicated in mRNA transport from and protein
      import to the nucleus, as well as in DNA replication, RNA processing and the
      regulation of the cell cycle. In this article, Alan Tartakoff and Roger Schneiter
      propose that this GTPase cycle regulates dispersive functions in the nucleoplasm,
      an idea that explains many of the observed effects of disrupting the cycle.

PMID- 14731423
TI  - The bulk-flow hypothesis: not quite the end.

PMID- 14731424
TI  - It's important to concentrate.

PMID- 14731425
TI  - Beyond bulk flow.

PMID- 14731429
TI  - The role of DNA fragmentation in apoptosis.
AB  - The formation of distinct DNA fragments of oligonucleosomal size (180-200 bp
      lengths) is a biochemical hallmark of apoptosis in many cells. Recent
      observations also suggest large DNA fragments and even single-strand cleavage
      events occur during cell death. These observations have raised many questions.
      What are the types of DNA cleavage observed during apoptosis? What are the
      nucleases involved? And what is the role of these nucleolytic events in
      apoptosis?

PMID- 14731430
TI  - The relevance of apoptosis to AIDS pathogenesis.
AB  - Several recent experimental findings support the hypothesis that apoptosis
      induced by human immune deficiency virus (HIV) is important in the pathogenesis
      of acquired immune deficiency syndrome (AIDS). Thus, one potential therapeutic
      strategy against AIDS may be to block the HIV-mediated apoptosis signal
      transduction pathway. Induction of apoptosis by HIV infection may prove a useful
      paradigm for the pathogenesis of a wide range of diseases that involve cell
      depletion and tissue atrophy.

PMID- 14731431
TI  - The cellular responses to DNA damage.
AB  - The ability to survive spontaneous and induced DNA damage, and to minimize the
      number of heritable mutations that this causes, is essential to the maintenance
      of genome integrity for all organisms. Early studies on model eukaryotes focused
      on genes acting in defined DNA repair pathways. More recent work with the budding
      and fission yeasts and mammalian cells has started to integrate the DNA damage
      response with cell physiology and the cell cycle.

PMID- 14731434
TI  - Cosmetic assessment of breast-conserving surgery for primary breast cancer.
AB  - The goals of breast-conserving treatment are to achieve local control and
      survival rates equivalent to mastectomy and to preserve breast cosmetic
      appearance. This paper specifically addresses the different ways of cosmetic
      assessment by the observer (subjective and objective assessments) and by the
      patient (self-assessment), and the factors which influence the cosmetic outcome,
      based on a review of the current literature.

PMID- 14731435
TI  - Nipple aspirate fluid in relation to breast cancer.
AB  - Samples of breast ductal fluid can be obtained by nipple aspiration. Such samples
      may contain a variety of exfoliated or shed cells and display a distinctive
      biochemical profile reflecting the microenvironment of the ductal-alveolar system
      of the breast. Study of nipple aspirates may, therefore, shed light on the
      biology of breast cancer. This review summarizes the more important aspects of
      published data and explores potential avenues for future study with particular
      regard to molecular-biological approaches.

PMID- 14731436
TI  - Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus
      extract: results of a placebo-controlled double-blind study.
AB  - In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex
      agnus castus extract-containing solution (VACS) was investigated in patients
      suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in
      the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30
      drops/day), the intensity of mastalgia was recorded once per cycle using a visual
      analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain
      intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6
      mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were
      significantly greater than those with placebo (p=0.018; p=0.006). After three
      cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a
      reduction of 'borderline significance' (p=0.064) on statistical testing compared
      with placebo (25.7 mm). There was no difference in the frequency of adverse
      events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and
      was well tolerated and further evaluation of this agent in the treatment of
      cyclical mastalgia is warranted.

PMID- 14731437
TI  - Doctors' participation in randomized trials of adjuvant systemic therapy in
      breast cancer: how does it relate to their recommendations for standard therapy
      in breast cancer?
AB  - A cross-sectional survey of all medical and radiation oncologists in Australia
      was undertaken, plus surgeons listed as participants of the ANZ Breast Cancer
      Trials Group, to examine whether doctors' participation in randomized trials of
      adjuvant systemic therapy for breast cancer, is associated with their
      recommendations for adjuvant therapy in two clinical scenarios. Two-hundred and
      sixty-nine questionnaires were returned (response rate 71%). Fifty-six per cent
      of respondents, were participating in current adjuvant systemic therapy trials.
      Radiation oncologists were significantly more likely than surgeons or medical
      oncologists to recommend radiotherapy, while medical oncologists and surgeons
      were significantly more likely than radiation oncologists to recommend
      chemotherapy, in both clinical scenarios. In a multivariate analysis adjusting
      for the differences between specialist groups, respondents recommending
      chemotherapy were more likely to be high accruers to clinical trials (OR 3.6, 95%
      CI 0.93 to 13.9, P=0.08) in scenario 1, or participants of a breast cancer trials
      organization (OR 3.1, 95% CI 1.6 to 5.9, P=0.001) in scenario 2. Some of the
      variation in adjuvant systemic therapy recommendations is associated with
      participation in adjuvant systemic therapy trials. However, this study is unable
      to determine if trial participation influences opinions about adjuvant therapy,
      or opinions influence trial participation.

PMID- 14731438
TI  - Ultrasound findings in pure invasive lobular carcinoma of the breast: comparison
      with matched cases of invasive ductal carcinoma of the breast.
AB  - Pure invasive lobular carcinoma is more difficult to diagnose clinically and
      mammographically than other invasive breast carcinomas. Our objective was to
      document the ultrasound appearances of pure invasive lobular carcinoma, to
      determine whether there were any specific features when compared to similar cases
      of invasive ductal carcinoma, and to compare the sensitivity of ultrasound with
      mammography in the diagnosis of invasive lobular carcinoma. We report on 23 cases
      of invasive lobular carcinoma who were matched for age and presentation with
      cases of invasive ductal carcinoma. High frequency ultrasound detected lesions in
      22 cases of invasive lobular carcinoma and all had features highly suggestive of
      malignancy. Twenty-one of 23 cases of invasive ductal carcinoma also had
      malignant features. At mammography, six cases of invasive lobular carcinoma were
      not detected. Ultrasound is as specific for identifying invasive lobular
      carcinoma as it is for invasive ductal carcinoma. Ultrasound was more sensitive
      than mammography for diagnosing invasive lobular carcinoma.

PMID- 14731439
TI  - Is mastectomy overtreatment for Paget's disease of the nipple?
AB  - The standard local management for Paget's disease of the nipple is currently
      mastectomy although this may well represent overtreatment. The place of breast
      conserving surgery is somewhat uncertain. We have reviewed the casenotes of 146
      patients with Paget's disease of the nipple, and compared the mortality and
      recurrence rates between 74 women who had undergone mastectomy and 31 women who
      had breast conserving surgery. There was no significant difference in either
      local or overall treatment failure rates between these two treatment groups. We
      conclude that breast conserving treatment maybe an appropriate alternative to
      mastectomy for the management of Paget's disease, where clear margins of excision
      can be achieved. However, a randomized prospective study is needed to confirm
      this.

PMID- 14731440
TI  - Management of high-risk node-positive breast cancer by standard-dose chemotherapy
      and loco-regional radiotherapy.
AB  - One-hundred, thirty-six women, aged up to 76 years, with high-risk breast cancer
      were treated with postoperative radiotherapy and 9 cycles of adjuvant
      chemotherapy in standard doses. Treatment-related toxicity was mild. At a median
      follow-up of 7.3 years, 39.6% are disease-free. At 5 and 10 years overall
      survival was 55% and 34% respectively; disease-free survival was 39% and 33%
      respectively. Eighteen patients (13.2%) developed loco-regional recurrence, which
      was uncontrolled in four. When compared to series treated with adjuvant
      chemotherapy, but without radiotherapy, there are apparent survival gains of 10
      15% at 5 and 10 years. These results in both pre- and post-menopausal patients
      compare favourably with results of high-dose chemotherapy and stem-cell rescue in
      much more highly selected patients.

PMID- 14731441
TI  - Long-term survival following postmastectomy locoregional recurrence of breast
      cancer.
AB  - Only a few reports describe long-term survivors following locoregional recurrence
      of breast cancer after mastectomy. We analyzed 145 patients who were treated for
      an isolated postmastectomy breast cancer recurrence at our department between
      1979 and 1992. All patients were free from distant metastases at the time of
      recurrence. Nineteen of these patients remained free from distant metastases
      after a follow-up of more than 10 years following recurrence. Clinical and
      histopathological characteristics of these 19 patients were analyzed. Primary
      tumors were small with almost all being T1 or T2 primaries. The majority of
      survivors had negative axillary node status (16/19 [84%]). Locoregional
      recurrences were mainly chest wall recurrences (16/19 [84%]) and all recurrences
      were smaller than 5 cm (19/19). Only 7 patients showed a typical scar recurrence.
      Sixteen patients had a single recurrent nodule. Early recurrences (<1 year after
      mastectomy) were rare (n=2). Treatment of recurrence consisted of tumor excision
      in all cases followed by radiotherapy in 16 patients (including 6 patients who
      had undergone elective irradiation following mastectomy), hormonal therapy in 6
      and chemotherapy in 1 case. In all patients local control at the recurrence site
      was achieved. Cure after postmastectomy recurrence seems possible in a subgroup
      of patients (small primary tumor with negative axilla, small and solitary chest
      wall recurrence) provided adequate therapy is prescribed. Treatment of these
      patients should not be regarded as palliative therapy.

PMID- 14731442
TI  - Costs of breast cancer treatment in the United Kingdom.
AB  - Breast cancer is a major source of mortality and morbidity to women in the UK. In
      this paper we estimate the costs of treating breast cancer using random samples
      of secondary and primary care records. We estimate the average cost per case of
      breast cancer to be pound 7247 which gives a total cost of pound 243 million per
      annum for the whole of the UK.

PMID- 14731443
TI  - Telomerase activity in the human breast.
AB  - Telomerase is a ribonucleoprotein enzyme which appears to play an important role
      in carcinogenesis. Telomerase reactivation seems to be associated with
      immortalization and malignancy. Using a PCR-based assay, we examined telomerase
      activity in 50 breast tissue specimens, prospectively obtained from 37 women
      undergoing elective breast surgery. The specimens examined included normal breast
      (n=13), benign breast lesions (n=5), ductal carcinoma in situ (n=8) and
      infiltrating ductal carcinoma (n=24). All normal breast, benign breast and DCIS
      specimens lacked telomerase activity. Sixteen (67%) of 24 infiltrating
      carcinomas. In infiltrating ductal cancer, there was a statistically significant
      association between telomerase activity and nodal metastasis. The present results
      indicate that telomerase activity is associated with acquisition of invasive
      malignancy in the human breast and may have a role in complementing
      cytopathological diagnosis. Telomerase activity as a prognostic marker should be
      included in future validation studies. In DCIS, telomerase activity may be a late
      event associated with invasion of the basement membrane.

PMID- 14731444
TI  - Biogenesis of phagolysosomes: the 'kiss and run' hypothesis.
AB  - Particles such as microorganisms that are taken up by the cell into phagosomes
      are usually ultimately degraded in phagolysosomes. However, despite its
      importance, phagolysosome biogenesis is poorly understood. This article presents
      a model for phagosome maturation into phagolysosomes that involves multiple
      transient fusion-fission interactions of phagosomes with endocytic organelles via
      a fusion-pore-like structure. This dynamic process may be modulated by the
      sequential appearance and disappearance of key phagosome proteins.

PMID- 14731445
TI  - Guilty by insolubility--does a protein's detergent insolubility reflect a
      caveolar location?
AB  - Several recent papers have described a simple approach to isolate caveolae and
      proteins involved in apical sorting in epithelial cells that is based on their
      detergent insolubility. These publications have excited such diverse fields of
      cell biology as intracellular protein transport, signal transduction and, in
      particular, research into caveolae. In this article, Kurzchalia, Hartmann and
      Dupree argue that a more critical evaluation of this detergent insolubility is
      needed before a subcellular location or function can be ascribed to a protein.

PMID- 14731446
TI  - The importance of importin.
AB  - The accumulation of karyophilic proteins in the nucleus requires cytoplasmic
      factors. Cell-free systems that reconstitute nuclear protein import have been
      used to identify several of these factors and to define the biochemical
      requirements for the import process. Recently, one factor has been purified and
      cloned from Xenopus and identified as a homologue of the 'suppressor of RNA
      polymerase l' (SRP1) gene originally described in yeast. This factor belongs to a
      closely related group of proteins that may share similar functions in nuclear
      protein transport.

PMID- 14731447
TI  - A Ran-binding motif in nuclear pore proteins.

PMID- 14731448
TI  - Cytoplasmic or cytosolic--a tale of tails.

PMID- 14731449
TI  - In search of a function for centrins.
AB  - Spindle pole bodies, basal bodies and centrosomes are morphologically quite
      different structures that nevertheless perform similar microtubule-organizing
      functions in diverse cell types. The recent discoveries that both centrins and
      gamma-tubulin are common components of these structures suggest a molecular basis
      for their common functions. The role of centrins is just beginning to be
      investigated. These filament-associated proteins bind Ca2+. The filaments
      contract at least in certain circumstances by an ATP-independent mechanism.
      However, yeast centrin is clearly involved in the duplication of the spindle pole
      body. A common molecular mechanism may underlie these two apparently different
      functions.

PMID- 14731450
TI  - Roles for mannose-6-phosphate receptors in lysosomal enzyme sorting, IGF-II
      binding and clathrin-coat assembly.
AB  - Two related transmembrane proteins in mammalian cells bind the mannose 6
      phosphate recognition marker present on all soluble lysosomal hydrolases. Recent
      studies of cells that express only one or neither of these proteins have shed
      light not only on their function in directing lysosomal enzymes into the
      endocytic pathway but also on their critical role in transport vesicle formation
      in the trans Golgi network. One of these proteins also binds insulin-like growth
      factor II (IGF-II) and may be an important part of the IGF-dependent system that
      regulates development.

PMID- 14731451
TI  - Partner proteins determine multiple functions of Hsp70.
AB  - The 70 kDa heat shock proteins (Hsp70s) are ubiquitous molecular chaperones that
      are best known for their participation in protein folding. However, evidence is
      accumulating that Hsp70s perform several other cellular functions in cooperation
      with specific soluble or membrane-bound partner proteins. While the basic
      function of Hsp70s is explained by their ability to bind unfolded polypeptide
      segments, the partner proteins appear to customize them for specific roles such
      as involvement in protein traffic and folding, translocation of preproteins
      across membranes, and gene regulation.

PMID- 14731456
TI  - Breast cancer screening sensitivity in the NHSBSP: recent results and
      implications.
AB  - This paper reviews the lessons learnt from the UK National Health Service Breast
      Screening programme.

PMID- 14731457
TI  - Role of positron emission tomography in the management of breast cancer.
AB  - Positron emission tomography (PET) is an imaging modality that utilises tracers
      based on biologically important compounds and can be used to study in vivo tissue
      function. This article reviews the current status of PET imaging in breast
      disease. The positron emitting glucose analogue 18F-FDG is used to image tissue
      glycolysis and has been extensively evaluated. Studies have shown that 18F-FDG
      PET has a high sensitivity and specificity for the detection of primary breast
      cancers, however its use is not superior that of conventional imaging modalities.
      Considerable interest is now focussing on the application of PET to non
      invasively determine the lymph node status of patients with breast cancer and to
      predict and evaluate tumour response to chemotherapy. Relatively low cost gamma
      camera systems are now available that are capable of PET imaging, and thus it may
      therefore be possible to perform PET imaging in the majority of hospitals.

PMID- 14731458
TI  - Conservative methods for breast cancer of small size: the experience of the
      National Cancer Institute, Milan (1973-1998).
AB  - Late results of the Milan breast conservation studies are presented. Conclusions
      based on the Milan experience can be drawn.

PMID- 14731459
TI  - Breast conservative surgery: is it appropriate for locally advanced breast cancer
      following downstaging by neoadjuvant chemotherapy? A pathological assessment.
AB  - The application of breast conserving surgery to down-staged cases with locally
      advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a
      controversial issue with a variable incidence of locoregional failures. In this
      study, the response of LABC to NACT was assessed pathologically and the eligible
      candidates for breast conserving surgery were identified retrospectively. The
      efficacy of preoperative clinical examination and mammography in detecting these
      pathological changes were also evaluated. The study included 41 LABC cases. They
      received NACT (FAC) and were then subjected to a mastectomy. The cases were
      examined clinically and by mammography before starting treatment and immediately
      before surgery. Residual tumours in the mastectomy specimens were correlated with
      the pretreatment and preoperative clinical and mammographic findings in order to
      assess the efficacy of these tools for detection of NACT-induced changes. After 3
      cycles of NACT, 78% of women showed an objective response. However, only 25% of
      them would have been eligible for breast conserving surgery. The remaining
      responders had an increased incidence of either multifocality and or peritumoural
      in situ carcinoma. Both clinical examination and mammography were inadequate for
      detection of these chemotherapy-induced changes and hence for selecting suitable
      candidates for breast conservation. This study has shown that tumour regression
      by NACT is probably induced by a process of tumour segmentation and is associated
      with an increased incidence of ductal in situ lesions in the original tumour
      bearing area.

PMID- 14731460
TI  - Is centralized histopathology review necessary for screen-detected breast
      lesions?
AB  - To address quality requirements for breast pathology in the Australian screening
      programme, one breast cancer Screening and Assessment Service initiated a process
      of central pathologic review of all lesions detected through the service. The aim
      of this study was to measure concordance between the initial and review
      pathology, and to assess the merit of routine review. Concordance was measured by
      observed agreement and the kappa statistic for 267 women with 273 lesions.
      Concordance was excellent for the four classification schemes examined, good for
      the identification of benign lesions and hyperplasia, and excellent for the
      identification of DCIS or invasive carcinoma. For the sub-categorization of
      hyperplasias and invasive carcinomas concordance was good, but was poor for the
      sub-typing of DCIS. Initial and review concordance was acceptable, suggesting
      that disagreement among pathologists may not present a major impediment to the
      provision of dependable diagnoses. Full case review is unnecessary for benign
      lesions or invasive carcinoma, but should be maintained for DCIS and
      hyperplasias.

PMID- 14731461
TI  - Body mass index, height and cumulative menstrual cycles at the time of diagnosis
      are not risk factors for poor outcome in breast cancer.
AB  - Obesity, height and age at menarche have been shown to be risk factors for the
      development of primary breast cancer. However, their prognostic influence on
      breast cancer once it has presented is uncertain. The present study analysed 448
      patients with primary breast cancer to determine whether or not body mass index
      (BMI), height and cumulative menstrual cycles at diagnosis are independent
      prognostic variables. The effects of all three variables on survival time and
      disease free interval were estimated. Of the 448 patients after a median follow
      up of 6 years, 190 (42%) developed recurrence and 162 (36%) had died. Body Mass
      Index and height could be calculated from available data in 403 patients and
      cumulative menstrual cycles in 388 patients. There was no evidence of an effect
      of BMI on survival time (P=0.99; hazard ratio=1.000; 95% Confidence Interval
      0.968-1.034) or disease free interval (P=0.92; hazard ratio=1.002; 95% Confidence
      Interval 0.973-1.031). Similarly, height and cumulative menstrual years did not
      influence outcome in patients with primary breast cancer. However, nodal status
      and tumour size were both significant prognostic factors (P<0.001). The present
      study found no association between Body Mass Index, height and cumulative
      menstrual years and outcome in patients with primary breast cancer.

PMID- 14731462
TI  - Psychological distress associated with waiting for results of diagnostic
      investigations for breast disease.
AB  - This paper presents the results of a multi-method research project investigating
      the psychological distress associated with waiting for results of diagnostic
      investigations in a delayed-results breast clinic. A cohort of 126 women
      completed standardized psychometric instruments to assess anxiety, mood and
      coping over 3 days. Semi-structured interviews were conducted with 20
      respondents. The findings indicate that waiting sustained but did not exacerbate
      psychological distress. Peri-diagnostic anxiety, depression, uncertainty and
      confusion were associated with anxiety levels immediately following triple
      assessment. Women leaving the clinic with low anxiety retained this composure
      throughout the peri-diagnostic period. Those in the moderate and high anxiety
      groups recorded sustained anxiety, depression, uncertainty and confusion, with
      mean scores comparable to and exceeding those reported by psychiatric out
      patients. Coping during the waiting period was typically accomplished by emotion
      focused strategies. Qualitative data suggested the delayed-results clinic
      structure may facilitate psychological preparation for test results.

PMID- 14731463
TI  - Radial scar and carcinoma of the breast: microscopic findings in 32 cases.
AB  - We retrospectively reviewed the microscopic findings in 32 histologically
      confirmed radial scars in 31 women diagnosed in our unit during 1994-1998. The
      median age at diagnosis was 53 years (range 47-63 years). Thirty-one (97%) of 32
      lesions presented as screen detected mammographic abnormalities (28 stellate
      lesions, 2 microcalcifications and only 1 architectural distortion). One lesion
      presented as a palpable breast mass. Stereotactic or ultrasound-guided fine
      needle aspiration cytology (FNAC) was performed in 28 cases. Cytological analysis
      of FNAs revealed malignant cells (C5) in 8 (29%) cases, highly suspicious cells
      (C4) in 3 (11%) cases, atypical benign cells (C3) in 7 (25%) cases and benign
      epithelial cells (C2) in 10 (35%) cases. All non-palpable lesions were surgically
      excised following wire localization. Histological examination of the breast
      specimens (mean weight=16 g) demonstrated, in addition to a radial scar, 6
      invasive carcinomas (2 infiltrating ductal, 2 tubular, 1 mixed ductal/lobular and
      1 secretory carcinoma) and 4 ductal carcinoma in situ lesions (2 high grade, 1
      high grade with micro-invasion and 1 low grade) arising in the radial scar. Of
      the remaining cases the radial scar was associated with atypical epithelial
      hyperplasia in 2 cases and regular epithelial hyperplasia in 17 cases (4 florid
      and 13 mild to moderate). In the 10 cases associated with malignancy, 9 had FNAC
      and was reported as malignant (C5) in 6 (67%) cases, highly suspicious (C4) in 2
      (22%) cases and atypical (C3) in 1 (11%). False positive FNAC (C5) occurred in
      two patients, one of whom presented with pleomorphic microcalcifications
      suggestive of ductal carcinoma in situ. This patient was treated with a wire
      guided segmental mastectomy. All invasive tumours were less than 20 mm in size
      (T1) and of these 4 were grade I and 2 were grade II. Axillary dissection was
      performed in 4 patients none of whom had axillary node metastases. Our study
      demonstrates a significant incidence of malignancy associated with radial scars
      (31%) suggesting that radial scars may be premalignant lesions. This is supported
      by detecting various stages of mammary carcinogenesis (atypical epithelial
      hyperplasia, ductal carcinoma in situ, and early invasive malignancy) in these
      lesions. Fine needle aspiration cytology seems to be unreliable in the diagnosis
      of radial scar associated malignancy (67% sensitivity and 91% specificity).
      Stellate lesions, therefore, should be excised to obtain an histological
      diagnosis regardless of cytological findings. Further studies examining the
      biology of radial scars are required.

PMID- 14731464
TI  - Breast screening uptake rates: does access to Saturday sessions lead to
      improvements?
AB  - Offering women the option of attending for breast screening on Saturday did not
      increase the rate of uptake in a study performed in a city site in Manchester,
      UK.

PMID- 14731465
TI  - Nocardia asteroides: an unusual cause of breast abscess.
AB  - A case of nocardial breast infection is presented and infection by nocardia
      organisms must be considered as a rare differential diagnosis of chronic
      inflammation of the breast.

PMID- 14731466
TI  - Ca2+ channels and signalling in cilia and flagella.
AB  - Ca(2+) plays a key role in the regulation of ciliary and flagellar movement. This
      article focuses on the initial steps of this regulation: how and where Ca(2+)
      enters cilia and flagella to trigger specific changes in axonemal motility. This
      knowledge is fundamental for understanding the sites, molecular targets and
      mechanisms of action of Ca(2+) within the cilium of flagellum.

PMID- 14731467
TI  - Peptide traffic across the ER membrane: TAPs and other conduits.
AB  - Transport of antigenic peptides across the membrane of the endoplasmic reticulum
      (ER) is an essential step in the association of peptide and MHC class I molecules
      for antigen presentation. The genes for the peptide transporter subunits were
      cloned several years ago, but only recently has it been possible to demonstrate
      their activity in vitro, distinct from an alternative peptide import route, and
      to characterize their substrate specificity. In addition, this work has led to
      the discovery of a novel peptide export activity from the mammalian ER.

PMID- 14731468
TI  - Lamin-dependent nuclear envelope reassembly following mitosis: an argument.
AB  - During the division of most eukaryotic cells, the nuclear envelope disassembles
      and subsequently reassembles around the segregated chromosomes to form two new
      nuclei. With the use of cell-free systems, the molecular mechanisms that underlie
      this complicated process are beginning to be studied. The importance of nuclear
      lamins in nuclear envelope reassembly has been controversial for the past five
      years, but recent findings may help to clarify their role. In this article, we
      propose a working model for nuclear envelope reassembly.

PMID- 14731469
TI  - Cracks in the foundation: keratin filaments and genetic disease.
AB  - In the past three years, defects in the genes that encode intermediate filament
      (IF) proteins have been found to be responsible for some inherited skin diseases,
      and others have been implicated in certain motor neuron diseases and
      cardiomyopathies. This article reviews how knowledge of IF structure led to the
      discovery of genetic disorders of IFs, and how the clinical manifestations of
      these diseases have confirmed the notion that IFs provide the mechanical strength
      of cells.

PMID- 14731470
TI  - Lymphocyte recirculation and homing: roles of adhesion molecules and
      chemoattractants.
AB  - Lymphocyte migration from high endothelial venules into lymphoid organs is
      mediated by a sequence of interactions between cell adhesion molecules on
      lymphocytes and those on the vascular endothelial cells that line the vessels.
      recent studies suggest that the so-called lymphocyte homing receptors and
      vascular addressins regulate the first stages of this process, that of binding of
      lymphocytes from flowing blood. The subsequent crawling of lymphocytes over the
      endothelial cell surface and migration across the vessel wall (diapedesis) are
      regulated independently of initial binding. These latter stages are thought to be
      mediated by functional activation of integrins on the lymphocyte by
      chemoattractants located in the vessel wall.

PMID- 14731471
TI  - Salicylic acid, active oxygen species and systemic acquired resistance in plants.
AB  - Infection of plants, particularly by a necrotizing pathogen, usually induces a
      long-lasting, broad-based, systemic resistance to secondary pathogen attack. Many
      studies implicate salicylic acid as an essential signal in the development of
      such systemic acquired resistance in several plant species. Salicylic acid
      appears to mediate plant defence by binding to and inhibiting catalase, thus
      increasing the concentration of H(2)O(2) and other active oxygen species. Active
      oxygen species may then act as second messengers that induce plant defence gene
      expression, analogous to their activation of gene expression in mammalian cells.

PMID- 14731472
TI  - A game plan for exocytosis.

PMID- 14731478
TI  - Potocytosis, 5'-nucleotidase and transport.

PMID- 14731477
TI  - The nucleation-release model of actin filament dynamics in cell motility.
AB  - The actin cytoskeleton is intimately involved in the motile behaviour of animal
      cells. The structure and dynamic behaviour of actin and its binding proteins have
      been intensively studied in vitro over the past several decades, culminating in
      achievements such as an atomic model of the actin filament. Despite this
      progress, it is not yet clear how the behaviour of these purified proteins in
      vitro relates to the dynamic behaviour of actin inside living, moving cells. Here
      we discuss a new model that relates the known dynamic parameters for pure actin
      to the observed behaviour of actin filaments inside motile cells.

PMID- 14731479
TI  - The endoplasmic reticulum as a protein-folding compartment.
AB  - The lumen of the endoplasmic reticulum (ER) provides a dynamic and efficient
      environment for the folding of proteins destined for secretion and for a variety
      of cellular compartments and membranes. Usually, the folding process begins on
      the nascent chains and is completed minutes or hours later during assembly of
      oligomers. It is assisted by molecular chaperones and folding enzymes, some of
      which are unique to the ER. Quality control and selective degradation systems
      ensure only conformationally mature proteins are transported from the ER.

PMID- 14731480
TI  - Ceramide: a novel second messenger.
AB  - Sphingomyelin used to be considered only as a structural molecule of the outer
      leaflet of the plasma membrane of mammalian cells. However, in the last five
      years it has become clear that sphingomyelin is rapidly degraded and
      resynthesized in a pathway that could function in signal transduction. Indeed, it
      is now known that this pathway plays a role in signal transduction for at least
      one cytokine, tumour necrosis factor alpha. It seems possible that other cell
      surface receptors will also utilize this pathway for signalling.

PMID- 14731481
TI  - Octadecanoid-derived signals in plants.
AB  - Signalling pathways that regulate the expression of plant genes are poorly
      understood. Recent evidence indicates that octadecanoid-derived signals may be
      parts of signalling pathways in plants in which C(18) fatty acids, liberated from
      membranes in response to environmental or developmental cues, are converted to
      intracellular signalling molecules such as jasmoric acid and traumatin. These
      events are analogous to prostaglandin and leukotriene synthesis in animals.

PMID- 14731482
TI  - Keeping track of cell surface receptor.

PMID- 14731483
TI  - A new axis for cell division.

PMID- 14731490
TI  - Dissecting clathrin-coated pits.
AB  - In vitro cell biology has become an effective way to identify molecules
      responsible for membrane traffic. We have used this approach to study the
      assembly and budding of coated pits. So far our system has allowed us to identify
      a high-affinity binding site for the AP2 subunit on the inside surface of plasma
      membranes, determine the AP2 domain that links clathrin lattices to the plasma
      membrane, and purify a molecule that appears to participate in coated-pit
      budding. These discoveries now need to be verified in vivo.

PMID- 14731491
TI  - mRNA translation and turnover: a cellular perspective on their relationship.
AB  - The rate at which a protein is synthesized is influenced by the stability of its
      mRNA and the efficiency of translation. mRNA degradation is associated with
      translation, but the link between these processes is unclear. In this article,
      Alistair Brown discusses this relationship in the light of a model of translation
      that involves three distinct cellular phases: a primary phase in which the
      translation of an mRNA molecule starts before its export from the nucleus is
      complete, a secondary phase that begins when nuclear export is complete and that
      may involve circular polyribosomal complexes, and a terminal phase involving
      residual translation once mRNA degradation is initiated.

PMID- 14731492
TI  - Protein import into chloroplasts.
AB  - The structural complexity of chloroplasts is reflected in their intriguing
      protein-targeting system. Not only must nucleus-encoded proteins be targeted to
      the chloroplast, but also, once inside the chloroplast, these polypeptides must
      be directed to their final destination in one of six intrachloroplastic
      compartments. Although the details of this process remain elusive, many recent
      advances have improved our vantage point for examining this system.

PMID- 14731493
TI  - The oligodendrocyte and its many cellular processes.
AB  - The oligodendrocyte (OL) is increasingly providing a model system for probing
      central issues of cell biology. During development, OL progenitors undergo
      controlled migration, proliferation and differentiation, secrete and respond to a
      number of growth factors, and dramatically change their cellular architecture,
      culminating in the formation of the myelin sheath. This review examines some
      facets of the OL that make it an especially attractive tool for studying many
      basic questions in cell biology.

PMID- 14731494
TI  - The coiled body.
AB  - The coiled body is a nuclear organelle that contains snRNPs involved in splicing,
      the non-snRNP splicing factor U2AF and the nucleolar protein fibrillarin. It is
      highly conserved in evolution and is present in both animal and plant cells. The
      coiled body is a dynamic structure that can undergo regulated cycles of assembly
      and disassembly during interphase and mitosis and it may represent a distinct
      metabolic compartment within the nucleus.

PMID- 14731495
TI  - High-resolution SEM in cell biology.

PMID- 14731497
TI  - Toxin entry: how reversible is the secretory pathway?
AB  - A number of proteins produced by plants and bacteria are extremely toxic to
      eukaryotic cells. Their potency arises from their ability to catalyse the
      modification of crucial cellular components. Only a few toxin molecules are
      required to kill a cell, but to do so they must first reach the cytosol. How such
      proteins are translocated across the target cell membrane is poorly understood,
      but we argue here that some toxins may travel the secretory pathway in reverse,
      passing all the way from the cell surface to the endoplasmic reticulum (ER)
      before entering the cytosol.

PMID- 14731498
TI  - A model of spectrin as a concertina in the erythrocyte membrane skeleton.
AB  - To maintain its distinctive biconcave shape, the erythrocyte has a skeleton
      composed largely of the protein spectrin, which associates closely and
      exclusively with the cell membrane. Although the membrane skeleton forms through
      specific protein-protein interactions of defined stoichiometry, it has a flexible
      structure and organization due to the unusual molecular properties of spectrin.
      Here we describe these properties and propose a model to account for the
      extensibility of spectrin and for its organization in the skeleton.

PMID- 14731499
TI  - The structure of an endocytosis signal.
AB  - The efficient endocytosis of transmembrane receptor proteins requires a signal
      sequence in the cytoplasmic domain of the protein to promote clustering into
      coated pits. Analysis of the clustering of receptors with natural or engineered
      mutations in their cytoplasmic domains implicates an aromatic residue in a
      particular context as the necessary clustering signal. Recent detailed studies of
      mutants have led to computer predictions of a plausible structural motif. These
      predictions have now been elegantly supported by using NMR to determine the
      structure of synthetic peptides. New evidence that this sorting signal performs
      multiple functions suggests that this may not be the whole story.

PMID- 14731500
TI  - Extracellular proteases and embryonic pattern formation.
AB  - At least three genes that play crucial roles in dorsal-ventral patterning of the
      Drosophila embryo appear to encode extracellular proteases. These proteases are
      involved in the generation of localized extracellular ligands for membrane
      receptors. Because the sequences of these gene products closely resemble those of
      mammalian enzymes that have been studied in detail biochemically, it is possible
      to draw on the wealth of information on the biochemical mechanisms that regulate
      protease activity to make inferences about how proteases can be used to generate
      spatial asymmetries within fields of cells.

PMID- 14731502
TI  - Atomic force microscopy for high-resolution imaging in cell biology.

PMID- 14731501
TI  - Presentation of antigenic peptides by MHC class I molecules.
AB  - The basis for the immune response against intracellular pathogens is the
      recognition by cytotoxic T lymphocytes of antigenic peptides derived from
      cytosolic proteins, which are presented on the cell surface by major
      histocompatibility complex (MHC) class I molecules. The understanding of MHC
      class I-restricted peptide presentation has recently improved dramatically with
      the elucidation of the structural basis for the specificity of peptide binding to
      MHC class I molecules and the identification of proteins encoded in the class II
      region of the MHC that are putatively involved in the production of peptides and
      their transport into the endoplasmic reticulum, where they assemble with class I
      molecules.

PMID- 14731508
TI  - Kinesins in the spindle: an update.
AB  - Eukaryotes contain a superfamily of microtubule-based motor proteins comprising
      kinesin and a number of related proteins that are thought to participate in
      various forms of intracellular motility, including cell division and organelle
      transport. The role of various members of the kinesin superfamily in chromosome
      segregation and spindle morphogenesis was described in TCB last year in parts of
      a series on cytoplasmic motor proteins. In this brief update, Helen Epstein and
      Jon Scholey comment on new findings that have improved our understanding of the
      functions of kinesin-related proteins in mitosis and meiosis.

PMID- 14731509
TI  - The role of lipid anchors for small G proteins in membrane trafficking.
AB  - Small GTP-binding proteins of the Ras superfamily play diverse roles in
      intracellular trafficking. In order to perform these functions, the proteins must
      associate with specific donor vesicles and be recycled after fusion of these
      vesicles with their acceptor membrane target. Recent results have identified a
      number of lipid modifications of these proteins, occurring at the N- or C
      termini, that contribute to their membrane binding. Recycling appears, in some
      cases, to be mediated by soluble proteins that bind the lipid-modified tails,
      removing them from the membrane and allowing their reutilization via the cytosol.

PMID- 14731510
TI  - Protein sorting and secretion granule formation in regulated secretory cells.
AB  - Formation of secretion granules in regulated secretory cells involves packaging a
      subject of proteins undergoing intracellular transport into specific vesicular
      carriers that function in stimulus-dependent exocytosis. Recent findings suggest
      that immature granules are a site of passive sorting, involving condensation of
      regulated secretory proteins. Proteins that are not condensed are stored to a
      lesser degree and are enriched in unstimulated, constitutive-like secretion.
      While these observations have helped to distinguish possible mechanisms of
      secretory protein sorting, there are only recent hints about the sorting
      processes that may be required to create the regulated secretory carrier
      membranes.

PMID- 14731511
TI  - Sphingolipid trafficking--sorted out?
AB  - Studies of intracellular membrane traffic have traditionally focused on the
      protein components of membranes, but what about lipids? Recent findings have
      drawn attention to the transport of one type of lipid, the sphingolipids. Their
      unique physical properties may allow them to aggregate into microdomains in
      membranes that concentrate sphingolipids into specific transport pathways. Gerrit
      van Meer and Koert Burger consider here the routes of sphingolipid biosynthesis
      and transport, and the role of proteins in their targeting. The following article
      by Deborah Brown turns the tables to review the evidence suggesting that
      sphingolipid domains are important in specific targeting of GPI-anchored proteins
      to the plasma membrane.

PMID- 14731512
TI  - Interactions between GPI-anchored proteins and membrane lipids.
AB  - Proteins anchored in membranes by glycosylphosphatidylinositol (GPI) are widely
      distributed, but the function of this unusual anchor is a puzzle. Recent evidence
      shows that these proteins can associate with membrane lipids in special ways. One
      function of GPI anchorage may be to allow proteins to interact with specialized
      membrane domains.

PMID- 14731513
TI  - The molten globule intermediate for protein insertion or translocation through
      membranes.
AB  - Insertion of some protein toxins into membranes proceeds through an unfolding
      step. The unfolding trigger can be the low pH in endosomes, exposure to body
      temperature, reduction of disulphide bonds or proteolytic cleavage occurring at
      the membrane surface. The insertion intermediates are not fully unfolded but have
      the features of a 'molten globule state' that is also observed at early stages of
      polypeptide folding. In this article, we review the evidence supporting these
      ideas and speculate about the implications of the molten globule intermediate for
      understanding the general mechanisms of protein insertion and translocation
      across membranes.

PMID- 14731516
TI  - Multimolecular associations of the T-cell antigen receptor.
AB  - T cells are activated when the T-cell receptor for antigen (TCR) interacts with
      an antigenic peptide bound to a major histocompatibility complex (MHC) molecule
      on the surface of another cell. It is often assumed that T-cell activation is
      induced by the crosslinking of TCRs. In this article, Albertus Beyers, Louise
      Spruyt and Alan Williams argue that this mechanism is not generally applicable.
      They hypothesize that the key event in T-cell activation is the formation of
      multimolecular complexes consisting of the TCR and several other polypeptides,
      including CD4 or CD8, CD2, CD5 and the associated tyrosine kinases p59(fyn) and
      p56(lck).

PMID- 14731517
TI  - Positional information in cells and organisms.
AB  - The processes of pattern formation are usually considered to be quite different
      in unicellular and multicellular organisms. The only unifying ideas have been
      very general, such as those concerning regional differences and organization
      along a polar axis. Concepts like induction, fields and gradients have generally
      been applied only to the development of multicellular organisms. Here, Joseph
      Frankel suggests that pattern formation by multicellular organisms evolved in
      their progenitors in response to multiplication of cytoplasmic structural units
      rather than of nuclei. Ciliates provide a living example of complex patterning in
      a compound uninucleate organism.

PMID- 14731518
TI  - Apoptosis: final control point in cell biology.
AB  - The discovery of apoptosis, a widespread and morphologically distinct form of
      physiological cell death, has had an extraordinary impact on cell biology. The
      importance of apoptosis stems from its active nature and its potential for
      controlling biological systems. The growing appreciation of the significance of
      this process has stimulated intense investigation into the molecular mechanisms
      involved and into its fundamental implications for developmental biology,
      immunology and oncology.

PMID- 14731519
TI  - T-cell activation.
AB  - Activation of T lymphocytes results in immediate intracellular biochemical
      changes, including increases in cytosolic Ca(2+) levels, stimulation of protein
      kinase C (PKC) and regulation of protein tyrosine kinases (PTKs). This review
      describes recent advances in the study of the signalling steps downstream of PKC
      and PTKs in T cells. A model is presented in which the GTP-binding protein
      p21(ras) acts as an integrator of the signal transduction pathways controlled by
      the T-cell antigen receptor.

PMID- 14731520
TI  - Cyclophilins: a new family of proteins involved in intracellular folding.
AB  - Proteins of the cyclophilin family display two intriguing properties. On the one
      hand, they are the intracellular receptors for the immunosuppressive drug
      cyclosporin A (CsA); on the other hand, they function in vitro as enzymes that
      catalyse slow steps in protein folding. A dissection of the role of CsA in
      mediating immunosuppression, together with recent studies on the biology of
      cyclophilins in the absence of this ligand, is providing fundamental insight into
      the cellular function of this protein family.

PMID- 14731521
TI  - Checkpoint controls that couple mitosis to completion of DNA replication.
AB  - Cells treated with inhibitors of DNA synthesis do not normally enter mitosis.
      Incompletely replicated DNA apparently activates a regulatory mechanism that
      prevents activation of the mitotic inducer M-phase kinase by controlling the
      dephosphorylation of a critical tyrosine residue in the active site of the
      kinase. The control system may also target a second mitotic inducer, possibly the
      NIMA protein kinase. Unreplicated DNA may be detected and signalled by a complex
      of RCC1, a DNA-binding protein, and Ran, a Ras-related protein. This article
      reviews these recent developments and discusses the possibility that the control
      system also operates in the normal cell cycle, to ensure that mitosis strictly
      follows S phase.

PMID- 14731523
TI  - Chloride channels, Golgi pH and cystic fibrosis.
AB  - Cystic fibrosis (CF) is associated with a defect in a cAMP-activated chloride
      channel in secretory epithelia, which leads to decreased fluid secretion. In
      addition, many mucus glycoproteins show decreased sialylation but increased
      sulphation. We have recently shown that the pH of intracellular organelles is
      elevated in CF cells, due to defective chloride conductance in the vesicle
      membranes. We postulate that this may affect the activity of sialyl-, fucosyl-
      and sulphotransferases, and thus explain the abnormal glycosylation. Defects in
      sialylation of glycolipids might also generate receptors for Pseudomonas, which
      infects the respiratory tract of CF patients.

PMID- 14731525
TI  - GTP-binding proteins in intracellular transport.
AB  - One of the most exciting recent discoveries in the area of intracellular protein
      transport is the finding that many organelles involved in exocytic and endocytic
      membrane traffic have one or more Ras-like GTP-binding proteins on their
      cytoplasmic face that are specific for each membranous compartment. These
      proteins are attractive candidates for regulators of transport vesicle formation
      and the accurate delivery of transport vesicles to their correct targets.

PMID- 14731526
TI  - The plasma membrane calcium pump: a multiregulated transporter.
AB  - Activation of many cells, especially nonexcitable cells, results in a Ca(2+)
      transient that is influenced in part by the kinetics of active extrusion of
      Ca(2+) across the plasma membrane. The molecular cloning of the plasma membrane
      Ca(2+)-pump has helped to clarify the relationship between its structure and
      function. The Ca(2+)-pump is controlled by multiple regulators, including
      calmodulin, phospholipids and various kinases. Longer term control is achieved
      through regulation of its gene expression, and the presence of a number of Ca(2+)
      pump isoforms that differ in their regulatory domains provides potential
      functional diversity. In this review, we focus on the mechanisms that regulate
      the function of the Ca(2+)-pump, and their physiological significance.

PMID- 14731527
TI  - Invariant chain--a regulator of antigen presentation.
AB  - MHC class II molecules present internalized antigens to the immune system. They
      have long been known to associate with a polypeptide called the invariant chain.
      Recent findings have revealed that this polypeptide performs two functions.
      First, it prevents class II molecules from binding antigenic peptides at the site
      of synthesis of class II molecules in the endoplasmic reticulum.Second, it
      targets class II molecules to their destination in the endocytic pathway, where
      they pick up antigenic peptides derived from endocytosed antigens. Short
      sequences in the cytoplasmic portion of the invariant chain serve as subcellular
      address labels. The functions of the invariant chain help to explain how the
      immune system divides its defence against foreign pathogens between cytotoxic T
      cells and antibodies.

PMID- 14731532
TI  - Twisting in a crowd.
AB  - Given our current understanding of nuclear structure, it is difficult to imagine
      how the nucleus performs its varied functions and controls the traffic of its
      many components. For example, how can densely packed chromatin be transcribed
      without the helical nature of the DNA resulting in entangled DNA and RNA and a
      stalled RNA polymerase? Here, Jacques Dubochet discusses a model of transcription
      in which DNA rotates around its axis, rather than RNA polymerase rotating around
      the DNA. Furthermore, he suggests that a view of chromatin as 'liquid' may help
      in understanding a wide range of nuclear functions.

PMID- 14731533
TI  - Signalling through SH2 and SH3 domains.
AB  - In 1986, Pawson's group recognized a region of homology between two oncogenic
      tyrosine kinases that lay outside the catalytic domain. They termed this the Src
      homology 2, or SH2, domain. In the ensuing years, SH2 domains have been found in
      an impressive variety of proteins, as has a second region of homology, inevitably
      termed SH3. These domains appear to mediate controlled protein-protein
      interactions. Many proteins that contain SH2 and SH3 domains are involved in
      signal transduction, suggesting a new paradigm for regulation of intracellular
      signalling pathways.

PMID- 14731534
TI  - Receptors for the TGF-beta superfamily: multiple polypeptides and
      serine/threonine kinases.
AB  - Members of the transforming growth factor beta (TGF-beta) superfamily of peptide
      growth factors have profound effects on the growth and differentiation of many
      cell types. Insights into the poorly understood mechanisms of action of these
      ligands have come from the recent molecular cloning of two types of high-affinity
      receptors - type II and type III - for TGF-beta superfamily members. The cell
      surface expression of the type III receptor, a membrane-bound proteoglycan,
      appears to modulate the binding of ligand to the type II receptor, which is a
      transmembrane serine/threonine kinase. These results provide evidence for
      interactions between different receptor types, and suggest that serine/threonine
      phosphorylation is an important element in TGF-beta-induced signalling.

PMID- 14731535
TI  - Participation of the bacterial membrane in DNA replication and chromosome
      partition.
AB  - The concept that the bacterial membrane plays an active role in the regulation of
      DNA replication and in segregation, or 'partition', of the bacterial chromosome
      at cell division was proposed in 1963. Membrane participation offered a
      relatively simple way to coordinate replication and partition. Some of the
      details of this model have been confirmed, while others have been changed. In
      fact, it appears that the membrane may play several distinct roles in these
      processes, and recent experiments have begun to identify the complexity of
      membrane involvement.

PMID- 14731536
TI  - Good ideas waiting to fuse.

PMID- 14731540
TI  - A turnstile for initiation of DNA replication.
AB  - The progress of a cell through its growth cycle is a multifaceted process; so far
      we have seen only a glimpse of the complex interplay between the macromolecules
      performing and regulating the different steps involved. In most organisms,
      control mechanisms ensure that all chromosomal DNA sequences are replicated once,
      and only once, between two cell divisions. This enables each division to produce
      two daughter cells with a genetic content identical to that of their mother.
      Although the biochemical synthetic processes involved in replicating DNA have
      been described in detail, our knowledge of the regulatory mechanisms of DNA
      replication remains scant. In recent experiments with Escherichia coli, new light
      has been shed on these elusive control mechanisms, and evidence has emerged that
      may signal an end to our ignorance about this important biological problem.

PMID- 14731541
TI  - Recombination and RNA processing: a common strand?
AB  - Genetic recombination is a basic cellular process required for altering genome
      structure. The RecA protein of Escherichia coli has a central role in homologous
      recombination, and a eukaryotic protein with similar properties has been
      discovered in the yeast Saccharomyces cerevisiae. Unexpectedly, this RecA-like
      protein has additional biochemical activities, and its function may not be
      restricted to recombination.

PMID- 14731542
TI  - Cyclin-dependent kinases: a new cell cycle motif?
AB  - Increasing evidence suggests that the eukaryotic cell cycle is controlled at
      several checkpoints by different members of a novel class of protein kinase, the
      cyclin-dependent kinases. To phosphorylate their substrates, these enzymes bind
      to proteins of the cyclin family--proteins that are synthesized and degraded at
      specific points in each cell cycle. The most well known of these kinases is the
      34 kDa product of the cdc2 gene in fission yeast, p34cdc2; however, several
      putative cyclin-dependent kinases have now been cloned or identified. Some of
      these closely resemble p34cdc2. Here we review these new proteins, their
      potential roles in the cell cycle and the cyclins with which they may interact.

PMID- 14731543
TI  - Motor proteins in cell division.
AB  - The movements of eukaryotic cell division depend upon the conversion of chemical
      energy into mechanical work, which in turn involves the actions of motor
      proteins, molecular transducers that generate force and motion relative
      cytoskeletal elements. In animal cells, microtubule-based motor proteins of the
      mitotic apparatus are involved in segregating chromosomes and perhaps in
      organizing the mitotic apparatus itself, while microfilament-based motors in the
      contractile ring generate the forces that separate daughter cells during
      cytokinesis. This review outlines recent advances in our understanding of the
      roles of molecular motors in mitosis and cytokinesis.

PMID- 14731544
TI  - Proteins controlling the nuclear uptake of NF-kappa B, Rel and dorsal.
AB  - The two DNA-binding subunits of the transcription factor NF-kappa B, the products
      of the rel oncogene family and the product of the developmental control gene
      dorsal of Drosophila are homologous within a 300 amino acid region. This sequence
      represents a novel DNA-binding and dimerization domain. The access of the NF
      kappa B/Rel/dorsal (NRD) transcription factor family to the cell nucleus is
      regulated. There is now evidence that functionally and structurally related
      accessory proteins of NF-kappa B, Rel and dorsal control the nuclear entry as
      well as DNA-binding activity of the transcription factors. This review summarizes
      current knowledge about the nuclear-uptake regulatory proteins (NURPs) I kappa B
      alpha, I kappa B-beta/pp40 and cactus.

PMID- 14731549
TI  - A role for oxygen radicals as second messengers.
AB  - All cells seem to produce oxygen radicals. Recent results suggest that small
      nontoxic amounts of these radicals are released by various cell types in response
      to stimulation with tumour necrosis factor (TNF), interleukin 1 (IL-1) and
      phorbol esters, all of which activate a cytoplasmic form of the transcription
      factor NF-kappa B by releasing an inhibitory protein subunit. Activation is
      inhibited by agents that remove oxygen radicals, and mimicked by exposure to mild
      oxidant stress. This article proposes that oxygen radicals act as second
      messengers for a variety of agents, including the immunomodulatory cytokines TNF
      and IL-1, in at least one type of regulatory pathway activating NF-kappa B.

PMID- 14731565
TI  - Unlocking vaults: organelles in search of a function.

PMID- 14731566
TI  - Novel myosins.
AB  - The traditional view of myosin, drawn from studies of myosins from striated
      muscles, is that of an elongated two-headed molecule that assembles into
      filaments. However, biochemical, molecular genetic and genetic studies have
      uncovered a host of ubiquitous single-headed nonfilamentous myosins known
      collectively as myosins I. All of the myosins I possess the myosin head domain,
      the motor portion of muscle myosins they have tail the filament-forming tail
      domain of muscle myosins they have tail domains that interact variously with
      membranes, actin and calmodulin. These alternative molecular interactions confer
      novel motile properties on myosins I, such as the ability to move membranes
      relative to actin and to move actin relative to actin without having to assemble
      into filaments. The numerous actin-based movements retained by cells lacking
      myosin II, the two-headed filamentous form of nonmuscle myosin, may be supported
      by myosins I.

PMID- 14731568
TI  - Developmental regulation of chromatin structure and function.

PMID- 14731567
TI  - Dynamin: a novel microtubule-associated GTPase.

PMID- 14731569
TI  - Probing replication origins with a fork.

PMID- 14731570
TI  - Artifacts in calcium measurement: recognition and remedies.

PMID- 14731576
TI  - Axillary surgery: is it necessary?

PMID- 14731577
TI  - Long-term follow-up of the first breast conservation trial: Guy' wide excision
      study.
AB  - Breast conservation therapy is now accepted as a proven approach for selected
      patients with operable breast cancer. Nevertheless, it is important to appreciate
      that the first randomized trials, which were carried out at Guy's Hospital,
      indicated the need for good local control and the increased mortality from breast
      cancer which occurred when treatment was sub-optimal. In the first trial 374
      women aged > or = 50, with T1, T2, N0 and N1 tumours were randomized to either
      Halsted mastectomy and postoperative radiotherapy or wide excision and
      postoperative irradiation. Both groups were given 25-27 Gy to the gland fields
      and the wide excision group received additionally 35-38 Gy to the breast. Hence
      the wide excision group had no axillary surgery and subsequent axillary
      irradiation using what is now regarded as a low dose of radiotherapy. After 25
      years, local relapse has occurred in 26% of the mastectomy group and 50% of the
      wide excision group (chi(2)= 21.6, P < 0.001). The breast cancer mortality rate
      at 25 years was 56% in the mastectomy group and 63% in those treated by wide
      excision (chi(2)= 5.33, P= 0.02). The first analysis of this trial indicated that
      increased risk of axillary relapse was restricted to N1 cases and so a second
      trial was conducted with entry only for those with clinically negative axillae
      (N0 series). Of 255 cases entered, 133 were randomized to mastectomy and 122 to
      wide excision. The same radiotherapy schedule was used as in the original Series.
      After 25 years local relapse occurred in 18% of the mastectomy cases and 54% of
      the wide excision group (chi(2)= 30.6, P < 0.001). There were significantly more
      distant relapse in the latter group (chi(2)= 6.32, P= 0.01), and a significant
      increase in breast cancer deaths (57% versus 44%, chi(2)= 4.27, P= 0.04). These
      two trials, conducted before the widespread introduction of systemic adjuvant
      therapy, both indicate the long-term effects of inadequate primary treatment.
      Inadvertent failure to treat the axilla effectively led not only to significantly
      increased axillary relapse rates but also to more deaths from metastatic disease.

PMID- 14731578
TI  - Open comparative trial of formestane versus megestrol acetate in postmenopausal
      patients with advanced breast cancer previously treated with tamoxifen.
AB  - The aim of the trial was to compare efficacy and safety of the aromatase
      inhibitor formestane (250 mg i.m. given every 2 weeks) with the progestin
      megestrol acetate (160 mg administered orally once daily), as second-line therapy
      in postmenopausal patients with advanced breast cancer previously treated with
      tamoxifen. A total of 547 patients were enrolled. Analyses revealed no
      statistically significant or clinically relevant difference between treatments
      with respect to time endpoints. In the intent-to-treat analysis, the median
      values for time to failure and overall survival for formestane were 169 and 561
      days, respectively. The corresponding values for megestrol acetate were 169 days
      and 597 days, respectively. Overall response rates were comparable for formestane
      and megestrol acetate (16.3% vs 20.3%). Formestane was better tolerated than
      megestrol acetate. In the megestrol acetate group, cardiovascular events, weight
      increase, and vaginal haemorrhage were significantly more frequent than in the
      formestane group. Thus, formestane is a suitable alternative to progestins in
      patients previously treated with tamoxifen.

PMID- 14731579
TI  - Clinical course and treatment results of breast cancer patients with ten or more
      positive axillary nodes.
AB  - Two-hundred and fifty-nine women with operable breast cancer, having more than 10
      involved nodes without a distant metastasis, were treated with radical, modified
      radical or partial mastectomy with complete axillary dissection. Survival at 5
      years was 63% and at 7 years 54%. Fifty-six per cent and 52% were disease free 5
      and 7 years after initial therapy. Postmenopausal women had an overall survival
      rate of 64% and disease free survival rate of 61% while premenopausal women had
      an overall survival of 58% and disease free survival of 52%. Survival and disease
      free survival rate for those with 10-20 positive nodes were 65% and 69%
      respectively, while for those with more than 20 positive nodes the rates were 49%
      and 52% respectively; a statistically better survival in the 2nd group. Although
      the observational time of patients having adjuvant CEF is short, a better
      survival rate and disease free survival rate is possible in women treated with
      CEF.

PMID- 14731580
TI  - Androgen receptor CAG repeat lengths in ductal carcinoma in situ of breast,
      longest in apocrine variety.
AB  - CAG repeat number in the androgen receptor (AR) has been associated with
      decreased prostate cancer risk, and AR expression has been found in female breast
      cancer, often associated with apocrine differentiation. Because trinucleotide
      expansion can alter gene expression and protein function, we hypothesized that it
      might occur in breast neoplasms. We used a repeat expansion detection technique
      to determine CAG repeat lengths in DNA from breast biopsies. Three lesion types
      were microdissected: fibroadenoma (48 cases), ductal carcinoma in situ (DCIS, 24
      cases), and invasive mammary carcinoma (18 cases). The maximum number of CAG
      repeats in either allele of each patient in these three groups was compared.
      Microsatellite repeat lengths in DCIS were longer than in fibroadenomas or
      invasive carcinomas (P= 0.017 comparing DCIS vs invasive carcinomas). Two cases
      of apocrine DCIS had very long repeat lengths, both exhibiting microsatellite
      lengths at the longest range of normal (32 and 33). Inherited differences in AR
      CAG length might influence the transition from DCIS to invasive breast cancer,
      perhaps by modulating function of AR in breast tissue. AR microsatellite
      polymorphisms could influence cellular differentiation in DCIS lesions, promoting
      formation of the apocrine subtype in the presence of longer CAG repeats.

PMID- 14731581
TI  - Assessment of endothelial cell proliferation in primary breast carcinoma and its
      association with axillary lymph node status.
AB  - The correlation between angiogenesis as assessed by endothelial cell
      proliferation in blood/lymphatic vessels in primary breast carcinomas, and
      axillary lymph-node metastasis was studied using a case-control design. Primary
      breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients
      (case), were compared with neoplasms from 45 node-negative patients (control).
      Vascularity, as assessed by vessel density, and endothelial cell proliferation
      were measured in a single tissue section using a double immunohistochemical
      staining technique using MIBI (Ki-67) and FVIII antibodies. No association
      between vascularity and node status was found (P > 0.70). Node positive breast
      carcinomas had, on average, significantly smaller proliferating vessels (140+/-7
      microm in perimeter) in the primary lesion when compared with node negative
      tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of
      relatively small vessels (less than 180 microm in perimeter) with proliferating
      endothelium was higher in node positive carcinomas than lymph-node negative
      neoplasms (P < 0.03). This association between node status and the size and
      frequency of blood/lymphatic vessels with proliferating endothelium in primary
      carcinoma may have important implications in metastasis.

PMID- 14731582
TI  - Effect of evening primrose oil on clinically diagnosed fibroadenomas.
AB  - The effects of oil of evening primrose oil on fibroadenomas was assessed over a 6
      month period. Eleven out of 21 (52%) of fibroadenomas receiving evening primrose
      oil and 8 out of 19 (42%) controls reduced in size. This study demonstrates that
      evening primrose oil does not significantly effect the natural history of breast
      fibroadenomas.

PMID- 14731583
TI  - Early stage breast cancer: costs and quality of life one year after treatment by
      mastectomy or conservative surgery and radiation therapy.
AB  - This paper reports a descriptive study of the costs and quality of life (QoL)
      outcome of treatments for early stage breast cancer in a cohort of Australian
      women, one year after initial surgical treatment. Mastectomy without breast
      reconstruction is compared to breast conserving surgery and radiotherapy (breast
      conservation). Of the 397 women eligible for the study, costing data were
      collected for 81% and quality of life data for 73%. The cost differences between
      treatment groups were mainly accounted for by adjuvant therapies, the more
      expensive being radiotherapy. When compared to women treated by mastectomy, those
      treated by breast conservation reported better body image but worse physical
      function. The negative impact of breast cancer and its treatment was greater for
      younger women, across a number of dimensions of quality of life (regardless of
      treatment type). While this study shows that breast conservation is more
      expensive than mastectomy, the QoL results reinforce the importance of patient
      participation in treatment decisions.

PMID- 14731584
TI  - Physiotherapy treatment of late symptoms following surgical treatment of breast
      cancer.
AB  - Women who have been subjected to surgical treatment for breast cancer may develop
      late sequelae in the area of operation on the chest wall and/or in the
      ipsilateral arm or shoulder after the immediate surgical discomfort has passed.
      As many patients seek treatment of their own accord by physiotherapists, we
      considered it relevant to evaluate the effect of two different physiotherapy
      regimes. We also wished to determine whether there was a possible relationship
      between occurrence of late sequelae and physical findings, carried out by means
      of a simple clinical examination based on physiotherapeutic methods of
      examination. Fifty-nine patients, 1-4 years postoperatively, were randomized to
      two different physiotherapy regimens. Patients were examined by a physician
      before and after the treatment, and they answered a questionnaire four times in
      all within the course of the investigation. The questionnaire covered six main
      late sequelae, as well as the degree of discomfort. Our investigation shows that
      many women experience late symptoms after surgical treatment of breast cancer,
      and that is possible in these patients, to demonstrate a reduction in strength in
      the ipsilateral extremity, reduced movement and increased muscle tone.
      Physiotherapy can improve the strength, movement and muscle tone in the operated
      extremity and also reduce the presence and severity of the late symptoms.

PMID- 14731585
TI  - A clinicopthologic study of a rare clinical entity mimicking breast carcinoma:
      idiopathic granulomatous mastitis.
AB  - Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory lesion of
      the breast clinically simulating carcinoma. The purpose of this report is to
      review the clinicopathological features of this clinical entity in a series of 18
      cases diagnosed in our institute. The notes of patients and the slides of the
      biopsy specimens of 18 cases with IGM were reviewed. Special stains for organisms
      and immunohistochemistry for T and B markers using the primary antibody was done.
      The diagnosis of IGM was made according to the criteria of Kessler and Wolloch.
      All but two patients were of reproductive age and all were parous. The main
      clinical finding was a unilateral, firm, discrete mass. All patients underwent
      excisional biopsy and recurrence was seen in three patients. In two of these
      patients who had recurrences, the prolactin level was high and reexcision
      combined with antiprolactinemic therapy was performed. The third patient was
      treated by reexcision and oral prednisone. There was granulomatous inflammation,
      centered mainly on breast lobules in all patients. T cell domination was
      observed. Exclusion of the other causes of a granulomatous lesion is necessary to
      make the diagnosis of IGM. The treatment of choice is unclear. Because of the
      clinical concern of malignancy, fine-needle aspiration cytology or core biopsy
      can be useful in some cases. To differentiate it from other granulomatous
      lesions, incisional biopsy or surgical excision of the lesion is necessary. In
      patients with delayed wound healing or recurrence after excisional biopsy, or
      those patients who have had an incisional biopsy only, if prolactin level is
      normal, reexcision and oral prednisone usage may be curative. In patients with a
      high prolactin level who have recurrence, medical treatment to control prolactin
      level may be useful in the management of these women.

PMID- 14731586
TI  - A rare case of breast cancer presenting as tetanus.

PMID- 14731587
TI  - Breast tuberculosis in a man.

PMID- 14731588
TI  - RNA helicases: modulators of RNA structure.
AB  - RNA molecules play an essential role in many cellular processes, often as
      components of ribonucleoprotein complexes. Like proteins, RNA molecules adopt
      sequence-specific secondary and tertiary structures that are essential for
      function; alteration of these structures therefore provides a means of regulating
      RNA function. The discovery of DEAD box proteins, a large family of proteins that
      share several highly conserved motifs and have known or putative ATP-dependent
      RNA helicase activity, has provoked growing interest in the concept that
      regulation of RNA function may occur through local unwinding of complex RNA
      structures.

PMID- 14731589
TI  - Endocytosis without clathrin.
AB  - Internalization of membrane, fluid and receptor-bound ligands into cells occurs
      by at least two endocytic mechanisms. One is dependent on clathrin and
      responsible for concentrative uptake of growth factors and other ligands, whereas
      the other operates without clathrin. Clathrin-independent endocytosis, which
      might involve more than one mechanism, can contribute significantly to the total
      uptake of membrane and fluid in a cell. The properties and possible roles of
      clathrin-independent endocytosis are discussed in this article.

PMID- 14731590
TI  - Nucleocytoplasmic mRNA transport: a plea for methodological dualism.

PMID- 14731591
TI  - Import of RNA into mitochondria.
AB  - RNAs that function in mitochondria, in contrast to the majority of mitochondrial
      proteins, are generally encoded by the mitochondrial genome. However, evidence
      has been presented for transport of nucleus-encoded tRNAs into mitochondria in
      diverse organisms. While mitochondrial protein import has been characterized in
      great detail, virtually nothing is known about the pathway of RNA import into
      mitochondria. Only very recently have in vivo systems for RNA import been
      established, and these are now providing some insight into this intriguing
      process.

PMID- 14731592
TI  - Protein phosphatase 2A--a 'menage a trois'.
AB  - Protein phosphorylation is probably the major regulatory mechanism employed by
      eukaryotic cells. Much work has been devoted to the role of protein kinases and
      their modulation by hormones, growth factors and neurotransmitters. It is now
      appreciated that protein phosphatases are also key players in actively regulating
      many cellular processes. In this article we discuss recent advances in our
      understanding of the function of protein phosphatase 2A, one of the major
      serine/threonine-specific protein phosphatases.

PMID- 14731593
TI  - Targeting of membrane proteins to endosomes and lysosomes.
AB  - The pathways involved in targeting membrane proteins to lysosomes are
      extraordinarily complex. Newly synthesized proteins in the ER are transported to
      the Golgi complex, and upon arrival at the trans Golgi network (TGN) are targeted
      either directly to endosomes, or first to the cell surface from where they can be
      rapidly internalized into the endocytic pathway for delivery to lysosomes. The
      routes to endosomes are specified by sorting motifs in the cytoplasmic tails of
      the proteins that are recognized at the TGN or plasma membrane. The molecular
      details of these processes are just emerging.

PMID- 14731594
TI  - Growth factors and the extracellular matrix.

PMID- 14731595
TI  - Protein tyrosine phosphatases: from structure to function.
AB  - In the past few years, a diverse family of receptor-like and nontransmembrane
      protein tyrosine phosphatases (PTPases) have been identified and characterized at
      the level of primary structure. Progress is now being made towards defining
      physiological processes in which the activity of PTPases is important. One thing
      seems clear: the PTPases cannot be regarded simply as antagonists of the protein
      tyrosine kinases (PTKs)--rather, they have the potential to act both positively
      and negatively in mediating cellular signalling responses.

PMID- 14731596
TI  - Universal cell cycle regulation?
AB  - The mechanisms that couple the control of initiation of chromosome replication
      and cell division to the mass increase of a growing cell are not understood.
      Here, models are considered in which replication and division are controlled
      through signals generated by completion of different morphological steps during
      cell cycle progression.

PMID- 14731597
TI  - Nitric oxide and the post-transcriptional control of cellular iron traffic.
AB  - Nitric oxide (NO) is a small, labile and highly reactive molecule generated in
      various cells by NO synthases. Several important biological functions are
      controlled by this messenger, and recent data suggest a novel direct role for NO
      in post-transcriptional gene regulation mediated by iron regulatory protein
      (IRP). IRP is a cytoplasmic protein that coordinates cellular iron traffic by
      binding to iron-responsive elements in mRNAs encoding proteins involved in iron
      uptake, storage and utilization. NO activates the RNA-binding activity of this
      protein and in this regard mimics the consequences of iron starvation. Cell
      biological and biochemical data on the functions of NO and IRP suggest a
      mechanistic basis for these findings and raise the question of their biological
      implications.

PMID- 14731598
TI  - Perichromatin fibrils are in situ forms of nascent transcripts.
AB  - Ultrastructural investigation of the cell nucleus has so far been the only high
      resolution approach for in situ analysis of its structural components and their
      roles in nuclear functions. Such studies have shown that perichromatin fibrils
      are the in situ form of hnRNA transcripts. Current evidence strongly supports the
      idea that they are also sites of pre-mRNA processing steps such as splicing and
      polyadenylation.

PMID- 14731599
TI  - Targeting of mRNAs to domains of the endoplasmic reticulum.
AB  - The targeting of proteins to specific regions of the cell by signal elements
      within the polypeptide sequence has received much attention, but proteins can
      also be directed to their appropriate cellular locations by localization of their
      mRNAs. This mechanism is seen clearly in polar cells like germ and embryonic
      cells, neurons and epithelia. Recent evidence indicates that mRNAs may also be
      localized to morphologically and functionally distinct endoplasmic reticulum
      membranes, thereby facilitating sorting of the proteins they encode to subdomains
      of the reticulum or to polarized plasma membranes.

PMID- 14731600
TI  - Cold fission: splitting the pombe cell at room temperature.
AB  - The mechanisms responsible for cytokinesis and its coordination with other events
      of the cell cycle are poorly understood. Genetic studies of cytokinesis in
      fission yeast are one useful approach to this problem. A number of conditional
      mutants of fission yeast that show defects in the formation of the septum of
      cytokinesis have been identified. Cloning of the genes affected in these mutants
      has begun to shed light upon the elements required to direct the construction of
      the division septum and also upon how the initiation of septum formation may be
      coordinated with mitosis.

PMID- 14731607
TI  - Apoptosis: suicide, execution or murder?
AB  - Apoptosis, a controlled form of cell death, appears to be regulated in several
      ways. Early studies indicated that de novo protein synthesis was required for
      apoptosis of thymocytes, but more recent studies have found that other cells can
      undergo apoptosis when protein synthesis is blocked or that inhibition of protein
      or RNA synthesis can induce apoptosis. Whether these findings reflect distinct
      forms of apoptosis or variations on a single pathway is not yet known. In this
      article the case for a single pathway to apoptosis, accessible at multiple
      points, is discussed.

PMID- 14731608
TI  - Coated-vesicle formation in vitro: conflicting results using different assays.
AB  - Cell-free systems provide essential tools for elucidating the molecular
      mechanisms underlying complex cellular processes such as vesicular transport. The
      biochemical utility of these model systems is strengthened by assays that allow
      rapid, quantitative detection of the events being studied. Two model systems have
      recently been developed to reconstitute coated-vesicle budding, and two different
      biochemical assays are used to detect this event. Striking differences in the
      biochemical requirements for 'coated-vesicle budding' are detected by these two
      assays, suggesting that two distinct events are being measured. These findings
      have wide implications for the use of cell-free assay systems in cell biology.

PMID- 14731609
TI  - hnRNP proteins: localization and transport between the nucleus and the cytoplasm.
AB  - The proteins of heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are
      among the most abundant proteins in the nucleus. They bind nascent pre-mRNAs and
      remain associated with them through their nuclear processing into mRNA. Recent
      findings indicate roles for hnRNP proteins in the biogenesis of mRNA and reveal a
      surprising intracellular localization pathway for these proteins. Several of the
      hnRNP proteins shuttle continuously between the nucleus and the cytoplasm, and
      the reaccumulation of the exported hnRNP proteins in the nucleus occurs by a
      novel process that is dependent on transcription by RNA polymerase II. These
      findings suggest possible novel functions for hnRNP proteins in the cytoplasm and
      in the nucleocytoplasmic transport of mRNA.

PMID- 14731610
TI  - Flagellar regeneration in Chlamydomonas: a model system for studying organelle
      assembly.
AB  - How do the many different components of an organelle assemble into a functional
      structure at an appropriate place and time? Flagellar regeneration by the
      biflagellate green alga Chlamydomonas is one experimental system in which
      genetics, biochemistry and ultrastructural analysis are being combined to
      investigate the assembly of a microtubule-containing organelle. Recent advances
      in the molecular biology of this 'green yeast' have made possible several new
      approaches to the problem of flagellar assembly; insights from these new
      approaches are the focus of this review.

PMID- 14731611
TI  - How transcription factors regulate origins of DNA replication in eukaryotic
      cells.
AB  - Eukaryotic chromosomes contain a few thousand origins of DNA replication, which
      are activated in a temporal and spatial order during S phase. One parameter that
      is strongly implicated in determining the order of replication is transcription.
      This review focuses on the role of transcription factors in activating origins of
      replication in eukaryotic cells. Studies of viral and mitochondrial replication
      origins have revealed several mechanisms by which transcription factors activate
      origins, but it remains to be seen whether any of these are used to regulate
      cellular chromosome replication.

PMID- 14731612
TI  - The ins and outs of the secretory pathway.

PMID- 14731619
TI  - A mitotic function for Src?
AB  - During mitosis, the activity of the c-Src protein tyrosine kinase increases. The
      tyrosine phosphorylation of a 68 kDa protein (Sam68) also increases at this time,
      and recent studies have shown that Src and Sam68 interact. Sam68 is highly
      related to p62, a RasGAP-associated protein, and has homology to RNA-binding
      proteins. The relationship between p62 and Sam68, and their roles in Src
      signalling, need to be clarified, but these findings suggest that Src may
      participate in regulating RNA processing during the cell cycle.

PMID- 14731620
TI  - Raf: the holy grail of Ras biology?
AB  - Ras proteins regulate cell growth and differentiation, and their mutation plays a
      major, direct role in causing human cancer. For years, their precise function has
      been a mystery. One of the pathways Ras controls has recently been identified. It
      consists of a cascade of kinases (Raf, MEK and MAP kinases) that transmits
      signals from the plasma membrane to the nucleus. The role of Ras is remarkably
      simple: it recruits Raf from the cytoplasm to the plasma membrane. Once in the
      membrane, Raf is activated and the kinase cascade is initiated. Is this the whole
      story?

PMID- 14731621
TI  - Is plasma membrane lipid composition defined in the exocytic or the endocytic
      pathway?
AB  - Compared with intracellular membranes, the plasma membrane is rich in cholesterol
      and sphingomyelin. How does this distinct composition arise? Here David Allan and
      Karl-Josef Kallen take a critical view of the belief that these lipids arrive at
      the plasma membrane via vesicular traffic from the Golgi complex and propose
      instead that they may be accreted in the endocytic recycling pathway.

PMID- 14731622
TI  - Beta-ARs in caveolae?

PMID- 14731624
TI  - Pores for thought: nuclear pore complex proteins.
AB  - Nuclear pore complexes (NPCs) are enormous macromolecular structures that mediate
      the active exchange of proteins and RNPs between the nucleus and cytoplasm.
      Recent work has resulted in a windfall of identified NPC polypeptides, many with
      unique sequences. Several of the proteins have been shown to be part of extended
      cytoplasmic and nucleoplasmic NPC filaments. Biochemical, structural and genetic
      studies on NPC proteins are just beginning to allow an understanding of how they
      associate into a functional organelle.

PMID- 14731625
TI  - The NP-C gene: a key to pathways of intracellular cholesterol transport.
AB  - Elucidation of the pathways for intracellular transport of cholesterol is an
      important yet elusive goal in cell biology. Analysis of the cellular defects in
      the human disease Niemann-Pick C (NP-C) is providing insights into this problem.
      Cholesterol derived from low-density lipoprotein accumulates in lysosomes of NP-C
      cells, apparently because intracellular movement of such cholesterol is blocked.
      Identification of the NP-C gene should provide crucial molecular clues to the
      mechanism of cholesterol transport within cells.

PMID- 14731626
TI  - Signal transduction pathways to apoptosis.
AB  - Recent work has demonstrated that a number of signalling events, including
      cytosolic Ca(2+) rises, cAMP accumulation, activation of protein kinase C,
      activation of protein tyrosine kinases, and production of ceramide, regulate
      apoptosis in diverse model systems. However, in some cells these signals promote
      apoptosis, whereas in others they block the response. This review discusses these
      observations and proposes explanations for how a given set of signal transduction
      systems might be involved in multiple cellular responses.

PMID- 14731630
TI  - Gamma-tubulin: the microtubule organizer?
AB  - Microtubules are composed predominantly of two related proteins: alpha- and beta
      tubulin. These proteins form the tubulin heterodimer, which is the basic building
      block of microtubules. Surprisingly, recent molecular genetic studies have
      revealed the existence of gamma-tubulin, a new member of the tubulin family. Like
      alpha- and beta-tubulin, gamma-tubulin is essential for microtubule function but,
      unlike alpha- and beta-tubulin, it is not a component of microtubules. Rather, it
      is located at microtubule-organizing centres and may function in the nucleation
      of microtubule assembly and establishment of microtubule polarity.

PMID- 14731631
TI  - Ca2+ measurements with fluorescent indicators in permeabilized cells.

PMID- 14731632
TI  - Telomeric position effect in yeast.
AB  - Telomeres are the physical ends of chromosomes. In yeast, when a gene is placed
      near a telomere, its transcription is repressed. Genes under the influence of
      this telomeric position effects switch between a repressed state and a
      transcriptionally active state, each of which is stable for many cell
      generations. Telomeric position effect may provide a model system for the study
      of heritable gene regulation in other, more complex organisms.

PMID- 14731633
TI  - Structure and molecular organization of the centromere-kinetochore complex.
AB  - For over a century, the terms centromere and kinetochore have been used
      interchangeably to describe a complex locus on eukaryotic chromosomes that
      attaches chromosomes to spindle fibres and facilitates chromosome movement in
      mitosis and meiosis. This region has become the focus of research aimed at
      defining the mechanism of chromosome segregation. A variety of new molecular
      probes and vastly improved optical-imaging technology have provided much new
      information on the structure of this locus and raised new hopes that an
      understanding of its function may soon be at hand.

PMID- 14731634
TI  - Cell polarity and morphogenesis in Saccharomyces cerevisiae.
AB  - Polarized cell growth and division are fundamental to cellular differentiation
      and tissue formation in eukaryotes. Analysis of cell polarity in the budding
      yeast Saccharomyces cerevisiae has allowed the identification of many regulatory,
      secretory and cytoskeletal components involved in these processes, as well as the
      elucidation of various steps in these events. Many of these components and
      processes may be similar in other eukaryotes.

PMID- 14731640
TI  - Intermediate filaments and lipoprotein cholesterol.
AB  - The ability of cells to utilize cholesterol derived from lipoprotein is important
      in plasma membrane biosynthesis, steroidogenesis and the regulation of sterol
      synthesis. While the endocytosis of lipoprotein-derived cholesterol has been well
      characterized, the subsequent events that mediate its post-lysosomal
      intracellular transport are not understood. Recent studies have suggested that
      vimentin-type intermediate filaments may have a role in cholesterol transport.
      The mechanism by which vimentin filaments affect this process is not known, but
      future studies promise to provide new insights into both the post-lysosomal
      transport of cholesterol and the intracellular functions of intermediate
      filaments.

PMID- 14731641
TI  - Calreticulin: from Ca2+ binding to control of gene expression.
AB  - Calreticulin is a highly conserved Ca(2+)-binding/storage protein of the
      endoplasmic reticulum (ER). Recently, it has been shown to play a role in the
      control of gene expression by interacting with the DNA-binding domain of various
      steroid receptors. How does this ER protein gain access to the nuclear steroid
      receptors? We propose that calreticulin undergoes unique intracellular
      trafficking that allows it to colocalize with and bind to steroid receptors.

PMID- 14731642
TI  - Quantal neurotransmitter release from early endosomes?

PMID- 14731643
TI  - The MCM2-3-5 proteins: are they replication licensing factors?
AB  - DNA replication occurs only once in each normal mitotic cell cycle. To explain
      this strict control, a 'licensing factor' was proposed to enter the nucleus
      periodically as the nuclear envelope disintegrates and reassembles at the end of
      mitosis. Inactivation of licensing factor immediately following initiation of DNA
      synthesis would prevent reinitiation until after the next mitosis. The MCM2-3-5
      proteins of Saccharomyces cerevisiae may be yeast's equivalent of licensing
      factor: they are present in the nucleus only between M and S phase, bind to
      chromatin and are important for the initiation of DNA replication.

PMID- 14731644
TI  - Cytoplasmic domains in eggs.
AB  - One way of organizing the body plan of a developing embryo is to establish
      domains in the egg with distinct compositions in defined spatial relationships to
      one another: when the egg divides up, these domains segregate preferentially to
      certain regions of the embryo and influence their development. In this review we
      discuss the nature, formation and reorganization of distinguishable domains in
      various eggs.

PMID- 14731645
TI  - The TGF-beta family and its composite receptors.
AB  - In their search for regulators of animal growth and development, biologists have
      often come upon members of the transforming growth factor beta (TGF-beta) family
      and have realized that these are among the most versatile carriers of growth and
      differentiation signals. New evidence suggests that these factors signal through
      receptors with remarkable structures. Each receptor is a complex of two distantly
      related transmembrane serine/threonine kinases that are both essential for
      signalling. TGF-beta and related factors have at their disposal a repertoire of
      such receptors, a feature that could account for their multifunctional nature.

PMID- 14731646
TI  - Clostridial neurotoxins: new tools for dissecting exocytosis.
AB  - Tetanus toxin and botulinal toxins are potent inhibitors of neuronal exocytosis.
      Within the past five years the protein sequences of all eight neurotoxins have
      been determined, their mode of action as metalloproteases has been established,
      and their intraneuronal targets have been identified. The toxins act by
      selectively proteolysing the synaptic vesicle protein synaptobrevin (VAMP) or the
      presynaptic membrane proteins syntaxin (HPC-1) and SNAP-25. These three proteins
      form the core of a complex that mediates fusion of carrier vesicles to target
      membranes. Tetanus and botulinal neurotoxins could serve in the future as tools
      to study membrane trafficking events, or even higher brain functions such as
      behaviour and learning.

PMID- 14731651
TI  - Towards the molecular physiology of cell movements.

PMID- 14731652
TI  - How do cells move along surfaces?
AB  - The movement of cells along surfaces is a complex phenomenon that consists of
      several interrelated processes, including cell-substratum adhesion, and extension
      and retraction of the cell edge, in which the actin cytoskeleton plays a crucial
      role. The past decade has seen increasingly detailed molecular-based
      investigations into cell motility, but it is still not known how molecular events
      are integrated to give cell movement. Molecular studies are now beginning to be
      linked to a more global concept of how whole cells move, and this combined
      approach promises to yield new insights into cell locomotion.

PMID- 14731653
TI  - Understanding the cortex of crawling cells: insights from Dictyostelium.
AB  - All animal cells are believed to use the same basic molecular mechanisms for
      locomotion when crawling on a surface. Study of a wide range of crawling cells
      has tended to confirm this belief but has also led to a diversity of hypotheses
      for locomotion and a bewildering list of candidate effector proteins. The
      emergence of a powerful model system, Dictyostelium discoideum, for the study of
      crawling of cells makes definitive tests of hypotheses for locomotion a reality.

PMID- 14731654
TI  - Microtubules, centrosomes and intermediate filaments in directed cell movement.
AB  - Cell movement involves the coordinated interaction of probably hundreds of
      components. The contractile apparatus based on actin, myosin and their associated
      proteins is involved in cell protrusion and force generation. Microtubules and
      intermediate filaments affect the distribution of membranous organelles and are
      also believed to determine cell shape and cell polarity. This review examines the
      way in which the distinct polarity of moving cells is influenced by microtubules,
      the microtubule-organizing centre and intermediate filaments. The observations
      summarized here suggest a broad spectrum of cell-type-specific differences in how
      these cytoskeletal components contribute to directional cell movement.

PMID- 14731655
TI  - Profilin as a potential mediator of membrane-cytoskeleton communication.
AB  - Profilin, the prototype actin-monomer-sequestering protein, has recently emerged
      as a multifunctional protein with several different activities. Genetic evidence
      in yeast and flies confirms that profilin is required for a normal actin
      cytoskeleton, while biochemical evidence suggests a role in regulating
      phosphoinositide signalling. New studies suggest that profilin may interact with
      other ligands, and even its role in regulating actin polymerization is now being
      re-evaluated.

PMID- 14731656
TI  - Regulation of leukocyte locomotion by Ca2+.
AB  - Neutrophils migrate towards sites of inflammation and infection by chemotaxis.
      Their motility is dependent on the actin cytoskeleton and on adhesion to
      extracellular substrates, but how these are regulated in response to stimuli is
      not clear. This review focuses on the potential role of Ca(2+) as a second
      messenger in neutrophil motility. Several effects of Ca(2+) and Ca(2+)-binding
      proteins on the stability and crosslinking of actin polymers have been
      demonstrated in vitro. Nevertheless, the complex mechanism by which Ca(2+)
      regulates actin in neutrophils is not fully understood. In addition,
      intracellular Ca(2+) regulates the intergin-mediated adhesion of neutrophils to
      extracellular matrix.

PMID- 14731657
TI  - Neural crest cell migration in the developing embryo.
AB  - In vertebrate embryos, neural crest cells migrate extensively to defined sites
      where they differentiate into a complex array of derivatives, ranging from
      neurons to pigment cells. Neural crest cells emerge uniformly from the neural
      tube but their subsequent migratory pattern is segmented along much of the body
      axis. What factors control this segmental migration? At trunk levels, it is
      imposed by the intrinsic segmentation of the neighbouring somitic mesoderm, while
      in the head, intrinsic information within the neural tube as well as extrinsic
      influences from the ectoderm are involved. A variety of cell-cell and cell
      extracellular matrix interactions are thought to influence initiation and
      movement of neural crest cells. This review summarizes recent progress from both
      experimental embryology and cell biology approaches in uncovering the mechanisms
      underlying neural crest cell migration.

PMID- 14731658
TI  - Dynein heavy chain isoforms and axonemal motility.
AB  - The translocation of dynein along microtubules is the basis for a wide variety of
      essential cellular movements. Dynein was first discovered in the ciliary axoneme,
      where it causes the directed sliding between outer doublet microtubules that
      underlies ciliary bending. The initiation and propagation of ciliary bends are
      produced by a precisely located array of different dyneins containing eight or
      more different dynein heavy chain isoforms. The detailed clarification of the
      structural and functional diversity of axonemal dynein heavy chains will not only
      provide the key to understanding how cilia function, but also give insights
      applicable to the study of non-axonemal microtubule motors.

PMID- 14731659
TI  - Chlamydomonas phototaxis.
AB  - Chlamydomonas has long been a favourite organism for genetic and biochemical
      studies of flagellar motility and assembly, photosynthesis, and organelle
      genomes. With the recent development of procedures for the efficient
      transformation of its nuclear genome, Chlamydomonas has become accessible to a
      wide range of molecular genetic approaches, including gene tagging by insertional
      mutagenesis and cloning by complementation. The availability of these powerful
      techniques is stimulating interest in Chlamydomonas as a model system for
      research in areas where it previously has not been widely exploited. One such
      area that holds particular promise is phototransduction and the behavioural
      response to light.

PMID- 14731660
TI  - The control of ciliary beat frequency.
AB  - Ciliary movement is powered by axonemal dynein. This article considers how a
      signal transduction cascade initiated at the cell membrane may activate outer
      dynein arms to change the velocity of microtubule sliding and the swimming speed
      of ciliated cells. For Paramecium, a critical event in the cascade is the cAMP
      dependent phosphorylation of a 29 kDa polypeptide that is associated with the
      outer dynein arm.

PMID- 14731661
TI  - Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis.
AB  - Caveolae, 50-100 nm invaginations that represent a subcompartment of the plasma
      membrane, have been known for many years, but their exact roles remain uncertain.
      The findings that the caveolae coat protein caveolin is a v-Src substrate and
      that G-protein-coupled receptors are present in caveolae have suggested a
      relationship between caveolae, caveolin and transmembrane signalling. The recent
      isolation of caveolin-rich membrane domains in which caveolin exists as a hetero
      oligomeric complex with integral membrane proteins and known cytoplasmic
      signalling molecules provides support for this hypothesis. Compartmentalization
      of certain signalling molecules within caveolae could allow efficient and rapid
      coupling of activated receptors to more than one effector system.

PMID- 14731662
TI  - Kinesin-like proteins in the flagella of Chlamydomonas.
AB  - The flagella of the biflagellate unicellular alga Chlamydomonas have long been
      known to contain the microtubule-dependent motor protein dynein, but recent
      findings indicate they also contain multiple members of the kinesin superfamily.
      Two of these kinesin-like proteins are restricted to a single central-pair
      microtubule, raising the question of how proteins are targeted to specific
      microtubules within the flagellum. The kinesin-like proteins on the central-pair
      microtubules may cause the central-pair apparatus to rotate or twist during
      flagellar beating. Other kinesins within the flagellum may participate in
      movements associated with the flagellar membrane.

PMID- 14731663
TI  - Virulence protein export systems in Salmonella and Shigella: a new family or lost
      relatives?
AB  - A number of Gram-negative bacterial pathogens secrete 'virulence determinants'
      directly into the extracellular medium, where they interact with host cells to
      promote disease. The study of the secretion machinery used by these organisms to
      transport specific virulence determinants out to the cell surface and beyond is
      of growing importance in the field of bacterial pathogenesis. Elements of the
      secretion machinery are shared by several pathogens. These homologous elements
      may lead to a better understanding of how the machinery works, but the unique
      elements will tell us more about what distinguishes one bacterial pathogen from
      another.

PMID- 14731664
TI  - Approaches to understanding auxin action.
AB  - The effects of auxin on plant growth and development have been studied for
      decades, but the molecular mechanisms of auxin action remain unknown. These
      mechanisms have primarily been investigated by characterization of auxin
      physiology mutants and analysis of auxin-binding proteins and auxin-regulated
      genes. These efforts are now converging, since some mutants have recently been
      shown to have altered expression of specific auxin-binding proteins and auxin
      regulated genes. The features of these proteins and genes are providing the first
      tantalizing clues to the organization of auxin signal transduction pathways.

PMID- 14731665
TI  - Control of SV40 DNA replication by protein phosphorylation: a model for cellular
      DNA replication?
AB  - SV40 DNA replication has been studied extensively as a model for eukaryotic DNA
      replication. The initiation of SV40 DNA replication depends on certain cellular
      enzymes and on a multifunctional viral phosphoprotein, T antigen, whose activity
      is controlled positively and negatively by its phosphorylation state. Several
      cellular protein kinases and phosphatases that act on T antigen have now been
      identified. The recent elucidation of the step in initiation that is sensitive to
      T antigen's phosphorylation state raises the question of whether initiation of
      cellular DNA replication may utilize a similar regulatory mechanism.

PMID- 14731666
TI  - The structural bases of integrin-ligand interactions.
AB  - Many extracellular matrix (ECM) proteins, particularly those in the vascular
      system, use their classical integrin-recognition motif Arg-Gly-Asp (RGD) to
      interact with integrins. The RGD motif is generally located in flexible peptide
      loops whose variable conformation enables the relatively few integrins with broad
      specificity, such as alpha(v)beta(3) and alpha(IIb)beta(3), to bind to a large
      variety of different ECM proteins. However, certain ECM constituents, such as
      collagens and laminins, interact with integrins in a conformation-dependent
      manner, in which both the linear structure and spatial arrangement of the
      polypeptides are important for the formation of active binding sites. These
      interactions provide high specificity for the communication of cells with
      distinct members of the ECM.

PMID- 14731667
TI  - Standing-wave excitation for fluorescence microscopy.

PMID- 14731675
TI  - Old cells never die, they just apoptose.

PMID- 14731676
TI  - Heat-shock proteins maintain the viability of ATP-deprived cells: what is the
      mechanism?
AB  - ATP depletion causes necrosis in mammalian cells. However, a previous heat shock
      can protect cells from the effects of energy deprivation, probably as a result of
      the synthesis and accumulation of heat-shock proteins (hsps). We propose that
      hsps protect ATP-depleted cells from rapid necrotic death by inhibiting the
      aggregation of cytoskeletal proteins that occurs when ATP synthesis is blocked.

PMID- 14731677
TI  - Salmonella entry into mammalian cells: different yet converging signal
      transduction pathways?
AB  - Salmonella bacteria have evolved means to subvert host cell signal transduction
      pathways to induce their uptake. Recently, progress has been made towards
      defining those pathways. Although it is clear that Salmonella evoke different
      signalling pathways in different cell lines, it is possible that these responses
      may be triggered by a common mechanism and that the diverse pathways may converge
      downstream in common effector molecules.

PMID- 14731678
TI  - The decision to enter mitosis.
AB  - The phosphotyrosine content of the cdc2 protein kinases, the catalytic component
      of maturation-promoting factor (MPF), is an important parameter of mitotic
      regulation in a variety of organisms. Recent studies have shed considerable light
      on how the cdc2-specific tyrosine kinase (wee1) and its competing phosphatase
      (cdc25) are regulated during the cell cycle. A goal for the future will be to
      obtain a comprehensive picture of how the wee1-cdc25 regulatory system
      collaborates with other steps in mitotic activation to ensure that cell division
      occurs at the appropriate time during the cell cycle.

PMID- 14731679
TI  - JAK protein tyrosine kinases: their role in cytokine signalling.
AB  - Protein tyrosine kinases (PTKs) are integral components of the cellular machinery
      that mediates the transduction and/or processing of many extra- and intracellular
      signals. Members of the JAK family of intracellular PTKs (JAK1, JAK2 and TYK2)
      are characterized by the possession of a PTK-related domain and five additional
      homology domains, in addition to a classical PTK domain. An important
      breakthrough in the understanding of JAK kinases function(s) has come from the
      recent observations that many cytokine receptors compensate for their lack of a
      PTK domain by utilizing members of the JAK family for signal transduction.

PMID- 14731680
TI  - LPA: a novel lipid mediator with diverse biological actions.
AB  - Lysophosphatidic acid (LPA), the smallest and structurally simplest phospholipid,
      is a platelet-derived serum factor that evokes a wide range of biological
      effects, including stimulation of fibroblast proliferation, platelet aggregation,
      cellular motility, tumour cell invasiveness and neurite retraction. This review
      summarizes recent insights into the mode of action of LPA. LPA appears to
      activate its own G-protein-coupled receptor(s) to initiate both classic and novel
      signal cascades. Of particular interest is LPA's ability to activate the Ras
      pathway and to stimulate protein tyrosine phosphorylation in concert with
      remodelling of the actin cytoskeleton.

PMID- 14731682
TI  - Protein kinase C: interactions and consequences.

PMID- 14731681
TI  - First thoughts on lipid second messengers.

PMID- 14731687
TI  - Receptor tyrosine kinase signalling: not so complex after all?
AB  - Receptor tyrosine kinases (RTKs) transmit intercellular signals that control many
      cellular events including proliferation, differentiation and cell survival.
      Ligand-bound RTKs regulate a complex network of intracellular signalling
      pathways. However, activation of just one of these pathways, which involves Ras
      and MAP kinase, is both necessary and sufficient to mediate the diverse
      developmental effects of several invertebrate RTKs. This article discusses these
      findings, which suggest that RTK-induced activation of MAP kinase in
      invertebrates acts as a simple developmental switch in multiple cell types, and
      considers the evidence that the Ras-MAP-kinase pathway also plays a similar role
      in vertebrates.

PMID- 14731688
TI  - Nucleolar proteins that bind NLSs: a role in nuclear import or ribosome
      biogenesis?
AB  - In a search for proteins that bind nuclear localization sequences (NLSs), a
      number of nucleolar proteins with diverse functions were found. It is thought
      that the assay fortuitously uncovered a novel domain that mediates the
      interaction between these nucleolar proteins and ribosomal proteins containing
      NLS-like sequences. The domain is highly acidic and contains a number of serines
      forming putative casein kinase II sites. Here, we propose a model in which the
      nucleolar proteins catalyse the assembly of ribosomal proteins with pre-rRNA.

PMID- 14731689
TI  - Are beta-ARs internalized via caveolae or coated pits?

PMID- 14731690
TI  - The Fas/APO-1 receptor and its deadly ligand.
AB  - The cell surface receptor Fas/APO-1 and its ligand have recently been identified
      as important mediators of apoptosis. Both molecules are crucial for the
      maintenance of a sound immune system, and when defective they give rise to severe
      autoimmune disorders. Understanding the mechanism and regulation of Fas/APO-1
      triggered cell death promises important insights for the pathogenesis of AIDS,
      cancer and autoimmune diseases.

PMID- 14731691
TI  - Protein tyrosine phosphatases in disease processes.
AB  - Given the importance of tyrosine phosphorylation of proteins in signalling
      pathways, it is perhaps not surprising that protein tyrosine phosphatases (PTPs)
      are involved in the pathogenesis of certain human diseases. A PTP produced by the
      Yersinia bacteria (which can cause bubonic plague, septicemia and enteric
      diseases) is thought to be used as a 'weapon' against host cell functions. In
      addition, dysfunction of cells' endogenous PTPs may contribute to defective
      immune function, to cancer and to diabetes.

PMID- 14731693
TI  - Completing the next phase of the cycle: Kyoto to Cambridge.

PMID- 14731692
TI  - Ca2+ release induced by cyclic ADP-ribose.
AB  - Cyclic ADP-ribose (cADPR) is the most potent Ca(2+)-mobilizing agent known. It
      has been found in many different cell types, where it is synthesized from its
      precursor NAD(+) by ADP-ribosyl cyclases. cADPR binds to Ca(2+) channels in the
      endoplasmic reticulum membrane to activate a Ca(2+)-release mechanism. This
      release is itself potentiated by elevated cytoplasmic Ca(2+) concentrations.
      Thus, cADPR may function as an endogenous regulator of Ca(2+)-induced Ca(2+)
      release, and there is excitement that it may also function as a Ca(2+)-mobilizing
      second messenger.

PMID- 14731694
TI  - 2-D protein gel electrophoresis: an old method with future potential.

PMID- 14731700
TI  - Quality assurance in breast screening in Europe.
AB  - An extensive pathology External Quality Assurance has been set up in Europe based
      on the experience of the UK programme. There are approximately 300 participating
      pathologists in France alone. With the end of the Third Action Plan (1996-2000)
      it is likely that the Europe Against Cancer programme will cease. However,
      screening will remain one of the four major public health activities funded by
      the European Commission and the screening network which has resided under the
      auspices of DGV (Industrial Relations and Social Affairs) is likely to be
      transferred to DGXXIV (Consumer Protection and Public Health). This would seem to
      be ideal the site for the activities necessary for high quality screening. It is
      anticipated that the drive for continued quality assurance, expansion of
      organised screening and the spread of skills from high quality screening
      programmes into symptomatic sector activity will continue for the foreseeable
      future.

PMID- 14731701
TI  - Radial scar.
AB  - Radial scars attract interest due to its mammographic appearance and pathology.
      It is still unclear whether it is a benign or premalignant condition. This
      article reviews the clinical feature, pathology and its relation to malignancy.

PMID- 14731702
TI  - Rationale for a national multi-centre study of magnetic resonance imaging
      screening in women at genetic risk of breast cancer.
AB  - In 1994, the UK National Health Service identified as a research priority that
      magnetic resonance imaging (MRI) should be assessed as a screening tool for
      young, pre-menopausal women who are at a high genetic risk of developing breast
      cancer. In 1997 a national multicentre study was established to compare MRI with
      X-ray mammography as a method for screening for breast cancer in this group of
      women. This paper reviews the relevant literature and describes the rationale
      that led to the setting up of this study.

PMID- 14731703
TI  - Protocol for a national multi-centre study of magnetic resonance imaging
      screening in women at genetic risk of breast cancer.
AB  - The protocol of the national multicentre study of Magnetic Resonance Imaging
      (MRI) as a method of screening for breast cancer in women at genetic risk is
      described. The sensitivity and specificity of contrast-enhanced MRI will be
      compared with two-view X-ray mammography in a comparative trial. Approximately
      500 women below the age of 50 at high genetic risk of breast cancer will be
      recruited per year for 3 years, with annual MRI and X-ray examination continuing
      for up to 5 years. A symptomatic cohort will be measured in the initial phase of
      the study to ensure consistent reporting between centres. The MRI examination
      will comprise an initial high-sensitivity screening measurement, followed by a
      high-specificity measurement in equivocal cases. Retrospective analysis will
      identify the most specific indicators of malignancy. Sensitivity and specificity,
      together with diagnostic performance, diagnostic impact and therapeutic impact
      will be assessed with reference to pathology, follow-up and changes in diagnostic
      certainty and therapeutic decisions. The psychological impact of screening in
      this high-risk group will be ascertained.

PMID- 14731704
TI  - Family history in breast cancer is not a prognostic factor?
AB  - The aim of this study is to determine if breast conservative treatment is
      justified for patients with a positive family history of breast cancer and to
      investigate whether they have a worse prognosis. We performed a prospective
      cohort study of breast cancer patients, treated with breast conservative
      treatment with radiotherapy at the Radiotherapy Department of the Medisch
      Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 < or =3 cm
      were treated. Family history (FH) was recorded according to first degree relative
      (FDR). Treatment consisted of lumpectomy with axillary dissection followed by
      radiotherapy to the whole breast with a boost to the primary area. Adjuvant
      systemic therapy was given to patients with positive nodes. A positive FH was
      noted in 243 (20.5%) patients, of whom 208 (17.6%) had one FDR, and 35 (3.0%) >
      or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all
      groups. In young patients, < or =40 years, a significant relation between local
      recurrence and FH was found. The distant metastasis rate was 15.5%, with the
      lowest rate (5.7%) among patients with > or =2 FDRs. Patients with a positive FH
      had significantly more contralateral tumours. The 5-year corrected survival was
      91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was
      observed and the survival 100% among patients with one and > or =2 FDR. Family
      history is not a contraindication for breast conservative treatment and is not
      associated with a worse prognosis. Family history is not a prognostic factor for
      local recurrence rate in patients older than 40 years.

PMID- 14731705
TI  - Intraoperative axillary lymph node assessment in breast cancer.
AB  - Bedside assessment of axillary lymph node metastases in breast cancer is
      notoriously inaccurate. The aim of this study was to assess the accuracy of the
      clinical assessment of the presence of axillary node metastases in patients with
      breast cancer, both at the bedside and intraoperatively. Intraoperative
      assessment was significantly more accurate than bedside assessment, having an
      accuracy of 86%, compared with 66% of bedside clinical assessment. As axillary
      lymph node involvement is an important prognostic factor in breast cancer, this
      technique which has a high specificity and far higher sensitivity than bedside
      clinical assessment and may have a valuable role to play in planning management.

PMID- 14731706
TI  - Early discharge with drain in situ following axillary lymphadenectomy for breast
      cancer.
AB  - One-hundred and two women had axillary lymphadenectomy for breast cancer and were
      randomised to early discharge with axillary drain in situ on the third
      postoperative day or standard duration 7 day hospital stay. The two groups did
      not differ with respect to seroma formation, wound infection or psychological
      profile as measured by the Hospital Anxiety and Depression Scale and Spielberger
      State Trait and Anxiety Inventory. Patient satisfaction levels were high in the
      early discharge group. The results confirm that early discharge after axillary
      lymphadenectomy is safe, practicable and satisfactory for patients. Such a policy
      offers considerable resource savings.

PMID- 14731707
TI  - Mastectomy follow-up by biennial mammograms: is it worthwhile?
AB  - The value of follow-up after mastectomy for breast cancer is controversial. One
      reason is to detect metachronous tumour in the contralateral breast, but the
      optimum method for achieving this is undecided. The long-term follow-up policy of
      our unit is annual clinical review combined with biennial mammography. We have
      assessed the benefit of this policy in the detection of tumours of the
      contralateral breast. The case notes of 216 patients undergoing mastectomy
      between 1978 and 1985, under the care of one consultant surgeon (DJTW) were
      reviewed. Follow-up was complete to December 1997, thus allowing a minimum follow
      up of 12 years. The development of a metachronous tumour was recorded as was its
      method of detection : either clinically, by the patient or the clinician, or by
      routine mammography. Two-hundred and five patients were available for follow-up
      of the contralateral breast. Seventeen (8.3%) developed metachronous tumours.
      Eight were detected by the patient, 4 by the clinician and 5 by routine follow-up
      mammography. Biennial mammography does not appear to be beneficial in breast
      cancer follow-up. More work is required to determine the benefits of more
      frequent mammography, with or without breast self-examination and clinical review
      within the hospital environment or within primary care.

PMID- 14731708
TI  - Tamoxifen increases apoptosis but does not influence markers of proliferation in
      an MCF-7 xenograft model of breast cancer.
AB  - Twenty-four nude mice bearing MCF-7 breast cancer cells grown as xenografts and
      treated with tamoxifen (2.5 mg slow-release pellet) were studied for up to 35
      days. Tumour size was measured in 2 dimensions at regular time-intervals and
      tumours were harvested on each of days 2, 4, 7, 14, 28 and 35 after the start of
      treatment. Control animals (8) received no treatment and the tumours were
      harvested after 0 or 35 days. Tumour sections were assessed for prevalence of
      apoptosis and mitosis and examined immunocytochemically for Ki(67)(MIB-1) and bcl
      2 expression. Tumours increased in size during tamoxifen-treatment, but at a
      significantly slower rate (max. 2.6-fold) than in the untreated control animals;
      thus tumours not actually regressing may, nevertheless, be responding
      significantly to tamoxifen. MIB-1 and bcl-2 immunostaining and mitosis failed to
      show any consistent change over the period of study. Apoptosis, however,
      increased progressively and significantly to day-28 in tamoxifen-treated tumours,
      reaching approximately a 5-fold increase over day-0 values, then decreasing again
      to nearly 3-fold by day-35 (P= 0.0002). The apoptosis: mitosis ratio in treated
      tumours also increased to approximately 10-fold on day-28 over day-0 values,
      decreasing to nearly 4-fold by day-35 (P= 0.037). Within the treated group,
      apoptosis was significantly inversely correlated with both mitosis (R = -0.38, P=
      0.03) and expression of bcl-2 (R = -0.48, P= 0.0056) and strongly positively
      correlated with both time on tamoxifen (R = +0.63, P= 0.0003) and the %
      inhibition of growth by tamoxifen (R = +0.58,P = 0.0012) in the 28 individual,
      treated tumours (estimated relative to the mean growth rate in the controls). The
      apoptosis: mitosis ratio was also inversely correlated with bcl-2 expression (R =
      -0.56, P= 0.0021) and positively correlated with both time on tamoxifen (R =
      +0.50, P= 0.0068) and % inhibition of growth (R = +0.56, P= 0.0019). In this
      hormone-sensitive tumour model for breast cancer, in which tamoxifen caused
      inhibition rather than regression, it was not possible to detect significant
      changes in the marker proteins Ki(67)and bcl-2, or in the prevalence of mitosis
      in relation to treatment; these factors may therefore not be accurate indices of
      response to tamoxifen in all situations. By contrast, however, tamoxifen induced
      a significant, early increase in the prevalence of apoptosis associated with
      inhibition of tumour growth and an inverse relationship in both mitosis and bcl-2
      expression, suggesting that apoptosis may be an accurate and sensitive early
      marker of even a moderate response to tamoxifen.

PMID- 14731709
TI  - Use of the site percutaneous breast biopsy device.
AB  - A new technique is described for image guided percutaneous diagnostic excision
      biopsy of non-palpable mammographically detected breast lesions. This method
      involves insertion of a localizing guide wire under stereotactic guidance
      followed by insertion of the 15 mm diameter biopsy device which is positioned
      within the breast immediately proximal to the target lesion. A cylindrical
      cannula is advanced over the lesion which is then separated from the surrounding
      breast tissue by deploying a garrote wire at the distal end of the cannula. The
      biopsy device is then removed with the target lesion contained within the
      cannula. The mammographic lesion is excised without removing any excess adjacent
      breast tissue, and in one piece, so allowing histological examination of the
      whole lesion. The experience of the first three cases is described with imaging
      and histological correlation.

PMID- 14731710
TI  - Pregnancy in a breast cancer patient treated with a LHRH analogue at ablative
      doses.
AB  - A 36-year-old female diagnosed of breast cancer was treated with surgery,
      chemotherapy, radiotherapy and goserelin. After 17 months of uninterrupted
      therapy with this LHRH analogue at hormone suppressive doses, a 16-week gestation
      foetus was detected and the treatment was withdrawn. Although the drug was
      administered throughout the first 4 months of pregnancy it resulted in the term
      delivery of a healthy infant, and no foetal adverse effects were detected. A
      review of the influence of hormonal treatment for breast cancer on fertility and
      birth defects has been performed.

PMID- 14731711
TI  - Nipple aspirate fluid in relation to breast cancer.

PMID- 14731712
TI  - Rapid preoperative assessment of axillary lymph node status using imprint
      cytology.

PMID- 14731715
TI  - Towards the cellular functions of tumour suppressors.
AB  - Many of the documented changes in cellular DNA that occur during tumour
      development involve activation of proto-oncogenes, but newer evidence has shown
      that oncogenesis can involve loss or inactivation of a different group of genes,
      called tumour suppressor genes (TSGs). Molecular analysis of TSGs is revealing
      that their protein products are involved in cell adhesion, signal transduction,
      transcription, translation and cell cycle control. Surprisingly, most of the TSG
      products had not been previously identified in studies of normal cells, so their
      analysis is contributing not only to our understanding of oncogenesis, but also
      to basic cell biology. The 'comment' articles in this issue discuss progress
      towards understanding the cellular functions of TSG products.

PMID- 14731716
TI  - Cell adhesion molecules as tumour suppressors.
AB  - Cell adhesion molecules, a diverse group of proteins expressed on the cell
      surface, have been implicated in numerous important cellular functions ranging
      from controlling morphogenesis to suppressing tumourigenesis. In this article, we
      discuss evidence supporting the idea that at least some proteins involved in cell
      adhesion may suppress tumourigenesis through influences on cell growth,
      differentiation and/or invasion. These studies suggest that some cell adhesion
      molecules may be encoded by tumour suppressor genes.

PMID- 14731717
TI  - Tumour suppressors and the regulation of GTP-binding protein activity.
AB  - GTP-binding proteins regulate a wide variety of intracellular signalling pathways
      in eukaryotic cells. The Ras GTP-binding proteins have received a great deal of
      attention since they were found to be modified by amino acid substitutions in a
      large number of cancers. It is now clear that Ras plays an essential role in
      regulating normal cell growth and differentiation, although how this is achieved
      biochemically is not known. The cellular concentration of Ras bound to GTP
      appears to be the limiting factor for signalling, and, not surprisingly, it is
      tightly controlled by both positive and negative regulators. There is now
      convincing evidence that the loss of one of these negative regulators of Ras,
      neurofibromin, can contribute to the development of malignancy; thus,
      neurofibromin behaves as a tumour suppressor gene product.

PMID- 14731718
TI  - The retinoblastoma protein as a transcriptional repressor.
AB  - The retinoblastoma protein (pRB) is one of the best-studied tumour suppressor
      gene products. Its loss during the genesis of many human tumours, its
      inactivation by several DNA tumour virus oncoproteins, and its ability to inhibit
      cell growth when introduced into dividing cells all suggest that pRB negatively
      regulates some aspect of normal cell growth. The discovery that pRB associates
      with transcription factors such as E2F has provided the first model for pRB
      function. In this review, we discuss how pRB may regulate cell growth by
      repressing transcription of genes essential for cell proliferation.

PMID- 14731719
TI  - In search of the functions of normal p53 protein.
AB  - p53 is of major importance in protecting cells from neoplasia. Most human tumours
      have an abnormal or inactivated p53 protein. Furthermore, when expression of
      normal p53 is reinstated in cancer cell lines, they undergo growth suppression
      leading to either cell differentiation or programmed cell death. But is p53
      involved in the regulation of normal cell growth and differentiation in vivo?
      Here, Varda Rotter and colleagues critically assess some recent conflicting data
      on this issue.

PMID- 14731729
TI  - A new ATP-binding fold in actin, hexokinase and Hsc70.
AB  - One of a cell biologist's favourite occupations is to discover the proteins that
      perform newly described functions in the cell. Very often lately, this has
      resulted in the identification of protein families whose related amino acid
      sequences reflect similar functions, but can proteins with totally unrelated
      sequences have similar structures and functions? In this review, Ken Holmes,
      Chris Sander and Alfonso Valencia describe the structural similarities between
      three well-known proteins that have no readily detectable primary sequence
      similarities but for which X-ray crystallography has revealed very similar
      structures. A comparison of their structures provides insights into their common
      mechanisms of action and into protein evolution, and has been used to detect
      related proteins in sequence data bases.

PMID- 14731730
TI  - Signal transduction during mating and meiosis in S. pombe.
AB  - When starved, the fission yeast Schizosaccharomyces pombe responds by producing
      mating factors or pheromones that signal to cells of the opposite sex to initiate
      mating. Like its distant relative Saccharomyces cerevisiae, cells of the two
      mating types of S. pombe each produce a distinct pheromone that binds to
      receptors on the opposite cell type to induce the morphological changes required
      for mating. While the pathways are basically very similar in the two yeasts,
      pheromone signalling in S. pombe differs in several important ways from that of
      the more familiar budding yeast. In this article, Olaf Nielsen describes the
      pheromones and their effects in S. pombe, and compares the signalling pathways of
      the two yeasts.

PMID- 14731732
TI  - The inner world of cell adhesion: integrin cytoplasmic domains.
AB  - Many of the interactions between cells and their environment are mediated by the
      integrin family of heterodimeric transmembrane receptors. The past decade has
      been a broad-based effort to decipher the rules by which integrins function.
      Integrins bind both intracellular and extracellular ligands and thus transfer
      signals across the membrane in both directions. The cytoplasmic domains of these
      receptors play a key role in this bidirectional flow of information and in the
      formation of direct physical linkages between protein structures on the inside
      and outside of the cell.

PMID- 14731733
TI  - Insulin signalling: the role of insulin receptor substrate 1.
AB  - The insulin receptor is a ligand-activated tyrosine kinase that phosphorylates
      its major substrate protein, insulin receptor substrate 1 (IRS1), at multiple
      sites. Tyrosine-phosphorylated IRS1 then serves as a docking/effector protein for
      at least four Src homology 2 (SH2)-domain proteins involved in signal
      transduction. This initial step in signalling distinguishes the insulin receptor
      from other receptor tyrosine kinases, which directly bind several SH2-domain
      proteins, and establishes IRS1 as a founding member of a group of proteins whose
      function is to link activated tyrosine kinases to SH2-domain proteins.

PMID- 14731734
TI  - Insulin stimulation of GLUT-4 translocation: a model for regulated recycling.
AB  - Insulin stimulates glucose transport in muscle and fat cells by causing the
      redistribution of a facilitative glucose transporter, GLUT-4, from an
      intracellular compartment to the cell surface. But what is this intracellular
      GLUT-4 compartment? It may be a specialized compartment, perhaps analogous to
      synaptic vesicles, or may simply be part of the endosomal system. Other
      constituents of this compartment might be regulators of GLUT-4 movement to the
      cell surface, and their identification should make it possible to find the link
      between the insulin signal transduction pathway and GLUT-4 translocation.

PMID- 14731735
TI  - Integral membrane proteins and dynamic organization of the nuclear envelope.
AB  - The nuclear envelope is a complex structure consisting of nuclear membranes,
      nuclear pore complexes and lamina. Several integral membrane proteins specific to
      the nuclear pore membrane and the inner nuclear membrane are known. Pore membrane
      proteins are probably important for organization and assembly of the nuclear pore
      complex, while proteins of the inner nuclear membrane are likely to play major
      roles in the structure and dynamics of the nuclear lamina and chromatin.
      Biochemical studies are now identifying potential binding partners for some of
      these integral membrane proteins, and analysis of nuclear envelope assembly at
      the end of mitosis is providing important insights into their functions.

PMID- 14731736
TI  - Travelling in style: the cell biology of pollen.
AB  - Pollen grains of flowering plants are highly specialized two- to three-cell
      gametophytes that deliver sperm to the ovule. This function is achieved as a
      result of a complex developmental programme, including the coordinated events of
      meiotic divisions, the production of a unique extracellular matrix, the
      establishment of cytoplasmic domains, and a determinative asymmetric cell
      division. After maturation, pollen must interact specifically with the receptive
      female tissues and germinate a highly polarized pollen tube that rapidly grows
      through the style to the ovule. Thus, pollen is an excellent model system for the
      study of meiotic events, cellular organization, cell-cell interactions and polar
      growth in plant biology.

PMID- 14731737
TI  - Autophagy and related mechanisms of lysosome-mediated protein degradation.
AB  - Lysosomes play a central role in the degradation of extracellular and
      intracellular macromolecules. These organelles contain hydrolytic enzymes capable
      of degrading proteins, proteoglycans, nucleic acids, and lipids. The mechanisms
      involved in the delivery of such intracellular compounds to the lysosome have
      been characterized in several recent studies. The sequestration of intracellular
      macromolecules for intralysosomal degradation can occur by crinophagy, hsc73
      mediated carrier transport, or autophagy. The major route of delivery of cellular
      proteins and RNA into lysosomes is by autophagy. Furthermore, autophagy is
      regulated by nutrients and hormones, thus allowing the cell to adjust its
      degradative state to environmental changes.

PMID- 14731741
TI  - Are caveolae involved in clathrin-independent endocytosis?
AB  - In addition to endocytosing molecules via clathrin-coated pits, cells also
      internalize membrane and fluid by a clathrin-independent endocytic mechanism. In
      this article we search for the equivalent of clathrin-coated pits in clathrin
      independent endocytosis, and discuss some pitfalls in the interpretation of
      electron micrographs. We also discuss how the early steps in clathrin-independent
      endocytosis might be analysed morphologically, and we argue that caveolae are not
      involved in clathrin-independent endocytosis.

PMID- 14731742
TI  - TGN38/41: a molecule on the move.
AB  - TGN38/41 is a heterodimeric integral membrane protein that cycles between the
      trans Golgi network and the cell surface. A tyrosine-containing tetrapeptide
      motif within its cytoplasmic tail is necessary and sufficient for determining its
      steady-state location in the TGN. Recent results have shown that TGN38/41 plays
      an essential role in the formation of exocytic vesicles at the TGN by serving as
      a receptor for complexes of a cytoplasmic protein known as p62, and one of four
      small GTP-binding proteins, including rab6. For budding to occur, this complex
      must bind to the cytoplasmic domain of TGN38/41. We propose here that TGN38/41
      may couple the segregation of secretory proteins to the budding of exocytic
      vesicles at the TGN.

PMID- 14731743
TI  - Focal adhesion kinase: an integrin-linked protein tyrosine kinase.
AB  - Recent evidence has shown that binding of integrins to components of the
      extracellular matrix serves to initiate cellular signals, resulting in changes in
      cytoskeletal architecture and activation of intracellular signalling pathways.
      Here we review the evidence that protein tyrosine kinases, including focal
      adhesion-associated kinases, play a central role in the generation of some of
      these molecular signals.

PMID- 14731744
TI  - The neurotrophins and their receptors.
AB  - The neurotrophins, which include nerve growth factor (NGF) and its relatives,
      were discovered and characterized for their distinctive ability to promote
      survival and differentiation of postmitotic neurons. Perhaps surprisingly, the
      neurotrophins have recently been found to utilize a family of receptor tyrosine
      kinases (the Trks) similar to those used by normally mitogenic growth factors. In
      fact, ectopic expression of the Trks in non-neuronal cells allows them to mediate
      conventional mitogenic responses to the neurotrophins. Despite similarities with
      other receptor tyrosine kinases, the Trks are rather unique in that they are
      almost exclusively expressed in the nervous system, and they also display a
      number of novel structural features. In addition to the Trks, the neurotrophins
      all bind to another cell surface receptor (known as p75 or the low-affinity NGF
      receptor), whose role remains quite controversial.

PMID- 14731745
TI  - Mx proteins: GTPases with antiviral activity.
AB  - Mx proteins are synthesized in interferon-treated vertebrate cells. They have
      attracted much attention because some of them can block the multiplication of
      influenza A virus and certain other negative-stranded RNA viruses. Recently, Mx
      proteins have been shown to be GTPases with significant homology to dynamins and
      yeast VPS1, enzymes involved in intracellular protein trafficking. Several
      biochemical properties of dynamin and VPS1 are similar to those of Mx, promoting
      new speculation about how Mx proteins might interfere with virus multiplication.

PMID- 14731746
TI  - Yeast endocytosis.
AB  - The presence of an endocytic pathway in cells from a wide range of species and
      the conservation of the proteins involved in this process throughout evolution
      suggest that endocytosis is of fundamental importance for the eukaryotic cell.
      However, some surprising recent results have shown that both Dictyostelium
      discoideum and Saccharomyces cerevisiae can live under laboratory conditions with
      substantially reduced levels of endocytosis. In this review, I concentrate on
      endocytosis in S. cerevisiae. Recent progress in the study of intermediates of
      the endocytic pathway and of mutants affecting the endocytic pathway make this
      organism an interesting model with which to study the mechanism and functions of
      endocytosis.

PMID- 14731747
TI  - Steroid-binding domains for regulating the functions of heterologous proteins in
      cis.

PMID- 14731754
TI  - Transcriptional regulation by the retinoblastoma protein.
AB  - The retinoblastoma protein (RB) plays a key role in the control of cell
      proliferation and mediates the terminal differentiation of certain cell types.
      Increasing evidence suggests that RB functions by contacting and modifying the
      behaviour of transcription factors. RB can form complexes with E2F and MyoD in
      vivo, and complexes with a number of other transcription factors have also been
      demonstrated in vitro. The interaction of regulatory transcription factors with
      RB may be explained by sequence similarity between RB and two general
      transcription factors: TBP and TFIIB. Here I review the evidence for a role of RB
      in the regulation of transcription and highlight some of the likely mechanisms of
      RB function.

PMID- 14731755
TI  - The immunofluorescent era of membrane traffic.
AB  - In recent years immunofluorescence microscopy has been increasingly used to study
      membrane traffic. In this article seven electron microscopists, all with
      considerable experience in using light microscopy, take a critical look at the
      immunofluorescence approach and argue that results obtained with this method are
      often overinterpreted.

PMID- 14731756
TI  - Basal-body-associated macromolecules: a continuing debate.
AB  - Controversy over the possibility that centrioles/basal bodies contain nucleic
      acids has overshadowed results demonstrating other macromolecules in the lumen of
      these organelles. Glycogen particles, which are known to be present within the
      lumen of the centriole/basal body of sperm cells, have now been found in basal
      bodies of protists belonging to three different groups. Here, we extend the
      debate on a role for RNA in basal body/centriole function and speculate on the
      origin and the function of centriolar glycogen.

PMID- 14731757
TI  - Annexins in membrane traffic.
AB  - Annexins have long been though to be involved in exocytosis, possibly by helping
      to create close interactions between membranes destined to undergo fusion. In
      this article, we examine recent observations that implicate annexins in three
      different steps of the endocytic pathway, suggesting that annexins may be
      universal modulators of membrane trafficking.

PMID- 14731758
TI  - The importance of G-protein beta lambda subunits.
AB  - As the properties of more and more isoforms of the molecules involved in G
      protein-mediated signal transduction pathways are unravelled, surprising
      diversity and versatility are being revealed. The path from receptor to effector
      is not dictated exclusively by the alpha subunits of heterotrimetric G proteins.
      The nature of the beta lambda subunit complex probably controls interactions of
      G(alpha) with receptors. In addition, dissociation of G(alpha)-GTP from G(beta
      lambda)provides two signalling complexes, and these proteins regulate effectors
      independently or synergistically. Synergistic or conditional regulation of
      effectors by G(alpha) and G(beta lambda)can provide a molecular signal that
      records the association of independent events.

PMID- 14731759
TI  - Structure, function and assembly of the nucleolus.
AB  - Most events of ribosome biogenesis--such as transcription of the ribosomal RNA
      (rRNA) genes, processing of their primary transcripts into mature rRNAs and
      assembly with ribosomal and nonribosomal proteins to form the preribosomes--are
      confined to a special nuclear compartment, the nucleolus. Immunogold labelling
      and in situ hybridization at the ultrastructural level are providing novel
      insights into structure-function relationships of the nucleolus, and in vitro
      systems are beginning to shed light on the molecular mechanisms involved in the
      reforming of nucleoli after mitosis.

PMID- 14731760
TI  - FRET for studying intracellular signalling.

PMID- 14731763
TI  - Patrilocal* cell-cell interactions: sevenless captures its bride.
AB  - Development of the R7 neuron in the compound eye of Drosophila requires an
      inductive interaction between the R8 photoreceptor cell and the bipotential R7
      precursor cell. Two transmembrane proteins mediate this induction: sevenless
      (sev), a receptor tyrosine kinase expressed on the apical surface of the R7
      precursor cell, and its ligand, the bride of sevenless protein (boss) on the
      apical membrane of the R8 neuron. The boss protein, with its large extracellular
      domain and seven transmembrane segments, is an unusual ligand for a receptor
      tyrosine kinase, and its internalization into the R7 cell following interaction
      with sev is particularly intriguing.

PMID- 14731764
TI  - New and cryptic biological messages from RNases.
AB  - RISBASEs are RNases with surprising biological actions, or unexpected
      physiological roles, in which they act as external factors that influence cell
      behaviour. There are RISBASEs involved in host defence, angiogenesis and the
      control of pollen fertility, and RISBASEs with antitumour and antispermatogenic
      actions. Here, Guiseppe D'Alessio describes these unusual roles for RNases, and
      speculates about the mechanisms underlying their actions.

PMID- 14731765
TI  - The membrane skeleton.
AB  - One important element that defines cell shape is the membrane skeleton. This
      filamentous network is closely apposed to the cytoplasmic face of the plasma
      membrane where it gives mechanical support to the membrane, provides specific
      attachment sites for cytoskeletal components and helps to organize some integral
      membrane proteins into domains. The membrane skeleton of erythrocytes has been
      studied extensively by biochemical and ultrastructural methods, but similar
      structures in other cell types are just beginning to be defined. In this review,
      David Pumplin and Robert Bloch draw attention to these nonerythroid skeletons and
      compare and contrast them with the erythrocyte model.

PMID- 14731766
TI  - Molecular components of the centrosome.
AB  - The centrosome organizes microtubules during both interphase and mitosis and
      therefore governs fundamental processes in the life of a eukaryotic cell. The
      past few years have seen a substantial increase in the identification of
      potential components localized at the centrosome. Although we are still far from
      achieving a coherent picture of the workings of the centrosome, these recent
      discoveries are promising first steps towards an understanding of centrosomal
      functions at the molecular level.

PMID- 14731767
TI  - Telomeres and the functional architecture of the nucleus.
AB  - The single molecule of DNA that constitutes a eukaryotic chromosome begins and
      ends with a stretch of repetitive DNA known as a telomere. These sequences appear
      to be necessary to preserve the integrity of the genetic material through the
      cell cycle. Telomeric DNA is organized into regions of non-nucleosomal chromatin
      called the telosome, which can interact with other telosomes and with the nuclear
      envelope. This review focuses on cytological evidence for these interactions and
      on recent insights into the molecular organization of the telomeric complex.

PMID- 14731768
TI  - Sorting out mitochondrial proteins.

PMID- 14731772
TI  - Potocytosis of small molecules and ions by caveolae.
AB  - Potocytosis is an endocytic process for concentrating and taking up small
      molecules and ions. The vehicle for internalization is the caveolae, a membrane
      specialization that has previously been implicated in membrane internalization.
      Within closed caveolae, the glycosylphosphatidylinositol-anchored class of
      membrane proteins generate high concentrations of small molecules or ions either
      by releasing receptor-bound species, by enzymatically converting abundant
      extracellular molecules, or by releasing them from a sequestered, soluble carrier
      protein. This pathway may also be involved in novel signal-transducing devices.

PMID- 14731774
TI  - A structural similarity between mammalian and yeast transcription factors for
      cell-cycle-regulated genes.

PMID- 14731773
TI  - A class of membrane proteins with a C-terminal anchor.
AB  - Integral membrane proteins are generally targeted to translocation-competent
      membranes by virtue of signal sequences located close to the N-terminus of the
      polypeptide chain. Membrane anchoring is caused by the signal sequence or other
      hydrophobic segments located after it in the amino acid sequence. However, some
      integral membrane proteins do not follow these rules. The members of one class of
      nonconformist membrane proteins have no signal sequence, but instead possess a
      hydrophobic segment near the C-terminus that orients them with their N-termini in
      the cytoplasm. Members of this class are found in many organelles and are
      probably inserted into membranes by an unusual mechanism.

PMID- 14731775
TI  - Buffers for cell culture.

PMID- 14731776
TI  - Bidirectional membrane traffic between the endoplasmic reticulum and Golgi
      apparatus.
AB  - Membrane traffic between the endoplasmic reticulum and Golgi apparatus is a
      highly regulated process that uses distinct anterograde and retrograde pathways.
      These pathways link two organelles that together function as a dynamic membrane
      system specialized for the biosynthesis and sorting of membrane to be used
      throughout the cell. The nature and underlying biochemical control of membrane
      transport along these pathways is thought to be tied to a common regulatory
      system involving assembly and disassembly of cytosolic proteins on membranes.

PMID- 14731777
TI  - Genetic approaches to studying peroxisome biogenesis.
AB  - How proteins are imported into peroxisomes is a question attracting considerable
      interest at present. Peroxisomal proteins, including the integral membrane
      proteins of the membrane bounding the peroxisome, are synthesized on free
      cytoplasmic ribosomes. They assemble post-translationally into pre-existing
      peroxisomes. New peroxisomes are believed to form exclusively by division of old
      ones. Few molecular details of this process have been elucidated so far, but
      genetic approaches are now beginning to identify the proteins catalysing
      peroxisome assembly.

PMID- 14731778
TI  - Dual roles for transcription and translation factors in the RNA storage particles
      of Xenopus oocytes.
AB  - During oogenesis, Xenopus laevis utilizes homologues of normal transcription or
      translation factors to sequester a variety of RNA molecules into
      ribonucleoprotein storage particles. This remarkable adaptive function for a
      diverse group of regulatory molecules allows the oocyte to stockpile
      macromolecules for use during embryogenesis. We discuss the special features of
      these nucleic acid-binding proteins and the insights into their structure and
      function that follow from their dual biological role.

PMID- 14731779
TI  - Merging minds on membrane merger.

PMID- 14731781
TI  - Maturation models for endosome and lysosome biogenesis.
AB  - The complexity and dynamic nature of the endocytic apparatus of mammalian cells
      have become increasingly clear over the past ten years. Structures collectively
      referred to as endosomes are at the crossroads of traffic with the plasma
      membrane and with the degradative pathway leading to lysosomes. They carry out
      the sorting and segregation of receptors and ligands, processes that are
      necessary for nutrient uptake and the maintenance of plasma membrane composition.
      This article addresses the question of whether endosomes are stable or transient
      compartments.

PMID- 14731794
TI  - Cell polarity and epithelial oncogenesis.
AB  - Pathologists have long recognized that tumour formation in epithelia leads to
      disruption of normal epithelial cell polarity. Despite this, few studies have
      taken advantage of new information on the biogenesis of cell polarity to analyse
      the process of epithelial oncogenesis. Recent studies of epithelial cell lines
      now indicate that the pattern of breakdown of polarity during oncogenesis may
      reflect the way in which normal epithelial cells achieve polarity. These results
      suggest not only a novel way to study the development of polarity in vitro, but
      also new ideas for the early detection of cancer.

PMID- 14731795
TI  - The kinesin superfamily: tails of functional redundancy.
AB  - Kinesin is a microtubule-based motility protein that mediates axonal transport
      and perhaps other intracellular movements in eukaryotic cells. Recent research
      has indicated that the principal component of kinesin, the kinesin heavy chain,
      is but one member of an extended superfamily of kinesin-like microtubule motor
      proteins. These proteins appear to have diverse microtubule-based motility
      functions--in mitosis, meiosis, vesicle transport and organelle transport. The
      various kinesin-like molecules may play overlapping or redundant roles in these
      processes.

PMID- 14731796
TI  - Protein import into mitochondria: two systems acting in tandem?
AB  - Mitochondria can import proteins from the cytoplasm at sites where the two
      mitochondrial membranes are closely apposed. However, each of these membranes
      contains a distinct protein translocation channel. Recent evidence suggests that
      the two types of channel are not permanently coupled, but may dissociate in a
      reversible manner. This reversible interaction is probably essential for
      intramitochondrial sorting proteins.

PMID- 14731802
TI  - The internal affairs of an integrin.
AB  - Integrins are adhesion receptors that exchange signals between the extracellular
      and intracellular compartments. From their cell surface transmembrane location,
      they interact with extracellular matrix ligands or cellular counter-receptors,
      translating external cues into signals that affect cytoskeletal organization,
      cell shape and motility. Conversely, intracellular events may modify the
      affinities of integrins for external ligands. Inside the cell, integrins connect
      with cytoskeletal structures that, until recently, were thought to be exclusively
      actin microfilaments. We comment on the case of the epithelial integrin,
      alpha(6)beta(4), which may instead interact with intermediate filaments. This
      integrin was recently shown by several laboratories to be part of the
      hemidesmosome complex, an epithelial adhesive structure that is the plasma
      membrane anchoring site for keratin-containing intermediate filaments.

PMID- 14731803
TI  - The arguments for pre-existing early and late endosomes.
AB  - The past decade has seen the elucidation of many of the events and processes
      responsible for receptor-mediated endocytosis. However, a fundamental question
      about the endocytic pathway remains unresolved: do early endosomes mature into
      late endosomes, or are these two distinct and pre-existing cellular organelles?
      General opinion tends to favour the former possibility, to the point where one
      poster session at the recent American Society for Cell Biology meeting was
      entitled 'Maturation of Endosomes'. This article draws together new data arguing
      in favour of pre-existing early and late endosomes, between which transport
      occurs by vesicle budding and fusion.

PMID- 14731804
TI  - Involvement of beta-COP in membrane traffic through the Golgi complex.
AB  - Non-clathrin-coated vesicles mediate membrane traffic through the Golgi complex.
      The proteins that constitute the coats of these vesicles have similar molecular
      weights to the clathrin coat proteins. A major component of the coat of non
      clathrin-coated vesicles, beta-COP, has significant homology with the clathrin
      coat protein beta-adaptin, indicating that the coats of the two different classes
      of vesicles may be structurally and functionally homologous.

PMID- 14731805
TI  - Pathways for the nuclear transport of proteins and RNAs.
AB  - The nuclear pore complex catalyses the import and export of both proteins and
      RNAs. The molecular mechanisms of RNA and protein translocation through the
      nuclear pore are likely to be similar; however, their signals and targeting
      apparatus may differ. Recent insights into RNA transport have come from studies
      of kinetic control mechanisms and the preconditions for translocation that
      include processing, RNP assembly, and a targeting function for 5' caps.

PMID- 14731806
TI  - Cytoplasmic dynein: advances in microtubule-based motility.
AB  - It is four years since the discovery that a cytoplasmic form of dynein was able
      to produce force along microtubules in the opposite direction to kinesin. Recent
      evidence has supported a role for this cytoplasmic dynein in retrograde organelle
      transport, as well as other forms of intracellular motility.

PMID- 14731807
TI  - Phospholipid transfer proteins: a biological debut.
AB  - Eukaryotic cells contain a battery of cytosolic proteins that catalyse
      phospholipid movement in vitro. Current studies are now revealing some surprising
      aspects of the in vivo function of such proteins, and are also uncovering
      previously unsuspected relationships between secretory pathway function,
      intracellular phospholipid transport, phospholipid biosynthesis, and the dynamics
      of the actin cytoskeleton.

PMID- 14731808
TI  - Secretory protein sorting, processing and granule biogenesis.

PMID- 14731812
TI  - The sticking point: How integrins bind to their ligands.
AB  - The integrin adhesion receptors are alpha beta heterodimers that exist in
      different ligand-binding states. Because of their large size and conformational
      lability, it has been difficult to determine how they interact with their
      ligands. Ligand-binding sites have been identified in the beta subunit, and now
      more recently in the 'I' domain and EF-hand-like domains V and VI of the alpha
      subunit. We speculate here about how these various sites might operate together
      to bind ligand in a stable manner.

PMID- 14731813
TI  - Neurotropic factors, retrograde axonal transport and cell signalling.
AB  - In vitro studies have recently identified receptors and signal transduction
      systems for many neurotrophic factors. In vivo, however, target-derived factors
      act over distances that are too great to be accounted for by simple diffusion of
      factors or classical second messengers. The active translocation of neurotrophic
      factors from the axon to the cell body by receptor-mediated retrograde transport
      provides a means by which factors presented at distal sites may influence somal
      signal transduction. We hypothesize that retrograde transport of receptors and
      other receptor-associated proteins leads to signalling at the cell body.

PMID- 14731814
TI  - Early pattern formation in the developing Drosophila eye.
AB  - The formation of complex cellular arrays from unpatterned epithelia is a
      widespread developmental phenomenon. Insights into the mechanisms regulating this
      transformation have come from studying the development of the Drosophila compound
      eye. Pattern formation in the eye primordium is a highly ordered process in which
      the onset of differentiation is coordinated with synchronization of cell cycle
      progression. Recent studies have identified a number of genes that are required
      for early patterning events, and provide a link between the regulation of
      proliferation and pattern formation.

PMID- 14731815
TI  - Essential genes that regulate apoptosis.
AB  - The expression of several genes has been associated with the induction of
      apoptosis in a wide variety of vertebrate and invertebrate organisms. However,
      relatively few gene products have been demonstrated to be required for cell
      death. This review highlights genes that are required for apoptosis and proposes
      mechanisms by which the proteins encoded by these genes might function.

PMID- 14731816
TI  - The Bcl-2 family of proteins: regulators of cell death and survival.
AB  - The Bcl-2 protein inhibits apoptosis induced by a variety of signals, in a range
      of cell types and in diverse organisms, and it is implicated in both normal
      development and oncogenesis. Despite this central role, the mechanism of action
      of Bcl-2 is not yet clear. Recent studies have uncovered a number of Bcl-2
      related gene products that regulate apoptosis either negatively or positively,
      and Bcl-2 forms heterodimers with at least one of these proteins, Bax. This
      article discusses the role of the Bcl-2 family of proteins in the light of these
      findings.

PMID- 14731817
TI  - Cycling with CDKs.

PMID- 14731821
TI  - Neurotransmitter release: fusion or 'kiss-and-run'?
AB  - The clear synaptic vesicles of neurons release their contents at the presynaptic
      membrane and are then quickly retrieved. However, it is unclear whether a
      complete cycle of exocytosis and endocytosis is always involved or whether
      neurotransmitter can be released by a transient interaction. Recent findings in
      chromaffin and mast cells suggest that exocytosis is preceded by the formation of
      a pore that has similar conductance properties to ion channels. The content of
      the secretory organelle partially escapes at this early step, but the pore can
      close before the vesicle fuses fully. This article looks at the evidence that
      quantal release of neurotransmitter from clear synaptic vesicles may occur by a
      similar 'kiss-and-run' mechanism.

PMID- 14731822
TI  - Migration of neutrophils through epithelial monolayers.
AB  - Acute bacterial infections are a major challenge to epithelial linings that
      interface indirectly with the external world. Such infections are in part fought
      by neutrophils, which phagocytose and destroy pathogens. Neutrophils arrive at
      the infection sites by emigrating from small blood vessels and subsequently
      interacting with and transmigrating across columnar epithelia. There is
      substantial interest in defining the mechanisms and functional consequences of
      neutrophil-epithelial interactions. Model systems reveal that specific molecular
      events are required for appropriate neutrophil-epithelial interactions and, as a
      result of these interactions, neutrophils may reversibly modulate diverse
      epithelial functions.

PMID- 14731823
TI  - Molecular biology of prion diseases.
AB  - What is the nature of the transmissible agent responsible for neurodegenerative
      diseases such as scrapie and mad-cow disease in animals and Creutzfeldt-Jakob
      disease in man? There is now weighty evidence that PrP(Sc), a modified version of
      the ubiquitously expressed host protein PrP(C), is responsible for pathogenesis
      of these diseases and that conversion of PrP(C) into PrP(Sc) under the influence
      of PrP(Sc) is the process leading to the propagation of PrP(Sc) and disease
      progression.

PMID- 14731824
TI  - The ins and outs of RB: coupling gene expression to the cell cycle clock.
AB  - Extracellular growth-stimulatory and -inhibitory signals govern the subunit
      assembly and activity of G1 cyclin-dependent kinases (cdks), which in turn can
      phosphorylate the retinoblastoma gene product, pRb, to cancel its growth
      suppressive function. Hypophosphorylated forms of pRb, present only during the G1
      phase, sequester target proteins including known transcription factors, but pRb
      phosphorylation late in G1 prevents these interactions and thus frees factors to
      alter the expression of genes required for entry into S phase. Although pRb can
      act as a regulator of the G1-S transition, its loss is tolerated by most cells,
      suggesting that its functions overlap with those of other regulators or are
      restricted to special circumstances under which cells exit the division cycle.

PMID- 14731825
TI  - The emerging family of dystrophin-related proteins.
AB  - Duchenne and Becker muscular dystrophies are caused by mutations in the gene
      encoding dystrophin, a component of the subsarcolemmal cytoskeleton. Dystrophin
      related proteins are identical or homologous to the cysteine-rich and C-terminal
      domains of dystrophin. This part of dystrophin binds to a membrane-spanning
      glycoprotein complex in muscle. At least five dystrophin-related proteins are
      encoded by the Duchenne muscular dystrophy locus. These proteins are found in
      many non-muscle tissues where dystrophin is not expressed and they are thought to
      be membrane-associated. Two other dystrophin-related proteins--utrophin and an 87
      kDa postsynaptic protein--are encoded by separate loci and, like dystrophin, they
      are components of the neuromuscular junction.

PMID- 14731826
TI  - DNA damage, repair and the cell cycle.

PMID- 14731827
TI  - Hiroshima welcomes gap junction communicants.

PMID- 14731833
TI  - The effects of HRT on screening mammography.
AB  - The effects of hormone replacement therapy on screening for breast cancer by
      mammography are reviewed. There is a decline in specificity in screen mammography
      for women over the age of 50 taking oral preparations, The use of HRT also
      reduces the sensitivity of breast screening by regular mammography.

PMID- 14731834
TI  - Mammographic screening under age 50: a review.
AB  - Trials indicate that screening women between 40 and 49 with mammography results
      in a clear mortality benefit. Whether this is worth the side-effects and
      financial cost is a matter of judgement. Some national health authorities and
      several other bodies consider the balance favourable enough to recommend general
      screening for this age group.

PMID- 14731835
TI  - The significance of histological determination of HER-2 status in breast cancer.
AB  - Since the identification of the novel transforming gene neu in rat neuroblastomas
      in 1981, and the subsequent cloning of the human equivalent HER-2, there have
      been considerable developments concerning the role and value of HER-2 in human
      breast cancer. Early studies found gene amplification in 20-30% of breast
      carcinomas, with most studies linking this to poorer survival. Numerous
      antibodies have been generated against the oncoprotein and in many instances
      overexpression, as defined by membrane staining of breast cancer cells,
      correlated with gene amplification. Many studies, but not all, have found an
      association between HER-2 reactivity and poor prognosis. HER-2 can also be
      detected in high-grade ductal carcinoma in situ. HER-2 status can also aid
      prediction of response to hormonal and chemotherapy, but the present interest
      lies in the humanized monoclonal antibody against HER-2 (Herceptin) that has been
      developed. This is only of value if there is over-expression of HER-2 by a breast
      cancer, and so a reliable, accurate method of determination of HER-2 status is
      required. Immunohistochemistry is widely used and is relatively simple, with no
      major equipment requirements. However, there are variations in results with
      different antibodies and standardized methods, with controls for evaluating
      extent of reactivity required. Fluorescent in situ hybridization, which detects
      gene amplification, is an alternative approach that can be used with fixed
      embedded tissue but the technique is less widely available. HER-2 is the first
      oncoprotein involved in breast cancer in which there has been direct translation
      from the laboratory to the patient.

PMID- 14731836
TI  - Introducing taxanes in the adjuvant treatment of breast cancer: expectations and
      reality.
AB  - Adjuvant chemotherapy in early breast cancer significantly improves disease-free
      and overall survival. However, a recent update of the world-wide overview
      indicated that improvements, though statistically significant, are of modest
      magnitude. Considering the results of individual clinical trials, further
      improvements in disease-free survival through introduction of new drugs as part
      of adjuvant treatment for breast cancer are expected to be small. Phase III
      studies in advanced, measurable disease, each involving several hundreds of
      patients, have been conducted with both paclitaxel and docetaxel and these
      results are now available. The high level of efficacy observed, especially with
      docetaxel, has led to their prompt introduction into adjuvant trials, and the
      results of one trial with paclitaxel are already available. In this trial, which
      included 3170 patients, paclitaxel was given every three weeks for four courses
      following an adjuvant treatment with four courses of doxorubicin and
      cyclophosphamide (AC) combination. The sequential use of the AC following by the
      taxane showed an early significant improvement of disease-free survival as
      compared to AC alone, but the difference observed was exclusively in the 40% of
      patients who had oestrogen receptor (OR)-negative disease. These patients, and a
      few of those with OR-positive primaries, did not receive tamoxifen following
      chemotherapy. Differences in duration of the entire adjuvant treatment programme
      might have influenced results leading to potentially the wrong conclusion being
      drawn that the taxane made the difference and other treatment variables had a
      negligible influence on outcome. Taxanes deserve a 'fair trial' in the adjuvant
      setting. Moreover, potential cardiotoxicity and long-term impact of high-dose
      steroids suggest that caution and longer follow-up are required before the
      definitive introduction of taxanes into the routine care of patients with early
      breast cancer.

PMID- 14731837
TI  - Sentinel node biopsy in breast cancer.
AB  - Axillary lymph node dissection (ALND) is an important tool in staging patients
      with breast cancer. However, this procedure has several sequelae and
      complications and improvement in early diagnosis has led to an increasing number
      of cases of ALND in which axillary nodes are found to be negative. Sentinel node
      (SN) biopsy appears to be a less invasive alternative to ALND. The aim of the
      present study was to assess whether SN is a reliable indicator for axillary
      staging. We studied 126 consecutive patients with T1-T2 breast cancer and
      clinically negative axilla. In each case, 30-70 MBq of 99mTC-labelled colloidal
      albumin was injected subdermally close to the tumour and SN was visualised by
      lymphoscintigraphy. Surgery was performed 24 h after injection and the SN was
      removed under the guidance of a gamma ray-detecting probe. ALND was then
      undertaken in all cases. A histopathologic examination of the SNs was then made
      and the findings compared with the status of the other axillary nodes. SNs were
      identified and biopsied in 115/126 patients (91.3%) and correctly predicted the
      axillary status in 110/115 cases (95.6%). In five cases (4.4%), SNs were found to
      be negative, but other axillary nodes were positive. Our data confirm that SN
      biopsy is a good method for staging the axilla in patients with breast cancer.
      However, before SN biopsy can replace ALND in daily clinical practice, some
      technical aspects must be standardized, and clinical trials are required in order
      to clarify the prognostic impact of false-negative cases.

PMID- 14731838
TI  - Aetiology of seroma formation in patients undergoing surgery for breast cancer.
AB  - Surgery for primary breast cancer and regional nodes often involves the use of
      suction drains post-operatively. It is believed that the fluid accumulating
      following axillary surgery is lymph from divided lymphatics or alternatively
      serum, although the composition of this fluid has never been studied in detail.
      Drain fluid following surgery for primary breast cancer was analysed for a number
      of haematological and biochemical parameters. Comparison of these values with
      plasma concentration produced a ratio that was compared with established lymph to
      plasma ratios. Haematological analysis indicates minimal contamination with
      blood. Comparison of drain fluid to plasma ratios with known lymph to plasma
      values for biochemical parameters showed that this fluid is compositionally
      different from lymph, but is similar to inflammatory exudate. Altering surgical
      technique to close dead space may avert the need for wound drainage, lead to
      reduced hospital stay and reduce the incidence of 'seroma' formation.

PMID- 14731839
TI  - Continuous infusional combination chemotherapy in inflammatory breast cancer: a
      phase II study.
AB  - Despite the introduction of systemic chemotherapy, inflammatory breast cancer
      (IBC) remains a disease with a poor prognosis. We performed this phase II study
      to evaluate the efficacy of infusional chemotherapy as initial treatment in
      patients with IBC. Fifty-four patients with newly diagnosed IBC were offered
      infusional chemotherapy and 34 accepted. The schedule consisted of continuous
      infusional ECF (bolus epirubicin and cisplatin, substituted by carboplatin or
      cyclophosphamide in some patients) plus continuous 5-FU, given three weekly for
      six cycles. Following chemotherapy patients went on to have surgery and/or
      radiotherapy. The chemotherapy was well tolerated and resulted in an overall
      response rate of 79% with 35% of patients achieving a complete clinical response.
      The median response duration, time to progression and overall survival were 12
      months (4-89+ months), 12 months (4-89+ months) and 23 months (7-89+ months),
      respectively. Patients had a 5 year disease free and overall survival of 11% and
      29%, respectively. Infusional ECF is well tolerated and achieves a high clinical
      response rate in patients with IBC, but survival results do not appear to be
      superior to those achieved with conventional bolus chemotherapy schedules.

PMID- 14731840
TI  - Thickened endometrium caused by tamoxifen returns to normal following tamoxifen
      cessation.
AB  - Endometrial thickening as seen on ultrasound scan of women on tamoxifen is well
      documented. To examine whether this phenomenon is reversible 20 women with
      thickened endometrium on scan but atrophic endometrium on further assessment
      underwent repeat ultrasound scan 6-11 months following tamoxifen cessation.
      Endometrial thickness reduced significantly in the majority of women off
      tamoxifen from a mean of 12.4 mm on tamoxifen to a mean of 7.8 mm off tamoxifen
      (P=0.0013).

PMID- 14731841
TI  - Chronic haematoma as a late complication of cosmetic breast augmentation.
AB  - To our knowledge, a chronic expanding haematoma has not been reported in a
      patient who received silicone gel breast prostheses for augmentation and never
      before at an interval as long as 12 years, as in our case. There have been
      occasional reports of chronic haematoma as complication of implantation of
      silicone breast prostheses after mastectomy for cancer, presenting 2.5-8 years
      later.

PMID- 14731842
TI  - Breast cancer at the end of a successful century: meeting highlights from the
      First Milan Breast Cancer Conference and discussion paper for the Second
      Conference (Milan, 14-16 June, 2000).

PMID- 14731843
TI  - 22nd annual San Antonio Breast Cancer Conference, Texas, USA, 7-11 December 1999.

PMID- 14731844
TI  - Cdc2 activation: the interplay of cyclin binding and Thr161 phosphorylation.
AB  - The mitotic kinase cdc2 must bind to a regulatory subunit--a cyclin--to be
      active. Cyclin binding controls the timing of activation of the kinase subunit,
      by modulating its interaction with upstream regulatory enzymes, and it also
      determines subcellular localization and substrate specificity. In this article, I
      summarize our present knowledge of the mechanisms that control cdc2 activation.

PMID- 14731845
TI  - Receptor-mediated regulation of constitutive secretion.
AB  - The traditional distinction between regulated and constitutive secretion may have
      contributed to the general belief that the latter is insensitive to extracellular
      modulatory signals. However, it now appears that signalling from membrane
      receptors can in fact modulate constitutive membrane traffic. In this article we
      discuss the molecular mechanisms, as well as the functional significance, of this
      modulation.

PMID- 14731846
TI  - Cellular substrates of p34(cdc2) and its companion cyclin-dependent kinases.
AB  - Cyclin-dependent kinase (cdks) are key components of the engine that drives the
      cell proliferation cycle in all eukaryotes. These kinases are related to
      p34(cdc2) and associate with regulatory subunits belonging to the cyclin family.
      To understand how cdks promote cell cycle progression, it will be important to
      identify their physiological substrates and to determine how phosphorylation
      influences the functions of these substrates. This article discusses recent
      progress as well as some of the problems related to the quest for cdk substrates.

PMID- 14731847
TI  - Cellular and molecular adaptations to injurious mechanical stress.
AB  - Transient disruptions of plasma membrane integrity--'wounds'--are frequently
      suffered by cells of gut, skin, muscle and the aorta, organs that are normally
      subjected to mechanical stress in vivo. As a protection against such potentially
      fatal mechanically induced injuries, cells may employ specialized submembranous
      proteins that mechanically reinforce the plasma membrane and thus prevent
      wounding or, should wounding occur, they may assemble a cytoskeletal structure to
      aid wound healing. Membrane wounds may provide a route out of the cytoplasm for
      basic fibroblast growth factor, explaining how a growth factor that lacks a
      conventional signal peptide sequence can act extracellularly.

PMID- 14731848
TI  - Plasmodesmata: the intercellular organelles of green plants.
AB  - Cytokinesis in higher plants results in the incomplete separation of daughter
      cells, due to the formation of special plasma-membrane-lined cytoplasmic bridges,
      called plasmodesmata. Within the green algae, these structures coordinate
      biochemical and physiological processes by facilitating the cell-to-cell
      diffusion of simple metabolites and ions. Until recently, most plant biologists
      thought that plasmodesmata perform a similar function in higher plants. However,
      it is now known that the more structurally advanced plasmodesmata of higher
      plants can also traffic macromolecules, including proteins and nucleic acids.
      These findings give new insights into how green plants evolved the ability to
      orchestrate their developmental and physiological processes in a supracellular
      rather than a multicellular manner.

PMID- 14731855
TI  - Golgi retention signals: do membranes hold the key?
AB  - The diverse forms and functions of cellular organelles are, presumably, a
      consequence of their particular molecular compositions. The generation and
      maintenance of this diversity is achieved by the targeting of newly synthesized
      proteins to specific locations and their subsequent retention there. Sequences
      that retain proteins in the endoplasmic reticulum (ER) have been identified at
      the C-termini of resident ER proteins, where they are readily accessible to
      potential receptors. By contrast, recent results have demonstrated that retention
      of proteins in the Golgi complex involves sequences located within transmembrane
      domains. This suggests the novel possibility that the membrane composition of the
      Golgi complex plays a role in retention of resident Golgi proteins.

PMID- 14731856
TI  - Basal bodies and DNA.
AB  - The possibility that basal bodies/centrioles contain nucleic acid has been a
      controversial topic in cell biology for several decades. These structures are
      conservatively replicated, are segregated at mitosis, and play a prominent role
      in cytoskeletal organization; thus, some have chosen to view centrioles as
      autonomous, self-replicating entities, and have searched for centriole-associated
      DNA. Two years ago, a report suggested that a chromosome defined by a specific
      linkage group is located within each basal body of the unicellular green alga
      Chlamydomonas. Several recent investigations have presented new data that force a
      re-evaluation of that conclusion.

PMID- 14731857
TI  - Oxygen radicals as second messengers.

PMID- 14731858
TI  - Protein translocation into the endoplasmic reticulum: a light at the end of the
      tunnel.
AB  - Intracellular transport of secretory of proteins and many membrane proteins in
      eukaryotic cells commences with their translocation into or across the membrane
      of the rough endoplasmic reticulum. Several components of the cellular machinery
      that mediates this process have been elucidated using in vitro assays or by
      genetic means. An analysis of how they function will depend on the ability to
      reassemble them into translocation-competent lipid vesicles.

PMID- 14731859
TI  - Organelle inheritance in the yeast cell cycle.
AB  - Cell proliferation requires the inheritance of subcellular organelles, yet little
      is known of the molecular basis of this essential process. Recent microscopy
      studies of the yeast Saccharomyces cerevisiae have characterized the cellular
      distribution of mitochondria, vacuoles and elements of the endoplasmic reticulum
      and Golgi complex. In addition, genetic and microscopical approaches have allowed
      the isolation and analysis of mutants defective in the inheritance of
      mitochondria and vacuoles. These investigations are leading to the identification
      of molecular components mediating the movement of organelles into daughter cells
      and have revealed that the inheritance of organelles is coordinated with other
      events of the cell division cycle.

PMID- 14731860
TI  - Vesicle budding: insights from cell-free assays.
AB  - Transfer of proteins and lipids between the various membrane-bound subcellular
      compartments of the eukaryotic cell is mediated by transport vesicles. The
      development of cell-free assays has allowed rapid progress towards a molecular
      description of the formation, or budding, of these vesicles. This article reviews
      and integrates data obtained from various yeast and mammalian systems on
      molecules involved in the budding reaction.

PMID- 14731861
TI  - Applications of confocal laser scanning microscopy.

PMID- 14731863
TI  - Nuclear pre-mRNA metabolism: channels and tracks.
AB  - We review new evidence suggesting that metazoan nuclear pre-mRNA metabolism
      occurs in a small subnuclear compartment consisting of a network of channels
      defined by exclusion from various condensed structures. Nuclear components,
      including mRNA en route from the gene to the nuclear surface, apparently move
      through these channels by conventional diffusion.

PMID- 14731864
TI  - The apoptosis endonucleases: cleaning up after cell death?
AB  - The term apoptosis describes the predictable structural changes associated with
      many forms of programmed cell death. One of the first visible events of apoptosis
      is the collapse of the nucleus. Nuclear degradation is manifested by digestion of
      chromatin into nucleosome-sized fragments or multiples of these. This digestion
      of DNA is enzymatic, and several attempts have been made to characterize
      apoptosis-specific endodeoxyribonucleases. Although there are strong candidates
      for such enzymes, direct evidence for their role in apoptosis is yet to be
      provided.

PMID- 14731865
TI  - Is there a role for GPIs in yeast cell-wall assembly?
AB  - Glycosylphosphatidylinositol (GPI) membrane anchors are essential for the
      integration of yeast cell adhesion proteins into the cell wall, but mature cell
      wall proteins are unlikely to be attached directly to the membrane. We thus
      propose that GPI-anchored glycoprotein forms are intermediates in a process that
      crosslinks the major components of the cell wall by transglycosylation. This
      mechanism may be critical for both the biosynthesis and overall architecture of
      the cell wall.

PMID- 14731866
TI  - Replication factories.
AB  - During S phase, DNA replication begins at numerous sites throughout the genome.
      Textbooks would have us believe that each replication fork tracks along the
      immobile DNA until it runs into the adjacent fork, but recent results question
      this view. Various studies show that replication forks are concentrated in
      immobile 'factory' units throughout the nucleus. Each factory contains as many as
      40 different replication forks and associated polymerases. These findings suggest
      that newly synthesized DNA is extruded as each template moves like a conveyor
      through the factory.

PMID- 14731867
TI  - Adenovirus entry into host cells: a role for alpha(v) integrins.
AB  - The mechanism(s) by which nonenveloped viruses enter host cells is poorly
      understood. The recent identification of cell-surface alpha(v) integrins as
      receptors for adenovirus internalization has shed much light on this process. In
      addition, analysis of alpha(v) integrins as internalization receptors for
      adenovirus has provided further insights into the biology of integrins.

PMID- 14731868
TI  - The unfolded-protein-response pathway in yeast.
AB  - The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers
      the increased production of several ER-resident proteins. This signalling pathway
      exists in organisms as divergent as mammals and yeast, and is the only known
      example of an intracellular signalling system that links the ER and the nucleus.
      Recently, a transmembrane kinase similar in structure to growth-factor receptor
      kinases has been identified as a key component of the unfolded-protein-response
      pathway in yeast.

PMID- 14731869
TI  - Tethering, targeting and triggering of protein phosphatases.

PMID- 14731879
TI  - The plant cytoskeleton-cell-wall continuum.
AB  - Two of the most challenging mysteries of morphogenesis are how cells receive
      positional information from neighbouring cells and how receipt of this
      information triggers events that initiate cell differentiation. The concept that
      the cytoskeleton and exocellular matrix' (ECM) form an interactive scaffold for
      perception and transduction of positional information is relatively new. Research
      is beginning to indicate that a continuous cytoskeleton-ECM scaffold may be a
      feature of all eukaryotic cells and that many of the molecules participating in
      this structure may be shared by plants, fungi and animals.

PMID- 14731887
TI  - Unusual routes of protein secretion: the easy way out.
AB  - Increasing numbers of polypeptides are being discovered that lack a cleavable
      hydrophobic signal sequence and are released from cells without passing through
      the classical secretory pathway. This article reviews the current knowledge of
      these alternative secretion pathways in prokaryotes and eukaryotes and discusses
      whether the mechanisms described in bacteria and yeast can be used as paradigms
      to explain unusual secretory phenomena in animal cells.

PMID- 14731888
TI  - Dynamic retention of TGN membrane proteins in Saccharomyces cerevisiae.
AB  - In a secretory pathway organelle like the Golgi complex, resident proteins are
      retained in the face of substantial protein flux to subsequent destinations.
      Recently, molecular genetic strategies have been used to study membrane protein
      retention in a compartment of the yeast Saccharomyces cerevisiae that is
      analogous to the trans Golgi network (TGN) of mammalian cells. These studies have
      defined retention signals containing aromatic amino acids in the TGN proteins'
      cytoplasmic domains. The identification of mutants that fail to retain TGN
      proteins has offered the first glimpse into the components involved in retention.
      The phenotypes of these mutants suggest that retention involves retrieval of TGN
      proteins from an endosomal compartment.

PMID- 14731889
TI  - Mitotic spindle pole separation.
AB  - Eukaryotic cells utilize a microtubular spindle to segregate chromosomes during
      mitosis. Chromosome segregation requires the timely separation of the mitotic
      spindle poles to which the chromosomes are attached. Recent studies at the
      molecular and cellular levels have provided new insights into the mechanism and
      regulation of this process. On the one hand, the process now seems more complex,
      as redundant mechanisms apparently overlap in function during cell division. On
      the other hand, some of these processes may be acting continuously during the
      various stages of spindle pole separation, suggesting an underlying simplicity.

PMID- 14731890
TI  - Assembly and transport of seed storage proteins.
AB  - Plant seeds store nitrogen by accumulating storage proteins in protein bodies
      within various compartments of the endomembrane system. The prolamin storage
      proteins of some cereal species are normally retained and assembled into protein
      bodies within the ER. Yet, these proteins lack a C-terminal KDEL/HDEL signal,
      suggesting that their retention is regulated by novel mechanisms. Furthermore, in
      other cereal species, such protein bodies formed within the ER may be
      subsequently internalized into vacuoles by a special route that does not utilize
      the Golgi complex. Thus, studies of the routing of seed storage proteins are
      revealing novel mechanisms of protein assembly and transport in the endomembrane
      system.

PMID- 14731891
TI  - The Balbiani ring particle: a model for the assembly and export of RNPs from the
      nucleus?
AB  - Balbiani rings are exceptionally large puffs on the polytene chromosomes in the
      dipteran Chironomus tentans. These puffs are particularly well suited for studies
      of the structure of active genes and the synthesis and transport of specific RNA
      protein (RNP) particles. The Balbiani ring RNP particle consists of a ribbon bent
      into a ring-like structure, the ribbon being built from a tightly folded 7 nm RNP
      filament. The assembly of the particle takes place concomitant with transcription
      and occurs in a stepwise fashion. As the particle is transported through the
      nuclear pore the ribbon straightens out, with the 5' end of the transcript
      leading. During translocation the tightly packed RNP filament is gradually
      unfolded, and on the cytoplasmic side the mRNA is immediately engaged in polysome
      formation.

PMID- 14731900
TI  - Nuclear protein accumulation by facilitated transport and intranuclear binding.
AB  - Nuclear proteins are transported from the cytoplasm into the nucleus via nuclear
      envelope pore complexes (NPCs). At the molecular level, the mechanisms
      responsible for this transport remain obscure. However, it is known that, for
      many proteins, the process requires ATP and proceeds against formidable
      nucleocytoplasmic concentration gradients. Therefore, the NPC is often thought of
      as an active transport site. In this article, Philip Paine presents the
      alternative hypothesis that, on current evidence, protein translocation across
      the nuclear envelope and accumulation in the nucleus can equally well be
      explained by facilitated transport through the NPC and subsequent intranuclear
      binding.

PMID- 14731901
TI  - Three clathrin-dependent budding steps and cell polarity.
AB  - Clathrin plays an important role in the vesicular transport of proteins in all
      eukaryotes, but the precise steps in which it is involved may not be identical in
      all of them. Here, I put forward the hypothesis that three distinct clathrin
      dependent budding events are common to all eukaryotes and have the following
      distinctive features: the first requires actin, the second is used for targeting
      soluble hydrolases from the Golgi to the hydrolytic compartment, and the third
      uses a tyrosine localization signal to concentrate membrane proteins. I suggest
      that the latter budding step is found on endosomes in yeast and is used for
      retrieval of membrane proteins back to the Golgi. Several testable predictions
      arise from this hypothesis as well as a possible evolutionary scenario concerning
      the origin of basolateral and apical plasma membranes in multicellular organisms.

PMID- 14731902
TI  - Protein translocation across membranes: common themes in divergent organisms.
AB  - Specific signal sequences are required for the translocation of proteins into and
      across both the endoplasmic reticulum of eukaryotes and the plasma membrane of
      prokaryotes. The similar properties of these signals, together with their ability
      to function when transferred between systems, suggested that the mechanisms of
      translocation in the two cases may be fundamentally similar. Indeed, recent
      findings have revealed striking similarities between essential components of the
      prokaryotic and eukaryotic translocation systems, suggesting that both are
      derived from a common ancestor.

PMID- 14731903
TI  - Gametophytic self-incompatibility: contrasting mechanisms for Nicotiana and
      Papaver.
AB  - Since Darwin first noted that not all plants produce self-seed, several
      mechanisms that regulate the acceptance or rejection of pollen during
      fertilization have been recognized, of which self-incompatibility (SI) is the
      most widespread. Over the past few years much progress has been made in
      understanding the molecular and cellular processes involved in SI. Here we review
      recent studies of the SI systems of Nicotiana alata and Papaver rhoeas. The SI
      systems are both determined by a single, multi-allelic gametophytically
      controlled S-gene, but involve quite different mechanisms.

PMID- 14731904
TI  - Nuclear RNA tracks: structural basis for transcription and splicing?
AB  - Knowledge of how the biochemical machineries governing metabolism and transport
      of several distinct classes of RNA may be organized and integrated into the
      structure of the nucleus remains very limited. Recent observations, including
      advances in the detection of specific nucleotide sequences directly within the
      nucleus, have heightened the long-standing interest in the structural
      organization of pre-mRNA transcription and processing.

PMID- 14731905
TI  - Unbiased 3-D quantitation of ultrastructure in cell biology.

PMID- 14731911
TI  - MAP kinase regulation--the oncogene connection.
AB  - The mitogen-activated protein kinase (MAP kinase) family of cytoplasmic
      serine/threonine protein kinases is activated by a wide range of extracellular
      stimuli. In this review we focus on the accumulating evidence that proteins
      encoded by proto-oncogenes and oncogenes are either involved in the regulation of
      the MAP kinase pathway or are its targets.

PMID- 14731912
TI  - Microtubule-bundling studies revisited: is there a role for MAPs?
AB  - The molecular mechanism of microtubule bundling has been enveloped in controversy
      for the past few years. At the centre of the debate are MAPs: are they necessary
      for the formation of microtubule bundles? In this article, Gloria Lee and Roland
      Brandt weigh the evidence and propose that microtubule stability might be the
      crucial factor in microtubule bundling. Perhaps then MAPs might act as spacer
      molecules between microtubules.

PMID- 14731924
TI  - Adaptins.
AB  - Clathrin has long been known to provide the structural basis for vesicle budding
      from the plasma membrane during endocytosis, but how is clathrin targeted
      specifically to some cellular membranes and not others? The answer seems to lie
      in the adaptors--protein complexes whose shape resembles the head of Mickey Mouse
      -which seem to be required both for clathrin-coat assembly and for sequestering
      specific receptors by interacting with their cytoplasmic domains. In this
      article, Margaret Robinson describes what is currently known about these
      versatile proteins.

PMID- 14731925
TI  - Early events in eukaryotic DNA replication.
AB  - Eukaryotic DNA replication is a tightly regulated process that occurs during a
      discrete period of the cell cycle known as S phase. Recent work in two different
      systems has identified key participants in this process and characterized many of
      the protein-protein interactions required for the establishment of functional
      replication complexes. From these results, an understanding of how the control of
      DNA replication is exercised during the cell cycle appears to be on the horizon.

PMID- 14731926
TI  - Transmembrane signalling by integrins.
AB  - Recent work has shown that integrin receptors serve not only as structural
      receptors that connect the extracellular matrix to the cytoskeleton, but also as
      signalling receptors that regulate intracellular pH, intracellular free calcium,
      phosphorylation of proteins on tyrosine and inositol lipid turnover. The ability
      of extracellular matrix to influence growth, differentiation and other cell
      functions is very likely related to their effects on signaling pathways inside
      the cell.

PMID- 14731930
TI  - Collaborative interactions between growth factors and the extracellular matrix.
AB  - The contribution of extracellular matrix (ECM) components to the regulation of
      cell adhesion, proliferation and differentiation is receiving much attention.
      Recently, it has become evident that certain cellular responses require the
      combined action of ECM components and soluble growth factors. This article
      examines possible mechanisms underlying the synergistic interactions of growth
      factors and the ECM.

PMID- 14731927
TI  - Intermediate filaments: not so tough after all.
AB  - The dynamic properties of cellular protein polymers such as microtubules and
      microfilaments depend to a large extent on the cell's capacity to modify rapidly
      the exchange rate between polymerized and unpolymerized pools of subunits. Until
      quite recently the dynamic nature of intermediate filaments was underestimated
      because of their biochemical stability in vitro and a paucity of studies on their
      characteristics in vivo. However, the recent studies described in this review
      show that the karyoskeletal and cytoskeletal structures that assemble from many
      intermediate filament proteins possess the properties expected of dynamic protein
      polymer networks.

PMID- 14731932
TI  - The bilayer couple hypothesis.

PMID- 14731931
TI  - Recognition domains in assembly of oligomeric membrane proteins.
AB  - Many integral membrane proteins, particularly receptors on the cell surface, are
      made up of several polypeptide chains. After translation and insertion into the
      ER membrane, these subunits must assemble into the mature protein. However, the
      mechanisms controlling their faithful assembly are largely unknown. Recent
      evidence has shed some light on two cell surface receptors that use different
      strategies to assemble their subunits. Zach Hall discusses oligomerization of the
      T-cell receptor and the acetylcholine receptor.

PMID- 14731934
TI  - Interpreting the effects of blocking PC biosynthesis.

PMID- 14731948
TI  - A proliferation of cyclins.
AB  - Cyclins are regulatory subunits of the serine/threonine protein kinases that play
      key roles in cell cycle control. The roster of known cyclins has expanded
      significantly in the past year, revealing a large and very diverse family of
      proteins. Although cyclins were originally characterized by their periodic
      accumulation during interphase and destruction in mitosis (these were the
      'mitotic' cyclins that control entry into mitosis), the newly identified cyclins
      do not conform to this pattern. Here we review what is known about the functions
      of the nonmitotic cyclins in yeast and in mammalian cells.

PMID- 14731949
TI  - New genes in the MHC that encode proteins for antigen processing.
AB  - Most cells process proteins into short peptides that are displayed on the cell
      surface bound to class I or class II proteins encoded by the major
      histocompatibility complex (MHC). These protein-peptide complexes can then be
      recognized by the circulating lymphocytes of the immune system. Several genes
      found recently in the MHC encode proteins with possible roles in the supply of
      peptides to class I molecules. The results imply that the peptides are produced
      in the cytoplasm by proteasomes and are translocated into the endoplasmic
      reticulum by 'peptide transporters' related to the multidrug resistance proteins.
      While there is little biochemical evidence to validate these ideas, Robert DeMars
      and Thomas Spies discuss here the arguments supporting this view. New data
      indicate that there may also be factors for class II peptide-processing hidden in
      the MHC.

PMID- 14731955
TI  - Cell cycle control of gene expression in yeast.
AB  - Increasing evidence suggests that cell-cycle-regulated gene expression plays a
      crucial role in cell cycle control. In building yeast, as many as 250 genes (3-4%
      of all genes in this yeast) may be regulated in this way. One large group is
      expressed at the G1-S transition and includes cyclin genes, whose products
      control the p34(CDC28) protein kinase, as well as many genes essential for DNA
      synthesis. Two separate systems control the expression of these genes in the late
      G1 phase, but these systems have in common the SW16 protein, which may be a cell
      cycle stage-specific transcription factor.

PMID- 14731956
TI  - Phosphatidyl-inositol 3-kinase: a key enzyme in diverse signalling processes.
AB  - Phosphatidylinositol (PI) 3-kinase associates in signal-transducing complexes
      with activated growth factor receptors and other protein tyrosine kinases. The
      enzyme may also act downstream of receptors that are not tyrosine kinases in
      terminally differentiated cells. The recent cloning of the catalytic subunit of
      PI 3-kinase has revealed a structural similarity to a yeast protein important in
      vacuolar protein sorting. This finding provides some interesting clues to the
      function of PI3-kinase in diverse cellular responses.

PMID- 14731957
TI  - An essential role for a protein and lipid kinase complex in secretory protein
      sorting.
AB  - Yeast genetics has identified more than 40 genes involved in the biogenesis and
      maintenance of the yeast lysosome-like vacuole. Recent data on two of these
      genes, VPS15 and VPS34, are beginning to provide some fundamental insights into
      the mechanisms governing protein sorting within the eukaryotic secretory pathway.
      VPS15 and VPS34 encode a novel protein kinase and a phosphatidylinositol 3
      kinase, respectively, that function together as components of a membrane
      associated signal transduction complex. These studies of the VPS15-VPS34 complex
      indicate that intracellular protein trafficking decisions may be regulated by
      protein phosphorylation and phosphatidylinositol signalling events.

PMID- 14731958
TI  - Protein export from the mitochondrial matrix.
AB  - Assembly of a functional mitochondrion requires import of proteins from the
      cytosol and export of proteins from the matrix. Most previous studies have
      focused on the import pathway followed by nucleus-encoded proteins. However, it
      is now clear that proteins encoded in the nucleus as well as those encoded in the
      mitochondrion also move from the matrix into and across the inner membrane, a
      process defined here as export. These exported proteins are found in at least
      three cellular locations: the inner mitochondrial membrane, the intermembrane
      space and the cell surface. Here, we consider the pathways for export and the
      relationships between import and export.

PMID- 14731959
TI  - Patches, posts and fences: proteins and plasma membrane domains.
AB  - Recent findings have indicated the presence of micrometre-scale protein-based
      domains in the membranes of several cell types. What are the implications of this
      organization for membrane function? Here, Michael Edidin describes the formation
      of protein-based domains, and discusses their possible effects on protein
      interactions within the bilayer.

PMID- 14731960
TI  - Targeting and fusion in vesicular transport.
AB  - Vesicular transport of proteins and lipids between distinct subcellular
      compartments is directly responsible for generating and maintaining the structure
      of the organelles of the secretory and endocytic pathways in eukaryotic cells.
      Rapid advances in a variety of experimental systems have resulted in the
      identification of molecules involved in late steps of the transport process. This
      article presents a general paradigm for vesicular fusion and reviews the
      available experimental evidence.

PMID- 14731965
TI  - Nuclear transport: a guide to import receptors.
AB  - After synthesis in the cytoplasm, nuclear proteins traverse the nuclear envelope
      as a result of the specific recognition of nuclear localization signals by
      import. Various approaches have now uncovered a range of proteins with at least
      some of the characteristics expected of import receptors. This article focuses on
      early steps in the nuclear import of proteins and surveys the recently identified
      candidate import receptors.

PMID- 14731966
TI  - The ANK repeat: a ubiquitous motif involved in macromolecular recognition.
AB  - Many proteins rely on stable, noncovalent interactions with other macromolecules
      to perform their function. The identification of a repeated sequence motif, the
      ANK repeat, in diverse proteins whose common function involves binding to other
      proteins indicates one way nature may achieve a wide range of protein-protein
      interactions. In this article, we describe evidence that these ANK repeats are
      involved in the specific recognition of proteins and possibly DNA, and present a
      model for the folding of the motif.

PMID- 14731967
TI  - Transepithelial transport and mucosal defence I: the role of M cells.
AB  - How do cells of the immune system encounter the majority of antigens that enter
      the body through the gut and airways? The epithelia lining these systems contain
      a remarkable cell type, the M cell, that delivers antigens across the epithelium
      to lymphocytes and macrophages. In this article, Marian Neutra and Jean-Pierre
      Kraehenbuhl describe the structure of the M cell, its function in promoting the
      immune response and its exploitation by invading pathogens. In the next issue of
      Trends in Cell Biology, these authors will review the other immunological
      function of epithelia, secretion of polymeric IgA.

PMID- 14731968
TI  - Cellular uptake and intracellular fate of antisense oligonucleotides.
AB  - Antisense oligonucleotides with sequences complementary to a given genetic target
      can enter cells in sufficient quantities to selectively inhibit gene expression.
      Thus, they have a potential therapeutic use in preventing undesirable gene
      expression in diseases such as cancer and AIDS. However, it is remarkable that
      these molecules, which have high molecular weights and are often charged, gain
      entry to cells at all. In this article, we review the possible mechanisms by
      which oligonucleotides enter cells and their subsequent intracellular fates. We
      also discuss current approaches for improving cellular uptake and delivery of
      antisense nucleic acids to their intended targets.

PMID- 14731969
TI  - Intracellular protein trafficking defects in human disease.
AB  - Secretory proteins and integral membrane proteins travel through the secretory
      pathway to a variety of destinations. Their targets are often specified by
      signals in the amino acid sequence or signals added post-translationally. The
      KDEL sequence that retains soluble proteins in the endoplasmic reticulum and the
      mannose 6-phosphate group of lysosomal enzymes are well-characterized examples of
      targeting signals; other signals are less well understood. Given the complexity
      and importance of the intracellular trafficking pathways, it is perhaps not
      surprising that mutations that affect the trafficking of proteins are associated
      with some human genetic diseases.

PMID- 14731972
TI  - Are casein kinases the assistant coaches for DNA metabolism?
AB  - A cell can be thought of as a well-coached sports team. To win, it needs
      superstar players with specialized tasks, but it also needs team players who can
      be relied on to maintain constant performance. Growth factor receptors or
      transcriptional activators might be considered to be the cell's superstars,
      whereas ribosomes could be considered team players that faithfully carry out
      directions from mRNA. The team also needs a head coach for overall direction and
      assistant coaches to direct the basic skills. The assistant coaches should ensure
      that basic cellular functions proceed correctly and that the cell responds to
      specific stimuli. Since almost every phosphorylatable protein is modified by
      several protein kinases, protein kinases like casein kinases I and II might be
      the assistant coaches of cellular regulation.

PMID- 14731984
TI  - Cell cycle control: many ways to skin a cat.
AB  - Thirty exponential cell divisions after fertilization would produce the number of
      cells in a baby mouse, but would not make a mouse. Sophisticated controls govern
      the cell cycle during development. These controls appear to play a central role
      in sculpting biological form. Rapid advances in our understanding of the
      machinery that drives the cell cycle provide a foundation for investigation of
      the molecular nature of cell cycle control in development. In this article, I
      emphasize that the design of the cell cycle machinery provides numerous inputs
      for regulation. I hope that the emphasis I have chosen will avert a tendency
      towards a narrow perception of cell cycle control.

PMID- 14731985
TI  - Tumour invasion: effects of cell adhesion and motility.
AB  - Metastasis is the major cause of failure in cancer therapy. Recent studies of the
      molecular cell biology of the metastatic process have provided new insights into
      the mechanisms of cell-cell adhesion, cell-substrate adhesion and cell motility
      that underly invasion by tumour cells. In this review, Van Roy and Mareel discuss
      the role of proteins with invasion-promoting and invasion-suppressing functions
      in metastasis.

PMID- 14731986
TI  - Transepithelial transport and mucosal defence II: secretion of IgA.
AB  - In this second article on mucosal defence and transepithelial transport, Jean
      Pierre Kraehenbuhl and Marian Neutra discuss the part played by a special class
      of antibody, polymeric IgA, in the protection of mucosal surfaces lining the
      digestive, respiratory and genital tracts, and the implications for mucosal
      vaccines. Polymeric IgA crosslinks luminal antigens or pathogens, thus preventing
      their interaction with epithelial cells. Following stimulation by antigen in the
      organized mucosal lymphoid tissue, effector B lymphocytes enter the circulation
      and migrate to distant mucosal or glandular sites, where they differentiate into
      polymeric-IgA-producing plasma cells. These antibodies reach the environment by
      transport across the epithelial cells of mucosal and glandular tissues.

PMID- 14731987
TI  - Calcium-binding proteins: beyond hands and loops.

PMID- 14731988
TI  - Counting cells with the new stereology.

PMID- 14731990
TI  - Ductal carcinoma in situ revisited.

PMID- 14731992
TI  - All women with breast conservation surgery for ductal carcinoma in situ should
      have radiation.

PMID- 14731991
TI  - The Consensus Conference on the Treatment of in situ Ductal Carcinoma of the
      Breast, 22-25 April 1999.

PMID- 14731993
TI  - Not everyone with ductal carcinoma in situ of the breast treated with breast
      preservation needs post-excisional radiation therapy.
AB  - While the results of NSABP protocol B-17 and EORTC protocol 10853 prove that
      radiation therapy decreases the overall rate of local recurrence in patients with
      DCIS, there are clearly subgroups of patients who do not benefit from radiation
      therapy or whose benefit is so small that the addition of radiation therapy to
      their treatment regimen is simply not worthwhile. Identifying these subgroups is
      of paramount importance. Factors like tumour size, margin width, nuclear grade,
      and the presence or absence of comedonecrosis can be used to define favorable
      subgroups that do not require post-excisional radiation therapy. The most recent
      results of NSABP protocol B-17 and EORTC protocol 10853 confirm that, regardless
      of treatment, there is no difference in the single most important end-point:
      survival. If there is no difference in breast cancer mortality, it is clearly
      worthwhile to try to define the subgroups of patients who can be spared the time,
      costs, and side-effects of a treatment that they do not need.

PMID- 14731994
TI  - The oestrogen receptors (ER alpha and ER beta) and their role in breast cancer: a
      review.
AB  - One of the main prognostic markers measured in breast tumours is oestrogen
      receptor (ER) status. With the discovery of ER beta, it has been necessary to re
      evaluate ER signalling and the role of ER in breast cancer. Preliminary reports
      on ER beta signalling suggest it might induce opposite effects to those of ER
      alpha. To further understand the biology of breast cancer, the role each ER plays
      in disease progression must be established. This review summarizes the current
      understanding of ER beta and discusses some of the published work on the role of
      ER alpha and ER beta in breast cancer.

PMID- 14731995
TI  - Are too many breast cancers missed at assessment?
AB  - Interval breast cancers presenting between screening episodes are an inevitable
      occurrence but their number should to be kept to a minimum. The objectives of
      this study were to ascertain the proportion of interval cancers developing in
      women who had been recalled for assessment after their initial screen and to
      review the assessment process. Interval cancers presenting after false negative
      assessment accounted for a small proportion (6%) but some cancers may have been
      diagnosed earlier if image guided FNAC or core biopsy had been included in the
      assessment process.

PMID- 14731996
TI  - Immunohistochemical assessment of oestrogen and progesterone receptors:
      correlations with the DCC method and clinical outcome in primary breast cancer
      patients.
AB  - Two different methods to determine steroid receptors were analysed with respect
      to their ability to estimate prognosis in primary breast cancer patients. The
      immunohistochemical assay (IHA) was compared with the dextran-coated charcoal
      (DCC) method of receptor determination. A random sample of 281 patients with
      invasive ductal carcinoma was drawn from 841 consecutive patients with primary
      breast carcinoma treated at Odense University Hospital between 1 January 1980 and
      31 December 1990. Receptor determination by the DCC method had been carried out
      previously in 164 patients for the oestrogen receptor and in 132 patients for the
      progesterone receptor. The former group was reassessed by IHA with the antibody
      ER1D5, and the latter with the antibody PgR-ICA. The median follow-up time was
      8.3 years (range 2.9-12.9 years). A cutoff of zero was used for the DCC method.
      Immunohistochemical results were quantified by counting in systematically random
      sampled fields of vision and values above zero were considered to be positive.
      Overall agreement of positive and negative cases was 86% for the oestrogen
      receptor and 83% for the progesterone receptor. Although the study included a
      limited number of patients, receptor positive cases fared better than negative
      cases in all situations. Investigation of the prognostic power revealed that
      classification based on IHA allowed better discrimination of patients than
      classification based on the DCC method. The reason for this difference might be
      because distinction between benign and malignant tissue is possible using the
      IHAmethod. Thus, IHAresults appear to be more clinically relevant.

PMID- 14731997
TI  - No useful role for fine needle aspiration as a marker for familial breast cancer.
AB  - A study of a single fine needle aspiration taken from the upper outer quadrant of
      228 asymptomatic women attending a family history clinic has been performed. No
      abnormalities were detected. This is not a useful screening tool in asymptomatic
      women at risk of breast cancer.

PMID- 14731998
TI  - The unusual mammographic appearance of breasts augmented by autologous fat
      injection.
AB  - We report the case of a woman presenting to our centre with two breast lumps, 12
      months after undergoing breast augmentation with autologous fat injection.
      Mammography showed a very unusual appearance, with most of the breast parenchyma
      displaced anteriorly by a large amount of fatty tissue. This was associated with
      extensive bizarre microcalcification, highlighting the difficulty in mammographic
      evaluation of this rare type of breast augmentation.

PMID- 14731999
TI  - Delay in the diagnosis of breast cancer: medico-legal implications.
AB  - Delay in the diagnosis of breast cancer is an important cause of medical
      malpractice claims which if trends continue, will threaten healthcare budgets.
      Most malpractice claims are made by younger women. Delay is most frequently due
      to the physician failing to be impressed with the clinical findings, or to a
      false negative mammogram report. Diagnosis of breast cancer is more difficult in
      younger women, because of the poor sensitivity of diagnostic tests and the high
      prevalence of benign disease in this age group. Models of tumour growth suggest
      that the potential to metastasize may be present before the tumour is clinically
      detectable and that if the growth rate of a given tumour is constant, any
      clinical delay is a small proportion of the lifespan of the tumour. Patient delay
      is generally associated with more advanced lesions at presentation, but the
      effect of delay on survival or what period of delay is significant remains
      uncertain. Delay in the diagnosis of breast cancer is likely to cause the patient
      considerable anxiety, especially when the public understands that the aim of
      mammographic screening is to diagnose breast cancer at an early stage in order to
      effect a cure. For a plaintiff to successfully claim in court she must prove that
      she has suffered an injury, and that the injury was the result of negligent
      medical practice. It is easier to defend a case of delay in diagnosis if the
      documentation is in order and all the appropriate tests have been performed.

PMID- 14732000
TI  - The influence of tamoxifen on serum triglycerides.

PMID- 14732001
TI  - Trimeric G proteins and vesicle formation.
AB  - Among the proteins regulating vesicular traffic, the small, Ras-like GTPases have
      received particular attention. Several recent reports indicate that another class
      of GTP-binding (G) protein, the heterotrimeric G proteins, also participates in
      the regulation of vesicular traffic. Thus, studies using transfected cells and
      cell-free systems show that a pertussis toxin-sensitive trimeric G protein,
      G(i3), is involved in the formation of secretory vesicles from the Golgi complex.
      These results raise the intriguing possibility that signal transduction processes
      across intracellular membranes play a role in vesicle formation, and provide
      important clues about the molecular machinery involved in this process.

PMID- 14732013
TI  - Ubiquitin-dependent protein degradation: a cellular perspective.
AB  - A major pathway for protein degradation in eukaryotes is ubiquitin dependent.
      Substrate-specific ubiquitin-conjugating enzymes and accessory factors recognize
      specific signals on proteolytic substrates and attach ubiquitin to defined lysine
      residues of substrate proteins. Ubiquitin-protein conjugates are then degraded by
      the proteasome, a multicatalytic protease complex. This proteolytic pathway is
      highly selective and tightly regulated. It mediates the elimination of abnormal
      proteins and controls the half-lifes of certain regulatory proteins. Targets
      include transcriptional regulators, p53 and cyclins, pointing to a role of the
      ubiquitin system in the regulation of gene expression and growth control.

PMID- 14732014
TI  - Regulating transcription factor activity by phosphorylation.
AB  - The initiation of transcription by RNA polymerase II is controlled by
      transcription factors. Changes in gene transcription are brought about by
      regulating the activity of these factors. Phosphorylation of transcription
      factors as a regulatory mechanism is both rapid and readily reversible.
      Furthermore, because a transcription factor can be targeted by many protein
      kinases and phosphatases, phosphorylation can effectively integrate information
      carried by multiple signal transduction pathways, thus providing opportunities
      for great versatility and flexibility in gene regulation.

PMID- 14732015
TI  - Antigen processing and presentation: close encounters in the endocytic pathway.
AB  - Stimulation of helper T cells by class II molecules occurs when the class II
      molecules bind and display peptides derived from foreign antigens that have been
      endocytosed. The formation of peptide-class II complexes requires antigen
      degradation and exposure of the peptide-binding site of class II molecules, both
      of which depend on proteolysis and low pH in the endocytic pathway. This review
      discusses the role of specific compartments of the endocytic pathway in the
      generation of antigenic peptides, and in the binding of antigenic peptides to
      newly synthesized class II molecules and those that are internalized from the
      cell surface.

PMID- 14732016
TI  - Optical tweezers in cell biology.

PMID- 14732022
TI  - Monoglucosylation of low-molecular-mass GTP-binding Rho proteins by clostridial
      cytotoxins.
AB  - Rho proteins, which are involved in receptor-mediated regulation of the actin
      cytoskeleton, are substrates for ADP-ribosylation by Clostridium botulinum C3
      toxins. Recently, it was shown that Rho and other members of the Rho subfamily of
      low-molecular-mass GTP-binding proteins are glucosylated by C. difficile toxins A
      and B. Glucosylation occurs at threonine-37, which is a crucial amino acid
      residue for the regulatory functions of the small GTP-binding proteins. These
      toxins should prove useful as tools for studying the functions of Rho proteins.

PMID- 14732023
TI  - Taking from the cytoplasm and giving to the pore: soluble transport factors in
      nuclear protein import.
AB  - The past year has seen the publication of a number of papers describing the
      identification of cytosolic factors involved in import of proteins to the
      nucleus. Although, at first glance, this gives the impression that the study of
      nuclear transport has become extremely complicated, these factors in fact form a
      relatively small group of proteins that have been given different names.
      Characterization of these proteins is improving understanding of the nuclear
      import process and provides a starting point for further investigation of the
      steps that occur at the nuclear pore complex.

PMID- 14732024
TI  - Functions of pRb and p53: what's the connection?
AB  - The pRb and p53 proteins have tumour suppressor functions and both are regulators
      of transcription. Their mechanisms of transcriptional regulation are unrelated in
      many ways--in contrast, it would appear, to their biological functions. This
      review highlights their biological connections in the light of recent advances in
      understanding the mechanisms of pRb and p53 function.

PMID- 14732029
TI  - Two-component signal-transduction systems in budding yeast MAP a different
      pathway?
AB  - Until recently, two-component signal-transduction pathways were thought to be
      exclusively found in bacteria. Some eukaryotic examples have now been
      characterized but, at least in the budding yeast Saccharomyces cerevisiae, it
      appears that this type of signal-transduction pathway is not utilized as
      extensively as in bacteria. Further, the few eukaryotic examples described
      suggest that two-component signal-transduction pathways might not be
      freestanding, as in prokaryotes, but might effect gene expression by regulating
      eukaryotic mitogen-activated protein (MAP) kinase pathways.

PMID- 14732030
TI  - The ins and outs of aggrecan.
AB  - Aggrecan is a large and highly complex macromolecule, uniquely structured to fill
      space in the extracellular matrix (ECM) of cartilage. Lethal chondrodystrophies
      resulting from mutations in the structural gene for aggrecan demonstrate the
      serious consequences of the absence of aggrecan. Other chondrodystrophies are
      testimony to the importance of post-translational modifications. Here, Barbara
      Vertel reviews the role of aggrecan in the ECM of cartilage, discusses genetic
      mutations affecting aggrecan and highlights intracellular features of its
      synthesis and processing.

PMID- 14732031
TI  - Compartmentalized signal transduction by receptor tyrosine kinases.
AB  - Signal transduction through receptor tyrosine kinases is believed to occur mainly
      at the plasma membrane. Ligands bind to their cognate receptors and trigger
      autophosphorylation events, which are detected by intracellular signalling
      molecules. However, ligands, such as epidermal growth factor and insulin, induce
      the rapid internalization of their receptors into endosomes. Although this event
      is traditionally thought to attenuate the ligand-induced response, in this
      article the authors discuss an alternative scenario in which selective and
      regulated signal transduction from receptor tyrosine kinases occurs within the
      endosome.

PMID- 14732033
TI  - Cell biologists can surf, too!

PMID- 14732032
TI  - Targeting the chromaffin cell.

PMID- 14732039
TI  - Entry of exogenous polypeptides into the nucleus of living cells: facts and
      speculations.
AB  - Although the plasma membrane acts as an impermeable barrier to most
      macromolecules, some exogenous proteins (for example fibroblast growth factor,
      HIV-1 Tat and lactoferrin) can gain access into the cytosol and reach the nucleus
      of living cells. How are these exogenous polypeptides selected over and above
      other extracellular proteins? How and where do they cross the cell membrane? Why
      do cells need to take up exogenous transcription factors when sophisticated
      signal-transduction pathways are available? Here, we review the current knowledge
      on these issues and discuss some mechanistic and physiological implications of
      this unconventional and direct way of taking messages to the nucleus.

PMID- 14732040
TI  - Mitotic disassembly of the mammalian Golgi apparatus.
AB  - A cell-free system that mimics mitotic fragmentation of Golgi stacks has provided
      a working model for the disassembly process. Two distinct pathways, one COP
      dependent and one COP-independent, act on Golgi stacks to give rise to two types
      of end products: transport vesicles and larger, more heterogeneous vesicles and
      tubules. We suggest that both mitotic end products result from enhanced fission
      of Golgi membranes under conditions where membrane fusion is generally inhibited.

PMID- 14732041
TI  - So it's cytosol!

PMID- 14732046
TI  - Laminin receptors: achieving specificity through cooperation.
AB  - The laminins are a large family of extracellular matrix proteins that can
      profoundly influence development, differentiation and disease progression. The
      biological effects of the laminins are mediated by surface receptors that link
      laminin matrices to intracellular signalling pathways. Several classes of
      receptors, including integrins and other molecules, may cooperate to provide the
      specificity apparent in the diverse array of laminin-mediated phenomena. This
      review assesses our current understanding of laminin receptors and discusses how
      such receptors could recognize structural differences among the laminins and
      relay these differences to the cell.

PMID- 14732047
TI  - Macropinocytosis.
AB  - Macropinocytosis is a form of endocytosis that accompanies cell surface ruffling.
      It is distinct in many ways from the better characterized micropinocytosis, which
      includes clathrin-coated vesicle endocytosis and small uncoated vesicles. Because
      macropinosomes are relatively large, they provide an efficient route for non
      selective endocytosis of solute macromolecules. This route may facilitate MHC
      class-II-restricted antigen presentation by dendritic cells. Because the ruffling
      that leads to macropinocytosis is regulated, it has been exploited by some
      pathogenic bacteria as a novel route for entry into cells.

PMID- 14732048
TI  - Make it or break it: the role of ubiquitin-dependent proteolysis in cellular
      regulation.
AB  - Effective regulation of the concentration of a protein in the cell requires rapid
      protein degradation. Until recently, it was widely believed that intracellular
      proteolysis was largely confined to the turnover of damaged, or otherwise
      abnormal, proteins. Recently, however, the role of protein degradation in
      cellular regulation has gained centre stage, and ubiquitin/proteasome-dependent
      proteolysis has been shown to play a key role in processes as diverse as
      embryonic development, transcription and the cell cycle.

PMID- 14732049
TI  - Peroxisomes proliferate.

PMID- 14732053
TI  - Inhibition of sphingolipid synthesis: effects on glycosphingolipid-GPI-anchored
      protein microdomains.
AB  - The idea that the transport and sorting of glycosylphosphatidylinositol (GPI)
      anchored proteins depends on their interaction with glycosphingolipids was first
      proposed five or six years ago. Until recently, only circumstantial evidence was
      available to support this suggestion. During the past year, compelling support
      for this hypothesis has been provided by observations that inhibition of
      sphingolipid synthesis reduces the rate of transport of GPI-anchored proteins in
      yeast, and abolishes the polarized sorting of a GPI-anchored protein in
      epithelia.

PMID- 14732054
TI  - Directionality in protein translocation across membranes: the N-tail phenomenon.
AB  - Protein translocation normally starts from an N-terminal signal peptide and
      proceeds in an N-to-C-terminal direction. However, in certain integral membrane
      proteins an N-terminal tail is translocated even though it is not preceded by a
      signal peptide. In eukaryotic cells this process involves the normal Sec
      machinery. In contrast, recent studies in Escherichia coli show that
      translocation of such N-terminal tails occurs by a mechanism that does not appear
      to involve the Sec proteins and is most efficient for short tails lacking
      positively charged residues. These novel observations suggest that the Sec
      machinery has an inherent N-to-C-terminal directionality and cannot work 'in
      reverse'.

PMID- 14732063
TI  - Two tumour necrosis factor receptors: structure and function.
AB  - Tumour necrosis factor (TNF) exerts two main effects: a beneficial one as an anti
      infection, anti-tumour cytokine, and a detrimental one in the systemic
      inflammatory response syndrome (SIRS). Two receptors (TNF-R) mediate these
      effects, but their precise role in different cell types is far from solved. TNF
      induces receptor oligomerization, an event that is believed to connect the
      receptors to downstream signalling pathways. Recent research suggests that
      several TNF-R-associated proteins, including kinases, may initiate cytoplasmic
      signal transduction.

PMID- 14732055
TI  - Theodor Boveri and the origin of malignant tumours.
AB  - As long ago as 1914, Theodor Boveri suggested that there is an inhibitory
      mechanism in every normal cell that prevents the process of cell division until
      the inhibition has been overcome by a special stimulus. From his work on abnormal
      mitoses in the eggs of echinoderms, Boveri also suggested that the inhibitor
      resided in the chromosomes. The relevance of Boveri's ideas to modern cancer
      research is discussed in this Retrospective article.

PMID- 14732064
TI  - The spermatid plasma membrane comes of age.
AB  - Spermiogenesis affords a unique opportunity to examine the formation of plasma
      membrane domains. Recent attempts to chart the life cycles of well-characterized
      integral plasma membrane proteins during spermiogenesis have suggested that
      spermatids are at least as adept as epithelial cells or neurons at establishing
      their plasma membrane domains. They appear to expand upon the standard recipe
      involving concurrent domain-specific protein targeting and diffusion barriers by
      using a combination of intracellular storage within the secretory pathway,
      developmentally-regulated delivery to provisional plasma membrane domains, large
      scale redistributions of diffusion barriers and integral plasma membrane
      proteins, and the shedding of an entire plasma membrane domain.

PMID- 14732065
TI  - Signal transduction in plants.

PMID- 14732068
TI  - Is NSF a fusion protein?
AB  - N-ethylmaleimide-sensitive fusion protein (NSF) is an ATPase required for
      vesicular transport throughout the constitutive secretory and endocytic pathways.
      Recently, NSF has also been implicated in regulated exocytosis in synapses--based
      on SNAP-mediated binding in vitro to a complex of neurotoxin substrates (termed
      'SNAREs'). This work has generated an hypothesis in which the interaction of
      SNAREs (SNAP receptors) on the vesicle membrane with those on the target membrane
      forms a docking complex to which SNAPs bind, thus allowing NSF to bind and elicit
      membrane fusion. However, current evidence supports an earlier, pre-fusion role
      for NSF. We speculate that this role may be as a molecular chaperone for the
      membrane docking/fusion machinery.

PMID- 14732069
TI  - A minimalist view of the secretory pathway in Plasmodium falciparum.
AB  - Would nature accept a eukaryotic cell that lacks a Golgi complex during a major
      part of its life cycle? Here, George Banting, Jurgen Benting and Klaus Lingelbach
      review recent morphological and biochemical data on the asexual intraerythrocytic
      stages of the protozoan parasite Plasmodium falciparum. They argue that these
      data may indicate that some stages of the life-cycle of this highly specialized
      organism lack a 'classical' Golgi complex.

PMID- 14732070
TI  - A novel viral homologue of Bcl-2 and Ced-9.

PMID- 14732077
TI  - Resolving the role of topoisomerase II in chromatin structure and function.
AB  - The catalytic activities of topoisomerase II are responsible primarily for
      solving the complex topological problems that arise from cellular processes such
      as DNA replication, transcription and chromosome segregation; however,
      topoisomerase II may also play a crucial structural role in the chromosome
      scaffold. Cell-cycle-regulated phosphorylation might be the key to these diverse
      functions. Phosphorylation of topoisomerase II might trigger the enzymatic
      activities essential for mitosis and promote interactions with specialized DNA
      sequences and other protein components of the eukaryotic chromosome to ensure the
      proper establishment and maintenance of chromatin architecture and function.

PMID- 14732078
TI  - Flippases.
AB  - A critical feature in the biogenesis of cellular membranes is the translocation
      (flipping) of phospholipids and glycolipids from one leaflet of a membrane
      bilayer to the opposing leaflet. In some cases, flipping results in a pronounced
      transbilayer lipid asymmetry which has important functional consequences. In
      general, flipping occurs only very slowly in artificial membranes but is
      accelerated to a biologically relevant rate in some biomembranes. Current data
      suggest that this acceleration is most likely brought about by protein catalysts
      (termed flippases). This article reviews available information on flippases,
      including the recent isolation of two flippases operating at the plasma membrane
      of animal cells.

PMID- 14732079
TI  - mRNA translocation and microtubules: insect ovary models.
AB  - The nurse cells in insect ovarioles supply the developing oocytes with various
      cellular components, including mRNAs, which pass from one cell to the other
      through intercellular bridges traversed by microtubules. Best studied of these
      mRNAs are those that encode the axis-determining factors in Drosophila embryos.
      These mRNAs are further translocated and localized within the oocyte to sites
      where the products of their translation will ultimately function. This article
      explores the evidence supportive of a role for microtubules and motor proteins in
      these processes.

PMID- 14732080
TI  - High-pressure freezing for cryoelectron microscopy.

PMID- 14732081
TI  - Molecular regulation of myelopoiesis.

PMID- 14732086
TI  - Time, telomeres and tumours: is cellular senescence more than an anticancer
      mechanism?
AB  - Normal diploid cells, by definition, have a limited life span: they senesce after
      a set number of divisions both in vivo and in culture. It has been hypothesized
      that the molecular mechanism that measures the life span of a cell probably
      involves the shortening of telomeres that occurs with each round of DNA
      replication. This loss of telomeres is thought to induce antiproliferative
      signals that result in the induction of cellular senescence. In this article,
      Woodring Wright and Jerry Shay present a hypothesis for the mechanisms by which
      telomere shortening regulates cellular physiology and argue that cellular
      senescence is not only an anticancer mechanism but is also the cause of many of
      the degenerative changes of aging.

PMID- 14732087
TI  - Chromosomes take the lead in spindle assembly.
AB  - Several kinesin-like motor proteins have recently been found associated with
      chromosome arms. They seem to be involved in the so-called 'polar ejection
      forces' that contribute to the congression of chromosomes on the metaphase plate,
      and at least one of them is essential for the maintenance of spindle bipolarity.
      The discovery of these molecules changes our view of the mechanism of spindle
      assembly and chromosome movement.

PMID- 14732088
TI  - Anterograde transport through the Golgi complex: do Golgi tubules hold the key?
AB  - Biochemical studies have suggested that anterograde protein transport through the
      Golgi complex is mediated by coatomer-coated vesicles that bud from one
      compartment and then transfer to, and fuse with, the next. However, recent
      genetic studies have shown that coatomer mutations block retrograde, but not
      anterograde, transport in yeast, calling into question the role of coatomer
      vesicles in anterograde transport. Peggy Weidman proposes that these findings
      might be explained if anterograde transport occurs by transient fusion of Golgi
      tubules and if coatomers have related, but separable, functions in tubule and
      vesicle dynamics.

PMID- 14732089
TI  - Anterograde transport of algal scales through the Golgi complex is not mediated
      by vesicles.

PMID- 14732090
TI  - Cytoplasmic or cytosolic?

PMID- 14732095
TI  - Regulation of calmodulin-binding myosins.
AB  - Myosins constitute a diverse superfamily of actin-based mechanoenzymes that are
      involved in many essential cellular motilities. In addition to conventional
      muscle myosin II, ten other classes of unconventional myosins are known. Many
      unconventional myosins bind multiple calmodulin light chains and Ca2+, which can
      dramatically alter their mechanochemical and enzymatic activity. Calmodulin
      binding myosins can also be regulated by phospholipid binding, phosphorylation of
      the heavy chain and actin-binding proteins. The molecular details linking
      unconventional-myosin regulation and function are just beginning to emerge.

PMID- 14732096
TI  - Microsomal triglyceride transfer protein: a protein complex required for the
      assembly of lipoprotein particles.
AB  - The mechanism of assembly of lipoprotein particles in the lumen of the
      endoplasmic reticulum is an important but poorly understood biological problem. A
      knowledge of this process is of great practical importance because possession of
      elevated levels of lipoproteins is one of the major risk factors for the
      development of atherosclerosis. This review describes a major advance in the
      delineation of the mechanisms involved in the assembly and secretion of
      apolipoprotein-B-containing lipoproteins: the demonstration of a requirement for
      microsomal triglyceride transfer protein.

PMID- 14732097
TI  - Ste5: a meeting place for MAP kinases and their associates.
AB  - Growth and differentiation of the budding yeast Saccharomyces cerevisiae is
      regulated by six functionally distinct but structurally similar MAP kinase
      cascades. Three of the protein kinases in the cascade that regulates G1-phase
      arrest and mating have recently been shown to form a multikinase complex with a
      LIM-domain-containing protein called Ste5. These studies implicate Ste5 as a
      tethering protein that physically links protein kinases operating sequentially in
      a cascade. The significance of this complex for the regulation and specificity of
      signal transduction is explored in this review.

PMID- 14732098
TI  - The basics of immunofluorescence video-microscopy for mammalian and microbial
      systems.

PMID- 14732101
TI  - Structural variations among the kinesins.
AB  - Members of the kinesin family of motor proteins are assembled from kinesin
      related polypeptides that share conserved 'motor' domains linked to diverse
      'tail' domains. Recent work suggests that tail diversity underlies the
      differences in quaternary structure observed among native kinesin holoenzymes.

PMID- 14732102
TI  - The microtubule lattice--dynamic instability of concepts.
AB  - In the February 1995 issue of trends in CELL BIOLOGY, Linda Amos presented her
      view of our current understanding of the lattice structure of microtubules, 20
      years after publication of the original paper describing the A- and B-lattices
      for flagellar microtubules. However, the question of the lattices of flagellar
      and cytoplasmic microtubules remains a matter for debate. In this article,
      Eckhard Mandelkow, Young-Hwa Song and Eva-Maria Mandelkow argue that the B
      lattice is predominant, implying structural asymmetry for most microtubules.

PMID- 14732103
TI  - A decade of kinesin, three decades of dynein.

PMID- 14732104
TI  - Tet-a-tet: a call for cells expressing the tetracycline-controllable
      transactivator.

PMID- 14732111
TI  - Chromatin organization re-viewed.
AB  - The predominant view of chromatin structure is that the beaded chain of
      nucleosomes is folded into a symmetrical helical fibre. Recently, however, direct
      evidence from cryoelectron microscopy and other imaging techniques confirms a non
      symmetrical organization, consistent with modelling based on the heterogeneity of
      linker DNA lengths. This mode of chromatin folding is more compatible with the
      range of functional states in the living nucleus.

PMID- 14732112
TI  - Nuclear migration advances in fungi.
AB  - Nuclear migration encompasses three areas: separation of daughter nuclei during
      mitosis, congress of parental nuclei before they fuse during fertilization, and
      positioning of nuclei in interphase cells. This review deals primarily with
      interphase nuclear migration, which is crucial for events as disparate as
      vertebrate embryonic development and growth of fungal mycelia. Mutants of
      Aspergillus nidulans, Neurospora crassa and Saccharomyces cerevisiae have been
      particularly informative, and a detailed molecular analysis of this process is
      now well under way.

PMID- 14732113
TI  - Microtubule-severing activity in M phase.
AB  - The stable cytoplasmic microtubules that emanate from centrosomes in eukaryotic
      cells disappear at the onset of M phase and are replaced by the dynamic
      microtubules of the mitotic spindle. Microtubule-severing activity increases
      significantly under the control of maturation-promoting factor at the transition
      between G2 phase and M phase, and is thought to be involved in the microtubule
      reorganization. This review highlights three microtubule-severing factors that
      may be responsible for microtubule-severing activity in M phase.

PMID- 14732114
TI  - Cell death comes to life in Purgatory: a Keystone meeting on apoptosis.

PMID- 14732117
TI  - Apoptosis: lessons from in vitro systems.
AB  - Although apoptosis is a major factor in metazoan morphogenesis and tissue
      homeostasis, its underlying biochemical mechanisms are poorly understood. This is
      now beginning to change as cell-free systems for the study of apoptosis start to
      reveal some of the activities involved. As suggested by earlier genetic analyses,
      a proteinase with properties resembling those of the interleukin-1-beta
      converting enzyme (ICE) has been shown to initiate the apoptotic cascade in
      vitro. Curiously, results obtained with the cell-free systems suggest that
      essential downstream effectors of the apoptotic response may be intrinsic
      components of healthy nuclei.

PMID- 14732126
TI  - Cell adhesion and signal transduction: the Armadillo connection.
AB  - The products of the Drosophila segment polarity gene armadillo and its vertebrate
      homologue beta-catenin are components of the signal transduction pathway for
      Wingless/Wnt-1; this signal regulates cell-fate choices in embryos of the fruit
      fly Drosophila and vertebrates. Armadillo/beta-catenin is also a component of
      cell-cell adherens junctions in epithelia. How can these two seemingly distinct
      roles be reconciled? Evidence suggests that Armadillo has distinct functions: one
      in the adherens junction and one or more in the cytoplasm. The biochemical role
      of Armadillo may be to serve as a scaffold upon which different multiprotein
      complexes are assembled.

PMID- 14732127
TI  - How can the products of a single gene be localized to more than one intracellular
      compartment?
AB  - Protein-targeting sequences are specific for each intracellular compartment, so
      that most proteins are found at only one location within the eukaryotic cell.
      Increasingly, however, examples are being found of proteins that occur and
      function in more than one cellular compartment. In some cases, the
      multicompartmentalized isoforms are encoded by the same gene. Several mechanisms
      have evolved to enable such genes to encode and differentially express multiple
      types of topogenic information. These mechanisms include alternative forms of
      transcription initiation, translation initiation, splicing and post-translational
      modification.

PMID- 14732128
TI  - The central region of the synaptonemal complex revealed in three dimensions.
AB  - The synaptonemal complex plays a key role in pairing of homologous chromosomes
      during meiosis. Its gross structure was already known by conventional electron
      microscopy, but only recently has it been possible to reveal the synaptonemal
      complex in three dimensions at higher resolution by electron microscope
      tomography. As the molecular analysis of meiosis is developing rapidly, a more
      thorough understanding of the principal organization of the synaptonemal complex
      is essential.

PMID- 14732130
TI  - Intracellular immunization: antibody targeting to subcellular compartments.

PMID- 14732129
TI  - Protein translocation across chloroplast envelope membranes.
AB  - Nuclear-encoded chloroplast proteins are imported from the cytosol into the
      chloroplast stroma by a common translocation machinery. Several components of the
      import apparatus, including GTP-binding proteins and Hsp70 proteins, have
      recently been identified and characterized. This review discusses the role of
      these proteins in chloroplast protein import.

PMID- 14732139
TI  - Kinetochores, microtubules and the metaphase checkpoint.
AB  - A decade ago, kinetochores were generally regarded as rather uninteresting
      structures that served only to attach mitotic chromosomes to microtubules. In the
      past few years, however, a number of experiments have belied this view and
      demonstrated that kinetochores are actively involved in moving chromosomes along
      the microtubules of the mitotic spindle. Now it appears that in addition to their
      function in motility, kinetochores act as dynamic and adaptable centres for
      regulating cell cycle progression through mitosis.

PMID- 14732140
TI  - Sphingomyelin synthesis in endosomal compartments?

PMID- 14732142
TI  - Less bulk, more flow: escape from the ER controversy.

PMID- 14732150
TI  - VE-DIC light microscopy and the discovery of kinesin.
AB  - Major advances in science are often tightly coupled with the development of new
      technology. The discovery of kinesin is an excellent example of this principle.
      The new technology was video-enhanced differential interference contrast light
      microscopy, which provided the enormous gain in image contrast needed to detect
      and measure kinesin-based motility in living cells, cell extracts and in vitro
      motility assays.

PMID- 14732151
TI  - A kinesin medley: biochemical and functional heterogeneity.
AB  - Over the past decade, a remarkable number and diversity of molecular motors have
      been described in eukaryotic cells. In addition to the identification of novel
      forms of myosin and dynein, the kinesins have been defined as an entirely new
      family of molecular motors. There may be as many as 30 different genes in a
      single organism encoding members of the kinesin superfamily. Why is such
      diversity in molecular motors needed? The biochemical and functional diversity of
      the originally defined form of kinesin provides some insights into the roles of
      molecular motors in cellular dynamics.

PMID- 14732152
TI  - Regulation of kinesin-directed movements.
AB  - Bidirectional organelle transport along microtubules is most likely mediated by
      the opposing forces generated by two microtubule-based motors: kinesin and
      cytoplasmic dynein. Because the direction and timing of organelle movements are
      controlled by the cell, the activity of one or both of these motor molecules must
      be regulated. Recent studies demonstrate that kinesin, kinesin-like proteins and
      kinesin-associated proteins can be phosphorylated, and suggest that changes in
      their phosphorylation state may modulate kinesin's ability to interact with
      either microtubules or organelles. Thus, it is possible that phosphorylation
      regulates kinesin-driven movements.

PMID- 14732153
TI  - Nanometres and piconewtons: the macromolecular mechanics of kinesin.
AB  - Much of our current understanding of the molecular physiology of kinesin has come
      from in vitro motility assays: indeed, the discovery of kinesin relied upon such
      assays. By marrying in vitro assays with novel instruments capable of resolving
      movements on the molecular scale, it has proved possible to make measurements on
      single motors. Such key parameters as the step size, stepping force, and force
      velocity relationship for kinesin have been determined in this fashion, and
      should soon contribute to a molecular model for the movement of kinesin.

PMID- 14732154
TI  - Four functions and a funeral: mitosis, replication, transcription, transport and
      apoptosis in the nucleus.

PMID- 14732160
TI  - Professional and non-professional phagocytes: an introduction.

PMID- 14732161
TI  - Phagocytosis by zippers and triggers.
AB  - Two mechanisms have been considered for particle phagocytosis. According to the
      zipper mechanism, ingestion occurs by sequential engagement of a phagocyte's
      membrane against the particle surface, and pseudopod advance proceeds no further
      than receptor-ligand interactions permit. In contrast, in the trigger mechanism
      particle binding initiates an all-or-none phagocytic response. Although the
      weight of experimental evidence has favoured the zipper mechanism, recent
      observations of bacterial entry into epithelial cells and macrophages indicate an
      indiscriminate, triggered response. This prompts a reconsideration of the
      underlying mechanisms.

PMID- 14732162
TI  - Signal transduction of phagocytosis.
AB  - The interaction of particles with certain cell surface receptors initiates
      intracellular signalling pathways that ultimately lead to submembranous actin
      filament assembly, pseudopod extension, and the ingestion of the particles. Here,
      Steven Greenberg reviews recent evidence implicating various signalling events in
      phagocytosis--in particular, activation of tyrosine kinases and
      phosphatidylinositol 3-kinase--and speculates how they might regulate the actin
      cytoskeleton.

PMID- 14732163
TI  - Membrane trafficking along the phagocytic pathway.
AB  - Phagosome maturation involves extensive remodelling of the phagosomal membrane as
      a result of intracellular transport events. Newly formed phagosomes exchange
      membrane-associated and soluble proteins with early endosomes by fusion. Budding
      of vesicles from the phagosome and fusion with Golgi-derived vesicles may also
      contribute to the remodelling of the phagosomal compartment. As a consequence of
      changes in membrane composition, phagosomes acquire the ability to fuse with late
      endocytic compartments. In vitro reconstitution and other studies suggest that
      the trafficking events underlying phagosome maturation require several GTP
      binding proteins, including Rab5 and Galphas', NSF-SNAP-SNARE complexes and
      coatomers.

PMID- 14732164
TI  - Phagocytic processing of antigens for presentation by MHC molecules.
AB  - Phagocytosis plays a major role in the defence of higher organisms against
      microbial infection not only by allowing ingested microbes to be destroyed by
      microbicidal mechanisms, but also by providing the basis for processing of their
      antigens to forms that generate immune responses. This article examines the role
      of the phagolysosome in antigen processing, and discusses the contributions of
      both MHC class II and MHC class I molecules to the presentation of antigens
      derived from phagocytosed material.

PMID- 14732165
TI  - Regulation of the phagocyte respiratory burst by small GTP-binding proteins.
AB  - Bacteria phagocytosed by leukocytes are killed and degraded by toxic oxygen
      metabolites produced in the phagosome via an NADPH oxidase. NADPH oxidase
      activity is regulated by small GTP-binding proteins in response to phagocytic
      stimuli. In this review, Gary Bokoch focuses on the role of Rac in regulating
      this important phagocytic process.

PMID- 14732166
TI  - Defensins in granules of phagocytic and non-phagocytic cells.
AB  - Antimicrobial proteins stored in lysosome-like granules of neutrophils and
      macrophages probably play an important role in killing phagocytosed microbes
      after delivery to the phagolysosome. Among the granules' antimicrobial
      armamentarium are defensins, peptides that kill a broad spectrum of
      microorganisms in vitro. Antimicrobial defensins were recently also isolated from
      non-phagocytic granulocytes of the mouse small intestinal epithelium, from where
      they are secreted into the lumen to function extracellularly. Clarification of
      the antimicrobial mechanisms of defensins in intracellular and extracellular
      environments will provide a key to understanding peptide-mediated host defence.

PMID- 14732167
TI  - The mechanism of phagocytic uptake promoted by invasin-integrin interaction.
AB  - Many pathogenic bacterial species produce factors that promote their
      internalization by host cells. The crucial components for uptake of one such
      pathogen, Yersinia pseudotuberculosis, have been identified. Efficient uptake of
      this microorganism requires tight binding of the bacterial invasin protein to
      integrins on the cell surface. Internalization also involves coordination of
      signals responsible for cytoskeletal rearrangements and those involved in
      receptor-mediated endocytosis. A start is being made to define the proteins that
      are required for efficient completion of the internalization process.

PMID- 14732168
TI  - Mycobacterium and Leishmania: stowaways in the endosomal network.
AB  - Microbial pathogens have evolved to exploit a wide range of niches inside the
      vertebrate host cell. Both Leishmania and Mycobacterium species remain within
      vacuoles following phagocytosis by their host's macrophages. Leishmania survives
      in acidic, lysosomal compartments, whereas Mycobacterium species limit the
      maturation of their phagosomes into hydrolytic lysosomes. Recent advances in our
      appreciation of the biology of these pathogens is providing unique insights into
      the normal conversion of phagosomes into lysosomes.

PMID- 14732169
TI  - Invasion of vertebrate cells by Toxoplasma gondii.
AB  - Toxoplasma gondii actively invades its host cell rather than entering by
      conventional phagocytosis. Invasion is powered by a microfilament-based motility
      system in the parasite that leads to invagination of the host cell plasma
      membrane to form a novel intracellular vacuole. This vacuole resists fusion with
      the endocytic network of the host cell and provides a protective environment for
      replication of the parasite.

PMID- 14732170
TI  - Lysosome recruitment during host cell invasion by Trypanosoma cruzi.
AB  - The protozoan parasite Trypanosoma cruzi uses an unusual mechanism to enter
      cells. Recent observations revealed that instead of trypanosomes being brought in
      to fuse with lysosomes, it is the lysosomes that migrate to the trypanosomes and
      actually participate in their internalization. Signalling events involving
      intracellular free Ca2+ occur upon contact of the parasites with host cells and
      may contribute to the regulation of this unusual process.

PMID- 14732171
TI  - Bacterial endosymbiosis in amoebae.
AB  - The large, free-living amoebae are inherently phagocytic. They capture, ingest
      and digest microbes within their phagolysosomes, including those that survive in
      other cells. One exception is an unidentified strain of Gram-negative, rod-shaped
      bacteria that spontaneously infected the D strain of Amoeba proteus and came to
      survive inside them. These bacteria established a stable symbiotic relationship
      with amoebae that has resulted in phenotypic modulation of the host and mutual
      dependence for survival.

PMID- 14732172
TI  - Phagocytosis of microbes: insights and prospects.

PMID- 14732173
TI  - P53 and breast cancer.
AB  - p53 mutation is the most common genetic abnormality found so far in human cancer,
      and in breast cancer p53 mutation/alteration is seen in up to 50% of primary
      carcinomas. Together with the increasing knowledge of the characteristics and
      understanding of the role of p53 over the last two decades, attention in recent
      years has been focused on how this knowledge can be used in clinical settings for
      patient care and management in terms of analyzing p53 as a potential marker for
      studying the relationship between p53 expression and tumour development,
      progression and outcome; and designing alternative treatment strategies
      specifically aimed at restoring normal p53 function.

PMID- 14732174
TI  - The management of familial breast cancer.
AB  - Epidemiological studies over the past several decades have consistently supported
      the concept that a proportion of breast cancers develop as the result of an
      inherited familial predisposition. However, until recently our understanding and
      knowledge of the underlying genetic processes involved have been limited. Current
      advances in molecular biology have shown that hereditary breast cancer may arise
      as the result of mutations of several specific gene loci including BRCA1, BRCA2,
      ATM gene, PTEN and p53. Several other less frequently occurring predisposition
      genes such as the androgen receptor gene (AR), the HNPCC genes and the oestrogen
      receptor gene may also be involved, but to a lesser extent. It is estimated that
      approximately 5-10% of all breast cancers involve one of these inherited
      predisposition genes, with BRCA1 and BRCA2 accounting for up to 90% of this
      group. Mutation analysis is complex in nature and is presently in a developmental
      and evolving phase, for which reason genetic testing should be offered on a
      selective basis and through genetic counselling clinics. This report reviews the
      current knowledge and roles of the various predisposition genes and discusses the
      management implications for both affected and nonaffected members of breast
      cancer families. Comprehensive and informative counselling is critical for women
      with an inherited predisposition to breast cancer and this has led to the
      evolution of familial cancer clinics involving a multi-disciplinary specialist
      team approach. Familial cancer clinics can provide individuals with information
      about their risk of developing breast cancer and offer advice regarding the
      various management options presently available.

PMID- 14732175
TI  - Role of thrombomodulin in cancer biology.
AB  - Effects of malignancy on haemostasis have long been recognized. The role of
      coagulation factors, anticoagulants and fibrinolytic agents in cancer biology
      have emerged more recently. Thrombomodulin is a naturally occurring
      anticoagulant, expressed by numerous epithelial and lymphovascular tumour cells.
      It may have a role in tumour metastasis.

PMID- 14732176
TI  - Hormone receptor status of breast cancer in India: a study of 798 tumours.
AB  - The objectives of this study were to document the oestrogen and progesterone
      receptor (ER & PR) status of breast cancer in the Indian population (as done by
      immunohistochemistry on paraffin blocks), and correlate the steroid receptor
      status of breast cancer with all relevant patient and tumour characteristics. Our
      current data have been compared with previously published data from other
      centres. In contrast to the higher rates reported in the Western literature, only
      32.6% of our tumours were ER positive and 46.1% were PR positive. Tumours were
      separated into four categories: ER+PR+ (25%), ER+PR- (7.4%), ER-PR+ (21.1%) and
      ER-PR- (46.5%). ER and PR immunoreactivity increased with advancing age, and
      correlated with the presence of elastosis. Infiltrating lobular carcinoma,
      mucinous carcinoma, and mixed tumours were more frequently ER & PR positive. High
      grade infiltrating duct carcinomas, pure comedo ductal carcinoma in situ, and
      medullary carcinoma were predominantly ER & PR negative. The presence of necrosis
      and lymphovascular invasion showed an inverse relationship with ER and PR
      reactivity.

PMID- 14732177
TI  - A randomized double blind-cross over trial of soya protein for the treatment of
      cyclical breast pain.
AB  - Twenty patients with cyclical breast pain were enrolled in a double-blind cross
      over trial in which either a soy protein drink or a flavoured cow's milk was
      taken orally each day for 3 months before crossing over to the alternate drink
      for a further 3 months. Records of pain scores were taken throughout the study.
      Blood was also taken before and after 3 and 6 months for the measurement of
      phytoestrogents to assess compliance. Two women withdrew from the study at the
      outset leaving 18 evaluable patients who completed the study. Of these 10 (56%)
      felt that soy protein improved breast pain (two of whom received soy as first
      treatment) and two (11%) felt that cow's milk alleviated symptoms (one receiving
      this as first preparation) and the remaining six (33%) experienced no relief of
      pain with either dietary preparation. Blood levels of diadzein and genistein were
      elevated after the ingestion of soy protein in only 13 patients (seven of whom
      felt that soy improved their breast pain); in the remaining five patients (three
      of whom suggested that soy protein improved breast pain) phytoestrogen levels
      were no higher than pretreatment values. Although the ingestion of soy protein
      may be associated with relief of breast pain, these results illustrate the
      problem of non-specific effects in studies of mastalgia in that 1) cow's milk
      also relieved breast pain in some patients and 2) that the benefits of soy
      protein were not always associated with evidence of elevated circulating levels
      of phyto-estrogens, indicating the difficulty of compliance in dietary
      intervention studies using soy foods.

PMID- 14732178
TI  - The predictive of tumour markers CA 15-3, TPS and CEA in breast cancer
      recurrence.
AB  - The predictive values of tumour markers Carcinoma-Associated Antigen CA 15-3,
      Tissue Polypeptide Specific Antigen (TPS) and Carcinoembryonic Antigen (CEA) in
      recurrence of breast cancer are unclear. The aim of this study was to examine the
      predictive value of these markers in our population of 1448 patients with
      diagnosed breast cancer. Data and mean follow-up of 4.4 years were available on
      1082 women of whom 277 had documented recurrence (mean follow up 5.7 years). The
      recurrence free patients had a mean follow up of 3.9 years. The sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      of CA 15-3, TPS and CEA for visceral, bony and locoregional recurrence were
      calculated. CA 15-3 was the most sensitive marker, 68% for visceral and 69% for
      bony recurrence. This compared with TPS, 64% and 51% and CEA, 27% and 46% for
      visceral and bony recurrence respectively. The positive predictive value of CA 15
      3 at 47% for visceral and 54% for bony recurrence was greater than that for TPS
      (visceral 25%, bony 21%) or CEA (visceral 18%, bony 26%). The sensitivity of CA
      15-3 and TPS for locoregional recurrence was low at 23% and 17% respectively. A
      combination of CA 15-3, TPS and CEA failed to increase the sensitivity of CA 15-3
      for visceral recurrence. However, a marginally increased sensitivity was recorded
      for combined CA 15-3 and TPS (70%) and for combined CA 15-3, TPS and CEA (71%) in
      bony recurrence. The mean lead time effect in visceral recurrence for TPS and CA
      15-3 were 8 and 10 months respectively. In patients with bony recurrence the mean
      lead time effect for TPS and CA 15-3 were 7.5 and 8.25 months. Mean lead time
      effect was increased to 9 and 11 months for bony and visceral recurrence
      respectively when CA 15-3 and TPS were combined. CA 15-3 remains the most
      sensitive tumour marker in breast cancer follow up with a significantly greater
      positive predictive value when compared to TPS or CEA. Both TPS and CEA failed to
      complement the sensitivity of CA 15-3 when measured in combination.

PMID- 14732179
TI  - Expression patterns of biologic markers in small breast cancers and preneoplastic
      breast lesions.
AB  - When does proliferating breast epithelium turn malignant? Single parameter
      analyses have not answered this question. We have tried to answer this through an
      analysis of immunohistochemical staining patterns in the following
      morphologically defined breast lesions: atypical ductal hyperplasia (ADH, 23
      cases), papilloma (12 cases), ductal cancer in situ (DCIS, 28 cases), and
      mammographically detected small primary cancers (34 cases). The seven antibodies
      used were c-neu, bcl-2, p53, p21, CD44, MIB 1, and FAS. Staining patterns were
      compared within groups and between groups of lesions. Interesting differences in
      staining patterns were seen between invasive ductal cancer and invasive lobular
      cancer: invasive lobular cancer was less p53-positive and more CD44-positive than
      invasive ductal cancer. We found no common pattern in the different proliferating
      epithelia to show when they become malignant.

PMID- 14732180
TI  - Immunohistochemical detection of a germline BRCA1 mutation in a breast and
      ovarian cancer family.
AB  - Tumours from four individuals in a breast and ovarian cancer family with a known
      deleterious germline BRCA1 mutation, were analyzed using BRCA1 antibodies. In
      addition, we examined tumours from 96 female patients with early-onset breast
      cancer, who were not selected because of any family history. Paraffin-embedded
      tumour sections were examined by standard immunohistochemical analysis. Three
      familial tumours from BRCA1 carriers displayed focal negativity. This observation
      was not seen in a non-mutation carrier from the same family. It was found that
      9/96 (9%) early-onset breast tumours had total BRCA1 negativity. In addition, 2/2
      (100%) medullary breast carcinomas displayed negativity for both antibodies. Our
      results indicate that BRCA1 antibodies can discriminate between familial tumours
      with and without a deleterious mutation from one family. Further mutation studies
      in early-onset breast cancer group will be necessary to evaluate the use of
      immunohistochemistry as a rapid, initial screening technique to identify BRCA1
      mutations.

PMID- 14732181
TI  - Surgeon General's commentary: CDC Multisite Violence Prevention Project:
      evaluating the prevention of youth violence.

PMID- 14732182
TI  - The multisite violence prevention project: background and overview.
AB  - This paper provides an overview of the Multisite Violence Prevention Project, a 5
      year project to compare the effects of a universal intervention (all students and
      teachers) and a targeted intervention (family program for high-risk children) on
      reducing aggression and violence among sixth graders. First, the paper describes
      the role of the Centers for Disease Control and Prevention in developing the
      project. Second, it details the background of researchers at the four
      participating universities (Duke University, The University of Georgia,
      University of Illinois at Chicago, and Virginia Commonwealth University) and
      examines the characteristics of the selected schools (n=37). Finally, the paper
      summarizes the theoretical perspectives guiding the work, the development of
      interventions based on promising strategies, the decision to intervene at the
      school level, the research questions guiding the project, the research design,
      and the measurement process for evaluating the results of the program.

PMID- 14732183
TI  - The study designed by a committee: design of the Multisite Violence Prevention
      Project.
AB  - This article describes the research design of the Multisite Violence Prevention
      Project (MVPP), organized and funded by the National Center for Injury Prevention
      and Control (NCIPC) at the Centers for Disease Control and Prevention (CDC).
      CDC's objectives, refined in the course of collaboration among investigators,
      were to evaluate the efficacy of universal and targeted interventions designed to
      produce change at the school level. The project's design was developed
      collaboratively, and is a 2 x 2 cluster-randomized true experimental design in
      which schools within four separate sites were assigned randomly to four
      conditions: (1) no-intervention control group, (2) universal intervention, (3)
      targeted intervention, and (4) combined universal and targeted interventions. A
      total of 37 schools are participating in this study with 8-12 schools per site.
      The impact of the interventions on two successive cohorts of sixth-grade students
      will be assessed based on multiple waves of data from multiple sources of
      information, including teachers, students, parents, and archival data. The
      nesting of students within teachers, families, schools and sites created a number
      of challenges for designing and implementing the study. The final design
      represents both resolution and compromise on a number of creative tensions
      existing in large-scale prevention trials, including tensions between cost and
      statistical power, and between internal and external validity. Strengths and
      limitations of the final design are discussed.

PMID- 14732184
TI  - Choosing to be violence free in middle school: the student component of the GREAT
      Schools and Families Universal Program.
AB  - This paper describes the theoretical basis and content of the universal student
      component of the Guiding Responsibility and Expectations for Adolescents for
      Today and Tomorrow (GREAT) Schools and Families' middle school violence
      prevention program for changing school climate. The GREAT Student Program builds
      on and extends the content of the sixth grade Responding In Peaceful and Positive
      Ways (RIPP-6) social-cognitive violence prevention program through an expanded
      conceptual framework that focuses on changing school norms and explicitly
      incorporates cultural and contextual goals. The program consists of twenty 40
      minute lessons taught by a trained facilitator on a weekly basis during the
      school day.

PMID- 14732185
TI  - A teacher-focused approach to prevent and reduce students' aggressive behavior:
      the GREAT Teacher Program.
AB  - The purpose of this article is to describe the GREAT (Guiding Responsibility and
      Expectations for Adolescents for Today and Tomorrow) Teacher Program, a
      prevention program for middle school teachers to deter students' aggressive
      behavior. It was developed on the basis of an ecologic understanding of
      aggression and on specific constructs of Social Cognitive Theory. The goals of
      the program were (1) to increase teacher awareness of different types of
      aggression, risk factors, role of the classroom teacher, and influence of the
      school climate on the child's behavior; (2) to develop strategies that will
      prevent aggression; (3) to improve teacher management skills to reduce power
      struggles and aggression; and (4) to enhance skills to assist students who are
      the targets of aggression. To accomplish these goals, teachers participated in a
      12-hour workshop and 10 support group sessions. Training, manuals, and
      supervision were provided to maintain program integrity and to assure the quality
      of implementation.

PMID- 14732186
TI  - Community-Based multiple family groups to prevent and reduce violent and
      aggressive behavior: the GREAT Families Program.
AB  - This paper describes the targeted intervention component of GREAT Schools and
      Families. The intervention-GREAT Families-is composed of 15 weekly multiple
      family group meetings (e.g., 4-6 families per group) and addresses parenting
      practices (discipline, monitoring), family relationship characteristics
      (communication, support, cohesion), parental involvement and investment in their
      child's schooling, parent and school relationship building, and planning for the
      future. High-risk youth and their families-students identified by teachers as
      aggressive and socially influential among their peers-were targeted for inclusion
      in the intervention. The paper describes the theoretical model and development of
      the intervention. Approaches to recruitment, engagement, staff training, and
      sociocultural sensitivity in work with families in predominantly poor and
      challenging settings are described. The data being collected throughout the
      program will aid in examining the theoretical and program processes that can
      potentially mediate and moderate effects on families. This work can inform us
      about necessary approaches and procedures to engage and support families in
      efforts to reduce individual and school grade-level violence and aggression.

PMID- 14732187
TI  - Evaluating the impact of interventions in the Multisite Violence Prevention
      Study: samples, procedures, and measures.
AB  - This paper discusses the procedures and measures that were developed and utilized
      to evaluate the impact of the GREAT (Guiding Responsibility and Expectations in
      Adolescents Today and Tomorrow) programs in the Multisite Violence Prevention
      Project (MVPP). First, we describe the three different samples used to examine
      the impact of the programs, and the different sources of data used to assess
      these samples. Next, we outline procedures used to collect and manage the data.
      In the last section, we summarize the final set of measures selected for use in
      this study. Throughout the paper, we highlight ways in which the participating
      institutions collaborated to develop consistent procedures for use across the
      four sites. Overall, the paper provides important information related to the
      evaluation of violence prevention efforts, particularly for working effectively
      in multisite collaborative studies.

PMID- 14732188
TI  - Lessons learned in the Multisite Violence Prevention Project collaboration: big
      questions require large efforts.
AB  - This paper summarizes some organizational, scientific, and policy lessons that
      have emerged in the formation and conducting of the collaboration of the
      Multisite Violence Prevention Project. We contend that these lessons are valuable
      for other collaborations and are important for furthering the utility of
      scientific efforts. A central contention is that large-scale efforts such as this
      collaboration are underused but are essential for efficient advancement of
      knowledge about preventing youth violence.

PMID- 14732189
TI  - A view from the front lines: implications of the Multisite Violence Prevention
      Project for violence prevention at state and local health departments.

PMID- 14732190
TI  - Supporting violence prevention at the school site: issues and lessons in state
      administration.

PMID- 14732191
TI  - The Multisite Violence Prevention Project: a commentary from academic research.

PMID- 14732194
TI  - A radical idea: men and women are different.

PMID- 14732195
TI  - Growth hormone-releasing peptides and the heart: secretagogues or
      cardioprotectors?

PMID- 14732196
TI  - Why shocking might be not shocking enough.

PMID- 14732197
TI  - The ubiquitin-proteasome system in cardiovascular diseases-a hypothesis extended.
AB  - During recent years, the ubiquitin-proteasome system has become known as the
      major pathway of non-lysosomal degradation of intracellular proteins, involving
      two sequential steps. In the first step, multiple moieties of ubiquitin are
      covalently bound to target proteins to be recognized and degraded by the multi
      enzymatic proteasome complex in the second step. In addition to the elimination
      of damaged and unneeded proteins, this system fulfills an important function in
      the regulation of cellular mediators in various biological pathways. Foremost,
      these biological pathways include inflammation, cell proliferation, and
      apoptosis, all of which constitute important characteristics of atherosclerosis.
      Indeed, recent experimental evidence supports a potential involvement of the
      ubiquitin-proteasome system in the initiation, progression, and complication
      stage of atherogenesis. This review summarizes recent findings regarding the
      ubiquitin-proteasome system in cardiovascular diseases and discusses the
      potential use of proteasome inhibitors in cardiovascular therapy.

PMID- 14732198
TI  - Gender differences in superoxide generation in microvessels of hypertensive rats:
      role of NAD(P)H-oxidase.
AB  - OBJECTIVE: This study is aimed to explore whether gender plays a role in the
      generation of nitric oxide (NO) and superoxide anion (O(2)(-)) in microvessels of
      hypertensive rats (SHR), as well as the potential mechanisms involved in these
      effects. METHODS AND RESULTS: NO generation in mesenteric arterioles was
      evaluated by measuring NO synthase (NOS) activity and protein expression.
      Oxidative stress was studied in vivo in mesenteric arterioles from male and
      female SHR by hydroethidine microfluorography. Although we did not observe any
      sex-related differences in NO generation, we found that hydroethitine oxidation
      is markedly increased (30.9+/-2.4%) in male compared to female (12.3+/-2.5%;
      p<0.05), demonstrating a gender difference in O(2)(-) production. The treatment
      of mesenteries with DPI (NAD(P)H-oxidase inhibitor) and treatment of SHR with
      losartan [Angiotensin-II type 1 (AT-1) receptor antagonist] markedly reduced
      O(2)(-) production in male, while produced a minor effect in female, suggesting
      that overexpression/activity of AT-1 receptor and NAD(P)H-oxidase contribute for
      the sexual dimorphism in superoxide generation. Immunoblot analyses provide
      evidences of overexpression of the NAD(P)H-oxidase components p22(phox),
      gp91(phox), p47(phox) and p67(phox) in arterioles from male in comparison to
      female. Losartan treatment inhibited the overexpression of these subunits in
      male, without affecting the responses in female. CONCLUSION: Taken together, our
      findings demonstrate that male SHR presents higher superoxide anion concentration
      under basal condition than does female. An AT-1-dependent overexpression of the
      NAD(P)H-oxidase components may account for the sexual dimorphism in oxidative
      stress, and may play an important role in the noted gender differences on
      incidence of cardiovascular disease.

PMID- 14732199
TI  - Growth hormone-releasing peptide can improve left ventricular dysfunction and
      attenuate dilation in dilated cardiomyopathic hamsters.
AB  - OBJECTIVE: The mammalian heart contains specific growth hormone-releasing peptide
      (GHRP) binding sites whose physiological significance is unknown. We sought to
      compare the effects of GHRP and GH on progressive left ventricular (LV)
      dysfunction in the TO-2 hamster model of dilated cardiomyopathy. METHODS: TO-2
      hamsters (8 weeks old) were injected with GHRP-6 (100 microg/kg day), GH (2 mg/kg
      day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and
      structural changes were evaluated by echocardiography and pathology. RESULTS: The
      increase in body weight of GH-treated TO-2 hamsters was greater than that of
      animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF
      1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS)
      decreased from 42.0+/-2.6% to 25.4+/-1.8% and the LV end-diastolic dimension
      (LVDd) increased from 4.0+/-0.1 to 5.0+/-0.1 mm in untreated TO-2 hamsters
      between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6
      (33.4+/-2.0%) or GH (32.0+/-2.1%). The LVDd was significantly smaller in animals
      treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte
      area and the amount of atrial natriuretic peptide mRNA in the LV were increased
      by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day))
      exerted minimal cardiac and systematic growth effects without improving LV
      function. CONCLUSION: GHRP can ameliorate the development of progressive LV
      dysfunction independently of the GH-IGF-1 axis, suggesting a potential new
      approach to the heart failure.

PMID- 14732200
TI  - Effects of shock strengths on ventricular defibrillation failure.
AB  - BACKGROUND: The mechanism of defibrillation is controversial. Reentry appearing
      immediately after the shock has been shown to be responsible for defibrillation
      failure in some studies while other studies have demonstrated that a rapid train
      of focal activations with the first focus appearing >50 ms after the shock is
      responsible for failed defibrillation. We tested the hypothesis that both
      patterns can occur, but at different shock strengths. METHODS AND RESULTS:
      Biphasic 6/4 ms shocks of 100-900 V in 100-V increments were given after 10 s of
      ventricular fibrillation from electrodes in right ventricular apex and right
      atrium in five isolated pig hearts. Transmembrane activity was optically mapped
      from the anterior and posterior epicardium using two CCD cameras. The
      defibrillation threshold (DFT) was 786+/-199 V. The interval from the shock to
      the earliest post-shock activation was zero for shocks <400 V but increased with
      increasing shock voltage to 62+/-6 ms at 800 V. The number of post-shock phase
      singularities, which is related to reentry incidence, decreased continuously from
      pre-shock values for 100-V shocks to zero as the shock strength increased to 600
      V. Focal activations were observed after shocks >600 V with no epicardial reentry
      present. CONCLUSION: Reentry is responsible for defibrillation failure for low
      strength shocks. As the shock strength approaches the DFT, a focal epicardial
      activation pattern becomes responsible for failed defibrillation. Thus, the
      mechanism of defibrillation failure depends on shock strength, with focal
      activation as the mechanism for the clinically important near-DFT strength
      shocks.

PMID- 14732201
TI  - Atrioventricular nodal fast pathway modification: mechanism for lack of
      ventricular rate slowing in atrial fibrillation.
AB  - OBJECTIVES: Atrioventricular node (AVN) modification is one of the alternatives
      for ventricular rate control in patients with drug refractory atrial fibrillation
      (AF). However, the underlying mechanisms, and in particular the role of the dual
      pathway electrophysiology is not clear. By using a novel index, His electrogram
      (HE) alternans, we have previously demonstrated in rabbits that both the slow
      (SP) and the fast pathways (FP) are involved in AVN conduction during AF. This
      electrophysiological-morphological study was designed to address the role of
      selective FP ablation on AVN conduction during AF. METHODS AND RESULTS: In 12
      rabbit AVN preparations dual pathway conduction was confirmed by HE alternans
      during A1A2 pacing protocol, as well as during AF. On average 48% of the
      conducted beats during AF utilized the FP. Selective FP ablation (n=12) guided by
      HE alternans resulted in only-SP conduction, with longer AVN conduction time at
      basic beats, but without change of AVN effective refractory period (ERP).
      Interestingly, despite elimination of all FP-conducted beats during AF, the
      selective FP ablation allowed previously concealed SP beats to be conducted,
      resulting in little net effect on the ventricular rate (average His-His interval
      199+/-10 ms before versus 201+/-13 ms after FP ablation, p>0.05). Morphological
      evidence indicated that FP ablation created lesions within the transitional cells
      of the superior approaches at the junction between the central fibrous body and
      the AVN. However, extension of FP ablation lesion into the compact AVN domain
      resulted in non-selective AVN modification and slowing of ventricular rate during
      AF. CONCLUSIONS: Despite its longer ERP, FP is responsible for a substantial
      number of ventricular beats during AF. However, selective FP ablation has a minor
      effect on ventricular rate. The most likely mechanism for this phenomenon is that
      FP ablation allows previously concealed SP beats to be conducted. On the other
      hand, ventricular rate slowdown could be achieved if FP ablations caused
      collateral damage in the compact node. This study highlights the usefulness of HE
      alternans as a novel tool to monitor dual pathway conduction during AF and to
      guide AVN modification.

PMID- 14732202
TI  - Cloning and initial characterization of the human cardiac sodium channel (SCN5A)
      promoter.
AB  - OBJECTIVE: Despite the primacy of the sodium current in cardiac electrophysiology
      and evidence that decreased sodium current is arrhythmogenic in humans, little is
      known about transcriptional regulation of the underlying gene, SCN5A. METHODS: We
      have cloned a 2.7 kb segment of 5'-flanking region of SCN5A and identified
      multiple transcription initiation sites by primer extension and RNase protection.
      Transient transfection assays in neonatal mouse myocytes and in Chinese Hamster
      Ovary (CHO) cells were employed to identify promoter activities. PCR-single
      stranded conformational polymorphism (SSCP) analysis was used to screen DNA
      variants in the promoter region. RESULTS: The fragment includes >2 kb of upstream
      sequence, the 173-bp non-coding exon 1, and a portion of the 16-kb intron 1; the
      region is highly GC-rich and TATA-less. Transient transfection assays in neonatal
      mouse myocytes and in CHO cells identified (1) a core promoter in the -261/+140
      segment, (2) regions conferring approximately 3-fold decreases from core promoter
      activity in the 5' upstream region (-261/-454 and -1020/-2109), and approximately
      3-fold increases in intron 1 (+255/+410 and+539/+613), and (3) a very strong
      negative regulatory region between +613 and +754 in intron 1. A core promoter
      polymorphism, present in 6/142 (4%) of normal alleles screened, increased
      reporter activity approximately 50% in myocytes but not in CHO cells. CONCLUSION:
      The SCN5A promoter includes multiple positive and negative cis-acting elements
      extending into intron 1. A common polymorphism in this region modulates channel
      expression in vitro.

PMID- 14732203
TI  - Gender determines the acute actions of genistein on intracellular calcium
      regulation in the guinea-pig heart.
AB  - OBJECTIVES: The soy-isoflavone, genistein, appears to be cardioprotective partly
      through direct actions on the heart, although the relative benefits between men
      and women are not fully known. The purpose of the present study was to determine
      whether gender influences the acute electrophysiological actions of genistein at
      the level of isolated cardiac myocytes and to elucidate the mechanisms involved.
      METHODS: Left ventricular myocytes, isolated from weight-matched male and female
      guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion
      chamber (37 degrees C). The effects of acute application of genistein on cell
      shortening and the Ca(2+) transients were measured. Electrophysiological
      recordings were performed using single electrode voltage-clamp. RESULTS:
      Genistein increased cell contraction and the Ca(2+) transients in a concentration
      dependent manner in myocytes from male guinea-pigs [by 54+/-11% and 22+/-4%,
      respectively (mean+/-S.E.M., p<0.001, n=18) at 40 microM], while having no
      significant corresponding effect in those from females. In contrast, genistein
      increased both parameters in myocytes obtained from male and female rats. The
      changes in guinea-pigs occurred despite inhibition of the L-type Ca(2+) current
      in both sexes (n>23, p<0.001). In order to explain these observations, we
      measured sarcoplasmic reticulum (SR) Ca(2+) contents by integrating the
      Na(+)/Ca(2+) exchanger currents (I(NCX)) following rapid caffeine application.
      Genistein increased I(NCX) integrals by 27% in males (n=12, p<0.01) and 20% in
      females (n=14, p<0.01). The increased SR Ca(2+) load in males, but not females,
      could be related to an impaired ability of the Na(+)/Ca(2+) exchanger to extrude
      Ca(2+). CONCLUSIONS: We have demonstrated novel, gender-related differences in
      the acute cardiac actions of genistein, which can be attributed to actions at
      distinct points of the intracellular Ca(2+) cycle. Our results suggest that
      genistein may afford greater cardioprotection in females than in males.

PMID- 14732204
TI  - Quantification of the rat left ventricle force and Ca2+ -frequency relationships:
      similarities to dog and human.
AB  - OBJECTIVE: To measure and quantify the force-frequency (FFR) and Ca(2+)-frequency
      (CaFR) relationships in isolated rat left ventricular (LV) muscle at
      physiological heart rates and compare the obtained FFR to that measured in larger
      mammalian muscle from dog and human using the same experimental protocol.
      METHODS: Rat papillary muscle was isolated from the LV of adult male Sprague
      Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded
      with the Ca(2+) indicator Fura-2, allowed to recover from isolation trauma and
      then subjected to direct electrical stimulation while measuring force production
      and intracellular Ca(2+) transients. RESULTS: We obtained a positive FFR between
      1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial
      muscle strips from dogs and humans with normal LV function. The FFR reflects the
      cytosolic Ca(2+) transients in amplitude. Isoproterenol yielded an enhancement in
      force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of
      FFR amplitude without changing frequency-dependent shape. CONCLUSION: We describe
      an experimental protocol that consistently yields positive FFRs in rat, dog and
      human LV muscle at stimulation rates between 1 and 4 Hz, without significant
      qualitative differences. We attribute previously observed negative FFR in rat
      muscle to an increase in SERCA activity early after excision and preparation of
      the muscle strips.

PMID- 14732205
TI  - Decreased protein and phosphorylation level of the protein phosphatase inhibitor
      1 in failing human hearts.
AB  - OBJECTIVE: The protein phosphatase inhibitor-1 (I-1) is a highly specific and
      potent inhibitor of type 1 phosphatases (PP1) that is active only in its protein
      kinase A (PKA)-phosphorylated form. I-1 ablation decreases, I-1 overexpression
      sensitizes beta-adrenergic signaling in the heart. It is controversial whether I
      1 expression is altered in human heart failure (HF), likely because its detection
      in heart is difficult due to its low abundance. METHODS AND RESULTS: I-1 was >500
      fold enriched from left ventricular myocardium (LVM) from patients with terminal
      HF (n=16) and non-failing controls (NF, n=5) and quantified with an affinity
      purified I-1 and a I-1 phosphospecific antiserum. In non-failing I-1 protein
      levels amounted to 126 fmol/mg protein. In failing hearts, I-1 protein levels
      were reduced by 58% and I-1 phosphorylation by 77% (P<0.001 vs. NF). I-1
      phosphorylation correlated well with serine-16 phosphorylation of phospholamban
      (PLB) in the same hearts (P<0.001). In contrast, PLB, troponin I (TnI) and PP1
      protein and TnI phosphorylation levels did not differ between HF and NF.
      CONCLUSIONS: The results suggest that the reduction in I-1 protein and
      phosphorylation in failing human hearts leads to increased phosphatase activity
      which in turn may result in reduced phosphorylation of cardiac proteins such as
      PLB.

PMID- 14732206
TI  - Altered oscillatory work by ventricular myofilaments from a rabbit coronary
      artery ligation model of heart failure.
AB  - OBJECTIVES: Understanding the changed ability of cardiac myofilaments to produce
      pump work requires knowledge of kinetics of crossbridge function as well as more
      widely studied parameters such as Ca-sensitivity and isometric force development.
      We tested the hypothesis that altered crossbridge kinetics contribute to reduced
      myofilament work in early-stage heart failure (left ventricular dysfunction,
      LVD). METHODS: The sinusoidal oscillation technique can yield insights into
      crossbridge function. Dynamic stiffness, oscillatory work and power were assessed
      in chemically skinned, Ca-activated trabeculae from rabbit ventricles in early
      stage failure, 8 weeks after infarction induced by coronary artery ligation
      (LIG). Results were compared with sham-operated controls (SH). LVD was assessed
      by echocardiography. RESULTS: Ca-activated force and myofilament Ca-sensitivity
      were not significantly altered at this early stage of LVD. In maximally Ca
      activated preparations, the frequency of minimal dynamic stiffness (f(min)) was
      23% lower in LIG. f(min) increases by >80% between pCa 5.8 and 4 in SH but not in
      LIG. Maximal phase lead and lag angles (between length and tension) were lower in
      LIG at frequencies near f(min), lowering oscillatory work and power. The
      Lissajous figures (oscillatory work loops) of imposed length vs. tension are
      often asymmetric near f(min). The degree of asymmetry was greater in LIG.
      CONCLUSIONS: Reduced capacity for mechanical power, consistent with depressed
      haemodynamic performance in LVD hearts, is only partially attributable to
      crossbridge slowing; changes in the phase relationship will also contribute.
      These changes are not readily attributable to known alterations in contractile
      protein isoforms. Some deductions are drawn about which steps in the crossbridge
      cycle are modified in this model of LVD. Altered cardiac myocyte Ca-transients,
      reported to be associated with LVD, will be translated into pump work by a
      contractile machinery that is functionally altered, even though isometric force
      and myofilament Ca-sensitivity might remain near-normal at this stage.

PMID- 14732207
TI  - Norepinephrine-induced acute heart failure in transgenic mice overexpressing
      erythropoietin.
AB  - OBJECTIVE: Overexpression of erythropoietin (Epo) in mice (Epo-tg6) leads to an
      increase in hematocrit and blood volume, and strongly reduces endurance upon
      exercise. It was the aim of this study to characterize the mechanisms underlying
      the reduced cardiac performance. METHODS: Left (LV) and right (RV) ventricular
      function was measured with and without norepinephrine (NE) stimulation in 12
      anaesthetized Epo-tg6 and in 13 wild-type (WT) control mice. RESULTS: There were
      no differences in heart function under baseline resting conditions. Stimulation
      with NE (10 microl bolus injections of 1-100 ng per mouse) in WT mice led to a
      dose-dependent increase in heart rate (HR), LV developed pressure (LVDP) and rate
      of rise in LV pressure (LV dP/dt(max)), while LV end-diastolic pressure (LVEDP)
      was unchanged. Except for HR, these parameters increased to a lesser extent in
      EPO-tg6 mice. Strikingly, LVEDP strongly increased in Epo-tg6 mice after NE (up
      to >20 mmHg). Eleven out of 13 Epo-tg6, but none of the WT mice died or required
      resuscitation after high-doses of NE. In these cases severe diastolic dysfunction
      became overt since the relative myocardial relaxation time was significantly
      prolonged and the duration of diastole was shortened. Moreover, the ECG showed a
      marked ST segment depression as well as deep negative T-waves. The NE-induced
      reduction in myocardial adenosin-triphosphate (ATP) content was more pronounced
      in Epo-tg6 mice after 10 min of continuous NE infusion (50 ng/min per mouse).
      CONCLUSION: NE-induced stress in Epo-tg6 mice led to acute heart failure
      associated with diastolic dysfunction and myocardial ischemia.

PMID- 14732208
TI  - Preconditioning delays Ca2+-induced mitochondrial permeability transition.
AB  - OBJECTIVE: We investigated whether ischemic preconditioning (PC) may modify
      mitochondrial permeability transition (MPT) pore opening. METHODS: In protocol 1,
      New Zealand White rabbits underwent either no intervention (sham group) or 10 min
      of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control)
      by one episode of 5 min of ischemia and 5 min of reperfusion. Rabbits were
      pretreated by either saline or the MPT pore inhibitor cyclosporin A (CsA), or its
      non-immunosuppressive derivative Cs29 (10 mg/kg, IV bolus). Hearts were harvested
      and mitochondria isolated for further assessment of Ca(2+)-induced MPT using a
      Ca(2+)-sensitive micro-electrode. In protocol 2, C and PC hearts underwent 30 min
      of ischemia and 4 h of reperfusion. They were pretreated either by saline, CsA or
      Cs29, as in protocol 1. Infarct size was assessed by triphenyltetrazolium, and
      apoptosis by TUNEL staining. RESULTS: In protocol 1, the Ca(2+) overload required
      to induce MPT pore opening was significantly higher in PC than in C hearts. CsA
      and Cs29 significantly increased the Ca(2+) overload required for MPT pore
      opening. In protocol 2, mean infarct size averaged 25% of the risk region in
      CsA/Cs29 treated hearts versus 15% in PC and 55% in controls (P<0.05 vs. C, P=ns
      vs. PC). Cardiomyocyte apoptosis was significantly reduced by PC and cyclosporin
      treatment with a mean apoptotic index of less than 2% in either group versus more
      than 11% in controls. CONCLUSION: This suggests that delayed opening of MPT pore
      may play a major role in ischemic PC.

PMID- 14732209
TI  - Inhibition of p38 MAPK activity fails to attenuate contractile dysfunction in a
      mouse model of low-flow ischemia.
AB  - OBJECTIVE: The basal activity of p38 MAPK has recently been shown to impair
      myocardial contractility. This kinase is activated by ischemia and short-term
      hibernation. We hypothesized that p38 MAPK activation may contribute to the
      contractile deficit that characterizes low-flow ischemia. METHODS: In Langendorff
      perfused isolated C57BL/6 mouse hearts, perfusion pressure was reduced from 85 to
      15 or 30 mm Hg for 120 min to induce ischemic left ventricular dysfunction. The
      effect of the p38 MAPK inhibitor SB203580 (1 microM/l) on contractile function
      and p38 MAPK activation was assessed. RESULTS: Reduction in perfusion pressure to
      15 or 30 mm Hg was accompanied by stable reductions in coronary flow (83+/-2% and
      66+/-2%, respectively) and developed pressure (84+/-2% and 61+/-3%), with minimal
      infarction (15.6+/-0.69% and 10.6+/-0.98% of LV myocardium, respectively), but
      marked activation of p38 MAPK (reflected in pHSP27 1092+/-326% basal and 996+/
      301% basal, respectively). The p38 MAPK inhibitor SB203580, present during the
      last 60 min of reduced pressure perfusion, prevented p38 MAPK activation (pHSP27
      281+/-92% basal, p=0.01 and 186+/-72% basal, p=0.01) but, despite the presence of
      a contractile reserve, had no effect on developed pressure. Similarly, early
      treatment with SB203580 started 5 min after the onset of reduced flow also failed
      to attenuate contractile dysfunction. CONCLUSION: The p38 MAPK activation that
      accompanies short-term hibernation does not appear to contribute to the
      contractile deficit.

PMID- 14732210
TI  - Conduction performance of collateral vessels induced by vascular endothelial
      growth factor or basic fibroblast growth factor.
AB  - OBJECTIVE: In the present study, we delivered vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind
      limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the
      functional performance of the developed collateral vessels. METHOD: The left
      femoral artery of a male Japanese White rabbit was excised to induce limb
      ischemia, and a section of skin was resected for culture of auto-fibroblasts.
      Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was
      adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and
      the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells)
      was injected via the left internal iliac artery of the same rabbit. Pairs of
      transferred genes into the fibroblasts were as follows: LacZ/LacZ (control
      group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination
      group). Twenty-eight days after cell administration, collateral development and
      its function were evaluated. RESULTS: Calf blood pressure ratio, resting blood
      flow of the left iliac artery and capillary density of ischemic muscle showed
      similar degrees of angiogenic effects in the VEGF and FGF groups, which were
      significantly greater than those in the control group. On the contrary,
      angiographic score, collateral conductance and smooth muscle cell (SMC)-positive
      vessel density in the FGF group were significantly greater than those in the VEGF
      group. In the combination group, collateral conductance showed synergistic
      effects, and in vivo blood flow and smooth muscle cell-positive vessel density
      revealed additive effects of VEGF and bFGF. CONCLUSION: These findings suggested
      that bFGF-induced collateral development exceeded VEGF-induced collateral
      development in the induction of arteriogenesis, and that combined gene delivery
      of VEGF and bFGF produced additive or synergistic effects of collateral
      development as compared with the effects induced by transfer of each gene alone.

PMID- 14732211
TI  - Norepinephrine induces apoptosis in neonatal rat endothelial cells via down
      regulation of Bcl-2 and activation of beta-adrenergic and caspase-2 pathways.
AB  - OBJECTIVES: Heart failure is associated with increased plasma norepinephrine (NE)
      and endothelial apoptosis. Recent reports have suggested that endothelial
      dysfunction is an important target for future therapies of heart failure.
      However, whether NE can induce endothelial apoptosis and its mechanism remains
      unknown. METHODS: Endothelial cells from neonatal rat heart were treated with
      various concentrations of NE for different durations. Apoptosis was assessed by
      terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and DNA
      fragmentation assays. Caspase activity was measured using specific fluorogenic
      substrates. Proteins of Bcl-2 family and cytochrome c were assayed by Western
      blotting. RESULTS: NE induced endothelial apoptosis in a dose- and time-dependent
      manner. After treatment for 48 h, increasing NE concentration from 5, 10, 50, 100
      to 200 microM resulted in 6+/-3%, 14+/-5%, 43+/-4%, 66+/-5%, and 89+/-6%
      apoptotic cells, respectively. The apoptosis was accompanied by down-regulation
      of Bcl-2 protein synthesis but not by cytosolic cytochrome c translocation.
      Caspase-2, -3, -6 and -9 were activated during apoptosis and caspase-2 inhibitor
      (Z-VDVAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) significantly attenuated the
      apoptosis. Overexpression of Bcl-2 inhibited caspase activity and decreased the
      apoptosis. Moreover, the NE-mediated apoptotic effect was attenuated by beta-
      (beta2>beta>beta1) adrenergic antagonists (ICI-118,551>propranolol>atenolol) but
      was not affected by alpha1- or alpha2-adrenergic antagonists (prazosin or
      yohimbine). CONCLUSION: Our study is the first report documenting that NE induces
      apoptosis in neonatal rat endothelial cells mainly through down-regulation of Bcl
      2 protein and activation of the beta-adrenergic (beta2>beta1) and caspase-2
      pathways. beta-Adrenergic antagonists and caspases inhibitors may be useful in
      the prevention and management of NE-mediated endothelial apoptosis during heart
      failure.

PMID- 14732212
TI  - YC-1 prevents sodium nitroprusside-mediated apoptosis in vascular smooth muscle
      cells.
AB  - OBJECTIVE: Nitric oxide signaling pathways are of central importance in both the
      maintenance of vascular homeostasis and the progression of vascular disease.
      Since smooth muscle cell apoptosis is associated with numerous vascular
      disorders, the authors investigated whether YC-1, a soluble guanylyl cyclase
      (sGC) activator, regulates apoptosis in vascular smooth muscle cells (VSMC).
      METHODS AND RESULTS: Sodium nitroprusside (SNP) (1 mM) induced cGMP (guanosine
      3':5'-cyclic monophosphate)-independent apoptosis in rat vascular smooth muscle
      cells using MTT assay and TUNEL-reaction techniques. Furthermore, sodium
      nitroprusside induced apoptosis via Bcl-2 down-regulation, cytochrome c release
      reaction, and caspase-3 activation by Western blotting analysis and enzymatic
      assay methods. YC-1 abolished these apoptotic signaling cascades and prevented
      apoptosis through a cGMP-involved pathway, and phosphatidylinositol (PI) 3-kinase
      behaved a downstream event in this pathway. CONCLUSIONS: These results suggest
      that YC-1 inhibits sodium nitroprusside-induced vascular smooth muscle cells
      apoptosis via a cGMP- and phosphatidylinositol 3-kinase-involved inhibition on
      Bcl-2 down-regulation/cytochrome c release/caspase-3 activation cascades. The
      ability of YC-1 to prevent smooth muscle cell apoptosis may play an important
      role in blocking lesion formation at sites of vascular injury.

PMID- 14732213
TI  - Angiotensin II induces endothelin-1 gene expression via extracellular signal
      regulated kinase pathway in rat aortic smooth muscle cells.
AB  - OBJECTIVE: Angiotensin II (Ang II) increases vascular endothelin-1 (ET-1) tissue
      levels, which in turn mediate a major part of Ang II-stimulated vascular growth
      and hypertension in vivo. Ang II also stimulates reactive oxygen species (ROS)
      generation in vascular smooth muscle cells (SMCs). However, whether ROS are
      involved in Ang II-induced ET-1 gene expression and the related intracellular
      mechanisms in vascular SMCs remains to be determined. METHODS: Cultured rat
      aortic SMCs were stimulated with Ang II, [3H]thymidine incorporation and the ET-1
      gene expression was examined. Antioxidants pretreatment on Ang II-induced
      extracellular signal-regulated kinase (ERK) phosphorylation were performed to
      elucidate the redox-sensitive pathway in proliferation and ET-1 gene expression.
      RESULTS: Ang II-increased DNA synthesis was inhibited by AT(1) receptor
      antagonist (olmesartan) and ET(A) receptor antagonist (BQ485). ET-1 gene was
      induced with Ang II as revealed by Northern blotting and promoter activity assay.
      Ang II-increased intracellular ROS levels were inhibited by olmesartan and
      antioxidants. Antioxidants suppressed Ang II-induced ET-1 gene expression and ERK
      phosphorylation. An ERK inhibitor U0126 fully inhibited Ang II-induced ET-1
      expression. Co-transfection of dominant negative mutant of Ras, Raf and MEK1
      attenuated the Ang II-increased ET-1 promoter activity, suggesting that the Ras
      Raf-ERK pathway is required for Ang II-induced ET-1 gene. Truncation and
      mutational analysis of the ET-1 gene promoter showed that activator protein-1 (AP
      1) binding site was an important cis-element in Ang II-induced ET-1 gene
      expression. Moreover, Ang II- or H(2)O(2)-induced AP-1 reporter activities were
      also inhibited by antioxidants. CONCLUSIONS: Our data suggest that ROS are
      involved in Ang II-induced proliferation and the redox-sensitive ERK pathway
      plays a role in ET-1 gene expression in rat aortic SMCs.

PMID- 14732214
TI  - Fish oil increases antioxidant enzyme activities in macrophages and reduces
      atherosclerotic lesions in apoE-knockout mice.
AB  - OBJECTIVES: The molecular and cellular mechanisms that fish oil (FO) exerts its
      physiological function are complicated. The present study brings evidence on the
      in vivo effect of FO on the development of atherosclerosis in apolipoprotein E
      knockout (apoE(-/-)) mice. We also test the hypothesis that the modulation of the
      cellular oxidative stress and antioxidant status contributes to the anti
      atherosclerotic effect of FO. METHODS AND RESULTS: ApoE(-/-) mice were fed a diet
      rich either in FO or corn oil (CO) for 10 weeks. Both FO and CO had a plasma
      triacylglycerol-raising effect in apoE(-/-) mice, whereas aortic atherosclerotic
      lesions were significantly reduced in the mice that had consumed a high FO diet
      compared to those fed a high CO diet. The levels of hepatic superoxide dismutase
      (SOD) and catalase (CAT) activities were remarkably higher in the mice fed the FO
      diet than in mice fed the CO diet and the control diet. We then investigated the
      effects of FO and CO on the production of superoxide anion (O2*-)) and reactive
      oxygen species (ROS) in cultured J774 macrophages. Antioxidant status was
      assessed by the determination of antioxidant enzyme activities. Both FO and CO
      induced high levels of O2*-) and total ROS at a short time in macrophages.
      However, only the FO group restored the induction of O2*-) and ROS to near basal
      levels after oil treatment for 24 h. Throughout the time course experiments,
      antioxidant enzyme activities in the FO group mostly displayed a greater increase
      than in the corresponding CO group after the same time period of oil treatment.
      CONCLUSIONS: In the present study, FO reduced the formation of atherosclerotic
      lesions in the aortic arteries of apoE(-/-) mice not through any lipid-lowering
      effect. The protective role of FO in the development of atherosclerosis may
      result from its antioxidative defense mechanism through the induction of
      antioxidant enzyme activities.

PMID- 14732215
TI  - Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis
      in rabbit atheromatous arteries.
AB  - OBJECTIVE: Prostacyclin synthase (PGIS) gene transfer have been shown to
      accelerate re-endothelialization and prevent neointimal formation in balloon
      injured arteries. The aim of this study is to evaluate how overexpression of
      endogenous prostacyclin exerts those beneficial effects in atheromatous arteries.
      METHODS: New Zealand White Rabbits fed a 0.5% cholesterol diet underwent balloon
      injury and Palmaz-Schatz stent implantation in the iliac arteries followed PGIS
      gene (pCMV-PGIS, 200 microg) delivery by the lipotransfection method via Dispatch
      catheter (n=6 each). RESULTS: One week after transfection, arterial segments of
      pCMV-PGIS produced higher levels of 6-keto-PGF1alpha than those of control, pCMV
      LacZ (p<0.05). The levels of vascular endothelial growth factor (VEGF) expression
      was greater in the vessels of pCMV-PGIS than in those of pCMV-LacZ demonstrated
      by immunohistochemical analysis and quantitation of Western blotting (1.8-fold,
      p<0.05). At 2 weeks, in-stent endothelialization was significantly greater in the
      vessels of pCMV-PGIS than in those of pCMV-LacZ (p<0.01). The percentage of BrdU
      positive nuclei in the injured arterial segments was lower in vessels of pCMV
      PGIS than pCMV-LacZ (p<0.01). At 4 weeks, PGIS gene transfer reduced the
      neointimal area by 38% (p<0.05) and widened the lumen area by 71% (p<0.01).
      CONCLUSION: PGIS gene transfer accelerated re-endothelialization, and attenuated
      neointimal formation after stent implantation in atheromatous rabbit arteries, at
      least in part, via increased production of VEGF protein.

PMID- 14732216
TI  - Increased collagen turnover is only partly associated with collagen fiber
      deposition in the arterial response to injury.
AB  - OBJECTIVE: In the arterial response to injury, collagen breakdown has been
      studied extensively, but little is known on collagen synthesis and fiber
      formation. Here, we studied in vivo collagen synthesis and collagen fiber content
      in relation to collagen breakdown following arterial balloon injury. METHODS AND
      RESULTS: Twenty-five New Zealand White rabbits were balloon dilated in femoral
      and iliac arteries and terminated at 2, 7, 14 and 28 days. From day 7, both
      constrictive arterial remodeling and intimal hyperplasia were observed. Collagen
      degradation, synthesis and fiber content were studied using zymography,
      quantitative Polymerase Chain Reaction, Western blotting and picrosirius red
      staining. Collagen synthesis, reflected by procollagen I and heat shock protein
      47 (Hsp47) expression, increased at day 2 with a maximum at day 14 and was
      accompanied by increased collagen breakdown as reflected by matrix
      metalloproteinase-1 and -2 levels. Collagen content in media and adventitia only
      increased between days 2 and 7 after balloon injury. CONCLUSIONS: In the first
      week after arterial injury, increased collagen content is associated with
      increased collagen synthesis and degradation. However, after 1 week, collagen
      turnover remains high in contrast to increased collagen fiber content. This
      suggests that after 1 week, collagen turnover is used for other processes like
      cell migration and arterial remodeling.

PMID- 14732217
TI  - Activity of the Akt/GSK-3beta pathway in the failing human heart before and after
      left ventricular assist device support.

PMID- 14732219
TI  - Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen
      species in DNA-oxidation.
AB  - We investigated the biological effects of the active oxygen produced by P450s.
      First, we identified which isoforms of P450 efficiently produced active oxygen
      using electron spin resonance. Eight forms of P450 purified from rat liver were
      used. Of these, CYP1A2, 2B1, 2C11 and 3A2 produced hydroxyl radicals efficiently.
      Phenobarbital (PB) which is a typical inducer of CYP2B1 and 3A2 induced
      production of hydroxyl radicals by rat liver and ketoconazole, an inhibitor of
      P450, inhibited production of hydroxyl radicals in vitro. PB is a tumor promoter
      as well as the P450-inducer. We investigated oxidation of the genomic DNA by the
      hydroxyl radicals produced by PB-inducible P450 in vitro and in vivo. 8-hydroxy
      2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation in vivo was assayed by
      HPLC. PB strongly induced the production of 8-OHdG in the rat liver. While
      ketoconazole inhibited the production of 8-OHdG in vivo. These results suggest
      that active oxygen produced by P450 oxidized genomic DNA and induction of P450
      increased oxidative stress that may contribute to tumor initiation and promotion.

PMID- 14732220
TI  - The anti-inflammatory potential of berberine in vitro and in vivo.
AB  - Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects,
      including anti-inflammation, yet the exact mechanism is unknown. Because
      cyclooxygenase-2 (COX-2) plays a key role in prostaglandins (PGs) synthesis,
      which is elevated in inflammation, we examined whether the anti-inflammatory
      mechanism of berberine is mediated through COX-2 regulation. In oral cancer cell
      line OC2 and KB cells, a 12 h berberine treatment (1, 10, and 100 microM) reduced
      prostaglandin E2 (PGE2) production dose-dependently with or without 12-O
      tetradecanoylphorbol-13-acetate (TPA, 10 nM) induction. This berberine induced
      effect occurred rapidly (3 h) as a result of reduced COX-2 protein, but not
      enzyme activity. The electrophoretic mobility shift assay revealed that activator
      protein 1 (AP-1) binding was decreased in oral cancer cells treated with
      berberine for 2 h. Further analysis showed that berberine inhibited AP-1 binding
      directly. These anti-inflammatory effects paralleled to the in vivo results where
      berberine pretreatment of Wistar rat inhibited the production of exudates and
      PGE2 in carrageenan induced air pouch.

PMID- 14732221
TI  - Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo
      deoxyguanosine formation in human mammary epithelial cells.
AB  - The effect of ethanol and acetaldehyde treatment on the removal of benzo[a]pyrene
      diol-epoxide (BPDE)-DNA adducts in the immortalized, human mammary epithelial
      cell line MCF-10F was examined. Treatment of cells with 15 mM and 25 mM ethanol
      resulted in significantly more BPDE-DNA adducts/unit DNA remaining at multiple
      time points, compared to controls. The half-life of BPDE-DNA adducts in cells
      exposed to both 15 and 25 mM ethanol were 11.9 and 12.3 h, respectively, compared
      to a half-life of 9.8 h for the control cells. In contrast, for cells exposed to
      acetaldehyde at doses of 2.5 and 5.0 microM no significant trend in BPDE-DNA
      adduct persistence occurred, compared to controls. The inhibition of adduct
      removal for cells treated with ethanol was not associated with any changes in
      cell viability due to ethanol exposure. However, BP-treated cells exposed to 25
      mM ethanol exhibited a significant 2-fold increase in 8-oxo-deoxyguanosine (8-oxo
      deG) adducts compared to BP-treated cells alone. No significant increase in 8-oxo
      deG was observed for cells treated with BP and exposed to 5.0 microM
      acetaldehyde. Thus, ethanol exposure of human mammary epithelial cells is
      associated with a decreased capacity to remove BPDE-DNA adducts. This inhibitory
      effect of ethanol on adduct removal in part may be related to ethanol-associated
      oxidative stress.

PMID- 14732222
TI  - TNF-alpha-mediated apoptosis in normal human prostate epithelial cells and tumor
      cell lines.
AB  - In this study we compared the role of TNF-alpha in the regulation of growth and
      apoptosis in normal human prostate epithelial cells (NP) and prostate tumor cell
      lines PC3 and LNCap. The NP and PC3 cells were resistant whereas the LNCap cell
      line was highly sensitive to TNF-alpha induced growth arrest and apoptosis. The
      resistance of NP and PC3 cells was mediated via an NF-kB survival pathway as
      treatment of resistant cells with TNF-alpha was accompanied by phosphorylation of
      I-kBalpha and translocation of NF-kB to the nucleus. TNF-alpha did not induce
      phosphorylation of I-kB in the sensitive LNCap cells. The sensitivity of LNCap
      cells involved a cysteine protease cascade as Z-VAD-CH2 F reversed the
      sensitivity of LNCap cells and induced resistance to TNF-alpha. The differences
      in susceptibilities to TNF-alpha induced apoptosis of NP and certain prostate
      tumor cells offer intriguing possibilities for the treatment of prostate cancer
      without affecting the normal prostate tissue.

PMID- 14732223
TI  - Enhanced chemosensitivity of bladder cancer cells to cisplatin by suppression of
      clusterin in vitro.
AB  - We examined the functional role of clusterin in chemotherapy-induced apoptosis
      and tested whether anti-sense transfection targeted against clusterin enhances
      the chemosensitivity in human bladder cancer cells in vitro. Clusterin mRNA and
      protein expression of 253J cells, a human bladder carcinoma cell line, after
      treatment with cisplatin were measured by RT-PCR and Western blot analysis.
      Clusterin expression and cell growth were compared between 253J cells transfected
      with constructed a clusterin anti-sense plasmid vector (pCR-CLU-AS) and controls.
      Tumor cell viability was measured with MTT assay after cisplatin treatment. DNA
      fragmentation and CPP32 assay were performed. Clusterin expression was increased
      after treatment with cisplatin and highest at 8 h in 253J cells. Clusterin anti
      sense transfectants were highly sensitive to apoptotic cell death induced by
      cisplatin compared with parental 253J cells or control transfectants.
      Collectively, our results showed that expression of clusterin was increased in
      the acute phase of cell death caused by cisplatin and that suppressing the
      expression of clusterin enhanced the susceptibility of apoptosis caused by
      cisplatin in human bladder cancer cells. These results suggest that lowering the
      expression of clusterin might increase the sensitivity of bladder cancer cells to
      chemotherapeutic agents.

PMID- 14732224
TI  - Psammaplin A, a marine natural product, inhibits aminopeptidase N and suppresses
      angiogenesis in vitro.
AB  - Psammaplin A (PsA) is a phenolic natural product isolated from a marine sponge,
      which showed a potent cytotoxicity against several cancer cell lines. In present
      study, PsA was found to inhibit mammalian aminopeptidase N (APN) that plays a key
      role in tumor cell invasion and angiogenesis. PsA inhibited the APN activity with
      an IC50 of 18 microM in a non-competitive manner. Moreover, PsA potently
      inhibited the proliferation of several cancer and endothelial cells.
      Interestingly, the anti-proliferative effect of PsA was dependent on the cellular
      amount of APN expression. Finally, PsA suppressed the invasion and tube formation
      of endothelial cells stimulated by basic fibroblast growth factor. These data
      demonstrate that PsA is a new inhibitor of APN and can be developed as a novel
      anti-angiogenic agent.

PMID- 14732225
TI  - Combined chemotherapeutic and photodynamic treatment on human bladder cells by
      hematoporphyrin-platinum(II) conjugates.
AB  - Four porphyrin-platinum complexes, conceived as a new approach in cancer therapy
      by combining the cytostatic activity of cisplatin or oxaliplatin and the
      photodynamic effect of hematoporphyrin in the same molecule, were studied in
      detail with respect to solubility and stability in cell culture medium as well as
      in terms of cytotoxicity and phototoxicity against J82 bladder cancer cells and
      UROtsa, normal urothelial cells. This study demonstrated that the most active and
      promising compound among the porphyrin-platinum conjugates investigated was the
      water-soluble porphyrin-platinum complex 4 (diammine[7,12-bis[1
      (polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17
      tetramethylporphyrin-2,18-dipropionato]platinum(II)) which exhibited a
      synergistic antiproliferative effect compared to cisplatin and hematoporphyrin
      alone or a combination of the drugs.

PMID- 14732226
TI  - Prognostic significance of microsatellite instability in curatively resected
      adenocarcinoma of the small intestine.
AB  - Adenocarcinoma of the small intestine (ACSI) is a rare condition with few studies
      addressing follow-up and prognosis. Tumors of 35 patients with curative resection
      of an ACSI were retrospectively analyzed by immunohistochemistry: p53, hMLH1,
      hMSH2 and hMSH6 and microsatellite instability (MSI): BAT-26, BAX, TGF-beta RII.
      With a median follow up of 6.1 years, the median cancer-specific survival (CSS)
      was 36.2 months. Patients who were highly instable (MSI-H) (n=10) had a CSS of
      49.6 months in contrast to patients with stable tumors (23.2 months) (P=0.010).
      Additionally, a low tumor stage according to UICC and MSI-H were shown to be
      independent factors (P=0.005 and P<0.001) for an increased survival in
      multivariate analysis. Therefore, it is suggested that analysis of the MSI status
      might prove useful in discerning prognosis within cancers of the same stage.

PMID- 14732227
TI  - C2-ceramide as a cell death inducer in HC11 mouse mammary epithelial cells.
AB  - Ceramide is a lipid mediator in cell proliferation, differentiation, and
      apoptosis in many cell lines. However, the molecular mechanisms for ceramide have
      not been clarified in HC11 mouse mammary epithelial cells. Under phase contrast
      microscope, C2-ceramide-treated cells clearly showed morphological changes, which
      were characteristic features of apoptosis. Treatment with C2-ceramide at 10
      microM specifically resulted in the death of 50% of the cells after 48 h as
      assessed by MTT assay. To further investigate which genes contribute to cell
      death in C2-ceramide-treated cells, we used the reverse transcription-polymerase
      chain reaction to assess mRNA levels for five genes in the Bcl-2 family and five
      genes in the caspases family. The steady-state mRNA levels of Bax, Bad and Bak
      were not significantly changed for 48 h of C2-ceramide treatment. The increases
      of mRNA levels of Bcl-2 and Bcl-w were observed for the first 3 h of C2-ceramide
      treatment and the last 24 h between 24 and 48 h. We also found that in HC11
      cells, C2-ceramide increased mRNA levels of the caspases family from 6 to 24 h.
      These results suggest that in the HC11 cells, C2-ceramide promote cell death by
      mediating the induction of caspases and that HC11 mouse mammary epithelial cells
      paradoxically up-regulate the expression of Bcl-2 and Bcl-w to prevent C2
      ceramide-mediated cell death.

PMID- 14732228
TI  - Glutathione S-transferase P1 has protective effects on cell viability against
      camptothecin.
AB  - Glutathione S-transferase P1 (GSTP1) is one of the important xenobiotic
      metabolizing enzymes. It was reported that GSTP1 was overexpressed in malignant
      tissues, and its expression level was associated with resistance to
      chemotherapeutics. We carried out transfection of GSTP1 sense and antisense
      vectors to examine effects of GSTP1 on cell cycle arrest and apoptosis induced by
      camptothecin in HeLa cells. Transfection of GSTP1 antisense vector induced
      apoptosis. Camptothecin-induced S- or G2/M arrest was intensified by transfection
      of GSTP1 antisense vector, and subsequent apoptosis was attenuated by
      transfection of GSTP1 sense vector. These results suggest that GSTP1 has
      protective effects against camptothecin-induced cytotoxicity.

PMID- 14732229
TI  - Expression and regulation of tumor suppressor gene maspin in human bladder
      cancer.
AB  - Maspin is a member of serine protease inhibitor family with tumor suppressing
      activity for breast and prostate cancers, acting at the level of tumor invasion
      and metastasis. However, there have been no published data regarding the role of
      maspin in human bladder cancer. We evaluated maspin expression in 65 series of
      bladder cancer samples (22 transurethral resection (TUR) and 43 radical
      cystectomy) and studied the regulatory mechanism of maspin gene activation in
      bladder cancer cells. Maspin expression was immunohistochemically detected in
      four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy
      whereas no expression was observed in normal transitional cells located at tumor
      free area in bladder. The maspin expression was significantly correlated with the
      development of muscle invasive bladder cancer (P=0.00008). Using a luciferase
      reporter system, maspin promoter activity was induced in the maspin-positive
      bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore,
      treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and
      histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in
      RT4 cells. Our results indicate that maspin may contribute to bladder cancer
      development and that DNA methylation and histone deacetylation may be important
      for regulating maspin gene activation in bladder cancer cells.

PMID- 14732230
TI  - The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates
      with the reduced p16INK4a/p14ARF proteins.
AB  - To clarify the roles of Bmi-1 in colorectal carcinoma, we examined the expression
      of Bmi-1 in 41 samples out of 46 colorectal carcinomas by reverse transcription
      PCR, whereas all 46 were analyzed by immunostaining. In addition, we analyzed the
      expression patterns of Bmi-1 in association with p16INK4a and p14ARF (in mouse
      p19ARF) in a series of colorectal carcinomas. The level of Bmi-1 mRNA in the
      carcinoma tissues was significantly higher than those of the adjacent non
      neoplastic colonic mucosal tissues. Immunohistochemistry for Bmi-1 showed
      moderate or strong expression levels in 65% (30/46) of colorectal carcinomas.
      Colorectal carcinomas with moderate or strong Bmi-1 expression were more likely
      to have low levels of the INK4 locus proteins (p16INK4a/p14ARF) (P<0.07). These
      results suggested that modulation of Bmi-1 protein might be involved in human
      colorectal carcinogenesis by repressing the INK4a/ARF proteins.

PMID- 14732231
TI  - Differential downregulation of endoplasmic reticulum-residing chaperones calnexin
      and calreticulin in human metastatic melanoma.
AB  - Characterization of the molecular basis of tumor recognition by T cells has shown
      that major histocompatibility complex (MHC) class I molecules play a crucial role
      in presenting antigenic peptide epitopes to cytotoxic T lymphocytes. MHC class Ia
      downregulation has been repeatedly described on melanoma cells and is thought to
      be involved in the failure of the immune system to control tumor progression.
      Proper assembly of MHC class I molecules is dependent on several cofactors, e.g.
      the chaperones calnexin and calreticulin residing in the endoplasmic reticulum.
      Alterations in the expression of these chaperones may have important implications
      for MHC class I assembly, peptide loading, and presentation on the tumor cell
      surface and thus may contribute to the immune escape phenotype of tumor cells. In
      the present study, we compared melanoma lesions representing different stages of
      tumor progression with regard to the expression of calnexin and calreticulin in
      tumor cells by means of immunohistochemistry. Metastatic melanoma lesions
      exhibited significant downregulation of calnexin as compared to primary melanoma
      lesions. In contrast, chaperone calreticulin was expressed in melanoma cells of
      primary as well as of metastatic lesions. Our data suggest that chaperone
      downregulation, particularly calnexin-downregulation, may contribute to the
      metastatic phenotype of melanoma cells in vivo. Consistently, conserved chaperone
      expression in metastatic melanoma lesions may be a useful criterion for selection
      of patients for treatment with T cell-based immunotherapies.

PMID- 14732232
TI  - How can better farming methods reduce malaria?

PMID- 14732233
TI  - Engineering and malaria control: learning from the past 100 years.
AB  - Traditionally, engineering and environment-based interventions have contributed
      to the prevention of malaria in Asia. However, with the introduction of DDT and
      other potent insecticides, chemical control became the dominating strategy. The
      renewed interest in environmental-management-based approaches for the control of
      malaria vectors follows the rapid development of resistance by mosquitoes to the
      widely used insecticides, the increasing cost of developing new chemicals,
      logistical constraints involved in the implementation of residual-spraying
      programs and the environmental concerns linked to the use of persistent organic
      pollutants. To guide future research and operational agendas focusing on
      environmental-control interventions, it is necessary to learn from the successes
      and failures from the time before the introduction of insecticides. The objective
      of this paper is to describe the experiences gained in Asia with early vector
      control interventions focusing on cases from the former Indian Punjab, Malaysia
      and Sri Lanka. The paper deals primarily with the agricultural engineering and
      land and water management vector control interventions implemented in the period
      1900-1950. The selected cases are discussed in the wider context of environment
      based approaches for the control of malaria vectors, including current relevance.
      Clearly, some of the interventions piloted and implemented early in the last
      century still have relevance today but generally in a very site-specific manner
      and in combination with other preventive and curative activities. Some of the
      approaches followed earlier on to support implementation would not be acceptable
      or feasible today, from a social or environmental point of view.

PMID- 14732234
TI  - Opportunities and limiting factors of intensive vegetable farming in malaria
      endemic Cote d'Ivoire.
AB  - Poverty reduction policies guide development strategies. In economies that depend
      heavily on agriculture, in the face of rapid population growth, innovative
      approaches are required to satisfy food needs, increase household welfare and
      alleviate poverty. Irrigated agriculture is an important strategy to enhance crop
      production, but it must be well tailored to specific socio-ecological settings,
      as otherwise, it might increase the burden of water-related parasitic diseases
      and delay economic advance. The purpose of this study is to assess and quantify
      the effect of ill health, particularly malaria, on the performance of farm
      activity, with an emphasis on drip-irrigated vegetable farming in rural Cote
      d'Ivoire. Vegetable yields and revenues were monitored among 12 farmers and
      linked with longitudinal medical and entomological surveys. Over the course of 10
      months, farmers were classified as sick, on average, for 14-15 days, with malaria
      accounting for 8-9 days (58%), confirming that malaria is the most important
      disease in this setting. There was a large heterogeneity among farmers, with
      malaria-related work losses ranging between 0 and 26 days. Work absenteeism
      correlated with overall yields and revenues. During a single cabbage production
      cycle, those farmers who were prescribed sick because of malaria for more than 2
      days (mean: 4.2 days) had 47% lower yields and 53% lower revenues than farmers
      who missed a maximum of 2 days (mean: 0.3 days). This is consequential in an
      intensive cropping system, where substitutes for qualified workers are not
      readily available. We conclude that mitigating the burden of malaria is an
      important step towards reducing the vulnerability of people engaged in intensive
      agricultural production. This calls for targeted interventions to facilitate
      agriculture-based rural development that might spur social and economic
      development and reduce inequities in sub-Saharan Africa.

PMID- 14732235
TI  - Does irrigated urban agriculture influence the transmission of malaria in the
      city of Kumasi, Ghana?
AB  - To verify the possible impact of irrigated urban agriculture on malaria
      transmission in cities, we studied entomological parameters, self-reported
      malaria episodes, and household-level data in the city of Kumasi, Ghana. A
      comparison was made between city locations without irrigated agriculture, city
      locations with irrigated urban vegetable production, and peri-urban (PU)
      locations with rain-fed agriculture. In the rainy as well as dry seasons, larvae
      of Anopheles spp. were identified in the irrigation systems of the urban farms.
      Night catches revealed significantly higher adult anopheline densities in peri
      urban and urban agricultural locations compared to non-agricultural urban
      locations. Polymerase chain reaction (PCR) analysis of Anopheles gambiae sensu
      lato revealed that all specimens processed were A. gambiae sensu stricto. The
      pattern observed in the night catches was consistent with household interviews
      because significantly more episodes of malaria and subsequent days lost due to
      illness were reported in peri-urban and urban agricultural locations than in non
      agricultural urban locations. In Kumasi, urban agriculture is mainly practised in
      inland valleys, which might naturally produce more mosquitoes. Therefore more
      detailed studies, also in other cities with different water sources and
      irrigation systems, and a better spatial distribution of sites with and without
      urban agriculture than in Kumasi are needed.

PMID- 14732236
TI  - The paddy, the vector and the caregiver: lessons from an ecosystem approach to
      irrigation and malaria in Northern Cote d'Ivoire.
AB  - Malaria is one of the most serious public health problems in the world. For the
      last few decades, numerous studies have focused on the potential links between
      environmental transformations (such as the expansion of irrigation) and malaria
      occurrence. Most of these studies have been based on relatively simple models
      outlining the interactions of the host-vector-parasite triad. In this paper, we
      investigate the links between the intensification of irrigated rice cultivation
      and malaria. In an attempt to complement biomedical and entomological approaches
      we propose a model that recognises the influence of human-vector contacts on
      transmission processes, but stresses the importance of taking into consideration
      socio-economic and cultural factors in the management of disease episodes, and
      how these can be affected by transformations of natural resource management
      strategies. Using a case study in Northern Cote d'Ivoire, we investigated the
      complex mechanisms by which agriculture-generated changes in ecosystems and socio
      economic organisation influence disease risks and produce new scenarios in the
      management of disease. Our results show that the socio-economic transformation
      and gender repositioning induced, or facilitated, by the intensification of
      lowland irrigated rice cultivation influence the health care system for malaria
      in the study area. They lead to a reduction of the capacity of women to manage
      malaria episodes among children and influence their vulnerability to the disease.
      We argue that these elements contribute to higher malaria prevalence in villages
      involved in double cropping of rice annually.

PMID- 14732237
TI  - Malaria transmission in relation to rice cultivation in the irrigated Sahel of
      Mali.
AB  - Seven cross-sectional entomological surveys were carried out from September 1995
      to February 1998 in three irrigated rice growing villages and three villages
      without irrigated agriculture in the area surrounding Niono, located 350km north
      east of Bamako, Mali. The transmission pattern differed markedly between the two
      zones. In the irrigated zone, the transmission of malaria was fairly constant
      over the seasons at a low level. In the non-irrigated zone, transmission was
      mostly below detection level during the dry season, whereas it was high toward
      the end of the rainy season. In the irrigated zone, high densities of mosquitoes
      were correlated with low anthropophily, low sporozoite indices and probably low
      survival rates. In the non-irrigated zone, mosquito densities were lower and
      these relationships were less pronounced. Differential use of mosquito nets in
      the two zones may have been an important factor in the observed differences in
      transmission. The presence of cattle may also have played an important role. Two
      mosquito-catching methods (human landing catch and spray catch) were compared.

PMID- 14732238
TI  - Malaria incidence in relation to rice cultivation in the irrigated Sahel of Mali.
AB  - Seven repeated cross-sectional parasitological surveys, collecting a total of
      13,912 blood samples, were carried out from September 1995 to February 1998 in
      three irrigated rice growing villages and three villages without irrigated
      agriculture in the area surrounding Niono, Mali. Parasite prevalence varied
      according to season and agricultural zone, but showed similar patterns for
      villages within the same zone. Overall, malaria prevalence was 47% in the
      villages without irrigated agriculture and 34% in the irrigated rice growing
      villages. In a village in the irrigated zone, and a village in the non-irrigated
      zone, 1067 and 608 children up to the age of 14 years, respectively, were
      followed in a passive malariological study for the period of 13 months. Fevers
      were attributed to malaria using a statistical method, taking into account the
      parasitaemia in afebrile controls from the cross-sectional surveys. The incidence
      of malaria fevers differed markedly between the two zones and over time. In the
      village in the irrigated zone, the incidence of malaria fevers was fairly
      constant over the year at 0.7 per 1000 children per day. In the village without
      irrigated agriculture, incidence was low during the dry season (at 0.6 per 1000
      children per day), whereas it was high during the rainy season (at 3.2 per 1000
      children per day). These results correspond well to the malaria transmission
      observed in a concurrent entomological survey. Rice cultivation in the semi-arid
      sub-Saharan environment altered the transmission pattern from seasonal to
      perennial, but reduced annual incidence more than two-fold.

PMID- 14732239
TI  - A transdisciplinary perspective on the links between malaria and agroecosystems
      in Kenya.
AB  - An ecosystem approach was applied to study the links between malaria and
      agriculture in Mwea Division, Kenya. The study was organized into five phases.
      Phase I had two components including a stakeholder workshop conducted with
      community representatives and other key stakeholders, and the collation of data
      on common diseases from outpatient service records at the local hospital. Phase I
      aimed at an a priori needs-assessment in order to focus the research agenda.
      Workshop participants directly contributed to the selection of two villages with
      rice irrigation and two non-irrigated villages for detailed health studies. In
      Phase II, various Participatory Rural Appraisal (PRA) tools were used to gather
      more detailed qualitative information from the study villages. The qualitative
      results indicated that Mwea residents considered malaria and lack of clean
      drinking water to be their most important health problems, and this was
      corroborated by local hospital records. Phase III consisted of a comprehensive
      household survey developed with inputs from Phases I and II. Phase IV involved a
      comparative evaluation of entomological and parasitological aspects of malaria in
      the villages with and without rice irrigation. The malaria parasitological survey
      found an average Plasmodium falciparum parasite rate of 23.5% among children up
      to 9 years of age. Results of the entomological evaluation showed a 30-300-fold
      increase in the number of the local malaria vector, Anopheles arabiensis, in
      villages with rice irrigation compared to those without irrigation yet malaria
      prevalence was significantly lower in these villages (0-9% versus 17-54%). The
      most likely explanation of this 'paddies paradox' in Mwea appeared to be the
      tendency for A. arabiensis in irrigated villages to feed overwhelmingly on
      cattle. The results suggested that zooprophylaxis was potentially a practical
      option for long-term malaria control in the rice irrigated areas, in spite of the
      large number of A. arabiensis. Phase V consisted of end-of-project workshops for
      the dissemination of research results and participatory decision-making regarding
      follow-up actions. Owing to the utilization of a transdisciplinary and
      participatory approach to research, it was possible to identify opportunities for
      maintaining zooprophylaxis for malaria in Mwea, through the integration of
      agroecosystem practices aimed at sustaining livestock systems within a broader
      strategy for rural development.

PMID- 14732240
TI  - Ammonium sulphate fertiliser increases larval populations of Anopheles arabiensis
      and culicine mosquitoes in rice fields.
AB  - Field experiments were conducted in central Kenya, to study the effect of
      ammonium sulphate fertiliser ((NH(4))(2)SO(4)) on mosquito larval populations in
      rice fields. The experiments used a complete randomised block design having four
      blocks with two experimental ponds per block, and the fertiliser and control
      treatments allocated randomly among the ponds. Student's two-sample unpaired t
      test was used to test for the significance of differences between the relative
      counts of larvae in fertiliser and control treatments. The results showed a
      significant overall increase in the larval populations of An. arabiensis (P<0.01)
      and culicine mosquitoes (P<0.05), after ponds were treated with the fertiliser.
      Significantly more fourth instar larvae of An. arabiensis were collected in
      fertiliser than control plots (P<0.001). An. arabiensis data indicated that the
      first fertiliser application had the most impact, compared to the second and
      third applications. This was evident in a significant peak of combined first and
      second instar An. arabiensis larvae observed 5 days after the first fertiliser
      application (P<0.05). The studies suggest that ammonium sulphate fertiliser
      reduces turbidity of water in rice fields, thereby making them visually more
      attractive for egg-laying by An. arabiensis and culicine mosquitoes.

PMID- 14732241
TI  - Malaria transmission in Southern Madagascar: influence of the environment and
      hydro-agricultural works in sub-arid and humid regions. Part 1. Entomological
      investigations.
AB  - A 4-year entomological study was carried out in Southern Madagascar to identify
      malaria vectors, evaluate the transmission and compare the influence of
      irrigation in the sub-arid and adjacent humid regions. Three villages were
      involved in this entomological survey: Androvasoa (located in the natural sub
      arid ecosystem), Pepiniere (sited at the centre of an irrigated rice scheme in
      the sub-arid region) and Esana (bordered with rice fields in the humid region).
      Mosquitoes were collected inside and outside dwellings when landing on human
      beings, with light traps and with knockdown indoor sprays. Anopheles arabiensis,
      Anopheles merus and Anopheles funestus were found in every village while
      Anopheles gambiae s.s. was only found in the village bordering the rice-fields
      (Pepiniere) and Anopheles mascarensis, a mosquito native to Madagascar, was only
      found in the humid region (Esana). In Pepiniere, the annual entomological
      inoculation rate (EIR) was low (EIR=0.4 infective bites/man/year (IBM)). In the
      irrigated scheme of the sub-arid region, malaria transmission was 150 times
      higher (mean EIR=63 IBM) than in the natural ecosystem and A. funestus was the
      main vector, responsible for 90% of infective bites. In Esana, the level of
      malaria transmission was high (EIR=41 IBM) and 2/3 of the infective bites were
      due to A. mascarensis, despite the presence of A. gambiae s.s. and A. funestus.
      These results are discussed with reference to the impact of irrigation on malaria
      in Africa ("the paddies paradox").

PMID- 14732242
TI  - Malaria and schistosomiasis risks associated with surface and sprinkler
      irrigation systems in Zimbabwe.
AB  - A comparative assessment of the malaria and schistosomiasis risks associated with
      surface and sprinkler irrigation systems in Zimbabwe was carried out. The risk
      assessment of the two diseases was done in accordance with the three standard
      components of health impact assessment, namely (i) community vulnerability, (ii)
      environmental receptivity, and (iii) capability of health services to respond to
      malaria and schistosomiasis. Records of the two diseases were obtained from four
      health centres serving two surface irrigation schemes and two sprinkler
      irrigation schemes. For comparison records were also obtained from health centres
      serving nearby dryland areas. Incidence of schistosomiasis as estimated from
      recorded new cases of the disease was much higher in surface irrigation schemes
      than in sprinkler irrigation schemes. For malaria it was the other way around.
      These findings were confirmed by rapid risk assessments. Malaria risk factors
      were more prominent in sprinkler irrigation schemes, whereas more schistosomiasis
      risk factors were identified in surface irrigation schemes. These observations
      were attributed to poorly maintained infrastructure and inadequate landscape
      levelling, which created mosquito breeding sites within the fields in the case of
      sprinkler schemes, and to poor drainage structures, which created snail-breeding
      sites in the case of surface-irrigation schemes. Importantly, poor maintenance of
      sprinkler scheme infrastructure accounted for more disease promoting features
      than the engineering designs per se. This study demonstrated the value of
      complementing routinely collected health data with rapid assessment procedures
      for appraisal of commonly reported diseases.

PMID- 14732243
TI  - A malaria risk analysis in an irrigated area in Sri Lanka.
AB  - Malaria in Sri Lanka is unstable and epidemic, with large spatial and temporal
      differences in transmission dynamics. The disease is of great public health
      significance and identification of underlying risk factors is important in order
      to use the limited resources in a cost-effective way. The International Water
      Management Institute (IWMI) recently launched a project of GIS-based malaria risk
      mapping in Sri Lanka, to investigate whether this tool could be used for epidemic
      forecasting and for the planning of malaria control activities. This paper
      presents results for the Uda Walawe region in southern Sri Lanka, an irrigated
      agricultural area where malaria cases were mapped at the smallest administrative
      level for each month over a 10-year period. Malaria incidence rates were related
      to land- and water-use patterns, socio-economic features, and data on malaria
      control interventions in a multivariate analysis. Areas of high malaria risk were
      characterized by: (i) higher than average rainfall, (ii) greater forest coverage;
      (iii) slash and burn cultivation as a predominant agricultural activity; (iv)
      presence of many abandoned irrigation reservoirs; and (v) poor socio-economic
      status. Irrigated rice cultivation areas had a lower risk of malaria than non
      irrigated areas. This difference could be due to socio-economic factors related
      to irrigation development and/or transmission dynamics related to vector density
      or species composition. Our findings call for malaria control strategies that are
      readily adapted to different ecological and epidemiological settings. Malaria
      risk maps are a convenient tool for discussing targeted and cost-effective
      interventions with disease control personnel.

PMID- 14732244
TI  - A review of the emergence of Plasmodium falciparum-dominated malaria in irrigated
      areas of the Thar Desert, India.
AB  - Recently, there has been a resurgence of malaria in several parts of India, and
      the Thar Desert in north-western India, is currently suffering from the impact of
      repeated annual epidemics. Nearly all malaria epidemics in the Thar Desert have
      come about with the progression of canal-irrigation work, particularly the
      massive Indira Gandhi Nahar Pariyojana (IGNP). Therefore, the Thar Desert
      provides an excellent model for understanding the underlying factors responsible
      for the exacerbation of malaria, pathways of evolution of the epidemics,
      succession in anopheline fauna, changes in the vector breeding and feeding
      preferences and, most importantly, the possible repercussions of mismanagement of
      irrigation systems. Before the initiation of canalised irrigation only Anopheles
      stephensi, breeding exclusively in household and community-based underground
      water reservoirs, and transmitting malaria at a low level, was prevalent in the
      interior of the Thar Desert. Since the 1980s, extensive irrigation with water
      from three different canal systems has altered the desert physiography, vector
      preponderance, distribution and vectorial capacity, whilst triggering the
      emergence of Plasmodium falciparum-dominated malaria in the virgin levees of the
      Thar Desert. The major objective of bringing the Himalayan waters to the xeric
      environment of the Thar was to transform it into verdure through growing
      irrigation-intensive crops like paddy, groundnut, cotton, mustard, wheat and
      sugarcane, besides providing drinking water to the desert dwellers. The change in
      crop pattern, retention of high surface moisture, and excessive canalisation rife
      with mismanagement of irrigation water have attracted several anophelines,
      including Anopheles culicifacies, which were earlier unknown in the desert. Thus,
      A. culicifacies has penetrated into the interior of the Thar Desert, along with
      irrigation and is now established in vast areas covered by the IGNP project. The
      distribution of P. falciparum-dominated malaria in the Thar Desert is more or
      less synchronous with the spread of IGNP-related irrigated agriculture and of A.
      culicifacies.

PMID- 14732245
TI  - New irrigation methods sustain malaria control in Sichuan Province, China.
AB  - Malaria appears to have been all but eradicated from certain areas of Sichuan
      Province mainly as a consequence of draining a sufficient proportion of rice
      paddy fields. The two main malaria vectors, both members of the Anopheles
      hyrcanus group, breed prolifically in rice paddy fields, which farmers have
      traditionally kept flooded all year round to ensure an adequate water supply.
      Over the last three decades, the irrigation network has been gradually extended,
      thus ensuring water security and increasing the area of arable land that could be
      farmed by intermittent wet/dry irrigation (IWDI). In addition, rice fields that
      had been left flooded but fallow throughout the winter are now under an annual
      cycle of wet crop/dry crop rotation (WDCR) to maximise productivity. Accordingly,
      vector breeding has been greatly reduced. It would appear that vector populations
      have now fallen below the level required to sustain malaria transmission.

PMID- 14732246
TI  - Malaria from the gap: need for cross-sector co-operation in Azerbaijan.
AB  - This study explores the agricultural, environmental, and institutional
      determinants of malaria in Azerbaijan in 1999 and discusses ways to avoid its
      future outbreaks. Regression analysis and geographical maps are used to identify
      important policy variables for designing and implementing malaria control
      strategies. Results show that irrigation water use and soil salinity are
      significantly associated with malaria incidence, warranting further research to
      better understand the exact linkage mechanisms between agriculture and malaria.
      This also points out that there is scope for co-operation of agricultural,
      environmental and health organisations to reduce the spread of malaria.

PMID- 14732247
TI  - Research advances in the use of tetrapyrrolic photosensitizers for photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) is a promising new treatment modality for several
      diseases, most notably cancer. In PDT, light, O2, and a photosensitizing drug are
      combined to produce a selective therapeutic effect. Lately, there has been active
      research on new photosensitizer candidates, because the most commonly used
      porphyrin photosensitizers are far from ideal with respect to PDT. Finding a
      suitable photosensitizer is crucial in improving the efficacy of PDT. Recent
      synthetic activity has created such a great number of potential photosensitizers
      for PDT that it is difficult to decide which ones are suitable for which
      pathological conditions, such as various cancer species. To facilitate the choice
      of photosensitizer, this review presents a thorough survey of the photophysical
      and chemical properties of the developed tetrapyrrolic photosensitizers. Special
      attention is paid to the singlet-oxygen yield (PhiDelta) of each photosensitizer,
      because it is one of the most important photodynamic parameters in PDT. Also, in
      the survey, emphasis is placed on those photosensitizers that can easily be
      prepared by partial syntheses starting from the abundant natural precursors,
      protoheme and the chlorophylls. Such emphasis is justified by economical and
      environmental reasons. Several of the most promising photosensitizer candidates
      are chlorins or bacteriochlorins. Consequently, chlorophyll-related chlorins,
      whose PhiDelta have been determined, are discussed in detail as potential
      photosensitizers for PDT. Finally, PDT is briefly discussed as a treatment
      modality, including its clinical aspects, light sources, targeting of the
      photosensitizer, and opportunities.

PMID- 14732248
TI  - Facile synthesis of chlorophyll analog possessing a disulfide bond and formation
      of self-assembled monolayer on gold surface.
AB  - A chlorophyll analog forming self-assembled monolayers (SAMs) on a gold surface
      was synthesized for the first time. 13(2)-(Demethoxycarbonyl)pheophorbide-a,
      which was converted from naturally occurring chlorophyll-a, was condensed with 2
      hydroxyethyl disulfide to give a chlorin dyad linked by a disulfide bond. The
      chlorin analog was spontaneously immobilized on a gold substrate by soaking in an
      acetone solution of the dyad for 24 h. The resulting gold plate exhibited a
      visible absorption spectrum with about 420- and 675-nm maxima as the Soret and Qy
      peaks, respectively, indicating that chlorin pi-conjugates were modified on the
      gold substrate through Au-S bonding. Both visible absorption and fluorescence
      emission bands of the chlorin chromophores on the gold substrate were red-shifted
      compared with those of the synthesized chlorin dyad in a homogeneous acetone
      solution. The measured absorbance at the Soret maximum suggests that the chlorin
      chromophores on the gold plate were densely packed on a gold surface to form a
      SAM. Cathodic photocurrents were generated from SAMs of the chlorins on a gold
      substrate with irradiation of visible-lights above 400 nm. Photoinduced electron
      transfer from chlorins on the gold substrate to oxygen molecules in an
      electrolyte solution were attributed to the cathodic photocurrent generation.

PMID- 14732249
TI  - 5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on
      the patterns of tumour invasion.
AB  - 5-ALA-induced protoporphyrin IX (PPIX) fluorescence kinetics was quantified by
      fluorescence microscopy in three-dimensional organ co-cultures of human bronchial
      epithelium, which were infiltrated by four different lung tumour cell lines (EPLC
      M31, LCLC-103H, NCI-H125 and NCI-H841). Corresponding fluorescence measurements
      were performed in monolayer cultures of these tumour cell lines and BEAS-2B cells
      as a model for normal bronchial epithelium by flow cytometry. Significant
      differences of fluorescence intensities (FI) between the tumours were detected in
      organ co-cultures as well as in single cell measurements. Relative FI values in
      organ co-cultures (FI(EPLC-32M1)>FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)) did not
      correspond to the measurements in single cells (FI(LCLC-H103)>FI(NCI-H125)>FI(NCI
      H841)>FI(EPLC-32M1)). Histology of organ co-cultures revealed different patterns
      of invasion and tumour cell densities depending on the tumour type. After
      correction of FI in the co-cultures to tumour cell density the correlation
      coefficient for fluorescence values between both models increased considerably.
      Thus, additionally to distinctive features of 5-ALA metabolism, patterns of
      tumour invasion may be a factor determining 5-ALA-induced fluorescence.
      Considering these results, a pronounced heterogeneity of 5-ALA-induced
      fluorescence might be expected in different bronchial tumours in vivo. This could
      interfere with the diagnostic reliability of 5-ALA-induced fluorescence for early
      tumour detection.

PMID- 14732250
TI  - Effects of extremely low frequency magnetic field on the antioxidant defense
      system in mouse brain: a chemiluminescence study.
AB  - Among the putative mechanisms, by which extremely low frequency (ELF) magnetic
      field (MF) may affect biological systems is that of increasing free radical life
      span in organisms. To test this hypothesis, we investigated whether ELF (60 Hz)
      MF can modulate antioxidant system in mouse brain by detecting chemiluminescence
      and measuring superoxide dismutase (SOD) activity in homogenates of the organ.
      Compared to sham exposed control group, lucigenin-initiated chemiluminescence in
      exposed group was not significantly increased. However, lucigenin-amplified t
      butyl hydroperoxide (TBHP)-initiated brain homogenates chemiluminescence, was
      significantly increased in mouse exposed to 60 Hz, MF, 12 G for 3 h compared to
      sham exposed group. We also measured SOD activity, that plays a critical role of
      the antioxidant defensive system in brain. In the group exposed to 60 Hz, MF, 12
      G for 3 h, brain SOD activity was significantly increased. These results suggest
      that 60 Hz, MF could deteriorate antioxidant defensive system by reactive oxygen
      species (ROS), other than superoxide radicals. Further studies are needed to
      identify the kind of ROS generated by the exposure to 60 Hz, MF and elucidate how
      MF can affect biological system in connection with oxidative stress.

PMID- 14732251
TI  - Autofluorescence of oral tissue for optical pathology in oral malignancy.
AB  - Pulsed laser-induced-fluorescence studies of pathologically certified oral
      tissues are carried out at different excitations and time delays. Among the
      several excitations used, 325 nm produced noticeably different spectral profile
      for normal and malignant tissues. Extensive curve analysis was carried out in
      order to understand changes in biochemical composition of tissue based on
      spectral profiles. Curve resolution and principal component analysis (PCA) show
      that the fluorescence intensity changes from normal to malignant tissue samples
      are not completely explained in terms of simple collagen and NAD(P)H intensity
      changes. The spectra require at least five components to be fully accounted for.
      Several discrimination methodologies based on PCA and intensity differences
      between different emission peaks (resultant peaks of curve analysis) were also
      evaluated. The results obtained indicate PCA using Mahalanobis distance and
      spectral residual as discrimination parameters provides best discrimination and
      can be used for matching unknown samples to standard calibration sets. Intensity
      ratio of bound NAD(P)H to collagen seems to be more suitable for discrimination
      between normal and malignant oral tissue, compared to ratio of collagen to total
      intensity of all the other components together.

PMID- 14732252
TI  - Alternative methods to evaluate the protective ability of sunscreen against photo
      genotoxicity.
AB  - Numerous epidemiological investigations show that sunlight is carcinogenic to
      humans and that the use of sunscreen may be effective in decreasing the risk of
      skin cancer. The biological activity of a sunscreen is evaluated by its ability
      to protect human skin from erythema as represented by a Sun Protection Factor
      (SPF). We propose that the sunscreen's protective effect against sunlight-induced
      genotoxicity, including mutation, should also be taken into account. In this
      study we examined the protective ability of sunscreens against natural sunlight
      and UV-induced genotoxicity in Drosophila somatic cells. We prepared three kinds
      of sunscreen samples, each with an SPF value of 20, 40 or 60 and compared their
      protective activities with commercial sunscreens. When a sunscreen of SPF 20, 40
      or 60 was pasted on the plastic cover of a petri dish in which Drosophila larvae
      were exposed to the sun or UV lamps, genotoxicity decreased as the SPF of the
      sunscreen increased, relative to levels of genotoxicity observed in samples
      without sunscreen. However, the protective abilities of sunscreens were
      unexpectedly not so different from each other. To reveal the relationship between
      the protective activity of sunscreen and the wavelength of light with which
      larvae were irradiated through the sunscreen, we measured the transmittance of
      light through the petri dish cover on which the sunscreen was pasted. Effective
      protection was demonstrated by removing components of light whose wavelengths
      were below 315 nm. We suggest, that the measurement of anti-genotoxic activity
      and the determination of the wavelengths of light transmitted through the
      sunscreen should be an alternative method for evaluating the effectiveness of a
      sunscreen.

PMID- 14732253
TI  - Early apoptotic features of K562 cell death induced by 5-aminolaevulinic acid
      based photodynamic therapy.
AB  - 5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) is used to eliminate
      cancerous cells through photoactivation of endogenously formed protoporphyrin IX
      (PPIX) following the administration of PPIX precursor, 5-aminolaevulinic acid
      (ALA). We report on the kinetics of PPIX accumulation and the mechanism of
      cytotoxic effects of ALA-PDT studied in the chronic myelogenous leukaemia derived
      cell line K562. The PPIX distribution and, consequently, cytotoxic effects were
      found to be heterogenous. A subpopulation of K562 cells accumulating PPIX to a
      lesser extent exhibits only transient cell cycle arrest. A fraction of cells,
      probably those with higher PPIX accumulation, are irreversibly damaged by ALA
      PDT. We detected several signs of an early apoptosis: lowering of Bcl-xL
      expression, decrease of the mitochondrial and plasma membrane potential, the
      cytochrome c release into the cytoplasm, and the unmasking of the mitochondrial
      antigen 7A6. However, late apoptotic events were lacking: neither caspase-3
      activation nor DNA fragmentation occurred. Instead, rapidly progressing cell
      necrosis resulting from plasma membrane damage was observed. We suggest that the
      high level of the antiapoptotic heat-shock proteins HSP70 and HSP27 found by us
      in the K562 cells is responsible for the inhibition of the apoptotic process
      upstream of caspases activation.

PMID- 14732254
TI  - Photoinhibition of photosystem I is accelerated by dimethyldithiocarbamate, an
      inhibitor of superoxide dismutase, during light-chilling of spinach leaves.
AB  - In vivo photoinhibition of photosystem I (PS I) was investigated at chilling
      temperature using the leaves of the chilling-resistant spinach plant treated with
      an inhibitor of superoxide dismutase, diethyldithiocarbamate (DDC). When spinach
      leaves were treated with DDC during chilling at 4 degrees C for 12 h with a light
      intensity of 120 micromol m(-2) s(-1), the activity of PS I and the content of
      iron-sulfur centers declined to about 50% and 25% of the non-DDC-treated
      controls, respectively. A native green gel analysis of thylakoid membranes
      isolated from the DDC-treated leaves resolved a novel chlorophyll-protein
      complex, which was identified as the light-harvesting complex I (LHC I)-deficient
      PS I complex when examined by 77 K fluorescence spectroscopy and two-dimensional
      sodium dodecyl sulfate gel electrophoresis. The possible dissociation of LHC I as
      an early structural change in the PS I complex after DDC-induced photoinhibition
      of PS I is discussed.

PMID- 14732255
TI  - Variable fluorescence parameters in the filamentous Patagonian rhodophytes,
      Callithamnion gaudichaudii and Ceramium sp. under solar radiation.
AB  - The filamentous rhodophytes Callithamnion gaudichaudi Agardh and Ceramium sp.
      were utilized to study the effects of solar radiation (PAR, 400-700 nm, UV-B, 280
      315 nm and UV-A, 315-400 nm) on the photosynthetic performance in situ in
      Patagonia waters (Argentina). A pulse amplitude modulated (PAM) fluorometer was
      used to determine the fluorescence parameters. The two species grew in different
      habitats in the eulittoral: Ceramium sp. was found only in rock pools while C.
      gaudichaudii grew on exposed rocks and fell dry during low tide. Both species
      differed in their fluorescence parameters and their sensitivity to solar
      radiation exposure. The photosynthetic quantum yield had its lowest values at
      noon, but it recovered in the afternoon/evening hours, when irradiances were
      lower. PAR (irradiance of about 400 W m(-2) at noon) was responsible for most of
      the decrease in the yield on clear days, especially in Ceramium sp., but UVR (280
      400 nm) also accounted for a significant decrease. Fluence rate response curves
      indicated that both species were adapted to low fluence rates and showed a
      pronounced non-photochemical quenching at intermediate and higher irradiances.
      Both species showed a rapid adaptation during measurement of fast induction
      kinetics but differed significantly in their fluorescence components. All
      photosynthetic pigments were bleached after 8 h exposure to solar radiation over
      a full day. Strong absorption in the UV-A range, most likely due to mycosporine
      like amino acids, was detected in both strains. The pronounced sensitivity to
      solar radiation in situ and the recovery capacity of these two filamentous
      Rhodophyte species, as well as the presence of protective compounds, suggests
      that these algae have the ability to adapt to the relatively high radiation
      levels and changes in irradiance found in the Patagonia waters.

PMID- 14732256
TI  - 9-Hydroxypheophorbide alpha-induced apoptotic death of MCF-7 breast cancer cells
      is mediated by c-Jun N-terminal kinase activation.
AB  - Recently, we synthesized 9-hydroxypheophorbide alpha (9-HPbD), a new chlorophyll
      derived photosensitizer. The photo-treatment of MCF-7 human breast cancer cells
      with 20 kJ/m2 of red light after 5 microM 9-HPbD pretreatment induced cell death,
      showed typical apoptotic features, i.e., chromatin condensation, phosphatidyl
      serine externalization, membrane blebbing, and apoptotic bodies with an intact
      plasma membrane structure. To elucidate the mechanism of 9-HPbD-induced
      apoptosis, various mediators of the apoptosis were investigated. Release of
      cytochrome c from mitochondria into the cytosol was distinct 9 h after
      irradiation, while the levels of most apoptosis-related molecules such as Fas,
      FasL, Bcl-2, Bax and p53 were unchanged. Furthermore, caspase-9 activated by
      released cytochrome c was not significantly activated after 9-HPbD
      photosensitization. On the other hand, stress-activated protein kinases such as
      p38 and c-Jun N-terminal kinase (JNK) were activated 1 h after irradiation.
      Blocking of JNK signaling by transfecting with the dominant negative from of the
      JNK gene significantly reduced 9-HPbD-induced cell death. Our data show that
      photosensitization with the new photosensitizer 9-HPbD could induce the apoptotic
      death of MCF-7 breast cancer cell and that this death is mediated by stress
      activated signal through JNK.

PMID- 14732257
TI  - 2003 Asilomar meeting report.

PMID- 14732258
TI  - Identification of Alternaria brassicicola genes expressed in planta during
      pathogenesis of Arabidopsis thaliana.
AB  - Alternaria brassicicola is a necrotrophic fungal pathogen that causes black spot
      disease on cruciferous plants including economically important Brassica species.
      The purpose of this study was to identify fungal genes expressed during infection
      of Arabidopsis. In order to identify candidate genes involved in pathogenicity,
      we employed suppression subtractive hybridization (SSH) between RNA isolated from
      A. brassicicola spores incubated in water and on the leaf surface of the
      Arabidopsis ecotype Landsberg. Two populations of cDNA were created from total
      RNA extracted after 24h when approximately 80% of the spores had germinated
      either on the leaf surface or in water. Following SSH, expression of clones was
      examined using dot-blot macro-arrays and virtual Northern blots. 47 cDNA clones
      differentially expressed between Alternaria infected Arabidopsis leaves and spore
      germination in water were selected for sequencing. Seventy-seven percent (36) of
      the cDNAs had significant homology to fungal sequences from databases examined,
      including available fungal genomes, while 13% (11) had no homology to sequences
      in the databases. All 36 genes had significant matches with genes of fungal
      origin, while 11 genes did not have significant hits in the databases examined.
      Five sequences were expressed on the plant leaf surface but not during spore
      germination in water according to virtual Northern blots. These five cDNAs were
      predicted to encode a cyanide hydratase, arsenic ATPase, formate dehydrogenase,
      major Alternaria allergen, and one unknown. RT-PCR was used to examine the
      expression of these five genes during infection of Brassica oleraceae var.
      capitata (cabbage), in vitro growth in nutrient rich media, and infection of
      Arabidopsis thaliana. Four of these genes are expressed in the nutrient rich
      medium, while the unknown gene P3F2 was only expressed during plant infection.
      The results of this study provide the first insight into genes expressed during
      A. brassicicola infection of Brassica species that may be involved in fungal
      pathogenesis.

PMID- 14732259
TI  - Aspergillus fumigatus rasA and rasB regulate the timing and morphology of asexual
      development.
AB  - Expression of rasA plays an important role in conidial germination in Aspergillus
      nidulans. Conidial germination is required to initiate both infection and asexual
      development in the opportunistic pathogen Aspergillus fumigatus. Therefore, we
      sought to determine the requirements for Ras proteins in conidial germination and
      asexual development of A. fumigatus. A second homolog, rasB, has been identified
      that characterizes a new subclass of Ras genes. Dominant active (DA) and dominant
      negative (DN) mutations of each gene were introduced into protoplasts as
      transgenes. DArasA expression led to reduced conidiation, malformed
      conidiophores, and altered mitotic progression, whereas expression of DNrasA
      caused a significant reduction in the rate of conidial germination. In contrast,
      expression of DNrasB slightly delayed the initiation of germination and caused
      the development of conidiophores in submerged culture. DArasB expression led to
      reduced conidiation. RasA and RasB appear to play different, but overlapping,
      roles in the vegetative growth and asexual development of A. fumigatus.

PMID- 14732260
TI  - Production of a cell wall-associated endopolygalacturonase by Colletotrichum
      lindemuthianum and pectin degradation during bean infection.
AB  - The bean pathogen Colletotrichum lindemuthianum expresses two
      endopolygalacturonase genes, CLPG1 and CLPG2, during interaction with its host
      plant. However, only CLPG1 was found to be secreted to the extracellular medium
      during saprophytic growth of the fungus on pectin. To localize CLPG2, a FLAG
      epitope sequence was inserted in the C-terminal sequence of CLPG2 and the
      modified gene was introduced into C. lindemuthianum. Western blot analysis using
      a FLAG monoclonal antibody allowed the detection of CLPG2 in intracellular
      protein extracts and in the cell wall fraction, but not in the culture medium.
      Indirect immunofluorescence microscopy was performed to detect CLPG2 during
      saprophytic or parasitic growth. According to the expression pattern of CLPG2, it
      was found that CLPG2 accumulates in the fungal cell wall during growth on pectin
      medium and during appressorium formation, both in vitro and during interaction
      with the plant. Pectin degradation was not detected around the infection peg
      using the monoclonal antibody JIM7, specific for methyl-esterified galacturonan.
      However, extensive pectin dissolution was observed during the development of
      secondary hyphae.

PMID- 14732261
TI  - A putative high affinity hexose transporter, hxtA, of Aspergillus nidulans is
      induced in vegetative hyphae upon starvation and in ascogenous hyphae during
      cleistothecium formation.
AB  - Fungi employ different carbohydrate uptake systems to adapt to certain
      environmental conditions and to different carbon source concentrations. The
      hydrolysis of polymeric carbohydrates and the subsequent uptake of monomeric
      forms may also play a role in development. Aspergillus nidulans accumulates cell
      wall components during vegetative growth and degrades them during sexual
      development. We have identified the hxtA (high affinity hexose transporter) gene
      in a differential library, which was enriched for sexual-specific genes. The hxtA
      gene is disrupted by 6 introns and predicted to encode a 531 amino acid protein
      with high similarity to major facilitator superfamily members including the high
      affinity hexose transporter Gtt1 from Trichoderma harzianum. A. nidulans HxtA
      contains the 12 predicted transmembrane domains characteristic for this family.
      Deletion of hxtA did not impair growth of A. nidulans on a variety of carbon
      sources nor did it inhibit sexual development suggesting redundant sugar uptake
      systems. We found at least 17 putative hexose transporters in the genome of A.
      nidulans. Despite the high similarity of HxtA to fungal high affinity glucose
      transporters, the hxtA gene did not restore growth on glucose of a Saccharomyces
      cerevisiae mutant, in which all hexose transporters were deleted. Northern blot
      analysis revealed that the A. nidulans hxtA gene was repressed under high glucose
      conditions and expressed in vegetative hyphae upon carbon starvation and during
      sexual development. We found hxtA(p)::sgfp expression in developing cleistothecia
      specifically in ascogenous hyphae and propose that HxtA is a high affinity
      glucose transporter involved in sugar metabolism during sexual development.

PMID- 14732262
TI  - Enolase from the ectomycorrhizal fungus Tuber borchii Vittad.: biochemical
      characterization, molecular cloning, and localization.
AB  - Enolase from Tuber borchii mycelium was purified to electrophoretical homogeneity
      using an anion-exchange and a gel permeation chromatography. Furthermore, the
      corresponding gene (eno-1) was cloned and characterized. The purified enzyme
      showed a higher affinity for 2-PGA (0.26 mM) with respect to PEP; the stability
      and activity of enolase were dependent of the divalent cation Mg2+. T. borchii
      eno-1 has an ORF of 1323 bp coding for a putative protein of 440 amino acids and
      Southern blotting analysis revealed that the gene is present as a single copy in
      T. borchii. The enzymatic activity and the mRNA expression level evaluated in
      mycelia grown either in different carbon sources, in pyruvate or during
      starvation were the same in all the conditions tested, while biochemical and
      Northern blotting analyses performed with mycelia at different days of growth
      showed T. borchii eno-1 regulation in response to the growth phase. Finally,
      Western blotting analysis demonstrated that enolase is localized only in the
      cytosolic fraction confirming its important role in glycolysis.

PMID- 14732263
TI  - Genetic damage following introduction of DNA in Phycomyces.
AB  - Introduction of plasmids in Phycomyces blakesleeanus caused extensive changes in
      the exogenous DNA and in the resident genome. Plasmids with a bacterial gene for
      geneticin resistance under a Phycomyces promoter were either injected into
      immature sporangia or incubated with spheroplasts. An improved method produced
      about one viable spheroplast per cell. Colonies resistant to geneticin were rare
      and only about 0.1% of their spores grew in the presence of geneticin. The
      transformation frequency was very low, < or =1 transformed colony per million
      spheroplasts or per microg DNA. Few nuclei in the transformants contained
      exogenous DNA, as shown by a selective procedure that sampled single nuclei from
      heterokaryons. The exogenous DNA was not integrated into the genome and no stable
      transformants were obtained. The plasmids were replicated in the recipient cells,
      but their DNA sequences were modified by deletions and rearrangements and the
      transformed phenotype was eventually lost. The spores developed in injected
      sporangia were often inviable; a genetic test showed that spore death was caused
      by impaired nuclear proliferation and induction of lethal mutations. About one
      fourth of the viable spores from injected sporangia formed abnormal colonies with
      obvious changes in shape, texture, or color. The abnormalities that could be
      investigated were due to dominant mutations. The results indicate that incoming
      DNA is not only attacked, but signals a situation of stress that leads to
      increased mutation and nuclear and cellular death.

PMID- 14732264
TI  - Selection arena in Aspergillus nidulans.
AB  - The selection arena hypothesis states that overproduction of zygotes--a
      widespread phenomenon in animals and plants--can be explained as a mechanism of
      progeny choice. As a similar mechanism, the ascomycetous fungus Aspergillus
      nidulans may overproduce dikaryotic fruit initials, hereafter called dikaryons.
      Then, progeny choice might involve selection on which of these dikaryons will
      thrive to produce thousands of zygotes. These zygotes each produce eight sexual
      spores which together fill up one fruiting body. In this study, we test the
      selection arena hypothesis in this homothallic fungus that produces both sexual
      and asexual spores. We analyzed two mitochondrial and 15 auxotrophic mutations
      for consequences on sexual and asexual reproduction. We found that many of these
      mutations confer sexual self-sterility as a pleiotropic effect under conditions
      of normal asexual spore production. This confirms an important prediction of the
      selection arena, namely that dikaryons carrying a (slightly) deleterious mutation
      are not able to proliferate and produce sexual spores. The selection arena
      ensures that reproductive energy is invested mainly in dikaryons and thus sexual
      spores of good genetic quality.

PMID- 14732265
TI  - The determinant step in ergot alkaloid biosynthesis by an endophyte of perennial
      ryegrass.
AB  - Many cool-season grasses harbor fungal endophytes in the genus Neotyphodium,
      which enhance host fitness, but some also produce metabolites--such as ergovaline
      -believed to cause livestock toxicoses. In Claviceps species the first step in
      ergot alkaloid biosynthesis is thought to be dimethylallyltryptophan (DMAT)
      synthase, encoded by dmaW, previously cloned from Claviceps fusiformis. Here we
      report the cloning and characterization of dmaW from Neotyphodium sp. isolate
      Lp1, an endophyte of perennial ryegrass (Lolium perenne). The gene was then
      disrupted, and the mutant failed to produce any detectable ergovaline or simpler
      ergot and clavine alkaloids. The disruption was complemented with the C.
      fusiformis gene, which restored ergovaline production. Thus, the biosynthetic
      role of DMAT synthase was confirmed, and a mutant was generated for future
      studies of the ecological and agricultural importance of ergot alkaloids in
      endophytes of grasses.

PMID- 14732266
TI  - Use of expressed sequence tag analysis and cDNA microarrays of the filamentous
      fungus Aspergillus nidulans.
AB  - The use of microarrays in the analysis of gene expression is becoming widespread
      for many organisms, including yeast. However, although the genomes of a number of
      filamentous fungi have been fully or partially sequenced, microarray analysis is
      still in its infancy in these organisms. Here, we describe the construction and
      validation of microarrays for the fungus Aspergillus nidulans using PCR products
      from a 4092 EST conidial germination library. An experiment was designed to
      validate these arrays by monitoring the expression profiles of known genes
      following the addition of 1% (w/v) glucose to wild-type A. nidulans cultures
      grown to mid-exponential phase in Vogel's minimal medium with ethanol as the sole
      carbon source. The profiles of genes showing statistically significant
      differential expression following the glucose up-shift are presented and an
      assessment of the quality and reproducibility of the A. nidulans arrays
      discussed.

PMID- 14732267
TI  - A mutation in the Neurospora crassa actin gene results in multiple defects in tip
      growth and branching.
AB  - Actin has a pivotal function in hyphal morphogenesis in filamentous fungi, but it
      is not certain whether its function is equivalent to that of a morphogen, or if
      it is simply part of a mechanism that executes orders given by another regulatory
      entity. To address this question we selected for cytochalasin A resistance and
      isolated act1, the first actin mutant in Neurospora crassa. This mutant branches
      apically and shows an altered distribution of actin at the tip. Based on the
      properties of this mutant, we propose a model of tip growth and branching in
      which actin effects tip growth by regulating the rate of vesicle flow from
      proximal to distal regions of a hypha, thereby controlling the tip-high gradient
      of cytoplasmic calcium. The actin-controlled calcium gradient at the tip is
      necessary for maintenance of tip growth as well as the dominance of one polarized
      site at the hyphal tip. The phenotype of act1 indicates that actin controls the
      balance between lateral and apical branching.

PMID- 14732269
TI  - Molecular cloning and characterization of two different cDNAs encoding the
      molecular chaperone Hsp90 in the oomycete Achlya ambisexualis.
AB  - The chaperone Hsp90 plays a key role in the maturation and activation of many
      'client' proteins in eukaryotic cells. In the oomycete Achlya ambisexualis two
      populations of hsp90 transcripts that differ slightly in size (2.8 and 2.9 kb)
      are present in heat-shocked mycelia. Only the 2.8 kb transcripts are seen in
      vegetative mycelia and in mycelia undergoing antheridiol-induced differentiation.
      Two different hsp90 cDNAs were isolated and characterized. Although nearly
      identical, an additional eight nucleotide sequence was present at the end of the
      3'UTR of one of the two cDNAs. RT-PCR analyses indicated that hsp90 transcripts
      containing the eight nucleotide extension, were present only in heat-shocked
      mycelia. Hsp90 transcripts lacking this sequence were present in vegetative
      mycelia and the levels of these transcripts increased in both heat-shocked and
      hormone-treated mycelia. Each hsp90 cDNA encoded a nearly identical Hsp90
      protein. However, two Hsp90 proteins (86 and 84 kDa) were observed on immunoblots
      of mycelial proteins. Only one of these, i.e., the 86 kDa protein was detected by
      an anti-phosphoserine antibody, suggesting that the difference in mass of the two
      Hsp90 isoforms, was due at least in part, to different levels of phosphoserine
      residues.

PMID- 14732268
TI  - Phylogenetic analysis of globally distributed Mycosphaerella graminicola
      populations based on three DNA sequence loci.
AB  - DNA sequence data from three nuclear loci were collected from 384 isolates
      representing fourteen globally distributed populations of the plant pathogenic
      fungus Mycosphaerella graminicola. Gene genealogies were constructed for the
      actin and beta-tubulin loci as well as for the previously characterized RFLP
      locus STS2. The STS2 and beta-tubulin loci showed greater potential for
      phylogenetic studies than the actin locus. Greater sequence diversity was found
      in the "Old World" populations (Middle East and Europe) than in the "New World"
      populations (North and South America and Australia). The gene trees were rooted
      using homologous DNA sequences of Septoria passerinii, the closest known relative
      to M. graminicola, as well as coalescent rooting. Based on the rooted trees, a
      tentative phylogenetic history of these populations was inferred. The Middle East
      appears to be the most likely center of origin, while European populations are
      more ancient than New World populations. A test for neutrality indicated that the
      intron in the actin locus could be under selection, while the other two sequence
      loci were neutral.

PMID- 14732270
TI  - The arbuscular mycorrhizal fungus Glomus intraradices is haploid and has a small
      genome size in the lower limit of eukaryotes.
AB  - The genome size, complexity, and ploidy of the arbuscular mycorrhizal fungus
      (AMF) Glomus intraradices was determined using flow cytometry, reassociation
      kinetics, and genomic reconstruction. Nuclei of G. intraradices from in vitro
      culture, were analyzed by flow cytometry. The estimated average length of DNA per
      nucleus was 14.07+/-3.52 Mb. Reassociation kinetics on G. intraradices DNA
      indicated a haploid genome size of approximately 16.54 Mb, comprising 88.36%
      single copy DNA, 1.59% repetitive DNA, and 10.05% fold-back DNA. To determine
      ploidy, the DNA content per nucleus measured by flow cytometry was compared with
      the genome estimate of reassociation kinetics. G. intraradices was found to have
      a DNA index (DNA per nucleus per haploid genome size) of approximately 0.9,
      indicating that it is haploid. Genomic DNA of G. intraradices was also analyzed
      by genomic reconstruction using four genes (Malate synthase, RecA, Rad32, and
      Hsp88). Because we used flow cytometry and reassociation kinetics to reveal the
      genome size of G. intraradices and show that it is haploid, then a similar value
      for genome size should be found when using genomic reconstruction as long as the
      genes studied are single copy. The average genome size estimate was 15.74+/-1.69
      Mb indicating that these four genes are single copy per haploid genome and per
      nucleus of G. intraradices. Our results show that the genome size of G.
      intraradices is much smaller than estimates of other AMF and that the unusually
      high within-spore genetic variation that is seen in this fungus cannot be due to
      high ploidy.

PMID- 14732271
TI  - Monophyly of beta-tubulin and H+-ATPase gene variants in Glomus intraradices:
      consequences for molecular evolutionary studies of AM fungal genes.
AB  - Arbuscular mycorrhizal fungi (AMF) are an ecologically important group of fungi.
      Previous studies showed the presence of divergent copies of beta-tubulin and V
      type vacuolar H+-ATPase genes in AMF genomes and suggested horizontal gene
      transfer from host plants or mycoparasites to AMF. We sequenced these genes from
      DNA isolated from an in vitro cultured isolate of Glomus intraradices that was
      free of any obvious contaminants. We found two highly variable beta-tubulin
      sequences and variable H+-ATPase sequences. Despite this high variation,
      comparison of the sequences with those in gene banks supported a glomeromycotan
      origin of G. intraradices beta-tubulin and H+-ATPase sequences. Thus, our results
      are in sharp contrast with the previously reported polyphyletic origin of those
      genes. We present evidence that some highly divergent sequences of beta-tubulin
      and H+-ATPase deposited in the databases are likely to be contaminants. We
      therefore reject the prediction of horizontal transfer to AMF genomes. High
      differences in GC content between glomeromycotan sequences and sequences grouping
      in other lineages are shown and we suggest they can be used as an indicator to
      detect such contaminants. H+-ATPase phylogeny gave unexpected results and failed
      to resolve fungi as a natural group. beta-Tubulin phylogeny supported
      Glomeromeromycota as sister group of the Chytridiomycota. Contrasts between our
      results and trees previously generated using rDNA sequences are discussed.

PMID- 14732272
TI  - Analysis of the distribution and regulation of three representative subtilase
      genes in sapstaining fungi.
AB  - In order to grow in wood, sapstaining fungi produce multiple proteases.
      Previously we have shown that three groups of subtilases appear to be present in
      sapstaining fungi; however, it is unknown whether these groups have distinct
      physiological roles. A representative gene from each of the three groups was
      chosen and the copy number and presence of homologous genes in other sapstaining
      fungi were determined. As well, the expressional regulation of these genes was
      determined in response to available nutrients, exogenous pH, and culture age.
      Gene homologues in the Ofloc1 group were common in Ophiostoma species. However,
      homologues from the Opic group were found in only certain Ophiostoma species. Cr
      group homologues were found in all of the species tested, except for Ophiostoma
      piceae. The expression of opil1, an Ofloc1 group gene, was induced by BSA,
      regulated by pH, and expressed within 12h of induction by BSA. The expression of
      the opic gene, an Opic group gene, was induced by BSA but required the removal of
      either nitrogen or carbon repression, was also regulated by pH, and was expressed
      within 24h of BSA induction. The Cr group gene opil2 was expressed under all
      conditions tested.

PMID- 14732274
TI  - Eicosapentaenoic acid: biosynthetic routes and the potential for synthesis in
      transgenic plants.
AB  - Long chain polyunsaturated fatty acids are now known to play important roles in
      human health. In particular, eicosapentaenoic acid (20:5Delta(5,8,11,14,17); n-3:
      EPA) is implicated as a protective agent in a range of pathologies such as
      cardiovascular disease and Metabolic Syndrome (Syndrome X). Eicosapentaenoic acid
      is currently sourced from fish oils, the presence of this fatty acid being due to
      the dietary piscine consumption of EPA-synthesising micro-algae. The biosynthetic
      pathway of EPA has been elucidated, and contains several alternative metabolic
      routes. Progress in using "reverse engineering" to transgenically mobilize the
      trait(s) for EPA are considered. In particular, the prospect of producing this
      important polyunsaturated fatty acid in transgenic oilseeds is highlighted, as is
      the urgent need for a sustainable replacement for diminishing fish stocks.

PMID- 14732275
TI  - cis-3-Hexenal production in tobacco is stimulated by 16-carbon monounsaturated
      fatty acids.
AB  - Transgenic tobacco plants O9 and T16 expressing the yeast acyl-CoA Delta9
      desaturase and an insect acyl-CoA Delta11 desaturase, respectively, displayed
      altered profiles of fatty acids compared to wild-type tobacco plants and marked
      increases in cis-3-hexenal, a major leaf volatile derived from alpha-linolenic
      acid (18:3). As expected, O9 and T16 plants had increased levels of the major
      unsaturated fatty acid products formed by the transgenic desaturases they
      expressed, viz., palmitoleic acid (16:1(Delta9)) and palmitvaccenic acid
      (16:1(Delta11)), respectively. In addition, levels of 18:3 lipid declined
      slightly and the pool of free 18:3, which accounts for about 30% of free fatty
      acids in wild-type plants, disappeared completely in both transgenics. Both O9
      and T16 plants were found to have a two-fold increase in 13-lipoxygenase (13-LOX)
      activity, which catalyzes the first of two steps leading to hexenal production
      from 18:3. In O9 and T16 plants, the activity of 9-lipoxygenase and hydroperoxide
      lyase, the latter catalyzing the formation of cis-3-hexenal from alpha-linolenic
      acid hydroperoxide, was significantly different from that of the wild-type
      plants. Although 16:1(Delta9) and 16:1(Delta11) had no direct effects on 13-LOX
      activity in vitro, cis-3-hexenal production increased in tobacco leaves treated
      with these fatty acids, suggesting that they may act in vivo by stimulating 13
      LOX gene expression.

PMID- 14732276
TI  - Agrobacterium tumefaciens AK-6b gene modulates phenolic compound metabolism in
      tobacco.
AB  - The 6b gene (AK-6b) of Agrobacterium tumefaciens AKE10 can substitute for the
      requirement of tobacco tissues for auxin and cytokinin to maintain callus growth
      in the culture medium. To identify compounds that might be involved in this
      process we analyzed phenolic metabolites in transgenic tobacco tissues expressing
      the AK-6b gene. On medium containing both cytokinin and auxin (SH medium),
      transgenic calli accumulated higher levels of chlorogenic acid, caffeoyl
      putrescine, rutin and kaempferol-3-rutinoside, than did wild-type tissues. In
      contrast, the levels of scopolin and its aglycone, scopoletin were lower in
      transgenic tissues. On hormone-free medium, these phenolic compounds showed
      neither significant levels nor an apparent relationship with AK-6b transcript
      levels, except for the negatively correlated levels of scopoletin and AK-6b
      transcripts. Apparently, the AK-6b gene acts, in SH medium, to redirect the
      synthesis of scopolin in tobacco tissues towards the preferential synthesis of
      caffeic acid derivatives and flavonoids.

PMID- 14732277
TI  - Beta-adenosine, a bioactive compound in grass chaff stimulating mushroom
      production.
AB  - Fructification and yield of the edible mushrooms Pleurotus pulmonarius and
      Stropharia rugosoannulata are clearly enhanced when wheat straw is supplemented
      with 30% Lolium perenne grass chaff. The bioactive compound in the methanol
      extract of grass chaff was identified as beta-adenosine. In vitro biological
      activity tests showed that 0.012 mg of beta-adenosine per ml of medium stimulated
      earlier fructification of Pleurotus pulmonarius. Mushroom fruiting trials showed
      that when 12 mg beta-adenosine was added to 1 kg wet wheat straw, primordia of
      Pleurotus pulmonarius appeared two days earlier and primordia of Stropharia
      rugosoannulata appeared 18 days earlier when compared to pure wheat straw
      substrate. This concentration of beta-adenosine had no impact on the mushroom
      yield of Pleurotus, but resulted in a 2.2 fold increase in yield for Stropharia.
      beta-Adenosine at 25 mg per kg wet wheat straw increased the yield of Pleurotus
      with 52% and the yield of Stropharia with 258%, but this concentration delayed
      primordial formation in Pleurotus.

PMID- 14732278
TI  - Studies on structure-activity relationship of sphaeropsidins A-F, phytotoxins
      produced by Sphaeropsis sapinea f. sp. cupressi.
AB  - Six forms of sphaeropsidins (SA-SF), three- and tetra-cyclic unrearranged
      pimarane diterpenes produced by Sphaeropsis sapinea f. sp. cupressi, as well as
      eight derivatives obtained by chemical modification of SA-SC, were assayed for
      their bioactivity. The effect of each compound on plants which are host or non
      host of the pathogen was investigated. Activity on some plant pathogenic fungi
      was also tested. Some structure-activity relationships have been identified for
      both phytotoxic and antifungal activity. It appears that the integrity of the
      tricyclic pimarane system, the preservation of the double bond C(8)-C(14), the
      tertiary hydroxyl group at C-9, the vinyl group at C-13, and the carboxylic group
      at C-10 as well as the integrity of the A-ring provide these molecules with non
      selective phytotoxic and antimycotic activity.

PMID- 14732279
TI  - Sesquiterpenes of the liverwort Scapania undulata.
AB  - The essential oil of the liverwort Scapania undulata, collected in the Harz
      mountains, Northern Germany, was analysed by gas chromatography (GC), GC-mass
      spectrometry (MS) and several new components were isolated and investigated by
      various NMR techniques. As new natural compounds the sesquiterpene hydrocarbons
      (+)-helminthogermacrene (1) [the 4Z-isomer of germacrene A (9)], (-)-cis-beta
      elemene (2) as a Cope-rearrangement product of 1, (+)-beta-isolongibornene (3)
      and (-)-perfora-1,7-diene (4) could be identified. 1 has an identical mass
      spectrum and identical GC retention time on a non-polar stationary phase as
      germacrene A (9) but is considerably more stable than the latter. The Cope
      rearrangement of 1 proceeds slowly at 350 degrees C and (-)-cis-beta-elemene (2)
      is formed together with small amounts of other diastereoisomers.

PMID- 14732280
TI  - Neolignan and flavonoid glycosides in Juniperus communis var. depressa.
AB  - Two neolignan glycosides (junipercomnosides A and B) were isolated from aerial
      parts of Juniperus communis var. depressa along with two known neolignan
      glycosides and seven flavonoid glycosides. The structures of the isolated
      compounds were determined by spectral analysis, in particular by 2D-NMR analysis.
      The significance of distribution of flavonoids in the chemotaxonomy of genus
      Juniperus was also discussed.

PMID- 14732281
TI  - Trimeric proteracacinidins and a (6-->6)-bis-leucoteracacinidin from Acacia
      galpinii and Acacia caffra.
AB  - The rare series of trimeric proteracacinidins is extended by identification of
      the first analogs with exclusive C-C interflavanyl bonds, i.e. epioritin-(4beta-
      >6)-oritin-(4alpha-->6)-epioritin-4alpha-ol,oritin-(4beta-->6)-oritin-(4alpha-
      >6)-epioritin-4alpha-ol, and epioritin-(4beta-->6)-epioritin-(4beta-->6)
      epioritin-4alpha-ol. These compounds are accompanied by the bis
      leucoteracacinidin, epioritin-4alpha-ol-(6-->6)-epioritin-4beta-ol, the first
      naturally occurring bis-flavan-3,4-diol.

PMID- 14732282
TI  - Prenylated flavonoids, monoterpenoid furanocoumarins and other constituents from
      the twigs of Dorstenia elliptica (Moraceae).
AB  - A monoprenylated flavan and two monoterpenoid substituted furanocoumarins were
      isolated from the twigs of Dorstenia elliptica along with 3-(3,3-dimethylallyl)
      4,2',4'-trihydroxylchalcone, psoralen, bergapten, O-[3-(2,2-dimethyl-3-oxo-2H
      furan-5-yl)butyl]bergaptol, beta-sitosterol and its beta-D-glucopyranoside. The
      structure of the flavan was determined as 6(1,1-dimethylallyl)-7,4'
      dihydroxylflavan and the monoterpenoid substituted furanocoumarins were assigned
      as O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)-3-hydroxybutyl]-bergaptol and O-[2-(5
      hydroxy-2,6,6-trimethyl-3-oxo-2H-pyran-2-yl)ethyl]bergaptol, respectively, using
      spectroscopic analysis, especially, 2D NMR spectra.

PMID- 14732283
TI  - The caulindoles: dimeric prenylindoles from Isolona cauliflora.
AB  - Four dimeric prenylindoles occurring in diastereomeric pairs, the caulindole A-D,
      5-(3-methyl-2-butenyl)-1H-indole, and (E)-5-(3-methylbuta-1,3-dienyl)-1H-indole
      were isolated from the stem and root barks of Isolona cauliflora, an ecologically
      endangered Annonaceae species. Structural determination was achieved based on
      interpretation of spectroscopic data. Biogenetically, the caulindoles are
      considered as Diels-Alder-type cycloaddition products of mono- and/or bis
      prenylindoles [e.g. 5-(3-methyl-2-butenyl)-1H-indole and (E)-5-(3-methylbuta-1,3
      dienyl)-1H-indole] as the dienes and dienophiles.

PMID- 14732284
TI  - Rapid dereplication of estrogenic compounds in pomegranate (Punica granatum)
      using on-line biochemical detection coupled to mass spectrometry.
AB  - During recent years, phytoestrogens have been receiving an increasing amount of
      interest, as several lines of evidence suggest a possible role in preventing a
      range of diseases, including the hormonally dependent cancers. In this context,
      various parts of the pomegranate fruit (Punica granatum; Punicaceae), e.g. seed
      oil, juice, fermented juice and peel extract, have been shown to exert
      suppressive effects on human breast cancer cells in vitro. On-line biochemical
      detection coupled to mass spectrometry (LC-BCD-MS) was applied to rapidly profile
      the estrogenic activity in the pomegranate peel extract. The crude mixture was
      separated by HPLC, after which the presence of biologically active compounds,
      known or unknown, was detected by means of an on-line beta-estrogen receptor (ER)
      bioassay. Chemical information, such as molecular weight and MS/MS fingerprint,
      was obtained in real time by directing part of the HPLC effluent towards a mass
      spectrometer. Using this approach in total three estrogenic compounds, i.e.
      luteolin, quercetin and kaempferol, were detected and identified by comparing the
      obtained molecular weights and negative ion APCI MS/MS spectra with the data of
      an estrogenic compound library. Although well known in literature and widely
      distributed in nature, the presence of these phytoestrogenic compounds in
      pomegranate peel extract was not reported previously. Compared to traditional
      screening approaches of complex mixtures, often characterized by a repeating
      cycle of HPLC fractionation and biological screening, LC-BCD-MS was shown to
      profoundly accelerate the time required for compound description and
      identification.

PMID- 14732286
TI  - New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman
      metabolites in biology and medicine.
AB  - Vitamin E (alpha-tocopherol or alphaT) has long been recognized as a classic free
      radical scavenging antioxidant whose deficiency impairs mammalian fertility. In
      actuality, alpha-tocopherol is one member of a class of phytochemicals that are
      distinguished by varying methylation of a chroman head group. Early studies
      conducted between 1922 and 1950 indicated that alpha-tocopherol was specific
      among the tocopherols in allowing fertility of laboratory animals. The unique
      vitamin action of alphaT, combined with its prevalence in the human body and the
      similar efficiency of tocopherols as chain-breaking antioxidants, led biologists
      to almost completely discount the "minor" tocopherols as topics for basic and
      clinical research. Recent discoveries have forced a serious reconsideration of
      this conventional wisdom. New and unexpected biological activities have been
      reported for the desmethyl tocopherols, such as gamma-tocopherol, and for
      specific tocopherol metabolites, most notably the carboxyethyl-hydroxychroman
      (CEHC) products. The activities of these other tocopherols do not map directly to
      their chemical antioxidant behavior but rather reflect anti-inflammatory,
      antineoplastic, and natriuretic functions possibly mediated through specific
      binding interactions. Moreover, a nascent body of epidemiological data suggests
      that gamma-tocopherol is a better negative risk factor for certain types of
      cancer and myocardial infarction than is a alpha-tocopherol. The potential public
      health implications are immense, given the extreme popularity of alphaT
      supplementation which can unintentionally deplete the body of gamma-tocopherol.
      These findings may or may not signal a major paradigm shift in free radical
      biology and medicine. The data argue for thorough experimental and
      epidemiological reappraisal of desmethyl tocopherols, especially within the
      contexts of cardiovascular disease and cancer biology.

PMID- 14732287
TI  - Source of early reactive oxygen species in the apoptosis induced by transforming
      growth factor-beta in fetal rat hepatocytes.
AB  - Transforming growth factor-beta (TGF-beta) induces an oxidative stress process in
      hepatocytes that mediates its apoptotic activity. To determine the cellular
      source of the early reactive oxygen species (ROS) generated by fetal rat
      hepatocytes in response to TGF-beta, we used inhibitors that block different ROS
      producing systems. Diphenyleneiodonium, which inhibits NADPH oxidase and other
      flavoproteins, completely blocked the increase in ROS induced by TGF-beta,
      coincidently with an impairment of caspase-3 activation and cell death. Rotenone,
      an inhibitor of the NADH dehydrogenase in mitochondrial complex I, attenuated,
      but did not completely inhibit, ROS-production, caspase activation, and cell
      death mediated by TGF-beta. No significant protection was observed with
      inhibitors of other ROS-producing systems, such as cytochrome P450 (metyrapone),
      cyclooxygenase (indomethacin), and xanthine oxidase (allopurinol). Additional
      experiments have indicated that two different mechanisms could be involved in the
      early ROS production by TGF-beta. First, an inducible (cycloheximide-inhibited)
      NADPH oxidase-like system could account for the extramitochondrial production of
      ROS. Second, TGF-beta could increase ROS by a rapid downregulation of antioxidant
      genes. In particular, intramitochondrial ROS would increase by depletion of
      MnSOD. Finally, glutathione depletion is a late event and it would be more the
      consequence than the cause of the increase in ROS induced by TGF-beta.

PMID- 14732288
TI  - Aging and lifelong calorie restriction result in adaptations of skeletal muscle
      apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis,
      caspase-3, and caspase-12.
AB  - The mechanisms of apoptosis in the loss of myocytes in skeletal muscle with age
      and the role of mitochondrial and sarcoplasmic reticulum-mediated pathways of
      apoptosis are unknown. Moreover, it is unknown whether lifelong calorie
      restriction prevents apoptosis in skeletal muscle and reverses age-related
      alterations in apoptosis signaling. We investigated key apoptotic regulatory
      proteins in the gastrocnemius muscle of 12 and 26 month old ad libitum fed and 26
      month old calorie-restricted male Fischer-344 rats. We found that apoptosis
      increased with age and that calorie-restricted rats showed less apoptosis
      compared with their age-matched cohorts. Moreover, pro- and cleaved caspase-3
      levels increased significantly with age and calorie-restricted rats had
      significantly lower levels than the aged ad libitum group. Neither age nor
      calorie restriction had any effect on muscle caspase-3 enzyme activity, but the
      levels of X-linked inhibitor of apoptosis, particularly an inhibitor of caspase
      3, increased with age and were reduced significantly in the 26 month old calorie
      restricted cohort. The apoptotic inhibitor apoptosis repressor with a caspase
      recruitment domain (ARC), which inhibits cytochrome c release, underwent an age
      associated decline in the cytosol but increased with calorie restriction. In
      contrast, mitochondrial ARC levels increased with age and were lower in calorie
      restricted rats than in age-matched controls, suggesting a translocation of this
      protein to attenuate oxidative stress. The translocation of ARC may explain the
      reduction in cytosolic cytochrome c levels observed with age and calorie
      restriction. Moreover, we found a striking approximately 350% increase in the
      expression of procaspase-12 (caspase located at the sarcoplasmic reticulum) with
      age which was significantly lower in the 26 month old calorie-restricted group.
      The total protein level of apoptosis-inducing factor in the plantaris muscle
      increased with age and was reduced calorie-restricted rats compared with age
      matched controls, but there were no significant changes in this pro-apoptotic
      protein in the isolated nuclei. Calorie restriction is able to lower the
      apoptotic potential in aged skeletal muscle by altering several key apoptotic
      proteins toward cellular survival, thereby reducing the potential for sarcopenia.

PMID- 14732289
TI  - Cytoprotective effects of heme oxygenase-1 induction by 3-O-caffeoyl-1
      methylquinic acid.
AB  - The novel antioxidant 3-O-caffeoyl-one-methylquinic acid (MCGA3) is a methyl
      chlorogenic acid derivative isolated from bamboo leaves. MCGA3 scavenges reactive
      oxygen species (ROS) and inhibits lipid peroxidation and xanthine oxidase in
      vitro. In this study, we evaluated the cytoprotective effect of MCGA3, which
      occurs via heme oxygenase-1 (HO-1) induction in bovine vascular endothelial cells
      exposed to tert-butylhydroperoxide (tBHP). Cells treated with 1 mM tBHP (6-18 h)
      generated substantial ROS and concomitantly lost most intracellular lactate
      dehydrogenase (LDH), which then caused necrotic cell death. Of the several MCGA
      antioxidants and structurally related phenolic acids examined in this study,
      MCGA3 (0.01-0.15 mM) was found to completely block this necrosis and generation
      of ROS by tBHP. Surprisingly, MCGA3 by itself was found to be a potent inducer of
      HO-1. We observed the time- and dose-dependent induction of HO-1 mRNA and
      protein, which was closely associated with decreased intracellular ROS and
      necrosis against tBHP. Deesterified or Al-chelated MCGA3 or co-treatment with
      MCGA3 and actinomycin D abolished HO-1 induction and the antinecrotic effect of
      MCGA3. Zinc protoporphyrin IX and cycloheximide attenuated the cytoprotection
      afforded by MCGA3, but did not reduce HO-1 mRNA. Interestingly, N-acetylcysteine
      (1 mM) enhanced the HO-1 induction of MCGA3, but N-acetylcysteine itself did not
      induce HO-1. These results suggested that not only ortho-dihydroxyl groups but
      also aromatic ester and methoxyl ester moieties are necessary for full HO-1
      induction and cytoprotection against toxic tBHP-derived ROS. Ferritin mRNA was
      also upregulated during all HO-1 induction by MCGA3, which might decrease iron
      and lower ROS levels. Consequently, the combined action of HO-1 and ferritin may
      protect cells from toxic tBHP-mediated necrosis.

PMID- 14732290
TI  - Fibroblasts derived from Gpx1 knockout mice display senescent-like features and
      are susceptible to H2O2-mediated cell death.
AB  - The Free Radical Theory of Aging proposes that reactive oxygen species (ROS)
      contribute to the pathophysiology of aging. Our previous data highlight the
      importance of antioxidant enzymes, superoxide dismutase 1 (Sod1) and glutathione
      peroxidase 1 (Gpx1), in regulating this process. Previously, we demonstrated that
      a perturbation in the Sod1-to-Gpx1 ratio, as a consequence of Sod1
      overexpression, leads to senescence-like changes. We proposed that this was
      mediated via the Sod1 dismutation product H2O2, because H2O2 induced similar
      changes in control cells. However, it has been suggested that H2O2 production,
      via Sod1 dismutation, is rate-limited by the availability of the substrate O2*-,
      and therefore age-related changes may occur as a result of other functions of
      Sod1. In this study, we test this notion in fibroblasts derived from Gpx1 null
      mutant mice (Gpx1-/-) that have elevated H2O2 as a consequence of the lack of its
      removal by Gpx1. We demonstrate senescence-like changes in Gpx1-/- fibroblasts
      that include (1) reduced proliferative capacity, DNA synthesis, and
      responsiveness to EGF and serum; (2) elevated levels of Cip1; (3) increased NF
      kappaB activation; and (4) morphological features of senescent cells. Gpx1-/-
      fibroblasts also demonstrate a dose-dependent susceptibility to H2O2-induced
      apoptosis. Our findings suggest that Gpx1 is protective against both ROS-mediated
      senescence-like changes and oxidant-mediated cell death.

PMID- 14732291
TI  - Overexpression of human peroxiredoxin 5 in subcellular compartments of Chinese
      hamster ovary cells: effects on cytotoxicity and DNA damage caused by peroxides.
AB  - Peroxiredoxin 5 is a mammalian thioredoxin peroxidase ubiquitously expressed in
      tissues. Peroxiredoxin 5 can be intracellularly localized to mitochondria,
      peroxisomes, the cytosol, and, to a lesser extent, the nucleus. This remarkably
      wide subcellular distribution compared with the five other mammalian
      peroxiredoxins prompted us to further investigate the antioxidant protective
      function of peroxiredoxin 5 in mammalian cells according to its subcellular
      localization. Chinese hamster ovary cells overexpressing human peroxiredoxin 5 in
      the cytosol, in mitochondria, or in the nucleus were established by stable
      transfection. Cells overexpressing peroxiredoxin 5 were exposed for 1 h to low or
      acute oxidative stress with exogenously added hydrogen peroxide or tert
      butylhydroperoxide. Cell protection conferred by peroxiredoxin 5 was evaluated by
      clonogenicity and lactate dehydrogenase assays. Overexpressing peroxiredoxin 5 in
      either the cytosolic, mitochondrial, or nuclear compartment significantly reduced
      cell death, with more effective protection with overexpression of peroxiredoxin 5
      in mitochondria, confirming that this organelle is a major target of peroxides.
      Moreover, we evaluated, with the comet assay, nuclear DNA damage induced by
      hydrogen peroxide or tert-butylhydroperoxide. Overexpression of peroxiredoxin 5
      in the nucleus significantly decreased DNA damage induced by both peroxides. In
      conclusion, the present study suggests that multiple subcellular targeting of
      peroxiredoxin 5 in mammalian cells can be implicated in antioxidant protective
      mechanisms under nonpathological conditions but also during acute oxidative
      stress caused by peroxides occurring in pathophysiological situations.

PMID- 14732292
TI  - Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit
      lungs during ischemia.
AB  - Increases in free radicals are believed to play a central role in the development
      of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage
      and deterioration of pulmonary surfactant. Continued ventilation during ischemia
      offers significant protection against I-R injury, but the impact of alveolar
      oxygen supply both on lung injury and on radical generation is still unclear. We
      investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation
      during ischemia on alveolar antioxidant status and surfactant properties in
      isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs
      (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with
      controls, biophysical and biochemical surfactant properties were not altered in
      anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment
      of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E),
      retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O
      alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a
      significant increase in antioxidant compounds under anoxic and hyperoxic
      ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH
      increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic
      ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated
      ischemia compared with native controls (1.3 +/- 0.2 microM), but did not
      significantly change under anoxic and hyperoxic ventilation alone. In parallel,
      under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic
      (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h:
      0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02
      microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/-
      15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with
      native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in
      the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic
      ventilation. This is paralleled by an increase rather than a decrease in alveolar
      antioxidant levels, suggested to reflect an adaptive response to oxidative stress
      during ischemia.

PMID- 14732293
TI  - Direct oxidation of 2',7'-dichlorodihydrofluorescein by pyocyanin and other redox
      active compounds independent of reactive oxygen species production.
AB  - Formation of dichlorofluorescein (DCF), the fluorescent oxidation product of
      2',7'-dichlorodihydrofluorescein (DCFH2), in cells loaded with the latter
      compound is often used to detect ROS formation. We previously found that exposure
      of DCFH2-loaded A549 cells to the Pseudomonas aeruginosa secretory product
      pyocyanin results in DCF formation, consistent with ROS production. However,
      since pyocyanin directly accepts electrons from NAD(P)H, we hypothesized that
      pyocyanin might directly oxidize DCFH2 to DCF without an ROS intermediate.
      Incubation of DCFH2 with pyocyanin rapidly resulted in DCF formation, the rate of
      which was proportional to the [pyocyanin] and was not inhibited by SOD or
      catalase. Phenazine methosulfate, a pyocyanin analog, was more effective than
      pyocyanin in generating DCF. Mitoxantrone and ametantrone also produced DCF.
      However, menadione, paraquat, plumbagin, streptonigrin, doxorubicin,
      daunorubicin, and 5-iminodaunorubicin did not. Pyocyanin, phenazine methosulfate,
      mitoxantrone, and ametantrone also oxidized dihydrofluorescein and 5- (and 6-) 
      carboxy-2',7'-dichlorodihydrofluorescein, whereas dihydrorhodamine was oxidized
      only by pyocyanin or phenazine methosulfate. Under aerobic conditions, the
      interaction of DCFH2 with pyocyanin or phenazine methosulfate (but not
      mitoxantrone or ametantrone) produced superoxide, as detected by spin trapping.
      Direct oxidation of the fluorescent probes needs to be controlled for when
      employing these compounds to assess ROS formation by biological systems exposed
      to redox active compounds.

PMID- 14732294
TI  - Measurement of NAD(P)H oxidase-derived superoxide with the luminol analogue L
      012.
AB  - In the present study we sought to determine the ability of the chemiluminescence
      dye 8-amino-5-chloro-7-phenylpyridol[3,4-d]pyridazine-1,4-(2H,3H)dione sodium
      salt (L-012) to detect superoxide in different biological systems. In human whole
      blood or isolated leukocytes, the sensitivity of the luminol analogue L-012 to
      detect superoxide was higher as compared with luminol, lucigenin, coelenterazine,
      and the fluorescence dye dihydroethidine. In isolated leukocytes as well as
      aortic rings from control (New Zealand White) and hyperlipidemic (Watanabe
      heritable hyperlipidemic) rabbits, L-012-enhanced chemiluminescence was
      successful in detecting differences in superoxide formation under basal
      conditions and on stimulation with the direct activator of protein kinase C,
      phorbol 12,13-dibutyrate (PDBu). The effects of PDBu were abrogated by gliotoxin
      and inhibitors of protein kinase C such as chelerythrine, identifying NAD(P)H
      oxidase as the significant superoxide source. Experiments using electron
      paramagnetic resonance and the spin trap 5-diethoxyphosphoryl-5-methyl-1
      pyrroline-N-oxide revealed that in contrast to lucigenin, L-012 is not subject to
      redox cycling. These findings indicate that L-012-enhanced chemiluminescence
      represents a sensitive and reliable probe to detect superoxide in whole blood,
      inflammatory cells, and vascular tissue.

PMID- 14732295
TI  - Cell cycle arrest by monochloramine through the oxidation of retinoblastoma
      protein.
AB  - Impairment of cell cycle control has serious effects on inflammation, tissue
      repair, and carcinogenesis. We report here the G1 cell cycle arrest by
      monochloramine (NH2Cl), a physiological oxidant derived from activated
      neutrophils, and its mechanism. When Jurkat cells were treated with NH2Cl (70
      microM, 10 min) and incubated for 24 h, the S phase population decreased
      significantly with a slight increase in the hypodiploid cell population. The G0/
      G1 phase and G2/M phase populations did not show marked changes. Three hours
      after NH2Cl treatment, the retinoblastoma protein (pRB) was dephosphorylated
      especially at Ser780 and Ser795, both of which are important phosphorylation
      sites for the G1 checkpoint function. The phosphorylation at Ser807/811 showed no
      apparent change. The expression of cyclins, cyclin-dependent kinases, and cyclin
      dependent kinase inhibitors showed no apparent change. Moreover, the kinase
      activity that phosphorylates pRB remained constant even after NH2Cl treatment.
      The protein phosphatase activity that dephosphorylates pRB showed a marginal
      increase. Notably, when the recombinant pRB was oxidized by NH2Cl in vitro, the
      oxidized pRB became difficult to be phosphorylated by kinases, especially at
      Ser780 and Ser795, but not at Ser807/811. Amino acid analysis of oxidized pRB
      showed methionine oxidation to methionine sulfoxide. The NH2Cl-treated Jurkat
      cell proteins also showed a decrease in methionine. These observations suggested
      that direct pRB oxidation was the major cause of NH2Cl-induced cell cycle arrest.
      In the presence of 2 mM NH4+, NaOCl (200 microM) or activated neutrophils also
      induced a G1 cell cycle arrest. As protein methionine oxidation has been reported
      in inflammation and aging, cell cycle modulation by pRB oxidation may occur in
      various pathological conditions.

PMID- 14732296
TI  - Coronary endothelial dysfunction is not rapidly reversible with ascorbic acid.
AB  - In humans with cardiovascular risk factors, increased vascular production of
      superoxide anion may contribute to endothelial dysfunction by its reacting with
      nitric oxide and reducing its biological activity. High concentrations of
      ascorbic acid scavenge superoxide anion and restore normal endothelium-dependent
      vasodilation in humans with cardiovascular risk factors. To investigate the
      contribution of increased superoxide anion to endothelial dysfunction in
      atherosclerotic coronary arteries, we examined the effect of sequential infusions
      of ascorbic acid (final concentration 0.1, 1.0, and 10 mmol/L) or placebo on
      coronary endothelial function in 26 subjects referred for cardiac catheterization
      to evaluate coronary artery disease. Coronary vasomotor function was evaluated
      using intracoronary agonist infusion, quantitative angiography, and intracoronary
      Doppler measurements. At baseline, endothelium-dependent vasodilation of
      epicardial arteries and coronary microvessels was impaired to an equivalent
      extent in the ascorbic acid and placebo groups. Sequential ascorbic acid
      infusions had no effect on the acetylcholine-induced change in coronary artery
      diameter (-11+/-8, -12+/-10, and -9+/-9%) compared with the effect of placebo (
      14+/-13, -16+/-10, and -13+/-9%) infusions (p=0.98). Similarly, the changes in
      coronary blood flow during acetylcholine infusions were equivalent during
      ascorbic acid (51+/-44, 67+/-66, and 62+/-52%) and placebo (61+/-104, 55+/-93,
      and 50+/-69%) infusions (p=0.63). Ascorbic acid also had no effect on the dilator
      response to intracoronary nitroglycerin (p=0.19). These data argue against an
      important role for superoxide-mediated "inactivation" of nitric oxide or another
      rapidly reversible form of oxidative stress as a mechanism of coronary
      endothelial dysfunction in patients with coronary atherosclerosis.

PMID- 14732297
TI  - Dissent is a cornerstone of scientific discourse.

PMID- 14732298
TI  - Social variations in fetal growth in a Russian setting: an analysis of medical
      records.
AB  - PURPOSE: The study examines variations in fetal growth by maternal social
      circumstances in a Russian town. METHODS: All pregnant women registered at the
      antenatal clinics in 1999 in Severodvinsk (north-west Russia) and their live born
      infants comprised the study base (n=1399). Multivariate linear regression
      analysis was applied to quantify the effect of socio-demographic factors on
      birthweight and the ponderal index (PI). RESULTS: A clear gradient of birthweight
      in relation to mothers' education was revealed. Babies of the most educated
      mothers were 207 g (95% CI, 55, 358) heavier than babies of mothers with basic
      education. The average weight of those born to mothers with secondary and
      vocational levels of education was 172 g (95% CI, 91, 253) and 83 g (95% CI, 9,
      163) lower compared with infants born to mothers with a university level of
      education after adjustment for age, parity, pre-pregnancy weight, marital status,
      maternal occupation, length of gestation, and sex of the baby. Maternal education
      also influenced the PI. CONCLUSIONS: Further studies should focus on the
      mechanisms of the coherence of maternal education and fetal growth. To ensure
      that all parts of the society benefit equally from economic and social reforms,
      social variations in pregnancy outcomes should be monitored during the time of
      transition.

PMID- 14732299
TI  - The association of psychiatric disorders and HIV infection in the correctional
      setting.
AB  - PURPOSE: Psychiatric disorders, such as bipolar disorder, schizophrenia, and
      depression, have been associated with both HIV-associated risk behaviors and HIV
      infection. While the US prison population is reported to exhibit elevated rates
      of HIV/AIDS and most psychiatric disorders, scarce information currently exists
      on the association of these conditions in the prison setting. The present study
      examined the association of six major psychiatric disorders with HIV infection in
      one of the nation's largest prison populations. METHODS: The study population
      consisted of 336,668 Texas Department of Criminal Justice inmates who were
      incarcerated for any duration between January 1, 1999 and December 31, 2001.
      Information on medical conditions and sociodemographic factors was obtained from
      an institution-wide medical information system. RESULTS: Inmates diagnosed with
      HIV infection exhibited elevated rates of major depression, dysthymia, bipolar
      disorder, schizophrenia, schizoaffective disorder, and non-schizophrenic
      psychotic disorder. These rates persisted in stratified analyses and in a
      multivariate analysis that statistically adjusted for gender, race, and age
      category. CONCLUSION: The present cross-sectional study's finding of a positive
      association between HIV infection and psychiatric diagnoses among inmates holds
      both clinical and public health relevance. It will be important for future
      investigations to prospectively assess the underlying mechanisms of these
      associations in the correctional setting.

PMID- 14732300
TI  - Diabetes mellitus and cognitive performance in older women.
AB  - PURPOSE: This cross-sectional study sought to identify diabetes accurately in a
      study population of 3681 women age 75 and older and to determine the association
      of diabetes with cognitive performance. METHODS: A previously validated test, the
      Telephone Interview of Cognitive Screening-Modified (TICSm) was given to assess
      cognitive status. A diabetes case identification database, medical record review
      and self-report were used to determine diabetes cases. 489 (13.3%) of the women
      in the study were classified with diabetes and 3192 without diabetes. RESULTS: t
      tests and linear regression analyses determined that diabetic women had a mean
      TICSm score 1.4 points lower (i.e. more impaired) than non-diabetic women. Using
      linear regression to adjust for age, education, and vascular disease, diabetic
      women showed a 1.1 lower score on the TICSm. Similar adjustments were made for
      potential confounding variables such as depression, hormone replacement therapy
      (HRT), high body weight, smoking, alcohol use and exercise and diabetics again
      showed a 1.0 lower score. CONCLUSION: This study, which utilizes highly rigorous
      case identification methodology, provides further evidence that diabetes is
      associated with significantly worse cognitive performance in the elderly.

PMID- 14732301
TI  - Neighborhood context and self-rated health in older Mexican Americans.
AB  - PURPOSE: To determine whether neighborhood characteristics are associated with
      self-rated health in older Mexican Americans. METHODS: Epidemiologic data on 3050
      older Mexican Americans residing in the southwestern United States during 1993
      and 1994 were merged with 1990 US Census data. All subjects were matched to one
      of 210 census tracts (neighborhoods). Multilevel ordinal logit models were used
      to examine relationships between self-rated health and individual- and
      neighborhood-level variables. RESULTS: After adjusting for individual
      characteristics, older Mexican Americans were more likely to rate their health
      poorer if they lived in neighborhoods that were economically disadvantaged, less
      populated by other Hispanics, or located within 50 miles of the US-Mexico border.
      In addition, residence in a border community moderated the relationship between
      self-rated health and neighborhood economic disadvantage. The effect of
      neighborhood economic disadvantage on poorer self-rated health was two to three
      times stronger for subjects living near the border region than subjects living
      further away from the border. CONCLUSIONS: This study demonstrates the importance
      of considering several dimensions of neighborhood context, especially for Mexican
      Americans. Residence in a border community and neighborhood economic disadvantage
      were important predictors of poorer self-rated health status. In addition, older
      Mexican Americans experience a health benefit from living in neighborhoods
      populated with other Hispanics.

PMID- 14732302
TI  - Differences between estimated caloric requirements and self-reported caloric
      intake in the women's health initiative.
AB  - PURPOSE: To compare energy intake derived from a food frequency questionnaire
      (FFQ) with estimated energy expenditure in postmenopausal women participating in
      a large clinical study. METHODS: A total of 161,856 women aged 50 to 79 years
      enrolled in the Women's Health Initiative (WHI) Observational Study (OS) or
      Clinical Trial (CT) [including the Diet Modification (DM) component] completed
      the WHI FFQ, from which energy intake (FFQEI) was derived. Population-adjusted
      total energy expenditure (PATEE) was calculated according to the Harris-Benedict
      equation weighted by caloric intakes derived from the National Health and
      Nutrition Examination Survey. Stepwise regression was used to examine the
      influence of independent variables (e.g., demographic, anthropometric) on FFQEI
      PATEE. Race, region, and education were forced into the model; other variables
      were retained if they increased model explanatory ability by more than 1%.
      RESULTS: On average, FFQEI was approximately 25% lower than PATEE. Regression
      results (intercept=-799 kcal/d) indicated that body mass index (b=-23
      kcal/day/kg.m(-2)); age (b=15 kcal/day/year of age); and study arm (relative to
      women in the OS, for DM women b=169 kcal/d, indicating better agreement with
      PATEE) increased model partial R(2)>.01. Results for CT women not eligible for DM
      were similar to those of women in the OS (b=14 kcal/d). There also were apparent
      differences by race (b=-152 kcal/d in Blacks) and education (b=-67 kcal/d in
      women with<high school). CONCLUSION: This large, carefully studied population
      confirms previous observations regarding underestimates in self-reported caloric
      intake relative to estimates of metabolic need in younger women, and those with
      higher weight, with less education, and in Blacks. These differences, along with
      effects related to intervention assignment, underline the need for additional
      research to enhance understanding of errors in dietary measurement.

PMID- 14732303
TI  - Relationships between hormonal status and cataract in french postmenopausal
      women: the POLA study.
AB  - PURPOSE: Prevalence rate of cataract is higher in women than in men. Sex hormones
      have been hypothesized to be linked with this gender difference. Our aim is to
      study the relationships between hormonal status and cataract in postmenopausal
      women. METHODS: The Pathologies Oculaires Liees a l'Age (POLA) study is a
      population-based study on age-related eye diseases and their risk factors, in
      2584 residents of Sete (France). Cataract classification was based on a
      standardized lens examination, according to Lens Opacities Classification System
      III. Biological measurements were performed from fasting blood samples. We
      conducted a cross-sectional study in the female participants (n=1451) aged over
      60 years. RESULTS: No association of hormone replacement therapy (HRT) with any
      type of cataract was found, but an increased risk of cataract surgery was
      observed in women with a long duration of hormone therapy >/=5 years)
      (multivariate-adjusted odds ratio (OR)=3.80; 95% CI: 1.45-9.94). Globally, the
      risk for cataract (any type) was not associated with a long duration of HRT use
      (OR=1.06; 95% CI: 0.64-1.74). After multivariate adjustment, oophorectomy was
      associated with a reduced risk of cataract (OR=0.60; 95% CI=0.38-0.94). In the
      multivariate model, no association was found between estradiol, total
      testosterone or sex-hormone-binding globulin and cataract. However, high levels
      of dehydroepiandrosterone sulfate (DHEAS) were associated with a reduced risk of
      cataract (OR=0.79; 95% CI: 0.63-0.99). CONCLUSION: HRT use was not associated
      with cataract. A reduced risk of cataract was found in oophorectomized women and
      in women with high DHEAS levels.

PMID- 14732304
TI  - The belgrade childhood diabetes study: association of infections and vaccinations
      on diabetes in childhood.
AB  - PURPOSE: The aim of this study was to investigate whether individual infections
      or combination of infections or vaccination affect the risk of developing
      diabetes in childhood. METHODS: A case-control study was conducted in Belgrade
      during the period between 1994 and 1997. A total of 105 recent onset diabetics
      were compared with 210 controls chosen among children with skin disease (the
      first control group). Cases and controls were individually matched by age (+/-1
      year), sex, and place of residence. Eighty-six diabetic children were also
      compared with their brothers/sisters (the second control group). RESULTS: After
      adjustment for confounding variables, independent association with diabetes was
      found for infections during the 6 months preceding the onset of the disease, when
      cases were compared with both the first control group (OR=4.23, 95% CI, 1.95
      9.17, p<0.001) and the second control group (OR=4.68, 95% CI, 2.09-10.47,
      p<0.001), and for regular vaccination when cases were compared with the first
      control group (OR=0.08, 95% CI, 0.01-0.50, p=0.03). CONCLUSION: The results
      obtained support the hypotheses that infections play a role in the development of
      type 1 diabetes and that regular vaccination has a preventive effect.

PMID- 14732305
TI  - A cohort mortality study of workers exposed to chlorinated organic solvents in
      Taiwan.
AB  - PURPOSE: A retrospective cohort mortality study based on standardized mortality
      ratios (SMRs) was conducted to investigate the possible association between
      exposure to chlorinated organic solvents and various types of cancer deaths.
      METHODS: Vital status and causes of death of study subjects were determined from
      January 1, 1985 to December 31, 1997 by linking cohort data with the National
      Mortality Database. Person-year accumulation began on the date of entry to the
      cohort, or January 1, 1985 (whichever came later), and ended on the closing date
      of the study (December 31, 1997), if alive; or the date of death. RESULTS: This
      retrospective cohort study examined cancer mortality among 86,868 workers at an
      electronics factory in the northern Taiwan. Using various durations of employment
      and latency and adjusting for age and calendar year, no significantly elevated
      SMR was found for any cancer in either male or female exposed workers when
      compared with the general Taiwanese population. In particular, the risk of female
      breast cancer was not found to be increased. Although ovarian cancer suggested an
      upward trend when analyzed by length of employment, ovarian cancer risk for the
      entire female cohort was not elevated. CONCLUSIONS: It is concluded that this
      study provided no evidence that exposure to chlorinated organic solvents was
      associated with human cancer risk.

PMID- 14732306
TI  - Method of detecting beta-lactam antibiotic induced vancomycin resistant MRSA
      (BIVR).
AB  - Despite the fact that the combination of vancomycin and a beta-lactam antibiotic
      are known to act synergistically on vancomycin-susceptible Staphylococcus aureus
      (VSSA), some MRSA have emerged showing antagonism to the combination of
      vancomycin and a beta-lactam antibiotic. These MRSA are called beta-lactam
      antibiotic-induced vancomycin resistant MRSA (BIVR). A method based on this
      antagonistic phenomenon has been devised to detect BIVR strains. The method
      inhibits the VSSA strain but allows the BIVR strain to grow. Forty-six
      commercially available beta-lactam antibiotics induced the vancomycin-resistance.
      Using this detection method, 717 MRSA clinical isolates obtained from eight
      institutes throughout Japan were thus screened and 6.3% of these were detected as
      BIVR when judged at 48 h.

PMID- 14732307
TI  - Preliminary susceptibility testing guidelines for AZD2563, a long-acting
      oxazolidinone.
AB  - Rapid expansion of antimicrobial resistance has led to the development of new
      antimicrobial agents. AZD2563 is a novel oxazolidinone that has activity similar
      to linezolid and the potential for extended dosing intervals. Recent Gram
      positive clinical organisms (1572 strains) were tested including four
      oxazolidinone-resistant enterococci. Strains processed were: 313 Staphylococcus
      aureus, 299 coagulase-negative staphylococci, 305 enterococci, 305 Streptococcus
      pneumoniae, 300 other streptococci (beta-haemolytic and viridans group) and 50
      other rarely isolated Gram-positive species. The methods (agar and broth
      dilution, disk diffusion) of the National Committee for Clinical Laboratory
      Standards (NCCLS; M7-A6, M2-A8) were followed and linezolid was used as a control
      agent. A tentative MIC breakpoint (<or=2mg/l) for AZD2563 was based on the
      manufacturer's recommendation, preliminary pharmacodynamic information and
      similarity to the current linezolid interpretive criteria. Correlation between
      AZD2563 MIC values and zone diameters around 30 microg AZD2563 disks indicated a
      99.9% categorical agreement and all intermethod errors were minor. Comparison of
      agar dilution to broth microdilution MIC results for AZD2563 showed 100.0%
      agreement +/- one log(2) dilution step (89.2% of MIC results were identical).
      Scattergrams suggest that all Gram-positive organisms could be accurately tested
      using the same interpretive criteria: susceptible at <or=2mg/l (>or=20 mm),
      intermediate at 4 mg/l (17-19 mm) and resistant at >or=8 mg/l (<or=16 mm). These
      tentative AZD2563 interpretive guidelines should facilitate in vitro
      susceptibility testing during clinical trials and detect all oxazolidinone
      resistant isolates.

PMID- 14732308
TI  - In vitro activity of ABT773, a new ketolide derivative exhibiting innovative
      microbiological properties against well-characterised antibiotic resistant
      pathogens in Italy.
AB  - The in vitro activity of ABT773, a new ketolide, was assessed against a
      collection (518) of well-characterised Gram-positive and Gram-negative pathogens
      and compared with that of other appropriate drugs. ABT773 was active (MIC-90=0.03
      mg/l) against the staphylococci tested which included macrolide-resistant but
      clindamycin susceptible organisms. Streptococcus pneumoniae, S. pyogenes and S.
      agalactiae were also inhibited (MIC-90 range: <0.0075-0.5mg/l) irrespective of
      their antibiotic resistance phenotype. Enterococcus faecalis was sensitive to
      ABT773 with the exception of VanA mutants. E. faecium showed poor susceptibility
      to ABT773. The activity of the new ketolide against Haemophilus influenzae and
      Moraxella catarrhalis was comparable with that of the most potent drugs tested.
      ABT773 displays the characteristics of a promising agent that deserves to be
      introduced as the empirical therapy of infections caused by the bacterial species
      tested here, even if they are multiply resistant.

PMID- 14732309
TI  - Comparison of daptomycin MIC results by DIN, NCCLS, SFM, and SRGA methods for 297
      Gram-positive organisms.
AB  - Daptomycin is a novel lipopeptide antibiotic with potent in vitro antibacterial
      activity against Gram-positive pathogens. For daptomycin minimal inhibitory
      concentration (MIC) testing, National Committee for Clinical Laboratory Standards
      (NCCLS) recommends the use of broth containing physiological levels of calcium
      (50 microg/ml). The daptomycin susceptibility of 297 organisms was determined by
      NCCLS (Mueller-Hinton (MH) broth), Deutsches Institut fur Normung (DIN; isotonic
      broth), Societe Francaise de Microbiologie (SFM; three batches MH agar), and
      Swedish Reference Group for Antibiotics (SRGA; PDM agar). All media were
      supplemented to 50 microg/ml Ca(2+). There was good correlation between DIN and
      SFM methods (for staphylococci) with NCCLS results. Enterococci MICs using SFM
      methods were one to three dilutions lower and pneumococci results were one
      dilution higher than NCCLS. SRGA results were higher than NCCLS by one to four
      dilutions. Use of isotonic agar is an accepted alternative to isosensitest agar
      for the DIN method.

PMID- 14732310
TI  - In vivo activity of amoxicillin/clavulanic acid and erythromycin in experimental
      otitis media caused by Streptococcus pneumoniae plus Haemophilus influenzae.
AB  - A gerbil model of acute otitis media induced by Streptococcus pneumoniae plus
      Haemophilus influenzae was used to assess the efficacy of amoxicillin/clavulanic
      acid (A/C) (1.5/0.3, 2.5/0.5 and 10/2 mg/kg) and erythromycin (2.5, 10, 20 and 50
      mg/kg) with or without acetaminophen. The amoxicillin/clavulanic acid MIC was
      1/0.5 mg/l for both organisms and the erythromycin MICs were 0.12 and 4 mg/l for
      S. pneumoniae and H. influenzae, respectively. The organisms were inoculated
      directly into the middle ear (ME) and antibiotic treatment started 2 h post
      inoculation and continued at 8h intervals for three doses. Acetaminophen was
      administered at 50 mg/kg. Samples for bacterial counting were obtained from the
      ME on day 2. Amoxicillin/clavulanic acid peri-MIC concentrations in ME were
      effective in eradicating both organisms. Despite the inflammation induced by S.
      pneumoniae, erythromycin did not eradicate H. influenzae at ME concentrations
      (2.4 mg/l for erythromycin 50 mg/kg) higher than those obtained in humans but
      lower than the MIC.

PMID- 14732311
TI  - Streptococcus pneumoniae in Saudi Arabia: antibiotic resistance and serotypes of
      recent clinical isolates.
AB  - During 2000, 154 clinical Streptococcus pneumoniae isolates were collected from
      or through three major hospitals serving the Western, Central, and Eastern
      regions of the Kingdom of Saudi Arabia. Ninety-one (59.1%) of the 154 isolates
      were resistant to penicillin with 23 strains (14.9%) highly resistant. Resistance
      was more prevalent among isolates obtained from patients <10 years of age and
      from isolates cultured from blood and cerebral spinal fluid. Decreased
      sensitivity to ceftriaxone, erythromycin, trimethoprim-sulphamethoxazole, and
      levofloxacin was found in 14.9, 15.6, 9.7, and 1.3% of isolates, respectively.
      There were no significant differences in the resistance pattern between isolates
      obtained from patients in the three different geographical areas. Serotypes of
      116 isolates revealed the most prevalent types to be (descending order) 4, 3,
      19F, 9V, 6A, 19A, 14 and 23F, comprising 75% of all strains typed; 9.5% of
      isolates were nontypable. S. pneumoniae isolates from Saudi Arabia have become
      more resistant to penicillin and other antimicrobials over the past 20 years.

PMID- 14732312
TI  - Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae
      isolated from children with community-acquired respiratory tract infections in
      Central Poland.
AB  - Resistance to commonly used antimicrobial agents among the key respiratory
      pathogens is increasing worldwide and therefore a rational choice of an empirical
      treatment requires knowledge of both global and local resistance patterns. The
      susceptibility of 185 Streptococcus pneumoniae and 169 Haemophilus influenzae
      isolates collected from January 1999 to May 2002 at the Children's Memorial
      Health Institute, Warsaw, Poland, from 351 children with community-acquired
      respiratory tract infections (RTIs) has been determined. Of S. pneumoniae
      isolates, 84% were susceptible to penicillin, 91% to cefaclor, 95% to cefuroxime,
      98% to cefotaxime, 79% to erythromycin, 46% to co-trimoxazole, 82% to clindamycin
      and 59% to tetracycline. The majority (83%) of erythromycin-resistant isolates
      tested carried the erm(B) gene, conferring the MLS(B) phenotype. All tetracycline
      resistant S. pneumoniae strains analysed were tet(M) positive and tet(O)
      negative. A total of 24% of H. influenzae isolates were beta-lactamase-positive.
      H. influenzae susceptibility to amoxicillin/clavulanate, cefaclor, cefuroxime,
      azithromycin, tetracycline and co-trimoxazole was 100, 89, 94, 96, 96 and 43%,
      respectively.

PMID- 14732313
TI  - PROTEKT 1999-2000: a multicentre study of the antibiotic susceptibility of
      respiratory tract pathogens in Hong Kong, Japan and South Korea.
AB  - A multicentre surveillance study performed in the Far East during 1999-2000
      investigated the in vitro activity of >20 antibacterials against common
      respiratory pathogens. In Hong Kong, Japan, and South Korea, 57.1, 44.5 and 71.5%
      Streptococcus pneumoniae were penicillin-resistant and 71.4, 77.9 and 87.6% were
      erythromycin-resistant, respectively. Overall, >90% of penicillin-resistant
      strains were also macrolide-resistant. All strains were susceptible to
      telithromycin. Fluoroquinolone-resistant isolates in Japan (1.3%), Hong Kong
      (14.3%) and South Korea (2.9%) were mostly co-resistant to penicillin, macrolides
      and tetracycline. Beta-lactamase production by Haemophilus influenzae isolates
      was 8.5% in Japan, 17.1% in Hong Kong and 64.7% in strains from South Korea. A
      single (0.27%) BLNAR isolate was obtained in Japan. There was no fluoroquinolone
      resistance. Moraxella catarrhalis was inhibited by telithromycin at <or=0.5mg/l
      and remained susceptible to macrolides, fluoroquinolones and amoxicillin
      clavulanate. Resistance to antibacterials, particularly penicillin and
      macrolides, has reached high but stable levels in the Far East and the presence
      of multiply-resistant pneumococci is well established.

PMID- 14732314
TI  - Results from the Meropenem Yearly Susceptibility Test Information Collection
      (MYSTIC) Programme: report of the 2001 data from 15 United States medical
      centres.
AB  - The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC)
      Programme is an international surveillance network of more than 100 medical
      centres where meropenem is the primary therapeutic carbapenem. Institutions have
      been monitored since 1997 (1999 in United States (US)) using National Committee
      for Clinical Laboratory Standards (NCCLS) reference susceptibility methods to
      monitor in vitro activity of meropenem and selected other broad-spectrum
      antimicrobial agents. In 2001, a total of 2874 strains were processed from the 15
      US medical centres. Molecular methods were associated with MIC methods as needed
      for defining epidemic spread of resistant strains. The meropenem MIC(90) values
      were 0.03 mg/l for Citrobacter spp., Escherichia coli and Klebsiella spp.; 0.06
      mg/l for Proteus mirabilis and Serratia spp. and 0.12 mg/l for Enterobacter spp.
      This potency was 8-16-fold greater than that of imipenem and the meropenem
      spectrum of activity versus the Enterobacteriaceae was the broadest of all tested
      antimicrobial agents. Only piperacillin/tazobactam (MIC(9), 64 mg/l) and
      tobramycin (MIC(90), 4 mg/l) were active against more than 90.0% of Pseudomonas
      aeruginosa at the NCCLS susceptible breakpoint, and the carbapenems were the most
      active compounds against Acinetobacter spp. However, Acinetobacter spp. isolates
      were resistant to all of the antimicrobial agents tested and the molecular typing
      results suggested that they were epidemiologically related. Only ciprofloxacin
      and ceftazidime had significantly reduced activity against oxacillin-susceptible
      staphylococci (87.9-92.6% susceptible. These 2001 US MYSTIC Programme results
      demonstrated no significant decline in carbapenem activity or susceptibility
      rates compared with the previously monitored years (1999-2000). Most apparent
      were the decreasing susceptibility rates for ciprofloxacin and ceftazidime
      against staphylococci. Continued surveillance in these institutions appears
      warranted as sites of high potential emerging resistance risk.

PMID- 14732315
TI  - Concentration-dependent changes in the susceptibility and killing of
      Staphylococcus aureus in an in vitro dynamic model that simulates normal and
      impaired gatifloxacin elimination.
AB  - To demonstrate the impact of normal (NEK) and impaired elimination kinetics (IEK)
      of gatifloxacin on its ability to protect from losses in the susceptibility of
      Staphylococcus aureus, a clinical isolate of methicillin-resistant S. aureus at a
      starting inoculum of 10(8)cfu/ml was exposed to 3 days of quinolone dosing. A
      series of monoexponential pharmacokinetic profiles with half-lives of 7 h (NEK)
      and 31 h (IEK) were simulated over 32- and 8-fold ranges of the 24 h area under
      the concentration-time curve (AUC(24))-to-MIC ratio, respectively. The simulated
      AUC(24)/MICs were designed to provide peak concentrations (C(max)s) close to the
      MIC, between the MIC and the mutant prevention concentration (MPC), i.e., within
      the mutant selection window (MSW), and above the MPC. With both NEK and IEK
      simulations, significant increases in MIC were observed at those AUC(24)/MICs
      that correspond to gatifloxacin concentrations within the MSW over most of the
      dosing interval (>25%). No such increases were observed at the smallest
      AUC(24)/MIC (10h with NEK and 20 h with IEK) when the simulated C(max)s were
      close to the MIC, with minimal if any bacterial killing, and at the highest
      AUC(24)/MICs (310 and 160 h, respectively) when gatifloxacin concentrations
      exceeded the MPC over most of the dosing interval, with maximal antimicrobial
      effect. These 'protective' AUC(24)/MIC ratios correspond to 135% of the usual
      gatifloxacin clinical dose (400 mg NEK) and 60% of the loading and maintenance
      doses (400 mg, then 200 mg IEK). This study predicts different protective
      potentials of gatifloxacin in IEK and NEK against staphylococcal resistance and
      supports the MSW concept.

PMID- 14732316
TI  - Failure to eradicate Group A beta-haemolytic streptococci (GABHS) from the upper
      respiratory tract after antibiotic treatment.
AB  - The clinical efficacy, safety and bacteriological eradication of Group A beta
      haemolytic streptococci (GABHS) from the throat was studied after treatment of
      streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a
      prospective, open labelled, comparative, randomised trial of 265 evaluable
      patients seen in one centre. All three antibiotics were administered in the
      recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were
      given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and
      adverse events were similar for all three antibiotics used, with a prompt
      clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate
      (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for
      penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains
      a clinically effective and safe antibiotic for the treatment of streptococcal
      pharyngitis. However, compliance and convenience for parents and children when
      they are asked to follow a 10 days course, especially when the patient has
      improved from the second or third day, together with the high incidence of
      bacteriological eradication failures, is an issue.

PMID- 14732317
TI  - Novel effect of voriconazole on conidiation of Aspergillus species.
AB  - Our previous studies of Aspergillus fumigatus showed that colonies that grew in
      the presence of voriconazole (VCZ) were characteristically white without
      pigmentation. We therefore investigated the effect of various triazoles on
      conidiation and pigmentation in four commonly isolated Aspergillus species and
      the results were compared with those obtained for polyene and echinocandin
      classes of antifungal drugs. Aspergillus cultures were grown on Sabouraud
      dextrose agar containing subinhibitory concentrations of the antifungal drugs;
      fungal colonies that grew in the presence of drug were examined microscopically
      for conidiation and the number of conidia per fungal colony was determined by
      haemocytometry. Voriconazole at 0.125-0.5 mg/l inhibited conidiation in A.
      fumigatus, Aspergillus flavus, Aspergillus niger and Aspergillus nidulans
      producing white colonies. The effect of voriconazole was concentration dependent
      and greater than 99% inhibition of conidiation was obtained in A. flavus at 0.5
      mg/l. When the white colonies were subcultured on drug-free medium, they readily
      produced conidia and pigmentation indicating that the effect is reversible. Other
      triazoles such as itraconazole (ITZ) and posaconazole (PCZ) were poor inhibitors
      of conidiation. On the other hand, ravuconazole (RCZ) with structural similarity
      to voriconazole inhibited conidiation in A. fumigatus and A. flavus, but not in
      A. niger and A. nidulans. Amphotericin B (AMB), nystatin (NYS), caspofungin (CFG)
      and micafungin (MFG) showed no effect on conidiation. Varying ability among the
      triazoles to inhibit conidiation in Aspergillus species suggests that the
      mechanism of action may be unrelated to the well-known inhibition of p450
      dependent 14alpha-sterol demethylase, and perhaps is due to direct or indirect
      effect on the formation of conidia.

PMID- 14732318
TI  - Pharmacokinetics of amphotericin B lipid complex in critically ill patients on
      continuous veno-venous haemofiltration.
AB  - Pharmacokinetics of amphotericin B lipid complex (ABLC) was determined in two
      critically ill patients requiring continuous veno-venous haemofiltration (CVVH)
      because of acute renal failure. ABLC was administered at a mean daily dose of
      4.94 mg/kg for suspected invasive mycosis. Mean C(max) was 0.56 microg/ml, the
      mean AUC(0-24 h) was 7.46 mgh/l, V(ss) 9.13 l/kg, and t(1/2) was 13.21 h. The
      haemofilter clearance accounted about 20% of the total ABLC clearance. In one
      patient sampling was repeated after CVVH had been discontinued. The concentration
      time profiles were very similar on and off haemofiltration. Data on our two
      patients suggest, that pharmacokinetics of ABLC is not significantly affected by
      CVVH and that ABLC can be administered at the standard doses during CVVH.

PMID- 14732319
TI  - The effects of rifampicin and fluoroquinolones on tubercle bacilli within human
      macrophages.
AB  - The objective of this study was to determine the activities of rifampicin,
      ciprofloxacin and sparfloxacin against M. tuberculosis H37Rv in human
      macrophages. The minimal inhibitory concentrations (MIC) were determined by agar
      macrodilution and broth microdilution methods and were 0.5, 1 and 0.125 mg/l,
      respectively. Concentrations of rifampicin at 0.5 and 2.5 microg (P<0.001),
      ciprofloxacin at 4 and 8 microg (P<0.001) and sparfloxacin at 0.125 microg
      (P<0.05), 0.625 microg (P<0.001) and 1.25 microg (P<0.001) were found to be
      effective against intracellular bacteria. Ciprofloxacin and especially
      sparfloxacin were effective in macrophages and may be useful in the treatment of
      tuberculosis particularly infections caused by multiply drug resistant strains.

PMID- 14732320
TI  - Low in vitro selection frequencies of enterococcal and staphylococcal mutants
      resistant to the oxazolidinone AZD2563.
AB  - Mutants with oxazolidinone MICs, 2- to 16-fold higher than those of parents, were
      selected from two of five clinical isolates of Enterococcus faecalis during
      exposure to AZD2563, but only at frequencies of ca. 10(-8). Resistance was not
      selected in Enterococcus faecium, Staphylococcus aureus or coagulase-negative
      staphylococci (CoNS). Mutants of one E. faecalis isolate had a G2576-->U 23S rRNA
      mutation; mutants derived from the second E. faecalis isolate lacked this
      mutation.

PMID- 14732321
TI  - In vitro effect of levofloxacin and vancomycin combination against high level
      aminoglycoside-resistant enterococci.
AB  - The in vitro effects of levofloxacin and vancomycin in combination were evaluated
      against high level aminoglycoside-resistant (HLAR) enterococci using chequerboard
      and time-kill curve techniques. We examined 28 strains of enterococci comprising
      17 Enterococcus faecalis, 10 E. faecium and one E. durans. The combination of
      vancomycin and levofloxacin had indifferent activity against all isolates
      according to chequerboard microdilution method, but was synergistic for two
      isolates, one E. faecium and one E. faecalis, using the time-kill curve method.
      Both strains were levofloxacin resistant and had high level aminoglycoside
      resistance to gentamicin and streptomycin. Antagonism was not detected in any
      strain. The results of this study suggested that the combination of vancomycin
      with levofloxacin does not often show synergistic effect against high level
      aminoglycoside-resistant enterococci.

PMID- 14732322
TI  - Genetic and phenotypic characterization of resistance to macrolides in
      Streptococcus pyogenes from Argentina.
AB  - Five hundred and seventy-eight strains of group A streptococci (GAS) isolated
      mostly from paediatric pharyngeal swabs were tested to evaluate their
      susceptibility to erythromycin. Resistant strains were then tested for their MICs
      to erythromycin and clindamycin, their phenotype of resistance to macrolides
      lincosamides-streptogramin (MLS(B)) and for the presence of macrolide resistance
      genes. The rate of resistance to erythromycin was 8.2%. Constitutive, inducible
      and M phenotypes of resistance were detected in 2.1, 2.1 and 95.8% of resistant
      strains, respectively. All M phenotypes harboured the mefA gene, whereas
      constitutive and inducible phenotypes had ermB and ermTR genes, respectively.

PMID- 14732323
TI  - Studies on the antibacterial potentiality of isoflavones.
AB  - The isoflavonoid compounds 'YS11-YS21' were screened for possible antimicrobial
      property against 12 known Gram-positive and Gram-negative sensitive bacteria.
      YS11 and YS16 failed to show antimicrobial activity and YS12, 13, 14, 15, 17, 18
      and 20 had moderate antimicrobial action. Compounds YS19 and YS21 showed
      pronounced antimicrobial property. YS19 and YS21 were then tested in vitro
      against 214 strains of bacteria from one Gram-positive and six Gram-negative
      genera. The minimum inhibitory concentration (MIC) of YS19 and YS21 was
      determined by agar dilution method and ranged from 25 to 200 mg/l in most
      strains. At concentrations of 30 and 60 microg/mouse these compounds offered
      significant protection to mice challenged with 50 median lethal dose (MLD) of a
      virulent strain of Salmonella Typhimurium.

PMID- 14732325
TI  - Dengue diagnosis, advances and challenges.
AB  - Dengue diagnosis was one of the topics discussed at the symposium 'The Global
      Threat of Dengue - Desperately Seeking Solutions' organized during the 10th
      International Congress of Infectious Diseases held in Singapore in 2002. In this
      paper, a review is presented focusing on the main advances, problems and
      challenges of dengue diagnosis.IgM capture ELISA, virus isolation in mosquito
      cell lines and live mosquitoes, dengue specific monoclonal antibodies and PCR
      have all represented major advances in dengue diagnosis. However, an appropriate
      rapid, early and accessible diagnostic method useful both for epidemiological
      surveillance and clinical diagnosis is still needed. Also, tools that suggest a
      prognosis allowing for better management are also needed. Finally, laboratory
      infrastructure, technical expertise and research capacity must be improved in
      endemic countries in order to positively influence dengue surveillance, clinical
      case management and the development of new approaches to dengue control.

PMID- 14732326
TI  - Cell density--dependent regulation: basic principles and effects on the virulence
      of Gram-positive cocci.
AB  - PRINCIPLES: Quorum sensing (QS) regulation appears to be a consequence of
      interbacterial communication by which bacteria of one or even different species
      learn about their current population density and react in a defined way to that
      information. QS-regulation is a three step process: in the first step specific
      signaling molecules are produced and secreted to the exterior space. In the
      second step, the molecules accumulate e.g. with growing population density. In
      the last step, a supra-threshold concentration of the molecules is extra- or
      intra-cellularly sensed by the bacteria and leads to a cascade of regulatory
      activities. While Gram-negative bacteria can employ five or more different
      chemical classes of signaling molecules, Gram-positive cocci predominantly use
      special oligopeptides for specific signaling. DESCRIPTIONS: Examples of QS
      regulatory effects on virulence factor expression in Staphylococcus aureus,
      Streptococcus mutans, and Enterococcus faecalis are given. In these bacteria, QS
      regulation appears to be crucial for displaying tissue invasiveness and/or
      biofilm formation. APPLICATIONS: The high specificity of the initial signal
      sensing and the importance for expressing special virulence traits make this type
      of gene expression control a promising target for the development of novel
      therapeutics. The options for such therapies are critically discussed based on
      practical experiences with interference in S. aureus QS-regulation.

PMID- 14732327
TI  - Prosthetic valve endocarditis due to Listeria monocytogenes. Report of two cases
      and reviews.
AB  - INTRODUCTION: Endocarditis due to Listeria monocytogenes is a rare but serious
      disease often leading to valve dysfunction and heart failure. Two cases of
      listerial prosthetic valve endocarditis are reviewed along with 66 cases
      previously reported. RESULTS: The mean age of patients with listerial
      endocarditis increased from 47.1 years in the decades from 1955-1984 to 65.5
      years from 1985-2000. Chronic debilitating diseases, solid tumours and
      immunosuppression associated with organ transplantation, hematologic neoplasia or
      AIDS were found in 41.1% of cases. Listerial endocarditis was a vegetative and
      destructive process, with dehiscense of the prosthesis and occasionally, abscess
      formation, fistulization and pericarditis. Treatment with penicillin or
      ampicillin alone or combined with gentamicin was adequate therapy in most cases.
      Vancomycin together with gentamicin may be a reasonable alternative therapy.
      CONCLUSIONS: Despite problems associated with microbial persistence and relapses
      in other forms of human listeriosis, antimicrobial therapy alone may be a
      successful treatment for listerial endocarditis, including cases occurring on
      prosthetic valves. Valve replacement may be reserved for complicated cases with
      valve dehiscense, cardiac failure or myocardial abscess. Overall mortality was
      35.3%, although most patients who died did so before 1985 and since then
      mortality has been significantly reduced to 12%.

PMID- 14732328
TI  - Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous
      disease: comparison of Aspergillus nidulans and Aspergillus fumigatus.
AB  - OBJECTIVE: Chronic granulomatous disease (CGD) is a rare inherited disorder of
      NADPH oxidase in which phagocytes fail to generate reactive antimicrobial
      oxidants. Invasive fungal infections are an important cause of morbidity and
      mortality in CGD patients, with Aspergillus spp. being the most frequent fungal
      pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to
      Aspergillus nidulans and compared them with those due to Aspergillus fumigatus.
      METHODS: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male
      CGD patients were found in MEDLINE. RESULTS: Fourteen cases (58%) were due to
      Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli
      were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus
      nidulans was associated with pulmonary infection and involved 'small bones' more
      frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD
      patients with Aspergillus nidulans osteomyelitis died compared with none of those
      with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans
      and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment
      combined with surgery and immunotherapy. CONCLUSION: Aspergillus nidulans causes
      osteomyelitis in CGD patients relatively frequently compared with Aspergillus
      fumigatus and may be accompanied by higher mortality. This contrasts with the low
      frequency with which Aspergillus nidulans causes osteomyelitis in patients with
      other types of immunodeficiency.

PMID- 14732329
TI  - Burden of hospitalization of patients with Candida and Aspergillus infections in
      Australia.
AB  - OBJECTIVES: This study examined the burden of hospitalization of patients with
      Aspergillus and Candida infections in Australia from 1995 to 1999. METHODS: Data
      were extracted from the National Hospital Morbidity Database. A hospitalization
      with an aspergillosis diagnosis was defined as any discharge with a diagnosis of
      aspergillosis. A hospitalization with a candidiasis diagnosis was defined as any
      discharge with a diagnosis of disseminated, invasive, or non-invasive
      candidiasis. Outcome measures included number of hospitalizations, length of stay
      (LOS), cost (AUS$), and mortality. RESULTS: 4583 hospitalizations with an
      aspergillosis diagnosis and 57,758 hospitalizations with a candidiasis diagnosis
      were identified. These hospitalizations were associated with a total of 813,398
      hospital days, AUS$563 million in cost, and 4967 in-hospital deaths during the
      study period. The mean LOS for a hospitalization with an aspergillosis diagnosis
      was 12 days, cost AUS$9,334, and was associated with 8% mortality. For
      disseminated, invasive, and non-invasive candidiasis, the respective mean LOS
      were 31, 17, and 12 days; costs were AUS$33,274, AUS$12,954, and AUS$7,694; and
      mortality was 26%, 9%, and 8%. CONCLUSIONS: Hospitalizations with diagnoses for
      fungal infections were associated with lengthy hospital stays, high costs, and
      high mortality.

PMID- 14732330
TI  - Co-existing conditions for deaths from infectious and parasitic diseases in
      Australia.
AB  - OBJECTIVE: To examine the frequency distribution of co-existing conditions for
      deaths where the underlying cause was infectious and parasitic diseases.
      MATERIALS AND METHODS: Besides the underlying cause of death, the distributions
      of co-existing conditions for deaths from infectious and parasitic diseases were
      examined in total and by various age and sex groups, at individual and chapter
      levels, using 1998 Australian mortality data. RESULTS: In addition to the
      underlying cause of death, the average number of reported co-existing conditions
      for a single infectious and parasitic death was 1.62. The most common co-existing
      conditions were respiratory failure, acute renal failure - non-specific causes,
      ischaemic heart disease, pneumonia and diabetes. When studying the distribution
      of co-existing conditions at the ICD-9 chapter level, it was found that the
      circulatory system diseases were the most important. There was an increasing
      trend in the number of reported co-existing conditions from 60 years of age
      upwards. Gender differences existed in the frequency of some reported co-existing
      conditions. The most common organism types of co-existing conditions were other
      bacterial infection and other viruses. CONCLUSIONS: The study indicated that the
      quality of death certificates is less than satisfactory for the 1998 Australian
      mortality data. The findings may be helpful in clarifying the ICD coding rules
      and the development of disease prevention strategies.

PMID- 14732331
TI  - Nosocomial enterococcal infection in neonates.

PMID- 14732332
TI  - Intrauterine parvovirus B19 infection: early prenatal diagnosis is possible.

PMID- 14732333
TI  - The first case of obstructing bronchial aspergillosis caused by Aspergillus
      sydowi.

PMID- 14732335
TI  - Protein kinase C-eta (PKC-eta) is required for the development of inducible
      nitric oxide synthase (iNOS) positive phenotype in human monocytic cells.
AB  - Several murine and human monocytic cell lines and monocyte-derived macrophages
      (MDM) from healthy volunteers were studied to compare their production of nitric
      oxide (NO) and induction of iNOS following endotoxin treatment. Although the
      human cells were sensitive to endotoxin and responded well by producing TNF-alpha
      and matrix metalloproteases (MMP), there was no induction of iNOS expression or
      NO production by any of these cells. Murine cells, however, produced large
      amounts of NO and expressed iNOS following similar endotoxin stimulation. We
      investigated the expression of PKC isotypes in all human and murine cell lines as
      well as in MDM, and found that the human cells lacked PKC-eta while the murine
      counterparts lacked PKC-beta1. Subsequently, human cells that were transfected
      with PKC-eta were found to make large quantities of NO following endotoxin
      exposure, an observation not seen in untransfected cells. We propose that PKC-eta
      is essential for the development of the iNOS positive phenotype in human
      monocytic cells, and may be responsible for the development of a number of
      inflammatory related conditions. As such it may be a suitable target for
      therapeutic intervention.

PMID- 14732336
TI  - Use of ISO-NOP200 for measurement of NO in the gas phase under controlled
      humidity conditions.
AB  - A technique has been developed to measure nitric oxide (NO) in the gas phase
      using the ISO-NOP200 NO-specific probe, which was designed to only measure NO in
      solution. It was found that probe output was responsive to the relative humidity
      (RH) of the atmosphere. Increasing sensitivity of probe output to NO was observed
      with increasing RH but the time to achieve a stable output was also increased.
      The recommended method to give high sensitivity but an acceptable time between
      analyses was to hold the probe at a constant temperature (20 degrees C) in a
      sealed 20 ml glass vial containing 4 ml of a saturated solution of NaCl, which
      provides a constant RH of 75%. NO standards and samples were injected directly
      into the vial and provided good baseline stability and a limit of detection of
      0.18 microl/L in the vial. The limit of detection of the analytical sample will
      depend on the volume of gas injected into the vial. Up to 4 ml could be injected
      without disturbing probe stability and this equates to a detection limit of 0.75
      microl/L NO. However, analysis of the internal atmosphere of banana fruit could
      only consistently extract 1 ml of gas, which gave a detection limit of 3 microl/L
      NO.

PMID- 14732337
TI  - Normalization of nitric oxide flux improves physiological parameters of porcine
      kidneys maintained on pulsatile perfusion.
AB  - Early endothelial damage and resultant reduction in the beneficial production of
      nitric oxide (NO) derived from the endothelial NO synthase (eNOS) are phenomena
      associated with the functional degradation of transplanted kidneys. In contrast,
      the inflammation characteristic of kidney preservation leads to the later,
      detrimental expression of the inducible NO synthase (iNOS). We reasoned that
      provision of low-level NO (to compensate for lack of eNOS) using the chemical NO
      donor S-nitrosoglutathione (GSNO), along with an iNOS inhibitor (N-omega
      iminoethyl-L-lysine; L-NIL), might "normalize" NO levels and therefore be
      beneficial in maintenance of flow. Non-heartbeating donor porcine kidneys were
      subjected to 30-45 min warm ischemic time and stored from 3 to 30 h, simulating
      the time required for national sharing. The kidneys were then machine preserved
      with Belzer MPS (BMP) at a set systolic pressure of 40 mmHg. Eight kidneys were
      perfused for 5h with BMP only (Group 1 control), 8 kidneys with BMP+GSNO only
      (Group 2), and 8 kidneys with BMP+GSNO+L-NIL (Group 3). Lower vascular resistance
      (VR) is a predictor of improved end-organ function. Both Group 2 and 3 kidneys
      demonstrated statistically significant reduction in VR as compared to Group 1
      kidneys, with Group 3 kidneys demonstrating a greater drop in VR than Group 2.
      Reduced oxygen saturation suggests a higher metabolic rate. Only Group 3 had
      lower oxygen saturation as compared to Group 1. Increased Ca2+ concentration in
      the perfusate is a predictor of worse end-organ function. Group 2, but not Group
      3, had a higher perfusate Ca2+ concentration than Group 1. The combination of
      suppression of harmful amounts of NO, while supplying a constant low-level amount
      of NO, may improve pulsatile kidney preservation.

PMID- 14732338
TI  - Interference with Saville's method in determination of low-molecular weight S
      nitrosothiols by ultrafiltration.
AB  - To detect low-molecular weight S-nitrosothiols in human plasma, we used a system
      combining HPLC for separation and Saville's method for colorimetric detection of
      S-nitrosothiols. The sensitivity and detection limit was 1-2 nM for both S
      nitrosocysteine and S-nitrosoglutathione. When plasma was analyzed after
      ultrafiltration (with units requiring higher g force [5000 g], irrespective to
      the material of the membrane) to eliminate high molecular substances, a signal
      corresponding to S-nitrosoglutahione was recognized. This signal behaved as real
      S-nitrosoglutathione as it was partially Hg(2+)-sensitive and gradually decayed
      with time. However, the use of pre-washed units or another ultrafiltration unit
      that required lower g force (1800 g) or direct application of plasma to the HPLC
      Saville's method system did not result in such signal. Based on these
      observations, it is important to be aware of the interference originating from
      the ultrafiltration unit and its potential effect on the precise quantification
      of low molecular weight S-nitrosothiols using Saville's method.

PMID- 14732339
TI  - Neutrophil migration in inflammation: nitric oxide inhibits rolling, adhesion and
      induces apoptosis.
AB  - There is controversy in the literature over whether nitric oxide (NO) released
      during the inflammatory process has a pro- or inhibitory effect on neutrophil
      migration. The aim of the present investigation was to clarify this situation.
      Treatment of rats with non-selective, NG-nitro-L-arginine (nitro), or selective
      inducible NO synthase (iNOS), aminoguanidine (amino) inhibitors enhanced
      neutrophil migration 6h after the administration of low, but not high, doses of
      carrageenan (Cg) or Escherichia coli endotoxin (LPS). The neutrophil migration
      induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was also enhanced by
      nitro or amino treatments. The enhancement of Cg-induced neutrophil migration by
      NOS inhibitor treatments was reversed by co-treatment with L-arginine, suggesting
      an involvement of the L-arginine/NOS pathway in the process. The administration
      of Cg in iNOS deficient (iNOS(-/-)) mice also enhanced the neutrophil migration
      compared with wild type mice. This enhancement was markedly potentiated by
      treatment of iNOS(-/-) mice with nitro. Investigating the mechanisms by which NOS
      inhibitors enhanced the neutrophil migration, it was observed that they promoted
      an increase in Cg-induced rolling and adhesion of leukocytes to endothelium and
      blocked the apoptosis of emigrated neutrophils. Similar results were observed in
      iNOS(-/-) mice, in which these mechanisms were potentiated and reverted by nitro
      and L-arginine treatments, respectively. In conclusion, these results suggest
      that during inflammation, NO released by either constitutive NOS (cNOS) or iNOS
      down-modulates the neutrophil migration. This NO effect seems to be a consequence
      of decreased rolling and adhesion of the neutrophils on endothelium and also the
      induction of apoptosis in migrated neutrophils.

PMID- 14732340
TI  - The NO signaling pathway differentially regulates KCC3a and KCC3b mRNA
      expression.
AB  - Nitric oxide (NO) donors and protein kinase G (PKG) acutely up-regulate K-Cl
      cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in vascular smooth muscle
      cells (VSMCs). Here, we report the presence, relative abundance, and regulation
      by sodium nitroprusside (SNP) of the novel KCC3a and KCC3b mRNAs, in primary
      cultures of rat VSMCs. KCC3a and KCC3b mRNAs were expressed in an approximate 3:1
      ratio, as determined by semiquantitative RT-PCR analysis. SNP as well as YC-1 and
      8-Br-cGMP, a NO-independent stimulator of soluble guanylyl cyclase (sGC) and PKG,
      respectively, increased KCC3a and KCC3b mRNA expression by 2.5-fold and 8.1-fold
      in a time-dependent manner, following a differential kinetics. Stimulation of the
      NO/sGC/PKG signaling pathway with either SNP, YC-1, or 8-Br-cGMP decreased the
      KCC3a/KCC3b ratio from 3.0+/-0.4 to 0.9+/-0.1. This is the first report on a
      differential regulation by the NO/sGC/PKG signaling pathway of a cotransporter
      and of KCC3a and KCC3b mRNA expression.

PMID- 14732341
TI  - The role of a formaldehyde dehydrogenase-glutathione pathway in protein S
      nitrosation in mammalian cells.
AB  - Intracellular sulfhydryls, both protein and non-protein, are potential targets of
      nitric oxide-related species. S-Nitrosation of proteins can occur in vivo and can
      affect their activity. Metabolic pathways that regulate protein S-nitrosation are
      therefore likely to be biologically important. We now report that formaldehyde
      dehydrogenase, an enzyme that decomposes S-nitrosoglutathione, can indirectly
      regulate the level of cellular protein S-nitrosation. Nitrogen oxide donors
      induced high levels of protein S-nitrosation in HeLa cells and lower levels in
      Mutatect fibrosarcoma cells, as determined by Saville-Griess assay and Western
      dot-blot analysis. Depletion of glutathione by treatment with buthionine
      sulfoximine markedly increased protein S-nitrosation in both cell lines.
      Glutathione depletion also increased cytokine-induced S-nitrosation in brain
      endothelial cells. Formaldehyde dehydrogenase activity was 2-fold higher in
      Mutatect than in HeLa cells. We downregulated formaldehyde dehydrogenase activity
      in Mutatect cells by stably expressing antisense RNA and short-interfering RNA.
      In these cells, both protein S-nitrosation and S-nitrosoglutathione levels were
      significantly enhanced after exposure to nitrogen oxide donors as compared to
      parental cells. Overall, a strong inverse correlation between total S
      nitrosothiols and formaldehyde dehydrogenase activity was seen. Inhibition of
      glutathione reductase, the enzyme that converts oxidized to reduced glutathione,
      by dehydroepiandrosterone similarly increased protein S-nitrosation and S
      nitrosoglutathione levels in both cell lines. Our results provide the first
      evidence that formaldehyde dehydrogenase-dependent decomposition of S
      nitrosoglutathione plays a role in protecting against nitrogen oxide-mediated
      protein S-nitrosation. We propose that formaldehyde dehydrogenase and glutathione
      reductase participate in a glutathione-dependent metabolic cycle that decreases
      protein S-nitrosation following exposure of cells to nitric oxide.

PMID- 14732342
TI  - Partial hepatectomy with or without endotoxin does not promote apoptosis in the
      rat liver.
AB  - BACKGROUND: Liver insufficiency and failure has been described following subtotal
      hepatectomy. The cause is poorly understood but may be because of attrition of
      hepatocytes through enhanced cell death pathways such as apoptosis. The trigger
      for this could be reduction beyond a critical mass of liver tissue or the
      influence of endotoxin (LPS) on cytokine activation. The experiment was designed
      to answer these questions. MATERIALS AND METHODS: Rats were subjected to either
      30% or 70% hepatectomy. Sacrifice occurred on either postoperative day 2 or 4. At
      sacrifice remnant livers were examined for apoptosis through the direct Tunel
      immunoperoxidase method (apoptotic index) and soluble histone ELISA. A second
      group of rats underwent 30% or 70% hepatectomy and were given either saline or
      endotoxin (LPS). Sacrifice occurred on postoperative day 1, 2, or 4. Liver
      samples were analyzed for apoptosis by Tunel immunoperoxidase, histone-associated
      DNA, TNF-alpha, and caspase-3. Mitotic activity and evidence of hepatocellular
      necrosis were also determined. RESULTS: By comparison to prehepatectomy values,
      rats subjected to hepatectomy alone failed to disclose any effect of resection on
      apoptotic activity. By comparison to sham operated controls there was a modest
      but significant increase in apoptotic activity at day 4 in the 30% and 70%
      hepatectomized rates by apoptotic index but not the soluble histone ELISA.
      Injection of LPS without hepatectomy produced an increase in apoptotic activity
      by apoptotic index and soluble histone ELISA methods on day 1 and 2. The addition
      of 30% or 70% hepatectomy produced a sporadic, but not sustained, increase in
      apoptotic activity which may have been because of LPS injection alone. Tissue TNF
      alpha levels increased with LPS but changed little with addition of hepatectomy.
      Mitotic activity remained essentially unchanged with or without LPS injection. No
      evidence of hepatocellular necrosis was detected with LPS and extended
      hepatectomy. CONCLUSIONS: Apoptosis does not appear to be a prominent feature in
      the posthepatectomy liver, with or without addition of LPS. Even with accelerated
      TNF-alpha production from LPS, the mitotic pathways continue to take precedent.
      Apoptosis, except for occasional sporadic bursts, is effectively suppressed. It
      is not likely that apoptosis contributes to depletion of functional hepatocytes
      and liver insufficiency.

PMID- 14732343
TI  - Evaluation of academic and community surgery clerkships at a Midwestern medical
      school.
AB  - BACKGROUND: The equivalency of surgical clerkship experience between academic and
      community sites is an issue that is assessed with difficulty. We examined the
      objective performance of 222 medical students after completion of the 8-week
      surgical clerkship. Six different consecutive semesters were analyzed. There were
      two objective examinations reviewed, the National Board of Medical Examiners'
      subject examination and the surgical subportion of the Objective Structured
      Clinical Examination (OSCE) given at the end of the third year. METHODS: Medical
      students were classified into three separate groups based on the site of their
      surgical clerkship. The medical students were in either academic (100), community
      (79), or combined (academic and community) (43) locations. Medical student
      performance on the subject examination and OSCE was examined after completion of
      the general surgical clerkship. Single-factor analysis of variance testing was
      done to compare each of the three groups with respect to subject examination test
      score, or OSCE score. Significance was defined as P < 0.05. RESULTS: The combined
      group scored highest on the subject examination (73.6%). The community group
      scored highest on the OSCE (80.7%). However, no statistical significance exists
      between the three groups with regard to subject examination (P = NS) or OSCE (P=
      NS). Subject examination scores did not correlate with OSCE scores (r = 0.095).
      Objective measurements of surgical subject examination and OSCE were not
      statistically different between academic, community, and academic and community
      surgical clerkship participants. CONCLUSIONS: No statistically significant
      differences exist between the three groups with regards to OSCE failure rates,
      but the small amount of failures may have caused Type 2 error. Surgical clinical
      skills as tested by an OSCE and surgical knowledge as tested by a subject
      examination are equally attained by an academic or community surgical clerkship.

PMID- 14732344
TI  - Tumor necrosis factor alpha disrupts tight junction assembly.
AB  - BACKGROUND: We have previously shown an increase in intestinal permeability and a
      corresponding decrease in the expression of tight junction (TJ) proteins in the
      in testines of patients with Crohn's disease (CD). Tumor necrosis factor-alpha
      (TNFalpha) has been implicated in the inflammatory process of CD and its
      suppression has therapeutic benefit. ZO-1, occludin, and the claudins are key
      proteins in the TJ. HYPOTHESIS: TNFalpha disrupts the TJ. METHODS: MDCK cells
      were incubated with TNFalpha (0-100 ng/ml) for 5 days. Qualitative evaluation of
      the TJ was done with monoclonal antibody to ZO-1 detected by an
      immunofluorescence. Duplicate cells were lysed and ZO-1, occludin, and claudin-1
      amount determined by western blot. RESULTS: Immunofluorescent staining of MDCK
      cells for ZO-1 showed TJ structural disruption with increasing amount of TNFalpha
      characterized by fragmented staining of ZO-1. There were no significant
      differences in quantitation of ZO-1 or occludin in the MDCK cells for all
      TNFalpha concentrations. There was a significant decrease in the amount of
      claudin-1 with increasing concentration of TNFalpha. CONCLUSIONS: (1) MDCK TJs
      are qualitatively disrupted by TNFalpha. (2) This disruption is not because of a
      decrease in cell number, lack of cell layer confluency, or a decrease in the
      amount of ZO-1 or occludin. (3) The amount of claudin-1 present in the cell is
      decreased with increasing amounts of TNFalpha suggesting that the lack of claudin
      1 may cause a relocation of ZO-1 away from the TJ. (4) This rearrangement may
      play a role in the increased intestinal permeability seen in CD and other
      diseases.

PMID- 14732345
TI  - Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic
      agent in a murine tumor model.
AB  - BACKGROUND: Chemoradiotherapy improves survival for some cancer patients. Methods
      of enhancing treatment response would further enhance survival rates. The effect
      of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not
      previously been examined. MATERIALS AND METHODS: C57B16 mice were inoculated with
      1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10
      treatment groups when tumor volume approached 1000 mm(3). Animals received
      combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and
      the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam
      radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel
      density, and serum VEGF were determined. RESULTS: Mean (SEM) tumor volume in the
      chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the
      chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition
      of genistein produced a significant reduction in tumor microvessel density (P =
      0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving
      chemoradiation alone. CONCLUSIONS: This study provides proof of principle that
      chemoradiation can be enhanced by the addition of an antiangiogenic agent to the
      regime and suggests that further examination of such regimes is warranted.

PMID- 14732346
TI  - Sequential delivery of maturation stimuli increases human dendritic cell IL-12
      production and enhances tumor antigen-specific immunogenicity.
AB  - BACKGROUND: Despite the increasing use of dendritic cells (DCs) in clinical
      trials, questions regarding the optimal means of DC preparation, in particular
      how to achieve optimal maturation, remain unanswered. We hypothesized that
      delivering two separate sequential maturation signals to DC in vitro, mimicking
      the process of DC maturation that occurs in vivo, would enhance the ability of
      DCs to generate antigen-specific effector T cells in an experimental in vitro
      antimelanoma model. MATERIALS AND METHODS: Human monocyte-derived DCs were
      transfected with mRNA encoding melanoma-associated antigen Mart-1 (MART) or
      influenza M1 matrix protein (M1). After mRNA transfection, DCs were left
      untreated or exposed to different maturation stimuli either added simultaneously
      or delivered sequentially 18 h after first stimulation. Phenotypic DC cell
      surface marker changes and IL-12 secretion were analyzed. Specific antigen
      presentation by DCs was measured by IFN-gamma release Elispot assay using a
      CD8(+) MART peptide-specific T cell clone. RNA-transfected and treated DCs were
      cultured with autologous naive T cells and the induction of antigen-specific
      effector T cells were assessed by IFN-gamma release Elispot assay. RESULTS: DCs
      transfected and matured had increased cell-surface expression of CD40 and
      costimulatory molecules CD80, and CD86. DCs matured and further treated by
      soluble CD40 ligand (sCD40L) had a 10- and 2-fold increase in MART antigen
      presentation compared to untreated (immature) DCs and DCs treated only with a
      first maturation signal, respectively (Elispot P = 0.02). Delivery of sequential
      maturation stimuli resulted in maximal DC IL-12 secretion compared to
      simultaneous stimuli. Last, generation of antigen-specific effector T cells more
      than doubled with the sequential addition of sCD40L to mature DC stimulators
      (Elispot P = 0.009). CONCLUSIONS: Maturation of DCs following mRNA transfection
      increases expression of cell-surface costimulatory molecules. Delivery of a
      second sequential maturation stimulus enhances antigen presentation, increases IL
      12 secretion, and augments immunogenicity as evidenced by generation of tumor
      antigen-specific effector T cells. This strategy should be considered in the
      future development of RNA-based DC vaccine strategies for the treatment of
      cancer.

PMID- 14732347
TI  - Significance of total vascular exclusion for hepatic cryotherapy: an experimental
      study.
AB  - BACKGROUND: In the liver, efficacy of cryosurgical ablation of tumors located
      near the retrohepatic vena cava is impaired by the heat-sink effect. This could
      be overcome by total vascular exclusion (TVE) of the liver. In this study, the
      effect of TVE on cryosurgical ablation of liver tissue close to the retrohepatic
      vena cava was investigated with regard to the extent of the cryolesion and
      complications arising from necrosis of the caval wall. METHODS: Of a total of 28
      pigs, 14 underwent cryotherapy with TVE compared to 14 without TVE, both
      involving the vena cava. 7 animals in each group were subjected to one freeze
      cycle and 7 in each group to two freeze cycles. Temperatures in the cryolesion
      were monitored and cryolesions were documented sonographically. Laboratory
      parameters were determined pre- and postoperatively. Follow-up was 14 days.
      Morphology, extent of the cryolesion, damage to the vena cava and complications
      were assessed after autopsy. RESULTS: With TVE, freezing rates were increased and
      cryolesions were significantly larger than without TVE. Transmural necroses of
      the vena cava with complete necrosis of the intima occurred significantly more
      frequently after TVE. Macro- and microscopically, the damage to the caval wall
      was considerably more marked after cryotherapy under TVE but in all cases the
      continuity of the vessel wall remained intact. There were no ruptures,
      thrombosis, or strictures of the vena cava. CONCLUSIONS: The combination of
      cryotherapy and TVE increases the effectiveness of cryoablation in the liver
      involving the retrohepatic vena cava without any severe vascular complications
      occurring in the pig.

PMID- 14732348
TI  - Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial
      cells.
AB  - The enteric nervous system, which regulates multiple aspects of digestive
      activity, is composed of two major cell types, neurons and glial cells. Enteric
      glia, but not enteric neurons, respond to bioactive lipids with calcium
      signaling. The sphingomyelin metabolite sphingosine-1-phosphate (S1P) caused dose
      dependent calcium (Ca(2+)) signaling using extracellular and intracellular
      Ca(2+). The signal transduction cascade was pertussis toxin-insensitive and
      involved an extracellular receptor since repetitive exposure yielded diminished
      responsiveness. Inhibition of either phospholipase C or the inositol 1,4,5
      trisphosphate receptor abolished S1P effects. RT-PCR analysis demonstrated the
      presence of S1P-coupled endothelial differentiation gene (EDG) receptor mRNAs
      (EDG-1, EDG-3, and EDG-5) within the enteric nervous system. Immunocytochemical
      analysis demonstrated strong expression of both EDG-1 and EDG-3 and weak
      expression of EDG-5 in enteric glial cells. Other sphingomyelin cycle components,
      including sphingomyelin, sphingomyelinase, and sphingosine caused Ca(2+)
      transients in enteric glia. Related lipids lysophosphatidic acid and
      sphingosylphosphorylcholine also induced Ca(2+) signaling in enteric glia,
      suggesting that multiple lipid-activated signaling mechanisms exist in these
      cells.

PMID- 14732349
TI  - A noninvasive murine model of hind limb ischemia-reperfusion injury.
AB  - BACKGROUND: This study describes a novel murine method of the Controlled Tension
      Tourniquet (CTT). The CTT applies a measured circumferential tension to hind
      limbs using a tourniquet attached to digital strain gauges, and is useful for
      investigating hind limb ischemia reperfusion (IR). MATERIALS AND METHODS: Mice
      were subjected to 1, 3, or 6 h of unilateral hind limb ischemia followed by
      either 4 or 24 h of reperfusion. Blood flow in the ischemic, reperfused, and
      contralateral limbs was monitored using a Laser Doppler Imager. Edema in the IR
      limbs was documented by changes in the wet weight to dry weight ratio.
      Myeloperoxidase and tetrazolium based mitochondrial activity assays indicated
      neutrophil infiltration and tissue viability, respectively. RESULTS: During
      reperfusion following 1, 4, or 6 h, flow stabilized at 100%, 53%, and 23% of
      baseline levels, respectively. Edema was present all in IR limbs after 4 h of
      reperfusion, but increased with the duration of ischemia. After 24 h of
      reperfusion neutrophil infiltration was equivalent in all IR limbs after all
      intervals of ischemia. After 24 h of reperfusion, tissue viability after 1 h of
      ischemia was equivalent to sham or contralateral limbs. At 3 or 6 h of ischemia
      and 24 h reperfusion decreased tissue viability to 40% of sham and contralateral
      limbs. CONCLUSIONS: The CTT provides a reproducible, noninvasive model of acute
      limb ischemia, which reflects the biochemical indices of microvascular injury,
      inflammation and flow characteristic of reperfusion injury.

PMID- 14732350
TI  - Antitumor immunity induced by dendritic cell-based vaccination is dependent on
      interferon-gamma and interleukin-12.
AB  - BACKGROUND: This study was conducted to determine whether dendritic cells (DCs)
      pulsed with a tumor cell lysate can effectively vaccinate against tumor cells and
      to establish which cytokines are necessary. MATERIALS AND METHODS: Each wild-type
      mouse received two subcutaneous immunizations (days 14 and 7) with either saline,
      tumor lysate, DCs, or tumor-lysate-pulsed DCs. Gamma-interferon (gamma-IFN),
      knock-out (KO), and interleukin-12 (IL-12) KO mice were also used in
      immunizations. A tumor challenge was given at day 0. Splenocytes were assayed for
      gamma-IFN production. RESULTS: All saline-injected mice (n = 19) and all mice
      injected with tumor lysate (n = 9) developed tumors. Six of nine mice immunized
      with DCs alone and 6/24 mice treated with lysate-pulsed DCs developed a tumor.
      Splenocytes from both the saline- and lysate-immunized groups produced
      undetectable levels of gamma-IFN, while those from mice immunized with either DCs
      or pulsed DCs produced high levels of gamma-IFN. Four of five gamma-IFN KO mice
      developed tumors after immunization with tumor-lysate-pulsed DCs. None of four IL
      12 KO mice developed a tumor after immunization with wild-type pulsed DCs and
      1/10 wild-type mice developed tumor after immunization with IL-12 KO pulsed DCs.
      Three of four IL-12 KO mice developed tumors after immunization with IL-12 KO
      pulsed DCs. CONCLUSIONS: Tumor-lysate-pulsed DCs can initiate an effective
      antitumor immune response. The presence of gamma-IFN in the host is essential for
      antitumor protection. In contrast, tumor protection is observed if IL-12 is
      present in either the host or the DCs.

PMID- 14732351
TI  - Increased MMP-9 expression and activity by aortic smooth muscle cells after
      nitric oxide synthase inhibition is associated with increased nuclear factor
      kappaB and activator protein-1 activity.
AB  - OBJECTIVE: To determine the mechanism underlying increased expression and
      activity of matrix metalloproteinase 9 (MMP-9) by rat aortic smooth muscle cells
      (RA-SMC) after inhibition of inducible nitric oxide synthase (iNOS). METHODS AND
      RESULTS: Treatment of interleukin-1beta-stimulated RA-SMC with aminoguanidine led
      to an increase of 96% in MMP-9 activity (P = 0.003) by gelatin zymography, a 40%
      increase in pro-MMP-9 protein (P = 0.018) by Western blot, and a 155% increase in
      MMP-9 mRNA (P = 0.06) by reverse transcription polymerase chain reaction.
      Aminoguanidine also caused a 26% decrease in cytosolic IkappaB levels (P = 0.014)
      by Western blot, as well as a 97% increase in nuclear factor-kappaB binding and a
      216% increase in activator protein-1 binding as measured by electrophoretic
      mobility shift assay. No significant changes were noted in MMP-2 or TIMP-1
      expression, protein levels, or activity after aminoguanidine administration.
      CONCLUSIONS: MMP-9 expression and activity is increased in cytokine stimulated RA
      SMCs after iNOS inhibition, coincident with activation of the nuclear factor
      kappaB and activator protein-1 pathways. We speculate that local derangements in
      iNOS may favor MMP-9-dependent vessel wall damage in vivo via an inflammatory
      cascade mechanism.

PMID- 14732352
TI  - Protective effects of a potent C5a receptor antagonist on experimental acute limb
      ischemia-reperfusion in rats.
AB  - OBJECTIVES: The capacity of a potent C5a receptor antagonist to inhibit various
      parameters of local and remote organ injury following lower limb ischemia
      reperfusion (I/R) in rats was investigated. METHODS: Rats were subjected to 2 h
      bilateral hindlimb ischemia and 4 h reperfusion. Drug-treated rats received AcF
      [OPdChaWR] (1 mg/kg) iv either 10 min before ischemia or 10 min prior to
      reperfusion, or orally (10 mg/kg) 30 min prior to ischemia. Levels of circulating
      creatine kinase (CK), lactate dehydrogenase (LDH), alanine and aspartate
      aminotransferase (ALT/AST), creatinine, blood urea nitrogen (BUN),
      polymorphonuclear leukocytes (PMNs), and calcium (Ca(++)) and potassium (K(+))
      ions were determined. Other parameters measured included urinary protein levels,
      muscle edema, and myeloperoxidase (MPO) concentrations in the lung, liver, and
      muscle along with liver homogenate tumor necrosis factor-alpha (TNF-alpha)
      concentrations.L RESULTS: imb I/R injury was characterized by significant
      elevations of CK, LDH, ALT, AST, creatinine, BUN, proteinuria, PMNs, serum K(+),
      muscle edema, organ MPO, and liver homogenate TNF-alpha concentrations, but a
      significant reduction in serum Ca(2+) concentrations. When rats were treated with
      AcF-[OPdChaWR], there were significant improvements in all these parameters.
      CONCLUSIONS: These results indicate a pivotal role for C5a in inducing local and
      remote organ injury and suggest a possible new drug therapeutic category for
      preventing anticipated tissue injury associated with I/R.

PMID- 14732354
TI  - TLK1B is elevated with eIF4E overexpression in breast cancer.
AB  - INTRODUCTION: The overexpression of eukaryotic initiation factor 4E (eIF4E), a
      critical component of the "RNA helicase" necessary for the initiation of protein
      synthesis of mRNAs with long 5' prime untranslated regions (5'UTRs), can result
      in malignant transformation. In a prospective study on breast cancer outcome of
      women with stage I to III disease, eIF4E overexpression was an independent
      predictor of cancer recurrence (RR = 7.3, CI = 1.58-33.9). Dysregulation of
      Tousled-like kinase 1B (TLK1B), a threonine kinase with a highly conserved gene
      sequence, has been linked to defects in cell division and DNA replication. In
      cell lines, TLK1B overexpression has been recently associated with resistance to
      radiation. The 5'UTR of TLK1B is long (1088 nt) and the structure is complex. Our
      hypothesis is that TLK1B elevation is correlated with the overexpression of eIF4E
      in human breast carcinoma. MATERIAL AND METHODS: Eighty-seven patients with
      invasive breast cancer and 11 patients with benign breast disease were accrued
      prospectively. Clinical data collected include age, race, stage, grade of tumor,
      ER, and PR status. TLK1B and eIF4E levels were quantified by Western blot
      analysis. Statistical analysis was performed using Spearman correlation, paired
      and unpaired t test, and multivariate analysis. RESULTS: In the 87 cancer
      specimens from patients with breast carcinoma, eIF4E level was elevated by a mean
      of 9.5-fold (range = 1.8-48.4), and TLK1B was elevated by a mean of 9.4-fold
      (range = 1.0-58.0) when compared to the 11 specimens from noncancer patients.
      Multivariate analysis performed demonstrates the degree of eIF4E overexpression
      is independent of age, race, tumor grade, and ER or PR status of the tumor.
      Similarly, the degree of TLK1B elevation is independent of age, tumor grade, and
      ER or PR status of the tumor. Using the Spearman correlation, the degree of TLK1B
      elevation was strongly correlated with the degree of eIF4E overexpression (r =
      0.39, P = 0.001). CONCLUSIONS: Both eIF4E and TLK1B are elevated in breast cancer
      specimens but not in benign breast specimens from noncancer patients. The degree
      of TLK1B elevation is correlated with the degree of IF4E overexpression. Both
      eIF4E and TLK1B overexpression are independent of tumor grade, tumor stage, and
      ER and PR status.

PMID- 14732353
TI  - Left ventricular remodeling after experimental myocardial cryoinjury in rats.
AB  - The standard coronary ligation, the most studied model of experimental myocardial
      infarction in rats, is limited by high mortality and produces unpredictable areas
      of necrosis. To standardize the location and size of the infarct and to elucidate
      the mechanisms of myocardial remodeling and its progression to heart failure, we
      studied the functional, structural, and ultrastructural changes of myocardial
      infarction produced by experimental myocardial cryoinjury. The cryoinjury was
      successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was
      documented on echocardiograms, with an average size of about 21%. Macroscopic
      examination reflected closely the stamp of the instrument used, without
      transition zones to viable myocardium. Histological examination, during the acute
      setting, revealed an extensive area of coagulation necrosis and hemorrhage in the
      subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas
      the reparative phase started within the first week, with proliferation of
      fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of
      collagen fibers was reported with a reparative scar completed at the 30th day.
      Ultrastructural study revealed vascular capillary damage and irreversible
      alterations of the myocytes in the acute setting and confirmed the histological
      findings of the later phases. The damage was associated with a progressive left
      ventricular (LV) remodeling, including thinning of the infarcted area,
      hypertrophy of the noninfarcted myocardium, and significant LV dilation. This
      process started from the 60th day and progressed over the subsequent 120 days
      period; at 180 days, a significant increase in LV filling pressure, indicative of
      heart failure, was found. In conclusion, myocardial cryodamage, although
      different in respect to ischemic damage, causes a standardized injury reproducing
      the cellular patterns of coagulation necrosis, early microvascular reperfusion,
      hemorrhage, inflammation, reparation, and scarring observed in myocardial
      infarction with a late evolution toward heart failure. This model is therefore
      suitable to study myocardial repair after injury.

PMID- 14732355
TI  - Reduction of infarct size and preservation of endothelial function by multidose
      intravenous adenosine during extended reperfusion.
AB  - It has been proposed that infarct extension is developed from the early to the
      late phase of reperfusion (R). This study compares the protective effect of
      single or multidose administration of adenosine (Ado) on infarct size during
      early and late phases of R by attenuating neutrophil (PMN) recruitment. Forty-one
      dogs underwent 60-min left anterior descending artery (LAD) ischemia followed by
      6, 24, and 48 h of R, respectively. Infarct size (%) increased over 6 to 24 h (27
      +/- 2 to 38 +/- 4; P < 0.05 24 h versus 6 h group), with a corresponding increase
      in creatine kinase activity. Transmural myocardial blood flow (mL/min/g)
      decreased from 6 to 24 h (0.47 +/- 0.02 to 0.29 +/- 0.02; P < 0.05 24 h versus 6
      h group). PMN localization (mm(2) myocardium) in the perinecrotic tissue detected
      by immunohistochemistry with anti-CD18 antibody, and accumulation detected by
      myeloperoxidase (MPO, DeltaAbs/min/g) increased from 6 to 24 h (292 +/- 25 to 605
      +/- 44; P < 0.05 24 h versus 6 h group; and 55 +/- 7 to 96 +/- 5; P < 0.05 24 h
      versus 6 h group), respectively. In in vitro analysis, PMN adherence (mm(2)
      endothelium) to postischemic LAD increased from 98 +/- 2 to 125 +/- 3 (P < 0.05
      24 h versus 6 h group) and maximal LAD endothelium-dependent relaxation (%)
      impaired from 6 to 24 h (74 +/- 7 to 42 +/- 10; P < 0.05 24 h versus 6 h group).
      Intravenous Ado (140 microg/kg/min) for 2 h at R reduced infarct size (17 +/- 2;
      P < 0.05 Ado versus 6 h group), CD18 positive cells (130 +/- 10; P < 0.05 Ado
      versus 6 h group), MPO (14 +/- 3; P < 0.05 Ado versus 6 h group), PMN adherence
      (57 +/- 2; P < 0.05 Ado versus 6 h group), and augmented LAD vascular relaxation
      (102 +/- 5 versus 74 +/- 7; P < 0.05 Ado versus 6 h group). However, this
      protection by Ado was lost when R was extended to 24 h. Treatment with multiple
      infusion of Ado at 2, 6, 12, and 18 h R significantly preserved protective
      effects seen at 6 h R in the Ado group. Protection by multidose Ado was still
      preserved when R was extended to an additional 24 h. These data suggest that
      interventions aiming at permanently reducing R injury may thus need to be
      administered not only at early R, but also during late phase. A slow wave of PMN
      accumulation at late R may be involved in the extension of infarction and
      endothelial dysfunction.

PMID- 14732356
TI  - Simvastatin suppresses LPS-induced Akt phosphorylation in the human monocyte cell
      line THP-1.
AB  - BACKGROUND: Activation of the small GTPase, Rac, requires post-translational
      modification by isoprenylation. Statins interfere with this process by blocking
      the synthesis of isoprenoid intermediates. The protein kinase Akt is a
      multifunctional regulator of cell behavior that has been linked to Rac
      activation. We have shown that lipopolysaccharide (LPS) stimulation leads to Rac
      activation in THP-1 cells. Therefore, we hypothesized that LPS stimulation would
      also activate Akt, a downstream effector of Rac, and that this may be blocked by
      statin pretreatment. MATERIALS AND METHODS: THP-1 cells were maintained in 1%
      fetal calf serum with or without 20 microM simvastatin for 24 h, followed by LPS
      stimulation for increasing time. Cytoskeletal changes were observed using Alexa
      Phalloidin. Akt was immunoprecipitated from total cell lysate. Activated Akt was
      detected by immunoblotting with a phospho-Akt antibody and was quantified by
      image densitometry. RESULTS: LPS stimulation of THP-1 cells results in membrane
      ruffling and cell polarization. Furthermore, LPS increased Akt activation in THP
      1 cells when compared with the nonstimulated controls. Akt phosphorylation peaked
      after 15 min of LPS stimulation and was suppressed by pretreatment with
      simvastatin. CONCLUSIONS: These data demonstrate that LPS stimulation leads to
      increased Akt phosphorylation, which can be suppressed with simvastatin
      pretreatment. This suggests one possible mechanism through which simvastatin
      could modulate LPS-induced signaling events in monocytes to improve the host
      response to Gram-negative infections.

PMID- 14732357
TI  - The lack of a systemic inflammatory response syndrome supports the safety of
      pancreatic electrolysis: experimental studies.
AB  - BACKGROUND: Per-ductal pancreatic electrolysis is a new minimally invasive
      ablation treatment. Possible applications include tumor debulking and treatment
      of chronic pancreatitis. Both solid organ ablation and pancreatitis are
      associated with the risk of an overwhelming systemic inflammatory response
      syndrome (SIRS) and multiorgan failure. TNF-alpha and IL1-beta are important
      cytokine mediators of this response. The aim of this study was to measure the
      circulating levels of IL1-beta and TNF-alpha following pancreatic electrolytic
      ablation as a marker of the risk of SIRS complicating per-ductal pancreatic
      electrolysis. METHODS: Serum TNF-alpha and IL1-beta were measured in six
      treatment and six control pigs before and after laparotomy and pancreatic
      electrolytic ablation via a per-ductal approach. RESULTS: There was no
      significant rise in serum TNF-alpha and IL1-beta in association with per-ductal
      pancreatic electrolysis. CONCLUSIONS: This study supports the evidence that per
      ductal electrolysis is a safe procedure with potential for palliative treatment
      of pancreatic cancers.

PMID- 14732358
TI  - A new rabbit model of myocardial infarction without endotracheal intubation.
AB  - INTRODUCTION: When establishing a myocardial infarction model in rabbits,
      artificial ventilation under endotracheal intubation is required to prevent
      pulmonary collapse caused by pneumothorax. However, it is difficult to carry out
      endotracheal intubation due to the rabbit anatomy. We therefore attempted to
      develop a myocardial infarction model in rabbits without endotracheal intubation.
      MATERIALS AND METHODS: A facial oxygen mask with a flow rate of 200 mL/min was
      placed on anesthetized rabbits (n = 17). The sternum was carefully incised along
      the midline to avoid injury to the parietal pleura. The major branch of the left
      coronary artery was then ligated and the surgical wound was closed. To
      investigate the effects of the surgical procedure on physiological parameters,
      blood pressure and blood gas were measured during the same procedure using 10
      other rabbits. RESULTS: During the surgery, PaO(2) and PaCO(2) were stable at
      approximately 230 and 50 mm Hg, respectively. In addition, the animals did not
      experience severe ventilatory impairment. Four weeks after the myocardial
      ischemia, the overall mortality rate was 29.4% (5/17). All of the surviving
      animals showed Q-waves on ECG and myocardial infarction upon histological
      examination. CONCLUSIONS: Our new method established a chronic rabbit model of
      myocardial infarction without the need for endotracheal intubation.

PMID- 14732359
TI  - The antitumor effects of interferon-alpha are maintained in mice challenged with
      a STAT1-deficient murine melanoma cell line.
AB  - INTRODUCTION: Interferon-alpha (IFN-alpha) is currently administered to patients
      with metastatic malignant melanoma and those who are at risk for recurrence
      following surgery for high-risk lesions. Signal transducer and activator of
      transcription 1 (STAT1) is a transcription factor that is activated by IFN-alpha
      and is thought to mediate the majority of its antitumor effects. Loss of STAT1
      has been found in IFN-resistant melanoma cells. We developed a murine melanoma
      cell line in a STAT1-deficient mouse. We also transfected B16 melanoma cells with
      a wild-type form of STAT1 to induce its overexpression. Using the resulting cell
      lines and STAT1-deficient mice, we tested whether IFN-alpha could exert an
      antitumor effect on melanoma cells in the absence of STAT1-mediated signal
      transduction. MATERIALS AND METHODS: A melanoma tumor was induced in STAT1
      deficient mice via the application of DMBA (tumor initiator) followed by croton
      oil (tumor promoter). Immunohistochemical analysis confirmed that the resulting
      tumor was a malignant melanoma. Immunoblot analysis, intracellular flow
      cytometry, and gel-shift analysis were used to confirm the lack of STAT1 in the
      derivative cell line (AGS-1). In addition, the STAT1 protein was overexpressed in
      B16 melanoma cells by stable transfection with a plasmid construct encoding wild
      type STAT1. The effects of IFN-alpha on these cell lines were studied in vitro
      and in vivo. RESULTS: STAT1 was not expressed in the AGS-1 murine melanoma cell
      line. Treatment with IFN-alpha did not lead to activation of STAT1. Cell
      proliferation assays revealed that while IFN-alpha did not exert an
      antiproliferative effect on this cell line, it was capable of prolonging the
      survival of STAT1-competent C57BL/6 mice bearing 1 x 10(6) AGS-1 tumor cells in
      the intraperitoneal position (n = 20, P < 0.05), as compared to PBS-treated
      controls. Also, the survival of IFN-alpha-treated mice (as compared to PBS
      treated controls) was not affected by the overexpression of STAT1 in B16 tumor
      cells. CONCLUSIONS: This data suggests that IFN-alpha can enhance survival in an
      animal model where STAT1-mediated signal transduction and gene regulation is
      absent within the tumor but is present within the host. This data also indicates
      that the overexpression of STAT1 within the tumor does not significantly enhance
      the effects of exogenously administered IFN-alpha in this model. These findings
      indicate that the bulk of the antitumor actions of IFN-alpha may be derived from
      its effects on host tissues.

PMID- 14732360
TI  - Cytokine induction by the P. aeruginosa quorum sensing system during thermal
      injury.
AB  - INTRODUCTION: Pseudomonas aeruginosa causes serious infections in severely burned
      patients due to its ability to produce numerous virulence factors. The production
      of most of these factors is controlled by the cell-to-cell communication system
      called quorum sensing (QS). We have recently shown that several proinflammatory
      and hematopoietic cytokines are produced during infection of the burn wound with
      P. aeruginosa strain PAO1. Most of these cytokines were not produced during
      either thermal injury or P. aeruginosa infection alone. MATERIALS AND METHODS AND
      RESULTS: In this study, we tried to determine if the QS systems play a role in
      the production of cytokines during P. aeruginosa infection of burn wounds. This
      was accomplished using the murine model of thermal injury, the P. aeruginosa
      strain PAO1 and its QS defective mutant (PAO-JP2), and the Multi-probe RNase
      protection assay. The mRNA for TNF-alpha, IL-6, TGF-beta, and G-CSF was detected
      within the skin of PAO1 infected/thermally injured mice. In contrast, the
      expression of these cytokines was not detected in PAO-JP2 infected/thermally
      injured mice. In comparison with the parent strain, PAO-JP2 was not defective
      either in its growth or in its spread within the thermally injured skin. A
      complementation experiment, using a plasmid that carries the intact QS gene, was
      conducted to confirm these results. In the presence of the complementing plasmid,
      PAO-JP2 produced the mRNA for the above cytokines. CONCLUSIONS: These results
      suggest that: 1) the QS system is involved in the induction of cytokine
      expression during P. aeruginosa infection of burn wounds; and 2) this effect may
      be caused by either a component of the QS system or a QS-controlled virulence
      factor.

PMID- 14732361
TI  - Superior mesenteric artery occlusion models shock-induced gut ischemia
      reperfusion.
AB  - INTRODUCTION: Superior mesenteric artery occlusion (SMAO) is a simple and
      reproducible model of shock-induced gut ischemia/reperfusion, but some argue that
      it is not clinically relevant. The purpose of the current study was to compare
      SMAO to a standard model of controlled hemorrhage (CH) and uncontrolled
      hemorrhage (UH). METHODS: Rats had femoral lines and a jejunal mucosal laser
      Doppler placed followed by SMAO (60 min of ischemia, no resuscitation),
      controlled hemorrhage (40 mm Hg for 60 min, 2:1 resuscitation shed blood and
      lactated Ringers), or uncontrolled hemorrhage (liver injury, 3:1 resuscitation
      with lactated Ringers). Base deficit, lactate, and jejunal mucosal flow (as a
      percentage of baseline) were recorded during ischemia and for 120 min after
      reperfusion. Jejunal tissue was harvested for morphological evaluation.
      Comparison among groups was by analysis of variance (ANOVA), and significance was
      set at P < 0.05. RESULTS: Mucosal blood flow was similar among groups at the
      onset of reperfusion (CH, 16.9 +/- 5.0% versus UH, 10.9 +/- 3.1% versus SMAO,
      13.9 +/- 6.2%) and during the initial period of reperfusion. By 120 min, however,
      flow in CH (75.4 +/- 2.5%) was significantly higher that in either UH (36.4 +/-
      13.1%) or SMAO (31.7 +/- 8.4%). Histological injury was less with CH, while base
      deficit was significantly higher in CH at the onset of reperfusion (-24 +/- 2
      versus UH, -10 +/- 3 and SMAO, -6 +/- 3 mM/L) but comparable by the end (CH, -17
      +/- 4 versus UH, -16 +/- 3 and SMAO, -17 +/- 2 mM/L). CONCLUSIONS: SMAO is a
      clinically relevant model of shock-induced gut ischemia/reperfusion.

PMID- 14732362
TI  - Endotoxin releases a precursor to vasodilation from large veins in an NF-kappaB
      dependent manner.
AB  - INTRODUCTION: Our previous studies have shown that when a segment of rat aorta
      was placed upstream and in series to a rat cremasteric isolated arteriole,
      endotoxin (ET) exposure produced significant vasodilatation. Without the aorta,
      no loss of tone was noted, indicating that a precursor, as of yet unidentified,
      was washed downstream, thereby inducing vasodilation. Prior treatment of the
      donor of either the aorta or the arteriole with pyrrolidine dithiocarbamate
      (PDTC), a potent NF-kappaB inhibitor, prevented the loss of tone. This suggests a
      role for NF-kappaB in the signaling pathway. The aim of this study was to
      determine if a large vein was also capable of releasing a similar factor in
      response to ET. MATERIALS AND METHODS: This project followed the same
      experimental design except that the upstream aortic segment was replaced by a
      segment of vena cava. Male Sprague-Dawley rats were given an intraperitoneal (ip)
      injection of PDTC (100 mg/kg) or a sham injection of saline. First-order
      cremasteric arterioles were isolated, cannulated, and pressurized. A segment of
      inferior vena cava was then placed in series with the microvascular preparation.
      Arterioles were allowed to equilibrate and achieve spontaneous myogenic tone in a
      bath of warm physiological buffer over 1 h (t = 0). Internal vessel diameters
      were measured with video calipers and the response to ET or continued infusion of
      buffer was measured over 2 h (t = 120). The control group (n = 8) received a sham
      injection and the vessels were exposed to buffer only. The ET group (n = 7) was
      exposed to ET only. The PDTC group (n = 5) received PDTC only. The PDTC/ET group
      (n = 6) received PDTC and was exposed to ET. RESULTS: After equilibration,
      spontaneous tone (measured as a percentage of maximal diameter) was similar in
      the four groups (t = 0). After 2 h (t = 120), the ET group had significantly less
      tone (30.1 +/- 3.6%; P < 0.05) than the control (44.8 +/- 2.6%), the PDTC group
      (43.0 +/- 1.3%), and the PDTC/ET group (49.4 +/- 3.0%). CONCLUSIONS: These
      results show that the vena cava is capable of releasing a factor leading to
      vasodilation in response to ET in a manner similar to the aorta. Produced by the
      veins, it will affect venous capacitance as well as contribute to the total
      amount in the plasma pool affecting the tone of the resistant arterioles. Thus,
      it appears that these large conducting vessels, regardless of origin, play a role
      in the deleterious effects during septic events.

PMID- 14732363
TI  - Potential role for antiangiogenic proteins in the myocardial infarction repair
      process.
AB  - OBJECTIVE: Although angiogenic proteins have been identified as positive
      modulators of myocardial revascularization following acute myocardial infarction,
      little if anything is known regarding the role that antiangiogenic proteins have
      in myocardial revascularization. We explored the temporospatial distribution of
      endothelial-monocyte activating polypeptide (EMAP) II to determine whether
      antiangiogenic proteins have a role in the repair of myocardial tissue following
      infarction. METHODS: A rat model of myocardial infarction was utilized to examine
      EMAP II distribution (in situ hybridization) and protein expression (Western
      analysis) over a 6-week period. RESULTS: At baseline, EMAP II protein and mRNA
      are minimally expressed with transcription products localizing predominately to
      the perivascular stroma region in the normal rat myocardium. Six hours following
      myocardial infarction, EMAP II changes its distribution from the perivascular
      stroma to an invading inflammatory cell population. This is associated with a 2
      fold (P < 0.0009) increase in EMAP II protein and its transcription primarily
      localized to the infarct region. EMAP II protein expression remains elevated
      throughout the weeks following the infarction with transcription limited to the
      infarct region and a notable decrease in EMAP II transcription products noted in
      the viable vasculature surrounding the infarct zone. Six weeks following
      myocardial infarction, EMAP II protein is elevated above control, changes its
      location of transcription from the inflammatory cell population to that of the
      fibroblasts located in the relative avascular scar tissue, and has resumed its
      perivascular stromal distribution in the viable periinfarct tissue. CONCLUSIONS:
      Thus, the temporospatial distribution of this antiangiogenic protein suggests
      that negative vascular modulators may have a function in the revascularization
      process following acute myocardial infarction.

PMID- 14732364
TI  - Raised plasma endostatin levels correlate inversely with breast cancer
      angiogenesis.
AB  - BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to
      grow. The effect of surgical removal of breast tumors on plasma endostatin and
      vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues
      were analyzed for expression of Intratumoral microvessel density (IMVD) and
      endostatin. The effect of VEGF and endostatin in inducing apoptosis on human
      liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND
      METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast
      cancer patients were assayed for endostatin and VEGF via immunoassay, pre
      operatively and four weeks post-operatively. Expression of endostatin in tumor
      tissue was determined by Western blotting. IMVD was assessed following
      immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin
      levels, in breast cancer patients, were significantly elevated (P = 0.015) in the
      post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group
      (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76
      etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was
      decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with
      low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor
      VEGF levels correlated with routine clinico-pathological parameters. Endostatin
      induced endothelial cell apoptosis and modulated the cytoprotective effect of
      VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in
      patients following surgical removal of the primary tumor. The decreased IMVD seen
      in patients with higher endostatin levels may be due to the apoptosis-inducing
      effect of endostatin on microvascular endothelial cells.

PMID- 14732366
TI  - Subtotal hepatectomy: a porcine model for the study of liver regeneration.
AB  - BACKGROUND: This study aimed to devise a simple, reproducible method of subtotal
      hepatectomy in a large animal model. Such an experimental model could be useful
      in the investigation of liver regeneration and liver insufficiency after partial
      hepatectomy. Equally, this technique could be used for assessing the effect of
      artificial liver support systems on both liver function and regeneration.
      MATERIALS AND METHODS: Twenty pigs were subjected to either 70-80% liver
      resection (n = 11), or 85-90% liver resection (n = 9), using a simplified
      technique. RESULTS: Most tolerated the procedure well and showed restoration of
      full liver volume within 3 weeks. Three animals in the 90% resection group died
      with significantly raised levels of International Normalized Ratio (INR) and
      ammonia. CONCLUSIONS: These two techniques have been shown to be easily
      reproducible and well tolerated by the animals and allow easy assessment of liver
      function and regeneration in the postoperative period. The deaths in the 90%
      resection group supports the hypothesis that 90% partial hepatectomy represents a
      model of critical residual liver parenchyma.

PMID- 14732365
TI  - A novel murine model of cyclical cutaneous ischemia-reperfusion injury.
AB  - BACKGROUND: Increasing evidence points to a principal role of ischemia
      reperfusion in the pathogenesis of chronic skin ulceration, including pressure
      sores, diabetic ulcers, and venous ulcers. An incomplete understanding of this
      process and the limitations of current animal models of chronic wounds mandate a
      reproducible model in mice, in which transgenic and knockout technology are
      continually evolving. MATERIALS AND METHODS: A murine model of chronic skin
      ulceration based on cyclical magnetic compression is presented. Forty-three
      C57BL/6J mice underwent varying degrees of cyclical compression with defined
      periods of reperfusion. Injury was measured grossly as regional necrosis, and
      tissue was harvested for histology, DNA electrophoresis, and reverse
      transcription polymerase chain reaction. RESULTS: Skin necrosis became apparent
      only 12 h post cycling, and was cycle-responsive and quantitative in cycled
      subjects. Histopathologic analysis revealed a statistically significant doubling
      of the leukocyte count in sections from compressed skin versus sham controls.
      Moreover, apoptotic DNA laddering was evident in post ischemic skin and absent in
      controls. Real-time PCR analysis revealed a 300-fold higher expression in iNOS
      mRNA from cyclically compressed skin compared with normal skin: such expression
      was temporal in nature. CONCLUSIONS: A murine model of pressure necrosis, which
      bears all of the gross, histological, and molecular features of ischemia
      reperfusion injury, has been established. Application of this model to the vast
      number of transgenic mice available will further our understanding of the
      mechanism of pressure sore development.

PMID- 14732367
TI  - Genetics and Parkinson's disease.
AB  - Idiopathic Parkinson's disease is a neurodegenerative disorder that affects 1-2%
      of the population over the age of 65 years. Its aetiology is most likely a
      combination of complex genetic and environmental factors. Although Mendelian
      inheritance is seen in less than 5% of cases, recent studies have identified
      three genes mutations causing Parkinson's disease with a Mendelian inheritance
      pattern: autosomal dominantly inherited mutations of the alpha-synuclein gene on
      chromosome 4q21-q23, autosomal recessively inherited mutations of the parkin gene
      on chromosome 6q25.2-q27 and an autosomal dominantly inherited mutation of the
      Ubiquitin C-terminal hydrolase L1 (UCH-L1) gene on chromosome 4p14-15.1. A number
      of other candidate gene polymorphisms including cytochrome P450 2D6, N
      acetyltransferase 2, monoamine oxidase-B and glutathione-s-transferase M1 are
      implicated in sporadic and familial cases and may also play a minor role in the
      aetiology of Parkinson's disease.

PMID- 14732368
TI  - Pediatric traumatic brain injuries in Taiwan: an 8-year study.
AB  - Background. This study is intended to determine the causes of pediatric traumatic
      brain injuries (PTBI) in children aged 14 years or less, and to identify various
      types of craniocerebral damage resulting from different mechanisms of
      injury.Methods. From July 1, 1993 to June 30, 2001, a survey on PTBI was
      conducted in Taiwan. The data of patients used in this study were collected from
      56 major hospitals among the age group of 0-14 years. The items in the traumatic
      brain injury survey included sex, age, causes of injuries, severity, and the
      eventual outcome.Results. A total of 5349 cases were identified. The male-to
      female ratio was 1.69: 1. The incidence rate was higher in the age groups of 4-9
      years and 10-14 years. The main cause of PTBI was traffic injury, which accounted
      for 2537 of the cases (47.3%), followed by falls, 2160 (40.3%). Of all traffic
      injuries, motorcycle-related injury had the highest incidence, followed by the
      pedestrian and bicycle-related injury. This study also showed that 83.2% of the
      patients had mild injury, 9.8% had moderate injury, and 7.0%, severe
      injury.Conclusions. The results of this study suggest that it is important to
      decrease all the risk factors in the environment of homes and public areas as
      much as possible. Helmet wearing and the development of public transportation are
      essential for the prevention of head injury.

PMID- 14732369
TI  - Surgical management of spinal epidural abscess: selection of approach based on
      MRI appearance.
AB  - Spinal epidural abscess (SEA) is associated with considerable morbidity and
      mortality despite its infrequent occurrence. The evolution of magnetic resonance
      imaging has allowed for easier diagnosis of this potentially devastating
      condition. It is also possible to predict the intraoperative appearance of each
      individual case of SEA prior to the procedure, based on the MR findings. Surgical
      treatment of SEA usually involves extensive decompressive laminectomy,
      predisposing the patient to the development of spinal instability and deformity.
      Recent advances in surgical approach to SEA have seen the institution of less
      invasive techniques to manage this condition, including washout of the epidural
      space with catheters introduced via laminotomy. Our three cases illustrate the
      ability to predict the intraoperative findings in patients with SEA, and
      accordingly adjust the surgical approach to minimize the extensiveness of
      potentially destabilizing procedures, without impinging on the effectiveness of
      treatment.

PMID- 14732370
TI  - 'Out of pocket' costs to stroke patients during the first year after stroke -
      results from the North East Melbourne Stroke Incidence Study.
AB  - Non-reimbursed 'out of pocket' costs to stroke patients have not been included in
      existing cost of illness studies. We aimed to determine the nature and magnitude
      of 'out of pocket' costs to stroke patients during the first year after stroke.
      'Out of pocket' costs during the first year after stroke were documented for 165
      persons registered in a community-based stroke incidence study during 1996/1997.
      Virtually all cases reported some 'out of pocket' costs. The average cost over 12
      months was A$1110. The highest cost items were home modifications, aids and
      equipment. The most commonly incurred expense was for prescription medications.
      Total 'out of pocket' costs incurred by first-ever stroke patients in Australia
      in 1997 were estimated to be A$29 million or 5% of the total cost of stroke. The
      majority of 'out of pocket' costs relate to post-acute care aimed at minimising
      disability and handicap rather than to 'acute' healthcare.

PMID- 14732371
TI  - The relationship between cerebral blood flow and cognitive function in patients
      with brain insult of various etiology.
AB  - The relationship between the mean cerebral blood flow (CBF) and cognitive
      function was investigated in patients with brain insult. This study included 72
      patients aged 24-85 years treated for the following diseases: cerebral infarction
      (21), intracerebral hemorrhage (4), subarachnoid hemorrhage (2), brain tumor
      (14), cerebral contusion (12), normal pressure hydrocephalus (13), Alzheimer's
      disease (2), and others (4). First-pass radionuclide angiography using Technetium
      99m hexamethylpropylene amine oxime (99mTc-HMPAO) was performed for the
      measurement of the mean CBF, and the Sturb-Black Mental Status Examination for
      the neuropsychological evaluation. The mean CBF and the score of the
      neuropsychological test were significantly reduced compared with those of the age
      matched controls. Regardless of etiology, the mean CBF and the score of
      neuropsychological test were significantly reduced, and a significant correlation
      was observed except for the patients with cerebral contusion. The quantitative
      measurement of CBF using 99mTc-HMPAO is reliable to estimate the
      neuropsychological state.

PMID- 14732372
TI  - Diagnosis and misdiagnosis of hemifacial spasm: a clinical and video study.
AB  - Early recognition of hemifacial spasm (HFS) is important as it can be effectively
      treated. 203 family physicians participated in a video "test" on HFS. Only 9.4%
      (19/203) were able to diagnose HFS. 94 (46.3%) of them did not know how to manage
      the condition. Twenty-two (10.8%) would use steroids as a treatment and 13 (6.4%)
      felt no treatment was needed. Only 27 (13.3%) indicated that botulinum toxin
      could be employed to treat HFS. The year of graduation of the doctors
      significantly correlated with a correct diagnosis (P<0.05). The low positive
      diagnostic rate (25.7%) of HFS from referrals to the movement disorder clinic
      corroborated findings from the video test.

PMID- 14732373
TI  - Acute myelopathy. Retrospective clinical, laboratory, MRI and outcome analysis of
      49 cases.
AB  - Forty nine consecutive cases of acute myelopathy were related to the following
      pathologies: 31 MS, four spinal cord infarction, four parainfectious, one
      antiphospolipid syndrome and nine of unknown origin. Sensory deficits were most
      frequent in MS and in myelopathy of unknown origin. In spinal cord infarction
      motor deficits and sphincter dysfunction were present in all cases. In
      parainfectious myelopathy sensory-motor deficits and sphincter dysfunction were
      most frequent. Myelopathy extended over less than two vertebral segments in MS
      and in myelopathy of unknown origin. Myelopathy extended over more than two
      vertebral segments in spinal cord infarction and in parainfectious myelopathy.
      The clinical outcome was good in MS, parainfectious myelopathy and myelopathy of
      unknown origin, but poor in spinal cord infarction. Our findings suggest that
      various aetiologies of acute myelopathy may be differentiated on the basis of
      distinct clinical, MRI, laboratory and outcome data.

PMID- 14732374
TI  - Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole
      brain volume and thalamic atrophy.
AB  - Using serial magnetic resonance imaging (MRI), we investigated the relationship
      between diffuse cerebral atrophy, T1 and T2 lesion volumes, mean thalamic volumes
      and clinical progression in patients with established multiple sclerosis (MS).
      Eleven patients were included in this prospective serial study. Cerebral volumes,
      T1 hypointense lesion volumes, and T2 hyperintense lesion volumes at baseline and
      at up to 3 years follow-up were assessed on MRI brain scans. As a putative
      measure of cerebral atrophy mean thalamic volumes were also obtained. The outcome
      measures were the MRI parameters and disability on Kurtzke's expanded disability
      status scale (EDSS). Of the 11 patients 6 worsened clinically as measured by an
      increase of 0.5 or more on the EDSS. Cerebral atrophy occurred in 91% of patients
      and was independent of changes in lesion volumes and was not associated with
      disease progression as determined by the EDSS.

PMID- 14732375
TI  - Surgical treatment of cervical myelopathy of unclear aetiology.
AB  - In some cases neither the clinical pattern nor the findings of magnetic resonance
      imaging (MRI) can help to determine the cause of a cervical myelopathy. The
      differential diagnosis of such cases as a rule includes spondylotic myelopathy, a
      solitary focus of multiple sclerosis and an intramedullary tumour in early stage.
      Worsening of signs and symptoms due to the circumscribed lesion of the spinal
      cord can require surgical treatment, even if no certain diagnosis could be stated
      thus far. The question is how to choose a surgical procedure which is beneficial
      for all three kinds of spinal cord pathology in their initial stage, which at the
      same time does not jeopardise spine and spinal cord and allows secondary surgery
      if needed after the precise nature of the lesion has been assessed. Ventral
      decompression and fusion with or without dorsal decompression seems to be a
      convincing procedure.

PMID- 14732376
TI  - Primary anaplastic glio-neuronal tumor of the pineal gland: a new type of pineal
      neoplasm?
AB  - BACKGROUND: Tumors of the pineal gland are relatively rare. Most are solid,
      infiltrative lesions characterized by either germ cell, glial, or pineal
      parenchymal origin. To our knowledge, none have been described that contain an
      admixture of both anaplastic glial and neuronal elements. CASE REPORT: The
      authors present a case of a primary anaplastic glio-neuronal tumor of the pineal
      gland in a 78-year-old gentleman who presented with hydrocephalus. The patient
      underwent an endoscopic third ventriculostomy for treatment of his hydrocephalus
      as well as tumor biopsy under endoscopic visualization. RESULTS: Sections of the
      tumor displayed a modestly to moderately cellular neoplasm infiltrating the
      residual pineal gland. The majority of the nuclei appeared hyperchromatic,
      spindle-shaped, and pleomorphic, with fibrillary cytoplasmic processes. Rare
      nuclei were round with vesicular chromatin and red nucleoli. Mitotic figures were
      easily identified, despite small sample size. GFAP immunostaining highlighted the
      fibrillar background and cytoplasmic processes while synaptophysin immunostains
      revealed intense, dot-like positivity in the rounder nuclei with vesicular
      chromatin. Although the different nuclear morphologies seen on the hematoxylin
      eosin stained slides suggested both glial and neuronal origin, immunostains were
      required to confirm the presence of dual differentiation. CONCLUSION: We present
      the first case of a primary anaplastic glio-neuronal neoplasm of the pineal
      gland. Increased use of immunostaining may unveil additional cases in the future.
      Furthermore, additional research will be required to determine whether the dual
      differentiation has prognostic significance.

PMID- 14732377
TI  - Images in neuroscience.

PMID- 14732378
TI  - Surgical procedure "simplified retrosigmoid approach" for C-P angle lesions.
AB  - Previously, we reported surgical results of the simplified retrosigmoid approach
      for vestibular nerve sectioning in the cases with intractable vertigo. Here, we
      introduce in details surgical procedures of the simplified retrosigmoid (also
      called "subasterional" here for simplification) approach developed by one of the
      authors (J.H.L.). This approach is to operate cerebello-pontine (C-P) angle
      lesions through a small upper lateral window below the transverse-sigmoid
      junction. The retroauricular 4-5 cm skin incision, triangular craniectomy 2 cm in
      width, dural opening and closure, special considerations, and reconstruction of
      the skull defect were outlined. The bony landmarks for triangle craniectomy below
      asterion were described in detail. The C-P angle was appropriately approached for
      microvascular decompression, removal of C-P angle tumors, and vestibular nerve
      resection. This subasterional approach was characterized by short operation time
      of 1-3 h and less postoperative discomforts compared to the conventional
      retrosigmoid approach.

PMID- 14732379
TI  - Acute atlanto-axial post-operative subluxation following posterior C1/2 fusion.
AB  - Two cases referred with acute post-operative C1/2 subluxation following posterior
      fusion are reported. Both cases had initial treatment for atlanto-axial
      instability with posterior cable (Brooks and interspinous) and graft techniques,
      and placed immediately in a Philadelphia collar. One case was found to have
      subluxed immediately post-operatively when failing to breathe following reversal
      of anaesthetic agents, and despite immediate realignment and reoperation was left
      with a significant quadriparesis. The other patient was noted to have subluxed on
      routine X-ray on day 4, and had no neurological deficit before or after
      reoperation. Risk factors for this dangerous complication are discussed and the
      techniques of C1/2 posterior fusion and stabilization are reviewed in detail.
      Surgeons performing atlanto-axial stabilization procedures should be familiar
      with and have expertize in the complete range of techniques described and choose
      the one most appropriate for the patient's individual requirements.

PMID- 14732380
TI  - A patient with Wallenberg's syndrome induced by severe cough.
AB  - A 45-year-old man developed severe cough with cervical pain. The patient was
      unable to hold an upright position. The origin of the right posterior inferior
      cerebellar artery was not enhanced by angiography. MRI showed a high signal
      intensity string-like structure of the right vertebral artery. In young patients,
      Wallenberg's syndrome related to mild head trauma has been reported. However,
      none of the previous studies related to vertebral arterial dissection was induced
      by severe cough. When cervical pain is present in young patients with severe
      cough, MRI should be performed to evaluate the possibility of vertebral arterial
      dissection.

PMID- 14732381
TI  - A case study of the resolution of paediatric dysphagia following brainstem
      injury: clinical and instrumental assessment.
AB  - The coexistance of a swallowing impairment can severely impact upon the medical
      condition and recovery of a child with traumatic brain injury [ref.: Journal of
      Head Trauma Rehabilitation 9 (1) (1994) 43]. Limited data exist on the
      progression or outcome of dysphagia in the paediatric population with brainstem
      injury. The present prospective study documents the resolution of dysphagia in a
      14-year-old female post-brainstem injury using clinical, radiological and
      endoscopic evaluations of swallowing. The subject presented with a pattern of
      severe oral-motor and oropharyngeal swallowing impairment post-injury that
      resolved rapidly for the initial 12 weeks, slowed to gradual progress for weeks
      12-20, and then plateaued at 20 weeks post-injury. Whilst a clinically functional
      swallow was present at 10 months post-injury, radiological examination revealed a
      number of residual physiological impairments, reduced swallowing efficiency, and
      reduced independence for feeding, indicating a potential increased risk for
      aspiration. The data highlight the need for early and continued evaluation and
      intensive treatment programs, to focus on the underlying physiological swallowing
      impairment post-brainstem injury, and to help offset any potential deleterious
      effects of aspiration that may affect patient recovery, such as pneumonia.

PMID- 14732382
TI  - Haemorrhagic brain metastasis from a thymic carcinoma.
AB  - Brain metastasis from thymic carcinoma is extremely rare, and there is still no
      consensus regarding the best management of thymic metastasis to the central
      nervous system. Here, we report the first-known Australian case. A review of the
      current literature and the characteristics of thymic tumours with brain
      metastasis indicate that aggressive management may be able to improve long-term
      outcomes for these patients. A 49-year-old man presented 2 weeks after
      thoracotomy for thymic carcinoma resection with a 2-day history of headache,
      right-sided weakness and expressive dysphasia. CT and MR scans revealed two
      metastatic brain lesions, one within the left frontal lobe with cystic necrosis
      and haemorrhage, the other deep in the parietal lobe adjacent to the left
      ventricle with a lesser degree of haemorrhage. The patient underwent frameless
      stereotactic craniotomy for excision of the frontal lesion. Histopathology
      confirmed poorly differentiated thymic carcinoma. Post-operatively his weakness
      and speech improved dramatically, and he was discharged home within a week, with
      radiotherapy and chemotherapy to follow. However, he represented with rapidly
      worsening symptoms and died within a week. Thymic carcinoma is a rare tumour,
      displaying malignant features clinically and histopathologically with local
      invasion to adjacent organs. Metastasis is predominantly to lung, bone, liver and
      kidney, with less predilection for the central nervous system. Treatment for
      thymic carcinoma is multimodal, but outcome remains poor and life expectancy is
      very short when brain metastasis with haemorrhage is present.

PMID- 14732383
TI  - Paradoxical embolism secondary to ovarian carcinoma resulting in stroke.
AB  - A middle aged woman presented with a posterior fossa stroke after an elective ear
      nose and throat procedure. The occurrence of a paradoxical embolism was
      suspected. The evidence for this and a discussion about this condition are
      presented.

PMID- 14732384
TI  - Dissection of the superior cerebellar artery: a report of two cases and review of
      the literature.
AB  - Arterial dissections frequently involve the main trunk of the posterior
      circulation and are recognised as an important cause of stroke in young
      individuals. However, dissection confined to cerebellar arteries is rare. We
      encountered two patients with superior cerebellar artery (SCA) dissection. A 37
      year-old man presented with dysarthria, right limb ataxia, and severe headache.
      Magnetic resonance imaging revealed cerebellar infarction in the right SCA
      territory. Angiography demonstrated stenosis and fusiform dilation of the SCA in
      the anterior pontine segment. Recovery with antiplatelet treatment was nearly
      complete. A 45-year-old man was admitted with decreased consciousness after
      sudden onset of headache. Computed tomography demonstrated subarachnoid
      haemorrhage with hydrocephalus. Angiography revealed fusiform dilation of the
      left SCA in the anterior pontine segment. After ventricular drainage,
      endovascular embolisation was performed without ischaemic complications. The
      patient's condition improved sufficiently to return to daily life. In our search
      only four reported cases involved the SCA. Clinical manifestation and treatment
      for patients with cerebellar arterial dissections are discussed.

PMID- 14732385
TI  - Ganglioglioma of the spinal cord: report of two cases and review of literature.
AB  - Ganglioglioma can involve any part of the central nervous system. Mostly
      ganglioglioma occur in temporal lobe. Spinal cord ganglioglioma is a very rare
      entity. We report two cases of cervico-dorsal region ganglioglioma, who underwent
      complete surgical excision. In the postoperative period they had transient
      deterioration of their neurological status that gradually recovered with follow
      up.

PMID- 14732386
TI  - Pleomorphic xanthoastrocytoma: report of two cases and review of the prognostic
      factors.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a superficially located, rare glial tumour
      first described in 1979. It affects young patients, who often present with
      seizures. The tumour has a relatively favourable prognosis, but 15-20% progress
      to malignancy. We describe two cases of PXA, both with benign features at
      presentation, one of which underwent anaplastic transformation. Surgery remains
      the mainstay of treatment. Factors influencing clinical outcome include extent of
      resection, and histological features such as mitotic index, necrosis and
      lymphocytic infiltration. The roles of radiotherapy and chemotherapy remain
      undefined. We advocate lifelong follow-up and establishment of a central registry
      in order to further the understanding of this infrequently encountered tumour.

PMID- 14732387
TI  - Acoustic schwannoma and petroclival meningioma occurring as collision tumours: a
      case report.
AB  - A case of a collision tumour comprising of an acoustic schwannoma and a
      petroclival meningioma in a 30-year old male patient is described. Both of these
      tumours were resected through a retrosigmoid route. The caudal portion of the
      mass was an acoustic schwannoma while the rostral portion was a distinct well
      defined petroclival meningioma. The occurrence of an acoustic schwannoma and a
      petroclival meningioma in 'collision' has never been reported. The pathogenesis
      of such a rare entity is discussed and the relevant literature is briefly
      reviewed.

PMID- 14732388
TI  - Shunt dysfunction due to calcification of a ventriculo-peritoneal shunt: a case
      report.
AB  - Calcification and related dysfunction of ventriculo-peritoneal shunts are rare
      events in neurosurgical practice. Shunt calcification causes shunt dysfunction in
      two ways, namely disconnection and obstruction. We present a 16-year-old girl
      with shunt malfunction due to disconnection secondary to calcification. The shunt
      tubing fractured during attempted removal and some of the remaining components,
      including the ventricular catheter, had to be left in situ. The shunt was revised
      and the patients symptoms resolved. Replacement of the calcified and perished
      shunt components with a new shunt is essential. Aggressive surgical manipulation
      for removal of the remaining shunt components is not advisable as this may
      increase morbidity and mortality.

PMID- 14732389
TI  - Bilateral occipital condylar fracture. Case report about successful treatment
      with SOMI brace.
AB  - Treatment guidelines for occipital condyle fractures (OCFs) are not established.
      Options for unilateral OCF have been discussed in the literature, but not for
      bilateral cases. We describe a bilateral OCF type II (according to the
      Anderson/Montesano classification) in a 30-year-old patient, where immobilisation
      in a SOMI brace (sternal occipital mandibular immobilisation) was successfully
      used.

PMID- 14732390
TI  - Giant mucoceles of the frontal sinus: a series and review.
AB  - Giant mucoceles of the frontal sinus are a rare pathology but their recognition
      is important in the differential diagnosis of paediatric proptosis and fronto
      orbital lesions. Four patients with giant mucoceles of the frontal sinus were
      retrospectively analyzed. All the patients were females in the paediatric age
      group presenting with massive cosmetically unacceptable bony swelling in the
      frontal region along with unilateral extra-axial proptosis. Radiological imaging
      revealed giant mucoceles of the frontal sinus with extracranial, orbital and
      anterior cranial fossa extension. One patient had co-existent craniofacial
      fibrous dysplasia. Single stage surgery was performed in three patients and two
      stage surgery in one. Fronto-orbital craniotomy, removal of the posterior wall of
      the sinus, obliteration of the sinus and its ostium, dural repair and remodeling
      cranioplasty were performed. Histopathological examination revealed mucoceles in
      all, and co-existant fibrous dysplasia in one patient. All the patients made
      excellent cosmetic recoveries with complete resolution of their visual symptoms.
      Their clinical presentation, radiological manifestations and treatment modalities
      are analyzed and an extensive review of the literature is presented. Our case of
      giant frontal mucocele associated with fibrous dysplasia is furthermore the first
      such report in the existing medical literature.

PMID- 14732393
TI  - Myogenic defects in myotonic dystrophy.
AB  - Myogenesis is the developmental program that generates and regenerates skeletal
      muscle. This process is impaired in patients afflicted with myotonic dystrophy
      type 1 (DM1). Muscle development is disrupted in infants born with congenital
      DM1, and recent evidence suggests that defective regeneration may contribute to
      muscle weakness and wasting in affected adults. DM1 represents the first example
      of a human disease that is caused, at least in part, by pathogenic mRNA. Cell
      culture models have been used to demonstrate that mutant DM1 mRNA takes on a gain
      of-function and inhibits myoblast differentiation. Although the molecular
      mechanism(s) by which this mutant mRNA disrupts myogenesis is not fully
      understood, recent findings suggest that anomalous RNA-protein interactions have
      downstream consequences that compromise key myogenic factors. In this review, we
      revisit morphological studies that revealed the nature of myogenic abnormalities
      seen in patients, describe cell culture systems that have been used to
      investigate this phenotype and discuss recent discoveries that for the first time
      have identified myogenic events that are disrupted in DM1.

PMID- 14732394
TI  - The worm's sense of smell. Development of functional diversity in the
      chemosensory system of Caenorhabditis elegans.
AB  - Animals sense their chemical environment using multiple chemosensory neuron
      types, each of which exhibits characteristic response properties. The
      chemosensory neurons of the nematode Caenorhabditis elegans provide an excellent
      system in which to explore the developmental mechanisms giving rise to this
      functional diversity. In this review, we discuss the principles underlying the
      patterning, generation, differentiation, and diversification of chemosensory
      neuron subtypes in C. elegans. Current knowledge of the molecular mechanisms
      underlying each of these individual steps is derived from work in different model
      organisms. It is essential to describe the complete developmental pathways in
      each organism to determine whether functional diversification in chemosensory
      systems is achieved via conserved or novel mechanisms. Such a complete
      description may be possible in C. elegans.

PMID- 14732395
TI  - bHLH genes cath5 and cNSCL1 promote bFGF-stimulated RPE cells to
      transdifferentiate toward retinal ganglion cells.
AB  - The molecular mechanism of retinal ganglion cell (RGC) genesis and development is
      not well understood. Published data suggest that the process may involve two bHLH
      genes, ath5 and NSCL1. Gain-of-function studies show that ath5 increases RGC
      production in the developing retina. We examined whether two chick genes, cath5
      and cNSCL1, can guide retinal pigment epithelial (RPE) cells to
      transdifferentiate toward RGCs. Ectopic expression of cath5 and cNSCL1 in
      cultured chick RPE cells was achieved through retroviral transduction. cath5
      alone was unable to induce de novo expression of early RGC markers, such as RA4
      antigen, neurofilament (160 kDa), and a neurofilament-associated antigen.
      However, cath5 induced the expression of these proteins when the RPE cells were
      cultured with medium supplemented with bFGF. Since bFGF alone can induce only RA4
      antigen, the expression of the additional RGC markers reflects a synergism
      between cath5 and bFGF in promoting RPE transdifferentiation toward RGCs.
      Morphologically, the RA4(+) cells in bFGF + cath5 cultures appeared more neuron
      like than those generated by bFGF alone. cNSCL1 also promoted bFGF-stimulated RPE
      cells to transdifferentiate toward RGCs that expressed RA4 antigen, N-CAM, Islet
      1, neurofilament, and neurofilament-associated antigen. We found that cath5
      induced cNSCL1 expression, but not vice versa. Our data suggest that cath5 or
      cNSCL1 alone was insufficient to induce RPE transdifferentiation into RGCs, but
      could further neural differentiation initiated by bFGF. We propose that intrinsic
      factors act synergistically with extrinsic factors during RGC genesis and
      development.

PMID- 14732396
TI  - Developmental regulation of Notch signaling genes in the embryonic pituitary:
      Prop1 deficiency affects Notch2 expression.
AB  - Normal development of the pituitary gland requires coordination between the
      maintenance of a progenitor cell pool and the selection of progenitor cells for
      differentiation. As Notch signaling controls progenitor cell differentiation in
      many embryonic tissues, we investigated the involvement of this important
      developmental pathway in the embryonic pituitary. We report that expression of
      Notch signaling genes is spatially and temporally regulated in pituitary
      embryogenesis and implicate Notch2 in the differentiation of several cell
      lineages. Notch2, Notch3, and Dll1 are initially expressed by most cells within
      the pituitary primordium and become restricted to a subset of the progenitor cell
      pool as differentiated pituitary cells begin to appear. Mutations in the
      transcription factor Prop1 interfere with pituitary growth and cell
      specification, although the mechanism is unknown. Notch2 expression is nearly
      absent in the developing pituitaries of Prop1 mutant mice, but unaltered in some
      other panhypopituitary mutants, revealing that Prop1 is directly or indirectly
      required for normal Notch2 expression. Transgenic overexpression of Prop1 is not
      sufficient for enhancement of endogenous Notch2 expression, indicating that there
      are multiple inputs into this pathway. Dll3 is expressed only in the presumptive
      corticotrope and melanotrope cells. Analysis of Dll3 null mutants indicates that
      Dll3 is not required for specification of these two cell types, although there
      may be functional overlap with Dll1. The spatial and temporal expression patterns
      of Notch signaling genes in the pituitary suggest overlapping roles in pituitary
      growth and cell specification.

PMID- 14732397
TI  - A C-type lectin associated and translocated with cortical granules during oocyte
      maturation and egg fertilization in fish.
AB  - Oocyte maturation and egg fertilization in both vertebrates and invertebrates are
      marked by orchestrated cytoplasmic translocation of secretory vesicles known as
      cortical granules. It is thought that such redistribution of cellular content is
      critical for asymmetrical cell division during early development, but the
      mechanism and regulation of the process is poorly understood. Here we report the
      identification, purification and cDNA cloning of a C-type lectin from oocytes of
      a freshwater fish species gibel carp (Carassius auratus gibelio). The purified
      protein has been demonstrated to have lectin activity and to be a Ca(2+)
      dependent C-type lectin by hemagglutination activity assay. Immunocytochemistry
      revealed that the lectin is associated with cortical granules, gradually
      translocated to the cell surface during oocyte maturation, and discharged to the
      egg envelope upon fertilization. Interestingly, the lectin becomes phosphorylated
      on threonine residues upon induction of exocytosis by fertilization and returns
      to its original state after morula stage of embryonic development, suggesting
      that this posttranslational modification may represent a critical molecular
      switch for early embryonic development.

PMID- 14732398
TI  - Drosophila Tbx6-related gene, Dorsocross, mediates high levels of Dpp and Scw
      signal required for the development of amnioserosa and wing disc primordium.
AB  - Regional differentiation along the dorsoventral (DV) axis of the Drosophila
      embryo primarily depends on a graded BMP signaling activity generated by
      Decapentaplegic (Dpp) and Screw (Scw). We have identified triplicated Dpp and Scw
      target genes Dorsocross1, 2 and 3 (Doc1, 2, 3) that have a conserved T-box domain
      related to the vertebrate Tbx6 subfamily and act redundantly to induce dorsal
      structures. Doc genes are expressed in the dorsal region in the early blastoderm.
      After gastrulation, newly expressed Doc appears in a segmental pattern in the
      ectoderm. This expression correlates spatially with the second phase of Dpp
      expression in the ectoderm. Doc expression in the early blastoderm is abolished
      in either dpp or scw mutant embryos, whereas the ectodermal segmented expression
      depends only on Dpp. Inactivation of Doc genes with RNAi dramatically affected
      the development of amnioserosa and wing disc primordia, both of which depend on
      high levels of BMP signaling, although leg disc primordium, which depends on low
      levels of BMP, remained intact. Doc1 mRNA expressed in Xenopus embryos induced
      ventral mesoderm, suppressed activin-induced events and induced Xvent genes,
      which are analogous to the effects of native Tbx6 and its upstream regulator, BMP
      4. These results suggest that the Tbx6 subfamily act in the BMP signaling pathway
      required for embryonic patterning in both animals.

PMID- 14732399
TI  - Heart and head defects in mice lacking pairs of connexins.
AB  - Gene ablation studies in mice have revealed roles for gap junction proteins
      (connexins) in heart development. Of the 20 connexins in vertebrates, four are
      expressed in developing heart: connexin37 (Cx37), connexin40 (Cx40), connexin43
      (Cx43), and connexin45 (Cx45). Although each cardiac connexin has a different
      pattern of expression, some heart cells coexpress multiple connexins during
      cardiac morphogenesis. Since different connexins could have overlapping
      functions, some developmental phenotypes may only become evident when more than
      one connexin is ablated. In this study, we interbred Cx40(-/-) and Cx43(-/-) mice
      to generate mice lacking both Cx40 and Cx43. Cx40(-/-)Cx43(-/-) mice die around
      embryonic day 12.5 (E12.5), much earlier than either Cx40(-/-) or Cx43(-/-) mice,
      and they exhibit malformed hearts with ventricles that are abnormally rotated,
      suggesting a looping defect. Some Cx40(-/-)Cx43(-/-) animals also develop head
      defects characteristic of exencephaly. In addition, we examined mice lacking both
      Cx40 and Cx37 and found a high incidence of atrial and ventricular septal defects
      at birth. These results provide further evidence for the importance of gap
      junctions in embryonic development. Moreover, ablating different pairs of cardiac
      connexins results in distinct heart defects, suggesting both common and unique
      functions for Cx40, Cx43, and Cx37 during cardiac morphogenesis.

PMID- 14732400
TI  - Nek2B stimulates zygotic centrosome assembly in Xenopus laevis in a kinase
      independent manner.
AB  - Pronuclear migration and formation of the first mitotic spindle depend upon
      assembly of a functional zygotic centrosome. For most animals, this involves both
      paternal and maternal contributions as sperm basal bodies are converted into
      centrosomes competent for microtubule nucleation through recruitment of egg
      proteins. Nek2B is a vertebrate NIMA-related protein kinase required for
      centrosome assembly, as its depletion from egg extracts delays microtubule aster
      formation from sperm basal bodies. Using Xenopus as a model system, we now show
      that protein expression of Nek2B begins during mid-oogenesis and increases
      further upon oocyte maturation. This is regulated, at least in part, at the level
      of protein translation. Nek2B protein is weakly phosphorylated in mitotic egg
      extracts but its recruitment to the sperm basal body, which occurs independently
      of its kinase activity, stimulates its phosphorylation, possibly through
      sequestration from a phosphatase present in mitotic egg cytoplasm. Importantly,
      although Nek2B is not required to organize acentrosomal microtubule asters, we
      show that addition of either active or kinase-dead recombinant Nek2B can restore
      centrosome assembly in a dose-dependent manner to a depleted extract. These
      results support a model in which maternal Nek2B acts to promote assembly of a
      functional zygotic centrosome in a kinase-independent manner.

PMID- 14732401
TI  - Requirement of protein tyrosine kinase and phosphatase activities for human sperm
      exocytosis.
AB  - The acrosome is a membrane-limited granule that overlies the nucleus of the
      mature spermatozoon. In response to physiological or pharmacological stimuli,
      sperm undergo calcium-dependent exocytosis termed the acrosome reaction, which is
      an absolute prerequisite for fertilization. Protein tyrosine phosphorylation and
      dephosphorylation are a mechanisms by which multiple cellular events are
      regulated. Here we report that calcium induces tyrosine phosphorylation in
      streptolysin O (SLO)-permeabilized human sperm. As expected, pretreatment with
      tyrphostin A47-a tyrosine kinase inhibitor-abolishes the calcium effect.
      Interestingly, the calcium-induced increase in tyrosine phosphorylation has a
      functional correlate in sperm exocytosis. Masking of phosphotyrosyl groups with a
      specific antibody or inhibition of tyrosine kinases with genistein, tyrphostin
      A47, and tyrphostin A51 prevent the acrosome reaction. By reversibly sequestering
      intra-acrosomal calcium with a photo-inhibitable chelator, we show a requirement
      for protein tyrosine phosphorylation late in the exocytotic pathway, after the
      efflux of intra-acrosomal calcium. Both mouse and human sperm contain highly
      active tyrosine phosphatases. Importantly, this activity declines when sperm are
      incubated under capacitating conditions. Inhibition of tyrosine phosphatases with
      pervanadate, bis(N,N-dimethylhydroxoamido)hydroxovanadate, ethyl-3,4-dephostatin,
      and phenylarsine oxide prevents the acrosome reaction. Our results show that both
      tyrosine kinases and phosphatases play a central role in sperm exocytosis.

PMID- 14732403
TI  - A cAMP receptor-like G protein-coupled receptor with roles in growth regulation
      and development.
AB  - Dictyostelium discoideum uses G protein-mediated signal transduction for many
      vegetative and developmental functions, suggesting the existence of G protein
      coupled receptors (GPCRs) other than the four known cyclic adenosine
      monophosphate (cAMP) receptors (cAR1-4). Sequences of the cAMP receptors were
      used to identify Dictyostelium genes encoding cAMP receptor-like proteins, CrlA
      C. Limited sequence identity between these putative GPCRs and the cAMP receptors
      suggests the Crl receptors are unlikely to be receptors for cAMP. The crl genes
      are expressed at various times during growth and the developmental life cycle.
      Disruption of individual crl genes did not impair chemotactic responses to folic
      acid or cAMP or alter cAMP-dependent aggregation. However, crlA(-) mutants grew
      to a higher cell density than did wild-type cells and high-copy-number crlA
      expression vectors were detrimental to cell viability, suggesting that CrlA is a
      negative regulator of cell growth. In addition, crlA(-) mutants produce large
      aggregates with delayed anterior tip formation indicating a role for the CrlA
      receptor in the development of the anterior prestalk cell region. The scarcity of
      GFP-expressing crlA(-) mutants in the anterior prestalk cell region of chimeric
      organisms supports a cell-autonomous role for the CrlA receptor in prestalk cell
      differentiation.

PMID- 14732402
TI  - A PTP-PEST-like protein affects alpha5beta1-integrin-dependent matrix assembly,
      cell adhesion, and migration in Xenopus gastrula.
AB  - During amphibian gastrulation, mesodermal cell movements depend on both cell-cell
      and cell-matrix interactions. Ectodermal cells from the blastocoel roof use
      alpha5beta1 integrins to assemble a fibronectin-rich extracellular matrix on
      which mesodermal cells migrate using the same alpha5beta1 integrin. In this
      report, we show that the tyrosine phosphatase xPTP-PESTr can prevent fibronectin
      fibril formation when overexpressed in ectodermal cells resulting in delayed
      gastrulation. In addition, isolated ectodermal cells overexpressing xPTP-PESTr
      are able to spread on fibronectin using the alpha5beta1 integrin in the absence
      of activin-A induction and before the onset of gastrulation. We further show that
      while the inhibition of fibrillogenesis depends on the phosphatase activity of
      xPTP-PESTr, induction of cell spreading does not. Finally, while cell spreading
      is usually associated with cell migration, xPTP-PESTr promotes ectodermal cell
      spreading on fibronectin but also reduces cell migration in response to activin
      A, suggesting an adverse effect on cell translocation. We propose that xPTP-PESTr
      overexpression adversely affect cell migration by preventing de-adhesion of cells
      from the substrate.

PMID- 14732404
TI  - Characterization of C. elegans RING finger protein 1, a binding partner of
      ubiquitin-conjugating enzyme 1.
AB  - In a yeast two-hybrid screen, RING finger protein 1 (RFP-1) and UBR1 were
      identified as potential binding partners of C. elegans UBC-1, a ubiquitin
      conjugating enzyme with a high degree of identity to S. cerevisiae UBC2/RAD6. The
      interaction of RFP-1 and UBC-1 was confirmed by co-immunoprecipitation
      experiments. Yeast interaction trap experiments mapped the region of interaction
      to the basic N-terminal 313 residues of RFP-1. The acidic carboxy-terminal
      extension of UBC-1 was not required for the interaction with RFP-1. Western blot
      analysis and indirect immunohistochemical staining show that RFP-1 is present in
      embryos, larvae, and adults, where it is found in intestinal, nerve ring,
      pharyngeal, gonadal, and oocyte cell nuclei. Double-stranded RNA interference
      experiments against rfp-1 indicate that this gene is required for L1 development,
      vulval development, and for egg laying. By contrast, RNA interference against ubc
      1 gave no obvious phenotype, suggesting that ubc-1 is nonessential or is
      functionally redundant.

PMID- 14732405
TI  - Conserved elements in Pax6 intron 7 involved in (auto)regulation and alternative
      transcription.
AB  - Pax6 is a transcription factor with an essential role in eye, central nervous
      system, and pancreas development. Its expression pattern is restricted to these
      specific domains within the developing embryo. Here four conserved elements are
      identified in Pax6 intron 7, showing a high level of sequence conservation
      between human, mouse, pufferfish, and zebrafish. Three of these are shown to act
      as cis-regulatory elements, directing expression of a reporter gene to distinct
      subsets of the Pax6 expression domain. CE1 regulates gene expression in late eye
      development, CE2 drives expression in the diencephalon and in the developing
      heart tube where Pax6 is not normally expressed, while CE3 directs expression in
      rhombencephalon. CE2 is shown to be autoregulated in the diencephalon, responding
      to absence of Pax6. We identify a highly conserved Pax6 recognition site and
      demonstrate its ability to bind Pax6 specifically. CE1 is embedded in a CpG
      island, and we identify a novel Pax6 transcript which initiates from this region.
      Functional analysis of evolutionary conserved sequences pinpoints novel cis
      acting elements that govern the regulation of the complex spatio-temporal and
      quantitative expression of Pax6.

PMID- 14732406
TI  - Multiple regulatory elements with spatially and temporally distinct activities
      control the expression of the epithelial differentiation gene lin-26 in C.
      elegans.
AB  - Epithelial differentiation is a very early event during development of most
      species. The nematode Caenorhabditis elegans, with its well-defined and invariant
      lineage, offers the possibility to link cell lineage, cell fate specification and
      gene regulation during epithelial differentiation. Here, we focus on the
      regulation of the gene lin-26, which is required for proper differentiation of
      epithelial cells in the ectoderm and mesoderm (somatic gonad). lin-26 expression
      starts in early embryos and remains on throughout development, in many cell types
      originating from different sublineages. Using GFP reporters and mutant rescue
      assays, we performed a molecular dissection of the lin-26 promoter and could
      identify almost all elements required to establish its complex spatial and
      temporal expression. Most of these elements act redundantly, or synergistically
      once combined, to drive expression in cells related by function. We also show
      that lin-26 promoter elements mediate activation in the epidermis (hypodermis) by
      the GATA factor ELT-1, or repression in the foregut (pharynx) by the FoxA protein
      PHA-4. Taken together, our data indicate that lin-26 regulation is achieved to a
      large extent through tissue-specific cis-regulatory elements.

PMID- 14732407
TI  - Comprehensive transcriptome analysis of differentiation of embryonic stem cells
      into midbrain and hindbrain neurons.
AB  - Neurogenesis is one of the most complex events in embryonic development. However,
      little information is available regarding the molecular events that occur during
      neurogenesis. To identify regulatory genes and underlying mechanisms involved in
      the differentiation of embryonic stem (ES) cells to neurons, gene expression
      profiling was performed using cDNA microarrays. In mouse ES cells, we compared
      the gene expression of each differentiated cell stage using a five-stage lineage
      selection method. Of 10,368 genes, 1633 (16%) known regulatory genes were
      differentially expressed at least 2-fold or greater at one or more stages. At
      stage 3, during which ES cells differentiate into neural stem cells, modulation
      of nearly 1000 genes was observed. Most of transcription factors (Otx2, Ebf-3,
      Ptx3, Sox4, 13, 18, engrailed, Irx2, Pax8, and Lim3), signaling molecules (Wnt,
      TGF, and Shh family members), and extracellular matrix/adhesion molecules
      (collagens, MAPs, and NCAM) were up-regulated. However, some genes which may play
      important roles in maintaining the pluripotency of ES cells (Kruppel-like factor
      2, 4, 5, 9, myeloblast oncogene like2, ZFP 57, and Esg-1) were down-regulated.
      The many genes identified with this approach that are modulated during
      neurogenesis will facilitate studies of the mechanisms underlying ES cell
      differentiation, neural induction, and neurogenesis.

PMID- 14732408
TI  - The core enhancer is essential for proper timing of MyoD activation in limb buds
      and branchial arches.
AB  - Transgenic analyses have defined two transcriptional enhancers that regulate MyoD
      expression in mammals, the core enhancer and distal regulatory region; these
      enhancers exhibit complementary activities and together are sufficient to
      recapitulate MyoD expression in developing and mature skeletal muscle. The core
      enhancer is activated in presumptive muscle cells and determined myoblasts,
      suggesting an important role in initiating MyoD expression. Here, targeted
      mutagenesis in the mouse is used to identify necessary and redundant core
      enhancer functions. The core enhancer is essential for the timely initiation of
      MyoD expression in limb buds and branchial arches, as enhancer deletion delayed
      MyoD activation by 1 to 2 days in these muscle lineages. Functionally, this delay
      in MyoD transcription delayed the onset of muscle differentiation, as assayed by
      expression of the gene encoding for the early differentiation marker, Myogenin.
      In addition to these lineage-specific defects, a generalized, modest reduction in
      MyoD expression was observed in all muscle lineages and at all embryonic stages
      examined. Interestingly, however, a specific defect was not observed in the
      nascent myocytes at the medial and lateral aspects of the myotome, suggesting the
      existence of at least one other enhancer with this specificity. The core enhancer
      was also dispensable for Myf-5- and Pax-3-dependent regulation of MyoD
      transcription. These data demonstrate a differential requirement for core
      enhancer activity in muscle lineages derived from migratory precursors and
      suggest redundancy in cis regulatory mechanisms controlling myotomal MyoD
      expression.

PMID- 14732409
TI  - Learning at a distance I. Statistical learning of non-adjacent dependencies.
AB  - In earlier work we have shown that adults, young children, and infants are
      capable of computing transitional probabilities among adjacent syllables in
      rapidly presented streams of speech, and of using these statistics to group
      adjacent syllables into word-like units. In the present experiments we ask
      whether adult learners are also capable of such computations when the only
      available patterns occur in non-adjacent elements. In the first experiment, we
      present streams of speech in which precisely the same kinds of syllable
      regularities occur as in our previous studies, except that the patterned
      relations among syllables occur between non-adjacent syllables (with an
      intervening syllable that is unrelated). Under these circumstances we do not
      obtain our previous results: learners are quite poor at acquiring regular
      relations among non-adjacent syllables, even when the patterns are objectively
      quite simple. In subsequent experiments we show that learners are, in contrast,
      quite capable of acquiring patterned relations among non-adjacent segments-both
      non-adjacent consonants (with an intervening vocalic segment that is unrelated)
      and non-adjacent vowels (with an intervening consonantal segment that is
      unrelated). Finally, we discuss why human learners display these strong
      differences in learning differing types of non-adjacent regularities, and we
      conclude by suggesting that these contrasts in learnability may account for why
      human languages display non-adjacent regularities of one type much more widely
      than non-adjacent regularities of the other type.

PMID- 14732410
TI  - Imaginal perspective switches in remembered environments: transformation versus
      interference accounts.
AB  - Imaginal perspective switches are often considered to be difficult, because they
      call for additional cognitive transformations of object coordinates
      (transformation hypothesis). Recent research suggests that problems can also
      result from conflicts between incompatible sensorimotor and cognitive object
      location codes during response specification and selection (interference
      hypothesis). Three experiments tested contrasting predictions of both accounts.
      Volunteers had to point to unseen object locations after imagined self-rotations
      and self-translations. Results revealed larger pointing latencies and errors for
      rotations as compared to translations, and monotic latency and error increases
      for both tasks as a function of the disparity of object directions between real
      and imagined perspective. Provision of advance information about the to-be
      imagined perspective left both effects unchanged. These results, together with
      those from a systematic error analysis, deliver clear support for an interference
      account of imaginal perspective switches in remembered surroundings.

PMID- 14732411
TI  - Infants' comprehension of toy replicas as symbols for real objects.
AB  - Infants' understanding of toy model-real exemplar relations was assessed through
      preferential looking and habituation tasks. Results from the preferential looking
      task suggest that 18-month toddlers are just beginning to demonstrate
      comprehension of symbolic relations between iconic models and their real object
      counterparts. Performance of 10- and 14-month-old infants in the preferential
      looking task did not improve when across-domain pairs of videos were used in
      place of within-domain pairs. Habituation task results indicated that 10-month
      olds do not comprehend symbolic relations between miniature toy replicas and
      their "real" counterparts, but that such understanding begins to emerge by age 14
      months. Interactions between symbolic processing and early lexical development
      are considered, as are methodological implications for the study of infant
      categorization.

PMID- 14732412
TI  - Evolution of encounter group methods in therapeutic communities for substance
      abusers.
AB  - Some literature indicates an evolution in the concept underlying therapeutic
      communities (TC, for substance abusers), where encounter group methods evolved
      from harsh confrontation to dialogue and discussion. The literally transcribed
      proceedings of two similar encounter groups, held at a 20-year interval, were
      systematically analyzed on four main variables: direction of communication
      sequences and associated behavior, emotions, and attitudes of all participants
      (staff members and "older" and "newer" residents). In general, "toward" and
      "back" messages are relatively more balanced in the "new" encounter (2000) as
      compared with the "old" encounter (1980). Furthermore, associated behavior in the
      "new" encounter is found to be more supportive, whereas ventilated emotions are
      more negative than in the "old" encounter. The number of communication units
      within the "old" and "new" encounter, characterizing a positive or negative
      attitude, seems to have remained stable over the years. These findings support
      the reported evolution in encounter groups, where the focus has moved from mutual
      confrontation toward balanced and respectful dialogue.

PMID- 14732413
TI  - Sexual abuse and smoking among college student women.
AB  - Despite the potential influence of sexual abuse in childhood and adulthood on
      smoking among women, few studies have examined these variables. In this
      exploratory study, 296 women completed an anonymous survey. Results revealed that
      women who were sexually abused as children were 3.8 times more likely than their
      non-abused counterparts to be current smokers and were 2.1 times more likely to
      have initiated smoking before the age of 14. In all analyses, sexual abuse was a
      better predictor of smoking than were status variables. These preliminary
      findings highlight sexual abuse in childhood as a gender-specific stressor that
      increases girls and women's risk for smoking. Hence, sexual abuse is worthy of
      further investigation as well as of inclusion in new gender-tailored smoking
      prevention and cessation programs.

PMID- 14732414
TI  - A psychometric analysis of the self-regulation questionnaire.
AB  - The self-regulation questionnaire (SRQ) is a 63-item instrument designed to
      measure the generalized ability to regulate behavior so as to achieve desired
      future outcomes. This study extended previous psychometric evaluations of the SRQ
      by determining the factor structure and internal consistency of the SRQ and
      providing convergent and discriminant evidence for its validity. Participants
      were undergraduates (N=391; 55% women) from two consecutive semesters (n(1)=208;
      n(2)=183). A single-factor solution emerged (31 items), invariant across gender
      and semester. These items were combined to create a short version of the SRQ
      (SSRQ; alpha=.92), which was highly correlated with the original SRQ (r=.96).
      Unrelated to demographic variables and alcohol use, the SSRQ correlated
      significantly with alcohol-related problems. The association between the SSRQ and
      problems remained even after controlling for social desirability and alcohol
      consumption. These results support the use of the SSRQ in young adult samples.
      Further psychometric evaluation of the SSRQ is necessary, however, to further
      establish its validity and utility as a measure of generalized self-regulation
      capacity.

PMID- 14732415
TI  - Recollections and repercussions of the first inhaled cigarette.
AB  - CONTEXT: It has not been determined if a youth's reaction to the first smoking
      experience is predictive of future nicotine dependence, or whether the impact of
      the first cigarette can be altered by manipulating levels of tar, nicotine and
      menthol. OBJECTIVE: To determine if the recalled response to the first cigarette
      is predictive of the development of symptoms of nicotine dependence and whether
      it is influenced by the type of cigarette smoked. DESIGN AND SETTING: A
      retrospective/prospective longitudinal study of the natural history of nicotine
      dependence employing individual interviews conducted three times annually in two
      urban school systems over 3 years. Subjects were asked to recall their first
      smoking experience. PARTICIPANTS: A cohort of 237 subjects who had inhaled on a
      cigarette. MAIN OUTCOME MEASURES: Symptoms associated with smoking; the Hooked on
      Nicotine Checklist of 10 symptoms of dependence. RESULTS: Reactions to the
      initial smoking experience were unrelated to gender or cigarette brand, strength
      or mentholation. Relaxation in response to the first inhalation was the strongest
      predictor of symptoms of nicotine dependence. Dizziness and nausea were also
      independent predictors of dependence symptoms. CONCLUSIONS: The data suggest that
      increased sensitivity to nicotine as manifested by relaxation, dizziness, or
      nausea in response to the first exposure to nicotine represents a risk factor for
      the development of nicotine dependence.

PMID- 14732416
TI  - Does a childhood history of externalizing problems predict smoking during
      pregnancy?
AB  - While the demographic characteristics of women who smoke during pregnancy are
      well established, less is known about psychiatric characteristics that may
      differentiate among persistent smokers, spontaneous quitters, and nonsmokers. The
      purpose of the present study was to test the hypothesis that a history of
      externalizing problems is related to persistent smoking during pregnancy.
      Participants included 93 pregnant women (mean age=28 years; 89% non-Hispanic
      White; 46% persistent smokers; and 16% spontaneous quitters). Externalizing
      problems, as evidenced by conduct disorder (CD) and attention deficit
      hyperactivity disorder (ADHD), were assessed using diagnostic interviews. History
      of CD and ADHD varied by smoking status, with persistent smokers most likely to
      have a history of both disorders and exhibiting the highest levels of
      symptomatology. In multivariate analyses, a history of CD, but not ADHD symptoms,
      distinguished women who persisted in smoking during pregnancy from spontaneous
      quitters. Results suggest that a childhood history of conduct problems is a risk
      factor for maternal smoking during pregnancy and that psychiatric history is
      important to consider in developing more targeted cessation interventions.

PMID- 14732417
TI  - Developing discrepancy within self-regulation theory: use of personalized
      normative feedback and personal strivings with heavy-drinking college students.
AB  - Efforts to reduce the frequency of high-risk drinking have included the use of
      motivational interventions. Both the technique used in motivational interventions
      and an underlying theory of behavior change (i.e., self-regulation theory) invoke
      the construct of discrepancy development. This study was designed to determine
      whether techniques purported to develop discrepancy actually do so and to compare
      methods of developing discrepancy on indices of intention to reduce alcohol use.
      Male and female college drinkers (N=92) were selected if they reported two or
      more binge episodes in the last month, or scored 4 or higher on the Rutgers
      Alcohol Problem Index (RAPI). Participants were randomly assigned by gender to
      three conditions all conducted in a small group format: attention-control,
      personalized normative feedback (PNF), and personal strivings assessment (PSA).
      Personalized normative feedback was designed to develop discrepancy based on
      behavioral comparisons of self and others. Personal strivings assessment was
      designed to develop discrepancy between current and ideal self. It was
      hypothesized that participants who engage in discrepancy building activities
      would experience discrepancy specific to the activity in which they engaged, and
      that all participants who developed discrepancy would show higher levels of
      intention to reduce alcohol use. Results indicated that only the personalized
      normative feedback increased discrepancy and intention to reduce alcohol use.

PMID- 14732418
TI  - Prospective association of peer influence, school engagement, drinking
      expectancies, and parent expectations with drinking initiation among sixth
      graders.
AB  - Early initiation of drinking increases the lifetime risk for substance abuse and
      other serious health and social problems. An understanding of the predictors of
      early initiation is needed if successful preventive interventions are to be
      developed. Surveys were completed by 1009 sixth grade students at the beginning
      (Time 1) and end (Time 2) of the school year in four schools in one suburban
      school district. At Time 1, 55/1009 (5.5%) reported drinking in the past 30 days.
      From Time 1 to Time 2, the percentage of drinkers increase to 127/1009 (10.9%) of
      whom 101 were new drinkers. In multiple logistic regression analyses, school
      engagement was negatively associated and peer influence and drinking expectancies
      were positively associated with drinking initiation. A significant interaction
      was found between drinking expectancies and parental expectations. Among sixth
      graders with high drinking expectancies, those with low parental expectations for
      their behavior were 2.6 times more likely to start drinking than those with
      parents with high expectations for their behavior. Positive drinking expectancies
      were significantly associated with drinking initiation only among teens who
      believed their parents did not hold strong expectations for them not to drink.
      This finding held for boys and girls, Blacks and Whites and was particularly
      strong for Black youth. This finding provides new information about the
      moderating effect of parental expectations on drinking expectancies among early
      adolescents.

PMID- 14732419
TI  - Positive and negative consequences of alcohol consumption in college students.
AB  - While the negative consequences of alcohol use in college students are well
      known, less is known about the relationships of these consequences to alcohol
      consumption patterns. Further, almost no research has been conducted examining
      students' positive alcohol-related consequences. The current study examines the
      nature and frequency of positive and negative alcohol-related consequences, the
      relationship of these consequences to alcohol consumption patterns, and the
      impact of these consequences on subsequent drinking intentions. Findings indicate
      that college student drinking does indeed involve many negative consequences,
      some of which are quite serious, but that students also experience many positive
      consequences. In fact, they report their encounters with positive consequences as
      being more extreme and more frequent than their encounters with negative
      consequences. Further, consuming more alcohol is related to experiencing more
      positive and more negative consequences, as well as more extremely positive
      positive encounters, but not more extremely negative negative ones. Finally,
      participants reported that their positive and negative consequences would
      influence their future drinking decisions in a number of different ways. Future
      research directions and implications for interventions are discussed.

PMID- 14732420
TI  - Risk factors for pathological gambling.
AB  - To better understand pathological gambling, potential risk factors were assessed
      within three domains--gambling behaviors, substance abuse and other problem
      behaviors, and sociodemographic factors. A random-digit-dial telephone survey was
      conducted in 1999-2000 with a representative sample of the U.S. population aged
      18 or older. The current analyses uses data from the 2168 respondents who gambled
      in the year before the interview. Gambling measures included the Diagnostic
      Interview Schedule (DIS)-IV for pathological gambling, frequency of 15 types of
      gambling, and size of win or loss on the last occasion. Other measures included
      the quantity and frequency of alcohol consumption, frequency of illicit drug use
      and criminal offending, and the DIS-IV for alcohol and drug abuse and dependence.
      Results showed that casino gambling is associated with a high risk of gambling
      pathology. Lottery, cards, and bingo are associated with a moderately high risk
      of gambling pathology. Participation in a greater number of types of gambling is
      strongly predictive of gambling pathology, even after frequency of gambling and
      size of win or loss are taken into account. Alcohol abuse is strongly predictive
      of gambling pathology, even with gambling behaviors held constant. Minority and
      low socioeconomic status (SES) group members have higher levels of gambling
      pathology than other groups after all other factors are considered.

PMID- 14732422
TI  - Predictors of current need to smoke in inmates of a smoke-free jail.
AB  - A popular correctional policy has been the implementation of smoking bans for
      inmates. Although there is little cigarette smoking research with this
      population, research with other groups suggests that high levels of post
      cessation cravings are associated with smoking relapse. The present study
      analyzed the relationship of demographic and smoking history variables, length of
      time incarcerated, and future intention to smoke upon release with current need
      to smoke in jail inmates. Participants were 150 male inmates housed in a smoke
      free county jail who were intensively interviewed about smoking behavior as part
      of a larger study. Results indicated that stated future intention to smoke
      predicted current need to smoke in inmates, while length of time in jail did not.
      Nicotine dependence was not related either to the current need to smoke or future
      intention to smoke. These findings were consistent with previous inmate smoking
      research and have clinical implications for inmate smokers.

PMID- 14732421
TI  - Social reinforcement of substance abuse treatment aftercare participation: Impact
      on outcome.
AB  - Although adherence to aftercare therapy in substance abuse treatment is
      associated with improved outcome, little research has explored the effects of
      adherence interventions on outcome. We compared 20 graduates of our 28-day
      intensive treatment program who received a standard aftercare orientation with 20
      graduates who received this intervention plus social reinforcement of aftercare
      group therapy attendance. The social reinforcement group showed less alcohol use
      than the standard care group at a 6-month follow-up assessment as measured by the
      Addiction Severity Index (ASI), but not less drug use. Additionally, compared to
      standard care, the social reinforcement participants were more likely to be
      abstinent at the 6-month follow up (76% vs. 40%). The groups did not differ on
      hospital readmission rates over a 12-month follow-up period. Additionally, the
      social reinforcement group showed better long-term aftercare attendance compared
      to the standard care group.

PMID- 14732423
TI  - Cotinine as a biomarker of systemic nicotine exposure in spit tobacco users.
AB  - Unlike cigarette smokers, spit tobacco (ST) users absorb a significant amount of
      nicotine through the gastrointestinal tract while swallowing tobacco juice. The
      majority of the absorbed nicotine is rapidly converted to cotinine during first
      pass hepatic metabolism. This process potentially compromises the utility of
      cotinine as a biomarker for systemic nicotine exposure in ST users. To
      investigate this question, we correlated nicotine and cotinine concentrations
      with clinical measures of ST use in 68 daily ST users enrolled in a non-nicotine
      pharmacologic intervention trial. We found that a higher frequency of swallowing
      tobacco juice (P=.007) was an independent predictor of higher serum cotinine
      concentrations. Serum nicotine concentrations, on the other hand, were not
      correlated with a higher frequency of swallowing. In the absence of a reliable
      way to measure frequency of swallowing, we conclude that cotinine should not be
      used for guiding clinical decisions that depend upon a precise quantification of
      systemic nicotine exposure, such as tailored nicotine replacement therapy.

PMID- 14732424
TI  - Characteristics of cigarette smokers seeking treatment for cessation versus
      reduction.
AB  - Comparisons were made between cigarette smokers seeking treatment to quit smoking
      and cigarette smokers seeking treatment to reduce the number of cigarettes they
      smoke. Potential subjects were recruited from the local metropolitan area by
      advertisement in the local media. A total of 665 cigarette smokers telephoned our
      clinic to seek treatment for smoking cessation and 565 cigarette smokers
      telephoned to seek treatment to gradually reduce the number of cigarettes they
      smoke but not quit smoking. Potential subjects were instructed to call the clinic
      to find out additional information about the studies, and while on the telephone
      they were asked questions pertaining to tobacco use and health status. The
      results show that the two populations are similar in many respects with the
      following exceptions: smokers seeking treatment to reduce cigarette use tend to
      smoke more cigarettes per day, are less motivated to quit, make fewer quit
      attempts, drink more alcoholic beverages per day, and have more health problems
      (Ps<.05). These results indicate that cigarette smokers seeking treatment for
      smoking reduction but not cessation may be more dependent smokers who experience
      more medical disorders.

PMID- 14732425
TI  - Factors associated with adverse reactions to cocaine among a sample of long-term,
      high-dose users in Sao Paulo, Brazil.
AB  - This cross-sectional survey investigates the frequency of adverse cocaine
      reactions and associated factors among regular cocaine misusers. A sample of 332
      cocaine misusers from a range of treatment and nontreatment settings in Sao
      Paulo, Brazil, were interviewed using a questionnaire that includes the Severity
      of Dependence Scale (SDS), the General Health Questionnaire (GHQ-28), the CAGE,
      and an eight-item questionnaire investigating the frequency of specific adverse
      cocaine reactions. The most commonly described reactions were hot flushes (84%),
      uncontrollable shaking (76%), and feeling ill (75%). The most severe symptoms and
      least common were convulsions or fits (18%) and passing out (21%). Frequency of
      adverse reactions to cocaine was positively associated with out-of-treatment
      status, severity of cocaine dependence, ever having injected cocaine, using
      tranquilisers with cocaine, and GHQ score. Adverse reactions to cocaine are
      common among regular cocaine users. Some of the adverse effects, especially those
      on the heart and central nervous system, are potentially fatal. Preventive
      strategies should be developed to reduce the risk of adverse cocaine reactions.
      The findings are discussed in relation to the type of interventions that might be
      developed and lines of future research.

PMID- 14732426
TI  - Gender differences in the association among nicotine dependence, body image,
      depression, and anxiety within a college population.
AB  - Previous research has linked female weight concerns and smoking. This study
      examined whether poor body image and other eating disorder variables, after
      controlling for symptoms of anxiety and depression, were predictive of smoking
      severity in a sample of 478 college students (n=215 males, n=246 females).
      Contrary to our hypotheses and recent research, the predictors were not
      associated with nicotine dependence for females (R(2)=.00), and only dieting was
      negatively associated with nicotine dependence for males. These findings might be
      attributable to differences in how nicotine dependence is operationalized, the
      use of point prevalence symptom data versus lifetime prevalence of
      psychopathology, the severity of psychopathology in the present sample, or the
      use of a cross-sectional as opposed to a longitudinal design.

PMID- 14732427
TI  - Evaluation of an alternative methodology for investigating leadership and binge
      drinking among sorority members.
AB  - Recent research suggests that leaders in Greek organizations use alcohol more
      frequently and more heavily than non-leaders in Greek organizations. These
      results carry considerable implications for the majority of existing alcohol
      education programs that rely heavily on peer modeling. The purpose of the present
      study was to determine whether a more complex and realistic assessment of
      leadership involvement produced different results than the previous study.
      Results from 327 women in five randomly selected sororities provide evidence that
      binge drinking is related to some negative academic outcomes, but that a
      significant relationship between binge drinking and leadership involvement in
      Greek organizations does not exist. Furthermore, the results provide evidence
      that leadership styles do not influence the leadership involvement-binge drinking
      relationship.

PMID- 14732428
TI  - "Who gets in?" Recruitment and screening processes of outpatient substance abuse
      trials.
AB  - A brief telephone-screening interview was conducted with 1759 callers seeking
      treatment for substance abuse at the Treatment Research Clinic (TRC) over a 16
      month period. The purpose of this study was to examine the effectiveness of
      various recruitment methods in attracting eligible participants and to identify
      screening variables that characterized eligible and ineligible callers. Callers
      referred by friends and family were more likely to be eligible than callers from
      other referral sources. Callers seeking treatment for cocaine abuse who reported
      more severe alcohol/substance problems were more likely to be eligible for
      treatment protocols, while those with severe problems in other psychosocial areas
      (legal, medical, and psychiatric) were more often excluded. Alcohol- and nicotine
      dependent callers reporting severe alcohol problems were more likely to be
      eligible but otherwise were not different from callers who were ineligible. The
      effectiveness of recruitment methods may not be the same for different types of
      substance use disorders. This study underscores the importance of having a
      sensitive screening assessment for recruiting a homogeneous yet representative
      sample for outpatient substance abuse clinical trials.

PMID- 14732429
TI  - Awareness of independence of events and erroneous perceptions while gambling.
AB  - The majority of individuals behaves and think irrationally when gambling. The
      fundamental mistake committed is to rely on previous events to predict the
      outcome of the game. This study examines if information, reminding the players
      about independence between events, while gambling influences their perception of
      the game and their motivation to continue gambling. Thirty-one occasional
      gamblers, 18 men and 13 women aged 20-64 years old (M=40), participated in the
      study. The hypotheses predicted that reminders about independence of events would
      decrease the number of erroneous perceptions and that the motivation to pursue
      the game would be weaker among participants who received reminders. Results
      confirmed both hypotheses. Interventions based on these results could
      significantly increase responsible gambling.

PMID- 14732430
TI  - Verification of adolescent self-reported smoking.
AB  - Smoking and the validity of information obtained on it is often questioned in
      view of the widespread belief that adolescents tend to under- or over-report the
      habit. The aim here was to verify smoking habits as reported in a questionnaire
      given in conjunction with dental examinations by asking participants directly
      whether they smoked or not and performing biochemical measurements of thiocyanate
      in the saliva and carbon monoxide in the expired air. The series consisted of 150
      pupils in the ninth grade (age 15 years). The reports in the questionnaires
      seemed to provide a reliable estimate of adolescent smoking, the sensitivity of
      the method being 81-96%, specificity 77-95%. Biochemical verification or control
      of smoking proved needless in normal dental practice. Accepting information
      offered by the patient provides a good starting point for health education and
      work motivating and supporting of self-directed breaking of the habit.

PMID- 14732431
TI  - Prevalence and correlates of past-year substance use, abuse, and dependence in a
      suburban community sample of high-school students.
AB  - To assess the severity of substance use, abuse and dependence in a community
      sample of high school students, a cross-sectional survey was conducted in a
      suburban New Jersey community. Participants, a sample of 9th to 12th graders from
      six high schools (N=1044), completed a self-administered questionnaire after
      obtaining active parental consent. The measure of substance use disorders was
      based on 27 specially designed questions that approximate the DSM-IV criteria for
      abuse and dependence. Equivalent multivariate logit models were used to estimate
      the significant correlates for both use and dependence/abuse. The prevalence of
      drug use in this sample was similar to the national average for all drugs except
      alcohol. A total of 16.4% of the surveyed students reported either abuse or
      dependence symptoms with alcohol in the past year. The rates of abuse/dependence
      for marijuana and other illicit drugs were 13.4% and 3.9%. The rate of nicotine
      dependence was 8.0%. The logit models designed to examine the correlates of
      substance use showed minimal predictive or correlative value in explaining
      substance abuse or dependence in adolescence. More research is needed to identify
      and understand the factors leading adolescents from drug use to abuse or
      dependence.

PMID- 14732432
TI  - Smoking among female prisoners: an ignored public health epidemic.
AB  - The Mississippi Department of Corrections (MDOC) surveyed 866 female prisoners
      about tobacco use and interest in a smoking cessation program. The 27-item
      questionnaire assessed basic demographic information; type of tobacco used,
      amounts and frequency of use, triggers for use, health status, family tobacco use
      and health status, money spent on tobacco products, cessation attempts,
      motivation and self-efficacy for smoking cessation, and interest in participating
      in a smoking cessation program. The majority of female inmates (73.9%) were
      current tobacco users and 71.5% smoked cigarettes, with a mean of 14.6 cigarettes
      per day (cpd). Approximately 12.5% of current smokers reported a tobacco-related
      medical problem. Most (60.6%) had made at least one attempt to quit smoking and
      only 24.5% felt "very confident" that they could quit if they made an attempt.
      Overall, 64.2% of the smokers reported interest in participating in the smoking
      cessation program, with heavier smokers (71.4%) reporting the most interest in
      enrolling in the program. The high percentage of current tobacco users, high
      level of interest in smoking cessation, and presence of smoking-related health
      problems indicate a tremendous public and correctional health problem that is
      being ignored.

PMID- 14732433
TI  - Different variables are associated with help-seeking patterns and long-term
      outcomes among problem drinkers.
AB  - This study investigated variables associated with help-seeking for drinking
      problems and with long-term drinking outcomes. In a 3 x 2 design, problem
      drinkers (N=167) were selected according to their help-seeking history [no
      assistance (NA), Alcoholics Anonymous (AA) only, or treatment plus AA (TxAA)] and
      current drinking status [resolved abstinent (RA) for >2 years or non-resolved
      (NR) active drinkers]. Drinking practices and problems, influences on help
      seeking, and life events were assessed retrospectively during structured
      interviews. Participant reports were verified through collateral or reliability
      interviews. Stable resolution was associated with heavier drinking and greater
      negative life events before resolution. Seeking help, especially from treatment,
      was associated with greater psychosocial problems and higher dependence levels.
      The results indicate that different dimensions of drinking problems are
      associated with help-seeking and drinking outcomes, and suggest ways to increase
      help-seeking.

PMID- 14732435
TI  - Vernalization and epigenetics: how plants remember winter.
AB  - One of the remarkable aspects of the promotion of flowering by vernalization is
      that plants have evolved the ability to measure a complete winter season of cold
      and to 'remember' this prior cold exposure in the spring. Recent work in
      Arabidopsis demonstrates the molecular basis of this memory of winter:
      vernalization causes changes in the chromatin structure of a flowering repressor
      gene, FLOWERING LOCUS C (FLC), that switch this gene into a repressed state that
      is mitotically stable. A key component of the vernalization pathway,
      VERNALIZATION INSENSITIVE3 (VIN3), which is a PHD-domain-containing protein, is
      induced only after a prolonged period of cold. VIN3 is involved in initiating the
      modification of FLC chromatin structure. The stable silencing of FLC also
      requires the DNA-binding protein VERNALIZATION1 (VRN1) and the polycomb-group
      protein VRN2.

PMID- 14732436
TI  - Epigenetic control of plant development: new layers of complexity.
AB  - Important aspects of plant development are under epigenetic control, that is,
      under the control of heritable changes in gene expression that are not associated
      with alterations in DNA sequence. It is becoming clear that RNA molecules play a
      key role in epigenetic gene regulation by providing sequence specificity for the
      targeting of developmentally important genes. RNA-based control of gene
      expression can be exerted posttranscriptionally by interfering with transcript
      stability or translation. Moreover, RNA molecules also appear to direct
      developmentally relevant gene regulation at the transcriptional level by
      modifying chromatin structure and/or DNA methylation.

PMID- 14732437
TI  - Posttranscriptional control of plant development.
AB  - Genetic studies have provided increasing evidence that proteins involved in all
      aspects of RNA metabolism, such as RNA processing, transport, stability, and
      translation, are required for plant development and for plants' responses to the
      environment. Such proteins act in floral transition, floral patterning, and
      signaling by abscisic acid, low temperature and circadian rhythms. Although some
      of these proteins belong to core RNA metabolic machineries, others may have more
      specialized cellular functions. Despite the limited knowledge of the underlying
      molecular mechanisms, posttranscriptional regulation is known to play a key role
      in the control of plant development.

PMID- 14732438
TI  - Integrating signals in stomatal development.
AB  - Stomata are specialized epidermal structures that control the exchange of water
      and carbon dioxide between the plant and the atmosphere. The classical
      developmental mechanisms that define cell fate and tissue patterning - cell
      lineage, cell-cell interactions and signals from a distance - are employed to
      make stomata and to define their density and distribution within the epidermis.
      Recent work has shown that two genes that are involved in stomatal pattern may
      encode components of a classical cell-surface-receptor-mediated signaling
      cascade. Additional work has suggested that signals from the overlying cuticle
      and the underlying mesophyll also influence stomatal pattern. These findings
      highlight the need for models that explain how the signals that regulate stomatal
      development are integrated and how they act to regulate cell polarity, the cell
      cycle and, ultimately, cell fate.

PMID- 14732439
TI  - Cell expansion in roots.
AB  - Cell expansion in roots is crucial for the exploration and exploitation of the
      soil substrate and the plethora of activities that roots engage in. Expansion
      requires the coordinated activities of many cell processes. Central to this is
      the control of ion transport during vacuolar growth, which mediates the increase
      in cell size and the concomitant production of new wall and membrane at the
      surface of growing cells. The cytoskeleton plays an important role in growth and
      the control of growth direction. Evidence is accumulating to show that plant
      hormones also coordinate cell expansion throughout the plant by controlling the
      activities of growth-regulating DELLA proteins.

PMID- 14732440
TI  - The ethylene signaling pathway: new insights.
AB  - During the past decade, molecular genetic studies on the reference plant
      Arabidopsis have established a largely linear signal transduction pathway for the
      response to ethylene gas. The biochemical modes of action of many of the
      signaling components are still unresolved. During the past year, however,
      progress in several areas has been made on several fronts. The different
      approaches used have included a functional study of the activity of the receptor
      His kinase, the determination of the ethylene receptor signaling complex at the
      endoplasmic reticulum and of the regulation of CONSTITUTIVE TRIPLE RESPONSE1
      (CTR1) activity by these receptors, the identification of a unique MITOGEN
      ACTIVATED PROTEIN KINASE (MAPK) cascade, the cloning and characterization of
      numerous ETHYLENE INSENSITIVE3 (EIN3)/EIN3-like (EIL) transcription factors from
      many plant species, and the integration of the ethylene and jasmonate response
      pathways via the ETHYLENE RESPONSE FACTOR (ERF) family of transcription factors.
      The elucidation of the biochemical mechanisms of ethylene signal transduction and
      the identification of new components in the ethylene response pathway in
      Arabidopsis are providing a framework for understanding how all plants sense and
      respond to ethylene.

PMID- 14732441
TI  - Global expression profiling applied to plant development.
AB  - Plant development is controlled by both endogenous genetic programs and responses
      to exogenous signals. Microarray experiments are being used to identify the genes
      involved in these developmental processes. Most of the analyses conducted to date
      have been conducted on whole organs. Although these studies have provided
      valuable information, they are limited by the composite nature of plant organs
      that consist of multiple cell types. Technical advances that have made it
      possible to study global patterns of gene expression in individual cell types
      promise to increase greatly the information revealed by microarray experiments.

PMID- 14732442
TI  - Determination of cell fate in apical meristems.
AB  - Although roots and shoots exhibit profound differences in their pattern of
      organogenesis, both apices share the capacity for indeterminate growth. Ongoing
      molecular and genetic analyses have revealed relatively little overlap between
      the genes that regulate organogenesis in the root and shoot apices. In the shoot,
      an ensemble of transcription factors lays the foundations for the leaf, in which
      indeterminacy is exchanged for more limited and polarized growth. Class-I KNOX
      genes are downregulated in the anlagen of the leaf early in its establishment,
      but are maintained in other regions of the shoot apex. This persistent expression
      of KNOX genes may serve to prevent the precocious determination of apical initial
      derivatives, and thus may allow the production of a large number of pluripotent
      cells from a relatively small number of stem cells. Greater commonality between
      roots and shoots is seen in mechanisms that underlie histogenesis and radial
      patterning processes. Recent work suggests that undetermined stem cells in both
      the root and the shoot may be maintained by related mechanisms, which feature
      regulation of WUSCHEL-like organizer activities by feedback mechanisms that
      involve receptor-like kinases.

PMID- 14732443
TI  - Shaping up: the genetic control of leaf shape.
AB  - Leaf initiation at the shoot apical meristem involves a balance between cell
      proliferation and commitment to make primordia. Several genes, such as CLAVATA1,
      CLAVATA3, WUSCHEL, KNOTTED1, and PHANTASTICA, play key roles in these processes.
      When expressed in the leaf primordium, however, these 'meristem' genes can
      profoundly affect leaf shape and size, possibly by regulating hormone gradients
      and transport. The KNOTTED1-like genes are involved in regulating changes in
      hormonal levels. Recent studies have elaborated on the role that hormones, such
      as auxin, play in releasing biophysical constraints on leaf initiation and
      growth. Final leaf form is elaborated by a coordination of these hormonally
      regulated processes, cell division and cellular differentiation.

PMID- 14732444
TI  - Shoot branching.
AB  - The mature form of a plant shoot system is an expression of several genetically
      controlled traits, many of which are also environmentally regulated. A major
      component of this architectural variation is the degree of shoot branching.
      Recent results indicate conserved mechanisms for shoot branch development across
      the monocots and eudicots. The existence of a novel long-range branch-inhibiting
      signal has been inferred from studies of branching mutants in pea and
      Arabidopsis.

PMID- 14732445
TI  - Modeling plant growth and development.
AB  - Computational plant models or 'virtual plants' are increasingly seen as a useful
      tool for comprehending complex relationships between gene function, plant
      physiology, plant development, and the resulting plant form. The theory of L
      systems, which was introduced by Lindemayer in 1968, has led to a well
      established methodology for simulating the branching architecture of plants. Many
      current architectural models provide insights into the mechanisms of plant
      development by incorporating physiological processes, such as the transport and
      allocation of carbon. Other models aim at elucidating the geometry of plant
      organs, including flower petals and apical meristems, and are beginning to
      address the relationship between patterns of gene expression and the resulting
      plant form.

PMID- 14732446
TI  - Conservation and diversity in flower land.
AB  - During the past decade, enormous progress has been made in understanding the
      molecular regulation of flower development. In particular, homeotic genes that
      determine the identity of the floral organs have been characterised from
      different flowering plants, revealing considerable conservation among angiosperm
      species. On the other hand, evolutionary diversification has led to enormous
      variation in flower morphology. Increasing numbers of reports have described
      differences in the regulation, redundancy and function of homeotic genes from
      various species. These fundamentals of floral organ specification are therefore
      an ideal subject for comparative analyses of flower development, which will lead
      to a better understanding of plant evolution, plant development and the
      complexity of molecular mechanisms that control flower development and
      morphology.

PMID- 14732447
TI  - Evolution of developmental traits.
AB  - The evolution of plant development can be studied in many different ways, each of
      which provides new insights into how plants have been modified over evolutionary
      time. DNA sequencing shows that most developmental genes are under purifying
      selection and that obvious adaptive change in proteins is rare. This may indicate
      that most change occurs in cis-regulatory sequences, that tests for detecting
      selection lack power, or both. Gene duplications are common and often correlate
      with divergence of function, as predicted by theory. Studies of gene expression
      illuminate similarities among structures in disparate plant groups and indicate
      that the same genes have been deployed repeatedly for similar developmental ends.
      Comparative functional studies remain uncommon, but promise to illuminate how
      changing proteins lead to changes in development. Precise characterization of
      phenotypes by studies of developmental morphology is beginning to occur in some
      taxonomic groups. The genetic variation necessary for morphological change must
      originate as allelic polymorphism within populations; such polymorphism has been
      identified in grasses and in sunflowers, although it is often cryptic.

PMID- 14732448
TI  - Dietary L-carnitine increases plasma leptin concentrations of gestating sows fed
      one meal per day.
AB  - Thirty-four sows (parity=1.8; BW=206 kg) were used to determine the influence of
      L-carnitine and/or chromium tripicolinate on plasma leptin concentrations of
      gestating sows fed one meal daily. Treatments were arranged in a 2 x 2 factorial
      with main effects of carnitine (0 or 50 ppm) and chromium (0 or 200 ppb). Diets
      were fed for approximately 167 days (through one gestation, the following
      lactation, the interval from weaning to estrus, and 28 days into the following
      gestation) prior to blood collection. Leptin concentration was determined in
      plasma that was collected at feeding, every 15 min for the first 3h after
      feeding, and at 6, 9, 15, 20, and 24h after feeding. Sows fed diets containing
      carnitine had greater (P<0.02) overall mean plasma leptin concentrations and
      greater (P<0.05) leptin concentrations at 2.25, 3, 6, 15, 20, and 24h after
      feeding compared to sows fed either the control diet or the diet containing
      chromium. Leptin concentrations of sows fed diets containing carnitine also were
      greater (P<0.05) than control sows at 2.5 and 2.75 h postprandial and greater
      than (P<0.05) sows fed diets with both carnitine and chromium at 6h after
      feeding. Chromium had no effect (P>0.10) on plasma leptin concentration. These
      results suggest that dietary carnitine, but not chromium, increases circulating
      leptin in gestating sows fed one meal per day. These results may help to explain
      the improvements in reproductive function previously observed from feeding sows
      diets containing carnitine.

PMID- 14732449
TI  - Porcine leptin alters isolated adipocyte glucose and fatty acid metabolism.
AB  - This study examined if leptin can acutely affect glucose or fatty acid metabolism
      in pig adipocytes and whether leptin's actions on lipogenesis are manifested
      through interaction with insulin or growth hormone. Subcutaneous adipose tissue
      was obtained from approximately 55 kg crossbred barrows at the USDA abattoir.
      Isolated adipocytes were prepared using a collagenase procedure. Experiments
      assessed U-14C-glucose or 1-14C-palmitate metabolism in isolated adipocytes
      exposed to: basal medium (control), 100 nM insulin, 100 ng/ml porcine growth
      hormone, 100 ng/ml recombinant porcine leptin, and combinations of these
      hormones. Treatments were performed in triplicate and the experiment was repeated
      with adipocytes isolated from five different animals. Cell aliquots (250 microl)
      were added to 1 ml of incubation medium, then incubated for 2h at 37 degrees C
      for measurement of glucose and palmitate oxidation or incorporation into lipid.
      Incubation of isolated adipocytes with insulin increased glucose oxidation rate
      by 18% (P<0.05), while neither growth hormone nor leptin affected glucose
      oxidation (P>0.5). Total lipid synthesis from glucose was increased by
      approximately 25% by 100 nM insulin or insulin+growth hormone (P<0.05).
      Insulin+leptin reduced the insulin response by 37% (P<0.05). The combination of
      all three hormones increased total lipid synthesis by 35%, relative to controls
      (P<0.05), a rate similar to insulin alone. Fatty acid synthesis was elevated by
      insulin (32%, P<0.05) or growth hormone (13%, P<0.05). Leptin had no effect on
      fatty acid synthesis (P>0.05). Leptin reduced the esterification rate by 10%
      (P<0.05). Growth hormone and insulin could overcome leptin's inhibition of
      palmitate esterification (P>0.05).

PMID- 14732450
TI  - beta-Adrenergic receptor agonists increase apoptosis of adipose tissue in mice.
AB  - beta-Adrenergic receptor (beta-AR) agonists increase muscle mass and decrease
      body fat in rodents and livestock. With oral administration, however, the effects
      of beta1-AR and beta2-AR can be different, depending on the species tested. We
      tested the effects of clenbuterol, a beta2-AR agonist, and ractopamine, a
      beta1/beta2-AR agonist, on growth, adiposity and adipose tissue apoptosis in male
      and female mice by feeding diets containing control, 200 ppm clenbuterol, or 200
      or 800 ppm ractopamine. Food intake (FI) was measured daily; body weight (BW) and
      temperatures (BT) were measured on days 0, 3, 7, 10, 14, 17, and 20. On day 21
      mice were sacrificed, body composition was determined using PIXImus densitometry,
      and muscle and adipose tissues were collected. There were no treatment effects on
      BT, FI, BW, feed efficiency or body composition. Retroperitoneal (Rp) and
      epididymal/parametrial (Epi/Par) fat pad masses were reduced in both 800 ppm
      ractopamine (40+/-3mg and 207+/-20mg, respectively) and clenbuterol (35+/-7 mg
      and 211+/-22 mg) treated mice compared to control (66+/-8 mg and 319+/-30 mg,
      P<0.05). Brown adipose tissue (BAT) mass was greater (P<0.05) in clenbuterol
      treated mice compared to other treatments. Adipose tissue apoptosis (% DNA
      fragmentation) was increased in Epi/Par fat pads in clenbuterol (5.2+/-1.1%) and
      800 ppm ractopamine (4.1+/-0.8%) treated mice compared to control (1.7+/-0.4%,
      P<0.05). These findings show that WAT apoptosis can be induced by activation of
      beta-AR in mice, although the mechanism is unknown.

PMID- 14732451
TI  - Effect of short-term fasting on plasma concentrations of leptin and other
      hormones and metabolites in dairy cattle.
AB  - We determined the effects of short-term fasting and refeeding on temporal changes
      in plasma concentrations of leptin, insulin, insulin-like growth factor- 1 (IGF
      1), growth hormone (GH), glucose, and nonesterified fatty acids (NEFA), in early
      lactating cows, non-lactating pregnant cows, and postpubertal heifers. In
      experiment 1, Holstein cows in early lactation were either fed ad libitum
      (Control, n=5) or feed deprived for 48 h (Fasted, n=6). Plasma leptin, insulin,
      and glucose concentrations rapidly declined (P<0.05) within 6h, and IGF-1 by 12h,
      but all these variables sharply returned to control levels (P>0.10) within 2h of
      refeeding. Plasma NEFA and GH concentrations were elevated (P<0.05) by 4 and 36 h
      of fasting and returned to control levels (P>0.10) by 8 and 24h after refeeding,
      respectively. In experiment 2, four ruminally cannulated pregnant non-lactating
      Holstein cows were used in a cross-over design and were fasted for 48 h (Fasted)
      or fasted with partial evacuation of rumen contents (Fasted-Evac). The plasma
      variables measured did not differ (P>0.10) between Fasted and Fasted-Evac cows.
      Plasma leptin, insulin, and IGF-1 concentrations were reduced by 10, 6, and 24h
      of fasting, respectively, in Fasted-Evac cows; and these variables were reduced
      by 24h in Fasted cows (P<0.05). Plasma glucose levels were reduced (P<0.05) by 48
      h of fasting in both groups of fasted animals. Plasma NEFA and GH levels were
      increased (P<0.05) by 12 and 48 h of fasting, respectively. In experiment 3,
      postpubertal Holstein heifers were either fed ad libitum (Control, n=4) or feed
      deprived for 72 h (Fasted, n=5). Concentrations of leptin, insulin, IGF-1, and
      glucose in plasma were reduced (P<0.05) by 24, 10, 24, and 48 h of fasting,
      respectively. Plasma NEFA concentrations increased (P<0.05) by 4h, of fasting
      while GH levels were not significantly (P>0.10) affected by fasting.
      Collectively, our data provide evidence that plasma leptin concentrations are
      reduced with short-term fasting and rebound on refeeding in dairy cattle with the
      response dependent on the physiological state of the animals. Compared to the
      rapid induction of hypoleptinemia with fasting of early lactation cows, the
      fasting-induced hypoleptinemia was delayed in non-lactating cows and postpubertal
      heifers.

PMID- 14732452
TI  - Changes in circulating insulin-like growth factor-I, insulin-like growth factor
      binding proteins, and leptin in weaned pigs infected with Salmonella enterica
      serovar Typhimurium.
AB  - One of the hallmarks of the pathophysiology of enteric disease in young pigs is
      reduced growth performance. This reduction in growth is associated with changes
      in the endocrine somatotropic growth axis. Our laboratory previously demonstrated
      that circulating insulin-like growth factor-I (IGF-I) was reduced in pigs
      infected with Salmonella enterica serovar Typhimurium (S. typhimurium) while
      circulating growth hormone remained unchanged. The objective of the current study
      was to determine if infection with S. typhimurium also was associated with
      changes in circulating IGF binding proteins (IGFBP). In addition, pigs
      experiencing active enteric disease have reduced feed intake. Because this
      inappetence may be related to systemic appetite reduction signals, we also
      evaluated circulating leptin in pigs undergoing active S. typhimurium-induced
      enteric disease. Crossbred pigs were penned in environmentally controlled rooms
      with free access to feed and water. Following an acclimation period, pigs were
      gavaged with 10(10) cfu of S. typhimurium (SAL; n=6) or were given a similar
      volume of sterile growth media (CON; n=6). Rectal temperatures and feed intakes
      were measured daily through 168 h to track the time course of the response to S.
      typhimurium infection. Samples of serum were obtained by jugular venipuncture at
      0, 24, 48, 96 and 168 h after infection. Sera were frozen until evaluation for
      IGF-I by immunoradiometric assay (IRMA). In addition, sera were subjected to
      western ligand blotting utilizing 125I-IGF-I and 125I-IGF-II. Images were
      evaluated for total IGFBP and IGFBP-3 by densitometric analyses. Rectal
      temperature was increased in SAL pigs 24h post-infection (P<0.001) but not at
      other times. Feed intake was reduced in SAL pigs during the intervals 24-72 h
      (P<0.001) and 96-144 h (P<0.05) after infection. Serum IGF-I, expressed as a
      percentage of the 0 h concentration, was reduced in SAL pigs versus CON pigs at
      48 h (28.1+/-18.7% versus 102.2+/-17.1%; P<0.01) and 96 h (20.0+/-18.7% versus
      128.4+/-17.0%; P<0.0001) post-infection. Both total IGFBP and IGFBP-3, as
      estimated by ligand blotting, also were reduced in infected pigs at 48 h
      postchallenge (P<0.05). IGFBPs were similar between the two treatments at other
      sampling times. Concentrations of IGFBP-3 also were estimated utilizing an IRMA
      for human IGFBP-3. Serum IGFBP-3 was reduced in S. typhimurium-infected pigs at
      24 h (P<0.01), 48 h (P<0.001), 96 h (P<0.001), and 168 h (P<0.05). Serum leptin
      levels were similar between SAL and CON pigs. The data suggest that swine enteric
      disease is associated with reduced circulating IGF-I and reductions in total
      IGFBP and IGFBP-3. However, serum leptin was not affected by enteric disease
      challenge.

PMID- 14732453
TI  - Differential effects of the endocrine-disrupting compounds bisphenol-A and
      octylphenol on gonadotropin secretion, in prepubertal ewe lambs.
AB  - This study examined the effects of long-term exposure to the endocrine-disrupting
      compounds (EDCs) Bisphenol-A (BPA) and Octylphenol (OP) on gonadotrophin
      secretion in pre-pubertal female sheep. Four-week-old, female lambs were randomly
      allocated to four groups (n=6), and twice each week treated with i.m. injections
      of either corn oil (vehicle controls), diethylstilbestrol (DES; 0.175mg/kg), BPA
      (3.5mg/kg) or OP (3.5mg/kg). After 5 weeks of treatment, animals were
      ovariectomized (ovx) and ovary weights recorded. Two weeks later, blood samples
      were collected from lambs every 15min for 6h, for LH pulse analysis. Animals were
      then euthanased and adrenal and kidney weight recorded. An age-related increase
      in tonic LH secretion was noted in Control, BPA- and OP-treated lambs, but was
      absent in DES-treated lambs. Following ovx, LH secretion increased in all except
      DES-treated lambs; FSH concentrations increased in all groups. BPA and DES
      significantly suppressed LH pulse frequency (C: 6.7+/-0.3pulses/6h, DES: 1.5+/
      0.8pulses/6h, BPA: 2.3+/-0.8pulses/6h) and amplitude (C: 7.1+/-1.0ng/ml, DES:
      1.9+/-0.6ng/ml, BPA: 1.6+/-0.4ng/ml). OP had no effect on LH secretion
      (Frequency: 5.8+/-0.5pulses/6h, amplitude: 8.0+/-2.0ng/ml). Ovary weight was
      similar among all groups. Results show that chronic in vivo exposure of
      prepubertal female lambs to BPA, at levels lower than those reported previously,
      can have significant effects on LH secretion that are comparable to those seen
      following exposure to the known xenoestrogen, DES. Exposure to an equal dose of
      the EDC OP, over the equivalent period of time was without effect on gonadotropin
      secretion in the prepubertal ewe lamb. These results indicate that exposure of
      prepubertal female lambs to the EDC BPA can induce significant effects on
      gonadotropin secretion, the potential long-term effects of exposure and the
      effects of these changes on reproductive performance and efficacy, therefore,
      merit further study.

PMID- 14732454
TI  - Functional and phylogenetic analyses of a melanocortin-4 receptor mutation in
      domestic pigs.
AB  - The melanocortin-4 receptor (MC4R), a G protein-coupled seven-transmembrane
      receptor, which is expressed in the brain, plays an important role in the control
      of mammalian energy homeostasis. A missense mutation (Asp298Asn) was identified
      in the porcine MC4R gene, which is associated with growth and food intake traits.
      The Asn298 mutation occurs within a highly conserved motif, NPLIY, of all members
      of G protein-coupled receptors; whereas, Asp298 is conserved in all five
      melanocortin receptor subtypes. Functional analysis of the porcine MC4R variant
      was performed with an in vitro gene expression system in 293 cells. Ligand
      binding (NDP-alphaMSH) did not differ between Asp298 and Asn298 MC4R proteins.
      However, the Asn298 MC4R variant was unable to stimulate cAMP production in
      response to NDP-alphaMSH stimulation; whereas, the Asp298 variant could stimulate
      cAMP accumulation. These results demonstrate that the Asp298 is required for
      normal MC4R signaling to the adenylyl cyclase. Sequencing of the MC4R gene of
      seven diverse genera within the Suiformes that include Hippopotamidae (hippos),
      Tayassuidae (peccaries) and Suidae (pigs), revealed 62 nucleotide variations in
      MC4R. Phylogenetic relationships of MC4R variations are consistent with those
      previously described from morphological and physiological data among the
      subfamilies of the Suiformes. These findings revealed that a single missense
      mutation (Asp298Asn) of aspartic acid (Asp) to asparagine (Asn) in MC4R gene
      decreased cAMP content and MC4R signaling, but with no difference in the ligand
      binding was associated with growth and feed intake traits in domestic pigs.

PMID- 14732455
TI  - Variation of the prion gene in chimpanzees and its implication for prion
      diseases.
AB  - In humans, familial prion diseases are linked to mutations in the PRNP gene. We
      have sequenced part of this gene in a large sample of common chimpanzee, Pan
      troglodytes (n=130 chromosomes). No variation in codons 129 and 219 has been
      observed: all chimpanzees were homozygous for the Met allele, which in humans
      increases susceptibility to Creutzfeldt-Jakob disease. We found two sequence
      variants: one is a synonymous polymorphism unique to the chimpanzee at codon 226,
      TAC to TAT (Y), with a TAC allele frequency of 80.6%; the other is a non
      synonymous change at codon 148 (R148H) that falls in the target epitope for some
      common commercial antibodies used for prion diagnostics, and is highly conserved
      across species. The pathogenicity of this mutation is still unknown.

PMID- 14732456
TI  - Reduced G-protein coupling to the GABAB receptor in the nucleus accumbens and the
      medial prefrontal cortex of the rat after chronic treatment with nicotine.
AB  - The effect of repeated administration of nicotine (0.4 mg/kg, daily, s.c., for 14
      days) on GABAB receptor density, affinity and G-protein coupling was investigated
      in the mesocorticolimbic system of the rat brain. Baclofen-stimulated
      [35S]GTPgammaS binding autoradiography revealed that the level of G-protein
      coupling to GABAB receptors was significantly reduced in the medial prefrontal
      cortex and the nucleus accumbens of nicotine-treated rats as compared to vehicle
      injected controls. By contrast, GABAB receptor density and affinity, as revealed
      by [3H]GABA saturation binding autoradiography, were not altered by the nicotine
      exposure in any of the regions examined. Reduced G-protein coupling to the GABAB
      receptor may result in disinhibition of mesocorticolimbic dopaminergic neurones,
      which would contribute to the development of sensitised dopaminergic responses to
      repeated administration of nicotine.

PMID- 14732457
TI  - Permanent focal cerebral ischemia activates erythropoietin receptor in the
      neonatal rat brain.
AB  - Erythropoietin (Epo) has been shown to act as a neurotrophic and neuroprotective
      factor via binding to its receptor (EpoR) which is activated in adult brains
      following hypoxia and ischemia. However, no evidence suggests that cerebral
      ischemia can activate EpoR in the neonatal brain. In the present study, the
      changes in EpoR expression were investigated using a modified model of permanent
      focal cerebral ischemia (FCI) in 7-day-old rat pups. Western blot analysis with
      an anti-rabbit EpoR antibody revealed a significant increase in the EpoR protein
      in the ischemic areas, starting from 6 to 12 h after FCI. Moreover, many EpoR
      positive cells were detected in the ischemic areas from 12 h after FCI, and the
      positive cells were identified as neurons and microglia/macrophage but not
      astrocytes 24 h after FCI. Additionally, double staining with a red in situ
      apoptosis detection kit and the EpoR antibody indicated that EpoR-positive cells
      were in apoptotic cell death in the ischemic area. Therefore, these results
      suggest that EpoR is activated in the ischemic areas of neonatal rats and plays
      an important role in brain injury during development.

PMID- 14732458
TI  - Contrasting neuroprotective and neurotoxic actions of respective metabolites of
      anti-Parkinson drugs rasagiline and selegiline.
AB  - The anti-Parkinson selective irreversible monoamine oxidase B inhibitor drugs,
      rasagiline and selegiline, have been shown to possess neuroprotective activities
      in cell culture and in vivo models. While rasagiline is metabolized to its major
      metabolite aminoindan, selegiline gives rise to L-methamphetamine. Cultured PC-12
      cells in absence of serum and nerve growth factor (NGF) die by an apoptotic
      process. Pretreatment of PC12 cells in absence of serum and NGF for 24 h with
      either rasagiline (1 microM) or selegiline (1 microM) is neuroprotective and anti
      apoptotic as determined by ELISA and MTT tests. However, while aminoindan (1
      microM), the major metabolite of rasagiline does not interfere with the
      neuroprotective activities of rasagiline or selegiline in PC-12 cells deprived of
      serum and NGF, the major metabolite of selegiline, L-methamphetamine (1 microM),
      inhibits them. In contrast to L-methamphetamine, aminoindan is itself is
      neuroprotective in this system. Recently it has been demonstrated that rasagiline
      directly activates PKC-MAP kinase pathway by a concentration and time dependent
      phosphorylation of p42 and p44 MAP kinase. In the present studies the
      neuroprotective activity of rasagiline is blocked by ERK inhibitor, PD98059 (20
      microM), suggesting the involvement of PKC-MAP kinase pathway in the
      neuroprotection. These findings may have implication for the possible disease
      modifying action of rasagiline in treatment of Parkinson's disease.

PMID- 14732459
TI  - Glucose sensitivity in mouse substantia nigra pars reticulata neurons in vitro.
AB  - Glucose sensitivity of substantia nigra pars reticulata (SNr) GABAergic neurons
      was investigated by extracellular recording in acute slice. Approximately two
      thirds of the GABAergic SNr neurons tested exhibited a significant increase in
      spontaneous firing rate as the extracellular glucose concentration was lowered
      from 10 to 4-6 mM. At lower glucose concentrations, a small proportion of these
      glucose-sensitive GABAergic SNr neurons exhibited multiple, robust increases in
      spontaneous firing rate with periods ranging in minutes. Similar changes in
      firing rate of SNr neurons in response to lowered glucose were detected under
      blockade of GABAA, NMDA, and non-NMDA receptors, indicating that mechanisms other
      than those mediated by the major synaptic transmissions in the SNr are involved.
      These findings suggest involvement of previously unknown glucose dependent
      alterations of GABAergic SNr neuronal activity in the central regulation of
      glucose homeostasis.

PMID- 14732460
TI  - N-methyl-D-aspartate receptor and L-type voltage-gated Ca2+ channel activation
      mediate proline-rich tyrosine kinase 2 phosphorylation during cerebral ischemia
      in rats.
AB  - Cerebral ischemia induces rapid efflux of glutamate into the extracellular space
      contributing to excessive activation of glutamate receptors in postsynaptic
      cells, particularly N-methyl-D-aspartate (NMDA) receptors, which triggers the
      neuron lesion through calcium overload. Our studies indicated that cerebral
      ischemia stimulated the rapid activation of nonreceptor tyrosine kinases proline
      rich tyrosine kinase 2 (Pyk2) and Src and the binding to Pyk2 activated the
      latter. Pyk2 activation significantly depends on the increase of the
      intracellular calcium level; blockage of both calcium ion channel NMDA receptors
      and L-type voltage-gated Ca2+ channel (L-VGCC), respectively, could effectively
      inhibit phosphorylation of Pyk2 in early ischemia episodes. Moreover,
      pretreatment with the protein kinase C inhibitor (chelerythrine chloride) reduced
      the ischemia-induced activation of Pyk2. Noticeably, CaMKII, a family of
      calcium/calmodulin-dependent kinases, also may be involved in the regulation of
      Pyk2 activity because its inhibitor KN62 attenuated Pyk2 phosphorylation during
      ischemia. Together with previous studies, these results indicate that calcium
      influx elicited by active NMDA receptors and L-VGCC triggers the Pyk2-Src
      signaling pathway mediated by PKC, which aggravates cerebral ischemia lesions
      through up-regulating the function of NMDA receptors after the onset of ischemia,
      and also could be regulated partly by CaM-dependent kinases like CaMKII.

PMID- 14732461
TI  - Acute intermittent nicotine treatment produces a reduction in the total number of
      FGF-2 immunoreactive astroglial cells in the substantia nigra of the rat: a
      stereological analysis.
AB  - To understand the morphological substrate of the nicotine effect on nigral FGF-2
      expression, a stereological analysis of FGF-2 immunoreactive neuronal and glial
      profiles has been performed in the substantia nigra of the rat after acute
      intermittent nicotine treatment. The major finding of this paper is the
      demonstration that this type of nicotine treatment produces a significant
      reduction in the total number of nuclear FGF-2 immunoreactive astroglial profiles
      in the substantia nigra. A parallel analysis of nigral FGF-1 and FGF-5
      immunoreactivities showed no effect of this type of nicotine treatment. The
      results may be explained by an inhibition of FGF-2 synthesis in a subpopulation
      of nigral astroglia by nicotinic receptor activation, favouring a reduction of
      astroglial neurotrophism in the substantia nigra.

PMID- 14732462
TI  - Leukoaraiosis and mobility decline: a high resolution magnetic resonance imaging
      study in older people with mild cognitive impairment.
AB  - Patterns of leukoaraiosis were analyzed on both T2-weighted fast fluid-attenuated
      inversion-recovery and 3D T1-weighted sequences in 23 community-dwelling older
      subjects with mild cognitive impairment. Mobility assessment had allowed their
      classification into higher and lower mobility groups (P<0.0001). Lower mobility
      appeared correlated with frontal subependymal lesions (P=0.0005). The absence of
      marked ventriculomegaly, any thick caps, deep white matter lesions curved along
      the ventricles bodies, large deep white matter lesions, deep grey matter
      leukoaraiosis was an hallmark of the higher mobility group (P<0.0001). High
      resolution MRI demonstrated regular patterns of the subependymal lesions and
      detected perivascular distribution in other forms of leukoaraiosis. It suggests
      that the underlying mechanism of mobility decline in the elderly may be
      impairment of cerebrospinal fluid dynamics with cerebral small vessel disease.

PMID- 14732463
TI  - Rhythmic training decreases latency-jitter of omission evoked potentials (OEPs)
      in humans.
AB  - In this study omission evoked potentials (OEPs) were studied in rhythmic experts
      (n=12) and non-musicians (n=12). Trains of auditory stimuli were presented.
      Trials (n=90) contained five omissions and started with a random number of beats,
      thus making every first omission unpredictable. Participants had to tap along
      with the first beat after the fifth omission (n=90), thus determining timing
      accuracy. Single-trial OEPs elicited by every first omission were obtained by
      means of wavelet denoising allowing determination of latency-jitter. Clear OEPs,
      consisting of a slow positive wave, maximal over Pz, were observed in response to
      unpredictable omissions. No group differences in OEPs amplitudes or latencies
      were observed. However, rhythmic experts showed less latency-jitter of both the
      OEPs positive wave and of behavioral responses compared with non-musicians.

PMID- 14732464
TI  - Polymorphisms of dopamine receptor and transporter genes and hallucinations in
      Parkinson's disease.
AB  - The authors conducted a case-control study of Parkinson's disease patients with
      and without visual hallucinations to investigate associations of the
      polymorphisms of the dopamine receptors D2 32806 C>T (Taq1A), D3 Ser9Gly and
      Msp1, D5 978T>C and dopamine transporter 3'-UTR 40 bp VNTR with visual
      hallucinations in Parkinson's disease. No significant differences were found
      between hallucinators and non-hallucinators in either the genotypic or allelic
      distributions. Our data suggest that the loci investigated here are not
      associated with the visual hallucinogenesis in Parkinson's disease.

PMID- 14732465
TI  - Postsynaptic density protein 95 mediates Ca2+/calmodulin-dependent protein kinase
      II-activated serine phosphorylation of neuronal nitric oxide synthase during
      brain ischemia in rat hippocampus.
AB  - Recent study has indicated that postsynaptic density protein 95 (PSD95) promotes
      Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated serine
      phosphorylation of neuronal nitric oxide synthase (nNOS). To investigate whether
      PSD95 is involved in the brain ischemia-induced enhancement of serine
      phosphorylation of nNOS by CaMKII in rat hippocampus, we examined the
      interactions among CaMKIIalpha, PSD95 and nNOS, and the effects of suppression of
      PSD95 expression on both the increased serine phosphorylation of nNOS and the
      interactions mentioned above by immunoprecipitation and immunoblotting. The
      following results were observed: (1) brain ischemia increased markedly the
      interactions of CaMKIIalpha and nNOS with PSD95. (2) Intracerebroventricular
      infusion of PSD95 antisense oligodeoxynucleotides, but not missense
      oligodeoxynucleotides or vehicle, not only significantly decreased the protein
      level of PSD95 but also attenuated the elevated serine phosphorylation of nNOS
      and the interactions among CaMKIIalpha, PSD95 and nNOS induced by 15 min
      ischemia. These data suggested that PSD95 is important for facilitating nNOS
      serine phosphorylation by CaMKII.

PMID- 14732466
TI  - Photoperiod affects the development of central neurotransmitter systems of
      tilapia, Oreochromis mossambicus.
AB  - The effects of photoperiod on the development of central neurotransmitters were
      investigated with tilapia, Oreochromis mossambicus. Zero-day-old (the hatching
      day) tilapia were raised in three different photoperiods (light/dark cycle):
      12/1, 24/0, and 0/24 h, respectively. On the 5th day, brain serotonin (5-HT),
      norepinephrine (NE), gamma-aminobutyric acid (GABA), and glutamate (Glu) contents
      were quantified by a high-performance liquid chromatograph with electrochemical
      detection. Similar experiments were performed on the 5-, 10-, 15-, 20-, and 25
      day-olds. These results showed that the photoperiod influenced both brain NE and
      GABA contents during its respective restricted period, before days 10
      posthatching. Brain 5-HT content was influenced, either facilitated or suppressed
      according to the developing stage, whereas, brain Glu content was not altered by
      the different photoperiod exposure throughout the present studies.

PMID- 14732467
TI  - The CCK2 agonist BC264 reverses freezing behavior habituation in PVG hooded rats
      on repeated exposures to a cat.
AB  - Our previous studies (NeuroReport 12 (2001) 2717) showed that PVG hooded and not
      Sprague-Dawley (SD) rats exhibit remarkable freezing behavior on exposure to a
      cat in the cat freezing test apparatus. In the present study, we further examined
      the differences between these two strains of rats in response to repeated daily
      exposure to a cat in the cat freezing test apparatus. Freezing behavior
      habituation was observed in both PVG hooded (days 5-7) and SD rats (days 3-7). A
      selective CCK(2) agonist (BC264, 0.3 microg/kg, i.p.) on day 8 reversed
      habituated freezing behavior and locomotor activity in PVG hooded rats, but not
      in SD rats. These results suggest that CCK2 receptors mediate habituation to an
      anxiety-inducing stimulus in PVG hooded rats and further suggest that
      differential expression of these CCK2 receptors underlies this strain difference.

PMID- 14732468
TI  - Functional contribution of medial premotor cortex to visuo-spatial transformation
      in humans.
AB  - This paper examines the functional contribution of medial premotor cortex, the
      supplementary motor area (SMA), to visuo-spatial transformation. Previous studies
      have found evidence of activation in SMA using 'mental rotation' tasks in which
      subjects make mirror-image judgements about simultaneously presented depth
      rotated novel forms. This manipulation induces potential confounds in the
      cognitive demands of the task in addition to spatial normalization processes. We
      clarify the role of SMA in visuo-spatial normalization using functional magnetic
      resonance imaging with a sequential mirror-image judgement task involving 2D
      image-plane rotated forms. The results show preferential activation of pre-SMA,
      as well as the ventrolateral prefrontal and parietal cortex during the visuo
      spatial transformation of mirror-image stimuli.

PMID- 14732469
TI  - Repeated electroconvulsive shock treatment increases the expression of A kinase
      anchoring proteins in the rat hippocampus.
AB  - Electroconvulsive shock (ECS) is widely used in the treatment of psychiatric
      disorders, but its mode of action remains largely unknown. Thus, this study was
      performed to examine the effect of repeated ECS treatment on the expression of A
      kinase anchoring proteins (AKAPs) in the brain. Rats were treated with ECS daily
      for 10 days. The expression of AKAP protein was analyzed by Western blotting, and
      AKAP mRNA by real-time quantitative RT-PCR. Repeated ECS treatment for 10 days
      resulted in increases in the levels of the protein and mRNA of AKAP150, yotiao,
      and ezrin in the rat hippocampus. Thus, repeated ECS treatment is suggested to
      increase the reactivity of glutamatergic synapses by increasing the expressions
      of the AKAPs, which can recruit protein kinase A to glutamate receptors.

PMID- 14732470
TI  - Expression of the mammalian homologue of vacuolar protein sorting 16 (Vps16p) in
      the mouse and rat brain.
AB  - Synaptic vesicle fusion events are essential for synaptic transmission. Membrane
      docking and fusion events are highly regulated processes requiring the
      participation of a large number of soluble N-ethylmaleimide-sensitive factors
      (SNAREs) and SNARE-interacting proteins. We report the neuronal expression of
      mammalian homologue of vacuolar protein sorting 16 (mVps16p) which exhibits a
      high homology to the yeast Vps16p, a component of Class C Vps. Western blot and
      immunohistochemical analyzes revealed that mVps16p is highly expressed in the
      various brain areas and developmental stages tested. The immunoreactivities of
      mVps16p colocalized with microtubule associated protein 2, but not glial
      fibrillary acidic protein. In the primary culture of cortical neurons, mVps16p
      immunoreactivities were observed in the cell body and the neuronal processes, and
      highly enriched in the axonal outgrowths.

PMID- 14732471
TI  - Protective effects of zinc chelation in traumatic brain injury correlate with
      upregulation of neuroprotective genes in rat brain.
AB  - Chelation of excessive neuronal zinc ameliorates zinc neurotoxicity and reduces
      subsequent neuronal injury. To clarify the molecular mechanisms of this
      neuroprotective effect, we used a focused cDNA array of stress-response genes
      with zinc chelation (calcium EDTA) in our rat model of fluid percussion brain
      injury at 2 h, 24 h, and 7 days after injury. In parallel experiments, we
      compared neuronal cell death in TUNEL-stained brain sections in traumatized rats
      with and without calcium EDTA treatment. Zinc chelation induced the expression of
      several neuroprotective genes; neuroprotective gene expression correlated with
      substantially decreased numbers of TUNEL-positive cells.

PMID- 14732472
TI  - Immune response to Abeta-peptides in peripheral blood from patients with
      Alzheimer's disease and control subjects.
AB  - To investigate the immune response to amyloid beta-peptide (Abeta: Abeta40 and
      Abeta42) in peripheral human blood, sera were obtained from 36 patients with
      Alzheimer's disease (AD) and 34 age-matched controls. ELISA assays were used to
      measure antibody concentrations to Abeta-peptides. T cell response was assessed
      using a lymphoproliferation assay. Both AD and control subjects had low and
      variable concentrations of antibodies against Abeta (predominantly IgG1). The
      mean antibody to Abeta concentrations did not differ between groups. No specific
      T cell response to Abeta-peptides was detected. Natural levels of antibodies to
      Abeta in peripheral blood are present in all human subjects and are unlikely to
      be useful in the identification of patients who would respond to potential AD
      immune therapy. Specific cellular immune responses to Abeta in human blood were
      not detected.

PMID- 14732473
TI  - Antioxidant propolis attenuates kainate-induced neurotoxicity via adenosine A1
      receptor modulation in the rat.
AB  - We examined the effects of the antioxidant propolis on seizures induced by kainic
      acid (KA). Sprague-Dawley rats received propolis (75 and 150 mg/kg, p.o.) five
      times at 12 h intervals. KA (10 mg/kg, i.p.) was injected 1 h after the last
      propolis treatment. Pretreatment with propolis significantly attenuated KA
      induced seizures and KA-induced increases in hippocampal AP-1 DNA binding
      activity in a dose-dependent manner. KA induced increases in the levels of
      malondialdehyde and protein carbonyl, and a decrease in the ratio of GSH/GSSG.
      These oxidative stresses and neuronal degenerations were significantly attenuated
      by pretreatment with propolis. The neuroprotective effects of propolis appeared
      to be counteracted by adenosine receptor antagonists [A1 antagonist, 8
      cyclopentyl-1,3-dimethylxanthine (25 or 50 microg/kg); A2A antagonist, 1,3,7
      trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg); and A2B antagonist,
      alloxazine (1.5 or 3.0 mg/kg)]. However, this counteraction was most pronounced
      in the presence of the A1 antagonist. Our results suggest that the protective
      effect of propolis against KA-induced neurotoxic oxidative damage is, at least in
      part, via adenosine A1 receptor modulation.

PMID- 14732474
TI  - Expression of chemokine receptors CXCR4, CCR2, CCR5 and CX3CR1 in neural
      progenitor cells isolated from the subventricular zone of the adult rat brain.
AB  - We have studied the expression of chemokine receptors CXCR4, CCR2, CCR5, and
      CX3CR1 at the mRNA and protein levels in adult neural progenitor cells (NPCs) in
      neurosphere cultures using RT-PCR and immunocytochemistry methods. NPCs were
      isolated from the subventricular zone of adult rat brain and propagated in vitro
      as neurospheres. The neurospheres showed immunoactivity of nestin, an
      intermediate filament marker for NPCs. NPCs in the neurosphere cultures
      differentiated into NeuN-, GFAP-, or GalC-positive cells in vitro. Using cultured
      cortical microglial cells as positive control, we demonstrated the mRNA
      expression of CXCR4, CCR2, CCR5, and CX3CR1 in neurospheres by RT-PCR. Double
      immunofluorescent staining further confirmed the co-localization of nestin with
      either CXCR4, CCR2, CCR5, or CX3CR1 on neurospheres. These results suggest that
      adult NPCs in the neurosphere cultures express chemokine receptors CXCR4, CCR2,
      CCR5, and CX3CR1.

PMID- 14732475
TI  - Association of apolipoprotein A5 variants with LDL particle size and triglyceride
      in Japanese Americans.
AB  - A new apolipoprotein (apo) gene, APOA5, was recently identified on chromosome
      11q23, and common variants in the gene have been associated with plasma
      triglyceride (TG) levels in several studies. The purpose of the present study was
      to examine the association of five single nucleotide polymorphisms (SNPs) and
      haplotypes in the APOA5 gene with low-density lipoprotein (LDL) particle size
      using a community-based sample of Japanese American families, including examining
      whether the associations with LDL size are independent of, or primarily
      reflecting, TG levels. Genetic association analyses were performed using 154
      unrelated individuals, quantitative transmission disequilibrium tests (TDT) in
      238 nuclear families, a sample of 24 hypertriglyceridemic subjects with matched,
      normotriglyceridemic controls, and using haplotype analyses. There was a high
      degree of allelic association between several of the SNPs, with complete linkage
      disequilibrium (LD) between -1131C>T and the -3A>G SNP which alters a potential
      Kozak sequence. All approaches demonstrated associations between the -3A>G APOA5
      variant and both decreased LDL size and increased TG levels. The frequency of the
      rare allele was higher than reported for Caucasian, Hispanic, and African
      Americans, but similar to that in Japan and China. Therefore, the haplotype
      containing the -1131C and -3G variants, and possibly specifically the -3A>G SNP
      in APOA5, may be a major genetic determinant of LDL particle size and TG levels
      among ethnic Asians.

PMID- 14732476
TI  - Role of lipid interactions in autoimmune demyelination.
AB  - A morphological transformation involving loss of adhesion between myelin lamellae
      and formation of myelin vesicles has been described as a mechanism for
      demyelination in multiple sclerosis and marmoset experimental allergic
      encephalomyelitis (EAE). Although protein interactions are involved in
      maintaining normal myelin structure, we describe here how lipids contribute to
      myelin stability and how lipid changes in EAE, including increases in lipid
      polyunsaturation and negatively charged phosphatidylserine (PS), promote
      demyelination. Three physico-chemical techniques were used to identify these
      changes: (1) Langmuir monolayer isotherms indicated that EAE white matter lipids
      were significantly more "expanded" (fluid) than controls. (2) NMR spectroscopy
      indicated that EAE myelin lipids were more polyunsaturated than controls. (3)
      High-performance liquid chromatography (HPLC) with an evaporative light
      scattering detector indicated increased PS in EAE compared to controls, while
      sphingomyelin (SM), sulfatides and phosphatidylcholine (PC) were decreased. We
      present a physical model considering electrostatic, van der Waals and undulation
      forces to quantify the effect of these changes on myelin adhesion at the
      extracellular interface. Taken together, the isotherm, NMR, HPLC and modeling
      results support a mechanism for autoimmune demyelination whereby the composition
      of myelin lipids is altered in a manner that increases myelin fluidity, decreases
      myelin adhesion, increases membrane curvature, and promotes vesiculation.

PMID- 14732477
TI  - Interaction of regular exercise and chronic nitroglycerin treatment on blood
      pressure and rat aortic antioxidants.
AB  - Many cardiac patients undergo exercise conditioning with or without medication.
      Therefore, we investigated the interaction of exercise training and chronic
      nitroglycerin treatment on blood pressure (BP), aortic nitric oxide (NO),
      oxidants and antioxidants in rats. Fisher 344 rats were divided into four groups
      and treated as follows: (1) sedentary control, (2) exercise training (ET) for 8
      weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) ET+nitroglycerin.
      BP was monitored with tail-cuff method. The animals were sacrificed 24 h after
      the last treatments and thoracic aorta was isolated and analyzed. Exercise
      training on treadmill for 8 weeks significantly increased respiratory exchange
      ratio (RER), aortic NO levels, and endothelial nitric oxide synthase (eNOS)
      protein expression. Training significantly enhanced aortic glutathione (GSH),
      reduced to oxidized glutathione (GSH/GSSG) ratio, copper/zinc-superoxide
      dismutase (CuZn-SOD), Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px)
      glutathione disulfide reductase (GR) activities and protein expressions. Training
      significantly depleted aortic malondialdehyde (MDA) and protein carbonyls without
      change in BP. Nitroglycerin administration for 8 weeks significantly increased
      aortic NO levels and eNOS protein expression. Nitroglycerin significantly
      enhanced aortic Mn-SOD, CAT, GR and glutathione-S-transferase (GST) activities
      and protein expressions with decreased MDA levels, protein carbonyls and BP.
      Interaction of training and nitroglycerin treatment significantly increased
      aortic NO levels, eNOS protein expression, GSH/GSSG ratio, antioxidant enzymes
      and normalized BP. The data suggest that the interaction of training and
      nitroglycerin maintained BP by up-regulating the aortic NO and antioxidants and
      reducing the oxidative stress in rats.

PMID- 14732478
TI  - Evidence that oxidative stress is increased in patients with X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of peroxisomal
      metabolism biochemically characterized by the accumulation of very long chain
      fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) and tetracosanoic
      acid (C24:0) in different tissues and in biological fluids. The disease is
      clinically characterized by central and peripheral demyelination and adrenal
      insufficiency, which is closely related to the increased concentrations of these
      fatty acids. However, the mechanisms underlying the brain damage in X-ALD are
      poorly known. Considering that free radical generation is involved in various
      neurodegenerative disorders, like Parkinson disease, multiple sclerosis and
      Alzheimer's disease, in the present study we evaluated various oxidative stress
      parameters, namely chemiluminescence, thiobarbituric acid reactive species (TBA
      RS), total radical-trapping antioxidant potential (TRAP), and total antioxidant
      reactivity (TAR) in plasma of X-ALD patients, as well as the activities of the
      antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione
      peroxidase (GPx) in erythrocytes and fibroblasts from these patients. It was
      verified a significant increase of plasma chemiluminescence and TBA-RS,
      reflecting induction of lipid peroxidation, as well as a decrease of plasma TAR,
      indicating a deficient capacity to rapidly handle an increase of reactive
      species. We also observed a significant increase of erythrocytes GPx activity and
      of catalase and SOD activities in fibroblasts from the patients studied. It is
      therefore proposed that oxidative stress may be involved in pathophysiology of X
      ALD.

PMID- 14732479
TI  - Copper-mediated LDL oxidation by homocysteine and related compounds depends
      largely on copper ligation.
AB  - Oxidation of low-density lipoprotein (LDL) is thought to be a major factor in the
      pathophysiology of atherosclerosis. Elevated plasma homocysteine is an accepted
      risk factor for atherosclerosis, and may act through LDL oxidation, although this
      is controversial. In this study, homocysteine at physiological concentrations is
      shown to act as a pro-oxidant for three stages of copper-mediated LDL oxidation
      (initiation, conjugated diene formation and aldehyde formation), whereas at high
      concentration, it acts as an antioxidant. The affinity for copper of homocysteine
      and related copper ligands homocysteine, cystathionine and djenkolate was
      measured, showing that at high concentrations (100 microM) under our assay
      conditions, they bind essentially all of the copper present. This is used to
      rationalise the behaviour of these ligands, which stimulate LDL oxidation at low
      concentration but generally inhibit it at high concentration. Albumin strongly
      reduced the effect of homocystine on lag time for LDL oxidation, suggesting that
      the effects of homocystine are due to copper binding. In contrast, copper binding
      does not fully explain the pro-oxidant behaviour of low concentrations of
      homocysteine towards LDL, which appears in part at least to be due to stimulation
      of free radical production. The likely role of homocysteine in LDL oxidation in
      vivo is discussed in the light of these results.

PMID- 14732480
TI  - Cell protection, resistance and invasiveness of two malignant mesotheliomas as
      assessed by 10K-microarray.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive serosal tumor, strongly
      associated with former exposure to asbestos fibers and for which there is
      currently no effective treatment available. In human, MPM is characterized by a
      high local invasiveness, poor prognosis and therapeutic outcomes. In order to
      assess molecular changes that specify this phenotype, we performed a global gene
      expression profiling of human MPM. Using a 10,000-element microarray, we analyzed
      mRNA relative gene expression levels by comparing a mesothelioma cell line to
      either a pleural cell line or tumor specimens. To analyze these gene expression
      data, we used various bioinformatics softwares. Hierarchical clustering methods
      were used to group genes and samples with similar expression in an unsupervised
      mode. Genes of known function were further sorted by enzyme, function and pathway
      clusters using a supervised software (IncyteGenomics). Taken together, these data
      defined a molecular fingerprint of human MPM with more than 700 up- or down
      regulated genes related to several traits of the malignant phenotype, specially
      associated with MPM invasiveness, protection and resistance to anticancer
      defenses. This portrait is meaningful in disease classification and management,
      and relevant in finding new specific markers of MPM. These molecular markers
      should improve the accuracy of mesothelioma diagnosis, prognosis and therapy.

PMID- 14732481
TI  - Hypobetalipoproteinemia with an apparently recessive inheritance due to a "de
      novo" mutation of apolipoprotein B.
AB  - Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder either linked
      or not linked to apolipoprotein (apo) B gene. Abetalipoproteinemia (ABL) is a
      recessive disorder due to mutations of microsomal triglyceride transfer protein
      (MTP) gene. We investigated a patient with apparently recessive
      hypobetalipoproteinemia consistent with symptomatic heterozygous FHBL or a "mild"
      form of ABL. The proband had fatty liver associated with LDL-cholesterol (LDL-C)
      and apo B levels <5th percentile but no truncated apo B forms detectable in
      plasma. MTP gene sequence revealed that he was a carrier of the I128T
      polymorphism and an unreported amino acid substitution (V168I) unlikely to be the
      cause of hypobetalipoproteinemia. Apo B gene sequence showed that he was
      heterozygous for two single base substitutions in exon 9 and 22 resulting in a
      nonsense (Q294X) and a missense (R1101H) mutation, respectively. Neither of his
      parents carried the Q294X; his father and paternal grandmother carried the R1101H
      mutation. Analysis of polymorphic genetic markers excluded non-paternity. In
      conclusion, the proband has a "de novo" mutation of apo B gene resulting in a
      short truncated apo B form (apo B-6.46). Sporadic cases of FHBL with an
      apparently recessive transmission may be caused by "de novo" mutations of apo B
      gene.

PMID- 14732482
TI  - Characterisation of 11 beta-hydroxysteroid dehydrogenases in feline kidney and
      liver.
AB  - 11 Beta-hydroxysteroid dehydrogenases type 1 and 2 (11 beta-HSD1 and 11 beta
      HSD2) are microsomal enzymes responsible for the interconversion of cortisol into
      the inactive form cortisone and vice versa. 11 beta-HSD1 is mainly present in the
      liver, and has predominantly reductase activity although its function has not yet
      been elucidated. 11 beta-HSD2, present in mineralocorticoid target tissues such
      as the kidney, converts cortisol into cortisone. Reduced activity due to
      inhibition or mutations of 11 beta-HSD2 leads to hypertension and hypokalemia
      resulting in the Apparent Mineralocorticoid Excess Syndrome (AMES). Like humans,
      cats are highly susceptible for hypertension. As large species differences exist
      with respect to the kinetic parameters (K(m) and V(max)) and amino acid sequences
      of both enzymes, we determined these characteristics in the cat. Both enzyme
      types were found in the kidneys. 11 beta-HSD1 in the feline kidney showed
      bidirectional activity with predominantly dehydrogenase activity (dehydrogenase:
      K(m) 1959+/-797 nM, V(max) 766+/-88 pmol/mg*min; reductase: K(m) 778+/-136 nM,
      V(max) 112+/-4 pmol/mg*min). 11 beta-HSD2 represents a unidirectional
      dehydrogenase with a higher substrate affinity (K(m) 184+/-24 nM, V(max) 74+/-3
      pmol/mg*min). In the liver, only 11 beta-HSD1 is detected exerting reductase
      activity (K(m) 10462 nM, V(max) 840 pmol/mg*min). Sequence analysis of conserved
      parts of 11 beta-HSD1 and 11 beta-HSD2 revealed the highest homology of the
      feline enzymes with the correspondent enzymes found in man. This suggests that
      the cat may serve as a suitable model species for studies directed to the
      pathogenesis and treatment of human diseases like AMES and hypertension.

PMID- 14732483
TI  - Identification of the "missing domain" of the rat copper-transporting ATPase,
      atp7b: insight into the structural and metal binding characteristics of its N
      terminal copper-binding domain.
AB  - Wilson disease is an autosomal disorder of copper transport caused by mutations
      in the ATP7B gene encoding a copper-transporting P-type ATPase. The Long Evans
      Cinnamon (LEC) rat is an established animal model for Wilson disease. We have
      used structural homology modelling of the N-terminal copper-binding region of the
      rat atp7b protein (rCBD) to reveal the presence of a domain, the fourth domain
      (rD4), which was previously thought to be missing from rCBD. Although the CXXC
      motif is absent from rD4, the overall fold is preserved. Using a wide range of
      techniques, rCBD is shown to undergo metal-induced secondary and tertiary
      structural changes similar to WCBD. Competition 65Zn(II)-blot experiments with
      rCBD demonstrate a binding cooperativity unique to Cu(I). Far-UV circular
      dichroism (CD) spectra suggest significant secondary structural transformation
      occurring when 2-3 molar equivalents of Cu(I) is added. Near-UV CD spectra, which
      indicate tertiary structural transformations, show a proportional decrease in
      rCBD disulfide bonds upon the incremental addition of Cu(I), and a maximum 5:1
      Cu(I) to protein ratio. The similarity of these results to those obtained for the
      Wilson disease N-terminal copper-binding region (WCBD), which has six copper
      binding domains, suggests that the metal-dependent conformational changes
      observed in both proteins may be largely determined by the protein-protein
      interactions taking place between the heavy metal-associated (HMA) domains, and
      remain largely unaffected by the absence of one of the six CXXC copper-binding
      sites.

PMID- 14732484
TI  - Leptin and the control of respiratory gene expression in muscle.
AB  - Leptin plays a central role in the regulation of fatty acid homeostasis,
      promoting lipid storage in adipose tissue and fatty acid oxidation in peripheral
      tissues. Loss of leptin signaling leads to accumulation of lipids in muscle and
      loss of insulin sensitivity secondary to obesity. In this study, we examined the
      direct and indirect effects of leptin signaling on mitochondrial enzymes
      including those essential for peripheral fatty acid oxidation. We assessed the
      impact of leptin using the JCR:LA-cp rat, which lacks functional leptin
      receptors. The activities of marker mitochondrial enzymes citrate synthase (CS)
      and cytochrome oxidase (COX) were similar between wild-type (+/?) and corpulent
      (cp/cp) rats. In contrast, several tissues showed variations in the fatty acid
      oxidizing enzymes carnitine palmitoyltransferase II (CPT II), long-chain acyl-CoA
      dehydrogenase (LCAD) and 3-hydroxyacyl-CoA dehydrogenase (HOAD). It was not clear
      if these changes were due to loss of leptin signaling or to insulin
      insensitivity. Consequently, we examined the effects of leptin on cultured
      C(2)C(12) and Sol8 cells. Leptin (3 days at 0, 0.2, or 2.0 nM) had no direct
      effect on the activities of CS, COX, or fatty acid oxidizing enzymes. Leptin
      treatment did not affect luciferase-based reporter genes under the control of
      transcription factors involved in mitochondrial biogenesis (nuclear respiratory
      factor-1 (NRF-1), nuclear respiratory factor-2 (NRF-2)) or fatty acid enzyme
      expression (peroxisome proliferator-activated receptors (PPARs)). These studies
      suggest that leptin exerts only indirect effects on mitochondrial gene expression
      in muscle, possibly arising from insulin resistance.

PMID- 14732485
TI  - Changes in the activities and gene expressions of poly(ADP-ribose)
      glycohydrolases during the differentiation of human promyelocytic leukemia cell
      line HL-60.
AB  - The metabolism of poly(ADP-ribose) is known to play important roles in the
      nuclear function of the mammalian cells. In this study, changes in the activities
      and gene expressions of poly(ADP-ribose) glycohydrolases (PARG) in HL-60 cells
      treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or a PARG inhibitor,
      tannic acid, were investigated. Nuclear PARG activities of HL-60 cells treated
      with TPA were reduced to 30-40% of the activity in untreated cells at 24 h, while
      PARG activities in the cytoplasm remained unchanged. The transient decrease in
      the nuclear PARG activity by TPA treatment was accompanied by differentiation as
      measured by the nitroblue tetrazolium (NBT) reducing activity and adhesion to the
      culture dishes. In the presence of H7, an inhibitor of protein kinase C (PKC),
      both the decrease in nuclear PARG activity and the induction of differentiation
      by TPA treatment were suppressed. On the other hand, treatment with tannic acid
      caused the nuclear PARG activity to decrease continuously while the NBT reducing
      activity increased, but no morphological differentiation to macrophage-like cells
      was apparent. In order to analyze PARG gene expression, we isolated the human
      PARG cDNA by the RT-PCR technique. RT-PCR analysis revealed that TPA treatment
      leads to a reduction in the PARG gene expression prior to the phenotypic
      expression of macrophage-like cell differentiation, which was diminished by the
      presence of H7. Also, PARG gene expression was reduced by tannic acid treatment.
      These results provide the first evidence that a transient decrease in nuclear
      PARG activity is important for the onset of differentiation of HL-60 cells to
      macrophage-like cells.

PMID- 14732486
TI  - The sperm-specific proteins of the edible oyster (European flat oyster (Ostrea
      edulis)) are products of proteolytic processing.
AB  - Extraction of sperm proteins from the bivalve mollusc Ostrea edulis shows them to
      contain a normal complement of core histones, together with three sperm-specific
      proteins, OE1 and OE2, plus the shorter OE3, which shows substantial
      microheterogeneity. OE1 and OE2 have a very similar amino acid composition,
      cyanogen bromide (CNBr) cleavage yields products of identical size and possesses
      a trypsin-resistant core peptide, together indicating that they are closely
      homologous histone H1-like proteins. Western blotting shows that OE1 and OE2 are
      closely related to the histone H1-like protein PL-II* of Mytilus trossulus. The
      amino acid composition of OE3 shows it to be a protamine-like PL-IV type protein.
      Edman degradation of a CNBr peptide from OE2 gave the sequence
      (M)KAAFAKGLKSGALVRPKGS-which has 85% identity to a sequence located towards the C
      terminal end of the globular domain of the PL-II* protein of M. trossulus. An O.
      edulis sperm cDNA library yielded a clone of 428 bp. A genomic clone including an
      open reading frame (ORF) of 750 bp was isolated by PCR amplification from genomic
      DNA. Hypothetical translation showed the ORF to encode OE1 (or OE2) immediately
      followed by OE3, separated by a proteolytic processing site. This arrangement (a
      two-protein ORF) is also found in M. trossulus and Ensis minor.

PMID- 14732487
TI  - Genomic investigation of the system for selenocysteine incorporation in the
      bacterial domain.
AB  - The elucidation of nearly 100 bacterial genomes has made it possible to
      categorize them into two groups, according to the presence or absence of a
      selenocysteine (Sec) tRNA. In the group with the tRNA, a Sec incorporation system
      like that of Escherichia coli would be expected. However, for the other group,
      the following question has been left unsolved. Is it reasonable to assume that
      bacteria without the tRNA lack the entire Sec system, and do such bacteria exist
      commonly? To explore it experimentally, we chose Bacillus subtilis, a
      representative eubacterium for which a Sec tRNA has not been found. First, we
      reviewed the genome to search for the tRNA gene. Second, we examined the possible
      expression of an unknown tRNA. Third, we examined Sec-related enzymes and
      proteins in B. subtilis cell extracts. Fourth, the B. subtilis and E. coli seryl
      tRNA synthetases were expressed, and the specificity was analyzed. Consequently,
      all of the data showed negative results about the existence of the Sec system in
      B. subtilis. Additionally, we discuss the possibility of predicting the existence
      or absence of the system in each bacterial organism by using the Sec tRNA and
      seryl-tRNA synthetase as indicators.

PMID- 14732488
TI  - Characterization of the zebrafish vascular endothelial growth factor A gene:
      comparison with vegf-A genes in mammals and Fugu.
AB  - Vascular endothelial growth factor (VEGF-A) is a key angiogenic growth factor
      which regulates vertebrate embryonic vascularization, adult physiology such as
      wound healing and reproduction as well as many human diseases. To understand the
      evolution and regulation of this gene in vertebrates, we have isolated and
      characterized the zebrafish vegf-A gene and compared it with VEGF-A genes of
      human, mouse as well as an in silico isolated VEGF-A homologue from pufferfish.
      Our results indicate that the zebrafish vegf-A gene is organized similarly to
      mammalian and Fugu VEGF-A genes, with eight exons interrupted by seven introns.
      However, zebrafish vegf-A introns are generally larger than mammalian introns
      while Fugu VEGF-A introns are much smaller. Furthermore, zebrafish exon 6 (z6)
      has a unique sequence while Fugu's exon 6 is highly homologous to the mammalian
      counterparts. Alternative splicing generates multiple vegf-A mRNA isoforms in
      zebrafish with Vegf(121) as the dominant isoform in adult and Vegf(165) as the
      dominant isoform in early embryos. The exon z6 containing isoform Vegf(12345z678)
      is only detected in heart, muscle, and early embryos while another isoform Vegf
      A(1234577)(a)(8) is only detected in heart. Furthermore, no conserved 5' flanking
      sequences between zebrafish and Fugu were observed while numerous conserved
      regions exist between human and mouse in this area. These results suggest both
      conserved and diverged functions of VEGF-A from fish to mammals since the
      separation of these two groups from their common ancestor about 450 million years
      ago and a diverged regulation of this gene since the separation of zebrafish from
      Fugu. These data will be valuable for future studies of VEGF-A gene regulation
      and function in different vertebrates.

PMID- 14732489
TI  - Identification of a novel enhancer of brain expression near the apoE gene cluster
      by comparative genomics.
AB  - Comparative analysis of the human and mouse genomic sequences downstream of the
      apolipoprotein E gene (APOE) revealed a highly conserved element with previously
      undefined function. In reporter gene transfection studies, this element which is
      located approximately 42 kb distal to APOE was found to have silencer activity in
      a subset of cell lines examined. Analysis of transgenic mice containing a fusion
      construct linking this distal 631 bp conserved element to a reporter gene
      comprised of the human APOE gene with its proximal promoter resulted in robust
      brain expression of the transgenic human apoE mRNA in three independent
      transgenic lines, supporting the identification of a novel brain controlling
      region (BCR). Further studies using immunohistochemistry revealed widespread
      human apoE localization throughout the brains of the BCR-apoE transgenic mice
      with prominent expression in the cortex and diencephalon. In addition, double
      label immunofluorescence performed on brain sections and cultures of primary
      cortical cells localized human apoE protein to cortical neurons and microglia.
      These studies demonstrate that comparative sequence analysis is a successful
      strategy to predict candidate regulatory regions in vivo, although they do not
      imply that this element controls apoE expression physiologically.

PMID- 14732490
TI  - R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the
      dorsal neural tube and affected in Wnts mutants.
AB  - We identified a novel gene, which encodes a 265-amino-acid sequence with a
      thrombospondin (TSP) type 1 motif. Unlike the other secretory proteins of the TSP
      family, this gene encodes no apparent secretion cleavage site, but has a putative
      nuclear localization signal. Northern blot analysis showed transient expression
      in the central nervous system (CNS) during development. In situ hybridization
      showed its expression in the dorsal part of the neural tube on 10 and 12 dpc,
      especially in the boundary region between roof plate and neuroepithelium. This
      expression was enhanced in the rostral part. The signals were observed in other
      tissues such as truncal region neighboring forelimbs and mesenchymal tissues
      around the nasal cavity. We named this gene R-spondin (roof plate-specific
      spondin). Transfection of an epitope-tagged R-spondin into COS7 and 293 cells
      showed its localization in nuclei and medium, suggesting that R-spondin may
      become secretory or nuclear protein by some processing, while most of other
      proteins with TSP type 1 domain are secretory proteins. The expression of R
      spondin was reduced in Wnt-1/3a double knockout mouse. R-spondin might be a novel
      marker of the boundary between the roof plate and neuroepithelium and may
      contribute to the development of dorsal neural tube under the regulation of Wnts.

PMID- 14732491
TI  - Up-regulation of fatty acid-binding proteins during hibernation in the little
      brown bat, Myotis lucifugus.
AB  - Hibernating animals rely primarily on lipids throughout winter as their primary
      fuel source, thus it is hypothesized that an increase in genes and proteins
      relating to lipid transport will increase accordingly. The cloning and expression
      of heart type fatty acid-binding protein (h-fabp) from a mammalian hibernator,
      the little brown bat Myotis lucifugus, is presented. Northern blot analysis
      revealed that transcript levels of h-fabp were significantly higher during
      hibernation in brown adipose tissue and skeletal muscle compared with levels in
      euthermic bats. Similarly, heterologous probing with rat adipose type a-fabp
      found 3.9-fold higher levels of a-fabp transcripts in brown adipose from
      hibernating animals. Levels of A- and H-FABP protein were quantified in tissues
      of euthermic versus hibernating animals by Western blotting. A-FABP was 4-fold
      higher in brown adipose of hibernating, compared with euthermic bats, whereas H
      FABP was significantly higher in hibernator brown adipose, heart and skeletal
      muscle. The present work implicates FABPs as important elements related to the
      hibernating state in mammals; alterations in gene and protein expression along
      with amino acid substitutions are shown. These likely contribute to optimizing
      the function of FABPs at the low body temperatures (near 0 degrees C) experienced
      in the hibernating state.

PMID- 14732492
TI  - GltX from Clostridium saccharobutylicum NCP262: glutamate synthase or
      oxidoreductase?
AB  - A full-length gene encoding a homologue of the small subunit of the glutamate
      synthase (GOGAT) enzyme was isolated from the anaerobic bacterium, Clostridium
      saccharobutylicum NCP262, which has been used extensively for the commercial
      production of solvents. Using a screening system designed to isolate genes
      involved in electron transport, plasmid pMET13C1 was isolated. Analysis of this
      plasmid identified a gene (1245 bp) with a predicted approximately 46-kDa
      product, which was associated with reductive activation of the pro-drug
      metronidazole. The deduced 414-amino-acid sequence was not typical of electron
      transport proteins, but rather shared striking homology to the small (beta)
      subunit of the GOGAT enzyme and other beta subunit-like polypeptides, and was
      thus designated gltX. Although all the functional domains typical of GOGAT beta
      subunits were conserved in this GltX protein, certain sequence features were not
      conserved. Furthermore, it was independently transcribed, did not lie adjacent to
      a GOGAT large subunit (alpha) domain, and its expression was not regulated by
      nitrogen conditions. These results provide additional support for current
      theories on the evolutionary relationships of GOGAT beta subunit domains in
      bacteria, and suggest that GltX belongs to a more general family of
      oxidoreductases, which is used in a context other than glutamate biosynthesis to
      transfer electrons to a currently unknown protein domain.

PMID- 14732493
TI  - Downregulation of genes involved in DNA repair and differential expression of
      transcription regulators and phosphatases precede IgM-induced apoptosis in the
      Burkitt's lymphoma cell line BL60-2.
AB  - Apoptosis of lymphocytes recognizing self-antigens is an essential mechanism to
      protect the organism against autoimmune diseases. Programmed cell death of
      susceptible B cells occurs in response to surface IgM cross-linking mediated by
      self-antigens. This effect can be mimicked in the Burkitt's lymphoma line BL60-2
      by addition of anti-IgM antibodies. In order to identify genes with differential
      expression in response to the apoptotic stimulus, total RNA prepared from BL60-2
      cells before and at different points in time after IgM cross-linking was used for
      Atlas arrays, high-density oligonucleotide microarrays (GeneChip arrays,
      Affymetrix) and in RNase protection assays (RPA). One of our major observations
      was the downregulation of six genes involved in the ligation of DNA strand
      breaks, like DNA ligases and DNA-PK, indicating a shutdown of DNA repair
      mechanisms in apoptotic cells. In addition, we found changes on mRNA level for
      several transcription regulators, including early growth response genes 1 and 2,
      TAFII30 and topoisomerase I. Furthermore, we show accumulation of mRNA for the
      phosphatases CD45 and DUSP5 in anti-IgM stimulated BL60-2 cells. Our data provide
      a basis for further analysis of the differentially expressed genes and their
      roles in IgM-induced B cell death as well as in apoptosis in other cellular
      systems.

PMID- 14732494
TI  - NEUROD1 acts in vitro as an upstream regulator of NEUROD2 in trophoblast cells.
AB  - The basic helix-loop-helix (bHLH) transcription factors NEUROD1, NEUROD2 and ATH2
      are expressed during first trimester human placental development. We determined
      the transactivation potential of each of these factors in trophoblasts by
      measuring changes in the endogenous gene activity using absolute quantification
      by real-time quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) after transient transfection. In these assays, NEUROD1 was found to
      transiently transactivate NEUROD2 in trophoblast cells. Promotor truncation
      assays, using luciferase constructs, showed the presence of two domains in the
      NEUROD2 promotor, which showed increased activity after NeuroD1 transfection.
      Each of these NeuroD1-responsive domains contains an E-box sequence. The NEUROD2
      transactivation data fit with the spatial expression pattern of NEUROD1 and
      NEUROD2, since they are expressed in endovascular trophoblasts. This expression
      pattern, as well as the present transactivation results, might suggest the
      presence of a NEUROD differentiation cascade during first trimester human
      placental development.

PMID- 14732495
TI  - Human leukocyte elastase gene expression is regulated by PU.1 in conjunction with
      closely associated cytidine-rich and Myb binding sites.
AB  - Leukocyte elastase (LE) degrades connective tissue, is involved in the
      inflammatory process and implicated in cyclic and congenital neutropenia. The
      human LE gene is within a serine proteinase locus on chromosome 19 pter13.3. Our
      observations demonstrate that LE gene expression is regulated by PU.1, a cytidine
      rich and a Myb binding site. The LE promoter has two cytidine-rich sites at -158
      and -185. The -158 is the active site and it is closest to the PU.1 site.
      Proximity is essential to activity since separation of the -158 and PU.1 sites by
      a 20-base pair oligonucleotide reduced promoter activity by 50%. This suggests
      physical interaction between the transcription proteins binding to the PU.1 and 
      158 sites. The nuclear protein that binds the -158 site is present in B and T
      lymphocytes and an erythroleukemia cell line in addition to being abundant in the
      promyelocytic stage of neutrophil maturation when the LE gene is expressed. The
      protein binding to the -158 site is absent or expressed at low levels in non
      hematopoietic cell lines. We have identified the transcription factors essential
      for human LE gene expression. Comparison with the mouse LE gene shows
      similarities and differences.

PMID- 14732496
TI  - Cloning and molecular characterization of the atp operon encoding for the F1F0
      ATP synthase from a thermoalkaliphilic Bacillus sp. strain TA2.A1.
AB  - The genes encoding the subunits for the F(1)F(0)-ATP synthase from Bacillus sp.
      strain TA2.A1 were cloned as three overlapping fragments and sequenced. The nine
      genes were organized in an operon with the gene order atpIBEFHAGDC encoding the
      i, a, c, b, delta, alpha, gamma, beta, and epsilon subunits, respectively.
      Northern blot analysis showed a maximum transcript of approximately 7.2 kb, which
      corresponds to the size of the atp operon and demonstrated that the nine genes
      are transcribed as a single polycistronic message. The alkaliphilic-specific
      residues Lys(218) and Gly(245) were conserved in subunit a of strain TA2.A1.
      Analysis of the C-terminal domain of the epsilon subunit showed several clusters
      of basic residues which are predicted to form a strong electrostatic interaction
      with the DELSDED motif in the beta subunit from strain TA2.A1, and may explain
      the blockage of this enzyme in the ATP hydrolysis direction.

PMID- 14732497
TI  - Abstracts of the Annual meeting of the Society for Adolescent Medicine. March 24
      27, 2004. St. Louis, Missouri, USA.

PMID- 14732588
TI  - Laser-assisted microdissection: methods for the molecular analysis of psychiatric
      disorders at a cellular resolution.
AB  - Gene expression arrays and proteomics together provide a great opportunity to
      reveal the molecular pathophysiology of psychiatric disorders; however, their
      potential will not be realized unless due attention is paid to the cellular
      heterogeneity of the brain and the likely differential neuropathological
      involvement of specific neuronal and glial cell types. Hence, methods are needed
      which can procure homogeneous populations of cells as a source of messenger RNA,
      protein, or DNA. Laser-assisted microdissection techniques provide such a tool.
      Here we briefly discuss the principles, applications, and limitations of laser
      assisted microdissection in psychiatric research.

PMID- 14732589
TI  - NOTCH4 gene haplotype is associated with schizophrenia in African Americans.
AB  - BACKGROUND: The goal of this study was to investigate the relationship between
      the NOTCH4 gene and schizophrenia in African American (AA) and European American
      (EA) subjects. METHODS: Two single nucleotide polymorphisms (SNPs) at the NOTCH4
      locus were genotyped in 123 AA schizophrenia patients, 223 EA schizophrenia
      patients, 85 AA healthy control subjects, and 211 EA healthy control subjects.
      The specific markers studied were -1725T/G and -25T/C. Comparisons of allele and
      haplotype frequencies between patients and control subjects were performed with
      the chi-square test, the Fisher's Exact Test, and CLUMP software. Linkage
      disequilibrium (LD) between these two SNPs was calculated with the 3LOCUS
      program. RESULTS: The haplotype -1725G/-25T associates to schizophrenia in AA
      subjects (p =.0008), but not in EA subjects. Alleles -1725G and allele -25T are
      in positive LD both in AAs and EAs. Allele and haplotype frequencies differ
      significantly between AAs and EAs. CONCLUSIONS: The haplotype -1725G/-25T at the
      NOTCH4 locus, which results from SNPs of NOTCH4 that are in LD, may increase
      susceptibility to schizophrenia in AAs. Any effect of this locus on risk for
      schizophrenia is population-specific.

PMID- 14732590
TI  - A rare polymorphism affects a mitogen-activated protein kinase site in synapsin
      III: possible relationship to schizophrenia.
AB  - BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to
      chromosome 22q12-13, a region suggested to be linked to schizophrenia. To
      determine if synapsin III plays a role in this disease, we searched for
      polymorphisms in this gene in patients with schizophrenia and controls. METHODS:
      The synapsin III gene was initially sequenced from 10 individuals with
      schizophrenia to identify polymorphisms. Association analysis was then performed
      using 118 individuals with schizophrenia and 330 population controls. Synapsin
      III expression was studied by immunoblot analyses, and phosphorylation sites were
      mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with
      phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in
      the synapsin III gene and appeared more frequently in individuals with
      schizophrenia than in controls (p =.0048). The site affected by the polymorphism,
      Ser470, was determined to be a substrate for mitogen-activated protein kinase, a
      downstream effector of neurotrophin action. Phosphorylation at Ser470 was
      increased during neonatal development and in response to neurotrophin-3 in
      cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an
      association of a rare polymorphism in synapsin III with schizophrenia, but
      further studies will be required to clarify its role in this disease.

PMID- 14732591
TI  - Gray and white matter volume abnormalities in monozygotic and same-gender
      dizygotic twins discordant for schizophrenia.
AB  - BACKGROUND: Whole brain tissue volume decreases in schizophrenia have been
      related to both genetic risk factors and disease-related (possibly nongenetic)
      factors; however, whether genetic and environmental risk factors in the brains of
      patients with schizophrenia are differentially reflected in gray or white matter
      volume change is not known. METHODS: Magnetic resonance imaging (1.5 T) brain
      scans of 11 monozygotic and 11 same-gender dizygotic twin pairs discordant for
      schizophrenia were acquired and compared with 11 monozygotic and 11 same-gender
      dizygotic healthy control twin pairs. RESULTS: Repeated-measures volume analysis
      of covariance revealed decreased whole brain volume in the patients with
      schizophrenia as compared with their co-twins and with healthy twin pairs.
      Decreased white matter volume was found in discordant twin pairs compared with
      healthy twin pairs, particularly in the monozygotic twin pairs. A decrease in
      gray matter was found in the patients compared with their co-twins and compared
      with the healthy twins. CONCLUSIONS: The results suggest that the decreases in
      white matter volume reflect the increased genetic risk to develop schizophrenia,
      whereas the decreases in gray matter volume are related to environmental risk
      factors. Study of genes involved in the (maintenance) of white matter structures
      may be particularly fruitful in schizophrenia.

PMID- 14732593
TI  - Gyrification in first-episode schizophrenia: a morphometric study.
AB  - BACKGROUND: A number of studies have found localized differences in the
      appearance and extent of cortical folding between the brains of schizophrenic
      patients and healthy control subjects. This study aimed to determine whether
      there are differences in gyral folding in schizophrenia by conducting a detailed
      analysis of magnetic resonance images. METHODS: Thirty-four young adults in their
      first episode of schizophrenia and 36 age-matched, healthy control subjects were
      studied. The gyrification index (GI), the ratio of the inner and outer cortical
      surface contours, was measured bilaterally on every second 1.88-mm image slice in
      four specifically defined lobar regions. Independent t tests were conducted for
      each region, followed by post hoc analysis of variance testing for the effects of
      laterality. RESULTS: Gyrification index values between groups corresponded
      closely in the occipital and parietal regions but were significantly increased in
      the right temporal lobe of the schizophrenic patients. Calculating the GI by two
      different methods (used in previous studies) notably affected results.
      Gyrification index values were significantly lateralized in the frontal and
      temporal regions, with no group x side interactions. CONCLUSIONS: Differences in
      the temporal lobe GI of first-episode schizophrenic patients might reflect
      disturbed or abnormal connectivity. Further examination of specific sources of
      sulco-gyral difference in schizophrenia is required to clarify this.

PMID- 14732594
TI  - Normal cerebral volume asymmetries in early onset schizophrenia.
AB  - BACKGROUND: Abnormalities in cerebral lateralization are thought to reflect early
      neurodevelopmental defects in schizophrenia. The aim of this study was to examine
      whether there is abnormal brain lateralization in early onset schizophrenia (EOS)
      and whether it is related to the unusually early onset of the disorder. METHODS:
      Adolescent patients with recent onset schizophrenia and an equal number of
      matched control subjects participated in the study. The volumes of the
      occipitoparietal, sensorimotor, premotor, prefrontal, and temporal regions were
      measured bilaterally from magnetic resonance images using stereological methods.
      Asymmetry indexes were calculated for each region using the formula ([R - L]/[R +
      L]) x 100. A composite index of asymmetry (torque) was computed as the sum of the
      five index scores. RESULTS: A total of 40 patients with EOS and 40 age-matched
      controls were enrolled. There were no group differences in demographic
      characteristics. No group differences in brain asymmetry measures were seen in
      any of the brain regions examined. CONCLUSIONS: The unusually early onset of
      schizophrenia in this population does not appear to be associated with
      abnormalities in hemispheric lateralization.

PMID- 14732592
TI  - Prefrontal cortical thickness in first-episode psychosis: a magnetic resonance
      imaging study.
AB  - BACKGROUND: Findings from postmortem studies suggest reduced prefrontal cortical
      thickness in schizophrenia; however, cortical thickness in first-episode
      schizophrenia has not been evaluated using magnetic resonance imaging (MRI).
      METHODS: Prefrontal cortical thickness was measured using MRI in first-episode
      schizophrenia patients (n = 17), first-episode affective psychosis patients (n =
      17), and normal control subjects (n = 17); subjects were age-matched within 2
      years and within a narrow age range (18-29 years). A previous study using the
      same subjects reported reduced prefrontal gray matter volume in first-episode
      schizophrenia. Manual editing was performed on those prefrontal segmentations
      before cortical thickness was measured. RESULTS: Prefrontal cortical thickness
      was not significantly different among groups. Prefrontal gray matter volume and
      thickness were, however, positively correlated in both schizophrenia and control
      subjects. The product of boundary complexity and thickness, an alternative
      measure of volume, was positively correlated with volume for all three groups.
      Finally, age and age at first medication were negatively correlated with
      prefrontal cortical thickness only in first-episode schizophrenia. CONCLUSIONS:
      This study demonstrates the potential usefulness of MRI for the study of cortical
      thickness abnormalities in schizophrenia. Correlations between cortical thickness
      and age and between cortical thickness and age at first medication suggest that
      the longer the schizophrenic process has been operative, the thinner the
      prefrontal cortex, although this needs confirmation in a longitudinal study.

PMID- 14732595
TI  - Near-infrared spectroscopy analysis of frontal lobe dysfunction in schizophrenia.
AB  - BACKGROUND: Previous studies have shown that near-infrared spectroscopy (NIRS)
      has high temporal resolution, requires little restraint, and is suitable for
      examining the effect of psychological tasks on brain circulation. In the present
      study, frontal function in schizophrenic patients was analyzed by NIRS during
      random number generation (RNG), ruler-catching (RC), and sequential finger-to
      thumb (SFT) tasks. METHODS: Two sets of NIRS probes were attached to the
      foreheads of 13 schizophrenic patients and 10 control subjects approximately at
      Fp1-F7 and Fp2-F8. Near-infrared spectroscopy was conducted at a sampling rate of
      1 Hz, with the pathlength being determined by time-resolved spectroscopy with
      differential pathlength factor measurements. The absolute changes in oxygenated
      (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin concentrations in response to
      each task were measured, and total hemoglobin (total-Hb) concentration was
      calculated as the sum of the two. RESULTS: During RNG task, total- and oxy-Hb
      concentrations increased, and deoxy-Hb decreased, but the responses were
      significantly smaller in schizophrenic patients. During RC task, oxy-Hb in
      schizophrenic patients tended to decrease, in contrast to the mostly increasing
      response in control subjects. No group difference was observed during SFT task.
      CONCLUSIONS: Task-dependent profile of functional abnormalities was observed in
      schizophrenic frontal brain metabolism. These results support the usefulness of
      NIRS data in investigating frontal lobe dysfunction and evaluating
      psychopathologic condition in schizophrenic patients.

PMID- 14732596
TI  - High-dose glycine added to olanzapine and risperidone for the treatment of
      schizophrenia.
AB  - BACKGROUND: Clinical trials indicate that glycine site agonists of the N-methyl-D
      aspartate (NMDA) receptors may reduce negative and cognitive symptoms in
      treatment-resistant schizophrenia when used as adjuvants to conventional
      antipsychotics but possibly not to clozapine. In this study, we assessed whether
      high-dose glycine may also be therapeutically beneficial when added to olanzapine
      and risperidone treatment. METHODS: Seventeen olanzapine- or risperidone-treated
      schizophrenia patients participated in a double-blind, placebo-controlled, 6-week
      crossover treatment trial with.8 g/kg/day glycine added to their ongoing
      antipsychotic medication. Clinical assessments were performed biweekly throughout
      the study. Clinical laboratory parameters and amino acid serum levels were
      monitored. RESULTS: Glycine treatment was well tolerated and resulted in a
      significant (p <.0001) 23% +/- 8% reduction in negative symptoms. Significant
      improvements were also registered in cognitive and positive symptoms. The
      negative symptoms improvement remained significant even following covariation for
      changes in other symptom clusters and extrapyramidal side effects. High
      posttreatment glycine serum levels significantly predicted (r =.60) clinical
      response. CONCLUSIONS: These findings indicate that the efficacy of olanzapine
      and risperidone may be augmented using high-dose adjuvant glycine treatment and
      suggest that these atypical antipsychotics may affect NMDA receptor-mediated
      neurotransmission differently than clozapine.

PMID- 14732597
TI  - Prefrontal lesion reverses abnormal mesoaccumbens response in an animal model of
      schizophrenia.
AB  - BACKGROUND: A neonatal hippocampal lesion induces postpubertal behavioral
      alterations resembling phenomena observed in schizophrenia. We have recently
      reported that nucleus accumbens neurons exhibit altered response to ventral
      tegmental area activation, but only when animals with this lesion reach
      adulthood. Because a prefrontal cortical lesion eliminates postpubertal abnormal
      behaviors in these animals, we investigated whether altered accumbens responses
      were reversed with this manipulation. METHODS: In vivo intracellular recordings
      were conducted in accumbens neurons in rats that had received neonatal
      hippocampal lesions combined with either adult prefrontal cortical lesion or sham
      treatment. Accumbens response to mesolimbic pathway activation was recorded in
      these animals. RESULTS: Accumbens neurons from animals with a neonatal
      hippocampal lesion and an adult prefrontal sham operation still showed altered
      accumbens response to mesolimbic stimulation. On the other hand, most animals
      with combined neonatal hippocampal and adult prefrontal lesions exhibited
      responses similar to those of naive animals. CONCLUSIONS: This result suggests
      that abnormal behaviors in these animals might be related to excessive prefrontal
      drive of accumbens neurons upon dopamine activation.

PMID- 14732599
TI  - Hippocampal structural asymmetry in unsuccessful psychopaths.
AB  - BACKGROUND: Structural and functional hippocampal abnormalities have been
      previously reported in institutionalized psychopathic and aggressive populations.
      This study assessed whether prior findings of a right greater than left (R > L)
      functional asymmetry in caught violent offenders generalize to the structural
      domain in unsuccessful, caught psychopaths. METHODS: Left and right hippocampal
      volumes were assessed using structural magnetic resonance imaging (MRI) in 23
      control subjects, 16 unsuccessful psychopaths, and 12 successful (uncaught)
      community psychopaths and transformed into standardized space. RESULTS:
      Unsuccessful psychopaths showed an exaggerated structural hippocampal asymmetry
      (R > L) relative both to successful psychopaths and control subjects (p <.007)
      that was localized to the anterior region. This effect could not be explained by
      environmental and diagnostic confounds and constitutes the first brain imaging
      analysis of successful and unsuccessful psychopaths. CONCLUSIONS: Atypical
      anterior hippocampal asymmetries in unsuccessful psychopaths may reflect an
      underlying neurodevelopmental abnormality that disrupts hippocampal-prefrontal
      circuitry, resulting in affect dysregulation, poor contextual fear conditioning,
      and insensitivity to cues predicting capture.

PMID- 14732600
TI  - Support for RGS4 as a susceptibility gene for schizophrenia.
AB  - BACKGROUND: The gene encoding the regulator of G-protein signaling 4 has recently
      been associated with susceptibility to schizophrenia. This finding is
      particularly interesting, because it was replicated within the same study and
      also because there are functional, positional, and expression data to support the
      regulator of G-protein signaling 4 as a schizophrenia candidate gene. Although
      the original report was highly suggestive, a limitation was that the study was
      conducted on rather small samples. METHODS: We have examined a large case (n =
      709) control (n = 710) sample for association between schizophrenia using four
      markers investigated in the earlier study, denoted single nucleotide
      polymorphisms 1, 4, 7, and 18. RESULTS: We were able to replicate the
      associations with single nucleotide polymorphisms 4 and 18 that had previously
      been reported individually and have also identified significant association with
      haplotypes constructed from single nucleotide polymorphisms 1 and 4. CONCLUSIONS:
      Our data give modest support for the hypothesis that the regulator of G-protein
      signaling 4 is a susceptibility gene for schizophrenia.

PMID- 14732598
TI  - Shape of caudate nucleus and its cognitive correlates in neuroleptic-naive
      schizotypal personality disorder.
AB  - BACKGROUND: We measured the shape of the head of the caudate nucleus with a new
      approach based on magnetic resonance imaging (MRI) in schizotypal personality
      disorder (SPD) subjects in whom we previously reported decreased caudate nucleus
      volume. We believe MRI shape analysis complements traditional MRI volume
      measurements. METHODS: Magnetic resonance imaging scans were used to measure the
      shape of the caudate nucleus in 15 right-handed male subjects with SPD, who had
      no prior neuroleptic exposure, and in 14 matched normal comparison subjects. With
      MRI processing tools, we measured the head of the caudate nucleus using a shape
      index, which measured how much a given shape deviates from a sphere. RESULTS: In
      relation to comparison subjects, neuroleptic never-medicated SPD subjects had
      significantly higher (more "edgy") head of the caudate shape index scores,
      lateralized to the right side. Additionally, for SPD subjects, higher right and
      left head of the caudate SI scores correlated significantly with poorer
      neuropsychological performance on tasks of visuospatial memory and
      auditory/verbal working memory, respectively. CONCLUSIONS: These data confirm the
      value of measuring shape, as well as volume, of brain regions of interest and
      support the association of intrinsic pathology in the caudate nucleus, unrelated
      to neuroleptic medication, with cognitive abnormalities in the schizophrenia
      spectrum.

PMID- 14732601
TI  - A nonsense mutation in the synaptogyrin 1 gene in a family with schizophrenia.
AB  - BACKGROUND: Chromosome 22q is one of the important regions repeatedly being
      implicated in schizophrenia. In this region, our group previously reported an
      association of a CAG repeat marker (22CH3) with schizophrenia in the Indian
      population. Because Synaptogyrin 1 (SYNGR1), associated with presynaptic vesicles
      in neuronal cells, lies within 1 million base pairs of this marker, it is a
      potential candidate gene for schizophrenia. METHODS: We sequenced all six exons
      and flanking splice junctions of the SYNGR1 gene. We also carried out reverse
      transcriptase polymerase chain reaction and Northern blot analysis for exon 2
      containing transcript of the SYNGR1 gene. RESULTS: We found a novel nonsense
      mutation (Trp27Ter) in exon 2 of the SYNGR1 gene in a family multiply affected
      with schizophrenia. Reverse transcriptase polymerase chain reaction and Northern
      blot analyses revealed that exon 2 containing transcript of this gene is
      expressed in the brain. CONCLUSIONS: Because the SYNGR1 gene is involved in
      presynaptic pathways, reduced levels of this protein might play some role in the
      pathogenesis of schizophrenia.

PMID- 14732602
TI  - Good and bad death: introduction.

PMID- 14732603
TI  - The good, the bad, and the unresolved death in Kaliai.
AB  - Lusi-Kaliai speakers in West New Britain, Papua New Guinea consider death to be
      either good or bad depending on whether it is the consequence of bad social
      relationships and causes social upheaval. A good death is under the control of
      the dying person and is the result of the natural process of aging. Good deaths
      are the ideal, but are rare in Kaliai. Bad death is more common and implies a
      rupture of social relations and results in the destruction of peace and social
      order. A death may be unresolved because people disagree as to its cause and its
      meaning for others. Strife resulting from an unresolved death may be irreparable,
      making closure impossible. The resulting social dysfunction can lead to further
      death and the breakdown of the community. However, when people understand the
      cause of death and can identify the causative agent, it is possible to resolve
      the problems leading to the death and restore order. Case studies illustrate how
      particular deaths fit these categories and how the people of Kaliai struggle to
      explain death, to cope with its inevitability, and to repair the social
      disruption in its wake.

PMID- 14732604
TI  - Dying peacefully: considering good death and bad death in Kwahu-Tafo, Ghana.
AB  - People in Kwahu-Tafo, a rural town in Southern Ghana, regard a peaceful death as
      a 'good death'. 'Peaceful' refers to the dying person having finished all
      business and made peace with others before his/her death and implies being at
      peace with his/her own death. It further refers to the manner of dying: not by
      violence, an accident or a fearsome disease, not by foul means and without much
      pain. A good and peaceful death comes 'naturally' after a long and well-spent
      life. Such a death preferably takes place at home, which is the epitome of
      peacefulness, surrounded by children and grandchildren. Finally, a good death is
      a death which is accepted by the relatives. This 'definition' of good death--'bad
      death' is its opposite--does not imply, however, that it is a fixed category. The
      quality of one's death is liable to social and political manoeuvre and,
      therefore, inherently ambiguous. The good death of a very old and successful
      person can be decried by the younger generation as the death of a witch who
      managed to live long at the expense of young people who died prematurely. The
      article is based on anthropological fieldwork carried out intermittently from
      1971 to the present day.

PMID- 14732605
TI  - Cultural scripts for a good death in Japan and the United States: similarities
      and differences.
AB  - Japan and the United States are both post-industrial societies, characterised by
      distinct trajectories of dying. Both contain multiple "cultural scripts" of the
      good death. Seale (Constructing Death: the Sociology of Dying and Bereavement,
      Cambridge University Press, Cambridge, 1998) has identified at least four
      "cultural scripts", or ways to die well, that are found in contemporary
      anglophone countries: modern medicine, revivalism, an anti-revivalist script and
      a religious script. Although these scripts can also be found in Japan, different
      historical experiences and religious traditions provide a context in which their
      content and interpretation sometimes differ from those of the anglophone
      countries. To understand ordinary people's ideas about dying well and dying
      poorly, we must recognise not only that post-industrial society offers multiple
      scripts and varying interpretive frameworks, but also that people actively select
      from among them in making decisions and explaining their views. Moreover, ideas
      and metaphors may be based on multiple scripts simultaneously or may offer
      different interpretations for different social contexts. Based on ethnographic
      fieldwork in both countries, this paper explores the metaphors that ordinary
      patients and caregivers draw upon as they use, modify, combine or ignore these
      cultural scripts of dying. Ideas about choice, time, place and personhood,
      elements of a good death that were derived inductively from interviews, are
      described. These Japanese and American data suggest somewhat different concerns
      and assumptions about human life and the relation of the person to the wider
      social world, but indicate similar concerns about the process of medicalised
      dying and the creation of meaning for those involved. While cultural differences
      do exist, they cannot be explained by reference to 'an American' and 'a Japanese'
      way to die. Rather, the process of creating and maintaining cultural scripts
      requires the active participation of ordinary people as they in turn respond to
      the constraints of post-industrial technology, institutions, demographics and
      notions of self.

PMID- 14732606
TI  - Good enough death: autonomy and choice in Australian palliative care.
AB  - This paper draws upon Australian fieldwork to trace the changing notions of a
      good death held by hospice and palliative care practitioners. Palliative care
      practitioners search for an ideology to inform their practice within the context
      of a complex society for which there is no one good death. Social demographics,
      the multicultural nature of society and institutional constraints frame the
      experience of dying in complex ways, while contemporary social responses to dying
      reflect the uncertainties held by many Australians. Despite the fragmentation
      evident within contemporary Australian society, the hospice movement in Australia
      and in other Western contexts has sought to reintroduce a ritual for dying. The
      good death ideology of the original hospice movement proposed a manner of dying
      in which open communication and acceptance of death were actively encouraged. The
      hospice model of a good death, however, has become increasingly inappropriate in
      the current climate of patient autonomy and consumer choice. The practice of
      palliative care, a holistic form of care for dying people, which follows the
      individualistic ethic of choice, has emerged from and replaced the original
      hospice movement. Consequently, the good death of the original hospice movement
      has been abandoned in favour of a philosophy of a 'good enough' death. However,
      what may appear a compromise informed by ethical practice masks a return to
      routine medical practices and a hierarchy of care which prioritises the physical
      management of symptoms. It appears that while palliative care practitioners may
      often fail in their facilitation of a good death for their patients, they can be
      proactive in alleviating their patients' pain and physical discomfort.

PMID- 14732607
TI  - Narrative nuances on good and bad deaths: internists' tales from high-technology
      work places.
AB  - Public and professional discourses in American society about what constitutes a
      "good death" have flourished in recent decades, as illustrated by the pivotal
      SUPPORT study and the growing palliative care movement. This paper examines a
      distinctive medical discourse from high-technology academic medical centers
      through an analysis of how physicians who are specialists in internal medicine
      tell stories about the deaths of patients in their care. 163 physicians from two
      major academic medical centers in the United States completed both qualitative
      open interviews and quantitative attitudinal measures on a recent death and on
      the most emotionally powerful death they experienced in the course of their
      careers. A subsample of 75 physicians is the primary source for the qualitative
      analysis, utilizing Atlas-ti."Good death" and "bad death" are common in popular
      discourse on death and dying. However, these terms are rarely used by physicians
      in this study when discussing specific patients and individual deaths. Rather,
      physicians' narratives are nuanced with professional judgments about what
      constitutes quality end-of-life care. Three major themes emerge from these
      narratives and frame the positive and negative characteristics of patient death.
      Time and Process: whether death was expected or unexpected, peaceful, chaotic or
      prolonged; Medical Care and Treatment Decisions: whether end-of-life care was
      rational and appropriate, facilitating a "peaceful" or "gentle" death, or futile
      and overly aggressive, fraught with irrational decisions or adverse events;
      Communication and Negotiation: whether communication with patients, family and
      medical teams was effective, leading to satisfying management of end-of-life
      care, or characterized by misunderstandings and conflict. When these physicians'
      narratives about patient deaths are compared with the classic sociological
      observations made by Glaser and Strauss in their study A Time for Dying (1968),
      historical continuities are evident as are striking differences associated with
      rapid innovation in medical technologies and a new language of medical futility.
      This project is part of a broader effort in American medicine to understand and
      improve end-of-life care.

PMID- 14732608
TI  - "You're not going to dehydrate mom, are you?": Euthanasia, versterving, and good
      death in the Netherlands.
AB  - In 1996, a debate erupted in the Netherlands about versterven: dying as a result
      of abstaining from eating and drinking. This discussion initially appeared to be
      one of the many side-shows to the wider Dutch euthanasia debate, but it continued
      to dominate the debate for the next few years, with newspaper headlines reporting
      "involuntary dehydration" in nursing homes. Part of the reason for this was the
      term itself. Introduced to refer to terminal dehydration, the word versterven had
      peculiar connotations and this, together with the way in which it was used,
      caused much confusion and controversy. Was versterven related to euthanasia? Did
      it denote dying naturally and peacefully or a horrible death imposed on helpless
      psychogeriatric patients? Was it (could it be) voluntary? Was the patient in
      control? Was it good death? This paper examines the discussion about, and the
      media representations of, versterven, focusing on its ambiguity and its
      relationship to good death.

PMID- 14732609
TI  - Media constructions of dying alone: a form of 'bad death'.
AB  - In this study, newspaper accounts of people who die alone are analysed, drawing
      on a sample of 90 articles in the anglophone press that appeared in October 1999.
      Dying alone is represented as a fearful fate and a moral affair, often being the
      outcome of an undesirable personal character, either of the deceased or of
      onlookers, or involving the failings of society at large. It is frequently
      portrayed as occurring to people who are either geographically or socially
      distant from 'home', so that an imagined community of readers is encouraged to
      contemplate a death alone as the consequence of personal or societal breakdown. A
      degree of stigmatisation, sometimes of those who die alone, sometimes of those
      perceived to have caused this event, was evident. The negative evaluation of
      death alone parallels that found in some traditional societies where a death far
      from home is considered 'bad'. Dying alone contrasts significantly with the
      sociable, 'good', confessional deaths of newspaper columnists and other media
      celebrities facing terminal illness.

PMID- 14732610
TI  - Ancient euthanasia: 'good death' and the doctor in the graeco-Roman world.
AB  - This article maps the concept of 'good death' (euthanasia) in the ancient world
      and explores the marginal role of the doctor at a 'good dying'. His assistance
      was not needed when the Homeric warrior died as a hero and was expected to accept
      death with resignation. Later the city-state regarded as heroes the men fallen
      for the cause of the community, honouring these model citizens as those who died
      well. In the more individualistic age of Hellenism and the Roman Empire, a death
      in luxury or without suffering could be styled euthanasia. The doctor had neither
      a place in those acts of dying nor in cases of natural death. He shunned death as
      a failure of his art. Sometimes a doctor was called in to assist in voluntary
      death, a role that was not forbidden by the Hippocratic oath. An appeal to this
      oath by opponents of euthanasia in the modern sense of the word therefore is
      mistaken.

PMID- 14732611
TI  - Good death and bad death in ancient Israel according to biblical lore.
AB  - In the view of the ancient Israelites, as expressed in the Hebrew Bible, death is
      good or at least acceptable (1) after a long life, (2) when a person dies in
      peace, (3) when there is continuity in the relation with the ancestors and the
      heirs, and (4) when one will be buried in one's own land. Death is experienced as
      bad when (1) it is premature, (2) violent, especially when it is shameful (e.g.,
      when a man is killed by a woman), (3) when a person does not have an heir, and
      (4) when one does not receive a proper burial. It is remarkable that in the
      literature of ancient Israel common elements like the cult of the dead and the
      belief in retribution after death, are not explicitly mentioned and therefore do
      not function as a comfort for death. Also, from a theological point of view
      emphasis is placed on this life. A positive attitude towards martyrdom is
      missing. This results in a way of coping with death which has many 'modern'
      elements or which may help modern people to face death.

PMID- 14732613
TI  - Reporting of randomized clinical trials and other population-based research: a
      priority of Archives of Neurology.

PMID- 14732614
TI  - When is ataxia not ataxia?

PMID- 14732615
TI  - Multiminicore myopathy, central core disease, malignant hyperthermia
      susceptibility, and RYR1 mutations: one disease with many faces?

PMID- 14732616
TI  - Paraneoplastic neurologic disorders: windows into neuronal function and tumor
      immunity.

PMID- 14732618
TI  - Safety of latest-generation self-expanding stents in patients with NASCET
      ineligible severe symptomatic extracranial internal carotid artery stenosis.
AB  - BACKGROUND: Patients with symptomatic extracranial internal carotid artery
      stenosis (> or =70%) benefit from carotid endarterectomy when compared with
      medical management. However, independent risk factors can significantly increase
      the combined stroke and death risk after carotid endarterectomy. Carotid
      angioplasty and stenting (CAS) is a therapeutic option in patients who are
      otherwise at high risk or ineligible for carotid endarterectomy. Previous
      generation self-expanding stents were hampered by length foreshortening, which
      limited their application in multifactorial occlusive extracranial internal
      carotid artery stenosis. METHODS: This is a single-center, prospective, open
      label, safety study of CAS with the latest-generation self-expanding stents in
      patients with extracranial internal carotid artery symptomatic stenosis (> or
      =70%). All patients included were adjudicated to be ineligible for carotid
      endarterectomy by a vascular surgeon and/or a neurologist according to the
      exclusion criteria. Primary adverse events included death and all strokes
      (ipsilateral and contralateral). Secondary adverse events included transient
      ischemic attack, myocardial infarction, stent thrombosis, need for
      reintervention, and presence of hematomas. All adverse events were recorded at 24
      hours, 30 days, and 6 months after CAS. RESULTS: Between June 1, 2001, and
      January 30, 2003, 23 consecutive patients (14 women and 9 men; mean age, 65
      years; age range, 48-85 years) underwent 24 extracranial CAS procedures with the
      latest-generation self-expanding stents. All patients had one or multiple
      criteria for ineligibility according to the North American Symptomatic Carotid
      Endarterectomy Trial. Extracranial CAS was successful in all patients, with
      average residual stenosis of less than 20%. One patient (4%) experienced a stroke
      by the 30-day periprocedure examination. The total number of primary adverse
      events at 6 months after CAS was 2 strokes (9%), 1 of which was contralateral to
      the stent placement; there were no deaths. Twenty-two patients were asymptomatic
      at 6 months, with a modified Rankin scale score of 1 or less. Of the 2 patients
      who had a stroke, 1 had a follow-up modified Rankin scale score of 3. CONCLUSION:
      Extracranial CAS with the latest-generation self-expanding stents is a valid
      alternative treatment in high-risk or North American Symptomatic Carotid
      Endarterectomy Trial-ineligible patients.

PMID- 14732617
TI  - The parkinsonian phenotype of spinocerebellar ataxia type 2.
AB  - BACKGROUND: We recently reported that spinocerebellar ataxia type 2 (SCA2) caused
      familial parkinsonism in 2 brothers with predominant symptoms of resting tremor,
      rigidity, and bradykinesia that responded to levodopa. OBJECTIVE: To investigate
      SCA2 as the possible cause of familial parkinsonism in our series and
      subsequently to analyze the correlation between the clinical manifestation and
      CAG repeat size in the ataxin-2 gene product. PATIENTS: One hundred thirty
      patients from 41 families with familial parkinsonism were examined for SCA2.
      Another 8 patients with the classic ataxic phenotype of SCA2 from 6 families were
      the control group. DESIGN: The length of expanded CAG repeat was analyzed by
      means of polymerase chain reaction. The clinical data and genetic findings in the
      parkinsonian phenotype were then compared with those in the ataxic phenotype.
      RESULTS: We found expanded CAG repeats in the ataxin-2 gene product in 7 patients
      from 4 families with parkin-sonism, which was about 10% of our familial
      parkinsonism series. The parkinsonian phenotype was characterized by resting
      tremor, rigidity, and bradykinesia. Only mild dysarthria, ataxic gait, and
      instability were noted, particularly in the late stage. Patients with the
      parkinsonian phenotype had an older mean +/- SD age of symptom onset (45.8 +/-
      13.9 years) and shorter mean +/- SD abnormal CAG length (36.2 +/- 1.1 repeats)
      than did those with the ataxic phenotype (26.9 +/- 11.0 years and 43.1 +/- 3.2
      repeats). Parkinsonian SCA2 responded well to levodopa. CONCLUSIONS: We conclude
      that SCA2 is a minor cause of familial parkinsonism, particularly in Taiwan. The
      parkinsonian phenotype is associated predominantly with a shorter abnormal range
      of CAG repeat lengths and older onset age. Because of the clinical resemblance
      among familial parkinsonisms, we suggest that SCA2 should be excluded in cases of
      familial parkinsonism.

PMID- 14732619
TI  - Idiopathic autonomic neuropathy: comparison of cases seropositive and
      seronegative for ganglionic acetylcholine receptor antibody.
AB  - BACKGROUND: The clinical characteristics of autoimmune autonomic neuropathy are
      only partially defined. More than 50% of patients with high levels of ganglionic
      acetylcholine receptor (AChR) autoantibodies have a combination of sicca complex
      (marked dry eyes and dry mouth), abnormal pupillary light response, upper
      gastrointestinal tract symptoms, and neurogenic bladder. OBJECTIVE: To compare
      patients with idiopathic autonomic neuropathy who were seropositive (n = 19) and
      seronegative (n = 87) for ganglionic AChR antibodies. DESIGN: Retrospective
      review of autonomic programmatic database. SETTING: Autonomic Disorders Program
      Project at Mayo Clinic College of Medicine, Rochester, Minn. PATIENTS: We
      evaluated a cohort of 87 patients with idiopathic autonomic neuropathy who had
      undergone full autonomic testing and neurological evaluation and who had a
      complete panel of paraneoplastic and ganglionic AChR antibodies. We compared
      patients seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR
      antibodies. RESULTS: The seropositive group had a significant overrepresentation
      of abnormal pupillary responses (12/18 [67%] vs 12/87 [14%]; P<.001), sicca
      complex (9/15 [60%] vs 11/47 [23%]; P =.01), and lower gastrointestinal tract
      dysautonomia (16/19 [84%] vs 48/85 [56%]; P =.02). A subacute mode of onset was
      more common in the seropositive group (12/19 [63%] vs 23/84 [27%]; P =.004).
      Results of quantitative autonomic function tests differed significantly in the 2
      groups only in the cardiovagal domain. Because subacute onset was overrepresented
      in the seropositive group, we analyzed the data separately, controlling for
      temporal profile (ie, the relationship between antibody status and symptoms while
      controlling for rate of onset). The relationships between antibody status and
      clinical profile (eg, presence of sicca complex, pupillary abnormalities, and
      lower gastrointestinal tract symptoms) generally remained significant regardless
      of onset rate, indicating that the associations are not due to temporal profile.
      CONCLUSIONS: These observations support the concept that ganglionic AChR
      antibodies are diagnostically and pathophysiologically important. Patients with
      orthostatic hypotension and prominent cholinergic dysautonomia are most likely to
      be seropositive for ganglionic AChR antibody.

PMID- 14732620
TI  - Three novel mutations of the spastin gene in Chinese patients with hereditary
      spastic paraplegia.
AB  - BACKGROUND: Hereditary spastic paraplegia is a group of genetically heterogeneous
      neurodegenerative disorders characterized by progressive spasticity of the lower
      limbs. The most common form of hereditary spastic paraplegia is caused by
      mutations in the spastin gene (SPG4), which encodes spastin, an adenosine
      triphosphatase associated with various cellular activities protein. OBJECTIVE: To
      investigate the Chinese patients with hereditary spastic paraplegia for mutations
      in SPG4. METHODS: DNA samples from 31 unrelated patients were analyzed for
      mutations in SPG4 by single-strand conformation polymorphism analysis and direct
      sequencing. All DNA samples were screened for mutations by the polymerase chain
      reaction, followed by electrophoresis and silver staining. Each new variant
      identified was analyzed in 50 control subjects to determine whether it is a
      polymorphism or a mutation. RESULTS: Three novel mutations were detected in 4
      affected individuals, including 2 missense mutations (T1258A and A1293G) and 1
      deletion mutation (1668-1670delCTA). CONCLUSIONS: To our knowledge, this is the
      first report of SPG4 mutations in the People's Republic of China. The percentage
      of involved Chinese families with autosomal dominant hereditary spastic
      paraplegia with an SPG4 mutation is 18% (4/22), lower than the estimated 40%
      linked to this locus.

PMID- 14732622
TI  - Plasma total homocysteine levels and cranial magnetic resonance imaging findings
      in elderly persons: the Cardiovascular Health Study.
AB  - BACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with
      an increased risk of vascular disease. Some studies have shown associations
      between tHcy level and small-vessel disease of the brain on magnetic resonance
      imaging (MRI). DESIGN: In the Cardiovascular Health Study, 622 elderly
      participants without a history of transient ischemic attack or stroke had results
      for tHcy level and cranial MRI. We sought associations between tHcy level and MRI
      findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We
      controlled for other factors, including levels of creatinine, folate, and
      vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype.
      RESULTS: After controlling for age and sex, tHcy level was not associated with
      the individual MRI findings. Further adjustments for other factors and other
      blood tests had little effect on these findings. The only significant finding was
      a linear trend across quintiles of tHcy level and a pattern of MRI findings
      combining infarcts and high white matter grade. The linear trend remained
      significant after controlling for other risk factors and atherosclerotic markers
      (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96
      11.20; P =.04 for linear trend) but was slightly diminished after further
      controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2;
      95% confidence interval, 0.81-13.10; P =.07 for linear trend). CONCLUSION: We
      were unable to confirm the results of previous studies with respect to tHcy level
      and individual MRI findings, although an association was seen for an MRI pattern
      combining infarcts and high white matter grade.

PMID- 14732621
TI  - Mild cognitive impairment can be distinguished from Alzheimer disease and normal
      aging for clinical trials.
AB  - BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state
      between the cognitive changes of normal aging and very early dementia and is
      becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The
      Memory Impairment Study (MIS) is a multicenter clinical trial in patients with
      MCI designed to evaluate whether vitamin E or donepezil is effective at delaying
      the time to a clinical diagnosis of AD. OBJECTIVE: To describe the baseline
      characteristics of patients with MCI recruited for the MIS and compare them with
      those of elderly controls and patients with AD in another clinical trial. DESIGN:
      Descriptive and comparative study of patients with MCI participating in a
      multicenter clinical trial. SETTING: Memory disorder centers in the United States
      and Canada. PATIENTS: A total of 769 patients with MCI, 107 cognitively normal
      elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR]
      0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS
      met operational criteria for amnestic MCI. Controls were recruited in parallel
      with the MCI group, underwent the same assessments, and had a CDR of 0. MAIN
      OUTCOME MEASURES: Clinical, neuropsychologic, functional, neuroimaging, and
      genetic measures. RESULTS: Mean +/- SD Alzheimer's Disease Assessment Scale
      Cognitive Subscale scores were 5.6 +/- 3.3 for controls, 11.3 +/- 4.4 for
      patients with MCI, 18.0 +/- 6.2 for the AD CDR 0.5 group, and 25.2 +/- 8.8 for
      the AD CDR 1.0 group. Compared with controls, patients with MCI were most
      impaired on memory tasks, with less severe impairments in other cognitive
      domains. Patients with MCI were more likely than controls but less likely than
      patients with AD to carry the apolipoprotein E epsilon4 allele. Patients with MCI
      had hippocampal volumes that were intermediate between those of controls and
      patients with AD. CONCLUSIONS: Patients with MCI had a predominant memory
      impairment with relative sparing of other cognitive domains and were intermediate
      between clinically normal individuals and patients with AD on cognitive and
      functional ratings. These results demonstrate the successful implementation of
      operational criteria for this unique group of at-risk patients in a multicenter
      clinical trial.

PMID- 14732623
TI  - Cognitive reserve-mediated modulation of positron emission tomographic
      activations during memory tasks in Alzheimer disease.
AB  - BACKGROUND: Cognitive reserve (CR) is the ability of an individual to cope with
      advancing brain pathological abnormalities so that he or she remains free of
      symptoms. Epidemiological data and evidence from positron emission tomography
      suggest that it may be mediated through education or IQ. OBJECTIVE: To
      investigate CR-mediated differential brain activation in Alzheimer disease (AD)
      subjects compared with healthy elderly persons. PARTICIPANTS: Using radioactive
      water positron emission tomography, we scanned 12 AD patients and 17 healthy
      elderly persons while performing a serial recognition memory task for
      nonverbalizable shapes under 2 conditions: low demand, in which one shape was
      presented in each study trial, and titrated demand, in which the study list
      length was adjusted so that each subject recognized shapes at approximately 75%
      accuracy. Positron emission tomographic scan acquisition included the encoding
      and recognition phases. A CR factor score that summarized years of education,
      National Adult Reading Test estimated IQ, and Wechsler Adult Intelligence Scale
      Revised vocabulary subtest score (explaining 71% of the total variance) was used
      as an index of CR. Voxel-wise, multiple regression analyses were performed with
      the "activation" difference (titrated demand-low demand) as the dependent
      variables and the CR factor score as the independent one. Brain regions where
      regression slopes differed between the 2 groups were identified. RESULTS: The
      slopes were significantly more positive for the AD patients in the left
      precentral gyrus and in the left hippocampus and significantly more negative in
      the right fusiform, right middle occipital, left superior occipital, and left
      middle temporal gyri. CONCLUSION: Brain regions where systematic relationships
      (slopes) between subjects' education-IQ and brain activation differ as a function
      of disease status may mediate the differential ability to cope with (ie, delay or
      modify) clinical manifestations of AD.

PMID- 14732624
TI  - Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements:
      the Cache County Study.
AB  - BACKGROUND: Antioxidants may protect the aging brain against oxidative damage
      associated with pathological changes of Alzheimer disease (AD). OBJECTIVE: To
      examine the relationship between antioxidant supplement use and risk of AD.
      DESIGN: Cross-sectional and prospective study of dementia. Elderly (65 years or
      older) county residents were assessed in 1995 to 1997 for prevalent dementia and
      AD, and again in 1998 to 2000 for incident illness. Supplement use was
      ascertained at the first contact. SETTING: Cache County, Utah. PARTICIPANTS:
      Among 4740 respondents (93%) with data sufficient to determine cognitive status
      at the initial assessment, we identified 200 prevalent cases of AD. Among 3227
      survivors at risk, we identified 104 incident AD cases at follow-up. MAIN OUTCOME
      MEASURE: Diagnosis of AD by means of multistage assessment procedures. RESULTS:
      Analyses of prevalent and incident AD yielded similar results. Use of vitamin E
      and C (ascorbic acid) supplements in combination was associated with reduced AD
      prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and
      incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A
      trend toward lower AD risk was also evident in users of vitamin E and
      multivitamins containing vitamin C, but we saw no evidence of a protective effect
      with use of vitamin E or vitamin C supplements alone, with multivitamins alone,
      or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin
      C supplements in combination is associated with reduced prevalence and incidence
      of AD. Antioxidant supplements merit further study as agents for the primary
      prevention of AD.

PMID- 14732625
TI  - Effects of high-frequency stimulation on subthalamic neuronal activity in
      parkinsonian patients.
AB  - BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is a
      neurosurgical alternative to medical treatment in levodopa-responsive forms of
      Parkinson disease. The mechanism of action of STN stimulation remains
      controversial, although an inhibition of overactive STN neurons has been
      postulated. OBJECTIVE: To determine the effects of high-frequency STN stimulation
      on the neuronal activity of STN neurons in Parkinson disease patients. PATIENTS:
      Single-unit recordings of the neuronal activity of the STN were obtained before,
      during, and after the application of intra-STN electrical stimulation in 15
      Parkinson disease patients. Changes in firing frequency and pattern were analyzed
      using various combinations of stimulus frequency (range, 14-140 Hz). RESULTS:
      Stimulation at a frequency greater than 40 Hz applied within the STN
      significantly decreased the firing frequency and increased the burst-like
      activity in the firing pattern of STN neurons. An aftereffect was observed in
      cells that had been totally inhibited during high-frequency stimulation.
      CONCLUSION: The beneficial effects of high-frequency stimulation result from a
      change in the firing pattern of cellular discharge and a blockade of the
      spontaneous overactivity of STN neurons.

PMID- 14732626
TI  - Predictors of impaired daytime sleep and wakefulness in patients with Parkinson
      disease treated with older (ergot) vs newer (nonergot) dopamine agonists.
AB  - BACKGROUND: Patients with Parkinson disease (PD) treated with the nonergot
      dopamine agonists pramipexole dihydrochloride and ropinirole hydrochloride have
      been reported to have sleep attacks without warning. OBJECTIVE: To perform a
      systematic evaluation of excessive daytime sleepiness using standard
      polysomnographic techniques. DESIGN: Two overnight studies and daytime sleep
      tests were performed on a prospective sample. Pathologic daytime sleep latency
      was indexed by a mean Multiple Sleep Latency Test score of no greater than 5
      minutes or a mean Maintenance of Wakefulness Test latency of no greater than 20
      minutes. PATIENTS AND SETTING: Eighty nondemented, independent PD patients
      treated with dopamine agonists at the Toronto Western Hospital Sleep Research
      Unit, Toronto, Ontario. RESULTS: Patients treated with pramipexole
      dihydrochloride (n = 29), ropinirole (n = 28), or bromocriptine mesylate or
      pergolide mesylate (n = 23) did not differ with respect to mean Multiple Sleep
      Latency Test scores (overall, 12.1 minutes [SD, 5.1 minutes], F(2,77) = 0.11; P
      =.90) or mean Maintenance of Wakefulness Test latencies (overall, 26.7 minutes
      [SD, 5.4 minutes]; F(2,77) = 1.1; P =.29). Fifteen patients (18.8%) exhibited
      pathologic daytime sleep latencies. The main risk factor associated with
      pathologic daytime sleep latency was high levodopa dosage equivalents (>867.5 mg;
      odds ratio, 4.2; 95% confidence interval, 1.3-13.7). Subjective accounts of
      daytime sleep and wakefulness, as indexed by scores on the Epworth Sleepiness
      Scale, were not related to impaired daytime sleepiness or wakefulness (chi(2)(1)
      [n = 80], 0.13; P =.72). CONCLUSIONS: Total dopaminergic drug dose rather than
      the specific dopamine agonist used is the best predictor of daytime sleepiness in
      PD patients receiving dopamine agonist therapy. Physicians concerned with daytime
      hypersomnolence in PD patients treated with dopamine agonists and receiving high
      levodopa dosage equivalents should consider polysomnographic monitoring for
      impaired daytime sleep latency.

PMID- 14732627
TI  - Multiminicore disease in a family susceptible to malignant hyperthermia:
      histology, in vitro contracture tests, and genetic characterization.
AB  - BACKGROUND: Histological anomalies associated with malignant hyperthermia (MH)
      have been scarcely reported. In some patients susceptible to MH (MHS), central
      cores have been identified and a genetic association has been proposed, but
      multiminicore lesions have not been systematically reported. OBJECTIVE: To
      analyze the association between multiminicores and MHS in a large family with MH
      with an approach combining histology, in vitro contracture tests, and genetic
      analysis. PATIENTS AND METHODS: Twenty-nine members of an MH family (147 members)
      were investigated. MAIN OUTCOME MEASURES: Muscle biopsy specimens were analyzed
      histologically and with in vitro contracture tests. Genetic analyses were
      performed to determine the presence of mutations in the ryanodine receptor (RYR1)
      gene. RESULTS: According to the gold standard in vitro contracture tests, 17
      patients were diagnosed as having MHS and 10 as not being susceptible.
      Multiminicores were found in 16 of the 17 MHS patients and in a single
      nonsusceptible participant. A linkage between the MH trait and the RYR1 locus in
      chromosome 19 was demonstrated, whereas no already known mutations were found.
      Two missense heterozygous mutations (R2676W and T2787S) were identified from
      sequencing of the entire coding complementary DNA. Overall, we found a
      significant association between MHS and the presence of multiminicores (chi(2) =
      26.5, P<.001) on the one hand and the presence of new mutations in the RYR1 gene
      (chi(2) = 19.0, P<.001) on the other hand. This remarkably high occurrence of
      multiminicores in an MHS family is uncommon, and genetic analyses indicate that
      the association between multiminicores and MHS is linked to a novel R2656W and
      T2787S substitution present on the same allele of the RYR1 gene. CONCLUSIONS:
      These results indicate that multiminicore lesions are observed in MHS patients
      with neither clinical signs related to multiminicore disease nor histological
      features of congenital myopathies. These multiminicore lesions may be secondary
      to mutations in the RYR1 gene. As a consequence, these patients must be
      distinguished from patients with multiminicore disease and from other MHS
      patients for whom multiminicores are not observed.

PMID- 14732628
TI  - Clinical progression and genetic analysis in hereditary spastic paraplegia with
      thin corpus callosum in spastic gait gene 11 (SPG11).
AB  - BACKGROUND: Hereditary spastic paraplegia (HSP) with thin corpus callosum (CC) is
      a rare neurodegenerative disorder classified as a complicated form of spastic
      paraplegia. Some patients with HSP with thin CC have previously been described in
      Japanese families, and the genetic locus was linked to chromosome 15q13-15.
      OBJECTIVE: Our objective was to further clinically and genetically characterize
      HSP with thin CC. PATIENTS: We describe the clinical, structural, and functional
      follow-up and the genetic characterization of 2 sisters aged 26 and 31 years who
      had severe spastic paraplegia and cognitive impairment. RESULTS: Magnetic
      resonance imaging revealed a thin CC with progressing frontoparietal cortical
      atrophy paralleled by cognitive decline. Using transcranial magnetic stimulation,
      we delineated a lack of transcallosal inhibition. Images obtained
      with(18)fluorodeoxyglucose positron emission tomography showed reduced cortical
      and thalamic hypometabolism that decreased further within 4 years. Additionally,
      combined axonal loss and demyelinating sensorimotor polyneuropathy were present.
      Because other family members were not affected, autosomal recessive inheritance
      was considered likely. Genetic analysis of this autosomal recessive HSP was
      consistent with the linkage to 15q13-15 (markers D15S971, D15S118, D15S994, and
      D15S659). No mutation was found within the SLC12A6 gene. CONCLUSION: Progressive
      axonal degeneration occurs in the corticocortical projections, corticospinal
      tract, and peripheral nerves in HSP with thin CC linking to chromosome 15q13-15
      in a German pedigree.

PMID- 14732629
TI  - Fatal familial insomnia: the first account in a family of Chinese descent.
AB  - BACKGROUND: Fatal familial insomnia (FFI) is an autosomal dominant disease linked
      to a mutation in the prion protein gene. Fatal familial insomnia is characterized
      by sleep disturbance and loss of neurons, with gliosis in the thalamic nuclei.
      OBJECTIVE: To describe the clinical, neurophysiological, radiological, and
      neuropathological data in a Chinese family with FFI. SETTING: Tertiary referral
      university hospital setting. PATIENTS: Patient 1 was a 36-year-old man who
      presented with insomnia and myoclonus. In the subsequent 9 months, he developed
      ataxia and dementia, followed by death. Patient 2 was the aunt of patient 1, and
      presented at the age of 47 years with insomnia, myoclonus, and dementia; her
      condition declined during a 12-month period. Genetic analysis was performed,
      followed by neuropathological and biochemical analysis of the disease-associated
      form of the prion protein PrPSc on the postmortem brain specimen. RESULTS:
      Molecular analysis demonstrated an aspartic acid to asparagine mutation at codon
      178 and homozygosity for methionine at codon 129. Both patients showed severe
      neuronal loss and prominent gliosis in the thalamus and brainstem involvement,
      with evidence of astrogliosis in the inferior olivary nucleus. Patient 1 also had
      neuronal loss and astrogliosis in the region of the superior colliculus and in
      the periaqueductal region. PrPSc was detected on Western blot analysis, and had a
      wide distribution. The strongest signals were present in the amygdala,
      hypothalamus, caudate, parahippocampal gyrus, periaqueductal gray matter, and
      mediodorsal thalamus. CONCLUSIONS: To our knowledge, this is the first report of
      FFI in a family of Chinese descent. This supports the worldwide distribution of
      FFI, and despite differences in genetic background, the clinical and pathological
      findings are similar to those found in white patients with FFI.

PMID- 14732630
TI  - Transverse myelitis in systemic sclerosis.
AB  - BACKGROUND: Neurological involvement occurs rarely with systemic sclerosis (SSc).
      Only a few cases of transverse myelopathy have been reported in the setting of
      SSc. OBJECTIVE: To describe a patient with SSc who developed transverse myelitis
      that improved during a course of immunosuppression. RESULTS: A 30-year-old woman
      with SSc presented with subacute onset of bilateral lower extremity weakness and
      numbness. Results of magnetic resonance imaging and cerebrospinal fluid studies
      supported a diagnosis of transverse myelitis. The patient responded favorably to
      a course of corticosteroids and cyclophosphamide. No overlapping autoimmune
      disorders were evident. Clinical follow-up showed significant recovery, with
      resolution of radiological abnormalities. CONCLUSION: Transverse myelitis can
      occur as a rare manifestation of SSc and may respond favorably to
      immunosuppressive therapy.

PMID- 14732631
TI  - Late "spectacular shrinking deficit"?

PMID- 14732632
TI  - Acute Brown-Sequard syndrome.

PMID- 14732633
TI  - Polymyositis: an ongoing discussion about a disease entity.
AB  - Since its first description more than a century ago, there has been much debate
      about the diagnostic entity polymyositis. Because initial observations were of
      individuals with dermatomyositis, it appeared that polymyositis was not possible
      without skin lesions. Distinctive clinical and histologic features of
      polymyositis were not established until the late 20th century. The identification
      of inclusion body myositis as a distinct entity has further refined nosographic
      classification.

PMID- 14732634
TI  - Gottfried Benn, a German poet-physician, on epilepsy in 1910-1911.

PMID- 14732635
TI  - Cat-scratch encephalopathy.

PMID- 14732636
TI  - POEMS syndrome, fibrinogen, and ischemic stroke: a critical point of view.

PMID- 14732637
TI  - Deep-plane face-lift vs superficial musculoaponeurotic system plication face
      lift: a comparative study.
AB  - OBJECTIVE: To evaluate deep-plane face-lift vs superficial musculoaponeurotic
      system (SMAS) plication face-lift in correcting the melolabial fold, jowl, and
      cheek areas of the face in short-term follow-up. DESIGN: Masked, randomized
      review by 4 board-certified facial plastic surgeons experienced in rhytidectomy
      of full-face (frontal, oblique, and lateral views) before-and-after photographs
      of 20 patients who underwent deep-plane face-lift and 20 who underwent SMAS
      plication face-lift. Participants rated the melolabial fold, jowl, and cheek
      areas for overall correction of the deformities pertaining to the aesthetic
      results for deep-plane vs SMAS plication face-lift. Categories were excellent,
      good, average, acceptable, and poor. RESULTS: Three categories of results were
      determined: best, average, and poorest. Overall, SMAS plication face-lifts scored
      higher than deep-plane face-lifts. In the best category, there were more SMAS
      plication face-lifts. In the average category, there were more deep-plane face
      lifts. In the poorest category, there were equal numbers of deep-plane and SMAS
      face-lifts. Patients were divided into the following age groups: 50 to 59, 60 to
      69, and 70 to 80 years. In the 2 younger groups, SMAS face-lifts scored higher
      than deep-plane face-lifts. In the oldest group, deep-plane face-lifts scored
      slightly higher than SMAS face-lifts. CONCLUSION: Deep-plane face-lift does not
      seem to offer superior results over SMAS plication face-lift in patients younger
      than 70 years.

PMID- 14732638
TI  - Is deep-plane face-lift better than superficial musculoaponeurotic system
      plication face-lift?

PMID- 14732639
TI  - Scalp and forehead reconstruction using free revascularized tissue transfer.
AB  - OBJECTIVE: To examine the indications for, and the success of, free flap
      reconstruction in patients with forehead and scalp defects. DESIGN: Case series.
      SETTING: Two tertiary referral university teaching hospitals. Patients Twenty-six
      consecutive patients, aged 31 to 85 years, presenting with 26 scalp defects, 5
      forehead defects, and 1 combined defect (size, 70-672 cm(2)). Three patients
      required resection and repair of the dura at surgery. Intervention Patients were
      staged according to the size of the defect and the viability of surrounding
      tissue; free flap reconstruction was performed where indicated. MAIN OUTCOME
      MEASURES: Flap survival, complications, and disease-free and overall survival.
      RESULTS: Thirty-four free flap reconstructions were performed (24 latissimus
      dorsi free flaps, 4 scapular free flaps, 3 rectus abdominis free flaps, and 3
      radial forearm free flaps). One failed 2 weeks postoperatively, and 2 required
      exploration (1 for arterial ischemia and 1 for a hematoma). There were 3 cases of
      donor site morbidity (2 early seromas and 1 late abdominal hernia). One patient
      died of a pulmonary embolus 1 week postoperatively. Disease-free survival was 48%
      at 5 years and overall survival was 59% at 5 years, with a median follow-up of 24
      months. CONCLUSIONS: Free revascularized tissue transfer is a reliable and safe
      way of reconstructing large scalp or forehead defects after traumatic injury or
      neoplastic resection. The muscle-only latissimus dorsi free flap for scalp
      reconstruction and the cutaneous scapular free flap for the forehead have proved
      successful in selected patients with a low complication rate and satisfactory
      cosmesis.

PMID- 14732640
TI  - Histomorphologic changes in aging skin: observations in the CBA mouse model.
AB  - BACKGROUND: Aging of human skin is a phenomenon resulting from a combination of
      chronological aging and environmental stressors such as sunlight. OBJECTIVES: To
      study the effects of intrinsic aging on the skin in laboratory-raised CBA mice in
      3 age groups, and to assess histological alterations as a function of age in this
      model. METHODS: Skin samples from CBA mice in 3 age groups (young, young adult,
      and old) were obtained from the dorsal and ventral areas, pinna, and hind foot to
      study the following variables using light microscopic manual morphometric
      methods: the depth of the epidermis and number of epidermal cells, depth of the
      dermis, and percentage area of dermal collagen, elastic fibers, pilosebaceous
      units, blood vessels, and tissue space. The obtained values were analyzed using 1
      way analysis of variance to detect any significant effects of age. RESULTS: There
      was a notable attrition of the epidermal thickness and number of cells that could
      be correlated with age. A reduced number of pilosebaceous units was noted in skin
      samples from the dorsal region and the footpad. No conspicuous change was noted
      in the depth of the dermis or percentage area of collagen in aging animals. A
      proliferation of stainable elastic fibers was demonstrated in the dorsal skin and
      footpad of older mice. CONCLUSIONS: CBA mice show unique age-related histological
      modifications of the skin that are different from other rodent species. These
      baseline data will be helpful in further studies of regenerative effects of
      pharmaceutical agents on the histological structure of skin and in photoaging
      studies.

PMID- 14732641
TI  - Informed consent in facial plastic surgery: effectiveness of a simple educational
      intervention.
AB  - OBJECTIVE: To evaluate the effectiveness of oral communication about the risks of
      facial cosmetic procedures compared with oral and written communication. DESIGN:
      A prospective randomized study conducted in an ambulatory surgery center. One
      hundred twenty consecutive patients were included; they presented for
      consultation for rhinoplasty, rhytidectomy, or laser resurfacing. Patients were
      randomly assigned to 1 of 2 groups: (1) those receiving oral discussion of the
      risks of the procedure and (2) those receiving oral and written communication
      about the risks. Two weeks after the initial consultation, patients were surveyed
      for recall of the risks. RESULTS: The group that received a pamphlet had a better
      risk recall than the group that did not (2.5 vs1.5 of 5 risks; P<.001). The
      recall rate in the following groups that received a pamphlet was also better: (1)
      university-educated patients (P =.02), (2) patients who underwent rhinoplasty
      (P<.001), (3) patients who underwent laser resurfacing (P =.02), and (4) female
      patients (P<.001). CONCLUSIONS: Written disclosure of the risks of cosmetic
      procedures enables patients to retain and understand more clearly those potential
      risks. They are, therefore, able to give an informed consent to the proposed
      procedure. This study also identifies patient groups who may require more
      intensive presurgical teaching. The medicolegal implications are apparent.

PMID- 14732642
TI  - Effect of hyperbaric oxygen on the growth factor profile of fibroblasts.
AB  - OBJECTIVES: Hyperbaric oxygen (HBO) has been used in the clinical setting to heal
      problem wounds, yet its direct effects on fibroblasts are not clear. The present
      study evaluates the effects of HBO on the growth and autocrine production of
      growth factors by fibroblasts grown in an in vitro, serum-free environment.
      METHODS: Human dermal fibroblasts were propagated in serum-free media and
      subjected to daily 90-minute HBO treatments at 1.0, 1.5, 2.0, 2.5, and 3.0 atm of
      pressure for 7 consecutive days. Cell proliferation and growth-factor assays for
      basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF),
      and transforming growth factor beta1 (TGF-beta1) were performed on days 1, 3, 5,
      and 7. RESULTS: On day 1, HBO inhibited growth of fibroblasts at all atmospheric
      pressures compared with control. By day 7, cell proliferation was significantly
      enhanced only in cells treated with 2.0-atm HBO compared with controls. Secretion
      of bFGF was significantly increased by HBO-treated fibroblasts on day 1; VEGF
      levels slightly increased with HBO treatment on day 1, but this effect was not
      statistically significant; TGF-beta1 levels were detectable on day 1 only for
      control and HBO-treated cells at 1.0 atm, and not detectable for any cell groups
      after day 1. CONCLUSIONS: These results suggest that daily HBO treatment enhances
      the growth of fibroblasts when administered to a critical degree. Also, HBO
      appears to directly effect fibroblast production of autocrine growth factors on
      initial exposure. We postulate that fibroblasts possess the ability to respond to
      hyperoxia directly, which causes changes in cell signaling pathways involved in
      cellular proliferation and growth factor production.

PMID- 14732643
TI  - Endonasal spreader graft placement as treatment for internal nasal valve
      insufficiency: no need to divide the upper lateral cartilages from the septum.
AB  - OBJECTIVE: To describe and evaluate results of a surgical procedure to treat
      internal nasal valve insufficiency with the use of spreader grafts placed via an
      endonasal approach without division of the upper lateral cartilages from the
      nasal septum. DESIGN: Eighty-nine patients with complaints of nasal obstruction,
      at least partially due to internal nasal valve insufficiency, underwent this
      operation on 120 sides in a private practice setting. Only autologous material
      was used, and 3 different techniques for fixating the grafts were evaluated. All
      patients were prospectively studied, and subjective self-assessment was used to
      quantify the result of the operation. RESULTS: On 53 sides (44%) nasal breathing
      was described as "optimal," and on 53 sides (44%) the result was deemed
      "improved." On 13 sides (11%) no change was noted, and on 1 side (1%) the
      postoperative situation was judged to be worse. CONCLUSIONS: When opting for
      spreader grafts to treat internal nasal valve insufficiency, one does not
      necessarily need to perform an external approach, nor is separation of the upper
      lateral cartilages from the septum required. The endonasal technique presented
      herein is less invasive and can be used in conjunction with other procedures
      aimed at improving nasal patency.

PMID- 14732644
TI  - Management of the wide nasal dorsum.
AB  - The literature is replete with discussions outlining surgical techniques for
      managing nasal tip deformities. In contrast, articles devoted to specific dorsal
      nasal abnormalities are rare. Surgical management of the nasal dorsum has
      traditionally been relegated to either augmentation or reduction followed by
      osteotomy. Contemporary rhinoplasty demands attention to the creation of an ideal
      profile line, which may require dorsal reduction in some areas and augmentation
      in others. Treatment of the patient with an appropriate projection of the profile
      but with a wide nasal dorsum presents a special challenge: to narrow the nasal
      bridge without altering its projection. We discuss several surgical techniques to
      narrow the nasal dorsum, while maintaining dorsal height. Selected cases are
      presented to illustrate these techniques and to clarify surgical options.

PMID- 14732645
TI  - Refinement in reanimation of the lower face.
AB  - Both the temporalis muscle transfer and the static sling procedure are techniques
      that improve deglutition, speech, and aesthetics in patients who are afflicted
      with paralysis of the lower part of the face. A refinement that is applicable to
      either of these procedures is described. By bringing the perioral attachment of
      either the muscle or the static sling exactly to the midline of the upper and
      lower lips, the surgeon can make the patient's mouth more symmetrical. This
      simple refinement will improve the results obtained with either procedure and has
      not been associated with any increased perioperative risks or complications.

PMID- 14732646
TI  - Reconstruction of complex scalp defects: the "Banana Peel" revisited.
AB  - OBJECTIVE: To demonstrate the use of multiple, large, local flaps in the
      reconstruction of large scalp defects. METHODS: A retrospective review of 4 cases
      in which the "banana peel" method of scalp reconstruction, originally described
      by Orticochea, was used as a method for closure of moderately large to extensive
      scalp defects. RESULTS: In all 4 cases, closure of the scalp defects was
      accomplished. Major morbidity included hair-bearing skin in the forehead in 1
      patient, an inconsequential small flap dehiscence requiring closure in the same
      patient, and a partial loss of a small skin graft to a donor site defect in 1
      patient. CONCLUSIONS: While other techniques may be optimal for the management of
      most scalp defects, such as 1- to 2-flap rotation-advancement flaps in small to
      moderate-size defects and microvascular free tissue transfer and secondary tissue
      expansion for larger defects, we conclude that the multiple-flap reconstruction
      method as described by Orticochea may be useful in a small subset of patients.
      The latter includes older, severely debilitated patients who would be optimally
      treated with microvascular tissue transfer but cannot tolerate lengthy general
      anesthesia and young patients who will not accept a significant area of alopecia
      that might exist with other techniques, such as secondary intention, skin grafts,
      or free flaps.

PMID- 14732647
TI  - Informed consent for rhytidectomy: a survey of AAFPRS fellowship programs.

PMID- 14732648
TI  - Informed consent in facial plastic surgery.

PMID- 14732649
TI  - Orbital volume augmentation for late enophthalmos.

PMID- 14732650
TI  - Edward Talbot Ely: father of aesthetic otoplasty.

PMID- 14732653
TI  - Lost beauty and The Fountain of Youth.

PMID- 14732654
TI  - Intravenous cidofovir for recalcitrant verruca vulgaris in the setting of HIV.

PMID- 14732655
TI  - Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular
      basal cell carcinoma: results of a multicenter randomized prospective trial.
AB  - BACKGROUND: Photodynamic therapy (PDT) is increasingly used as a noninvasive
      treatment for nodular basal cell carcinoma (BCC), without a sound evidence base.
      OBJECTIVE: To compare topical PDT, with the use of the sensitizer methyl
      aminolevulinate, and standard excision surgery in nodular BCC. DESIGN:
      Prospective, randomized study. SETTING: University dermatology departments.
      PATIENTS: A total of 101 adults with previously untreated nodular BCC.
      INTERVENTIONS: Patients received methyl aminolevulinate PDT (n = 52) or surgery
      (n = 49). The PDT was given twice, 7 days apart, with methyl aminolevulinate
      cream (160 mg/g) and 75 J/cm(2) red light (570-670 nm). Thirteen patients with a
      noncomplete response to PDT at 3 months (24% lesions) were retreated. OUTCOME
      MEASURES: Primary end point was clinically assessed lesion clearance at 3 months
      after treatment. Secondary end points were sustained response rate at 12 months
      and cosmetic outcome at 3 and 12 months. Cosmesis and lesion recurrence were
      further assessed at 24 months. RESULTS: Data from 97 patients (105 lesions) were
      included in the 3-month per-protocol analysis. Complete response rates did not
      differ significantly between groups (51/52 [98%] lesions with surgery vs 48/53
      [91%] lesions with methyl aminolevulinate PDT; difference [95% confidence
      interval], 4.8% (-3.4% to 13.0%]; P =.25). At 12 months, tumor-free rates were 50
      (96%) of 52 lesions with surgery vs 44 (83%) of 53 with methyl aminolevulinate
      PDT (P =.15). More patients treated with methyl aminolevulinate PDT than surgery
      had an excellent or good cosmetic outcome at all time points (significant at 12
      and 24 months on patient assessment, P<.05, and at 3, 12, and 24 months on
      investigator evaluation, P<.001). At 24 months, 5 lesions that had initially
      cleared with methyl aminolevulinate PDT had recurred, compared with 1 after
      surgery. CONCLUSIONS: Methyl aminolevulinate PDT is an effective treatment for
      nodular BCC, and while there is a trend for higher recurrence with this modality,
      it conveys the advantage over surgery of better cosmesis.

PMID- 14732656
TI  - Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and
      red light-emitting diodes: two-year results evaluating tumor response and
      cosmetic outcomes.
AB  - BACKGROUND: Efficient treatment of patients with multiple synchronous nonmelanoma
      skin cancers represents a therapeutic challenge. OBJECTIVE: To study the safety
      and efficacy of photodynamic therapy (PDT) with verteporfin and red light in the
      treatment of multiple nonmelanoma skin cancers. DESIGN: Open-label, randomized,
      multicenter, dose-ranging phase 2 study conducted at 4 North American university
      based dermatology clinics. PATIENTS: Fifty-four patients with 421 multiple
      nonmelanoma skin cancers including superficial and nodular basal cell carcinoma
      and squamous cell carcinoma in situ (Bowen disease). METHODS: A single
      intravenous infusion of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by
      exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688 +/- 10 nm) from a
      light-emitting diode panel. MAIN OUTCOME MEASURES: Pathologic response of treated
      sites was assessed at 6 months. Clinical and cosmetic responses were assessed and
      graded at 6 weeks, 3 months, and 6 months after verteporfin PDT, with optional
      follow-up visits at 12, 18, and 24 months. RESULTS: The histopathologic response,
      defined as absence of tumor on biopsy specimens 6 months after verteporfin PDT,
      ranged from 69% at 60 J/cm(2) to 93% at 180 J/cm(2). At 24 months of follow-up
      (276 tumors in 31 patients), the clinical complete response rate ranged from 51%
      at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were
      observed; most events occurred at the treated tumor sites and included events
      such as pain. Overall, 65% (95% confidence interval, 58%-71%) of tumors were
      judged to have good to excellent cosmesis at 24 months. CONCLUSION: A single
      course of verteporfin PDT showed treatment benefit for patients with multiple
      nonmelanoma skin cancers.

PMID- 14732657
TI  - A trial of short incubation, broad-area photodynamic therapy for facial actinic
      keratoses and diffuse photodamage.
AB  - BACKGROUND: There is no completely satisfactory treatment for multiple actinic
      keratoses (AKs). OBJECTIVE: To evaluate the efficacy of short incubation, broad
      area application of delta-aminolevulinic acid followed by exposure to activating
      light-photodynamic therapy (delta-ALA/PDT) for treatment of AKs and background
      photodamage. The benefit of pretreatment with 40% urea cream to enhance
      penetration and the use of topical 3% lidocaine hydrochloride to decrease
      discomfort were also evaluated. METHODS: Eighteen patients with at least 4
      nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage were
      enrolled in the study. For 7 days, 40% urea cream or vehicle was applied to half
      of the treatment area, and then delta-ALA was applied to the entire area for 1,
      2, or 3 hours. Lidocaine hydrochloride (3%) or vehicle cream was also applied to
      the entire area 45 minutes before exposure to 10 J/cm(2) of blue light.
      Pain,phototoxic reactions, AK counts, and photodamage improvement were evaluated
      1 day, 1 week, and 1 month after treatment in all patients and after 5 months in
      10 patients. RESULTS: All patients experienced mild to moderate discomfort during
      treatment and moderate phototoxic effects for 1 week. At 1 and 5 months there was
      significant reduction in AKs in all groups and significant improvement of several
      photodamage parameters. Different delta-ALA application times and pretreatment
      with urea cream or lidocaine had no significant effect on the results.
      CONCLUSIONS: This delta-ALA/PDT protocol is safe and effective for AK treatment
      as well as for improving photodamage. Further studies with a larger cohort,
      longer follow-up, and histologic confirmation of the clinical data would be of
      value.

PMID- 14732659
TI  - Photodynamic therapy with aminolevulinic acid topical solution and visible blue
      light in the treatment of multiple actinic keratoses of the face and scalp:
      investigator-blinded, phase 3, multicenter trials.
AB  - OBJECTIVE: To determine the safety and efficacy of photodynamic therapy (PDT)
      using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter "ALA") and
      visible blue light for the treatment of multiple actinic keratoses of the face
      and scalp. DESIGN: Randomized, placebo-controlled, uneven parallel-group study.
      INTERVENTIONS: Patients (N = 243) were randomized to receive vehicle or ALA
      followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1,
      4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re
      treated. MAIN OUTCOME MEASURE: Clinical response based on lesion clearing by week
      8. RESULTS: Most patients in both groups had 4 to 7 lesions. Complete response
      rates for patients with 75% or more of the treated lesions clearing at weeks 8
      and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and
      18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran
      Mantel-Haenszel general association test). The 95% confidence interval for the
      difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3%
      to 86.3%. The week 12 response rate includes 30% of patients who received a
      second treatment. Most patients experienced erythema and edema at the treated
      sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging
      or burning during light treatment, which decreased or resolved by 24 hours after
      light treatment. CONCLUSION: Findings indicate that topical ALA PDT is an
      effective and safe treatment for multiple actinic keratoses of the face and
      scalp.

PMID- 14732660
TI  - Digital epiluminescence microscopy monitoring of high-risk patients.
AB  - OBJECTIVE: To examine the outcome of digital epiluminescence microscopic (DELM)
      surveillance of atypical nevi in a high-risk population for 4 years. DESIGN:
      Atypical, flat melanocytic lesions in 100 patients at high risk of developing
      melanoma were followed annually with DELM. Pigmentary changes or an increase in
      DELM diameter of 1 mm or greater was an indication to perform an excisional
      biopsy. SETTING: Cardinal Bernardin Cancer Center Melanoma Program, Loyola
      University Health System, Maywood. PATIENTS: A consecutive sample of 3482 lesions
      from 100 patients (aged 18-65 years) with at least 2 images of the same lesion.
      MAIN OUTCOME MEASURES: The DELM change was confirmed by histopathologic
      examination. Patient confidence in and comfort with dermatologic surveillance and
      skin self-examination performance were assessed. RESULTS: During annual
      surveillance with DELM, 5.5% of the lesions changed. Among the 193 excisional
      biopsy specimens there were 4 melanomas in situ, 169 dysplastic nevi, and 20
      common nevi. Confidence in and comfort with surveillance and skin self
      examination improved after DELM. CONCLUSIONS: The criteria applied to detect
      substantial DELM changes were an increase in DELM diameter of 1 mm or greater and
      pigmentary changes, including radial streaming, focal enlargement, peripheral
      black dots, and "clumping" within the irregular pigment network. Use of DELM
      enhanced confidence in and comfort with care, which extended to performing more
      extensive skin self-examination.

PMID- 14732661
TI  - Diagnostic accuracy of patients in performing skin self-examination and the
      impact of photography.
AB  - OBJECTIVE: To determine the sensitivity and specificity of skin self-examination
      (SSE) to detect new and changing moles with and without the aid of baseline
      digital photographs in patients with dysplastic nevi. DESIGN AND INTERVENTION:
      Patients had baseline digital photography and mole counts of their back, chest,
      and abdomen and were instructed to perform a baseline SSE. Print copies of the
      images were provided to the patient. Following the baseline examination, the
      appearance of existing moles was altered and new moles were created using
      cosmetic eyeliner. The number of moles altered and/or created totaled
      approximately 10% of each patients' absolute mole count. SETTING AND PATIENTS:
      Fifty patients with 5 or more dysplastic nevi from the outpatient clinic at
      Memorial Sloan-Kettering Cancer Center, New York, NY. MAIN OUTCOME MEASURE: Skin
      self-examinations with and without access to the baseline photographs to identify
      the number of new and altered moles. RESULTS: The sensitivity and specificity of
      SSE for detection of both altered and new moles without photography were 60.2%
      and 96.2%, respectively. Skin self-examination with photography yielded a
      sensitivity and specificity of 72.4% and 98.4%, respectively. The findings were
      similar when stratified by site (back vs chest or abdomen). The sensitivity and
      specificity for new moles were higher compared with altered moles. CONCLUSIONS:
      Access to baseline photography improved the diagnostic accuracy of SSE on the
      back and chest or abdomen and improved detection of changing and new moles. Our
      results suggest that baseline digital photography in tandem with SSE may be
      effective in improving the diagnostic accuracy of patients performing SSE.

PMID- 14732662
TI  - Early detection of asymptomatic pulmonary melanoma metastases by routine chest
      radiographs is not associated with improved survival.
AB  - OBJECTIVE: To determine if earlier detection of pulmonary metastasis by routine
      chest radiography (CR) is associated with a prolonged survival. DESIGN: A
      computer-assisted search of all CR reports on patients with melanoma between 1990
      and 1994 at the Massachusetts General Hospital, Boston. Positive or suspicious
      findings for pulmonary metastasis were further pursued through review of medical
      records and tumor registry files. SETTING AND PATIENTS: A hospital-based
      population of patients with melanoma undergoing routine CR at Massachusetts
      General Hospital. RESULTS: Overall, of 994 patients, 75 were identified as having
      pulmonary metastases by CR (1937 total chest radiographs). In addition, there
      were 63 patients with suspicious findings that were later shown to be false
      positive. Chest radiographs provided the initial evidence of metastases in 41
      asymptomatic individuals. Thirty-four patients had known melanoma metastases to
      other sites at the time of the first abnormal chest radiograph. Survival after
      identification of pulmonary metastasis did not differ significantly between the 2
      groups. CONCLUSIONS: In this study, there was no evidence to support the notion
      that earlier detection of pulmonary metastasis in otherwise asymptomatic
      individuals confers a survival advantage in an unselected melanoma population.

PMID- 14732663
TI  - Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy.
AB  - OBJECTIVE: To evaluate the feasibility of sentinel node staging for detection of
      occult regional lymph node metastasis in high-risk cutaneous nonmelanoma
      malignancies. DESIGN: Consecutive clinical case series. SETTING: Referral
      university medical center. PATIENTS: A consecutive sample of patients with a
      variety of high-risk nonmelanoma cutaneous malignancies without evidence of
      regional lymph node metastases. INTERVENTION: Sentinel node biopsies were
      performed using preoperative lymphoscintigraphy, blue dye, and intraoperative
      radiolocalization. MAIN OUTCOME MEASURE: Sensitivity, determined by comparing the
      results of biopsy specimen evaluation with those of completion lymphadenectomy
      and/or clinical follow-up. RESULTS: Twenty-four patients underwent sentinel node
      biopsy for the staging of 29 nodal basins identified by lymphoscintigraphy.
      Primary diagnoses were squamous cell carcinoma (n = 17), Merkel cell carcinoma (n
      = 5), and adenocarcinoma (n = 2). Seven patients (29%) had a tumor-positive
      sentinel node. Sentinel node biopsy followed by complete lymphadenectomy was
      performed in 12 patients and sentinel node biopsy alone in 12 patients. Tumor
      positive lymph nodes were noted in 8 patients, 7 of whom also had positive
      sentinel nodes. There was 1 false-positive result (1/8 [12%]), in a patient with
      recurrent squamous cell carcinoma of the scalp. At a median follow-up of 10
      months, no recurrences in a sentinel node-negative basin have been noted.
      Compared with all information, the sensitivity of sentinel node staging was 88%
      and the negative predictive value was 0.94. CONCLUSIONS: Sentinel node biopsy is
      a minimally invasive staging procedure useful in identifying occult regional
      lymph node disease in selected patients with nonmelanoma cutaneous malignancies.
      Further studies to verify these findings and develop formal guidelines are
      indicated.

PMID- 14732664
TI  - Neonatal giant congenital nevi with proliferative nodules: a clinicopathologic
      study and literature review of neonatal melanoma.
AB  - BACKGROUND: Review of the literature reveals that congenital malignant melanoma
      is an exceptionally rare occurrence and has a generally poor prognosis when it
      does occur. However, benign proliferative melanocytic lesions are known to occur
      within giant congenital nevi (GCN). This entity is not well recognized and can be
      confused clinically and histologically with malignant change. OBSERVATIONS: We
      report 2 cases of GCN in neonates demonstrating benign proliferating nodules
      present at birth. An initial diagnosis of malignant melanoma was assumed in both
      cases. Careful histologic analysis, however, revealed these lesions to be benign,
      as did long-term follow-up of 3.5 years, with both patients remaining well with
      no evidence of melanoma. Review of the literature suggests that there are 2
      clinical patterns of these benign nodules arising within GCNs: small (<1 cm) and
      large (>1 cm) dermal nodules with varying histologic patterns that we have
      attempted to categorize. CONCLUSIONS: Our cases illustrate the difficulty in
      accurate diagnosis of melanocytic lesions in the neonate. We recommend caution in
      making a diagnosis of malignant melanoma and highlight the possibility that
      benign lesions can be mistaken for melanoma in this age group. We encourage the
      acquisition of fixed histologic specimens for accurate diagnosis of melanocytic
      lesions.

PMID- 14732665
TI  - Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal
      antibody).
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a severe antibody-mediated autoimmune
      blistering disease. Because some patients with PV do not enter into remission,
      despite the use of high-dose corticosteroid therapy and immunosuppressive
      adjuvant treatments, new effective and safer agents are warranted to treat
      refractory PV. Rituximab, a monoclonal anti-CD20 antibody, induces depletion of B
      cells in vivo and has shown efficacy in patients with refractory antibody
      mediated autoimmune disorders. We describe herein 3 patients treated with
      rituximab for severe PV. OBSERVATIONS: Three patients with refractory PV were
      treated with rituximab, resulting in a clinical response in all patients, which
      was complete in 2 patients. A decline in titers of circulating antiepidermis
      autoantibodies paralleled disease activity, while circulating B cells remained
      undetectable for 6 to 10 months. Two patients experienced bacterial infection in
      the weeks following the rituximab course. A clinical relapse occurred in 2
      patients, at 6 and 10 months. A second course of rituximab controlled the disease
      in one of them. CONCLUSION: These patients' response suggests that rituximab may
      be a valuable treatment for refractory PV and warrants further studies to
      evaluate the risk-benefit ratio in patients with PV showing resistance to classic
      therapy.

PMID- 14732666
TI  - Primary dermal melanoma: a distinct subtype of melanoma.
AB  - BACKGROUND: The term primary dermal melanoma has been used to describe a subtype
      of melanoma confined to the dermis and/or subcutaneous fat that histologically
      simulates metastasis but is associated with an unexpectedly prolonged survival.
      We report 7 cases of primary dermal melanoma diagnosed from 1998 to 2002 with no
      identifiable junctional or epidermal component or nevoid precursor.
      Histopathologic and immunohistochemical features were compared with known cases
      of cutaneous metastasis and nodular melanoma in an attempt to differentiate this
      entity from clinical and pathologic mimics. OBSERVATIONS: Seven patients had a
      single dermal and/or subcutaneous focus of melanoma. Metastatic staging workup
      findings were negative, including results from sentinel node and imaging studies.
      Mean Breslow depth was 7.0 mm, and mean maximum tumor diameter was 6.2 mm. The
      study cohort showed 100% survival at mean follow-up of 41 months (range, 10-64
      months). Immunohistochemical analysis with S100, HMB-45, Ki-67, CD34, and p75
      antibodies showed no significant staining patterns compared with metastatic and
      nodular melanomas. CONCLUSIONS: Primary dermal melanoma appears to be a distinct
      subtype of melanoma based on the excellent prognosis associated with this case
      series and others. Additional research focusing on cause, appropriate staging,
      and outcome of previously identified solitary dermal metastasis is warranted to
      further delineate this entity.

PMID- 14732667
TI  - Staging workup, sentinel node biopsy, and follow-up tests for melanoma: update of
      current concepts.
AB  - OBJECTIVES: To clarify and update workup and follow-up strategies based on
      fundamental principles and current data, and to discuss new and current concepts
      regarding sentinel lymph node biopsy (SLNB), particularly in relation to the
      staging workup. DATA SOURCES: Studies conducted from 1995 to 2003 were identified
      by PubMed search. Additional searches included workup for reference lists of
      retrieved articles when applicable, and PubMed-related articles. STUDY SELECTION:
      Contemporary studies with good design, conclusions based on sound methods, and
      results pertaining to staging workup, SLNB, and follow-up tests were critically
      reviewed. DATA EXTRACTION: Data and conclusions based on the above studies were
      incorporated into a review. DATA SYNTHESIS: Routine tests have marginal to no
      efficacy and are not cost-efficient for detecting occult disease in asymptomatic
      patients with localized melanoma. The only staging test that has relatively high
      sensitivity and specificity and provides tissue diagnosis is SLNB; moreover, SLNB
      has revolutionized our understanding of lymphatic pathways. The concepts of
      interval nodes and unexpected lymphatic drainage pathways have been addressed by
      several recent reports. There are no data that demonstrate any significant
      difference in overall survival for detection of asymptomatic vs symptomatic stage
      IV melanoma. CONCLUSIONS: An initial workup is useful for staging and prognosis
      to identify occult disease, with potential outcome benefit if treated early; and,
      by detecting distant occult disease (stage IV), to obviate the need for an
      extensive surgical procedure and thereby avoid associated increased morbidity.
      The foundation for the workup and follow-up remains thorough history taking and a
      physical examination, combined with a low index of suspicion for symptom-directed
      tests.

PMID- 14732668
TI  - The sweep of time for the Archives of Dermatology.

PMID- 14732670
TI  - Photodynamic therapy for nonmelanoma skin cancer--and more?

PMID- 14732671
TI  - Flesh-colored papules on the wrists of a 61-year-old man.

PMID- 14732672
TI  - Warty nodules on an annular plaque in a renal transplant recipient.

PMID- 14732673
TI  - Hypopigmented papules and nodules on the trunk and arms.

PMID- 14732674
TI  - Palmar nodule in a child.

PMID- 14732675
TI  - Risk estimation for malignant transformation of melanocytic nevi.

PMID- 14732676
TI  - "Globulelike" dermoscopic structures in pigmented seborrheic keratosis.

PMID- 14732677
TI  - Favre-Racouchot disease provoked by UV-A1 and UV-B exposure.

PMID- 14732678
TI  - Dermoscopy of melanocytic neoplasms: subpatterns of dysplastic/atypical nevi.

PMID- 14732680
TI  - Histone H3.3 is enriched in covalent modifications associated with active
      chromatin.
AB  - Chromatin states can be distinguished by differential covalent modifications of
      histones or by utilization of histone variants. Chromatin associated with
      transcriptionally active loci becomes enriched for histones with particular
      lysine modifications and accumulates the H3.3 histone variant, the substrate for
      replication-independent nucleosome assembly. However, studies of modifications at
      particular loci have not distinguished between histone variants, so the
      relationship among modifications, histone variants, and nucleosome assembly
      pathways is unclear. To address this uncertainty, we have quantified the relative
      abundance of H3 and H3.3 and their lysine modifications. Using a Drosophila cell
      line system in which H3.3 has been shown to specifically package active loci, we
      found that H3.3 accounts for approximately 25% of total histone 3 in bulk
      chromatin, enough to package essentially all actively transcribed genes. MS and
      antibody characterization of separated histone 3 fractions revealed that H3.3 is
      relatively enriched in modifications associated with transcriptional activity and
      deficient in dimethyl lysine-9, which is abundant in heterochromatin. To explain
      enrichment on alternative variants, we propose that histone modifications are
      tied to the alternative nucleosome assembly pathways that use primarily H3 at
      replication forks and H3.3 at actively transcribed genes in a replication
      independent manner.

PMID- 14732681
TI  - Mutations arising in the wave front of an expanding population.
AB  - The ability to infer the time and place of origin of a mutation can be very
      useful when reconstructing the evolutionary histories of populations and species.
      We use forward computer simulations of population growth, migration, and mutation
      in an analysis of an expanding population with a wave front that advances at a
      constant slow rate. A pronounced founder effect can be observed among mutations
      arising in this wave front where extreme population bottlenecks arise and are
      followed by major population growth. A fraction of mutations travel with the wave
      front and generate mutant populations that are on average much larger than those
      that remain stationary. Analysis of the diffusion of these mutants makes it
      possible to reconstruct migratory trajectories during population expansions, thus
      helping us better understand observed patterns in the evolution of species such
      as modern humans. Examination of some historical data supports our model.

PMID- 14732682
TI  - Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic
      signaling.
AB  - Members of the Bcl-2 protein family that share only the Bcl-2 homology 3 (BH3)
      domain are known mostly as sentinels for apoptotic stimuli and initiators of
      apoptosis. One BH3-only protein, Bim, is the major physiological antagonist of
      the prosurvival proteins in B and T lymphocytes. It is required for hematopoietic
      homeostasis and to preclude autoimmunity. Here, we show that the Bim(EL) isoform,
      which was predominant in T cells, existed in both phosphorylated and
      unphosphorylated forms. Whereas the unphosphorylated Bim(EL) was sequestered to
      microtubules by means of a direct interaction with tubulin, the phosphorylated
      protein was released from microtubules. The freed Bim(EL) was subjected to
      caspase cleavage at an early stage of apoptosis induced by stimuli that activate
      either the mitochondria- or death receptor-dependent apoptosis pathway. The N
      terminally cleaved Bim(EL) became hyperactive in inducing apoptosis because of
      its more efficient targeting of Bcl-2. Thus, unlike many other BH3-only proteins,
      Bim(EL) can be activated downstream of the caspase cascade, leading to a positive
      feedback amplification of apoptotic signals.

PMID- 14732683
TI  - Simian virus 40 large T antigen targets the spindle assembly checkpoint protein
      Bub1.
AB  - The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low
      frequency in certain human cancers characterized by aneuploidy. Simian virus 40
      large T antigen efficiently immortalizes rodent cells and occasionally transforms
      them to tumorigenicity. T antigen can also cause genomic instability, inducing
      chromosomal aberrations and aneuploidy. Here, we report an interaction between
      Bub1 and T antigen. T antigen coimmunoprecipitates with endogenous Bub1 and Bub3,
      another component of the spindle checkpoint complex. Genetic analysis
      demonstrates that the interaction of T antigen with Bub1 is not required for
      immortalization but is closely correlated with transformation. T antigen induces
      an override of the spindle checkpoint dependent on Bub1 binding. This interaction
      with proteins of the spindle checkpoint machinery suggests another role for T
      antigen and provides insight into its ability to cause chromosomal aberrations,
      aneuploidy, and transformation.

PMID- 14732684
TI  - A feedback mechanism regulates monoallelic odorant receptor expression.
AB  - In olfactory neurons, expression of a single odorant receptor (OR) from a
      repertoire of >1000 genes is required for odor coding and axonal targeting. Here,
      we demonstrate a role for OR protein as an essential regulator in the
      establishment of monoallelic OR expression. An OR-promoter-driven reporter
      expresses in a receptor-like pattern but, unlike a native OR, is coexpressed with
      an additional OR allele. Expression of a functional OR from the identical
      promoter eliminates expression of other OR alleles. The presence of an
      untranslatable OR coding sequence in the mRNA is insufficient to exclude
      expression of a second OR. Together, these data identify the OR protein as a
      critical element in a feedback pathway that regulates OR selection.

PMID- 14732685
TI  - Evidence for complex, collective dynamics and emergent, distributed computation
      in plants.
AB  - It has been suggested that some biological processes are equivalent to
      computation, but quantitative evidence for that view is weak. Plants must solve
      the problem of adjusting stomatal apertures to allow sufficient CO(2) uptake for
      photosynthesis while preventing excessive water loss. Under some conditions,
      stomatal apertures become synchronized into patches that exhibit richly
      complicated dynamics, similar to behaviors found in cellular automata that
      perform computational tasks. Using sequences of chlorophyll fluorescence images
      from leaves of Xanthium strumarium L. (cocklebur), we quantified spatial and
      temporal correlations in stomatal dynamics. Our values are statistically
      indistinguishable from those of the same correlations found in the dynamics of
      automata that compute. These results are consistent with the proposition that a
      plant solves its optimal gas exchange problem through an emergent, distributed
      computation performed by its leaves.

PMID- 14732686
TI  - Direct interactions between Epstein-Barr virus leader protein LP and the EBNA2
      acidic domain underlie coordinate transcriptional regulation.
AB  - The Epstein-Barr virus nuclear leader protein LP (EBNALP) and EBNA2 are expressed
      first in lymphocyte infection, coordinately regulate cell and viral gene
      transcription, and are critical for lymphocyte outgrowth into lymphoblastoid cell
      lines (LCLs). We have now found that EBNALP readily associated with EBNA2 or with
      the EBNA2 C-terminal acidic activation domain (E2AD) when both components were
      expressed by bacteria. In lymphoblasts, EBNALP and EBNA2 did not stably
      associate. However, EBNALP deleted for only 10 C-terminal amino acids stably
      associated with EBNA2 in lymphoblasts or with EBNA2 acidic activating domain from
      bacteria. The E2AD was essential for EBNALP coactivation of the latent membrane
      protein 1 promoter in lymphoblasts; EBNALP could coactivate with a deficient
      mutant EBNA2, EBNA2W(454)T, but not with EBNA2 deleted for E2AD. Moreover, EBNALP
      31 amino acids (dW2Y1) with 24 C- or N-terminal amino acids was a specific and
      efficient affinity matrix for EBNA2 or EBNALP. Even an EBNALP 22-aa peptide, dW2,
      specifically bound EBNALP or EBNA2. These biochemical interactions between EBNALP
      and EBNA2 enable coordinated transcriptional regulation of cell and viral gene
      expression in lymphoblasts only when the interaction is unstable; deletion of the
      EBNALP C-terminal 10 aa stabilized association with EBNA2 and prevented
      coactivation. Because EBNALPd10 dominantly inhibited EBNALP coactivation with
      EBNA2, EBNALPd10 expression in LCLs may be useful in assessing the role of EBNALP
      coactivation in LCL growth or survival.

PMID- 14732687
TI  - A subterranean mammal uses the magnetic compass for path integration.
AB  - Path integration allows animals to navigate without landmarks by continuously
      processing signals generated through locomotion. Insects such as bees and ants
      have evolved an accurate path integration system, assessing and coding rotations
      with the help of a general directional reference, the sun azimuth. In mammals, by
      contrast, this process can take place through purely idiothetic (mainly
      proprioceptive and vestibular) signals. However, without any stable external
      reference for measuring direction, path integration is highly affected by
      cumulative errors and thus has been considered so far as valid only for short
      distance navigation. Here we show through two path integration experiments
      (homing and shortcut finding) that the blind mole rat assesses direction both
      through internal signals and by estimating its heading in relation to the earth's
      magnetic field. Further, it is shown that the greater the circumvolution and
      length of the traveled path, the more the animal relies on the geomagnetic field.
      This path integration system strongly reduces the accumulation of errors due to
      inaccuracies in the estimation of rotations and thus allows the mole rat to
      navigate efficiently in darkness, without the help of any landmark, over both
      short and long distances.

PMID- 14732688
TI  - Identifying gene regulatory elements by genome-wide recovery of DNase
      hypersensitive sites.
AB  - Analysis of the human genome sequence has identified approximately 25000-30000
      protein-coding genes, but little is known about how most of these are regulated.
      Mapping DNase I hypersensitive (HS) sites has traditionally represented the gold
      standard experimental method for identifying regulatory elements, but the labor
      intensive nature of this technique has limited its application to only a small
      number of human genes. We have developed a protocol to generate a genome-wide
      library of gene regulatory sequences by cloning DNase HS sites. We generated a
      library of DNase HS sites from quiescent primary human CD4(+) T cells and
      analyzed approximately 5600 of the resulting clones. Compared to sequences from
      randomly generated in silico libraries, sequences from these clones were found to
      map more frequently to regions of the genome known to contain regulatory
      elements, such as regions upstream of genes, within CpG islands, and in sequences
      that align between mouse and human. These cloned sites also tend to map near
      genes that have detectable transcripts in CD4(+) T cells, demonstrating that
      transcriptionally active regions of the genome are being selected. Validation of
      putative regulatory elements was achieved by repeated recovery of the same
      sequence and real-time PCR. This cloning strategy, which can be scaled up and
      applied to any cell line or tissue, will be useful in identifying regulatory
      elements controlling global expression differences that delineate tissue types,
      stages of development, and disease susceptibility.

PMID- 14732689
TI  - Quantal size fits central synaptic depression.

PMID- 14732690
TI  - The ins and outs of presenilin 1 membrane topology.

PMID- 14732691
TI  - The presenilins turned inside out: implications for their structures and
      functions.
AB  - The presenilin (PS) proteins are polytopic integral membrane proteins that are
      critically involved in the development of Alzheimer's disease. The topography of
      the PS molecule in the endoplasmic reticulum membrane is widely accepted as
      exhibiting eight-hydrophobic-transmembrane (8-TM) helices. We have previously
      provided evidence, however, that the intact PS molecule is also present in the
      cell surface where it exhibits exclusively a 7-TM topography, which differs in
      significant structural features from the 8-TM model. This evidence, however, has
      been disparaged and generally rejected by researchers in Alzheimer's disease. The
      7-TM model is definitively demonstrated in the present study for PS-1 at the
      surfaces of PS-1-transfected cells and for endogenous PS-1 at the surfaces of
      untransfected cells, by immunofluorescence studies using mAbs. These studies
      force substantial revision of current views of the structural and functional
      properties of the PS proteins.

PMID- 14732692
TI  - Insights into the molecular basis for fibroblast growth factor receptor
      autoinhibition and ligand-binding promiscuity.
AB  - The prototypical fibroblast growth factor receptor (FGFR) extracellular domain
      consists of three Ig domains (D1-D3) of which the two membrane-proximal D2 and D3
      domains and the interconnecting D2-D3 linker bear the determinants of ligand
      binding and specificity. In contrast, D1 and the D1-D2 linker are thought to play
      autoinhibitory roles in FGFR regulation. Here, we report the crystal structure of
      the three-Ig form of FGFR3c in complex with FGF1, an FGF that binds promiscuously
      to each of the seven principal FGFRs. In this structure, D1 and the D1-D2 linker
      are completely disordered, demonstrating that these regions are dispensable for
      FGF binding. Real-time binding experiments using surface plasmon resonance show
      that relative to two-Ig form, the three-Ig form of FGFR3c exhibits lower affinity
      for both FGF1 and heparin. Importantly, we demonstrate that this autoinhibition
      is mediated by intramolecular interactions of D1 and the D1-D2 linker with the
      minimal FGF and heparin-binding D2-D3 region. As in the FGF1-FGFR2c structure,
      but not the FGF1-FGFR1c structure, the alternatively spliced betaC'-betaE loop is
      ordered and interacts with FGF1 in the FGF1-FGFR3c structure. However, in
      contrast to the FGF1-FGFR2c structure in which the betaC'-betaE loop interacts
      with the beta-trefoil core region of FGF1, in the FGF1-FGFR3c structure, this
      loop interacts extensively with the N-terminal region of FGF1, underscoring the
      importance of the FGF1 N terminus in conferring receptor-binding affinity and
      promiscuity. Importantly, comparison of the three FGF1-FGFR structures shows that
      the flexibility of the betaC'-betaE loop is a major determinant of ligand-binding
      specificity and promiscuity.

PMID- 14732693
TI  - The tethered configuration of the EGF receptor extracellular domain exerts only a
      limited control of receptor function.
AB  - Quantitative epidermal growth factor (EGF)-binding experiments have shown that
      the EGF-receptor (EGFR) is displayed on the surface of intact cells in two forms,
      a minority of high-affinity and a majority of low-affinity EGFRs. On the basis of
      the three-dimensional structure of the extracellular ligand binding domain of the
      EGFR, it was proposed that the intramolecularly tethered and autoinhibited
      configuration corresponds to the low-affinity receptor, whereas the extended
      configuration accounts for the high-affinity EGFRs on intact cells. Here we test
      this model by analyzing the properties of EGFRs mutated in the specific regions
      responsible for receptor autoinhibition and dimerization, respectively. Our
      results show that mutagenic disruption of the autoinhibitory tether in EGFR
      results in a decrease in the dissociation rate of EGF without a detectable change
      in EGFR activation and signaling through EGFR even in response to stimulation
      with low concentrations of EGF. Mutagenic disruption of the dimerization arm, on
      the other hand, increased the rate of EGF dissociation and impaired EGFR
      activation and signaling via the EGFR. This study demonstrates that the extended
      configuration of EGFR does not account for the apparent high-affinity EGF-binding
      to EGFR on intact cells. Furthermore, the autoinhibition conferred by the
      tethered configuration of the extracellular ligand-binding domain provides only a
      limited control of EGFR function.

PMID- 14732694
TI  - A structure-based model for ligand binding and dimerization of EGF receptors.
AB  - On the basis of the 3D structures of the extracellular ligand-binding domains of
      the epidermal growth factor (EGF) receptor (EGFR) and ErbB3, a mechanism has been
      proposed for how the extracellular region of the EGFR is maintained in an
      autoinhibited configuration and for how EGF binding induces EGFR dimerization and
      activation. We have attempted to derive a mathematical model for EGF binding to
      the EGFR and for ligand-induced receptor dimerization and activation that uses
      this structural information and can explain the characteristic concave-up
      curvilinear Scatchard plots seen when EGF binding to intact EGFR is studied in
      living cells. We show that these curvilinear plots cannot be accounted for by
      simply ascribing different affinities to the autoinhibited and extended (dimeric)
      configurations of the receptor seen in structural studies. Concave-up plots can
      only be obtained by including in the mathematical model an additional binding
      event in which occupied EGFR dimers bind to an "external site." The external site
      may represent receptor interactions with coated-pit regions in the cell membrane
      or with other cellular components involved in receptor endocytosis and turnover.
      We conclude in this study and in the accompanying article that the active
      extended EGFR configuration binds EGF 5- to 20-fold more strongly than the
      autoinhibited monomeric receptor configuration. However, these extended receptors
      do not correspond directly with the "high-affinity" EGF-binding sites seen in EGF
      binding studies on intact cells.

PMID- 14732695
TI  - A role for p300/CREB binding protein genes in promoting cancer progression in
      colon cancer cell lines with microsatellite instability.
AB  - Our manipulation of the nonsense-mediated decay pathway in microsatellite
      unstable colon cancer cell lines identified the p300 gene as a potential tumor
      suppressor in this subtype of cancer. Here, we have demonstrated that not only
      the p300 gene but also the highly homologous cAMP-response element-binding
      protein (CREB) binding protein (CBP) gene together are mutated in >85% of
      microsatellite instability (MSI)+ colon cancer cell lines. A limited survey of
      primary tumors with MSI+ shows that p300 is also frequently mutated in these
      cancers, demonstrating that these mutations are not consequences of in vitro
      growth. The mutations in both genes occur frequently in mononucleotide repeats
      that generate premature stop codons. Reintroduction of p300 into MSI colon cancer
      cells could only be supported in the presence of an inactivated CBP gene,
      suggesting the idea that one or the other function must be inactivated for cancer
      cell viability. p300 is known to acetylate p53 in response to DNA damage, and
      when MSI+ cells null for p300 activity are forced to reexpress exogenous p300
      cells show slower growth and a flatter morphology. p53 acetylation is increased
      upon reexpression of p300, suggesting that MSI+ cells constitutively activate the
      DNA damage response pathway in the absence of DNA-damaging agents. In support of
      this hypothesis, c-ABL kinase, which is also activated in response to DNA damage,
      shows higher levels of basal kinase activity in MSI+ cells. These observations
      suggest that there is a selective growth/survival advantage to mutational
      inactivation of p300/CBP in cells with inactivated mismatch repair capabilities.

PMID- 14732696
TI  - Visualization of spatially and temporally regulated N-WASP activity during
      cytoskeletal reorganization in living cells.
AB  - Members of the WASP/WAVE family of proteins are key regulators of cytoskeletal
      reorganization across a diverse range of cellular processes. Despite a wealth of
      biochemical data about WASP/WAVE regulation in vitro, our understanding of the in
      vivo regulation of these proteins is hampered by the inability to monitor
      subcellular regulation of their activities in living cells. Here we establish a
      fluorescence resonance energy transfer-based approach to visualize spatial and
      temporal regulation of neuronal Wiskott-Aldrich syndrome protein (N-WASP)
      activity in living cells. Using time-lapse microscopy, we characterize the
      activation of N-WASP in response to growth-factor stimulation, and we reveal that
      N-WASP is activated inside extending filopodia. Furthermore, we suggest a role of
      N-WASP in regulating membrane ruffling downstream of phosphatidylinositol 4,5
      bisphosphate and Cdc42.

PMID- 14732697
TI  - The evolution of transmembrane helix kinks and the structural diversity of G
      protein-coupled receptors.
AB  - One of the hallmarks of membrane protein structure is the high frequency of
      transmembrane helix kinks, which commonly occur at proline residues. Because the
      proline side chain usually precludes normal helix geometry, it is reasonable to
      expect that proline residues generate these kinks. We observe, however, that the
      three prolines in bacteriorhodopsin transmembrane helices can be changed to
      alanine with little structural consequences. This finding leads to a conundrum:
      if proline is not required for helix bending, why are prolines commonly present
      at bends in transmembrane helices? We propose an evolutionary hypothesis in which
      a mutation to proline initially induces the kink. The resulting packing defects
      are later repaired by further mutation, thereby locking the kink in the
      structure. Thus, most prolines in extant proteins can be removed without major
      structural consequences. We further propose that nonproline kinks are places
      where vestigial prolines were later removed during evolution. Consistent with
      this hypothesis, at 14 of 17 nonproline kinks in membrane proteins of known
      structure, we find prolines in homologous sequences. Our analysis allows us to
      predict kink positions with >90% reliability. Kink prediction indicates that
      different G protein-coupled receptor proteins have different kink patterns and
      therefore different structures.

PMID- 14732698
TI  - Estimating hydration changes upon biomolecular reactions from osmotic stress,
      high pressure, and preferential hydration experiments.
AB  - How do we estimate, from thermodynamic measurements, the number of water
      molecules adsorbed or released from biomolecules as a result of a biochemical
      process such as binding and allosteric effects? Volumetric and osmotic stress
      analyses are established methods for estimating water numbers; however, these
      techniques often yield conflicting results. In contrast, Kirkwood-Buff theory
      offers a novel way to calculate excess hydration number from volumetric data,
      provides a quantitative condition to gauge the accuracy of osmotic stress
      analysis, and clarifies the relationship between osmotic and volumetric analyses.
      I have applied Kirkwood-Buff theory to calculate water numbers for two processes:
      (i) the allosteric transition of hemoglobin and (ii) the binding of camphor to
      cytochrome P450. I show that osmotic stress analysis may overestimate hydration
      number changes for these processes.

PMID- 14732699
TI  - Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice
      overexpressing the low-density lipoprotein receptor-related protein.
AB  - Amyloid-beta peptide (Abeta) is central to the pathogenesis of Alzheimer's
      disease, and the low-density lipoprotein receptor-related protein (LRP) has been
      shown to alter Abeta metabolism in vitro. Here, we show that overexpression of a
      functional LRP minireceptor in the brain of PDAPP mice results in age-dependent
      increase of soluble brain Abeta, with no changes in Abeta plaque burden.
      Importantly, soluble brain Abeta was found to be primarily in the form of
      monomers/dimers and to be highly correlated with deficits in spatial learning and
      memory. These results provide in vivo evidence that LRP may contribute to memory
      deficits typical of Alzheimer's disease by modulating the pool of small soluble
      forms of Abeta.

PMID- 14732700
TI  - Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid
      lineage cells and involved in regulation of cytoskeletal architecture.
AB  - Here, we identified and characterized a Ly49 family member, designated as Ly49Q.
      The Ly49q gene encodes a 273-aa protein with an immunoreceptor tyrosine-based
      inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that
      the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation
      dependent manner. In contrast to other known members of the Ly49 family, Ly49Q
      was found not to be expressed on NK1.1(+) cells, but instead was detectable on
      virtually all Gr-1(+) cells, such as myeloid precursors in bone marrow.
      Monocytes/macrophages also expressed low levels of Ly49Q, and the expression was
      enhanced by the treatment of cells with IFN-gamma. Treatment of activated
      macrophages with anti-Ly49Q mAb induced rapid formation of polarized actin
      structures, showing filopodia-like structure on one side and lamellipodial-like
      structure on the other side. A panel of proteins became tyrosine-phosphorylated
      in myeloid cells when treated with the mAb. Induction of the phosphorylation
      depends on the ITIM of Ly49Q. Thus, Ly49Q has unique features different from
      other known Ly49 family members and appears to be involved in regulation of
      cytoskeletal architecture of macrophages through ITIM-mediated signaling.

PMID- 14732701
TI  - Vertebrate ultraviolet visual pigments: protonation of the retinylidene Schiff
      base and a counterion switch during photoactivation.
AB  - For visual pigments, a covalent bond between the ligand (11-cis-retinal) and
      receptor (opsin) is crucial to spectral tuning and photoactivation. All
      photoreceptors have retinal bound via a Schiff base (SB) linkage, but only UV
      sensitive cone pigments have this moiety unprotonated in the dark. We
      investigated the dynamics of mouse UV (MUV) photoactivation, focusing on SB
      protonation and the functional role of a highly conserved acidic residue (E108)
      in the third transmembrane helix. On illumination, wild-type MUV undergoes a
      series of conformational changes, batho --> lumi --> meta I, finally forming the
      active intermediate meta II. During the dark reactions, the SB becomes protonated
      transiently. In contrast, the MUV-E108Q mutant formed significantly less batho
      that did not decay through a protonated lumi. Rather, a transition to meta I
      occurred above approximately 240 K, with a remarkable red shift (lambda(max)
      approximately 520 nm) accompanying SB protonation. The MUV-E108Q meta I --> meta
      II transition appeared normal but the MUV-E108Q meta II decay to opsin and free
      retinal was dramatically delayed, resulting in increased transducin activation.
      These results suggest that there are two proton donors during the activation of
      UV pigments, the primary counterion E108 necessary for protonation of the SB
      during lumi formation and a second one necessary for protonation of meta I.
      Inactivation of meta II in SWS1 cone pigments is regulated by the primary
      counterion. Computational studies suggest that UV pigments adopt a switch to a
      more distant counterion, E176, during the lumi to meta I transition. The findings
      with MUV are in close analogy to rhodopsin and provides further support for the
      importance of the counterion switch in the photoactivation of both rod and cone
      visual pigments.

PMID- 14732702
TI  - Molecular basis for the inhibition of G protein-coupled inward rectifier K(+)
      channels by protein kinase C.
AB  - G protein-coupled inward rectifier K(+) (GIRK) channels regulate cellular
      excitability and neurotransmission. The GIRK channels are activated by a number
      of inhibitory neurotransmitters through the G protein betagamma subunit
      (G(betagamma)) after activation of G protein-coupled receptors and inhibited by
      several excitatory neurotransmitters through activation of phospholipase C. If
      the inhibition is produced by PKC, there should be PKC phosphorylation sites in
      GIRK channel proteins. To identify the PKC phosphorylation sites, we performed
      systematic mutagenesis analysis on GIRK4 and GIRK1 subunits expressed in Xenopus
      oocytes. Our data showed that the heteromeric GIRK1/GIRK4 channels were inhibited
      by a PKC activator phorbol 12-myristate 13-acetate (PMA) through reduction of
      single channel open-state probability. Direct application of the catalytic
      subunit of PKC to excised patches had a similar inhibitory effect. This
      inhibition was greatly eliminated by mutation of Ser-185 in GIRK1 and Ser-191 in
      GIRK4 that remained G protein sensitive. The PKC-dependent phosphorylation seems
      to mediate the channel inhibition by the excitatory neurotransmitter substance P
      (SP) as specific PKC inhibitors and mutation of these PKC phosphorylation sites
      abolished the SP-induced inhibition of GIRK1/GIRK4 channels. Thus, these results
      indicate that the PKC-dependent phosphorylation underscores the inhibition of
      GIRK channels by SP, and Ser-185 in GIRK1 and Ser-191 in GIRK4 are the PKC
      phosphorylation sites.

PMID- 14732703
TI  - Retinoblastoma susceptibility gene product (pRb) and p107 functionally separate
      the requirements for serum and anchorage in the cell cycle G1-phase.
AB  - Growth factors and cell anchorage are both required for cell cycle G(1)-phase
      progression, but it is unclear whether their function is mediated through the
      same set of cell cycle components and whether they are both required during the
      same periods of time. We separately analyzed the requirements of serum and
      anchorage during G(1)-phase progression and found that human dermal fibroblasts
      as well as wild type, pRb(-/-), and p107(-/-) mouse embryonic fibroblasts needed
      serum (growth factors) until mid-G(1)-phase but required cell anchorage until
      late G(1)-phase to be competent for S-phase entry. Importantly, however, pRb/p107
      double-null mouse embryonic fibroblasts lacked serum requirement in mid-G(1)
      phase but still required cell anchorage until late G(1)-phase to enter S-phase.
      Our results indicate that pRb and p107 do not constitute the last control point
      for extracellular factors during G(1)-phase progression, and they functionally
      separate the requirements for serum and cell anchorage in terms of involved cell
      cycle components.

PMID- 14732704
TI  - Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls
      thymic emigration.
AB  - S1P(1) is a widely distributed G protein-coupled receptor whose ligand,
      sphingosine 1-phosphate, is present in high concentrations in the blood. The
      sphingosine 1-phosphate receptor-signaling pathway is believed to have potent
      effects on cell trafficking in the immune system. To determine the precise role
      of the S1P(1) receptor on T-cells, we established a T-cell-specific S1P(1) knock
      out mouse. The mutant mice showed a block in the egress of mature T-cells into
      the periphery. The expression of the S1P(1) receptor was up-regulated in mature
      thymocytes, and its deletion altered the chemotactic responses of thymocytes to
      sphingosine 1-phosphate. The results indicated that the expression of the S1P(1)
      receptor on T-cells controls their exit from the thymus and entry into the blood
      and, thus, has a central role in regulating the numbers of peripheral T-cells.

PMID- 14732705
TI  - Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL
      yields Pbeta, a nuclear-targeted peptide.
AB  - Regulated intramembrane proteolysis (RIP) is an emerging paradigm in signal
      transduction. RIP is mediated by intramembrane-cleaving proteases (I-CliPs),
      which liberate biologically active nuclear or secreted domains from their
      membrane-tethered precursor proteins. The yeast Pcp1p/Rbd1p protein is a Rhomboid
      like I-CliP that regulates mitochondrial membrane remodeling and fusion through
      cleavage of Mgm1p, a regulator of these essential activities. Although this
      ancient function is conserved in PARL (Presenilins-associated Rhomboid-like
      protein), the mammalian ortholog of Pcp1p/Rbd1p, the two proteins show a strong
      divergence at their N termini. However, the N terminus of PARL is significantly
      conserved among vertebrates, particularly among mammals, suggesting that this
      domain evolved a distinct but still unknown function. Here, we show that the
      cytosolic N-terminal domain of PARL is cleaved at positions 52-53 (alpha-site)
      and 77-78 (beta-site). Whereas alpha-cleavage is constitutive and removes the
      mitochondrial targeting sequence, beta-cleavage appears to be developmentally
      controlled and dependent on PARL I-CliP activity supplied in trans. The beta
      cleavage of PARL liberates Pbeta, a nuclear targeted peptide whose sequence is
      conserved only in mammals. Thus, in addition to its evolutionarily conserved
      function in regulating mitochondrial dynamics, PARL might mediate a mammalian
      specific, developmentally regulated mitochondria-to-nuclei signaling through
      regulated proteolysis of its N terminus and release of the Pbeta peptide.

PMID- 14732706
TI  - Amyloid precursor protein mediates proinflammatory activation of monocytic
      lineage cells.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder characterized by
      extracellular deposition of beta-amyloid (Abeta) peptide containing neuritic
      plaques. Abeta peptides are proteolytically derived from the membrane-bound
      amyloid precursor protein (APP). Although the function of APP is not entirely
      clear, previous studies demonstrate that neuronal APP colocalizes with beta(1)
      integrin receptors at sites of focal adhesion, suggesting that APP is involved in
      mediating neuronal process adhesion. Integrin-dependent adhesion is also a well
      characterized component of immune cell proinflammatory activation. Using primary
      mouse microglia and the human monocytic cell line, THP-1, we have begun
      investigating the role of APP in integrin-dependent activation. Co
      immunoprecipitation studies demonstrate that APP is recruited into a multi
      receptor signaling complex during beta(1) integrin-mediated adhesion of
      monocytes. Stimulation induces a subsequent, specific recruitment of tyrosine
      phosphorylated proteins to APP, including Lyn and Syk. Antibody cross-linking of
      cell surface APP leads to a similar response characterized by activation and
      recruitment of tyrosine kinases to APP as well as subsequent activation of
      mitogen-activated protein kinases and increased proinflammatory protein levels.
      These data demonstrate that APP can act as a proinflammatory receptor in
      monocytic lineage cells and provide insight into the contribution of this protein
      to the inflammatory conditions described in Alzheimer's disease.

PMID- 14732707
TI  - Similarity of binding sites of human matrix metalloproteinases.
AB  - Tissue components hydrolyzing matrix metalloproteinases (MMPs) exhibit a high
      sequence similarity (56-64% in catalytic domains) and yet a significant degree of
      functional specificity. The hexapeptide-binding sites of 24 known human MMPs were
      compared in terms of their force field interaction energies with five probes that
      are most frequently encountered in substrates and inhibitors. The probes moved
      along a grid enclosing partially flexible binding sites in rigid catalytic
      domains that were represented by published experimental structures and
      comparative models and new comparative models for nine most recently
      characterized MMPs. For individual MMPs, representative interaction energies were
      obtained as averages for all suitable experimental structures. Correlations of
      the representative energies for all MMP pairs were succinctly catalogued for
      individual probes, subsites, and correlation levels. Among the probes (neutral
      sp(3) carbon and sp(3) oxygen, positive sp(3) nitrogen and hydrogen, and negative
      carbonyl oxygen), the last probe is least distinctive. Similarities of subsites
      are decreasing as S1 ' > S2 > S3 ' > S1 approximately S3 > S2 '. Most
      interesting, occupancies of subsites in published structures of MMP-inhibitor
      complexes follow an almost parallel trend, alluding to overall low selectivity of
      known MMP inhibitors. Flexible subsite S1 ' that appears as the specificity
      pocket in rigid x-ray structures is actually very similar among individual MMPs.
      Several correlations indicated that MMPs 3, 8, and 12 have similar binding sites.
      Modeling results are corroborated with published experimental data on MMP
      inhibition and substrate specificities. The results provide numerous clues for
      development of specific inhibitors and substrates, as well as for selection of
      MMPs for testing that provides maximum information without redundant experiments.

PMID- 14732708
TI  - Appropriate NR1-NR1 disulfide-linked homodimer formation is requisite for
      efficient expression of functional, cell surface N-methyl-D-aspartate NR1/NR2
      receptors.
AB  - A c-Myc epitope-tagged N-methyl-D-aspartate receptor NR1-2a subunit was
      generated, NR1-2a(c-Myc), where the tag was inserted after amino acid 81. NR1
      2a(c-Myc) /NR2A receptors when expressed in mammalian cells are not trafficked to
      the cell surface nor do they yield cell cytotoxicity post-transfection. NR1-2a(c
      Myc) was, however, shown to assemble with NR2A subunits by immunoprecipitation
      and [(3)H]MK801 radioligand binding assays. Immunoblots of cells co-transfected
      with wild-type NR1-2a/NR2A subunits yielded two NR1-2a immunoreactive species
      with molecular masses of 115 and 226 kDa. Two-dimensional electrophoresis under
      non-reducing and reducing conditions revealed that the 226-kDa band contained
      disulfide-linked NR1-2a subunits. Only the 115-kDa NR1-2a species was detected
      for NR1-2a(c-Myc)/NR2A. The c-Myc epitope is inserted adjacent to cysteine 79 of
      the NR1-2a subunit; therefore, it is possible that the tag may prevent the
      formation of NR1 disulfide bridges. A series of cysteine --> alanine NR1-2a
      mutants was generated, and the NR1-2a mutants were co-expressed with NR2A or NR2B
      subunits in mammalian cells and characterized with respect to cell surface
      expression, cell cytotoxicity post-transfection, co-association by
      immunoprecipitation, and immunoblotting following SDS-PAGE under both reducing
      and non-reducing conditions. When co-expressed with NR2A in mammalian cells, NR1
      2a(C79A)/NR2A displayed similar properties to NR1-2a(c-Myc)/NR2A in that the 226
      kDa NR1 immunoreactive species was not detectable, and trafficking to the cell
      surface was impaired compared with wild-type NR1/NR2 receptors. These results
      provide the first biochemical evidence for the formation of NR1-NR1 intersubunit
      disulfide-linked homodimers involving cysteine 79. They suggest that disulfide
      bridging and structural integrity within the NR1 N-terminal domain is requisite
      for cell surface N-methyl-D-aspartate receptor expression.

PMID- 14732709
TI  - Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import
      Inhibitor.
AB  - Staphylococcal enterotoxin B and related toxins that target T cells have the
      capacity to elicit systemic inflammation, tissue injury, and death. Genes that
      encode mediators of inflammation can be globally inhibited by blocking the
      nuclear import of stress-responsive transcription factors. Here we show that cell
      permeant peptides targeting Rch1/importin alpha/karyopherin alpha 2, a nuclear
      import adaptor protein, are delivered to T cells where they inhibit the
      staphylococcal enterotoxin B-induced production of inflammatory cytokines ex vivo
      in cultured primary spleen cells and in vivo. The systemic production of tumor
      necrosis factor alpha, interferon gamma, and interleukin-6 was attenuated in mice
      either by a cell-permeant cyclized form of SN50 peptide or by a transgene whose
      product suppresses the nuclear import of transcription factor nuclear factor
      kappa B in T cells. The extent of liver apoptosis and hemorrhagic necrosis was
      also reduced, which correlated with significantly decreased mortality rates.
      These findings highlight nuclear import inhibitors as a potentially useful
      countermeasure for staphylococcal enterotoxin B and other toxins that trigger
      harmful systemic inflammatory responses.

PMID- 14732710
TI  - Kinetic evidence for channeling of dopamine between monoamine transporter and
      membranous dopamine-beta-monooxygenase in chromaffin granule ghosts.
AB  - The nature of coupling between the uptake and dopamine-beta-monooxygenase
      (DbetaM) catalyzed hydroxylation of dopamine (DA) was studied in bovine
      chromaffin granule ghosts. Initial rate and transient kinetics of DA uptake and
      conversion were determined under a variety of conditions. The uptake kinetics of
      DA, norepinephrine (NE), and epinephrine demonstrate that DA is a better
      substrate than NE and epinephrine under optimal uptake conditions. The transient
      kinetics of DA accumulation and NE production under both optimal uptake and
      uptake and conversion conditions were zero-order with no detectable lag or burst
      periods. The mathematical analyses of the data show that a normal sequential
      uptake followed by the conversion process could not explain the observed
      kinetics, under any condition. On the other hand, all experimental data are in
      agreement with a mechanism in which DA is efficiently channeled from the
      vesicular monoamine transporter to membranous DbetaM for hydroxylation, prior to
      the release into the bulk medium of the ghost interior. The slow accumulation of
      DA under optimal conversion conditions appears to be caused by the slow leakage
      of DA from the channeling pathway to the ghost interior. Because DbetaM activity
      in intact granules is equally distributed between soluble and membranous forms of
      DbetaM, if an efficient channeling mechanism is operative in vivo, soluble DbetaM
      may not have access to the substrate, making the catalytic activity of soluble
      DbetaM physiologically insignificant, which is consistent with the increasing
      experimental evidence that membranous DbetaM may be the physiologically
      functional form.

PMID- 14732711
TI  - On the evolutionary origin of cyclooxygenase (COX) isozymes: characterization of
      marine invertebrate COX genes points to independent duplication events in
      vertebrate and invertebrate lineages.
AB  - In vertebrates, COX-1 and COX-2, two cyclooxygenase isozymes with different
      physiological functions and gene regulation, catalyze identical reactions in
      prostaglandin synthesis. It is still not understood why there are multiple forms
      of COX enzyme in the same cell type and when the evolutionary duplication of the
      COX gene occurred. Here we report the structure of two genes encoding for COX
      isozymes in the coral Gersemia fruticosa, the first non-vertebrate organism from
      which a cyclooxygenase was characterized. Both genes are about 20 kb in size and
      consist of nine exons. Intron/exon boundaries are well conserved between coral
      and mammalian COX genes. mRNAs of the previously reported G. fruticosa COX-A
      (GenBank trade mark accession number AY004222) and the novel COX-B share 94%
      sequence identity in the coding regions and less than 30% in the 5'- and 3'
      untranslated region. Transcripts of both COX genes are detectable in coral cells,
      although the transcriptional level of COX-A is 2 orders of magnitude higher than
      COX-B. Expression of both coral genes in mammalian cells gave functional proteins
      with similar catalytic properties. By data base analyses we also detected and
      constructed different pairs of COX genes from the primitive chordates, Ciona
      savignyi and Ciona intestinalis. These two gene pairs encode proteins with 50%
      intra-species and only 70% cross-species sequence identity. Our results suggest
      that invertebrate COX gene pairs do not correspond to vertebrate COX-1 and COX-2
      and are consistent with duplication of the COX gene having occurred independently
      in corals, ascidians, and vertebrates. It is evident that due to the importance
      and complexity of its regulatory role, COX has multiple isoforms in all organisms
      known to express it, and the genes encoding for the isozymes may to be regulated
      differently.

PMID- 14732712
TI  - Identification and characterization of structural domains of human ERp57:
      association with calreticulin requires several domains.
AB  - The amino acid sequence of ERp57, which functions in the endoplasmic reticulum
      together with the lectins calreticulin and calnexin to achieve folding of newly
      synthesized glycoproteins, is highly similar to that of protein disulfide
      isomerase (PDI), but they have their own distinct roles in protein folding. We
      have characterized the domain structure of ERp57 by limited proteolysis and N
      terminal sequencing and have found it to be similar but not identical to that of
      PDI. ERp57 had three major protease-sensitive regions, the first of which was
      located between residues 120 and 150, the second between 201 and 215, and the
      third between 313 and 341, the data thus being consistent with a four-domain
      structure abb'a'. Recombinant expression in Escherichia coli was used to verify
      the domain boundaries. Each single domain and a b'a' double domain could be
      produced in the form of soluble, folded polypeptides, as verified by circular
      dichroism spectra and urea gradient gel electrophoresis. When the ability of
      ERp57 and its a and a' domains to fold denatured RNase A was studied by
      electrospray mass analyses, ERp57 markedly enhanced the folding rate at early
      time points, although less effectively than PDI, but was an ineffective catalyst
      of the overall process. The a and a' domains produced only minor, if any,
      increases in the folding rate at the early stages and no increase at the late
      stages. Interaction of the soluble ERp57 domains with the P domain of
      calreticulin was studied by chemical cross-linking in vitro. None of the single
      ERp57 domains nor the b'a' double domain could be cross-linked to the P domain,
      whereas cross-linking was obtained with a hybrid ERpabb'PDIa'c polypeptide but
      not with ERpabPDIb'a'c, indicating that multiple domains are involved in this
      protein-protein interaction and that the b' domain of ERp57 cannot be replaced by
      that of PDI.

PMID- 14732713
TI  - Identification of splicing variants of Rapostlin, a novel RND2 effector that
      interacts with neural Wiskott-Aldrich syndrome protein and induces neurite
      branching.
AB  - Rho family GTPases regulate neuronal morphology. Rnd subfamily is a new branch of
      Rho family GTPases. Of these GTPases, Rnd2 is specifically expressed in brain. We
      recently identified Rapostlin as a novel effector of Rnd2. Rapostlin induces
      neurite branching in response to Rnd2 in PC12 cells. During the cloning of
      Rapostlin, we have found two mainly expressed splicing variants of Rapostlin
      (renamed as RapostlinL), RapostlinM and RapostlinS, lacking 29 residues and 61
      residues within the unique insert region at the center, respectively, and three
      minor variants, RapostlinLd, RapostlinMd, and RapostlinSd, each with the
      identical five-amino acid deletion from RapostlinL, RapostlinM, and RapostlinS,
      respectively. RapostlinL is predominantly expressed in brain, whereas RapostlinS
      is expressed ubiquitously. In a dot-blot assay, all splicing variants bind to
      Rnd2 in a GTP-dependent manner. However, RapostlinM and RapostlinS induce less
      neurite branching when coexpressed with Rnd2 in PC12 cells, indicating that the
      insert region is important for the branching activity of RapostlinL. All splicing
      variants bind to N-WASP in vitro and in vivo through the SH3 domain at the
      carboxyl terminus, and the SH3 domain is essential for branching activity of
      RapostlinL. In immunoprecipitation experiments, Rnd2 reduces RapostlinL-N-WASP
      interaction, whereas it has little effect on the interaction of RapostlinM or
      RapostlinS with N-WASP. Therefore, we found that functionally different splicing
      variants of Rapostlin have different responses to Rnd2 in association with N
      WASP.

PMID- 14732714
TI  - The canonical methionine 392 of matrix metalloproteinase 2 (gelatinase A) is not
      required for catalytic efficiency or structural integrity: probing the role of
      the methionine-turn in the metzincin metalloprotease superfamily.
AB  - Matrix metalloproteinases (MMPs) are an important family of extracellular
      proteases that process a variety of biologically significant molecules. MMPs are
      members of the metzincin superfamily of >770 zinc endopeptidases, which includes
      astacins, serralysins, adamalysins, leishmanolysins, and snapalysins. Metzincins
      are characterized by an absolutely conserved methionine residue COOH-terminal to
      the third histidine in the consensus sequence HEXXHXXGXX(H/D), where the
      histidine residues chelate a catalytic zinc ion. The canonical methionine is part
      of a tight 1,4-beta-turn that loops the polypeptide chain beneath the catalytic
      zinc ion, forming a hydrophobic floor to the Zn(2+) ion binding site. The role of
      this methionine is uncertain, but its absolute conservation indicates an
      essential catalytic or structural function. To investigate this hypothesis, we
      replaced Met-392 that forms the Met-turn of human MMP-2 (gelatinase A) by site
      directed mutagenesis. The catalytic competence of leucine and serine mutants was
      assessed. (M392L)MMP-2 and (M392S)MMP-2 cleaved the physiological substrates
      gelatin, native type I collagen, and the chemokine monocyte chemoattractant
      protein-3 with similar efficiency to wild-type MMP-2. These mutants also cleaved
      two quenched fluorescent peptide substrates with a k(cat)/K(m) comparable to wild
      type MMP-2 and underwent 4-aminophenylmercuric acetate-induced autoactivation
      with similar kinetics. (M392L)MMP-2 and (M392S)MMP-2 were inhibited by tissue
      inhibitor of metalloproteinases (TIMP)-1, -2, and -4 and by the zinc chelators
      1,10-phenanthroline and a synthetic hydroxamate inhibitor, Batimastat, similar to
      the wild-type protein, indicating an unaltered active site topography. A tryptic
      susceptibility assay also suggested that (M392L)MMP-2 and (M392S)MMP-2 were
      correctly folded. These results challenge the dogma that this methionine residue
      and the Met-turn, which are absolutely conserved in all of the subfamilies of the
      metzincins, play an essential role in catalysis or active site structure.

PMID- 14732715
TI  - HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides
      via epsin N-terminal homology domains.
AB  - Huntingtin-interacting protein 1-related (HIP1r) is the only known mammalian
      relative of huntingtin-interacting protein 1 (HIP1), a protein that transforms
      fibroblasts via undefined mechanisms. Here we demonstrate that both HIP1r and
      HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. In
      contrast to other ENTH domain-containing proteins, lipid binding is preferential
      to the 3-phosphate-containing inositol lipids, phosphatidylinositol 3,4
      bisphosphate and phosphatidylinositol 3,5-bisphosphate. Furthermore, the HIP1r
      ENTH domain, like that of HIP1, is necessary for lipid binding, and expression of
      an ENTH domain-deletion mutant, HIP1r/deltaE, induces apoptosis. Consistent with
      the ability of HIP1r and HIP1 to affect cell survival, full-length HIP1 and HIP1r
      stabilize pools of growth factor receptors by prolonging their half-life
      following ligand-induced endocytosis. Although HIP1r and HIP1 display only a
      partially overlapping pattern of protein interactions, these data suggest that
      both proteins share a functional homology by binding 3-phosphorylated inositol
      lipids and stabilizing receptor tyrosine kinases in a fashion that may contribute
      to their ability to alter cell growth and survival.

PMID- 14732716
TI  - Drosophila Pkd2 is haploid-insufficient for mediating optimal smooth muscle
      contractility.
AB  - Humans heterozygous for PKD1 or PKD2 develop autosomal dominant polycystic kidney
      disease, a common genetic disorder characterized by renal cyst formation and
      extrarenal complications such as hypertension and vascular aneurysms. Cyst
      formation requires the somatic inactivation of the wild type allele. However, it
      is unknown whether this recessive mechanism applies to life-threatening vascular
      aneurysms, which could involve weakening of the endothelial lining or surrounding
      vascular smooth muscle cells (SMCs). Drosophila Pkd2 at 33E3 (Pkd2) encodes a
      PKD2 family of Ca(2+)-activated Ca(2+)-permeable cation channels. We show here
      that loss-of-function Pkd2 mutations severely reduced the contractility of the
      visceral SMCs, which was restored by expressing wild type Pkd2 cDNA via a muscle
      specific Gal4 driver. The effect of Pkd2 mutations alone on the skeletal muscle
      was minimal but was exacerbated by ryanodine-induced perturbation of
      intracellular Ca(2+) stores. Consistent with this, Pkd2 interacted strongly with
      a ryanodine receptor mutation, causing a synergistic reduction of larval body
      wall contraction rate that is normally regulated through Ca(2+) oscillation
      during excitation-contraction coupling in the skeletal muscle. These results
      suggest that PKD2 cooperates with the ryanodine receptor to promote optimal
      muscle contractility through intracellular Ca(2+) homeostasis. Further genetic
      analysis indicated that Pkd2 is strongly haploinsufficient for normal SMC
      contractility. Since Ca(2+) homeostasis is a conserved mechanism for optimal
      muscle performance, our results raise the possibility that inactivation of just
      one PKD2 copy is sufficient to compromise vascular SMC contractility and function
      in PKD2 heterozygous patients, thus explaining their increased susceptibility to
      hypertension and vascular aneurysms.

PMID- 14732717
TI  - Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively,
      regulate lymphocyte recirculation and heart rate.
AB  - Sphingosine 1-phosphate (S1P) influences heart rate, coronary artery caliber,
      endothelial integrity, and lymphocyte recirculation through five related high
      affinity G-protein-coupled receptors. Inhibition of lymphocyte recirculation by
      non-selective S1P receptor agonists produces clinical immunosuppression
      preventing transplant rejection but is associated with transient bradycardia.
      Understanding the contribution of individual receptors has been limited by the
      embryonic lethality of the S1P(1) knock-out and the unavailability of selective
      agonists or antagonists. A potent, S1P(1)-receptor selective agonist structurally
      unrelated to S1P was found to activate multiple signals triggered by S1P,
      including guanosine 5'-3-O-(thio)triphosphate binding, calcium flux, Akt and
      ERK1/2 phosphorylation, and stimulation of migration of S1P(1)- but not S1P(3)
      expressing cells in vitro. The agonist also alters lymphocyte trafficking in
      vivo. Use of selective agonism together with deletant mice lacking S1P(3)
      receptor reveals that agonism of S1P(1) receptor alone is sufficient to control
      lymphocyte recirculation. Moreover, S1P(1) receptor agonist plasma levels are
      causally associated with induction and maintenance of lymphopenia. S1P(3), and
      not S1P(1), is directly implicated in sinus bradycardia. The sustained
      bradycardia induced by S1P receptor non-selective immunosuppressive agonists in
      wild-type mice is abolished in S1P(3)-/- mice, whereas S1P(1)-selective agonist
      does not produce bradycardia. Separation of receptor subtype usage for control of
      lymphocyte recirculation and heart rate may allow the identification of selective
      immunosuppressive S1P(1) receptor agonists with an enhanced therapeutic window.
      S1P(1)-selective agonists will be of broad utility in understanding cell
      functions in vitro, and vascular physiology in vivo, and the success of the
      chemical approach for S1P(1) suggests that selective tools for the resolution of
      function across this broad lipid receptor family are now possible.

PMID- 14732718
TI  - Type IV collagen is transcriptionally regulated by Smad1 under advanced glycation
      end product (AGE) stimulation.
AB  - Prolonged exposure to hyperglycemia is now recognized as the most significant
      causal factor of diabetic complications. Excessive advanced glycation end
      products (AGEs) as a result of hyperglycemia in tissues or in the circulation may
      critically affect the progression of diabetic nephropathy. In diabetic
      nephropathy, glomerulosclerosis is a typical pathologic feature characterized by
      the increase of the extracellular matrix (ECM). We have reported previously that
      alpha1 type IV collagen (Col4) is one of the major components of ECM, which is up
      regulated by AGEs, and that the overexpression of Col4 is transcriptionally
      regulated by an unknown transcription factor binding to the promoter. Here we
      identified this protein as Smad1 by yeast one-hybrid screening. Using chromatin
      immunoprecipitation and reporter assay, we observed that Smad1 directly regulated
      transcription for Col4 through the binding of Smad1 to the promoter of Col4.
      Smad1 was significantly induced along with Col4 in AGE-treated mesangial cells.
      Moreover, suppression of Smad1 by antisense morpholino resulted in a decrease of
      AGE-induced Col4 overproduction. To elucidate the interaction between
      transforming growth factor-beta and Smad1, we investigated whether activin
      receptor-liked kinase1 (ALK1) was involved in this regulation. AGE stimulation
      significantly increased the expression of the ALK1 mRNA in mesangial cells. We
      also demonstrated that Smad1 and ALK1 were highly expressed in human diabetic
      nephropathy. These results suggest that the modulation of Smad1 expression is
      responsible for the initiation and progression of diabetic nephropathy and that
      blocking Smad1 signaling may be beneficial in preventing diabetic nephropathy and
      other various diabetic complications.

PMID- 14732719
TI  - Amelioration of radiation-induced fibrosis: inhibition of transforming growth
      factor-beta signaling by halofuginone.
AB  - Radiation-induced fibrosis is an untoward effect of high dose therapeutic and
      inadvertent exposure to ionizing radiation. Transforming growth factor-beta (TGF
      beta) has been proposed to be critical in tissue repair mechanisms resulting from
      radiation injury. Previously, we showed that interruption of TGF-beta signaling
      by deletion of Smad3 results in resistance to radiation-induced injury. In the
      current study, a small molecular weight molecule, halofuginone (100 nm), is
      demonstrated by reporter assays to inhibit the TGF-beta signaling pathway, by
      Northern blotting to elevate inhibitory Smad7 expression within 15 min, and by
      Western blotting to inhibit formation of phospho-Smad2 and phospho-Smad3 and to
      decrease cytosolic and membrane TGF-beta type II receptor (TbetaRII). Attenuation
      of TbetaRII levels was noted as early as 1 h and down-regulation persisted for 24
      h. Halofuginone blocked TGF-beta-induced delocalization of tight junction ZO-1, a
      marker of epidermal mesenchymal transition, in NMuMg mammary epithelial cells and
      suggest halofuginone may have in vivo anti-fibrogenesis characteristics. After
      documenting the in vitro cellular effects, halofuginone (intraperitoneum
      injection of 1, 2.5, or 5 microg/mouse/day) efficacy was assessed using ionizing
      radiation-induced (single dose, 35 or 45 Gy) hind leg contraction in C3H/Hen
      mice. Halofuginone treatment alone exerted no toxicity but significantly lessened
      radiation-induced fibrosis. The effectiveness of radiation treatment (2 gray/day
      for 5 days) of squamous cell carcinoma (SCC) tumors grown in C3H/Hen was not
      affected by halofuginone. The results detail the molecular effects of
      halofuginone on the TGF-beta signal pathway and show that halofuginone may lessen
      radiation-induced fibrosis in humans.

PMID- 14732720
TI  - Spider and bacterial sphingomyelinases D target cellular lysophosphatidic acid
      receptors by hydrolyzing lysophosphatidylcholine.
AB  - Bites by Loxosceles spiders can produce severe clinical symptoms, including
      dermonecrosis, thrombosis, vascular leakage, hemolysis, and persistent
      inflammation. The causative factor is a sphingomyelinase D (SMaseD) that cleaves
      sphingomyelin into choline and ceramide 1-phosphate. A similar enzyme, showing
      comparable bioactivity, is secreted by certain pathogenic corynebacteria and acts
      as a potent virulence factor. However, the molecular basis for SMaseD toxicity is
      not well understood, which hampers effective therapy. Here we show that the
      spider and bacterial SMases D hydrolyze albumin-bound lysophosphatidylcholine
      (LPC), but not sphingosylphosphorylcholine, with K(m) values ( approximately 20
      40 microm) well below the normal LPC levels in blood. Thus, toxic SMases D have
      intrinsic lysophospholipase D activity toward LPC. LPC hydrolysis yields the
      lipid mediator lysophosphatidic acid (LPA), a known inducer of platelet
      aggregation, endothelial hyperpermeability, and pro-inflammatory responses.
      Introduction of LPA(1) receptor cDNA into LPA receptor-negative cells renders non
      susceptible cells susceptible to SmaseD, but only in LPC-containing media.
      Degradation of circulating LPC to LPA with consequent activation of LPA receptors
      may have a previously unappreciated role in the pathophysiology of secreted
      SMases D.

PMID- 14732721
TI  - Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and
      therapy.
AB  - Hypertension resistant to 2 antihypertensive drugs is more common among obese
      patients than among lean patients. The case we describe and the observations we
      report suggest that refractoriness among obese hypertensives is frequently caused
      by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels.
      In other words, obese hypertensives may have sleep apnea, obese hypertensives
      without sleep apnea may have inappropriately elevated levels of plasma
      aldosterone, and a surprising number of obese patients with sleep apnea also have
      elevated levels of aldosterone. The mechanisms by which obesity and obstructive
      sleep apnea increase aldosterone levels and raise blood pressure are not
      understood, but sympathetic nervous system activation and production of
      nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can
      be detected with a careful history and various sleep studies. Inappropriately
      elevated aldosterone levels can be detected by measuring the ratio of plasma
      aldosterone concentration to plasma renin activity. Successful treatment of these
      resistant hypertensives often can be achieved by devices that provide positive
      pressure to the upper airway to correct obstructive sleep apnea and by
      incorporating an aldosterone antagonist in the therapeutic regimen.

PMID- 14732723
TI  - Low birth weight predicts higher blood pressure but not dermal capillary density
      in two populations.
AB  - The association between low birth weight and high blood pressure is well
      established, but underlying mechanisms remain undefined. Vascular rarefaction,
      which may elevate peripheral vascular resistance, has been observed in
      capillaries of young men at risk for hypertension and men who had low birth
      weight. We looked for evidence that capillary rarefaction explains the
      association of low birth weight with high blood pressure in two cohorts.
      Participants in study 1 included 107 healthy boys aged 6 to 16 years recruited at
      random from a single school. Study 2 included 61 members of a cohort recruited at
      birth and studied at age 24 years. Measurements included indices of current size,
      blood pressure by automated sphygmomanometer, and dermal capillary density by
      video capillaroscopy of dorsal index finger skin after 10 minutes of venous
      occlusion. Lower birth weight predicted higher systolic blood pressure in both
      studies: in study 1, 3.57 mm Hg/kg birth weight (after adjustment for current
      height, 95% confidence interval 0.38 to 6.75, P<0.05); in study 2, 122+/-12 mm Hg
      in low birth weight (<2 kg) versus 115+/-9 in controls (P<0.05). Dermal capillary
      density was not associated in either group with birth weight or systolic blood
      pressure. We have found no evidence in these 2 cohorts that reduced capillary
      density explains the associations between lower birth weight and higher blood
      pressure.

PMID- 14732722
TI  - Cyclooxygenases, the kidney, and hypertension.
AB  - Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use
      were developed to avoid side effects of conventional NSAIDs, including
      gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed
      in the kidney and is highly regulated in response to alterations in intravascular
      volume. COX-2 metabolites have been implicated in maintenance of renal blood
      flow, mediation of renin release, and regulation of sodium excretion. COX-2
      inhibition may transiently decrease urine sodium excretion in some subjects and
      induce mild to moderate elevation of blood pressure. Furthermore, in conditions
      of relative intravascular volume depletion and/or renal hypoperfusion,
      interference with COX-2 activity can have deleterious effects on maintenance of
      renal blood flow and glomerular filtration rate. In addition to physiological
      regulation of COX-2 expression in the kidney, increased renal cortical COX-2
      expression is seen in experimental models associated with altered renal
      hemodynamics and progressive renal injury (decreased renal mass, poorly
      controlled diabetes), and long-term treatment with selective COX-2 inhibitors
      ameliorates functional and structural renal damage in these conditions.

PMID- 14732725
TI  - Nitric oxide mediates benefits of angiotensin II type 2 receptor overexpression
      during post-infarct remodeling.
AB  - We hypothesized that nitric oxide (NO) mediates the benefits of cardiac
      angiotensin II type 2 (AT(2)-R) overexpression during postmyocardial infarction
      (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG)
      mice with AT(2)-R overexpression were studied by cardiac magnetic resonance
      imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior
      descending artery occlusion and reperfusion. Sixteen TG mice were treated from
      day 1 through 28 post-MI with the NO synthase inhibitor N(G)-nitro-l-arginine
      methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index
      (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI),
      wall thickness, percent thickening, and ejection fraction (EF) were measured.
      Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen
      was quantified in noninfarcted regions. At baseline, heart rate (HR), blood
      pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct
      size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were
      similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41+/-0.18
      microL/g versus 2.53+/-0.14 microL/g in WT; 2.17+/-0.14 microL/g in TG-Rx;
      P<0.008 for both). At day 28, EF was higher in TG (46.3%+/-2.9%) compared with WT
      and TG-Rx (32.7+/-2.3% and 33.7+/-2.3, respectively; P<0.003 for both). Wall
      thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and
      TG-Rx. Noninfarcted region interstitial collagen was similar between groups.
      Thus, the NO pathway may mediate much of the benefits of cardiac AT(2)-R
      overexpression during post-MI remodeling.

PMID- 14732726
TI  - Universal salt reduction.

PMID- 14732727
TI  - Steady-state and dynamic responses of renal sympathetic nerve activity to air-jet
      stress in sinoaortic denervated rats.
AB  - This study examined the role of arterial baroreceptors in mediating the
      relationship between changes in the mean level and the amplitude of slow
      oscillations of renal sympathetic nerve activity (RSNA) during environmental
      stress. In 7 sham-operated (control) and 7 chronically (2 weeks before study)
      sinoaortic baroreceptor denervated (SAD) conscious rats, arterial pressure (AP)
      and RSNA were simultaneously recorded during two 15-minute periods, before and
      during the application of a mild environmental stressor (jet of air). Air-jet
      stress induced a similar degree of sympathoexcitation in both groups of rats.
      During stress in control rats, AP and RSNA spectral power in the mid-frequency
      (MF) range (0.27 to 0.74 Hz) increased, mainly as a consequence of an
      amplification of strongly coherent oscillations of approximately 0.4 Hz
      frequency. In SAD rats, MF fluctuations of AP and RSNA were reduced but not
      abolished before stress, tended to increase during stress, and were linearly
      related under both experimental conditions. However, in the MF range, there was
      no well-defined oscillation at any specific frequency. At the peak coherence
      frequency ( approximately 0.4 Hz), the gain of the transfer function from RSNA to
      AP did not change during stress in control rats and was similar to that measured
      in SAD rats, indicating that it mainly reflected the properties of the
      feedforward effect of RSNA on AP (ie, vascular reactivity). In summary, the
      parallelism between stress-induced changes in the mean level of RSNA and the
      amplitude of slow RSNA oscillations requires the functional integrity of the
      baroreceptor reflex, which is consistent with the hypothesis that slow AP and
      RSNA rhythms are resonant oscillations within the baroreceptor reflex loop.

PMID- 14732730
TI  - Rho/Rho-kinase pathway in the brainstem contributes to hypertension caused by
      chronic nitric oxide synthase inhibition.
AB  - Central nervous system mechanisms are involved in hypertension caused by chronic
      inhibition of nitric oxide (NO) synthesis. Chronic inhibition of NO synthesis
      might also activate the Rho/Rho-kinase pathway in the vasculature. We recently
      demonstrated that activation of the Rho/Rho-kinase pathway in the nucleus tractus
      solitarii (NTS) contributes to hypertensive mechanisms in spontaneously
      hypertensive rats. The aim of the present study was to determine whether
      activation of this pathway also contributes to neurogenic hypertensive mechanisms
      caused by chronic NO synthesis inhibition. The NO synthase inhibitor N(omega)
      nitro-L-arginine methyl ester (L-NAME) was administered to Wistar-Kyoto rats in
      their drinking water (1 mg/mL) for 2 weeks. Bilateral microinjection of Y-27632,
      a specific Rho-kinase inhibitor, into the NTS elicited decreases in arterial
      pressure, heart rate, and renal sympathetic nerve activity in control rats and L
      NAME-treated rats. The magnitude of the decrease, however, was significantly
      greater in L-NAME-treated than in control rats. In another group of rats, the
      specific Rho-kinase inhibitor, Y-27632, was administered intracisternally for 2
      weeks with a mini-osmotic pump from the beginning of treatment with L-NAME. Y
      27632 co-treatment significantly attenuated the increase in arterial pressure.
      Furthermore, the expression level of membranous RhoA and phosphorylation of the
      target proteins of Rho-kinase, the ERM (ezrin, radixin, moesin) family members,
      was significantly greater in L-NAME-treated rats than in control rats. These
      results indicate that activation of the Rho/Rho-kinase pathway in the NTS
      contributes to neurogenic hypertension caused by chronic NO synthase inhibition.

PMID- 14732731
TI  - Aberrant D1 and D3 dopamine receptor transregulation in hypertension.
AB  - Dopamine plays a role in the regulation of blood pressure by inhibition of sodium
      transport in renal proximal tubules (RPTs) and relaxation of vascular smooth
      muscles. Because dopamine receptors can regulate and interact with each other, we
      studied the interaction of D(1) and D(3) receptors in immortalized RPT cells and
      mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats
      (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats,
      the D(1)-like agonist, fenoldopam, increased D(3) receptor protein in a time
      dependent and concentration-dependent manner (EC(50)=4.5x10(-9) M, t(1/2)=15.8
      hours). In SHRs, fenoldopam (10(-5) M) actually decreased the expression of D(3)
      receptors. D(1) and D(3) receptor co-immunoprecipitation was increased by
      fenoldopam (10(-7) M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam
      in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D(1)
      and D(3) receptor proteins). Both D(3) (PD128907, Emax=80%+/-6%, pED(50)=5+/-0.1)
      and D(1)-like receptor (fenoldopam, Emax=81%+/-8%, pED(50)=5+/-0.2, n=12)
      agonists relaxed mesenteric arterial rings. Co-stimulation of D(1) and D(3)
      receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D(1) and
      D(3) receptors interact differently in WKY and SHRs. Altered interactions between
      D(1) and D(3) receptors may play a role in the pathogenesis of genetic
      hypertension, including human hypertension, because these receptors also interact
      in human vascular smooth muscle cells.

PMID- 14732732
TI  - Arterial stiffness and kidney function.
AB  - The vascular hallmark of subjects with end-stage renal disease undergoing
      hemodialysis is increased aortic stiffness, a phenomenon independent of mean
      arterial blood pressure, wall stress, and standard cardiovascular risk factors
      such as plasma glucose, cholesterol, obesity, and smoking. These observations
      suggest that subtle links might associate arterial stiffness and kidney function
      in normotensive and hypertensive populations. Recently, aortic pulse wave
      velocity and creatinine clearance have been shown to be statistically associated
      in subjects with plasma creatinine < or =130 micromol/L, again independently of
      mean arterial blood pressure and classical cardiovascular risk factors. This
      association was even shown to predominate in subjects younger than age 55 years.
      In addition, acceleration of aortic pulse wave velocity with age was more
      important in these subjects than in untreated normotensive control individuals,
      and the phenomenon was consistently predicted by baseline plasma creatinine
      values. Among all antihypertensive drugs, angiotensin-converting enzyme
      inhibitors only were shown to exhibit a significant and independent effect on
      aortic stiffness. The use of these drugs was significantly associated with
      improvement of large aortic stiffness in subjects treated for hypertension. In
      conclusion, increased stiffness of central arteries is independently associated
      with reduced creatinine clearance in subjects with mild to severe renal
      insufficiency, indicating that kidney diseases may interact not only with small
      but also with large conduit arteries, independently of age, blood pressure level,
      and classical cardiovascular risk factors. Whether sodium, divalent ionic species
      (calcium, phosphates), and the renin-angiotensin-aldosterone system play a role
      in such alterations remains to be elucidated.

PMID- 14732733
TI  - Peroxisome proliferator-activated receptor gamma: implications for cardiovascular
      disease.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor belonging to the nuclear hormone receptor
      superfamily. PPARgamma is expressed by macrophages, endothelial cells, and
      vascular smooth muscle cells. It regulates gene expression of key proteins
      involved in lipid metabolism, vascular inflammation, and proliferation
      contributing to atherogenesis and postangioplasty restenosis. The discovery of
      synthetic ligands for PPARgamma has led to significant enhancement of our
      understanding of the mechanism of their ligand-dependent activation and
      subsequent biological effects, particularly with respect to the role of PPARgamma
      in vascular pathophysiology. The thiazolidinedione PPARgamma agonists not only
      improve insulin resistance in patients with type II diabetes but also exert a
      broad spectrum of antiatherogenic effects in vitro and in animal models of
      atherosclerosis. In this review, we summarize the important role of PPARgamma as
      a molecular target for thiazolidinediones and its implications for the control of
      vascular inflammation and proliferation for the cardiovascular system.

PMID- 14732734
TI  - Daily nighttime melatonin reduces blood pressure in male patients with essential
      hypertension.
AB  - Patients with essential hypertension have disturbed autonomic cardiovascular
      regulation and circadian pacemaker function. Recently, the biological clock was
      shown to be involved in autonomic cardiovascular regulation. Our objective was to
      determine whether enhancement of the functioning of the biological clock by
      repeated nighttime melatonin intake might reduce ambulatory blood pressure in
      patients with essential hypertension. We conducted a randomized, double-blind,
      placebo-controlled, crossover trial in 16 men with untreated essential
      hypertension to investigate the influence of acute (single) and repeated (daily
      for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour
      ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated
      melatonin intake reduced systolic and diastolic blood pressure during sleep by 6
      and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night
      amplitudes of the rhythms in systolic and diastolic blood pressures were
      increased by 15% and 25%, respectively. A single dose of melatonin had no effect
      on blood pressure. Repeated (but not acute) melatonin also improved sleep.
      Improvements in blood pressure and sleep were statistically unrelated. In
      patients with essential hypertension, repeated bedtime melatonin intake
      significantly reduced nocturnal blood pressure. Future studies in larger patient
      group should be performed to define the characteristics of the patients who would
      benefit most from melatonin intake. The present study suggests that support of
      circadian pacemaker function may provide a new strategy in the treatment of
      essential hypertension.

PMID- 14732735
TI  - Short telomeres are associated with increased carotid atherosclerosis in
      hypertensive subjects.
AB  - Recent studies have shown that individuals with shorter telomeres present a
      higher prevalence of arterial lesions and higher risk of cardiovascular disease
      mortality. As a group, patients with high blood pressure are at an increased risk
      for cardiovascular diseases. However, some hypertensive patients are more prone
      than others to atherosclerotic lesions. The main objective of this study was to
      examine the relationship between telomere length, as expressed in white blood
      cells, and carotid artery atherosclerotic plaques in hypertensive males. Data
      from 163 treated hypertensive men who were volunteers for a free medical
      examination were analyzed. Extracranial carotid plaques were assessed with B-mode
      ultrasound. Telomere length was measured from DNA samples extracted from white
      blood cells. The results of this study show that telomere length was shorter in
      hypertensive men with carotid artery plaques versus hypertensive men without
      plaques (8.17+/-0.07 kb versus 8.46+/-0.07 kb; P<0.01). Multivariate analysis
      showed that in addition to age, telomere length was a significant predictor of
      the presence of carotid artery plaques. The findings from this study suggest that
      in the presence of chronic hypertension, which is a major risk factor for
      atherosclerotic lesions, shorter telomere length in white blood cells is
      associated with an increased predilection to carotid artery atherosclerosis.

PMID- 14732736
TI  - Decrease in hypothalamic gamma adducin in rat models of hypertension.
AB  - We have previously shown that a decrease in hypothalamic gamma adducin (gamma
      adducin) is associated with hypertension in the spontaneously hypertensive rat
      (SHR). In view of many inherent issues with SHR, our objective in the present
      study was to provide proof of this concept with the use of 2 nongenetic rat
      models of hypertension. Subcutaneous angiotensin II (Ang II) infusion for 2 weeks
      (55 ng/kg per day) resulted in an increase in blood pressure (BP) of 18 mm Hg.
      This was associated with a 70% decrease in hypothalamic gamma-adducin.
      Concomitant administration of losartan attenuated the development of hypertension
      and a decrease in gamma-adducin. Deoxycorticosterone acetate salt-induced
      hypertension also caused a 70% decrease in hypothalamic gamma-adducin. Finally,
      neuronal cultures from neonatal rat brains were incubated with 100 nmol/L Ang II
      for 4 hours to mimic the in vivo Ang II infusion rat model. This chronic
      incubation with Ang II resulted in a 60% decrease in the neuronal gamma-adducin.
      Taken together, these observations strengthen our hypothesis that a decrease in
      hypothalamic gamma-adducin is linked to hypertension.

PMID- 14732737
TI  - Alterations in sympathetic ganglionic transmission in response to angiotensin II
      in (mRen2)27 transgenic rats.
AB  - Hypertension in (mRen2)27 transgenic rats is partly dependent on activation of
      the sympathetic nervous system, but the role of ganglionic transmission is
      unknown. We assessed indices of synaptic plasticity (post-tetanic short-term
      potentiation [PTP] and long-term potentiation [LTP]) and sympathetic ganglionic
      transmission without tetany in superior cervical ganglia (SCG) of Hannover
      Sprague-Dawley rats (HnSD) versus (mRen2)27 rats. There were no differences in
      decay time constants [PTP=9 minutes; LTP=120 to 150 minutes in both (mRen2)27 and
      HnSD]. However, angiotensin (Ang) II increased PTP and LTP in SCG isolated from
      (mRen2)27 rats to a greater extent than HnSD. Candesartan (an AT1 antagonist)
      blocked the potentiation in both groups. Without a preceding tetanic pulse, 16-nM
      Ang II induced similar significant increases in ganglionic transmission of
      approximately 14% in both strains. Assessment of Ang II receptors by 125I
      [Sar1Thr8]-Ang II binding showed that the AT1-receptor subtype predominates in
      the ganglia. The density of receptors in the SCG was comparable in (mRen2)27 and
      HnSD rats, whether measured in tissue from ganglia removed and frozen versus
      ganglia used in the transmission testing, suggesting that upregulation of
      receptors in vitro after removal of SCG did not occur. The divergence of effects
      of Ang II on LTP and PTP [greater in (mRen2)27 than HnSD] and nontetany
      ganglionic transmission (similar in both strains) may reflect different locations
      of receptors (pre- versus postsynaptic) or different signaling mechanisms
      involved in the two responses. We suggest that functional Ang II receptors in SCG
      mediate physiological actions of Ang II on ganglionic transmission and may play a
      pivotal role in hypertension.

PMID- 14732738
TI  - Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA
      expression.
AB  - In the coarctation hypertension model, we showed both dissociation of plasma
      renin activity from cardiovascular-induced effects and the reversal of
      hypertension-induced responses by losartan. In this study, we investigated the
      effects of hypertension on the expression of brain renin-angiotensin system
      components and the simultaneous functional responses and effects of long-term
      angiotensin II (AT) receptor blockade on these responses. Rats were given vehicle
      or losartan for 9 days and subjected to subdiaphragmatic aortic constriction or
      sham surgery after 4 days of treatment. On the fifth postsurgical day, pressure
      and heart rate were measured in the conscious state; the brain was perfused and
      removed afterward. Sequential slices of brainstem were hybridized with 35S
      oligodeoxynucleotide probes for angiotensinogen, AT1A, and AT1B receptors and
      processed for autoradiography and densitometry. In vehicle-treated rats,
      hypertension was accompanied by tachycardia and marked increments in
      angiotensinogen and AT1A mRNA expression in the cardiovascular system-controlling
      brainstem areas. In the nucleus tractus solitarii, AT1A density was correlated
      with both pressure and heart rate values (P<0.01), whereas angiotensinogen levels
      were correlated with pressure only (P<0.05). Losartan did not change the pressure
      of hypertensive rats (142+/-4 versus 146+/-2 mm Hg, losartan versus vehicle) and
      the hypertension-induced angiotensinogen mRNA expression but did block both
      tachycardic response and hypertension-induced AT1A mRNA expression. Hypertension
      and losartan did not change AT1B mRNA expression. The hypertension-induced
      positive feedback on angiotensinogen and AT1A mRNA expression supports the
      concept of a permissive role for brain angiotensin II in orchestrating
      circulatory responses during the development of hypertension. These data also
      explain the efficacy of long-term AT1 receptor blockade to reverse hypertension
      induced effects.

PMID- 14732741
TI  - Positional identification of hypertension susceptibility genes on chromosome 2.
AB  - Chromosome 2 has been consistently identified as a genomic region with genetic
      linkage evidence suggesting that one or more loci contributes to blood pressure
      and hypertension status. As with all complex disease traits, following-up linkage
      evidence to identify the underlying susceptibility gene(s) is an arduous yet
      biologically and clinically important task. Using combined positional candidate
      gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts
      in narrowing a large region of chromosome 2, demonstrating evidence for linkage
      in several populations, and identifying underlying candidate hypertension
      susceptibility gene(s). Initial informatics efforts identified the boundaries of
      the region and the known genes within it. A total of 82 polymorphic sites in 8
      genes were genotyped in a large hypothesis-generating sample consisting of 1640
      African Americans, 1339 whites, and 1616 Mexican Americans. After resampling
      based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was
      identified as a primary candidate gene for hypertension. Polymorphisms in SLC4A5
      were subsequently genotyped and analyzed for validation in two other
      subcomponents of the FBPP, each contributing African Americans (N=461; N=778) and
      whites (N=550; N=967). Again, single nucleotide polymorphisms within this gene
      were significantly associated with blood pressure levels and hypertension status.
      Although not identifying a single causal gene variant that is significantly
      associated with blood pressure levels and hypertension status across all samples,
      the results further implicate SLC4A5 as a candidate hypertension susceptibility
      gene. Moreover, the present study validates previous evidence for one or more
      genes on chromosome 2 that influence hypertension-related phenotypes in the
      population-at-large.

PMID- 14732742
TI  - Neuregulin-1 induces a negative inotropic effect in cardiac muscle: role of
      nitric oxide synthase.
AB  - BACKGROUND: Deficient cardiac neuregulin/ErbB signaling increases susceptibility
      to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1)
      on myocardial contractility. METHODS AND RESULTS: NRG-1 (alpha and beta isoforms)
      induced a negative inotropic effect in isolated rabbit papillary muscles and a
      rightward shift of the dose-response curve to isoproterenol. Both effects were
      attenuated by L-NMMA, which suggests a role for NO synthase. In cultured rat
      cardiomyocytes, NRG-1beta enhanced nitrite production and resulted in
      phosphorylation of endothelial NO synthase and the serine/threonine kinase Akt.
      CONCLUSIONS: NRG-1 has negative inotropic effects that are preserved during beta
      adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes.

PMID- 14732743
TI  - High prevalence of peripheral arterial disease in persons with renal
      insufficiency: results from the National Health and Nutrition Examination Survey
      1999-2000.
AB  - BACKGROUND: Although renal insufficiency is a recognized risk factor for coronary
      artery disease, little is known about the epidemiology of lower-extremity
      peripheral arterial disease (PAD) in persons with renal insufficiency. METHODS
      AND RESULTS: We examined the cross-sectional association of PAD, defined as an
      ankle-brachial index (ABI) <0.9, and renal insufficiency, defined as an estimated
      creatinine clearance (CRCL) <60 mL. min(-1). 1.73 m(-2), among 2229 eligible
      participants in the National Health and Nutrition Examination Survey (NHANES)
      1999 to 2000. An estimated 1.2+/-0.3 million persons >/=40 years old with CRCL
      <60 mL. min(-1). 1.73 m(-2) (24%) have PAD defined as an ABI <0.9 (versus 3.7% of
      persons with CRCL >/=60 mL. min(-1). 1.73 m(-2)). The association of ABI <0.9
      with renal insufficiency was independent of potential confounders such as age,
      diabetes, hypertension, coronary artery disease, stroke history, and
      hypercholesterolemia (OR 2.5, 95% CI 1.2 to 5.1, P=0.011, referent category ABI
      1.0 to 1.3). CONCLUSIONS: Clinicians should be aware of the remarkably high
      prevalence of PAD among patients with renal insufficiency. In the clinical
      setting, accurate identification of patients with renal insufficiency combined
      with routine ABI measurement in this group would greatly enhance efforts to
      detect subclinical PAD.

PMID- 14732744
TI  - Prospective analysis of mannose-binding lectin genotypes and coronary artery
      disease in American Indians: the Strong Heart Study.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is a circulating immune factor
      responsible for opsonization of pathogens and directly activating complement.
      Common variations in the MBL gene are responsible for an opsonic deficiency that
      affects 5% to 7% of whites and are associated with increased susceptibility to
      infections. After a preliminary report associating these variations with coronary
      artery disease (CAD), we determined MBL genotypes in 3 American Indian
      communities experiencing an increased mortality and morbidity from CAD. METHODS
      AND RESULTS: We examined DNA from 434 participants in a population-based cohort,
      the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1
      promoter polymorphism were determined. The frequency of a composite genotype that
      conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls
      without CAD. A conditional logistic regression model indicated a univariate OR
      for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After
      adjustment for demographic and CAD risk factors, including type 2 diabetes
      mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5
      to 7.0, P=0.004). CONCLUSIONS: Variant MBL genotypes coding for markedly
      diminished levels of MBL are predictive of CAD. After adjustment for multiple
      traditional risk factors for ischemic heart disease, this association remains
      significant. A high prevalence of variant MBL alleles and CAD in this population
      suggests that potentially important public health benefits may accrue from future
      interventions based on these genotypes.

PMID- 14732745
TI  - Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model
      of chronic hind limb ischemia: benefits of a novel nonviral vector, gelatin.
AB  - BACKGROUND: Earlier studies have shown that adrenomedullin (AM), a potent
      vasodilator peptide, has a variety of cardiovascular effects. However, whether AM
      has angiogenic potential remains unknown. This study investigated whether AM gene
      transfer induces therapeutic angiogenesis in chronic hind limb ischemia. METHODS
      AND RESULTS: Ischemia was induced in the hind limb of 21 Japanese White rabbits.
      Positively charged biodegradable gelatin was used to produce ionically linked DNA
      gelatin complexes that could delay DNA degradation. Human AM DNA (naked AM
      group), AM DNA-gelatin complex (AM-gelatin group), or gelatin alone (control
      group) was injected into the ischemic thigh muscles. Four weeks after gene
      transfer, significant improvements in collateral formation and hind limb
      perfusion were observed in the naked AM group and AM-gelatin group compared with
      the control group (calf blood pressure ratio: 0.60+/-0.02, 0.72+/-0.03, 0.42+/
      0.06, respectively). Interestingly, hind limb perfusion and capillary density of
      ischemic muscles were highest in the AM-gelatin group, which revealed the highest
      content of AM in the muscles among the three groups. As a result, necrosis of
      lower hind limb and thigh muscles was minimal in the AM-gelatin group.
      CONCLUSIONS: AM gene transfer induced therapeutic angiogenesis in a rabbit model
      of chronic hind limb ischemia. Furthermore, the use of biodegradable gelatin as a
      nonviral vector augmented AM expression and thereby enhanced the therapeutic
      effects of AM gene transfer. Thus, gelatin-mediated AM gene transfer may be a new
      therapeutic strategy for the treatment of peripheral vascular diseases.

PMID- 14732746
TI  - Endogenous estrogen deficiency reduces proliferation and enhances apoptosis
      related death in vascular smooth muscle cells: insights from the aromatase
      knockout mouse.
AB  - BACKGROUND: Altered proliferation and death of vascular smooth muscle cells
      (VSMCs) are important mechanisms in vascular growth and remodeling. This study
      examined the effect of endogenous estrogens on VSMC proliferation. METHODS AND
      RESULTS: An estrogen-deficient animal model, the aromatase-knockout (ArKO) mouse,
      was used. Primary cultures of VSMCs were established from aortas of 11-week-old
      male and female ArKO and wild-type (WT) mice. In ArKO cells, the absence of
      aromatase cytochrome P450 mRNA expression was demonstrated by reverse
      transcription-polymerase chain reaction; Western blotting showed normal
      expression of estrogen receptor protein. Proliferative responses to serum or
      platelet-derived growth factor-BB were lower in ArKO than WT cells; 17beta
      estradiol (E2, 10 nmol/L) enhanced the response to platelet-derived growth factor
      BB in ArKO cells but inhibited the response in WT cells. E2 inhibited activity of
      mitogen-activated protein kinase ERK1/2 in WT but not ArKO cells. Apoptosis
      related death caused by tumor necrosis factor-alpha was greater in ArKO than in
      WT cells; this effect in ArKO was attenuated by E2. Differences in VSMC
      proliferation between ArKO and WT occurred in both sexes. Morphological studies
      in aortas derived from male mice at 1 year of age demonstrated that medial smooth
      muscle area was approximately 10% less in ArKO than WT mice at this age.
      CONCLUSIONS: Deficiency of endogenous estrogens reduces proliferation and
      enhances apoptosis-related death in VSMCs; exogenous E2 corrects these
      abnormalities.

PMID- 14732747
TI  - Targeted gene delivery to vascular tissue in vivo by tropism-modified adeno
      associated virus vectors.
AB  - BACKGROUND: Gene therapy offers an unprecedented opportunity to treat diverse
      pathologies. Adeno-associated virus (AAV) is a promising gene delivery vector for
      cardiovascular disease. However, AAV transduces the liver after systemic
      administration, reducing its usefulness for therapies targeted at other sites.
      Because vascular endothelial cells (ECs) are in contact with the bloodstream and
      are heterogeneous between organs, they represent an ideal target for site
      specific delivery of biological agents. METHODS AND RESULTS: We isolated human
      venous EC-targeting peptides by phage display and genetically incorporated them
      into AAV capsids after amino acid 587. Peptide-modified AAVs transduced venous
      (but not arterial) ECs in vitro, whereas hepatocyte transduction was
      significantly lower than with native AAV. Intravenous infusion of engineered AAVs
      into mice produced reduced vector accumulation in liver measured 1 hour and 28
      days after injection and delayed blood clearance rates compared with native AAV.
      Peptide-modified AAVs produced enhanced uptake of virions in the vena cava with
      selective transgene expression. Retargeting was dose dependent, and coinfusion of
      either heparin or free competing peptides indicated that uptake was principally
      independent of native AAV tropism and mediated via the peptide. CONCLUSIONS: AAV
      tropism can be genetically engineered by use of phage display-derived peptides to
      generate vectors that are selective for the vasculature.

PMID- 14732748
TI  - Elevated troponin T levels and lesion characteristics in non-ST-elevation acute
      coronary syndromes.
AB  - BACKGROUND: Elevated troponin T levels in non-ST-elevation acute coronary
      syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore,
      it has been reported that troponin T could help improve the effectiveness of such
      new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular
      weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS
      indicate the presence of thrombus at culprit lesions, and this hypothesis was
      verified through the use of coronary angioscopy. METHODS AND RESULTS: We studied
      57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy.
      Before catheterization, we obtained blood samples to determine troponin
      positivity, and the patients were then classified as either troponin-positive or
      troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at
      the culprit lesions, we examined the presence of coronary thrombus, yellow
      plaque, and complex plaque. Moreover, we compared the preinterventional
      angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI
      flow) between the two groups. Twenty-two patients were troponin-positive and 35
      patients were troponin-negative. Univariate analyses indicated that the TIMI flow
      and the incidence of coronary thrombus detected with angioscopy correlate with
      the elevated troponin T levels. A multivariate logistic regression analysis
      showed the presence of coronary thrombus detected with angioscopy to be the only
      independent factor associated with elevated troponin T levels in patients with
      NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42; P=0.0046). CONCLUSIONS: Using
      angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be
      strongly associated with the presence of coronary thrombus.

PMID- 14732749
TI  - Outcomes in patients with diabetes mellitus undergoing percutaneous coronary
      intervention in the current era: a report from the Prevention of REStenosis with
      Tranilast and its Outcomes (PRESTO) trial.
AB  - BACKGROUND: Diabetes portends an adverse prognosis in patients undergoing
      percutaneous coronary intervention (PCI). Whether improvements in current
      clinical practice (stents, IIb/IIIa antagonists) have resulted in substantial
      improvement of these outcomes remains an issue. The aim of this study was to
      determine the influence of diabetes on 9-month outcomes of patients undergoing
      PCI in the current era. METHODS AND RESULTS: The 11 482 patients enrolled in the
      Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) Trial were
      stratified according to the presence (n=2694) or absence (n=8798) of diabetes.
      Diabetic patients were older; were more likely to be female; had a higher
      proportion of congestive failure, hypertension, prior CABG, and unstable angina;
      and had higher body mass index and lower ejection fraction than nondiabetic
      patients (P<0.01 for all comparisons). The degree of multivessel disease was
      similar between the two groups. American College of Cardiology/American Heart
      Association type C lesions were more common in diabetic patients (17% versus 15%,
      P<0.01). Angiographic and procedural success rates and in-hospital events were
      similar between the two groups. The primary end point of death, myocardial
      infarction, or target vessel revascularization (TVR) was analyzed as time-to
      first event within 9 months of the index PCI. After adjusting for certain
      baseline characteristics, diabetes was independently associated with death at 9
      months (relative risk [RR], 1.87; 95% CI, 1.31 to 2.68, P<0.01) and with an
      increased likelihood of TVR (RR, 1.27; 95% CI, 1.14 to 1.42, P<0.01), as well as
      the composite end point of death/myocardial infarction/TVR (RR, 1.26; 95% CI,
      1.13 to 1.40, P<0.01). CONCLUSIONS: Despite advances in interventional
      techniques, diabetes remains a significant independent predictor of adverse
      events in the intermediate term after PCI.

PMID- 14732750
TI  - Cytomegalovirus infection impairs the nitric oxide synthase pathway: role of
      asymmetric dimethylarginine in transplant arteriosclerosis.
AB  - BACKGROUND: We hypothesized that cytomegalovirus (CMV) may contribute to the
      vasculopathy observed in cardiac allograft recipients by impairing the
      endothelial nitric oxide synthase pathway. We focused on asymmetric
      dimethylarginine (ADMA, the endogenous inhibitor of nitric oxide synthase) as a
      potential mediator of the adverse vascular effect of CMV. METHODS AND RESULTS:
      Heart transplant recipients manifested elevated plasma ADMA levels compared with
      healthy control subjects. Transplant patients with CMV DNA-positive leukocytes
      had higher plasma ADMA concentrations and more extensive transplant arteriopathy
      (TA). Human microvascular endothelial cells infected with the CMV isolates
      elaborated more ADMA. The increase in ADMA was temporally associated with a
      reduction in the activity of dimethylarginine dimethylaminohydrolase (DDAH, the
      enzyme that metabolizes ADMA). Infected cultures showed high levels of oxidative
      stress with enhanced endothelial production of superoxide anion. CONCLUSIONS: CMV
      infection in human heart transplant recipients is associated with higher ADMA
      elevation and more severe TA. CMV infection in endothelial cells increases
      oxidative stress, impairs DDAH activity, and increases ADMA elaboration. CMV
      infection may contribute to endothelial dysfunction and TA by dysregulation of
      the endothelial nitric oxide synthase pathway.

PMID- 14732751
TI  - N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha)
      on calcium transients and contraction in adult rat cardiomyocytes.
AB  - BACKGROUND: The negative effect of tumor necrosis factor-alpha (TNF-alpha) on
      heart contraction, which is mediated by sphingosine, is a major component in
      heart failure. Because the cellular level of glutathione may limit sphingosine
      production via the inhibition of the Mg-dependent neutral sphingomyelinase (N
      SMase), we hypothesized that cardiac glutathione status might determine the
      negative contractile response to TNF-alpha. METHODS AND RESULTS: We examined the
      effects of TNF-alpha in isolated cardiomyocytes obtained from control rats or
      rats that were given the glutathione precursor N-acetylcysteine (NAC, 100 mg IP
      per animal). In cardiomyocytes obtained from control rats, 25 ng/mL TNF-alpha
      increased reactive oxygen species generation and N-SMase activity (500% and 34%
      over basal, respectively) and decreased the amplitude of [Ca(2+)](i) in response
      to electrical stimulation (22% below basal). NAC treatment increased cardiac
      glutathione content by 42%. In cardiomyocytes obtained from NAC-treated rats, 25
      ng/mL TNF-alpha had no effect on reactive oxygen species production or N-SMase
      activity but increased the amplitude of [Ca(2+)](i) transients and contraction in
      response to electrical stimulation by 40% to 50% over basal after 20 minutes.
      This was associated with a hastened relaxation (20% reduction in t(1/2) compared
      with basal) and an increased phosphorylation of both Ser(16)- and Thr(17)
      phospholamban residues (260% and 115% of maximal isoproterenol effect,
      respectively). CONCLUSIONS: It is concluded that cardiac glutathione status, by
      controlling N-SMase activation, determines the severity of the adverse effects of
      TNF-alpha on heart contraction. Glutathione supplementation may therefore provide
      therapeutic benefits for vulnerable hearts.

PMID- 14732752
TI  - Atrial extracellular matrix remodeling and the maintenance of atrial
      fibrillation.
AB  - BACKGROUND: Remodeling occurs in both ventricle and atrium in dilated
      cardiomyopathy and heart failure. However, the alteration of atrial extracellular
      matrix components during remodeling and its effect on the electrical remodeling
      and atrial arrhythmia have never been explored. METHODS AND RESULTS: Atrial
      tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy
      and end-stage heart failure who underwent heart transplantation were examined.
      Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF
      (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were
      used as controls (CNs). Western Blot analysis revealed a selective downregulation
      of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups
      compared with the NAF and CN groups and an upregulation of atrial
      metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by
      the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type
      I collagen volume fraction (CVF-I) increased significantly in the PmAF group
      followed by the PsAF and NAF groups compared with that in CN. LA CVF-I
      significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF
      group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the
      frequency of AF recurrence. CONCLUSIONS: Atrial extracellular matrix remodeling
      manifested by the selective downregulation of TIMP-2 along with upregulation of
      MMP-2 and CVF-I in the atrium is associated with the development of sustained
      atrial fibrillation in patients with cardiomyopathy and heart failure.

PMID- 14732753
TI  - Amiodarone therapy for drug-refractory fetal tachycardia.
AB  - BACKGROUND: Fetal tachycardia complicated by ventricular dysfunction and hydrops
      fetalis carries a significant risk of morbidity and mortality. Transplacental
      digoxin is effective therapy in a small percentage, but there is no consensus
      with regard to antiarrhythmic treatment if digoxin fails. This study evaluates
      the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory
      fetal tachycardia with heart failure. METHODS AND RESULTS: Fetuses with incessant
      tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2)
      for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not
      effective were treated transplacentally with a loading dose of oral amiodarone
      for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks.
      Digoxin therapy was continued throughout gestation. Newborns were studied by
      transesophageal pacing or ECG monitoring to determine the mechanism of
      tachycardia. Three fetuses were delivered urgently in tachycardia during
      amiodarone loading, and 3 required additional antiarrhythmic agents for sustained
      cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%)
      with reentrant supraventricular tachycardia, 2 of 2 with ventricular or
      junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone
      related adverse effects were transient in 5 infants and 8 mothers. Mean
      gestational age at delivery was 37 weeks, with 100% survival. CONCLUSIONS: Orally
      administered amiodarone is safe and effective treatment for drug-refractory fetal
      tachycardia, specifically reentrant supraventricular tachycardia, junctional
      ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or
      ventricular dysfunction.

PMID- 14732754
TI  - Acetylcysteine reduces plasma homocysteine concentration and improves pulse
      pressure and endothelial function in patients with end-stage renal failure.
AB  - BACKGROUND: Increased oxidative stress, elevated plasma homocysteine
      concentration, increased pulse pressure, and impaired endothelial function
      constitute risk factors for increased mortality in patients with end-stage renal
      failure. METHODS AND RESULTS: We investigated the metabolic and hemodynamic
      effects of intravenous administration of acetylcysteine, a thiol-containing
      antioxidant, during a hemodialysis session in a prospective, randomized, placebo
      controlled crossover study in 20 patients with end-stage renal failure. Under
      control conditions, a hemodialysis session reduced plasma homocysteine
      concentration to 58+/-22% predialysis (mean+/-SD), whereas in the presence of
      acetylcysteine, the plasma homocysteine concentration was significantly more
      reduced to 12+/-7% predialysis (P<0.01). The reduction of plasma homocysteine
      concentration was significantly correlated with a reduction of pulse pressure. A
      10% decrease in plasma homocysteine concentration was associated with a decrease
      of pulse pressure by 2.5 mm Hg. Analysis of the second derivative of
      photoplethysmogram waveform showed changes of arterial wave reflectance during
      hemodialysis in the presence of acetylcysteine, indicating improved endothelial
      function. CONCLUSIONS: Acetylcysteine-dependent increase of homocysteine removal
      during a hemodialysis session improves plasma homocysteine concentration, pulse
      pressure, and endothelial function in patients with end-stage renal failure.

PMID- 14732755
TI  - Effects of off-pump versus on-pump coronary surgery on reversible and
      irreversible myocardial injury: a randomized trial using cardiovascular magnetic
      resonance imaging and biochemical markers.
AB  - BACKGROUND: There is biochemical evidence that off-pump coronary artery bypass
      grafting (OPCABG) reduces myocardial injury compared with the use of
      cardiopulmonary bypass (ONCABG), but the functional significance of this is
      uncertain. We hypothesized that OPCABG surgery would result in reduced
      postoperative reversible (stunning) and irreversible myocardial injury, as
      assessed by cardiovascular MRI (CMRI). METHODS AND RESULTS: In a single-center
      randomized trial, 60 patients undergoing multivessel total arterial
      revascularization were randomly assigned: 30 to OPCABG and 30 to ONCABG. Patients
      underwent preoperative and early postoperative cine MRI for assessment of global
      left ventricular function, and contrast-enhanced CMRI for assessment of
      irreversible myocardial injury. Serial troponin I measurements were obtained
      perioperatively and correlated with the CMRI findings. The mean preoperative
      cardiac index was similar in the 2 surgical groups (2.9+/-0.7 ONCABG; 2.9+/-0.8
      OPCABG; P=0.9). After surgery, the cardiac index was significantly higher in the
      OPCABG group (2.7+/-0.6 ONCABG; 3.2+/-0.8 OPCABG; P=0.04). New irreversible
      myocardial injury was similar in incidence (36% ONCABG; 44% OPCABG; P=0.8) and
      magnitude (6.3+/-3.6 g ONCABG; 6.8+/-4.0 g OPCABG; P=0.9) across the 2 groups.
      The median area-under-the-curve (AUC) troponin I values were significantly larger
      in the ONCABG group (182 versus 135 microg/L; P=0.02). There was a moderate
      correlation between the troponin I AUC values and mean mass of new myocardial
      hyperenhancement (r(2)=0.4; P=0.008). CONCLUSIONS: OPCABG results in
      significantly better left ventricular function early after surgery but does not
      reduce the incidence or extent of irreversible myocardial injury.

PMID- 14732756
TI  - Five-year follow-up after intracoronary gamma radiation therapy for in-stent
      restenosis.
AB  - BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial is a double
      blinded randomized study evaluating the effects of intracoronary radiation
      therapy (IRT) in patients with in-stent restenosis (ISR). METHODS AND RESULTS:
      One hundred thirty patients with ISR (100 native coronary and 30 vein grafts)
      underwent percutaneous transluminal coronary angioplasty, laser ablation,
      rotational atherectomy, or additional stenting (36% of lesions). Patients were
      randomized to either 192-Iridium IRT or placebo, with a prescribed dose of 15 Gy
      to a 2-mm radial distance from the center of the source. Angiographic restenosis
      (27% versus 56%, P=0.002) and target vessel revascularization (26% versus 68%,
      P<0.001) were reduced at 6 months in patients treated with IRT. Between 6 and 60
      months, patients treated with IRT compared with placebo had more target lesion
      revascularization (IRT, 21.6% versus placebo, 4.7%; P=0.04) and target vessel
      revascularization (IRT, 21.5% versus placebo, 6.1%; P=0.03). At 5 years, the
      major adverse cardiac event rate was significantly reduced with IRT (46.2% versus
      69.2%, P=0.008). CONCLUSIONS: In the Washington Radiation for In-Stent Restenosis
      Trial, patients with ISR treated with IRT using 192-Iridium had a reduction in
      the need for repeat target lesion and vessel revascularization at 6 months and 5
      years.

PMID- 14732757
TI  - Polymorphism of the soluble epoxide hydrolase is associated with coronary artery
      calcification in African-American subjects: The Coronary Artery Risk Development
      in Young Adults (CARDIA) study.
AB  - BACKGROUND: Modulation of endogenous epoxide levels by soluble epoxide hydrolase
      (sEH) in the endothelium represents an important mechanism in the regulation of
      cardiovascular function. We examined the relationship between a common,
      functional polymorphism of the human sEH gene and coronary artery calcification
      (CAC) in young, largely asymptomatic African-American and non-Hispanic white
      subjects. METHODS AND RESULTS: Multiple logistic regression and Tobit regression
      models were used to assess the relationship between the sEH Arg287Gln
      polymorphism and presence and quantity of CAC. Models adjusting for race (except
      in race-specific analyses), age, sex, smoking, body mass index, systolic blood
      pressure, LDL cholesterol, and HDL cholesterol were estimated. Allele and
      genotype frequency distributions were not significantly different between the 2
      ethnic groups (P=0.22; P=0.17, respectively). The Arg287Gln polymorphism of the
      sEH gene was a significant predictor of CAC status in African-American
      participants, either alone or after adjusting for other risk factors. African
      American subjects with at least 1 copy of the Gln287 allele had a 2-fold greater
      risk of having CAC compared with those not carrying this allele (95% CI, 1.1 to
      2.9; P=0.02). There was no relationship between Arg287Gln polymorphism and the
      probability of having CAC in white participants (OR, 0.8; 95% CI, 0.5 to 1.3;
      P=0.49). Inferences from multivariable Tobit regression were similar to those
      obtained in the logistic regression models, indicating that the Arg287Gln
      polymorphism was a significant independent predictor of both presence and
      quantity of CAC in African-American but not white subjects. CONCLUSIONS: These
      data suggest an intriguing and possibly novel role for sEH in the pathogenesis of
      atherosclerosis, which deserves additional investigation.

PMID- 14732758
TI  - Effects of chlorpromazine on excitation-contraction coupling events in fast
      twitch skeletal muscle fibres of the rat.
AB  - 1. Single mechanically skinned fibres from the rat extensor digitorum longus
      muscle, which allow access to intracellular compartments, were used to examine
      the effects of 0.5-100 microM chlorpromazine hydrochloride (CPZ) on the major
      steps of the excitation-contraction (E-C) coupling to elucidate the involvement
      of skeletal muscle in the neuroleptic malignant syndrome (NMS). 2. At 1 microM,
      CPZ caused a 20-30% increase in the force response induced by t-system
      depolarisation and a marked increase in the rate of caffeine-induced SR Ca(2+)
      release. At [CPZ]> or =2.5 microM, there was an initial increase followed by a
      marked decrease of the t-system depolarisation-induced force responses, while the
      potentiating effect on the caffeine-induced SR Ca(2+) release remained. These
      effects were reversible. 3. CPZ had no effect on the maximum Ca(2+)-activated
      force, but caused reversible, concentration-dependent increases in the Ca(2+)
      sensitivity of the contractile apparatus at [CPZ] > or =10 microM, with a 50%
      predicted shift of 0.11 pCa (-log [Ca(2+)]) units at 82.3 microM CPZ. 4. CPZ did
      not alter the rate of SR-Ca(2+) loading at 1 and 10 microM, but reversibly
      reduced it by approximately 40% at 100 microM by reducing the SR Ca(2+) pump.
      Nevertheless, the SR Ca(2+) content was greater when fibres became unresponsive
      to t-system-induced depolarisation in the presence than in the absence of 100
      microM CPZ. 5. The results show that CPZ has concentration-dependent stimulatory
      and inhibitory effects on various steps of the E-C coupling, which can explain
      the involvement of skeletal muscle in NMS and reconcile previous divergent data
      on CPZ effects on muscle.

PMID- 14732759
TI  - Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at
      the GABA rho 1 receptor.
AB  - 1. The mechanisms of action of antagonists of the gamma-aminobutyric acid C
      (GABA(C)) receptor picrotoxin, quercetin and pregnanolone were studied. 2. Ionic
      currents (chloride), mediated through human homomeric GABA rho(1) receptors
      expressed in Xenopus oocytes, were recorded by two-electrode voltage clamp. 3.
      Dose-response (D-R) curves and kinetic measurements of GABA rho(1) currents were
      carried out in the presence or absence of antagonists. Use-dependent actions were
      also evaluated. 4. Picrotoxin, quercetin and pregnanolone exerted noncompetitive
      actions. 5. IC(50) values measured at the EC(50) for GABA (1 microM) were as
      follows: picrotoxin 0.6+/-0.1 microM (Hill coefficient n=1.0+/-0.2); quercetin
      4.4+/-0.4 microM (n=1.5+/-0.2); pregnanolone 2.1+/-0.5 microM (n=0.8+/-0.1). 6.
      These antagonists produced changes only in the slope of the linear current
      voltage relationships, which was indicative of voltage-independent effects. 7.
      The effect of picrotoxin on GABA rho(1) currents was use-dependent, strongly
      relied on agonist concentration and showed a slow onset and offset. The mechanism
      was compatible with an allosteric inhibition and receptor activation was a
      prerequisite for antagonism. 8. The effect of quercetin was use-independent,
      showed relatively fast onset and offset, and resulted in a slowed time course of
      the GABA-evoked currents. 9. The effect of pregnanolone was use-independent,
      presented fast onset and a very slow washout, and did not affect current
      activation. 10. All the antagonists accelerated the time course of deactivation
      of the GABA rho(1) currents.

PMID- 14732760
TI  - Use of lithium and the risk of injurious motor vehicle crash in elderly adults:
      case-control study nested within a cohort.

PMID- 14732761
TI  - Presidential address: the American Head and Neck Society legacy: clinical care,
      teaching, and research: staying the course during stormy times.

PMID- 14732762
TI  - The TNM staging of health care leadership: the Hayes Martin lecture.

PMID- 14732763
TI  - Molecular assay to detect metastatic head and neck squamous cell carcinoma.
AB  - BACKGROUND: The presence or absence of metastatic disease in cervical lymph nodes
      is the single most important determinant of therapy and prognosis for patients
      with head and neck squamous cell carcinoma (HNSCC). However, histologic
      examination fails to detect metastatic disease in a subset of neck dissection
      specimens. The accuracy of neck staging may be improved by the use of molecular
      techniques. Cytokeratins 5, 14, and 20 may be appropriate markers for HNSCC
      because they are expressed in HNSCC but not in lymphatic tissue. DESIGN: To test
      the sensitivity of detection of cytokeratin 5, 14, and 20 messenger RNA by
      quantitative reverse transcription polymerase chain reaction (RT-PCR), full
      length coding DNA sequences were cloned and transcribed. The expression of
      cytokeratin 5, 14, and 20 messenger RNA was quantified in 4 HNSCC cell lines and
      11 tumors. A cell culture lymph node model was created. RESULTS: As few as 32
      molecules of cytokeratin 14 could be detected using quantitative RT-PCR.
      Cytokeratins 5 and 14 were easily detected in all 4 HNSCC cell lines and almost
      all tumors. Cytokeratin 20 was not a useful marker, as expression was absent or
      significantly reduced in cell lines and tumors. In the lymph node model,
      cytokeratin 14 quantitative RT-PCR was able to detect 1 cancer cell in a
      background of 10 million lymphatic cells. CONCLUSIONS: Quantitative RT-PCR
      detection of cytokeratin 5 or 14 is a sensitive new molecular technique that may
      be used for detection of cervical micrometastases in head and neck cancer.

PMID- 14732764
TI  - Presurgical cytoreduction of oral cancer using intra-arterial cisplatin and
      limited concomitant radiation therapy (Neo-RADPLAT).
AB  - OBJECTIVE: To determine the effectiveness of a cytoreduction strategy for oral
      cancer using a novel trimodal therapy. METHODS: Prospective analysis of 25
      patients treated between October 1995 and June 2000 with a protocol named neo
      RADPLAT consisting of 4 weekly intra-arterial infusions of cisplatin (150 mg/m2)
      and intravenous infusions of sodium thiosulfate (9 g/m2), and concurrent
      radiation therapy (2 daily doses of 50 Gy) followed by tumor nidusectomy (a
      conventional surgery) at 8 weeks. Five patients had T2 lesions and 20 patients
      had T3 lesions; the clinical neck cancer stages were N0 in 12 patients, N1 in 9,
      and N2 in 4 (2 N2a, 1 N2b, and 1 Nc); and there were 17 tumors of the oral cavity
      (11 of the oral tongue, 5 of the retromolar trigone, and 1 of the floor of mouth)
      and 8 of the oropharynx (4 of the tonsillar fossa, 3 of the base of tongue, and 1
      of the soft palate). RESULTS: Twenty patients (80%) had a complete response to
      chemoradiation in the primary site and 11 (79%) had a complete response in the
      neck. Among the 19 patients who had a tumor nidusectomy after chemoradiation, 5
      had residual cancer and required a conventional resection. With regard to major
      toxicity, there were 6 cases of grade 3 and 1 case of grade 4 hematologic
      effects, 1 case of grade 3 neurologic effect, 1 case of grade 3 gastrointestinal
      effect, 1 case of grade 5 cardiac effect, as well as 16 cases of grade 3
      mucositis. With a median follow-up of 56 months (range, 28-84 months), the 5-year
      estimates for overall survival, disease-specific survival, and locoregional
      control were 54%, 64%, and 74%, respectively. Fourteen patients remain without
      disease, 6 have died of the disease, and 5 have died of other causes.
      CONCLUSIONS: Preoperative intra-arterial chemoradiation cytoreduction followed by
      limited surgery is effective for controlling oral cancer. This tissue-sparing and
      reduced-radiation strategy may also preserve oral function.

PMID- 14732765
TI  - Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage
      possible?
AB  - BACKGROUND: Salvage surgery is often the only curative option for recurrent
      cancer. In patients whose initial tumor is stage T3 or T4, the primary therapy
      often makes salvage even more difficult. We therefore analyzed the outcome in
      patients who were originally treated for T3 or T4 squamous cell carcinoma of the
      oral cavity, larynx, oropharynx, or hypopharynx and who then had a recurrence and
      chose to undergo further therapy for cure. PATIENTS AND METHODS: From 1980 to
      2000, a total of 940 patients were treated for stage T3 or T4 cancer. Forty-eight
      patients underwent salvage therapy for recurrence: 24 for primary site
      recurrence, 20 for regional recurrence, and 4 for locoregional recurrence.
      RESULTS: The mean time to recurrence was 14.0 months, and the mean survival time
      was 26.2 months. Among the 28 patients treated for primary site recurrence, the
      mean time to rerecurrence was 12.6 months, and the mean survival time was 27.3
      months. Only 5 of the 28 patients had prolonged survival. The stage of the
      recurrent disease did not influence outcome. Among the 20 patients treated for
      neck recurrence, the mean time to recurrence was 14.0 months, and the mean
      survival time was 25.0 months. Six of the 20 patients had prolonged survival, but
      none had a recurrence in a previously dissected and irradiated neck. CONCLUSIONS:
      These results show the limited potential for survival in patients who have a
      recurrence after treatment for advanced primary site head and neck cancer.
      Patients who have not undergone all modalities of therapy have the potential for
      salvage, but even then the chances are limited. Given the morbidity of salvage
      therapy, and the limited chance for cure, physicians must cautiously counsel
      patients who are contemplating treatment of recurrent cancer after therapy for
      advanced disease.

PMID- 14732767
TI  - Prognostic significance of presentation-to-diagnosis interval in patients with
      oropharyngeal carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic impact of presentation-to-diagnosis
      interval (PDI) and its association with other clinical factors in patients with
      oropharyngeal squamous cell carcinoma (OpSCC). DESIGN: Retrospective cohort
      study. SETTING: Otolaryngology clinic of an academic medical center. PATIENTS:
      Eighty-seven patients with OpSCC referred to the otolaryngology service at the
      Johns Hopkins Medical Institutions from March 1994 to August 2001 were included
      in the study. Selection criteria included confirmed pathological diagnosis of
      OpSCC, availability of referral record for PDI determination, and no past history
      of oropharyngeal cancer. MAIN OUTCOME MEASURES: The PDI is defined as the time
      between the patient's first presentation to a medical professional for tumor
      related symptoms and the time when the diagnosis of OpSCC was made. The
      prognostic impact of PDI and its association with other clinical factors were
      assessed using univariate and multivariate analyses. RESULTS: Forty percent of
      patients (35/87) had a PDI of 3 months or longer. Referred otalgia, active
      smoking status at the time of diagnosis, stage IV disease, and advanced T stage
      were associated with a poor prognosis. Prolonged PDI itself was not associated
      with a significant decrease in survival in univariate analysis (hazard ratio,
      1.27; P =.52). Furthermore, no significant correlation was found between PDI and
      N stage, T stage, young age at presentation (<45 years), or tobacco use.
      CONCLUSIONS: Difficulty in making the diagnosis of OpSCC is evident by the high
      proportion of patients with PDI of 3 months or longer. The PDI does not appear to
      have an impact on survival. Referred otalgia, widely recognized as a strong
      indicator of invasive head and neck cancer, portends a poor prognosis.

PMID- 14732766
TI  - Intraoperative molecular margin analysis in head and neck cancer.
AB  - BACKGROUND: Tumor-specific molecular alterations in surgical margins have been
      shown to predict risk of local recurrence. However, assays used for these
      analyses are time-consuming and therefore cannot be used in the intraoperative
      setting. OBJECTIVE: To detect and quantify tumor-specific methylated promoter
      sequences in surgical margins in a time frame suitable for intraoperative use.
      DESIGN: A novel quantitative methylation-specific polymerase chain reaction
      (QMSP) protocol. METHODS: A total of 13 patients with head and neck squamous cell
      carcinoma (HNSCC) were initially characterized for molecular alterations in their
      tumor at the time of biopsy. Six primary tumors were found to harbor promoter
      hypermethylation for p16 and O6-methylguanine-DNA-methyltransferase (MGMT) genes.
      Rapid QMSP was then used to identify promoter hypermethylation of these genes in
      the surgical margins. Results were compared with standard intraoperative
      histologic frozen section analysis and with conventional QMSP. RESULTS: Using our
      rapid QMSP assay, we found that 3 patients had methylation-positive margins.
      Tumor margins from 2 patients were methylated for p16 alone, and margins from 1
      patient were methylated for p16 and MGMT simultaneously. Molecular margin
      analysis was completed in less than 5 hours, a time frame appropriate for
      selected major HNSCC resections that require combined primary tumor resection,
      cervical lymphadenectomy, and complex reconstruction. This technique was
      comparable in sensitivity to conventional QMSP. CONCLUSION: Rapid molecular
      margin analysis using QMSP is feasible and may be performed intraoperatively in
      selected patients with HNSCC that requires extensive resection.

PMID- 14732768
TI  - Techniques for radiofrequency ablation of head and neck tumors.
AB  - OBJECTIVES: To describe the various techniques that have been developed for
      application of radiofrequency ablation in the palliative treatment of recurrent
      and advanced head and neck malignant tumors. DESIGN: Case series with a follow-up
      of 3 to 18 months. SETTING: Faculty practice, research protocol, tertiary care
      academic medical center. PATIENTS: Fifteen treatments were administered over a 3
      year period to 12 patients with advanced and/or recurrent tumors. Eleven tumors
      were squamous cell carcinomas of the oral cavity, oropharynx, and maxillary
      sinus, and 1 tumor was a medullary thyroid carcinoma. Three of the 12 patients
      were treated on 2 separate occasions. Patients were selected as a referred sample
      and sent specifically for treatment with radiofrequency ablation because they
      were not candidates for the standard curative options of radiation or surgery. No
      patient refused enrollment, nor were any patients withdrawn because of adverse
      events. INTERVENTION: Radiofrequency ablation is a method of localized
      hyperthermia resulting in tissue necrosis. Ninety to 150 W of energy is applied,
      achieving intratumoral temperatures of 60 to 110 degrees C for 5 to 15 minutes
      per ablation. Techniques have been developed to apply radiofrequency ablation
      under direct vision, endoscopically, percutaneously, and with ultrasound and
      computed tomographic guidance. RESULTS: The radiofrequency ablation probe was
      accurately placed and treatment administered on 15 occasions. No perioperative
      deaths occurred. One patient suffered a stroke. Subjective patient improvement
      was reported with regard to pain (n=9), appearance (n=3), and function (n=4).

PMID- 14732769
TI  - Factors associated with staged reconstruction and successful stoma closure in
      tracheal resection and end-to-end anastomosis.
AB  - BACKGROUND: By analyzing the rate of successful decannulation in patients who
      underwent tracheal resection and end-to-end anastomosis, we tried to find the
      factors affecting the surgical outcome of tracheal stenosis. We also tried to
      discover the factors affecting the need for staged reconstruction. DESIGN AND
      SETTING: Retrospective study in a tertiary care center. PATIENTS: From 1988 to
      2001, 117 tracheal resections and primary end-to-end anastomoses in 110 patients
      were carried out. The statistical analysis was done from the data of 81 patients
      in whom the stenosis was caused mainly by internal trauma such as long-term
      intubation or tracheostomy. MAIN OUTCOME MEASURES: The success of surgery was
      defined as successful stoma closure; staged reconstructions were defined as cases
      in which the stoma was left open intentionally during the end-to-end anastomosis.
      RESULTS: The stoma could be successfully closed primarily in 67 (83%) of the 81
      cases, and staged reconstructions were needed in 22 (26%) of the patients. Older
      patients (>60 years) and patients with a higher grade of stenosis showed a
      significantly lower success rate. Staged operations were more frequently needed
      in cases with total stenosis and with combined stenosis of the trachea and the
      subglottis. CONCLUSIONS: In patients older than 60 years or with severe stenosis,
      the rate of successful stoma closure was low. A staged operation should be
      considered in cases with severe stenosis or stenosis not confined to the trachea.

PMID- 14732770
TI  - The role of intraoperative rapid parathyroid hormone monitoring for predicting
      thyroidectomy-related hypocalcemia.
AB  - OBJECTIVE: To determine if the intraoperative rapid parathyroid hormone (PTH)
      assay can be used to accurately predict postoperative calcium levels following
      total or completion thyroidectomy. DESIGN: A prospective study. SETTING: Tertiary
      care referral center. PATIENTS: One hundred four patients following a total or
      completion thyroidectomy.Intervention Intraoperative rapid plasma PTH levels were
      determined for patients undergoing a total or completion thyroidectomy. MAIN
      OUTCOME MEASURES: Parathyroid hormone levels were recorded after the induction of
      anesthesia, before excision, and 5, 10, and 20 minutes after thyroidectomy.
      Postoperative calcium levels were monitored every 6 hours until hospital
      discharge. Intraoperative PTH levels were correlated with postoperative calcium
      levels and clinical symptoms of hypocalcemia. RESULTS: Twenty-two patients
      (21.2%) required short-term postoperative calcium supplementation, and 2 (1.9%)
      required long-term calcium replacement. There was a statistically significant
      difference between those patients requiring calcium replacement and those who did
      not require calcium supplementation, for postoperative total calcium level (7.2
      vs 8.1 mg/dL [1.8 vs 2.0 mmol/L]; P<.001) and ionized calcium level (3.76 vs 4.36
      mg/dL [0.94 vs 1.09 mmol/L]; P<.001). In addition, the PTH changes from baseline
      demonstrated statistically significant differences at 5, 10, and 20 minutes after
      the excision between the 2 groups (P<.005). In those patients requiring calcium
      supplementation, 14 (64%) of 22 demonstrated a change in PTH level at 20 minutes
      of greater than 75% from baseline, and in those patients who did not require
      postoperative calcium supplementation, 61 (74%) of 82 demonstrated a change in
      PTH level of less than 75% from baseline (P<.005). CONCLUSION: Intraoperative PTH
      monitoring may be a useful tool in identifying patients who will not require
      postoperative calcium supplementation following total or completion
      thyroidectomy.

PMID- 14732771
TI  - Short hairpin RNA system to inhibit human p16 in squamous cell carcinoma.
AB  - OBJECTIVE: To develop short hairpin RNA (shRNA) vectors and virions to trigger
      RNA interference against human p16. DESIGN AND INTERVENTIONS: A modular vector
      based shRNA system was used to construct multiple distinct shRNA vectors against
      the unique exon 1alphaof p16. Target sequences were designed using rigid criteria
      for length and GC content, along with basic local alignment search tool (BLAST)
      evaluation to ensure targeting specificity. Individual shRNA-p16 cassettes were
      then cotransfected with a p16 expression vector and evaluated by Western blot.
      Cassettes showing a high level of p16 repression were used to construct shRNA-p16
      expressing adenoviral and retroviral vectors and tested in a human head and neck
      squamous cell carcinoma line expressing endogenous and exogenous p16. RESULTS:
      Adenoviral and retroviral transfer of shRNA-p16 significantly reduced p16 protein
      levels, while control constructs left p16 expression unchanged. CONCLUSIONS:
      Although p16 is a common target of inactivation in head and neck cancer, its
      biological role remains ill defined. RNA interference is rapidly becoming the
      standard to target selected genes of interest for inactivation. We have
      successfully inhibited p16 expression using shRNA cassettes with strong activity
      against human p16 and integrated these constructs into adenoviral and retroviral
      vectors for transient and integrated expression in human cells. Application of
      this novel modular system to primary human cells will allow the biological
      consequences of p16 loss to be examined both in vitro and in vivo.

PMID- 14732772
TI  - The role of computed tomographic scans in the management of the N-positive neck
      in head and neck squamous cell carcinoma after chemoradiotherapy.
AB  - OBJECTIVE: To determine the sensitivity and specificity of computed tomographic
      (CT) scanning in predicting residual cervical metastatic disease (N-positive
      neck) in patients undergoing curative radiotherapy and chemoradiotherapy for
      squamous cell carcinoma (SCC) of the upper aerodigestive tract. DESIGN:
      Retrospective case series (1995-2002) of patients undergoing radiotherapy and
      chemoradiotherapy for advanced head and neck SCC. METHODS: Study entry criteria
      included N-positive neck disease, a complete response to treatment at the primary
      tumor site, posttreatment CT scan, posttreatment neck dissection, and correlation
      of posttreatment CT scan with pathologic neck specimen. We calculated the
      sensitivity and specificity of the CT scan to predict the presence of residual
      cervical metastatic disease after curative radiotherapy and chemoradiotherapy.
      RESULTS: Forty-three patients (including 10 with bilateral N-positive necks) met
      the study criteria for analysis. Twenty (38%) of the 53 neck dissection specimens
      were positive for residual cervical metastatic disease. The sensitivity of the CT
      scan was 85%, while the specificity was only 24%. The positive predictive value
      of the CT scan was 40%. CONCLUSIONS: While the role of the posttreatment neck
      dissection remains controversial, the surgeon must rely on clinical examination
      and imaging studies. Our practice has been to perform planned staged neck
      dissections on all N2/N3 necks as well as N1 necks with an incomplete response to
      treatment. Based on our results, it appears that the CT scan technique lacks
      adequate sensitivity and specificity to reliably predict the presence of residual
      metastatic disease.

PMID- 14732773
TI  - Alcohol dehydrogenase 3 genotype as a risk factor for upper aerodigestive tract
      cancers.
AB  - OBJECTIVE: To assess alcohol dehydrogenase 3 (ADH3) polymorphism at position
      Ile349Val as indicator of risk factor for upper aerodigestive tract (UADT) cancer
      to verify its association with UADT cancer in nonalcoholic or nonsmoking
      individuals. DESIGN: Cross-sectional study. SETTING: Primary care or referral
      center. PATIENTS: The study group consisted of 141 consecutive patients with
      newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx,
      hypopharynx, or larynx admitted for surgical treatment. The comparison group
      consisted of 94 inpatients without cancer from the A. C. Camargo or other Sao
      Paulo (Brazil) hospital and 40 healthy individuals. INTERVENTION: All
      participants were interviewed and data were collected using a structured
      questionnaire. After written informed consent was obtained, 20 mL of blood was
      collected in heparinized tubes. MAIN OUTCOME MEASURES: Odds ratio for ADH3
      genotypes using logistic regression models. RESULTS: After adjustment for sex,
      age, tobacco use, and history of cancer in first-degree family relatives, a
      significantly higher odds ratio for UADT cancer was observed among individuals
      with AA genotype and low cumulative alcohol consumption (< or =100 kg of ethanol)
      (odds ratio = 3.8 [95% confidence interval, 1.5-9.7]). A 4-fold increase in odds
      ratio for UADT cancer among individuals with AA genotype and low tobacco
      consumption (< or =25 pack-years) was also found in the adjusted model.
      CONCLUSIONS: These results suggest that genotype AA may be a risk factor for UADT
      cancer, especially in individuals with low alcohol or tobacco consumption.
      However, further epidemiological case-control or cohort studies, preferably
      prospective, are needed to establish the exact role of ADH3 polymorphism and its
      association with the development of UADT cancers.

PMID- 14732774
TI  - Prognoses of oral basaloid squamous cell carcinoma and squamous cell carcinoma: a
      comparison.
AB  - OBJECTIVE: To compare clinical and prognostic features in patients with basaloid
      squamous cell carcinoma (BSCC), poorly differentiated squamous cell carcinoma
      (PDSCC), and well to moderately differentiated squamous cell carcinoma (W/MSCC)
      of the oral cavity. DESIGN: Retrospective cohort. SETTING: Referral tertiary
      center. PATIENTS: Seventeen patients with primary oral BSCC, 27 with PDSCC, and
      27 with SCC. INTERVENTION: The 71 patients all had surgery and 52 had
      postoperative radiotherapy. MAIN OUTCOME MEASURES: Recurrences and survival.
      RESULTS: The median follow-up time was 52.4 months for patients with BSCC, 22.2
      months for those with PDSCC, and 13.8 months for those with SCC. No statistically
      significant differences on survival were found among the BSCC, PDSCC, and SCC
      groups. The 5-year cancer-specific survival rates were 50% for patients with
      BSCC, 37% for those with PSCC, and 49% for those with W/MSCC (P =.71); the 5-year
      overall survival rates were 46% for patients with BSSC, 18% for those with PSCC,
      and 41% for those with W/MSCC (P =.25). Disease-free survival was not
      significantly different among the BSCC, PSCC, and W/MSCC groups (P =.57). The 5
      year rate of disease-free survival was 40% for patients with BSCC, 37% for those
      with PSCC, and 53% for those with W/MSCC. CONCLUSIONS: The clinical course of
      BSCC is similar to the courses of PSCC and W/MSCC when clinical T and N
      classifications are matched. Prognosis does not differ for patients with BSCC of
      the oral cavity and those with conventional oral squamous cell carcinomas PSCC
      and W/MSCC.

PMID- 14732775
TI  - Sestamibi scans and intraoperative parathyroid hormone measurement in the
      treatment of primary hyperparathyroidism.
AB  - OBJECTIVE: To assess the value of preoperative sestamibi scanning and
      intraoperative parathyroid hormone (IOPTH) measurement in the treatment of
      patients with primary hyperparathyroidism due to multiple gland disease (MGD).
      DESIGN: Retrospective medical record review. SETTING: Tertiary care academic
      medical center. PATIENTS: The study population comprised 383 consecutive patients
      who underwent surgery for primary hyperparathyroidism at Long Island Jewish
      Medical Center, New Hyde Park, NY, between June 1, 1999, and January 31, 2002.
      INTERVENTIONS: Sestamibi scanning, IOPTH measurement, bilateral parathyroid
      exploration, and minimally invasive parathyroid surgery. MAIN OUTCOME MEASURES:
      Rate of postoperative persistent hyperparathyroidism. RESULTS: A total of 376
      patients met the requirements for inclusion in the study. There were 275 women
      (73%) and 101 men (27%). Of the patients, 325 (86%) had single adenomas, 28 (7%)
      had double adenomas, 16 (4%) had 3 or more abnormal glands, and 1 had parathyroid
      cancer. There were 9 cases (2%) of persistent or recurrent hypercalcemia after
      surgery. Duration of follow-up ranged from 1 to 37 (median, 7) months. The
      sensitivity of sestamibi scanning for detecting MGD was 23%, and the positive
      predictive value was 63%. Using the requirement that the IOPTH level fall by 50%
      from the first baseline and into the normal range, MGD was distinguished from
      solitary adenoma in 36 (88%) of 41 cases. CONCLUSIONS: The combination of
      preoperative sestamibi scanning and IOPTH measurement is effective in identifying
      cases of MGD and allows successful minimally invasive parathyroidectomy in most
      patients.

PMID- 14732776
TI  - Regression of HPV-positive tumors treated with a new Listeria monocytogenes
      vaccine.
AB  - BACKGROUND: Human papillomavirus (HPV) has been implicated in the pathogenesis of
      15% to 23% of head and neck squamous cell carcinomas as well as most
      oropharyngeal carcinomas. The viral oncoproteins E6 and E7 are expressed in HPV
      positive tumor cells and therefore provide ideal targets for tumor immunotherapy.
      Because of its unique ability to induce a cellular immune response, the
      intracellular bacteria Listeria monocytogenes has been studied as a potential HPV
      positive tumor vaccine. OBJECTIVE: To present a new recombinant strain of L
      monocytogenes that is effective in treating HPV-positive tumors in a murine
      model. DESIGN: A new recombinant L monocytogenes vaccine, Lm-ActA-E7, was
      designed by transforming an attenuated Listeria strain with an E7 expression
      cassette. The cassette consists of the HPV-16 E7 sequence fused to the Listeria
      protein ActA. The resultant strain of bacteria secretes E7 antigen as a fusion
      protein with ActA. METHODS: Tumors were established in C57BL/6 mice with a
      syngeneic HPV-positive cell line prior to treatment with vaccine. INTERVENTION:
      The Lm-ActA-E7 vaccine was administered intraperitoneally to the mice 5 days
      after tumors were established. A booster dose was administered 7 days after the
      first dose. Tumor progression was measured in 2 dimensions periodically after the
      vaccination. RESULTS: In C57BL/6 mice, the administration of Lm-ActA-E7 caused
      the complete regression of HPV-positive tumors in 6 of 8 mice tested. A cytotoxic
      T-lymphocyte assay revealed that administration of the vaccine caused the
      generation of cytotoxic T cells specific for E7. CONCLUSION: Our results
      demonstrate the ability of a new Listeria-based vaccine to generate a specific
      antitumor T-cell response and cause the regression of HPV-positive tumors in a
      murine model.

PMID- 14732777
TI  - Identification of patients with head and neck cancer using serum protein
      profiles.
AB  - BACKGROUND: New and more consistent biomarkers of head and neck squamous cell
      carcinoma (HNSCC) are needed to improve early detection of disease and to monitor
      successful patient management. OBJECTIVE: To determine if a new proteomic
      technology can correctly identify protein expression profiles for cancer in
      patient serum samples as well as detect the presence of a known tumor marker.
      DESIGN: Direct proteomic analysis and comparison. METHODS: The surface-enhanced
      laser desorption/ionization time of flight mass spectrometry (SELDI-TOF)
      ProteinChip system was used to screen for differentially expressed proteins in
      serum samples from 99 patients with HNSCC, 25 "healthy" smokers, and 102 healthy
      (normal) controls. Protein peak clustering and classification analyses of the
      SELDI spectral data were performed. RESULTS: Several proteins, with masses
      ranging from 2778 to 20,800 Da, were differentially expressed between patients
      with HNSCC and the normal controls. The serum protein expression profiles were
      used to develop a classification tree algorithm, which achieved a sensitivity of
      83.3% and a specificity of 90% in discriminating HNSCC from normal and healthy
      smoker controls. The positive and negative predictive values were 80% and 92%,
      respectively. A peak with an average mass of 10,068 Da was detected in sera from
      HNSCC patients and identified as the known biomarker metallopanstimulin-1 (MPS
      1), based on mass. Peak relative intensity of the 10,068-Da protein correlated
      consistently with MPS-1 levels detected by radioimmunoassay in serum samples of
      HNSCC patients and controls. The 10,068-Da peak was provisionally identified as
      MPS-1 by SELDI immunoassay. CONCLUSION: We propose that this technique may allow
      for the development of a reliable screening test for the early detection and
      diagnosis of HNSCC, as well as the potential identification of tumor biomarkers.

PMID- 14732779
TI  - Incidence of metastatic well-differentiated thyroid cancer in cervical lymph
      nodes.
AB  - OBJECTIVE: To determine the incidence of clinically positive lateral cervical
      nodes at presentation and after initial treatment in patients with well
      differentiated thyroid cancer. DESIGN: Retrospective chart review. SETTING:
      University-affiliated teaching hospitals. PATIENTS: A total of 508 patients who
      underwent a thyroidectomy as part of their initial treatment for well
      differentiated thyroid carcinoma between January 1978 and December 1999. Neck
      dissections were performed only for clinically palpable cervical nodes. MAIN
      OUTCOME MEASURES: Recurrence in the neck and survival. RESULTS: Forty-four
      patients (9%) had palpable lateral cervical lymph nodes at the time of surgery.
      All 31 patients younger than 45 years presenting with palpable positive nodes are
      alive and free of disease; 4 of 13 patients 45 years or older have died of
      thyroid cancer. Only 16 (3%) of 464 patients who did not undergo initial neck
      dissection had recurrence in lateral cervical nodes. Recurrence is more likely
      when the initial tumor is larger than 4 cm. In 216 patients younger than 45
      years, there were 5 (2%) recurrences in lateral cervical nodes; these patients
      remain alive and free of disease. In 248 patients 45 years or older, there were
      11 (4%) with recurrent disease in the lateral neck; 4 of these patients have died
      of thyroid cancer. CONCLUSIONS: An aggressive approach to detecting and treating
      occult lateral cervical nodes by techniques such as jugular node sampling,
      sentinel node biopsy, or image-guided needle biopsy is not necessary in most
      patients. Attempts to detect and remove occult lateral cervical lymph node
      metastases might be considered in older patients with large primary tumors.

PMID- 14732778
TI  - Positron emission tomography in the early follow-up of advanced head and neck
      cancer.
AB  - OBJECTIVE: To assess the clinical effect of an early follow-up positron emission
      tomography (PET) examination at the time of the first routine clinical control in
      patients with advanced-stage head and neck squamous cell carcinoma (HNSCC).
      DESIGN: Prospective, nonrandomized, case-control study. SETTING: Single referral
      center. PATIENTS AND INTERVENTION: A total of 26 patients (mean age, 56 years)
      with histologically confirmed stage III-IV HNSCC underwent PET before and
      approximately 6 weeks after the end of a combined treatment with radiation and
      chemotherapy with curative intent. The PET findings were confirmed by histologic
      analysis and a 6-month clinical follow-up. MAIN OUTCOME MEASURES: The presence of
      distant metastases, secondary synchronous cancers, and residual locoregional
      tissue was confirmed, and the effect on further clinical management was assessed.
      RESULTS: Using PET, we correctly identified residual tumor tissue, distant
      metastases, or a second primary tumor in 10 patients, 5 of whom had no clinical
      evidence of such findings. Results were true negative in 14 cases; false positive
      in 1; and false negative in 1. Sensitivity and specificity for follow-up PET
      scans were 90.9% and 93.3%, respectively. All patients with positive findings
      were evaluated for further treatment such as salvage surgery. CONCLUSIONS: Whole
      body PET scanning approximately 6 weeks after completion of a combined treatment
      regimen with radiation and chemotherapy can reliably identify locoregional
      residual cancer and distant metastases or secondary tumors in patients with
      advanced-stage HNSCC and has a direct influence on management decisions.

PMID- 14732780
TI  - Pathology quiz case. Sclerosing sarcoidosis of the larynx.

PMID- 14732781
TI  - Radiology quiz case. Ectopic thyroid tissue.

PMID- 14732783
TI  - New therapeutic approaches in pulmonary embolism.
AB  - Pulmonary embolism as a part of venous thromboembolic disease has a broad
      spectrum of clinical presentations from minimal disease to life-threatening right
      heart failure. Therapy has to be guided by the risk associated with the
      individual clinical state of the patient. As long as hemodynamics are entirely
      stable, anticoagulation is given in order to prevent early or late recurrence,
      thereby allowing for endogeneous thrombolysis and recovery. In hemodynamically
      instable patients, i.e. patients under cardiopulmonary resuscitation or in shock,
      there is the need for a rapid reduction of thrombus mass in order to restore
      right ventricular function. Systemic thrombolysis is the most feasible modality
      to reduce the thrombus burden of the pulmonary circulation in the short term. For
      hemodynamically stable patients with right ventricular dysfunction as assessed by
      echocardiography, there is still some controversy as to whether thrombolysis
      improves the long-term outcome. At the least, thrombolysis may positively modify
      the short-term course of acute disease in patients with an extremely low risk of
      bleeding. When the acute phase has been overcome, secondary prophylaxis with
      vitamin K antagonists has to be given. The duration of secondary prophylaxis
      requires an individual assessment of both the risk of recurrence and the risk of
      bleeding. In the near future, new anticoagulant drugs such as direct thrombin and
      factor Xa inhibitors will offer new treatment modalities for the acute phase as
      well as for secondary prophylaxis.

PMID- 14732784
TI  - Schistosomal cor pulmonale: A fluke in the Fas lane?

PMID- 14732785
TI  - Transbronchial needle aspiration and mediastinal staging in lung cancer.

PMID- 14732786
TI  - Serum soluble Fas in patients with Schistosomal cor pulmonale.
AB  - BACKGROUND: Schistosomal cor pulmonale is considered an important pathological
      condition in endemic areas. Few recent studies have reported the role of
      apoptosis in pulmonary hypertension. OBJECTIVES: The aim of this study was to
      assess serum levels of soluble Fas (sFas), an inhibitor of apoptosis, in patients
      with schistosomal cor pulmonale as compared to patients with cor pulmonale due to
      chronic obstructive pulmonary disease (COPD) and normal subjects. METHODS: Serum
      sFas was assessed in 15 men with schistosomal cor pulmonale (age 32 +/- 10
      years), 15 men with chronic cor pulmonale secondary to COPD and 20 healthy men,
      matched for age. RESULTS: Serum levels of sFas were significantly higher in
      patients with schistosomal cor pulmonale (74 +/- 80 U/ml) than in patients with
      cor pulmonale due to COPD (15 +/- 10 U/ml) and normal subjects (19 +/- 11 U/ml, p
      < 0.001 in both). In patients with schistosomal cor pulmonale, sFas was
      significantly higher in patients with mean pulmonary artery pressure > 30 mm Hg
      as compared to patients with pressure < or = 30 mm Hg (109 +/- 97 vs. 34 +/- 20
      U/ml, p = 0.01). There was a significant correlation between serum sFas and the
      mean pulmonary artery pressure in patients with bilharzial cor pulmonale (r =
      0.4, p < 0.01), but not in patients with COPD (r = 0.1, p = NS). CONCLUSIONS:
      Serum sFas levels are elevated in patients with schistosomal cor pulmonale and
      they are related to the severity of pulmonary hypertension. These findings
      suggest a role of apoptosis in schistosomal cor pulmonale.

PMID- 14732787
TI  - Shuttle walking test and 6-minute walking test induce a similar cardiorespiratory
      performance in patients recovering from an acute exacerbation of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The incremental shuttle walking test (SWT) has recently been proposed
      as a more valid and reproducible alternative to the conventional 6-min walking
      test (6MWT) in the evaluation of exercise tolerance in patients with chronic
      obstructive pulmonary disease (COPD). OBJECTIVE: To compare the cardiorespiratory
      performance obtained during two sessions of SWT with that obtained during two
      sessions of 6MWT. METHODS: We examined 18 patients (forced expiratory volume in 1
      s: 48 +/- 14%) recovering from an acute exacerbation of COPD that had required
      hospitalization. In the same afternoon, each patient performed two SWT and two
      6MWT, with an interval of at least 30 min between each test; the sequence of the
      tests was randomized. RESULTS: Mean walking distance was greater in the second
      SWT test than in the first SWT. The changes from baseline in systolic blood
      pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index
      at the end of the test were similar between the two 6MWT and the two SWT. There
      was a highly significant correlation between walking distances measured during
      SWT and during 6MWT (rho: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with
      functional data of COPD. CONCLUSIONS: SWT, though being considered to be closer
      to a submaximal exercise test than 6MWT, does not induce a greater
      cardiorespiratory performance than 6MWT in patients recovering from acute
      exacerbation of COPD.

PMID- 14732788
TI  - Clinical relevance of inter-method differences in fat-free mass estimation in
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Evaluation of fat-free mass (FFM) is becoming recognised as an
      important component in the assessment of clinical status and formulation of
      prognosis in patients with chronic obstructive pulmonary disease (COPD).
      OBJECTIVE: The aim of this study was to determine whether potential differences
      in FFM estimation performed by air displacement plethysmography (ADP),
      bioelectrical impedance (BIE) and anthropometry (ANTHRO) would assume clinical
      significance. METHODS: Twenty-eight patients with moderate-to-severe COPD were
      submitted to FFM estimation by ADP, BIE and ANTHRO. FFM was then allometrically
      related to peak oxygen uptake (peak VO2) as determined by symptom-limited
      incremental cycle ergometry. RESULTS: We found that ANTHRO classified fewer
      patients as 'FFM-depleted' than the other two techniques (p < 0.05). Although
      mean biases of the BIE-ADP differences were close to zero, their 95% confidence
      limits extended as high as 5.9 kg (16%). The ANTHRO-based allometric exponents
      for peak VO2 correction of FFM, therefore, were typically higher than those
      obtained by the other two methods in both depleted and non-depleted patients
      (ANTHRO: 1.45-1.41, BIE: 0.97-1.18, ADP: 1.08-1.14, respectively). CONCLUSION: We
      conclude that between-method differences in FFM estimation can be sufficiently
      large to have practical implications in patients with moderate-to-severe COPD. A
      single method of body composition assessment, therefore, should be used for FFM
      estimation in these patients.

PMID- 14732789
TI  - Plasma and bronchoalveolar lavage fluid levels of endothelin-1 in patients with
      chronic obstructive pulmonary disease and pulmonary hypertension.
AB  - BACKGROUND: Secondary pulmonary hypertension (PH) and cor pulmonale are the major
      clinical cardiovascular complications affecting prognosis in patients with
      chronic obstructive pulmonary disease (COPD). It is also known that endothelin-1
      (ET-1) is a potent vasoconstrictor peptide produced by the pulmonary vascular
      endothelium, and ET-1 may be implicated in the pathogenesis of PH. OBJECTIVES:
      The purpose of this study was to investigate the presence of ET-1 in patients
      with COPD and to assess the correlation of ET-1 levels in the plasma and
      bronchoalveolar lavage (BAL) fluid (BALF) in COPD patients with or without PH.
      METHODS: Twenty-two patients with COPD and 15 healthy controls were enrolled in
      the study. Peripheral venous blood samples were collected in all patients and
      controls. BAL was obtained in COPD patients, and ET-1 levels were measured by
      radioimmunoassay in all plasma and BALF samples. RESULTS: Plasma ET-1 levels were
      2.46 +/- 0.55 and 1.70 +/- 0.42 pmol/dl in patients with COPD and controls,
      respectively (p < 0.0001). Sixteen of the 22 patients with COPD (73%) had PH
      established by echocardiography. The ET-1 level in these patients amounted to
      2.59 +/- 0.50 pmol/dl, and it was 2.10 +/- 0.54 pmol/dl in 6 patients with COPD
      without PH. In COPD patients with and without PH, BALF ET-1 levels were 0.19 +/-
      0.08 and 0.24 +/- 0.01 pmol/dl, respectively (p > 0.05). CONCLUSIONS: These
      results suggest that ET-1 is detectable in both the peripheral blood and BALF of
      COPD patients, but the levels do not statistically differ between patients with
      and without PH.

PMID- 14732790
TI  - Eotaxin level in induced sputum is increased in patients with bronchial asthma
      and in smokers.
AB  - BACKGROUND: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may
      play an important role in eosinophil recruitment. OBJECTIVES: To examine the
      relationship between eotaxin levels in the sputum and eosinophilic inflammation.
      METHODS: The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic
      patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels
      in the sputum were determined by ELISA and immunocytochemical analysis. RESULTS:
      Asthmatic patients had eosinophilia and smokers showed neutrophilia in their
      sputum. The eotaxin level in the sputum was significantly higher in smokers
      (median 412.5, range 91.1-872.2 pg/ml) and asthmatic patients (351.0, 185.0-928.0
      pg/ml) compared with non-smokers (123.2, 0-369.0 pg/ml; both p < 0.05). IL-5 was
      detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic
      patients. The percentage of eotaxin-positive cells was higher in smokers and
      asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells
      was significantly higher only in asthmatic patients (p < 0.05). CONCLUSIONS:
      These findings suggest that the elevated eotaxin level in the sputum does not
      always accompany the increase in eosinophils, and cooperation with another
      cytokine such as IL-5 may be required for the recruitment of eosinophils.

PMID- 14732791
TI  - Evaluation of arterial endothelin-1 levels, before and during a sleep study, in
      patients with bronchial asthma and chronic obstructive pulmonary disease.
AB  - BACKGROUND: Endothelin (ET)-1 has been implicated in the pathogenesis of asthma
      and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated
      during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and
      sputum, falling with treatment of the exacerbations. OBJECTIVE: The aim of this
      study was to examine the ET-1 blood levels in stable asthmatic patients and
      stable COPD patients during alertness and sleep. MATERIALS AND METHODS: We
      examined 48 COPD and 20 asthmatic patients. All underwent forced spirometry,
      measurement of SaO2 and of arterial ET-1 levels and nocturnal polysomnography. ET
      1 levels were also determined during nocturnal oxyhaemoglobin desaturation.
      RESULTS: The daytime SaO2 level of our asthmatic patients was higher than that of
      our COPD patients (p < 0.001). Daytime SaO2 level of our non-desaturator COPD
      patients was higher than that measured in desaturator COPD patients. Nightime
      SaO2 level in our asthmatic patients was higher than that in our desaturator COPD
      patients (p < 0.001). Daytime ET-1 levels in desaturator COPD patients were
      higher than those observed in normal individuals, in non-desaturator COPD
      patients and in asthmatic patients. The COPD desaturator patients had higher
      levels of ET-1 during nighttime than during daytime (p < 0.001). CONCLUSION:
      Asthmatic patients did not exhibit desaturation of haemoglobin during the night.
      ET-1 levels are significantly higher in desaturator COPD patients compared with
      non-desaturator COPD patients, both during the day and during the night. ET-1
      levels in stable COPD patients are significantly higher than in patients with
      stable asthma. These findings are consistent with the hypothesis that ET-1 is
      implicated in the pathogenesis of COPD and asthma.

PMID- 14732792
TI  - Newly diagnosed tuberculosis in inner-city Chicago: the pulmonary fellow
      perspective.
AB  - BACKGROUND: The extent to which pulmonary fellows encounter patients with newly
      diagnosed tuberculosis during their 3-year training program in large metropolitan
      areas in the USA where active tuberculosis is still relatively common is
      uncertain. OBJECTIVES: To characterize clinical encounters of pulmonary fellows
      with patients with newly diagnosed tuberculosis at a large university-based
      training program in inner-city Chicago over a 3-year period. METHODS: A
      retrospective review of medical records of patients with newly diagnosed
      tuberculosis at the University of Illinois Medical Center at Chicago outpatient
      clinics (UMC) and the City of Chicago Department of Public Health Uptown
      Neighborhood Health Center Tuberculosis Clinic (CDPH) between 1999 and 2001 was
      conducted. A pulmonary fellow encounter rate (PFER) was derived as the average
      number of patients with newly diagnosed tuberculosis seen by a pulmonary fellow
      per month over the 3-year study period in each institution. RESULTS: We found
      that 9 pulmonary fellows diagnosed, treated and followed all 80 patients with
      newly diagnosed tuberculosis seen at CDPH over the 3-year study period. By
      contrast, they evaluated only 14 patients with newly diagnosed tuberculosis and
      followed 2 of them regularly at UMC (p < 0.05). PFER was 2.96 at CDPH and 0.52 at
      UMC (p < 0.05). Adverse events ascribed to anti-tuberculosis drugs were observed
      more frequently in patients seen by pulmonary fellows at CDPH than at UMC (p <
      0.05). CONCLUSIONS: Pulmonary fellows are more likely to encounter patients with
      newly diagnosed tuberculosis at a designated tuberculosis clinic than at a
      university hospital in inner-city Chicago during their 3-year training.

PMID- 14732793
TI  - Acute phase reactants and cytokine levels in unilateral community-acquired
      pneumonia.
AB  - BACKGROUND: Bacterial infection of the lower respiratory tract initiates an acute
      inflammatory response. Regulation of the inflammatory response in bacterial
      pneumonia depends on a complex interaction between immune cells and inflammatory
      cytokines. OBJECTIVES: We investigated the initial levels of proinflammatory
      cytokines and acute phase reactants (APR), e.g. C-reactive protein (CRP), upon
      presentation of community-acquired pneumonia (CAP) in relation to clinical and
      laboratory indices of infection. METHODS: We prospectively studied 28 consecutive
      patients with unilateral CAP. Tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, IL-6 and IL-8 concentrations were measured by ELISA in
      both bronchoalveolar lavage (BAL) fluid and serum. RESULTS: The concentrations of
      IL1-beta and IL-6 in BAL fluid were found to be significantly higher in the
      involved lung than those in either the uninvolved lung (p = 0.008 and p = 0.012,
      respectively) or serum (p = 0.002 and p = 0.025, respectively). Serum CRP
      concentrations were increased compared to those in the involved and uninvolved
      lung in BAL fluid (p = 0.000 and p = 0.000, respectively). In serum and BAL from
      involved lung, IL-6 concentrations were higher in the systemic inflammatory
      response syndrome (SIRS) group than in the non-SIRS group (p < 0.05), whereas
      CRP, TNF-alpha, IL-1beta and IL-8 concentrations showed no difference between
      SIRS and non-SIRS. There was no significant correlation between the acute
      physiology and chronic health evaluation II score and the cytokines. CONCLUSIONS:
      Our results indicate that the CRP level is higher in the serum than in the BAL
      fluid in the lung, and that IL-6 is the most important cytokine for the
      determination of the severity of the disease.

PMID- 14732794
TI  - Continuous monitoring of oxygen consumption in patients undergoing weaning from
      mechanical ventilation.
AB  - BACKGROUND: The extubation or discontinuation of mechanical ventilatory support
      (MVS) is only the final step in the weaning process, and an improvement in the
      efficiency of the weaning process is required for more successful extubation or
      discontinuation of MVS. OBJECTIVE: To evaluate whether continuous monitoring of
      oxygen consumption (VO2) using the metabolic gas monitor is a useful predictor of
      failure to tolerate a weaning trial of reduced MVS. METHOD: Twenty adult patients
      meeting the criteria for weaning, who required MVS > or = 7 days and who were
      previously deemed to have failed weaning by their attending physicians. A weaning
      trial was defined as a 30-min period during the strengthening training of our
      standardized weaning protocol. The average VO2, respiratory rate (RR), tidal
      volume (TV), minute ventilation (VE) and energy expenditure (EE) were recorded in
      respiratory muscles for a stable period of 20 min at rest and for the last 5 min
      of the trial. Subsequently, the oxygen cost of breathing (OCOB), the ratio of
      respiratory frequency to tidal volume (f/VT), DeltaRR, DeltaTV, DeltaVE, and
      DeltaEE were calculated. RESULTS: Two hundred and eight weaning trials, including
      145 successful trials and 63 failed trials from 20 patients were evaluated. In
      nonparametric analysis, a statistical difference in OCOB, DeltaRR, and DeltaEE
      was found between successful and failed weaning trials, while no statistical
      differences were found for the other parameters. An OCOB < 30% was the most
      accurate predictor of outcome of a weaning trial, and an f/VT < 105 was the least
      accurate. In a multiple logistic analysis, the OCOB revealed the highest odds
      ratio among all parameters. CONCLUSIONS: Measuring the OCOB was clinically
      beneficial in avoiding the induction of an excessive movement load on the
      respiratory muscles. In patients treated with MVS, continuous monitoring of VO2
      is a useful to predict success or failure of trials attempting to reduce MVS.

PMID- 14732795
TI  - Diagnostic yield of transbronchial histology needle aspiration in patients with
      mediastinal lymph node enlargement.
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA) is a safe, minimally invasive
      technique to assess the mediastinal spread of lung cancer. Excellent results have
      been published by experts. However, little information is available about the
      diagnostic yield of TBNA with the histology needle in a non-expert center.
      OBJECTIVES: The aim of this study is to assess the diagnostic yield of histology
      TBNA in the workup of suspected lung cancer. METHODS: In a non-university
      teaching hospital, TBNA data from patients diagnosed with lung cancer between
      June 1998 and July 2000 were analyzed retrospectively. TBNA had been performed by
      six different bronchoscopists in patients eligible for surgery with accessible N2
      and N3 lymph nodes on computed tomography of the chest during the workup of an
      undefined mass. Cytology and histology specimens were obtained with the same 19
      gauge needle. TBNA results were considered to be diagnostic if cytologic or
      histologic examination revealed a malignant lesion or non-malignant lymphoid
      cells. However, TBNA outcome was called non-diagnostic if no representative cells
      were obtained. RESULTS: From a group of 264 consecutive lung cancer patients, 106
      (40%) patients were eligible for TBNA. In 79%, TBNA was diagnostic in cytology
      and/or histology specimens. Malignancy was demonstrated in 59% (63/106). In only
      32/106 patients (30%), a histologic core of tissue could be sampled. In 87.5% of
      these patients (28/32), TBNA was diagnostic. For cytology only, this number was
      slightly lower (75%, 56/74). In 12 cases, diagnostic TBNA was verified by
      mediastinoscopy: these diagnoses were concordant. The sensitivity is 65% if all
      non-confirmed cases are considered false negative. Ten mediastinoscopies were
      avoided because TBNA demonstrated contralateral N2 (= N3) disease. The routine
      use of TBNA during bronchoscopy in suspected N2 disease is a cost-effective
      procedure, as the total additional costs of TBNA (9,540 EUR) were lower than the
      costs of 10 avoided mediastinoscopies (15,500 EUR). No complications were
      observed. CONCLUSION: The diagnostic yield of TBNA relied mainly on cytology
      specimens, despite the use of a histology needle. Representative histology
      specimens could only be obtained in 28/106 patients (26%). Since TBNA was
      performed in a general hospital by different bronchoscopists, this procedure is
      useful in the workup of lung cancer patients with enlarged lymph nodes.

PMID- 14732796
TI  - Reduced fatigue in diaphragm muscle of merosin-deficient DY/DY dystrophic mice.
AB  - BACKGROUND: The muscular dystrophies comprise a heterogeneous group of disorders
      characterized by the absence of specific glycoproteins located at or near the
      cell membrane. The effects of dystrophin deficiency on diaphragm contractile
      function are well delineated, whereas the consequences of merosin (laminin
      alpha2) deficiency are not well defined. OBJECTIVES: Studies tested the
      hypothesis that genetic deficiency of merosin alters diaphragm fatigue
      resistance. METHODS: Diaphragm contractile performance was tested in vitro using
      DY/DY dystrophic mice, which have the same biochemical defect as human classic
      congenital muscular dystrophies. RESULTS: Twitch force/area was reduced by 46% in
      DY/DY dystrophic diaphragm, but isometric twitch kinetics were not altered.
      During repetitive 25-Hz stimulation, normal muscle demonstrated early force
      potentiation lasting 20 s. This was followed by a fast decline in force, with
      total force loss of approximately 45% over 2 min. Force of dystrophic diaphragm
      also increased at the onset of stimulation, but remained elevated over baseline
      values for up to 70 s. Force decline thereafter was slow, amounting to
      approximately 5% after 2 min and (in a subset of muscle samples stimulated for
      longer durations) approximately 20% after 5 min. Relaxation rate of normal muscle
      slowed considerably during repetitive stimulation, whereas that of DY/DY
      dystrophic diaphragm remained constant. CONCLUSIONS: Merosin deficiency increases
      diaphragm force potentiation and reduces fatigue despite considerable muscle
      weakness. We speculate that the former may be important for maintaining
      ventilatory homeostasis in the merosin-deficient muscular dystrophies.

PMID- 14732797
TI  - An extrathoracic cause for a unilateral hyperlucent lung on a chest radiograph.

PMID- 14732798
TI  - An adult case of Bochdalek hernia complicated with hemothorax.
AB  - A 53-year-old female with mild shock due to vomiting and abdominal pain visited
      the emergency room of our hospital. Chest X-ray on admission showed a large
      amount of left pleural effusion. Thoracentesis revealed hemorrhagic pleural
      effusion. An upper gastrointestinal series showed interruption of the upper
      gastric body, but the anal side was not visualized. Contrast X-ray examination of
      the thoracic cavity via the drainage tube demonstrated intrathoracic herniation
      through the diaphragm. These findings suggested gastric impaction in the foramen
      of Bochdalek, and thoracotomy was immediately performed. A black-colored stomach
      and greater omentum, suggesting necrotic changes, were observed in the thoracic
      cavity, and there was bleeding from the greater omentum. Resection of the
      necrotic organs and closure of the hernial orifice were followed by good
      recovery.

PMID- 14732799
TI  - Cavernous hemangiomas of lungs and liver in an asymptomatic girl.
AB  - We describe a 15-year-old asymptomatic girl with multiple pulmonary nodules which
      turned out to be cavernous hemangiomas. The radiological findings of other organs
      revealed no abnormalities, excluding the liver, where multiple low-density areas
      were located. Thoracoscopy and laparoscopy revealed cavernous hemangiomas of the
      lung and liver. While liver cavernous hemangiomas are common, pulmonary
      hemangiomas are fairly rare. Although cavernous hemangiomas are classified as
      malformations, some of these lesions have been reported to grow. In pulmonary
      hemangiomas, some cases have an inexorable clinical course with hemoptysis,
      respiratory distress, and heart failure. In our case, the lesions have not
      remarkably progressed under observation for more than 2 years.

PMID- 14732800
TI  - Coccidioidomycosis mimicking lung cancer.
AB  - A 65-year-old female smoker was admitted due to haemoptysis and a pulmonary
      infiltrate in the right lower lung lobe. Tumour was suspected, but there was also
      a history of 2 years spent in Arizona, known to be endemic for the dimorphic
      fungus Coccidioides immitis. IgG antibodies and airway culture for C. immitis
      were negative, and surgery was performed for suspected lung cancer. No malignancy
      was detected at histopathological investigation, but typical coccidioidal
      spherulae were observed by silver stain. Coccidioidoma may be a differential
      diagnosis to malignant tumour in individuals visiting endemic areas.

PMID- 14732801
TI  - A young healthy woman presenting with acute meningitis and a large pleural-based
      mass.

PMID- 14732802
TI  - Methodological aspects of bronchoscopic lung volume reduction with a proprietary
      system.
AB  - Bronchoscopic lung volume reduction (BLVR) is emerging as a new technique to
      palliate symptoms in patients with severe emphysema. Several devices and
      techniques are being developed to occlude airways resulting in collapse and
      reduced lung volume. Here we present in detail the methodological aspects of one
      such interventional bronchoscopic approach.

PMID- 14732803
TI  - Inflammation and obstructive sleep apnea syndrome pathogenesis: a working
      hypothesis.
AB  - Obstructive sleep apnea syndrome (OSAS) afflicts about 5% of adults in Western
      countries and is thought to play an important role in the pathogenesis of
      cardiovascular disorders and diabetes mellitus. Although the etiology of OSAS is
      uncertain, intense local and systemic inflammation are present in these patients.
      In the upper airway, this process may promote oropharyngeal inspiratory muscle
      dysfunction and amplify upper airway narrowing and collapsibility thereby
      worsening the frequency and duration of apneas during sleep. The presence of
      systemic inflammation, characterized by elevated levels of certain potent pro
      inflammatory mediators, such as C-reactive protein, leptin, TNF-alpha, IL-1beta,
      IL-6, reactive oxygen species and adhesion molecules, may predispose to the
      development of cardiovascular complications observed in patients with OSAS.
      Treatment with nasal CPAP abrogates, in part, local and systemic inflammation in
      these patients. Whether therapeutic interventions aimed at abating inflammation
      could be a useful adjunct in the treatment of OSAS merits further investigation.

PMID- 14732804
TI  - Profound hypokalemia in acute respiratory failure: a diagnostic dilemma.

PMID- 14732805
TI  - The drumbeat of renal failure: symbiosis of prevention and renal replacement
      therapy.
AB  - The global population of patients with end-stage renal disease is rising rapidly,
      especially in developing countries. The possibility and economic burden of renal
      replacement therapy will be greatly challenged in the next decade as the
      prevalence of diabetes and hypertension rises. The establishment of effective
      prevention and intervention measures creates a means by which the increasing
      burden of renal replacement therapy can be reduced.

PMID- 14732806
TI  - Monocyte apoptosis in uremia is normalized with continuous blood purification
      modalities.
AB  - Uremia is associated with a state of immune dysfunction. Dysregulation of
      homeostasis may be directly related to abnormal apoptosis regulation in uremia,
      which is crucial for the maintenance of the biological system. We demonstrated
      that plasma from three groups of uremic subjects, i.e. hemodialysis (HD)
      patients, peritoneal dialysis (PD) patients and patients with predialysis chronic
      renal failure (CRF), has different apoptotic potential on U937 monocytes. The
      plasma of HD and CRF subjects when incubated with U937 cells induced higher
      levels of apoptosis compared with that of PD and control subjects (HD 26.08 +/-
      11.39, CRF 24.87 +/- 9.07, PD 12.13 +/- 4.51, controls 11.69 +/- 4.02).
      Furthermore, the phagocytic ability of U937 cells incubated with the various
      plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 +/-
      6.67, CRF 30.24 +/- 9.08, PD 36.55 +/- 9.80, controls 40.04 +/- 6.98). These
      results suggest that continuous blood purification, such as in PD, may have
      advantages over intermittent therapies in removing uremic apoptotic molecules and
      potentially maintaining biological function and homeostasis.

PMID- 14732807
TI  - International care models for chronic kidney disease: methods and economics-
      United States.
AB  - In the United States, there is a major chronic kidney disease (CKD) problem with
      over 8 million adults having stage 3 or 4 CKD. There is good medical evidence
      that many of these patients can benefit from focused interventions. And while
      there are strong theoretical reasons to believe these interventions are cost
      effective, there are little published data to back up this assertion. However,
      despite the lack of financial data proving cost-effectiveness and against the
      background of a disorganized health care system in the US, some models of CKD
      care are being employed. At the present time, the most comprehensive models of
      care in the US are emerging in vertically integrated health care programs. Other
      models of care are developing in the setting of managed care health plans that
      employ CKD disease management programs, either developed internally or in
      partnership with renal disease management companies.

PMID- 14732808
TI  - Cardiac disease in chronic kidney disease: current understandings and
      opportunities for change.
AB  - Cardiovascular disease (CVD) is prevalent in patients with kidney disease: in
      populations prior to dialysis, on dialysis and after transplantation.
      Publications over the last decade have focused on this, and more recently,
      patients with cardiac disease are now recognized as being at increased risk in
      the presence of even mild kidney dysfunction. The presence of both traditional
      and non-traditional risk factors contributes to this overwhelming burden of
      cardiovascular disease in patients with chronic kidney disease (CKD). Recent
      studies have focused on the impact of anemia and disorders of mineral metabolism
      on CVD outcomes, in the context of inflammation and evidence of cytokine
      activation. Cross-sectional and prospective observational studies have led to
      improved understanding, and generated novel hypotheses. To date, no clinical
      trial has determined the positive impact of interventions targeted at these novel
      risk factors. This overview describes the current state of knowledge and
      emphasizes the interplay between CVD and CKD as two aspects of a set of
      pathophysiological processes, which impact on patient outcomes.

PMID- 14732809
TI  - Atherosclerosis in dialyzed patients.
AB  - In the recent HEMO study, the most common cause of death in dialyzed patients was
      ischemic heart disease. In Europe there are regional differences, but the
      mortality due to cardiovascular disease is also very high. The long-lasting
      controversy whether the high incidence and prevalence of atherosclerotic
      manifestations (particularly ischemic heart disease) may be explained by known
      risk factors, or non-traditional risk factors are also involved seems to be
      partially solved with the increasing evidence that the latter hypothesis is true.
      Thus, together with classic risk factors such as hypertension, dyslipidemia and
      diabetes, other situations such as microinflammation, increased concentration of
      asymmetrical dimethyl-L-arginine, disturbed phosphate metabolism and anemia may
      represent important risk factors for accelerated atherosclerosis in dialyzed
      patients.

PMID- 14732810
TI  - Calcimimetics versus vitamin D: what are their relative roles?
AB  - A strict control of secondary hyperparathyroidism in patients with chronic kidney
      disease (CKD) is indicated to avoid serious complications linked to osteitis
      fibrosa and other parathyroid-hormone (PTH)-related bodily disturbances. However,
      such a control is often achieved only at the price of unacceptably high plasma
      calcium and phosphorus levels and the risk of soft tissue calcification, even
      when using the novel, so-called 'non-hypercalcemic' vitamin D analogs. The advent
      of a new class of drugs, the calcimimetics, should allow a more adequate control
      of the disturbed calcium-phosphorus metabolism in CKD patients. In my opinion,
      the calcimimetics will not replace currently used medications but will be a
      valuable supplement to presently available treatment options for this major
      complication in patients with renal failure.

PMID- 14732811
TI  - Volume control in peritoneal dialysis patients: role of new dialysis solutions.
AB  - This paper reviews the most recent clinical data on the volume status of long
      term peritoneal dialysis (PD) patients. It appears that many PD patients are
      volume overloaded, associated with a high prevalence of hypertension and left
      ventricular hypertrophy. In the presence of the poor results in patients with
      peritoneal ultrafiltration, the introduction of the polyglucose solution,
      icodextrin, has ameliorated volume control in some of these patients. In a second
      part of the review, some of the structural and functional alterations in the
      peritoneal membrane and the role of glucose degradation products (GDP) in the
      commonly used dialysates as well as the resulting formation of advanced glycation
      end products are described. The introduction of low GDP-containing solutions at
      normal pH has at least in experimental models of PD attenuated the hemodynamic
      changes observed with the classical solutions. The solutions at normal pH
      containing either bicarbonate or a mixture of bicarbonate/lactate were clinically
      associated with less inflow pain.

PMID- 14732812
TI  - Role of sodium and volume in the pathogenesis of hypertension in dialysis
      patients. Reflections on pathophysiological mechanisms.
AB  - Volume and sodium excess is the predominant factor in the pathogenesis of
      hypertension in dialysis patients. However, except for anephric patients, the
      relationship between volume status, blood pressure, and hemodynamics is not
      straightforward, but may vary between subgroups of patients. In general, the
      sensitivity of blood pressure to changes in the volume/sodium status appears to
      be increased in patients with end-stage renal disease. The blood pressure
      response to changes in the sodium/volume status may be influenced by disturbances
      in the activity of and response to various neurohumoral mechanisms, such as the
      renin-angiotensin and sympathetic nervous systems, Na-K-ATP-ase inhibitors, and
      the nitric oxide system. Regarding these aspects, there might be a parallel with
      salt-sensitive (essential) hypertension. Preliminary data showed a beneficial
      effect of sodium removal beyond changes in the volume status. Also of interest is
      the fact that prolonging dialysis time may improve blood pressure control without
      clear changes in the fluid status. It is hypothesized that a reduction in
      exchangeable sodium, by increased diffusive transport of sodium, in combination
      with increased removal of vasopressor substances, might be partly responsible for
      the observed blood pressure changes during long dialysis times. In conclusion,
      sodium and volume overload and neurohumoral factors coincide in the pathogenesis
      of hypertension in dialysis patients. Nevertheless, their exact relationship has
      not yet been elucidated and deserves further study.

PMID- 14732813
TI  - Renal cell therapy in the treatment of patients with acute and chronic renal
      failure.
AB  - Hemodialysis and hemofiltration have been important technologies in saving the
      lives of patients with acute (ARF) and chronic renal failure by clearing small
      solutes from plasma and thereby preventing death from acidemia, hyperkalemia,
      volume overload, and uremia. These therapeutic approaches, however, are still
      suboptimal, as patients with ARF have mortality rates exceeding 50%, and patients
      with end-stage renal disease (ESRD) have, on average, a life expectancy of 4-5
      years. The preeminent cause of death in patients with ARF is the development of
      sepsis or the systemic inflammatory response syndrome with resulting systemic
      vasodilation, hypotension, ischemic injury to solid organs, multi-organ failure,
      and death. This vasodilation is due to persistent and excessive pro-inflammation.
      Similarly, the reduced survival times of patients with ESRD on chronic dialysis
      have been associated with a persistent and chronic systemic pro-inflammatory
      state. We have hypothesized that the loss of renal tubule cell mass acutely in
      acute tubule necrosis and chronically in ESRD results in an immunologically
      dysregulated state leading to excessive pro-inflammation. The replacement of
      renal tubule cell function may thus change the current dismal prognosis of
      patients with these disorders. In this regard, this report presents the first
      patient ever treated with a bioartificial kidney consisting of a synthetic
      hemofilter in series with a renal tubule assist device (RAD) containing
      approximately 10(9) human renal tubule cells. This treatment in a critically ill
      patient with multi-organ failure and ARF in the intensive care unit was
      associated temporally with improved cardiovascular parameters and enhanced native
      kidney function. Multiple systemic plasma cytokine levels and gene expression
      profiles of peripheral white blood cells were also temporally changed with cell
      therapy. Clinical trials in patients suffering from either ARF or ESRD are
      currently ongoing to evaluate the influence of the RAD on the inflammatory
      response in these groups of patients.

PMID- 14732814
TI  - Sorbents in acute renal failure and end-stage renal disease: middle molecule and
      cytokine removal.
AB  - Renal replacement therapy in acute renal failure (ARF) and chronic renal failure
      (end-stage renal disease; ESRD) has been based on the use of modifications of
      dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to
      remove middle-molecular-weight toxins, consisting of low-molecular-weight
      proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux
      dialyzers are not efficient at removing LMWP, and for this reason, sorbents have
      been studied to augment or replace dialysis. Removal of LMWP such as beta2
      microglobulin, leptin, complement factor D, angiogenin and cytokines such as
      interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-alpha has been
      established in animal models of sepsis and in ESRD patients using sorbents.
      Sorbent devices added to hemodialysis, or the use of such devices alone in
      inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre
      explantation of donor organs and ESRD, are being studied.

PMID- 14732815
TI  - Non-specialist ultrasound measuring of access flow: new technology.
AB  - A new ultrasound instrument has been developed, using vector Doppler and embedded
      machine intelligence, to enable measurement of access flow rates by non
      specialists. Ultrasound measurement of access flow can be performed with the
      patient off the dialysis machine, avoiding the hemodynamic changes that may
      affect indicator-dilution methods. A research version of the instrument was
      tested on flow phantoms simulating graft flow, and showed accuracy better than
      5%. A non-specialist measured flow in the access grafts of 7 consenting dialysis
      patients; the instrument showed flows commensurate with indicator-dilution
      measured flows, but with less variability. Measurements were made in less than 5
      min per patient. The cost per measurement is calculated to be significantly less
      than that of present methods of measuring flow. The new instrument may become a
      useful tool for monitoring flow in accesses to extend their life.

PMID- 14732816
TI  - Mathematical model of the effect of affinity hemodialysis on the T-cell depletion
      leading to AIDS.
AB  - HIV-derived envelope proteins appear to be intimately involved in the destruction
      of uninfected T cells that leads to AIDS in a process known as the 'bystander
      effect'. Affinity hemodialysis has been proposed as an effective means of
      reducing these viral toxins. Using deterministic mathematical models based on the
      well-known Perelson formulations, the effectiveness of affinity hemodialysis in
      reducing the levels of viral gp120 was analyzed. Incorporating experimental data
      on the function of the affinity dialysis system and data from published analyses
      of HIV viral dynamics, two different models of HIV and AIDS were analyzed. Both
      models predict a rapid and sustained reduction in gp120 levels. In the model
      incorporating stem cell dynamics, affinity hemodialysis treatment under several
      different scenarios was associated with a significant increase in T-cell levels
      independent of any release from lymphatic tissues. The calculations support the
      contention that affinity hemodialysis is a potentially useful adjunctive therapy,
      which can be employed to treat HIV-infected patients in conjunction with drug
      therapy. For those patients resistant to anti-retroviral drugs or those unable to
      take the drugs due to the side effects of those medications, affinity
      hemodialysis treatment may become a viable option.

PMID- 14732817
TI  - Dialysis without membranes: how and why?
AB  - Dialysis between two flowing, miscible fluids without an intervening membrane
      enhances both the transport rate and biocompatibility. Unfortunately, it also
      presents serious challenges, including the loss of pressure as a driving force
      for volume transport, the need for sterile dialysate in greater quantity than in
      conventional dialysis, the possibility of unacceptable protein loss, and even the
      possibility of blood cell loss. This paper quantifies these advantages and
      disadvantages, and evaluate the means by which the latter might be surmounted.
      Preliminary data are provided to show that stable flows of one fluid sheathing
      another, miscible fluid are achievable and that molecular exchange between the
      fluids is orderly and in qualitative agreement with the theory. Extension of the
      concept to other blood purification tasks, especially in the treatment of liver
      failure and various macromolecular separations, is also discussed. In conclusion,
      membraneless separations will require a secondary process and a recycle stream.
      Under these conditions, its advantages can be preserved and its disadvantages
      controlled.

PMID- 14732818
TI  - Polymorphism of immunomodulatory cytokine genes: implications in acute renal
      failure.
AB  - Experimental studies have incriminated cytokines and other immunoregulatory
      molecules as important mediators of tissue injury in acute renal failure (ARF).
      The relative importance of genetic factors, e.g. polymorphisms involving cytokine
      genes, in influencing susceptibility to and severity of ARF is unknown. This
      review summarizes the existing experimental and clinical studies supporting the
      role of inflammation in ARF, and critically examines human studies that have
      examined polymorphism of two critical cytokine genes, tumor necrosis factor-alpha
      and interleukin-10, as potential determinants of susceptibility to and severity
      of acute infectious and inflammatory diseases. Conclusions are drawn on the
      application of genetic epidemiology to the field of ARF and the rationale for
      further research on the role of genetic markers in ARF.

PMID- 14732819
TI  - Iron requirements in hemodialysis.
AB  - The correction of anemia in dialysis patients with erythropoietin (EPO) can be
      frustrated by insufficient iron. To address this effect, we preloaded candidate
      EPO patients with intravenous iron in the early 1990s. Preloading with 900-1,525
      mg of iron yielded the following results: 70% of patients had increasing
      hematocrits (HCTs) without EPO, and 40% of patients had HCTs greater than 30%.
      Apparent lack of iron led to blood loss studies. Routes evaluated were blood
      sampling, dialyzer clotting, blood in the dialyzer circuit and postdialysis
      bleeding. Projected annual losses were between 2,516 and 5,126 ml, depending on
      circuit and posttreatment losses. In terms of red cell loss, the results are
      comparable to those in the early days of dialysis before the introduction of
      current technology. Extension of these studies to daily dialysis predicts
      possible losses with this 6 times a week therapy of between 4,663 and 9,884 ml
      per year.

PMID- 14732820
TI  - When good water goes bad: how it happens, clinical consequences and possible
      solutions.
AB  - Dialysis fluid produced by state-of-the-art water preparation and distribution is
      contaminated with gram-negative bacteria and cytokine-inducing substances (CIS)
      derived from these microorganisms. The presence of a biofilm increases the risk
      of continuous contamination of dialysis fluid. Depending on the type of dialyzer
      membrane (cellulosic vs. synthetic) and the mode of dialysis (low flux vs. high
      flux with backfiltration), CIS may penetrate intact dialyzer membranes, induce
      cytokine production in the patient's blood and contribute to chronic inflammation
      associated with long-term hemodialysis therapy. Measures to improve the
      microbiological quality of dialysis fluid are: (1) the awareness of the problem
      and regular testing of dialysate samples using adequate methods; (2) disinfection
      of the entire water preparation and distribution system on a regular basis,
      replacement of biofilm-containing tubings, and (3) installation of ultrafilters
      in the dialysate circuit in particular when high-flux hemodialysis modalities are
      performed.

PMID- 14732821
TI  - Diabetes and chronic kidney disease: tragedy and challenge.
AB  - Management of hypertension in diabetic nephropathy is challenging and generally
      requires a minimum of three different and complementary antihypertensive agents
      to achieve the recently recommended blood pressure (BP) goal of <130/80 mm Hg in
      order to reduce cardiovascular (CV) risk and preserve kidney function. Commonly
      used antihypertensive combinations include an angiotensin-converting enzyme
      inhibitor or an angiotensin receptor blocker, agents that have compelling
      indications for use in diabetic renal disease, added to a diuretic, generally a
      thiazide-type agent. If additional therapy is required, either a beta-blocker or
      calcium antagonist may be added. Beta-blockers are particularly effective in
      people with a high sympathetic drive, i.e. high pulse rates, to lower BP and
      reduce CV risk while reducing proteinuria and slowing decline of kidney function.
      In light of this information, it is disturbing that a recent analysis of the
      NHANES III database indicates that only about 11% of people with diabetic kidney
      disease have achieved the target BP of <130/80 mm Hg. Recent data from Denmark
      demonstrate that focusing on total CV risk reduction among people with diabetes,
      including achievement of recommended BP and lipid goals along with the use of
      aspirin, exercise and a proper diet, can reduce the absolute risk of a CV event
      by 20% over less intensive treatment.

PMID- 14732822
TI  - Chronic kidney disease and sudden death: strategies for prevention.
AB  - The association between chronic kidney disease and cardiovascular death is
      accounted for, in part, by higher rates of serious arrhythmias. Research shows an
      independent relationship between worsened renal function and atrial fibrillation,
      heart block, ventricular tachycardia, ventricular fibrillation, and asystole.
      These higher rates also associate with underlying structural heart disease
      including left ventricular hypertrophy, cardiac fibrosis, valvular disease, and
      left ventricular systolic and diastolic dysfunction. In addition, chronic
      intermittent ischemia is implicated in the arrhythmias observed during
      hemodialysis. The superimposed conditions of acidosis and fluxes in both
      potassium and magnesium also contribute to higher rates of arrhythmias. Baseline
      estimated glomerular filtration rate is linked to worsened outcomes and increased
      defibrillation thresholds in patients receiving implantable cardioverter
      defibrillators. Preventive strategies include meticulous management of
      electrolytes, baseline treatment for cardiovascular disease, and when indicated,
      implantable cardioverter defibrillators. Future research into the mechanisms and
      prevention of sudden cardiac death in patients with chronic kidney disease is
      warranted.

PMID- 14732823
TI  - Hemoadsorption to improve organ recovery from brain-dead organ donors: a novel
      therapy for a novel indication?
AB  - While brain-dead organ donors represent the majority of the organ donor pool, it
      appears that graft survival is adversely affected by brain death itself. Brain
      death has been shown to cause severe disturbances in the hormonal, hemodynamic
      and immunological homeostasis, which could in part be responsible for the
      inferior outcome of organs originating from brain-dead donors compared to living
      donors. Hemodynamic effects of brain death lead to a wide fluctuation in mean
      perfusion pressures, blood flow to the organs and systemic oxygen consumption,
      altering regional perfusion. In addition, a wide array of immunological changes
      has been shown to occur after brain death contributing to organ injury and
      hemodynamic instability. Recent studies have shown that brain death upregulates
      multiple lymphocyte- and macrophage-derived cytokines and the injured brain
      itself may be the source of proinflammatory factors such as S100B. This increased
      inflammatory response seen during and immediately after brain death has also been
      associated with poor allograft function. Furthermore, there is evidence to
      suggest that the massive inflammatory response seen in brain-dead donors could
      also lead to increased immunogenicity and accelerated allograft rejection after
      transplantation. Hence, we hypothesize that nonspecific downregulation of this
      inflammatory response by hemoadsorption could potentially lead to improved donor
      organ and allograft function. As a 'proof of concept' we tested the ability of a
      novel hemoadsorbent to remove S100B in vitro using two human glioblastoma cell
      lines. Our results indicate a >80% reduction in S100B after 2 h of circulation
      with the sorbent.

PMID- 14732824
TI  - Ultrafiltration in patients with hypervolemia and congestive heart failure.
AB  - Fluid overload may occur in patients with myocardial dysfunction and different
      clinical problems. Myocoardial dysfunction may be a consequence of heart
      dilatation with reduced contractility, ventricular stiffness with diastolic
      dysfunction or the consequence of myocardial injury or circulating myocardial
      depressant factors as seen in sepsis. In all cases, cardiac support can be
      achieved by the optimization of fluid balance, the reduction in organ edema and
      the restoration of desirable levels of pre- and afterload. Several reports have
      shown that myocardial elastance can improve after hemofiltration with restoration
      of adequate fluid balance. In such conditions, continuous extracorporeal therapy
      may result in remarkable cardiovascular stability with maintenance of hemodynamic
      parameters, including mean arterial pressure, heart rate and systemic vascular
      resistance. Such stability, which is achieved through the slow continuous
      ultrafiltration and continuous refilling of the intravascular volume from the
      interstitium, enables the stability of the circulating blood volume and the
      preservation of organ perfusion. This is also crucial for renal recovery during
      acute renal failure.

PMID- 14732825
TI  - Extracorporeal therapies in non-renal disease: treatment of sepsis and the peak
      concentration hypothesis.
AB  - In the setting of intensive care, patients with acute renal failure often present
      a clinical picture of the systemic inflammatory response syndrome (SIRS). SIRS
      can be caused by bacterial stimuli or by non-microbiological stimuli that induce
      a significant inflammatory response. When this response is exaggerated, the
      patient experiences multiple organ system failure and a condition of sepsis also
      defined as a systemic malignant inflammation. This is mostly characterized by an
      invasion of cytokines and other pro-inflammatory mediators into the systemic
      circulation where major biological effects take place, including
      vasopermeabilization, hypotension and shock. At the same time, the monocyte of
      the septic patient seems to be hyporesponsive to inflammatory stimuli to a
      certain extent. In this condition, the patient faces a situation of
      hyperinflammation but at the same time of immunodepression expressing a clinical
      entity defined as counter anti-inflammatory response syndrome. The general
      picture of the clinical disorder is therefore better characterized by an
      immunodysregulation than by a simple pro- or anti-inflammatory disorder. Due to
      the short half-life of cytokines and other mediators spilled over into the
      circulation, it is extremely difficult to approach the problem at the right
      moment with the right pharmacological agent. For these reasons, the peak
      concentration hypothesis suggests that continuous renal replacement therapies,
      due to their continuity and unspecific capacity of removal, might be beneficial
      in cutting the peaks of the concentrations of both pro- and anti-inflammatory
      mediators, restoring a situation of immunohomeostasis. Thus the patient may
      benefit from a lesser degree of immunodysregulation and he/she may restore a
      close-to-normal capacity of response to exogenous stimuli.

PMID- 14732826
TI  - DOPPS estimates of patient life years attributable to modifiable hemodialysis
      practices in the United States.
AB  - Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) allow
      estimation of the percentage of patients outside published hemodialysis
      guidelines and their associated mortality risk. We estimated the number of life
      years that could be gained from adherence to four of these guidelines and two
      other modifiable practices, i.e. dialysis dose, phosphate control, improved
      anemia, partial correction of serum albumin, reduced interdialytic weight gain
      and less use of catheters for vascular access. We extrapolated DOPPS data on
      these practices and guidelines to the US hemodialysis population for a 5-year
      projected period. Of the practices we examined, the highest relative risk of
      mortality was associated with having albumin <3.5 g/dl (relative risk=1.38,
      p<0.0001); 20.5% of the patients in the study fell outside the target range. The
      adjusted sum of the patient years attributable to all six practice patterns was
      143,617; a more conservative estimate, modeling life years potentially gained by
      bringing half of all patients outside targets within them, is 69,367. The
      magnitude of potential savings in life years should encourage greater adherence
      to guidelines and practices that are significantly associated with better
      survival.

PMID- 14732827
TI  - The problem of pain.
AB  - Pain problems, especially posttraumatic headache, are very common following head
      trauma. Pain may be the most significant problem, more disabling than any brain
      or other injuries, and interfering with aspects of cognition or other function.
      However, posttraumatic headache and most other chronic posttraumatic pain
      problems remain poorly understood. This article reviews fundamental issues that
      should be considered in understanding the nature of chronic pain including the
      distinction between acute and chronic pain; neurobiological distinctions between
      the lateral and medial pain system; nociceptive versus neuropathic or other
      central pain; sensitization effects; the widely accepted view of chronic pain as
      a multidimensional subjective experience involving sensory, motivational
      affective and cognitive-behavioral components; the problem of mind-body dualism;
      the role of psychosocial factors in the onset, maintenance, exacerbation or
      severity of pain; plus issues of response bias and malingering.

PMID- 14732828
TI  - Psychological, neuropsychological, and medical considerations in assessment and
      management of pain.
AB  - Pain is a common yet challenging problem, particularly following traumatic
      injuries to the head or neck. It is a complex, multidimensional subjective
      experience with no clear or objective measures; yet it can have a significantly
      disabling effect across a wide range of functions. Persisting misconceptions
      owing to mind-body dualism have hampered advances in its understanding and
      treatment. In this article, a conceptualization of pain informed by recent
      research and derived from a more useful biopsychosocial model guides discussion
      of relevant medical, psychological, and neuropsychological considerations. This
      pain process model explains chronicity in terms of hyperresponsiveness and
      dysregulation of inhibitory or excitatory pain modulation mechanisms. Related
      neurocognitive effects of chronic pain are examined and recommendations for
      minimizing its confounding effects in neuropsychological evaluations are offered.
      A biopsychosocial assessment model is presented to guide understanding of the
      myriad of factors that contribute to chronicity. A brief survey of general
      classes and samples of the more useful pain assessment instruments is included.
      Finally, this model offers a rational means of organizing and planning
      individually tailored pain interventions, and some of the most useful
      pharmacologic, physical, and behavioral strategies are reviewed.

PMID- 14732829
TI  - Clinical caveats on medical assessment and treatment of pain after TBI.
AB  - The diagnosis and management of pain in the patient with traumatic brain injury
      (TBI) can be difficult in light of the limitations imposed by the cognitive,
      language, and behavioral deficits. With patients in the acute rehabilitation
      setting, one must be vigilant for the often subtle signs and symptoms of pain.
      Causes more commonly seen in the population with TBI as a consequence of the
      injury itself include dysautonomia, neuropathic pain, spasticity, and heterotopic
      ossification. Headaches may be a consequence of TBI or associated with it for
      other reasons. Sources of pain associated with TBI include deep venous thrombosis
      and others. The reader is reminded that patients with TBI are subject to all the
      causes of pain that affect the general population.

PMID- 14732830
TI  - Psychological and neuropsychological integration in multidisciplinary pain
      management after TBI.
AB  - The intersection of traumatic brain injury and posttraumatic chronic pain poses a
      significant challenge for the health practitioner. Effective intervention
      requires psychological and neuropsychological evaluation, multidisciplinary
      teamwork, and an understanding of a wide range of pain disorders and their
      relationship to traumatic brain injury. Assessment must include documentation of
      both current functioning and premorbid history. Pain interacts with cognitive
      impairment, mood and anxiety disorders, dysinhibition syndromes, and personality
      disorders, posing significant diagnostic dilemmas and treatment challenges.
      Coordinated care requires multiple, ongoing interventions from a variety of
      specialists. Patient involvement, focusing on internal locus of control, mediates
      successful treatment.

PMID- 14732831
TI  - Occipital nerve blocks in postconcussive headaches: a retrospective review and
      report of ten patients.
AB  - Headaches are common following traumatic brain injuries of all severities. Pain
      generators may be in the head itself or the neck. Headache assessment is
      discussed. Diagnosis and treatment of cervical headaches syndromes and, in
      particular, occipital neuralgia are reviewed. Finally, a retrospective study of
      10 postconcussive patients with headaches who were treated with greater occipital
      nerve blocks is presented. Following the injection(s), 80% had a "good" response
      and 20% had a "partial" response. Occipital nerve block is a useful diagnostic
      and treatment modality in the setting of postconcussive headaches.

PMID- 14732832
TI  - Pain pathoetiology after TBI: neural and nonneural mechanisms.
AB  - Individuals recovering from traumatic brain injury (TBI) frequently experience
      acute and chronic pain. Their pain experience is the net effect of many
      interacting and very complex physiologic, biochemical, and psychological
      mechanisms involving both the peripheral and central nervous system. This article
      reviews the basics of neural mechanisms and pathways of pain after TBI, and
      discusses clinical implications. Numerous intracranial and extracranial tissues
      must be considered in the evaluation of pain after TBI, with the specific
      mechanism of trauma influencing the anatomic distribution of injuries. The
      differential diagnosis usually falls into one of the following pathoetiologic
      classifications: primary or secondary musculoskeletal, vascular, visceral, and
      neural pain syndromes.

PMID- 14732833
TI  - The annual congressional brain injury awareness fair.

PMID- 14732834
TI  - [Hairy-cell leukemia: 30 cases and a review of the literature].
AB  - From 1978 to 2002, 30 patients presenting hairy-cell leukemia were seen in two
      different hospitals. We reviewed clinical, biological and therapeutic data. At
      diagnosis, the median age was 67.8 years; 47% were clinically asymptomatic, 12
      patients had anaemia, 15 thrombocytopenia (platelets<100,000/mm3). A treatment
      was required for 29 patients. At the end of the study, 27 patients are alive and
      none died because of the disease. This study confirms the good prognosis of hairy
      cell leukemia, especially since the advent of new therapeutics such as purine
      analogs. Based on the results in this series, we examined the different aspects
      of the disease referring to diagnosis, treatment and prognosis.

PMID- 14732835
TI  - [Opinion of general and specialized physicians toward euthanasia. Results from
      the French survey on attitudes and practices against palliative care, 2002].
AB  - OBJECTIVES: To evaluate opinion of physicians about the legalization of
      euthanasia according to their professional characteristics, their attitudes
      toward morphine, their attitudes toward communication with end-of-life patients,
      and their perception of specific types of terminal care. METHOD: Univariate and
      multivariate analyses were carried out from data collected among 1.000 general
      practitioners, oncologists, neurologists and HIV specialists (French cross
      sectional survey on palliative care, 2002). RESULTS: 42.5% of physicians agreed
      with the statement that euthanasia should be legalized as it is already the case
      in the Netherlands. Inadequate prescription of morphine and calling terminal
      sedation as active euthanasia were associated with a favorable opinion toward
      legalization of euthanasia. CONCLUSION: Specific training on pain management and
      terminal sedation would help physicians to have a better view of the problem of
      euthanasia.

PMID- 14732836
TI  - [EGF receptors in urological cancer. Molecular basis and therapeutic
      involvements].
AB  - Many epithelial cancers have been found to overexpress the receptor to epidermal
      growth factor (EGFR) including head and neck, breast, colon, lung, prostate,
      kidney, ovary, brain, pancreas and bladder cancer. Because of the association of
      EGFR overexpression with overall poor prognosis in patients with cancer, a number
      of strategies to block or downregulate EGFR have been developed to inhibit tumor
      proliferation and improve clinical outcome. These include monoclonal antibodies
      directed against the EGFR such as IMC-C225 which specifically targets EGFR and ZD
      1839 (Iressa) capable of inhibiting EGFR tyrosine-kinase in vitro. This report
      will focus on antibodies that target EGFR in renal cell carcinoma, prostate
      cancer and bladder cancer.

PMID- 14732837
TI  - [Abdominal and digestive manifestations in systemic vasculitides].
AB  - Digestive involvement is frequent during the course of systemic small and medium
      sized vessel vasculitides. Clinical manifestations range from rapidly regressive
      abdominal pain to surgical manifestations associated with poor prognosis. These
      are usually associated with extra-abdominal signs, reflecting vasculitis
      activity. Isolated gastrointestinal involvement is observed in only 16% of these
      patients. The main clinical manifestations are common to all vasculitides
      (ischemia, bowel infarction and perforations, gastrointestinal hemorrhage due to
      mucosal ulcerations or aneurysmal ruptures), but some are more specific to one
      type (granulomatous ileo-colitis during Wegener's granulomatosis, eosinophilic
      colitis during Churg-Strauss syndrome). Gastrointestinal arteriography can be
      helpful for diagnosis, but has no prognostic value, likewise for the presence of
      ANCA. As there are no identified factors predictive of a surgical abdomen,
      therapy must be adapted individually, using steroids and immunosuppressive
      agents, generally cyclophosphamide. Prompt surgical and medical care of these
      seriously ill patients has lowered mortality from nearly 100% twenty years ago to
      approximately 23 to 56% currently.

PMID- 14732838
TI  - [Cluster headache].
AB  - Cluster headache is characterized by recurrent unilateral attacks of headache of
      great intensity and brief duration (15-180 minutes), accompanied by local signs
      and symptoms of autonomic dysfunction including conjunctival injection,
      lacrimation, nasal congestion, rhinnorrhea, forehead and facial sweating, miosis,
      ptosis or eyelid edema. Attacks occur in so-called cluster periods lasting for
      weeks or months. About 10% of patients have chronic symptoms with no period of
      remission. There are only two abortive treatments with proven efficacy:
      subcutaneous sumatriptan and nasal oxygen inhalation. Prophylactic treatment is
      often needed to reduce the daily frequency of attacks: verapamil in episodic
      cluster headache and lithium in chronic cluster headache.

PMID- 14732839
TI  - [Subacute motor neuropathy induced by T3 hyperthyroidism].
AB  - Subacute motor neuropathy involving bulbar nerves is an unusual complication of
      hyperthyroidism. Clinical and neurophysiologic follow-up of such patients has
      been rarely reported. We describe a 41-year-old Colombian patient who developed
      respiratory failure associated with motor neuropathy and severe weight loss. The
      major clinical features included diffuse amyotrophy, bilateral facial paresis,
      and fasciculations, suggesting motor neuropathy. Electromyography confirmed the
      presence of axonal neuropathy, with predominant motor involvement. Goiter with
      hypervascularization was noticed, associated with pure T3 hyperthyroidism (T3l=26
      pg/ml; N<3.8). The patient was given carbimazole which induced a severe skin
      vasculitis 10 days later. Carbimazole was stopped and replaced by
      propylthiouracile, which also induced vasculitis with secondary cardiac failure.
      Total thyroidectomy was then performed. General status improved rapidly as well
      as motor deficit, amyotrophy and pyramidal syndrome. Electromyographic
      abnormalities improved significantly within 3 months. This observation
      demonstrates that hyperthyroidism can produce motor axonal neuropathy, curable
      with radical surgery.

PMID- 14732840
TI  - Neurological manifestations of polyarteritis nodosa associated with the
      antiphospholipid syndrome.
AB  - The association between antiphospholipid syndrome (APS) and vasculitis is rare
      and continues to evoke great interest. We report a case with neurological
      manifestations of polyarteritis nodosa (PAN) and concurrent APS. Electromyography
      and neuromuscular biopsy of the limb showed an axonal polyneuropathy following
      obliteration and necrosis of medium sized arteries, initially suggesting PAN.
      This vasculitis was confirmed on visceral selective arteriography, with the
      presence of numerous aneurysms. Cerebral MRI revealed multiple cortical and
      subcortical signals in the fronto-parietal areas, corresponding to ischemic
      microvascular lesions of APS. This association was confirmed by the presence IgG
      anticardiolipid, the past medical history of skin necrotic lesions and central
      retinal obliteration. Pulse intravenous cyclophosphamide, oral prednisolone and
      curative anticoagulation led to stabilization for 8 months.

PMID- 14732841
TI  - [Antisynthetase syndrome. Three cases and a review of the literature].
AB  - Antisynthetase syndrome belongs to the idiopathic myositis group which includes
      pulmonary interstitial disease, arthritis, Raynaud's phenomenon, and  mechanic's
      hands , associated with the anti-Jo1 antibody. We report three cases of
      antisynthetase syndrome, and review the clinical characteristics, and prognosis
      factors dominated by interstitial pneumonia.

PMID- 14732842
TI  - Extra-anatomic bypass shunting in aorto-iliac occlusive disease. Clinical results
      and risk factors in a Belgian population.
AB  - We present a retrospective study of 38 patients undergoing axillofemoral bypass
      shunting (AXF, n=42, including 29 axillobifemoral (AXBF) and 9 axillo-unifemoral
      (AXUF)) from 1988 to 1998, for aorto-iliac occlusive disease (AOD). Six were
      excluded from the study as they did not meet entry criteria; the remaining 32
      patients were retained. All patients had histories of failed medical treatment.
      Indications for grafting were limb salvage (n=19), pain at rest (n=10), and high
      grade claudication (n=9). There were 28 males. Mean age was 73 years (range: 56
      86). Preoperative assessment, risk factors and early outcome were considered.
      Knitted Dacron and Gore-Tex prostheses were used. Indications for AXF was poor
      general status, locally hostile or septic abdomen. All the patients were symptom
      free early after surgery, with disappearance of pain at rest, improvement in
      trophic necrotic, and gangrenous lesions of the limbs, and better independence in
      walking ability. One patient died during the first 30 days (3% operative
      mortality). Most deaths occurred within 6 months due to causes unrelated to
      surgery, mainly in patients with comorbid conditions. AXF bypass is an acceptable
      procedure for high risk AOD patients or when conventional anatomic in situ repair
      is contraindicated.

PMID- 14732843
TI  - [Leptin and chronic inflammatory bowel disease: the human labyrinth].

PMID- 14732844
TI  - Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel
      diseases.
AB  - BACKGROUND: Leptin, a protein with a cytokine-like structure, is produced
      predominantly by adipocytes. It appears to play a key role in immune responses by
      increasing the secretion of Th1 and pro-inflammatory cytokines. As fat-wrapping
      is a characteristic feature of Crohn's disease (CD), and as increased leptin
      levels have been reported in animal models of intestinal inflammation, this study
      investigated whether mesenteric adipose tissue could be a source of leptin in
      human inflammatory bowel disease (IBD). AIM: To quantify the expression of leptin
      mRNA in mesenteric adipose tissue of patients with CD or ulcerative colitis (UC).
      METHODS: Specimens were obtained from mesenteric white adipose tissue close to
      healthy and inflammatory small intestine and/or colon in patients with CD or UC
      and, for controls, from apparently healthy mesentery of patients operated for
      carcinoma of the right colon. The expression of leptin mRNA was assessed by
      reverse transcription-competitive polymerase chain reaction. RESULTS: Leptin mRNA
      levels were significantly higher in mesenteric adipose tissue of CD and UC
      patients than in controls (P<0.05). In CD and UC, concentrations were not
      significantly different in mesenteric fat specimens, whether contiguous to
      macroscopically normal or grossly abnormal intestine. CONCLUSIONS: This study
      provides the first evidence of a novel abnormality of the mesentery of patients
      with IBD. Overexpression of leptin mRNA in mesenteric adipose tissue may
      contribute to (a) the inflammatory process, (b) enhancement of mesenteric TNF
      alpha expression in CD (as recently reported), and/or (c) the anorexia frequently
      reported during flares of IBD.

PMID- 14732845
TI  - [Colorectal cancer screening: a survey of French general practitioners].
AB  - AIM: To determine knowledge, beliefs, self-reported practices and wishes of
      French general practitioners regarding colorectal cancer screening before the
      start of an organized screening program. METHODS: A postal survey of the 600
      general practitioners of the Haut-Rhin area was made in 2002. RESULTS: Response
      rate was 62%. Eighty-five% asked routinely their patients about their family
      history of colorectal cancer. Colorectal cancer screening was routinely proposed
      by 92% of practitioners to individuals with a family history (86% with
      colonoscopy) and by 20% to individuals without family history (69% with faecal
      occult blood test). Seventy-five% did not know French consensus conference
      guidelines on colorectal cancer screening. Fifty-three% ordered routinely faecal
      occult blood testing, mostly for the screening of individuals with family history
      and for the evaluation of symptoms, mainly iron-deficiency anemia and weight
      loss. Seventy-seven% would explore with colonoscopy subjects with positive faecal
      occult blood test. Fifty-four% had personally undergone screening. Fifty-six%
      considered that mass screening could reduce a lot colorectal cancer mortality and
      most of them agreed with the forthcoming organized colorectal cancer mass
      screening program. CONCLUSIONS: Screening for colorectal cancer is ordered less
      often than screening for female cancers. General practitioners are unaware of
      current guidelines. Beliefs and practices vary considerably and faecal occult
      blood testing is often inappropriately prescribed. Medical education concerning
      screening is needed. Colorectal cancer screening guidelines and policy should be
      clarified in France.

PMID- 14732846
TI  - [Perineal lesions related to sport activities].

PMID- 14732847
TI  - [What's left for surgical treatment of portal hypertension in cirrhosis
      patients?].

PMID- 14732848
TI  - [Medical practices and expectations of general practitioners in relation to
      hepatitis C virus infection in the Auvergne region].
AB  - AIMS: To determine the medical practices and expectations of general
      practitioners concerning screening and management of hepatitis C in the Auvergne
      region. METHODS: A survey was sent by mail to 250 general practitioners. They
      were then contacted by telephone interviews. RESULTS: 94% of general
      practitioners answered the survey. Each physician diagnosed an average of 0.6 new
      cases of hepatitis C in 1999, and had a mean of 3.2 patients with HCV in their
      practice. Screening was performed by 91% of general practitioners if there was a
      history of blood transfusion, by 87% if there was a history of intravenous drug
      use, by 92% in case of increased serum amino transferase levels. Screening was
      less frequent in case of household contact and was only performed by 68% general
      practitioners or of asthenia by 52% of general practitioners. Liver biopsy seems
      to be the main obstacle for the management of hepatitis C patients which is due
      to a refusal of liver biopsy by the patient according to 55% of general
      practitioners, a fear of complications according to 25% of general practitioners.
      Sixty percent of general practitioners considered that liver biopsy was performed
      in less than 50% of patients with hepatitis C. Fifty three percent of general
      practitioner thought that hepatitis C network could be useful for increasing
      their knowledge. CONCLUSIONS: Liver biopsy refusal by the patient restricts the
      management and therapy of patients with hepatitis C infection. Increase formation
      still requisite by 60 percent of general practitioner.

PMID- 14732849
TI  - [Epidemiology and management of care of hepatitis C infection in the Poitou
      Charentes region in 1997 and 2000].
AB  - OBJECTIVES: A repeat cross-sectional survey was performed in 1997 and 2000 in the
      Poitou-Charentes district of France to compare screening and management of
      hepatitis C virus infection. METHODS: The "Hepatitis C Network" asked the
      biological laboratories in the region to provide anonymous results of serology
      tests performed during two two month periods at a 3 year interval. An
      epidemiological and follow-up questionnaire was sent to the medical practitioner
      who prescribed the test for all positive tests. RESULTS: More serology tests were
      prescribed in 2000 (7074) than in 1997 (6168). The access to screening differed
      significantly between the 4 counties of the district (P<0.0001). Sixty-nine and
      58 patients were first diagnosed respectively in 1997 and 2000. In 2000, these
      patients were younger (P=0.05) and were infected later (P=0.03). The risk factors
      were similar for the two periods. Respectively 23% and 26% underwent a liver
      biopsy, and 12% were treated. CONCLUSION: Screening improved after a press
      campaign, but there was no increase in the number of newly detected patients. In
      2000, one third of patients were still inadequately cared for.

PMID- 14732850
TI  - [Drainage-lavage and closure of a late esophageal perforation with
      esophagopleural fistula and encysted pleural effusion after endoscopic injection
      sclerotherapy for varices].
AB  - We report a case of late perforation of the thoracic esophagus with an
      esophagopleural fistula after endoscopic sclerotherapy for esophageal varices in
      a Child-Pugh B9 cirrhotic patient. The existence of a thoracic empyema without
      diffuse mediastinitis allowed management of the fistula by percutaneous drainage
      lavage and antibiotic therapy with subsequent closure of the esophageal wall
      defect and recovery from sepsis. This observation indicates that minimally
      invasive management of an esophageal perforation complicated by an esophago
      pleural fistula is possible in highly selected patients.

PMID- 14732851
TI  - [Osseous metaplasia in a colonic adenocarcinoma].
AB  - Osseous metaplasia is rare in tumors of the gastrointestinal tract. We report the
      case of a 76-year-old man presenting with an adenocarcinoma of the transverse
      colon containing osseous tissue. Calcifications were seen on the abdominal CT
      scan. Pathogenesis of the osseous metaplasia is still unknown.

PMID- 14732852
TI  - [Voluminous hepatomegaly in a young diabetic patient].
AB  - A young woman with type I diabetes mellitus, was hospitalized for a voluminous
      hepatomegaly associated with hepatocellular glycogen overloading suggesting
      Mauriac's syndrome. Two factors are involved in the physiopathology of this
      syndrome, hyperglycemia, and hyperinsulinemia which activates glycogenesis and
      inhibits glycogenolysis. The prognosis is normally favourable if diabetes is
      controlled.

PMID- 14732853
TI  - [Acute hyperalgic gastritis inaugurating disseminated varicella in an
      immunodepressed patient].

PMID- 14732854
TI  - [Metastatic duodenal gastrinoma and autoimmune atrophic chronic gastritis].

PMID- 14732855
TI  - [Intestinal intussusception and celiac disease: two cases].

PMID- 14732856
TI  - [Early obstructive colon after treatment of active refractory Crohn's disease
      with infliximab].

PMID- 14732857
TI  - [Biliary ascaris and intrahepatic lithiasis: a case report].

PMID- 14732858
TI  - [Acute ischemia of the small intestine due to periarteritis nodosa revealing
      hepatitis C viral cirrhosis].

PMID- 14732859
TI  - [Etifoxine chlorhydrate-induced acute hepatitis].

PMID- 14732860
TI  - [Dual function of NF-kappa B system during inflammation].

PMID- 14732861
TI  - [Functional bowel disorders and their treatment: treat to cure and care to
      understand].

PMID- 14732864
TI  - Stress-induced cigarette craving: effects of the DRD2 TaqI RFLP and SLC6A3 VNTR
      polymorphisms.
AB  - Animal models have long implicated dopamine in stress-induced craving for a
      variety of addictive substances. However, translational studies of dopamine,
      stress and craving in humans are lacking. Based on the animal literature, this
      study's objective was to test the hypothesis that cigarette smokers carrying
      specific variants in dopamine-related genes would have heightened levels of
      cigarette craving following exposure to a laboratory stressor. Cigarette craving
      induced by controlled exposure to a laboratory stressor was assessed in healthy
      adult smokers (n=108) recruited by advertisement. Significantly stronger stress
      induced cigarette craving was found for individuals carrying either the DRD2 (D2
      dopamine receptor gene) A1, or the SLC6A3 (dopamine transporter gene) nine-repeat
      allelic variants. Stress-induced craving was markedly higher for those carrying
      both alleles, compared to those with neither, consistent with the separate
      biological pathways involved (receptor, transporter). Findings provide strong
      support for the possibility that dopamine involvement in stress-induced craving
      well established in animal models also applies to humans, and suggest a potential
      genetic risk factor for persistent smoking behavior.

PMID- 14732865
TI  - Nuclear transport and cancer: from mechanism to intervention.

PMID- 14732866
TI  - The history of cancer epigenetics.

PMID- 14732867
TI  - Understanding SARS with Wolfram approach.
AB  - Stepping acquired immunodeficiency syndrome (AIDS), severe acute respiratory
      syndrome (SARS) as another type of disease has been threatening mankind since
      late last year. Many scientists worldwide are making great efforts to study the
      etiology of this disease with different approaches. 13 species of SARS virus have
      been sequenced. However, most people still largely rely on the traditional
      methods with some disadvantages. In this work, we used Wolfram approach to study
      the relationship among SARS viruses and between SARS viruses and other types of
      viruses, the effect of variations on the whole genome and the advantages in the
      analysis of SARS based on this novel approach. As a result, the similarities
      between SARS viruses and other coronaviruses are not really higher than those
      between SARS viruses and non-coronaviruses.

PMID- 14732868
TI  - Protein product encoded by a human novel gene E9730 enhances AP-1 activity
      through interacting with Jab1.
AB  - A novel human gene, named E9730 (a clone number of fetal liver cDNA library), has
      been identified from more than 14,000 expressed sequence tags (ESTs) based on our
      large scale sequencing of human fetal liver cDNA libraries. Although sequencing
      of this novel human gene indicates that it is a leucine zipper protein, the
      function of E9730 and its homongous genes among species is unknown yet. To find
      out physiological functional clue of E9730, the yeast two-hybrid system was used
      to screen the E9730-interacting protein(s), and one clone containing a cDNA
      insert with almost the entire coding sequence (amino acids 39 C335) of human Jab1
      (Jun-activating domain binding protein 1) that interacted specifically with E9730
      was identified. A specific association between Jab1 and E9730 was shown by co
      immunoprecipitation and co-localization experiments. Furthermore, the data
      indicated that E9730 appeared to enhance Jab1-induced AP-1 activity in a
      concentration-dependent manner and Jab1 may be involved in the intracellular
      signaling transduction from E9730 to AP-1.

PMID- 14732869
TI  - DNAskew: statistical analysis of base compositional asymmetry and prediction of
      replication boundaries in the genome sequences.
AB  - Sueoka and Lobry declared respectively that, in the absence of bias between the
      two DNA strands for mutation and selection, the base composition within each
      strand should be A=T and C=G (this state is called Parity Rule type 2, PR2).
      However, the genome sequences of many bacteria, vertebrates and viruses showed
      asymmetries in base composition and gene direction. To determine the relationship
      of base composition skews with replication orientation, gene function, codon
      usage biases and phylogenetic evolution, in this paper a program called DNAskew
      was developed for the statistical analysis of strand asymmetry and codon
      composition bias in the DNA sequence. In addition, the program can also be used
      to predict the replication boundaries of genome sequences. The method builds on
      the fact that there are compositional asymmetries between the leading and the
      lagging strand for replication. DNAskew was written in Perl script language and
      implemented on the LINUX operating system. It works quickly with annotated or
      unannotated sequences in GBFF (GenBank flatfile) or fasta format. The source code
      is freely available for academic use at http://www.epizooty.com/pub/stat/DNAskew.

PMID- 14732870
TI  - Expressional analysis of an EREBP transcription factor gene OsEBP-89 in rice.
AB  - OsEBP-89 gene encodes an ethylene responsive element binding protein (EREBP)
      transcription factor from rice (Oryza sativa). Northern blot analysis revealed
      that OsEBP-89 was expressed in root, stem, seeds, flowers and leaves of rice.
      Histochemical assay showed that GUS expressed mainly in phloem of vascular
      tissues of the root and stem transition region (RST), basal part of sheath roots,
      stem node and basal part of adventitious roots, also in endosperm of seeds in
      transgenic rice harboring OsEBP-89/GUS construct (pNSG). A sequence of region
      from  C279 to  C97 was found to play an important role for OsEBP-89 genes
      expression though promoter deletion assay. The possible function of OsEBP-89 gene
      was discussed.

PMID- 14732871
TI  - Purification, gene cloning and expression of an acidic phospholipase A2 from
      Agkistrodon shedaoensis Zhao.
AB  - A protein with the activity of phospholipase A(2) named asAPLA(2) was purified to
      homogeneity from the venom of Agkistrodon shedaoensis Zhao through DEAE-Sepharose
      CL-6B anion exchange column, Source S, and Mono Q FPLC. Its molecular weight was
      estimated to be 19 kD by SDS-PAGE, and its pI was about 3.5 by IEF analysis. It
      inhibited the platelet aggregation that was induced by 1 micromol/ L ADP, and the
      IC(50) was determined to be 6 micromol/L. Degenerating primer was designed and
      synthesized according to the N-terminal amino acid sequence of asAPLA(2). Its
      full-length cDNA was cloned by RT-PCR from the total RNA extracted from the snake
      venom gland. Its molecular weight and the pI are determined to be 13,649 and 4.39
      respectively as calculated by DNAclub and DNAstar software according to the
      deduced amino acid sequence. Then the gene was cloned into the expression plasmid
      pET-40b(+) and expressed in E. coli BL21(DE3). Western blot analysis indicated
      that the expressed protein cross-reacted with the antibody against the native
      enzyme.

PMID- 14732873
TI  - DNA vaccine of SARS-Cov S gene induces antibody response in mice.
AB  - The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is
      one of the most important antigen candidates for vaccine design. In the present
      study, three fragments of the truncated S protein were expressed in E.coli, and
      analyzed with pooled sera of convalescence phase of SARS patients. The full
      length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The
      mouse serum IgG antibody against SARS-CoV was measured by ELISA with E. coli
      expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The
      results showed that all the three fragments of S protein expressed by E.coli was
      able to react with sera of SARS patients and the S gene DNA candidate vaccine
      could induce the production of specific IgG antibody against SARS-CoV efficiently
      in mice with seroconversion ratio of 75% after 3 times of immunization. These
      findings lay some foundations for further understanding the immunology of SARS
      CoV and developing SARS vaccines.

PMID- 14732872
TI  - A novel missense mutation (L296 Q) in cholesteryl ester transfer protein gene
      related to coronary heart disease.
AB  - Cholesteryl ester transfer protein (CETP) is a key participant in the reverse
      transport of cholesterol from the peripheral tissues to the liver. To understand
      further the role that CETP gene plays in the pathogenesis of coronary heart
      disease (CHD), the promoter region, all 16 exons and adjacent intronic regions of
      CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD
      patients and 209 healthy volunteers by the combination of PCR, denaturing high
      performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing.
      A novel missense mutation in the CETP gene was identified. This mutation
      (L(296)Q) was caused by a T-to-A conversion at codon 296 of exon 10 which
      resulted in the replacing of the codon for leucine (CTG) with the codon for
      glutamine (CAG). Further studies found that there was a significant increase in
      the mutant allele frequency in the CHD patients compared with that in the
      controls (0.160 vs. 0.091,cgr;(2) = 9.014, P = 0.003), and the odds ratio to
      develop CHD was 1.83 for the (296)Q allele carriers vs. (296)LL homozygotes.
      Statistical analyses also demonstrated that the mutant (296)Q allele carrier
      patients displayed significantly higher total cholesterol (TC) and low density
      lipoprotein cholesterol (LDL-C) concentrations than noncarrier patients. All
      these results suggest that the Q(296) mutation in CETP gene was closely related
      to CHD, and the identification of new mutations in the CETP gene will afford the
      opportunity to investigate the relationship between CETP gene and CHD.

PMID- 14732874
TI  - Interaction of plasminogen activator inhibitor-2 and proteasome subunit, beta
      type 1.
AB  - The apoptosis protection by plasminogen activator inhibitor -2(PAI-2) is
      dependent on a 33 amino acids fragment between helix C and D of PAI-2 which is
      probably may be due to the interaction of PAI-2 with unknown intracellular
      proteins. In this study we used the fragment between helix C and D of PAI-2 as
      bait to screen a HeLa cells cDNA library constructed during apoptosis in a yeast
      two-hybrid system and retrieved a clone that encodes 241 amino acids of
      proteasome (prosome, macropain) subunit, beta type 1(PSMbeta1) which plays
      important roles in NF-kappaB activation. GST-pulldown experiments confirmed the
      interaction between PAI-2 and PSMB1 in vitro. These data suggest that the
      antiapoptosis activity of PAI-2 is probably related to its interaction with
      PSMbeta1.

PMID- 14732875
TI  - Experimental study of rat beta islet cells cultured under simulated microgravity
      conditions.
AB  - To observe the effects of simulated microgravity on beta islet cell culture, we
      have compared the survival rates and the insulin levels of the isolated rat islet
      cells cultured at the micro- and normal gravity conditions. The survival rates of
      the cells cultured were determined by acridine orange-propidium iodide double
      staining on day 3, 7 and 14. The morphology of the cells was observed by electron
      microscopy. Insulin levels were measured by radioimmune assays. Our results show
      that the cell number cultured under the microgravity condition is significantly
      higher than that under the routine condition (P<0.01). Some tubular structure,
      possibly for the transport of nutrients, were formed intercellularly in the
      microgravity cultured group on day 7 after the cultivation shown by transmission
      electron microscopy. There were also abundant secretion particles and
      mitochondria in the cytoplasma of the cells. Scanning electron microscopy showed
      there were holes formed between each islets, possibly the connecting points with
      the nutrients transport tubules. The microgravity cultured group also has the
      higher insulin levels in the media when compared with the control group (P<
      0.01). Our results indicate that microgravity cultivation of islet cells has
      advantages over the routine culture methods.

PMID- 14732876
TI  - Analysis of five differentially expressed gene families in fast elongating cotton
      fiber.
AB  - Using the suppression subtractive hybridization method, we isolated five gene
      families, including proline-rich proteins (PRPs), arabinogalactan proteins
      (AGPs), expansins, tubulins and lipid transfer proteins (LTPs), from fast
      elongating cotton fiber cells. Expression profile analysis using cDNA array
      technology showed that most of these gene families were highly expressed during
      early cotton fiber developmental stages (0 C20 days post anthesis, DPA). Many
      transcripts accumulated over 50-fold in 10 DPA fiber cells than in 0 DPA samples.
      The entire gene family --AGP, together with 20 individual members in other 4 gene
      families, are reported in cotton for the first time. Accumulation of cell wall
      proteins, wall loosening enzymes, microtubules and lipid transfer protein may
      contribute directly to the elongation and development of fiber cells.

PMID- 14732877
TI  - Expression of hepatitis C virus E2 ectodomain in E. coli and its application in
      the detection of anti-E2 antibodies in human sera.
AB  - The second envelope glycoprotein (E2) of hepatitis C virus has been shown to bind
      human target cells and has become a major target for the development of anti-HCV
      vaccines. Anti-E2 antibodies have been suggested to be of clinical significance
      in diagnosis, treatment and prognosis of hepatitis C. However, large-scale
      expression and purification of E2 proteins in mammalian cells is difficult. As an
      alternative, E2 fragment (aa 385 C730) with a four-amino-acid mutation (aa 568
      C571 PCNI to RVTS) was expressed as hexa-histidine-tagged full length protein
      [E2N730(m)] in E. coli and purified to over 85% purity. Purified E2N730(m) was
      specifically recognized by homologous hepatitis C patient serum in Western blot,
      suggesting that it displayed E2-specific antigenicity. Rabbit antiserum raised
      against E2N730(m) recognized E2 glycoproteins expressed in mammalian cells in
      Western blot. Purified E2N730(m) was used to detect anti-E2 antibodies in human
      sera and showed better specificity and sensitivity than previously reported C
      terminally truncated E2 fragment (aa 385 C565). Association between anti-E2
      antibodies in patient sera and HCV RNA status was also demonstrated using this E.
      coli-derived protein. E2N730(m) might serve as an inexpensive alternative to
      mammalian cell-expressed E2 proteins in clinical and research applications.

PMID- 14732878
TI  - Molecular cloning and characterization of human homeobox gene Nkx3.1 promoter.
AB  - Nkx3.1 is a prostate-specific homeobox gene related strongly to prostate
      development and prostate cancer. To study its regulation of transcription, 1.06
      kb 5' flanking region of Nkx3.1 gene and its 5' deletion mutants (861, 617, 417
      and 238 bp) were obtained by PCR and cloned into pGL(3)-basic, a promoter-less
      luciferase reporter vector, to examine their promoter activities driving the
      reporter gene transcription. pRL-TK, a Renilla luciferase reporter vector was
      used as internal control, and pGL(3)-control and pGL(3)-basic were used as
      positive and negative control respectively. The promoter activities were
      determined by dualluciferase reporter assay 48 h after pGL(3) constructs were
      cotransfected with pRL-TK into prostate cancer cell LNCaP. The results showed
      that dual-luciferase reporter assay (M(1)/M(2)) of pGL(3)-1.06 kb cotransfection
      with pRL-TK was 2.7, which was about 1.5-fold higher than that of pGL(3)-control
      cotransfection with pRL-TK and 50-fold higher than that of pGL(3)-basic
      cotransfection with pRL-TK. The results also showed that the relative activities
      (M(1)/M(2)) were 0.71, 0.84, 0.44 and 2.07 respectively for pGL(3)-861 bp, pGL(3)
      617 bp, pGL(3)-417 bp, pGL(3)-238 bp, the last one still had 80% promoter
      activity compared with pGL(3)-1.06 kb, which showed that deletion from 1.06 kb to
      238 bp had small effects on promoter activity. The conclusion was that the 238 bp
      fragment containing a TATA box and two CAAT boxes had strong promoter activity.
      However, the deletion from 1.06 kb to 861 bp reduced activity 3.8-fold while the
      deletion from 417 bp to 238 bp enhanced activity 4.7-fold, which indicated that
      these deleted sequences might contain some important positive or negative
      regulatory elements. It will be important to identify the elements within the
      Nkx3.1 promoter that contribute to regulation of the gene transcription in the
      future studies.

PMID- 14732879
TI  - Genetics of melanoma susceptibility.
AB  - Both genetic and environmental factors confer a significantly increased risk for
      cutaneous melanoma. This review discusses hereditary predisposition to the
      disease, focusing on the high-penetrance candidate genes INK4A/ARF and CDK4, and
      on pathogenetic mechanisms of mutations in those genes. As known mutations
      account for approximately 25 to 40% of melanoma families reported to date, it is
      clear that other melanoma genes and other mechanisms underlying predisposition
      remain to be discovered. Low penetrance susceptibility genes such as melanocortin
      1 receptor and their modifying effect, also in concert with UV radiation, are
      likely to be implicated. Recent reports on a new candidate locus on chromosome
      1p22 and somatic mutations in genes of the RAS-RAF-ERK signalling pathway raise
      interesting questions for further investigation.

PMID- 14732880
TI  - Adjuvant high-dose interferon-alpha therapy for high-risk melanoma.
AB  - The incidence of melanoma continues to rise at a rate greater than all other
      cancers. Survival in melanoma varies widely by stage, and is affected by a number
      of prognostic factors including tumour thickness, ulceration and lymph node
      involvement. New AJCC staging criteria adopted in the 6(th) edition reflect the
      prognostic value of tumour ulceration, the number of positive lymph nodes as a
      better prognostic indicator than the size of nodal metastasis, and the similar
      prognostic value provided by nodal, in-transit and local recurrences. It also
      recognises the pathologic information about staging provided by lymphatic mapping
      and sentinel lymphadenectomy. High-risk resected melanoma is defined as disease
      that after surgery is at higher than 40 to 50% risk of recurrence and death. The
      urgency to the effort to develop effective therapy for melanoma has led to a wide
      variety of approaches that have been tested over the years in the high-risk
      adjuvant setting. Among the many therapeutic modalities tested, the only agent
      that has shown a significant and reproducible benefit in terms of survival and
      relapse-free interval has been high-dose interferon-alpha2b. We here review the
      evidence that has led to the regulatory approval of this regimen, as well as
      ongoing studies using high-dose interferon-alpha in the high-risk adjuvant
      setting. We also present selected ongoing trials testing potential future
      therapies that may prove effective for patients with high-risk resected melanoma.

PMID- 14732881
TI  - Melanoma vaccines: achievements and perspectives.
AB  - In the past decade, the characterisation of tumour antigens recognised by T cells
      has revolutionised the cancer-vaccine approach, providing for the first time the
      opportunity to immunise patients against cancer by using well-defined antigens.
      Because melanoma is one of the prototypic immunogenic tumours, a number of early
      phase clinical trials have been conducted on melanoma. Some tumour regressions
      have been documented, mainly for patients with metastatic disease. Recent
      advances include new tools for monitoring the anti-cancer immune response and the
      development of adjuvants aimed at inducing a robust anti-melanoma immune
      response. Together, these developments should allow an optimal vaccination
      modality to be selected within the next few years.

PMID- 14732882
TI  - Biochemotherapy of melanoma.
AB  - Based on the observation of a small proportion of long-term responses the use of
      biotherapy or biochemotherapy is currently preferred in many institutions as
      first line treatment in stage IV melanoma, but still the outcome for patients
      with stage IV melanoma is unsatisfactory. Various interleukin 2 (IL-2) dosing
      schedules and combinations with interferon alpha (IFN-alpha) have been tested in
      patients with advanced melanoma in phase I and II studies. The response rate
      reported with cytokines alone (IL-2 as a single agent or in combination with IFN
      alpha) varies from 10-41%. Subsequently, biochemotherapy regimens combining IL-2,
      IFN-alpha and chemotherapy have been evaluated in phase II trials suggesting
      improved response rates. Recent randomised trials have investigated the role of
      biochemotherapy as compared to biotherapy alone or as compared to chemotherapy
      for the treatment of advanced melanoma. So far, none of the approaches has been
      proven to confer a survival benefit and thus the uniform desire is to include as
      many patients as possible into controlled clinical trials. Therefore current
      trials are under way trying to improve the efficacy of immunotherapy alone by
      adding histamine or vaccines to IL-2.

PMID- 14732883
TI  - Brain metastases from malignant melanoma.
AB  - Metastatic spread of tumour cells detached from melanoma into the central nervous
      system (CNS) occurs haematogenously since lymphatic drainage is absent in the
      brain. CNS metastases occur in 10 to 40% of melanoma patients in clinical studies
      and up to 90% in autopsy studies. Headache is the most common presenting symptom,
      but brain metastases should be suspected in all melanoma patients with new
      neurologic findings. Magnetic resonance imaging is the best diagnostic technique
      for detecting CNS metastases. Median survival of melanoma patients with CNS
      metastases ranges between 2 and 8 months. The optimal treatment of melanoma
      patients with CNS metastases depends on the objective situation, often surgery,
      radiosurgery, whole brain radiotherapy and chemotherapy are used in combination
      to obtain longer remissions and optimal symptom relieve.

PMID- 14732884
TI  - Guidelines for the management and treatment of low-grade gliomas.
AB  - Treatment options for low-grade gliomas are a challenging dilemma in neuro
      oncology. Young age at onset, low rate of growth and long-term treatment
      sequelae, indicate that minimally invasive treatments are required. However,
      local recurrence and conversion to malignant glioma occur within 4 to 8 yrs after
      diagnosis, calling for adjuvant treatment strategies, such as RT and chemotherapy
      with the aim of improving the disease-free interval. As glioma has a low
      incidence, and few randomised trials are available in literature, there is little
      consensus on the correct timing and dosage for RT, or on indications for timing
      and choice of cytotoxic drugs administration. The present paper therefore focuses
      on current concepts and future perspectives in the treatment options for low
      grade gliomas.

PMID- 14732885
TI  - Guidelines for the treatment of oligodendroglioma: an evidence-based medicine
      approach.
AB  - The sensitivity to chemotherapy of oligodendroglioma (OD) is the major clinical
      distinction between oligodendroglial and astrocytic tumours. In particular,
      chemotherapy with alkylating agents (PCV chemotherapy, temozolomide) in recurrent
      OD is of proven efficacy, with 50 to 70% of patients responding. The value of
      adjuvant chemotherapy in newly diagnosed tumours still remains to be proven. The
      efficacy of radiotherapy (RT) has never been proven in a phase III trial on OD,
      but based on historical phase III trials on anaplastic glioma this generally
      considered part of standard treatment of these tumours. Recent molecular
      biological studies show that OD are characterised by a combined loss of the short
      arm of chromosome 1 (1p) and the long arm of chromosome 19 (19 q). This combined
      loss of 1p and 19 q also identifies a group of tumours with a better response to
      chemotherapy and a longer survival after RT. It is expected that this knowledge
      will change the diagnostic criteria for OD and will help to select patients for
      specific treatments. However, improvement of the currently available treatments
      is needed, as the outcome of these patients remains dismal.

PMID- 14732886
TI  - Guidelines for the treatment of primary central nervous system lymphomas in
      immunocompetent patients.
AB  - The best therapeutic management in primary central nervous system lymphomas
      remains to be defined because of current knowledge on these malignancies results
      from small retrospective series with a short follow-up, a limited number of
      prospective studies with some methodological pitfalls and a single published
      randomised trial. This review focuses on the current therapeutic approaches, most
      commonly used drugs, role of intrathecal chemotherapy, and indications for
      consolidation radiotherapy, providing recommendations for ordinary clinical
      practice. Some important therapeutic issues, such as the management of meningeal
      and intraocular lymphomas, as well as the relevance of salvage therapy as a
      playground for evaluation of new drugs are also analysed. Finally, the main open
      questions, as well as current and expected investigation trends are discussed.

PMID- 14732887
TI  - Guidelines for the treatment of malignant gliomas in elderly patients.
AB  - More than 80% of intracranial tumours in the elderly are malignant gliomas with
      aggressive behaviour. Older patients have been frequently excluded from clinical
      trials in view of their dismal prognosis and low tolerability of chemo
      radiotherapy treatments, therefore they were underrepresented in the past
      oncological literature. Controversies in the use and dose of RT and in the
      administration of chemotherapeutic agents have not been solved by the small
      retrospective studies conducted so far. It appears reasonable that an aggressive
      treatment with surgery, full dose RT and, possibly, chemotherapy should be
      applied to patients with good performance status, preserved cognitive functions
      and no relevant comorbidities, although in the absence of randomised studies the
      balance of benefits and side effects of integrated treatments remains
      controversial. Patients with low performance status and/or serious comorbidities,
      unable to undergo surgery, may receive a shorter RT plan, or even no treatment at
      all, in consideration of the rapid course of their disease which may be shorter
      than the hypothetical benefit of any specific treatment. Further studies should
      be designed to perform a reliable analysis of prognostic factors of malignant
      gliomas in the elderly in order to tailor treatments to each patient to obtain
      the best feasible benefit without compromising their quality of life.

PMID- 14732888
TI  - New drugs and combinations for malignant glioma.
AB  - A new chemotherapy agent and a method for local delivery of carmustine have
      recently been approved for the treatment of malignant glioma. However, the
      increase in survival remains modest at best with only a very select patients
      currently benefiting truly of these treatments. Combination regimen of different
      alkylating agents or prior O6-alkyltransferase depletion by O6-benzylguanine or
      continuous temozolomide administration schedules have shown some indication for
      increased activity. There is preclinical rational for combining temozolomide with
      radiotherapy and the initial results of a phase II clinical trial were promising.
      Several new cytotoxic agents are currently in clinical trials in patients with
      recurrent glioma. More importantly, targeted therapy and antiangiogenic agents
      have entered the clinical development phase also for patients with glioblastoma
      and anaplastic astrocytoma. The optimal timing of administration of non-cytotoxic
      substances and their integration into the currently available treatments remains
      a challenge. Novel study designs and identification of surrogate markers are
      necessary in order to make rapid and clinically meaningful progress. This review
      summarises the currently available evidence of activity of the recently approved
      drugs against malignant glioma and mentions also agents which have failed to
      demonstrate a significant antitumour activity. Study endpoints are critically
      discussed. Combination regimens with other agents and radiation therapy are
      reviewed. The rational for using antiangiogenic drugs in selected ongoing trials
      is discussed.

PMID- 14732889
TI  - Guidelines to the treatment of meningioma.
AB  - EPIDEMIOLOGY: Meningiomas constitute the largest subgroup of all intracranial
      tumours. Their incidence is about 2-3/100,000/yr, with a 3:2 to 2:1 female:male
      ratio, with a peak incidence in the sixth and the seventh decade of life.
      Meningiomas are usually slow growing, benign neoplasms, causing symptoms by
      compression of adjacent structures or by increased cranial pressure, the specific
      symptoms depending on the location of the tumour. RISK FACTORS: Meningiomas can
      be induced by radiation to the head, even by low dose radiation as used for
      dental radiographic examination after up to 35 yrs interval. The female
      preponderance in meningioma patients as well as the expression of progesterone
      receptor on the cell membranes of more than 50% of meningiomas is argument for an
      influence of gestagene in meningioma proliferation. The most frequent genetic
      predisposition of meningiomas is associated with neurofibromatosis 2 (NF-2); at
      least 40% of meningiomas show a deletion in the NF-2 gene. TREATMENT: To date,
      surgical resection is the mainstay of meningioma therapy. The completeness of the
      resection is the single most important prognostic factor for recurrence. In case
      of incomplete resection or recurrence, radiation therapy with 54 Gy (1.8 to 2
      Gy/fraction) yields comparable results to total resection. Radiosurgery is a
      valuable alternative to radiotherapy (RT), maybe in the future also for surgery,
      as recently demonstrated. In the rare meningioma patients, that have exhausted
      the possibilities of surgery and RT, there have been some successful small series
      using hydroxyurea or interferon alpha. Future therapeutic options might consist
      in octreotide isotopic therapy or targeted therapy directed against tumour neo
      angiogenesis or other proliferation associated markers in meningiomas.

PMID- 14732890
TI  - Guidelines for the treatment of adult intra-cranial grade II-III ependymal
      tumours.
AB  - Intra-cranial ependymal tumours are very rare in the adult population, so most of
      reported series are retrospective, include also paediatric patients and have
      limited statistical power due to the small number of cases. As a consequence,
      universally accepted prognostic factors and therapeutic guidelines are lacking.
      The addition of postoperative chemotherapy with lomustine, vincristine and
      prednisone to cranio-spinal irradiation did not improve survival with respect to
      RT alone in a randomised phase III trial of children with infratentorial
      ependymoma. Different chemotherapy regimens have been tested in children with
      ependymoma or anaplastic ependymoma yielding comparable results to those reported
      for patients receiving RT alone. No data is available for adult population. Thus
      far, there is no proof that the addition of chemotherapy to RT improves the
      outcome and adjuvant chemotherapy should be confined to investigational
      controlled clinical trials.

PMID- 14732891
TI  - Current and future strategies in the management of medulloblastoma in adults.
AB  - Medulloblastoma in adults are rare and differ from their childhood counterparts
      in terms of tumor site (hemispheric location), histological subtype (desmoplastic
      variant), lower incidence of metastatic spread and frequent late relapses. As in
      children the presence of metastatic disease is of major prognostic significance.
      The role of different histological subtypes and molecular genetic/biological
      markers is unknown and deserves further investigations. The therapeutic
      strategies are essentially based on experiences in childhood medulloblastomas.
      Surgery followed by irradiation of the entire central nervous system followed by
      a boost to the posterior fossa is the cornerstones of treatment. A sufficient
      dose prescription and a high quality of treatment are a prerequisite for an
      optimal tumor control. Unlike in children the role of chemotherapy is an open
      question and requires prospective investigations. The forthcoming EORTC-study is
      addressing this issue.

PMID- 14732892
TI  - [Diabetes mellitus in cystic fibrosis].

PMID- 14732893
TI  - [Control of tuberculosis in Germany is still a challenge].

PMID- 14732894
TI  - [Remarkable restricted tuberculosis epidemics in 2001/2002 in two Bavarian
      regions].
AB  - Even if the incidence is further decreasing, tuberculosis must not be
      underestimated in Germany. In 2001, the public health service revealed four
      noteworthy molecular-biologically substantiated tuberculosis infection chains in
      Upper Bavaria and Upper Palatinate. An alcohol-addict frequenting the table
      reserved for regulars in an inn located in the district of E. was the origin for
      a small epidemic with seven tuberculosis cases, whereof six were contagious. In
      the district of D., a manager causes two illnesses at the workplace, and one
      tuberculosis case as well as two tuberculin conversions after visiting a skiing
      hut. An external cleaning lady, who had not been examined previously, causes
      tuberculosis in a three-year old girl in a rehabilitation clinic in the Upper
      Bavarian district of BT. The cavernous pulmonary tuberculosis, which was not
      examined for a long period of time in a nursery-school teacher, caused
      tuberculosis in a three-year-old girl and tuberculin conversion in thirty-four
      children in the Upper Palatinate region.

PMID- 14732895
TI  - [Spread of a drug-resistant strain of mycobacterium tuberculosis among homeless
      people in a German city].
AB  - BACKGROUND: Cases of active pulmonary tuberculosis are much more common among
      homeless people because of their personal risk factors than in the average
      population; it is assumed that there are about 500 000 homeless people in the
      Federal Republic of Germany. Several sputum samples were sent from the
      tuberculosis advice center of the public health office in Hannover to the
      governmental institute of public health services of Lower Saxony in fall 1996 in
      order to carry out laboratory tests for mycobacteria. The isolates found revealed
      an unusual pattern of drug resistance to streptomycin and rifampin. METHODS: The
      sputum samples were tested according to the usual standard test procedures as
      described in DIN 58 943-3 (DIN standard of the German Institute for
      Standardization) and in MiQ 5/1998 (Quality standards in microbiology
      infectiologic diagnostics issued by the German Society for Hygiene and
      Microbiology [DGHM]. DNA-fingerprinting was carried out by the IS 6110-RFLP
      technique. PATIENTS: In Hannover a total of 12 patients with an active pulmonary
      tuberculosis, whose M. tuberculosis-strains showed resistance to streptomycin and
      rifampin, were investigated. 9 of the 12 patients were homeless and lodged in a
      homeless shelter of the city; in one case a healthcare worker acquired a
      tuberculosis infection while caring for these patients. RESULTS: The identity of
      the 12 isolated mycobacteria strains could be proved by IS 6110-fingerprinting.
      The result clearly indicates the existence of a tuberculosis cluster among the
      homeless people in a German city. The treatment of the homeless persons proved to
      be difficult because of the lack of compliance; in 4 cases compulsory isolation
      with therapy in a closed clinic was unavoidable and beforehand 2 of the patients
      even had to be tracked down by the police. CONCLUSIONS: The German law on the
      prevention of infectious diseases offers some new possibilities to the public
      health offices concerning the control and prevention of tuberculosis among
      homeless persons. For example the public health offices are now allowed to run a
      "preventive visiting services" prevention and to practice ambulant therapies; the
      payment of the costs for poor patients is prescribed, too. These possibilities
      should be used in an extended way, as the efforts to control the spread to
      tuberculosis among homeless people need to be intensified.

PMID- 14732896
TI  - [Pleuritis tuberculosa - therapeutic value of repeated chest tapping].
AB  - Tuberculous pleuritis tends to develop fibrosis to a high degree. The use of
      corticosteroids enhances the absorption of pleural effusions, the residual
      pleural thickening, however, remains unaffected. Whether repeated chest tapping
      in patients with persistent effusions in addition to antituberculous therapy
      favourably influences the outcome is not known. Therefore, patients with
      tuberculous pleuritis were examined in a prospective, randomized study. After
      confirmation of the diagnosis patients were randomized in group A with
      antituberculous treatment (Isoniazid, Rifampicin, Pyrazinamid, and Streptomycin)
      alone or in group B with additional pleural tapping for four weeks (phase I). In
      phase II patients in both groups with persistent effusions received oral
      prednisolone (0,75 mg/kg body weight) tapered over four weeks. The extent of
      pleural effusions was determined by chest X-ray. Roentgenological changes were
      evaluated at the end of the observation period. Lung function tests by spirometry
      were performed after two, four, eight weeks, and at the last follow up visit. At
      the end of phase I no pleural effusion could be observed roentgenologically in
      group A in 7 of 16 patients (44 %) and in group B in 10 of 16 patients (63 %) (p
      = n. s.). At the end of phase II extensive residual thickening was observed in
      one patient (group B) necessitating pleurectomy six months later. The lung
      function parameters demonstrated a restrictive pattern, which did not differ
      significantly at the end of the observation period. After a mean follow-up period
      of four months none or minimal residual changes could be observed radiologically
      in the remaining patients. In summary, despite the low number of patients
      examined, this study shows that in patients with tuberculous pleuritis repeated
      chest tapping in addition to antituberculous medication does not seem to benefit
      the patient, as neither the degree of residual pleural thickening nor the
      restrictive lung function impairment seem to be influenced significantly.

PMID- 14732897
TI  - [Adaptive servoventilation: effect on Cheyne-Stokes-Respiration and on quality of
      life].
AB  - BACKGROUND: Adaptive servo-ventilation (ASV) (AutoSetCS, ResMed) is a novel non
      invasive ventilation modality for the treatment of Cheyne-Stokes-Respiration
      (CSR) in patients with heart failure. This study aimed to investigate the effect
      of ASV on sleep disordered breathing (SDB), afternoon nap duration, urine
      voidings, and quality of life. METHODS: 11 patients with CSR due to heart failure
      (EF < 40 %) were treated with ASV for a period of 6 weeks. Apnea-Hypopnoe-Index
      (AHI), Arousalindex (AI), duration of afternoon nap, number of voidings, and
      heart specific quality of life were assessed before and at the end of the
      treatment period. RESULTS: The average usage time of ASV was 5.8 +/- 2.1/h per
      day. With ASV the AHI was reduced from 48.2 +/- 11.6 to 6.4 +/- 8.3/h (p < 0.001)
      and the AI from 33.9 +/- 12.5 to 18.4 +/- 9.3 /h (p < 0.05). The afternoon nap
      duration was significantly less (1.4 +/- 0.6 vs. 0.7 +/- 0.4 hours per day; p =
      0.004) as was the number of nocturnal voidings (2.9 +/- 0.7 vs. 1.1 +/- 0.3 per
      night; p = 0.007). There was a significant improvement in heart specific quality
      of life as measured with the Minnesota Living with heart failure questionnaire
      (43.5 +/- 21.1 vs. 27.6 +/- 15.7 (p = 0.02). CONCLUSION: ASV is well tolerated
      and improves SDB and quality of life of patients with heart failure with CSR.

PMID- 14732898
TI  - [Pulmonary Infiltrate, Pleural Effusion and IgM Macroglobulinaemia].
AB  - We report a 71-year-old mam with known IgM- Macroglobulinemia, who developed
      infiltrative pulmonary changes and a pleural effusion. Both, the pleural effusion
      and bronchoalveolar lavage revealed monoclonal IgM positive B-lymphocytoes.
      Transbronchial biopsies showed tissue infiltrates of lymphoplasmocytic cells,
      consistent with a pleuropulmonary manifestation of Morbus Waldenstroem. Bone
      marrow and gastrointestinal involvement could be excluded, and the diagnosis of a
      primary pulmonary immunocytoma was made. The patient underwent partial lung
      resection with removal of the affected lung tissue. Pleuropulmonary changes in
      patients with IgM-Macroglobulinaemia or Morbus Waldenstroem may be due to
      pulmonary involvement by the hematological disease.

PMID- 14732899
TI  - [Diagnosis and therapy of cystic fibrosis-related diabetes].

PMID- 14732900
TI  - [Improving compliance under psychodynamic aspects].

PMID- 14732901
TI  - [On the history and future of thoracoscopy].

PMID- 14732903
TI  - Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a
      mitochondrial matrix protein.
AB  - Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder
      affecting the brain, gastrointestinal tract, and peripheral vessels. High levels
      of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase
      activity is decreased in skeletal muscle. By use of a combination of homozygosity
      mapping, integration of physical and functional genomic data sets, and mutational
      screening, we identified GenBank D83198 as the gene responsible for EE. We also
      demonstrated that the D83198 protein product is targeted to mitochondria and
      internalized into the matrix after energy-dependent cleavage of a short leader
      peptide. The gene had previously been known as "HSCO" (for hepatoma subtracted
      clone one). However, given its role in EE, the name of the gene has been changed
      to "ETHE1." The severe consequences of its malfunctioning indicate an important
      role of the ETHE1 gene product in mitochondrial homeostasis and energy
      metabolism.

PMID- 14732904
TI  - Inherent bias toward the null hypothesis in conventional multipoint nonparametric
      linkage analysis.
AB  - Traditional nonparametric "multipoint" statistical procedures have been developed
      for assigning allele-sharing values at a locus of interest to pairs of relatives
      for linkage studies. These procedures attempt to accommodate a lack of
      informativity, nongenotyped loci, missing data, and related issues concerning the
      genetic markers used in a linkage study. However, such procedures often cannot
      overcome these phenomena in compelling ways and, as a result, assign relevant
      relative pairs allele-sharing values that are "expected" for those pairs. The
      practice of assigning expected allele-sharing values to relative pairs in the
      face of a lack of explicit allele-transmission information can bias traditional
      nonparametric linkage test statistics toward the null hypothesis of no locus
      effect. This bias is due to the use of expected values, rather than to a lack of
      information about actual allele sharing at relevant marker loci. The bias will
      vary from study to study on the basis of the DNA markers, sample size, relative
      pair types, and pedigree structures used, but it can be extremely pronounced and
      could contribute to a lack of consistent success in the application of
      traditional nonparametric linkage analyses to complex human traits and diseases.
      There are several potential ways to overcome this problem, but their foundations
      deserve greater research. We expose many of the issues concerning allele sharing
      with data from a large affected-sibling-pair study investigating the genetic
      basis of autism.

PMID- 14732905
TI  - Premature myocardial infarction novel susceptibility locus on chromosome 1P34-36
      identified by genomewide linkage analysis.
AB  - The most frequent causes of death and disability in the Western world are
      atherosclerotic coronary artery disease (CAD) and acute myocardial infarction
      (MI). This common disease is thought to have a polygenic basis with a complex
      interaction with environmental factors. Here, we report results of a genomewide
      search for susceptibility genes for MI in a well-characterized U.S. cohort
      consisting of 1,613 individuals in 428 multiplex families with familial premature
      CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4+/-9.7
      years. Genotyping was performed at the National Heart, Lung, and Blood Institute
      Mammalian Genotyping Facility through use of 408 markers that span the entire
      human genome every 10 cM. Linkage analysis was performed with the modified
      Haseman-Elston regression model through use of the SIBPAL program. Three
      genomewide scans were conducted: single-point, multipoint, and multipoint
      performed on of white pedigrees only (92% of the cohort). One novel significant
      susceptibility locus was detected for MI on chromosomal region 1p34-36, with a
      multipoint allele-sharing P value of <10(-12) (LOD=11.68). Validation by use of a
      permutation test yielded a pointwise empirical P value of.00011 at this locus,
      which corresponds to a genomewide significance of P<.05. For the less restrictive
      phenotype of CAD, no genetic locus was detected, suggesting that CAD and MI may
      not share all susceptibility genes. The present study thus identifies a novel
      genetic-susceptibility locus for MI and provides a framework for the ultimate
      cloning of a gene for the complex disease MI.

PMID- 14732907
TI  - [GIN's activity in the past five years].
AB  - This letter summarises the main activities of the journal during the last five
      years. The quality of the journal has been improved and it is now included in the
      Library of Medicine in Bethesda. Moreover, the journal is listed in the Index
      Medicus and its articles appear in Medline. I believe that the new Editor-in
      chief, Francesca Mallamaci, with her enthusiasm will continue to improve the
      journal.

PMID- 14732908
TI  - [Neoangiogenesis: from molecular biology to clinical medicine].
AB  - Cardiovascular disease is the most common cause of premature death in patients
      with end-stage renal disease, probably due to a specific "uraemic cardiomyopathy"
      This article reviews the pathogenesis of cardiac changes in uraemia and
      particularly the role of an impaired vessel formation. Experimental and autoptic
      data showed remarkable changes in heart capillarization in renal failure, i.e. a
      decrease in myocardial capillary supply and a concomitant increase in
      intercapillary distance. Promoting the formation of new collateral vessels in
      ischemic tissues using angiogenic growth factors (therapeutic angiogenesis), such
      as VEGF, constitutes a promising approach for the treatment of uraemic
      cardiomyopathy.

PMID- 14732906
TI  - Joint analysis of the DRD5 marker concludes association with attention
      deficit/hyperactivity disorder confined to the predominantly inattentive and
      combined subtypes.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable,
      heterogeneous disorder of early onset, consisting of a triad of symptoms:
      inattention, hyperactivity, and impulsivity. The disorder has a significant
      genetic component, and theories of etiology include abnormalities in the
      dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major
      susceptibility genes. An initial report of association between ADHD and the
      common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5
      gene has been followed by several studies showing nonsignificant trends toward
      association with the same allele. To establish the postulated association of the
      (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent
      samples of probands and their parents, analyzed them individually and, in the
      absence of heterogeneity, analyzed them as a joint sample. The joint analysis
      showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence
      interval 1.12-1.38). This association appears to be confined to the predominantly
      inattentive and combined clinical subtypes.

PMID- 14732909
TI  - [Dent's disease: hereditary nephrolithiasis related to defective tubular
      endocytosis processes].
AB  - Dent's disease, a X-linked hypercalciuric nephrolithiasis, is caused by mutations
      of the CLCN5 gene. The disease is characterised by low molecular weight
      proteinuria with variable presence of hypercalciuria, hyperphosphaturia,
      nephrocalcinosis, and kidney stones. CLCN5 encodes a chloride channel belonging
      to the voltage-gated chloride channel family, which is predominantly expressed in
      the endosomes of proximal tubular cells. By shunting the current of electrogenic
      H+-ATPase, ClC-5 is crucial for efficient acidification of renal endosomes. As
      shown in knock-out mouse models, the ClC-5 loss of function causes severe
      impairment of receptor-mediated endocytosis, as well as the endocytotic retrieval
      of plasma membrane proteins including megalin. In a minority of patients with
      classical Dent's disease, the analysis of CLCN5 coding sequences failed to
      identify causative mutations. It is conceivable that mutations in the 5' upstream
      regulatory regions could impair the correct processing and translation of CLCN5.
      The complexity of its promoter region seems to support this hypothesis. Molecular
      diagnosis of Dent's disease is now available; since the risk of developing renal
      insufficiency in adult life is elevated for this type of nephrolithiasis, the
      correct diagnosis could potentially modify the natural history of the disease by
      preventing the evolution towards uraemia.

PMID- 14732910
TI  - [Oscillometric wrist devices: comparison with the standard mercury
      sphygmomanometer and estimate of the "supine" error].
AB  - Before introducing a wrist device (NAIS-Matsushita) for blood pressure (BP)
      measurement in our Unit, we formally tested its validity. Since the wrist
      position is critical and BP in the clinical setting is often measured with
      patients lying in bed, we also estimated the error introduced by allowing the
      wrist to lay flat at the bed level. Ten normal subjects and 20 hypertensive
      patients took part in two consecutive studies. In the first study the subjects
      were sitting and the blood pressure was simultaneously taken with the
      auscultatory mercury sphygmomanometer on the left arm and with the NAIS on the
      right wrist. The wrist was kept at the heart level. In the second study two NAIS
      devices were used with the subjects lying in bed; the left wrist was allowed to
      stay at the bed level, while the right one was kept at the heart level. The
      diastolic BP was consistently underestimated (P< 0.001) by the wrist device (79
      mmHg 95%CI: 75-83) as compared to the values obtained with the standard mercury
      sphygmomanometer (85 CI: 79-88). No significant difference was found in systolic
      BP (mercury: 135 CI: 127-143; wrist 134 CI: 126-141). In the second study the BP
      (systolic and diastolic) was markedly higher (P<0.001) when the wrist was kept at
      the bed level (systolic bed level: 144 CI: 135-152; systolic heart level: 135
      CI:126-141; diastolic bed level: 83 CI:78-88; diastolic heart level: 76 CI:71
      79).

PMID- 14732911
TI  - [Daily nutrient intake in hemodialysis].
AB  - BACKGROUND: Although there is a higher nutrient requirement, food intake in
      haemodialysis patients is often inadequate. Protein nitrogen appearance (PNA)
      indirectly estimates the mean protein intake during the short interdialysis
      period, but it does not measure the daily nutrient intake, which is generally
      unknown. We carried out a longitudinal study aimed at estimating the daily
      nutrient intake and its relationship with the nutritional status of haemodialysis
      patients. METHODS: We selected 28 haemodialysis patients with adequate
      nutritional status and no evidence of risk-factor for malnutrition. Patients were
      treated with biocompatible membranes, low-flux and high bicarbonate dialysis,
      Kt/V > 1.2, PNA > 1.1 g/kg/day and erythropoietin. We measured every four months
      daily PNA, protein and calorie intake (DPI, DCI) as well as weight gain (WG)
      during an entire week for one-year. The nutritional status was assessed by
      biochemical and BIA markers. RESULTS: Twenty seven subjects (8 F, 19 M; age 57.1
      +- 2.7 yeas; dialysis age 105 +- 13 months) completed the trial. The mean
      interdialytic PNA did not change in both long- and short-interdialysis periods,
      resulting in the "normal" range (> 1.1 g/kg/day); however, daily levels of
      protein and calorie intake were significantly reduced on the third day during the
      long interdialysis interval. Eight patients showed time-averaged values of DPI
      and DCI lower than 0.8 g/kg/day and 25 Kcal/kg/day, respectively, on the third
      day (LOW group), values that were associated with similar changes in WG. Such a
      highly reduced nutrient intake during the third interdialysis day was associated
      with a normal PNA value (1.23 +- 0.05 g/kg/day vs 1.30 +- 0.06 in CON, NS) when
      measured during the short interdialysis period (S), just as it is in clinical
      practice; in contrast, when the PNA value was measured during the long
      interdialysis period it was found to be significantly reduced (1.07 +- 0.08
      g/kg/day vs 1.37 +- 0.06 in CON, p < 0.05 and vs S, p < 0.05). During the study,
      the body weight progressively decreased from 68.0 +- 5.5 to 65.8 +- 5.9 kg (p <
      0.05) in the LOW group, due to the decrease in lean body mass, as suggested by
      the reduction in serum creatinine (9.2 +- 1.1 vs 8.1 +- 0.7 mg/dL, p < 0.05),
      creatinine generation (835 +- 155 vs 723 +- 106 mg/die, p < 0.05) and serum
      albumin (3.96 +- 0.07 vs 3.66 +- 0.06 g/dL, p < 0.05). Moreover, reactance and
      phase angle declined in the LOW group (from 54 +- 4 to 44 +- 3 ohms, p < 0.05 and
      5.5 +- 0.3 to 4.5 +- 0.3 degrees, p < 0.05, respectively). At the end of the
      study the nutritional status in the LOW group was reduced as compared to the CON
      group. CONCLUSIONS: In stable, well-nourished haemodialysis patients, in absence
      of known risk factors for malnutrition, the daily nutrient intake is variable and
      progressively reduce during the interdialytic interval. The measurement of
      interdialytic PNA, as is done in clinical practice, does not enable the discovery
      of such abnormal eating behaviour; the low daily nutrient intake, on the
      contrary, can be evidenced by the daily measurement of either PNA or weight gain,
      and it can also be inferred by the reduced PNA during the long interdialytic
      period. Finally, the persistent reduction in nutrient intake below the threshold
      of 0.8 g/kg/day of proteins and 25 Kcal/kg/day one day a week, is capable of
      inducing body protein wasting and moderate impairment of the nutritional status.

PMID- 14732912
TI  - [Double renal transplant. Retrospective analysis of data on the patient
      population with double kidney transplantation in the setting of the AIRT].
AB  - BACKGROUND: The number of patients on the waiting list for renal transplantation
      has progressively increased in the last decade, while the number of potential
      donors have remained the same. The expansion of the donor pool using marginal
      donors may represent a possible, although partial solution to this problem. Thus,
      the aim of the present analysis was to evaluate the graft survival of double
      renal transplant from marginal donors performed within the Associazione
      InterRegionale Trapianti (AIRT) and to assess whether this procedure is
      characterized by an increase in surgical complications. PATIENTS: 79 double renal
      transplants were performed from January 1st 1999 to December 31st 2002 in three
      AIRT transplant centers (Bari, Bologna, Torino). Immunosuppressive therapy for
      all patients included anti-IL-2 receptor antibodies, corticosteroids, tacrolimus
      and mofetil micophenolate. RESULTS: Graft survival was 90% at 36 months. Acute
      rejection incidence was 6.4%, while the incidence of surgical complications was
      16.6%. CONCLUSIONS: The present study opens new perspectives to overcome the
      actual shortage of donor kidneys. Indeed, the use of marginal organs for double
      renal transplantation not suitable for single transplantation may create an
      additional pool of potential donors and significantly increase the number of
      kidney transplants.

PMID- 14732913
TI  - [HCV+ patients on the waiting list for kidney transplantation. Retrospective
      analysis of data on the patient population with hepatitis C on the waiting list
      for kidney transplantation in the setting of the AIRT].
AB  - BACKGROUND: HCV infection in hemodialysis is still a matter of debate from an
      epidemiological and clinical point of view. Evaluation criteria for HCV-infected
      patients as transplant candidates are still not adequately standardized. Aims of
      the present study were to investigate: 1. the percentage of HCV positive patients
      on the waiting list of three Italian regions belonging to the Associazione
      InterRegionale Trapianti (AIRT); 2. to analyze the clinical approach in the
      evaluation of these patients in the attempt to define national guidelines for
      their pre- and post-transplant management. PATIENTS: We evaluated 2045 uremic
      patients on the waiting lists of four transplant centers (Bari, Bologna, Modena,
      Novara) belonging to AIRT at 31/12/2002. RESULTS: The overall prevalence of HCV
      positive patients was 14.2%, with a peak in the Puglia waiting list. The most
      common screening tests were AST and ALT serum levels and viral load (HCV RNA).
      Although there is a clear evidence that histological parameters are the main
      diagnostic and prognostic markers, a liver biopsy was performed in only 9.5% of
      patients. An even smaller percentage of HCV-infected patients underwent anti
      viral therapy. CONCLUSIONS: Our retrospective analysis evidenced the need to
      improve common clinical strategies in approaching HCV-infected canditates to
      renal transplantation in the attempt to improve their post-transplant outcome.

PMID- 14732914
TI  - [Malignant neoplasia and kidney transplantation. Retrospective analysis of data
      on the population having kidney transplantation with de novo neoplasia in the
      setting of the AIRT].
AB  - BACKGROUND: In transplanted patients undergoing immunossuppressive therapy the
      incidence of malignant neoplasia is 3-4 times higher than in the general
      population. Aim of the present study was to evaluate the prevalence of different
      tumours and the links between modulation of immunosuppressive therapy and patient
      and graft survival. PATIENTS: We evaluated 2029 kidney-transplanted patients from
      four Transplant Centres (Bari, Bologna, Modena, Novara) belonging to the
      Associazione InterRegionale Trapianti (AIRT). RESULTS: The incidence of
      neoplastic disease after transplantation was 3.9% in our population with a median
      time between transplantation and clinical onset of 23 months. We demonstrated a
      significant difference in the geographical distribution of different tumours. We
      did not observe any correlation with specific immunosuppressive drugs. Finally,
      dramatic reduction of the immunosuppression levels did not modify either the
      patients' or the graft's survival. CONCLUSIONS: Several factors can influence the
      post-transplant onset of neoplastic diseases with immunosuppressive therapy
      playing a pivotal role. The implementation of a National Registry would be the
      first step in an attempt to optimise immunosuppression in this particular group
      of patient's.

PMID- 14732915
TI  - [Critical appraisal of systematic reviews of randomised trials in nephrology:
      theory and practice for interpreting level I evidence].
AB  - INTRODUCTION: Systematic reviews represent the primary level of evidence (level I
      evidence) and an excellent answer to causality questions. They should be based
      upon high quality standards and the critical appraisal of such study design is
      fundamental. METHODS: In this review we introduce the primary indicators of
      quality and guide our readers through the process of critical appraisal of
      systematic reviews. RESULTS: The main criteria in critically appraising
      systematic reviews in nephrology are the adequate presentation of a research
      question, adequate selection of studies, comprehensiveness of search strategies,
      the quality assessment of included studies, the fact that all procedures have
      been performed independently by at least 2 investigators, the exploration of
      heterogeneity, the type of results and their applicability. In nephrology we
      still lack a large number of systematic reviews because of the lack of randomised
      trials. CONCLUSIONS: Preparing a large number of systematic reviews is an
      important challenge for the nephrology community. This community should prepare
      more randomised trials to answer intervention questions and should make an effort
      to synthesise the evidence in the form of systematic reviews. It is essential
      that available systematic reviews be critically appraised and their results
      implemented in the clinical practice whenever they are based on high
      methodological standards.

PMID- 14732916
TI  - [Historical Archives of Italian Nephrology. Diabetic nephropathy and insulin
      discovery: two parallel histories].
AB  - In 1936, Kimmelstiel and Wilson described the nodular glomerulosclerosis in
      patients with diabetes mellitus on insulin treatment. The nodular
      glomerulosclerosis is referred to as diabetic nephropathy. Fifteen years earlier
      insulin was discovered. This discovery at the University of Toronto (Canada) in
      1921-22 by Banting, Macleod, Best and Collip was one of the most dramatic events
      in the history of the treatment of the disease. The impact of insulin was so
      sensational because of the incredible effect it had on diabetic patients. Those
      who first watched starved, sometimes comatose, diabetics receive insulin and
      return to life witnessed one of the genuine miracles of modern medicine. The
      discovery has became the "elixir of life" for millions of human beings around the
      world. Insulin had not emerged out of a vacuum but was the culmination of years
      of work by dozens of scientists in many countries. The Canadian scientists were
      the first to succeed in isolating insulin. Their work, however, was accurately
      constructed to confirm the ideas of earlier researchers, such as Murray,
      Paulesco, Allen, Minkowski, Derwitt, Zuelzer. These men, in addition to Banting,
      Macleod, Best and Collip, knew they were making medical history but
      paradoxically, with their "elixir of life" they allowed some complications of
      diabetes to emerge. Diabetic nephropathy was one of them. The struggle of the
      "Toronto quartet" for credit was inspired by man's desire to have a place in
      history, to have a sort of immortality open to him, an aspiration that is
      certainly legitimate. But perhaps the Canadian group misjudged both their
      situation and posterity's point of view. They probably failed to consider the
      unintentional effect of insulin treatment: diabetic nephropathy as a consequence
      of adding years to a diabetic's life.

PMID- 14732917
TI  - [Chronic inflammation and cardiovascular risk in hemodialysis].
AB  - Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in
      patients with end-stage renal disease (ESRD). Traditional risk factors are common
      in ESRD patients, but they alone may not be sufficient to account for the high
      prevalence of CVD in this population. Recent clinical evidence demonstrates that
      chronic inflammation, a non traditional risk factor which is commonly observed in
      ESRD patients, may be associated with the presence of poor nutritional parameters
      and progressive atherosclerotic CVD. Based on these observations, the presence in
      ESRD patients of a syndrome consisting in malnutrition, signs of systemic chronic
      inflammation and atherosclerosis (MIA syndrome) has recently been suggested. A
      central role in this syndrome is played by the proinflammatory cytokines
      generated in response to factors such as chronic renal failure and infectious
      inflammatory co-morbid disease. It is now clear that the immune response, both
      innate and adaptive, is the main cause of inflammation characterising
      atherosclerosis. As there is as yet no recognized, or even proposed, treatment
      for ESRD patients with chronic inflammation, it would be of obvious interest to
      study the long-term effect of various inflammatory treatment strategies on the
      nutritional and cardiovascular status as well as the outcome in these patients.

PMID- 14732918
TI  - [Focal segmental glomerulosclerosis with IgA deposits in a patient with
      ulcerative colitis].
AB  - BACKGROUND: Glomerular diseases are described in patients with active ulcerative
      colitis (UC). Likely drug-induced interstitial nephritis, and nephrotic syndrome
      due to minimal change disease, have been reported in a few patients with UC on
      treatment with mesalazine and sulfasalazine (5-ASA). We describe a 33 year-old
      patient with a 5-years history of UC who recently developed nephrotic syndrome
      associated with microscopic haematuria. Blood pressure and renal function were
      normal. The patient was on azathioprine (AZA), mesalazine and sulfasalazine
      during the last year for his colitis, with good control of bowel disease. Renal
      biopsy revealed a focal segmental glomerulosclerosis (FSGS) associated with
      mesangial IgA deposits; no signs of interstitial nephritis were found. 5-ASA was
      discontinued, AZA was reduced and a rapid remission of the nephrotic syndrome was
      observed after 6 weeks of steroid therapy (1 mg/kg/day per os) associated with
      ramipril 5 mg/day, with a follow-up of 9 months. CONCLUSIONS: To our knowledge
      this is the first report of UC and GSFS associated with IgA deposits. The
      occurrence of nephrotic syndrome during UC is suggestive of an association
      between UC and FSGS, but a possible role of mesalazine and /or sulfasalazine in
      its pathogenesis cannot be excluded. Mesangial IgA deposits could be an
      "occasional" further occurrence, considering the chronic inflammation of colonic
      mucosa and the altered immune response of patients with UC.

PMID- 14732919
TI  - Loss of a small region around the PTEN locus is a major chromosome 10 alteration
      in prostate cancer xenografts and cell lines.
AB  - We examined 11 prostate cancer xenografts and 4 cell lines for chromosome 10
      alterations. Conventional comparative genomic hybridization (CGH) and array-based
      CGH revealed a pattern of loss of distal 10p, gain of proximal 10p and 10q, and
      loss of distal 10q. In addition, array CGH identified 2 high-level amplifications
      in the cell line PC3, homozygous deletions of PTEN in PC3 and in the xenografts
      PCEW, PC133, and PC324, and small single- or double-copy deletions around PTEN in
      PCEW, PC82, PC324, PC346, and LNCaP. Allelotype analysis confirmed all 10p
      losses, 5 of 6 large 10q losses, the homozygous deletions, and the small regions
      of one copy loss. MXI1, DMBT1, and KLF6 were excluded as important tumor
      suppressor genes. The sizes of homozygous deletions around PTEN ranged from 1.2
      Mbp (PC133) to <30 kbp (PTEN exon 5 in PC295). The regions of small single- or
      double-copy loss around PTEN were all less than 4.5 Mbp. The loss of 1 or 2
      copies of PTEN was always accompanied by loss of the distal flanking gene
      FLJ11218 and, in most cases, by loss of the proximal flanking genes MINPP1,
      PAPSS2, and FLJ14600. Furthermore, differential expression was detected for
      FLJ11218 and PAPSS2. Complete deletion or inactivating mutation of PAPSS2 was
      found in at least 3 samples. In addition to 4 homozygous deletions, 1 missense
      mutation was detected in FLJ11218. In conclusion, our data provide evidence that
      loss of a small region around PTEN is the major chromosome 10 alteration in
      prostate cancer xenografts and cell lines. In some of the samples, PTEN
      inactivation was accompanied by loss of 1 MINPP1 allele, loss of 1 copy,
      mutation, or low expression of PAPSS2, and most frequently by loss of 1 or 2
      copies or low expression of FLJ11218.

PMID- 14732920
TI  - Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast
      carcinogenesis.
AB  - Deleted in malignant brain tumors 1 (DMBT1) has been proposed as a candidate
      tumor suppressor for brain and epithelial cancer. Initial studies suggested loss
      of expression rather than mutation as the predominant mode of DMBT1 inactivation.
      However, in situ studies in lung cancer demonstrated highly sophisticated changes
      of DMBT1 expression and localization, pointing to a chronological order of
      events. Here we report on the investigation of DMBT1 in breast cancer in order to
      test whether these principles might also be attributable to other tumor types.
      Comprehensive mutational analyses did not uncover unambiguous inactivating DMBT1
      mutations in breast cancer. Expression analyses in the human and mouse mammary
      glands pointed to the necessity of DMBT1 induction. While age-dependent and
      hormonal effects could be ruled out, 9 of 10 mice showed induction of Dmbt1
      expression after administration of the carcinogen 7,12
      dimethybenz(alpha)anthracene prior to the onset of tumorigenesis or other
      histopathological changes. DMBT1 displayed significant up-regulation in human
      tumor-flanking tissues compared to in normal breast tissues (P < 0.05). However,
      the breast tumor cells displayed a switch from lumenal secretion to secretion to
      the extracellular matrix and a significant down-regulation compared to that in
      matched normal flanking tissues (P < 0.01). We concluded that loss of expression
      also is the predominant mode of DMBT1 inactivation in breast cancer. The dynamic
      behavior of DMBT1 in lung carcinoma is fully reflected in breast cancer, which
      suggests that this behavior might be common to tumor types arising from
      monolayered epithelia.

PMID- 14732921
TI  - Identification of cytogenetic subgroups and karyotypic pathways of clonal
      evolution in follicular lymphomas.
AB  - Follicular lymphoma (FL) is characterized by the activation of BCL2 through
      t(14;18)(q32;q21). Additional acquired mutations are necessary to generate a
      fully malignant clonal proliferation. Many of these secondary genetic alterations
      are visible in the clonal karyotype; however, the sequence by which they arise
      and their influence on clinical behavior have not been determined. The ability to
      address these issues has been hampered by the lack of computational methods to
      manipulate complex chromosomal data in a sufficiently large cohort of cases. In
      the present investigation, we analyzed secondary karyotypic alterations in 336
      cases of FL with t(14;18) to identify the most common regions of recurrent
      chromosomal gain or loss. This revealed 29 recurrent changes present in more than
      5% of the tumors. Each tumor karyotype was then assessed for the presence or
      absence of each of these 29 specific changes. By statistical means, we show that
      the chromosomal changes arise in an apparent temporal order, with distinct early
      and late changes. We identify, by principal-components analysis, four possible
      cytogenetic pathways that characterize the early stages of clonal evolution,
      which converge to a common route at later stages. We show that FLs with t(14;18)
      may be classified into cytogenetic subgroups determined by the presence or
      absence of 6q-, +7, or der(18)t(14;18). Correlation with clinical outcomes in a
      subset of cases with clinical data revealed del(17p) and +12 to be correlated
      with an adverse clinical outcome. The clinical implications of these pathways of
      clonal evolution need to be examined on a prospective basis in a large cohort of
      FLs.

PMID- 14732922
TI  - High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a
      high-risk Chinese population.
AB  - Because previous studies have shown that loss of heterozygosity (LOH) is common
      on chromosome arm 9p in esophageal squamous cell carcinoma (ESCC) and that
      genetic alterations in CDKN2A and CDKN2B on 9p are also common, we sought to
      determine whether LOH and these genetic alterations are related. We performed LOH
      studies on chromosome bands 9p21-p22 and searched for genetic alterations of
      CDKN2A and CDKN2B in 56 ESCCs from a high-risk Chinese population. Seventy-three
      percent of patients were found to have LOH at one or more loci on chromosome
      bands 9p21-p22, and LOH occurred more frequently in patients with a family
      history of upper gastrointestinal cancer than in those with a negative family
      history (P = 0.01, global permutation test). CDKN2A mutations (point mutations,
      deletions, insertions) were observed in 25% (14 of 56) of cases, and the LOH
      pattern was significantly different for individuals with and without a CDKN2A
      mutation (P = 0.01, global test). Three new single nucleotide polymorphisms
      (SNPs) and 2 previously reported SNPs were identified in this group of patients.
      Intragenic allelic loss at polymorphic sites in CDKN2A was detected in 32% (18 of
      56) of patients. Seven of the 56 (13%) cases exhibited what is considered classic
      evidence (n = 4) or showed potential evidence (n = 3) of biallelic inactivation.
      Only one alteration was observed in CDKN2B, G171A in the 5' untranslated region.
      Both mutation and intragenic allelic loss in CDKN2A appear to play a role in the
      development of ESCC.

PMID- 14732923
TI  - RAS, FLT3, and TP53 mutations in therapy-related myeloid malignancies with
      abnormalities of chromosomes 5 and 7.
AB  - Oncogenic mutations in the KRAS2, NRAS, or FLT3 gene are detected in more than
      50% of patients with de novo acute myeloid leukemia (AML). RAS mutations are also
      prevalent in de novo myelodysplastic syndrome (MDS), especially chronic
      myelomonocytic leukemia and juvenile myelomonocytic leukemia. However, few
      studies have examined these genetic lesions in therapy-related myeloid
      malignancies. Monosomy 7/del(7q) and monosomy 5/del(5q) represent the most common
      cytogenetic abnormalities in therapy-related MDS and AML (t-MDS/t-AML) and are
      strongly associated with prior exposure to alkylating agents. Mutational analysis
      of bone marrow specimens from a well-characterized cohort of 26 t-MDS/t-AML
      patients with abnormalities of chromosomes 5 and/or 7 revealed 3 with RAS
      mutations. Further analyses of 23 of these cases uncovered one FLT3 internal
      tandem duplication and five TP53 mutations. The four patients with RAS or FLT3
      mutations had monosomy 7, including one with abnormalities of chromosomes 5 and
      7. One specimen demonstrated mutations in both KRAS2 and TP53. RAS and FLT3
      mutations, which are thought to stimulate the proliferation of leukemia cells,
      appear to be less common in t-MDS/t-AML than in de novo AML, whereas TP53
      mutations are more frequent.

PMID- 14732924
TI  - Expression profiling of the influence of RAS mutants on the TGFB1-induced
      phenotype of the pancreatic cancer cell line PANC-1.
AB  - Expression profiling analyses were used to elucidate the functional relevance of
      RAS proteins in mediating the effect of TGFB1 on the transcriptional phenotype of
      the pancreatic cancer cell line PANC-1. Despite the presence of one mutated KRAS2
      allele in parental PANC-1 pancreatic cancer cells, RAS-dependent signal
      transduction remained susceptible to stimulation by EGF and TGFB1. To analyze the
      impact of RAS proteins on the TGFB1-induced transcriptional phenotype, we used
      PANC-1 cells stably transfected with a dominant negative HRAS(S17N) mutant or
      with a constitutively active KRAS2(G12V) mutant. TGFB1 treatment of mock
      transfected PANC-1 cells led to an expression profile suggestive of epithelial
      mesenchymal transdifferentiation (EMT). Profiling of the HRAS(S17N)-expressing
      clone demonstrated that induction of endogenous RAS activity by TGFB1 is required
      for the development of the TGFB1-induced transcriptional phenotype of PANC-1
      cells. The expression of the KRAS2(G12V) mutant by itself repressed transcription
      of markers of epithelial differentiation and induced transcription of several
      extracellular matrix-associated genes. This effect was not enhanced further by
      TGFB1 treatment. In contrast, transcript levels of genes associated with
      proliferation and cell cycle progression did not appear to be the primary targets
      of the synergism between the RAS- and TGFB1-dependent cascades. The introduction
      of the dominant negative and the constitutively active RAS mutants induced partly
      overlapping and partly inverse effects on the TGFB1-induced expression profile of
      PANC-1 cells. Additional mechanisms such as the induction of autocrine loops and
      the use of different RAS isoforms or alternate, ERK-independent signaling
      pathways may be involved in the interaction between the RAS- and the TGFB1
      dependent signaling cascades.

PMID- 14732925
TI  - Germ-line mutations in BRCA1 or BRCA2 in the normal breast are associated with
      altered expression of estrogen-responsive proteins and the predominance of
      progesterone receptor A.
AB  - The breast cancer susceptibility genes BRCA1 and BRCA2 are responsible for a
      large proportion of familial breast and ovarian cancer, yet little is known of
      how disruptions in the functions of the proteins these genes encode increased
      cancer risk preferentially in hormone-dependent tissue. There is no information
      on whether a germ-line mutation in BRCA1 or BRCA2 causes disruptions in hormone
      signaling pathways in the normal breast. In this study markers of hormone
      responsiveness were measured in prophylactically removed normal breast tissue (n
      = 31) in women bearing a germ-line pathogenic mutation in one of the BRCA genes.
      The estrogen receptor (ER) and proteins associated with ER action in hormone
      sensitive tissues, namely, PS2 and the progesterone receptor (PR), were detected
      immunohistochemically. ER expression was not different in BRCA mutation carriers
      than in noncarriers, but there was a reduction in PS2 expression. PR expression
      was also reduced, and there was a striking lack of expression of the PRB isoform,
      which resulted in cases with PRA-only expression in BRCA1 and BRCA2 mutation
      carriers. The alterations in PS2 and PR expression were similar in the BRCA1 and
      BRCA2 carriers, demonstrating that although these proteins are structurally and
      functionally distinct, there is overlap in their interaction with hormone
      signaling pathways. This study provides evidence for altered cell function
      arising from loss of function of one BRCA allele in the normal breast, leading to
      PS2 loss, preferential PRB loss, and expression of PRA alone. In breast cancer
      development, PRA overexpression becomes evident in premalignant lesions and is
      associated with features of poor prognosis in invasive disease and altered cell
      function in vitro. The results of this study suggest that heterozygosity for a
      germ-line mutation in BRCA1 or BRCA2 results in development of PRA predominance.
      This is likely to lead to changes in progesterone signaling in hormone-dependent
      tissues, which may be a factor in the increased risk of cancer in these tissues
      in women with germ-line BRCA1 or BRCA2 mutations.

PMID- 14732926
TI  - Evaluation of genetic patterns in different tumor areas of intermediate-grade
      prostatic adenocarcinomas by high-resolution genomic array analysis.
AB  - Prostate cancer is known for its highly heterogeneous histological appearance.
      Data concerning the cytogenetic content of areas with different histology are
      sparse. We have genetically evaluated 10 prostatic adenocarcinomas with
      intermediate histopathological grades (Gleason score 7) that showed two
      distinctive growth patterns with different pathologies, that is, Gleason grades 3
      and 4 (G3 and G4). The G3 and G4 tumor specimens were taken from spatially
      separated regions within the cancer mass. Array-based comparative genomic
      hybridization (aCGH) was performed to obtain genotypes from the 10 pairs of G3
      and G4 cancer areas. The cancer DNAs were retrieved from formalin-fixed and
      paraffin-embedded tissues allowing optimal recognition and selection of target
      cells. A genome-wide 2,400-element BAC array that provided high-resolution
      detection of both deletions and amplifications was used. In the 20 G3 and G4
      areas, 252 genomic aberrations (88 gains, 164 deletions) were noted, of which 86
      were concurrent in G3 and G4 areas (34% overlap). Ninety-five of the 252
      alterations were defined by a single BAC clone (54 gains, 41 deletions).
      Overlapping changes were more frequent for deletions (46%) than for gains (13%).
      Frequent coinciding deletions (> or = 20% of tumors) were seen on 8p (60%), 6q
      (30%), 1p (20%), 2q (20%), proximal 8q (20%), 10q (20%), 13q (20%), 16q (20%),
      and 18q (20%). A frequent overlapping gain (> or = 20% of tumors) was detected on
      distal 13q (20%). The patterns of imbalance could be found to coincide in the G3
      and G4 areas of the majority of cancers. Array-based CGH can be used as a tool
      for the evaluation of genetic patterns in prostate cancer.

PMID- 14732927
TI  - Intronic deletion affecting a negative regulatory region of TP73 is related to
      breast and colorectal carcinomas.
AB  - The TP73 gene encodes a nuclear protein that has high homology with TP53. TP73 is
      rarely mutated in human cancer. The presence of a 1-kb regulatory fragment within
      the first intron of TP73 was recently reported. This fragment exerts silencer
      activity on TP73 mediated by ZEB. We searched for possible mutations in this
      negative regulatory region in 45 colorectal and 43 breast cancer patients and in
      34 healthy donors. The study was carried out using the SSCP method, and the
      allelic variants detected were sequenced. The expression of TP73 was analyzed by
      quantitative RT-PCR, and loss of heterozygosity (LOH) was assessed by
      microsatellite study. In several samples, we identified an allele variant that
      corresponds to a deletion of 73 bp in tumor tissues and normal counterparts,
      localized between -489 and -417 from the ATG start site of exon 2. Among the 88
      tumor samples, 35 (40%) showed at least 1 allele with the cited deletion, versus
      7 of the 34 (21%) healthy donors (P = 0.045). When we classified the patients
      according to the number of variations into homozygous or heterozygous groups, the
      significance was clearer (P = 0.03). No LOH was detected in the heterozygous
      cases. There was a positive quantitative correlation between the expression of
      TP73 and the presence of the allelic variant (P = 0.029). These data suggest that
      this allelic variant is common in breast and colorectal cancers and that it could
      alter the expression of the TP73 gene with an additive effect.

PMID- 14732928
TI  - A survey of the year 2002 commercial optical biosensor literature.
AB  - We have compiled 819 articles published in the year 2002 that involved commercial
      optical biosensor technology. The literature demonstrates that the technology's
      application continues to increase as biosensors are contributing to diverse
      scientific fields and are used to examine interactions ranging in size from small
      molecules to whole cells. Also, the variety of available commercial biosensor
      platforms is increasing and the expertise of users is improving. In this review,
      we use the literature to focus on the basic types of biosensor experiments,
      including kinetics, equilibrium analysis, solution competition, active
      concentration determination and screening. In addition, using examples of
      particularly well-performed analyses, we illustrate the high information content
      available in the primary response data and emphasize the impact of including
      figures in publications to support the results of biosensor analyses.

PMID- 14732929
TI  - A survey of the year 2002 literature on applications of isothermal titration
      calorimetry.
AB  - Isothermal titration calorimetry (ITC) is becoming widely accepted as a key
      instrument in any laboratory in which quantification of biomolecular interactions
      is a requisite. The method has matured with respect to general acceptance and
      application development over recent years. The number of publications on ITC has
      grown exponentially over the last 10 years, reflecting the general utility of the
      method. Here all the published works of the year 2002 in this area have been
      surveyed. We review the broad range of systems to which ITC is being directed and
      classify these into general areas highlighting key publications of interest. This
      provides an overview of what can be achieved using this method and what
      developments are likely to occur in the near future.

PMID- 14732930
TI  - A possible molecular mechanism of hanatoxin binding-modified gating in voltage
      gated K+-channels.
AB  - While S4 is known as the voltage sensor in voltage-gated potassium channels, the
      carboxyl terminus of S3 (S3C) is of particular interest concerning the site for
      gating modifier toxins like hanatoxin. The thus derived helical secondary
      structural arrangement for S3C, as well as its surrounding environment, has since
      been intensively and vigorously debated. Our previous structural analysis based
      on molecular simulation has provided sufficient information to describe
      reasonable docking conformation and further experimental designs (Lou et al.,
      2002. J. Mol. Recognit. 15: 175-179). However, if one only relies on such
      information, more advanced structure-functional interpretations for the roles S3C
      may play in the modification of gating behavior upon toxin binding will remain
      unknown. In order to have better understanding of the molecular details regarding
      this issue, we have performed the docking simulation with the S3C sequence from
      the hanatoxin-insensitive K+-channel, shaker, and analyzed the conformational
      changes resulting from such docking. Compared with other functional data from
      previous studies with respect to the proximity of the S3-S4 linker region, we
      suggested a significant movement of drk1 S3C, but not shaker S3C, in the
      direction presumably towards S4, which was comprehended as a possible factor
      interfering with S4 translocation during drk1 gating in the presence of toxin. In
      combination with the discussions for structural roles of the length of the S3-S4
      linker, a possible molecular mechanism to illustrate the hanatoxin binding
      modified gating is proposed.

PMID- 14732931
TI  - Structure-based discovery of a new affinity ligand to pancreatic alpha-amylase.
AB  - A ligand useful for affinity capture of porcine pancreatic alpha-amylase was
      found by virtual screening of the commercially available compound data base MDL
      Available Chemicals Directory. Hits from the virtual screening were investigated
      for binding by nuclear magnetic resonance (NMR) and surface plasmon resonance.
      Selected compounds were tested for inhibition of the enzyme using a NMR-based
      assay. One of the binders found was covalently coupled to a chromatographic resin
      and a column, packed with this resin, could retain alpha-amylase, which
      subsequently was eluted by introduction of the known inhibitor acarbose to the
      elution buffer.

PMID- 14732932
TI  - Molecular imprinting of nitrophenol and hydroxybenzoic acid isomers: effect of
      molecular structure and acidity on imprinting.
AB  - Three nitrophenol isomer-imprinted polymers were prepared under the same
      conditions using 4-vinylpyridine as a functional monomer. Different recognition
      capacities for template molecules were observed for the three polymers. Another
      imprinting system with stronger acidity than nitrophenol isomers, 2
      hydroxybenzoic acid (salicylic acid) and 4-hydroxybenzoic acid, was imprinted
      using 4-vinylpyridine or acrylamide as functional monomer respectively. Both 4
      hydroxybenzoic acid-imprinted polymers using the two monomers showed recognition
      ability for the template molecule. However, when acrylamide was chosen as
      functional monomer, the salicylic acid-imprinted polymer showed very weak
      recognition for the template molecule, whereas strong recognition ability of the
      resultant polymer for salicylic acid was observed with 4-vinylpyridine as
      functional monomer. It seems that the structure and acidity of template molecules
      is responsible for the difference in recognition, by influencing the formation
      and strength of interaction between template molecule and functional monomer
      during the imprinting process. An understanding of the mechanism of molecular
      imprinting and molecular recognition of MIPs will help to predict the selectivity
      of MIPs on the basis of template molecule properties.

PMID- 14732933
TI  - Immunomodulation by the copolymer glatiramer acetate.
AB  - Glatiramer acetate (GA; Copaxone, also known as Copolymer 1 or Cop-1), a
      copolymer of amino acids, is very effective in the suppression of experimental
      autoimmune encephalitis (EAE), the animal model for multiple sclerosis (MS), in
      various species including primates. The immunological cross-reaction between the
      myelin basic protein and GA serves as the basis for the suppressive activity of
      GA in EAE, by the induction of antigen-specific suppressor cells. The mode of
      action of GA is by initial strong promiscuous binding to major histocompatibility
      complex class II molecules and competition with MBP and other myelin proteins for
      such binding and presentation to T cells. Suppressor T cells induced by GA are of
      the Th2 type, migrate to the brain and lead to in situ bystander suppression.
      Clinical trials with GA, both phase II and phase III, were performed in relapsing
      remitting MS (RRMS) patients, and demonstrated efficacy in reducing the relapse
      rate, decreasing MRI-assessed disease activity and burden and slowing progression
      of disability. GA is generally well tolerated and is not associated with
      influenza-like symptoms and formation of neutralizing antibodies seen with beta
      interferons. It exerts its suppressive effect primarily by immunomodulation, and
      has recently shown ameliorating effect in a few additional autoimmune disorders
      as well as in graft rejection. At present GA is considered a valuable first-line
      treatment option for patients with RRMS.

PMID- 14732934
TI  - Mass spectrometry in the biosynthetic and structural investigation of lignins.
AB  - Lignin, a resistant cell-wall constituent of all vascular plants that consists of
      ether and carbon-linked methoxyphenols, is still far from being structurally
      described in detail. The main problem in its structural elucidation is the
      difficulty of isolating lignin from other wood components without damaging lignin
      itself. Furthermore, the high number and variegated forms of linkages that occur
      between the monomeric units and the chemical resistance of certain ether bonds
      limit the extent to which analytical and degradation procedures can be used to
      elucidate the lignin structure. Most of our present knowledge about the molecular
      structure of lignin is based on the analysis of monomers, dimers or, at the most,
      tetramers of degraded isolated lignins. Mass spectrometry (MS), which offers
      advantages in terms of speed, specificity, and sensitivity, has revealed to be a
      very powerful technique in the structural elucidation of lignins, in combination
      with the great number of chemical and thermal degradation methods available in
      the study of lignin. Moreover, the recent development of new ionization
      techniques in MS-electrospray ionization (ESI)-MS and matrix-assisted laser
      desorption/ionization (MALDI)-MS-has provided new possibilities to also analyze
      the undegraded lignin macromolecule.

PMID- 14732935
TI  - BIRD (blackbody infrared radiative dissociation): evolution, principles, and
      applications.
AB  - Blackbody infrared radiative dissociation (BIRD) describes the observation of ion
      dissociation reactions at essentially zero pressure by the ambient blackbody
      radiation field, which is usually studied in the ion-trapping ion cyclotron
      resonance (ICR) mass spectrometer. A brief summary of the historical context and
      evolution is provided. Focussing on the quantitative observation of the
      temperature dependence of BIRD rates, methods are developed for connecting BIRD
      observations with activation parameters and dissociation thermochemistry. Three
      regimes are differentiated and described, comprising large molecules, small
      molecules, and intermediate-sized molecules. The different approaches to
      interpreting BIRD kinetics in those three regimes are discussed. In less than a
      decade since its inception, this approach to studying gas-phase ions has spread
      over a wide variety of applications, which are surveyed. Some major areas of
      activity are: the characterization of solvent-molecule detachment from solvated
      ions; dissociation reactions of biomolecules (polypeptides, oligonucleotides,
      complexes involving polysaccharides) and the structural information to be deduced
      from them; and dissociations of proton-bound and metal-ion-containing complexes.
      Studies of blackbody-radiation-driven evaporation of water molecules from large
      water-cluster ions are surveyed briefly. Several techniques related to BIRD are
      noted, including collisional dissociation in the FT-ICR ion trap; high-pressure
      thermal dissociation in quadrupole ion traps and in heated inlet capillary
      regions; hot-filament-assisted dissociation; and infrared multiphoton
      dissociation (IRMPD).

PMID- 14732937
TI  - Cross-reactivity and sulfonamide antibiotics.

PMID- 14732938
TI  - Cross-reactivity and sulfonamide antibiotics.

PMID- 14732939
TI  - Combined estrogen-progestin oral contraceptives.

PMID- 14732940
TI  - Report of the Therapeutics and Technology Assessment Subcommittee of the American
      Academy of Neurology.

PMID- 14732941
TI  - Major malformations in offspring of women with epilepsy.

PMID- 14732942
TI  - Springtime for obstetrics and gynecology: will the specialty continue to blossom?

PMID- 14732943
TI  - ["Hypertension and diabetes screening and awareness" -- (HYDRA) study].

PMID- 14732944
TI  - [Aim, design and methods of the "Hypertension and diabetes screening and
      awareness" -- (HYDRA) study].
AB  - Aim of the study is a comprehensive clinical-epidemiological description of the
      prevalence of arterial hypertension and diabetes among primary care patients
      along with an assessment of doctor's recognition rates and prescription
      behaviour. The paper describes methods and design of the study and provides
      background information on the sampling process, instruments used as well as
      characteristics of doctors and patients. The study is based on a nationally
      representative sample of 1,912 primary care doctors and 45,000 patients that
      attended the doctors' office on the target days. The patients were also
      characterized by laboratory tests. The first stage of study consisted of a
      comprehensive description of the doctors' characteristics in terms of
      psychosocial, qualification- and provider aspects as well as attitudes towards
      hypertension and diabetes and their management. In the second stage all patients
      completed a questionnaire to describe their health behaviour and attitudes as
      well as the treatment history and therapy. In the third stage all patients were
      characterized by their doctors in terms of their diagnostic status and their past
      and current interventions.

PMID- 14732945
TI  - [Management of diabetes and hypertension: how do primary care physicians judge
      their performance?].
AB  - With regard to the management of hypertension and diabetes, HYDRA reveals that
      doctors report multiple problems in their everyday practice. Being confronted
      with an average of 73 patients a day, with almost every second having either
      diabetes or hypertension, frequently associated with multiple comorbid
      conditions, the core obstacle is the time factor. Doctors do not have sufficient
      time to perform diagnostic tests and especially no time for non-drug
      interventions of any type. Further available treatment guidelines are only used
      in 1 out of 2 doctors. Further they seem not to affect doctors performance
      significantly.

PMID- 14732946
TI  - [Hypertension, diabetes mellitus and comorbidity in primary care].
AB  - Almost every second patient seeing a primary care doctor suffers from arterial
      hypertension and about every fifth has diabetes mellitus. These diseases often
      occur at the same time. They are associated in more than 80% of the cases with
      other severe concomitant and subsequent diseases (heart attack, stroke, renal
      failure, neuropathy etc.). The magnitude especially of subsequent and concomitant
      diseases, the dimension of the personal suffering and the immense diagnostic and
      therapeutic challenges for the doctors have been massively underestimated so far.
      The article informs about the prevalence of the above disease, and structure of
      the problem. Before the background of an extremely high patient load seen by
      German General Physicians, the mainstay challenge is highlighted how to achieve
      further improvements of the quality of care on the basis of scientific guidelines
      alone, without a concomitant change in the system structure.

PMID- 14732948
TI  - [Diabetes, hypertension and microalbuminuria in primary care].
AB  - Microalbuminuria has been widely appreciated in recent years to be a valuable
      risk marker for an increased cardiovascular disease morbidity and mortality. Thus
      guidelines for the treatment of type-2-diabetes in Germany and the US recommend
      an annual screening as soon as the diagnosis of diabetes is established and a
      quarterly control when microalbuminuria is present. While nationally
      representative epidemiologic data from the US have been available, data from
      Germany, especially from the primary care sector are missing. This is especially
      important in light of the gatekeeper function of the primary care physician. The
      "Hypertension and Diabetes Risk Screening Study" (HYDRA) has been identifying
      37.8% of patients with hypertension and diabetes to have a positive dipstick test
      for microalbuminuria on the study day while only 12.5% of these are diagnosed by
      the doctor as having nephropathy. These patients additionally show a high burden
      of associated comorbidities and thus call for early detection and intervention
      especially because effective therapy is available. Although screening for
      microalbuminuria is recommended in the guidelines the value of a routine
      screening for microalbuminuria in primary care is under recognized.

PMID- 14732947
TI  - [Microalbuminuria is an early marker for increased morbidity and mortality].
AB  - Recent studies have shown the beneficial effects of a blockade of the renin
      angiotensin system (RAS) not only for blood pressure reduction but also end organ
      protection. One of the markers that is closely correlated with the increased
      cardiovascular risk is microalbuminuria. A common mediator for the development of
      both, microalbuminuria and end organ damage seems to be Angiotensin II, the
      blockade of which apparently reduces microalbuminuria as well as end organ
      damage. Therefore we had a closer look into pathophysiology of microalbuminuria
      and the relevance for end organ damage and discuss current medical strategies to
      alleviate these diseases.

PMID- 14732949
TI  - [Nephropathy: an overview for daily practice].
AB  - The examination of renal function in the daily practice may give important
      information on the risk status of a given patient. For example, the diagnosis of
      microalbuminuria carries high predictive value for a future cardiovascular risk
      of patients with hypertension, diabetes, congestive heart failure, as well as
      myocardial infarction. The findings of the Hypertension and Diabetes Screening
      and Awareness Study (HYDRA) indicate that screening for microalbuminuria is
      performed not often enough in patients with diabetes or hypertension,
      respectively, and a positive screening finding often does not trigger necessary
      consequences as for additional diagnosis or therapy.

PMID- 14732950
TI  - Pharmacokinetic properties and their relation to certain physicochemical
      properties.

PMID- 14732951
TI  - Definition and determination of important pharmacokinetic parameters for dosage
      regimen (one compartment model).

PMID- 14732952
TI  - [A method of computerized evaluation of CT based treatment plants in external
      radiotherapy].
AB  - Selection of an optimal treatment plan requires the comparison of dose
      distributions and dose-volume histograms (DVH) of all plan variants calculated
      for the patient. Each treatment plan consists generally of 30 to 40 CT slices,
      making the comparison difficult and time consuming. The present study proposes an
      objective index that takes into account both physical and biological criteria for
      the evaluation of the dose distribution. The DHV-based evaluation index can be
      calculated according to the following four criteria: ICRU conformity (review of
      the differences between the dose in the planning target volume and the ICRU
      recommendations); mean dose and dose homogeneity of the planning target volume;
      the product of tumour complication probability (TCP) and normal tissue
      complication probability (NTCP); and finally a criterion that takes into account
      the dose load of non-segmented tissue portions within the CT slice. The
      application of the objective index is demonstrated for two different clinical
      cases (esophagus and breast carcinoma). During the evaluation period, the
      objective index showed a good correlation between the doctor's decision and the
      proposed objective index. Thus, the objective index is suitable for a computer
      based evaluation of treatment plans.

PMID- 14732953
TI  - Absorbed dose determination for high energy photon and electron beams at a PRIMUS
      linear accelerator using the documents DIN 6800-2 and TRS-398.
AB  - The International Atomic Energy Agency in Vienna has recently published a new
      Code of Practice for absorbed dose determination in external beam radiotherapy
      (Technical Reports Series No. 398). This code claims to fulfill the need for a
      systematic and internationally unfied approach to the calibration of ionization
      chambers, as well as to the use of these detectors in determining the absorbed
      dose to water for the radiation beams used in radiotherapy. In Germany, the
      corresponding national norms are laid down in DIN 6800-2. Therefore, it appeared
      necessary to compare in detail the procedures and results obtained according to
      these two documents. The comparison was performed for a 6 MV and 15 MV photon
      beam, as well as for a 12 MeV and 18 MeV electron beam. Although a series of
      differences could be ascertained, in particular in the numerical values of the
      various perturbation factors, the agreement of the final results remained well
      within the expected uncertainty range. Nevertheless, it is suggested to modify
      DIN 6800-2 in order to make it more easily applicable to a hospital environment,
      to incorporate the progress of knowledge in the data involved, and to achieve a
      better adherence to international recommendations.

PMID- 14732954
TI  - [Radiation exposure to personnel in cardiac catheterization laboratories].
AB  - Radiation exposure in personnel of cardiac catheterization units is based on
      local dosimetry during patient investigations. In the present study, dose rates
      were measured at various heights in representative locations, with and without
      fixed radiation protection shields in place. To determine the effective dose
      values, TLD measurements were performed using on Alderson phantom to generate
      radiation scatter and a second phantom in the position of the cardiologist
      performing the catheterization. Various types of personal radiation protection
      garment and fixed shields were considered in the calculations. Our results
      indicate on one hand that good protective standards can be achieved with
      effective doses below 1 mSv/year under optimized conditions. On the other hand,
      inappropriate radiation protection equipment can cause substantial increase of
      radiation doses. Alone the lack of a thyroid shield increases the effective dose
      of the cardiologist by a factor of 3. For the personnel, effective doses were
      generally higher than personal doses by a factor between 1.5 and 4.8 depending on
      the radiation protection situation.

PMID- 14732955
TI  - [State of measures of quality assurance for radiotherapy units in Switzerland].
AB  - In Switzerland 57 X-ray therapy units are in operation at present. According to
      the Swiss Ordinance on Radiation Protection, a quality-assurance program must
      regularly be applied in to these units. However, as the Swiss X-ray Ordinance
      gives explicit control parameters only for diagnostic units, the present article
      issues proposals for the realization of a quality-assurance program for the
      therapy units. In this regard, it is distinguished between checks performed by
      technical personnel of the X-ray manufacturers and checks performed by a medical
      physicist with corresponding qualification, or under his supervision. The so
      called mentor project for the performance of annual constancy checks in
      institutes without medical physicists is also taken into account. These proposals
      should be helpful for the discussion and clarification of competencies, hence
      contributing to standardization of control practices in Switzerland.

PMID- 14732956
TI  - [A fast procedure of patient set-up verification in pelvic radiotherapy].
AB  - Accuracy of patient positioning is an important aspect in radiation therapy. The
      present paper presents a new procedure for the determination of set-up errors in
      radiotherapy, which is based on a special form of the Fast Fourier Transform
      (FFT), i.e., the Fast Hartley Transform (FHT). The use of this method allows to
      compare in short time verification and simulator films, and to calculate the
      translation vector or the in-plane rotation of the patient. Standard deviations <
      1 mm for shifting measurements and < 1 degree for measurements of the rotation
      were detected, provided that the positioning remained within the common clinical
      range. The present results were in good agreement with data obtained using a
      landmark-based method.

PMID- 14732957
TI  - Quantitative image reconstruction in PET from emission data only using cluster
      analysis.
AB  - Quantitative image reconstruction in positron emission tomography requires
      attenuation correction. In case the attenuation correction is not measured
      separately, under certain conditions this can be determined from the emission
      data alone. We present a method based on cluster analysis that assumes only 3
      empirical attenuation coefficients, i.e., 0.095 cm-1 for soft tissue, 0.02 cm-1
      for lung, and 0 cm-1 for air. The subsequent image reconstruction takes place in
      an iterative fashion, through maximization of image likelihood. For the
      mathematical thorax phantom used in the present study, the results are comparable
      to those obtained after separate measurement of the attenuation correction.

PMID- 14732958
TI  - Dosimetry in the vicinity of a 192Ir brachytherapy line source in air.
AB  - Dose calculation in brachytherapy is based on the assumption that the radiation
      sources defining a matrix of dwell positions are point-like. The planning
      systems, however, do not sufficiently take into account the finite extension of
      the sources. The present study focused on the problem of dosimetry in the
      vicinity of a 192Ir brachytherapy line source, particularly for small source
      target distances (< 1 cm). Distance-dependent dose measurements were performed
      using a diamond detector with high spatial resolution. The measured distributions
      were then compared with dose calculations based on the extended version of the
      Sievert's integral for line sources. The first approach utilizes the classical
      Sievert's formulation. The second approach takes into account the finite
      extension of the detector surface, resulting in improved agreement with the
      measured dose distribution. Finally, the effect of self-attenuation within the
      source is also included. This further reduces the deviation between dose
      calculations and measurements.

PMID- 14732959
TI  - [Determination of absorbed dose to water for high energy photon and electron
      beams--comparison of different dosimetry protocols].
AB  - The determination of absorbed dose to water for high-energy photon and electron
      beams is performed in Germany according to the dosimetry protocol DIN 6800-2
      (1997). At an international level, the main protocols used are the AAPM dosimetry
      protocol TG-51 (1999) and the IAEA Code of Practice TRS-398 (2000). The present
      paper systematically compares these three dosimetry protocols, and identifies
      similarities and differences. The investigations were performed using 4 and 10 MV
      photon beams, as well as 6, 8, 9, 10, 12 and 14 MeV electron beams. Two
      cylindrical and two plane-parallel type chambers were used for measurements. In
      general, the discrepancies among the three protocols were 1.0% for photon beams
      and 1.6% for electron beams. Comparative measurements in the context of
      measurement technical control (MTK) with TLD showed a deviation of less than 1.3%
      between the measurements obtained according to protocols DIN 6800-2 and MTK
      (exceptions: 4 MV photons with 2.9% and 6 MeV electrons with 2.4%). While only
      cylindrical chambers were used for photon beams, measurements of electron beams
      were performed using both cylindrical and plane-parallel chambers (the latter
      used after a cross-calibration to a cylindrical chamber, as required by the
      respective dosimetry protocols). Notably, unlike recommended in the corresponding
      protocols, we found out that cylindrical chambers can be used also for energies
      from 6 to 10 MeV.

PMID- 14732961
TI  - Drug-drug interactions of beta-adrenoceptor blockers.
AB  - Patients with cardiovascular diseases are often treated by concurrent multiple
      drug therapy. It is therefore plausible that with an increasing number of drugs
      the risk of drug interactions increases. Such interactions can be either
      pharmacodynamic (and are due to the mechanism of the administered drugs) or they
      can be pharmacokinetic (resulting in a reduction or enhancement of drug
      elimination). Pharmacokinetic interactions can be either due to interactions at
      the level of drug metabolizing enzymes (most important cytochrome P450 (CYP)
      enzymes) or interactions at the level of drug transporter proteins (for example P
      glycoprotein (MDR1)). It is important to distinguish between both mechanisms
      because interactions at transporter proteins can be attributed to those drugs
      that are not enzymatically metabolized. The scope of this article is to give an
      overview on clinically relevant interactions of the four beta-blockers widely
      used in the therapy of cardiovascular diseases namely atenolol (CAS 29122-68-7),
      bisoprolol (CAS 66722-44-9), metoprolol (CAS 37350-58-6) (each beta-1 selective),
      and carvedilol (CAS 72956-09-3) (beta-1 and beta-2 nonselective). Among these
      beta-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in
      part excreted as parent compound via the renal route (50%), the other 50% are
      hepatically metabolised, whereas metoprolol and carvedilol are metabolised by
      CYP2D6. In addition, evidence is accumulating that carvedilol is a substrate for
      P-glycoprotein. For these four beta-blockers various pharmacodynamic and
      pharmacokinetic interactions have been demonstrated. Such interactions that
      result in an altered pharmacokinetics are mainly observed with those beta
      blockers that are excreted via metabolism (metoprolol and carvedilol).
      Accordingly these drugs have a higher potential for drug interactions. However,
      it should be emphasized that, in general, beta-blockers are well tolerated safe
      drugs with a large therapeutic index.

PMID- 14732960
TI  - Development of new vaccines against meningococcal disease.
AB  - Meningococcal diseases continue to have a major public health impact in many
      countries. Five major groups of Neisseria meningitidis (A, B, C, Y and W135) are
      responsible for most meningoccocal diseases. Plain polysaccharides vaccines for
      Nelsseria meningitidis groups A, C, Y and W-135 have been in use for
      approximately 20 years, both to prevent invasive disease in high-risk population
      and to control disease outbreaks. However, these conventional meningococcal
      vaccines induce a relatively short-lasting T-cell independent immune response,
      are not effective in children under two years of age and can induce
      hyporesponsiveness. New meningococcal group C conjugate vaccines have since been
      developed, which offer solid advantages over the currently licensed plain
      polysaccharide vaccines. There is still no vaccine available against the
      serogroup B, which is a major cause of invasive disease. This report summarises
      the different approaches to the development of vaccines against the pathogenic
      meningococci.

PMID- 14732962
TI  - Antioxidative, antiproliferative and biochemical effects in HepG2 cells of a
      homeopathic remedy and its constituent plant tinctures tested separately or in
      combination.
AB  - Hepeel is a homeopathic remedy commonly used to treat primary and secondary
      functional disorders of the liver. It consists of highly diluted extracts from
      the following plants: Chelidonium from Chelidonium majus, L., Carduus marianus
      from Silybum marianum, L., Veratrum from Veratrum album L., Colocynthis from
      Citrullus colocynthis L., Lycopodium from Lycopodium clavatum L., Nux moschata
      from Myristica fragans, Houtt, and China from Cinchona pubescens, Vahl. The
      antioxidative, antiproliferative and biochemical effects in HepG2 hepatoblastoma
      cells of serial dilutions of these plant tinctures were tested, either separately
      or in various combinations. Upon damage of the cells with tert-butyl
      hydroperoxide, Carduus marianus, China and Nux moschata, in decreasing order,
      showed the strongest antioxidative effects. Greater than 95% inhibition of total
      production of malondialdehyde was reached with these three tinctures at dilutions
      of D4. The complete combination of the tinctures (COMB) realised in the
      homeopathic remedy showed an effect corresponding to the combined effects of the
      individual tinctures. The antiproliferative influence on the incorporation of 3H
      thymidine into DNA in normal HepG2 cells was significant (p < 0.01) but
      relatively weak, and decreased in the order Carduus marianus, Chelidonium,
      Colocynthis and Veratrum. At a dilution of D4 Colocynthis showed the strongest
      inhibition (13.5%). The effect of the combination of Colocynthis and Veratrum was
      markedly higher (22.3%) than that of the individual tinctures, but was not
      additive. With this combination, cell numbers were reduced. COMB had similar
      effects on proliferation and cell numbers, with the antiproliferative effect
      starting at a dilution of 1:40. The conjugation of 3,4-dichloronitrobenzene with
      glutathione was induced only by Carduus marianus and COMB, while all other
      tinctures were ineffective. Neither the individual tinctures, nor COMB showed
      cytotoxic effects in the dilutions tested. These results demonstrate that the
      complete combination (COMB) realised in the homeopathic remedy and its
      constituents exert specific antioxidative, antiproliferative and biochemical
      effects on HepG2 cells which all point to a potential hepatoprotective and
      tumouristatic action.

PMID- 14732963
TI  - Synthesis and antidiabetic activity of some new furochromonyl-2,4
      thiazolidinediones.
AB  - A new series of furochromone-2,4-thiazolidinedione derivatives (VIIa-h) was
      prepared by Knoevenagel reaction of substituted-2,4-thiazolidinediones (VIa-h)
      with Khellin-2-carboxaldehyde (IV). The prepared compounds were tested for their
      insulinotropic activities in INS-1 cells. Compounds VIId and VIIf (at lower
      concentration; 1 microgram/ml) were able to increase insulin release in the
      presence of 5.6 mmol/l glucose. Both these compounds (VIId and VIIf) and VIIg
      increased glucose uptake in NIH-3T3 cells. Thus these 3 compounds should be
      tested for antidiabetic effects in vivo.

PMID- 14732964
TI  - Effect of the dimeric bile acid analogue S 0960, a specific inhibitor of the
      apical sodium-dependent bile salt transporter in the ileum, on the renal handling
      of taurocholate.
AB  - The effect of the dimeric bile acid analogue S 0960 (CAS 142974-51-4), a specific
      inhibitor of the apical sodium-dependent bile salt transporter (ASBT) in the
      ileum, on kidney function was studied by clearance experiments in anesthetized
      rats. Additional experiments were performed on proximal tubular cells freshly
      isolated from rat kidney cortex and enriched by nycodenz density gradient
      centrifugation. The clearance studies, which were performed after a 5 h bile duct
      ligation, revealed a marked rise of the 3H-taurocholate clearance (from 85.4 +/-
      15.7 to 371.1 +/- 86.0 microliters/min 100 g b.w., p < 0.05) and a considerable
      fall of the fractional tubular 3H-taurocholate reabsorption (from 90.2 +/- 1.72
      to 68.2 +/- 7.50%, p < 0.05) after S 0960 at a dose of 10 mg/kg i.v. whereas the
      glomerular filtration rate did not significantly change (from 919 +/- 165 to 1055
      +/- 162 microliters/min/100 g b.w.). Isolated proximal tubular cells showed a
      significant accumulation of 3H-taurocholate. The 3H-taurocholate cell/bath
      concentration ratio amounted to 3.34 +/- 0.17 at a 3H-taurocholate bath
      concentration of 3 x 10(-7) mol/l. LiCl (10(-3) mol/l), which is known to inhibit
      sodium-dependent transport processes in the kidney, markedly diminished cellular
      3H-taurocholate uptake (by 65.8%) whereas probenecid (CAS 57-66-9, 10(-4) mol/l),
      the classical inhibitor of the basolateral organic acid transporter in the
      kidney, did not significantly affect 3H-taurocholate uptake. This finding
      indicates that transport of taurocholate by the basolaterally located organic
      acid transporter is not involved in the uptake process. The kinetic studies
      revealed an apparent K(m) value of 31 mumol/l and a Vmax value of 6.7 mumol/l
      cell water/min for tubular 3H-taurocholate uptake. At concentrations > 30 mumol/l
      S 0960 virtually completely inhibited cellular 3H-taurocholate uptake. 3H
      taurocholate uptake was half-maximally inhibited at a S 0960 concentration of 5.8
      mumol/l. The results of this functional study are in line with recent molecular
      evidence that the apical sodium-dependent bile salt transporters in kidney and
      ileum are identical and demonstrate that S 0960 is a potent inhibitor of the
      apical sodium-dependent taurocholate transporter in the kidney which augments the
      renal clearance of 3H-taurocholate. Compounds such as S 0960 may be of special
      therapeutical value in patients with extrahepatic cholestasis and elevated levels
      of plasma bile acids.

PMID- 14732965
TI  - General pharmacology of the butanamide derivative S 19812, a new dual inhibitor
      of cyclooxygenase and lipoxygenase pathways.
AB  - S 19812 (N-hydroxy-N-methyl-4-(2,3-bis-(4-methoxyphenyl)-thiophen-5-yl)
      butanamide, CAS 181308-68-9), a dual inhibitor of cyclooxygenase and lipoxygenase
      pathways, was evaluated in different models of pain and inflammation. Its gastric
      tolerance was also investigated. After acute oral treatment S 19812 exhibited a
      non-opioid analgesic activity observed in the phenylbenzoquinone-induced writhing
      model in mice (ED50 = 2.1 mg/kg) and in the carrageenan-induced hyperalgesia
      model in rats (ED50 = 9.1 mg/kg, preventive treatment; 8.3 mg/kg, curative
      treatment). Anti-inflammatory activity was observed in the adjuvant-induced
      arthritis in rat (inhibition of edema ED50 = 11 mg/kg/day p.o., day 28). In rats
      and mice, S 19812 exhibited an excellent gastric tolerance at doses up to 800
      mg/kg p.o.

PMID- 14732966
TI  - Synergetic analgesic effect of the combination of arnica and hydroxyethyl
      salicylate in ethanolic solution following cutaneous application by
      transcutaneous electrostimulation.
AB  - A combination of the active agents arnica and hydroxyethyl salicylate (HES) in
      ethanolic solution (Sportino Acute Spray) is cutaneously applied for the
      treatment of sports injuries and diseases of the locomotor apparatus. The aim was
      to examine the efficacy and synergism of the single substances and the
      combination with regard to the analgesic effect after cutaneous application as
      well as to validate the method of transcutaneous electronic stimulation as a
      method of measuring the analgesic effect. In the present article, the method of
      transcutaneous electrostimulation was used in a randomized, controlled, single
      blind trial on healthy volunteers to provide objective evidence that the
      combination of active agents displays a significantly greater analgesic effect
      than the individual active agents. Thus there is synergy between the active
      agents arnica and hydroxyethyl salicylate in the combination preparation. In
      addition, the effect of the vehicle ethanol and the reference substance water
      could be determined within the framework of these comparative experiments and the
      difference between the combination preparation and the individual substances
      arnica and HES could be shown. The method of transcutaneous electrostimulation
      used for the objective measurement of the analgesic effect was validated.

PMID- 14732968
TI  - [Guidelines and methods for clinical investigation of drugs for treatment of
      stable angina pectoris].
AB  - To prove the antianginal efficacy of drugs in patients with stable angina
      pectoris the notice of certain criteria is necessary for the planning and
      performance for the clinical investigation of medicinal products. They consist of
      the study design, the randomization, blinding, inclusion and exclusion criteria,
      definition of endpoints, the performance of the study, the doses and dosing
      scheme, the methods of investigation, the sample size estimation and the
      evaluation of the results. If there will be not paid enough attention to these
      criteria and conditions false positive but also false negative results can arise.
      The criteria necessary for proving the antianginal efficacy in patients with
      stable angina pectoris will be presented.

PMID- 14732967
TI  - Synthesis and antifilarial evaluation of 7-O-acetamidyl-4-alkyl-2H-1-benzopyran-2
      ones.
AB  - A series of 7-O-acetamidyl-4-alkyl-2H-1-benzopyran-2-ones (5-23) has been
      synthesized by amidation of 7-O-(carbethoxymethyl)-4-alkyl-2H-1-benzopyran-2-ones
      (2a, 2b) with different primary and secondary amines in fair to good yield. The
      resulting compounds were screened for their filarial DNA topoisomerase inhibitory
      activity under in vivo condition in Setaria cervi. The compounds were tested in
      vitro against Brugia malayi. A few of the compounds possess promising
      antifilarial activity.

PMID- 14732969
TI  - [Heterotopic osteogenesis of autogenous marrow stromal cells with recombinant
      human bone morphogenetic protein 2 gene transfection and porous calcium phosphate
      ceramic as a scaffold].
AB  - OBJECTIVE: To observe the heterotopic osteogenesis of autogenous marrow stromal
      cells loading on porous calcium phosphate ceramic scaffolds with rhBMP2 gene
      transfection in a Sprague-Dawley rat model. METHODS: Autogenous marrow stromal
      cells were obtained from left femurs and tibias of 20 male adult SD rats under
      general anesthesia and sterile condition and cultured in alpha-Minimal Essential
      Medium supplemented with 15% fetal bovine serum. RhBMP2 gene was transfected into
      stromal cells by means of LipofectAMINE 2000 reagent five days after primary
      culture. The stably gene expressive cells were selected with G-418 for 14 days
      and mixed with stromal cells without transfection. The mixture cells were seeded
      and subcultured for another 10 days in porous calcium phosphate bioceramic that
      had been subjected to surface-modification via soaking in human plasma
      fibronectin. The cell-ceramic compound was implanted subcutaneously and
      intramuscularly in the corresponding rat. Lab animals were sacrificed at two-week
      intervals till twenty weeks postoperatively and the involved samples were
      removed. RESULTS: Morphologic and histological study demonstrated that cell
      ceramic compound had an ability of heterotopic osteogenesis, which was similar to
      that of autogenous osteoblasts in previous study. CONCLUSION: It seems that
      autogenous stromal cells with rhBMP2 transfection acts as a bioreactor promoting
      proliferation and differentiation of stem cells when they are replanted into the
      corresponding animals.

PMID- 14732970
TI  - [The experimental study of PDLLA/rhBMP-2 compound screws for internal fixation of
      mandibular fracture].
AB  - OBJECTIVE: To study the effect of poly D,L-lactic acid (PDLLA) screws with PDLLA
      rhBMP compound on bone regeneration in the screw holes and fracture ends of dog
      mandibles. METHODS: A self-control study was carried out in 4 dogs. PDLLA/rhBMP-2
      compound screws were implanted to fix the mental fractures and PDLLA screws were
      used as control. The samples from mandibles were collected at 4, 8, 12, 16 weeks
      after implantation and observed by radiography and histology. RESULTS: All dogs
      showed a greater degree of bone regeneration around PDLLA/rhBMP-2 screws than
      PDLLA ones and all fractures were fixed and healed well. CONCLUSION: The PDLLA
      rhBMP screw has a better effect of inducing osteogenesis than PDLLA screw, and is
      able to exert a good fixation to fracture.

PMID- 14732971
TI  - [Chemical synthesis of biodegradable poly-para-dioxanone and its application for
      mandibular fracture fixation].
AB  - OBJECTIVE: To observe mandibular fracture healing after synthesized bioabsorable
      poly-para-dioxanone (PDS) ligature fixation. METHODS: Para-dioxanone monomer was
      prepared by chemical reactions of metallic sodium, ethylene glycol and other raw
      materials. PDS was synthesized by polymerizing the purified para-dioxanone in the
      presence of catalyst under the conditions of negative pressure and certain
      temperature. PDS ligature was obtained by processing the polymer into small
      granules, drying and melt-extruding through a spinnerette. Eighteen adult male
      New Zealand rabbits were assigned randomly into two groups. After mandibular
      fracture models were created, reductions of the artificial fractures were
      accomplished by means of transosseous PDS ligatures on each of 12 rabbits in
      experimental group. While the other six rabbits without any internal fixation
      were set as control. Schedules for killing were arranged to give postoperative
      samples at two-week interval till 12th week. RESULTS: Radiographical and
      histological examinations demonstrated that all fractures fixed with PDS
      ligatures healed without any complication. Periosteal and cartilaginous
      osteogenesis was observed in newly formed external callus. In contrast, bone
      fragment migration and the consequent nonunion occurred in the control group. PDS
      ligature degraded and absorbed without interference with osseous union and
      healing. The tensile strength reduction of PDS ligature was prior to its
      absorption in vivo. CONCLUSION: The synthesized PDS is a colorless, flexible,
      themoplastic and monofilament fiber, which can be sterilized by ethylene oxide
      embalmment without serious loss of tensile strength. It seems that the
      application of this macromolecular material in internal fixation is of great
      worth for further study.

PMID- 14732972
TI  - [Behavior of bone formation around the porous-hollow cylindrical titanium implant
      composed of bone morphogenetic protein].
AB  - OBJECTIVE: The purpose of this study was to observe the behavior of bone
      formation around the titanium-hollow porous cylinder implant composed of bovine
      bone morphogentic protein(bBMP). METHODS: Porous-hollow cylinder titanium implant
      composed of bBMP was implanted into mandibule of dogs. Multiple fluorescent was
      labeled at different times and then LSCM was used to observe the newly formed
      bone around the complex implant. RESULTS: The newly formed bone around the
      complex implant in experimental group was more obvious than that in other groups.
      CONCLUSION: Earlier, longer and more new-bone formation can be induced by porous
      hollow cylinder titanium implant composed of bBMP, and LSCM is an effective
      method to observe new bone formation around implant.

PMID- 14732973
TI  - [Functional reconstruction with tissue engineered myoblast in facial muscle of
      rat].
AB  - OBJECTIVE: The purpose of this article is to discuss the reconstruction of facial
      muscle defects with tissue engineered myoblast in SD rats. METHODS: Using
      purified, subcultured myoblast of neonatal rats and type I collagen gels as
      extracellular matrix (ECM) and scaffold, tissue engineered muscle was
      transplanted in the face of syngeneic nutured rats. RESULTS: Tissue engineered
      myoblast generated and differentiated in vitro were observed with microscope.
      Myoblast fused each other and formed myofibers in the face of rats, nerve fibers
      and vessels regeneration could also be found in some samples. Postoperative
      electromiographs showed the myofibers were active when stimulating the nerve
      trunk that innervates the engineered facial muscle. CONCLUSION: Tissue engineered
      method is hopeful to be used as a new technique to reconstruct defects of facial
      muscle.

PMID- 14732974
TI  - [Immunohistochemical study of sialyl Lewis(a) antigen in oral squamous cell
      carcinoma: the association of sialyl Lewis(a) expression with local lymph
      metastasis].
AB  - OBJECTIVE: The purpose of this study was to screen sialyl Lewis(a) (sLe(a)) in
      the tumors of patients with oral squamous cell carcinoma (OSCC) and to explore
      the association of sialyl Lewis(a) expression with local lymph node metastasis.
      METHODS: Specimen from 38 patients with primary OSCC were obtained and analyzed
      by immunohistochemical methods. RESULTS: The expression of sLe(a) protein, but
      not E-selectin, of OSCCs significantly correlated to the local lymph node
      metastasis. sLe(a) was expressed in 79% (15/19) of the metastatic cases compared
      with 21% (4/19) of the non-metastasis ones, indicated the association of sLe(a)
      expression with the local lymph involvement. CONCLUSION: High expression of
      sLe(a) in OSCC may be related to the metastasis of cervical lymph nodes and it
      seems useful in predicting poor prognosis in OSCC.

PMID- 14732975
TI  - [The expression and function of Smad7 during human tooth germ development].
AB  - OBJECTIVE: To observe the temporal and spatial expression of Smad7 during human
      tooth germ development and evaluate the effect of Smad7 on tooth germ
      development. METHODS: The expression of Smad7 and its changes at different stages
      of human tooth germ were detected by using immunohistochemical staining. RESULTS:
      Smad7 was expressed at all stages of tooth germ, but the distribution patterns at
      various stages were different. It indicated that temporal and spatial expressing
      mode of Smad7 during human tooth germ development was specific, which was similar
      to that of TGF-beta its signal transducer Smad2/3. CONCLUSION: Smad7 might play
      an important role in TGF-beta intracellular signaling for modulating the
      differentiation of ameloblasts and odontoblasts.

PMID- 14732976
TI  - [Expression of human telomerase reverse transcriptase and bcl-2 in
      ameloblastoma].
AB  - OBJECTIVE: To study the expression of telomerase reverse transcriptase (hTERT)
      and bcl-2 in ameloblastoma (AB), METHODS: hTERT mRNA in 54 cases of AB (primary
      AB 31 cases, recurrent AB 17 cases, malignant AB 4 cases) and 7 cases of oral
      normal mucosa was detected by in situ hybridization, and bcl-2 by S-P method.
      RESULTS: The expression of hTERT mRNA was negative or weak in normal oral mucosa
      (14.3%), moderate or strong in AB (94.4%). There was a significant difference in
      these two groups (P < 0.001). The difference between the expressions of hTERT in
      primary, recurrent and malignant AB was significant (P < 0.05). The positive
      ratio of bcl-2 in AB and normal oral mucosa was respectively 88.0%, 44.4%. There
      was a significant statistical difference in these two groups (P < 0.001). hTERT
      mRNA was stronger in recurred or malignantly transformed AB (P < 0.05).
      CONCLUSION: The expression of hTERT and bcl-2 is stronger in recurred or
      malignantly transformed AB, and it could be used as an indicator of AB prognosis.
      Telomerase activity and bcl-2 expression play an important role in genesis and
      development of AB.

PMID- 14732977
TI  - [Effect of local immunotherapy of interleukin 2(IL-2) in combination with
      chemotherapy upon intratumoral lymphocytes in oral squamous cell carcinomas].
AB  - OBJECTIVE: To evaluate the effect of locoregional immunotherapy of interleukin 2
      (IL-2) in combination with chemotherapy upon intratumoral lymphocytes in oral
      squamous cell carcinomas. METHODS: Thirty-four patients with stage T3 or T4 oral
      squamous cell carcinoma were randomly divided into two groups, and treated with
      two therapies. 23 cases of them received immunochemotherapy and 11 cases received
      PVP chemotherapy. Changes of T lymphocyte subsets and B cells at tumor site in
      the two groups were compared before and after therapy. RESULTS: The relative
      numbers of CD4+, CD8+, CD20+ before and after treatment in immunochemotherapy
      were respectively 36.96, 35.65, 28.65 and 56.61, 38.52, 38.70. The numbers of
      CD4+, CD20+ increased significantly after immunochemotherapy. However, in
      chemotherapy group, there was no significant difference in numbers of CD4+, CD8+
      and CD20+ cells between pre and post treatment. CONCLUSION: Immunochemotherapy
      for oral squamous cell carcinomas may play an important role in increasing local
      immunity.

PMID- 14732979
TI  - [The analysis of formant characteristics of vowels in the speech of patient with
      cleft palate].
AB  - OBJECTIVE: To analyze the formant frequency of vowels in the sequence therapy of
      patient with cleft palate. METHODS: The formant frequency of vowels [a], [e],
      [i], [u] of normal children and postoperative patients with and without speech
      therapy was measured and analyzed by VS-99. RESULTS: 1. The mean value of F1, F2,
      F3 of [a] did not show significant difference among the three groups (P > 0.05).
      2. The difference of mean value of [e] was significant between control group and
      pre-speech-therapy group, and between pre-speech-therapy and post-speech-therapy
      group (P < 0.05), but no significant difference was found between post-speech
      therapy and control group(P > 0.05). The mean value of the formant in post-speech
      therapy was higher than that of pre-speech-therapy. 3. The difference of mean
      value of [i] was significant between pre-speech-therapy and post-speech-therapy
      (P < 0.05), the mean value of F2, F3 in post-speech-therapy group decreased
      significantly compared with control (P < 0.05). 4. The difference of mean value
      of [u] showed significance between pre-speech-therapy and post-speech-therapy (P
      < 0.05), while the differences among other groups were insignificant (P > 0.05).
      CONCLUSION: Surgical repair of cleft palate cannot make all patients obtain
      perfect Velopharyngeal competence (VPC), while speech therapy can improve
      patient's pronunciation. Speech spectrum analysis can judge the effect of cleft
      palate therapy objectively.

PMID- 14732978
TI  - [Clinical application of anticancer nanoparticles targeting metastasis foci of
      cervical lymph nodes in patients with oral carcinoma].
AB  - OBJECTIVE: The aim of this study was to investigate the target delivery of
      Cucurbitacin BE (CuBE) to cervical lymph nodes by peri-oral-cancer submucosal
      injection of the average diameter 85 nm Cucurbitacin BE poly-lactic acid
      nanoparticles (CuBE-PLA-NP) and evaluate its clinical therapy efficacy. METHODS:
      CuBE and CuBE-PLA-NP were respectively injected into peri-oral-cancer submucosa
      at 2, 12, 24, 48, 72, 96, 120, 144, 168 and 192 hours before operation in 26
      patients with oral cancer. The concentrations of CuBE in cervical lymph nodes and
      blood were measured by high performance liquid chromatography (HPLC) at every
      time point. Cancer cell degeneration and necrosis in metastasis foci of cervical
      lymph nodes were observed using light microscope and electron microscope.
      RESULTS: (1) The CuBE concentrations in cervical lymph nodes after CuBE-PLA-NP
      injection were far higher than those after CuBE injection at every time point,
      the duration of CuBE existing in the cervical lymph nodes in CuBE-PLA-NP group
      was far longer than those in CuBE group, the area under the CuBE concentrations
      time curve of the cervical lymph nodes in CuBE-PLA-NP group was 43.67 times as
      many as that in CuBE group; (2) The CuBE ratio of maximum concentrations in the
      cervical lymph nodes in CuBE-PLA-NP group was 106.46 times as high as that in
      CuBE group; (3) The CuBE concentrations in the blood in CuBE-PLA-NP group was far
      lower than that in CuBE group; (4) Cancer cell necrosis and degeneration in the
      metastasis foci of cervical lymph nodes were found in CuBE-PLA-NP group, necrosis
      and degeneration were not found in CuBE group. CONCLUSION: The peri-oral-cancer
      submucosa injection of the average diameter of 85 nm CuBE-PLA-NP can specifically
      delivery CuBE to the cervical lymph nodes, enhance treatment efficiency, and
      reduce general toxicity.

PMID- 14732980
TI  - [Study on color masking ability of restoration material Vita Mark II].
AB  - OBJECTIVE: The purpose of this study was to evaluate the color masking ability of
      Computer Aided Design/Computer Aided Manufacture(CAD/CAM) machining ceramic Vita
      Mark II, this ability was affected by thickness and shade. METHODS: Each of 5
      specimens of 0.5 mm, 1.0 mm and 1.5 mm Vita Mark II A3C/18 and A2C/18 were
      prepared and the color change was measured after the substrate simulating stained
      teeth was covered with the specimen. RESULTS: Statistically significant
      differences (P < 0.01) were recorded in the substrates covered with different
      thickness and shade of Vita Mark II. The color changes (delta E) were 15.181,
      17.691, 19.667 and 15.653, 16.880, 18.002 after the substrates were covered with
      0.5 mm, 1.0 mm and 1.5 mm Vita Mark II A3C/18 and A2C/18. CONCLUSION: As a dental
      material, CAD/CAM Vita Mark II has high quality to mask the underlying color.
      Being a veneer, the masking ability with A2C/18 is better than that with A3C/18,
      but being an inlay, the result is reverse.

PMID- 14732981
TI  - [Reproducibility of centric relation of the patient with severe dental attrition
      for oral rehabilitation].
AB  - OBJECTIVE: Standards for determining mandibular position, especially the centric
      relation (CR), are in controversy because of anatomical, neurophysiological
      factors and research methods or instrument. The purpose of this study was to
      reevaluate the reproducibility of centric relation of the patients with severe
      dental attrition for oral rehabilitation. METHODS: Reproducibility of the centric
      relation of 6 patients with severe occlusal attrition was investigated by using
      D5A Denar fully adjustable articulator and the Pantronic recording system.
      RESULTS: 1. In supine position, anterior-posterior(AP) displacement of centric
      relation (CR) was 0.14 mm and superior-inferior(SI) displacements of CR were
      between 0.11 mm-0.12 mm. 2. In upright position, anterior-posterior displacement
      of CR was 0.35 mm and superior-inferior changes of CR were between 0.13 mm-0.20
      mm. CONCLUSION: The CR is the most stable and reproducible position of mandibule
      in normal stomatological system and is useful as a reference position in occlusal
      treatment and functional rehabilitation.

PMID- 14732982
TI  - [Clinical studies on apexification with demineralized dentin matrix].
AB  - OBJECTIVE: To study the clinical effects of demineralized dentin matrix (DDM) as
      a apexificating agent. METHODS: Human teeth were crushed into fragments and were
      deflated, demineralized, lyophilized to produce DDM. The DDM was used as an
      apexificating agent to treat 57 teeth compared with calcium hydroxide. X-ray film
      and clinical observation were undertaken after half a year, one year and two
      years. RESULTS: One year later, a barrier in the tooth apex was found in the X
      rays film. Then permanent filling material was used. After two years, DDM group
      had a healing rate of 92.86%, was higher than that of 91.30% in calcium hydroxide
      group, but there were no statistical significance. CONCLUSION: The findings
      suggest that DDM can be used as a new apexificating agent. One year after the
      apexification is the best opportunity to change the apexificating agent to a
      permanent root canal filling material.

PMID- 14732983
TI  - [The effect of Class III intermaxillary functional orthopedic force on the
      remodeling of pubescent rhesus monkeys' temporomandibular joint: an radiographic
      study].
AB  - OBJECTIVE: To study the effect of Class III intermaxillary functional orthopedic
      force on the remodeling of pubescent Rhesus monkeys' TMJ for different lengths of
      time. METHODS: Six pubescent Rhesus monkeys were divided into test group and
      control group. Monkeys in the test group wore TMAIII while the control group did
      not. Cephalometric technology and CT scanning were employed in this study.
      RESULTS: 1. Compared with the control groups, the cephalometric results showed
      that the relationship of the occlusion changed in the test groups. The growth of
      the maxilla was promoted and the development of the mandible was inhibited, but
      the mandibular length was not decreased. 2. Compared with the control groups, CT
      scanning results showed that the posterior space of TMJ in the test group
      narrowed and the anterior space widened. There was a statistical difference
      between the test group and the control group(P < 0.01), but no difference within
      the test group. CONCLUSION: Under Class III Orthopedic therapy, the occlusion
      relation was changed. The growth of maxilla was promoted and the development of
      mandible was inhibited. The posterior space of TMJ narrowed and the anterior
      space widened in test group.

PMID- 14732984
TI  - [Expression of constructed eukaryotic vectors carrying encoding gene of soluble
      human interleukin-1 receptor in mammalian cells].
AB  - OBJECTIVE: This study is to make sure if the constructed pcDNA3 carrying encoding
      gene of sIL-1R can be expressed in mammalian cells in vitro. METHODS: COS-1 cells
      and CHO cells were respectively transfected with recombinant plasmid pcDNA3/sIL
      1R by liposome. The protein expression products were detected by ELISA. RESULTS:
      The results indicated that the protein expression products could be detected in
      the cell plasma and the cell culture supermatant. The expression level in
      experimental groups was much higher than that in control groups(P < 0.05).
      CONCLUSION: The constructed pcDNA3/sIL-1R can express interest protein in
      mammalian cells and this establishes the basis for future investigation on gene
      therapy of periodonititis and other inflammatory diseases.

PMID- 14732985
TI  - [Study on tumor necrosis factor-alpha and interleukin 2 in rat skin allograft].
AB  - OBJECTIVE: To elucidate the histocompatibility of tissue engineered rat skin
      through studying the effect of TNF-alpha and IL-2 in immunological rejection
      after rat skin allograft. METHODS: Tissue engineered skin that the basic
      materials were taken from neonatal SD rats was cultured in lab, grafted to adult
      Wistar rats. The expressions of TNF-alpha and IL-2 in grafted tissue were
      detected with immunohistochemical staining and Western blot. RESULTS: The
      expressions of TNF-alpha and IL-2 were remarkable in skin allograft group, but
      low in tissue engineered skin group. CONCLUSION: The expressions of TNF-alpha and
      IL-2 and the immunological rejection were closely related after skin allograft,
      but the tissue engineered skin has favorable histocompatibility and doesn't arose
      obvious immunological rejections.

PMID- 14732986
TI  - [Experimental study of artificial bone composite of bicoral, rhBMP-2 and PLA in
      repairing calvarial defects].
AB  - OBJECTIVE: To study the effects of artificial bone composite of bicoral, rhBMP-2
      and PLA in repairing calvarial critical-size defects. METHODS: Calvarial defects
      in 24 rabbits were surgically made and then half of the defects were repaired
      with the artificial composite bone. Another half of them were repaired with
      bicoral/PLA composite and served as controls. Four rabbits in each group were
      sacrificed at 4, 8, 12 weeks after operation, respectively. The treatment effects
      were evaluated with scanning electron microscopy and mechanical strength testing.
      RESULTS: New bone was observed not only in the periphery, but also inside the
      artificial bone in both groups, but earlier and more new bone formation was
      observed in treatment group compared with control group. The mechanical strength
      test showed that the artificial bone in two groups, which had same mechanical
      strength before implantation, had significant different mechanical strength after
      operation. The strength of the artificial composite bone was higher than that of
      controls and was same with normal rabbit calvarial bone. CONCLUSION: The
      artificial composite bone possess a highly repairing ability, and the healing in
      bone defects may be accomplished by both osteoinductive and osteoconductive
      mechanism. The material may be used as a good substitute for bone grafting.

PMID- 14732988
TI  - [Regeneration in gaps of the middle-mountain moist evergreen broad-leaved forest
      of Ailao mountains].
AB  - On the basis of investigation on gaps in the middle-mountain moist evergreen
      broad-leaved forest of Ailao Mountains Natural Reserve, Yunnan Province, tree
      seedlings (H < or = 50 cm) composition were compared in the gaps and the non-gap
      stand. The results showed that the dominant tree species of the forest were not
      preponderated over others in the gaps. The composition of tree seedlings in the
      gaps differed from those in the non-gap stand. The species diversity of tree
      seedlings in the gaps(H = 2.73, D = 0.89) were higher than those in the non-gap
      stand (H = 2.25, D = 0.82), and the Jaccard correlative coefficient were only
      0.6. The density of tree seedlings in the gaps (38,636 N.hm-2) was much higher
      than that in the non-gap stand (17,323 N.hm-2), of which many species were only
      found in the gaps. The dominant height of the tree seedling in the gaps and the
      non-gap stand were also 11-20 cm, but the percentage of the tree seedlings higher
      than 20 cm in the gaps was significantly higher than that in the non-gap stand.
      The gap sizes had important impact on the tree seedling germination, and
      different species of tree seedling dominated in different size classes of gap.

PMID- 14732987
TI  - [The study of cucurbitacin BE polylactic acid nanoparticles delivering
      cucurbitacin BE to metastasized cervical lymph nodes in mice with oral cancer].
AB  - OBJECTIVE: The aim of this study was to investigate the delivery of Cucurbitacin
      BE to cervical lymph nodes by peri-cancer submucosal injection of the average
      diameter 85 nm Cucurbitacin BE polylactic acid nanoparticles (CuBE-PLA-NP).
      METHODS: Cervical lymph node metastasis model of mice oral cancer was established
      and CuBE-PLA-NP and CuBE were injected in peri-cancer submucosal of the mice
      respectively, the concentration in blood, heart, liver, spleen, lung, kidney and
      cervical lymph node were measured by high performance liquid chromatography at
      fifteen time points, Targeted cervical lymph nodes were evaluated by targeting
      index, selectivity index, targeting efficiency, relative targeting efficiency and
      ratio of maximum concentration. RESULTS: (1) The CuBE concentration in the
      cervical lymph nodes after CuBE-PLA-NP injection was far higher than that after
      CuBE injection at every time point, the CuBE duration in the cervical lymph nodes
      in CuBE-PLA-NP group was far longer than that in CuBE group; (2) The five
      targeted values of the cervical lymph nodes in CuBE-PLA-NP group was far higher
      than that in CuBE group; (3) The CuBE concentration in blood, heart, liver,
      spleen, lung and kidney in CuBE-PLA-NP group was far lower than that in CuBE
      group. CONCLUSION: The CuBE-PLA-NP can specifically deliver CuBE to the cervical
      lymph nodes by peri-cancer submucosal injection, increase CuBE concentration and
      duration in metastasized cervical lymph nodes, and decrease drug concentration of
      other organs.

PMID- 14732989
TI  - [Flora analysis of riparian plant communities on the northern slope of Changbai
      Mountain].
AB  - This study was conducted in the riparian forest of Erdaobaihe River, and the
      flora of riparian plant communities on the northern slope of Changbai Mountain
      was researched and analyzed. There were 288 vascular plant species belonging to
      169 genera and 68 families, among them, 26 plant species belonging to 16 genera
      and 11 families were fern, and 262 plant species belonging to 153 genera and 57
      families were spermatophyte. Among spermatophyte, there were 9 gymnosperm species
      belonging to 6 genera and 3 families and 253 angiosperm species belonging to 147
      genera and 54 families. Among angiosperm, there were 212 dicotyledonous species
      belonging to 118 genera and 45 families and 41 monocotyledonous species belonging
      to 29 genera and 9 families. All the results showed that there were abundant
      plant species in the riparian plant communities on the northern slope of Changbai
      Mountain. Analyses on the distribution area types of spermatophyte in the
      riparian communities showed that the distribution area types of genera and
      families were both abundant. For genus level, there were 9 distribution area
      types and 7 sub-types, and for family level, there were 6 distribution area types
      and 2 sub-types. The riparian plant communities had a temperate characteristic,
      and there were 117 genera, which were accounted for 76.5% of all the genera of
      spermatophyte, belonging to all the different temperate distribution types. In
      addition, the flora of riparian communities had a complex component, and had
      close relations with Tropical and East Asia distribution type, but few relations
      with Mediterranean distribution type. The results also showed that riparian zone
      could play an important role in biodiversity protection.

PMID- 14732990
TI  - [Hydraulic characters of Acer truncatum seedlings].
AB  - The hydraulic parameters of 4 years old Acer truncatum seedlings were measured by
      improved flushing method under the condition of controlled drought gradients in
      the greenhouse. It's indicated that the changes of hydraulic parameters with stem
      segment functional xylem diameter could be modeled by different equations. The
      hydraulic conductivity was influenced by the area that stem segment located. It
      was higher in non-constriction area than in constriction area. The existence of
      constriction area was in favor of the competition between individual seedlings.
      Hydraulic conductivity, specific conductivity and leaf specific conductivity were
      proportional with functional xylem diameter and twig water potential. The leaf
      specific conductivity of thicker branches was far higher than that of distal
      twigs, which was in favor of seedlings in saving those organs with more
      photosynthesis devotion during drought stress. The change of Huber value of same
      diameter branches with twig water potential was very small before defoliation,
      and hence, the main source of seedling's water stress came from xylem cavitation
      and embolism.

PMID- 14732991
TI  - [A comparative study on seed germination of 15 grass species in Keeqin
      Sandyland].
AB  - A laboratory study was made on the germination characteristics of freshly
      collected seeds of grass species at the Wulanaodu area of Keeqin Sandyland in
      Eastern Inner-Mongolia. Of the 15 species examined, 8 species including
      Clinelymus dahuricus, Cleistogenes squarrosa, Pappophorum boreale, Spodiopogon
      sibiricus, Phragmites communis, Chloris virgata, Arundinella hirta, Pennisetum
      alopecuroides had a germination rate of over 80%, but 4 species including
      Echinochloa hispidula, Hemarthria compressa, Tragus berteronianus and Setaria
      viridis had a value of less than 10%. Spodiopogon sibiricus, Eragrostis pilosa,
      Phragmites communis, Chloris virgata, Clinelymus dahuricus, Pappophorum boreale,
      Digitaria cilliaris and Cleistogenes squrrosa began to germinate within 1-3 days
      after the test began, while Setaria viridis, Tragus berteronianus and Hemarthria
      compressa failed to germinate in a period of more than 10 days. For the species
      such as Digitaria cilliaris, Echinochloa hispidula, Phragmites communis,
      Eragrostis pilosa and Spodiopogon sibiricus, their germination period was less
      than 10 days, while Clinelymus dahuricus and Pappophorum boreale had a
      germination period of more than 20 days. The days required for half the final
      germination rate to be reached were: 2 days for Chloris virgata, 3 days for
      Phragmites communis, 4 days for Spodiopogon sibiricus, 5 days for Clinelymus
      dahuricus and Cleistogenes squarrosa, 7 days for Arundinella hirta and
      Pappophorum boreale, and 10 days for Pennisetum alopecuriodes. Compared with the
      Sheffield region in Britain, the Wulanaodu area of Kerqin Sandyland had a higher
      proportion of annul grasses with a low germination rate and a longer germination
      period, and the perennial grasses at the Wulanaodu area had an approximately same
      germination rate, but a longer germination period. During germination, ruderals
      showed the potential for risk-sharring, and thus, they had a relatively higher
      disturbance-resistance capacity.

PMID- 14732992
TI  - [Gap edge effect of Castanopsis kawakamii community].
AB  - This paper reported the characters of gap edge effect of Castanopsis kawakamii
      community in Sanming, Fujian Province. The species diversity, ecological
      dominance, and edge effect strength of 38 forest gaps with different development
      stages in different stands of Castanopsis kawakamii community were measured, and
      Shannon-Wiener index, Simpson index, and index of edge effect strength were
      calculated. The results showed that the index of the gap edge effect of
      Castanopsis kawakamii community was about 0.7-1.3 (according to the species
      diversity index) and 0.3-1.8 (according to the ecological dominance index). The
      gap edge effect had the trend of increasing the species diversity of forest
      communities. The index of gap effect was affected by the size and development
      stage of the gap and the related forest type. The study provided a theoretical
      basis for the maintenance of species diversity and the forest management in
      Castanopsis kawakamii community.

PMID- 14732993
TI  - [Population dynamics of Quercus variabilis on northern slope of Qinling
      mountains].
AB  - Studies on the population dynamics, age structure, spatial distribution pattern,
      life table, and survival curve of Quercus variabilis showed that the Q.
      variabilis population on the northern slope of Qinling mountains was increasing.
      The number of young-aged individuals was larger, and that of middle-aged and old
      individuals was smaller. The life tables for different age classes showed that
      the mortality at age classes I and II was the highest, and the mortality rate was
      decreased with increasing age. However, at age classes VII and VIII, the
      mortality rose again for their decrepitude. The expected life span of age classes
      III, IV and V was higher, and decreased gradually with increasing age. The
      survival curves were the type of Deevey III, and the distribution pattern of
      population was aggregative as a whole. As the age increased, the intensity of
      aggregation decreased, and tended to a random distribution at higher elevations.
      A wise management should accelerate the recovery of Q. variabilis population and
      the enhancement of its productivity. The altitude 800-1,100 m was the favorable
      habitat for Q. variabilis population. As for the Q. variabilis at lower altitude,
      its protection should be reinforced, and the disturbance from human beings should
      be reduced. Forest thinning and other fostering management at middle altitude
      should be given in time. The target trees at higher altitude should be fostered.

PMID- 14732994
TI  - [Evaluation on sustainability of forest resources in Bailong River forest region,
      Gansu Province].
AB  - Based on the theories of sustainable development of forest resources, this paper
      constructed an index system for the integrative evaluation on the sustainability
      of forest resources in Bailon River forest region of Gansu Province. After
      calculated the index values of five strategic levels and twenty measure levels,
      the degree of harmony (DH) was obtained, with which, the sustainability of test
      forest resources could be evaluated. The DH value was 0.5320 in 1996 and 0.6100
      in 2000, which was smaller than the theoretic value of 0.7000, and hence, this
      forest region belonged to non-sustainable development, but made some progress for
      its sustainability.

PMID- 14732995
TI  - [Ecological restoration effects of typical manmade ecosystems and relationships
      between restoration variables in middle Yunnan area].
AB  - This paper studied the restoration effects of Pinus yunnanensis forest, mixed
      Eucalyptus maideni-Acacia meamsii forest, Eucalyptus maideni forest and restored
      natural vegetation in middle Yunnan area. The man-made forests consisting of
      different tree species had different effects on plant diversity, forest
      hydrology, soil surface erosion control, soil amelioration, and forest
      characteristics. Afforestation with native species promoted the plant diversity.
      Recovery Distance Index(RDI) was calculated for the evaluation of the forest
      restoration extent based on Principal Component Analysis (PCA). The restored
      natural vegetation P. yunnanensis forest, E. maideni forest, and A. mearnsii-E.
      maidensi forest would need correspondingly 29.14, 14.36, 34.23, and 11.03 years
      to recover to the ecological functions of zonal climax community. There were some
      relationships among forest recovery variables. Shannon-Wiener index, herbage
      coverage, community evenness, species diversity, soil available K, soil bulk
      density, biomass of herbage, woody plant coverage, timber volume of woody plant,
      soil total K, soil erosion, soil Si/V, littersfall, soil non-capillary porosity
      and through-fall were the main variables among the forest restoration variable
      dealt with in our work. Diversity played a central role in the restoration of
      ecosystem structure and functions.

PMID- 14732996
TI  - [Eco-physiological responses of Picea mongolica ecotypes to drought stress].
AB  - The seedlings of different Picea mongolica ecotypes were treated with drought
      stress, and their height growth, MDA, proline, and chlorophyll content were
      investigated. The results showed that the height growth was obviously reduced by
      drought stress. With sufficient water supply, the height growth of f. viridis W.
      D. Xu f. nov Picea mongolica was rapid and obviously better than that of f.
      purpurea W. D. Xu f. nov Picea mongolica, but was obviously reduced by intense
      drought stress. Furthermore, drought stress shortened the annual growth period of
      Picea mongolica, and made its terminal bud formation more than one month earlier
      increased in both needles and roots, but was higher in needle than in root. The
      MDA content was higher in Picea mongolica than in f. viridis W. D. Xu f. nov
      Piburcea mongolica, and the proline content in needles was increased with
      increasing drought stress, but in roots, the proline content was higher in f.
      viridis W. D. Xu f. nov Picea mongolica than in f. purpurea W. D. Xu f. nov Picea
      mongolica and f. rubra W. D. Xu f. nov Picea mongolica. The latter 2 forms showed
      a similar trend in chlorophyll content. Their chlorophyll a, chlorophyll b and
      total chlorophyll contents increased at the beginning of drought treatment, and
      then decreased with increasing drought stress. The chlorophyll content of f.
      viridis W. D. Xu f. nov Picea mongolica decreased with drought stress. The ratio
      of chlorophyll a/b decreased from maximum to minimum in f. viridis W. D. Xu f.
      nov Picea mongolica, but decreased in a relative small extent in f. purpurea W.
      D. Xu f. nov. It's proved that f. purpurea W. D. Xu f. nov Picea mongolica had a
      larger drought-resistance capacity than f. viridis W. D. Xu f. nov, and f. rubra
      W. D. Xu f. nov was a typical transitional ecotype from f. purpurea W. D. Xu f.
      nov to f. viridis W. D. Xu f. nov.

PMID- 14732997
TI  - [Succession pattern of artificial vegetation community and its ecological
      mechanism in an arid desert region].
AB  - Focusing on the artificial vegetation protection system of the Shapotou section
      of Baotou-Lanzhou railway in the arid desert region of China, this paper examined
      the dynamics of dominant plant species and the succession pattern of artificial
      plant community in the process of establishing and developing regional artificial
      vegetation. It also studied the driving force and the ecologically intrinsic
      mechanism of the community succession. The results demonstrated that the species
      composition of the artificial vegetation dramatically changed after 40 years of
      succession, from original artificial plant community of shrub and semi-shrub to
      artificial-natural desert plant community with annual herb dominated. During the
      process of succession, the importance values of artificial shrubs, such as
      Caragana korshinskii and Hedysarum scoparius, decreased and gradually retreated
      from the artificial plant community, while the naturally multiplied annual herb,
      such as Eragrostis poaeoides, Bassia dasyphylla, Salsola ruthenica, Chloris
      virgata and etc., were presented one after another and gradually became dominant.
      Besides, Artemisia ordosica always played a key role in the community due to its
      ability of naturally sowing and self-replacement. This type of succession pattern
      was closely related to the shortage of precipitation resource in this region and
      the formation of soil crust which inhibited the reproduction of shrub and
      perennial herb with deep root systems. This study provided a theoretical ground
      for realizing persistent development of artificial plant community.

PMID- 14732998
TI  - [Soil seed banks of different grassland types of Alashan arid desert region,
      Inner Mongolia].
AB  - Investigations on the soil seed banks of different grassland types of Alashan
      arid desert region in Inner Mongolia showed that when the altitudes of sampling
      plots increased from 1,370 m to 1,750 m, the soil seed densities of natural
      grasslands decreased from 326 grain.m-2 to 76 grain.m-2. At the altitude of 1,100
      m, the soil seed density was 56 grain.m-2 in typical desert plot, but only 8
      grain.m-2 in the sand dune plot. After the vegetation was restored with Artemisa
      sphaerocephala on sand dune, its soil seed density increased obviously, almost as
      17-29 times as sand dune's. In this study, 31 seeds m-2 were sampled, which
      belonged to 11 families. Among them, annual plants accounted for 77%, 100% and
      70%, perennial plants accounted for 21%, 0 and 16%, and semi-shrubs accounted for
      2%, 0 and 14%, respectively for natural grassland, sand dune and sown grassland.
      Shrub seeds were not found in all the soil seed bank plots. When the altitudes of
      sampling plots increased from 1,100 m to 1,750 m, the species richness (Margalet
      index) of soil seed banks of natural grasslands increased from 1.49 to 2.77, and
      the species diversity (Shannon-Winner index) increased from 0.697 to 0.917.

PMID- 14732999
TI  - [Landscape structure and ecological coupling analysis of ecotone on the west
      Sonnen Plain].
AB  - Ecotone is a special zone in the landscape, which is very susceptive to the
      changes in environmental conditions, and hence, is prone to the disturbance by
      unfavorable conditions. Human activity has a series of positive and negative
      effects on it, and greatly changes the geo-chemical process in the ecosystem. In
      the ecosystem, especially in the ecotone, different systems and regimes are
      interconnected and inter-determined. For the sustainable development of ecosystem
      and the protection and rational utilization of resources, it is of great
      importance to study this internal relationship and to seek rational regulation
      and control measures. With the ecotone in the west Songnen Plain as an example,
      and based on the studies of the topography, physiognomy, soil, vegetation, and
      their geographic distribution in the ecotone., this paper explained the structure
      of the ecological landscape, and quantitatively analyzed the ecological geo
      chemical processes under different landscape conditions. In addition, this paper
      also tried to make coupling analyses to the ecologic succession and the landscape
      geo-chemical environment. Under current conditions, the succession of plant
      communities and the shift of soil landscape geo-chemical conditions in the west
      Songnen Plain are almost co-instantaneous, and these two factors can inter
      determined under certain conditions.

PMID- 14733000
TI  - [Dynamics of atmospheric delta 13C in the past 440 years in Aleitai, Xinjiang].
AB  - Since industrial revolution, a large amount of anthropogenic CO2 from fossil fuel
      combustion and deforestation has been emitted into atmosphere, and thus, the
      atmospheric CO2 concentration increased rapidly, while the delta 13C in
      atmospheric CO2 became lower and lower due to Suess effect. Therefore, the
      prediction of delta 13C is crucial for studying global changes. In order to make
      an accurate prediction, it is necessary to understand its historical variation.
      The dynamics of delta 13C in plants can sensitively reflect it. In this paper,
      the dynamics of delta 13C in atmospheric CO2 in the past 440 years in Aleitai,
      Xinjiang were reconstructed by using tree-ring delta 13C series and plant stable
      carbon isotope fractionation model. The results showed that atmospheric delta 13C
      value was relatively constant before 1,850 (R2 = 0.052), which was about 
      6.60@1000, while a sharp decrease in atmospheric delta 13C with an average of 
      7.02@1000 was found since 1,850 (R2 = 0.65). Compared with those from ice core
      bubbles, more fluctuations were found in atmospheric delta 13C derived from tree
      ring series, possibly due to the higher resolution of the latter, and the
      difference of real atmospheric delta 13C between the growth site of the tree and
      the globe.

PMID- 14733001
TI  - [Application of ISSR technology in genetic diversity detection of jute].
AB  - The genetic diversity among 27 accessions of Corchorus, including 10 Jute
      species, was investigated with ISSR technique. 283 DNA bands were amplified with
      25 ISSR primers, among which, 263 (92.85%) were polymorphic, with 10.48 bands per
      primer in average. A further systemic cluster analysis indicated that the
      accessions could be clustered into three groups, and the group II (including two
      cultispecies and their close wild species) was obviously genetically different
      from the groups I and III (including eight wild species). Moreover, 16 accessions
      in group II presented a higher intraspecific genetic resemblance, while 11
      accessions among groups I & III showed an abundant interspecific genetic
      diversity. After synthesized the relevant findings of morphology and DNA
      classification, it's found that C. urticifolius could be one of the original wild
      species, C. tilaculariszic was a variation of C. tilaculari, and Tian Jute could
      be an untitled wild species.

PMID- 14733002
TI  - [Interrelationship between water use efficiency and nitrogen use efficiency of
      different wheat evolution materials].
AB  - A field micro-plot experiment on the interrelationship between water use
      efficiency and nitrogen use efficiency of different wheat evolution materials at
      the whole plant level showed that both water and nitrogen use efficiency
      increased gradually during the long evolution process from diploid to hexaploid.
      The water use efficiency was positively related with nitrogen use efficiency
      across nine evolution materials excluding French S. cereals, suggesting that the
      high nitrogen use efficiency of French S. cereals might be related with
      physiological mechanisms other than WUE.

PMID- 14733003
TI  - [Niches analysis of three aphid populations on spring sowing maize].
AB  - Systematic analysis of aphid populations and niches patterns on spring sowing
      maize was carried out during 1998-1999 in the suburbs of Chongqing. The results
      indicated that there were three aphid populations Rhopalosiphum maidis Fitch.,
      Rhopalosiphum padi Linn. and Sitobion avenae Fabricius distributed on the spring
      sowing maize. The mixed aphid populations traded off during the growth period of
      spring sowing maize, and two peaks of quantitative counts were shown at the mid
      and last ten days of May and the last ten days of June. In addition, the niches
      of aphid population were also discussed from one dimension (i.e., temporal or
      spatial) to two dimensions (i.e., temporal and spatial). Through the quantitative
      analysis of niche breadth and niche overlap, the highly temporal differentiation
      of M. avenae and the highly gathering character of R. maidis were all indicated.
      R. padi showed an indistinct differentiation, while R. maidi was a dominated
      population on the spring sowing maize.

PMID- 14733004
TI  - [Three-dimentional distribution pattern dynamics of Erythroneura sudra and its
      natural enemy Erigonidum graminicola].
AB  - Investigations on the Erythroneura sudra and Erigonidum graminicola populations
      in three layers (upper, middle and lower) and four directions (east, south, west
      and north) of peach tree crown showed that both of them had aggregated spatial
      distributions in these 7 part, because 5 parameters used to analyze the
      distribution reached required standard. Each insect was attracted by the others,
      as the parameter (alpha) in Iwao formulation m* = alpha + beta x - (1971) was
      positive. The average density of aggregation was the biggest in its middle layer
      and east direction, and the smallest in its lower layer and south direction. The
      biggest average density of aggregation appeared in mid-September.

PMID- 14733005
TI  - [Soil organic carbon pool and its spatial distribution pattern in the Circum
      Bohai Region].
AB  - The research and management of soil carbon pool and the effect of land-use on it
      are the key project of study on global change. In this paper, the data of 1,374
      soil profiles in the Circum Bohai Region were used to estimate the soil organic
      carbon (SOC) pool of this region. The results showed that in this region, the
      total soil organic carbon pool in 1 m depth was 2.1 Pg C, and the biggest SOC
      pool was brown soil, occupying 55.6% of the total SOC. The second one was
      moisture soil, accounted for 26.9%. The SOC pools of aeolian sandy soil and dark
      brown soil were very small, only about 0.1% of the total. However, the soil
      organic carbon density (OCD) of boggy soil was the biggest (22.90 kg C.m-2), the
      second was dark brown soil (16.04 kg C.m2), and the lowest were aeolian sandy
      soil (2.88 kg C.m-2) and solonchak (6.0 kg C.m-2), implying that desertification
      and salinalization could reduce soil organic carbon. Moreover, the results also
      suggested that the topsoil held 673.30 Tg C. It meant that there was about one
      third of the total SOC could be easy to be disturbed. According to the OCD at its
      level distribution gradient, it could be divided into four regions, i.e., coastal
      region, plain region, northwestern region, and hilly region. The order of OCD
      from high to low was hilly region, northwestern region, plain region, and coastal
      region. This regulation reflected not only the role of climate and landform, but
      also the effect of human activity intensification on SOC. Therefore, it was very
      important to protect and manage the land in this region well for the SOC
      maintenance and the sustainable land use.

PMID- 14733006
TI  - [Spatial distribution characteristics and ecological effects of carbon and
      nitrogen of soil in Huolin River catchment wetland].
AB  - This paper studied the spatial distribution characteristics and ecological
      effects of organic carbon and nitrogen in soils of Huolin River catchment wetland
      in horizontal and vertical levels. The results showed that the differences of
      horizontal and vertical distribution of organic carbon and nitrogen were very
      obvious, and of all the factors such as the period of wetting and drying cycles,
      leaching, plant and flood etc., the period of wetting and drying cycles was
      contents the critical one, which caused the differences. Soil organic carbon was
      significantly correlated with soil nitrogen (r = 0.977). The ratio of carbon and
      nitrogen (C/N) changed along with the humidity gradient, and soil pH values
      obviously influenced the concentration of organic carbon and nitrogen. The
      correlation of C/N values and organic carbon and nitrogen contents in wetland
      soil and in grassland soil were remarkably different, and the ecological effects
      mainly included production effect and clarification effect.

PMID- 14733007
TI  - [Reserves and spatial distribution characteristics of soil organic carbon in
      Guangdong Province].
AB  - Soil organic carbon is the main part of terrestrial carbon reservoir and
      important part of soil fertility. The spatial distribution and reserves of soil
      organic carbon are very important for studying soil carbon cycle. According to
      the data from the second soil survey, soil organic carbon reserves was estimated
      and its spatial distribution was analysed by using GIS technique. The results
      showed that the total amount of soil organic carbon is about 17.52 x 10(8) t. The
      carbon density of laterite, lateritic red soil and red soil in Guangdong Province
      is 8.83, 10.31, 9.15 kg.m-2, respectively; lower than the mean carbon density of
      China. The carbon density of yellow soil and rice soil is 12.08, 12.17 kg.m-2,
      respectively; higher than the mean carbon density of China. Soil carbon density
      is about 10.44 kg.m-2 in Guangdong. The spatial distribution characteristic of
      soil organic carbon density in Guangdong is that the carbon density in south
      Guangdong Province is higher than that in north Guangdong Province, in that soil
      organic carbon density in north and middle Guangdong Province is 5-10 kg.m-2 and
      in east Guangdong Province is 10-15 kg.m-2. Soil organic carbon density mostly
      vary among 5-15 kg.m-2.

PMID- 14733008
TI  - [Effect of nitrogen nutrition on endogenous hormone content of maize under soil
      drought conditions].
AB  - It is realized in recent years that roots play an important role in the control
      of shoot growth and development, not only because they can continuously provide
      the shoot with water and nutrients, but also because some chemical messengers are
      produced in roots to response soil drought stress and transported through
      transpiration stream to shoot where physiological processes are regulated.
      Extensive studies showed that the decrease of leaf conductance was closely
      related to the increase of xylem ABA concentration, suggesting that ABA can act
      as a water stress signal to regulate the physiological response of shoot.
      Fertilizer plays an important role in increasing crop yield and water use
      efficiency (WUE) on dry-land farming. It is not clear, however, whether the
      application of N fertilizer can affect the root's signal intensity in drought
      stress and thus regulate its stomatal responses. Experiment with 3 water levels
      (35%, 55% [symbol: see text] 75% +/- 5% of field capacity) and 2 N fertilizer
      levels (high N and low N) was designed to investigate the effect of soil drought
      and N nutrition on endogenous hormone concentration (ABA and ZRs) and stomatal
      conductivity of maize under potted conditions. The results showed that the
      application of N significantly increased the stomatal conductivity of maize leaf
      under both drought and watered conditions. Meanwhile, it markedly decreased the
      ABA concentration in root xylem sap, but increased ABA concentration in leaf of
      maize under soil drought conditions. The application of N decreased ZRs
      concentration in root xylem sap as well, which means that ZRs did not play a role
      in counteractive to ABA under soil drought conditions. The lower ABA
      concentration in root xylem sap of high N maize rather than the higher ABA
      concentration in maize leaf accounted for the higher stomatal conductivity of
      high N maize leaf under soil drought conditions.

PMID- 14733009
TI  - [Parameters of energy flow in wheat-corn intercropping agroecosystem].
AB  - The parameters of energy flow of primary producers (agricultural crop and weed),
      consumers (pests and their natural enemies) and decomposer (soil microbe,
      protozoan and saprozoite) in wheat-corn intercropping agroecosystem in Tibet of
      China were studied by field investigation and laboratory measurement. The results
      showed that the wheat-corn intercropping agroecosystem had high primary
      productivity and energy translation efficiency, and the degression rate of energy
      flow through food chain was also high. At each nutritive layer of this
      agroecosystem, relatively less energy was required to product unit energy, and
      degree of energy utilization of superior nutritive layer from lower nutritive
      layer was increased gradually.

PMID- 14733010
TI  - [Effect of plastic film mulching on soil microbial biomass in spring wheat field
      in semi-arid loess area].
AB  - This paper studied the effect of different periods of plastic film mulching (M0
      no mulching, M30-mulching for 30 days, M60-mulching for 60 days, and M-mulching
      for whole growth period) on soil microbial biomass carbon (SMBC) of spring wheat
      field in semi-arid loess plateau. The mean SMBC in 1999 and 2000 was 335.3 and
      259.3 mg.kg-1 dry soil, respectively. It was 29.3% higher in 1999 than in 2000.
      The highest SMBC was recorded at the harvest stage in M treatment for the two
      years. In 1999, a wet year with more rainfall, the SMBC of M60 and M treatments
      was significantly higher than those of M0 and M30 in the mid-period of growth,
      reached its top at the end of the growth period. The highest grain yield was also
      achieved in M60. It was a dry year in 2000, but rainfall was rich in the latter
      growth period of spring wheat. SMBC increased at the beginning period of growth,
      and did not increase during the mid-growth period. It increased again during the
      latter period of growth, and showed a significant difference among the
      treatments. At the harvest stage of 2000, SMBC in M0 was the highest among all
      the treatments. It was similar between M and M60, and lower than that of M30. In
      the two years, the ratio of C/N ranged between 7.732-9.042, being lower than the
      threshold of 11.3, and the ratio of C/P was 300.8-719.6, being higher than the
      threshold of 300. The two parameters showed that the increase of SMBC was
      inhibited because of the competition of soil available nutrients between soil
      microbes and crops. These indicated that soil organic matter content was so
      shortage that it became the key factor to restrict crop productivity. Under this
      condition, increasing crop productivity through the input of chemical fertilizers
      would conceal the problem of soil degradation, and result in a further decrease
      of soil quality. A long term plastic film mulching would make the problem more
      serious.

PMID- 14733011
TI  - [Effect of Sinorhizobium fredii YC4 symbiotic plasmid amplification on nod
      factors and symbiotic N-fixation].
AB  - Sinorhizobium fredii YC4 can form nitrogen-fixing nodules on soybean (Glycine
      max) and wild soybean (G. soja). It can produce unique lipochitooligosaccharide
      nod factors (LCOs), in comparison with the other four strains of S. fredii. The
      constitution of LCOs produced by YC4 contained more hydrophobic substitutions
      detected by Thin-layer chromatography (TLC) of 14C-labeled nod factors. A
      spontaneous mutant termed YSC3 amplified in the symbiotic plasmid was isolated
      from YC4, which can produce more amount of LCOs than its parental strain at 28
      degrees C, and showed a difference in the construction of LCOs. Nodulation test
      indicated that YSC3 only formed ineffective nodules on soybean G. soja.

PMID- 14733012
TI  - [Identification on an antagonistic rhizobacterium X3 from rhizosphere of
      cucumber].
AB  - Classical physiological and biochemical methods, Biolog, and 16S rDNA analysis
      were used to identify the strain X3 which could control cucumber seedling damping
      off. Physiological and biochemical identification showed that it belonged to
      Pseudomanas aeruginosa, but Biolog identification showed it was P. spinosa. 16S
      rDNA determination and analysis was used for further identification, which showed
      that the 16S rDNA sequence of X3 shared 93.7% homologies with published sequence
      of P. aeruginosa from GenBank, and both sequences constituted a branch in
      Phylogenetic tree. Based on these results, it is considered that the strain X3
      belongs to one strain of P. aeruginosa.

PMID- 14733013
TI  - [Effect of environmental factors on the growth and fatty acid composition of five
      endophytic fungi from Sapium sebiferum].
AB  - Five fungi species including Rhizoctonia sp., Sclerotium sp., Acremoniell sp.,
      Chaetomium sp. and Pestalotiopsis sp. screened from the inner bark of Sapium
      sebiferum (Level) Roxb. were used to study their growth under different
      environmental factors, with the biomass and fatty acid composition as main
      indexes to elucidate the relationship between plant and its endophytic fungi.
      Compared with that from synthesized medium, a higher biomass was harvested when
      the fungi were cultured on liquid potato dextrose medium; the unsaturation index
      of fatty acid (IUFA) was lower, and the main fatty acids in the fungi were
      linoleic acid, palmitic acid and oleic acid. Compared with the fungi grown on the
      synthesized medium without Sapium sebiferum's extract, the Sclerotium sp. growth
      was promoted, and the others were inhibited when the extract was added to the
      synthesized medium. At the same time, the IUFA were increased. When 0-1.0 mol.L-1
      NaCl was added in Sclerotium sp.'s culture medium, the biomass was not changed
      notably; IUFA in 0-0.5 mol.L-1 NaCl was not significantly different, while in the
      range of 0.6-1.0 mol.L-1 NaCl, the IUFA was decreased with increasing
      concentration of NaCl. It indicated that fungus had a stronger tolerance to salt.
      Sclerotium sp.'s growth was promoted, and the IUFA was increased when plant oil
      was added in the synthesized medium. The biomass was the highest by adding 1.5%
      plant oil. The results mentioned above were some way related to the symbiotic
      relations between the endophytic fungi and their host plant.

PMID- 14733015
TI  - [Optimum soil water supply range of Malus pumila].
AB  - By means of the determination of net photosynthetic rate and transpiration rate
      of the leaves of seven-year field and two-year spotted Malus pumila (Goldspur)
      under different soil water contents and illumination and calculation of water use
      efficiency (WUE), the optimum soil water supply range of Malus pumila was
      determined. The results showed that because photosynthetic advantageous radiation
      (PAR) and soil water content (SWC) decided the value of photosynthetic rate and
      transpiration rate of Goldspur, thus they influenced the value of WUE. The
      response of WUE to illumination had relations with soil water. When SWC was 10%
      (50% of field capacity-FC) or so, the maximum of WUE was the highest value among
      all the soil water treatment and reached about 230 mumolCO2.g-1H2O. When the
      water supply was adequate (SWC > 15%), the maximum was only 160 mumolCO2.g-1H2O
      or so, the difference between each SWC level was not obvious and simulated curve
      fundamentally overlapped, although WUE decreased slowly after reached the
      maximum. The variation of WUE with SWC had relations with illumination. WUE was
      the highest while PAR was in the range of 500-1,000 mumol.m-2.s-1). Because the
      state of soil water decided the values of stomatic resistance (RS) and leaf water
      potential, RS and psi 1 also had influence on the changes of WUE. When RS and psi
      1 were respectively 2.0 s.cm-1 and -3.0 MPa, WUE was the highest, but Pn was
      relatively low, which was not good to the normal growth and fruitage of trees.
      From the overall consideration of WUE, Pn and Tr, the scopes of RS and psi 1 were
      2-6 s.cm-1 and -2.1 approximately -1.65 MPa, respectively, which not only
      guaranteed the normal photosynthesis of Goldspur, but also benefited the increase
      of WUE. The scope of the corresponding SWC was 11%-15%, which was equal to 55%
      75% of FC and this scope could be used as theoretical index of field water supply
      for Goldspur.

PMID- 14733014
TI  - [Effect of enhanced ammonium nutrition on photosynthesis and nitrate reductase
      and glutamine synthetase activities of winter wheat].
AB  - A controlled hydroponics experiment was conducted to investigate the effects of
      three NH4+/NO3- ratios (0/100, 50/50 and 100/0) on the photosynthesis and the key
      nitrogen metabolism enzymes of three wheat cultivars with different sensitivity
      to enhanced ammonium nutrition (EAN). Compared with NO3- alone, EAN significantly
      increased the leaf chlorophyll content, net photosynthetic rate, and soluble
      sugar content. It also significantly increased the soluble protein content in
      leaves and roots and the nitrate reductase activity in leaves, but had no
      significant effect on Glutamine synthetase (GS) activity. EAN increased the
      soluble sugar content in leaves, and correspondingly, enhanced the net
      photosynthetic rate and maintained a higher soluble sugar/protein in leaves and
      roots, which was favorable to the nitrogen assimilation and plant growth.

PMID- 14733016
TI  - [Reproductive biology of Macrobrachium nipponensis in Lake Wuhu].
AB  - Macrobrachium nipponensis is a key species of freshwater shrimps in China. To
      know its reproductive biology is very important for its protection and rational
      use. Studies from September 1998 to September 1999 in LakeWuhu showed that the
      spawning ground of M. nipponensis was situated in the littoral zone of the whole
      lake. The main spawning period of overwintering shrimps was from mid-April to mid
      July (water temperature 20.5-31 degrees C), and that of non-overwintering shrimps
      was from mid-July to mid-September (water temperature 31-23 degrees C). The sex
      ratio (female:male) increased gradually during the spawning period, and the
      absolute fecundity of overwintering shrimps was higher than that of non
      overwintering ones. The relationship between absolute fecundity and body length
      and between absolute fecundity and body weight could be expressed as cubic
      equation and simple linear equation, respectively. The relative fecundity (RW) of
      M. nipponnensis could regard as a constant, and its 95% confidence limits was
      1067.76 +/- 16.94 eggs.g-1.

PMID- 14733017
TI  - [Dynamics of dry deposition velocities (Vd) of atmospheric SO2 on rapeseed/rice
      rotation systems in selected area of south China].
AB  - With the profile meteorological data collected from the farmland micro
      meteorological experimental substation, Experiment Station of Red Earth Ecology,
      Yingtan, Jiangxi, Chinese Academy of Sciences during rapeseed/rice rotation from
      Nov. 1998 to Oct. 1999, the surface layer turbulence characteristic parameters
      (u*, theta*, L) and the atmospheric SO2 dry deposition velocities (Vd) were
      calculated. The results indicated that the hourly mean Vd of SO2 dry deposition
      was ranged from 0.124 to 0.897 cm.s-1 (mean +/- SE = 0.507 +/- 0.167 cm.s-1), and
      its regular dynamic pattern was as follows: it was always higher at daytime than
      at night, and the mean Vd of SO2 dry deposition during March-August(0.611 cm.s-1)
      was obviously greater than that during Sept.-Dec. and Jan.-Feb. (0.401 cm.s-1).
      The mean Vd of SO2 dry deposition during various crop growth stages was decreased
      as the order of rice (0.605 +/- 0.093 cm.s-1) > rapeseed (0.491 +/- 0.166 cm.s-1)
      > follow (0.342 +/- 0.174 cm.s-1).

PMID- 14733018
TI  - [Effects of simulated acid rains on Cd, Cu and Zn release and their form
      transformation in polluted soils].
AB  - The release and form transformation of Cd, Cu, and Zn in polluted red soil and
      yellow red soil affected by simulated acid rains were studied through batch
      equilibrium experiments. The results showed that the release of test heavy metals
      increased significantly with decreasing pH value of simulated acid rain. Their
      release amount was negatively correlated to the pH value of acid rains. In
      polluted red soil and yellow red soil, Cd existed mainly in exchangeable form,
      and Cu in organically bound and Mn oxide-occluded forms. Zn existed mainly in
      residual and exchangeable forms in polluted red soil, and in residual and
      organically bound forms in polluted yellow red soil. To some extents, the release
      of Cd, Cu and Zn and the chemical forms of Cd and Zn in test soils were affected
      by soil organic matter content and CEC. The release amount of bio-available Cd
      and Cu in polluted red soil and yellow red soil was increased greatly with the
      increasing acidity of simulated acid rains, but the transformation of Zn from
      stable to bio-available form was not obvious.

PMID- 14733019
TI  - [Several problems in ecological security assessment research].
AB  - Ecological security assessment is the identification and judgment of ecosystem
      completeness and sustainable ability to maintain ecosystem health under all kinds
      of risks, the core contents of which are ecological risk assessment and
      ecological health assessment. Ecological risk identification and ecological
      vulnerability are the composing elements of ecological risk assessment, while
      ecological health includes three aspects, i.e., ecological completeness,
      ecosystem vigor, and ecosystem resilience. In the studies of ecological security
      assessment, the rational combination of ecological risk and ecological health,
      and the establishment of integrated measure index system based on confirming
      spatial scale are needed. At present, risk factor identification index, exposure
      analysis index, and influence (response) analysis index are the broader
      construction systems of ecological risk index. Nevertheless, on the basis of the
      classification of EDI, REI and IRI, the method of superimposing exposure analysis
      index may be the development direction of establishing index system in the
      future. Among the methods of quantificational assessment, exposure-response
      analysis was one of the most extensive method used at present, but ecological
      model method to assess different-scale ecological security will be the main
      development field, and focused on the security of ecological processes in the
      future. Ecological security assessment must be intergraded with ecological
      prediction, security guarantee and management.

PMID- 14733020
TI  - [Application of mist net in studies of forest bird communities].
AB  - It had been more than twenty years for using mist net to study forest avian
      community. Mist net was very useful for studying cryptic, less vocal or non
      vocal, and non-territorial birds, particularly understory birds in forest. The
      accuracy of mist net was relatively independent of observer biases and skills. It
      allowed identical and simultaneous sampling of numerous sites and straightforward
      comparisons among studies done at different sites by different people. So, a lot
      of ornithologists considered it as a necessary way for studying forest bird
      communities. Few studies had been reported on bird communities by using mist nets
      in China. In this paper, some examples on studying forest bird community by using
      mist nets were introduced, and studies on forest bird community with mist net
      should be used widely in China in the future.

PMID- 14733021
TI  - [Ecological protection of medicinal woody plants].
AB  - Medicinal woody plants, especially medicinal tall trees, play a same important
      role in forest structure, ecological balance and timber production as other tree
      species in forest, and due to their additional medicinal values overuse of these
      trees is more intensive than others. Many medicinal materials are destructively
      obtained from plants such as roots or bark used as medicinal materials. The
      contradiction between the utilization and protection of medicinal woody plants
      becomes more and more incisive. In the present paper, based on the analysis of
      the utilized situation and specialty of medicinal woody plants, the trouble
      between the plants protection and utilization was observed, the method to solve
      it and the fundamental research work needs to be developed were discussed. The
      following aspects of researches were suggested to be conducted: (a) study on the
      distribution in organs, seasonal and age variations, and correlation with
      environmental factors of principal medicinal compositions in mature trees to
      clear the optimum of harvest and cultivation conditions; (b) study on the
      distribution in organs, seasonal and age variations, and correlation with
      environmental factors of principal medicinal compositions in saplings, especially
      the time course of the variation in medicinal compositions and biomass to achieve
      the optimal tree ages for the balance between biomass and production of medicinal
      products during saplings development; (c) study on the influence and regulation
      of environmental factors on medicinal compounds production in woody plants to
      look for the optimal cultivated conditions for optimizing the accumulation of
      biomass and medicinal chemicals; (d) further study on the regulatory mechanism of
      the induced production of main medicinal compositions by ecological factors at
      protein (key enzyme) and gene level to accumulate fundamental data for the
      enhancement of quality and quantity, and approach of new accesses to medicinal
      products using biological technology (cell culture and gene technology). Aimed at
      medicinal woody plants in Chinese forest resources, to develop the fundamental
      researches on resources protection and rational utilization will create many
      profound scientific significances. Firstly, medicinal woody plants are the
      important components of Chinese natural forest resources, so the problem for
      their protection and utilization, especially for that of tall trees, is quite
      remarkable and special. To reveal the internal contradictory between plant
      resources protection and its reasonable exploitation and exploit a practicable
      access to solve it will promote and accelerate the fulfillment of "natural forest
      protection project" in China. Secondly, traditional Chinese medicine is a main
      part of Chinese excellent ancestral culture, and the traditional utilizing models
      have been carried on for thousands of years. Accompanying with the development of
      human society, many unavoidable troubles such as the shortage of natural
      resources and the pollution of natural environment are more and more severely,
      which make the old models of the traditional Chinese medicine become more and
      more harmful and inaccessible to mankind. New substitutive approach to the
      utilization of traditional Chinese medicine, especially to that of Chinese
      medicinal woody plants will be one of the key methods to improve the present
      situation. Thirdly, traditional Chinese medicine, the cherish treasure of Chinese
      ancestral culture, need not only be preserved but also be developed. One of the
      main problems to restrict the extensive spread of the traditional Chinese
      medicine is its unstable quality, so to reach the stable quality and good quality
      is tightly linked to the improvement of traditional Chinese medicine. Hence the
      environmental regulation to the cultivation of medicinal plants, which can prove
      and guarantee the stable and high quality, will fit the demand on the production
      of medicinal plant material, and correspond to the goal of great efficacy and
      superior quality during the course of modernization of traditional Chinese
      medicine.

PMID- 14733022
TI  - [Mycorrhizal diversity and its significance in plant growth and development].
AB  - Mycorrhizal diversity, including morphological, species and functional diversity,
      is an integrative component of biodiversities. Many experiments showed that
      mycorrhizal diversity played an important role in the origin, evolution,
      distribution, survival, growth and development of plants. But, mycorrhizal
      diversity is dependent on plant diversity. It was suggested that mycorrhizal and
      plant diversities stimulated or retarded each other. The significance of
      mycorrhizal diversity in plant diversity was also discussed.

PMID- 14733023
TI  - [Spatio-temporal problems of geographic information system in marine fishery].
AB  - In marine fisheries, it is very important to understand and grasp the spatio
      temporal nature. Geographical Information System (GIS) has been applied to
      describe or forecast the dynamic trend of resources or to set up evaluation
      model, which is one of high technologies in modern marine fisheries. Based on the
      review of the development of marine fishery GIS (MFGIS), four spatio-temporal
      problems it occurred were discussed, and the possible resolutions were
      prospected.

PMID- 14733024
TI  - [Several research hotspots in river ecology].
AB  - River ecology is a vital field in limnological research, and several new theories
      and methods have been developed and used in the study of lotic systems. In this
      article, a summary of these new theories was introduced, which includes river
      continuum concept, ecological water consumption of river ecosystem, services and
      health of river ecosystem, ecosystem management, and watershed ecology. The
      authors suggested that the research of river ecology should be carried out on the
      scale of watershed, and that the combination of ecosystem health and ecosystem
      services could be the key point in the sustainable development management of
      river ecosystem. Seeing that there are few studies in this area in China,
      relevant research should be conducted as soon as possible.

PMID- 14733025
TI  - [Ecological studies on genetically engineered microorganism in environment].
AB  - This paper discussed the main problems which should be considered on the
      environmental release of genetically engineered microorganism (GEM), including
      GEM construction, gene transfer, fitness, diffusion, translocation, potential eco
      influence and so on. Moreover, aiming at the special ecological characteristic
      and eco-influence of GEM, this paper brought forward the policy of "respective
      analysis on different problems", and postulated the corresponding projects of GEM
      ecological research to apply GEM safely and effectively in nature.

PMID- 14733027
TI  - [Effect of bacterivorous nematodes on bacteria population under gnotobiotic
      culture].
AB  - A gnotobiotic microcosm experiment was conducted to study the influence of
      bacterivorous nematodes (Protorhabditis sp.) on bacteria (Pseudomonas
      fluorescens) population under different conditions including substrate
      concentration, oscillation pattern, and numbers of nematodes inoculated. When the
      bacteria were incubated under intermittent oscillation by hand (6 times at 0.5 h
      intervals, 22 degrees C), their growth was stimulated in the presence of
      nematoedes, and the bacteria grew faster with the increase of nematode numbers
      and substrate (liquid potato-sucrose medium) concentration. However, when the
      incubation was under continuous oscillation (100 rpm, 22 degrees C), bacteria
      population was deflated with the addition of nematodes, and the inhibition was
      greater when a higher concentration of substrate was used. It was found that the
      stimulation or inhibition of bacteria population by nematodes occurred in the
      logarithmic stage of bacteria growth. The optimal and over-grazing of nematodes
      on regulating bacteria population was discussed.

PMID- 14733026
TI  - [Toxic effects of Cd2+ pollution on the biochemical and physiological characters
      and ultrastructure of Alternanthera philoxeroides].
AB  - By imitating different concentration Cd2+ polluted water environment, this paper
      dealt with the changes of some biochemical and physiological characters and the
      damage of ultrastructure in leaves of Alternanthera philoxeroides. The result
      showed that SOD and POD activity first increased in the low concentration
      pollution and then decreased with the concentration of pollution raised. The
      content of chlorophyll, chlorophyll a/b value, CAT activity and the content of
      soluble protein all declined continually. With the concentration of pollution
      increased, the ultrastructure of cell nuclei, chloroplast and mitochondria became
      deformed, the permutation of structure inside disordered, swelled, membrane
      disrupted and vesiculated. The changes of some biochemical and physiological
      characters accorded with the damage of cell ultrastructure.

PMID- 14733028
TI  - [Acute lethal and behavioral response of Liposcelis bostrychophila (Psocoptera:
      Liposcelididae) to DDVP].
AB  - Book louse Liposcelis bostrychophila is a minor pest in stored products, and may
      seriously infest the stored products when its population outbreaks. This study
      was conducted to evaluate the toxic effect of DDVP on various development stages
      of L. bostrychophila. The results showed that at 28 +/- 0.5 degrees C and 24 h
      exposure under 75%-80% RH, the LC50 of the eggs, larvae of 1st to 4th stadium,
      and adults was 16.83, 0.22, 0.22, 0.23, 0.26 and 0.25 micrograms.L-1,
      respectively. The lethal effect of DDVP on the adults at different exposure
      periods showed that their mortality was linearly related to the treated time,
      implying that the test colony of L. bostrychophila was susceptible to DDVP. In
      the practical fumigation, DDVP as a fumigant had a good effect on the pest
      control if the development stage, time and periods of treatment were appropriate.

PMID- 14733029
TI  - Comparison of mortality outcomes derived from survival curves calculated by the
      mean covariates and corrected group prognosis methods.
AB  - As creators of mortality abstracts, we assume the mortality and survival curves
      from source articles have been created by the appropriate methodology. Two
      methods can be used to generate adjusted curves--the mean of covariates and the
      group prognosis methods. The use of the former, although simple to implement, may
      be mathematically problematic. A comparative mortality analysis is created from a
      study population using curves adjusted by both methods. For this cohort,
      utilizing data from direct measurement of enlarged survival curves produced no
      difference in mortality outcomes. Small differences in percent cumulative
      survival derived from each method do not translate into important differences in
      mortality ratios and excess deaths.

PMID- 14733030
TI  - Study of policies on insured lives with elevated blood pressure known at time of
      issue.
AB  - BACKGROUND: The mortality results of policies on insured lives with elevated
      blood pressure have been the subject of several studies since the early 20th
      century. This study, which began with issues of 1989, utilizes data from the
      Impairment Study Capture System (ISCS). Data are also compiled for impairments
      other than elevated blood pressure in the ISCS for the same study period. A
      comparison of these 2 sets of data shows the relative severity of elevated blood
      pressure compared to all other impairments combined. The determination of
      elevated blood pressure was made on the basis of risk classification due to lack
      of specific blood pressure readings. METHODS: Mortality results are actual to
      expected ratios based on the SOA 1990-95 Select Basic Table. The companies
      participating in this study have completed 3 steps: (1) agreement to have
      individual reports to the MIB included in the ISCS file; (2) submission of
      additional policy information, not on the MIB report; and (3) update of in-force
      status annually. Reports do not include personal identifying information.
      RESULTS: Based on the limited amount of data contributed by relatively few
      companies, there has been considerable improvement since earlier studies in
      mortality among insureds with elevated blood pressure. Some possible reasons for
      this include: (1) fewer smokers--there were fewer smokers in the population and
      hence applying for insurance during the period covered by this study as compared
      to earlier studies; (2) improved treatment, patient awareness and adherence to
      regimen--a wider variety of medications and current treatment practices compared
      to treatment in the 1970s and early 1980s may have influenced results. Compared
      to prior studies, it is likely that more insureds with elevated blood pressure
      first noted on the insurance examination subsequently have received treatment. In
      addition, those with elevated blood pressure have become more aware of the
      importance of adhering to their medication regimen and improving other adverse
      risk factors; (3) improvement in the treatment of related medical conditions.
      CONCLUSION: The results of this study must be interpreted with caution. The
      volume of data is not substantial, and the results may not be representative of
      non-contributing companies. Going forward, it is hoped that more companies will
      agree to participate such that future studies will produce data and results of
      greater utility.

PMID- 14733031
TI  - Breast cancer: a review of the literature.
AB  - This article presents a comprehensive review of the Breast Cancer literature
      examining epidemiology, diagnosis, pathology, "benign" breast disease, breast
      carcinoma in situ syndromes, staging, and post-treatment surveillance among many
      topics. Breast cancer remains the most commonly occurring cancer in women. Breast
      cancer detection, treatment, and prevention are prominent issues in public health
      and medical practice. Background information on developments in these arenas is
      provided so that medical directors can continue to update their approach to the
      assessment of breast cancer risk.

PMID- 14733032
TI  - Diabetes mellitus related morbidity, risk of hospitalization and disability.
AB  - OBJECTIVE: To investigate the rates of complications, hospitalizations and
      disabilities attributable to type 1 and type 2 diabetes mellitus (DM) combined,
      unless otherwise noted. METHODOLOGY: Risk assessment of DM-related morbidity,
      hospitalizations and disabilities using data from the medical literature and
      health statistics on the population. Calculation of morbidity, hospitalization,
      and disability ratios (MbR, HR, DR) will allow comparison of observed rates in
      people with DM to those reported in the nondiabetic population. RESULTS: MbRs
      vary according to the morbid condition studied: approximately 300% at age 45-64
      years for ischemic heart disease, 533% for coronary heart disease or stroke, 226%
      to 388% for chronic heart failure, 560% for peripheral vascular disease, 380% for
      neuropathy at age 35-74 years, 890% to 2225% for lower limb amputations, 1458% to
      3287% for end-stage renal disease. For ocular complications: cataracts, 165% to
      232%; glaucoma 140% to 330%; trouble seeing, 180% to 231%; blindness at age > or
      = 65 years, 517%. Higher values are noted at younger ages. HR: 200% to 409%. DR:
      217% to 328%. CONCLUSION: Among diseases, DM is one of the leading and growing
      causes of hospital admission and disability. Precise risk assessment of morbidity
      is essential for realistic underwriting of health and disability insurance.

PMID- 14733033
TI  - Tracking levels of psychiatric distress associated with the terrorist events of
      September 11, 2001: a review of the literature.
AB  - BACKGROUND: Early publicized predictions of an onslaught of psychiatric distress
      following the terrorist events of September 11, 2001, have not materialized, and
      it remains unlikely at present that the medical and insurance communities will
      experience a significant increase in psychiatric utilization rates secondary to
      September 11. A handful of research studies have begun to characterize the
      psychiatric impact of the events associated with the September 11 terrorist
      attacks. Information related to the manifestation of psychiatric distress
      following disasters is of particular interest to the scientific, clinical and
      disability insurance communities given the ongoing threat of further terrorist
      attacks. METHODS: A comprehensive literature search was completed to identify
      articles that address our current understanding of posttraumatic stress disorder
      (PTSD) and patterns of psychiatric distress that typically follow manmade
      disasters. To help in conveying such a conceptual framework, we integrated basic
      research relating to PTSD with epidemiological data relating to past disasters
      (e.g., the Oklahoma City bombing) and the events of September 11. RESULTS AND
      CONCLUSIONS: A critical analysis of the September 11 research literature is
      offered with suggestions for research that would strengthen our understanding of
      the manifestation of psychiatric distress associated with manmade disasters.

PMID- 14733034
TI  - Kawasaki disease.
AB  - Kawasaki disease is currently the leading cause of acquired heart disease in
      children in the United States and Japan. The case of an 18-year-old insurance
      applicant is used to review the pathogenesis, complications, treatment and
      prognostic implications of this disorder.

PMID- 14733035
TI  - Causes of death in the elderly.

PMID- 14733037
TI  - Ambulatory blood pressure monitoring: the panacea test for hypertension
      management or an unnecessary diagnostic luxury?

PMID- 14733036
TI  - Hitting moving targets.

PMID- 14733038
TI  - The 2002 annual report of the Regional Infant and Child Mortality Review
      Committee.
AB  - The annual report of the Regional Infant and Child Mortality Review Committee
      (RICMRC) is attached. This Committee has as its mission the review of infant and
      child death so that information can be transformed into action to protect young
      lives. The 2002 review area includes South Dakota's Minnehaha, Turner, Lincoln,
      Moody, Lake, McCook, and Union counties. In 2002 there was one death in this
      region due to SIDS, plus one infant death due to positional asphyxia that
      illustrates the hazards of soft bedding and prone sleeping. These data reflect
      the need to remain vigilant in the public campaign to promote "back to sleep" and
      safe sleeping environments for infants. There were four other deaths due to
      accidental injury, mostly representing immaturity in driving various vehicles. In
      2002 there were two child abuse homicides, and three teenage suicides. The RICMRC
      invites other communities to join in its efforts to review deaths to prevent
      potential life-threatening hazards to children in their local environs.

PMID- 14733039
TI  - Advanced ovarian carcinoma as a chronic disease: a case report and review.
AB  - Epithelial ovarian cancer is the fifth most common visceral malignancy in U.S.
      women, with the highest incidence in the sixth decade. There are often no early
      manifestations. Approximately 70% of patients present with advanced disease.
      Transvaginal ultrasonography is the single most useful test in the evaluation of
      a suspected pelvic mass. Treatment is based on the stage of the disease at
      presentation. Surgery is the mainstay of treatment. Chemotherapy is important in
      controlling residual disease following cytoreductive surgery and as neoadjuvant
      therapy in patients with advanced disease. The standard chemotherapy for advanced
      ovarian cancer is currently paclitaxel-carboplatin or paclitaxel-cisplatin. We
      present a patient who had an unusually prolonged survival after receiving
      ifosfamide-based combination chemotherapy. The data from the Sioux Valley
      Hospital USD Medical Center Cancer Registry also suggests that ifosfamide-based
      combination chemotherapy prolongs survival in patients with advanced ovarian
      cancer.

PMID- 14733041
TI  - Privacy and the health information domain: properties, models and unintended
      results.

PMID- 14733040
TI  - Risk management, clinical guidelines, clinical pathways and health law.

PMID- 14733042
TI  - A presentation of the Belgian act on euthanasia against the background of Dutch
      euthanasia law.

PMID- 14733043
TI  - Legal analysis of the Spanish Basic Law 41/2002 on the autonomy of the patient
      and the rights and obligations with regard to clinical information and
      documentation.

PMID- 14733044
TI  - Human assisted procreation and human rights--the Greek response to the felt
      necessities of the time.
AB  - The new reproductive technologies enable otherwise infertile couples to reproduce
      noncoitally. Problems arising from the new reproductive techniques refer to the
      persons entitled to have access thereto, to the methods accepted (such as
      procreation by means of a surrogate mother), to the storage and donation of
      gametes and embryos, to donor anonymity etc. Although homologous and heterologous
      insemination and in vitro fertilisation have been performed in Greece for a long
      time, legal provisions thereon have been established only recently: Law 3089/2002
      on assisted procreation builds the respective legal frame, regulating main
      aspects in this crucial field of interwoven human rights and social duties.

PMID- 14733045
TI  - Patient's rights in Bulgaria.

PMID- 14733046
TI  - Xenotransplantation, public responsibility and law.

PMID- 14733047
TI  - Council of Europe (Recommendation of the Committee of Ministers to member states
      on xenotransplantation).

PMID- 14733048
TI  - European courts. CJEC 2003/3 case C-156/01, Van der Duin.

PMID- 14733049
TI  - European Court of Human Rights. ECHR 2003/3 case of Stambuk v. Germany, 17
      October 2002, no. 37928/97 (third section).

PMID- 14733050
TI  - The Belgian act on euthanasia of May, 28th 2002.

PMID- 14733051
TI  - Are you a workaholic?

PMID- 14733052
TI  - HIPAA and homeland security. Can they coexist?

PMID- 14733053
TI  - A peaceful death--side by side.

PMID- 14733054
TI  - San Diego's burning.

PMID- 14733055
TI  - Want a better deal? Ask.

PMID- 14733056
TI  - Do these doctors give medicine a black eye?

PMID- 14733057
TI  - Translating insurance-speak for patients.

PMID- 14733058
TI  - The risk of treating friends and family.

PMID- 14733059
TI  - Never underestimate a patient.

PMID- 14733060
TI  - ["Psychotherapeutic medicine"].

PMID- 14733061
TI  - [2-stage group psychotherapy with integrated autogenic training within the scope
      of a general integrated psychotherapy concept].
AB  - Group-therapy and autogenic training in combination show mutual potentiation. Our
      results have proved the hypothesis to be true and we have also been able to
      explain it by an analysis of the neurophysiological and psychological findings
      concerning both methods. Our "model" has proved to be very economical in time and
      can be easily applied. It needs basic psychotherapeutical education but no
      special additive schooling. It is particularly well employed in rehabilitation
      patients, elderly patients and geronto-rehabilitation patients. As numbers of
      such patients are steadily increasing, it could soon become highly important, and
      in the technically dominated medicine of today, the particularly communicative
      component that we postulate in integrated psychotherapy could also grow in
      importance. By combining the two methods, it is not method that is at the centre
      of our endeavours but the patient.

PMID- 14733062
TI  - [The geriatric psychiatry patient--a new indications field for psychotherapy?].
AB  - Despite the fact that 9% of the elderly would need psychotherapeutic treatment,
      only 1% of the applications for such treatment were initiated by the elderly.
      Older people often lack the ability to verbalize their emotional problems, which
      is an obvious prerogative for expressing the wish for psychotherapy. However
      elderly people tend to indulge in childhood memories, and therefore would be
      excellent candidates for psychoanalytic-orientated treatment. Because objective
      time is not a factor in subconscious life, older people can suffer from unsolved
      intrapsychic-, intra- and intergenerational conflicts and trauma reactivations.
      Without considering these psychological conflicts, the most important fields for
      psychotherapeutic intervention in the elderly are depression, mild cognitive
      impairment, incipient demential syndromes, and the impairment of psychosocial
      competence resulting from these conditions; caregiver-related therapy also plays
      an important role. For those between 65 and 75 years of age, the indications for
      psychotherapy are similar to those of younger adults: first of all depression,
      anxiety-syndromes, insomnia and suicidal attempts. For those over 75 years old,
      isolation, polymorbidity, preservation of autonomy and self-determination, and
      the fear of loosing autonomy and becoming care-dependent are the most important
      indications for psychotherapy. A feature common to all psychotherapeutic schools
      is that they try to overcome disturbances, to reduce emotional pain, to preserve,
      establish and improve psychosocial competency and the activities of daily living.
      Psychotherapy in a narrow sense is indicated when the psychic structure, the
      mental flexibility and the motivational state are quite good and if
      differentiated verbal interactions are possible. In a broader sense,
      psychotherapy stands for actional and training aspects, and integral
      environmental and socio-therapeutic treatment so that autonomy and quality of
      life can be properly improved. This definition of psychotherapy makes it obvious
      that demented and care-dependent patients are potential candidates for
      psychotherapy.

PMID- 14733063
TI  - [Inpatient-ambulatory network of psychotherapy care].
AB  - The development and state of the art is presented for inpatient psychotherapy in
      neurotic and psychosomatic patients. The question is then posed whether time
      tested inpatient psychotherapy can survive the introduction of "diagnosis-related
      groups" (DRG) with its threat of flat-rate case billing. Thus, the development of
      an "in- and outpatient network" has been considered as a possible alternative, in
      which hospitals and private practices combine intervals of inpatient and
      outpatient psychotherapy.

PMID- 14733064
TI  - [Psychotherapy in a tax-financed sectorized health care system--a happy ending or
      disaster for English patients?].
AB  - Compared to other European countries' health systems, the NHS is very different.
      Finance by taxes, standards set by frameworks and statutory bodies to monitor
      nationwide the outcome, are virtually unknown on the Continent. For the patients
      there are considerable differences in how they are referred to psychotherapy and
      receive their treatment based on guaranteed standards. Health professionals
      identified with the NHS have to cope with a plethora of government directives.

PMID- 14733065
TI  - [Topical immunomodulators for treatment of eczema].
AB  - Anti-inflammatory treatment of eczematous skin diseases like atopic dermatitis
      and allergic contact dermatitis has mainly been performed with topical
      glucocorticosteroids. Increasing knowledge of the pathophysiological interactions
      and the immunological mechanisms during the chronic inflammatory processes in the
      skin offers new therapeutical options. In this review, new therapeutical
      approaches for the treatment of eczematous skin disease will be presented. These
      novel compounds include the topical immunomodulators, tacrolimus and
      pimecrolimus. Such molecules inhibit intracellular signal transducing
      phosphatases and act consecutively at the molecular level by inhibiting the
      activation of transcription factors. Secondly, the development of nuclear hormone
      receptor family members, such as retinoids, vitamin D and peroxisome proliferator
      activated receptor agonists, is discussed. Substances from this family have
      differentiating, antiproliferative, but also immuno-modulatory effects, which
      make them attractive as anti-eczematous therapeutic compounds. The diversity of
      these interactions is extensive, and clinical studies will prove their clinical
      efficacy.

PMID- 14733066
TI  - [Psychopathologic deficits after polytrauma in childhood and adolescence].
AB  - PURPOSE: The aim of this report was to evaluate psychological deficits following
      polytrauma in childhood and adolescence as well as to detect psychological
      vulnerable phases during the treatment period. METHODS: From 9/92 to 12/98, 41
      polytrauma patients (18a or younger) were treated at the University of Vienna
      Medical School, Trauma Center. Out of the 28 survivors, patients with head
      injuries and congenital neurological deficits were excluded, leaving 10 young
      patients that were eligible for psychological testing after a mean follow-up of
      3.4 years (range, 1 to 7 years). Besides catamnesis and diagnostic interviews, an
      evaluation of cognitive functions as well as personality tests were performed.
      RESULTS: The diagnostic interviews revealed mild psychiatric symptoms in 2/10
      patients, but the cognitive functions did not show any deficits compared to
      normal values. The personality tests presented stress-avoiding strategies and an
      increased anxiety sensitivity in 2/10 patients. The catamnesis constantly
      revealed 2 vulnerable phases in all patients: 1. the transfer from the intensive
      care unit to the normal ward, 2. the retransfer to the domestic field after a
      long hospital stay. CONCLUSIONS: The present report suggests that the long-term
      psychological outcome following polytrauma in childhood and adolescence may be
      good, without any major disorders. The described critical phases during treatment
      demonstrate that psychological support in the young, severely injured patient
      should start very early on at the intensive care unit.

PMID- 14733067
TI  - [Etiology and prognosis of "internal medicine" acute renal failure in 1981-1990
      and 1991-2000--an analysis of 510 cases in a single center].
AB  - Despite advanced techniques of renal replacement therapy as well as improved
      medical care and control over the last decade, the overall mortality of patients
      with "internal" nontraumatic acute renal failure (ARF) requiring replacement
      therapy is still high. In a retrospective study we compared causes of
      nontraumatic ARF, risk factors for the development of renal failure and mortality
      rates in patients with nontraumatic ARF, who received hemodialysis therapy from
      1981 to 1990 and from 1991 to 2000. 510 patients with nontraumatic ANV requiring
      hemodialysis were evaluated, 278 patients in 1981-1990 and 232 patients in 1991
      2000. In both groups the chronic risk factors for ANV such as hypertension,
      diabetes mellitus, chronic cardiac failure, chronic hepatic failure and pre
      existing renal impairment and the causes of a traumatic ARF were compared. In
      addition, concomitant sepsis and multi-organ failure as prognostic parameters as
      well as mortality rates dependent on the causes of ARF were evaluated. In the
      latter period, there was a significant reduction in the prevalence of acute
      glomerulonephritis (3.0 versus 8.3%, p < 0.05) and acute interstitial nephritis
      (2.6 versus 7.6%, p < 0.05) as well as acute pancreatitis (1.7 versus 7.6%, p <
      0.01) as causes of ARF. On the other hand, the prevalence of drug-induced ARF
      increased during the latter period (10.8 versus 4.7%, p < 0.05). Other etiologies
      of nontraumatic ARF did not significantly differ between the two decades.
      Patients treated from 1991 to 2000 had chronic risk factors for the development
      of ARF, namely diabetes (14.6 versus 6.8%), coronary artery disease (28.0 versus
      9.3%) and pre-existing renal impairment (51.7 versus 17.6%, p < 0.001), more
      frequently than did patients dialysed from 1981-1990. The prevalence of sepsis
      and multi-organ failure was approximately the same in both periods. The overall
      mortality (41.8 versus 44.6%, NS) and mortality secondary to causes of
      nontraumatic ARF were similar in both periods. In summary: the prevalence of
      several causes of nontraumatic ARF has changed during the last decades.
      Furthermore, patients treated in the 90's had chronic risk factors for renal
      failure, namely diabetes and pre-existing renal impairment as well as coronary
      artery disease, more frequently than did subjects treated in the preceding time
      period. The prognosis of the patients has not been significantly improved.

PMID- 14733068
TI  - Langhans vs Langerhans: a perennial confusion.

PMID- 14733069
TI  - Payback time.

PMID- 14733070
TI  - Delayed discharge. Fine tuning.

PMID- 14733071
TI  - Analysis. Illuminate the debate.

PMID- 14733073
TI  - Clinical management where medicine meets management. Ever ready.
AB  - 'Evercare nurses', based on a US model of an expanded clinical role, are being
      piloted in 10 trusts. Pilots report good results in increasing quality of social
      care. There has been criticism of diverted resources and unthinking importing of
      US ideas.

PMID- 14733074
TI  - Easy-to-swallow solution.

PMID- 14733075
TI  - Intellectual property. Device trade.
AB  - Potential is growing for trusts to benefit from patented innovation through nine
      regional knowledge hubs. Legal protection of intellectual property is essential
      to ensure copyright. 'Inventions' can boost trust finances, support the local
      economy and spread innovation throughout the NHS.

PMID- 14733077
TI  - HSJ people. TIN it to win it.

PMID- 14733076
TI  - Finance. Do tariffs stack up?

PMID- 14733078
TI  - [How do diazepam and flumazenil influence respiratory control by the activities
      of both hypoglossal and phrenic nerves in rabbits?].
AB  - BACKGROUND: Upper airway obstruction and inadequate ventilation often arise
      during sedation and anesthesia by benzodiazepines. To estimate the influence of
      benzodiazepines on the respiratory control, we studied the effect of diazepam and
      flumazenil on the neural activity and the respiratory response caused by a brief
      (60 sec) respiratory arrest (RA) observed in the hypoglossal nerve (HG) and
      phrenic nerve (PH) in rabbits. METHODS: Experiments were preformed on adult
      rabbits vagotomized, paralyzed and ventilated artificially with 50% N2O, 50%
      oxygen and 0.3-0.5% sevoflurane. We evaluated and compared the effects of
      diazepam and flumazenil on the peak amplitude (AMP-HG&PH) and the root mean
      square (RMS-HG&PH) of HG and PH, and respiratory cycle (Tc). RESULTS: Diazepam
      depressed HG activity more than PH activity with no influence on Tc. But it did
      not cause dose-related depression. Flumazenil 0.2 mg.kg-1 completely reversed the
      respiratory depressions caused by diazepam with the increased Tc. In addition to
      augmentation of the hypoglossal activity in inspiration, flumazenil caused a rise
      in its activity in pan-expiratory period in some cases. Additional administration
      of diazepam 6 mg.kg-1 following flumazenil depressed PH activity again, but did
      not affect HG activity any more. There was no significant depression in
      cardiovascular parameters with tested dosages of diazepam and flumazenil. RA
      response was characterized by raised AMPs and augmented RMSs (delta AMPs, delta
      RMSs) with marked prolongation in Tc (delta Tc). Diazepam depressed RA response
      dose dependently, but flumazenil did not seem to antagonize this depression.
      CONCLUSIONS: These results suggest that 1) flumazenil is not only a specific
      antagonist of benzodiazepines but also a potential excitatory agent of
      hypoglossal nerve activity, and that 2) there is some functional diversity in
      disposition of benzodiazepine-receptor binding GABAA-receptor responsible for
      neural respiratory control system.

PMID- 14733079
TI  - [The effects of heat stimulation and cold stress on the rats with cervical
      sympathectomy].
AB  - BACKGROUND: To investigate the general action of stellate ganglion block (SGB),
      we examined the effects of heat stimulation and cold stress on the behavior and
      stress hormone of the bilateral cervical sympathectomy rats as a long-term and
      repeated SGB model. METHODS: Wistar's male rats were divided into three groups:
      control (C), sham operation (S) and sympathectomy (Sx) groups. After 2 weeks, two
      experiments were done. One was measurement of escape response time from the heat
      stimulus and the other was hormone measurement. Serum adrenocorticotropic hormone
      (ACTH), alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphine
      (beta-END) levels were measured assigning 3 groups to 2 subgroups with and
      without cold stress. RESULTS: Escape response time was significantly extended in
      the Sx group. ACTH in the Sx group was significantly higher than in other groups,
      but changes of ACTH by cold stress were similar in 3 groups. In the Sx group
      alpha-MSH was hardly changed by cold stress while alpha-MSH was significantly
      decreased in the S group. Changes of beta-END by cold stress were similar in the
      S and Sx groups. CONCLUSIONS: These results suggest that SGB works systemically
      through hypothalamus endocrine system and affects stress hormone differently.

PMID- 14733080
TI  - [Incidence and clinical characteristics of perioperative pulmonary
      thromboembolism under the use of intermittent pneumatic compression as a
      preventive measure].
AB  - Pulmonary thromboembolism (PTE) is a crucial complication characterized by rapid
      onset and a high mortality rate. There are few reports concerning perioperative
      incidence of PTE and deep vein thrombosis (DVT) among Japanese population. All
      surgical patients excluding young patients for minor surgery were equipped with
      calf- or thigh-length intermittent pneumatic compression (IPC) device as a DVT
      preventive method during the period of immobility. Incidence and clinical
      characteristics of perioperative PTE and DVT under the use of IPC device were
      analyzed at Kobe University Hospital. One patient developed DVT and four patients
      developed PTE among the 6500 surgical cases. All patients with DVT or PTE were 66
      years or older, and all patients were diagnosed by computer tomography,
      venography and pulmonary angiography between 7 to 14 days after each operation.
      One patient was surgically treated by embolectomy and removal of intraarterial
      thrombus, and others were treated with thrombolysis, anticoagulants and placement
      of vena cava filters. For prevention of DVT and PTE, other preventive methods
      such as anticoagulants and prolonged application of IPC should be necessary.

PMID- 14733081
TI  - [Epidural blood patch as a successful treatment of Barre-Lieou syndrome: report
      of two cases].
AB  - Barre-Lieou syndrome accompanies neurological symptoms after neck sprain, and is
      often difficult to treat. We describe two young men with various neurological
      symptoms after traffic accident, who were diagnosed with Barre-Lieou syndrome.
      Both case 1 (41-year-old man) and case 2 (34-year-old man) showed no abnormal
      findings in head and cervical X-ray, CT-scan and MRI. Only radionuclide
      cisternography (RNC) showed cerebrospinal fluid (CSF) leak into epidural space at
      thoracolumbar level. Three months (case 1) and four years (case 2) had passed
      after each accident. Two patients underwent epidural blood patch (EBP) for total
      of three times. The average volumes of the blood used for EBP were 30 ml (case 1)
      and 24 ml (case 2). The procedure improved various symptoms except for neck
      stiffness and dizziness. EBP had led to low back pain, which disappeared within
      three days. CSF leak vanished in RNC after EBP. Severe complication, for example
      epidural infection or neurological disorders due to hematoma, was not noticed.
      While neural blockade did not relieve pain before EBP, we could get good effect
      from neural blockade for remaining symptoms after EBP. We consider that Barre
      Lieou syndrome is due to CSF leak and EBP may be one of the useful treatments.

PMID- 14733082
TI  - [A case of ligation of the left pulmonary artery during total arch replacement
      for aortic arch aneurysm].
AB  - Pulmonary artery embolism is one of the most severe complications that can occur
      in the perioperative period. We report a case of left pulmonary artery
      obstruction during total arch replacement, which occurred during cardiopulmonary
      bypass (CPB) for severely invasive procedures. A 59-year-old male was
      anesthetized for total arch replacement using a double-lumen endobronchial tube
      (Bronco-Cath 39 F left) in the supine position. The surgery was performed under
      deep hypothermic circulatory arrest and CPB. When the CPB was finished and
      mechanical ventilation was started, PaCO2 was unusually elevated. Furthermore,
      end-tidal CO2 was decreased and no CO2 was expired from the left side of the
      double-lumen tube. Left pulmonary embolism was highly suspected and pulmonary
      artery angiography was performed. As the complete obstruction of the left
      pulmonary artery was demonstrated, pulmonary artery reconstruction was performed.
      The reason for the obstruction was the surgical ligation during CPB. The wall of
      the aneurysm was attached to the left pulmonary artery and when it was removed,
      the left pulmonary artery was injured. The systemic circulation remained stable,
      however, despite reports that pulmonary embolism was very dangerous and often
      caused the patient's death.

PMID- 14733083
TI  - [Anesthetic management with ATP for endovascular thoracic aortic repair].
AB  - A 78-year-old man with thoracic aortic aneurysm was scheduled for endovascular
      stent-graft surgery without cardiopulmonary bypass. He had a history of
      myocardial infarction five months before and echocardiography revealed ejection
      fraction of 37%. Deployment of the stent-graft was performed during third degree
      atrioventricular (A-V) block of 32 seconds produced by adenosine 5'-triphosphate
      (ATP) 30 mg. There were no complications during this procedure. ATP is a
      convenient and suitable agent to produce transient A-V block for the precise
      deployment of the stent-graft in these patients with severe cardiopulmonary
      complications.

PMID- 14733084
TI  - [A case of suspected pulmonary thrombosis in a patient with reactive
      thrombocytemia who underwent liver subsegmentectomy].
AB  - A 68-year-old man with reactive thrombocytemia (platelet count: 97.2 x 10(4).mm
      3) underwent liver subsegmentectomy for hepatocellular carcinoma. Thoracic
      epidural combined with general anesthesia was carried out for the surgery.
      Platelet aggregability was monitored during the operation. At the beginning of
      the operation, platelet aggregability to aggregating factor ADP showed an
      abnormal pattern without dose dependency. In spite of continuous administration
      of gabexate mesilate for inhibition of thrombosis, the patient developed
      hypercapnia with low end tidal CO2 pressure (PETCO2) and hypoxia, suggesting
      pulmonary embolism. PETCO2 and SPO2 recovered soon after heparin administration.
      The patient recovered without any neurologic complications. This case
      demonstrated that hyperaggregability is possible in patients with thrombocytemia
      and suggests that monitoring of platelet function in patients with thrombocytemia
      is difficult.

PMID- 14733085
TI  - [Retroperitoneal emphysema during total hip replacement].
AB  - A 55-year-old woman with rheumatic arthritis was scheduled for total hip
      replacement. The procedure was performed under combined spinal and epidural
      anesthesia. Intraoperatively, the part of acetabular roof was cracked by reaming
      the region but she did not complain of any symptom. However, during pulse
      irrigation she complained of abdominal pain. After the operation, abdominal
      distension was noticed and retroperitoneal emphysema was disclosed. She was
      managed in a ward without problems postoperatively.

PMID- 14733086
TI  - [Effects of diltiazem on contractility and electromyographic activity of non
      fatigued diaphragm in dogs].
AB  - BACKGROUND: No data are available for diltiazem on muscle function (contractility
      and electomyographic activity) of non-fatigued diaphragm. METHODS: Eighteen
      pentobarbital-anesthetized dogs were divided into 3 groups of 6 each: Group I
      received no drug; Group II received small-dose of diltiazem (0.1 mg.kg-1.h-1);
      Group III received large-dose of diltiazem (0.5 mg.kg-1.h-1). Diaphragmatic
      contractility was assessed by transdiaphragmatic pressure (Pdi), the difference
      between esophageal and gastric pressures. Diaphragmatic electromyographic
      activity (Edi) was measured by means of electrodes placed at the anterior portion
      of the crural and costal parts of the diaphragm. After measuring baseline values
      of Pdi and Edi at 20 Hz and 100 Hz stimulation, the study drug was administered
      for 30 min. RESULTS: With infusion of diltiazem, Pdi and Edi to each stimulus did
      not change in Groups II and III. In Group I, these variables also showed no
      change. CONCLUSIONS: Diltiazem, at doses below 0.5 mg.kg-1.h-1, does not affect
      contractility and electromyographic activity of non-fatigued canine diaphragm.

PMID- 14733087
TI  - [Anesthetic management of a patient with non-bullous congenital ichthyosiform
      erythroderma].
AB  - Non-bullous congenital ichthyosiform erythroderma is a disorder in the
      cornification of the skin, histopathologically characterized by hyperkeratosis.
      Previous reports mentioned that the fixation of endotracheal tubes and ECG
      electrodes to the skin was likely to be infirm in the patients with this
      disorder, and that the patients' body temperatures were easily affected by the
      environment. A 3-year-old girl with non-bullous congenital ichthyosiform
      erythroderma underwent two operations separately under general anesthesia. We
      used Hollister Skin Gel to fix the endotracheal tube. This gel helped prevent the
      irritation associated with the application and removal of adhesives. The patient
      became severely hypothermic during the first operation. Fortunately, the
      intraoperative body temperature could be maintained at a normal level during the
      second operation with the use of a forced-air warming system. Careful
      perioperative consideration is required for the fixation of endotracheal tubes
      and the management of body temperature in patients with non-bullous congenital
      ichthyosiform erythroderma.

PMID- 14733088
TI  - [Spinal anesthesia in a patient with hemiparesis after poliomyelitis].
AB  - A seventy-year-old man who underwent transurethral resection of the prostate (TUR
      P), had carried over the palsy after poliomyelitis inflicted at one year of age.
      Spinal anesthesia using with 7 mg of hyperbaric tetracaine with dextrose solution
      was performed for this surgery. The running pressure of D-sorbitol solution was
      50 cmH2O during the operation. The operation time was 41 minutes and the balance
      of running water was -200 ml. After this TUR-P, there was no progression of his
      palsy, muscle atrophy or no aggravation of autonomic system immediately after the
      operation, 3 months later and 6 months later, respectively. This case suggests
      that spinal anesthesia can be applied in post-poliomyelitis patients. The
      perioperative maintenance of electrolyte control for endoscopic surgery with
      water running is more important than anesthetic procedure itself in this case.

PMID- 14733089
TI  - [Simulation analysis of estimated effect-site concentrations of propofol and
      fentanyl administered by a TCI system for other drugs].
AB  - BACKGROUND: We experienced a case of inadequate sedation because of inappropriate
      use of TCI system for fentanyl. METHODS: We evaluated the blood and effect-site
      concentrations of propofol and fentanyl calculated by a pharmacokinetic
      simulation model in which the administration of one drug was managed with target
      controlled infusion pump set for another drug. RESULTS: In case propofol was
      administered with an effect-site-steering TCI system for fentanyl, the blood
      concentration of propofol increased within the first few minutes, especially
      immediately after starting the infusion, decreased for the next 10 minutes, and
      then was stabilized at a level of 0.7 times the target concentration. When
      fentanyl was administered with a blood-steering TCI for propofol, the calculated
      blood concentration of fentanyl was almost equal to the target concentration in
      the first few minutes, and then gradually increased until reaching 2.21 times the
      target concentration, at 240 minutes. Furthermore, the propofol concentration and
      the fentanyl concentration showed small differences between the target and
      calculated concentrations when the infusion time was not so long. CONCLUSIONS:
      When the administration time is short, the anesthesiologist must be aware of the
      difficulty in distinguishing the human error of choosing one drug for the TCI
      system for another drug.

PMID- 14733090
TI  - [Plate-rack as a pillow for endotracheal intubation].
AB  - Since we began to use a plate-rack as a pillow for adult endotracheal intubation,
      we can intubate more smoothly than we did with a circular sponge-made pillow
      previously. A pillow for endotracheal intubation must have two characteristics
      for smooth endotracheal intubation. First, it must be able to establish patient's
      head position suitable for endotracheal intubation. Second, it must not permit
      patient's head and neck to move at the time of endotracheal intubation. And it
      must be set to patient's head comfortably. This plate-rack can answer all of
      them. Particularly, we can do endotracheal intubation without neck extension,
      with patient's head on the upper horizontal bar of the plate-rack. Neck extension
      might cause worse visualization of the vocal cord and cervical spinal cord
      injury.

PMID- 14733091
TI  - [Diagnosis and surgical treatment for small-sized peripheral lung cancer].
AB  - Small-sized peripheral lung cancers have been detected more frequently as a
      result of recent developments in diagnostic imaging including high-resolution
      computed tomography (HRCT). Although the diagnosis of small-sized peripheral lung
      cancers is difficult, it makes an adequate diagnosis possible using
      transbronchial fine needle aspiration cytology or a new thin-type bronchoscope.
      Surgical treatment using mini-thoracotomy or video-assisted thoracic surgery is
      effective for early stage small-sized peripheral lung cancers. Lesser resection
      of lung cancer may provide many benefits to patients, such as preserving vital
      lung tissue and providing the chance for further resection if a second primary
      lung cancer develops, however, lobectomy with systematic hilar and mediastinal
      lymph node dissection should remain the standard surgical treatment, and an
      intentional limited resection should be adopted for very limited patients with a
      definitive early stage because of recurrence rates.

PMID- 14733092
TI  - [A rational approach of limited resection for small peripheral lung
      adenocarcinoma with curative intent; analyses of multiple primary
      adenocarcinomas].
AB  - Hundred and forty-one small peripheral adenocarcinomas 2 cm or less in diameter
      were retrospectively studied to determine the rationale of limited resection with
      curative intent. We used a conventional computed tomography (CT) which used 2.5
      mm thick sections to examine only the main tumor during from March 1985 to May
      1999 and a spiral CT which produced 2.5 mm thick sections of the entire lung
      field during from June 1999 to July 2003. The incidence of small peripheral
      adenocarcinoma significantly increased from 12.6% to 29.1%, suggesting an
      increase in the rate of detection with spiral CTs. During the spiral CT era, the
      percentage of females, pathological stage I a tumors, predominant ground-glass
      opacity (GGO) tumors and limited resection were significantly higher. The
      incidence of multiple adenocarcinomas 2 cm or less in diameter significantly
      increased 2.6% to 14.1%. It increases to 21.9% in small adenocarcinomas and 63.6%
      in predominant GGO type, when minute GGO lesion which have been followed in 5
      patients by a watch and wait policy would be bronchioloalveolar carcinoma (BAC).
      In conclusion, a paradigm shift of the treatment for small peripheral
      adenocarcinoma should be warrant, because localized BAC as noninvasive cancer is
      not rare and often found as multiple BACs.

PMID- 14733093
TI  - [Sentinel node biopsy for staging of small peripheral lung cancer].
AB  - Is it possible to choose between limited lymph node sampling and systematic
      lymphadenectomy from the distribution of sentinel lymph nodes in patients with
      small lung cancer less than 2 cm in diameter? METHODS: Twenty-four patients with
      cN0M0 lung cancer less than 2 cm in diameter were enrolled. A radioisotope tracer
      (Tc-99 m tin colloid or phyphate) was injected in the vicinity of the tumor
      before surgery under computed tomography (CT) guidance. The radioactivity of each
      resected lymph node was measured separately with a hand-held gamma probe after
      complete tumor resection. Sentinel nodes were identified and the accuracy of
      sentinel node mapping was examined. RESULTS: Successful radionuclide migration
      occurred in 20 of the 24 patients (83.3%). There were 21 N0 patients and 3 N
      positive patients. There was no false-negative case, so the sensitivity and the
      specificity was 100%. The lobar lymph nodes were identified as sentinel nodes
      more frequently than other lymph nodes. CONCLUSION: The sentinel node concept is
      valid in patients with small lung cancer less than 2 cm in diameter. We believe
      that, if sentinel nodes are identified, sentinel node mapping can allow the
      accurate intraoperative diagnosis of pathological N0 status in patients with
      small peripheral lung cancer.

PMID- 14733094
TI  - [Strategy for surgical treatment for small peripheral carcinoma of the lung
      especially on systemic nodal dissection].
AB  - The diagnosis of small-sized (< or = 2 cm) non-small cell lung cancer (NSCLC) has
      increased with the development of computed tomography (CT), whereas unexpected
      extensive mediastinal involvement has been occasionally detected in such a small
      sized lung cancer. We retrospectively analyzed the clinicopathological features
      to determinate the predictors for lymph node involvement in patients with a small
      sized adenocarcinoma. One hundred and eighty one patients who underwent pulmonary
      resection and systematic nodal dissection for a peripheral small-sized adeno
      carcinoma were reviewed. Of these, 24 patients (13.3%) had lymph node
      involvement. These patients were divided into 2 groups according to the existence
      of lymph node involvement, and the predictors for lymph node involvement were
      determined using univariate analysis and multivariate regression analysis.
      Univariate analysis revealed GGOR (ground glass opacity area/tumor area at the
      level of the greatest dimension of the lesion on chest computer tomography) > or
      = 25% (p = 0.0137) and pleural lavage fluid involvement (p = 0.0467) as
      predictors for lymph node involvement. No patients had lymph node involvement if
      their GGOR was higher than 50%. Multivariate regression analysis revealed GGOR >
      or = 25% (p = 0.0274), pleural tags on the lesion on chest CT (p = 0.0138) and
      pleural lavage fluid involvement (p = 0.0415) as predictors. We recommend
      performing systemic nodal dissection even if small peripheral adeno-carcinoma's
      maximal diameter is 20 mm or less. Systemic nodal dissection is unnecessary if
      the patients' GGOR > or = 50% or they do not have pleural tags or pleural lavage
      fluid involvement.

PMID- 14733095
TI  - [Limited resection for small peripheral lung cancer using intraoperative
      pathologic examination].
AB  - From 1996 to 2002, we performed intentional limited resection for small
      peripheral lung cancer using intraoperative pathologic examination. Wedge
      resection was performed in patients who had small peripheral adenocarcinoma (< or
      = 20 mm), suspected of being Noguchi type A or B, and confirmed by intraoperative
      pathologic examination. Extended segmentectomy was performed in the rest of
      patients (tumor diameter < or = 20 mm), and not suspected of being Noguchi type A
      or B. Hilar and mediastinal lymph nodes sampling was performed in this group. If
      lymph node metastasis was detected by the intraoperative pathologic examination,
      the surgical procedures was converted into a lobectomy with lymph node
      dissection. Limited resection was performed in 27 patients, wedge resection in 8,
      and extended segmentectomy in 19. All patients received wedge resection are alive
      without sign of recurrence. In extended segmentectomy, 17 patients are alive with
      no evidence of disease, 1 patient died of non-pulmonary disease, and 1 patient is
      alive with recurrent disease. The overall survival rate at 5 years was 100% in
      wedge resection, 91% in extended segmentectomy, and 79% in standard lobectomy. We
      conclude that limited resection for small peripheral lung cancer using
      intraoperative pathologic examination may be safe and effective procedure.

PMID- 14733096
TI  - [New surgical technique of pulmonary segmentectomy by ultrasonic scalpel and
      absorbable sealing materials].
AB  - We developed new surgical technique of pulmonary segmentectomy by ultrasonic
      scalpel to sever intersegmental pulmonary tissue and absorbable sealing materials
      to cover the cut surface of lung. This method is expected to preserve more
      anatomical lung volume than the segmentectomy with surgical stapler. Two cases of
      post surgical recurrent lung cancer, 3 cases of pulmonary metastasis and 4 cases
      of primary lung cancer were applied this technique to preserve function. Among 3
      materials examined, best result was obtained with polyglycolic acid felt
      (PGAF:Neoveil). PGAF is a very soft and thin (0.15 mm depth) new absorbable
      material that is able to closely adhere to irregular sections of the lung with
      fibrin glue and effectively seals air leakage. Mean chest drainage period after
      surgery in 6 cases with PGAF was 3.3 days. Excellent lung expansion was obtained
      immediately after the surgery and PGAF was disappeared completely on chest CT
      within 1 year. Although the possible superiority of this method is suggested in
      the present study, further comparative study is necessary to clarify the
      advantage of this new technique.

PMID- 14733097
TI  - [Intentional limited resection for small adenocarcinoma with ground-glass opacity
      component more than 50% on computed tomography].
AB  - Fifty-eight patients who had small lung tumors 2 cm or less with ground-glass
      opacity (GGO) component more than 50% on high resolution computed tomography
      (HRCT) underwent intentional limited resection. After bronchioloalveolar
      carcinoma without both active fibroblastic proliferation and invasive sign to the
      stroma was confirmed, limited resection was completed in 50 patients. In 8
      patients, procedure was converted lobectomy because of microscopic invasive sign
      in 4, active fibroblastic proliferation in 2, and other reasons in 2. Unexpected
      invasive sign was found by detailed post-operative examination in 2 cases. Five
      year survival rate was 98% with a mean follow-up period of 48.8 months. A
      limitation of intra-operative diagnosis was revealed and the accuracy of
      diagnosis should be improved by not only intra-operative pathological diagnosis
      but also HRCT images.

PMID- 14733098
TI  - [Clinicopathologic features of small-sized peripheral lung cancer; is intentional
      limited resection appropriate for selected patients?].
AB  - We sought to determine the eligibility of patients with early peripheral lung
      cancer for intentional limited resection. The clinicopathologic features of 103
      patients who underwent lobectomy and mediastinal nodal dissection for early stage
      peripheral lung cancer measuring 2 cm or less in maximum dimension between 1992
      and 2002 were examined retrospectively. The lymph node metastasis and residual
      cancer after thoracoscopic partial resection were analyzed by the following
      categories. Three groups were divided by maximum dimension of the primary lesion
      in the resected specimen; 10 mm or less (n = 11), 15 mm or less (n = 33), and 20
      mm or less (n = 59). Two groups were divided by lesion histology;
      bronchioloalveolar adenocarcinoma (BAC) [n = 42] and invasive lung cancer (n =
      61). Residual cancer was found in the residual lobe after thoracoscopic partial
      resection in 3 of 43 patients who had no diagnosis preoperatively. Their maximum
      dimensions were 15 mm or less. No lymph node metastasis was detected in the
      patients with tumor measuring 10 mm or less, and BAC. Intentional limited
      resection without mediastinal nodal dissection is appropriate for patients with
      tumor measuring 10 mm or less and BAC. Further investigation associated with
      partial resection is necessary.

PMID- 14733099
TI  - [Clinical study on video-assisted thoracic surgical simultaneously stapled
      subsegmentectomy for peripheral lung tumors].
AB  - BACKGROUND: The purpose of this study is to confirm the safety and validity of
      video-assisted thoracic surgical simultaneously stapled subsegmentectomy
      (simultaneously stapling of all subsegmental bronchi and vessels in their natural
      construction). METHODS: The clinicopathologic information of the 10 patients who
      underwent video-assisted thoracic surgical simultaneously stapled
      subsegmentectomy for primary lung cancer (6) and metastatic lung tumor (4) were
      reviewed retrospectively. The patient population consisted of 7 men and 3 women
      with a mean age of 70.2 years. RESULTS: Median operative time was 201 minutes.
      Average blood loss was 76 ml. Mean duration of thoracic drainage was 3 days.
      There was no surgical mortality. Recurrence was diagnosed in 2 of 6 lung cancer
      patients (each of contralateral lung metastasis and brain metastasis), and 1 of 2
      died 26 months after the operation. All patients have been followed for a mean
      period of 30.4 months with no local recurrence. CONCLUSIONS: Video-assisted
      thoracic surgical simultaneously stapled subsegmentectomy is safe and may be an
      acceptable alternative to segmentectomy, and wedge resection for strictly
      selective patients with peripheral lung tumors.

PMID- 14733100
TI  - [The clinicopathological features of peripheral small-sized (2 cm or less)
      squamous cell carcinoma of the lung].
AB  - Recently the diagnosis of peripheral small-sized lung cancers has increased with
      the development of computed tomography. The vast majority of them are
      adenocarcinoma, whereas squamous cell carcinoma is rare. From 1981 to 2002, 1,054
      patients underwent pulmonary resection for primary lung cancer in National
      Nishigunma Hospital. Among of them, 17 patients with peripheral small-sized (2 cm
      or less) squamous cell carcinoma underwent lobectomy and systemic nodal
      dissection were retrospectively reviewed. These were 15 men and 2 women, with a
      mean age of 68 years (range, 56-75). Regarding the pathologic stage, 15 patients
      were classified in stage IA, 1 in IIA, and 1 in IIIA. Among of them, only 1
      patient with n 2 disease died of cancer at 17 months after surgery. Overall 5
      year and 10-year survival rates of this disease were 84.4% and 73.8%,
      respectively. Based on the present data, we conclude that mediastinal nodal
      dissection would be unnecessary in the patients with peripheral small-sized
      squamous cell carcinoma of the lung.

PMID- 14733101
TI  - [In what case can we abbreviate mediastinal lymph nodes dissection of peripheral
      small-sized lung cancer?].
AB  - We analyzed 723 cases of non small cell lung cancer (459 adenocarcinomas and 264
      squamous cell carcinomas) from the view point of lymph nodes metastases,
      according to histological type, location of cancer and tumor size. METHOD:
      Histological type was adenocarcinoma or squamous cell carcinoma. Location was
      divided into 8 areas [right side; 4 areas, upper lobe (RUL)/middle lobe (RML)/S6
      (RS6)/basal segment of lower lobe (RBS): left side; 4 areas, upper division of
      upper lobe (LUD)/lingula (LLS)/S6 (LS6)/Basal segment of lower lobe (LBS)]. Tumor
      size was divided by centimeters, namely 0.0-1.0 cm, 1.1-2.0 cm, 2.1-3.0 cm, etc..
      RESULTS: Safety size of lung cancer in which we can abbreviate mediastinal lymph
      nodes dissection was as follows. In adenocarcinoma, in RUL/RML/RBS 1.0 cm, in RS6
      2.0 cm, in LUD 1.0 cm, in LLS/LS6/LBS 2.0 cm. In squamous cell carcinoma, in RUL
      1.0 cm, in RML/RS6/RBS 2.0 cm, in LUD 1.0 cm, in LLS/LS6/LBS 2.0 cm. CONCLUSION:
      In 1.0 cm or smaller non small cell lung cancer we might abbreviate mediastinal
      lymph nodes dissection. Moreover, in squamous cell carcinoma of (RML, LLS, right
      or left lower lobe) of 2.0 cm or smaller size, we might abbreviate mediastinal
      lymph nodes dissection.

PMID- 14733102
TI  - [Hypoplastic left heart syndrome].
AB  - Survival of infants born with hypoplastic left heart syndrome (HLHS) has steadily
      improved since Norwood and colleagues first reported a multistage reconstructive
      approach in 1983. Although several experienced centers have achieved operative
      survival for the Norwood procedure between 63-94%, this procedure still remains a
      challenging step with high mortality for many institutions. Despite successful
      reconstructive surgery, most deaths occur in the first 24 to 48 hours after
      surgery due to hemodynamic instability secondary to unpredictable rapid fall in
      pulmonary resistance. Therefore, many efforts to achieve a balanced circulation
      have focused on limiting pulmonary blood flow and increasing systemic oxygen
      delivery. These measures have included reduction in the size of the shunt, use of
      systemic vasodilators, induction of hypoxia and hypercarbia by ventilator
      manipulations and measurement of lactate and mixed venous satulation. Recently RV
      PA shunt using non-valved polytetrafluoroethylene (PTFE) graft was applied as a
      first stage palliation of HLHS to prevent hemodynamic instability associated with
      a classic Norwood procedure. In Okayama University Hospital, there has been no
      hospital and late deaths since 2000.

PMID- 14733103
TI  - [Mucosa-associated lymphoid tissue lymphoma; report of two cases].
AB  - Primary pulmonary malignant lymphoma is a rare disease that is thought to belong
      to a category of malignant lymphomas arising from mucosa-associated lymphoid
      tissue (MALT). We presented 2 cases of MALT lymphoma. Case 1: In a 39-year-old
      woman, an abnormal shadow was detected in chest radiography in the left S3. The
      diagnosis was organizing pneumonia in consequence of the further examination. One
      year after an growing abnormal shadow was detected again, we performed the tumor
      resection with the thoracoscopy in the possibility of malignancy. The
      pathological diagnosis was MALT lymphoma. Case 2: In a 70-year-old man, middle
      lobe syndrome was detected in chest radiography. As a result of the bronchial
      biopsy, the lesion was suspected of MALT lymphoma. Right middle lobectomy was
      performed, and the tumor was diagnosed as a MALT lymphoma histologically. He
      underwent an effective postoperative radiotherapy and has had no evidence of
      recurrence.

PMID- 14733104
TI  - [Mitral valve re-replacement in a patient with occlusion of the left internal
      carotid artery].
AB  - An 83-year-old female patient, who had previously undergone mitral valve
      replacement using bioprosthesis at 15 years ago, presented symptoms of congestive
      heart failure. Mitral valve regurgitation was caused by structural deterioration
      of the bioprosthetic valve, and replacement of the bioprosthesis was indicated.
      Digital subtraction angiography revealed occlusion of the left internal carotid
      artery, which put this patient at high risk to cerebral complications during
      heart valve surgery. Administration of acetazolamide induced a marked decrease in
      the blood flow in the left cerebral hemisphere. Re-replacement of the mitral
      valve was successfully performed under high-flow cardiopulmonary bypass. Intra
      aortic balloon pumping produced pulsatile blood flow with a peak pressure of 90
      100 mmHg during the cardiopulmonary bypass. She recovered after surgery with no
      neurological complication. We believe the pulsatile cerebral perfusion produced
      by the intra-aortic balloon pumping with high-flow cardiopulmonary bypass was
      effective for preventing cerebral complications in this patient with internal
      carotid artery occlusion.

PMID- 14733105
TI  - [Double valve replacement for infective endocarditis following osteomyelitis;
      report of two cases].
AB  - Infective endocarditis(IE) is relatively common but it is lethal complication of
      osteomyelitis. We report the case of 2 patients who had been diagnosed as IE
      during their conservative therapy of osteomyelitis. Both of the patients had been
      admitted because of severe back pain. Then IE was revealed from congestive heart
      failure and/or persistent fever. As several times of echocardiogram showed the
      progression of valvular lesion despite their antibiotic therapies, they underwent
      the operation of aortic and mitral valve replacements. On bacteremia-related
      disease like osteomyelitis, high index of suspicion and early diagnosis of IE are
      essential to its successful treatment.

PMID- 14733106
TI  - [Clinical usefulness of a dual L/N-type Ca2+ channel blocker, cilnidipine, in
      patients with chronic heart failure: assessment with 123I-MIBG myocardial
      scintigraphy].
AB  - Sympathetic nerve system is activated as a compensatory mechanism in heart
      failure. However, excessive activation of sympathetic nerve system deteriorates
      disease state. Sympathetic nerve system can be suppressed with N-type Ca2+
      channel blocker. An antihypertensive drug, cilnidipine, is a dual L/N-type Ca2+
      channel blocker. We studies usefulness of cilnidipine in treating with chronic
      heart failure with 123I-MIBG myocardial scintigraphy. We enrolled 24 patients
      with stable chronic heart failure. Twelve patients were treated with ACE
      inhibitors, diuretics and cardiotonics (control group), and the other 12 patients
      were treated with ACE-inhibitors, diuretics, cardiotonics and cilnidipine
      (cilnidipine group). We examined blood pressure, heart rate, norepinephrine
      level, brain natriuretic peptide (BNP) level, cardiothoracic ratio on chest X
      ray, ejection fraction of left ventricle on two-dimensional echocardiography,
      count rate of heart to mediastinum (H/M) and washout rate (WOR) on 123I-MIBG
      myocardial scintigraphy before and six months after medication. Symptom was
      improved in 8 patients in the control group and 10 patients in the cilnidipine
      group after medication. And another parameters were also improved in the both
      groups after medication. However the degree of change in blood pressure (mmHg)
      was 21.2 +/- 8.0 in the cilnidipine group and 10.8 +/- 9.1 in the control group,
      that in heart rate (/min) was 24.1 +/- 6.8 and 16.2 +/- 11.0, that in BNP level
      (pg/ml) was 65.2 +/- 12.0 and 42.8 +/- 11.1, that in H/M was 0.30 +/- 0.08 and
      0.19 +/- 0.09, that in WOR was 19.4 +/- 5.6 and 12.2 +/- 7.0, respectively. And
      the degree of these changes were larger in the cilnidipine group (p < 0.05).
      These findings suggested that cilnidipine, a dual L/N-type Ca2+ channel blocker,
      might be useful in treating with chronic heart failure.

PMID- 14733107
TI  - [Assessment of therapeutic effect in acute myocardial infarction using
      early/delayed images of 123I-BMIPP myocardial scintigraphy].
AB  - This study was aimed at analyzing the discordance between the initial and late
      scintigraphic images in patients with acute myocardial infarction (AMI), and
      utilizing the data obtained for the treatment of AMI patients. Ninety-one
      patients with a history of the first episode of AMI were enrolled as subjects for
      this study. Emergency coronary angiography was performed in all the patients and
      left ventriculography (LVG) was carried out subsequently. 123I-BMIPP myocardial
      scintigraphy was performed to obtain initial images (BMi) and delayed images at 4
      hours (BMd). Scintigraphy was performed a mean of 6 days after the onset of AMI
      in the patients. The subjects were classified into three groups according to the
      scintigraphic data. Quantitative gated single photon emission computed tomography
      (SPECT) with 99mTc-sestamibi (MIBI) was also conducted one month and 6 months
      later in all the patients. Discordance was observed in 51% of the patients. Left
      ventricular volume based on the quantitative gated SPECT (QGS) data at one month
      and 6 months after myocardial scintigraphy was significantly smaller in the
      washout group than in the other two groups. There was no significant change in LV
      volume measured at 6 months as compared to that measured at one month in the
      washout group. Significant increases in LVEDVI and LVESVI were observed over time
      in the no discordance group. In the fill-in group, the LV volume at one month was
      significantly higher than that in the washout group, but no significant change
      with time was observed. During the subacute stage of myocardial infarction,
      discordance is often seen between initial and late BMIPP-myocardial-scintigraphic
      images. The presence of such discordance, and analysis of its pattern, may be
      useful in predicting the cardiac function in these patients during the chronic
      phase of this disease.

PMID- 14733108
TI  - [A case report of distant lymph nodes metastases from prostate cancer imaged with
      201Tl and 99mTc-MIBI].
AB  - Prostate cancer most often metastases to regional lymph nodes and bones by
      hematogeneous or lymphatic spread. The authors present a rare case of metastatic
      prostate cancer to supradiaphragmatic lymph nodes that were detected on 201Tl and
      99mTc-MIBI imaging and confirmed on a CT scan. An 81-yr-old man with bilateral
      painful cervical lymphadenopathies was referred to our hospital with suspected
      thyroid cancer. The US and thyroid scan indicated no abnormalities in his thyroid
      gland. Both 201Tl and 99mTc-MIBI scans showed multiple areas of abnormally
      increased radioactivity in both supraclavicular, anterior mediastinum, and
      bilateral hilar regions. A CT scan also revealed multiple lymphadenopatheis in
      the same regions as radionuclide scans. Prostate cancer was diagnosed from the
      results of immunohistochemical staining for PSA examination of a biopsy specimen
      of the mediastinal lymph node. The serum PSA concentration was markedly elevated
      at 490 ng/ml (normal, < 40 ng/ml). Both 99mTc-HMDP bone and 67Ga scans were
      normal. All supradiaphragmatic lymph nodes on CT images disappeared 2 months
      after subcapsular orchiectomy and endocrine treatment with Bicalutamide.
      Metastatic prostate cancer should be considered when metastatic adenocarcinoma is
      discovered in the supraclavicular lymph nodes of elder men.

PMID- 14733109
TI  - [Clinical evaluation of 111In-oxine-labeled platelet and 99mTc-HSA-D
      scintigraphies in Kasabach-Meritte syndrome associated with anterior mediastinal
      hemangioma: case report].
AB  - A 12-year-old girl presented with Kasabach-Meritte syndrome associated with
      anterior mediastinal hemangioma. 111In-oxine-labeled platelet scintigraphy and
      99mTc-HSA-D scintigraphy were very useful for the diagnosis and evaluation of
      this condition.

PMID- 14733110
TI  - [Microeconomics of introduction of a PET system based on the revised Japanese
      National Insurance reimbursement system].
AB  - It is crucial to evaluate an annual balance before-hand when an institution
      installs a PET system because the revised Japanese national insurance
      reimbursement system set the cost of a FDG PET study as 75,000 yen. A break-even
      point was calculated in an 8-hour or a 24-hour operation of a PET system, based
      on the total costs reported. The break-even points were as follows: 13.4, 17.7,
      22.1 studies per day for the 1 cyclotron-1 PET camera, 1 cyclotron-2 PET cameras,
      1 cyclotron-3 PET cameras system, respectively, in an ordinary PET system
      operation of 8 hours. The break-even points were 19.9, 25.5, 31.2 studies per day
      for the 1 cyclotron-1 PET camera, 1 cyclotron-2 PET cameras, 1 cyclotron-3 PET
      cameras system, respectively, in a full PET system operation of 24 hours. The
      results indicate no profit would accrue in an ordinary PET system operation of 8
      hours. The annual profit and break-even point for the total cost including the
      initial investment would be respectively 530 million yen and 2.8 years in a 24
      hour operation with 1 cyclotron-3 PET cameras system.

PMID- 14733111
TI  - [The present status of I-131 therapy for Graves' hyperthyroidism in Japan (survey
      by questionnaire)].
AB  - A survey on the I-131 therapy of Graves' hyperthyroidism was undertaken by
      questionnaire in 1,246 hospitals of Japan. One thousand and ninety seven of them
      (88.0%) responded to the questionnaire. In this paper, we report the results and
      analysis of the replies to the questionnaire. In the 121 hospitals (11.03%) of
      the respondents, I-131 therapy is being performed for Graves' hyperthyroidism. A
      gradual increase was observed in the annual number of I-131 treated Graves'
      disease patients during the period of 1998-2001, from 1,740 to 2,484. I-131
      treatment was selected mainly for the cases with side effects from antithyroid
      drug (ATD) therapy, followed by the cases with complication of heart or hepatic
      diseases, recurrences of hyperthyroidism after surgery, radioiodine treatment,
      and long-term ATD treatment. The 41% of respondents used I-131 in order to
      restore euthyroidism, 34% aimed for hyperthyroidism and 41% used the dose
      properly between the two according to the patients. Administration dosage of I
      131 was estimated mainly on the basis of thyroid uptake and volume in 93% of the
      respondents and 48% calculated the radiation dose by also determining the
      effective half-life in the thyroid gland. Thyroid size was estimated by
      scintigram (51%), US (33%), CT (22%) and palpation (12%). ATD treatment was used
      before I-131 administration by 70% of the respondents and 34% after radioiodine
      therapy. A low-iodine diet was given to the patients for a week (46%) or two
      weeks (47%) before I-131 administration. However, after treatment only 46% of the
      respondents continued low-iodine diet for a week.

PMID- 14733112
TI  - [A study on pulmonary tuberculosis retreatment cases].
AB  - OBJECTIVE: To investigate the factors leading to the retreatment for
      tuberculosis. MATERIALS: Forty-seven retreatment cases with pulmonary
      tuberculosis, who were discharged from the National Chiba Higashi Hospital from
      2000 to 2002. METHODS: Data on all retreatment cases were studied as to the
      condition of the original treatment and factors leading to the retreatment.
      RESULTS: Of the 47 cases, 33 cases received the original treatment in our
      hospital. Of the 33 cases, 24 cases were relapsed cases and 9 cases were
      defaulters. Most relapsed cases were male aged 50s and 12 cases (50%) were
      jobless. As the factors leading to retreatment, the delay in the negative
      conversion of sputum culture accounted for 11 cases (45.8%) out of 24 cases. No
      specific factors were found in three cases (12.5%). Among the defaulters, no bias
      was seen as to age and occupation of cases, but all the cases were male, and they
      defaulted during the maintenance phase of treatment at the out-patient
      department. CONSIDERATION: The delay in the negative conversion of sputum culture
      was the main factor relating to the relapse. Diabetes mellitus (DM) is one of the
      factors leading to the relapse, but many factors were observed in DM patients.
      Male cases aged 50s had many factors leading to the relapse. An intensive
      management for out-patients and involvement of welfare department aiming at the
      completion of treatment for the socially vulnerable groups might be necessary as
      the measure to prevent defaulting. CONCLUSION: The delay in the negative
      conversion of sputum culture was the main factor leading to relapse, and
      intensive management for out-patients aiming at the completion of treatment is
      necessary to prevent the defaulting.

PMID- 14733113
TI  - [Environmental factors relating to a mass outbreak of tuberculosis in a junior
      high school].
AB  - OBJECTIVE: To clarify environmental factors relating to a mass outbreak of
      tuberculosis. METHODS: A 15-year old girl, a third-grade student of a junior high
      school (the index case) was found to have smear-positive cavitary pulmonary
      tuberculosis. Among 718 subjects who underwent contacts investigation, the rates
      of infection and cases among different exposure groups were compared. The
      ventilation rate within the room of the junior high school was analyzed using
      sulfur hexafluoride (SF6) as the tracer gas. RESULTS: Up to 56 months after the
      detection of the index case, a total of 34 tuberculosis patients were newly
      diagnosed, and 155 persons were subjected to chemoprophylaxis. The rates of
      infection were 90.0% among homeroom classmates and 60.8% among other classmates,
      respectively. Out of the subjects who had only indirect contact with the index
      case, 11 patients were diagnosed. Most of the windows of the building were of the
      fixed sash type, permitting only low ventilation ranging from about 1.6 to 1.8
      room air change per hour. When sliding doors of the room were opened, the SF6
      concentration in the room was rapidly mixed up with that in the passage.
      CONCLUSION: Low ventilation of the room and overcrowding contributed to the high
      infection rate among homeroom classmates. Infectious droplet nuclei spread to the
      passage at recess. The homeroom of the index case was located in front of the
      building's entrance. The index case used some common rooms of the building. In
      addition to these environmental factors, other factors, especially the high
      infectiousness of the index case also contributed to the mass outbreak.

PMID- 14733114
TI  - [Fluctuation in the ratio between drug-resistant and -susceptible M. tuberculosis
      bacilli which were isolated from patients with prolonged anti-tuberculosis
      treatment].
AB  - PURPOSE: In this study, we examined the fluctuation in the ratio between strains
      of tuberculosis bacilli resistant and susceptible to the anti-tuberculosis drugs.
      MATERIAL & METHOD: We selected the cases in which the bacilli acquired drug
      resistance during the therapy and the cases in which drug resistance was
      fluctuating during prolonged anti-tuberculosis treatment. We selected the
      isolates throughout the medication period, and the selected isolates were
      separated into respective single colonies. Then we measured the minimal
      inhibitory concentration (MIC) for each colony by microdilution test for M.
      tuberculosis complex, BrothMIC MTB-1 (Kyokuto Pharmaceutical Inc., Tokyo).
      RESULTS: Five patients were eligible for analysis because their medical histories
      were clearly recorded and drug resistance changed during the course. The MIC of
      19 isolates, 202 colonies were measured. Isolates with coexisting drug-resistant
      and -susceptible colonies were detected in 2 patients. From these results, we
      considered that the fluctuation in the ratio between drug-resistant and 
      susceptible bacilli changes with the progression of anti-tuberculosis medication.
      CONCLUSION: We showed in this article that the drug-resistant bacilli increased
      rapidly when the strains acquired the drug resistance during medication, and when
      the administration of particular anti-tuberculosis drug was stopped, the
      susceptible bacilli seemed to increase gradually. However, the strain immediately
      became fully drug-resistant when the particular antibacterial drug was
      readministered.

PMID- 14733115
TI  - [Infants and children who developed tuberculosis following contacts
      investigation].
AB  - OBJECT: Reevaluating the important points in tuberculosis contacts investigation.
      SUBJECT AND METHODS: We retrospectively examined the medical charts of 25 infants
      and children who developed tuberculosis following contacts investigation.
      RESULTS: In thirteen patients, diagnosis of infection was missed, and three of
      five infants less than one year old suffered from meningitis or military
      tuberculosis while they were waiting the next examination. Three patients were
      not indicated preventive treatment despite of induration of 5 mm or more in
      tuberculin skin test. Other twelve patients including five infants less than one
      year old were diagnosed to have tuberculosis infection and started preventive
      therapy, however, tuberculosis developed in 10 patients while taking the
      medicine, and in two patients probably because of defaulting from taking the
      medicine. CONCLUSION: These results suggest that the contacts investigation have
      to be done promptly and be flexible based on age of contacts, evaluation of
      tuberculin skin test results and radiographic findings in order to reduce the
      disease further.

PMID- 14733116
TI  - [A case of primary nasopharyngeal tuberculosis].
AB  - BACKGROUND: Although the prevalence of nasopharyngeal tuberculosis has decreased
      after the wide use of anti-tuberculous agents, recently the number of reports
      with the disease has slightly increased in accordance with advances in the
      diagnostic tools. A case of nasopharyngeal tuberculosis without any tuberculous
      lesions in other organs (primary nasopharyngeal tuberculosis) was reported. CASE
      REPORT: A 74-year-old female complained of vertigo and cervical masses, and naso
      pharygo-laryngoscopy disclosed a polypoid lesion on her nasopharynx. The biopsy
      from the mass revealed epithelioid cell granulomas with caseous necrosis and
      multinucleated giant cells consistent with tuberculosis. Since there were no
      tuberculous lesions in other organs except cervical lymph nodes in clinical
      examinations, we diagnosed the case as primary nasopharyngeal tuberculosis with
      tuberculous cervical lymphadenitis. The nasopharyngeal manifestation disappeared
      after four months chemotherapy with INH, RFP and EB. DISCUSSION: Most reported
      case of nasopharyngeal tuberculosis were in the young age group. A rare case of
      old woman complicated with cervical tuberculous lymphadenitis was reported.

PMID- 14733117
TI  - [Pulmonary aspergilloma, diagnosis and treatment].
AB  - Pulmonary aspergilloma is a saprophytic form of aspergillosis, and the diagnosis
      is usually based on radiological findings such as thickened cavitary wall and
      fungus ball, and on positive serum antibody. Up to 58% of the patients with
      aspergilloma in Japan have medical history of tuberculosis. Serum anti
      Aspergillus antigen is almost always positive in aspergilloma patients but
      aspergillus antigen is usually negative. Massive hemoptysis can be a fatal
      complication of aspergilloma, and the most common complication was respiratory
      failure according to our study. Surgical resection is the only promising
      intervention to cure the aspergilloma, however, low pulmonary function does not
      allow operation. Antifungal treatment is chosen for those who are out of
      operation indication, but the efficacy of antifungal treatment against
      aspergilloma is controversial. Some patients with aspergilloma show progressive
      form, and we define such aspergillosis as CNPA, chronic necrotizing
      aspergillosis, although the original entity of CNPA by Binder et al. is
      different. We make a diagnosis of CNPA only if all the following entity meets, 1;
      progressive shadows in radiological findings regardless of the presence of
      aspergilloma, 2; have some symptoms such as cough, sputum, hemosputum, hemoptysis
      or fever, 3; proof of Aspergillus attribution by mycological or pathological
      examination, 4; positive systemic inflammatory reaction, 5; neglect of other
      etiology of pulmonary diseases. Since CNPA is usually progressive, patients with
      CNPA should be treated with antifungals.

PMID- 14733118
TI  - [Review of 26 patients operated on for primary hyperparathyroidism].
AB  - The traditional surgical approach for primary hyperparathyroidism (PHP) is
      routine bilateral neck exploration. At Saiseikai Utsunomiya Hospital, however,
      unilateral exploration, and the direct resection of one gland is performed if
      single gland enlargement is suspected, based on the findings of several
      preoperative localization procedures. Here, we reviewed 26 patients who underwent
      single gland operations for PHP at our institution between 1993 and 2001. The 26
      patients (21 women and 5 men) ranged in age from 20 to 79 years (mean, 54.8
      years). None of the patients had multiple endocrine neoplasia (MEN), familial
      hypercalcemia, or malignant tumors. At least three preoperative localization
      procedures, such as ultrasonography, computed tomography, thallium technetium
      scanning, 99mTc sestamibi scintigraphy, or magnetic resonance imaging, were
      performed in each patient. A parathyroidectomy was then performed under general
      anesthesia. Contralateral exploration was not routinely performed. In addition,
      an intraoperative biopsy of the other glands was not performed. The following
      data were retrospectively collected in all patients: serum calcium, and the HS
      PTH at one month and 6 months after the parathyroidectomy. All patients were
      normocalcemic, and the serum HS-PTH concentration significantly decreased in all
      patients after this operation. Patients were divided into two groups (adenoma
      group, n = 16; hyperplasia group, n = 6) and the data was analyzed according to
      the histological and pathological diagnosis. In both pathological groups, all
      patients were normocalcemic and the serum HS-PTH concentration was significantly
      lower after surgery. The serum HS-PTH concentration showed no significant
      difference between the adenoma group and the hyperplasia group at 6 months after
      surgery. No complications, including recurrent laryngeal nerve palsy or permanent
      hypocalcemia, were observed after surgery. In conclusion, if a single gland
      disease is suspected based on the findings of multiple preoperative localization
      procedures, resection of the enlarged gland alone appears to provide good results
      for the treatment of either adenoma or hyperplasia resulting in PHP. In addition,
      this procedure also reduces the occurrence of postoperative hypocalcemia, because
      the normal glands are not injured by the biopsy procedures.

PMID- 14733119
TI  - [Nocturnal pulse oximetry diagnosis for screening pediatric obstructive sleep
      apnea syndrome].
AB  - We evaluated the diagnostic value of pulse oximetry during sleep in pediatric
      obstructive sleep apnea syndrome (OSAS) caused by adenoid-tonsil hypertrophy.
      Subjects were 22 healthy children free of symptoms such as snoring, sleep apnea
      and oral breathing and 163 children suspected of OSAS with snoring or sleep
      apnea. Subjects were measured for percutaneous oxygen saturation (SpO2) during
      sleep. Of those with suspected OSAS, 69 underwent adenotonsillectomy and were
      measured for SpO2, both pre- and postoperatively, then pre- and postoperative
      measurements were compared. After measurement, we analyzed three parameters:
      lowest saturation (LSpO2), the desaturation index, and total desaturation
      duration under 95% (TDD95). Few abnormal findings were seen in healthy children.
      We calculated the mean and standard deviation (SD) of each parameter and set
      borderlines of mean-2SD for LSpO2 and mean + 2SD for ODI and TDD95. With these
      borderlines, 105 children for LSpO2, 75 for ODI and 76 for TDD 95 were judged to
      be normal among the 163 with suspected OSAS. Histograms showed that the mode of
      each parameter was situated near the borderline. Comparison between pre- and
      postoperative measurements showed that the effect of the surgery strongly
      correlated with preoperative measurement in patients undergoing surgery. Assuming
      that a patient with postoperative improvement is positive, we calculated
      sensitivity and specificity for each borderline measurement. We found that if
      success is 100%, the borderline should be 87% for LSpO2, 3.5 for ODI, and 30.0
      for TDD95. If success exceeds 90%, the borderline should be 90% for LSpO2, 2.0
      for ODI, and 7.0 for TDD95. We therefore conclude that measurement of SpO2 during
      sleep is useful in screening for pediatric OSAS.

PMID- 14733120
TI  - [Effectiveness of intentional lateralization of the tympanic membrane to promote
      drainage of a large intracranial cholesterol cyst].
AB  - A 57-year-old male presented with headache and cerebellar symptoms. A magnetic
      resonance image demonstrated that the brain stem and the cerebellum were
      compressed by a large intracranial cholesterol cyst. Abundant drainage from the
      cyst into the tympanic cavity following the intentional lateralization of the
      tympanic membrane was very successful in aerating the cyst via the tympanic
      cavity, resulting in the eradication of the cyst. Our new method is recommended
      as a curative treatment for large intracranial cholesterol cysts because of its
      limited surgical stress and high radicality.

PMID- 14733121
TI  - [A case of malignant peripheral nerve sheath tumor requiring thoracotomy].
AB  - A 32-year-old woman with Von Recklinghausen's disease had a malignant peripheral
      nerve sheath tumor that had progressed to malignancy from a neurofibroma arising
      in the left phrenic nerve. The tumor was removed combining a neck incision and
      thoracotomy. It should be more widely recognized that neurofibroma associated
      with Von Recklinghausen's disease may progress to malignancy. Primary treatment
      requires a broad surgical excision to obtain an adequate margin.

PMID- 14733122
TI  - [Immunohistochemical study for monoamine neurons in the brain of unilateral inner
      ear impaired rats].
AB  - Patients with inner ear impairment have complaints of vertigo and also
      occasionally depression. The present study was undertaken in order to evaluate
      changes in monoamines which have reportedly been closely related to depression,
      using cisplatin-induced unilateral inner-ear impaired rats. A dose of 0.5 mg/kg
      of cisplatin was injected into the right tympanic cavity under pentobarbital Na+
      anesthesia. One or two weeks later, animals were fixed with paraformaldehyde, and
      thereafter immunohistochemical stainings for monoamine-containing cells in the
      brain were carried out. To visualize 5-hydroxytryptamine (5-HT), noradrenaline
      (NA) and dopamine (DA) neurons, we used mouse antibodies against 5-HT, NA, and DA
      syntheses, i.e., tryptophan hydroxylase (TRH), tyrosine hydroxylase (TH) and
      dopamine-beta-hydroxylase (DBH). The number of TRH immunoreactive neurons
      significantly decreased in the lateral dorsal raphe nucleus of the ipsilateral
      side when compared with the contralateral side. The number of DA neurons, which
      were immunoreactive to TH, but not to DBH, significantly decreased in the
      hypothalamus of the ipsilateral side. The number of NA neurons which were
      immunoreactive to both TH and DBH significantly decreased in the locus coeruleus
      and ventral lateral pons of the ipsilateral side. An additional control study
      with saline-injected rats showed a lack of differences in monoamine syntheses
      between the injected and contralateral sides, the expressions of the synthesis on
      both sides being similar to that obtained in the contralateral side in cisplatin
      injected rats. These results indicated the decreases in monoamine syntheses at
      the ipsilateral side only in the cisplatin-administered rats. We conclude that
      inner ear impairment may diminish the ipsilateral amount of monoamines in the
      brain but not the cotralateral, possibly inducing a vestibular compensation such
      as an upregulation of monoamine receptors.

PMID- 14733123
TI  - [Common achievement tests in dental education].

PMID- 14733125
TI  - [Influence of occlusal contacts of implant on adjacent teeth and antagonists
      displacements].
AB  - This study examined the optimum occlusal contacts of implant prostheses to
      maintain good oral condition after treatment. Three subjects who had two
      contiguously missing teeth (first and second molars) were selected. The
      displacement path of the implant, the adjacent tooth and the antagonistic tooth
      during clenching were measured using the type M-3 three-dimensional tooth
      displacement transducer. The occlusal contacts of implant prostheses changed
      according to the following four conditions. A contact: the inner inclination of
      the upper buccal cusp, B contact: the inner inclination of the upper lingual
      cusp, C contact: the outer inclination of the upper lingual cusp, and ABC
      contact: including the above three contacts. The measurements were performed at
      least six months after implant surgery. In each subject, the implants and the
      adjacent teeth were not affected by the change of the occlusal contact of the
      implant prosthesis, but the opposing teeth were affected. In the case of
      implantation in the lower side, the opposing tooth displaced in the buccal
      direction with A contact and C contact, which was a different direction to that
      of the natural tooth. The antagonist with B contact displaced in the lingual
      direction, which was the same direction as that of the natural tooth. The
      antagonist with ABC contact displaced in the lingual or buccal direction. It is
      concluded that the occlusal adjustment of implants needs much care: in the case
      of only A contact or C contact, non-physiological distortion might occur in
      periodontal tissues of the opposing teeth of the implant.

PMID- 14733126
TI  - [Incident and accident reports in Tokyo Medical and Dental University Dental
      Hospital (FY 2001-2002)].
AB  - In 2002, the Dental Hospital of Tokyo Medical and Dental University set up a
      working group for risk management. This working group analyzed 225 incident and
      accident reports submitted to the hospital in 2001 and 2002. Each report was
      analyzed with regard to "type," "place," "reporter," "severity," and "cause" in
      order to diagnose hospital safety and prevent future incidents and accidents. The
      cause of incidents and accidents was analyzed using the SHEL model, where S
      stands for Software, H for Hardware, E for Environment, and L for Liveware. The
      severity of the consequence was classified into 6 levels, where level 0 = "error
      not applied," level 1 = "not affected," level 2 = "watch and see or additional
      test," level 3 = "treatment," level 4 = "aftereffect," and level 5 = "death." The
      incidents and accidents judged to have potentially high risk were given a score
      of "+H," irrespective of the level. The results of the analyses revealed that
      most of the incidents and accidents happened in "wards," "operation rooms," and
      "oral surgery clinics." This is probably because the incident and accident
      reporting system is well established by nurses working in these clinics.
      Additional analysis revealed that most of the reports were written and submitted
      by nurses. The frequencies of "treatment procedure," "misuse of dental
      instruments," "mis-prescription," "falling down" and "needlestick" related
      incidents and accidents were the highest and were caused mainly by L and S. There
      were only 3 accidents above level 4, however, less severe cases were given a
      score of +H due to the high potential risk involved.

PMID- 14733124
TI  - [Usefulness of CT and MR imaging in the diagnosis of soft tissue mass lesions of
      the oral region].

PMID- 14733127
TI  - [Dysphagia severity scale].
AB  - A simple, broadly applicable, standardized dysphagia severity scale would be
      useful to standardize dysphagia evaluations, to monitor recovery and efficacy of
      treatment and to study the consequences of dysphagia. We developed a global
      Dysphagia Severity Scale (DSS) from videofluorographic swallowing studies which
      included subjective clinical ratings of functional swallowing. We rated laryngeal
      penetration/aspiration (P/A) and pharyngeal retention (PR), and then assessed
      methods for scoring severity of P/A and PR and for combining them in a global
      scale. Each method was tested by correlation with overall clinical severity
      ratings. The highest correlations were found by: 1) scoring P/A based on which
      foods were aspirated (no aspiration or penetration; penetration only; thin liquid
      aspiration; thick liquid, pudding, or chewed solid food aspiration; 2) scoring PR
      based on how much food was retained (none; minimal; moderate; severe); and 3)
      combining P/A and PR by taking the higher of the two scores as the final DSS
      rating. The final global DSS score and the clinical severity rating correlated
      well (r = 0.71). This proposed scale shows promise for rating global dysphagia
      severity.

PMID- 14733128
TI  - [Pathophysiology of vitreous].

PMID- 14733129
TI  - [21st century management of glaucoma].
AB  - According to a recent epidemiological study done in Japan, 2 or 3 million
      Japanese people are thought to be suffering from glaucoma, and 70-80% of them
      have not been examined or diagnosed by ophthalmologists. Therefore, the problem
      is how to find these untreated and undiagnosed people. At present, treatment of
      glaucoma continues to be directed at lowering intraocular pressure to prevent
      progression of glaucomatous optic neuropathy. However, theoretically, there are
      three stages in the prevention of progression of glaucoma. In the first stage,
      diagnosis of glaucoma can be done by genetic examination, before occurrence of
      glaucoma. The MYOCILIN/trabecular meshwork-inducible glucocorticoid response gene
      and the optineurin gene were identified as the genes that cause open angle
      glaucoma. Although some Japanese patients have sequence changes in the myocilin
      gene, there are no apparent specific mutations in Japanese glaucoma patients, in
      the MYOCILIN/TIGR and optineurin genes. Secondary glaucoma such as steroid
      glaucoma, induced by allergic diseases, and neovascular glaucoma, induced by
      retinal circulatory insufficiency, are preventable by improving the causal
      diseases, diabetes and hypertension. The education of doctors and laymen is
      important to reduce the occurrence of diabetes, and hypertension to prevent
      diabetic retinopathy, and retinal vessel occlusion. The second stage in
      preventing progression of glaucoma is to find the disease as early as possible.
      In Japan, a physical examination system is in place for everybody over 40 years
      old, in companies and local districts. Therefore, ocular examination, specially
      non-mydriatic fundus photographs should be taken in these examinations, and the
      film should be evaluated by an ophthalmologist, to search for retinal and optic
      disc abnormalities. Primary open angle glaucoma can be detected through this
      system in early stages. In primary angle closure glaucoma, instruments for
      estimating anterior chamber rapidly and accurately are necessary for the
      diagnosis. There is a special machine which can be handled easily, safely, and
      economically for detecting angle closure glaucoma, has been developed by
      Yamanashi University. This machine might help to reduce the number of angle
      closure glaucoma patients in the world. In the near future, a glaucoma network
      system should be put in place all over Japan. This organization consists of
      central headquarter and local central office. Most hospitals and private offices
      will belong to a local central office, and several glaucoma specialists will work
      in central and local offices. All glaucoma patients will be registered in local
      glaucoma office. The information on glaucoma patients will be communicated in the
      system the through light fiber cables or a satellite system. The patients can ask
      about their own disease through this glaucoma center system. In the third stage
      of glaucoma prevention, progression of glaucomatous optic neuropathy is retarded
      by conventional IOP lowering treatment or neuroprotective drugs. This stage
      compromises rehabilitation of visual function, implant of artificial visual
      systems, and regeneration of retinal ganglion cells(RGC). The disturbances of
      axonal flow in guinea pig optic nerve fibers was demonstrated
      electromicroscopically by quick-freeze, deep-etching method and, the decrease in
      numbers of motor proteins like "Kinesin" "Dynein" and "MAP-1" was shown in guinea
      pig eyes with elevated intraocular pressure by immunohistochemistry. Retinal
      glanglion cells have been isolated and new findings have been reported using this
      RGC culture system. Therefore, new neuroprotective drugs will be developed
      through this culture system.

PMID- 14733130
TI  - [Surgical treatment of complicated retinal detachment].
AB  - Treatment of retinal detachment advanced markedly during the 20th century. The
      surgical approach to rhegmatogenous retinal detachment was first established by
      Joules Gonin, and treatment of traction retinal detachment by vitrectomy was
      developed by Robert Machemer. Although favorable outcomes are obtained in most
      cases of retinal detachment using current vitreoretinal surgical techniques,
      several special types of complicated retinal detachment can be refractory to
      treatment. The biologic mechanism and the strategy for treatment of a complicated
      retinal detachment will be discussed in this lecture. A discrepancy in the length
      between the retina and the outer shell, specifically in the extension of the
      sclera or shortening of the retina, is commonly seen in refractory cases. To
      correct this, shortening of the sclera should be the primary treatment approach.
      Relaxing retinotomy should not be a primary procedure in most cases, since
      retinotomy encourages further shortening of the retina. Equal extension of the
      scleral wall is frequently seen in eyes with Marfan's syndrome, buphthalmos, and
      blue sclera, and the discrepancy is corrected by equal shortening of the sclera
      by encircling and not by focal shortening of the sclera. Unequal extension of the
      sclera occurs in posterior staphyloma in highly myopic eyes, morning glory
      syndrome, and posterior coloboma of the choroid. Focal expansion of the posterior
      sclera should be corrected by placement of a posterior buckle or circumferential
      lamellar scleral resection and shortening in the same quadrant. Circumferential
      surgical shortening of the sclera is also indicated in extreme shortening of the
      retina in congenital retinal folds with persistent fetal vasculature. In cases
      with associated retinal detachment with retinal folds, radial surgical shortening
      of the sclera or radial buckling of the sclera corresponding to the retinal fold
      is indicated, and retinotomy must be avoided. In comparison, in the presence of
      the retinal shortening and folding that develops postnatally in retinopathy of
      prematurity, familial exudative vitreoretinopathy, and incontinentia pigment,
      spontaneous release of the shortening can be expected following surgical removal
      of the preretinal fibrous tissue, and associated encircling procedures can be
      effective in selected cases. Inadequate surgical procedures such as creation of
      multiple iatrogenic retinal breaks to remove extensive subretinal tissue,
      excessive photocoagulation for retinal angiomatous lesions, and inadequate
      indications for vitrectomy to treat a special form of rhegmatogenous retinal
      detachment frequently result in the most complicated form of traction retinal
      detachment. A large circumferential retinotomy is beneficial rather than multiple
      small breaks. Penetrating diathermy through a lamellar scleral flap and
      encircling carries less risk of inducing traction retinal detachment compared
      with excessive photocoagulation. For oral breaks or ciliary epithelial breaks
      commonly seen with blunt ocular trauma or atopic dermatitis, a scleral implant
      more anterior to the extraocular muscle insertion combined with separate
      encircling is safer and more effective than primary vitrectomy.

PMID- 14733131
TI  - [The pathogenesis of vitreoretinal diseases from the standpoint of molecular
      biology].
AB  - It is important to study the pathogenesis in vitreoretinal diseases to develop
      new medical therapy. We investigated the molecular mechanisms underlying the
      genesis of idiopathic macular hole, exudative age-related macular degeneration
      (AMD), and diabetic retinopathy. We observed high levels of chymase and tryptase
      activity in the vitreous humor of patients with idiopathic macular hole. This
      activity was significantly higher than in other vitreoretinal diseases.
      Immunohistochemical study using monkey eyes showed the possibility that Muller
      cells in foveal lesions have properties similar to retinal stem cells.
      Intravitreal injection of chymase induced apoptosis of foveal retinal cells and
      fibrous change of vitreoretinal interface in the macular area. Biochemical study
      using cultured human Muller cells revealed that chymase caused the inhibition of
      growth and the induction of apoptosis in dedifferentiated Muller cells treated
      with basic fibroblast growth factor (bFGF). These findings show that increased
      production of chymase and tryptase in mast cells could be related to the
      pathogenesis of idiopathic macular hole. Oxidative stress and arterosclerosis may
      be the major causes of exudative AMD. Paraoxonase (PON) is a polymorphic protein
      known to prevent oxidation of low-density lipoprotein (LDL). We analyzed PON
      genotypes and found that two types of polymorphism were significantly different
      between patients with AMD and control subjects. We also investigated serum
      oxidized low-density lipoprotein(oxLDL) levels, PON activity, and extracellular
      superoxide dismutase(EC-SOD) levels. All these factors were significantly higher
      in patients with AMD than in controls. Titers of IgA and IgG antibodies against
      chlamydia pneumoniae in the serum of AMD patients were also significantly higher
      than in controls. These results indicate that genetic factors related to PON
      polymorphisms, vascular damage caused by increment of serum oxLDL and malfunction
      of EC-SOD, and chronic inflammation provoked by clamydia pneumoniae infection may
      be involved in the pathogenesis of AMD. Excess accumulation of advanced glycation
      end products(AGEs) has a causative role in the development of diabetic
      complications. We determined the concentrations of three AGEs (pentosidine,
      carboxy-methyllysine, and crossline) and two cytokines (VEGF, IL-6) using ELISA.
      The levels of the three AGEs and two cytokines in the vitreous of patients with
      proliferative diabetic retinopathy(PDR) were significantly higher than in
      controls. The concentrations of VEGF and IL-6 were strongly correlated with the
      level of these AGEs. Cultured human Muller cells expressed both VEGF and IL-6
      mRNA and these expressions were augmented after the treatment of AGEs, while also
      acting as photosensitizers and accelerating the degradation of hyaluronic acid in
      vitro. AGEs may consequently play an important role in the pathogenesis of
      diabetic retinopathy by inducing the production of VEGF and IL-6 in retinal
      Muller cells and the acceleration of vitreous liquefaction.

PMID- 14733132
TI  - [Vitreous and macular diseases].
AB  - We investigated the vitreous in its origin, morphology, metabolism and
      regeneration, and its role in various vitreomacular diseases. Focal vitreous
      liquefaction developed anterior to a laser induced chorioretinal scar in rabbit
      eyes, which suggested that a normal retina is necessary to maintain the integrity
      of the vitreous. We measured levels of hyaluronic acid and of the precursor of
      type II collagen in vitreous samples obtained by vitrectomy. Those levels
      declined with age in women. The precursor of type II collagen was at the same
      level in the samples from vitrectomy and those obtained by fluid air exchange,
      which suggested a persistent secretion of type II collagen into the vitreous
      cavity even after vitrectomy. We found a posterior precortical vitreous pocket in
      human autopsied eyes whose vitreous was stained with fluorescein. Using the same
      methods, we confirmed the presence of intravitreal fibrous membranes in the
      "tractus" in the anterior vitreous. In clinical studies using biomicroscopy,
      observations during surgery, scanning laser ophthalmoscopy, and optical coherence
      tomography (OCT), we clarified the role of premacular vitreous cortex which forms
      the posterior wall of the "pocket" in the premacular membrane and macular hole.
      The premacular vitreous cortex seems to be the main structure of the premacular
      membrane and its contraction may cause macular hole. Ring-shaped proliferation
      tends to develop along the outer margin of the "pocket". OCT demonstrated that
      some diabetic macular edema is caused by traction of the premacular vitreous
      cortex. Vitrectomy appear to be effective for diabetic macular edema by
      eliminating vitreous traction and the accumulated cytokine in the "pocket". The
      retina appears to have a program for vitreous metabolism throughout life,
      including the premacular pocket formation.

PMID- 14733133
TI  - [Relationship between vitrectomy and the morphology and function of the retina].
AB  - Pathological processes in the vitreous will be reflected in the morphology and
      function of the retina, and these processes can originate from sources outside
      the vitreous. The purpose of vitreous surgery is to remove the qualitatively
      and/or morphologically diseased vitreous. Successful vitrectomy will be
      manifested by an improvement in the structure and/or function of the retina. We
      have evaluated the morphology of the vitreoretinal interface, and the function of
      the retina before and after vitreous surgery. Plasmin-assisted vitrectomy was
      used in some cases to remove the diseased vitreous more efficiently and less
      invasively. The effect of this procedure was assessed by examining the morphology
      and function of the retina. First, the relationship between the qualitative and
      structural abnormality of the vitreous in macular diseases was studied. In
      aphakic/pseudophakic eyes with cystoid macular edema, there was a depression of
      retinal function over the entire retina which may have been caused by chemical
      mediators released into the vitreous. These mediators may have been produced by
      inflammation in the anterior segment of the eye. In eyes with an idiopathic
      macular hole, optical coherence tomographic (OCT) images suggested that the
      progression of the macular hole might depend on a balance between foveal adhesion
      and the posterior vitreous. Second, the efficacy, surgical damage, and
      limitations of vitreous surgery were investigated. The recovery of macular
      function was assessed by focal macular electroretinograms (FMERGs) after
      vitrectomy for epiretinal membrane, choroidal neovascularization, and diabetic
      macular edema. The concurrent examination by optical coherence tomography (OCT)
      suggested that a decrease in retinal thickness contributed to the functional
      recovery. Macular functional recovery was delayed and limited after macular
      translocation, diabetic macular edema, and internal limiting membrane peeling.
      Third, we studied the effect of plasmin-assisted vitrectomy on the retina. The
      plasmin was used to remove the vitreous more completely and less invasively. In
      rabbits, ERG, OCT, and histological examinations demonstrated that the use of
      commercially-available plasmin at a concentration used on human patients resulted
      in temporary adverse effects on the retina. For human patients, we purified the
      plasmin from the patients' serum at the Nagoya University Hospital and the
      activity was about the same as in previous reports. The purified plasmin was
      approved by our hospital's institutional review board, and written informed
      consent was obtained from each patient. Patients with macular edema, idiopathic
      macular hole, and epiretinal membrane without posterior detachment underwent
      plasmin-assisted vitrectomy and were evaluated morphologically and
      electrophysiologically. The efficacy of the plasmin in separating the vitreo
      retinal interface was demonstrated by an occasional spontaneous posterior
      vitreous detachment with or without core vitrectomy, and the presence of less
      vitreous cortex attached to the internal limiting membrane that was removed
      during vitrectomy. This was the first histological demonstration of the
      effectiveness of plasmin in the living eye. Full-field ERGs before and after
      surgery demonstrated clear evidence that no alteration of retinal functional had
      occurred, although we did detect a possible osmotic effect by an increase in OCT
      determined retinal thickness by the high-molecular weight autologous plasmin. In
      future studies, the proper concentration and reaction time for each condition of
      the vitreous should be determined. In conclusion, the pathophysiology of the
      vitreous should reflect the retinal function. The recovery of the structure of
      the retina is important for the recovery of retinal function. This should always
      be the primary goal of surgeons who perform quality surgery.

PMID- 14733134
TI  - [Cell biology of hyalocytes].
AB  - There is a group of cells, called hyalocytes, in the cortical vitreous. Although
      hyalocytes were discovered more than a hundred years ago, the molecular and
      cellular biological characteristics of hyalocytes have yet to be elucidated. In
      this study, we investigated various aspects of hyalocytes and, also performed
      triamcinolone acetonide (TA)-assisted vitrectomy to remove the hyalocytes for
      diabetic macular edema. Immunohistochemical analysis of rat eyes showed that 90%
      of hyalocytes were negative for ED1 but positive for ED2, indicating that
      hyalocyte is a tissue macrophage. Chimeric mice were created by transplanting
      bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated
      wild-type mice, showing the origin of hyalocyte to be bone marrow cells. Bovine
      hyalocytes were cultured successfully. The proliferation of hyalocytes was
      significantly enhanced by hepatocyte growth factor (HGF), platelet-derived growth
      factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth
      factor (FGF-2) and inhibited by transforming growth factor(TGF)-beta. Among
      these, PDGF-BB stimulated the proliferation most potently through the MEK 1
      pathway. Hyalocyte migration assessed by double chamber assay was also stimulated
      by PDGF-BB and it was mediated by the PI3K and p38 MAPK pathways. Cellular
      contraction of hyalocyte was significantly enhanced by PDGF-BB and TGF-beta
      through Rho kinase, p44/42 MAPK, and protein kinase C pathways, as measured by
      collagen gel contraction assay. Next, the relationship between the vitreous
      cavity(VC) and the immune system was studied after intravitreous inoculation with
      ovalbumin (OVA). Injection of OVA into the VC of C 57 BL/6 mice resulted in
      suppressed systemic cell-mediated immunity to OVA as determined by the ear
      swelling assay. This aberrant immune responsiveness following VC injection of OVA
      was termed VC-associated immune deviation or VCAID. The phenomenon of VCAID was
      mediated by intravitreous antigen-presenting cells. The histological study of
      chimeric mice showed these cells to be intravitreous residential cells, namely
      hyalocytes. VCAID was abolished by intravitreous inflammation such as
      experimental autoimmune uveitis. Finally, TA-assisted vitrectomy for diabetic
      macular edema was performed to remove cortical vitreous, because it contained
      many hyalocytes which could secrete inflammatory cytokines including VEGF.
      Although the number of treated eyes was limited, the surgical results have been
      favorable so far. The investigation of hyalocytes would open a new avenue for
      better understanding and development of treatment for various vitreo-retinal
      diseases.

PMID- 14733136
TI  - [Production of tyramine in "moromi" mash during soy sauce fermentation].
AB  - The concentrations of 7 non-volatile amines, tyramine (Tym), histamine (Him),
      phenethylamine (Phm), putrescine (Put), cadaverine (Cad), spermidine (Spd) and
      spermine (Spm) in the liquid part of "moromi" mash during soy sauce fermentation
      were studied. These amines, except for him and Cad, were detected during
      fermentation by the conventional production method in the laboratory. Put and Spd
      were detected at the beginning, and Tym, Phm and Spm appeared later; these 5
      amines increased gradually during the fermentation. Put, Spd, Spm and Cad were
      present in the raw starting material for soy sauce; thus, Tym and Phm were
      produced by the fermentation. When "moromi" mash was added to liquid medium and
      cultivated, Tym was detected in some "moromi" mash and the other amines were not
      detected. Tym-producing bacterial strains were isolated from the liquid culture
      media of Tym-positive "moromi" mash. The Tym-producing strain was a gram-positive
      coccus. The conditions for production of amines by Tym-producing bacterial
      strains were examined. These strains grew and produced tyramine under various
      conditions, which may occur during soy sauce fermentation. Namely, Tym was
      produced at pH 5-10, at salt concentrations of less than 8%, under either aerobic
      or anaerobic conditions. During soy sauce fermentation, it is assumed that Tym
      would be produced by these strains during the early stages of soy sauce aging
      within a short period when the salt concentration and pH conditions are optimal
      for growth. Based on the bacteriological properties, the strains were identified
      as Enterococcus faecium. With the exception of Phm and Him, which did not exist
      in the starting raw material, non-volatile amines (including Put, Cad, Spd and
      Spm) were not produced and microorganisms producing them are not believed to be
      present during "moromi" fermentation.

PMID- 14733135
TI  - [Inter-laboratory evaluation studies of notified ELISA methods for allergic
      substances (egg)].
AB  - Inter-laboratory evaluation studies were conducted for the notified ELISA methods
      for allergic substances (Egg). Standard extracts of egg spiked in extracts of
      sausage, sauce, cookie, bread and cereal at a level of 5-20 ng/mL as the sample
      solution were analyzed in replicate in 10 laboratories. Coefficients of variation
      (CVs) of all three ELISA methods using an Egg Protein ovalbumin ELISA Kit
      (ovalbumin kit), an Egg Protein ovomucoid ELISA Kit (ovomucoid kit) and a FASTKIT
      Egg ELISA kit (Egg ELISA kit) were mostly less than 10%. Mean recoveries of the
      standard extract of egg were over 40% in the three ELISA methods. Repeatability
      relative standard deviations of egg standard solution in five food extracts were
      in the ranges of 18.7-25.5%, 18.6-41.8%, 21.3-43.3% for the ovalbumin kit, the
      ovomucoid kit and the Egg ELISA kit, respectively. Reproducibility relative
      standard deviations of egg standard solution in five food extracts were 16.8
      35.1%, 19.6-35.8%, 24.7-51.1% for the ovalbumin kit, the ovomucoid kit and the
      Egg ELISA kit, respectively. The detection limits of all the ELISA methods were 4
      5 ng/mL in sample solutions. These results suggested that the notified ELISA
      methods are reliable and reproducible for the inspection of egg protein levels in
      extracts of sausage, sauce, cookie, bread and cereal.

PMID- 14733137
TI  - [Examination of sex-hormonal activity of some additives for PVDC film].
AB  - Stabilizers (epoxidized linseed oil and epoxidized soybean oil) and plasticizers
      (acetyl tributyl citrate, diacetyl monolauryl glyceride and dibutyl sebacate)
      commonly used in polyvinylidene chloride (PVDC) films and extracts of such films
      were investigated for estrogenic and androgenic activity by means of estrogen
      receptor (ER) and androgen receptor (AR) competitive ligand-binding assays.
      Further, in in vivo experiments, ovariectomized Sprague-Dawley rats were observed
      for uterine wet weight change, uterine endometrium hyperplasia and vaginal mucosa
      cornification, following administration of each test compound or extract orally
      (0.5 or 500 mg/kg) or subcutaneously (0.5 or 100 mg/kg). No significant response
      or change was observed with any of the test compounds or extracts, either in
      vitro or in vivo. The results thus indicate that neither the stabilizers and
      plasticizers used in PVDC films, nor their extracts, exert sex-hormonal activity.

PMID- 14733138
TI  - [An experimental proficiency test for ability to screen 104 residual pesticides
      in agricultural products].
AB  - An experimental proficiency test program for ability to screen 104 residual
      pesticides in agricultural products has been conducted. Eight Japanese
      laboratories joined the program. Items tested in the present study were limit of
      detection, internal proficiency test (self spike) and external proficiency test
      (blind spike). All 104 pesticides were well detected and recovered from
      agricultural foods in the internal proficiency test. However, the results of the
      external proficiency test did not completely agree with those of the internal
      proficiency tests. After 5 rounds of the blind spike test, the ratio of the
      number of correctly detected pesticides to that of actually contained ones (49
      total) ranged from 65% to 100% among laboratories. The numbers of mistakenly
      detected pesticides by a laboratory were 0 to 15. Thus, there was a great
      difference among the laboratories in the ability to screen multiresidual
      pesticides.

PMID- 14733139
TI  - [Determination of benzimidazole anthelmintics in livestock foods by HPLC].
AB  - A simple and rapid liquid chromatographic method was developed for the
      simultaneous determination of twelve benzimidazole anthelmintics in livestock
      foods using reversed-phase high-performance liquid chromatography with photodiode
      array detection (PDA). A sample was homogenized with acetonitrile and n-hexane,
      and centrifuged. The acetonitrile phase was isolated and evaporated. The residue
      was dissolved in 0.1 mol/L carbonate buffer solution (pH = 9.1), sonicated, and
      then subjected to clean-up on a Bond Elut LRC-C18 cartridge. The benzimidazole
      compounds were separated isocratically on a Capcell Pak C18 UG 120 (5 microns,
      150 x 4.6 mm i.d.) column and detected by PDA at 295 and 313 nm. Mixtures of
      acetonitrile and 0.05 mol/L ammonium acetate in mixing ratios of (20:80) and
      (40:60) were used as the mobile phase, and the flow-rate was 1.0 mL/min at 40
      degrees C. The mean recoveries (n = 3) from 0.1-0.5 microgram/g added samples
      were 72.6-97.2% with coefficients of variation of 0.3-8.5%. The detection limits
      were 0.01-0.05 microgram/g.

PMID- 14733140
TI  - [Simultaneous determination of pesticide residues in fruits and vegetables by
      GC/MS (SCAN mode) and HPLC].
AB  - A method was developed for simultaneous determination of pesticide residues in
      fruits and vegetables. Residues were extracted from samples with acetonitrile,
      followed by a salting-out step and a partitioning step with n-hexane at the same
      time. Co-extractives were removed with ENVI-Carb/LC-NH2 mini-column cleanup.
      Analysis was performed by GC/MS (SCAN mode) and HPLC. Of the 139 pesticides
      spiked at 0.1 or 0.5 microgram/g into 6 fruits and vegetables (spinach, tomato,
      apple, radish, cabbage and carrot), recoveries of 117 pesticides were between 70
      and 120%. This method is appropriate for determining these pesticides and for
      screening several other pesticides for which the recoveries were < or = 70% or >
      or = 120% (imazalil, etc.). The limits of detection for most pesticides in this
      method were equal to or lower than those of the bulletin method in Japan.

PMID- 14733141
TI  - [Simultaneous determination of N-methylcarbamate and urea pesticides in
      agricultural products by LC/MS].
AB  - A simultaneous determination method of 7 N-methylcarbamate and 7 urea pesticides
      in agricultural products by liquid chromatography/mass spectrometry (LC/MS) has
      been developed. Under reversed-phase liquid chromatographic conditions, 14
      pesticides were analyzed using electrospray ionization (ESI) with simultaneous
      acquisition of positive ions and negative ions. Fourteen pesticides were
      extracted with acetone, 10% NaCl solution was added, and the pesticides were re
      extracted with dichloromethane. The extract was concentrated under reduced
      pressure, and dissolved in methanol. The detection limits of 14 pesticides ranged
      from 0.0012 to 0.0056 microgram/g. The recoveries of pesticides were from 36.5 to
      112.5% [RSD (n = 3) ranged from 0.5 to 48.1%] for 4 agricultural products.

PMID- 14733142
TI  - Dispersion and solubilization of carbon nanotubes.
AB  - Carbon nanotubes are generally insoluble in any solvents, resulting in their poor
      processability for many proposed potential applications. Several strategies have
      been developed to introduce carbon nanotubes into solvent systems, including
      dispersion and suspension under special experimental conditions and the chemical
      modification and functionalization. The well-dispersed and solubilized carbon
      nanotubes make it possible to characterize and study the carbon nanotubes by
      using solution-based techniques, to realize some of the unique properties of the
      nanotubes, and to carry out further chemical transformations. In this review,
      recent development in the experimental methods for the dispersion and
      solubilization of carbon nanotubes will be summarized and discussed.

PMID- 14733143
TI  - Monodispersed quinacridone nanocrystals prepared by a high-temperature and high
      pressure liquid crystallization method.
AB  - Monodispersed quinacridone nanocrystals were fabricated by a high-temperature and
      high-pressure liquid crystallization method, which proved to be an advanced
      technique for fabricating nanocrystals of pigment compound. The aqueous
      dispersion liquid of quinacridone nanocrystals was very stable. The nanocrystats
      had a spherical shape with an average size of 60 nm when water was used as the
      high-temperature and high-pressure liquid at 260 degrees C and cooling solvent.
      The crystal structure of the nanocrystals could be controlled by varying the
      experimental conditions.

PMID- 14733144
TI  - Role of self-assembled gold nanodots in improving the electrical and optical
      characteristics of zinc oxide films.
AB  - We have studied the effect of embedding nanocrystalline Au particles on the
      electrical and optical characteristics of ZnO films. Au-embedded epitaxial ZnO
      films were deposited on (0001) sapphire substrates with a pulsed laser deposition
      technique. The crystalline quality of both the ZnO matrix and Au nanoparticles
      was investigated by X-ray diffraction and transmission electron microscopy.
      Composite films were characterized by photoluminescence, optical absorption, and
      low-temperature electrical resistivity measurements. Photoluminescence spectra of
      theses films showed a sharp excitonic peak at 3.22 +/- 0.05 eV without any
      signature of green band emission. Electrical resistivity measurements showed
      these films to be highly conducting, with a room-temperature resistivity of 3.4
      +/- 0.2 m omega-cm.

PMID- 14733145
TI  - A new method for the synthesis of hydrophobic gold nanotapes.
AB  - Protocols for the synthesis of gold nanoparticles are increasingly focusing on
      controlling the morphology of the nanocrystals. We demonstrate in this article
      the facile, one-step synthesis of gold nanotapes that are readily dispersible in
      organic media. This is accomplished by the spontaneous reduction of aqueous
      chloroaurate ions by hexadecylaniline molecules present in chloroform at the
      static interface between water and chloroform. The hexadecylaniline molecules cap
      the gold nanotapes thus formed, rendering them hydrophobic and dispersible in a
      range on nonpolar and weakly polar organic solvents. Possible reasons for the
      growth of gold nanotapes are discussed.

PMID- 14733146
TI  - Nanoporous aluminum oxide as a novel support material for enzyme biosensors.
AB  - To construct novel amperometric sensors for the detection of hydrogen peroxide
      and pyruvate, peroxidase and pyruvate oxidase were immobilized in self-supporting
      nanoporous alumina membranes those made by anodic oxidation. Pyruvate oxidase and
      other enzymes were enclosed in poly(carbamoylsulfonate) hydrogel and sucked into
      the nanoporous alumina structure before polymerization. The alumina membranes
      were investigated by scanning electron microscopy before and after the enzyme
      immobilization. In an amperometric flow detector cell, pyruvate and hydrogen
      peroxide were detected under flow injection analysis conditions in concentration
      ranges from 1 microM to 100 microM and 5 microM to 500 microM, respectively. The
      achieved operational stability showed that alumina membranes can be used to
      construct enzyme-modified electrodes.

PMID- 14733147
TI  - Visualizing the self-assembly of tubulin with luminescent nanorods.
AB  - We succeeded in labeling tubulin with luminescent CdSe nanorods. The labeled
      tubulin was still able to self-assemble into microtubules, demonstrating that the
      protein has remained functional. The comparison with rhodamine-labeled tubulin
      revealed that whereas the rhodamine bleached completely within the observed time
      frame, the nanorods did not show any bleaching, which makes it possible to follow
      the key events of self-assembly at high time resolution. Preparation and
      derivatization of nanorods are described. Water-soluble, protein-reactive group
      containing particles were covalently coupled to tubulin. The conjugate was
      purified by one cycle of assembly and disassembly and used to induce the
      formation of fluorescent microtubules. These results suggest that the use of
      luminescent nanorods should allow continuous confocal monitoring of dynamic
      biological processes.

PMID- 14733148
TI  - Template synthesis of nanophase mesocarbon.
AB  - Templating techniques are used increasingly to create carbon materials with
      precisely engineered pore systems. This article presents a new templating
      technique that achieves simultaneous control of pore structure and molecular
      (crystal) structure in a single synthesis step. With the use of discotic liquid
      crystalline precursors, unique carbon structures can be engineered by selecting
      the size and geometry of the confining spaces and selecting the template material
      to induce edge-on or face-on orientation of the discotic precursor. Here
      mesophase pitch is infiltrated by capillary forces into a nanoporous glass
      followed by slow carbonization and NaOH etching. The resulting porous carbon
      material exhibits interconnected solid grains about 100 nm in size, a
      monodisperse pore size of 60 nm, 42% total porosity, and an abundance of edge
      plane inner surfaces that reflect the favored edge-on anchoring of the mesophase
      precursor on glass. This new carbon form is potentially interesting for a number
      of important applications in which uniform large pores, active-site-rich
      surfaces, and easy access to interlayer spaces in nanometric grains are
      advantageous.

PMID- 14733149
TI  - Optical and magnetic properties of manganese-doped zinc sulfide nanoclusters.
AB  - We report the synthesis of fixed-size ZnS nanoclusters approximately 24 A in
      diameter with varying manganese concentrations. Various samples of Zn1-x MnxS,
      with x = 0, 0.02, 0.055, 0.09, and 0.13, have been prepared and characterized
      using X-ray diffraction, energy-dispersive analysis of X-rays, UV absorption,
      fluorescence emission and excitation, electron paramagnetic resonance (EPR), and
      magnetic susceptibility measurements. The manganese ions are found to substitute
      Zn randomly without giving rise to any clustering of Mn sites, as seen from EPR
      and magnetic susceptibility results. Our studies reveal that the band gap of the
      doped nanoclusters passes through a maximum as the manganese concentration is
      varied. Also, we observe orange emission from Mn2+ ions in the doped ZnS
      nanoclusters, apart from the blue emission characteristic of the ZnS defect
      states. The relative intensity of the orange emission compared with the blue
      varies with the manganese concentration in a nonmonotonic way. The inverse of
      susceptibility temperature plots can be plotted onto a universal curve by simple
      multiplicative constants, thus showing that the magnetic interactions between
      Mn2+ ions are weak.

PMID- 14733151
TI  - Growth and characterization of tetragonal Mn3O4 nanowires.
AB  - Mn3O4 nanowires were synthesized by calcination of a precursor obtained in a
      novel microemulsion. Transmission electron microscopy, X-ray diffraction,
      infrared spectroscopy, X-ray photoelectron spectroscopy, and selected area
      electron diffraction were used to characterize the structural features and
      chemical compositions of the as-synthesized nanowires. The results showed that
      the as prepared nanowires are composed of tetragonal Mn3O4, the diameters range
      from 50 to 800 nm, and lengths reach tens of micrometers. The nanowires are
      highly promising for applications in magnetic materials and sensors.

PMID- 14733150
TI  - Electrocatalytic reduction of chloramphenicol at multiwall carbon nanotube
      modified electrodes.
AB  - A multiwall carbon nanotube-modified glassy carbon (GC) electrode was employed
      for the investigation of chloramphenicol (CAP) reduction. Carbon nanotube coating
      can greatly lower the overpotential of the electrochemical reduction of CAP and
      promote the electrode reaction. CAP undergoes an irreversible reduction process
      in phosphate buffer by the modified electrode. The reduction peak current (Ip)
      was significantly increased. Effects of some important factors, including pH,
      scan rate, and amount of modifier, on the determination of CAP were investigated.
      In the range of 3 x 10(-7) to 1.2 x 10(-5) M, the reduction peak current (Ip) has
      a good linear relationship with the concentration of CAP. When the signal-to
      noise ratio is 3, the detection limit is 4.5 x 10(-8) M. The relative standard
      deviation of 10 measurements for 3 x 10(-6) M CAP is 5.3%, suggesting an
      excellent reproducibility of the modified electrode. Interfering experiments show
      that the modified electrode has excellent selectivity for the detection of CAP.
      The modified electrode was used to determine CAP in eyedrops, and the recoveries
      were approximately 100%.

PMID- 14733152
TI  - Interaction mechanism of in-situ nano-TiN-AlN particles and solid/liquid
      interface during solidification.
AB  - This paper deals with the interaction mechanism between in situ nanometer-grade
      TiN-AlN particles and the solid/liquid (S/L) interface during the solidification
      of an in situ TiN-AlN/Al composite. According to the setting of a force balance
      for the particles in front of the S/L interface during solidification, F =
      F(buoyant) + F(repulsive) + F(viscous). We obtained the relationship between the
      critical cooling velocity of the liquid composite, Vr, and the size of the
      ceramic particle, rp. By this relationship formula, we can know that the S/L
      interface engulfs particles or pushes them to the crystal grain boundary during
      the solidification of a TiN-AlN/Al composite. It is found that Vr is proportional
      to the radius of ceramic particles by transmission electron microscope (TEM)
      observation. The TEM test indicates that the smaller the particle is, the more
      easily the S/L interface engulfs particles.

PMID- 14733153
TI  - Morphology and microstructure at different scales of porous silicon prepared by a
      nonconventional technique.
AB  - In this work we present first results concerning the detailed structure of porous
      silicon (PS) layers prepared by a new method using a vapour-etching (VE)-based
      technique. Studies of the photoluminescence properties of VE-based PS show that
      the visible emission occurs at high energies as compared with PS prepared by
      conventional techniques. To understand the VE-based PS features, we need to point
      out the PS microstructure throughout its general morphology. For this purpose a
      microscopy multiscale study was done. Scanning, conventional transmission, and
      high-resolution transmission electron microscopes were employed. The
      investigations were made on PS films prepared from moderately and heavily doped n
      and p-type silicon. SEM images show that VE-based PS layers are essentially
      formed of clusters like interconnected structures. TEM studies show that these
      clusters are composed of nanocrystallites with different shapes. The effect of
      the doping type of the starting Si substrate on the characteristics of the PS
      layers was examined (thickness, porosity, behavior). Pore propagation was found
      to depend on doping type. The crystallinity of the PS layers was also locally
      studied in depth.

PMID- 14733155
TI  - Multiscale modeling of carbon nanotube reinforced polymer composites.
AB  - This article examines the effect of interfacial load transfer on the stress
      distribution in carbon nanotube/polymer composites through a stress analysis of
      the nanotube/matrix system. Both isostrain and isostress loading conditions are
      investigated. The nanotube is modeled by the molecular structural mechanics
      method at the atomistic level. The matrix is modeled by the finite element
      method, and the nanotube/matrix interface is assumed to be bonded either
      perfectly or by van der Waals interactions. The fundamental issues examined
      include the interfacial shear stress distribution, stress concentration in the
      matrix in the vicinity of nanotube ends, axial stress profile in the nanotube,
      and the effect of nanotube aspect ratio on load transfer.

PMID- 14733154
TI  - Raman scattering investigations of nanocrystalline thorium oxide.
AB  - Raman scattering investigations are carried out on nanocrystalline thorium oxide
      powders. Shift and broadening of the Raman peak associated with F2g phonons are
      observed for the nanocrystalline samples as compared with those of the bulk. The
      peak shift and broadening are found to increase further as the particle size
      decreases. A quantitative analysis of the Raman line shape is carried out with a
      Gaussian confinement model, and the estimated size is found to be consistent with
      that obtained from X-ray diffraction and transmission electron microscopy.

PMID- 14733156
TI  - The Faculty of Dental Medicine in Jerusalem--50 years of pioneering dentistry.

PMID- 14733157
TI  - New services mean increased production.
AB  - Building a practice by adding new services is an extremely intelligent approach
      to practice expansion. The key is to select services that are profitable,
      manageable, relatively easy to implement, and, most importantly, desirable to
      patients. Dentin hypersensitivity is a good example of a situation requiring
      simple services that are easily implemented. The easiest part of implementing the
      service will be case acceptance. Fortunately, these patients are already
      comfortable with the practice and are very likely to perceive the value of the
      service. Offering new services to existing patients will almost certainly
      increase practice production. Therefore, the only question a dentist must ask is
      which new services will be added to the practice.

PMID- 14733158
TI  - Restoration modalities of severely injured anterior teeth--gingival integration,
      papillae support, and predictable imperfections.
AB  - This article presents 4 cases, each describing a different dental trauma and a
      different treatment modality. Because of various limitations, none of the results
      presented is esthetically perfect, but the outcomes were acceptable to both the
      operators and the patients. Such limitations should be predicted and discussed
      with patients before beginning treatment and should be regarded as acceptable
      compromises, unless other less conservative treatments are to be used.

PMID- 14733159
TI  - Management of chronic orofacial pain: today and tomorrow.
AB  - In the facial region, chronic pain syndromes include musculoskeletal pain,
      neuropathic disorders, vascular pain, and other chronic headaches. Therapy of
      chronic facial pain syndromes often relies on long-term psychotropic medications
      that cause severe side effects and offer nontotal pain relief. In this article,
      therapeutically relevant advances in science, which will change the approach to
      pain management, are reviewed. Understanding the mechanisms involved in chronic
      pain enables the clinician to skillfully apply this knowledge when selecting a
      therapy.

PMID- 14733160
TI  - The use of lasers in dentistry: principles of operation and clinical
      applications.
AB  - This article describes the principles of laser operation and the clinical
      application of laser technology in the different fields of dentistry. It
      discusses the use of the Er:YAG laser in restorative dentistry, pediatric
      dentistry, and periodontics, as well as the introduction of a new side-firing
      spiral tip for efficient cleaning of the root canal system by means of lateral
      laser irradiation. Although the Er:YAG laser is used mostly on enamel and dentin,
      the gingival depigmentation procedure using this laser also is described.
      Clinical applications of the CO2 and diode lasers on soft tissues, particularly
      in the fields of oral and maxillofacial surgery and perodontics, are explained.
      Because teeth whitening for esthetic reasons has gained increasing popularity in
      dentistry, the application of diode lasers for this purpose is discussed. All the
      dental laser procedures described in this article are conducted at the Hebrew
      University-Hadassah School of Dental Medicine and are further investigated in
      various clinical research projects.

PMID- 14733161
TI  - [Phathophysiological response to surgical insults: new findings].

PMID- 14733162
TI  - [Role of internal mediators in surgical stress].
AB  - In surgical stress, internal mediators include cytokines released locally as well
      as into the circulation; activation of neutrophils, monocytes, macrophages,
      endothelial cells, platelets and other cells; activation of plasma protein
      cascade systems such the complement, coagulation, fibrinolytic and contact
      systems the release of tissue-damaging proteinases; the formation of lipid
      mediators such as eicosanoids and platelet-activating factor; and the generation
      of oxygen and nitrogen radicals. In addition, during host defense rections, a
      number of agents are released that blunt the inflammatory response, such as anti
      inflamatory cytokines, soluble cytokine receptors, acute-phase proteins including
      proteinase inhibitors and stress hormones. In this paper, we explain such
      internal mediators.

PMID- 14733163
TI  - [Neuroendocrine response to critical illness and nutritional pharmacology].
AB  - Injury and infection produce significant alterations in metabolic homeostasis.
      Host humoral factors, such as the counterregulatory hormones epinephrine,
      cortisol, and glucagons, play important roles in metabolic changes postinjury.
      Hyperglycemia associated with insulin resistance is common in critically ill
      patients, even those who have an uneventful course postinjury. The use of
      exogenous insulin to maintain blood glucose at a level no higher than 110 mg per
      deciliter, known as intensive insulin therapy, has reduced morbidity and
      mortality among critically ill patients. Glucocorticoids and various
      proinflammatory cytokines are important regulators of muscle proteolysis in
      stressed patients. With regard to nutritional support, enteral feeding is
      superior to parenteral feeding and early feeding is better than late feeding.
      Immune-enhancing diets has been shown in several recent studies to improve
      outcome in critically ill patients. Moreover, various hormones, including
      insulin, growth hormone, and insulin-like growth factor-1, may blunt muscle
      cachexia. Other treatments including cytokine antibodies, induction of heat-shock
      protein, and calcium antagonists, may prevent the catabolic response to stress,
      and these methods are important considering the significant clinical consequences
      of protein catabolism.

PMID- 14733165
TI  - [Pathophysiology and treatment of postoperative acute respiratory disturbance].
AB  - One major concern after surgery is postoperative pulmonary complications such as
      atelectasis, aspiration, pneumonia, and respiratory failure. Progress in
      preoperative and postoperative rehabilitation, in systemic management including
      respiratory management, and progress in understanding the pathophysiology of
      acute respiratory failure have improved prevention and the outcome of treatment.
      However, some conditions remain very difficult to treat, like respiratory failure
      accompanied by infection or multiple organ failure. In the 1960s, the concept of
      acute respiratory distress syndrome or adult respiratory distress syndrome was
      postulated. Tremendous amounts of basic and clinical research have been done to
      clarify the pathophysiology of and to establish treatment modalities for acute
      respiratory failure. Our understanding of acute respiratory failure has
      progressed from the role of microembolism syndrome to cellular components such as
      neutrophils and platelets and then to humoral factors such as endotoxins,
      complement factors, and numerous cytokines. In this article, the pathophysiology
      of acute lung injury and its diagnostic criteria, treatment modalities such as
      respirator management to protect lung tissue from barotrama and volutrauma by
      yielding hypercapnea (permissive hypercapnea), drug therapy with neutrophil
      elastase inhibitor, mechanical support using extracorporeal membrane oxygenation,
      liquid ventilation, continuous hemodiafiltration, and endotoxin elimination
      columns are discussed. Early diagnosis and early treatment are mandatory to
      improve survival in patients with acute respiratory failure, although we have not
      yet fully understood the pathophysiology of this disease entity sufficiently.

PMID- 14733164
TI  - [Mechanism of immune suppression after surgical stress and host defense against
      infection].
AB  - Suppression of cellular immunity secondary to decreased immunocyte function is
      one of the surgical stress-induced biological responses. Monocytes/macrophages,
      natural killer (NK) cells, lymphocytes, and neutrophils play an important role in
      this immune system. These immunity charge cells are expressed through various
      surface antigens, such as major histocompatibility complex (MHC) class antigens,
      T cell receptors, and the cytokines interferon-gamma, interleukin (IL)-2, and IL
      12. MHC class II antigen expression of monocytes and the cytokine production of
      CD4+ T cells are decreased after surgical stress. In this immune-suppressed
      condition, patients after surgical stress can easily experience infectious
      complications, and therefore the up-regulation of the immune system is necessary
      to avoid those complications. Recently, the role of natural immunity as a defense
      system against infection has received attention. The discovery of Toll-like
      receptor families revealed how the macrophage system cells recognize
      microorganisms. Furthermore, liver natural killer(NK) cells and NK T cells are
      important to induce the Th1 immune response in bacterial peritonitis. In this
      manuscript, we explain the mechanism of immune suppression after surgical stress
      and the host defense against infection by analyzing cytokine production and
      surface membrane molecules in mononuclear cells.

PMID- 14733166
TI  - [Pathophysiologies of ischemic/reperfusion injuries associating with hemorrhagic
      shock and up-to-date treatment].
AB  - During the ischemic state, hypoxanthine and xanthine oxidase are accumulated in
      the ischemic cells, and thereafter when oxygen is reperfused into ischemic cells,
      hypoxanthine and xanthine oxidase work to change oxygen into oxygen radicals.
      Oxygen radicals themselves damage various cells and they also injure cells by
      activating the transcription factors of inflammatory cells to induce special
      protein synthesis depending on individual cells. These processes are considered
      to be related to the systemic inflammatory response syndrome (SIRS) and multiple
      organ dysfunction syndrome (MODS). Hemorrhagic shock is a generalized ischemic
      state and intestinal ischemia is more profound and more severely damaging than in
      other vital organs because of luxurious flow to the latter organs. The lack of
      microcirculation in large areas of the intestinal mucosa and in high-density
      areas of intestinal immune cells results in the synthesis of various inflammatory
      mediators, in the appearance of adhesion molecules, in the induction of tissue
      factors, and finally in the development of impairment of remote vital organs and
      MODS when oxygen is reperfused. There is no therapy for reperfusion injury after
      a prolonged ischemic state, and thus it is most important to reduce the
      intestinal ischemic time by supplying sufficient oxygen to preserve intestinal
      circulation and to commence early enteral nutrition. The development of new
      treatments to interrupt the vicious pathological cascade inducing MODS after
      ischemic reperfusion injury is mandatory.

PMID- 14733167
TI  - [Coagulofibrinolytic response to surgical insult].
AB  - During recent years, evidence has accumulated demonstrating bidirectional cross
      talk in the classic neuroendocrine response as well as immune-mediated
      inflammatory response, and newly described coagulofibrinolytic response. This
      review outlines the influences that these systems exert on each other and
      discusses the implications of the coagulofibrinolytic response to the multiple
      organ dysfunction syndrome (MODS) and patient prognosis. The results of the
      physiological coagulofibrinolytic response to physical insults such as surgery
      and trauma are hemostasis and wound healing. We stress that this response is
      nonspecific and is similar in all types of insult without exception. An abnormal
      hemostatic response to surgical insult is called disseminated intravascular
      coagulation (DIC). DIC associated with the sustained systemic inflammatory
      response syndrome (SIRS) in postsurgical insult leads to the development of MODS,
      which is the main determinant of patient outcome. To prevent the progression of
      DIC, new drugs like activated protein C which can control both coagulation and
      inflammation now appear promising.

PMID- 14733168
TI  - [Control of the biological response to planned and unplanned injuries].
AB  - The biological response to planned and unplanned injuries is discussed in terms
      of the time course and both local and systemic states. In the systemic and local
      inflammatory response syndrome, the excess systemic cytokine reaction must be
      controlled. However, in the local inflammation-induced systemic immunosuppression
      syndrome, the fundamental defensive response should be maintained or even
      reinforced. Uniform measures for cytokine reaction are inadequate.

PMID- 14733169
TI  - [What we can learn from a case of medical malpractice].

PMID- 14733170
TI  - [Current status and prospect of T cell costimulatory blockade in
      transplantation].
AB  - Organ transplantation has been widely accepted as a routine medical treatment in
      Japan. The recent introduction of new immunosuppressive reagents may improve
      outcome after transplantation. However, further investigations are required to
      achieve the prevention of chronic rejection and the induction of donor-specific
      tolerance in clinical transplantation. The potential of costimulatory blockade in
      controlling allograft rejection is now extensively under investigation. Although
      costimulatory blockade can prevent rejection and induce tolerance experimentally,
      there are several issues that need to be clarified before its clinical
      application. Recently, several novel costimulatory pathways have also been
      reported. Each costimulatory pathway has distinct and unique immunological roles
      in T cell activation and down-regulation. Upon the perception of underlying
      mechanisms, the theoretical and effective use of costimulatory blockade in
      combination with conventional immunosuppression and/or novel molecular targeting
      therapies might make a major breakthrough in clinical transplantation.

PMID- 14733171
TI  - The casualization and fragmentation of nursing care and the impact on patients
      and nurses.

PMID- 14733172
TI  - Professional nursing organizations: what nurses want.

PMID- 14733173
TI  - The Codman Award Paper: quality of life in stroke survivors and their spouses:
      predictors and clinical implications for rehabilitation teams.
AB  - Valuing and promoting quality of life after stroke is an essential component of
      practice for neuroscience nurses and other clinicians working in rehabilitation
      settings. Although some research studies have addressed factors that contribute
      to quality of life post-stroke, the majority of studies have focused on stroke
      survivors, not their spouses. Additionally, little attention has been given to
      family strengths associated with quality of life. In this paper, the investigator
      presents the findings of a recent descriptive, correlational study that was based
      on the conceptual framework of the Developmental Model of Health and Nursing
      (DMHN) (Allen & Warner, 2002; Ford-Gilboe, 2002a). This was the first study to
      examine the relationships among hope, family health promoting activity, and
      quality of life. The study was conducted with a convenience sample of 40 stroke
      survivors with moderate to severe functional impairments and their spouses.
      Participants had completed a rehabilitation program. Spouses' employment status,
      number of supports, and functional independence at discharge were common
      predictors of quality of life for both partners. However, hope was found to
      contribute to quality of life of stroke survivors, but not their spouses. The
      different patterns of findings are discussed and the key implications for
      clinical and research practice are addressed.

PMID- 14733174
TI  - Do we need stimulation programs as a part of nursing care for patients in
      "persistent vegetative state"? A conceptual analysis.
AB  - The rehabilitative care of persons suffering long-lasting effects of brain injury
      is a significant challenge for nurses as they are the health professionals who
      usually spend the most time with them. Historically in Germany, the term "apallic
      syndrome" has been commonly used for what Plum and Posner (1980) termed the
      persistent vegetative state. When persons are diagnosed as being in a persistent
      vegetative state, that is awake but not aware, for more than six months, they
      seldom receive active therapy except what nurses or families may provide.
      Stimulation programs have been advocated for these persons, but there is still no
      reliable evidence as to their effectiveness, and the conceptual basis of the two
      main types of programs has been poorly understood. The multisensory stimulation
      approach, such as the Coma Recovery Program or Coma Arousal Therapy, is based on
      behaviourism with the belief that intensive stimulation provided to all senses
      will enhance synaptic reinnervation and stimulate the reticular activating system
      to increase brain tone. In contrast, the sensory regulation approach is based on
      information processing and mediation of reaction to sensory information with
      emphasis on enhancing selective attention by regulating the environment rather
      than providing high degrees of stimulation. What both approaches have in common
      is the belief that the person in a persistent vegetative state may, at some
      level, be able to perceive and begin to process information and that external
      stimulation may enhance that process. Nurses interacting with persons in
      persistent vegetative state are encouraged to think about how they can regulate
      sensory input to enhance meaning and facilitate information processing for these
      persons.

PMID- 14733175
TI  - Data sharing on the horizon.

PMID- 14733176
TI  - Quality care tops OIG work plan.

PMID- 14733177
TI  - Osteoporosis: silent no more.

PMID- 14733178
TI  - Calculating a fair business price.

PMID- 14733179
TI  - Staffing effort is education-driven.

PMID- 14733180
TI  - [Prospects of the application of seed-coating techniques to medicinal plants].

PMID- 14733181
TI  - [Prosthesis implantation in current hand surgery].

PMID- 14733182
TI  - [Pain and occupational disability].

PMID- 14733183
TI  - [Thoughts on the planned inclusion of selected knee and hip arthroses on the list
      of occupational diseases].

PMID- 14733184
TI  - Role of NF-kappaB in inflammatory disorders: just when you thought you knew
      everything!

PMID- 14733185
TI  - Iranian government draws up plans to rebuild Bam. Restoration of health-care
      facilities is a priority for the Iranian government and international aid
      agencies.

PMID- 14733186
TI  - Growth hormone for short bowel adaptation: is less more effective than more?

PMID- 14733187
TI  - Preventing pregnancy malaria. Simple vaccines that stop parasites lodging in the
      placenta may save thousands of lives.

PMID- 14733188
TI  - China culls wild animals to prevent new SARS threat.

PMID- 14733189
TI  - [A child with a full stomach has to be anaesthesized...Anasthesiol Intensivmed
      Notfallmed Schmerzther; 37; 514-519].

PMID- 14733190
TI  - Cracking the risk of fractures in Crohn disease.

PMID- 14733191
TI  - [A child with a full stomach has to be anaesthesized...Anasthesiol Intensivmed
      Notfallmed Schmerzther; 37; 514-519. Reply].

PMID- 14733192
TI  - Flu jab shortage in Japan puts elderly at risk.

PMID- 14733193
TI  - FDA issues alert on ephedra supplements in the USA.

PMID- 14733194
TI  - India bans tobacco advertising and smoking in public places.

PMID- 14733195
TI  - EC grant helps counter Chechen refugee-camp closures.

PMID- 14733196
TI  - Space agency donates satellites to help study Ebola.

PMID- 14733197
TI  - Italian health bill to overhaul management of NHS hospitals. Bill will phase out
      monocratic "supermanagers" and give greater powers to hospital doctors.

PMID- 14733198
TI  - Imprinted chromosomal regions of the human genome have unusually high
      recombination rates.

PMID- 14733200
TI  - Bibliography. Current world literature.

PMID- 14733199
TI  - [BMGS presents corner points for further development of nursing insurance].

PMID- 14733201
TI  - Bibliography. Current world literature. Vasculitis syndromes.

PMID- 14733202
TI  - Bibliography. Current world literature. Systemic disorders with rheumatic
      manifestations.

PMID- 14733203
TI  - [SARS reflection: a framework for improving public health systems in China].

PMID- 14733204
TI  - [Monitoring curarization in anesthesia and resuscitation].

PMID- 14733205
TI  - [Are IVF results predictable through the analysis of sperm DNA fragmentation?].

PMID- 14733206
TI  - Making medical decisions for a seriously sick child: some ethical dilemmas.

PMID- 14733207
TI  - Jodie and Mary.

PMID- 14733208
TI  - Disruptive visions: biosurgery.
AB  - There are a number of new therapeutic options generated by the biotechnology,
      bioengineering, and bioimaging revolutions in terms of organ-specific designer
      drugs, genetically engineered cells, cell-specific proteins and drugs, directed
      energy instruments, therapeutic microdevices, etc. Many of these new therapies
      need to be placed exactly on, within, or adjacent to an organ, and many others
      are delivered by endoluminal or endovascular approaches. The common requirements
      are (1) the accurate delivery of the modality and (2) the functional importance
      of targeting the biologic basis rather than the anatomic structure--hence the
      term biosurgery. As more of these therapies achieve clinical applicability and
      FDA approval, there will be the need for the precision of delivery to be at the
      micro- and nanoscale, which is well beyond human physical limitations. The
      surgeon of the future must be able to identify those therapeutic modalities that
      would benefit from such exact placement or implantation and acquire the skills,
      training, and equipment to use surgical expertise to deliver these new
      modalities. A review of some of the emerging opportunities is presented. Ignoring
      these challenges will relinquish these new procedures to other nonsurgical
      interventionalists, perhaps to the detriment of patient safety.

PMID- 14733209
TI  - Recommended childhood and adolescent immunization schedule--United States,
      January-June 2004.

PMID- 14733210
TI  - Can we make the leap from the lab to the operating room?

PMID- 14733211
TI  - Ethical guidelines to publication of chemical research.

PMID- 14733212
TI  - Ask us. A fairly severe mouth breathing habit.

PMID- 14733213
TI  - Searching PubMed for evidence-based dentistry.

PMID- 14733214
TI  - Does "evidence-based research" provide needed evidence?

PMID- 14733215
TI  - Provocative thoughts about tomorrow's orthodontists today.

PMID- 14733216
TI  - Functional appliance treatment.

PMID- 14733217
TI  - Re: The accuracy of stereolithography in planning craniofacial bone replacement.

PMID- 14733223
TI  - Misconceptions about condom efficacy linked to high risk of unprotected sex among
      Chinese STD patients.

PMID- 14733218
TI  - [Language problems].

PMID- 14733224
TI  - Health of children in rural India may reflect whether parents have met their
      goals for family composition.

PMID- 14733225
TI  - Women who know a person with AIDS do not have elevated condom use rates.

PMID- 14733226
TI  - In Zimbabwe, substantial minorities of women are accepting of wife-beating.

PMID- 14733227
TI  - In Asia, child mortality is not linked to women's autonomy or religion.

PMID- 14733228
TI  - In South Africa, having one pap smear lowers women's chances of cervical cancer.

PMID- 14733229
TI  - Proceedings of the 16th Annual National Cooperative Growth Study (NCGS) and the
      3rd Annual National Cooperative Somatropin Surveillance (NCSS) Investigator
      Meeting. Chicago, Illinois, USA. October 17-20, 2002.

PMID- 14733230
TI  - Improving early diagnosis of oral cancer.

PMID- 14733231
TI  - Closed reduction, an effective alternative for comminuted.

PMID- 14733232
TI  - Comments on the pathogenesis and medical treatment of central giant cell
      granulomas.

PMID- 14733233
TI  - [Exhaustion and fatigue impair nearly all cancer patients--symposium in Basel
      presents important references].

PMID- 14733234
TI  - European Society of Endodontology 11th Biennial Congress. Athens, Greece, 2-4
      October 2003. Abstracts.

PMID- 14733235
TI  - [Bibliography of Polish literature on forensic medicine, criminology and related
      fields published in 2001].

PMID- 14733236
TI  - Ethics in oncology. Stormy weather ahead, but also the promise of a better world.

PMID- 14733238
TI  - A new hospital breaks ground.

PMID- 14733239
TI  - A gift of customer complaints.

PMID- 14733240
TI  - Learning from online communities.

PMID- 14733241
TI  - Get the word out. A multimedia approach helps showcase a new facility.

PMID- 14733242
TI  - To DTC or not to DTC? Direct-to-consumer advertising can seem like a prescription
      for futility.

PMID- 14733243
TI  - [Advances in pharmacological study of Leonurus heterophyllus Sweet].

PMID- 14733244
TI  - [Evidence based therapy for adult sleep apnea and nasal obstruction].

PMID- 14733245
TI  - [HIV-naive patients respond to pegylated interferon].

PMID- 14733246
TI  - Burn and Reconstructive Surgery Clinic. Faculty Hospital of the Masaryk
      University in Brno--20 years.

PMID- 14733247
TI  - First international convention following terror attacks of September 11, 2001.

PMID- 14733248
TI  - Importance of specialized departments for the treatment of burns.

PMID- 14733249
TI  - Successful treatment of a critically burned patient (case report).
AB  - The objective of this study was to document that treatment of a critically burned
      patient could be, although with some problems, ultimately very successful. The
      commonplace of such successful therapy is certainly not only current, up-to-date
      and most intensive care, but also good teamwork and professionalism of the whole
      team in the specialized workplace--Burn and Reconstructive Surgery Departments of
      the Faculty Hospital in Brno.

PMID- 14733250
TI  - Pain management in children with burn injuries.
AB  - Thermic injury is always associated with pain. The objective of authors was to
      create algorithm of analgesia for children with burn injuries during pre
      hospitalization and hospitalization.

PMID- 14733251
TI  - Unusual course of treatment of a patient diagnosed with Pemphigus Vulgaris (case
      report).
AB  - The case report is describing patient with an autoimmune disease, Pemphigus
      Vulgaris. This patient arrived to the general practitioner with Pemphigus
      Vulgaris after 20 days from the first manifestation of the disease. Despite
      intensive care, patient dies forty-seventh day after first clinical manifestation
      of the illness of candidemia. Candidiasis was diagnosed only in postmortem
      examination.

PMID- 14733252
TI  - The influence of moisture wound healing on the incidence of bacterial infection
      and histological changes in healthy human skin after treatment of interactive
      dressings.
AB  - In this article the authors discuss the problem faced by physicians when trying
      to use moisture-retentive dressing in pressure sores (decubitus ulcers). First,
      they report the results of an in vitro study using a new model of experimental
      wound (radio-isotopic investigation) that assesses the release of Ringer's
      solution from interactive dressings continually during fourteen hours. Second,
      they perform an animal experiment that assesses the incidence of wound infection
      in defects treated conventionally or using interactive dressings. The defects
      treated with interactive pads had lower incidence of wound infection, and the
      process of wound healing was rapid. Finally, the authors discuss their experience
      in four paraplegic patients with decubitus ulcers where they used moisture
      retentive dressing on ulcers and on the surrounding intact skin before surgical
      procedure to detect the possibility of maceration of healthy skin. Histological
      evaluation was performed in order to find microscopically changes after moisture
      healing. The changes of healthy skin were not significant after treatment of
      moisture-retentive dressings.

PMID- 14733253
TI  - Endocrine changes after burns: the bone involvement.
AB  - Any major burn is followed by a pronounced endocrine and metabolic response, by
      an acute phase response. In 30 burn subjects whose bone status was studied after
      burn trauma with the densitometer HOLOGIC 2000, bone involvement was found 6 and
      12 months postburn: the Bone Mineral Density (BMD) of their lumbar vertebrae L1-4
      and of their left hip dropped significantly in most of them. Elevated levels of
      cortisol both in blood and in urine (free cortisol) were found, accompanied by
      very low testosterone, dihydrotestosterone (DHT) and free testosterone levels in
      blood of the burned males, but not of the females. Elevated 17beta-estradiol
      levels were found in many burned males; they were generally not low in the burned
      females. DHEA-S levels were generally low. Very low levels of the
      triiodothyronine (T3) and of the free thyroxine (FT4) were found. Increased, even
      very high, PTH values were occasionally present. hGH and IGF-1 were generally
      normal, with a few exceptions (low or increased levels). Total and ionized
      calcium levels were low after burn, 250H vitamin D (calcidiol) was usually low or
      low normal too. Prolonged and very high levels of CTX and of NTX (both are
      indicators of bone resorpcion, of collagen catabolism) were found, as well as of
      the ACP (acid phosphatases), but the latter were less manifest, if compared with
      the CTX and NTX. ALP (alkaline phosphatases) were elevated too, but their
      elevated levels were much less pronounced than the levels of CTX and NTX.
      Osteocalcin levels were initially low to low normal, to increase later to the
      normal levels. As for the cytokines that had been investigated, mostly the
      elevated levels of TNFalpha were found, as well as those of IL-2, IL-6 and IL-8.
      Finally, a few suggestions have been given regarding the additional possibilities
      how to treat the burned patients: the use of anabolics, of vitamin D, of calcium,
      eventually of calcitonin.

PMID- 14733254
TI  - Award of the G. Whitaker International Burns Prize for 2003 Palermo, Italy.

PMID- 14733255
TI  - Depth of the graft bed influences split-skin graft contraction.
AB  - Contraction of a split-thickness skin graft used for coverage of large defects
      remains a great problem in plastic, burn and reconstructive surgery. In this
      study we evaluated healing of split-thickness skin grafts transplanted in wounds
      on the subcutaneous fat and muscle fascia in pigs. Four young domestic female
      pigs were included in the study, and the contraction was measured planimetrically
      during a 3-months' follow-up. At the end of the study the scar tissue was
      histologically assessed. From day 42 till the end of the study grafts
      transplanted on the muscle fascia were significantly more contracted than grafts
      on the subcutaneous fat without (p < 0.001) and with (p < 0.005, unpaired t-test)
      correction for the growth of the animal. The histological assessment showed that
      after 3 months the regenerated dermal tissue in the muscle fascia wounds was
      thicker, and less remodeled (higher tissue cellularity and thinner collagen
      bundles). In conclusion, in pigs, split-thickness skin grafts transplanted into
      deeper wounds contract more, and scar tissue maturation seems to last longer.

PMID- 14733256
TI  - Testing intestinal permeability in rats with burns and administration of early
      enteral nutrition.
AB  - Damaged intestinal mucosa in patients with extensive burns is one of the causes
      of the development of SIRS and MOFS. No unequivocal method has been established
      so far for assessment of the extent of damage of the intestinal mucosa. In the
      presented work the authors focus their attention on assessment of intestinal
      permeability in rats with burns. As their experimental method they used the
      lactulose-mannitol test (LAMA test). The animals were subjected to a deep burn
      with an extent of 20% body surface (TBSA). Then the LAMA test was performed 24,
      48 and 72 hours after the burn. The rats were divided into groups: the first with
      a burn without enteral nutrition, the second with a burn and polymeric enteral
      nutrition and the last with oligomeric enteral nutrition. From the conclusions it
      is evident that a burn extending over 20% TBSA causes in the laboratory rat to
      experience impaired intestinal permeability. The work did not prove a significant
      difference between groups with and without enteral nutrition. Due to its
      simplicity speed, repeatability and high yield the LAMA test is a method which
      can be used in patients with burns in departments for the treatment of burns.

PMID- 14733257
TI  - Regarding "The failure of dentistry's social contract with America and
      California's search for legislative solutions".

PMID- 14733258
TI  - State financing of dental education: impact on supply of dentists.
AB  - In 2000, the thirty-six states with public dental schools provided an average
      subsidy of 49,347 dollars per dental student. In contrast, nineteen states
      provided little or no subsidy. Since states invest in dental education, in part,
      to ensure an adequate supply of dentists, we examined the factors that explain
      dentist variation among states. We found that population size, per capita income,
      and the number of students from the state enrolled in dental school had a
      significant and positive impact. The level of state support for dental education
      and the presence of a dental school had a negative or nonsignificant effect,
      respectively. Apparently, dentists locate based primarily on the demand for their
      services and, to a lesser extent, on where they were raised. The states'
      investment in dental education had little impact on number of dentists because
      some states had many dentists but invested little in dental education. We
      identified two states that collectively account for 15 percent of enrolled
      students even though they provide minimal subsidy for dental education. We
      discuss the implications of these findings for states that do not have dental
      schools and need more dentists. This research was supported in part by grants
      from the Connecticut Health Foundation (Dental Workforce in Connecticut: Issues
      and Options), the Robert Wood Johnson Foundation, and the California Endowment
      (Pipeline, Profession, and Practice: Community-Based Dental Education).

PMID- 14733259
TI  - Confirming the validity of Part II of the National Board Dental Examinations: a
      practice analysis.
AB  - Successful completion of Part II of the National Board Dental Examinations is a
      part of the licensure process for dentists. Good testing practice requires that
      the content of a high stakes examination like Part II be based on a strong
      relationship between the content and the judgments of practicing dentists on what
      is important to their practice of dentistry. In an effort to demonstrate this
      relationship for Part II, the Joint Commission conducted a practice analysis,
      which involved a two-dimensional model. The sixty-three Competencies of the New
      Dentist, developed and promulgated by the American Dental Education Association,
      were used for one dimension, and the current content specifications were used for
      the other. A survey of 520 practicing dentists was conducted to determine the
      importance of each of the competencies for patient care. These dentists were
      recent graduates of accredited programs and passed Part II three to five years
      prior to the conduct of the practice analysis. The survey directed the
      respondents to rate the importance of the competencies on a scale from 1 to 5. Of
      the 520 in the sample, 244 dentists responded. The reliability index was above
      0.90. The importance rating for each competency was translated into the
      associated number of items. The number of items devoted to each competency was
      allocated to the current content elements that are related to the knowledge and
      problem-solving skills that support each competency. The findings specified
      revisions in the relative number of items dedicated to the various elements in
      the specifications. These findings indicate that the items on the examination
      under the current distribution adequately reflected practice. In general, there
      were relatively small changes in the content specifications. The total number of
      changes in items was forty-eight, which represents changes in slightly less than
      10 percent of the overall number of items.

PMID- 14733260
TI  - Clinical curriculum for the twenty-first century.

PMID- 14733262
TI  - Developing a group practice comprehensive care education curriculum.
AB  - In fall 2002 the University of Illinois at Chicago College of Dentistry
      implemented a Group Practice Comprehensive Care Clinical Education Curriculum.
      The primary responsibility for patient care has shifted in this comprehensive
      care curriculum from the students to the faculty and staff. Students have a
      primary responsibility for learning. This competency-based education curriculum
      utilizes a variety of student evaluation methods including self-evaluation, OSCE,
      and portfolio to verify competence. Formative evaluation methods are utilized in
      daily assessment of student performance. On-time graduation rates have increased
      from 60-70 percent to 96 percent, and regional board first-time pass rates have
      been maintained at 90+ percent. Overall predoctoral clinical productivity in the
      first full year of the program has increased by over 300,000 dollars.

PMID- 14733261
TI  - Predoctoral clinical curriculum models at U.S. and Canadian dental schools.
AB  - In fall 2002, the ADEA Section on Comprehensive Care and General Dentistry
      conducted a survey of the predoctoral clinical curriculum models at sixty-four
      North American dental schools. Fifty-eight percent of the schools reported that
      most patient care is provided in a comprehensive care clinic setting, 22 percent
      reported that most patient care is provided in discipline-specific settings, and
      20 percent reported a hybrid of comprehensive care and discipline-specific
      settings. While ten Primarily Discipline-Based (PD) schools have instituted new
      Primarily Comprehensive Care (PCC) or Hybrid clinical curricula since 1997, one
      PCC school has converted to a Hybrid model, and one PCC school has converted to a
      PD model. PCC curriculum models were frequently associated with the following
      institutional factors: more densely populated metropolitan areas; private
      institutional sponsorship; location within a university medical center; larger
      class size; and more students enrolled in advanced training at the school.
      Curriculum factors frequently associated with PCC models included the following:
      increased use of simulation technology: higher proportion of clinical/teaching
      track faculty; higher proportion of part-time faculty; higher proportion of
      generalist faculty; same faculty supervising both treatment planning and patient
      treatment; and use of competency exams as the main requirement for completion of
      the curriculum.

PMID- 14733263
TI  - A new school's perspective on clinical curriculum.
AB  - The new predoctoral dental education program at the University of Nevada, Las
      Vegas, officially began on August 26, 2002. Key concepts identified as
      foundations for the UNLV clinical curriculum model include Student Active
      Integrated Learning (SAIL), the need to actively link oral health to systemic
      health, a sophisticated practice management model, a focus on culturally
      sensitive statewide outreach, establishing a strong biomedical research base, and
      development of future faculty. The predoctoral program will be comprised of five
      general practices. Students from each of the four academic years will be assigned
      to a practice group; each student will be expected to provide patient care within
      the scope of his or her current training.

PMID- 14733265
TI  - Oral health disparities among the elderly: interdisciplinary challenges for the
      future.
AB  - The elderly, like other population groups, have experienced varying levels of
      oral health among their diverse demographic subgroups. For those in poverty,
      experiencing social isolation, residing in long-term care institutions, and with
      complex medical illness, oral health care may be unreachable. Various models of
      training, education, and community, public, and professional collaboration have
      been proposed, yet few strategies have been implemented. Interdisciplinary
      approaches that bring interested partners together as equal stakeholders may
      create faster tracks in improving access to health care for those geriatric
      patients who lack it. This article explores past and present recommendations for
      interdisciplinary collaborations, reviews the current and future needs of the
      geriatric population, discusses educational models and content, and expresses the
      need for leadership to address oral health disparities in the elderly. Finally,
      strategies for making improvements in the existing oral health disparities are
      discussed.

PMID- 14733264
TI  - Addressing health disparities through dental-medical collaborations, part II.
      Cross-cutting themes in the care of special populations.
AB  - This article introduces the second group in a series of articles in this journal
      on dental-medical collaborations to reduce oral health disparities. This group
      targets the needs of the elderly and individuals with mental retardation,
      developmental disabilities, and other special health problems. Five themes are
      common to these populations: the importance of oral-systemic interactions and
      need for interprofessional collaboration in care and training; the possibility of
      diminished mental and motor capacities and ability to provide self-care;
      difficulty accessing appropriate dental care; complex social and cultural
      factors; and the lack of a sufficient evidence base on basic mechanisms and
      clinical interventions. Gaps in training of dental, medical, and other health
      professionals contribute to disparities. Few programs provide integrated,
      interdisciplinary approaches, despite the growing numbers of elderly and the
      increasing life span of individuals with developmental disabilities. The
      inability of many such individuals to advocate for themselves, limitations in
      financial mechanisms, and societal biases fuel health disparities. These articles
      propose recommendations for key changes in dental and other health professional
      training, advocate increased commitment to special populations in research
      agendas, and encourage collaboration across health professions and with community
      and advocacy groups. A strong emphasis on prevention must be a part of these
      changes.

PMID- 14733266
TI  - The American Academy of Developmental Medicine and Dentistry: eliminating health
      disparities for individuals with mental retardation and other developmental
      disabilities.
AB  - Recent reports by Special Olympics International and the U.S. Surgeon General
      have revealed significant disparities and unmet health needs encountered by
      persons with mental retardation and other developmental disabilities (MR/DD).
      Factors contributing to these disparities include deinstitutionalization,
      increased survival of individuals with MR/DD, lack of appropriately trained
      providers, and inadequate financing of dental services. To address these
      problems, a group of academically oriented dentists and physicians formed the
      American Academy of Developmental Medicine and Dentistry (AADMD). The mission of
      the AADMD is to improve the quality of health services provided to persons with
      MR/DD by improving dental and medical school-based training of dentists and
      enhancing clinically relevant research. A central theme of the AADMD is full
      collaboration between physicians and dentists in meeting its goals. The National
      Action Strategy developed by the AADMD focuses on creating a series of university
      based Developmental Medicine and Dentistry Programs (UDMDPs) in medical and
      dental schools, which collaborate in service, teaching, and research with
      community-based primary care clinics, community hospitals, intermediate care
      facilities, and other private service delivery systems such as the Special
      Olympics Healthy Athletes Program that serve these patients. Oral-systemic
      interactions will receive special emphasis by the training and research programs.

PMID- 14733267
TI  - CASE STUDIES for Dentistry: development of a tool to author interactive,
      multimedia, computer-based patient simulations.
AB  - Computer-based patient simulations have been used to enhance the dental
      curriculum since the 1980s. This article describes the development of CASE
      STUDIES for Dentistry (CSD), a patient case simulation building template,
      developed at Virginia Commonwealth University, with which authors who have no
      programming expertise can create realistic, effective, interactive multimedia
      patient simulations by entering their own information and images into a
      straightforward, fill in the blanks interface. This program was written with
      Authorware, by Macromedia Inc. Design considerations included emphasis on
      information collection and analysis, synthesis of collected information,
      hypothesis proposal and testing, diagnosis, and treatment planning. The program
      consists of easily accessible interfaces for both authors and students. Authors
      build simulated patients using typed-in text and their own images. Faculty can
      build computer-based simulated patients so that students can immediately practice
      what they learn in class within a simulated doctor-patient relationship. CSD
      allows building simulations ranging from simple to complex patients in multiple
      disciplines. Robust feedback and other features allow students to learn both
      process and content in a self-directed, interactive environment.

PMID- 14733268
TI  - Automated external defibrillator use among the general population.
AB  - Automated External Defibrillators (AED) are becoming more prominent in public
      locations within the mainstream of our society. They are marketed as providing
      the ability for a broader range of people, beyond clinicians and community
      emergency medical services personal, to successfully defibrillate a person in
      cardiac arrest. The objectives of this study were to determine whether or not a
      member of the general population, without previous exposure to an AED, could
      successfully operate an AED, thus delivering the necessary shock in ventricular
      fibrillation arrest. In addition, we analyzed the relationship between health
      care training and the time required to defibrillate a patient using an AED and
      investigated the overall success of operating an AED with respect to health care
      training. Utilizing an AED trainer, we conducted a timed trial study of five
      subject categories (general population; first-year dental students; third-year
      dental students; dentists, hygienists, and nurses; and anesthesiologists and
      surgeons) as each operator attempted to defibrillate a mannequin (n=50). Their
      times, success in defibrillation, and comments were recorded. The general
      population group experienced an 80 percent failure rate, while the other groups
      showed an inverse relationship between failure rates and the amount of health
      care training. Overall, only 58 percent of the subjects successfully performed
      the defibrillation with the AED. Operator speed in relation to the amount of
      health care training showed another inverse relationship as times decreased from
      group one (general population) to group five (anesthesiologists and surgeons).
      The findings suggest that prior exposure to an AED leads to a greater number of
      successful defibrillations. It remains unclear at this time as to whether a
      member of the general population can successfully operate an AED.

PMID- 14733269
TI  - Epizootiologic and ecologic investigations of European brown hares (Lepus
      europaeus) in selected populations from Schleswig-Holstein, Germany.
AB  - From 1997-99 European brown hare (Lepus europaeus) population densities were
      estimated by spotlight surveys within different areas in Schleswig-Holstein,
      Germany. These areas showed a wide variation in local hare population densities.
      In addition, red fox (Vulpes vulpes) densities were estimated in 1997 by surveys
      of fox dens and litters. Sera of 321 hares (shot between 1998-2000) from four
      study areas were examined for antibodies against European brown hare syndrome
      virus (EBHSV) by enzyme linked immunosorbent assay (ELISA), Yersinia spp. (n =
      299) and Francisella tularensis (n = 299) by western blotting, Brucella spp. by
      Rose Bengal test, and Toxoplasma gondii by Sabin-Feldman test (n = 318). Tissue
      samples comprising lung, liver, spleen, kidney, heart, and adrenal glands were
      collected for histopathology. Liver (n = 201) and spleen (n = 201) samples were
      processed for the detection of T. gondii-antigen in tissue sections and 321 liver
      and spleen samples were investigated for EBHSV-antigen by ELISA. Furthermore, 116
      hares were examined macro- and microscopically for lungworms. Significant
      negative correlations between hare and fox densities were found in spring and
      autumn 1997. Antibodies against EBHSV were detected in 92 of 321 (29%), against
      Yersinia spp. in 163 of 299 (55%), and against T. gondii in 147 of 318 (46%)
      hares. We evaluated the potential influence of origin and hunting season on
      exposure rates of hares using logistic regression analysis. A strong association
      between hare densities and exposure rates was observed for various agents. One
      hundred and eight of 201 (57%) hares were positive for T. gondii-antigen. All
      sera were negative for antibodies against Brucella spp. and F. tularensis and all
      lung samples were negative for lungworms. In conclusion, variation in red fox
      densities may have an impact on the hare populations examined and the infectious
      diseases we studied seem to play a subordinate role in the dynamics of European
      brown hare populations from Schleswig-Holstein.

PMID- 14733270
TI  - Pathogens of house mice on arid Boullanger Island and subantarctic Macquarie
      Island, Australia.
AB  - Studies on island populations of house mice (Mus domesticus) and their viruses
      reveal insights into viral persistence in isolated communities. We surveyed the
      ectoparasites, endoparasites, and antiviral antibodies for 11 murine viruses and
      two bacteria of house mice inhabiting two islands off Australia. House mice on
      Boullanger Island were seropositive to two viruses, murine cytomegalovirus and
      epizootic diarrhea of infant mice. On subantarctic Macquarie Island, house mice
      were seropositive for five viruses: murine cytomegalovirus, lymphocytic
      choriomeningitis virus, mouse parvovirus, epizootic diarrhea of infant mice, and
      Theiler's murine encephalomyelitis virus. The diversity of antiviral antibodies
      was lower among populations of house mice on islands than those inhabiting
      mainland Australia. The decreased diversity of viruses in island populations of
      house mice may be a function of which agent the founder mice transfer to the
      island and related to the low densities which the host population may
      periodically reach over time.

PMID- 14733271
TI  - Infectious disease survey of gemsbok in New Mexico.
AB  - Exotic wildlife can introduce new diseases or act as reservoirs of endemic
      diseases. On White Sands Missile Range, New Mexico (USA), significant declines in
      populations of native ungulates generally correspond to increases in range and
      population density of the exotic gemsbok (Oryx gazella gazella), introduced
      beginning in 1969. We surveyed gemsbok in 2001 for exposure to a variety of
      diseases potentially important for native ungulates. High seroprevalence was
      found for malignant catarrhal fever virus (49 [98%] of 50 sera; 43 [96%] of 45
      plasma samples), blue-tongue virus (48 [96%] of 50), bovine respiratory syncytial
      virus (33 [66%] of 50), and parainfluenza-3 virus (10 [20%] of 50). Low numbers
      of Nematodirus spp. eggs in a few individuals were the only parasites detected in
      gemsbok. Exposure to the above diseases in gemsbok is of interest to managers
      because of potential implications for recovery of desert bighorn sheep (Ovis
      canadensis mexicana) and desert mule deer (Odocoileus hemionus crooki) in the
      White Sands area because each has been implicated in mortality in these species
      either in the White Sands area or elsewhere in the western/southwestern United
      States.

PMID- 14733272
TI  - Antibodies to ruminant alpha-herpesviruses and pestiviruses in Norwegian cervids.
AB  - A serologic survey revealed that Norwegian populations of free-ranging reindeer
      (Rangifer tarandus tarandus), roe deer (Capreolus capreolus), red deer (Cervus
      elaphus), and moose (Alces alces) have been exposed to alpha-herpesviruses and
      pestiviruses. A total of 3,796 serum samples collected during the period 1993
      2000 were tested in a neutralization test for antibodies against bovine
      herpesvirus 1 (BHV-1) or cervid herpesvirus 2 (CerHV-2), and 3,897 samples were
      tested by a neutralization test and/or enzyme-linked immunosorbent assay for
      antibodies against bovine viral diarrhea virus (BVDV). Antibodies against alpha
      herpesvirus were found in 28.5% of reindeer, 3.0% of roe deer, and 0.5% of red
      deer, while all moose samples were negative. In reindeer, the prevalence of
      seropositive animals increased with age and was higher in males than females.
      Antibodies against BVDV were detected in 12.3% of roe deer, 4.2% of reindeer,
      2.0% of moose and 1.1% of red deer. The results indicate that both alpha
      herpesvirus and pestivirus are endemic in reindeer and pestivirus is endemic in
      roe deer in Norway. The viruses may be specific cervid strains. Seropositive red
      deer and moose may have become exposed as a result of contact with other ruminant
      species.

PMID- 14733273
TI  - Toxoplasma gondii infections in captive black-footed ferrets (Mustela nigripes),
      1992-1998: clinical signs, serology, pathology, and prevention.
AB  - An epizootic of toxoplasmosis occurred among 22 adult and 30 kit black-footed
      ferrets (Mustela nigripes) maintained under quarantine conditions at the
      Louisville Zoological Garden (Louisville, Kentucky, USA) in June, 1992. Black
      footed ferrets appear to be highly susceptible to acute and chronic
      toxoplasmosis. Clinical signs were observed in 19 adults and six kits and
      included anorexia, lethargy, corneal edema, and ataxia. Two adults and six kits
      died with acute disease. High antibody titers to Toxoplasma gondii were detected
      by latex agglutination and modified agglutination assay in 10 black-footed
      ferrets. One adult and six kits that died with acute clinical signs were
      necropsied and T. gondii-like organisms were found microscopically in multiple
      organs. Diagnosis of toxoplasmosis was confirmed by immunohistochemical staining
      with anti-T. gondii antibodies and by ultrastructural examination. Although the
      source of T. gondii for black-footed ferrets was not identified, frozen uncooked
      rabbit was the most likely source. Chronic toxoplasmosis resulted in the death of
      at additional 13 black-footed ferrets that were adults during the epizootic.
      Affected animals developed chronic progressive posterior weakness and posterior
      ataxia 6-69 mo after the epizootic began. Meningoencephalitis or
      meningoencephalomyelitis associated with chronic toxoplasmosis were identified at
      necropsy in all 13 ferrets. Precautions to prevent introduction of pathogens into
      the colony were insufficient to exclude T. gondii. Although toxoplasmosis may
      cause significant mortality in mustelids, the high mortality of black-footed
      ferrets in this epizootic was of concern due to their endangered status. This is
      the first detailed report of toxoplasmosis in black-footed ferrets.

PMID- 14733274
TI  - Characterization of Pasteurella multocida isolates from wetland ecosystems during
      1996 to 1999.
AB  - We cultured 126 Pasteurella multocida isolates, 92 from water and 34 from
      sediment samples collected from wetlands in the Pacific and Central flyways of
      the United States between 1996 and 1999. Most (121) of the isolates were P.
      multocida serotype 1, but serotypes 3, 3/4, 10, and 11 were also found. Many (82)
      of the isolates were further characterized by DNA fingerprinting procedures and
      tested in Pekin ducks for virulence. Almost all the serotype 1 isolates we tested
      caused mortality in Pekin ducks. Serotype 1 isolates varied in virulence, but the
      most consistent pattern was higher mortality in male ducks than in females. We
      found no evidence that isolates found in sediment vs. water, between Pacific and
      Central flyways, or during El Nino years had consistently different virulence. We
      also found a number of non-serotype 1 isolates that were avirulent in Pekin
      ducks. Isolates had DNA fingerprint profiles similar to those found in birds that
      died during avian cholera outbreaks.

PMID- 14733275
TI  - Pasteurella multocida from outbreaks of avian cholera in wild and captive birds
      in Denmark.
AB  - An outbreak of avian cholera was observed among wild birds in a few localities in
      Denmark in 2001. The highest mortalities were among breeding eiders (Somateria
      mollissima) and gulls (Larus spp.). Pulsed-field gel electrophoresis (PFGE) was
      conducted using ApaI and SmaI as restriction enzymes and restriction enzyme
      analysis (REA) using HpaII. The Pasteurella multocida subsp. multocida strain
      isolated from birds in this outbreak was indistinguishable from a strain that
      caused outbreaks in 1996 and 2003. Most isolates from domestic poultry had other
      PFGE patterns but some were indistinguishable from the outbreak strain. Among 68
      isolates from wild birds, only one PFGE and one REA pattern were demonstrated,
      whereas among 23 isolates from domestic poultry, 14 different SmaI, 12 different
      ApaI, and 10 different HpaII patterns were found. The results suggest that a P.
      multocida strain has survived during several years among wild birds in Denmark.

PMID- 14733276
TI  - Aerosol exposure of white-tailed deer (Odocoileus virginianus) to Mycobacterium
      bovis.
AB  - Tuberculosis due to Mycobacterium bovis affects both captive and free-ranging
      Cervidae in the United States. Various animal models have been developed to study
      tuberculosis of both humans and animals. Generally, tuberculosis is transmitted
      by aerosol and oral routes. Models of aerosol exposure of large animals to M.
      bovis are uncommon. In order to develop a reliable method of aerosol exposure of
      white-tailed deer (Odocoileus virginianus) to M. bovis, 12 healthy white-tailed
      deer, aged 8-10 mo, were infected by aerosol exposure to 2 x 10(5) to 1 x 10(6)
      colony forming units (CFU) (high close, n = 4) of M. bovis or 6 x 10(2) to 1.6 x
      10(3) CFU (low dose, n = 8) of M. bovis. Tuberculous lesions were more widely
      disseminated in (leer receiving the high dose, while lesions in deer receiving
      the low dose were more focused on the lungs and associated lymph nodes
      (tracheobronchial and mediastinal). Aerosol delivery of M. bovis to white-tailed
      deer results in a reliable manner of experimental infection that may be useful
      for studies of disease pathogenesis, immune response, mycobacterial shedding, and
      vaccine efficacy.

PMID- 14733277
TI  - Safety of revaccination of pregnant bison with Brucella abortus strain RB51.
AB  - From December 1998 through February 1999, a study was conducted in a Brucella
      infected bison herd to evaluate the safety of booster vaccination of adult bison
      (Bison bison) with 6 x 10(9) colony forming units (CFU) of Brucella abortus
      strain RB51 (SRB51) that had previously been vaccinated as yearlings with 1 x
      10(10) CFU of SRB51. Abortions or other adverse effects were not observed after
      SRB51 booster vaccination. At 10 wk after adult vaccination, pregnant and
      nonpregnant bison (n = 65) were randomly selected for bacteriologic sampling of
      targeted maternal tissues during abattoir processing. Fetal tissues were also
      sampled in pregnant bison. The SR351 recovered from tissue samples of eight of 48
      pregnant bison and none of 17 nonpregnant bison. In three of the eight culture
      positive bison, SRB51 was recovered from fetal tissues. In three additional
      bison, one pregnant and two nonpregnant, B. abortus biovar 1 field strain was
      recovered from internal iliac or supramammary lymphatic tissues. Results of this
      study suggest the possibility that the SRB51 vaccine can be safely used to
      booster vaccinate pregnant bison in a Brucella-infected bison herd. Our data also
      reaffirms the potential for B. abortus field strains to persist in bison until
      attainment of reproductive age, despite extensive use of vaccination and
      serologic testing.

PMID- 14733278
TI  - Effect of venipuncture site on hematologic and serum biochemical parameters in
      marginated tortoise (Testudo marginata).
AB  - Blood samples were obtained from the dorsal coccygeal vein and the brachial vein
      of five adult (four females and one male) and two subadult males of marginated
      tortoise (Testudo marginata) and hematologic and biochemical parameters were
      compared. Significant differences were found for red blood cell count,
      hematocrit, hemoglobin concentration, total proteins, uric acid, aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline
      phosphatase, calcium, and phosphorus, which were greater in the brachial vein
      samples. Hemodilution due to lymph was observed when collecting blood from the
      dorsal coccygeal vein, and it is thought to be the cause of the differences
      found. This research documented that the brachial vein is a more reliable and
      consistent venipuncture site than dorsal coccygeal vein in marginated tortoise.

PMID- 14733279
TI  - Clinical pathology and assessment of pathogen exposure in southern and Alaskan
      sea otters.
AB  - The southern sea otter (Enhydra lutris nereis) population in California (USA) and
      the Alaskan sea otter (E. lutris kenyoni) population in the Aleutian Islands
      (USA) chain have recently declined. In order to evaluate disease as a
      contributing factor to the declines, health assessments of these two sea otter
      populations were conducted by evaluating hematologic and/or serum biochemical
      values and exposure to six marine and terrestrial pathogens using blood collected
      during ongoing studies from 1995 through 2000. Samples from 72 free-ranging
      Alaskan, 78 free-ranging southern, and (for pathogen exposure only) 41
      debilitated southern sea otters in rehabilitation facilities were evaluated and
      compared to investigate regional differences. Serum chemistry and hematology
      values did not indicate a specific disease process as a cause for the declines.
      Statistically significant differences were found between free-ranging adult
      southern and Alaskan population mean serum levels of creatinine kinase, alkaline
      phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium,
      cholesterol, creatinine, glucose, phosphorous, total bilirubin, blood urea
      nitrogen, and sodium. These were likely due to varying parasite loads,
      contaminant exposures, and physiologic or nutrition statuses. No free-ranging sea
      otters had signs of disease at capture, and prevalences of exposure to
      calicivirus, Brucella spp., and Leptospira spp. were low. The high prevalence
      (35%) of antibodies to Toxoplasma gondii in free-ranging southern sea otters,
      lack of antibodies to this parasite in Alaskan sea otters, and the pathogen's
      propensity to cause mortality in southern sea otters suggests that this parasite
      may be important to sea otter population dynamics in California but not in
      Alaska. The evidence for exposure to pathogens of public health importance (e.g.,
      Leptospira spp., T. gondii) in the southern sea otter population, and the naivete
      of both populations to other pathogens (e.g., morbillivirus and Coccidiodes
      immitis) may have important implications for their management and recovery.

PMID- 14733280
TI  - A comparison of carfentanil/xylazine and Telazol/xylazine for immobilization of
      white-tailed deer.
AB  - October 2001 to January 2002, captive free-ranging white-tailed deer (Odocoileus
      virginianus) were immobilized with a combination of carfentanil citrate and
      xylazine hydrochloride. From this study, we selected a dose of
      carfentanil/xylazine for the purpose of comparing immobilization parameters and
      physiologic effects with those of a combination of tiletamine and zolazepam
      (Telazol) and xylazine. Animals were initially given intramuscular injections of
      10 mg xylazine and one of four doses of carfentanil (i.e., 0.5, 1.0, 1.5, and 2.0
      mg). A carfentanil dose of 1.2 mg (x +/- SD = 23.5 +/- 3.2 microg/kg) and 10 mg
      xylazine (0.2 +/- 0.03 mg/kg) were selected, based on induction times and
      previously published reports, to compare with a combination of 230 mg of Telazol
      (4.5 +/- 0.6 mg/kg) and 120 mg xylazine (2.3 +/- 0.3 mg/kg). Time to first
      observable drug effects and to induction were significantly longer for deer
      treated with carfentanil/xylazine than with Telazol/xylazine (P < 0.01).
      Hyperthermia was common in deer immobilized with carfentanil/xylazine, but heart
      rate, respiration rate, and hemoglobin saturation were within acceptable levels.
      Degree of anesthesia of deer immobilized with Telazol/xylazine was superior to
      deer immobilized with carfentanil/xylazine. The combination of 120 mg of
      naltrexone hydrochloride and 6.5 mg of yohimbine hydrochloride provided rapid and
      complete reversal (1.9 +/- 1.1 min) of carfentanil/xylazine immobilization.
      Animals immobilized with Telazol/xylazine had long recovery times with occasional
      resedation after antagonism with 6.5 mg of yohimbine. The combination of
      carfentanil and xylazine at the doses tested did not provide reliable induction
      or immobilization of white-tailel (leer even though drug reversal was rapid and
      safe using naltrexone and yohimbine.

PMID- 14733281
TI  - Capture of sandhill cranes using alpha-chloralose.
AB  - From 1990-2001, we made 188 successful captures of 166 different greater sandhill
      cranes (Grus canadensis tabida) through experimental use of alpha-chloralose
      (AC). Most captures took place during September (72.3%; n = 136), followed by
      August (14.9%; n = 28), and October (12.8%; n = 24). Territorial pairs were
      captured more successfully than family groups. Overall morbidity (6.4%) and
      mortality (4.3%) were lower than most other capture techniques for sandhill
      cranes. Exertional myopathy (EM) was the most common complication observed using
      AC (3.7%). Sedation level (chi5(2) = 25.9, P < 0.01) and month of capture
      (chi2(2) = 12.3, P < 0.01) were both associated with the presence of EM in cranes
      captured with AC. A logistic regression model suggests lighter sedation and the
      months of August and October are potential risk factors for EM in sandhill cranes
      captured with AC in Wisconsin (USA).

PMID- 14733282
TI  - Environmental and human demographic features associated with epizootic raccoon
      rabies in Maryland, Pennsylvania, and Virginia.
AB  - We assessed land use and demographic data as predictors discriminating between
      counties experiencing large or small first epizootics of rabies among raccoons
      (Procyon lotor). Monthly county reports of raccoons testing positive for rabies
      were obtained from rabies surveillance databases from Maryland, Pennsylvania, and
      Virginia (USA). Environmental and demographic data for the three states were
      obtained from public sources. On the basis of total reports of raccoon rabies
      during the first defined epizootic period, the 203 counties were dichotomized at
      the 75th percentile as having a large epizootic (> or = 24 rabid raccoons in the
      first epizootic) (51 counties) or a small epizootic or no epizootic (152
      counties). A high percentage of agricultural land use [OR = 9.1, 95% CI (3.6
      23.1)], high water coverage in combination with low human population density [OR
      = 8.8, 95% CI (2.9-27.0)], and low water coverage with high human population
      density [OR = 11.7, 95% CI (4.0-34.1)] were positively associated with large
      rabies epizootics. Counties with more than 15% of mixed forest were less likely
      to experience large epizootics than were counties with < or = 15% of mixed forest
      [OR = 0.3, 95% CI (0.1, 0.9)]. A combination of land use and human population
      density measures provided the best model for determining epizootic size and may
      be important predictors of epizootic behavior and risk of exposure to this
      reservoir species.

PMID- 14733283
TI  - Evidence of three new members of malignant catarrhal fever virus group in muskox
      (Ovibos moschatus), Nubian ibex (Capra nubiana), and gemsbok (Oryx gazella).
AB  - Six members of the malignant catarrhal fever (MCF) virus group of ruminant
      rhadinoviruses have been identified to date. Four of these viruses are clearly
      associated with clinical disease: alcelaphine herpesvirus 1 (AlHV-1) carried by
      wildebeest (Connochaetes spp.); ovine herpesvirus 2 (OvHV-2), ubiquitous in
      domestic sheep; caprine herpesvirus 2 (CpHV-2), endemic in domestic goats; and
      the virus of unknown origin found causing classic MCF in white-tailed deer
      (Odocoileus virginianus; MCFV-WTD). Using serology and polymerase chain reaction
      with (degenerate primers targeting a portion of the herpesviral DNA polymerase
      gene, evidence of three previously unrecognized rhadinoviruses in the MCF virus
      group was found in muskox (Ovibos moschatus), Nubian ibex (Capra nubiana), and
      gemsbok (South African oryx, Oryx gazella), respectively. Base on sequence
      alignment, the viral sequence in the muskox is most closely related to MCFV-WTD
      (81.5% sequence identity) and that in the Nubian ibex is closest to CpHV-2 (89.3%
      identity). The viral sequence in the gemsbok is most closely related to AlHV-1
      (85.1% identity). No evidence of disease association with these viruses has been
      found.

PMID- 14733284
TI  - Experimental infection of white-tailed deer (Odocoileus virginianus) with
      Ehrlichia chaffeensis by different inoculation routes.
AB  - The infection dynamics of the tick-transmitted organism Ehrlichia chaffeensis
      were investigated in white-tailed deer (Odocoileus virginianus) using different
      routes of inoculation. Six deer were each inoculated with 5.4 x 10(6) DH82 cells
      infected with E. chaffeensis (Arkansas strain) by three different routes:
      intravenous (n = 2), subcutaneous (n = 2), and intradermal (n = 2). Two control
      deer were inoculated with uninfected cells. Infections were monitored for 54 days
      and were continued in one deer from each E. chaffeensis inoculated group for an
      additional 31 days. All deer inoculated with E. chaffeensis seroconverted (> or =
      1: 64) and became 16S rDNA polymerase chain reaction and/or cell culture positive
      by post-inoculation day 15. There was no apparent (difference in susceptibility
      to infection between deer inoculated by different routes for the first 50 days
      based on detection of E. chaffeensis infection by PCR assay of blood or culture
      isolation. These results demonstrate infection of (deer by intradermal and
      subcutaneous routes for the first time.

PMID- 14733285
TI  - Health evaluation of pampas deer (Ozotoceros bezoarticus celer) at Campos del
      Tuyu Wildlife Reserve, Argentina.
AB  - Samples from 14 free-ranging pampas deer (Ozotoceros bezoarticus celer) were
      collected in 1995 and 1998, at Campos del Tuyu Wildlife Reserve, Buenos Aires,
      Argentina. Hematology, serum chemistries, minerals and metals, and fecal
      parasites were analyzed. In addition, fecal ova and parasites were evaluated
      seasonally during 1998-2000. Serology for infectious diseases included blue
      tongue, brucellosis, bovine respiratory syncytial virus infection, bovine viral
      diarrhea/mucosal disease, infectious bovine rhinotracheitis, Johne's disease
      (paratuberculosis), foot and mouth disease (FMD), leptospirosis (eight serovars),
      epizootic hemorrhagic disease, and parainfluenza-3 (PI-3). Three (21%) pampas
      deer had antibodies to Leptospira spp. and six (43%) to PI-3 virus. Serologic
      results for all other infectious agents were negative. Domestic cattle (n = 27)
      included in this study for comparison had antibodies to Leptospira, infectious
      bovine rhinotracheitis virus, bovine viral diarrhea virus, and PI-3 virus (74
      100% of tested animals) and one animal (4%) to Brucella sp. All cattle had
      antibodies to FMD virus attributable to vaccination. This study provides the
      first data on the health status of the southernmost sub-species of pampas deer.

PMID- 14733286
TI  - Serologic evidence of West Nile virus infection in black bears (Ursus americanus)
      from New Jersey.
AB  - Serum samples obtained from 51 free-ranging black bears (Ursus americanus) in
      northwestern New Jersey in February and March 2002 were analyzed for neutralizing
      antibodies to West Nile virus (WNV) and St. Louis encephalitis virus. Three (6%)
      of the black bears tested positive for WNV-neutralizing antibodies. One
      additional sample was positive for flavivirus-neutralizing antibodies but could
      not be differentiated for a specific virus type. This is the first report of WNV
      infection in black bears.

PMID- 14733287
TI  - Sharing of Pasteurella spp. between free-ranging bighorn sheep and feral goats.
AB  - Pasteurella spp. were isolated from feral goats and free-ranging bighorn sheep
      (Ovis canadensis canadensis) in the Hells Canyon National Recreation Area
      bordering Idaho, Oregon, and Washington (USA). Biovariant 1 Pasteurella
      haemolytica organisms were isolated from one goat and one of two bighorn sheep
      found in close association. Both isolates produced leukotoxin and had identical
      electrophoretic patterns of DNA fragments following cutting with restriction
      endonuclease HaeIII. Similarly Pasteurella multocida multocida a isolates
      cultured from the goat and one of the bighorn sheep had D type capsules, serotype
      4 somatic antigens, produced dermonecrotoxin and had identical HaeIII
      electrophoretic profiles. A biovariant U(beta) P.haemolytica strain isolated from
      two other feral goats, not known to have been closely associated with bighorn
      sheep, did not produce leukotoxin but had biochemical utilization and HaeIII
      electrophoretic profiles identical to those of isolates from bighorn sheep. It
      was concluded that identical Pasteurella strains were shared by the goats and
      bighorn sheep. Although the direction of transmission could not be established,
      evidence suggests transmission of strains from goats to bighorn sheep. Goats may
      serve as a reservoir of Pasteurella strains that may be virulent in bighorn
      sheep; therefore, goats in bighorn sheep habitat should be managed to prevent
      contact with bighorn sheep. Bighorn sheep which have nose-to-nose contact with
      goats should be removed from the habitat.

PMID- 14733288
TI  - Experimental Babesia gibsoni infection in coyotes (Canis latrans).
AB  - Four 5 mo old captive raised coyotes (Canis latrans) were experimentally
      inoculated with approximately 1 x 10(6) Babesia gibsoni organisms. Parasites were
      detected 1 wk post-inoculation in all coyotes with maximum parasitemia of 8-11%
      occurring at 34 wk. Parasitemias remained at or above 1% for at least 12 wk and
      were still detectable 20 wk post-inoculation. All experimentally infected coyotes
      developed pale mucous membranes, splenomegaly, and a positive heme reaction in
      urine while one coyote exhibited mild depression and inappetence. Infected
      coyotes also developed a regenerative anemia, thrombocytopenia, and neutropenia.
      The mild clinical signs coupled with the high level and long duration of
      parasitemia indicate that coyotes could serve as reservoirs for B. gibsoni.
      Entrance of this foreign parasite into the United States suggests the need for
      strict quarantines and thorough health and blood film examinations for imported
      animals.

PMID- 14733289
TI  - Canine parvovirus enteritis, canine distemper, and major histocompatibility
      complex genetic variation in Mexican wolves.
AB  - The endangered Mexican wolf (Canis lupus baileyi) was recently reintroduced into
      Arizona and New Mexico (USA). In 1999 and 2000, pups from three litters that were
      part of the reintroduction program died of either canine parvovirus or canine
      distemper. Overall, half (seven of 14) of the pups died of either canine
      parvovirus or canine distemper. The parents and their litters were analyzed for
      variation at the class II major histocompatibility complex (MHC) gene DRB1.
      Similar MHC genes are related to disease resistance in other species. All six of
      the surviving pups genotyped for the MHC gene were heterozygous while five of the
      pups that died were heterozygous and one was homozygous. Resistance to pathogens
      is an important aspect of the management and long-term survival of endangered
      taxa, such as the Mexican wolf.

PMID- 14733290
TI  - Bilateral uric acid nephrolithiasis and ureteral hypertrophy in a free-ranging
      river otter (Lontra canadensis).
AB  - We report the first case of uric acid nephrolithiasis in a free-ranging river
      otter (Lontra canadensis). A 7 yr old male river otter collected from the Skagit
      River of western Washington (USA) had bilateral nephrolithiasis and severely
      enlarged ureters (one of 305 examined [0.33%]). The uroliths were 97% uric acid
      and 3% protein. Microscopic changes in the kidney were confined to expansion of
      renal calyces, minor loss of medullary tissue, and multifocal atrophy of the
      cortical tubules. No inflammation was observed in either kidney or the ureters.
      The ureters were enlarged due to marked hypertrophy of smooth muscle plus
      dilation of the lumen. Fusion of the major calyces into a single ureteral lumen
      was several cm distal to that of two adult male otters used as histopathologic
      control specimens. This case report is part of a large contaminant study of river
      otters collected from Oregon and Washington. It is important to understand
      diseases and lesions of the otter as part of our overall evaluation of this
      population.

PMID- 14733291
TI  - Epidemiologic determinants of aural abscessation in free-living eastern box
      turtles (Terrapene carolina) in Virginia.
AB  - Epidemiologic determinants of 46 cases of aural abscessation in free-living
      eastern box turtles (Terrapene carolina) admitted to the Wildlife Center of
      Virginia (Virginia, USA) from 1991 to 2000 were evaluated. County human
      population density, year and season of admission, weight, and sex did not affect
      the risk for box turtles to develop aural abscessation. Counties with cases of
      aural abscessation were not randomly distributed, but rather were clustered into
      two multi-county regions. Geographic location was the only risk factor associated
      with aural abscessation in box turtles found in this study. Possible etiologies
      could include chronic infectious disease, malnutrition, or chronic exposure to
      environmental contamination with organochlorine compounds.

PMID- 14733292
TI  - Stem cells: reparative medicine and nephrology.
AB  - Stem cells (SC) provide a way to repopulate damaged organs, to deliver genes or
      growth factors to privileged sites in the body after gene transfection and to
      reconstitute organs in vitro for transplantation. This reparative or regenerative
      medicine is currently used in the care of hematological and neoplastic diseases,
      but promising results have been obtained in the care of other diseases involving
      heart, arteries, liver and brain. SC have also been used in experimental models
      of mice with glomerulonephritis or with unilateral uretheral obstruction. SC may
      be involved in the care of damaged organs in two ways. Firstly, niche cells
      reside in privileged regions of an organ and are protected from environmental
      damage; their reproduction is asymmetric, some of them self-generate and others
      differentiate in the specific tissue for organ repair. Secondly, SC from bone
      marrow, in which multiple distinct types are present, repair the damaged organ.
      Data from experimental animal models of renal diseases have shown that infused
      bone marrow-derived SC may repair the injured glomeruli. However, we cannot
      exclude that niche adult SC may reside in the outer medulla of the kidney.
      Therefore, niche cells may be the El Dorado for promising care for renal diseases
      in the near future.

PMID- 14733293
TI  - Altruistic living renal transplantation.
AB  - Living donor renal transplantation can not only reduce the increasing gap between
      demand and supply of renal transplants, but when compared with cadaveric renal
      transplants can also allow better results, particularly in the long-term. With
      the exception of HLA-identical siblings, there are no differences in long-term
      graft survival between HLA-related and HLA-unrelated living donor transplants.
      The possibility of a early transplantation, ideally before dialysis, can strongly
      improve patient and graft survival. The post-operative mortality and morbidity of
      the donor are minimal and may be furtherly reduced by an appropriate work-up. At
      present, there is no evidence that mononephrectomy in healthy subjects can expose
      them to an increased risk of renal failure, even in the long-term.

PMID- 14733294
TI  - The role of commercial non-related living kidney transplants.
AB  - The motivation for dialysis patients to seek early, even pre-emptive, kidney
      transplantation from living donors is discussed. In most countries both the
      waiting time and the numbers of patients awaiting kidney transplantation are
      increasing. Local geopolitics in Jerusalem have produced a unique window to
      observe present transplant practices which include widespread international
      marketing of kidneys from paid living donors. These have been subject of media
      admonitions and total rejection by professional organizations. In a modern world,
      traditional medical paternalism to both donors and patients should be balanced by
      rights for individual autonomy. Since patients, donors and medical professionals
      are already participating in illicit organ trading, is it not time for us to
      seriously consider the ethical and logistic implications of legalizing financial
      remuneration for kidney donation?

PMID- 14733295
TI  - Xenotransplantation, where do we stand?
AB  - Xenotransplantation is currently being investigated as a possible solution to the
      world-wide shortage of human organs. Several major advances have unquestionably
      been accomplished in the last decade in this field. These include an elucidation
      of the immunological mechanisms underlying the rejection of pig organs
      transplanted into primates, the generation of novel lines of genetically
      engineered pigs that are more "compatible" with man and a better understanding of
      the risk of zoonosis related to the transmission of porcine endogenous
      retroviruses to primates. Though very encouraging, the existing preclinical data
      do not entitle clinical trials with pig organs to begin as yet and, for the time
      being, the use of human organs remains the only viable option for patients with
      terminal organ failure.

PMID- 14733296
TI  - The future management of nephrology: budget elements and organization planning.
AB  - Like many specialized branches of medicine, the future of nephrology will be
      entrusted to organizational models that are able to withstand the impact of both
      the new and increasing demand for assistance and the rationalization of
      resources. Therefore, it is necessary to clearly understand that the model must
      integrate and unify many aspects that regulate the activities in the health care
      service. Budget means "who does what and with material and what human resources"
      with respect to the constraints imposed by the decisions of the controlling
      entities, and it is mainly a system of planning and control. Management control
      utilizes a combined and coordinated synthesis of various company techniques
      including an auditing system, analytical accounting (or per cents of cost), a
      reporting system able to change the data gathered into measures of syntheses that
      can be used to carry out sound evaluations. The health system needs a type of
      organization--typical of professional organizations--that is an absolute
      prerogative of the technical/professional component which is the only one able to
      discern, understand and propose new diagnostic and therapeutic trends and
      approaches. At the end an evaluation of quality system is depicted. ISO 9004
      norms, for example, provide principles on which an organization must be based, in
      order to reach high levels of quality and that must be used by the top management
      to lead the organization towards improved performance.

PMID- 14733297
TI  - The managerial future of nephrology and dialysis.
AB  - The work analyzes the present situation of hemodialysis centers in Campania
      Region, mainly highlighting the necessity of a Regional Health planning for all
      the chronic renal failure care centers in order to rationalize all economic
      resources, quality levels of health care and therapies.

PMID- 14733298
TI  - The future management of nephrology and dialysis.
AB  - This is a report of a combined experience of a nephrologist, who had been
      previously working for many years in a public hospital, and a business planning
      manager coming from a financial administration department of a multinational
      company. The Istituto Clinico Humanitas is a multi-specialist hospital
      accreditated with the National Health System, containing 473 beds available: 398
      inpatient, 28 intensive care and 47 day hospital beds. Human resources include
      approximately 250 medical doctors, 500 nurses and ancillary workers. In 2002 the
      hospital treated about 17,500 inpatients, 18,450 day hospital patients, nearly
      18,600 surgical interventions and 470,000 outpatients examinations and tests were
      performed. The detailed clinical activity of the general medicine and the
      nephrology units in 2002, the role of the scientific direction and that of the
      Humanitas Foundation have been presented. The work experience, in particular the
      advantages and disavantages of public versus private environment, represents
      another important topic of this paper.

PMID- 14733299
TI  - The role of extracorporeal therapies in sepsis.

PMID- 14733300
TI  - Blood glucose and lipid control as risk factors in the progression of renal
      damage in type 2 diabetes.
AB  - One of the central functions of the kidney is to excrete low molecular weight,
      water soluble, plasma, waste products into the urine, whereas macromolecules, the
      size of albumin and larger, are retained. The flow of the glomerular filtrate is
      thought to follow an extracellular route, passing through the endothelial
      fenestrae, then across the glomerular basement membrane and finally through the
      slit diaphragm between the foot processes of podocytes. Recently it has been
      hypothesized that microalbuminuria leading to proteinuria and to end stage renal
      disease (ESRD) is mainly due to an altered glomerular fitration barrier at
      podocyte level. The "conditio sine qua non" for the development of diabetic ESRD
      is hyperglycemia. However, arterial hypertension and abnormalities of blood lipid
      concentrations and structure are also an important antecedent of such
      complication in diabetes mellitus. Interestingly it has been suggested that
      hyperglycemia, arterial hypertension and dyslipidemia cause disorderes of albumin
      excretion rate by damaging podocyte and slit diaphragm protein scaffold with over
      production of and extracellular release of oxygen radical species at glomerular
      level. The present review will briefly discuss recent reports which describe the
      relationship between blood glucose and lipid abnormalities and the occurrence and
      progression of renal damage in diabetes mellitus. More particularly we will give
      evidence that the risk of a rapid decline of glomerular function abruptly
      increases when glycated hemoglobin is steadily higher than 7.5% and postprandial
      blood glucose is above 200 mg/dL. Eventually we will analyze recent reports
      showing that treatment with statins, the inhibitors of hydroxymethylglutaryl
      coenzyme A reductase, ameliorate the course of renal function in type 2 diabetic
      patients. It is not yet fully understood whether this effect is due to the
      lowering of the circulating levels of low density lipoproteins (LDL) or to an
      improved endothelial function or to lower patterns of LDL oxidation.

PMID- 14733301
TI  - Biofeedback in dialysis.
AB  - The traditional control of the dialysis session comes about by means of an open
      loop system. At the beginning of the session some parameters are set, such as the
      kind of dialyzer, the blood flow, the ultrafiltration rate, the dialysate
      conductivity and the dialysate temperature. Generally speaking, these parameters
      are not modified unless there occur complications in the patient that call for
      adjustments to be made. The biofeedback concept, which is synonymous with a
      closed-loop control of biological variables, presupposes, on the other hand: the
      continuous measurement of a variable thanks to a specific sensor its evaluation
      by a sort of expert system--the so-called controller and a series of means--the
      actuators--that allow the behavior of the variable to be directly or indirectly
      influenced. In clinical practice, different biofeedback systems are emerging,
      addressed to the control of blood volume, body temperature, and blood pressure.
      Each one of these systems has been successfully deployed, especially in the
      management of "difficult" patients unstable from the hemodynamic point of view.
      However, the future will be an integrated system that sees a complex adaptive,
      multi-input, multi-output controller which, with a great simplicity of use and
      low costs, will allow renal replacement therapy to be increasingly physiological
      and more efficient.

PMID- 14733302
TI  - On-line hemodiafiltration: technique and efficiency.
AB  - Hemodiafiltration (HDF) is the strategy enabling the high potential of hydraulic
      and solute permeability of synthetic membranes to be most properly exploited. On
      line production of unlimited amount of sterile dialysate at low cost has favored
      its extensive diffusion in the recent years. However, to achieve the most
      efficient convective transport, ultrafiltration rate must be forced towards its
      physical limits, paying attention to the safety of the patient and to the
      integrity of the system. The infusion mode variably influences the dialyzer
      performance and the efficiency of the technique. With respect to standard and
      high-flux hemodialysis (HD), increased removal of solutes in the small and middle
      molecular weight range was reported with on-line HDF in several recent studies.
      Some of these compounds have a pathogenic role or are markers of the most
      frequent long-term complications and causes of death in HD patients, such as
      dialysis related amyloidosis, cardiovascular disease, inflammation and
      malnutrition. Even in the absence of definite evidence, coming from large data
      base studies, there are strong indications to advise the use of this dialytic
      strategy, which combines the benefits of the high biocompatibility of the
      membrane and the sterile dialysis fluid with increased removal by convection of
      middle-molecular uremic toxins. A new mode of infusion in on-line HDF--the mixed
      infusion mode--is here described, which is able to achieve and maintain the
      maximum possible water and solute removal during the sessions through a feedback
      control of the transmembrane pressure.

PMID- 14733303
TI  - Long 3 x 8 hr dialysis: a three-decade summary.
AB  - A long hemodialysis (HD), 3 x 8 hours/week, has been used without significant
      modification in Tassin for 35 years with excellent morbidity and mortality
      results. It can be performed during the day or overnight. The relatively good
      survival is mainly due to a lower cardiovascular mortality than usually reported
      in dialysis patients. This in turn is mainly due to the good control of blood
      pressure (BP) including drug-free hypertension control and low incidence of
      intradialytic hypotension. This control of BP is probably the result of the tight
      extracellular volume normalization (dry weight), although one cannot exclude the
      effect of other factors such as serum phosphorus control well achieved using long
      dialysis. The high dose of small and even more of middle molecules is another
      essential virtue of long dialysis, leading to good nutrition, correction of
      anemia, control of serum phosphate and potassium with low doses of medications
      and providing a very cost-effective treatment. In 2002 one must aim at optimal
      rather than just adequate dialysis. Optimal dialysis needs to correct as
      perfectly as possible each and every abnormality due to renal failure. It can be
      achieved using longer (or more frequent) sessions. Overnight dialysis is the most
      logical way of implementing long HD with the lowest possible hindrance on
      patient's life. Due to the change in case mix a decreasing number of patients are
      able or willing to go on overnight dialysis, education to be autonomous is more
      difficult, but the benefit is still there.

PMID- 14733304
TI  - Optimizing PCR for clinical diagnosis.

PMID- 14733305
TI  - Current and emerging techniques for diagnostic mutation detection: an overview of
      methods for mutation detection.

PMID- 14733306
TI  - Mutation scanning for the clinical laboratory: DHPLC.

PMID- 14733307
TI  - Mutation scanning for the clinical laboratory-protein truncation test.

PMID- 14733308
TI  - Mutation scanning for the clinical laboratory: automated fluorescent sequencing.

PMID- 14733309
TI  - Comparative sequence analysis.

PMID- 14733310
TI  - Gene dosage analysis by multiplex amplifiable probe hybridization.

PMID- 14733311
TI  - Prenatal detection of chromosome aneuploidy by quantitative fluorescence-PCR.

PMID- 14733312
TI  - Fragile X disease.

PMID- 14733313
TI  - Huntington's disease.

PMID- 14733314
TI  - Hematological applications: hemoglobinopathies.

PMID- 14733315
TI  - Cystic fibrosis.

PMID- 14733316
TI  - Familial adenomatous polyposis.

PMID- 14733317
TI  - Multiple endocrine neoplasia types 1 and 2.

PMID- 14733318
TI  - Neurofibromatosis type 1: a common familial cancer syndrome.

PMID- 14733319
TI  - Duchenne and Becker muscular dystrophy.

PMID- 14733320
TI  - Spinal muscular atrophy.

PMID- 14733321
TI  - Quality management in molecular genetics.

PMID- 14733322
TI  - Regulation of genetic testing in clinical practice.

PMID- 14733323
TI  - Highlights of latest advances in antithrombotics.

PMID- 14733324
TI  - Antiplatelet, anticoagulant, and thrombolytic drug interactions.

PMID- 14733325
TI  - Evaluation of platelet antagonists in in vitro flow models of thrombosis.

PMID- 14733326
TI  - Heparin and low molecular weight heparin in thrombosis, cancer, and inflammatory
      diseases.

PMID- 14733327
TI  - Are low molecular weight heparins the same?

PMID- 14733328
TI  - Antithrombotic drugs for the treatment of heparin-induced thrombocytopenia.

PMID- 14733329
TI  - Laboratory methods for heparin-induced thrombocytopenia.

PMID- 14733330
TI  - Factor Xa inhibitors.

PMID- 14733331
TI  - Tissue factor/VIIa in thrombosis and cancer.

PMID- 14733332
TI  - Tissue factor pathway inhibitor in thrombosis and beyond.

PMID- 14733333
TI  - Cell adhesion molecules: potential therapeutic and diagnostic implications.

PMID- 14733334
TI  - Development and applications of animal models of thrombosis.

PMID- 14733335
TI  - A survey of venous thrombosis models.

PMID- 14733336
TI  - Arixtra (fondaparinux sodium).

PMID- 14733337
TI  - Oral thrombin inhibitor ximelagatran.

PMID- 14733338
TI  - Pharmacogenomics and coagulation disorders.

PMID- 14733339
TI  - Guidelines for diagnosis and treatment of deep venous thrombosis and pulmonary
      embolism.

PMID- 14733340
TI  - This is not a bill.

PMID- 14733341
TI  - Kinematic changes after fusion and total replacement of the ankle: part 1: Range
      of motion.
AB  - BACKGROUND: The purpose of this study was to determine how closely the present
      designs of ankle prostheses mimic the unique requirements of the foot and ankle.
      The three-dimensional range of motion (ROM) of the ankle joint complex, before
      and after ankle arthrodesis and after implantation of three currently used total
      ankle prostheses, was investigated. METHODS: The three-dimensional ROM was
      determined in six fresh-frozen cadaver leg specimens using a 6-df device with an
      axial load of 200 N and a four-camera high-speed video system. A moment of 100 Nm
      was applied to the footplate to determine the ROM in the sagittal (dorsiflexion
      and plantarflexion) and frontal (inversion and eversion) planes. The same moment
      was applied to the tibia to determine the ROM for the internal and external
      tibial rotation. The measurements were performed for the normal ankle, the fused
      ankle, and the AGILITY, HINTEGRA, and S.T.A.R. prostheses. RESULTS: Compared to
      the normal condition, the ROM for dorsiflexion and plantarflexion was changed for
      all surgical interventions. The changes were highest for the ankle arthrodesis.
      The changes due to the prostheses were significantly less than the changes due to
      ankle arthrodesis. Compared to the normal condition, the total ROM for
      inversion/eversion was slightly decreased by the fused ankle and not changed by
      the three-component prostheses (HINTEGRA, S.T.A.R.). However, the ROM for
      inversion/eversion was significantly higher for the two-component prosthesis,
      AGILITY. The ROM for internal and external tibial rotation was not altered by the
      AGILITY and HINTEGRA ankle, but it was significantly reduced by the ankle
      arthrodesis. S.T.A.R. showed a significant shift of the total ROM toward internal
      tibial rotation. CONCLUSIONS: The three tested ankle joint prostheses changed the
      ROM of the ankle joint complex less than ankle fusion did. Total ankle prostheses
      were shown to replicate normal joint ROM closely. However, ankle arthrodesis was
      found to reduce the ROM substantially in all three planes: the sagittal, frontal,
      and horizontal planes. CLINICAL IMPLICATIONS: With respect to the ROM, total
      ankle replacement changes the natural ankle joint condition less than ankle
      arthrodesis, which reduces the ROM in all three planes and might increase stress
      in adjacent structures. The prosthesis that replicated the normal ankle joint ROM
      best was the one with the most anatomical design.

PMID- 14733342
TI  - Kinematic changes after fusion and total replacement of the ankle: part 2:
      Movement transfer.
AB  - INTRODUCTION: The purpose of this in vitro study was to determine the
      biomechanical characteristics of the ankle based on the movement transfer between
      foot and leg before and after ankle arthrodesis, and after implantation of three
      currently used total ankle prostheses. METHODS: A 6-df device with an axial load
      of 200 N and a four-camera high-speed video system were used for the measurement
      of the range of motion in six fresh-frozen cadaveric leg specimens. While the
      foot was moved through the range of dorsiflexion/plantarflexion, the resulting
      foot eversion/inversion and tibial rotation were recorded. Analogously, the
      resulting foot eversion/inversion from tibial rotation and, vice versa, the
      resulting tibial rotation from foot eversion/inversion were determined. The same
      measurements were performed for the normal ankle, the fused ankle, and after
      total ankle replacement by the AGILITY, HINTEGRA, and S.T.A.R. prostheses.
      RESULTS: While in dorsiflexion/plantarflexion of the foot, ankle joint fusion
      increased the movement transfer to tibial rotation by a 2.4 factor and to
      eversion/inversion by a 18.5 factor, whereas, this movement transfer did not
      change for all prostheses conditions. The movement transfer between foot eversion
      and tibial rotation was found to decrease for all ankle prostheses, but more in
      the AGILITY and S.T.A.R. prosthesis than in the HINTEGRA. CONCLUSIONS: The three
      tested ankle joint prostheses changed the movement transferred within the ankle
      joint complex less than ankle fusion did, especially for
      dorsiflexion/plantarflexion movement of the foot. The closer the design was to
      the normal anatomy of the ankle, the closer the transfer of movement was shown to
      be replicated with respect to normal joint. It is suggested that success of total
      ankle arthroplasty depends on how successfully designs can mimic the movement
      transfer of the normal ankle, while dissipating the rotational forces and
      maintaining the stability of the joint.

PMID- 14733343
TI  - Kinematic changes after fusion and total replacement of the ankle: part 3: Talar
      movement.
AB  - INTRODUCTION: The purpose of this study was to determine talar movement (e.g.,
      talar rotation and talar shift during (dorsiflexion/plantarflexion) with respect
      to the tibia in the normal ankle, in the fused ankle, and in the replaced ankle
      by currently used prosthetic designs. METHODS: A 6-df device with an axial load
      of 200 N and a four-camera high-speed video system were used for the measurement
      of the range of motion in six fresh-frozen cadaveri leg specimens. While moving
      the foot through the whole range of motion for plantarflexion/dorsiflexion,
      segmental motion of the marked bones of the foot and shank were measured
      dynamically. Rotation and medial-lateral shift of the talus were then calculated
      with regard to flexion position of the foot. RESULTS: In the normal ankle,
      plantarflexion movement was coupled with talar inversion of 3.5 degrees, and
      dorsiflexion movement with talar eversion of 1.0 degree, in totally accounting
      for 4.5 degrees of talar rotation. While both the HINTEGRA and the S.T.A.R.
      prostheses did not show changes to the normal condition during the
      dorsiflexion/plantarflexion cycle (p < .05), talar rotation had a 60% decrease (p
      < .05) for the AGILITY prosthesis. In the normal ankle joint, a lateral talar
      shift of 1.4 mm was found to occur during dorsiflexion, and a lateral talar shift
      of 5.2 mm during plantarflexion. In both, the HINTEGRA and S.T.A.R. ankles, talar
      shift was converted into medial direction during dorsiflexion of the foot
      (difference to normal: p < .05), whereas talar shift in the lateral direction was
      found to occur during plantarflexion of the foot which was comparable to the
      normal ankle. The AGILITY ankle evidenced an 80% decrease of talar shift (p <
      .05) during the whole dorsiflexion/plantarflexion cycle. DISCUSSION: The two
      component ankle (AGILITY) obviously tends to restrict tremendously talar motion
      within the ankle mortise, whereas the three-component ankles (HINTEGRA, S.T.A.R.)
      seem to allow talar range of motion comparable to that in the normal ankle. It is
      suggested that such a restriction of talar motion results in an increase of
      stress forces within and around the prosthesis, leading to polyethylene wear and
      potential loosening at the bone-implant interfaces. Therefore, a successful
      prosthetic design for the ankle should consist of three components that are
      shaped as anatomically as possible to provide a normal range of motion and to
      allow the full transmission of movement transfer between foot and shank and
      unconstrained movement of the talus within the ankle mortise.

PMID- 14733344
TI  - Fracture of the polyethylene component in an ankle arthroplasty: a case report.
AB  - A 57-year-old female underwent total ankle arthroplasty for post-traumatic
      arthrosis using the Agility Total Ankle System. The talar component was placed in
      varus malalignment. Her postoperative course was remarkable for 19 months of
      satisfactory function followed by the acute onset of intense pain and decreased
      range of motion. There was no history of trauma. After failing a short course of
      observation, revision surgery of the arthroplasty was performed. Operative
      findings revealed a complete fracture of the polyethylene. This report details
      the first case of such a complication and discusses the importance of component
      alignment in the prevention of polyethylene insert failure.

PMID- 14733345
TI  - Recall of the risks of forefoot surgery after informed consent.
AB  - PURPOSE: To determine the number of risks a patient can recall from the informed
      consent process prior to surgery and if recall can be improved with a visual aid
      and to assess patient satisfaction with the informed consent process utilized.
      METHODS: Randomly selected patients, from all patients requiring forefoot
      surgery, were randomly assigned into two groups from August 2001 through October
      2001. All patients were asked to recall the risks of surgery and to rate their
      satisfaction with the informed consent process at their final routine
      postoperative visit. RESULTS: There were 19 patients in each group. All patients
      uniformly expressed their satisfaction with the preoperative informed consent
      discussion at their final visit. The mean number of the 11 risks recalled per
      patient was 1.0 for group A (range, 0-3) and 0.94 for group B (range, 0-4).
      CONCLUSION: At the final routine postoperative visit, patients in both groups had
      poor or no recall of the risks of surgery. The visual aid had no effect on
      improving recall.

PMID- 14733346
TI  - Reliability of isokinetic dynamometry in assessing plantarflexion torque
      following Achilles tendon rupture.
AB  - BACKGROUND: Research investigating the most effective management of Achilles
      tendon injury has been limited by a lack of reliable outcome measurements. Calf
      strength may be a valid outcome measure, not only in terms of identifying
      possible risk factors for reoccurrence of rupture, but also as an indicator of
      recovery. Isokinetic dynamometry has been suggested as an effective tool for
      measuring the torque of the calf muscles. Such measurements have demonstrated
      high reliability for the assessment of calf muscle torque in healthy subjects.
      However, there are no published data to demonstrate the reliability of isokinetic
      dynamometry in subjects with pathology in the Achilles tendon. The purpose of
      this study was to assess the inter- and intraobserver reliability of isokinetic
      dynamometry for assessing plantarflexion torque following Achilles tendon
      rupture. METHODS: Two independent observers used the Kin-com Dynamometer to
      measure the torque of the plantarflexors in 22 subjects 6 months after unilateral
      rupture of the Achilles tendon. Twelve subjects had been managed operatively and
      10 nonoperatively. Subjects were placed in the prone position with the knee
      extended. Measurements of peak torque, average torque, and total work were made
      for both concentric and eccentric plantarflexion movements at 60 degrees per
      second. RESULTS: Intraclass correlation coefficients were used to calculate
      reliability of measurements both within and between observers. Reliability was
      slightly greater on the healthy side (0.74-0.92 ICC) in comparison with the
      injured side (0.74-0.89 ICC). CONCLUSION: The results of this study suggest that
      isokinetic dynamometry provides a reliable method of measuring the torque of the
      plantarflexors following rupture of the Achilles tendon, with levels of
      reliability comparable with those from healthy subjects. The study concludes that
      this would be a valuable and reliable outcome measure for use in clinical trials.

PMID- 14733347
TI  - Symptom duration of plantar fasciitis and the effectiveness of Orthotripsy.
AB  - BACKGROUND: The use of surgically noninvasive application of Orthotripsy
      (extracorporeal shock waves) for various musculoskeletal disorders is being
      increasingly utilized. Because most patients have had prolonged symptoms
      refractory to nonoperative treatments, this study evaluated the effectiveness of
      electrohydraulic Orthotripsy for chronic proximal plantarfasciitis compared to
      the duration of symptoms prior to treatment. METHODS: Following evaluation for
      study inclusion (unresponsive symptoms for more than 6 months), qualified
      patients received Orthotripsy or placebo. The study patients were randomized per
      described protocol. Additional groups of nonrandomized patients also were
      studied. RESULTS: In both the randomized and nonrandomized patient groups, those
      who received Orthotripsy were slightly more likely to have a positive result
      (complete symptom relief or satisfactory improvement) if symptoms had been
      present and unresponsive to other nonoperative therapeutic attempts for less than
      2 years. The same trend was evident in patients undergoing a second Orthotripsy
      application. In the placebo group, there was no correlation between symptom
      duration and outcome. However, when placebo patients crossed over to the
      treatment arm of the study, the same response was evident: patients with symptoms
      for less than 2 years were slighty more likely to have a positive therapeutic
      response. Interestingly, the two patients with the longest duration of symptoms
      (15 and 18 years) both had complete symptom relief. CONCLUSIONS: The longevity of
      symptoms of chronic proximal plantar fasciopathy had a minimal impact on the
      likelihood of a positive response to Orthotripsy.

PMID- 14733348
TI  - Lateral shifting of the first metatarsal head in hallux valgus surgery: effect on
      sesamoid reduction.
AB  - Thirty feet with hallux valgus (HV) having grade 2 and 3 sesamoid stations on AP
      radiographs were examined after Lindgren-Turan oblique distal metatarsal
      osteotomy with a minimum follow-up of 12 months. Adductor tendon release from the
      lateral sesamoid was not performed to determine the isolated effect of distal
      metatarsal osteotomy on metatarsosesamoidal reduction. Of the 30 feet, 20 (67%)
      had reduced and 10 (33%) unreduced sesamoids at the follow-up. Ultimately, distal
      metatarsal osteotomy (DMO) with lateral shifting of the first metatarsal head
      more than 7.2 mm was found to reduce the sesamoids in the great majority of the
      cases (95% CI 7.243-9.757). Sesamoid release is redundant for metatarsosesamoidal
      reduction if sufficient lateral shift of the first metatarsal head over the
      sesamoids is accomplished.

PMID- 14733349
TI  - Effect of extracorporeal shock waves on calcaneal bone spurs.
AB  - In a prospective study of 435 patients with chronic proximal plantar fasciitis,
      283 (65%) had an inferior calcaneal bone spur of variable size evident prior to
      treatment with electrohydraulic high-energy extracorporeal shock waves (ESW).
      This included 308 patients who received extracorporeal shock wave treatments and
      127 placebo (sham control) patients. At both initial (3 months) and final (12
      months) evaluations after receiving ESW, no patient who received shock wave
      applications had significant disappearance or change in the radiographic
      appearance of the heel spur. Clinical outcome after ESW was satisfactory in 168
      patients (82%) with a radiographically demonstrable inferior heel spur and in 81
      patients (79%) without such a heel spur. The results showed no correlation
      between the presence or absence of the heel spur and the eventual treatment
      outcome.

PMID- 14733350
TI  - Flexor hallucis longus tendon transfer: evaluation of postoperative morbidity.
AB  - Clinical and pedobarograph evaluation was performed on 16 patients following
      flexor hallucis longus (FHL) tendon transfers to determine the resulting
      morbidity due to the loss of FHL function. All patients underwent FHL tendon
      transfer for either chronic tendon Achilles rupture or chronic Achilles
      tendinosis. Clinical evaluation of hallux function was performed using the
      American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal
      interphalangeal scale, the SF-36 score, and a clinical questionnaire to assess
      alteration in the clinical function of the hallux during activities of daily
      living. Pedobarography was carried out using the Musgrave pedobarograph system to
      detect changes in forefoot loading in comparison to the contralateral normal
      foot. Fourteen of the 16 patients scored maximally on the hallux
      metatarsophalangeal-interphalangeal scale and none of the patients noticed
      functional weakness of the hallux during activities of daily living at a mean
      follow-up of 43.6 months (range, 5-120 months). Pedobarograph readings showed a
      trend toward reduction in peak pressure loading on the distal phalanx, but this
      was not significant for the numbers of patients studied. There was no significant
      increase in loading of the first or second metatarsophalangeal joints to suggest
      that transfer metatarsalgia may complicate FHL tendon transfer. According to the
      results of the study morbidity from FHL transfer should be clinically
      insignificant.

PMID- 14733351
TI  - Lesser metatarsophalangeal joints: intra-articular distension, volumetric
      measurements, and changes of position.
AB  - Plantarflexion of the second metatarsophalangeal (MTP) joint with intra-articular
      injection has previously been observed and commented upon, and the purpose of
      this study was to determine motion of the lesser toes with direct fluid infusion
      into the lesser MTP joints. Fluid distension was found to cause variable postural
      changes in all lesser toes; the most consistent change was plantarflexion of the
      second metatarsophalangeal joint. Dorsiflexion of the third, fourth, and fifth
      MTP joints was observed, but less reliable than plantarflexion of the second MTP
      joint. The average volume in each of the lesser MTP joints was less than 1 cc.
      Plantarflexion of the second MTP joint was usually, but not always, indicative of
      intra-articular distention. Aspiration of these joints (given their small volume
      capacity) may not be a reliable or therapeutically useful technique.

PMID- 14733352
TI  - Use of computer-assisted learning module to achieve ACGME competencies in
      orthopaedic foot and ankle surgery.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) has charged
      academic institutions with finding methods to assess learning in specific areas
      of resident education. Computer-assisted education offers a reliable mode for
      teaching residents important information and skills. The CD-ROM "Fundamentals of
      Orthopaedic Foot Care," produced by the American Academy of Orthopaedic Surgeons,
      was tested as a tool to provide nonoperative foot and ankle care education for a
      group of orthopaedic residents (N = 14) and a group of family practice residents
      (N = 11). The CD-ROM's educational format includes an interactive tutorial on
      anatomy, video demonstrations on selected topics in physical examination and
      basic treatment of nonoperative problems of the foot and ankle, and patient
      education information sheets on multiple common foot disorders. Both resident
      groups scored significantly higher on their post-test exams after spending 1 hour
      with the computer program (p < or = .05). This study suggests that this program
      can be used reliably in an orthopaedic residency program to achieve ACGME
      required competency of "medical knowledge" in evaluation and nonoperative
      management of common foot and ankle problems.

PMID- 14733353
TI  - Open reduction for intra-articular calcaneal fractures: evaluation using computed
      tomography.
AB  - Radiographic and computed tomography features of unilateral intra-articular
      calcaneal fractures after open reduction and internal fixation were compared with
      late functional outcomes to identify prognostic factors. Sixty-one of 67 patients
      treated between 1997 and 2002 could walk painlessly postoperatively (average,
      19.7 months). Functional results (Laasonen's criteria) were excellent or good in
      92.5%. Factors associated with better functional results were lower age (p =
      .0227), greater Bohler angle at the time of injury (p < .0001), lower Sanders'
      grade (p = .0497), increased height of fractured regions (p = .0249), better
      reduction of the posterior facet (p = .0126), and better reduction of the
      calcaneocuboid joint (p = .0023). Only the latter two were found to be surgical
      prognostic factors.

PMID- 14733354
TI  - Glomus tumors in the foot: a new surgical technique for removal.

PMID- 14733355
TI  - Serum and aortic levels of phytosterols in rabbits fed sitosterol or sitostanol
      ester preparations.
AB  - Campesterol is present in all the phytosterol-containing dietary
      hypocholesterolemic agents in current use. Campesterol is absorbed more
      efficiently than sitosterol, and the question of its possible atherogenicity has
      been raised. To test this possibility, rabbits were fed either a semipurified,
      cholesterol-free diet that has been shown to be atherogenic for this species or
      the same diet augmented with 0.5 g of phytosterol-rich diet preparations
      (spreads) containing either sitosterol or sitostanol. The diets contained 295 mg
      phytosterol per 100 g. After 60 d, serum cholesterol levels in the two
      phytosterol groups were 78 +/- 4 mg/dL (sitosterol) and 76 +/- 4 mg/dL
      (sitostanol), respectively. The serum cholesterol level of rabbits fed the
      control diet was 105 +/- 8 mg/dL. Serum campesterol (microg/mL) levels were
      higher than sitosterol or sitostanol levels in all groups. Aortic phytosterols
      were present in nanogram quantities compared to cholesterol, which was present in
      microgram quantities. The ratio of campesterol/sitosterol/sitostanol in the
      aortas was: control, 1.00:0.43:0.02; sitosterol, 1:00:0.32:0.01; sitostanol,
      1:00:0.34:0.11. Aortic campesterol was present at 4% the concentration of aortic
      cholesterol, sitosterol at 1.4%, and sitostanol at 0.14%. Aortic lesions were not
      present in any of the animals.

PMID- 14733356
TI  - Comparison of the effects of dietary sunflower oil and virgin olive oil on rat
      exocrine pancreatic secretion in vivo.
AB  - The aim of this study was to investigate the functional consequences in vivo of
      adapting the rat exocrine pancreas to different dietary fats. Weanling rats were
      fed diets containing 10 wt% virgin olive oil or sunflower oil for 8 wk. We then
      examined resting and cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic
      secretion in the anesthetized animals. To confirm a direct influence of the type
      of fat upon the gland, the FA composition of pancreatic membranes as well as
      tissue protein and amylase content were determined in separate rats. The membrane
      FA profile was profoundly altered by the diets, reflecting the type of dietary
      fat given, although this was not paralleled by variations in the pancreatic
      content of protein or amylase. Nevertheless, dietary intake of oils evoked
      different effects on in vivo secretory activity. Resting flow rate and amylase
      output were significantly (P < 0.05) enhanced by sunflower oil feeding. Time
      course changes in response to CCK-8 infusion also showed a different pattern in
      each group. Secretion of fluid, protein, and amylase increased markedly in all
      animals, reaching a maximum within 20-40 min of infusion that was followed by a
      dramatic decline in both groups. In the sunflower oil group, this resulted in
      values reaching the resting level as soon as 60 min after CCK-8 infusion was
      begun. However, after the initial decline, olive oil group values showed a
      prolonged plateau elevation above the baseline (P < 0.05) that was maintained for
      at least the infusion time. In addition, a positive correlation between flow rate
      and both protein concentration and amylase activity existed in the olive oil
      group, but not in the sunflower oil group. The precise mechanism by which these
      effects are produced remains to be elucidated.

PMID- 14733357
TI  - Hyperphagia modifies FA profiles of plasma phospholipids, plasma FFA, and adipose
      tissue TAG.
AB  - Hyperphagia was achieved by continuous intracerebroventricular infusion of a
      melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats.
      The effects of hyperphagia on FA composition and concentration of plasma
      phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8
      d [short-term hyperphagia (STH); n = 8], or 28 d [long-term hyperphagia (LTH); n
      = 9]. The control rats were treated with artificial cerebrospinal fluid for 8 d
      (n = 8) or 28 d (n = 10). The rats were fed the same regular diet. In STH rats
      the plasma PL and fasting plasma FFA contained higher concentrations of saturated
      FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n-6 PUFA
      than in the control rats. In LTH rats the plasma PL contained higher
      concentrations of SFA, MUFA, and n-3 PUFA and higher proportions of 16:1n-7 and
      18:1n-9 at the expense of 18:2n-6 than in the control rats. In LTH rats the
      abundant dietary intake of 18:2n-6 did not enrich 18:2n-6 of the plasma PL or
      adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than
      twofold higher concentrations of SFA and MUFA, and higher proportions of 16:1n-7
      and 18:1n-9 at the expense of 18:2n-6 than in the control rats. This animal
      obesity model shows that LTH affects the FA composition and concentration of
      plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes
      associated with increased risk of various diseases in humans. These results also
      demonstrate that LTH alters the FA composition of plasma PL and adipose tissue
      TAG in a way that does not reflect the FA composition of dietary fat.

PMID- 14733358
TI  - cis-9,trans-11 and trans-10,cis-12 CLA affect lipid metabolism differently in
      primary white and brown adipocytes of Djungarian hamsters.
AB  - We explored whether CLA isomers and other C18 FA affect (i) lipid content and FA
      concentrations in total adipocyte lipids, (ii) FA synthesis from glucose in TAG
      and phospholipids of primary brown (BAT) and white adipocytes (WAT), and (iii)
      mRNA expression of uncoupling protein 1 (UCP1) in primary brown adipocytes of
      Djungarian hamsters (Phodopus sungorus). c9,t11-CLA, oleic, linoleic, and alpha
      linolenic acid increased whereas t10,c12-CLA decreased lipid accumulation in both
      adipocyte types. t10,c12-CLA treatment affected FA composition mainly in BAT
      cells. CLA incorporation into lipids, in particular c9,t11-CLA, was higher in
      BAT. In both cell types, t10,c12-CLA treatment reduced the incorporation of
      glucose 13C carbon into FA of TAG and phospholipids, whereas c9,t11-CLA,
      linoleic, and alpha-linolenic acid either did not influence or dose-dependently
      increased glucose carbon incorporation into FA. UCP1 mRNA expression was
      inhibited by t10,c12-CLA but increased by c9,t11-CLA, linoleic, and alpha
      linolenic acid. It is concluded that c9,t11-CLA and t10,c12-CLA have distinctly
      different effects on lipid metabolism in primary adipocytes. The effects of
      c9,t11-CLA are similar to those of other unsaturated C18 FA. The opposite effects
      of c9,t11-CLA and t10,c12-CLA are evident in both WAT and BAT cultures; however,
      brown adipocytes seem to be more susceptible to CLA treatment.

PMID- 14733359
TI  - Trans-18:1 isomers in rat milk fat as effective biomarkers for the determination
      of individual isomeric trans-18:1 acids in the dams' diet.
AB  - Female rats were fed a diet containing by weight 10% partially hydrogenated
      sunflower oil, 2% sunflower oil, and 1% rapeseed oil during gestation and
      lactation. The trans-18:1 isomer profile of the fat supplement was (in % of total
      trans 18:1 acids in the fat supplement): delta4, 0.5; delta5, 1.0; delta6-delta8,
      18.0; delta9 (elaidic), 13.5; delta10, 22.2; delta11 (vaccenic), 16.0; delta12,
      11.3; delta13-delta14, 12.8; delta15, 2.5; and delta16, 2.2 (total trans 18:1
      acids in the fat supplement: 40.6%). The cis 18:1 isomer profile was (in % of
      total cis-18:1 isomers): delta6-delta8, 2.1; delta9 (oleic), 70.9; delta10, 6.1;
      delta11, 8.3; delta12, 4.0; delta13, 2.8; delta14, 4.6, and delta15, 1.2 (total
      cis-18:1 acids in the fat supplement: 32.6%). Suckling rats from four litters
      were sacrificed at day 17 or 18 after birth, and their stomach content (milk) was
      analyzed. The trans-18:1 isomer profile of milk was (relative proportions, in %
      of total): delta4, 0.3; delta5, 1.1; delta6-delta8, 16.8; delta9, 15.3; delta10,
      22.0; delta11, 16.7; delta12, 11.8; delta13-14, 11.8; delta15, 2.5, and delta16,
      1.9 (total trans 18:1 acids in milk: %). That of cis-18:1 isomers was
      (proportions in % relative to total cis-18:1 isomers): delta6-delta8, 4.7;
      delta9, 72.5; delta10, 4.0; delta11, 8.0; delta12, 7.1; delta13, 1.9; delta14,
      1.0, and delta15, 0.7 (total cis-18:1 acids in milk: %). These results
      demonstrate that all isomeric acids, independent of the geometry and the position
      of the ethylenic bond, are incorporated into milk lipids. With regard to trans
      18:1 isomers, the distribution profile in milk is identical to that in the dams'
      diet, i.e., there is no discrimination against any positional isomer between
      their ingestion and their deposition into milk lipids. As a consequence, this
      study indicates that the trans-18:1 isomer profile of milk reflects that in the
      dams' diet and supports our earlier hypothesis that the profile of trans-18:1
      isomers in milk can be used to deduce the relative contribution of ruminant fats
      and partially hydrogenated oils in the diet to the total intake of trans-18:1
      isomers. On the other hand, the cis-18:1 isomer profile in milk shows significant
      differences when compared to that in the dams' diet. Surprisingly, there are no
      major differences for the cis-delta9 (oleic) and the cis-delta11 (asclepic)
      isomers, which can be synthesized by the mother. However, there seems to be a
      significant positive selectivity for the group cis-delta6-delta8, and for the cis
      delta12 isomer, whereas a negative selectivity occurs for the delta10 and delta13
      to delta15 cis isomers.

PMID- 14733360
TI  - Ligand-binding domain of farnesoid X receptor (FXR) had the highest sensitivity
      and activity among FXR variants in a fluorescence-based assay.
AB  - The farnesoid X receptor (FXR, NR1H4) has been recognized as an attractive
      therapeutic target because it is a nuclear hormone receptor that controls the
      expression level of cholesterol-7alpha-hydroxylase, which in turn regulates bile
      acid production and cholesterol excretion. To compare receptor activity between
      each domain and the full-length protein, human FXR cDNA was cloned from a human
      liver cDNA library. Three human FXR cDNA, designated FXR20, FXR33, and FXR53
      cDNA, were subcloned and ligated into a pET28a expression vector. Each protein
      was expressed in Escherichia coli (BL21) and purified by nickel-nitrilotriacetic
      acid column chromatography. Approximately 5 mg of FXR33 (1-182 amino acids
      deleted from FXR, 37 kDa) and 2 mg of FXR53 (the full-length protein of FXR, 59
      kDa) was purified from 1 L of Luria-Bertani culture, achieving at least 90%
      purity. The coactivator recruitment assay for FXR activation was carried out with
      the three variants of the FXR protein by using dissociation-enhanced lanthanide
      fluoroimmunoassay-europium-N1-labeled anti-His antibody. From an optimized assay,
      a saturated hyperbolic fluorescence signal curve was produced when 250 nM of
      FXR33 and 100 nM of steroid receptor coactivator-1 peptide, a coactivator of FXR
      consisting of 26 amino acids, were used with a concentration dependence on
      chenodeoxycholic acid (from 0 to 200 microM). The ligand-binding domain of FXR
      (FXR33) was the most suitable protein for studying the activation of FXR with a
      fluorescence-based assay, because it showed better structural stability than
      either the full length of FXR (FXR53) or the DNA-binding domain of FXR (FXR20).

PMID- 14733361
TI  - Genes regulated by arachidonic and oleic acids in Raji cells.
AB  - FA are known to modulate immune function in conditions such as arthritis and
      lupus erythematosus. The effects of arachidonic (AA) and oleic acids (OA) on
      function and pleiotropic gene expression of Raji cells were investigated. The
      following parameters were evaluated: cytotoxicity as assessed by loss of membrane
      integrity and DNA fragmentation; proliferation as measured by [14C]thymidine
      incorporation; production of interleukin (IL)-10, interferon (INF)-gamma, and
      tumor necrosis factor (TNF)-alpha; and expression of pleiotropic genes by a
      macroarray technique (83 genes in total). AA was more toxic to Raji cells than
      OA. Both FA promoted an increase in Raji cell proliferation at 75 microM, whereas
      OA at high concentrations (200 microM) decreased proliferation. AA reduced the
      production of IL-10, TNF-alpha, and INF-gamma. On the other hand, OA provoked an
      increase of INF-gamma production but did not affect the production of IL-10 and
      TNF-alpha. The proportions of genes with altered expression were 27% for AA and
      35% for OA. The FA affected the expression of genes clustered as: cytokines,
      signal transduction pathways, transcription factors, cell cycle, defense and
      repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone
      receptors. The most remarkable changes were observed in the genes of signal
      transduction pathways. These results led us to conclude that the effect of these
      FA on B-lymphocytes includes regulation of gene expression. Thus, diets enriched
      with fat containing OA or AA may affect B lymphocyte function in vivo.

PMID- 14733362
TI  - Kinetics of barley FA hydroperoxide lyase are modulated by salts and detergents.
AB  - The cDNA from barley coding FA hydroperoxide lyase (HPL) was cloned. A
      recombinant protein derived from the cDNA was expressed in Escherichia coli as an
      active enzyme. Thus far, there have been no reports on HPL in monocotyledonous
      plants. The recombinant protein was shown to be most active to linolenic acid 13
      hydroperoxide, followed by linoleic acid 13-hydroperoxide. 9-Hydroperoxides of
      the FA could not be substrates for the recombinant HPL. The activity was
      dramatically enhanced in the presence of a detergent and/or a salt in the
      reaction mixture. At the same time, the kinetics of the reaction, including
      inactivation and the Vmax value of the HPL, were also greatly modulated,
      depending on the concentration of a monovalent cation and/or a detergent in the
      reaction mixture. These results suggest that these effectors induced a
      conformational change in barley HPL, resulting in an improvement in substrate
      binding and in enzyme activity.

PMID- 14733363
TI  - Isomers of hexadecenoic and hexadecadienoic acids in Androsace septentrionalis
      (Primulaceae) seed oil.
AB  - Seeds of Androsace septentrionalis of the genus Androsace (tribus Primuleae) from
      the plant family Primulaceae were studied for their oil content and FA
      composition. The seed oil of A. septentrionalis was found to contain two unusual
      FA rarely occurring in plants: 11-cis-hexadecenoic acid (16:1delta11c or 16:1n-5)
      and 9-cis,12-cis-hexadecadienoic acid (16:2delta9c,12c or 16:2n-4). It also
      contained an unusually high amount (21.4%) of 9-cis-hexadecenoic acid
      (palmitoleic acid; 16:1delta9c or 16:1n-7), i.e., at a level higher than that of
      oleic acid, in addition to common FA. Compared with most plant seed oils, at 3.8%
      the level of 18:1delta11c (or 18:1n-7) also was elevated. The nonidentity of the
      Androsace 16:2-acid with the 16:2-acid, which is very typical for Ranunculus
      spp., as well as its identity with the 16:2-acid typically found in
      Asclepiadaceae was established by co-chromatography. The structure and
      composition of the constituent FA of A. septentrionalis were also determined by
      various chromatographic methods (TLC, Ag+-TLC, capillary GLC) and spectroscopic
      methods (IR, GC-MS). The significant deviation of the Androsace FA pattern from
      that of other Primuleae, indicating a separate phylogenetic position of
      Androsace, is discussed.

PMID- 14733364
TI  - Tentative identification and quantification of TAG core aldehydes as
      dinitrophenylhydrazones in autoxidized sunflowerseed oil using reversed-phase
      HPLC with electrospray ionization MS.
AB  - The molecular species of TAG core aldehydes (aldehydes still esterified to parent
      molecules) were detected and quantified in dietary-quality sunflowerseed oil
      autoxidized for 0-18 d at 60 degrees C in the dark. The analyses were performed
      by reversed-phase HPLC with UV (358 nm) absorption or light scattering and
      electrospray ionization-MS (ESI/MS) detection following preparation of the
      dinitrophenylhydrazone derivatives. Aldehyde production, as estimated by UV and
      ESI/MS, increased gradually over the 18-d period following a rapid initial
      destruction of the core aldehydes accumulated during storage of the commercial
      oil at 10 degrees C for 3 mon. The contents of hydroperoxides and hydroperoxide
      core aldehyde combinations were estimated to account for about 5% of total TAG,
      quantified as area in the chromatographic trace, after 18 d of autoxidation as
      estimated by an evaporative light scattering detector (ELSD). The major species
      of core aldehydes were tentatively identified as 9-oxononanoyl (70%)-, 12-oxo
      9,10-epoxydodecenoyl (10%)-, and 13-oxo-9,11-tridecadienoyl (5%)-containing
      acylglycerols, plus smaller amounts of simple and mixed chain-length dialdehydes,
      and hydroxy and epoxy monoaldehyde-containing acylglycerols (15% of total).
      Quantitatively, the core aldehydes made up 2-12 g/kg of oil by UV detection and 2
      9 g/kg of oil by ESI/MS detection, whereas the hydroperoxides measured in the
      unreduced state by HPLC with ELSD were estimated at 200 g/kg after 18 d of
      autoxidation. The major hydroperoxides of sunflowerseed oil were as previously
      identified.

PMID- 14733365
TI  - Effect of ultrasonication and grinding on the determination of lipid class
      content of microalgae harvested on filters.
AB  - To ensure complete lipid extraction of algal samples collected on glass fiber
      filters, one must facilitate the access of extracting solvent to the lipids by
      using ultrasonication, grinding, or a combination of these two methods. This
      study examines the effect of these three treatments, in combination with storage
      time and sampling volumes, on the determination of lipid class composition of the
      diatom Chaetoceros gracilis. The TAG level was significantly influenced by
      treatment in relation to either storage time or sampling volume. FFA and other
      degradation products increased markedly with storage time at the expense of TAG
      and phospholipids (PL). Finally, sampling volume and storage time interacted in
      their effects on TAG and PL contents in an inverse manner.

PMID- 14733366
TI  - Lipase-catalyzed methanolysis of triricinolein in organic solvent to produce
      1,2(2,3)-diricinolein.
AB  - The objective of this study was to find the optimal parameters for lipase
      catalyzed methanolysis of triricinolein to produce 1,2(2,3)-diricinolein. Four
      different immobilized lipases were tested, Candida antarctica type B (CALB),
      Rhizomucor miehei (RML), Pseudomonas cepacia (PCL), and Penicillium roquefortii
      (PRL). n-Hexane and diisopropyl ether (DIPE) were examined as reaction media at
      three different water activities (a(w)), 0.11, 0.53, and 0.97. The consumption of
      triricinolein and the formation of 1,2(2,3)-diricinolein, methyl ricinoleate, and
      ricinoleic acid were followed for up to 48 h. PRL gave the highest yield of
      1,2(2,3)-diricinolein. Moreover, this lipase showed the highest specificity for
      the studied reaction, i.e., high selectivity for the reaction with triricinolein
      but low for 1,2(2,3)-diricinolein. Recoveries of 93 and 88% DAG were obtained
      using PRL in DIPE at a(w) of 0.11 and 0.53, respectively. Further, NMR studies
      showed that a higher purity of the 1,2(2,3)-isomer vs. the 1,3-isomer was
      achieved at higher a(w) (88% at a(w) = 0.53), compared to lower a(w) (71% at a(w)
      = 0.11). The DAG obtained was acylated by the DAG acyltransferase from
      Arabidopsis thaliana. Therefore, this enzymatic product is a useful enzyme
      substrate for lipid biosynthesis. Accordingly, the use of PRL in DIPE at a(w)
      0.53 is considered optimal for the synthesis of 1,2(2,3)-diricinolein from
      triricinolein.

PMID- 14733367
TI  - Occurrence of high levels of tetracosahexaenoic acid in the jellyfish Aurelia sp.
AB  - The FA composition of the pelagic jellyfish Aurelia sp. collected from off-shore
      Western Australia waters was determined by capillary GC and GC-MS, with
      confirmation of PUFA structure performed by analysis of 4,4-dimethyloxazoline
      derivatives. PUFA constituted 47.6% of the total FA, with the essential PUFA
      eicosapentaenoic acid (EPA), arachidonic acid, and DHA accounting for 34%. Of
      particular interest, the unusual very long chain PUFA 6,9,12,15,18,21
      tetracosahexaenoic acid (THA, 24:6n-3) was present at 9.3%, and the rarely
      reported 6,9,12,15,18-tetracosapentaenoic acid (24:5n-6) also was detected at
      0.8%. To our knowledge, this represents the first report of THA as a major PUFA
      in a pelagic marine organism.

PMID- 14733368
TI  - A summer in public health research.

PMID- 14733369
TI  - Wisconsin Medical Society Foundation purpose supports medical and health
      education.

PMID- 14733370
TI  - Workforce shortage mandates change... now.

PMID- 14733371
TI  - Health care worker shortage: pervasive and long-term.

PMID- 14733372
TI  - Physician shortage: misdiagnosis & prognosis.

PMID- 14733373
TI  - Wisconsin can prepare and support rural physicians.
AB  - The Institute of Medicine of the National Academies in its November 2002 report,
      Fostering Rapid Advances in Health Care: Learning from System Demonstrations,
      gives the best vision for American health care I have yet come across. "The
      health care system of the 21st century should maximize the health and functioning
      of both individual patients and communities. To accomplish this goal, the system
      should balance and integrate needs for personal health care with broader
      community-wide initiatives that target the entire population. The health care
      system must have well-defined processes for making the best use of limited
      resources." It is our job in Wisconsin to assure that we have "well-defined
      processes for making the best use of limited resources" for preparing and
      supporting physicians in rural communities.

PMID- 14733374
TI  - Progress in reducing mortality among Wisconsin residents, 1980-2000: rates
      decline, but black-white disparities increase.
AB  - PURPOSE: To assess progress towards 2 overarching public health goals-
      improvement in length of life and reducing health disparities. METHODS: Age
      specific mortality rates in Wisconsin from 1980 to 2000 were obtained from the US
      Centers for Disease Control and Prevention WONDER database. Rates for each age
      group were gathered for the entire Wisconsin population and for black and white
      subgroups. Trends in mortality rates were plotted, change in mortality rates was
      estimated, and the number of "lives saved" annually from 1980-1984 to 1996-2000
      was calculated. In addition, black vs white rate ratios were calculated at both
      the beginning and the end of the time period to determine trends in black-white
      mortality disparities. RESULTS: Mortality is decreasing in Wisconsin in every age
      group. The largest relative improvements in mortality rates occurred among
      infants <1 year (-30%), children 1-14 years (-27%), and adults 45-64 years (
      23%). Comparatively little progress was seen among adults 25-44 years (-5%) and
      those 85 years and older (-0.5%). Black/white disparities increased in every age
      group. During 1996-2000, approximately 5000 fewer deaths occurred each year than
      expected based on mortality rates from 1980-1984. CONCLUSION: Despite progress
      towards increasing length of life, progress towards eliminating disparities was
      not seen over the 1980 to 2000 time period.

PMID- 14733375
TI  - Monitoring infant mortality trends in Wisconsin, 1980 to 1999.
AB  - Using data from the National Center for Health Statistics, this paper analyzes
      the trends in infant, neonatal, and postneonatal mortality in Wisconsin between
      1980 and 1999. The main causes of infant death are also examined. Results
      indicate that whites have consistently experienced a steady decline in infant
      mortality, from 9.2 per 1000 live births in 1980-1984 to 6.0 in 1995-1999. The
      rate for black infants was 19.4 in 1980-1984, fluctuated during this period, and
      was 17.8 in 1995-1999. Overall, infant mortality rates in Wisconsin continue to
      decrease, but the disparity between blacks and whites remains large and continues
      to increase. Death rates due to prematurity have increased by almost 82% between
      1980 and 1999, while deaths from congenital anomalies have declined. Wisconsin
      white infant mortality rates are decreasing at rates in line with the goals for
      Healthy People 2010, but Wisconsin black infant mortality rates must decrease
      significantly in order to meet the national and state goals.

PMID- 14733376
TI  - Health priorities in Wisconsin: a case for tracking childhood mortality.
AB  - OBJECTIVE: To assess trends in mortality among children ages 1-14 in Wisconsin
      over the last 2 decades and prompt policymakers to include annual monitoring of
      childhood mortality in the state Health Plan for 2010. METHODS: Data for all
      cause and cause-specific (intentional-, unintentional-, non-injury related)
      mortality for 1980-1999 were obtained from WONDER, the Centers for Disease
      Control and Prevention's mortality database, and stratified by black/white race
      and gender. Trends were assessed using the 5-year moving average method and
      projected to 2010 to estimate future mortality. RESULTS: Childhood mortality
      rates in Wisconsin decreased 26% from 1980-1999 to 23.7/100,000 population,
      representing 87 lives saved annually. Throughout this period, Wisconsin's
      mortality rate was lower than the national average; however, disparities have
      increased. Boys and blacks experienced the highest death rates and the greatest
      increases in rates from homicide and suicide. If trends continue, Wisconsin is
      predicted to have the same overall rate as the United States in 2010.
      CONCLUSIONS: Wisconsin has experienced slower rates of decline in childhood
      mortality than the United States over the past 20 years, due, in part, to
      increasing disparities by race and gender. To halt this phenomenon, policymakers
      should include annual monitoring of childhood mortality rates in the state health
      plan and support appropriate interventions for children at risk.

PMID- 14733377
TI  - Reducing mortality in adolescents and young adults in Wisconsin: are we making
      progress?
AB  - OBJECTIVE: Has there been progress in the reduction of adolescent and young adult
      mortality in Wisconsin over the last 20 years? This paper addresses this question
      by examining the mortality trends--and disparities by race and gender--of
      adolescents and young adults in Wisconsin, ages 15-24. METHODS: Mortality data
      for blacks and whites from 1980-1999 for Wisconsin and the United States were
      accessed from the Centers for Disease Control and Prevention's Web-based database
      system CDC WONDER. Mean death rates were calculated for the 5-year spans 1980
      1984 and 1995-1999. A Poisson model for rates was used to summarize the death
      rates and perform predictions. RESULTS: Wisconsin and the United States have
      reduced mortality in the age group 15-24 by about 17% and 16%, respectively,
      between 1980-1984 and 1995-1999. In spite of this overall progress, significant
      disparities still exist between white and black older adolescents and young
      adults. When compared to 1980-1984, Wisconsin mortality rates for 1995-1999 were
      24% lower among whites, but 73% higher among blacks. Disparities still exist when
      rates are analyzed by the leading causes of deaths. Deaths due to motor vehicle
      injuries have decreased for whites by about 31% compared to an increase of 19%
      for blacks. CONCLUSIONS: Wisconsin has made progress in reducing death rates in
      adolescents and young adults, especially in fatal motor vehicle injuries.
      However, significant disparities still exist between whites and blacks, males and
      females, and leading causes of deaths. Wisconsin should work to reduce the
      mortality rate in adolescents and young adults and to eliminate disparities by
      2010.

PMID- 14733378
TI  - Has there been progress in reducing mortality among Wisconsin adults ages 25 to
      44?
AB  - Wisconsin residents age 25-44 years represent an important life stage and a
      relatively large portion of the Wisconsin population. Focusing on the most common
      causes of death among Wisconsin adults 25-44 years old, we assess progress in
      reducing mortality, describe disparities between subgroups of this age group, and
      identify areas for improvement. Mortality trends and leading causes of death were
      examined from 1980-1999 by querying the Centers for Disease Control and
      Prevention's WONDER database using the methods established by the National Vital
      Statistics System. Mortality rates in Wisconsin declined slightly (5%) during
      this time, and are consistently lower than the national rates. Mortality due to
      unintentional injury, cancer, and coronary heart disease declined in this age
      group. However, this decline was in contrast to increases in mortality due to
      suicide, homicide, and HIV--all preventable causes of death. Finally, disparities
      in mortality rates increased between black and white Wisconsin residents. In
      order to make progress in this age group, public health efforts need to focus on
      effective strategies to prevent HIV and violence.

PMID- 14733379
TI  - A decline in adult mortality, ages 45-64, in Wisconsin over the last 20 years: is
      it enough?
AB  - INTRODUCTION: Decreasing mortality is an important objective of health
      improvement. We examined the progress in reducing overall mortality in Wisconsin
      over the last 2 decades in the age group spanning 45-64 years. Goals for reducing
      mortality and disparities in mortality by 2010 were addressed. METHODS: We
      examined trends in all cause mortality for Wisconsin from 1980-1999 for ages 45
      64. Mortality data was also examined by subgroups (race and gender) and cause.
      Mortality data was abstracted from Centers for Disease Control and Prevention's
      WONDER. RESULTS: From 1980-99, adults aged 45-64 experienced a 22% decline in
      mortality and, consequently, over 1720 lives were "saved" annually in Wisconsin
      in this age group between 1995-1999. Mortality in black men and women declined 8%
      and 10% respectively in this interval as compared to 27% for white males and 19%
      for white females (P<0.05 for all groups for temporal change in death rates).
      Significant declines in cardiovascular and cancer mortality were achieved. Deaths
      from injuries increased slightly. The black to white mortality ratio is projected
      to increase by 2010. CONCLUSIONS: Wisconsin has done well in reducing overall
      mortality in persons 45-64 years of age over the last 2 decades. Future
      challenges include reducing health disparities between blacks and whites.

PMID- 14733380
TI  - Progress in reducing mortality among persons 65 to 74 years of age in Wisconsin.
AB  - OBJECTIVES: To assess progress in reducing mortality between 1980 and 1999 among
      Wisconsin residents aged 65-74, to identify disparities, and to propose future
      goals. METHODS: Mortality rates for 1980-1984 were compared to those from 1995
      1999 using data obtained from the Centers for Disease Control and Prevention's
      WONDER database. Percent change in rates were calculated and projected to 2010,
      and annual numbers of lives saved were estimated. RESULTS: The mortality rate for
      persons aged 65-74 has decreased 12.4%-17.5% in men and 6.3% in women. However,
      no reductions were observed for blacks. An estimated 1325 fewer deaths occur each
      year, with white men accounting for >80% of these savings. Mortality rates
      decreased for heart disease (-38%) and stroke (-26%), but increased for cancer
      (+6%). CONCLUSIONS: Significant progress has been made in reducing mortality
      among Wisconsin residents aged 65-74, but not among blacks. Most of the progress
      is due to decreased deaths from heart disease and stroke, particularly for white
      men.

PMID- 14733381
TI  - Pesticides and your children: a randomized controlled evaluation of a pamphlet.
AB  - BACKGROUND: Maternal and pediatric residential pesticide exposure has been
      identified as a risk factor for birth defects, pediatric cancers, and
      neurological damage, and it may play a role in other disease processes.
      OBJECTIVE: To examine whether the use of a pamphlet with a brief educational
      message in a clinic setting would increase the knowledge and/or change the
      attitudes of pregnant women and mothers about pesticide use and alternatives, as
      well as promote pesticide safety. METHODS: A group of 103 women currently
      pregnant and/or with children less than 6 years of age were recruited at 2
      Special Supplemental Nutrition Program for Women, Infants and Children (WIC)
      clinics for the study. Participants were given a 16-question true/false oral
      survey testing their baseline knowledge about pesticide safety and safer
      alternatives to pesticide use. Participants were then randomly assigned to a
      control group or to the intervention group, which received the pamphlet and a 2
      minute scripted overview of its contents. Approximately 2 to 3 weeks later, all
      participants received a follow-up telephone call by a researcher blinded to the
      original group assignment, and the original survey questions were repeated.
      RESULTS: Follow-up assessments were completed for 73 (71%) of the participants.
      The mean improvement in correct responses on the follow-up survey was +0.39 for
      the control group and +3.1 for the intervention group (P<.001). Item analysis
      revealed that the intervention produced a significantly higher number of correct
      answers to 9 of the 16 survey questions. Providing mothers and pregnant women
      CONCLUSIONS: Providing mothers and pregnant women with a pamphlet and a brief
      message about pesticide safety and safer alternatives to pesticides in a clinic
      setting may be effective in improving knowledge and beliefs about pesticides.

PMID- 14733382
TI  - Impending physician shortage needs decisive remediation.

PMID- 14733383
TI  - Prepare your children for their financial future.

PMID- 14733384
TI  - Improving care in physician offices.

PMID- 14733385
TI  - Fate of phosphorus from biological aerobic treatment of pig slurry. By-products
      characterization and recovery.
AB  - The fate of phosphorus distribution in the products obtained from biological
      aerobic treatment of pig slurry, e.g. separated solids, liquid effluent and
      sludge, was monitored in three different farm-scale units. Samples of raw slurry,
      solid products, aerated slurry, liquid effluent and sludge were characterised and
      analysed for their concentration in total phosphorus, nitrogen content and heavy
      metals (Cu and Zn). At each treatment stage, nitrogen, phosphorus and heavy
      metals mass balance between input and output was established. Moreover, liquid
      products were characterised and analysed both for their total and dissolved ortho
      phosphate content. Separated solids, sludge and liquid effluent represented 5%,
      15-40% and 75-83% of the mass of the raw slurry, respectively. A mechanical
      separation step prior to aeration allowed the export of 25-30% of total
      phosphorus for further use as organic fertiliser. A large amount of total
      phosphorus (e.g. 60-70%) was located in sludge while phosphorus remaining in
      liquid effluent was about 15-25%. Raw slurry separation and sufficient aeration
      allowed phosphorus to concentrate in the sludge. Insufficient aeration resulted
      in the release of phosphorus as dissolved ortho-phosphate within the liquid
      effluent. Finally, relevance of the agronomic use of the products was discussed
      and improvements of biological aerobic treatment to enhance phosphorus removal
      and/or recovery were considered.

PMID- 14733386
TI  - Effect of carbon to nitrogen ratio on the physical and chemical properties of
      activated sludge.
AB  - The effect of carbon to nitrogen ratio (C/N) of the feed on the physical and
      surface chemical properties of activated sludge is investigated. Semi-continuous
      reactors with 2 liters volume were operated at a mean cell residence time of 8
      days. These mixed culture reactors were operated at 3 different carbon to
      nitrogen ratio. The operation of conventional activated sludge plants treating
      municipal wastewater is represented with reactors having a C/N ratio of 21 (in
      terms of the ratio of COD to TKN). Carbon and nitrogen limited activated sludge
      systems are represented by reactors with a C/N ratio of 9 and 43, respectively.
      The results show that C/N ratio has a profound effect on the ultimate physical
      and surface chemical properties of activated sludge. Both the steady state
      microorganism concentration and the amount of microbial extracellular polymers
      produced increase with increasing C/N ratio. The sludge becomes much harder to
      dewater and settle and it becomes more viscous as the C/N ratio increases. A
      decrease in surface hydrophobicity and an increase in surface charge of the
      sludge accompany these physical changes.

PMID- 14733387
TI  - Chlorination for degrading saxitoxins (paralytic shellfish poisons) in water.
AB  - Chlorination was investigated as a treatment option for degrading and thus
      removing saxitoxins (paralytic shellfish poisons, PSPs) produced by cyanobacteria
      (blue-green algae) from water. It was found to be effective with the order of
      ease of degradation of the saxitoxins being GTX5 (B1) approximately dcSTX > STX >
      GTX3 approximately C2 > C1 > GTX2. However the effectiveness of chlorine was pH
      dependent. Degradation as a function of pH was not linear with the degree of
      degradation increasing rapidly at around pH 7.5. At pH 9 > 90% removal was
      possible provided a residual of 0.5 mg l(-1) free chlorine was present after 30
      min contact time. The more effective degradation at higher pH was unexpected as
      chlorine is known to be a weaker oxidant under these conditions. The more
      effective degradation, then, must be due to the toxins, which are ionisable
      molecules, being present in a form at higher pH which is more susceptible to
      oxidation. The feasibility of using chlorine to remove saxitoxins during water
      treatment will therefore depend strongly on the pH of the water being
      chlorinated. Degradation may be improved by pH adjustment but may not be a
      practical solution. Although saxitoxins were degraded in that the parent
      compounds were not detected by chemical analysis, there is no indication as to
      the nature of the degradation products. However, acute toxicity as determined by
      the mouse bioassay was eliminated.

PMID- 14733388
TI  - The distribution and speciation of antimony in river water, sediment and biota in
      Yodo River, Japan.
AB  - In 1993, the Japanese government set the guideline concentration of 2 microg l(
      1) for antimony in natural water and drinking water as an item for precautionary
      monitoring in consideration of its chronic toxicity, however in 1999 the
      guideline value was tentatively canceled to examine the health risk of antimony
      through the accumulation of more information and data for detailed risk
      assessment. In this study, the distribution of antimony in the river water
      environment including water, sediment, aquatic plants and fishes was surveyed in
      the Yodo River basin. The characteristics of antimony distribution between river
      water and sediment were determined by the batch sorption experiments, focusing on
      the difference in oxidation state. This study suggests that biota in the Yodo
      River basin have antimony at concentrated levels. Some of the sewage treatment
      plants seemed to influence the concentration of antimony in river water. It was
      shown that the pentavalent antimony is dominant in river water and especially
      paramount downstream of the sewage treatment plants, though the trivalent
      antimony is dominant in industrial use. According to the sorption experiments of
      antimony on river sediment, the trivalent antimony is sorbed faster and more in
      partition than the pentavalent antimony.

PMID- 14733389
TI  - [Coagulation-flocculation performances for cuttlefish effluents treatment].
AB  - Coagulation-flocculation of the colloids particles present in the cuttlefish
      effluents was investigated using a coagulation step with aluminium sulphate (SA),
      followed by a flocculation step with starch, SiO2 or MgO and then poly dimethyl
      ammonium chloride (PDMAC), in order to reduce the turbidity and chemical oxygen
      demand (COD). Kinetic aspects, adsorption equilibrium, pH and conductivity were
      studied in order to determine the optimum coagulation conditions and SA
      quantities. The addition of organic polymer as a flocculant agent gave a better
      performance than the use of salt alone with a reduction of 50% of the SA
      consumption. Polymer molecular weight of PDMAC and charge density of starch have
      been also investigated. The best result, which is 90% of removal rate in chemical
      oxygen demand (COD) and a turbidity value of 7 NTU was obtained with the
      combination using 165.5 mg l(-1) of aluminium sulphate, 750 mg l(-1) of MgO and
      35 mg l(-1) of PDMAC 400000.

PMID- 14733390
TI  - Rare earth elements removal by microbial biosorption: a review.
AB  - This paper reviews published work on the sorption of rare earth elements by
      microbial biomass. In a first part, the biosorption capacities and the various
      experimental conditions performed in batch reactor experiments are compared.
      Secondly, sorption modelling generally used in biosorption studies are described.
      Thirdly, the microbial cell wall characteristics of the metallic ion binding
      sites are considered. From these observations it seems that the important
      functional groups for metallic ion fixation are the carboxyl and the phosphate
      moieties. Moreover, the competing effect of various ions like aluminium, iron,
      glutamate, sulphate etc. is described. Finally, some adsorption results of the
      rare earth elements in dynamic reactors are presented.

PMID- 14733391
TI  - A new approach for estimating the labile aluminium fraction in soil solutions,
      through batch experiments, using cationic (Amberlite IR 120) or non ionic
      (Amberlite XAD 2) resins.
AB  - Aluminium fractionation was tested on two types of resin. The first approach was
      based on the selective sorption of cationic forms on a strong cation exchange
      resin (Amberlite IR 120) which is commonly used. Using a defined contact time (1
      hour) between solution and resin (batch technique) it was possible to obtain
      separation between different aluminium species. The second approach was based on
      the sorption of organic matter, especially complexes between organic matter and
      aluminium, onto a non ionic resin (Amberlite XAD 2), batch reactors containing
      the solution and the resin were stirred for 16 hours. Some tests were carried out
      to compare the different techniques using samples containing various complexing
      molecules (salicylic acid and purified commercial humic acid). Aluminium
      fractionation was then carried out on different soil solutions with the two
      different types of resin. Horizons A and S from acid brown soil under chestnut
      and Douglas fir were used in order to compare the influence of the type and the
      content of organic matter on the released aluminium forms. It appears that A
      layers release more total aluminium than the S ones but only a small part is in
      cationic forms. The S layer presents Al essentially under reactive cationic
      forms.

PMID- 14733392
TI  - Enhanced wet air oxidation of sediment contaminated with PCBs.
AB  - Wet air oxidation (WAO) is investigated as a method of treating river sediments
      contaminated with polychlorinated biphenyls (PCBs). Aqueous slurries containing
      2.5% (w/w) sediment were oxidized with oxygen in a one liter, high-pressure,
      batch reactor at temperatures up to 250 degrees C. Concentrations of PCBs
      adsorbed on the sediment and reactor surfaces and dissolved in the water and gas
      phases after oxidation were determined by high-resolution gas chromatography.
      Results indicate that no significant wet oxidation of PCBs in sediment slurries
      occurs for temperatures at or below 250 degrees C. However, during reactor heat
      up, significant degradation of PCBs occurred at high temperature regions near the
      reactor wall even when bulk fluid temperature was quite low. A variety of
      amendments were tested to determine their effect on PCB oxidation. These
      amendments included hydrogen peroxide, a readily degraded organic compound
      (phenol), and homogeneous copper catalyst. Only hydrogen peroxide addition
      resulted in a significant degradation of PCBs. The addition of phenol did not
      result in enhanced degradation of PCBs through kinetic coupling as has been
      observed for other recalcitrant organic compounds.

PMID- 14733393
TI  - Literature review on textile wastewater characterisation.
AB  - In the textile industry, many different processes are used and almost all of them
      generate wastewater. The effluents resulting from these processes differ greatly
      in composition, due to differences in processes, used fabrics and machinery.
      Textile wastewater is usually treated as a mixed stream. For water and chemicals
      reuse purposes however, it is preferable to keep process streams apart and treat
      them separately. Characterisation of textile industry effluents is of great
      importance for the separate treatment of process streams. This literature review
      provides an overview of what is known about the wastewater of the separate
      processes, and the methods used for characterisation of these streams.

PMID- 14733394
TI  - [Bioleaching kinetic of a pyrite mining residue using organic wastes as culture
      media for Acidithiobacillus ferrooxidans].
AB  - In this study, the results of the leaching of metal sulphide concentrate using
      organic wastes as culture media for Acidithiobacillus ferrooxidans are
      summarized. These results indicate that the liquid fraction of municipal sewage
      sludge, paper mill sludge and pig manure, containing 10% (w v(-1)) pulp density
      of a pyritic mine waste concentrate can support the growth of the leaching
      bacteria and allow metal solubilization. The inhibition by dissolved organic
      carbon (DOC) appeared when the concentration in pig manure liquid fraction and
      sewage sludge filtrate is higher than 180 mg l(-1) and 500 mg l(-1),
      respectively. However, increase in organic concentration up to 650 mg l(-1) using
      paper mill sludge supernatant had no inhibitory effect on the bacterial growth.
      An important decrease of the DOC has been measured during all bioleaching tests.
      The organic matter was probably consumed by heterotrophic microorganisms
      activity. The growth rate of the iron-oxidizing bacteria varied from 0.05 to 0.07
      h(-1). The dissolution of pyrite (FeS2) in organic waste media led to a yield of
      Fe solubilization of about 35%. Copper and zinc were also solubilized during the
      bioleaching tests. The yields of Cu and Zn solubilization ranged from 12 to 24%.

PMID- 14733395
TI  - Cyclone as a precleaner to ESP--a need for Indian coal based thermal power
      plants.
AB  - Almost all coal based thermal power plants (CTPP) in India use electrostatic
      precipitator (ESP) for reduction of particulate matter (PM) in flue gas generated
      due to the combustion of Indian coal. This coal is characterized by high ash
      content, low calorific value and low sulfur content resulting in the generation
      of a very large amount of highly electrically-resistive fly-ash; thereby
      requiring a very large size ESP to minimize the fly-ash emissions. However, the
      flue-gas particle size distribution analysis showed that 60% of the particles are
      above 15 microm size, which can be conveniently removed using a low-cost inertial
      separator such as a cyclone separator. It is proposed that a cyclone be used, as
      a pre-cleaner to ESP so that the large size fraction of fly-ash can be removed in
      the pre-cleaning and the remaining flue-gas entering the ESP will then contain
      only small size particles with low dust loading, thereby requiring a small ESP,
      and improving overall efficiency of dust removal. A low efficiency (65%), high
      throughput cyclone is considered for pre-cleaning flue gas and the ESP is
      designed for removal of the remaining 35% fly-ash from the flue gas. It is
      observed that with 100% dust load, the ESP requires six fields per pass, whereas
      with cyclone as a pre-cleaner, it requires only five fields per pass. Introducing
      cyclone into the flue gas path results in additional head loss, which needs to be
      overcome by providing additional power to induced draft (ID) fan. The permissible
      head loss due to the cyclone is estimated by comparing the power requirement in
      the bag filter control unit and cyclone-ESP combined unit. It is estimated that a
      head loss of 10 cm of water can be permitted across the cyclone so as to design
      the same for 65% efficiency.

PMID- 14733396
TI  - Anaerobic digestion of dairy wastewater by inverse fluidization: the inverse
      fluidized bed and the inverse turbulent bed reactors.
AB  - This paper describes the application of the inverse fluidization technology to
      the anaerobic digestion of dairy wastewater. Two reactors were investigated: the
      inverse fluidized bed reactor and the inverse turbulent reactor. In these
      reactors, a granular floating solid is expanded by a down-flow current of
      effluent or an up-flow current of gas, respectively. The carrier particles
      (Extendospheres) were chosen for their large specific surface area (20,000 m2m(
      3)) and their low energy requirements for fluidization (gas velocity of 1.5 mm s(
      1), 5.4 m h(-1)). Organic load was increased stepwise by reducing hydraulic
      retention time from more than 60 days to 3 days, while maintaining constant the
      feed COD concentration. Both reactors achieved more than 90% of COD removal, at
      an organic loading rate of 10-12 kgCOD m(-3) d(-1), respectively. The
      performances observed were similar or even higher than that of other previously
      tested fluidized bed technologies treating the same wastewater. It was found that
      the main advantages of this system are: low energy requirement, because of the
      low fluidization velocities required; there is no need of a settling device,
      because solids accumulate at the bottom of the reactor, so they can be easily
      drawn out and particles with high-biomass content can be easily recovered. Lipid
      phosphate concentration has been revealed as a good method for biomass estimation
      in biofilms since it only includes living biomass.

PMID- 14733397
TI  - Application of ferric sludge to immobilize leachable mercury in soils and
      concrete.
AB  - A Hg-contaminated site in B.C. Province, Canada was caused by the previous
      operation of Hg-cell in chlor-alkali process for over 25 years. The soils and
      groundwater at the site are highly contaminated with mercury. An analysis of
      groundwater at the site has shown that most of the mercury is bonded with humic
      and fulvic acids (HFA) in colloidal form. The Hg-HFA colloids can be completely
      removed from the groundwater with ferric chloride treatment under optimized
      process conditions to form ferric sludge (FS), which is rendered non-leachable by
      standard TCLP (Toxicity Characteristic Leaching Procedure) test. The effluent
      discharged from a clarifier has achieved mercury levels of < 0.5 microkg l(-1).
      The studies of mercury adsorption characteristics of FS show it has low mercury
      leachability by TCLP, and great mercury adsorption capability. This feature is
      the basis for the application of FS to immobilization of leachable Hg
      contaminants in solid wastes. Full-scale stabilization tests of Hg-contaminated
      soil have been carried out, and the time-based stability of the treated soil has
      been monitored by TCLP over a period of 60 days. All the results have shown a
      small variation in TCLP mercury levels within a range of 10-40 microg l(-1).
      Based on these results and with the approval of the B.C. Ministry of the
      Environment, 1850 tons of Hg-contaminated soils and 260 tons of Hg-contaminated
      concrete fines have been treated, stabilized with FS, and disposed in a non
      hazardous waste disposal site.

PMID- 14733398
TI  - Evidence-based medicine versus evidence-based policy: family medicine in the
      frontline.

PMID- 14733399
TI  - New European guidelines on cardiovascular disease prevention in clinical
      practice.

PMID- 14733400
TI  - The cost and cost-effectiveness of PPIs--GP perspectives and responses to a
      prescribing dilemma and their implications for the development of patient-centred
      healthcare.
AB  - BACKGROUND: Evidence-based medicine (EBM) has stimulated a proliferation of
      clinical guidelines and prescribing protocols which aim to increase quality and
      improve equity of healthcare through the standardisation of treatment and access
      to resources. The containment of rising prescribing costs is a major concern of
      European healthcare systems, which has led to a more overt rationing of
      resources. However, prescribing guidelines and cost-containment strategies reduce
      the capacity of health professionals to involve patients in discussion and choice
      of treatment and consequently work against the objectives of patient-centred
      medicine (PCM), which are a priority of current UK healthcare policy. Little is
      known about the impact of prescribing guidelines or cost-containment strategies
      on the practice of medicine in the primary care sector, their effect on relations
      between doctors and patients, and the ways in which laymen and professionals
      evaluate and respond to strategies for more 'rational' prescribing. AIM: This
      paper considers the responses of general practitioners (GPs) in the UK to the
      conflicting commitments of meeting the clinical needs of individual patients and
      dealing with the situational constraints of the consultation, while also
      achieving a reduction in prescribing rates (and costs) of proton pump inhibitors
      (PPIs) in the treatment of gastric disorders. METHOD: Qualitative interview-based
      research involving 26 GPs. RESULTS: Most doctors considered that they were making
      an effort to achieve a reduction in PPI prescribing, and none regarded his
      current prescribing of PPIs to be inappropriate. However, the raised prescribing
      thresholds for PPIs, which were a consequence of applying a cost-containment
      policy, conflicted with the GPs' stated commitment to provide the best and most
      appropriate treatment for individual patients. In addition, the aim to reduce PPI
      prescribing was often subverted by the situational constraints of the
      consultation, and doctors' desire to protect their relationship with patients.
      CONCLUSION: An outcome of the conflicting pressures to which the doctors were
      subject in their efforts to meet clinical need while also reducing the cost of
      PPIs was the reinforcement of widespread assumptions and negative patient
      stereotypes relating to a 'mythology' of PPI prescribing. The prevalence of such
      stereotypes inhibits the reflexivity in medical practice, which is required for
      doctors to perceive and respond more constructively to patient perspectives of
      illness and treatment. Such typifications also function to justify the rationing
      of treatment on the basis of inappropriate judgements about the deservingness or
      moral worth of patients. The study illustrates the adverse impact on medical
      practice of GPs' responses to the competing pressures of meeting patient needs
      while complying with prescribing incentives and guidelines. It highlights the
      incompatibility of different policies relating to cost containment and patient
      centred medicine and may help to explain the systematic inertia which appears to
      have hindered the development of genuinely patient-centred medicine over the last
      few decades.

PMID- 14733401
TI  - Promoting behaviour change in patients with coronary heart disease--a consensus
      study in two countries with different healthcare systems.
AB  - BACKGROUND: Secondary prevention is an effective strategy for reducing coronary
      heart disease morbidity and mortality. Secondary prevention in primary care has
      been shown to be suboptimal. Evidence on approaches to behaviour change, suitable
      for implementation in primary care, is needed. OBJECTIVE: To identify approaches
      to behaviour change in patients with coronary heart disease that are relevant to
      primary care and compare the views of health professionals in two different
      healthcare systems (United Kingdom and the Republic of Ireland). METHODS: Two
      nominal groups were conducted in Northeast Scotland and the West of Ireland with
      expert panels representing core and extended primary care teams. Participants
      were asked to generate ideas, rank them, and then discuss areas of disagreement
      before a second round of ranking. RESULTS: In both groups, there was good
      consensus on items relating to individual patient assessment (including
      motivation and understanding), addressing the practitioner's willingness to
      change, using established principles of behaviour change, and having adequate
      resources, staff and time. Priorities were, however, different. Emphasis on items
      relating to resources, staff and organisation was particularly strong in the
      Irish group; there was more emphasis on approaches to behaviour change in the
      Scottish group. CONCLUSIONS: When attempting to promote behaviour change and
      secondary prevention, there are different priorities in different healthcare
      systems. These should be taken into account in the design of any intervention.

PMID- 14733402
TI  - General practitioner contacts with older residents in nursing and residential
      homes.

PMID- 14733403
TI  - Asthmatic children's inhalation techniques in general practice.

PMID- 14733404
TI  - Accuracy of electronic patient record registration in chronic psychosis--a case
      study of a group practice.

PMID- 14733405
TI  - Preventive thinking--a contradiction to individualised doctoring.

PMID- 14733406
TI  - Transplantation of kidneys from HCV-positive donors: a safe strategy?
AB  - Hepatitis C Virus (HCV) infection is the most important cause of liver disease
      after renal transplantation (RT). The impact of HCV on patient and graft survival
      after RT remains controversial; however, the great majority of studies with large
      size and adequate follow-up have shown the detrimental impact of HCV on long-term
      patient and graft survival after RT. The use of kidneys from anti-HCV positive
      donors could help decrease the continuing disparity between the number of
      patients on the transplant waiting list and the number of patients receiving a
      transplant each year. Single-center experiences have suggested transplanting
      kidneys from anti-HCV positive donors only in anti-HCV positive dialysis
      patients. Such practice has not demonstrated any adverse effect on the short-term
      patient survival; the waiting times for RT were shortened. A better alternative
      seems to be a policy of transplanting kidneys from anti-HCV positive donors only
      in HCV RNA positive recipients. This requires HCV RNA testing of all anti-HCV
      positive dialysis patients awaiting RT. Matching donors and recipients for HCV
      genotype has been suggested; however, the assessment of donor HCV genotype is
      currently hampered by time constraints. Recent evidence based on large data base
      demonstrated that RT recipients of HCV-positive donors are at independent
      increased risk of mortality; unadjusted 3-year patient survival was 85% versus
      93% (P=0.01) in all recipients of donor HCV-positive and HCV-negative kidneys,
      respectively. This was observed in all recipient subgroups including elderly and
      HCV-positive recipients. In the near future, rapid nucleic acid testing (NAT) of
      donors and recipients will allow the assessment of the HCV viremic status in
      order to maximize organ use. With appropriate informed consent, use of a renal
      graft from an HCV positive donor may be offered to an HCV infected recipient.
      Additional studies are needed to clarify the link between donor HCV-positive
      kidneys and patient mortality.

PMID- 14733407
TI  - Post-transplant diabetes mellitus.
AB  - Post-transplant diabetes mellitus (PTDM) is a frequent and serious complication
      after kidney transplantation. Its ethiopathogenesis is multifactorial and
      includes the immunosuppressive regimen, the ethnicity, older age and the body
      mass index. Among these, calcineurine inhibitor and steroid use seems to have
      outstanding relevance. Both patient and graft survival is significantly reduced
      in recipients affected by PTDM. The main clinical aspects of transplant
      recipients with PTDM are patient and graft survival rate, infections,
      cardiovascular complications and late complications of diabetes that include
      nephropathy, neuropathy, retinopathy, micro-macroangiopathy and bone disease. The
      main stages of PTDM prophylaxis and treatment are: to identify patients at risk
      pre-transplantation; to control modifiable risk factors post-transplantation; to
      control hypertension and lipid profiles and a strict metabolic control. Insulin
      treatment is indicated mainly in thin patients and oral hypoglycemic agents
      should be reserved for overweight patients. Transplant centers are currently
      accepting higher risk candidates for post-transplant complications; therefore,
      attention needs to shift to the prevention and the control of complications, such
      as PTDM, because they can lead to a poor quality of life and an increased
      mortality in patients with functioning grafts.

PMID- 14733408
TI  - Myocardial texture characterization in uremics by ultrasonic videodensitometric
      analysis: a review.
AB  - Many studies have demonstrated that left ventricular hypertrophy is the most
      frequent cardiac alteration in patients on chronic hemodialysis. Autopsy studies
      have shown that hypertrophic hearts of uremic patients have peculiar
      characteristics, namely deposition of calcium salts, intermyocytic fibrosis,
      sometimes amyloid. None of the parameters obtainable from conventional
      echocardiografic images provides information on myocardial tissue structure.
      Analysis of "texture" originated as analysis of images sent by satellites for
      military or agricultural purposes and subsequently was applied to medicine for
      studying various organs like mainly and widely heart. Videodensitometry is a
      method for in vivo analysis of myocardial structure using computer-assisted
      quantitative assessment of grey levels of conventional echocardiographic images.
      In dialysis patients quantitative ultrasonic analysis of myocardial texture
      appears a promising technique for an observer-independent assessment of
      myocardial tissue characteristics. Although it may be hampered by many
      potentially confounding factors, quantitative echocardiography may offer useful
      parameters for the follow-up of myocardial structural changes in chronic uremia.
      Further studies are ongoing to completely understand the prognostic significance
      of myocardial ultrasonic textural alterations in dialysis population.

PMID- 14733409
TI  - Possible involvement of TNF-alpha in left ventricular remodeling in hemodialysis
      patients.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha causes hypertrophic as well as
      negative inotropic effects on cardiac myocytes. Circulating TNF-alpha levels are
      reported to be elevated in end-stage renal disease (ESRD) patients undergoing
      maintenance hemodialysis (HD). We investigated whether increased circulating TNF
      alpha is associated with left ventricular remodeling against pressure and/or
      volume overload in HD patients with or without diabetes mellitus. METHODS:
      Echocardiography and the measurement of plasma TNF-alpha and B-type natriuretic
      peptide (BNP) concentrations, one of the parameters indicating left ventricular
      wall stress, were performed on 176 ESRD patients undergoing maintenance HD (88
      non-diabetic and 88 diabetic patients). RESULTS: The mean plasma TNF-alpha
      concentrations were high, but did not differ between non-diabetic and diabetic
      patients (9.8 +/- 4.3 pg/mL vs. 9.9 +/- 5.4 pg/mL). In non-diabetic patients,
      plasma TNF-alpha concentration correlated positively with interventricular septal
      wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), and
      inversely with left intraventricular dimensions, but did not correlate with left
      ventricular mass index (LVMI). In contrast, in diabetic patients, plasma TNF
      alpha concentration correlated positively with plasma BNP concentration (r=0.821,
      p=0.0001) and left intraventricular dimensions, and inversely with rLVWT (r=
      0.407, p=0.0001) and left ventricular fractional shortening (r=-0.445, p=0.0001).
      CONCLUSIONS: Circulating TNF-alpha is possibly involved in concentric left
      ventricular remodeling in non-diabetic HD patients, whereas it is associated with
      eccentric left ventricular remodeling against sustained pressure and/or volume
      overload in diabetic HD patients.

PMID- 14733410
TI  - Increased placental expression of tissue factor is associated with abnormal
      uterine and umbilical Doppler waveforms in severe preeclampsia with fetal growth
      restriction.
AB  - BACKGROUND: This study investigated whether modifications of placental expression
      of endothelin-1 (ET-1), nitric oxide synthase (NOS) and tissue factor (TF) are
      associated with abnormal Doppler waveforms. METHODS: Fourteen pre-term severe
      preeclamptic (PE) women with fetal growth restriction (FGR) and 14 normal preg
      nant women underwent serial Doppler examination of the uterine and umbilical
      arteries (UA). Placental ET-1 and T expression was evaluated by in situ
      hybridization, NOS by NADPH-diaforase staining and in situ hybridization Doppler
      evaluation was extended to 11 female kidney transplant recipients (Tx), without
      FGR and/or PE, in wh we previously demonstrated a strong modification of
      placental ET-1/NOS vasoactive balance. RESULTS: PE women showed a marked
      reduction of endothelial constitutive NOS (ecNOS) expression in the syncy
      tiotrophoblast layer of all villi, whereas ET-1 expression was unchanged. All
      cases showed abnormal uterine artery blood flow velocimetry, 13 out of 14 PE
      women showed abnormal UA Doppler waveforms. In contrast, all Tx women showed
      normal UA blood velocimetry, all but one woman displayed a normal uterine artery
      waveform pattern. The Doppler velocimetry abnormalities were significantly
      associated with only TF expression, which was markedly increased, exclusively, in
      the endothelial cells within the basal decidua of PE women. CONCLUSIONS: The
      modification of ET-1/NOS vasoactive balance, per se, did not lead to Doppler
      impedance modifica tions in the UA and uterine arteries, observed in pre-term PE
      women with FGR. Instead, Doppler velocimetry modi fications appeared to correlate
      with endothelial cell activation, as revealed by increased TF expression.

PMID- 14733411
TI  - The role of ultrasonography in the assessment of renal function in the elderly.
AB  - BACKGROUND: Ageing is associated with a progressive loss of renal mass and kidney
      length and a decline in glomerular filtration rate (GFR). This study evaluated a
      possible correlation between renal function and kidney size measured by
      ultrasonography (US), and whether the latter helps estimate GFR in the elderly.
      METHODS: Twenty-five medically stable elderly patients (mean age 85 +/- 5 yrs)
      were examined in a geriatric ward at a university hospital. Blood samples were
      taken to determine serum creatinine (Cr) levels. On the same day, 51chromium
      ethylenediamine tetraacetic acid (51Cr-EDTA) clearance was performed as the gold
      standard of GFR. US measured kidney length, transverse and anteroposterior
      dimensions. RESULTS: Serum Cr (r=-0.67; p=0.0002), Cockcroft-Gault formula
      (r=0.82; p<0.0001), absolute length (r=0.51; p=0.008) and volume kidney (r=0.46;
      p=0.02) correlated significantly with GFR. After receiver operating curve (ROC)
      analysis, length was less specific than sensitive in detecting renal impairment.
      Adding length to the Cockcroft-Gault formula did not improve GFR estimation
      (p=0.44). In contrast, adding length to serum Cr levels improved GFR estimation
      (p=0.015). CONCLUSION: In the elderly, kidney length and volume significantly
      correlated with GFR. However, length has a low specificity in predicting renal
      impairment. Therefore, in clinical practice, serum Cr levels and calculated Cr
      clearance are more useful in predicting renal impairment. However, normal kidney
      length can help to exclude renal impairment in the elderly at risk of GFR
      underestimation by a calculated Cr clearance.

PMID- 14733412
TI  - Assessment of tumor-associated trypsin inhibitor (TATI) as a marker of renal
      function.
AB  - BACKGROUND: Low molecular weight (LMW) proteins have been proposed for renal
      function assessment. This study aimed to ascertain the usefulness of tumor
      associated trypsin inhibitor (TATI), a LMW protein (6.200 d), as a glomerular
      filtration rate (GFR) marker. The results were compared with those of beta2
      microglobulin and of creatinine (Cr). METHODS: Renal handling of TATI labelled
      with 125I was first studied in rats. Then, in 198 patients, serum TATI levels and
      GFR (99mTc-DTPA clearance, bladder cumulative method) were determined. To
      evaluate urine excretion, the fractional TATI clearance was determined in 63
      patients. RESULTS: In rats, total body scan showed a large amount of
      radioactivity in the kidneys, but not in other organs. The duration of
      radioactivity demonstrated a peak-time of 11 min. In human beings, the
      relationship between TATI and GFR was similar to that of beta2-microglobulin and
      Cr. The increase in TATI with declining renal function was statistically
      significant, vs. patients with GFR > 100 mL/min, already in the group with GFR 80
      100 mL/min (p < 0.05, Bonferroni-Dunn test). The beta2-microglobulin increase was
      significant in the group with GFR 60-80 mL/min and of Cr in the group with GFR 40
      60 mL/min. In patients with renal failure (GFR < 20 mL/min) TATI increased, vs.
      patients with GFR > 100 mL/min, 13x, beta2-microglobulin 8x and Cr 5x. Urinary
      excretion of TATI, expressed as fractional clearance, was very low increasing
      when GFR fell < 40 mL/min. CONCLUSIONS: The kidney plays an important role in the
      handling of TATI. When GFR fell, the increase in blood levels of TATI was sooner
      and higher than that of beta2-microglobulin and CR. Consequently, TATI can be
      added to the group of renal function markers.

PMID- 14733413
TI  - Adrenomedullin inhibits pressure-induced mesangial MCP-1 expression through
      activation of protein kinase A.
AB  - BACKGROUND: In glomerular hypertension, monocyte chemoattractant protein-1 (MCP
      1) has been implicated in glomerulosclerosis progression. High-pressure load and
      stretch on mesangial cells (MC) are two major effects of increased glomerular
      pressure. We previously reported that pressure per se could induce MCP-1
      expression in cultured MC, suggesting the involvement of glomerular hypertension
      in renal disease progression through MCP-1 expression in MC. We also showed that
      adrenomedullin (AM) inhibited pressure-induced MC proliferation; however, it is
      not clear whether AM alters pressure-induced mesangial MCP-1 expression. In this
      study, we examined the effect of AM on pressure-induced MCP-1 expression in
      cultured rat MC and the mechanism of such action. Using compressed helium,
      pressure was applied to MC placed in a sealed chamber. AM inhibited pressure
      induced MCP-1 mRNA expression, measured by reverse transcribed-polymerase chain
      reaction (RT-PCR), in a dose-dependent manner. This inhibition was in parallel to
      an increase in cellular cyclic AMP (cAMP) levels evoked by AM. The effects of
      forskolin and dibutyryl cAMP mimicked those of AM. Protein kinase A (PKA)
      inhibitor H-89 significantly weakened the effects of AM. AM significantly reduced
      the pressure-induced increase in MCP-1 protein in supernatants of cultured MC,
      measured by enzyme-linked immunosorbent assay (ELISA). Our results suggested that
      AM inhibits pressure-induced mesangial MCP-1 expression through PKA activation.

PMID- 14733414
TI  - Increased 5-lipoxygenase activating protein in immune-mediated experimental
      nephritis.
AB  - BACKGROUND: The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein
      (FLAP) is a prerequisite for subsequent formation of leukotrienes from
      arachidonic acid. METHODS: We investigated the localization of FLAP in a rat
      model of accelerated anti-glomerular basement membrane nephritis and protein
      expression in cultured rat glomerular endothelial cells. RESULTS: As expected, 5
      LO staining was intense and localized exclusively to perinuclear region and
      inside the nucleus of leukocytes and macrophages. In these cells, FLAP
      immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear
      envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was
      also observed in glomerular endothelial cells in early experimental
      glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat
      glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5
      LO protein. FLAP protein was regulated in glomerular endothelial cells by the
      proinflammatory cytokine, interferon-gamma, in a dose-dependent manner.
      CONCLUSION: The unexpected discovery of FLAP in glomerular endothelial cells in
      this model of glomerulonephritis, coupled with our demonstration that oral FLAP
      antagonist therapy reduces proteinuria in human glomerulonephritis and animal
      models of diabetes, provides further impetus to examine the role of this pro
      inflammatory protein in glomerular immune injury.

PMID- 14733415
TI  - Duration of optimal therapy for idiopathic focal segmental glomerulosclerosis.
AB  - We conducted a retrospective study to evaluate the duration of optimal steroid
      therapy in idiopathic focal segmental glomerulosclerosis (FSGS). We evaluated 93
      adult patients (n=65 males) with biopsy proven FSGS. Mean proteinuria was 5.4 +/-
      2.8 gm/dL. Twelve patients were lost at follow-up. Of the remaining 81 patients,
      nephrotic range proteinuria was present in 48 (59%), and 21 (26%) presented with
      renal insufficiency. Of these patients, three (3.9%) experienced spontaneous
      remission. Seven patients were managed symptomatically with ACE inhibitors and
      never received steroids. Of the 71 patients, 32 received >16 weeks of steroid
      therapy, while 39 received <16 weeks of steroid therapy. Twenty-four patients
      (75%) who received >16 weeks of steroid therapy had a complete or partial
      remission, while only 18 (46%) of those with <16 weeks of steroid therapy had a
      steroid response (p=0.001). Patients with more than 25% interstitial fibrosis at
      biopsy also showed significantly lower remission rates (p=0.02). Hypertension,
      hematuria and degree of proteinuria did not significantly affect the response to
      steroid therapy. Univariate logistic regression analysis showed that the factors
      predictive of remission were: (1) steroid therapy duration (p=0.001); (2) serum
      creatinine (Cr) at onset (p=0.001) and; (3) presence of interstitial fibrosis
      (>25%) at initial biopsy (p=0.02). Multivariate logistic regression analysis
      showed that the only factor predictive of remission was steroid therapy duration
      >16 weeks (p=0.001). Therefore, we concluded that patients with idiopathic FSGS
      required treatment for at least 16 weeks, before labeling them as steroid non
      responsive. Patients with interstitial fibrosis have a significantly poor
      response to therapy.

PMID- 14733416
TI  - Erythropoietin requirements: a comparative multicenter study between peritoneal
      dialysis and hemodialysis.
AB  - BACKGROUND: The management of anemia with erythropoietin (EPO) is important in
      the global treatment of dialysis patients. There is a general impression that
      anemia control with EPO is obtained more easily in peritoneal dialysis (PD)
      patients than in hemodialysis (HD) patients. The EPO administration route has to
      be the same to compare the two techniques adequately. METHODS: To compare EPO
      action by subcutaneous (SC) route in HD and PD, 132 stable patients were
      recruited (HD: 69, PD: 63) from six centers, with adequate dialysis criteria
      (Kt/V in HD >1.3; weekly Kt/V in PD >1.8). In a cross-sectional study, the EPO
      dose/week, the number of EPO doses/week, hemoglobin (Hb), ferritin, transferrin
      saturation index (TS), albumin and intact parathyroid hormone (iPTH) were
      analyzed. Iron treatment, comorbidity and ACE inhibitors (ACEI) and angiotensin
      II antagonist (AIIA) treatment were recorded. A multivariate regression model was
      used in the statistical analysis. RESULTS: The mean Hb level was the same in both
      groups, HD 11.6 (1.3) g/dL, PD 11.4 (1.4) g/dL, p=0.3. The SC, EPO doses required
      to obtain the Hb levels were higher in HD than in PD patients, with a difference
      of 64.3 u/Kg/week, statistically significant in the multivariate regression model
      (p=0.001, 95% CI 42.6-86.0). The number of EPO doses/week was also higher in HD
      patients (65% of HD patients with > or = 3 doses, 19% of PD patients with three
      or more doses, p<0.001). TS was similar in both groups, while ferritin was higher
      in HD patients, with a higher percentage of HD patients using intravenous (i.v.)
      iron (HD 77% vs. PD 49%, p=0.001). Serum albumin and iPTH were lower in PD
      patients (p<0.001 and p=0.04, respectively), but the percentage of patients with
      intact parathyroid hormone (iPTH) >500 pg/mL was similar in both groups (HD 17%,
      PD 14%). CONCLUSIONS: With the same administration route, PD patients showed a
      reduced EPO requirement, and less frequent EPO administration than HD patients,
      to obtain the same Hb level. No other factors, except those involved in better
      depuration of erythropoiesis inhibitors in PD, seemed responsible for the
      different EPO requirements.

PMID- 14733417
TI  - Comparative study of intravenous ascorbic acid versus low-dose desferroxamine in
      patients on hemodialysis with hyperferritinemia.
AB  - BACKGROUND: In patients on hemodialysis (HD), parenteral iron improves the
      response to recombinant human erythropoietin (rhuEPO) therapy, but in some
      subjects it produces an iron overload, increasing their morbidity and mortality
      rates. In these cases, iron administration must be discontinued. This study aimed
      to investigate the efficiency of treatment with ascorbic acid (AA) or
      desferroxamine (DFO) to mobilize and reduce iron stores, and to determine the
      effect of these compounds on erythropoiesis. METHODS: We performed a prospective
      and randomized trial over 6 months, which included 27 patients with serum
      ferritin levels >800 ng/mL, TSAT >30% and stabilized hemoglobin (Hb) and rhuEPO
      doses. All patients had previously received parenteral iron (Ferlecit). Nine
      patients received 200 mg of intravenous (i.v.) AA 3 times/week and nine patients
      received 1 mg/Kg/week of DFO; the remaining nine patients were the control group.
      RESULTS: There were no significant differences in iron loss or mobilization due
      to dialysis. When Ferlecit was discontinued, functional iron did not vary and the
      epoetin resistance index (rhuEPO dose/Hb) was reduced by 21% in the i.v. AA
      group. In the DFO and control groups, functional iron levels fell. In the DFO
      group the epoetin resistance index increased by 20%, with no modifications in the
      control group. There was a positive correlation between transaminases and serum
      ferritin. CONCLUSIONS: In HD patients with an iron overload, neither i.v. AA
      administration or low-dose DFO increased iron mobilization or iron loss due to
      dialysis. I.v. AA administration allows elimination of iron from stores without
      any drop in the functional iron produced by discontinuing parenteral maintenance
      iron; it also improves the response to rhuEPO. DFO did not elicit any positive
      effects on erythropoiesis.

PMID- 14733418
TI  - Influence of sevelamer hydrochloride on serum concentration of whole (1-84) and N
      terminally truncated (7-84) parathyroid hormone fragments in hemodialysis uremic
      patients.
AB  - Phosphate retention stimulates parathyroid hormone (PTH) secretion in uremic
      patients. Sevelamer hydrochloride is an aluminium- and calcium-free phosphate
      binder used in the treatment of secondary hyperparathyroidism in uremic patients.
      The influence of the phosphate lowering effect on serum levels of whole PTH-1-84
      and N-terminally truncated PTH-7-84 has not been studied. Seventeen hemodialysis
      (HD) patients (nine male, eight female) with chronic renal failure and serum
      phosphorus concentrations, despite calcium carbonate treatment, >2.0 mmol/L were
      enrolled in this study. Patients did not receive aluminium containing binders.
      Blood samples for serum concentration assessments of calcium, phosphorus, PTH-1
      84 and N-terminally truncated PTH-7-84, carboxyterminal cross-linked collagen
      fragments (Ctx), total (AP) and bone specific alkaline phosphatase activity (BAP)
      were drawn twice: before and after 5-week sevelamer administration (in addition
      to calcium carbonate). Sevelamer treatment was followed by a significant
      reduction in serum phosphorus level (from 2.46 +/- 0.09 to 2.07 +/- 0.10 mmol/L;
      p=0.009), PTH-1-84 level (from 396 +/- 75 to 298 +/- 64 pg/mL; p=0.03) and PTH-1
      84/PTH-7-84 ratio (from 1.78 +/- 0.18 to 1.55 +/- 0.19; p=0.01), while serum PTH
      7-84 levels declined only slightly (from 220 +/- 35 to 183 +/- 25 pg/mL; p=0.11).
      Serum calcium, Ctx concentrations, AP and BAP activity did not change markedly.
      There was a significant positive correlation between changes of phosphorus and
      PTH-1-84 (tau=0.48; p=0.007) or PTH-7-84 concentration (tau=0.43; p=0.02). A 5
      week sevelamer treatment suppressed both PTH-1-84 (change statistically
      significant) and PTH-7-84 (change statistically non-significant) serum
      concentration in HD uremic patients seemingly related to changes in phosphatemia.

PMID- 14733419
TI  - Calcitriol pulse therapy and histology of parathyroid glands in hemodialysis
      patients.
AB  - BACKGROUND: Calcitriol pulse therapy (CPT) is considered the most appropriate
      treatment of secondary hyperparathyroidism (sHPTH). This treatment inhibits
      parathyroid hormone (PTH) synthesis and secretion, suppresses parathyroid cell
      proliferation and controls parathyroid gland growth. However, not much is known
      about the effect of such therapy on parathyroid morphology. METHODS: To
      investigate this, we studied all first parathyroidectomies (PTx, either total or
      subtotal) effected in 30 hemodialysis (HD) patients referred to our surgery
      department by five regional dialysis units in 2000-2001. Six patients were
      excluded from the study because of either the persistence or the precocious
      relapse (in the 1st 6 months post-operation) of sHPTH. Twenty-four HD patients
      were considered eligible as four parathyroid glands were ablated in each patient;
      96 glands were then examined histologically. The cohort consisted of 16 males and
      8 females with a mean age of 54 +/- 13 SD yrs (range 20-73) and a dialysis
      duration of 142 +/- 71 months (range 14-289). Data concerning calcitriol
      treatment (doses, administration route and treatment duration) were collected for
      each patient. The patients were subdivided into two groups according to the
      treatment effected in the months preceding PTx: group A (n=13), treated by either
      intravenous (i.v.) (n=12) or per os (n=1) CPT, and group B (n=11), not treated at
      all with calcitriol or vitamin D sterols. Parathyroid gland morphology and the
      parenchymal cell distribution of the parathyroid glands were evaluated by a
      semiquantitative assessment. Serum intact PTH (iPTH), alkaline phosphatase (AP),
      calcium (Ca) and phosphate (P) levels were studied pre- and post-PTx. RESULTS:
      Chief cells (CC) were found in all glands, either alone or associated with
      oxyphil cells (OC). OC were present in 13 of 24 patients (54%); however, it must
      be underlined that they were present 12 times in group A parathyroid glands
      (92%), and only once in group B (9%) (p<0.01). Nodular hyperplasia was found in
      71% (17/24) of patients: 92% (12/13) in group A, and 45% (5/11) in group B
      (p<0.05). There were no significant differences in age, gender, dialysis
      duration, serum levels of iPTH, AP, Ca and P levels between the two groups.
      CONCLUSIONS: There was a strong association between OC presence in parathyroid
      glands and CPT. Furthermore, nodular hyperplasia appeared to be associated
      significantly with CPT. There is still speculation regarding the meaning of these
      CPT effects on parathyroid gland histology and consequently on sHPTH
      pathophysiology.

PMID- 14733420
TI  - The protean face of renal sarcoid.
AB  - Sarcoidosis is a multisystem disorder of unknown etiology, which may occur in all
      tissues and organs of the body. Clinical presentation may be quite variable and
      affected by race. The most commonly affected system is the lungs with >95% of
      patients displaying such involvement. Renal involvement is uncommon (<2%) and may
      occur in the absence of pulmonary involvement resulting in diagnostic
      difficulties. Here we describe a sequential cohort of patients with differing
      presentations of renal sarcoid with and without additional organ involvement. The
      clinical course and treatment are described.

PMID- 14733421
TI  - Bone morphogenic protein-4 expression in vascular lesions of calciphylaxis.
AB  - Calciphylaxis is characterized by an extensive media-calcification of cutaneous
      and subcutaneous arterioles and capillaries. Recent studies have provided
      evidence that vascular calcification is a process with similarities to bone
      metabolism. Bone morphogenic protein-4 (BMP-4) is physiologically involved in
      bone development and repair. The presence of BMP-4 in atherosclerosis and in
      sclerotic heart valves led us to suggest that BMP-4 is also involved in
      calciphylaxis. A 47-year-old male patient developed end-stage renal failure due
      to chronic glomerulonephritis. He has had two kidney transplants with an
      immunosuppressive regimen consisting of cyclosporine A and steroids. He was
      admitted to our hospital because of an increase in serum creatinine (Cr) and he
      subsequently developed progressive dermal ulcerations. A skin biopsy led to the
      diagnosis of calciphylaxis. Immunohistochemistry for BMP-4 of a skin specimen
      from our patient showed strong cytoplasmic immunoreactivity of intradermal cells
      with clear spatial association to arterioles and hair follicles. Whereas there
      are identified inhibitors and promoters of vascular calcification, the presence
      of BMP-4 has not been demonstrated in calcific uremic arteriolopathy. In contrast
      to atherosclerosis, BMP-4 in calciphylaxis cannot be found in vascular media, but
      in intradermal cells at the border of arterioles and hair follicles. Therefore,
      in calciphylaxis BMP-4 can play the role of a cytokine, a growth factor or a
      media-calcification promoter.

PMID- 14733422
TI  - Hemolytic uremic syndrome after multivisceral transplantation treated with
      intravenous immunoglobulin.
AB  - Post transplant hemolytic uremic syndrome (HUS) secondary to immunosuppressive
      regimen is becoming more common with increasing numbers of organ transplantation.
      We describe a case of refractory HUS secondary to immunosuppression post
      multivisceral transplantation, successfully managed with plasmapheresis and
      intravenous immunoglobulin (IVIG).

PMID- 14733423
TI  - Rhodococcus equi peritonitis in continuous ambulatory peritoneal dialysis.
AB  - The human Rhodococcus equi (R. equi) infection is now emerging, although
      extrapulmonary manifestation and isolation from patients without human
      immunodeficiency virus (HIV) infection remains unusual. Considerable effort is
      required to correctly identify and diagnose this facultative pathogen in patients
      with peritonitis in end-stage renal failure (ESRF) on continuous ambulatory
      peritoneal dialysis (CAPD). In the six cases of R. equi CAPD peritonitis reported
      in this series, diagnoses were made, on average, after 15 days and prolonged
      antibiotic therapy with morbidity in two patients. A diagnosis of R. equi should
      be considered in patients with suspected diphtheroid or Nocardia CAPD
      peritonitis, even with no history of animal contact. This study is the largest
      series on R. equi CAPD peritonitis and highlights the impact of this disease.

PMID- 14733424
TI  - Pierre-Joseph Desault (1738-1795)--a forerunner of modern medical teaching.
AB  - Pierre-Joseph Desault (1738-1795) was the first French professor of clinical
      surgery. He was chief surgeon at La Charite and Hotel-Dieu in Paris, where he
      developed a new method for teaching anatomy and modified the teaching of surgery.
      His fame was due to his dedication and to the number and quality of fellows, who
      included Bichat, Louis, Corvisart, Dupuytren, Percy, Richerand, Petit, Chopart,
      and Gavard. He taught while performing surgery, and his school included up to six
      hundred fellows at a time, practicing in the 1200-bed Hotel-Dieu. He "imprinted"
      his pupils with his professional teaching, his surgical procedures and his
      personal charm.

PMID- 14733425
TI  - P.J. Desault and the birth of nephrology (between 1785 and 1795).
AB  - Desault's genius and methods opened up a field: the medical diseases of the
      urinary tract. Though he was a surgeon and therefore an anatomically based
      clinician, his most important contributions were in renal pathophysiology:
      separation of diseases regarding the formation of urine from those regarding the
      excretion; comparison of anuria with urine retention; polyuria of atrophic
      kidney; fatal dehydration due to polyuria in diabetic patients; oligo anuria
      following excess waterloss from the gut, the lungs...etc. In the last two
      conditions the kidneys might look normal and therefore might be presumed healthy.
      If Desault's work had survived this physiological eruption into renal disorders
      would have been a definitive step of modern nephrology. From a historical point
      of view, one could suspect that Bichat shifted from anatomy and surgery to
      medicine and physiology after having posthumously compiled and edited the
      Desault's book, "Traite des Maladies des voies urinaires".

PMID- 14733426
TI  - Forgotten nephrologists: Leonhard Thurneysser and Hermann Senator.
AB  - Leonhard Thurneysser and Hermann Senator are examples of "Forgotten
      Nephrologists". Leonhard Thurneysser was born in Basel, Switzerland in the 16th
      Century and worked for many years in Berlin. He was a goldsmith, miner, printer,
      astrologist and uroscopist. He traveled all over Europe. His importance stems
      from the physicochemical methods he introduced into uroscopy. He prosposed that
      urine distillates and their residues should be burnt in order to define their
      composition from the colour of the flame. He developed a overcomplicated system
      of fractionated distillations and drew more and more speculative conclusions.
      Hermann Senator lived in the 19th Century. Born and trained in Berlin, he became
      a critical and experienced nephrologist. His observations of "physiological" and
      "pathological" protein excretion in humans became important. Critical
      oberservations in the hospital, experimental testing of derived hypotheses and
      careful analyses of derived concepts characterize his work. He stimulated many
      young physicians to cooperate. Together with Munck he formulated the "Senator
      Munck-Doctrine", according to which current concepts of urine formation as
      postulated by Bowman, Ludwig, Heidenhain et al could be and were unified in a
      "Filtration-Secretion-Reabsorption-Concept".

PMID- 14733427
TI  - Sir Robert Christison (1797-1882): a neglected founder of nephrology.
AB  - Although Robert Christison (1797-1882) of Edinburgh was one of the three main
      pioneers of modern nephrology along with Bright and Rayer, his name much is less
      well known than his compatriots, even in his native Scotland. Amongst many
      contributions to an amazingly wide variety of medical fields in a long and
      distinguished career, he confirmed and extended Bright's work on the nature and
      origins of albuminuria and dropsy, showed that these states might be completely
      reversible, suggested a relationship between acute nephritis, large white and
      granular kidneys, discovered the basis for understanding uremia whilst applying
      chemistry to the study of blood and urine in patients with renal disease,
      described and quantified the anemia of renal failure for the first time, made
      early microscopical examinations of the kidney and urine, and finally described
      the syndrome of acute renal failure from intrinsic renal involvement in response
      to outside noxious stimuli or poisons. Today, it is not easy to discern why he
      has been so overlooked. Possibily, the fact that he had such an enormous output
      in other fields, particularly pharmacology and jurisprudence, on which his fame
      principally rests today, whilst he studied renal diseases for only 25 years of
      his long career. In addition, only one year after his own book on granular kidney
      was published, Pierre Rayer brought out his enormous treatise and even though he
      quoted Christison's results, subsequently tended to be cited even by British
      physicians. Finally, he left no school of pupils to honour and advertize his
      achievements to subsequent generations.

PMID- 14733428
TI  - Charles Edward Isaacs (1811-1860): exploring the details of nephron structure and
      function in the post-Bowman period.
AB  - Charles Edward Isaacs (1811-1860), an anatomist working in New York, undertook a
      series of studies which attempted to define the microscopic structure of the
      nephrons in a variety of species. Given that he published his findings 15 years
      after William Bowman's seminal paper on the subject, he was able to add only a
      few of the finer details to the picture. He observed the continuity of the
      epithelium of the glomerular capsule with that of the proximal tubule and he
      demonstrated that the glomerular tuft is covered by a layer of epithelial cells.
      In a series of studies on human renal function he erroneously concluded that the
      glomerulus must have an excretory function in addition to its filtration function
      and that diuretics act primarily on the glomerlus. The latter conclusion was
      based upon observations of substances not currently categorized as being diuretic
      agents. The absence of a major conceptual advance in the writings of Isaacs
      probably accounts for that fact that his contribution has been largely forgotten.

PMID- 14733429
TI  - Francis Delafield (1841-1915): the original contributions of an American
      investigator to diseases of the kidney.
AB  - The growth of our knowledge of diseases of the kidney has been the work of
      brilliant individuals of talent and passion, who have become some of the most
      respected and best remembered figures in nephrology. Unfortunately, we often
      forget that in many cases there were others, no less brilliant, whose vision and
      passion to study diseases of the kidney was no less intense but whose
      contributions have been forgotten. Francis Delafield (1841-1915) is one of those
      important but overlooked figures. An 1863 graduate of the College of Physicians
      and Surgeons, he continued his studies in London and Berlin, and upon his return
      to New York became a pioneer in histopathology in general and that of kidney
      disease in particular. He provided detailed and accurate microscopic descriptions
      of kidney pathology, made a concerted effort to correlate clinical signs and
      symptoms with kidney lesions and provided a nosological classification of the
      acute and chronic forms of what was then known merely as Bright's disease. During
      his life, he was recognized as the American authority on diseases of the kidney
      and the City of New York acknowledged his contributions by naming a hospital
      after him.

PMID- 14733430
TI  - Extrusomes in ciliates: diversification, distribution, and phylogenetic
      implications.
AB  - Exocytosis is, in all likelihood, an important communication method among
      microbes. Ciliates are highly differentiated and specialized micro-organisms for
      which versatile and/or sophisticated exocytotic organelles may represent
      important adaptive tools. Thus, in ciliates, we find a broad range of different
      extrusomes, i.e ejectable membrane-bound organelles. Structurally simple
      extrusomes, like mucocysts and cortical granules, are widespread in different
      taxa within the phylum. They play the roles in each case required for the
      ecological needs of the organisms. Then, we find a number of more elaborate
      extrusomes, whose distribution within the phylum is more limited, and in some way
      related to phylogenetic affinities. Herein we provide a survey of literature and
      our data on selected extrusomes in ciliates. Their morphology, distribution, and
      possible function are discussed. The possible phylogenetic implications of their
      diversity are considered.

PMID- 14733431
TI  - Expression of GFP-actin leads to failure of nuclear elongation and cytokinesis in
      Tetrahymena thermophila.
AB  - Green fluorescent protein (GFP)-tagged actin was used to investigate the
      distribution and function of actin in Tetrahymena. A strain that expresses both
      GFP-actin and endogenous actin was developed by transformation of Tetrahymena
      thermophila with a ribosomal DNA-based replicative vector. Confocal microscopy of
      living cells and immunogold electron microscopy confirmed localization of GFP
      actin to basal bodies and the contractile ring. Incorporation of the fusion
      protein into these and other actin-related structures correlated with severe
      impairment of macronuclear elongation and cytokinesis. At 30 degrees C
      macronuclear elongation failed to occur in 25% of the transformants despite
      completion of micronuclear division. At 20 degrees C macronuclear elongation
      failed to occur in 2% of the population. Arrest of cytokinesis coincided with
      failure of macronuclear elongation. Arrested cells developed into homopolar
      doublets with two sets of oral structures. This study indicates a requirement for
      actin in nuclear elongation and cytokinesis. Although GFP-actin can interfere
      with the functioning of actin-containing structures, the GFP-actin transformant
      strain can be used to monitor actin distribution and dynamics and is therefore an
      important new tool for further studies of Tetrahymena actin.

PMID- 14733432
TI  - Molecular characterization of nuclear small subunit (18S)-rDNA pseudogenes in a
      symbiotic dinoflagellate (Symbiodinium, Dinophyta).
AB  - For the dinoflagellates, an important group of single-cell protists, some nuclear
      rDNA phylogenetic studies have reported the discovery of rDNA pseudogenes.
      However, it is unknown if these aberrant molecules are confined to free-living
      taxa or occur in other members of the group. We have cultured a strain of
      symbiotic dinoflagellate, belonging to the genus Symbiodinium, which produces
      three distinct amplicons following PCR for nuclear small subunit (18S) rDNA
      genes. These amplicons contribute to a unique restriction fragment length
      polymorphism pattern diagnostic for this particular strain. Sequence analyses
      revealed that the largest amplicon was the expected region of 18S-rDNA, while the
      two smaller amplicons are Symbiodinium nuclear 18S-rDNA genes that contain single
      long tracts of nucleotide deletions. Reverse transcription (RT)-PCR experiments
      did not detect RNA transcripts of these latter genes, suggesting that these
      molecules represent the first report of nuclear 18S-rDNA pseudogenes from the
      genome of Symbiodinium. As in the free-living dinoflagellates, nuclear rDNA
      pseudogenes are effective indicators of unique Symbiodinium strains. Furthermore,
      the evolutionary pattern of dinoflagellate nuclear rDNA pseudogenes appears to be
      unique among organisms studied to date, and future studies of these unusual
      molecules will provide insight on the cellular biology and genomic evolution of
      these protists.

PMID- 14733433
TI  - An improved description of Strombidium sulcatum Claparede & Lachmann, 1859
      (Ciliophora) from slides of Faure-Fremiet, and a designation of type material.
AB  - Strombidium sulcatum, the type species of the genus, is examined using silver
      stained material made by Faure-Fremiet in the 1950s and 1960s. We found that the
      stained specimens possessed a prominent protuberance, as previously described;
      the number of anterior polykinetids (APk) differed between the accounts (15 this
      study, 12 previous reports); although previously illustrated, no contractile
      vacuole was observed; and the macronuclear shape, position, and size differed
      from those previously reported. Our work provides the first detailed re-analysis
      of the silver-stained material of S. sulcatum. We use data on S. sulcatum to
      distinguish it from a morphologically similar species, Strombidium inclinatum.
      Type material for S. sulcatum has been deposited in the Natural History Museum,
      London.

PMID- 14733434
TI  - Caspase-like activity is required for programmed nuclear elimination during
      conjugation in Tetrahymena.
AB  - During conjugation in the binucleate ciliate, Tetrahymena thermophila, the old
      macronucleus is eliminated as new macronuclei and micronuclei are ontogenetically
      derived from the zygote nucleus. The mechanism of programmed nuclear elimination
      in ciliates may be related to the mechanism of apoptosis in higher organisms
      since its chromatin undergoes major condensation, its DNA is digested into
      nucleosome-sized fragments, and it stains positively for TUNEL. The present study
      explores whether caspases are involved in programmed macronuclear degradation in
      Tetrahymena. We show here that caspase-like activity is detectable using two
      specific colorimetric substrates, and that the activity is reduced with specific
      caspase inhibitors. In addition, using the fluorigenic substrate PhiPhiLux,
      active caspase-like activity is detected in living cells, localized to
      cytoplasmic vesicles; activity is not detected in pre- or post-condensed
      macronuclei. Finally, three different inhibitors of caspase activity cause a
      block to macronuclear chromatin condensation and elimination. Therefore, a
      caspase-like enzyme activity is necessary for regulating macronuclear elimination
      in Tetrahymena. These data support the possibility that macronuclear elimination
      is related, evolutionarily, to regulated cell death in multicellular organisms.

PMID- 14733435
TI  - Observations on the life stages of Sphaerothecum destruens n. g., n. sp., a
      mesomycetozoean fish pathogen formerly referred to as the rosette agent
      [correction].
AB  - The rosette agent is an obligate intracellular parasite that causes morbidity and
      mortality in salmonid fish. In laboratory cultures, the spore stage (2-6 microm
      diam.) replicates in a salmonid cell line by sequential asexual division, giving
      rise to daughter cells. If infected cell cultures are transferred to distilled
      water, the spore stage undergoes internal division to give rise to at least 5
      cells each of which develops into a uniflagellated zoospore with a body of
      approximately 2 microm and a flagellum approximately 10 microm long.
      Zoosporulation does not occur in cell culture medium alone, artificial seawater,
      or phosphate-buffered saline. This parasite is currently classified as a member
      of the Class Mesomycetozoea (formerly Ichthyosporea) based on phylogenetic
      analyses of the small subunit ribosomal DNA of three different isolates from
      fish. Given these new morphological observations combined with the available
      molecular phylogenetic data on other mesomycetozoeans, we propose to classify the
      rosette agent as Sphaerothecum destruens, n. g., n. sp. This new genus has unique
      features including (1) intracellular development of spore stages in various
      organs eliciting a host granulomatous response; and (2) the differentiation of
      mature spores into multiple, flagellated zoospores. Taken together, these
      characteristics clearly distinguish it from the closely related genera
      Dermocystidium and Rhinosporidium.

PMID- 14733436
TI  - A marine dinoflagellate, Amphidinium eilatiensis n. sp., from the benthos of a
      mariculture sedimentation pond in Eilat, Israel.
AB  - A species of Amphidinium bloomed in a mariculture sedimentation pond that was
      used to grow bivalves near the Gulf of Eilat, Israel. Its overall length averaged
      13 microm, the hypocone was 11 microm, and its width was 8 microm. It has a
      ventral ridge. The sulcus begins at the longitudinal flagellar pore and does not
      project forward in the apex toward the transverse flagellar pore and left margin
      of the cingulum. The sulcus is a very shallow groove that projects variably about
      a third of the body length toward the antapex. The cingulum is a deep groove as
      it circles the cell from the left ventral side to the dorsal side and then
      becomes very shallow on the right ventral side as it arches posterior toward the
      longitudinal flagellar pore. Using a modified method for studying dinoflagellate
      chromosomes in the SEM, we observed 31 chromosomes. The plastid is dorsal and
      peripheral with 6 ventrally projecting peripheral digital lobes that wrap around
      the sides of the ventral and posterior nucleus. Amphidinium eilatiensis n. sp. is
      morphologically closest to Amphidinium carterae and Amphidinium rhynchocephalum,
      but it does not have the obvious thecal plates or polygonal units described for
      the former species. Instead, it has a series of spicules, bumps, and ridges on
      its surface. It differs from A. rhynchocephalum by two morphological characters:
      surface morphology and gross plastid architecture. The amplified fragments of the
      rDNA from A. eilatiensis n. sp. isolated from 2 separate sedimentation ponds in
      Eilat include the 3'- end of the SSU rDNA (about 100 nt), the whole ITS region
      (ITS1 + 5.8S + ITS2) and the 5'-end of the LSU rDNA (about 900 nts). The total
      length of the sequences ranged from 1,460 nt. (A. eilatiensis isolate #1) to
      1,461 nts. (A. eilatiensis isolate #2). The latter sequences are identical, the
      difference in length being due to three insertions. Amphidinium eilatiensis is
      genetically more closely related to A. carterae than to A. klebsii, with
      respectively 2.36% and 6.93% of sequence divergence.

PMID- 14733437
TI  - New contributions to two heterotrichous ciliates, Folliculina simplex (Dons,
      1917), Condylostoma curva Burkovsky, 1970 and one licnophorid, Licnophora
      lyngbycola Faure-Fremiet, 1937 (Protozoa, Ciliophora): descriptions of morphology
      and infraciliature.
AB  - The living morphology and infraciliature of two heterotrichous and one
      licnophorid ciliates from the north China seas, i.e. Folliculina simplex (Dons
      1917), Condylostoma curva Burkovsky, 1970, and Licnophora lyngbycola Faure
      Fremiet, 1937, were investigated using protargol impregnation and in vivo
      observations. Updated diagnoses and redescriptions of each species are provided.
      The improved diagnosis of Folliculina simplex is as follows: blue-greyish to blue
      greenish Folliculina with broad and unequal-sized peristomial lobes; adoral zone
      of membranelles comprises about 400 membranelles and forms two-and-half turns
      within buccal cavity; paroral membrane extends entire length of adoral zone of
      membranelles; about 50 somatic kineties in mid-body; single ovoid to ellipsoid
      macronucleus and several micronuclei; lorica vase-shaped, about 150-250 microm
      long, often with jelly-like covering and inconspicuous neck; marine habitat.
      Improved diagnosis for Licnophora lyngbycola: marine Licnophora with cup-shaped
      body and glabrous adhesive disc with which the organism attaches to the filaments
      of the colourless cyanobacterium Lyngbya; in vivo 80-130 microm long; about 140
      adoral membranelles, one micronucleus and a single C-shaped, moniliform
      macronucleus consisting of about 14 nodules; two specialized dorsal kineties;
      five peripheral rings on adhesive disc, the 2nd, 3rd, and 5th (outermost) which
      are incomplete. Based on the Qingdao population, an improved diagnosis for
      Condylostoma curva is supplied: yellow-brownish Condylostoma with oval to
      elongated body shape; about 150-350 microm long in vivo; about 68-108
      membranelles in adoral zone of membranelles, 4-8 frontal cirri, 22-32 somatic
      kineties; macronucleus moniliform with 5-13 nodules; with cortical granules;
      marine habitat.

PMID- 14733439
TI  - RpoA: a useful gene for phylogenetic analysis in diatoms.
AB  - The aim of this study was to compare the usefulness of two chloroplast-encoded
      genes (rpoA and rbcL) and the nuclear-encoded small subunit (SSU) ribosomal RNA
      for reconstructing phylogenetic relationships among diatoms at lower taxonomic
      levels. To this end, the rpoA and rbcL genes for selected centric and pennate
      diatoms were sequenced. The new rpoA and rbcL sequences, and an existing nuclear
      encoded SSU rRNA data set, were subjected to weighted/unweighted parsimony,
      maximum likelihood, minimum evolution, and Bayesian analyses. All of the tree
      building methods employed showed, based on the support values, that the rpoA gene
      was the most useful, relative to the rbcL and SSU rRNA genes, in determining
      phylogenetic relationships among the sampled diatoms. The support values for the
      relationships among the pennate lineages were, in many instances, greater in the
      rpoA trees than in the SSU rRNA trees. These results suggest that rpoA might be
      of value in determining phylogenetic relationships among pennate lineages.

PMID- 14733438
TI  - Morphological and phylogenetic studies of marine Myxobolus spp. from mullet in
      Ichkeul Lake, Tunisia.
AB  - Six species of the genus Myxobolus (Myxozoa) from the marine environment were
      collected from two species of mullet (Mugil cephalus and Liza ramada) in Ichkeul
      Lake, Tunisia. Four of these species were described previously (Myxobolus
      bizerti, Myxobolus ichkeulensis, Myxobolus spinacurvatura, and Myxobolus
      episquamalis) and two (Myxobolus exiguus and Myxobolus muelleri) are redescribed.
      The small subunit ribosomal (18S rDNA) sequences of these six myxozoans were
      obtained and compared to traditional criteria used in the identification and
      taxonomy of myxozoan species (such as spore morphology, host specificity, and
      tissue tropism). A distance analysis of 1,600-1,700 base pairs of the 18S rDNA of
      the six species indicates that they formed a monophyletic group separate from
      Myxobolus spp. found as parasites of freshwater fish. The sequence analyses also
      confirm that these morphologically different Myxobolus spp. that infect mullet
      represent different species. Lastly, M. exiguus and M. muelleri, which were found
      in the same host, exhibit clear differences in spore morphology but sequencing of
      two different regions of the 18S rDNA show they are closely related. These
      results demonstrate the utility of DNA sequence data in providing more detailed
      relationships among the Myxobolus species based upon existing morphological
      taxonomic approaches. We suggest that future descriptions of Myxobolus spp.
      provide both careful spore descriptions as part of the traditional criteria but
      also 18S rDNA sequence data that will aid in situations where morphological
      details may be absent or misleading.

PMID- 14733440
TI  - Redescription of the sarcocysts of Sarcocystis rileyi (Apicomplexa:
      Sarcocystidae).
AB  - The intermediate hosts for Sarcocystis rileyi (Stiles 1893) Minchin 1913 are
      ducks (Anas spp.), and the striped skunk (Mephitis mephitis) is its definitive
      host. The structure of sarcocysts from an experimentally infected shoveler duck
      (Anas cylpeata) fed sporocysts from an experimentally-infected M. mephitis was
      studied and compared with type specimens from a naturally infected duck. The
      experimentally infected duck was killed 154 d after feeding sporocysts. By light
      microscopy the sarcocyst wall was 3-5 microm thick with indistinct villar
      protrusions. Ultrastructurally, the sarcocyst wall was a type-23 cyst wall with
      anastomosing villar protrusions that were up to 7.5 microm long. The villar
      projections contained filamentous structures. The bradyzoites were 12-14 microm
      long. Structurally, the sarcocyst from the naturally infected and experimentally
      infected ducks appeared similar.

PMID- 14733441
TI  - Small subunit ribosomal DNA suggests that the xenophyophorean Syringammina
      corbicula is a foraminiferan.
AB  - Xenophyophorea are giant deep-sea rhizopodial protists of enigmatic origins.
      Although species were described as Foraminifera or sponges in the early
      literature, the xenophyophoreans are currently classified either as a class of
      Rhizopoda or an independent phylum. To establish the phylogenetic position of
      Xenophyophorea, we analysed the small subunit (SSU) rRNA gene sequence of
      Syringammina corbicula Richardson, a newly described xenophyophorean species from
      the Cape Verde Plateau. The SSUrDNA analyses showed that S. corbicula is closely
      related to Rhizammina algaeformis, a tubular deep-sea foraminiferan. Both species
      branch within a group of monothalamous (single-chambered) Foraminifera, which
      include also such agglutinated genera as Toxisarcon, Rhabdammina, and Saccammina,
      and the organic-walled genera Gloiogullmia and Cylindrogullmia. Our results are
      congruent with observations of similar cytoplasmic organisation in Rhizammina and
      Syringammina. Thus, the Xenophyophorea appear to be a highly specialised group of
      deep-sea Foraminifera.

PMID- 14733442
TI  - Recruiting immigrants for long-term care nursing positions.
AB  - Recent immigrants and workers in foreign countries are two groups frequently
      identified as potential sources of new workers for nursing positions in long-term
      care (LTC). Recruiting workers directly from other countries, either permanently
      or temporarily, is difficult because of restrictive visa classifications; is
      unlikely to impact significantly the worker shortage; and may have risks that
      outweigh the potential rewards. On the other hand, with targeted recruitment and
      retention efforts, the nation's rapidly growing immigrant population (the so
      called "New Americans") can become an even more important source of labor for
      frontline LTC workers. To be successful employees in LTC, however, New Americans
      will have to overcome a variety of cultural and language barriers. Equally
      important, the institutions and agencies that comprise the LTC system must
      exhibit a higher level of sensitivity to cultural differences. Efforts to
      recruit, train, and retain New Americans for positions in LTC present win-win
      opportunities and should be expanded.

PMID- 14733443
TI  - Political and organizational barriers to satisfying low-income U. S. seniors'
      need for affordable rental housing with supportive services.
AB  - A substantial share of the low-income older tenants who occupy U. S. government
      subsidized rental housing has physical and cognitive limitations. These older
      tenants are often women living alone in their 70s and 80s, who need help
      obtaining community-based services, demand-responsive transportation, help with
      apartment housekeeping and maintenance, self-care assistance, and design
      modifications made to their dwellings. Other low-income and frail older persons
      who have large housing expense burdens or occupy physically deficient dwellings
      also need affordable rental housing with these supportive services. The unmet
      supportive service needs of these groups persist even as this country's major
      political and professional stakeholders are aware of their problems and have
      solutions. This paper examines five major political and organizational barriers
      that have restricted the availability of supportive services in affordable rental
      developments. It offers 12 policy recommendations.

PMID- 14733444
TI  - Policymaking for diversity among the aged in India.
AB  - Population aging is occurring rapidly in India, and the implications of an aging
      society are likely to be experienced in an adverse manner unless immediate steps
      are taken to provide social security for all of India's older population. Current
      provision by central and state governments is grossly inadequate. This article
      analyzes the major Indian states across three income groups and describes the
      differences and inequalities across states and rural/urban areas with regard to
      income, living arrangements, pension benefits, etc. The efforts by central and
      state governments to meet the needs of older persons are outlined and critiqued.
      Suggestions are made for the establishment of more equitable income security, and
      health and social services schemes.

PMID- 14733445
TI  - Powerlessness of older people in Hong Kong: a political economy analysis.
AB  - Gerontologists agree that old age can be associated with an increase in
      powerlessness both in the personal domain and in the social and political fields.
      This paper is an attempt to understand the concept of powerlessness in old age
      within a political economy theoretical framework. The paper argues that the
      powerlessness of older people is not biologically determined. Rather, it is
      socially constructed. It has its roots in the social, economic, and political
      structure of society. For this reason, the paper argues that (a) the capitalist
      economic system discriminates against and marginalizes older people in the labor
      market. The current unfavorable economic climate will make the economic situation
      of older people worse. (b) The residual welfare system does not counteract the
      unfavorable impact of the economic system. Rather, it deprives older people of
      the necessary financial resources and social service supports that would enable
      them to lead independent and dignified lives. (c) The authoritarian political
      system creates adverse conditions that make it very difficult for older people to
      participate in the decision-making process on issues that affect their lives, as
      well as on broader political issues that affect the whole of society. It is the
      interplay among these economic, social, and political forces in Hong Kong that
      creates the political economy of powerlessness in old age and prevents older
      people from using their powers to master and control their lives.

PMID- 14733446
TI  - Licensing and training requirements for direct care workers in Japan: what can
      the United States and Japan learn from each other?
AB  - Shortages of direct care workers have been of concern both in the United States
      and in Japan. This article compares issues surrounding long-term care provisions
      in the two countries and introduces Japan's unique licensure and certificate
      system for direct care workers. Japan has established three levels of direct care
      worker certificates and a direct care licensure, which can be potentially used as
      a career ladder. Studies show that this system has resulted in different work
      conditions and benefits between different certificate and licensure levels but
      had a limited impact on hourly wage and task differentiation. Implications for
      the United States are also discussed.

PMID- 14733447
TI  - Roles and relationships: a psychoeducational approach to reviewing strengths and
      difficulties in adulthood functioning.
AB  - The authors developed a psychoeducational protocol to help psychiatric patients
      review their patterns of interpersonal relationships. The conceptual framework is
      based on the Adult Personality Functioning Assessment (Hill, Fudge, Harrington,
      Pickles, & Rutter, 1995; Hill, Harrington, Fudge, Rutter, & Pickles, 1989). Seven
      domains of functioning are addressed: friendships, romantic relationships, family
      relationships, social contacts, therapeutic relationships, relationships with
      addictive substances and activities, and work. The intervention aims at fostering
      participants' reflectiveness about their relationships to enhance their capacity
      for social support. The introduction sets the protocol in context; an annotated
      version of patient materials includes commentary on each domain.

PMID- 14733448
TI  - Borderline personality organization in violent offenders: correlations of
      identity diffusion and primitive defense mechanisms with antisocial features,
      neuroticism, and interpersonal problems.
AB  - Although theoretical assumptions and empirical evidence suggest an association
      between borderline personality disorder (BPD) and antisocial behavior or even
      antisocial personality disorder (APD), there is no study relating the
      psychodynamic aspects of BPD to antisocial behavior. In this study, the authors
      tested the correlation between the structural criteria of borderline personality
      organization (BPO)--that is, identity diffusion, primitive defense mechanisms,
      and reality testing--and antisocial features, neuroticism, and interpersonal
      problems. A sample of imprisoned violent offenders (N = 91) was studied using the
      Antisocial Personality Questionnaire (APQ), the Borderline Personality Inventory
      (BPI), the Neo-Five-Factor-Inventory (Neo-FFI), and the Inventory of
      Interpersonal Problems (IIP). Significant correlations were predicted and found
      between the BPI scales of identity diffusion, primitive defense mechanisms,
      impaired reality testing, and fear of closeness and antisocial features,
      neuroticism, agreeableness, and interpersonal problems. The results are
      consistent with both object relations theory and attachment theory.

PMID- 14733449
TI  - Long-term treatment of an addictive personality.
AB  - There is infrequent discussion of long-term psychotherapy of persons with
      addiction, particularly in the self-psychology literature. In addition, some
      question whether long-term psychotherapy can be helpful in severe psychiatric
      disorders. The author describes the treatment of a woman with multiple diagnoses,
      including bulimia and alcohol and drug addiction, which took place over a period
      of almost 7 years. These issues are addressed from a self-psychological
      perspective, with progression of the treatment from early facilitation of a
      selfobject transference to more intense selfobject transference
      countertransference states. Behavioral interventions (e.g., recommendation of
      inpatient chemical dependency treatment) are also discussed. The author describes
      the patient's dramatic progress and subsequent regression. Finally, there is a
      discussion of the addiction from self-psychological and biological perspectives
      of this woman's particular developmental and treatment issues, as well as a
      discussion of the confrontation and limit setting in a self-psychologically
      oriented treatment.

PMID- 14733450
TI  - Psychoanalytic practice and the religious patient: a current perspective.
AB  - Via a national survey and in-depth interviews, the author investigated training
      psychoanalysts' views on religion and spirituality and the impact of such views
      on their treatment practices. The training analysts surveyed described being
      appreciative of a patient's religious or spiritual worldview when it allowed for
      flexibility in its theological tenets or when it played a psychologically
      supportive role. In most instances, empathy for a suffering human being together
      with the desire to enter a patient's subjective field of experience overrode
      analysts' personal and professional biases vis-a-vis religious involvement, when
      these were present.

PMID- 14733452
TI  - EEG abnormalities and outcome in first-episode psychosis.
AB  - OBJECTIVE: There is widespread consensus that the EEG is not useful for the
      detection of clinically relevant abnormalities in patients with psychosis. Given
      that the EEG records brain dysfunction, this study examines whether an abnormal
      EEG in first-episode psychosis patients is associated with poorer prognosis,
      compared with a normal EEG. METHOD: At their initial assessment, 61 patients with
      first-episode psychosis had an EEG classified according to the following modified
      Mayo Clinic system: normal, essentially normal (that is, one or more elements of
      questionable normality), or dysrhythmia (grade I to V). We assessed psychiatric
      symptoms using the Scale for Assessment of Negative Symptoms (SANS) and the Scale
      for Assessment of Positive Symptoms (SAPS) on entry and after 1 year of
      treatment. Psychosis is considered to have remitted if there are no, or minimal,
      psychotic symptoms (that is, a rating of 2 or less on every SAPS global rating),
      maintained for 1 month. RESULTS: At the end of 1 year, 19/21 (90.5%) patients
      with a normal EEG had a remission of their positive symptoms, compared with 18/28
      (64.3%) of those with an essentially normal EEG and only 7/12 (58.3%) of those
      with dysrhythmia. Negative symptoms were reduced by more than 50% in 11/18
      (61.1%) patients with a normal EEG, compared with 10/28 (35.7%) patients with an
      essentially normal EEG. None of the 8 patients with dysrhythmia on their EEG
      experienced reduced negative symptoms. CONCLUSION: The above findings suggest
      that an abnormal EEG in patients with first-episode psychosis is associated with
      a poorer prognosis.

PMID- 14733451
TI  - Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia:
      antipsychotic efficacy and extrapyramidal safety during the first 24 hours of
      treatment.
AB  - OBJECTIVE: To determine the antipsychotic efficacy and extrapyramidal safety of
      intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of
      treatment of acute schizophrenia. METHOD: Patients (n = 311) with acute
      schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0
      mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54).
      RESULTS: After the first injection, i.m. olanzapine was comparable to i.m.
      haloperidol and superior to i.m. placebo for reducing mean change scores from
      baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9
      olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, 
      3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,
      13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9
      haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale
      at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients
      treated with i.m. olanzapine had significantly fewer incidences of treatment
      emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not
      akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients
      treated with i.m. haloperidol; they also required significantly less
      anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean
      extrapyramidal symptoms (EPS) safety scores improved significantly from baseline
      during i.m. olanzapine treatment, compared with a general worsening during i.m.
      haloperidol treatment (Simpson-Angus Scale total score mean change: -0.61
      olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score
      mean change: -0.27 olanzapine vs 0.01 haloperidol; P < 0.05). CONCLUSION: I.m.
      olanzapine was comparable to i.m. haloperidol for reducing the symptoms of acute
      schizophrenia during the first 24 hours of treatment, the efficacy of both being
      evident within 2 hours after the first injection. In general, more EPS were
      observed during treatment with i.m. haloperidol than with i.m. olanzapine.

PMID- 14733453
TI  - Impact of antidepressant side effects on adolescent quality of life.
AB  - OBJECTIVE: This study examines the relative impact of antidepressant side effects
      on adolescents with a history of major depression. METHODS: We used Q-sort
      methodology to capture the opinions of adolescents with a history of depression
      (n = 22), adults with a history of depression (n = 20), healthy adolescents (n =
      20), and clinicians (n = 18) on the impact of 40 common antidepressant side
      effects. We asked subjects to force rank the side effects, judging each side
      effect on its relative impact on their daily lives. We also examined the impact
      of these side effects on health status and medication compliance. Primary
      analyses compared adolescents with depression with the other groups on their mean
      rankings for each of the 40 side effects. Secondary analyses included paired
      comparisons for ratings on health status and compliance. RESULTS: Although all
      groups ranked syncope and vomiting among the worst 5 side effects, significant
      differences were found between the groups on other side effects, such as anxiety,
      sleepiness, and hair loss. Based on the side effect with the most negative
      impact, adolescents with depression judged their own compliance (mean = 22%) to
      be higher than predicted by clinicians (mean = 11%). There were no significant
      differences between the groups on the mean rating of health status. CONCLUSIONS:
      Adolescents with depression, adults with depression, healthy adolescents, and
      clinicians agreed on the negative impact of 2 side effects: vomiting and syncope.
      Q-sort methodology provides valuable insight into the similarities and
      differences in opinion regarding the potential impact of side effects in patient
      groups.

PMID- 14733454
TI  - Violence by psychiatric patients: the impact of archival measurement source on
      violence base rates and risk assessment accuracy.
AB  - OBJECTIVE: This study examined the impact of using various archival sources of
      violence data on the recorded base rate of violence and on the accuracy of
      violence risk assessments in a sample of civil psychiatric patients. METHOD:
      Violence in the community, after release from involuntary hospitalization, was
      measured with 3 types of archival data: criminal records, psychiatric hospital
      readmission records, and readmission records from multiple general hospitals.
      RESULTS: Findings indicated that the different measurement sources each
      identified unique incidents of violence, which were correlated moderately or not
      at all with one another, and that the estimated base rate of violence varied
      substantially as a function of outcome source. Not surprisingly, using a
      combination of sources identified the highest base rate of violence. Predictive
      validity estimates also varied widely under different measurement procedures and
      were more stable when a combination of sources was used. CONCLUSIONS: It is
      important in practical and research terms for studies of psychiatric patient
      violence to use multiple sources of outcome data.

PMID- 14733455
TI  - Medicated anxious children: characteristics and cognitive-behavioural treatment
      response.
AB  - OBJECTIVE: To determine whether individual and family characteristics of children
      with anxiety disorders who take psychotropic medications differ from those that
      are unmedicated and whether there is a differential response to cognitive
      behavioural therapy (CBT). METHOD: Children ages 8 to 12 years (n = 102: 18
      medicated, 84 unmedicated) were recruited in a specialized outpatient clinic over
      a 3-year period. All had a primary diagnosis of an anxiety disorder. Comparisons
      were done using t-tests for continuous measures and chi-square tests for discrete
      measures. Treatment-related changes were assessed using repeated measures
      analyses of variance. RESULTS: Medicated and unmedicated groups did not differ by
      age, sex, socioeconomic status, or diagnostic profile. Initial ratings of anxiety
      symptoms, depressive symptoms, and global functioning were comparable. Greater
      family dysfunction and family frustration were reported in medicated children.
      With treatment, both groups improved symptomatically and showed improved family
      functioning. Families of medicated children showed a greater reduction in
      frustration than families of unmedicated children, whereas unmedicated children
      showed greater gains in global functioning. CONCLUSIONS: Initial family
      functioning of medicated children seems to show more disturbances. Both medicated
      and unmedicated children can benefit from CBT. Further studies of differential
      treatment effects for medicated and unmedicated children are indicated.

PMID- 14733456
TI  - From chlorpromazine to clozapine--antipsychotic adverse effects and the
      clinician's dilemma.
AB  - The pharmacotherapy of schizophrenia remains an ongoing challenge for researchers
      and clinicians alike. Current medications remain suboptimal to effectively treat
      this illness despite the recent surge of what are considered to be better
      antipsychotics: the atypicals. The atypicals cause fewer extrapyramidal symptoms
      and tardive dyskinesia, but there is growing concern regarding the significant
      long-term metabolic and cardiac adverse effects of these novel antipsychotics.
      There are differences among the atypicals in their propensity to produce these
      adverse effects, and clinicians should weigh the risk-benefit ratio for each drug
      with each individual patient. Diabetes, heart disease, obesity, and unhealthy
      lifestyle choices are on the rise in the general population, and individuals with
      chronic schizophrenia are even more at risk. The dilemma clinicians face in
      trying to avoid the neurological morbidity of the typicals (extrapyramidal side
      effects and tardive dyskinesia) is the risk of consequently exposing patients to
      both the morbidity and potential mortality of the atypicals (cardiovascular,
      endocrine, and metabolic adverse effects). The importance of baseline
      investigations and monitoring at regular intervals as well as identification of
      patients at risk for obesity, diabetes, and cardiovascular morbidity has become
      crucial. Informed decision making is essential for successful antipsychotic
      pharmacotherapy. For a condition, which often necessitates long-term
      pharmacotherapy, the importance of prevention and (or) minimization of morbidity
      and mortality related to adverse effects of such pharmacotherapy cannot be
      understated.

PMID- 14733457
TI  - Unicorns do exist: a tutorial on "proving" the null hypothesis.
AB  - Introductory statistics classes teach us that we can never prove the null
      hypothesis; all we can do is reject or fail to reject it. However, there are
      times when it is necessary to try to prove the nonexistence of a difference
      between groups. This most often happens within the context of comparing a new
      treatment against an established one and showing that the new intervention is not
      inferior to the standard. This article first outlines the logic of
      "noninferiority" testing by differentiating between the null hypothesis (that
      which we are trying to nullify) and the "nill" hypothesis (there is no
      difference), reversing the role of the null and alternate hypotheses, and
      defining an interval within which groups are said to be equivalent. We then work
      through an example and show how to calculate sample sizes for noninferiority
      studies.

PMID- 14733458
TI  - Association of substance abuse and depression among adolescent psychiatric
      inpatients.
AB  - OBJECTIVE: To determine whether depression levels differ among suicide-attempting
      and non-suicide-attempting adolescent inpatients in relation to their alcohol
      use. METHOD: Ninety-eight adolescents hospitalized at a midwestern psychiatric
      hospital completed the Children's Depression Inventory and the Rutgers Alcohol
      Problem-Drinking Index (RAPI). Based on RAPI scores, adolescents were classified
      as heavy drinkers (n = 36) or light drinkers and nondrinkers (n = 62). RESULTS:
      Heavy drinkers had significantly more depression than those who were classified
      as light drinkers or nondrinkers regardless of suicide-attempting status.
      CONCLUSIONS: The results demonstrate a positive association between depression
      levels and problems with alcohol in adolescents, indicating that youth who both
      suffer from depression and abuse alcohol may be at higher risk for a suicide
      attempt.

PMID- 14733459
TI  - Improving the Mood Disorder Questionnaire to detect bipolar II disorder.

PMID- 14733460
TI  - Mnemonic for the diagnosis of hypomania associated with bipolar II disorder.

PMID- 14733461
TI  - Aripiprazole-induced improvement in tardive dyskinesia.

PMID- 14733462
TI  - Dependent personality disorder as a marker of "battered husband syndrome": a case
      exemplar.

PMID- 14733463
TI  - Visually enhanced psychosexual therapy (VEST) in a multicultural community.

PMID- 14733464
TI  - What kind of dentist do you want to be?

PMID- 14733465
TI  - Effects of fissure cleaning methods, drying agents, and fissure morphology on
      microleakage and penetration ability of sealants in vitro.
AB  - PURPOSE: The purpose of this in vitro study was to determine the effect of
      different cleaning methods and the use of post-etching drying agents, as well as
      the influence of fissure types on the microleakage and penetration ability of
      fissure sealants. METHODS: Ninety extracted human molar teeth were randomly
      divided into 9 groups of 10 each. The treatment groups were defined by the
      combination of different cleaning methods (traditional pumice prophylaxis, air
      abrasion with Prophyflex, and air abrasion with Airflow handy) and different
      drying agents (no drying agent, alcohol 99%, and acetone 99.5%). The teeth were
      thermocycled (5,000 cycles at 5 degrees C-55 degrees C) and were then immersed in
      a solution of 5% methylene blue for 24 hours. Microleakage, penetration ability,
      and fissure types were examined after sectioning. Multiple regression analyses
      were used for statistical analysis. RESULTS: No significant difference was found
      in microleakage and the penetration ability between the use of different cleaning
      methods and sealant placement with or without drying agents (P>.05). Y2 fissure
      type exhibited significantly higher unfilled areas than other fissure types
      (P<.001). CONCLUSIONS: Neither air abrasion with acid etching nor the use of post
      etching drying agents decreased microleakage and improved the penetration ability
      of sealants significantly compared to the conventional sealant application.
      Fissure type was significantly related to the penetration ability of sealants.

PMID- 14733466
TI  - The effects of cavity preparation and lamination on bond strength and fracture of
      tooth-colored restorations in primary molars.
AB  - PURPOSE: This in vitro study compared bond strength and fracture modes of tooth
      colored restorations in 2 types of cavity preparations in human primary molars.
      METHODS: Standardized Class II cavities (40 dovetail and 40 box-only
      preparations) in extracted human primary molars were restored with packable
      composite resin (PC), resin-modified glass ionomer cement (RMGIC), resin-modified
      glass ionomer/packable composite resin laminate (RMGIC/PC), or resin-modified
      glass ionomer/packable composite resin laminate with an experimental bonding
      agent, K-14 (RMGIC/K-14/PC). The ultimate load at fracture was measured on
      marginal ridges, and fractured surfaces were examined microscopically. RESULTS:
      The mean (+/-SD) ultimate load at fracture (ULF, in Newtons) of PC and RMGIC/K
      14/PC in box-only preparations (400+/-98; 386+/-82) did not differ significantly
      from that found in dovetail preparations (377+/-80; 317+/-92), and the mean ULF
      of RMGIC and RMGIC/PC in box-only preparations (307+/-44; 325+/-72) did not
      differ significantly from that in dovetail preparations (352+/-71; 353+/-70). No
      interactions were seen between materials and preparations (P=.09). Fracture modes
      for restorations in dovetail (predominantly mixed) and box-only preparations
      (predominantly mixed and adhesive) differed significantly (P=.003), but not
      between restorative procedures (P=.052). CONCLUSIONS: Tooth-colored restorations
      placed in vitro in box-only preparations did not differ in fracture resistance
      from those placed in dovetail preparations. On fracture loading, resin-modified
      glass ionomer restorations placed in box-only preparations were more likely to
      show adhesive failure than those placed in dovetail preparations.

PMID- 14733467
TI  - Reporting of child abuse: a follow-up survey of Texas dentists.
AB  - PURPOSE: Child abuse is a disturbingly common finding in society today. There
      have been substantial and significant increases in the incidence of child abuse
      since the last national incidence study was conducted in 1986. Kassebaum first
      reported the under-reporting of child abuse by Texas dental professionals in a
      survey in 1986. The objective of the current study was twofold: (1) assess the
      level of knowledge and attitudes among dental professionals on the important
      issue of child abuse; (2) evaluate and compare the results of the current study
      with a similar survey conducted in 1986. METHODS: A 24-question survey similar in
      format and content to the 1986 questionnaire was mailed to 1,046 Texas dentists,
      randomly selected from a membership roster provided by the Texas Dental
      Association. Both general dentists and selected specialists were included in the
      study group. The questionnaire consisted of multiple-choice and dichotomous
      yes/no questions. RESULTS: There were 383 responses to the questionnaire,
      yielding a response rate of 38%. The majority (N=289) of the respondents were
      general dentists. In answering questions about suspected and reported cases of
      child abuse, nearly 50% of the responding dentists reported they had suspected at
      least 1 case of child abuse. In the 1986 study, only 36% of the responding
      dentists reported they had suspected at least 1 case of child abuse. Between 1986
      and 2001, the survey has shown that the percentage of dentists who reported at
      least 1 case to authorities slightly increased from 19% in 1986 to 25% in 2001,
      but the ratio of suspected to reported cases had not changed since 1986.
      CONCLUSIONS: Although the composite percentage of suspecting and reporting cases
      of child abuse from this survey is higher than the percentage demonstrated in
      1986 study, there was no significant change in the relative ratio of reported
      cases to suspected cases in both surveys. This indicates that under-reporting of
      child abuse cases is still a significant problem in the dental profession in
      Texas.

PMID- 14733468
TI  - Reasons for repeat dental treatment under general anesthesia for the healthy
      child.
AB  - PURPOSE: This study investigated reasons a healthy child may need repeat dental
      treatment under general anesthesia (GA). METHODS: Experimental subjects were 23
      healthy children who received dental treatment under GA twice; controls were 23
      healthy children requiring a single dental treatment session under GA. Records
      review determined demographics, intraoperative information, diagnosis, and
      treatment provided. Parents of 11 subjects and 9 controls competed a
      questionnaire and were interviewed. RESULTS: Many factors differed between
      subject and control children. Common characteristics of children requiring repeat
      care under GA (subjects) were: (1) 100% percent caries involvement of maxillary
      central incisors at time of initial treatment; (2) majority of central incisors
      were nonrestorable; (3) still using nursing bottle at the time of GA; (4) child
      responsible for brushing own teeth; (5) poor cooperation in the medical and
      dental setting; (6) difficult personality as described by parent; (7)
      dysfunctional social situation; and (8) lack of follow-up dental care. Stainless
      steel crowns were the most successful restoration placed. CONCLUSIONS: A number
      of predictors were found to help identify high-risk children. Best outcomes
      following dental rehabilitation under GA may result from aggressive treatment of
      caries, active follow-up, and education of parents.

PMID- 14733469
TI  - Evaluation of halitosis in children and mothers.
AB  - PURPOSE: The purpose of this study was to investigate the occurrence and clinical
      parameters that are associated with halitosis in pediatric dental patients and
      compare these findings with those found for the patients' mother. METHODS:
      Children aged 5 to 12 years old were evaluated with mothers present during a
      dental visit. Each mother completed the child's medical history and a breath odor
      questionnaire. The mother and an oral breath judge (OBJ) evaluated the child's
      oral breath using organoleptic methods. A commercial breath analyzer (CBA)
      measured the oral and nasal levels of volatile sulfur compounds (VSCs) for child
      and mother before and after tongue debridement. A number of oral parameters were
      recorded for the children. RESULTS: Thirty children (mean age=8.8 years) and 18
      mothers participated. Halitosis (VSC>100 parts per billion, or ppb) was found in
      23% of children and 11% of mothers, but was not significantly correlated. In
      contrast, 61% of mothers reported halitosis in themselves and their child.
      Significant differences were found between VSC levels and frequency of tooth
      brushing (P<.05, univariate ANOVA). There was significant correlation in the
      detection of breath odor between mother and OBJ (P<.05, Pearson); however, there
      was no significant correlation between evaluators and CBA. A positive correlation
      existed between the presence of interproximal restorations and breath odor by OBJ
      (P<.05, Pearson). CONCLUSIONS: Halitosis may be a problem in some healthy
      children, but it does not correlate well with mothers' breath odor or common oral
      parameters. The organoleptic and CBA results were inconsistent, suggesting
      factors other than VSCs may be associated with halitosis in children.

PMID- 14733470
TI  - Correlation between fissure discoloration, Diagnodent measurements, and caries
      depth: an in vitro study.
AB  - PURPOSE: This in vitro study was performed to correlate the presence of
      discoloration on occlusal surfaces with its histological depth and assess its
      influence on Diagnodent measurements in a group of permanent and primary teeth.
      METHODS: Ninty-five primary and 95 permanent third molars were randomly selected
      from a pool of macroscopically intact teeth. One site of the fissure on each
      occlusal surface was selected and categorized according to its discoloration.
      Each site was measured 3 times with Diagnodent. The teeth were prepared
      histologically and evaluated according to their caries extent under a microscope
      (final magnification x 12.8). RESULTS: In the group of permanent teeth with dark
      brown or black discoloration (N=23), 13% showed dentinal caries, 57% were sound
      or had an initial enamel lesion, and 30% had a deep enamel lesion. In the group
      of primary teeth with dark brown and black discoloration (N=19), 42% presented
      dentinal caries, 42% showed deep enamel caries, and 16% had an initial enamel
      lesion. The difference between permanent and primary teeth was statistically
      significant (P<.05). Discolored fissures showed higher Diagnodent values than
      nondiscolored or opaque fissures in both groups (independent of their caries
      status). CONCLUSIONS: The presence of brown or dark spots on fissures were not
      useful for the prediction of dentinal caries for permanent teeth. In primary
      teeth, however, a higher correlation between fissure discoloration and dentinal
      lesions was found. Diagnodent tends to overscore discolored surfaces.

PMID- 14733472
TI  - Restorative cost savings related to dental sealants in Alabama Medicaid children.
AB  - PURPOSE: Since properly placed and retained sealants can reduce the incidence of
      caries lesions and save subsequent restorative costs, the purpose of this study
      was to compare the subsequent restorative cost in a group of predominantly
      African American Medicaid children who received prior sealants to that of a group
      of children who did not receive sealants. METHODS: Dental claims of 2 cohorts of
      5- to 7-year-old children who were continuously enrolled in Alabama Medicaid from
      1990 to 1997 (N=9,549) and who either did or did not receive sealants were
      analyzed using basic descriptive statistics, chi-square and t tests, and
      regression analysis. The subsequent restorative care costs related to 1-surface
      posterior amalgam or resin restorations were evaluated in relation to sealant
      status and selected independent variables. RESULTS: Only 10% of the children with
      at least 1 prior sealant claim obtained subsequent 1-surface posterior amalgam or
      resin restorations. This proportion was 33% among children without a prior
      sealant claim (OR=4.2, 95% CI=3.6-4.9). On average, total Medicaid reimbursement
      per child for sealants, plus subsequent restorative care was 56 dollars in the
      sealant group compared to 72 dollars for subsequent care alone in the nonsealant
      group. This difference was independent of the child's race, gender, or age.
      CONCLUSIONS: As expected, children who do not receive sealants are more likely to
      obtain subsequent restorative care and cost more money to the health care system.
      However, the modest sealant-related subsequent restorative cost savings observed
      among Alabama Medicaid children may be an underestimate of the real cost-benefits
      of sealants.

PMID- 14733471
TI  - Dental visits and professional fluoride applications for children ages 3 to 6 in
      Iowa.
AB  - PURPOSE: The purpose of this study was to report the occurrence of having a
      dental visit and/or a topical fluoride treatment from age 36 months to 72 months
      among a cohort of children followed longitudinally since birth. METHODS: Families
      of children enrolled in a study of fluoride ingestion were asked about their
      children's dental appointments and office fluoride treatments occurring during
      the time interval since the previous mailed questionnaire. Percentages of
      children who had at least 1 dental visit and at least 1 fluoride treatment during
      each 6-month period, each year of life, and cumulatively from birth were
      calculated separately. Factors related to dental visits were assessed using
      generalized linear models. RESULTS: Among those with complete data, 71% reported
      a visit cumulatively from birth to 48 months, 89% from birth to 60 months, and
      96% by age 72 months. Similarly, 27% reported a professional fluoride treatment
      by 48 months, 44% by 60 months, and 66% by 72 months. CONCLUSIONS: Among children
      who had not been seen by a dentist by age 3, almost all were seen by age 6.
      Similarly, among those who had no professional fluoride treatment by age 3,
      almost two-thirds received one by age 6.

PMID- 14733473
TI  - The clinical and radiographic success of bonded resin composite strip crowns for
      primary incisors.
AB  - PURPOSE: The aim of this study was to examine the clinical and radiographic
      success of the treatment of maxillary anterior primary incisors with composite
      resin strip crowns placed in a private practice setting. METHODS: This was a
      retrospective, clinical study of patients who had strip crowns (SC) placed on
      maxillary primary incisors, returned for at least 1, 6-month recall examination,
      and whose parents consented to participate in the study. Radiographic and
      photographic examinations were used for evaluation. Two evaluators rated the
      images independently. When ratings were not in agreement, the 2 examiners
      reviewed the photograph or radiograph together and reached a consensus rating.
      RESULTS: One hundred twelve restorations placed in 40 children were evaluated.
      The evaluations were performed after the crowns had been in place for an average
      of 18 months. None of the restorations were totally lost, and only 12% were rated
      as having lost some resin material, resulting in an 88% overall retention rate.
      There was no difference in restoration success if the crowns were placed 4 at a
      time, or if fewer crowns were placed in a single sitting; the failure rates were
      comparable. Teeth that had pulpal treatment were judged to have far more
      significant color match discrepancies than those teeth without pulpal treatment.
      Ninety-one percent of the teeth demonstrated healthy pulps. Eight percent had
      some pulpal changes but did not require immediate attention. Only 1 tooth showed
      radiographic evidence of pulpal necrosis. Only 11 teeth had pulpal treatment, but
      of these, 10 demonstrated clinical success. CONCLUSIONS: Composite resin strip
      crowns for restoring primary incisors with large or multisurface caries performed
      well. Color match of these crowns with adjacent teeth may be significantly
      reduced when placed upon teeth that have undergone pulpectomy treatment and have
      been obturated with an iodoform paste. However, based upon the results of this
      study, the strip crown may provide an esthetic and durable restoration for
      carious primary incisors.

PMID- 14733474
TI  - Long-term clinical performance of esthetic primary molar crowns.
AB  - PURPOSE: The aim of the study was to report the long-term clinical performance of
      esthetic primary molar crowns and compare them to that of stainless steel crowns
      (SSC). METHODS: Twenty crowns (10 conventional and 10 esthetic) placed in 10
      children who had participated in a previously reported study, were assessed again
      after 4 years. The crowns were evaluated clinically and radiographically
      according to the following parameters: gingival health, marginal extension, crown
      adequacy, proper occlusion, proximal contact, chipping of the facing (for
      esthetic crowns only), and cement removal. RESULTS: At the 4 year evaluation, all
      the esthetic crowns showed chipping of the facing. No difference was found for
      marginal extension, occlusion, crown adequacy and periodontal health between SSCs
      and the esthetic crowns. CONCLUSIONS: After 4 years, all the esthetic crowns
      presented chipping of the facing and, consequently, a very poor esthetic
      appearance.

PMID- 14733475
TI  - Reshaping a mesiodens.
AB  - A mesiodens is a supernumerary tooth that is found in the midline of the maxilla.
      Fifteen percent erupt usually between the ages of 3 and 7. The standard treatment
      is extraction of the supernumerary to allow the permanent incisors to erupt
      properly. This case report describes an instance where the primary incisor was
      prematurely exfoliated due to the eruption of the mesiodens. Because of the
      favorable position of the mesiodens in the dental arch, it was decided to reshape
      the supernumerary to resemble a primary incisor. This was accomplished
      successfully, and the mesiodens is being monitored to assess any need to trim or
      add to the bonding material as the child grows.

PMID- 14733476
TI  - A retrospective study of the use of the Bluegrass appliance in the cessation of
      thumb habits.
AB  - PURPOSE: The purpose of this study was to evaluate the use of the Bluegrass
      appliance in ceasing the thumb-sucking habit. METHODS: Patient records of 41
      subjects, ages 4 to 20 years of age, who attended the University of Kentucky
      Pediatric Dental Clinic for the treatment of a thumb-sucking habit with the
      Bluegrass appliance, were reviewed. Of the 41 subjects, 30 were included in the
      study. Data collected from the records included age, sex, past dental history,
      past medical history, history during treatment with the Bluegrass appliance,
      patient and/or parental/legal guardian report of cessation of the habit, and
      total treatment time. RESULTS: Of the 30 subjects included in the study, the
      results showed that in 28 (93%) of the patients, the thumb habit was ceased after
      insertion of and complete treatment with the Bluegrass appliance. The average
      reported treatment time for the cessation of the habit was 12.3 weeks+/-12.2
      weeks. The mean total treatment time for the thumb habit with the Bluegrass
      appliance was 30.3 weeks+/-1 7.7 weeks, with 6 (20%) of the patients requiring
      reinsertion of the appliance during treatment. CONCLUSIONS: The results of this
      study suggest that the Bluegrass appliance is an effective treatment option for
      the cessation of a thumb-sucking habit with limited treatment complications.

PMID- 14733477
TI  - Lingual epidermoid cyst: case report in an infant.
AB  - The purpose of this article was to present a rare case of epidermoid cyst on the
      ventral region of the tongue in a 15-month-old child. During clinical
      examination, a sessile, yellowish lesion measuring approximately 0.5 cm was
      noticed. The lesion had existed since the child's birth and was causing
      discomfort due to friction of the tongue against the alveolar ridge during
      mastication. The chosen treatment was total removal of the lesion. The
      histopathological findings confirm the diagnosis of an epidermoid cyst,
      characterized by the presence of: (1) a cyst cavity lined by stratified squamous
      epithelium with keratinization on the surface; and (2) connective tissue with a
      mild inflammation. The proposed treatment was considered successful as the case
      was solved and there was no recurrence.

PMID- 14733478
TI  - Early childhood caries lesions in preschool children in Kerala, India.
AB  - PURPOSE: No data are available on possible risk indicators or the prevalence of
      caries lesions for preschool children under 4 years of age in Kerala, southern
      India. Therefore, the aims of this study were: (1) to gather data on caries
      lesion frequency and distribution; (2) to determine any possible associations
      with feeding habits and oral health care practices. METHODS: A sample of 530
      children, aged from 8 to 48 months (mean=2.5+/-0.96 years), who attended 13 day
      care centers were clinically examined for caries lesions using a disposable mouth
      mirror, tongue spatula, and a torch light. There were 513 dentate children. The
      caregiver of each child then completed, by interview, a structured questionnaire.
      RESULTS: Among the group of 252 girls and 278 boys, the dmft was 1.84+/-2.87 with
      56% of the children being caries-lesion free. Fifty-nine (12%) were considered to
      have early childhood caries (ECC), based on the criteria that smooth surface
      caries lesions on all 4 maxillary incisor teeth indicated severe ECC. Breast
      feeding was practiced by 99% of the mothers, and 5% did so exclusively.
      Generally, breast-feeding was on demand. Statistically significant correlations
      were found between caries lesions and the child's dental condition, as perceived
      by the mother or caregiver (P<.0001), the dental status of the caregiver
      (P=.0417), consumption of snacks (P=.0177), giving of sweets as a reward
      (P<.0001), cleaning of the child's mouth (P<.0001), oral hygiene status of the
      child (P<.0001) and low socioeconomic status, as measured by income (P<.0001).
      CONCLUSION: From the results of this study of preschool children in Kerala, the
      groups at high risk from dental caries lesions are: (1) those with poor oral
      hygiene status; (2) those who consume snacks and are given sweets as rewards; (3)
      those belonging to a lower socioeconomic class.

PMID- 14733479
TI  - The effect of chemotherapy in pregnant women on the teeth of offspring.
AB  - No standardized therapeutic interventions have been reported for patients
      diagnosed with breast cancer during pregnancy. A high risk for malformations in
      the fetus has been claimed when chemotherapy is administered during the first
      trimester of the pregnancy. Tooth formation of the primary teeth begins at 11 to
      14 weeks of fetal life and is completed postnatally. Therefore, the teeth may be
      affected by insults during the second and third trimesters of pregnancy, thus
      acting as a sensitive parameter of possible placental transfer of chemotherapy.
      The cases presented describe the dental status of 2 young children whose mothers
      received chemotherapy for cancer during the third trimester of their pregnancies
      (adriamycin or adriamycin and cytoxan). Both women gave birth to healthy babies,
      born with full hair, normal blood counts, and birth weights (3.200 and 3.100
      kgs). Dental examinations of both children (at ages 18 and 30 months) revealed
      sound teeth. It seems that adriamycin and cytoxan for cancer chemotherapy do not
      affect the primary teeth when administered in the third trimester of pregnancy.

PMID- 14733480
TI  - Domestic pigeons (Columba livia) discriminate between photographs of individual
      pigeons.
AB  - In two experiments, we examined the discrimination of photographs of individual
      pigeons by pigeons, using go/no-go discrimination procedures. In Experiments 1A
      and 1B, the pigeons were trained to discriminate 4 photographs of one pigeon from
      those of a number of pigeons. The subjects learned the discrimination, but their
      discriminative behavior did not transfer to new photographs taken from novel
      perspectives. When the pigeons were trained to discriminate between 20
      photographs of five pigeons taken from four perspectives as the S+ and 20
      photographs of five different pigeons as the S-, the subjects learned the
      discrimination, and this discriminative behavior partially transferred to new
      photographs taken from novel perspectives (Experiments 2A-2C). The results
      suggest that pigeons are able to discriminate among conspecific individuals,
      using stationary visual cues. This strengthens the assumption in evolutionary
      theory that animals can discriminate among individuals and encourages further
      investigation as to how this ability is used in various behaviors of animals.

PMID- 14733481
TI  - Learning by pigeons playing against tit-for-tat in an operant prisoner's dilemma.
AB  - Each of four pigeons was exposed to a single random-ratio schedule of
      reinforcement in which the probability of reinforcement for a peck on either of
      two keys was 1/25. Reinforcer amounts were determined by an iterated prisoner's
      dilemma (IPD) matrix in which the "other player" (a computer) played tit-for-tat.
      One key served as the cooperation (C) key; the other served as the defection (D)
      key. If a peck was scheduled to be reinforced and the D-key was pecked, the
      immediate reinforcer of that peck was always higher than it would have been had
      the C-key been pecked. However, if the C-key was pecked and the following peck
      was scheduled to be reinforced, reinforcement amount for pecks on either key were
      higher than they would have been if the previous peck had been on the D-key.
      Although immediate reinforcement was always higher for D-pecks, the overall
      reinforcement rate increased linearly with the proportion of C-pecks. C-pecks
      thus constituted a form of self-control. All the pigeons initially defected with
      this procedure. However, when feedback signals were introduced that indicated
      which key had last been pecked, cooperation (relative rate of C-pecks)--hence,
      self-control--increased for all the pigeons.

PMID- 14733482
TI  - Response stability and variability induced in humans by different feedback
      contingencies.
AB  - In two experiments, the behavioral effects of different response-feedback
      contingencies were examined with a task requiring human subjects to repeatedly
      type three-key sequences on a computer keyboard. In Experiment 1, the subjects
      first received positive feedback for response variability, followed by no
      feedback, or vice versa In Experiment 2, the subjects first received positive
      feedback for response variability, followed by response-independent positive
      feedback, or vice versa. Response stability and variability were examined using
      different measures, such as percentage of trials meeting the variability
      criteria, frequency of use of the different response alternatives, and
      autocorrelations as an index of response randomness. The subjects' behavior in
      the first phase in each condition came to reflect the current feedback
      contingency. Depending on the measure examined, responding after each contingency
      change was characterized by both response stability and decreases or increases in
      response variability. The collective results are discussed in the framework of
      previous animal and human studies on behavioral stability and variability.

PMID- 14733483
TI  - Exploring the limits of spatial memory in rats, using very large mazes.
AB  - In Experiment 1, rats foraged for food in six successive phases with 8, 16, 24,
      32, 40, and 48 arms attached in random locations to a large radial maze. The
      percentage of novel choices appeared to be determined more by spatial proximity
      than by number of arms. In Experiment 2, rats foraged for food in four successive
      phases with 8, 16, 24, and 48 arms attached to the maze in spread-out or tight
      configurations. Performance was poor in the tight configurations regardless of
      the number of arms. Performance was excellent in the 8-arm spread-out condition
      but declined as 16 and, then again, 24 arms were added. Thus, spatial separation,
      not number of locations, was the chief determinant of performance in the first
      two experiments. In Experiment 3, in successive phases, 8, 16, 24, 32, 40, 48,
      16, and 8 food towers were set in a circle on the floor, with the spatial
      separation between adjacent towers held constant at 33 cm. The percentage of
      novel choices declined as 8 towers became 16 and did not change again with 24,
      32, 40, or 48 towers in place but then increased again as 16 towers became 8. In
      Experiment 4, in successive phases, 8, 16, 24, and 32 food towers were set in a
      circle, with the spatial separation between adjacent towers held constant at 66
      cm. The percentage of novel choices declined as 8 towers became 16 and again as
      16 towers became 24 but did not decline further. These data were discussed in
      terms of the fundamental problems posed by variations in the number of food
      locations in the pursuit of the limit of spatial memory in rats.

PMID- 14733485
TI  - Massive preexposure and preexposure in multiple contexts attenuate the context
      specificity of latent inhibition.
AB  - Latent inhibition, which refers to attenuated responding to a conditioned
      stimulus (CS) after CS-unconditioned stimulus (CS-US) pairings as a result of CS
      alone presentations prior to the pairings, is often attenuated if preexposure and
      conditioning occur in different contexts (i.e., it is context specific). Here we
      report two conditioned lick suppression experiments, using rat subjects, that
      examined whether manipulations known to attenuate the context specificity of
      extinction could also eliminate the context specificity of latent inhibition.
      Context specificity of latent inhibition was eliminated when the CS was
      preexposed in multiple contexts (Experiment 1) and when the CS was massively pre
      exposed in the training context alone (Experiment 2). These results and their
      practical implications are discussed in the framework of contemporary theories of
      latent inhibition.

PMID- 14733484
TI  - Effects of context exposure during conditioning on conditioned taste aversions.
AB  - Rats were used in a conditioned taste aversion procedure in order to examine the
      effects of context exposure duration during the conditioning sessions on
      conditioned responding. One flavor was paired with lithium chloride during a long
      session in one context, whereas another flavor was conditioned during a short
      session in another context. Testing occurred in the home cage. The results showed
      that conditioning during short sessions produced strong conditioned taste
      aversions. Conditioning during long sessions produced strong conditioned taste
      aversions when the conditioned-stimulus-unconditioned-stimulus (CS-US) pairing
      occurred at the end of the lengthy session. Other results showed that context-US
      associations were formed during the short duration sessions and that these
      associations supported conditioned responding to the CS trained in that context.
      The results are discussed with respect to the different influences that
      contextual cues can exert on conditioned responding.

PMID- 14733486
TI  - Appetitive latent inhibition in rats: now you see it (sign tracking), now you
      don't (goal tracking).
AB  - Latent inhibition (LI), the retardation of Pavlovian acquisition after
      nonreinforced preexposure to the conditioned stimulus, is a popular paradigm for
      studying basic attentional and memory processes from both behavioral and
      neurobiological perspectives. It is argued that whether LI emerges depends on the
      behavioral measure used to index conditioning. An experiment with rats
      demonstrates that stimulus preexposure retards the development of sign-tracking
      responses directed at the stimulus, but not the development of goal-tracking
      responses directed at the site of food delivery. These results are consistent
      with models that explain LI in terms of a deficit in retrieval.

PMID- 14733487
TI  - Outcome-specific conditioned inhibition in Pavlovian backward conditioning.
AB  - In the present experiments, the outcome specificity of learning was explored in
      an appetitive Pavlovian backward conditioning procedure with rats. The rats
      initially were administered Pavlovian backward training with two qualitatively
      different unconditioned stimulus conditioned-stimulus (US-CS) pairs of stimuli
      (e.g., pellet --> noise or sucrose --> light), and then the effects of this
      training were assessed in Pavlovian-to-instrumental transfer (Experiment 1) and
      retardation-of-learning (Experiment 2) tests. In the transfer test, it was shown
      that during the last 10-sec interval, the CSs selectively reduced the rate of the
      instrumental responses with which they shared a US, relative to the instrumental
      responses with which they did not share a US. The opposite result was obtained
      when the USs (in the absence of the CSs) were presented noncontingently. In the
      retardation test, conditioned magazine approach, responding to the CSs was
      acquired more slowly when the stimulus-outcome combinations in the backward and
      the forward conditioning phases were the same, as compared with when they were
      reversed. These results are collectively in accord with the view that Pavlovian
      backward conditioning can result in the formation of outcome-specific inhibitory
      associations. Alternative views of backward conditioning are also examined.

PMID- 14733488
TI  - Determination of phenolic constituents of biological interest in red wine by
      capillary electrophoresis with electrochemical detection.
AB  - A simultaneous determination of trans-resveratrol, (-)-epicatechin, and (+)
      catechin in red wine by capillary electrophoresis with electrochemical detection
      (CE-ED) is reported. The effects of the potential of the working electrode, pH
      and concentration of running buffer, separation voltage, and injection time on CE
      ED were investigated. Under the optimum conditions, the analytes could be
      separated in a 100 mmol/L borate buffer (pH 9.2) within 20 min. A 300 microm
      diameter carbon disk electrode has a good response at +0.85 V (vs SCE) for all
      analytes. The response was linear over 3 orders of magnitude with detection limit
      (S/N = 3) ranging from 2 x 10(-7) to 5 x 10(-7) g/mL for all analytes. This
      method has been used for the determination of these analytes in red wine without
      enrichment, and the assay result was satisfactory.

PMID- 14733489
TI  - Kinetics of diglyceride formation and isomerization in virgin olive oils by
      employing 31P NMR spectroscopy. Formulation of a quantitative measure to assess
      olive oil storage history.
AB  - Diacylglycerol isomers and free acidity were determined for five extra virgin
      olive oils of different initial acidities by employing a facile (31)P NMR
      methodology as a function of storage time and storage conditions. The kinetic
      treatment of the hydrolysis of triacylglycerols (TGs) and the isomerization of
      1,2-diacylglycerols (1,2-DGs) to 1,3-diacylglycerols (1,3-DGs) during storage of
      18 months at ambient temperature in the dark and light and at 5 degrees C in the
      dark showed that the isomerization is strongly dependent on the rate of the TGs
      hydrolysis, the initial free acidity (H(0)) of the virgin olive oil samples, and
      storage conditions. Although the time-evolution of the diacylglycerols (DGs)
      depends on the TGs hydrolysis, the ratio D of the concentration of 1,2-DGs to the
      total amount of DGs was found to be independent of this factor. From the kinetic
      expression of the ratio D, a quantitative measure was formulated that allows the
      estimation of the storage time or age of virgin olive oils. Application of this
      quantitative measure to several olive oil samples of known and unknown storage
      history resulted in a very good agreement with respect to the actual storage time
      for up to 10-12 months of storage. For a longer storage period, where the
      isomerization of DGs is close to its equilibrium state, the calculated age index
      is only indicative.

PMID- 14733490
TI  - Magnetic resonance imaging for nondestructive analysis of wine grapes.
AB  - Magnetic resonance imaging (MRI) was used to study the growth and ripening of
      grape berries for three varieties. The results show that this technique allows
      the visualization of internal characteristics of berries using noninvasive
      procedures in order to obtain the volume and degrees Brix distribution within a
      cluster. Samples of Cabernet Sauvignon, Carmenere, and Chardonnay varieties
      collected over the 2002 season were analyzed. Calibration models were developed
      to correlate soluble solids (degrees Brix) against spin-lattice relaxation time
      t(1) and spin-spin relaxation time t(2). The correlation of degrees Brix and t(1)
      was R(2) = 0.75 for Cabernet Sauvignon, R(2) = 0.8 for Carmenere, and R(2) = 0.65
      for Chardonnay. In the case of t(2) the correlation was significantly lower.
      Reconstruction techniques for the three-dimensional representation of clusters
      were developed, allowing an interactive visualization of the bunches. The method
      also provides volume measurements of single berries and their distribution within
      the cluster with an accuracy of 3% and R(2) = 0.98. These results show the
      potential of MRI in the wine industry for both monitoring and research. Not only
      does it provide quantitative information about the berries such as volume and
      degrees Brix distributions, but it can also be used to support the sampling
      procedures by providing a better cluster characterization.

PMID- 14733491
TI  - Determination of five macrolide antibiotic residues in honey by LC-ESI-MS and LC
      ESI-MS/MS.
AB  - Liquid chromatography-electrospray ionization mass spectrometry methods (LC-ESI
      MS and LC-ESI-MS/MS) for the determination of five macrolide antibiotics
      including spiramycin, tilmicosin, oleandomycin, erythromycin, and tylosin in
      honey are presented. Macrolides were protonated to form singly and/or doubly
      charged pseudomolecular ions, depending on their chemical structures, in an
      electrospray positive ionization mode. Data acquisition under MS/MS was achieved
      by applying multiple reaction monitoring (MRM) of two or three fragment ion
      transitions to provide a high degree of sensitivity and specificity. The
      recoveries, that is, determined by LC-ESI-MS/MS, of the five macrolides at
      fortified levels of 6, 16, 40, and 80 microg/kg ranged from 75.5 to 135.7% in
      light honey and from 42.1 to 111.0% in dark honey. The ion ratios obtained under
      MS/MS were key criteria to confirm the identity of macrolides in incurred
      samples. LC-ESI-MS/MS method detection limits of the five macrolides were <0.1
      microg/kg.

PMID- 14733492
TI  - Robust and sensitive monoclonal enzyme-linked immunosorbent assay for the
      herbicide molinate.
AB  - This paper reports on the generation of monoclonal antibodies and the development
      of a new enzyme-linked immunosorbent assay (ELISA) for the detection of molinate
      (S-ethyl hexahydroazepine-1-carbothioate). Hybridoma cells were generated using
      spleen and lymph node cells from a mouse immunized with S-2-carboxyethyl
      hexahydroazepine-1-carbothioate conjugated to keyhole limpet hemocyanin. After
      screening with a competitive ELISA, two monoclonal antibodies, mAbs 16C11 and
      14D7, with IC(50) values of 82 +/- 2 and 173 +/- 8 ng/mL, respectively, were
      selected. MAb 16C11 can detect molinate concentrations of 1 ng/mL with no cross
      reactivity to any other thiocarbamate pesticides; however, it was susceptible to
      the presence of organic solvents and to variation in buffer ionic strength. MAb
      14D7 tolerated concentrations up to 5% of propylene glycol and 12.5% of
      acetonitrile in the assay buffer. The sensitivity of mAb 14D7 was further
      improved by decreasing the amount of coating antigen in the ELISA; the final
      inhibition assay showed an IC(50) of 69.2 +/- 1.4 ng/mL. In summary, mAb14D7
      provided a more sensitive and robust assay, as compared with previous polyclonal
      antibody-based assays, with the additional advantage of being based upon a
      consistent and unlimited source of a defined reagent.

PMID- 14733493
TI  - Characterization of flavonols in cranberry (Vaccinium macrocarpon) powder.
AB  - Flavonoids were extracted from cranberry powder with acetone and ethyl acetate
      and subsequently fractionated with Sephadex LH-20 column chromatography. The
      fraction eluted with a 60% methanol solution was composed primarily of phenolic
      constituents with maximum absorbance at 340 nm. A high-performance liquid
      chromatography procedure was developed, which resolved 22 distinct peaks with
      UV/vis and mass spectra corresponding to flavonol glycoside conjugates. Six new
      constituents not previously reported in cranberry or in cranberry products were
      determined through NMR spectroscopy to be myricetin-3-beta-xylopyranoside,
      quercetin-3-beta-glucoside, quercetin-3-alpha-arabinopyranoside, 3'
      methoxyquercetin-3-alpha-xylopyranoside, quercetin-3-O-(6' '-p-coumaroyl)-beta
      galactoside, and quercetin-3-O-(6' '-benzoyl)-beta-galactoside. Quercetin-3-O-(6'
      '-p-coumaroyl)-beta-galactoside and quercetin-3-O-(6' '-benzoyl)-beta-galactoside
      represent a new class of cranberry flavonol compounds with three conjugated
      components consisting of a flavonol, sugar, and carboxylic acid (benzoic or
      hydroxycinnamic acids). This is also the first report identifying quercetin-3
      arabinoside in both furanose and pyranose forms in cranberry. Elucidation of
      specific flavonol glycosides in cranberry is significant since the specificity of
      the sugar moiety may play a role in the bioavailability of the flavonol
      glycosides in vivo.

PMID- 14733494
TI  - Liquid chromatographic determination of fumonisins B1, B2, and B3 in corn silage.
AB  - Corn silage was dried, ground, and then extracted with 0.1 M
      ethylenediaminetetraacetic acid. The filtrate was applied to a FumoniTest
      immunoaffinity column. Fumonisins were derivatized with naphthalene-2,3
      dicarboxaldehyde, separated on a C(18) liquid chromatographic column, and
      detected by fluorescence. The detection limits for fumonisin B(1), fumonisin
      B(2), and fumonisin B(3) were 50, 25, and 25 ng/g of dried silage, respectively.
      Recoveries of fumonisin B(1), fumonisin B(2), and fumonisin B(3) from wet and
      dried corn silage spiked over the range of 100-5000 ng/g averaged 91-106%. The
      method was applied to corn silage samples collected from the midwestern area of
      the United States during 2001-2002. Of 89 corn silage samples, fumonisin B(1),
      fumonisin B(2), and fumonisin B(3) were found in 86 (97%), 64 (72%), and 51 (57%)
      of the samples. The mean positive levels of fumonisin B(1), fumonisin B(2), and
      fumonisin B(3) were 615, 93, and 51 ng/g, respectively, in dried silage. This
      suggests that fumonisins may be frequent low level contaminants in corn silage.

PMID- 14733495
TI  - Detection of apple juice concentrate in the manufacture of natural and sparkling
      cider by means of HPLC chemometric sugar analyses.
AB  - An HPLC method for sugar analyses in cider was used in order to detect the
      presence of apple juice concentrate. Sugars, previously derivatized with p
      aminobenzoic ethyl ester, were analyzed by reversed-phase liquid chromatography
      using a C(8) column and a mobile phase of citrate buffer pH
      5.5/tetrahydrofuran/acetonitrile, operated in gradient mode. The use of this
      analytical procedure together with chemometric techniques, such as principal
      component analysis and Bayesean analysis, allowed the authors to establish the
      minimum concentration of apple juice concentrate obtained by liquefaction or
      press technology that can be detected in natural cider.

PMID- 14733496
TI  - Detection and quantification of apple adulteration in diluted and sulfited
      strawberry and raspberry purees using visible and near-infrared spectroscopy.
AB  - Adulteration of sulfited strawberry and raspberry purees by apple is a commercial
      problem. Strawberry (n = 31) and raspberry (n = 30) purees were prepared from
      Irish-grown fruit and adulterated at levels of 10-75% w/w using cooking apples.
      Visible and near-infrared transflectance spectra were recorded using a 0.1 mm
      sample thickness. Classification and quantification models were developed using
      raw and scatter-corrected and/or derivatized spectral data. Classification as
      pure strawberry or raspberry was attempted using soft independent modeling of
      class analogy. The best models used spectral data in the wavelength ranges 400
      1098 nm (strawberry) and 750-1098 nm (raspberry) and produced total correct
      classification rates of 75% (strawberry) and 95% (raspberry). Quantification of
      apple content was performed using partial least-squares regression. Lowest
      predictive errors obtained were 11.3% (raspberry) and 9.0% (strawberry). These
      results were obtained using spectral data in the wavelength ranges 400-1880 and
      1100-1880 nm, respectively. These results suggest minimum detection levels of
      apple in soft fruit purees of approximately 25 and 20% w/w for raspberry and
      strawberry, respectively.

PMID- 14733497
TI  - Quantitative high-performance liquid chromatography analyses of flavonoids in
      Australian Eucalyptus honeys.
AB  - Flavonoids of nine Australian monofloral Eucalyptus honeys have been analyzed and
      related to their botanical origins. The mean content of total flavonoids varied
      from 1.90 mg/100 g of honey for stringybark (E. globoidia) honey to 8.15 mg/100 g
      of honey for narrow-leaved ironbark (E. crebra) honey, suggesting that species
      specific differences occur quantitatively among these Eucalyptus honeys. All of
      the honey samples analyzed in this study have a common flavonoid profile
      comprising tricetin (5,7,3',4',5'-pentahydroxyflavone), quercetin (3,5,7,3',4'
      pentahydroxyflavone), and luteolin (5,7,3',4'-tetrahydroxyflavone), which,
      together with myricetin (3,5,7,3',4',5'-hexahydroxyflavone) and kaempferol
      (3,5,7,4'-tetrahydroxyflavone), were previously suggested as floral markers for
      European Eucalyptus honeys. Thus, flavonoid analysis could be used as an
      objective method for the authentication of the botanical origin of Eucalyptus
      honeys. Moreover, species-specific differences can also be found in the
      composition of honey flavonoid profiles. Among these honeys, bloodwood (E.
      intermedia) honey contains myricetin and tricetin as the main flavonoid
      compounds, whereas there is no myricetin detected in yapunyah (E. ochrophloia),
      narrow-leaved ironbark (E. crebra), and black box (E. largiflorens) honeys.
      Instead, these types of Eucalyptus honeys may contain tricetin, quercetin, and/or
      luteolin as their main flavonoid compounds. Compared to honeys from other
      geographical origins, the absence or minor presence of propolis-derived
      flavonoids such as pinobanksin, pinocembrin, and chrysin in Australian honeys is
      significant. In conclusion, these results demonstrate that a common flavonoid
      profile exists for all of the Eucalyptus honeys, regardless of their geographical
      origins; the individual species-specific floral types of Eucalyptus honey so
      common in Australia could be possibly differentiated by their flavonoid profile
      differences, either qualitatively or quantitatively or both.

PMID- 14733498
TI  - Solid-state 15N NMR studies of tobacco leaves.
AB  - Nitrogen-containing compounds are one important class of constituents in tobacco
      because of various pharmacological and biological properties. Three types of
      tobacco leaves (burley, bright, and oriental) were studied using solid-state
      (15)N NMR cross polarization with magic-angle spinning, dipolar dephasing and
      five pi replicated magic angle turning (FIREMAT) experiments. The results show
      that burley tobacco leaves contain significantly more pyridinic nitrogen than
      that of bright or oriental tobacco leaves. The principal values of (15)N chemical
      shift tensors of nitrogen functional groups were obtained from the FIREMAT data.
      Possible assignments of solid-state (15)N NMR resonances were made using nitrogen
      chemical shift tensors in some model compounds or isotropic chemical shift values
      from liquid NMR results. To the best of our knowledge, this is the first solid
      state (15)N NMR study of tobacco plant material.

PMID- 14733499
TI  - GC-MS determination of flavonoids and phenolic and benzoic acids in human plasma
      after consumption of cranberry juice.
AB  - A GC-MS method was developed for the determination of various flavonoids and
      phenolic and benzoic acids in human plasma. The procedure involved the extraction
      of flavonoids and phenolic and benzoic acids with ethyl acetate, followed by the
      derivatization of the phenolic and benzoic compounds with BSTFA (N,O
      bis(trimethylsilyl) trifluoroacetamide) + TMCS (trimethylchlorosilane) reagent.
      The trimethylsilyl derivatives formed were separated and quantitated using GC-MS.
      Twenty flavonoids and phenolic and benzoic compounds have been well separated in
      the spiked human plasma without any interference. The average recovery was 79.3%.
      Several phenolic acids such as o-hydroxybenzoic, p-hydroxyphenylacetic, 2,3
      dihydroxybenzoic, 2,4-dihydroxybenzoic, ferulic, sinapic, and benzoic acid were
      identified and quantified in human plasma after consumption of a cranberry juice.
      This developed method provides a simple, specific, and sensitive technique for
      the simultaneous determination of flavonoids and phenolic and benzoic acids in
      human plasma and is suitable for bioavailability and pharmacokinetic studies.

PMID- 14733500
TI  - Insulin secretion and cyclooxygenase enzyme inhibition by cabernet sauvignon
      grape skin compounds.
AB  - Bioassay-guided isolation and purification of hexane and ethyl acetate extracts
      of Cabernet Sauvignon grape skin yielded nine compounds (1-9), which were
      identified as beta-sitosterol-6'-linolenoyl-3-O-beta-D-glucopyranoside (1), beta
      sitosterol (2), beta-sitosterol-3-O-beta-D-glucoside (3), oleanolic acid (4),
      oleanolic aldehyde (5), resveratrol (6), (+)-epsilon-viniferin (7), (-)-catechin
      (8), and 1-triacontanol (9). The structures of these compounds were established
      by spectroscopic methods. The compounds were assayed for insulin production using
      an INS-1 cell assay. In a dose-response study, compound 4 stimulated insulin
      production of INS-1 cells by 20.23, 87.97, 1.13, and 6.38 ng of insulin/mg of
      protein at 6.25, 12.5, 25, and 50 microg/mL, respectively. This trend was similar
      to the dose-dependent insulin production of INS-1 cells by glucose. Compound 5
      also showed a dose-dependent insulin production in this assay. The isolated
      compounds were also assayed for cyclooxygenase-1 and -2 (COX) enzyme inhibitory
      activities. At 100 microg/mL, compounds 2, 3, and 4 inhibited the COX-2 enzyme by
      11, 12, and 10%, respectively, but did not show activities on the COX-1 enzyme.
      Compounds 6, 7, and 8 at 100 microg/mL inhibited the COX-1 enzyme by 98, 99, and
      98%, respectively, and the COX-2 enzyme by 0, 47, and 72%, respectively. This is
      the first report of beta-sitosterol-6'-linolenoyl-3-O-beta-D-glucopyranoside (1)
      from grape skin and insulin secretion activities of compounds 4 and 5.

PMID- 14733501
TI  - Flavanol content and antioxidant activity in winery byproducts.
AB  - Proanthocyanidins, particularly those coming from wine and grape products, have
      became of interest to nutritionists. Particular attention is currently being paid
      to the exploitation of this kind of grape byproducts for obtaining bio-active
      phenolic compounds with potential application as food antioxidants and preventive
      agents against cancer and other diseases. In this work, the flavanol composition
      of various winery byproducts submitted to different degrees of industrial
      exploitation has been studied and their antioxidant activity determined using two
      different methods (TBARS and TEAC) to evaluate their interest as suitable sources
      for the preparation of flavanol-rich antioxidant extracts. All the byproducts
      studied were still good flavanol sources no matter their exploitation degree. An
      important conclusion was that dried grape seeds, obtained as an end byproduct
      after the color extraction and alcohol distillation of the wine pomace, still
      kept important flavanol concentrations and significant antioxidant activity, even
      if they were submitted to high temperatures. These byproducts can be considered a
      cheap source for the extraction of antioxidant flavanols, which can be used as
      dietary supplements or in the production of phytochemicals.

PMID- 14733502
TI  - Biological effects of epicuticular flavonoids from Primula denticulata on human
      leukemia cells.
AB  - The biological effects of epicuticular substances in farinose exudates
      accumulated on inflorescence shafts and calyces of Primula denticulata on human
      acute myeloid leukemia cells (HL-60) were analyzed. The crude material possessed
      little antioxidative capacity but strong cytostatic properties. Some of its known
      components (5-hydroxyflavone, 2'-hydroxyflavone, 5,2'-dihydroxyflavone, and 5,8
      dihydroxyflavone) were further tested to identify the biologically active
      compounds. The effects of these flavones on cell cycle progression, mitochondrial
      membrane potential, and reactive oxygen species have been investigated by flow
      cytometry. The flavonol quercetin was included in the study as reference compound
      because of its known cytostatic properties and its activity as radical scavenger.
      Compared to quercetin the flavones induced little apoptosis (up to 40 microM),
      but despite their low toxicity, the Primula flavonoids possessed strong
      cytostatic properties even at low concentrations. The cell cycle distribution
      showed a characteristic time-dependent shift, giving evidence of a generally
      short-lived effect of the test compounds in the exposed cells. The antioxidative
      properties quantified according to two different methods correlated with the
      number of hydroxyl groups. Whereas quercetin strongly affected the mitochondrial
      membrane potential, none of the Primula flavones showed a comparable effect.

PMID- 14733503
TI  - Inhibitory effect of natural phenolic lipids upon NAD-dependent dehydrogenases
      and on triglyceride accumulation in 3T3-L1 cells in culture.
AB  - Alkylresorcinols are phenolic lipids present at levels of 0.03-0.15% in wheat and
      rye grains and almost 10 times higher in respective bran products. Despite
      numerous studies on the influence of dietary fibers on the regulation of energy
      metabolism, this issue still remains controversial. The objective of our current
      studies was to investigate whether 5-n-alk(en)ylresorcinols, natural phenolic
      components of high fiber human diets, may be considered as natural regulators of
      excessive fat accumulation. Our studies revealed that 5-n-alk(en)ylresorcinols
      isolated from wheat and rye bran inhibit glycerol-3-phosphate dehydrogenase, the
      key enzyme in triglyceride synthesis in adipocytes, specifically and effectively.
      Further in vitro studies showed that these compounds also prevent triglyceride
      accumulation in 3T3-L1 cells. The most effective compound in both systems was 5-n
      heneicosylresorcinol. The results indicate that the potential to prevent
      triglyceride accumulation increases with the hydrophobicity of the phenolic
      inhibitor.

PMID- 14733504
TI  - Investigation of the Origanum onites L. essential oil using the chorioallantoic
      membrane (CAM) assay.
AB  - The in vivo test on the chorioallantoic membrane of the fertilized hen's egg (CAM
      assay) is a current method to determine antiangiogenic, antiinflammatory activity
      and toxic effects of individual compounds or complex plant extracts. The method
      is used for testing natural compounds in small amounts for revealing various
      modes of action and the complex mechanisms related to angiogenesis and
      inflammation. Furthermore, possible side effects such as membrane irritation,
      toxic, and anticoagulant properties of the investigated material in question can
      be detected. For the evaluation, the essential oil obtained by hydrodistillation
      of the aerial parts of Origanum onites L., a common spice and medicinal plant,
      was tested for its effect in the chorioallantoic membrane (CAM) assay. The
      essential oil composition was revealed by means of gas chromatography-mass
      spectrometry (GC-MS). Eighty three components were identified, representing 99.1%
      of the total oil. Carvacrol, thymol, p-cymene, and gamma-terpinene were found as
      major components and were also individually tested in the CAM assay. Along with
      the monoterpenes carvacrol and thymol, their methyl ether derivatives were also
      examined for comparison of their physiological action. Neither the essential oil
      nor its components showed any pronounced antiinflammatory or antiangiogenic
      property in the CAM assay, at 10-250 microg/pellet. However, the irritant effect
      of the essential oil was linked to thymol in a dose-response fashion, up to 10
      microg/pellet, where it was still showing irritation.

PMID- 14733505
TI  - Major flavonoids in grape seeds and skins: antioxidant capacity of catechin,
      epicatechin, and gallic acid.
AB  - Grape seeds and skins are good sources of phytochemicals such as gallic acid,
      catechin, and epicatechin and are suitable raw materials for the production of
      antioxidative dietary supplements. The differences in levels of the major
      monomeric flavanols and phenolic acids in seeds and skins from grapes of Vitis
      vinifera varieties Merlot and Chardonnay and in seeds from grapes of Vitis
      rotundifolia variety Muscadine were determined, and the antioxidant activities of
      these components were assessed. The contribution of the major monomeric flavonols
      and phenolic acid to the total antioxidant capacity of grape seeds and skins was
      also determined. Gallic acid, monomeric catechin, and epicatechin concentrations
      were 99, 12, and 96 mg/100 g of dry matter (dm) in Muscadine seeds, 15, 358, and
      421 mg/100 g of dm in Chardonnay seeds, and 10, 127, and 115 mg/100 g of dm in
      Merlot seeds, respectively. Concentrations of these three compounds were lower in
      winery byproduct grape skins than in seeds. These three major phenolic
      constituents of grape seeds contributed <26% to the antioxidant capacity measured
      as ORAC on the basis of the corrected concentrations of gallic acid, catechin,
      and epicatechin in grape byproducts. Peroxyl radical scavenging activities of
      phenolics present in grape seeds or skins in decreasing order were resveratrol >
      catechin > epicatechin = gallocatechin > gallic acid = ellagic acid. The results
      indicated that dimeric, trimeric, oligomeric, or polymeric procyanidins account
      for most of the superior antioxidant capacity of grape seeds.

PMID- 14733506
TI  - Effect of fermentation and autoclaving on dietary fiber fractions and
      antinutritional factors of beans (Phaseolus vulgaris L.).
AB  - The effect of fermentation on antinutritional factors and also on total dietary
      fiber (TDF), insoluble (IDF) and soluble (SDF) dietary fiber fractions was
      studied in beans (Phaseolus vulgaris L.). The processes studied were two types of
      fermentation (lactic acid and natural), and a portion of the obtained flours were
      processed by autoclaving. The dietary fiber (DF) content and its components were
      determined using the enzymatic-gravimetric and enzymatic-chemical methods. The
      TDF content ranged from 24.5% dry matter (DM) in the raw to 25.2% DM in the
      processed beans. All the processing treatments significantly decreased the SDF
      content, and irrelevant changes were noticed in the IDF content of processed
      beans. Cellulose content of all samples was reduced by the processing treatments.
      Correspondingly, higher amounts of resistant starch was observed in the processed
      beans, except in the lactic acid fermented ones. However, the levels of pectic
      polysaccharides and Klason lignin were higher in the samples fermented by
      Lactobacillus plantarum. The action of microorganisms was determinant for the
      different degradation of the bean cell wall, disrupting the protein-carbohydrate
      integration, thus reducing the solubility of DF.

PMID- 14733507
TI  - Toward a high yield recovery of antioxidants and purified hydroxytyrosol from
      olive mill wastewaters.
AB  - We investigated to develop effective procedures to recover the potentially high
      added-value phenolic compounds contained in the discontinuous three-phase olive
      processing wastewaters (OMW). Particular emphasis was made to extract and purify
      hydroxytyrosol, one of the major compounds occurring in OMW. Batch optimization
      experiments showed that ethyl acetate is the most efficient solvent for the
      recovery of phenolic monomers from OMW. The latter was used with an optimal pH
      equal to 2. Furthermore, the percentage of each monomer, and particularly
      hydroxytyrosol, in the extract was maximum for a solvent ratio and a theoretical
      extraction stage number equal to 2 and 3, respectively. High yield (85.46%)
      recovery of hydroxytyrosol was achieved from OMW using a three-staged continuous
      counter-current liquid-liquid extraction unit. Hydroxytyrosol (1.225 g) were
      extracted per liter of OMW. One gram of hydroxytyrosol per liter of OMW was then
      purified by means of a chromatographic system which could be adapted to a large
      scale production process.

PMID- 14733508
TI  - Fatty acid and carotenoid composition of gac (Momordica cochinchinensis Spreng)
      fruit.
AB  - In this study, we analyzed fatty acid and carotenoid composition of fruit
      tissues, including seed (which are surrounded by a bright red, oily aril) of
      Momordica cochinchinensis Spreng, known as gac in Vietnam. Carotenoid content was
      analyzed by reversed-phase HPLC, using a C(30) column and a method separating cis
      and trans-isomers of the major carotenoids in this fruit. Mean values obtained
      in aril tissues were 1342 microg trans-, 204 microg cis-, and 2227 microg total
      lycopene; 597 microg trans-, 39 microg cis-, and 718 microg total beta-carotene;
      and 107 microg alpha-carotene/g FW. Mesocarp contained 11 microg trans-, 5 microg
      cis-beta-carotene/g FW, trace amounts of alpha-carotene, and no lycopene. Gac
      aril contained 22% fatty acids by weight, composed of 32% oleic, 29% palmitic,
      and 28% linoleic acids. Seeds contained primarily stearic acid (60.5%), smaller
      amounts of linoleic (20%), oleic (9%), and palmitic (5-6%) acids, and trace
      amounts of arachidic, cis-vaccenic, linolenic, and palmitoleic, eicosa-11-enoic
      acids, and eicosa-13-enoic (in one fruit only) acids.

PMID- 14733509
TI  - The degradation of the natural pyrethrins in crop storage.
AB  - Prolonged storage of harvested Tasmanian pyrethrum crop from Tanacetum
      cinerariaefolium has resulted in substantial losses of the pyrethrin esters due
      to the environmental conditions in the storage shed. The generation of heat, the
      presence of moisture and oxygen, and the microbial activity were identified as
      possible causes. A pyrethrum crop sample was divided up and stored in different
      conditions relating to these variables, and the pyrethrins content was monitored
      over time using a standard method. Temperature was determined to be a critical
      factor in the rate of the degradation of the natural pyrethrins. Moisture,
      oxygen, and microbial activity unexpectedly did not play a major role in the
      degradation. An initial rapid loss of the natural pyrethrins was observed before
      the pyrethrins content stabilized at a loss of around 65%. This suggests that the
      plant structure may provide chemical or physical protection to the pyrethrins. In
      all cases, the majority of the loss was attributed to the pyrethrin I and
      pyrethrin II esters.

PMID- 14733510
TI  - Rotenone and rotenoids in cube resins, formulations, and residues on olives.
AB  - Rotenone and rotenoids (deguelin, beta-rotenolone (12a beta-hydroxyrotenone),
      tephrosin (12a beta-hydroxydeguelin), 12a alpha-hydroxyrotenone, and
      dehydrorotenone) were determined in cube resins and formulations. Cube resins
      from Lonchocarpus contain large quantities of deguelin (ca. 21.2%) and smaller
      quantities of tephrosin (ca. 3.5%) and beta-rotenolone (ca. 3.0%). The
      composition of commercial formulations may present very different rotenoid
      contents depending on the extracts used to prepare them. Because these rotenoids
      also present insecticide activity, the efficacy of these formulations may be very
      different. The storage stability and photodegradation of some rotenone
      formulations were studied. Rotenone and rotenoids are very sensitive to solar
      radiation, which degrades them rapidly, with half-lives in the order of a few
      tens of minutes. Some formulations show greater disappearance rates than that of
      cube resin, indicating that not much attention has been paid to protecting the
      active ingredients from photodegradation in the formulation. A study on the
      residues on olives was also carried out to assess not only the rotenone content,
      but also that of the main rotenoids. At harvest, the residues of deguelin,
      tephrosin, and beta-rotenolone were 0.10, 0.06, and 0.10 mg/kg, respectively,
      very similar to rotenone (0.08 mg/kg), and though a few data indicate similar
      acute toxicity values for deguelin, only rotenone is taken into consideration in
      the legal determination of the residue.

PMID- 14733511
TI  - Use of a byproduct of magnesium oxide production to precipitate phosphorus and
      nitrogen as struvite from wastewater treatment liquors.
AB  - This paper describes a series of experiments designed to recover phosphorus and
      nitrogen from sewage in the form of struvite (MgNH(4)PO(4).6H(2)O), a potential
      fertilizer. Nitrogen and phosphate were recovered from a filtrate of digested
      sludge dewatered at the Arroyo del Soto Waste Water Treatment Plant (WWTP)
      (Madrid, Spain). A byproduct of the Spanish magnesite mining and MgO production
      industry was used as the magnesium source. The precipitating performance of this
      byproduct was compared to that of conventional chemical reagents such as pure
      MgO. The precipitates obtained were subjected to chemical, light microscopy, and
      X-ray diffraction analysis. The findings indicate the precipitate recovered using
      this byproduct contains several minerals with a predominance of struvite. Optimal
      purity ( approximately 80% struvite) was achieved using the sieved <0.04 mm grain
      size fraction of the byproduct at doses corresponding to a molar Mg:P ratio of
      1.6.

PMID- 14733512
TI  - Identification and sensory evaluation of volatile compounds in oxidized porcine
      liver.
AB  - Headspace solid phase microextraction (HS-SPME) was used to isolate the off
      flavor volatile compounds, which are formed during the oxidation of porcine liver
      induced by iron. Poly(dimethylsiloxane)/divinylbenzene fiber was used in the HS
      SPME. Changes in the volatile compounds of oxidized porcine liver and unsaturated
      fatty acids induced by iron were examined. Results showed that 1-octen-3-one
      (metallic), hexanol (weak metallic), 1-octen-3-ol (mushroomlike), (E)-2-nonenal
      (cardboardlike), and (E,E)-2,4-decadienal (fatty, oily) were the main
      contributors to the overall off-flavor of porcine liver. The results of the
      sensory evaluation revealed that oxidized arachidonic acid has a major impact on
      metallic and liverlike off-flavor and that when liverlike off-flavor is
      perceived, metallic is also included. Oxidized linolenic acid was the most
      important contributor to the objectionable fishy off-flavor. Oxidized porcine
      liver exhibited distinct metallic, liverlike, and weak fishy background notes.
      Liverlike flavor had a high correlation coefficient with odor characteristics
      such as metallic (0.839) and fishy (0.777). In this study, it was clearly
      observed that the stronger the metallic and fishy off-flavor the higher the
      perception of liverlike off-flavor.

PMID- 14733513
TI  - Identification and synthesis of 2-heptanethiol, a new flavor compound found in
      bell peppers.
AB  - 2-Heptanethiol was identified for the first time as a constituent of red and
      green bell pepper extracts. The chemical structure of this new aroma compound was
      proposed on the basis of mass spectra and retention indices and confirmed by
      chemical synthesis and nuclear magnetic resonance spectroscopy measurements. Its
      aroma properties were described as sulfury, onion-like, and vegetable-like,
      reminiscent of bell pepper at lower concentrations, with an orthonasal detection
      threshold of 10 microg/L of water. No differences in odor note and threshold
      value were observed for the enantiomeric forms, which were prepared from
      enantiopure 2-heptanol by tosylation, followed by thioacetylation and reduction,
      giving the target thiol enantiomers.

PMID- 14733514
TI  - Chemical and olfactometric characterization of volatile flavor compounds in a
      fish oil enriched milk emulsion.
AB  - Development of objectionable fishy off-flavors is an obstacle in the development
      of fish oil enriched foods. Only little is known about the sensory impact of
      specific volatile fish oil oxidation products in food emulsions. This study
      examined the volatiles profiles of fish oil enriched milk during cold storage (2
      degrees C) for 14 days by dynamic headspace sampling followed by gas
      chromatography-mass spectrometry analyses. Different volatiles (n = 60)
      comprising alkenals, alkadienals, alkatrienals, and vinyl ketones were identified
      in the fish oil enriched milk. The potent odorants identified by gas
      chromatography-olfactometry were 1-penten-3-one, (Z)-4-heptenal, 1-octen-3-one,
      (Z)-1,5-octadien-3-one, (E,E)-2,4-heptadienal, and (E,Z)-2,6-nonadienal, but
      despite their potency, none of the separated volatiles imparted a fishy or
      metallic odor. Two isomers, (E,Z,Z) and (E,E,Z) of 2,4,7-decatrienal were
      identified in fish oil enriched milk emulsions with peroxide values 0.8 and 3.4
      meq/kg, respectively. To our knowledge, this is the first report on appearance of
      these decatrienals in food emulsions having a relatively low peroxide value.

PMID- 14733515
TI  - Genotoxicity of melanoidin fractions derived from a standard glucose/glycine
      model.
AB  - Genotoxic compounds can act at various levels in the cell (causing gene,
      chromosome, or genome mutations), necessitating the use of a range of
      genotoxicity assays designed to detect these different types of mutations. The
      production of melanoidins during the processing and cooking of foods is
      associated with changes in their nutritional character, and the discovery of
      mutagenic substances in pyrolyzed protein and amino acids has raised concern
      about the safety of these foods. The aim of this work was to test melanoidin
      fractions in three different in vitro assays (Ames test, Vitotox test, and
      micronucleus test). These melanoidin fractions were produced from the
      condensation of glucose with glycine and their separation was conducted by
      dialysis. The crude reaction mixture (before dialysis) and both the LMW and HMW
      fractions obtained by dialysis showed no genotoxicity in these assays, despite
      being tested at concentrations much higher than those naturally found in food
      products. The LMW fraction, however, showed toxicity at these high
      concentrations. The volatile fraction produced in this reaction showed
      genotoxicity only in the Vitotox test, at high concentrations.

PMID- 14733516
TI  - Effect of the rootstock and interstock grafted in lemon tree (Citrus limon (L.)
      Burm.) on the flavonoid content of lemon juice.
AB  - The grafting of the rootstock with the lemon tree is an agronomical technique
      used to improve production and/or quality of the fruit. The interstock has been
      used with different fruit trees to modulate the tree size, fruit production and
      quality, and the aging of the tree. The lemon trees grafted with interstocks
      increase their longevity, lemon production and quality; interstocks are also used
      to decrease the thickness of the trunk at the grafting point. This enlarging of
      the trunk provokes a decrease of the sap flow. In our study, "Verna" lemon trees
      were grafted with interstock between the rootstock and the lemon tree to follow
      the flavonoid content of the lemon juice. The lemon juice was obtained from the
      lemons collected of the grafted lemon trees. Two types of rootstocks were used:
      Citrus aurantium L. and Citrus macrophylla L. Seven interstocks from five
      cultivars of orange tree, one cultivar of lime tree, and one cultivar of
      tangerine tree were used. "Verna" lemon trees were also grafted directly to the
      rootstock. The rootstock was more important agronomic factor than the interstock
      on the total flavonoid content of lemon juice. The interstock grafting had only a
      small influence on the flavonoid content of the lemon juice, and it modulated the
      individual flavonoid content. Citrus aurantium L. rootstock and "Berna" and
      "Washington Navel" interstocks were the most appropriate to graft in the lemon
      tree. This interstock grafting technique does not increase the flavonoid content
      of the lemon juice. Regarding the individual flavonoids, the 6,8-di-C-glucosyl
      diosmetin was the most affected flavonoid by the type of rootstock used. The
      interstock used is able to alter the individual quantitative flavonoid order of
      eriocitrin, diosmin, and hesperidin. In addition, the HPLC-ESI/MS(n) analyses
      provided the identification of two new flavonoids in the lemon juice: Quercetin 3
      O-rutinoside-7-O-glucoside and chrysoeriol 6,8-di-C-glucoside (stellarin-2). The
      occurrence of apigenin 6,8-di-C-glucoside (vicenin-2), eriodictyol 7-O
      rutinoside, 6,8-di-C-glucosyl diosmetin, hesperetin 7-O-rutinoside,
      homoeriodictyol 7-O-rutinoside and diosmetin 7-O-rutinoside was also confirmed in
      lemon juice by this technique.

PMID- 14733517
TI  - Growth temperature control of the linoleic acid content in safflower (Carthamus
      tinctorius) seed oil.
AB  - The temperature and oxygen regulation of the microsomal oleate desaturase (FAD2)
      from safflower (Carthamus tinctorius L.) seeds was investigated. Heat-resistance
      profiles obtained in vivo and in vitro showed that the FAD2 enzyme maintained its
      maximal activity until 30 degrees C. A temperature increase from 10 to 40 degrees
      C caused a decrease of the FAD2 activity. However, when the temperature was
      decreased from 40 to 10 degrees C, no increase in the activity level was
      detected. The removal of hulls from safflower seeds followed by incubation in air
      did not change the FAD2 activity level, whereas incubation under nitrogen caused
      a strong decrease. Air replacement brought about the recovery of the initials
      levels. Oxygen concentrations less than 3% produced the inactivation of the
      enzyme. These data indicate that the higher thermal stability and the lower
      dependence on oxygen availability of the safflower FAD2 enzyme, compared with
      that of sunflower, could be the main factors to explain why the linoleate content
      of safflower seeds is more independent of growth temperature than that of
      sunflower seeds.

PMID- 14733518
TI  - Rheological properties of acid gels prepared from heated pH-adjusted skim milk.
AB  - Reconstituted skim milk was adjusted to pH values between 6.5 and 7.1 and heated
      (90 degrees C) for up to 30 min. The skim milk samples were then readjusted to pH
      6.7. Acid gels prepared from heated milk had markedly higher G ' values, a
      reduced gelation time, and an increased gelation pH than those prepared from
      unheated milk. An increased pH at heating decreased the gelation time, increased
      the gelation pH, and increased the final G ' of acid set gels prepared from the
      heated milk samples. There were only small differences in the level of whey
      protein denaturation in the samples at different pH values, and these differences
      could not account for the differences in the G ' of the acid gels. The levels of
      denatured whey protein associated with the casein micelles decreased and the
      levels of soluble denatured whey proteins increased as the pH at heating was
      increased. The results indicated that the soluble denatured whey proteins had a
      greater effect on the final G ' of the acid gels than the denatured whey proteins
      associated with the casein micelles.

PMID- 14733519
TI  - Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and
      their oxygen radical absorbance capacity (ORAC).
AB  - Four new abscisic acid related compounds (1-4), together with (+)-abscisic acid
      (5), (+)-beta-D-glucopyranosyl abscisate (6), (6S,9R)-roseoside (7), and two
      lignan glucosides ((+)-pinoresinol mono-beta-D-glucopyranoside (8) and 3-(beta-D
      glucopyranosyloxymethyl)-2- (4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7
      methoxy-(2R,3S)-dihydrobenzofuran (9)) were isolated from the antioxidative
      ethanol extract of prunes (Prunus domestica L.). The structures of 1-4 were
      elucidated on the basis of NMR and MS spectrometric data to be rel-5-(3S,8S
      dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E
      pentadienoic acid (1), rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6
      oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid 3'-O-beta-d
      glucopyranoside (2), rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxa-6
      oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (3), and rel-5-(1R,5S
      dimethyl-3R,4R,8S-trihydroxy-7-oxabicyclo[3,2,1]- oct-8-yl)-3-methyl-2Z,4E
      pentadienoic acid (4). The antioxidant activities of these isolated compounds
      were evaluated on the basis of oxygen radical absorbance capacity (ORAC). The
      ORAC values of abscisic acid related compounds (1-7) were very low. Two lignans
      (8 and 9) were more effective antioxidants whose ORAC values were 1.09 and 2.33
      micromol of Trolox equiv/micromol, respectively.

PMID- 14733520
TI  - Influence of baking conditions and precursor supplementation on the amounts of
      the antioxidant pronyl-L-lysine in bakery products.
AB  - The influence of baking conditions and dough supplements on the amounts of the
      antioxidant and Phase II-Enzyme modulating, protein-bound 2,4-dihydroxy-2,5
      dimethyl-1-(5-acetamino-5-methoxycarbonyl-pentyl)-3-oxo-2H-pyrrol (pronyl-L
      lysine) in bakery products was investigated in quantitative studies. These
      studies revealed high amounts of the antioxidant in bread crust, only low amounts
      in the crumb, and the absence of this compound in untreated flour. The amounts of
      pronyl-L-lysine were found to be strongly influenced by the intensity of the
      thermal treatment. For example, increasing the baking time from 70 to 210 min or
      increasing the baking temperature from 220 to 260 degrees C led to a 5- or 3-fold
      increase in the concentrations of this antioxidant in the crust, respectively. In
      addition, modifications in the recipe showed to have a major impact on pronyl-L
      lysine formation. For example, substituting 5% of the flour with the lysine-rich
      protein casein or with 10% of glucose increased the amounts of the antioxidant by
      more than 200%. Quantitative analyses of commercial bread samples collected from
      German bakeries revealed the highest amount of 43 mg/kg for a full grain bread,
      followed by a rye/wheat bread, both of which have been sourdough fermented. A
      mixed-grain bread as well as pale wheat bread, both prepared without sourdough
      fermentation, contained significantly lower amounts of pronyl-L-lysine, and
      German pretzels, which are treated with a dilute sodium hydroxide solution prior
      to baking, contained only trace amounts of pronyl-L-lysine (e.g., less than 5
      mg/kg were detectable in pretzels). Systematic studies revealed that the decrease
      of the pH value induced by microbial acid formation during sourdough fermentation
      is the clue for producing high amounts of pronyl-L-lysine in baking products.
      These data clearly demonstrate for the first time that the amounts of the
      antioxidant and chemopreventive compound pronyl-L-lysine in bakery products is
      strongly dependent on the manufacturing conditions as well as the recipe.

PMID- 14733521
TI  - Interactions between beta-lactoglobulin and pectins during in vitro gastric
      hydrolysis.
AB  - This paper deals with the influence of different levels of three pectins, low
      methylated pectin (LMP), high-methylated pectin (HMP), and low-methylated and
      amidated pectin (LMA), on the in vitro gastric hydrolysis of beta-lactoglobulin
      (beta-lg). Proteolysis by pepsin consisted of a 2-h progressive reduction of pH.
      A turbidity measurement of beta-lg-pectin mixtures was carried out during the
      proteolysis. The influence of pectins on pepsin enzymatic activity was also
      evaluated. beta-Lg was resistant to peptic digestion. The presence of each of the
      three pectins at a concentration of 50 wt % increased the N release at all pH
      values considered, despite a significant inhibition of the pepsin enzymatic
      activity with the pectins. The turbidity of beta-lg solutions during proteolysis
      was reduced by the addition of pectins, because of the formation of electrostatic
      complexes between this protein and pectins. The increase of N release could be a
      false positive result due to the difficulty of precipitating protein by
      trichloroacetic acid because of the formation of electrostatic complexes
      demonstrated by the decrease of turbidity.

PMID- 14733522
TI  - Fruit maturity and juice extraction influences ellagic acid derivatives and other
      antioxidant polyphenolics in muscadine grapes.
AB  - Polyphenolic compounds including ellagic acid, ellagic acid derivatives, and
      anthocyanins were characterized and quantified by novel chromatographic
      conditions in eight muscadine grape (Vitis rotundifolia) cultivars and evaluated
      for antioxidant capacity as influenced by two ripening stages and their location
      within the fruit (skin, pulp, and juice). All polyphenolics generally increased
      as fruit ripened and the highest concentrations were located in the skins. Free
      ellagic acid, ellagic acid glycosides, and total ellagic acid ranged from 8 to
      162, 7 to 115, and 587 to 1900 mg/kg, respectively, in the skin of ripe grapes.
      Hot-pressed juices contained considerably lower polyphenolic concentrations than
      were present in whole grapes. Five anthocyanidins were present in each cultivar
      in variable concentrations (delphinidin > petunidin > malvidin + peonidin >
      cyanidin). Antioxidant capacity was appreciably influenced by cultivar, maturity,
      and location in the fruit with good correlations to soluble phenolics found in
      both methanolic and ethyl acetate extracts (r = 0.83 and 0.92, respectively).

PMID- 14733523
TI  - Model studies on the photosensitized isomerization of bixin.
AB  - The photosensitized isomerization reaction of the natural cis carotenoid bixin
      (methyl hydrogen 9'-cis-6, 6'-diapocarotene-6, 6'-dioate) with rose bengal or
      methylene blue as the sensitizer in acetonitrile/methanol (1:1) solution was
      studied using UV-vis spectroscopy, high-performance liquid chromatography (HPLC),
      and time-resolved spectroscopic techniques, such as laser-flash photolysis and
      singlet oxygen phosphorescence detection. In both N(2)- and air-saturated
      solutions, the main product formed was all-trans-bixin. The observed
      isomerization rate constants, k(obs), decreased in the presence of air or with
      increase in the bixin concentration, suggesting the participation of the excited
      triplet state of bixin, (3)Bix, as precursor of the cis--> trans process. On the
      other hand, bixin solutions in the absence of sensitizer and/or light did not
      degrade, indicating that the ground state of bixin is stable to thermal
      isomerization at room temperature. Time-resolved spectroscopic experiments
      confirmed the formation of the excited triplet state of bixin and its
      deactivation by ground state bixin and molecular oxygen quenching processes. The
      primary isomerization products only degraded in the presence of air and under
      prolonged illumination conditions, probably due to the formation of oxidation
      products by reaction with singlet molecular oxygen. An energy-transfer mechanism
      was used to explain the observed results for the bixin transformations, and the
      consequences for food color are discussed.

PMID- 14733524
TI  - Far-infrared radiation increases the antioxidant properties of rice hull extract
      in cooked turkey meat.
AB  - To determine the antioxidant effects of rice hull extract exposed to far-infrared
      radiation, the added extracts were compared with sesamol in cooked turkey breast.
      Rice hull extract showed antioxidant properties in cooked turkey breast by
      reducing lipid oxidation and volatile aldehydes. Far-infrared radiation increased
      significantly the antioxidant activities of rice hull extracts. Rice hull extract
      irradiated by far-infrared (FRH) had lower TBARS values and fewer volatile
      aldehydes (hexanal, pentanal, and propanal) than a non-irradiated extract (IRH)
      during the 3 days of aerobic storage. Addition of FRH at 0.2% (w/w) in turkey
      meat could reduce the amounts of volatile hexanal to 18-47% of the control during
      the storage. However, the antioxidant activities of rice hull extracts did not
      last as long as those of pure sesamol due to the relatively low concentration of
      phenolics, and the extracts had some peculiar odor. Addition of rice hull
      extracts also increased both a and b values of the samples due to its brown
      intensity.

PMID- 14733525
TI  - Effect of fermentation on Sweetpotato (Ipomoea batatas) toxicity in mice.
AB  - Unfortunate bovine fatalities occurring after ingestion of mold-damaged
      sweetpotatoes preclude the use of the culled tubers in livestock feed. In cattle,
      mold-damaged sweetpotatoes induce an acute respiratory distress syndrome
      resulting in asphyxiation. Because of this potential toxicity and the general
      abundance of culled sweetpotatoes, the detoxification efficacy of ensiling was
      explored since it is an easy and economically viable technique often applied to
      preserve livestock feed. Sweetpotato slices with or without mold damage were
      stored either frozen (to represent unfermented samples) or fermented for 6 weeks
      at room temperature. Following fermentation, organic extracts were generated for
      administration to mice. Thirty hours following administration of the extracts,
      mice were evaluated for gross and microscopic lesions affecting the lungs, liver,
      and kidneys. Fermentation of 6 weeks duration was observed to inadequately
      eliminate the lung, liver, and kidney toxicity caused by mold-damaged
      sweetpotatoes. In fact, fermentation exacerbated the hepatotoxicity of mold
      damaged sweetpotatoes. This is also the first demonstration that sweetpotato
      regions lacking visible mold damage can induce lung and kidney injury, which,
      however, is preventable by fermentation.

PMID- 14733526
TI  - Conjugate of palladium(II) complex and beta-cyclodextrin acts as a biomimetic
      peptidase.
AB  - We combined the newly discovered ability of [Pd(H2O)4]2+ to residue-selectively
      hydrolyze X-Pro bonds in peptides at 6 </= pH </= 9 with the known ability of
      beta-cyclodextrin to recognize aromatic side chains and synthesized a conjugate
      reagent that acts as a sequence-specific peptidase. This new reagent cleaved the
      Ser6-Pro7 amide bond in bradykinin at pH 7. ROESY 1H NMR spectra gave evidence
      for inclusion of the side chain of Phe8 in the beta-cyclodextrin cavity, the
      interaction that makes the cleavage sequence specific.

PMID- 14733527
TI  - Improved treatment of the protein backbone in empirical force fields.
AB  - Empirical force field-based calculations of proteins, including protein-folding
      studies, have improved our understanding of the relationship of their structure
      to their biological function. However, limitations in the accuracy of empirical
      force fields in the treatment of the peptide backbone exist. Presented is a grid
      correction approach to improve the treatment of the peptide backbone phi/psi
      conformational energies. Inclusion of this correction with the CHARMM22 all-atom
      protein force field is shown to lead to significant improvement in the treatment
      of the conformational energies of both the peptide model compound, the alanine
      dipeptide, and of proteins in their crystal environment. The developed approach
      is suggested to lead to significant improvements in the accuracy of empirical
      force fields to treat peptides and proteins.

PMID- 14733528
TI  - The reaction of N-methyl-1,2,4-triazoline-3,5-dione with
      tetracyclopropylethylene. Formation of an unusual meso-ionic product and its
      rearrangement to the diazetidine.
AB  - The reaction of N-methyl-1,2,4-triazoline-3,5-dione and tetracyclopropylethylene
      results in the quantitative formation of a meso-ionic compound. The formation of
      this unusual compound is likely the result of the unique conformational and
      steric properties of the cyclopropyl groups which inhibit the expected reaction
      pathways. The meso-ionic compound undergoes an unprecedented rearrangement to the
      diazetidine upon warming to 55 degrees C.

PMID- 14733529
TI  - Conclusive evidence for a retention-retention pathway for the molybdenum
      catalyzed asymmetric alkylation.
AB  - Enantiomerically enriched, deuterated branched carbonates (Z)-(S)-PhCH(O2COMe)
      CH=CHD (1a), (Z)-(R)-PhCH(O2COMe)CH=CHD (2a), and linear carbonate (E)-(S)
      PhCH=CHCHD(O2COMe) (12) were employed as probes in the Mo-catalyzed asymmetric
      allylic alkylation with sodium dimethyl malonate, catalyzed by ligand complex 10
      derived from the mixed benzamide/picolinamide of (S,S)-trans-diaminocyclohexane
      and (norbornadiene)Mo(CO)4. X-ray crystallography, along with solution NMR
      structural analysis of the pi-allyl intermediate and competition experiments,
      conclusively established the reaction proceeded via a retention-retention
      pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic
      alkylations, which proceed via an inversion-inversion pathway.

PMID- 14733530
TI  - Thermal stability of the secondary structure of poly(alpha,L-glutamate) in self
      assembled complexes as studied by molecular dynamics in chloroform solution.
AB  - The thermal stability of the self-assembled complexes formed by
      alkyltrimethylammonium surfactants and poly(alpha,l-glutamate) is investigated in
      dilute chloroform solution by molecular dynamics simulations. By applying
      temperatures ranging from 300 to 500 K, we observed an extraordinary stability of
      the alpha-helix adopted by the polypeptide during a total of 48 ns. The multiple
      electrostatic interactions formed between the surfactant chains and the polyanion
      play a crucial role in this stability since they are responsible for the
      inaccessibility of the solvent molecules to the helix even at high temperatures.

PMID- 14733531
TI  - Catalytic asymmetric total syntheses of quinine and quinidine.
AB  - The catalytic, asymmetric syntheses of quinine and quinidine were achieved in 16
      steps. The recently developed salen(Al)-catalyzed enantioselective Michael
      addition of methyl cyanoacetate served to set the crucial C4 stereocenter in 92%
      ee, and a late-stage asymmetric dihydroxylation was used to differentiate the
      common intermediate and access the two desired diastereomeric products with high
      selectivity.

PMID- 14733532
TI  - Single-crystal CdSe nanosaws.
AB  - We report the first successful synthesis and characterization of single-crystal
      wurtzite CdSe nanoribbons through a simple thermal evaporation process.
      Asymmetric growth of the nanoribbons occurs, yielding a sawlike shape with sharp
      teeth on one side. This asymmetric growth is suggested to be induced by the
      polarization of the c-plane in the wurtzite crystal structure.

PMID- 14733533
TI  - Isolation of a stable covalent selenium azide RSeN3.
AB  - The first covalent selenium azide 2-Me2NCH2C6H4SeN3 has been synthesized and
      fully characterized including crystal structure determination. As shown by the
      experimental results, the relative stability of RSeN3 highly depends on the
      nature of the coordinating ability of the substituent R, resulting in a
      heterocyclic zwitterionic structure.

PMID- 14733534
TI  - Emission ratiometric imaging of intracellular zinc: design of a benzoxazole
      fluorescent sensor and its application in two-photon microscopy.
AB  - Zinc and calcium are ubiquitous intracellular metals, and while a variety of
      quantitative probes have been developed for measuring intracellular changes in
      calcium concentration, the same is not true of zinc. We describe here the design,
      synthesis, and properties of the benzoxazole-based, ratiometric zinc probe, Zinbo
      5. This bright fluorescent reporter has a quantum yield of 0.1 in the zinc-form,
      exhibits a Kd for Zn2+ in the nanomolar range, and shows significant changes in
      both excitation and emission maxima upon zinc binding. The utility of this cell
      permeable probe is demonstrated in fluorescence microscopy emission ratio imaging
      experiments on mammalian cells. We further show that Zinbo-5 is well suited for
      two-photon excitation microscopy ratio imaging and can readily reveal changes in
      intracellular zinc concentration within optical planes of single cells. To the
      best of our knowledge, this is the first example of two-photon excitation
      microscopy applied to ratio imaging of zinc. These methods can be applied to real
      time emission or excitation ratio imaging studies of zinc physiology in living
      cells.

PMID- 14733535
TI  - An amphiphilic approach to nanocrystal quantum dot-titania nanocomposites.
AB  - The addition of octylamine-modified poly(acrylic acid) to nanocrystal quantum
      dots (NQDs) results in robust, alcohol-soluble nanoparticles that can be readily
      incorporated into titania matrices without large changes in photoluminescence
      quantum yields. This approach relies on the amphiphilic nature of the polymer to
      create an NQD-polymer complex in which the alkyl chains interact with the
      hydrophobic part of the NQD, leaving the polar carboxylic acid groups on the
      periphery. This procedure is applicable to hydrophobically capped NQDs of a
      variety of shapes and compositions, making it a truly generalized route to
      nanocrystal-titania nanocomposites.

PMID- 14733536
TI  - Chiroptical transcription of helical information through supramolecular
      harmonization with dynamic helices.
AB  - With biologically important "peptide bundling" as the motif, new chromophoric
      cyclic host 1 was designed, which consists of two zinc porphyrin units that are
      connected by dynamic peptide helices of nonameric aminoisobutyric acid (Aib)
      units. Upon inclusion of pyridine-anchored helical peptides between the zinc
      porphyrin units, 1 displayed an intense exciton-coupled circular dichroism (CD)
      band at 410-450 nm, whose sign reflected the helical sense of the guest peptides.
      Studies with conformationally defined dehydrophenylalanine-containing analogues
      indicated that the dynamic helical chains in the host are stereochemically
      harmonized with right- or left-handed helices of the guest peptides in a confined
      nano space, leading to either clockwise- or anticlockwise-twisted geometry
      (chiroptical output) of the connecting zinc porphyrin chromophores.

PMID- 14733537
TI  - Exo selective enantioselective nitrone cycloadditions.
AB  - We have developed a novel method for accessing exo adducts with high
      enantioselectivity in nitrone cycloadditions to enoates. Pyrazolidinones proved
      to be effective achiral templates in the cycloadditions, providing exo adducts
      typically in >15:1 selectivity and 90-98% ee. The use of Lewis acids that form
      square planar complexes, such as copper triflate, was important for obtaining
      high exo selectivity.

PMID- 14733538
TI  - Lysine peroxycarbamates: free radical-promoted peptide cleavage.
AB  - Strategies are reported that combine in one step a predictable chemical-based
      protein digestion with mass spectrometry. Lysine residue amino groups in peptides
      and proteins are modified by reaction with a peroxycarbonate derived from p
      nitrophenol, and tert-butyl hydroperoxide. The peroxycarbonate reacts with lysine
      residues in peptides and proteins, and the resulting lysine peroxycarbamates
      undergo homolytic fragmentation under conditions of low-energy collision-induced
      dissociation (CID). Observed fragmentation of the peptides involves apparent free
      radical processes including Hofmann-Loffler-type rearrangements that lead to
      peptide chain fragmentation. Strategies for directed cleavage of peptides by free
      radical promoted processes are feasible, and such strategies may well simplify
      schemes for protein analysis.

PMID- 14733540
TI  - The site of Cr+ attachment to gas-phase aniline from infrared spectroscopy.
AB  - Infrared spectroscopy of gas-phase Cr+ complexes of aniline was studied using the
      FELIX free electron laser interfaced to a Fourier transform ion cyclotron
      resonance spectrometer. For both the monomer complex Cr+(aniline) and the dimer
      complex Cr+(aniline)2 the spectra showed features indicating binding of the metal
      ion to the aromatic pi cloud, as opposed to the nitrogen atom. Agreement with DFT
      calculated infrared absorption spectra for the ring-bound complexes was good
      using the MPW1PW91 functional, but the B3LYP functional predicted the wrong
      binding site. The spectroscopic results resolve the ambiguity in computational
      prediction of the preferred binding site and support the use of the MPW1PW91
      functional for these systems.

PMID- 14733539
TI  - Sequence-specific detection of MicroRNAs by signal-amplifying ribozymes.
AB  - The rational and straightforward design of hairpin ribozymes that can be sequence
      specifically induced by external oligonucleotides is described. Due to intrinsic
      signal amplification, their sensitivity is at least an order of magnitude
      increased compared to standard molecular beacons. We applied this system to the
      detection of microRNAs, a recently discovered class of small endogenous RNA
      molecules that are involved in gene regulation. We show that the cognate microRNA
      can reliably and sensitively be detected at low concentrations in a mix of other
      microRNA sequences. These probes may be useful in applications that require
      direct detection of minute amounts of small DNAs or RNAs.

PMID- 14733541
TI  - A recoverable enzymatic microgel based on biomolecular recognition.
AB  - The enzyme beta-galactosidase has been immobilized through incorporation into a
      selectively soluble microgel, prepared from DNA, biotinylated peptide nucleic
      acid (PNA), and the protein avidin. The enzyme was conjugated to avidin, allowing
      it to be integrated directly into the microgel network. Efficient hydrolysis of a
      small-molecule substrate occurred at 37 degrees , but cooling and centrifuging
      led to precipitation of the microgels and product separation. The microgels were
      then reconstituted by adding fresh buffer and shaking. The enzymatic activity was
      completely recovered through repeated cycles. This method should be generalizable
      to a wide variety of other enzymes and substrates.

PMID- 14733542
TI  - A general strategy to convert the MerR family proteins into highly sensitive and
      selective fluorescent biosensors for metal ions.
AB  - The MerR family metal-regulatory proteins are converted into fluorescent
      biosensors that can detect different metal ions with high sensitivity and
      selectivity.

PMID- 14733543
TI  - A robust nanocontainer based on a pure organic free radical.
AB  - A new pure organic paramagnetic porous molecular material, which combines
      hydrophilic windows with large hydrophobic nanocontainers, is shown to be stable
      even in absence of solvent guest molecules.

PMID- 14733544
TI  - An unprecedented memory of macromolecular helicity induced in an achiral
      polyisocyanide in water.
AB  - We have found an unprecedented memory of macromolecular helicity induced in an
      achiral sodium salt of poly(4-carboxyphenyl isocyanide) (poly-1-Na). Poly-1-Na
      folds into a one-handed helix through configurational isomerization around the
      C=N backbones by interactions with optically active amines in water. The helix
      remains when the optically active amines are completely removed, and further
      modifications of the side group to carboxy and esters can be possible without
      loss of the macromolecular helicity memory.

PMID- 14733545
TI  - Helical supramolecules and fibers utilizing leucine zipper-displaying dendrimers.
AB  - We describe a new family of discrete supramolecules comprising leucine-zipper
      peptides noncovalently assembled upon cognate leucine zippers fused to a
      dendrimer core. Circular dichroism and sedimentation equilibrium experiments
      clearly demonstrate that each leucine-zipper dendrimer (D-EZ4 or D-KZ4) can
      noncovalently display four leucine zippers on their surface that can be utilized
      for the multivalent display of protein cargo. Furthermore, we show that matched
      leucine-zipper dendrimers (D-EZ4/D-KZ4) can self-organize into fibers at neutral
      pH, providing a new scaffold for nanotechnology.

PMID- 14733546
TI  - Chemical synthesis of normal and transformed PSA glycopeptides.
AB  - Chemical syntheses are reported for prostate specific antigen (PSA) N-linked
      glycopeptide fragments consisting of an uneicosapeptide (residues 27-47 of PSA)
      with di-, tri-, and tetrabranched N-acetyllactosamine-type glycans. The syntheses
      involve simultaneous, multiple glycosylations of the corresponding
      pentasaccharide acceptors prepared from a common trisaccharide precursor.
      Globally deprotected glycans are aminated and then aspartylated with a
      hexapeptide, which is then extended using native chemical ligation (NCL). The
      glycopeptides will be used for the generation of antibodies that may form the
      basis for a new prostate cancer diagnostic assay.

PMID- 14733547
TI  - Control of protein structure and function through surface recognition by tailored
      nanoparticle scaffolds.
AB  - Thioalkyl and thioalkylated oligo(ethylene glycol) (OEG) ligands with chain-end
      functionality were used to fabricate water-soluble CdSe nanoparticle scaffolds.
      Surface recognition of chymotrypsin (ChT) was achieved using these functionalized
      nanoparticle scaffolds, with three levels of interaction demonstrated: no
      interaction (OEG terminated with hydroxyl group), inhibition with denaturation
      (carboxylate-terminated thioalkyl ligands), and inhibition with retention of
      structure (carboxylate-terminated OEG). The latter process was reversible upon an
      increase in ionic strength, with essentially complete restoration of enzymatic
      activity.

PMID- 14733548
TI  - Nature of the chemical bond formed with the structural metal ion at the A9/G10.1
      motif derived from hammerhead ribozymes.
AB  - We have studied the interaction between metal ions and the metal ion-binding
      motif in hammerhead ribozymes, as well as the functions of the metal ion at the
      motif, with heteronuclear NMR spectroscopy. In this study, we employed model RNA
      systems which mimic the metal ion-binding motif and the altered motif. In
      Co(NH3)6(III) titrations, we observed large 1H and 31P chemical shift
      perturbations for the motif and found that outer-sphere complexation of
      Co(NH3)6(III) is possible for this motif. From the reinvestigation of our
      previous 15N chemical shift data for Cd(II) binding, in comparison with those of
      organometallic compounds, we conclude that Cd(II) can form an inner-sphere
      complex with the nucleobase in the motif. Therefore, the A9/G10.1 site was found
      to accept both inner-sphere and outer-sphere complexations. The Mg(II) titration
      for a slightly different motif from the A9/G10.1 site (G10.1-C11.1 to A10.1
      U11.1) revealed that its affinity to Mg(II) was drastically reduced, although the
      ribozyme with this altered motif is known to retain enzymatic activities. This
      observation suggests that the metal ion at these motifs is not a catalytic center
      of hammerhead ribozymes.

PMID- 14733549
TI  - Characterization of micros-ms dynamics of proteins using a combined analysis of
      15N NMR relaxation and chemical shift: conformational exchange in plastocyanin
      induced by histidine protonations.
AB  - An approach is presented that allows a detailed, quantitative characterization of
      conformational exchange processes in proteins on the micros-ms time scale. The
      approach relies on a combined analysis of NMR relaxation rates and chemical shift
      changes and requires that the chemical shift of the exchanging species can be
      determined independently of the relaxation rates. The applicability of the
      approach is demonstrated by a detailed analysis of the conformational exchange
      processes previously observed in the reduced form of the blue copper protein,
      plastocyanin from the cyanobacteria Anabaena variabilis (A.v. PCu) (Ma, L.; Hass,
      M. A. S.; Vierick, N.; Kristensen, S. M.; Ulstrup, J.; Led, J. J. Biochemistry
      2003, 42, 320-330). The R1 and R2 relaxation rates of the backbone 15N nuclei
      were measured at a series of pH and temperatures on an 15N labeled sample of A.v.
      PCu, and the 15N chemical shifts were obtained from a series of HSQC spectra
      recorded in the pH range from 4 to 8. From the R1 and R2 relaxation rates, the
      contribution, Rex, to the transverse relaxation caused by the exchanges between
      the different allo-states of the protein were determined. Specifically, it is
      demonstrated that accurate Rex terms can be obtained from the R1 and R2 rates
      alone in the case of relatively rigid proteins with a small rotational
      anisotropy. The Rex terms belonging to the same exchange process were identified
      on the basis of their pH dependences. Subsequently the identifications were
      confirmed quantitatively by the correlation between the Rex terms and the
      corresponding chemical shift differences of the exchanging species. By this
      approach, the Rex terms of 15N nuclei belonging to contiguous regions in the
      protein could be assigned to the same exchange process. Furthermore, the analysis
      of the exchange terms shows that the observed micros-ms dynamics in A.v. PCu are
      caused primarily by the protonation/deprotonation of two histidine residues,
      His92 and His61, His92 being ligated to the Cu(I) ion. Also the exchange rate of
      the protonation/deprotonation process of His92 and its pH and temperature
      dependences were determined, revealing a reaction pathway that is more complex
      than a simple specific-acid/base catalysis. Finally, the approach allows a
      differentiation between two-site and multiple-site exchange processes, thus
      revealing that the protonation/deprotonation of His61 is at least a three-site
      exchange process. Overall, the approach makes it feasible to obtain exchange
      rates that are sufficiently accurate and versatile for studies of the kinetics
      and the mechanisms of local protein dynamics on the sub-millisecond time scale.

PMID- 14733550
TI  - Peralkylated coronenes via regiospecific hydrogenation of hexa-peri
      hexabenzocoronenes.
AB  - A remarkable, regiospecific hydrogenation zips around the approximately 4 nm
      perimeter of hexa-peri-hexabenzocoronenes (HBC) adding 18 hydrogen atoms, leading
      to the first peralkylated coronenes, in quantitative yields in some cases.
      Increasing steric bulk of side chains was found to hinder the reaction, while
      unsubstituted HBC could be converted to a modest extent despite its vanishing
      solubility. The structures of the novel coronenes are unequivocally confirmed by
      MALDI-TOF, 1H, 13C, and heteronuclear correlation NMR, and UV-vis absorption
      spectroscopy. The puckered-ring periphery of these discotics does not prohibit
      self-assembly to columnar structures in a fashion similar to that of the planar
      precursors, as determined from wide-angle X-ray diffraction, but decreases the
      isotropization temperature by approximately 300 degrees C relative to the latter.
      Branching in the alkyl chains frustrates nucleation from the melt, resulting in
      clear polymorphism depending on the thermal treatment. Nonetheless, preliminary
      measurements indicate high charge-carrier mobilities and lifetimes within the
      bulk material, on the same order as those previously found for HBCs.

PMID- 14733551
TI  - Photochemistry and mobility of stilbenoid dendrimers in their neat phases.
AB  - Selectively deuterated, dodecyloxy substituted stilbenoid dendrimers of the first
      and second generation were synthesized by a convergent synthesis, using the
      Wittig-Horner reaction. The photochemistry and the fluorescence in the different
      crystalline and liquid crystalline phases were investigated. Molecules deuterated
      at the alpha-position of the alkoxy chains were used to study the photoreactions
      in the neat phases by 1H NMR. Reactions of the double bonds are exclusively
      observed in the liquid crystal phases. No photoreactions occur in the crystalline
      state. The mobility of the dendrimers was studied by means of 2H solid-state NMR
      spectroscopy. The onset of the photochemistry for dendrimer 1 [all-(E)-1,3,5
      tris[2-(3,4,5-tridodecyloxyphenyl)ethenyl]benzene] corresponds to the increasing
      mobility at the Cr/LC transition. The first generation dendrimers still show
      large angle motion, whereas dendrimers of the second generation 2 [all-(E)-1,3,5
      tris(2-[3,5-bis[2-(3,4,5-tridodecyloxyphenyl)ethenyl]phenyl]ethenyl)benzene] are
      restricted to librational motions. Photochemical conversion and fluorescence
      quenching for first and second generation dendrimers 1 and 2 increase with
      increasing molecular motion and reach a maximum in the isotropic phase.

PMID- 14733552
TI  - Solid-state induced control of kinetically unstable stereoisomers.
AB  - Arene complexes of the form TpM(pi-acid)(L)(eta2-arene) (Tp =
      hydridotris(pyrazolyl)borate, M = Re, Mo, or W, pi-acid = CO or NO, L = 1
      alkylimidazole, pyridine, PMe3, arene is prochiral) exist as a dynamic
      equilibrium of coordination diastereomers in solution. In both crystalline and
      amorphous solid states, however, only one diastereomer is present. Reactions on
      the bound arenes in these complexes have been performed stereoselectively, by
      exploiting the homomorphic nature of the solid phase.

PMID- 14733553
TI  - Unexpectedly fast cis/trans isomerization of Xaa-Pro peptide bonds in disulfide
      constrained cyclic peptides.
AB  - Acyclic dithiol and cyclic disulfide forms of the peptides Ac-Cys-Pro-Xaa-Cys-NH2
      (Xaa = Phe, His, Tyr, Gly, and Thr) and Ac-Cys-Gly-Pro-Cys-NH2 and the peptide Ac
      Ala-Gly-Pro-Ala-NH2 were synthesized and characterized by mass spectrometry and
      NMR spectroscopy. Rate constants kct and ktc for cis-to-trans and trans-to-cis
      isomerization, respectively, across the Cys-Pro or Gly-Pro peptide bonds were
      determined by magnetization transfer NMR techniques over a range of temperatures,
      and activation parameters were derived from the temperature dependence of the
      rate constants. It was found that constraints imposed by the disulfide bond
      confer an unexpected rate enhancement for cis/trans isomerization, ranging from a
      factor of 2 to 13. It is proposed that the rate enhancements are a result of an
      intramolecular catalysis mechanism in which the NH proton of the Pro-Xaa peptide
      bond hydrogen bonds to the proline nitrogen in the transition state. The peptides
      Ac-Cys-Pro-Xaa-Cys-NH2 and Ac-Cys-Gly-Pro-Cys-NH2 are model compounds for proline
      containing active sites of the thioredoxin superfamily of oxidoreductase enzymes;
      the results suggest that the backbones of the active sites of the oxidized form
      of these enzymes may have unusual conformational flexibility.

PMID- 14733554
TI  - Formation of Zn(1-x)MnxS nanowires within mesoporous silica of different pore
      sizes.
AB  - Arrays of highly ordered Zn(1-x)MnxS quantum wires with x ranging from 0.01 to
      0.3 and with lateral dimensions of 3, 6, and 9 nm were synthesized within
      mesoporous SiO2 host structures of the MCM-41 and SBA-15 type. The hexagonal
      symmetry of these arrays (space group p6m) and the high degree of order was
      confirmed by X-ray diffraction and transmission electron microscopy (TEM)
      studies. Physisorption measurements show the progressive filling of the pores of
      the SiO2 host structures, while TEM and Raman studies reveal the wire-like
      character of the incorporated Zn(1-x)MnxS nanostructures. X-ray absorption near
      edge structure, extended X-ray absorption fine structure, photoluminescence
      excitation (PLE), and electron paramagnetic resonance studies confirm the good
      crystalline quality of the incorporated Zn(1-x)MnxS guest species and, in
      particular, that the Mn2+ ions are randomly distributed and are situated on
      tetrahedrally coordinated cation sites of the Zn(1-x)MnxS wires for all x up to
      0.3. The amount of Mn2+ ions loosely bound to the surface of the Zn(1-x)MnxS
      nanowires is less than 4% of the total Mn content even for the 3 nm
      nanostructures up to the highest Mn content of x = 0.3. The effects of the
      reduction of the lateral dimensions on electronic properties of the diluted
      magnetic semiconductor were studied by PLE spectroscopy. Due to the quantum
      confinement of the excitons in the wires an increase of the direct band gap with
      decreasing particle size is observed.

PMID- 14733556
TI  - First-principle predictions of absolute pKa's of organic acids in dimethyl
      sulfoxide solution.
AB  - MP2/6-311++G(d,p) and B3LYP/6-311++G(2df,p) methods were found to be able to
      predict the gas-phase acidities of various organic acids with a precision of 2.2
      and 2.3 kcal/mol. A PCM cluster-continuum solvation method was developed that
      could predict the solvation free energies of various neutral, cationic, and
      anionic organic species in DMSO with a precision of about 2.0 kcal/mol. Using
      these carefully tested methods, we successfully predicted the pKa's of 105
      organic acids in DMSO with a precision of 1.7-1.8 pKa units. We also predicted
      the pKa's of a variety of organosilanes in DMSO for the first time using the
      newly developed methods. This study was one of the first that employed first
      principle methods for calculating pKa's of unrelated compounds in organic
      solutions.

PMID- 14733555
TI  - Kinetics of end-to-end collision in short single-stranded nucleic acids.
AB  - A novel fluorescence-based method, which entails contact quenching of the long
      lived fluorescent state of 2,3-diazabicyclo[2.2.2]-oct-2-ene (DBO), was employed
      to measure the kinetics of end-to-end collision in short single-stranded
      oligodeoxyribonucleotides of the type 5'-DBO-(X)n-dG with X = dA, dC, dT, or dU
      and n = 2 or 4. The fluorophore was covalently attached to the 5' end and dG was
      introduced as an efficient intrinsic quencher at the 3' terminus. The end-to-end
      collision rates, which can be directly related to the efficiency of
      intramolecular fluorescence quenching, ranged from 0.1 to 9.0 x 10(6) s(-1). They
      were strongly dependent on the strand length, the base sequence, as well as the
      temperature. Oligonucleotides containing dA in the backbone displayed much slower
      collision rates and significantly higher positive activation energies than
      strands composed of pyrimidine bases, suggesting a higher intrinsic rigidity of
      oligoadenylate. Comparison of the measured collision rates in short single
      stranded oligodeoxyribonucleotides with the previously reported kinetics of
      hairpin formation indicates that the intramolecular collision is significantly
      faster than the nucleation step of hairpin closing. This is consistent with the
      configurational diffusion model suggested by Ansari et al. (Ansari, A.;
      Kuznetsov, S. V.; Shen, Y. Proc.Natl. Acad. Sci. USA 2001, 98, 7771-7776), in
      which the formation of misfolded loops is thought to slow hairpin formation.

PMID- 14733557
TI  - New 1H-pyrazole-containing polyamine receptors able to complex L-glutamate in
      water at physiological pH values.
AB  - The interaction of the pyrazole-containing macrocyclic receptors
      3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]-octacosa
      1(27),11,14(28),24-tetraene 1[L1], 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26
      decaazatricyclo-[22.2.1.1(1)(1,14)]-octacosa-1(27),11,14(28),24-tetraene 2[L2],
      3,9,12,13,16,22,25,26-octaazatricyclo-[22.2.1.1(11,14)]-octacosa
      1(27),11,14(28),24-tetraene 3[L3], 6,19-dibenzyl-3,6,9,12,13,16,19,22,25,26
      decaazatricyclo-[22.2.1.1(11,)(14)]-octacosa-1(27),11,14(28),24-tetraene 4[L4],
      6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]
      octacosa-1(27),11,14(28),24-tetraene 5[L5], and 6,19-dioctyl
      3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]-octacosa
      1(27),11,14(28),24-tetraene 6[L6] with l-glutamate in aqueous solution has been
      studied by potentiometric techniques. The synthesis of receptors 3-6[L3-L6] is
      described for the first time. The potentiometric results show that 4[L4]
      containing benzyl groups in the central nitrogens of the polyamine side chains is
      the receptor displaying the larger interaction at pH 7.4 (Keff = 2.04 x 10(4)).
      The presence of phenethyl 5[L5] or octyl groups 6[L6] instead of benzyl groups
      4[L4] in the central nitrogens of the chains produces a drastic decrease in the
      stability [Keff = 3.51 x 10(2) (5), Keff = 3.64 x 10(2) (6)]. The studies show
      the relevance of the central polyaminic nitrogen in the interaction with
      glutamate. 1[L1] and 2[L2] with secondary nitrogens in this position present
      significantly larger interactions than 3[L3], which lacks an amino group in the
      center of the chains. The NMR and modeling studies suggest the important
      contribution of hydrogen bonding and pi-cation interaction to adduct formation.

PMID- 14733558
TI  - Enthalpies of formation of gas-phase N3, N3-, N5+, and N5- from Ab initio
      molecular orbital theory, stability predictions for N5(+)N3(-) and N5(+)N5(-),
      and experimental evidence for the instability of N5(+)N3(-).
AB  - Ab initio molecular orbital theory has been used to calculate accurate enthalpies
      of formation and adiabatic electron affinities or ionization potentials for N3,
      N3-, N5+, and N5- from total atomization energies. The calculated heats of
      formation of the gas-phase molecules/ions at 0 K are DeltaHf(N3(2Pi)) = 109.2,
      DeltaHf(N3-(1sigma+)) = 47.4, DeltaHf(N5-(1A1')) = 62.3, and DeltaHf(N5+(1A1)) =
      353.3 kcal/mol with an estimated error bar of +/-1 kcal/mol. For comparison
      purposes, the error in the calculated bond energy for N2 is 0.72 kcal/mol. Born
      Haber cycle calculations, using estimated lattice energies and the adiabatic
      ionization potentials of the anions and electron affinities of the cations,
      enable reliable stability predictions for the hypothetical N5(+)N3(-) and
      N5(+)N5(-) salts. The calculations show that neither salt can be stabilized and
      that both should decompose spontaneously into N3 radicals and N2. This conclusion
      was experimentally confirmed for the N5(+)N3(-) salt by low-temperature
      metathetical reactions between N5SbF6 and alkali metal azides in different
      solvents, resulting in violent reactions with spontaneous nitrogen evolution. It
      is emphasized that one needs to use adiabatic ionization potentials and electron
      affinities instead of vertical potentials and affinities for salt stability
      predictions when the formed radicals are not vibrationally stable. This is the
      case for the N5 radicals where the energy difference between vertical and
      adiabatic potentials amounts to about 100 kcal/mol per N5.

PMID- 14733559
TI  - Microwave spectroscopy measurements of rotational spectra and DFT calculations
      for two distinct structural isomers of 1,1'-dimethylferrocene.
AB  - Microwave spectra were obtained for two distinct structural isomers of 1,1'
      dimethylferrocene, an eclipsed synperiplanar isomer (phi = 0 degrees, the E0
      isomer), with A = 1176.9003(2) MHz, B = 898.3343(2) MHz, C = 668.7469(2) MHz, and
      an eclipsed synclinal isomer (phi = 72 degrees, the E72 isomer) with A =
      1208.7117(14) MHz, B = 806.4101(12) MHz, and C = 718.7179(8) MHz. The b-dipole,
      asymmetric-top spectra of both structural isomers were measured in the frequency
      range of 5-12 GHz using a Flygare-Balle type of spectrometer. A very good fit to
      observed transitions, with small distortion constants, was obtained for the E0
      conformer, indicating that this conformer is nearly rigid. The deviations
      obtained in a similar least-squares fit for the E72 confomer are significantly
      larger, indicating possible fluxional behavior for this conformer. In addition, 7
      out of the 26 transitions observed for the E72 isomer conformer clearly exhibit
      very small splittings, giving further evidence for internal motion. DFT
      calculations for the different possible conformations of 1,1'- dimethylferrocene
      arising from rotation of one methyl cyclopentadienyl ligand relative to the other
      about the nominal C5 axis by an angle phi (dihedral angle) were performed using
      the B3PW91 functional. The calculations converged and were optimized for five
      structures on this torsional potential energy surface corresponding to different
      dihedral angles phi; three yielded energy minima, and two gave energy maxima,
      corresponding to transition states. The experimental results are in very good
      agreement with the results of the DFT calculations.

PMID- 14733560
TI  - A general chemical route to polyaniline nanofibers.
AB  - Uniform polyaniline nanofibers readily form using interfacial polymerization
      without the need for templates or functional dopants. The average diameter of the
      nanofibers can be tuned from 30 nm using hydrochloric acid to 120 nm using
      perchloric acid as observed via both scanning and transmission electron
      microscopy. When camphorsulfonic acid is employed, 50 nm average diameter fibers
      form. The measured Brunauer-Emmett-Teller surface area of the nanofibers
      increases as the average diameter decreases. Further characterization including
      molecular weight, optical spectroscopy, and electrical conductivity are
      presented. Interfacial polymerization is shown to be readily scalable to produce
      bulk quantities of nanofibers.

PMID- 14733561
TI  - Crystal growth and structure determination of barium rhodates: stepping stones
      toward 2H-BaRhO3.
AB  - Single crystals of two new barium rhodates were grown from a molten potassium
      carbonate flux. The new rhodates, Ba(11)Rh(10)O(30) and Ba(32)Rh(29)O(87), are
      structurally related to the 2H-hexagonal perovskite structure and are
      characterized by pseudo one-dimensional chains of alternating face-sharing
      trigonal prisms and octahedra. The structures of Ba(11)Rh(10)O(30) and
      Ba(32)Rh(29)O(87) were solved using the 4D superspace group approach in Jana2000.
      Ba(11)Rh(10)O(30), with a repeat of nine RhO(6) octahedra followed by one RhO(6)
      trigonal prism, contains the longest chain sequence of face-sharing octahedra
      known for this 2H-perovskite related family of oxides. A structural analysis of
      these two compounds revealed clear trends in metal-metal distances and octahedral
      heights not previously identified for this family of oxides. The application of
      these trends toward the structure of the all-octahedra-containing end member of
      the structural series, the hypothetical 2H-BaRhO(3), enabled a prediction of its
      rhodium-rhodium distance, octahedral height, and lattice parameters.

PMID- 14733562
TI  - Facile synthesis and characterization of novel mesoporous and mesorelief oxides
      with gyroidal structures.
AB  - In this paper, we bring forward an effective strategy, solvothermal
      postsynthesis, to prepare ordered mesoporous silica materials with highly
      branched channels. Structural characterizations indicate that the titled
      mesoporous materials basically have the cubic double gyroidal (space group Ia-3d)
      structure with small fraction of distortions. The mesopore sizes and surface
      areas can be up to 8.8 nm and 540 m2/g, respectively, when microwave digestion is
      employed to remove the organic templates. A phase transition model is proposed,
      and possible explanations for the successful phase transition are elucidated. The
      results show that the flexible inorganic framework, high content of organic
      matrix, and nonpenetration of poly(ethylene oxide) segments may facilitate the
      structural evolution. This new synthetic strategy can also be extended to the
      preparation of other double gyroidal silica-based mesoporous materials, such as
      metal and nonmetal ions doped silica and organo-functionalized silica materials.
      The prepared 3D mesoporous silica can be further utilized to fabricate various
      ordered crystalline gyroidal metal oxide "negatives". The mesorelief "negatives"
      (Co3O4 and In2O3 are detailed here) prepared by impregnation and thermolysis
      procedures exhibit undisplaced, displaced, and uncoupled enantiomeric gyroidal
      subframeworks. It has been found that the amount of metal oxide precursors
      (hydrated metal nitrates) greatly influence the (sub)framework structure and
      single crystallinity of the mesorelief metal oxide particles. The single
      crystalline gyroidal metal oxides are ordered both at mesoscale and atomic scale.
      However, these orders are not commensurate with each other.

PMID- 14733563
TI  - Solvent-mediated folding of a doubly charged anion.
AB  - The microsolvation of the suberate dianion, -O2C(CH2)6CO2-, with two separate
      charge centers was studied by photoelectron spectroscopy and molecular dynamics
      simulation one solvent molecule at a time for up to 20 waters. It is shown that
      the two negative charges are solvated in the linear suberate alternately. As the
      solvent number increases, the negative charges are screened and a conformation
      change occurs at 16 waters, where the cooperative hydrogen bonding of water is
      large enough to overcome the Coulomb repulsion and pull the two negative charges
      closer through a water bridge. This conformation change, revealed both from the
      experiment and from the simulation, is a manifestation of the hydrophilic and
      hydrophobic forces at the molecular level.

PMID- 14733564
TI  - New heterogeneous polyoxometalate based mesoporous catalysts for hydrogen
      peroxide mediated oxidation reactions.
AB  - Inorganic-organic hybrid mesoporous materials were prepared by cocrystallization
      of a "sandwich" type polyoxometalate, [ZnWZn2(H2O)2(ZnW9O34)2]12-, and branched
      tripodal organic polyammonium salts, tris[2-(trimethylammonium)ethyl]-1,3,5
      benzenetricarboxylate or 1,3,5-tris[4-(N,N,N
      trimethylammoniumethylcarboxyl)phenyl]benzene trications. Scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM) showed formation of
      three-dimensional perforated coral-shaped amorphous materials with the organic
      cations surrounding polyoxometalate anions. N2 sorption analysis showed that the
      hybrid materials have a BET surface area of approximately 30-50 m2 g(-1) and an
      average pore diameter of 36 A leading to the classification of these materials as
      mesoporous materials with moderate surface areas. These hybrid materials behaved
      as very effective and selective heterogeneous catalysts for the epoxidation of
      allylic alcohols and oxidation of secondary alcohols to ketones with hydrogen
      peroxide as oxidant. The activity and selectivity of the heterogeneous catalysts
      based on the hybrid materials was similar to those of homogeneous catalysts based
      on the same [ZnWZn1(H2O)2(ZnW9O34)2]12- polyoxometalate.

PMID- 14733565
TI  - Hyponitrite radical, a stable adduct of nitric oxide and nitroxyl.
AB  - All major properties of the aqueous hyponitrite radicals (ONNO- and ONNOH), the
      adducts of nitric oxide (NO) and nitroxyl (3NO- and 1HNO), are revised. In this
      work, the radicals are produced by oxidation of various hyponitrite species in
      the 2-14 pH range with the OH, N3, or SO4- radicals. The estimated rate constants
      with OH are 4 x 10(7), 4.2 x 10(9), and 8.8 x 10(9) M(-1) s(-1) for oxidations of
      HONNOH, HONNO-, and ONNO2-, respectively. The rate constants for N3 + ONNO2- and
      SO4- + HONNO- are 1.1 x 10(9) and 6.4 x 10(8) M(-1) s(-1), respectively. The ONNO
      radical exhibits a strong characteristic absorption spectrum with maxima at 280
      and 420 nm (epsilon280 = 7.6 x 10(3) and epsilon420 = 1.2 x 10(3) M(-1) cm(-1)).
      This spectrum differs drastically from those reported, suggesting the radical
      misassignment in prior work. The ONNOH radical is weakly acidic; its pKa of 5.5
      is obtained from the spectral changes with pH. Both ONNO- and ONNOH are shown to
      be over 3 orders of magnitude more stable with respect to elimination of NO than
      it has been suggested previously. The aqueous thermodynamic properties of ONNO-
      and ONNOH radicals are derived by means of the gas-phase ab initio calculations,
      justified estimates for ONNOH hydration, and its pKa. The radicals are found to
      be both strongly oxidizing, E degrees (ONNO-/ONNO2-) = 0.96 V and E degrees
      (ONNOH, H+/HONNOH) = 1.75 V, and moderately reducing, E degrees (2NO/ONNO-) = 
      0.38 V and E degrees (2NO, H+/ONNOH) = -0.06 V, all vs NHE. Collectively, these
      properties make the hyponitrite radical an important intermediate in the aqueous
      redox chemistry leading to or originating from nitric oxide.

PMID- 14733566
TI  - On the mechanisms of oxidation of organic sulfides by H2O2 in aqueous solutions.
AB  - The mechanism of oxidation of organic sulfides in aqueous solutions by hydrogen
      peroxide was investigated via ab initio calculations. Specifically, two
      reactions, hydrogen transfer of hydrogen peroxide to form water oxide and the
      oxidation of dimethyl sulfide (DMS) by hydrogen peroxide to form dimethyl
      sulfoxide, were studied as models of these processes in general. Solvent effects
      are included both via including explicitly water molecules and via the
      polarizable continuum model. The former was found to have a much more significant
      effect than the latter. When explicit water molecules are included, a mechanism
      different from those proposed in the literature was found. Specific interactions
      including hydrogen bonding with 2-3 water molecules can provide enough
      stabilization for the charge separation of the activation complex. The energy
      barrier of the oxidation of DMS by hydrogen peroxide was estimated to be 12.7
      kcal/mol, within the experimental range of the oxidation of analogous compounds
      (10-20 kcal/mol). The major reaction coordinates of the reaction are the breaking
      of the O-O bond of H2O2 and the formation of the S-O bond, the transfer of
      hydrogen to the distal oxygen of hydrogen peroxide occurring after the system has
      passed the transition state. Reaction barriers of the hydrogen transfer of H2O2
      are an average of 10 kcal/mol or higher than the reaction barriers of the
      oxidation of DMS. Therefore, a two-step oxidation mechanism in which, first, the
      transfer of a hydrogen atom occurs to form water oxide and, second, the transfer
      of oxygen to the substrate occurs is unlikely to be correct. Our proposed
      oxidation mechanism does not suggest a pH dependence of oxidation rate within a
      moderate range around neutral pH (i.e., under conditions in which hydronium and
      hydroxide ions do not participate directly in the reaction), and it agrees with
      experimental observations over moderate pH values. Also, without including a
      protonated solvent molecule, it has activation energies that correspond to
      measured activation energies.

PMID- 14733567
TI  - Extreme projection of a proton into the pi-cloud of an aromatic ring: record
      shielding of an aromatic proton in trans-10b-methyl-10c-(1-naphthyl)-10b,10c
      dihydropyrene.
AB  - A synthetic sequence involving dithiametacyclophane --> metacyclophanediene -->
      dihydropyrene was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and
      trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene 5 and 6, respectively.
      Both exhibit a strong diamagnetic ring current despite the introduction of an
      internal bulky substituent within the pi-electron cloud. Their electronic spectra
      suggest interaction between the two near-perpendicular naphthyl and
      dihydropyrenyl pi systems, resulting in red shift and band broadening. All
      naphthyl protons are well resolved in their 1H NMR spectra due to a strong
      shielding effect of the dihydropyrene ring. The most shielded protons in 5 and 6
      are H1' and H2' at delta 2.47 and 1.42, respectively, being 5.25 and 5.95 ppm
      shifted from those of reference protons. There is evidence for free rotation on
      the NMR time scale of the 2-naphthyl ring in 5 with a preference for a particular
      conformer, whereas the 1-naphthyl ring in 6 is conformationally rigid with its
      H2' projecting deeply into the pi-cloud, thus accounting for the most shielded
      aromatic proton (H2' in 6) reported to date.

PMID- 14733568
TI  - Reversible voltage-induced assembly of au nanoparticles at liquid/liquid
      interfaces.
AB  - The voltage-induced assembly of mercaptosuccinic acid-stabilized Au nanoparticles
      of 1.5 +/- 0.4 nm diameter is investigated at the polarizable water/1,2
      dichloroethane interface. Admittance measurements and quasi-elastic laser
      scattering (QELS) studies reveal that the surface concentration of the
      nanoparticle at the liquid/liquid boundary is reversibly controlled by the
      applied bias potential. The electrochemical and optical measurements provide no
      evidence of irreversible aggregation or deposition of the particles at the
      interface. Analysis of the electrocapillary curves constructed from the
      dependence of the frequency of the capillary waves on the applied potential and
      bulk particle concentration indicates that the maximum particle surface density
      is 3.8 x 10(13) cm(-2), which corresponds to 67% of a square closed-pack
      arrangement. This system provides a unique example of reversible assembly of
      nanostructures at interfaces, in which the density can be effectively tuned by
      the applied potential bias.

PMID- 14733569
TI  - Theoretical study of the trapping of the OOH radical by coenzyme Q.
AB  - The reactivity of the hydroperoxyl radical with coenzyme Q, as a prototypical
      chemical reaction involved in biological antioxidant actions, was studied
      theoretically. Two pathways were analyzed: the hydrogen abstraction reaction from
      the phenolic hydrogen on the reduced form (ubiquinol), and OOH addition on the
      oxidized form (ubiquinone). Optimized geometries, harmonic vibrational
      frequencies, and energies of the stationary points (reactants, intermediate
      complexes, transition states, and products) for each pathway were calculated at
      the BHandHLYP/6-31G level of theory. The reaction paths for the two mechanisms
      were traced independently, and the respective thermal rate constants were
      calculated using variational transition-state theory with multidimensional small
      curvature tunneling. We found that the reactivity of the OOH radical is dominated
      by the hydrogen abstraction mechanism on ubiquinol, with a rate constant of 5.32
      x 10(5) M(-1) s(-1), at 298 K. This result strongly contrasts with that, also
      obtained by our group, for the more reactive OH radical, which attacks ubiquinone
      by an addition mechanism, with a diffusion-controlled rate of 6.25 x 10(10) M(-1)
      s(-1), at 298 K.

PMID- 14733570
TI  - Quantitative analysis of conformational exchange contributions to 1H-15N multiple
      quantum relaxation using field-dependent measurements. Time scale and structural
      characterization of exchange in a calmodulin C-terminal domain mutant.
AB  - Multiple-quantum spin relaxation is a sensitive probe for correlated
      conformational exchange dynamics on microsecond to millisecond time scales in
      biomolecules. We measured differential 1H-15N multiple-quantum relaxation rates
      for the backbone amide groups of the E140Q mutant of the C-terminal domain of
      calmodulin at three static magnetic field strengths. The differential multiple
      quantum relaxation rates range between -88.7 and 92.7 s(-1), and the mean and
      standard deviation are 7.0 +/- 24 s(-1), at a static magnetic field strength of
      14.1 T. Together with values of the 1H and 15N chemical shift anisotropies (CSA)
      determined separately, the field-dependent data enable separation of the
      different contributions from dipolar-dipolar, CSA-CSA, and conformational
      exchange cross-correlated relaxation mechanisms to the differential multiple
      quantum relaxation rates. The procedure yields precise quantitative information
      on the dominant conformational exchange contributions observed in this protein.
      The field-dependent differences between double- and zero-quantum relaxation rates
      directly benchmark the rates of conformational exchange, showing that these are
      fast on the chemical shift time scale for the large majority of residues in the
      protein. Further analysis of the differential 1H-15N multiple-quantum relaxation
      rates using previously determined exchange rate constants and populations,
      obtained from 15N off-resonance rotating-frame relaxation data, enables
      extraction of the product of the chemical shift differences between the resonance
      frequencies of the 1H and 15N spins in the exchanging conformations,
      deltasigma(H)deltasigma(N). Thus, information on the 1H chemical shift
      differences is obtained, while circumventing complications associated with direct
      measurements of conformational exchange effects on 1H single-quantum coherences
      in nondeuterated proteins. The method significantly increases the information
      content available for structural interpretation of the conformational exchange
      process, partly because deltasigma(H)deltasigma(N) is a signed quantity, and
      partly because two chemical shifts are probed simultaneously. The present results
      support the hypothesis that the exchange in the calcium-loaded state of the E140Q
      mutant involves conformations similar to those of the wild-type apo (closed) and
      calcium-loaded (open) states.

PMID- 14733571
TI  - Computational elucidation of the transition state shape selectivity phenomenon.
AB  - The most commonly cited example of a transition state shape selective reaction, m
      xylene disproportionation in zeolites, is examined to determine if the local
      spatial environment of a reaction can significantly alter selectivity. In the
      studied reaction, ZPE-corrected rate limiting energy barriers are 136 kJ/mol for
      the methoxide-mediated pathway and 109 to 145 kJ/mol for the diphenylmethane
      mediated pathway. Both pathways are likely to contribute to selectivity and
      disfavor one product isomer (1,3,5-trimethylbenzene), but relative selectivity to
      the other two isomers varies with pore geometry, mechanistic pathway, and
      inclusion of entropic effects. Most importantly, study of one pathway in three
      different common zeolite framework types (FAU, MFI, and MOR) allows explicit and
      practically oriented consideration of pore shape. Variation of the environment
      shape at the critical transition states is thus shown to affect the course of
      reaction. Barrier height shifts on the order of 10-20 kJ/mol are achievable.
      Observed selectivities do not agree with the transition state characteristics
      calculated here and, hence, are most likely due to product shape selectivity.
      Further examination of the pathways highlights the importance of mechanistic
      steps that do not result in isomer-defining bonds and leads to a more robust
      definition of transition state shape selectivity.

PMID- 14733573
TI  - Modeling the structure of amorphous MoS3: a neutron diffraction and reverse Monte
      Carlo study.
AB  - A model for the structure of amorphous molybdenum trisulfide, a-MoS3, has been
      created using reverse Monte Carlo methods. This model, which consists of chains
      of MoS6 units sharing three sulfurs with each of its two neighbors and forming
      alternate long, nonbonded, and short, bonded, Mo-Mo separations, is a good fit to
      the neutron diffraction data and is chemically and physically realistic. The
      paper identifies the limitations of previous models based on Mo3 triangular
      clusters in accounting for the available experimental data.

PMID- 14733572
TI  - Band-selective carbonyl to aliphatic side chain 13C-13C distance measurements in
      U-13C,15N-labeled solid peptides by magic angle spinning NMR.
AB  - We describe three-dimensional magic angle spinning NMR experiments that enable
      simultaneous band-selective measurement of the multiple distance constraints
      between carbonyl and side chain carbons in uniformly 13C,15N-labeled peptides.
      The approaches are designed to circumvent the dipolar truncation and to allow
      experimental separation of the multiple quantum (MQ) relaxation and dipolar
      effects. The pulse sequences employ the double quantum (DQ) rotational resonance
      in the tilted frame (R2TR) to perform selective polarization transfers that
      reintroduce the 13C'-13Cgamma,delta dipolar interactions. The scheme avoids
      recoupling of the strongly coupled C'-Calpha and C'-Cbeta spin pairs, therefore
      minimizing dipolar truncation effects. The experiment is performed in a constant
      time fashion as a function of the radio frequency irradiation intensity and
      measures the line shape of the DQ transition. The width and the intensity of this
      line shape are analyzed in terms of the DQ relaxation and dipolar coupling. The
      attenuation of the multispin effects in the presence of relaxation enables a two
      spin approximation to be employed for the analysis of the experimental data. The
      systematic error introduced by this approximation is estimated by comparing the
      results with a three-spin simulation. The contributions of B1-inhomogeneity, CSA
      orientation effects, and the effects of inhomogeneous line broadening are also
      estimated. The experiments are demonstrated in model U-13C,15N-labeled peptides,
      N-acetyl-L-Val-L-Leu and N-formyl-L-Met-L-Leu-L-Phe, where 10 and 6 distances,
      ranging between 3 and 6 A, were measured, respectively.

PMID- 14733574
TI  - Experimental and theoretical investigation of the 13C and 15N chemical shift
      tensors in melanostatin-exploring the chemical shift tensor as a structural
      probe.
AB  - The determination of backbone conformations in powdered peptides using 13C and
      15N shift tensor information is explored. The 13C and 15N principal shift values
      in natural abundance 13C and 15N melanostatin (L-Pro-L-Leu-Gly amide) are
      measured using the FIREMAT technique. Furthermore, the orientation of the C-N
      bond in the 13C shift principal axis system for the backbone carbons is obtained
      from the presence of the 13C-14N dipolar coupling. The Ramachandran angles for
      the title compound are obtained from solid-state NMR data by comparing the
      experimentally determined shift tensor information to systematic theoretical
      shielding calculations on N-formyl-L-amino acid-amide models. The effects of
      geometry optimization and neglect of intermolecular interactions on the
      theoretical shielding values in the model compounds are investigated. The sets of
      NMR derived Ramachandran angles are assembled in a set of test structures that
      are compared to the available single-crystal X-ray structure. Shift tensor
      calculations on the test structures and the X-ray structure are used to further
      assess the importance of intermolecular interactions when the shift tensor is
      used as a structural probe in powdered peptides.

PMID- 14733576
TI  - Element-coded affinity tags for peptides and proteins.
AB  - Isotope-coded affinity tags (ICAT) represent an important new tool for the
      analysis of complex mixtures of proteins in living systems [Aebersold, R., and
      Mann, M. (2003) Nature, 422, 198-207]. We envisage an alternative protein
      labeling technique based on tagging with different element-coded metal chelates,
      which affords affinity chromatography, quantification, and identification of a
      tagged peptide from a complex mixture. As proof of concept, a synthetic peptide
      was modified at a cysteine side chain with either a carboxymethyl group or
      acetamidobenzyl-1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid
      (AcBD) chelates of terbium or yttrium. A mixture of the three modified peptides
      in a mole ratio of 100:1.0:0.83 carboxymethyl:AcBD-Tb:AcBD-Y was trypsinized,
      purified on a new affinity column that binds rare-earth DOTA chelates, and
      analyzed by LC-MS/MS. Chelate-tagged tryptic peptides eluted cleanly from the
      affinity column; the tagged peptides chromatographically coeluted during LC-MS
      analysis, were present in the expected ratio as indicated by MS ion intensity,
      and were sequence-identified by tandem mass spectrometry. DOTA-rare earth
      chelates have exceptional properties for use as affinity tags. They are highly
      polar and water-soluble. Many of the rare earth elements are naturally
      monoisotopic, providing a variety of simple choices for preparing mass tags.
      Further, the rare earths are heavy elements, whose mass defects give the masses
      of tagged peptides exact values not normally shared by molecules that contain
      only light elements.

PMID- 14733577
TI  - N-(3-Trifluoroethanesulfonyloxypropyl)anthraquinone- 2-carboxamide: a new
      heterobifunctional reagent for immobilization of biomolecules on a variety of
      polymer surfaces.
AB  - A new heterobifunctional reagent, N-(3
      trifluoroethanesulfonyloxypropyl)anthraquinone-2-carboxamide (NTPAC) has been
      developed, useful for making bioconjugates and immobilization of biomolecules,
      viz., oligonucleotides, peptides, proteins, etc., on a variety of carbon
      containing solid surfaces. Its trifluoroethanesulfonate ester group reacts with
      aminoalkyl or mercaptoalkyl functions present in biomolecules, and the
      anthraquinone structure reacts with a variety of carbon-containing polymers under
      ultraviolet irradiation (365 nm). The reagent has been used in two ways. First,
      the reagent, NTPAC, was first brought in contact with the above said supports and
      exposed to long wavelength ultraviolet light (365 nm), thereby generating active
      trifluoroethanesulfonate ester functions on the support, which subsequently react
      with appropriate mercaptoalkyl- or aminoalkyl-containing biomolecules to fix them
      on the supports. In another route, the proposed reagent was allowed to react
      first with proteins or 5'-aminoalkyl- or mercaptoalkyl-modified oligonucleotides
      to form the appropriate biomolecule-anthraquinone conjugate, which was then
      brought in contact with a variety of carbon-containing polymers, viz., modified
      controlled pore glass (CPG), modified glass microslides, cross-linked
      polystyrene, nylon, cross-linked polysaccharides, polypropylene (PP),
      polyethylene (PE), etc., and exposed to long wavelength ultraviolet light (365
      nm), resulting in immobilization of the conjugates on the support. Both of the
      routes work satisfactorily and we could successfully immobilize a number of
      enzymes and modified oligonucleotides on a variety of supports.

PMID- 14733578
TI  - Hybrid nanoparticles based on organized protein immobilization on fullerenes.
AB  - Nanoscale carbon materials (i.e., fullerenes and nanotubes) are an attractive
      platform for applications in biotransformations and biosensors. The interesting
      properties displayed by nanoparticles demand new strategies for the manipulation
      of these materials on the nanoscale. Controlled modification of their surface
      with biomolecules is required to fully realize their potential in
      bionanotechnology. In this work, immobilization of a fullerene derivative with a
      mutant subtilisin is demonstrated, and the effect of the fullerene on the protein
      activity is determined. The fullerene-conjugated enzyme had improved catalytic
      properties in comparison to subtilisin immobilized on nonporous silica. Further,
      the pH profile of free and fullerene-conjugated subtilisin were almost identical.

PMID- 14733579
TI  - Production of soluble ScFvs with C-terminal-free thiol for site-specific
      conjugation or stable dimeric ScFvs on demand.
AB  - ScFv recombinant antibody fragments can provide specific tumor binding modules
      for targeting drugs. In the process of building multimeric tumor targeting
      pharmaceuticals, a prerequisite is the conservation of functional scFv antigen
      binding domains, thereby excluding scFv random conjugation to a carrier molecule
      or to another scFv. The pCANTAB 5E phage display/expression vector was
      genetically engineered to express any scFv gene as scFv with an additional C
      terminal cysteine (scFv-Cys) such that the specific conjugation site is removed
      from the binding domain. Selected scFvs derived from an anti-MUC-1 scFv phage
      library were expressed in pCANTAB 5E and its modified version pCANTAB 5E Cys
      vectors, and compared for key characteristics. Production yields of scFv and scFv
      Cys in shaker flask and biofermentor were compared. In the absence of a reducing
      agent, stable dimers (covalent scFv homodimers (scFv-Cys)2) were the major form
      of scFv-Cys. These diabodies provided substantial signal enhancement for
      immunohistochemical staining of tissues. In the presence of a reducing agent,
      scFv-Cys molecules remained monomeric, with the free SH available for conjugation
      to a PEG(maleimide)2 scaffold to form immunoreactive PEG(scFv)2 bioconjugates.
      ScFv expression from pCANTAB 5E Cys allowed for the production of soluble scFv
      Cys protein from E.coli, either as stable scFv-Cys or (scFv-Cys)2. ScFv-Cys can
      be used for conjugation to PEG to form bivalent PEG (scFv-Cys)2 molecules or used
      as (scFv-Cys)2 for increased sensitivity in IHC.

PMID- 14733580
TI  - Effect of limited solid-state glycation on the conformation of lysozyme by ESI
      MSMS peptide mapping and molecular modeling.
AB  - Although protein glycation has been implicated in the alteration of protein
      functionality, both in vivo (in biological systems) and in vitro (in food
      systems), the effect of the protein-bound glycan moiety on the
      structure/conformation of proteins that result in the modification of
      functionality is not clear. In this article, we report a study of the
      conformational changes of glycated lysozyme using LC-ESI-MSMS peptide mapping,
      and molecular modeling. A comparison of the RP-HPLC of the tryptic digests of
      unglycated and glycated lysozyme showed markedly different chromatographic
      profiles. Analysis of the peptide composition of the chromatographic fractions of
      the tryptic digests revealed that glycation of lysozyme resulted in the
      modification of its conformation. Glycation-induced changes in the conformation
      of lysozyme resulted in the exposure of its active site region to increased
      proteolytic activity of trypsin. Molecular simulation of triglycated lysozyme
      also showed that limited glycation of lysozyme caused reorientation of the active
      site residues (Arg 45, Arg 68, Asn 44, and Trp 62) and increased solvent
      accessibility into the active site region of the protein. The results of the
      modeling experiment corroborated the results of the RP-HPLC and ESI-MSMS peptide
      mapping.

PMID- 14733581
TI  - Liposomes with differential lipid components exert differential adjuvanticity in
      antigen-liposome conjugates via differential recognition by macrophages.
AB  - We previously reported that liposomes having differential lipid components
      displayed differential adjuvant effects when antigen was coupled with liposomes
      via glutaraldehyde. In the present study, antigen-liposome conjugates prepared
      using liposomes having differential lipid components were added to the macrophage
      culture, and phagocytosis and the antigen digest of liposome-coupled antigen by
      macrophages were then investigated. Antigen presentation by macrophages to an
      antigen-specific T-cell clone was further investigated using the same conjugates.
      Antigen-liposome conjugates which induced higher levels of antibody production in
      vivo were recognized more often, and the liposome-coupled antigen was digested to
      a greater degree by macrophages than antigen-liposome conjugates which induced
      lower levels of antibody production. These results correlated closely with those
      regarding antigen presentation by macrophages; when antigen was coupled to
      liposomes showing higher adjuvant effect, macrophages cocultured with antigen
      liposome conjugates activated antigen-specific T-cells at a higher degree. The
      concentration of OVA in the macrophage culture added as antigen-liposome
      conjugates was approximately 32 microg/mL. However, the extent of T-cell
      activation was almost equal to that when 800 microg/mL of soluble OVA was added
      to the culture. The results of the present study demonstrated that the adjuvant
      activity of liposomes observed primary in vivo correlated closely with the
      recognition of antigen-liposome conjugates and antigen presentation of liposome
      coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes
      are exerted at the beginning of the immune response, i.e., recognition of antigen
      by antigen-presenting cells.

PMID- 14733582
TI  - MicroPET and autoradiographic imaging of breast cancer alpha v-integrin
      expression using 18F- and 64Cu-labeled RGD peptide.
AB  - Cell adhesion molecules alphavbeta3 and alphavbeta5 play a pivotal role in tumor
      angiogenesis and metastasis. Antiangiogenic therapy by using small peptide
      antagonists of alphav-integrins slows tumor growth and prevents tumor spread. The
      ability to visualize and quantify integrin expression will enable selection of
      appropriate patients for clinical trials, following determination of treatment
      efficacy and development of new potent drugs. We have previously labeled cyclic
      RGD peptide c(RGDyK) with 125I and 18F and applied the radiotracers to both
      subcutaneous and orthotopic brain tumor models. Here we conjugated c(RGDyK) with
      1,4,7,10-tetraaza-1,4,7,10-tetradodecane-N,N',N' ',N' "-tetraacetic acid (DOTA)
      and labeled the DOTA-RGD conjugate with 64Cu (t1/2) = 12.8 h, 19% beta+) in high
      radiochemical purity and specific activity. The tumor targeting ability and in
      vivo kinetics of 64Cu-DOTA-RGD was compared with [18F]FB-RGD and 125I-RGD in
      orthotopic MDA-MB-435 breast cancer model. All three radiotracers revealed fast
      blood clearance and high tumor-to-blood and tumor-to-muscle ratios. 125I-RGD had
      higher tumor uptake than the corresponding 18F and 64Cu analogues. [18F]FB-RGD
      indicated a fast tumor washout rate and an unfavorable hepatobiliary excretion
      pathway, resulting in significant activity accumulation in gallbladder and
      intestines. 64Cu-DOTA-RGD had prolonged tumor retention (1.44 +/- 0.09 %ID/g at 4
      h postinjection) and persistent uptake in the liver. All three tracers revealed
      receptor specific tumor accumulation which were illustrated by effective blocking
      via coinjection with a blocking dose of c(RGDyK). Static microPET imaging and
      whole-body autoradiography showed strong contrast from the contralateral
      background. In conclusion, overall molecular charge and characteristics of
      radiolabels have profound effects on tumor accumulation and in vivo kinetics of
      radiolabeled RGD peptide. Further modification of the RGD peptide and
      optimization of the tracer for prolonged tumor uptake and improved in vivo
      kinetics are being explored.

PMID- 14733583
TI  - Nanogels for oligonucleotide delivery to the brain.
AB  - Systemic delivery of oligonucleotides (ODN) to the central nervous system is
      needed for development of therapeutic and diagnostic modalities for treatment of
      neurodegenerative disorders. Macromolecules injected in blood are poorly
      transported across the blood-brain barrier (BBB) and rapidly cleared from
      circulation. In this work we propose a novel system for ODN delivery to the brain
      based on nanoscale network of cross-linked poly(ethylene glycol) and
      polyethylenimine ("nanogel"). The methods of synthesis of nanogel and its
      modification with specific targeting molecules are described. Nanogels can bind
      and encapsulate spontaneously negatively charged ODN, resulting in formation of
      stable aqueous dispersion of polyelectrolyte complex with particle sizes less
      than 100 nm. Using polarized monolayers of bovine brain microvessel endothelial
      cells as an in vitro model this study demonstrates that ODN incorporated in
      nanogel formulations can be effectively transported across the BBB. The transport
      efficacy is further increased when the surface of the nanogel is modified with
      transferrin or insulin. Importantly the ODN is transported across the brain
      microvessel cells through the transcellular pathway; after transport, ODN remains
      mostly incorporated in the nanogel and ODN displays little degradation compared
      to the free ODN. Using mouse model for biodistribution studies in vivo, this work
      demonstrated that as a result of incorporation into nanogel 1 h after intravenous
      injection the accumulation of a phosphorothioate ODN in the brain increases by
      over 15 fold while in liver and spleen decreases by 2-fold compared to the free
      ODN. Overall, this study suggests that nanogel is a promising system for delivery
      of ODN to the brain.

PMID- 14733584
TI  - [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation
      dose estimates.
AB  - It has been demonstrated in various murine tumor models that radiolabeled RGD
      peptides can be used for noninvasive determination of alphavbeta3 integrin
      expression. Introduction of sugar moieties improved the pharmacokinetic
      properties of these peptides and led to tracer with good tumor-to-background
      ratios. Here we describe the synthesis, radiolabeling, and the metabolic
      stability of a glycosylated RGD-peptide ([18F]Galacto-RGD) and give first
      radiation dose estimates for this tracer. The peptide was assembled on a solid
      support using Fmoc-protocols and cyclized under high dilution conditions. It was
      conjugated with a sugar amino acid, which can be synthesized via a four-step
      synthesis starting from pentaacetyl-protected galactose. For radiolabeling of the
      glycopeptide, 4-nitrophenyl-2-[18F]fluoropropionate was used. This prosthetic
      group allowed synthesis of [18F]Galacto-RGD with a maximum decay-corrected
      radiochemical yield of up to 85% and radiochemical purity >98%. The overall
      radiochemical yield was 29 +/- 5% with a total reaction time including final HPLC
      preparation of 200 +/- 18 min. The metabolic stability of [18F]Galacto-RGD was
      determined in mouse blood and liver, kidney, and tumor homogenates 2 h after
      tracer injection. The average fraction of intact tracer in these organs was
      approximately 87%, 76%, 69%, and 87%, respectively, indicating high in vivo
      stability of the radiolabeled glycopeptide. The expected radiation dose to humans
      after injection of [18F]Galacto-RGD has been estimated on the basis of dynamic
      PET studies with New Zealand white rabbits. According to the residence times in
      these animals the effective dose was calculated using the MIRDOSE 3.0 program as
      2.2 x 10(-2) mGy/MBq. In conclusion, [18F]Galacto-RGD can be synthesized in high
      radiochemical yields and radiochemical purity. Despite the time-consuming
      synthesis of the prosthetic group 185 MBq of [18F]Galacto-RGD, a sufficient dose
      for patient studies, can be produced starting with approximately 2.2 GBq of
      [18F]flouride. Moreover, the fast excretion, the suitable metabolic stability and
      the low estimated radiation dose allow to evaluate this tracer in human studies.

PMID- 14733585
TI  - Structure property analysis of pentamethine indocyanine dyes: identification of a
      new dye for life science applications.
AB  - A collection of nine pentamethine indocyanine dyes was synthesized, and the
      photophysical characteristics relevant to applications in cell biology and single
      molecule detection were analyzed in detail. Substituents at the aromatic system
      covering the auxochromic series and substitutions in the polymethine chain were
      investigated with respect to absorption and emission spectra, fluorescence
      lifetimes, fluorescence quantum yields, and fluorescence autocorrelations.
      Substitutions in the polymethine chain increased the nonradiative energy
      dissipation of the excited singlet state and decreased the fluorescence quantum
      yield, relative to the unsubstituted compound. For substituents at the aromatic
      rings the fluorescence quantum yield negatively correlates with the position of
      the substituents in the auxochromic series -SO(3)(-), -H, -F, -CH(3). Compounds
      with sulfonic acid groups or halogen atoms attached to the indolenine systems had
      the highest fluorescence quantum yields. The compound S0387 had nearly 70% of the
      quantum yield of Cy5 and comparable photostability. The free carboxylic acid of
      S0387 was attached to peptides in high yield and purity by established procedures
      of solid-phase synthesis. The dye-labeled peptides did not aggregate or bind to
      tissue culture cells and proteins unspecifically. The indocyanine dye S0387 is
      therefore an attractive new fluorophore for in vitro and cell-based detection of
      receptor ligand interaction at nanomolar concentrations by flow cytometry,
      fluorescence correlation spectroscopy, and laser scanning microscopy.

PMID- 14733586
TI  - Noninvasive imaging of quantum dots in mice.
AB  - Quantum dots having four different surface coatings were tested for use in in
      vivo imaging. Localization was successfully monitored by fluorescence imaging of
      living animals, by necropsy, by frozen tissue sections for optical microscopy,
      and by electron microscopy, on scales ranging from centimeters to nanometers,
      using only quantum dots for detection. Circulating half-lives were found to be
      less than 12 min for amphiphilic poly(acrylic acid), short-chain (750 Da) methoxy
      PEG or long-chain (3400 Da) carboxy-PEG quantum dots, but approximately 70 min
      for long-chain (5000 Da) methoxy-PEG quantum dots. Surface coatings also
      determined the in vivo localization of the quantum dots. Long-term experiments
      demonstrated that these quantum dots remain fluorescent after at least four
      months in vivo.

PMID- 14733587
TI  - Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein
      carbohydrate recognition using purified plant and mammalian lectins and wild-type
      and lectin-gene-transfected tumor cells as targets.
AB  - Multivalent glycoclusters have the potential to become pharmaceuticals by virtue
      of their target specificity toward clinically relevant sugar receptors. Their
      application can also provide fundamental insights into the impact of two spatial
      factors on binding, i.e., topologies of ligand (branching mode, cluster
      presentation) and carbohydrate recognition domains in lectins. Persubstituted
      macrocycles derived from nucleophilic substitution of iodide from heptakis 6
      deoxy-6-iodo-beta-cyclodextrin by the unprotected sodium thiolate of 3-(3
      thioacetyl propionamido)propyl glycosides (galactose, lactose and N
      acetyllactosamine) were prepared. The produced glycoclusters were first tested as
      competitive inhibitors in solid-phase assays. A plant toxin from mistletoe and an
      immunoglobulin G fraction from human serum were markedly susceptible. A nearly
      400-fold increase in inhibitory potency of each galactose moiety in the
      heptavalent form relative to free lactose (217-fold relative to free galactose)
      was detected. Thus, these glycoclusters can efficiently interfere, for example,
      with xenoantigen-dependent hyperacute rejection. Among the tested galectins
      selected from this family of adhesion- and growth-regulatory endogenous lectins,
      the substituted beta-cyclodextrins acted as sensors to delineate topological
      differences between the two dimeric prototype proteins. The relatively strong
      reactivity with chimera-type galectin-3, a mediator of tumor metastasis,
      disclosed selectivity for glycocluster binding among galectins. Equally
      important, the geometry of ligand display (maxiclusters, bi- or triantennary N
      glycans) made its mark on the inhibitory potency. To further determine the
      sensitivity of a distinct galectin presented on the cell surface and not in
      solution, we established a stably transfected tumor cell clone. We detected a
      significant response to presence of the multivalent inhibitor. This type of
      chemical scaffold with favorable pharmacologic properties might thus be exploited
      for the design of galectin- and ligand-type-selective glycoclusters.

PMID- 14733588
TI  - Synthesis and physicochemical characterization of Gd-DTPA-B(sLex)A, a new MRI
      contrast agent targeted to inflammation.
AB  - A new magnetic resonance imaging (MRI) contrast agent designed to mimic sialyl
      Lewis X (sLeX) and to target inflammation has been synthesized and characterized.
      The evolution of its proton longitudinal relaxivity as a function of the magnetic
      field (NMRD) and temperature has been studied. The exchange rate of the water
      coordinated to the metal has been assessed by oxygen-17 relaxometry. The
      transmetalation by zinc(II) ions and the noncovalent binding to human serum
      albumin have been evaluated. The results show no limitation by the residence time
      of the coordinated water molecule above room temperature, a higher stability of
      the complex versus transmetalation by zinc(II) ions than a parent complex, the
      clinically used Gd-DTPA-BMA, and negligible interaction with human serum albumin.

PMID- 14733590
TI  - A comparative study of different presentation strategies for an HIV peptide
      immunogen.
AB  - Different strategies have been used to increase the immunogenicity of an
      antigenic HIV peptide as a vaccine candidate. The selected B-cell epitope
      comprises 15 amino acids (317-331) of the V3 region of HIV-1, JY1 isolate
      (subtype D), in tandem with a T-helper epitope corresponding to the 830-844
      region of tetanus toxoid. Several presentations, including oligomerization,
      multiple antigenic peptide dendrimers, and conjugation to dextran beads or to
      other macromolecular carriers, have been synthesized and evaluated. Murine sera
      from the different presentations of the V3 epitope have been compared with regard
      to antibody titers and cross-reactivity with heterologous HIV subtypes. The
      dendrimer version of the peptide conjugated to HBsAg protein was a better
      immunogen than the dendrimer alone and showed a higher immunogenicity than other
      multimeric presentations or than the peptide alone conjugated to dextran. The
      dendrimer version, either alone or conjugated to HBSAg, enhanced cross-reactivity
      toward heterologous V3 sequences relative to monomeric peptide. In addition, fine
      epitope mapping of the entire JY1 sequence by sera from the different
      immunization groups was performed by the spot synthesis technique. Results showed
      that the amino acids involved in molecular recognition were LXQXXY or LXQXLY,
      with particularly strong recognition of the C-terminal region LGQALY. However,
      cross-reactivity toward the heterologous sequences did not completely correlate
      with recognition of particular amino acids in the primary sequences. These
      results can find application in the development of HIV vaccine candidates.

PMID- 14733589
TI  - Potential and practical adrenomedullary PET radiopharmaceuticals as an
      alternative to m-iodobenzylguanidine: m-(omega-[18F]fluoroalkyl)benzylguanidines.
AB  - To investigate adrenomedullary radiopharmaceuticals for positron emission
      tomography (PET), we have developed no-carrier-added m-(omega
      [18F]fluoroalkyl)benzylguanidines. m-(omega-[18F]Fluoroalkyl)benzylguanidines
      were prepared in two steps starting from N,N'-bis(tert-butyloxycarbonyl)-N' '
      (omega-methanesulfonyloxyalkyl)benzylguanidines in 20-30% radiochemical yields
      (decay corrected for 100 min) and with high radiochemical purity (>97%) and shown
      to be stable (>90%) in an in vitro metabolic stability assay. The binding of m-(3
      [18F]fluoropropyl)benzylguanidine ((18F]3) to SK-N-SH human neuroblastoma cells
      was temperature dependent, and binding levels at 4 degrees C were reduced to half
      of that at 37 degrees C, which was similar to the reduction rate observed for
      [123I]MIBG. Tissue distribution studies in mice showed the highest uptake in the
      adrenals (%ID/g = 27.2 +/- 5.0%) with relatively high uptake in the myocardium
      (%ID/g = 9.3 +/- 0.5%). The results suggest that this radiotracer holds promise
      as a useful adrenomedullary radiopharmaceutical for PET imaging.

PMID- 14733591
TI  - 8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for
      evaluation of medium chain fatty acid metabolism in the liver.
AB  - 8-Cyclopentadienyltricarbonyl 99mTc 8-oxooctanoic acid (99mTc-CpTTOA; 1a) was
      synthesized for evaluation of medium chain fatty acid metabolism in the liver.
      99mTc-CpTTOA was prepared in high radiochemical yield (50-63%) by a double ligand
      transfer reaction of methyl 8-ferrocenyl-8-oxooctanoate and Na99mTcO4 in the
      presence of CrCl3 and Cr(CO)6, followed by hydrolysis. This radiotracer was shown
      to be stable (>90% at 6 h) when incubated with human serum. Aqueous extraction of
      the radioactivity from the liver and blood samples of mice suggested that 99mTc
      CpTTOA was mainly metabolized via beta-oxidation in the liver, and the
      radioactivity was retained longer in CCl4-treated mice than in control mice,
      possibly due to impaired beta-oxidation in the former. Planar images of rats
      injected with 99mTc-CpTTOA showed accumulation of the radioactivity in the liver,
      kidneys, and bladder with rapid hepatic clearance as a function of time. Analysis
      of the metabolites from the liver and urine samples of rats further supported
      that 99mTc-CpTTOA was metabolized to 4-cyclopentadienyltricarbonyl 99mTc 4
      oxobutanoic acid (99mTc-CpTTBA; 1c) via beta-oxidation. The results suggested
      that this radiotracer might be of valuable use in the evaluation of fatty acid
      metabolism in the liver.

PMID- 14733592
TI  - A new strategy for the preparation of peptide-targeted radiopharmaceuticals based
      on an fmoc-lysine-derived single amino acid chelate (SAAC). automated solid-phase
      synthesis, NMR characterization, and in vitro screening of fMLF(SAAC)G and
      fMLF[(SAAC-Re(CO)3)+]G.
AB  - A tridentate single amino acid chelate (SAAC) derived from N-alpha-Fmoc-l-lysine
      was incorporated within a short peptide sequence using an automated peptide
      synthesizer. Novel derivatives of the chemotactic peptide fMLF were prepared such
      that the SAAC and its Re complex were selectively placed between a terminal
      glycine amino acid and the targeting fMLF sequence. The products, which were
      synthesized in parallel, were characterized by mass spectrometry and multi-NMR
      spectroscopy. The latter technique demonstrated that the structures of the
      targeting portions of the peptides are the same in the SAAC and Re-SAAC
      derivatives. The affinities of the reported compounds for the formyl peptide
      receptor were subsequently determined using flow cytometry and were found to be
      comparable to that of the parent peptide. The results of this work demonstrate
      the feasibility and numerous benefits of using the SAAC system to prepare peptide
      targeted Tc(I) and Re(I) radiopharmaceuticals.

PMID- 14733593
TI  - Synthesis, characterization, and evaluation of ferrocene-theophylline conjugates
      for use in electrochemical enzyme immunoassay.
AB  - A series of 8-(ferrocenylalkyl)theophylline conjugates were synthesized for
      evaluation in a homogeneous, competitive electrochemical immunoassay for
      theophylline with amperometric detection of the ferrocene label at +320 mV. The
      electrical signal was amplified via redox cycling with the glucose
      oxidase/glucose system. The resulting catalytic current was strongly inhibited
      upon binding of the conjugates to anti-theophylline antibodies such that a large
      excess of theophylline was required to achieve complete reversal leading to an
      assay with poor sensitivity in the clinical range. A study of the nonspecific
      interaction of the antibodies with various ferrocene derivatives indicated that
      this was reduced when a charged functional group was present on the metallocene
      ring. Consequently, a conjugate was synthesized with a quaternary ammonium group
      which when incorporated into the assay resulted in improved sensitivity.

PMID- 14733594
TI  - A glycopolymer chaperone for fibroblast growth factor-2.
AB  - Mono- and disaccharide-containing glycopolymers were synthesized by cyanoxyl
      mediated polymerization of acrylamide with acrylate-derivatized mono- and
      disaccharides. We demonstrate that a glycopolymer bearing pendant, fully sulfated
      lactose units effectively replaces heparin and heparan sulfate as a molecular
      chaperone for fibroblast growth factor-2 (FGF-2). Specifically, a compound was
      identified that protects FGF-2 from proteolytic, acid, and heat-induced
      degradation, while selectively promoting growth factor and receptor dimerization.
      Significantly, the capacity of this heparin-mimic to promote an FGF-2 specific
      proliferative cell response was confirmed and suggests potential applications for
      this compound and related derivatives in areas related to therapeutic
      angiogenesis.

PMID- 14733595
TI  - Factors influencing the ability of nuclear localization sequence peptides to
      enhance nonviral gene delivery.
AB  - Nonviral gene delivery is limited by inefficient transfer of DNA from the
      cytoplasm to the nucleus. Nuclear localization sequence (NLS) peptides have been
      widely used to exploit intracellular transport mechanisms and promote nuclear
      uptake of DNA. However, the exact conditions to successfully utilize the
      properties of NLS peptides are still unclear. In the present study a panel of NLS
      peptides that bind different transport receptors were compared for their ability
      to enhance nonviral gene transfer. Several factors such as method of
      incorporating the NLS peptide, type of NLS peptide, DNA morphology, and proper
      characterization of NLS peptide/DNA conjugates were identified as important
      considerations in utilizing NLS peptides to enhance gene transfer. In particular,
      it was shown that a peptide derived from human T cell leukaemia virus type 1
      (HTLV) was able to effectively condense DNA into discrete particles and mediate
      levels of transgene expression up to 32-fold greater than polylysine-based
      polyplexes. This is the first study to demonstrate efficient transfection
      mediated by an importin beta-binding peptide based on the HTLV sequence.
      Promising results were also achieved with a 7-fold increase in gene expression
      using a NLS peptide/DNA conjugate formed by site-specific linkage of an extended
      SV40 peptide via a peptide nucleic acid (PNA) clamp. Altogether, the results from
      this study should help to define the requirements for successful NLS-enhanced
      transfection.

PMID- 14733596
TI  - Dendritic polyglycerol sulfates as new heparin analogues and potent inhibitors of
      the complement system.
AB  - Due to several limitations of heparin, a widely used antithrombotic drug, there
      is large interest to develop alternatives. The aim of the presented study was to
      produce fully synthetic highly branched heparin mimetics. For this purpose, a new
      type of 'treelike' polysulfated polymers based on dendritic polyglycerol was
      synthesized. An efficient synthetic approach has been chosen to prepare several
      polyglycerol sulfates with different molecular weights as well as a polyglycerol
      carboxylate analogue and to evaluate them for their anticoagulant and
      anticomplementary activities. In contrast to the nonderivatized and the
      carboxylated polyglycerols, the polyglycerol sulfates prolong the activated
      partial thromboplastin time (APTT) and thrombin time (TT) and inhibit both the
      classical (CCA) and alternative complement activation (ACA). Whereas their
      anticoagulant activity in the APTT and in the TT amounts to 5.7-8.1% and 15.7
      33.6%, respectively, of that of unfractionated heparin (UFH), their CCA and ACA
      inhibitory activity is 13.4-23.9 and 2.7-3.7 times, respectively, higher. In
      contrast to sulfated polysaccharides, the activities are not clearly dependent on
      the molecular weight, which might be due to the globular 3D-structure of the
      dendritic molecules. Due to the coherence between coagulation, complement
      activation and inflammation in the pathophysiology of numerous diseases,
      polyglycerol sulfates with both anticoagulant and anticomplementary activities
      represent promising candidates for the development of potential drugs.

PMID- 14733597
TI  - Synthesis and characterization of hapten-protein conjugates for antibody
      production against small molecules.
AB  - For the generation of antibodies against small hapten molecules, the hapten is
      cross-linked with some carrier protein to make it immunogenic. However, the
      formation of such conjugates is not always reproducible. This may lead to
      inconsistent hapten-protein stoichiometries, resulting in large variations in the
      generation of the desired antibodies. In the study described here the hapten
      (mercaptopropionic acid derivative of atrazine) was coupled to carrier protein at
      five different molar ratios. The hapten-protein conjugates prepared were
      characterized thoroughly by spectrophotometric absorption, fluorescence, matrix
      assisted laser desorption ionization (MALDI), and gel electrophoresis methods,
      before being used for the immunization and assay purposes. Electrophoresis and
      fluorescence methods were very useful in detecting hapten-protein cross-linking
      while MALDI-MS and spectrophotometric detection provided qualitatively comparable
      hapten density. The production of specific antibodies was sought following the
      generation of appropriate hapten-protein conjugates. A high antibody titer with
      moderate antibody specificity was obtained with hapten density around 15
      molecules per carrier protein. The study proved useful for monitoring the course
      of hapten-protein conjugation for the production of specific antibodies against
      small molecules.

PMID- 14733598
TI  - Preparation of azacrown-functionalized 2'-O-methyl oligoribonucleotides,
      potential artificial RNases.
AB  - An improved synthesis for 3-(3-aminopropyl)- and 3-(3-mercaptopropyl)-1,5,9
      triazacyclododecane has been developed and alternative methods for their
      conjugation to oligonucleotides have been described. Accordingly, the 3
      aminopropyl azacrown and its N-(3-aminopropanoyl)-3-aminopropyl analogue have
      been tethered to the 3'-terminus of a 2'-O-methyloligoribonucleotide by
      aminolytic cleavage of the thioester linker utilized for the chain assembly.
      Studies on a monomeric model compound verify that the reaction proceeds solely by
      the attack of the primary amino group. 5'-Conjugation has been achieved by
      introducing a 2-benzylthio-2-oxoethyl group to the 5'-terminus as a
      phosphoramidite reagent and cleaving the thioester bond with the 3-aminopropyl
      azacrown. For intrachain conjugation, a phosphoramidite reagent derived from 1
      deoxy-1-(2-benzylthio-2-oxoethyl)-beta-d-erythro-pentofuranose has been inserted
      in a desired position within the chain and subjected to on-support aminolysis
      with the 3-aminopropyl azacrown or its N-(3-aminopropanoyl)-3-aminopropyl and N
      (6-aminohexanoyl)-3-aminopropyl analogues. The 3-mercaptopropyl-derivatized
      azacrown has been tetherd by a disulfide bond to a 3'-(3-mercaptoalkyl)phosphate
      tailed oligonucleotide. The 3'- and intrachain-tethered conjugates have been
      shown to cleave as their Zn(II) chelate complementary oligoribonucleotide
      sequences.

PMID- 14733599
TI  - Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor
      monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential
      delivery agent for neutron capture therapy.
AB  - The gene encoding EGFR often is amplified in human gliomas, and the receptor
      itself has been considered as a potential target for the specific delivery of
      therapeutic agents to brain tumors. The purpose of the present study was to
      investigate the use of the chimeric MoAb cetuximab (IMC-C225), which is directed
      against EGFR and EGFRvIII, as a boron delivery agent for neutron capture therapy
      (NCT) of brain tumors. As determined by 125I-cetuximab radioligand binding
      assays, F98 rat glioma cells, which had been transfected with the gene encoding
      EGFR (F98EGFR), expressed 1.60 +/- 0.13 x 10(5) receptor sites/cell with a Ka =
      1.64 +/- 0.32 x 10(8) M-1). F98 cells transfected with the gene encoding a mutant
      form of EGFR, designated the F98EGFRvIII glioma, expressed 1.07 +/- 0.10 x 10(5)
      receptor sites/cell with a Ka = 2.18 +/- 0.54 x 10(9) M-1 compared to background
      levels expressed on F98 wild-type cells (F98WT). A heavily boronated, fifth
      generation polyamidoamine (PAMAM or "starburst") dendrimer, G5-B1100, was linked
      to oligosaccharide moieties, which were distant from antigen binding sites of
      cetuximab, by means of the heterobifunctional reagents N-succinimidyl 3-(2
      pyridyldithio)propionate (SPDP) and N-(k-maleimidoundecanoic acid) hydrazide
      (KMUH). The resulting bioconjugate, designated C225-G5-B1100, was separated from
      the unconjugated dendrimer using a Sephacryl S-300 column. On the basis of the
      relative concentration ratios of boron and protein, there were approximately 1100
      boron atoms per molecule of cetuximab with only a slight reduction of Ka. The
      localization of C225-G5-B1100 or G5-B1100 in rats bearing intracerebral implants
      of either F98EGFR or F98WT gliomas was determined 24 h following direct
      intratumoral (i.t.) injection at which time 92.3 +/- 23.3 micrograms B/g tumor
      was localized in F98EGFR gliomas versus 36.5 +/- 18.8 micrograms B/g tumor in
      F98WT gliomas and 13.4 +/- 6.1 micrograms in normal brain. In contrast, only 6.7
      +/- 3.6 micrograms B/g tumor of G5-B1100 was localized in F98EGFR gliomas
      following i.t. injection, thereby demonstrating specific molecular targeting of
      EGFR. Based on these data, BNCT studies will be initiated in F98EGFR glioma
      bearing rats to evaluate C225-G5-B1100 for the treatment of intracerebral brain
      tumors.

PMID- 14733600
TI  - Preparation of no-carrier-added technetium-99m complexes via metal-assisted
      cleavage from a solid phase.
AB  - A novel method for the preparation of no-carrier-added (nca) complexes
      [99mTc(CO)3L] (L = diethylenetriamine or picolylamine-N-acetic acid) is
      described. The ligands were covalently bound to a solid support of organic
      polymers via formation of a tertiary amine from the chelating unit. This C-N bond
      to the solid phase is selectively cleaved during the formation of the technetium
      complexes by intramolecular nucleophilic attack of a remaining hydroxy ligand to
      the alpha-carbon. The complex [99mTc(CO)3L] is released into solution while
      uncomplexed ligand and uncleaved complex remain solid-phase bound. High specific
      activity technetium complexes can then be isolated by simple filtration. Cleavage
      yield depends on temperature, pH, and ligand. Up to 50% release from the solid
      phase could be achieved under optimized conditions. Corresponding to the 99mTc
      concentration, free ligand is present in concentrations lower than 10(-7) M. If a
      targeting vector is conjugated to these ligands, no-carrier-added
      radiopharmaceuticals can be prepared in that way.

PMID- 14733602
TI  - Efficient synthesis of isotopically pure isotope-coded affinity tagging reagents.
AB  - Synthesis of an isotopically pure d8-ICAT linker, N-[(5,5,6,6,8,8,9,9-2H)-13
      biotinamido-4,7,10-trioxatridecanyl] tert-butyloxy carbamide (12), has been
      achieved in seven steps with an overall yield of 33%. Conjugation of exchange
      inert d4-starting materials by classic etherification reaction yielded a pure
      synthon, carrying eight deuteriums that remained exchange-inert throughout
      subsequent reactions. This modified synthesis constitutes a significant
      improvement to the reported syntheses of "heavy" ICAT reagent in terms of
      expense, yield, and isotopic retention. This synthesis is easily adapted to
      incorporate additional deuterium atoms and is equally applicable for
      incorporation of either 13C and/or 18O. In addition, this synthesis allows for
      the introduction of different orthogonal functionalities and provides for a high
      yielding series of differentially encoded ICAT tags.

PMID- 14733601
TI  - Reagents for astatination of biomolecules: comparison of the in vivo distribution
      and stability of some radioiodinated/astatinated benzamidyl and nido-carboranyl
      compounds.
AB  - An investigation has been conducted to assess the in vivo stability of a series
      of astatinated benzamides and astatinated nido-carborane compounds in mice. It
      was hypothesized that the higher bond strength of boron-astatine bonds in the
      nido-carboranes might provide increased stability toward in vivo deastatination.
      Four tri-n-butylstannylbenzamides were prepared for radiohalogenation and
      evaluation in vivo. Those compounds were N-propyl-4-(tri-n-butylstannyl)benzamide
      1a, N-propyl-3-(tri-n-butylstannyl)benzamide 2a, ethyl 4-tri-n
      butylstannylhippurate 3a, and 4-tri-n-butylstannyl-hippuric acid 4a. Seven mono
      nido-carboranyl derivatives were prepared for radiohalogenation and in vivo
      evaluation. Four of the seven mono-carboranyl derivatives (5a, 6a, 7a, 13a)
      contained a 3-(nido-carboranyl)propionamide functionality, and the remaining
      compounds (8a, 8g, 10a) contained a 4-(nido-carboranyl)aniline functionality. Two
      additional derivatives (11a, 12a) were prepared that contained bis-(nido
      carboranylmethyl)benzene moieties (also referred to as Venus flytrap complexes
      (VFCs). All benzamide and nido-carborane compounds underwent facile iodination
      and radiohalogenation, except a 4-(nido-carboranyl)aniline derivative, 8a.
      Iodination of 8a resulted in a mixture, of which the desired iodinated product
      was a minor component. Therefore, radiohalogenation was not attempted. It is
      believed that the mixture of products is due to the presence of a thiourea bond.
      Previous studies have shown that thiourea bonds can interfere with halogenation
      reactions. In vivo comparisons of the compounds were conducted by co-injection of
      dual labeled (125/131I and 211At) compounds. Tissue distribution data were
      obtained at 1 and 4 h postinjection of the radiolabeled compounds, as that was
      sufficient to determine if astatine was being released. Stability of the
      astatinated compound was assessed by the difference in concentration of
      radioiodine and astatine in lung and spleen. All of the benzamides were found to
      undergo rapid deastatination in vivo. The nido-carborane derivatives appeared to
      be slightly more stable to in vivo deastatination; however, they had long blood
      residence times. The surprising finding was that the VFC derivatives did not
      release 211At in vivo, even though they rapidly localized to liver. This finding
      provides encouragement that stable conjugates of 211At may be attained if
      appropriate modifications of the VFC can be made to redirect their excretion
      through the renal system.

PMID- 14733603
TI  - Novel strategies for the prevention of bypass graft failure.
AB  - Bypass vein graft disease remains a significant limitation to the care of
      millions of patients with ischemic disease of the heart and lower extremities.
      The pathogenesis of this rapid, aggressive, occlusive disease lies in the
      remodeling response of the grafts themselves to the new arterial environment. As
      such, the molecular and cellular biology of neointimal hyperplasia provides a
      unique opportunity for cardiovascular researchers to more closely model a human
      clinical entity from its inception to the development of advanced disease. Recent
      years have therefore seen a broad new array of possible interventions for vein
      graft disease based on a sophisticated translation of genetic and molecular
      science. One of these applications, E2F decoys, has already progressed to phase
      III clinical studies, and many others will likely follow as the tools for
      therapeutic translation continue to improve. These include both gene transfer and
      gene blockade strategies.

PMID- 14733604
TI  - Proinflammatory cytokines in the treatment of bacterial and fungal infections.
AB  - Mortality due to severe bacterial infections has not been markedly effected by
      the introduction of new antimicrobial drugs over the last 30-40 years. This has
      emphasized the need for development of new therapeutic strategies to combat
      sepsis. The outcome of an infection depends on two factors: the growth of the
      microorganisms (including the effect of antibacterial drugs), and the host's
      defensive response to the invading organism. It is known that injection of
      bacterial products into experimental animals leads to enhanced nonspecific
      resistance to a variety of microorganisms. The discovery of the specific
      mediators responsible for modulation of host defense has created new
      possibilities for the development of alternative treatment strategies. Molecules
      such as interleukins, interferons, tumor necrosis factors and hematopoietic
      growth factors have become available in recombinant form, and their therapeutic
      potential in various infectious diseases has been tested in various experimental
      models of infections. Initial data in various patient groups indicate that
      adjunctive therapy with recombinant proinflammatory cytokines may have beneficial
      effects in the treatment of bacterial and fungal infections.

PMID- 14733605
TI  - Cytokines as therapeutic targets for osteoarthritis.
AB  - Osteoarthritis (OA) is a debilitating, progressive disease of diarthrodial joints
      associated with the aging process. With the exception of anti-inflammatory
      corticosteroids and nonsteroidal anti-inflammatory drugs which inhibit cyclo
      oxygenase-2, the enzyme responsible for prostaglandin biosynthesis in
      inflammation, no specific therapy based on fundamental intracellular pathways of
      chondrocytes and synoviocytes exists for the medical management of OA. At the
      molecular level, OA is characterized by an imbalance between chondrocyte
      anabolism and catabolism. Disruption of chondrocyte homeostasis primarily affects
      the cartilage extracellular matrix (ECM), which is responsible for the
      biomechanical properties of the tissue. Recent evidence has implicated cytokines,
      among which interleukin (IL)-1, tumor necrosis factor-alpha, IL-6, and IL-17 seem
      most involved in the OA process of cartilage destruction. The primary role of
      these cytokines is to modulate the expression of matrix metalloproteinases and
      cartilage ECM proteins. Cartilage repair that could restore the functional
      integrity of the joint is also impaired because chondrocytes in OA cartilage
      appear unable to respond to insulin-like growth factor-1 or respond abnormally to
      transforming growth factor-beta. As these growth factors also modulate cytokine
      expression, they may prove useful in designing strategies for suppressing
      'chondrocyte activation'. Although cytokines and growth factors provide a
      potential therapeutic target for OA, it will be necessary to elucidate the
      fundamental mechanisms that cytokines employ to cause chondrocyte and synoviocyte
      dysfunction before 'anti-cytokine' therapy can be employed in the medical
      management of the disease.

PMID- 14733606
TI  - A multi-model approach to nucleic acid-based drug development.
AB  - With the advent of functional genomics and the shift of interest towards sequence
      based therapeutics, the past decades have witnessed intense research efforts on
      nucleic acid-mediated gene regulation technologies. Today, RNA interference is
      emerging as a groundbreaking discovery, holding promise for development of
      genetic modulators of unprecedented potency. Twenty-five years after the
      discovery of antisense RNA and ribozymes, gene control therapeutics are still
      facing developmental difficulties, with only one US FDA-approved antisense drug
      currently available in the clinic. Limited predictability of target site
      selection models is recognized as one major stumbling block that is shared by all
      of the so-called complementary technologies, slowing the progress towards a
      commercial product. Currently employed in vitro systems for target site selection
      include RNAse H-based mapping, antisense oligonucleotide microarrays, and
      functional screening approaches using libraries of catalysts with randomized
      target-binding arms to identify optimal ribozyme/DNAzyme cleavage sites.
      Individually, each strategy has its drawbacks from a drug development
      perspective. Utilization of message-modulating sequences as therapeutic agents
      requires that their action on a given target transcript meets criteria of potency
      and selectivity in the natural physiological environment. In addition to sequence
      dependent characteristics, other factors will influence annealing reactions and
      duplex stability, as well as nucleic acid-mediated catalysis. Parallel
      consideration of physiological selection systems thus appears essential for
      screening for nucleic acid compounds proposed for therapeutic applications.
      Cellular message-targeting studies face issues relating to efficient nucleic acid
      delivery and appropriate analysis of response. For reliability and simplicity,
      prokaryotic systems can provide a rapid and cost-effective means of studying
      message targeting under pseudo-cellular conditions, but such approaches also have
      limitations. To streamline nucleic acid drug discovery, we propose a multi-model
      strategy integrating high-throughput-adapted bacterial screening, followed by
      reporter-based and/or natural cellular models and potentially also in vitro
      assays for characterization of the most promising candidate sequences, before
      final in vivo testing.

PMID- 14733607
TI  - Expression systems for the production of recombinant pharmaceuticals.
AB  - The new generation of biological products are largely the result of genetic
      engineering. The qualitative and quantitative demand for recombinant proteins is
      steadily increasing. Molecular biologists are constantly challenged by the need
      to improve and optimise the existing expression systems, and also develop novel
      approaches to face the demands of producing the complex proteins of tomorrow.
      This continuous evolution is paralleled by growing concerns about the safety of
      these novel pharmaceuticals, with health authorities setting high standards for
      certification. One of the strategies used by researchers in this field involves
      sourcing new genetic elements for incorporation into expression systems by
      systematically analysing the rich natural diversity of microorganisms and plant
      based expression systems. There are, in addition, numerous tools for modifying
      microorganisms and for re-engineering existing biological pathways or processes
      to meet the needs of the pharmaceutical industry. The aim of this review is to
      present the conventional and alternative expression systems, focusing on
      prokaryotic expression systems and briefly exploring other complementary
      recombinant protein production systems and their unique features.

PMID- 14733608
TI  - Intravenous immunoglobulin plus interferon-alpha in autoimmune hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) may be associated with a variety of
      autoimmune phenomena causing a therapeutic dilemma for treatment with interferon
      alpha (IFNalpha), which stimulates autoimmune symptoms, or with corticosteroids,
      which may lead to an increasing of viral load. To evaluate the possible role of
      intravenous immunoglobulins (IVIg) in the response of patients treated with
      IFNalpha, we administered IVIg plus IFNalpha and compared the results with a
      group of patients treated with IFNalpha alone. METHODS: Forty-two patients
      affected by chronic hepatitis C with probable autoimmune disease were eligible
      for this open-label, randomised study. All patients tested positively for anti
      nuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal
      antibodies and anti-mitochondrial antibodies. Patients were randomly assigned to
      one of two groups: group A received IVIg at a dosage of 400 mg/kg each day for 5
      days, and then 3 MUI of leucocyte IFNalpha three times a week, while group B
      received physiological solution followed by the administration of leucocyte
      IFNalpha three times a week at the same dosage for 6 months. Complete biochemical
      response was defined as a sustained normalisation of alanine aminotransferase
      levels, and complete virological response was defined as complete clearance of
      virus throughout the entire 6-month follow-up period. Immunological response was
      measured in terms of Autoimmune Hepatitis (AIH) score, while histological
      response was based on a reduction in histological activity index (HAI) score.
      RESULTS: Compared with patients receiving IFNalpha alone, a higher percentage of
      patients who received IFNalpha plus IVIg showed complete virological and
      histological responses (p = 0.04). More patients in the combination therapy group
      achieved biochemical and immunological responses, although the differences
      between the groups were not statistically significant at all time points.
      CONCLUSIONS: Exogenously added Ig might modulate the immune network at various
      points. We propose that the immunomodulating action of IVIg acts synergistically
      with IFNalpha, achieving a better response to IFN treatment in patients with
      chronic HCV associated with autoimmunity. Data obtained from this preliminary
      study indicate a positive prospective for the clinical use of gamma globulins in
      patients with a high probability of autoimmune disorders associated with HCV
      infection.

PMID- 14733609
TI  - Flow cytometric evaluation of leukocyte function in rat whole blood.
AB  - The aim of this study was to establish a standard flow cytometric method to
      measure the phagocytic function of and intracellular hydrogen peroxide (H2O2)
      production by rat leukocytes. Thirty-six adult, male Sprague-Dawley rats were
      included in this study. Whole-blood specimens from the inferior vena cava were
      collected in a heparinized tube and ethylenediaminetetraacetic acid (EDTA)
      anticoagulated tube. The phagocytic function of and intracellular H2O2 generation
      by leukocytes were measured with FACS Vantage trade mark flow cytometer (Becton
      Dickinson, San Jose, CA), using fluorescent microspheres and dihydrorhodamine-123
      as probes, respectively. Several conditions were optimized in this study,
      including anticoagulants (heparin and EDTA), fluorescent probes (0.75- and 1.72
      microm-diameter microspheres), incubation time, and concentration of the
      chemicals used in the experiment. Neutrophils, monocytes, and lymphocytes could
      be clearly defined and separated in whole blood by flow cytometry and tested for
      phagocytosis and intracellular H2O2 generation without the need for further
      purification and handling of the cells. Intracellular H2O2 production by and
      phagocytic function of neutrophils and monocytes were inhibited in EDTA
      anticoagulated blood compared with heparin- anticoagulated blood (P < 0.01).
      Neutrophils showed similar phagocytic function to 0.75- and 1.72-microm
      microspheres, but monocytes showed weak phagocytic activity to 1.72-microm beads
      compared with 0.75-microm beads (P < 0.01). In conclusion, a flow cytometric
      method to measure the phagocytic function of and intracellular H2O2 production by
      rat leukocytes has been developed. Quantitative flow cytometric analysis of rat
      leukocyte function is convenient and feasible and provides a reliable and rapid
      assay to assess phagocytosis and intracellular H2O2 production by rat neutrophils
      and monocytes.

PMID- 14733610
TI  - Strategies to reduce oxidative stress in cardiovascular disease.
AB  - A multitude of studies in experimental animals, together with clinical data,
      provide evidence that increased production of ROS (reactive oxygen species) are
      involved in the development and progression of cardiovascular disease. As ROS
      appear to have a critical role in atherosclerosis, there has been considerable
      interest in identifying the enzyme systems involved and in developing strategies
      to reduce oxidative stress. Prospective clinical trials with vitamins and hormone
      replacement therapy have not fulfilled earlier promises, although there is still
      interest in other dietary supplements. Superoxide dismutase mimetics, thiols,
      xanthine oxidase and NAD(P)H oxidase inhibitors are currently receiving much
      interest, while animal studies using gene therapy show promise, but are still at
      an early stage. Of the drugs in common clinical use, there is evidence that ACE
      (angiotensin-converting enzyme) inhibitors and AT1 (angiotensin II type 1)
      receptor blockers have beneficial effects on oxidative stress above their
      antihypertensive properties, whereas statins, in addition to improving lipid
      profiles, may also lower oxidative stress.

PMID- 14733611
TI  - pH-dependent autocleavage of lambda repressor occurs in the operator-bound form:
      characterization of lambda repressor autocleavage.
AB  - The first-order rate constants for the RecA-independent, spontaneous, pH
      dependent autocleavage of the lambda cI repressor was measured in the present
      study at pH 10.6 at 27, 37 and 42 degrees C respectively. Autocleavage of the
      repressor occurs also at pH 9 and 8, although at progressively slower rates. We
      demonstrate that the spontaneous autocleavage occurs also in the operator-bound
      state, at a rate either higher than or equal to the rate in solution, depending
      on the pH value. Owing to the near equality of the rate constant in both operator
      free and operator-bound repressors, it can be inferred that the cleavage site has
      a similar structure and dynamics with respect to the catalytic site in both forms
      at neutral pH. Covalent modification using PMSF, brought about by a large molar
      excess of the reagent, inhibits autocleavage of the lambda repressor. The
      difficulty in obtaining this covalent modification is rationalized using our
      recent lambda repressor models. Bimolecular type II trans -cleavage was observed
      previously for mutant LexA repressors lacking a crucial catalytic serine or
      lysine residue [Kim and Little (1993) Cell (Cambridge, Mass.) 73, 1165-1173], but
      it could still be cleaved by an 85-202 'enzyme' fragment possessing an improved
      or hypercleavable character lacking its own cleavage site. Such a type II trans 
      cleavage was not observed with the covalently modified intact lambda repressor
      used as substrate and the purified wild-type lambda repressor 112-236 fragment
      used as the 'enzyme'. All these results show that for the wild-type lambda
      repressor, the catalytic site is close to the cleavage site in both operator-free
      and -bound states. In the lytic pathway, the repressor is mainly cleaved via RecA
      mediated cleavage, which occurs much faster than the spontaneous autocleavage;
      the possible biological significance of this slow, spontaneous, but constant,
      autocleavage is related to the lysogenic state, when RecA-mediated cleavage is
      absent.

PMID- 14733612
TI  - Interactions of histatin 5 and histatin 5-derived peptides with liposome
      membranes: surface effects, translocation and permeabilization.
AB  - A number of cationic antimicrobial peptides, among which are histatin 5 and the
      derived peptides dhvar4 and dhvar5, enter their target cells and interact with
      internal organelles. There still are questions about the mechanisms by which
      antimicrobial peptides translocate across the membrane. We used a liposome model
      to study membrane binding, translocation and membrane-perturbing capacities of
      histatin 5, dhvar4 and dhvar5. Despite the differences in amphipathic characters
      of these peptides, they bound equally well to liposomes, whereas their membrane
      activities differed remarkably: dhvar4 translocated at the fastest rate, followed
      by dhvar5, whereas the histatin 5 translocation rate was much lower. The same
      pattern was seen for the extent of calcein release: highest with dhvar4, less
      with dhvar5 and almost none with histatin 5. The translocation and disruptive
      actions of dhvar5 did not seem to be coupled, because translocation occurred on a
      much longer timescale than calcein release, which ended within a few minutes. We
      conclude that peptide translocation can occur through peptide-phospholipid
      interactions, and that this is a possible mechanism by which antimicrobial
      peptides enter cells. However, the translocation rate was much lower in this
      model membrane system than that seen in yeast cells. Thus it is likely that, at
      least for some peptides, additional features promoting the translocation across
      biological membranes are involved as well.

PMID- 14733613
TI  - Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid
      signalling pathways promote pancreatic exocrine gene expression in mouse
      embryonic stem cells.
AB  - Extracellular signalling cues play a major role in the activation of
      differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and
      can differentiate into a wide variety of specialized cells. Recently, protocols
      designed to induce endocrine pancreatic differentiation in vitro have been
      designed but little information is currently available concerning the potential
      of ES cells to differentiate into acinar pancreatic cells. By using conditioned
      media of cultured foetal pancreatic rudiments, we demonstrate that ES cells can
      respond in vitro to signalling pathways involved in exocrine development and
      differentiation. In particular, modulation of the hedgehog, transforming growth
      factor beta, retinoid, and fibroblast growth factor pathways in ES cell-derived
      embryoid bodies (EB) resulted in increased levels of transcripts encoding
      pancreatic transcription factors and cytodifferentiation markers, as demonstrated
      by RT-PCR. In EB undergoing spontaneous differentiation, expression of the
      majority of the acinar genes (i.e. amylase, carboxypeptidase A and elastase) was
      induced after the expression of endocrine genes, as occurs in vivo during
      development. These data indicate that ES cells can undergo exocrine pancreatic
      differentiation with a kinetic pattern of expression reminiscent of pancreas
      development in vivo and that ES cells can be coaxed to express an acinar
      phenotype by activation of signalling pathways known to play a role in pancreatic
      development and differentiation.

PMID- 14733614
TI  - Signalling activity of beta-catenin targeted to different subcellular
      compartments.
AB  - Beta-catenin plays a dual role as an adhesion molecule in adherens junctions at
      the plasma membrane and as a key intermediate in the canonical Wnt signalling
      pathway. The cytosolic soluble pool of beta-catenin, involved in the transmission
      of the Wnt signal, is normally subjected to rapid protein degradation. On
      activation of the Wnt cascade, beta-catenin becomes stabilized and then
      translocates into the nucleus where it co-activates transcription factors of the
      TCF (T-cell factor)/LEF (lymphoid enhancer factor) family. The expression of
      plasma membrane-targeted forms of beta-catenin has been shown to also activate
      TCF/LEF-dependent transcription and different mechanisms have been put forward.
      In the present study, we have undertaken a systematic analysis of the signalling
      capability of non-degradable forms of beta-catenin targeted to different cellular
      compartments. beta-Catenin targeted to the plasma membrane activated
      transcription to a greater extent compared with non-targeted beta-catenin, and
      led to a marked stabilization of cytosolic soluble beta-catenin. These effects
      were independent of the competition with endogenous beta-catenin for binding to E
      cadherin at the plasma membrane, since targeting non-degradable beta-catenin to
      other cellular compartments, i.e. the outer mitochondrial membrane and the
      endoplasmic reticulum membrane, also resulted in the accumulation of cytosolic
      wild-type beta-catenin and activation of beta-catenin-dependent signalling. In
      contrast, nuclear-targeted beta-catenin was without significant effect on
      cytosolic wild-type beta-catenin and did not activate transcription. Our results
      suggest that cytosolic accumulation of beta-catenin is a prerequisite for the
      activation of TCF/LEF-dependent transcription in the nucleus.

PMID- 14733617
TI  - The site of origin of the 1918 influenza pandemic and its public health
      implications.

PMID- 14733615
TI  - Elucidation of eukaryotic elongation factor-2 contact sites within the catalytic
      domain of Pseudomonas aeruginosa exotoxin A.
AB  - Pseudomonas aeruginosa produces the virulence factor, ETA (exotoxin A), which
      catalyses an ADP-ribosyltransferase reaction of its target protein, eEF2
      (eukaryotic elongation factor-2). Currently, this protein-protein interaction is
      poorly characterized and this study was aimed at identifying the contact sites
      between eEF2 and the catalytic domain of ETA (PE24H, an ETA from P. aeruginosa, a
      24 kDa C-terminal fragment containing a His6 tag). Single-cysteine residues were
      introduced into the toxin at 21 defined surface-exposed sites and labelled with
      the fluorophore, IAEDANS [5-(2-iodoacetylaminoethylamino)-1-napthalenesulphonic
      acid]. Fluorescence quenching studies using acrylamide, and fluorescence lifetime
      and wavelength emission maxima analyses were conducted in the presence and
      absence of eEF2. Large changes in the microenvironment of the AEDANS [5-(2
      aminoethylamino)-1-naphthalenesulphonic acid] probe after eEF2 binding were not
      observed as dictated by both fluorescence lifetime and wavelength emission maxima
      values. This supported the proposed minimal contact model, which suggests that
      only small, discrete contacts occur between these proteins. As dictated by the
      bimolecular quenching constant (k(q)) for acrylamide, binding of eEF2 with toxin
      caused the greatest change in acrylamide accessibility (>50%) when the
      fluorescence label was near the active site or was located within a known
      catalytic loop. All mutant proteins showed a decrease in accessibility to
      acrylamide once eEF2 bound, although the relative change varied for each labelled
      protein. From these data, a low-resolution model of the toxin-eEF2 complex was
      constructed based on the minimal contact model with the intention of enhancing
      our knowledge on the mode of inactivation of the ribosome translocase by the
      Pseudomonas toxin.

PMID- 14733618
TI  - Composition of the editorial boards of leading medical education journals.
AB  - BACKGROUND: Researchers from the developing world contribute only a limited
      proportion to the total research output published in leading medical education
      journals. Some of them believe that there is a substantial editorial bias against
      their work. To obtain an objective basis for further discussion the present study
      was designed to assess the composition of the editorial boards of leading medical
      education journals. METHODS: The editorial boards of the three leading medical
      education journals according to their impact factor were retrieved from the
      respective January issue of the year 2003. We evaluated in which countries the
      editorial board members were based and classified these countries using the World
      Bank income criteria. RESULTS: Individuals from a number of countries can be
      found on the editorial boards of the investigated journals, but most of them are
      based in high-income countries. CONCLUSION: The percentage of editorial board
      members which are based in developing world countries is higher for the leading
      medical education journals than in most of their psychiatry and general medicine
      counterparts. But it is still too low.

PMID- 14733620
TI  - Pulmonary rehabilitation for chronic obstructive pulmonary disease: a scientific
      and political agenda.
AB  - Pulmonary rehabilitation (PR) is the standard of care for patients suffering
      chronic obstructive pulmonary disease (COPD). This report describes and defines
      PR and reviews the evidence regarding the efficacy of PR. COPD management
      guidelines that include PR have been published by the European Respiratory
      Society, the American Thoracic Society, and the British Thoracic Society, and
      those guidelines were supported by evidence-based guidelines published jointly by
      the American College of Chest Physicians and the American Association of
      Cardiovascular and Pulmonary Rehabilitation. The Global Initiative for Chronic
      Obstructive Lung Disease, which is also evidence-based, included the
      recommendation for referral to PR. Despite those recommendations, the
      availability of comprehensive PR programs (defined as being compliant with
      national practice standards) is limited. In the United States the lack of a
      national policy for PR reimbursement has led to differences in compensation among
      insurance providers, based on differences in the Local Medical Review Policies
      established by the "fiscal intermediaries." Since 1998 the American Association
      for Respiratory Care, the American College of Chest Physicians, the American
      Thoracic Society, and the National Association for Medical Direction of
      Respiratory Care have jointly lobbied for clear, consistent guidelines from the
      United States Health Care Financing Administration (HCFA, which was recently
      renamed the Centers for Medicare and Medicaid Services [CMS]). In 2002 new
      Medicare/Medicaid billing codes ("G codes") became available for billing PR
      procedures, but unfortunately the instructions for the use of those codes differ
      among the Local Medical Review Policies. There has been little success in the
      effort to establish a national coverage policy for PR. The respiratory therapist
      holds a unique role in PR. In the respiratory therapist's training curriculum PR
      is specifically addressed, making the respiratory therapist an asset to the
      multidisciplinary PR team. With their many clinical opportunities for making
      contact with COPD patients and physicians, respiratory therapists can be
      effective advocates for PR.

PMID- 14733619
TI  - Analysis of the lambdoid prophage element e14 in the E. coli K-12 genome.
AB  - BACKGROUND: Many sequenced bacterial genomes harbor phage-like elements or
      cryptic prophages. These elements have been implicated in pathogenesis, serotype
      conversion and phage immunity. The e14 element is a defective lambdoid prophage
      element present at 25 min in the E. coli K-12 genome. This prophage encodes
      important functional genes such as lit (T4 exclusion), mcrA (modified cytosine
      restriction activity) and pin (recombinase). RESULTS: Bioinformatic analysis of
      the e14 prophage sequence shows the modular nature of the e14 element which
      shares a large part of its sequence with the Shigella flexneri phage SfV. Based
      on this similarity, the regulatory region including the repressor and Cro
      proteins and their binding sites were identified. The protein product of b1149
      was found to be a fusion of a replication protein and a terminase. The genes
      b1143, b1151 and b1152 were identified as putative pseudogenes. A number of
      duplications of the stfE tail fibre gene of the e14 are seen in plasmid p15B. A
      protein based comparative approach using the COG database as a starting point
      helped detect lambdoid prophage like elements in a representative set of
      completely sequenced genomes. CONCLUSIONS: The e14 element was characterized for
      the function of its encoded genes, the regulatory regions, replication origin and
      homology with other phage and bacterial sequences. Comparative analysis at
      nucleotide and protein levels suggest that a number of important phage related
      functions are missing in the e14 genome including parts of the early left operon,
      early right operon and late operon. The loss of these genes is the result of at
      least three major deletions that have occurred on e14 since its integration. A
      comparative protein level approach using the COG database can be effectively used
      to detect defective lambdoid prophage like elements in bacterial genomes.

PMID- 14733621
TI  - Chronic obstructive pulmonary disease and sleep.
AB  - The control of breathing in patients with chronic obstructive pulmonary disease
      (COPD) follows the same basic principles as in normal subjects, both awake and
      asleep, with an expected lower feedback response during sleep. This impacts
      nocturnal gas exchange and sleep quality most profoundly in patients with more
      severe COPD, as multiple factors come into play. Hypoventilation causes the most
      important gas-exchange alteration in COPD patients, leading to hypercapnia and
      hypoxemia, especially during rapid-eye-movement sleep, when marked respiratory
      muscle atonia occurs. The hypoxia leads to increased arousals, sleep disruption,
      pulmonary hypertension, and higher mortality. The primary mechanisms for this
      include decreased ventilatory responsiveness to hypercapnia, reduced respiratory
      muscle output, and marked increases in upper airway resistance. In the presence
      of more profound daytime hypercapnia, polysomnography should be considered (over
      nocturnal pulse oximetry) to rule out other co-existing sleep-related breathing
      disorders such as obstructive sleep apnea (overlap syndrome) and obesity
      hypoventilation syndrome. Present consensus guidelines provide insight into the
      proper use of oxygen, continuous positive airway pressure, and nocturnal
      noninvasive positive-pressure ventilation for those conditions, but several
      issues remain contentious. In order to provide optimal therapy to patients, the
      clinician must take into account certain reimbursement and implementation-process
      obstacles and the guidelines for treatment and coverage criteria.

PMID- 14733622
TI  - Surgical therapies for chronic obstructive pulmonary disease.
AB  - Surgical procedures for treating emphysema were first developed nearly 100 years
      ago. Despite a wide range of surgical procedures performed over the years, only
      three appear to have true clinical benefit: bullectomy, lung volume reduction
      surgery (LVRS), and lung transplantation. Lung volume reduction surgery has been
      reintroduced in the past decade and is currently under active research. A recent
      large, multicenter trial showed LVRS to improve quality of life, exercise
      capacity, and even survival in certain highly selected patients. Some individuals
      with emphysema may be candidates for either LVRS or lung transplantation. Patient
      selection criteria for these procedures are being developed.

PMID- 14733623
TI  - Chronic obstructive pulmonary disease: emerging medical therapies.
AB  - As many as 10 million Americans have chronic obstructive pulmonary disease and as
      a consequence experience disabling symptoms, high cost of care, and substantial
      mortality. Several new approaches are being investigated for possible benefit in
      managing (or even reversing) chronic obstructive pulmonary disease. This article
      reviews 4 new approaches that are either in or close to phase III trials: long
      acting bronchodilators, phosphodiesterase-4 inhibitors, vasodilators, and
      retinoids. Of those tiotropium appears to be the closest to receiving clinical
      approval in the United States. The risk/benefit ratio and the cost-effectiveness
      of the other compounds are less clear and await additional study.

PMID- 14733624
TI  - Noninvasive ventilation for chronic obstructive pulmonary disease.
AB  - Noninvasive positive-pressure ventilation (NPPV) should be considered a standard
      of care to treat COPD exacerbations in selected patients, because NPPV markedly
      reduces the need for intubation and improves outcomes, including lowering
      complication and mortality rates and shortening hospital stay. Weaker evidence
      indicates that NPPV is beneficial for COPD patients suffering respiratory failure
      precipitated by superimposed pneumonia or postoperative complications, to allow
      earlier extubation, to avoid re-intubation in patients who fail extubation, or to
      assist do-not-intubate patients. NPPV patient-selection guidelines help to
      identify patients who need ventilatory assistance and exclude patients who are
      too ill to safely use NPPV. Predictors of success with NPPV for COPD
      exacerbations have been identified and include patient cooperativeness, ability
      to protect the airway, acuteness of illness not too severe, and a good initial
      response (within first 1-2 h of NPPV). In applying NPPV, the clinician must pay
      attention to patient comfort, mask fit and air leak, patient-ventilator
      synchrony, sternocleidomastoid muscle activity, vital signs, hours of NPPV use,
      problems with patient adaptation to NPPV (eg, nasal congestion, dryness, gastric
      insufflation, conjunctival irritation, inability to sleep), symptoms (eg,
      dyspnea, fatigue, morning headache, hypersomnolence), and gas exchange while
      awake and asleep. For severe stable COPD, preliminary evidence suggests that NPPV
      might improve daytime and nocturnal gas exchange, increase sleep duration,
      improve quality of life, and possibly reduce the need for hospitalization, but
      further study is needed. There is consensus, but without strong supportive
      evidence, that COPD patients who have substantial daytime hypercapnia and
      superimposed nocturnal hypoventilation are the most likely to benefit from NPPV.
      Adherence to NPPV is problematic among patients with severe stable COPD.

PMID- 14733625
TI  - Chronic obstructive pulmonary disease: the last year of life.
AB  - Nearly one quarter million Americans die with or of advanced chronic obstructive
      pulmonary disease (COPD) each year. Many patients die after a prolonged
      functional decline that is accompanied by much suffering. Though difficult
      prognostically and emotionally, anticipation of death opens the door to planning
      and preparing for terminal care. Epidemiologists have begun to identify
      characteristics of COPD patients who are most likely to die within 6-12 months,
      including severe, irreversible airflow obstruction, severely impaired and
      declining exercise capacity and performance status, older age, concomitant
      cardiovascular or other co-morbid disease, and a history of recent
      hospitalizations for acute care. Clinicians are encouraged to raise the difficult
      subject of planning for death when many of these characteristics apply. Patients
      with far-advanced disease are often receptive to the recommendation of a dual
      agenda: "Hope for and expect the best, and prepare for the worst." Medical
      advance planning is best pursued in an out-patient office during a prescheduled,
      3-way conversation between patient, health care proxy, and physician. An advance
      directive can be written after the meeting to summarize the conversation.
      Clinicians should consider recommending hospice care when a COPD patient is at
      high risk of respiratory failure from the next chest infection and in need of
      frequent or specialized home care. Preparation for death should include a
      realistic appraisal of the prospects for dying peacefully at home and a
      contingency plan for terminal hospitalization, should the need arise.

PMID- 14733626
TI  - Translating new understanding into better care for the patient with chronic
      obstructive pulmonary disease.
AB  - Despite an enormous amount of research and many official statements, the
      definition, diagnosis, and staging of chronic obstructive pulmonary disease
      (COPD) remain inconsistent, and we have yet to agree on who should be tested with
      spirometry or on where and how to do it. We know that inflammation, not just
      airflow limitation, is important in determining the course of COPD, especially
      with respect to exacerbations. We can detect and treat alpha-1 antitrypsin
      deficiency, an under-recognized condition, but whether alpha-1 antitrypsin
      augmentation therapy affects the disease's clinical course remains unclear.
      Smoking cessation is the most important of all interventions for COPD, with
      proven techniques and adjuncts, but implementation remains difficult and success
      rates are disappointingly low. Similarly, pulmonary rehabilitation has well
      documented benefits but is grossly underutilized because it is difficult to pay
      for and is not made available to most patients. Symptoms, costs, and other
      outcomes can be improved through comprehensive disease management, including the
      use of practice guidelines, yet multiple barriers prevent the potential benefits
      of these interventions to patients from being realized. Many patients who do not
      meet threshold oxygenation criteria for oxygen therapy during the daytime
      desaturate during sleep, but evidence that nocturnal oxygen administration
      benefits these patients is lacking. However, other sleep-related breathing
      disorders are common in COPD patients. Lung volume reduction surgery has recently
      been shown to improve function and survival for certain COPD patients, but lung
      transplantation has generally been disappointing. New pharmaceutical agents are
      being developed for treating COPD, and at least one of them (tiotropium) should
      soon be available in the United States. Noninvasive ventilation is effective in
      treating acute decompensations of COPD and should be the standard of care in that
      setting; evidence supporting its use in stable patients with end-stage disease is
      scant. Appropriate palliative care can greatly benefit patients and their
      families in the terminal phase of COPD and needs to be more widely applied.

PMID- 14733628
TI  - Clinical lung cancer - a promising start.

PMID- 14733627
TI  - Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder.
AB  - There is a substantial body of literature documenting the efficacy of multiple
      unrelated pharmacological agents in attention-deficit hyperactivity disorder
      (ADHD) individuals throughout the life-cycle. The available literature indicates
      the important role of psychopharmacological agents in the reduction of the core
      symptoms of ADHD and associated impairments. The literature documents that
      stimulants not only improve abnormal behaviours of ADHD, but also improves self
      esteem, cognition, and social and family function. However, response varied in
      different age groups and with certain comorbidities. In addition there is a large
      body of literature documenting the efficacy of atomoxetine which shows
      improvement in these same domains. More research is needed on alternative
      pharmacological treatments and to further evaluate established therapeutics
      beyond school-aged Caucasian boys. Further, more research is needed on the
      efficacy of treatment for comorbid ADHD, use of combined medications, and the
      combination of medication and psychosocial treatment.

PMID- 14733629
TI  - 10th European Cancer Conference (ECCO 10) Vienna, Austria and 17th Chemotherapy
      Foundation Symposium New York City, New York.

PMID- 14733630
TI  - Pathological examination and the reporting of lung cancer specimens.
AB  - The Lung Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice
      Guidelines Initiative first met in January of 1994. Included in the membership
      were three pathologists who, with the other members of the DSG, felt that a
      useful contribution to the work of the group would be a recommendation on
      standardized examination and reporting of lung cancer specimens. This review
      summarizes the consensus of the Lung Cancer DSG pathologists based on their
      review of the literature and proposes a standard synoptic report, the Primary
      Lung Cancer Check-Off Sheet. If generally adopted, this standard would improve
      the quality of reporting of clinical and pathological stage information. Such
      high-quality staging information is essential to define patient populations for
      clinical trials and for outcome analyses.

PMID- 14733631
TI  - Adjuvant therapy of non small-cell lung cancer.
AB  - Multiple randomized prospective trials have failed to show a definitive survival
      advantage for the administration of adjuvant therapy following complete resection
      of non small-cell lung cancer.

PMID- 14733632
TI  - Endoscopic laser ablation as palliative treatment of endobronchial,
      nonresectable, or recurrent lung cancer: assessment of its impact on quality of
      life.
AB  - Laser ablation (LA) is currently used in our institute as palliative treatment
      for endobronchial nonresectable or recurrent lung cancer. The objective of this
      study was to assess the impact of LA on the quality of life (QOL) in a large
      group of patients with endobronchial obstructions due to nonresectable or re
      current lung cancer. Evaluation was based on Eastern Cooperative Oncology Group
      performance status (ECOG PS) for the "objective" assessment of QOL and the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire-C30 version 1.0 (EORTC QLQ-C30(v1)) for the "subjective" assessment
      of QOL. From May 1994 to June 1997, 133 LAs were performed using neodymium:
      yttrium-aluminum garnet (Nd:YAG) laser at low power settings (< 30W) on 89
      evaluable patients (Male/Female 78/11, mean age 63.5/62.8 years, range 42-82/47
      73). The QOL was evaluated by ECOG PS and QLQ-C30(v1) at baseline (3 days before
      LA), t1 (7 days after LA), and t2 (1 month after LA). The objective tumor
      response was evaluated at t2. The objective tumor response to LA intervention was
      "excellent," ie, complete response (CR), in 33 (24.8%) patients and "fair," ie,
      partial response (PR), in 97 (72.9%) patients, with an overall response rate
      (ORR) of 97.7%. A highly significant decrease in high score (ECOG PS 3-4) was
      registered from baseline to t1 and from t1 to t2. However, at the same time a
      significant increase of low score (ECOG PS 0-2) was observed. The comparison of
      patient QOL assessment by QLQ-C30(v1) at different times during the study was
      also made; the functioning scales, the global QOL scale, and the symptom
      scales/items showed a highly significant improvement at t1 compared to baseline
      (P < 0.001), whereas only global QOL improved at t2 compared to t1. A comparison
      of baseline ECOG PS scale with QLQ-C30(v1) scale revealed a strong relationship
      between PS and the symptom "fatigue." Our study demonstrates that dramatic
      clinical improvement obtained by an effective though palliative treatment such as
      LA improves QOL based on both physician-rated (PS) and mostly self-rated (QLQ
      C30(v1)) assessment.

PMID- 14733634
TI  - Preoperative high-dose cisplatin versus moderate-dose cisplatin combined with
      ifosfamide and mitomycin in stage IIIA (N2) non small-cell lung cancer: results
      of a randomized multicenter trial.
AB  - Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2)
      non small-cell lung cancer (NSCLC). The majority of induction regimens employ
      cisplatin, although the importance of cis-platin dose in combination is unclear.
      A randomized trial was conducted to address whether higher pre-operative
      cisplatin doses result in improved survival and increased pathologic complete
      response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven
      N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP)
      (100 mg/m2) or moderate-dose cisplatin (MDCP) (50 mg/ m2) in combination with
      ifosfamide (3 g/m2) and mitomycin (6 mg/m2). Disease was restaged after 3 cycles,
      and those patients with response or stable disease underwent thoracotomy. From
      March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and
      37 received MDCP. Clinical characteristics were well matched. Radiographic
      response rate was 59% for HDCP patients and 30% for MDCP patients (P = 0.01).
      Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable
      disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP
      group (P = 0.5). Postoperative mortality was 11%. Pathologic complete response
      was observed in one patient who received MDCP. Median survival in the HDCP and
      MDCP groups was 13 and 11 months, respectively (P = 0.3). In conclusion, higher
      radiographic response rate is observed in patients who receive HDCP, but this
      study fails to show any significant improvement in either overall survival or
      pathologic complete response in this group of patients.

PMID- 14733635
TI  - Cancer vaccines for the treatment and prevention of non small-cell lung cancer.
AB  - Cancer vaccines targeting non small-cell lung cancer (NSCLC) have been studied
      for decades; clinical trials, for the most part, have focused on the use of
      autologous and allogeneic whole-tumor cell vaccines. Recent advances in molecular
      biology and immunology, however, have allowed the identification of many tumor
      antigens involved in the generation of immunity to NSCLC. Although small-cell
      lung cancer (SCLC) is commonly thought of as an immunogenic tumor, it is now
      clear that NSCLC is also capable of eliciting an endogenous immune response in
      patients with the disease and, in fact, has a natural history that may make NSCLC
      more amenable to vaccine therapy as an adjuvant treatment strategy. This review
      will high-light the major components of the immune system that may potentially
      interact with tumor-associated proteins as well as outline the immunologic
      similarities and differences between SCLC and NSCLC. Tumor antigens that elicit
      immune responses in patients with NSCLC will be discussed. Finally, clinical
      trials of whole-tumor cell vaccines, both autologous and allogeneic, and tumor
      antigen-specific vaccines will also be discussed.

PMID- 14733636
TI  - Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) gene therapy
      protection of the esophagus from chemoradiotherapy damage during treatment of
      locally unresectable non-small-cell lung cancer (NSCLC).

PMID- 14733637
TI  - A phase I trial of outpatient weekly irinotecan/carboplatin and concurrent
      radiation for stage III unresectable non small-cell lung cancer: a Vanderbilt
      Ingram Cancer Center Affiliate Network Trial.
AB  - Irinotecan (CPT-11), a topoisomerase I inhibitor, has been shown in preclinical
      studies to be a potent radiosensitizer. Carboplatin, a known radiosensitizer with
      single-agent activity in non small-cell lung cancer (NSCLC), is felt to be a
      rational choice in combination with irinotecan. We have completed the initial
      portion of a phase I study, in patients with locally unresectable lung cancer,
      combining irinotecan with thoracic radiation. Thirteen patients have been entered
      onto this study through three dose levels (30 to 50 mg/m2/week) of irinotecan.
      There were seven partial responses in 12 evaluable patients, for an over-all
      response rate of 58%. Nausea, vomiting, and esophagitis were the principal
      toxicities of weekly irinotecan and concurrent thoracic radiation. As the maximum
      tolerated dose (MTD) of irinotecan with radiation has been established at 40
      mg/m2/week, we are currently accruing patients to the second phase of this study
      with the addition of carboplatin (AUC = 2). Thus far toxicity has primarily been
      esophagitis.

PMID- 14733638
TI  - Lung cancer in the new millennium.

PMID- 14733639
TI  - Paclitaxel/etoposide/cisplatin versus etoposide/cisplatin for small-cell lung
      cancer.

PMID- 14733640
TI  - Paclitaxel 175 mg/m2 plus carboplatin versus paclitaxel 225 mg/m2 plus
      carboplatin for advanced non small-cell lung cancer (NSCLC).

PMID- 14733641
TI  - Small-cell lung cancer at the millennium: radiotherapy innovations improve
      survival while new chemotherapy treatments remain unproven.
AB  - Because of the systemic nature of small-cell lung cancer, one could predict that
      treatment advances would mainly come from innovations of chemotherapy. Although
      combination chemotherapy is better than monotherapy, a clearly superior multidrug
      regimen has not emerged. Investigations of more intensive chemotherapy with
      increased drug diversity and delivery have not prospered, and advantages of
      regimens including new agents have not yet been demonstrated in controlled
      trials. As we enter the new millennium, twenty-five years have passed since the
      publication of studies describing the combined used of cyclophosphamide,
      doxorubicin, and vincristine for small-cell lung cancer. It has been almost 20
      years since the publication of the combination of etoposide and cisplatin became
      the widely accepted standard for the treatment of small-cell lung cancer. Today,
      both treatment regimens continue to be widely used as standard therapy.
      Ironically, proven advances in this systemic disease have been associated with
      innovations of local therapy. Data from limited-stage small-cell lung cancer
      clinical trials published during the 1990s demonstrated that a number of
      radiotherapy interventions had significant survival benefits. These radiotherapy
      interventions include addition of thoracic irradiation to chemotherapy, early
      delivery of thoracic irradiation concurrently with chemotherapy, more intense
      thoracic irradiation, and prophylactic cranial irradiation. As we await improved
      systemic therapy in the next millennium, the prognosis for extensive-stage
      disease remains guarded, and adherence to optimal radiotherapy detail remains
      crucial for routine management of limited-stage patients.

PMID- 14733643
TI  - Multimodality treatment of resectable non small-cell lung cancer.
AB  - In early-stage, resectable non small-cell lung cancer other than stage IA,
      survival following surgical resection has been disappointing. Many phase III
      adjuvant trials using postoperative chemotherapy, radiotherapy, or chemoradiation
      have had disappointing results results that have been confirmed by two recent
      meta-analyses. Preoperative radiotherapy combined with surgery has also failed to
      improve survival following surgical resection. For the past 20 years, several
      phase II trials have investigated the use of induction therapies (chemotherapy or
      chemoradiation) prior to surgery in the management of stage IIIA lung cancer. The
      phase II trials have been encouraging, and two small phase III trials have
      confirmed the efficacy of the multimodality approach. Newer, more tolerable
      chemotherapeutic agents are now being investigated. Because of the encouraging
      results in locally advanced disease, this induction therapy has been used in two
      trials of early stage (IB, II) disease; both trials have suggested that induction
      therapy improved patient tolerance to chemotherapy and in one trial perhaps
      improved survival. Currently, several phase III trials are attempting to confirm
      these early encouraging reports.

PMID- 14733645
TI  - Interim analysis of a phase III trial comparing cisplatin, gemcitabine, and
      vinorelbine vs. either cisplatin and gemcitabine or cisplatin and vinorelbine in
      advanced non small-cell lung cancer. A Southern Italy Cooperative Oncology Group
      Study.
AB  - In a previous phase II randomized study, a cisplatin/gemcitabine/vinorelbine
      (PGV) regimen produced a 50-week median survival time (MST) in advanced non small
      cell lung cancer (NSCLC) patients. The present trial was planned to randomly
      compare the outcome of patients treated with this new triplet regimen with those
      of patients receiving either cisplatin plus vinorelbine (PV) or cisplatin plus
      gemcitabine (PG) doublet combinations. One hundred eighty patients with stage
      IIIB (76) or IV (104) disease, aged <or= 70 years, and with Eastern Cooperative
      Oncology Group performance status (ECOG PS) <or= 1, were randomly allocated to
      receive: cisplatin, 50 mg/m2 plus gemcitabine, 1000 mg/m2 plus vinorelbine, 25
      mg/m2 (PGV) on days 1 and 8 every 3 weeks; cisplatin, 100 mg/m2 on day 1 plus
      gemcitabine, 1000 mg/m2 (PG) on days 1, 8, and 15 every 4 weeks; cisplatin, 120
      mg/m2 on days 1 and 29 plus vinorelbine, 30 mg/m2/week (PV). At the planned
      interim analysis, the MST of patients in the PGV, PG, and PV arms was 51, 42, and
      35 weeks, respectively. The hazard of death (Cox analysis) for patients receiving
      PGV compared with those receiving PV was 0.35 (95% confidence index [CI], 0.16
      0.77, P = 0.0058). The response rate was 47% in the PGV arm, 30% in the PG arm,
      and 25% in the PV arm. Severe neutropenia (75% vs. 45%), and vomiting (50% vs.
      15%) significantly affected more patients in the PV than in the PGV arm. Since
      the difference in survival met early stopping rules, accrual to the PV arm was
      suspended. Enrollment still continues in the PGV and PG arms to ascertain whether
      the triplet regimen has a more significant effect on survival than that produced
      with the PG regimen.

PMID- 14733647
TI  - Clinical characteristics and the impact of surgery and chemotherapy on survival
      of patients with advanced and metastatic bronchioloalveolar carcinoma: a
      retrospective study.
AB  - We retrospectively analyzed data from the clinical charts of 126 patients with
      bronchioloalveolar carcinoma (BAC) referred to the Ottawa Regional Cancer Center.
      The patient group consisted of 49 men (39%) and 77 women (61%). The mean age at
      diagnosis was 64 years. Most patients were smokers (85%). At diagnosis, 53% were
      stage Ia-IIIa and 47% were stage IIIb and IV. Forty-one percent of the patients
      with advanced and metastatic stages (IIIb, IV) underwent surgery. Multifocal
      disease was present at diagnosis in 41% of the patients, including 6% who had
      stage IIIb multifocal disease confined to a single lobe. Surgery was associated
      with prolonged survival in patients with multifocal unilobar or multilobar
      disease (P = 0.0001). While this apparent benefit of surgery may have been due to
      selection bias, it supports further exploration of surgery as therapy for
      multifocal disease. While patients receiving chemotherapy for advanced disease
      did not survive longer than patients not receiving chemotherapy, chemotherapy was
      used primarily in patients with more aggressive disease, suggesting that
      selection bias may have contributed to its apparent lack of benefit. Of the 30
      patients treated with chemotherapy, only 3 (10%) achieved an objective response.
      One third of the patients (34%) developed distant metastases, with a predilection
      for the brain and bone.

PMID- 14733649
TI  - Gene therapy for lung cancer.
AB  - Gene therapy is emerging as a promising modality for the treatment of lung
      cancer. Diverse strategies employing gene therapy for lung cancer have been
      investigated in vitro and in animal models, and a number of these approaches have
      met with promising results. Several phase I and II clinical trials have been
      undertaken, and early results suggest that it may be safe to administer gene
      therapy to lung cancer patients. It remains to be determined whether this
      modality will be efficacious as primary or adjunctive therapy in the setting of
      lung cancer.

PMID- 14733650
TI  - Phase I study of recombinant carcinoembryonic antigen (CEA) vaccinia virus
      vaccine with post vaccination carcinoembryonic antigen peptide (CAP-1) boost.

PMID- 14733651
TI  - Anatomic lung resections using minimally invasive thoracic surgery (MITS).
AB  - We have designed a minimally invasive thoracic surgery (MITS), which, in this
      report, we compare to the conventional muscle-sparing thoracotomy (MST). We
      retrospectively compared 70 consecutive MITS patients (mean age, 65 years) and 70
      consecutive MST patients (mean age, 60 years) who underwent thoracotomies for
      similar pathologies between 1995 and 1997. All comparisons between the MITS and
      MST groups were made using the Student's t-test. Extubation times, intensive care
      unit (ICU) stays, analgesia requirements, morbidities/mortalities, hospital
      lengths of stay (LOS), and cost analyses were all compared. Nine of the 70
      planned MITS procedures were converted intraoperatively to MST. All nine of these
      patients were admitted to the ICU. All of the MST patients spent a minimum of 24
      hours in the ICU. The mean LOS in the MITS group was 2.87 days with a mean
      hospital cost of 6,480.00 dollars, while in the MST group it was 8.28 days (P =
      0.003) and 11,490.00 dollars (P = 0.006). There were no deaths and 6
      complications in the MITS series. There were two mortalities and 15 complications
      in the MST patients. Our MITS procedure not only may be performed with low
      morbidity and cost, it also allows early ambulation and early hospital discharge.

PMID- 14733655
TI  - Lung cancer screening in high-risk populations.
AB  - Although the number of smokers per capita has declined appreciably in the United
      States in the past 30 years, smokers still make up about one quarter of the adult
      population. It does not appear that the number of US smokers will decrease
      further in the next century, and the number may even increase due to the
      popularity of smoking among teenagers. Epidemiological data indicate that women
      are more susceptible, dose-for-dose, to the adverse effects of tobacco smoke.
      Since women make up a large percentage of today s smokers, lung cancer rates may
      increase in the future. Current guidelines recommend against lung cancer
      screening based on chest x-ray and sputum morphology; however, new highly
      sensitive detection methods are available that may make screening more effective,
      especially if combined with analysis of risk factors for lung cancer and
      biomarkers of damage to the airways that may identify individuals at highest risk
      for lung malignancies. Lung cancer will continue to be a major public health
      problem in the next century. Advances in the field of early detection may make
      lung cancer screening practical and effective in the near future.

PMID- 14733657
TI  - The benefits of support group participation to lung cancer survivors--an
      evaluation.
AB  - It has been known for some time that participation in support groups is
      beneficial for most cancer survivors. Despite this, and even though lung cancer
      causes more deaths than breast, prostate, and colorectal cancers combined, the
      number of support groups formed for lung cancer survivors is surprisingly very
      small. In an effort to understand the lack of lung cancer specific support
      groups, the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE)
      conducted a survey of the facilitators of the lung cancer support groups then
      known to be in existence in the United States, in addition to a follow-up focus
      group with the facilitators via teleconference. The results of the survey and the
      focus group provide a very preliminary look at the value to lung cancer survivors
      of participating in support groups organized specifically for them. However, much
      more research is required, not only with the participants of these groups, but
      also with lung cancer survivors who do not participate, to fully gauge the
      effects of support group participation on the progress of their disease and on
      their quality of life.

PMID- 14733660
TI  - Sequential chemotherapy: rationale and clinical trial design in advanced non
      small-cell carcinoma.
AB  - Recent developments in the chemotherapy of advanced and metastatic non small-cell
      lung cancer have led to significant, albeit modest, improvements in survival and
      quality of life. The plethora of new agents with activity in this disease has led
      to questions as to how these drugs can best be added to existing regimens.
      Traditionally, the paradigm of combination chemotherapy has dominated this
      approach with new agents added to older regimens. Unfortunately, this will
      frequently lead to additive toxicity and necessitate reduction in the doses of
      individual components of the combination. The planned sequential administration
      of new chemotherapy agents circumvents this problem. Additionally, considerable
      theoretical, biological, and clinical evidence supports this approach. This paper
      reviews the rationale for this strategy and discusses initial data from a pilot
      trial of this approach.

PMID- 14733663
TI  - Lung cancer: value of various imaging modalities.
AB  - Bronchogenic carcinoma is the leading cause of cancer death, and the overall
      prognosis remains poor. Imaging plays a critical role in the initial staging and
      follow-up of the disease. Bronchogenic carcinoma is typically detected first on
      chest radiography but computed tomography (CT) scan is the most important imaging
      technique, providing both staging information and assessment of recurrence.
      Magnetic resonance imaging (MRI) is most useful as a problem-solving tool. The
      increasing role of positron emission tomography (PET) scan in the evaluation is
      reviewed, and imaging guidelines of two national organizations are presented.

PMID- 14733665
TI  - The anti-apoptosis survivin gene and its role in human cancer: an overview.
AB  - Malignant transformation of cells is accompanied by multiple genetic
      abnormalities with aberrant expression of genes. By using the reverse
      transcriptase polymerase chain reaction (RT-PCR) assay, we have assessed the
      regulation of survivin gene expression in a prospectively collected series of 83
      human non small-cell lung cancers. Survivin gene transcripts were identified in
      71 (85.5%) of the tumor samples, while they were detected in only 10 (12%) of the
      paired histopathologically normal lung samples. Furthermore, a diminished overall
      survival was associated with survivin expression (Log-rank, P=0.01). This review
      discusses the structure, expression, and function of the survivin gene. It
      presents updated pooled data on survivin, analyzed by either immunochemistry or
      by RT-PCR, and the clinical correlates of aberrant expression in several tumors.
      We conclude that estimation of survivin gene transcripts by RNA techniques may
      have relevant applications in the prognostic and therapeutic assessment of lung
      cancer.

PMID- 14733666
TI  - Docetaxel and cisplatin in patients with advanced non small-cell lung cancer
      (NSCLC): a multicenter phase II trial.
AB  - We examined the safety and efficacy of the docetaxel/cisplatin combination in
      patients with advanced, previously untreated NSCLC and evaluated changes in
      quality of life over time. Docetaxel was administered before cisplatin (both 75
      mg/m2, 1-hour infusions) every 3 weeks to 47 patients with stage IIIB or stage IV
      NSCLC. Patients also received premedication of oral dexamethasone. The median age
      (range) of patients was 62 (45-78) years and 26 patients (55.3%) had
      adenocarcinoma. Of the 40 patients evaluable for response, one achieved a
      complete response and 14 had partial responses; the response rate was 37.5% (95%
      confidence intervals; 22.5, 52.5). In the intent-to-treat population the overall
      response rate was 31.9%. Time to response ranged from 3 to 20 weeks, and the
      median duration of response was 34.6 weeks. Median survival and median time to
      progression were 11.3 months and 18.9 weeks, respectively. One-year survival was
      40%. Grade 3 or 4 neutropenia and febrile neutropenia were observed in 74.4% and
      12.8% of patients, respectively. Severe asthenia was seen in 14.9% of patients.
      Other grade 3 or 4 toxicities included nausea (eight patients), vomiting (five),
      neurosensory effects (six), neuromotor effects (five), diarrhea (four), and
      infection (three). There was an improvement in emotional well-being; however, the
      overall quality of life score did not change with treatment. Docetaxel
      administered in combination with cisplatin is an active regimen in patients with
      NSCLC. This regimen of docetaxel (75 mg/m2) and cisplatin (75 mg/m2) repeated at
      3-week intervals is being evaluated in an ongoing Eastern Cooperative Oncology
      Group (ECOG) randomized study in patients with advanced and metastatic NSCLC.

PMID- 14733667
TI  - Phase I study of bryostatin-1 in combination with cisplatin in treating patients
      with metastatic or unresectable solid tumors including non small-cell lung
      cancer.

PMID- 14733668
TI  - Twice-weekly gemcitabine and concurrent thoracic radiation for advanced non small
      cell lung cancer.

PMID- 14733669
TI  - Pre-West Nile virus outbreak: perceptions and practices to prevent mosquito bites
      and viral encephalitis in the United States.
AB  - Mosquitoes can transmit over 100 of the viruses that can cause encephalitis,
      meningitis, and hemorrhagic disease in humans (Chin 2000; Gubler 1996; Monath
      1989). While much is known about the ecology, epidemiology, and clinical
      manifestations of the arboviral encephalitides (Campbell et al. 2002; Centers for
      Disease Control and Prevention 1997; Gubler 1998; Hayes 1989; Hubalek and
      Halouzka 1999), little empirical research exists regarding the U.S. population's
      knowledge of mosquitoes and arboviral encephalitis, particularly prior to the
      U.S. outbreak of West Nile virus (WNV) in 1999. A nationally representative 55
      item survey instrument was successfully administered to 1,500 adults in the
      United States and an additional 250 adults in six states in the Northeast
      (Connecticut, Delaware, New Jersey, New York, Pennsylvania, and Rhode Island)
      regarding mosquitoes and mosquito-borne viral encephalitis. A summary outcome
      measure for mosquito bite prevention was created. Analyses revealed that the
      following were statistically significant predictors of behaviors taken to prevent
      mosquito bites: being concerned about being bitten by mosquitoes, perceived
      effectiveness of staying indoors in late afternoon and early evening was
      protective, perceived effectiveness that mosquito repellent is not harmful to
      health, owning dogs and/or cats as pets, being married, and being > or = 18-44
      years old. Being concerned about being bitten by mosquitoes was the most robust
      predictor of behavioral action to prevent mosquito bites (OR = 7.3; 95% CI = 4.3,
      12.2). Observed misperceptions and inadequate knowledge regarding insect
      repellents suggest increased promotion of the safety and efficacy of DEET
      containing insect repellents is warranted.

PMID- 14733670
TI  - Cationic antimicrobial peptide killing of African trypanosomes and Sodalis
      glossinidius, a bacterial symbiont of the insect vector of sleeping sickness.
AB  - Nine biochemically distinct cationic antimicrobial peptides were tested in vitro
      for their effects on bloodstream forms and procyclic (insect) forms of African
      trypanosomes, the protozoan parasites that cause African sleeping sickness in
      humans and trypanosomiasis in domestic animals. At low concentrations, one
      peptide completely inhibited growth of bloodstream forms, one inhibited procyclic
      forms, and five inhibited both trypanosome life cycle stages. The peptides were
      also tested on Sodalis glossinidius, a bacterial symbiont of tsetse flies. S.
      glossinidius was highly resistant to seven of the nine peptides, including both
      that specifically inhibited either bloodstream or procyclic forms and three of
      the five that inhibited both trypanosome life cycle stages. The results indicate
      that several of these peptides may be ideal candidates for therapy of trypanosome
      infected mammals or for transgenic expression in S. glossinidius as a strategy
      for inhibiting trypanosome survival, development, and maturation in tsetse and
      interference with transmission of African sleeping sickness.

PMID- 14733671
TI  - A serosurvey of leptospirosis in Connecticut peridomestic wildlife.
AB  - Recently, leptospirosis has gained attention as a re-emerging infection in
      domestic dogs in the northeastern United States. In order to gain insight into
      the epizootiology of leptospirosis in this region, 109 small wild mammals (31
      raccoons (Procyon lotor), 30 skunks (Mephitis mephitis), 28 opossums (Didelphis
      virginiana), and 20 gray squirrels (Sciurus carolinensis)) collected between
      February 27 and September 17, 2001 were tested for serologic evidence of exposure
      to five common Leptospira serovars (serovars pomona, icterohemorrhagiae,
      canicola, hardjo, grippotyphosa). Evidence of exposure to leptospirosis was
      detected in 36% of raccoons tested; icterohemorrhagiae was the predominant
      reactive serovar in these animals. Sera from 13% of skunks showed evidence of
      exposure to serovar grippotyphosa. One squirrel exhibited high antibody titers to
      serovars grippotyphosa and canicola. All 28 opossums examined tested negative to
      the five Leptospira serovars. Results from this serosurvey suggest that common
      peridomestic wildlife species should be considered as potential sources of
      leptospirosis to dogs and humans in Connecticut. Additional investigation is
      warranted to clarify their role in the epidemiology of this zoonotic disease in
      the northeastern United States.

PMID- 14733673
TI  - Serologic evidence of West Nile Virus infection in birds, Tamaulipas State,
      Mexico.
AB  - Following the introduction of West Nile virus (WNV) into North America in 1999,
      surveillance for WNV in migratory and resident birds was established in
      Tamaulipas State, northern Mexico in December 2001. Overall, 796 birds
      representing 70 species and 10 orders were captured and assayed for antibodies to
      WNV. Nine birds had flavivirus-specific antibodies by epitope-blocking enzyme
      linked immunosorbent assay; four were confirmed to have antibody to WNV by plaque
      reduction neutralization test. The WNV-infected birds were a house wren, mourning
      dove, verdin and Bewick's wren. The house wren is a migratory species; the other
      WNV-infected birds are presumably residents. The WNV-infected birds were all
      captured in March 2003. These data provide the first indirect evidence of WNV
      transmission among birds in northern Mexico.

PMID- 14733672
TI  - Evaluation of a prototype Ehrlichia chaffeensis surveillance system using white
      tailed deer (Odocoileus virginianus) as natural sentinels.
AB  - The natural history of Ehrlichia chaffeensis, the causative agent of human
      monocytotropic ehrlichiosis, includes the lone star tick (LST, Amblyomma
      americanum) as a vector and white-tailed deer (WTD; Odocoileus virginianus) as
      both a natural reservoir of E. chaffeensis and a major host of LST. The goal of
      the current study was to implement and evaluate a prototype surveillance system
      to delineate the geographic distribution of E. chaffeensis using WTD as natural
      sentinels. To accomplish this goal, serologic testing using the indirect
      immunofluorescent antibody (IFA) test was performed on WTD serum samples, and to
      confirm serologic results, polymerase chain reaction (PCR) assays and culture
      isolation were conducted. Considerations relevant to the applicability of a
      surveillance system utilizing WTD were analyzed (e.g., age and gender
      relationships to serologic status, adequacy of sample sizes needed to distinguish
      between uninfected and infected populations, presence of LST, and ability to
      detect stability and spread of E. chaffeensis in WTD populations). Of 3275 WTD
      serologically tested, 549 (47%) from 17 of 18 states had antibodies reactive to
      E. chaffeensis (IFA titer > or = 1:128). No difference between age groups or
      gender was noted with serologic testing, thus these variables would not be a
      concern for a surveillance system using WTD. Significantly more deer in younger
      age groups (< or = 1.5 yr) were PCR and culture positive, and 46% of 122
      seropositive WTD populations were confirmed positive by PCR or culture isolation.
      A significant association between LST infestation and E. chaffeensis
      seroreactivity was noted. Furthermore, the surveillance system was able to detect
      stability of E. chaffeensis within WTD populations and also spread to new
      populations, both of which were associated with LST status. These data clearly
      demonstrate that WTD are useful as natural sentinels for this emerging human
      pathogen, and establish a prototypical framework for a WTD surveillance system.

PMID- 14733674
TI  - Diagnosis of lyme borreliosis in europe.
AB  - In Europe, Lyme borreliosis is caused by at least three species, B. burgdorferi
      sensu stricto, B. afzelii and B. garinii. Thus microbiological diagnosis in
      European patients must consider the heterogeneity of Lyme disease borreliae for
      development of diagnostic tools such as PCR primers and diagnostic antigens.
      According to guidelines of the German Society of Hygiene and Microbiology, the
      serological diagnosis should follow the principle of a two-step procedure. A
      sensitive ELISA differentiating IgM and IgG is recommended as the first step. In
      case the ELISA is reactive, it is followed by immunoblots (IgM and IgG) as the
      second step. The reactive diagnostic bands should be clearly identified, which is
      easy if recombinant antigens are used. The sensitivity and standardization of
      immunoblots has been considerably enhanced by use of recombinant antigens instead
      of whole cell lysates. Improved sensitivity resulted from use of recombinant
      proteins that are expressed primarily in vivo (e.g., VlsE) and combination of
      homologous proteins from different strains of borrelia (e.g., DbpA). It also
      appears promising to use recombinant proteins (DbpA, VlsE, others) or synthetic
      peptides (the conserved C6 peptide derived from VlsE) as ELISA antigens. At
      present, detection rates for serum antibodies are 20-50% in stage I, 70-90% in
      stage II, and nearly 100% in stage III Lyme disease. The main goals for the
      future are to improve specificity in general and sensitivity for diagnosis of
      early manifestations (stage I and II). Detection of the etiological agent by
      culture or PCR should be confined to specific indications and specialised
      laboratories. Recommended specimens are skin biopsy specimens, CSF and synovial
      fluid. The best results are obtained from skin biopsies with culture or PCR (50
      70%) and synovial tissue or fluid (50-70% with PCR). CSF yields positive results
      in only 10-30% of patients. Methods that are not recommended for diagnostic
      purposes are antigen tests in body fluids, PCR of urine, and lymphocyte
      transformation tests.

PMID- 14733675
TI  - Reflections on the clinical and epidemiological studies presented at the IX
      International Conference on Lyme Borreliosis and Other Tick-Borne Diseases and
      future directions.

PMID- 14733676
TI  - An interview with Patricia Nuttall, Ph.D. Interview by Vicki Glaser.

PMID- 14733678
TI  - Interns learning to care for dying patients.
AB  - OBJECTIVE: To examine interns' perceptions of the emotional support they were
      able to provide to dying patients and their families, as well as their evaluation
      of attending physicians as role models caring for dying patients and their
      families. METHODS: A semistructured, face-to-face interview of a convenience
      sample of 38 internal medicine interns in two New York City teaching hospitals
      who were the primary house officers of patients dying between January 2000 and
      April 2000. RESULTS: Fifty-eight percent of interns rated their comfort level in
      talking to their patient and family about end-of-life issues as good to
      excellent. Sixty percent of interns estimated that their impact on their
      patient's emotional experiences as they approached death as none to minimal.
      Seventy-four percent of interns rated their patient's physical comfort level good
      to excellent. Interns rated attending physicians as effective role models in 66%
      of cases; 34% percent were rated as poor to mediocre. Observation of attending
      physicians with patients and families was rated as the most effective method to
      learn how to care for dying patients. CONCLUSIONS: While most interns felt
      comfortable speaking to their patients and their families about end-of-life
      issues, they also believed that they provided only minimal emotional support.
      Interns believe that direct observation of attending physicians is the most
      effective way to improve their skills caring for dying patients and their
      families; however, they report wide variability in attending physician
      performance as role models.

PMID- 14733679
TI  - The pursuit of physician-assisted suicide: role of psychiatric factors.
AB  - Physician-assisted suicide (PAS) has attracted considerable professional
      attention in recent years in the end-of-life care debate. The role of depression
      and other psychiatric illnesses on the patient's pursuit of PAS is unclear. As
      part of a qualitative study exploring the motivations, deliberations, and
      complications experienced by persons with incurable diseases who were actively
      seeking PAS, we conducted semistructured interviews that were reviewed for
      psychiatric content. In total, 159 interviews were conducted with 60 participants
      concerning 12 prospective cases (12 patients and 20 family members) and 23
      retrospective cases (28 family members), with more than 3600 pages of
      transcripts. Depressive symptoms, when present, were not described by the
      subjects and/or their family members to be an influential factor in their pursuit
      of PAS; no subject appeared or was described to suffer from depression-related
      decisional incapacity. Findings from this study, albeit from a small and self
      selected sample, highlight not only the importance of avoiding a reductionistic
      understanding of the role of psychiatric illnesses in contributing to serious
      pursuit of PAS, but also the pressing need for scientifically rigorous studies of
      PAS in samples representative of the larger population.

PMID- 14733680
TI  - Barriers to limiting the practice of feeding tube placement in advanced dementia.
AB  - OBJECTIVE: In advanced dementia, many difficult decisions may arise as the
      disease progresses, including whether to use feeding by tube. Several recent
      articles question the benefit of percutaneous endoscopic gastrostomy (PEG) tube
      placement in persons with advanced dementia. However, patients with advanced
      dementia are still referred for PEG tubes. This study attempts to understand more
      about physician decisions to recommend PEG tube placement in patients with
      advanced dementia. DESIGN: Mailed survey. SETTING: Random sample of 500
      physicians from the American Medical Association Masterfile. PARTICIPANTS:
      Primary care physicians. MEASUREMENTS: Physician knowledge, beliefs, and self
      reported practices of PEG tubes in advanced dementia. RESULTS: Of the 416
      eligible participants, 195 completed surveys (response rate of 46.9%). A
      significant number of physicians believe PEG tubes have the following benefits in
      advanced dementia: reduce aspiration pneumonia (76.4%), and improve pressure
      ulcer healing (74.6%), survival (61.4%), nutritional status (93.7%), and
      functional status (27.1%). Most physicians underestimate 30-day mortality in
      patients who receive a PEG and more than half of physicians believe PEG tubes in
      advanced dementia are the standard of care. Also, a majority of physicians
      believe speech therapists, nurses, and nutritional support teams recommend
      feeding tubes, which influences their decision to recommend a PEG. Last, almost
      half of these respondents had a nursing home request PEG tube placement, leading
      physicians to recommend a PEG. CONCLUSIONS: We find a notable discord between
      physician opinion, reported practice, and the literature regarding PEG tubes in
      advanced dementia that reveals some of the barriers to decreasing the referral of
      these patients for PEG.

PMID- 14733681
TI  - The last forty-eight hours of life in a Portuguese palliative care unit: does it
      differ from elsewhere?
AB  - The last few days of life have received significant attention in the literature.
      Reports have shown similarities and differences between programs. As a palliative
      care service in a cultural context that has not been reported on, we thought that
      an audit of our own experience in the care of patients in the last 48 hours of
      life and a comparison with other programs would be important. A prospective audit
      was designed to record data for four general domains: general demographic
      information, symptom prevalence, patient performance status, and perceived level
      of comfort. The inclusion criteria of patients were: older than 15 years of age
      (an admission criterion for patients of the unit), diagnosis of cancer, no active
      cancer-direct treatments, and patients who were on the unit for longer than 48
      hours. The audit was completed when the 300th eligible patient died in the unit.
      Twenty-nine of 300 patients (9.6%) required sedation and the most common cause
      was delirium. Morphine was the most widely prescribed medication (85% of
      patients). The subcutaneous route was utilized extensively. Only 12% of the
      patients received parenteral fluids, usually via hypodermoclisis. Death was
      considered by staff to have been peaceful in 86% of cases. Our practice appears
      to mirror that of other palliative care groups.

PMID- 14733682
TI  - End-of-life caregiving: what helps family caregivers cope?
AB  - Patient care needs and patient quality-of-life (QOL) deficits can be significant
      stressors for family caregivers. Often, greater caregiving demands and poorer
      patient QOL are associated with greater caregiver strain. However, caregiver
      coping behavior can attenuate the effect of caregiving stressors on caregiver
      strain. This study examined the relationships among caregiving stressors, coping,
      and caregiver strain in a sample of 31 family caregivers and their terminally ill
      loved ones enrolled in home hospice programs. Caregiving stressors included
      patient activity of daily living (ADL) needs and dimensions of patient QOL.
      Coping was measured with the Family Crisis Personal Evaluation Scale (F-COPES),
      which has five coping scales: acquiring social support, reframing, seeking
      spiritual support, passive appraisal, and mobilizing the family to acquire and
      accept help. Caregiver strain was significantly correlated with patient ADL needs
      (r = 0.51), patient psychological distress (r = 0.42), and patient existential
      QOL (r = -0.65). Regression equations indicated that reframing coping lessened
      caregiver strain. Caregivers who accepted their loved one's illness, redefined
      illness-related problems in a more manageable way, and felt capable of solving
      illness-related problems had less caregiver strain than caregivers who used less
      of a reframing coping style.

PMID- 14733684
TI  - Social work and spiritual counseling: results of one state audit.
AB  - Interdisciplinary care is the foundation of hospice service for the terminally
      ill. This model of care includes a holistic focus on the patient and family,
      including not only physical and medical management but also psychological and
      spiritual needs. The importance of social issues is acknowledged and supported
      through federal and state regulations requiring social work and spiritual
      counseling services as a part of the hospice care team. State regulatory reports
      were analyzed to identify compliance issues for social workers and spiritual
      counselors within hospice programs in a midwestern state. Problems with care
      planning, assessment, and bereavement services were identified in this process.
      Deficiencies point to the opportunities for social work educators to improve the
      training of future hospice social workers and the challenges involved in training
      spiritual counselors.

PMID- 14733683
TI  - Primary care continuity and location of death for those with cancer.
AB  - BACKGROUND: Continuity of primary care is known to be associated with both
      improved processes and outcomes of care. Despite continuity being a desired
      attribute of end-of-life care and despite the desire by most patients with cancer
      to die at home, there has been no health services research examining this
      relationship. AIM: To examine the association between family physician continuity
      of care and the location of death for patients with cancer. DESIGN OF STUDY: A
      retrospective population-based study involving secondary data analysis of four
      linked administrative health databases spanning 6 years of information (1992
      1997). SETTING: Nova Scotia, Canada Participants: All those who died of cancer
      from 1992 to 1997 and had made at least three ambulatory visits to a family
      physician. METHODS: The relationship of provider continuity of care and an out-of
      hospital death was examined using logistic regression. RESULTS: Out-of-hospital
      deaths accounted for 31.6% of the 9714 deaths in the study population. The mean
      provider continuity of care was 0.78 (standard deviation [SD] 0.22). Those who
      died out-of-hospital had a greater odds of having received high provider
      continuity (adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.22,
      1.93) when compared to those who died in-hospital. There appears to be a
      modification of this effect by gender with a significant association found for
      males and not for females. The trends in the point estimates are, however,
      similar for both sexes. CONCLUSIONS: This study demonstrates an association
      between family physician continuity of care and the location of death for those
      with advanced cancer. Such continuity should be fostered in the development of
      models of integrated service delivery for end-of-life care.

PMID- 14733685
TI  - If it isn't depression.

PMID- 14733686
TI  - The explanatory model #26.

PMID- 14733687
TI  - Taking a spiritual history #19.

PMID- 14733689
TI  - Pseudoaddiction.

PMID- 14733691
TI  - Thinking outside the box: depression, hope, and meaning at the end of life.

PMID- 14733692
TI  - Reframing hope: meaning-centered care for patients near the end of life.
      Interview by Karen S. Heller.

PMID- 14733693
TI  - The FOOTPRINTS model of pediatric palliative care.
AB  - Little is known about the optimal context in which to provide care for the more
      than 53,000 children who die each year in the United States. Poor training in
      pediatric palliative care contributes to care that is often fragmented and may
      neglect the physical, psychosocial, and spiritual needs of the child and family.
      Pediatric hospice care is frequently not available or not chosen by the family or
      health care providers. In response to a critical need to move beyond the disease
      oriented, hospital-based model with a lack of continuity between hospital and
      community-based medical services, we developed FOOTPRINTS, an innovative program
      of advanced care planning and care coordination. A continuity physician directs
      the treatment plan regardless of site of care. Staff members coordinate follow up
      and communication among hospital and community-based care providers. Spiritual
      support continues through bereavement. Education in the hospital and community
      supports provision of excellent palliative care by current providers.
      Satisfaction with this model of care has been high. More than 90% of health care
      providers and families perceived that the child and family needs as well as the
      health care provider needs were met by the advanced care planning process and
      written care plan. All continuity providers would refer another patient. The
      FOOTPRINTS program promotes quality of care and family and health care provider
      satisfaction with care. It has been developed to serve as a "best practice" model
      for care at life's end.

PMID- 14733694
TI  - The PhoenixCare Program.
AB  - In response to a perceived need for patient access to palliative care and
      supportive services prior to hospice eligibility, Phoenix-based Hospice of the
      Valley (HOV) applied for and received a 3-year demonstration grant (1999-2001)
      from The Robert Wood Johnson (RWJ) Promoting Excellence in End-Of-Life Care
      Project. HOV established the PhoenixCare project as a demonstration of palliative
      and coordinated care (case management) services for seriously chronically ill
      individuals still undergoing active treatment of their disease within a managed
      care setting. The model emphasized patient/family self-empowerment and
      prevention. The goal was to demonstrate that it was possible to expand the scope
      of care for the seriously chronically ill, add palliative care, and improve
      patient quality of life at less (or no more) cost than that for a comparable
      group of managed care patients not receiving PhoenixCare services. The model
      proved most useful to patients willing and able to assume a degree of control
      over their own care. Physicians referred fewer than 5% of the patients enrolled
      while managed care plan case managers and hospital discharge planners referred
      83%, suggesting that in organized systems of care physicians are not a primary
      source for patient referrals. The structure and content of the PhoenixCare model,
      its general acceptability to patients, physicians and managed care plans, and its
      applicability to other sites are discussed in this article. Outcomes from the
      study will be published in a subsequent paper.

PMID- 14733695
TI  - Pressure-related hemodynamic effects of CO2 pneumoperitoneum in a model of acute
      cardiac failure.
AB  - BACKGROUND: The adverse effects related to CO2 pneumoperitoneum (PP) have been
      well documented. Although these effects in the state of cardiac failure have not
      been investigated, it appears to be common current clinical practice to use low
      pressure PP in this clinical setting, assuming it to be safer. OBJECTIVE: The aim
      of our study was to compare the hemodynamic changes with the application of
      conventional 15 mm Hg PP versus low-pressure 10 mm Hg PP in control and acute
      cardiac failure (ACF) animal models. METHODS: We studied changes in cardiac
      output (CO), stroke volume (SV), and systemic vascular resistance (SVR), applying
      10 mm Hg and 15 mm Hg CO2 PP in control and, following the pharmacological
      induction of acute cardiac failure, in 10 domestic pigs. RESULTS: In control, the
      application of 10 mm Hg PP did not cause any significant hemodynamic changes
      compared to baseline parameters. The use of 15 mm Hg PP in the model with normal
      cardiac function, however, produced a significant change in the tested
      hemodynamic values: CO decreased from 3.8L/min to 2.8L/min (P =.0018); SV
      declined from 38 mL to 30 mL (P =.046); SVR increased from 1677 dyne.s.cm-5 to
      2414 dyne.s.cm-5 (P =.049) compared to baseline. In the model of ACF induced by
      the intravenous infusion of sodium pentobarbital, the application of either 10 mm
      Hg or 15 mm Hg PP was found to have a similar hemodynamic trend: CO, 1.65 L/min
      vs. 1.41 L/min; SV, 23.2 L vs. 20.9 L; SVR, 2487 dyne.s.cm-5 vs. 2597 dyne.s.cm-5
      (P = NS for all). CONCLUSIONS: The application of low-pressure 10 mm Hg PP,
      compared to conventional 15 mm Hg PP, in the animal model of ACF does not appear
      to have any hemodynamic advantages.

PMID- 14733696
TI  - Laparoscopic wedge resection with handsewn closure for gastroduodenal tumors.
AB  - PURPOSE: To evaluate the feasibility and efficacy of laparoscopic wedge resection
      with handsewn closure in gastroduodenal tumors. METHODS: Laparoscopic wedge
      resection was performed in 16 patients with gastroduodenal tumor between May 2000
      and December 2002. Every case, except one, was performed via an extragastric
      approach; a transgastric approach was adopted in a single case. Excision of the
      lesion was performed manually by means of electrocautery or ultrasonic
      coagulating shears and closed by manual intracorporeal running suture. RESULTS:
      Among the 16 cases, two cases were treated using a laparoscope-assisted method,
      but there was no case of conversion to open surgery. Mean size of lesions was
      27.9 mm in diameter and the mean operation time was 219 minutes. In all cases, a
      complete tumor excision with negative surgical margins was obtained. The final
      pathologic diagnoses were ectopic pancreas (4 cases), gastrointestinal stromal
      tumor (3 cases), leiomyoma (2 cases), adenomyoma (2 cases), tubular adenoma (1
      case), Brunner's gland hyperplasia (1 case), carcinoid tumor (1 case),
      eosinophilic granuloma (1 case), and post-endoscopic mucosectomy state for early
      gastric cancer (1 case). The average numbers of days to first postoperative oral
      food intake and hospital stay were 3.1 days and 6.0 days, respectively. There
      were no postoperative complications. CONCLUSIONS: Laparoscopic wedge resection
      with handsewn closure should be considered as a valid treatment option for
      selected gastroduodenal tumors in terms of feasibility, safety, and cost. A more
      efficient surgical instrument and technique should be developed in future.

PMID- 14733697
TI  - Laparoscopic inferior mesenteric artery ligation: an alternative for the
      treatment of type II endoleaks.
AB  - One of the complications of endovascular repair of abdominal aortic aneurysm is
      endoleak from a patent inferior mesenteric artery (IMA). Between 1995 and 2002,
      of 213 patients who had endografts placed for abdominal aortic aneurysm, 4 (1.8%)
      had enlarging aneurysms from type II endoleaks involving a patent IMA and
      underwent a secondary procedure. Two patients had endovascular embolizations
      through the superior mesenteric artery, and two patients underwent laparoscopic
      inferior mesenteric artery ligation. In the laparoscopic group, operative time
      was 85 minutes (range, 35-136 minutes). One laparoscopic procedure had to be
      redone due to a missed IMA branch. Length of stay was 0 and 3 days. At mean
      followup at 16 months (range, 2-42 months), all patients had had successful
      resolution of endoleaks. Laparoscopic ligation is a minimally invasive treatment
      for IMA-mediated type II endoleaks.

PMID- 14733698
TI  - Grasper-assisted versus traditional laparoscopic splenectomy in the management of
      hematologic disorders.
AB  - OBJECTIVE: To compare the technical benefits of grasper-assisted laparoscopic
      splenectomy (LS) with traditional LS. METHODS: The study comprised 27 consecutive
      patients who were admitted to our hospital from 1998 to 2002 and underwent LS: 13
      patients underwent traditional LS (group 1), and 14 had grasper-assisted LS
      (group 2). RESULTS: In both groups, the most common indication for LS was
      idiopathic thrombocytopenic purpura. There was no difference between the groups
      in the demographic characteristics of patients. All splenectomies were performed
      in the right semidecubitus position, using four or five trocars. Conversion to
      open surgery was required in one patient (7.7%) in group 1 and in one patient
      (7.1%) in group 2. Both conversions occurred during the initial 16 operations and
      no conversion occurred during the subsequent 11 operations. The mean operating
      time was significantly shorter for group 2 (132 minutes) than for group 1 (154
      minutes) (P <.005). Mean estimated blood loss (201 vs. 282 mL) was also lower in
      group 2 than in group 1 (P <.05). The mean length of hospital stay was 3.3 days
      in group 1 and 2.4 days in group 2 (P >.05). CONCLUSION: Grasper-assisted LS is
      both safe and feasible in patients with hematologic diseases. This technique can
      be preferred in order to grasp and position the spleen during the surgery.

PMID- 14733699
TI  - Long-term results of transperitoneal laparoscopic fenestration in the treatment
      of simple renal cysts.
AB  - The aim of this paper was to assess long-term results of transperitoneal
      laparoscopic fenestration in the treatment of symptomatic simple renal cysts.
      Fifteen consecutive patients (7 men, 8 women), with a mean age of 51 years
      (range, 36-79 years), underwent transperitoneal fenestration of simple renal
      cysts (SRC) at our institution from 1994 to 2001. Data were collected by
      reviewing patients' clinical files, conducting telephone interviews regarding
      symptoms, and followup renal ultrasonography (US). There were 15 symptomatic
      cysts (10 parenchymal, 5 peripelvic) ranging in diameter from 3.5 to 20 cm (mean,
      8 cm). All patients had lumbar pain and in four (26.6%) the collecting system was
      compressed by the cysts. Fenestration was carried out laparoscopically in all
      patients. There was no mortality and no postoperative complications were
      recorded. No malignancies were detected at final histopathology. Mean length of
      stay was 2.5 days. All patients were available for long-term followup. At a mean
      of 60 months (range, 22-93 months) from surgery, three patients (20%) complained
      of slight discomfort in the lumbar area not requiring any analgesic. No
      recurrence of the cysts was seen on US. Two asymptomatic patients (13.3%)
      developed additional cysts originating from sites different than the one operated
      on. Laparoscopic fenestration of SRC is safe and effective in the long term to
      relieve patients from symptoms.

PMID- 14733700
TI  - Thoracoscopic localization techniques for patients with a single pulmonary nodule
      and positive oncological anamnesis: a prospective study.
AB  - INTRODUCTION: Our aim was to evaluate the best intrathoracoscopic localization
      technique in patients with a single pulmonary nodule and a history of malignancy.
      METHOD: We divided 30 patients into two groups, well matched for diameter and
      depth of the pulmonary lesion. In 15 patients (group A) we performed
      intrathoracoscopic ultrasound (US) to locate the pulmonary nodule, while in the
      other 15 patients (group B) intrathoracoscopic radioguided occult lesion
      localization (ROLL) was used. In both groups, the localization technique was
      compared to finger palpation. In group A, 6 nodules were in the left lung and 9
      in the right; in group B, 7 lesions were in the left and 8 in the right lung. In
      each group, the distance of the nodule from the pleural surface was 2-2.5 cm in 8
      patients, and > 2.5 cm in the remaining 7. In both groups, the diameter of the
      nodule was </= 1 cm in 6 patients, and 1-1.5 cm in 9 patients. All patients
      underwent thoracoscopic wedge resection, and 6 patients with a primary pulmonary
      lesion underwent posterior-lateral thoracotomy for lobectomy and mediastinal
      lymphadenectomy. RESULTS: In group A, US localized the nodule in 15 of 15
      patients (100%) while finger palpation located the nodule in 11 of 15 (73%) (P =
      NS). In group B, both ROLL and finger palpation localized the nodule in 12 of 15
      patients (80%) (P = NS). CONCLUSION: Intrathoracoscopic US seems superior to
      radioguided and finger palpation localization techniques for single pulmonary
      nodules. Thus, we are now routinely using intraoperative US to identify single
      pulmonary nodules.

PMID- 14733701
TI  - A comparison of laparoscopic bipolar vessel sealing devices in the hemostasis of
      small-, medium-, and large-sized arteries.
AB  - INTRODUCTION: The development of new energy sources for hemostasis has
      facilitated advanced laparoscopic procedures. Few studies, however, have
      documented the strength of the vessels sealed or the extent of surrounding
      lateral thermal injury, two important factors in maintaining hemostasis while
      preventing injury to surrounding structures. This study compared the burst
      pressure and extent of thermal injury of vessels sealed with the 5-mm
      laparoscopic PlasmaKinetics trade mark sealer (PK) (Gyrus Medical, Maple Grove,
      Minnesota) and the 5-mm laparoscopic LigaSure trade mark sealing device (LS)
      (Valleylab, Boulder, Colorado). METHODS: Arteries in three sizes (2-3 mm, 4-5 mm,
      and 6-7 mm) were harvested from domestic pigs. Eight to 17 specimens from each
      size were randomly sealed with the PK, and the same number with the LS. Burst
      pressures were measured in mm Hg. The extent of thermal injury, determined by
      coagulation necrosis, was measured microscopically in millimeters after staining
      the transected vessels with hematoxylin and eosin. Descriptive statistics,
      including means and standard deviations, are reported. Student's t-test and ANOVA
      were performed to determine significance (P <.05). RESULTS: The mean bursting
      pressures of the PK and the LS were equal in the 2-3 mm vessels (397 vs. 326 mm
      Hg, P =.49). The PK bursting pressures were significantly less than the LS in the
      4-5 mm (389 vs. 573 mm Hg, P =.02) and the 6-7 mm groups (317 vs. 585 mm Hg, P
      =.0004). As vessel size increased, the PK was associated with significantly lower
      burst pressures, while the LS was associated with progressively higher burst
      pressures (P =.035). Thermal spread was not significantly different between the
      PK and the LS in the 2-3 mm (1.5 vs. 1.2 mm, P =.27), the 4-5 mm (2.4 vs. 2.4 mm,
      P =.79), or the 6-7 mm vessel size groups (3.2 vs. 2.5 mm, P =.32). Increasing
      vessel size, regardless of instrument used, was associated with increased thermal
      injury (P <.0001). CONCLUSION: The LS produces supraphysiologic seals with
      significantly higher bursting pressures than the PK in vessels ranging from 4 to
      7 mm. The PK seals become progressively weaker while the LS seals increase in
      strength as the vessel size increases. Although thermal spread increases with
      vessel size, the degree of lateral thermal injury is no different between the two
      instruments.

PMID- 14733702
TI  - Laparoscopic fundoplication in children with a preexisting gastrostomy.
AB  - BACKGROUND: Children with a gastrostomy may require laparoscopic fundoplication
      (LF). METHODS: Children with a gastrostomy who underwent LF between 1998 and 2002
      were reviewed. The outcomes of children undergoing LF were compared with a group
      of children without a gastrostomy who had the same operation during the same
      period. RESULTS: Ten children with a gastrostomy in place and eight children
      without a gastrostomy underwent LF. The median operating time was 198 minutes
      (range, 115-300 minutes) in the gastrostomy group and 110 minutes (range, 80-130
      minutes) in the non-gastrostomy group (P =.002). In the gastrostomy group, two
      children had ventriculoperitoneal shunts and two had extensive intra-abdominal
      adhesions due to peritonitis. One laparoscopic procedure in each group was
      converted to an open approach. A successful LF was performed in nine of the ten
      children without taking down the gastrostomy. One child with a gastrostomy
      experienced recurrent vomiting that was managed with a gastrojejunal tube. One
      child in the non-gastrostomy group required reoperation due to an esophageal
      stricture. CONCLUSION: It seems that LF can be performed safely and effectively
      in children with a preexisting gastrostomy. LF in children with a gastrostomy
      seems to be as efficacious as LF in children without a gastrostomy.

PMID- 14733703
TI  - Surgical skill facilitation in videoscopic open surgery.
AB  - The operating room (OR) was traditionally characterized as a closed environment,
      in which the view of the operative field was available to the surgeon and
      assistant only. In laparoscopy, integration of technology into the surgical
      theatre has transformed surgical procedures into minimally invasive events, with
      viewing of the surgical field using endoscopic cameras. Similar technical
      advances to the open surgical environment will allow visualization and
      coordination of finer surgical maneuvers on standard video monitors. The
      objective of this study was to develop optimal protocols for performing basic
      open surgical maneuvers without direct viewing of the operating field, instead
      watching a monitor that displays the image of the surgical field captured by an
      endoscopic camera. The AESOP robotic arm and Alpha Virtual Port (Computer Motion,
      Goleta, California) were used to hold the endoscopic camera in different
      positions relative to the surgeon and the operative table. The surgeons
      conducting the study evaluated six such different setups. Based on the average
      time to complete the task in each of these setups and the ease of adaptation to
      the new working conditions, we concluded that at least one of these setups could
      be translated into the OR. The advantages of integrating video image enhancement
      over classical open surgery (OS) are that the surgical field can be magnified to
      perform finer maneuvers, and to share views of the surgical field with additional
      clinicians and trainees.

PMID- 14733704
TI  - Laparoscopic small bowel resection of metastatic pulmonary carcinosarcoma.
AB  - Carcinosarcoma of the lung is a rare malignancy consisting of both epithelial and
      mesenchymal components. Although metastatic disease is common, metastatic disease
      to the small intestine is rare and has been reported only once in the literature.
      An unusual case of pulmonary carcinosarcoma with metastasis to the small bowel is
      presented. At the time of laparoscopic exploration, a 4 x 4 cm mass was seen in
      the jejunum involving the adjacent mesentery. The affected small bowel and
      mesentery were resected laparoscopically and bowel continuity was restored
      through an entirely intracorporeal technique. Laparoscopic small bowel resection
      can be performed safely in the setting of malignant disease and imparts many of
      the benefits of minimally invasive surgery.

PMID- 14733705
TI  - Laparoscopic treatment of recurrent dysphagia following transthoracic myotomy for
      achalasia.
AB  - BACKGROUND: The choice of treatment of recurrent dysphagia following
      transthoracic myotomy is unclear. Often pneumatic dilatation is tried first,
      followed by esophagectomy in case of failure. We propose laparoscopic Heller
      myotomy as an alternative treatment for this group of patients. METHODS: Three
      patients underwent laparoscopic Heller myotomy for the treatment of recurrent
      dysphagia following transthoracic myotomy. The patients had undergone an average
      of 7 pneumatic dilatations (range, 2 to 10) prior to referral for surgery,
      without resolution of their dysphagia. RESULTS: All patients successfully
      underwent a laparoscopic myotomy on the right side of the esophagus with a Dor
      fundoplication. Good or excellent results were achieved in all patients. Average
      followup was 18 months. CONCLUSIONS: Laparoscopic Heller myotomy is a very
      effective treatment for patients who experience recurrent dysphagia following a
      transthoracic myotomy.

PMID- 14733706
TI  - Laparoscopic left hepatic lobe cholecystectomy.
AB  - Left sided gallbladders are rare and this case describes cholecystectomy without
      additional port placement.

PMID- 14733707
TI  - Self-expanding metallic stents in the management of lower gastrointestinal
      hemorrhage.
AB  - A case of an 82-year-old woman is reported who developed a lower gastrointestinal
      hemorrhage secondary to metastatic ovarian carcinoma to the colon. The bleeding,
      associated with an incomplete obstruction of the large bowel, was successfully
      treated with the endoscopic insertion of two self-expanding metal stents. A
      technique of stent placement is presented which differs from that previously
      reported, where both stents were via colonoscopy and without the use of
      fluoroscopy.

PMID- 14733708
TI  - Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding
      affinities and selectivities, and agonist potencies at FP and other PG receptors
      in cultured cells.
AB  - Natural prostaglandins (PGs) such as PGD2, PGE2, PGF2(2alpha), and PGI2 exhibited
      the highest affinity for their respective cognate receptors, but were the least
      selective agents when tested in receptor binding assays. Travoprost acid ([+]
      fluprostenol) was the most FP-receptor-selective compound, exhibiting a high
      affinity (Ki = 35 +/- 5 nM) for the FP receptor, and minimal affinity for DP (Ki
      = 52,000 nM), EP1 (Ki = 9540 nM), EP3 (Ki = 3501 nM), EP4 (Ki = 41,000 nM), IP
      (Ki > 90,000 nM), and TP (Ki = 121,000 nM) receptors. Travoprost acid was the
      most potent PG analog tested in FP receptor functional phosphoinositide turnover
      assays in the following cell types: human ciliary muscle (EC50 = 1.4 nM), human
      trabecular meshwork (EC50 = 3.6 nM), and mouse fibroblasts and rat aortic smooth
      muscle cells (EC50 = 2.6 nM). Although latanoprost acid exhibited a relatively
      high affinity for the FP receptor (Ki = 98 nM), it had significant functional
      activity at FP (EC50 = 32-124 nM) and EP1 (EC50 = 119 nM) receptors. Bimatoprost
      acid was less selective, exhibiting a relatively high affinity for the FP (Ki =
      83 nM), EP1 (Ki = 95 nM), and EP3 (Ki = 387 nM) receptors. Bimatoprost acid
      exhibited functional activity at the EP1 (EC50 = 2.7 nM) and FP (EC50 = 2.8-3.8
      nM in most cells) receptors. Bimatoprost (nonhydrolyzed amide) also behaved as an
      FP agonist at the cloned human FP receptor (EC50 = 681 nM), in h-TM (EC50 = 3245
      nM) and other cell types. Unoprostone and S-1033 bound with low affinity (Ki =
      5.9 microM to > 22 microM) to the FP receptor, were not selective, but activated
      the FP receptor. In conclusion, travoprost acid has the highest affinity, the
      highest FP-receptor-selectivity, and the highest potency at the FP receptor as
      compared to the other ocular hypotensive PG analogs known so far, including free
      acids of latanoprost, bimatoprost, and unoprostone isopropyl ester.

PMID- 14733709
TI  - The efficacy and safety of dose escalation of dorzolamide used in combination
      with other topical antiglaucoma agents.
AB  - We investigated the dose-escalation profile of dorzolamide used in combination
      with other antiglaucoma agents in patients with primary glaucoma and ocular
      hypertension. In a prospective, open-label study, 78 patients received
      dorzolamide 0.5% in addition to other topical antiglaucoma agents for > or =4
      weeks. The concentration of dorzolamide was then escalated to 1.0% and
      intraocular pressure (IOP) measured every 4 weeks for 12 weeks. Dose escalation
      of dorzolamide from 0.5% to 1.0% resulted in a significant reduction in IOP
      throughout the 12 weeks of treatment at the higher dose. Mean baseline IOP was
      19.7 mmHg. At 4, 8, and 12 weeks after dose escalation, mean IOP had decreased to
      17.8 (-9.4%), 17.6 (-10.8%), and 17.5 (-10.7%) mmHg. No serious drug-related
      adverse effects were reported. These results indicate that dose escalation of
      dorzolamide from 0.5% to 1.0% is effective and well tolerated as adjunctive
      therapy for patients in whom IOP is insufficiently controlled by combination
      therapy.

PMID- 14733710
TI  - Topical application of a nitric oxide synthase inhibitor reduces intraocular
      pressure in rabbits with experimental glaucoma.
AB  - The role of nitric oxide (NO) in neuronal degeneration of glaucoma is well
      established, and drugs to inhibit NO production have been introduced in
      preclinical studies. The present experiments were made to investigate the
      pharmacological efficacy of a topical formulation of the nonselective nitric
      oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), in an
      experimental model of glaucoma in rabbits. L-NAME was dissolved in an isotonic,
      mucoadhesive, viscosized, buffered solution in concentrations of 0.1%, 0.5%, or
      1% (w/v). Ocular hypertension (of at least 15 mmHg compared to basal values) was
      induced by intra-ocular injection of alpha-chymotrypsin. The instillation of L
      NAME topical formulations lowered the IOP of hypertensive rabbits in a dose
      related manner, with a maximum drop of 12.0 mmHg 60 minutes after administration
      of the highest concentration. The area under the curve (AUC) of the DeltaIOP
      (mmHg) versus time (minutes) was 1050.3 +/- 141.7 and 15.1 +/- 2.5 for the 1% L
      NAME-treated group and vehicle-treated group, respectively. No change was found
      in IOP or pupil diameter after instillation of L-NAME eye drops in normotensive
      rabbits. This study provides the first evidence that topical L-NAME significantly
      reduces the IOP in a model of ocular hypertension.

PMID- 14733711
TI  - Effect of ofloxacin and netilmicin on human corneal and conjunctival cells in
      vitro.
AB  - The purpose of this study was to compare the cytotoxic effects of the
      fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin. Human
      corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong
      Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0
      mg/mL) for 4 or 24 hours. Cell proliferation and viability were assessed with the
      MTT assay, neutral red uptake, and bromo deoxy uridine incorporation. In both
      cell lines, ofloxacin inhibited cell proliferation and viability. These effects
      were time and dose dependent. Concentrations of ofloxacin ranging from 0.4 to 2.4
      mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability.
      In contrast, netilmicin induced no toxic effect. The differences between
      ofloxacin and netilmicin were highly statistically significant (p < 0.001). This
      finding is particularly relevant in deciding the optimal antibiotic to be applied
      in clinical situations in which the epithelium is compromised.

PMID- 14733712
TI  - Corneal and scleral permeability of quinolones--a pharmacokinetics study.
AB  - PURPOSE: To investigate the corneal and scleral permeability of nalidixic acid
      and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits.
      METHODS: The corneal and scleral permeability coefficients of ciprofloxacin,
      norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using
      high performance liquid chromatography (HPLC). The aqueous humor levels of
      norfloxacin and ciprofloxacin were measured separately by topical instillation of
      0.3% solutions of the two drugs onto rabbit eyes. RESULTS: Nalidixic acid had a
      higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than
      all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits
      among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not
      significantly different (p > 0.1). Comparing the corneal and scleral permeability
      coefficients, only values for nalidixic acid were not significantly different
      (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p >
      0.05), while all other drugs had scleral permeability coefficients 8 to 10 times
      greater than corneal permeability coefficients. The mean aqueous humor
      concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after
      instillation was around 0.3 microg/mL, a value higher than MIC90 of most
      bacteria.

PMID- 14733713
TI  - Amylin competes for binding sites of CGRP in the chamber angle and uvea of
      monkey, cat, and pig eye.
AB  - Calcitonin gene-related peptide (CGRP) binding sites have been identified
      previously in the eyes of monkey, cat, pig, and guinea pig. In this study, the
      ability of cat, human, and rat amylins to displace the binding of CGRP in the
      anterior part of the eye of monkey, cat, and pig was studied. The location and
      displacement of 125I-hCGRPalpha by amylins as concentrations of 1-1000 nM were
      studied in cryosections by autoradiography. In the monkey eye, cat and rat
      amylins were able to compete for the binding sites of CGRP in ciliary muscle and
      ciliary processes. In the cat eye, cat and human amylins clearly displaced CGRP
      binding from ciliary muscle, ciliary processes, iris, and chamber angle.
      Furthermore, rat amylin clearly displaced CGRP binding from ciliary muscle and
      ciliary processes. In the pig eye, cat, human, and rat amylins competed for the
      binding sites of CGRP in ciliary muscle, ciliary processes, iris, and limbal
      conjunctiva. Specific amylin receptors or the possible physiological role of
      amylin in the eye have not hitherto been reported. It seems, however, that amylin
      can bind to ocular CGRP receptors and thus probably plays a role in the
      regulation of the same functions as CGRP, (e.g., aqueous humor outflow).

PMID- 14733714
TI  - Effects of nonsteroidal anti-inflammatory drugs on experimental allergic
      conjunctivitis in Guinea pigs.
AB  - The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on experimental
      allergic conjunctivitis, induced by ocular challenge with antigen in actively
      sensitized guinea pigs, were investigated. NSAIDs reduced the increase in
      prostaglandin D2 (PGD2) and E2 (PGE2) in the ocular lavage fluid. The inhibition
      of NSAIDs to these increases was approximately 90%-95%. NSAIDs also lowered itch
      scratch response (ISR) to approximately one-third to one-half of the vehicle
      treated group. However, these drugs scarcely affected plasma exudation in the
      conjunctiva. Ketotifen, an H1 histamine receptor antagonist, inhibited both
      pathophysiological changes (inhibition: 70%-80%). However, this drug was less
      efficacious than NSAIDs in reducing PGD2 and PGE2 levels. Moreover, topical
      administration of histamine induced ISR and plasma exudation; in contrast, PGD2
      induced ISR exclusively. These results suggest that a part of antigen-induced ISR
      may be attributable to PGs. However, PGs may not play a key role in plasma
      exudation; other mediators such as histamine may be involved.

PMID- 14733715
TI  - Peroxisome proliferator-activated receptor agonists inhibit interleukin-1beta
      mediated nitric oxide production in cultured lacrimal gland acinar cells.
AB  - Development of dry eye disease often occurs in individuals with autoimmune
      disorders such as Sjogren's syndrome. The cause of dry eye in these patients is
      thought to be due, at least in part, to lymphocytic infiltration of the lacrimal
      glands, with subsequent loss of secretion of the aqueous component of tear film.
      How this lymphocytic infiltration leads to loss of secretion is not fully
      understood. We have previously shown that the proinflammatory cytokine,
      interleukin-1beta (IL-1beta), can stimulate the production of nitric oxide (NO)
      in cultured lacrimal gland acinar cells. It is possible that IL-1beta, produced
      by the infiltrating macrophages, stimulates production of inducible nitric oxide
      synthase (iNOS), and subsequently excessive production of NO. Peroxynitrate and
      other radical byproducts associated with excessive synthesis of NO may be
      detrimental to normal function of the lacrimal gland. Here we show that the
      peroxisome proliferator-activated receptor (PPAR)alpha and gamma agonists can
      inhibit NO production in cultured lacrimal gland acinar cells. Further, this is
      accomplished without loss of iNOS expression or tetrahydrobiopterin. These data
      suggest that the use of ointments or eye drops containing these PPAR agonists may
      provide an effective therapeutic intervention for the prevention of dry eye in
      Sjogren's syndrome patients.

PMID- 14733716
TI  - Angiotensin converting anzyme (ACE) activity in porcine ocular tissue: effects of
      diet and ACE inhibitors.
AB  - The aim of the present experiments was to determine angiotensin converting enzyme
      (ACE) activity in different parts of the porcine eye, and to examine whether an
      atherogenic diet influenced ACE activity. Female mini-pigs were fed a standard
      diet or a diet with high cholesterol to produce atherosclerosis. The animals were
      killed by an overdose of pentobarbital, and the eyes were enucleated and
      dissected into iris, ciliary body, retina, and choroid. Crude tissue homogenates
      were used for determination of ACE activity, which was done with a radioenzymatic
      assay. In pigs fed a normal diet, basal ACE activity was 18.1 +/- 1.6, 13.6 +/-
      1.9, 4.4 +/- 0.6, and 44.7 +/- 8.5 units/mg for iris, ciliary body, retina, and
      choroid, respectively. The ACE activities in ocular tissues from the pigs that
      had been fed an atherogenic diet were not significantly different. Nor was the
      ACE activity in the abdominal aorta and serum significantly different between the
      two groups. In both groups, the ACE inhibitors captopril and enalaprilat, caused
      a significant inhibition of the ACE activity in the choroid and ciliary body,
      with enalaprilat being more potent. In the retina, ACE activity was inhibited
      significantly only in the group fed a normal diet, whereas ACE activity in the
      iris was not significantly inhibited in either group. We did not find any
      differences in ACE activity between pigs fed a normal diet and pigs fed an
      atherogenic diet, which is in disagreement with previous studies that showed an
      increased ACE activity in aorta from atherosclerotic mini-pigs. The reason for
      this discrepancy is not clear, but lower cholesterol levels are one possibility.

PMID- 14733717
TI  - Glucose-deprivation-induced [3H]D-aspartate release from isolated bovine and
      human retinae.
AB  - The glucose deprivation-induced release of [3H]D-aspartate was studied in bovine
      and human retinas in a superfusion apparatus. [3H]D-aspartate release was
      significantly increased upon omitting glucose in the superfusion buffer. This
      effect was dependent on external Ca2+ because L- and N-type Ca2+-channel
      blockers, such as diltiazem (1 microM), nitrendipine (1 microM), and omega
      conotoxin (100 nM), significantly reduced the effect of glucose-deprivation
      induced release of [3H]D-aspartate. Furthermore, while glutamate receptor
      agonists (L-glutamate, N-methyl-D-aspartate, but not kainate) potentiated the
      effects of glucose deprivation, antagonists (MK-801, MCPG, ifenprodil, and L-AP3)
      at these receptors blocked the glucose deprivation-induced release process. Taken
      together, these studies have demonstrated that under conditions of glucose
      deprivation, as may happen during ischemic events in vivo, the retinal
      glutamatergic nerve endings and/or glial cells promote the efflux of [3H]D
      aspartate into the extracellular environment. This process appears to be receptor
      mediated and dependent on extracellular Ca2+ and is similar to previous reports
      pertaining to brain tissues.

PMID- 14733720
TI  - Hyperlipoproteinemic low-density lipoprotein receptor-deficient mice are more
      susceptible to sepsis than corresponding wild-type mice.
AB  - High circulating concentrations of lipoproteins have been shown to modify the
      cytokine response and reduce mortality after endotoxin or live bacterial
      challenge. Sepsis, however, is more complex than endotoxemia, and it is not clear
      whether elevated plasma lipoproteins will be protective. Previous studies have
      shown that the low-density-lipoprotein receptor deficient (LDLR-/-) mice with
      increased circulating LDL are protected against the lethal effects of endotoxemia
      and Gram-negative infection. We evaluated whether the LDLR-/- mice would be
      protected against the effects of sepsis induced by cecal ligation and puncture
      (CLP). Mortality was greater in LDLR-/-mice than in control C57Bl/6J mice. At 120
      h after inducing sepsis, 20% of the control mice survived whereas none of theLDLR
      /-mice were alive. Prior to inducing sepsis, serum concentrations of amyloid A
      protein and lipopolysaccharide binding protein (LBP) were significantly elevated
      in the LDLR-/-mice in comparison to the C57Bl/6J mice. Protein expression of
      sCD14 was also greater in the serum from the LDLR-/-mice than the C57Bl/6J mice.
      The elevated serum concentrations of LBP and CD14 were not associated with
      increases in the levels of liver CD14 mRNA and LBP mRNA. After inducing sepsis,
      serum concentration of interleukin (IL)-1beta was also significantly higher in
      LDLR-/-mice than in the control C57Bl/6J mice. These findings indicate that the
      LDLR-/-mice were more susceptible to the lethal effects of sepsis induced by CLP.
      The LDLR-/-mice also had higher serum concentrations of baseline, acute phase
      response proteins, SAA and LBP, and increased production of IL-1beta in response
      to CLP.

PMID- 14733721
TI  - Effects of bacterial cell wall components (PAMPs) on the expression of monocyte
      chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP
      1alpha) and the chemokine receptor CCR2 by purified human blood monocytes.
AB  - Regulation of chemokine production and the expression of chemokine receptors play
      an important role during inflammation and infectious diseases. The present study
      was designed to study the effects of five different bacterial cell wall
      components (PAMPs) on the production of MCP-1 and MIP-1alpha and the expression
      of CCR2 by highly purified human blood monocytes. All five PAMPs induced high
      expression of mRNA and protein synthesis of both chemokines. Generally, MCP-1
      mRNA and protein levels were higher than MIP-1alpha levels. Expression of MCP-1
      and MIP-1alpha differed both at the mRNA and at the protein levels, MIP-1alpha
      always showing a more rapid initial increase, attaining lower protein levels than
      MCP-1. Antibodies against CD14 significantly inhibited the inducing effects of
      all the PAMPs used. Antibody against TLR2 inhibited the chemokine production
      induced by LTA and AraLAM by more than 36% (P < 0.05) while chemokine production
      induced by Escherichia coli-LPS, purified E. coli-LPS and Neisseria meningitidis
      LPS was inhibited by more than 60% by antibody against TLR4 (P < 0.05). The
      inducing effects of all five PAMPs could be inhibited by rIL-4, rIL-10 and rIL
      13. rIL-4 was the most effective. Generally, IC(50) of these anti-inflammatory
      cytokines were lower for the MIP-1alpha than for the MCP-1 production. The cell
      surface expression of CCR2 was significantly down-regulated by all five PAMPs in
      addition to a decrease in cytosolic free calcium and binding of rMCP-1. We
      conclude that MCP-1 and MIP-1alpha as well as the MCP-1 receptor CCR2 will be
      substantially regulated upon monocyte contact with various cell wall components
      (PAMPs) from Gram-negative and Gram-positive bacteria as well as from
      mycobacteria.

PMID- 14733722
TI  - Structural basis for endotoxic and antagonistic activities: investigation with
      novel synthetic lipid A analogs.
AB  - Our early work using homogeneous synthetic preparations demonstrated the presence
      of a lipid A analog which antagonizes endotoxic activities of LPS and lipid A.
      The first example was a tetraacylated biosynthetic precursor, now known as
      precursor Ia or lipid IVa, that contains four 3-hydroxytetradecanoyl moieties
      linked to the bisphosphorylated disaccharide backbone common to the endotoxic
      hexa-acyl Escherichia coli lipid A. Various compounds with both endotoxic and
      antagonistic activities have subsequently been reported from either natural or
      synthetic sources, but little is known about the factors determining the type of
      the activities of the respective compounds. To approach this issue, we have
      synthesized a series of lipid A analogs with various numbers and chain lengths of
      acyl groups on the backbone. Some were prepared by the aid of a novel affinity
      separation procedure. The phosphate moieties were also synthetically replaced.
      Biological tests showed that at least three acyl groups are required for
      antagonistic activity but one or even both of the phosphates can be replaced with
      other acidic moieties without losing the activity. The effect of Kdo residues
      linked to lipid A is also briefly discussed. Molecular dynamics calculations
      reasonably explain possible conformations required for the biological activity.

PMID- 14733723
TI  - Immunoneutralization of procalcitonin as therapy of sepsis.
AB  - Prior studies have demonstrated that the prohormone, procalcitonin (ProCT), and
      its component calcitonin precursors (CTpr) are increased in the serum of septic
      patients, correlate with the severity of the illness, and persist for relatively
      long periods of time. Animal studies in septic hamsters have revealed that the
      administration of ProCT is toxic and that immunoneutralization with IgG that is
      reactive to this molecule significantly improves survival. A large animal model
      of a very rapidly lethal polymicrobial sepsis has been developed in the pig in
      order to measure continuous physiological and metabolic parameters and also to
      compare the effects in this animal of an immunoneutralization, which is performed
      late in the course of the disease, to an identical, but early, therapy. Based
      upon the physiological and metabolic parameters, the late therapy, which was
      initiated during the fourth hour at a time when pigs were nearly moribund, was
      found to be as beneficial as early therapy. In both late and early therapy, the
      only animals to survive at the predetermined time of euthanasia were those which
      had received immunoneutralization therapy.

PMID- 14733725
TI  - The dual role of LBP and CD14 in response to Gram-negative bacteria or Gram
      negative compounds.
AB  - Innate immunity initiates protection of the host organism against invasion of
      micro-organisms by specific recognition mechanisms. This article reviews the dual
      role of LBP/CD14 in innate immunity, focusing mostly on experiments performed in
      mice by the authors. LPS induces uncontrolled pro-inflammatory response that
      kills the host and is LBP- and CD14-dependent, as neutralization of LBP and CD14
      prevents lethal shock. However, surprisingly, the synthetic Pam3CysSerLys4
      bacterial lipoprotein from Escherichia coli (BLP), which is well tolerated in
      mice, kills the mice upon LBP or CD14 blockade. Furthermore, after blockade of
      LBP and CD14, the mice succumb to a challenge with virulent Klebsiella pneumoniae
      or Salmonella typhimurium. Therefore, host responses to Gram-negative bacteria
      are not identical to that of LPS or BLP. When the host is in the presence of
      virulent Gram-negative bacteria, the invading pathogens must be held in check by
      the innate immune system until a specific immune response is mounted. Under these
      conditions, LBP, CD14, and likely Toll-like receptors (TLRs) are a prerequisite
      to trigger a pro-inflammatory response of macrophages, which is crucial for
      keeping an infection under control. These studies indicate that we are very far
      from understanding how the innate system works and more work needs to be done
      concerning LBP, CD14 or TLRs. Therefore, caution should be the rule about the use
      of therapeutic approaches to block the pro-inflammatory response in Gram-negative
      infections.

PMID- 14733724
TI  - The LPS receptor generates inflammatory signals from the cell surface.
AB  - Bacterial lipopolysaccharides (LPSs) are recognized in mammals by a receptor
      complex composed of CD14, Toll-like receptor 4 (TLR4), and MD-2. The mechanism of
      TLR4 function remains to be elucidated. We constructed chimeric TLR molecules C
      terminally fused to fluorescent proteins and stably expressed these chimeric
      constructs in cells. Confocal microscopy revealed TLR4 to be expressed on the
      plasma membrane and the Golgi apparatus. Time-lapse confocal imaging showed rapid
      recycling of TLR4/CD14/MD-2 complexes between the Golgi and the plasma membrane.
      Membrane TLR4 engagement by antibody was sufficient to induce signaling and
      pharmacological disruption of the Golgi did not affect cellular responses to LPS.
      Thus, LPS signaling commences after LPS recognition by surface-expressed TLR4
      independent of LPS trafficking to the Golgi.

PMID- 14733726
TI  - An overview of clinical studies in healthy subjects and patients with severe
      sepsis with IC14, a CD14-specific chimeric monoclonal antibody.
AB  - An overview and discussion of clinical studies with IC14, a chimeric monoclonal
      antibody directed against human CD14 is presented. These studies include phase 1
      trials in: (i) healthy subjects; (ii) healthy subjects challenged with
      lipopolysaccharide (LPS); and (iii) patients with severe sepsis. The results from
      clinical studies of IC14 demonstrate this chimeric monoclonal antibody diminishes
      the systemic inflammatory response directed against LPS and may have potential as
      a treatment to prevent organ dysfunction in patients with severe sepsis.
      Furthermore, IC14 treatment was generally well-tolerated in both healthy subjects
      and severe sepsis patients and did not increase the incidence of secondary
      infections. Analysis of pharmacology data indicate that higher doses of IC14 are
      required to saturate membrane-bound CD14 receptors effectively in patients with
      severe sepsis than in healthy subjects. Finally, the results of non-clinical
      studies indicate that IC14 should only be administered with concurrent
      antimicrobial therapy in patients with infection.

PMID- 14733727
TI  - Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel
      role for TLR4 and endosymbiotic Wolbachia bacteria.
AB  - Infection with the parasitic nematode Onchocerca volvulus is associated with
      inflammation of the skin and cornea that can lead to blindness. Corneal damage is
      thought to occur as a result of the host inflammatory responses to degenerating
      microfilariae in the eye. We have utilized a murine model of corneal inflammation
      (keratitis) to investigate the immune and inflammatory responses associated with
      river blindness. Soluble extracts of O. volvulus, a filarial species that
      contains the endosymbiont bacteria Wolbachia or Acanthocheilonema viteae (a
      nematode not naturally infected with the bacteria) were injected into mouse
      corneas. Inflammatory responses and corneal changes were measured. We
      demonstrated a major role for endosymbiont Wolbachia bacteria and Toll-like
      receptor 4 (TLR4) in the pathogenesis of ocular onchocerciasis.

PMID- 14733728
TI  - Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like
      receptor 4.
AB  - Lipid A is the pro-inflammatory component of bacterial lipopolysaccharide, the
      major surface component of Gram-negative bacteria. Gram-negative bacteria alter
      the structure of lipid A in response to specific environmental conditions
      including those found upon colonization of a host. The opportunistic pathogen
      Pseudomonas aeruginosa synthesizes a unique hexa-acylated lipid A containing
      palmitate and aminoarabinose during adaptation to the cystic fibrosis airway.
      Different lipid A species are observed in P. aeruginosa isolated from non-cystic
      fibrosis associated infections. Here we report that P. aeruginosa isolates from
      the airway of a cystic fibrosis patient with severe pulmonary disease synthesized
      a novel hepta-acylated lipid A. Cystic fibrosis-specific P. aeruginosa lipid A
      modifications result in resistance to host antimicrobial peptides and increased
      recognition by human Toll-like receptor 4 (TLR4). Using P. aeruginosa lipid A
      with different levels of acylation, we identified a 222 amino acid region in the
      extracellular portion of human TLR4 that is required for the differential
      recognition of cystic fibrosis-specific lipid A. P. aeruginosa adaptation to the
      human airway may, therefore, play a fundamental role in the progressive lung
      damage associated with cystic fibrosis.

PMID- 14733729
TI  - Regulation of interactions of endotoxin with host cells.
AB  - Potent Toll-like receptor 4 (TLR4)-dependent cell activation by endotoxin
      requires lipopolysaccharide-binding protein (LBP) and CD14-dependent delivery of
      endotoxin to cells containing MD-2 and TLR4. We have used metabolically labeled
      [(14)C] meningococcal lipooligosaccharide (LOS), purified recombinant endotoxin
      binding proteins, and cultured endothelial cells to better define
      protein:endotoxin intermediates key in cell activation in the absence of
      functional membrane (m) CD14. Protein:endotoxin complexes or aggregates (agg)
      were purified by gel sieving and characterized by immunocapture and bio-assays.
      Cell activation closely correlated with LBP, albumin and soluble (s) CD14
      dependent conversion of endotoxin agg (M(r) > or = 20 x 10(6)) to monomeric (M(r)
      approximately 55 x 10(3)) endotoxin:sCD14 complexes. Ordered interaction of LBP
      (+ albumin) and sCD14 with LOSagg was required for the efficient formation of a
      bioactive endotoxin:sCD14 complex and potent cell activation. Increasing the
      ratio of LBP/sCD14 or addition of bactericidal/permeability-increasing protein
      (BPI) reduced accumulation of endotoxin:sCD14 complexes and instead yielded
      aggregates of endotoxin (M(r) approximately 1-20 x 10(6)) containing LBP or BPI
      that were taken up by cells in a CD14- and TLR4-independent manner without
      inducing pro-inflammatory responses. These findings strongly suggest that host
      machinery linked to TLR4-dependent cellular activation or TLR4-independent
      cellular clearance of endotoxin selectively recognizes different
      protein:endotoxin complexes. At the outset of infection, the low concentrations
      of LBP present and absence of extracellular BPI favor formation of pro
      inflammatory endotoxin:CD14 complexes. The mobilization of LBP and BPI that is
      triggered by inflammation directs endotoxin for clearance and hence resolution of
      endotoxin-triggered inflammation.

PMID- 14733730
TI  - Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway.
AB  - The innate immune system is activated by infection and injury to release pro
      inflammatory cytokines, which activate macrophages and neutrophils and modulate
      specific cellular responses. The magnitude of the cytokine response is critical,
      because a deficient response may result in secondary infections, while an
      excessive response may be more injurious than the original insult. We recently
      described a neural pathway, termed the "cholinergic anti-inflammatory pathway",
      that reflexively monitors and adjusts the inflammatory response by inhibiting pro
      inflammatory cytokine synthesis. Efferent signals in the vagus nerve provide a
      direct mechanism for neural regulation of the immune response that is rapid,
      localized, and integrated. Vagus nerve stimulation inhibits the release of TNF,
      HMGB1, and other cytokines, and protects against endotoxemia and ischemia
      reperfusion injury. This newly identified physiological mechanism of maintaining
      immunological homeostasis suggests that novel therapeutics may effectively
      modulate inflammatory responses by activating the cholinergic anti-inflammatory
      pathway.

PMID- 14733732
TI  - Mucosal AIDS vaccines.
AB  - Debates are still being waged over what is the best strategy for developing a
      potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been
      tried in the past two decades without much success. It is clear that new thinking
      and a revision of prevailing dogmas needs to be in place if we really want a
      vaccine. Conventional envelope-based antibody-inducing vaccines do not appear to
      hold promise, and broadly-neutralizing antibodies are now being searched as an
      alternative to the failed approach with subunit vaccines. The current consensus
      is that cellular immune responses, especially those mediated by CD8
      cytotoxic/suppressor (CTL) and CD4 helper T lymphocytes, are needed to control
      HIV. Vaccines capable of inducing cell-mediated responses are, therefore,
      considered critical for controlling the spread of HIV. DNA-based vaccines
      triggering CTL reaction are currently thought to be an answer, but will they
      fulfill the promise? In the following paragraphs, a critical assessment of the
      state of the art will be provided in an attempt to analyze what we know and still
      don't know. The focus of this review is primarily on mucosal vaccines-a
      relatively new area in AIDS research. The update on V-1 Immunitor, the first
      mucosal AIDS vaccine available commercially, is provided within this context.
      Some of the reviewed concepts may be disputable, but without departure from the
      uninspiring consensus no substantial progress in the AIDS vaccine field can be
      envisioned.

PMID- 14733733
TI  - The role and regulation of COX-2 during viral infection.
AB  - Prostaglandins are lipid mediators, generated by cyclooxygenase (COX), that have
      been shown to participate in the regulation of virus replication and the
      modulation of inflammatory responses following infection. A number of studies
      support a role for PGE2 in the modulation of virus replication and virulence in a
      cell type and virus selective manner. Virus infection also stimulates the
      expression of a number of proinflammatory gene products, including COX-2,
      inducible nitric oxide synthase (iNOS) as well as proinflammatory cytokines. This
      review will focus on the mechanisms by which proinflammatory prostaglandin
      production regulates virus replication and virulence. In addition, the signaling
      pathways that are activated during a virus infection, and that regulate
      proinflammatory gene expression in macrophages will be reviewed. Specific
      attention will be placed on the ability of virus infection to activate multiple
      signaling cascades (such as PKR, MAPK, iPLA2, NF-kappaB) and how these pathways
      are integrated in the regulation of individual target gene expression.

PMID- 14733734
TI  - SARS: lessons learned from other coronaviruses.
AB  - The identification of a new coronavirus as the etiological agent of severe acute
      respiratory syndrome (SARS) has evoked much new interest in the molecular biology
      and pathogenesis of coronaviruses. This review summarizes present knowledge on
      coronavirus molecular biology and pathogenesis with particular emphasis on mouse
      hepatitis virus (MHV). MHV, a member of coronavirus group 2, is a natural
      pathogen of the mouse; MHV infection of the mouse is considered one of the best
      models for the study of demyelinating disease, such as multiple sclerosis, in
      humans. As a result of the SARS epidemic, coronaviruses can now be considered as
      emerging pathogens. Future research on SARS needs to be based on all the
      knowledge that coronavirologists have generated over more than 30 years of
      research.

PMID- 14733735
TI  - Innate immunity to herpes simplex virus type 2.
AB  - Herpes simplex virus type 2 (HSV-2) is responsible for most cases of genital
      herpes and also can cause fatal disseminated disease in perinatally infected
      newborns. Sexually transmitted infections initiate in the skin or mucosa and
      quickly spread into peripheral nerves to establish latency. Innate immunity, the
      first line of defense during both primary and recurrent infection, is essential
      during this period of acute infection to limit initial viral replication and to
      facilitate an appropriate adaptive immune response. The innate immune response
      consists of a complex multilayered system of mechanical and secreted defenses,
      immediate chemokine and IFN responses, and rapidly recruited cellular defenses.
      HSV has devised equally elaborate strategies to evade or interfere with innate
      immunity. This review summarizes our current understanding of the innate immune
      responses to HSV-2 and the mechanisms by which HSV-2 can overcome these barriers.
      Newly emerging links between products of innate responses and the development of
      adaptive immune responses are also discussed.

PMID- 14733736
TI  - Avidity maturation following immunization with two human cytomegalovirus (CMV)
      vaccines: a live attenuated vaccine (Towne) and a recombinant glycoprotein
      vaccine (gB/MF59).
AB  - Two human cytomegalovirus (CMV) vaccines have been previously evaluated for their
      immunogenicity: a recombinant gB/MF59 vaccine and an attenuated strain of CMV
      (Towne). In healthy adults, we measured the antibody avidity maturation indices
      that occurred after vaccination with each. For Towne, administered as a single
      dose, the rise in IgG antibody avidity to CMV glycoprotein gB occurred slowly and
      continued for 24 months post-immunization. For gB/MF59, administered as two
      priming doses and a booster dose given at 6 months, the booster rapidly induced
      IgG antibodies to gB whose avidity was maximal at 7 months after the initial
      priming dose. Both vaccines induced antibody levels and avidity maturation
      indices that equaled those induced by wild-type virus suggesting that both
      vaccines may be effective in controlling CMV infections.

PMID- 14733737
TI  - Interferon-containing supernatants increase Marek's disease herpesvirus genomes
      and gene transcription levels, but not virion replication in vitro.
AB  - Viruses encounter the innate immune system immediately after infection of the
      host; specifically, soluble molecules that are both directly lethal and that
      initiate acquired immunity. Using the oncogenic Marek's disease alpha-herpesvirus
      (MDV) model, we quantified the effect of a interferon-containing supernatants
      (ICS), on MDV replication, gene transcription and antigen expression kinetics. We
      used an established cell culture system and a well-defined virulent MDV (RB-1B).
      RB-1B was cultured without ICS, or pretreated and then continuously treated with
      ICS. We compared (i) RB-1B infectivity; (ii) RB-1B growth by microscopy; (iii)
      numbers of cells expressing RB-1B antigens by flow cytometry; (iv) RB-1B-DNA load
      per cell by duplex real-time PCR, and (v) gene transcription kinetics for key MDV
      life stages by duplex real-time reverse-transcriptase PCR (RT-PCR). ICS inhibited
      RB-1B infection, completion of productive life cycle and cell-to-cell infection.
      The numbers of cells expressing glycoprotein B (a kinetically late antigen)
      greatly decreased, but the numbers of cells expressing pp38 (a kinetically early
      antigen) decreased only slightly. The two greatest effects were increases in both
      RB-1B-DNA per infected cell and pp38 mRNA. We propose MDV has evolved to increase
      specific gene transcription and genome copies per cell to compensate for ICS. We
      speculate that the bi-directional shared pp38/origin of replication promoter, is
      central to this mechanism.

PMID- 14733738
TI  - Hydrophobic IgG-containing immune complexes in the plasma of autoimmune MRL/lpr
      mice, lactate dehydrogenase-elevating virus-infected mice, and pigs: association
      with transforming growth factor-beta and pH-dependent amplification.
AB  - Persistent infection of mice with lactate dehydrogenase-elevating virus (LDV) is
      associated with polyclonal B cell activation, autoimmunity, and circulating
      hydrophobic IgG-containing immune complexes (ICs), which bind to the surfaces of
      uncoated ELISA plates in the presence of 0.05% Tween 20. We demonstrate here that
      hydrophobic IgG-containing ICs also appear naturally in the plasma of autoimmune
      MRL/lpr mice. These and the similar hydrophobic ICs of LDV-infected mice as well
      as pigs coincide on ELISA plate surfaces with TGF-beta, apparently in the form of
      an IgG-TGF-beta complex. Circulating hydrophobic IgG-containing ICs are also
      susceptible to considerable amplification in vitro by exposure to alkaline
      conditions. By this latter method, the fraction of in vivo hydrophobic IgG,
      relative to the maximum in vitro chemically inducible IgG, was found to be about
      20% in the plasma of LDV-infected mice, 5% in normal mouse plasma, and less than
      about 2% in pig plasma. These results indicate the potential for both chemically
      induced and protein-binding contributions to the generation of hydrophobic IgG
      containing molecules, and have implications for immunopathological mechanisms in
      autoimmunity and persistent virus infections.

PMID- 14733739
TI  - Segregation of mechanisms for cytotoxic T lymphocyte killing between lungs and
      regional lymph nodes subsequent to intratracheal delivery of adenovirus 2 vector.
AB  - Recombinant adenovirus (Ad) vectors, highly effective for targeting the
      respiratory epithelium, have been investigated for proposed application in
      mucosal immunization. For rendering successful use of Ad vectors, it is
      imperative to understand the host immune responses in affected organs. We
      investigated the mechanisms of cytotoxic T lymphocyte (CTL) killing following
      intratracheal instillation with recombinant Ad2/betagal-2 vector. From the
      analysis of CTL responses, it became apparent that the lung CTLs were more Fas
      dependent, whereas pulmonary lymph nodes (LN) and splenic CTLs were more perforin
      dependent. Although there was a segregation in the mode of CTL killing, both
      mechanisms of cytolysis were used in the described tissues, and the observed
      dominance in CTL killing was maintained irrespective of the target evaluated.
      Restimulation of LN and spleen cells did not change dominance in the CTL
      mechanism utilized. Absence or blockage of perforin or Fas did not result in
      reciprocal compensation by the other effector mechanism except in Fas ligand
      deficient LN and spleens. In vitro restimulation of immune lymphocytes from each
      mouse group tested showed segregation in the types of cytokines generated. Ad2
      restimulated cells showed bias toward IL-2 and IFN-gamma, while betagal
      restimulated cells showed bias toward IL-4 and IL-10.

PMID- 14733740
TI  - Chitin Micro-Particles (CMP): a useful adjuvant for inducing viral specific
      immunity when delivered intranasally with an HIV-DNA vaccine.

PMID- 14733741
TI  - Special methods issues.

PMID- 14733742
TI  - Introduction to cloning by nuclear transplantation.
AB  - Despite its long history, the cloning of animals by nuclear transplantation is
      going through a "renaissance" after the birth of Dolly. The amount of work and
      achievements obtained in the last seven years are probably greater than those
      obtained in half a century of research. However, the principal obstacles outlined
      years ago with the work on somatic cell cloning in amphybia, are all still there
      in mammals. The importance of somatic cell nuclear transfer is, without any
      doubt, beyond the scope of replicating superior animal genotypes. It is an
      invaluable experimental tool to address fundamental scientific issues such as
      nuclear potency, cell de-differentiation, chromatin structure and function,
      epigenetics, and genome manipulation. For these reasons the importance of cloning
      is not for what it can achieve but for the technical support it can provide to
      biomedical research and in particular to the study of epigenetics, cancer and
      stem cell biology, cell therapy and regenerative medicine. In this introductory
      paper we will summarize the intellectual and technical framework of cloning
      animals by nuclear transfer that still remains the only absolute way of judging
      the success of the procedure. Together with the achievements of the recent past
      we will mention the very last developments and the many questions that still
      remain open. Current research efforts are expected to provide some answers and
      certainly new questions.

PMID- 14733743
TI  - Production of cloned pigs by using somatic cells as donors.

PMID- 14733744
TI  - Cloning cattle.
AB  - Over the past six years, hundreds of apparently normal calves have been cloned
      worldwide from bovine somatic donor cells. However, these surviving animals
      represent less than 5% of all cloned embryos transferred into recipient cows.
      Most of the remaining 95% die at various stages of development from a predictable
      pattern of placental and fetal abnormalities, collectively referred to as the
      "cloning-syndrome." The low efficiency seriously limits commercial applicability
      and ethical acceptance of somatic cloning and enforces the development of
      improved cloning methods. In this paper, we describe our current standard
      operating procedure (SOP) for cattle cloning using zona-free nuclear transfer.
      Following this SOP, the output of viable and healthy calves at weaning is about
      9% of embryos transferred. Better standardization of cloning protocols across and
      within research groups is needed to separate technical from biological factors
      underlying low cloning efficiency.

PMID- 14733745
TI  - A comparison of established and new approaches in ovine and bovine nuclear
      transfer.
AB  - Several breakthroughs in nuclear transfer research were first achieved in sheep,
      although cattle soon became the main livestock species of interest. However,
      sheep still offer significant advantages both in basic and applied research. With
      increased interest in cloning of livestock, new approaches have been developed
      for both sheep and cattle nuclear transfer technology. These include methods for
      zona-free nuclear transfer that can be performed with or without the use of
      micromanipulator. Here we describe four different nuclear transfer methods
      including the traditional micromanipulation-assisted method in sheep, zona-free
      method in sheep in which the order of enucleation and nucleus delivery have been
      reversed ("reverse-order" cloning) and zona free manual cloning methods ("hand
      made cloning") for embryonic and somatic cloning in cattle. The purpose of this
      paper is to encourage people to familiarize themselves with these different
      methods available and to help them choose and test the method most suitable for
      their particular circumstances.

PMID- 14733746
TI  - Nuclear transfer in goats using in vitro matured oocytes recovered by
      laparoscopic ovum pick-up.

PMID- 14733747
TI  - Cloning of mice by nuclear transfer.

PMID- 14733748
TI  - Production of cloned rabbits by somatic nuclear transfer.

PMID- 14733750
TI  - Nuclear transfer in the rhesus monkey: opportunities and challenges.

PMID- 14733749
TI  - Cloning companion animals (horses, cats, and dogs).

PMID- 14733751
TI  - Protocol for nuclear transfer in zebrafish.

PMID- 14733752
TI  - Reprogramming in inter-species embryonal carcinoma-somatic cell hybrids induces
      expression of pluripotency and differentiation markers.
AB  - Somatic cell reprogramming holds great promise for the development of novel
      cellular therapeutics. A number of sources of reprogramming potential have been
      identified, including oocytes, embryonic germ (EG) cells and embryonic stem (ES)
      cells. However, each of these sources of reprogramming factors is problematic,
      since they are either not freely available or have special growth requirements.
      Embryonal carcinoma (EC) cells are another source of pluripotent cells that,
      unlike ES and EG cells, do not usually require special growth conditions. Since
      they share many of the key characteristics of ES cells, such as pluripotency, EC
      cells may provide a readily amenable alternative source of reprogramming factors
      and could serve as a model for ES cells in this respect. Here we show that mouse
      EC cells can also function as donors of reprogramming factors. PEG-mediated
      fusion between murine EC cells (P19) and the cells of a human T-lymphoma cell
      line (CEM-GFP) resulted in inter-species hybrid colony formation. Colonies of
      hybrid cells displayed heterogeneity in cellular morphology as well as in their
      pattern of human gene expression. Expression of two human transcription factors
      characteristic of undifferentiated pluripotent stem cells, Oct-4 and Sox-2, was
      detected in the hybrid cells, demonstrating activation of endogenous human
      markers of pluripotency. Simultaneously, down-regulation of CD45, a marker
      present in lymphocytic cells, was observed in some hybrids. The detection of
      human specific markers of differentiation, such as nestin, lamininbeta1, and
      collagen IValpha1, indicates that fusion resulted in reprogramming of the human
      cells to reflect the differentiation potential of the murine EC partner.

PMID- 14733753
TI  - In vitro and in vivo developmental competence of ovulated and in vitro matured
      porcine oocytes activated by electrical activation.
AB  - The objective of this study was to evaluate the in vitro and in vivo
      developmental competence of parthenogenetic (parthenote) pig embryos derived from
      ovulated and in vitro matured (IVM) oocytes. A total of four experiments were
      carried out. These demonstrated that the mean blastocyst rates from stimulated
      ovulated and IVM pig oocytes were not significantly different (61% vs. 46%, p >
      0.05) following in vitro culture. Both ovulated and IVM pig parthenotes were able
      to develop in vivo for 30 days. Parthenote fetuses collected 21 and 30 days post
      estrus were morphologically normal but significantly smaller and lighter than
      fertilized controls (p < 0.01). IVM pig parthenotes stopped development around 31
      days post estrus.

PMID- 14733754
TI  - Comparison of electro-fusion and intracytoplasmic nuclear injection methods in
      pig cloning.
AB  - This paper methodologically compares the electro-fusion (EF) and intracytoplasmic
      injection (ICI) methods, as well as simultaneous fusion/activation (SA) and
      delayed activation (DA), in somatic nuclear transfer in pigs using fetal
      fibroblast cells. Comparison of the remodeling pattern of donor nuclei after
      nuclear transfer by ICI or EF showed that a high rate (80-100%) of premature
      chromosome condensation occurred in both cases whether or not Ca2+ was present in
      the fusion medium. Formation of pseudo-pronuclei tended to be lower for nuclear
      transfer performed by the ICI method (65% vs. 85-97%, p < 0.05). In vitro
      developmental potential of nuclear transfer embryos reconstructed with IVM
      oocytes using the EF method was higher than that of those produced by the ICI
      method (blastocyst formation: 19 vs. 5%, p < 0.05), and it was not improved using
      in vivo-matured oocytes as recipient cytoplasts. Embryos produced using SA
      protocol developed to blastocysts with the same degree of efficiency as those
      produced under the DA protocol (11 vs. 12%). Use of the EF method in conjunction
      with SA was shown to be an efficient method for producing cloned pigs based on
      producing a cloned normal pig fetus. However, subtle differences in nuclear
      remodeling patterns between the SA and DA protocols may imply variations in their
      nuclear reprogramming efficiency.

PMID- 14733755
TI  - Effect of demecolcine and nocodazole on the efficiency of chemically assisted
      removal of chromosomes and the developmental potential of nuclear transferred
      porcine oocytes.
AB  - Brief treatment of metaphase II (MII) stage porcine oocytes with 0.4 microg/mL
      demecolcine in the presence of 0.05 M sucrose produces a membrane protrusion that
      contains a condensed chromosome mass. The present study examined the optimal
      conditions for demecolcine and nocodazole treatment in chemically assisted
      removal of chromosomes. When matured oocytes were treated with 0.1-0.4 microg/mL
      demecolcine for 60 min or with 0.4 microg/mL demecolcine for 30 min or 3
      microg/mL nocodazole for 30 or 60 min, more than 70% of oocytes had a membrane
      protrusion containing condensed chromosomes were located. There was no difference
      in the in vitro developmental potential of enucleated oocytes assisted by 0.1 and
      0.4 microg/mL demecolcine or 3 microg/mL nocodazole that received porcine somatic
      cells. After transfer to 10 recipients, however, two of six recipients that
      received demecolcine-treated enucleated eggs produced four healthy cloned
      piglets, but none of the four recipients of nocodazole-treated enucleated eggs
      produced piglets. Further studies are required to increase the successful
      development to term because the proportion of live piglets was low (4/2, 672,
      0.15%).

PMID- 14733756
TI  - Potential impact of population-based colorectal cancer screening in Canada.
AB  - Randomized controlled trials (RCT) have shown the efficacy of screening for
      colorectal cancer (CRC) using the faecal occult blood test (FOBT) with follow-up
      by colonoscopy. We evaluated the potential impact of population-based screening
      by FOBT followed by colonoscopy in Canada: mortality reduction, cost
      effectiveness, and resource requirements. The microsimulation model POHEM was
      adapted to simulate CRC screening using Canadian data and RCT results about test
      sensitivity and specificity, participation, incidence, staging, progression,
      mortality and direct health care costs. In Canada, biennial screening of 67% of
      individuals aged 50-74 in the year 2000 resulted in an estimated 10-year CRC
      mortality reduction of 16.7%. The life expectancy of the cohort increased by 15
      days on average and the demand for colonoscopy rose by 15% in the first year. The
      estimated cost of screening was $112 million per year or $11,907 per life-year
      gained (discounted at 5%). Potential effectiveness would depend on reaching
      target participation rates and finding resources to meet the demand for FOBT and
      colonoscopy. This work was conducted in support of the National Committee on
      Colorectal Cancer Screening.

PMID- 14733757
TI  - Colorectal Cancer Screening: A note of caution.

PMID- 14733758
TI  - Lifetime costs of colon and rectal cancer management in Canada.
AB  - Colorectal cancer is the second leading cause of cancer-related mortality among
      Canadians. We derived the direct health care costs associated with the lifetime
      management of an estimated 16,856 patients with a diagnosis of colon and rectal
      cancer in Canada in 2000. Information on diagnostic approaches, treatment
      algorithms, follow-up and care at disease progression was obtained from various
      databases and was integrated into Statistics Canada's Population Health Model
      (POHEM) to estimate lifetime costs. The average lifetime cost (in Canadian
      dollars) of managing patients with colorectal cancer ranged from $20,319 per case
      for TNM stage I colon cancer to $39,182 per case for stage III rectal cancer. The
      total lifetime treatment cost for the cohort of patients in 2000 was estimated to
      be over $333 million for colon and $187 million for rectal cancer.
      Hospitalization represented 65% and 61% of the lifetime costs of colon and rectal
      cancer respectively. Disease costing models can be important policy- relevant
      tools to assist in resource allocation. Our results highlight the importance of
      performing preoperative tests and staging in an ambulatory care setting, where
      possible, to achieve optimal cost efficiencies. Similarly, terminal care might be
      delivered more efficiently in the home environment or in palliative care units.

PMID- 14733759
TI  - Which cancer clinical trials should be considered for economic evaluation?
      Selection criteria from the National Cancer Institute of Canada's Working Group
      on Economic Analysis.
AB  - Rising health care costs, expensive new health care technologies and increasing
      patient expectations are placing huge pressures on the publicly funded health
      care system in Canada. As a result, policy makers need information on the cost
      and cost-effectiveness of new therapies in addition to their clinical benefits.
      In response to this need, the National Cancer Institute of Canada Clinical Trials
      Group (NCIC CTG) established a Working Group on Economic Analysis (WGEA) to
      provide advice on the economic evaluation of new cancer therapies. This article
      describes the WGEA's recommendations on which trials should be considered for
      concurrent analysis of economic, as well as related issues, such as the number of
      patients required for an economic analysis within a prospective clinical trial
      and the selection of participating centres. The recommendations in this document
      are meant to be pragmatic, as the WGEA recognizes that both the research funds
      and human resource capacity for this type of research in Canada are limited.
      These recommendations are currently guiding priority setting with regard to
      trials for economic evaluation in NCIC trials. Examples of how these
      recommendations have been applied to actual trials are presented.

PMID- 14733760
TI  - Cause-deleted health-adjusted life expectancy of Canadians with selected chronic
      conditions.
AB  - Health-adjusted life expectancy (HALE) is life expectancy weighted or adjusted
      for the level of health-related quality of life (HRQOL). Cause-deleted
      probabilities of dying were derived using the cause-eliminated life table
      technique and death data from vital statistics for Canada in 1998/99. Life
      expectancy for men and women in Canada was 76.0 and 81.5 years respectively; HALE
      was 67.9 years for men and 71.1 years for women. Cancer represented the greatest
      burden of disease in the population, and eliminating it would increase men's life
      expectancy to 79.6 years and women's to 85.1 years. HALE would rise to 70.7 years
      for men and 73.6 for women. The gain in life expectancy would be very small if
      osteoarthritis were eliminated, but there would be an overall gain in HALE of
      approximately 1.0 years for men and 2.5 years for women. HALE estimated for
      chronic conditions using a utility-based measure of HRQOL from population health
      surveys should be regarded as a valuable component of population health
      surveillance.

PMID- 14733761
TI  - Geographic variation in health services use in Nova Scotia.
AB  - To further our understanding of factors underlying geographic variation in health
      and the potential role of availability of and access to health services, we
      sought to quantify the geographic variation in health services use in the
      province of Nova Scotia. For the period 1996 to 1999 we examined the variation in
      the use of health services across 64 geographic areas in conjunction with health
      and socio-economic factors, using multilevel methods and empirical Bayesian
      estimates based on provincial physician billings and hospital separation records.
      We revealed moderate geographic variation in the use of family physician services
      and large variation in specialist and hospital services. In the two urban
      centres, Metropolitan Halifax and the Cape Breton Regional Municipality, use of
      specialist services was respectively 26.24% and 15.59% higher than the provincial
      average, and use of hospital services was respectively 21.55% and 37.67% higher.
      Geographic areas in which residents had better health were characterized by more
      use of family physician services and reduced use of specialist and hospital
      services. These associations seem to support policy strategies that aim to
      improve health and to reduce health care costs by investing in prevention and
      primary health care, and they highlight the potential implications of the
      shortage of family physicians across Canada.

PMID- 14733762
TI  - Using a linked data set to determine the factors associated with utilization and
      costs of family physician services in Ontario: effects of self-reported chronic
      conditions.
AB  - Evidence-based health care planning for persons with chronic conditions is
      difficult. Routinely collected data are not specific enough to obtain prevalence
      estimates for chronic conditions and accompanying health determinants, whereas
      available survey data do not provide accurate utilization and/or cost
      information. The purpose of this study was to determine the association of self-
      reported demographic factors (age, sex), access (having a regular doctor), socio
      economic factors (education/income) and need (comorbidity) with actual family
      physician costs for persons with arthritis/rheumatism, asthma, back pain, high
      blood pressure and migraines. Data from consenting Ontario respondents to the
      1994 Canadian National Population Health Survey were linked with provincial
      physician billing claims. More than half of Ontario adults aged 25 and over
      reported a chronic condition; 24% reported two or more. Age, sex, access, socio
      economic status and need were independently associated with family practice
      utilization and costs, and the magnitude of the effects varied by condition.
      Linked survey/administrative data can provide valuable information to assist in
      evidence-based health care planning.

PMID- 14733763
TI  - How does negative affectivity contribute to medically unexplained dyspnea?

PMID- 14733764
TI  - Minimally invasive medicine: a new theoretical system of medicine.

PMID- 14733765
TI  - Medically unexplained dyspnea: psychophysiological characteristics and role of
      breathing therapy.
AB  - BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and
      remains poorly understood. This study was conducted to investigate the
      psychophysiological characteristics of medically unexplained dyspnea and the
      efficacy of breathing retraining for these patients. METHODS: A group of patients
      with medically unexplained dyspnea were compared to patients with a variety of
      organic lung diseases and healthy subjects. In another group of patients, the
      influence of breathing therapy on complaints, anxiety, and breath-holding was
      evaluated for an average of 1.5 years. RESULTS: Patients with medically
      unexplained dyspnea reported more intense dyspnea than patients with a variety of
      organic lung diseases. Additionally, they were anxious and presented a broad
      range of symptoms in daily life and under challenge, for instance voluntary
      hyperventilation. More than one third of them qualified for panic disorder. They
      had shorter breath-holding time at rest, less increase in breath-holding time and
      higher chances of showing a "paradoxical" decrease of breath-holding time after
      hyperventilation. A combination of PaO2, forced expiratory volume in one second
      (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing
      retraining profoundly improved their symptoms and decreased the level of state
      and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation
      and the symptoms induced were also markedly decreased after therapy. Breath
      holding time was prolonged and PetCO2 in a representative group of patients
      increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to
      have the feature of a "psychosomatic" patient: an anxious patient with a wide
      variety of symptoms of different organ systems that do not have an organic basis.
      They can be distinguished from organic dyspnea using a small set of physiological
      and psychological measures. Breathing retraining turns out to be an effective
      therapy for those "difficult to treat patients".

PMID- 14733766
TI  - Comparison of clinical course of patients with severe acute respiratory syndrome
      among the multiple generations of nosocomial transmission.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is characterized by both an
      atypical pneumonia and efficient nosocomial transmission. However, it remains
      unknown whether the infectivity and the virulence of the pathogen will change
      throughout the successive transmission. This study was conducted to compare the
      clinical features and management regimens of patients with SARS among the
      multiple generations from nosocomial transmission initiated by a super-spreader.
      METHODS: The clinical data of 84 epidemiologically-linked SARS patients from a
      hospital outbreak were retrospectively studied. All patients, in whom a clear-cut
      transmission generation could be noted, had a direct or indirect exposure to the
      index patient and the epidemic successively propagated through the multiple
      generations of cases within a short period of time. RESULTS: There were 66 women
      and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of
      whom were health care workers. Detailed contact tracing identified 35 (41.7%)
      first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third
      generation cases. No statistical differences among the multiple generations of
      transmission were found in terms of age, gender, incubation period and length of
      hospital stay. With the advanced transmission generations, the initial
      temperature lowered, the number of cases with dry cough decreased. There were no
      statistical differences in the peak temperature and duration of fever, other
      accompanying symptoms, leucopenia; however, the time from initial pulmonary
      infiltrates to radiographic recovery shortened (P < 0.05). No differences were
      found in maximum number of lung fields involved, duration from the onset of fever
      to the occurrence of pulmonary infiltrates and time from the initial pulmonary
      infiltrate to its peak among the multiple transmission generations (P > 0.05). No
      statistical differences were found in modes of oxygen therapy and sorts of
      antibiotics prescribed among the various transmission generations (P > 0.05);
      however, as with the advanced transmission generations, the number of cases
      prescribed with methylprednisolone, human gamma-globulin, interferon-alpha,
      antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time
      from admission to starting these medication shortened (P < 0.05). CONCLUSIONS:
      There is no evidence that SARS infection will evolve or transmit within a fashion
      that permits it to become less powerful throughout the successive transmission
      within a short time.

PMID- 14733767
TI  - The effect of protein kinase C on voltage-gated potassium channel in pulmonary
      artery smooth muscle cells from rats exposed to chronic hypoxia.
AB  - BACKGROUND: Chronic hypoxia can cause pulmonary hypertension and pulmonary heart
      disease with high mortality. The signal transduction pathway of protein kinase C
      (PKC) plays an important role in chronic pulmonary hypertension. So it is
      necessary to investigate the effect of PKC on voltage-gated potassium (K+)
      channels in pulmonary artery smooth muscle cells of rats exposed to chronic
      hypoxia. METHODS: Male Wistar rats were randomly divided into a control group
      (group A) and a chronic hypoxia group (group B). Group B received hypoxia [oxygen
      concentration (10 +/- 1)%] eight hours per day for four consecutive weeks. Single
      pulmonary artery smooth muscle cells were obtained using an acute enzyme
      separation method. Conventional whole cell patch clamp technique was used to
      record resting membrane potential, membrane capacitance and voltage-gated K+
      currents. The changes in voltage-gated K+ currents before and after applying
      paramethoxyamphetamine (PMA) (500 nmol/L), an agonist of PKC, and PMA plus
      carbohydrate mixture of glucose, fructose and xylitol (GFX) (30 nmol/L), an
      inhibitor of PKC, were compared between the two groups. RESULTS: The resting
      membrane potential in group B was significantly lower than that of group A: 
      (29.0 +/- 4.8) mV (n = 18) vs -(42.5 +/- 4.6) mV (n = 35) (P < 0.01). But there
      was no change in membrane capacitance between the two groups: (17.9 +/- 4.6) pF
      (n = 40) vs (19.7 +/- 5.8) pF (n = 31) (P > 0.05). The voltage-gated K+ currents
      were significantly inhibited by PMA in group A, and this effect was reversed by
      GFX. However, the voltage-gated K+ currents in group B were not affected by PMA.
      CONCLUSIONS: The resting membrane potential and voltage-gated K+ currents in
      pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia
      decreased significantly. It seems that PKC has different effects on the voltage
      gated K+ currents of pulmonary artery smooth muscle cells under different
      conditions.

PMID- 14733768
TI  - Relationship between bone marrow-derived CD34 + cells expressing interleukin-5
      receptor messenger RNA and asthmatic airway inflammation.
AB  - BACKGROUND: Asthma is clinically related with the degree of eosinophilic
      inflammation. How asthmatic airway inflammation is affected is still poorly
      understood. So the effects of bone marrow-derived hematopoietic cells expressing
      CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+)
      on asthmatic airway inflammation were investigated. METHODS: Balb/c mice were
      sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model
      while control mice were sensitized and exposed to sterile saline. The mice were
      killed at different time points after being challenged by OVA and sterile saline.
      Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow
      (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells
      in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+)
      cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in
      PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in
      situ hybridization were used to investigate the hematopoietic cells with co
      localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The
      percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated. RESULTS: Twelve
      hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were
      significantly higher than those in the control group (P < 0.01). Twenty-four
      hours after OVA challenge, BALFEOS, PBEOS and BMCD34+IL-5R mRNA+ were elevated
      maximally, significantly different from those in the control group (P < 0.01).
      Forty-eight hours after OVA challenge, BALFEOS and BMCD34+IL-5R mRNA+ were still
      significantly higher than those of the controls (P < 0.01). The other markers
      reverted to normal. In 60 mice, BMCD34+IL-5R mRNA+ was closely correlated with
      the BALEOS, PBEOS, BMCD(34)(+) and BMCD(34)(+) (%) (P < 0.05). CONCLUSIONS: The
      amount of CD(34)(+) cells expressing IL-5R mRNA increased in the BM of asthmatic
      model mice, which favors eosinophilopoiesis and eosinophilic airway inflammation.
      A signal pathway exists between the lungs and the bone marrow, which is involved
      in the initiation and maintenance of asthmatic airway inflammation.

PMID- 14733769
TI  - Contribution of protein kinase C to passively sensitized human airway smooth
      muscle cells proliferation.
AB  - BACKGROUND: Airway smooth muscle proliferation plays an important role in airway
      remodeling in asthma. But little is known about the intracellular signal pathway
      in the airway smooth muscle cell proliferation in asthma. The objective of this
      paper is to investigate the contribution of protein kinase C (PKC) and its alpha
      isoform to passively sensitized human airway smooth muscle cells (HASMCs)
      proliferation. METHODS: HASMCs in culture were passively sensitized with 10%
      serum from asthmatic patients, with non-asthmatic human serum treated HASMCs used
      as the control. The proliferation of HASMCs was examined by cell cycle analysis,
      3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazoliumbromide (MTT) colorimetric
      assay and proliferating cell nuclear antigen (PCNA) immunofluorescence staining.
      The effect of PKC agonist phorbol 12-myristate 13-acetate (PMA) and PKC inhibitor
      Ro-31-8220 on the proliferation of HASMCs exposed to human asthmatic serum and
      non-asthmatic control serum was also examined by the same methods. The protein
      and mRNA expression of PKC-alpha in passively sensitized HASMCs were detected by
      immunofluorescence staining and reverse transcription-polymerase chain reaction.
      RESULTS: The percentage of S phase, absorbance (value A) and the positive
      percentage of PCNA protein expression in HASMCs passively sensitized with
      asthmatic serum were (16.30 +/- 2.68)%, 0.430 +/- 0.060 and (63.4 +/- 7.4)%
      respectively, which were significantly increased compared with HASMCs treated
      with control serum [(10.01 +/- 1.38)%, 0.328 +/- 0.034 and (37.2 +/- 4.8)%,
      respectively] (P < 0.05). After HASMCs were passively sensitized with asthmatic
      serum, they were treated with PMA, the percentage of S phase, value A and the
      positive percentage of PCNA protein expression were (20.33 +/- 3.39)%, 0.542 +/-
      0.065 and (76.0 +/- 8.7)% respectively, which were significantly increased
      compared with asthmatic serum sensitized HASMCs without PMA(P < 0.05). After
      HASMCs passively sensitized with asthmatic serum were treated with Ro-31-8220,
      the percentage of S phase, value A and the positive percentage of PCNA protein
      expression were (11.21 +/- 1.56)%, 0.331 +/- 0.047 and (38.8 +/- 6.0)%
      respectively, which were significantly decreased compared with asthmatic serum
      sensitized HASMCs without Ro-31-8220 (P < 0.05). The relative ratio of value A of
      PKC-alpha mRNA and the positive percentage of PKC-alpha protein expression in
      passively sensitized HASMCs were 1.23 +/- 0.10 and (61.1 +/- 9.4)% respectively,
      which were significantly increased compared with HASMCs treated with control
      serum [1.05 +/- 0.09 and (34.9 +/- 6.7)%, respectively] (P < 0.05). CONCLUSIONS:
      The proliferation of HASMCs passively sensitized with human asthmatic serum is
      increased. PKC and its alpha isoform may contribute to this proliferation.

PMID- 14733770
TI  - The signal transduction pathway in the proliferation of airway smooth muscle
      cells induced by urotensin II.
AB  - BACKGROUND: Human urotensin II (UII) is the most potent mammalian vasoconstrictor
      identified so far. Our previous study showed that UII is a potent mitogen of
      airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent
      manner. The signal transduction pathway of UII mitogenic effect remains to be
      clarified. This study was conducted to investigate the signal transduction
      pathway in the proliferation of ASMC induced by UII. METHODS: In primary cultures
      of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein
      kinase (MAPK) and calcineurin (CaN) induced by UII were measured. The effect of
      CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific
      inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively,
      to study the effect of PKC and MAPK on CaN. The cytosolic free calcium
      concentration induced by UII was measured using Fura-2/AM. RESULTS: UII 10(-7)
      mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P < 0.01),
      respectively, after incubating for 20 minutes. It increased CaN activity in a
      time-dependent manner, being 1.68 times as that of control for 24 hours (P <
      0.01). It promoted the cytosolic free calcium concentration increase of 18% (P <
      0.01). CsA 10(-6) mol/L and H7 50 micromol/L inhibited UII-stimulated CaN
      activity by 45% (P < 0.01) and 21% (P < 0.05), respectively, while PD98059 50
      micromol/L had no effect on CaN activity (P > 0.05). CsA 10(-6) mol/L inhibited
      UII-stimulated PKC activity by 14% (P < 0.05), while having no effect on MAPK
      activity (P > 0.05). CONCLUSIONS: UII increases cytosolic free calcium
      concentration and activates PKC, MAPK and CaN. The signal transduction pathway
      between PKC and CaN has cross-talk.

PMID- 14733771
TI  - Molecular biological analysis of genotyping and phylogeny of severe acute
      respiratory syndrome associated coronavirus.
AB  - BACKGROUND: SARS-CoV is the causative agent of severe acute respiratory syndrome
      (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong
      and Beijing of China, and other regions worldwide. SARS-CoV from human has shown
      some variations but its origin is still unknown. The genotyping and phylogeny of
      SARS-CoV were analyzed and reported in this paper. METHODS: Full or partial
      genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single
      nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by
      molecular biological, bioinformatic and epidemiological methods. RESULTS: There
      were 188 point mutations in the 33 virus full genomes with the counts of mutation
      mounting to 297. Further analysis was carried out among 36 of 188 loci with more
      than two times of mutation. All the 36 mutation loci occurred in coding sequences
      and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2
      domain of spike glycoprotein and nucleocapsid protein were lower (0.079% -
      0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene
      mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this
      small domain (120 bp) and 3 of 4 loci related to deletion mutation. By
      bioinformatics processing and analysis, the nucleotides at 7 loci of genome
      (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a
      novel definition is put forward that according to these 7 loci of mutation, 40
      strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T
      and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype.
      The two genotypes can be further divided into some sub-genotypes. These genotypes
      can also be approved by phylogenetic tree of three levels of 44 loci of mutation,
      spike glycoprotein gene and complete genome sequence. Compared to various strains
      among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin
      genotype is more closely related to SARS-CoV like-virus from animals. CONCLUSION:
      The results mentioned above suggest that SARS-CoV is responding to host
      immunological pressures and experiencing variation which provide clues,
      information and evidence of molecular biology for the clinical pathology, vaccine
      developing and epidemic investigation.

PMID- 14733772
TI  - Carotid remodeling of hypertensive subjects and polymorphism of the angiotensin
      converting enzyme gene.
AB  - BACKGROUND: This study was designed to investigate the relationships between
      changes in the structure and function of carotid arteries and angiotensin
      converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects.
      METHODS: Multiplex polymerase chain reaction amplification was used to evaluate
      the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode
      ultrasound examinations were performed to detect parameters of carotid artery
      remodeling. RESULTS: Intima-media thickness (IMT) was significantly different
      among the DD, ID and II genotypes of ACE (DD > ID > II, P < 0.05). Carotid
      internal diameter, distensibility and stiffness were similar among the DD, ID and
      II genotypes of ACE (P > 0.05) in hypertensive subjects. The frequency of the DD
      gene and D allele of ACE were higher in patients with thickening carotid than in
      patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P
      < 0.001). In multiple stepwise regression analysis, independent risk factors for
      increased carotid IMT in hypertensive subjects were ACE genotypes (P < 0.001),
      age (P < 0.001) and carotid internal diameter (P = 0.032). Moreover,
      triglycerides and total cholesterol were higher in patients with the DD genotype
      than in those with the II genotype (P < 0.05). CONCLUSIONS: The I/D polymorphism
      of the ACE gene was related to IMT, but not to internal diameter, distensibility
      and stiffness of the carotid in Chinese hypertensive subjects. ACE gene
      polymorphism was a main risk factor for increased carotid IMT. These results may
      imply that there is a link between lipid metabolism and ACE genotype polymorphism
      in Chinese hypertensive subjects.

PMID- 14733773
TI  - Combined stent and coil in endovascular treatment of intracranial wide-necked and
      fusiform aneurysms.
AB  - BACKGROUND: Wide-necked and fusiform aneurysms are challenges for interventional
      neuroradiologists and neurosurgeons since they may involve entire vessels or be
      irregular in shape, making is possible for Guglielmi detachable coil to protrude
      into the parent arteries. This study was to evaluate the endovascular treatment
      of intracranial wide-necked and fusiform aneurysms by using a combination of
      stents and coils. METHODS: From October 2000 to July 2001, eighteen patients with
      intracranial wide-necked or fusiform aneurysms were treated with intraluminal
      stenting in combination with endosaccular coiling. RESULTS: Stent placement and
      coil packing were technically successful in all patients. There were no
      complications related to the procedure except for the migration of the stent in
      four cases. The aneurysms were embolized with the coils after precise stenting,
      and total occlusion was obtained in 13 cases, neck remnants in 3, and loose
      occlusion in 2. All the patients recovered well. Short-term follow-up angiograms
      suggested patency of the parent arteries without recanalization. CONCLUSIONS: A
      combination of endovascular stenting and coil packing may be a favorable
      alternative for the treatment of intracranial aneurysms that are unsuitable for
      surgical clipping or coil embolization. Further study is necessary to assess the
      long-term outcome.

PMID- 14733774
TI  - Vagus nerve stimulation for refractory epilepsy: long term efficacy and side
      effects.
AB  - BACKGROUND: In general vagus nerve stimulation (VNS) can serve as an adjunctive
      treatment for patients with refractory partial-onset seizures. And we evaluated
      the long-term efficacy and safety of VNS in a group of Chinese patients with
      refractory epilepsy. METHODS: Of 127 patients with refractory epilepsy, 13
      patients who were not eligible for surgical intervention were implanted with the
      Cyberonics VNS system. Seizure frequency, physical examination and side effects
      profile were recorded at follow-up visits for a minimum of 18 months. RESULTS:
      Mean duration of treatment was 47.4 months, and the longest follow-up period was
      71 months. Mean baseline seizure frequency was 26.6 seizures per month. The mean
      percentage reductions in convulsions were 33.2%, 47.1% and 40.0% at 6, 12 and 18
      months, respectively. One patient became seizure free, and six (46%) had 50% or
      more reduction in seizure frequency. Response was poor (< 20% reduction) in five
      patients (39%). Side effects were uncommon. CONCLUSIONS: The effectiveness of VNS
      was sustained and was well tolerated but benefited only a sub-group of patients
      with intractable convulsions.

PMID- 14733775
TI  - Bladder tumors: dynamic contrast-enhanced axial imaging, multiplanar reformation,
      three-dimensional reconstruction and virtual cystoscopy using helical CT.
AB  - BACKGROUND: There have been few studies to evaluate the effects of helical CT on
      bladder tumor. This study was to evaluate the clinical applications of helical CT
      dynamic contrast-enhanced axial imaging, multiplanar reformation (MPR), three
      dimensional (3D) reconstruction and virtual cystoscopy (CTVC) in bladder tumors.
      METHODS: The precontrast and four-phase postcontrast helical CT scans were
      performed in 42 patients with bladder tumors confirmed by conventional cystoscopy
      and pathology. MPR, 3D and CTVC images were generated from the volumetric data of
      the excretory phase. The results were then compared with the findings of
      conventional cystoscopy and surgery in a double-blinded mode. RESULTS: The
      sensitivity of the axial, 3D and CTVC images in detecting the bladder tumors were
      90.8%, 76.9% and 95.4% respectively. The dynamic contrast-enhanced axial images
      could provide excellent intramural and extravesical information, and the accuracy
      in preoperative tumor staging was 87.7%. MPR could directly demonstrate the
      origin and extravesical invasions of the tumors and their relation to the ureter.
      3D and CTVC images were useful for displaying the surface morphology of the tumor
      and the relationship between the tumor and the ureteric orifices, whereas CTVC
      could depict the tumors smaller than 5 mm that were not seen on the axial images.
      CONCLUSIONS: The combination of axial, MPR, 3D and CTVC images with helical CT
      can provide comprehensive information on bladder tumor.

PMID- 14733776
TI  - Mass screening of 12,027 elderly men for prostate carcinoma by measuring serum
      prostate specific antigen.
AB  - BACKGROUND: The incidence of prostate carcinoma (Pca) has been increasing in
      China. We detected Pca in elderly men in Changchun, north China and the
      significance of prostate specific antigen (PSA) in mass screening and clinical
      staging of Pca. METHODS: Serum PSA from 12,027 men over 50 years old from
      Changchun was analyzed. In case of serum PSA greater than 4.0 ng/ml, the patient
      was suspected of potentially suffering from Pca, and transrectal six-point
      puncture prostate biopsies were performed under ultrasound guidance. Pathological
      examinations were performed on the biopsy tissue, and ABCD and TNM clinical
      stagings were used in accordance with international standards. Correlations
      between serum PSA level and clinical stage were analyzed. RESULTS: PSA was
      greater than 4.0 ng/ml in 813 patients (6.8% of the 12,027 men). Transrectal six
      point prostate puncture biopsies guided by ultrasound were performed in 273
      patients (33.6% of the 813 patients who were tested positive in the initial mass
      screening). Of these 273 patients, 69 cases of Pca (25.3% of 273) were confirmed
      by biopsy in the second screening, with an overall detection rate for Pca of
      0.57% (69/12,027). The total number of patients in stages A, B, T1, or T2 was
      57.9%, and over 20% of them suffered from late stage Pca with lymph node and bone
      metastasis. An obvious positive correlation was observed between ABCD staging,
      TNM staging, and serum PSA level. CONCLUSIONS: Serum PSA level is not only the
      golden standard for mass screening of Pca, but also the predictor for clinical
      stage of Pca. PSA testing revealed asymptomatic Pca cases in early, middle, and
      later stages in the elderly, suggesting that mass screening is of paramount
      importance.

PMID- 14733777
TI  - Polymorphisms of the coagulation factor VII gene and its plasma levels in
      relation to acute cerebral infarction differences in allelic frequencies between
      Chinese Han and European populations.
AB  - BACKGROUND: Coagulation factor VII (FVII) levels in plasma are usually related to
      ischemic heart disease (IHD) and cerebral infarction shares many of the risk
      factors related to IHD. Is there any relationship between factor VII and cerebral
      infarction? We investigated the relationship between FVII and acute cerebral
      infarction and reported genotype frequencies and allelic frequencies of FVII gene
      polymorphisms in the Chinese Han population. METHODS: We recruited 62 patients
      with acute cerebral infarction confirmed by magnetic resonance imaging (MRI) from
      Ruijin Hospital, and 149 age-matched patients clinically free of vascular disease
      to act as controls. All of them were unrelated, and were from the Chinese Han
      population. FVII coagulant activity (FVIIc) was determined using an clotting
      assay, activated FVII (FVIIa) and FVII Ag were assayed using enzyme immunoassay
      kits. The FVII gene polymorphisms to be detected included-401G/T, -402G/A,
      5'F7A1/A2, IVS7 and R353Q. 5'F7 and IVS7 were revealed by means of a PCR and
      direct agarose gel electrophoresis. The rest were examined by a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The
      results showed that FVIIc, FVIIAg and FVIIa were higher in the acute cerebral
      infarction group than in the control group (P < 0.01, P < 0.05, P < 0.05,
      respectively). There were no significant differences in the genotype frequencies
      of FVII gene polymorphisms between the two groups. The allelic frequencies in the
      Chinese Han population were as follows: -401G/T (96.64/3.36), -402G/A
      (52.01/47.99), 5'F7A1/A2 (96.64/3.36), IVS7 H5/H6/H7/H8 (0.34/52.35/46.98/0.34)
      and R353Q (95.64/4.36). There were significant differences (P < 0.01, P < 0.001,
      P < 0.001, P < 0.001, P < 0.001, respectively) in these allelic frequencies
      between the Chinese Han and European populations. CONCLUSIONS: The results
      indicate that increased plasma FVII levels may contribute to thrombosis in
      cerebral infarction. And there was no significant difference in genotype
      frequencies of these five FVII gene polymorphisms between the acute cerebral
      infarction and control groups. Moreover, these results showed that the
      frequencies of protective allele, including -401T, 5'F7 A2 and 353Q were lower,
      but that -402A, which was previously found to be associated with increased plasma
      FVII levels, is higher in Chinese Han population.

PMID- 14733778
TI  - Superselective uterine arterial embolization with pingyangmycin-lipiodol emulsion
      for management of symptomatic uterine leiomyoma.
AB  - BACKGROUND: Uterine arterial embolization (UAE) is a safe and effective therapy
      for symptomatic uterine leiomyoma. This study was to assess the effectiveness and
      the feasibility of pingyangmycin-lipiodol emulsion (PLE) for the management of
      symptomatic uterine leiomyoma. METHODS: One hundred consecutive patients (aged 21
      - 53 years, with 38 in average) with symptomatic uterine leiomyoma underwent
      superselective UAE with PLE. Clinical symptoms of the patients (including
      menorrhagia, bulk-related symptoms, and postprocedure-related abdominal pain) and
      the changes in uterine volume and tumor size after the embolization were
      analyzed. The patients were followed up for 8 - 21 months (mean, 15 months).
      RESULTS: Ninety-nine patients (99%, 99/100) were interviewed in their first
      menses circle after embolization, showing improvements in their abnormal bleeding
      and bulk-related symptoms to some extent. Imagiological results during follow-up
      showed a mean of 48% reduction in uterine volume at 6 months and a mean of 75%
      reduction in tumor size at 9 months. Eighty-three percent of the patients
      reported complete resolution of postprocedure pain within 7 days. CONCLUSIONS:
      PLE is effective in the management of uterine leiomyoma, having superiority in
      alleviating postprocedure-related pain.

PMID- 14733779
TI  - Expression of IFN-gamma and its receptor alpha in the peripheral blood of
      patients with chronic hepatitis C.
AB  - BACKGROUND: It has been known that intra-cellular immunity is important for
      defense against viral infections and this function lies with interferon gamma
      (INF-gamma). Here we evaluated the role of IFN-gamma system in the pathogenesis
      of chronic hepatitis C (CHC). METHODS: The levels of interferon gamma receptor
      alpha (IFNGR alpha) on the peripheral lymphocyte membrane were assayed with flow
      cytometry. The plasma concentrations of the cytokines IFN-gamma and IL-10 in CHC
      patients and normal controls were assayed by enzyme-linked-immunosorbent assay
      (ELISA). The samples were collected randomly from Xinjiang Autonomous Region,
      Zhejiang and the northern regions of Jiangsu Province in China. RESULTS: The
      levels of IFNGR alpha in CHC patients were significantly lower than that of
      normal controls (NC), especially among patients during the stable stage (P <
      0.001), whereas there were no significant differences between CHC in active and
      stable stages. Among the patients of the three regions, there were no significant
      differences between patients from Xinjiang and Zhejiang provinces, but both had
      statistically significant difference compared with the patients from Jiangsu
      Province (P < 0.001). Plasma IFN-gamma and IL-10 concentrations in CHC patients
      decreased significantly, IFN-gamma in particular, but there were no significant
      differences in these levels between various stages of the disease. The IFN
      gamma/IL-10 (Th1/Th2) ratio in patients was reversed. CONCLUSION: There may be
      defects in the IFN-gamma system in chronic HCV infected subjects and a low immune
      response, which may play an important role in the persistence of HCV infection.

PMID- 14733780
TI  - Nanoparticles as a vaccine adjuvant of anti-idiotypic antibody against
      schistosomiasis.
AB  - BACKGROUND: The development of new adjuvants for human use has been the focus of
      attention. This study's aim is to explore the possibility of using nanoparticle
      Ca nanoparticles (CA) as a vaccine adjuvant of anti-idiotypic antibody NP30
      against schistosomiasis and its protective mechanisms. METHODS: Nanoparticle CA
      NP30 conjugate (CA-NP30) was fabricated. BALB/c mice were immunized actively with
      CA-NP30 to evaluate its effects of protective immunity on mice. The serum levels
      of specific IgG, IgG1 and IgG2a antibodies against NP30 and the concentrations of
      IFN-gamma and IL-4 in supernatant of splenocytes were determined via ELISA.
      RESULTS: Nanoparticle CA could enhance significantly the protective immunity of
      NP30 against infection of Schistosoma japonicum and the worm reduction rose from
      36.0% (NP30 alone) to 52.6%. The serum levels of specific IgG, IgG1 and IgG2a
      antibodies against NP30 increased remarkably, as compared with those of the group
      immunized with NP30 alone. The concentration of IFN-gamma in supernatant of
      splenocyte was drastically elevated [the groups immunized with CA-NP30 and NP30
      alone were (493.80 +/- 400.74) pg/ml and (39.03 +/- 39.58) pg/ml, respectively],
      but the concentration of IL-4 showed no significant difference from that of NP30
      alone [(27.94 +/- 9.84) pg/ml vs (27.28 +/- 14.44) pg/ml]. CONCLUSIONS:
      Nanoparticle CA could act as a vaccine adjuvant of anti-idiotypic antibody NP30
      against schistosomiasis. The mechanism could be that CA-NP30 enhances humoral and
      cellular immune responses in mice.

PMID- 14733781
TI  - Angiotensin II induced upregulation of G alpha q/11, phospholipase C beta 3 and
      extracellular signal-regulated kinase 1/2 via angiotensin II type 1 receptor.
AB  - BACKGROUND: The role of the G alpha q/11-mediated signal transduction pathway in
      angiotensin II (AngII) induced cardiac hypertrophy remains unclear. This study
      was to investigate the role of the G alpha q/11 signal transduction pathway in
      the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured
      neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the
      pathway on AngII induced cardiac hypertrophy. METHODS: Renal hypertension was
      induced in 2K1C hypertensive rats by placing a silver clip around the left renal
      artery. At 8 weeks after operation, the systolic blood pressure, the ratio of
      left ventricular weight to body weight (LV/BW), and the concentration of AngII in
      the heart were measured. The protein levels of G alpha q/11 and extracellular
      signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and
      the activity of phospholipase C (PLC) in the myocardium was detected using [(3)H]
      PIP2 as a substrate. Changes in [(3)H]-leucine incorporation and in the protein
      levels of the signal molecules G alpha q/11, PLC beta 3, and ERK1/2 were measured
      after NRVMs were stimulated with 10(-7) mol/L AngII. RESULTS: The protein levels
      of G alpha q/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and
      31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C
      group was also significantly increased (P < 0.05). The levels of G alpha q/11,
      PLC beta 3, and ERK1/2 increased significantly after NRVMs were stimulated by
      AngII. The upregulation of G alpha q/11, PLC beta 3 and ERK1/2 in NRVMs occurred
      prior to [(3)H]-leucine incorporation increases, and could be inhibited with
      losartan. CONCLUSION: AngII can initiate cardiac hypertrophy and upregulate
      signal molecules in the G alpha q/11-mediated signal transduction pathway, such
      as G alpha q/11, PLC beta 3 and ERK1/2, at both tissue and cellular levels.

PMID- 14733782
TI  - Tumor blood vessels formation in osteosarcoma: vasculogenesis mimicry.
AB  - BACKGROUND: Osteosarcoma is characterized by high neovascularization and a high
      propensity for metastasis through bloodstream. This study was to examine whether
      there is evidence for vasculogenic mimicry in osteosarcoma and to illustrate
      mechanism of tumor blood vessels formation in osteosarcoma. METHODS: Osteosarcoma
      cell lines (U-2OS) were tested for their ability to form tubular networks in
      three-dimensional culture containing type I collagen. The structures of the
      tubular networks were observed with phase contrast microscope and transmission
      electron microscope (TEM). Morphometric studies using hematoxylin and eosin (HE)
      stain and CD31 immunohistochemical stain to show tumor-lined channels in human
      osteosarcoma were also performed. RESULTS: Observation with light microscope and
      TEM showed that highly aggressive osteosarcoma cell lines (U-2OS) formed networks
      containing channels when grown in three-dimensional culture containing type I
      collagen, in the absence of endothelial cells or fibroblasts. Morphometric
      observation using HE stain and CD31 immunohistochemical stain showed that tumor
      cell-lined channels were also detected in vivo in osteosarcoma; by comparison,
      all vascular areas in the pedicle of osteochondroma or outside osteochondroma
      were endothelial-lined. CONCLUSION: These observations strongly suggest that
      aggressive osteosarcoma cells may generate vascular channels that facilitate
      tumor perfusion independent of tumor angiogenesis and have the ability of
      vasculogenic mimicry.

PMID- 14733784
TI  - Intrabiliary radiation inhibits smooth muscle formation and biliary duct
      remodelling after balloon overstretching injury in dogs.
AB  - BACKGROUND: Internal metallic stents have been widely used in clinical practice,
      but a high postoperative restenosis rate limits its application. The purpose of
      this study was to determine the effect of intrabiliary radiation on muscle
      formation and biliary duct remodeling after biliary duct balloon injury in dogs.
      METHODS: Twenty male dogs (15 - 20 kg) were randomly divided into treatment group
      (n = 10) and control group (n = 10). Balloon overstretching injury was induced
      using a balloon catheter placed across the biliary duct. Subsequently, a 103Pd
      radioactive stent was positioned at the target site in each animal in the
      treatment group, providing the injured biliary duct with a radiation dose of
      12.58 x 10(7) Bq. Dogs in the control group received Ni-Ti stents. All the dogs
      were killed one month after initial injury. The injured sections were dissected
      free from the dogs, and were processed for histological and morphological study.
      Cross-sections were stained with hematoxylin-eosin, Masson's trichrome, and
      Verhoef-van Giesen. Muscle formation area and lumen area were determined using a
      computer-assisted image analysis system. RESULTS: Compared with the control
      group, 103Pd radioactive stents significantly reduced muscle formation area
      (78.3%, P < 0.01), and percentage area of stenosis [control stents: (60.0 +/-
      21.6)%, 103Pd radioactive stents: (31.6 +/- 9.5)%]. In addition, in the treatment
      group, the biliary duct lumen area was significantly larger than that in the
      control group (P < 0.01). CONCLUSIONS: 103Pd radioactive stents providing a
      radioactive dose of 12.58 x 10(7) Bq are effective in reducing muscle formation
      and biliary duct remodeling after balloon overstretching injury.

PMID- 14733783
TI  - 5-Aza-2'-deoxycitydine induces demethylation and up-regulates transcription of
      p16INK4A gene in human gastric cancer cell lines.
AB  - BACKGROUND: To investigate the effects of DNA methylation on the expression of
      tumor-associated genes and the cell cycle in human gastric cancer cells. METHODS:
      Two gastric cancer cell lines (MKN-45 and HGC-27) were treated with DNA
      methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC). The
      expressions of p16INK4A, p21WAF1, p53, p73, c-Ha-ras and c-myc genes mRNA were
      detected by using reverse transcription PCR (RT-PCR). DNA methylation status of
      p16INK4A gene promoter was assayed by bisulfite modification and sequencing. The
      cell cycle was analyzed by using flow cytometry (FCM). RESULTS: 5-aza-dC induced
      the demethylation of p16INK4A gene promoter. The expression of p16INK4A mRNA was
      obviously up-regulated by treatment with 10 micro mol/L (MKN-45 cells) or 5 micro
      mol/L (HGC-27 cells) of 5-aza-dC for 24 hours. However, 5-aza-dC treatment failed
      to regulate the expressions of p21WAF1, p53, p73, c-Ha-ras and c-myc genes in MKN
      45 and HGC-27 cells. Furthermore, 5-aza-dC induced the cell cycle arrest in G1
      phase in HGC-27 cell, but not in MKN-45 cell. CONCLUSIONS: DNA methylation
      regulates the transcription of p16INK4A but not p21WAF1 and proto-oncogenes in
      human gastric cancer cell lines MKN-45 and HGC-27.

PMID- 14733785
TI  - Macrophage migration inhibitory factor enhances neoplastic cell invasion by
      inducing the expression of matrix metalloproteinase 9 and interleukin-8 in
      nasopharyngeal carcinoma cell lines.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) shows highly invasive and metastatic
      features. This study aims to investigate macrophage migration inhibitory factor
      (MIF)-induced invasion of NPC cells in vitro and the effects on matrix
      metalloproteinases (MMPs) and interleukin-8 (IL-8), and to study the mechanism of
      tumor cell invasion and metastasis in the early stage of NPC. METHODS: Two
      nasopharyngeal carcinoma cell lines, CNE-1 and CNE-2, were adopted in this study.
      The NPC cell invasion and migration were evaluated by microinvasion assay. The
      variation of expression percentages of MMP2- or MMP9-positive cells was detected
      by flow cytometry in two cell lines with or without MIF treatment. Western
      blotting and RT-PCR were used to assay the protein and mRNA expressions of MMP2
      and MMP9. The IL-8 concentration secreted by NPC cells was compared with the
      cells with different treatments using ELISA. RESULTS: After treating with MIF for
      48 hours, the cell numbers of CNE-1 and CNE-2 which went through the 8-microm
      filter membrane were increased. Compared with non-MIF treated NPC cells,
      significant difference could be found both in CNE-1 (P = 0.005) and CNE-2 cells
      (P = 0.001). The percentages of MMP9-positive cells were significantly increased
      in both CNE-1 [from (28.5 +/- 2.5)% to (82.4 +/- 3.5)%, P = 0.001] and CNE-2
      [from (32.8 +/- 3.5)% to (86.1 +/- 1.6)%, P = 0.002]. The relative intensity of
      MMP9 protein expression was also enhanced in both cell lines (CNE-1: from 83.1 +/
      6.0 to 242.9 +/- 22.9, P = 0.002; CNE-2: from 84.4 +/- 4.3 to 278.9 +/- 29.7, P
      = 0.003). Correspondingly, the increased MMP9 mRNA expression level was
      significantly detectable in both cell lines. The concentration of IL-8 in the
      supernatant of CNE-2 was higher [(1201.8 +/- 593.3) pg/ml] after treatment. It
      was also remarkably higher than that in the supernatant of CNE-2 without
      treatment (P = 0.026). However, there was no significant difference in the
      concentration variation of IL-8 in CNE-1 (P = 0.581), while the IL-8 mRNA level
      was only enhanced in CNE-2. CONCLUSIONS: MIF can induce potent invasion of NPC
      cell lines in vitro, and the infiltrating lymphocytes in NPC might be responsible
      for the invasion and metastasis of tumor cells. MIF cytokine which is secreted by
      these infiltrating lymphocytes might contribute to the invasion as well as
      metastasis of NPC in the early stages by induction of MMP9 and IL-8 in an
      indirect pathway.

PMID- 14733786
TI  - Establishment and biological characteristics of human multiple myeloma cell line
      CZ-1.
AB  - BACKGROUND: There were only 3 multiple myeloma (MM) cell lines established in
      China. In this study, we succeeded in establishing a novel MM cell line and
      analyzed its biological characteristics. METHODS: Mononuclear cells isolated from
      the peripheral blood (PB) and bone marrow (BM) of a patient with advanced MM
      (lambda light chain type) were cultured in medium. Cell morphology was analyzed
      by Wright-Giemsa-staining and cytochemical staining, immunophenotyping by flow
      cytometry and cytogenetic analysis by chromosome RHG-banding technique.
      Quantitative fluorescent polymerase chain reaction (PCR) was used to detect
      Epstein - Barr virus (EBV) DNA. RESULTS: The established cell line could survive
      and proliferate in the presence of feeder cells or conditioned medium. The cells
      secreted lambda light chain and were negative for EBV. The Wright-Giemsa-staining
      showed typical plasmablast or plasma cell morphology. The cytochemical staining
      of the cells showed the following reactivity patterns: positive for acid
      phosphatase, negative for myeloperoxidase. The immunoprofile of the cells was
      concordant with that of MM cells: positive for CD10, CD28, CD38, CD138, CD56,
      CD49d, CD44, CD54 and CD58, negative for CD19, CD40, CD95, CD95L, CD34, CD2 and
      CD5. The cytogenetic analysis showed complex chromosome abnormality of i (1q+),
      8q+, 13q+, i (17q), i (18q) and +M. There was no difference in morphology,
      immunophenotype and cytogenetics between cells from PB and BM. CONCLUSIONS: An MM
      cell line secreting lambda light chain named CZ-1 was established. The cells from
      both PB and BM have the same biological characteristics.

PMID- 14733787
TI  - Prophylaxis of neonatal respiratory distress syndrome by intra-amniotic
      administration of pulmonary surfactant.
AB  - BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is caused by a
      deficiency in pulmonary surfactant (PS) and is one of the main reasons of
      neonatal mortality. This study was conducted to evaluate the efficacy and safety
      of intra-amniotic administration of pulmonary surfactant for prophylaxis of NRDS.
      METHODS: Forty-five pregnant women who were due for preterm delivery and whose
      fetuses' lungs proved immature were divided into two groups. Fifteen women (study
      group) were administered one dose of pulmonary surfactant injected into the
      amniotic cavity and delivered within several hours. Nothing was injected into the
      amniotic cavity of 30 women of the control group. The proportion of neonatal
      asphyxia, NRDS, mortality and the time in hospital were analyzed to determine if
      there was any difference between the two groups. RESULTS: There was no
      significant difference between the two groups for neonatal asphyxia. Foam tests
      showed that higher proportion of neonates in the study group than in the control
      group (56.3% vs 13.3%, P < 0.05) had lung maturity. A greater number of control
      neonates (11/30, 32.3%) had NRDS, compared with the neonates given PS via the
      amniotic cavity before delivery (1/16, 6.3%, P < 0.05). The neonates in the study
      group spent nearly 10 days less in hospital than the control group [(32.4 +/-
      7.6) days vs (42.0 +/- 15.7) days, P < 0.05], but the difference in mortality
      between the two groups was not statistically significant. CONCLUSIONS: Intra
      amniotic administration of pulmonary surfactant can significantly reduce the
      proportion of NRDS and the time in hospital of preterm neonates. Whether this
      method can reduce the mortality of preterm neonates needs to be evaluated
      further. Intra-amniotic administration of pulmonary surfactant provides an
      additional effectual means for NRDS prophylaxis.

PMID- 14733788
TI  - Influenza DNA vaccine: an update.

PMID- 14733789
TI  - The role of inflammatory stress in acute coronary syndrome.
AB  - OBJECTIVE: To summarize current understanding of the roles of anti-inflammatory
      and proinflammatory mechanisms in the development of atherosclerosis and acute
      coronary syndrome and to postulate the novel concept of inflammation stress as
      the most important factor triggering acute coronary syndrome. Moreover, markers
      of inflammation stress and ways to block involved pathways are elucidated. DATA
      SOURCES: A literature search (MEDLINE 1997 to 2002) was performed using the key
      words "inflammation and cardiovascular disease". Relevant book chapters were also
      reviewed. STUDY SELECTION: Well-controlled, prospective landmark studies and
      review articles on inflammation and acute coronary syndrome were selected. DATA
      EXTRACTION: Data and conclusions from the selected articles providing solid
      evidence to elucidate the mechanisms of inflammation and acute coronary syndrome
      were extracted and interpreted in the light of our own clinical and basic
      research. DATA SYNTHESIS: Inflammation is closely linked to atherosclerosis and
      acute coronary syndrome. Chronic and long-lasting inflammation stress, present
      both systemically or in the vascular walls, can trigger acute coronary syndrome.
      CONCLUSIONS: Inflammation stress plays an important role in the process of acute
      coronary syndrome. Drugs which can modulate the balance of pro- and anti
      inflammatory processes and attenuate inflammation stress, such as angiotensin
      converting enzyme (ACE) inhibitors/angiotensin II receptor blockers, statins, and
      cytokine antagonists may play active roles in the prevention and treatment of
      acute coronary syndrome when used in addition to conventional therapies
      (glycoprotein IIb/IIIa receptor antagonists, mechanical intervention strategies,
      etc).

PMID- 14733790
TI  - Nucleoprotein gene analysis of the wild-type measles viruses circulated in
      Beijing in 2001.

PMID- 14733791
TI  - Chest X ray changes in severe acute respiratory syndrome cases after
      discontinuation of glucocorticosteroids treatment.

PMID- 14733793
TI  - Laparoscopic radical prostatectomy.

PMID- 14733792
TI  - Hypoxia-inducible factor-1 alpha increased the expression of peroxisome
      proliferator activated receptor alpha in lung cancer cell A549.

PMID- 14733794
TI  - Verruciform xanthoma of the penis: report of a case.

PMID- 14733795
TI  - Intrasellar tuberculoma: case report.

PMID- 14733796
TI  - [SARS-associated coronavirus gene fragments were detected from a suspected
      pediatric SARS patient].
AB  - A Special "Fever and Cough" Clinic was set up at the Children's Hospital
      Affiliated to Capital Institute of Pediatrics for children with symptoms of fever
      and cough in late April when the severe acute respiratory syndrome (SARS)
      epidemic was at its peak in Beijing to separate the children with fever from
      others during their visit to the Outpatient Department. OBJECTIVE: For patients
      with fever, normal or low count of white blood cell and with suspected pneumonia
      suggested by X-ray, it was urgent to determine the etiological agents of the
      diseases before they were admitted to the hospital. METHODS: Throat swabs or
      nasopharyngeal aspirate specimens were collected from those patients and common
      respiratory virus antigens including influenza virus A and B, respiratory
      syncytial virus, adenovirus, parainfluenza virus types I, II, and III were tested
      by indirect immunofluorescent assay. The patients with atypical pneumonia
      diagnosed by X-ray and evidences of common respiratory virus infection were
      admitted to the regular ward for children with respiratory diseases. Children
      with pneumonia demonstrated by X-ray and negative for common respiratory viruses
      were admitted to the isolated ward for suspected SARS patients for the first step
      and further viral etiological studies were requested. RT-PCR was performed for
      those patients to detect gene fragments of human metapneumovirus (HMPV),
      rhinovirus (RhV) and enterovirus (EV) in their specimens. Nested RT-PCR was also
      developed to detect SARS coronavirus gene fragment from the specimens. Primer
      sequences for SARS virus detection with the PCR were selected according to the
      primer sequences published online by WHO on April 18, 2003. All the primers
      derived from the sequence at the 1b frame of coronavirus replicase gene and
      products with a size of 368 or 348 bp were expected with 2 different primer
      pairs. RESULTS: Amplicons with the sizes of 368 bp and 348 bp were obtained from
      a throat swab specimen collected from a 17 years old girl, who was admitted to
      the isolated ward because of high fever (39.5 degrees C) for 7 days, cough for 2
      days, low WBC count, and pneumonia shown by X-ray when she visited the "Fever and
      Cough" Clinic, and without known history of contact with probable SARS patient.
      Antigens for the common respiratory viruses were all negative, RT-PCR for HMPV,
      RhV and EV were also negative while RT-PCR with different primer pairs for SARS
      virus were all positive which indicated that SARS coronavirus gene fragments were
      amplified from the specimen from this girl. The amplified fragment with a size of
      368 bp was sequenced and the sequence was compared with those in the GenBank. The
      sequence shared 100% homology with the sequences from 1b frame of replicase genes
      from all 17 of SARS coronaviruses published in the GenBank so far, and shared
      very low homology with 2 reference strains of human coronavirus as well as other
      animal coronaviruses. The serum collected before her discharge from the hospital
      (19 days after the onset of the disease) showed SARS specific IgM and IgG
      antibodies. CONCLUSION: These data indicate that the patient was a confirmed case
      of SARS. It is of great importance to differentiate SARS patients from those
      infected with common respiratory viruses during SARS epidemic, especially for
      pediatric patients, because most of the patients visiting the outpatient
      department present with the symptoms of fever, cough and normal WBC count. The
      data mentioned above indicate that antigen and gene detections for those common
      respiratory viruses are useful methods for the differentiation to avoid the
      spread of SARS.

PMID- 14733797
TI  - [Clinical and chest X-ray characteristics of 5 cases with severe acute
      respiratory syndrome in children in Shenzhen area].
AB  - OBJECTIVE: To explore clinical and chest X-ray features of SARS in children to
      facilitate correct diagnosis. METHODS: Clinical manifestations and chest X-ray
      findings in five children suffering from SARS admitted for treatment in the
      hospital between February and May, 2003 in Shenzhen area were analyzed. The
      diagnosis was confirmed by epidemiological, clinical, laboratory and radiological
      examinations. Among the 5 cases, 1 was a boy and the others were girls at the age
      of 4 to 13 years. RESULTS: Of the 5 SARS children, 3 presented a history of close
      contact with SARS patients. Fever was the initiative symptom, 4 had a body
      temperature of over 38 degrees C with the highest being 40 degrees C; fever
      sustained from 4 to 7 days with an average of 5.6 days. All the 5 cases developed
      nonproductive cough; on auscultation, both moist and dry rales could be heard in
      3 out of the 5 cases. Mean total white count of peripheral blood was (2.96 - 6.9)
      x 10(9)/L, and was < 5.0 x 10(9)/L in 4 cases. SARS associated coronavirus
      specific RNA fragment was found positive by RT-PCR in 1 case; 1 case was positive
      for both IgM and IgG antibodies to the virus; 1 case was positive for only IgM
      antibody and another 2 cases were positive for only IgG antibody. IgG and IgM
      antibodies to Mycoplasma pneumoniae and Chlamydia pneumoniae as well as blood
      culture for bacteria were all negative. Findings on chest X-ray examination: 4
      cases showed presence of patchy or macular opacities with cord-like shadows in
      unilateral lung plates while 1 case each showed ground-glass-like opacity and
      migratory changes; 1 case showed interstitial changes in the lungs in the form of
      irregular reticular lattice and cord-like shadows. Two cases received CT scanning
      and macular-patchy or spotty shadows were seen all over the lung. The shortest
      time for absorption of foci in the lungs was 7 days while the longest was 33 days
      with a mean of 15 +/- 6 days. None of the cases had any signs of fibrosis in the
      lungs. All the 5 cases were completely cured and discharged 7 to 40 days (mean 18
      +/- 11 days) after admission. CONCLUSION: Compared with adult cases with SARS,
      children with SARS had milder symptoms and signs. Presence of unilateral patchy
      shadow in lungs represented the main chest X-ray findings.

PMID- 14733798
TI  - [Childhood SARS in Hong Kong].

PMID- 14733799
TI  - [Role of flexible bronchoscopy in the treatment of infection-associated
      atelectasis in children].
AB  - OBJECTIVE: Infection-associated atelectasis is rather common during childhood and
      the effects of drug therapy are often unsatisfactory. The present study aimed to
      evaluate the effectiveness of flexible bronchoscopy in the treatment of infection
      associated atelectasis in children. METHODS: One hundred and twenty-five patients
      (68 male and 57 female; age ranged from 10 d to 14 years and their courses of
      disease were from 3 d to 2.5 years) with infection-associated atelectasis
      confirmed by chest X-ray or CT were enrolled in the study. The following
      conditions were excluded by bronchoscopy: airway foreign body, airway anomalies,
      tumor, tuberculosis. The patients were divided into two groups: flexible
      bronchoscopy group and medication group. In the flexible bronchoscopy group, 65
      patients were treated mainly with flexible bronchoscopy whereas in medication 60
      group patients only received medication. Chest X-ray or CT was regularly reviewed
      for every patient, meanwhile the effect of flexible bronchoscopy at different
      courses of disease was observed. RESULTS: Flexible bronchoscopy group and
      medication group had no significant differences in age, sex and course of disease
      (P > 0.05). In flexible bronchoscopy group 39 patients were cured, 20 were
      improved and 6 cases had no change; in medication group 17 patients were cured,
      25 were improved and 18 had no change. The two groups had significant differences
      (P < 0.01); in bronchoscopy group there were significant differences among
      patients with the courses of disease less than 3 months, 3 to 6 months and more
      than 6 months. CONCLUSIONS: The authors concluded that flexible bronchoscopy was
      an effective method for treatment of infection-associated atelectasis. Flexible
      bronchoscopy can reach pathological part and clear pus and granulation. It can
      remove obstruction and relieve symptoms. When course of disease was short,
      bronchoscopic therapy was advantageous to recovery of atelectasis. Bronchial
      washing may overcome the shortcomings of bronchoalveolar lavage, therefore the
      former seemed to be more suitable for treatment of infection-associated
      atelectasis.

PMID- 14733800
TI  - [Three generations of a family allergic to vitamin C].

PMID- 14733802
TI  - [Report of a case with toxoplasmosis].

PMID- 14733801
TI  - [T(H1) and T(H2) cells in children with mycoplasma pneumonia].
AB  - OBJECTIVE: To Study T lymphocyte subsets, including T(H1) and T(H2) cells in
      peripheral blood mononuclear cells (PBMC) of children with mycoplasma pneumonia,
      understand immunopathogenesis and explore the possibility of immunotherapy of
      patients with mycoplasma pneumonia. METHODS: Fresh peripheral blood samples of
      patients from two groups, group 1, mycoplasma pneumonia (MP) group (35 cases, 15
      males and 20 females, age range 3 - 13 years, mean 9 years), and control group
      consisted of 28 healthy children (14 males and 14 females, age range 3 - 12
      years, mean 7 years) were treated and run through the flow cytometry. The data
      were obtained by using Simultest IMK-Lymphocyte software and the percentage of
      CD(3)(+), CD(3)(+)CD(4)(+), CD(3)(+)CD(8)(+), CD(3)(-)CD(19)(+) and CD(3)(-)CD(16
      + 56)(+) cells were counted. The percentage of T(H1) and T(H2) cells were gained
      through determination of intracellular cytokines IFN-gamma or IL-4 in CD(4)(+)
      cells by flow cytometry. The 35 patients with MP were hospitalized at our
      hospital. In addition to fever and cough, all the patents had abnormal X-ray
      findings and/or moist rale on auscultation of the lungs. The IgM antibody to
      Mycoplasma pneumoniae was positive in each patient. Immunoglobulins were
      measured, and PPD skin tests were performed in 30 out of the 35 patients with MP.
      T test and rank sum test by SPSS FOR WINDOWS 10.0 was used for statistical
      analysis. RESULTS: The percentage of CD(3)(+) and CD(4)(+) T lymphocyte was 68.00
      +/- 6.66 and 37.86 +/- 5.84, respectively, in MP group, and 63.71 +/- 7.92 and
      34.54 +/- 6.23 in control group (P < 0.05). The percentage of T(H1) cells was
      14.13 +/- 8.46 in patients and 20.77 +/- 6.89 in normal control group (P =
      0.001). The percentage of NK cells was 15.57 +/- 12.16 and 20.39 +/- 9.64 in MP
      and control group (P < 0.01). The ratio of T(H1)/T(H2) in MP group was lower than
      that in control group (P < 0.05). However the percentage of CD(8), T(H2), B cells
      and CD(4)/CD(8) had no difference between the MP and control groups. The levels
      of IgG, IgA, and IgM in serum were normal in most of patients except for a few
      patients who had elevated IgA and IgM levels. The PPD skin tests were negative in
      30 out of 35 patients. CONCLUSION: In this study a higher percentage of CD(3)(+),
      CD(4)(+) T lymphocyte and lower percentage of T(H1), NK cells in PBMC of patients
      with mycoplasma pneumonia were found. The ratio of T(H1) and T(H2) cells in
      patients was also lower. None of thirty patients had positive PPD skin tests.
      Unbalanced cell-mediated immunity with a tendency toward T(H2) existed in
      patients with MP. Therefore, immunomodulators may be useful in treatment of
      mycoplasma pneumonia.

PMID- 14733804
TI  - [Hematuria occurred after inoculation of DPT combined vaccine in a child].

PMID- 14733803
TI  - [Eosinophils apoptosis, fas mRNA and bcl-2 mRNA expressions in asthma model of
      young rat and effects of achyranthes bidentata polysaccharides].
AB  - OBJECTIVE: Asthma is a chronic respiratory tract disorder characterized by airway
      hyperreaction (AHR), persistent airway inflammation, high serum IgE,
      overproduction of IL-4, IL-5 and IL-13 by allergen-specific Th2 cells. The
      morbidity and mortality of asthma have continued to increase despite the use of
      currently available therapeutic agents. The reputed effects of traditional
      Chinese medicines (TCMs) have led to increasing use of TCMs for treatment of
      asthma throughout the world. The aims of this study were to investigate in asthma
      model of young rat the mRNA expressions of apoptotic gene fas and bcl-2,
      eosinophils (EOS) apoptosis in airway, and effects of achyranthes bidentata
      polysaccharides (ABPS), a group of polysaccharides extracted from TCM Achyranthes
      bidentata blume, on treatment of asthma. METHODS: Fifty Sprague-Dawley (SD) rats
      were divided into five groups, 10 rats per group. Asthma in rats was induced by
      intraperitioneal sensitization and challenge with nebulized ovalbumin (OVA). A
      pretreatment with ABPS [50 mg/(kg x d)] was done according to three different
      schedules: consecutively 3 days at sensitization (T1), at challenge (T2) or both
      of the two periods (T3). Sham-treated rats (A) and naive rats (C) served as
      controls. The animals were sacrificed 24 hours after the last challenge. The mRNA
      expression of bcl-2 and fas in eosinophils presenting in airway and the apoptosis
      of eosinophils in airway were assessed by using in situ hybridization with
      oligonucleotide probe and TUNEL methods, respectively. RESULTS: (1) Twenty-four
      hours after the last antigen challenge, the mRNA expression of fas in eosinophils
      presenting in airway significantly decreased in group A [(43.4 +/- 10.0)%]
      compared with that in group C [(73.2 +/- 11.9)%] (P < 0.01). ABPS could increase
      the fas mRNA expression significantly in all the three groups [(59.0 +/- 8.1)%,
      (57.5 +/- 9.6)%, (76.2 +/- 2.7)%], compared with that in group A (P < 0.05, P <
      0.05, P < 0.01, respectively). The expression of the bcl-2 mRNA in group C was
      (47.9 +/- 8.7)%, it was elevated to (67.4 +/- 7.3)% in group A (P < 0.01). The
      expression of the bcl-2 mRNA in ABPS treated T1 and T3 groups was significantly
      lowered [(57.7 +/- 12.7)%, (57.3 +/- 6.8)%, P < 0.05], but not in T2 group [(72.4
      +/- 6.7)%]. (2) In group A, the EOS presenting in the airway increased
      significantly, but there were few apoptotic EOS; the percentage of apoptotic
      eosinophil was distinctly lower in group A than that in group C [(5.3 +/- 2.2)%
      vs. (15.9 +/- 2.4)%, P < 0.01]. Compared with that in group A, the eosinophil
      apoptosis ratio in those ABPS treated groups T1, T3 was evidently elevated [(8.7
      +/- 2.9)%, (9.8 +/- 2.2)%, P < 0.05, P < 0.05], but ABPS treated at challenge
      (T2) could not change the eosinophil apoptosis ratio significantly (P > 0.05).
      CONCLUSION: (1) In asthmatic rat, the expressions of the genes fas and bcl-2 mRNA
      in EOS were changed evidently and the ratio of EOS apoptotosis reduced greatly.
      (2) ABPS could enhance the apoptosis of EOS by upregulating the expression of the
      genes fas and bcl-2 mRNA.

PMID- 14733805
TI  - [Analysis on association of glucocorticoid receptor gene polymorphism with
      steroid-resistance in idiopathic nephrotic syndrome of children].
AB  - OBJECTIVE: The nephrotic syndrome is defined by heavy proteinuria, edema,
      hypoalbuminemia, and hyperlipidemia. Idiopathic nephrotic syndrome (INS) mainly
      occurs in children, which is generally treated with glucocorticoids. The majority
      of patients are steroid-sensitive (SSINS) while steroid-resistance occurs in a
      subset of NS children (SRINS). Although intensive efforts have been undertaken to
      study the associations between SRINS and renal pathological changes,
      pharmacokinetics, and the GR density and binding affinity, the mechanisms
      underlying steroid-resistance are still not elucidated entirely. The authors
      hypothesized that it might be associated with polymorphisms in the glucocorticoid
      receptor gene (NR3C1). The study aimed to screen the NR3C1 gene for polymorphisms
      in genomic DNA samples from SRINS, SSINS children and control group, and to
      analyze the association of the polymorphisms in the NR3C1 gene and SRINS of
      children. METHODS: Totally 39 SRINS and 67 SSINS children (81 males and 25
      females with the mean age of 7 years) were involved in the study. Umbilical cord
      blood of 62 normal neonates and peripheral blood of 2 healthy volunteers were
      selected as controls. Genomic DNA was isolated from peripheral blood lymphocytes
      of all subjects. All the NR3C1-coding exons and intron-flanking portions were
      amplified by polymerase chain reaction (PCR). For polymorphism screen, PCR
      products were analyzed by denaturing high performance liquid chromatography
      (DHPLC). DNA fragments with aberrant elution profiles were re-amplified and
      sequenced directly. RESULTS: Twelve aberrant elution profiles were identified
      with DHPLC in SRINS, SSINS and controls. Among them, 6 previously reported
      polymorphisms and 6 novel polymorphisms were confirmed by sequencing (198G > A,
      200G > A, IVSD-16G > T, 1896C > T, 2166C > T, 2430T > C; novel, 1206C > T, 1374A
      > G, IVSG-68_IVSG-63delAAAAAA, 2193T > G, IVSH-9C > G, 2382C > T), and 3 groups
      of SNPs were in complete linkage disequilibrium, which resulted in 3 different
      haplotypes ([198G > A + 200G > A], [1374A > G + IVSG-68_IVSG-63delAAAAAA + IVSH
      9C > G + 2382C > T], [1896C > T + 2166C > T + 2430T > C]). The last two genotypes
      were first reported. The genotype frequencies of the 2 novel haplotypes were
      10.3% vs 1.5% in SRINS and SSINS, and 15.4% vs 7.5% in SRINS and SSINS,
      respectively. Other polymorphisms were relatively rare detectable both in
      patients and controls. CONCLUSION: Twelve polymorphisms in the NR3C1 gene were
      detected with the technique of DHPLC, of which six polymorphisms were identified
      at the first time. Two types of newly found haplotypes were associated with
      steroid-resistant idiopathic nephrotic syndrome of children, which might be
      responsible for steroid-resistance in partial idiopathic nephrotic syndrome of
      children.

PMID- 14733806
TI  - [Effect of hepatitis B vaccine immunization on HBV associated nephritis in
      children].
AB  - OBJECTIVE: Hepatitis B has been extensively prevalent in China and hepatitis B
      virus associated nephritis (HBV-GN) has been one of the common renal damages
      secondary to HBV infection in Chinese children. Regular vaccination against
      hepatitis B has been carried out nation-wide in China since January 1st, 1992.
      The present study was conducted to evaluate the effect of regular vaccination
      against hepatitis B virus on the incidence of childhood HBV-GN and membranous
      nephropathy (MN). METHODS: Retrospective analysis on the results of renal biopsy
      in 727 patients (from Nov. 1979 to March 2002) was carried out. The patients were
      first divided into two groups according to the date when the patients were seen.
      Group A patients were seen from Nov. 1979 through Dec. 1991; Group B patients
      were seen from Jan. 1992 through March 2002. Group B patients were further
      divided into 5 subgroups (Group B(1) to B(5)), with a 2-year interval after 1992.
      Secondly, each of these groups and subgroups were again divided into two groups,
      vaccinated and unvaccinated groups. RESULTS: In 727 renal biopsies, 64 cases
      (8.80%) met HBV-GN diagnostic criteria. Twenty-eight cases were diagnosed as HBV
      GN in Group A (211 cases), accounting for 13.27%, while there were 36 cases with
      HBV-GN in 516 renal biopsies of Group B, accounting for 6.98% (chi(2) = 7.397 and
      P < 0.01). The frequency in Group B was significantly lower. Prevalence rate
      (from Group A to Group B(5)) was 13.3% (28/211), 13.0% (9/69), 7.3% (6/82), 6.3%
      (4/64), 4.9% (4/82), 5.9% (13/219), respectively, which showed a tendency of
      decline. Only 8 cases of HBV-GN occurred in vaccinated group (231 cases),
      accounting for 3.5%, while 48 cases of HBV-GN were seen in unvaccinated group
      (381 cases), accounting for 12.6% (chi(2) = 14.44 and P < 0.001), vaccination
      history was unknown in 115 of the 727 cases. In 727 renal biopsies, pathological
      type of 46 cases (6.3%) was membranous nephropathy and all of them had HBV-GN.
      Six cases of MN occurred in vaccinated group, accounting for 2.60%, while 40
      cases with membranous nephropathy were found in unvaccinated group, accounting
      for 10.5% (chi(2) = 12.92 and P < 0.001). On the other hand, in vaccinated group
      there still were 8 cases of HBV-GN whose serum markers of HBV were positive. Two
      of their mothers had apparent evidence of hepatitis B virus infection.
      CONCLUSION: The frequency of HBV-GN has decreased significantly after vaccination
      against hepatitis B virus was routinely carried out since 1992; at the same time,
      childhood membranous nephropathy might be decreasing gradually, too. The cause of
      individual cases of HBV-GN who has be vaccinated was probably due to maternal
      infant transmission and immunization failure. Attention should be paid to
      interruption of maternal-infant transmission and serological follow-up should be
      performed in high-risk newborns after vaccination to further lower the incidence
      of hepatitis B virus associated nephritis.

PMID- 14733807
TI  - [A child with cerebral malaria complicated with cranial nerve injury].

PMID- 14733809
TI  - [Drash syndrome in a case].

PMID- 14733808
TI  - [CYP21 gene point mutations study in 21-hydroxylase deficiency patients].
AB  - OBJECTIVE: The major cause of congenital adrenal hyperplasia (CAH) is 21
      hydroxylase deficiency, which accounts for 90% - 95% of all cases in most
      populations. This study was conducted to characterize the molecular basis of the
      21-hydroxylase deficiency and to obtain the spectrum of the CYP21 gene mutations
      in a group of Chinese patients, and analyze the relationship of genotype and
      phenotype. METHODS: To detect the distribution of gene mutations in Chinese
      population samples from 52 patients with 21-hydroxylase deficiency from 51
      families were collected, including two parents samples in 30 patients and one
      parents sample in 10 patients. Blood samples were obtained for extraction of
      peripheral blood lymphocytes. Polymerase chain reaction (PCR) followed by nesed
      PCR were used to study the 21-hydroxylase gene (CYP21) mutations. The primary PCR
      amplified two overlapping CYP21-specific DNA fragments, The product of the nested
      PCR which used products from the primary PCR was analysed by restriction fragment
      length polymorphism (RFLP) or amplification-created restriction site (ACRS). All
      patients were studied by 6 mutations, including P30L, I2g (intron 2 nt 656 c/a-
      >g splice mutation), E3Delta8nt (exon 3 codon111-codon113 8 bp deletion), I172N,
      V281L and Q318X. RESULTS: Through analysis of 52 patients with 21-hydroxylase
      deficiency, in 5 patients no mutations were detected, in 17 patients only one
      mutated allele could be characterized, two different mutations were identified in
      21 patients, three mutations were detected in 2 patients. Totally, in 73% of
      alleles the genotypes could be detected. The most common mutation was I2g, which
      present on 31% affected alleles, then followed by I172N, Q318X, V281L, P30L,
      E3Delta8nt, accounting for 23%, 14%, 9%, 3%, 2% of all identified mutations
      respectively, which included multiple mutations accounting for 6%. The most
      frequent molecular defects of the salt-wasting form were the I2g (45.7%), Q318X
      (26%). Of the simple virilizing form, the dominant mutations were I172N (40.7%)
      and I2g (18.5%). CONCLUSION: Six different mutations were examined in this study,
      and the detected mutations accounted for 73% affected alleles, in which I2g and
      I172N were the most common mutations (accounting for 54%). Correlation between
      genotypes and phenotypes was compatible with the reported data. Two rounds of PCR
      followed by RFLP or ACRS analysis may provide important information for genetic
      counseling and for prenatal diagnosis.

PMID- 14733810
TI  - [Analysis of haplotype-based haplotype relative risk and transmission
      disequilibrium test in childhood absence epilepsy].
AB  - OBJECTIVE: Childhood absence epilepsy (CAE), a common form of idiopathic
      generalized epilepsy, accounts for 8% - 15% of all childhood epilepsies. A
      positive family history of epilepsy, a hereditary factor being one of the
      pathogeneses, is found in 15% - 44% of children with absence seizures. The
      phenotype of CAE is specific (including seizure forms and EEG), therefore it is
      suitable for genetic study. The purpose of this study was to confirm the linkage
      of childhood absence epilepsy to chromosome 8q24 in China. METHODS: Twenty-nine
      trios families (a patient and his/her parents) as patient group and 10 normal
      trios families as control group were investigated for chromosome 8q24 by
      haplotype analysis with 5 microsatellite DNA markers (D8S554, D8S534, D8S1100,
      D8S1783, D8S1753). Genomic DNA was isolated from 4 ml human peripheral blood by
      using the conventional procedure, and then was treated using the PCR method. PCR
      products were analyzed by gene scan. Statistical methodology included haplotype
      based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT).
      RESULTS: In this study, the polymorphism information content (PIC) of 5
      microsatellite DNA markers were: 0.519, 0.828, 0.528, 0.654 and 0.772. HHRR
      showed D8S554(4) (chi(2) = 5.939, P < 0.05), D8S1100(3) (chi(2) = 5.081, P <
      0.05), D8S1783(6) (chi(2) = 4.308, P < 0.05). TDT showed D8S554(4) (chi(2) =
      4.46, P < 0.05), D8S1783(6) (chi(2) = 4, P < 0.05). In order to exclude false
      association results, the authors analyzed every family in detail. Four trios
      families transmitted allele D8S1783(6) to their offspring, and the same allele
      hasn't been found in controls. The further work showed that locus D8S1783 had
      transmission disequilibrium with CAE, the other two loci were a false
      association. CONCLUSION: (1) Childhood absence epilepsy in the Chinese population
      may be linked to chromosome 8q24, the CAE gene is transmitted disequilibrium on
      locus D8S1783. Combined with other research results, we suppose that CAE gene may
      be in the ECA1 area on chromosome 8q24. (2) The CAE gene perhaps has a genetic
      heterogeneity in the population of different areas and different races. (3) HHRR
      and TDT seem to be the best statistical methods to do linkage disequilibrium
      study in the trios family.

PMID- 14733812
TI  - [Experimental study on the therapeutic mechanism of high dose intravenous
      immunoglobulin in treatment of immune-mediated peripheral neuropathy].
AB  - OBJECTIVE: To explore the therapeutic basis of high dose intravenous
      immunoglobulin (IVIg) in treatment of peripheral neuropathy induced by
      Campylobacter jejuni lipopolysaccharide (CJ LPS). METHOD: (1) IVIg (400 mg/kg x
      d) was given to the rats on the different days respectively during the
      immunization with CJ LPS. Histological study of sciatic nerve was performed on
      the 35 th day after immunization. The titer of anti-CJ LPS antibody in sera of
      immunized rats was measured by ELISA; IgG deposition was detected by
      immunohistochemistry and expression of TNF-alpha mRNA in the pathological nerves
      by in situ hybridization histochemistry. (2) When PBMCs were stimulated by CJ LPS
      in vitro, IVIg was added into culture medium at the doses of 1, 2.5, 5, and 10
      mg/ml, respectively. Pathological examination of sciatic nerve was performed on
      the 7th day after perineural injection of the supernatants. Expression of TNF
      alpha mRNA in PBMCs stimulated by CJ LPS in medium was detected by in situ
      hybridization histochemistry after adding IVIg. RESULTS: (1) The rate of abnormal
      fibers appearance in IVIg group (1.0%) was much lower than that of the control
      group (15.0%) after immunization with CJ LPS, P < 0.01. The titer of antibody in
      control group was 9 times higher than that of IVIg group. There was no expression
      of immunoglobulin and TNF-alphamRNA in peripheral nerves in IVIg group, but high
      expression was found in control group in which no IVIg was injected. (2) The
      expression rates of TNF-alphamRNA on the PBMCs in IVIg group (1.0%) was much
      lower than that of control group (9.5%). (3) When the PBMCs of normal rats were
      stimulated by CJ LPS, the expression rates of TNF-alphamRNA in PBMCs of 5 mg/ml
      IVIg group (3.0%) or 10 mg/ml IVIg group (2.0%) were much lower than that of 1
      mg/ml IVIg group (15.0%) or 2.5 mg/ml IVIg group (11.5%), P < 0.01. The rate of
      abnormal fibers appearance in 5 mg/ml IVIg group (9.8%) or 10 mg/ml IVIg group
      (8.5%) was much lower than that of 1 mg/ml IVIg group (50.0%), 2.5 mg/ml IVIg
      group (41.0%) or control group (50.8%) after the perineural injection with the
      supernatants, respectively, P < 0.01. CONCLUSION: The therapeutic effect of high
      dose IVIg might be associated with inhibition of the humoral and cellular
      immunity simultaneously in peripheral neuropathy induced by CJ LPS.

PMID- 14733811
TI  - [Clinical characteristics of alternating hemiplegia of childhood in 13 patients].
AB  - OBJECTIVE: To summarize the clinical characteristics of alternating hemiplegia of
      childhood (AHC). METHODS: The clinical data of 13 children with AHC were
      analyzed. Cranial MRI, EEG, analysis of serum amino acids and urinary organic
      acids, measurement of plasma lactate and pyruvate levels were done in all
      patients. Other laboratory examinations such as magnetic resonance angio-imaging
      (MRA), digital subtraction arteriography (DSA) and Video-EEG were also performed
      in some patients. RESULTS: Of the 13 patients, 12 were male, and 1 was female.
      The age of onset was from 2 days to 55 months (average 13.1 months). The initial
      symptoms were abnormal ocular movements (AOMs) consisting of ocular deviation,
      gaze or nystagmus in 2 cases, AOMs and dystonic posturing in 9 cases, hemiplegia
      in 2 cases. All patients had recurrent alternating hemiplegic episodes. The
      hemiplegic attacks lasted from a few minutes to 10 days. The occurrence of the
      attacks ranged from 8 times daily to one time every 2 months. In 10 patients the
      abnormal eye movements or dystonic posturing, at times, recurred intermittently
      during the hemiplegic attack. Choreoathetosis was present in 2 cases. Ataxia was
      present in 1 case; 7 patients also had the episodes of quadriplegia. During the
      episodes of quadriplegia, dysarthria or aphasia was present in 4 cases, dyspnea
      and dysphagia was present in 2 cases, respectively. Sleep could relieve both
      weakness and associated paroxysmal symptoms. Mental retardation was present in 9
      cases, seizures in 3 cases. Except for EEG or Video-EEG was abnormal in 3
      patients, other laboratory investigations were normal in all patients. Twelve
      patients received flunarizine therapy. Flunarizine reduced the severity,
      duration, or frequency of hemiplegic attacks in 8 patients. CONCLUSION: The
      results suggest that AHC is characterized by frequent episodes of alternating
      hemiplegia with extrapyramidal symptoms and mental retardation, flunarizine is
      effective in treating some AHC patients.

PMID- 14733813
TI  - [Analysis of antimicrobial resistance of Streptococcus pneumoniae with
      restriction fragment length polymorphism of pbp2b gene and pulsed-field gel
      electrophoresis profiles among children].
AB  - Streptococcus pneumoniae is a common cause of potentially life-threatening
      infections such as meningitis, bacteraemia, pneumonia worldwide, for which
      children of preschool age are at particularly high risk. Since the late 1970s and
      1980s, antibiotic resistance among pneumococci has become an emerging problem.
      Several multidrug-resistant clones have rapidly spread throughout the world.
      OBJECTIVE: (1) To investigate the prevalence of penicillin and other antibiotics
      nonsusceptibility among pneumococci. (2) To analyze the correlation of pbp2b
      amplicon profiles with penicillin resistance. (3) To serotype 31 isolates of
      penicillin-resistant pneumococci by latex agglutination. (4) To analyze the
      chromosomal relatedness of serotype 23F and 6 isolates of penicillin-resistant
      pneumococci by using pulsed-field gel electrophoresis (PFGE) and characterize
      these isolates in molecular epidemiology. METHODS: (1) Susceptibility was
      determined by using broth microdilution, E-test, and K-B disk. (2) The
      correlation of pbp2b amplicon profiles with penicillin resistance was assessed by
      restriction fragment length polymorphism (RFLP). (3) Serotyping of penicillin
      resistant pneumococcal isolates was performed by using latex agglutination. (4)
      The properties of serotype 23F and 6 isolates of penicillin-resistant pneumococci
      were assessed by PFGE. RESULTS: S. pneumoniae with increased nonsusceptibility
      (including intermediate strains and resistant strains) to penicillin G was 9.9%
      in 1997, 12.6% in 1998, 14.6% in 2000; to cefuroxime 4.2%, 1.5%, 8.2%; to
      cefotaxime 0.0%, 1.7%, 1.0% respectively. There were no statistically significant
      differences (P > 0.05). While resistance to erythromycin, trimethoprim
      sulfamethoxazole and chloramphenicol increased significantly from 76.8% in 1997
      to 87.4% in 2000, from 74.7% to 88.3%, and from 22.6% to 40.8%, respectively (P <
      0.05). RFLP analysis of pneumococcal pbp2b-specific amplicons was effective for
      screening penicillin resistance. Of the 31 strains of penicillin-resistant
      pneumococci (MICs 0.12 - 2.0 micro g/ml) studied, 6 (19.4%) strains (MICs 0.12 -
      0.19 micro g/ml) were serotype 23F and 3 (9.7%) strains (MICs 0.5 - 1.5 micro
      g/ml) were serotype 6. There were nearly identical susceptibility to antibiotics
      and identical PFGE patterns in the former, and there were different
      susceptibility to antibiotics and different PFGE patterns in the latter. Three
      serotype 6 strains had different susceptibility to antibiotics and different PFGE
      patterns, which suggested that those strains may be scattered. CONCLUSION:
      Generally beta-lactams retained their activity against S. pneumoniae in Beijing.
      Resistance to erythromycin, trimethoprim-sulfamethoxazole, and chloramphenicol
      increased drastically. RFLP analysis of pneumococcal pbp2b-specific amplicons was
      effective for screening penicillin resistance. In 6 strains of serotype 23 F
      there were nearly identical susceptibility to antibiotics and identical PFGE
      patterns, which suggested the probability that there was a spread of serotype 23F
      isolates with low-level penicillin resistance in local area.

PMID- 14733814
TI  - [Molecular diagnosis of the specific DNA patterns of 16S-23S rRNA gene of
      bacteria].
AB  - OBJECTIVE: To establish the specific 16S-23S rRNA gene spacer regions pattern in
      different bacteria using polymerase chain reaction (PCR), restriction fragment
      length polymorphism (RFLP), DNA cloning and sequences analysis. METHODS: A pair
      of primers were selected from highly conserved sequences adjacent to the 16S-23S
      rRNA spacer region. Bacterial DNA of sixty-one strains of standard bacteria and
      corresponding clinical isolates representative of 20 genera and 27 species was
      amplified by PCR, and further studied by RFLP, DNA cloning and sequences
      analysis. Meanwhile, all specimens were examined by bacterial culturing and PCR
      RFLP analysis. RESULTS: The 27 different standard strains showed one, two, three
      or more than three bands. The sensitivity of PCR reached 2.5 colony-forming unit
      (CFU), and there was no cross reaction to the human, fungal or viral genomic
      DNAs. Fifteen species could be distinguished immediately by PCR, while another 10
      species were further identified by Hinf I or Alu I digestion. Klebsiella
      pneumoniae (Kp) and Enterococcus durans (Ed) could not be differentiated from
      each other by Alu I or Hinf I digestion. The spacer sequences of the Kp and Ed
      were 908 bp and 909 bp, respectively, and they differed only at the site of the
      779th nucleotide. The former was G, and the latter was A. The 760 - 790 bp
      sequence of Kp was as follows: CGACTGCACCGCCTCCTAC / GGCCGCGTATTC. The 760 - 790
      bp sequence of Ed was as follows: CGACTGCAC CGCCTCCTAC / AGCCGCGTATTC. Only one
      enzyme XmaIII, could discriminate the two. The cleaving site of XmaIII is C
      downward arrow GGCCG. Kp DNA was cleaved into 778 bp and 130 bp fragments, while
      E. durans was not. Of 42 specimens with suspected septicemia, 15 were positive
      (35.7%) on blood culture, and 27 on PCR (64.29%). The positive rate of PCR was
      significantly higher than that of blood culture (P < 0.01). Of the six CSF
      specimens, one was positive for Staphylococcus epidermidis (Se) on culture as
      well as by PCR, while two specimens which were negative on cultures were positive
      by PCR and were diagnosed as Se according to its DNA pattern. One specimen was
      culture-positive for Cryptococcus neoformans (Cn) but was negative by PCR. The
      other two specimens were negative by both PCR and culture. Fifteen blood samples
      from healthy children were negative by both blood culture and PCR. CONCLUSIONS:
      The method of detecting bacterial 16S-23S rRNA spacer regions using PCR-RFLP
      techniques was specific, sensitive, rapid and accurate in detecting pathogens in
      clinical bacterial infections.

PMID- 14733815
TI  - [Jeune syndrome in a case].

PMID- 14733816
TI  - [Validation study on the criteria for clinical classification of small for
      gestational age infants].
AB  - OBJECTIVE: To study the validity of criteria currently used in China for the
      classification of symmetric small for gestational age infants (SGA) as compared
      with its definition. METHODS: This study included 417 inpatients diagnosed as SGA
      in authors' hospital from January 1998 to June 2002. Symmetric SGA was diagnosed
      by the following three criteria: (1) the Ponderal Index (PI), (2) the crown-heel
      length-to-head circumference ratio (BL/HC) issued in Chin J Pediatr (1988;26:164 
      165), as well as (3) the SGA definition. The definition criterion was considered
      as the "gold standard". The sensitivity, specificity, false positive and negative
      values, positive and negative predictive values, exact agreement ratio, diagnosis
      index, and Cohen's Kappa value were used to evaluate the validity and agreement
      of the methods of PI and BL/HC. Receiver Operating Characteristic (ROC) analysis
      was used to evaluate the validity of the diagnosis. RESULTS: Of 417 SGA infants,
      376 (90.17%), 376 (90.17%) and 187 (44.84%) subjects were diagnosed as symmetric
      type with PI, BL/HC and the definition criteria, respectively. (2) The agreement
      rate and Kappa value between PI and BL/HC was 80.82% and -0.093 (SEM 0.026),
      respectively. And the agreement rates between PI or BL/HC and the definition
      criterion were 49.88% and 50.84%, respectively. As compared with the definition
      criterion, the PI and BL/HC methods had sensitivities of 91.8% - 96.4%,
      specificities of 9.3% - 25.9%, positive predictive values of 45.8% - 51.1%,
      negative predictive values of 72.7% - 82.8%, diagnosis indices of 4.9% - 17.7%
      and Kappa values of 0.070 - 0.167. (3) The areas under the ROC curves in full
      term and preterm infants by PI method were 0.635 (95% CI, 0.573 - 0.697) and
      0.698 (95% CI, 0.622 - 0.725), respectively. PI cutoffs at 2.47 in full-term SGA,
      at 2.43 in preterm SGA, and BL/HC cutoff at 1.43 produced the maximum diagnosis
      indices that were 24.7%, 39.6% and 33.7%, respectively. When the PI at 2.50 (full
      term), PI at 2.31 (preterm) and BL/HC values at 1.46, the sensitivity closed
      mostly to the specificity. The sensitivities and specificities in full-term and
      preterm infants were 59.4% and 59.3%, 65.3% and 65.5%, and 66.3% and 65.5%,
      respectively. CONCLUSION: In the classification of SGA, the results showed a poor
      agreement between PI or BL/HC and the definition criterion. The results suggested
      that the current cutoffs of PI and BL/HC might not be appropriate for the
      diagnosis of symmetric SGA. Low AUC suggested that PI and BL/HC could not give a
      valid diagnosis at any cutoffs.

PMID- 14733817
TI  - [Clinical analysis of 126 children with hemorrhagic fever with renal syndrome].

PMID- 14733818
TI  - [Analysis of early immune reconstitution following cord blood transplantation
      from siblings in two patients by flow cytometry].

PMID- 14733819
TI  - [One case of Sturge-Weber syndrome].

PMID- 14733820
TI  - [Idiopathic interstitial pneumonitis in child].

PMID- 14733821
TI  - [A child with chronic inflammatory demyelinating polyneuropathy (CIDP)].

PMID- 14733823
TI  - [Explanation of differences between GINA 2002 and GINA 1995 in asthma definition,
      diagnosis and management].

PMID- 14733824
TI  - [Penicillin skin test: status quo].

PMID- 14733825
TI  - [Pseudohypoparathyroidism mis-diagnosed as epilepsy in a case].

PMID- 14733826
TI  - [Two special cerebral hyponatremia].

PMID- 14733827
TI  - [A brief introduction to the international scientific symposium on early brain
      development of children].

PMID- 14733828
TI  - [A case of succinic semialdehyde dehydrogenase deficiency].

PMID- 14733829
TI  - Kidney cancer management in 2004: an update for the practicing general urologist.

PMID- 14733830
TI  - Heat shock-peptide complex vaccine as adjuvant therapy for high-risk patients
      with resected renal cell carcinoma.

PMID- 14733831
TI  - Update on minimally invasive approaches to kidney tumors.
AB  - Renal tumors are being detected at increasing rates because of widespread use of
      modern imaging techniques such as ultrasonography and computed tomography.
      Typically, these tumors, many of which are discovered incidentally, tend to be
      small and are confined to the kidney. Advances in ablative and imaging technology
      have led to the application of minimally invasive therapy in the treatment of
      small renal tumors. Although still evolving as a cancer treatment, minimally
      invasive treatment potentially offers several advantages over conventional open
      renal surgery: shorter convalescence, improved cosmesis, reduced postoperative
      pain, and renal preservation. This article reviews the status and recent progress
      of minimally invasive approaches to renal neoplasm.

PMID- 14733832
TI  - A medical oncologist's approach to immunotherapy for advanced renal tumors: is
      nephrectomy indicated?
AB  - Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although
      interleukin-2 and interferon remain the most active agents for this disease, long
      term survival rates remain poor. Two phase 3 trials, European Organization
      Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have
      demonstrated a survival benefit of nephrectomy followed by interferon versus
      interferon alone in patients having an excellent performance status (PS 0 and 1).
      Removal of the primary tumor followed by interferon is not recommended for
      patients with a moderate or poor PS (PS 2-4). Even with this aggressive approach,
      most patients eventually will die from their kidney cancer; therefore, every
      patient with metastatic disease should be considered for enrollment into clinical
      trials.

PMID- 14733833
TI  - The role of lymphadenectomy in renal cell carcinoma.
AB  - The standard of care for localized and metastatic renal cell carcinoma includes a
      nephrectomy. The potential benefits for lymphadenectomy include more accurate
      staging, decreased risk of local recurrence, and improved survival. However, the
      benefits of lymph node dissection have not been proven.

PMID- 14733834
TI  - Applications of positron emission tomography imaging, intraoperative
      ultrasonography, magnetic resonance imaging, and angiography in the evaluation of
      renal masses.
AB  - Most renal masses and cysts are adequately characterized by ultrasonography or
      computerized tomography. Occasionally, further diagnostic evaluation is needed.
      Magnetic resonance imaging has emerged as the premier study to evaluate suspected
      tumor thrombus and to plan the operative technique in challenging cases.
      Intraoperative ultrasonography is a valuable real-time imaging modality for
      delineating tumor extent and margins during nephron-sparing surgery and in
      evaluating the presence of synchronous multifocality. Additionally, localized
      central renal tumors can be treated with ultrasonography-guided radiofrequency
      ablation. Positron emission tomography has little use in the diagnostic
      evaluation of renal masses, but may be useful in staging equivocal cases and in
      evaluating suspected recurrence or metastases in patients after nephrectomy for
      renal cell carcinoma.

PMID- 14733836
TI  - Radiofrequency ablation of renal tumors.
AB  - Radiofrequency ablation (RFA) of renal tumors is a relatively new treatment
      modality in the armamentarium of urologic surgeons. One of the challenges of this
      technique is attaining a zone of tissue destruction sufficient enough to kill the
      targeted tumor. Technologic innovations have aided in this effort. The clinical
      experience with RFA of renal tumors suggests that small, exophytic tumors may be
      more readily ablated. Although there is much optimism with regard to this
      technology, further study is required to better define the oncologic efficacy and
      refine proper patient selection.

PMID- 14733837
TI  - Molecular profiling of prostate cancer.
AB  - The ability to distinguish between aggressive and nonaggressive tumors has not
      changed despite vast improvements in the detection of prostate cancer (PCA). To
      improve predictive accuracy, additional PCA-specific biomarkers must be
      identified and it is the emerging microarray technology and gene expression
      profiling that appear to be capable of achieving this goal. Through comparisons
      of a number of published microarray studies of PCA, several potential biomarkers
      appear on the horizon, including the serine protease Hepsin, a-methylacyl CoA
      racemase, and the human homologue of the Drosophila protein Enhancer of Zeste.
      Although these markers will move toward validation by eventual protein expression
      studies, another aspect of microarray expression, global signature expression
      patterns through multidimensional scaling, appears to be promising in
      distinguishing between aggressive and nonaggressive forms of PCA or in
      distinguishing PCA from benign prostatic hyperplasia or normal prostate tissue.

PMID- 14733838
TI  - Gene therapy treatments for erectile and bladder dysfunction.
AB  - The postgenomic age presents many exciting challenges and opportunities for the
      application of molecular medicine to the treatment of lower urinary tract
      diseases. Chief among these are the therapeutic possibilities afforded to
      selectively modulate/alter gene expression in somatic cells to "normalize"
      aberrant cellular responses to the existing hormonal milieu. In this paper, this
      therapeutic strategy will be referred to as gene therapy or gene transfer. This
      article specifically reviews the potential use of gene therapy/transfer to the
      treatment of bladder and erectile dysfunction. Available treatments for both of
      these common urologic diseases/disorders have contraindications, untoward side
      effects, or limited efficacy in certain patient populations. Moreover, that
      genetic material can be locally administered in the bladder and penis removes a
      major therapeutic obstacle to the use of gene transfer. Thus far, "proof-of
      concept" has been demonstrated in preclinical studies using cellular and
      molecular strategies on a variety of gene targets. The continuing evolution of
      gene transfer vectors and gene delivery technologies is expected to further
      enhance the selectivity, efficacy, and duration of gene therapy, making it a
      viable treatment option for the amelioration of lower urinary tract
      diseases/disorders.

PMID- 14733841
TI  - Treatment of adrenocortical carcinoma: contemporary outcomes.
AB  - Adrenocortical carcinoma is a rare cancer that historically has been associated
      with poor outcome. Throughout the past decades, growing experience has allowed
      better understanding of the natural history and optimal management of this
      cancer. Advances in imaging and aggressive surgical therapy have raised the
      outlook for recently diagnosed patients. Further improvements in survival will
      require more effective systemic therapy.

PMID- 14733842
TI  - Evaluation of the incidentally discovered adrenal mass.
AB  - The increased use of abdominal ultrasonography, computed tomography, and magnetic
      resonance imaging has led to the classification of adrenal lesions termed the
      incidentally identified adrenal mass or adrenal incidentaloma. Unlike for the
      large, clinically, or biochemically symptomatic adrenal mass, the evaluation of
      patients with small, asymptomatic, or nonfunctional adrenal lesions remains
      controversial. The evaluation of these adrenal incidentalomas presents a
      challenge to endocrinologists, radiologists, and urologic surgeons alike. A
      multidisciplinary approach with biochemical screening and radiologic evaluation
      is essential to assess the nature and function of these lesions. Furthermore, it
      is of great importance to identify patients who are morbidly affected by hormonal
      hypersecretion or malignant potential. This article describes the emerging
      guidelines for the evaluation of the incidental adrenal mass.

PMID- 14733843
TI  - What Is the Clinical Impact of Macrolide Resistance?
AB  - Respiratory tract infections are treated empirically. Treatment is based on the
      likely pathogens and their antibiotic susceptibility. The most common respiratory
      tract pathogen is Streptococcus pneumoniae. In the United States, approximately
      25% to 30% of S. pneumoniae are resistant to erythromycin and other macrolides.
      There are two mechanisms of resistance: ribosomal methylation that causes high
      level resistance, and an efflux pump that causes low-level resistance. Macrolides
      are ineffective in animal models that use pneumococcal isolates with the
      methylase- or efflux-mediated resistance mechanisms. There are many case reports
      that describe clinical failure and isolation of a macrolide-resistant
      pneumococcus while a patient receives macrolide treatment. Two recent studies
      that included macrolide-susceptible and macrolide-resistant pneumococci showed
      that breakthrough bacteremia in patients receiving macrolide treatment occurred
      only with macrolide-resistant isolates. Study of bacteremic disease ensures the
      pathogenic role of the pneumococcus; however, it underestimates the true clinical
      impact of macrolide resistance.

PMID- 14733844
TI  - Antibiotics for Travelers: What's Good and What's Not.
AB  - International travel to exotic destinations continues to increase, as does the
      risk for illness during travel. Health problems during travel are common.
      Although many medical problems that travelers incur are noninfectious in origin
      (eg, injuries, environment-associated illness), travelers often are at risk for
      acquiring a variety of infections. Many travel-related infections also occur
      commonly in the developed world, whereas other infections of travelers may be
      geographically restricted to specific world regions and/or are infrequently
      encountered in developed nations. Antibiotics play an important role in the
      treatment and prevention of a variety of bacterial and parasitic infections in
      travelers. This article reviews antibiotics of particularly high utility to
      travelers, with emphasis on selected agents that, with appropriate advice from a
      travel medicine specialist, can be used safely for prophylaxis and self-treatment
      during travel. The role of antibiotics in selected high-risk travelers also is
      discussed.

PMID- 14733845
TI  - Nitazoxanide As Treatment of Intestinal Parasites in Children.

PMID- 14733846
TI  - Typhoid Fever.
AB  - Typhoid fever is caused by infection with Salmonella enterica serovar Typhi. The
      completion of the genome sequence of two Salmonella enterica serovar Typhi
      isolates is leading to new insights into the biology of this pathogen.
      Approximately 16 million cases occur worldwide each year. The lack of culture
      facilities in endemic areas and the poor performance of the Widal test means the
      disease is frequently unconfirmed. Simple new serologic tests are being developed
      and show promise. Resistance to chloramphenicol, ampicillin, and
      trimethoprim/sulfamethoxazole is widespread in Asia and some areas of Africa,
      although fully susceptible isolates have re-emerged in some countries.
      Fluoroquinolones, third-generation cephalosporins, and azithromycin are effective
      alternatives. Low-level fluoroquinolone resistance (indicated by resistance to
      nalidixic acid) is now common in Asia and results in a suboptimal response to
      fluoroquinolones. Two vaccines are licensed and others are being developed, but
      neither licensed vaccine is used in endemic areas as a public health measure.

PMID- 14733847
TI  - Yellow Fever Immunizations: Indications and Risks.
AB  - The yellow fever vaccine plays an essential role in protecting humans from yellow
      fever, and millions of doses are administered each year. The attenuated live
      virus vaccine has long been considered to be among the safest and most effective
      vaccines. Newly recognized rare, but sometimes fatal, adverse events associated
      with the vaccine have prompted scrutiny of the traditional recommendations for
      use of the vaccine and have raised questions about their pathogenesis. This paper
      describes the adverse events associated with the vaccine, reviews postulated
      reasons for the recent recognition of these events, discusses key research
      questions that need to be addressed in trying to understand their origin and risk
      factors, and reviews current indications for the use of the vaccine. Knowledge of
      the epidemiology of yellow fever is necessary to make informed recommendations.
      Current surveillance is inadequate to provide a precise exposure risk for most
      travelers.

PMID- 14733848
TI  - Prevention and Treatment of High-altitude Illness in Travelers.
AB  - High-altitude illness is the collective term for acute mountain sickness (AMS),
      high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE).
      These syndromes can affect unacclimatized travelers shortly after ascent to high
      altitude (especially higher than 2500 m). AMS is relatively common and usually is
      mild and self-limiting; HACE and HAPE are uncommon but life-threatening. Gradual
      ascent is the best strategy for preventing or minimizing high-altitude illness,
      although chemoprophylaxis may be useful in some situations. Acetazolamide remains
      the chemoprophylactic agent of choice, although other drugs, such as gingko
      biloba, are being investigated. Immediate descent remains the cornerstone of
      treatment for HACE and HAPE, although pharmacologic and hyperbaric therapies may
      facilitate this process.

PMID- 14733849
TI  - Cutaneous Larva Migrans.
AB  - International travel and increasingly exotic diets have resulted in an increase
      in cases of cutaneous larva migrans in industrialized countries. A broader
      spectrum of clinical presentation and complications of cutaneous larva migrans is
      recognized by clinicians. A new syndrome, eosinophilic enteritis, has been
      described in Australia and may be more widespread as new diagnostic tests are
      used more widely. Other causes of cutaneous migration, such as gnathostomiasis
      and sparganosis, should be considered, and a recent outbreak of gnathostomiasis
      in Mexico suggests that clinicians must be alert to these unusual infections
      arising in patients outside their traditional distribution.

PMID- 14733850
TI  - Dermatologic Infectious Diseases in International Travelers.
AB  - Skin lesions provide an important clue to the diagnoses of many infections in
      returned travelers. New information related to epidemiology, recognition,
      diagnosis, or management is described for the systemic infections--dengue fever,
      several of the rickettsial infections, African trypanosomiasis, and
      coccidioidomycosis. Many pathogens cause focal skin findings. Recent findings are
      presented for cutaneous leishmaniasis, Buruli ulcer, gnatho-stomiasis, cutaneous
      larva migrans, myiasis, tungiasis, and scabies. This paper describes the most
      common skin problems in returning travelers and outlines the types of infections
      that cause skin lesions, as defined by morphologic characteristics.

PMID- 14733851
TI  - Primary HIV Infection.
AB  - Primary HIV infection is a critical and highly dynamic time period in the course
      of HIV infection. The initial pathologic processes are important in determining
      long-term disease progression. In the absence of our ability to eradicate the
      virus, identifying individuals during primary HIV infection and performing
      interventions that optimize outcome are important to provide adequate care to a
      newly infected patient and, from a public health perspective, to identify sexual
      networks and provide a platform to reduce HIV exposures during a time of high
      viremia.

PMID- 14733852
TI  - Managing Syphilis in the HIV-infected Patient.
AB  - Syphilis has re-emerged in the United States and elsewhere, and clinicians caring
      for HIV-infected patients are challenged with syphilis diagnosis and management
      decisions. HIV alters the natural history of syphilis to an extent that is poorly
      understood, and initial presentation may be more varied in coinfected patients.
      Although commonly available diagnostic assays for syphilis should be interpreted
      as usual, such tests rely on antibody measurement and may be an imperfect
      indicator of active infection. Assessment of all available clinical and risk
      behavior data remains critically important in the diagnosis of syphilis in
      coinfected patients. Treatment of syphilis in such patients requires stage
      appropriate therapy, with careful serologic monitoring to assess response.
      Clinicians must have heightened appreciation of the role of frequent risk
      assessment, serologic screening, symptom recognition, and follow-up of treated
      patients, as well as an understanding of public health functions such as sex
      partner treatment and communicable disease reporting.

PMID- 14733853
TI  - [Efficacy preemptive therapy with ganciclovir for the prevention of
      cytomegalovirus disease in liver transplant recipients].
AB  - BACKGROUND AND OBJECTIVE: In liver transplant recipients the most frequent
      infection is that produced by cytomegalovirus (CMV). One of the methods to reduce
      the incidence of that infection is the CMV pp65 antigenemia-guided preemptive
      therapy with intravenous ganciclovir. PATIENTS AND METHOD: Liver transplant
      recipients were tested for CMV antigenemia at days 14, 28, 45, 60, 90 and 180
      postransplantation and when clinically indicated. Patients showing > 50/200.000
      leukocytes received ganciclovir 5 mg/kg/12 h for 14 days. Risk factors for active
      CMV disease where studied. RESULTS: 182 CMV seropositive patients where included
      in the study. 16 patients with > 50/200.000 leukocytes received ganciclovir as
      preemptive therapy. CMV disease appeared in 9/182 patients (4.9%): 2/16 who
      received PT and 7/166 among those who did not receive preemptive therapy. The
      only factor associated with increased incidence of CMV disease was to have
      missing samples for CMV antigenemia during the follow up (p < 0.0042; OR = 8,17;
      95% CI, 1.94-34.36). CONCLUSIONS: Ganciclovir antigenemia-guided preemptive
      therapy is associated with a low incidence of CMV disease. Bad adherence to the
      protocol of antigenemia samples increases the risk for CMV disease.

PMID- 14733854
TI  - [The consulting of internal medicine in primare care improves the efficacy of
      medical care].
AB  - BACKGROUND AND OBJECTIVE: Our aim was to evaluate the efficacy of the consulting
      of internal medicine (CIM) in primary care (PC) on the resolution of medical
      processes. PATIENTS AND METHOD: Prospective case-control study of a population of
      87,016 inhabitants during a 1-year period. Patients (2,167) jointly attended by
      family physicians (FP) and consulting internists (CI) who go weekly to the
      primary care center (PCC) to attend patients who otherwise would have been
      referred to specialized consultation (SC). As the control group 1,470 patients
      were randomly and simultaneously chosen among the total of 14.687 first medical
      referrals during the period of the study. RESULTS: We observed a significant
      reduction in: referrals to SC (22%; CI 95%, 18-26%); mean time for SC (23.6 days;
      CI 95%, 17.3-29.9 days); mean number of tests per patient ordered by FP (0.53; CI
      95%, 0.31-0.75) or by CIM (1.22; CI 95%, 1.02-1.40); mean time for patient
      information on those tests ordered by CIM (21.2 days; CI 95%, 8.5-33.9 days);
      mean time for the resolution of processes (39.4 days; CI 95%, 35.5-43.3 days);
      crossed SC rate (23.7%; CI 95%, 20.3-27.1%); and specialized follow-up visits
      (28.8%; CI 95%, 24.5-33.1%) (p < 0.005 in all cases). The resolution rate of
      processes (15%; CI 95%, 11-19%) and the discharge rate (41.6%; CI 95%, 35.5
      47.7%) were significantly higher for the CIM (p < 0.01 in both cases). The
      referral rate to SC showed a negative correlation (r = 0.81; p < 0.01) with the
      management quality, and it related to type of training, age and years of medical
      practice of the general practitioner (GP). The satisfaction of patients and GPs
      with the CIM was very high. CONCLUSIONS: CIM in PC improves the efficacy of
      specialized outpatient medical care.

PMID- 14733855
TI  - [Prevention of thromboembolism in patients with chronic atrial fibrillation in
      primary health care].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to evaluate the appropriateness of
      antithrombotic treatment administration in patients with chronic atrial
      fibrillation (CAF) attended in a health primary center. PATIENTS AND METHOD:
      Transverse and descriptive study; 416 patients diagnosed with CAF were included
      out of a population of 28,447. Age, sex, embolism risk factors, antithrombotic
      therapy, contraindications to anticoagulation and stratification risk variables
      were collected. After a bivariate analysis, a logistic regression model was done
      to analyze the variable associated with an incorrect antithrombotic therapy.
      RESULTS: 81% patients were given a correct antithrombotic therapy: 96.8% with a
      valvular-CAF pattern and 78.2% with a non-valvular CAF pattern. Older the
      patient, higher the percentage of incorrect antithrombotic administration (t =
      3.184; p = 0.002). A greater embolic risk was associated with a better
      antithrombotic treatment (p < 0.001). The existence of at least one risk factor
      was also associated with a correct administration (p < 0.001). Hypertension,
      mitral valvular heart disease and valvular prosthesis were factors associated
      with a correct antithrombotic therapy. In a multivariate analysis, limited
      quality of life, mitral valvular heart disease, hypertension and previous
      systemic embolism behaved all as protective factors of a wrong treatment. An age
      older than 80 years was associated with a risk of treatment which was 2.89 times
      higher than that of individuals with the same age or youngers (OR = 2.89; 95% CI,
      1.68-4.95). CONCLUSIONS: Most patients with CAF, both valvular and non-valvular,
      were properly given antithrombotic therapy. The main factor associated with an
      incorrect antithrombotic therapy was advanced age.

PMID- 14733856
TI  - [Treatment of latent tuberculosis among homeless population. Comparison between
      wo therapeutic approaches].
AB  - BACKGROUND AND OBJECTIVE: We aimed to compare treatment adherence and toxicity of
      isoniazide (H) (6 months) compared with rifampicine (R) + pirazinamide (Z) (2
      months) in homeless patients in latent tuberculous infection (LTBI). PATIENTS AND
      METHOD: Randomized and controlled prospective study. RESULTS: We included 172
      patients (116 males and 56 females) with an age average of 42.3 (12.8) years; 31
      (18%) had recent conversion and 72 (41.8%) had some risk factor of
      hepatotoxicity. Both bivariate and multivariate analysis (p < 0.001; OR = 5.15
      [2.34-11.35]) showed that the treatment was completed by 61.5% of patients
      administered the R+Z regimen, while it was completed only by 28.2% of those
      administered H for 6 months. Moreover, treatment was completed by 48.4% of
      Spanish or foreign patients with legal residence, while it was completed only by
      28.6% of immigrant patients with no legal residence (p = 0.044 in bivariate
      analysis). CONCLUSIONS: The R+Z regimen for 2 months as treatment of LTBI in
      homeless patients displays a higher adherence than H for 6 months. There were no
      differences in toxicity.

PMID- 14733857
TI  - [The internist as a consulting physician in primary health care].

PMID- 14733858
TI  - [Primary pulmonary hypertension: prospects for treatment].

PMID- 14733859
TI  - [Combined treatment with intravenous prostacyclin and sildenafil in patients with
      pulmonary hypertension: report of 4 cases].
AB  - BACKGROUND AND OBJECTIVE: Here we report the experience obtained from a combined
      treatment with intravenous (i.v) prostacyclin and oral sildenafil in patients
      with severe pulmonary hypertension (PHT) who had a poor response to prior
      treatment with prostacyclin alone. PATIENTS AND METHOD: Sildenafil was added to
      the treatment in four patients with PHT (primary in two patients and secondary to
      collagenosis in the other two) with no adequate response to i.v. prostacyclin
      treatment. The clinical course, 6minutes walking test and echocardiogram were
      evaluated. RESULTS: Initial sildenafil dose was 12.5 mg three times daily, which
      was increased up to 50 mg three times daily in one patient and up to 50 mg four
      times daily in the other three. The symptoms of right heart failure were
      controlled in all cases. Before the start of sildenafil administration, two
      patients had class III dyspnea and two patients had class IV dyspnea. Two
      patients converted to class I (previously class III and IV), and the other two
      converted to class II. The distance walked within 6 minutes increased (average
      increase 55%) and systolic pulmonary artery pressure decreased in all patients
      (average reduction 27%). Effects of sildenafil were substained. The only side
      effect seen was mild headache. CONCLUSIONS: Our experience supports the value of
      sildenafil in the treatment of PHT and suggests that combined treatment is useful
      for rescuing patients who fail to respond to initial treatment with i.v.
      prostacyclin.

PMID- 14733860
TI  - [Population attitude toward presumed consent legislation to cadaveric organ
      donation].

PMID- 14733861
TI  - [Stroke in young adults].
AB  - Stroke in young adults (15-45 years) is a rare condition. Up to 10% of patients
      with a first stroke admitted to the hospital belong in this age group. Stroke in
      the young patient is different from stroke in the elderly in several aspects such
      as etiology and prognosis. Usually, the management of stroke in young adults
      warrants an exhaustive etiological work-up. In this article, we review the most
      relevant issues in the study of young adults who suffer from stroke.

PMID- 14733862
TI  - [Advances in ostheochlast biology: the osteoprotegerin-RANK ligand system].
AB  - The differentiation and activation of osteoclasts specialized cells that degrade
      the bone matrix are decisively regulated by the osteoprotegerin (OPG)-RANK ligand
      (RANKL) paracrine system. The OPG is a soluble protein, similar to other members
      of the tumor necrosis factor receptor superfamily, which works as a decoy
      receptor of RANKL. The biologic activity of OPG counteracts the effects of RANKL
      by competing with the receptor activator of the nuclear factor *B (RANK);
      subsequently, the differentiation and activation of osteoclasts is inhibited and
      bone resorption reduced. The critical role of this pathway in the regulation of
      bone metabolism has been signalled by the finding of extreme phenotypes
      (osteoporosis vs. osteopetrosis) in animal models. Further studies with these
      factors will provide the development of drugs to treat osteoporosis and other
      metabolic bone diseases.

PMID- 14733863
TI  - [Congenital tracheoesophageal fistula, a rare cause of chronic cough in an
      adult].

PMID- 14733864
TI  - [Delirium after sudden interruption of nicotine consumption].

PMID- 14733865
TI  - [Mesial temporal epilepsy in a patient with asymetric hydrocephalus].

PMID- 14733866
TI  - [Changes in the spectrum of morbidity and mortality in hospital admissions of HIV
      infected patients during the HAART era].
AB  - BACKGROUND AND OBJECTIVE: After the introduction of highly active antiretroviral
      therapy (HAART), there was a decrease in hospital admissions and mortality
      associated with human immunodeficiency virus (HIV) infection. The objective of
      this study was to analyze the changes in mortality and morbidity during the HAART
      era. PATIENTS AND METHOD: We reviewed 1,343 hospital admissions from 610 HIV
      infected patients between January 1995 and December 2000. We analyzed the
      morbidity and mortality figures at the pre-HAART last biennium (1995-1996) and
      those at the first and second HAART biennium (1997-1998, HAART-1, and 1999-2000,
      HAART-2). RESULTS: Hospital admissions due to AIDS-defining illnesses decreased
      throughout the HAART era, whereas admissions caused by non-AIDS-defining
      illnesses increased (p < 0.001) with a significant growth in the frequency of
      respiratory tract infections (p = 0.004), digestive tract diseases (p < 0.001)
      and liver diseases (p = 0.03). There was a declining trend in hospital mortality
      throughout the study period. AIDS-defining illnesses decreased from the pre-HAART
      biennium to the HAART-1 and -2 periods (p = 0.03), whereas liver diseases
      increased (p = 0.03). CONCLUSIONS: In the HAART era, hospital admissions and
      mortality due to AIDS-defining illnesses continue to decrease. Nevertheless,
      there is a steady increase in the number of admissions and deaths of patients
      with non-AIDS-defining illnesses.

PMID- 14733867
TI  - [Subsets of CD8+ T cells in longterm asymptomatic vertically HIV-1 infected
      children].
AB  - BACKGROUND AND OBJECTIVE: HIV-infection has distinct patterns of disease
      progression with heterogeneous manifestations. We analyzed the subsets of CD8+ T
      cells in a group of long term asymptomatic (LTA) HIV-1-infected children who had
      stable CD4+ T cell counts (> 600/l). PATIENTS AND METHODS: Cross-sectional study
      in HIV-1-vertically infected children older than 7 years who were rated into two
      groups according to the clinical and immunological classification: a) LTA: 7
      asymptomatic HIV-1-infected children in A1, and b) rapid progressor (PR): 14 age
      matched C3 HIV-1-infected children. Controls included 17 age-matched uninfected
      children. Characterization of CD8+ T-cell subsets was done by three-color flow
      cytometry. RESULTS: LTA children displayed similar values of memory CD8+ T cells
      (CD8+CD45RO+, CD8+CD45RA-CD28+, CD8+ CD45RA-CD62L+) as controls but lower than PR
      children. LTA patients also showed similar values of naive CD8+ T cells
      (CD8+CD45RA+CD62L+, CD8+CD45RA+CD28+, CD8+CD45RA+, CD8+CD28+ and CD8+CD62L+) as
      controls but higher values than PR children. The values of CD8+CD38+ T cells were
      similar in LTA and controls but lower in PR. However, LTA children had higher
      values of CD8+HLA-DR+CD38+ and CD8+HLA-DR+ T cells than controls. Additionally,
      LTA patients had higher values of pre-effector CD8+ T cells than controls yet the
      values of effector CD8+ T-cells were similar in both LTA and controls. Moreover,
      the LTA group had lower values of CD8+CD11b+ T cells than controls. CONCLUSIONS:
      Asymptomatic HIV-1 infected children have an almost normal CD8+ subset
      distribution, with the exception of activated and pre-effector CD8+ T cells which
      were higher.

PMID- 14733868
TI  - [Epidemiological study of the GEICAM group about breast cancer in Spain (1990
      1993): El Alamo project].
AB  - BACKGROUND AND OBJECTIVE: The aim of the El Alamo project was to define the
      demographic and clinic characteristics, treatment and evolution of women with
      invasive breast cancer diagnosed in hospitals of the GEICAM group (Spanish Breast
      Cancer Research Group) between 1990 and 1993. PATIENTS AND METHOD: Data from
      4,532 patients were included. Forms were completed according to the medical
      history of patients, and collected in the GEICAM scientific office, where they
      were added to a data base. RESULTS: 32 hospitals from 19 provinces and 11
      regional communities participated in the study. Mean age of the 4,532 patients
      was 56.72 years, 1,428 (31.5%) were premenopausal and 2,988 (65.9%) were
      postmenopausal. Stage II tumors were most frequent (55.5%). Among patients with
      stage I, II and III at diagnosis, surgery was the first treatment in most
      (90.7%), radical mastectomy being the most frequent procedure performed (79.7%).
      70.4% of 1941 patients with positive axillary node and 37.4% of 1,806 patients
      without axillary affection received adjuvant chemotherapy with or without hormone
      therapy. CONCLUSIONS: El Alamo project represents the largest data base on breast
      cancer in Spain and the results are similar to those observed in other countries
      such as the USA.

PMID- 14733869
TI  - [Sexually transmitted infections in Barcelona beyond 2000].
AB  - BACKGROUND AND OBJECTIVE: Information about sexually transmitted infections (STI)
      in Barcelona is scarce. Sexual risk behaviors and some STI have recently
      increased. METHOD: Descriptive study of STI diagnosed at the STI Unit of
      Barcelona between 2001 and 2002. RESULTS: Some STI were more frequent among
      homosexual men. HIV coinfection in patients with syphilis was seen in 10/18
      homosexual men and 1/10 heterosexuals (p = 0.04). CONCLUSIONS: There is a
      resurgence of some STI in Barcelona. New preventive interventions are needed,
      especially addressed to homosexual men.

PMID- 14733870
TI  - [The long shadow of HIV/AIDS in hospitals].

PMID- 14733871
TI  - [Lymphocyte subpopulations in HIV infection].

PMID- 14733872
TI  - [Homocysteine in patients with diabetes mellitus].
AB  - Homocysteine is a sulphur aminoacid with a free thiol group which is not present
      in dietary protein. This aminoacid is a secondary f methionine by-product from
      cysteine metabolism. The pathogenic mechanisms of homocysteine in vascular damage
      have not been clarified. At present, it is no possible to develop an atherogenic
      and thrombogenic hypothesis. Yet high levels of homocysteine can cause
      endothelial damage, with increased thrombosis and atherosclerosis.
      Hyperhomocysteinemia has been reported in patients with diabetes mellitus type 1
      and type 2; the prevalence and secondary cardiovascular risk is higher in
      patients with diabetes type 2 than those with diabetes type 1. In patients with
      diabetes mellitus type 1, microvascular and macrovascular complications and
      neuropathy are found to be increased in those with hyperhomocysteinemia. In
      patients with diabetes mellitus type 2, the relationship between
      hyperhomocysteinemia, macrovascular complications and renal disease is unclear;
      however, a higher prevalence of macrovascular complications in diabetic patients
      with hyperhomocisteinemia is associated with a higher prevalence of renal
      disease. Moreover, patients with hyperhomocysteinemia have hypertension and
      dyslipemia. Multivariate regression analyses have shown an independent
      relationship between homocysteine and macrovascular complications. The
      relationship between retinopathy and homocysteine has not been clarified. In
      summary, hyperhomocysteinemia could be a risk factor accounting for chronic
      complications in diabetic patients. Nevertheless, it is necesary to perform more
      prospective and intervention studies to clarify the independent risk of
      homocysteine and thus assay alternative treatments.

PMID- 14733873
TI  - [Dyspnea, cough, hemoptysis and bilateral nodular lung infiltrates in a 62-year
      old male].

PMID- 14733874
TI  - [Levetiracetam hepatitis].

PMID- 14733876
TI  - [Usefulness of intrahospitalary infarction treatment registers in Spain].

PMID- 14733875
TI  - [Analysis of HOX11 gene in a patient with asplenia].

PMID- 14733877
TI  - [About clinical reports in the emergency setting].

PMID- 14733878
TI  - [Plasma leptin levels in patients with primary biliary cirrhosis and their
      relationship with degree of fibrosis].
AB  - OBJECTIVES: a) To analyze plasma leptin levels in patients with primary biliary
      cirrhosis (PBC) and b) to investigate the relationship between leptin levels and
      liver fibrosis stage in a cohort of patients with PBC. PATIENTS AND METHODS:
      Serum leptin levels were evaluated through radioimmunoassay in 30 patients with
      PBC (mean age: 37.2 +/- 11.0 years; range:19-75) and in 29 controls matched for
      age and weight. Venous blood obtained after a 12-hour fast was centrifuged in
      EDTA tubes. Weight, height and body mass index (BMI) were measured using standard
      methods. Hepatitis C virus RNA was determined using qualitative and quantitative
      polymerase chain reaction. In all patients liver biopsies were performed and the
      degree of fibrosis and extent of inflammatory infiltrate were evaluated. RESULTS:
      Plasma leptin levels in patients with PBC were lower than those obtained in
      control subjects (p<0.0001). No significant differences were found between the
      two groups in age, weight, height, BMI or body fat index. There was a clear
      increase in serum leptin levels according to histological stage of PBC (stage I:
      2.1 ng/ml; stage II: 4.3 ng/ml; stage III: 5.3 ng/ml; stage IV: 12.1 ng/ml;
      p<0.01) CONCLUSIONS: The present study demonstrates the correlation between
      leptin and stage of liver fibrosis in a cohort of patients with PBC, providing
      further evidence of the involvement of leptin in the process of liver fibrosis.

PMID- 14733879
TI  - [De novo hepatitis B with anti-HBc negative in a liver transplant recipient
      [corrected]].
AB  - De novo hepatitis B was diagnosed in a 47-year-old man 15 months after liver
      transplantation for end-stage alcoholic cirrhosis. Serum antibodies to hepatitis
      B core antigen (anti-HBc) were negative, and remained undetectable over 20 months
      of follow-up. The possible causes of negative serum anti-HBc despite of active
      hepatitis B virus infection are reviewed. Immunosuppression may underlie this
      phenomenon in similar cases.

PMID- 14733880
TI  - [Update in the treatment of chronic hepatitis B].

PMID- 14733881
TI  - [Evaluation of quality of life in digestive diseases].

PMID- 14733882
TI  - [Pegylated-interferon-induced diabetes mellitus type 1 in two patients with
      chronic hepatitis C].

PMID- 14733883
TI  - [Paravertebral mass as the first manifestation of hepatocarcinoma].

PMID- 14733884
TI  - [Perforation of Meckel's diverticulum by a foreign body: an unusual form of
      presentation of acute abdomen].

PMID- 14733885
TI  - [Irbesartan-induced acute hepatitis].

PMID- 14733886
TI  - Relationship between androgens, environmental factors and reproductive behavior
      in male white rhinoceros (Ceratotherium simum simum).
AB  - We conducted a longitudinal study of the endocrine activity of free-range male
      white rhinos. An enzyme immunoassay to measure androgens in the feces was
      developed and validated to show that it can be used to study testicular activity.
      We identified two fecal metabolites similar to testosterone and
      dihydrotestosterone. Several lines of evidence suggest that these metabolites
      clearly reflect testicular activity. Firstly, the stimulation of testicular
      activity with synthetic GnRH caused a 156% increase in androgen metabolite
      concentrations in the feces 1 day after treatment. Secondly, androgen metabolite
      concentrations increased with sexual maturity in rhinos, and finally there was a
      correlation between testosterone concentrations in plasma and androgen metabolite
      concentrations in feces. Using the method that we developed, it was possible to
      establish whether a relationship exists between androgen metabolite
      concentrations, the behavior and environmental factors. Adult territorial males
      (n = 5) had elevated androgen metabolite concentrations during months of high
      rainfall (September-February) compared to months of little or no rainfall (March
      August). The increase in concentrations coincided with the beginning of the rainy
      season, suggesting a seasonal trend in reproduction. This trend was confirmed by
      behavior observations showing both a higher frequency of conceptions within the
      first 4 months of increased androgen metabolite concentrations, and a higher
      number of inter-sexual conflicts, reflecting the initial aggression between the
      sexes during the consort period. It was also evident that males accompanying a
      receptive female had higher fecal androgen metabolite concentrations compared to
      being alone. The elevated levels were likely induced by female presence.

PMID- 14733887
TI  - Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive
      technique to monitor stress hormones.
AB  - In small animals like mice, the monitoring of endocrine functions over time is
      constrained seriously by the adverse effects of blood sampling. Therefore,
      noninvasive techniques to monitor, for example, stress hormones in these animals
      are highly demanded in laboratory as well as in field research. The aim of our
      study was to evaluate the biological relevance of a recently developed technique
      to monitor stress hormone metabolites in fecal samples of laboratory mice. In
      total, six experiments were performed using six male and six female mice each.
      Two adrenocorticotropic hormone (ACTH) challenge tests, two dexamethasone (Dex)
      suppression tests and two control experiments [investigating effects of the
      injection procedure itself and the diurnal variation (DV) of glucocorticoids
      (GCs), respectively] were conducted. The experiments clearly demonstrated that
      pharmacological stimulation and suppression of adrenocortical activity was
      reflected accurately by means of corticosterone metabolite (CM) measurements in
      the feces of males and females. Furthermore, the technique proved sensitive
      enough to detect dosage-dependent effects of the ACTH/Dex treatment and
      facilitated to reveal profound effects of the injection procedure itself. Even
      the naturally occurring DV of GCs could be monitored reliably. Thus, our results
      confirm that measurement of fecal CM with the recently established 5alpha
      pregnane-3beta,11beta,21-triol-20-one enzyme immunoassay is a very powerful tool
      to monitor adrenocortical activity in laboratory mice. Since mice represent the
      vast majority of all rodents used for research worldwide and the number of
      transgenic and knockout mice utilized as animal models is still increasing, this
      noninvasive technique can open new perspectives in biomedical and behavioral
      science.

PMID- 14733888
TI  - Hypophysectomy does not block sensitization to the dopamine agonist quinpirole or
      its modulation by the MAOI clorgyline.
AB  - Repeated administration of the dopamine agonist quinpirole induces behavioral
      sensitization in rats that is characterized by a four- to eight-fold increase in
      the amount of locomotion compared to an acute dose of quinpirole, in the absence
      of any increases in mouthing behavior. The monoamine oxidase (MAO) inhibitor,
      clorgyline, switches behavioral sensitization to quinpirole from that of
      locomotion to self-directed mouthing. The mechanism by which clorgyline produces
      this switch in behavioral sensitization is unknown, but is independent of the
      known effects of clorgyline, namely, inhibition of MAO, inhibition of striatal
      dopamine uptake, or stimulation of sigma and I(2) receptors. Because clorgyline
      also inhibits hypothalamo-pituitary-adrenal (HPA) axis function, and increased
      HPA activity facilitates the behavioral effects of psychostimulant drugs, the
      effects of clorgyline on quinpirole sensitization are possibly due to an
      inhibition of HPA function. Therefore, the present study examined whether HPA
      activity is required for sensitization to quinpirole, and whether clorgyline
      exerts its effects on quinpirole sensitization via inhibition of HPA function.
      Control and hypophysectomized rats were administered clorgyline (1 mg/kg, s.c.)
      or vehicle 90 min before each injection of quinpirole (0.5 mg/kg x 8, twice
      weekly) or saline. To assess the level of sensitization reached by control and
      hypophysectomized rats, test injections of quinpirole (0.0, 0.07, and 0.2 mg/kg)
      were administered. Chronic quinpirole administration produced equivalent levels
      of locomotor sensitization in control and hypophysectomized rats. Clorgyline was
      equally effective in blocking the development of locomotor sensitization in
      control and hypophysectomized rats, and in sensitizing self-directed mouthing.
      The present study suggests that (1). HPA function is not necessary for the
      development of quinpirole sensitization and, (2). clorgyline does not produce its
      effects on behavioral sensitization to quinpirole via an inhibition of HPA
      activity. Moreover, the observation that quinpirole sensitization develops
      normally in the absence of any pituitary endocrine function suggests that
      pituitary-gonadal and pituitary-thyroid axes activity are also not necessary for
      quinpirole sensitization to occur.

PMID- 14733889
TI  - Anthropometric analysis of homosexuals and heterosexuals: implications for early
      hormone exposure.
AB  - Early exposure to sex steroids is thought to be important in mediating the
      differentiation of male-typical sexual orientation. Bone morphology is a marker
      of childhood sex steroid exposure, because estrogens and androgens control sexual
      dimorphism in skeletal size. Anthropometric analysis of heterosexuals and
      homosexuals indicates that those bones, which become sexually dimorphic in
      childhood, but not those which become sexually dimorphic after puberty, are
      different in length in homosexuals and heterosexuals. Persons with a sexual
      preference for males have less long bone growth in the arms, legs and hands, than
      those with sexual preference for females. The data support the hypothesis that
      male homosexuals have had less steroid exposure during development than male
      heterosexuals and that female homosexuals have had greater steroid exposure
      during development than their heterosexual counterparts.

PMID- 14733890
TI  - Territorial aggression and hormones during the non-breeding season in a tropical
      bird.
AB  - The hormonal control of territorial aggression in male and female vertebrates
      outside the breeding season is still unresolved. Most vertebrates have regressed
      gonads when not breeding and do not secrete high levels of sex steroids. However,
      recent studies implicate estrogens in the regulation of non-breeding
      territoriality in some bird species. One possible source of steroids during the
      non-breeding season could be the adrenal glands that are known to produce sex
      steroid precursors such as dehydroepiandrosterone (DHEA). We studied tropical,
      year-round territorial spotted antbirds (Hylophylax n. naevioides) and asked (1).
      whether both males and females are aggressive in the non-breeding season and (2).
      whether DHEA is detectable in the plasma at that time. We conducted simulated
      territorial intrusions (STIs) with live decoys to male and female free-living
      spotted antbirds in central Panama. Non-breeding males and females displayed
      robust aggressive responses to STIs, and responded more intensely to decoys of
      their own sex. In both sexes, plasma DHEA concentrations were detectable and
      higher than levels of testosterone (T) and 17beta-estradiol (E(2)). In males,
      plasma DHEA concentrations were positively correlated with STI duration. Next, we
      conducted STIs in captive non-breeding birds. Captive males and females displayed
      robust aggressive behavior. Plasma DHEA concentrations were detectable in both
      sexes, whereas T was non-detectable (E(2) was not measured). Plasma DHEA
      concentrations of males were positively correlated with aggressive vocalizations
      and appeared to increase with longer STI durations. We conclude that male and
      female spotted antbirds can produce DHEA during the non-breeding season and DHEA
      may serve as a precursor of sex steroids for the regulation of year-round
      territorial behavior in both sexes.

PMID- 14733891
TI  - The nitric oxide pathway participates in estrous behavior induced by progesterone
      and some of its ring A-reduced metabolites.
AB  - Intracerebral and intravenous administration of progesterone (P) and its ring A
      reduced metabolites induces intense sexual behavior (lordosis and proceptivity)
      in estrogen-primed rats. The present study tested the hypothesis that the nitric
      oxide-cGMP-protein kinase G pathway is involved in the facilitation of sexual
      behavior induced by the intracerebroventricular (i.c.v.) administration of P (130
      ng) and its ring A-reduced metabolites 5alpha-dihydroprogesterone (5alpha-DHP; 13
      ng) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl; 13 ng). In Experiment 1,
      we tested the relevance of the nitric oxide/cGMP pathway by infusing a nitric
      oxide synthase inhibitor or a nitric oxide-dependent, soluble guanylyl cyclase
      inhibitor icv before progestin administration. The lordosis induced by P, 5alpha
      DHP and 5alpha,3alpha-Pgl was significantly reduced at 2 h after progestin
      infusion by the previous injection of either a nitric oxide synthase inhibitor or
      by a soluble guanylyl cyclase inhibitor. Lordosis behavior returned to control
      values by 4 h. In Experiment 2, i.c.v. infusion of the protein kinase G inhibitor
      KT5823 significantly inhibited the lordosis behavior induced by all three
      progestins at 2 h. These data support the hypothesis that the nitric
      oxide/cGMP/protein kinase G pathway is involved in the lordosis induced by P and
      some of its ring A-reduced metabolites.

PMID- 14733892
TI  - Melanocortin-5 receptor deficiency promotes defensive behavior in male mice.
AB  - The endogenous melanocortin, alpha-melanocyte-stimulating hormone (alpha-MSH), is
      a neurohormone secreted by the neurointermediate lobe of the pituitary. Alpha-MSH
      promotes intermale aggression in mice by influencing pheromone secretion, but the
      role of specific melanocortin receptors has not been determined. We assessed mice
      made deficient in the gene for the melanocortin-5 receptor (MC5R) to determine
      its role in pheromone-regulated behavior. In heterotypic pairs assessed in the
      social interaction test (SIT), MC5R-deficient mice exhibited less aggressive
      behavior and more defensive behavior than their wild-type opponents. By contrast,
      when assessed in homotypic pairs and against stimulus animals in the SIT, MC5R
      deficient and wild-type mice behaved similarly. Moreover, urine from MC5R
      deficient mice stimulated more aggression than did urine from wild-type mice. The
      results suggest that MC5R deficiency disinhibits an aggression-suppressing
      pheromonal signal.

PMID- 14733893
TI  - Female canaries produce eggs with greater amounts of testosterone when exposed to
      preferred male song.
AB  - Male birdsong has a great influence in the stimulation of female reproduction.
      However, female physiological responsiveness to song may depend on the degree of
      complexity of male song. This is expected because females of iteroparous
      organisms may increase their fitness by matching their reproductive investment to
      the predicted value of each reproductive attempt. To the extent that the
      expression of male ornaments is a signal of male quality, we expect females to
      increase their investment when paired to highly ornamented males. However, female
      investment may be cryptic and difficult to detect, such as androgen content in
      the eggs. In this study, we exposed female canaries (Serinus canaria) to
      attractive and unattractive song repertoires using a crossover design. As
      predicted, females invested greater concentrations of testosterone in their eggs
      when exposed to attractive repertoires than when exposed to unattractive
      repertoires. This implies that song repertoires convey important information
      about the reproductive value of a given male and suggests that testosterone
      deposition in egg yolk may be costly.

PMID- 14733894
TI  - The impact of left and right intracranial tumors on picture and word recognition
      memory.
AB  - This study investigated the effects of left and right intracranial tumors on
      picture and word recognition memory. We hypothesized that left hemispheric (LH)
      patients would exhibit greater word recognition memory impairment than right
      hemispheric (RH) patients, with no significant hemispheric group picture
      recognition memory differences. The LH patient group obtained a significantly
      slower mean picture recognition reaction time than the RH group. The LH group had
      a higher proportion of tumors extending into the temporal lobes, possibly
      accounting for their greater pictorial processing impairments. Dual coding and
      enhanced visual imagery may have contributed to the patient groups' similar
      performance on the remainder of the measures.

PMID- 14733895
TI  - Praxic skills in down and mentally retarded adults: evidence for multiple action
      routes.
AB  - Functional relationships between praxic performance and visual recognition
      ability of mentally retarded adults are discussed, in an attempt to integrate
      findings from developmental disorders of action with those described in the adult
      literature. Three groups of participants took part in the study: adults with
      Down's syndrome (D), Mentally Retarded adults (MR), and mental age-matched
      controls (C). Three experiments were conducted. A gesture production task
      (Experiment 1) aimed to test ability to demonstrate the object use under three
      different experimental conditions: first, participants could only see the
      objects; second, they were allowed to see as well as to touch the objects; and
      third, participants were presented with the object names. An object decision task
      (Experiment 2) assessed the participants' ability to access structural
      descriptions of objects from vision. An imitation task (Experiment 3) was
      administered in order to test for the presence of Ideomotor Apraxia. Our results
      suggest that the two pathological samples may use different processing routes to
      action.

PMID- 14733896
TI  - Time estimation in Alzheimer's disease and the role of the central executive.
AB  - The aim of this study was to evaluate the role of short-term memory and attention
      in time estimation. For this purpose we studied prospective time verbal
      estimation in 21 patients with Alzheimer's disease (AD), and compared their
      performance with that of 21 matched normal controls in two different conditions:
      during a digit span task and during an attentional task. Results showed that the
      performance of AD patients was significantly worse than that of the controls; the
      interaction between group and condition was significant. We suggest a role of
      attentional-executive functions in prospective time estimation.

PMID- 14733897
TI  - Sex differences for selective forms of spatial memory.
AB  - In the present study, a systematic comparison of sex differences for several
      tests of spatial memory was conducted. Clear evidence for more accurate male
      performance was obtained for precise metric positional information in a
      wayfinding task and in an object location memory task. In contrast, no sex
      difference characterized topological information processing (object-to-position
      assignment). Together, these findings provide further insight in the specificity
      of sex differences in spatial memory and in the functional architecture of
      spatial memory. Implications for the relevant evolutionary basis are discussed.

PMID- 14733898
TI  - Memory for faces dissociates from memory for location following anterior temporal
      lobectomy.
AB  - It has been suggested that the right and left mesial temporal lobes are
      specialized for processing different types of information for long-term memory
      (LTM). Although findings have been consistent in regard to the dominant role of
      the left mesial temporal lobe (MTL) in verbal memory, the role of the right MTL
      in non-verbal memory remains debatable. Given the existence of two cortical
      pathways specialized for processing different types of visuospatial information,
      we examined whether memory processing for these two types of information might
      also be differentially localized. The effect of unilateral anterior temporal
      lobectomy (ATL) was compared for memory for unfamiliar faces and a novel sequence
      of spatial locations in 86 ATL patients (left ATL (LATL) = 35; right ATL (RATL) =
      51) pre- and post-surgery to examine the contributions of right and left MTL
      structures to LTM for pattern and spatial information. Memory for spatial
      location was not related to side of ATL or time of testing. On the facial memory
      task, RATL patients showed impairments relative to LATL patients prior to
      surgery, which became magnified after surgery. These results extend the proposed
      dissociation between an occipitotemporal and an occipitoparietal pathway for
      processing visuospatial information by demonstrating dissociations in LTM systems
      for these two types of information. Lesions in the right MTL, adjacent to the
      cortical structures believed to be specialized for facial recognition,
      specifically impair the memory encoding of new faces, but not spatial locations.

PMID- 14733899
TI  - Manipulation of frontal brain asymmetry by cognitive tasks.
AB  - The purpose of the present study was to evaluate whether verbal fluency tasks may
      specifically induce relatively greater left than right hemispheric activation in
      the dorsolateral prefrontal cortex. The effectiveness of the manipulation was
      evaluated by EEG, which was recorded during performance of the verbal fluency
      task and during two control conditions, i.e., a baseline condition without
      cognitive demands, and a mental arithmetic task, respectively. The results
      demonstrate that the desired effect can only be achieved in individuals with good
      performance on the verbal fluency task. Good and poor performers do not only
      differ in lateral asymmetry, but also in the most affected region within the
      prefrontal cortex. Whereas good performers show relatively increased activation
      in the cortical region and hemisphere putatively most specialized for this kind
      of task (i.e., the left dorsolateral frontal cortex), poor performers show a
      marked shift of frontopolar asymmetry to the right.

PMID- 14733900
TI  - Line-bisecting performance in highly skilled athletes: Does preponderance of
      rightward error reflect unique cortical organization and functioning?
AB  - A line-bisecting test was administered to 250 highly skilled right-handed
      athletes and a control group of 60 right-handed age matched non-athletes. Results
      revealed that athletes made overwhelmingly more rightward errors than non
      athletes, who predominantly bisected lines to the left of the veridical center.
      These findings were interpreted in the context of previous EEG research on
      athletes and brain localization studies of select personality traits. A
      preliminary theory (Group Cortical Organization and Activation Theory) that
      highly skilled athletes and other specific homogeneous populations may have
      developed a unique cortical organization or response system that mediates
      relative tendencies in cerebral activation was advanced. The potential utility of
      the line-bisecting test as an assessment and intervention tool in sports was
      discussed.

PMID- 14733901
TI  - A TMS study of the ventral projections from V1 with implications for the finding
      of neural correlates of consciousness.
AB  - The study of subliminal perception in normal and brain lesioned subjects has long
      been of interest to scholars studying the neural mechanisms behind conscious
      vision. Using brief durations and a developed methodology of introspective
      reporting, we present an experiment with visual stimuli that gives rise to little
      or no subliminal perception under normal viewing conditions. Coupled with
      transcranial magnetic stimulation, however, we find a dissociation between
      correctness and conscious awareness. Furthermore, we find support for the
      hypothesis that the ventral projection streams from V1 are necessary for visual
      consciousness.

PMID- 14733902
TI  - Differences in induced brain activity during the performance of learning and
      working-memory tasks related to intelligence.
AB  - Thirteen high intelligent (H-IQ) and 13 low intelligent (L-IQ) individuals solved
      two figural working-memory (WM) tasks and two figural learning tasks while their
      EEG was recorded. For the WM tasks, only in the theta band group related
      differences in induced event-related desynchronization/synchronization (ERD/ERS)
      were observed. L-IQ individuals displayed greater theta synchronization in the
      later phases of task completion (1000-2000 ms) as compared to H-IQ individuals.
      For the learning tasks group related differences in the three alpha bands were
      observed. In the upper alpha band L-IQ individuals showed greater ERD in the
      frontal brain areas, whereas H-IQ individuals displayed greater ERD in the
      parieto-occipital brain areas.

PMID- 14733903
TI  - Temporal organization of the brain: Neurocognitive mechanisms and clinical
      implications.
AB  - The synchrony between the individual brain and its environment is maintained by a
      system of internal clocks that together reflect the temporal organization of the
      organism. Extending the theoretical work of Edelman and others, the temporal
      organization of the brain is posited as functioning through "re-entry" and
      "temporal tagging" and binds the wide range of possible times to a unified
      cognitive experience which is held in unison with the outside world. Dysfunction
      in this system is reflected in the temporal discord seen in cases of aging, sleep
      disorder, jet-lag, and shift-work, as well as in mental disorders and drug
      induced changes in consciousness. The extent to which neuroendocrine structures
      contribute to the neurocognitive mechanisms which underlie consciousness has so
      far not been explored. Therefore, neuroendocrine mechanisms contributing to the
      temporal organization of the brain are reviewed. It is concluded that time-and
      its neuroendocrine correlate melatonin-is a binding principle for organizing
      conscious experience.

PMID- 14733904
TI  - Pre-attentive mental processing of music expectation: event-related potentials of
      a partially violating and resolving paradigm.
AB  - Auditory event-related potentials (ERPs) were investigated in an oddball paradigm
      to verify electrophysiological evidence of music expectation, which is a key
      component of artistic presentation. The non-target condition consisted of four
      chord harmonic chord sequences, while the target condition was manifested by a
      partially violating third chord and a resolving fourth chord. The results showed
      that the specific mismatch negativity (MMN) elicited in the resolving chord is as
      robust as that elicited in the partially violating chord. Moreover, the P3b
      (P300) elicited in the resolving chord was smaller than the one in the violating
      chord. Taken together these data indicates that the human brain pre-attentatively
      may be able to anticipate a subsequent resolving chord when music expectation is
      generated by a partially violating chord.

PMID- 14733905
TI  - Na(+)-D-glucose cotransporter in muscle capillaries increases glucose
      permeability.
AB  - By immunohistochemistry, we demonstrated the localization of the Na(+)-D-glucose
      cotransporter SGLT1 in capillaries of rat heart and skeletal muscle, but not in
      capillaries of small intestine and submandibular gland. mRNA of SGLT1 was
      identified in skeletal muscle and primary cultured coronary endothelial cells.
      The functional relevance of SGLT1 for glucose transport across capillary walls in
      muscle was tested by measuring the extraction of D-glucose from the perfusate
      during non-recirculating perfusion of isolated rat hindlimbs. In this model, D
      glucose extraction from the perfusate is increased by insulin which accelerates D
      glucose uptake into myocytes by increasing the concentration of glucose
      transporter GLUT4 in the plasma membrane. The insulin-induced increase of D
      glucose extraction from the perfusate was abolished after blocking SGLT1 with the
      specific inhibitor phlorizin. The data show that SGLT1 in capillaries of skeletal
      muscle is required for the action of insulin on D-glucose supply of myocytes.

PMID- 14733906
TI  - Analysis of post-lysosomal compartments.
AB  - Lysosomes are acidic intracellular compartments and are regarded as degradative
      and the end point, of the endocytic pathway. Here we provide evidence for the
      generation of acid hydrolase poor and non-acidic post-lysosomal compartments in
      NRK cells that have accumulated non-digestible macromolecules, Texas red-dextran
      (TR-Dex), within lysosomes. When TR-Dex was fed to the cells for 6h, most of the
      internalized TR-Dex colocalized with a lysosomal enzyme, cathepsin D. With an
      increase in the chase period, however, the internalized TR-Dex gradually
      accumulated in cathepsin D-negative vesicles. These vesicles were positive for a
      lysosomal membrane protein, LGP85, and their formation was inhibited by treatment
      of the cells with U18666A, which impairs membrane transport out of late
      endosomal/lysosomal compartments, thereby suggesting that the vesicles are
      derived from lysosomes. Interestingly, these compartments are non-acidic as
      judged for the DAMP staining. The results, therefore, suggest that the excess
      accumulation of non-digestible macromolecules within lysosomes induces the
      formation of acid hydrolase poor and non-acidic post-lysosomal compartments. The
      fact that treatment of the cells with lysosomotropic amines or a microtubule
      depolymerization agent resulted in extensive colocalization of TR-Dex with
      cathepsin D further indicates that the formation of the post-lysosomal
      compartments depends on the lysosomal acidification and microtubule organization.
      Furthermore, these results suggest bi-directional membrane transport between
      lysosomes and the post-lysosomal compartments, which implies that the latter are
      not resting compartments.

PMID- 14733907
TI  - A role of activated Sonic hedgehog signaling for the cellular proliferation of
      oral squamous cell carcinoma cell line.
AB  - Sonic hedgehog (Shh) is a secreted morphogen crucial for appropriate cellular
      proliferation during mammalian development. The activated Shh signaling is known
      to predispose to human tumors such as medulloblastoma and basal cell carcinoma,
      while a role of Shh signaling in the other common tumors is still controversial.
      Here we showed the overexpression of Shh in five cell lines among 14 human oral
      squamous cell carcinoma (OSCC) cell lines. One of the Shh-expressing OSCC cell
      lines HSQ-89 showed the inhibition of G1/S transition and apoptotic cell death by
      treatment with Cyclopamine, a steroidal alkaloid that blocks the intracellular
      Shh signaling. Furthermore, we found that treatment with Y-27632, a specific
      inhibitor of Rho-associated kinase, mimicked the effect of Cyclopamine on the
      cell cycle progression of HSQ-89. Our study revealed the involvement of activated
      Shh signaling in the cellular proliferation of OSCC cells, indicating Shh
      signaling might be a good therapeutic target for OSCC.

PMID- 14733908
TI  - Insulin signaling and glucose homeostasis in mice lacking protein tyrosine
      phosphatase alpha.
AB  - Studies in cultured cells have implicated protein tyrosine phosphatase alpha
      (PTPalpha) as a potential regulator of insulin signaling. The physiological role
      of PTPalpha in insulin action was investigated using gene-targeted mice deficient
      in PTPalpha. PTPalpha-null animals had normal body weights and circulating levels
      of glucose and insulin in random fed and fasted states. In glucose and insulin
      tolerance tests, their efficiency of blood glucose clearance was comparable to
      wild-type mice. Kinetics and extents of insulin-stimulated insulin receptor and
      IRS-1 tyrosine phosphorylation were similar in wild-type and PTPalpha(-/-) liver,
      muscle, and adipose tissue. However, the association of IRS-1 and PI 3-K was
      altered in PTPalpha(-/-) liver, with increased insulin-independent and reduced
      insulin-stimulated association compared to wild-type samples. This did not affect
      activation of the downstream signaling effector Akt. Our data indicate that
      PTPalpha is not a negative regulator of insulin signaling and does not perform an
      essential role in mediating the physiological action of insulin.

PMID- 14733909
TI  - Calcium binding to biliary mucins is dependent on sodium ion concentration:
      relevance to cystic fibrosis.
AB  - Because hypersecretion of gallbladder (GB) mucus occurs in gallstone formation
      and because binding of Ca(2+) to biliary lipids only accounts for 50% of the
      total Ca(2+) in GB bile, we investigated the binding of Ca(2+) to human biliary
      mucin. Biliary mucin was purified from GB bile and binding to Ca(2+) studied.
      Scatchard plot analysis suggested two binding sites. Removal of sialic acid by
      neuraminidase resulted in 10% reduction of Ca(2+) binding, whereas, sulfatase
      treatment reduced Ca(2+) binding by 30%. Using a hypotonic NaCl solution, Ca(2+)
      binding to mucin increased curvilinearly with mucin concentration. However,
      binding decreased with increasing ionic strength of the NaCl solution. We
      conclude that binding of Ca(2+) to mucin is effected mainly through sulfate.
      Binding to Ca(2+) can be displaced by Na(+). Ca(2+) binding to mucins is enhanced
      in the setting of low Na(+) concentrations. This phenomenon has pathophysiologic
      implications for the formation of thick mucus in cystic fibrosis epithelia.

PMID- 14733910
TI  - Molecular hierarchy in neurons differentiated from mouse ES cells containing a
      single human chromosome 21.
AB  - Defects in neurogenesis and neuronal differentiation in the fetal brain of Down
      syndrome (DS) patients lead to the apparent neuropathological abnormalities and
      contribute to the phenotypic characters of mental retardation, and premature
      development of Alzheimer's disease, those being the most common phenotype in DS.
      In order to understand the molecular mechanism underlying the cause of phenotypic
      abnormalities in the DS brain, we have utilized an in vitro model of TT2F mouse
      embryonic stem cells containing a single human chromosome 21 (hChr21) to study
      neuron development and neuronal differentiation by microarray containing 15K
      developmentally expressed cDNAs. Defective neuronal differentiation in the
      presence of extra hChr21 manifested primarily the post-transcriptional and
      translational modification, such as Mrpl10, SNAPC3, Srprb, SF3a60 in the early
      neuronal stem cell stage, and Mrps18a, Eef1g, and Ubce8 in the late
      differentiated stage. Hierarchical clustering patterned specific expression of
      hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation,
      such as Syngr2, Dncic2, Eif3sf, and Peg3.

PMID- 14733911
TI  - Antioxidant action of L-alanine: heme oxygenase-1 and ferritin as possible
      mediators.
AB  - The amino acid L-alanine has been shown to exert long-term cytoprotection by as
      yet unidentified molecular mechanisms. Using cultured human endothelial cells
      (ECV 304), the present study investigates the effect of L-alanine on hydrogen
      peroxide-mediated cytotoxicity and expression of the antioxidant stress proteins,
      heme oxygenase-1 (HO-1) and ferritin. Pretreatment with L-alanine (0.3-3mM)
      protected endothelial cells from hydrogen peroxide-dependent cytotoxicity and
      increased the surviving endothelial cell fraction by 76%. The described
      protection was associated with a significant induction of heme oxygenase activity
      and ferritin protein synthesis. A protective effect similar to L-alanine was
      observed when preincubating the cells with iron-free apoferritin or the
      antioxidant HO-1 product, bilirubin. The present study demonstrates that L
      alanine stimulates expression of the antioxidant defense proteins HO-1 and
      ferritin in endothelial cells. Increased heme oxygenase activity and ferritin
      expression improve endothelial dysfunction suggesting an antiatherogenic
      potential of L-alanine.

PMID- 14733912
TI  - Cloning and functional characterization of resistin-like molecule gamma.
AB  - Resistin, a recently discovered hormone that may play a crucial role in obesity
      associated diabetes, is the founding member of a novel family of cysteine-rich
      proteins that are secreted by specific cell types. Three other members of this
      family have been described to date and were termed resistin-like molecules
      (RELMs). Here we describe the cloning and functional characterization of
      RELMgamma. The mouse RELMgamma-cDNA encodes a protein of 117 amino acids that
      contains a signal peptide leading to secretion of the protein. By Northern
      blotting the RELMgamma-mRNA is detectable in bone marrow, spleen, and lung as
      well as in peripheral blood granulocytes. Promyelocytic HL60 cells transfected
      with a RELMgamma expression plasmid have an increased proliferation rate compared
      to mock-transfected cells and display an altered response to retinoic acid
      induced granulocytic differentiation. Taken together, these data provide the
      first experimental evidence that RELMgamma is a secreted molecule with a
      restricted expression pattern that may play a role in promyelocytic
      differentiation.

PMID- 14733913
TI  - IL-6 plays a critical role in the synergistic induction of human serum amyloid A
      (SAA) gene when stimulated with proinflammatory cytokines as analyzed with an SAA
      isoform real-time quantitative RT-PCR assay system.
AB  - Serum amyloid A (SAA) is known to be a precursor of amyloid A (AA) protein in AA
      (secondary) amyloidosis and SAA1 to be mainly involved in AA amyloidosis. We
      established an SAA isoform real-time quantitative RT-PCR assay and found that
      beta-2 microglobulin is more stable as an internal control than GAPDH and beta
      actin for our system. Either IL-6 and IL-1beta or IL-6 and TNFalpha, but not IL
      1beta and TNFalpha, induced the synergistic induction of SAA1 and SAA2 genes.
      Anti-IL-6 receptor monoclonal antibody completely inhibited the synergistic
      induction of SAA1 and SAA2 during triple stimulation with IL-6, IL-1beta, and
      TNFalpha, but, IL-1 receptor antagonist or anti-TNFalpha monoclonal antibody was
      only partially inhibited in HepG2, Hep3B, and PLC/PRF/5 cells. Although the SAA1
      promoter has no STAT3 consensus sequence, the JAK2 inhibitor-AG490 reduced SAA1
      gene expression to 30%, suggesting the involvement of STAT3. We were able to
      demonstrate that IL-6 plays a critical role in the synergistic induction of human
      SAA gene when stimulated with proinflammatory cytokines.

PMID- 14733914
TI  - Suppression of 3-deoxyglucosone and heparin-binding epidermal growth factor-like
      growth factor mRNA expression by an aldose reductase inhibitor in rat vascular
      smooth muscle cells.
AB  - Reactive carbonyl compounds and oxidative stress have been recently shown to up
      regulate the expression of heparin-binding epidermal growth factor-like growth
      factor (HB-EGF), a potent mitogen for vascular smooth muscle cells (SMCs)
      produced by SMC themselves. Because the polyol pathway has been reported to
      influence the formation of carbonyl compounds and the oxidative stress in various
      cells, we conducted this study to investigate whether the polyol pathway affects
      HB-EGF expression along with the generation of carbonyl compounds and the
      oxidative stress in SMCs. We found that, compared with those cultured with 5.5mM
      glucose, SMCs cultured with 40 mM glucose showed the accelerated thymidine
      incorporation, elevated levels of intracellular sorbitol, 3-deoxyglucosone (3
      DG), advanced glycation end products (AGEs), and thiobarbituric acid-reactive
      substances (TBARS) along with the enhanced expression of HB-EGF mRNA. An aldose
      reductase inhibitor (ARI), SNK-860, significantly inhibited all of these
      abnormalities, while aminoguanidine suppressed 3-DG levels and HB-EGF mRNA
      expression independent of sorbitol levels. The results suggest that the polyol
      pathway may play a substantial role in SMC hyperplasia under hyperglycemic
      condition in part by affecting HB-EGF mRNA expression via the production of
      carbonyl compounds and oxidative stress.

PMID- 14733915
TI  - Bcl-2 enhances neurite extension via activation of c-Jun N-terminal kinase.
AB  - Recent studies suggest that Bcl-2 may play an active role in neuronal
      differentiation. Here, we showed a marked neurite extension in MN9D dopaminergic
      neuronal cells overexpressing Bcl-2 (MN9D/Bcl-2) or Bcl-X(L) (MN9D/Bcl-X(L)). We
      found a specific increase in phosphorylation of c-Jun N-terminal kinase (JNK)
      accompanied by neurite extension in MN9D/Bcl-2 but not in MN9D/Bcl-X(L) cells.
      Consequently, neurite extension in MN9D/Bcl-2 but not in MN9D/Bcl-X(L) cells was
      suppressed by treatment with SP600125, a specific inhibitor of JNK. Inhibition of
      other mitogen-activated protein kinases-including p38 and extracellular signal
      regulated kinase-did not affect Bcl-2-mediated neurite extension in MN9D cells.
      While the expression levels of such protein markers of maturation as SNAP-25,
      phosphorylated NF-H, and neuron-specific enolase were increased in MN9D/Bcl-2
      cells, only upregulation of SNAP-25 was inhibited after treatment with SP600125.
      Thus, the JNK signal activated by Bcl-2 seems to play an important role during
      morphological and certain biochemical differentiation in cultured dopaminergic
      neurons.

PMID- 14733916
TI  - Differential expression of electrogenic NBC1 (SLC4A4) variants in rat kidney and
      pancreas.
AB  - The purpose of this study was to determine expression and localization of NH(2)
      terminal variants of the electrogenic Na(+)-HCO(3)(-) co-transporter NBC1
      (SLC4A4) in the rat kidney and pancreas. We generated two anti-peptide
      antibodies: alpha333 against the "mste" start (kidney; kNBC1) and alpha332
      against the "mede" start (pancreas; pNBC1). Transcripts for both NBC1 variants
      were detected in kidney and pancreas by RT-PCR, though kNBC1 was more prominent
      in the kidney and pNBC1 was more prominent in the pancreas. Similar protein
      expression levels were detected by immunoblotting of plasma membranes (PM) from
      kidney cortex and pancreas. Immunohistochemistry with alpha333 recognized the
      "mste"-epitope in the basolateral plasma membrane (BLM) of renal proximal tubule.
      The "mede"-protein (alpha332) was similarly localized although staining was much
      less and more diffuse. In the pancreas, alpha332 stained BLM of acinar and duct
      cells. Some isolated duct cells were also stained at the apical PM. The "mste"
      protein (alpha333) was absent in acinar cells but was located at the apical PM of
      duct cells. The data indicate that the two NH(2)-terminal NBC1 variants are co
      expressed in kidney and pancreas, where they may contribute to HCO(3)(-)
      transport and pH regulation.

PMID- 14733917
TI  - Kidney-targeted naked DNA transfer by retrograde injection into the renal vein in
      mice.
AB  - We recently developed a novel kidney-targeted gene transfer technique in rats,
      using the retrograde renal vein injection of naked plasmid DNA. Many animal
      disease models are created in mice by transgenic or knockout technologies.
      However, it is much harder to perform renal vein injection in mice than in rats
      because they have a thin and short vein. Here we transferred the mouse
      interleukin (IL)-10 gene into mice by retrograde renal vein injection, using an
      IL-10 and immunoglobulin fusion protein (IL-10/Fc) (96-kDa) expression plasmid,
      pCAGGS-IL10/Fc. We observed a dose-response relationship between serum IL-10
      levels and the amount of injected DNA. The serum IL-10 levels peaked at day 1 and
      then were sustained for at least 2 weeks. These results demonstrate that the
      kidney-targeted naked plasmid DNA transfer of mice by retrograde renal vein
      injection can be achieved, and the kidney serves as a depot organ for the
      production of large proteins.

PMID- 14733918
TI  - Screening of Hsp105alpha-binding proteins using yeast and bacterial two-hybrid
      systems.
AB  - Hsp105alpha is a 105-kDa stress protein, which is expressed constitutively at
      especially high levels in the brain compared with other tissues in mammals, and
      is also induced by a variety of stressors. Recently, we have shown that
      Hsp105alpha binds to alpha-tubulin and prevents the heat-induced disaggregation
      of microtubules. To further elucidate the function of Hsp105alpha, we searched
      for Hsp105alpha-binding proteins by screening a mouse FM3A cell library and human
      and mouse brain cDNA libraries using the yeast and bacterial two-hybrid systems.
      We showed here that Hsp105alpha interacted with several cellular proteins, such
      as cofilin, dynein light chain 2A, alpha-adducin, ubiquitin activating enzyme E1,
      phosphoglycerate kinase 1, and platelet-activating factor acethylhydrolase alpha1
      subunit. The interaction was validated by the results of a pull-down assay and
      indirect immunofluorescence analysis. The significance of Hsp105alpha and
      Hsp105alpha-binding proteins in cells was discussed.

PMID- 14733919
TI  - Angiotensin II type 1 receptor blockade attenuates renal fibrogenesis in an
      immune-mediated nephritic kidney through counter-activation of angiotensin II
      type 2 receptor.
AB  - The relative roles of angiotensin II (Ang II) type 1 receptor (AT(1)R) and Ang II
      type 2 receptor (AT(2)R) in immune-mediated nephritis are unknown, and the effect
      of the blockade of AT(1)R and its indirect counter-activation of AT(2)R relative
      to the anti-fibrotic action in this disease is unclear. To address this question,
      we studied the role of AT(1)R and AT(2)R in anti-glomerular basement membrane
      nephritis in SJL mice. Groups of mice were treated with either an AT(1)R
      antagonist (CGP-48933; CGP group), an AT(2)R antagonist (PD-123319; PD group),
      both (CGP/PD group), or a vehicle (PCt group) from Day 29 to 56. At Day 56 post
      treatment, fibrosis-related parameters such as interstitial matrix deposition,
      and the expression of genes of TGF-beta1, plasminogen activator inhibitor-1, and
      type I collagen were significantly reduced in the kidney in the CGP group. There
      were no significant effects on these parameters in the PD group. However, this
      anti-fibrotic action by CGP-48933 was totally abolished by co-treatment with PD
      123319 in the CGP/PD group. The gene expression of renin was significantly
      increased in the kidneys in the CGP and CGP/PD groups, suggesting that CGP-48933
      had increased Ang II generation in those groups. In conclusion, counter
      activation of AT(2)R by increased Ang II under AT(1)R blockade likely conferred
      an anti-fibrotic protection in this model.

PMID- 14733920
TI  - FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced
      expression of sodium phosphate cotransporter type IIa.
AB  - Fibroblast growth factor (FGF)-23 was identified as a causative factor of tumor
      induced osteomalacia and also as a responsible gene for autosomal dominant
      hypophosphatemic rickets. To clarify the pathophysiological roles of FGF-23 in
      these diseases, we generated its transgenic mice. The transgenic mice expressing
      human FGF-23 reproduced the common clinical features of these diseases such as
      hypophosphatemia probably due to increased renal phosphate wasting,
      inappropriately low serum 1,25-dihydroxyvitamin D level, and rachitic bone. The
      renal phosphate wasting in the transgenic mice was accompanied by the reduced
      expression of sodium phosphate cotransporter type IIa in renal proximal tubules.
      These results reinforce the notion that the excessive action of FGF-23 plays a
      causative role in the development of several hypophosphatemic
      rickets/osteomalacia.

PMID- 14733921
TI  - Direct reciprocal effects of resistin and adiponectin on vascular endothelial
      cells: a new insight into adipocytokine-endothelial cell interactions.
AB  - Resistin is an adipocytokine which plays a role in the development of insulin
      resistance. In this study, we investigated the direct effect of resistin on
      vascular endothelial cells. Resistin induced the expression of adhesion molecules
      such as VCAM-1 and ICAM-1, and long pentraxin 3, a marker of inflammation. The
      induction of VCAM-1 by resistin was inhibited partially by pitavastatin.
      Moreover, the induction of VCAM-1 and ICAM-1 by resistin was inhibited by
      adiponectin, an adipocytokine that improves insulin resistance. Taken together,
      these results suggest that the balance in the concentrations of adipocytokines
      such as resistin and adiponectin determines the inflammation status of
      vasculature, and in turn the progress of atherosclerosis.

PMID- 14733922
TI  - Differentiation of human adipose tissue stem cells using extracts of rat
      cardiomyocytes.
AB  - We report the differentiation of human adipose tissue stem cells (ATSCs) to take
      on cardiomyocyte properties following transient exposure to a rat cardiomyocyte
      extract. Reversibly permeabilized ATSCs were incubated for 1h in a nuclear and
      cytoplasmic extract of rat cardiomyocytes, resealed with CaCl(2), and cultured.
      Three weeks after exposure to extract, ATSCs expressed several cardiomyocyte
      markers including sarcomeric alpha-actinin, desmin, and cardiac troponin I, and
      displayed targeted expression of the gap junction protein connexin 43. Formation
      of binucleated and striated cells, and spontaneous beating in culture were also
      observed. A low proportion of intact ATSCs exposed to the extract also showed
      signs of alpha-actinin and connexin 43 expression. Additional evidence of
      differentiation was provided by induction of expression of nuclear lamin A/C, a
      marker of terminally differentiated cells, and a remarkable increase in cell
      cycle length. Together with our previous data, this study suggests that
      alteration of cell fate using cellular extracts may be applied to multiple cell
      types. Cell extracts may also prove useful for investigating the molecular
      mechanisms of stem cell differentiation.

PMID- 14733923
TI  - A Ca(2+)-dependent protein kinase with characteristics of protein kinase C in
      leaves and mesophyll cell protoplasts from Digitaria sanguinalis: possible
      involvement in the C(4)-phosphoenolpyruvate carboxylase phosphorylation cascade.
AB  - In mesophyll cells (MC) of Digitaria sanguinalis, the C(4)-phosphoenolpyruvate
      carboxylase (C(4)-PEPC) initiating the photosynthetic pathway is controlled by a
      complex light-dependent phosphorylation process. We showed previously that the
      transduction cascade involves the phosphoinositide pathway and a Ca(2+)-dependent
      step, which precedes the upregulation of the PEPC kinase (PEPCk). We have now
      further characterized the cascade component requiring Ca(2+). A Ca(2+)-dependent
      protein kinase that shows several characteristics of the conventional type of
      mammalian protein kinase C (PKC) was detected in protein extracts from mesophyll
      cell protoplasts (MCPs). It catalyzed the in vitro phosphorylation of the C1
      peptide PKC substrate and was markedly inhibited by a PKC-specific
      pseudosubstrate domain. However, it was only modestly activated by the
      phospholipids phosphatidylserine and lysophosphatidylcholine, while choline,
      oleyl acetylglycerol, phosphatidylinositol, and the phorbol ester phorbol 12
      myristate 13-acetate did not show any effect. Nevertheless, its activity was
      found to be associated with a polypeptide of 75kDa that was recognized by a PKC
      antibody raised against the C-terminus of rabbit PKCbeta II. In addition, this
      protein kinase was also inhibited by the Ca(2+)-dependent protein kinase
      (CDPK)/PKC inhibitors W7, H7, and staurosporine. Surprisingly, it was found to be
      phosphorylated in dark-adapted MCPs, albeit to a low extent, and this did not
      change during protoplast induction by light. W7, H7, and staurosporine were shown
      to markedly inhibit C(4)-PEPC phosphorylation in light-treated MCPs. These
      results support the view that this protein kinase is a good candidate to
      represent the Ca(2+)-activated component of the C(4)-PEPC phosphorylation
      cascade.

PMID- 14733925
TI  - Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin
      function and the pathogenesis of DFNA9.
AB  - The COCH gene mutated in DFNA9, an autosomal dominant hereditary sensorineural
      hearing loss and vestibular disorder, encodes Cochlin. Previously, we reported
      three bovine Cochlin isoforms, p63s, p44s, and p40s, which exhibit significant
      molecular heterogeneity in vivo. Here we have characterized Cochlin isoforms by
      generating four isoform-specific anti-Cochlin antibodies. The same three Cochlin
      isoforms, p63s, p44s, and p40s, were detected in human and cow inner ear tissue;
      however, p44s and p40s were not detected in perilymph. We identified a novel
      short 16kDa isoform in human perilymph and a 18-23kDa isoform in cow perilymph,
      named Cochlin-tomoprotein (CTP), corresponding to the N-terminus of full-length
      Cochlin (p63s) and the LCCL domain. Notably, CTP contains all of the known
      mutation sites associated with DFNA9. The pathogenesis of DFNA9 is not fully
      clarified as yet, and this novel perilymph-associated CTP isoform might provide
      mechanistic clues to how mutations in the COCH gene damage the inner ear
      function.

PMID- 14733926
TI  - ESR reveals the mobility of the neck linker in dimeric kinesin.
AB  - Conventional kinesin is a highly processive motor that converts the chemical
      energy of ATP hydrolysis into the unidirectional motility along microtubules. The
      processivity is thought to depend on the coordination between ATPase cycles of
      two motor domains and their neck linkers. Here we have used site-directed spin
      labeling electron spin resonance (SDSL-ESR) to determine the conformation of the
      neck linker in kinesin dimer in the presence and absence of microtubules. The
      spectra show that the neck linkers co-exist in both docked and disordered
      conformations, which is consistent with the results of monomeric kinesin. In all
      nucleotide states, however, the neck linkers are well ordered when dimeric
      kinesin is bound to the microtubule. This result suggests that the orientation of
      each neck linker that is fixed rigidly controls the kinesin motion along
      microtubule tracks.

PMID- 14733924
TI  - Characterization of Rad6 from a higher plant, rice (Oryza sativa L.) and its
      interaction with Sgt1, a subunit of the SCF ubiquitin ligase complex.
AB  - We report here the existence of interactions between a ubiquitin-conjugating
      enzyme, Rad6, from rice, Oryza sativa L. cv. Nipponbare (OsRad6), and Sgt1
      (OsSgt1), a novel subunit of the SCF ubiquitin ligase complex. Rad6 is not only
      related to post-replicational repair but also to the proteasome system, while
      Sgt1 has a function in kinetochore assembly. The relationship between the two is
      unexpected, but of great interest. The open reading frames of OsRad6 and OsSgt1
      encode predicted products of 152 and 367 amino acid residues, respectively, with
      molecular weights of 17.3 and 40.9kDa. Two-hybrid and pull-down analyses
      indicated that OsRad6 binds to OsSgt1, and transcripts of both OsRad6 and OsSgt1
      were found to be strongly expressed only in the proliferating tissues such as the
      shoot apical meristem, suggesting that their expression is cell cycle-dependent.
      The amount of the Rad6 mRNA in cultured cells increased rapidly after division
      was halted, and mRNA levels of Rad6 and Sgt1 were induced by UV- and DNA-damaging
      agents such as MMS or H(2)O(2). The Rad6 pathway for repair or the proteasome
      system may thus require Sgt1 as ubiquitin-conjugating enzyme.

PMID- 14733927
TI  - Hydrophobic effect of trityrosine on heme ligand exchange during folding of
      cytochrome c.
AB  - Effect of a hydrophobic peptide on folding of oxidized cytochrome c (cyt c) is
      studied with trityrosine. Folding of cyt c was initiated by pH jump from 2.3
      (acid-unfolded) to 4.2 (folded). The Soret band of the 2-ms transient absorption
      spectrum during folding decreased its intensity and red-shifted from 397 to 400
      nm by interaction with trityrosine, whereas tyrosinol caused no significant
      effect. The change in the transient absorption spectrum by interaction with
      trityrosine was similar to that obtained with 100 mM imidazole, which showed that
      the population of the intermediate His/His coordinated species increased during
      folding of cyt c by interaction with trityrosine. The absorption change was
      biphasic, the fast phase (82+/-9s(-1)) corresponding to the transition from the
      His/H(2)O to the His/Met coordinated species, whereas the slow phase (24+/-3s(
      1)) from His/His to His/Met. By addition of trityrosine, the relative ratio of
      the slow phase increased, due to increase of the His/His species at the initial
      stage of folding. According to the resonance Raman spectra of cyt c, the high
      spin 6-coordinate and low-spin 6-coordinate species were dominated at pH 2.3 and
      4.2, respectively, and these species were not affected by addition of
      trityrosine. These results demonstrated that the His/His species increased by
      interaction with trityrosine at the initial stage of cyt c folding, whereas the
      heme coordination structure was not affected by trityrosine when the protein was
      completely unfolded or folded. Hydrophobic peptides thus may be useful to study
      the effects of hydrophobic interactions on protein folding.

PMID- 14733928
TI  - Analysis of type I signal peptidase affinity and specificity for preprotein
      substrates.
AB  - Type I signal peptidases (SPases) are membrane-bound endopeptidases responsible
      for the catalytic cleavage of signal peptides from secretory proteins. Here, we
      analysed the interaction between a bacterial type I SPase and preprotein
      substrates using surface plasmon resonance. The use of a home-made biosensor
      surface based on a mixed self-assembled monolayer of thiols on gold allowed
      qualitative and kinetic analysis. In vitro binding of purified preproteins to a
      covalently immobilised bacterial SPase was found to be rather efficient (apparent
      K(D)=10(-7)-10(-8)M). The signal peptide was shown to be a prerequisite for SPase
      binding and the nature of the mature part of the preprotein significantly
      affected SPase binding affinity. The developed biosensor containing immobilised
      SPase is of great importance for analysis of specificity at substrate binding
      level and for drug screening. In fact, this is the first report of a membrane
      protein that was covalently attached to a biosensor surface and that retained
      binding capacity.